PMID- 26287250
TI  - Identification of Recurrence-Related microRNAs from Bone Marrow in Hepatocellular
      Carcinoma Patients.
AB  - Hepatocellular carcinoma (HCC) is a poor-prognosis cancer due to its high rate of
      recurrence. microRNAs (miRNAs) are a class of small non-coding RNA molecules that
      affect crucial processes in cancer development. The objective of this study is to
      identify the role of miRNAs in patient bone marrow (BM) and explore the function
      of these molecules during HCC progression. We purified miRNAs from bone marrow
      cells of seven HCC patients, and divided them into three fractions by cell
      surface markers as follows: CD14(+) (macrophage), CD14(-)/CD45(+) (lymphocyte),
      and CD14(-)/CD45(-)/EpCAM(+) (epithelial cell). We employed microarray-based
      profiling to analyze miRNA expression in the bone marrow of patients with HCC.
      Differentially expressed miRNAs were significantly different between fractions
      from whole bone marrow, macrophages, and lymphocytes, and depended on stages in
      tumor progression. Differences in expression of miRNAs associated with cell
      proliferation also varied significantly between HCC patients with recurrence,
      multiple tumors, and advanced clinical stages. These results suggest that miRNA
      profiles in separated fractions of BM cells are associated with HCC progression.

PMID- 26287252
TI  - Optical Microfibre Based Photonic Components and Their Applications in Label-Free
      Biosensing.
AB  - Optical microfibre photonic components offer a variety of enabling properties,
      including large evanescent fields, flexibility, configurability, high
      confinement, robustness and compactness. These unique features have been
      exploited in a range of applications such as telecommunication, sensing, optical
      manipulation and high Q resonators. Optical microfibre biosensors, as a class of
      fibre optic biosensors which rely on small geometries to expose the evanescent
      field to interact with samples, have been widely investigated. Due to their
      unique properties, such as fast response, functionalization, strong confinement,
      configurability, flexibility, compact size, low cost, robustness, ease of
      miniaturization, large evanescent field and label-free operation, optical
      microfibres based biosensors seem a promising alternative to traditional
      immunological methods for biomolecule measurements. Unlabeled DNA and protein
      targets can be detected by monitoring the changes of various optical transduction
      mechanisms, such as refractive index, absorption and surface plasmon resonance,
      since a target molecule is capable of binding to an immobilized optical
      microfibre. In this review, we critically summarize accomplishments of past
      optical microfibre label-free biosensors, identify areas for future research and
      provide a detailed account of the studies conducted to date for biomolecules
      detection using optical microfibres. 

PMID- 26287251
TI  - Exploring miRNA-Associated Signatures with Diagnostic Relevance in Glioblastoma
      Multiforme and Breast Cancer Patients.
AB  - The growing attention that non-coding RNAs have attracted in the field of cancer
      research in recent years is undeniable. Whether investigated as prospective
      therapeutic targets or prognostic indicators or diagnostic biomarkers, the
      clinical relevance of these molecules is starting to emerge. In addition,
      identification of non-coding RNAs in a plethora of body fluids has further
      positioned these molecules as attractive non-invasive biomarkers. This review
      will first provide an overview of the synthetic cascade that leads to the
      production of the small non-coding RNAs microRNAs (miRNAs) and presents their
      strengths as biomarkers of disease. Our interest will next be directed at
      exploring the diagnostic utility of miRNAs in two types of cancer: the brain
      tumor glioblastoma multiforme (GBM) and breast cancer. Finally, we will discuss
      additional clinical implications associated with miRNA detection as well as
      introduce other non-coding RNAs that have generated recent interest in the cancer
      research community. 

PMID- 26287253
TI  - Current and Prospective Methods for Plant Disease Detection.
AB  - Food losses due to crop infections from pathogens such as bacteria, viruses and
      fungi are persistent issues in agriculture for centuries across the globe. In
      order to minimize the disease induced damage in crops during growth, harvest and
      postharvest processing, as well as to maximize productivity and ensure
      agricultural sustainability, advanced disease detection and prevention in crops
      are imperative. This paper reviews the direct and indirect disease identification
      methods currently used in agriculture. Laboratory-based techniques such as
      polymerase chain reaction (PCR), immunofluorescence (IF), fluorescence in-situ
      hybridization (FISH), enzyme-linked immunosorbent assay (ELISA), flow cytometry
      (FCM) and gas chromatography-mass spectrometry (GC-MS) are some of the direct
      detection methods. Indirect methods include thermography, fluorescence imaging
      and hyperspectral techniques. Finally, the review also provides a comprehensive
      overview of biosensors based on highly selective bio-recognition elements such as
      enzyme, antibody, DNA/RNA and bacteriophage as a new tool for the early
      identification of crop diseases. 

PMID- 26287254
TI  - Point-of-Care Diagnostics in Low Resource Settings: Present Status and Future
      Role of Microfluidics.
AB  - The inability to diagnose numerous diseases rapidly is a significant cause of the
      disparity of deaths resulting from both communicable and non-communicable
      diseases in the developing world in comparison to the developed world. Existing
      diagnostic instrumentation usually requires sophisticated infrastructure, stable
      electrical power, expensive reagents, long assay times, and highly trained
      personnel which is not often available in limited resource settings. This review
      will critically survey and analyse the current lateral flow-based point-of-care
      (POC) technologies, which have made a major impact on diagnostic testing in
      developing countries over the last 50 years. The future of POC technologies
      including the applications of microfluidics, which allows miniaturisation and
      integration of complex functions that facilitate their usage in limited resource
      settings, is discussed The advantages offered by such systems, including low
      cost, ruggedness and the capacity to generate accurate and reliable results
      rapidly, are well suited to the clinical and social settings of the developing
      world. 

PMID- 26287255
TI  - Analysis of Metabolomics Datasets with High-Performance Computing and Metabolite
      Atlases.
AB  - Even with the widespread use of liquid chromatography mass spectrometry (LC/MS)
      based metabolomics, there are still a number of challenges facing this promising
      technique. Many, diverse experimental workflows exist; yet there is a lack of
      infrastructure and systems for tracking and sharing of information. Here, we
      describe the Metabolite Atlas framework and interface that provides highly
      efficient, web-based access to raw mass spectrometry data in concert with
      assertions about chemicals detected to help address some of these challenges.
      This integration, by design, enables experimentalists to explore their raw data,
      specify and refine features annotations such that they can be leveraged for
      future experiments. Fast queries of the data through the web using SciDB, a
      parallelized database for high performance computing, make this process operate
      quickly. By using scripting containers, such as IPython or Jupyter, to analyze
      the data, scientists can utilize a wide variety of freely available graphing,
      statistics, and information management resources. In addition, the interfaces
      facilitate integration with systems biology tools to ultimately link metabolomics
      data with biological models. 

PMID- 26287256
TI  - Mammalian Cell Surface Display as a Novel Method for Developing Engineered
      Lectins with Novel Characteristics.
AB  - Leguminous lectins have a conserved carbohydrate recognition site comprising four
      loops (A-D). Here, we randomly mutated the sequence and length of loops C and D
      of peanut agglutinin (PNA) and expressed the proteins on the surface of mouse
      green fluorescent protein (GFP)-reporter cells. Flow cytometry, limiting
      dilution, and cDNA cloning were used to screen for several mutated PNAs with
      distinct properties. The mutated PNA clones obtained using NeuAcalpha2-6(Galbeta1
      3)GalNAc as a ligand showed preference for NeuAcalpha2-6(Galbeta1-3)GalNAc rather
      than non-sialylated Galbeta1-3GlcNAc, whereas wild-type PNA binds to Galbeta1
      3GlcNAc but not sialylated Galbeta1-3GalNAc. Sequence analyses revealed that for
      all of the glycan-reactive mutated PNA clones, (i) loop C was eight amino acids
      in length, (ii) loop D was identical to that of wild-type PNA, (iii) residue 127
      was asparagine, (iv) residue 125 was tryptophan, and (v) residue 130 was
      hydrophobic tyrosine, phenylalanine, or histidine. The sugar-binding ability of
      wild-type PNA was increased nine-fold when Tyr125 was mutated to tryptophan, and
      that of mutated clone C was increased more than 30-fold after His130 was changed
      to tyrosine. These results provide an insight into the relationship between the
      amino acid sequences of the carbohydrate recognition site and sugar-binding
      abilities of leguminous lectins. 

PMID- 26287257
TI  - Chromatin Remodeling and Transcriptional Control in Innate Immunity: Emergence of
      Akirin2 as a Novel Player.
AB  - Transcriptional regulation of inflammatory gene expression has been at the
      forefront of studies of innate immunity and is coordinately regulated by
      transcription factors, including NF-kappaB, and chromatin modifiers. The growing
      evidence for involvement of chromatin in the regulation of gene expression in
      innate immune cells, has uncovered an evolutionarily conserved role of microbial
      sensing and chromatin remodeling. Toll-like receptors and RIG-I-like receptors
      trigger these signaling pathways leading to transcriptional expression of a set
      of genes involved in inflammation. Tightly regulated control of this gene
      expression is a paramount, and often foremost, goal of most biological endeavors.
      In this review, we will discuss the recent progress about the molecular
      mechanisms governing control of pro-inflammatory gene expression by an
      evolutionarily conserved novel nuclear protein Akirin2 in macrophages and its
      emergence as an essential link between NF-kappaB and chromatin remodelers for
      transcriptional regulation. 

PMID- 26287258
TI  - Toxic Oligomeric Alpha-Synuclein Variants Present in Human Parkinson's Disease
      Brains Are Differentially Generated in Mammalian Cell Models.
AB  - Misfolding and aggregation of alpha-synuclein into toxic soluble oligomeric alpha
      synuclein aggregates has been strongly correlated with the pathogenesis of
      Parkinson's disease (PD). Here, we show that two different morphologically
      distinct oligomeric alpha-synuclein aggregates are present in human post-mortem
      PD brain tissue and are responsible for the bulk of alpha-synuclein induced
      toxicity in brain homogenates from PD samples. Two antibody fragments that
      selectively bind the different oligomeric alpha-synuclein variants block this
      alpha-synuclein induced toxicity and are useful tools to probe how various cell
      models replicate the alpha-synuclein aggregation pattern of human PD brain. Using
      these reagents, we show that mammalian cell type strongly influences alpha
      synuclein aggregation, where neuronal cells best replicate the PD brain alpha
      synuclein aggregation profile. Overexpression of alpha-synuclein in the different
      cell lines increased protein aggregation but did not alter the morphology of the
      oligomeric aggregates generated. Differentiation of the neuronal cells into a
      cholinergic-like or dopaminergic-like phenotype increased the levels of
      oligomeric alpha-synuclein where the aggregates were localized in cell neurites
      and cell bodies. 

PMID- 26287259
TI  - Inhibition of Topoisomerase (DNA) I (TOP1): DNA Damage Repair and Anticancer
      Therapy.
AB  - Most chemotherapy regimens contain at least one DNA-damaging agent that
      preferentially affects the growth of cancer cells. This strategy takes advantage
      of the differences in cell proliferation between normal and cancer cells.
      Chemotherapeutic drugs are usually designed to target rapid-dividing cells
      because sustained proliferation is a common feature of cancer [1,2]. Rapid DNA
      replication is essential for highly proliferative cells, thus blocking of DNA
      replication will create numerous mutations and/or chromosome rearrangements
      ultimately triggering cell death [3]. Along these lines, DNA topoisomerase
      inhibitors are of great interest because they help to maintain strand breaks
      generated by topoisomerases during replication. In this article, we discuss the
      characteristics of topoisomerase (DNA) I (TOP1) and its inhibitors, as well as
      the underlying DNA repair pathways and the use of TOP1 inhibitors in cancer
      therapy. 

PMID- 26287260
TI  - Genome Instability in Development and Aging: Insights from Nucleotide Excision
      Repair in Humans, Mice, and Worms.
AB  - DNA damage causally contributes to aging and cancer. Congenital defects in
      nucleotide excision repair (NER) lead to distinct cancer-prone and premature
      aging syndromes. The genetics of NER mutations have provided important insights
      into the distinct consequences of genome instability. Recent work in mice and C.
      elegans has shed new light on the mechanisms through which developing and aging
      animals respond to persistent DNA damage. The various NER mouse mutants have
      served as important disease models for Xeroderma pigmentosum (XP), Cockayne
      syndrome (CS), and trichothiodystrophy (TTD), while the traceable genetics of C.
      elegans have allowed the mechanistic delineation of the distinct outcomes of
      genome instability in metazoan development and aging. Intriguingly, highly
      conserved longevity assurance mechanisms respond to transcription-blocking DNA
      lesions in mammals as well as in worms and counteract the detrimental
      consequences of persistent DNA damage. The insulin-like growth factor signaling
      (IIS) effector transcription factor DAF-16 could indeed overcome DNA damage
      driven developmental growth delay and functional deterioration even when DNA
      damage persists. Longevity assurance mechanisms might thus delay DNA damage
      driven aging by raising the threshold when accumulating DNA damage becomes
      detrimental for physiological tissue functioning. 

PMID- 26287262
TI  - A multi-stimuli responsive, self-assembling, boronic acid dipeptide.
AB  - Modification of the dipeptide of phenylalanine, FF, with a boronic acid (BA)
      functionality imparts unique aqueous self-assembly behavior that responds to
      multiple stimuli. Changes in pH and ionic strength are used to trigger
      hydrogelation via the formation of nanoribbon networks. Furthermore, we show for
      the first time that the binding of polyols to the BA functionality can modulate a
      peptide between its assembled and disassembled states. 

PMID- 26287263
TI  - Relationship between annular tear and presence of Propionibacterium acnes in
      lumbar intervertebral disc.
AB  - PURPOSE: Propionibacterium acnes (P. acnes) in the intervertebral disc may result
      in low back pain. The purpose of this study was to determine how P. acnes
      accesses the disc. METHODS: Patients with low back pain and/or sciatica were
      examined using X-ray and MRI before surgery. The intervertebral disc space height
      was measured on X-ray image. Disc and muscle samples were obtained from 46
      patients undergoing discectomy at the lumbar spine. The tear of annulus was
      inspected before discectomy. In the disc and muscle tissue cultures, 16S rDNA
      gene specific for P. acnes was examined using PCR. RESULTS: The discs from 11
      (23.9 %) patients were identified as 16S rDNA positive, in which two patients
      also had 16S rDNA in their muscles. 16S rDNA gene was significantly more likely
      to appear in the discs with annular tear than those without tear (P < 0.05). The
      disc space height was significantly decreased when the disc contained P. acnes.
      CONCLUSION: P. acnes is significantly more likely to be present in herniated
      discs with an annular tear than in herniated discs without such a tear. Since in
      the vast majority of these cases, no P. acnes was found in control muscle
      samples, a true infection with P. acnes is far more likely than a contamination.

PMID- 26287264
TI  - Attention problems in very preterm children from childhood to adulthood: the
      Bavarian Longitudinal Study.
AB  - BACKGROUND: Very preterm (VP; gestational age <32 weeks) and very low birth
      weight (VLBW; <1500 grams) is related to attention problems in childhood and
      adulthood. The stability of these problems into adulthood is not known. METHODS:
      The Bavarian Longitudinal Study is a prospective cohort study that followed 260
      VP/VLBW and 229 term-born individuals from birth to adulthood. Data on attention
      were collected at 6, 8, and 26 years of age, using parent reports, expert
      behavior observations, and clinical ADHD diagnoses. RESULTS: At each assessment,
      VP/VLBW individuals had significantly more attention problems, shorter attention
      span, and were more frequently diagnosed with ADHD than term-born comparisons. In
      both VP/VLBW and term-born individuals, overall, attention span increased and
      attention problems decreased from childhood to adulthood. Attention problems and
      attention span were more stable over time for VP/VLBW than term-born individuals.
      Similarly, ADHD diagnoses showed moderate stability from childhood to adulthood
      in VP/VLBW, but not in term-born individuals. However, when those with severe
      disabilities were excluded, differences between VP/VLBW and term-born individuals
      reduced. CONCLUSIONS: Despite improvement in attention regulation from childhood
      to adulthood, children born very preterm remained at increased risk for attention
      problems in adulthood. In contrast, term-born children with clinical attention
      problems outgrew these by adulthood. As inattentive behavior of VP/VLBW children
      may be overlooked by teachers, it may be necessary to raise awareness for school
      intervention programs that reduce attention problems in VP/VLBW children.

PMID- 26287261
TI  - Oxidative Stress and Maxi Calcium-Activated Potassium (BK) Channels.
AB  - All cells contain ion channels in their outer (plasma) and inner (organelle)
      membranes. Ion channels, similar to other proteins, are targets of oxidative
      impact, which modulates ion fluxes across membranes. Subsequently, these ion
      currents affect electrical excitability, such as action potential discharge (in
      neurons, muscle, and receptor cells), alteration of the membrane resting
      potential, synaptic transmission, hormone secretion, muscle contraction or
      coordination of the cell cycle. In this chapter we summarize effects of oxidative
      stress and redox mechanisms on some ion channels, in particular on maxi calcium
      activated potassium (BK) channels which play an outstanding role in a plethora of
      physiological and pathophysiological functions in almost all cells and tissues.
      We first elaborate on some general features of ion channel structure and function
      and then summarize effects of oxidative alterations of ion channels and their
      functional consequences. 

PMID- 26287265
TI  - Factors that influence the suitability of human organ-cultured corneas.
AB  - PURPOSE: The purpose was to assess the influence of donor and storage factors on
      the suitability of organ-cultured corneas for transplantation. METHODS: Data from
      1340 donor corneas stored between 2009 and 2015 were analyzed retrospectively.
      Logistic regression analysis was used to assess the influence of different
      factors on the suitability of grafts for transplantation. RESULTS: Forty-one
      percent (553/1340) of corneas were discarded. The leading causes were medical
      contraindication (20.2 %) and poor endothelial quality (19.3 %). Donor age
      influenced suitability for transplantation significantly. Corneas from donors
      aged 80 years and older were more likely to be discarded because of endothelial
      insufficiency (P < 0.0001). The cause of donor death including infection and
      multiple organ dsyfunction syndrom (MODS) increased the risk of bacterial or
      fungal contamination during organ culture (P = 0.007 and P = 0.014,
      respectively). Prolonged time between death and enucleation was associated with
      an increased risk of unsuitability for transplantation (P < 0.0001). The amount
      of time between death and corneoscleral disc excision and duration of storage
      influenced the suitability for transplantation (P = 0.0007 and P < 0.0001,
      respectively). CONCLUSION: Donor age, cause of death, storage time, death to
      enucleation and death to disc excision times influenced transplantation
      suitability. The percentage of discarded corneas may be reduced by shortening
      storage time, death to enucleation, and death to corneoscleral disc excision
      times. Setting a maximum donor age could reduce the percentage of discarded
      corneas. However, as long as there is a lack of donor corneas, we do not
      recommend any donor age limit.

PMID- 26287266
TI  - Spatial and temporal analyses of posture in strabismic children.
AB  - PURPOSE: To analyse postural performances of strabismic children, both in the
      spatial and the temporal domains, by wavelet transformation, comparing both
      stable and unstable situations. METHODS: Twenty-six strabismic children aged from
      4 to 11 years old and 26 age-matched normal children participated in the study.
      Postural performances were evaluated using the Framiral(r) platform. Posture was
      recorded in the following conditions: eyes open fixating a target and eyes closed
      on stable and unstable platforms. RESULTS: For both strabismic and non-strabismic
      children, the surface and the mean velocity of the center of pressure (CoP) were
      significantly larger in the eyes closed on unstable platform condition, but this
      was much more pronounced in case of strabismus. Spectral power index and
      cancelling time were also found to be altered in strabismic children compared to
      non-strabismic children. CONCLUSIONS: This data demonstrates poor postural
      stability for both groups on an unstable platform with the eyes closed. However,
      strabismic children had significantly worse performance than non-strabismic
      children. Strabismic children also engage more energy to stabilize their posture
      by using visuo-vestibular sensory inputs to compensate their altered vision due
      to strabismus, in comparison to non-strabismic children.

PMID- 26287267
TI  - GLP-1 Receptor Agonist Exenatide Attenuates the Detrimental Effects of Obesity on
      Inflammatory Profile in Testis and Sperm Quality in Mice.
AB  - PROBLEM: Male obesity has been linked to subfecundity. This study is to
      investigate the effects of GLP-1 receptor (GLP-1R) agonist exenatide on sperm
      quality in high-fat diet (HFD)-induced obese mice. METHOD OF STUDY: After 12
      weeks of chow diet (CD) or HFD challenge, mice on HFD were allocated to either
      saline or exenatide (24 nmol/kg/day) interventions for 8 weeks. Sperm quality and
      the inflammatory profile of testis were compared among three groups. RESULTS:
      Obesity reduced the quality of sperm and changed the inflammatory profile
      characterized by increased mRNA expression levels of TNF-alpha, MCP-1, and F4/80
      in testis. Exenatide intervention reduced the expression of pro-inflammatory
      cytokines and improved the quality of sperm. CONCLUSION: HFD-induced obesity
      leads to the impairment of sperm quality and increased inflammation of testis in
      mice, and the abnormal physiology can be attenuated by exenatide treatment.
      Exenatide treatment may bring additional profits to obese and diabetes men by
      improving sperm function.

PMID- 26287268
TI  - Unskilled unawareness and the learning curve in robotic spine surgery.
AB  - BACKGROUND: Robotic assistance for the placement of pedicle screws has been
      established as a safe technique. Nonetheless rare instances of screw misplacement
      have been reported.The aim of the present retrospective study is to assess
      whether experience and time affect the accuracy of screws placed with the help of
      the SpineAssistTM robot system. METHODS: Postoperative computed tomography (CT)
      scans of 258 patients requiring thoracolumbar pedicle screw instrumentation from
      2008 to 2013 were reviewed. Overall, 13 surgeons performed the surgeries. A
      pedicle breach of >3 mm was graded as a misplacement. Surgeons were dichotomised
      into an early and experienced period in increments of five surgeries. RESULTS: In
      258 surgeries, 1,265 pedicle screws were placed with the aid of the robot system.
      Overall, 1,217 screws (96.2 %) were graded as acceptable. When displayed by
      surgeon, the development of percent misplacement rates peaked between 5 and 25
      surgeries in 12 of 13 surgeons. The overall misplacement rate in the first five
      surgeries was 2.4 % (6/245). The misplacement rate rose to 6.3 % between 11 and
      15 surgeries (10/158; p = 0.20), and reached a significant peak between 16 and 20
      surgeries with a rate of 7.1 % (8/112; p = 0.03). Afterwards, misplacement rates
      declined. CONCLUSIONS: A major peak in screw inaccuracies occurred between cases
      10 and 20, and a second, smaller one at about 40 surgeries. One potential
      explanation could be a transition from decreased supervision (unskilled but
      aware) to increased confidence of a surgeon (unskilled but unaware) who adopts
      this new technique prior to mastering it (skilled). We therefore advocate
      ensuring competent supervision for new surgeons at least during the first 25
      procedures of robotic spine surgery to optimise the accuracy of robot-assisted
      pedicle screws.

PMID- 26287269
TI  - Factors influencing the growth rate of vestibular schwannoma in patients with
      neurofibromatosis type 2.
AB  - BACKGROUND: Neurofibromatosis type 2 (NF2) is a devastating disease with no well
      accepted management guidelines. Better understanding of the disease process
      provides the basis for how or when to initiate treatment. Only few studies have
      addressed the factors influencing the growth rate of NF2-related vestibular
      schwannomas (VSs), and these studies have reported variable results. This study
      aimed to assess the clinical factors influencing the growth rate of NF2-related
      VSs. METHODS: The medical records of 66 patients (totalling 74 VSs) were
      retrospectively analysed. The tumours were measured according to a two-component
      box model. The tumour growth rate was estimated by linear regression analysis of
      the changes in VS volumes over time. The clinical characteristics of all the
      patients were recorded. The relationship between the tumour growth rate and
      clinical factors were analysed. Linear regression, Pearson's correlation and
      Student's t-test were conducted using the SPSS 19.0 statistical package. RESULTS:
      The median follow-up duration was 4.9 years. The VSs growth rate was highly
      correlated with the initial VS volume (r = 0.97, p < 0.01). However, it was
      inversely correlated with the age at symptom onset (r = -0.41, p < 0.01). The
      average VS growth rate in patients with spinal tumours was 13.18 cm(3)/year
      compared with 0.19 cm(3)/year in patients without spinal tumours (p < 0.01). The
      VS growth rate in patients who had resection of a contralateral VS was slightly
      higher than that of patients with untreated VSs (p < 0.01). Other factors
      including sex, vestibular symptom, presence of other cranial schwannomas, family
      history and dermal abnormalities did not affect the VS growth rate. CONCLUSIONS:
      The potential clinical factors influencing the VS growth rate are the age at
      symptom onset, initial tumour volume and presence of spinal tumours. Surgical
      resection of VSs might accelerate the growth rate of contralateral tumours. The
      effects of these factors require further experimental confirmation.

PMID- 26287270
TI  - A new species of Centromochlus (Siluriformes, Auchenipteridae, Centromochlinae)
      from the middle Rio Tocantins basin, Brazil.
AB  - A new species of the catfish genus Centromochlus (Auchenipteridae,
      Centromochlinae) is described. The new species is diagnosed by having numerous
      dark rounded blotches over the body and fins, dorsal-fin spine with serrations
      anteriorly and smooth posteriorly, anal fin of mature males with three unbranched
      and seven branched rays, anterior nuchal plate absent and posterior nuchal plate
      not extended ventrally. The new species is described from a small stream in the
      Estacao Ecologica Serra Geral de Tocantins, a natural reserve in the centre of
      the Brazilian Cerrado, close to the watershed between the Rio Tocantins and the
      Rio Sao Francisco basins. The new species is possibly the sister taxon to the
      recently described Centromochlus meridionalis from the upper Rio Tapajos. Those
      two species share with Centromochlus perugiae, from the upper Amazon and upper
      Paraguay, derived features associated with the modified anal fin in sexually
      mature males. 

PMID- 26287271
TI  - Design, Synthesis, and Evaluation of an (18)F-Labeled Radiotracer Based on
      Celecoxib-NBD for Positron Emission Tomography (PET) Imaging of Cyclooxygenase-2
      (COX-2).
AB  - A series of novel fluorine-containing cyclooxygenase-2 (COX-2) inhibitors was
      designed and synthesized based on the previously reported fluorescent COX-2
      imaging agent celecoxib-NBD (3; NBD=7-nitrobenzofurazan). In vitro COX-1/COX-2
      inhibitory data show that N-(4-fluorobenzyl)-4-(5-p-tolyl-3
      trifluoromethylpyrazol-1-yl)benzenesulfonamide (5; IC50 =0.36 MUM, SI>277) and N
      fluoromethyl-4-(5-p-tolyl-3-trifluoromethylpyrazol-1-yl)benzenesulfonamide (6;
      IC50 =0.24 MUM, SI>416) are potent and selective COX-2 inhibitors. Compound 5 was
      selected for radiolabeling with the short-lived positron emitter fluorine-18
      ((18) F) and evaluated as a positron emission tomography (PET) imaging agent.
      Radiotracer [(18) F]5 was analyzed in vitro and in vivo using human colorectal
      cancer model HCA-7. Although radiotracer uptake into COX-2-expressing HCA-7 cells
      was high, no evidence for COX-2-specific binding was found. Radiotracer uptake
      into HCA-7 tumors in vivo was low and similar to that of muscle, used as
      reference tissue. 

PMID- 26287273
TI  - [Differential diagnosis of a narrow QRS tachycardia].
AB  - The differential diagnosis of a narrow QRS tachycardia requires on the one hand
      knowledge about the clinical data of the tachycardia patient but on the other
      hand a systematic step by step analysis of the electrocardiogram (ECG) is the
      most successful approach. Apart from the question of regularity or irregularity
      of the QRS complexes, the presence and detection of P waves is also of
      importance. The P wave timing in relation to the preceding and the following QRS
      complexes as well as the numerical relationship of P waves and QRS complexes
      allow a well-founded suspected diagnosis to be achieved in most cases. Even the
      differentiation between atrioventricular (AV) nodal reentrant tachycardia (AVNRT)
      versus orthodromic AV reentrant tachycardia (AVRT), e.g. by accessory leads, is
      in most cases possible in a surface ECG. Obviously, there are constellations
      which need an invasive electrophysiological procedure for a definitive diagnosis.

PMID- 26287272
TI  - Hypothermic Preconditioning of Human Cortical Neurons Requires Proteostatic
      Priming.
AB  - Hypothermia is potently neuroprotective but poor mechanistic understanding has
      restricted its clinical use. Rodent studies indicate that hypothermia can elicit
      preconditioning, wherein a subtoxic cellular stress confers resistance to an
      otherwise lethal injury. The molecular basis of this preconditioning remains
      obscure. Here we explore molecular effects of cooling using functional cortical
      neurons differentiated from human pluripotent stem cells (hCNs). Mild-to-moderate
      hypothermia (28-32  degrees C) induces cold-shock protein expression and mild
      endoplasmic reticulum (ER) stress in hCNs, with full activation of the unfolded
      protein response (UPR). Chemical block of a principal UPR pathway mitigates the
      protective effect of cooling against oxidative stress, whilst pre-cooling neurons
      abrogates the toxic injury produced by the ER stressor tunicamycin. Cold-stress
      thus preconditions neurons by upregulating adaptive chaperone-driven pathways of
      the UPR in a manner that precipitates ER-hormesis. Our findings establish a novel
      arm of neurocryobiology that could reveal multiple therapeutic targets for acute
      and chronic neuronal injury. 

PMID- 26287274
TI  - The positive impact of structured teaching in the operating room.
AB  - BACKGROUND: A survey of obstetric and gynaecology trainees in Australia found the
      trainee's opinion of the consultants' teaching ability for laparoscopic
      procedures and procedures dealing with complications as 'poor' in 21.2% and 23.4%
      of responses, respectively (Aust NZ J Obstet Gynaecol 2009; 49: 84). Surgical
      caseload per trainee is falling for a variety of reasons. Strategies need to be
      adopted to enhance the surgical learning experience of trainees in the operating
      room. AIMS: We describe the use of a structured encounter template to facilitate
      the teaching of surgery in the operating room and report the response of the
      trainees to this intervention. METHODS: Trainees attached to a gynaecologic
      surgery unit all underwent surgical training using a set format based on the
      surgical encounter template, including briefing, goal setting and intra-operative
      teaching aims as well as debriefing. Data on the trainees' experience and
      perception of their learning experience were then collected and analysed as
      quantitative and qualitative data sets. RESULTS: The trainees reported
      satisfaction with the use of a structured encounter template to facilitate the
      surgical teaching in the operating room. Some trainees had not received such
      clarity of feedback or the opportunity to complete a procedure independently
      prior to using the structured encounter template. CONCLUSIONS: A structured
      surgical encounter template based on andragogy principles to focus consultant
      teaching in the operating room is highly acceptable to obstetric and gynaecology
      trainees in Australia. Allowing the trainee the opportunity to set objectives and
      receive feedback empowers the trainee and enhances their educational experience.

PMID- 26287275
TI  - Therapy of Liver Abscesses.
AB  - BACKGROUND: Liver abscess (LA) is an uncommon but potentially life-threatening
      disease with significant morbidity and mortality. METHODS: This review
      comprehensively describes epidemiology, pathogenesis, diagnosis, and treatment of
      LA, with a strong focus on antimicrobial treatment choices and the impact of
      multidrug-resistant pathogens. RESULTS: In industrialized areas, pyogenic liver
      abscess (PLA) accounts for over 80% of the cases, whereas Entamoeba histolyticais
      responsible for up to 10% of the cases, with a higher incidence in tropical
      areas. Highly virulent strains of Klebsiella pneumoniaehave emerged as a
      predominant cause of PLA in Asian countries and tend to spread to the USA,
      Australia, and European countries, therefore requiring special alertness. Most
      common symptoms of LA are fever, chills, and right upper quadrant abdominal pain,
      although a broad spectrum of non-specific symptoms may also occur. CONCLUSION:
      Imaging studies (ultrasound, computed tomography scan) and microbiological
      findings play a crucial role in the diagnosis of LA. The treatment of choice for
      PLA is a multimodal approach combining broad-spectrum antibiotics and aspiration
      or drainage of larger abscess cavities. Amebic LA can be cured by metronidazole
      therapy without drainage.

PMID- 26287276
TI  - Multiple myeloma: New surface antigens for the characterization of plasma cells
      in the era of novel agents.
AB  - BACKGROUND: Multiple Myeloma (MM) is a neoplastic disorder characterized by
      clonal proliferation of malignant plasma cells (PCs). Flow cytometry is an
      essential tool to confirm diagnosis and evaluate minimal residual disease (MRD).
      This study aims at identifying new surface PC markers suitable for targeted
      therapy in MM and able to improve MRD detection. METHODS: The expression of 82
      molecules provided by the "Ninth International Workshop on Leukocyte Antigens"
      was analyzed by flow cytometry in 5 MM cell lines and in 20 newly diagnosed MM
      (NDMM) patients. Based on the antigens expression and monoclonal antibody
      availability, CD150, CD48, CD229, CD352, CD319, CD272, CD86, CD200 and CD184 were
      subsequently tested in 24 NDMM, 8 relapsed MM (RMM), 6 plasma cell leukemia (PCL)
      and 13 healthy subjects. RESULTS: CD352 was less frequently expressed on NDMM
      than on healthy PCs; CD200 was more frequently expressed on NDMM than on RMM and
      healthy PCs. CD150, CD319, CD229, CD352 Mean Fluorescence Intensity (MFI) was
      lower in pathological than in healthy samples. The proportion of CD150-positive
      samples was lower in NDMM and RMM than in healthy subjects; CD86+ samples were
      less frequent in NDMM than in healthy subjects; CD200+ samples were more frequent
      in NDMM than in RMM and healthy subjects. CONCLUSIONS: CD150, CD86 and CD200 can
      help to identify malignant PCs; CD272, CD319, CD229, CD48 are highly expressed on
      all PCs and could be considered for targeted therapy. All these antigens could be
      added to a routine panel for PCs identification and MRD evaluation.

PMID- 26287277
TI  - Myosin Binding Protein-C Slow Phosphorylation is Altered in Duchenne Dystrophy
      and Arthrogryposis Myopathy in Fast-Twitch Skeletal Muscles.
AB  - Myosin Binding Protein-C slow (sMyBP-C), encoded by MYBPC1, comprises a family of
      regulatory proteins of skeletal muscles that are phosphorylated by PKA and PKC.
      MYBPC1 missense mutations are linked to the development of Distal Arthrogryposis
      1 (DA-1). Although structure-function details for this myopathy are evolving,
      function is undoubtedly driven by sequence variations and post-translational
      modifications in sMyBP-C. Herein, we examined the phosphorylation profile of
      sMyBP-C in mouse and human fast-twitch skeletal muscles. We used Flexor Digitorum
      Brevis (FDB) isolated from young (~2-months old) and old (~14-months old) wild
      type and mdx mice, and human Abductor Hallucis (AH) and gastrocnemious muscles
      carrying the DA-1 mutations. Our results indicate both constitutive and
      differential phosphorylation of sMyBP-C in aged and diseased muscles. We report a
      7-35% reduction in the phosphorylation levels of select sites in old wild type
      and young or old mdx FDB mouse muscles, compared to young wild type tissue.
      Similarly, we observe a 30-70% decrease in the phosphorylation levels of all PKA
      and PKC phospho-sites in the DA-1 AH, but not gastrocnemius, muscle. Overall, our
      studies show that the phosphorylation pattern of sMyBP-C is differentially
      regulated in response to age and disease, suggesting that phosphorylation plays
      important roles in these processes. 

PMID- 26287278
TI  - Evaluation of baseline corrected QT interval and azithromycin prescriptions in an
      academic medical center.
AB  - BACKGROUND: Azithromycin is used in the inpatient setting for a variety of
      conditions. In 2013, the US Food and Drug Administration released a warning
      regarding risk for corrected QT (QTc) prolongation and subsequent arrhythmias.
      Knowledge of inpatient prescribing patterns of QTc prolonging medications with
      respect to patient risk factors for adverse cardiovascular events can help
      recognize safe use in light of these new warnings. OBJECTIVE: To assess inpatient
      prescribing patterns, risk factors for QTc prolongation, and relationship between
      drug-drug interactions and cardiac monitoring in patients receiving azithromycin.
      DESIGN: Retrospective cohort study. PARTICIPANTS: One hundred inpatients >= 19
      years of age were randomly selected from 1610 patient encounters between October
      2012 and April 2013 who were administered at least 1 dose of azithromycin.
      MEASUREMENTS: Length of stay, reason for use, therapy duration, and concomitant
      medications were recorded. Telemetry charges and baseline electrocardiogram (ECG)
      prior to administration were assessed. RESULTS: Seventy-nine percent of
      azithromycin use was empiric. Sixty-five percent of patients received a baseline
      ECG prior to prescribing azithromycin, of which 60% had borderline or abnormal
      QTc prolongation. Seventy-six percent of patients were prescribed 2 or more QTc
      prolonging medications, of which there were more abnormal ECGs at baseline (P =
      0.03) despite having telemetry ordered less than half of the time. CONCLUSIONS:
      In a cohort of hospitalized patients, azithromycin was prescribed despite risk
      factors for QTc prolongation and administration of interacting medications.
      Selection of azithromycin by providers appears to be independent from these risk
      factors, and education and vigilance to drug-drug interactions may be useful in
      limiting cardiac events with prescribing azithromycin.

PMID- 26287279
TI  - The luminescence properties of heteroleptic [OsCl(CO)(N?N)(P?P)](+) complexes -
      radiative and non-radiative deactivation of the excited (3)*MLCT state.
AB  - The luminescence properties of the heteroleptic [OsCl(CO)(N?N)(P?P)](+) complexes
      with bidentate phosphine P?P and diimine N?N ligands have been studied in
      acetonitrile solutions at room temperature and in methanol/ethanol (1 : 1)
      glasses at 77 K. At room temperature the investigated complexes feature strong
      (with the quantum yields phiem from 0.17 up to 0.64), long-lived (with lifetimes
      tauem in the range of 1.5-44.2 MUs) (3)*MLCT emission. Analysis of (3)*MLCT
      emission band shapes leads to the quantities relevant for the radiative electron
      transfer (between the Os(2+) central ion and the N?N ligand) in the Marcus
      inverted region. It is also demonstrated that radiative kr and non-radiative knr
      decay rate constants of the excited (3)*MLCT states can be interpreted within the
      Mulliken-Hush formalism. Especially values of knr rate constants can be predicted
      using the parameters available from the analysis of the radiative (1)*MLCT <- S0
      and (3)*MLCT -> S0 charge transfer processes. 

PMID- 26287280
TI  - A new non-invasive method of infant spirometry demonstrates a level of
      repeatability that is comparable to traditional methods.
AB  - AIM: The FloRight system provides novel non-invasive infant spirometry based on
      electromagnetic inductance plethysmography. We investigated the consistency of
      repeated measurements carried out in a Norwegian neonatal intensive care unit
      (NICU) using the system and how well these were tolerated. METHODS: Tidal flow
      volume loops were obtained from 10 preterm infants at discharge, 10 stable
      growing preterm infants weighing about 1500 g and 10 term-born infants. A nurse
      experienced with the system measured all patients before and after meals, and
      these measurements were repeated by nurses new to the system. RESULTS: The
      measurements were well tolerated by the infants. The repeatability for the two
      parameters 'tidal volume' (Vt) and 'time to peak tidal expiratory flow to total
      expiratory time' (Tptef/Te) were relatively poor, similar to previous methods.
      However, the repeatability was good for the new 'flow-volume gravity mid-point'
      (FVg) parameter. Repeatability was better for term than preterm infants, when
      measurements were obtained by the experienced nurse and for measurements carried
      out before meals. CONCLUSION: The FloRight system proved feasible in a NICU
      setting. The repeatability of the lung function measurements was similar to those
      reported for traditional infant spirometry. The nurse's experience and the
      relationship to meals appeared to be important.

PMID- 26287281
TI  - Cultivating the uncultured: growing the recalcitrant cluster-2 Frankia strains.
AB  - The repeated failures reported in cultivating some microbial lineages are a major
      challenge in microbial ecology and probably linked, in the case of Frankia
      microsymbionts to atypical patterns of auxotrophy. Comparative genomics of the so
      far uncultured cluster-2 Candidatus Frankia datiscae Dg1, with cultivated
      Frankiae has revealed genome reduction, but no obvious physiological impairments.
      A direct physiological assay on nodule tissues from Coriaria myrtifolia infected
      with a closely-related strain permitted the identification of a requirement for
      alkaline conditions. A high pH growth medium permitted the recovery of a slow
      growing actinobacterium. The strain obtained, called BMG5.1, has short hyphae,
      produced diazovesicles in nitrogen-free media, and fulfilled Koch's postulates by
      inducing effective nodules on axenically grown Coriaria spp. and Datisca
      glomerata. Analysis of the draft genome confirmed its close proximity to the
      Candidatus Frankia datiscae Dg1 genome with the absence of 38 genes (trehalose
      synthase, fumarylacetoacetase, etc) in BMG5.1 and the presence of 77 other genes
      (CRISPR, lanthionine synthase, glutathione synthetase, catalase, Na+/H+
      antiporter, etc) not found in Dg1. A multi-gene phylogeny placed the two cluster
      2 strains together at the root of the Frankia radiation. 

PMID- 26287282
TI  - Biomarker development, from bench to bedside.
AB  - This review describes studies performed by our group and other laboratories in
      the field aimed at development of biomarkers not only for cancer but also for
      other diseases. The markers covered include tumor-associated trypsin inhibitor
      (TATI), tumor-associated trypsin (TAT), human chorionic gonadotropin (hCG),
      prostate-specific antigen (PSA) and their various molecular forms, their biology
      and diagnostic use. The discovery of TATI was the result of a hypothesis-driven
      project aimed at finding new biomarkers for ovarian cancer among urinary
      peptides. TATI has since proved to be a useful prognostic marker for several
      cancers. Recently, it has been named Serine Peptidase Inhibitor Kazal Type 1
      (SPINK1) after being rediscovered by several groups as a tumor-associated peptide
      by gene expression profiling and proteomic techniques and shown to promote tumor
      development by stimulating the EGF receptor. To explain why a trypsin inhibitor
      is strongly expressed in some cancers, research focused on the protease that it
      inhibited led to the finding of tumor-associated trypsin (TAT). Elevated serum
      concentrations of TAT-2 were found in some cancer types, but fairly high
      background levels of pancreatic trypsinogen-2 limited the use of TAT-2 for cancer
      diagnostics. However, trypsinogen-2 and its complex with alpha1-protease
      inhibitor proved to be very sensitive and specific markers for pancreatitis.
      Studies on hCG were initiated by the need to develop more rapid and sensitive
      pregnancy tests. These studies showed that serum from men and non-pregnant women
      contains measurable concentrations of hCG derived from the pituitary. Subsequent
      development of assays for the subunits of hCG showed that the beta subunit of hCG
      (hCGbeta) is expressed at low concentrations by most cancers and that it is a
      strong prognostic marker. These studies led to the formation of a working group
      for standardization of hCG determinations and the development of new reference
      reagents for several molecular forms of hCG. The preparation of intact hCG has
      been adopted as the fifth international standard by WHO. Availability of several
      well-defined forms of hCG made it possible to characterize the epitopes of nearly
      100 monoclonal antibodies. This will facilitate design of immunoassays with pre
      defined specificity. Finally, the discovery of different forms of immunoreactive
      PSA in serum from a prostate cancer patient led to identification of the complex
      between PSA and alpha1-antichymotrypsin, and the use of assays for free and total
      PSA in serum for improved diagnosis of prostate cancer. Epitope mapping of PSA
      antibodies and establishment of PSA standards has facilitated establishment well
      standardized assays for the various forms of PSA. 

PMID- 26287283
TI  - Challenges in aromaticity: 150 years after Kekule's benzene.

PMID- 26287284
TI  - Individual- and Structural-Level Risk Factors for Suicide Attempts Among
      Transgender Adults.
AB  - This study assessed individual (ie, internalized transphobia) and structural
      forms of stigma as risk factors for suicide attempts among transgender adults.
      Internalized transphobia was assessed through a 26-item scale including four
      dimensions: pride, passing, alienation, and shame. State-level structural stigma
      was operationalized as a composite index, including density of same-sex couples;
      proportion of Gay-Straight Alliances per public high school; 5 policies related
      to sexual orientation discrimination; and aggregated public opinion toward
      homosexuality. Multivariable logistic generalized estimating equation models
      assessed associations of interest among an online sample of transgender adults (N
      = 1,229) representing 48 states and the District of Columbia. Lower levels of
      structural stigma were associated with fewer lifetime suicide attempts (AOR 0.96,
      95% CI 0.92-0.997), and a higher score on the internalized transphobia scale was
      associated with greater lifetime suicide attempts (AOR 1.18, 95% CI 1.04-1.33).
      Addressing stigma at multiple levels is necessary to reduce the vulnerability of
      suicide attempts among transgender adults. 

PMID- 26287285
TI  - Brain volume and white matter in youth with type 2 diabetes compared to obese and
      normal weight, non-diabetic peers: A pilot study.
AB  - Type 2 Diabetes Mellitus (T2DM) and obesity are linked to specific patterns of
      subcortical brain atrophy and decreased microstructural integrity of white
      matter. Fifteen adolescents (12-21-years-old, 80% Caucasian, 15% African
      American, mean BMI=32)-five with T2DM confirmed by oral glucose tolerance test,
      five matched obese adolescent controls without diabetes (OBCN), and five matched
      (race, sex) normal-weight controls (NWCN)-underwent Magnetic Resonance Imaging
      (MRI) for the collection of gray matter volume and white matter integrity.
      Analyses of Variance (ANOVAs) of the neuroimaging data revealed significant
      differences in caudate nucleus volume [F(2,12)=7.79, p<0.05] such that the normal
      weight group had significantly greater volume than the obese and T2DM groups
      (NWCN>OBCN, p=0.020; OBCN>T2DM, p=0.042; and NWCN>T2DM; p=0.003) after
      controlling for participant Body Mass Index (BMI). Similarly, there was a main
      effect for the volume of the thalamus [F(2,12)=4.39, p<0.05] with greater volume
      for both the NWC and the OBC groups in comparison to the T2DM group (NWC>T2DM,
      p=0.020; OBC>T2DM; p=0.040). Finally, an examination of white matter integrity
      among the three groups illustrated a pattern of white matter integrity reduction
      between normal-weight participants and both obese controls and T2DM participants,
      with T2DM demonstrating the greatest deficit in functional anisotropy (FA)
      volume, but these results were not significant after further controlling for BMI.
      Results from the current pilot study illuminate a host of brain morphology
      differences between youth with T2DM, obese youth, and normal-weight controls;
      future research with a larger sample size is critical. 

PMID- 26287286
TI  - Social participation in early and established rheumatoid arthritis patients.
AB  - PURPOSE: The aim of the study was to examine whether rheumatoid arthritis (RA)
      patients with different levels of restriction in social participation differ in
      disease related as well as psychosocial variables and whether a similar pattern
      can be found among early and established RA patients. METHOD: Two samples of RA
      patients with early (n = 97; age = 53 +/- 12.3 years; disease duration = 2.8 +/-
      1.2 years; 76% women) and established (n = 143; age = 58 +/- 10.3 years; disease
      duration = 16.1 +/- 3.6 years; 86% women) were collected. The pattern of
      differences for the patients with different level of participation restriction
      (no restriction, mild, moderate or high restriction) was explored by the
      Jonckheere-Terpstra test. RESULTS: Significant differences were found between
      patients with different levels of social participation restrictions in both
      samples in pain, fatigue, functional disability, anxiety, depression and mastery.
      Generally, it was found that patients with higher restrictions experienced more
      pain and fatigue, more anxiety and depression and reported lower mastery. Similar
      pattern of differences concerning disease activity and self-esteem was found
      mainly in the established group. CONCLUSIONS: The study shows that the level of
      perceived restrictions in social participation are highly relevant regarding the
      disease related variables such as pain, fatigue and functional disability as well
      as psychological status and personal resources in both early and established RA.
      IMPLICATIONS FOR REHABILITATION: Supporting involvement and participation of
      individuals with rheumatoid arthritis is important for decreasing the impact of
      RA symptoms on everyday life. Recognition and empowerment of individual resources
      such a mastery and self-esteem of RA patients could be beneficial for overcoming
      restrictions in participation.

PMID- 26287287
TI  - Continuous Postoperative Electronic Monitoring and the Will to Require It.

PMID- 26287288
TI  - The Power and Perils of Big Data: It All Depends on How You Slice, Dice, and
      Digest It.

PMID- 26287289
TI  - Great Expectations: A Case for Expanded Clinical Investigation.

PMID- 26287290
TI  - Test-Enhanced Learning in Flipped Classroom.

PMID- 26287291
TI  - Technology, Social Engineering, and Clinical Anesthesiology: Present and Future.

PMID- 26287292
TI  - HCN1 Channels as Targets for Volatile Anesthetics: Coming to the Fore.

PMID- 26287293
TI  - Pulmonary Impedance and Pulmonary Doppler Trace in the Perioperative Period.
AB  - Pulmonary hypertension and associated vascular changes may frequently accompany
      left-sided heart disease in the adult cardiac surgical population. Perioperative
      assessment of right ventricular function using echocardiography is well
      established. In general, understanding the constraints upon which the right
      ventricle must work is mostly limited to invasive monitoring consisting of
      pulmonary artery pressures, cardiac output, and pulmonary vascular resistance.
      The latter 2 measurements assume constant (mean) flows and pressures. The
      systolic and diastolic pressures offer a limited understanding of the pulsatile
      constraints, which may become significant in disease. In normal physiology,
      pressure and flow waves display near-similar contours. When left atrial pressure
      and pulmonary vascular resistance are increased, changes in pulmonary arterial
      compliance will result in elevated impedance to right ventricular ejection.
      Pressure reflections, the result of strong reflectors, return more quickly in a
      noncompliant system. They augment pulmonary artery pressure causing a premature
      reduction in flow. As a result, pressure and flow waves will now be dissimilar.
      The impact of vascular changes on right ventricular ejection can be assessed
      using pulmonary artery Doppler spectral imaging. The normal flow velocity profile
      is rounded at its peak. Earlier peaks and premature reductions in flow will make
      it appear more triangular. In some cases, the flow pattern may appear notched.
      The measurement of acceleration time, the time from onset to peak flow velocity
      is an indicator of constraint to ejection; shortened times have been associated
      with increased pulmonary vascular resistance and pressure. Understanding the
      changes in the pulmonary arterial system in disease and the physics of the
      hemodynamic alterations are essential in interpreting pulmonary artery Doppler
      data. Analyzing pulmonary artery Doppler flow signals may assist in the
      evaluation of right ventricular function in patients with pulmonary vascular
      disease. 

PMID- 26287294
TI  - Carbon Dioxide and the Heart: Physiology and Clinical Implications.
AB  - Carbon dioxide (CO2) is an end product of aerobic cellular respiration. In
      healthy persons, PaCO2 is maintained by physiologic mechanisms within a narrow
      range (35-45 mm Hg). Both hypercapnia and hypocapnia are encountered in myriad
      clinical situations. In recent years, the number of hypercapnic patients has
      increased by the use of smaller tidal volumes to limit lung stretch and injury
      during mechanical ventilation, so-called permissive hypercapnia. A knowledge and
      appreciation of the effects of CO2 in the heart are necessary for optimal
      clinical management in the perioperative and critical care settings. This article
      reviews, from a historical perspective: (1) the effects of CO2 on coronary blood
      flow and the mechanisms underlying these effects; (2) the role of endogenously
      produced CO2 in metabolic control of coronary blood flow and the matching of
      myocardial oxygen supply to demand; and (3) the direct and reflexogenic actions
      of CO2 on myocardial contractile function. Clinically relevant issues are
      addressed, including the role of increased myocardial tissue PCO2 (PmCO2) in the
      decline in myocardial contractility during coronary hypoperfusion and the
      increased vulnerability to CO2-induced cardiac depression in patients receiving a
      beta-adrenergic receptor antagonist or with otherwise compromised inotropic
      reserve. The potential use of real-time measurements of PmO2 to monitor the
      adequacy of myocardial perfusion in the perioperative period is discussed. 

PMID- 26287295
TI  - The Feasibility of Simultaneous Orthogonal Plane Imaging with Tilt for Short-Axis
      Evaluation of the Pulmonic Valve by Transesophageal Echocardiography.
AB  - Simultaneous orthogonal plane imaging with tilt enables the display of two 2D,
      real-time images and the evaluation of structures that cannot be seen by
      conventional single-plane transesophageal echocardiographic (TEE) imaging. After
      a step-wise examination protocol, we used simultaneous orthogonal plane imaging
      to obtain the short-axis view of the pulmonic valve (PV) and assessed flow in
      both images simultaneously using color Doppler imaging in 100 consecutive
      patients undergoing intraoperative TEE. Our goals were to assess the ability of
      this technique to visualize all 3 leaflets of the PV, assess feasibility of
      planimetry to measure valve area, and assess flow using color Doppler imaging.
      All study images were obtained by anesthesiologists who are diplomates in
      Advanced Perioperative Transesophageal Echocardiography. All 3 leaflets of the PV
      were successfully visualized in the short-axis view in 65% of cases, 2 leaflets
      were visualized in 32% of cases, and only 1 leaflet could be imaged in 3%. The
      flow across the valve could be evaluated using color Doppler imaging in all
      cases. Planimetry for valve area was possible when all 3 leaflets were seen. It
      is important to inspect the PV during a routine TEE examination; however, the
      orientation of the PV in respect to the esophagus makes this evaluation
      challenging. We present a simple protocol to evaluate the PV in long-axis and
      short-axis views simultaneously that can potentially help evaluate for
      pathologies involving the PV. 

PMID- 26287296
TI  - HCN1 Channels Contribute to the Effects of Amnesia and Hypnosis but not
      Immobility of Volatile Anesthetics.
AB  - BACKGROUND: Hyperpolarization-activated, cyclic nucleotide-gated (HCN) subtype 1
      (HCN1) channels have been identified as targets of ketamine to produce hypnosis.
      Volatile anesthetics also inhibit HCN1 channels. However, the effects of HCN1
      channels on volatile anesthetics in vivo are still elusive. This study uses
      global and conditional HCN1 knockout mice to evaluate how HCN1 channels affect
      the actions of volatile anesthetics. METHODS: Minimum alveolar concentrations
      (MACs) of isoflurane and sevoflurane that induced immobility (MAC of immobility)
      and/or hypnosis (MAC of hypnosis) were determined in wild-type mice, global HCN1
      knockout (HCN1) mice, HCN1 channel gene with 2 lox-P sites flanking a region of
      the fourth exon of HCN1 (HCN1) mice, and forebrain-selective HCN1 knockout (HCN1:
      cre) mice. Immobility of mice was defined as no purposeful reactions to tail
      clamping stimulus, and hypnosis was defined as loss of righting reflex. The
      amnestic effects of isoflurane and sevoflurane were evaluated by fear-potentiated
      startle in these 4 strains of mice. RESULTS: All MAC values were expressed as
      mean +/- SEM. For MAC of immobility of isoflurane, no significant difference was
      found among wild-type, HCN1, HCN1, and HCN1: cre mice (all ~1.24%-1.29%
      isoflurane). For both HCN1 and HCN1: cre mice, the MAC of hypnosis for isoflurane
      (each ~1.05% isoflurane) was significantly increased over their nonknockout
      controls: HCN1 versus wild-type (0.86% +/- 0.03%, P < 0.001) and HCN1: cre versus
      HCN1 mice (0.84% +/- 0.03%, P < 0.001); no significant difference was found
      between HCN1 and HCN1: cre mice. For MAC of immobility of sevoflurane, no
      significant difference was found among wild-type, HCN1, HCN1, and HCN1: cre mice
      (all ~2.6%-2.7% sevoflurane). For both HCN1 and HCN1: cre mice, the MAC of
      hypnosis for sevoflurane (each ~1.90% sevoflurane) was significantly increased
      over their nonknockout controls: HCN1 versus wild-type (1.58% +/- 0.05%, P <
      0.001) and HCN1: cre versus HCN1 mice (1.56% +/- 0.05%, P < 0.001). No
      significant difference was found between HCN1 and HCN1: cre mice. By fear
      potentiated startle experiments, amnestic effects of isoflurane and sevoflurane
      were significantly attenuated in HCN1 and HCN1: cre mice (both P < 0.002 versus
      wild-type or HCN1 mice). No significant difference was found between HCN1 and
      HCN1: cre mice. CONCLUSIONS: Forebrain HCN1 channels contribute to hypnotic and
      amnestic effects of volatile anesthetics, but HCN1 channels are not involved in
      the immobilizing actions of volatile anesthetics.

PMID- 26287297
TI  - E-mail as the Appropriate Method of Communication for the Decision-Maker When
      Soliciting Advice for an Intellective Decision Task.
AB  - For many problems in operating room and anesthesia group management, there are
      tasks with optimal decisions, and yet experienced personnel tend to make
      decisions that are worse or no better than random chance. Such decisions include
      staff scheduling, case scheduling, moving cases among operating rooms, and
      choosing patient arrival times. In such settings, operating room management
      leadership decision-making should typically be autocratic rather than
      participative. Autocratic-style decision-making calls for managers to solicit and
      consider feedback from stakeholders in the decision outcome but to make the
      decision themselves using their expert knowledge and the facts received. For this
      to be effective, often the manager will obtain expert advice from outside the
      organization (e.g., health system). In this narrative review, we evaluate the
      advantages and disadvantages of using prompt asynchronous written communication
      (i.e., e-mail) as a communication channel for such interaction between a decision
      maker (manager) and advisor. A detailed Appendix (Supplemental Digital Content,
      http://links.lww.com/AA/B72) lists each observational and experimental result. We
      find that the current ubiquitous role of e-mail for such communication is
      appropriate. Its benefits include improved time management via asynchronicity,
      low cognitive load (e.g., relative to Web conferencing), the ability to hide
      undesirable and irrelevant cues (e.g., physical appearance), the appropriateness
      of adding desirable cues (e.g., titles and degrees), the opportunity to provide
      written expression of confidence, and the ability for the advisor to demonstrate
      the answer for the decision-maker. Given that the manager is e-mailing an advisor
      whose competence the manager trusts, it is unnecessary to use a richer
      communication channel to develop trust. Finally, many of the limitations of e
      mail can be rectified through training. We expect that decades from now, e-mail
      (i.e., asynchronous writing) between an expert and decision-maker will remain the
      dominant means of communication for intellective tasks. 

PMID- 26287298
TI  - A Narrative Review of Meaningful Use and Anesthesia Information Management
      Systems.
AB  - The US federal government has enacted legislation for a federal incentive program
      for health care providers and hospitals to implement electronic health records.
      The primary goal of the Meaningful Use (MU) program is to drive adoption of
      electronic health records nationwide and set the stage to monitor and guide
      efforts to improve population health and outcomes. The MU program provides
      incentives for the adoption and use of electronic health record technology and,
      in some cases, penalties for hospitals or providers not using the technology. The
      MU program is administrated by the Department of Health and Human Services and is
      divided into 3 stages that include specific reporting and compliance metrics. The
      rationale is that increased use of electronic health records will improve the
      process of delivering care at the individual level by improving the communication
      and allow for tracking population health and quality improvement metrics at a
      national level in the long run. The goal of this narrative review is to describe
      the MU program as it applies to anesthesiologists in the United States. This
      narrative review will discuss how anesthesiologists can meet the eligible
      provider reporting criteria of MU by applying anesthesia information management
      systems (AIMS) in various contexts in the United States. Subsequently, AIMS will
      be described in the context of MU criteria. This narrative literature review also
      will evaluate the evidence supporting the electronic health record technology in
      the operating room, including AIMS, independent of certification requirements for
      the electronic health record technology under MU in the United States. 

PMID- 26287299
TI  - Postoperative Hypoxemia Is Common and Persistent: A Prospective Blinded
      Observational Study.
AB  - BACKGROUND: The incidence, severity, and duration of postoperative oxygen
      desaturation in the general surgical population are poorly characterized. We
      therefore used continuous pulse oximetry to quantify arterial oxygen saturation
      (SpO2) in a cross-section of patients having noncardiac surgery. METHODS: Oxygen
      saturation, blinded to clinicians, was recorded at 1-minute intervals in patients
      >45 years old for up to 48 hours after noncardiac surgery in 1250 patients from
      Cleveland Clinic Main Campus and 250 patients from the Juravinski Hospital. We
      determined (1) the cumulative minutes of raw minute-by-minute values below
      various hypoxemic thresholds; and (2) the contiguous duration of kernel-smoothed
      (sliding window) values below various hypoxemic thresholds. Finally, we compared
      our blinded continuous values with saturations recorded during routine nursing
      care. RESULTS: Eight hundred thirty-three patients had sufficient data for
      analyses. Twenty-one percent had >=10 min/h with raw SpO2 values <90% averaged
      over the entire recording duration; 8% averaged >=20 min/h <90%; and 8% averaged
      >=5 min/h <85%. Prolonged hypoxemic episodes were common, with 37% of patients
      having at least 1 (smoothed) SpO2 <90% for an hour or more; 11% experienced at
      least 1 episode lasting >=6 hours; and 3% had saturations <80% for at least 30
      minutes. Clinical hypoxemia, according to nursing records, measured only in
      Cleveland Clinic patients (n = 594), occurred in 5% of the monitored patients.
      The nurses missed 90% of smoothed hypoxemic episodes in which saturation was <90%
      for at least one hour. CONCLUSIONS: Hypoxemia was common and prolonged in
      hospitalized patients recovering from noncardiac surgery. The SpO2 values
      recorded in medical records seriously underestimated the severity of
      postoperative hypoxemia.

PMID- 26287300
TI  - The Effect of Hypothyroidism on a Composite of Mortality, Cardiovascular and
      Wound Complications After Noncardiac Surgery: A Retrospective Cohort Analysis.
AB  - BACKGROUND: We tested the hypothesis that hypothyroidism, as defined by thyroid
      stimulating hormone (TSH) concentration, is associated with a severity-weighted
      composite of mortality and major cardiovascular and infectious complications
      after noncardiac surgery. METHODS: In this retrospective cohort study, we
      evaluated adults at the Cleveland Clinic Main Campus between 2005 and 2012, who
      had had available TSH concentrations within the 6 months before noncardiac
      surgery. Patients were categorized as (1) hypothyroid (patients who had diagnosis
      of hypothyroidism any time prior to surgery and increased TSH value (> 5.5 mIU/L)
      within 6 months prior to surgery); (2) treated (hypothyroid diagnosis and normal
      TSH concentrations [0.4-5.5 mIU/L]); and (3) euthyroid (no hypothyroid diagnosis
      and normal TSH concentrations). We conducted pairwise comparisons among the 3
      groups using inverse propensity score weighting to control for observed
      confounding variables. Average relative effect generalized estimating equation
      model was used for the primary outcome composite of in-hospital cardiovascular
      morbidity, surgical wound complication or infection, and mortality. Logistic
      regression and Cox proportional hazards regression were used for secondary
      outcomes of intraoperative vasopressor use and duration of hospitalization,
      respectively. RESULTS: We identified 800 hypothyroid patients (median TSH: 8.6
      mIU/L [Q1, Q3: 6.5, 13.0]), 1805 treated patients (2.0 mIU/L [1.1, 3.2]), and
      5612 euthyroid patients (1.7 mIU/L [1.1, 2.6]). There were no significant
      differences among the hypothyroid, treated, and euthyroid patients on the primary
      composite outcome (all P values >=0.30). Hypothyroid patients were slightly more
      likely to receive vasopressor during surgery than either treated (odds ratio,
      1.17; 99.2% confidence interval [CI], 1.01-1.36) or euthyroid (odds ratio, 1.12;
      99.2% CI, 1.02-1.24) patients. Furthermore, hypothyroid patients were slightly
      but significantly less likely to be discharged at any given postoperative time
      than treated patients (hazard ratio, 0.92; 99.2% CI, 0.86-0.99). CONCLUSIONS:
      Hypothyroidism was not associated with worse postoperative mortality, wound, or
      cardiovascular outcomes in noncardiac patients. Thus, postponing surgery to
      initiate thyroid replacement therapy in patients with hypothyroidism seems
      unnecessary.

PMID- 26287301
TI  - All That Glitters Is Not a Golden Recommendation.

PMID- 26287302
TI  - Dexmedetomidine Improves Intubating Conditions Without Muscle Relaxants in
      Children After Induction With Propofol and Remifentanil.
AB  - BACKGROUND: Anesthesia induction using propofol (3 mg/kg) and remifentanil (2
      MUg/kg) without the use of muscle relaxants has been associated with a lower
      incidence of successful intubation. Dexmedetomidine has been found to effectively
      decrease the requirements for propofol and remifentanil and to attenuate the
      hemodynamic response to intubation. Therefore, in this study, we examined
      intubating conditions and hemodynamic changes in children after induction with
      dexmedetomidine (1 MUg/kg) combined with propofol (3 mg/kg) and remifentanil (2
      MUg/kg). METHODS: This randomized, double-blinded, and placebo-controlled study
      included 60 ASA physical status I children aged 5 to 10 years. The children were
      randomly allocated to a dexmedetomidine group (group D) or a placebo group (group
      P). After IV administration of atropine (0.01 mg/kg), anesthesia was induced with
      an infusion of dexmedetomidine (1 MUg/kg) over 2 minutes for group D, whereas
      normal saline was infused for group P. Propofol (3 mg/kg) was then injected IV
      over 20 to 30 seconds, followed by an infusion of remifentanil (2 MUg/kg) over 1
      minute for both groups. One minute later, laryngoscopy and tracheal intubation
      were performed. RESULTS: For group D and group P, tracheal intubation was
      successful in 90% (27/30) and 53% (16/30) of patients (P = 0.0034), respectively.
      Excellent conditions were present in 22 of 27 and 8 of 16 of intubations,
      respectively, resulting in an overall incidence of excellent conditions of 73%
      (22/30) and 27% (8/30), respectively (P = 0.0007). Systolic blood pressure
      significantly increased after the IV injection of dexmedetomidine compared with
      baseline readings (P = 0.012, with a confidence interval of 2-22 mm Hg).
      CONCLUSIONS: A single dose of dexmedetomidine (1 MUg/kg) improved intubation
      conditions in children after induction with propofol (3 mg/kg) and remifentanil
      (2 MUg/kg) without muscle relaxants. Dexmedetomidine did not affect the
      hemodynamic response to intubation.

PMID- 26287303
TI  - Ebola Virus Disease: A Review of Its Past and Present.
AB  - Ebola virus, the virus responsible for Ebola virus disease, has spawned several
      epidemics during the past 38 years. In 2014, an Ebola epidemic spread from Africa
      to other continents, becoming a pandemic. The virus's relatively unique
      structure, its infectivity and lethality, the difficulty in stopping its spread,
      and the lack of an effective treatment captured the world's attention. This
      article provides a brief review of the known history of Ebola virus disease, its
      etiology, epidemiology, and pathophysiology and a review of the limited
      information on managing patients with Ebola virus disease. 

PMID- 26287304
TI  - A Tale of Silent Aspiration: Are Guidelines Good for Every Patient?

PMID- 26287305
TI  - Managing Ebola: Lessons Learned from the SARS Epidemic.

PMID- 26287306
TI  - Smart Operating Room Music.

PMID- 26287307
TI  - In Response.

PMID- 26287308
TI  - The Implementation of Quantitative Electromyographic Neuromuscular Monitoring in
      an Academic Anesthesia Department: Follow-Up Observations.

PMID- 26287309
TI  - Correlating the Morphological Properties and Structural Organization of
      Monodisperse Spherical Silica Nanoparticles Grown on a Commercial Silica Surface.
AB  - A variety of nanosilicas have been widely used to fabricate rough surfaces with
      superhydrophobic and superhydrophilic properties. In this context, we prepared
      mixed silica and mixed nanosilica that were generated by the growth and self
      assembly of synthesized monodisperse silica nanospheres (11-30 nm, 363 m(2)  g(
      1) ) on the surface of Sylopol-948 and Dispercoll S3030 by using a base-catalyzed
      sol-gel route. Using this process, the interactions and hierarchical structure
      between the nano- and microsized synthesized silica particles were studied by
      changing the amount of tetraethoxysilane. The resulting materials were
      characterized by BET analysis, small-angle X-ray scattering (SAXS), dynamic light
      scattering, FTIR spectroscopy, and SEM. The mixed silica presented a higher
      specific surface area (326 m(2)  g(-1) ), a six-fold higher percentage of (SiO)6
      (44-68 %), and a higher amount of silanol groups (14.0-30.7 %) than Sylopol-948
      (271 m(2)  g(-1), 42.6 %, and 12.5 %, respectively). The morphological and
      hierarchical structural differences in the silica nanoparticles synthesized on
      the surface of commercial silica (micrometric or nanometric) were identified by
      SAXS. Mixed micrometric silica exhibited a higher degree of structural
      organization between particles than mixed nanosilica.

PMID- 26287310
TI  - Potent and Selective Inhibitors of Histone Deacetylase-3 Containing Chiral
      Oxazoline Capping Groups and a N-(2-Aminophenyl)-benzamide Binding Unit.
AB  - A novel series of potent chiral inhibitors of histone deacetylase (HDAC) is
      described that contains an oxazoline capping group and a N-(2-aminophenyl)
      benzamide unit. Among several new inhibitors of this type exhibiting Class I
      selectivity and potent inhibition of HDAC3-NCoR2, in vitro assays for the
      inhibition of HDAC1, HDAC2, and HDAC3-NCoR2 by N-(2-aminophenyl)-benzamide 15k
      gave respective IC50 values of 80, 110, and 6 nM. Weak inhibition of all other
      HDAC isoforms (HDAC4, 5, 6, 7, and 9: IC50 > 100 000 nM; HDAC8: IC50 = 25 000 nM;
      HDAC10: IC50 > 4000 nM; HDAC11: IC50 > 2000 nM) confirmed the Class I selectivity
      of 15k. 2-Aminoimidazolinyl, 2-thioimidazolinyl, and 2-aminooxazolinyl units were
      shown to be effective replacements for the pyrimidine ring present in many other
      2-(aminophenyl)-benzamides previously reported, but the 2-aminooxazolinyl unit
      was the most potent in inhibiting HDAC3-NCoR2. Many of the new HDAC inhibitors
      showed higher solubilities and lower binding to human serum albumin than that of
      Mocetinostat. Increases in histone H3K9 acetylation in the human cell lines U937
      and PC-3 was observed for all three oxazolinyl inhibitors evaluated; those HDAC
      inhibitors also lowered cyclin E expression in U937 cells but not in PC-3 cells,
      indicating underlying differences in the mechanisms of action of the inhibitors
      on those two cell lines.

PMID- 26287311
TI  - Transient Absorption: A New Modality for Microscopic Imaging of Nanomaterials in
      Living Cells.
AB  - Transient absorption is a secondary absorption that happens after a material has
      been excited through primary absorption. Different mechanisms can contribute to
      transient absorption. This universal photophysical process exists in almost all
      types of nanomaterials, making it an ideal modality to monitor the location,
      dynamics, and interactions of nanomaterials in living cells, tissues, or animals.
      With two beams of lasers and a scanning microscope, transient absorption
      microscopy is able to acquire high-resolution, 3D images at high speed, without
      the need for labeling. Through time-delay adjustments of pulse trains, this novel
      method can also reveal background-free images of specific nanomaterials, even
      with the interference of high concentrations of fluorophores. 

PMID- 26287312
TI  - Reactivity of Phosphanylphosphinidene Complex of Tungsten(VI) toward Phosphines:
      A New Method of Synthesis of catena-Polyphosphorus Ligands.
AB  - The reactivity of an anionic phosphanylphosphinidene complex of tungsten(VI),
      [(2,6-i-Pr2C6H3N)2(Cl)W(eta(2)-t-Bu2P?P)]Li.3DME toward PMe3, halogenophosphines,
      and iodine was investigated. Reaction of the starting complex with Me3P led to
      formation of a new neutral phosphanylphosphinidene complex, [(2,6-i
      Pr2C6H3N)2(Me3P)W(eta(2)-t-Bu2P?P)]. Reactions with halogenophosphines yielded
      new catena-phosphorus complexes. From reaction with Ph2PCl and Ph2PBr, a complex
      with an anionic triphosphorus ligand t-Bu2P-P((-))-PPh2 was isolated. The main
      product of reaction with PhPCl2 was a tungsten(VI) complex with a pentaphosphorus
      ligand, t-Bu2P-P((-))-P(Ph)-P((-))-P-t-Bu2. Iodine reacted with the starting
      complex as an electrophile under splitting of the P-P bond in the t-Bu2P?P unit
      to yield [(1,2-eta-t-Bu2P-P-P-t-Bu2)W(2,6-i-Pr2C6H3N)2Cl], t-Bu2PI, and
      phosphorus polymers. The molecular structures of the isolated products in the
      solid state and in solution were established by single crystal X-ray diffraction
      and NMR spectroscopy. 

PMID- 26287313
TI  - Xylem parenchyma cell walls lack a gravitropic response in conifer compression
      wood.
AB  - MAIN CONCLUSION: Cell wall fluorescence and immunocytochemistry demonstrate that
      xylem parenchyma cell walls do not show changes in structure and composition
      related to gravitropic response comparable to those of tracheids, even when they
      have lignified secondary cell walls. Tracheid cell walls in compression wood have
      altered composition and structure which generates the strain responsible for
      correction of stem lean as part of the gravitropic response of woody plants.
      Xylem parenchyma cell walls vary among conifer species and can be lignified
      secondary walls (spruce) or unlignified primary walls (pine). It can be expected
      that xylem parenchyma with lignified secondary cell walls might show features of
      compression wood comparable to those of tracheids that have a similar type of
      cell wall. A comparison of xylem parenchyma cell walls in normal and compression
      wood in species with lignified and non-lignified parenchyma cell walls provides a
      unique opportunity to understand the process of reaction wood formation in
      conifers. Using both UV/visible fluorescence microscopy of cell wall fluorophores
      and immunocytochemistry of galactan and mannan epitopes, we demonstrate that
      xylem parenchyma cell walls do not show the changes in composition and structure
      typical of compression wood tracheids. Adjacent cells of different types but with
      similar cell wall structure can undergo cell wall developmental changes related
      to support or defence functions independent of their neighbours. Tracheids are
      sensitive to gravitropic signals while xylem parenchyma cells are not.

PMID- 26287314
TI  - Identifying the ideal metric of proteinuria as a predictor of renal outcome in
      idiopathic glomerulonephritis.
AB  - The majority of our insight about glomerulonephritis (GN) is from observational
      research. Because proteinuria is an important element of outcome in GN, the
      validity of observational analyses is dependent on the metric used to model
      proteinuria. Previous metrics of proteinuria included the value at baseline, the
      average of all values over the entire follow-up (time-averaged), the
      instantaneous value at each time point (time-varying), or the average of all
      values prior to each time point, and each of these standardized to body surface
      area. It was not known which of these metrics best accounts for the risk of renal
      outcome and should be used in GN research. To address this, we studied 1351 adult
      patients with IgA nephropathy, focal segmental glomerulosclerosis, and membranous
      nephropathy from the Toronto GN Registry. Cox regression models for the risk of
      end-stage renal disease or a halving of estimated glomerular filtration rate
      included each proteinuria metric and were compared using model fit and
      discrimination. Proteinuria did not need to be standardized to body surface area.
      Time-varying proteinuria was the best metric to account for the prognostic
      effects of proteinuria over time, especially in focal segmental
      glomerulosclerosis and IgA nephropathy over the majority of follow-up, and in
      membranous nephropathy earlier in the disease course. Using alternate proteinuria
      metrics biased analyses up to 30.3%. These findings can improve the validity and
      design of future observational and prediction modeling studies in GN.

PMID- 26287315
TI  - Urinary mitochondrial DNA is a biomarker of mitochondrial disruption and renal
      dysfunction in acute kidney injury.
AB  - Recent studies show the importance of mitochondrial dysfunction in the initiation
      and progression of acute kidney injury (AKI). However, no biomarkers exist
      linking renal injury to mitochondrial function and integrity. To this end, we
      evaluated urinary mitochondrial DNA (UmtDNA) as a biomarker of renal injury and
      function in humans with AKI following cardiac surgery. mtDNA was isolated from
      the urine of patients following cardiac surgery and quantified by quantitative
      PCR. Patients were stratified into no AKI, stable AKI, and progressive AKI groups
      based on Acute Kidney Injury Network (AKIN) staging. UmtDNA was elevated in
      progressive AKI patients and was associated with progression of patients with AKI
      at collection to higher AKIN stages. To evaluate the relationship of UmtDNA to
      measures of renal mitochondrial integrity in AKI, mice were subjected to sham
      surgery or varying degrees of ischemia followed by 24 h of reperfusion. UmtDNA
      increased in mice after 10-15 min of ischemia and positively correlated with
      ischemia time. Furthermore, UmtDNA was predictive of AKI in the mouse model.
      Finally, UmtDNA levels were negatively correlated with renal cortical mtDNA and
      mitochondrial gene expression. These translational studies demonstrate that
      UmtDNA is associated with recovery from AKI following cardiac surgery by serving
      as an indicator of mitochondrial integrity. Thus UmtDNA may serve as valuable
      biomarker for the development of mitochondrial-targeted therapies in AKI.

PMID- 26287316
TI  - Aneurysm Needle as an Effective Tool in Laparoscopic Port Closure.
AB  - The importance of port closure after laparoscopic surgeries is emphasized by the
      extensive number of techniques being described for the same. Even so, the search
      for a simple, time-saving, and effective technique still continues. One commonly
      overlooked factor is the obliquity of laparoscopic ports, which makes direct
      visualization of the rectus fascia through the skin incision difficult. Also, our
      patients, mostly of Indian ethnicity, tend to have relatively thick subcutaneous
      fat that again acts as a constraint during port closure. We have described a
      simple and effective method of laparoscopic port closure using Moynihan's
      aneurysm needle and a skin hook. This technique is particularly advantageous in
      the above-mentioned scenarios. We have been successfully using this technique in
      our institution for the past 6 years, and we have not encountered any case of
      port-site hernia. Our technique does not require expensive instruments or the
      need for visualization via a camera. 

PMID- 26287317
TI  - Genes and environment as predisposing factors in autoimmunity: acceleration of
      spontaneous thyroiditis by dietary iodide in NOD.H2(h4) mice.
AB  - In the field of autoimmune thyroiditis, NOD.H2(h4) mice have attracted
      significant and increasing attention since they not only develop spontaneous
      disease but they present thyroiditis with accelerated incidence and severity if
      they ingest iodide through their drinking water. This animal model highlights the
      interplay between genetic and dietary factors in the triggering of autoimmune
      disease and offers new opportunities to study immunoregulatory parameters
      influenced by both genes and environment. Here, we review experimental findings
      with this mouse model of thyroiditis. 

PMID- 26287318
TI  - Alpha-1 Antitrypsin Deficiency and Lung Cancer Risk: A Case-Control Study in
      Never-Smokers.
AB  - BACKGROUND: Never-smokers comprise up to 25% of all lung cancer cases. They could
      have different molecular pathways for lung cancer induction compared with
      smokers. Alpha-1 antitrypsin (AAT) deficiency is a hereditary trait whose main
      characteristic is early onset of lung emphysema. Our aim is to know if AAT
      deficient carriers have a higher risk of lung cancer in a study performed
      exclusively in never-smokers. METHODS: We designed a multicentre hospital-based
      case-control study, which included incident never-smoking lung cancer cases.
      Controls were never-smokers attending nonmajor surgery at the participating
      hospitals. Controls were frequency matched on age and gender with cases. We
      determined AAT variants (alleles S and Z) through polymerase chain reaction.
      RESULTS: Two hundred and twelve cases and 318 controls were included. PiSS
      individuals showed a lung cancer risk of 4.64 (95% confidence interval: 1.08
      19.92) compared with those with normal genotype (PiMM). When the analysis was
      restricted to women, the risk for PiSS increased to 7.58 (95% confidence
      interval: 1.40-40.87). This risk for homozygous SS was even higher for
      individuals exposed to environmental tobacco smoke (greater than 20 years). The
      presence of other alleles did not show any effect on lung cancer risk.
      CONCLUSIONS: Never smoking SS homozygous individuals pose an increased risk of
      lung cancer. The risk is higher for individuals exposed to environmental tobacco
      smoke.

PMID- 26287319
TI  - Perioperative versus Preoperative Chemotherapy with Surgery in Patients with
      Resectable Squamous Cell Carcinoma of Esophagus: A Phase III Randomized Trial.
AB  - BACKGROUND: Perioperative chemotherapy for resectable squamous cell carcinoma of
      esophagus remains elusive. Thus, we assessed whether a perioperative regimen of
      paclitaxel, cisplatin, and 5- fluorouracil (PCF) improved outcomes among patients
      with curable squamous cell carcinoma of esophagus comparing with preoperative
      chemotherapy alone. METHODS: Overall, 346 patients with resectable squamous cell
      carcinoma of esophagus were randomly assigned to receive surgery plus
      perioperative chemotherapy (175, arm A) or preoperative chemotherapy (171, arm
      B). Both arms received two preoperative cycles of PCF: intravenous paclitaxel
      (100 mg per square meter of body surface area) and cisplatin (60 mg per square
      meter of body surface area) on day 1, and a continuous intravenous infusion of 5-
      fluorouracil (700 mg per square meter of body surface area per day) for 5 days.
      Arm A received two added postoperative cycles of PCF. The primary end point was
      relapse-free survival, and the secondary end point was overall survival. RESULTS:
      Compared with preoperative chemotherapy group, perioperative chemotherapy group
      had a greater likelihood of 5-year relapse-free survival (hazard ratio for
      relapse, 0.62; 95% confidence interval, 0.49-0.73; 31% versus 17%, p < 0.001) and
      of 5-year overall survival (hazard ratio for death, 0.79; 95% confidence
      interval, 0.59-0.95; 38% versus 22%, p < 0.001). A pathologic complete response
      rate was achieved in 77 of 320 patients (24.1%) who underwent resection after
      chemotherapy. The increased PCF-related toxic events were not detected with the
      addition of two postoperative cycles of PCF. CONCLUSION: In patients with
      operable esophageal squamous cell carcinoma, perioperative regimen of PCF can
      significantly improve 5-year relapse-free and overall survival comparing with
      preoperative chemotherapy alone. (The trial has been registered at
      ClinicalTrials.gov, number NCT01225523.).

PMID- 26287322
TI  - [Social Media in Surgery?].

PMID- 26287320
TI  - Should Never-Smokers at Increased Risk for Lung Cancer Be Screened?
AB  - INTRODUCTION: Lung cancer in never-smokers ranks among the 10 most common causes
      of death due to cancer worldwide and in the United States. However, it is unknown
      whether never-smokers at elevated risk for developing lung cancer may benefit
      from lung cancer screening. METHODS: The MIcrosimulation SCreening ANalysis
      (MISCAN)-Lung microsimulation model was used to assess the effects of lung cancer
      screening for simulated cohorts of never-smokers at different levels of relative
      risk (RR) for lung cancer compared with never-smokers at average risk. The
      benefits and harms of screening were estimated for each cohort and compared with
      those of a cohort of ever-smokers eligible for lung cancer screening according to
      the United States Preventive Services Task Force (USPSTF) criteria. RESULTS: The
      relative lung cancer mortality reduction in never-smokers was higher than the
      USPSTF eligible cohort (37% compared with 32%). However, the number of life-years
      gained per lung cancer death averted was lower (10.4 compared with 11.9) and the
      proportion of overdiagnosed cancers was higher (9.6% compared with 8.4%) for
      never-smokers compared with the USPSTF eligible cohort, as never-smokers are
      diagnosed at a later age. The estimated number of screens per lung cancer death
      averted ranged from 6162 for never-smokers at average risk to 151 for never
      smokers with an RR of 35 compared with 353 for the USPSTF eligible cohort.
      CONCLUSIONS: Never-smokers with RRs of 15 to 35 have similar to better trade-offs
      between benefits and harms compared with ever-smokers recommended for lung cancer
      screening by the USPSTF guidelines. For most never-smokers, lung cancer screening
      is not beneficial.

PMID- 26287323
TI  - [Independence in Plastic Surgery - Benefit or Barrier? Analysis of the
      Publication Performance in Academic Plastic Surgery Depending on Varying
      Organisational Structures].
AB  - INTRODUCTION: Despite its recognition as an independent specialty, at German
      university hospitals the field of plastic surgery is still underrepresented in
      terms of independent departments with a dedicated research focus. The aim of this
      study was to analyse the publication performance within the German academic
      plastic surgery environment and to compare independent departments and dependent,
      subordinate organisational structures regarding their publication performance.
      MATERIAL AND METHODS: Organisational structures and number of attending doctors
      in German university hospitals were examined via a website analysis. A pubmed
      analysis was applied to assess the publication performance (number of
      publications, cumulative impact factor, impact factor/publication, number of
      publications/MD, number of publications/unit) between 2009 and 2013. In a journal
      analysis the distribution of the cumulative impact factor and number of
      publications in different journals as well as the development of the impact
      factor in the top journals were analysed. RESULTS: Out of all 35 university
      hospitals there exist 12 independent departments for plastic surgery and 8
      subordinate organisational structures. In 15 university hospitals there were no
      designated plastic surgery units. The number of attending doctors differed
      considerably between independent departments (3.6 attending doctors/unit) and
      subordinate organisational structures (1.1 attending doctors/unit). The majority
      of publications (89.0%) and of the cumulative impact factor (91.2%) as well as
      most of the publications/MD (54 publications/year) and publications/unit (61
      publications/year) were created within the independent departments. Only in
      departments top publications with an impact factor > 5 were published. In general
      a negative trend regarding the number of publications (- 13.4%) and cumulative
      impact factor (- 28.9%) was observed. 58.4% of all publications were distributed
      over the top 10 journals. Within the latter the majority of articles were
      published in English journals (60% of publications, 79.9% of the cumulative
      impact factor). The average impact factor of the top 10 journals increased by
      13.5% from 2009 to 2013. CONCLUSION: In contrast to subordinate and dependent
      organisational structures, independent departments of plastic surgery are the key
      performers within German academic plastic surgery which, however, suffers from a
      general declining publication performance. Hence, the type of organisational
      structure has a crucial influence on the research performance.

PMID- 26287324
TI  - [The DIEP Flap as Method of Choice in Breast Reconstruction - Results and
      Protocol for Succesful Reconstruction].
AB  - BACKGROUND: Autologous breast reconstruction is becoming increasingly important,
      especially in light of the increased rates of prophylactic mastectomies with BRCA
      mutations. Regarding the indications and complications between free TRAM and free
      DIEP flaps for autologous breast reconstruction the current data is not clear.
      MATERIALS AND METHODS: All patients who received an autologous breast
      reconstruction between January 2010 and January 2014 using free DIEP or free MS-2
      TRAM flaps were included in the study. The choice of flap between DIEP and MS-2
      TRAM was performed by a standardised algorithm with preoperative CT angiography,
      intraoperative evaluation of the flap perfusion and Doppler detection. The
      analysis took into account partial flap necrosis <20% and >20%), complete flap
      loss, flap necrosis and surgical revision of the anastomosis. RESULTS: The study
      considered 362 women who received a total of 419 free flaps for breast
      reconstruction. 66 patients received a bilateral reconstruction (52 double DIEPS,
      9 DIEP and MS2 TRAM and 5 double MS2 TRAMs). The total flap loss was 0.24%.
      Partial necrosis <20% occurred in 0.72% (DIEP 0.82%, MS2 TRAM 0%), partial
      necrosis >20% in 0.72% (DIEP 0.69% MS2 TRAM 0.98%). One DIEP flap was lost
      (0.24%). After implementing our protocol the rate of MS-2-Tram flaps could be
      reduced to 10-15% of all autologous breast reconstruction procedures as compared
      to the years before. CONCLUSION: Through the application of the presented
      algorithm for breast reconstruction with free DIEP flap, such surgery is a safe
      treatment option if it is done at high frequency in a microsurgical centre. Flap
      loss and complications are not increased compared to MS2 TRAM flaps. The decision
      for the selection of the appropriate flap for breast reconstruction should be
      based on the presented algorithm in order to achieve secure and reproducible
      results.

PMID- 26287325
TI  - [Prevention of Occupational Injuries Related to Hands: Calculation of Subsequent
      Injury Costs for the Austrian Social Occupational Insurance Institution (AUVA)].
AB  - MOTIVATION: Occupational injuries cause short-term, direct costs as well as long
      term follow-up costs over the lifetime of the casualties. Due to shrinking
      budgets accident insurance companies focus on cost reduction programmes and
      prevention measures. For this reason, a decision support system for consequential
      cost calculation of occupational injuries was developed for the main Austrian
      social occupational insurance institution (AUVA) during three projects. METHODS:
      This so-called cost calculation tool combines the traditional instruments of
      accounting with quantitative methods such as micro-simulation. The cost data are
      derived from AUVA-internal as well as external economic data sources. Based on
      direct and indirect costs, the subsequent occupational accident costs from the
      time of an accident and, if applicable, beyond the death of the individual
      casualty are predicted for the AUVA, the companies in which the casualties are
      working, and the other economic sectors. RESULTS: By using this cost calculation
      tool, the AUVA classifies risk groups and derives related prevention campaigns.
      In the past, the AUVA concentrated on falling, accidents at construction sites
      and in agriculture/forestry, as well as commuting accidents. Currently, among
      others, a focus on hand injuries is given and first prevention programmes have
      been initiated. Hand injuries represent about 38% of all casualties with average
      costs of about 7,851 Euro/case. Main causes of these accidents are cutting
      injuries in production, agriculture, and forestry. Beside a low, but costly,
      number of amputations with average costs of more than 100,000 Euro/case, bone
      fractures and strains burden the AUVA-budget with about 17,500 and 10,500 ? per
      case, respectively. CONCLUSION: Decision support systems such as this cost
      calculation tool represent necessary instruments to identify risk groups and
      their injured body parts, causes of accidents, and economic activities, which
      highly burden the budget of an injury company, and help derive countermeasures to
      avoid injuries. Target-group specific, suitable prevention measures for hand
      injuries can reduce accidents in a cost-effective way and lower their
      consequences.

PMID- 26287326
TI  - [The Assessment of REC after Thermal Trauma as Part of the Appraisal Process for
      Statutory Accident Insurance in Germany (Part 1): Low Validity of the REC Form
      Developed by Donnersmarck and Horbrand].
AB  - The total REC (reduction in earning capacity) after a thermal trauma is usually
      assessed using an appraisal form for burns victims, initially developed by
      Hoerbrandt and von Donnersmarck (1995). The criteria for functional impairment,
      local findings and vegetative-somatic complaints are somewhat imprecise given the
      broad scope of interpretation which the evaluator can employ in making an
      appraisal. This means that the overall appraisal of REC is subjective on the part
      of the evaluator. In addition, one can only calculate an overall REC of at most
      40% from local findings and vegetative-somatic symptoms, even in patients with
      extensive large area burns. Considering these points we investigated the
      dependency of the results on the evaluator as well as the limited validity of the
      appraisal form originally developed by Horbrand and Donnersmark. 

PMID- 26287327
TI  - [Ten Cases of Cryptotia Corrected using Ono's Technique].
AB  - Cryptotia is a very rare condition of ear deformity found in Europe which is more
      common in Asian populations. The upper ear portion is hidden and fixed in a
      pocket of skin of the mastoid. Conservatively, this deformity can be treated by
      molding of the posterior sulcus starting early after birth. Various surgical
      procedures are described in the literature. We successfully operated on a total
      of 10 ears of 9 patients with the technique described by Ichiro Ono in 1995.
      Here, a triangular flap is raised above the ear to reconstruct the posterior
      sulcus together with a rhomboid-shaped flap in the anterior part of the ear in
      order to elongate the helix. Among all patients, regular contours and a stable
      and successful outcome was observed. 

PMID- 26287328
TI  - [Viability and Particle Size of Fat Grafts Obtained with WAL and PAL Techniques].
AB  - BACKGROUND: Water jet-assisted liposuction (WAL) and power-assisted liposuction
      (PAL) are used for autologous fat grafting. This study analyses the viability and
      particle sizes of fat grafts obtained by these techniques. PATIENTS, MATERIAL AND
      METHODS: The WAL and PAL techniques were applied in 9 female patients in
      identical body regions. In order to analyse cell viability, fat grafts were
      tested via the WST-8 assay and DNA quantification immediately after liposuction.
      Furthermore, in order to determine particle size, an optically evaluable water
      fat emulsion was analysed by macroscopic inspection and light microscopy.
      RESULTS: The WST-8 assay showed significantly lower extinction values (OD) for
      use of the WAL technique - corresponding to a lower metabolical activity -
      compared to PAL liposuction: WAL 1.85+/-0.56 OD, PAL 2.25+/-0.57 OD. The quotient
      of extinction values and cell DNA concentration determined by DNA quantification
      also indicated statistically significant differences between both systems of
      liposuction in favour of using power-assisted systems: WAL 0.061+/-0.023 OD/MUg,
      PAL 0.083+/-0.029 OD/MUg. On the other hand, microscopic and macroscopic analyses
      showed significantly greater diameters (d) for fat grafts obtained with the PAL
      technique than by WAL liposuction: dmakroWAL=0.8 mm and dmakroPAL=1.1 mm or,
      respectively, dmikroWAL 0.89 mm and dmikroPAL=0.93 mm. CONCLUSION: Power-assisted
      liposuction obtains fat grafts with a higher metabolical activity than water jet
      assisted liposuction. A falsification of extinction values within the WST-8 assay
      due to diversity of the number of cells was eliminated by additionally
      implemented DNA quantification. According to the current scientific debate, the
      particle size of obtained fat grafts is also considered as an important criterion
      for the success of autologous fat grafting. For clinical use, one should favour
      techniques which provide the smallest and most viable fat grafts as possible. In
      our opinion, the significantly lower size of WAL particles compared to the higher
      viability of PAL grafts indicates a necessity of analysing viability as well as
      particle size in order to evaluate liposuction systems. Data solely about in
      vitro viability of fat grafts fail to offer a recommendation for the use of a
      specific technique.

PMID- 26287329
TI  - [Delayed Infection after Upper Lip Augmentation with Absorbable Hyaluronic Acid
      Filler].
AB  - Since introduction of the first fillers in the 1980s a multitude of substances
      has been developed and approved for facial contour augmentation and correction of
      skin defects. Here we present the interesting case of a patient who presented to
      us with a delayed infection 6 weeks after augmentation of the upper lip with a
      hyaluronic acid. We observed full convalescence after operative and high-dose
      antibiotic treatment of the abscesses. Generally speaking, complications after
      augmentation with resorbable fillers are rare. However, complications might occur
      even within unexpected time periods and therefore need our special attention. 

PMID- 26287330
TI  - [Current Concepts of Microsurgical Procedures in the Treatment of Lymphedemas of
      the Upper Extremity].

PMID- 26287331
TI  - [Aesthetic Surgery and Value-Added Tax].

PMID- 26287332
TI  - A Rationally Designed Upconversion Nanoprobe for in Vivo Detection of Hydroxyl
      Radical.
AB  - The detection of *OH in live organisms is crucial to the understanding of its
      physiological and pathological roles; while this is too challenging because of
      the extremely low concentration and high reactivity of the species in the body.
      Herein, we report the rational design and fabrication of an NIR-light excited
      luminescence resonance energy transfer-based nanoprobe, which for the first time
      realizes the in vivo detection of *OH. The nanoprobe is composed of two moieties:
      upconversion nanoparticles with sandwich structure and bared surface as the
      energy donor; and mOG, a modified azo dye with tunable light absorption, as both
      the energy acceptor and the *OH recognizing ligand. The as-constructed nanoprobe
      exhibited ultrahigh sensitivity (with the quantification limit down to 1.2
      femtomolar, several orders of magnitude lower than that of most previous *OH
      probes), good biocompatibility, and specificity. It was successfully used for
      monitoring [*OH] levels in live cells and tissues. 

PMID- 26287333
TI  - A vertical-oriented WS2 nanosheet sensitized by graphene: an advanced
      electrocatalyst for hydrogen evolution reaction.
AB  - Electrocatalytic hydrogen production at low overpotential is a promising route
      towards a clean and sustainable energy. Layered transition metal dichalcogenides
      (LTMDs) have attracted copious attention for their outstanding activities in
      hydrogen evolution reaction (HER). However, the horizontally laid nanosheets
      suffer from a paucity of active edge sites. Herein, we report the successful
      synthesis of vertical-oriented WS2 nanosheets through a hydrothermal method
      followed by a facile sulfurization process. Furthermore, the surface of
      synthesized WS2 nanosheets was decorated by ultrathin reduced graphene oxide
      (rGO) nanoplates. This is achieved for the first time by bringing the rGO on the
      surface of vertical-oriented WS2 nanosheets, which is conducive to rapid electron
      transport during the HER process. Significantly, the as-synthesized rGO/WS2
      nanosheets exhibit improved HER activity as compared to the undecorated ones. It
      needs a low overpotential of only 229 mV vs. RHE to afford a current density of
      10 mA cm(-2). We believe that this hybrid structure demonstrated remarkable HER
      activity brought about by a compatible synergism between rGO and WS2. 

PMID- 26287335
TI  - [Effects of obesity on peak level of luteinizing hormone in gonadotropin
      releasing hormone agonist test and obesity-related hormones in girls with central
      precocious puberty].
AB  - OBJECTIVE: To explore the effects of obesity on the peak level of luteinizing
      hormone (LH) in the gonadotropin-releasing hormone (GnRH) agonist test and
      obesity-related hormones in girls with central precocious puberty (CPP). METHODS:
      Three hundred and thirty-three girls with CPP who underwent the GnRH agonist test
      between 2012 and 2014 were classified into three groups: normal weight (n=123),
      overweight (n=108), and obesity (n=102), according to body mass index (BMI). The
      sexual development indices were compared between the three groups. Twenty girls
      were randomly selected from each group for evaluation of the serum levels of
      leptin, sex hormone binding globulin (SHBG), neurokinin B, and kisspeptin. The
      correlation of BMI with the levels of various hormones was assessed using Pearson
      correlation analysis. RESULTS: There was no significant difference in mean age at
      diagnosis between the three groups; however, the bone age was significantly
      higher in the overweight and obesity groups than in the normal weight group
      (P<0.05). The peak level of LH in the GnRH agonist test and SHBG level in the
      normal weight group were significantly higher than those in the overweight and
      the obesity groups, while the serum levels of leptin and neurokinin B were
      significantly lower in the normal weight group than in the overweight and the
      obesity groups (P<0.05). BMI was negatively correlated with the peak level of LH
      in the GnRH agonist test and SHBG level (P<0.05), and positively correlated with
      the levels of leptin and neurokinin B (P<0.05). CONCLUSIONS: The effects of BMI
      on the result of the GnRH agonist test and levels of obesity-related hormones
      should be taken into account in girls with precocious puberty.

PMID- 26287334
TI  - Combinational Therapy Enhances the Effects of Anti-IGF-1R mAb Figitumumab to
      Target Small Cell Lung Cancer.
AB  - BACKGROUND: Small cell lung cancer (SCLC) is a recalcitrant malignancy with
      distinct biologic properties. Antibody targeting therapy has been actively
      investigated as a new drug modality. METHODS: We tested the expression of IGF-1R
      and calculated the survival in 61 SCLC patients. We also evaluated the anti-tumor
      effects of anti-IGF-1R monoclonal antibody Figitumumab (CP) on SCLC, and tried
      two drug combinations to improve CP therapy. RESULTS: Our clinical data suggested
      that high IGF-1R expression was correlated with low SCLC patient survival. We
      then demonstrated the effect of CP was likely through IGF-1R blockage and down
      regulation without IGF-1R auto-phosphorylation and PI3K/AKT activation. However,
      we observed elevated MEK/ERK activation upon CP treatment in SCLC cells, and this
      MEK/ERK activation was enhanced by beta-arrestin1 knockdown while attenuated by
      beta-arrestin2 knockdown. We found both MEK/ERK inhibitor and metformin could
      enhance CP treatment in SCLC cells. We further illustrated the additive effect of
      metformin was likely through promoting further IGF-1R down-regulation.
      CONCLUSION: Our results highlighted the potential of anti-IGF-1R therapy and the
      adjuvant therapy strategy with either MEK/ERK inhibitor or metformin to target
      SCLC, warranting further studies.

PMID- 26287336
TI  - [Relationship of genotypes with clinical phenotypes and outcomes in children with
      cobalamin C type combined methylmalonic aciduria and homocystinuria].
AB  - OBJECTIVE: To analyze mutation types, clinical features, and treatment outcomes
      of cobalamin C (cblC) type combined methylmalonic aciduria and homocystinuria
      (MMA-HC) and to investigate the relationship of genotypes with clinical
      phenotypes and outcomes. METHODS: The clinical data of 16 Chinese children
      diagnosed with cblC type MMA-HC by gene analysis were retrospectively analyzed.
      According to the onset age, the patients were classified into early onset (<=1
      year) and late onset (>1 year). According to the clinical phenotype, the patients
      were classified into mild, moderate, and severe groups. All the patients were
      treated with vitamin B12 (cyanocobalamin) or hydroxocobalamin, betaine, folate,
      vitamin B6, and L-carnitine. RESULTS: Fifteen patients belonged to the early
      onset type, including 11 in the severe group and 4 in the moderate group. The
      remaining one belonged to the late onset type. Seven reported mutations and two
      novel mutations (c.445_446delTG and c.349G>c) were detected. The c.609G>A and
      c.658_660delAAG were the most common mutations detected in 13 (81%) out of 16
      patients. The genotype caused by compound heterozygous mutations of these two
      alleles (c.609 G>A/c.658_660delAAG) was the most common in the patients, detected
      in 4 (25%) out of 16 patients. Patients with this genotype had severe
      microcephaly and eye diseases and these clinical manifestations were not improved
      after the treatment. The patient with late-onset cblC type MMA-HC had normal
      clinical phenotypes after treatment. In the 15 early onset patients, the more
      severe the clinical phenotype, the worse the treatment outcome. CONCLUSIONS: The
      cblC type MMA-HC mainly manifests as early onset in China and c.609G >A and
      c.658_660delAAG are the most common mutations causing this disease. The clinical
      phenotypes are associated with the outcomes in children with cblC type MMA-HC.

PMID- 26287337
TI  - [Identification of a novel pathogenic mutation in PDHA1 gene for pyruvate
      dehydrogenase complex deficiency].
AB  - OBJECTIVE: To study the molecular genetic mechanism and genetic diagnosis of
      pyruvate dehydrogenase complex deficiency (PHD), and to provide a basis for
      genetic counseling and prenatal genetic diagnosis of PHD. METHODS: Polymerase
      chain reaction (PCR) was performed to amplify the 11 exons and exon junction of
      the PDHA1 gene from a child who was diagnosed with PHD based on clinical
      characteristics and laboratory examination results. The PCR products were
      sequenced to determine the mutation. An analysis of amino acid conservation and
      prediction of protein secondary and tertiary structure were performed using
      bioinformatic approaches to identify the pathogenicity of the novel mutation.
      RESULTS: One novel duplication mutation, c.1111_1158dup48bp, was found in the
      exon 11 of the PDHA1 gene of the patient. No c.1111_1158dup48bp mutation was
      detected in the sequencing results from 50 normal controls. The results of
      protein secondary and tertiary structure prediction showed that the novel
      mutation c.1111 _1158dup48bp led to the duplication of 16 amino acids residues,
      serine371 to phenylalanine386, which induced a substantial change in protein
      secondary and tertiary structure. The conformational change was not detected in
      the normal controls. CONCLUSIONS: The novel duplication mutation
      c.1111_1158dup48bp in the PDHA1 gene is not due to gene polymorphisms but a
      possible novel pathogenic mutation for PHD.

PMID- 26287338
TI  - [Glucocorticoid combined with ulinastatin in treatment of Kawasaki disease in
      children: a non-randomized controlled clinical trial].
AB  - OBJECTIVE: To investigate the clinical efficacy of glucocorticoid combined with
      ulinastatin in the treatment of Kawasaki disease (KD) in children. METHODS: A
      total of 104 children who were admitted and diagnosed with typical KD between
      January 2011 and December 2013 were assigned to ulinastatin group
      (methylprednisolone+ulinastatin; n=46) and intravenous immunoglobulin (IVIG)
      group (n=58) according to the severity of KD and the willingness of their
      parents. Observations for the two groups were performed to compare the changes in
      coronary artery diameter before and at 1 week, 3 months, and 6 months after
      treatment, fever clearance time, retreatment condition, changes in white blood
      cells (WBC), platelets (PLT), hemoglobin (HB), C-reactive protein (CRP), and
      erythrocyte sedimentation rate (ESR) at 1 week and 3 weeks after treatment, and
      total in-hospital cost. RESYLTS: There was no significant difference in the
      coronary artery diameter between the two groups before or at 1 week, 3 months or
      6 months after treatment (P>0.05). All the patients (100%) in the ulinastatin
      group vs 83% in the IVIG group had a normal body temperature after 48 hours of
      treatment (P<0.01). Two patients (4%) in the ulinastatin group and 10 patients
      (17%) in the IVIG group received retreatment. Significant differences were
      observed in ESR, WBC, and HB between them (P<0.01). The total in-hospital cost in
      the ulinastatin group was significantly lower than that in the IVIG group
      (P<0.01). CONCLUSIONS: For children with KD, methylprednisolone combined with
      ulinastatin does not increase the risk of coronary artery aneurysm, decreases in
      hospital costs, is superior in controlling laboratory markers and shortening the
      duration of fever during the acute phase compared with the IVIG therapy.

PMID- 26287339
TI  - [Clinical characteristics of children with an initial onset of IgA nephropathy
      with nephrotic syndrome].
AB  - OBJECTIVE: To study the clinical characteristics of children with an initial
      onset of IgA nephropathy with nephrotic syndrome and compare them with children
      with primary nephrotic syndrome, in order to provide a theoretical basis for the
      differential diagnosis of the two diseases. METHODS: Fifty children diagnosed
      with an initial onset of IgA nephropathy with nephrotic syndrome were included in
      this study. Seventy-two children diagnosed with an initial onset of primary
      nephrotic syndrome served as the control group. The clinical and laboratory
      examination characteristics were compared between the two groups. RESULTS: The
      IgA nephropathy group had significantly higher incidence rates of gross
      haematuria, microscopic haematuria, hypertension, acute kidney injury, low serum
      high-density lipoprotein cholesterol, anemia, low serum complement C4, steroid
      resistance, and nephritis-type nephrotic syndrome and a significantly lower
      incidence of elevated serum IgE compared with the control group (P<0.05). There
      were significant differences in serum creatinine, serum uric acid, serum total
      cholesterol, serum high-density lipoprotein cholesterol, serum IgE, serum
      complement C4, and hemoglobin levels between the IgA nephropathy and the control
      groups (P<0.05). The thresholds of serum IgE (<131.2 IU/mL) and high-density
      lipoprotein cholesterol (<1.35 mmol/L) were reference parameters in the
      differential diagnosis of IgA nephropathy with nephrotic syndrome and primary
      nephrotic syndrome. CONCLUSIONS: Children with IgA nephropathy presenting
      nephrotic syndrome manifest mainly as nephritis type and steroid-resistant type
      in the clinical classification. Cinical manifestations accompanied by serum
      levels of high-density lipoprotein cholesterol and IgE are helpful for
      differential diagnosis of IgA nephropathy presenting nephrotic syndrome and
      primary nephrotic syndrome.

PMID- 26287340
TI  - [Expression and clinical significance of serum high-mobility group protein box 1
      in children with Henoch-Schonlein purpura].
AB  - OBJECTIVE: To determine the expression of high-mobility group protein box 1
      (HMGB1), high-sensitivity C-reactive protein (hs-CRP), and D-dimer (D-D) in the
      peripheral blood of children with Henoch-Schonlein purpura (HSP) and to
      investigate the clinical significance of HMGB1 in children with HSP. METHODS: A
      total of 40 children with HSP (HSP group) and 30 healthy children (control group)
      were involved in the study. The level of serum HMGB1 was determined using enzyme
      linked immunosorbent assay, and the levels of serum hs-CRP and plasma D-D were
      determined using automatic biochemical analyzer and automatic blood coagulation
      analyzer, respectively. RESULTS: The levels of HMGB1, hs-CRP, and D-D in the
      peripheral blood of the HSP group in the acute phase were significantly higher
      than in the control group (P<0.05). The levels of the three indicators were
      significantly higher in HSP children with renal damage than in those without
      renal damage (P<0.05). In children with HSP, the expression of HMGB1 was
      positively correlated with the expression of hs-CRP and D-D (r=0.878, P<0.001;
      r=0.625, P<0.001). CONCLUSIONS: The expression of HMGB1 is related to the
      inflammatory response and hypercoagulability in children with HSP. HMGB1 may be
      involved in the development of HSP and associated renal damage in children.

PMID- 26287341
TI  - [Effects of hemoperfusion treatment on serum IL-23 and IL-17 levels in children
      with Henoch-Schonlein purpure].
AB  - OBJECTIVE: To study the effects of hemoperfusion treatment on serum interleukin
      17 (IL-17) and IL-23 levels in children with Henoch-Schonlein purpura (HSP).
      METHODS: Eighty-seven children who were diagnosed with HSP and who had received
      hemoperfusion treatment between January 2011 and December 2012 were enrolled.
      Twenty-seven sex- and age-matched healthy children were recruited as normal
      controls. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum
      concentrations of IL-17 and IL-23. RESULTS: The serum IL-23 and IL-17 levels in
      the HSP group were significantly higher than in the control group (P<0.05). After
      hemoperfusion treatment, the serum IL-23 and IL-17 levels in the HSP group were
      significantly reduced to the levels of the control group. Serum serum IL-17 level
      was positively correlated with serum IL-23 level (P<0.05) in children with HSP.
      CONCLUSIONS: Hemoperfusion treatment can reduce serum IL-23 and IL-17 levels in
      children with HSP, suggesting that the treatment may be effective for HSP.

PMID- 26287342
TI  - [Diagnostic values of fractional exhaled nitric oxide for typical bronchial
      asthma and cough variant asthma in children].
AB  - OBJECTIVE: To study the diagnostic values of fractional exhaled nitric oxide
      (FeNO) for typical bronchial asthma and cough variant asthma in children, and to
      explore whether FeNO can be applied to differentiate typical bronchial asthma
      from cough variant asthma in children. METHODS: A total of 150 children who were
      newly diagnosed with typical bronchial asthma between June 2012 and June 2014, as
      well as 120 children who were newly diagnosed with cough variant asthma during
      the same period, were selected as subjects. FeNO measurement, spirometry, and
      methacholine provocation test were performed for both groups. Meanwhile, 150
      healthy children were selected as the control group, and their FeNO was measured.
      The diagnostic values of FeNO for typical bronchial asthma and cough variant
      asthma were analyzed using the receiver operating characteristic curve. RESULTS:
      The FeNO values in the typical bronchial asthma and cough variant asthma groups
      were significantly higher than in the control group (P<0.01), and the FeNO value
      in the typical bronchial asthma group was significantly higher than in the cough
      variant asthma group (P<0.01). FEV1/FVC%, FEV1%pred, and PD20 were significantly
      lower in the typical bronchial asthma group than in the cough variant asthma
      group (P<0.01). The optimal cut-off value of FeNO was 19.5 ppb for the diagnosis
      of typical bronchial asthma, with a sensitivity of 83.3% and a specificity of
      86.7%; the optimal cut-off value of FeNO was 15.5 ppb for the diagnosis of cough
      variant asthma, with a sensitivity of 67.5% and a specificity of 78.0%; the
      optimal cut-off value of FeNO was 28.5 ppb for the differentiation between
      typical bronchial asthma and cough variant asthma, with a sensitivity of 60.7%
      and a specificity of 82.5%. CONCLUSIONS: Measurenment of FeNO may be useful in
      the diagnosis and differential diagnosis of typical bronchial asthma and cough
      variant asthma.

PMID- 26287343
TI  - [Association between serum allergens and asthma in children].
AB  - OBJECTIVE: To study the association between serum-specific immunoglobulin E
      (sIgE) allergens and asthma in children. METHODS: The serum sIgE allergens were
      determined using Western blot in 2239 children aged 1-14 years, consisting of
      1415 children with asthma alone and 824 children with non-allergic diseases
      between December 2004 and April 2013. The case-control models of asthma alone and
      non-allergic diseases were established. The association between allergens and
      asthma was investigated using multivariate logistic regression analysis. RESULTS:
      In the 2239 children, 1028 children (45.91%) were serum sIgE-positive, and the
      allergen with the highest positive rate was house-dust mite (15.68%), followed by
      house dust (14.29%) and moulds (13.40%). The results of the case-control analysis
      showed that house-dust mite, moulds, house dust, and cashew nut/peanut/soybean
      were significantly associated with the development of asthma. House dust was
      associated with the development of asthma in the 1-2 years old group (P<0.05).
      House dust and house-dust mite as allergens were identified as the risk factors
      for the development of asthma in the 3-14 years old group (P<0.05). In the 6-14
      years old group, moulds as allergens were identified as the risk factors for the
      development of asthma (P<0.05). House dust and house-dust mite as allergens
      increased the risk of asthma in boys and girls, while moulds and cashew
      nuts/peanuts/soybeans as allergens increased the risk of asthma in boys.
      CONCLUSIONS: House-dust mite, house dust, and moulds are the most common
      allergens in children with asthma, and they are closely associated with the
      development of asthma.

PMID- 26287344
TI  - [Association between ZNF365 gene polymorphisms and bronchial asthma in children].
AB  - OBJECTIVE: To study the association of single nucleotide polymorphisms (SNP)
      (rs2393903 and rs10995251) in ZNF365 gene with bronchial asthma and its clinical
      characteristics in Han Chinese children in Hubei, China. METHODS: A total of 221
      children with bronchial asthma and 243 normal children, all of whom were from
      Hubei, were recruited to carry out a case-control study. The genotype and allele
      frequencies of two SNPs in ZNF365 gene were determined using the polymerase chain
      reaction-restriction fragment length polymorphism technique. RESULTS: There were
      no significant differences in the distribution of three genotypes (GG, GA, AA)
      and allele frequency in SNP rs2393903 between the asthma and control groups
      (P>0.05). However, there were significant differences in the distribution of
      three genotypes (CC, CT, TT) and allele frequency in SNP rs10995251 between the
      asthma and control groups (P<0.05); C allele was a risk factor (OR=1.380). The
      asthmatic children with CC genotype of SNP rs10995251 had a significantly higher
      serum level of total immunoglobulin E (IgE) than those with TT genotype (P<0.05).
      CONCLUSIONS: The SNP rs10995251 in ZNF365 gene is associated with the
      susceptibility to bronchial asthma in children in Hubei, China, and the SNP may
      affect the level of serum IgE in these children.

PMID- 26287345
TI  - [Changes in serum inflammatory factors in wheezing infants with community
      acquired pneumonia].
AB  - OBJECTIVE: To study whether infantile wheezing pneumonia has similar immune
      mechanisms to asthma by determining the levels of serum inflammatory factors in
      wheezing infants with community-acquired pneumonia (CAP). METHODS: Forty-two
      infants with CAP but without wheezing, 47 infants with CAP and wheezing, and 30
      healthy infants as a control were recruited in the study. The peripheral blood
      levels of C-reactive protein, procalcitonin, soluble triggering receptor
      expressed on myeloid cell-l, interferon-gamma, interleukin-4, interleukin-10, and
      periostin were compared in the three groups. RESULTS: The serum levels of
      procalcitonin, soluble triggering receptor expressed on myeloid cell-l,
      interleukin-4 and interleukin-10 in the two CAP groups were higher than in the
      control group (P<0.05). The ratio of interferon-gamma/interleukin-4 in the
      wheezing pneumonia group was lower than in the non-wheezing pneumonia and control
      groups (P<0.05). The serum level of periostin in the wheezing pneumonia group was
      higher than in the non-wheezing pneumonia and control groups (P<0.05).
      CONCLUSIONS: The unbalanced ratio of interferon-gamma/interleukin-4 and airway
      eosinophilic inflammation in wheezing infants with pneumonia suggest infantile
      pneumonia with wheezing may has similar immune mechanisms to asthma.

PMID- 26287346
TI  - [Efficacy and safety of imatinib for the treatment of Philadelphia chromosome
      positive acute lymphoblastic leukemia in children].
AB  - OBJECTIVE: To study the efficacy and safety of Chinese Childhood Leukemia Group
      ALL 2008 (CCLG-ALL2008) protocol combined with tyrosine kinase inhibitor (TKI,
      imatinib) for the treatment of Philadelphia chromosome-positive (Ph+) acute
      lymphoblastic leukemia (ALL) in children. METHODS: The clinical data of 53
      patients aged less than 15 years when first diagnosed with Ph+ ALL between
      October 2008 and December 2013 were retrospectively analyzed. The patients were
      assigned to two groups: HR (n=26) and HR+TKI (n=27). The HR group was treated
      with CCLG-ALL2008 protocol (for high-risk patients). The HR+TKI group was treated
      with imatinib in combination with CCLG-ALL2008 protocol (for high-risk patients).
      RESULTS: The complete remission rate and chemotherapy induction-related mortality
      rate in the TKI+HR and HR groups were 100% vs 75% and 0 vs 15%, respectively. The
      3-year event-free survival (EFS) rate in the HR group was (6+/-5)%; the 5-year
      EFS rate of the TKI+HR group was (52+/-11)%. Compared with the HR group, the
      TKI+HR group had no increase in the toxic responses to chemotherapy and had a
      decrease in the infection rate during the induction period. CONCLUSIONS:
      Application of imatinib significantly improves the clinical efficacy in children
      with Ph+ ALL and has good safety.

PMID- 26287347
TI  - [Expression of CD58 in childhood B-lineage acute lymphoblastic leukemia and its
      feasibility in minimal residual disease detection].
AB  - OBJECTIVE: To measure the expression of lymphocyte function-associated antigen-3
      (CD58) in childhood B-lineage acute lymphoblastic leukemia (B-ALL) and to explore
      the feasibility of CD58 as an indicator for minimal residual disease (MRD)
      detection in childhood B-ALL. METHODS: Eighty-seven children diagnosed with B-ALL
      between January 2014 and September 2014 were enrolled, and 20 hospitalized
      children who had no tumor or blood disease and had normal bone marrow cell
      morphology served as the control group. The expression features of CD58 in bone
      marrow samples from the two groups (at diagnosis, on day 15 of induction
      chemotherapy) were analyzed by four-color flow cytometry (FCM). Quantitative real
      time polymerase chain reaction (qRT-PCR) and FCM were used to detect MRD in B-ALL
      patients on day 33 of induction chemotherapy. RESULTS: The mean fluorescence
      intensity of CD58 expression in the 87 B-ALL cases (91+/-33) was significantly
      higher than that in the 20 controls (14+/-6) (P<0.01); CD58 was over-expressed in
      44 of the B-ALL cases. In the B-ALL children, the expression of CD58 on day 15 of
      induction chemotherapy (105+/-22) was not significantly different from that at
      diagnosis (107+/-26) (P>0.05). In the 44 B-ALL patients with CD58 over
      expression, FCM showed 9 MRD(+) cases and 35 MRD(-) cases, while qRT-PCR showed
      11 MRD(+) cases and 33 MRD(-) cases; 42 cases (95%) showed consistent results of
      the two tests, so there was no significant difference between the two methods in
      detecting MRD (P>0.05). CONCLUSIONS: CD58 is over-expressed and stable in
      children with B-ALL, and it can be considered as an indicator for MRD detection
      in childhood B-ALL.

PMID- 26287348
TI  - [Risk factors for iron deficiency anemia in infants aged 6 to 12 months and its
      effects on neuropsychological development].
AB  - OBJECTIVE: To study the risk factors for moderate and severe iron deficiency
      anemia (IDA) in infants aged 6-12 months, and to preliminarily investigate the
      effects of IDA on the neuromotor development and temperament characteristics of
      infants. METHODS: A total of 326 infants aged 6-12 months with IDA were
      classified into three groups: mild IDA (n=176), moderate IDA (n=111), and severe
      IDA (n=39) according to the severity of anemia. The risk factors for moderate or
      severe IDA were investigated by multivariate logistic regression analysis. Three
      hundred and forty-six infants without IDA who showed matched age, sex, and other
      backgrounds were selected as the control group. The Gesell Development Diagnosis
      Scale was used to evaluate children's mental development. The Temperament Scale
      for infants was used for evaluating children's temperament. RESULTS: The
      univariate analysis showed that the severity of IDA was associated with sex,
      birth weight, gestational age, multiple birth, maternal anemia during pregnancy,
      and mother's lack of knowledge about IDA (P<0.05). Setting the mild IDA group as
      control, the multivariate logistic regression analysis showed that multiple
      birth, premature birth, low birth weight (<2500 g), maternal anemia during
      pregnancy, breast feeding, and mother's lack of knowledge about IDA were the risk
      factors for severe IDA (OR>1; P<0.05); premature birth, breast feeding, and mixed
      feeding were the risk factors for moderate IDA (OR>1; P<0.05). The IDA group had
      significantly lower scores in Gesell general development quotient, gross motor,
      adaptive behavior, and fine motor than the control group (P<0.05). The IDA group
      had higher percentages of children with difficulty and intermediate difficulty
      temperaments than the control group (P<0.05). The IDA group had significantly
      higher scores in activity level, rhythmicity, adaptability, and perseverance than
      the control group (P<0.05). CONCLUSIONS: The severity of IDA is associated with
      premature birth, multiple birth, low birth weight, feeding pattern, maternal
      anemia during pregnancy and mother's lack of knowledge about IDA in infants aged
      6-12 months. Infants with IDA have delayed neuromotor development and most of
      them have negative temperaments. More attention should be paid to mental and
      behavior problems for the infants. It is necessary to provide guidance for their
      parents in feeding and education.

PMID- 26287349
TI  - [Serum levels of 25-hydroxyvitamin D in children with attention deficit
      hyperactivity disorder].
AB  - OBJECTIVE: To examine serum 25-hydroxyvitamin D levels in children with attention
      deficit hyperactivity disorder (ADHD) and to explore the relationship between
      vitamin D level and ADHD. METHODS: Ninety-seven children with ADHD who were
      diagnosed according to DSM-V were selected as the ADHD group, including 46 cases
      of ADHD-I, 10 cases of ADHD-HI, and 41 cases of ADHD-C. Ninety-seven healthy
      children served as the control group. Serum levels of 25-hydroxyvitamin D were
      measured using electrochemiluminescence immunoassay. RESULTS: Mean serum levels
      of 25-hydroxyvitamin D in the ADHD group (17+/-7 ng/mL) were significantly lower
      than in the control group (23+/-8 ng/mL; P<0.01). The serum levels of 25
      hydroxyvitamin D in the three subtypes groups of ADHD (ADHD-I, ADHD-HI, and ADHD
      C) were all lower than in the control group (P<0.05). The rates of vitamin D
      insufficiency, deficiency or normal in the ADHD group were different from the
      control group (P<0.01). The distributions of vitamin D levels in the three
      subtypes groups of ADHD were all different from the control group (P<0.05).
      CONCLUSIONS: Serum levels of 25-hydroxyvitamin D in children with ADHD are lower
      than in healthy children, suggesting vitamin D level might be related to ADHD.

PMID- 26287350
TI  - [Correlation between growth rate of corpus callosum and neuromotor development in
      preterm infants].
AB  - OBJECTIVE: To investigate the growth rate of corpus callosum by cranial
      ultrasound in very low birth weight preterm infants and to provide a reference
      for early evaluation and improvement of brain development. METHODS: A total of
      120 preterm infants under 33 weeks' gestation were recruited and divided into 26
      29(+6) weeks group (n=64) and 30-32(+6) weeks group (n=56) according to the
      gestational age. The growth rate of corpus callosum was compared between the two
      groups. The correlation between the corpus callosum length and the cerebellar
      vermis length and the relationship of the growth rate of corpus callosum with
      clinical factors and the neuromotor development were analyzed. RESULTS: The
      growth rate of corpus callosum in preterm infants declined since 2 weeks after
      birth. Compared with the 30-32(+6) weeks group, the 26-29(+6) weeks group had a
      significantly lower growth rate of corpus callosum at 3-4 weeks after birth, at 5
      6 weeks after birth, and from 7 weeks after birth to 40 weeks of corrected
      gestational age. There was a positive linear correlation between the corpus
      callosum length and the cerebellar vermis length. Small-for-gestational age
      infants had a low growth rate of corpus callosum at 2 weeks after birth. The 12
      preterm infants with severe abnormal intellectual development had a lower growth
      rate of corpus callosum compared with the 108 preterm infants with non-severe
      abnormal intellectual development at 3-6 weeks after birth. The 5 preterm infants
      with severe abnormal motor development had a significantly lower growth rate of
      corpus callosum compared with the 115 preterm infants with non-severe abnormal
      motor development at 3-6 weeks after birth. CONCLUSIONS: The decline of growth
      rate of corpus callosum in preterm infants at 2-6 weeks after birth can increase
      the risk of severe abnormal neuromotor development.

PMID- 26287351
TI  - [Comparison of clinical efficacy of heated humidified high flow nasal cannula
      versus nasal continuous positive airway pressure in treatment of respiratory
      distress syndrome in very low birth weight infants].
AB  - OBJECTIVE: To compare the differences of clinical efficacy between heated
      humidified high-flow nasal cannula (HHHFNC) ventilation and nasal continuous
      positive airway pressure (NCPAP) in the treatment of respiratory distress
      syndrome (RDS) in very low birth weight (VLBW) infants. METHODS: A total of 66
      VLBW infants who were admitted to the neonatal intensive care unit were diagnosed
      with RDS, and they were randomly assigned to HHHFNC group and NCPAP group after
      receiving treatment with porcine pulmonary surfactant and conventional treatment.
      The changes in clinical symptoms and the incidence of complications were observed
      in the two groups. RESULTS: The HHHFN group had significantly earlier first milk
      feeding and full enteral feeding, significantly shorter oxygen exposure time and
      invasive ventilation time, and significantly lower incidences of second
      intubation within 7 days, nasal injury, air leak, and abdominal distention, as
      compared with the NCPAP group. CONCLUSIONS: Compared with NCPAP, HHHFNC causes
      slighter injury and has better tolerability, and it can be considered as the
      first choice of noninvasive ventilation in the treatment of RDS in VLBW infants.

PMID- 26287352
TI  - [Prophylactic probiotics for preventing necrotizing enterocolitis and reducing
      mortality in very low birth weight infants: a Meta analysis].
AB  - OBJECTIVE: To systematically evaluate the efficacy and safety of probiotic
      supplementation for preventing necrotizing enterocolitis (NEC) and reducing
      mortality in preterm very low birth weight (VLBW) infants. METHODS: The
      randomized controlled trials (RCTs) about probiotics for preventing NEC in
      preterm neonates were searched in PubMed, EMbase, Cochrane Central Register of
      Controlled Trials (CENTRAL), the ISI Web of Knowledge databases, China Biology
      Medicine disc (CBM), China National Knowledge Infrastructure (CNKI), Weipu and
      Wanfang Data from their establishment to March 2014. The Cochrane Collaboration's
      RevMan 5.1 Software was used for a Meta analysis. RESULTS: A total of 21 RCTs
      involving 4 607 preterm VLBW infants were eligible for inclusion in the Meta
      analysis. The Meta analysis showed that probiotic supplement was associated with
      a significantly decreased risk of NEC in preterm VLBW infants (RR=0.47; 95%CI:
      0.35-0.62; P<0.001). Risk of mortality was also significantly reduced in the
      probiotic group (RR=0.63; 95%CI: 0.51-0.78; P<0.01). Probiotic supplement did not
      decrease the risk for sepsis (RR=0.87; 95%CI: 0.72-1.06; P=0.17) and NEC related
      mortality (RR=0.68; 95%CI: 0.31-1.48, P=0.33). CONCLUSIONS: The results confirm
      that probiotic supplement can reduce risk of NEC and mortality in preterm VLBW
      infants. However, the long-term effects and safety of probiotics need to be
      assessed in large trials.

PMID- 26287353
TI  - [A preliminary study of long-term mitochondrial dysfunction in rat brain caused
      by lipopolysaccharide-induced sepsis].
AB  - OBJECTIVE: To preliminarily investigate the long-term structural and functional
      injuries of mitochondria in rat brain caused by sepsis. METHODS: Wistar rats were
      randomly assigned into sepsis and control groups. A rat model of sepsis was
      prepared by an intraperitoneal injection of 10 mg/kg lipopolysaccharide (LPS) of
      gram-negative bacteria, and the survival assay was performed. Eight rats in the
      sepsis group were sacrificed at 12, 24, 48, or 72 hours after LPS injection,
      while rats in the control group were sacrificed after an intraperitoneal
      injection of an equal volume of normal saline. Mitochondria were extracted from
      rat brain tissue. Mitochondrial membrane potential (MMP) and mitochondrial
      swelling level were determined by flow cytometry, and the activities of electron
      transport chain complexes (I-V) were measured using enzyme assay kits.
      Hematoxylin-eosin (HE) staining and electron microscopy were used to observe
      morphological changes in brain tissue and mitochondria. RESULTS: The sepsis group
      had a significantly lower survival rate than the control group (P<0.01). The MMP
      and activities of electron transport chain complexes (I-V) in the sepsis group,
      which were significantly lower than those in the control group (P<0.05), were
      reduced to the lowest levels at 48 hours and partially recovered at 72 hours. The
      mitochondrial swelling level in the sepsis group, which was significantly higher
      than that in the control group (P<0.05), increased to the peak level at 48 hours
      and partially recovered at 72 hours. Hematoxylin and Eosin staining revealed
      substantial damages in the structure of brain tissue, and electron microscopy
      showed mitochondrial swelling, and vacuolization in a few mitochondria.
      CONCLUSIONS: In the rat model of LPS-induced sepsis, both structural and
      functional injuries are found in cerebral mitochondria, and achieve the peak
      levels probably at around 48 hours.

PMID- 26287354
TI  - [Effect of non-methylated CpG-ODN on serum TGF-beta and immune regulation in
      ovalbumin-sensitized young mice].
AB  - OBJECTIVE: To explore the effect of non-methylated cytosine-phosphate-guanine
      oligodeoxynucleotides (CpG-ODN) on serum transforming growth factor (TGF)-beta
      and immune regulation in ovalbumin (OVA)-sensitized young mice. METHODS: Thirty
      female BALB/c mice (2-3 weeks old) were randomly divided into control, model, and
      CpG-ODN intervention groups. A young mouse model of food allergy was established
      by OVA sensitization. Normal saline of the same volume was used for replacement
      in the control group. The mice in the intervention group were intraperitoneally
      injected with CpG-ODN solution 1 hour before every OVA sensitization. Allergic
      symptoms were observed and scored for each group. The jejunal tissue was
      histopathologically examined with hematoxylin-eosin staining. Serum OVA-IgE level
      was measured using ELISA. Serum concentrations of interleukin (IL)-4, interferon
      (IFN)-gamma, and TGF-beta were determined by CBA. RESULTS: Allergic symptoms were
      observed in the model group and the jejunal tissue showed the pathological
      characteristics of type I allergic reaction. The allergic symptom scores in the
      model and CpG-ODN intervention groups were significantly higher than in the
      control group (P<0.01). The serum levels of OVA-IgE, IL-4, and TGF-beta were
      significantly higher in the model group than in the control and CpG-ODN
      intervention groups (P<0.05). The CpG-ODN intervention group had significantly
      higher serum levels of OVA-IgE, IL-4, and TGF-beta than the control group
      (P<0.05). Compared with the control and CpG-ODN intervention groups, the model
      group had a significantly reduced IFN-gamma level (P<0.05). CONCLUSIONS: The
      serum TGF-beta level is increased in the young mouse model of OVA-sensitized food
      allergy and is involved in the allergy mechanism. Non-methylated CpG-ODN can
      reduce the serum TGF-beta level in sensitized young mice and play an
      immunoregulatory role in food allergy.

PMID- 26287355
TI  - [Therapeutic effects of human umbilical cord mesenchymal stem cell
      transplantation on acute graft versus host disease].

PMID- 26287356
TI  - [Magnetic resonance imaging study on undefined bright objects in the brain tissue
      of children with neurofibromatosis type 1].

PMID- 26287357
TI  - [Value of fiberoptic bronchoscopy in the etiological diagnosis of laryngeal
      stridor in neonates].

PMID- 26287358
TI  - [Efficiency of modified peritoneal dialysis for the treatment of acute kidney
      failure following cardiac surgery in neonates].

PMID- 26287359
TI  - [A case report of childhood primary gout].

PMID- 26287360
TI  - [Research advances in the management of autism spectrum disorders in children].
AB  - Autism spectrum disorders (ASD) are a group of developmental dysfuntion of
      nervous system characterized by social interaction and communication disorders,
      restricted interests and repetitive stereotyped behaviors. The incidence of ASD
      has been increasing through the world. Some studies have shown that early
      reasonable individualized comprehensive intervention can obviously improve the
      prognosis of children with ASD. The etiology of ASD is unclear now, and
      behavioral and developmental intervention is the main therapy for ASD. The
      reasonable application of some drugs can improve the efficacy of the behavioral
      intervention for concomitant symptoms in ASD. With the in-depth study of the
      pathogenesis of ASD, bumetanide, oxytocin, vitamin D and hyperbaric oxygen
      therapy have been found to be promising for the improvement of core symptoms of
      ASD. This article reviews the research advances in the behavioral and
      developmental intervention and drug therapy for ASD. 

PMID- 26287361
TI  - In Situ Mass Spectrometric Determination of Molecular Structural Evolution at the
      Solid Electrolyte Interphase in Lithium-Ion Batteries.
AB  - Dynamic structural and chemical evolution at solid-liquid electrolyte interface
      is always a mystery for a rechargeable battery due to the challenge to directly
      probe a solid-liquid interface under reaction conditions. We describe the
      creation and usage of in situ liquid secondary ion mass spectroscopy (SIMS) for
      the first time to directly observe the molecular structural evolution at the
      solid-liquid electrolyte interface for a lithium (Li)-ion battery under dynamic
      operating conditions. We have discovered that the deposition of Li metal on
      copper electrode leads to the condensation of solvent molecules around the
      electrode. Chemically, this layer of solvent condensate tends to be depleted of
      the salt anions and with reduced concentration of Li(+) ions, essentially leading
      to the formation of a lean electrolyte layer adjacent to the electrode and
      therefore contributing to the overpotential of the cell. This observation
      provides unprecedented molecular level dynamic information on the initial
      formation of the solid electrolyte interphase (SEI) layer. The present work also
      ultimately opens new avenues for implanting the in situ liquid SIMS concept to
      probe the chemical reaction process that intimately involves solid-liquid
      interface, such as electrocatalysis, electrodeposition, biofuel conversion,
      biofilm, and biomineralization. 

PMID- 26287362
TI  - Routinized Assessment of Suicide Risk in Clinical Practice: An Empirically
      Informed Update.
AB  - OBJECTIVE: Empirically informed suicide risk assessment frameworks are useful in
      guiding the evaluation and treatment of individuals presenting with suicidal
      symptoms. Joiner et al. (1999) formulated one such framework, which has provided
      a concise heuristic for the assessment of suicide risk. The purpose of this
      review is to ensure compatibility of this suicide risk assessment framework with
      the growing literature on suicide-related behaviors. METHODS: This review
      integrates recent literature on suicide risk factors and clinical applications
      into the existing model. Further, we present a review of risk factors not
      previously included in the Joiner et al. (1999) framework, such as the
      interpersonal theory of suicide variables of perceived burdensomeness, thwarted
      belongingness, and capability for suicide (Joiner, 2005; Van Orden et al., 2010)
      and acute symptoms of suicidality (i.e., agitation, irritability, weight loss,
      sleep disturbances, severe affective states, and social withdrawal). RESULTS:
      These additional indicators of suicide risk further facilitate the classification
      of patients into standardized categories of suicide risk severity and the
      critical clinical decision making needed for the management of such risk.
      CONCLUSIONS: To increase the accessibility of empirically informed risk
      assessment protocols for suicide prevention and treatment, an updated suicide
      risk assessment form and decision tree are provided.

PMID- 26287363
TI  - The ultrasonographic detection of follicular rupture at the time of intrauterine
      insemination: is it really decisive?
AB  - Our aim is to assess the impact of the ultrasonographic detection of follicular
      rupture on the intrauterine insemination success. A total of 313 women undergoing
      ovarian stimulation for intrauterine insemination were enrolled. Transvaginal
      ultrasonography was performed to check whether the dominant follicle had ruptured
      and according to that the patients were divided into two groups. The ultrasound
      detection of follicular rupture was observed in 156 patients (54%). The
      independent variables favoring follicular rupture were: Age (t: 7.646, p <
      0.0005), FSH value (t: -5.637, p < 0.0005), duration of infertility (t: -4.265, p
      < 0.0005), menstrual cycle length (t: -4.927, p < 0.0005). Moreover, the logistic
      regression analysis demonstrated that the predictive variables for follicular
      rupture were: FSH value (OR 1.7, CI 95% 1.3-2.3, p < 0.0005), duration of
      infertility (OR 2.6, CI 95% 1.6-4.2, p < 0.0005) and menstrual cycle length (OR
      2.4, CI 95% 1.7-3.4, p < 0.0005). Pregnancy occurred in 23 patients of the group
      A (14.7%) and in 22 patients of the group B (16.5%) without a significant
      difference (p = 0.6). The logistic regression analysis confirmed that neither the
      evidence of follicular rupture nor any other variables influenced the pregnancy
      rate. 

PMID- 26287364
TI  - Cutaneous Infection Caused by Plant Pathogen Colletotrichum gloeosporioides.

PMID- 26287366
TI  - Liquid interface evolution of polyhedral-like graphene.
AB  - Centrifugation of the graphene oxide mediated Pickering emulsion results in
      transforming spheroidal toluene droplets into irregular polyhedral shapes, which
      can be preserved into a solid three-dimensional polyhedral-like graphene oxide
      network featuring facets and sharp edges, using a freeze-drying strategy. 

PMID- 26287365
TI  - Histone Deacetylase Inhibitors Inhibit the Proliferation of Gallbladder Carcinoma
      Cells by Suppressing AKT/mTOR Signaling.
AB  - Gallbladder carcinoma is an aggressive malignancy with high mortality mainly due
      to the limited potential for curative resection and its resistance to
      chemotherapeutic agents. Here, we show that the histone deacetylase inhibitors
      (HDACIs) trichostatin-A (TSA) and suberoylanilide hydroxamic acid (SAHA) reduce
      the proliferation and induce apoptosis of gallbladder carcinoma cells by
      suppressing the AKT/mammalian target of rapamycin (mTOR) signaling. Gallbladder
      carcinoma SGC-996 cells were treated with different concentrations of TSA and
      SAHA for different lengths of time. Cell proliferation and morphology were
      assessed with MTT assay and microscopy, respectively. Cell cycle distribution and
      cell apoptosis were analyzed with flow cytometry. Western blotting was used to
      detect the proteins related to apoptosis, cell cycle, and the AKT/mTOR signaling
      pathway. Our data showed that TSA and SAHA reduced SGC-996 cell viability and
      arrested cell cycle at the G1 phase in a dose- and time-dependent manner. TSA and
      SAHA promoted apoptosis of SGC-996 cells, down-regulated the expression of cyclin
      D1, c-Myc and Bmi1, and decreased the phosphorylation of AKT, mTOR p70S6K1, S6
      and 4E-BP1. Additionally, the mTOR inhibitor rapamycin further reduced the cell
      viability of TSA- and SAHA-treated SGC-996 cells and the phosphorylation of mTOR,
      whereas the mTOR activator 1,2-dioctanoyl-sn-glycero-3-phosphate (C8-PA) exerted
      the opposite influence. Our results demonstrate that histone deacetylase
      inhibitors (HDACIs) suppress the proliferation of gallbladder carcinoma cell via
      inhibition of AKT/mTOR signaling. These findings offer a mechanistic rationale
      for the application of HDACIs in gallbladder carcinoma treatment. 

PMID- 26287367
TI  - Magnetotactic bacteria: nanodrivers of the future.
AB  - Magnetotactic bacteria (MTB) represent a heterogeneous group of Gram-negative
      aquatic prokaryotes with a broad range of morphological types, including
      vibrioid, coccoid, rod and spirillum. MTBs possess the virtuosity to passively
      align and actively swim along the magnetic field. Magnetosomes are the trademark
      nano-ranged intracellular structures of MTB, which comprise magnetic iron-bearing
      inorganic crystals enveloped by an organic membrane, and are dedicated organelles
      for their magnetotactic lifestyle. Magnetosomes endue high and even dispersion in
      aqueous solutions compared with artificial magnetites, claiming them as paragon
      nanomaterials. MTB and magnetosomes offer high technological potential in modern
      science, technology and medicines. This review focuses on the applicability of
      MTB and magnetosomes in various areas of modern benefits. 

PMID- 26287368
TI  - Microbial production of lactic acid: the latest development.
AB  - Lactic acid is an important platform chemical for producing polylactic acid (PLA)
      and other value-added products. It is naturally produced by a wide spectrum of
      microbes including bacteria, yeast and filamentous fungi. In general, bacteria
      ferment C5 and C6 sugars to lactic acid by either homo- or hetero-fermentative
      mode. Xylose isomerase, phosphoketolase, transaldolase, l- and d-lactate
      dehydrogenases are the key enzymes that affect the ways of lactic acid
      production. Metabolic engineering of microbial strains are usually needed to
      produce lactic acid from unconventional carbon sources. Production of d-LA has
      attracted much attention due to the demand for producing thermostable PLA, but
      large scale production of d-LA has not yet been commercialized. Thermophilic
      Bacillus coagulans strains are able to produce l-lactic acid from lignocellulose
      sugars homo-fermentatively under non-sterilized conditions, but the lack of
      genetic tools for metabolically engineering them severely affects their
      development for industrial applications. Pre-treatment of agriculture biomass to
      obtain fermentable sugars is a pre-requisite for utilization of the huge amounts
      of agricultural biomass to produce lactic acid. The major challenge is to obtain
      quality sugars of high concentrations in a cost effective-way. To avoid or
      minimize the use of neutralizing agents during fermentation, genetically
      engineering the strains to make them resist acidic environment and produce lactic
      acid at low pH would be very helpful for reducing the production cost of lactic
      acid.

PMID- 26287369
TI  - Thalamocortical interactions underlying visual fear conditioning in humans.
AB  - Despite a strong focus on the role of the amygdala in fear conditioning, recent
      works point to a more distributed network supporting fear conditioning. We aimed
      to elucidate interactions between subcortical and cortical regions in fear
      conditioning in humans. To do this, we used two fearful faces as conditioned
      stimuli (CS) and an electrical stimulation at the left hand, paired with one of
      the CS, as unconditioned stimulus (US). The luminance of the CS was rhythmically
      modulated leading to "entrainment" of brain oscillations at a predefined
      modulation frequency. Steady-state responses (SSR) were recorded by MEG. In
      addition to occipital regions, spectral analysis of SSR revealed increased power
      during fear conditioning particularly for thalamus and cerebellum contralateral
      to the upcoming US. Using thalamus and amygdala as seed-regions, directed
      functional connectivity was calculated to capture the modulation of interactions
      that underlie fear conditioning. Importantly, this analysis showed that the
      thalamus drives the fusiform area during fear conditioning, while amygdala
      captures the more general effect of fearful faces perception. This study confirms
      ideas from the animal literature, and demonstrates for the first time the central
      role of the thalamus in fear conditioning in humans.

PMID- 26287370
TI  - Production of lignosulfonate in NSSC-based biorefinery.
AB  - The spent liquor (SL) of a neutral sulfite semichemical (NSSC) pulping process
      contains a considerable amount of lignocelluloses and is treated in wastewater
      systems. The lignocelluloses, however, can be used for producing value-added
      products if they are isolated from the SL. In this article, solvent treatment
      (mixing acetone, ethanol, or isopropyl with SL) was used as a method for
      isolating lignosulfonate from SL. The maximum lignosulfonate removal was obtained
      via mixing isopropyl alcohol with SL at the weight ratio of 20/80, room
      temperature, and 5.7 pH. The results also showed that the molecular weight and
      anionic charge density of the precipitates were in the range of 5,000-70,000
      g/mol and 0.2-1.8 meq/g, respectively. Based on these results, a process was
      proposed for isolating lignosulfonate from SL and converting the NSSC process to
      an NSSC-based biorefinery.

PMID- 26287371
TI  - Risperidone and Risk of Gynecomastia in Young Men.
AB  - OBJECTIVE: The purpose of this study was to quantify the risk of gynecomastia
      with risperidone in adolescent and young adult males. METHODS: We created a
      cohort of males 15-25 years of age from the IMS LifeLink database, and conducted
      a case-control study within the cohort by identifying all new cases of
      gynecomastia. For each case, 10 controls were selected and matched to the cases
      by age, follow-up, and calendar times (cases and controls had the same follow up
      time and cohort entry date). Rate ratios (RR) for current use of risperidone were
      computed adjusting for potential confounding variables. RESULTS: First diagnosis
      of gynecomastia was made based on International Classification of Diseases, 9th
      revision (ICD-9) for gynecomastia. There were 401,924 males ages 15-25 in the
      primary cohort. There were 1556 cases of gynecomastia and 15,560 corresponding
      controls. Current users of risperidone had approximately four times the risk of
      developing gynecomastia than non-users (RR=3.91, 95% CI=2.01-7.62). When the
      analysis was stratified to children and adolescents (<=18 years of age) taking
      risperidone, the risk of gynecomastia was five times higher than for non-users
      (RR=5.44, 95% CI=1.50-19.74). CONCLUSIONS: Risperidone is associated with an
      increase with the risk of gynecomastia in adolescent and young adult males.

PMID- 26287372
TI  - Genetically engineered pigs as investigative and translational models in
      dermatology.

PMID- 26287373
TI  - Correction: Placental Fatty Acid Ethyl Esters Are Elevated with Maternal Alcohol
      Use in Pregnancies Complicated by Prematurity.

PMID- 26287374
TI  - P-Glycoprotein Induction Ameliorates Colistin Induced Nephrotoxicity in Cultured
      Human Proximal Tubular Cells.
AB  - The pathogenesis of colistin induced nephrotoxicity is poorly understood.
      Currently there are no effective therapeutic or prophylactic agents available.
      This study was aimed to determine the mechanism of colistin induced
      nephrotoxicity and to determine whether P-glycoprotein (P-gp) induction could
      prevent colistin induced nephrotoxicity. Colistin induced cell toxicity in
      cultured human proximal tubular cells in both dose and time dependent manner.
      Colistin provoked ROS in a dose dependent manner as measured by DCF-DA. To
      investigate apoptosis, caspase 3/7 activity was determined. Caspase 3/7 activity
      was increased dose dependently (25, 50, 100 MUg/ml) at 6 h. Autophagosome
      formation was assessed by measuring LC3- II/LC3-I ratio. The ratio of LC3-II to
      LC3- I was increased at 2 h (25 MUg/ml). Suppression of autophagosome formation
      increased colistin induced nephrotoxicity. The expression of P-gp and the cell
      toxicity was determined in colistin with or without dexamethasone (P-gp inducer)
      and verapamil (selective P-gp inhibitor). Colistin itself suppressed the
      expression of P-gp. P-gp expression and activity decreased colistin induced
      nephrotoxicity with dexamethasone treatment. In addition induced P-gp transporter
      was shown to improve the efflux effect on colistin treated HK2 cell line, which
      was demonstrated by calcein-AM fluorescence accumulation assay. The increased
      activity could be blocked by N-acetylcysteine. In conclusion, colistin induces
      nephrotoxicity by suppressing P-gp. Induction of P-gp could ameliorate colistin
      induced nephrotoxicity by decreasing apoptosis. 

PMID- 26287375
TI  - Lysosomal iron liberation is responsible for the vulnerability of brain
      microglial cells to iron oxide nanoparticles: comparison with neurons and
      astrocytes.
AB  - Iron oxide nanoparticles (IONPs) are used for various biomedical and
      neurobiological applications. Thus, detailed knowledge on the accumulation and
      toxic potential of IONPs for the different types of brain cells is highly
      warranted. Literature data suggest that microglial cells are more vulnerable
      towards IONP exposure than other types of brain cells. To investigate the
      mechanisms involved in IONP-induced microglial toxicity, we applied fluorescent
      dimercaptosuccinate-coated IONPs to primary cultures of microglial cells.
      Exposure to IONPs for 6 h caused a strong concentration-dependent increase in the
      microglial iron content which was accompanied by a substantial generation of
      reactive oxygen species (ROS) and by cell toxicity. In contrast, hardly any ROS
      staining and no loss in cell viability were observed for cultured primary
      astrocytes and neurons although these cultures accumulated similar specific
      amounts of IONPs than microglia. Co-localization studies with lysotracker
      revealed that after 6 h of incubation in microglial cells, but not in astrocytes
      and neurons, most IONP fluorescence was localized in lysosomes. ROS formation and
      toxicity in IONP-treated microglial cultures were prevented by neutralizing
      lysosomal pH by the application of NH4Cl or Bafilomycin A1 and by the presence of
      the iron chelator 2,2'-bipyridyl. These data demonstrate that rapid iron
      liberation from IONPs at acidic pH and iron-catalyzed ROS generation are involved
      in the IONP-induced toxicity of microglia and suggest that the relative
      resistance of astrocytes and neurons against acute IONP toxicity is a consequence
      of a slow mobilization of iron from IONPs in the lysosomal degradation pathway.

PMID- 26287377
TI  - Understanding the 7-Cys module amplification of C. neoformans metallothioneins:
      how high capacity Cu-binding polypeptides are built to neutralize host
      nutritional immunity.
AB  - Cryptococcus neoformans metallothioneins (MTs), CnMT1 and CnMT2, have been
      identified as essential infectivity and virulence factors of this pathogen. Both
      MTs are unusually long Cu-thioneins, exhibiting protein architecture and metal
      binding abilities compatible with the hypothesis of resulting from three and five
      tandem repetitions of 7-Cys motives, respectively, each of them folding into Cu5
      clusters. Through the study of the Zn(II)- and Cu(I)-binding capabilities of
      several CnMT1 truncated mutants, we show that a 7-Cys segment of CnMT1 folds into
      Cu5-species, of additive capacity when joined in tandem. All the obtained Cu
      complexes share practically similar architectural features, if judging by their
      almost equivalent CD fingerprints, and they also share their capacity to restore
      copper tolerance in MT-devoid yeast cells. Besides the analysis of the modular
      composition of these long fungal MTs, we evaluate the features of the Cys-rich
      stretch spacer and flanking sequences that allow the construction of stable metal
      clusters by adjacent union of binding modules. Overall, our data support a
      mechanism by which some microbial MTs may have evolved to enlarge their original
      metal co-ordination capacity under the specific selective pressure of
      counteracting the Cu-based immunity mechanisms evolved by the infected hosts.

PMID- 26287376
TI  - Race, Ethnicity and Ancestry in Unrelated Transplant Matching for the National
      Marrow Donor Program: A Comparison of Multiple Forms of Self-Identification with
      Genetics.
AB  - We conducted a nationwide study comparing self-identification to genetic ancestry
      classifications in a large cohort (n = 1752) from the National Marrow Donor
      Program. We sought to determine how various measures of self-identification
      intersect with genetic ancestry, with the aim of improving matching algorithms
      for unrelated bone marrow transplant. Multiple dimensions of self-identification,
      including race/ethnicity and geographic ancestry were compared to classifications
      based on ancestry informative markers (AIMs), and the human leukocyte antigen
      (HLA) genes, which are required for transplant matching. Nearly 20% of responses
      were inconsistent between reporting race/ethnicity versus geographic ancestry.
      Despite strong concordance between AIMs and HLA, no measure of self
      identification shows complete correspondence with genetic ancestry. In certain
      cases geographic ancestry reporting matches genetic ancestry not reflected in
      race/ethnicity identification, but in other cases geographic ancestries show
      little correspondence to genetic measures, with important differences by gender.
      However, when respondents assign ancestry to grandparents, we observe sub-groups
      of individuals with well- defined genetic ancestries, including important
      differences in HLA frequencies, with implications for transplant matching. While
      we advocate for tailored questioning to improve accuracy of ancestry
      ascertainment, collection of donor grandparents' information will improve the
      chances of finding matches for many patients, particularly for mixed-ancestry
      individuals. 

PMID- 26287378
TI  - Viral etiology, clinical and laboratory features of adult hemophagocytic
      lymphohistiocytosis.
AB  - Secondary hemophagocytic lymphohistiocytosis (SHLH) is a potentially fatal
      hyperinflammatory syndrome with a heterogeneous etiology and has nonspecific
      clinical and laboratory findings. The diagnosis and treatment of adult SHLH is
      challenging because the etiology of the disease is difficult to identify, and the
      majority of reported cases are pediatric patients. The aim of this study was to
      describe the etiology, clinical characteristics, and outcomes of adult SHLH.
      Fifty-four adult patients who fulfilled the criteria of SHLH were enrolled in the
      study. Viral etiology, blood biomarkers, and clinical manifestations of SHLH were
      analyzed in these patients. Twenty-four SHLH patients had viraemia, whereas 30
      SHLH patients were secondary to other diseases. Epstein-Barr virus (EBV) was the
      most common virus that associated SHLH among all viruses studied. Severe SHLH
      patients with EBV-viraemia presented significantly high levels of ferritin,
      lactate dehydrogenase, aspartate transaminase (AST), and alanine transaminase
      (ALT). Positively relationships existed between EBV DNA titers and levels of AST
      and ALT (P < 0.05). The prognosis of SHLH patients with EBV viraemia was worse
      than that of non-EBV SHLH and non-viral SHLH. Our data reveal that EBV is the
      major pathogen in virus-associated SHLH, and EBV load influence disease
      development in SHLH patients with EBV infection that prognosis is worse than
      other viruses associated SHLH.

PMID- 26287381
TI  - Breakdown of Sensorimotor Network Communication in Leukoaraiosis.
AB  - BACKGROUND: Leukoaraiosis (LA) patients may suffer from sensorimotor
      dysfunctions. The relationship between behavioral disturbances and changes in the
      sensorimotor network (SMN) has not been thoroughly elucidated. OBJECTIVE: This
      study investigated the hypothesized breakdown of communication of SMN and its
      behavioral consequences in LA. METHODS: Fluid-attenuated inversion recovery
      (FLAIR) images, resting-state functional magnetic resonance images (fMRI) and
      behavioral data were collected from 30 LA patients and 26 healthy individuals
      (normal controls, NC). The subjects were grouped according to LA severity, as
      indicated by their FLAIR images. Group independent component analysis was applied
      to the fMRI data to map the functional connectivity of SMN for NC and LA
      patients. A whole-brain, voxel-wise analysis was employed to investigate the
      functional connectivity alteration of SMN in LA. The relationships between LA
      severity, functional connectivity alteration of the SMN and behavioral clinical
      symptoms were examined by correlation analysis. RESULTS: The right cingulate
      motor area (rCMA), left posterior insula and left ventral premotor area showed
      attenuated functional connectivity in the LA patients. The extent of the
      attenuation was related to the severity of the disease. Furthermore, the
      attenuation in the rCMA was associated with worse sensorimotor integration
      performance. CONCLUSIONS: These results suggest that LA impairs sensorimotor
      integration by interfering with the communication or coordination of these
      aforementioned regions related to the SMN.

PMID- 26287380
TI  - Assembly and Analysis of Differential Transcriptome Responses of Hevea
      brasiliensis on Interaction with Microcyclus ulei.
AB  - Natural rubber (Hevea brasiliensis) is a tropical tree used commercially for the
      production of latex, from which 40,000 products are generated. The fungus
      Microcyclus ulei infects this tree, causing South American leaf blight (SALB)
      disease. This disease causes developmental delays and significant crop losses,
      thereby decreasing the production of latex. Currently several groups are working
      on obtaining clones of rubber tree with durable resistance to SALB through the
      use of extensive molecular biology techniques. In this study, we used a secondary
      clone that was resistant to M. ulei isolate GCL012. This clone, FX 3864 was
      obtained by crossing between clones PB 86 and B 38 (H. brasiliensis x H.
      brasiliensis). RNA-Seq high-throughput sequencing technology was used to analyze
      the differential expression of the FX 3864 clone transcriptome at 0 and 48 h post
      infection (hpi) with the M. ulei isolate GCL012. A total of 158,134,220 reads
      were assembled using the de novo assembly strategy to generate 90,775 contigs
      with an N50 of 1672. Using a reference-based assembly, 76,278 contigs were
      generated with an N50 of 1324. We identified 86 differentially expressed genes
      associated with the defense response of FX 3864 to GCL012. Seven putative genes
      members of the AP2/ERF ethylene (ET)-dependent superfamily were found to be down
      regulated. An increase in salicylic acid (SA) was associated with the up
      regulation of three genes involved in cell wall synthesis and remodeling, as well
      as in the down-regulation of the putative gene CPR5. The defense response of FX
      3864 against the GCL012 isolate was associated with the antagonistic SA, ET and
      jasmonic acid (JA) pathways. These responses are characteristic of plant
      resistance to biotrophic pathogens. 

PMID- 26287379
TI  - Eye Movement Patterns in Natural Reading: A Comparison of Monolingual and
      Bilingual Reading of a Novel.
AB  - INTRODUCTION AND METHOD: This paper presents a corpus of sentence level eye
      movement parameters for unbalanced bilingual first language (L1) and second
      language (L2) reading and monolingual reading of a complete novel (56 000 words).
      We present important sentence-level basic eye movement parameters of both
      bilingual and monolingual natural reading extracted from this large data corpus.
      RESULTS AND CONCLUSION: Bilingual L2 reading patterns show longer sentence
      reading times (20%), more fixations (21%), shorter saccades (12%) and less word
      skipping (4.6%), than L1 reading patterns. Regression rates are the same for L1
      and L2 reading. These results could indicate, analogous to a previous simulation
      with the E-Z reader model in the literature, that it is primarily the speeding up
      of lexical access that drives both L1 and L2 reading development. Bilingual L1
      reading does not differ in any major way from monolingual reading. This contrasts
      with predictions made by the weaker links account, which predicts a bilingual
      disadvantage in language processing caused by divided exposure between languages.

PMID- 26287382
TI  - Fluctuating Behavior and Influential Factors in the Performance of the
      QuantiFERON-TB Gold In-Tube Assay in the Diagnosis of Tuberculosis.
AB  - BACKGROUND: The QuantiFERON-TB Gold In-Tube (QFT-GIT) is a newly developed but
      widely used interferon-gamma release assay for diagnosing tuberculosis (TB).
      However, research has not determined whether age or the use of an immune
      suppressive or anti-TB treatment influences this assay's ability to detect TB. We
      assessed the QFT-GIT diagnostic performance for active tuberculosis (ATB) in
      children and adults in an endemic country and explored the effects of
      glucocorticoids and anti-TB therapy on the diagnostic value of the QFT-GIT.
      METHODS: A total of 60 children and 212 adults with suspected ATB were evaluated
      with the QFT-GIT. The association between the QFT-GIT diagnostic value and
      pretreatment factors was qualitatively and quantitatively assessed. RESULTS: The
      sensitivity of the QFT-GIT was 83.9% (95% CI 66.3%-94.6%) in children, and 73.7%
      (95% CI 57.8%-85.2%) in adults. Glucocorticoids affected the mitogen-stimulated
      response in both children and adults. In subjects undergoing glucocorticoid
      pretreatment, 25.0% of the children presented with false-negative QFT-GIT
      results, 28.6% of adults presented with indeterminate results. For subjects pre
      treated with anti-TB drugs, 44.4% presented with false-negative QFT-GIT results.
      CONCLUSIONS: The QFT-GIT has higher sensitivity and specificity in children than
      adults. Glucocorticoid treatment negatively impacts the diagnostic value of the
      QFT-GIT in all age groups. Anti-TB treatment decreases the sensitivity of the QFT
      GIT. Therefore, we recommend that the QFT-GIT assay be performed before TB
      specific treatment is initiated and the test should not be used on people
      undergoing immunosuppression treatment, regardless of their age. A quantitative
      analysis of the QFT-GIT could be useful for assessing and monitoring TB-specific
      and non-specific immunity during conversion of the disease.

PMID- 26287383
TI  - Sex-specific lean body mass predictive equations are accurate in the obese
      paediatric population.
AB  - BACKGROUND: The clinical assessment of lean body mass (LBM) is challenging in
      obese children. A sex-specific predictive equation for LBM derived from
      anthropometric data was recently validated in children. AIM: The purpose of this
      study was to independently validate these predictive equations in the obese
      paediatric population. SUBJECTS AND METHODS: Obese subjects aged 4-21 were
      analysed retrospectively. Predicted LBM (LBMp) was calculated using equations
      previously developed in children. Measured LBM (LBMm) was derived from dual
      energy x-ray absorptiometry. Agreement was expressed as [(LBMm-LBMp)/LBMm] with
      95% limits of agreement. RESULTS: Of 310 enrolled patients, 195 (63%) were
      females. The mean age was 11.8 +/- 3.4 years and mean BMI Z-score was 2.3 +/-
      0.4. The average difference between LBMm and LBMp was -0.6% (-17.0%, 15.8%).
      Pearson's correlation revealed a strong linear relationship between LBMm and LBMp
      (r = 0.97, p < 0.01). CONCLUSION: This study validates the use of these
      clinically-derived sex-specific LBM predictive equations in the obese paediatric
      population. Future studies should use these equations to improve the ability to
      accurately classify LBM in obese children.

PMID- 26287384
TI  - Obstructions to Sampling Qualitative Properties.
AB  - BACKGROUND: Sampling methods have proven to be a very efficient and intuitive
      method to understand properties of complicated spaces that cannot easily be
      computed using deterministic methods. Therefore, sampling methods became a
      popular tool in the applied sciences. RESULTS: Here, we show that sampling
      methods are not an appropriate tool to analyze qualitative properties of
      complicated spaces unless RP = NP. We illustrate these results on the example of
      the thermodynamically feasible flux space of genome-scale metabolic networks and
      show that with artificial centering hit and run (ACHR) not all reactions that can
      have variable flux rates are sampled with variables flux rates. In particular a
      uniform sample of the flux space would not sample the flux variabilities
      completely. CONCLUSION: We conclude that unless theoretical convergence results
      exist, qualitative results obtained from sampling methods should be considered
      with caution and if possible double checked using a deterministic method.

PMID- 26287385
TI  - Syndiotactic Polystyrene/Hybrid Silica Spheres of POSS Siloxane Composites
      Exhibiting Ultralow Dielectric Constant.
AB  - Homogeneously dispersed hybrid silica/syndiotactic polystyrene composites were
      investigated for low-kappa dielectric applications. The composites were prepared
      by a solution blending method, and their microstructures were analyzed by SEM,
      TEM, and AFM. Crystallization and phase transformation behavior of sPS were
      investigated using differential scanning calorimetry and wide-angle X-ray
      diffraction. These composites exhibited improved thermal stability and reduced
      thermal expansion coefficients. Promising dielectric properties were observed for
      the composites in the microwave frequency region with a dielectric constant
      (kappa = 1.95) and loss (tan delta = 10(-4)) at 5 GHz. 

PMID- 26287387
TI  - Low-Bandgap Near-IR Conjugated Polymers/Molecules for Organic Electronics.

PMID- 26287386
TI  - Oral Health-Related Quality of Life and Traumatic Dental Injuries in Young
      Permanent Incisors in Brazilian Schoolchildren: A Multilevel Approach.
AB  - BACKGROUND: Traumatic dental injury (TDI) during childhood may negatively impact
      the quality of life of children. OBJECTIVE: To describe the association of oral
      health-related quality of life (OHRQoL) and domains (oral symptons, functional
      limitation, emotional- and social-well-being) of children with individual and
      contextual variables. METHODS: A cross-sectional study was performed using a
      representative sample of 1,201 schoolchildren, 8-10 years-old, from public and
      private schools of Belo Horizonte, Brazil. The CPQ8-10 was used to assess OHRQoL,
      dichotomized in low and high impact. Sociodemographic information was collected
      through questionnaires to parents. Children were examined at schools, using the
      Andreasen criteria. Individual variables were gender, age, number of residents in
      home, parents/caregivers' level of education, family income, and TDI
      (dichotomized into without trauma/mild trauma and severe trauma). Dental caries
      and malocclusion were considered co-variables. Contextual variables were the
      Social Vulnerability Index and type of school. Ethical approval and consent forms
      were obtained. Data were analyzed using SPSS for Windows 19.0 and HLM 6.06,
      including frequency distribution, chi-squared test and multilevel approach (p <
      0.05). RESULTS: The prevalence of a negative impact on OHRQoL in children with
      severe trauma was 55.9%. The TDI negatively impacted emotional and social domains
      of OHRQoL. A multilevel analysis revealed a significant difference in OHRQoL
      according to the type of school and showed that 16% of the total variance was due
      to contextual characteristics (p < 0.001; ICC = 0.16). The negative impact on
      OHRQoL was higher in girls (p = 0.009), younger children (p = 0.023), with severe
      TDI (p = 0.014), those from public schools (p = 0.017) and whose parents had a
      lower education level (p = 0.001). CONCLUSION: Severe trauma impacts OHRQoL on
      emotional and social domains. Contextual dimensions add information to individual
      variability to explain higher impact, emphasizing socioeconomic inequalities.

PMID- 26287389
TI  - Factors Contributing to Mental and Physical Health Care in a Disaster-Prone
      Environment.
AB  - Environment as a contextual factor plays an important role in southeastern
      Louisiana, as this area represents a major economic hub for the United States
      port, petroleum, and fishing industries. The location also exposes the population
      to both natural and technological disasters, including Hurricane Katrina and the
      Gulf oil spill. This study explored associations among hurricane loss, oil spill
      disruption, and environmental quality of life on mental and physical health on
      over 1,000 residents (N = 1,225) using structural equation modeling techniques.
      Results showed that oil spill distress was associated with increased symptoms of
      mental and physical health; Hurricane Katrina loss; and decreased environmental
      quality of life. Findings also indicate that mental health symptoms explain the
      association among oil spill distress and physical health symptoms-specifically,
      those that overlap with somatic complaints. These findings provide important
      support of the need for mental health assessment and service availability for
      disaster recovery. 

PMID- 26287388
TI  - Social participation of children age 8-12 with SLI.
AB  - PURPOSE: Two objectives are being pursued: (1) to describe the level of social
      participation of children aged 8-12 presenting a specific language impairment
      (SLI) and (2) to identify personal and family factors associated with their level
      of social participation. METHOD: This cross-sectional study was conducted among
      29 children with SLI and one of their parents. Parental stress and family
      adversity were measured as risk factors. The measure of life habits (LIFE-H)
      adapted to children aged 5-3 was used to measure social participation. RESULTS:
      The assumption that social participation of these children is impaired in
      relation to the communication dimension was generally confirmed. The statements
      referring to the "communication in the community" and "written communication" are
      those for which the results are weaker. "Communication at home" is made easier
      albeit with some difficulties, while "telecommunication" is totally preserved. A
      high level of parental stress is also confirmed, affecting the willingness of
      parents to support their child's autonomy. CONCLUSIONS: The achievement of a
      normal lifestyle of children with SLI is upset in many spheres of life. Methods
      of intervention must better reflect the needs and realities experienced by these
      children in their various living environments, in order to optimize social
      participation, and consequently, to improve their well-being and that of their
      families. The need to develop strategies to develop children's independence and
      to reduce parental stress must be recognized and all stakeholders need to be
      engaged in the resolution of this challenge. IMPLICATIONS FOR REHABILITATION: The
      realization of life habits of SLI children is compromised at various levels,
      especially in the domain related to "communication in the community" and "written
      communication". Speech-language pathologists must consider providing ongoing
      support throughout the primary years of these children and during adolescence, to
      promote and facilitate the continued realization of life habits of SLI persons.
      Providing ongoing support throughout the primary years and thereafter is needed
      to facilitate the continuing realization of life habits of SLI persons. Parents
      of children with SLI experience considerable stress in relation to the exercise
      of their parental roles. It is important to intervene and to support parents to
      promote autonomy for their SLI children.

PMID- 26287390
TI  - Responses of the human spleen to exercise.
AB  - The human spleen shows a decrease in volume of around 40% early during vigorous
      exercise and in response to other stressful stimuli such as maximal apnoea and
      the breathing of hypoxic gas mixtures. Contraction seems an active response,
      mediated by alpha-adrenergic fibres in the splenic nerve. Given the relatively
      small size of the human spleen, the effect upon physical performance is likely to
      be small; the augmentation of total blood volume is <2%, and even taking account
      of other causes of haemoconcentration during vigorous exercise, the increase of
      haematocrit is <10%. However, one of two studies suggested that the
      haemoconcentration may be sufficient to cause errors in the traditional method
      for calculating exercise-induced changes of plasma volume. The spleen also
      contributes leucocytes and platelets to the general circulation as part of the
      "fight or flight" reaction to stressors. The mobilisation of leucocytes proceeds
      more slowly than that of the red cells; it depends not only upon an active
      contraction of the spleen, but also a modulation of leucocyte adhesion molecules.
      Splenectomy impairs exercise performance in horses, but human performance data
      are lacking; overall health effects seem minimal, and many patients live many
      years after removal of their spleens. 

PMID- 26287391
TI  - Vascular adhesion protein-1: Role in human pathology and application as a
      biomarker.
AB  - Vascular adhesion protein-1 (VAP-1) is a member of the copper-containing amine
      oxidase/semicarbazide-sensitive amine oxidase (AOC/SSAO) enzyme family. SSAO
      enzymes catalyze oxidative deamination of primary amines, which results in the
      production of the corresponding aldehyde, hydrogen peroxide and ammonium. VAP-1
      is continuously expressed as a transmembrane glycoprotein in the vascular wall
      during development and facilitates the accumulation of inflammatory cells into
      the inflamed environment in concert with other leukocyte adhesion molecules. The
      soluble form of VAP-1 is released into the circulation mainly from vascular
      endothelial cells. Over- and under-expression of sVAP-1 result in alterations of
      the reported reaction product levels, which are involved in the pathogenesis of
      multiple human diseases. The combination of enzymatic and adhesion capacities as
      well as its strong association with inflammatory pathologies makes VAP-1 an
      interesting therapeutic target for drug discovery. In this article, we will
      review the general characteristics and biological functions of VAP-1, focusing on
      its important role as a prognostic biomarker in human pathologies. In addition,
      the potential therapeutic application of VAP-1 inhibitors will be discussed. 

PMID- 26287392
TI  - Single-Incision Total Proctocolectomy and Ileal Pouch Anal Anastomosis in
      Pediatric Patients: Lessons Learned.
AB  - BACKGROUND: Total proctocolectomy (TPC) and ileal pouch anal anastomosis (IPAA)
      have become the standard of care for patients with ulcerative colitis refractory
      to medical management. The purpose of our study is to show our single-site
      approach and to identify maneuvers that improve efficiency. MATERIALS AND
      METHODS: We retrospectively reviewed patients who underwent single-site three
      stage TPC-IPAA for ulcerative colitis at our institution. Primary outcomes
      included operative time, conversion from single site to standard laparoscopy,
      time to oral intake and stoma function, postoperative complications, and length
      of stay. The GelPOINT(TM) Advanced Access Platform (Applied Medical, Santa
      Margarita, CA) was used. RESULTS: Eight patients were identified who had
      undergone single-site surgery with the GelPOINT platform. Six of the 8 patients
      underwent the first stage, total abdominal colectomy (TAC), and all 8 underwent
      the second stage (proctectomy/IPAA). The mean operating time for TAC was 242 +/-
      32 minutes. The mean time until tolerance of clear diet was 1.2 +/- 0.4 days, and
      time until tolerance of regular diet was 3.3 +/- 1.2 days. The mean time to stoma
      function was 1.5 +/- 0.55 days, and that for postoperative opioid use was 4.0 +/-
      1.3 days. The median length of stay was 5 days (range, 3-10 days). There was one
      postoperative complication. The mean operating time for the proctectomy/IPAA was
      283 +/- 50 minutes. The mean time until tolerance of clear diet was 1.0 +/- 0.5
      days, and time until tolerance of regular diet was 3.3 +/- 1.1 days. The mean
      time to stoma function was 1.6 days +/- 0.52 days, and that for postoperative
      opioid use was 3.3 +/- 1.4 days. Median length of stay was 4 days (range, 3-9
      days). There was one postoperative complication. Technical adaptations that
      included extracorporeal mesenteric division, rectal eversion, and rotation of the
      GelPOINT device served to improve the ease and efficiency of the procedure.
      CONCLUSIONS: Single-site TPC-IPAA is both feasible and safe. Incorporation of
      adapted technical maneuvers can increase efficiency.

PMID- 26287393
TI  - In vitro photodynamic therapy based on magnetic-luminescent Gd2O3:Yb,Er
      nanoparticles with bright three-photon up-conversion fluorescence under near
      infrared light.
AB  - Yb(3+) and Er(3+) co-doped Gd2O3 nanoparticles were synthesized via a simple
      homogeneous precipitation method followed by subsequent heat treatment.
      Morphology characterization results showed that these nanoparticles were almost
      spherical in shape with diameters of 200-400 nm. The particles were further
      modified by polyethylene glycol (PEG) to improve their suspensibility in water.
      The sintering temperature was found to greatly influence the fluorescent
      properties of the products. After calcination at 700-1200  degrees C, the
      Gd2O3:Yb,Er nanoparticles could emit bright up-conversion fluorescence under 980
      nm near-infrared (NIR) laser light excitation. The mechanism of up-conversion
      fluorescence was studied in detail and a three-photon process was observed for
      both green and red up-conversion fluorescence of the Gd2O3:Yb,Er nanoparticles.
      Different from many other Yb(3+),Er(3+) co-doped up-conversion materials, the
      prepared Gd2O3:Yb,Er nanoparticles emitted much stronger red light than green
      light. The reason was investigated and ascribed to the presence of abundant
      hydroxyl groups on the surface of the nanoparticles as a result of PEGylation.
      The nanoparticles could be taken up by the human cervical cancer (HeLa) cells and
      presented low toxicity. Well-selected photodynamic therapy (PDT) drugs, methylene
      blue (MB) with a UV/Vis absorption maximum (lambdamax) of 665 nm and 5
      aminolevulinic acid (5ALA) which is a precursor of the natural photosensitizer
      photoporphyrin IX (PpIX) with a lambdamax of 635 nm, were loaded onto the
      nanoparticles respectively to obtain Gd2O3:Yb,Er-MB and Gd2O3:Yb,Er-5ALA
      nanoparticles. Being up-conversion nanoparticles (UCNPs), the taken up
      Gd2O3:Yb,Er nanoparticles exposed to 980 nm laser light emitted red fluorescence
      which activated the loaded MB and PpIX, and then killed the HeLa cells via a PDT
      mechanism. In vitro therapeutic investigation evidenced the prominent PDT effects
      of Gd2O3:Yb,Er-MB and Gd2O3:Yb,Er-5ALA upon NIR light irradiation. In magnetic
      resonance imaging (MRI) studies, the relaxivity values obtained for Gd2O3:Yb,Er
      were r1 = 2.2705 M(-1) s(-1) and r2 = 3.0675 M(-1) s(-1) with a r2/r1 ratio close
      to 1, suggesting that it would be a good candidate as a positive MRI agent. It is
      expected that these particles have applications in magnetic-fluorescent bimodal
      imaging and NIR light-triggered PDT. 

PMID- 26287395
TI  - Well-defined hollow nanochanneled-silica nanospheres prepared with the aid of
      sacrificial copolymer nanospheres and surfactant nanocylinders.
AB  - A new approach for synthesizing well-defined hollow nanochanneled-silica
      nanosphere particles is demonstrated, and the structural details of these
      particles are described for the first time. Positively charged styrene copolymer
      nanospheres with a clean, smooth surface and a very narrow size distribution are
      synthesized by surfactant-free emulsion copolymerization and used as a thermal
      sacrificial core template for the production of core-shell nanoparticles. A
      surfactant/silica composite shell with a uniform thickness is successfully
      produced and deposited onto the polymeric core template by charge density
      matching between the polymer nanosphere template surface and the negatively
      charged silica precursors and then followed by selective thermal decomposition of
      the polymeric core and the surfactant cylinder domains in the shell, producing
      the hollow nanochanneled-silica nanospheres. Comprehensive, quantitative
      structural analyses collectively confirm that the obtained nanoparticles are
      structurally well defined with a hollow core and a shell composed of cylindrical
      nanochannels that provide facile accessibility to the hollow interior space.
      Overall, the hollow nanochanneled-silica nanoparticles have great potential for
      applications in various fields. 

PMID- 26287396
TI  - Modeling Graves' Orbitopathy in Experimental Graves' Disease.
AB  - Graves' orbitopathy (GO), also known as thyroid eye disease is an inflammatory
      disease of the orbital tissue of the eye that arises as a consequence of
      autoimmune thyroid disease. The central feature of the disease is the production
      of antibodies to the thyrotropin hormone receptor (TSHR) that modulate the
      function of the receptor leading to autoimmune hyperthyroidism and GO. Over the
      years, all viable preclinical models of Graves' disease have been incomplete and
      singularly failed to progress in the treatment of orbital complications. A new
      mouse model of GO based upon immunogenic presentation of human TSHR A-subunit
      plasmid by close field electroporation is shown to lead to induction of prolonged
      functional antibodies to TSHR resulting in chronic disease with subsequent
      progression to GO. The stable preclinical GO model exhibited pathologies
      reminiscent of human disease characterized by orbital remodeling by inflammation
      and adipogenesis. Inflammatory lesions characterized by CD3+ T cells and
      macrophages were localized in the orbital muscle tissue. This was accompanied by
      extensive adipogenesis of orbital fat in some immune animals. Surprisingly, other
      signs of orbital involvement were reminiscent of eyelid inflammation involving
      chemosis, with dilated and congested orbital blood vessels. More recently, the
      model is replicated in the author's independent laboratories. The pre-clinical
      model will provide the basis to study the pathogenic and regulatory roles of
      immune T and B cells and their subpopulations to understand the initiation,
      pathophysiology, and progression of GO. 

PMID- 26287397
TI  - Long-term outcomes of a pediatric HIV treatment program in Maputo, Mozambique: a
      cohort study.
AB  - OBJECTIVE: To describe long-term treatment outcomes of a pediatric HIV cohort in
      Mozambique. DESIGN: Retrospective analysis of routine monitoring data. SETTING:
      Secondary health care facilities in the Chamanculo Health District of Maputo.
      SUBJECTS: A total of 1,335 antiretroviral treatment (ART) naive children <15
      years of age enrolled in HIV care between 2002 and 2010. INTERVENTION: HIV care,
      ART (since 2003), task shifting to lower cadre nurses, counseling by lay
      counselors, active patient tracing, nutritional support, support by a
      psychologist, targeted viral load testing, and switch to second-line treatment.
      MAIN OUTCOME MEASURES: Kaplan-Meier estimates for retention in care (RIC), CD4
      cell percentage, body mass index for age z-score, and adjusted incidence rate
      ratios for attrition (death or loss to follow-up) as calculated by Poisson
      regression. RESULTS: The RIC at 6 years in the pre-ART cohort was 44% (95%
      confidence interval: 38-49), and the one at 8 years in the ART cohort was 70% (64
      75). Risk factors for attrition included young age, low CD4 percentage,
      underweight, active tuberculosis, and enrollment/treatment initiation after 2006.
      The mean CD4 percentage increased strongly at 1 year on treatment and remained
      high thereafter. The body mass index for age z-score sharply increased at 1 year
      after treatment initiation before stabilizing at pre-ART levels thereafter.
      CONCLUSIONS: Good clinical and immunological treatment outcomes up to 8 years of
      follow-up on ART can be achieved in a context of shortage of health workers and a
      high level of task-shifting approach.

PMID- 26287398
TI  - Effects of metoclopramide-induced hyperprolactinemia on the prolactin and
      prolactin receptor expression of murine adrenal.
AB  - The aim of this study was to evaluate the effects of metoclopramide-induced
      hyperprolactinemia on the prolactin (PRL) and prolactin receptor's (PRLR)
      expression in the adrenal. For this purpose, a total of 12 animals with intact
      ovaries were allocated to two groups: G1 (saline solution) and G2
      (metoclopramide). A total of 30 oophorectomized animals was randomized to five
      subgroups: G3 (saline solution), G4 (metoclopramide), G5 (metoclopramide + 17beta
      estradiol), G6 (metoclopramide + progesterone), and G7 (metoclopramide + 17beta
      estradiol + progesterone). Immunohistochemical analyses were evaluated semi
      quantitatively. For PRLR, the area fraction of labeled cells (ALC) varied from 1
      (0-10%) to 3 (> 50%). Based on the mean of the immunostaining intensity, G2 and
      G4 showed strong expression; G6 and G7 presented a mild reaction; and G1, G3, and
      G5 exhibited a weak reaction. Concerning PRL, the ALC varied from 1 (0-10%) to 3
      (> 50%), and groups G6 and G7 showed a strong reaction; G2, G4, and G5 showed a
      mild reaction; and G1 and G3 exhibited a weak reaction. These findings suggest
      that metoclopramide-induced hyperprolactinemia increases PRL expression in the
      adrenal glands of mice. Furthermore, progesterone alone or in association with
      estrogen also increases PRL expression, but to a lesser extent.

PMID- 26287400
TI  - Notice of Redundant Publication.

PMID- 26287399
TI  - NHC-catalyzed activation of alpha,beta-unsaturated N-acyltriazoles: an easy
      access to dihydropyranones.
AB  - An N-heterocyclic carbene catalyzed activation of alpha,beta-unsaturated N
      acyltriazoles is described. The in situ generated alpha,beta-unsaturated
      acylazolium intermediates allowed an enantioselective formal [3+3] cycloaddition
      with 1,3-dicarbonyl compounds. The resulting dihydropyranones are formed in good
      to excellent yields and with high enantioselectivities. 

PMID- 26287401
TI  - Lanostane Triterpenes from the Tibetan Medicinal Mushroom Ganoderma
      leucocontextum and Their Inhibitory Effects on HMG-CoA Reductase and alpha
      Glucosidase.
AB  - Sixteen new lanostane triterpenes, ganoleucoins A-P (1-16), together with 10
      known tripterpenes (17-26), were isolated from the cultivated fruiting bodies of
      Ganoderma leucocontextum, a new member of the Ganoderma lucidum complex. The
      structures of the new compounds were elucidated by extensive spectroscopic
      analysis and chemical transformation. The inhibitory effects of 1-26 on HMG-CoA
      reductase and alpha-glucosidase were tested in vitro. Compounds 1, 3, 6, 10-14,
      17, 18, 23, 25, and 26 showed much stronger inhibitory activity against HMG-CoA
      reductase than the positive control atorvastatin. Compounds 13, 14, and 16
      presented potent inhibitory activity against alpha-glucosidase from yeast with
      IC50 values of 13.6, 2.5, and 5.9 MUM, respectively. In addition, the
      cytotoxicity of 1-26 was evaluated against the K562 and PC-3 cell lines by the
      MTT assay. Compounds 1, 2, 6, 7, 10, 12, 16, 18, and 25 exhibited cytotoxicity
      against K562 cells with IC50 values in the range 10-20 MUM. Paclitaxel was used
      as the positive control with an IC50 value of 0.9 MUM. This is the first report
      of secondary metabolites from this medicinal mushroom.

PMID- 26287402
TI  - MicroRNA-1285 Regulates 17beta-Estradiol-Inhibited Immature Boar Sertoli Cell
      Proliferation via Adenosine Monophosphate-Activated Protein Kinase Activation.
AB  - This study investigated the capacity of 10 MUM 17beta-estradiol to inhibit
      immature boar Sertoli cell (SC) proliferation and the involvement of microRNA
      (miR)-1285 in this process. SC viability and cell cycle progression were
      investigated using a cell counting kit-8 and flow cytometry, respectively.
      Expression of AMP-activated protein kinase (AMPK), S phase kinase-associated
      protein 2 (Skp2), and miR-1285 was analyzed by real-time RT-PCR and Western
      blotting. 17beta-Estradiol (10 MUM) reduced SC viability and miR-1285 expression
      and promoted AMPK phosphorylation. A double-stranded synthetic miR-1285 mimic
      promoted SC viability, increased levels of ATP, and phosphorylated mammalian
      target of rapamycin (mTOR) and Skp2 mRNA and protein, whereas p53 and p27
      expression decreased, and 17beta-estradiol-mediated effects on SCs were
      significantly attenuated. A single-stranded synthetic miR-1285 inhibitor produced
      the opposite effects on these measures. Activation of AMPK inhibited SC
      viability, reduced levels of ATP, phosphorylated mTOR and Skp2 mRNA and protein,
      and increased p53 and p27 expression. An AMPK inhibitor (compound C) attenuated
      the effects of 17beta-estradiol on SCs. This indicated that 17beta-estradiol (10
      MUM) reduced SC proliferation by inhibiting miR-1285 and thus activating AMPK.
      Phosphorylated AMPK is involved in the regulation of 17beta-estradiol-mediated
      inhibition of SC viability through increasing p53 and p27 expression and
      inhibiting mTOR and Skp2 expression. Our findings also implicated Skp2 as the
      downstream integration point of p53 and mTOR. These findings indicated that miR
      1285 may represent a target for the manipulation of boar sperm production. 

PMID- 26287403
TI  - Thyroid Hormone at Near Physiologic Concentrations Acutely Increases Oxygen
      Consumption and Extracellular Acidification in LH86 Hepatoma Cells.
AB  - Thyroid hormone (T3) has been known to regulate the basal metabolic rate for more
      than a century, but mechanistic understanding is lacking both at the level of the
      intact organism and in terms of how T3 alters energy expenditure in individual
      tissues. The current studies investigate the question of which metabolically
      relevant genes respond acutely as T3 concentrations increase through the
      physiologic range in liver cells. Because this has been technically unfeasible
      historically, we developed a modified protocol for extracellular flux analysis
      using a 96-well Extracellular Flux Analyzer (Seahorse Bioscience). Using a
      modified extracellular flux protocol and LH86 human hepatoma cells, we
      established an experimental system where small but significant changes in O2
      consumption could be reproducibly quantified as hypothyroid cells were exposed to
      near-physiologic final concentrations of T3 approximately 2 orders of magnitude
      lower than most studies (0.04 nM free T3), in only 6-7 hours. Taking advantage of
      the nondestructive nature of 96-well Extracellular Flux Analyzer measurements,
      the acute, direct, transcriptional changes that occur were measured in the exact
      same cells demonstrating increased O2 consumption. An unbiased, genome-wide
      microarray analysis identified potential candidate genes related to fatty acid
      oxidation, angiogenesis, nucleotide metabolism, immune signaling, mitochondrial
      respiration, and cell proliferation. The identified transcriptome is likely
      enriched in the genes most important for mediating the energetic effects of T3 in
      hepatoma cells.

PMID- 26287404
TI  - Pentraxin-3 Is a TSH-Inducible Protein in Human Fibrocytes and Orbital
      Fibroblasts.
AB  - CD34(+) fibrocytes are bone marrow-derived monocyte progenitor cells that traffic
      to sites of tissue injury and repair. They putatively infiltrate the orbit in
      thyroid-associated ophthalmopathy where they appear to transition into CD34(+)
      orbital fibroblasts (OFs) that interact with residential CD34(-) fibroblasts. A
      unique phenotypic attribute of fibrocytes and CD34(+) OFs is their expression of
      the functional thyrotropin receptor (TSHR) and other "thyroid-specific" proteins.
      When activated through TSHR, fibrocytes express a number of cytokines and other
      inflammatory genes. Here we sought to determine whether pentraxin-3 (PTX-3), an
      acute-phase protein involved in inflammation and autoimmunity, might be induced
      by TSH in fibrocytes and OFs. These cells were collected from patients with
      Graves disease and healthy individuals. PTX-3 mRNA levels were determined by real
      time PCR, protein was determined by ELISA and Western blot, and PTX-3 gene
      promoter activity was assessed with reporter assays. PTX-3 expression was induced
      by TSH in both cell types, regardless of the health status of the donor and was a
      consequence of increased steady-state PTX-3 mRNA levels. M22, a TSHR-activating
      monoclonal antibody, also induced PTX-3. The induction could be attenuated by
      dexamethasone and by IGF-I receptor-blocking antibodies, teprotumumab and 1H7.
      TSH effects were mediated through phosphatidylinositol 3-kinase/AKT, mammalian
      target of rapamycin/p70(s6k), Janus tyrosine kinase 2 pathways, and enhanced PTX
      3 mRNA stability. These findings indicate that PTX-3 is a TSH target gene, the
      expression of which can be induced in fibrocytes and OFs. They suggest that PTX-3
      might represent a previously unidentified nexus between the thyroid axis and the
      mechanisms involved in tissue remodeling. 

PMID- 26287405
TI  - Bone Marrow MicroRNA-335 Level Predicts the Chemotherapy Response and Prognosis
      of Adult Acute Myeloid Leukemia.
AB  - The aim of this study was to investigate the role of microRNA-335 (miR-335) in
      determining the treatment response and prognosis in adult acute myeloid leukemia
      (AML) patients receiving the cytarabine (Ara-C)-based chemotherapy.A total of 204
      adult AML patients were collected. The miR-335 levels in serum and bone marrow
      samples from these patients were determined. All patients received Ara-C-based
      standard induction chemotherapy regimens. The treatment response to Ara-C-based
      chemotherapy was evaluated. All patients were followed for prognostic
      analyses.The levels of miR-335 in bone marrow and serum samples from adult AML
      patients achieving complete response were significantly higher than those
      without. The serum miR-335 level was not associated with the chemotherapy
      response and prognosis in these AML patients. In contrast, high bone marrow miR
      335 level was significantly associated with a poor treatment response and also
      predicted a worse prognosis indicated by the relapse-free survival and overall
      survival periods in adult AML patients receiving Ara-C-based chemotherapy.Our
      finding suggests that bone marrow miR-335 level may be used as a marker to
      predict the chemotherapy response and prognosis in adult AML patients. 

PMID- 26287406
TI  - A Population-Based Study of 30-day Incidence of Ischemic Stroke Following
      Surgical Neck Dissection.
AB  - The objective of this study was to determine the 30-day incidence of ischemic
      stroke following neck dissection compared to matched patients undergoing non-head
      and neck surgeries.A surgical dissection of the neck is a common procedure
      performed for many types of cancer. Whether such dissections increase the risk of
      ischemic stroke is uncertain.A retrospective cohort study using data from linked
      administrative and registry databases (1995-2012) in the province of Ontario,
      Canada was performed. Patients were matched 1-to-1 on age, sex, date of surgery,
      and comorbidities to patients undergoing non-head and neck surgeries. The primary
      outcome was ischemic stroke assessed in hospitalized patients using validated
      database codes.A total of 14,837 patients underwent surgical neck dissection. The
      30-day incidence of ischemic stroke following the dissection was 0.7%. This
      incidence decreased in recent years (1.1% in 1995 to 2000; 0.8% in 2001 to 2006;
      0.3% in 2007 to 2012; P for trend <0.0001). The 30-day incidence of ischemic
      stroke in patients undergoing neck dissection is similar to matched patients
      undergoing thoracic surgery (0.5%, P = 0.26) and colectomy (0.5%, P = 0.1).
      Factors independently associated with a higher risk of stroke in 30 days
      following neck dissection surgery were of age >=75 years (odds ratio (OR) 1.63,
      95% confidence interval (CI) 1.05-2.53), and a history of diabetes (OR 1.60, 95%
      CI 1.02-2.49), hypertension (OR 2.64, 95% CI 1.64-4.25), or prior stroke (OR
      4.06, 95% CI 2.29-7.18).Less than 1% of patients undergoing surgical neck
      dissection will experience an ischemic stroke in the following 30 days. This
      incidence of stroke is similar to thoracic surgery and colectomy.

PMID- 26287407
TI  - Role of Trimetazidine in Ischemic Preconditioning in Patients With Symptomatic
      Coronary Artery Disease.
AB  - Ischemic preconditioning (IP) is a powerful cardioprotective cellular mechanism
      that has been related to the "warm-up phenomenon" or "walk-through" angina, and
      has been documented through the use of sequential exercise tests (ETs). It is
      known that several drugs, for example, cromokalim, pinacidil, adenosine, and
      nicorandil, can interfere with the cellular pathways of IP. The purpose of this
      article is to report the effect of the anti-ischemic agent trimetazidine (TMZ) on
      IP in symptomatic coronary artery disease (CAD) patients.We conducted a
      prospective study evaluating IP by the analysis of ischemic parameters in 2
      sequential ETs. In phase I, without TMZ, patients underwent ET1 and ET2 with a 30
      minute interval between them. In phase II, after 1 week of TMZ 35 mg twice daily,
      all patients underwent 2 consecutive ETs (ET3 and ET4). IP was considered present
      when the time to 1.0-mm segment ST on electrocardiogram deviation (T-1.0 mm) and
      rate pressure product (RPP) were greater in the second of 2 tests. The
      improvement in T-1.0 mm and RPP were compared in the 2 phases: without TMZ and
      after 1-week TMZ to assess the action of such drug in myocardial protective
      mechanisms. ETs were analyzed by 2 independent cardiologists.From 135 CAD
      patients screened, 96 met inclusion criteria and 62 completed the study protocol.
      Forty patients manifested IP by demonstrating an improvement in T-1.0 mm in ET2
      compared with ET1, without the use of any drugs (phase I). In phase II, after 1
      week TMZ, 26 patients (65%) did not show any incremental result in ischemic
      parameters in ET4 compared with ET3. Furthermore, of these patients, 8 (20%) had
      IP blockage.In this study, TMZ did not add any benefit to IP in patients with
      stable symptomatic CAD. 

PMID- 26287408
TI  - Association Between Diabetic Macular Edema and Cardiovascular Events in Type 2
      Diabetes Patients: A Multicenter Observational Study.
AB  - Diabetic macular edema (DME) is the main cause of visual loss associated with
      diabetes but any association between DME and cardiovascular events is
      unclear.This study aims to describe the possible association between DME and
      cardiovascular events in a multicenter cross-sectional study of patients with
      type 2 diabetes.Two thousand eight hundred seven patients with type 2 diabetes
      were recruited from diabetes and nephrology clinical institutional centers
      participating in the DIAB 2 NEPHROGENE study focusing on diabetic complications.
      DME (presence/absence) and diabetic retinopathy (DR) classification were based on
      ophthalmological report and/or on 30 degrees  color retinal photographs. DR was
      defined as absent, nonproliferative (background, moderate, or severe) or
      proliferative. Cardiovascular events were stroke, myocardial infarction, and
      lower limb amputation.Details regarding associations between DME and
      cardiovascular events were evaluated.The study included 2807 patients with type 2
      diabetes, of whom 355 (12.6%) had DME. DME was significantly and independently
      associated with patient age, known duration of diabetes, HbA1c, systolic blood
      pressure, and DR stage. Only the prior history of lower limb amputation was
      strongly associated with DME in univariate and multivariate analyses, whereas no
      association was found with regard to myocardial infarction or stroke. Moreover,
      both major (n = 32) and minor lower limb (n = 96) amputations were similarly
      associated with DME, with respective odds ratio of 3.7 (95% confidence interval
      [CI], 1.77-7.74; P = 0.0012) and of 4.29 (95% CI, 2.79-6.61; P < 0.001).DME is
      strongly and independently associated with lower limb amputation in type 2
      diabetic patients. 

PMID- 26287409
TI  - Differences of Retinal Blood Flow Between Arteries and Veins Determined by Laser
      Speckle Flowgraphy in Healthy Subjects.
AB  - To characterize the total retinal blood flow determined by laser speckle
      flowgraphy (LSFG) of healthy subjects.This prospective cross-sectional study was
      conducted at the Nagoya University Hospital. One hundred fifteen right eyes of
      115 healthy subjects (mean age: 39.4 +/- 16.1 years) were studied. The total
      blood flow in the retinal arteries and veins around the optic nerve head was
      measured separately using the total retinal flow index (TRFI), which represents
      blood flow volume. The lumen diameters of the retinal vessels determined by LSFG
      and by adaptive optics (AO) camera were compared. The images obtained by LSFG and
      AO camera were merged, and the distribution of the mean blur rates (MBRs), which
      represent the velocities of the erythrocytes, was evaluated on the images.The
      mean TRFI in veins (1812 +/- 445, arbitral units) was significantly higher than
      that in arteries (1455 +/- 348, arbitral units; P < 0.001). Linear regression
      analysis showed a significant correlation between the TRFI in the arteries and
      veins (P < 0.001). Linear regression analysis also showed a highly significant
      correlation between the diameters of arteries and veins determined by LSFG and by
      the AO camera (arteries, r = 0.94, P < 0.001; veins, r = 0.92, P < 0.001). The
      ratios of the lumen diameters determined by LSFG to that by AO camera was
      significant lower in arteries (0.068 +/- 0.005, arbitral units) than in veins
      (0.074 +/- 0.007, arbitral units) (P < 0.001). The MBRs of veins were homogeneous
      throughout the width of the lumen; however, the MBRs in the arteries were higher
      at the center and lower close to the walls of the lumen.The higher TRFIs in the
      veins than in the arteries indicate that there is a smaller volume of retinal
      blood flow in arteries than veins. However, the possibility remains that LSFG has
      inherent problem that the arterial lumen diameter determined by LSFG is smaller
      than actual one because of the characteristics of arteries. This would result in
      a smaller volume of retinal blood flow in the arteries than veins in LSFG.

PMID- 26287410
TI  - Do Recent Advances in Diagnostic and Therapeutic Procedures Negate the Benefit of
      Postmastectomy Radiotherapy in N1 Patients With a Low Risk of Locoregional
      Recurrence?
AB  - Recent advances in breast cancer management might make the use of postmastectomy
      radiotherapy (PMRT) redundant in the treatment of pT1/T2N1 patients. We
      investigated the impact of PMRT on disease-free survival (DFS) in these patients
      who have a low risk of locoregional recurrence (LRR) after contemporary
      multidisciplinary management.Between 1998 and 2011, 1123 patients underwent
      upfront surgery for pathologically diagnosed pT1/T2N1 breast cancer, at a single
      institution. A retrospective review was performed on 692 patients who had a
      mastectomy with axillary lymph node (LN) clearance. Most patients received
      adjuvant systemic chemotherapy and/or endocrine therapy. PMRT was administered to
      17.8% of the patients. The median follow-up time was 98 months.The entire cohort
      was divided into 2 groups, the early-era (1998-2003) and late-era (2004-2011)
      cohorts. Grouping was based on the use of modern therapies since 2004 including
      sentinel LN (SLN) biopsy, anthracycline/taxane-based chemotherapy, and aromatase
      inhibitors. Late-era patients had a significantly lower 5-year LRR compared with
      early-era patients (3.2% vs 10.3%, respectively; P < 0.001). In late-era
      patients, although PMRT did not significantly reduce the 5-year LRR rate (1% vs
      3.8%, respectively), it did improve the 5-year DFS rate (96.1% vs 87.5%,
      respectively). After controlling for all clinicopathological variables, PMRT was
      independently associated with improved DFS. In subgroup analysis, depending on
      the presence of micro- or macrometastasis in the axillary nodes, the benefit of
      PMRT was most apparent in patients with macrometastasis (hazard ratio, 0.19). In
      the late-era cohort with no PMRT, the 3-year distant metastasis risk increased
      according to LN tumor burden (0%, 5.2%, and 9.8% in micrometastasis, SLN
      macrometastasis, and non-SLN macrometastasis, respectively).Advanced surgical and
      systemic therapies might not negate the benefit of PMRT in recently diagnosed pN1
      patients who have a very low risk for LRR. Our data indicate that the overall
      recurrence risk combined with the LRR should be considered for an indication of
      PMRT, and raises the question of whether the receipt of PMRT would improve
      outcome in patients with micrometastasis. 

PMID- 26287413
TI  - Comparisons Between Different Procedures of No. 10 Lymphadenectomy for Gastric
      Cancer Patients With Total Gastrectomy.
AB  - To compare the effectiveness and safety of in-vivo dissection procedure of No. 10
      lymph nodes with those of ex-vivo dissection procedure for gastric cancer
      patients with total gastrectomy.Patients were divided into in-vivo group and ex
      vivo group according to whether the dissection of No. 10 lymph nodes were
      performed after the mobilization of the pancreas and spleen, and migration out
      from peritoneal cavity. Clinicopathologic characteristics, overall survival,
      morbidity, and mortality were compared between the 2 groups.There were 148
      patients in in-vivo group, while 30 in ex-vivo group. The baselines between the 2
      groups were almost comparable. The metastatic ratio of No. 10 lymph nodes were
      6.1% and 10.0% (P = 0.435) and the metastatic degree were 7.9% and 13.6% (P =
      0.158) for in-vivo group and ex-vivo group, respectively. There was no difference
      in morbidity or mortality between the 2 groups. The number of total harvested
      lymph nodes and No. 10 lymph nodes increased significantly in ex-vivo group at
      the cost of prolonged operation time. The estimated overall survival rates for
      patients in in-vivo group and ex-vivo group were (3-year: 52.0% vs 61.8%) and (5
      year: 45.3% vs 49.5%), respectively, without statistical significance. Further
      multivariable analysis had showed that the procedure of No. 10 lymphadenectomy
      was not a significant independent prognostic factor.Both in-vivo and ex-vivo
      dissection of No. 10 lymph nodes could be performed safely. It seems that ex-vivo
      dissection of No. 10 lymph nodes can result in a higher effective dissection at
      the cost of the operation time, but the overall survival rates were not
      statistically significant between the 2 groups, which should be confirmed further
      in a well-designed randomized controlled trial. 

PMID- 26287411
TI  - Lycopene and Risk of Prostate Cancer: A Systematic Review and Meta-Analysis.
AB  - Prostate cancer (PCa) is a common illness for aging males. Lycopene has been
      identified as an antioxidant agent with potential anticancer properties. Studies
      investigating the relation between lycopene and PCa risk have produced
      inconsistent results. This study aims to determine dietary lycopene
      consumption/circulating concentration and any potential dose-response
      associations with the risk of PCa. Eligible studies published in English up to
      April 10, 2014, were searched and identified from Pubmed, Sciencedirect Online,
      Wiley online library databases and hand searching. The STATA (version 12.0) was
      applied to process the dose-response meta-analysis. Random effects models were
      used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs)
      and to incorporate variation between studies. The linear and nonlinear dose
      response relations were evaluated with data from categories of lycopene
      consumption/circulating concentrations. Twenty-six studies were included with
      17,517 cases of PCa reported from 563,299 participants. Although inverse
      association between lycopene consumption and PCa risk was not found in all
      studies, there was a trend that with higher lycopene intake, there was reduced
      incidence of PCa (P = 0.078). Removal of one Chinese study in sensitivity
      analysis, or recalculation using data from only high-quality studies for subgroup
      analysis, indicated that higher lycopene consumption significantly lowered PCa
      risk. Furthermore, our dose-response meta-analysis demonstrated that higher
      lycopene consumption was linearly associated with a reduced risk of PCa with a
      threshold between 9 and 21 mg/day. Consistently, higher circulating lycopene
      levels significantly reduced the risk of PCa. Interestingly, the concentration of
      circulating lycopene between 2.17 and 85 MUg/dL was linearly inversed with PCa
      risk whereas there was no linear association >85 MUg/dL. In addition, greater
      efficacy for the circulating lycopene concentration on preventing PCa was found
      for studies with high quality, follow-up >10 years and where results were
      adjusted by the age or the body mass index. In conclusion, our novel data
      demonstrates that higher lycopene consumption/circulating concentration is
      associated with a lower risk of PCa. However, further studies are required to
      determine the mechanism by which lycopene reduces the risk of PCa and if there
      are other factors in tomato products that might potentially decrease PCa risk and
      progression. 

PMID- 26287412
TI  - BIM Gene Polymorphism Lowers the Efficacy of EGFR-TKIs in Advanced Nonsmall Cell
      Lung Cancer With Sensitive EGFR Mutations: A Systematic Review and Meta-Analysis.
AB  - The strong association between bcl-2-like 11 (BIM) triggered apoptosis and the
      presence of epidermal growth factor receptor (EGFR) mutations has been proven in
      nonsmall cell lung cancer (NSCLC). However, the relationship between EGFR
      tyrosine kinase inhibitor's (TKI's) efficacy and BIM polymorphism in NSCLC EGFR
      is still unclear.Electronic databases were searched for eligible literatures.
      Data on objective response rates (ORRs), disease control rates (DCRs), and
      progression-free survival (PFS) stratified by BIM polymorphism status were
      extracted and synthesized based on random-effect model. Subgroup and sensitivity
      analyses were conducted.A total of 6 studies that involved a total of 773 EGFR
      mutant advanced NSCLC patients after EGFR-TKI treatment were included. In
      overall, non-BIM polymorphism patients were associated with significant prolonged
      PFS (hazard ratio 0.63, 0.47-0.83, P = 0.001) compared to patients with BIM
      polymorphism. However, only marginal improvements without statistical
      significance in ORR (odds ratio [OR] 1.71, 0.91-3.24, P = 0.097) and DCR (OR
      1.56, 0.85-2.89, P = 0.153) were observed. Subgroup analyses showed that the
      benefits of PFS in non-BIM polymorphism group were predominantly presented in
      pooled results of studies involving chemotherapy-naive and the others, and
      retrospective studies. Additionally, we failed to observe any significant benefit
      from patients without BIM polymorphism in every subgroup for ORR and DCR.For
      advanced NSCLC EGFR mutant patients, non-BIM polymorphism ones are associated
      with longer PFS than those with BIM polymorphism after EGFR-TKIs treatment. BIM
      polymorphism status should be considered an essential factor in studies regarding
      EGFR-targeted agents toward EGFR mutant patients. 

PMID- 26287414
TI  - A Rare Case of Breast Malignant Phyllodes Tumor With Metastases to the Kidney:
      Case Report.
AB  - Phyllodes tumors are rare breast neoplasms. Surgery is the treatment of choice.
      The role of postoperative radiotherapy and chemotherapy is still under dispute,
      as there are no equivocal prognostic factors. Treatment failure results in the
      occurrence of distant metastasis-mainly to the lungs, bones, liver, and brain. We
      have described the case of a woman with a malignant phyllodes tumor of the breast
      that was surgically treated. She did not receive adjuvant therapy because there
      is no consensus on the role of postoperative chemotherapy and radiotherapy. One
      year following the surgery, the patient had left-sided nephrectomy performed
      because of a rapidly growing tumor of the kidney. Renal cancer was suspected;
      however, a histopathological examination revealed that it was a metastatic
      phyllodes tumor. At the same time, the patient was diagnosed as having metastases
      in the other kidney, the lungs, liver, and bones.Our case report describes not
      only an unusual localization of the metastases (in the kidneys), but also failure
      of the chemotherapy and the aggressive course of malignant phyllodes tumor.
      Identification of patients with high risk for distant metastasis and the
      introduction of uniform rules for the management of adjuvant chemotherapy and
      radiotherapy would make planning treatment as efficacious as possible. 

PMID- 26287415
TI  - Loss of MiR-664 Expression Enhances Cutaneous Malignant Melanoma Proliferation by
      Upregulating PLP2.
AB  - Proteolipid protein 2 (PLP2) has been shown to be upregulated in several cancers,
      including breast cancer, hepatocellular carcinoma, osteosarcoma, and melanoma.
      PLP2 specifically binds to phosphatidylinositol 3 kinase to activate the protein
      kinase B pathway to enhance cell proliferation, adhesion, and invasion in
      melanoma cells. Therefore, we speculated that PLP2 exhibits oncogenic potential.
      However, the regulatory mechanisms of PLP2 in cancer cells remain unclear.Herein,
      we found that microRNA (miR)-664 expression was significantly downregulated in
      cutaneous malignant melanoma (CMM) cells and tissues compared with normal human
      melanocytes and benign melanocytic naevi. MiR-664 expression level was
      significantly correlated with patient survival. Ectopic expression of miR-664
      reduced CMM cell proliferation and anchorage-independent growth, whereas the
      inhibition of miR-664 induced these effects. Furthermore, inhibition of miR-664
      in CMM cells resulted in modulation of their entry into the G1/S transitional
      phase, which was caused by downregulation of the cyclin-dependent kinase
      inhibitor P21 and upregulation of the cell-cycle regulator cyclin D1. Moreover,
      we demonstrated that miR-664 downregulated PLP2 expression by directly targeting
      the PLP2 untranslated region.Taken together, our results suggest that miR-664 may
      play an important role in suppressing proliferation of CMM cells and present a
      novel mechanism of miR-mediated direct suppression of PLP2 expression in cancer
      cells. 

PMID- 26287416
TI  - Hepatitis C Virus Infection Is Associated With an Increased Risk of Active
      Tuberculosis Disease: A Nationwide Population-Based Study.
AB  - Tuberculosis (TB) and hepatitis C virus (HCV) infection contribute to major
      disease mortality and morbidity worldwide. However, the causal link between HCV
      infection and TB risk remains unclear. We conducted a population-based cohort
      study to elucidate the association between HCV infection and TB disease by
      analyzing Taiwan National Health Insurance Database. We enrolled 5454 persons
      with HCV infection and 54,274 age- and sex-matched non-HCV-infected persons
      between January 1998 and December 2007. Time-dependent Cox proportional hazards
      regression analysis was used to measure the association between HCV infection and
      active TB disease. Incidence rate of active TB disease was higher among HCV
      infection than in control (134.1 vs 89.1 per 100,000 person-years; incidence rate
      ratio 1.51; P = 0.014). HCV infection was significantly associated with active TB
      disease in multivariate Cox regression (adjusted hazard ratio [HR] 3.20; 95%
      confidence interval [CI], 1.85-5.53; P < 0.001) and competing death risk event
      analysis (adjusted HR 2.11; 95% CI, 1.39-3.20; P < 0.001). Multivariate
      stratified analysis further revealed that HCV infection was a risk of active TB
      disease in most strata. This nationwide cohort study suggests that HCV infection
      is associated with a higher risk of developing active TB disease. 

PMID- 26287417
TI  - Assessment of Blood Glucose Regulation and Safety of Resistant Starch Formula
      Based Diet in Healthy Normal and Subjects With Type 2 Diabetes.
AB  - To evaluate the effects of the new resistant starch (RS) formula, PPB-R-203, on
      glucose homeostasis in healthy subjects and subjects with type 2 diabetes.A
      cohort consisting of 40 healthy participants received test and control diets and
      was checked for up to 3 hours post-meal. A randomized, 2-regimen, cross-over,
      comparative study was conducted in 44 subjects with type 2 diabetes and glycemic
      control was assessed with a continuous glucose monitoring system.In healthy
      participants, serum glucose values and incremental areas under the glucose curves
      (AUC) were significantly lower in the PPB-R-203 than the control group (P <
      0.05). In patients with type 2 diabetes, mean blood glucose concentrations for
      subjects on the control regimen were higher than those for subjects on the PPB-R
      203-based regimen (7.9 +/- 1.7, 95% confidence interval [CI] 7.4-8.4 vs 7.4 +/-
      1.6, 95% CI 6.9-7.9 mmol/L, respectively; P = 0.023). AUCs for total blood
      glucose and hyperglycemia (glucose >10 mmol/L) were also reduced for subjects on
      the PPB-R-203-based regimen as compared with those on control regimen (total
      blood glucose: 16.2 +/- 4.0, 95% CI 14.9-17.4 vs 18.7 +/- 4.0, 95% CI 17.6-20.1,
      P < 0.001; hyperglycemia: 4.9 +/- 5.7, 95% CI 3.1-6.6 vs 6.3 +/- 6.4, 95% CI 4.3
      8.3 mmol/L * day, P = 0.021). However, AUC measurements for hypoglycemia (glucose
      <3.9 mmol/l) were not statistically significant.A PPB-R-203-based diet reduced
      postprandial hyperglycemia in patients with type 2 diabetes without increasing
      the risk of hypoglycemia or glucose excursion. 

PMID- 26287418
TI  - Effect of mu Agonists on Long-Term Survival and Recurrence in Nonsmall Cell Lung
      Cancer Patients.
AB  - Opioids are widely used for postoperative analgesia. Morphine may have an effect
      on cell replication, migration, and cancer recurrence. However, the association
      of postoperative mu agonists with outcome of nonsmall cell lung cancer (NSCLC)
      patients has not been fully investigated.We retrospectively evaluated the impact
      of postoperative mu agonists on overall survival (OS) and disease-free survival
      (DFS) in early stage NSCLC patients. Patients and relevant medical information
      were selected from the Bio-Bank of Shandong Provincial Hospital. Difference of
      clinicopathologic information in postoperative mu agonists group and no mu
      agonists group was analyzed by chi test. Univariate and multivariate Cox
      regression analysis were conducted and represented as hazards ratio and 95%
      confidence interval form. The primary endpoint was OS and secondary endpoint was
      DFS.This retrospective study included 984 consecutive NSCLC patients who
      underwent surgery between January 2006 and December 2011. No significant
      difference existed between postoperative mu agonists usage group and no mu
      agonists usage group in clinicopathologic information except operation type (P =
      0.041). Postoperative mu agonists usage was related to shorter OS (HR 1.514, 95%
      CI 1.197-1.916, P = 0.001) and shorter DFS (HR 1.415, 95% CI 1.123-1.781, P =
      0.003) in the multivariate Cox regression model. For the patients who received
      postoperative chemotherapy or radiotherapy postoperative mu agonists also predict
      shorter survival (HR 1.437, 95% CI 1.041-1.982, P = 0.027). Subgroup analysis
      showed that administration of postoperative mu agonists was related to shorter
      OS, especially in males, more smoking, poor differential degree, bilobectomy or
      pneumonectomy, and stage III subgroup, respectively.Administration of
      postoperative mu agonists was related to shorter OS and DFS for the NSCLC
      patients who underwent surgery. 

PMID- 26287419
TI  - Association Between History of Severe Hypoglycemia and Risk of Falls in Younger
      and Older Patients With Diabetes.
AB  - To compare the incidence and relative risk of falls between adults with and
      without diabetes, and to prospectively assess the role of history of severe
      hypoglycemia in the putative relationship between diabetes and falls in younger
      and older people, respectively.The National Health Insurance Research Database in
      Taiwan was used in this cohort study. Diabetic cases (with and without history of
      severe hypoglycemia) and nondiabetic people were followed from 2000 to 2009.
      There were 31,049 people enrolled in each of the 3 groups. Subdistribution hazard
      ratio (sHR) of falls was estimated with considering death as a competing risk by
      using Fine and Gray method. Demographic characteristics, diabetes-related
      complications, and comorbidities associated with falls were adjusted in
      multivariable Cox regression model.As compared to nondiabetic people, adjusted
      sHR was 1.13 for diabetes without history of severe hypoglycemia (DwoH) and 1.63
      for diabetes with history of severe hypoglycemia (DwH), respectively. DwH group
      was associated with a higher risk than DwoH (adjusted sHR = 1.57). All of the
      excessive risks were more pronounced in people younger than 65 years old than in
      older people.Patients with diabetes had increased risk of falls. Severe
      hypoglycemia was further associated with a higher risk in diabetes, the increased
      hazards were particularly pronounced in people younger than 65 years old. Because
      falls in younger people may result in a greater economic and social loss, our
      study call for proper attentions to prevention of falls in younger patients (<65
      years old) with diabetes. 

PMID- 26287420
TI  - Adiponectin as a Protective Factor Against the Progression Toward Type 2 Diabetes
      Mellitus in Postmenopausal Women.
AB  - Serum adiponectin levels have been suggested to be predictors of type 2 diabetes
      mellitus in diverse populations. However, the relationship between circulating
      adiponectin levels and the risk of development of type 2 diabetes in
      postmenopausal women has not been investigated.A total of 382 healthy
      postmenopausal women who participated in a prospective cohort study were followed
      for 5.8 years. Type 2 diabetes mellitus was defined according to the criteria set
      out by the American Diabetes Association. Adiponectin, osteoprotegerin (OPG), and
      high-sensitivity C-reactive protein (hs-CRP) levels were measured using ELISA.Of
      195 women who did not have diabetes at baseline and who were reexamined in the
      second phase of the study for diabetic status, 35 subjects (17.9%) developed type
      2 diabetes mellitus during the 5.8 years follow-up period. The women with type 2
      diabetes had lower adiponectin levels than the healthy postmenopausal women.
      Multiple regression analysis showed that, after adjustments were made for age,
      cardiovascular risk factors, OPG, and hs-CRP levels, higher baseline adiponectin
      levels were associated with a lower relative risk (RR) of having type 2 (RR =
      0.07, confidence interval [CI]: 0.01-0.66, P = 0.021).Higher baseline adiponectin
      levels functioned as a predictor of a lower risk of developing type 2 diabetes
      mellitus among postmenopausal women during a 5.8 years follow-up study.
      Therefore, it is suggested that elevated adiponectin levels may offer protection
      against the development of type 2 diabetes mellitus after the menopause. 

PMID- 26287421
TI  - Evaluation of Dual Time Point Imaging 18F-FDG PET/CT in Differentiating
      Malignancy From Benign Gastric Disease.
AB  - To assess the clinical value of dual time point imaging (DTPI) fluorine
      18fludeoxyglucose (18F-FDG) positron emission tomography (PET)/CT in
      differentiating malignancy and benign disease of patients with focally increased
      gastric uptake.Patients who present focally increased 18F-FDG uptake in gastric
      wall on conventional PET/CT imaging received delayed imaging. PET/CT scans were
      acquired at 1 and 2 hours (early and delayed imaging) after 18F-FDG injection.
      The maximum standardized uptake value (SUV) was calculated. The SUVmax of the
      early and delayed imaging acquisition were signed S1 and S2, respectively. The
      receiver operating characteristic curve (ROC) of the S1, S2, and the retention
      index (RI) were drawn to find the best cut-off point value for differential
      diagnosis. Sensitivity, specificity, Youden index, and the area under the curve
      (AUC) were calculated, respectively.From September 2010 to May 2015, 74 patients
      (56 male and 18 female; age of 57 +/- 12 years; range, 32-86 years) referring for
      areas of focally increased uptake of 18F-FDG in gastric wall received delayed
      imaging. The S1 was 5.0 +/- 1.4 (range, 1.9-11.3), and S2 was 5.9 +/- 2.7 (range,
      1.0-16.3). The SUVmax were increased in 52 patients in delayed imaging, with 85%
      (44/52 cases) appeared malignant; decreased in 20 patients, and 90% (18/20 cases)
      were benign; 2 patients of benign had not changed. The change of SUVmax between
      malignant and benign was significant difference (t = -5.785, P = 0.000).Taking
      the S1, S2, and RI higher than 4.6%, 5.1%, and 13% as positive diagnostic
      criteria, the sensitivity were 65.2%,87.0%, and 87.0%, respectively; the
      specificity were 64.3%, 82.1%, and 89.3%; the Youden index were 0.332, 0.693, and
      0.770; AUC were 0.635 (95% confidence intervals (95% CI) 0.507-0.764), 0.873 (95%
      CI, 0.786-0.961), and 0.923 (95% CI, 0.854-0.992).DTPI is more precise to
      distinct malignant from benign gastric diseases compared with conventional
      imaging, and it is readily accessible. 

PMID- 26287422
TI  - Postoperative Fluid Overload is a Useful Predictor of the Short-Term Outcome of
      Renal Replacement Therapy for Acute Kidney Injury After Cardiac Surgery.
AB  - To analyze the predictive value of postoperative percent fluid overload (PFO) of
      renal replacement therapy (RRT) for acute kidney injury (AKI) patients after
      cardiac surgery.Data from 280 cardiac surgery patients between 2005 January and
      2012 April were collected for retrospective analyses. A receiver operating
      characteristic (ROC) curve was used to compare the predictive values of
      cumulative PFO at different times after surgery for 90-day mortality.The
      cumulative PFO before RRT initiation was 7.9% +/- 7.1% and the median PFO 6.1%.
      The cumulative PFO before and after RRT initiation in intensive care unit (ICU)
      was higher in the death group than in the survival group (8.8% +/- 7.6% vs 6.1%
      +/- 5.6%, P = 0.001; -0.5[-5.6, 5.1]% vs 6.9[2.2, 14.6]%, P < 0.001). The
      cumulative PFO during the whole ICU stay was 14.3% +/- 15.8% and the median PFO
      was 10.7%. The areas under the ROC curves to predict the 90-day mortality by PFO
      at 24 hours, cumulative PFO before and after RRT initiation, and PFO during the
      whole ICU stay postoperatively were 0.625, 0.627, 0.731, and 0.752. PFO during
      the whole ICU stay >=7.2% was determined as the cut-off point for 90-day
      mortality prediction with a sensitivity of 77% and a specificity of 64%. Kaplan
      Meier survival estimates showed a significant difference in survival among
      patients with cumulative PFO >= 7.2% and PFO < 7.2% after cardiac surgery (log
      rank P < 0.001).Postoperative cumulative PFO during the whole ICU stay >=7.2%
      would have an adverse effect on 90-day short-term outcome, which may provide a
      strategy for the volume control of AKI-RRT patients after cardiac surgery. 

PMID- 26287423
TI  - The Impact of Postoperative Complications on Survivals After Esophagectomy for
      Esophageal Cancer.
AB  - The aim of this study was to assess the impact of postoperative complications
      after esophagectomy on long-term outcome.The treatment of esophageal cancer has
      recently been improved; however, esophagectomy with thoracotomy and laparotomy
      carries considerable postoperative morbidity and mortality. The real impact of
      postoperative complications on overall survival is still under evaluation.A
      retrospective analysis was performed on patients with esophageal cancer who
      underwent esophagectomy with thoracotomy and laparotomy, with R0 or R1 resection
      between January 1997 and December 2012. Of 402 patients, we analyzed the
      following parameters 284 patients who could be followed up for over 5 years:
      stage of disease, neoadjuvant therapies, surgical approaches, surgical
      complications, postoperative medical complications, and overall and relapse-free
      survivals using medical records.Of the 284 patients, 64 (22.5%) had pneumonia, 55
      (19.4%) had anastomotic leakage, and 45 (15.8%) had recurrent laryngeal nerve
      paralysis (RLNP). Pneumonia had a significant negative impact on overall survival
      (P = 0.035); however, anastomotic leakage and RLNP did not affect overall
      survival. Multivariate analysis revealed that the presence of pneumonia was
      predictive of poorer overall survival; the multivariate hazard ratio was 1.456
      (95% confidence interval 1.020-2.079, P = 0.039).Pneumonia has a negative impact
      on overall survival after esophagectomy. Strategies to prevent pneumonia after
      esophagectomy should improve outcomes in this operation. 

PMID- 26287424
TI  - Association of Vitamin D Receptor Cdx-2 Polymorphism With Cancer Risk: A Meta
      Analysis.
AB  - Vitamin D receptor (VDR) Cdx-2 polymorphism (rs11568820) has been indicated to be
      associated to cancer susceptibility. However, published studies reported mixed
      results. This meta-analysis was conducted to get a more accurate estimation of
      the association between Cdx-2 polymorphism and cancer risk.We identified 25
      independent studies with a total of 34,018 subjects published prior to March
      2015. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to
      evaluate the susceptibility to cancer. Separate analyses were conducted on
      features of the population such as ethnicity, source of controls, and cancer
      types.Meta-analysis results showed that Cdx-2 polymorphism significantly
      increased cancer risk in the homozygous model in overall analysis. According to
      the further stratified analysis, significant association was found between Cdx-2
      variant and cancer risk in American-Africans in the homozygous, recessive, and
      dominant comparison models. However, no significant associations were found in
      Caucasians and Asians. When stratified by different cancer types, significant
      association was observed between Cdx-2 variant and an increased risk of
      colorectal cancer in the homozygous, recessive, and dominant models. In addition,
      ovarian cancer susceptibility increased based on the homozygous and dominant
      comparison models.Our study indicated that VDR Cdx-2 polymorphism was associated
      with an increased cancer risk, particularly in American-Africans, colorectal, and
      ovarian cancers. However, other factors may impact on the association. Further
      multicenter studies are needed to confirm the effects of Cdx-2 polymorphism on
      cancer susceptibility. 

PMID- 26287425
TI  - Clinical and Epidemiologic Features of Severe Viral Gastroenteritis in Children:
      A 3-Year Surveillance, Multicentered Study in Taiwan With Partial Rotavirus
      Immunization.
AB  - The global epidemiological landscape of childhood acute gastroenteritis (AGE) is
      changing after the introduction of 2 effective rotavirus vaccines in 2006. A
      comprehensive evaluation for viral etiology of childhood AGE in Taiwan, where
      rotavirus vaccination was provided by the private sector since 2006, is
      lacking.From 2009 to 2011, children younger than 5 years of age with AGE who were
      hospitalized at 3 sentinel hospitals were enrolled in this surveillance study.
      Stool specimens were tested for rotavirus, norovirus, enteric adenovirus, and
      astrovirus. The epidemiologic and clinical information was collected by
      questionnaire-based interviews and chart reviews.Viral agents were detected in
      1055 (37.5%) of 2810 subjects, with rotavirus (21.2%) being the leading cause of
      disease, followed by norovirus (14.9%), enteric adenovirus (3.74%), astrovirus
      (2.10%), and a mixture of at least 2 of 4 above-mentioned viruses (4.06%). The
      majority (56%) of the viral AGE occurred in children <2 years of age. Rotavirus
      and norovirus were detected more frequently in cool seasons (P < 0.0001 for
      both), whereas no seasonal variation was observed for adenovirus and astrovirus.
      Adult households with diarrhea and a Vesikari score >10 were independent factors
      respectively associated with an increased risk of norovirus (adjusted odds ratio
      [aOR] 9.034, P = 0.0003) and rotavirus (aOR, 3.284, P < 0.0001) infections.
      Rotavirus immunization and female gender were protective factors against
      rotavirus (aOR, 0.198, P < 0.0001) and astrovirus (aOR, 0.382, P = 0.0299)
      infections, respectively.Rotavirus and norovirus are the 2 most important viral
      agents of childhood AGE in Taiwan with partial rotavirus immunization. In
      addition, different enteric viruses are associated with distinct epidemiologic
      and clinical features.

PMID- 26287426
TI  - Thoracoscopic Approach for Repair of Diaphragmatic Hernia Occurring After
      Pediatric Liver Transplant.
AB  - Diaphragmatic hernias (DH) occurring after pediatric liver transplantation (LT)
      are rare. However, such complications have been previously reported in the
      literature and treatment has always been surgical repair via laparotomy. We
      report our experience of minimally invasive thoracoscopic approach for repair of
      DH occurring after LT in pediatric recipients.From April 2010 to December 2014, 7
      cases of DH were identified in pediatric LT recipient in Samsung Medical Center.
      Thoracoscopic repair was attempted in 3 patients. Patients' medical records were
      retrospectively reviewed.Case 1 was a 12-month-old boy, having received deceased
      donor LT for biliary atresia (BA) 5 months ago. He presented with dyspnea and
      left-sided DH was detected. Thoracoscopic repair was successfully done and the
      boy was discharged at postoperative day 7. Case 2 was a 13-month-old boy, having
      received deceased donor LT for BA 2 months ago. He presented with vomiting and
      right-sided DH was detected. Thoracoscopic repair was done along with primary
      repair of herniated small bowel that was perforated while attempting reduction
      into the peritoneal cavity. The boy recovered from the surgery without
      complications and was discharged on the 10th postoperative day. Case 3 was a 43
      month-old girl, having received deceased donor LT for Alagille syndrome 28 months
      ago. She was diagnosed with right-sided DH during steroid pulse therapy for acute
      rejection. Thoracoscopic repair was attempted but a segment of necrotic bowel was
      noticed along with bile colored pleural effusion and severe adhesion in the
      thoracic cavity. She received DH repair with small bowel resection and
      anastomosis via laparotomy.Thoracoscopic repair was attempted in 3 cases of DH
      occurring after LT in pediatric recipients. With experience and expertise in
      pediatric minimally invasive surgery, thoracoscopic approach is feasible in this
      rare population of patients. 

PMID- 26287427
TI  - Kite versus Ponseti Method in the Treatment of 235 Feet With Idiopathic Clubfoot:
      Results of a Single Romanian Medical Center.
AB  - Congenital idiopathic clubfoot (CC) represents the fifth common most congenital
      malformation which may be treated conservatively or by surgery. In this article,
      we present the results obtained in our clinic after conservative therapy
      performed with 2 methods.A total of 235 consecutive feet (161 patients) were
      conservatively treated using Kite (n = 129) and Ponseti method (n = 106). The
      Dimeglio score was determined before and at 6 months after treatment to compare
      the 2 methods. All of the patients were treated in their first week of life.CC
      was more frequently diagnosed in males (n = 93; 57.76%), bilaterality being seen
      in 45.96% of the patients (n = 74). Although before therapy the Dimeglio score
      was similar in both groups (P = 0.85), it was significantly improved in patients
      treated by Ponseti method (P = 0.005). Duration of therapy was also longer in
      patients from Kite versus Ponseti group (20 vs 11 weeks). Failure of orthopedic
      treatment was more frequent in Kite group (30.32% vs 8.49% of the patients) and
      the relapses rate at 6 months was also higher (35.65% vs 11.32%).The conservative
      method used to treat the CC should be adapted on the patient's age and Ponseti
      method seems to be the most effective type of treatment used for patients treated
      in their first week of life. Dimeglio score can be successfully used for
      evaluation of these children. This is the eighth published study that compare the
      efficacy of Kite versus Ponseti method.

PMID- 26287428
TI  - Acute Submandibular Swelling Complicating Arteriography With Iodide Contrast: A
      Case Report and Literature Review.
AB  - Iodide mumps is an uncommon condition induced by iodide-containing contrast. We
      present the first reported case of iodide mumps in mainland China, which occurred
      after carotid artery intervention.The patient, a 65-year-old Chinese male, had a
      history of dizziness, hypertension, diabetes, and right arm weakness. He had no
      history of allergies and had never previously received iodide-containing
      contrast. The patient's kidney function and other laboratory findings were
      normal. He underwent stenting of the left internal carotid artery (LICA) opening
      and received approximately 250 mL of a nonionic contrast agent (ioversol).
      Approximately 5 hours after angioplasty, bilateral local swellings were noted
      near the mandible; the masses were moderately firm and nontender.Iodide mumps was
      diagnosed in the patient. Intravenous dexamethasone (10 mg) was administered. The
      submandibular glands had shrunk by 11 hours after angioplasty, and they gradually
      became softer. The mandibular salivary glands had completely recovered by 5 days
      after surgery.Iodide mumps represents a rare late reaction to iodine-containing
      contrast media. This condition can occur in any patient receiving any iodinated
      contrast agent and may recur upon repeated exposure, but self-resolution can be
      expected within 2 weeks. All clinicians who use contrast media or iodide should
      be aware of this condition. 

PMID- 26287429
TI  - The Treatment Results of a Standard Algorithm for Choosing the Best Entry Vessel
      for Intravenous Port Implantation.
AB  - Vascular cutdown and echo guide puncture methods have its own limitations under
      certain conditions. There was no available algorithm for choosing entry vessel. A
      standard algorithm was introduced to help choose the entry vessel location
      according to our clinical experience and review of the literature. The goal of
      this study is to analyze the treatment results of the standard algorithm used to
      choose the entry vessel for intravenous port implantation.During the period
      between March 2012 and March 2013, 507 patients who received intravenous port
      implantation due to advanced chemotherapy were included into this study. Choice
      of entry vessel was according to standard algorithm. All clinical characteristic
      factors were collected and complication rate and incidence were further
      analyzed.Compared with our clinical experience in 2006, procedure-related
      complication rate declined from 1.09% to 0.4%, whereas the late complication rate
      decreased from 19.97% to 3.55%. No more pneumothorax, hematoma, catheter kinking,
      fractures, and pocket erosion were identified after using the standard algorithm.
      In alive oncology patients, 98% implanted port could serve a functional vascular
      access to fit therapeutic needs.This standard algorithm for choosing the best
      entry vessel is a simple guideline that is easy to follow. The algorithm has
      excellent efficiency and can minimize complication rates and incidence. 

PMID- 26287430
TI  - The Impact of Confluence Types of the Right Gastroepiploic Vein on No. 6
      Lymphadenectomy During Laparoscopic Radical Gastrectomy.
AB  - This study investigated anatomical variations in the confluence types of the
      right gastroepiploic vein (RGEV) to improve knowledge regarding no. 6
      lymphadenectomy for laparoscopic gastrectomy.The RGEV drainage patterns of 144
      patients who were diagnosed with gastric cancer and underwent laparoscopic distal
      gastrectomy at our department from July 2010 to June 2011 were prospectively
      collected and retrospectively analyzed, and we compared the impact of different
      drainage patterns on no. 6 lymphadenectomy.The RGEV confluence types were
      classified into 6 categories in this study. Types I, II, and III, which were
      observed in 53 (36.8%), 27 (18.8%), and 21 (14.6%) cases, respectively, were the
      most frequently found during gastrectomy. All 3 of these types included a
      gastropancreatic trunk and were defined as the gastropancreatic group (GP group).
      In addition, 15 cases (10.4%) were categorized as type IV, 19 (13.2%) were
      categorized as type V, and 9 (6.3%) were categorized as type VI. These 3 types,
      which could form a gastrocolic trunk, were defined as the gastrocolic group (GC
      group). No significant differences were found with respect to the
      clinicopathological characteristics, postoperative morbidity, perioperative
      mortality, and 3-year overall survival rates after surgery between the 2 groups
      (all P > 0.05). However, the mean no. 6 lymph node (No. 6 LN) dissection time,
      the mean blood loss due to No. 6 LN dissection and the rate of infrapyloric
      vascular injury were significantly increased in the GC group compared with the GP
      group (all P < 0.05).The RGEV exhibits 6 types of drainage patterns, and the
      division points of this vein during laparoscopic gastrectomy depend on the
      different drainage patterns. For types IV, V, and VI, the surgeon should
      carefully vascularize and divide the RGEV above its confluences during surgery. 

PMID- 26287431
TI  - Inconsistent Correlation Between Carotid Artery Intima-Media Thickness and
      Peripheral Arterial Tonometry: Brazilian Longitudinal Study of Adult Health (ELSA
      Brasil).
AB  - To estimate the association between 2 markers for atherosclerosis, measurements
      of carotid artery intima-media thickness (IMT) and of peripheral arterial
      tonometry (PAT), and to evaluate the role of traditional cardiovascular risk
      factors in this association.We applied the 2 diagnostic tests to 588 participants
      from the ELSA-Brazil longitudinal study cohort. The PAT measurements, obtained
      with the EndoPAT2000, were the reactive hyperemia index (RHI), the Framingham RHI
      (F-RHI), and the mean basal pulse amplitude (BPA). We used the mean of the mean
      scores of carotid IMT of the distal layers of the left and right common carotids
      obtained by ultrasonography after 3 cardiac cycles. We used linear regression and
      the Spearman correlation coefficient to test the relationship between the 2
      markers, and multiple linear regressions to exam the relationship between the
      RHI/F-RHI scores and the mean BPA and IMT scores after adjusting for
      cardiovascular risk factors.In the multivariate analysis, RHI (but not F-RHI) was
      positively correlated with the mean of the means of the IMT values after
      adjusting for sex and risk factors connected with both measures (beta = 0.05, P =
      0.02). Mean BPA did not remain significantly associated with IMT after adjusting
      for common risk factors.We found that the higher the IMT (or the worse the IMT),
      the higher the RHI (or the better the endothelial function). F-RHI was not
      associated with IMT. These 2 results are against the direction that one would
      expect and may imply that digital endothelial function (RHI and F-RHI) and IMT
      correspond to distinct and independent stages of the complex atherosclerosis
      process and represent different pathways in the disease's progression. Therefore,
      IMT and PAT measures may be considered complementary and not interchangeable. 

PMID- 26287432
TI  - Efficacy of Appropriate Antimicrobial Therapy on the Survival of Patients With
      Carbapenem Nonsusceptible Klebsiella Pneumoniae Infection: A Multicenter Study in
      Taiwan.
AB  - The impact of antimicrobial treatment on the outcome of carbapenem nonsusceptible
      Klebsiella pneumoniae (CnsKP) infections needs to be elucidated. This nationwide,
      multicenter study was conducted to evaluate the impact of appropriate
      antimicrobial therapy on 14-day mortality among patients with CnsKP infection in
      Taiwan.Patients with CnsKP infections from 11 medical centers and 4 regional
      hospitals in Taiwan were enrolled in 2013. Carbapenem nonsusceptibility was
      defined as a minimum inhibitory concentration of >=2 mg/L for imipenem or
      meropenem. Predictors of 14-day mortality were determined using the Cox
      proportional regression model. The influence of infection severity on the impact
      of appropriate use of antimicrobials on 14-day mortality was determined using the
      Acute Physiology and Chronic Health Evaluation (APACHE) II score.Overall 14-day
      mortality was 31.8% (49/154). Unadjusted mortality for appropriate antimicrobial
      therapy was 23.1% (18/78 patients). Appropriate therapy was independently
      associated with reduced mortality (hazard ratio [HR], 0.44; 95% confidence
      interval [CI], 0.24-0.80; P = 0.007). A subgroup analysis revealed that the
      benefit of appropriate therapy was limited to patients with higher APACHE II
      scores (HR for patients with scores >15 and <=35, 0.46; 95% CI 0.23-0.92; and for
      those with scores >35, 0.14; 95% CI, 0.02-0.99).In conclusion, appropriate
      antimicrobial therapy significantly reduces 14-day mortality for CnsKP
      infections. Survival benefit is more notable among more severely ill patients. 

PMID- 26287433
TI  - MK-801-induced deficits in social recognition in rats: reversal by aripiprazole,
      but not olanzapine, risperidone, or cannabidiol.
AB  - Deficiencies in social activities are hallmarks of numerous brain disorders. With
      respect to schizophrenia, social withdrawal belongs to the category of negative
      symptoms and is associated with deficits in the cognitive domain. Here, we used
      the N-methyl-D-aspartate receptor antagonist dizocilpine (MK-801) for induction
      of social withdrawal in rats and assessed the efficacy of several atypical
      antipsychotics with different pharmacological profiles as putative treatment. In
      addition, we reasoned that the marijuana constituent cannabidiol (CBD) may
      provide benefit or could be proposed as an adjunct treatment in combination with
      antipsychotics. Hooded Lister rats were tested in the three-chamber version for
      social interaction, with an initial novelty phase, followed after 3 min by a
      short-term recognition memory phase. No drug treatment affected sociability.
      However, distinct effects on social recognition were revealed. MK-801 reduced
      social recognition memory at all doses (>0.03 mg/kg). Predosing with aripiprazole
      dose-dependently (2 or 10 mg/kg) prevented the memory decline, but doses of 0.1
      mg/kg risperidone or 1 mg/kg olanzapine did not. Intriguingly, CBD impaired
      social recognition memory (12 and 30 mg/kg) but did not rescue the MK-801-induced
      deficits. When CBD was combined with protective doses of aripiprazole (CBD
      aripiprazole at 12 :  or 5 : 2 mg/kg) the benefit of the antipsychotic was lost.
      At the same time, activity-related changes in behaviour were excluded as
      underlying reasons for these pharmacological effects. Collectively, the combined
      activity of aripiprazole on dopamine D2 and serotonin 5HT1A receptors appears to
      provide a significant advantage over risperidone and olanzapine with respect to
      the rescue of cognitive deficits reminiscent of schizophrenia. The differential
      pharmacological properties of CBD, which are seemingly beneficial in human
      patients, did not back-translate and rescue the MK-801-induced social memory
      deficit.

PMID- 26287434
TI  - Prescription of "ineffective neuroprotective" drugs to stroke patients: a cross
      sectional study in North Indian population.
AB  - In a developing country, where patient access to tertiary care is limited and
      most patients have to pay out of pocket, it is imperative for the physicians to
      practice evidence-based medicine. Reports on prescription details and surveys are
      not available. The aim of this study is to describe the prescribing patterns for
      various medications used in the treatment of stroke among the first contact
      physicians in North India; to estimate the proportion of patients being
      prescribed the non-recommended drugs and to determine any relationship between
      the economic status of the patient and the prescription pattern. Details of
      economic status, education level, type of stroke, type of hospital, qualification
      of treating physician and the number and nature of medications were noted from
      the prescriptions and patients. Two hundred and sixteen patients with ischemic
      stroke (71.3% males, average age 51.5 years) were included. Among poor patients,
      N = (36.8%) received any of the neuroprotective drugs including citicoline 19
      (27.5%), piracetam 11(15.9%) and edaravone 2(2.9%). Both specialist and private
      hospitals are associated with higher prescription of "ineffective
      neuroprotective" drugs in both poor and rich patients. Reasons for
      overprescribing neuroprotective medications need to be studied and remedial
      measures need to be taken to practice evidence-based medicine. 

PMID- 26287435
TI  - Synthetic and Predictive Approach to Unsymmetrical Biphenols by Iron-Catalyzed
      Chelated Radical-Anion Oxidative Coupling.
AB  - An iron-catalyzed oxidative unsymmetrical biphenol coupling in 1,1,1,3,3,3
      hexafluoropropan-2-ol that proceeds via a chelated radical-anion coupling
      mechanism was developed. Based on mechanistic studies, electrochemical methods,
      and density functional theory calculations, we suggest a general model that
      enables prediction of the feasibility of cross-coupling for a given pair of
      phenols. 

PMID- 26287436
TI  - Supercharged fluorescent protein as a versatile probe for the detection of
      glycosaminoglycans in vitro and in vivo.
AB  - Glycosaminoglycans (GAGs) are linear acidic heteropolysaccharides that are
      ubiquitously expressed in animal tissues and participate in various life
      processes. To date, the detection and visualization of GAGs in complex biological
      samples and living organisms remain a challenge because of the lack of powerful
      biocompatible probes. In this study, a superpositively charged green fluorescent
      protein (ScGFP) was shown great potential in GAG detection for the first time.
      First, on the basis of the phenomenon of GAGs dose-dependently inhibiting the
      fluorescence quenching of ScGFP by graphene oxide, a simple and highly sensitive
      signal-on homogeneous platform was established for detecting and quantifying
      GAGs, even in complex samples such as heparin in citrated plasma and oversulfated
      chondroitin sulfate in heparin. Furthermore, ScGFP with excellent stability and
      biocompatibility could be easily used as a highly sensitive and selective probe
      to visualize different types of GAGs in vitro and in vivo through combination
      with specific GAG-degrading enzymes. This study introduces a versatile probe for
      GAG detection, which is easy to prepare and which shows a high practical value in
      basic research and medical applications. 

PMID- 26287437
TI  - Improved Ammonolytic Synthesis, Structure Determination, Electronic Structure,
      and Magnetic Properties of the Solid Solution Sn(x)Fe(4-x)N (0 <= x <= 0.9).
AB  - We report a synthetic and theoretical study of the solid solution Sn(x)Fe(4-x)N
      (0 <= x <= 0.9). A previously published ammonolytic synthesis was successfully
      modified to achieve the metastable nitrides in phase-pure quality out of many
      competing phases. As TG-DSC measurements show, the thermal stability of the
      nitrides increases with increasing tin content. The Sn(x)Fe(4-x)N series of
      compounds adopts an antiperovskite-like structure in space group Pm3m. Various
      experimental and theoretical methods provide evidence that the iron substitution
      by tin exclusively takes place at Wyckoff position 1a and leads to a Vegard-type
      behavior of the lattice parameter over the compositional range, with an expection
      for a small internal miscibility gap around Sn(0.33)Fe(3.67)N of unknown cause.
      For highly tin-substituted iron nitrides the composition was clarified by prompt
      gamma-ray activation analysis (PGAA) and determined as
      Sn(0.78(3))Fe(3.22(4))N(0.95(3)) evidencing a fully occupied nitrogen position.
      Magnetic measurements reveal a linear weakening of ferromagnetic interactions
      with increasing tin concentration.

PMID- 26287438
TI  - Asymmetric Construction of Spiro[thiopyranoindole-benzoisothiazole] Scaffold via
      a Formal [3 + 3] Spiroannulation.
AB  - An enantioselective formal thio[3 + 3] spiroannulation reaction of indoline-2
      thiones to 1-azadienes has been developed by the use of a quinine-derived
      bifunctional tertiary amine-thiourea catalyst, which furnished a series of
      optically active spiro[thiopyranoindole-benzoisothiazole] heterocycles with a
      spiro quaternary C-N/C-S stereogenic centers in high yields with good to
      excellent diastereo- and enantioselectivities. 

PMID- 26287439
TI  - Synthesis and structure-activity relationships for cytotoxicity and apoptosis
      inducing activity of (+)-halichonine B.
AB  - Halichonine B is a sesquiterpene alkaloid isolated from the marine sponge
      Halichondria okadai Kadota. Halichonine B has exhibited cytotoxicity against
      mammalian cancer cells and induced apoptosis in the human leukemia cell line
      HL60. Here we established a practical route for the synthesis of halichonine B
      and its analogues, and we evaluated their biological activities. It was revealed
      that the secondary amino groups in the side chain portion are important for the
      strong cytotoxicity of halichonine B and that the N(11)-prenyl group is
      unimportant. Halichonine B and its analogues were also observed to induce
      apoptosis in HL60 cells. 

PMID- 26287440
TI  - Private benefits and metabolic conflicts shape the emergence of microbial
      interdependencies.
AB  - Microbes perform many costly biological functions that benefit themselves, and
      may also benefit neighbouring cells. Losing the ability to perform such functions
      can be advantageous due to cost savings, but when they are essential for growth,
      organisms become dependent on ecological partners to compensate for those losses.
      When multiple functions may be lost, the ecological outcomes are potentially
      diverse, including independent organisms only; one-way dependency, where one
      partner performs all functions and others none; or mutual interdependency where
      partners perform complementary essential functions. What drives these different
      outcomes? We develop a model where organisms perform 'leaky' functions that
      provide both private and public benefits to explore the consequences of
      privatization level, costs and essentiality on influencing these outcomes. We
      show that mutual interdependency is favoured at intermediate levels of
      privatization for a broad range of conditions. One-way dependency, in contrast,
      is only favoured when privatization is low and loss-of-function benefits are
      accelerating. Our results suggest an interplay between privatization level and
      shape of benefits from loss in driving microbial dependencies. Given the ubiquity
      of microbial functions that are inevitably leaked and the ease of mutational
      inactivation, our findings may help to explain why microbial interdependencies
      are common in nature.

PMID- 26287441
TI  - Immunization of mice with a peptide derived from the HTLV-1 TAX1BP1 protein
      induces cross-reactive antibodies against aquaporin 4.
AB  - Antibodies against aquaporin-4 (AQP4) are specific and pathogenetic for
      Neuromyelitis Optica (NMO). In a previous study, three linear intracellular AQP4
      B-cell epitopes were uncovered in NMO patients. A particular epitope showed high
      sequence similarity with a segment of the human TAX1BP1 protein, which is
      necessary for the replication of HTLV-1 virus. The aim of the present study was
      to investigate whether immunization of mice with the TAX1BP1 peptide could
      produce specific antibodies against AQP4 epitopes or induce symptoms. Eight
      C57Bl/6 mice were immunized with TAX1BP1pep in Complete Freund's Adjuvant and
      eight with adjuvant only. Animals received three subcutaneous injections and sera
      were obtained before each immunization and at sacrifice. All sera were evaluated
      by ELISA for antibodies against the TAX1BP1peptide, the homologous AQP4 peptide
      and all linear AQP4 epitopes. Homologous and cross-inhibition assays were
      performed to ensure binding specificity, and reactivity against conformational
      AQP4 epitopes was evaluated by a cell-based assay. Sera from immunized animals
      showed high reactivity against the immunization peptide, and the homologous AQP4
      epitope. Inhibition assays confirmed binding specificity. No antibodies were
      produced against any other epitopes, either linear or conformational. No clinical
      or brain inflammatory signs were observed in the animals. The induction of
      antibodies to an AQP4 epitope in mice immunized with the TAX1BP1-derived peptide
      suggests that a latent HTLV-1 infection could lead to TAX1BP1 antigen
      presentation and the production of anti-AQP4 antibodies, probably through T cell
      mediated mechanisms. Further studies are needed for exploring triggering factors
      for NMO especially in HTLV-1-endemic regions.

PMID- 26287442
TI  - Rupturing C60 Molecules into Graphene-Oxide-like Quantum Dots: Structure,
      Photoluminescence, and Catalytic Application.
AB  - The large-scale synthesis of graphene-oxide-like quantum dots (GOLQDs) is
      reported by oxidizing C(60) molecules using a modified Hummers method with a
      yield of ~25 wt% readily achieved. The GOLQDs are highly soluble in water and in
      addition to hexagons have other carbon rings in the structure. They have an
      average height of ~1.2 nm and a diameter distribution of 0.6-2.2 nm after drying
      on substrates. First-principle calculations indicate that a possible rupturing
      route may include the insertion of oxygen atoms to C?C bonds in the C(60)
      molecule, followed by rupture of that C?C bonds. The GOLQD suspension has a
      strong photoluminescence (PL) with peak position dependent on excitation
      wavelength. The PL is related to the size and emissive traps caused by oxygen
      containing groups. The GOLQDs also catalyze the oxidation of benzyl alcohol with
      a high selectivity.

PMID- 26287443
TI  - Guidelines on the management and admission to intensive care of critically ill
      adult patients with haematological malignancy in the UK.

PMID- 26287444
TI  - Mindfulness and Modification Therapy for Behavioral Dysregulation: A Comparison
      Trial Focused on Substance Use and Aggression.
AB  - OBJECTIVES: Disorders of behavioral dysregulation often involve more than one
      dsyregulated behavior (e.g., drug abuse and aggression, alcohol abuse and
      gambling). The high co-occurrence suggests the need of a transdiagnostic
      treatment that can be customized to target multiple specific behaviors. METHOD:
      The current pilot study compared a 20-week, individual transdiagnostic therapy
      (mindfulness and modification therapy [MMT]) versus treatment as usual (TAU) in
      targeting alcohol problems, drug use, physical aggression, and verbal aggression
      in self-referred women. Assessments were administered at baseline, post
      intervention, and 2-month follow-up. RESULTS: Wilcoxon signed-ranked tests and
      multilevel modeling showed that MMT (n = 13) displayed (a) significant and large
      decreases in alcohol/drug use, physical aggression, and verbal aggression; (b)
      significantly greater decreases in alcohol/drug use and physical aggression than
      did TAU (n = 8); and (c) minimal-to-no deterioration of effects at follow-up.
      Both conditions showed significant decreases in verbal aggression, with no
      statistically significant difference between conditions. MMT also displayed
      greater improvements in mindfulness. CONCLUSIONS: Preliminary findings support
      the feasibility and efficacy of MMT in decreasing multiple dysregulated
      behaviors.

PMID- 26287445
TI  - Mechanical Evaluation of Locking, Nonlocking, and Hybrid Plating Constructs Using
      a Locking Compression Plate in a Canine Synthetic Bone Model.
AB  - OBJECTIVE: To evaluate the mechanical properties of locking screw placement in
      hybrid plating in comparison to all-locked and all nonlocked constructs. STUDY
      DESIGN: Completely randomized design. Forty-eight synthetic bone cylinders (4th
      generation composite Sawbones((r))) across 6 construct types (n = 8 each).
      METHODS: An 8-hole 3.5 mm LCP was placed across a 2 mm cylinder gap to mimic an
      unstable fracture model. The plates were secured with all locking screws, all
      nonlocking screws, or a combination of locking screws and nonlocking screws in
      the hybrid constructs. Constructs were cyclically tested nondestructively in 4
      point bending, axial compression, and torsion, and then tested to failure in
      torsion. The stiffness and strength of each construct were calculated and
      compared across construct types. RESULTS: Constructs with a locking screw located
      adjacent to the fracture gap were stiffer in bending and stronger in torsion to
      failure than constructs without an adjacent locking screw. Hybrid and nonlocking
      screw constructs more frequently failed by catastrophic breakage of the bone
      cylinder, compared to all locking screw constructs that failed by plastic
      deformation of the plate. CONCLUSIONS: Mechanical testing of synthetic bone model
      constructs shows that hybrid constructs are at least as stiff and strong as
      entirely nonlocked constructs, and with some screw configurations, are not
      statistically different from entirely locked constructs.

PMID- 26287446
TI  - Food protein-induced enterocolitis syndrome caused by fish and/or shellfish in
      Italy.
AB  - BACKGROUND: The study describes the demographic features, culprit foods, clinical
      features and outcomes for children presenting with acute fish and/or shellfish
      food protein-induced enterocolitis syndrome (FPIES) in four Italian paediatric
      allergy centres. METHODS: A retrospective/prospective study was undertaken. All
      children diagnosed with fish or shellfish FPIES were enrolled. The diagnosis of
      FPIES was based on Sicherer's or Miceli Sopo clinical criteria. Skin prick tests
      (SPT) were performed in all patients, at the time of diagnosis and prior to OFC.
      RESULTS: Seventy children were enrolled. Mean age at first episode was 14 months
      (range 6-46 months); mean age at diagnosis was 34 months (range 6-164 months).
      Sole and cod were the fish most commonly implicated. Fifty-seven of 70 (81%)
      children had FPIES exclusively to fish, 37 of 57 (65%) children had single-fish
      FPIES, 20 of 57 (35%) multiple-fish FPIES, nine of 70 (13%) presented adverse
      reactions exclusively to shellfish, and four of 70 (6%) presented adverse
      reactions to both fish and shellfish. Only four (5.7%) children presented
      episodes of acute FPIES with different foods (2 to cow's milk, 1 to egg, 1 to
      beef); in all cases, onset was prior to that of fish or shellfish FPIES. Fifteen
      of 70 (21%) children tolerated fish other than the offending fish. Twenty-four of
      70 (34%) children achieved tolerance (age range 24-102 months). CONCLUSIONS: The
      chief peculiarities of acute fish and shellfish FPIES, compared to more frequent
      cow's milk or soy FPIES, are (i) later age of onset, (ii) longer persistence and
      (iii) possibility of tolerating fish other than the offending fish. Adverse
      reactions with shellfish are possible.

PMID- 26287447
TI  - Bedforms as Biocatalytic Filters: A Pumping and Streamline Segregation Model for
      Nitrate Removal in Permeable Sediments.
AB  - Bedforms are a focal point of carbon and nitrogen cycling in streams and coastal
      marine ecosystems. In this paper, we develop and test a mechanistic model, the
      "pumping and streamline segregation" or PASS model, for nitrate removal in
      bedforms. The PASS model dramatically reduces computational overhead associated
      with modeling nitrogen transformations in bedforms and reproduces (within a
      factor of 2 or better) previously published measurements and models of
      biogeochemical reaction rates, benthic fluxes, and in-sediment nutrient and
      oxygen concentrations. Application of the PASS model to a diverse set of marine
      and freshwater environments indicates that (1) physical controls on nitrate
      removal in a bedform include the pore water flushing rate, residence time
      distribution, and relative rates of respiration and transport (as represented by
      the Damkohler number); (2) the biogeochemical pathway for nitrate removal is an
      environment-specific combination of direct denitrification of stream nitrate and
      coupled nitrification-denitrification of stream and/or sediment ammonium; and (3)
      permeable sediments are almost always a net source of dissolved inorganic
      nitrogen. The PASS model also provides a mechanistic explanation for previously
      published empirical correlations showing denitrification velocity (N2 flux
      divided by nitrate concentration) declines as a power law of nitrate
      concentration in a stream (Mulholland et al. Nature, 2008, 452, 202-205).

PMID- 26287449
TI  - Motional Resistance Evaluation of the Quartz Crystal Microbalance to Study the
      Formation of a Passive Layer in the Interfacial Region of a Copper|Diluted
      Sulfuric Solution.
AB  - A hyphenated technique based on vis-NIR spectroscopy and electrochemical quartz
      crystal microbalance with motional resistance monitoring was employed to
      investigate the dissolution of copper in acid media. Changes in motional
      resistance, current, mass, and absorbance during copper dissolution allow the
      evolution of the interfacial region of copper|diluted sulfuric solution to be
      understood. In particular, motional resistance is presented in this work as a
      useful tool to observe the evolution of the passive layer at the interface.
      During the forced copper electrodissolution in sulfuric solution, SO4(2-) favors
      the formation of soluble [Cu(H2O)6]2+. On the contrary, OH- involves the
      formation of Cu(H2O)4(OH)2, which precipitates on the electrode surface. The high
      viscosity and density of Cu(H2O)4(OH)2 formed on surface causes an increase in
      motional resistance independently of resonance frequency changes. During the
      copper corrosion in a more natural acidic environment, the results of
      electrochemical impedance spectra at open circuit potential indicate that
      corrosion is controlled by the diffusion of copper to the solution at short
      experimental times. However, copper diffusion is hindered by the formation of a
      passive layer on the electrode surface at long experimental times. During the
      copper corrosion, motional resistance shows an oscillatory response because of an
      oscillatory formation/dissolution of the passive later. Vis-NIR spectroscopy and
      electrochemical quartz crystal microbalance with motional resistance monitoring
      give new perspectives for reaching a deep understanding of metal corrosion
      processes and, in a future, other interfacial processes such as the catalysis or
      adsorption of (bio)molecules.

PMID- 26287451
TI  - Effects of Molecular Weight upon Irradiation-Cross-Linked Poly(vinyl
      alcohol)/Clay Aerogel Properties.
AB  - Facile fabrication of mechanically strong poly(vinyl alcohol) (PVOH)/clay aerogel
      composites through a combination of increasing polymer molecular weights and
      gamma irradiation-cross-linking is reported herein. The aerogels produced from
      high polymer molecular weights exhibit significantly increased compressive
      moduli, similar to the effect of irradiation-induced cross-linking. The required
      irradiation dose for fabricating strong PVOH composite aerogels with dense
      microstructure decreased with increasing polymer molecular weight. Neither
      thermal stability nor flammability was significantly changed by altering the
      polymer molecular weight or by modest gamma irradiation, but they were highly
      dependent upon the polymer/clay ratio in the aerogel. Optimization of the
      mechanical, thermal, and flammability properties of these composite aerogels
      could therefore be obtained by using relatively low levels of polymer, with very
      high polymer molecular weight, or lower molecular weight coupled with moderate
      gamma irradiation. The facile preparation of strong, low flammability aerogels is
      an alternative to traditional polymer foams in applications where fire safety is
      important. 

PMID- 26287450
TI  - Morphological and Immunohistochemical Characterization of Canine Osteosarcoma
      Spheroid Cell Cultures.
AB  - Spheroid cell culture emerges as powerful in vitro tool for experimental tumour
      research. In this study, we established a scaffold-free three-dimensional
      spheroid system built from canine osteosarcoma (OS) cells (D17). Spheroids (7, 14
      and 19 days of cultivation) and monolayer cultures (2 and 7 days of cultivation)
      were evaluated and compared on light and electron microscopy. Monolayer and
      spheroid cultures were tested for vimentin, cytokeratin, alkaline phosphatase,
      osteocalcin and collagen I by means of immunohistochemistry. The spheroid cell
      culture exhibited a distinct network of collagen I in particular after 19-day
      cultivation, whereas in monolayer cultures, collagen I was arranged as a lamellar
      basal structure. Necrotic centres of large spheroids, as observed in 14- and 19
      day cultures, were characterized by significant amounts of osteocalcin.
      Proliferative activity as determined by Ki-67 immunoreactivity showed an even
      distribution in two-dimensional cultures. In spheroids, proliferation was
      predominating in the peripheral areas. Metastasis-associated markers ezrin and
      S100A4 were shown to be continuously expressed in monolayer and spheroid
      cultures. We conclude that the scaffold-free spheroid system from canine OS cells
      has the ability to mimic the architecture of the in vivo tumour, in particular
      cell-cell and cell-matrix interactions. 

PMID- 26287452
TI  - Collaboration between mental health and employment services to support employment
      of individuals with mental disorders.
AB  - PURPOSE: The aim of this study was to investigate the extent of the
      interdisciplinary collaboration between mental health (MHS) professionals and
      social security professionals (SSI), their perceptions of this interdisciplinary
      collaboration and whether these perceptions differed between professionals of the
      two organizations. METHOD: We obtained data from mental health professionals and
      social security professionals in the context of a national agreement between MHS
      and SSI to improve the collaboration between MHS professionals and SSI
      professionals in the support of individuals with mental disorders to improve work
      outcome of these individuals. RESULTS: Mental health professionals as well as SSI
      professionals reported a moderate level of interdisciplinary collaboration, which
      does not seem to be affected by demographic variables, such as age, gender,
      profession and region. When professionals collaborated in a structural way they
      were more positive regarding their interdisciplinary collaboration with
      professionals of the other organization than professionals that collaborated in
      an ad hoc manner. CONCLUSIONS: Interdisciplinary collaboration was perceived as
      moderate by collaborating mental health professionals and social security
      professionals. In order to improve the collaboration between MHS and SSI on a
      local microlevel, organizations need to facilitate more structural collaboration
      between the professionals. IMPLICATIONS FOR REHABILITATION: Collaborating mental
      health professionals and social security professionals perceived their
      interdisciplinary collaboration as moderate. In order to improve the
      collaboration between mental health services (MHS) and vocational rehabilitation
      services on a local microlevel, organizations need to facilitate more structural
      collaboration between the professionals. Integrated services with the
      participation of MHS as well as vocational rehabilitation services, e.g. to share
      client information and to refer clients to each other, need to be developed. A
      national agreement between MHS and vocational rehabilitation services is a good
      starting point to improve collaboration between both the sectors.

PMID- 26287448
TI  - Negative childhood experiences alter a prefrontal-insular-motor cortical network
      in healthy adults: A preliminary multimodal rsfMRI-fMRI-MRS-dMRI study.
AB  - Research in humans and animals has shown that negative childhood experiences
      (NCE) can have long-term effects on the structure and function of the brain.
      Alterations have been noted in grey and white matter, in the brain's resting
      state, on the glutamatergic system, and on neural and behavioural responses to
      aversive stimuli. These effects can be linked to psychiatric disorder such as
      depression and anxiety disorders that are influenced by excessive exposure to
      early life stressors. The aim of the current study was to investigate the effect
      of NCEs on these systems. Resting state functional MRI (rsfMRI), aversion task
      fMRI, glutamate magnetic resonance spectroscopy (MRS), and diffusion magnetic
      resonance imaging (dMRI) were combined with the Childhood Trauma Questionnaire
      (CTQ) in healthy subjects to examine the impact of NCEs on the brain. Low CTQ
      scores, a measure of NCEs, were related to higher resting state glutamate levels
      and higher resting state entropy in the medial prefrontal cortex (mPFC). CTQ
      scores, mPFC glutamate and entropy, correlated with neural BOLD responses to the
      anticipation of aversive stimuli in regions throughout the aversion-related
      network, with strong correlations between all measures in the motor cortex and
      left insula. Structural connectivity strength, measured using mean fractional
      anisotropy, between the mPFC and left insula correlated to aversion-related
      signal changes in the motor cortex. These findings highlight the impact of NCEs
      on multiple inter-related brain systems. In particular, they highlight the role
      of a prefrontal-insular-motor cortical network in the processing and responsivity
      to aversive stimuli and its potential adaptability by NCEs.

PMID- 26287453
TI  - Autologous Serum Eye Drops Accelerate Epithelial Healing After LASEK.

PMID- 26287454
TI  - The Influence of Context on Health.

PMID- 26287456
TI  - Computational biology: How to catch rare cell types.

PMID- 26287457
TI  - Addendum: Plio-Pleistocene climate sensitivity evaluated using high-resolution
      CO2 records.

PMID- 26287459
TI  - Guiding the folding pathway of DNA origami.
AB  - DNA origami is a robust assembly technique that folds a single-stranded DNA
      template into a target structure by annealing it with hundreds of short 'staple'
      strands. Its guiding design principle is that the target structure is the single
      most stable configuration. The folding transition is cooperative and, as in the
      case of proteins, is governed by information encoded in the polymer sequence. A
      typical origami folds primarily into the desired shape, but misfolded structures
      can kinetically trap the system and reduce the yield. Although adjusting assembly
      conditions or following empirical design rules can improve yield, well-folded
      origami often need to be separated from misfolded structures. The problem could
      in principle be avoided if assembly pathway and kinetics were fully understood
      and then rationally optimized. To this end, here we present a DNA origami system
      with the unusual property of being able to form a small set of distinguishable
      and well-folded shapes that represent discrete and approximately degenerate
      energy minima in a vast folding landscape, thus allowing us to probe the assembly
      process. The obtained high yield of well-folded origami structures confirms the
      existence of efficient folding pathways, while the shape distribution provides
      information about individual trajectories through the folding landscape. We find
      that, similarly to protein folding, the assembly of DNA origami is highly
      cooperative; that reversible bond formation is important in recovering from
      transient misfoldings; and that the early formation of long-range connections can
      very effectively enforce particular folds. We use these insights to inform the
      design of the system so as to steer assembly towards desired structures.
      Expanding the rational design process to include the assembly pathway should thus
      enable more reproducible synthesis, particularly when targeting more complex
      structures. We anticipate that this expansion will be essential if DNA origami is
      to continue its rapid development and become a reliable manufacturing technology.

PMID- 26287460
TI  - Genetics: Location affects sporulation.

PMID- 26287458
TI  - Endosymbiotic origin and differential loss of eukaryotic genes.
AB  - Chloroplasts arose from cyanobacteria, mitochondria arose from proteobacteria.
      Both organelles have conserved their prokaryotic biochemistry, but their genomes
      are reduced, and most organelle proteins are encoded in the nucleus.
      Endosymbiotic theory posits that bacterial genes in eukaryotic genomes entered
      the eukaryotic lineage via organelle ancestors. It predicts episodic influx of
      prokaryotic genes into the eukaryotic lineage, with acquisition corresponding to
      endosymbiotic events. Eukaryotic genome sequences, however, increasingly
      implicate lateral gene transfer, both from prokaryotes to eukaryotes and among
      eukaryotes, as a source of gene content variation in eukaryotic genomes, which
      predicts continuous, lineage-specific acquisition of prokaryotic genes in
      divergent eukaryotic groups. Here we discriminate between these two alternatives
      by clustering and phylogenetic analysis of eukaryotic gene families having
      prokaryotic homologues. Our results indicate (1) that gene transfer from bacteria
      to eukaryotes is episodic, as revealed by gene distributions, and coincides with
      major evolutionary transitions at the origin of chloroplasts and mitochondria;
      (2) that gene inheritance in eukaryotes is vertical, as revealed by extensive
      topological comparison, sparse gene distributions stemming from differential
      loss; and (3) that continuous, lineage-specific lateral gene transfer, although
      it sometimes occurs, does not contribute to long-term gene content evolution in
      eukaryotic genomes. 

PMID- 26287461
TI  - Cell mixing induced by myc is required for competitive tissue invasion and
      destruction.
AB  - Cell-cell intercalation is used in several developmental processes to shape the
      normal body plan. There is no clear evidence that intercalation is involved in
      pathologies. Here we use the proto-oncogene myc to study a process analogous to
      early phase of tumour expansion: myc-induced cell competition. Cell competition
      is a conserved mechanism driving the elimination of slow-proliferating cells (so
      called 'losers') by faster-proliferating neighbours (so-called 'winners') through
      apoptosis and is important in preventing developmental malformations and maintain
      tissue fitness. Here we show, using long-term live imaging of myc-driven
      competition in the Drosophila pupal notum and in the wing imaginal disc, that the
      probability of elimination of loser cells correlates with the surface of contact
      shared with winners. As such, modifying loser-winner interface morphology can
      modulate the strength of competition. We further show that elimination of loser
      clones requires winner-loser cell mixing through cell-cell intercalation. Cell
      mixing is driven by differential growth and the high tension at winner-winner
      interfaces relative to winner-loser and loser-loser interfaces, which leads to a
      preferential stabilization of winner-loser contacts and reduction of clone
      compactness over time. Differences in tension are generated by a relative
      difference in F-actin levels between loser and winner junctions, induced by
      differential levels of the membrane lipid phosphatidylinositol (3,4,5)
      trisphosphate. Our results establish the first link between cell-cell
      intercalation induced by a proto-oncogene and how it promotes invasiveness and
      destruction of healthy tissues. 

PMID- 26287462
TI  - Ecology: Global trends in plant naturalization.

PMID- 26287464
TI  - Evolution: Gene transfer in complex cells.

PMID- 26287463
TI  - Sidekick 2 directs formation of a retinal circuit that detects differential
      motion.
AB  - In the mammalian retina, processes of approximately 70 types of interneurons form
      specific synapses on roughly 30 types of retinal ganglion cells (RGCs) in a
      neuropil called the inner plexiform layer. Each RGC type extracts salient
      features from visual input, which are sent deeper into the brain for further
      processing. The specificity and stereotypy of synapses formed in the inner
      plexiform layer account for the feature-detecting ability of RGCs. Here we
      analyse the development and function of synapses on one mouse RGC type, called
      the W3B-RGC. These cells have the remarkable property of responding when the
      timing of the movement of a small object differs from that of the background, but
      not when they coincide. Such cells, known as local edge detectors or object
      motion sensors, can distinguish moving objects from a visual scene that is also
      moving. We show that W3B-RGCs receive strong and selective input from an unusual
      excitatory amacrine cell type known as VG3-AC (vesicular glutamate transporter
      3). Both W3B-RGCs and VG3-ACs express the immunoglobulin superfamily recognition
      molecule sidekick 2 (Sdk2), and both loss- and gain-of-function studies indicate
      that Sdk2-dependent homophilic interactions are necessary for the selectivity of
      the connection. The Sdk2-specified synapse is essential for visual responses of
      W3B-RGCs: whereas bipolar cells relay visual input directly to most RGCs, the W3B
      RGCs receive much of their input indirectly, via the VG3-ACs. This non-canonical
      circuit introduces a delay into the pathway from photoreceptors in the centre of
      the receptive field to W3B-RGCs, which could improve their ability to judge the
      synchrony of local and global motion. 

PMID- 26287465
TI  - Corrigendum: Carbonic anhydrases, EPF2 and a novel protease mediate CO2 control
      of stomatal development.

PMID- 26287466
TI  - Global exchange and accumulation of non-native plants.
AB  - All around the globe, humans have greatly altered the abiotic and biotic
      environment with ever-increasing speed. One defining feature of the Anthropocene
      epoch is the erosion of biogeographical barriers by human-mediated dispersal of
      species into new regions, where they can naturalize and cause ecological,
      economic and social damage. So far, no comprehensive analysis of the global
      accumulation and exchange of alien plant species between continents has been
      performed, primarily because of a lack of data. Here we bridge this knowledge gap
      by using a unique global database on the occurrences of naturalized alien plant
      species in 481 mainland and 362 island regions. In total, 13,168 plant species,
      corresponding to 3.9% of the extant global vascular flora, or approximately the
      size of the native European flora, have become naturalized somewhere on the globe
      as a result of human activity. North America has accumulated the largest number
      of naturalized species, whereas the Pacific Islands show the fastest increase in
      species numbers with respect to their land area. Continents in the Northern
      Hemisphere have been the major donors of naturalized alien species to all other
      continents. Our results quantify for the first time the extent of plant
      naturalizations worldwide, and illustrate the urgent need for globally integrated
      efforts to control, manage and understand the spread of alien species. 

PMID- 26287467
TI  - Single-cell messenger RNA sequencing reveals rare intestinal cell types.
AB  - Understanding the development and function of an organ requires the
      characterization of all of its cell types. Traditional methods for visualizing
      and isolating subpopulations of cells are based on messenger RNA or protein
      expression of only a few known marker genes. The unequivocal identification of a
      specific marker gene, however, poses a major challenge, particularly if this cell
      type is rare. Identifying rare cell types, such as stem cells, short-lived
      progenitors, cancer stem cells, or circulating tumour cells, is crucial to
      acquire a better understanding of normal or diseased tissue biology. To address
      this challenge we first sequenced the transcriptome of hundreds of randomly
      selected cells from mouse intestinal organoids, cultured self-organizing
      epithelial structures that contain all cell lineages of the mammalian intestine.
      Organoid buds, like intestinal crypts, harbour stem cells that continuously
      differentiate into a variety of cell types, occurring at widely different
      abundances. Since available computational methods can only resolve more abundant
      cell types, we developed RaceID, an algorithm for rare cell type identification
      in complex populations of single cells. We demonstrate that this algorithm can
      resolve cell types represented by only a single cell in a population of randomly
      sampled organoid cells. We use this algorithm to identify Reg4 as a novel marker
      for enteroendocrine cells, a rare population of hormone-producing intestinal
      cells. Next, we use Reg4 expression to enrich for these rare cells and
      investigate the heterogeneity within this population. RaceID confirmed the
      existence of known enteroendocrine lineages, and moreover discovered novel
      subtypes, which we subsequently validated in vivo. Having validated RaceID we
      then applied the algorithm to ex vivo-isolated Lgr5-positive stem cells and their
      direct progeny. We find that Lgr5-positive cells represent a homogenous abundant
      population of stem cells mixed with a rare population of Lgr5-positive secretory
      cells. We envision broad applicability of our method for discovering rare cell
      types and the corresponding marker genes in healthy and diseased organs. 

PMID- 26287469
TI  - Determinants of disease severity in adults with epilepsy: Results from the
      Neurological Diseases and Depression Study.
AB  - BACKGROUND: Epilepsy severity has been recognized as a significant predictor of
      health-related quality of life in patients with epilepsy. However, clinical
      markers of epilepsy severity such as seizure frequency often fail to capture
      important aspects of the disease. This study investigates the factors associated
      with patient-reported severity of epilepsy, assessed by the Global Assessment of
      Severity of Epilepsy (GASE) scale in adults with epilepsy. METHODS: Data from a
      cohort of 250 patients consecutively enrolled in the Neurological Diseases and
      Depression Study (NEEDS) were used to assess the determinants of epilepsy
      severity as measured by the GASE scale. Multiple linear regression analyses were
      used to examine the mediation effect of clinical and sociodemographic
      characteristics on patients' ratings on the GASE scale. RESULTS: The mean age of
      the study participants was 39.8 (SD=14.9) years, of which 44.4% were male. About
      66.8% of the participants reported "not at all severe" or "a little severe"
      epilepsy, while 0.4% reported "extremely severe" epilepsy. One-year seizure
      freedom, number of antiseizure medications, medication side effects, depression,
      anxiety, and seizure-related disability were identified as significant
      determinants of patients' ratings of epilepsy severity. Seizure-related
      disability mediated the effects of 1-year seizure freedom, number of antiseizure
      medications, and medication side effects on epilepsy severity. CONCLUSION:
      Overall, patients with epilepsy who reported higher GASE scores were less likely
      to achieve 1-year seizure freedom and more likely to be on more antiseizure
      medications, experience more side effects from medication, endorse more
      depression and anxiety symptoms, and have increased self-reported seizure-related
      disability. The identified determinants of global, self-rated epilepsy severity
      can aid the design of appropriate interventions and support services for patients
      with severe epilepsy.

PMID- 26287468
TI  - Tet2 is required to resolve inflammation by recruiting Hdac2 to specifically
      repress IL-6.
AB  - Epigenetic modifiers have fundamental roles in defining unique cellular identity
      through the establishment and maintenance of lineage-specific chromatin and
      methylation status. Several DNA modifications such as 5-hydroxymethylcytosine
      (5hmC) are catalysed by the ten eleven translocation (Tet) methylcytosine
      dioxygenase family members, and the roles of Tet proteins in regulating chromatin
      architecture and gene transcription independently of DNA methylation have been
      gradually uncovered. However, the regulation of immunity and inflammation by Tet
      proteins independent of their role in modulating DNA methylation remains largely
      unknown. Here we show that Tet2 selectively mediates active repression of
      interleukin-6 (IL-6) transcription during inflammation resolution in innate
      myeloid cells, including dendritic cells and macrophages. Loss of Tet2 resulted
      in the upregulation of several inflammatory mediators, including IL-6, at late
      phase during the response to lipopolysaccharide challenge. Tet2-deficient mice
      were more susceptible to endotoxin shock and dextran-sulfate-sodium-induced
      colitis, displaying a more severe inflammatory phenotype and increased IL-6
      production compared to wild-type mice. IkappaBzeta, an IL-6-specific
      transcription factor, mediated specific targeting of Tet2 to the Il6 promoter,
      further indicating opposite regulatory roles of IkappaBzeta at initial and
      resolution phases of inflammation. For the repression mechanism, independent of
      DNA methylation and hydroxymethylation, Tet2 recruited Hdac2 and repressed
      transcription of Il6 via histone deacetylation. We provide mechanistic evidence
      for the gene-specific transcription repression activity of Tet2 via histone
      deacetylation and for the prevention of constant transcription activation at the
      chromatin level for resolving inflammation. 

PMID- 26287471
TI  - Catalytic transfer hydrogenation and anticancer activity of arene-ruthenium
      compounds incorporating bi-dentate precursors.
AB  - Ruthenium based organometallic compounds are presently a subject of great
      attention as anticancer drugs and appear to work reasonably well on tumor cells.
      We develop a series of mononuclear arene-ruthenium compounds incorporating N,O
      and N,N bidentate ligands, and their activity as anticancer drugs against human
      hormone-refractory metastatic prostate cancer (HRMPCs) cell lines are
      investigated. The ruthenium compounds also act as effective catalysts in the
      transfer hydrogenation of the -C[double bond, length as m-dash]O- -> -CH(OH)-
      system. Three types of ligands, namely, sodium glutamate, C4H3NH(2-CH2NH(t)Bu),
      and C4H3NH(2-CH[double bond, length as m-dash]NR) are separately coupled with
      [(eta(6)-cymene)RuCl2]2 () (cymene = 4-isopropyltoluene) to synthesize five Ru
      derivatives: [(eta(6)-cymene)RuCl(kappa(2)-N,O-OOCCHNH2CH2CH2COOH)] (), {(eta(6)
      cymene)RuCl[C4H3N(2-CH2NH(t)Bu)]} (), {(eta(6)-cymene)RuCl[C4H3N(2-CH[double
      bond, length as m-dash]NCH2Ph)]} (), {(eta(6)-cymene)RuCl{C4H3N[2-CH[double bond,
      length as m-dash]NCH2(C4H7O)]}} () and {(eta(6)-cymene)RuCl[C4H3N(2
      CH(n)BuNHCH2(C4H7O))]} (). To the best of our knowledge, the aforementioned Ru
      compounds are not only characterized by (1)H and (13)C NMR spectroscopy, but for
      the first time their structures have been established by single crystal X-ray
      diffractometry. Compound influences a concentration-dependent apoptosis in PC-3
      cells and initiates the conversion rate in transfer hydrogenation. 

PMID- 26287470
TI  - Near-Infrared Fluorescence Lymphatic Imaging in Lymphangiomatosis.
AB  - BACKGROUND: Lymphangiomatosis is a rare disorder of the lymphatic system that can
      impact the dermis, soft tissue, bone, and viscera and can be characterized by
      lymphangiomas, swelling, and chylous discharge. Whether disordered
      lymphangiogenesis in lymphangiomatosis affects the function and anatomy of the
      entire systemic lymphatic circulation or is localized to specific sites is not
      fully known. METHODS AND RESULTS: A 35-year-old Caucasian female diagnosed with
      whole-body lymphangiomatosis at 2 months of age and who continues to present with
      progressive disease was imaged with near-infrared fluorescence lymphatic imaging.
      While the peripheral lymphatics in the extremities appeared largely normal
      compared to prior studies, we observed tortuous lymphatic vessels, fluorescence
      drainage from the peripheral lymphatics into lymphangiomas, and extensive dermal
      lymphatics in the left thigh and inguinal regions where the subject had
      previously had surgical assaults, potentially indicating defective systemic
      lymphangiogenesis. CONCLUSIONS: Further research into anatomical and functional
      lymphatic changes associated with the progression and treatment of
      lymphangiomatosis could aid in understanding the pathophysiology of the disease
      as well as point to treatment strategies.

PMID- 26287472
TI  - Elderly Man With 1-Month History of Flank and Abdominal Pain.

PMID- 26287473
TI  - An innovative pre-targeting strategy for tumor cell specific imaging and therapy.
AB  - A programmed pre-targeting system for tumor cell imaging and targeting therapy
      was established based on the "biotin-avidin" interaction. In this programmed
      functional system, transferrin-biotin can be actively captured by tumor cells
      with the overexpression of transferrin receptors, thus achieving the pre
      targeting modality. Depending upon avidin-biotin recognition, the attachment of
      multivalent FITC-avidin to biotinylated tumor cells not only offered the rapid
      fluorescence labelling, but also endowed the pre-targeted cells with targeting
      sites for the specifically designed biotinylated peptide nano-drug. Owing to the
      successful pre-targeting, tumorous HepG2 and HeLa cells were effectively
      distinguished from the normal 3T3 cells via fluorescence imaging. In addition,
      the self-assembled peptide nano-drug resulted in enhanced cell apoptosis in the
      observed HepG2 cells. The tumor cell specific pre-targeting strategy is
      applicable for a variety of different imaging and therapeutic agents for tumor
      treatments. 

PMID- 26287474
TI  - Coupled nonlinear oscillation and stability evolution of viscoelastic dielectric
      elastomers.
AB  - This article describes the development of an analytical model to study the
      coupled nonlinear oscillation and stability evolution of viscoelastic dielectric
      elastomers (DEs) under non-equibiaxial tensile forces by utilizing the method of
      virtual work. Numerically calculated results are employed to predict this
      nonlinear dynamic behavior. The resonant frequency (where the amplitude-frequency
      response curve peaks) and the amplitude-frequency response of the deformation in
      both in-plane directions are tuned by varying the values of tensile force. The
      oscillation response in the two in-plane directions exhibits strong nonlinearity
      and coupling with each other, and is tuned by the changing tensile forces under a
      specific excitation frequency. By varying the values of tensile forces, the
      dynamic viscoelastic creep in a certain in-plane direction can be eliminated.
      Phase diagrams and Poincare maps under several values of tensile forces are
      utilized to study the stability evolution of the DE system under non-equibiaxial
      tensile forces. 

PMID- 26287475
TI  - Growth-Curve Modeling of Nevi With a Peripheral Globular Pattern.
AB  - Importance: Although nevi with a peripheral rim of globules (peripheral globular
      nevi [PGN]) observed with dermoscopy are associated with enlarging melanocytic
      nevi, their actual growth dynamics remain unknown. Because change is a sensitive
      but nonspecific marker for melanoma, beginning to understand the growth patterns
      of nevi may improve the ability of physicians to differentiate normal from
      abnormal growth and reduce unnecessary biopsies. Objective: To study the growth
      dynamics and morphologic evolution of PGN on dermoscopy. Design, Setting, and
      Participants: A total of 84 participants with 121 PGN from September 1, 1999,
      through May 1, 2013, were identified retrospectively. Cohorts were recruited from
      the Memorial Sloan Kettering Cancer Center; Melanoma Unit of the Hospital Clinic,
      University of Barcelona; and Study of Nevi in Children. All 3 cohorts underwent
      longitudinal monitoring with serial dermoscopic imaging of their PGN. Data
      analysis was performed from May 1, 2014, through April 1, 2015. Main Outcomes and
      Measures: Establishment of the natural growth curve of PGN. The secondary aim was
      to establish the median time to growth cessation in those PGN for which the size
      eventually stabilized and/or had begun to decrease during the study period.
      Results: The median duration of follow-up was 25.1 (range, 2.0-114.4) months.
      Most of the nevi (116 [95.9%]) enlarged at some point during sequential
      monitoring. The rate of increase in the surface area of PGN varied among cohorts
      and ranged from -0.47 to 2.26 mm2/mo (mean rate, 0.25 [95% CI, 0.14-0.36]
      mm2/mo). The median time to growth cessation in the 26 PGN that stabilized or
      decreased in size (21.5%) was 58.6 months. All lesions changed in a symmetric
      manner and 91 (75.2%) displayed a decrease in the density of peripheral globules
      over time. Conclusions and Relevance: Nevi displaying a peripheral globular
      pattern enlarged symmetrically with apparent growth cessation occurring during a
      span of 4 to 5 years. Our results reiterate the important concept that not all
      growth is associated with malignancy.

PMID- 26287476
TI  - A case of postmenopausal androgen excess.
AB  - Ovarian steroid cell tumors are very rare but potentially life-threatening
      neoplasms. They represent less than 0.1% of all ovarian tumors, typically present
      in premenopausal women and frequently manifest with virilization. Signs of
      hyperandrogenism may appear in postmenopausal women due to tumoromicronus and non
      tumoromicronus adrenal and ovarian causes as well due to the normal aging
      process. In any case, steroid cell tumor should be suspected in postmenopausal
      women who present with rapid progressive androgen excess symptoms. This report
      describes a case of a 67-year-old postmenopausal woman with signs of
      hyperandrogenism, where an ovarian steroid cell tumor was diagnosed and treated
      by laparoscopic bilateral salpingo-oophorectomy and synchronous hysterectomy. 

PMID- 26287477
TI  - Centrosome age regulates kinetochore-microtubule stability and biases chromosome
      mis-segregation.
AB  - The poles of the mitotic spindle contain one old and one young centrosome. In
      asymmetric stem cell divisions, the age of centrosomes affects their behaviour
      and their probability to remain in the stem cell. In contrast, in symmetric
      divisions, old and young centrosomes are thought to behave equally. This
      hypothesis is, however, untested. In this study, we show in symmetrically
      dividing human cells that kinetochore-microtubules associated to old centrosomes
      are more stable than those associated to young centrosomes, and that this
      difference favours the accumulation of premature end-on attachments that delay
      the alignment of polar chromosomes at old centrosomes. This differential
      microtubule stability depends on cenexin, a protein enriched on old centrosomes.
      It persists throughout mitosis, biasing chromosome segregation in anaphase by
      causing daughter cells with old centrosomes to retain non-disjoint chromosomes
      85% of the time. We conclude that centrosome age imposes via cenexin a functional
      asymmetry on all mitotic spindles. 

PMID- 26287478
TI  - Orchestration of microtubules and the actin cytoskeleton in trichome cell shape
      determination by a plant-unique kinesin.
AB  - Microtubules (MTs) and actin filaments (F-actin) function cooperatively to
      regulate plant cell morphogenesis. However, the mechanisms underlying the
      crosstalk between these two cytoskeletal systems, particularly in cell shape
      control, remain largely unknown. In this study, we show that introduction of the
      MyTH4-FERM tandem into KCBP (kinesin-like calmodulin-binding protein) during
      evolution conferred novel functions. The MyTH4 domain and the FERM domain in the
      N-terminal tail of KCBP physically bind to MTs and F-actin, respectively. During
      trichome morphogenesis, KCBP distributes in a specific cortical gradient and
      concentrates at the branching sites and the apexes of elongating branches, which
      lack MTs but have cortical F-actin. Further, live-cell imaging and genetic
      analyses revealed that KCBP acts as a hub integrating MTs and actin filaments to
      assemble the required cytoskeletal configuration for the unique, polarized
      diffuse growth pattern during trichome cell morphogenesis. Our findings provide
      significant insights into the mechanisms underlying cytoskeletal regulation of
      cell shape determination. 

PMID- 26287479
TI  - GLO-Roots: an imaging platform enabling multidimensional characterization of soil
      grown root systems.
AB  - Root systems develop different root types that individually sense cues from their
      local environment and integrate this information with systemic signals. This
      complex multi-dimensional amalgam of inputs enables continuous adjustment of root
      growth rates, direction, and metabolic activity that define a dynamic physical
      network. Current methods for analyzing root biology balance physiological
      relevance with imaging capability. To bridge this divide, we developed an
      integrated-imaging system called Growth and Luminescence Observatory for Roots
      (GLO-Roots) that uses luminescence-based reporters to enable studies of root
      architecture and gene expression patterns in soil-grown, light-shielded roots. We
      have developed image analysis algorithms that allow the spatial integration of
      soil properties, gene expression, and root system architecture traits. We propose
      GLO-Roots as a system that has great utility in presenting environmental stimuli
      to roots in ways that evoke natural adaptive responses and in providing tools for
      studying the multi-dimensional nature of such processes. 

PMID- 26287480
TI  - DNA damage induces nuclear actin filament assembly by Formin -2 and Spire-1/2
      that promotes efficient DNA repair. [corrected].
AB  - Actin filaments assemble inside the nucleus in response to multiple cellular
      perturbations, including heat shock, protein misfolding, integrin engagement, and
      serum stimulation. We find that DNA damage also generates nuclear actin filaments
      detectable by phalloidin and live-cell actin probes-with three characteristic
      morphologies: (i) long, nucleoplasmic filaments; (ii) short, nucleolus-associated
      filaments; and (iii) dense, nucleoplasmic clusters. This DNA damage-induced
      nuclear actin assembly requires two biologically and physically linked nucleation
      factors: Formin-2 and Spire-1/Spire-2. Formin-2 accumulates in the nucleus after
      DNA damage, and depletion of either Formin-2 or actin's nuclear import factor,
      importin-9, increases the number of DNA double-strand breaks (DSBs), linking
      nuclear actin filaments to efficient DSB clearance. Nuclear actin filaments are
      also required for nuclear oxidation induced by acute genotoxic stress. Our
      results reveal a previously unknown role for nuclear actin filaments in DNA
      repair and identify the molecular mechanisms creating these nuclear filaments. 

PMID- 26287482
TI  - Molecular Design of Bisphosphonate-Modified Proteins for Efficient Bone Targeting
      In Vivo.
AB  - To establish a rational molecular design for bisphosphonate (BP)-modified
      proteins for efficient bone targeting, a pharmacokinetic study was performed
      using a series of alendronate (ALN), a nitrogen-containing BP, modified proteins
      with various molecular weights and varying degrees of modification. Four proteins
      with different molecular weight-yeast glutathione reductase (GR; MW: 112,000 Da),
      bovine serum albumin (BSA; MW: 67,000 Da), recombinant human superoxide dismutase
      (SOD; MW: 32,000 Da), and chicken egg white lysozyme (LZM; MW: 14,000 Da)-were
      modified with ALN to obtain ALN-modified proteins. Pharmacokinetic analysis of
      the tissue distribution of the ALN-modified and unmodified proteins was performed
      after radiolabeling them with indium-111 (111In) by using a bifunctional
      chelating agent. Calculation of tissue uptake clearances revealed that the bone
      uptake clearances of 111In-ALN-modified proteins were proportional to the degree
      of ALN modification. 111In-GR-ALN and BSA-ALN, the two high-molecular-weight
      proteins, efficiently accumulated in bones, regardless of the degree of ALN
      modification. Approximately 36 and 34% of the dose, respectively, was calculated
      to be delivered to the bones. In contrast, the maximum amounts taken up by bone
      were 18 and 13% of the dose for 111In-SOD-ALN(32) and LZM-ALN(9), respectively,
      because of their high renal clearance. 111In-SOD modified with both polyethylene
      glycol (PEG) and ALN (111In-PEG-SOD-ALN) was efficiently delivered to the bone.
      Approximately 36% of the dose was estimated to be delivered to the bones. In an
      experimental bone metastasis mouse model, treatment with PEG-SOD-ALN
      significantly reduced the number of tumor cells in the bone of the mice. These
      results indicate that the combination of PEG and ALN modification is a promising
      approach for efficient bone targeting of proteins with a high total-body
      clearance. 

PMID- 26287481
TI  - Expression and Cellular Localization of 15-Hydroxy-Prostaglandin-Dehydrogenase in
      Abdominal Aortic Aneurysm.
AB  - PGE2 has been implicated in abdominal aortic aneurysm (AAA) associated
      hypervascularization. PGE2-metabolism involves 15-hydroxyprostaglandin
      dehydrogenase (15-PGDH) the expression of which in AAA is unknown. The aim of
      this study was to examine the expression and cell distribution of 15-PGDH in AAA.
      Here, we show that 15-PGDH mRNA levels were significantly higher in aorta samples
      from patients undergoing AAA repair than in those from healthy multiorgan donors.
      Consequently, the ratio of metabolized PGE2 secreted by aortic samples was
      significantly higher in AAA. AAA production of total PGE2 and PGE2 metabolites
      correlated positively with PGI2 production, while the percentage of metabolized
      PGE2 correlated negatively with the total amount of PGE2 and with PGI2.
      Transcript levels of 15-PGDH were statistically associated with leukocyte markers
      but did not correlate with microvascular endothelial cell markers.
      Immunohistochemistry revealed 15-PGDH in the areas of leukocyte infiltration in
      AAA samples, mainly associated with CD45-positive cells, but not in normal aorta
      samples. We provide new data concerning 15-PGDH expression in human AAA, showing
      that 15-PGDH is upregulated in AAA and mainly expressed in infiltrating
      leukocytes. Our data suggest that microvasculature was not involved in PGE2
      catabolism, reinforcing the potential role of microvasculature derived PGE2 in
      AAA-associated hypervascularization. 

PMID- 26287483
TI  - Fluorescent mimics of cholesterol that rapidly bind surfaces of living mammalian
      cells.
AB  - Mammalian cells acquire cholesterol, a critical membrane constituent, through
      multiple mechanisms. We synthesized mimics of cholesterol, fluorescent N-alkyl
      3beta-cholesterylamine-glutamic acids, that are rapidly incorporated into
      cellular plasma membranes compared with analogous cholesteryl amides, ethers,
      esters, carbamates, and a sitosterol analogue. This process was inhibited by
      ezetimibe, indicating a receptor-mediated uptake pathway. 

PMID- 26287484
TI  - Correction: Effect of Introducing Xpert MTB/RIF to Test and Treat Individuals at
      Risk of Multidrug-Resistant Tuberculosis in Kazakhstan: A Prospective Cohort
      Study.

PMID- 26287485
TI  - Correction: Modeling of Beta Diversity in Tunisian Waters: Predictions Using
      Generalized Dissimilarity Modeling and Bioregionalisation Using Fuzzy Clustering.

PMID- 26287486
TI  - Integrated Paleoenvironmental Reconstruction and Taphonomy of a Unique Upper
      Cretaceous Vertebrate-Bearing Locality (Velaux, Southeastern France).
AB  - The Velaux-La Bastide Neuve fossil-bearing site (Bouches-du-Rhone, France) has
      yielded a diverse vertebrate assemblage dominated by dinosaurs, including the
      titanosaur Atsinganosaurus velauciensis. We here provide a complete inventory of
      vertebrate fossils collected during two large-scale field campaigns. Numerous
      crocodilian teeth occur together with complete skulls. Pterosaur, hybodont shark
      and fish elements are also represented but uncommon. Magnetostratigraphic
      analyses associated with biostratigraphic data from dinosaur eggshell and
      charophytes suggest a Late Campanian age for the locality. Lithologic and
      taphonomic studies, associated with microfacies and palynofacies analyses,
      indicate a fluvial setting of moderate energy with broad floodplain. Palynomorphs
      are quite rare; only three taxa of pollen grains occur: a bisaccate taxon, a
      second form probably belonging to the Normapolles complex, and another
      tricolporate taxon. Despite the good state of preservation, these taxa are
      generally difficult to identify, since they are scarce and have a very minute
      size. Most of the vertebrate remains are well preserved and suggest transport of
      the carcasses over short distances before accumulation in channel and overbank
      facies, together with reworked Aptian grains of glauconite, followed by a rapid
      burial. The bones accumulated in three thin layers that differ by their
      depositional modes and their taphonomic histories. Numerous calcareous and iron
      oxides-rich paleosols developed on the floodplain, suggesting an alternating dry
      and humid climate in the region during the Late Campanian. 

PMID- 26287489
TI  - Attention-Seeking Displays.
AB  - Animal communication abounds with extravagant displays. These signals are usually
      interpreted as costly signals of quality. However, there is another important
      function for these signals: to call the attention of the receiver to the
      signaller. While there is abundant empirical evidence to show the importance of
      this stage, it is not yet incorporated into standard signalling theory. Here I
      investigate a general model of signalling - based on a basic action-response game
      - that incorporates this searching stage. I show that giving attention-seeking
      displays and searching for them can be an ESS. This is a very general result and
      holds regardless whether only the high quality signallers or both high and low
      types give them. These signals need not be costly at the equilibrium and they
      need not be honest signals of any quality, as their function is not to signal
      quality but simply to call the attention of the potential receivers. These kind
      of displays are probably more common than their current weight in the literature
      would suggest. 

PMID- 26287487
TI  - Genetic Ablation of CD38 Protects against Western Diet-Induced Exercise
      Intolerance and Metabolic Inflexibility.
AB  - Nicotinamide adenine dinucleotide (NAD+) is a key cofactor required for essential
      metabolic oxidation-reduction reactions. It also regulates various cellular
      activities, including gene expression, signaling, DNA repair and calcium
      homeostasis. Intracellular NAD+ levels are tightly regulated and often respond
      rapidly to nutritional and environmental changes. Numerous studies indicate that
      elevating NAD+ may be therapeutically beneficial in the context of numerous
      diseases. However, the role of NAD+ on skeletal muscle exercise performance is
      poorly understood. CD38, a multi-functional membrane receptor and enzyme,
      consumes NAD+ to generate products such as cyclic-ADP-ribose. CD38 knockout mice
      show elevated tissue and blood NAD+ level. Chronic feeding of high-fat, high
      sucrose diet to wild type mice leads to exercise intolerance and reduced
      metabolic flexibility. Loss of CD38 by genetic mutation protects mice from diet
      induced metabolic deficit. These animal model results suggest that elevation of
      tissue NAD+ through genetic ablation of CD38 can profoundly alter energy
      homeostasis in animals that are maintained on a calorically-excessive Western
      diet. 

PMID- 26287488
TI  - Brain Regions Associated to a Kinesthetic Illusion Evoked by Watching a Video of
      One's Own Moving Hand.
AB  - It is well known that kinesthetic illusions can be induced by stimulation of
      several sensory systems (proprioception, touch, vision...). In this study we
      investigated the cerebral network underlying a kinesthetic illusion induced by
      visual stimulation by using functional magnetic resonance imaging (fMRI) in
      humans. Participants were instructed to keep their hand still while watching the
      video of their own moving hand (Self Hand) or that of someone else's moving hand
      (Other Hand). In the Self Hand condition they experienced an illusory sensation
      that their hand was moving whereas the Other Hand condition did not induce any
      kinesthetic illusion. The contrast between the Self Hand and Other Hand
      conditions showed significant activation in the left dorsal and ventral premotor
      cortices, in the left Superior and Inferior Parietal lobules, at the right
      Occipito-Temporal junction as well as in bilateral Insula and Putamen. Most
      strikingly, there was no activation in the primary motor and somatosensory
      cortices, whilst previous studies have reported significant activation in these
      regions for vibration-induced kinesthetic illusions. To our knowledge, this is
      the first study that indicates that humans can experience kinesthetic perception
      without activation in the primary motor and somatosensory areas. We conclude that
      under some conditions watching a video of one's own moving hand could lead to
      activation of a network that is usually involved in processing copies of
      efference, thus leading to the illusory perception that the real hand is indeed
      moving. 

PMID- 26287491
TI  - Multistakeholder Perspectives on the Transition to a Graduate-Level Athletic
      Training Educational Model.
AB  - CONTEXT: The decision has been made to move away from the traditional bachelor's
      degree professional program to a master's degree professional program. Little is
      known about the perceptions about this transition from those involved with
      education. OBJECTIVE: To examine multiple stakeholders' perspectives within
      athletic training education on the effect that a change to graduate-level
      education could have on the profession and the educational and professional
      development of the athletic trainer. DESIGN: Qualitative study. SETTING: Web
      based survey. PATIENTS OR OTHER PARTICIPANTS: A total of 18 athletic training
      students (6 men, 12 women; age = 24 +/- 5 years), 17 athletic training faculty (6
      men, 9 women, 2 unspecified; 7 program directors, 5 faculty members, 3 clinical
      coordinators, 2 unidentified; age = 45 +/- 8 years), and 15 preceptors (7 men, 7
      women, 1 unspecified; age = 34 +/- 7 years) completed the study. DATA COLLECTION
      AND ANALYSIS: Participants completed a structured Web-based questionnaire. Each
      cohort responded to questions matching their roles within an athletic training
      program. Data were analyzed following a general inductive process. Member checks,
      multiple-analyst triangulation, and peer review established credibility. RESULTS:
      Thirty-one (62%) participants supported the transition, 14 (28%) were opposed,
      and 5 (10%) were neutral or undecided. Advantages of and support for
      transitioning and disadvantages of and against transitioning emerged. The first
      higher-order theme, advantages, revealed 4 benefits: (1) alignment of athletic
      training with other health care professions, (2) advanced coursework and
      curriculum delivery, (3) improved student and professional retention, and (4)
      student maturity. The second higher-order theme, disadvantages, was defined by 3
      factors: (1) limited time for autonomous practice, (2) financial concerns, and
      (3) lack of evidence for the transition. CONCLUSIONS: Athletic training students,
      faculty, and preceptors demonstrated moderate support for a transition to the
      graduate-level model. Factors supporting the move were comparable with those
      detailed in a recent document on professional education in athletic training
      presented to the National Athletic Trainers' Association Board of Directors. The
      concerns about and reasons against a move have been discussed by those in the
      profession.

PMID- 26287490
TI  - Systematic Review and Meta-Analysis of the Epidemiology of Vancomycin
      Intermediate and Heterogeneous Vancomycin-Intermediate Staphylococcus aureus
      Isolates.
AB  - BACKGROUND: Vancomycin-intermediate Staphylococcus aureus (VISA) and
      heterogeneous VISA (hVISA) are associated with vancomycin treatment failure, and
      are becoming an increasing public health problem. Therefore, we undertook this
      study of 91 published studies and made subgroup comparisons of hVISA/VISA
      incidence in different study years, locations, and types of clinical samples. We
      also analyzed the genetic backgrounds of these strains. METHODS: A systematic
      literature review of relevant articles published in PubMed and EMBASE from
      January 1997 to August 2014 was conducted. We selected and assessed journal
      articles reporting the prevalence rates of hVISA/VISA. RESULTS: The pooled
      prevalence of hVISA was 6.05% in 99,042 methicillin-resistant S. aureus (MRSA)
      strains and that of VISA was 3.01% in 68,792 MRSA strains. The prevalence of
      hVISA was 4.68% before 2006, 5.38% in 2006-2009, and 7.01% in 2010-2014. VISA
      prevalence was 2.05%, 2.63%, and 7.93%, respectively. In a subgroup analysis of
      different isolation locations, the prevalence of hVISA strains was 6.81% in Asia
      and 5.60% in Europe/America, and that of VISA was 3.42% and 2.75%, respectively.
      The frequencies of hVISA isolated from blood culture samples and from all
      clinical samples were 9.81% and 4.68%, respectively, and those of VISA were 2.00%
      and 3.07%, respectively. The most prevalent genotype was staphylococcal cassette
      chromosome mec (SCCmec) II, which accounted for 48.16% and 37.74% of hVISA and
      VISA, respectively. Sequence Type (ST) 239 was most prevalent. CONCLUSION: The
      prevalence of hVISA/VISA has been increasing in recent years, but has been
      grossly underestimated. Its incidence is higher in Asia than in Europe/America.
      hVISA is isolated from blood culture samples more often than from other samples.
      These strains are highly prevalent in epidemic MRSA strains. This study clarifies
      the epidemiology of hVISA/VISA and indicates that the detection of these strains
      and the control of nosocomial infections must be strengthened.

PMID- 26287492
TI  - Preseason Perceived Physical Capability and Previous Injury.
AB  - CONTEXT: Patient opinion about the ability to perform athletic maneuvers is
      important after injury; however, prospective assessment of self-perceived
      physical capability for athletes before the beginning of a season is lacking.
      OBJECTIVE: To perform a descriptive analysis of knee, shoulder, and elbow self
      perceived measures of physical capability specific to athletics and to compare
      the measures between athletes with and without a history of injury. DESIGN: Cross
      sectional study. SETTING: Preparticipation physical examinations. PATIENTS OR
      OTHER PARTICIPANTS: A total of 738 collegiate athletes (486 men, 251 women; age =
      19 +/- 1 years) were administered questionnaires after receiving medical
      clearance to participate in their sports. Of those athletes, 350 reported a
      history of injury. MAIN OUTCOME MEASURE(S): Athletes self-reported a history of
      knee, shoulder, or elbow injury. Perceived physical capability of the 3 joints
      was evaluated using the Knee Injury and Osteoarthritis Outcome Score Sport and
      Recreation Function and Knee-Related Quality of Life subscales and the Kerlan
      Jobe Orthopaedic Clinic Shoulder and Elbow Score. We conducted nonparametric
      analysis to determine if scores differed between athletes with and without a
      history of injury. RESULTS: Median values for the Knee Injury and Osteoarthritis
      Outcome Score Sports and Recreation Function and Knee-Related Quality of Life
      subscales and the Kerlan-Jobe Orthopaedic Clinic Shoulder and Elbow Score for all
      athletes were 100. Median values for perceived physical capability of athletes
      with a history of injury were 3 to 12 points lower for each questionnaire before
      the start of the season (P < .001). CONCLUSIONS: Our study provided descriptive
      values for individual perceived knee, shoulder, and elbow physical capability of
      collegiate athletes participating in 19 sports. Athletes who did not report
      previous injuries perceived their physical capabilities to be nearly perfect,
      which could set the goal for these athletes to return to participation after
      injury. Athletes reporting previous injuries perceived less physical capability
      before the competitive season. Self-assessment of joint-specific capability may
      supplement preseason physical examinations, identifying particular athletes
      needing further monitoring or care during a season.

PMID- 26287493
TI  - Exploring the Athletic Trainer's Role in Assisting Student-Athletes Presenting
      With Alcohol-Related Unintentional Injuries.
AB  - Compared with their nonathlete peers, collegiate athletes consume higher
      quantities of alcohol, drink with greater frequency, and exhibit an increased
      propensity to engage in heavy episodic drinking (ie, binge drinking), which often
      may result in alcohol-related consequences. Moreover, collegiate athletes are
      also more likely to engage in other maladaptive lifestyle behaviors, such as
      participating in physical fights and riding with an intoxicated driver, and less
      likely to engage in protective behaviors, such as wearing a helmet while
      operating a motorcycle, moped, or bicycle. Taken together, these behaviors
      clearly pose a health risk for student-athletes and increase the likelihood that
      they will experience an alcohol-related unintentional injury (ARUI). An ARUI
      represents a risk not only to the health and well-being of collegiate athletes
      but also to their athletic performances, collegiate careers, and potential
      professional opportunities. Therefore, athletic trainers need to be equipped with
      the knowledge and skills to provide face-to-face brief interventions to student
      athletes presenting with ARUIs and to evaluate the effect of their involvement.
      We address potential action items for implementation by athletic trainers. 

PMID- 26287495
TI  - The Preinterventional Cystatin-Creatinine-Ratio: A Prognostic Marker for Contrast
      Medium-Induced Acute Kidney Injury and Long-Term All-Cause Mortality.
AB  - BACKGROUND/AIMS: Contrast medium-induced acute kidney injury (CI-AKI) is an
      important iatrogenic complication following the injection of iodinated contrast
      media. The level of serum creatinine (SCr) is the currently accepted 'gold
      standard' to diagnose CI-AKI. Cystatin C (CyC) has been detected as a more
      sensitive marker for renal dysfunction. Both have their limitations. METHODS: The
      role of the preinterventional CyC-SCr ratio for evaluating the risk for CI-AKI
      and long-term all-cause mortality was retrospectively analyzed in the prospective
      single-center 'Dialysis-versus-Diuresis trial'. CI-AKI was defined and staged
      according to the Acute Kidney Injury Network classification. RESULTS: Three
      hundred and seventy-three patients were included (average age 67.4 +/- 10.2
      years, 16.4% women, 29.2% with diabetes mellitus, mean baseline glomerular
      filtration rate 56.3 +/- 20.2 ml/min/1.73 m(2) [as estimated by Chronic Kidney
      Disease Epidemiology Collaboration Serum Creatinine Cystatin C equation], 5.1%
      ejection fraction <35%). A total of 79 patients (21.2%) developed CI-AKI after
      elective heart catheterization, and 65 patients (17.4%) died during follow-up.
      Multivariate analyses by logistic regression confirmed that the preinterventional
      CyC-SCr ratio is independently associated with CI-AKI (OR 9.423, 95% CI 1.494
      59.436, p = 0.017). Also, the Cox regression model found a high significant
      association between preinterventional CyC-SCr ratio and long-term all-cause
      mortality (mean follow-up 649 days, hazards ratio 4.096, 95% CI 1.625-10.329, p =
      0.003). CONCLUSION: The preinterventional CyC-SCr ratio is independently
      associated with CI-AKI and highly significant associated with long-term mortality
      after heart catheterization.

PMID- 26287496
TI  - Brain Uptake of Tetrahydrohyperforin and Potential Metabolites after Repeated
      Dosing in Mice.
AB  - Tetrahydrohyperforin (IDN-5706) is a semisynthetic derivative of hyperforin, one
      of the main active components of Hypericum perforatum extracts. It showed
      remarkable positive effects on memory and cognitive performances in wild-type
      mice and in a transgenic mouse model of Alzheimer's disease, but little was known
      about the concentrations it can reach in the brain. The investigations reported
      herein show that repeated treatment of mice with tetrahydrohyperforin (20 mg/kg
      intraperitoneally, twice daily for 4 days and once on the fifth day) results in
      measurable concentrations in the brain, up to 367 ng/g brain (~700 nM) 6 h after
      the last dose; these concentrations have significant effects on synaptic function
      in hippocampal slices. The other main finding was the identification and
      semiquantitative analysis of tetrahydrohyperforin metabolites. In plasma, three
      hydroxylated/dehydrogenated metabolites were the largest (M1-3) and were also
      formed in vitro on incubation of tetrahydrohyperforin with mouse liver
      microsomes; the fourth metabolite in abundance was a hydroxylated/deisopropylated
      derivative (M13), which was not predicted in vitro. These metabolites were all
      detected in the brain, with peak areas from 10% (M1) to ~1.5% (M2, M3, and M13)
      of the parent compound. In summary, repeated treatment of mice with
      tetrahydrohyperforin gave brain concentrations that might well underlie its
      central pharmacological effects. We also provide the first metabolic profile of
      this compound.

PMID- 26287494
TI  - 6-Formylindolo(3,2-b)Carbazole (FICZ) Modulates the Signalsome Responsible for RA
      Induced Differentiation of HL-60 Myeloblastic Leukemia Cells.
AB  - 6-Formylindolo(3,2-b)carbazole (FICZ) is a photoproduct of tryptophan and an
      endogenous high affinity ligand for aryl hydrocarbon receptor (AhR). It was
      previously reported that, in patient-derived HL-60 myeloblastic leukemia cells,
      retinoic acid (RA)-induced differentiation is driven by a signalsome containing c
      Cbl and AhR. FICZ enhances RA-induced differentiation, assessed by expression of
      the membrane differentiation markers CD38 and CD11b, cell cycle arrest and the
      functional differentiation marker, inducible oxidative metabolism. Moreover, FICZ
      augments the expression of a number of the members of the RA-induced signalsome,
      such as c-Cbl, Vav1, Slp76, PI3K, and the Src family kinases Fgr and Lyn.
      Pursuing the molecular signaling responsible for RA-induced differentiation, we
      characterized, using FRET and clustering analysis, associations of key molecules
      thought to drive differentiation. Here we report that, assayed by FRET, AhR
      interacts with c-Cbl upon FICZ plus RA-induced differentiation, whereas AhR
      constitutively interacts with Cbl-b. Moreover, correlation analysis based on the
      flow cytometric assessment of differentiation markers and western blot detection
      of signaling factors reveal that Cbl-b, p-p38alpha and pT390-GSK3beta, are not
      correlated with other known RA-induced signaling components or with a phenotypic
      outcome. We note that FICZ plus RA elicited signaling responses that were not
      typical of RA alone, but may represent alternative differentiation-driving
      pathways. In clusters of signaling molecules seminal to cell differentiation,
      FICZ co-administered with RA augments type and intensity of the dynamic changes
      induced by RA. Our data suggest relevance for FICZ in differentiation-induction
      therapy. The mechanism of action includes modulation of a SFK and MAPK centered
      signalsome and c-Cbl-AhR association. 

PMID- 26287497
TI  - A kiss is not a kiss: visually evoked neuromagnetic fields reveal differential
      sensitivities to brief presentations of kissing couples.
AB  - With a few exceptions, the literature on face recognition and its neural basis
      derives from the presentation of single faces. However, in many ecologically
      typical situations, we see more than one face, in different communicative
      contexts. One of the principal ways in which we interact using our faces is
      kissing. Although there is no obvious taxonomy of kissing, we kiss in various
      interpersonal situations (greeting, ceremony, sex), with different goals and
      partners. Here, we assess the visual cortical responses elicited by viewing
      different couples kissing with different intents. The study thus lies at the
      nexus of face recognition, action recognition, and social neuroscience.
      Magnetoencephalography data were recorded from nine participants in a passive
      viewing paradigm. We presented images of couples kissing, with the images
      differing along two dimensions, kiss type and couple type. We quantified event
      related field amplitudes and latencies. In each participant, the canonical
      sequence of event-related fields was observed, including an M100, an M170, and a
      later M400 response. The earliest two responses were significantly modulated in
      latency (M100) or amplitude (M170) by the sex composition of the images (with
      male-male and female-female pairings yielding faster latency M100 and larger
      amplitude M170 responses). In contrast, kiss type showed no modulation of any
      brain response. The early cortical-evoked fields that we typically associate with
      the presentation and analysis of single faces are differentially sensitive to
      complex social and action information in face pairs that are kissing. The early
      responses, typically associated with perceptual analysis, exhibit a consistent
      grouping and suggest a high and rapid sensitivity to the composition of the
      kissing pairs. 

PMID- 26287498
TI  - CXCL5 is associated with the increased risk of coronary artery disease.
AB  - OBJECTIVE: To investigate the relevant expression of CXCL5 and CXCR2 in human
      atherosclerotic coronary artery and to study the association between the CXCL5
      variant and coronary artery disease (CAD) in a Chinese Han population. MATERIALS
      AND METHODS: CXCL5 and CXCR2 expression in human coronary arteries was detected
      by immunohistochemical staining and western blotting analysis. The association
      between the CXCL5 variant and CAD was determined in a community-based sample by
      PCR-direct sequence analysis in a Chinese Han population. Finally, plasma CXCL5
      levels were measured in a case-control study of CAD patients. RESULTS: We found
      that CXCL5 and CXCR2 expressions were higher in atherosclerotic coronary arteries
      plaque than in the normal coronary arteries. CXCL5 and CXCR2 expression levels
      increased in line with coronary artery lesion stages. A functional nonsynonymous 
      156 G/C in the CXCL5 promoter region was associated with CAD and plasma CXCL5
      levels were significantly increased in CAD patients compared with control
      subjects (3891.21+/-1403.08 vs. 2812.39+/-840.62 pg/ml, P<0.05). Individuals with
      the CXCL5 promoter -156 G/C variant C/C and G/C carriers had higher plasma CXCL5
      levels than those with the G/G genotype carriers in both CAD patients and control
      participants. CONCLUSION: CXCL5 and CXCR2 are enriched in human atherosclerotic
      coronary artery. Our findings show that the CXCL5 variant might be a genetic risk
      factor for the susceptibility of CAD and the CXCL5 promoter -156 G/C C allele
      might be an independent predictor for CAD. CXCL5 may be a useful molecular marker
      and a possible target for the treatment of CAD.

PMID- 26287499
TI  - Visualizing phase transition behavior of dilute stimuli responsive polymer
      solutions via Mueller matrix polarimetry.
AB  - Probing volume phase transition behavior of superdiluted polymer solutions both
      micro- and macroscopically still persists as an outstanding challenge. In this
      regard, we have explored 4 * 4 spectral Mueller matrix measurement and its
      inverse analysis for excavating the microarchitectural facts about stimuli
      responsiveness of "smart" polymers. Phase separation behavior of thermoresponsive
      poly(N-isopropylacrylamide) (PNIPAM) and pH responsive poly(N,N
      (dimethylamino)ethyl methacrylate) (PDMAEMA) and their copolymers were analyzed
      in terms of Mueller matrix derived polarization parameters, namely,
      depolarization (Delta), diattenuation (d), and linear retardance (delta). The
      Delta, d, and delta parameters provided useful information on both macro- and
      microstructural alterations during the phase separation. Additionally, the two
      step action ((i) breakage of polymer-water hydrogen bonding and (ii) polymer
      polymer aggregation) at the molecular microenvironment during the cloud point
      generation was successfully probed via these parameters. It is demonstrated that,
      in comparison to the present techniques available for assessing the hydrophobic
      hydrophilic switch over of simple stimuli-responsive polymers, Mueller matrix
      polarimetry offers an important advantage requiring a few hundred times dilute
      polymer solution (0.01 mg/mL, 1.1-1.4 MUM) at a low-volume format. 

PMID- 26287500
TI  - What Makes the Photocatalytic CO2 Reduction on N-Doped Ta2O5 Efficient: Insights
      from Nonadiabatic Molecular Dynamics.
AB  - Recent experimental studies demonstrated that photocatalytic CO2 reduction by Ru
      catalysts assembled on N-doped Ta2O5 surface is strongly dependent on the nature
      of the anchor group with which the Ru complexes are attached to the substrate. We
      report a comprehensive atomistic analysis of electron transfer dynamics in
      electroneutral Ru(di-X-bpy) (CO)2Cl2 complexes with X = COOH and PO3H2 attached
      to the N-Ta2O5 substrate. Nonadiabatic molecular dynamics simulations indicate
      that the electron transfer is faster in complexes with COOH anchors than in
      complexes with PO3H2 groups, due to larger nonadiabatic coupling. Quantum
      coherence counteracts this effect, however, to a small extent. The COOH anchor
      promotes the transfer with significantly higher frequency modes than PO3H2, due
      to both lighter atoms (C vs P) and stronger bonds (double vs single). The
      acceptor state delocalizes onto COOH, but not PO3H2, further favoring electron
      transfer in the COOH system. At the same time, the COOH anchor is prone to
      decomposition, in contrast to PO3H2, making the former show smaller turnover
      numbers in some cases. These theoretical predictions are consistent with recent
      experimental results, legitimating the proposed mechanism of the electron
      transfer. We emphasize the role of anchor stability, nonadiabatic coupling, and
      quantum coherence in determining the overall efficiency of artificial
      photocatalytic systems. 

PMID- 26287501
TI  - MeOTf-Induced Carboannulation of Isothiocyanates and Aryl Alkynes with C?S Bond
      Cleavage: Access to Indenones.
AB  - MeOTf-induced carboannulation of alkyl isothiocyanates and aryl alkynes for the
      synthesis of indenones in good yields under metal-free conditions with C?S bond
      cleavage is described. The thioalkoxy group at the 3-position of the indenone can
      also be converted into other functional groups, such as phenyl, methylsulfonyl,
      amino, and ethoxy groups. 

PMID- 26287502
TI  - Racemic total synthesis of dactyloidin and demethyldactyloidin through the DL
      proline-catalyzed Knoevenagel condensation/[4 + 2] cycloaddition cascade.
AB  - An efficient approach towards the first racemic total synthesis of dactyloidin
      (2) and demethyldactyloidin (3) is described. Their oxygen-bridged tricyclic
      ketal systems were rapidly constructed by using a remarkable biomimetic
      Knoevenagel condensation/[4 + 2] cycloaddition cascade as the critical strategy
      and the 1,5-dicarbonyl segment was assembled by Grignard addition.

PMID- 26287503
TI  - Facility-based treatment for medical complications resulting from unsafe
      pregnancy termination in the developing world, 2012: a review of evidence from 26
      countries.
AB  - With changing conditions affecting receipt of postabortion care, an updated
      estimate of the incidence of treatment for complications from unsafe pregnancy
      termination is needed to inform policies and programmes. National estimates of
      facility-based treatment for complications in 26 countries form the basis for
      estimating treatment rates in the developing world. An estimated seven million
      women were treated in the developing world for complications from unsafe
      pregnancy termination in 2012, a rate of 6.9 per 1000 women aged 15-44 years.
      Regionally, rates ranged from 5.3 in Latin America and the Caribbean to 8.2 in
      Asia. Results inform policies to improve women's health. TWEETABLE ABSTRACT: An
      estimated 7 million women were treated in the developing world for complications
      of unsafe TOP in 2012.

PMID- 26287504
TI  - MicroRNA-150: A potential regulator in pathogens infection and autoimmune
      diseases.
AB  - MicroRNAs (miRNAs) are short non-coding RNAs that play an important role in post
      transcriptional regulation of gene expression. The past studies showed that miR
      150 might emerge as a master regulator of gene expression during the immune cells
      differentiation and immune response process. Its regulation ability in immune
      cellular process might contribute to the host defense against invading pathogens,
      and dysregulated expression of miR-150 in immune cells might result in autoimmune
      diseases. This review summarized that miR-150 could regulate B cells, T cells and
      NK/iNKT cells differentiation and immune response. And also, this review provides
      a comprehensive view on the association of miR-150 and autoimmune diseases such
      as systemic sclerosis (SSc), multiple sclerosis, rheumatoid arthritis, systemic
      lupus erythematosus and contact sensitivity. Especially, the duplex role of miR
      150 in the fibrosis process might contribute to the pathomechanism of SSc. Though
      much remains to be explored about the roles of miR-150 in pathogenic infection
      and autoimmune diseases, targeting miR-150 may serve as a promising therapy
      strategy. 

PMID- 26287505
TI  - Enhanced Cytoplasmic Delivery of RAGE siRNA Using Bioreducible Polyethylenimine
      based Nanocarriers for Myocardial Gene Therapy.
AB  - This study aims to develop bioreducible polyethylenimine (rPEI)/siRNA polyplexes
      with high stability, high transfection efficiency, and low cytotoxicity for
      efficient cytoplasmic siRNA delivery. rPEI successfully incorporated siRNA into
      stable and compact nanocomplexes, and the disulfide linkages in rPEI/siRNA were
      cleaved under reductive environments, resulting in efficient intracellular
      translocation and siRNA release. In this study, receptor for advanced glycation
      end-products (RAGE) was selected as a therapeutic target gene because it is
      associated with inflammatory responses in ischemia/reperfusion injury.
      rPEI/siRAGE exhibited high target gene silencing and low cytotoxicity in
      cardiomyocytes, and the treatment of rPEI/siRAGE reduced the myocardial
      infarction size. 

PMID- 26287506
TI  - Association between medical home enrollment and health care utilization and costs
      among breast cancer patients in a state Medicaid program.
AB  - BACKGROUND: The patient-centered medical home (PCMH) is increasingly being
      implemented in an effort to improve and coordinate primary care, but its effect
      on health care utilization among breast cancer patients remains unclear. The
      objective of this study was to examine health care utilization and expenditures
      as a function of PCMH enrollment among breast cancer patients in North Carolina's
      Medicaid program. METHODS: North Carolina Medicaid claims linked to North
      Carolina Central Cancer Registry records (2003-2007) were used to examine monthly
      patterns of health care use and expenditures. Controlling for a selection bias
      for time-invariant characteristics, fixed effects regression models analyzed
      associations between PCMH enrollment and utilization of outpatient, inpatient,
      and emergency department (ED) services and Medicaid expenditures during the 15
      months after the diagnosis of breast cancer. RESULTS: Among 758 breast cancer
      patients, 381 (50%) were enrolled in a PCMH at some time in the 15 months after
      diagnosis. After controlling for individual fixed effects, PCMH enrollment was
      significantly associated with greater outpatient service use, but there was no
      difference in the probability of inpatient hospitalizations or ED visits.
      Enrollment in a PCMH was associated with increased average expenditures of $429
      per month during the first 15 months. CONCLUSIONS: Greater outpatient care
      utilization and increased average expenditures among breast cancer patients
      enrolled in a PCMH may suggest that these women have improved access to primary
      and specialty care. Expanding PCMHs may change patterns of service utilization
      for Medicaid breast cancer patients but may not be associated with lower costs.

PMID- 26287507
TI  - Pandemic influenza virus, pH1N1, induces asthmatic symptoms via activation of
      innate lymphoid cells.
AB  - BACKGROUND: The pandemic strain of the influenza A virus (pH1N1) in 2009 caused
      many complications in patients. In this study, we introduce asthmatic symptoms as
      a complication of pH1N1 infection in children, not having a relationship with
      asthma history. The aim of this study was to quantify asthmatic symptoms in pH1N1
      infected children and elucidate the underlying mechanisms of airway hyper
      responsiveness (AHR) induced in a murine model of pH1N1 infection. METHODS: As a
      retrospective study, pH1N1-infected children who were hospitalized with moderate
      to severe acute asthmatic symptoms were enrolled and administered a methacholine
      challenge test (MCT) at 3 months post-discharge. Additionally, the induction of
      AHR by pH1N1 infection was measured by MCT in wild-type and Rag1(-/-) mice. The
      effect of the innate immune response on the development of AHR following pH1N1
      infection was investigated. RESULTS: More than 70% of the pH1N1-infected children
      without a pre-infection diagnosis of asthma had a negative response on the MCT.
      None of these children had recurrent wheezing or asthma during the 3 years
      following pH1N1 infection. The development of AHR in pH1N1-infected mice was
      associated with an elevation in IL-33 and innate lymphoid cells 2 (ILC2).
      CONCLUSIONS: This study demonstrates that pH1N1 infection directly induces
      transient asthmatic symptoms in patients regardless of their medical history.
      pH1N1 infection was shown to stimulate the rapid development of AHR and Th2-type
      cytokine secretion in mice via the activation of ILC2; it may be activated
      independently of adaptive immunity.

PMID- 26287508
TI  - Ultralow Loading of Silver Nanoparticles on Mn2O3 Nanowires Derived with Molten
      Salts: A High-Efficiency Catalyst for the Oxidative Removal of Toluene.
AB  - Using a mixture of NaNO3 and NaF as molten salt and MnSO4 and AgNO3 as metal
      precursors, 0.13 wt % Ag/Mn2O3 nanowires (0.13Ag/Mn2O3-ms) were fabricated after
      calcination at 420  degrees C for 2 h. Compared to the counterparts derived via
      the impregnation and poly(vinyl alcohol)-protected reduction routes as well as
      the bulk Mn2O3-supported silver catalyst, 0.13Ag/Mn2O3-ms exhibited a much higher
      catalytic activity for toluene oxidation. At a toluene/oxygen molar ratio of
      1/400 and a space velocity of 40,000 mL/(g h), toluene could be completely
      oxidized into CO2 and H2O at 220  degrees C over the 0.13Ag/Mn2O3-ms catalyst.
      Furthermore, the toluene consumption rate per gram of noble metal over
      0.13Ag/Mn2O3-ms was dozens of times as high as that over the supported Au or AuPd
      alloy catalysts reported in our previous works. It is concluded that the
      excellent catalytic activity of 0.13Ag/Mn2O3-ms was associated with its high
      dispersion of silver nanoparticles on the surface of Mn2O3 nanowires and good low
      temperature reducibility. Due to high efficiency, good stability, low cost, and
      convenient preparation, 0.13Ag/Mn2O3-ms is a promising catalyst for the practical
      removal of volatile organic compounds.

PMID- 26287509
TI  - Impaired reward processing in the human prefrontal cortex distinguishes between
      persistent and remittent attention deficit hyperactivity disorder.
AB  - Symptoms of attention deficit hyperactivity disorder (ADHD) in children often
      persist into adulthood and can lead to severe antisocial behavior. However, to
      date it remains unclear whether neuro-functional abnormalities cause ADHD, which
      in turn can then provide a marker of persistent ADHD. Using event-related
      functional magnetic resonance imaging (fMRI), we measured blood oxygenation level
      dependent (BOLD) signal changes in subjects during a reversal learning task in
      which choice of the correct stimulus led to a probabilistically determined
      'monetary' reward or punishment. Participants were diagnosed with ADHD during
      their childhood (N=32) and were paired with age, gender, and education matched
      healthy controls (N=32). Reassessment of the ADHD group as adults resulted in a
      split between either persistent (persisters, N=17) or remitted ADHDs (remitters,
      N=15). All three groups showed significantly decreased activation in the medial
      prefrontal cortex (PFC) and the left striatum during punished correct responses,
      however only remitters and controls presented significant psycho-physiological
      interaction between these fronto-striatal reward and outcome valence networks.
      Comparing persisters to remitters and controls showed significantly inverted
      responses to punishment (P<0.05, family-wise error corrected) in left PFC region.
      Interestingly, the decreased activation shown after punishment was located in
      different areas of the PFC for remitters compared with controls, suggesting that
      remitters might have learned compensation strategies to overcome their ADHD
      symptoms. Thus, fMRI helps understanding the neuro-functional basis of ADHD
      related behavior differences and differentiates between persistent and remittent
      ADHD.

PMID- 26287510
TI  - Unique Dual Functions for Carbon Dots in Emulsion Preparations: Costabilization
      and Fluorescence Probing.
AB  - Recently, carbon dots (CDs) have drawn much attention as evidenced by their
      incorporation into many branches of science and engineering. Herein, a further
      unique application is elucidated: CDs that are synthesized by the hydrothermal
      treatment of gelatin for a dual functionality as expressed in costabilization of
      particle-based emulsions and their concomitant role as fluorescent probes. CDs
      either with or without gelatin matrixes induce the aggregation of Laponite
      particles. The introduction of CDs thus enhanced the stability of Laponite
      stabilized emulsions and promoted the formation of multiple emulsions and
      emulsions with fine and uniform droplets when the CD-to-Laponite mass ratio was
      less than 45% and exceeded 60%, respectively. However, CDs without gelatin
      matrixes show slightly higher efficiency than CDs within gelatin matrixes for the
      costabilization of emulsions. CDs also costabilized emulsions with Laponite to
      allow the distribution of Laponite particles to be traced and the emulsion
      profiled under UV. 

PMID- 26287511
TI  - How to assess diabetes distress: comparison of the Problem Areas in Diabetes
      Scale (PAID) and the Diabetes Distress Scale (DDS).
AB  - AIMS: To compare the properties of the two most commonly used assessment tools
      for diabetes distress, the Problem Areas in Diabetes Scale (PAID) and the
      Diabetes Distress Scale (DDS), in order to discriminate their psychometric
      capabilities and functions. METHODS: Six hundred and twenty-eight people with
      diabetes (67% Type 1, 33% Type 2) were cross-sectionally assessed with the PAID,
      the DDS and further self-report scales regarding coping, quality of life,
      depressive symptoms and self-care, and medical data were gained. We analysed the
      PAID and DDS for areas of contentual/psychometric divergence in assessing
      diabetes distress and compared their associations with criteria of interest.
      RESULTS: Content analysis: The PAID covers a greater variety of emotional
      concerns and shows a stronger focus on food-related problems and complications.
      The DDS is more reflective of physician-related distress and problems concerning
      diabetes self-management. Psychometric analysis: Exploratory factor analyses
      revealed four-factor structures of both scales, explaining 60% (PAID) and 67%
      (DDS) of variance. Confirmatory factor analyses confirmed that single-factor and
      four-factor models fit the data. Total scales proved high and subscales mostly
      satisfactory reliability. Associations with criteria of interest: The PAID was
      significantly more strongly associated with dysfunctional coping styles, quality
      of life and depressive symptoms. The DDS showed significantly stronger
      associations with diabetes self-care and metabolic outcomes. CONCLUSION: Our
      results support both PAID and DDS as good self-report measures of diabetes
      distress. The observed contentual/psychometric differences suggest that a
      justified choice with regard to the intended clinical or scientific purpose can
      improve the acquisition of the required data.

PMID- 26287512
TI  - Synthesis of Tolmetin Hydrazide-Hydrazones and Discovery of a Potent Apoptosis
      Inducer in Colon Cancer Cells.
AB  - Tolmetin hydrazide and a novel series of tolmetin hydrazide-hydrazones 4a-l were
      synthesized in this study. The structures of the new compounds were determined by
      spectral (FT-IR, (1)H NMR) methods. N'-[(2,6-Dichlorophenyl)methylidene]-2-[1
      methyl-5-(4-methylbenzoyl)-1H-pyrrol-2-yl]acetohydrazide (4g) was evaluated in
      vitro using the MTT colorimetric method against the colon cancer cell lines HCT
      116 (ATCC, CCL-247) and HT-29 (ATCC, HTB-38) to determine growth inhibition and
      cell viability at different doses. Compound 4g exhibited anti-cancer activity
      with an IC50 value of 76 MUM against colon cancer line HT-29 (ATCC, HTB-38) and
      did not display cytotoxicity toward control NIH3T3 mouse embryonic fibroblast
      cells compared to tolmetin. In addition, this compound was evaluated for caspase
      3, caspase-8, caspase-9, and annexin-V activation in the apoptotic pathway, which
      plays a key role in the treatment of cancer. We demonstrated that the anti-cancer
      activity of this compound was due to the activation of caspase-8 and caspase-9
      involved in the apoptotic pathway. In addition, in this study, we investigated
      the catalytical effect of COX on the HT-29 cancer line, the apoptotic mechanism,
      and the moleculer binding of tolmetin and compound 4g on the COX enzyme active
      site.

PMID- 26287513
TI  - Dual-Phase Glass Ceramic: Structure, Dual-Modal Luminescence, and Temperature
      Sensing Behaviors.
AB  - Yb(3+)/Er(3+)/Cr(3+) triply doped transparent bulk glass ceramic containing
      orthorhombic YF3 and cubic Ga2O3 nanocrystals was fabricated by a melt-quenching
      route to explore its possible application in optical thermometry with high
      spatial and temperature resolution. It was experimentally observed that
      Yb(3+)/Er(3+) ions incorporated into the precipitated YF3 nanophase, while Cr(3+)
      ions partitioned into the crystallized Ga2O3 nanophase after glass
      crystallization. Importantly, such spatial isolation strategy efficiently
      suppressed adverse energy transfer among different active ions. As a consequence,
      intense green anti-Stokes luminescence originated from Er(3+): (2)H11/2,(4)S3/2 
      > (4)I15/2 transitions, and deep-red Stokes luminescence transitions assigned to
      Cr(3+): (2)E -> (4)A2 radiation were simultaneously realized. Impressively, the
      intermediate crystal-field environment for Cr(3+) in Ga2O3 made it possible for
      lifetime-based temperature sensing owing to the competition of radiation
      transitions from the thermally coupled Cr(3+) (2)E and (4)T2 excited states. In
      the meantime, the low-phonon-energy environment for Er(3+) in YF3 was beneficial
      for upconversion fluorescence intensity ratio-based temperature sensing via
      thermal population between the (2)H11/2 state and (4)S3/2 state. The Boltzmann
      distribution theory and the two-level kinetic model were adopted to interpret
      these temperature-dependent luminescence of Er(3+) and Cr(3+), respectively,
      which gave the highest temperature sensitivities of 0.25% K(-1) at 514 K for
      Er(3+) and 0.59% K(-1) at 386 K for Cr(3+). 

PMID- 26287514
TI  - Augmentation of Lysosomal Phospholipase A2 Activity in the Anterior Chamber in
      Glaucoma.
AB  - AIM: The lysosomal enzyme in the anterior chamber has a crucial role in the
      digestion of the insoluble materials in the aqueous humor (AH). The dysfunction
      of AH filtration in the trabecular meshwork (TM) causes increasing AH outflow
      resistance in the TM. Those insoluble objects, including phospholipids, should be
      digested in the TM for normal outflow. The present study was conducted to explore
      the involvement of lysosomal phospholipase A2 (LPLA2), a phospholipid-degrading
      enzyme, of the AH in glaucoma using clinical AH specimens. MATERIALS AND METHODS:
      One hundred and twenty-five AH specimens were collected from patients. The
      measurement of LPLA2 activity in the AH was carried out using liposomes
      consisting of phosphatidylglycerol and N-acetylsphingosine (NAS). The correlation
      between the LPLA2 activity in the AH and ocular diseases was investigated.
      RESULTS: The human AH showed both transacylation of NAS and the release of fatty
      acids under acidic conditions but not at a neutral pH, which is consistent with
      the known properties of LPLA2. The LPLA2 activity in the AH was not affected by
      age or systemic disease. A comparison between ocular diseases showed that the AH
      specimens obtained from patients with glaucoma had significantly higher LPLA2
      activity than the other ocular disease groups. DISCUSSION: The present findings
      suggest that the ascended level of LPLA2 activity in the AH of glaucoma patients
      is associated with the development of glaucoma.

PMID- 26287515
TI  - Change and Stability in Religiousness and Spirituality in Emerging Adulthood.
AB  - The author investigated the change and stability of different aspects of
      religiousness and spirituality, as well as whether personality traits may help
      explain why individuals increase or decrease in religiousness and spirituality
      during emerging adulthood. Self-report measures of childhood and current
      religiousness were completed by 224 college-aged participants. A subset of
      participants also completed a measure of personality and measures of religious
      and spiritual belief trajectories by rating the importance of each belief at
      successive age brackets across their lifespan. Analyses of mean-level, rank
      order, and individual-level stability and change in religiousness indicated that
      while average religiousness scores decreased, there was still moderate to high
      rank-order stability in scores. Additionally, service attendance was less stable
      and decreased more than importance of religion in daily life. Examination of the
      trajectories of religiousness and spirituality over time showed similar
      differences: religiousness decreased, on average, whereas spirituality increased
      slightly, but significantly, across successive age brackets. Personality traits
      did not significantly predict change in religiousness over time, although
      openness predicted change in spirituality. Conclusions include the idea that
      religiousness in emerging adulthood is comprised on different components that
      change at different rates. 

PMID- 26287517
TI  - Spontaneous emergence of chirality in achiral lyotropic chromonic liquid crystals
      confined to cylinders.
AB  - The presumed ground state of a nematic fluid confined in a cylindrical geometry
      with planar anchoring corresponds to that of an axial configuration, wherein the
      director, free of deformations, is along the long axis of the cylinder. However,
      upon confinement of lyotropic chromonic liquid crystals in cylindrical
      geometries, here we uncover a surprising ground state corresponding to a doubly
      twisted director configuration. The stability of this ground state, which
      involves significant director deformations, can be rationalized by the saddle
      splay contribution to the free energy. We show that sufficient anisotropy in the
      elastic constants drives the transition from a deformation-free ground state to a
      doubly twisted structure, and results in spontaneous symmetry breaking with equal
      probability for either handedness. Enabled by the twist angle measurements of the
      spontaneous twist, we determine the saddle-splay elastic constant for chromonic
      liquid crystals for the first time. 

PMID- 26287519
TI  - Kinetics and mechanisms of reactions between H2O2 and copper and copper oxides.
AB  - One of the main challenges for the nuclear power industry today is the disposal
      of spent nuclear fuel. One of the most developed methods for its long term
      storage is the Swedish KBS-3 concept where the spent fuel is sealed inside copper
      canisters and placed 500 meters down in the bedrock. Gamma radiation will
      penetrate the canisters and be absorbed by groundwater thereby creating oxidative
      radiolysis products such as hydrogen peroxide (H2O2) and hydroxyl radicals (HO).
      Both H2O2 and HO are able to initiate corrosion of the copper canisters. In this
      work the kinetics and mechanism of reactions between the stable radiolysis
      product, H2O2, and copper and copper oxides were studied. Also the dissolution of
      copper into solution after reaction with H2O2 was monitored by ICP-OES. The
      experiments show that both H2O2 and HO are present in the systems with copper and
      copper oxides. Nevertheless, these species do not appear to influence the
      dissolution of copper to the same extent as observed in recent studies in
      irradiated systems. This strongly suggests that aqueous radiolysis can only
      account for a very minor part of the observed radiation induced corrosion of
      copper. 

PMID- 26287518
TI  - Sirtuin1 Suppresses Osteoclastogenesis by Deacetylating FoxOs.
AB  - Activation of Sirtuin1 (Sirt1), an nicotinamide adenine dinucleotide oxidized
      dependent deacetylase, by natural or synthetic compounds like resveratrol,
      SRT2104, or SRT3025 attenuates the loss of bone mass caused by ovariectomy,
      aging, or unloading in mice. Conversely, Sirt1 deletion in osteoclast progenitors
      increases osteoclast number and bone resorption. Sirt1 deacetylates forkhead box
      protein (Fox) O1, FoxO3, and FoxO4, and thereby modulates their activity. FoxOs
      restrain osteoclastogenesis and bone resorption. Here, we tested the hypothesis
      that the antiresorptive effects of Sirt1 are mediated by FoxOs. We report that
      Sirt1 activation by SRT2104 and SRT3025 inhibited murine osteoclast progenitor
      proliferation and reduced osteoclastogenesis. The effect of Sirt1 stimulators on
      osteoclastogenesis was abrogated in cells lacking FoxO1, FoxO3, and FoxO4. FoxO1
      acetylation was increased by knocking down Sirt1 or addition of receptor
      activator of nuclear factor kappa-B ligand, the critical cytokine for osteoclast
      differentiation. Furthermore, acetylation inhibited, whereas deacetylation
      promoted, FoxO-mediated transcription. SRT3025 increased the expression of the
      FoxO-target genes catalase and hemeoxygenase-1 (HO-1) in osteoclast progenitors,
      in a FoxO-dependent manner. HO-1 catabolizes heme and attenuates mitochondrial
      oxidative phosphorylation and ATP production in macrophages. HO-1 levels were
      strongly reduced and ATP levels increased by Receptor activator of nuclear factor
      kappa-B ligand. In contrast, SRT3025 and FoxOs decreased ATP production, and the
      effect of SRT3025 was mediated by FoxOs. These findings reveal that the
      antiosteoclastogenic actions of Sirt1 are mediated by FoxOs and result from
      impaired mitochondria activity. Along with earlier findings that the
      osteoblastogenic effects of Sirt1 are also mediated by FoxOs, these results
      establish that the dual antiosteoporotic efficacy of Sirt1 stimulators (ie,
      decreasing bone resorption and promoting bone formation) is mediated via FoxO
      deacetylation. 

PMID- 26287520
TI  - Evaluating Perioperative Outcomes and Efficiency Following Total Joint
      Arthroplasty in the United States and Canada.

PMID- 26287521
TI  - Selectively enhanced red upconversion luminescence and phase/size manipulation
      via Fe(3+) doping in NaYF4:Yb,Er nanocrystals.
AB  - Red upconversion luminescence (UCL) is selectively enhanced by about 7 times via
      Fe(3+) codoping into a NaYF4:Yb,Er nanocrystalline lattice. The maximum red-to
      green ratio (R/G) as well as the overall integrated UCL intensity features at an
      Fe(3+) content of 20 mol%. The size and phase of nanocrystals are simultaneously
      manipulated via Fe(3+) doping with various concentrations by a facile
      hydrothermal method. Contrary to the literature, the pure hexagonal phase appears
      when Fe(3+) concentrations are from 5 to 20 mol%, meanwhile, the size of
      NaYF4:Yb,Er nanocrystals reaches its maximum at 10 mol%. The intensified visible
      UCL especially the dominant red emission is mainly ascribed to the energy
      transfer (ET) from |(2)F7/2, (4)T1g > (Yb(3+)-Fe(3+) dimer) to (4)F9/2 (Er(3+))
      states as well as the distortion of the crystalline field symmetry upon Fe(3+)
      codoping. Dynamic investigation of (4)S3/2 and (4)F9/2 states under the pulsed
      laser excitation of 980 nm along with the diffuse reflectance data further
      supports the proposed mechanism of UC processes. The results show the remarkable
      promise of Fe(3+)-codoped NaYF4:Yb,Er nanocrystals as upconverting nanoprobes
      with high sensitivity and penetrability in deeper tissue for multimodal
      biomedical imaging. 

PMID- 26287522
TI  - Estimating Mortality Associated With Antipsychotics and Other Psychotropics-
      Reply.

PMID- 26287524
TI  - Stressing about misplaced fat is a key to longevity.
AB  - The abnormal accumulation of fat increases the lifespans of nematodes that lack
      sex cells. 

PMID- 26287523
TI  - Estrogen receptor beta gene polymorphisms and risk of recurrent pregnancy loss: a
      case-control study.
AB  - Estrogen might play a key role in the maintenance of pregnancy. We investigated
      the role of the ER-beta gene +1730 G/A, +1082 G/A, and CA repeat polymorphisms in
      Korean patients with recurrent pregnancy loss (RPL). Genotyping was performed
      using the TaqMan assay in 305 patients with at least two unexplained consecutive
      spontaneous miscarriages before 20 weeks of gestation and 299 controls. The
      genotype distributions of the ER-beta gene +1082 G/A and +1730 G/A polymorphisms
      in the RPL group did not differ from those in the control group. When the
      analysis was restricted to patients with three or more consecutive spontaneous
      miscarriages, there were also no differences in the genotype distribution between
      this subgroup and controls. The number of CA repeats was distributed from 13 to
      28 with two large peaks at 18 and 23 in patients with RPL and controls. Using the
      two major peaks as cut-offs, the allele distributions were compared between
      patients and controls. However, the distribution of ER-beta gene CA repeats did
      not differ between women with recurrent miscarriage and controls. Findings of the
      current study suggest that the ER-beta gene polymorphisms are not major
      determinants of the development of RPL in Korean women. 

PMID- 26287525
TI  - Registered report: Wnt activity defines colon cancer stem cells and is regulated
      by the microenvironment.
AB  - The Reproducibility Project: Cancer Biology seeks to address growing concerns
      about reproducibility in scientific research by replicating selected results from
      a substantial number of high-profile papers in the field of cancer biology. The
      papers, which were published between 2010 and 2012, were selected on the basis of
      citations and Altmetric scores (Errington et al., 2014). This Registered report
      describes the proposed replication plan of key experiments from 'Wnt activity
      defines colon cancer stem cells and is regulated by the microenvironment' by
      Vermeulen and colleagues, published in Nature Cell Biology in 2010 (Vermeulen et
      al., 2010). The key experiments that will be replicated are those reported in
      Figures 2F, 6D, and 7E. In these experiments, Vermeulen and colleagues utilize a
      reporter for Wnt activity and show that colon cancer cells with high levels of
      Wnt activity also express cancer stem cell markers (Figure 2F; Vermeulen et al.,
      2010). Additionally, treatment either with conditioned medium derived from
      myofibroblasts or with hepatocyte growth factor restored clonogenic potential in
      low Wnt activity colon cancer cells in vitro (Figure 6D; Vermeulen et al., 2010)
      and in vivo (Figure 7E; Vermeulen et al., 2010). The Reproducibility Project:
      Cancer Biology is a collaboration between the Center for Open Science and Science
      Exchange and the results of the replications will be published in eLife. 

PMID- 26287526
TI  - Enhanced cellular uptake of nanoparticles by increasing the hydrophobicity of
      poly(lactic acid) through copolymerization with cell-membrane-lipid components.
AB  - The influence of hydrophobicity on the internalization of polymeric nanoparticles
      (NPs) remains poorly investigated. The hydrophobicity of poly(L-lactide) was
      increased by copolymerization with cell-membrane-lipid components, and this
      significantly enhanced the uptake of NPs up to 60% in the human cervical cancer
      cell line in comparison to unmodified poly(L-lactide) NPs.

PMID- 26287528
TI  - So Close to a Deal: Spatial-Distance Cues Influence Economic Decision-Making in a
      Social Context.
AB  - Social distance (i.e., the degree of closeness to another person) affects the way
      humans perceive and respond to fairness during financial negotiations. Feeling
      close to someone enhances the acceptance of monetary offers. Here, we explored
      whether this effect also extends to the spatial domain. Specifically, using an
      iterated version of the Ultimatum Game in a within-subject design, we
      investigated whether different visual spatial distance-cues result in different
      rates of acceptance of otherwise identical monetary offers. Study 1 found that
      participants accepted significantly more offers when they were cued with spatial
      closeness than when they were cued with spatial distance. Study 2 replicated this
      effect using identical procedures but different spatial-distance cues in an
      independent sample. Importantly, our results could not be explained by feelings
      of social closeness. Our results demonstrate that mere perceptions of spatial
      closeness produce analogous-but independent-effects to those of social closeness.

PMID- 26287529
TI  - Probiotic Lactic Acid Bacteria and Skin Health.
AB  - Human skin is the first defense barrier against the external environment,
      especially microbial pathogens and physical stimulation. Many studies on skin
      health with Lactic acid bacteria (LAB) have been published for many years,
      including prevention of skin disease and improvement of skin conditions. LAB, a
      major group of gram-positive bacteria, are known to be beneficial to human health
      by acting as probiotics. Recent studies have shown that LAB and their extracts
      have beneficial effects on maintenance and improvement of skin health. Oral
      administration of Lactobacillus delbrueckii inhibits the development of atopic
      disease. In addition, LAB and LAB extracts are known to have beneficial effects
      on intestinal diseases, with Lactobacillus plantarum having been shown to
      attenuate IL-10 deficient colitis. In addition to intestinal health, L. plantarum
      also has beneficial effects on skin. pLTA, which is lipoteichoic acid isolated
      from L. plantarum, has anti-photoaging effects on human skin cells by regulating
      the expression matrix meralloprotionase-1 (MMP-1) expression. While several
      studies have proposed a relationship between diseases of the skin and small
      intestines, there are currently no published reviews of the effects of LAB for
      skin health through regulation of intestinal conditions and the immune system. In
      this review, we discuss recent findings on the effects of LAB on skin health and
      its potential applications in beauty foods. 

PMID- 26287527
TI  - Potential Biomarkers for Radiation-Induced Renal Toxicity following 177Lu
      Octreotate Administration in Mice.
AB  - The kidneys are one of the main dose-limiting organs in peptide receptor
      radionuclide therapy and due to large inter-individual variations in renal
      toxicity, biomarkers are urgently needed in order to optimize therapy and reduce
      renal tissue damage. The aim of this study was to investigate the
      transcriptional, functional, and morphological effects on renal tissue after
      177Lu-octreotate administration in normal mice, and to identify biomarkers for
      radiation induced renal toxicity. METHODS: C57BL/6N mice were i.v. injected with
      0, 30, 60, 90, 120, or 150 MBq 177Lu-octreotate (0, 16, 29, 40, 48, and 54 Gy to
      the kidneys). At 4, 8, and 12 months after administration, radiation-induced
      effects were evaluated in relation to (a) global transcriptional variations in
      kidney tissues, (b) morphological changes in the kidneys, (c) changes in white
      and red blood cell count as well as blood levels of urea, and (d) changes in
      renal function using 99mTc-DTPA/99mTc-DMSA scintigraphy. RESULTS: In general, the
      highest number of differentially regulated transcripts was observed at 12 months
      after administration. The Cdkn1a, C3, Dbp, Lcn2, and Per2 genes displayed a
      distinct dose-dependent regulation, with increased expression level with
      increasing absorbed dose. Ifng, Tnf, and Il1B were identified as primary up
      stream regulators of the recurrently regulated transcripts. Furthermore,
      previously proposed biomarkers for kidney injury and radiation damage were also
      observed. The functional investigation revealed reduced excretion of 99mTc-DTPA
      after 150 MBq, an increased uptake of 99mTc-DMSA at all dose levels compared with
      the controls, and markedly increased urea level in blood after 150 MBq at 12
      months. CONCLUSION: Distinct dose-response relationships were found for several
      of the regulated transcripts. The Cdkn1a, Dbp, Lcn2, and Per2 genes are proposed
      as biomarkers for 177Lu-octreotate exposure of kidney. Correlations to functional
      and morphological effects further confirm applicability of these genes as markers
      of radiation damage in kidney tissue.

PMID- 26287530
TI  - Testing Propositions Derived from Twitter Studies: Generalization and Replication
      in Computational Social Science.
AB  - Replication is an essential requirement for scientific discovery. The current
      study aims to generalize and replicate 10 propositions made in previous Twitter
      studies using a representative dataset. Our findings suggest 6 out of 10
      propositions could not be replicated due to the variations of data collection,
      analytic strategies employed, and inconsistent measurements. The study's
      contributions are twofold: First, it systematically summarized and assessed some
      important claims in the field, which can inform future studies. Second, it
      proposed a feasible approach to generating a random sample of Twitter users and
      its associated ego networks, which might serve as a solution for answering social
      scientific questions at the individual level without accessing the complete data
      archive. 

PMID- 26287531
TI  - Inactivated Enterovirus 71 Vaccine Produced by 200-L Scale Serum-Free
      Microcarrier Bioreactor System Provides Cross-Protective Efficacy in Human SCARB2
      Transgenic Mouse.
AB  - Epidemics and outbreaks caused by infections of several subgenotypes of EV71 and
      other serotypes of coxsackie A viruses have raised serious public health concerns
      in the Asia-Pacific region. These concerns highlight the urgent need to develop a
      scalable manufacturing platform for producing an effective and sufficient
      quantity of vaccines against deadly enteroviruses. In this report, we present a
      platform for the large-scale production of a vaccine based on the inactivated
      EV71(E59-B4) virus. The viruses were produced in Vero cells in a 200 L bioreactor
      with serum-free medium, and the viral titer reached 10(7) TCID50/mL 10 days after
      infection when using an MOI of 10(-4). The EV71 virus particles were harvested
      and purified by sucrose density gradient centrifugation. Fractions containing
      viral particles were pooled based on ELISA and SDS-PAGE. TEM was used to
      characterize the morphologies of the viral particles. To evaluate the cross
      protective efficacy of the EV71 vaccine, the pooled antigens were combined with
      squalene-based adjuvant (AddaVAX) or aluminum phosphate (AlPO4) and tested in
      human SCARB2 transgenic (Tg) mice. The Tg mice immunized with either the AddaVAX-
      or AlPO4-adjuvanted EV71 vaccine were fully protected from challenges by the
      subgenotype C2 and C4 viruses, and surviving animals did not show any degree of
      neurological paralysis symptoms or muscle damage. Vaccine treatments
      significantly reduced virus antigen presented in the central nervous system of Tg
      mice and alleviated the virus-associated inflammatory response. These results
      strongly suggest that this preparation results in an efficacious vaccine and that
      the microcarrier/bioreactor platform offers a superior alternative to the
      previously described roller-bottle system.

PMID- 26287532
TI  - Burden of Illness in UK Subjects with Reported Respiratory Infections Vaccinated
      or Unvaccinated against Influenza: A Retrospective Observational Study.
AB  - OBJECTIVE: Detailed data are lacking on influenza burden in the United Kingdom
      (UK). The objective of this study was to estimate the disease burden associated
      with influenza-like illness (ILI) in the United Kingdom stratified by age, risk
      and influenza vaccination status. METHODS: This retrospective, cross-sectional,
      exploratory, observational study used linked data from the General Practice
      Research Database and the Hospital Episode Statistics databases to estimate
      resource use and cost associated with ILI in the UK. RESULTS: Data were included
      from 156,193 patients with >=1 general practitioner visit with ILI. There were
      21,518 high-risk patients, of whom 12,514 (58.2%) were vaccinated and 9,004
      (41.8%) were not vaccinated, and 134,675 low-risk patients, of whom 17,482
      (13.0%) were vaccinated and 117,193 (87.0%) were not vaccinated. High-risk
      vaccinated patients were older (p<0.001) and had more risk conditions (p<0.001).
      High-risk (odds ratio [OR] 2.16) or vaccinated (OR 1.19) patients had a higher
      probability of >1 general practitioner visit compared with low-risk and
      unvaccinated patients. Patients who were high-risk and vaccinated had a reduced
      risk of >1 general practitioner visit (OR 0.82; p<0.001). High-risk individuals
      who were also vaccinated had a lower probability of ILI-related hospitalisation
      than individuals who were high-risk or vaccinated alone (OR 0.59). In people aged
      >=65 years, the mortality rate was lower in vaccinated than unvaccinated
      individuals (OR 0.75). The cost of ILI-related GP visits and hospital admissions
      in the UK over the study period in low-risk vaccinated patients was L27,391,142
      and L141,932,471, respectively. In low-risk unvaccinated patients the
      corresponding values were L168,318,709 and L112,534,130, respectively.
      CONCLUSIONS: Although vaccination rates in target groups have increased, many
      people are still not receiving influenza vaccination, and the burden of ILI in
      the United Kingdom remains substantial. Improving influenza vaccination uptake
      may have the potential to reduce this burden.

PMID- 26287533
TI  - Identification and Clinical Characterization of Adult Patients with
      Multigenerational Diabetes Mellitus.
AB  - BACKGROUND: Some patients diagnosed as having type 2 diabetes mellitus (T2DM)
      are, instead, affected by multigenerational diabetes whose clinical
      characteristics are mostly undefined. OBJECTIVE: 1. To identify among patients
      who had been previously defined as affected by T2DM those, in fact, affected by
      multigenerational diabetes; 2. After excluding patients carrying the most common
      MODY genes and mitochondrial mutations, we compared clinical features of
      remaining patients with those of patients with T2DM. METHODS: Among 2,583
      consecutive adult patients who had been defined as affected by T2DM, we looked
      for those with diabetes in >=3 consecutive generations. All probands were
      screened for mutations in six MODY genes (HNF4A, GCK, HNF1A, PDX1, HNF1B and
      NeuroD1) and for the A3243G mitochondrial mutation. After excluding patients with
      mutations in one of such genes, we compared clinical features of the remaining 67
      patients (2.6% of the whole initial sample) affected by multigenerational
      "familial diabetes of the adulthood" (FDA) and of their diabetic relatives (n =
      63) to those with T2DM (n = 1,028) by generalized hierarchical linear models
      followed by pairwise comparisons. RESULTS: Age, age at diagnosis, proportion of
      hypertension (all p<0.001), and waist circumference (p<0.05) were lower in FDA
      than T2DM. Nonetheless, the two groups had similar age-adjusted incidence rate of
      all-cause mortality. CONCLUSIONS: Beside younger age at diagnosis, FDA patients
      show lower waist circumference and reduced proportion of hypertension as compared
      to those with T2DM; despite such reduced potential cardiovascular risk factors,
      FDA patients did not show a reduced mortality risk than patients with T2DM.

PMID- 26287534
TI  - Body Size Regression Formulae, Proximate Composition and Energy Density of
      Eastern Bering Sea Mesopelagic Fish and Squid.
AB  - The ecological significance of fish and squid of the mesopelagic zone (200 m-1000
      m) is evident by their pervasiveness in the diets of a broad spectrum of upper
      pelagic predators including other fishes and squids, seabirds and marine mammals.
      As diel vertical migrators, mesopelagic micronekton are recognized as an
      important trophic link between the deep scattering layer and upper surface
      waters, yet fundamental aspects of the life history and energetic contribution to
      the food web for most are undescribed. Here, we present newly derived regression
      equations for 32 species of mesopelagic fish and squid based on the relationship
      between body size and the size of hard parts typically used to identify prey
      species in predator diet studies. We describe the proximate composition and
      energy density of 31 species collected in the eastern Bering Sea during May 1999
      and 2000. Energy values are categorized by body size as a proxy for relative age
      and can be cross-referenced with the derived regression equations. Data are
      tabularized to facilitate direct application to predator diet studies and food
      web models. 

PMID- 26287535
TI  - Western Blotting Inaccuracies with Unverified Antibodies: Need for a Western
      Blotting Minimal Reporting Standard (WBMRS).
AB  - Western blotting is a commonly used technique in biological research. A major
      problem with Western blotting is not the method itself, but the use of poor
      quality antibodies as well as the use of different experimental conditions that
      affect the linearity and sensitivity of the Western blot. Investigation of some
      conditions that are commonly used and often modified in Western blotting, as well
      as some commercial antibodies, showed that published articles often fail to
      report critical parameters needed to reproduce the results. These parameters
      include the amount of protein loaded, the blocking solution and conditions used,
      the amount of primary and secondary antibodies used, the antibody incubation
      solutions, the detection method and the quantification method utilized. In the
      present study, comparison of ubiquitinated proteins in rat heart and liver
      samples showed different results depending on the antibody utilized. Validation
      of five commercial ubiquitin antibodies using purified ubiquitinated proteins,
      ubiquitin chains and free ubiquitin showed that these antibodies differ in their
      ability to detect free ubiquitin or ubiquitinated proteins. Investigating
      proteins modified with interferon-stimulated gene 15 (ISG15) in young and old rat
      hearts using six commercially available antibodies showed that most antibodies
      gave different semi-quantitative results, suggesting large variability among
      antibodies. Evidence showing the importance of the Western blot buffer and the
      concentration of antibody used is presented. Hence there is a critical need for
      comprehensive reporting of experimental conditions to improve the accuracy and
      reproducibility of Western blot analysis. A Western blotting minimal reporting
      standard (WBMRS) is suggested to improve the reproducibility of Western blot
      analysis. 

PMID- 26287537
TI  - [The Swiss Society of Ophthalmology meets in Freiburg].

PMID- 26287536
TI  - Dezocine for Preventing Postoperative Pain: A Meta-Analysis of Randomized
      Controlled Trials.
AB  - BACKGROUND: Dezocine is considered to be an alternative medication for managing
      postoperative pain. The aim of this study was to assess the efficacy and safety
      of this drug in this regard. METHODS: Medline, EMBASE and the Cochrane Central
      Register of Control Trials (CENTRAL) were searched to identify all randomized
      controlled trials (RCTs) that compare dezocine with placebo or dezocine with
      morphine on postoperative pain. The data were extracted and pooled using Mantel
      Haenszel random effects model. Heterogeneity was tested using the I2 statistic
      with values >50% and Chi2 test with P <= 0.05 indicating obvious heterogeneity
      between the studies. RESULTS: Seven trials evaluating 665 patients were included.
      The number of patients with at least 50% pain relief was increased (N = 234; RR
      3.04, 95% CI 2.27 to 4.08) and physician (N = 465; RR 2.84, 95% CI 1.66 to 4.84)
      and patient satisfaction (N = 390; RR 2.81, 95% CI 1.85 to 4.26) were improved
      following the administration of dezocine compared with the placebo. The effects
      of dezocine were similar to those of morphine in terms of the number of patients
      reporting at least 50% pain relief within 2-6 h after surgery (N = 235; RR 1.29,
      95% CI 1.15 to 1.46) and physician (N = 234; RR 1.18, 95% CI 0.93 to 1.49) and
      patient (N = 158; RR 1.33, 95% CI 0.93 to 1.92) satisfaction. While, the number
      of patients with at least 50% pain relief within 0-1 h after surgery increased
      following dezocine compared with morphine treatment (N = 79; RR 1.45, 95% CI 1.18
      to 1.77). There was no difference in the incidence of postoperative nausea and
      vomiting (PONV) following dezocine treatment compared with the placebo (N = 391;
      RR 1.06, 95% CI 0.42 to 2.68) or morphine treatment (N = 235; RR 0.65, 95% CI
      0.14 to 2.93). CONCLUSION: Dezocine is a promising analgesic for preventing
      postoperative pain, but further studies are required to evaluate its safety.

PMID- 26287538
TI  - [Variations of IOL].

PMID- 26287539
TI  - [Impact of an Aspherical Aberration Correcting Monofocal Intraocular Lens on
      Patient Satisfaction for Daily Life Activities: The Heidelberg Daily Task
      Evaluation (DATE) Questionnaire].
AB  - BACKGROUND: A clinical evaluation of the functional results and its impact on
      daily activities of an aspherical, aberration correcting intraocular lens (IOL)
      was undertaken. PATIENTS/METHODS: Twenty-one patients aged from 50 to 83 years
      underwent cataract surgery with implantation of the aspheric IOL (Tecnis ZCB00,
      Abbott Medical Optics). They were evaluated 2 to 4 months after surgery for their
      subjective satisfaction of vision quality and its impact on performance of daily
      activities as well as functional results and refractive outcome. Patients were
      asked to fill out a questionnaire - the Heidelberg DATE (DAily Tasks Evaluation)
      questionnaire. RESULTS: Significant changes from pre- to postoperative results
      were found in refraction (p <= 0.03), with a mean prediction error of + 0.21 +/-
      0.43 D. UDVA and CDVA improved significantly (p < 0.01), with a postoperative
      CDVA of 0.0 logMAR or better in 97.1 % of eyes. All patients would recommend the
      procedure to a relative or a friend and 93.8 % of patients reported to be
      satisfied with the outcome. CONCLUSION: The implantation of the aspheric IOL
      Tecnis ZCB00 after cataract surgery allows the restoration of visual function,
      providing an optimised optical quality and a high level of patient satisfaction.

PMID- 26287540
TI  - [Functional Results One Year after Implantation of a Bitoric, Trifocal
      Intraocular Lens].
AB  - PURPOSE: An evaluation of the visual and refractive results was undertaken one
      year after implantation of a trifocal diffractive toric intraocular lens (IOL)
      during cataract surgery. METHODS: In a prospective study patients with a
      calculated postoperative corneal astigmatism of >= 0.75 D received a diffractive
      trifocal toric IOL (AT LISA tri toric 939MP, Carl Zeiss Meditech, Jena, Germany)
      during cataract surgery. One year postoperatively the near, intermediate and
      distance visual acuity, corrected and uncorrected vision as well as refraction
      were evaluated. RESULTS: 20 patients (40 eyes) with a median age of 59 +/- 11
      years of which 15 were female underwent bilateral cataract surgery. One year
      postoperatively a binocular uncorrected distance visual acuity (UDVA) of 0.10
      logMAR +/- 0.11 and a corrected distance visual acuity (CDVA) of 0.00 logMAR +/-
      0.08 could be found. Binocular intermediate visual acuity (UIVA) and near visual
      acuity (UNVA) were 0.00 logMAR +/- 0.05 and 0.09 logMAR +/- 0.07, respectively.
      100 % of patients were between +/- 1.0 D from target refraction. Even 1 year
      after surgery no patient had an IOL rotation greater than 5 degrees . CONCLUSION:
      The implantation of a trifocal toric intraocular lens offers an effective way for
      visual rehabilitation in near, intermediate and far distances with a good
      rotational stability of the IOL platform.

PMID- 26287541
TI  - [Intraocular Lens Opacification Following Posterior Lamellar Keratoplasty].
AB  - BACKGROUND: The opacification of an artificial intraocular lens is a rare but
      serious complication following cataract surgery as an exchange of the intraocular
      lens can become necessary. At our eye center we observed single cases of IOL
      opacifications following complicated posterior lamellar keratoplasty (Descemet
      stripping automated endothelial keratoplasty = DSAEK or Descemet membrane
      endothelial keratoplasty = DMEK). Therefore, we performed a retrospective
      analysis of all our digital charts regarding the incidence of this serious
      complication with respect to posterior lamellar keratoplasty, penetrating
      keratoplasty or sole cataract extraction. METHODS: We searched our digital
      patient database from 2003 to 2015 using the following headings: intraocular
      lens, artificial lens or IOL and opacification or calcification and selected only
      those patients who had undergone either DSAEK, DMEK, penetrating keratoplasty or
      sole cataract surgery (n = 19,565). RESULTS: In total we found five IOL
      opacifications out of 153 DSAEK and two out of 450 DMEK cases, respectively. Five
      of these seven cases had a complicated clinical course with repeated rebubbling
      or additional intraocular surgery (i.e., repeat DSAEK or DMEK or secondary
      penetrating keratoplasty). There were no documented IOL opacifications following
      penetrating keratoplasty or sole cataract extraction. In two cases intraocular
      lens exchange became necessary. All opacifications showed similar clinical
      appearance in form of small granular deposits on the surface of the intraocular
      lens. Almost all implanted lenses were made from hydrophilic acrylate.
      DISCUSSION: In total we found seven cases of intraocular lens opacification that
      have only been observed following DSAEK or DMEK. According to reports from the
      literature these opacifications are superficial calicifications of the
      hydrophilic lenses. As five of the seven cases had a complicated clinical course,
      the repeated air contact of the lens could be one major factor in inducing the
      calcification. Besides the air contact a breakdown of the blood-aqueous barrier
      could also play a role in the induction of calcium phosphate crystallisation on
      the intraocular lens. The risk of this serious complication in mainly hydrophilic
      intraocular lenses with respect to posterior lamellar keratoplasty should be kept
      in mind for the selection of the type of intraocular lens in patients with
      endothelial diseases or in patients undergoing combined cataract extraction and
      DSAEK/DMEK.

PMID- 26287542
TI  - [Letter to the Editor: The So-Called "Ocular Pressure Flow Analyzer (OPFA)" Gives
      a Measure of the Extensibility of the Eye Wall].

PMID- 26287543
TI  - [Letter to the Editor: New Aspects in the Calibration of Tonometers].

PMID- 26287544
TI  - [Commentary for Letter to the Editor: New Aspects in the Calibration of
      Tonometers].

PMID- 26287545
TI  - [Commentary: "The So-Called 'Ocular Pressure Flow Analyzer (OPFA)' Gives a
      Measure of the Extensibility of the Eye Wall"].

PMID- 26287546
TI  - [Secondary Intraocular Lens Implantation].

PMID- 26287548
TI  - Digging Deep for New Compounds from the Compass Plant, Silphium laciniatum.
AB  - The compass plant, Silphium laciniatum, is an iconic perennial plant of the North
      American tallgrass prairie. The plants of the tallgrass prairie historically have
      been subjected to a number of biological and environmental stresses. Among the
      adaptations developed by S. laciniatum is a large deep taproot. An investigation
      of the secondary metabolites found in the root of a S. laciniatum specimen has
      led to the identification of 15 new terpenoids (3-8, 10-17, and 22), which were
      screened for cytotoxic activity in the NCI-H460 human large-cell lung carcinoma
      cell line. 

PMID- 26287547
TI  - A New Role for LOC101928437 in Non-Syndromic Intellectual Disability: Findings
      from a Family-Based Association Test.
AB  - Non-syndromic intellectual disability (NSID) is mental retardation in persons of
      normal physical appearance who have no recognisable features apart from obvious
      deficits in intellectual functioning and adaptive ability; however, its genetic
      etiology of most patients has remained unknown. The main purpose of this study
      was to fine map and identify specific causal gene(s) by genotyping a NSID family
      cohort using a panel of markers encompassing a target region reported in a
      previous work. A total of 139 families including probands, parents and relatives
      were included in the household survey, clinical examinations and intelligence
      tests, recruited from the Qinba mountain region of Shannxi province, western
      China. A collection of 34 tagged single nucleotide polymorphisms (tSNPs) spanning
      five microsatellite marker (STR) loci were genotyped using an iPLEX Gold assay.
      The association between tSNPs and patients was analyzed by family-based
      association testing (FBAT) and haplotype analysis (HBAT). Four markers
      (rs5974392, rs12164331, rs5929554 and rs3116911) in a block that showed strong
      linkage disequilibrium within the first three introns of the LOC101928437 locus
      were found to be significantly associated with NSID (all P<0.01) by the FBAT
      method for a single marker in additive, dominant and recessive models. The
      results of haplotype tests of this block also revealed a significant association
      with NSID (all P<0.05) using 2-window and larger HBAT analyses. These results
      suggest that LOC101928437 is a novel candidate gene for NSID in Han Chinese
      individuals of the Qinba region of China. Although the biological function of the
      gene has not been well studied, knowledge about this gene will provide insights
      that will increase our understanding of NSID development. 

PMID- 26287549
TI  - Investigation of the Endogenous Stress Response System in Patients with Chronic
      Schizophrenia.
AB  - OBJECTIVE: Cardiophysiological and neuroendocrine studies suggest that the two
      components of the endogenous stress response system, the sympathetic nervous
      system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis, are dysregulated
      in patients with schizophrenia. However, cardiophysiological measures are
      influenced by several confounding factors and the secretion of alpha-amylase in
      saliva is believed to represent a more reliable index of SNS activity. Therefore,
      to characterize the functional status of the SNS and HPA axis in schizophrenia we
      explored the concomitant salivary secretion of cortisol and alpha-amylase.
      METHODS: Saliva cortisol and alpha-amylase levels were measured after awakening
      in 30 patients with chronic schizophrenia and 22 healthy subjects. RESULTS: After
      awakening, saliva cortisol increased in a similar way in both patients and
      healthy controls, while saliva alpha-amylase concentrations showed a clear-cut
      decrease in healthy subjects but not in patients with schizophrenia. No
      significant correlation emerged between biochemical measures and patients'
      demographic or psychopathological characteristics. CONCLUSIONS: These findings
      demonstrate normal activity of the HPA axis with an enhanced SNS tone, which
      suggests a functional dissociation of the two components of the endogenous stress
      response system in patients with chronic schizophrenia. The pathophysiological
      significance of such dysregulation needs further studies to be clarified.

PMID- 26287550
TI  - Modern Paradigms in Neurosurgery: Not Yet the Case for Laparoscopic Catheter
      Insertion Techniques.

PMID- 26287552
TI  - A Mobile Schwannoma of the Cervical Spinal Cord: Case Report and Review of the
      Literature.
AB  - BACKGROUND AND IMPORTANCE: Mobile schwannomas have been reported in the lumbar
      spine and occasionally in the thoracic spine. However, to the best of our
      knowledge, this is the first known report of a cervical mobile schwannoma. Mobile
      schwannomas require careful preoperative and intraoperative evaluation of their
      localization because tumor mobility may result in surgery at the wrong level.
      CLINICAL PRESENTATION: A 68-year-old man had complained of clumsiness in his left
      hand for 10 years. An initial magnetic resonance image (MRI) showed an intradural
      extramedullary tumor at the C5 to C7 levels, deformation of the adjacent spinal
      cord, and unusual dilatation of the subarachnoid space from the C7 to T1 levels.
      A subsequent MRI revealed that the tumor had moved to the C6 to T1 levels. We
      diagnosed the lesion as a mobile tumor of the cervical spinal cord. The patient
      underwent a C6-C7 laminectomy with an additional partial laminectomy of C5 and
      T1. Intraoperative ultrasonography helped localize the tumor. Transdural
      ultrasonography and direct observation confirmed the tumor mobility. The tumor
      was completely removed. The histological diagnosis was schwannoma. CONCLUSION: We
      observed an extremely rare case of a mobile schwannoma of the cervical spine.
      Unusually dilated subarachnoid space adjacent to the tumor can be a diagnostic
      sign of tumor mobility, regardless of vertebral level. Repeated MRI studies are
      useful to preoperatively confirm tumor mobility. Intraoperative ultrasonography
      is valuable for the real-time localization of such mobile tumors to avoid
      potentially performing surgery at the wrong vertebral level.

PMID- 26287554
TI  - In Reply: Modern Paradigms in Neurosurgery: Not Yet the Case for Laparoscopic
      Catheter Insertion Techniques.

PMID- 26287555
TI  - Resolution of Oculomotor Nerve Palsy Secondary to Posterior Communicating Artery
      Aneurysms: Comparison of Clipping and Coiling.
AB  - BACKGROUND: Previous studies have attempted to determine the best treatment for
      oculomotor nerve palsy (ONP) secondary to posterior communicating artery (PCoA)
      aneurysms, but have been limited by small sample sizes and limited treatment.
      OBJECTIVE: To analyze the treatment of ONP secondary to PCoA with both coiling
      and clipping in ruptured and unruptured aneurysms. METHODS: Data from 2 large
      academic centers was retrospectively collected over 22 years, yielding a total of
      93 patients with ONP secondary to PCoA aneurysms. These patients were combined
      with 321 patients from the literature review for large data analyses. Onset
      symptoms, recovery, and time to resolution were evaluated with respect to
      treatment and aneurysm rupture status. RESULTS: For all patients presenting with
      ONP (n = 414) 56.6% of those treated with microsurgical clipping made a full
      recovery vs 41.5% of those treated with endovascular coil embolization (P = .02).
      Of patients with a complete ONP (n = 229), full recovery occurred in 47.3% of
      those treated with clipping but in only 20% of those undergoing coiling (P =
      .01). For patients presenting with ruptured aneurysms (n = 130), full recovery
      occurred in 70.9% compared with 49.3% coiled patients (P = .01). Additionally,
      although patients with full ONP recovery had a median time to treatment of 4
      days, those without full ONP recovery had a median time to treatment of 7 days (P
      = .01). CONCLUSION: Patients with ONP secondary to PCoA aneurysms treated with
      clipping showed higher rates of full ONP resolution than patients treated with
      coil embolization. Larger prospective studies are needed to determine the true
      potential of recovery associated with each treatment. ABBREVIATIONS: EUH, Emory
      University HospitalIQR, interquartile rangeJHU, Johns Hopkins UniversitymRS,
      modified Rankin ScaleONP, oculomotor nerve palsyPCoA, posterior communicating
      arterySAH, subarachnoid hemorrhage.

PMID- 26287556
TI  - Safety and Efficacy of Surgical Resection of Unruptured Low-grade Arteriovenous
      Malformations From the Modern Decade.
AB  - BACKGROUND: Recent studies have questioned the utility of surgical resection of
      unruptured brain arteriovenous malformations (bAVMs). OBJECTIVE: We performed an
      assessment of outcomes and complications of surgical resection of low-grade bAVMs
      (Spetzler-Martin grade I or II) at a single high-volume neurosurgical center.
      METHODS: We reviewed all unruptured low-grade bAVMs treated with surgery (with or
      without preoperative embolization) between January 2004 and January 2014. Stroke
      rate, mortality, and clinical and radiographic outcomes were examined. RESULTS:
      Of 95 patients treated surgically, 85 (25 grade I, 60 grade II) met inclusion
      criteria, and all achieved radiographic cure postoperatively. Ten patients
      (11.8%) were lost to follow-up; the mean follow-up of the remaining 85 was 3.3
      years. Three patients (3.5%) with grade II bAVMs experienced a stroke; no
      patients died. Although 20 patients (23.5%) had temporary postoperative
      neurological deficit, only 3 (3.5%) had new clinical impairment (modified Rankin
      Scale score >=2) at last follow-up. Eight of the 13 patients (61.5%) with
      preexisting clinical impairment had improved modified Rankin Scale scores of 0 or
      1; and 17 of 30 patients (56.7%) with preoperative seizures were seizure-free
      without antiepileptic medication postoperatively. No significant differences
      existed in stroke rate or clinical outcome between grades I and II patients at
      follow-up (Fisher exact test, P = .55 and P > .99, respectively). CONCLUSION:
      Surgical resection of low-grade unruptured bAVMs is safe, with a high rate of
      improvement in functional status and seizure reduction. Although transient
      postoperative neurological deficit was observed in some patients, permanent
      treatment-related neurological morbidity was rare. ABBREVIATIONS: ARUBA, A
      Randomized Trial of Unruptured Brain Arteriovenous MalformationsbAVM, brain
      arteriovenous malformationmRS, modified Rankin Scale.

PMID- 26287557
TI  - Human tail: a rare feature of amniotic band syndrome?

PMID- 26287558
TI  - Inherited duplication of the short arm of chromosome 18p11.32-p11.31 associated
      with developmental delay/intellectual disability.
AB  - Duplications of 18p have been reported in the literature associated with a range
      of different abnormalities and also in patients with normal phenotypes. The
      majority of these reports are based solely on G-banded cytogenetic evaluation.
      The use of arrayCGH characterization has improved the ability to define regions
      of imbalance and is helping to identify potential underlying triplosufficiency of
      any duplicated genes. We report on a family where the father and his two
      daughters all have a duplication 18p11.32-p11.31 characterized by microarray.
      They present with variable levels of intellectual disability/developmental delay
      and behavioural difficulties without any physical anomalies. This family
      contributes toward the growing knowledge of pure duplications of 18p and provides
      information on interpretation of novel array findings in the context of family
      history. It also reiterates the importance of elucidating a detailed learning and
      developmental phenotype and family pedigree in aiding interpretation of genetic
      testing results. 

PMID- 26287559
TI  - Neuromyelitis optica spectrum disorders may be misdiagnosed as Wernicke's
      encephalopathy.
AB  - PURPOSE: To raise doctors' attention to the differential diagnosis of
      neuromyelitis optica spectrum disorders (NMOSD) and Wernicke's encephalopathy
      (WE). PATIENTS AND METHODS: We extensively reviewed the medical records of 136
      patients who had visited our hospital since 2008 and were suspected of having
      central nervous system demyelinating diseases. Four of those patients had
      somnolence, electrolyte imbalance and brain lesions around the third ventricle
      and were included in the study. We tested the serum of the four patients for the
      presence of aquaporin-4 (AQP4) M23 antibody. RESULTS: All the four patients had
      positive AQP4 antibody in their serum. Two of the patients were misdiagnosed as
      WE before AQP4 antibody detection occurred. CONCLUSIONS: NMOSD and WE have
      similar brain lesion locations, histopathological changes and clinical
      manifestations. It is important to distinguish NMOSD from WE by detecting AQP4
      antibody in serum or cerebral spinal fluid. Vitamin B1 should also be
      administered to the patients who have a history of thiamine deficiency.

PMID- 26287560
TI  - Quencher group induced high specificity detection of telomerase in clear and
      bloody urines by AIEgens.
AB  - Telomerase is a widely used tumor biomarker for early cancer diagnosis. On the
      basis of the combined use of aggregation-induced emission (AIE) fluorogens and
      quencher, a quencher group induced high specificity strategy for detection of
      telomerase activity from cell extracts and cancer patients' urine specimens was
      creatively developed. In the absence of telomerase, fluorescence background is
      extremely low due to the short distance between quencher and AIE dye. In the
      addition of telomerase, fluorescence enhances significantly. The telomerase
      activity in the E-J, MCF-7, and HeLa extracts equivalent to 5-10 000 cells can be
      detected by this method in ~1 h. Furthermore, the distinguishing of telomerase
      extracted from 38 cancer and 15 normal urine specimens confirms the reliability
      and practicality of this protocol. In contrast to our previous results (Anal.
      Chem. 2015, 87, 6822-6827), these advanced experiments obtain more remarkable
      specificity. 

PMID- 26287561
TI  - Unexpected Formation of NHC-Stabilized Hydrosilylyne Complexes via Alkane
      Elimination from NHC-Stabilized Hydrido(alkylsilylene) Complexes.
AB  - N-heterocyclic carbene (NHC)-stabilized hydrosilylyne complex
      Cp*(CO)2WSiH((Me)IMe)2 (3a) ((Me)IMe = 1,3,4,5-tetramethylimidazole-2-ylidene)
      was formed by the reaction of an NHC-stabilized silylene complex
      Cp*(CO)2(H)WSiH((Me)IMe){C(SiMe3)3} (2a) with 1 equiv of (Me)IMe at 70  degrees
      C. In this reaction, HC(SiMe3)3 was unexpectedly eliminated from 2a. A C5Me4Et
      analogue of 3a, (C5Me4Et)(CO)2WSiH((Me)IMe)2 (3b), was also synthesized by the
      same method, and the structure of 3b was confirmed by X-ray crystallography.
      Although the silicon center of 3b is coordinated by two NHCs, the length of the W
      Si bond of 3b [2.363(4) A] is as short as that of the shortest W?Si double bond
      (~2.36 A). These complexes, 3a and 3b, are the first examples of a base
      stabilized silylyne complex having only a hydrogen on the silicon atom. 

PMID- 26287562
TI  - Pestaloporonins: Caryophyllene-Derived Sesquiterpenoids from a Fungicolous
      Isolate of Pestalotiopsis sp.
AB  - Three new sesquiterpenoids (pestaloporonins A-C; 1-3) related to the
      caryophyllene-derived punctaporonins were isolated from cultures of a fungicolous
      isolate of Pestalotiopsis sp. The structures of 1-3 were determined by analysis
      of NMR and HRMS data, and the structure of 1, including its absolute
      configuration, was confirmed by X-ray crystallographic analysis. Compounds 1 and
      2 contain new bicyclic and tricyclic ring systems, respectively. 

PMID- 26287564
TI  - Race, Pain, and Beliefs Associated with Interest in Complementary and Alternative
      Medicine among Inner City Veterans.
AB  - OBJECTIVE: To investigate the prevalence and determinants of complementary and
      alternative medicine (CAM) interest level among a racially diverse cohort of
      inner city veterans who receive primary care at the VA Medical Center. DESIGN:
      Cross-sectional survey study SETTING: Philadelphia VA Medical Center SUBJECTS:
      Primary care patients (n = 258) METHODS: Interest in CAM was measured using a
      single item question. Patient treatment beliefs were assessed using validated
      instruments. We evaluated factors associated with patient interest in CAM using a
      multivariate logistic regression model. RESULTS: In this sample of 258 inner city
      primary care VA patients, interest in CAM was high 80% (n = 206). Interest in CAM
      was strongly associated with African American race [adjusted odds ratio (AOR)
      2.19, 95% Confidence Interval (CI) 1.05-4.60, P = 0.037], higher levels of
      education (AOR 4.33, 95% CI 1.80-10.40, P = 0.001), presence of moderate to
      severe pain (AOR 2.02, 95% CI 1.02-4.78, P = 0.043), and expectations of benefit
      from CAM use (AOR 1.21, 95% CI 1.06-1.36, P = 0.004). CONCLUSIONS: CAM approaches
      have broad appeal within this inner city cohort of veterans, particularly among
      African Americans, those that experience pain and those that expect greater
      benefit from CAM. These findings may inform the development of patient-centered
      integrative pain management for veterans.

PMID- 26287565
TI  - Abnormal lipid rafts related ganglioside expression and signaling in T
      lymphocytes in immune thrombocytopenia patients.
AB  - Aberrant T lymphocytes signaling is considered to play a crucial role in the
      abnormal immune state of primary immune thrombocytopenia (ITP). Lipid raft has
      been verified to engage in the T cell receptor (TCR)-mediated T lymphocytes
      signal transduction. Whether lipid raft-associated T cells signal transduction
      has impact on the pathogenesis of ITP is still unconfirmed. In this study, we
      aimed to reveal the abnormality in structure and function of lipid rafts (LRs) in
      CD4(+) and CD8(+) T lymphocytes of patients with ITP. Our results showed that
      there was an increased lipid raft aggregation in ITP patients, while this kind of
      increase would not be influenced by platelet counts or therapeutic regimes.
      Stimulation by anti-CD3/CD28 monoclonal antibodies promoted enhanced lipid raft
      clustering in T lymphocytes of ITP patients compared with negative controls.
      Methyl-beta-cyclodextrin (MbetaCD) could block the abnormal lipid raft
      aggregation and disrupt the TCR-mediated T cells proliferation and cytokines
      secretion, including both proinflammatory cytokines and anti-inflammatory
      cytokines. The spontaneous activation of T lymphocytes from ITP patients might be
      due to the elevated co-localization of protein tyrosine phosphatase (PTP) CD45
      and lipid rafts in patients' CD4(+) and CD8(+) T lymphocytes. These findings
      suggest that the autoactivation of T lymphocytes from ITP patients may lead to
      the abnormality in lipid raft structure and raft-anchored proteins, and the
      changes conversely promote the TCR-mediated T cells activation of ITP patients. 

PMID- 26287566
TI  - Treatment-induced hearing loss and adult social outcomes in survivors of
      childhood CNS and non-CNS solid tumors: Results from the St. Jude Lifetime Cohort
      Study.
AB  - BACKGROUND: Survivors of childhood cancer who are treated with platinum-based
      chemotherapy and/or cranial radiation are at risk of treatment-induced hearing
      loss. However, the effects of such hearing loss on adult social attainment have
      not been well elucidated. METHODS: Adult survivors of pediatric central nervous
      system (CNS) solid tumors (180 survivors) and non-CNS solid tumors (226
      survivors) who were treated with potentially ototoxic cancer therapy completed
      audiologic evaluations and questionnaires assessing their perception of social
      functioning and social attainment (ie, independent living, marriage, and
      employment). Audiograms were graded with the Chang ototoxicity grading scale.
      Analyses were stratified by tumor type (ie, CNS vs non-CNS). Multivariable
      logistic regression models were conducted with adjustment for age; sex; chronic
      health conditions; and, for the CNS group, IQ. Adjusted odds ratios (ORs) and 95%
      confidence intervals (95% CIs) were reported. RESULTS: Serious hearing loss (that
      requiring a hearing aid or deafness) was detected in 36% of survivors of CNS
      tumors and 39% of survivors of non-CNS tumors. Serious hearing loss was
      associated with an increased risk of perceived negative impact in >=1 areas of
      social functioning (survivors of non-CNS tumors: OR, 1.83 [95% CI, 1.00-3.34]).
      Among survivors of non-CNS tumors, serious hearing loss was associated with 2
      fold increased risk of nonindependent living (OR, 2.19; 95% CI, 1.19-4.04) and
      unemployment or not graduating from high school (OR, 1.85; 95% CI, 1.00-3.34).
      CONCLUSIONS: A substantial proportion of adult survivors of childhood cancer
      treated with potentially ototoxic therapy have serious hearing loss. Treatment
      induced hearing loss was found to be associated with reduced social attainment,
      both perceived and actual, in this study sample.

PMID- 26287567
TI  - Highly Fluorescent Gene Carrier Based on Ag-Au Alloy Nanoclusters.
AB  - For systemic delivery of gene, gold nanoparticles (GNPs) have been exploited as
      novel gene carriers because of the excellent characteristics for "visible" in
      intracellular trafficking. Herein, a highly fluorescent gene carrier was prepared
      by conjugating polyethylenimines on Ag-Au alloy nanoclusters. This carrier
      exhibited remarkable high gene transfection efficiencies and relatively low
      cytotoxicity toward B16F10, HeLa, and CHO cells. More interestingly, the high
      fluorescent Ag-Au-PEI conjugates showed high quantum yield of 14.56%, which is
      much higher than most of the reported gold nanocluster-based quantum dots and Ag
      Au-PEI possessed bioimaging capacity both in vitro and in vivo. 

PMID- 26287568
TI  - Nanostructured Materials Prepared by Surface-Assisted Reduction: New Catalysts
      for Methane Oxidation.
AB  - Cerium formate hollow spheres and cerium hydroxycarbonate nanorods with residual
      formate groups are effective for reducing palladium(II) salts onto their
      surfaces. Calcination of the new materials obtained by this surface-assisted
      reduction method gives highly active PdO/CeO2 nanostructures with Pd well
      dispersed on the substrate. Temperature-programmed oxidation experiments showed
      that these nanomaterials are good catalysts for the low-temperature oxidation of
      methane, with 50% conversion temperatures (T(50%)) at ~300  degrees C.

PMID- 26287569
TI  - Morphological analysis of the early development of telencephalic and diencephalic
      gonadotropin-releasing hormone neuronal systems in enhanced green fluorescent
      protein-expressing transgenic medaka lines.
AB  - Teleosts possess two or three paralogs of gonadotropin-releasing hormone (GnRH)
      genes: gnrh1, gnrh2, and gnrh3. Some species have lost the gnrh1 and/or gnrh3
      genes, whereas gnrh2 has been completely conserved in the teleost species
      analyzed to date. In most teleosts that possess gnrh1, GnRH1 peptide is the
      authentic GnRH that stimulates gonadotropin release, whereas GnRH2 and GnRH3, if
      present, are neuromodulatory. Progenitors of GnRH1 and GnRH3 neurons originate
      from olfactory placodes and migrate to their destination during early
      development. However, because of the relatively low affinity/specificity of
      generally available antibodies that recognize GnRH1 or GnRH3, labeling of these
      neurons has only been possible using genetic manipulation. We used a model
      teleost, medaka, which possesses all three paralogous gnrh genes, to analyze
      development of forebrain GnRH neurons composed of GnRH1 and GnRH3 neurons. Here,
      we newly generated transgenic medaka lines that express enhanced green
      fluorescent protein under the control of promoters for gnrh1 or gnrh3, to detect
      GnRH neurons and facilitate immunohistochemical analysis of the neuronal
      morphology. We used a combination of immunohistochemistry and three-dimensional
      confocal microscopy image reconstructions to improve identification of neurites
      from GnRH1 or GnRH3 neuronal populations with greater precision. This led us to
      clearly identify the hypophysiotropic innervation of GnRH1 neurons residing in
      the ventral preoptic area (vPOA) from as early as 10 days post hatching.
      Furthermore, these analyses also revealed retinopetal projections of
      nonhypophysiotropic GnRH1 neurons in vPOA, prominent during early developmental
      stages, and multiple populations of GnRH3 neurons with different origins and
      migratory pathways.

PMID- 26287570
TI  - EAACI position paper for practical patch testing in allergic contact dermatitis
      in children.
AB  - INTRODUCTION: Allergic contact dermatitis (ACD) in children appears to be on the
      increase, and contact sensitization may already begin in infancy. The diagnosis
      of contact dermatitis requires a careful evaluation of a patient's clinical
      history, physical examination, and skin testing. Patch testing is the gold
      standard diagnostic test. METHODS: Based on consensus, the EAACI Task Force on
      Allergic Contact Dermatitis in Children produced this document to provide details
      on clinical aspects, the standardization of patch test methodology, and
      suggestions for future research in the field. RESULTS: We provide a baseline list
      of test allergens to be tested in children with suspected ACD. Additional tests
      should be performed only on specific indications.

PMID- 26287571
TI  - Protein Cross-Linking and Oligomerization through Dityrosine Formation upon
      Exposure to Ozone.
AB  - Air pollution is a potential driver for the increasing prevalence of allergic
      disease, and post-translational modification by air pollutants can enhance the
      allergenic potential of proteins. Here, the kinetics and mechanism of protein
      oligomerization upon ozone (O3) exposure were studied in coated-wall flow tube
      experiments at environmentally relevant O3 concentrations, relative humidities
      and protein phase states (amorphous solid, semisolid, and liquid). We observed
      the formation of protein dimers, trimers, and higher oligomers, and attribute the
      cross-linking to the formation of covalent intermolecular dityrosine species. The
      oligomerization proceeds fast on the surface of protein films. In the bulk
      material, reaction rates are limited by diffusion depending on phase state and
      humidity. From the experimental data, we derive a chemical mechanism and rate
      equations for a kinetic multilayer model of surface and bulk reaction enabling
      the prediction of oligomer formation. Increasing levels of tropospheric O3 in the
      Anthropocene may promote the formation of protein oligomers with enhanced
      allergenicity and may thus contribute to the increasing prevalence of allergies. 

PMID- 26287572
TI  - In vivo evidence of hippocampal dentate gyrus expansion in multiple sclerosis.
AB  - Using MR-based radial mapping, we assessed morphological alterations of the
      hippocampal dentate gyrus (DG) in patients with relapse-onset multiple sclerosis
      (MS). We analyzed different stages of the disease and the association of DG
      alterations with hippocampal-related cognitive functions. Using high-resolution
      morphological imaging, hippocampal radial mapping analysis was performed in 28
      relapsing-remitting (RR), 34 secondary progressive, and 26 benign MS patients and
      28 healthy controls (HC). Between-groups differences of DG radial distance (from
      surface points to the central core of the hippocampus) and correlations with
      clinical, neuropsychological, and radiological measures were evaluated using
      surface-based mesh modeling. Compared with HC, all MS clinical phenotypes
      revealed a larger radial distance of the DG, which was more marked on the left
      side. Radial distance enlargement was more pronounced in RRMS patients compared
      with the other disease clinical phenotypes and was inversely correlated to
      disease duration. Radial distance enlargement was correlated with higher T2
      lesion volume and a better cognitive performance in RRMS and with a poor
      cognitive performance in secondary progressive and benign MS patients. Surface
      expansion of the DG might represent an inflammation-induced neurogenic (reactive)
      process of the subgranular zone of the hippocampus primarily aimed at rescuing
      the functional competence of hippocampal circuitry.

PMID- 26287573
TI  - Slope-Dependent Cell Motility Enhancements at the Walls of PEG-Hydrogel
      Microgroove Structures.
AB  - In recent years, research utilizing micro- and nanoscale geometries and
      structures on biomaterials to manipulate cellular behaviors, such as
      differentiation, proliferation, survival, and motility, have gained much
      popularity; however, how the surface microtopography of 3D objects, such as
      implantable devices, can affect these various cell behaviors still remains
      largely unknown. In this study, we discuss how the walls of microgroove
      topography can influence the morphology and the motility of unrestrained cells,
      in a different fashion from 2D line micropatterns. Here adhesive substrates made
      of tetra(polyethylene glycol) (tetra-PEG) hydrogels with microgroove structures
      or 2D line micropatterns were fabricated, and cell motility on these substrates
      was evaluated. Interestingly, despite being unconstrained, the cells exhibited
      drastically different migration behaviors at the edges of the 2D micropatterns
      and the walls of microgroove structures. In addition to acquiring a unilamellar
      morphology, the cells increased their motility by roughly 3-fold on the
      microgroove structures, compared with the 2D counterpart or the nonpatterned
      surface. Immunostaining revealed that this behavior was dependent on the
      alignment and the aggregation of the actin filaments, and by varying the slope of
      the microgroove walls, it was found that relatively upright walls are necessary
      for this cell morphology alterations. Further progress in this research will not
      only deepen our understanding of topography-assisted biological phenomena like
      cancer metastasis but also enable precise, topography-guided manipulation of cell
      motility for applications such as cancer diagnosis and cell sorting. 

PMID- 26287574
TI  - Low-dose chloroquine is associated with favourable effects on lipoprotein
      metabolism without significant influence on insulin resistance.

PMID- 26287575
TI  - Dried blood spots of pooled samples for RHD gene screening in blood donors of
      mixed ancestry.
AB  - OBJECTIVES: In this study, we present a strategy for RHD gene screening based on
      real-time polymerase chain reaction (PCR) using dried blood spots of pooled
      samples. BACKGROUND: Molecular analysis of blood donors may be used to detect RHD
      variants among the presumed D-negative individuals. RHD genotyping using pooled
      samples is a strategy to test a large number of samples at a more reasonable
      cost. MATERIALS AND METHODS: RHD gene detection based on real-time PCR using
      dried blood spots of pooled samples was standardised and used to evaluate 1550
      Brazilian blood donors phenotyped as RhD-negative. Positive results were re
      evaluated by retesting single samples using real-time PCR and conventional
      multiplex PCR to amplify five RHD-specific exons. PCR-sequence-specific primers
      was used to amplify RHDpsi allele. RESULTS: We devised a strategy for RHD gene
      screening using dried blood spots of five pooled samples. Among 1550
      serologically D-negative blood donors, 58 (3.74%) had the RHD gene. The non
      functional RHDpsi allele was detected in 47 samples (3.02%). CONCLUSION: The
      present method is a promising strategy to detect the RHD gene among presumed RhD
      negative blood donors, particularly for populations with African ancestry.

PMID- 26287576
TI  - Intercorrelation of Electronic, Structural, and Morphological Properties in
      Nanorods of 2,3,9,10-Tetrafluoropentacene.
AB  - We evidence the intercorrelation of electronic, structural, and morphological
      properties in nanorods of a substituted fluorine-based pentacene, 2,3,9,10
      tetrafluoropentacene, deposited on gold single crystals by using photoemission
      and X-ray absorption spectroscopy investigations. Our investigations show changes
      in the XPS spectroscopy lines, and NEXAFS features correlate with the specific
      structure of the assemblies and their morphology. Consequently, the chemical
      structure affects not only the molecular electronic structure and the way the
      molecules assemble in a film but also the film morphology leading to specific
      thin film electronic properties. 

PMID- 26287577
TI  - Cortisol, Health, and Coping in Patients with Nonspecific Low Back Pain.
AB  - Subjective health complaints (SHC), including nonspecific low back pain (LBP) as
      the most common single complaint, are the main reasons for long-term sick leave
      in many western countries. These complaints are often attributed to "stress".
      Cortisol has frequently been considered a biomarker reflecting sustained
      physiological HPA-axis activity, and is characterized by a high cortisol
      awakening response (CAR) and low evening values. The aim of the study was to
      investigate whether LBP patients had a normal characteristic cortisol profile,
      and whether possible deviations were related to coping and health. 305 patients
      on long-term sick leave for LBP participated in the study, and saliva cortisol
      profiles were compared to a reference population consisting of Danish workers.
      Cortisol was measured upon awakening, after 30 min, and in the evening.
      Additionally, patients answered questionnaires about SHC, fatigue, pain, coping,
      and social support. The patients showed a seemingly normal cortisol profile.
      However, CAR was larger among patients compared to the reference population.
      Patients with low cortisol reactivity had more SHC, pain, and fatigue, and those
      with higher evening cortisol reported higher scores on coping. The results are
      discussed in terms of theory, practical considerations, and possible mechanisms
      for the association between cortisol, health, and coping.

PMID- 26287578
TI  - Eye Care Professionals' Perspectives on Eye Donation and an Eye Donation Registry
      for Research: A Single-Institution, Cross-Sectional Study.
AB  - PURPOSE: A centralized eye donation registry for research could help to bridge
      the gap between patients interested in donating their eyes to science and
      scientists who conduct research on human eye tissue. Previous research has
      demonstrated patient and family support for such a registry. In this study, we
      assessed the views that eye care professionals have toward an eye donation
      registry for research. MATERIALS AND METHODS: Surveys were distributed to all 46
      clinical faculty members of the Duke University Eye Center. In addition to
      collecting demographic information, the surveys assessed clinicians' experience
      with discussing eye donation with patients, described the proposed eye donation
      registry for research and asked how the registry would affect the clinicians'
      practice. RESULTS: A total of 21 eye care professionals returned the survey.
      Thirty-three percent reported discussing eye donation with patients, and 43%
      reported that a patient has asked about donating their eyes for research on their
      disease. Eighty-six percent of eye care professionals reported that a centralized
      registry would improve the way they work with patients who express a desire to
      donate their eyes for research. CONCLUSIONS: The majority of eye care
      professionals at our academic institution indicated that an eye donation registry
      for research would improve how they work with patients who are interested in
      donating their eyes for research on their disease. Future research should examine
      how best to communicate this registry to ophthalmic patients.

PMID- 26287579
TI  - Balancing Social Responsibility and Personal Autonomy: Adolescents' Reasoning
      About Community Service Programs.
AB  - Many jurisdictions in North America have implemented mandatory community service
      programs in high schools. However, little research exists examining the reasoning
      of youth themselves about such programs. This study examined how youth reason
      about community service programs, and how they balance the prosocial goals of
      these programs against their personal autonomy. Seventy-two participants between
      10 and 18 years old evaluated voluntary community service along with 4
      hypothetical mandatory programs that varied according to whether students or the
      government decided the areas in which students would serve, and whether a
      structured reflection component was included. The findings reveal that youth are
      not simply self-focused but rather balance and coordinate considerations of
      autonomy and community in their judgments and reasoning about community service.

PMID- 26287580
TI  - Ameliorative effect of betulin from Betula platyphylla bark on scopolamine
      induced amnesic mice.
AB  - Alzheimer's disease (AD) is a neurodegenerative disease induced by cholinergic
      neuron damage or amyloid-beta aggregation in the basal forebrain region and
      resulting in cognitive disorder. We previously reported on the neuroprotective
      effects of Betula platyphylla bark (BPB) in an amyloid-beta-induced amnesic mouse
      model. In this study, we obtained a cognitive-enhancing compound by assessing
      results using a scopolamine-induced amnesic mouse model. Our results show that
      oral treatment of mice with BPB and betulin significantly ameliorated scopolamine
      induced memory deficits in both passive avoidance and Y-maze tests. In the Morris
      water maze test, administration of BPB and betulin significantly improved memory
      and cognitive function indicating the formation of working and reference memories
      in treated mice. Moreover, betulin significantly increased glutathione content in
      mouse hippocampus, and the increase was greater than that from betulinic acid
      treatment. We conclude that BPB and its active component betulin have potential
      as therapeutic, cognitive enhancer in AD.

PMID- 26287582
TI  - Developmental changes in the hypothalamic mRNA levels of prepro-orexin and orexin
      receptors and their sensitivity to fasting in male and female rats.
AB  - Orexin, which is also called as hypocretin (Hcrt), a product of the prepro-orexin
      (pp-orexin//Hcrt) gene, affects various physiological and behavioral functions,
      such as the sleep-wake cycle and appetite. The developmental changes in the
      hypothalamic mRNA levels of pp-prexin and the orexin receptors OX1R and OX2R and
      their sensitivity to fasting were evaluated in both male and female rats. During
      development, hypothalamic pp-orexin/Hcrt mRNA expression increased in both male
      and female rats, whereas hypothalamic OX1R mRNA expression decreased in both
      sexes. In addition, hypothalamic OX2R mRNA expression increased in male rats, but
      did not change in female rats. Fasting did not affect hypothalamic pp-orexin/Hcrt
      mRNA expression in either sex. Hypothalamic OX1R mRNA expression was increased by
      fasting in the prepubertal period (postnatal days 20 and 30) in female rats, but
      was not affected by fasting in males. In male rats, hypothalamic OX2R mRNA
      expression was decreased by fasting during the neonatal period (postnatal day
      10), but not the prepubertal period (postnatal days 20 and 30). In females,
      hypothalamic OX2R mRNA expression was also decreased by fasting; however, the
      fasting-induced downregulation of hypothalamic OX2R expression persisted until
      postnatal day 20. These results indicate that the developmental patterns of
      components of the orexin system and their sensitivity to fasting during the
      neonatal and prepubertal periods only differ slightly between the sexes. These
      differences might be involved in the development of some physiological and
      behavioral functions. 

PMID- 26287581
TI  - Neonatal serotonin reuptake inhibition reduces hypercaloric diet effects on fat
      mass and hypothalamic gene expression in adult rats.
AB  - BACKGROUND: Serotonin (5-HT) is involved in nervous system ontogenesis, and is
      important for neurotransmission and behavior modulation after the developmental
      stage. Alterations in 5-HT levels during the early period of life may signal to
      feeding behavior and hypothalamic genic expression changes in adulthood.
      OBJECTIVES: Investigate the effects of hypercaloric diet in adult rats submitted
      to neonatal serotonin reuptake inhibition on food intake, fat pad mass, plasmatic
      triglycerides/cholesterol and gene expression of hypothalamic peptides (POMC,
      NPY) and serotonin receptors (5-HT1B, 5-HT2C). METHODS: In each litter, 8 pups
      were divided into two groups: control (C) and fluoxetine (F). From the 1(st) to
      the 21(st) postnatal day, C pups received sterile saline while F pups received
      fluoxetine (10mg/kg). From 180 to 215 days, a group of rats from C and F groups
      were fed hypercaloric diet (CH and FH, 421.4Kcal/100 g) while the rest of animals
      from C and F groups fed chow diet (CC and FC). RESULTS: The use of hypercaloric
      diet was associated with lower accumulation of white adipose tissue in adult rats
      subjected to neonatal serotonin reuptake inhibition. Adult rats of group FC
      showed decreased 5-HT2C and neuropeptide Y mRNA expression compared with control
      chow diet group (CC). After chronic use of a hypercaloric diet, the expression of
      5-HT2C was higher in the FH group than the FC group and neuropeptide Y expression
      decreased in FH related to FC. CONCLUSIONS: These findings suggest that neonatal
      serotonin reuptake inhibition is associated with better adaptation to
      hypercaloric diet in adult rats.

PMID- 26287583
TI  - Identification and phylogenetic analysis of the mitogenome of Sarcocheilichthys
      parvus Nichols (Cypriniformes: Cyprinidae).
AB  - In the present study, the complete mitogenome sequence of a Sarcocheilichthys
      parvus Nichols was sequenced and identified. It contained 22 tRNA genes, 13
      protein-coding genes, 2 rRNA genes and 2 non-coding regions. The phylogenetic
      analysis showed that the mitogenome sequence could be useful data in the field of
      systematics and conservation biology for S. parvus Nichols and other aquatic
      species.

PMID- 26287584
TI  - CD8(+) T cell diversification by asymmetric cell division.

PMID- 26287585
TI  - Reply to: "CD8(+) T cell diversification by asymmetric cell division".

PMID- 26287586
TI  - Co-ordination of intrathymic self-representation.

PMID- 26287587
TI  - IL-26 AMPs up the T(H)17 arsenal.

PMID- 26287588
TI  - LRRK2 and Nod2 promote lysozyme sorting in Paneth cells.

PMID- 26287589
TI  - TCF-1 and LEF-1 help launch the T(FH) program.

PMID- 26287590
TI  - Teaching 'big data' analysis to young immunologists.

PMID- 26287598
TI  - Ethylene oligomerization promoted by chromium complexes bearing pyrrolide-imine
      amine/ether tridentate ligands.
AB  - Chromium(iii) complexes [CrCl2(L)(THF)] based on monoanionic tridentate ligands
      [, L = {2-(C4H3N-2'-CH[double bond, length as m-dash]N)C2H4NHPh}; , L = {5-tert
      butyl-2-(C4H2N-2'-CH[double bond, length as m-dash]N)C2H3NHPh}; , L = {2-(C4H3N
      2'-CH[double bond, length as m-dash]N)C2H4OPh}] have been prepared. Complexes and
      were converted into the monomeric acetonitrile adducts [CrCl2(L)(NCMe)] [, L = {2
      (C4H3N-2'-CH[double bond, length as m-dash]N)C2H4NHPh}; , L = {5-tert-butyl-2
      (C4H2N-2'-CH[double bond, length as m-dash]N)C2H3NHPh}] by reaction with
      acetonitrile at room temperature. All Cr complexes were characterized by IR
      spectroscopy, elemental analysis, magnetochemistry for , and by X-ray
      crystallography for and . Upon activation with methylaluminoxane (MAO), chromium
      precatalysts and showed good activity in ethylene oligomerization (TOF = 47.0
      57.0 * 10(3) (mol ethylene)(mol Cr)(-1) h(-1) at 80  degrees C), producing mostly
      oligomers (93.0-95.6 wt% of total products). On the other hand, under identical
      oligomerization conditions, /MAO behaved as a polymerization catalyst generating
      predominantly polyethylene (73.0 wt%). However, the catalytic behavior of the
      precatalyst can be adjusted by varying the MAO-to-Cr ratio. Thus, the use of 500
      equiv. causes a dramatic shift from polymerization to ethylene oligomerization,
      eventually producing mainly lighter alpha-olefin fractions [alpha-C4 (68.7 wt%)
      and alpha-C6 (19.2 wt%)]. A further increase in the amount of MAO (1000 equiv.)
      leads to a more balanced distribution of oligomers, with a drastic decrease in
      the alpha-C4 and increase in the alpha-C8 fractions. 

PMID- 26287599
TI  - Short-term Analysis vs Long-term Data on Total Hip Replacement Survivorship.

PMID- 26287600
TI  - The Future of AHRQ's Health Services Research.

PMID- 26287597
TI  - Phagocytosis of apoptotic cells in homeostasis.
AB  - Human bodies collectively turn over about 200 billion to 300 billion cells every
      day. Such turnover is an integral part of embryonic and postnatal development, as
      well as routine tissue homeostasis. This process involves the induction of
      programmed cell death in specific cells within the tissues and the specific
      recognition and removal of dying cells by a clearance 'crew' composed of
      professional, non-professional and specialized phagocytes. In the past few years,
      considerable progress has been made in identifying many features of apoptotic
      cell clearance. Some of these new observations challenge the way dying cells
      themselves are viewed, as well as how healthy cells interact with and respond to
      dying cells. Here we focus on the homeostatic removal of apoptotic cells in
      tissues. 

PMID- 26287601
TI  - NCOA1 promotes angiogenesis in breast tumors by simultaneously enhancing both
      HIF1alpha- and AP-1-mediated VEGFa transcription.
AB  - Nuclear receptor coactivator 1 (NCOA1) is overexpressed in a subset of breast
      cancer and its increased expression positively correlates with disease recurrence
      and metastasis. Although NCOA1 is known to promote breast cancer metastasis
      through working with multiple transcription factors to upregulate the expression
      of Twist1, ITGA5, CSF-1, SDF1 and CXCR4, the role of NCOA1 in breast tumor
      angiogenesis has not been investigated. In this study, we found that the
      microvascular density (MVD) was significantly decreased and increased in Ncoa1
      knockout and NCOA1-overexpressing mammary tumors, respectively, in several breast
      cancer mouse models. Knockout or knockdown of NCOA1 in breast cancer cell lines
      also markedly compromised their capability to induce angiogenesis in Matrigel
      plugs embedded subcutaneously in mice, while this compromised capability could be
      rescued by VEGFa treatment. At the molecular level, NCOA1 upregulates VEGFa
      expression in both mouse mammary tumors and cultured breast cancer cells, and it
      does so by associating with both c-Fos, which is recruited to the AP-1 site at bp
      -938 of the VEGFa promoter, and HIF1alpha, which is recruited to the HIF1alpha
      binding element at bp -979 of the VEGFa promoter, to enhance VEGFa transcription.
      In 140 human breast tumors, high NCOA1 protein correlates with high MVD and
      patients with both high NCOA1 and high MVD showed significantly shorter survival
      time. In summary, this study revealed a novel mechanism that NCOA1 potentiates
      breast cancer angiogenesis through upregulating HIF1alpha and AP-1-mediated VEGFa
      expression, which reinforces the rational of targeting NCOA1 in controlling
      breast cancer progression and metastasis. 

PMID- 26287602
TI  - miR-454 functions as an oncogene by inhibiting CHD5 in hepatocellular carcinoma.
AB  - Previous studies showed that miR-454 acted as an oncogene or tumor suppressor in
      cancer. However, its function in HCC remains unknown. In this study, we found
      that miR-454 expression was upregulated in HCC cell lines and tissues. Knockdown
      of miR-454 inhibited HCC cell proliferation and invasion and epithelial
      mesenchymal transition (EMT), whereas overexpression of miR-454 promoted HCC cell
      proliferation and invasion and EMT. Furthermore, we identified the CHD5 as a
      direct target of miR-454. CHD5 was downregulated in HCC tissues and cell lines
      and the expression level of CHD5 was inversely correlated with the expression of
      miR-454 in HCC tissues. In addition, knockdown of miR-454 inhibited the growth of
      HepG2-engrafted tumors in vivo. Taken together, these results indicated that miR
      454 functioned as an oncogene in HCC. 

PMID- 26287604
TI  - Immunodeficiency and CARD-BCL10-MALT1.

PMID- 26287603
TI  - Identification of miR-215 mediated targets/pathways via translational
      immunoprecipitation expression analysis (TrIP-chip).
AB  - Steady state mRNA expression profiling can identify the majority of miRNA
      targets. However, some translationally repressed miRNA targets are missed and
      thus not considered for functional validation. Therefore, analysis of mRNA
      translation can enhance miRNA target identification for functional studies. We
      have applied a unique approach to identify miRNA targets in a small number of
      cells. Actively translating mRNAs are associated with polyribosomes and newly
      synthesized peptide chains are associated with molecular chaperones such as
      HSP70s. Affinity capture beads were used to capture HSP70 chaperones associated
      with polyribosome complexes. The isolated actively translating mRNAs were used
      for high throughput expression profiling analysis. miR-215 is an important miRNA
      in colorectal cancer and loss of miR-215 is significantly associated with
      prognosis of this disease. miR-215 suppresses the expression of several key
      targets. We utilized the affinity capture approach to isolate miR-215 mediated
      mRNA target transcripts. This approach provides a unique way to identify targets
      regulated by non-coding RNAs and RNA binding proteins from a small number of
      cells. 

PMID- 26287606
TI  - Multiplex-PCR-Based Screening and Computational Modeling of Virulence Factors and
      T-Cell Mediated Immunity in Helicobacter pylori Infections for Accurate Clinical
      Diagnosis.
AB  - The outcome of H. pylori infection is closely related with bacteria's virulence
      factors and host immune response. The association between T cells and H. pylori
      infection has been identified, but the effects of the nine major H. pylori
      specific virulence factors; cagA, vacA, oipA, babA, hpaA, napA, dupA, ureA, ureB
      on T cell response in H. pylori infected patients have not been fully elucidated.
      We developed a multiplex- PCR assay to detect nine H. pylori virulence genes with
      in a three PCR reactions. Also, the expression levels of Th1, Th17 and Treg cell
      specific cytokines and transcription factors were detected by using qRT-PCR
      assays. Furthermore, a novel expert derived model is developed to identify set of
      factors and rules that can distinguish the ulcer patients from gastritis
      patients. Within all virulence factors that we tested, we identified a
      correlation between the presence of napA virulence gene and ulcer disease as a
      first data. Additionally, a positive correlation between the H. pylori dupA
      virulence factor and IFN-gamma, and H. pylori babA virulence factor and IL-17 was
      detected in gastritis and ulcer patients respectively. By using computer-based
      models, clinical outcomes of a patients infected with H. pylori can be predicted
      by screening the patient's H. pylori vacA m1/m2, ureA and cagA status and IFN
      gamma (Th1), IL-17 (Th17), and FOXP3 (Treg) expression levels. Herein, we report,
      for the first time, the relationship between H. pylori virulence factors and host
      immune responses for diagnostic prediction of gastric diseases using computer
      based models. 

PMID- 26287605
TI  - Anti-tumor effect of inhibition of IL-6 signaling in mucoepidermoid carcinoma.
AB  - Mucoepidermoid carcinoma (MEC) is the most frequent malignant salivary gland
      cancer. Response to chemoradiotherapy is modest, and therefore radical surgery
      remains the standard-of-care. Emerging evidence suggests that Interleukin (IL)-6
      signaling correlates with the survival of cancer stem cells and resistance to
      therapy. Here, we investigated whether inhibition of IL-6 receptor (IL-6R)
      signaling with tocilizumab (humanized anti-human IL-6R antibody) sensitizes MEC
      to chemotherapy using human mucoepidermoid carcinoma cell lines (UM-HMC) and
      correspondent xenograft models. In vitro, we observed that tocilizumab inhibited
      STAT3 phosphorylation but had no measurable effect in MEC cell viability (UM-HMC
      1,-3A,-3B). In contrast, the anti-tumor effect of single agent tocilizumab on MEC
      xenografts was comparable to paclitaxel or cisplatin. Combination of tocilizumab
      with cisplatin or paclitaxel enhanced the inhibitory effect of chemotherapy on
      xenograft growth (P < 0.05), time to failure (P < 0.01), decreased vascular
      endothelial growth factor (VEGF) expression and tumor microvessel density (P <
      0.05) without added systemic toxicities. Notably, tocilizumab decreased the
      fraction of MEC cancer stem cells (ALDH(high)CD44(high)) in vitro, and prevented
      paclitaxel-induced increase in the fraction of cancer stem cells in vivo (P <
      0.05). Collectively, these findings demonstrate that tocilizumab enhances the
      anti-tumor effect of conventional chemotherapy in preclinical models of
      mucoepidermoid carcinoma, and suggest that patients might benefit from
      combination therapy with an inhibitor of IL-6R signaling and chemotherapeutic
      agent such as paclitaxel.

PMID- 26287607
TI  - Polysomes of Trypanosoma brucei: Association with Initiation Factors and RNA
      Binding Proteins.
AB  - We report here the results of experiments designed to identify RNA-binding
      proteins that might be associated with Trypanosoma brucei polysomes. After some
      preliminary mass spectrometry of polysomal fractions, we investigated the
      distributions of selected tagged proteins using sucrose gradients and
      immunofluorescence. As expected, the polysomal fractions contained nearly all
      annotated ribosomal proteins, the translation-associated protein folding complex,
      and many translation factors, but also many other abundant proteins. Results
      suggested that cap-binding proteins EIF4E3 and EIF4E4 were associated with both
      free and membrane-bound polysomes. The EIF4E binding partners EIF4G4 and EIF4G3
      were present but the other EIF4E and EIF4G paralogues were not detected. The
      dominant EIF4E in the polysomal fraction is EIF4E4 and very few polysomal mRNAs
      are associated with EIF4G. Thirteen potential mRNA-binding proteins were detected
      in the polysomes, including the known polysome-associated protein RBP42. The
      locations of two of the other proteins were tested after epitope tagging: RBP29
      was in the nucleus and ZC3H29 was in the cytoplasm. Quantitative analyses showed
      that specific association of an RNA-binding protein with the polysome fraction in
      sucrose gradients will not be detected if the protein is in more than 25-fold
      molar excess over its target binding sites. 

PMID- 26287608
TI  - Perceptions of Workplace Heat Exposure and Controls among Occupational Hygienists
      and Relevant Specialists in Australia.
AB  - With warmer weather projections, workplace heat exposure is presenting a growing
      challenge to workers' health and safety. Occupational hygienists are the
      specialist group conducting measurements and providing advice on heat stress
      management to industry. In order to provide insights into hygienists perceptions
      on workplace heat exposure, current and future preparedness for extreme heat, and
      barriers to possible heat adaptation strategies, a self-administered
      questionnaire survey was conducted during a national conference of the Australian
      Institute of Occupational Hygienists. Nearly 90% of the 180 respondents were at
      least moderately concerned about extreme heat and 19% were dissatisfied with
      current heat stress prevention measures. Barriers recognized by the participants
      were lack of awareness (68%), insufficient training (56%), unsatisfactory
      management commitment (52%), and low compliance with prevention policies (40%).
      The findings suggest a need to refine occupational heat management and prevention
      strategies. 

PMID- 26287609
TI  - Outcome Prediction in Mathematical Models of Immune Response to Infection.
AB  - Clinicians need to predict patient outcomes with high accuracy as early as
      possible after disease inception. In this manuscript, we show that patient-to
      patient variability sets a fundamental limit on outcome prediction accuracy for a
      general class of mathematical models for the immune response to infection.
      However, accuracy can be increased at the expense of delayed prognosis. We
      investigate several systems of ordinary differential equations (ODEs) that model
      the host immune response to a pathogen load. Advantages of systems of ODEs for
      investigating the immune response to infection include the ability to collect
      data on large numbers of 'virtual patients', each with a given set of model
      parameters, and obtain many time points during the course of the infection. We
      implement patient-to-patient variability v in the ODE models by randomly
      selecting the model parameters from distributions with coefficients of variation
      v that are centered on physiological values. We use logistic regression with one
      versus-all classification to predict the discrete steady-state outcomes of the
      system. We find that the prediction algorithm achieves near 100% accuracy for v =
      0, and the accuracy decreases with increasing v for all ODE models studied. The
      fact that multiple steady-state outcomes can be obtained for a given initial
      condition, i.e. the basins of attraction overlap in the space of initial
      conditions, limits the prediction accuracy for v > 0. Increasing the elapsed time
      of the variables used to train and test the classifier, increases the prediction
      accuracy, while adding explicit external noise to the ODE models decreases the
      prediction accuracy. Our results quantify the competition between early prognosis
      and high prediction accuracy that is frequently encountered by clinicians. 

PMID- 26287610
TI  - Registrations of Assistance Dogs in California for Identification Tags: 1999
      2012.
AB  - Dogs are filling a growing number of roles supporting people with various
      disabilities, leading to a chaotic situation in the U.S. Although the federal
      laws allow public access with working dogs only for people with disabilities, no
      governmental enforcement or management system for such dogs exists. Furthermore,
      there is no substantive way to confirm whether the dog is an adequately trained
      assistance dog or not, as neither the handlers nor the dogs are required to carry
      any particular certification or identification. Therefore, unqualified assistance
      dogs and incidents such as dog bites by assistance dogs sometimes are problems in
      the U.S. A governmental oversight system could reduce problems, but no
      information is available about the current uses of assistance dogs in the U.S. We
      aimed to investigate the current demographics of registered assistance dogs and
      the evolving patterns in uses of dogs during 1999-2012 in California. We acquired
      data on assistance dogs registered by animal control facilities throughout
      California. We used descriptive statistics to describe the uses of these
      assistance dogs. The number of assistance dogs sharply increased, especially
      service dogs, in the past decade. Dogs with small body sizes, and new types of
      service dogs, such as service dogs for psychiatric and medical assistance,
      strongly contributed to the increase. The Assistance Dog Identification tags
      sometimes were mistakenly issued to dogs not fitting the definition of assistance
      dogs under the law, such as emotional support animals and some cats; this reveals
      errors in the California governmental registering system. Seemingly inappropriate
      dogs also were registered, such as those registered for the first time at older
      than 10 years of age. This study reveals a prevalence of misuse and
      misunderstanding of regulations and legislation on assistance dogs in California.

PMID- 26287611
TI  - Generation of Naive Bovine Induced Pluripotent Stem Cells Using PiggyBac
      Transposition of Doxycycline-Inducible Transcription Factors.
AB  - Generation of pluripotent stem cells (PSCs) in large domestic animals has
      achieved only limited success; most of the PSCs obtained to date have been
      classified as primed PSCs, which possess very little capacity to produce chimeric
      offspring. By contrast, mouse PSCs have been classified as naive PSCs that can
      contribute to most of the tissues of chimeras, including germ cells. Here, we
      describe the generation of two different types of bovine induced pluripotent stem
      cells (biPSCs) from amnion cells, achieved through introduction of piggyBac
      vectors containing doxycycline-inducible transcription factors (Oct3/4, Sox2,
      Klf4, and c-Myc). One type of biPSCs, cultured in medium supplemented with
      knockout serum replacement (KSR), FGF2, and bovine leukemia inhibitory factor
      (bLIF), had a flattened morphology like human PSCs; these were classified as
      primed-type. The other type biPSCs, cultured in KSR, bLIF, Mek/Erk inhibitor,
      GSK3 inhibitor and forskolin, had a compact morphology like mouse PSCs; these
      were classified as naive-type. Cells could easily be switched between these two
      types of biPSCs by changing the culture conditions. Both types of biPSCs had
      strong alkaline phosphatase activity, expressed pluripotent markers (OCT3/4,
      NANOG, REX1, ESRRbeta, STELLA, and SOCS3), and formed embryoid bodies that gave
      rise to differentiated cells from all three embryonic germ layers. However, only
      naive-type biPSCs showed the hallmarks of naive mouse PSCs, such as LIF-dependent
      proliferation, lack of FGF5 expression, and active XIST expression with two
      active X chromosomes. Furthermore, naive-type biPSCs could contribute to the
      inner cell mass (ICM) of host blastocysts and most tissues within chimeric
      embryos. This is the first report of generation of biPSCs with several
      characteristics similar to those of naive mouse PSCs and a demonstrated potential
      to contribute to chimeras. 

PMID- 26287612
TI  - Aerosolization of a Human Norovirus Surrogate, Bacteriophage MS2, during
      Simulated Vomiting.
AB  - Human noroviruses (NoV) are the leading cause of acute gastroenteritis worldwide.
      Epidemiological studies of outbreaks have suggested that vomiting facilitates
      transmission of human NoV, but there have been no laboratory-based studies
      characterizing the degree of NoV release during a vomiting event. The purpose of
      this work was to demonstrate that virus aerosolization occurs in a simulated
      vomiting event, and to estimate the amount of virus that is released in those
      aerosols. A simulated vomiting device was constructed at one-quarter scale of the
      human body following similitude principles. Simulated vomitus matrices at low
      (6.24 mPa*s) and high (177.5 mPa*s) viscosities were inoculated with low (108
      PFU/mL) and high (1010 PFU/mL) concentrations of bacteriophage MS2 and placed in
      the artificial "stomach" of the device, which was then subjected to scaled
      physiologically relevant pressures associated with vomiting. Bio aerosols were
      captured using an SKC Biosampler. In low viscosity artificial vomitus, there were
      notable differences between recovered aerosolized MS2 as a function of pressure
      (i.e., greater aerosolization with increased pressure), although this was not
      always statistically significant. This relationship disappeared when using high
      viscosity simulated vomitus. The amount of MS2 aerosolized as a percent of total
      virus "vomited" ranged from 7.2 x 10-5 to 2.67 x 10-2 (which corresponded to a
      range of 36 to 13,350 PFU total). To our knowledge, this is the first study to
      document and measure aerosolization of a NoV surrogate in a similitude-based
      physical model. This has implications for better understanding the transmission
      dynamics of human NoV and for risk modeling purposes, both of which can help in
      designing effective infection control measures. 

PMID- 26287614
TI  - The Spectrum of alpha-Thalassemia Mutations in Kermanshah Province, West Iran.
AB  - Thalassemia is a hereditary blood disorder that results from genetic defects
      causing deficient synthesis of hemoglobin (Hb) polypeptide chains. Although
      thalassemia mostly affects developing countries, there is limited knowledge of
      its accurate frequency and distribution in these regions. Knowing the prevalence
      of thalassemia and the frequency of responsible mutations is therefore an
      important step in the prevention and control program as well as treatment
      strategies. alpha-Thalassemia (alpha-thal) is prevalent in Middle East Asian
      populations, including Iran. In this study, 678 unrelated alpha-thal carriers,
      attending the Kermanshah Medical Genetics Laboratory, Kermanshah, Iran, were
      investigated for alpha-globin gene mutations by multiplex polymerase chain
      reaction (PCR) and direct sequencing. The most common mutation among our patients
      was -alpha(3.7) (rightward) (60.9%) deletion, which is also known to occur in
      high frequencies in other parts of Iran, in Southeast Asia and Mediterranean
      countries. Other prevalent alpha-thal mutations were alpha(-5 nt) (10.6%),
      alpha(polyA4) (9.9%), alpha(polyA6) (3.7%), - -(MED) (3.2%), -alpha(4.2)
      (leftward) (3.1%) deletion and codon 59 (Hb Adana; HBA1: c.179 G > A) (2.5%).
      These comprehensive new data are useful for establishing a screening strategy for
      the effective control of alpha-thal in Kermanshah Province. 

PMID- 26287613
TI  - A Multi-Area Stochastic Model for a Covert Visual Search Task.
AB  - Decisions typically comprise several elements. For example, attention must be
      directed towards specific objects, their identities recognized, and a choice made
      among alternatives. Pairs of competing accumulators and drift-diffusion processes
      provide good models of evidence integration in two-alternative perceptual
      choices, but more complex tasks requiring the coordination of attention and
      decision making involve multistage processing and multiple brain areas. Here we
      consider a task in which a target is located among distractors and its identity
      reported by lever release. The data comprise reaction times, accuracies, and
      single unit recordings from two monkeys' lateral interparietal area (LIP)
      neurons. LIP firing rates distinguish between targets and distractors, exhibit
      stimulus set size effects, and show response-hemifield congruence effects. These
      data motivate our model, which uses coupled sets of leaky competing accumulators
      to represent processes hypothesized to occur in feature-selective areas and limb
      motor and pre-motor areas, together with the visual selection process occurring
      in LIP. Model simulations capture the electrophysiological and behavioral data,
      and fitted parameters suggest that different connection weights between LIP and
      the other cortical areas may account for the observed behavioral differences
      between the animals. 

PMID- 26287615
TI  - Aquaporin 1 Is Involved in Acid Secretion by Ionocytes of Zebrafish Embryos
      through Facilitating CO2 Transport.
AB  - Mammalian aquaporin 1 (AQP1) is well known to function as a membrane channel for
      H2O and CO2 transport. Zebrafish AQP1a.1 (the homologue of mammalian AQP1) was
      recently identified in ionocytes of embryos; however its role in ionocytes is
      still unclear. In this study, we hypothesized that zebrafish AQP1a.1 is involved
      in the acid secretion by ionocytes through facilitating H2O and CO2 diffusion. A
      real-time PCR showed that mRNA levels of AQP1a.1 in embryos were induced by
      exposure to 1% CO2 hypercapnia for 3 days. In situ hybridization and
      immunohistochemistry showed that the AQP1a.1 transcript was highly expressed by
      acid-secreting ionocytes, i.e., H+-ATPase-rich (HR) cells. A scanning ion
      selective electrode technique (SIET) was applied to analyze CO2-induced H+
      secretion by individual ionocytes in embryos. H+ secretion by HR cells remarkably
      increased after a transient loading of CO2 (1% for 10 min). AQP1a.1 knockdown
      with morpholino oligonucleotides decreased the H+ secretion of HR cells by about
      half and limited the CO2 stimulated increase. In addition, exposure to an AQP
      inhibitor (PCMB) for 10 min also suppressed CO2-induced H+ secretion. Results
      from this study support our hypothesis and provide in vivo evidence of the
      physiological role of AQP1 in CO2 transport. 

PMID- 26287617
TI  - SpIDA Surveys the Intricate Web of Macromolecular Oligomerization In Situ.

PMID- 26287616
TI  - Concentration, Size Distribution, and Infectivity of Airborne Particles Carrying
      Swine Viruses.
AB  - When pathogens become airborne, they travel associated with particles of
      different size and composition. Particle size determines the distance across
      which pathogens can be transported, as well as the site of deposition and the
      survivability of the pathogen. Despite the importance of this information, the
      size distribution of particles bearing viruses emitted by infectious animals
      remains unknown. In this study we characterized the concentration and size
      distribution of inhalable particles that transport influenza A virus (IAV),
      porcine reproductive and respiratory syndrome virus (PRRSV), and porcine epidemic
      diarrhea virus (PEDV) generated by acutely infected pigs and assessed virus
      viability for each particle size range. Aerosols from experimentally infected
      pigs were sampled for 24 days using an Andersen cascade impactor able to separate
      particles by size (ranging from 0.4 to 10 micrometer (MUm) in diameter). Air
      samples collected for the first 9, 20 and the last 3 days of the study were
      analyzed for IAV, PRRSV and PEDV, respectively, using quantitative reverse
      transcription polymerase chain reaction (RT-PCR) and quantified as geometric mean
      copies/m(3) within each size range. IAV was detected in all particle size ranges
      in quantities ranging from 5.5x10(2) (in particles ranging from 1.1 to 2.1 MUm)
      to 4.3x10(5) RNA copies/m(3) in the largest particles (9.0-10.0 MUm). PRRSV was
      detected in all size ranges except particles between 0.7 and 2.1 MUm in
      quantities ranging from 6x10(2) (0.4-0.7 MUm) to 5.1x10(4) RNA copies/m(3) (9.0
      10.0 MUm). PEDV, an enteric virus, was detected in all particle sizes and in
      higher quantities than IAV and PRRSV (p < 0.0001) ranging from 1.3x10(6) (0.4-0.7
      MUm) to 3.5x10(8) RNA copies/m(3) (9.0-10.0 MUm). Infectious status was
      demonstrated for the 3 viruses, and in the case of IAV and PRRSV, viruses were
      isolated from particles larger than 2.1 MUm. In summary, our results indicated
      that airborne PEDV, IAV and PRRSV can be found in a wide range of particle sizes.
      However, virus viability is particle size dependent.

PMID- 26287618
TI  - Through Thick and Thin--Interfilament Communication in Muscle.

PMID- 26287619
TI  - Better Together: Lipopeptide Micelle Formation Enhances Antimicrobial
      Selectivity.

PMID- 26287620
TI  - Moving Cell Boundaries Drive Nuclear Shaping during Cell Spreading.
AB  - The nucleus has a smooth, regular appearance in normal cells, and its shape is
      greatly altered in human pathologies. Yet, how the cell establishes nuclear shape
      is not well understood. We imaged the dynamics of nuclear shaping in NIH3T3
      fibroblasts. Nuclei translated toward the substratum and began flattening during
      the early stages of cell spreading. Initially, nuclear height and width
      correlated with the degree of cell spreading, but over time, reached steady-state
      values even as the cell continued to spread. Actomyosin activity, actomyosin
      bundles, microtubules, and intermediate filaments, as well as the LINC complex,
      were all dispensable for nuclear flattening as long as the cell could spread.
      Inhibition of actin polymerization as well as myosin light chain kinase with the
      drug ML7 limited both the initial spreading of cells and flattening of nuclei,
      and for well-spread cells, inhibition of myosin-II ATPase with the drug
      blebbistatin decreased cell spreading with associated nuclear rounding. Together,
      these results show that cell spreading is necessary and sufficient to drive
      nuclear flattening under a wide range of conditions, including in the presence or
      absence of myosin activity. To explain this observation, we propose a
      computational model for nuclear and cell mechanics that shows how frictional
      transmission of stress from the moving cell boundaries to the nuclear surface
      shapes the nucleus during early cell spreading. Our results point to a
      surprisingly simple mechanical system in cells for establishing nuclear shapes. 

PMID- 26287621
TI  - Feeling for Filaments: Quantification of the Cortical Actin Web in Live Vascular
      Endothelium.
AB  - Contact-mode atomic force microscopy (AFM) has been shown to reveal cortical
      actin structures. Using live endothelial cells, we visualized cortical actin
      dynamics simultaneously by AFM and confocal fluorescence microscopy. We present a
      method that quantifies dynamic changes in the mechanical ultrastructure of the
      cortical actin web. We argue that the commonly used, so-called error signal
      imaging in AFM allows a qualitative, but not quantitative, analysis of cortical
      actin dynamics. The approach we used comprises fast force-curve-based topography
      imaging and subsequent image processing that enhances local height differences.
      Dynamic changes in the organization of the cytoskeleton network can be observed
      and quantified by surface roughness calculations and automated morphometrics.
      Upon treatment with low concentrations of the actin-destabilizing agent
      cytochalasin D, the cortical cytoskeleton network is thinned out and the average
      mesh size increases. In contrast, jasplakinolide, a drug that enhances actin
      polymerization, consolidates the cytoskeleton network and reduces the average
      mesh area. In conclusion, cortical actin dynamics can be quantified in live
      cells. To our knowledge, this opens a new pathway for conducting quantitative
      structure-function analyses of the endothelial actin web just beneath the apical
      plasma membrane. 

PMID- 26287622
TI  - Protrusive and Contractile Forces of Spreading Human Neutrophils.
AB  - Human neutrophils are mediators of innate immunity and undergo dramatic shape
      changes at all stages of their functional life cycle. In this work, we quantified
      the forces associated with a neutrophil's morphological transition from a
      nonadherent, quiescent sphere to its adherent and spread state. We did this by
      tracking, with high spatial and temporal resolution, the cell's mechanical
      behavior during spreading on microfabricated post-array detectors printed with
      the extracellular matrix protein fibronectin. Two dominant mechanical regimes
      were observed: transient protrusion and steady-state contraction. During
      spreading, a wave of protrusive force (75 +/- 8 pN/post) propagates radially
      outward from the cell center at a speed of 206 +/- 28 nm/s. Once completed, the
      cells enter a sustained contractile state. Although post engagement during
      contraction was continuously varying, posts within the core of the contact zone
      were less contractile (-20 +/- 10 pN/post) than those residing at the geometric
      perimeter (-106 +/- 10 pN/post). The magnitude of the protrusive force was found
      to be unchanged in response to cytoskeletal inhibitors of lamellipodium formation
      and myosin II-mediated contractility. However, cytochalasin B, known to reduce
      cortical tension in neutrophils, slowed spreading velocity (61 +/- 37 nm/s)
      without significantly reducing protrusive force. Relaxation of the actin cortical
      shell was a prerequisite for spreading on post arrays as demonstrated by
      stiffening in response to jasplakinolide and the abrogation of spreading. ROCK
      and myosin II inhibition reduced long-term contractility. Function blocking
      antibody studies revealed haptokinetic spreading was induced by beta2 integrin
      ligation. Neutrophils were found to moderately invaginate the post arrays to a
      depth of ~1 MUm as measured from spinning disk confocal microscopy. Our work
      suggests a competition of adhesion energy, cortical tension, and the relaxation
      of cortical tension is at play at the onset of neutrophil spreading. 

PMID- 26287623
TI  - Spatial Intensity Distribution Analysis Reveals Abnormal Oligomerization of
      Proteins in Single Cells.
AB  - Knowledge of membrane receptor organization is essential for understanding the
      initial steps in cell signaling and trafficking mechanisms, but quantitative
      analysis of receptor interactions at the single-cell level and in different
      cellular compartments has remained highly challenging. To achieve this, we apply
      a quantitative image analysis technique-spatial intensity distribution analysis
      (SpIDA)-that can measure fluorescent particle concentrations and oligomerization
      states within different subcellular compartments in live cells. An important
      technical challenge faced by fluorescence microscopy-based measurement of
      oligomerization is the fidelity of receptor labeling. In practice, imperfect
      labeling biases the distribution of oligomeric states measured within an
      aggregated system. We extend SpIDA to enable analysis of high-order oligomers
      from fluorescence microscopy images, by including a probability weighted
      correction algorithm for nonemitting labels. We demonstrated that this fraction
      of nonemitting probes could be estimated in single cells using SpIDA measurements
      on model systems with known oligomerization state. Previously, this artifact was
      measured using single-step photobleaching. This approach was validated using
      computer-simulated data and the imperfect labeling was quantified in cells with
      ion channels of known oligomer subunit count. It was then applied to quantify the
      oligomerization states in different cell compartments of the proteolipid protein
      (PLP) expressed in COS-7 cells. Expression of a mutant PLP linked to impaired
      trafficking resulted in the detection of PLP tetramers that persist in the
      endoplasmic reticulum, while no difference was measured at the membrane between
      the distributions of wild-type and mutated PLPs. Our results demonstrate that
      SpIDA allows measurement of protein oligomerization in different compartments of
      intact cells, even when fractional mislabeling occurs as well as photobleaching
      during the imaging process, and reveals insights into the mechanism underlying
      impaired trafficking of PLP. 

PMID- 26287624
TI  - Anionic Lipids Modulate the Activity of the Aquaglyceroporin GlpF.
AB  - The structure and composition of a biological membrane can severely influence the
      activity of membrane-embedded proteins. Here, we show that the E. coli
      aquaglyceroporin GlpF has only little activity in lipid bilayers formed from
      native E. coli lipids. Thus, at first glance, GlpF appears to not be optimized
      for its natural membrane environment. In fact, we found that GlpF activity was
      severely affected by negatively charged lipids regardless of the exact chemical
      nature of the lipid headgroup, whereas GlpF was not sensitive to changes in the
      lateral membrane pressure. These observations illustrate a potential mechanism by
      which the activity of an alpha-helical membrane protein is modulated by the
      negative charge density around the protein. 

PMID- 26287625
TI  - Two-Point Microrheology of Phase-Separated Domains in Lipid Bilayers.
AB  - Though the importance of membrane fluidity for cellular function has been well
      established for decades, methods for measuring lipid bilayer viscosity remain
      challenging to devise and implement. Recently, approaches based on characterizing
      the Brownian dynamics of individual tracers such as colloidal particles or lipid
      domains have provided insights into bilayer viscosity. For fluids in general,
      however, methods based on single-particle trajectories provide a limited view of
      hydrodynamic response. The technique of two-point microrheology, in which
      correlations between the Brownian dynamics of pairs of tracers report on the
      properties of the intervening medium, characterizes viscosity at length-scales
      that are larger than that of individual tracers and has less sensitivity to
      tracer-induced distortions, but has never been applied to lipid membranes. We
      present, to our knowledge, the first two-point microrheological study of lipid
      bilayers, examining the correlated motion of domains in phase-separated lipid
      vesicles and comparing one- and two-point results. We measure two-point
      correlation functions in excellent agreement with the forms predicted by two
      dimensional hydrodynamic models, analysis of which reveals a viscosity
      intermediate between those of the two lipid phases, indicative of global fluid
      properties rather than the viscosity of the local neighborhood of the tracer. 

PMID- 26287626
TI  - Hydrophobic Mismatch Drives the Interaction of E5 with the Transmembrane Segment
      of PDGF Receptor.
AB  - The oncogenic E5 protein from bovine papillomavirus is a short (44 amino acids
      long) integral membrane protein that forms homodimers. It activates platelet
      derived growth factor receptor (PDGFR) beta in a ligand-independent manner by
      transmembrane helix-helix interactions. The nature of this recognition event
      remains elusive, as numerous mutations are tolerated in the E5 transmembrane
      segment, with the exception of one hydrogen-bonding residue. Here, we examined
      the conformation, stability, and alignment of the E5 protein in fluid lipid
      membranes of substantially varying bilayer thickness, in both the absence and
      presence of the PDGFR transmembrane segment. Quantitative synchrotron radiation
      circular dichroism analysis revealed a very long transmembrane helix for E5 of
      ~26 amino acids. Oriented circular dichroism and solid-state (15)N-NMR showed
      that the alignment and stability of this unusually long segment depend critically
      on the membrane thickness. When reconstituted alone in exceptionally thick DNPC
      lipid bilayers, the E5 helix was found to be inserted almost upright. In
      moderately thick bilayers (DErPC and DEiPC), it started to tilt and became
      slightly deformed, and finally it became aggregated in conventional DOPC, POPC,
      and DMPC membranes due to hydrophobic mismatch. On the other hand, when E5 was co
      reconstituted with the transmembrane segment of PDGFR, it was able to tolerate
      even the most pronounced mismatch and was stabilized by binding to the receptor,
      which has the same hydrophobic length. As E5 is known to activate PDGFR within
      the thin membranes of the Golgi compartment, we suggest that the intrinsic
      hydrophobic mismatch of these two interaction partners drives them together. They
      seem to recognize each other by forming a closely packed bundle of mutually
      aligned transmembrane helices, which is further stabilized by a specific pair of
      hydrogen-bonding residues. 

PMID- 26287627
TI  - Thermodynamics of Micelle Formation and Membrane Fusion Modulate Antimicrobial
      Lipopeptide Activity.
AB  - Antimicrobial lipopeptides (AMLPs) are antimicrobial drug candidates that
      preferentially target microbial membranes. One class of AMLPs, composed of
      cationic tetrapeptides attached to an acyl chain, have minimal inhibitory
      concentrations in the micromolar range against a range of bacteria and fungi.
      Previously, we used coarse-grained molecular dynamics simulations and free energy
      methods to study the thermodynamics of their interaction with membranes in their
      monomeric state. Here, we extended the study to the biologically relevant
      micellar state, using, to our knowledge, a novel reaction coordinate based on
      hydrophobic contacts. Using umbrella sampling along this reaction coordinate, we
      identified the critical transition states when micelles insert into membranes.
      The results indicate that the binding of these AMLP micelles to membranes is
      thermodynamically favorable, but in contrast to the monomeric case, there are
      significant free energy barriers. The height of these free energy barriers
      depends on the membrane composition, suggesting that the AMLPs' ability to
      selectively target bacterial membranes may be as much kinetic as thermodynamic.
      This mechanism highlights the importance of considering oligomeric state in
      solution as criterion when optimizing peptides or lipopeptides as antibiotic
      leads. 

PMID- 26287628
TI  - Synaptobrevin Transmembrane Domain Dimerization Studied by Multiscale Molecular
      Dynamics Simulations.
AB  - Synaptic vesicle fusion requires assembly of the SNARE complex composed of SNAP
      25, syntaxin-1, and synaptobrevin-2 (sybII) proteins. The SNARE proteins found in
      vesicle membranes have previously been shown to dimerize via transmembrane (TM)
      domain interactions. While syntaxin homodimerization is supposed to promote the
      transition from hemifusion to complete fusion, the role of synaptobrevin's TM
      domain association in the fusion process remains poorly understood. Here, we
      combined coarse-grained and atomistic simulations to model the homodimerization
      of the sybII transmembrane domain and of selected TM mutants. The wild-type helix
      is shown to form a stable, right-handed dimer with the most populated helix-helix
      interface, including key residues predicted in a previous mutagenesis study. In
      addition, two alternative binding interfaces were discovered, which are essential
      to explain the experimentally observed higher-order oligomerization of sybII. In
      contrast, only one dimerization interface was found for a fusion-inactive poly
      Leu mutant. Moreover, the association kinetics found for this mutant is lower as
      compared to the wild-type. These differences in dimerization between the wild
      type and the poly-Leu mutant are suggested to be responsible for the reported
      differences in fusogenic activity between these peptides. This study provides
      molecular insight into the role of TM sequence specificity for peptide
      aggregation in membranes. 

PMID- 26287629
TI  - NMR Dynamics of Transmembrane and Intracellular Domains of p75NTR in Lipid
      Protein Nanodiscs.
AB  - P75NTR is a type I integral membrane protein that plays a key role in
      neurotrophin signaling. However, structural data for the receptor in various
      functional states are sparse and controversial. In this work, we studied the
      spatial structure and mobility of the transmembrane and intracellular parts of
      p75NTR, incorporated into lipid-protein nanodiscs of various sizes and
      compositions, by solution NMR spectroscopy. Our data reveal a high level of
      flexibility and disorder in the juxtamembrane chopper domain of p75NTR, which
      results in the motions of the receptor death domain being uncoupled from the
      motions of the transmembrane helix. Moreover, none of the intracellular domains
      of p75NTR demonstrated a propensity to interact with the membrane or to self
      associate under the experimental conditions. The obtained data are discussed in
      the context of the receptor activation mechanism. 

PMID- 26287630
TI  - The Conformation of Myosin Heads in Relaxed Skeletal Muscle: Implications for
      Myosin-Based Regulation.
AB  - In isolated thick filaments from many types of muscle, the two head domains of
      each myosin molecule are folded back against the filament backbone in a
      conformation called the interacting heads motif (IHM) in which actin interaction
      is inhibited. This conformation is present in resting skeletal muscle, but it is
      not known how exit from the IHM state is achieved during muscle activation. Here,
      we investigated this by measuring the in situ conformation of the light chain
      domain of the myosin heads in relaxed demembranated fibers from rabbit psoas
      muscle using fluorescence polarization from bifunctional rhodamine probes at four
      sites on the C-terminal lobe of the myosin regulatory light chain (RLC). The
      order parameter <P2> describing probe orientation with respect to the filament
      axis had a roughly sigmoidal dependence on temperature in relaxing conditions,
      with a half-maximal change at ~19 degrees C. Either lattice compression by 5%
      dextran T500 or addition of 25 MUM blebbistatin decreased the transition
      temperature to ~14 degrees C. Maximum entropy analysis revealed three preferred
      orientations of the myosin RLC region at 25 degrees C and above, two with its
      long axis roughly parallel to the filament axis and one roughly perpendicular.
      The parallel orientations are similar to those of the so-called blocked and free
      heads in the IHM and are stabilized by either lattice compression or
      blebbistatin. In relaxed skeletal muscle at near-physiological temperature and
      myofilament lattice spacing, the majority of the myosin heads have their light
      chain domains in IHM-like conformations, with a minority in a distinct
      conformation with their RLC regions roughly perpendicular to the filament axis.
      None of these three orientation populations were present during active
      contraction. These results are consistent with a regulatory transition of the
      thick filament in skeletal muscle associated with a conformational equilibrium of
      the myosin heads. 

PMID- 26287631
TI  - Prion Protein-Antibody Complexes Characterized by Chromatography-Coupled Small
      Angle X-Ray Scattering.
AB  - Aberrant self-assembly, induced by structural misfolding of the prion proteins,
      leads to a number of neurodegenerative disorders. In particular, misfolding of
      the mostly alpha-helical cellular prion protein (PrP(C)) into a beta-sheet-rich
      disease-causing isoform (PrP(Sc)) is the key molecular event in the formation of
      PrP(Sc) aggregates. The molecular mechanisms underlying the PrP(C)-to-PrP(Sc)
      conversion and subsequent aggregation remain to be elucidated. However, in
      persistently prion-infected cell-culture models, it was shown that treatment with
      monoclonal antibodies against defined regions of the prion protein (PrP) led to
      the clearing of PrP(Sc) in cultured cells. To gain more insight into this
      process, we characterized PrP-antibody complexes in solution using a fast protein
      liquid chromatography coupled with small-angle x-ray scattering (FPLC-SAXS)
      procedure. High-quality SAXS data were collected for full-length recombinant
      mouse PrP [denoted recPrP(23-230)] and N-terminally truncated recPrP(89-230), as
      well as their complexes with each of two Fab fragments (HuM-P and HuM-R1), which
      recognize N- and C-terminal epitopes of PrP, respectively. In-line measurements
      by fast protein liquid chromatography coupled with SAXS minimized data artifacts
      caused by a non-monodispersed sample, allowing structural analysis of PrP alone
      and in complex with Fab antibodies. The resulting structural models suggest two
      mechanisms for how these Fabs may prevent the conversion of PrP(C) into PrP(Sc). 

PMID- 26287632
TI  - Protein Conformational Changes Are Detected and Resolved Site Specifically by
      Second-Harmonic Generation.
AB  - We present here a straightforward, broadly applicable technique for real-time
      detection and measurement of protein conformational changes in solution. This
      method is based on tethering proteins labeled with a second-harmonic generation
      (SHG) active dye to supported lipid bilayers. We demonstrate our method by
      measuring the conformational changes that occur upon ligand binding with three
      well-characterized proteins labeled at lysine residues: calmodulin (CaM), maltose
      binding protein (MBP), and dihydrofolate reductase (DHFR). We also create a
      single-site cysteine mutant of DHFR engineered within the Met20 catalytic loop
      region and study the protein's structural motion at this site. Using published x
      ray crystal structures, we show that the changes in the SHG signals upon ligand
      binding are the result of structural motions that occur at the labeled sites
      between the apo and ligand-bound forms of the proteins, which are easily
      distinguished from each other. In addition, we demonstrate that different
      magnitudes of the SHG signal changes are due to different and specific ligand
      induced conformational changes. Taken together, these data illustrate the
      potential of the SHG approach for detecting and measuring protein conformational
      changes for a wide range of biological applications. 

PMID- 26287633
TI  - Dead-End Elimination with a Polarizable Force Field Repacks PCNA Structures.
AB  - A balance of van der Waals, electrostatic, and hydrophobic forces drive the
      folding and packing of protein side chains. Although such interactions between
      residues are often approximated as being pairwise additive, in reality, higher
      order many-body contributions that depend on environment drive hydrophobic
      collapse and cooperative electrostatics. Beginning from dead-end elimination, we
      derive the first algorithm, to our knowledge, capable of deterministic global
      repacking of side chains compatible with many-body energy functions. The approach
      is applied to seven PCNA x-ray crystallographic data sets with resolutions 2.5
      3.8 A (mean 3.0 A) using an open-source software. While PDB_REDO models average
      an Rfree value of 29.5% and MOLPROBITY score of 2.71 A (77th percentile), dead
      end elimination with the polarizable AMOEBA force field lowered Rfree by 2.8
      26.7% and improved mean MOLPROBITY score to atomic resolution at 1.25 A (100th
      percentile). For structural biology applications that depend on side-chain
      repacking, including x-ray refinement, homology modeling, and protein design, the
      accuracy limitations of pairwise additivity can now be eliminated via polarizable
      or quantum mechanical potentials. 

PMID- 26287634
TI  - Variable-Field Analytical Ultracentrifugation: I. Time-Optimized Sedimentation
      Equilibrium.
AB  - Sedimentation equilibrium (SE) analytical ultracentrifugation (AUC) is a gold
      standard for the rigorous determination of macromolecular buoyant molar masses
      and the thermodynamic study of reversible interactions in solution. A significant
      experimental drawback is the long time required to attain SE, which is usually on
      the order of days. We have developed a method for time-optimized SE (toSE) with
      defined time-varying centrifugal fields that allow SE to be attained in a
      significantly (up to 10-fold) shorter time than is usually required. To achieve
      this, numerical Lamm equation solutions for sedimentation in time-varying fields
      are computed based on initial estimates of macromolecular transport properties. A
      parameterized rotor-speed schedule is optimized with the goal of achieving a
      minimal time to equilibrium while limiting transient sample preconcentration at
      the base of the solution column. The resulting rotor-speed schedule may include
      multiple over- and underspeeding phases, balancing the formation of gradients
      from strong sedimentation fluxes with periods of high diffusional transport. The
      computation is carried out in a new software program called TOSE, which also
      facilitates convenient experimental implementation. Further, we extend AUC data
      analysis to sedimentation processes in such time-varying centrifugal fields. Due
      to the initially high centrifugal fields in toSE and the resulting strong
      migration, it is possible to extract sedimentation coefficient distributions from
      the early data. This can provide better estimates of the size of macromolecular
      complexes and report on sample homogeneity early on, which may be used to further
      refine the prediction of the rotor-speed schedule. In this manner, the toSE
      experiment can be adapted in real time to the system under study, maximizing both
      the information content and the time efficiency of SE experiments. 

PMID- 26287636
TI  - Toxin Profile, Biofilm Formation, and Molecular Characterization of Emetic Toxin
      Producing Bacillus cereus Group Isolates from Human Stools.
AB  - Emetic toxin-producing Bacillus cereus group species are an important problem,
      because the staple food for Korean is grains such as rice. In this study, we
      determined the prevalence (24 of 129 isolates) of emetic B. cereus in 36,745
      stool samples from sporadic food-poisoning cases in Korea between 2007 and 2008.
      The toxin gene profile, toxin production, and biofilm-forming ability of the
      emetic B. cereus isolates were investigated. Repetitive element sequence
      polymorphism polymerase chain reaction fingerprints (rep-PCR) were also used to
      assess the intraspecific biodiversity of these isolates. Emetic B. cereus was
      present in 0.07% of the sporadic food-poisoning cases. The 24 emetic isolates
      identified all carried the nheABC and entFM genes and produced NHE enterotoxin.
      However, they did not have hemolysin BL toxin or related genes. A relationship
      between biofilm formation and toxin production was not observed in this study.
      The rep-PCR fingerprints of the B. cereus isolates were not influenced by the
      presence of toxin genes, or biofilm-forming ability. The rep-PCR assay
      discriminated emetic B. cereus isolates from nonemetic isolates, even if this
      assay did not perfectly discriminate these isolates. Further study on emetic
      isolates possessing a high degree of diversity may be necessary to evaluate the
      performance of the subtyping assay to discriminate emetic and nonemetic B. cereus
      isolates and could provide a more accurate indication of the risk from B. cereus
      strains. 

PMID- 26287635
TI  - Mechanistic Investigation of the Arrhythmogenic Role of Oxidized CaMKII in the
      Heart.
AB  - Oxidative stress and calcium (Ca(2+))/calmodulin (CaM)-dependent protein kinase
      II (CaMKII) both play important roles in the pathogenesis of cardiac disease.
      Although the pathophysiological relevance of reactive oxygen species (ROS) and
      CaMKII has been appreciated for some time, recent work has shown that ROS can
      directly oxidize CaMKII, leading to its persistent activity and an increase of
      the likelihood of cellular arrhythmias such as early afterdepolarizations (EADs).
      Because CaMKII modulates the function of many proteins involved in excitation
      contraction coupling, elucidation of its role in cardiac function, in both
      healthy and oxidative stress conditions, is challenging. To investigate this
      role, we have developed a model of CaMKII activation that includes both the
      phosphorylation-dependent and the newly identified oxidation-dependent activation
      pathways. This model is incorporated into our previous local-control model of the
      cardiac myocyte that describes excitation-contraction coupling via stochastic
      simulation of individual Ca(2+) release units and CaMKII-mediated phosphorylation
      of L-type Ca(2+) channels (LCCs), ryanodine receptors and sodium (Na(+))
      channels. The model predicts the experimentally measured slow-rate dependence of
      H2O2-induced EADs. Upon increased H2O2, simulations suggest that selective
      activation of late Na(+) current (INaL), although it prolongs action potential
      duration, is not by itself sufficient to produce EADs. Similar results are
      obtained if CaMKII effects on LCCs and ryanodine receptors are considered
      separately. However, EADs emerge upon simultaneous activation of both LCCs and
      Na(+) channels. Further modeling results implicate activation of the Na(+)-Ca(2+)
      exchanger (NCX) as an important player in the generation of EADs. During
      bradycardia, the emergence of H2O2-induced EADs was correlated with a shift in
      the timing of NCX current reversal toward the plateau phase earlier in the action
      potential. Using the timing of NCX current reversal as an indicator event for
      EADs, the model identified counterintuitive ionic changes-difficult to
      experimentally dissect-that have the greatest influence on ROS-related arrhythmia
      propensity. 

PMID- 26287637
TI  - Dairy products and inflammation: A review of the clinical evidence.
AB  - Inflammation is a major biological process regulating the interaction between
      organisms and the environment, including the diet. Because of the increase in
      chronic inflammatory diseases, and in light of the immune-regulatory properties
      of breastfeeding, the ability of dairy products to modulate inflammatory
      processes in humans is an important but unresolved issue. Here, we report a
      systematic review of 52 clinical trials investigating inflammatory markers in
      relation to the consumption of dairy products. An inflammatory score (IS) was
      defined to quantitatively evaluate this interaction. The IS was significantly
      positive for the entire data set, indicating an anti-inflammatory activity in
      humans. When the subjects were stratified according to their health status, the
      IS was strongly indicative of an anti-inflammatory activity in subjects with
      metabolic disorders and of a pro-inflammatory activity in subjects allergic to
      bovine milk. Stratifying the data by product categories associated both low-fat
      and high-fat products, as well as fermented products, with an anti-inflammatory
      activity. Remarkably, the literature is characterized by a large gap in knowledge
      on bioavailability of bioactive nutrients. Future research should thus better
      combine food and nutritional sciences to adequately follow the fate of these
      nutrients along the gastrointestinal and metabolic axes.

PMID- 26287638
TI  - [Correlation of Phonological STM-Performances with Language-Based Dimensions in
      Children with APD].
AB  - OBJECTIVE: Phonological short-term memory (PSTM) is a functional component in
      language processing. This study investigated the association between some
      language-based dimensions of an eclectic test battery for auditory processing
      disorders (APD) and test performance in PSTM (recall for digits, sentences; non
      word repetition). MATERIAL AND METHODS: Correlation analyses in control-group
      comparisons. PARTICIPANTS: n=178 children; 91 children diagnosed with APD (51%)
      visiting 2nd-4th grade of a primary school; 87 second- to fourth-graders with
      typical development 49%). RESULTS: Different patterns were found not only between
      pSTM-tests and verbal-acoustic test tasks, but above all between children with
      and without APD. Neither pSTM for digits, nor for sentences or non-word
      repetition showed significant associations with a verbal-acoustic task for
      children without APD. In contrast, this was the case in children with APD in some
      pSTM measures with phoneme identification, phoneme analysis and dichotic word
      recognition (r=0.29-0.41; p<0.005, Bonferroni-adjusted). Obviously, pSTM is-
      besides variance according to the specific test tasks--a functional component
      which condensed in the verbal-acoustic test performance only in children with
      APD. CONCLUSIONS: This means that in primary school age, the role of pSTM and
      verbal-acoustic tasks is influenced by auditory processes in children with APD.

PMID- 26287639
TI  - Will It Be Beneficial To Simulate the Antifreeze Proteins at Ice Freezing
      Condition or at Lower Temperature?
AB  - Antifreeze proteins (AFPs) enable the polar living species to survive subzero
      temperature conditions through effective lowering of the freezing point of body
      fluids. At the molecular level, AFPs directly interact with the growing seeds of
      ice crystals to inhibit their formation. To understand the structural and dynamic
      aspects of this interaction at the atomistic level, molecular dynamics (MD)
      simulations were carried out on several type I AFPs at multiple temperatures,
      including the physiologically relevant temperature of 273 K, a lower temperature
      of 227 K, and the conventional 300 K. A comparison of the principal component
      analysis (PCA) and mean squared deviation plots for Winter flounder AFP, HPLC6
      (mutant of winter flounder AFP), Sculpin, and peptide 1m AFPs reveals that
      simulations at 273 and 227 K result in the formation of more conserved metastable
      states than at 300 K. Other parameters such as root-mean-square deviation (rmsd),
      solvent accessibility surface area (SASA), H-bonding and residual density
      function (RDF) also suggest the same. MD simulations with ice crystal, where AFPs
      are complexed to ice plane with TIP4P/ice water model, help in finding relevance
      of dynamic behavior, and physiological temperature becomes more pronounced.
      Additionally, a control study on a nonantifreeze protein (LL37) is included,
      which aids in exploring significant information. On the basis of this approach,
      it was found that AFPs at 273 and 227 K display relevant dynamic properties that
      appear at 300 K for nonantifreeze proteins. The present study hence emphasizes
      the importance of performing computational simulations for antifreeze proteins at
      the physiologically relevant temperature (273 K), and even at lower temperatures
      (like 227 K), rather than at room temperatures (300 K). 

PMID- 26287640
TI  - Traumatic Pediatric Posterior Fossa Extradural Hematomas: A Tertiary-Care Trauma
      Center Experience from India.
AB  - INTRODUCTION: Traumatic posterior fossa extradural hematomas (PFEDH) are rare
      lesions constituting <10% of all extradural hematomas. Reliance on clinical
      findings alone is not recommended as these are nonspecific; for all suspicious
      cases, it is advisable to conduct a CT scan. Only a handful of pediatric studies
      have been reported analyzing the outcome of such lesions. The aim of our study
      was to analyze outcomes for children with PFEDH managed at our apex trauma
      center. MATERIALS AND METHODS: We conducted a retrospective analysis of pediatric
      patients (<=18 years) admitted with a diagnosis of traumatic PFEDH from January
      2008 to February 2014. RESULTS: Of 22 patients, 16 were managed surgically (group
      1) and 6 conservatively (group 2); 1 failed conservative treatment (due to an
      increased EDH volume). Mean age was 11.7 years (range 2-18 years). Falls were the
      most common cause of injury. Vomiting and loss of consciousness were the most
      frequent presenting features. There were 18 mild, 2 moderate and 2 severe head
      injuries. The mean volume of EDH was 37.1 ml (range 18-100 ml) and 10.3 ml (8-16
      ml) in the operative and conservative subgroups, respectively. Occipital bone
      fracture was seen in 16 cases with supratentorial extension in 11. Four
      complications were noted in 3 cases. Mean follow-up duration was 25.1 months
      (range 3-34 months). Except for 1 patient, all had excellent outcomes. There was
      no mortality. CONCLUSIONS: Traumatic pediatric PFEDHs are rare. Both the clinical
      status of the patient and the volume of the hematoma need to be assessed before
      deciding on surgery. Most cases have associated occipital bone fractures and
      around half have supratentorial extension; these need to be carefully assessed
      preoperatively. Torrential venous bleeding can be a major problem due to rupture
      of the adjacent sinuses. Timely intervention is crucial for achieving good
      outcome, keeping in view a low threshold for surgical evacuation. Although not
      innovative, this second-largest case series provides additional data and
      contributes to the existing literature on such lesions in pediatric patients.

PMID- 26287641
TI  - A high-spin organic diradical as a spin filter.
AB  - Here, in this work we have designed a molecular bridge structure which can be
      used as a spin filter where the prototypical highly ferromagnetic m-phenylene
      connected bis(aminoxyl) diradical is used as a bridging fragment between two semi
      infinitely widened gold (Au) electrodes along the [100] direction. A state-of-the
      art non-equilibrium Green function's (NEGF) method coupled with the density
      functional theory (DFT) was carried out on this two-probe molecular bridge system
      to understand its electrical spin transport characteristics. The spin current at
      various bias voltages from 0.00 V to 4.00 V at intervals of 0.20 V for this Au
      diradical-Au molecular junction is evaluated. We also quantify the bias-dependent
      spin injection coefficients (BDSIC) at different bias voltages and also the spin
      filter efficiency at equilibrium, i.e., at zero bias voltage. Also plots of BDSIC
      vs. voltage, the up- and down-spin current vs. voltage (I-V) curves, and density
      of states (DOS) at zero bias voltage are evaluated. 

PMID- 26287643
TI  - The relationship between transmurality of ischemic scars and the heart rate of
      ventricular tachycardia.
AB  - AIMS: The relationship between the heart rate of ventricular tachycardia (VT) and
      the transmurality of ischemic scars was assessed by a new semiautomatic
      coordinate-based analysis of late gadolinium-enhanced cardiac magnetic resonance
      (LGE-CMR) images. METHODS AND RESULTS: Twenty patients assessed by LGE-CMR before
      implantation of implantable cardioverter defibrillator (ICD) with verified VT
      during the first year following ICD implantation were included. Scar was defined
      by pixels with a signal intensity >= 50% of maximum signal intensity. All pixels
      were assigned a coordinate position between endo- and epicardium (lambda) and the
      angle of the heart axis (phi). Based upon the lambda and phi values, multiple
      scar features were computed for all scarred areas. These features were correlated
      to VT heart rate across the complete range of transmurality. The strongest
      correlation with univariate regression was found between VT heart rate and the
      sum of transmurality when the maximum transmurality of these features was >= 90%
      (R-square = 0.47). In multiple regressions analysis, the strongest relationship
      with VT heart rate was found with a maximum transmurality >= 90% and by a
      combination of scar size, transmurality, and endocardial extent of infarction (R
      square = 0.64). CONCLUSION: Transmurality is the strongest predictor of VT heart
      rate both in univariate and multivariate models. The strongest relationships were
      found at a transmurality level > 90%.

PMID- 26287644
TI  - The association of the platelet-to-lymphocyte ratio with mitral annular
      calcification.
AB  - OBJECTIVES: Mitral annular calcification (MAC) and atherosclerosis are similar in
      regard to risk factors and pathogenesis. Increased platelet-to-lymphocyte ratio
      (PLR) has been shown to be associated with atherosclerotic diseases in previous
      studies. In this study, we aimed to show the association of PLR levels with the
      presence of MAC. DESIGN: A total of 1060 patients [n = 704 MAC (+), and n = 356
      MAC (-)] who were admitted to our cardiology department were enrolled between
      January 2014 and December 2014. Demographic, clinical, and laboratory parameters
      of all participants were recorded. PLR was calculated from the complete blood
      count. RESULTS: The MAC (+) group comprised of those older in age and having a
      higher rate of hypertension. The mean PLR value was also significantly higher in
      the MAC (+) group, as compared to that in the MAC (-) group (129.1 +/- 32.2 vs
      103.5 +/- 23.8, p < 0.001). There was a statistically significant and positive
      correlation between the neutrophil-to-lymphocyte ratio (NLR) and PLR (r = 0.644,
      p < 0.001). Age, hypertension, mean platelet volume, NLR, and PLR (OR: 1.109, 95%
      CI: 1.101-1.123, p < 0.001) were independently associated with the presence of
      MAC. CONCLUSIONS: Our results demonstrated that the PLR was significantly
      increased in patients with MAC, and that the PLR was independently associated
      with the presence of MAC.

PMID- 26287645
TI  - Soluble ST2 and myocardial fibrosis in 3T cardiac magnetic resonance.
AB  - OBJECTIVE: The soluble form of ST2 (sST2) is a novel laboratory parameter for
      cardiac risk prediction, and over the past years, several studies have tried to
      evaluate its utility, especially in the management of heart failure. We
      investigated whether increased serum levels of sST2 show a characteristic
      pathomorphologic pattern in 3-Tesla cardiac magnetic resonance imaging (CMRI).
      METHODS: One hundred and fifty-six patients referred to 3T CMRI due to suspected
      coronary artery disease (CAD) or myocarditis were prospectively enrolled in the
      study. Ninety patients were diagnosed with CAD, 22 patients with myocarditis, and
      44 patients, who constituted the reference group, showed no pathologic CMRI
      pattern. RESULTS: There was no significant difference between the sST2 values for
      patients in the reference group and patients with CAD or myocarditis. The sST2
      concentration showed a weak correlation with the NYHA functional class (P =
      0.002, r = 0.22), but correlation of sST2 and LGE, left ventricular parameters,
      and LVEF could not be seen. In contrast NT-proBNP was positively correlated to
      left ventricular parameters, LGE, and NYHA class function (P < 0.05).
      Additionally, it showed an inverse relationship to LVEF (P < 0.001, r = - 0.42).
      CONCLUSIONS: Soluble ST2 is not able to detect myocardial scar and should not be
      used alone as a parameter for detection of inflammation and myocardial scar
      formation.

PMID- 26287646
TI  - Nursing Needs Big Data and Big Data Needs Nursing.
AB  - PURPOSE: Contemporary big data initiatives in health care will benefit from
      greater integration with nursing science and nursing practice; in turn, nursing
      science and nursing practice has much to gain from the data science initiatives.
      Big data arises secondary to scholarly inquiry (e.g., -omics) and everyday
      observations like cardiac flow sensors or Twitter feeds. Data science methods
      that are emerging ensure that these data be leveraged to improve patient care.
      ORGANIZING CONSTRUCT: Big data encompasses data that exceed human comprehension,
      that exist at a volume unmanageable by standard computer systems, that arrive at
      a velocity not under the control of the investigator and possess a level of
      imprecision not found in traditional inquiry. Data science methods are emerging
      to manage and gain insights from big data. METHODS: The primary methods included
      investigation of emerging federal big data initiatives, and exploration of
      exemplars from nursing informatics research to benchmark where nursing is already
      poised to participate in the big data revolution. We provide observations and
      reflections on experiences in the emerging big data initiatives. CONCLUSIONS:
      Existing approaches to large data set analysis provide a necessary but not
      sufficient foundation for nursing to participate in the big data revolution.
      Nursing's Social Policy Statement guides a principled, ethical perspective on big
      data and data science. There are implications for basic and advanced practice
      clinical nurses in practice, for the nurse scientist who collaborates with data
      scientists, and for the nurse data scientist. CLINICAL RELEVANCE: Big data and
      data science has the potential to provide greater richness in understanding
      patient phenomena and in tailoring interventional strategies that are
      personalized to the patient.

PMID- 26287648
TI  - Insular cortex activity and the evocation of laughter.
AB  - The insular cortex is fundamentally involved in the processing of interoceptive
      information. It has been postulated that the integrative monitoring of the bodily
      responses to environmental stimuli is crucial for the recognition and experience
      of emotions. Because emotional arousal is known to be closely coupled to
      functions of the anterior insula, we suspected laughter to be associated
      primarily with neuronal activity in this region. An anatomically constrained re
      analysis of our imaging data pertaining to ticklish laughter, to inhibited
      ticklish laughter, and to voluntary laughter revealed regional differences in the
      levels of neuronal activity in the posterior and mid-/anterior portions of the
      insula. Ticklish laughter was associated specifically with right ventral anterior
      insular activity, which was not detected under the other two conditions. Hence,
      apparently, only laughter that is evoked as an emotional response bears the
      signature of autonomic arousal in the insular cortex.

PMID- 26287647
TI  - Longitudinal smoking patterns in survivors of childhood cancer: An update from
      the Childhood Cancer Survivor Study.
AB  - BACKGROUND: Survivors of pediatric cancer have elevated risks of mortality and
      morbidity. Many late adverse effects associated with cancer treatment (eg, second
      cancers and cardiac and pulmonary disease) are also associated with cigarette
      smoking, and this suggests that survivors who smoke may be at high risk for these
      conditions. METHODS: This study examined the self-reported smoking status for
      9397 adult survivors of childhood cancer across 3 questionnaires (median time
      interval, 13 years). The smoking prevalence among survivors was compared with the
      smoking prevalence among siblings and the prevalence expected on the basis of age
      , sex-, race-, and calendar time-specific rates in the US population.
      Multivariable regression models examined characteristics associated with
      longitudinal smoking patterns across all 3 questionnaires. RESULTS: At the
      baseline, 19% of survivors were current smokers, whereas 24% of siblings were
      current smokers, and 29% were expected to be current smokers on the basis of US
      rates. Current smoking among survivors dropped to 16% and 14% on follow-up
      questionnaires, with similar decreases in the sibling prevalence and the expected
      prevalence. Characteristics associated with consistent never-smoking included a
      higher household income (relative risk [RR], 1.16; 95% confidence interval [CI],
      1.08-1.25), higher education (RR, 1.32; 95% CI, 1.22-1.43), and receipt of
      cranial radiation therapy (RR, 1.08; 95% CI, 1.03-1.14). Psychological distress
      (RR, 0.86; 95% CI, 0.80-0.92) and heavy alcohol drinking (RR, 0.64; 95% CI, 0.58
      0.71) were inversely associated. Among ever-smokers, a higher income (RR, 1.17;
      95% CI, 1.04-1.32) and education (RR, 1.23; 95% CI, 1.10-1.38) were associated
      with quitting, whereas cranial radiation (RR, 0.86; 95% CI, 0.76-0.97) and
      psychological distress (RR, 0.80; 95% CI, 0.72-0.90) were associated with not
      having quit. The development of adverse health conditions was not associated with
      smoking patterns. CONCLUSIONS: Despite modest declines in smoking prevalence, the
      substantial number of consistent current smokers reinforces the need for
      continued development of effective smoking interventions for survivors.

PMID- 26287649
TI  - Antibiotics in cell culture: friend or foe? Suppression of keratinocyte growth
      and differentiation in monolayer cultures and 3D skin models.

PMID- 26287651
TI  - Adsorption of Hydrophobin-Protein Mixtures at the Air-Water Interface: The Impact
      of pH and Electrolyte.
AB  - The adsorption of the proteins beta-casein, beta-lactoglobulin, and hydrophobin,
      and the protein mixtures of beta-casein/hydrophobin and beta
      lactoglobulin/hydrophobin have been studied at the air-water interface by neutron
      reflectivity, NR. Changing the solution pH from 7 to 2.6 has relatively little
      impact on the adsorption of hydrophobin or beta-lactoglobulin, but results in a
      substantial change in the structure of the adsorbed layer of beta-casein. In beta
      lactoglobulin/hydrophobin mixtures, the adsorption is dominated by the
      hydrophobin adsorption, and is independent of the hydrophobin or beta
      lactoglobulin concentration and solution pH. At pH 2.6, the adsorption of the
      beta-casein/hydrophobin mixtures is dominated by the hydrophobin adsorption over
      the range of beta-casein concentrations studied. At pH 4 and 7, the adsorption of
      beta-casein/hydrophobin mixtures is dominated by the hydrophobin adsorption at
      low beta-casein concentrations. At higher beta-casein concentrations, beta-casein
      is adsorbed onto the surface monolayer of hydrophobin, and some interpenetration
      between the two proteins occurs. These results illustrate the importance of pH on
      the intermolecular interactions between the two proteins at the interface. This
      is further confirmed by the impact of PBS, phosphate buffered saline, buffer and
      CaCl2 on the coadsorption and surface structure. The results provide an important
      insight into the adsorption properties of protein mixtures and their application
      in foam and emulsion stabilization. 

PMID- 26287650
TI  - High-Resolution Mapping of Biomass Burning Emissions in Three Tropical Regions.
AB  - Biomass burning in tropical regions plays a significant role in atmospheric
      pollution and climate change. This study quantified a comprehensive monthly
      biomass burning emissions inventory with 1 km high spatial resolution, which
      included the burning of vegetation, human waste, and fuelwood for 2010 in three
      tropical regions. The estimations were based on the available burned area product
      MCD64A1 and statistical data. The total emissions of all gases and aerosols were
      17382 Tg of CO2, 719 Tg of CO, 30 Tg of CH4, 29 Tg of NOx, 114 Tg of NMOC
      (nonmethane organic compounds), 7 Tg of SO2, 10 Tg of NH3, 79 Tg of PM2.5
      (particulate matter), 45 Tg of OC (organic carbon), and 6 Tg of BC (black
      carbon). Taking CO as an example, vegetation burning accounted for 74% (530 Tg)
      of the total CO emissions, followed by fuelwood combustion and human waste
      burning. Africa was the biggest emitter (440 Tg), larger than Central and South
      America (113 Tg) and South and Southeast Asia (166 Tg). We also noticed that the
      dominant fire types in vegetation burning of these three regions were woody
      savanna/shrubland, savanna/grassland, and forest, respectively. Although there
      were some slight overestimations, our results are supported by comparisons with
      previously published data.

PMID- 26287652
TI  - Family preferences for home or hospital care at diagnosis for children with
      diabetes in the DECIDE study.
AB  - AIMS: A diagnosis of Type 1 diabetes in childhood can be a difficult life event
      for children and families. For children who are not severely ill, initial home
      rather than hospital-based care at diagnosis is an option although there is
      little research on which is preferable. Practice varies widely, with long
      hospital stays in some countries and predominantly home-based care in others.
      This article reports on the comparative acceptability and experience of children
      with Type 1 diabetes and their parents taking part in the DECIDE study evaluating
      outcomes of home or hospital-based treatment from diagnosis in the UK. METHODS:
      Semi-structured interviews with 11 (pairs of) parents and seven children were
      conducted between 15 and 20 months post diagnosis. Interviewees were asked about
      adaptation to, management and impact of the diabetes diagnosis, and their
      experience of initial post-diagnosis treatment. RESULTS: There were no
      differences between trial arms in adaptation to, management of or impact of
      diabetes. Most interviewees wanted to be randomized to the 'home' arm initially
      but expressed a retrospective preference for whichever trial arm they had been
      in, and cited benefits relating to learning about diabetes management.
      CONCLUSIONS: The setting for early treatment did not appear to have a
      differential impact on families in the long term. However, the data presented
      here describe different experiences of early treatment settings from the
      perspective of children and their families, and factors that influenced how
      families felt initially about treatment setting. Further research could
      investigate the short-term benefits of both settings.

PMID- 26287653
TI  - microRNA160 dictates stage-specific auxin and cytokinin sensitivities and directs
      soybean nodule development.
AB  - Legume nodules result from coordinated interactions between the plant and
      nitrogen-fixing rhizobia. The phytohormone cytokinin promotes nodule formation,
      and recent findings suggest that the phytohormone auxin inhibits nodule
      formation. Here we show that microRNA160 (miR160) is a key signaling element that
      determines the auxin/cytokinin balance during nodule development in soybean
      (Glycine max). miR160 appears to promote auxin activity by suppressing the levels
      of the ARF10/16/17 family of repressor ARF transcription factors. Using
      quantitative PCR assays and a fluorescence miRNA sensor, we show that miR160
      levels are relatively low early during nodule formation and high in mature
      nodules. We had previously shown that ectopic expression of miR160 in soybean
      roots led to a severe reduction in nodule formation, coupled with enhanced
      sensitivity to auxin and reduced sensitivity to cytokinin. Here we show that
      exogenous cytokinin restores nodule formation in miR160 over-expressing roots.
      Therefore, low miR160 levels early during nodule development favor cytokinin
      activity required for nodule formation. Suppression of miR160 levels using a
      short tandem target mimic (STTM160) resulted in reduced sensitivity to auxin and
      enhanced sensitivity to cytokinin. In contrast to miR160 over-expressing roots,
      STTM160 roots had increased nodule formation, but nodule maturation was
      significantly delayed. Exogenous auxin partially restored proper nodule formation
      and maturation in STTM160 roots, suggesting that high miR160 activity later
      during nodule development favors auxin activity and promotes nodule maturation.
      Therefore, miR160 dictates developmental stage-specific sensitivities to auxin
      and cytokinin to direct proper nodule formation and maturation in soybean. 

PMID- 26287654
TI  - Preparation of Chemically-Tailored Copolymer Membranes with Tunable Ion Transport
      Properties.
AB  - Membranes derived from copolymer materials are a promising platform due to their
      straightforward fabrication and small yet tunable pore structures. However, most
      current applications of these membranes are limited to the size-selective
      filtration of solutes. In this study, to advance the utility of copolymer
      membranes beyond size-selective filtrations, a poly(acrylonitrile-r
      oligo(ethylene glycol) methyl ether methacrylate-r-glycidyl methacrylate) (P(AN-r
      OEGMA-r-GMA)) copolymer is used to fabricate membranes that can be chemically
      modified via straightforward schemes. The P(AN-r-OEGMA-r-GMA) copolymer is cast
      into asymmetric membranes using a nonsolvent induced phase separation technique.
      Then, the surface charge of the membrane is modified to tailor its performance
      for nanofiltration applications. The oxirane groups of the glycidyl methacrylate
      (GMA) moiety that line the pore walls of the membrane allows for both positively
      charged and negatively charged moieties to be introduced directly without any
      prior activation. Notably, the highly size-selective nanostructure of the
      copolymer materials is retained throughout the functionalization processes.
      Specifically, amine moieties are attached to the pore walls using the aminolysis
      of the oxirane groups. The resulting amine-functionalized membrane is positively
      charged and rejects up to 87% of the salt dissolved in a 10 mM magnesium chloride
      feed solution. Further modification of the amine-functionalized membrane with 4
      sulfophenyl isothiocyanate results in pore walls lined by sulfonic acid moieties.
      These negatively charged membranes reject up to 90% of a 10 mM sodium sulfate
      feed solution. Throughout the modification scheme, the membrane permeability
      remains equal to 1.5 L m(-2) h(-1) bar(-1) and the rejection of neutral solutes
      (i.e., sucrose and poly(ethylene oxide)) is consistent with the membrane having a
      single well-defined pore diameter of ~5 nm. The performance of the membrane as a
      function of ion valence number, solution pH, and ionic strength is investigated. 

PMID- 26287656
TI  - Identification of Synaptic Patterns of NMDA Receptor Subtypes Upon Direction
      Selective Rabbit Retinal Ganglion Cells.
AB  - PURPOSE: The objective of this study was to identify anisotropies that contribute
      to the directional preference of direction-selective retinal ganglion cells (DS
      RGCs) in the rabbit retina. We investigated the distributions of N-methyl-d
      aspartate receptor 1 (NMDAR1), NMDAR2A and NMDAR2B receptor subunits in the
      dendritic arbors of rabbit DS RGCs. METHODS: The distributions of the NMDAR
      subunits on the DS RGCs were determined using immunocytochemistry. DS RGCs were
      injected with Lucifer yellow, and the cells were identified by their
      characteristic morphology. The triple-labeled images of dendrites, kinesin II and
      NMDARs were visualized using confocal microscopy and were reconstructed from high
      resolution confocal images. RESULTS: We found no evidence of asymmetry in any of
      the NMDAR subunits examined on the dendritic arbors of both the ON and OFF layers
      of DS RGCs. CONCLUSIONS: Our results indicate that direction selectivity appears
      to lie in the neuronal circuitry afferent to the DS RGCs.

PMID- 26287655
TI  - Zellweger spectrum disorders: clinical manifestations in patients surviving into
      adulthood.
AB  - INTRODUCTION: We describe the natural history of patients with a Zellweger
      spectrum disorder (ZSD) surviving into adulthood. METHODS: Retrospective cohort
      study in patients with a genetically confirmed ZSD. RESULTS: All patients (n =
      19; aged 16-35 years) had a follow-up period of 1-24.4 years (mean 16 years).
      Seven patients had a progressive disease course, while 12 remained clinically
      stable during follow-up. Disease progression usually manifests in adolescence as
      a gait disorder, caused by central and/or peripheral nervous system involvement.
      Nine were capable of living a partly independent life with supported employment.
      Systematic MRI review revealed T2 hyperintense white matter abnormalities in the
      hilus of the dentate nucleus and/or peridentate region in nine out of 16
      patients. Biochemical analyses in blood showed abnormal peroxisomal biomarkers in
      all patients in infancy and childhood, whereas in adolescence/adulthood we
      observed normalization of some metabolites. CONCLUSIONS: The patients described
      here represent a distinct subgroup within the ZSDs who survive into adulthood.
      Most remain stable over many years. Disease progression may occur and is mainly
      due to cerebral and cerebellar white matter abnormalities, and peripheral
      neuropathy.

PMID- 26287657
TI  - Structure and Validity of Affect Knowledge Test (AKT) in a Sample of Italian
      Preschoolers.
AB  - The authors' main goals were to examine whether the Affect Knowledge Test's (AKT)
      factor structure would be represented by a two-factor model (i.e., emotion
      recognition and situation knowledge) or by a one-factor model in Italian
      preschoolers (N = 164; M = 4.24 years, SD = 1.09 years). The concurrent validity
      of the AKT was further examined using measures of social competence. The findings
      replicated a model of emotion knowledge, with emotion recognition and situation
      knowledge as distinct but interrelated factors. Gender and age differences showed
      that older children and girls displayed higher scores in situation knowledge than
      younger children and boys. Additionally, our validity model of the AKT
      demonstrated that emotion recognition preceded situation knowledge, which in turn
      was positively related to children's sensitive or cooperative behaviors and
      negatively associated with anxious or withdrawn behaviors. Our results suggest
      that the use of the AKT may help the teachers to evaluate children's level on
      emotional knowledge that in turn might impact on children's positive social
      relationships within classroom in Italy. 

PMID- 26287658
TI  - Biocatalytic synthesis of 3,4,5,3',5'-pentahydroxy-trans-stilbene from
      piceatannol by two-component flavin-dependent monooxygenase HpaBC.
AB  - HpaBC monooxygenase was previously reported to hydroxylate resveratrol to
      piceatannol. In this article, we report a novel catalytic activity of HpaBC for
      the synthesis of a pentahydroxylated stilbene. When Escherichia coli cells
      expressing HpaBC were incubated with resveratrol, the resulting piceatannol was
      further converted to a new product. This product was identified by mass
      spectrometry and NMR spectroscopy as a 5-hydroxylated piceatannol, 3,4,5,3',5'
      pentahydroxy-trans-stilbene (PHS), which is a reportedly valuable biologically
      active stilbene derivative. We attempted to produce PHS from piceatannol on a
      flask scale. After examining the effects of detergents and buffers on PHS
      production, E. coli cells expressing HpaBC efficiently hydroxylated piceatannol
      to PHS in a reaction mixture containing 1.5% (v/v) Tween 80 and 100 mM 3
      morpholinopropanesulfonic acid-NaOH buffer at pH 7.5. Under the optimized
      conditions, the whole cells regioselectively hydroxylated piceatannol, and the
      production of PHS reached 6.9 mM (1.8 g L(-1)) in 48 h.

PMID- 26287659
TI  - Short term exendin-4 treatment reduces markers of metabolic disorders in female
      offspring of obese rat dams.
AB  - OBJECTIVES: Maternal obesity imposes significant health risks in the offspring
      including diabetes and dyslipidemia. We previously showed that the hypoglycaemic
      agent exendin-4 (Ex-4) administered from weaning can reverse the maternal impact
      of 'transmitted disorders' in such offspring. However daily injection for six
      weeks was required and the beneficial effect may lapse upon drug withdrawal. This
      study aimed to investigate whether short term Ex-4 treatment during suckling
      period in a rodent model can reverse transmitted metabolic disorders due to
      maternal obesity. METHODS: Maternal obesity was induced in female Sprague Dawley
      rats by high-fat diet feeding for 6 weeks, throughout gestation and lactation.
      Female offspring were treated with Ex-4 (5MUg/kg/day) between postnatal day (P) 4
      and 14. Female offspring were harvested at weaning (P20). Lipid and glucose
      metabolic markers were measured in the liver and fat. Appetite regulators were
      measured in the plasma and hypothalamus. RESULTS: Maternal obesity significantly
      increased body weight, fat mass, and liver weight in the offspring. There was an
      associated inhibition of peroxisomal proliferator activated receptor gamma
      coactivator 1alpha (PGC1alpha), increased fatty acid synthase (FASN) expression
      in the liver, and reduced adipocyte triglyceride lipase (ATGL) expression. It
      also increased the plasma gut hormone ghrelin and reduced glucagon-like peptide
      1. Ex-4 treatment partially reversed the maternal impact on adiposity and
      impaired lipid metabolism in the offspring, with increased liver PGC1alpha and
      inhibition of FASN mRNA expression. Ex-4 treatment also increased the expression
      of a novel fat depletion gene a2-zinc-glycoprotein 1 in the fat tissue.
      CONCLUSION: Short term Ex-4 treatment during the suckling period significantly
      improved the metabolic profile in the offspring from the obese mothers at
      weaning. Long-term studies are needed to follow such offspring to adulthood to
      examine the sustained effects of Ex-4 in preventing the development of metabolic
      disease.

PMID- 26287660
TI  - Variant Rett syndrome in a girl with a pericentric X-chromosome inversion leading
      to epigenetic changes and overexpression of the MECP2 gene.
AB  - Rett syndrome is a neurodevelopmental disorder caused by mutations in the MECP2
      gene. We investigated the genetic basis of disease in a female patient with a
      Rett-like clinical. Karyotype analysis revealed a pericentric inversion in the X
      chromosome -46,X,inv(X)(p22.1q28), with breakpoints in the cytobands where the
      MECP2 and CDKL5 genes are located. FISH analysis revealed that the MECP2 gene is
      not dislocated by the inversion. However, and in spite of a balanced pattern of X
      inactivation, this patient displayed hypomethylation and an overexpression of the
      MECP2 gene at the mRNA level in the lymphocytes (mean fold change: 2.55+/-0.38)
      in comparison to a group of control individuals; the expression of the CDKL5 gene
      was similar to that of controls (mean fold change: 0.98+/-0.10). No gains or
      losses were detected in the breakpoint regions encompassing known or suspected
      transcription regulatory elements. We propose that the de-regulation of MECP2
      expression in this patient may be due to alterations in long-range genomic
      interactions caused by the inversion and hypothesize that this type of epigenetic
      de-regulation of the MECP2 may be present in other RTT-like patients. 

PMID- 26287661
TI  - Combination of 13 cis-retinoic acid and tolfenamic acid induces apoptosis and
      effectively inhibits high-risk neuroblastoma cell proliferation.
AB  - Chemotherapeutic regimens used for the treatment of Neuroblastoma (NB) cause long
      term side effects in pediatric patients. NB arises in immature sympathetic nerve
      cells and primarily affects infants and children. A high rate of relapse in high
      risk neuroblastoma (HRNB) necessitates the development of alternative strategies
      for effective treatment. This study investigated the efficacy of a small
      molecule, tolfenamic acid (TA), for enhancing the anti-proliferative effect of 13
      cis-retinoic acid (RA) in HRNB cell lines. LA1-55n and SH-SY5Y cells were treated
      with TA (30MUM) or RA (20MUM) or both (optimized doses, derived from dose curves)
      for 48h and tested the effect on cell viability, apoptosis and selected molecular
      markers (Sp1, survivin, AKT and ERK1/2). Cell viability and caspase activity were
      measured using the CellTiter-Glo and Caspase-Glo kits. The apoptotic cell
      population was determined by flow cytometry with Annexin-V staining. The
      expression of Sp1, survivin, AKT, ERK1/2 and c-PARP was evaluated by Western
      blots. The combination therapy of TA and RA resulted in significant inhibition of
      cell viability (p<0.0001) when compared to individual agents. The anti
      proliferative effect is accompanied by a decrease in Sp1 and survivin expression
      and an increase in apoptotic markers, Annexin-V positive cells, caspase 3/7
      activity and c-PARP levels. Notably, TA+RA combination also caused down
      regulation of AKT and ERK1/2 suggesting a distinct impact on survival and
      proliferation pathways via signaling cascades. This study demonstrates that the
      TA mediated inhibition of Sp1 in combination with RA provides a novel therapeutic
      strategy for the effective treatment of HRNB in children. 

PMID- 26287663
TI  - Structure- and temperature-sensitive photoluminescence in a novel phosphate red
      phosphor RbZnPO4:Eu(3.).
AB  - A novel phosphate RbZnPO4 has been developed for the first time and the
      characteristic crystal structure of RbZnPO4 has been investigated in detail,
      based on the Fourier transform infrared reflection spectra and the structure
      refinement of X-ray diffraction data. After doping with Eu(3+),RbZnPO4:Eu(3+)
      shows distinctive deep red emission with dominating peaks at 596 and 701 nm. To
      provide a reasonable explanation for the relationship between photoluminescence
      and structure, the photoluminescence property has been discussed by analyzing the
      particular local ligand environment and site occupation of Eu(3+) in RbZnPO4.
      More interestingly, temperature-sensitive emission behavior was found in
      RbZnPO4:Eu(3+). Through the synthetical analysis of the configurational
      coordinate diagram, the charge compensation experiment and the CASTEP band
      structure calculation, a complex underlying mechanism is proposed to explain the
      abnormal temperature-sensitive emission behavior in RbZnPO4:Eu(3+). The mechanism
      could be helpful for better understanding the thermal quenching process of Eu(3+)
      in RbZnPO4 and also as a reference in some other temperature-sensitive phosphors.

PMID- 26287664
TI  - Correlation of TSLP, IL-33, and CD4 + CD25 + FOXP3 + T regulatory (Treg) in
      pediatric asthma.
AB  - OBJECTIVE: Newly discovered cytokines TSLP and IL33 are being studied as
      important indicators of Th2 inflammation and their effect on Treg cells is likely
      to modulate immune response. We attempted to study TSLP and IL-33 and then
      correlated with Tregs in order to find possible biomarker in these patients.
      METHODS: Sixty-five children (37 with asthma only and 28 with asthma and
      rhinitis) aged 6.4 +/- 3.2 years (patient group) and 15 healthy children aged 8.0
      +/- 2.6 years (control group) were recruited in this study. In vitro analysis of
      TSLP and IL-33 was done in serum samples of 65 newly diagnosed children for
      allergic asthma and 15 healthy children using the sandwich ELISA method. The
      expression of Treg cells (CD4 + CD25 + FOXP3+) was analyzed by flow cytometry.
      RESULTS: The mean TSLP in the patient group (592 +/- 68 pg/ml) was significantly
      higher than controls (215 +/- 45 pg/ml) (p < 0.05). Alternatively, the expression
      of FOXP3 + T reg cells was significantly lower in the patient group (52 +/- 36)
      compared with the controls (95.9 +/- 3.6) (p = 0.003). IL-33 was also
      significantly higher (4044 +/- 413 pg/ml) in the patient group compared with the
      controls (3282 +/- 331.5 pg/ml) (p = 0.0001). The expression of Treg cells was
      negatively correlated with the TSLP (r = -0.23, p = 0.07). Asthma control test
      (ACT) was also negatively correlated with TSLP in the patient group (r = -0.14, p
      > 0.05). CONCLUSION: Children with asthma show elevated serum levels of TSLP,
      which correlated negatively with asthma control test and Treg cells. TSLP may be
      used as a biomarker for inflammation in pediatric asthma patients.

PMID- 26287665
TI  - Communication: Improving the View From This Side.

PMID- 26287666
TI  - Biomechanical Analysis of a Dynamic Stability Test System to Evoke Sway and Step
      Recovery.
AB  - This paper reports on the dynamic analysis and experimental validation of a
      method to perturb the balance of subjects in quiet standing. Electronically
      released weights pull the subject's waist through a specified displacement sensed
      by a photoelectric sensor. A dynamic model is derived that computes the force
      applied to the subject as a function of waist acceleration. This model accurately
      predicts the acceleration of mock subjects (suspended masses) with high
      repeatability. The validity and simplicity of this model suggest that this method
      can provide a standard for provocation testing on stable surfaces. Proof-of
      concept trials on human subjects demonstrate that the device can be used with a
      force platform and motion tracking and that the device can induce both sway and
      step recoveries in healthy male adults. 

PMID- 26287668
TI  - Stretchable and transparent electrodes based on in-plane structures.
AB  - Stretchable electronics has attracted great interest with compelling potential
      applications that require reliable operation under mechanical deformation.
      Achieving stretchability in devices, however, requires a deeper understanding of
      nanoscale materials and mechanics beyond the success of flexible electronics. In
      this regard, tremendous research efforts have been dedicated toward developing
      stretchable electrodes, which are one of the most important building blocks for
      stretchable electronics. Stretchable transparent thin-film electrodes, which
      retain their electrical conductivity and optical transparency under mechanical
      deformation, are particularly important for the favourable application of
      stretchable devices. This minireview summarizes recent advances in stretchable
      transparent thin-film electrodes, especially employing strategies based on in
      plane structures. Various approaches using metal nanomaterials, carbon
      nanomaterials, and their hybrids are described in terms of preparation processes
      and their optoelectronic/mechanical properties. Some challenges and perspectives
      for further advances in stretchable transparent electrodes are also discussed. 

PMID- 26287667
TI  - TLR3 agonist and Sorafenib combinatorial therapy promotes immune activation and
      controls hepatocellular carcinoma progression.
AB  - Hepatocellular carcinoma (HCC) is associated with high mortality and the current
      therapy for advanced HCC, Sorafenib, offers limited survival benefits. Here we
      assessed whether combining the TLR3 agonist: lysine-stabilized polyinosinic
      polycytidylic-acid (poly-ICLC) with Sorafenib could enhance tumor control in HCC.
      Combinatorial therapy with poly-ICLC and Sorafenib increased apoptosis and
      reduced proliferation of HCC cell lines in vitro, in association with impaired
      phosphorylation of AKT, MEK and ERK. In vivo, the combinatorial treatment
      enhanced control of tumor growth in two mouse models: one transplanted with Hepa
      1-6 cells, and the other with liver tumors induced using the Sleeping beauty
      transposon. Tumor cell apoptosis and host immune responses in the tumor
      microenvironment were enhanced. Particularly, the activation of local NK cells, T
      cells, macrophages and dendritic cells was enhanced. Decreased expression of the
      inhibitory signaling molecules PD-1 and PD-L1 was observed in tumor-infiltrating
      CD8+ T cells and tumor cells, respectively. Tumor infiltration by monocytic
      myeloid derived suppressor cells (Mo-MDSC) was also reduced indicating the
      reversion of the immunosuppressive tumor microenvironment. Our data demonstrated
      that the combinatorial therapy with poly-ICLC and Sorafenib enhances tumor
      control and local immune response hence providing a rationale for future clinical
      studies. 

PMID- 26287669
TI  - Frequencies of HKalphaalpha and anti-HKalphaalpha Alleles in Chinese Carriers of
      Silent Deletional alpha-Thalassemia.
AB  - The HKalphaalpha (HongKongalphaalpha) allele is an unusual rearrangement of the
      alpha-globin gene cluster containing both the -alpha(3.7) (rightward) and
      alphaalphaalpha(anti 4.2) crossover deletion/duplication. The anti-HKalphaalpha
      (anti-HongKongalphaalpha) allele is the reciprocal product containing both the 
      alpha(4.2) (leftward) and alphaalphaalpha(anti 3.7) unequal crossover
      deletion/duplication. In clinical practice of thalassemia screening, gap
      polymerase chain reaction (gap-PCR) approaches are used to detect the common 
      alpha(3.7) and -alpha(4.2) deletions of alpha-thalassemia (alpha-thal). Because
      the HKalphaalpha and anti-HKalphaalpha alleles also contain the single alpha
      globin gene deletion, individuals with these alleles would be misdiagnosed as 
      alpha(3.7) or -alpha(4.2) carriers. This would likely produce misleading or
      incorrect information in genetic counseling. In this study, we investigated the
      HKalphaalpha and anti-HKalphaalpha alleles in Chinese carriers of silent
      deletional alpha-thal, and reported their frequencies to be 2.27 and 0.35% in 
      alpha(3.7) and -alpha(4.2) carriers, respectively. Given the rarity of the
      HKalphaalpha and anti-HKalphaalpha alleles, a routine screening for these two
      rearrangements are unlikely to be necessary on most occasions. 

PMID- 26287670
TI  - Sodium Intake and Socioeconomic Status as Risk Factors for Development of Age
      Related Cataracts: The Korea National Health and Nutrition Examination Survey.
AB  - PURPOSE: Cataract is a very prevalent ocular disorder, and environmental risk
      factors for age-related cataracts have been widely investigated. We aimed to
      evaluate an association of dietary sodium intake and socioeconomic factors with
      the development of age-related cataracts. METHODS: A cross-sectional case-control
      study based on the 2008-2011 Korea National Health and Nutrition Examination
      Survey. Dietary sodium intake was estimated using urinary sodium to creatinine
      ratio (U[Na+]/Cr). RESULTS: Among a total 12,693 participants, 2,687 (21.1%) had
      cataracts and 10,006 patients without cataracts served as controls. The
      prevalence of cataracts increased with age and quartiles of U[Na+]/Cr (p for
      trend < 0.001). Multivariate logistic regression analyses revealed that factors
      related to the development of cataracts were age >= 50 years (adjusted odds ratio
      [aOR] 15.34, 95% confidence interval [CI] 13.31-17.69), low income (aOR 1.85, 95%
      CI 1.64-2.09), low educational attainment (aOR 1.76, 95% CI 1.57-1.96), and high
      sodium intake (U[Na+]/Cr > 16.4 mmol/mmol; aOR 1.29, 95% CI 1.16-1.44). In a
      subgroup analysis, a robust effect on cataracts across U[Na+]/Cr quartiles was
      observed in patients >= 50 years of age (aOR 1.11, 95% CI 1.04-1.18), though not
      in younger patients (aOR 1.06, 95% CI 0.96-1.17). CONCLUSIONS: Our results
      suggest that high sodium intake and low socioeconomic status may affect the
      development of cataracts, and that a low-salt diet could be helpful for the
      prevention of cataracts in an older population. Furthermore, efforts to close
      gaps in health services due to socioeconomic factors may contribute to a
      reduction in the prevalence of cataracts.

PMID- 26287671
TI  - Estimating the Effects of Habitat and Biological Interactions in an Avian
      Community.
AB  - We used repeated sightings of individual birds encountered in community-level
      surveys to investigate the relative roles of habitat and biological interactions
      in determining the distribution and abundance of each species. To analyze these
      data, we developed a multispecies N-mixture model that allowed estimation of both
      positive and negative correlations between abundances of different species while
      also estimating the effects of habitat and the effects of errors in detection of
      each species. Using a combination of single- and multispecies N-mixture modeling,
      we examined for each species whether our measures of habitat were sufficient to
      account for the variation in encounter histories of individual birds or whether
      other habitat variables or interactions with other species needed to be
      considered. In the community that we studied, habitat appeared to be more
      influential than biological interactions in determining the distribution and
      abundance of most avian species. Our results lend support to the hypothesis that
      abundances of forest specialists are negatively affected by forest fragmentation.
      Our results also suggest that many species were associated with particular types
      of vegetation as measured by structural attributes of the forests. The abundances
      of 6 of the 73 species observed in our study were strongly correlated. These
      species included large birds (American Crow (Corvus brachyrhynchos) and Red
      winged Blackbird (Agelaius phoeniceus)) that forage on the ground in open
      habitats and small birds (Red-eyed Vireo (Vireo olivaceus), House Wren
      (Troglodytes aedon), Hooded Warbler (Setophaga citrina), and Prairie Warbler
      (Setophaga discolor)) that are associated with dense shrub cover. Species
      abundances were positively correlated within each size group and negatively
      correlated between groups. Except for the American Crow, which preys on eggs and
      nestlings of small song birds, none of the other 5 species is known to display
      direct interactions, so we suspect that the correlations may have been associated
      with species-specific responses to habitat components not adequately measured by
      our covariates. 

PMID- 26287672
TI  - Kinetic Study on Mutagenic Chemical Degradation through Three Pot Synthesiszed
      Graphene@ZnO Nanocomposite.
AB  - The study was taken up with the objective to synthesize graphene-zinc oxide nano
      particles (NPs) nanocomposite (Gr@ZnO-Nc) via In-situ synthesis method. The
      structural, optical, thermal, electrical and photocatalytic properties of the
      synthesized Gr@ZnO-Nc were studied. The characterization data confirmed that the
      ZnO NPs were successfully incorporated into the graphene sheets. Further, TGA/DTA
      results exhibited an enhanced thermal stability of the Gr@ZnO-Nc compared with
      the graphene. The Gr@ZnO-Nc, graphene sheets were uniformly wrapped by ZnO NPs,
      which can protect graphene and delay their oxidation in air. The synthesized
      Gr@ZnO-Nc was used for the efficient photodegradation of a carcinogenic methyl
      orange (MO) dye. The results exhibited promising photodegradation of the MO dye
      under UV light irradiation through the production of reactive oxygen species
      (ROS). The promising effect of Gr@ZnO-Nc on the photodegradation properties was
      conferred by the large surface area which increased adsorption capacity, and the
      strong electron transfer ability. Thus, it is encouraging to conclude that the
      synthesized Gr@ZnO-Nc has environmental significance with its utility in
      remediation in the hazardous MO dye. 

PMID- 26287673
TI  - Papio Cranium from the Hominin-Bearing Site of Malapa: Implications for the
      Evolution of Modern Baboon Cranial Morphology and South African Plio-Pleistocene
      Biochronology.
AB  - A new partial cranium (UW 88-886) of the Plio-Pleistocene baboon Papio
      angusticeps from Malapa is identified, described and discussed. UW 88-886
      represents the only non-hominin primate yet recovered from Malapa and is
      important both in the context of baboon evolution as well as South African
      hominin site biochronology. The new specimen may represent the first appearance
      of modern baboon anatomy and coincides almost perfectly with molecular divergence
      date estimates for the origin of the modern P. hamadryas radiation. The fact that
      the Malapa specimen is dated between ~2.026-2.36 million years ago (Ma) also has
      implications for the biochronology of other South African Plio-Pleistocene sites
      where P. angusticeps is found. 

PMID- 26287675
TI  - TETs Link Hydrogen Sulfide to Immune Tolerance.
AB  - Demethylation of the Foxp3 locus maintains gene expression and Treg cell
      stability. Yang et al. (2015) show that the gasotransmitter hydrogen sulfide co
      operates with growth factor TGF-beta and interleukin-2 to activate Tet-mediated
      DNA demethylation of Foxp3 to promote immune tolerance.

PMID- 26287676
TI  - POPsicle for Fever! Cooling Down the Inflammasome.
AB  - Inhibition of the inflammasome might be beneficial for numerous inflammatory
      pathologies. In this issue of Immunity, de Almeida et al. (2015) report that the
      PYRIN domain-only protein (POP1) efficiently inhibits inflammasome activation,
      identifying it as a pan-inflammasome inhibitor.

PMID- 26287674
TI  - Evaluation of Aminoglycoside and Non-Aminoglycoside Compounds for Stop-Codon
      Readthrough Therapy in Four Lysosomal Storage Diseases.
AB  - Nonsense mutations are quite prevalent in inherited diseases. Readthrough drugs
      could provide a therapeutic option for any disease caused by this type of
      mutation. Geneticin (G418) and gentamicin were among the first to be described.
      Novel compounds have been generated, but only a few have shown improved results.
      PTC124 is the only compound to have reached clinical trials. Here we first
      investigated the readthrough effects of gentamicin on fibroblasts from one
      patient with Sanfilippo B, one with Sanfilippo C, and one with Maroteaux-Lamy. We
      found that ARSB activity (Maroteaux-Lamy case) resulted in an increase of 2-3
      folds and that the amount of this enzyme within the lysosomes was also increased,
      after treatment. Since the other two cases (Sanfilippo B and Sanfilippo C) did
      not respond to gentamicin, the treatments were extended with the use of geneticin
      and five non-aminoglycoside (PTC124, RTC13, RTC14, BZ6 and BZ16) readthrough
      compounds (RTCs). No recovery was observed at the enzyme activity level. However,
      mRNA recovery was observed in both cases, nearly a two-fold increase for
      Sanfilippo B fibroblasts with G418 and around 1.5 fold increase for Sanfilippo C
      cells with RTC14 and PTC124. Afterwards, some of the products were assessed
      through in vitro analyses for seven mutations in genes responsible for those
      diseases and, also, for Niemann-Pick A/B. Using the coupled
      transcription/translation system (TNT), the best results were obtained for SMPD1
      mutations with G418, reaching a 35% recovery at 0.25 MUg/ml, for the p.W168X
      mutation. The use of COS cells transfected with mutant cDNAs gave positive
      results for most of the mutations with some of the drugs, although to a different
      extent. The higher enzyme activity recovery, of around two-fold increase, was
      found for gentamicin on the ARSB p.W146X mutation. Our results are promising and
      consistent with those of other groups. Further studies of novel compounds are
      necessary to find those with more consistent efficacy and fewer toxic effects. 

PMID- 26287677
TI  - Gut-Pancreatic Axis AMPlified in Islets of Langerhans.
AB  - Microbially derived metabolites in the intestine regulate host immunity and
      impact disease pathophysiology in various organs. Sun et al. (2015) suggest a
      direct effect of microbial metabolites on pancreatic endocrine cells in
      regulating type 1 diabetes pathophysiology.

PMID- 26287678
TI  - Memory NK Cells Take Out the (Mitochondrial) Garbage.
AB  - The molecular mechanisms important to generate innate natural killer cell
      "memory" are poorly understood. In this issue of Immunity, O'Sullivan et al.
      (2015) demonstrate that mitophagy plays a critical role in natural killer cell
      memory formation following viral infection.

PMID- 26287679
TI  - ILC Lineage Specification: To Be or Not 11b, That Is the Question.
AB  - The transcription factor Bcl11b is important for T cell development and
      maintaining their phenotype. In this issue of Immunity, Califano et al. (2015)
      show that Bcl11b has a role in specifying type II innate lymphoid cell (ILC2)
      identity and blocks their conversion to ILC3s.

PMID- 26287680
TI  - Sweet NETs, Bitter Wounds.
AB  - What causes slow wound healing rates in diabetes is poorly understood. Wong et
      al. (2015) report that an increase in the deployment of neutrophil extracellular
      traps associated with hyperglycemia slows down wound healing.

PMID- 26287681
TI  - Interleukin-21-Producing CD4(+) T Cells Promote Type 2 Immunity to House Dust
      Mites.
AB  - Asthma is a T helper 2 (Th2)-cell-mediated disease; however, recent findings
      implicate Th17 and innate lymphoid cells also in regulating airway inflammation.
      Herein, we have demonstrated profound interleukin-21 (IL-21) production after
      house dust mite (HDM)-driven asthma by using T cell receptor (TCR) transgenic
      mice reactive to Dermatophagoides pteronyssinus 1 and an IL-21GFP reporter mouse.
      IL-21-producing cells in the mediastinal lymph node (mLN) bore characteristics of
      T follicular helper (Tfh) cells, whereas IL-21(+) cells in the lung did not
      express CXCR5 (a chemokine receptor expressed by Tfh cells) and were distinct
      from effector Th2 or Th17 cells. Il21r(-/-) mice developed reduced type 2
      responses and the IL-21 receptor (IL-21R) enhanced Th2 cell function in a cell
      intrinsic manner. Finally, administration of recombinant IL-21 and IL-25
      synergistically promoted airway eosinophilia primarily via effects on CD4(+)
      lymphocytes. This highlights an important Th2-cell-amplifying function of IL-21
      producing CD4(+) T cells in allergic airway inflammation.

PMID- 26287683
TI  - Most Tissue-Resident Macrophages Except Microglia Are Derived from Fetal
      Hematopoietic Stem Cells.
AB  - Macrophages are one of the most diverse cell populations in terms of their
      anatomical location and functional specialization during both homeostasis and
      disease. Although it has been shown in different fate mapping models that some
      macrophages present in adult tissues are already established during fetal
      development, their exact origins are still under debate. In the current study, we
      developed a fate mapping strain, based on the Kit locus, which allowed us to
      readdress "the origins" question. Different types of macrophages from various
      adult tissues were traced to their fetal or adult sources by inducing labeling in
      precursors at several time points either during fetal development or in adult
      mice. We show that all adult macrophages, resident or infiltrating, are progenies
      of classical hematopoietic stem cells (HSC) with the exception of microglia and,
      partially epidermal Langerhans cells, which are yolk sac (YS)-derived.

PMID- 26287682
TI  - Microbiota-Dependent Activation of an Autoreactive T Cell Receptor Provokes
      Autoimmunity in an Immunologically Privileged Site.
AB  - Activated retina-specific T cells that have acquired the ability to break through
      the blood-retinal barrier are thought to be causally involved in autoimmune
      uveitis, a major cause of human blindness. It is unclear where these autoreactive
      T cells first become activated, given that their cognate antigens are sequestered
      within the immune-privileged eye. We demonstrate in a novel mouse model of
      spontaneous uveitis that activation of retina-specific T cells is dependent on
      gut commensal microbiota. Retina-specific T cell activation involved signaling
      through the autoreactive T cell receptor (TCR) in response to non-cognate antigen
      in the intestine and was independent of the endogenous retinal autoantigen. Our
      findings not only have implications for the etiology of human uveitis, but also
      raise the possibility that activation of autoreactive TCRs by commensal microbes
      might be a more common trigger of autoimmune diseases than is currently
      appreciated.

PMID- 26287685
TI  - SnapShot: Integrated Type 2 Immune Responses.

PMID- 26287684
TI  - Identification of a Human Natural Killer Cell Lineage-Restricted Progenitor in
      Fetal and Adult Tissues.
AB  - Natural killer (NK) cells are cytotoxic lymphocytes and play a vital role in
      controlling viral infections and cancer. In contrast to B and T lymphopoiesis
      where cellular and regulatory pathways have been extensively characterized, the
      cellular stages of early human NK cell commitment remain poorly understood. Here
      we demonstrate that a Lin(-)CD34(+)CD38(+)CD123(-)CD45RA(+)CD7(+)CD10(+)CD127(-)
      population represents a NK lineage-restricted progenitor (NKP) in fetal
      development, umbilical cord blood, and adult tissues. The newly identified NKP
      has robust NK cell potential both in vitro and in vivo, generates functionally
      cytotoxic NK cells, and lacks the ability to produce T cells, B cells, myeloid
      cells, and innate lymphoid-like cells (ILCs). Our findings identify an early step
      to human NK cell commitment and provide new insights into the human hematopoietic
      hierarchy. 

PMID- 26287686
TI  - Dog Bite Prevention: Effect of a Short Educational Intervention for Preschool
      Children.
AB  - This study aimed to investigate whether preschool children can learn how to
      interpret dogs' behaviours, with the purpose of helping avoid dog bites. Three-
      to five-year-old children (N = 70) were tested on their ability to answer
      questions about dogs' emotional states before and after participating in either
      an educational intervention about dog behaviour (intervention group) or an
      activity about wild animals (control group). Children who had received training
      about dog behaviour (intervention group) were significantly better at judging the
      dogs' emotional states after the intervention compared to before. The frequency
      with which they referred to relevant behaviours in justifying their judgements
      also increased significantly. In contrast, the control group's performance did
      not differ significantly between the two testing times. These results indicate
      that preschool children can be taught how to correctly interpret dogs'
      behaviours. This implies that incorporating such training into prevention
      programmes may contribute to reducing dog bite incidents. 

PMID- 26287687
TI  - Identification of Salt Stress Biomarkers in Romanian Carpathian Populations of
      Picea abies (L.) Karst.
AB  - The Norway spruce (Picea abies), the most important tree species in European
      forests, is relatively sensitive to salt and does not grow in natural saline
      environments. Yet many trees are actually exposed to salt stress due to the
      common practice of de-icing of mountain roads in winter, using large amounts of
      NaCl. To help develop strategies for an appropriate use of reproductive seed
      material on reforestation sites, ensuring better chances of seedling survival in
      salt-affected areas, we have studied the responses of young spruce seedlings to
      salt treatments. The specific aim of the work was to identify the optimal salt
      stress biomarkers in Picea abies, using as experimental material seedlings
      obtained by germination of seeds with origin in seven populations from the
      Romanian Carpathian Mountains. These responses included general, conserved
      reactions such as the accumulation of ions and different osmolytes in the
      seedlings needles, reduction in photosynthetic pigments levels, or activation of
      antioxidant systems. Although changes in the contents of different compounds
      involved in these reactions can be associated to the degree of stress affecting
      the plants, we propose that the (decreasing) levels of total phenolics or total
      carotenoids and the (increasing) levels of Na+ or K+ ions in Picea abies needles,
      should be considered as the most reliable and useful biomarkers for salt stress
      in this species. They all show very high correlation with the intensity of salt
      stress, independently of the genetic background of the seeds parental population,
      and relatively easy, quantitative assays are available to determine their
      concentrations, requiring simple equipment and little amount of plant material. 

PMID- 26287689
TI  - Correction: Do Nobel Laureates Create Prize-Winning Networks? An Analysis of
      Collaborative Research in Physiology or Medicine.

PMID- 26287690
TI  - Salmonella enterica Serovar Szentes, a Rare Serotype Causing a 9-Month Outbreak
      in 2013 and 2014 in Switzerland.
AB  - During the summer of 2013, an increase of Salmonella enterica ssp. enterica
      serovar Szentes isolates from human clinical cases was registered by the Swiss
      National Centre for Enteropathogenic Bacteria and Listeria. In the course of the
      ensuing 9 months, 18 isolates originating from 13 patients and from one food
      sample were collected. Of the 13 human cases, 10 (77%) were female. The patients'
      ages ranged from 27 to 83 years (median age 49 years). Pulsed-field gel
      electrophoresis (PFGE) performed with XbaI, and multilocus sequence typing (MLST)
      were used to type the strains. PFGE as well as MLST showed the strains as
      indistinguishable. The PFGE pattern and MLST sequence type (ST427) were identical
      to those of Salmonella enterica serovar Szentes isolated in previous years (2002
      2013) from sporadic cases in Switzerland and Germany. The increased isolation
      frequency continued for 6 months after the detection of Salmonella Szentes in
      sprouts. No common food exposure could be established. Due to lack of information
      on the potential food source, further investigations were not possible. The
      outbreak of this unusual serotype was detected because of its temporal
      clustering. 

PMID- 26287688
TI  - Iron Deficiency Impairs Intra-Hepatic Lymphocyte Mediated Immune Response.
AB  - Hepatic expression of iron homeostasis genes and serum iron parameters predict
      the success of immunosuppression withdrawal following clinical liver
      transplantation, a phenomenon known as spontaneous operational tolerance. In
      experimental animal models, spontaneous liver allograft tolerance is established
      through a process that requires intra-hepatic lymphocyte activation and deletion.
      Our aim was to determine if changes in systemic iron status regulate intra
      hepatic lymphocyte responses. We used a murine model of lymphocyte-mediated acute
      liver inflammation induced by Concanavalin A (ConA) injection employing mice fed
      with an iron-deficient (IrDef) or an iron-balanced diet (IrRepl). While the mild
      iron deficiency induced by the IrDef diet did not significantly modify the steady
      state immune cell repertoire and systemic cytokine levels, it significantly
      dampened inflammatory liver damage after ConA challenge. These findings were
      associated with a marked decrease in T cell and NKT cell activation following
      ConA injection in IrDef mice. The decreased liver injury observed in IrDef mice
      was independent from changes in the gut microflora, and was replicated employing
      an iron specific chelator that did not modify intra-hepatic hepcidin secretion.
      Furthermore, low-dose iron chelation markedly impaired the activation of isolated
      T cells in vitro. All together, these results suggest that small changes in iron
      homeostasis can have a major effect in the regulation of intra-hepatic lymphocyte
      mediated responses. 

PMID- 26287692
TI  - Mechanisms Involved in the Anti-inflammatory and Vascular Effects of Iberis amara
      Extract.
AB  - The anti-inflammatory potential and vasoprotective effects of an Iberis amara
      extract in a rat model of arthritis were investigated. I. amara, or bitter
      candytuft, has long been known for its anti-inflammatory properties on account of
      its active constituents, including cucurbitacins, kaempferol, and sinapic acid.
      The present study was intended to explore more in depth its anti-inflammatory
      activity in both acute (carrageenan rat paw edema) and chronic (adjuvant-induced
      arthritis) models of inflammation. An extract of I. amara dose-dependently
      reduced the extent of edema in both models. In the chronic model, this was
      associated with a reduction in the inflammation mediators tumor necrosis factor
      alpha, interleukin-1beta, and prostaglandin E2 and in the antioxidant biomarkers
      malondialdehyde and total nitrate/nitrite. Because arthritis was reported both
      clinically and experimentally to contribute towards different vascular
      complications, it was of interest to study ex vivo the sensitivity of aortic
      rings in our experimental setup towards norepinephrine, acetylcholine, and sodium
      nitroprusside. The aortic rings from arthritic rats showed no change in
      sensitivity to norepinephrine, but showed a reduced sensitivity to sodium
      nitroprusside and acetylcholine. To show whether the treatment of the arthritis
      would restore endothelial function, I. amara extract was shown to markedly reduce
      the reactivity to norepinephrine, but not to appreciably affect the reactivity
      towards sodium nitroprusside and it had a tendency towards normalizing reactivity
      to acetylcholine. Taken collectively, the findings imply an improvement in
      endothelial function and lend support to the use of the extract in rheumatic
      inflammatory conditions to help safeguard the integrity of the endothelium and
      reduce the risk of vascular complications. 

PMID- 26287693
TI  - GPR18 Inhibiting Amauromine and the Novel Triterpene Glycoside Auxarthonoside
      from the Sponge-Derived Fungus Auxarthron reticulatum.
AB  - The marine sponge-derived fungus Auxarthron reticulatum produces the cannabinoid
      receptor antagonist amauromine (1). Recultivation of the fungus to obtain further
      amounts for more detailed pharmacological evaluation of 1 additionally yielded
      the novel triterpene glycoside auxarthonoside (2), bearing, in nature, a rather
      rare sugar moiety, i.e., N-acetyl-6-methoxy-glucosamine. Amauromine (1), which
      inhibited cannabinoid CB1 receptors (Ki 0.178 uM) also showed antagonistic
      activity at the cannabinoid-like orphan receptor GPR18 (IC50 3.74 uM). The
      diketopiperazine 1 may thus serve as a lead structure for the development of more
      potent and selective GPR18 antagonists, which are required to study the orphan
      receptor's potential as a new drug target. Despite the execution of many
      biological assays, to date, no bioactivity could be found for auxarthonoside (2).

PMID- 26287691
TI  - Improved Estimation of Cardiac Function Parameters Using a Combination of
      Independent Automated Segmentation Results in Cardiovascular Magnetic Resonance
      Imaging.
AB  - This work aimed at combining different segmentation approaches to produce a
      robust and accurate segmentation result. Three to five segmentation results of
      the left ventricle were combined using the STAPLE algorithm and the reliability
      of the resulting segmentation was evaluated in comparison with the result of each
      individual segmentation method. This comparison was performed using a supervised
      approach based on a reference method. Then, we used an unsupervised statistical
      evaluation, the extended Regression Without Truth (eRWT) that ranks different
      methods according to their accuracy in estimating a specific biomarker in a
      population. The segmentation accuracy was evaluated by estimating six cardiac
      function parameters resulting from the left ventricle contour delineation using a
      public cardiac cine MRI database. Eight different segmentation methods, including
      three expert delineations and five automated methods, were considered, and
      sixteen combinations of the automated methods using STAPLE were investigated. The
      supervised and unsupervised evaluations demonstrated that in most cases, STAPLE
      results provided better estimates than individual automated segmentation methods.
      Overall, combining different automated segmentation methods improved the
      reliability of the segmentation result compared to that obtained using an
      individual method and could achieve the accuracy of an expert. 

PMID- 26287694
TI  - Reproduction of the Medicinal Plant Pelargonium sidoides via Somatic
      Embryogenesis.
AB  - The medicinal plant Pelargonium sidoides DC. (Geraniaceae) was traditionally used
      for the treatment of the common cold and cough in South Africa. Today an aequous
      ethanolic root extract from this plant is approved for the treatment of acute
      bronchitis and is globally marketed also as an immunostimulant. The increasing
      demand of the plant material for the industrial production indicates the need of
      new effective methods for the propagation of P. sidoides. Here we report somatic
      embryogenesis and in vitro plantlet regeneration from somatic cells of
      inflorescence shoots and petioles of P. sidoides. A one-week cultivation of
      explants in media containing different concentrations of thidiazuron (1, 2.2, 3,
      and 4 mg/L) followed by a cultivation period without phytohormones resulted in
      the induction of somatic embryos within 2-4 weeks. After 2-4 months, the embryos
      generated roots and could be transferred into a greenhouse, where flower
      formation took place and the development of seeds occurred with high germination
      rates. The root umckalin concentration, determined by high-performance thin-layer
      chromatography, was comparable to that of seed-cultivated plants (100 +/- 6 vs.
      113 +/- 10 ug umckalin/g dried roots). For the first time, direct somatic
      embryogenesis has been established as an appropriate cultivation method for P.
      sidoides plants used as raw material in the pharmaceutical industry. Moreover,
      genetically identical plants (chemical races) can be easily generated by this
      procedure.

PMID- 26287695
TI  - Influence of Processing on the Content of Toxic Carboxyatractyloside and
      Atractyloside and the Microbiological Status of Xanthium sibiricum Fruits
      (Cang'erzi).
AB  - The dried ripe fruits of Xanthium sibiricum (Cang'erzi) are used in traditional
      Chinese medicine for the treatment of nasal congestion, nasal discharge, allergic
      rhinitis, sinusitis, and wind-cold headaches. Carboxyatractyloside and
      atractyloside are important constituents of the fruits because these diterpenoid
      glycosides are responsible for their toxicity. In order to evaluate procedures
      for reducing the amount of the more toxic carboxyatractyloside, the fruits were
      dried and heated with different methods. Carboxyatractyloside and atractyloside
      were analysed by a new reversed-phase high-performance liquid chromatographic
      method using liquid chromatography-diode array detector-tandem mass spectrometry
      analysis. The results revealed that temperature and drying methods have a strong
      influence on the content of carboxyatractyloside and atractyloside. Fruits which
      were treated at higher temperatures showed a lower content of
      carboxyatractyloside and an increased content of atractyloside, which is 50 times
      less toxic. This indicates that the roasting process can reduce toxicity
      effectively. The microbiological colonisation of Xanthium fruits is also reduced
      by roasting and by drying above 100  degrees C. For the safe use of Cang'erzi,
      the effect of processing should be monitored and analysis of carboxyatractyloside
      and atractyloside should be obligatory in quality control. 

PMID- 26287696
TI  - Solubility of Carbon Dioxide in Pentaerythritol Hexanoate: Molecular Dynamics
      Simulation of a Refrigerant-Lubricant Oil System.
AB  - We have investigated the solubility and the solvation structure between a
      refrigerant (carbon dioxide, CO2) and a lubricant oil (pentaerythritol hexanoate,
      PEC6) by molecular dynamics simulations. First, to investigate the solubility, we
      calculated the vapor-liquid equilibrium pressure. The chemical potential of the
      liquid phase and the gas phase were calculated, and the equilibrium state was
      obtained from the crossing point of these chemical potentials. The equilibrium
      pressures agreed well with experimental data over a wide range of temperatures
      and mole fractions of CO2. Second, the solvation structure was also investigated
      on a molecular scale. We found the following characteristics. First, the tails of
      the lubricant oil are relatively rigid inside the ester groups but flexible
      beyond. Second, CO2 molecules barely enter the lubricant core as delimited by the
      ester groups. Third, the double-bonded oxygen atoms of the ester groups are good
      sorption sites for CO2. Fourth, only a few CO2 molecules are attached to more
      than one carbonyl oxygen simultaneously. Finally, there is also significant
      unspecific sorption of CO2 in the alkane tail region. These results indicate that
      increasing the size of the rigid lubricant core would probably decrease the
      solubility, whereas increasing the number of polar groups would increase it. 

PMID- 26287697
TI  - Chemopreventive effects of pequi oil (Caryocar brasiliense Camb.) on
      preneoplastic lesions in a mouse model of hepatocarcinogenesis.
AB  - Pequi (Caryocar brasiliense Camb.), a fruit from Brazil's central region, was
      evaluated for its chemopreventive effects on preneoplastic liver lesions induced
      by the carcinogen diethylnitrosamine (DEN) in mice. BALB/c mice, 14 days of age,
      received an intraperitoneal injection at 10 ug/g of DEN. The mice received either
      of two doses of pequi oil (100 or 400 mg/kg) daily from the age of 30 days and
      were killed at the age of 189 days. Stereological parameters, including the
      volume density (Vv) and the total volume (Vtot) of the lesions (preneoplastic and
      adenomas), were measured and the expression of cytokeratins CK8/18 was evaluated.
      The total volume of lesions and adenomas was reduced by 51% in the group treated
      with the carcinogen and 400 mg/kg of pequi oil administered daily by an oral
      gavage for 25 consecutive weeks. In addition, some mice in this group did not
      develop lesions. Among the remaining preneoplastic lesions in this group, the
      number of remodelled profiles increased by 2.4-fold in the 400-mg pequi oil
      treated mice relative to the 100-mg-treated mice. Our results show that pequi oil
      exerts a hepatoprotective effect against DEN-induced development of preneoplastic
      lesions and adenoma in mice and the potential for its use in the prevention of
      liver cancer.

PMID- 26287698
TI  - Real-time in-vivo microscopic imaging of the cervix using confocal laser
      endomicroscopy: preliminary observations and feasibility study.
AB  - Confocal laser endomicroscopy (CLE) enables in-vivo, real-time, imaging of
      tissues with a micron-scale resolution through a fiber optic probe. CLE could be
      a valuable tool for the detection and characterization of suspicious (dysplastic)
      areas on the uterine cervix in a minimally invasive manner. This study evaluates
      the technical feasibility and safety of CLE on the cervix. The study also aims to
      create a preliminary iconography of normal and dysplastic squamous and columnar
      cervical epithelium. In-vivo CLE was performed on nine patients scheduled for a
      cervical loop electric excision procedure for high-grade superficial
      intraepithelial lesions. The CLE images were compared with standard hematoxylin
      and eosin analysis of loop electric excision procedure specimens. The
      histopathological diagnosis on the surgical specimen was established as per
      standard of care. CLE images were then reviewed by pathologists to point out
      specific histopathological features. pCLE of the exocervix and the transformation
      zone was performed successfully on seven out of nine patients. Uninterpretable
      images were obtained in two other cases: one using the AlveoFlex and one using
      the GastroFlex UHD after the application of acetic acid 2%. A total of 82.5% of
      the sequences recorded with the GastroFlex were suitable for interpretation. No
      adverse event or complications occurred. CLE enables proper in-vivo imaging of
      healthy and dysplastic cervical tissue. Images correlate well with the
      histopathological features established through traditional histology. Future
      blinded prospective analysis will determine the reliability of the real-time
      diagnosis and its potential use in the assessment and treatment of cervical
      lesions.

PMID- 26287699
TI  - Search engine secrets: Finding reliable health information.

PMID- 26287700
TI  - A passion for compassion.

PMID- 26287703
TI  - Promoting a perception of quietness on a telemetry unit.

PMID- 26287704
TI  - A peer mentorship program boosts student retention.

PMID- 26287708
TI  - Making a change to pediatric nursing.

PMID- 26287709
TI  - Patient education series. Latex allergy.

PMID- 26287710
TI  - Launching your professional career.

PMID- 26287711
TI  - What to do about sexually inappropriate behavior in patients with dementia.

PMID- 26287712
TI  - Nurse's guide to surgical drain removal.

PMID- 26287713
TI  - Ensuring milieu safety in a forensic psychiatric unit.

PMID- 26287714
TI  - Pasteurella infection: An unexpected complication after hip arthroplasty.

PMID- 26287715
TI  - What's stiff-person syndrome?

PMID- 26287716
TI  - Resources for scleroderma.

PMID- 26287717
TI  - Gastrointestinal medications.

PMID- 26287719
TI  - Synthesis and Incorporation of Unnatural Amino Acids To Probe and Optimize
      Protein Bioconjugations.
AB  - The utilization of unnatural amino acids (UAAs) in bioconjugations is ideal due
      to their ability to confer a degree of bioorthogonality and specificity. In order
      to elucidate optimal conditions for the preparation of bioconjugates with UAAs,
      we synthesized 9 UAAs with variable methylene tethers (2-4) and either an azide,
      alkyne, or halide functional group. All 9 UAAs were then incorporated into green
      fluorescent protein (GFP) using a promiscuous aminoacyl-tRNA synthetase. The
      different bioconjugations were then analyzed for optimal tether length via
      reaction with either a fluorophore or a derivatized resin. Interestingly, the
      optimal tether length was found to be dependent on the type of reaction. Overall,
      these findings provide a better understanding of various parameters that can be
      optimized for the efficient preparation of bioconjugates. 

PMID- 26287721
TI  - The Role of Fast Cell Cycle Analysis in Pediatric Brain Tumors.
AB  - Cell cycle analysis by flow cytometry has not been adequately studied in
      pediatric brain tumors. We investigated the value of a modified rapid (within 6
      min) cell cycle analysis protocol for the characterization of malignancy of
      pediatric brain tumors and for the differentiation of neoplastic from
      nonneoplastic tissue for possible intraoperative application. We retrospectively
      studied brain tumor specimens from patients treated at our institute over a 5
      year period. All tumor samples were histopathologically verified before flow
      cytometric analysis. The histopathological examination of permanent tissue
      sections was the gold standard. There were 68 brain tumor cases. All tumors had
      significantly lower G0/G1 and significantly higher S phase and mitosis fractions
      than normal brain tissue. Furthermore low-grade tumors could be differentiated
      from high-grade tumors. DNA aneuploidy was detected in 35 tumors. A correlation
      between S phase fraction and Ki-67 index was found in medulloblastomas and
      anaplastic ependymomas. Rapid cell cycle analysis by flow cytometry is a
      promising method for the identification of neoplastic tissue intraoperatively.
      Low-grade tumors could be differentiated from high-grade tumors. Thus, cell cycle
      analysis can be a valuable adjunct to the histopathological evaluation of
      pediatric brain tumors, whereas its intraoperative application warrants further
      investigation. 

PMID- 26287722
TI  - Importance of teeth in maintaining the morphology of the adult mandible in
      humans.
AB  - Edentulism can negatively affect both masticatory performance and dietary intake
      by altering the patterns of biomechanical stress and strain, which in turn
      modifies the morphology of the different regions of the mandible. The
      morphological changes in the mandible caused by these stressors are unknown when
      comparing mandibles across varying dentition states. This study investigated
      differences in the morphology of human mandibles across various states of the
      dentition. In total, 498 mandibles of individuals between 20 and 80 yr of age at
      death were sourced from the Raymond A. Dart Collection of Human Skeletons. These
      included fully dentate (n = 95), partially edentulous (n = 333), and fully
      edentulous (n = 70) mandibles. Twelve linear anthropometric measurements of the
      mandible were derived from digitized landmarks located on its external surface.
      Data analysis included geometric morphometrics and multivariate analyses.
      Compared with dentate and partially edentulous mandibles, fully edentulous
      mandibles showed a shorter alveolar height (-0.4 mm), a shorter mandibular body
      length (-4 mm), a larger gonial angle (+4 degrees ), a more obtuse mental angle
      (+4.7 degrees ), a broader bicondylar width (+3.8 mm), and a taller ramus height
      (+1.6 mm). Thus, edentulous states are associated with an altered mandibular
      morphology, which may result from a reduction in jaw function.

PMID- 26287723
TI  - The rpb2 gene represents a viable alternative molecular marker for the analysis
      of environmental fungal communities.
AB  - Although the commonly used internal transcribed spacer region of rDNA (ITS) is
      well suited for taxonomic identification of fungi, the information on the
      relative abundance of taxa and diversity is negatively affected by the multicopy
      nature of rDNA and the existence of ITS paralogues. Moreover, due to high
      variability, ITS sequences cannot be used for phylogenetic analyses of unrelated
      taxa. The part of single-copy gene encoding the second largest subunit of RNA
      polymerase II (rpb2) was thus compared with first spacer of ITS as an alternative
      marker for the analysis of fungal communities in spruce forest topsoil, and their
      applicability was tested on a comprehensive mock community. In soil, rpb2
      exhibited broad taxonomic coverage of the entire fungal tree of life including
      basal fungal lineages. The gene exhibited sufficient variation for the use in
      phylogenetic analyses and taxonomic assignments, although it amplifies also
      paralogues. The fungal taxon spectra obtained with rbp2 region and ITS1
      corresponded, but sequence abundance differed widely, especially in the basal
      lineages. The proportions of OTU counts and read counts of major fungal groups
      were close to the reality when rpb2 was used as a molecular marker while they
      were strongly biased towards the Basidiomycota when using the ITS primers
      ITS1/ITS4. Although the taxonomic placement of rbp2 sequences is currently more
      difficult than that of the ITS sequences, its discriminative power, quantitative
      representation of community composition and suitability for phylogenetic analyses
      represent significant advantages. 

PMID- 26287724
TI  - Autologous Serum Eye Drops Accelerate Epithelial Healing After LASEK.

PMID- 26287725
TI  - Reductively Responsive Hydrogel Nanoparticles with Uniform Size, Shape, and
      Tunable Composition for Systemic siRNA Delivery in Vivo.
AB  - To achieve the great potential of siRNA based gene therapy, safe and efficient
      systemic delivery in vivo is essential. Here we report reductively responsive
      hydrogel nanoparticles with highly uniform size and shape for systemic siRNA
      delivery in vivo. "Blank" hydrogel nanoparticles with high aspect ratio were
      prepared using continuous particle fabrication based on PRINT (particle
      replication in nonwetting templates). Subsequently, siRNA was conjugated to
      "blank" nanoparticles via a disulfide linker with a high loading ratio of up to
      18 wt %, followed by surface modification to enhance transfection. This
      fabrication process could be easily scaled up to prepare large quantity of
      hydrogel nanoparticles. By controlling hydrogel composition, surface
      modification, and siRNA loading ratio, siRNA conjugated nanoparticles were highly
      tunable to achieve high transfection efficiency in vitro. FVII-siRNA conjugated
      nanoparticles were further stabilized with surface coating for in vivo siRNA
      delivery to liver hepatocytes, and successful gene silencing was demonstrated at
      both mRNA and protein levels. 

PMID- 26287726
TI  - Changes in body mass index in long-term childhood cancer survivors.
AB  - BACKGROUND: Previous studies have reported changes in the body mass index (BMI)
      with time in childhood cancer survivors (CCSs) during follow-up. The limitations
      of these studies include that they described only a subgroup of survivors or used
      questionnaires with self-reported heights and weights. The goal of this study was
      to examine BMI in a large cohort of long-term CCSs and relate this to the BMI at
      diagnosis, age, sex, tumor type, treatment, and endocrine defects. METHODS: All
      patients treated for childhood cancer at the Emma Children's Hospital/Academic
      Medical Center between 1966 and 1996 who had survived for at least 5 years were
      eligible for inclusion. For 893 CCSs with a mean follow-up of 14.9 years, the BMI
      at the late effects outpatient clinic was compared with the BMI for the general
      Dutch population. RESULTS: For girls, an increased prevalence of obesity was
      found. Risk factors for developing a high BMI at follow-up were a younger age and
      a high BMI at diagnosis and treatment with cranial radiotherapy. A significantly
      increased prevalence of severe underweight was found in all adult subgroups
      except for females aged 26 to 45 years. An association was found between a low
      BMI at diagnosis and a low BMI at follow-up. No treatment-related variables could
      be related to changes in BMI. CONCLUSIONS: The BMI at diagnosis is one of the
      most important predictors for the BMI at follow-up, and this suggests an
      important genetic or environmental cause. Adult CCSs are at high risk for
      developing severe underweight at follow-up. Future studies should focus on the
      causes and clinical consequences of underweight.

PMID- 26287727
TI  - Pax3 and Pax7 interact reciprocally and regulate the expression of cadherin-7
      through inducing neuron differentiation in the developing chicken spinal cord.
AB  - Pax3 and Pax7 are closely related transcription factors that are widely expressed
      in the developing nervous system and somites. In the CNS, both genes are
      expressed in the dorsal part of the neural tube during development. Pax3 and Pax7
      are involved in the sonic hedgehog (Shh) signaling pathway and are inhibited by
      Shh overexpression. The present study confirms in vivo that Pax3 overexpression
      represses the expression of Pax7, whereas Pax7 overexpression endogenously
      enhances and ectopically induces the expression of Pax3 in the developing chicken
      spinal cord. Overexpression of Pax3 and Pax7 represses the endogenous expression
      of cadherin-7, a member of the cadherin family of morphogenetic genes, and
      induces its ectopic expression. The present study also shows that overexpression
      of Pax3 and Pax7 changes the fate and morphology of cells in the neuroepithelial
      layer and induces the expression of postmitotic neuronal markers. We show that
      both Pax3 and Pax7 promote the differentiation of neural progenitor cells into
      neurons. Furthermore, the downregulation of Pax3 and Pax7 with specific shRNAs
      results in apoptosis in the developing spinal cord. Collectively, these results
      suggest that the transcription factors Pax3 and Pax7 play important roles in
      regulating morphogenesis and cell differentiation in the developing spinal cord.

PMID- 26287728
TI  - Clonal CD8+ T Cell Persistence and Variable Gene Usage Bias in a Human
      Transplanted Hand.
AB  - Immune prophylaxis and treatment of transplanted tissue rejection act
      indiscriminately, risking serious infections and malignancies. Although animal
      data suggest that cellular immune responses causing rejection may be rather
      narrow and predictable based on genetic background, there are only limited data
      regarding the clonal breadth of anti-donor responses in humans after allogeneic
      organ transplantation. We evaluated the graft-infiltrating CD8+ T lymphocytes in
      skin punch biopsies of a transplanted hand over 178 days. Profiling of T cell
      receptor (TCR) variable gene usage and size distribution of the infiltrating
      cells revealed marked skewing of the TCR repertoire indicating oligoclonality,
      but relatively normal distributions in the blood. Although sampling limitation
      prevented complete assessment of the TCR repertoire, sequencing further
      identified 11 TCR clonal expansions that persisted through varying degrees of
      clinical rejection and immunosuppressive therapy. These 11 clones were limited to
      three TCR beta chain variable (BV) gene families. Overall, these data indicate
      significant oligoclonality and likely restricted BV gene usage of alloreactive
      CD8+ T lymphocytes, and suggest that changes in rejection status are more due to
      varying regulation of their activity or number rather than shifts in the clonal
      populations in the transplanted organ. Given that controlled animal models
      produce predictable BV usage in T lymphocytes mediating rejection, understanding
      the determinants of TCR gene usage associated with rejection in humans may have
      application in specifically targeted immunotherapy. 

PMID- 26287730
TI  - A comparison between index of entropy and catastrophe theory methods for mapping
      groundwater potential in an arid region.
AB  - In this study, index of entropy and catastrophe theory methods were used for
      demarcating groundwater potential in an arid region using weighted linear
      combination techniques in geographical information system (GIS) environment. A
      case study from Badra area in the eastern part of central of Iraq was analyzed
      and discussed. Six factors believed to have influence on groundwater occurrence
      namely elevation, slope, aquifer transmissivity and storativity, soil, and
      distance to fault were prepared as raster thematic layers to facility integration
      into GIS environment. The factors were chosen based on the availability of data
      and local conditions of the study area. Both techniques were used for computing
      weights and assigning ranks vital for applying weighted linear combination
      approach. The results of application of both modes indicated that the most
      influential groundwater occurrence factors were slope and elevation. The other
      factors have relatively smaller values of weights implying that these factors
      have a minor role in groundwater occurrence conditions. The groundwater potential
      index (GPI) values for both models were classified using natural break
      classification scheme into five categories: very low, low, moderate, high, and
      very high. For validation of generated GPI, the relative operating characteristic
      (ROC) curves were used. According to the obtained area under the curve, the
      catastrophe model with 78 % prediction accuracy was found to perform better than
      entropy model with 77 % prediction accuracy. The overall results indicated that
      both models have good capability for predicting groundwater potential zones.

PMID- 26287729
TI  - Glyphosate Use Predicts ADHD Hospital Discharges in the Healthcare Cost and
      Utilization Project Net (HCUPnet): A Two-Way Fixed-Effects Analysis.
AB  - There has been considerable international study on the etiology of rising mental
      disorders, such as attention-deficit hyperactivity disorder (ADHD), in human
      populations. As glyphosate is the most commonly used herbicide in the world, we
      sought to test the hypothesis that glyphosate use in agriculture may be a
      contributing environmental factor to the rise of ADHD in human populations. State
      estimates for glyphosate use and nitrogen fertilizer use were obtained from the
      U.S. Geological Survey (USGS). We queried the Healthcare Cost and Utilization
      Project net (HCUPNET) for state-level hospitalization discharge data in all
      patients for all-listed ADHD from 2007 to 2010. We used rural-urban continuum
      codes from the USDA-Economic Research Service when exploring the effect of
      urbanization on the relationship between herbicide use and ADHD. Least squares
      dummy variable (LSDV) method and within method using two-way fixed effects was
      used to elucidate the relationship between glyphosate use and all-listed ADHD
      hospital discharges. We show that a one kilogram increase in glyphosate use, in
      particular, in one year significantly positively predicts state-level all-listed
      ADHD discharges, expressed as a percent of total mental disorders, the following
      year (coefficient = 5.54E-08, p<.01). A study on the effect of urbanization on
      the relationship between glyphosate and ADHD indicates that the relationship is
      marginally significantly positive after multiple comparison correction only in
      urban U.S. counties (p<.025). Furthermore, total glyphosate use is strongly
      positively associated with total farm use of nitrogen fertilizers from 1992 to
      2006 (p<.001). We present evidence from the biomedical research literature of a
      plausible link among glyphosate, nitrogen dysbiosis and ADHD. Glyphosate use is a
      significant predictor of state hospitalizations for all-listed ADHD hospital
      discharges, with the effect concentrated in urban U.S. counties. This effect is
      seen even after controlling for individual state characteristics, strong
      correlations over time, and other significant associations with ADHD in the
      literature. We draw upon the econometric results to propose unique mechanisms,
      borrowing principles from soil and atmospheric sciences, for how glyphosate-based
      herbicides may be contributing to the rise of ADHD in all populations. 

PMID- 26287731
TI  - Factors Associated with Inconsistent Condom Use among Men Who Have Sex with Men
      in Cambodia.
AB  - BACKGROUND: Compared to the general population, men who have sex with men (MSM)
      are at greater risk for HIV and less understood due to their more hidden and
      stigmatized nature. Moreover, the discrepancy in findings in the literature
      merits further investigations in MSM populations from different cultures and
      settings. We therefore conducted this study to explore factors associated with
      inconsistent condom use among high-risk MSM in Cambodia. METHODS: This cross
      sectional study was conducted in 2014 among 367 MSM randomly selected from
      Battembang and Siem Reap using a two-stage cluster sampling method. A structured
      questionnaire was used for face-to-face interviews to collect information on
      characteristics of respondents, HIV testing history, self-perception of HIV risk,
      substance use, sexual behaviors, mental disorders, and HIV knowledge.
      Multivariable logistic regression analysis was performed to identify factors
      independently associated with inconsistent condom use. RESULTS: On average, 62.3%
      of respondents reported that they always used condoms over the past three months.
      The rates varied with types of sexual partners; the proportion of respondents who
      reported always using condoms was 55.1%, 64.2%, 75.9%, 73.0%, 78.1%, and 70.3%,
      for sexual partners who were girlfriends, boyfriends, female sex workers, male
      sex workers, female clients, or male clients, respectively. After adjustment,
      inconsistent condom use was significantly associated with age of >=25 (AOR =
      1.77, 95% CI = 1.09-2.86), self-rated quality of life as good or very good (AOR =
      4.37, 95% CI = 1.79-5.67), self-perception of higher HIV risk compared to the
      general population (AOR = 2.37, 95% CI = 1.35-4.17), illicit drug use in the past
      three months (AOR = 5.76, 95% CI = 1.65-10.09), and reported consistent lubricant
      use when selling anal sex to men in the past three months (AOR = 2.85, 95% CI =
      1.07-8.12). CONCLUSIONS: We found risky sexual behaviors to be considerably high
      among MSM in this study, especially among those who used illicit drugs or were
      older than 25. HIV education and social marketing should be expanded and
      specifically designed for MSM to better educate on the increased risk of HIV with
      unprotected anal sex and illicit drug use as risk factors, and the importance of
      the use of both condoms and lubricant during anal intercourse.

PMID- 26287732
TI  - TNF Induction of NF-kappaB RelB Enhances RANKL-Induced Osteoclastogenesis by
      Promoting Inflammatory Macrophage Differentiation but also Limits It through
      Suppression of NFATc1 Expression.
AB  - TNF induces bone loss in common bone diseases by promoting osteoclast formation
      directly and indirectly, but it also limits osteoclast formation by inducing
      expression of NF-kappaB p100. Osteoclast precursors (OCPs) are derived from M1
      (inflammatory) and M2 (resident) macrophages. However, it is not known if TNF
      stimulates or limits osteoclast formation through regulation of M1 or M2
      differentiation or if RelB, a partner of p100, is involved. To investigate these
      questions, we treated bone marrow cells (BMCs) with M-CSF alone or in combination
      with TNF to enrich for OCPs, which we called M-OCPs and T-OCPs, respectively. We
      found that TNF switched CD11b+F4/80+ M-OCPs from Ly6C-Gr1- M2 to Ly6C+Gr1-CD11c+
      and Ly6C-Gr1-CD11c+ M1 cells. RANKL induced osteoclast formation from both
      Ly6C+Gr1- and Ly6C-Gr1- T-OCPs, but only from Ly6C+Gr1- M-OCPs, which formed
      significantly fewer osteoclasts than T-OCPs. Importantly, Ly6C+Gr1- cells from
      both M- and T-OCPs have increased expression of the M1 marker genes, iNOS, TNF,
      IL-1beta and TGFbeta1, compared to Ly6C-Gr1- cells, and Ly6C-Gr1- cells from T
      OCPs also have increased expression of iNOS and TGFbeta1 compared to cells from M
      OCPs. Both RANKL and TNF increased RelB mRNA expression. TNF significantly
      increased RelB protein levels, but RANKL did not because it also induced RelB
      proteasomal degradation. TNF inhibited RANKL-induced NFATc1 mRNA expression and
      osteoclast formation from M-OCPs, but not from T-OCPs, and it did not induce
      Ly6C+Gr1-CD11c+ or Ly6C-Gr1-CD11c+ M1 macrophages from RelB-/- BMCs. Furthermore,
      overexpression of RelB in M-OCPs reduced RANKL-induced osteoclast formation and
      NFATc1 mRNA expression, but it increased TNF-induced OC formation without
      affecting NFATc1 levels. Thus, TNF induction of RelB directly mediates terminal
      osteoclast differentiation independent of NFATc1 and limits RANKL-induced
      osteoclastogenesis by inhibiting NFATc1 activation. However, the dominant role of
      TNF is to expand the OCP pool by switching the differentiation of M-CSF-induced
      M2 to M1 macrophages with enhanced osteoclast forming potential. Strategies to
      degrade RelB could prevent TNF-induced M2/M1 switching and reduce osteoclast
      formation. 

PMID- 26287733
TI  - The Axl-Regulating Tumor Suppressor miR-34a Is Increased in ccRCC but Does Not
      Correlate with Axl mRNA or Axl Protein Levels.
AB  - BACKGROUND: High expression of the receptor tyrosine kinase Axl is associated
      with poor prognosis in patients with Renal Cell Carcinoma (RCC), the most common
      malignancy of the kidney. The miR-34a has been shown to directly regulate Axl in
      cancer cells. The miR-34a is a mediator of p53-dependent tumor suppression, and
      low expression of miR-34a has been associated with worse prognosis in several
      cancers. Our aim was to elucidate whether miR-34a or the other members of the miR
      34 family (miR-34b/c) regulate Axl in RCC. METHODOLOGY AND RESULTS: Using western
      blot, flow cytometry, and RT-qPCR, we showed that Axl mRNA and protein are
      downregulated in 786-O cells by miR-34a and miR-34c but not by miR-34b. A
      luciferase reporter assay demonstrated direct interaction between the Axl 3' UTR
      and miR-34a and miR-34c. The levels of miR-34a/b/c were measured in tumor tissue
      in a cohort of 198 RCC patients, and the levels of miR-34a were found to be
      upregulated in clear cell RCC (ccRCC) tumors, but not associated with patient
      outcome. Neither of the miR-34 family members correlated with Axl mRNA, soluble
      Axl protein in serum, nor with immunohistochemistry of Axl in tumor tissue. In
      addition, we measured mRNA levels of a known miR-34a target, HNF4A, and found the
      HNF4A levels to be decreased in ccRCC tumors, but unexpectedly correlated
      positively rather than negatively with miR-34a. CONCLUSIONS: Although miR-34a and
      miR-34c can regulate Axl expression in vitro, our data indicates that the miR-34
      family members are not the primary regulators of Axl expression in RCC.

PMID- 26287736
TI  - Biomimetic Nanoporous Anodic Alumina Distributed Bragg Reflectors in the Form of
      Films and Microsized Particles for Sensing Applications.
AB  - In this study, we produce for the first time biomimetic films and microsized
      particles based on nanoporous anodic alumina distributed Bragg reflectors (NAA
      DBRs) by a rational galvanostatic pulse-anodization approach. These biomimetic
      photonic structures can feature a broad range of vivid bright colors, which can
      be tuned across the UV-visible spectrum by engineering their nanoporous structure
      through different anodization parameters. The effective medium of NAA-DBRs films
      is systematically assessed as a function of the anodization period, the
      anodization temperature, and the current density ratio by reflectometric
      interference spectroscopy (RIfS). This analysis makes it possible to establish
      the most sensitive structure toward changes in its effective medium.
      Subsequently, specific detection of vitamin C molecules is demonstrated. The
      obtained results reveal that NAA-DBRs with optimized structure can achieve a low
      limit of detection for vitamin C molecules as low as 20 nM, a sensitivity of
      227+/-4 nm MUM(-1), and a linearity of 0.9985. Finally, as proof of concept, we
      developed a new photonic nanomaterial based on NAA-DBR microsized particles,
      which could provide new opportunities to produce microsized photonic analytical
      tools.

PMID- 26287735
TI  - Comparison of the Toxicokinetics and Bioaccumulation Potential of Mercury and
      Polychlorinated Biphenyls in Goldfish (Carassius auratus).
AB  - Both mercury (Hg) and polychlorinated biphenyls (PCBs) demonstrate food web
      biomagnification in aquatic ecosystems, yet their toxicokinetics have not been
      simultaneously contrasted within a common fish species. This study quantifies
      uptake and elimination rates of Hg and PCBs in goldfish. Fish were exposed to
      contaminated food containing PCBs and Hg to determine dietary chemical
      assimilation efficiencies (AEs) and elimination coefficients (ktot). To test
      first-order kinetics, three exposure regimes were established by varying the
      proportion of contaminated fish incorporated into the food. Dietary AEs were 98
      +/- 10, 75 +/- 12, and 40 +/- 9% for MeHg, THg, and PCBs, respectively. The ktot
      values were 0.010 +/- 0.003 and 0.010 +/- 0.002 day(-1) for THg and MeHg,
      respectively. No significant differences were found in ktot among the dosing
      levels for either THg or MeHg, confirming that Hg elimination is a first-order
      process. For PCB, ktot ranged from 0.007 to 0.022 day(-1) and decreased with an
      increase in hydrophobicity. This study revealed that Hg had an AE higher than
      that of PCBs, while the ktot of Hg was similar to those measured for the most
      hydrophobic PCBs. We conclude that Hg has a bioaccumulation potential in goldfish
      118% higher than the highest PCB BMF observed for congeners with a log KOW of >7.

PMID- 26287737
TI  - The effect of potential supramolecular-bond promoters on the DNA-interacting
      abilities of copper-terpyridine compounds.
AB  - Three copper(ii) coordination compounds have been prepared from three different
      2,2':6',2''-terpyridine-based ligands, which have been selected to investigate
      the potential role of supramolecular interactions on the DNA-interacting and
      cytotoxicity properties of the corresponding metal complexes. Hence, the ligands
      4'-((naphthalen-2-yl)methoxy)-2,2':6',2''-terpyridine () and 4'-((1H
      benzo[d]imidazol-2-yl)methoxy)-2,2':6',2''-terpyridine () have been synthesized
      from commercially-available 4'-chloro-2,2':6',2''-terpyridine (), and their
      copper(ii) complexes have been obtained by reaction with copper(ii) nitrate. The
      DNA-interacting abilities of the corresponding compounds [Cu()(H2O)(NO3)2] (),
      [Cu()(NO3)(H2O)](NO3)(MeOH) () and [Cu()(NO3)(H2O)](NO3) () have been
      investigated using different techniques, and cytotoxicity assays with several
      cancer cell lines have revealed interesting features, viz. the more efficient
      complex is , which although it does not act as a DNA cleaver, displays the most
      effective DNA-interacting and cytotoxic properties, compared to and . 

PMID- 26287738
TI  - Isotretinoin Exposure and Risk of Celiac Disease.
AB  - BACKGROUND: Isotretinoin (13-cis retinoic acid) is a metabolite of vitamin A and
      has anti-inflammatory and immunoregulatory effects; however, a recent publication
      by DePaolo et al. demonstrated that in the presence of IL-15, retinoic acid can
      act as an adjuvant and promote inflammation against dietary proteins. OBJECTIVE:
      To evaluate the risk of overt and latent celiac disease (CD) among users of
      isotretinoin. MATERIAL AND METHODS: Medical records of patients from 1995 to 2011
      who had a mention of isotretinoin in their records (N = 8393) were searched for
      CD diagnosis using ICD-09CM codes. Isotretinoin exposure was compared across
      overt CD patients and their age- and gender-matched controls from the same pool.
      To evaluate the risk of latent CD with isotretinoin exposure, patients were
      overlapped with a community-based list of patients with waste serum samples that
      were tested for CD serology, excluding those with overt CD (2006-2011).
      Isotretinoin exposure was defined as the use of isotretinoin prior to CD
      diagnosis or serology. RESULTS: Of 8393 patients, 25 had a confirmed CD
      diagnosis. Compared to matched controls (N = 75), isotretinoin exposure was not
      significantly different between overt CD patients versus controls (36% versus
      39%, respectively; P = 0.712). Likewise, latent CD defined as positive serology
      was not statistically different between isotretinoin exposed (N = 506) versus non
      exposed (N = 571) groups (1.8% versus 1.4%, respectively; P = 0.474).
      CONCLUSIONS: There was no association between isotretinoin use and risk of either
      overt or latent CD.

PMID- 26287739
TI  - NRCMS capitation reform and effect evaluation in Pudong New Area of Shanghai.
AB  - The Rural Cooperative Medical Scheme (RCMS) had played an important role in
      guaranteeing the acquisition of basic medical healthcare of China's rural
      populations, being an innovative model of the medical insurance system for so
      many years here in China. Following the boom and bust of RCMS, the central
      government rebuilt the New Rural Cooperative Medical Scheme (NRCMS) in 2003
      across the whole country. Shanghai, one of the developed cities in China, has
      developed its RCMS and NRCMS as an advanced and exemplary representative of
      Chinese rural health insurance. But in the past 10 years, its NRCMS has
      encountered such challenges as a spiral of medical expenditures and a decrease of
      insurance participants. Previous investigations showed that the capitation and
      general practitioner (GP) system had great effect on medical cost containment.
      Thus, the capitation reform combined with GP system reform of NRCMS, based on a
      system design, was implemented in Pudong New Area of Shanghai as of 1 August
      2012. The aim of the current investigation was to present how the reform was
      designed and implemented, evaluating its effect by analyzing the data acquired
      from 12 months before and after the reform. This was an empirical study; we made
      a conceptual design of the reform to be implemented in Pudong New Area. Most data
      were derived from the institution-based surveys and supplemented by a
      questionnaire survey, qualitative interviews and policy document analysis. We
      found that most respondents held an optimistic attitude towards the reform. We
      employed a structure-process-outcome evaluation index system to evaluate the
      effect of the reform, finding that the growth rate of the insured population's
      total medical costs and NRCMS funds slowed down significantly after the reform;
      that the total medical expenditure of the insured rural population decreased by
      3.60%; and that the total expenditure of NRCMS decreased by 3.99%. The capitation
      was found to help the medical staff build active cost control consciousness.
      Approximately 2.3% of the outpatients flowed to the primary hospitals from the
      secondary hospitals; and farmers' annual medical burden was relieved to a certain
      degree. Meanwhile, it did not affect farmers' utilization and benefits of
      healthcare. However, further reform still faces new challenges: The capitation
      reform should be well combined with the primary healthcare system to realize the
      "dual gatekeeper" of GPs; a variety of payment methods should be mixed on the
      basis of capitation to avoid possible mistakes by one single approach; and the
      supervision of medical institutions should be strengthened. A long-term follow-up
      study need to be carried out to evaluate the effects of the capitation reform so
      as to improve the design of the program. Copyright (c) 2015 John Wiley & Sons,
      Ltd. 

PMID- 26287740
TI  - E3 ubiquitin ligase gene CMPG1-V from Haynaldia villosa L. contributes to powdery
      mildew resistance in common wheat (Triticum aestivum L.).
AB  - Powdery mildew is one of the most devastating wheat fungal diseases. A diploid
      wheat relative, Haynaldia villosa L., is highly resistant to powdery mildew, and
      its genetic resource of resistances, such as the Pm21 locus, is now widely used
      in wheat breeding. Here we report the cloning of a resistance gene from H.
      villosa, designated CMPG1-V, that encodes a U-box E3 ubiquitin ligase. Expression
      of the CMPG1-V gene was induced in the leaf and stem of H. villosa upon
      inoculation with Blumeria graminis f. sp. tritici (Bgt) fungus, and the presence
      of Pm21 is essential for its rapid induction of expression. CMPG1-V has conserved
      key residues for E3 ligase, and possesses E3 ligase activity in vitro and in
      vivo. CMPG1-V is localized in the nucleus, endoplasmic reticulum, plasma membrane
      and partially in trans-Golgi network/early endosome vesicles. Transgenic wheat
      over-expressing CMPG1-V showed improved broad-spectrum powdery mildew resistance
      at seedling and adult stages, associated with an increase in expression of
      salicylic acid-responsive genes, H2 O2 accumulation, and cell-wall protein cross
      linking at the Bgt infection sites, and the expression of CMPG1-V in H. villosa
      was increased when treated with salicylic acid, abscisic acid and H2 O2 . These
      results indicate the involvement of E3 ligase in defense responses to Bgt fungus
      in wheat, particularly in broad-spectrum disease resistance, and suggest
      association of reactive oxidative species and the phytohormone pathway with CMPG1
      V-mediated powdery mildew resistance. 

PMID- 26287741
TI  - Predictors of Compassion Fatigue and Compassion Satisfaction in Acute Care
      Nurses.
AB  - PURPOSE: To examine compassion fatigue and compassion satisfaction in acute care
      nurses across multiple specialties in a hospital-based setting. DESIGN: A cross
      sectional electronic survey design was used to collect data from direct care
      nurses in a 700-bed, quaternary care, teaching facility in the southwestern
      United States. METHODS: A total of 491 direct care registered nurses completed a
      survey measuring their professional quality of life (burnout, secondary traumatic
      stress, and compassion satisfaction). Analysis was conducted to assess for
      differences between demographics, specialties, job satisfaction, and intent to
      leave their current position. FINDINGS: Significant predictors of burnout
      included lack of meaningful recognition, nurses with more years of experience,
      and nurses in the "Millennial" generation (ages 21-33 years). Receiving
      meaningful recognition, higher job satisfaction, nurses in the "Baby Boomer"
      generation (ages 50-65 years), and nurses with fewer years of experience
      significantly predicted compassion satisfaction. No significant differences were
      noted across nurse specialties, units, or departments. CONCLUSIONS: This study
      adds to the literature the impact meaningful recognition may have on compassion
      satisfaction and fatigue. Our findings provide a potential explanation for the
      lack of retention of nurses in the millennial generation who leave their
      positions with limited years of experience. Based on our research, meaningful
      recognition may increase compassion satisfaction, positively impact retention,
      and elevate job satisfaction. CLINICAL RELEVANCE: Compassion fatigue in nurses
      has clear implications for nursing retention and the quality of care.
      Organizations willing to invest in reducing compassion fatigue have the potential
      to improve financial savings by reducing turnover and adverse events associated
      with burnout.

PMID- 26287742
TI  - Glucose Metabolism Disorders, HIV and Antiretroviral Therapy among Tanzanian
      Adults.
AB  - INTRODUCTION: Millions of HIV-infected Africans are living longer due to long
      term antiretroviral therapy (ART), yet little is known about glucose metabolism
      disorders in this group. We aimed to compare the prevalence of glucose metabolism
      disorders among HIV-infected adults on long-term ART to ART-naive adults and HIV
      negative controls, hypothesizing that the odds of glucose metabolism disorders
      would be 2-fold greater even after adjusting for possible confounders. METHODS:
      In this cross-sectional study conducted between October 2012 and April 2013,
      consecutive adults (>18 years) attending an HIV clinic in Tanzania were enrolled
      in 3 groups: 153 HIV-negative controls, 151 HIV-infected, ART-naive, and 150 HIV
      infected on ART for >= 2 years. The primary outcome was the prevalence of glucose
      metabolism disorders as determined by oral glucose tolerance testing. We compared
      glucose metabolism disorder prevalence between each HIV group vs. the control
      group by Fisher's exact test and used multivariable logistic regression to
      determine factors associated with glucose metabolism disorders. RESULTS: HIV
      infected adults on ART had a higher prevalence of glucose metabolism disorders
      (49/150 (32.7%) vs.11/153 (7.2%), p<0.001) and frank diabetes mellitus (27/150
      (18.0%) vs. 8/153 (5.2%), p = 0.001) than HIV-negative adults, which remained
      highly significant even after adjusting for age, gender, adiposity and
      socioeconomic status (OR = 5.72 (2.78-11.77), p<0.001). Glucose metabolism
      disorders were significantly associated with higher CD4+ T-cell counts. Awareness
      of diabetes mellitus was <25%. CONCLUSIONS: HIV-infected adults on long-term ART
      had 5-fold greater odds of glucose metabolism disorders than HIV-negative
      controls but were rarely aware of their diagnosis. Intensive glucose metabolism
      disorder screening and education are needed in HIV clinics in sub-Saharan Africa.
      Further research should determine how glucose metabolism disorders might be
      related to immune reconstitution.

PMID- 26287744
TI  - Correction: Spatial Assortment of Mixed Propagules Explains the Acceleration of
      Range Expansion.

PMID- 26287743
TI  - Development of Genomic Microsatellite Markers in Carthamus tinctorius L.
      (Safflower) Using Next Generation Sequencing and Assessment of Their Cross
      Species Transferability and Utility for Diversity Analysis.
AB  - BACKGROUND: Safflower (Carthamus tinctorius L.), an Asteraceae member, yields
      high quality edible oil rich in unsaturated fatty acids and is resilient to dry
      conditions. The crop holds tremendous potential for improvement through concerted
      molecular breeding programs due to the availability of significant genetic and
      phenotypic diversity. Genomic resources that could facilitate such breeding
      programs remain largely underdeveloped in the crop. The present study was
      initiated to develop a large set of novel microsatellite markers for safflower
      using next generation sequencing. PRINCIPAL FINDINGS: Low throughput genome
      sequencing of safflower was performed using Illumina paired end technology
      providing ~3.5X coverage of the genome. Analysis of sequencing data allowed
      identification of 23,067 regions harboring perfect microsatellite loci. The
      safflower genome was found to be rich in dinucleotide repeats followed by tri-,
      tetra-, penta- and hexa-nucleotides. Primer pairs were designed for 5,716 novel
      microsatellite sequences with repeat length >= 20 bases and optimal flanking
      regions. A subset of 325 microsatellite loci was tested for amplification, of
      which 294 loci produced robust amplification. The validated primers were used for
      assessment of 23 safflower accessions belonging to diverse agro-climatic zones of
      the world leading to identification of 93 polymorphic primers (31.6%). The
      numbers of observed alleles at each locus ranged from two to four and mean
      polymorphism information content was found to be 0.3075. The polymorphic primers
      were tested for cross-species transferability on nine wild relatives of
      cultivated safflower. All primers except one showed amplification in at least two
      wild species while 25 primers amplified across all the nine species. The UPGMA
      dendrogram clustered C. tinctorius accessions and wild species separately into
      two major groups. The proposed progenitor species of safflower, C. oxyacantha and
      C. palaestinus were genetically closer to cultivated safflower and formed a
      distinct cluster. The cluster analysis also distinguished diploid and tetraploid
      wild species of safflower. CONCLUSION: Next generation sequencing of safflower
      genome generated a large set of microsatellite markers. The novel markers
      developed in this study will add to the existing repertoire of markers and can be
      used for diversity analysis, synteny studies, construction of linkage maps and
      marker-assisted selection.

PMID- 26287745
TI  - Cytoplasmatic and Nuclear YAP1 and pYAP1 Staining in Urothelial Bladder Cancer.
AB  - INTRODUCTION: Yes-associated protein 1 (YAP1), the nuclear effector of the Hippo
      pathway, plays an important role in many tumor entities. We evaluated staining
      and clinical significance of YAP1 and phosphorylated YAP1 (pYAP1) in urothelial
      bladder cancer (BCA). MATERIALS AND METHODS: We used a tissue micorarray with
      samples of patients with muscle-invasive bladder cancer (MIBC, n = 192), non
      muscle-invasive bladder cancer (NMIBC, n = 192) and normal urothelial bladder
      tissue (CTRL, n = 38) to determine the immunhistochemical staining of YAP1 and
      pYAP1. Cytoplasmatic and nuclear levels were evaluated. The t test was used for
      comparative analysis. Overall survival and progression-free survival were
      evaluated by Kaplan-Meier estimates and the Cox proportional hazard regression
      model. RESULTS: Nuclear YAP1 as well as cytoplasmatic pYAP1 levels were higher in
      CTRL than in BCA, whereby both--NMIBC and MIBC--had lower levels than CTRL. Among
      patients with MIBC, cytoplasmatic YAP1 and pYAP1 staining decreased with advanced
      stage. YAP1 and pYAP1 staining did not correlate with the recurrence rate,
      progression-free, cancer-specific or overall survival. CONCLUSIONS:
      Immunhistochemical staining and subcellular localization of YAP1 and pYAP1 are
      different for BCA, NMIBC, MIBC and CTRL, indicating that the Hippo pathway is
      involved in urothelial carcinogenesis.

PMID- 26287747
TI  - Unraveling the Function of FTO Variants.

PMID- 26287748
TI  - New DTCA Guidance--Enough to Empower Consumers?

PMID- 26287746
TI  - FTO Obesity Variant Circuitry and Adipocyte Browning in Humans.
AB  - BACKGROUND: Genomewide association studies can be used to identify disease
      relevant genomic regions, but interpretation of the data is challenging. The FTO
      region harbors the strongest genetic association with obesity, yet the
      mechanistic basis of this association remains elusive. METHODS: We examined
      epigenomic data, allelic activity, motif conservation, regulator expression, and
      gene coexpression patterns, with the aim of dissecting the regulatory circuitry
      and mechanistic basis of the association between the FTO region and obesity. We
      validated our predictions with the use of directed perturbations in samples from
      patients and from mice and with endogenous CRISPR-Cas9 genome editing in samples
      from patients. RESULTS: Our data indicate that the FTO allele associated with
      obesity represses mitochondrial thermogenesis in adipocyte precursor cells in a
      tissue-autonomous manner. The rs1421085 T-to-C single-nucleotide variant disrupts
      a conserved motif for the ARID5B repressor, which leads to derepression of a
      potent preadipocyte enhancer and a doubling of IRX3 and IRX5 expression during
      early adipocyte differentiation. This results in a cell-autonomous developmental
      shift from energy-dissipating beige (brite) adipocytes to energy-storing white
      adipocytes, with a reduction in mitochondrial thermogenesis by a factor of 5, as
      well as an increase in lipid storage. Inhibition of Irx3 in adipose tissue in
      mice reduced body weight and increased energy dissipation without a change in
      physical activity or appetite. Knockdown of IRX3 or IRX5 in primary adipocytes
      from participants with the risk allele restored thermogenesis, increasing it by a
      factor of 7, and overexpression of these genes had the opposite effect in
      adipocytes from nonrisk-allele carriers. Repair of the ARID5B motif by CRISPR
      Cas9 editing of rs1421085 in primary adipocytes from a patient with the risk
      allele restored IRX3 and IRX5 repression, activated browning expression programs,
      and restored thermogenesis, increasing it by a factor of 7. CONCLUSIONS: Our
      results point to a pathway for adipocyte thermogenesis regulation involving
      ARID5B, rs1421085, IRX3, and IRX5, which, when manipulated, had pronounced pro
      obesity and anti-obesity effects. (Funded by the German Research Center for
      Environmental Health and others.).

PMID- 26287749
TI  - The Vernacular of Risk--Rethinking Direct-to-Consumer Advertising of
      Pharmaceuticals.

PMID- 26287751
TI  - The New Director of "the Spermatogonial Niche": Introducing the Peritubular
      Macrophage.
AB  - In this issue of Cell Reports, DeFalco et al. (2015) characterize a novel
      macrophage population associated with the peritubular lamina of mouse testes.
      These macrophages may create a niche not for the self-renewal of stem cells but
      rather the induction of their differentiation.

PMID- 26287752
TI  - Nanometric distance measurements between Mn(ii)DOTA centers.
AB  - Pulse electron-electron double resonance (PELDOR) is a versatile technique for
      probing the structures and functions of complex biological systems. Despite the
      recent interest in high-spin metal-ions for high field/frequency applications,
      PELDOR measurements of Mn(ii) remain relatively underexplored. Here we present
      Mn(ii)-Mn(ii) PELDOR distance measurements at 94 GHz on polyproline II (PPII)
      helices doubly spin-labeled with Mn(ii)DOTA, which are distinguished by their
      small zero-field interaction. The measured Mn-Mn distances and distribution
      profiles were in good agreement with the expected values from molecular models.
      Additional features in the frequency-domain spectra became apparent at certain
      combinations of detect and pump frequencies. Spin-Hamiltonian calculations showed
      that they likely arose from contributions from the pseudo-secular component of
      the dipolar interaction that were found to be non-negligible for Mn(ii)DOTA.
      However, the influence of the pseudo-secular component on the distance
      distribution profiles apparently was limited. The results show the potential of
      Mn(ii)DOTA spin labels for high-field PELDOR distance measurements in proteins
      and other biological systems. 

PMID- 26287750
TI  - Acute intermittent hypoxia induced phrenic long-term facilitation despite
      increased SOD1 expression in a rat model of ALS.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative
      disease characterized by motor neuron death. Since most ALS patients succumb to
      ventilatory failure from loss of respiratory motor neurons, any effective ALS
      treatment must preserve and/or restore breathing capacity. In rats over
      expressing mutated super-oxide dismutase-1 (SOD1(G93A)), the capacity to increase
      phrenic motor output is decreased at disease end-stage, suggesting imminent
      ventilatory failure. Acute intermittent hypoxia (AIH) induces phrenic long-term
      facilitation (pLTF), a form of spinal respiratory motor plasticity with potential
      to restore phrenic motor output in clinical disorders that compromise breathing.
      Since pLTF requires NADPH oxidase activity and reactive oxygen species (ROS)
      formation, it is blocked by NADPH oxidase inhibition and SOD mimetics in normal
      rats. Thus, we hypothesized that SOD1(G93A) (mutant; MT) rats do not express AIH
      induced pLTF due to over-expression of active mutant superoxide dismutase-1. AIH
      induced pLTF and hypoglossal (XII) LTF were assessed in young, pre-symptomatic
      and end-stage anesthetized MT rats and age-matched wild-type littermates.
      Contrary to predictions, pLTF and XII LTF were observed in MT rats at all ages;
      at end-stage, pLTF was actually enhanced. SOD1 levels were elevated in young and
      pre-symptomatic MT rats, yet superoxide accumulation in putative phrenic motor
      neurons (assessed with dihydroethidium) was unchanged; however, superoxide
      accumulation significantly decreased at end-stage. Thus, compensatory mechanisms
      appear to maintain ROS homoeostasis until late in disease progression, preserving
      AIH-induced respiratory plasticity. Following intrathecal injections of an NADPH
      oxidase inhibitor (apocynin; 600 MUM; 12 MUL), pLTF was abolished in pre
      symptomatic, but not end-stage MT rats, demonstrating that pLTF is NADPH oxidase
      dependent in pre-symptomatic, but NADPH oxidase independent in end-stage MT rats.
      Mechanisms preserving/enhancing the capacity for pLTF in MT rats are not known.

PMID- 26287753
TI  - The efficacy of plantar stimulation on human balance control.
AB  - AIM: The aim of this study was to evaluate the body sway using firm, foam, and
      firm textured surfaces on 17 young adults. METHOD: Displacement of center of
      pressure (CoP), anteroposterior velocity (VA/P), and mediolateral velocity (VM/L)
      were measured. DATA: The data showed a significant decrease of CoP, VA/P, and
      VM/L between support surfaces and vision. RESULTS: The results showed that,
      differently from the firm and foam, the textured surface is able to increase the
      plantar feedback to maintaining postural control.

PMID- 26287754
TI  - Return-to-work challenges following a work-related mild TBI: The injured worker
      perspective.
AB  - PRIMARY OBJECTIVE: To explore how individuals with work-related mild traumatic
      brain injury (wrMTBI) experience return-to-work (RTW) processes when returning to
      the workplace where the injury occurred. DESIGN: RTW experiences were explored
      using in-depth interviews and an inductive analytic approach. Qualitative
      analysis guided by the research question moved through phases of line-by-line and
      thematic coding through which categories and the interaction between categories
      emerged. PARTICIPANTS: Twelve workers diagnosed with a wrMTBI reported on their
      RTW experiences following wrMTBIs that occurred 3-5 years prior to the time of
      the interview. MAIN OUTCOMES AND RESULTS: Participants perceived employer and
      workers' compensation factors as profoundly influencing their RTW experiences.
      Participants consistently reported that employers and workers' compensation
      representatives had an inadequate understanding of wrMTBI sequelae. Six of 12
      participants were re-injured following their wrMTBI, with three of these injuries
      occurring at work. CONCLUSION: Employers, co-workers and workers' compensation
      representatives should be aware of wrMTBI sequelae so injured workers can receive
      appropriate supports and both stigmatization and re-injury can be mitigated.
      Greater attention to the structural and social elements of workplace and
      compensation environments could inform strategies to break down barriers to
      successful return-to-work following a wrMTBI.

PMID- 26287755
TI  - Psychosis, psychedelic substance misuse and head injury: A case report and 23
      year follow-up.
AB  - BACKGROUND: This study describes the case of a 57 year old gentleman with a
      previous severe brain injury who developed a severe psychotic disorder 19 years
      after the injury. This appears to have been precipitated by heavy psychedelic
      substance use, including cannabis, salvia divinorum, ketamine, LSD, cocaine and
      DMT amongst others. The psychosis remained in the absence of drug intoxication
      and was associated with prominent apathy, lack of concern and abulia. CASE STUDY:
      This study discusses the heavy psychedelic substance misuse possibly potentiating
      a transition to psychosis in this individual. Little work has been undertaken in
      this area as substance misuse has traditionally been an exclusion criteria for
      investigating psychosis in this patient group. CONCLUSIONS: It is suggested that
      psychedelic substance misuse should be investigated as a risk factor for
      psychotic illness in patients with brain injury, as this case clearly suggests.

PMID- 26287758
TI  - Melatonin and selenium reduce plasma cytokine and brain oxidative stress levels
      in diabetic rats.
AB  - BACKGROUND: Hyperglycaemia-induced progression of brain and erythrocyte oxidative
      injuries might be modulated by melatonin and selenium as potent antioxidants. The
      present study was conducted to explore whether melatonin and selenium protect
      against diabetic brain and erythrocyte oxidative stress levels in streptozotocin
      (STZ)-induced diabetic rats. MATERIALS AND METHODS: Seventy rats were equally
      divided into seven groups. The first and second groups were used as untreated and
      placebo treated controls. The third group was treated with STZ to induce
      diabetes. The fourth and sixth groups received 10 mg kg(-1) melatonin. The fifth
      and seventh groups were treated with 1.5 mg kg(-1) selenium (sodium selenite).
      The sixth and seventh groups were treated with STZ administered with melatonin
      and selenium as described for the fourth and fifth groups. RESULTS: Brain and
      erythrocyte lipid peroxidation levels and plasma IL-1beta and IL-4 levels were
      high in the STZ group, although they were low in melatonin and selenium
      treatments. Decreased glutathione peroxidase, reduced glutathione, total
      antioxidant status, vitamins A and vitamin E values in brain and erythrocyte of
      STZ group were increased by melatonin and selenium treatments. DISCUSSION:
      Melatonin and selenium induced protective effects against diabetes-induced brain
      and erythrocyte oxidative injuries through regulation of the antioxidant level
      and cytokine production.

PMID- 26287759
TI  - Does anticholinergics drug burden relate to global neuro-disability outcome
      measures and length of hospital stay?
AB  - PRIMARY OBJECTIVE: To assess the relationship between disability, length of stay
      (LOS) and anticholinergic burden (ACB) with people following acquired brain or
      spinal cord injury. RESEARCH DESIGN: A retrospective case note review assessed
      total rehabilitation unit admission. METHODS AND PROCEDURES: Assessment of 52
      consecutive patients with acquired brain/spinal injury and neuropathy in an in
      patient neuro-rehabilitation unit of a UK university hospital. Data analysed
      included: Northwick Park Dependency Score (NPDS), Rehabilitation complexity Scale
      (RCS), Functional Independence Measure and Functional Assessment Measure FIM-FAM
      (UK version 2.2), LOS and ACB. Outcome was different in RCS, NPDS and FIM-FAM
      between admission and discharge. MAIN OUTCOMES AND RESULTS: A positive change was
      reported in ACB results in a positive change in NPDS, with no significant effect
      on FIM-FAM, either Motor or Cognitive, or on the RCS. Change in ACB correlated to
      the length of hospital stay (regression correlation = -6.64; SE = 3.89). There
      was a significant harmful impact of increase in ACB score during hospital stay,
      from low to high ACB on NPDS (OR = 9.65; 95% CI = 1.36-68.64) and FIM-FAM Total
      scores (OR = 0.03; 95% CI = 0.002-0.35). CONCLUSIONS: There was a statistically
      significant correlation of ACB and neuro-disability measures and LOS amongst this
      patient cohort.

PMID- 26287756
TI  - Pilot feasibility of an mHealth system for conducting ecological momentary
      assessment of mood-related symptoms following traumatic brain injury.
AB  - OBJECTIVE: This study assessed pilot feasibility and validity of a mobile health
      (mHealth) system for tracking mood-related symptoms after traumatic brain injury
      (TBI). DESIGN: A prospective, repeated measures design was used to assess
      compliance with daily ecological momentary assessments (EMA) conducted via a
      smartphone application over an 8-week period. METHODS: An mHealth system was
      developed specifically for individuals with TBI and utilized previously validated
      tools for depressive and anxiety symptoms (Patient Health Questionnaire-9,
      Generalized Anxiety Disorder-7). Feasibility was assessed in 20 community
      dwelling adults with TBI via an assessment of compliance, satisfaction and
      usability of the smartphone applications. The authors also developed and
      implemented a clinical patient safety management mechanism for those endorsing
      suicidality. RESULTS: Participants correctly completed 73.4% of all scheduled
      assessments, demonstrating good compliance. Daily assessments took <2 minutes to
      complete. Participants reported high satisfaction with smartphone applications
      (6.3 of 7) and found them easy to use (6.2 of 7). Comparison of assessments
      obtained via telephone-based interview and EMA demonstrated high correlations (r
      = 0.81-0.97), supporting the validity of conducting these assessments via
      smartphone application in this population. CONCLUSIONS: EMA conducted via
      smartphone demonstrates initial feasibility among adults with TBI and presents
      numerous opportunities for long-term monitoring of mood-related symptoms in real
      world settings.

PMID- 26287760
TI  - Effects of local administration of allogenic adipose tissue-derived mesenchymal
      stem cells on functional recovery in experimental traumatic brain injury.
AB  - OBJECTIVE: Traumatic brain injury (TBI) is the leading cause of mortality and
      morbidity in paediatric patients after the first year of life. The aim of this
      study was to evaluate effects of locally administered allogeneic mesenchymal stem
      cells (MSC), in the acute period after a TBI. METHODOLOGY: MSC were isolated from
      peritoneal fat of healthy rats, expanded in vitro and labelled with the green
      fluorescent protein. Rats were placed in one of three experimental groups: (1)
      CONTROL: TBI, (2) IP-CONTROL: TBI + local saline and (3) IP-Treat: TBI + 2 *
      10(5) MSC 24 hours after receiving a moderate, unilateral, controlled cortical
      impact. Motor and cognitive behavioural tests were performed to evaluate
      functional recovery. Histological examination and immunohistochemistry were used
      to identify cell distribution. MAIN RESULTS: Improved performance was found on
      motor tests in the MSC-treated group compared to control groups. MSC were found
      in the perilesional area and their number decreased with time after
      transplantation. MSC treatment increased the cell density in the hippocampus (CA3
      pyramidal cells and granule cells in the dentate gyrus) and enhanced neurogenesis
      in this area. CONCLUSION: MSC cell therapy resulted in better recovery of motor
      function compared with the control group. This cellular therapy might be
      considered for patients suffering from TBI.

PMID- 26287761
TI  - Insomnia symptoms and behavioural health symptoms in veterans 1 year after
      traumatic brain injury.
AB  - OBJECTIVE: Insomnia and behavioural health symptoms 1 year after traumatic brain
      injury (TBI) were examined in a clinical sample representative of veterans who
      received inpatient treatment for TBI-related issues within the Veterans Health
      Administration. METHODS: This was a cross-sectional sub-study (n = 112) of the
      Polytrauma Rehabilitation Centres' traumatic brain injury model system programme.
      Prevalence estimates of insomnia, depression, general anxiety, nightmares,
      headache and substance use, stratified by injury severity, were derived.
      Univariate logistic regression was used to examine unadjusted effects for each
      behavioural health problem and insomnia by injury severity. RESULTS: Participants
      were primarily male, < 30 years old and high school educated. Twenty-nine per
      cent met study criteria for insomnia; those with mild TBI were significantly more
      likely to meet criteria (43%) than those with moderate/severe TBI (22%),
      chi(2)(1, n = 112) = 5.088, p <= 0.05. Univariable logistic regression analyses
      revealed depressive symptoms and general anxiety were significantly associated
      with insomnia symptoms after TBI of any severity. Headache and binge drinking
      were significantly inversely related to insomnia symptoms after moderate/severe
      TBI, but not MTBI. CONCLUSIONS: Veterans with history of TBI, of any severity,
      and current insomnia symptoms may be at increased risk for depression and anxiety
      1 year after TBI.

PMID- 26287764
TI  - Mini-Review: Limbal Stem Cells Deficiency in Companion Animals: Time to Give
      Something Back?
AB  - Experimental animals have been used extensively in the goal of developing sight
      saving therapies for humans. One example is the development of transplantation of
      cultured limbal epithelial stem cells (LESC) to restore vision following ocular
      surface injury or disease. With clinical trials of cultured LESC therapy underway
      in humans and a potential companion animal population suffering from similar
      diseases, it is perhaps time to give something back. Comparatively to humans,
      what is known about the healthy limbus and corneal surface physiology of
      companion animals is still very little. Blinding corneal diseases in animals such
      as symblepharon in cats with Feline Herpes Virus-1 infections require a basic
      understanding of the functional companion animal limbus and corneal stem cells.
      Our understanding of many other vision threatening conditions such as scarring of
      the cornea post-inflammation with lymphocytic-plasmacytic infiltrate in dogs (aka
      chronic superficial keratitis) or pigment proliferation with Pigmentary Keratitis
      of Pugs would benefit from a better understanding of the animal cornea in health
      and disease. This is also vital when new therapeutic approaches are considered.
      This review will explore the current challenges and future research directions
      that will be required to increase our understanding of corneal diseases in
      animals and consider the potential development and delivery of cultured stem cell
      therapy to veterinary ocular surface patients.

PMID- 26287763
TI  - A high frequency of BRCA mutations in young black women with breast cancer
      residing in Florida.
AB  - BACKGROUND: Black women are disproportionately affected with triple-negative
      breast cancer and have relatively poor survival. To the authors' knowledge, it is
      not known to what extent differences in the clinical presentation of breast
      cancer between non-Hispanic white women and black women can be accounted for by
      the presence of mutations in the BRCA1 and BRCA2 genes. The authors sought to
      evaluate the frequency of BRCA pathogenic variants in a population-based sample
      of young black women with breast cancer. METHODS: Black women diagnosed with
      invasive breast cancer at age <=50 years from 2009 to 2012 were recruited to the
      study through the Florida Cancer Registry. Participants underwent genetic
      counseling, completed a study questionnaire, and consented to release of their
      medical records. Saliva specimens were collected for BRCA sequencing and large
      rearrangement testing through multiplex ligation-dependent probe amplification.
      RESULTS: A DNA sample was evaluated for 396 women, 49 of whom (12.4%) had a
      mutation in BRCA1 or BRCA2. Eight recurrent mutations accounted for 49% of all
      pathogenic variants. CONCLUSIONS: To the authors' knowledge, the prevalence of
      BRCA mutations among the Florida-based sample of young black women with breast
      cancer in the current study exceeds that previously reported for non-Hispanic
      white women. It is appropriate to recommend BRCA testing in all young black women
      with invasive breast cancer.

PMID- 26287766
TI  - Poly(N-Isopropylacrylamide)-co-Acrylamide Hydrogels for the Controlled Release of
      Bromelain from Agroindustrial Residues of Ananas comosus.
AB  - This works reports the purification of bromelain extracted from Ananas comosus
      industrial residues by ethanol purification, its partial characterization from
      the crude extract as well as the ethanol purified enzyme, and its application
      onto poly(N-isopropylacrylamide)-co-acrylamide hydrogels. Bromelain was recovered
      within the 30-70 % ethanol fraction, which achieved a purification factor of 3.12
      fold, and yielded more than 90 % of its initial activity. The resulting purified
      bromelain contained more than 360 U . mg(-1), with a maximum working temperature
      of 60  degrees C and pH of 8.0. Poly(N-isopropylacrylamide)-co-acrylamide
      hydrogels presented a swelling rate of 125 %, which was capable of loading 56 %
      of bromelain from the solution, and was able to release up to 91 % of the
      retained bromelain. Ethanol precipitation is suitable for bromelain recovery and
      application onto poly(N-isopropylacrylamide)-co-acrylamide hydrogels based on its
      processing time and the applied ethanol prices.

PMID- 26287765
TI  - Risk Factors for Vibrio parahaemolyticus Infection in a Southern Coastal Region
      of China.
AB  - OBJECTIVES: The objectives of the study were to identify dietary and medical risk
      factors for Vibrio parahaemolyticus (VP) infection in the coastal city Shenzhen
      in China. METHODS: In April-October 2012, we conducted a case-control study in
      two hospitals in Shenzhen, China. Laboratory-confirmed VP cases (N = 83) were
      matched on age, sex, and other social factors to healthy controls (N = 249).
      Subjects were interviewed using a questionnaire on medical history; contact with
      seawater; clinical symptoms and outcome; travel history over the past week; and
      dietary history 3 days prior to onset. Laboratory tests were used to culture,
      serotype, and genotype VP strains. We used logistic regression to calculate the
      odds ratios for the association of VP infection with potential risk factors.
      RESULTS: In multivariate analysis, VP infection was associated with having pre
      existing chronic disease (adjusted odds ratio [aOR], 6.0; 95% confidence interval
      [CI], 1.5-23.7), eating undercooked seafood (aOR, 8.0; 95% CI, 1.3-50.4), eating
      undercooked meat (aOR, 29.1; 95% CI, 3.0-278.2), eating food from a street food
      vendor (aOR, 7.6; 95% CI, 3.3-17.6), and eating vegetable salad (aOR, 12.1; 95%
      CI, 5.2-28.2). CONCLUSIONS: Eating raw (undercooked) seafood and meat is an
      important source of VP infection among the study population. Cross-contamination
      of VP in other food (e.g., vegetables and undercooked meat) likely plays a more
      important role. Intervention should be taken to lower the risks of cross
      contamination with undercooked seafood/meat, especially targeted at people with
      low income, transient workers, and people with medical risk factors.

PMID- 26287767
TI  - Suppressive Effect of Dietary Fucoidan on Proinflammatory Immune Response and MMP
      1 Expression in UVB-Irradiated Mouse Skin.
AB  - It is well known that ultraviolet B irradiation leads to dermal inflammation. In
      this study, we found that Mekabu fucoidan suppressed edema, decreased the
      thickness of the prickle cell layer, and decreased matrix metalloproteinase 1 in
      the skin of mice irradiated with ultraviolet B. Moreover, we found that the mean
      level of interferon gamma of Mekabu fucoidan-treated, ultraviolet B-irradiated
      mice (approximately 2.2 ng/mL) was not significantly different from that in
      normal mice (approximately 2.5 ng/mL). In contrast, a significant decrease in the
      mean level of interferon gamma (approximately 1.3 ng/mL) in ultraviolet B
      irradiated control mice was observed compared with that in Mekabu fucoidan
      treated, ultraviolet B-irradiated mice. The mean thickness of the prickle cell
      layer in the skin of Mekabu fucoidan-treated, ultraviolet B-irradiated mice was
      less than that in the ultraviolet B-irradiated control mice. Metalloproteinase 1
      activity was significantly higher in the skin of ultraviolet B-irradiated mice
      than in the skin of untreated, nonirradiated normal mice. Metalloproteinase 1 in
      the skin of ultraviolet B-irradiated, Mekabu fucoidan- or L(+)-ascorbic acid
      (vitamin C)-treated mice was significantly lower than that in the ultraviolet B
      irradiated control mice. Mitigation of the morphological changes in Mekabu
      fucoidan-treated mice was correlated with a decrease in metalloproteinase 1
      levels. These data indicate that Mekabu fucoidan is an effective suppressor of
      inflammation in an ultraviolet B-irradiated mouse model. 

PMID- 26287768
TI  - The elicitor-responsive gene for a GRAS family protein, CIGR2, suppresses cell
      death in rice inoculated with rice blast fungus via activation of a heat shock
      transcription factor, OsHsf23.
AB  - We show that a rice GRAS family protein, CIGR2, is a bonafide transcriptional
      activator, and through this function, targets the B-type heat shock protein
      encoding gene OsHsf23 (Os09g0456800). CIGR2 (Os07g0583600) is an N
      acetylchitooligosaccharide elicitor-responsive gene whose activity, through the
      direct transcriptional control of OsHsf23, is required for mediating
      hypersensitive cell death activation during pathogen infection. RNAi lines of
      CIGR2 and OsHsf23 similarly exhibited the higher level of granulation in the
      epidermal cells of leaf sheath inoculated with an avirulent isolate of rice blast
      fungus. Interestingly, we did not observe altered levels of resistance,
      suggesting that CIGR2 suppresses excessive cell death in the incompatible
      interaction with blast fungus via activation of OsHsf23.

PMID- 26287769
TI  - Graphitic carbon nitride nanosheet@metal-organic framework core-shell
      nanoparticles for photo-chemo combination therapy.
AB  - Recently, nanoscale metal-organic frameworks (NMOFs) have started to be developed
      as a promising platform for bioimaging and drug delivery. On the other hand,
      combination therapies using multiple approaches are demonstrated to achieve much
      enhanced efficacy. Herein, we report, for the first time, core-shell
      nanoparticles consisting of a photodynamic therapeutic (PDT) agent and a MOF
      shell while simultaneously carrying a chemotherapeutic drug for effective
      combination therapy. In this work, core-shell nanoparticles of zeolitic
      imadazolate framework-8 (ZIF-8) as shell embedded with graphitic carbon nitride
      (g-C3N4) nanosheets as core are fabricated by growing ZIF-8 in the presence of g
      C3N4 nanosheets. Doxorubicin hydrochloride (DOX) is then loaded into the ZIF-8
      shell of the core-shell nanoparticles. The combination of the chemotherapeutic
      effects of DOX and the PDT effect of g-C3N4 nanosheets can lead to considerably
      enhanced efficacy. Furthermore, the red fluorescence of DOX and the blue
      fluorescence of g-C3N4 nanosheets provide the additional function of dual-color
      imaging for monitoring the drug release process. 

PMID- 26287770
TI  - Ultrasound validation of Trendelenburg positioning to increase internal jugular
      vein cross-sectional area in chronic dialysis patients.
AB  - BACKGROUND AND AIM: Trendelenburg positioning (TP) is a common approach used
      during internal jugular vein (IJV) cannulation. No evidence indicates that TP
      significantly increases the cross-sectional area (CSA) of the IJV or decreases
      the overlap between the carotid artery (CA) and the IJV in dialysis patients. The
      primary aim of this study was to investigate the effects of the TP on the CSA of
      the right IJV and on its relationship to the CA. METHODS: Thirty-seven
      consecutive hemodialysis patients older than 18 years of age were enrolled. We
      measured the CSA of the right IJV and overlap rate (at end-expiration at the
      level of the cricoid cartilage) between the CA and the IJV in two positions:
      State 0, table flat (no tilt), with the patient in the supine position; State T,
      in which the operating table was tilted to 15 degrees  of TP. RESULTS: Data were
      collected for all of the 37 patients enrolled in the study. The change in CSA and
      overlap between the CA and the IJV from the supine to the TP was not
      significantly different. The CSA was paradoxically decreased in 11 of 37 patients
      when changed from State 0 to State T. CONCLUSIONS: TP does not significantly
      increase the CSA of the right IJV or decrease the overlap between the CA and the
      IJV in dialysis patients. In fact, in some patients, it reduces the CSA.
      Therefore, the use of the TP for IJV cannulation in dialysis patients can no
      longer be supported.

PMID- 26287734
TI  - Salt Stress Induced Changes in the Exoproteome of the Halotolerant Bacterium
      Tistlia consotensis Deciphered by Proteogenomics.
AB  - The ability of bacteria to adapt to external osmotic changes is fundamental for
      their survival. Halotolerant microorganisms, such as Tistlia consotensis, have to
      cope with continuous fluctuations in the salinity of their natural environments
      which require effective adaptation strategies against salt stress. Changes of
      extracellular protein profiles from Tistlia consotensis in conditions of low and
      high salinities were monitored by proteogenomics using a bacterial draft genome.
      At low salinity, we detected greater amounts of the HpnM protein which is
      involved in the biosynthesis of hopanoids. This may represent a novel, and
      previously unreported, strategy by halotolerant microorganisms to prevent the
      entry of water into the cell under conditions of low salinity. At high salinity,
      proteins associated with osmosensing, exclusion of Na+ and transport of
      compatible solutes, such as glycine betaine or proline are abundant. We also
      found that, probably in response to the high salt concentration, T. consotensis
      activated the synthesis of flagella and triggered a chemotactic response neither
      of which were observed at the salt concentration which is optimal for growth. Our
      study demonstrates that the exoproteome is an appropriate indicator of adaptive
      response of T. consotensis to changes in salinity because it allowed the
      identification of key proteins within its osmoadaptive mechanism that had not
      previously been detected in its cell proteome. 

PMID- 26287772
TI  - Adaptation of the AnyBodyTM Musculoskeletal Shoulder Model to the Nonconforming
      Total Shoulder Arthroplasty Context.
AB  - Current musculoskeletal inverse dynamics shoulder models have two limitations to
      use in the context of nonconforming total shoulder arthroplasty (NC-TSA). First,
      the ball and socket glenohumeral (GH) joint simplification avoids any humeral
      head translations. Second, there is no contact at the GH joint to compute the
      contact area and the center of pressure (COP) between the two components of NC
      TSA. In this paper, we adapted the AnyBodyTM shoulder model by introducing
      humeral head translations and contact between the two components of an NC-TSA.
      Abduction in the scapular plane was considered. The main objective of this study
      was to adapt the AnyBodyTM shoulder model to a NC-TSA context and to compare the
      results of our model (translations, COP, contact area, GH joint reaction forces
      (GH-JRFs), and muscular forces) with previous numerical, experimental, and
      clinical studies. Humeral head translations and contact were successfully
      introduced in our adapted shoulder model with strong support for our findings by
      previous studies. 

PMID- 26287771
TI  - Prognostic value of CD44 expression in renal cell carcinoma: a systematic review
      and meta-analysis.
AB  - CD44 is a marker of cancer stem-like cells in renal cell carcinoma (RCC).
      However, the prognostic value of CD44 in RCC remains controversial. This study
      evaluated the correlation of CD44 expression with the clinicopathological
      features of RCC through a meta-analysis. We systematically searched PubMed, ISI
      Web of Science and Embase for relevant studies until February 2015. We collected
      and analysed data on clinical stage, Fuhrman grade, microvascular invasion,
      recurrence, five-year overall survival (OS), disease-specific survival (DSS) and
      disease-free survival (DFS). Twenty studies involving 1672 patients satisfied the
      inclusion criteria. Results showed that high CD44 expression in RCC was a poor
      prognostic marker for five-year OS (RR = 0.69, 95% CI 0.60-0.78) in a fixed
      effects model and for five-year DSS (RR = 0.46, 95% CI 0.27-0.80) and five-year
      DFS (RR = 0.63, 95% CI 0.43-0.93) in a random-effects model. CD44 expression also
      correlated with Furhman grade (RR = 0.61, 95% CI 0.48-0.77), tumour recurrence
      (RR = 7.42, 95% CI 3.74-14.70) and MVI (Microvascular invasion) (RR = 3.63, 95%
      CI 1.97-6.71). This meta-analysis suggests that CD44 is a prognostic marker in
      RCC. High CD44 expression correlates with high Fuhrman grade, recurrence, MVI and
      poor prognosis. 

PMID- 26287773
TI  - Delivery of Breech Presentation at Term Gestation in Canada, 2003-2011.

PMID- 26287774
TI  - Fetoscopic Repair of Meningomyelocele.

PMID- 26287775
TI  - The Sky Is Not Falling, but It Is Severely Drooping for the Specialist
      Obstetrician-Gynecologist.

PMID- 26287776
TI  - Effect of an Exercise Intervention on Gestational Diabetes Mellitus: A Randomized
      Controlled Trial.

PMID- 26287780
TI  - Practice Bulletin Summary No. 152: Emergency Contraception.
AB  - Emergency contraception, also known as postcoital contraception, is therapy used
      to prevent pregnancy after an unprotected or inadequately protected act of sexual
      intercourse. Common indications for emergency contraception include contraceptive
      failure (eg, condom breakage or missed doses of oral contraceptives) and failure
      to use any form of contraception (1-3). Although oral emergency contraception was
      first described in the medical literature in the 1960s, the U.S. Food and Drug
      Administration (FDA) approved the first dedicated product for emergency
      contraception in 1998. Since then, several new products have been introduced.
      Methods of emergency contraception include oral administration of combined
      estrogen-progestin, progestin only, or selective progesterone receptor modulators
      and insertion of a copper intrauterine device (IUD). Many women are unaware of
      the existence of emergency contraception, misunderstand its use and safety, or do
      not use it when a need arises (4-6). The purpose of this Practice Bulletin is to
      review the evidence for the efficacy and safety of available methods of emergency
      contraception and to increase awareness of these methods among obstetrician
      gynecologists and other gynecologic providers. 

PMID- 26287781
TI  - Practice Bulletin Summary No. 153: Nausea and Vomiting of Pregnancy.
AB  - Nausea and vomiting of pregnancy is a common condition that affects the health of
      the pregnant woman and her fetus. It can diminish the woman's quality of life and
      also significantly contributes to health care costs and time lost from work (1,
      2). Because "morning sickness" is common in early pregnancy, the presence of
      nausea and vomiting of pregnancy may be minimized by obstetricians, other
      obstetric providers, and pregnant women and, thus, undertreated (1). Furthermore,
      some women do not seek treatment because of concerns about safety of medications
      (3). Once nausea and vomiting of pregnancy progresses, it can become more
      difficult to control symptoms; treatment in the early stages may prevent more
      serious complications, including hospitalization (4). Mild cases of nausea and
      vomiting of pregnancy may be resolved with lifestyle and dietary changes, and
      safe and effective treatments are available for more severe cases. The woman's
      perception of the severity of her symptoms plays a critical role in the decision
      of whether, when, and how to treat nausea and vomiting of pregnancy. In addition,
      nausea and vomiting of pregnancy should be distinguished from nausea and vomiting
      related to other causes. The purpose of this document is to review the best
      available evidence about the diagnosis and management of nausea and vomiting of
      pregnancy. 

PMID- 26287782
TI  - Committee Opinion Summary No. 638: First-Trimester Risk Assessment for Early
      Onset Preeclampsia.
AB  - Hypertensive disorders with adverse sequelae (including preterm birth, maternal
      morbidity and mortality, and long-term risk of maternal cardiovascular disease)
      complicate 5-10% of pregnancies. Early identification of pregnant women at risk
      of developing early-onset preeclampsia would theoretically allow referral for
      more intensive surveillance or application of preventive therapies to reduce the
      risk of severe disease. In practice, however, the effectiveness of such triage
      would be hindered by the low positive predictive value for early-onset
      preeclampsia reported in the literature. In spite of the modest predictive value
      of first-trimester preeclampsia risk assessment and the lack of data
      demonstrating improved clinical outcomes, commercial tests are being marketed for
      the prediction of preeclampsia in the first trimester. Taking a detailed medical
      history to evaluate for risk factors is currently the best and only recommended
      screening approach for preeclampsia; it should remain the method of screening for
      preeclampsia until studies show that aspirin or other interventions reduce the
      incidence of preeclampsia for women at high risk based on first-trimester
      predictive tests. 

PMID- 26287783
TI  - Committee Opinion Summary No. 639: The Importance of Vital Records and Statistics
      for the Obstetrician-Gynecologist.
AB  - Information from vital records is critical to identify and quantify health
      related issues and to measure progress toward quality improvement and public
      health goals. In particular, maternal and infant mortality serve as important
      indicators of the nation's health, thereby influencing policy development,
      funding of programs and research, and measures of health care quality. Accurate
      and timely documentation of births and deaths is essential to high-quality vital
      statistics. This Committee Opinion describes the process by which births,
      maternal deaths, and fetal deaths are registered; the challenges faced with a
      decentralized reporting system; and the important role for obstetrician
      gynecologists in improving the accuracy, reliability, and timeliness of vital
      records. 

PMID- 26287784
TI  - Committee Opinion Summary No. 640: Cell-Free DNA Screening For Fetal Aneuploidy.
AB  - Noninvasive prenatal screening that uses cell-free DNA from the plasma of
      pregnant women offers tremendous potential as a screening method for fetal
      aneuploidy. A number of laboratories have validated different techniques for the
      use of cell-free DNA as a screening test for fetal aneuploidy. All tests have a
      high sensitivity and specificity for trisomy 18 and trisomy 21, regardless of
      which molecular technique is used. Women whose results are not reported,
      indeterminate, or uninterpretable (a "no call" test result) from cell-free DNA
      screening should receive further genetic counseling and be offered comprehensive
      ultrasound evaluation and diagnostic testing because of an increased risk of
      aneuploidy. Patients should be counseled that cell-free DNA screening does not
      replace the precision obtained with diagnostic tests, such as chorionic villus
      sampling or amniocentesis and, therefore, is limited in its ability to identify
      all chromosome abnormalities. Cell-free DNA screening does not assess risk of
      fetal anomalies such as neural tube defects or ventral wall defects. Patients who
      are undergoing cell-free DNA screening should be offered maternal serum alpha
      fetoprotein screening or ultrasound evaluation for risk assessment. The cell-free
      DNA screening test should not be considered in isolation from other clinical
      findings and test results. Management decisions, including termination of the
      pregnancy, should not be based on the results of the cell-free DNA screening
      alone. Patients should be counseled that a negative cell-free DNA test result
      does not ensure an unaffected pregnancy. Given the performance of conventional
      screening methods, the limitations of cell-free DNA screening performance, and
      the limited data on cost-effectiveness in the low-risk obstetric population,
      conventional screening methods remain the most appropriate choice for first-line
      screening for most women in the general obstetric population. 

PMID- 26287785
TI  - Committee Opinion Summary No. 641: Human Papillomavirus Vaccination.
AB  - Human papillomavirus (HPV) is associated with the development of anogenital
      cancer (including cervical, vaginal, vulvar, penile, and anal), oropharyngeal
      cancer, and genital warts. Human papillomavirus vaccination can significantly
      reduce the incidence of anogenital cancer and genital warts. Despite the benefits
      of HPV vaccines, only approximately one third of girls in the recommended age
      group have received all three vaccines. Compared with other vaccines recommended
      in the same age bracket, HPV vaccination rates in the United States are
      unacceptably low. It is crucial that obstetrician-gynecologists and other
      providers educate parents and patients on the benefits and safety of HPV
      vaccination. The Centers for Disease Control and Prevention and the American
      College of Obstetricians and Gynecologists recommend routine vaccination with HPV
      vaccine for girls and boys. The 9-valent HPV vaccine is recommended by the
      Advisory Committee on Immunization Practices and was licensed by the U.S. Food
      and Drug Administration in December 2014 for girls and boys aged 11-12 years. 

PMID- 26287787
TI  - Practice Bulletin No. 152: Emergency Contraception.
AB  - Emergency contraception, also known as postcoital contraception, is therapy used
      to prevent pregnancy after an unprotected or inadequately protected act of sexual
      intercourse. Common indications for emergency contraception include contraceptive
      failure (eg, condom breakage or missed doses of oral contraceptives) and failure
      to use any form of contraception (). Although oral emergency contraception was
      first described in the medical literature in the 1960s, the U.S. Food and Drug
      Administration (FDA) approved the first dedicated product for emergency
      contraception in 1998. Since then, several new products have been introduced.
      Methods of emergency contraception include oral administration of combined
      estrogen-progestin, progestin only, or selective progesterone receptor modulators
      and insertion of a copper intrauterine device (IUD). Many women are unaware of
      the existence of emergency contraception, misunderstand its use and safety, or do
      not use it when a need arises (). The purpose of this Practice Bulletin is to
      review the evidence for the efficacy and safety of available methods of emergency
      contraception and to increase awareness of these methods among obstetrician
      gynecologists and other gynecologic providers. 

PMID- 26287788
TI  - Practice Bulletin No. 153: Nausea and Vomiting of Pregnancy.
AB  - Nausea and vomiting of pregnancy is a common condition that affects the health of
      the pregnant woman and her fetus. It can diminish the woman's quality of life and
      also significantly contributes to health care costs and time lost from work ().
      Because "morning sickness" is common in early pregnancy, the presence of nausea
      and vomiting of pregnancy may be minimized by obstetricians, other obstetric
      providers, and pregnant women and, thus, undertreated (). Furthermore, some women
      do not seek treatment because of concerns about safety of medications (). Once
      nausea and vomiting of pregnancy progresses, it can become more difficult to
      control symptoms; treatment in the early stages may prevent more serious
      complications, including hospitalization (). Mild cases of nausea and vomiting of
      pregnancy may be resolved with lifestyle and dietary changes, and safe and
      effective treatments are available for more severe cases. The woman's perception
      of the severity of her symptoms plays a critical role in the decision of whether,
      when, and how to treat nausea and vomiting of pregnancy. In addition, nausea and
      vomiting of pregnancy should be distinguished from nausea and vomiting related to
      other causes. The purpose of this document is to review the best available
      evidence about the diagnosis and management of nausea and vomiting of pregnancy. 

PMID- 26287789
TI  - Committee Opinion No. 638: First-Trimester Risk Assessment for Early-Onset
      Preeclampsia.
AB  - Hypertensive disorders with adverse sequelae (including preterm birth, maternal
      morbidity and mortality, and long-term risk of maternal cardiovascular disease)
      complicate 5-10% of pregnancies. Early identification of pregnant women at risk
      of developing early-onset preeclampsia would theoretically allow referral for
      more intensive surveillance or application of preventive therapies to reduce the
      risk of severe disease. In practice, however, the effectiveness of such triage
      would be hindered by the low positive predictive value for early-onset
      preeclampsia reported in the literature. In spite of the modest predictive value
      of first-trimester preeclampsia risk assessment and the lack of data
      demonstrating improved clinical outcomes, commercial tests are being marketed for
      the prediction of preeclampsia in the first trimester. Taking a detailed medical
      history to evaluate for risk factors is currently the best and only recommended
      screening approach for preeclampsia; it should remain the method of screening for
      preeclampsia until studies show that aspirin or other interventions reduce the
      incidence of preeclampsia for women at high risk based on first-trimester
      predictive tests. 

PMID- 26287790
TI  - Committee Opinion No. 639: The Importance of Vital Records and Statistics for the
      Obstetrician-Gynecologist.
AB  - Information from vital records is critical to identify and quantify health
      related issues and to measure progress toward quality improvement and public
      health goals. In particular, maternal and infant mortality serve as important
      indicators of the nation's health, thereby influencing policy development,
      funding of programs and research, and measures of health care quality. Accurate
      and timely documentation of births and deaths is essential to high-quality vital
      statistics. This Committee Opinion describes the process by which births,
      maternal deaths, and fetal deaths are registered; the challenges faced with a
      decentralized reporting system; and the important role for obstetrician
      gynecologists in improving the accuracy, reliability, and timeliness of vital
      records. 

PMID- 26287791
TI  - Committee Opinion No. 640: Cell-Free DNA Screening For Fetal Aneuploidy.
AB  - Noninvasive prenatal screening that uses cell-free DNA from the plasma of
      pregnant women offers tremendous potential as a screening method for fetal
      aneuploidy. A number of laboratories have validated different techniques for the
      use of cell-free DNA as a screening test for fetal aneuploidy. All tests have a
      high sensitivity and specificity for trisomy 18 and trisomy 21, regardless of
      which molecular technique is used. Women whose results are not reported,
      indeterminate, or uninterpretable (a "no call" test result) from cell-free DNA
      screening should receive further genetic counseling and be offered comprehensive
      ultrasound evaluation and diagnostic testing because of an increased risk of
      aneuploidy. Patients should be counseled that cell-free DNA screening does not
      replace the precision obtained with diagnostic tests, such as chorionic villus
      sampling or amniocentesis and, therefore, is limited in its ability to identify
      all chromosome abnormalities. Cell-free DNA screening does not assess risk of
      fetal anomalies such as neural tube defects or ventral wall defects. Patients who
      are undergoing cell-free DNA screening should be offered maternal serum alpha
      fetoprotein screening or ultrasound evaluation for risk assessment. The cell-free
      DNA screening test should not be considered in isolation from other clinical
      findings and test results. Management decisions, including termination of the
      pregnancy, should not be based on the results of the cell-free DNA screening
      alone. Patients should be counseled that a negative cell-free DNA test result
      does not ensure an unaffected pregnancy. Given the performance of conventional
      screening methods, the limitations of cell-free DNA screening performance, and
      the limited data on cost-effectiveness in the low-risk obstetric population,
      conventional screening methods remain the most appropriate choice for first-line
      screening for most women in the general obstetric population. 

PMID- 26287792
TI  - Committee Opinion No. 641: Human Papillomavirus Vaccination.
AB  - Human papillomavirus (HPV) is associated with the development of anogenital
      cancer (including cervical, vaginal, vulvar, penile, and anal), oropharyngeal
      cancer, and genital warts. Human papillomavirus vaccination can significantly
      reduce the incidence of anogenital cancer and genital warts. Despite the benefits
      of HPV vaccines, only approximately one third of girls in the recommended age
      group have received all three vaccines. Compared with other vaccines recommended
      in the same age bracket, HPV vaccination rates in the United States are
      unacceptably low. It is crucial that obstetrician-gynecologists and other
      providers educate parents and patients on the benefits and safety of HPV
      vaccination. The Centers for Disease Control and Prevention and the American
      College of Obstetricians and Gynecologists recommend routine vaccination with HPV
      vaccine for girls and boys. The 9-valent HPV vaccine is recommended by the
      Advisory Committee on Immunization Practices and was licensed by the U.S. Food
      and Drug Administration in December 2014 for girls and boys aged 11-12 years. 

PMID- 26287793
TI  - The Regional Asthma Disease Management Program (RADMP) for low income underserved
      children in rural western North Carolina: a National Asthma Control Initiative
      Demonstration Project.
AB  - BACKGROUND: A substantial proportion of low-income children with asthma living in
      rural western North Carolina have suboptimal asthma management. To address the
      needs of these underserved children, we developed and implemented the Regional
      Asthma Disease Management Program (RADMP); RADMP was selected as one of 13
      demonstration projects for the National Asthma Control Initiative (NACI).
      METHODS: This observational intervention was conducted from 2009 to 2011 in 20
      rural counties and the Eastern Band Cherokee Indian Reservation in western North
      Carolina. Community and individual intervention components included asthma
      education in-services and environmental assessments/remediation. The individual
      intervention also included clinical assessment and management. RESULTS:
      Environmental remediation was conducted in 13 childcare facilities and 50 homes;
      over 259 administrative staff received asthma education. Fifty children with mild
      to severe persistent asthma were followed for up to 2 years; 76% were enrolled in
      Medicaid. From 12-month pre-intervention to 12-month post-intervention, the total
      number of asthma-related emergency department (ED) visits decreased from 158 to 4
      and hospital admissions from 62 to 1 (p < 0.0001). From baseline to intervention
      completion, lung function FVC, FEV1, FEF 25-75 increased by 7.2%, 13.2% and
      21.1%, respectively (all p < 0.001), and average school absences dropped from 17
      to 8.8 days. Healthcare cost avoided 12 months post-intervention were
      approximately $882,021. CONCLUSION: The RADMP program resulted in decreased ED
      visits, hospitalizations, school absences and improved lung function and eNO.
      This was the first NACI demonstration project to show substantial improvements in
      healthcare utilization and clinical outcomes among rural asthmatic children.

PMID- 26287794
TI  - Ligand Binding to Chlorite Dismutase from Magnetospirillum sp.
AB  - Chlorite dismutase (Cld) catalyzes the reduction of chlorite to chloride and
      dioxygen. Here, the ligand binding to Cld of Magnetospirillum sp. (MaCld) is
      investigated with X-ray crystallography and electron paramagnetic resonance
      (EPR). EPR reveals a large heterogeneity in the structure of wild-type MaCld,
      showing a variety of low- and high-spin ferric heme forms. Addition of an axial
      ligand, such as azide or imidazole, removes this heterogeneity almost entirely.
      This is in line with the two high resolution crystal structures of MaCld obtained
      in the presence of azide and thiocyanate that show the coordination of the
      ligands to the heme iron. The crystal structure of the MaCld-azide complex
      reveals a single well-defined orientation of the azide molecule in the heme
      pocket. EPR shows, however, a pH-dependent heme structure, probably due to acid
      base transitions of the surrounding amino-acid residues stabilizing azide. For
      the azide and imidazole complex of MaCld, the hyperfine and nuclear quadrupole
      interactions with the close-by (14)N and (1)H nuclei are determined using pulsed
      EPR. These values are compared to the corresponding data for the low-spin forms
      observed in the ferric wild-type MaCld and to existing EPR data on azide and
      imidazole complexes of other heme proteins. 

PMID- 26287795
TI  - The association between orthostatic increase in pulse pressure and ischemic heart
      disease.
AB  - The clinical meaning of changes in PP with posture remains unclear. We performed
      treadmill exercise testing on 144 subjects to diagnose ischemic heart disease,
      and measured the PPs in the supine and standing positions. The differences in the
      two PPs ranged between -35 and 45 mmHg. Eleven subjects were diagnosed with
      significant coronary ischemia. The differences in the PPs were significantly
      increased, and PP in the standing position was significantly elevated in these
      subjects. A large difference in the PPs in the standing and supine positions was
      associated with significant coronary ischemia, independent of significant
      covariables. 

PMID- 26287796
TI  - Is there a relationship between low vitamin D and rotaviral diarrhea?
AB  - BACKGROUND: For children under 5 years of age, 1700 000 000 episodes of diarrhea
      are seen worldwide, and death occurs in 700 000 of these cases due to diarrhea.
      Rotavirus is an important cause of diarrhea in this age group, and many studies
      have shown that vitamin D plays a pivotal role in the immune system, as well as
      in antimicrobial peptide gene expression. In addition, lower vitamin D has been
      correlated with higher rates of infectious diseases such as respiratory tract
      infection, tuberculosis, and viral infection. METHODS: Seventy patients with
      rotaviral diarrhea and 67 healthy patients were enrolled in this study. Serum 25
      hydroxy vitamin D(3) (25(OH)D(3)), parathormone, calcium, phosphate, alkaline
      phosphatase, complete blood count parameters, and C-reactive protein were
      compared between pre-school children hospitalized due to rotaviral diarrhea and
      healthy children. Additionally, birthweight, feeding habits in the first 6 months
      of life, vitamin D and multivitamin supplements, and rotaviral vaccinations were
      also evaluated in each group. RESULTS: There were no differences between the
      groups with regard to gender and age, but 25(OH)D(3) was significantly different:
      14.6 +/- 8.7 ng/mL in the rotaviral diarrhea patients versus 29.06 +/- 6.51 ng/mL
      in the health controls (P < 0.001), and serum 25(OH)D(3) <20 ng/mL (OR, 6.3;
      95%CI: 3.638-10.909; P < 0.001) was associated with rotaviral diarrhea.
      CONCLUSIONS: Low vitamin D is associated with rotaviral diarrhea. This is the
      first study in the literature to show this, and this result needs to be repeated
      in larger controlled clinical studies.

PMID- 26287797
TI  - Acute Splenic Sequestration Crisis in Adult Sickle Cell Disease: A Report of 16
      Cases.
AB  - Acute splenic sequestration crisis (ASSC), characterized by rapidly progressive
      anemia and circulatory compromise in the setting of sudden splenic enlargement,
      is an uncommon entity among adult sickle cell patients. We reviewed cases of
      adult ASSC encountered at our institution to generate insight into the
      recognition, diagnosis, and treatment of the condition. Cases of adult ASSC
      during a 10-year period were identified retrospectively. Patient charts were
      reviewed for laboratory and imaging results; demographic data and clinical course
      were collected and reviewed. Sixteen cases of adult ASSC were identified. Most
      patients presented with pain crisis; only four of 16 patients presented with
      abdominal pain. The maximum decreases in hemoglobin (Hb) (42.0%) and platelets
      (62.1%) occurred at day 2.9, delaying identification and treatment. Hemodynamic
      instability played a large role in dictating risk stratification. Therapy
      consisted of transfusion (14/16) and splenectomy (5/16). No recurrences were
      noted in a mean follow-up time of 5.3 years but review of patients' charts
      demonstrated that at least one of the patients had two prior episodes. Adult ASSC
      may present with non specific findings and patients may not deteriorate until
      several days into a previously uneventful hospital course. Changes in platelet
      counts may be more reliable markers than changes in Hb level since red cell
      transfusions may interfere with assessments of the sequestration process. This
      case series of adult ASSC, the largest reported in the literature to date,
      highlights common clinical, laboratory, radiological, and pathological features
      of this uncommon entity and helps to guide recognition, diagnosis, and treatment.

PMID- 26287799
TI  - Encapsulation of N-Diazeniumdiolates within Liposomes for Enhanced Nitric Oxide
      Donor Stability and Delivery.
AB  - The rapid decomposition of nitric oxide (NO) donors in aqueous environments
      remains a limitation for applications requiring extended NO release. Herein, we
      report the synthesis of dipalmitoylphosphatidylcholine-based liposomes capable of
      extended NO release using low molecular weight NO donors and a reverse-phase
      evaporation technique. The encapsulation of the NO donors within the liposomes
      enabled both prolonged NO release and enhanced storage compared to free NO donors
      alone. The NO-releasing liposomes also demonstrated enhanced efficacy against
      human pancreatic cancer cells. These NO-release vehicles represent attractive
      anticancer therapeutics due to their potential to store the majority of their NO
      payload until reaching cancerous tissue at which time the lower pH inherent to
      such environments will trigger an avalanche of NO. 

PMID- 26287798
TI  - Biological and Clinical Significance of MAD2L1 and BUB1, Genes Frequently
      Appearing in Expression Signatures for Breast Cancer Prognosis.
AB  - To investigate the biologic relevance and clinical implication of genes involved
      in multiple gene expression signatures for breast cancer prognosis, we identified
      16 published gene expression signatures, and selected two genes, MAD2L1 and BUB1.
      These genes appeared in 5 signatures and were involved in cell-cycle regulation.
      We analyzed the expression of these genes in relation to tumor features and
      disease outcomes. In vitro experiments were also performed in two breast cancer
      cell lines, MDA-MB-231 and MDA-MB-468, to assess cell proliferation, migration
      and invasion after knocking down the expression of these genes. High expression
      of these genes was found to be associated with aggressive tumors and poor disease
      free survival of 203 breast cancer patients in our study, and the association
      with survival was confirmed in an online database consisting of 914 patients. In
      vitro experiments demonstrated that lowering the expression of these genes by
      siRNAs reduced tumor cell growth and inhibited cell migration and invasion. Our
      investigation suggests that MAD2L1 and BUB1 may play important roles in breast
      cancer progression, and measuring the expression of these genes may assist the
      prediction of breast cancer prognosis. 

PMID- 26287802
TI  - Use of checklists improves the quality and safety of prehospital emergency care.
AB  - OBJECTIVES: High-level emergency medical care requires transfer of evidence-based
      knowledge into practice. Our study is the first to investigate the feasibility of
      checklists in improving prehospital emergency care. MATERIALS AND METHODS: Three
      checklists based on standard operating procedures were introduced: General
      principles of prehospital care, acute coronary syndrome and acute asthma/acutely
      exacerbated chronic obstructive pulmonary disease. Subsequent to prehospital care
      and immediately before transport, information on medical history, diagnostic and
      therapeutic procedures was obtained. Data of 740 emergency missions were recorded
      prospectively before (control group) and after implementation of checklists and
      compared using the chi-test (significance level P<0.05). RESULTS: Documentation
      on patients' history (pre-existing diseases: 69.1 vs. 74.3%; medication: 55.8 vs.
      68.0%; allergies: 6.2 vs. 27.7%) and diagnostic measures (oxygen saturation: 93.2
      vs. 98.1%; auscultation: 11.1 vs. 19.9%) as well as basic treatment procedures
      (application of oxygen: 73.2 vs. 85.3%; intravenous access: 84.6 vs. 92.2%)
      increased significantly. Subanalysis of acute coronary syndrome cases showed a
      significant increase of 12-lead ECG use (74.3 vs. 92.4%), administration of
      oxygen (84.2 vs. 98.6%), ASA (71.7 vs. 81.9%), heparin (71.1 vs. 84.0%), beta
      blockers (39.5 vs. 57.1%) and morphine (26.8 vs. 44.6%). In the chronic
      obstructive pulmonary disease subgroup, oxygen supply (78.8 vs. 98.5%) and
      application of inhalative and intravenous beta2-mimetics (42.4 vs. 66.7% and 12.1
      vs. 37.9%) increased significantly. CONCLUSION: Introduction of checklists for
      prehospital emergency care may help to improve adherence to treatment guidelines.
      Additional efforts (e.g. team trainings) have to be made to increase quality of
      care.

PMID- 26287800
TI  - Developmental Expression and Glucocorticoid Control of the Leptin Receptor in
      Fetal Ovine Lung.
AB  - The effects of endogenous and synthetic glucocorticoids on fetal lung maturation
      are well-established, although the role of leptin in lung development before
      birth is unclear. This study examined mRNA and protein levels of the signalling
      long-form leptin receptor (Ob-Rb) in fetal ovine lungs towards term, and after
      experimental manipulation of glucocorticoid levels in utero by fetal cortisol
      infusion or maternal dexamethasone treatment. In fetal ovine lungs, Ob-Rb protein
      was localised to bronchiolar epithelium, bronchial cartilage, vascular
      endothelium, alveolar macrophages and type II pneumocytes. Pulmonary Ob-Rb mRNA
      abundance increased between 100 (0.69 fractional gestational age) and 144 days
      (0.99) of gestation, and by 2-4-fold in response to fetal cortisol infusion and
      maternal dexamethasone treatment. In contrast, pulmonary Ob-Rb protein levels
      decreased near term and were halved by glucocorticoid treatment, without any
      significant change in phosphorylated signal transducer and activator of
      transcription-3 (pSTAT3) at Ser727, total STAT3 or the pulmonary pSTAT3:STAT3
      ratio. Leptin mRNA was undetectable in fetal ovine lungs at the gestational ages
      studied. These findings demonstrate differential control of pulmonary Ob-Rb
      transcript abundance and protein translation, and/or post-translational
      processing, by glucocorticoids in utero. Localisation of Ob-Rb in the fetal ovine
      lungs, including alveolar type II pneumocytes, suggests a role for leptin
      signalling in the control of lung growth and maturation before birth. 

PMID- 26287804
TI  - Which adverse events should be reported in an emergency department? A Delphi
      study.
AB  - OBJECTIVE: The aim of this study was to determine if emergency medicine specific
      triggers for completing an incident form could be agreed and if a common
      definition for contributory factors could be achieved. Such definitions could be
      used to improve safety within the emergency department (ED) and share learning
      across the specialty. PARTICIPANTS AND METHODS: One hundred and fifteen ED safety
      leads in the UK and Ireland were invited to participate in a Delphi study. This
      process took 1 year to complete. In the first round, participants listed 20
      events that should be reported as an adverse event and 20 contributory factors
      that could contribute to risk or harm. An 80% concordance level was sought for
      both aspects. RESULTS: Eighty-four per cent of safety leads participated in the
      first round, although this decreased over subsequent rounds to 43%. Four hundred
      and eighty-five triggers were initially suggested; eventually, 27 triggers that
      should always or usually be reported achieved 80% concordance. Sixty-eight
      contributory factors were initially identified with eventual agreement being
      reached on 27 remediable contributory factors. CONCLUSION: The process
      demonstrated agreement amongst emergency physicians in the UK and Ireland on the
      type of events that should be formally reported. The lists emerging from this
      process should not be viewed as exhaustive; rather they should be used to
      encourage the reporting of incidents and designing safer systems and processes
      within the ED.

PMID- 26287803
TI  - ECG interpretation in Emergency Department residents: an update and e-learning as
      a resource to improve skills.
AB  - OBJECTIVE: ECG interpretation is a pivotal skill to acquire during residency,
      especially for Emergency Department (ED) residents. Previous studies reported
      that ECG interpretation competency among residents was rather low. However, the
      optimal resource to improve ECG interpretation skills remains unclear. The aim of
      our study was to compare two teaching modalities to improve the ECG
      interpretation skills of ED residents: e-learning and lecture-based courses.
      PARTICIPANTS AND METHODS: The participants were first-year and second-year ED
      residents, assigned randomly to the two groups. The ED residents were evaluated
      by means of a precourse test at the beginning of the study and a postcourse test
      after the e-learning and lecture-based courses. These evaluations consisted of
      the interpretation of 10 different ECGs. RESULTS: We included 39 ED residents
      from four different hospitals. The precourse test showed that the overall average
      score of ECG interpretation was 40%. Nineteen participants were then assigned to
      the e-learning course and 20 to the lecture-based course. Globally, there was a
      significant improvement in ECG interpretation skills (accuracy score=55%,
      P=0.0002). However, this difference was not significant between the two groups
      (P=0.14). CONCLUSION: Our findings showed that the ECG interpretation was not
      optimal and that our e-learning program may be an effective tool for enhancing
      ECG interpretation skills among ED residents. A large European study should be
      carried out to evaluate ECG interpretation skills among ED residents before the
      implementation of ECG learning, including e-learning strategies, during ED
      residency.

PMID- 26287805
TI  - Frequent users of the emergency department services in the largest academic
      hospital in the Netherlands: a 5-year report.
AB  - OBJECTIVE: To investigate the demographic and service characteristics, motive for
      consultation, and disposition of adult frequent users (FUs) of the largest
      academic hospital in the Netherlands over a 5-year period. PATIENTS AND METHODS:
      This retrospective study included all patients aged 18 years and older visiting
      the emergency department (ED) during a 5-year period (2009-2013). Frequent ED use
      was defined as having four or more visits to the ED during a year. Patient and
      service characteristics, motive for consultation, and disposition were explored.
      RESULTS: Frequent ED users represented 2% of all patients who visited the ED
      during 2009-2013 (8% of all ED consultations). On average, each FU visited the ED
      five times per year. Compared with nonfrequent users (NFUs), FUs were
      significantly less often self-referred, less frequently transported to the
      hospital by ambulance, received a lower urgency code upon arrival to the ED, and
      more often admitted to hospital than NFUs. Complaints related to the digestive
      system (19%), general complaints such as fever (18%), respiratory (10%), or
      cardiovascular problems (10%) were the main motive for consultations of the
      frequent ED users. Two percent of the FUs were serial FUs (FUs during 3 or more
      consecutive years). CONCLUSION: Frequent use of the ED has been depicted as
      inappropriate use of these services. However, our study shows that FUs consist of
      a relatively small number of patients and that FUs suffer from chronic, and
      often, severe somatic illnesses that require specialized medical care.

PMID- 26287806
TI  - Prospective evaluation of the Eppendorf-Cologne Scale.
AB  - OBJECTIVES: Early diagnosis of traumatic brain injury and reliable prediction of
      outcome are essential for determining treatment strategies and allocating
      resources. This study re-evaluates the Eppendorf-Cologne Scale (ECS) and its
      predictive accuracy for outcome compared with the Glasgow Coma Scale (GCS).
      METHODS: A prospective cohort analysis of severely injured trauma patients
      registered in the Trauma Registry of the German Society for Trauma Surgery from
      2012-2013 was carried out. Only directly admitted patients alive on admission
      with complete data on GCS, ECS and outcome in terms of survival to hospital
      discharge or death were included. The predictive accuracy in terms of the outcome
      of the ECS and the GCS was modelled using area under the receiver operating
      characteristic (AUROC) curve analysis. RESULTS: A total of 17 616 patients
      fulfilled the study inclusion criteria. The ECS outmatched the predictive
      accuracy of the GCS for outcome (AUROC, 0.853, 95% confidence interval, 0.831
      0.854; and AUROC 0.836; 95% confidence interval, 0.825-0.848, respectively;
      P=0.062). An ECS score of 8 was associated with a 25-fold higher mortality
      compared with an ECS score of 0. Patients who had an ECS score of 8 had a 1.5
      fold higher mortality compared with patients allocated a GCS score of 3.
      CONCLUSION: The ECS shows a higher accuracy for prediction of outcome compared
      with the GCS and enables further differentiation within the critical GCS 3
      collective.

PMID- 26287807
TI  - Implications of Cardiovascular Disease Risk Assessment Using the WHO/ISH Risk
      Prediction Charts in Rural India.
AB  - Cardiovascular disease (CVD) risk in India is currently assessed using the World
      Health Organization/International Society for Hypertension (WHO/ISH) risk
      prediction charts since no population-specific models exist. The WHO/ISH risk
      prediction charts have two versions-one with total cholesterol as a predictor
      (the high information (HI) model) and the other without (the low information (LI)
      model). However, information on the WHO/ISH risk prediction charts including
      guidance on which version to use and when, as well as relative performance of the
      LI and HI models, is limited. This article aims to, firstly, quantify the
      relative performance of the LI and HI WHO/ISH risk prediction (for WHO-South East
      Asian Region D) using data from rural India. Secondly, we propose a pre-screening
      (simplified) point-of-care (POC) test to identify patients who are likely to
      benefit from a total cholesterol (TC) test, and subsequently when the LI model is
      preferential to HI model. Analysis was performed using cross-sectional data from
      rural Andhra Pradesh collected in 2005 with recorded blood cholesterol
      measurements (N = 1066). CVD risk was computed using both LI and HI models, and
      high risk individuals who needed treatment(THR) were subsequently identified
      based on clinical guidelines. Model development for the POC assessment of a TC
      test was performed through three machine learning techniques: Support Vector
      Machine (SVM), Regularised Logistic Regression (RLR), and Random Forests (RF)
      along with a feature selection process. Disagreement in CVD risk predicted by LI
      and HI WHO/ISH models was 14.5% (n = 155; p<0.01) overall and comprised 36
      clinically relevant THR patients (31% of patients identified as THR by using
      either model). Using two patient-specific parameters (age, systolic blood
      pressure), our POC assessment can pre-determine the benefit of TC testing and
      choose the appropriate risk model (out-of-sample AUCs:RF-0.85,SVM-0.84,RLR:0.82
      and maximum sensitivity-98%). The identification of patients benefitting from a
      TC test for CVD risk stratification can aid planning for resource-allocation and
      save costs for large-scale screening programmes. 

PMID- 26287808
TI  - Hydrophobically Modified Keratin Vesicles for GSH-Responsive Intracellular Drug
      Release.
AB  - Redox-responsive polymersomes were prepared by self-assembly of a hydrophobically
      modified keratin and employing a water addition/solvent evaporation method.
      Polyethylene glycol-40 stearate (PEG40ST) was chosen as hydrophobic block to be
      coupled to keratin via radical grafting. The amphiphilic polymer exhibited low
      critical aggregation concentration (CAC; 10 MUg/mL), indicating a good
      thermodynamic stability. The polymeric vesicles loaded both hydrophilic
      methotrexate and hydrophobic curcumin with high entrapment efficiencies, and
      showed a GSH-dependent drug release rate. Confocal studies on HeLa cells revealed
      that the obtained polymersomes were efficiently internalized. Biocompatibility
      properties of the proposed delivery vehicle were assessed in HET-CAM test and
      Balb-3T3 mouse fibroblasts. Polymersomes loaded with either methotrexate or
      curcumin inhibited HeLa and CHO-K1 cancer cells proliferation. Overall, the
      proposed keratin polymersomes could be efficient nanocarriers for
      chemotherapeutic agents. 

PMID- 26287810
TI  - Identification of Race and Ethnicity in Large Databases.

PMID- 26287811
TI  - High-Concentration Synthesis of Sub-10-nm Copper Nanoparticles for Application to
      Conductive Nanoinks.
AB  - A simple, high-concentration (up to 0.6 M Cu salt) synthesis of sub-10-nm copper
      nanoparticles (Cu NPs) was developed in ethylene glycol at room temperature under
      ambient air conditions using 1-amino-2-propanol (AmIP) as the stabilizer.
      Monodispersed AmIP-Cu NPs of 3.5 +/- 1.0 nm were synthesized in a high yield of
      ~90%. Thus, nearly 1 g of sub-10-nm Cu NP powder was obtained using a one-step
      synthesis for the first time. It is proposed that metallacyclic coordination
      stability of a five-membered ring type between the Cu and AmIP causes the high
      binding force of Am IP onto the Cu surface, resulting in the superior stability
      of the AmIP-Cu NPs in a solution. The purified powder of AmIP-Cu NPs can be
      redispersed in alcohol-based solvents up to high Cu contents of 45 wt % for the
      preparation of Cu nanoink. The resistivity of the conductive Cu film obtained
      from the Cu nanoink was 30 MUOmega cm after thermal heating at 150  degrees C for
      15 min under a nitrogen flow. The long-term resistance stability of the Cu film
      under an air atmosphere was also demonstrated. 

PMID- 26287809
TI  - Second tectofugal pathway in a songbird (Taeniopygia guttata) revisited: Tectal
      and lateral pontine projections to the posterior thalamus, thence to the
      intermediate nidopallium.
AB  - Birds are almost always said to have two visual pathways from the retina to the
      telencephalon: thalamofugal terminating in the Wulst, and tectofugal terminating
      in the entopallium. Often ignored is a second tectofugal pathway that terminates
      in the nidopallium medial to and separate from the entopallium (e.g., Gamlin and
      Cohen [1986] J Comp Neurol 250:296-310). Using standard tract-tracing and
      electroanatomical techniques, we extend earlier evidence of a second tectofugal
      pathway in songbirds (Wild [1994] J Comp Neurol 349:512-535), by showing that
      visual projections to nucleus uvaeformis (Uva) of the posterior thalamus in zebra
      finches extend farther rostrally than to Uva, as generally recognized in the
      context of the song control system. Projections to "rUva" resulted from
      injections of biotinylated dextran amine into the lateral pontine nucleus (PL),
      and led to extensive retrograde labeling of tectal neurons, predominantly in
      layer 13. Injections in rUva also resulted in extensive retrograde labeling of
      predominantly layer 13 tectal neurons, retrograde labeling of PL neurons, and
      anterograde labeling of PL. It thus appears that some tectal neurons could
      project to rUva and PL via branched axons. Ascending projections of rUva
      terminated throughout a visually responsive region of the intermediate
      nidopallium (NI) lying between the nucleus interface medially and the entopallium
      laterally. Lastly, as shown by Clarke in pigeons ([1977] J Comp Neurol 174:535
      552), we found that PL projects to caudal cerebellar folia.

PMID- 26287813
TI  - Handheld-automated microsurgical instrumentation for intraocular laser surgery.
AB  - BACKGROUND AND OBJECTIVE: Laser photocoagulation is a mainstay or adjuvant
      treatment for a variety of common retinal diseases. Automated laser
      photocoagulation during intraocular surgery has not yet been established. The
      authors introduce an automated laser photocoagulation system for intraocular
      surgery, based on a novel handheld instrument. The goals of the system are to
      enhance accuracy and efficiency and improve safety. MATERIALS AND METHODS: Triple
      ring patterns are introduced as a typical arrangement for the treatment of
      proliferative retinopathy and registered to a preoperative fundus image. In
      total, 32 target locations are specified along the circumferences of three rings
      having diameters of 1, 2, and 3 mm, with a burn spacing of 600 MUm. Given the
      initial system calibration, the retinal surface is reconstructed using stereo
      vision, and the targets specified on the preoperative image are registered with
      the control system. During automated operation, the laser probe attached to the
      manipulator of the active handheld instrument is deflected as needed via visual
      servoing in order to correct the error between the aiming beam and a specified
      target, regardless of any erroneous handle motion by the surgeon. A constant
      distance of the laser probe from the retinal surface is maintained in order to
      yield consistent size of burns and ensure safety during operation. Real-time
      tracking of anatomical features enables compensation for any movement of the eye.
      A graphical overlay system within operating microscope provides the surgeon with
      guidance cues for automated operation. Two retinal surgeons performed automated
      and manual trials in an artificial model of the eye, with each trial repeated
      three times. For the automated trials, various targeting thresholds (50-200 MUm)
      were used to automatically trigger laser firing. In manual operation, fixed
      repetition rates were used, with frequencies of 1.0-2.5 Hz. The power of the 532
      nm laser was set at 3.0 W with a duration of 20 ms. After completion of each
      trial, the speed of operation and placement error of burns were measured. The
      performance of the automated laser photocoagulation was compared with manual
      operation, using interpolated data for equivalent firing rates from 1.0 to 1.75
      Hz. RESULTS: In automated trials, average error increased from 45 +/- 27 to 60 +/
      37 MUm as the targeting threshold varied from 50 to 200 MUm, while average
      firing rate significantly increased from 0.69 to 1.71 Hz. The average error in
      the manual trials increased from 102 +/- 67 to 174 +/- 98 MUm as firing rate
      increased from 1.0 to 2.5 Hz. Compared to the manual trials, the average error in
      the automated trials was reduced by 53.0-56.4%, resulting in statistically
      significant differences (P <= 10(-20) ) for all equivalent frequencies (1.0-1.75
      Hz). The depth of the laser tip in the automated trials was consistently
      maintained within 18 +/- 2 MUm root-mean-square (RMS) of its initial position,
      whereas it significantly varied in the manual trials, yielding an error of 296 +/
      30 MUm RMS. At high firing rates in manual trials, such as at 2.5 Hz, laser
      photocoagulation is marginally attained, yielding failed burns of 30% over the
      entire pattern, whereas no failed burns are found in automated trials. Relatively
      regular burn sizes are attained in the automated trials by the depth servoing of
      the laser tip, while burn sizes in the manual trials vary considerably. Automated
      avoidance of blood vessels was also successfully demonstrated, utilizing the
      retina-tracking feature to identify avoidance zones. CONCLUSION: Automated
      intraocular laser surgery can improve the accuracy of photocoagulation while
      ensuring safety during operation. This paper provides an initial demonstration of
      the technique under reasonably realistic laboratory conditions; development of a
      clinically applicable system requires further work.

PMID- 26287815
TI  - Synthesis of g-C3N4/CaIn2S4 composites with enhanced photocatalytic activity
      under visible light irradiation.
AB  - A series of graphite-like g-C3N4 hybridized CaIn2S4 photocatalysts with different
      g-C3N4 contents were fabricated via a facile hydrothermal synthetic method. These
      as-prepared samples were characterized by X-ray diffraction (XRD), scanning
      electron microscopy (SEM), transmission electron microscopy (TEM), UV-Visible
      absorption spectra (UV-Vis) and Fourier transform infrared (FT-IR) spectra. Under
      visible light irradiation, the as-prepared g-C3N4/CaIn2S4 nanocomposites showed
      enhanced photocatalytic performance for rhodamine B (RhB) degradation. The sample
      with 5 wt% g-C3N4 hybridized CaIn2S4 exhibited the highest photocatalytic
      activity. The enhanced photocatalytic performance under visible light irradiation
      could be attributed to the high separation efficiency of the photogenerated
      electron-hole pairs. This work could provide a new insight into the fabrication
      of visible light driven photocatalysts with efficient and stable performance. 

PMID- 26287812
TI  - Get real in individual participant data (IPD) meta-analysis: a review of the
      methodology.
AB  - Individual participant data (IPD) meta-analysis is an increasingly used approach
      for synthesizing and investigating treatment effect estimates. Over the past few
      years, numerous methods for conducting an IPD meta-analysis (IPD-MA) have been
      proposed, often making different assumptions and modeling choices while
      addressing a similar research question. We conducted a literature review to
      provide an overview of methods for performing an IPD-MA using evidence from
      clinical trials or non-randomized studies when investigating treatment efficacy.
      With this review, we aim to assist researchers in choosing the appropriate
      methods and provide recommendations on their implementation when planning and
      conducting an IPD-MA.

PMID- 26287816
TI  - Microwave-Assisted Synthesis of Boron and Nitrogen co-doped Reduced Graphene
      Oxide for the Protection of Electromagnetic Radiation in Ku-Band.
AB  - The electromagnetic interference (EMI) shielding of reduced graphene oxide (MRG),
      B-doped MRG (B-MRG), N-doped MRG (N-MRG), and B-N co-doped MRG (B-N-MRG) have
      been studied in the Ku-band frequency range (12.8-18 GHz). We have developed a
      green, fast, and cost-effective microwave assisted route for synthesis of doped
      MRG. B-N-MRG shows high electrical conductivity in comparison to MRG, B-MRG and N
      MRG, which results better electromagnetic interference (EMI) shielding ability.
      The co-doping of B and N significantly enhances the electrical conductivity of
      MRG from 21.4 to 124.4 Sm(-1) because N introduces electrons and B provides holes
      in the system and may form a nanojunction inside the material. Their temperature
      dependent electrical conductivity follows 2D-variable range hopping (2D-VRH) and
      Efros-Shklovskii-VRH (ES-VRH) conduction model in a low temperature range (T<50
      K). The spatial configuration of MRG after doping of B and N enhances the space
      charge polarization, natural resonance, dielectric polarization, and trapping of
      EM waves by internal reflection leading to a high EMI shielding of -42 dB
      (~99.99% attenuation) compared to undoped MRG (-28 dB) at a critical thickness of
      1.2 mm. Results suggest that the B-N-MRG has great potential as a candidate for a
      new type of EMI shielding material useful in aircraft, defense industries,
      communication systems, and stealth technology.

PMID- 26287814
TI  - The Number and Complexity of Pure and Recombinant HIV-1 Strains Observed within
      Incident Infections during the HIV and Malaria Cohort Study Conducted in Kericho,
      Kenya, from 2003 to 2006.
AB  - Characterization of HIV-1 subtype diversity in regions where vaccine trials are
      conducted is critical for vaccine development and testing. This study describes
      the molecular epidemiology of HIV-1 within a tea-plantation community cohort in
      Kericho, Kenya. Sixty-three incident infections were ascertained in the HIV and
      Malaria Cohort Study conducted in Kericho from 2003 to 2006. HIV-1 strains from
      58 of those individuals were full genome characterized and compared to two
      previous Kenyan studies describing 41 prevalent infections from a blood bank
      survey (1999-2000) and 21 infections from a higher-risk cohort containing a mix
      of incident and prevalent infections (2006). Among the 58 strains from the
      community cohort, 43.1% were pure subtypes (36.2% A1, 5.2% C, and 1.7% G) and
      56.9% were inter-subtype recombinants (29.3% A1D, 8.6% A1CD, 6.9% A1A2D, 5.2%
      A1C, 3.4% A1A2CD, and 3.4% A2D). This diversity and the resulting genetic
      distance between the observed strains will need to be addressed when vaccine
      immunogens are chosen. In consideration of current vaccine development efforts,
      the strains from these three studies were compared to five candidate vaccines
      (each of which are viral vectored, carrying inserts corresponding to parts of
      gag, pol, and envelope), which have been developed for possible use in sub
      Saharan Africa. The sequence comparison between the observed strains and the
      candidate vaccines indicates that in the presence of diverse recombinants, a
      bivalent vaccine is more likely to provide T-cell epitope coverage than
      monovalent vaccines even when the inserts of the bivalent vaccine are not subtype
      matched to the local epidemic. 

PMID- 26287817
TI  - Leptospermum flavescens Constituent-LF1 Causes Cell Death through the Induction
      of Cell Cycle Arrest and Apoptosis in Human Lung Carcinoma Cells.
AB  - Leptospermum flavescens Sm. (Myrtaceae), locally known as 'Senna makki' is a
      smallish tree that is widespread and recorded to naturally occur in the montane
      regions above 900 m a.s.l from Burma to Australia. Although the species is
      recorded to be used traditionally to treat various ailments, there is limited
      data on biological and chemical investigations of L. flavescens. The aim of the
      present study was to investigate and understand the ability of L. flavescens in
      inducing cell death in lung cancer cells. The cytotoxic potentials of the
      extraction yields (methanol, hexane, ethyl acetate and water extracts as wells as
      a semi pure fraction, LF1) were evaluated against two human non-small cell lung
      carcinoma cell lines (A549 and NCI-H1299) using the MTT assay. LF1 showed the
      greatest cytotoxic effect against both cell lines with IC50 values of 7.12 +/-
      0.07 and 9.62 +/- 0.50 MUg/ml respectively. LF1 treated cells showed a sub-G1
      region in the cell cycle analysis and also caused the presence of apoptotic
      morphologies in cells stained with acridine orange and ethidium bromide.
      Treatment with LF1 manifested an apoptotic population in cells that were
      evaluated using the Annexin V/ propidium iodide assay. Increasing dosage of LF1
      caused a rise in the presence of activated caspase-3 enzymes in treated cells.
      Blockage of cell cycle progression was also observed in LF1-treated cells. These
      findings suggest that LF1 induces apoptosis and cell cycle arrest in treated lung
      cancer cells. Further studies are being conducted to isolate and identify the
      active compound as well to better understand the mechanism involved in inducing
      cell death. 

PMID- 26287818
TI  - The Energetics of Streptococcal Enolase Octamer Formation: The Quantitative
      Contributions of the Last Eight Amino Acids at the Carboxy-Terminus.
AB  - The enolase produced by Streptococcus pyogenes is a homo-octamer whose overall
      shape resembles that of a donut. The octamer is best described as a tetramer of
      dimers. As such, it contains two types of interfaces. The first is common to
      almost all enolases as most enolases that have been studied are dimers. The
      second is unique to the octamers and includes residues near the carboxy-terminus.
      The primary sequence of the enolase contains 435 residues with an added 19 as an
      N-terminal hexahistine tag. We have systematically truncated the carboxy
      terminus, individually removing the first 8 residues. This gave rise to a series
      of eight structures containing respectively, 435, 434, 433, 432, 431, 430, 429
      and 427 residues. The truncations cause the protein to gradually dissociate from
      octamers to enzymatically inactive monomers with very small amounts of
      intermediate tetramers and dimers. We have evaluated the contributions of the
      missing residues to the monomer/octamer equilibrium using a combination of
      analytical ultracentrifugation and activity assays. For the dissociation
      reaction, octamer <== ==> 8 monomer truncation of all eight C-terminal residues
      resulted in a diminution in the standard Gibbs energy of dissociation of about 59
      kJ/mole of octamer relative to the full length protein. Considering that this
      change is spread over eight subunits, this translates to a change in standard
      Gibbs interaction energy of less than 8 kJ/mole of monomer distributed over the
      eight monomers. The resulting proteins, containing 434, 433, 432, 431, 430, 429
      and 427 residues per monomer, showed intermediate free energies of dissociation.
      Finally, three other mutations were introduced into our reference protein to
      establish how they influenced the equilibrium. The main importance of this work
      is it shows that for homo-multimeric proteins a small change in the standard
      Gibbs interaction energy between subunits can have major physiological effects.

PMID- 26287819
TI  - Modifiable Lifestyle Behaviors Are Associated With Metabolic Syndrome in a
      Taiwanese Population.
AB  - PURPOSE: To explore associations between metabolic syndrome and modifiable
      lifestyle behaviors among the adult population in Taiwan. DESIGN: This cross
      sectional study analyzed data from a nationally representative sample that
      participated in the 2005-2008 Nutrition and Health Survey in Taiwan. The sample
      (2,337 participants older than 19 years) provided data on demographic
      characteristics, modifiable lifestyle behaviors, anthropometric measurements, and
      blood chemistry panel. METHODS: These data were analyzed by descriptive
      statistics, univariate logistic regression, and multivariate logistic regression
      to determine factors associated with metabolic syndrome. FINDINGS: Metabolic
      syndrome had a prevalence of 25.2%, and this prevalence increased with age. In
      univariate regression analysis, metabolic syndrome was associated with age,
      living with family members, educational level, and modifiable lifestyle behaviors
      (smoking, drinking, betel quid chewing, and physical activity). Individuals with
      a smoking history and currently chewing betel quid had the highest risk for
      metabolic syndrome. CONCLUSIONS: The risk for metabolic syndrome might be reduced
      by public health campaigns to encourage people to quit smoking cigarettes and
      chewing betel quid. Implementing more modifiable lifestyle behaviors in daily
      life will decrease metabolic syndrome in Taiwan. CLINICAL RELEVANCE: Considering
      that betel quid chewing and tobacco smoking interact to adversely affect
      metabolic syndrome risk, public health campaigns against both behaviors seem to
      be a cost-effective and efficient health promotion strategy to reduce the
      prevalence rate of metabolic syndrome.

PMID- 26287820
TI  - Reduced Efficiency of Chlorine Disinfection of Naegleria fowleri in a Drinking
      Water Distribution Biofilm.
AB  - Naegleria fowleri associated with biofilm and biological demand water (organic
      matter suspended in water that consumes disinfectants) sourced from operational
      drinking water distribution systems (DWDSs) had significantly increased
      resistance to chlorine disinfection. N. fowleri survived intermittent chlorine
      dosing of 0.6 mg/L for 7 days in a mixed biofilm from field and laboratory
      cultured Escherichia coli strains. However, N. fowleri associated with an
      attached drinking water distribution biofilm survived more than 30 times (20 mg/L
      for 3 h) the recommended concentration of chlorine for drinking water. N. fowleri
      showed considerably more resistance to chlorine when associated with a real field
      biofilm compared to the mixed laboratory biofilm. This increased resistance is
      likely due to not only the consumption of disinfectants by the biofilm and the
      reduced disinfectant penetration into the biofilm but also the composition and
      microbial community of the biofilm itself. The increased diversity of the field
      biofilm community likely increased N. fowleri's resistance to chlorine
      disinfection compared to that of the laboratory-cultured biofilm. Previous
      research has been conducted in only laboratory scale models of DWDSs and
      laboratory-cultured biofilms. To the best of our knowledge, this is the first
      study demonstrating how N. fowleri can persist in a field drinking water
      distribution biofilm despite chlorination.

PMID- 26287821
TI  - HDlive imaging of cystic uterine leiomyoma degeneration.

PMID- 26287822
TI  - Children with congenital colorectal malformations often require special education
      or remedial teaching, despite normal intelligence.
AB  - AIM: This study prospectively evaluated neuropsychological functioning in 8-year
      old patients with anorectal malformation (ARM) and Hirschsprung's disease (HD).
      METHODS: School functioning and behaviour were assessed in a standardised
      interview. Intelligence, attention, self-esteem and quality of life were
      evaluated with validated tests and questionnaires. The following predictors were
      assessed: socio-economic status, number of episodes of general anaesthesia,
      laxative treatment and premature birth. Severely intellectually disabled patients
      were excluded. RESULTS: In total, twelve of the 23 (52%) patients with ARM and 11
      (55%) of the 20 patients with HD received special education or remedial teaching.
      The intelligence quotient was normal: mean (standard deviation or SD) was 98 (17)
      and 96 (17), respectively. However, sustained attention was below the norm: mean
      (SD) Z-score was -1.90 (1.94) and -1.43 (1.98) for ARM and HD patients; both p <
      0.01. Self-esteem was normal: mean (SD) Z-score was 0.10 (1.29) and -0.20 (1.11)
      for ARM and HD patients. Quality of life was normal in ARM patients and slightly
      impaired in HD patients. No predictors for neuropsychological outcome were
      identified. CONCLUSION: Despite normal intelligence, more than half of these
      patients received special education or remedial teaching. In addition, problems
      with sustained attention were found. These findings are important for long-term
      care.

PMID- 26287824
TI  - Responsible innovation in port development: the Rotterdam Maasvlakte 2 and the
      Dalian Dayao Bay extension projects.
AB  - The paper outlines and specifies 'responsible port innovation', introducing the
      development of a methodological and procedural step-by-step plan for the
      implementation and evaluation of (responsible) innovations. Subsequently, it uses
      this as a guideline for the analysis and evaluation of two case-studies. The
      construction of the Rotterdam Maasvlakte 2 Port meets most of the formulated
      requirements, though making values more explicit and treating it as a process
      right from the start could have benefitted the project. The Dalian Dayao Port
      could improve its decision-making procedures in several respects, including the
      introduction of new methods to handle value tensions. Both projects show that
      public support is crucial in responsible port innovation and that it should be
      not only a multi-faceted but also a multi-level strategy. 

PMID- 26287823
TI  - Possible Association of APOE Genotype with Working Memory in Young Adults.
AB  - BACKGROUND: Possession of the epsilon4 allele of the Apolipoprotein E (APOE) gene
      is associated with an increased risk of Alzheimer's disease. Early adult life
      effects of epsilon4 are less well understood. Working memory has been relatively
      little studied (compared to episodic memory) in relation to APOE genotype despite
      its importance in cognitive functioning. Our hypothesis was that epsilon4 would
      lead to an impairment in working memory in young adults. METHODS: We studied
      working memory using a computerised n-back task in the Avon Longitudinal Study of
      Parents and Children (ALSPAC) at age 18. Data was available for 1049-1927
      participants and for the 2- and 3-back versions of the task. Using multiple and
      multi-level regression controlling for important confounders we examined the
      association between APOE genotype on accuracy and reaction times. RESULTS: There
      was no evidence of a genotype effect on accuracy when the two difficulty levels
      were examined separately. There was some evidence to support a deleterious effect
      of the epsilon4 allele on n-back accuracy in the multi-level regression. There
      was weak evidence that the epsilon22 group were less accurate but the numbers
      were very low in this group. The epsilon34 group had faster reaction times than
      the reference epsilon33 group in all adjusted analyses but the epsilon44 group
      were only faster in the 3-back condition in multi-level analyses. CONCLUSIONS:
      There was no evidence of benefit in epsilon4 carriers, but there was some
      evidence of a detrimental effect on working memory in this large study.

PMID- 26287825
TI  - A review: factors affecting excess sludge anaerobic digestion for volatile fatty
      acids production.
AB  - This paper presents a review of methods that improve the production of volatile
      fatty acids (VFA) from excess sludge during the anaerobic digestion process.
      These methods are mainly divided into two approaches. The first approach is
      located in the pre-treatment methods, which change the properties of the
      substrates, such as thermal pre-treatment, alkaline pre-treatment, microwave pre
      treatment and ultrasonic pre-treatment. The other approach is found in the
      fermentation process control methods, which influence the environment of
      anaerobic digestion for the production of VFA, such as pH, temperature, mixing,
      additives and solids retention time control. In the text recent research studies
      of each method are listed and analyzed in detail. Comparably, microwave and
      ultrasonic pre-treatment methods are considered emerging and promising
      technologies due to their efficiency and environmentally friendly
      characteristics. However, the microwave pre-treatment has high electricity
      demand, which might make the process economically unfeasible. In order to
      calculate optimal operation, further studies still need to be done. 

PMID- 26287826
TI  - Effects of poly aluminum chloride dosing positions on the performance of a pilot
      scale anoxic/oxic-membrane bioreactor (A/O-MBR).
AB  - The effects of poly aluminum chloride (PACl) dosing positions on the performance
      of a pilot scale anoxic/oxic membrane bioreactor were investigated. PACl dosage
      was optimized at 19.5 mg Al2O3/L by jar test. Nutrients removal efficiencies and
      sludge properties were systematically investigated during periods with no PACl
      dosing (phase I), with PACl dosing in oxic tank (phase II) and then in anoxic
      tank (phase III). The results showed that total phosphorus removal efficiency
      increased from 18 to 88% in phase II and 85% in phase III with less than 0.5 mg
      P/L in effluent. Ammonia nitrogen removal efficiencies reached 99% in all phases
      and chemical oxygen demand removal efficiencies reached 92%, 91% and 90% in the
      three phases, respectively. Total nitrogen removal efficiency decreased from 59%
      in phase I to 49% in phases II and III. Dosing PACl in the oxic tank resulted in
      smaller sludge particle size, higher zeta potential, better sludge settleability
      and lower membrane fouling rate in comparison with dosing PACl in the anoxic
      tank. 

PMID- 26287827
TI  - Catalytic ozonation of bisphenol A in aqueous solution using Mn-Ce/HZSM-5 as
      catalyst.
AB  - Mixed manganese and cerium oxide supported on HZSM-5 were synthesized and used as
      heterogeneous catalysts for ozonation of bisphenol A (BPA) in aqueous solution.
      The prepared catalysts of Mn-Ce/HZSM-5 were characterized by X-ray diffraction,
      scanning electron microscopy and Fourier transform-infrared spectroscopy. The
      results indicated that Mn-Ce/HZSM-5 exhibits extraordinary catalytic activity for
      the degradation of BPA. Removal of 89.3% of BPA and 90.4% of total organic carbon
      (TOC) was achieved in 30 min, compared to non-catalytic ozonation, where only
      50.5% BPA and 28.1% TOC removal were reached under the same conditions.
      Adsorption of BPA on HZSM-5 support and Mn-Ce/HZSM-5 catalysts was negligible.
      The strong inhibition of BPA removal by tert-butyl alcohol indicated that the
      attack of hydroxyl radicals was responsible for the improvement of catalytic
      ozonation. It was observed that at neutral pH, which is near the point of zero
      charge of the catalyst, the catalytic activity reached its maximum. Increasing
      the amount of Mn-Ce/HZSM-5 catalyst until it exceeded 3 g/L did not show a strong
      effect on BPA removal. The catalysts showed high stability and reusability. 

PMID- 26287828
TI  - Floating wetland islands as a method of nitrogen mass reduction: results of a 1
      year test.
AB  - Floating wetland islands (FWIs) were tested in Pasco County, Florida, as a method
      of reducing total nitrogen (TN) in reclaimed water during reservoir storage. The
      Pasco County Master Reuse System (PCMRS) is a regional reclaimed-water
      transmission and distribution system providing wastewater effluent disposal for
      the county. Total daily mass loading from reclaimed water is limited by nitrogen
      content in the PCMRS watershed. To test TN reduction efficacy, 20 FWIs were
      constructed, installed, and monitored in a lined pond receiving PCMRS reclaimed
      water. In total, 149 m2 of FWIs were installed, distributed as a connected
      network covering 1,122 m2, or 7% of pond area. Pond hydraulic residence time
      averaged 15.7 days. Treatment performance was assessed during three consecutive
      periods: establishment (first 6 months of grow-in), performance (8 months
      immediately following grow-in), and control (3 months after the FWIs were removed
      from the pond). The FWIs enhanced pond nitrogen removal capacity by 32%. The
      primary effect of the FWIs was to decrease organic nitrogen in the pond outflow.
      By evaluating the difference between the performance and control periods, an
      incremental TN removal rate for the FWIs was calculated to be 4.2 kg N/m2 FWI per
      year.

PMID- 26287829
TI  - Comparative study of isotherm parameters of lead biosorption by two wastes of
      olive-oil production.
AB  - Batch isotherm studies were carried out on a laboratory scale: (i) to investigate
      the effectiveness to remove lead of two wastes (olive stone (OS) and olive tree
      pruning (OTP)), untreated and chemically treated; and (ii) to examine the
      applicability of various adsorption isotherms to fit the experimental data.
      Results from tests were analyzed using seven equilibrium isotherm correlations
      (Langmuir, Freundlich, Dubinin-Radushkevich, Temkin, Redlich-Peterson, Sips, and
      Toth equations). The sum of the squares of the errors was determined for each
      isotherm and the Langmuir equation provided the best fit. Chemical treatments
      increased the biosorption properties of these materials. The maximum biosorption
      capacities were: 6.33, 49.13, 14.83, and 38.93 mg g(-1) for untreated OS, HNO3
      OS, H2SO4-OS, and NaOH-OS, respectively, and 26.72, 86.40, 72.78, and 123.80 mg
      g(-1) for untreated OTP, HNO3-OTP, H2SO4-OTP, and NaOH-OTP, respectively.
      Finally, the loss of mass for each waste (13.9, 14.3, and 36.8% for HNO3-OS,
      H2SO4-OS, and NaOH-OS and 35.1, 27.5, and 46.7% for HNO3-OTP, H2SO4-OTP, and NaOH
      OTP, respectively) was taken into account and an effectiveness coefficient was
      determined for each adsorbent material. 

PMID- 26287830
TI  - Optimizing adsorption of Cr(VI) from aqueous solutions by NiO nanoparticles using
      Taguchi and response surface methods.
AB  - In the present study, nickel oxide nanoparticles synthesized by the sol-gel
      method were used as an effective adsorbent for the removal of Cr(VI) from aqueous
      solutions. To do so, the effect of four parameters including the concentration of
      Cr(VI), the dosage of NiO, contact time, and pH on the removal of Cr(VI) by NiO
      nanoparticles were studied. In order to examine and describe the optimum
      conditions for each of the mentioned parameters, Taguchi and response surface
      methods were used. The results of the experiment using Taguchi and response
      surface methods indicated the greater effect of the NiO adsorbent parameter in
      comparison to the other parameters in the adsorption of Cr(VI) by NiO
      nanoparticles, and showed that the increase in contact time and pH does not
      affect the removal percentage of Cr(VI) significantly. 

PMID- 26287831
TI  - Abatement vs. treatment for efficient diffuse source water pollution management
      in terrestrial-marine systems.
AB  - Marine ecosystems are affected by water pollution originating from coastal
      catchments. The delivery of water pollutants can be reduced through water
      pollution abatement as well as water pollution treatment. Hence, sustainable
      economic development of coastal regions requires balancing of the marginal costs
      from water pollution abatement and/or treatment and the associated marginal
      benefits from marine resource appreciation. Water pollution delivery reduction
      costs are, however, not equal across abatement and treatment options. In this
      paper, an optimal control approach is developed and applied to explore welfare
      maximizing rates of water pollution abatement and/or treatment for efficient
      diffuse source water pollution management in terrestrial-marine systems. For the
      case of diffuse source dissolved inorganic nitrogen water pollution in the Tully
      Murray region, Queensland, Australia, (agricultural) water pollution abatement
      cost, (wetland) water pollution treatment cost and marine benefit functions are
      determined to explore welfare maximizing rates of water pollution abatement
      and/or treatment. Considering partial (wetland) treatment costs and positive
      water quality improvement benefits, results show that welfare gains can be
      obtained, primarily, through diffuse source water pollution abatement (improved
      agricultural management practices) and, to a minor extent, through diffuse source
      water pollution treatment (wetland restoration). 

PMID- 26287832
TI  - Inhibition of biofouling by modification of forward osmosis membrane using
      quaternary ammonium cation.
AB  - In the operation of the forward osmosis (FO) process, biofouling of the membrane
      is a potentially serious problem. Development of an FO membrane with
      antibacterial properties could contribute to a reduction in biofouling. In this
      study, quaternary ammonium cation (QAC), a widely used biocidal material, was
      conjugated with a silane coupling agent (3-(trimethoxysilyl)
      propyldimethyloctadecyl ammonium chloride) and used to modify an FO membrane to
      confer antibacterial properties. Fourier transform infrared spectroscopy (FT-IR)
      demonstrated that the conjugated QAC was successfully immobilized on the FO
      membrane via covalent bonding. Bacterial viability on the QAC-modified membrane
      was confirmed via colony count method and visualized via bacterial viability
      assay. The QAC membrane decreased the viability of Escherichia coli to 62% and
      Staphylococcus aureus to 77% versus the control membrane. Inhibition of biofilm
      formation on the QAC modified membrane was confirmed via anti-biofilm tests using
      the drip-flow reactor and FO unit, resulting in 64% and 68% inhibition in the QAC
      modified membrane against the control membrane, respectively. The results
      demonstrate the effectiveness of the modified membrane in reducing bacterial
      viability and inhibiting biofilm formation, indicating the potential of QAC
      modified membranes to decrease operation costs incurred by biofouling. 

PMID- 26287833
TI  - Investigation of photo-assisted and crude peroxidase mediated transformations of
      chlorinated phenols (CPs) from spiked and industrial wastewaters: identification
      of reaction products.
AB  - This work focused on photo-assisted crude peroxidase mediated transformations of
      chlorinated phenols (CPs) from spiked and industrial wastewaters and the
      identification of reaction products formed. Garden radish Raphanus sativus was
      the source of crude peroxidase. No chlorine bearing compounds were detected by
      gas chromatography-high resolution mass spectrometry analysis. Under identical
      test conditions, the concentrations of 4-chlorophenol and 2,4-dichlorophenol were
      demoted to zero from 514 mg/L, 652 mg/L and that of 2,4,6-trichlorophenol and
      pentachlorophenol were reduced to 18 mg/L and 37 mg/L from 790 mg/L and 1066
      mg/L, respectively (high-pressure liquid chromatography analysis). Chloride ion
      release profiles also showed a progressively increasing trend. A neat chemical
      oxygen demand removal to the extent of 63-79% was achieved in the case of spiked
      wastewater sample and to the extent of 77% for industrial wastewaters. A
      hypothesis reaction scheme was also suggested to comprehend the mechanism of
      degradation reactions. 

PMID- 26287834
TI  - Bioaugmentation treatment of PV wafer manufacturing wastewater by microbial
      culture.
AB  - The wastewater of silicon photovoltaic (PV) battery manufacturing contained
      polyethylene glycol (PEG) and detergents, which possessed the characteristics of
      high content of organics and low bioavailability, and then resulted in high
      treatment costs. To address the difficulties of existing treatment facilities in
      stably meeting discharge standards, eight tons of microbial culture (consisting
      of Bacillus sp. and Rhodococcus sp.) were added into the aerobic treatment unit.
      Subsequently, the effectiveness of the microbial culture in small-scale
      biological wastewater treatment was evaluated, and the operating conditions for
      engineering applications were optimized. The application study showed that the
      average chemical oxygen demand (COD) removal efficiency reached 95.0% when the pH
      value was 7, the gas-water ratio was 28:1, the reflux ratio was 50%, which
      indicated an increase of 51.2% contrasting with the situation without
      bioaugmentation. The volume load of the treatment facilities after augmentation
      increased by 127.9% and could tolerate the COD shock load reached 2,340 mg.L(-1).
      At last, the effluence met the class I standard of the Integrated Wastewater
      Discharge Standard (GB8978-1996).

PMID- 26287835
TI  - Flotation of algae for water reuse and biomass production: role of zeta potential
      and surfactant to separate algal particles.
AB  - The effect of chemical coagulation and biological auto-flocculation relative to
      zeta potential was examined to compare flotation and sedimentation separation
      processes for algae harvesting. Experiments revealed that microalgae separation
      is related to auto-flocculation of Anabaena spp. and requires chemical
      coagulation for the whole period of microalgae cultivation. In addition,
      microalgae separation characteristics which are associated with surfactants
      demonstrated optimal microalgae cultivation time and separation efficiency of
      dissolved CO2 flotation (DCF) as an alternative to dissolved air flotation (DAF).
      Microalgae were significantly separated in response to anionic surfactant rather
      than cationic surfactant as a function of bubble size and zeta potential. DAF and
      DCF both showed slightly efficient flotation; however, application of anionic
      surfactant was required when using DCF. 

PMID- 26287836
TI  - Effects of mixed liquor pH on membrane fouling and micro-pollutant removals in
      membrane bioreactors for municipal landfill leachate treatment.
AB  - This research investigated the membrane fouling and micro-pollutant removals in
      treatment of municipal landfill leachate at various pH levels (i.e. 5.5, 6.5,
      7.5, and 8.5) using membrane bioreactors. The findings revealed that membrane
      fouling was influenced by the pH level of mixed liquor, with pH 5.5 exhibiting
      the most severe membrane fouling. At pH 5.5, proteins and carbohydrates were
      predominant in the membrane foulants, while at pH 8.5 humic-like and inorganic
      substances constituted the largest proportion of the foulants on the membrane
      surface. The removal efficiencies of micro-pollutants (bisphenol-A; 2,6-di-tert
      butylphenol and 2,6-di-tert-butyl-4-methylbutylphenol) were nevertheless
      insignificantly influenced by the pH levels of mixed liquor. In addition, the
      removal rates of the compounds at pH 5.5 were slightly lower vis-a-vis at the
      higher pH levels. The micro-pollutant retention on the fouled membranes was also
      significant and highest under the mixed liquor pH of 8.5. Furthermore, the
      experiments demonstrated that the varying degrees of rejection by the fouled
      membranes could be attributed to the alteration of foulant characteristics as a
      result of the pH variations. 

PMID- 26287837
TI  - Sorption of microconstituents onto primary sludge.
AB  - The presence of microconstituents (MCs) in the environment has become an emerging
      concern to scientists and engineers. Sorption is one of the important removal
      mechanisms for MCs in wastewater treatment plants (WWTPs) since there is
      significant sludge production. The purpose of this study is to explore sorption
      kinetics and isotherms of MCs onto primary sludge. Three MCs, bisphenol-A (BPA),
      17-alpha-ethinylestradiol (EE2) and triclosan (TCS), were chosen for this study.
      They are hydrophobic and have low vapor pressure, which makes sorption a
      potential removal mechanism. Both sorption kinetics and isotherm experiments were
      conducted using primary sludge collected from a local municipal WWTP. The time to
      equilibrium was around 7 h for all chosen MCs. A pseudo second-order rate model
      was better at describing the sorption rate than a pseudo first-order rate model.
      Linear sorption isotherm models were found to fit the experimental data, and the
      solid-liquid partitioning coefficients for BPA, EE2 and TCS were 81, 728 and
      6,407 L/kg. 

PMID- 26287838
TI  - Desalination of simulated seawater by purge-air pervaporation using an innovative
      fabricated membrane.
AB  - An innovative polymeric membrane has been invented, which presents a breakthrough
      in the field of desalination membranes. It can desalinate simulated seawater of
      exceptionally high concentration to produce a high flux of potable water with
      over 99.7% salt rejection (%SR) in a once-through purge-air pervaporation (PV)
      process. A set-up was constructed for conducting the desalination experiments and
      the effect of initial salt solution concentration (Ci) and pervaporation
      temperature (Tpv) on the water flux (J), %SR, separation factor, and
      pervaporation separation index were determined. The membrane was prepared by the
      phase-inversion technique, of a specially formulated casting solution consisting
      of five ingredients, after which the membrane was subjected to a post-treatment
      by which certain properties were conferred. The results confirmed that the
      salinity of the pervaporate was independent of Ci (all %SR above 99.7). The best
      result was at Tpv=70  degrees C, where J varied from 5.97 to 3.45 l/m2 h for
      Ci=40-140 g NaCl/l, respectively. The membrane morphology was confirmed to be
      asymmetric. The contact angle was immeasurable, indicating the membrane to be
      super-hydrophilic. Activation energies computed using Arrhenius law were, under
      all conditions investigated, less than 20 kJ/mol K.

PMID- 26287839
TI  - Decolorization and biogas production by an anaerobic consortium: effect of
      different azo dyes and quinoid redox mediators.
AB  - The inhibitory effect of azo dyes and quinoid compounds on an anaerobic
      consortium was evaluated during a decolorization process and biogas production.
      In addition, the impact of quinoid compounds such as lawsone (LAW) and
      anthraquinone-2,6-disulfonate (AQDS) on the rate of decolorization of Direct Blue
      71 (DB71) was assessed. The anaerobic consortium was not completely inhibited
      under all tested dye concentrations (0.1-2 mmol l(-1)), evidenced by an active
      decolorization process and biogas production. The presence of quinoid compounds
      at different concentrations (4, 8, and 12 mmol l(-1)) also inhibited biogas
      production compared to the control incubated without the quinoid compounds. In
      summary, the anaerobic consortium was affected to a greater extent by increasing
      the quantity of azo dyes or quinoid compounds. Nevertheless, at a lower
      concentration (1 mmol l(-1)) of quinoid compounds, the anaerobic consortium
      effectively decolorized 2 mmol l(-1) of DB71, increasing up to 5.2- and 20.4-fold
      the rate of decolorization with AQDS and LAW, respectively, compared to the
      control lacking quinoid compounds. 

PMID- 26287840
TI  - Removal of hydrocarbons from synthetic road runoff through adsorptive filters.
AB  - Compact filter systems, which are installed to significantly reduce the load of
      pollutants from road runoff, are very promising treatments for urban runoff. The
      objective of this research was to evaluate the effectiveness of activated carbon,
      activated lignite, zero valent iron, exfoliated graphite, amorphous ferric
      hydroxide, and activated alumina at removing petrol hydrocarbons from synthetic
      road runoff. Therefore, the kinetics and the equilibrium adsorption of petrol
      hydrocarbons onto these adsorbents were investigated using column adsorption
      experiments at levels ranging from 100 to 42 g L(-1). Of the tested adsorbents,
      exfoliated graphite is the most effective with a maximum adsorption capacity for
      petrol hydrocarbons of 3,850 mg g(-1). The experimental equilibrium data are
      fitted to the Freundlich and Langmuir models. 

PMID- 26287841
TI  - Examination of Pb2+ bio-sorption onto Rhodotorula mucilaginosa using response
      surface methodology.
AB  - With the rapid industrial development, wastewater has been a risk for
      environmental contamination. We aimed to explore the optimum condition and
      mechanism of Pb2+ bio-sorption onto Rhodotorula mucilaginosa WT6-5. Optimization
      of initial concentration of Pb2+, initial pH, and adsorption time for Pb2+ bio
      sorption onto R. mucilaginosa WT6-5 was performed using response surface
      methodology. Field emission scanning electron microscopy, energy dispersive X-ray
      detection, X-ray fluorescence and Fourier transform infrared spectroscopy were
      used to analyze the mechanisms and characteristics of Pb2+ bio-sorption. A
      maximum Pb2+ bio-sorption capacity of 1.45 mg/g was obtained under the optimal
      conditions of initial concentration of Pb2+ (30 mg/L), initial pH (5.45) and
      adsorption time (25 minutes). Some Pb2+ remained after adsorption, and the -OH, 
      C=O and C-O functional groups were primarily involved in Pb2+ bio-sorption onto
      R. mucilaginosa WT6-5. The mechanism of Pb2+ bio-sorption involved chemical and
      biological actions, ion exchange and functional groups effects.

PMID- 26287842
TI  - Vertical flow constructed wetlands subject to load variations: an improved design
      methodology connected to outlet quality objectives.
AB  - This study surveyed four campsites and four rural villages of major tourist
      interest, called tourist-interest or ti-villages, that were monitored for several
      years, generating over 70 performance balances for vertical flow constructed
      wetlands (VFCWs) that were intentionally scaled down for experimental trials. The
      wastewater effectively qualifies as domestic sewage, although relatively
      concentrated, with the campsites presenting particularly high nitrogen
      concentrations (122 gTKN L(-1)) (TKN: total Kjeldahl nitrogen). The applied daily
      loads were also particularly high, with some combinations of load parameters
      (hydraulic load, organic matter, TKN) leading to 400% overloading. Even under
      those drastic conditions, the quality of effluent remained excellent on the
      characteristic organic matter parameters, with removal performances always over
      85%. Analysis of the dataset points to two major design thresholds: for
      campsites, in order to maintain a 73% nitrification rate even at the height of
      the summer season, the load applied onto the first stage filter in operation
      could achieve up to 600 gCOD m(-2) day(-1) (COD: chemical oxygen demand). For
      tourist-interest villages, in order to maintain an 85% nitrification rate, the
      load applied onto the second stage filter in operation could achieve up to 22
      gTKN m(-2).day(-1). Here, VFCWs were demonstrated to robustly handle a massive
      increase in loads applied, providing the construction and operation stringently
      follow design standards and practices. 

PMID- 26287843
TI  - Distributions of phosphorus fractions in the sediments of a river-lake system: a
      case study in Huai River catchment area, China.
AB  - Phosphorus (P) forms, with respect to sediment characteristics, and an in-stream
      sluice were studied in the river-lake system, Huai River catchment area, China.
      The mean of total P in sediments in the mainstream of the Huai River was higher
      than that in the Hongze Lake. It was found that P fractions varied in the
      sediments throughout the river and lake. Detrital-P was the dominant P fraction
      in the mainstream and organic P and detrital-P were the dominant P fractions in
      the lake, which could indicate: biologically available and non-biologically
      available forms. Useful information for the interpretation of P fractions could
      also be obtained from major sediment characteristics. Whether the relations
      between P fractions and grain size characteristics were significant or weak,
      0.125 mm was a threshold grain size for P fraction distribution in sediment. In
      addition, the Bengbu Sluice, one of the most important in-stream facilities in
      the Huai River catchment area, regulated not only the transport of P in sediments
      upstream and downstream of the sluice, but also the distribution of P fractions
      in the river-lake system. Therefore, it was confirmed that nutrient loadings
      could be prevented from reaching the watershed, as well as improved ecological
      diversity by integrating sluice operation. 

PMID- 26287844
TI  - Erratum: Water Science and Technology 71 (8), 1241-1248: Long-term performance of
      side-stream deammonification in a continuous flow granular-activated sludge
      process for nitrogen removal from high ammonium wastewater, Babak Rezania, Donald
      S. Mavinic and Harlan G. Kelly.

PMID- 26287845
TI  - Role of dopamine D4 receptors in copulatory behavior: Studies with selective D4
      agonists and antagonists in male rats.
AB  - Dopamine influences the anticipatory and consummatory phases of sexual behavior,
      by acting on receptors of the D2 family (D2, D3 and D4) and in particular of the
      D2 subtype, although evidence for a role of D4 receptors in erectile function and
      copulatory behavior is also available. In order to clarify such a role of D4
      receptors, the effect of selective D4 receptor agonists and antagonists on
      copulatory behavior of sexually potent male rats in classic copulation tests with
      a receptive female, was compared with that of apomorphine and haloperidol, a
      classic dopamine receptor agonist and antagonist, respectively. PD-168,077 (0.05
      0.2mg/kg) and ABT-724 (0.01-0.04mg/kg), two selective D4 receptor agonists, given
      subcutaneously, improved dose-dependently copulatory behavior as shown by the
      decrease of mount frequency and post ejaculatory interval induced by PD-168,077,
      and of mount frequency, ejaculation latency, post ejaculatory and inter
      intromission intervals induced by ABT-724, and by the increase of ejaculation
      frequency and copulatory efficacy induced by both drugs. Conversely, L-745,870 (1
      5mg/kg), a selective D4 receptor antagonist, given intraperitoneally, impaired
      dose-dependently copulatory behavior, as shown by the increase in intromission
      and ejaculation latencies, mount frequency, post ejaculatory interval and the
      decrease in ejaculation frequency and copulatory efficacy induced by this drug. L
      745,870 (5mg/kg) administered before PD-168,077 (0.2mg/kg) or ABT-724
      (0.04mg/kg), also abolished completely the facilitatory effects of both PD
      168,077 and ABT-724 on sexual behavior. These results confirm the involvement of
      D4 receptors in specific aspects of male rat copulatory behavior that overlap
      only partially with those influenced by apomorphine and haloperidol. 

PMID- 26287846
TI  - Testosterone and "Age-Related Hypogonadism"--FDA Concerns.

PMID- 26287847
TI  - Let's Not Put All Our Eggs in One Basket.

PMID- 26287848
TI  - GMOs, Herbicides, and Public Health.

PMID- 26287851
TI  - IMAGES IN CLINICAL MEDICINE. Multiple Mucosal Neuroma.

PMID- 26287850
TI  - Palliative Care for the Seriously Ill.

PMID- 26287849
TI  - Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations.
AB  - BACKGROUND: BRAF V600 mutations occur in various nonmelanoma cancers. We
      undertook a histology-independent phase 2 "basket" study of vemurafenib in BRAF
      V600 mutation-positive nonmelanoma cancers. METHODS: We enrolled patients in six
      prespecified cancer cohorts; patients with all other tumor types were enrolled in
      a seventh cohort. A total of 122 patients with BRAF V600 mutation-positive cancer
      were treated, including 27 patients with colorectal cancer who received
      vemurafenib and cetuximab. The primary end point was the response rate; secondary
      end points included progression-free and overall survival. RESULTS: In the cohort
      with non-small-cell lung cancer, the response rate was 42% (95% confidence
      interval [CI], 20 to 67) and median progression-free survival was 7.3 months (95%
      CI, 3.5 to 10.8). In the cohort with Erdheim-Chester disease or Langerhans'-cell
      histiocytosis, the response rate was 43% (95% CI, 18 to 71); the median treatment
      duration was 5.9 months (range, 0.6 to 18.6), and no patients had disease
      progression during therapy. There were anecdotal responses among patients with
      pleomorphic xanthoastrocytoma, anaplastic thyroid cancer, cholangiocarcinoma,
      salivary-duct cancer, ovarian cancer, and clear-cell sarcoma and among patients
      with colorectal cancer who received vemurafenib and cetuximab. Safety was similar
      to that in prior studies of vemurafenib for melanoma. CONCLUSIONS: BRAF V600
      appears to be a targetable oncogene in some, but not all, nonmelanoma cancers.
      Preliminary vemurafenib activity was observed in non-small-cell lung cancer and
      in Erdheim-Chester disease and Langerhans'-cell histiocytosis. The histologic
      context is an important determinant of response in BRAF V600-mutated cancers.
      (Funded by F. Hoffmann-La Roche/Genentech; ClinicalTrials.gov number,
      NCT01524978.).

PMID- 26287852
TI  - CASE RECORDS of the MASSACHUSETTS GENERAL HOSPITAL. Case 26-2015. A 9-Month-Old
      Girl with Recurrent Fevers.

PMID- 26287853
TI  - Viral Vectors Take On HIV Infection.

PMID- 26287854
TI  - PCSK9 Inhibitors and Cardiovascular Events.

PMID- 26287855
TI  - PCSK9 Inhibitors and Cardiovascular Events.

PMID- 26287856
TI  - PCSK9 Inhibitors and Cardiovascular Events.

PMID- 26287857
TI  - Chimpanzee Adenovirus Vector Ebola Vaccine--Preliminary Report.

PMID- 26287858
TI  - Chimpanzee Adenovirus Vector Ebola Vaccine--Preliminary Report.

PMID- 26287859
TI  - Performance in Year 1 of Pioneer Accountable Care Organizations.

PMID- 26287860
TI  - Performance in Year 1 of Pioneer Accountable Care Organizations.

PMID- 26287861
TI  - Conflicts of Interest.

PMID- 26287862
TI  - Conflicts of Interest.

PMID- 26287863
TI  - Conflicts of Interest.

PMID- 26287864
TI  - Conflicts of Interest.

PMID- 26287865
TI  - Conflicts of Interest.

PMID- 26287867
TI  - Efficacy and Safety of Nintedanib in Idiopathic Pulmonary Fibrosis.

PMID- 26287866
TI  - Mesenteric Ischemia Mimicking ST-Segment Elevation Myocardial Infarction.

PMID- 26287868
TI  - A Dominant-Negative GFI1B Mutation in the Gray Platelet Syndrome.

PMID- 26287869
TI  - Dependent Coverage and Use of Preventive Care under the Affordable Care Act.

PMID- 26287870
TI  - IMAGES IN CLINICAL MEDICINE. Electrical Alternans with Pericardial Tamponade.

PMID- 26287871
TI  - VIDEOS IN CLINICAL MEDICINE. Examination of the Retina.

PMID- 26287873
TI  - Optical biometry: every little bit helps.

PMID- 26287874
TI  - Robert M. Sinskey, MD: Ophthalmic Surgeon, Innovator, Teacher, and Oenophile.

PMID- 26287872
TI  - Monoacylglycerol Lipase Regulates Fever Response.
AB  - Cyclooxygenase inhibitors such as ibuprofen have been used for decades to control
      fever through reducing the levels of the pyrogenic lipid transmitter
      prostaglandin E2 (PGE2). Historically, phospholipases have been considered to be
      the primary generator of the arachidonic acid (AA) precursor pool for generating
      PGE2 and other eicosanoids. However, recent studies have demonstrated that
      monoacyglycerol lipase (MAGL), through hydrolysis of the endocannabinoid 2
      arachidonoylglycerol, provides a major source of AA for PGE2 synthesis in the
      mammalian brain under basal and neuroinflammatory states. We show here that
      either genetic or pharmacological ablation of MAGL leads to significantly reduced
      fever responses in both centrally or peripherally-administered lipopolysaccharide
      or interleukin-1beta-induced fever models in mice. We also show that a
      cannabinoid CB1 receptor antagonist does not attenuate these anti-pyrogenic
      effects of MAGL inhibitors. Thus, much like traditional nonsteroidal anti
      inflammatory drugs, MAGL inhibitors can control fever, but appear to do so
      through restricted control over prostaglandin production in the nervous system. 

PMID- 26287875
TI  - Simple approach to prevent capsule tear-out during capsulorhexis creation in
      hypermature cataracts.
AB  - Capsule tear-out in hypermature cataracts (Argentinean flag sign) is a common and
      frustrating complication during the creation of a capsulorhexis. Completing the
      capsulorhexis through a small side-port incision, filling the anterior chamber
      with a highly viscous ophthalmic viscosurgical device such as a viscoadaptive
      agent, and using a 23- or 25-gauge microcapsulorhexis forceps to fill the side
      port incision can reliably prevent this complication. FINANCIAL DISCLOSURE:
      Neither author has a financial or proprietary interest in any material or method
      mentioned.

PMID- 26287876
TI  - Comparison of visual recovery and refractive stability between femtosecond laser
      assisted cataract surgery and standard phacoemulsification: six-month follow-up.
AB  - PURPOSE: To compare visual recovery and refractive changes between femtosecond
      laser-assisted cataract surgery and standard cataract surgery. SETTING: Center
      for Vision Science, Ruhr University Eye Clinic, Bochum, Germany. DESIGN:
      Prospective randomized intraindividual cohort study. METHODS: Eyes were treated
      with femtosecond laser-assisted cataract surgery or conventional
      phacoemulsification using pulsed ultrasound energy. Both groups had intraocular
      lens (IOL) implantation. The manifest refraction, corrected distance visual
      acuity, and anterior chamber depth were determined preoperatively and 2 hours, 3
      to 4 days, 1 week, and 1, 2, 3, and 6 months postoperatively to determine the
      achieved deviation from target refraction, IOL position, and refractive
      stability. RESULTS: One hundred eyes of 100 patients were treated with
      femtosecond laser-assisted cataract surgery; the fellow 100 eyes had conventional
      phacoemulsification. Six months postoperatively, 196 eyes were included and
      analyzed. At 6 months, 90 eyes (92%) in the femtosecond laser-assisted group and
      70 eyes (71%) in the conventional group were within +/-0.50 D of the target
      refractive outcome and 98 eyes (100%) in both groups were within +/-1.00 D. The
      mean refractive spherical equivalent showed no significant change between 1 week
      and 1 month in the femtosecond laser-assisted group and between 1, 2, 3, and 6
      months postoperatively in both groups. CONCLUSION: Femtosecond laser-assisted
      cataract surgery yielded faster visual recovery, less deviation from the target
      refraction, and earlier stabilization of refraction. FINANCIAL DISCLOSURE: Dr.
      Dick is a member of the medical advisory board of Abbott Medical Optics, Inc. No
      other author has a financial or proprietary interest in any material or method
      mentioned.

PMID- 26287877
TI  - Comparison of the predictability of refractive cylinder correction by laser in
      situ keratomileusis in eyes with low or high ocular residual astigmatism.
AB  - PURPOSE: To compare the manifest refractive cylinder (MRC) predictability of
      myopic astigmatism laser in situ keratomileusis (LASIK) between eyes with low and
      high ocular residual astigmatism (ORA). SETTING: London Vision Clinic, London,
      United Kingdom. DESIGN: Retrospective case study. METHODS: The ORA was considered
      the vector difference between the MRC and the corneal astigmatism. The index of
      success (IoS), difference vector / MRC, was analyzed for different groups as
      follows: stage 1, low ORA (ORA / MRC <1), high ORA (ORA / MRC >=1); stage 2, low
      ORA group reduced to match the high ORA group for MRC; stage 3, grouped by ORA
      magnitude with low ORA (<0.50 diopters [D]), mid ORA (0.50 to 1.24 D), and high
      ORA (>=1.25 D); stage 4, high ORA group subdivided into low (<0.75 D) and high
      (>=0.75 D) corneal astigmatism. RESULTS: For stage 1, the mean preoperative MRC
      and mean IoS were -1.32 D +/- 0.65 (SD) (range -0.55 to -3.77 D) and 0.27,
      respectively, for low ORA and -0.79 +/- 0.20 D (range -0.56 to -2.05 D) and 0.37,
      respectively, for high ORA. For stage 2, the mean IoS increased to 0.32 for low
      ORA. For stage 3, the mean IoS was 0.28, 0.29, and 0.31 for low ORA, mid ORA, and
      high ORA, respectively. For stage 4, the mean IoS was 0.20 for high ORA/low
      corneal astigmatism and 0.35 for high ORA/high corneal astigmatism. CONCLUSIONS:
      The MRC predictability was slightly worse in eyes with high ORA when grouped by
      the ORA / MRC. Matching for the MRC and grouping by ORA magnitude resulted in
      similar predictability; however, eyes with high ORA and high corneal astigmatism
      were less predictable. FINANCIAL DISCLOSURE: Dr. Reinstein is a consultant to
      Carl Zeiss Meditec AG, has a proprietary interest in the Artemis technology
      (Arcscan, Inc.), and is an author of patents related to very-high-frequency
      digital ultrasound administered by the Center for Technology Licensing at Cornell
      University, Ithaca, New York, USA. No other author has a financial or proprietary
      interest in any material or method mentioned.

PMID- 26287878
TI  - Fibrin adhesive in conjunction with epithelial ingrowth removal after laser in
      situ keratomileusis: long-term results.
AB  - PURPOSE: To describe the long-term results of fibrin adhesive use in the
      management of epithelial ingrowth after laser in situ keratomileusis (LASIK).
      SETTING: Private practice, Minneapolis, Minnesota, and an academic medical
      center, Durham, North Carolina, USA. DESIGN: Retrospective case series. METHODS:
      Patients with a history of LASIK had epithelial ingrowth removal with mechanical
      debridement and fibrin glue application. Visual outcomes and the presence or
      absence of epithelial ingrowth were evaluated again after 3 months and at the
      last follow-up. The main outcome measures were recurrence of epithelial ingrowth
      and visual acuity. RESULTS: Thirty-nine eyes of 38 patients were evaluated. After
      epithelial ingrowth removal and application of fibrin glue, 31 eyes (79.5%) had
      no recurrence of ingrowth at the final follow-up and 5 eyes (12.8%) had mild
      epithelial ingrowth not requiring removal. Three eyes (7.7%) had significant
      epithelial ingrowth at the 3-month follow-up that required subsequent removal and
      fibrin application. At the 3-month follow-up visit, 76.9% of eyes achieved 20/25
      or better corrected distance visual acuity (CDVA) and 69.2% of eyes achieved
      20/40 or better uncorrected distance visual acuity (UDVA). At the last follow-up
      visit (mean 26.6 +/- 17.0 months [SD]), 84.6% of eyes had 20/25 or better CDVA
      and 74.4% of eyes had 20/40 or better UDVA. CONCLUSIONS: Fibrin adhesive in
      conjunction with manual epithelial removal prevented a clinically significant
      recurrence of epithelial ingrowth in the majority of eyes. Larger randomized
      studies are needed to compare the success of this technique with that of others.
      FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any
      material or method mentioned.

PMID- 26287879
TI  - Ocular straylight in the normal pseudophakic eye.
AB  - PURPOSE: To assess normal values for straylight in the pseudophakic eye as a
      function of age and to develop a model to predict the improvement in straylight
      after lens extraction based on preoperative straylight levels. SETTING: Rotterdam
      Ophthalmic Institute, Rotterdam, the Netherlands. DESIGN: Review with
      retrospective cross-study analysis. METHODS: A literature review was performed to
      identify relevant papers on straylight and pseudophakia with no patient
      comorbidities. Sixteen papers met the eligibility criteria and were included in
      the analysis. The postoperative results were used to define the norm for
      straylight in pseudophakia. Straylight improvement after lens replacement was
      assessed by evaluation of preoperative and postoperative values. The age effect
      was incorporated to determine a model for straylight improvement. RESULTS: The
      mean postoperative straylight value derived from 16 studies (1869 eyes) was 1.21
      log units +/- 0.21 (SD). Age dependence could be assessed from 13 studies (1533
      eyes), resulting in the straylight age-norm curve in pseudophakic eyes as
      follows: Straylight value = 0.0044 * age + 0.89 with +/- 0.42 log units of 95%
      confidence interval. A strong correlation was observed between preoperative
      straylight and its improvement after lens extraction, yielding the following
      relationship: Straylight improvement = 1.04 * preoperative straylight value -
      0.006 * age - 0.84. CONCLUSION: A norm for straylight in the pseudophakic eye was
      developed that is considerably different from the previously published norm for
      the phakic eye. The new pseudophakic norm can be used clinically to predict the
      straylight value after lens replacement and as a reference criterion for clinical
      studies. FINANCIAL DISCLOSURE: The Netherlands Academy of Arts and Sciences owns
      a patent on straylight measurement, with Dr. van den Berg as the inventor, and
      licenses that to Oculus Optikgerate GmbH for the C-Quant instrument. No author
      has a financial or proprietary interest in any material or method mentioned.

PMID- 26287880
TI  - Transepithelial versus epithelium-off crosslinking in adults with progressive
      keratoconus.
AB  - PURPOSE: To compare the efficacy of epithelium-off corneal collagen crosslinking
      (CXL) with transepithelial CXL in patients with progressive keratoconus. SETTING:
      Department of Ophthalmology, Marmara University School of Medicine, Istanbul,
      Turkey. DESIGN: Retrospective cohort study. METHODS: Eyes that had
      transepithelial CXL were compared with eyes treated with epithelium-off CXL. All
      patients with a follow-up of 18 months were evaluated for uncorrected (UDVA) and
      corrected (CDVA) distance visual acuities, corneal topography, aberrometry, and
      pachymetry (Pentacam). RESULTS: The mean patient age was 22.8 years +/- 4.7 (SD)
      (range 18 to 31 years) in the transepithelial group (30 eyes) and 23.7 +/- 3.9
      years (range 18 to 30 years) in the epithelium-off group (30 eyes). The mean UDVA
      and CDVA significantly improved in both groups (P < .001). There was no
      significant difference in the CDVA gain between the 2 groups. In the epithelium
      off group, significant improvements occurred in spherical error (P = .002),
      spherical equivalent (P = .004), maximum keratometry (K), flat K (P = .036), and
      steep K (P < .001). The reductions in flat K, steep K, and maximum K were greater
      in the epithelium-off group (P = .004 for flat K; P < .001 for steep K and
      maximum K). In the transepithelial group, significant improvements occurred in
      the cylindrical error (P = .009) and in the index of surface variance and index
      of surface asymmetry (both P < .001). CONCLUSION: Although transepithelial CXL
      seemed to have reduced effectiveness in inducing improvement in topographic
      indices, its effect on visual acuity is likely to be similar to that of
      epithelium-off CXL. FINANCIAL DISCLOSURE: No author has a financial or
      proprietary interest in any material or method mentioned.

PMID- 26287881
TI  - Combined laser in situ keratomileusis and prophylactic high-fluence corneal
      collagen crosslinking for high myopia: two-year safety and efficacy.
AB  - PURPOSE: To evaluate the safety, efficacy, and refractive and keratometric
      stability of myopic femtosecond laser in situ keratomileusis (LASIK) with
      concurrent prophylactic high-fluence corneal collagen crosslinking (CXL) compared
      with the outcomes of standard femtosecond LASIK. SETTING: Private clinical
      practice, Athens, Greece. DESIGN: Consecutive randomized prospective comparative
      study. METHODS: Eyes that had myopic LASIK or myopic LASIK with concurrent high
      fluence CXL were evaluated preoperatively and up to 2 years postoperatively for
      manifest refraction spherical equivalent (MRSE), refractive astigmatism, visual
      acuity, corneal keratometry (K), and endothelial cell count. RESULTS: One hundred
      forty consecutive eyes had myopic LASIK; 65 of the eyes were treated additionally
      with CXL. In the LASIK-CXL eyes, the mean postoperative MRSE was -0.18 diopter
      (D) +/- 17.0 (SD) from -6.67 +/- 2.14 D preoperatively. The postoperative flat K
      was 37.67 D from 43.92 D, and the steep K was 38.38 D from 45.15 D. The
      correlation coefficient of SE correction predictability was 0.975. In the LASIK
      only eyes, the mean postoperative MRSE was -0.32 +/- 0.24 D from -5.49 +/- 1.99 D
      preoperatively. The flat K was 38.04 D from 43.15 D, and the steep K was 38.69 D
      from 44.03 D. The correlation coefficient of SE correction predictability was
      0.968. The differences between the 2 groups at the 20/20 and 20/25 levels were
      statistically significant (P = .045 and P = .039, respectively). CONCLUSION: Two
      year results indicate that the application of prophylactic CXL concurrently with
      high-myopic LASIK appears to improve refractive and keratometric stability,
      presumably by affecting corneal biomechanical properties. FINANCIAL DISCLOSURE:
      Dr. Kanellopoulos is a consultant to Alcon Surgical, Inc., Wavelight Laser
      Technologie AG, Allergan, Inc., Avedro, Inc., and i-Optics Corp. Dr. Asimellis
      has no financial or proprietary interest in any material or method mentioned.

PMID- 26287882
TI  - Aspheric versus wavefront-guided photorefractive keratectomy: contralateral eye
      study.
AB  - PURPOSE: To compare the refractive, visual, and aberrometric outcomes between
      wavefront-guided photorefractive keratectomy (PRK) and aspheric PRK in myopic
      patients. SETTING: Khatam-al-Anbia Eye Hospital, Mashhad, Iran. DESIGN:
      Prospective randomized clinical trial. METHODS: One eye of each patient was
      randomly assigned to excimer laser wavefront-guided PRK (Zyoptix) and the other
      eye to excimer laser aspheric PRK (Technolas 217z). The preoperative and 3-month
      and 6-month postoperative refractive errors, visual acuity, contrast sensitivity,
      and higher-order aberrations (HOAs) were compared between the groups. RESULTS:
      Ninety-six eyes (48 patients) were enrolled. At the last postoperative visit,
      there were no between-group differences in uncorrected distance visual acuity
      (UDVA) (P = .987) or corrected distance visual acuity (P = .416). The mean
      spherical equivalent was -0.076 diopter (D) +/- 0.029 (SD) in the wavefront
      guided group and -0.077 +/- 0.075 D in the aspheric PRK group (P = .684).
      Postoperatively, the mean area under the log of contrast sensitivity function
      (AULCSF) with and without glare testing improved over preoperative values (both P
      < .001). There was no statistically significant between-group difference in the
      AULCSF with glare (P = .903) or without glare (P = .978). Total HOAs increased
      after PRK in both groups, although aspheric PRK induced fewer HOAs than wavefront
      guided PRK (P = .04). CONCLUSIONS: Both PRK methods equally improved
      postoperative UDVA and contrast sensitivity. The HOAs increased after treatment
      with both methods; however, aspheric ablation induced statistically fewer HOAs
      than wavefront-guided ablation. FINANCIAL DISCLOSURE: No author has a financial
      or proprietary interest in any material or method mentioned.

PMID- 26287883
TI  - Photorefractive keratectomy in 22 adult eyes with infantile nystagmus syndrome.
AB  - PURPOSE: To analyze visual and refractive outcomes of photorefractive keratectomy
      (PRK) in adult patients with infantile nystagmus syndrome. SETTING: Ophthalmology
      Unit, Department of Experimental Diagnostic and Specialty Medicine, Saint Orsola
      Malpighi Hospital, University of Bologna, Bologna, Italy. DESIGN: Retrospective
      case series. METHODS: Photorefractive keratectomy was performed in both eyes of
      patients with infantile nystagmus syndrome under topical anesthesia using an eye
      tracking excimer laser. Patient satisfaction was tested using a questionnaire.
      The main outcomes were a decrease in refractive error, an improvement in
      postoperative corrected distance visual acuity (CDVA), and an uncorrected
      distance visual acuity (UDVA) equal to or better than the preoperative UDVA.
      RESULTS: Twenty-two eyes of 11 patients with infantile nystagmus syndrome were
      evaluated. The mean patient age was 30.82 years (range 22 to 42 years). All eyes
      had simple, compound, or mixed astigmatism (mean -3.40 D; range -0.75 to -6.00
      diopters [D]). The mean postoperative astigmatism (-0.70 D +/- 0.81 [SD]) and
      spherical equivalent (-0.420 +/- 0.652 D) were statistically significantly better
      than the preoperative values (-3.40 +/- 1.31 D and -3.426 +/- 3.343 D,
      respectively (P < .0001 and P = .0002, respectively). The mean monocular
      postoperative CDVA (0.24 +/- 0.19 logMAR) and UDVA (0.25 +/- 0.18 logMAR) were
      better than the mean preoperative CDVA (0.32 +/- 0.28 logMAR) (P = .0045 and P =
      .0338, respectively). The mean binocular postoperative UDVA was better than the
      mean preoperative CDVA (0.15 +/- 0.14 logMAR versus 0.23 +/- 0.23 logMAR) (P =
      .05). No patient required repeat surgery. CONCLUSIONS: Nystagmus patients are
      eligible for PRK. The results were promising; gaining a few Snellen lines in
      visual acuity can be very important to these patients for their daily life.
      FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any
      material or method mentioned.

PMID- 26287884
TI  - Pars plana vitrectomy and iris suture fixation of posteriorly dislocated
      intraocular lenses.
AB  - PURPOSE: To describe the outcomes of combined pars plana vitrectomy (PPV) and
      iris suture fixation of posteriorly dislocated intraocular lenses (IOLs).
      SETTING: Tertiary academic referral center. DESIGN: Retrospective noncomparative
      consecutive case series. METHODS: The included eyes had posteriorly dislocated
      IOLs and had combined PPV and iris suture fixation. The IOL dislocations amenable
      to surgical repair with an anterior approach were excluded. Outcome measures
      included improvement in corrected distance visual acuity (CDVA), induction of
      astigmatism, and complications. RESULTS: This study consisted of 27 consecutive
      cases. The mean follow-up was 6.61 months +/- 8.1 (SD). The median postoperative
      CDVA was 20/30, and 16 of 27 eyes had stable or improved CDVA compared with
      baseline; 8 of the others had a shift from aphakic to pseudophakic correction.
      Overall, a significant myopic shift in spherical equivalent occurred after
      surgery, from 7.62 +/- 4.38 diopters (D) to -1.33 +/- 1.45 D (P < .001).
      Surgically induced astigmatism (SIA) assessed by comparing the difference in
      preoperative keratometry readings with the difference in postoperative manifest
      refraction cylinder adjusted to the corneal plane gave the following: 1.89 +/-
      1.09 D versus 1.13 +/- 0.86 D, respectively (P < .001). All IOLs were stable and
      centered at the last follow-up; however, 1 was mildly tilted. One eye had a
      recurrent subluxation, and the IOL was resutured before the end of the study. No
      cases of endophthalmitis or retinal detachment occurred. CONCLUSION: Combined PPV
      and iris suture fixation of posteriorly dislocated IOLs led to stable fixation of
      the IOLs. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest
      in any material or method mentioned.

PMID- 26287885
TI  - Reliability and reproducibility of the German version of the European Society of
      Cataract and Refractive Surgeons reading charts.
AB  - PURPOSE: To create a validated, standardized, logarithmic European Society of
      Cataract and Refractive Surgeons (ESCRS) reading chart in German and to use this
      reading chart as a template for comparable reading charts in other languages.
      SETTING: Hanusch Hospital, Vienna, and Department of Ophthalmology, Paracelsus
      Medical University, Salzburg, Austria. DESIGN: Prospective multicenter validation
      study. METHODS: Thirty-nine short standardized German sentences were developed
      and tested on healthy volunteers and pseudophakic patients. On the first visit,
      corrected distance visual acuity was assessed in each eye using autorefraction
      (KR8000) and subjective refraction using Early Treatment Diabetic Retinopathy
      Study charts at 4 m. Reading speed, when reading the new ESCRS reading charts,
      was tested under photopic conditions (85 to 100 candelas/m(2)) and high contrast
      (>=95% Michelson contrast). RESULTS: The study assessed 120 subjects. Sixty
      subjects were young healthy volunteers and 60 were pseudophakic patients.
      Reliability of the sentences was tested using Cronbach's alpha and was found to
      be high (alpha = 0.994). Furthermore, reproducibility was high in most cases and
      the absolute mean difference between the first measurement and second measurement
      for all sentences was 0.56 seconds +/- 0.07 (SD) (range 0.43 to 0.72 seconds).
      CONCLUSION: The German version of the ESCRS reading charts, a standardized
      logarithmic and validated reading test, was reliable in healthy volunteers as
      well as in pseudophakic patients. FINANCIAL DISCLOSURE: No author has a financial
      or proprietary interest in any material or method mentioned.

PMID- 26287886
TI  - Clinical outcomes of clear lens extraction in eyes with primary angle closure.
AB  - PURPOSE: To evaluate the effect of clear lens extraction (CLE) on intraocular
      pressure (IOP) and the anterior chamber angle in primary angle closure after
      laser peripheral iridotomy (LPI). SETTING: Tertiary eyecare center at a
      university hospital, New Delhi, India. DESIGN: Prospective case series. METHODS:
      The study included eyes with primary angle closure and an IOP over 25.0 mm Hg
      more than 8 weeks after LPI. All eyes had CLE by phacoemulsification. Absolute
      success was defined as an IOP less than 18.0 mm Hg without medications at 12
      months. RESULTS: In 44 eyes (24 women, 20 men; mean age 57.2 years +/- 4.2 [SD]),
      the mean preoperative IOP of 27.1 +/- 1.55 mm Hg decreased to 13.2 +/- 1.12 mm Hg
      at 12 months (P < .0001). The angle opening distance at 500 MUm increased from
      baseline values at 0 degrees (from 0.104 +/- 0.015 mm to 0.31 +/- 0.013 mm) and
      180 degrees (from 0.202 +/- 0.008 mm to 0.412 +/- 0.012 mm). The trabecular iris
      angle also increased at 0 degrees (from 9.3 +/- 3.2 degrees to 32.7 +/- 5.6
      degrees) and 180 degrees (from 9.12 +/- 3.2 degrees to 31.7 +/- 5.6 degrees) (all
      P < .0001). In multivariate analysis, the preoperative IOP was the strongest
      determinant of IOP change (R(2) = 0.69, P < .0001). Absolute success was achieved
      in 38 eyes (86.3%). CONCLUSION: Clear lens extraction led to a significant
      reduction in IOP, a widening of the anterior chamber angle, and a reduced need
      for ocular hypotensive medications in eyes with primary angle closure and
      persistently raised IOP after LPI. FINANCIAL DISCLOSURE: No author has a
      financial or proprietary interest in any material or method mentioned.

PMID- 26287887
TI  - Double-C loop platform in combination with hydrophobic and hydrophilic acrylic
      intraocular lens materials.
AB  - PURPOSE: To analyze the behavior of a new double-C-loop quadripod symmetrical
      intraocular lens (IOL) platform combined with a hydrophilic lens material and a
      new hydrophobic glistening-free acrylic lens material, Ankoris and Podeye,
      respectively, in silico (computer simulation), in vitro (laboratory
      investigation), and in vivo (rabbit model). SETTING: John A. Moran Eye Center,
      University of Utah, Salt Lake City, Utah, USA, and Physiol S.A., Liege, Belgium.
      DESIGN: Experimental study. METHODS: An in silico simulation investigation was
      performed using finite elements software, an in vitro investigation according to
      the International Organization for Standardization (ISO11979-3:2012), and an in
      vivo implantation in a rabbit model with 4 weeks of follow-up. Postmortem data
      were collected by Miyake-Apple gross examination and histopathologic analyses.
      Biocompatibility and IOL centration were tested. RESULTS: Both IOLs demonstrated
      statistically insignificant variations in posterior and anterior capsule
      opacification and Soemmerring ring formation. They were well biotolerated with no
      signs of toxicity, inflammation, or neovascularization. Axial and centration
      stability were noted in vitro and in vivo as a result of significant contact
      between surrounding tissues and haptics and the posterior portion of the optic.
      CONCLUSION: The results suggest suitability of the double-C loop IOL platform for
      the manufacturing of premium (ie, multifocal, toric, and multifocal toric) IOLs.
      FINANCIAL DISCLOSURE: Drs. Bozukova, Gobin, and Pagnoulle are employees of
      Physiol S.A., Liege, Belgium. Dr. Pagnoulle has a proprietary interest in the
      tested intraocular lenses. No other author has a financial or proprietary
      interest in any material or method mentioned.

PMID- 26287888
TI  - Mydriatic insert and intracameral injections compared with mydriatic eyedrops in
      cataract surgery: controlled studies.
AB  - Mydriatic eyedrops are the standard method for pupil dilation in cataract
      surgery, but their limitations have prompted a search for alternative techniques.
      Two alternatives-an ophthalmic insert containing phenylephrine and tropicamide
      and intracameral injections of various combinations of lidocaine, cyclopentolate,
      and phenylephrine, with or without epinephrine in the irrigating solution-have
      been assessed in prospective controlled studies, including randomized controlled
      trials (RCTs). We reviewed the safety and efficacy of mydriatic ophthalmic
      inserts and intracameral mydriatic injections compared with the safety and
      efficacy of mydriatic eyedrops using a systematic PubMed search (1963 to 2014).
      We identified 9 prospective studies (7 RCTs, 637 patients) of the mydriatic
      ophthalmic insert and 15 prospective studies (14 RCTs, 1020 patients) of
      intracameral mydriatic injections; 7 of the RCTs compared intracameral mydriatic
      injections and mydriatic eyedrops and 7 RCTs studied the optimum intracameral
      mydriatic injection protocol. The latter showed that a lidocaine and
      phenylephrine-based solution, without irrigating epinephrine, was optimum for
      intracameral mydriatic injections. The mydriatic ophthalmic insert and
      intracameral mydriatic injections were consistently shown to be safe and as
      effective as mydriatic eyedrops. Each method has distinct advantages and
      limitations. FINANCIAL DISCLOSURE: Dr. Behndig has received fees from Thea Pharma
      GmbH as a member of the European Team for the Prophylaxis of Infection in
      Cataract Surgery group. Dr. Korobelnik has received consultancy fees from Alcon
      Surgical, Inc.; Allergan, Inc.; Alimera, Inc.; Bayer HealthCare AG; Carl Zeiss
      Meditec AG; Novartis Corp.; Roche Innovatis AG; and Thea Pharma GmbH.

PMID- 26287889
TI  - Persistent anterior chamber silicone oil and myopia.
AB  - A 60-year-old man experienced a marked unilateral myopic shift of 20 diopters
      following attempted removal of intravitreal heavy silicone oil used in the
      treatment of inferior proliferative vitreoretinopathy following retinal
      detachment. Examination revealed heavy silicone oil adherent to the corneal
      endothelium and forming a convex interface with the aqueous, obscuring the entire
      pupil. Surgical intervention was required to restore visual acuity. The case
      highlights the potential ocular complications associated with silicone oil
      migration into the anterior chamber, including corneal endothelial decompensation
      and a significant increase in myopia. FINANCIAL DISCLOSURE: No author has a
      financial or proprietary interest in any material or method mentioned.

PMID- 26287890
TI  - Inadequate femtosecond laser-assisted corneal incision caused by reference ink
      mark.

PMID- 26287891
TI  - Resident training in femtosecond laser-assisted cataract surgery: national
      survey.

PMID- 26287892
TI  - Modified side-based scleral flap for intrascleral intraocular lens fixation.

PMID- 26287893
TI  - Postoperative spectral-domain optical coherence tomography evaluation of pre
      Descemet endothelial keratoplasty grafts.

PMID- 26287894
TI  - July consultation #2.

PMID- 26287895
TI  - Juvenile Glaucoma: At the Crossroads of Microinvasive and Traditional Glaucoma
      Surgeries: July consultation #1.

PMID- 26287896
TI  - July consultation #3.

PMID- 26287897
TI  - July consultation #4.

PMID- 26287898
TI  - July consultation #5.

PMID- 26287899
TI  - July consultation #6.

PMID- 26287900
TI  - July consultation #7.

PMID- 26287901
TI  - July consultation #8.

PMID- 26287902
TI  - July consultation #9.

PMID- 26287903
TI  - Reply: To PMID 25840295.

PMID- 26287904
TI  - Ophthalmic viscosurgical device choice in intumescent cataract.

PMID- 26287905
TI  - No-anesthesia cataract surgery.

PMID- 26287906
TI  - Reply: To PMID 25840296.

PMID- 26287907
TI  - Ophthalmic viscosurgical devices for intumescent cataracts: pressure-equalized
      cataract surgery.

PMID- 26287908
TI  - Reply: To PMID 25840295.

PMID- 26287909
TI  - Corneal ectasia after femtosecond laser-assisted small-incision lenticule
      extraction in eyes with subclinical keratoconus/forme fruste keratoconus.

PMID- 26287910
TI  - Unusual corneal ring.

PMID- 26287911
TI  - Reply: To PMID 25747164.

PMID- 26287912
TI  - Effect of corneal asphericity and spherical aberration on intraocular lens power
      calculations.

PMID- 26287913
TI  - Reply: To PMID 25840302.

PMID- 26287914
TI  - Driver Gaze Behavior Is Different in Normal Curve Driving and when Looking at the
      Tangent Point.
AB  - Several steering models in the visual science literature attempt to capture the
      visual strategies in curve driving. Some of them are based on steering points on
      the future path (FP), others on tangent points (TP). It is, however, challenging
      to differentiate between the models' predictions in real-world contexts. Analysis
      of optokinetic nystagmus (OKN) parameters is one useful measure, as the different
      strategies predict measurably different OKN patterns. Here, we directly test this
      prediction by asking drivers to either a) "drive as they normally would" or b) to
      "look at the TP". The design of the experiment is similar to a previous study by
      Kandil et al., but uses more sophisticated methods of eye-movement analysis. We
      find that the eye-movement patterns in the "normal" condition are indeed markedly
      different from the "tp" condition, and consistent with drivers looking at
      waypoints on the future path. This is the case for both overall fixation
      distribution, as well as the more informative fixation-by-fixation analysis of
      OKN. We find that the horizontal gaze speed during OKN corresponds well to the
      quantitative prediction of the future path models. The results also definitively
      rule out the alternative explanation that the OKN is produced by an involuntary
      reflex even while the driver is "trying" to look at the TP. The results are
      discussed in terms of the sequential organization of curve driving. 

PMID- 26287915
TI  - The Global Surgery Partnership: An Innovative Partnership for Education,
      Research, and Service.
AB  - PROBLEM: An estimated two billion people worldwide lack access to adequate
      surgical care. Addressing surgical disparities requires both immediate relief
      efforts and long-term investments to improve access to care and surgical
      outcomes, train the next generation of surgical professionals, and expand the
      breadth of formative research in the field. While models exist for establishing
      short-term surgical missions in low- and middle-income countries, far less focus
      has been placed on models for multi-institutional partnerships that support the
      development of sustainable solutions. APPROACH: In 2011, the Global Surgery
      Partnership (GSP) was founded by an established children's hospital (Children's
      Hospital Los Angeles), an academic medical center (University of Southern
      California), and a nonprofit organization (Operation Smile) to build oral cleft
      surgical capacity in resource-poor settings through education, research, and
      service. OUTCOMES: Leveraging the strengths of each partner, the GSP supports
      three global health education programs for public health graduate students and
      surgical residents, including the Tsao Fellowship in Global Health; has initiated
      two international research projects on cleft lip and palate epidemiology; and has
      built upon Operation Smile's service provision. As of January 2015, Tsao fellows
      had operated on over 600 patients during 13 missions in countries including
      China, Vietnam, Mexico, and India. NEXT STEPS: The GSP plans to conduct a formal
      evaluation and then to expand its programs. The GSP encourages other global
      health organizations and academic and medical institutions to engage with each
      other. The partnership described here provides a basic model for structuring
      collaborations in the global health arena.

PMID- 26287916
TI  - AM last page: mastery learning with deliberate practice in medical education.

PMID- 26287917
TI  - Creating a Residency Application Personal Statement Writers Workshop: Fostering
      Narrative, Teamwork, and Insight at a Time of Stress.
AB  - PROBLEM: Every graduating medical student must write a personal statement for the
      Electronic Residency Application Service (ERAS), yet there are no widely
      available resources designed to aid the writing process, causing stress among
      applicants. APPROACH: The authors offered every Medical College of Wisconsin
      senior student in the Classes of 2014 and 2015 a voluntary self-contained two
      hour Residency Application Personal Statement Writers Workshop. The session
      included the selection of writing prompts, speedwriting, and a peer-edit
      critique. Data were gathered before and after each workshop and at the time of
      ERAS submission. OUTCOMES: One hundred nine students elected to participate. Of
      the 96 participants completing a preworkshop questionnaire, only 28 (29%) were
      comfortable with creative and reflective writing. Fifty-four students completed a
      follow-up survey after submitting their ERAS application. Fifty-one (94%) found
      the session effective in getting their personal statement started, and 65 (70%)
      were surprised by the quality of their writing. Almost all could trace some of
      their final statement to the workshop. Forty-six (85%) found working with other
      students helpful, and 49 (91%) would recommend the session to future students; 47
      (87%) agreed that the workshop was "fun." NEXT STEPS: The full workshop will be
      repeated yearly. Workshops will also be offered to residents preparing fellowship
      applications. A shorter version (without the peer-edit critique) was used
      successfully with the entire Class of 2016 to help them reflect on their initial
      clinical encounters. The authors will seek further opportunities to enhance
      reflection for students, residents, and faculty with these techniques.

PMID- 26287918
TI  - The Variables That Lead to Severe Action Decisions by the Liaison Committee on
      Medical Education.
AB  - PURPOSE: To identify the variables associated with severe action decisions (SADs)
      (unspecified accreditation term, warning status, probation status) by the Liaison
      Committee on Medical Education (LCME) regarding the accreditation status of
      established MD-granting medical education programs in the United States and
      Canada. METHOD: The authors reviewed all LCME decisions made on full survey
      reports between October 2004 and June 2012 to test whether SADs were associated
      with an insufficient response in the data collection instrument/self-study,
      chronic noncompliance with one or more accreditation standards, noncompliance
      with specific standards, and noncompliance with a large number of standards.
      RESULTS: The LCME issued 103 nonsevere action decisions and 40 SADs. SADs were
      significantly associated with an insufficient response in the data collection
      instrument/self-study (odds ratio [OR] = 7.30; 95% confidence interval [CI] =
      2.38-22.46); chronic noncompliance with one or more standards (OR = 12.18; 95% CI
      = 1.91-77.55); noncompliance with standards related to the educational program
      for the MD degree (ED): ED-8 (OR = 6.73; 95% CI = 2.32-19.47) and ED-33 (OR =
      5.40; 95% CI = 1.98-14.76); and noncompliance with a large number of standards
      (rpb = 0.62; P < .001). CONCLUSIONS: These findings provide insight into the
      LCME's pattern of decision making. Noncompliance with two standards was strongly
      associated with SADs: lack of evidence of comparability across instructional
      sites (ED-8) and the absence of strong central management of the curriculum (ED
      33). These results can help medical school staff as they prepare for an LCME full
      survey visit.

PMID- 26287919
TI  - Making the case for mastery learning assessments: key issues in validation and
      justification.
AB  - Theoretical and empirical support is increasing for mastery learning, in which
      learners must demonstrate a minimum level of proficiency before completing a
      given educational unit. Mastery learning approaches aim for uniform achievement
      of key objectives by allowing learning time to vary and as such are a course
      level analogue to broader competency-based curricular strategies. Sound
      assessment is the cornerstone of mastery learning systems, yet the nature of
      assessment validity and justification for mastery learning differs in important
      ways from standard assessment models. Specific validity issues include (1) the
      need for careful definition of what is meant by "mastery" in terms of learners'
      achievement or readiness to proceed, the expected retention of mastery over time,
      and the completeness of content mastery required in a particular unit; (2)
      validity threats associated with increased retesting; (3) the need for
      reliability estimates that account for the specific measurement error at the
      mastery versus nonmastery cut score; and (4) changes in item- and test-level
      score variance over retesting, which complicate the analysis of evidence related
      to reliability, internal structure, and relationships to other variables. The
      positive and negative consequences for learners, educational systems, and
      patients resulting from the use of mastery learning assessments must be explored
      to determine whether a given mastery assessment and pass/fail cut score are valid
      and justified. In this article, the authors outline key considerations for the
      validation and justification of mastery learning assessments, with the goal of
      supporting insightful research and sound practice as the mastery model becomes
      more widespread. 

PMID- 26287920
TI  - Building the Infrastructure for Value at UCLA: Engaging Clinicians and Developing
      Patient-Centric Measurement.
AB  - PROBLEM: Evolving payer and patient expectations have challenged academic health
      centers (AHCs) to improve the value of clinical care. Traditional quality
      approaches may be unable to meet this challenge. APPROACH: One AHC, UCLA Health,
      has implemented a systematic approach to delivery system redesign that emphasizes
      clinician engagement, a patient-centric scope, and condition-specific, clinician
      guided measurement. A physician champion serves as quality officer (QO) for each
      clinical department/division. Each QO, with support from a central measurement
      team, has developed customized analytics that use clinical data to define
      targeted populations and measure care across the full treatment episode.
      OUTCOMES: From October 2012 through June 2015, the approach developed rapidly.
      Forty-three QOs are actively redesigning care delivery protocols within their
      specialties, and 95% of the departments/divisions have received a customized
      measure report for at least one patient population. As an example of how these
      analytics promote systematic redesign, the authors discuss how Department of
      Urology physicians have used these new measures, first, to better understand the
      relationship between clinical practice and outcomes for patients with benign
      prostatic hyperplasia and, then, to work toward reducing unwarranted variation.
      Physicians have received these efforts positively. Early outcome data are
      encouraging. NEXT STEPS: This infrastructure of engaged physicians and targeted
      measurement is being used to implement systematic care redesign that reliably
      achieves outcomes that are meaningful to patients and clinicians-incorporating
      both clinical and cost considerations. QOs are using an approach, for multiple
      newly launched projects, to identify, test, and implement value-oriented
      interventions tailored to specific patient populations.

PMID- 26287921
TI  - Correction: Seneca Valley Virus 3Cpro Substrate Optimization Yields Efficient
      Substrates for use in Peptide-Prodrug Therapy.

PMID- 26287922
TI  - Direct-acting antiviral drugs and hepatitis C virus: A therapeutic revolution?

PMID- 26287923
TI  - Diabetes Prevention and Management: What Does a Serious Game Have to Do with It?

PMID- 26287924
TI  - User Assessment of "InsuOnLine," a Game to Fight Clinical Inertia in Diabetes: A
      Pilot Study.
AB  - OBJECTIVE: We performed a pilot study to assess usability and playability of
      "InsuOnLine," a serious game for education of primary care physicians on insulin
      therapy for diabetes mellitus. MATERIALS AND METHODS: A multidisciplinary team
      has designed and developed "InsuOnLine," using Andragogy and Problem-Based
      Learning principles, with game elements to improve players' motivation. The
      prototype was tested by four medical doctors and two medical students, using the
      System Usability Scale (SUS) and a questionnaire to assess playability. These
      results were used to guide corrections, after which the beta version was retested
      by 14 medical students and 6 residents. RESULTS: Out of a maximum score of 100 on
      the SUS, the "InsuOnLine" prototype was rated 88, and some areas for improvement
      were identified (game instructions, controls). After corrections, the beta
      version was rated 92.5 on the SUS. Users have found the beta version to be fun,
      engaging, challenging, relevant, and realistic. Users said that the game has
      increased their knowledge on diabetes and insulin, that it has made them feel
      more confident for prescribing insulin, and that it would have impact on how they
      treated patients with diabetes. Most users said they have learned more from the
      game than they would have from a lecture. Lessons learned were the need of early
      piloting, preferably by users with very little or very much gaming experience, on
      their own computers and free patterns of use. CONCLUSIONS: "InsuOnLine" was rated
      by users as easy to play, fun, and useful for learning. Further studies will
      assess its educational effectiveness. "InsuOnLine" is a promising tool for large
      scale continuing medical education on insulin, helping to fight clinical inertia
      in diabetes.

PMID- 26287925
TI  - Preventing Adolescents' Diabesity: Design, Development, and First Evaluation of
      "Gustavo in Gnam's Planet".
AB  - OBJECTIVE: The goal of this study was to design, develop, and evaluate a game for
      health, "Gustavo in Gnam's Planet" ("Gustavo"), aimed to improve knowledge on
      healthy foods and to increase consumption of healthy foods. SUBJECTS AND METHODS:
      Eighty-three high school students were enrolled in the study. The game was
      designed and developed by a multidisciplinary team. Behavioral change theories
      were adopted to guide the design of the health messages. Participants were
      assessed about food frequency, healthy food knowledge, and the game's interest.
      RESULTS: Forty-seven subjects (mean age, 14.9+/-1.0 years; 72.3 percent males)
      completed the study. At posttest, participants showed significant higher scores
      (i.e., increased knowledge) in the questionnaire on knowledge of healthy foods
      (70.0+/-9.2 versus 71.3+/-10.0 for pretest and posttest, respectively; P<0.05).
      Improvements in healthy eating habits were also detected: higher frequency of
      consumption during a week of white meat (1 [1-2] versus 2 [1-2]; P=0.01), eggs (1
      [1-1] versus 1 [1-2]; P=0.01], and legumes (1 [0-1] versus 1 [1-2]; P=0.03) and
      lower frequency of consumption of sugar-containing packaged snacks (1 [0-1]
      versus 0 [0-1]; P=0.009). Most of the participants found the game easy to use and
      clear in its content. Half of the participants found the game interesting.
      CONCLUSIONS: Our study shows that "Gustavo" is a promising tool for health
      education, in schools or in other environments. Limitations of the study and
      future directions are discussed.

PMID- 26287926
TI  - The Use of Videogames, Gamification, and Virtual Environments in the Self
      Management of Diabetes: A Systematic Review of Evidence.
AB  - The use of videogames in healthcare interventions is gaining popularity, but
      there is still a gap in the understanding on how these types of interventions are
      used for the management of diabetes. The purpose of this review is to examine
      published research on the use of videogames for diabetes management. With the
      increased use of mobile technology, the review was expanded to understand whether
      games, gamification, and virtual environments can be used for diabetes self
      management. Out of the 307 articles identified, only 10 articles met the
      inclusion criteria of the study. The duration of most studies was short, with
      small sample sizes. All interventions targeted behavioral changes examining risk
      reduction of diabetes-related risk and promotion of healthy behavior among study
      participants. Videogames appeared to be helpful tools for education in some
      interventions, whereas gamification and virtual environments increased extrinsic
      motivation and provided positive reinforcement. This review concludes by
      discussing the potential of using videogames and gamification for the self
      management of diabetes. 

PMID- 26287928
TI  - Association Between Extraversion and Exercise Performance Among Elderly Persons
      Receiving a Videogame Intervention.
AB  - OBJECTIVE: We examined the effects of an exergame intervention on exercise
      performance, as well as the influence of players' personality traits on the
      effects of the intervention. MATERIALS AND METHODS: In total, 16 elderly persons
      (>65 years old) participated in the study for 12 weeks. Participants were
      required to complete the Big Five Scale. We measured the number of times that the
      sit-to-stand exercise was performed during the interventions with and without
      exergames. RESULTS: We compared the average number of times that the sit-to-stand
      exercise was performed per day in each of the two conditions. The average number
      of times that exercise was undertaken with exergame use was greater than that
      without exergame use; however, no significant difference was found. The
      difference between the average number of times that exercise occurred with and
      without exergame use was positively correlated with neuroticism, negatively
      correlated with extraversion, and not associated with conscientiousness.
      CONCLUSIONS: The intervention comprising the use of exergames has a positive
      motivational influence among less extraverted elderly persons.

PMID- 26287929
TI  - Mapping the Demand for Serious Games in Postgraduate Medical Education Using the
      Entrustable Professional Activities Framework.
AB  - OBJECTIVE: Serious games are potentially powerful tools for residency training
      and increasingly attract attention from medical educators. At present, serious
      games have little evidence-based relations with competency-based medical
      education, which may impede their incorporation into residency training programs.
      The aim of this study was to identify highly valued entrustable professional
      activities (EPAs) to support designers in the development of new, serious games
      built on a valid needs-assessment. MATERIALS AND METHODS: All 149 licensed
      medical specialists from seven specialties in one academic hospital participated
      in seven different Delphi expert panels. They filled out a two-round Delphi
      survey, aimed at identifying the most valuable EPAs in their respective
      curricula. Specialists were asked to name the most highly valued EPA in their
      area in the first Delphi round. In the second round, the generated responses were
      presented and ranked according to priority by the medical specialists. RESULTS:
      Sixty-two EPAs were identified as valuable training subjects throughout five
      specialties. Eleven EPAs--"management of trauma patient," "chest tube placement,"
      "laparoscopic cholecystectomy," "assessment of vital signs," "airway management,"
      "induction of general anesthesia," "assessment of suicidal patient," "psychiatric
      assessment," "gastroscopy," "colonoscopy," and "resuscitation of emergency
      patients"--were consistently given a high score. CONCLUSIONS: The future medical
      specialist is an active learner, comfortable with digital techniques and learning
      strategies such as serious gaming. In order to maximize the impact and acceptance
      of new serious games, it is vital to select the most relevant training subjects.
      Although some serious games have already targeted top-priority EPAs, plenty of
      opportunities remain.

PMID- 26287927
TI  - Clinical and Neurobiological Perspectives of Empowering Pediatric Cancer Patients
      Using Videogames.
AB  - Pediatric oncology patients often experience fatigue and physical and mental
      deconditioning during and following chemotherapy treatments, contributing to
      diminished quality of life. Patient empowerment is a core principle of patient
      centered care and reflects one's ability to positively affect his or her own
      health behavior and health status. Empowerment interventions may enhance
      patients' internal locus of control, resilience, coping skills, and self
      management of symptoms related to disease and therapy. Clinical and technological
      advancements in therapeutic videogames and mobile medical applications (mobile
      health) can facilitate delivery of the empowerment interventions for medical
      purposes. This review summarizes clinical strategies for empowering pediatric
      cancer patients, as well as their relationship with developing a "fighting
      spirit" in physical and mental health. To better understand physiological aspects
      of empowerment and to elucidate videogame-based intervention strategies, brain
      neuronal circuits and neurotransmitters during stress, fear, and resilience are
      also discussed. Neuroimaging studies point to the role of the reward system
      pathways in resilience and empowerment in patients. Taken together, videogames
      and mobile health applications open translational research opportunities to
      develop and deliver empowerment interventions to pediatric cancer patients and
      also to those with other chronic diseases. 

PMID- 26287930
TI  - A Pilot Study Evaluating "Dojo," a Videogame Intervention for Youths with
      Externalizing and Anxiety Problems.
AB  - OBJECTIVE: Externalizing problems, which are the main reason for youth referrals
      to mental health agencies, are highly persistent and predict a range of negative
      outcomes. Youths with externalizing problems are also frequently comorbid with
      anxiety. Among the most widely recognized evidence-based treatments is cognitive
      behavioral therapy (CBT). Although CBT principles seem to be sound, effect sizes
      remain moderate, suggesting improvements could be made to this conventional
      treatment approach. The main premise of the current pilot study is to investigate
      the feasibility of implementing a videogame intervention ("Dojo" [Gamedesk, Los
      Angeles, CA]) that incorporates CBT principles and aims to address the
      limitations of conventional CBT delivery models, with the ultimate goal of
      improving outcomes for this difficult-to-treat population. MATERIALS AND METHODS:
      "Dojo" is an emotion management game that helps youths to recognize and control
      their physiological and emotional arousal. We explored the implementation and
      user experience of "Dojo" in a sample of eight adolescents in residential
      treatment for both externalizing and anxiety problems. RESULTS: Participants
      attended all sessions without complaints. They evaluated "Dojo" very positively
      and exhibited high compliance during the training sessions. We encountered some
      problems with session scheduling and obtaining mentor reports. Quantitative data
      show the predicted decrease in three out of four measurements. CONCLUSIONS: The
      smooth implementation, high user satisfaction, high self-reported compliance
      during training sessions, and initial outcome results all indicate the high
      potential "Dojo" holds as an innovative intervention. If additional rigorously
      designed randomized controlled trials prove to be successful, "Dojo" can be a
      cost-effective way to engage high-risk youths in effective intervention.

PMID- 26287931
TI  - Examining the Feasibility of Smartphone Game Applications for Physical Activity
      Promotion in Middle School Students.
AB  - OBJECTIVE: The objective of this study was to determine the feasibility (i.e.,
      limited efficacy testing, practicality, and acceptability) of a 6-week smartphone
      game-based applications program for promoting physical activity (PA) in
      adolescents in an afterschool program. MATERIALS AND METHODS: This mixed-method,
      quasi-experimental design study included 27 adolescents who evaluated four
      smartphone PA game-based applications in two Boys & Girls Clubs of America. After
      an initial baseline week (i.e., usual activity during their visit to the Club),
      adolescents played each game for 1 week. During a final week, the participants
      could choose to play any combination of the four games. An established conceptual
      framework was used to assess feasibility. Efficacy was assessed by changes in PA
      via wrist-worn accelerometers (model GT3x+; ActiGraph LLC, Pensacola, FL).
      Practicality was measured through field notes, the number of players attending
      each session, and the proportion of attendees who played the games. Acceptability
      was measured using poststudy focus groups. RESULTS: Compared with baseline (3.22
      metabolic equivalents [METs]), mean accelerometer values were significantly
      (P<0.05) higher during "Space Rayders" (4.33 METs) and "Color Hunt" (3.67 METs).
      Attendance did not differ among games, and weekly number of players averaged 12
      of 27 participants. Qualitative findings indicated that participants perceived
      "Space Rayders" as the most acceptable game. Overall, participants found the
      games to be enjoyable and easy to use, although they had suggestions to improve
      graphics and sounds. CONCLUSIONS: Smartphone games can be feasible for
      adolescents to use for PA. Lessons learned will be used to provide improvements
      for future game development and evaluation.

PMID- 26287932
TI  - Protective properties of ginsenoside Rb3 against UV-B radiation-induced oxidative
      stress in HaCaT keratinocytes.
AB  - This work aimed to evaluate the skin anti-photoaging properties of ginsenoside
      Rb3 (Rb3), one of the main protopanaxdiol-type ginsenosides from ginseng, in
      HaCaT keratinocytes. The skin anti-photoaging activity was assessed by analyzing
      the levels of reactive oxygen species (ROS), pro-matrix metalloproteinase-2
      (proMMP-2), pro-matrix metalloproteinase-9 (proMMP-9), total glutathione (GSH),
      and superoxide dismutase (SOD) activity as well as cell viability in HaCaT
      keratinocytes under UV-B irradiation. When HaCaT keratinocytes were exposed to
      Rb3 prior to UV-B irradiation, Rb3 exhibited suppressive activities on UV-B
      induced ROS, proMMP-2, and proMMP-9 enhancements. On the contrary, Rb3 displayed
      enhancing activities on UV-B-reduced total GSH and SOD activity levels. Rb3 could
      not interfere with cell viabilities in UV-B-irradiated HaCaT keratinocytes. Rb3
      plays a protective role against UV-B-induced oxidative stress in human HaCaT
      keratinocytes, proposing its potential skin anti-photoaging properties.

PMID- 26287933
TI  - Layered bismuth oxyhalide nanomaterials for highly efficient tumor photodynamic
      therapy.
AB  - Layered bismuth oxyhalide nanomaterials have received much more interest as
      promising photocatalysts because of their unique layered structures and high
      photocatalytic performance, which can be used as potential inorganic
      photosensitizers in tumor photodynamic therapy (PDT). In recent years,
      photocatalytic materials have been widely used in PDT and photothermal therapy
      (PTT) as inorganic photosensitizers. This investigation focuses on applying
      layered bismuth oxyhalide nanomaterials toward cancer PDT, an application that
      has never been reported so far. The results of our study indicate that the
      efficiency of UV-triggered PDT was highest when using BiOCl nanoplates followed
      by BiOCl nanosheets, and then TiO2. Of particular interest is the fact that
      layered BiOCl nanomaterials showed excellent PDT effects under low nanomaterial
      dose (20 MUg mL(-1)) and low UV dose (2.2 mW cm(-2) for 10 min) conditions, while
      TiO2 showed almost no therapeutic effect under the same parameters. BiOCl
      nanoplates and nanosheets have shown excellent performance and an extensive range
      of applications in PDT. 

PMID- 26287934
TI  - Protective effects of probiotic Lactobacillus plantarum BJ0021 on liver and
      kidney oxidative stress and apoptosis induced by endosulfan in pregnant rats.
AB  - Endosulfan (EDS) is one of the most widely organochlorine insecticide used in
      many parts of the world, although it is currently banned or severely restricted
      in use in some countries. EDS causes a variety of negative effects in non-target
      species including humans. Therefore, the aim of the present study was to
      investigate the possible protective effects of Lactobacillus plantarum BJ0021 on
      toxicity, oxidative stress, and apoptosis induced by EDS intoxication on liver
      and kidneys of pregnant rats. This pesticide induced a significant increase in
      total cholesterol, alanine-amino transferase (ALAT), aspartate-amino transferase
      (ASAT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), urea and
      creatinine in serum, while urinary urea and creatinine were lower than those of
      the control group. In the liver and kidney, lipid peroxidation increased
      significantly, the antioxidant levels, such as superoxide dismutase (SOD) and
      catalase (CAT) were markedly depressed and TdT-mediated dUTP-biotin Nick End
      Labeling (TUNEL) revealed more apoptotic cells. In contrast, co-administration of
      L. plantarum BJ0021 to EDS-treated animals ameliorated most of these biochemical
      parameters, but the activity of antioxidant enzymes (SOD, CAT) did not modify and
      the number of apoptotic nuclei remained significantly raised in kidney compared
      to control. In conclusion, the administration of L. plantarum BJ0021 decreased
      apoptosis and might play a protective role in reducing toxicity of EDS in
      pregnant rats. 

PMID- 26287935
TI  - Sensory eye balance in surgically corrected intermittent exotropes with normal
      stereopsis.
AB  - Surgery to align a deviated or strabismic eye is often done for both functional
      as well as cosmetic reasons. Although amblyopia is often an impediment to
      regaining full binocularity in strabismics in general, intermittent exotropes,
      because their deviation is intermittent, have no amblyopia and some degree of
      stereopsis. Binocular function, including a balanced ocular dominance, could be
      expected to be normal after surgical correction if normal levels of stereopsis
      and visual acuity are postsurgically achieved. Here we used a binocular phase
      combination paradigm to quantitatively assess the ocular dominance in a group of
      surgically corrected intermittent exotropes who have normal stereo and visual
      acuity as defined clinically. Interestingly, we found significant interocular
      imbalance (balance point < 0.9) in most of the surgically treated patients (8 out
      10) but in none of the controls. We conclude that the two eyes may still have a
      residual sensory imbalance in surgically corrected strabismus even if stereopsis
      is within normal limits. Our study opens the possibility that a further treatment
      aimed at re-balancing the ocular dominance might be necessary in surgically
      treated intermittent exotropia to provide more efficient binocular processing in
      the long term. 

PMID- 26287936
TI  - SOX10 and Olig2 as negative markers for the diagnosis of ependymomas: An
      immunohistochemical study of 98 glial tumors.
AB  - SOX10 belongs to the family of transcription factors essential for the
      development of neural crest, peripheral nervous system and melanocytes. It is
      presently used in histopathology as a marker of melanocytic differentiation.
      SOX10 is expressed in normal brain tissue in oligodendrocytes, but the
      information about SOX10 expression in primary tumors of the central nervous
      system is quite limited. In this study, we examined the expression of SOX10 and
      Olig2 by immunohistochemistry in a series of 98 glial tumors and explored their
      specificity and sensitivity for differential diagnosis of ependymal vs non
      ependymal tumors. In addition, we examined the expression of EMA and CD99 in
      ependymal tumors. SOX10 and Olig2 staining were scored as negative if no positive
      cells or only a few positive cells (typically up to 1-3%) were found. In all
      other instances, SOX10 or Olig2 staining was scored as positive. Out of 44
      examined ependymal tumors none was found to express SOX10 and 7 specimens showed
      only a few SOX10-positive cells that likely corresponded to entrapped non
      neoplastic oligodendrocytes. In contrast, non-ependymal tumors expressed SOX10 in
      26/54 (48%) specimens. Olig2 was positive in 5 out of 44 ependymomas (11%) and 50
      out of 54 (93%) non-ependymal tumors (astrocytomas and oligodendrogliomas). EMA
      and CD99 expression was found in 33/44 (75%) and 11/44 (25%) of ependymomas,
      respectively. SOX10-positivity rules out the diagnosis of ependymoma among other
      glial tumors with high confidence. 

PMID- 26287937
TI  - A Coupled Lumped-Parameter and Distributed Network Model for Cerebral Pulse-Wave
      Hemodynamics.
AB  - The cerebral circulation is unique in its ability to maintain blood flow to the
      brain under widely varying physiologic conditions. Incorporating this
      autoregulatory response is necessary for cerebral blood flow (CBF) modeling, as
      well as investigations into pathological conditions. We discuss a one-dimensional
      (1D) nonlinear model of blood flow in the cerebral arteries coupled to
      autoregulatory lumped-parameter (LP) networks. The LP networks incorporate
      intracranial pressure (ICP), cerebrospinal fluid (CSF), and cortical collateral
      blood flow models. The overall model is used to evaluate changes in CBF due to
      occlusions in the middle cerebral artery (MCA) and common carotid artery (CCA).
      Velocity waveforms at the CCA and internal carotid artery (ICA) were examined
      prior and post MCA occlusion. Evident waveform changes due to the occlusion were
      observed, providing insight into cerebral vasospasm monitoring by morphological
      changes of the velocity or pressure waveforms. The role of modeling of collateral
      blood flows through cortical pathways and communicating arteries was also
      studied. When the MCA was occluded, the cortical collateral flow had an important
      compensatory role, whereas the communicating arteries in the circle of Willis
      (CoW) became more important when the CCA was occluded. To validate the model,
      simulations were conducted to reproduce a clinical test to assess dynamic
      autoregulatory function, and results demonstrated agreement with published
      measurements. 

PMID- 26287938
TI  - Extracellular vesicle microRNAs: biomarker discovery in various diseases based on
      RT-qPCR.
AB  - In recent years, biomarker discovery based on extracellular microRNAs (miRNAs),
      especially exosome miRNAs, has drawn wide attention. While exosome isolation and
      identification technologies are increasingly sophisticated, the preanalytical
      process of exosome miRNAs seems to be no longer a crucial problem. Though next
      generation sequencing, microarray and digital PCR have been recommended as good
      downstream analytical platforms for exosome miRNA quantification, they are still
      more constrained in clinical utility compared with RT-qPCR method at present. In
      this review, we will trace back to the origin and summarize current studies of
      biomarker discovery based on extracellular vesicle miRNAs, and provide an
      overview and latest developments of RT-qPCR-based data normalization, in order to
      further assist the development of translational medicine. 

PMID- 26287939
TI  - Effect of genotype and methylation of CYP2D6 on smoking behaviour.
AB  - OBJECTIVE: Cigarette smoking is one of the most influential environmental factors
      affecting the DNA methylation patterns. The addiction-causing substance of
      tobacco smoke, nicotine, has also shown the potential to alter DNA methylation
      patterns. However, genetics has a strong influence on DNA methylation patterns,
      which in turn may affect an individual's smoking behaviour. MATERIALS AND
      METHODS: We studied eight functional gene variants of one of the most important
      drug-metabolizing enzymes, CYP2D6, in relation to smoking behaviour in our well
      characterized study population consisting of 1230 Whites of Russian origin. In
      addition, potential associations between methylation levels in a CpG island in
      the CYP2D6 gene and sex, age, different smoking-related phenotypes and CYP2D6
      genotypes were studied. RESULTS: Both age and sex were found to be associated
      with the methylation level of the CYP2D6 gene. The CYP2D6 methylation pattern
      also showed high genotype dependence; compared with the extensive metabolizer
      genotype, the poor metabolizer genotype occurred notably more frequently with
      higher methylation status (odds ratio 5.05, 95% confidence interval 2.14-11.90).
      Moreover, higher methylation levels were found to be related inversely to heavier
      smoking (odds ratio 0.56, 95% confidence interval 0.35-0.91). We also found
      associations between the CYP2D6 genotype and smoking habits; the poor metabolizer
      genotype tended to decrease the risk of becoming a heavy smoker compared with the
      extensive metabolizers, whereas the ultrarapid metabolism-related genotypes
      tended to increase the risk. CONCLUSION: The CYP2D6-related metabolic capacity
      seems to be related to cigarette consumption both through genetic and through
      epigenetic mechanisms.

PMID- 26287940
TI  - Genetic variations in the mTOR gene contribute toward gastric adenocarcinoma
      susceptibility in an Eastern Chinese population.
AB  - BACKGROUND AND AIM: Genetic variants in the mammalian target of rapamycin (mTOR)
      gene have become an interesting topic for the study of genetic susceptibility to
      cancer, but their associations with the risk of gastric cancer have not been
      fully investigated. MATERIALS AND METHODS: In a hospital-based case-control study
      of 1002 gastric cancer patients and 1003 cancer-free controls, we genotyped four
      potentially functional single nucleotide polymorphisms (SNPs) (rs1034528G>C,
      rs17036508T>C, rs3806317A>G, and rs2295080T>G) of mTOR and assessed their
      associations with the risk of gastric cancer using univariate and multivariate
      logistic regression analyses. We also used the multifactorial dimension reduction
      analysis to explore possible interactions and the false-positive report
      probabilities to assess significant findings. RESULTS: We found that rs1034528
      CG/CC and rs3806317 GA/GG variant genotypes were associated with an increased
      risk of gastric cancer under a dominant model (adjusted odds ratio=1.27 and 1.22,
      respectively). In the combined analysis of all four SNPs under investigation,
      patients with 3-4 risk genotypes of mTOR had a significantly increased risk of
      gastric cancer (adjusted odds ratio=1.46, 95% confidence interval=1.19-1.79)
      compared with those with 0-2 risk genotypes. Stratified analysis indicated that
      this risk was more pronounced in subgroups of men, never-smokers, never-drinkers,
      and clinical stages III+IV. The multifactorial dimension reduction analysis
      suggested some evidence of interactions between the combined genotypes and other
      risk factors for gastric cancer. CONCLUSION: These findings suggest that
      potentially functional SNPs of mTOR may individually or collectively contribute
      to the risk of gastric cancer. Larger studies with diverse ethnic populations are
      warranted to validate our findings.

PMID- 26287941
TI  - Polymorphisms associated with renal adverse effects of antiretroviral therapy in
      a Southern Brazilian HIV cohort.
AB  - OBJECTIVE: This study evaluated the impact of seven single nucleotide
      polymorphisms in five candidate genes (ABCB1, ABCC2, ABCC4, SLC22A6, and
      SLC22A11) in relation to nephrotoxicity associated with highly active
      antiretroviral therapy (HAART) in HIV-infected individuals. METHODS: The
      following single nucleotide polymorphisms were genotyped by real-time PCR: ABCB1
      rs1045642, ABCC2 rs717620 and rs2273697, ABCC4 rs1751034 and rs3742106, SLC22A6
      rs11568626, and SLC22A11 rs11231809 in 507 HIV-infected patients from the city of
      Porto Alegre, Southern Brazil, receiving HAART for, at least, 1 year. RESULTS:
      From the 507 HIV-infected patients recruited, 19.1% presented a reduction in
      estimated glomerular filtration rate (eGFR). A total of 16 (3.2%) patients
      fulfilled the criteria for chronic kidney disease (defined as eGFR<60 ml/min/1.73
      m). Individuals carrying at least one T allele of ABCC2 -24 C>T (rs717620)
      presented lower eGFR than C/C homozygotes (104 +/- 22 vs. 108 +/- 22 ml/min/1.73
      m, independent-samples t-test, P=0.040). In multivariate analysis, the predictors
      associated with decreased eGFR were time of treatment, tenofovir use,
      atazanavir/ritonavir use, and carrying one T allele of ABCC2 -24 C>T. CONCLUSION:
      Our data support the importance of genetic factors in the etiology of
      nephrotoxicity in patients treated with HAART. Studies to verify treatment
      implications of genotyping before HAART initiation may be advisable to guide the
      selection of an appropriate antiretroviral therapy regimen.

PMID- 26287942
TI  - Benefits of completing pulmonary rehabilitation in patients with asthma.
AB  - BACKGROUND: Asthma affects 30 million Americans and results in reduced
      productivity and quality of life. Pulmonary rehabilitation (PR) is known to
      improve physical conditioning and exercise performance in chronic lung diseases
      such as COPD, however, few studies have examined its benefits in patients with
      asthma. We aimed to determine the benefits of PR in this population as well as
      the predictors of completion of therapy. METHODS: We performed a retrospective
      review of data from patients with a diagnosis of asthma who participated in PR at
      our institution from 1996 to 2013. Nine hundred and nineteen patients
      participated in the program of whom 75 were referred with a primary diagnosis of
      asthma. Patients underwent physiologic testing and their symptoms and quality of
      life were assessed using validated questionnaires. For patients who completed PR
      (n = 37), data obtained at the initial and exit visit was compared.
      Characteristics of completers were compared to non-completers to determine
      predictors of successful completion. RESULTS: Individuals with asthma completing
      PR had improvement from baseline to exit visit in Six Minute Walk Distance (326
      vs. 390 feet; p < 0.0001), decreased body mass index (33 vs. 32 kg/m2; p <
      0.046), decreased Beck Depression Inventory scores (15 vs. 9; p < 0.0009), and
      increased Short Form-36 scores (345 vs. 445; p = 0.0005). In a multivariate
      logistic regression analysis, lower depression scores predicted completion (OR
      1.08, 95% CI 1.02-1.15, p = 0.02). CONCLUSION: Patients with asthma who completed
      PR had improvement in physical function and emotional well-being. Depression is a
      risk factor for non-completion of PR. Further research is needed to determine
      which patients will benefit most from therapy.

PMID- 26287943
TI  - Simulated Solvation of Organic Ions II: Study of Linear Alkylated Carboxylate
      Ions in Water Nanodrops and in Liquid Water. Propensity for Air/Water Interface
      and Convergence to Bulk Solvation Properties.
AB  - We investigated the solvation of carboxylate ions from formate to hexanoate, in
      droplets of 50 to 1000 water molecules and neat water, by computations using
      standard molecular dynamics and sophisticated polarizable models. The carboxylate
      ions from methanoate to hexanoate show strong propensity for the air/water
      interface in small droplets. Only the ions larger than propanoate retain
      propensity for the interface in larger droplets, where their enthalpic
      stabilization by ion/water dispersion is reduced there by 3 kcal mol(-1) per CH2
      group. This is compensated by entropy effects over +3.3 cal mol(-1) K(-1) per CH2
      group. On the surface, the anionic headgroups are strongly oriented toward the
      aqueous core, while the hydrophobic alkyl chains are repelled into air and lose
      their structure-making effects. These results reproduce the structure-making
      effects of alkyl groups in solution, and suggest that the hydrocarbon chains of
      ionic headgroups and alkyl substituents solvate independently. Extrapolation to
      bulk solution using standard extrapolation schemes yields absolute carboxylate
      solvation energies. The results for formate and acetate yield a proton solvation
      enthalpy of about 270 kcal mol(-1), close to the experiment-based value. The
      largest carboxylate ions yield a value smaller by about 10 kcal mol(-1), which
      requires studies in much larger droplets. 

PMID- 26287944
TI  - Structural Transformation of 8-5-Coupled Dehydrodiferulates by Human Intestinal
      Microbiota.
AB  - Ingested dehydrodiferulates (DFAs) are partially released from cereal dietary
      fiber by human colonic microbiota, but little research has explored the further
      microbial metabolism of 8-5-coupled DFAs. This study investigated the in vitro
      microbial metabolism and elucidated major metabolites of free 8-5-DFAs
      (benzofuran and open forms) and an esterified analogue, 8-5-DFA diethyl ester
      (benzofuran). Synthesized standard compounds were incubated with fresh human
      fecal suspensions. Metabolites were isolated and structurally elucidated using
      high-resolution-LC-time-of-flight-(ToF)-MS, GC-MS, and NMR. Nine metabolite
      structures were unambiguously characterized with NMR, and four additional
      metabolites were tentatively identified to reveal structural conversion motifs:
      propenyl side chain hydrogenation (all substrates), O-demethylation and reductive
      ring-opening (8-5-DFA diethyl ester and free 8-5-DFA [benzofuran]), and de
      esterification (8-5-DFA diethyl ester). A pathway of microbial 8-5-DFA metabolism
      was proposed based on metabolite formation kinetics. Importantly, de
      esterification of the 8-5-DFA diethyl ester occurred primarily after and/or
      concurrently with other metabolism steps. Cleavage to monomers was not observed. 

PMID- 26287945
TI  - Medical terminology in online patient-patient communication: evidence of high
      health literacy?
AB  - BACKGROUND: Health communication research and guidelines often recommend that
      medical terminology be avoided when communicating with patients due to their
      limited understanding of medical terms. However, growing numbers of e-patients
      use the Internet to equip themselves with specialized biomedical knowledge that
      is couched in medical terms, which they then share on participatory media, such
      as online patient forums. OBJECTIVE: Given possible discrepancies between
      preconceptions about the kind of language that patients can understand and the
      terms they may actually know and use, the purpose of this paper was to
      investigate medical terminology used by patients in online patient forums.
      DESIGN: Using data from online patient-patient communication where patients
      communicate with each other without expert moderation or intervention, we coded
      two data samples from two online patient forums dedicated to thyroid issues.
      RESULTS: Previous definitions of medical terms (dichotomized into technical and
      semi-technical) proved too rudimentary to encapsulate the types of medical terms
      the patients used. Therefore, using an inductive approach, we developed an
      analytical framework consisting of five categories of medical terms: dictionary
      defined medical terms, co-text-defined medical terms, medical initialisms,
      medication brand names and colloquial technical terms. The patients in our data
      set used many medical terms from all of these categories. DISCUSSION AND
      CONCLUSIONS: Our findings suggest the value of a situated, condition-specific
      approach to health literacy that recognizes the vertical kind of knowledge that
      patients with chronic diseases may have. We make cautious recommendations for
      clinical practice, arguing for an adaptive approach to medical terminology use
      with patients.

PMID- 26287946
TI  - Definitive radiotherapy plus regional hyperthermia for high-risk and very high
      risk prostate carcinoma: Thermal parameters correlated with biochemical relapse
      free survival.
AB  - PURPOSE: The aim of this study was to assess the efficacy of definitive
      radiotherapy (RT) plus regional hyperthermia (HT) and investigate the potential
      contribution of HT to clinical outcomes in patients with prostate carcinoma.
      MATERIALS AND METHODS: Following our institution's treatment protocol, HT was
      combined with RT to improve clinical outcomes in selected patients with high-risk
      or very high-risk prostate cancer. Data from 82 patients treated with RT plus HT
      and 64 patients treated with RT alone were retrospectively analysed. RESULTS:
      Median follow-up duration was 61 months. The 5-year biochemical disease-free
      survival (bDFS) rate for the 82 patients treated with RT plus HT was 78%, whereas
      bDFS for the 64 patients treated with RT alone was 72%; this difference was not
      significant. Among the 75 patients treated with RT plus HT who underwent intra
      rectal temperature measurements, higher thermal parameters were significant
      prognostic indicators of improved bDFS by univariate analysis. A higher CEM43 
      degrees CT90 thermal parameter and a T stage of T1-2 were significant prognostic
      factors based on multivariate analysis. The 5-year bDFS rates for the 40 patients
      with a higher CEM43  degrees CT90 and the 64 patients treated with RT alone were
      significantly different, whereas 5-year bDFS for the 35 patients with a lower
      CEM43  degrees CT90 and the 64 patients treated with RT alone were not.
      CONCLUSIONS: The addition of HT with higher thermal parameters to RT may improve
      bDFS for patients with high-risk or very high-risk prostate cancer. These
      findings also demonstrate the importance of careful selection of treatable
      patients with higher thermal parameters.

PMID- 26287947
TI  - Cu-Catalyzed Three-Component Cascade Annulation Reaction: An Entry to
      Functionalized Pyridines.
AB  - A concise copper-catalyzed N-O bond cleavage/C-C/C-N bond formation procedure has
      been described for the synthesis of multisubstituted pyridines. Various oxime
      acetates, activated methylene compounds, and a wide range of aldehydes bearing
      aryl, heteroaryl, vinyl, and trifluoromethyl groups were employed to provide the
      tri- or tetrasubstituted pyridines with flexible substitution patterns. Moreover,
      this method features inexpensive catalysts, no need for extra oxidant, and high
      step-enconomy, which make it pratical and attractive. 

PMID- 26287948
TI  - Investigating the Discriminatory Power of BCS-Biowaiver in Vitro Methodology to
      Detect Bioavailability Differences between Immediate Release Products Containing
      a Class I Drug.
AB  - The purpose of this work is to investigate the discriminatory power of the
      Biopharmaceutics Classification System (BCS)-biowaiver in vitro methodology,
      i.e., to investigate if a BCS-biowaiver approach would have detected the Cmax
      differences observed between two zolpidem tablets and to identify the cause of
      the in vivo difference. Several dissolution conditions were tested with three
      zolpidem formulations: the reference (Stilnox), a bioequivalent formulation (BE),
      and a nonbioequivalent formulation (N-BE). Zolpidem is highly soluble at pH 1.2,
      4.5, and 6.8. Its permeability in Caco-2 cells is higher than that of metoprolol
      and its transport mechanism is passive diffusion. None of the excipients (alone
      or in combination) showed any effect on permeability. All formulations dissolved
      more than 85% in 15 min in the paddle apparatus at 50 rpm in all dissolution
      media. However, at 30 rpm the nonbioequivalent formulation exhibited a slower
      dissolution rate. A slower gastric emptying rate was also observed in rats for
      the nonbioequivalent formulation. A slower disintegration and dissolution or a
      delay in gastric emptying might explain the Cmax infra-bioavailability for a
      highly permeable drug with short half-life. The BCS-biowaiver approach would have
      declared bioequivalence, although the in vivo study was not conclusive but
      detected a 14% mean difference in Cmax that precluded the bioequivalence
      demonstration. Nonetheless, these findings suggest that a slower dissolution rate
      is more discriminatory and that rotation speeds higher than 50 rpm should not be
      used in BCS-biowaivers, even if a coning effect occurs. 

PMID- 26287949
TI  - Opportunistic Infections among People Living with HIV (PLHIV) with Diabetes
      Mellitus (DM) Attending a Tertiary Care Hospital in Coastal City of South India.
AB  - BACKGROUND: HIV/AIDS and Diabetes Mellitus are the diseases' known to supress
      cell mediated immunity and predispose patients for opportunistic infections.
      Hence, we conducted a study to compare the common opportunistic infections (OIs)
      between People Living with HIV with DM (PLHIV-DM) and PLHIV without DM (PLHIV).
      METHODOLOGY: PLHIV with DM and without DM (1:1) were prospectively included in
      the study from January 2011 to January 2012 at a tertiary care hospital in
      Mangalore city. Patients were classified as Diabetic if their fasting plasma
      glucose was >= 7.0 mmol/l (126 mg/dl) or 2-h plasma glucose was >=11.1 mmol/l
      (200 mg/dl). Standard procedures and techniques were followed for diagnosis of
      OIs as per WHO guidelines. The data was entered and analyzed using Statistical
      Package for Social Sciences (SPSS) version 11.5. FINDINGS: The study included 37
      PLHIV with DM and 37 PLHIV without DM and both groups were treated with Anti
      Retroviral Therapy (ART). The median age was 47 years (IQR: 41-55 years) for
      PLHIV-DM as compared to 40 years (IQR: 35-45.5 years) for PLHIV (p<0.0001). PLHIV
      DM had median CD4 counts of 245 (IQR: 148-348) cells/MUl compared to 150(IQR: 70
      278) cells/MUl for PLHIV (p = 0.02). Common OIs included oral candidiasis (49% of
      PLHIV-DM and 35% of PLHIV); Cryptococcal meningitis (19% of PLHIV-DM and 16% of
      PLHIV); Pneumocystis jiroveci pneumonia (5% of PLHIV-DM and 18% of PLHIV); extra
      pulmonary tuberculosis (22% of PLHIV-DM and 34.5% of PLHIV); and Cerebral
      toxoplasmosis (11% of PLHIV-DM and 13.5% of PLHIV). Microbiological testing of
      samples from PLHIV-DM, C krusei was the most common Candida species isolated from
      9 out of 18 samples. Out of six pulmonary TB samples cultured, four grew Non
      tuberculosis mycobacteria (NTM) and two Mycobacterium tuberculosis complexes.
      CONCLUSIONS: Study did not identify any significant difference in profile of
      opportunistic infections (OIs) between PLHIV with and without Diabetes.

PMID- 26287950
TI  - Development of multiplex PCR assay for authentication of Cornu Cervi Pantotrichum
      in traditional Chinese medicine based on cytochrome b and C oxidase subunit 1
      genes.
AB  - This study describes a method for discriminating the true Cervus antlers from its
      counterfeits using multiplex PCR. Bioinformatics were carried out to design the
      specific alleles primers for mitochondrial (mt) cytochrome b (Cyt b) and
      cytochrome C oxidase subunit 1 (Cox 1) genes. The mt DNA and genomic DNA were
      extracted from Cervi Cornu Pantotrichum through the modified alkaline and the
      salt-extracting method in addition to its counterfeits, respectively. Sufficient
      DNA templates were extracted from all samples used in two methods, and joint
      fragments of 354 bp and 543 bp that were specifically amplified from both of true
      Cervus antlers served as a standard control. The data revealed that the multiplex
      PCR-based assays using two primer sets can be used for forensic and quantitative
      identification of original Cervus deer products from counterfeit antlers in a
      single step.

PMID- 26287952
TI  - Capillary rupture of suspended polymer concentric rings.
AB  - We present the first experimental study on the simultaneous capillary instability
      amongst viscous concentric rings suspended atop an immiscible medium. The rings
      ruptured upon annealing, with three types of phase correlation between
      neighboring rings. In the case of weak substrate confinement, the rings ruptured
      independently when they were sparsely distanced, but via an out-of-phase mode
      when packed closer. If the substrate confinement was strong, the rings would
      rupture via an in-phase mode, resulting in radially aligned droplets. The
      concentric ring geometry caused a competition between the phase correlation of
      neighboring rings and the kinetically favorable wavelength, yielding an
      intriguing, recursive surface pattern. This frustrated pattern formation behavior
      was accounted for by a scaling analysis. 

PMID- 26287951
TI  - The Effect of Digestive Capacity on the Intake Rate of Toxic and Non-Toxic Prey
      in an Ecological Context.
AB  - Digestive capacity often limits food intake rate in animals. Many species can
      flexibly adjust digestive organ mass, enabling them to increase intake rate in
      times of increased energy requirement and/or scarcity of high-quality prey.
      However, some prey species are defended by secondary compounds, thereby forcing a
      toxin limitation on the forager's intake rate, a constraint that potentially
      cannot be alleviated by enlarging digestive capacity. Hence, physiological
      flexibility may have a differential effect on intake of different prey types, and
      consequently on dietary preferences. We tested this effect in red knots (Calidris
      canutus canutus), medium-sized migratory shorebirds that feed on hard-shelled,
      usually mollusc, prey. Because they ingest their prey whole and crush the shell
      in their gizzard, the intake rate of red knots is generally constrained by
      digestive capacity. However, one of their main prey, the bivalve Loripes
      lucinalis, imposes a toxin constraint due to its symbiosis with sulphide
      oxidizing bacteria. We manipulated gizzard sizes of red knots through prolonged
      exposure to hard-shelled or soft foods. We then measured maximum intake rates of
      toxic Loripes versus a non-toxic bivalve, Dosinia isocardia. We found that intake
      of Dosinia exponentially increased with gizzard mass, confirming earlier results
      with non-toxic prey, whereas intake of Loripes was independent of gizzard mass.
      Using linear programming, we show that this leads to markedly different expected
      diet preferences in red knots that try to maximize energy intake rate with a
      small versus a large gizzard. Intra- and inter-individual variation in digestive
      capacity is found in many animal species. Hence, the here proposed functional
      link with individual differences in foraging decisions may be general. We
      emphasize the potential relevance of individual variation in physiology when
      studying trophic interactions. 

PMID- 26287953
TI  - Mercury and selenium accumulation in the Colorado River food web, Grand Canyon,
      USA.
AB  - Mercury (Hg) and selenium (Se) biomagnify in aquatic food webs and are toxic to
      fish and wildlife. The authors measured Hg and Se in organic matter,
      invertebrates, and fishes in the Colorado River food web at sites spanning 387
      river km downstream of Glen Canyon Dam (AZ, USA). Concentrations were relatively
      high among sites compared with other large rivers (mean wet wt for 6 fishes was
      0.17-1.59 MUg g(-1) Hg and 1.35-2.65 MUg g(-1) Se), but consistent longitudinal
      patterns in Hg or Se concentrations relative to the dam were lacking. Mercury
      increased (slope = 0.147) with delta(15) N, a metric of trophic position,
      indicating biomagnification similar to that observed in other freshwater systems.
      Organisms regularly exceeded exposure risk thresholds for wildlife and humans (6
      100% and 56-100% of samples for Hg and Se, respectfully, among risk thresholds).
      In the Colorado River, Grand Canyon, Hg and Se concentrations pose exposure risks
      for fish, wildlife, and humans, and the findings of the present study add to a
      growing body of evidence showing that remote ecosystems are vulnerable to long
      range transport and subsequent bioaccumulation of contaminants. Management of
      exposure risks in Grand Canyon will remain a challenge, as sources and transport
      mechanisms of Hg and Se extend far beyond park boundaries.

PMID- 26287954
TI  - Binge Drinking Associations with Patrons' Risk Behaviors and Alcohol Effects
      after Leaving a Nightclub: Sex Differences in the "Balada com Ciencia" Portal
      Survey Study in Brazil.
AB  - The purpose of the present study was to investigate the potential associations of
      binge drinking detected at the exit of nightclubs and risk behaviors and alcohol
      effects just after leaving the venue in a representative sample of Brazilian
      nightclub patrons according to sex. For this purpose, a portal survey study
      called Balada com Ciencia was conducted in 2013 in the megacity of Sao Paulo,
      Brazil, using a two-stage cluster sampling survey design. Individual-level data
      were collected in 2422 subjects at the entrance and 1822 subjects at the exit of
      31 nightclubs, and breath alcohol concentration (BrAC) was measured using a
      breathalyzer. The following day, 1222 patrons answered an online follow-up survey
      that included questions about risk behaviors and alcohol effects practiced just
      after leaving the nightclub. Weighted logistic regressions were used to analyze
      binge drinking associated with risk behaviors by sex. For both sexes, the most
      prevalent risk behaviors practiced after leaving a nightclub were drinking and
      driving (men=27.9%; women=20.4%), the use of illicit drugs (men=15.8%;
      women=9.4%) and risky sexual behavior (men=11.4%; women=6.8%). The practice of
      binge drinking increased the behavior of illicit drug use after leaving the
      nightclub by 2.54 times [95% CI: 1.26-5.09] among men who drank and increased the
      risk of an episode of new alcohol use by 5.80 times [95% CI: 1.50-22.44] among
      women who drank. Alcoholic blackouts were more prevalent among men [OR=8.92; 95%
      CI: 3.83-20.80] and women [OR= 5.31; 95% CI: 1.68-16.84] whose BrAC was
      equivalent to binge drinking compared with patrons with a lower BrAC. Public
      policies aiming to reduce patrons' BrAC at the exit of nightclubs, such as staff
      training in responsible beverage service and legislation to prevent alcohol sales
      to drunk individuals, would be useful to protect patrons from the risk behaviors
      associated with binge drinking in nightclubs. 

PMID- 26287955
TI  - A randomized-controlled study to compare the efficacy of sequential therapy with
      standard triple therapy for Helicobacter pylori eradication in an Irish
      population.
AB  - INTRODUCTION: Eradication rates for the standard first-line triple therapy for
      Helicobacter pylori infection have decreased in recent years. Sequential therapy
      has been suggested as an alternative. The efficacy of sequential therapy has not
      been assessed to date in an Irish population. OBJECTIVE: The aim of this study
      was to compare the efficacy of standard triple therapy with sequential therapy
      for H. pylori eradication. PATIENTS AND METHODS: A prospective randomized
      controlled study was carried out. Treatment-naive H. pylori-infected patients
      were randomized to receive either standard triple therapy or sequential therapy.
      RESULTS: In all, 87 eligible patients were recruited into the study, one of whom
      dropped out. Fifty-one per cent (N=44) patients received standard triple therapy
      and 49% (N=42) patients received sequential therapy. The eradication efficacy by
      intention-to-treat analysis was 56.8% [N=25/44; 95% confidence interval (CI) 42.2
      71.4%] for standard triple therapy and 69% (N=29/42; 95% CI 55.0-83.0%) for
      sequential therapy. The eradication rates by per-protocol analysis for standard
      triple therapy and sequential therapy were 61% (N=25/41; 95% CI 46.1-76.0%) and
      69% (N=29/42; 95% CI 55.0-83.0%), respectively. The differences in eradication
      rates for each treatment by either intention-to-treat or per-protocol analysis
      were not statistically significant (P=0.24 and 0.44, respectively). In addition,
      incidence in adverse events was not significantly different between the study
      groups. The most common adverse event reported was mild nausea at 15% (95% CI 7.5
      22.6%). CONCLUSION: Sequential therapy had a nonstatistically significant
      advantage over standard triple therapy in our patient cohort. However,
      eradication rates for both standard triple therapy and sequential therapy were
      suboptimal. Further studies are required to identify potential alternatives to
      standard first-line triple therapy.

PMID- 26287956
TI  - Identification of Race and Ethnicity in Large Databases--Reply.

PMID- 26287957
TI  - Tumor-infiltrating CD8(+) T lymphocytes associated with clinical outcome in anal
      squamous cell carcinoma.
AB  - BACKGROUND: The prognostic significance of tumor-infiltrating CD8(+) T
      lymphocytes in anal squamous cell carcinoma (SCC) remains unclear. We designed
      the study to investigate the association between CD8(+) T cells and clinical
      prognosis among anal SCC patients. METHODS: The density of CD8(+) T cells was
      assessed by immunohistochemistry. The numbers of CD8(+) T cells were counted and
      their relationship with clinicopathological factors and survival was explored.
      RESULTS: A strong positive correlation was noted between intratumoral and
      peritumoral CD8(+) T cells (r = 0.77, P < 0.001). High intratumoral and
      peritumoral CD8(+) T cells was associated with well tumor differentiation, early
      stage diagnosis, and better prognosis (P < 0.05). Better disease-free survival
      rates were demonstrated in patients with high CD8(+) T cell density in
      intratumoral nest (P = 0.01); peritumoral stroma (P = 0.004); and both in
      combination (P = 0.01). High peritumoral CD8(+) T cell was associated with
      overall survival (P = 0.025). In HIV-infected patients, high CD8(+) T cell
      density also had association with disease-free survival (P < 0.05). CONCLUSIONS:
      High tumor-infiltrating CD8(+) T cell density showed the potential to indicate a
      favorable effect on prognosis and survival for anal SCC patients.

PMID- 26287958
TI  - Approximate confidence intervals for moment-based estimators of the between-study
      variance in random effects meta-analysis.
AB  - Moment-based estimators of the between-study variance are very popular when
      performing random effects meta-analyses. This type of estimation has many
      advantages including computational and conceptual simplicity. Furthermore, by
      using these estimators in large samples, valid meta-analyses can be performed
      without the assumption that the treatment effects follow a normal distribution.
      Recently proposed moment-based confidence intervals for the between-study
      variance are exact under the random effects model but are quite elaborate. Here,
      we present a much simpler method for calculating approximate confidence intervals
      of this type. This method uses variance-stabilising transformations as its basis
      and can be used for a very wide variety of moment-based estimators in both the
      random effects meta-analysis and meta-regression models.

PMID- 26287959
TI  - Tungsten Oxides for Photocatalysis, Electrochemistry, and Phototherapy.
AB  - The conversion, storage, and utilization of renewable energy have all become more
      important than ever before as a response to ever-growing energy and environment
      concerns. The performance of energy-related technologies strongly relies on the
      structure and property of the material used. The earth-abundant family of
      tungsten oxides (WOx <=3 ) receives considerable attention in photocatalysis,
      electrochemistry, and phototherapy due to their highly tunable structures and
      unique physicochemical properties. Great breakthroughs have been made in
      enhancing the optical absorption, charge separation, redox capability, and
      electrical conductivity of WOx <=3 through control of the composition, crystal
      structure, morphology, and construction of composite structures with other
      materials, which significantly promotes the efficiency of processes and devices
      based on this material. Herein, the properties and synthesis of WOx <=3 family
      are reviewed, and then their energy-related applications are highlighted,
      including solar-light-driven water splitting, CO2 reduction, and pollutant
      removal, electrochromism, supercapacitors, lithium batteries, solar and fuel
      cells, non-volatile memory devices, gas sensors, and cancer therapy, from the
      aspect of function-oriented structure design and control. 

PMID- 26287960
TI  - Pregnant patients' risk perception of prenatal test results with uncertain fetal
      clinical significance: ultrasound versus advanced genetic testing.
AB  - OBJECTIVE: A common concern of utilizing prenatal advanced genetic testing is
      that a result of uncertain clinical significance will increase patient anxiety.
      However, prenatal ultrasound may also yield findings of uncertain significance,
      such as 'soft markers' for fetal aneuploidy, or findings with variable prognosis,
      such as mild ventriculomegaly. In this study we compared risk perception
      following uncertain test results from each modality. METHODS: A single survey
      with repeated measures design was administered to 133 pregnant women. It included
      'intolerance of uncertainty' questions, two hypothetical scenarios involving
      prenatal ultrasound or advanced genetic testing, and response questions. The
      primary outcome was risk perception score. RESULTS: Risk perception did not vary
      significantly between ultrasound and genetic scenarios (p = 0.17). The genetic
      scenario scored a higher accuracy (p = 0.04) but lower sense of empowerment (p =
      0.01). Furthermore, patients were more likely to seek additional testing after an
      ultrasound than after genetic testing (p = 0.05). There were no differences in
      other secondary outcomes including perception of life-altering consequences and
      hypothetical worry, anxiety, confusion, or medical care decisions. CONCLUSIONS:
      Our data suggest that uncertain findings on prenatal genetic testing do not
      elicit a higher perception of risk or anxiety when compared to ultrasound
      findings of comparable uncertainty. (c) 2015 John Wiley & Sons, Ltd.

PMID- 26287961
TI  - A Longitudinal Study of Growth, Sex Steroids, and IGF-1 in Boys With
      Physiological Gynecomastia.
AB  - CONTEXT: Physiological gynecomastia is common and affects a large proportion of
      otherwise healthy adolescent boys. It is thought to be caused by an imbalance
      between estrogen and testosterone, although this is rarely evident in analyses of
      serum. OBJECTIVE: This study aimed to describe the frequency of physiological
      gynecomastia and to determine possible etiological factors (eg, auxology and
      serum hormone levels) in a longitudinal setup. DESIGN, SETTINGS, AND
      PARTICIPANTS: A prospective cohort study of 106 healthy Danish boys (5.8-16.4
      years) participated in the longitudinal part of the COPENHAGEN Puberty Study. The
      boys were examined every 6 months during an 8-year follow-up. Median number of
      examinations was 10 (2-15). MAIN OUTCOME MEASUREMENTS: Blood samples were
      analyzed for FSH, LH, testosterone, estradiol, SHBG, inhibin B, anti-Mullerian
      hormone, IGF-1, and IGF binding protein-3 by immunoassays. Auxological
      parameters, pubertal development, and the presence of gynecomastia were evaluated
      at each visit. RESULTS: Fifty-two of 106 boys (49%) developed gynecomastia, of
      which 10 (19%) presented with intermittent gynecomastia. Boys with physiological
      gynecomastia reached peak height velocity at a significantly younger age than
      boys who did not develop gynecomastia (13.5 versus 13.9 years, P = .027), and
      they had significantly higher serum levels of IGF-1 (P = .000), estradiol (P =
      .013), free testosterone (P < .001), and FSH (P = .030) during pubertal
      transition. However, no differences in serum LH or in the estradiol to
      testosterone ratio were found. CONCLUSIONS: Gynecomastia is frequent in pubertal
      boys. Increased IGF-1 levels and pubertal growth appear to be associated, whereas
      changes in estrogen to testosterone ratio seem negligible.

PMID- 26287962
TI  - Extracting physical chemistry from mechanics: a new approach to investigate DNA
      interactions with drugs and proteins in single molecule experiments.
AB  - In this review we focus on the idea of establishing connections between the
      mechanical properties of DNA-ligand complexes and the physical chemistry of DNA
      ligand interactions. This type of connection is interesting because it opens the
      possibility of performing a robust characterization of such interactions by using
      only one experimental technique: single molecule stretching. Furthermore, it also
      opens new possibilities in comparing results obtained by very different
      approaches, in particular when comparing single molecule techniques to ensemble
      averaging techniques. We start the manuscript reviewing important concepts of DNA
      mechanics, from the basic mechanical properties to the Worm-Like Chain model.
      Next we review the basic concepts of the physical chemistry of DNA-ligand
      interactions, revisiting the most important models used to analyze the binding
      data and discussing their binding isotherms. Then, we discuss the basic features
      of the single molecule techniques most used to stretch DNA-ligand complexes and
      to obtain "force * extension" data, from which the mechanical properties of the
      complexes can be determined. We also discuss the characteristics of the main
      types of interactions that can occur between DNA and ligands, from covalent
      binding to simple electrostatic driven interactions. Finally, we present a
      historical survey of the attempts to connect mechanics to physical chemistry for
      DNA-ligand systems, emphasizing a recently developed fitting approach useful to
      connect the persistence length of DNA-ligand complexes to the physicochemical
      properties of the interaction. Such an approach in principle can be used for any
      type of ligand, from drugs to proteins, even if multiple binding modes are
      present. 

PMID- 26287963
TI  - Understanding the Role of NH4F and Al2O3 Surface Co-modification on Lithium
      Excess Layered Oxide Li1.2Ni0.2Mn0.6O2.
AB  - In this work we prepared Li1.2Ni0.2Mn0.6O2 (LNMO) using a hydroxide co
      precipitation method and investigated the effect of co-modification with NH4F and
      Al2O3. After surface co-modification, the first cycle Coulombic efficiency of
      Li1.2Ni0.2Mn0.6O2 improved from 82.7% to 87.5%, and the reversible discharge
      capacity improved from 253 to 287 mAh g(-1) at C/20. Moreover, the rate
      capability also increased significantly. A combination of neutron diffraction
      (ND), high-resolution transmission electron microscopy (HRTEM), aberration
      corrected scanning transmission electron microscopy (a-STEM)/electron energy loss
      spectroscopy (EELS), and X-ray photoelectron spectroscopy (XPS) revealed the
      changes of surface structure and chemistry after NH4F and Al2O3 surface co
      modification while the bulk properties showed relatively no changes. These
      complex changes on the material's surface include the formation of an amorphous
      Al2O3 coating, the transformation of layered material to a spinel-like phase on
      the surface, the formation of nanoislands of active material, and the partial
      chemical reduction of surface Mn(4+). Such enhanced discharge capacity of the
      modified material can be primarily assigned to three aspects: decreased
      irreversible oxygen loss, the activation of cathode material facilitated with
      preactivated Mn(3+) on the surface, and stabilization of the Ni-redox pair. These
      insights will provide guidance for the surface modification in high-voltage
      cathode battery materials of the future. 

PMID- 26287964
TI  - Transcatheter Arterial Embolization Alone for Giant Hepatic Hemangioma.
AB  - Giant hepatic hemangioma is a benign liver condition that may be treated using
      surgery. We studied the digital subtraction angiographic (DSA) characteristics of
      giant hepatic hemangioma, and the effectiveness of transcatheter arterial
      embolization (TAE) alone for its treatment. This was a retrospective study of 27
      patients diagnosed with giant hepatic hemangioma and treated with TAE alone
      (using lipiodol mixed with pingyangmycin) at the Division of Hepatobiliary and
      Pancreatic Surgery, First Affiliated Hospital, Zhejiang University, between
      January 2010 and March 2013. The feeding arteries were identified using DSA. All
      patients were followed up for between three weeks and 12 months. Changes in tumor
      diameter and symptoms were observed. The 27 patients included had giant hepatic
      hemangiomas ranging from 5.3 to 24.5 cm (mean, 11.24+/-5.08 cm) in the right (n =
      13), left (n = 1) or both (n = 13) lobes. Preoperative hepatic angiography showed
      multiple abnormal vascular lakes in the early phase, known as the "early leaving
      but late returning, hanging nut on a twig" sign. On the day after TAE, hepatic
      transaminase levels were increased (ALT: 22.69+/-17.95 to 94.88+/-210.32 U/L;
      ALT: 24.00+/-12.37 to 99.70+/-211.54 U/L; both P<0.05), but not total bilirubin.
      Six patients complained of abdominal pain, and 12 experienced transient fever. In
      the months after TAE, tumor size decreased (baseline: 11.24+/-5.08; 3 months:
      8.95+/-4.33; 6 months: 7.60+/-3.90 cm; P<0.05), and the patients' condition
      improved. These results indicated that TAE was effective and safe for treating
      giant hepatic hemangioma. TAE may be a useful alternative to surgery for the
      treatment of hepatic hemangioma. 

PMID- 26287965
TI  - Using Longitudinal Data to Understand Changes in Consistent Contraceptive Use.
AB  - CONTEXT: Most studies of contraceptive behavior rely on cross-sectional data and
      are unable to adequately measure fluctuations in contraceptive use or changes in
      circumstances and attitudes that are likely to be associated with this outcome.
      METHODS: Between November 2012 and May 2014, four waves of data were gathered
      from a national sample of 1,842 women aged 18-39 at baseline. Cross-tabulations
      were used to examine change and stability in time-varying characteristics
      theorized to be associated with consistent contraceptive use. Random-effects and
      fixed-effects logistic regression models were used to examine variables
      associated with consistent contraceptive use. RESULTS: While a majority of women
      were at risk of unintended pregnancy during each survey period, only 42% were at
      risk during all four. Random-effects logistic regression analysis revealed that
      the odds of being a consistent contraceptive user were 10 times as high for a
      woman who expressed a strong pregnancy avoidance attitude as for a woman who had
      a weak attitude. This strong association was confirmed in the fixed-effects
      model. However, having a strong desire to avoid pregnancy was not static; among
      women at risk of unintended pregnancy during at least one survey period, 53%
      reported a change in attitude. CONCLUSIONS: These findings build on prior
      research suggesting that pregnancy avoidance attitudes are an important motivator
      for contraceptive use. It is critical to recognize that the context in which many
      women make decisions about pregnancy and contraceptive use changes over
      relatively short periods of time.

PMID- 26287966
TI  - Phytoplankton Communities Exhibit a Stronger Response to Environmental Changes
      than Bacterioplankton in Three Subtropical Reservoirs.
AB  - The simultaneous analysis of multiple components of ecosystems is crucial for
      comprehensive studies of environmental changes in aquatic ecosystems, but such
      studies are rare. In this study, we analyzed simultaneously the bacterioplankton
      and phytoplankton communities in three Chinese subtropical reservoirs and
      compared the response of these two components to seasonal environmental changes.
      Time-lag analysis indicated that the temporal community dynamics of both
      bacterioplankton and phytoplankton showed significant directional changes, and
      variance partitioning suggested that the major reason was the gradual improvement
      of reservoir water quality from middle eutrophic to oligo-mesotrophic levels
      during the course of our study. In addition, we found a higher level of temporal
      stability or stochasticity in the bacterioplankton community than in the
      phytoplankton community. Potential explanations are that traits associated with
      bacteria, such as high abundance, widespread dispersal, potential for rapid
      growth rates, and rapid evolutionary adaptation, may underlie the different
      stability or stochasticity of bacterioplankton and phytoplankton communities to
      the environmental changes. In addition, the indirect response of bacterioplankton
      to nitrogen and phosphorus may result in the fact that environmental
      deterministic selection was stronger for the phytoplankton than for the
      bacterioplankton communities. 

PMID- 26287967
TI  - GATA2 rs2335052 Polymorphism Predicts the Survival of Patients with Colorectal
      Cancer.
AB  - BACKGROUND: GATA binding protein 2 (GATA2) is a transcription factor that has
      essential roles in hematologic malignancies and progression of various solid
      tumors. Our previous studies suggested that high GATA2 expression is associated
      with recurrence of colorectal cancer (CRC). However, the influence of GATA2
      single nucleotide polymorphisms (SNPs) on the survival of CRC remains unknown.
      METHODS: We genotyped GATA2 SNP rs2335052 using Sanger sequencing after PCR
      amplification, and determined GATA2 expression by immunohistochemistry in a
      cohort of 180 CRC patients. Kaplan-Meier survival analysis and Cox proportional
      hazard regression were used to analyze the association between the GATA2
      rs2335052 genotypes and the clinical outcome of CRC. RESULTS: We found that there
      was no significant correlation between the rs2335052 genotypes and the expression
      of GATA2. However, the Kaplan-Meier survival analysis suggested that the carriers
      of the A-allele of SNP rs2335052 were significantly associated with increased
      risk of recurrence and reduced disease-free survival (DFS), compared with those
      carrying the variant genotype of GG in rs2335052 (P = 0.021). Moreover,
      univariate and multivariate Cox regression analyses revealed that GATA2 SNP
      rs2335052 was an independent risk factor for the DFS of CRC patients. CONCLUSION:
      Our results demonstrated that GATA2 SNP rs2335052 is an independent predictor for
      prognosis of CRC patients. This raised the possibility that SNP rs2335052 may
      serve as a potential indicator for predicting recurrence of CRC after curative
      colectomy.

PMID- 26287968
TI  - Xeno-Klotho Inhibits Parathyroid Hormone Signaling.
AB  - Although fibroblast growth factor (FGF) 23 was recently identified as a
      phosphatonin that influences vitamin D metabolism, the underlying signaling
      mechanisms remain unclear. FGF23 elevates the renal levels of membrane-associated
      klotho as well as soluble klotho. Klotho is expressed on distal tubules. Upon
      enzymatic cleavage, soluble klotho is released into the renal interstitial space
      and then into the systemic circulation. The expression of 25-hydroxyvitamin D3
      1alpha-hydroxylase (1-OH) on proximal tubular cells is controlled by parathyroid
      hormone (PTH). Klotho binds to various membrane proteins to alter their function.
      Here, the interaction between the PTH receptor and klotho was studied using
      various approaches, including immunoprecipitation, in vitro cell culture, and in
      vivo animal experiments. Immunoprecipitation studies demonstrate, for the first
      time, that recombinant human klotho protein interacts with human PTH receptors to
      inhibit the binding of human PTH. Furthermore, when applied to human proximal
      tubular cells, recombinant human klotho suppresses PTH-stimulated generation of
      inositol trisphosphate in vitro. Moreover, PTH-induced increase of cyclic AMP
      secretion and 1alpha,25-dihydroxyvitamin D3 (1,25VD) was attenuated by
      recombinant human klotho in vivo. In addition, recombinant human klotho inhibits
      the expression of 1-OH by PTH both in vitro and in vivo. These results suggest
      that free klotho mediates the FGF23-induced inhibition of 1,25VD synthesis.

PMID- 26287969
TI  - The Decrease of Peripheral Blood CD4+ T Cells Indicates Abdominal Compartment
      Syndrome in Severe Acute Pancreatitis.
AB  - OBJECTIVE: Few data are available on the role of T lymphocytes and inflammatory
      cytokines in abdominal compartment syndrome (ACS) in severe acute pancreatitis
      (SAP). We conducted a retrospective study to assess the risk factors associated
      with ACS in SAP. METHODS: A total of 76 SAP patients who were admitted within 24
      hours after symptom onset in our study. There were 36 patients suffering from ACS
      and 40 from intra-abdominal hypertension (IAH). On the 1st, 3rd and 7th days
      after hospital admission, the following variables were assessed: serum value of C
      reactive protein (CRP), and the proportions of peripheral CD4+ and CD8+ T
      lymphocytes. Acute Physiology and Chronic Health Evaluation II (APACHE II) score,
      and computed tomography severity index (CTSI) score were assessed on days 1 and 7
      after hospitalization. RESULTS: Compared with the patients with IAH, ACS patients
      showed statistically higher CRP value on 7th day after hospital admission,
      proportions of CD4+ T cells on days 1, 3, 7 and CD4+/CD8+ ratio on day 1 were
      significantly lower (P < 0.05, respectively). A CD4+ T cell proportion of 30.3%
      on the 1st day indicated ACS with an area under the curve (AUC) of 0.774, a
      sensitivity with 82.5% and specificity with 72.0%, respectively.
      Sensitivity/specificity for predicting ACS in SAP patients on day 1 was
      70.0%/68.0% for CD4+/CD8+ ratio, 72.2%/65.0% for APACHE II score. CONCLUSIONS:
      The reduction of peripheral blood CD4+ T lymphocytes is associated with ACS in
      SAP, and may act as a potential predictor of ACS in SAP.

PMID- 26287970
TI  - Clinical, Pathological, and Surgical Outcomes for Adult Pineoblastomas.
AB  - INTRODUCTION: Pineoblastomas are uncommon primitive neuroectodermal tumors that
      occur mostly in children; they are exceedingly rare in adults. Few published
      reports have compared the various aspects of these tumors between adults and
      children. METHODS: The authors report a series of 12 pineoblastomas in adults
      from 2 institutions over 24 years. The clinical, radiologic, and pathologic
      features and clinical outcomes were compared with previously reported cases in
      children and adults. RESULTS: Patient age ranged from 24 to 81 years, and all but
      1 patient exhibited symptoms of obstructive hydrocephalus. Three patients
      underwent gross total resection, and subtotal resection was performed in 3
      patients. Diagnostic biopsy specimens were obtained in an additional 6 patients.
      Pathologically, the tumors had the classical morphologic and immunohistochemical
      features of pineoblastomas. Postoperatively, 10 patients received radiotherapy,
      and 5 patients received chemotherapy. Compared with previously reported cases,
      several differences were noted in clinical outcomes. Of the 12 patients, only 5
      (42%) died of their disease (average length of survival, 118 months); 5 patients
      (42%) are alive with no evidence of disease (average length of follow-up, 92
      months). One patient died of unrelated causes, and one was lost to follow-up.
      Patients with subtotal resections or diagnostic biopsies did not suffer a worse
      prognosis. Of the 9 patients with biopsy or subtotal resection, 4 are alive, 4
      died of their disease, and 1 died of an unrelated hemorrhagic cerebral
      infarction. CONCLUSIONS: Although this series is small, the data suggest that
      pineoblastomas in adults have a less aggressive clinical course than in children.

PMID- 26287971
TI  - Introduction of the 2015 Recipient of the Clark P. Read Mentor Award.

PMID- 26287972
TI  - Identification of the Mitochondrial Heme Metabolism Complex.
AB  - Heme is an essential cofactor for most organisms and all metazoans. While the
      individual enzymes involved in synthesis and utilization of heme are fairly well
      known, less is known about the intracellular trafficking of porphyrins and heme,
      or regulation of heme biosynthesis via protein complexes. To better understand
      this process we have undertaken a study of macromolecular assemblies associated
      with heme synthesis. Herein we have utilized mass spectrometry with
      coimmunoprecipitation of tagged enzymes of the heme biosynthetic pathway in a
      developing erythroid cell culture model to identify putative protein partners.
      The validity of these data obtained in the tagged protein system is confirmed by
      normal porphyrin/heme production by the engineered cells. Data obtained are
      consistent with the presence of a mitochondrial heme metabolism complex which
      minimally consists of ferrochelatase, protoporphyrinogen oxidase and
      aminolevulinic acid synthase-2. Additional proteins involved in iron and
      intermediary metabolism as well as mitochondrial transporters were identified as
      potential partners in this complex. The data are consistent with the known
      location of protein components and support a model of transient protein-protein
      interactions within a dynamic protein complex. 

PMID- 26287973
TI  - Race, Mineral Homeostasis and Mortality in Patients with End-Stage Renal Disease
      on Dialysis.
AB  - BACKGROUND: Abnormalities in mineral homeostasis are ubiquitous in patients on
      dialysis, and influenced by race. In this study, we determine the race-specific
      relationship between mineral parameters and mortality in patients initiating
      hemodialysis. METHODS: We measured the levels of fibroblast growth factor 23
      (FGF23) and 25-hydroxyvitamin D (25 D) in 184 African American and 327 non
      African American hemodialysis patients who enrolled between 1995 and 1998 in the
      Choices for Healthy Outcomes in Caring for ESRD Study. Serum calcium, phosphorus,
      parathyroid hormone (PTH) and total alkaline phosphatase levels were averaged
      from clinical measurements during the first 4.5 months of dialysis. We evaluated
      the associated prospective risk of mortality using multivariable Cox proportional
      hazards models stratified by race. RESULTS: PTH and total alkaline phosphatase
      levels were higher, whereas calcium, phosphorus, FGF23 and 25 D levels were lower
      in African Americans compared to those of non-African Americans. Higher serum
      phosphorus and FGF23 levels were associated with greater mortality risk overall;
      however, phosphorus was only associated with risk among African Americans (HR
      5.38, 95% CI 2.14-13.55 for quartile 4 vs. 1), but not among non-African
      Americans (p-interaction = 0.04). FGF23 was associated with mortality in both
      groups, but more strongly in African Americans (HR 3.91, 95% CI 1.74-8.82 for
      quartiles 4 vs. 1; p-interaction = 0.09). Serum calcium, PTH, and 25 D levels
      were not consistently associated with mortality. The lowest and highest quartiles
      of total alkaline phosphatase were associated with higher mortality risk, but
      this did not differ by race (p-interaction = 0.97). CONCLUSIONS: Aberrant
      phosphorus homeostasis, reflected by higher phosphorus and FGF23, may be a risk
      factor for mortality in patients initiating hemodialysis, particularly among
      African Americans.

PMID- 26287974
TI  - Increased Reward-Related Behaviors during Sleep and Wakefulness in Sleepwalking
      and Idiopathic Nightmares.
AB  - BACKGROUND: We previously suggested that abnormal sleep behaviors, i.e., as found
      in parasomnias, may often be the expression of increased activity of the reward
      system during sleep. Because nightmares and sleepwalking predominate during REM
      and NREM sleep respectively, we tested here whether exploratory excitability, a
      waking personality trait reflecting high activity within the mesolimbic
      dopaminergic (ML-DA) system, may be associated with specific changes in REM and
      NREM sleep patterns in these two sleep disorders. METHODS: Twenty-four
      unmedicated patients with parasomnia (12 with chronic sleepwalking and 12 with
      idiopathic nightmares) and no psychiatric comorbidities were studied. Each
      patient spent one night of sleep monitored by polysomnography. The Temperament
      and Character Inventory (TCI) was administered to all patients and healthy
      controls from the Geneva population (n = 293). RESULTS: Sleepwalkers were more
      anxious than patients with idiopathic nightmares (Spielberger Trait anxiety/STAI
      T), but the patient groups did not differ on any personality dimension as
      estimated by the TCI. Compared to controls, parasomnia patients (sleepwalkers
      together with patients with idiopathic nightmares) scored higher on the Novelty
      Seeking (NS) TCI scale and in particular on the exploratory
      excitability/curiosity (NS1) subscale, and lower on the Self-directedness (SD)
      TCI scale, suggesting a general increase in reward sensitivity and impulsivity.
      Furthermore, parasomnia patients tended to worry about social separation
      persistently, as indicated by greater anticipatory worry (HA1) and dependence on
      social attachment (RD3). Moreover, exploratory excitability (NS1) correlated
      positively with the severity of parasomnia (i.e., the frequency of self-reported
      occurrences of nightmares and sleepwalking), and with time spent in REM sleep in
      patients with nightmares. CONCLUSIONS: These results suggest that patients with
      parasomnia might share common waking personality traits associated to reward
      related brain functions. They also provide further support to the notion that
      reward-seeking networks are active during human sleep.

PMID- 26287975
TI  - Suboptimal Serum alpha-Tocopherol Concentrations Observed among Younger Adults
      and Those Depending Exclusively upon Food Sources, NHANES 2003-20061-3.
AB  - Vitamin E is an essential nutrient for human health, with an established function
      as a lipid-soluble antioxidant that protects cell membranes from free radical
      damage. Low vitamin E status has been linked to multiple health outcomes,
      including total mortality. With vitamin E being identified as a 'shortfall
      nutrient' because >90% of American adults are not consuming recommended amounts
      of vitamin E, we aimed to determine the prevalence of both clinical vitamin E
      deficiency (serum alpha-tocopherol concentration < 12 MUmol/L) and failure to
      meet a criterion of vitamin E adequacy, serum alpha-tocopherol concentration of
      30 MUmol/L, based on the Estimated Average Requirement (EAR) and lowest mortality
      rate in the Alpha-Tocopherol Beta-Carotene (ATBC) study. The most recent
      nationally-representative cross-sectional data (2003-2006) among non
      institutionalized US citizens with available serum concentrations of alpha
      tocopherol from the National Health and Nutrition Examination Survey (NHANES);
      Centers for Disease Control and Prevention were analyzed. Serum alpha-tocopherol
      distributions were compared between those reporting consumption of food without
      supplement use (FOOD) and food and supplement use (FOOD+DS) by sex, age, and
      race/ethnicity. Only 1% of the US population is clinically deficient. FOOD
      consumers have lower average alpha-tocopherol levels (24.9+/- 0.2 MUmol/L) than
      FOOD+DS users (33.7 +/- 0.3 MUmol/L), even when adjusted for total cholesterol.
      Using a criterion of adequacy of 30 MUmol/L, 87% of persons 20-30 y and 43% of
      those 51+y had inadequate vitamin E status (p<0.01). A significant greater
      prevalence of FOOD compared to FOOD+DS users did not meet the criterion of
      adequacy which was based on the EAR and low ATBC mortality rate consistently
      across age, sex, and race/ethnic groups. The prevalence of inadequate vitamin E
      levels is significantly higher among non-users of dietary supplements. With
      declining usage of vitamin E supplements, the population should be monitored for
      changes in vitamin E status and related health outcomes.

PMID- 26287977
TI  - Correction: Motion Tracker: Camera-Based Monitoring of Bodily Movements Using
      Motion Silhouettes.

PMID- 26287976
TI  - The intersection of structurally traumatized communities and substance use
      treatment: Dominant discourses and hidden themes.
AB  - This article reviews multidisciplinary literature to propose a structurally
      traumatized communities theoretical framework relating to three major topics: (a)
      addiction as an equal opportunity disease, (b) the psychology of marijuana use,
      and (c) anger and rage. From an ecological and structural perspective, the
      socially defined themes of stigma and stereotypes interplay with sociopolitical,
      historical, and cultural forces that contribute to substance use and addiction
      among African Americans and the treatment success gap that they experience in
      drug treatment. Empathy serves as an underlying mediating construct in clinical
      training and accreditation standards, inducing a systematic improvement in
      programmatic service delivery.

PMID- 26287978
TI  - Reply to direct-acting antiviral drugs and hepatitis C virus: A therapeutic
      revolution?

PMID- 26287979
TI  - Four new fawcettimine-related alkaloids from Phlegmariurus squarrosus.
AB  - Four new fawcettimine-related alkaloids (1-4), together with 17 known ones, were
      isolated from club moss Phlegmariurus squarrosus. Notably, compound 1 was the
      derivative of lycoflexine with an unprecedented additional methyl group at C-17.
      Their structures were determined by extensive spectroscopic analysis, including
      1D and 2D NMR, and HR-MS, as well as by comparison with the literature data. All
      new compounds were tested for their beta-site amyloid precursor protein (APP)
      cleaving enzyme 1 (BACE1) and acetylcholinesterase (AChE) inhibitory activities. 

PMID- 26287980
TI  - Valvular calcification and left ventricular modifying in peritoneal dialysis
      patients.
AB  - BACKGROUND: Cardiac valve calcification (CVC) and left ventricular (LV)
      alterations are frequent complication in end-stage renal disease (ESRD). We
      determined the prevalence of CVC and LV hypertrophy (LVH) in ESRD patients before
      renal replacement therapy and 12 months after peritoneal dialysis (PD). METHODS:
      A prospective longitudinal of 50 incident PD patients was studied. Demographic
      and clinical data were recorded and blood assayed at baseline and after 1-year of
      follow-up. CVC and LVH were evaluated by M-mode two-dimensional echocardiography.
      RESULTS: CVC of the mitral and aortic valves and of both valves were noted in 30,
      18 and 10% of patients, respectively. After 12 months of PD regimen, 20% patients
      had aortic, 24% mitral and 8% had calcification of both valves. After one year of
      PD, LVH was 62 and 36% in patients with and without CVC, respectively (p < 0.05).
      Endothelin-1 is an independent predictor of CVC at the baseline, while nitric
      oxide is inversely an independent predictor at the end of follow-up. CONCLUSIONS:
      CVC is associated with LVH in PD patients. These findings identified a potential
      role for monitored markers to be incorporated into therapeutic strategies aimed
      at detection and treatment of cardiovascular complications and prevention
      strategies.

PMID- 26287981
TI  - Study of the Acute Effects of Povidone-Iodine on Conjunctival Bacterial Flora.
AB  - PURPOSE: The purpose of this laboratory study was to assess the effect of
      povidone-iodine (PI) use topically on the conjunctiva in regard to needle bore
      contamination and to compare these results with our previous findings from an
      evaluation of bacterial contamination following gatifloxacin and moxifloxacin
      administration. METHODS: We performed 100 conjunctival 27-gauge needle
      penetrations of both eyes of 13 fresh cadavers. Eyes were then soaked in 10% PI,
      after which conjunctiva was again penetrated 100 times. After conjunctival
      penetration, the needles were irrigated, and the irrigant was assessed for
      bacterial growth. Results were compared with previous work assessing
      fluoroquinolone effectiveness through the same model. RESULTS: We observed a 28%
      (P = 0.003) decrease in bacterial growth and 40% (P < 0.0001) decrease in colony
      counts after PI placement. Differences between the effect of PI versus
      moxifloxacin and gatifloxacin were not statistically significant. CONCLUSIONS:
      There is a greater decrease in bacterial load after treatment with PI for surface
      cultures than for cultures obtained through a needle bore passed through the
      conjunctiva. PI is a superior approach to topical antibiotics to decrease
      conjunctival bacterial load.

PMID- 26287982
TI  - Synthesis and antitumor activity of novel N-substituted carbazole imidazolium
      salt derivatives.
AB  - A series of novel N-substituted carbazole imidazolium salt derivatives has been
      prepared and investigated for their cytotoxic activity against five human tumor
      cell lines by MTS assay. The results indicated that the existence of 5,6-dimethyl
      benzimidazole ring, substitution of the imidazolyl-3-position with a 2
      bromobenzyl or naphthylacyl group, as well as alkyl chain length between
      carbazole and imidazole ring were important for the antitumor activity. Compound
      61, bearing a 2-bromobenzyl substituent at position-3 of the 5,6-dimethyl
      benzimidazole, showed powerful inhibitory activities and was more selective to HL
      60, SMMC-7721, MCF-7 and SW480 cell lines with IC50 values 0.51-2.48 MUM.
      Mechanism of action studies revealed that this new compound could remarkably
      induce cell cycle arrest and apoptosis in SMMC-7721 cells. This work provides
      alternative novel way for future drug development based on carbazole and
      imidazolium salt scaffolds. 

PMID- 26287983
TI  - Interventions for dialysis patients with hepatitis C virus (HCV) infection.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection is common in chronic kidney disease
      (CKD) patients on dialysis, causes chronic liver disease, increases mortality and
      impacts kidney transplant outcomes. Sustained response to the preferred treatment
      with standard or pegylated (PEG) interferon is seen in 39% with side effects
      necessitating treatment discontinuation in 20%. We collated evidence for
      treatment response and harms of interventions for HCV infection in dialysis.
      OBJECTIVES: We aimed to look at the benefits and harms of various interventions
      for HCV infection in CKD patients on HD or peritoneal dialysis, specifically on
      mortality, disease relapse, response to treatment, treatment discontinuation,
      time to recovery, quality of life, cost effectiveness,adverse effects, and other
      outcomes. We aimed to study comparisons of available interventions with a placebo
      or control group, combinations of interventions with placebo or control group,
      interventions with each other singly and in combination, available standard
      interventions with newer treatment modalities. SEARCH METHODS: We searched
      Cochrane Kidney and Transplant's Specialised Register to 24 March 2015 through
      contact with the Trials' Search Co-ordinator. We also checked references of
      reviews, studies and contacted study authors to identify additional studies.
      SELECTION CRITERIA: Randomised controlled trials (RCTs), quasi-RCTs, first period
      of randomised cross-over studies on interventions for HCV in CKD on dialysis were
      considered. DATA COLLECTION AND ANALYSIS: We used standard methodological
      procedures expected by the Cochrane Collaboration and also collected adverse
      effects data listed in included RCTs. MAIN RESULTS: Ten RCTs (361 participants)
      met our inclusion criteria. Five RCTs (152 participants, 134 analysed) with low
      to moderate quality of evidence compared standard recombinant interferon with
      placebo or control. There was no significant difference for mortality (5 studies
      (134 participants): RR 0.89, 95% CI 0.06 to 13.23), relapses (1 study (36
      participants): RR 0.72, 95% CI 0.28 to 1.88), sustained virological response (4
      studies (98 participants): RR 3.25, 95% CI 0.81 to 13.07), treatment
      discontinuation (4 studies (116 participants): RR 4.59, 95% CI 0.49 to 42.69) and
      number with adverse events (5 studies (143 participants): RR 3.56, 95% CI 0.98 to
      13.01). End of treatment response was significantly more for standard interferon
      (5 studies (132 participants): RR 8.62, 95% CI 3.03 to 24.55). There was overall
      low to unclear risk of bias and no significant heterogeneity.One RCT (50
      participants) with moderate quality of evidence compared PEG interferon and
      standard interferon. There was no significant difference in mortality (RR 0.33,
      95% CI 0.01 to 7.81), relapses (RR 0.72, 95% CI 0.41 to 1.25), sustained
      virological response (RR 2.40, 95% CI 0.99 to 5.81), treatment discontinuation
      (RR 0.11, 95% CI 0.01 to 1.96) and number with major adverse events (RR 0.11, 95%
      CI 0.01 to 1.96). End of treatment response was significantly more for PEG
      interferon (RR 1.53, 95% CI 1.09 to 2.15). There was overall low risk of bias.Two
      RCTs (97 participants) with moderate quality of evidence compared two doses of
      two different preparations of PEG interferon. Subgroup analysis comparing high
      and low doses of PEG interferon alpha-2a (135 ug/week versus 90 ug/week) and PEG
      interferon alpha-2b (1 ug/kg versus 0.5 ug/kg body weight/week) found no
      significant difference in mortality (2 studies (97 participants): RR 4.30, 95% CI
      0.76 to 24.33), relapses (1 study (81 participants): RR 1.11, 95% CI 0.45 to
      2.77), end of treatment response (2 studies (97 participants): RR 1.42, 95% CI
      0.51 to 3.90), sustained virological response (2 studies (97 participants): RR
      1.19, 95% CI 0.68 to 2.07), treatment discontinuation (2 studies (97
      participants): RR 1.20, 95% CI 0.63 to 2.28), patients with adverse events (2
      studies (97 participants): RR 1.05, 95% CI 0.61 to 1.83) or serious adverse
      events (2 studies (97 participants): RR 1.24, 95% CI 0.72 to 2.14). Both had
      overall low risk of bias and no significant subgroup differences.Two RCTs (62
      participants) with moderate quality of evidence compared standard or PEG
      interferon alone or in combination with ribavirin. The only reported outcome in
      both was treatment discontinuation which was significantly more with ribavirin in
      the one study (RR 0.34, 95% CI 0.14 to 0.84) and pooled 7/10 in the second.No
      RCTs had data on time to recovery, cost-effectiveness, quality of life, and other
      outcomes and in peritoneal dialysis. AUTHORS' CONCLUSIONS: Our review
      demonstrated that in CKD patients on haemodialysis with HCV infection treatment
      with standard interferon brings about an end of treatment but not a sustained
      virological response and is relatively well tolerated. PEG interferon is more
      effective than standard interferon for end of treatment response but not for
      sustained response; both were equally tolerated. Increasing doses of PEG
      interferon did not improve responses but high and low doses are equally
      tolerated. Addition of ribavirin results in more treatment discontinuation.

PMID- 26287984
TI  - Theoretical kinetic study for methyl levulinate: oxidation by OH and CH3 radicals
      and further unimolecular decomposition pathways.
AB  - Biofuels may represent a promising alternative in terms of energy sustainability
      and emission control. Until recently, simple compounds including only a single
      specific functional group was in the focus of the biofuel research while reported
      data on more complex structures are scarcer. Presence of multiple functional
      groups can make molecules more attractive for oxidative species providing
      attacking site for fast oxidation. Including both a carbonyl and an ester group,
      methyl levulinate (ML) can be such an excellent biofuel candidate due to its
      cellulosic origin, although its combustion kinetics is still unresolved. This
      work reports the first computational kinetic study on methyl levulinate oxidation
      relevant to combustion conditions. Absolute rate constants for H-abstraction
      reactions by OH and CH3 radicals were calculated using the G3//MP2/aug-cc-pVDZ
      level of theory coupled with Transition State Theory (TST). The fate of the
      forming ML radicals was also investigated by computing absolute rate constants
      for beta-scission as well as for H-transfer reactions. The outcomes of this work
      show that the sites between the two functional groups are the most favorable for
      H-abstraction reactions, and that methyl vinyl ketone (MVK) and methyl acrylate
      (MAC) are expected to be the main intermediate products of methyl levulinate
      oxidation. The present results will be useful for further detailed kinetic
      modeling. 

PMID- 26287985
TI  - Fabrication of healthy and disease-mimicking retinal phantoms with tapered foveal
      pits for optical coherence tomography.
AB  - Optical coherence tomography (OCT) has become a standard tool in ophthalmology
      clinics for diagnosing many retinal diseases. Nonetheless, the technical and
      clinical communities still lack a standardized phantom that could aid in
      evaluating and normalizing the many protocols and systems used for diagnosis.
      Existing retinal phantoms are able to mimic the thickness and scattering
      properties of the retinal layers but are unable to model the morphology of the
      foveal pit, particularly the tapering of the retinal layers. This work
      demonstrates a new fabrication procedure that is capable of reliably and
      consistently replicating the shape and tapered appearance of the retinal layers
      near the foveal pit using a combination of spin-coating and replica molding. We
      characterize the effects of using different mold sizes which enable us to achieve
      a range of pit dimensions. We also present a modified procedure to replicate two
      diseased states of the retinal tissue, such as retinal detachment and dry aged
      related macular degeneration. The ability to create an anatomically correct
      foveal pit for healthy and disease-mimicking phantoms will allow for a new
      standard better suited for intra- and inter-system evaluation and for improved
      comparison of retinal segmentation algorithms

PMID- 26287986
TI  - Immunosuppression and probiotics: are they effective and safe?
AB  - This opinion statement discusses indications, efficacy and safety of probiotics
      in immunosuppressed patients. The best evidence available is for the prophylaxis
      of infections in patients after liver transplantation and for patients with liver
      cirrhosis. For other organ transplantations and for bone marrow transplantation
      the efficacy of probiotic interventions has not been proven yet, but in these
      patient groups safety is a concern. Also in critically ill patients, the data on
      efficacy are inconclusive and safety is a concern. In HIV patients and patients
      after major surgery, probiotic bacteria seem to be safe since there are no
      associations with increased risks of side effects. 

PMID- 26287987
TI  - Exhaled nitric oxide as a better diagnostic indicator for evaluating wheeze and
      airway hyperresponsiveness in preschool children.
AB  - OBJECTIVE: Fractional concentration of exhaled nitric oxide (FeNO) is a known
      marker of airway inflammation. The aims of this study were to evaluate FeNO,
      impulse oscillometry (IOS), and spirometry in preschool children and to
      investigate their relationship with wheeze and airway hyperresponsiveness (AHR).
      METHODS: We performed a population-based, cross-sectional study with 561 children
      aged 5-6 years. A total of 544 children completed a modified International Study
      of Asthma and Allergies in Childhood (ISAAC) questionnaire and eligible for the
      study. We measured FeNO, spirometry, methacholine bronchial provocation, and IOS.
      AHR was defined as the induction of a 20% decrease in FEV(1)(PC(20)) by a
      methacholine concentration <=8.0 mg/dL. RESULTS: Children who had wheeze or AHR
      had higher FeNO levels than children without these symptoms. However, neither IOS
      nor spirometry parameters showed significant differences between children with
      wheeze or AHR and those without. FeNO was associated with AHR, whereas IOS or
      spirometry parameters showed no association. Mean FeNO levels were positively
      correlated with a dose-response slope for methacholine, but neither IOS nor
      spirometry parameters showed significant correlations. CONCLUSIONS: FeNO is a
      more sensitive measurement of AHR and wheeze than spirometry or IOS in preschool
      children.

PMID- 26287988
TI  - Like-Charge Guanidinium Pairing between Ligand and Receptor: An Unusual
      Interaction for Drug Discovery and Design?
AB  - A database survey in this study revealed for the first time that there are 227
      counterintuitive like-charge guanidinium pairings (Gdm(+)-Arg pairings) between
      ligands and receptors in the Protein Data Bank, implying the potential
      guanidinium-arginine binding between guanidine-containing drugs and their target
      proteins. Furthermore, there are 145 guanidine-containing molecules in the
      DrugBank, showing the prevalence of guanidinium groups in drugs. It has also been
      reported that the introduction of a guanidinium group forming Gdm(+)-Arg pairing
      improved the potency of the drug by more than 8-fold in a typical case. On the
      basis of the survey, six ligand-protein complexes with typical Gdm(+)-Arg
      pairings were chosen for QM/MM calculations. The calculations at the B97-D/6
      311++g(d,p) level revealed that the interaction could be as strong as -1.0 to 
      2.5 kcal/mol in DMSO and water, comparable to common intermolecular interactions.
      The calculations also unveiled that the Gdm(+)-Arg pairing interactions change
      from repulsive to attractive with the increase of dielectric constant, suggesting
      that the dielectric constant has a general stabilization effect on the Gdm(+)-Arg
      pairing. This study suggested that the like-charge guanidinium pairing
      interaction could be used not only for tuning the physical and chemical
      properties of drug leads but also for improving ligand binding affinity. 

PMID- 26287989
TI  - Development and Validation of a Lateral Flow Immunoassay for the Rapid Screening
      of Okadaic Acid and All Dinophysis Toxins from Shellfish Extracts.
AB  - A single-step lateral flow immunoassay was developed and validated to detect
      okadaic acid (OA) and dinophysis toxins (DTXs), which cause diarrhetic shellfish
      poisoning. The performance characteristics of the test were investigated, in
      comparison to reference methods (liquid chromatography tandem mass spectrometry
      and/or bioassay), using both spiked and naturally contaminated shellfish. A
      portable reader was used to generate a qualitative result, indicating the absence
      or presence of OA-group toxins, at concentrations relevant to the maximum
      permitted level (MPL). Sample homogenates could be screened in 20 min (including
      extraction and assay time) for the presence of free toxins (OA, DTX1, DTX2). DTX3
      detection could be included with the addition of a hydrolysis procedure. No
      matrix effects were observed from the species evaluated (mussels, scallops,
      oysters, and clams). Results from naturally contaminated samples (n = 72)
      indicated no false compliant results and no false noncompliant results at <50%
      MPL. Thus, the development of a new low-cost but highly effective tool for
      monitoring a range of important phycotoxins has been demonstrated. 

PMID- 26287990
TI  - Efficacy of automated tumor-feeder detection software using cone-beam computed
      tomography technology in transarterial embolization through extrahepatic
      collateral vessels for malignant hepatic tumors.
AB  - AIM: We evaluated the performance of automated tumor-feeder detection (AFD)
      software using cone-beam computed tomography technology in identifying tumor
      feeders of extrahepatic collaterals. METHODS: AFD was prospectively used in
      superselective transarterial chemoembolization (TACE) or embolization (TAE) of
      extrahepatic collaterals for 29 hepatocellular carcinomas and one liver
      metastasis (mean tumor diameter +/- standard deviation, 28 +/- 15.6 mm) in 25
      patients. The detectability of extrahepatic tumor-feeders with non-selective
      digital subtraction angiography (DSA) and AFD was evaluated and compared using a
      chi(2) -test. Tumor response of target lesions in each patient at 2-3 months
      after treatment was evaluated using the modified Response Evaluation Criteria in
      Solid Tumors. Complications were also evaluated. RESULTS: Of 46 tumor-feeders,
      non-selective DSA and AFD could identify 26 and 44, respectively (P < 0.001).
      Regarding the origin of tumor-feeders, both non-selective DSA and AFD could
      identify 14 of 15, six of seven and two of two tumor-feeders of the right
      inferior phrenic, omental and right renal capsular artery, respectively. In the
      cystic and left gastric or right colic artery, AFD could identify 13 of 13 and
      nine of nine tumor-feeders but non-selective DSA could identify only three of 13
      and one of nine, respectively (P < 0.001). Complete response was obtained in 15
      patients, partial response in six, stable disease in three and progressive
      disease in one. No severe complications developed except for right pleural
      effusion after embolization of the right inferior phrenic artery. CONCLUSION: AFD
      has a sufficient ability to identify extrahepatic tumor-feeders and may improve
      the safety and local effects of TACE/TAE of extrahepatic collaterals.

PMID- 26287991
TI  - Outpatient transcervical microwave myolysis assisted by transabdominal ultrasonic
      guidance for menorrhagia caused by submucosal myomas.
AB  - PURPOSE: The aim of this paper was to evaluate the effectiveness in day clinics
      of microwave endometrial ablation (MEA) on transcervical microwave myolysis for
      patients with menorrhagia caused by submucosal myomas. MATERIALS AND METHODS:
      Thirty-five outpatients (average age 44.8 +/- 5.2 years (mean +/- SD), range 34
      58) with a single submucosal myoma that was 4-7 cm (5.5 +/- 2.1 cm) in size
      underwent MEA with transcervical microwave myolysis using a specifically
      developed transabdominal ultrasound probe attachment for transcervical puncture.
      Primary outcomes were the changes in the blood haemoglobin level and the volume
      of myoma before and after the treatment. Secondary outcomes were the improvement
      in menorrhagia and satisfaction after the operation, assessed by visual analogue
      scale (VAS). RESULTS: The mean operation time was 27.9 +/- 13.6 min. The myomas
      had shrunk by 56.2% at 3 months and 73.8% at >=6 months after the operation.
      Blood haemoglobin levels had increased significantly at 3 months (10.2 +/- 2.0
      vs. 12.7 +/- 1.2, p < 0.001). The average VAS assessment of menstrual bleeding
      had decreased to 1.7 +/- 1.7 at 3 months after the operation (preoperative VAS =
      10). The average VAS score for feelings of satisfaction 3 months after the
      operation was 9.8 +/- 0.5 (full score = 10). CONCLUSIONS: MEA with transcervical
      microwave myolysis is a feasible and effective procedure in a day surgery clinic
      for menorrhagia caused by submucosal myomas. The procedure may be an alternative
      to hysterectomy for menorrhagia caused by submucosal myomas in women during the
      perimenopausal period.

PMID- 26287992
TI  - An alternative theory to explain the effects of coalescing oil drops on
      mouthfeel.
AB  - In this letter, we demonstrate that through non-trivial rheological effects
      occurring in narrow gaps, it is possible to explain how coalescent oil drops
      contribute to the specific mouthfeel of such unstable emulsions. This theoretical
      framework allows us to get away from the commonly referred to lubrication
      argumentation and offers the advantage of being simple enough in terms of
      computation to be tested both numerically and sensorially using oils of different
      viscosities. We show that this interpretation allows us to account for around two
      orders of magnitude of apparent viscosity increase in such emulsions, when the
      coalescence is catastrophic (total). Such phenomena are predicted to have
      profound effects on the damping of the mechanical signal perceived by
      mechanoreceptors in the oral cavity and thus on mouthfeel perception. 

PMID- 26287994
TI  - Molecular identification of ascidians from the Palk Bay Region, Southeast coast
      of India.
AB  - BACKGROUND: More than 50 ascidian species distributed in the Palk Bay, Southeast
      coat of India. Up to a very few molecular work has been performed to determine
      the evolutionary relationships of ascidians in the world. OBJECTIVES: Present
      study explored the value of mtDNA data in assessing phylogenetic relationships
      within the family Ascidiacea, Didemnidae, Styelidae, and molecular identification
      of ascidians from the Palk Bay, Southeast coast of India. MATERIALS AND METHODS:
      The phylogeny analysis was executed based on mitochondrial cytochrome oxidase
      subunit I (COI) sequences of ascidian species. A BLASTN search can be run to
      determine the similarity of an unknown DNA sequence (query) with the collection
      of all known DNA sequences in GenBank. RESULT: The BLASTN results showed that
      Didemnum candidum, Ascidia ahodori and Styela clava match the other listings for
      these species in GenBank. Mitochondrial COI gene sequences of collected ascidians
      were submitted to GenBank and obtained the accession numbers. CONCLUSION: This
      study is the first report of molecular identification of ascidian species of the
      Palk Bay, Southeast coast of India. This information about Palk Bay ascidian
      communities provides a baseline of general biodiversity of that ecosystem.

PMID- 26287993
TI  - Optimization of a Pretargeted Strategy for the PET Imaging of Colorectal
      Carcinoma via the Modulation of Radioligand Pharmacokinetics.
AB  - Pretargeted PET imaging has emerged as an effective strategy for merging the
      exquisite selectivity of antibody-based targeting vectors with the rapid
      pharmacokinetics of radiolabeled small molecules. We previously reported the
      development of a strategy for the pretargeted PET imaging of colorectal cancer
      based on the bioorthogonal inverse electron demand Diels-Alder reaction between a
      tetrazine-bearing radioligand and a transcyclooctene-modified huA33
      immunoconjugate. Although this method effectively delineated tumor tissue, its
      clinical potential was limited by the somewhat sluggish clearance of the
      radioligand through the gastrointestinal tract. Herein, we report the development
      and in vivo validation of a pretargeted strategy for the PET imaging of
      colorectal carcinoma with dramatically improved pharmacokinetics. Two novel
      tetrazine constructs, Tz-PEG7-NOTA and Tz-SarAr, were synthesized, characterized,
      and radiolabeled with (64)Cu in high yield (>90%) and radiochemical purity
      (>99%). PET imaging and biodistribution experiments in healthy mice revealed that
      although (64)Cu-Tz-PEG7-NOTA is cleared via both the gastrointestinal and urinary
      tracts, (64)Cu-Tz-SarAr is rapidly excreted by the renal system alone. On this
      basis, (64)Cu-Tz-SarAr was selected for further in vivo evaluation. To this end,
      mice bearing A33 antigen-expressing SW1222 human colorectal carcinoma xenografts
      were administered huA33-TCO, and the immunoconjugate was given 24 h to accumulate
      at the tumor and clear from the blood, after which (64)Cu-Tz-SarAr was
      administered via intravenous tail vein injection. PET imaging and biodistribution
      experiments revealed specific uptake of the radiotracer in the tumor at early
      time points (5.6 +/- 0.7 %ID/g at 1 h p.i.), high tumor-to-background activity
      ratios, and rapid elimination of unclicked radioligand. Importantly, experiments
      with longer antibody accumulation intervals (48 and 120 h) yielded slight
      decreases in tumoral uptake but also concomitant increases in tumor-to-blood
      activity concentration ratios. This new strategy offers dosimetric benefits as
      well, yielding a total effective dose of 0.041 rem/mCi, far below the doses
      produced by directly labeled (64)Cu-NOTA-huA33 (0.133 rem/mCi) and (89)Zr-DFO
      huA33 (1.54 rem/mCi). Ultimately, this pretargeted PET imaging strategy boasts a
      dramatically improved pharmacokinetic profile compared to our first generation
      system and is capable of clearly delineating tumor tissue with high image
      contrast at only a fraction of the radiation dose created by directly labeled
      radioimmunoconjugates. 

PMID- 26287995
TI  - Ba-Wei-Di-Huang-Wan through its active ingredient loganin counteracts substance P
      enhanced NF-kappaB/ICAM-1 signaling in rats with bladder hyperactivity.
AB  - Overt bladder afferent activation may exacerbate endogenous substance P (SP)
      release to induce intercellular adhesion molecule-1 (ICAM-1)-mediated
      inflammation and reactive oxygen species (ROS) production leading to hyperactive
      bladder. Ba-Wei-Die-Huang-Wan (BWDHW), a traditional Chinese medicine, has been
      used to treat lower urinary tract symptoms in patients by undefined mechanisms.
      We explored the possible mechanisms and the active components of BWDHW on
      exogenous SP-induced bladder hyperactivity. BWDHW contained six major components:
      loganin, paeoniflorin, 5-hydroxymethylfurfural, cinnamic acid, cinnamaldehyde,
      and paeonol by high-performance liquid chromatography. In urethane-anesthetized
      female Wistar rats, we evaluated transcystometrogram, pelvic afferent nerve
      activity by electrophysiologic recording techniques, ICAM-1 expression by Western
      blot and immunohistochemistry, ROS amount by an ultrasensitive chemiluminescence
      method and possible ROS sources from the different leukocytes by specific stains
      in SP-treated bladder. BWDHW and its major component loganin dose-dependently
      inhibited H2 O2 and HOCl activity in vitro. Intragastrical BWDHW (250 mg/kg) and
      loganin (5 mg/kg) twice daily for 2 weeks did not affect the baseline micturition
      parameters. Intra-arterial SP (20 ug/rat) through neurokinin-1 receptor
      activation increased voiding frequency (shortened intercontraction intervals),
      pelvic afferent nerve activity, bladder NF-kappaB/ICAM-1 expression, bladder ROS
      amount, neutrophils adhesion to venous endothelium, CD68 (monocyte/macrophage),
      and mast cell infiltration in the inflamed bladder. BWDHW and loganin
      pretreatment significantly depressed SP-enhanced pelvic afferent nerve activity,
      bladder NF-kappaB/ICAM-1 expression, leukocyte infiltration, and ROS amount, and
      subsequently improved bladder hyperactivity. In conclusion, our results suggest
      that BWDHW and its active component loganin improves bladder hyperactivity via
      inhibiting SP/neurokinin-1 receptor signaling and depressing NF-kappaB/ICAM-1
      mediated oxidative injury and inflammation. Neurourol. Urodynam. 35:771-779,
      2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 26287996
TI  - Nest Success of Gunnison Sage-Grouse in Colorado, USA.
AB  - Gunnison Sage-Grouse (Centrocercus minimus) is a species of concern for which
      little demographic information exists. To help fill this information gap, we
      investigated factors affecting nest success in two populations of Gunnison Sage
      Grouse. We assessed the relative effects of (1) vegetation characteristics (e.g.,
      shrub height, shrub cover, grass cover, and grass height), (2) temporal factors
      (e.g., year, timing of incubation initiation, and nest age), (3) precipitation,
      and (4) age of the nesting female (yearling or adult) on nest success rates. We
      found 177 nests in the Gunnison Basin population (that contains 85-90% of the
      species) from 2005-2010 and 20 nests in the San Miguel population (that contains
      < 10% of the species) from 2007-2010. Temporal factors had the greatest impact on
      nest success compared to vegetation characteristics, precipitation, and female
      age. Nest success varied considerably among years ranging from 4.0%-60.2% in
      Gunnison Basin and from 12.9%- 51.9% in San Miguel. Nests that were initiated
      earlier in the breeding season had higher nest success (at least one egg
      hatches). Daily nest survival rates decreased during the course of incubation.
      None of the vegetation characteristics we examined were strongly related to nest
      success. 

PMID- 26287997
TI  - Infection of Bacterial Endosymbionts in Insects: A Comparative Study of Two
      Techniques viz PCR and FISH for Detection and Localization of Symbionts in
      Whitefly, Bemisia tabaci.
AB  - Bacterial endosymbionts have been associated with arthropods and large number of
      the insect species show interaction with such bacteria. Different approaches have
      been used to understand such symbiont- host interactions. The whitefly, Bemisia
      tabaci, a highly invasive agricultural pest, harbors as many as seven different
      bacterial endosymbionts. These bacterial endosymbionts are known to provide
      various nutritional, physiological, environmental and evolutionary benefits to
      its insect host. In this study, we have tried to compare two techniques,
      Polymerase chain reaction (PCR) and Flourescence in situ Hybridisation (FISH)
      commonly used for identification and localization of bacterial endosymbionts in
      B. tabaci as it harbors one of the highest numbers of endosymbionts which have
      helped it in becoming a successful global invasive agricultural pest. The
      amplified PCR products were observed as bands on agarose gel by electrophoresis
      while the FISH samples were mounted on slides and observed under confocal
      microscope. Analysis of results obtained by these two techniques revealed the
      advantages of FISH over PCR. On a short note, performing FISH, using LNA probes
      proved to be more sensitive and informative for identification as well as
      localization of bacterial endosymbionts in B. tabaci than relying on PCR. This
      study would help in designing more efficient experiments based on much reliable
      detection procedure and studying the role of endosymbionts in insects. 

PMID- 26287998
TI  - Is Mandatory Prospective Trial Registration Working to Prevent Publication of
      Unregistered Trials and Selective Outcome Reporting? An Observational Study of
      Five Psychiatry Journals That Mandate Prospective Clinical Trial Registration.
AB  - OBJECTIVE: To address the bias occurring in the medical literature associated
      with selective outcome reporting, in 2005, the International Committee of Medical
      Journal Editors (ICMJE) introduced mandatory trial registration guidelines and
      member journals required prospective registration of trials prior to patient
      enrolment as a condition of publication. No research has examined whether these
      guidelines are impacting psychiatry publications. Our objectives were to
      determine the extent to which articles published in psychiatry journals adhering
      to ICMJE guidelines were correctly prospectively registered, whether there was
      evidence of selective outcome reporting and changes to participant numbers, and
      whether there was a relationship between registration status and source of
      funding. MATERIALS AND METHODS: Any clinical trial (as defined by ICMJE)
      published between 1 January 2009 and 31 July 2013 in the top five psychiatry
      journals adhering to ICMJE guidelines (The American Journal of Psychiatry,
      Archives of General Psychiatry/JAMA Psychiatry, Biological Psychiatry, Journal of
      the American Academy of Child and Adolescent Psychiatry, and The Journal of
      Clinical Psychiatry) and conducted after July 2005 (or 2007 for two journals) was
      included. For each identified trial, where possible we extracted trial
      registration information, changes to POMs between publication and registry to
      assess selective outcome reporting, changes to participant numbers, and funding
      type. RESULTS: Out of 3305 articles, 181 studies were identified as clinical
      trials requiring registration: 21 (11.6%) were deemed unregistered, 61 (33.7%)
      were retrospectively registered, 37 (20.4%) had unclear POMs either in the
      article or the registry and 2 (1.1%) were registered in an inaccessible trial
      registry. Only 60 (33.1%) studies were prospectively registered with clearly
      defined POMs; 17 of these 60 (28.3%) showed evidence of selective outcome
      reporting and 16 (26.7%) demonstrated a change in participant numbers of 20% or
      more; only 26 (14.4%) of the 181 the trials were prospectively registered and did
      not alter their POMs or the time frames at which they were measured. Prospective
      registration with no changes in POMs occurred more frequently with pharmaceutical
      funding. DISCUSSION: Although standards are in place to improve prospective
      registration and transparency in clinical trials, less than 15% of psychiatry
      trials were prospectively registered with no changes in POMs. Most trials were
      either not prospectively registered, changed POMs or the timeframes at some point
      after registration or changed participant numbers. Authors, journal editors and
      reviewers need to further efforts to highlight the value of prospective trial
      registration.

PMID- 26288000
TI  - Hospital Admissions, Biological Therapy, and Surgery in Familial and Sporadic
      Cases of Inflammatory Bowel Disease: A Population-Based Cohort Study 1977-2011.
AB  - BACKGROUND: Easily accessible predictors of disease course in inflammatory bowel
      disease (IBD) are scarce, and it remains largely unknown whether a family history
      of IBD predicts the course of Crohn's disease (CD) and ulcerative colitis (UC).
      We aimed to compare the course of disease in familial and sporadic cases of IBD
      in a nationwide cohort study. METHODS: From national registries, covering a
      population of 8,295,773 individuals, we obtained information on date and year of
      diagnosis of IBD cases, gender, age, and family ties. Using Cox regression, we
      estimated hazard ratios for IBD-related hospitalization, biological treatment,
      and surgery in familial versus sporadic cases of IBD. RESULTS: A total of 27,886
      IBD cases, including 1006 IBD-relative pairs, were followed-up for up to 16
      years, totaling 164,979 person-years. We observed no difference in risk of
      hospital admissions between familial and sporadic cases of IBD. However, patients
      with familial CD had significantly higher risk of major surgery than sporadic CD
      cases after 2 years of disease duration (hazard ratio, 1.62; 95% confidence
      interval, 1.26-2.07). Also, sensitivity analysis suggested a slightly reduced
      time from diagnosis to first tumor necrosis factor-alpha inhibitor treatment
      among familial CD and UC cases as compared with sporadic cases. CONCLUSION: We
      found only minor differences in surgery rates and tumor necrosis factor exposure,
      between familial and sporadic cases of IBD. These findings may represent purely
      social rather than functional effects, which is consoling for newly diagnosed CD
      or UC patients with a family history of IBD.

PMID- 26287999
TI  - 1,25-Dihydroxyvitamin D Protects Intestinal Epithelial Barrier by Regulating the
      Myosin Light Chain Kinase Signaling Pathway.
AB  - BACKGROUND: The myosin light chain kinase (MLCK) pathway controls intestinal
      epithelial barrier permeability by regulating the tight junction. 1,25
      dihydroxyvitamin D (1,25(OH)2D3)-vitamin D receptor (VDR) signaling protects the
      epithelial barrier, but the molecular mechanism is incompletely understood.
      METHODS: MLCK activation and barrier permeability were studied using monolayers
      of HCT116, Caco-2, and SW480 cells treated with tissue necrosis factor alpha with
      or without 1,25(OH)2D3. The MLCK pathway was analyzed in normal and inflamed
      colonic biopsies from patients with ulcerative colitis. Colonic mucosal barrier
      permeability and MLCK activation were also investigated using trinitrobenzene
      sulfonic acid-induced colitis models in vitamin D analog paricalcitol-treated
      wild-type mice and mice carrying VDR deletion in colonic epithelial cells.
      RESULTS: Tissue necrosis factor alpha increased cell monolayer permeability and
      induced long isoform of MLCK expression and myosin II regulatory light chain
      (MLC) phosphorylation, and 1,25(OH)2D3 blocked tissue necrosis factor alpha
      induced increases in monolayer permeability and MLCK-MLC pathway activation by a
      VDR-dependent fashion. 1,25(OH)2D3 directly suppressed long MLCK expression by
      attenuating NF-kappaB activation, and chromatin immunoprecipitation assays
      confirmed that 1,25(OH)2D3 disrupted p65 binding to 3 kappaB sites in long MLCK
      gene promoter. In human ulcerative colitis biopsies, VDR reduction was associated
      with increases in long MLCK expression and MLC phosphorylation. In
      trinitrobenzene sulfonic acid colitis models, paricalcitol ameliorated colitis,
      attenuated the increase in mucosal barrier permeability, and inhibited long MLCK
      induction and MLC phosphorylation. In contrast, mice with colonic epithelial VDR
      deletion exhibited more robust increases in mucosal barrier permeability and MLCK
      activation compared with wild-type mice. CONCLUSIONS: These data demonstrate that
      1,25(OH)2D3-VDR signaling preserves the mucosal barrier integrity by abrogating
      MLCK-dependent tight junction dysregulation during colonic inflammation.

PMID- 26288001
TI  - Alterations of the Subgingival Microbiota in Pediatric Crohn's Disease Studied
      Longitudinally in Discovery and Validation Cohorts.
AB  - BACKGROUND: Oral manifestations are common in Crohn's disease (CD). Here we
      characterized the subgingival microbiota in pediatric patients with CD initiating
      therapy and after 8 weeks to identify microbial community features associated
      with CD and therapy. METHODS: Pediatric patients with CD were recruited from The
      Children's Hospital of Pennsylvania. Healthy control subjects were recruited from
      primary care or orthopedics clinic. Subgingival plaque samples were collected at
      initiation of therapy and after 8 weeks. Treatment exposures included 5-ASAs,
      immunomodulators, steroids, and infliximab. The microbiota was characterized by
      16S rRNA gene sequencing. The study was repeated in separate discovery (35 CD, 43
      healthy) and validation cohorts (43 CD, 31 healthy). RESULTS: Most subjects in
      both cohorts demonstrated clinical response after 8 weeks of therapy (discovery
      cohort 88%, validation cohort 79%). At week 0, both antibiotic exposure and
      disease state were associated with differences in bacterial community
      composition. Seventeen genera were identified in the discovery cohort as
      candidate biomarkers, of which 11 were confirmed in the validation cohort.
      Capnocytophaga, Rothia, and TM7 were more abundant in CD relative to healthy
      controls. Other bacteria were reduced in abundance with antibiotic exposure among
      CD subjects. CD-associated genera were not enriched compared with healthy
      controls after 8 weeks of therapy. CONCLUSIONS: Subgingival microbial community
      structure differed with CD and antibiotic use. Results in the discovery cohort
      were replicated in a separate validation cohort. Several potentially pathogenic
      bacterial lineages were associated with CD but were not diminished in abundance
      by antibiotic treatment, suggesting targets for additional surveillance.

PMID- 26288003
TI  - A New Type of Low Density Material: Shellular.
AB  - A new type of cellular material named Shellular, in which cells are composed of a
      continuous, smooth-curved shell according to the minimal surface theory, is
      proposed. Shellular specimens are fabricated using 3D lithography with negative
      templates and hard coating, and exhibit superb strength and stiffness at
      densities lower than 10(-2) Mg m(-3), incorporating benefits from hierarchical
      structures and constituent materials with nanosized grains.

PMID- 26288002
TI  - Efficacy of Vedolizumab as Induction Therapy in Refractory IBD Patients: A
      Multicenter Cohort.
AB  - BACKGROUND: Vedolizumab (VDZ) demonstrated efficacy in Crohn's disease (CD) and
      ulcerative colitis (UC) in the GEMINI trials. Our aim was to evaluate the
      efficacy of VDZ at week 14 in inflammatory bowel disease in a multicenter cohort
      of patients. METHODS: Patients at Massachusetts General Hospital and Brigham and
      Women's Hospital were considered for inclusion. VDZ (300 mg) was administered at
      weeks 0, 2, 6, and 14. Efficacy was assessed using the Harvey-Bradshaw index for
      CD, the simple clinical colitis activity index for UC and physician assessment,
      along with C-reactive protein and decrease of corticosteroid therapy. Clinical
      response was defined as decrease in Harvey-Bradshaw index >=3 and simple clinical
      colitis activity index >=3 and remission as Harvey-Bradshaw index <=4, simple
      clinical colitis activity index <=2 and physician assessment of response and
      remission. RESULTS: Our study included 172 patients (107 CD, 59 UC, 6
      inflammatory bowel disease-unclassified, men 48.3%, mean age 40 years and disease
      duration 14 years). Fourteen patients had ostomy and 9 ileoanal pouch, and only
      35.5% fulfilled eligibility for the GEMINI trials. Previous treatment failures
      with >= 2 anti-TNFs occurred in 70.9%, one-third were on an immunomodulator and
      46% systemic steroids at baseline. In CD, 48.9% and 23.9% and in UC, 53.9% and
      29.3% had clinical response and clinical remission at week 14, respectively.
      Adverse events occurred in 10.5%. CONCLUSIONS: VDZ is safe and well tolerated in
      refractory inflammatory bowel disease patients in a clinical practice with
      efficacy in UC and CD with responses similar to what was seen in clinical trials.

PMID- 26288004
TI  - Myoepithelial carcinoma of the extremity: Response to isolated limb infusion.
AB  - We report our experience with two patients with myoepithelial carcinoma (MEC) of
      the extremity. An 83-year-old male and a 35-year-old female were treated with
      standard isolated limb infusion (ILI), using melphalan and dactinomycin. The
      first patient had a complete response (CR) that was sustained for two and a half
      years, until he developed a regional lymph node metastasis. The second patient
      had a 4.7 cm tumor located on her left hand with metastasis to the ipsilateral
      axillary lymph nodes. Initial treatment consisted of ILI and left axillary
      lymphadenectomy. The primary tumor regressed and showed signs of central
      necrosis, measuring 2.8 cm after 1 month. Though she was continuing to respond, a
      decision was made by her orthopedic surgeon to administer neoadjuvant radiation
      followed by surgical resection.

PMID- 26288005
TI  - Comparison of US and Canadian Perioperative Outcomes and Hospital Efficiency
      After Total Hip and Knee Arthroplasty.
AB  - IMPORTANCE: The combination of an aging population, growing number of medical
      interventions, and surging economic burden of health care has renewed interest in
      reevaluating and exploring new health care models. OBJECTIVES: To compare the
      performance of the US and Canadian health care systems by assessing major
      complications following primary total hip arthroplasty (THA) and total knee
      arthroplasty (TKA) and to measure the efficiency of both health care models by
      comparing the postoperative length of stay. DESIGN, SETTING, AND PARTICIPANTS:
      With patients grouped according to the country where they underwent surgery, we
      queried the National Surgical Quality Improvement Program database to identify
      55,335 Canadian and US patients who underwent primary elective THA or TKA between
      January 1, 2011, and December 31, 2012. MAIN OUTCOMES AND MEASURES: Differences
      in patient demographics, as well as the rate of 30-day major complications and
      length of stay, were compared between patients hospitalized in the United States
      and Canada. RESULTS: Baseline characteristics were similar between the groups.
      Most US patients underwent general anesthesia (THA, 61.8%; TKA, 59.4%); Canadian
      patients received more regional anesthesia (THA, 78.7%; TKA, 81.0%). Patients in
      the United States received more transfusions postoperatively (THA, 9.0% more;
      TKA, 6.4% more; P < .001) and had shorter hospitalizations (THA, 1.4 days less;
      TKA, 1.3 days less; P < .001) with a greater proportion of patients discharged to
      rehabilitation facilities (THA, 21.6% more; TKA, 26.6% more; P < .001). With
      results reported as incidence rate ratios (95% CIs), after adjusting for all
      other variables, risk factors, and adverse outcomes, having surgery in Canada
      increased the postoperative length of stay by 57% (1.57 [1.53-1.61]) for THA and
      49% (1.49 [1.46-1.52]) for TKA. With results reported as odds ratios (95% CIs),
      major complications were significantly more common in Canada following TKA (1.65
      [1.31-2.07]) but not THA (1.09 [0.79-1.51]). CONCLUSIONS AND RELEVANCE: The rate
      of major complications was significantly higher in Canada following TKA, but
      there was no significant difference following THA. Patients undergoing the
      procedures in US hospitals also had substantially shorter lengths of hospital
      stay, perhaps reflecting more efficient postoperative care and discharge planning
      in those facilities.

PMID- 26288007
TI  - Selective Metal Exsolution in BaFe(2-y)M(y)(PO4)2 (M = Co(2+), Ni(2+)) Solid
      Solutions.
AB  - The 2D-Ising ferromagnetic phase BaFe(2+)2(PO4)2 shows exsolution of up to one
      third of its iron content (giving BaFe(3+)1.33(PO4)2) under mild oxidation
      conditions, leading to nanosized Fe2O3 exsolved clusters. Here we have prepared
      BaFe(2-y)M(y)(PO4)2 (M = Co(2+), Ni(2+); y = 0, 0.5, 1, 1.5) solid solutions to
      investigate the feasibility and selectivity of metal exsolution in these mixed
      metallic systems. For all the compounds, after 600  degrees C thermal treatment
      in air, a complete oxidation of Fe(2+) to Fe(3+) leaves stable M(2+) ions, as
      verified by (57)Fe Mossbauer spectroscopy, TGA, TEM, microprobe, and XANES. The
      size of the nanometric alpha-Fe2O3 clusters coating the main phase strongly
      depends on the yM metal concentration. For M-rich phases the iron diffusion is
      hampered so that a significant fraction of superparamagnetic alpha-Fe2O3
      particles (100% for BaFe(0.5-x)Co(1.5)(PO4)2) was detected even at 78 K. Although
      Ni(2+) and Co(2+) ions tend to block Fe diffusion, the crystal structure of
      BaFe(0.67)Co1(PO4)2 demonstrates a fully ordered rearrangement of Fe(3+) and
      Co(2+) ions after Fe exsolution. The magnetic behaviors of the Fe-depleted
      materials are mostly dominated by antiferromagnetic exchange, while Co(2+)-rich
      compounds show metamagnetic transitions reminiscent of the BaCo2(PO4)2 soft
      helicoidal magnet.

PMID- 26288006
TI  - Trophoblast retrieval and isolation from the cervix (TRIC) is unaffected by early
      gestational age or maternal obesity.
AB  - OBJECTIVE: The objective of this study is to evaluate whether trophoblast yield
      obtained by trophoblast retrieval and isolation from the cervix (TRIC) is
      affected by pregnancy outcome, gestational age (GA) at retrieval, maternal body
      mass index (BMI), parity, or maternal age. METHODS: TRIC was performed on 224
      ongoing pregnancies between 5 and 20 weeks of GA. Trophoblast cells were isolated
      from cervical cells using anti-human leukocyte antigen-G antibody coupled to
      magnetic nanoparticles. Purity was assessed by the percentage of isolated cells
      that express beta-hCG. Patient records were monitored until delivery, and
      pregnancy outcomes were determined. Trophoblast yield was compared with GA at
      time of collection, maternal BMI, parity, maternal age, and outcome of pregnancy,
      using linear regression. RESULTS: There was no effect of GA, maternal BMI,
      parity, and maternal age on trophoblast yield. Trophoblast yield decreased
      significantly with early pregnancy loss compared with uncomplicated pregnancies
      that delivered at term. Trophoblast yield with preeclampsia or intrauterine
      growth restriction was decreased compared with healthy term outcomes; however,
      they did not reach statistical significance. CONCLUSIONS: If TRIC becomes
      available as a method for non-invasive prenatal testing, our data demonstrate
      that it is unaffected by BMI and is useful as early as 5 weeks of GA.

PMID- 26288009
TI  - Patients are a virtue: advances in microengineered systems for clinical
      applications.
AB  - Microscale technologies have been widely used in modern biology over the last
      decade, and have promised to revolutionize life sciences and biomedicine.
      However, the majority of microdevices developed to date have largely remained in
      the laboratory, with only a small fraction being applied in the field or clinic
      where their true impact on human health is best evaluated. Recently, microscale
      technologies have seen a rise in usage in applications with a clinical focus,
      indicating growing interest in this research direction. Here, we highlight the
      latest developments in microscale technologies designed specifically to handle,
      interrogate, and analyze human clinical samples for diagnostics and other
      applications. 

PMID- 26288008
TI  - Chondroitin sulfate effects on neural stem cell differentiation.
AB  - We have investigated the role chondroitin sulfate has on cell interactions during
      neural plate formation in the early chick embryo. Using tissue culture isolates
      from the prospective neural plate, we have measured neural gene expression
      profiles associated with neural stem cell differentiation. Removal of chondroitin
      sulfate from stage 4 neural plate tissue leads to altered associations of N
      cadherin-positive neural progenitors and causes changes in the normal sequence of
      neural marker gene expression. Absence of chondroitin sulfate in the neural plate
      leads to reduced Sox2 expression and is accompanied by an increase in the
      expression of anterior markers of neural regionalization. Results obtained in
      this study suggest that the presence of chondroitin sulfate in the anterior chick
      embryo is instrumental in maintaining cells in the neural precursor state. 

PMID- 26288010
TI  - RAFT Polymerization of N-[3-(Trimethoxysilyl)-propyl]acrylamide and Its Versatile
      Use in Silica Hybrid Materials.
AB  - Reversible addition-fragmentation chain transfer (RAFT) polymerization and
      characterization of an alkoxysilane acrylamide monomer using a trithiocarbonate
      chain transfer agent are described. Poly(N-[3-(trimethoxysilyl)propyl]acrylamide)
      (PTMSPAA) homopolymers are obtained with good control over the polymerization. A
      linear increase in the molecular weight is observed whereas the polydispersity
      values do not exceed 1.2 regardless of the monomer conversion. Moreover, PTMSPAA
      is used as a macro-RAFT agent to polymerize N-isopropylacrylamide (NIPAM). By
      varying the degree of polymerization of NIPAM within the block copolymer,
      different sizes of thermoresponsive particles are obtained. These particles are
      stabilized by the condensation of the alkoxysilane moieties of the polymers.
      Furthermore, a co-network of silica and PTMSPAA is prepared using the sol-gel
      process. After drying, transparent mesoporous hybrids are obtained with a surface
      area of up to 400 m(2) g(-1).

PMID- 26288011
TI  - Phosphorus Accumulation and Sorption in Calcareous Soil under Long-Term
      Fertilization.
AB  - Application of phosphorus (P) fertilizers to P-deficient soils can also result in
      P accumulation. In this study, soil P status and P uptake by apple trees were
      investigated in 5-, 10-, and 15-year-old orchards in the semi-arid Loess Plateau,
      China, and subset soils with different soil P statuses (14-90 Olsen-P mg kg(-1))
      were selected to evaluate the characteristic P adsorption. Due to the low P-use
      efficiency (4-6%), total soil P increased from 540 mg kg(-1) to 904 mg kg(-1),
      Olsen-P ranged from 3.4 mg kg(-1) to 30.7 mg kg(-1), and CaCl2-P increased from
      less than 0.1 mg kg(-1) to 0.66 mg kg(-1) under continuous P fertilization. The P
      sorption isotherms for each apple orchard were found to fit the Langmuir isotherm
      model (R2 = 0.91-0.98). K (binding energy) and Qm (P sorption maximum) decreased,
      whereas DPS (degree of phosphorus sorption) increased with increasing P
      concentration. CaCl2-P increased significantly with the increase of Olsen-P,
      especially above the change point of 46.1 mg kg(-1). Application of surplus P
      could result in P enrichment in P-deficient soil which has high P fixation
      capacity, thus posing a significant environmental risk.

PMID- 26288012
TI  - Dietary Magnesium Is Positively Associated With Skeletal Muscle Power and Indices
      of Muscle Mass and May Attenuate the Association Between Circulating C-Reactive
      Protein and Muscle Mass in Women.
AB  - Age-related loss of skeletal muscle mass and strength are risk factors for
      sarcopenia, osteoporosis, falls, fractures, frailty, and mortality. Dietary
      magnesium (Mg) could play a role in prevention of age-related loss of skeletal
      muscle mass, power, and strength directly through physiological mechanisms or
      indirectly through an impact on chronic low-grade inflammation, itself a risk
      factor for loss of skeletal muscle mass and strength. In a cross-sectional study
      of 2570 women aged 18 to 79 years, we examined associations between intakes of
      Mg, estimated using a food-frequency questionnaire (FFQ), dual-energy X-ray
      absorptiometry (DXA)-derived measures of muscle mass (fat-free mass as a
      percentage of body weight [FFM%], fat-free mass index [FFMI, kg/m(2)]), leg
      explosive power (LEP), and grip strength (n = 949 only). We also examined
      associations between circulating hs-CRP (C-reactive protein) and muscle mass and
      LEP, and explored the potential attenuation of these relationships by Mg. We
      compared our findings with those of age and protein intake. Endpoints were
      calculated by quintile of Mg and adjusted for relevant confounders. Significant
      positive associations were found between a higher Mg and indices of skeletal
      muscle mass and LEP, and also with hs-CRP, after adjustment for covariates.
      Contrasting extreme quintiles of Mg intake showed differences of 2.6% for FFM% (p
      trend < 0.001), 0.4 kg/m(2) for FFMI (p trend = 0.005), and 19.6 watts/kg for LEP
      (p trend < 0.001). Compared with protein, these positive associations were 7
      times greater for FFM% and 2.5 times greater for LEP. We also found that higher
      hs-CRP was negatively associated with skeletal muscle mass and, in statistical
      modeling, that a higher dietary Mg attenuated this negative relationship by 6.5%,
      with greater attenuation in women older than 50 years. No association was found
      between Mg and grip strength. Our results suggest that dietary magnesium may aid
      conservation of age-related loss of skeletal muscle mass and power in women of
      all ages.

PMID- 26288014
TI  - The relationship between core symptoms of ADHD and the Cognitive Reflection Test
      in a non-clinical sample.
AB  - INTRODUCTION: Attention Deficit and Hyperactivity Disorder (ADHD) symptoms are
      frequently linked to executive function deficits. There is reason to believe that
      these deficits may give rise to problems with complex reasoning and problem
      solving. METHODS: Eighty-six men (N = 45) and women (N = 41) completed a self
      report measure to assess ADHD symptoms, along with a complex reasoning task; the
      Cognitive Reflection Test (CRT). IQ was also tested due to its covariance with
      reasoning ability. RESULTS: Analysis suggested that all three symptoms of ADHD
      (inattention, hyperactivity, and impulsivity) are negatively related to
      performance on the CRT, however, only inattention significantly contributed to a
      model that predicted CRT performance. CONCLUSIONS: Of the three core symptoms of
      ADHD, inattention is the most important for reasoning ability. Results are
      discussed with reference to an executive function model of ADHD, with particular
      emphasis on the role of working memory in inattention.

PMID- 26288013
TI  - Mesenchymal Stem Cells Stabilize Atherosclerotic Vulnerable Plaque by Anti
      Inflammatory Properties.
AB  - BACKGROUND AND OBJECTIVES: Formation and progression of atherosclerotic
      vulnerable plaque (VP) is the primary cause of many cardio-cerebrovascular
      diseases such as acute coronary syndrome and stroke. It has been reported that
      bone marrow mesenchymal stem cells (MSC) exhibit protective effects against many
      kinds of diseases including myocardial infarction. Here, we examined the effects
      of intravenous MSC infusion on a VP model and provide novel evidence of its
      influence as a therapy in this animal disease model. SUBJECTS AND METHODS: Thirty
      healthy male New Zealand white rabbits were randomly divided into a MSC, VP or
      stable plaque (SP) group (n = 10/group) and received high fat diet and cold
      induced common carotid artery intimal injury with liquid nitrogen to form
      atherosclerotic plaques. Serum hs-CRP, TNF-alpha, IL-6 and IL-10 levels were
      measured by ELISA at 1, 2, 3, 7, 14, 21 and 28 days after MSC transplantation.
      The animals were sacrificed at 4 weeks after MSC transplantation. Lesions in the
      right common carotid were observed using H&E and Masson staining, and the fibrous
      cap/lipid core ratio of atherosclerotic plaques were calculated. The expression
      of nuclear factor kappaB (NF-kappaB) and matrix metalloproteinase 1, 2, 9 (MMP
      1,2,9) in the plaque were detected using immunohistochemistry, and apoptotic
      cells in the plaques were detected by TUNEL. In addition, the level of TNF-alpha
      stimulated gene/protein 6 (TSG-6) mRNA and protein were measured by quantitative
      Real-Time PCR and Western blotting, respectively. RESULTS: Two rabbits in the VP
      group died of lung infection and cerebral infarction respectively at 1 week after
      plaque injury by liquid nitrogen. Both H&E and Masson staining revealed that the
      plaques from the SP and MSC groups had more stable morphological structure and a
      larger fibrous cap/lipid core ratio than the VP group. Serum hs-CRP, TNF-alpha
      and IL-6 were significantly down-regulated, whereas IL-10 was significantly up
      regulated in the MSC group compared with the VP group. .Immunohistochemistry
      analysis revealed that NF-kappaB and MMP expression was reduced in the MSC and SP
      groups compared to the VP group. Cell apoptosis decreased significantly in both
      the MSC and SP groups in comparison to the VP group. TSG-6 mRNA and protein
      expression were higher in the plaques of the MSC group compared to the VP and SP
      groups. CONCLUSIONS: Our study results suggest that MSC transplantation can
      effectively stabilize vulnerable plaques in atherosclerotic rabbits. This may
      potentially offer a new clinical application of MSC in atherosclerosis.

PMID- 26288015
TI  - Human Papillomavirus Type 18 cis-Elements Crucial for Segregation and Latency.
AB  - Stable maintenance replication is characteristic of the latency phase of HPV
      infection, during which the viral genomes are actively maintained as
      extrachromosomal genetic elements in infected proliferating basal keratinocytes.
      Active replication in the S-phase and segregation of the genome into daughter
      cells in mitosis are required for stable maintenance replication. Most of our
      knowledge about papillomavirus genome segregation has come from studies of bovine
      papillomavirus type 1 (BPV-1), which have demonstrated that the E2 protein
      cooperates with cellular trans-factors and that E2 binding sites act as cis
      regulatory elements in the viral genome that are essential for the segregation
      process. However, the genomic organization of the regulatory region in HPVs, and
      the properties of the viral proteins are different from those of their BPV-1
      counterparts. We have designed a segregation assay for HPV-18 and used it to
      demonstrate that the E2 protein performs segregation in combination with at least
      two E2 binding sites. The cooperative binding of the E2 protein to two E2 binding
      sites is a major determinant of HPV-18 genome segregation, as demonstrated by the
      change in spacing between adjacent binding sites #1 and #2 in the HPV-18 Upstream
      Regulatory Region (URR). Duplication or triplication of the natural 4 bp 5'-CGGG
      3' spacer between the E2 binding sites increased the cooperative binding of the
      E2 molecules as well as E2-dependent segregation. Removal of any spacing between
      these sites eliminated cooperative binding of the E2 protein and disabled
      segregation of the URR and HPV-18 genome. Transfer of these configurations of the
      E2 binding sites into viral genomes confirmed the role of the E2 protein and
      binding sites #1 and #2 in the segregation process. Additional analysis
      demonstrated that these sites also play an important role in the transcriptional
      regulation of viral gene expression from different HPV-18 promoters. 

PMID- 26288017
TI  - Why Is the Association of Phosphorus and FGF23 with Mortality Stronger in African
      American Hemodialysis Patients.

PMID- 26288018
TI  - All my relations: understanding the experiences of Native Americans with
      disabilities.

PMID- 26288016
TI  - Microglia Induce Neurotoxic IL-17+ gammadelta T Cells Dependent on TLR2, TLR4,
      and TLR9 Activation.
AB  - BACKGROUND: Interleukin-17 (IL-17) acts as a key regulator in central nervous
      system (CNS) inflammation. gammadelta T cells are an important innate source of
      IL-17. Both IL-17+ gammadelta T cells and microglia, the major resident immune
      cells of the brain, are involved in various CNS disorders such as multiple
      sclerosis and stroke. Also, activation of Toll-like receptor (TLR) signaling
      pathways contributes to CNS damage. However, the mechanisms underlying the
      regulation and interaction of these cellular and molecular components remain
      unclear. OBJECTIVE: In this study, we investigated the crosstalk between
      gammadelta T cells and microglia activated by TLRs in the context of neuronal
      damage. To this end, co-cultures of IL-17+ gammadelta T cells, neurons, and
      microglia were analyzed by immunocytochemistry, flow cytometry, ELISA and
      multiplex immunoassays. RESULTS: We report here that IL-17+ gammadelta T cells
      but not naive gammadelta T cells induce a dose- and time-dependent decrease of
      neuronal viability in vitro. While direct stimulation of gammadelta T cells with
      various TLR ligands did not result in up-regulation of CD69, CD25, or in IL-17
      secretion, supernatants of microglia stimulated by ligands specific for TLR2,
      TLR4, TLR7, or TLR9 induced activation of gammadelta T cells through IL-1beta and
      IL-23, as indicated by up-regulation of CD69 and CD25 and by secretion of vast
      amounts of IL-17. This effect was dependent on the TLR adaptor myeloid
      differentiation primary response gene 88 (MyD88) expressed by both gammadelta T
      cells and microglia, but did not require the expression of TLRs by gammadelta T
      cells. Similarly to cytokine-primed IL-17+ gammadelta T cells, IL-17+ gammadelta
      T cells induced by supernatants derived from TLR-activated microglia also caused
      neurotoxicity in vitro. While these neurotoxic effects required stimulation of
      TLR2, TLR4, or TLR9 in microglia, neuronal injury mediated by bone marrow-derived
      macrophages did not require TLR signaling. Neurotoxicity mediated by IL-17+
      gammadelta T cells required a direct cell-cell contact between T cells and
      neurons. CONCLUSION: Taken together, these results point to a crucial role for
      microglia activated through TLRs in polarization of gammadelta T cells towards
      neurotoxic IL-17+ gammadelta T cells.

PMID- 26288019
TI  - Study of the Histology of Leafy Axes and Male Cones of Glenrosa carentonensis sp.
      nov. (Cenomanian Flints of Charente-Maritime, France) Using Synchrotron
      Microtomography Linked with Palaeoecology.
AB  - We report exceptionally well-preserved plant remains ascribed to the extinct
      conifer Glenrosa J. Watson et H.L. Fisher emend. V. Srinivasan inside silica-rich
      nodules from the Cenomanian of the Font-de-Benon quarry, Charente-Maritime,
      western France. Remains are preserved in three dimensions and mainly consist of
      fragmented leafy axes. Pollen cones of this conifer are for the first time
      reported and in some cases remain connected to leafy stems. Histology of Glenrosa
      has not previously been observed; here, most of internal tissues and cells are
      well-preserved and allow us to describe a new species, Glenrosa carentonensis sp.
      nov., using propagation phase-contrast X-ray synchrotron microtomography, a non
      destructive technique. Leafy axes consist of characteristic helically arranged
      leaves bearing stomatal crypts. Glenrosa carentonensis sp. nov. differs from the
      other described species in developing a phyllotaxy 8/21, claw-shaped leaves, a
      thicker cuticle, a higher number of papillae and stomata per crypt. Pollen cones
      consist of peltate, helically arranged microsporophylls, each of them bearing 6-7
      pollen sacs. The new high resolution tomographic approach tested here allows
      virtual palaeohistology on plants included inside a dense rock to be made. Most
      tissues of Glenrosa carentonensis sp. nov. are described. Lithological and
      palaeontological data combined with xerophytic features of Glenrosa carentonensis
      sp. nov. suggest that this conifer has been adapted to survive in harsh and
      instable environments such as coastal area exposed to hot, dry conditions. 

PMID- 26288020
TI  - Impact of Cardiopulmonary Bypass on Respiratory Mucociliary Function in an
      Experimental Porcine Model.
AB  - BACKGROUND: The impact of cardiac surgery using cardiopulmonary bypass (CPB) on
      the respiratory mucociliary function is unknown. This study evaluated the effects
      of CPB and interruption of mechanical ventilation on the respiratory mucociliary
      system. METHODS: Twenty-two pigs were randomly assigned to the control (n = 10)
      or CPB group (n = 12). After the induction of anesthesia, a tracheostomy was
      performed, and tracheal tissue samples were excised (T0) from both groups. All
      animals underwent thoracotomy. In the CPB group, an aorto-bicaval CPB was
      installed and maintained for 90 minutes. During the CPB, mechanical ventilation
      was interrupted, and the tracheal tube was disconnected. A second tracheal tissue
      sample was obtained 180 minutes after the tracheostomy (T180). Mucus samples were
      collected from the trachea using a bronchoscope at T0, T90 and T180. Ciliary beat
      frequency (CBF) and in situ mucociliary transport (MCT) were studied in ex vivo
      tracheal epithelium. Mucus viscosity (MV) was assessed using a cone-plate
      viscometer. Qualitative tracheal histological analysis was performed at T180
      tissue samples. RESULTS: CBF decreased in the CPB group (13.1 +/- 1.9 Hz vs. 11.1
      +/- 2.1 Hz, p < 0.05) but not in the control group (13.1 +/- 1 Hz vs. 13 +/- 2.9
      Hz). At T90, viscosity was increased in the CPB group compared to the control (p
      < 0.05). No significant differences were observed in in situ MCT. Tracheal
      histology in the CPB group showed areas of ciliated epithelium loss, submucosal
      edema and infiltration of inflammatory cells. CONCLUSION: CPB acutely contributed
      to alterations in tracheal mucocilliary function.

PMID- 26288021
TI  - The Surgeon's Contribution to Image-Guided Oncology.
AB  - BACKGROUND: Advances in surgical and in imaging technology permit the performance
      of complex tumour resections in a safe and oncologically correct manner. To date,
      this has mainly implicated refined preoperative imaging methods, such as three
      dimensional computer-assisted planning (3D-CASP). With the advent of modern
      hybrid operating rooms, intraoperative imaging has spread and various techniques
      of intraoperative image guidance have been developed. METHODS: We review recent
      advances in intraoperative image guidance. We also delineate the role of
      intraoperative imaging techniques such as intraoperative ultrasound and computed
      tomography for real-time image guidance in laparoscopic liver surgery. RESULTS:
      Our review shows that advances in intraoperative imaging accompany the increasing
      use of laparoscopic approaches in visceral surgery. For the liver surgeon working
      laparoscopically, the loss of tactile sensation and the complex three-dimensional
      anatomy of the human liver make 3D-imaging techniques and intraoperative image
      guidance indispensable. We describe the role of 3D-CASP in preoperative surgical
      planning in liver surgery. CONCLUSION: An innovative imaging strategy for
      identifying liver segments during laparoscopic liver surgery by applying a
      fluorescent imaging method is proposed.

PMID- 26288022
TI  - Subjective sleep quality and postconcussion symptoms following mild traumatic
      brain injury.
AB  - PRIMARY OBJECTIVE: The goal of this investigation is to examine the prevalence of
      poor subjective sleep in patients with a history of mild traumatic brain injury
      (mTBI) and examine the relationship between subjective sleep quality and
      postconcussive symptoms (PCS), above and beyond the typical demographic and
      psychological distress variables. RESEARCH DESIGN: Individuals with a history of
      mTBI completed online questionnaires. Regression analysis was utilized to
      determine if subjective sleep quality would predict PCS severity, above and
      beyond demographic variables and psychological distress. METHODS AND PROCEDURES:
      Individuals with a history of mTBI (n = 158) completed surveys online. Sleep
      quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) and PCS with
      the Neurobehavioral Symptom Inventory (NSI). Demographic information was
      collected and psychological distress was measured using the Brief Symptom
      Inventory-18 (BSI-18). MAIN OUTCOMES AND RESULTS: In this sample, 92% of patients
      with mTBI reported poor sleep. Sleep quality significantly accounted for the
      variance in PCS, above and beyond demographics, time since injury and
      psychological distress (p < 0.001), although only a small amount of the variance
      in PCS was explained. CONCLUSIONS: Results indicate that poor subjective sleep
      quality is a significant problem in those with mTBI. While sleep is associated
      with PCS severity, psychological distress is a more potent predictor.

PMID- 26288024
TI  - Three new iridoids from two Viburnum species.
AB  - Three new iridoids, 10-deacetyl suspensolide A aglycone (1), 7-deacetyl
      suspensolide A aglycone (2), and 7,10-dideacetyl suspensolide A aglycone (3),
      were isolated from two species of Viburnum. Their structures were elucidated on
      the basis of spectroscopic methods, including 1D and 2D NMR techniques. Compound
      2 exhibited moderate anti-inflammatory activity against NO production in LPS
      stimulated RAW 264.7 cells with IC50 of 17.2 MUM. 

PMID- 26288025
TI  - Remogliflozin etabonate: a novel SGLT2 inhibitor for treatment of diabetes
      mellitus.
AB  - INTRODUCTION: Inhibitors of sodium-glucose co-transporter type 2 (SGLT2)
      represent a new class of anti-hyperglycemic agents with a unique mechanism of
      action. These drugs lower blood glucose by increasing urinary glucose excretion.
      Remogliflozin etabonate (RE) is a prodrug of remogliflozin, an SGLT2 inhibitor
      under development. AREAS COVERED: The following article reviews all of the
      clinical studies published regarding metabolism, drug interaction, safety and
      efficacy of RE in healthy subjects, patients with type 1 and type 2 diabetes.
      EXPERT OPINION: Available data suggest low potential for RE to interact with
      other drugs affecting the P450 system. Compared with placebo, RE reduces
      hemoglobin A1c (HbA1c) levels by an average of 0.5 - 1.0% after 12 weeks of
      therapy in drug-naive patients with type 2 diabetes. Because of its relatively
      short half-life, RE may be slightly more effective when used twice daily than
      once daily. One preliminary study also showed that RE decreased plasma glucose
      levels in type 1 diabetes. Advantages of RE include modest weight loss of ~ 2 kg,
      low risk of hypoglycemia, and a trend toward decrease in blood pressure. The
      commonest adverse effects of RE are genital mycotic infections, urinary tract
      infections, and dizziness. However, further studies are needed to establish its
      long-term safety and efficacy, and to determine whether it has specific
      advantages over currently approved SGLT2 inhibitors.

PMID- 26288023
TI  - Resilience, health, and quality of life among long-term survivors of
      hematopoietic cell transplantation.
AB  - BACKGROUND: Low patient-reported resilience is associated with an ongoing risk of
      poor health and psychosocial outcomes. Using a large cross-sectional sample of
      survivors of hematopoietic cell transplantation (HCT), this study explored
      associations between patient-reported resilience, psychological distress,
      posttraumatic growth, and health-related quality of life. METHODS: Between July
      1, 2013 and June 30, 2014, the annual Fred Hutchinson Cancer Research Center
      (FHCRC) posttransplant survivorship survey queried patient-reported health and
      functional status and included instruments assessing psychosocial outcomes: the
      10-item Connor-Davidson Resilience Scale, the Posttraumatic Growth Inventory, the
      Cancer and Treatment Distress measure, and the 12-item Medical Outcomes Study
      Short Form quality-of-life scale. Multivariate linear and logistic regression
      models included demographic and health covariates extracted from the FHCRC
      research database. RESULTS: Among 4643 adult survivors of HCT, 1823 (39%)
      responded after a single mailing and subsequent reminder letter. The
      participants' median age was 59 years (interquartile range [IQR], 50-66 years);
      52.5% were male, and most were non-Hispanic white. The median time since HCT was
      9 years (IQR, 3-18 years). Lower patient-reported resilience was associated with
      chronic graft-versus-host disease of higher severity, lower performance scores,
      missing work because of health, and permanent disability (all P < .0001). After
      adjustments for demographic and health characteristics, patients reporting low
      resilience scores had higher odds of having psychological distress (odds ratio
      [OR], 3.0; 95% confidence interval [CI], 2.1-4.3) and being in the lowest
      quartile for mental health-related quality of life (OR, 5.9; 95% CI, 4.4-8.0).
      CONCLUSIONS: Patient-reported resilience is independently associated with health
      and psychosocial outcomes. Future studies must determine whether interventions
      can bolster resilience and improve survivorship outcomes.

PMID- 26288027
TI  - The Preference to Discuss Expected Survival Is Associated with Loss of Meaning
      and Purpose in Terminally Ill Cancer Patients.
AB  - BACKGROUND: Demoralization is a syndrome of existential distress characterized by
      loss of meaning and purpose in life, hopelessness, and helplessness. Empirical
      data on its occurrence and associated factors in terminally ill patients is
      limited. OBJECTIVE: The study objective was to determine the frequency of
      demoralization and its association with individual and disease-related
      characteristics and to analyze the association between demoralization and the
      preference to discuss expected survival. METHODS: We recruited N = 55 terminally
      ill cancer patients (54% women, mean age 67 years) within 48 hours after
      admission to a specialized palliative care inpatient ward (55% had a Karnofsky
      performance status of <=50). Patients completed the Demoralization Scale (DS),
      the Generalized Anxiety Disorder Scale-7 (GAD-7), the Patient Health
      Questionnaire-9 (PHQ-9), and a single-item question measuring preferences for
      discussion of expected survival with a physician. RESULTS: We found clinically
      significant demoralization present in 19% and moderate demoralization present in
      10% of participants. Better educated patients reported a higher level of
      demoralization (d = 0.74, p = .010). Patients with a preference to discuss
      expected survival reported higher levels in the "loss of meaning and purpose"
      dimension of demoralization (d = 0.76, p = .010) and higher levels of anxiety (d
      = 0.88, p = .003) compared to those not wanting to discuss survival. CONCLUSIONS:
      Demoralization is a significant dimension of distress in terminally ill cancer
      patients. In the end-of-life inpatient care setting, the preference to discuss
      expected survival with a physician can parallel existential distress and anxiety.
      Further elucidation of patients' underlying existential needs will inform
      interventions that sustain meaning and hope in face of a limited life expectancy.

PMID- 26288026
TI  - Protective effect of pomegranate seed oil against cisplatin-induced
      nephrotoxicity in rat.
AB  - PURPOSE: Clinical use of cisplatin is limited by its nephrotoxicity. Cisplatin
      induced nephrotoxicity is associated with an increase in oxidative stress,
      leading ultimately to kidney dysfunction. The aim of this study was to
      investigate the effect of pomegranate seed oil against nephrotoxicity induced by
      cisplatin in adult rats. METHODS: Animals were divided into four groups. Group I
      received corn oil (1 mL/kg). Group II received cisplatin (8 mg/kg). Group III and
      IV received pomegranate seed oil (PSO) 0.4 mL/kg and 0.8 mL/kg one hour before
      cisplatin injection for 3 days, respectively. Blood samples were collected by
      cardiac puncture and used for measuring urea and creatinine concentration. Twenty
      hour urine samples were collected to measure protein and glucose concentration.
      The right kidney fixed in formalin for histological examination and the left
      kidney was homogenized for measurement of malondialdehyde and total sulfhydryl
      groups. RESULTS: A significant elevation of serum creatinine, urea, urinary
      glucose, protein concentrations, and non-significant decrease in total thiol
      content and increase in MDA level in kidney homogenates were observed in
      cisplatin-treated rats. Also cisplatin reduced animal's body weight. Mild-to
      moderate tubular cell necrosis, hyaline casts, and vascular congestion were
      observed in group II. PSO pre-treatment significantly decreased urinary protein,
      glucose, and serum creatinine concentration. PSO also caused a decrease in serum
      urea, renal MDA, and increase in thiol content, but the level of these parameters
      were not significant. CONCLUSION: The present results suggest that PSO is an
      effective agent for the prevention of cisplatin-induced renal dysfunction and
      oxidative damage in rat.

PMID- 26288028
TI  - A new basal sauropod from the pre-Toarcian Jurassic of South Africa: evidence of
      niche-partitioning at the sauropodomorph-sauropod boundary?
AB  - The early evolution of sauropod dinosaurs remains poorly understood, with a
      paucity of unequivocal sauropod taxa known from the first twenty million years of
      the Jurassic. Recently, the Early Jurassic of South Africa has yielded an
      assemblage of dental and post-cranial remains displaying a more apomorphic
      character suite than any other similarly aged sauropodomorph. These remains are
      interpreted as a new species of basal sauropod and recovered cladistically as the
      sister taxon to Vulcanodon +more derived Sauropoda, underscoring its importance
      for our understanding of this pivotal period of sauropod evolution. Key changes
      in the dentition, axial skeleton and forelimb of this new species suggest a
      genuine functional distinction occurring at the sauropodiform-sauropod boundary.
      With reference to these changes, we propose a scenario in which interdependent
      refinements of the locomotory and feeding apparatus occurred in tandem with, or
      were effected by, restrictions in the amount of vertical forage initially
      available to the earliest sauropods. The hypothesized instance of niche
      partitioning between basal sauropodan taxa and higher-browsing non-sauropodan
      sauropodomorphs may partially explain the rarity of true sauropods in the basal
      rocks of the Jurassic, while having the added corollary of couching the origins
      of Sauropoda in terms of an ecologically delimited 'event'. 

PMID- 26288029
TI  - Detection of gene-gene interactions using multistage sparse and low-rank
      regression.
AB  - Finding an efficient and computationally feasible approach to deal with the curse
      of high-dimensionality is a daunting challenge faced by modern biological
      science. The problem becomes even more severe when the interactions are the
      research focus. To improve the performance of statistical analyses, we propose a
      sparse and low-rank (SLR) screening based on the combination of a low-rank
      interaction model and the Lasso screening. SLR models the interaction effects
      using a low-rank matrix to achieve parsimonious parametrization. The low-rank
      model increases the efficiency of statistical inference and, hence, SLR screening
      is able to more accurately detect gene-gene interactions than conventional
      methods. Incorporation of SLR screening into the Screen-and-Clean approach
      (Wasserman and Roeder, 2009; Wu et al., 2010) is also discussed, which suffers
      less penalty from Boferroni correction, and is able to assign p-values for the
      identified variables in high-dimensional model. We apply the proposed screening
      procedure to the Warfarin dosage study and the CoLaus study. The results suggest
      that the new procedure can identify main and interaction effects that would have
      been omitted by conventional screening methods. 

PMID- 26288032
TI  - Self-reported physician-diagnosed asthma among Swedish adolescent, adult and
      former elite endurance athletes.
AB  - OBJECTIVE: Asthma is common among elite endurance athletes. Since the first
      published Swedish studies in 1993, awareness of "skiers' asthma" has increased.
      The current prevalence of asthma among Swedish skiers is unknown. This paper aims
      to present the design of a 5-year prospective annual questionnaire study on
      asthma among Swedish current and former elite endurance athletes, the first cross
      sectional results on prevalence, age of onset, and predictors of self-reported
      physician-diagnosed asthma in the study population. METHODS: An annual postal
      questionnaire is sent to Swedish elite skiers and orienteers during 2011-2015. In
      2013, former Swedish Olympic skiers were similarly invited. We present cross
      sectional data obtained in 2011 from the adolescents and adults and in 2013 from
      former skiers. A total of 491 athletes were invited. The results are presented by
      age, sex and sport. Chi-square test was used for group comparisons. Predictors of
      asthma were identified using logistic regression. RESULTS: Response rate was 82%.
      Among athletes aged 15-19, 29% of the skiers (38% of the female skiers), and 17%
      of the orienteers reported asthma (p = 0.071). Among the athletes aged 20-34, 35%
      of the skiers and 16% of the orienteers reported asthma (p = 0.029). Among the
      former skiers aged 40-94, 22% reported asthma. Among the active athletes, the
      onset of asthma was in early adolescence. Logistic regression found increasing
      age, female sex, allergy, family history of allergy/asthma and being skier
      predictors of self-reported physician-diagnosed asthma. CONCLUSIONS: The
      prevalence of physician-diagnosed asthma is high among Swedish endurance
      athletes, especially female adolescent skiers.

PMID- 26288033
TI  - Global statistics are not neglected.
AB  - In the framework of Reverse Hierarchy Theory it was suggested that initial vision
      at a glance brings the gist of the scene to conscious perception using explicit
      high cortical level representations, which are initially built by implicit bottom
      up processing (Hochstein & Ahissar, 2002). Only later return to lower cortical
      level representations introduces local details to conscious perception. Global
      statistics of similar elements are perceived rapidly and accurately, suggesting
      they are included in the initial perception of the gist of the scene, not
      depending on prior conscious perception of local details. Patients with
      unilateral spatial neglect have difficulty responding to elements in their
      contralesional hemifield. However, this deficit is especially pronounced for
      tasks that require focused attention, i.e., are dependent on the reverse
      hierarchy return. We review recent studies that indicate that perception of
      global statistics is among the spread attention tasks that are somewhat spared
      from this deficit. Combining these results, we suggest that perhaps the function
      of global statistics perception might include serving as a basic percept required
      for finding salient deviants from the mean, as in rapid odd element feature
      search paradigms, and perhaps subsequently focusing attention to them. 

PMID- 26288031
TI  - Repeat pregnancy in women with HIV infection in Latin America and the Caribbean.
AB  - Intended and unintended pregnancies occur frequently among human immunodeficiency
      virus (HIV)-infected women. We evaluated the occurrence of repeat pregnancy and
      characteristics associated with this outcome among HIV-infected women in Latin
      America and the Caribbean who were participating in the National Institute of
      Child Health and Human Development (NICHD) International Site Development
      Initiative (NISDI). Of the 1342 HIV-infected pregnant women enrolled in NISDI,
      124 (9.2%) had one or more repeat pregnancies on study. Median time between the
      index delivery and date of conception of the subsequent pregnancy was 1.4 years
      (range 0.1-5.7). Younger age (odds ratio [OR] = 1.07, 95% confidence interval
      [CI]: 1.04-1.11 per one year decrease in age), hospitalization during the index
      pregnancy or up to six months post-partum [OR = 2.0, 95% CI: 1.2-3.4], and poor
      index pregnancy outcome (stillbirth or spontaneous/therapeutic abortion; OR =
      3.4, 95% CI: 1.4-8.4) were associated with increased occurrence of repeat
      pregnancy in multivariable analysis. Among women with repeat pregnancies, the
      proportion receiving antiretroviral treatment (vs. prophylaxis) increased from
      39.4% at the time of the index pregnancy to 81.8% at the time of the repeat
      pregnancy (p < 0.001). These results can help identify women most likely to
      benefit from reproductive counseling in order to assist with healthy pregnancy
      planning and prevention of unintended pregnancies. 

PMID- 26288034
TI  - The Second ASRA Practice Advisory on Neurologic Complications Associated With
      Regional Anesthesia and Pain Medicine: Executive Summary 2015.
AB  - Neurologic injury associated with regional anesthetic or pain medicine procedures
      is extremely rare. The Second American Society of Regional Anesthesia and Pain
      Medicine Practice Advisory on Neurologic Complications Associated With Regional
      Anesthesia and Pain Medicine focuses on those complications associated with
      mechanical, ischemic, or neurotoxic injury of the neuraxis or peripheral nervous
      system. As with the first advisory, this iteration does not focus on hemorrhagic
      or infectious complications or local anesthetic systemic toxicity, all of which
      are the subjects of separate practice advisories. The current advisory offers
      recommendations to aid in the understanding and potential limitation of rare
      neurologic complications that may arise during the practice of regional
      anesthesia and/or interventional pain medicine. WHAT'S NEW: The Second American
      Society of Regional Anesthesia and Pain Medicine Practice Advisory on Neurologic
      Complications Associated With Regional Anesthesia and Pain Medicine updates
      information that was originally presented at the Society's first open forum on
      this subject (2005) and published in 2008. Portions of the second advisory were
      presented in an open forum (2012) and are herein updated, with attention to those
      topics subject to evolving knowledge since the first and second advisory
      conferences. The second advisory briefly summarizes recommendations that have not
      changed substantially. New to this iteration of the advisory is information
      related to the risk of nerve injury inherent to common orthopedic surgical
      procedures. Recommendations are expanded regarding the preventive role of various
      monitoring technologies such as ultrasound guidance and injection pressure
      monitoring. New clinical recommendations focus on emerging concerns including
      spinal stenosis and vertebral canal pathologies, blood pressure management during
      neuraxial anesthesia, administering blocks in anesthetized or deeply sedated
      patients, patients with preexisting neurologic disease, and inflammatory
      neuropathies. An updated diagnostic and treatment algorithm is presented.

PMID- 26288035
TI  - Comparing Postoperative Outcomes for Epidural Versus Intravenous Patient
      Controlled Analgesia.

PMID- 26288036
TI  - Cost Savings of Patient-Controlled Intrathecal Analgesia.

PMID- 26288037
TI  - Acupuncture for Pain Relief After Total Knee Arthroplasty: A Call for
      Clarification.

PMID- 26288038
TI  - p-Type Dye-Sensitized Solar Cells Based on Delafossite CuGaO2 Nanoplates with
      Saturation Photovoltages Exceeding 460 mV.
AB  - Exploring new p-type semiconductor nanoparticles alternative to the commonly used
      NiO is crucial for p-type dye-sensitized solar cells (p-DSSCs) to achieve higher
      open-circuit voltages (Voc). Here we report the first application of delafossite
      CuGaO2 nanoplates for p-DSSCs with high photovoltages. In contrast to the dark
      color of NiO, our CuGaO2 nanoplates are white. Therefore, the porous films made
      of these nanoplates barely compete with the dye sensitizers for visible light
      absorption. This presents an attractive advantage over the NiO films commonly
      used in p-DSSCs. We have measured the dependence of Voc on the illumination
      intensity to estimate the maximum obtainable Voc from the CuGaO2-based p-DSSCs.
      Excitingly, a saturation photovoltage of 464 mV has been observed when a
      polypyridyl Co(3+/2+)(dtb-bpy) electrolyte was used. Under 1 Sun AM 1.5
      illumination, a Voc of 357 mV has been achieved. These are among the highest
      values that have been reported for p-DSSCs. 

PMID- 26288039
TI  - Stacking Orientation Mediation of Pentacene and Derivatives for High Open-Circuit
      Voltage Organic Solar Cells.
AB  - In this Letter, we investigated the effect of the molecular stacking orientation
      on the open circuit voltage (VOC) of pentacene-based organic solar cells. Two
      functionalized pentacenes, namely, 6,13-diphenyl-pentacene (DP-penta) and 6,13
      dibiphenyl-4-yl-pentacene (DB-penta), were utilized. Different molecular stacking
      orientations of the pentacene derivatives from the pristine pentacene were
      identified by angle-dependent near-edge X-ray absorption fine structure
      measurements. It is concluded that pentacene molecules stand up on the substrate
      surface, while both functionalized pentacenes lie down. A significant increase of
      the VOC from 0.28 to 0.83 V can be achieved upon the utilization of
      functionalized pentacene, owing to the modulation of molecular stacking
      orientation, which induced a vacuum-level shift. 

PMID- 26288040
TI  - Density Functional Theory Study of the Interaction of Hydrogen with Li6C60.
AB  - Hydrogen storage properties of Li-coated C60 fullerene have been studied using
      density functional theory within the local density as well as generalized
      gradient approximation. Hydrogen atoms are found to bind to Li6C60 in two
      distinct forms, with the first set attaching to C atoms, not linked to Li, in
      atomic form. Once all such C atoms are saturated with hydrogen, the second set of
      hydrogen atoms bind quasi-molecularly to the Li atoms, five of which remain in
      the exohedral and the sixth in the endohedral position. The corresponding
      hydrogen gravimetric density in Li6C60H40 is 5 wt %. Desorption of hydrogen takes
      place in succession, the ones bound quasi-molecularly desorbing at a temperature
      lower than the ones bound atomically. The results are compared with the recent
      experiment on hydrogen adsorption in Li6C60. 

PMID- 26288042
TI  - Effects of Lattice Strain and Band Offset on Electron Transfer Rates in Type-II
      Nanorod Heterostructures.
AB  - Type-II nanorod heterostructures (NRHs) exhibit efficient directional charge
      separation and provide the potential to control this flow of charges through
      changes in structure and composition. We use transient-absorption spectroscopy to
      investigate how the magnitude of band offset and lattice strain alters dynamics
      of photogenerated electrons in CdSe/CdTe type-II NRHs. In the absence of alloying
      and strain effects, electron transfer occurs in ~300 fs. Reducing the conduction
      band offset by means of alloying leads to an even shorter charge-separation time
      (<200 fs), whereas curved NRHs with pronounced strain exhibit a longer charge
      separation time of ~700 fs. 

PMID- 26288041
TI  - Raman Spectroscopy of Oxide-Embedded and Ligand-Stabilized Silicon Nanocrystals.
AB  - Oxide-embedded and oxide-free alkyl-terminated silicon (Si) nanocrystals with
      diameters ranging from 3 nm to greater than 10 nm were studied by Raman
      spectroscopy. For ligand-passivated nanocrystals, the zone center Raman-active
      mode of diamond cubic Si shifted to lower frequency with decreasing size,
      accompanied by asymmetric peak broadening, as extensively reported in the
      literature. The size dependence of the Raman peak shifts, however, was
      significantly more pronounced than previously reported or predicted by the RWL
      (Richter, Wang, and Ley) and bond polarizability models. In contrast, Raman peak
      shifts for oxide-embedded nanocrystals were significantly less pronounced as a
      result of the stress induced by the matrix. 

PMID- 26288043
TI  - Isomer-Specific IR-IR Double Resonance Spectroscopy of D2-Tagged Protonated
      Dipeptides Prepared in a Cryogenic Ion Trap.
AB  - Isomer-specific vibrational predissociation spectra are reported for the gas
      phase GlySarH(+) and SarSarH(+) [Gly = glycine; Sar = sarcosine] ions prepared by
      electrospray ionization and tagged with weakly bound D2 adducts using a cryogenic
      ion trap. The contributions of individual isomers to the overlapping vibrational
      band patterns are completely isolated using a pump-probe photochemical hole
      burning scheme involving two tunable infrared lasers and two stages of mass
      selection (hence IR(2)MS(2)). These patterns are then assigned by comparison with
      harmonic (MP2/6-311+G(d,p)) spectra for various possible conformers. Both systems
      occur in two conformations based on cis and trans configurations with respect to
      the amide bond. In addition to the usual single intramolecular hydrogen bond
      motif between the protonated amine and the nearby amide oxygen atom, cis
      SarSarH(+) adopts a previous unreported conformation in which both amino NH's act
      as H-bond donors. The correlated red shifts in the NH donor and C?O acceptor
      components of the NH...O?C linkage to the acid group are unambiguously assigned
      in the double H-bonded conformer. 

PMID- 26288044
TI  - Stability of Porous Platinum Nanoparticles: Combined In Situ TEM and Theoretical
      Study.
AB  - Porous platinum nanoparticles provide a route for the development of catalysts
      that use less platinum without sacrificing catalytic performance. Here, we
      examine porous platinum nanoparticles using a combination of in situ transmission
      electron microscopy and calculations based on a first-principles-parametrized
      thermodynamic model. Our experimental observations show that the initially
      irregular morphologies of the as-sythesized porous nanoparticles undergo changes
      at high temperatures to morphologies having faceted external surfaces with voids
      present in the interior of the particles. The increasing size of stable voids
      with increasing temperature, as predicted by the theoretical calculations, shows
      excellent agreement with the experimental findings. The results indicate that
      hollow-structured nanoparticles with an appropriate void-to-total-volume ratio
      can be stable at high temperatures. 

PMID- 26288045
TI  - Dual Transient Bleaching of Au/PbS Hybrid Core/Shell Nanoparticles.
AB  - We examined the optical response of hybrid Au/PbS core/shell nanoparticles (NPs)
      using transient absorption spectroscopy. Finite-difference time-domain (FDTD)
      calculations and transient absorption measurements show that Au/PbS NPs have
      unique two extinction peaks: the peak at the longer wavelength (~700 nm) is
      originated from the plasmon, and that at the shorter wavelength (550 nm) is from
      the local maximum of the refractive index of PbS. The transient absorption
      dynamics of Au/PbS NPs excited at 400 nm have clear oscillation behavior, which
      is assigned to the breathing mode of whole particle. We observed a weak
      excitation-wavelength dependence of the plasmon band. The time constant of
      electron-phonon coupling of Au/PbS NPs was obtained by changing the excitation
      intensity. We show that spectral properties of Au/PbS NPs are strongly altered by
      the hybrid formations, while their dynamics differ only minimally compared with
      those of Au NPs. 

PMID- 26288046
TI  - Nanopatterning of Electrode Surfaces as a Potential Route to Improve the Energy
      Density of Electric Double-Layer Capacitors: Insight from Molecular Simulations.
AB  - Electrostatic double-layer capacitors (EDLCs) with room-temperature ionic liquids
      (RTILs) as electrolytes are among the most promising energy storage technologies.
      Utilizing atomistic molecular dynamics simulations, we demonstrate that the
      capacitance and energy density stored within the electric double layers (EDLs)
      formed at the electrode-RTIL electrolyte interface can be significantly improved
      by tuning the nanopatterning of the electrode surface. Significantly increased
      values and complex dependence of differential capacitance on applied potential
      were observed for surface patterns having dimensions similar to the ions'
      dimensions. Electrode surfaces patterned with rough edges promote ion separation
      in the EDL at lower potentials and therefore result in increased capacitance. The
      observed trends, which are not accounted for by the current basic EDL theories,
      provide a potentially new route for optimizing electrode structure for specific
      electrolytes. 

PMID- 26288047
TI  - New Nano Architecture for SERS Applications.
AB  - Silver silica gold sandwich nanoparticles were synthesized by a multistep seeded
      growth process and were characterized by UV-vis spectroscopy, transmission
      electron microscopy, and X-ray diffraction. Gold islands allow passage of light
      through the crevices into the silica layer, and the silver core-silica shell
      behaves like a mirror, thus reflecting the light incident on it. These structures
      facilitate light amplification due to mixing of light waves from the multiple
      reflections. Sandwich nanoparticles show SERS enhancement of ~10(6). This
      enhancement factor is 6-fold larger in magnitude than that of similar
      nanoparticles without the silver core under identical experimental conditions. 

PMID- 26288048
TI  - Modification of the Mg/DOBDC MOF with Amines to Enhance CO2 Adsorption from
      Ultradilute Gases.
AB  - The MOF Mg/DOBDC has one of the highest known CO2 adsorption capacities at the
      low to moderate CO2 partial pressures relevant for CO2 capture from flue gas but
      is difficult to regenerate for use in cyclic operation. In this work, Mg/DOBDC is
      modified by functionalization of its open metal coordination sites with ethylene
      diamine (ED) to introduce pendent amines into the MOF micropores. DFT
      calculations and experimental nitrogen physisorption and thermogravimetric
      analysis suggest that 1 ED molecule is added to each unit cell, on average. This
      modification both increases the material's CO2 adsorption capacity at ultradilute
      CO2 partial pressures and increases the regenerability of the material, allowing
      for cyclic adsorption-desorption cycles with identical adsorption capacities.
      This is one of the first MOF materials demonstrated to yield significant
      adsorption capacities from simulated ambient air (400 ppm CO2), and its capacity
      is competitive with the best-known adsorbents based on amine-oxide composites. 

PMID- 26288049
TI  - Ground-State Intermolecular Proton Transfer of N2O4 and H2O: An Important Source
      of Atmospheric Hydroxyl Radical?
AB  - To evaluate the significance of the generation of atmospheric hydroxyl radical
      from reaction of N2O4 with H2O, CASPT2//CASSCF as well as CASPT2//CASSCF/Amber
      QM/MM approaches were employed to map the minimum-energy profiles of sequential
      reactions, NO2 dimerization and ground-state intermolecular proton transfer of
      trans-ONONO2 as well as the photolysis of HONO. A highly efficient ground-state
      intermolecular proton transfer of trans-ONONO2 is found to dominate the
      generation of hydroxyl radical under atmospheric conditions. Although proton
      transfer occurs with high efficiency, the precursor reaction of dimerization
      producing trans-ONONO2 has to overcome a 17.1 kcal/mol barrier and cannot compete
      with the barrierless channel of symmetric O2N-NO2 formation from isolated NO2
      monomers. Our computations reveal that the photolysis of HONO without a barrier
      definitely makes significant contributions to the concentration of the
      atmospheric hydroxyl radical, but its importance is influenced by the lack of
      trans-ONONO2 isomer in the atmospheric environment. 

PMID- 26288050
TI  - Electron-Transfer Processes in Zinc Phthalocyanine-Phosphonic Acid Monolayers on
      ITO: Characterization of Orientation and Charge-Transfer Kinetics by Waveguide
      Spectroelectrochemistry.
AB  - Using a monolayer of zinc phthalocyanine (ZnPcPA) tethered to indium tin oxide
      (ITO) as a model for the donor/transparent conducting oxide (TCO) interface in
      organic photovoltaics (OPVs), we demonstrate the relationship between molecular
      orientation and charge-transfer rates using spectroscopic, electrochemical, and
      spectroelectrochemical methods. Both monomeric and aggregated forms of the
      phthalocyanine (Pc) are observed in ZnPcPA monolayers. Potential-modulated
      attenuated total reflectance (PM-ATR) measurements show that the monomeric
      subpopulation undergoes oxidation/reduction with ks,app = 2 * 10(2) s(-1),
      independent of Pc orientation. For the aggregated ZnPcPA, faster orientation
      dependent charge-transfer rates are observed. For in-plane-oriented Pc
      aggregates, ks,app = 2 * 10(3) s(-1), whereas for upright Pc aggregates, ks,app =
      7 * 10(2) s(-1). The rates for the aggregates are comparable to those required
      for redox-active interlayer films at the hole-collection contact in organic solar
      cells. 

PMID- 26288051
TI  - Understanding Gas-Induced Structural Deformation of ZIF-8.
AB  - ZIF-8 is a zeolitic imidazolate framework with very good thermal and chemical
      stability that opens up many applications that are not feasible by other metal
      organic frameowrks (MOFs) and zeolites. Several works report the adsorption
      properties of ZIF-8 for strategic gases. However, despite the vast experimental
      corpus of data reported, there seems yet to be a dearth in the understanding of
      the gas adsorption properties. In this work we provide insights at a molecular
      level on the mechanisms governing the ZIF-8 structural deformation during
      molecular adsorption. We demonstrate that the ZIF-8 structural deformation during
      the adsorption of different molecules at cryogenic temperature goes beyond the
      gas-induced rotation of the imidazolate linkers. We combine experimental and
      simulation studies to demonstrate that this deformation is governed by the
      polarizability and molecular size and shape of the gases, and that the stepped
      adsorption behavior is defined by the packing arrangement of the guest inside the
      host. 

PMID- 26288052
TI  - Comparison of Nuclear Spin Relaxation of H2O@C60 and H2@C60 and Their Nitroxide
      Derivatives.
AB  - The successful synthesis of H2O@C60 makes possible the study of magnetic
      interactions of an isolated water molecule in a geometrically well-defined
      hydrophobic environment. Comparisons are made between the T1 values of H2O@C60
      and the previously studied H2@C60 and their nitroxide derivatives. The value of
      T1 is approximately six times longer for H2O@C60 than for H2@C60 at room
      temperature, is independent of solvent viscosity or polarity, and increases
      monotonically with decreasing temperature, implying that T1 is dominated by the
      spin-rotation interaction. Paramagnetic nitroxides, either attached covalently to
      the C60 cage or added to the medium, produce strikingly similar T1 enhancements
      for H2O@C60 and H2@C60 that are consistent with through-space interaction between
      the internal nuclear spins and the external electron spin. This indicates that it
      should be possible to apply to the endo-H2O molecule the same methodologies for
      manipulating the ortho and para spin isomers that have proven successful for
      H2@C60. 

PMID- 26288053
TI  - Electrical Transport in Colloidal Quantum Dot Films.
AB  - In nanocrystal solids, the small density of states of quantum dots makes it
      difficult to achieve metallic conductivity without band-like transport. However,
      to achieve band-like transport, the energy scale of the disorder should be
      smaller than the coupling energy. This is unlikely with the present systems due
      to the size polydispersivity. Transport by hopping may nevertheless lead to an
      increased mobility with decreasing temperature for some temperature range, and
      such behavior at finite temperature is not proof of band-like conduction. To
      date, at low temperature, variable range hopping in semiconductor or weakly
      coupled metal nanocrystal solids dominates transport, as in disordered
      semiconductors. 

PMID- 26288054
TI  - Gas-Phase Protein Inner-Shell Spectroscopy by Coupling an Ion Trap with a Soft X
      ray Beamline.
AB  - C, N, and O near-edge ion yield spectroscopy of 8+ selected electrosprayed
      cations of cytochrome c protein (12 kDa) has been performed by coupling a linear
      quadrupole ion trap with a soft X-ray beamline. The photoactivation tandem mass
      spectra were recorded as a function of the photon energy. Photoionization of the
      precursor, accompanied by CO2 loss, is the dominant relaxation process, showing
      high photoion stability following direct or resonant photoionization. The partial
      ion yields extracted from recorded mass spectra show significantly different
      behaviors for single and double ionization channels, which can be qualitatively
      explained by different Auger decay mechanisms. However, the single ionization
      spectra reveal characteristic structures when compared to existing near-edge X
      ray absorption fine structure (NEXAFS) spectra from thin films of peptides and
      proteins. Therefore, the present experiment opens up new avenues for near-edge X
      ray spectroscopy of macromolecules in the gas phase, overcoming the radiation
      damage issue or the environmental effects as due to the surface, intermolecular
      interactions, and solvent. 

PMID- 26288055
TI  - Synthesis and Spectroscopic Characterization of Diphenylargentate,
      [(C6H5)2Ag](.).
AB  - We present the structural and optical properties of the isolated
      diphenylargentate anion, which has been synthesized by multistage mass
      spectrometry in a quadrupole ion trap. The experimental photodetachment spectrum
      has been obtained by action spectroscopy. Comparison with quantum chemical
      calculations of the electronic absorption spectrum allows for a precise
      characterization of the spectroscopic features, showing that in the low-energy
      regime, the optical properties of diphenylargentate bear a significant
      resemblance to those of atomic silver. 

PMID- 26288056
TI  - Built-In Potential in Conjugated Polymer Diodes with Changing Anode Work
      Function: Interfacial States and Deviation from the Schottky-Mott Limit.
AB  - We use electroabsorption spectroscopy to measure the change in built-in potential
      (VBI) across the polymer photoactive layer in diodes where indium tin oxide
      electrodes are systematically modified using dipolar phosphonic acid self
      assembled monolayers (SAMs) with various dipole moments. We find that VBI scales
      linearly with the work function (Phi) of the SAM-modified electrode over a wide
      range when using a solution-coated poly(p-phenylenevinylene) derivative as the
      active layer. However, we measure an interfacial parameter of S =
      eDeltaVBI/DeltaPhi < 1, suggesting that these ITO/SAM/polymer interfaces deviate
      from the Schottky-Mott limit, in contrast to what has previously been reported
      for a number of ambient-processed organic-on-electrode systems. Our results
      suggest that the energetics at these ITO/SAM/polymer interfaces behave more like
      metal/organic interfaces previously studied in UHV despite being processed from
      solution. 

PMID- 26288057
TI  - Photoelectrochemical Cell Measurements: Getting the Basics Right.

PMID- 26288058
TI  - Two-Photon Absorption Spectrum of a Single Crystal Cyanine-like Dye.
AB  - The two-photon absorption (2PA) spectrum of an organic single crystal is
      reported. The crystal is grown by self-nucleation of a subsaturated hot solution
      of acetonitrile, and is composed of an asymmetrical donor-pi-acceptor cyanine
      like dye molecule. To our knowledge, this is the first report of the 2PA spectrum
      of single crystals made from a cyanine-like dye. The linear and nonlinear
      properties of the single crystalline material are investigated and compared with
      the molecular properties of a toluene solution of its monomeric form. The maximum
      polarization-dependent 2PA coefficient of the single crystal is 52 +/- 9 cm/GW,
      which is more than twice as large as that for the inorganic semiconductor CdTe
      with a similar absorption edge. The optical properties, linear and nonlinear, are
      strongly dependent upon incident polarization due to anisotropic molecular
      packing. X-ray diffraction analysis shows pi-stacking dimers formation in the
      crystal, similar to H-aggregates. Quantum chemical calculations demonstrate that
      this dimerization leads to the splitting of the energy bands and the appearance
      of new red-shifted 2PA bands when compared to the solution of monomers. This
      trend is opposite to the blue shift in the linear absorption spectra upon H
      aggregation. 

PMID- 26288059
TI  - Clinical characteristics and prognosis of non-B non-C hepatocellular carcinoma
      patients with modest alcohol consumption.
AB  - AIM: Alcoholic hepatocellular carcinoma (ALD-HCC) accounts for the majority of
      non-B non-C HCC (NBNC-HCC) cases. Although alcohol is a potent carcinogen, there
      have been few reports on the influence of modest alcohol consumption in NBNC-HCC.
      This study aimed to investigate the clinical characteristics and prognosis of
      NBNC-HCC patients with modest alcohol consumption. METHODS: From 2007 to 2010,
      2283 HCC patients were evaluated at 10 hospitals. We collected detailed etiology
      data of 588 NBNC-HCC patients and compared the clinical characteristics and
      prognosis between ALD-HCC and modest alcohol-HCC patients. RESULTS: There were 69
      HCC patients with modest alcohol consumption, accounting for 3% of all HCC
      patients evaluated. This patient group had significantly more women and higher
      prevalence of Child-Pugh class A, hypertension and advanced disease stage, and
      were diagnosed with HCC at an older age than the ALD-HCC group (266 patients).
      Additionally, among the modest alcohol-HCC patients, diabetes was significantly
      more common in the anti-hepatitis B core (HBc) negative subgroup than in the anti
      HBc positive subgroup. However, no significant difference in survival was
      observed between the two patient groups regardless of significant differences in
      tumor staging. Alcohol consumption and metabolic factors were not significant
      independent predictors of survival. CONCLUSION: The clinical characteristics of
      modest alcohol-HCC included advanced staging, favorable liver reserve capacity
      and older age at diagnosis. HCC development in patients with modest alcohol
      consumption may relate to metabolic factors. Although approximately 30% of the
      evaluated HCC cases were in advanced stages, the prognosis of NBNC-HCC patients
      with modest alcohol consumption was relatively favorable.

PMID- 26288060
TI  - PET Imaging of Dll4 Expression in Glioblastoma and Colorectal Cancer Xenografts
      Using (64)Cu-Labeled Monoclonal Antibody 61B.
AB  - Delta-like ligand 4 (Dll4) expressed in tumor cells plays a key role to promote
      tumor growth of numerous cancer types. Based on a novel antihuman Dll4 monoclonal
      antibody (61B), we developed a (64)Cu-labeled probe for positron emission
      tomography (PET) imaging of tumor Dll4 expression. In this study, 61B was
      conjugated with the (64)Cu-chelator DOTA through lysine on the antibody. Human
      IgG (hIgG)-DOTA, which did not bind to Dll4, was also prepared as a control. The
      Dll4 binding activity of the probes was evaluated through the bead-based binding
      assay with Dll4-alkaline phosphatase. The resulting PET probes were evaluated in
      U87MG glioblastoma and HT29 colorectal cancer xenografts in athymic nude mice.
      Our results demonstrated that the 61B-DOTA retained (77.2 +/- 3.7) % Dll4 binding
      activity of the unmodified 61B, which is significantly higher than that of hIgG
      DOTA (0.06 +/- 0.03) %. Confocal microscopy analysis confirmed that 61B-Cy5.5,
      but not IgG-Cy5.5, predominantly located within the U87MG and HT29 cells
      cytoplasm. U87MG cells showed higher 61B-Cy5.5 binding as compared to HT29 cells.
      In U87MG xenografts, 61B-DOTA-(64)Cu demonstrated remarkable tumor accumulation
      (10.5 +/- 1.7 and 10.2 +/- 1.2%ID/g at 24 and 48 h postinjection, respectively).
      In HT29 xenografts, tumor accumulation of 61B-DOTA-(64)Cu was significantly lower
      than that of U87MG (7.3 +/- 1.3 and 6.6 +/- 1.3%ID/g at 24 and 48 h
      postinjection, respectively). The tumor accumulation of 61B-DOTA-(64)Cu was
      significantly higher than that of hIgG-DOTA-(64)Cu in both xenografts models.
      Immunofluorescence staining of the tumor tissues further confirmed that tumor
      accumulation of 61B-Cy5.5 was correlated well with in vivo PET imaging data using
      61B-DOTA-(64)Cu. In conclusion, 61B-DOTA-(64)Cu PET probe was successfully
      synthesized and demonstrated prominent tumor uptake by targeting Dll4. 61B-DOTA
      (64)Cu has great potential to be used for noninvasive Dll4 imaging, which could
      be valuable for tumor detection, Dll4 expression level evaluation, and Dll4-based
      treatment monitoring. 

PMID- 26288062
TI  - Relationship between pelvic floor muscle and hormone levels in polycystic ovary
      syndrome.
AB  - AIMS: To evaluate the electrical activity of the pelvic floor muscles (PFM) in
      women with polycystic ovary syndrome. METHODS: Forty-two women with polycystic
      ovary syndrome (PCOS group) and 13 premenopausal women (control group) were
      recruited in this cross-sectional study. Total testosterone and estradiol were
      measured and muscle tone and maximum voluntary contraction (MVC) of PFM were
      determined by surface electromyography. RESULTS: There was a difference in muscle
      tone (PCOS = 59.9 uV and Control group = 25.5 uV; P < 0.0001) and MVC (PCOS =
      159.7 uV and Control group = 63.7 uV; P < 0.0002) between groups. The
      concentration of estradiol and testosterone showed a strong correlation with tone
      (r = 0.9, r = 0.8 respectively) and MVC (r = 0.9, r = 0.9 respectively) in women
      with PCOS. The control group exhibited a strong correlation between testosterone
      and muscle tone (r = 0.9) and MVC (r = 0.9). CONCLUSION: Women with PCOS display
      higher electromyographic values than those in premenopause. Moreover, electrical
      activity showed a positive relation with estradiol and testosterone
      concentrations. Although PCOS is a heterogeneous disorder affecting young women,
      it is suggested that the hyperandrogenic state associated with PCOS is a
      protective factor for PFM. Neurourol. Urodynam. 35:780-785, 2016. (c) 2015 Wiley
      Periodicals, Inc.

PMID- 26288063
TI  - Conducting systematic reviews of economic evaluations.
AB  - BACKGROUND: In 2012, a working group was established to review and enhance the
      Joanna Briggs Institute (JBI) guidance for conducting systematic review of
      evidence from economic evaluations addressing a question(s) about health
      intervention cost-effectiveness. OBJECTIVES: The objective is to present the
      outcomes of the working group. METHODS: The group conducted three activities to
      inform the new guidance: review of literature on the utility/futility of
      systematic reviews of economic evaluations and consideration of its implications
      for updating the existing methodology; assessment of the critical appraisal tool
      in the existing guidance against criteria that promotes validity in economic
      evaluation research and two other commonly used tools; and a workshop. RESULTS:
      The debate in the literature on the limitations/value of systematic review of
      economic evidence cautions that systematic reviews of economic evaluation
      evidence are unlikely to generate one size fits all answers to questions about
      the cost-effectiveness of interventions and their comparators. Informed by this
      finding, the working group adjusted the framing of the objectives definition in
      the existing JBI methodology. The shift is away from defining the objective as to
      determine one cost-effectiveness measure toward summarizing study estimates of
      cost-effectiveness and informed by consideration of the included study
      characteristics (patient, setting, intervention component, etc.), identifying
      conditions conducive to lowering costs and maximizing health benefits. The
      existing critical appraisal tool was included in the new guidance. The new
      guidance includes the recommendation that a tool designed specifically for the
      purpose of appraising model-based studies be used together with the generic
      appraisal tool for economic evaluations assessment to evaluate model-based
      evaluations. The guidance produced by the group offers reviewers guidance for
      each step of the systematic review process, which are the same steps followed in
      JBI reviews of other types of evidence. DISCUSSION: The updated JBI guidance will
      be useful for researchers wanting to synthesize evidence about economic
      questions, either as stand-alone reviews or part of comprehensive or mixed method
      evidence reviews. Although the updated methodology produced by the work of the
      working group has improved the JBI guidance for systematic reviews of economic
      evaluations, there are areas where further work is required. These include
      adjusting the critical appraisal tool to separate out questions addressing
      intervention cost and effectiveness measurement; providing more explicit guidance
      for assessing generalizability of findings; and offering a more robust method for
      evidence synthesis that facilitates achieving the more ambitious review
      objectives.

PMID- 26288064
TI  - Supramolecular Chemistry in Microflow Fields: Toward a New Material World of
      Precise Kinetic Control.
AB  - Constructing new and versatile self-assembling systems in supramolecular
      chemistry is much like the development of new reactions or new catalysts in
      synthetic organic chemistry. As one such new technology, conventional
      supramolecular assembly systems have been combined with microflow techniques to
      control intermolecular or interpolymer interactions through precise regulation of
      a flowing self-assembly field. The potential of the microflow system has been
      explored by using various simple model compounds. Uniform solvent diffusion in
      the microflow leads to rapid activation of molecules in a nonequilibrium state
      and, thereby, enhanced interactions. All of these self-assembly processes begin
      from a temporally activated state and proceed in a uniform chemical environment,
      forming a synchronized cluster and resulting in effective conversion to
      supramolecules, with precise tuning of molecular (or polymer) interactions. This
      approach allows the synthesis of a variety of discrete microstructures (e.g.,
      fibers, sheets) and unique supramolecules (e.g., hierarchical assemblies, capped
      fibers, polymer networks, supramolecules with time-delayed action) that have
      previously been inaccessible. 

PMID- 26288065
TI  - A New Cubic Phase for a NaYF4 Host Matrix Offering High Upconversion Luminescence
      Efficiency.
AB  - A NaYF4 host matrix with a new cubic phase is fabricated to offer high
      upconversion luminescence efficiency. The new cubic phase is formed through a
      hexagonal-to-cubic phase transition by shining intense near-infrared light on
      lanthanide-doped hexagonal NaYF4 materials. 

PMID- 26288067
TI  - Effect of LED Blue Light on Penicillium digitatum and Penicillium italicum
      Strains.
AB  - Studies on the antimicrobial properties of light have considerably increased due
      in part to the development of resistance to actual control methods. This study
      investigates the potential of light-emitting diodes (LED) blue light for
      controlling Penicillium digitatum and Penicillium italicum. These fungi are the
      most devastating postharvest pathogens of citrus fruit and cause important losses
      due to contaminations and the development of resistant strains against
      fungicides. The effect of different periods and quantum fluxes, delaying light
      application on the growth and morphology of P. digitatum strains resistant and
      sensitive to fungicides, and P. italicum cultured at 20 degrees C was examined.
      Results showed that blue light controls the growth of all strains and that its
      efficacy increases with the quantum flux. Spore germination was always avoided by
      exposing the cultures to high quantum flux (700 MUmol m(-2) s(-1) ) for 18 h.
      Continuous light had an important impact on the fungus morphology and a
      fungicidal effect when applied at a lower quantum flux (120 MUmol m(-2) s(-1) )
      to a growing fungus. Sensitivity to light increased with mycelium age. Results
      show that blue light may be a tool for P. digitatum and P. italicum infection
      prevention during handling of citrus fruits. 

PMID- 26288068
TI  - Association Between Total Hip Replacement Characteristics and 3-Year Prosthetic
      Survivorship: A Population-Based Study.
AB  - IMPORTANCE: Total hip replacement (THR) is successful in treating hip arthritis.
      Prosthetic survivorship may depend on characteristics of the implant, notably THR
      fixation technique and bearing surface type. OBJECTIVE: To compare THR short-term
      survivorship according to cement type and bearing surface. DESIGN, SETTING, AND
      PARTICIPANTS: The cohort included all French patients aged 40 years or older
      covered by the general scheme of the French national health insurance system who
      had undergone THR from April 1, 2010, through December 31, 2011, for arthritis,
      according to French national health insurance databases. The cohort was followed
      up until December 31, 2013. The THR survivorship was assessed according to cement
      type and bearing surface in univariate and multivariate Cox proportional hazards
      regression models adjusted for patient and implanting center characteristics.
      EXPOSURES: Antibiotic-free cemented THRs and antibiotic-impregnated cemented THRs
      were compared with uncemented THRs. Ceramic-on-ceramic (CoC), ceramic-on
      polyethylene (CoP), and metal-on-metal (MoM) THRs were compared with metal-on
      polyethylene (MoP) THRs. MAIN OUTCOMES AND MEASURES: Revision, including any
      surgical reintervention in which the implant or any of its components was changed
      or removed. RESULTS: The study cohort comprised 100 191 individuals: mean age at
      baseline, 69.5 years; women, 56.6%; uncemented THR, 74.8%; antibiotic-free
      cemented THR, 3.8%; antibiotic-impregnated cemented THR, 21.4%; CoC, 40.9%; MoP,
      33.9%; CoP, 20.8%; and MoM, 4.4%. During the median 33-month follow-up period,
      3142 individuals underwent prosthetic revision. Antibiotic-impregnated cemented
      THRs had a better prognosis than uncemented THRs: cumulative revision rates were
      2.4% and 3.3%, respectively (P < .001), and the multivariate adjusted hazard
      ratio was 0.75 (95% CI, 0.67-0.84; P < .001). This association was particularly
      significant in women. The CoP and CoC THRs were no different from the MoP THR.
      The MoM THR had slightly shorter survivorship compared with the MoP THR (adjusted
      hazard ratio, 1.20; 95% CI, 1.01-1.43; P < .001). CONCLUSIONS AND RELEVANCE:
      Characteristics of THR are related to early prosthetic revision: antibiotic
      impregnated cemented THRs have a better prognosis and MoM THRs a worse one. These
      findings are useful in helping surgeons select a THR fixation technique and
      helpful for both patient and surgeon in the decision-making process.

PMID- 26288066
TI  - Mitochondrial Analysis of the Most Basal Canid Reveals Deep Divergence between
      Eastern and Western North American Gray Foxes (Urocyon spp.) and Ancient Roots in
      Pleistocene California.
AB  - Pleistocene aridification in central North America caused many temperate forest
      associated vertebrates to split into eastern and western lineages. Such divisions
      can be cryptic when Holocene expansions have closed the gaps between once
      disjunct ranges or when local morphological variation obscures deeper regional
      divergences. We investigated such cryptic divergence in the gray fox (Urocyon
      cinereoargenteus), the most basal extant canid in the world. We also investigated
      the phylogeography of this species and its diminutive relative, the island fox
      (U. littoralis), in California. The California Floristic Province was a
      significant source of Pleistocene diversification for a wide range of taxa and,
      we hypothesized, for the gray fox as well. Alternatively, gray foxes in
      California potentially reflected a recent Holocene expansion from further south.
      We sequenced mitochondrial DNA from 169 gray foxes from the southeastern and
      southwestern United States and 11 island foxes from three of the Channel Islands.
      We estimated a 1.3% sequence divergence in the cytochrome b gene between eastern
      and western foxes and used coalescent simulations to date the divergence to
      approximately 500,000 years before present (YBP), which is comparable to that
      between recognized sister species within the Canidae. Gray fox samples collected
      from throughout California exhibited high haplotype diversity, phylogeographic
      structure, and genetic signatures of a late-Holocene population decline. Bayesian
      skyline analysis also indicated an earlier population increase dating to the
      early Wisconsin glaciation (~70,000 YBP) and a root height extending back to the
      previous interglacial (~100,000 YBP). Together these findings support
      California's role as a long-term Pleistocene refugium for western Urocyon.
      Lastly, based both on our results and re-interpretation of those of another
      study, we conclude that island foxes of the Channel Islands trace their origins
      to at least 3 distinct female founders from the mainland rather than to a single
      matriline, as previously suggested. 

PMID- 26288069
TI  - Outcomes of pregnancies with more than one positive prenatal screening result in
      the first or second trimester.
AB  - OBJECTIVE: To describe adverse outcomes and fetal abnormalities in women with a
      positive prenatal screening result for more than one disorder. STUDY DESIGN:
      Study participants were drawn from a population of 452 901 women pregnant with
      singletons entering the California Prenatal Screening Program in their first
      trimester. Risk assessment was provided for trisomy 21 and trisomy 18 in the
      first-trimester and trisomy 21, trisomy 18, neural tube defects, and Smith-Lemli
      Opitz syndrome in the second-trimester. Inclusion in this study required positive
      screening for more than one of the screened conditions and a completed outcome of
      pregnancy survey. RESULTS: A total of 874 women met our study inclusion criteria.
      Over 25% of these pregnancies had a fetus with a chromosomal abnormality. Of the
      euploid pregnancies, 6.9% had a fetus with a major birth defect. Of the
      pregnancies with a fetus with neither a chromosomal abnormality nor a major birth
      defect, 9.3% ended in fetal demise. Overall, more than 50% of women with multiple
      positive screening results had either a fetus with a birth defect or a poor
      pregnancy outcome. CONCLUSION: Although it is rare to screen positive for more
      than one condition, such results indicate a very high risk for chromosomal
      abnormality, fetal demise, or structural abnormality.

PMID- 26288074
TI  - Genetic factors may underlie many cerebral palsy cases: New research implicates
      genetic variations, not lack of oxygen at birth, in disorder.

PMID- 26288070
TI  - Influence of Dietary Experience on the Induction of Preference of Adult Moths and
      Larvae for a New Olfactory Cue.
AB  - In Lepidoptera, host plant selection is first conditioned by oviposition site
      preference of adult females followed by feeding site preference of larvae.
      Dietary experience to plant volatile cues can induce larval and adult host plant
      preference. We investigated how the parent's and self-experience induce host
      preference in adult females and larvae of three lepidopteran stem borer species
      with different host plant ranges, namely the polyphagous Sesamia nonagrioides,
      the oligophagous Busseola fusca and the monophagous Busseola nairobica, and
      whether this induction can be linked to a neurophysiological phenotypic
      plasticity. The three species were conditioned to artificial diet enriched with
      vanillin from the neonate larvae to the adult stage during two generations.
      Thereafter, two-choice tests on both larvae and adults using a Y-tube
      olfactometer and electrophysiological (electroantennography [EAG] recordings)
      experiments on adults were carried out. In the polyphagous species, the induction
      of preference for a new olfactory cue (vanillin) by females and 3rd instar larvae
      was determined by parents' and self-experiences, without any modification of the
      sensitivity of the females antennae. No preference induction was found in the
      oligophagous and monophagous species. Our results suggest that lepidopteran stem
      borers may acquire preferences for new olfactory cues from the larval to the
      adult stage as described by Hopkins' host selection principle (HHSP), neo
      Hopkins' principle, and the concept of 'chemical legacy.' 

PMID- 26288075
TI  - Copy number variants linked to intellectual disability, less education: Study
      shows even moderate genetic duplications, deletions can affect cognitive ability.

PMID- 26288071
TI  - The Prion Protein Controls Polysialylation of Neural Cell Adhesion Molecule 1
      during Cellular Morphogenesis.
AB  - Despite its multi-faceted role in neurodegenerative diseases, the physiological
      function of the prion protein (PrP) has remained elusive. On the basis of its
      evolutionary relationship to ZIP metal ion transporters, we considered that PrP
      may contribute to the morphogenetic reprogramming of cells underlying epithelial
      to-mesenchymal transitions (EMT). Consistent with this hypothesis, PrP
      transcription increased more than tenfold during EMT, and stable PrP-deficient
      cells failed to complete EMT in a mammalian cell model. A global comparative
      proteomics analysis identified the neural cell adhesion molecule 1 (NCAM1) as a
      candidate mediator of this impairment, which led to the observation that PrP
      deficient cells fail to undergo NCAM1 polysialylation during EMT. Surprisingly,
      this defect was caused by a perturbed transcription of the polysialyltransferase
      ST8SIA2 gene. Proteomics data pointed toward beta-catenin as a transcriptional
      regulator affected in PrP-deficient cells. Indeed, pharmacological blockade or
      siRNA-based knockdown of beta-catenin mimicked PrP-deficiency in regards to NCAM1
      polysialylation. Our data established the existence of a PrP-ST8SIA2-NCAM
      signaling loop, merged two mature fields of investigation and offer a simple
      model for explaining phenotypes linked to PrP. 

PMID- 26288077
TI  - Expanding the Versatility of Dipicolinate-Based Luminescent Lanthanide Complexes:
      A Fast Method for Antenna Testing.
AB  - A dipicolinate (dpa)-based platform for the rapid testing of potential lanthanide
      sensitizing antennae was developed; 4-methyl-7-O-alkylcoumarin-appended dpa could
      sensitize four lanthanides. The platform could be used to estimate the
      photophysical properties of a more difficult-to-prepare 1,4,7,10
      tetraazacyclododecane-1,4,7-triacetic acid based structure carrying the same
      antenna. 

PMID- 26288078
TI  - A microscale turbine driven by diffusive mass flux.
AB  - An external diffusive mass flux is shown to be able to generate a mechanical
      torque on a microscale object based on anisotropic diffusiophoresis. In light of
      this finding, we propose a theoretical prototype micro-turbine driven purely by
      diffusive mass flux, which is in strong contrast to conventional turbines driven
      by convective mass flows. The rotational velocity of the proposed turbine is
      determined by the external concentration gradient, the geometry and the
      diffusiophoretic properties of the turbine. This scenario is validated by
      performing computer simulations. Our finding thus provides a new type of chemo
      mechanical response which could be used to exploit existing chemical energies at
      small scales. 

PMID- 26288079
TI  - A Century of Tuberculosis Epidemiology in the Northern and Southern Hemisphere:
      The Differential Impact of Control Interventions.
AB  - BACKGROUND: Cape Town has one of the highest TB burdens of any city in the world.
      In 1900 the City of Cape Town, New York City and London had high mortality of
      tuberculosis (TB). Throughout the 20th century contemporaneous public health
      measures including screening, diagnosis and treatment were implemented in all
      three settings. Mandatory notification of TB and vital status enabled comparison
      of disease burden trajectories. METHODS: TB mortality, notification and case
      fatality rates were calculated from 1912 to 2012 using annual TB notifications,
      TB death certifications and population estimates. Notification rates were
      stratified by age and in Cape Town by HIV status (from 2009 onwards). RESULTS:
      Pre-chemotherapy, TB mortality and notification rates declined steadily in New
      York and London but remained high in Cape Town. Following introduction of
      combination chemotherapy, mean annual case fatality dropped from 45-60% to below
      10% in all three settings. Mortality and notification rates subsequently
      declined, although Cape Town notifications did not decline as far as those in New
      York or London and returned to pre-chemotherapy levels by 1980. The proportional
      contribution of childhood TB diminished in New York and London but remained high
      in Cape Town. The advent of the Cape Town HIV-epidemic in the 1990s was
      associated with a further two-fold increase in incidence. In 2012, notification
      rates among HIV-negatives remained at pre-chemotherapy levels. CONCLUSIONS: TB
      control was achieved in New York and London but failed in Cape Town. The TB
      disease burden trajectories started diverging before the availability of
      combination chemotherapy in 1952 and further diverged following the HIV epidemic
      in 1990. Chemotherapy impacted case fatality but not transmission, evidenced by
      on-going high childhood TB rates. Currently endemic TB results from high on-going
      transmission, which has been exacerbated by the HIV epidemic. TB control will
      require reducing transmission, which is inexorably linked to prevailing socio
      economic factors.

PMID- 26288080
TI  - The Chemical Diversity of the Ascomycete Fungus Paecilomyces variotii.
AB  - Paecilomyces variotii isolated from a broad range of habitats drives the
      diversification of new high-value-added secondary metabolites that could
      potentially play an important role in human and animal health. These metabolites
      include the anhydride metabolite of the nonadride family, as well as the
      following compounds: naphthopyranone metabolites, sphingofungins, eicosenoic
      acids, new branched fatty acids, ascofuranone, polyketides, an anacardic acid
      analogue, straight-chain peptides, and volatile compounds. These natural products
      show that P. variotii can provide leading compounds for new drug discoveries,
      which may include herbicide agents, some of which are important in the
      agrochemical market. Finally, this review outlines recent developments, trends,
      and prospects for the chemistry of this ascomycete.

PMID- 26288081
TI  - An Injectable PEG-BSA-Coumarin-GOx Hydrogel for Fluorescence Turn-on Glucose
      Detection.
AB  - Diabetes mellitus is a chronic metabolic disorder, requiring vigilant monitoring
      of blood glucose levels. In this study, an injectable fluorescent enzymatic
      hydrogel was designed for rapid glucose detection. The leakage-free glucose
      responsive hydrogel was constructed by the covalent linkage of a multi-arm poly
      (ethylene glycol) (PEG), bovine serum albumin (BSA), glucose oxidase (GOx), and 4
      (aminomethyl)-6,7-dimethoxycoumarin (Coumarin-NH2). The GOx serves as glucose
      recognition element and the pH-sensitive Coumarin-NH2 as a fluorescence turn-on
      reporter. The material properties of the fluorescent hydrogel were systematically
      characterized which show high elasticity with good mechanical strength. Upon the
      addition of glucose, the as-developed fluorescent hydrogel shows a fast response
      time, good sensitivity, and good reproducibility at physiological pH and ambient
      temperature. The glucose-sensing mechanism is based on the oxidation of the
      glucose by GOx that generates protons to change the local pH. Consequently,
      protonation of the covalently immobilized and pH-sensitive Coumarin-NH2 turns on
      the fluorescence of the coumarin. The fluorescence hydrogel developed holds great
      promise as an injectable, implantable glucose-sensing biomaterials for in vivo
      continuous glucose monitoring. 

PMID- 26288082
TI  - Postsynthetic Domain Assembly with NpuDnaE and SspDnaB Split Inteins.
AB  - Inteins are protein segments embedded in frame within a precursor sequence that
      catalyze a self-excision reaction and ligate the flanking sequences with a
      standard peptide bond. Split inteins are expressed as two separate polypeptide
      fragments and trans-splice upon subunit association. Split inteins have found use
      in biotechnology applications but their use in postsynthetic domain assembly in
      vivo has been limited to the ligation of two protein domains. Alternatively, they
      have been used to splice three domains and fragments in vitro. To further develop
      split intein-based applications in vivo, we have designed a cell-based assay for
      the postsynthetic splicing of three protein domains using orthogonal split
      inteins. Using naturally and artificially split inteins, NpuDnaE and SspDnaB, we
      show that a multidomain protein of 128 kDa can be assembled in Escherichia coli
      from individually expressed domains. In the current system, the main bottleneck
      in achieving high yield of tandem trans-spliced product appears to be the limited
      solubility of the SspDnaB precursors. Optimizing protein solubility should be
      important to achieve efficient combinatorial synthesis of protein domains in the
      cell. 

PMID- 26288083
TI  - Characterization of Novel Cellulase-producing Bacteria Isolated From Rotting Wood
      Samples.
AB  - Seventeen bacterial isolates were screened for their cellulase activity by
      carboxymethyl cellulose (CMC) plate assay. The bacterial strain K1 showed the
      largest depolymerized region in CMC plate assay and was further studied for
      quantitative cellulase activity. On the basis of 16S rDNA sequence analysis, the
      strain K1 was found to be Bacillus sp. This strain produced the maximum CMCase at
      pH 6 and 50  degrees C in the presence of peptone (1%) as a source of nitrogen.
      The CMCase activity was stimulated by Ca(2+) (2 mM) by 20% over the control. The
      CMCase activity of this Bacillus sp. K1 was highly induced when lactose was used
      as a source of carbon during fermentation.

PMID- 26288084
TI  - Navigating the human hippocampus without a GPS.

PMID- 26288085
TI  - The role of postnatal neurogenesis in supporting remote memory and spatial metric
      processing.

PMID- 26288086
TI  - Binding Isotope Effects for para-Aminobenzoic Acid with Dihydropteroate Synthase
      from Staphylococcus aureus and Plasmodium falciparum.
AB  - Dihydropteroate synthase is a key enzyme in folate biosynthesis and is the target
      of the sulfonamide class of antimicrobials. Equilibrium binding isotope effects
      and density functional theory calculations indicate that the substrate binding
      sites for para-aminobenzoic acid on the dihydropteroate synthase enzymes from
      Staphylococcus aureus and Plasmodium falciparum present distinct chemical
      environments. Specifically, we show that para-aminobenzoic acid occupies a more
      sterically constrained vibrational environment when bound to dihydropteroate
      synthase from P. falciparum relative to that of S. aureus. Deletion of a
      nonhomologous, parasite-specific insert from the plasmodial dihydropteroate
      synthase abrogated the binding of para-aminobenzoic acid. The loop specific to P.
      falciparum is important for effective substrate binding and therefore plays a
      role in modulating the chemical environment at the substrate binding site. 

PMID- 26288087
TI  - Osteonecrosis of the Jaw in the United States Food and Drug Administration's
      Adverse Event Reporting System (FAERS).
AB  - Osteonecrosis of the jaw (ONJ) is a serious adverse drug event that was initially
      reported with intravenous bisphosphonates (BPs) and more recently with other
      classes of drugs such as receptor activator of NF-kappaB ligand (RANKL)
      inhibitor, antiangiogenic agents, and mammalian target of rapamycin (m-TOR)
      inhibitors. The purpose of this study is to analyze the ONJ cases and the
      associated drugs in the US Food and Drug Administration's adverse event reporting
      system (FAERS). The FAERS database was queried for the adverse drug events
      reported from the first quarter of 2010 to the first quarter of 2014. The
      reporting odds ratios (ORs) and 95% confidence intervals (CIs) were calculated
      for each queried drug. A total of 17,119 unique ONJ cases were identified. In the
      overall analysis, the drugs with the highest reporting ORs were BPs: pamidronate
      (OR = 498.9), zoledronate (OR = 171.7), and alendronate (OR = 63.6), whereas
      denosumab had lower ORs than all the BPs except for etidronate. The
      antiangiogenic and m-TOR inhibitors had the lowest ORs. In cancer patients who
      were treated for prevention of skeletal-related events (SREs), the reporting ORs
      for zoledronate and denosumab were 125.2 and 4.9, respectively. In patients with
      osteoporosis, the ORs were 1.1 (1.0-1.18) for zoledronate and 0.63 (0.56-0.70)
      for denosumab, respectively. Our analysis of the FAERS database showed that the
      intravenous BPs were associated with the highest risk for ONJ, RANKL inhibitor
      was associated with risk comparable to BPs used for osteoporosis such as
      etidronate, and the antiangiogenic agents and m-TOR inhibitors were associated
      with the lowest risk for ONJ. The high risk for ONJ with zoledronate and
      denosumab was mainly observed in those who were treated for prevention of SREs,
      whereas there was limited evidence for such risk in those who were treated for
      osteoporosis.

PMID- 26288088
TI  - On Nash Equilibrium and Evolutionarily Stable States That Are Not Characterised
      by the Folk Theorem.
AB  - In evolutionary game theory, evolutionarily stable states are characterised by
      the folk theorem because exact solutions to the replicator equation are difficult
      to obtain. It is generally assumed that the folk theorem, which is the
      fundamental theory for non-cooperative games, defines all Nash equilibria in
      infinitely repeated games. Here, we prove that Nash equilibria that are not
      characterised by the folk theorem do exist. By adopting specific reactive
      strategies, a group of players can be better off by coordinating their actions in
      repeated games. We call it a type-k equilibrium when a group of k players
      coordinate their actions and they have no incentive to deviate from their
      strategies simultaneously. The existence and stability of the type-k equilibrium
      in general games is discussed. This study shows that the sets of Nash equilibria
      and evolutionarily stable states have greater cardinality than classic game
      theory has predicted in many repeated games. 

PMID- 26288090
TI  - Disability through a Native American lens: examining influences of culture and
      colonization.
AB  - Disability is a socially constructed identity. What constitutes a disability and
      what it means to be a person with a disability can vary across cultures. This
      article explores meanings of disability within Native American cultures,
      including how ideas about wellness, balance, roles, and responsibilities
      influence perceptions of disabilities. This is followed by a review of disability
      prevalence, discussion of services, and explorations of possible reasons for the
      disproportionate impact of disabilities in Native American populations. The
      article concludes with an examination of how the colonial context frames both
      attitudes about and services for Native Americans with disabilities. 

PMID- 26288089
TI  - Benefits and Challenges of Scaling Up Expansion of Marine Protected Area Networks
      in the Verde Island Passage, Central Philippines.
AB  - Locally-established marine protected areas (MPAs) have been proven to achieve
      local-scale fisheries and conservation objectives. However, since many of these
      MPAs were not designed to form ecologically-connected networks, their
      contributions to broader-scale goals such as complementarity and connectivity can
      be limited. In contrast, integrated networks of MPAs designed with systematic
      conservation planning are assumed to be more effective--ecologically, socially,
      and economically--than collections of locally-established MPAs. There is,
      however, little empirical evidence that clearly demonstrates the supposed
      advantages of systematic MPA networks. A key reason is the poor record of
      implementation of systematic plans attributable to lack of local buy-in. An
      intermediate scenario for the expansion of MPAs is scaling up of local decisions,
      whereby locally-driven MPA initiatives are coordinated through collaborative
      partnerships among local governments and their communities. Coordination has the
      potential to extend the benefits of individual MPAs and perhaps to approach the
      potential benefits offered by systematic MPA networks. We evaluated the benefits
      of scaling up local MPAs to form networks by simulating seven expansion scenarios
      for MPAs in the Verde Island Passage, central Philippines. The scenarios were:
      uncoordinated community-based establishment of MPAs; two scenarios reflecting
      different levels of coordinated MPA expansion through collaborative partnerships;
      and four scenarios guided by systematic conservation planning with different
      contexts for governance. For each scenario, we measured benefits through time in
      terms of achievement of objectives for representation of marine habitats. We
      found that: in any governance context, systematic networks were more efficient
      than non-systematic ones; systematic networks were more efficient in broader
      governance contexts; and, contrary to expectations but with caveats, the
      uncoordinated scenario was slightly more efficient than the coordinated
      scenarios. Overall, however, coordinated MPA networks have the potential to be
      more efficient than the uncoordinated ones, especially when coordinated planning
      uses systematic methods.

PMID- 26288092
TI  - The Retina of Ansorge's Cusimanse (Crossarchus ansorgei): Number, Topography and
      Convergence of Photoreceptors and Ganglion Cells in Relation to Ecology and
      Behavior.
AB  - The family Herpestidae (cusimanses and mongooses) is a monophyletic radiation of
      carnivores with remarkable variation in microhabitat occupation and diel
      activity, but virtually nothing is known about how they use vision in the context
      of their behavioral ecology. In this paper, we measured the number and
      topographic distribution of neurons (rods, cones and retinal ganglion cells) and
      estimated the spatial resolving power of the eye of the diurnal, forest-dwelling
      Ansorge's cusimanse (Crossarchus ansorgei). Using retinal wholemounts and
      stereology, we found that rods are more numerous (42,500,000; 92%) than cones
      (3,900,000; 8%). Rod densities form a concentric and dorsotemporally asymmetric
      plateau that matches the location and shape of a bright yellow tapetum lucidum
      located within the dorsal aspect of the eye. Maximum rod density (340,300
      cells/mm(2)) occurs within an elongated plateau below the optic disc that
      corresponds to a transitional region between the tapetum lucidum and the
      pigmented choroid. Cone densities form a temporal area with a peak density of
      44,500 cells/mm(2) embedded in a weak horizontal streak that matches the
      topographic distribution of retinal ganglion cells. Convergence ratios of cones
      to retinal ganglion cells vary from 50:1 in the far periphery to 3:1 in the
      temporal area. With a ganglion cell peak density of 13,400 cells/mm(2) and an eye
      size of 11 mm in axial length, we estimated upper limits of spatial resolution of
      7.5-8 cycles/degree, which is comparable to other carnivores such as hyenas. In
      conclusion, we suggest that the topographic retinal traits described for
      Ansorge's cusimanse conform to a presumed carnivore retinal blueprint but also
      show variations that reflect its specific ecological needs.

PMID- 26288091
TI  - The Effect of Online Hemodiafiltration on Infections: Results from the CONvective
      TRAnsport STudy.
AB  - BACKGROUND: Hemodialysis (HD) patients have a high risk of infections. The uremic
      milieu has a negative impact on several immune responses. Online
      hemodiafiltration (HDF) may reduce the risk of infections by ameliorating the
      uremic milieu through enhanced clearance of middle molecules. Since there are few
      data on infectious outcomes in HDF, we compared the effects of HDF with low-flux
      HD on the incidence and type of infections. PATIENTS AND METHODS: We used data of
      the 714 HD patients (age 64 +/-14, 62% men, 25% Diabetes Mellitus, 7% catheters)
      participating in the CONvective TRAnsport STudy (CONTRAST), a randomized
      controlled trial evaluating the effect of HDF as compared to low-flux HD. The
      events were adjudicated by an independent event committee. The risk of infectious
      events was compared with Cox regression for repeated events and Cox proportional
      hazard models. The distributions of types of infection were compared between the
      groups. RESULTS: Thirty one percent of the patients suffered from one or more
      infections leading to hospitalization during the study (median follow-up 1.96
      years). The risk for infections during the entire follow-up did not differ
      significantly between treatment arms (HDF 198 and HD 169 infections in 800 and
      798 person-years respectively, hazard ratio HDF vs. HD 1.09 (0.88-1.34), P =
      0.42. No difference was found in the occurrence of the first infectious event
      (either fatal, non-fatal or type specific). Of all infections, respiratory
      infections (25% in HDF, 28% in HD) were most common, followed by
      skin/musculoskeletal infections (21% in HDF, 13% in HD). CONCLUSIONS: HDF as
      compared to HD did not result in a reduced risk of infections, larger studies are
      needed to confirm our findings. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00205556.

PMID- 26288093
TI  - Emergence of Lamivudine-Resistant HBV during Antiretroviral Therapy Including
      Lamivudine for Patients Coinfected with HIV and HBV in China.
AB  - In China, HIV-1-infected patients typically receive antiretroviral therapy (ART)
      that includes lamivudine (3TC) as a reverse-transcriptase inhibitor (RTI) (ART
      3TC). Previous studies from certain developed countries have shown that, in ART
      3TC, 3TC-resistant HBV progressively emerges at an annual rate of 15-20% in
      patients coinfected with HIV-1 and HBV. This scenario in China warrants
      investigation because >10% of all HIV-infected patients in China are HBV
      carriers. We measured the occurrence of 3TC-resistant HBV during ART-3TC for HIV
      HBV coinfection and also tested the effect of tenofovir disoproxil fumarate (TDF)
      used as an additional RTI (ART-3TC/TDF) in a cohort study in China. We obtained
      200 plasma samples collected from 50 Chinese patients coinfected with HIV-1 and
      HBV (positive for hepatitis B surface antigen) and examined them for the
      prevalence of 3TC-resistant HBV by directly sequencing PCR products that covered
      the HBV reverse-transcriptase gene. We divided the patients into ART-3TC and ART
      3TC/TDF groups and compared the efficacy of treatment and incidence of drug
      resistance mutation between the groups. HIV RNA and HBV DNA loads drastically
      decreased in both ART-3TC and ART-3TC/TDF groups. In the ART-3TC group, HBV
      breakthrough or insufficient suppression of HBV DNA loads was observed in 20%
      (10/50) of the patients after 96-week treatment, and 8 of these patients harbored
      3TC-resistant mutants. By contrast, neither HBV breakthrough nor treatment
      failure was recorded in the ART-3TC/TDF group. All of the 3TC-resistant HBV
      mutants emerged from the cases in which HBV DNA loads were high at baseline. Our
      results clearly demonstrated that ART-3TC is associated with the emergence of 3TC
      resistant HBV in patients coinfected with HIV-1 and HBV and that ART-3TC/TDF
      reduces HBV DNA loads to an undetectable level. These findings support the use of
      TDF-based treatment regimens for patients coinfected with HIV-1 and HBV. 

PMID- 26288095
TI  - Facilitated subcutaneous immunoglobulin (fSCIg) therapy--practical
      considerations.
AB  - There is an increasing range of therapeutic options for primary antibody
      deficient patients who require replacement immunoglobulin. These include
      intravenous immunoglobulin (IVIg), subcutaneous immunoglobulin (SCIg), rapid push
      SCIg and most recently recombinant human hyaluronidase-facilitated SCIg (fSCIg).
      Advantages of fSCIg include fewer needle punctures, longer infusion intervals and
      an improved adverse effect profile relative to IVIg. Limited real-life experience
      exists concerning the practical aspects of switching or starting patients on
      fSCIg. We describe the first 14 patients who have been treated with fSCIg at the
      Immunodeficiency Centre for Wales (ICW), representing more than 6 patient-years
      of experience. The regimen was well tolerated, with high levels of satisfaction
      and no increase in training requirement, including for a treatment-naive patient.
      Two patients discontinued fSCIg due to pain and swelling at the infusion site,
      and one paused therapy following post-infusion migraines. Ultrasound imaging of
      paired conventional and facilitated SCIg demonstrated clear differences in
      subcutaneous space distribution associated with a 10-fold increase in rate and
      volume delivery with fSCIg. Patient profiles for those choosing fSCIg fell into
      two main categories: those experiencing clinical problems with their current
      treatment and those seeking greater convenience and flexibility. When introducing
      fSCIg, consideration of the type and programming of infusion pump, needle gauge
      and length, infusion site, up-dosing schedule, home training and patient
      information are important, as these may differ from conventional SCIg. This paper
      provides guidance on practical aspects of the administration, training and
      outcomes to help inform decision-making for this new treatment modality.

PMID- 26288094
TI  - Guanabenz Treatment Accelerates Disease in a Mutant SOD1 Mouse Model of ALS.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease
      characterized by loss of motor neurons. The mechanisms leading to motor neuron
      degeneration in ALS are unclear. However, there is evidence for involvement of
      endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in ALS,
      notably in mutant SOD1 mediated models of ALS. Stress induced phosphorylation of
      the eIF2 alpha subunit by eukaryotic translation initiation factor 2-alpha kinase
      3 Perk activates the UPR. Guanabenz is a centrally acting alpha2 adrenergic
      receptor agonist shown to interact with a regulatory subunit of the protein
      phosphatase, Pp1/Gadd34, and selectively disrupt the dephosphorylation of the
      alpha subunit of eukaryotic initiation factor 2 (eif2alpha). Here we demonstrate
      that guanabenz is protective in fibroblasts expressing G93A mutant SOD1 when they
      are exposed to tunicamycin mediated ER stress. However, in contrast to other
      reports, guanabenz treatment accelerated ALS-like disease progression in a strain
      of mutant SOD1 transgenic ALS mice. This study highlights challenges of
      pharmacological interventions of cellular stress responses in whole animal models
      of ALS. 

PMID- 26288097
TI  - Exposure to Hypoxia at High Altitude (5380 m) for 1 Year Induces Reversible
      Effects on Semen Quality and Serum Reproductive Hormone Levels in Young Male
      Adults.
AB  - This study investigated the effect of hypoxia at high altitude on the semen
      quality and the serum reproductive hormone levels in male adults. A total of 52
      male soldiers were enrolled in this cohort study. They were exposed to hypoxia at
      high altitude (5380 m) for 12 months when undergoing a service. After exposure,
      they were followed up for 6 months. The samples of semen and peripheral blood
      were collected at 1 month before exposure (M0), 6 months of exposure (M6), 12
      months of exposure (M12), and 6 months after exposure (M18). The semen quality
      was assessed with computer-assisted analysis system, and the serum levels of
      reproductive hormones, including prolactin (PRL), luteinizing hormone (LH),
      follicle-stimulating hormone (FSH), and testosterone were analyzed by ELISA.
      Compared with those at M0, total sperm count, sperm density, motility, survival
      rate, and serum levels of LH, PRL and testosterone were significantly decreased,
      whereas the liquefaction time was significantly prolonged and serum FSH level was
      significantly increased at M6 (p<0.05). At M12, total sperm count and sperm
      density increased, whereas sperm motility, survival rate, and the liquefaction
      time further decreased. Sperm velocities, progression ratios, and lateral head
      displacements were also decreased. Serum FSH level decreased while serum LH, PRL,
      and testosterone levels increased. Compared with those at M6, the changes in
      these detected parameters of semen and hormone at M12 were significant (p<0.05).
      At M18, all these detected parameters except testosterone level returned to
      levels comparable to those before exposure. In conclusion, hypoxia at high
      altitude causes adverse effects on semen quality and reproductive hormones, and
      these effects are reversible.

PMID- 26288096
TI  - Rational Therapy of Clostridium difficile Infections.
AB  - BACKGROUND: Clostridium difficile infections (CDI) are increasingly important in
      patients with antibiotic treatments, ranging from mild, self-limiting to severe,
      life-threatening disease. Currently, diagnostic algorithms and treatment
      guidelines are being adapted to novel tests and therapeutic options for recurrent
      CDI. METHODS: A systematic literature search using the terms 'Clostridium
      difficile' and 'treatment' was carried out. Current guidelines are being
      discussed from a clinical point of view. RESULTS: State-of-the-art diagnostics
      for C. difficile diagnosis rely on the patient's history, clinical symptoms, and
      laboratory examination of stool. Recommendations are in favour of glutamate
      dehydrogenase (GDH) screening tests and confirmatory detection of C. difficile
      toxin genes (polymerase chain reaction (PCR)). Therapeutic strategies depend on
      disease severity (mild vs. severe) and endorse metronidazole and vancomycin as
      well as fidaxomycin for recurrent disease. In very severe cases, surgical therapy
      is recommended. For relapsing diseases, faecal transfer is considered as a
      therapeutic option if available. CONCLUSION: Current guidelines have been adapted
      to new pathways in diagnosing CDI and have included statements on novel
      therapeutic options such as fidaxomycin and faecal transplant for recurrent
      disease. Depending on the severity of the disease, standard therapy with either
      metronidazole or vancomycin is recommended.

PMID- 26288098
TI  - Does Disclosure of Terminal Prognosis Mean Losing Hope? Insights from Exploring
      Patient Perspectives on Their Experience of Palliative Care Consultations.
AB  - BACKGROUND: A primary barrier to physician disclosure of terminal prognosis is
      concern that patients will lose hope. Inpatient palliative care (IPC) teams are
      especially posed to mediate this barrier, but little is known about patient
      perceptions and experience of IPC. OBJECTIVE: This study aimed to elicit
      seriously ill patients' perspective and experience of an IPC consultation, and to
      explore patient attitudes toward information derived from the consultation.
      METHODS: An exploratory, qualitative study was conducted at a large nonprofit
      community hospital in the Los Angeles area. An established IPC team conducted
      individualized consults with patients and families within 24 hours of referral.
      Eligible participants were English-speaking adults, aged 18 or over, who had
      received an IPC consultation within the previous week during their
      hospitalization. Purposive recruitment of patients was conducted by the IPC
      social worker. Interviews were conducted at bedside using a semistructured
      interview protocol employing open-ended questions. RESULTS: Twelve seriously ill
      patients were interviewed. Four themes were identified from the interview
      transcripts: (1) holistic care approach, (2) knowledge/information gained, (3)
      hope and enlightenment, and (4) patient readiness. CONCLUSIONS: Results suggest
      that disclosure of a terminal prognosis does not mean loss of patient hope.
      Instead, hope was redefined on a goal other than cure. Presenting patients with
      information and increasing their knowledge about care options and resources may
      facilitate patients in identifying meaningful goals that are better aligned with
      their prognosis.

PMID- 26288099
TI  - Extreme variation in patterns of tandem repeats in mitochondrial control region
      of yellow-browed tits (Sylviparus modestus, Paridae).
AB  - To investigate the evolutionary pattern and origins of tandem repeats in the
      mitochondrial control region of the yellow-browed tit (Sylviparus modestus), the
      control region and another four mitochondrial loci from fifteen individuals were
      analyzed. A 117-bp tandem repeat unit that repeated once, twice or three times in
      different individuals was found, and a rarely reported arrangement for this
      tandem repeats region that a 5' imperfect copy at its downstream and a 3'
      imperfect copy at its upstream was observed. The haplotype network, phylogenetic
      trees, and ancestral state reconstruction of the combined dataset of five loci
      suggested multiple origins of the same repeat number. The turnover model via
      slipped-strand mispairing was introduced to interpret the results, because
      mispairing occurred so frequently that multiple origins of certain repeat number
      were observed. Insertion via recombination should be a better explanation for the
      origin of this tandem repeat unit, considering characteristics of the combined
      sequence of the 3' and 5' imperfect copy, including identification of its homolog
      in other passerines and its predicted secondary structure. 

PMID- 26288100
TI  - Can anti-Mullerian hormone (AMH) predict the outcome of intrauterine insemination
      with controlled ovarian stimulation?
AB  - OBJECTIVE: To assess whether the levels of anti-Mullerian hormone (AMH) are
      related to outcome of intrauterine insemination (IUI) in patients treated with
      gonadotropins. INTERVENTION(S): A total of 195 patients underwent controlled
      ovarian stimulation (COS) with recombinant follicle stimulating hormone (rFSH)
      (50-150 IU/d). All patients were submitted upto three cycles of IUI. OUTCOME:
      Primary outcome was the ability of AMH levels to predict clinical pregnancy at
      first attempt and the cumulative clinical pregnancy probability of upto three IUI
      cycles. Secondary outcomes were the relation of AMH, LH, FSH, BMI, age, parity
      and basic estradiol levels with each other and the outcome of IUI. RESULTS: The
      area under the receiver operating characteristic (ROC) curve in predicting
      clinical pregnancy for AMH at first attempt was 0.53 and for cumulative clinical
      pregnancy was 0.76. AMH levels were positively correlated with clinical pregnancy
      rate at first attempt and with cumulative clinical pregnancy rate, but negatively
      correlated with patient's age and FSH levels. Patient's FSH, LH levels were
      negatively correlated with cumulative clinical pregnancy rate. CONCLUSIONS: AMH
      levels seem to have a positive correlation and patient's age and LH levels had a
      negative correlation with the outcome of IUI and COS with gonadotropins. AMH
      concentration was significantly higher and LH was significantly lower in patients
      with a clinical pregnancy after three cycles of IUI treatment compared with those
      who did not achieve pregnancy.

PMID- 26288101
TI  - Effects of intradialytic exercise on systemic cytokine in patients with chronic
      kidney disease.
AB  - BACKGROUND: Immunological dysfunctions and a pro-inflammatory environment are
      associated with higher risk of cardiovascular diseases in chronic kidney disease
      (CKD). Physical exercise can be an important anti-inflammatory strategy, but the
      effects in CKD remain poorly investigated. OBJECTIVE: Evaluate the acute
      inflammatory response to intradialytic exercise in the peripheral blood of
      individuals with CKD. METHODS: Nine patients, of both genders, with CKD and
      allocated in the ambulatory of hemodialysis of Hospital Ernesto Dornelles
      (Brazil), performed two sessions of hemodialysis (HD) in random form: aerobic
      intradialytic exercise sessions (EX, 20 min of moderate exercise in cycle
      ergometer) and a control hemodialysis session (CON). Peripheral blood collection
      was made at the baseline, during and immediately after HD to evaluate the
      cytokine profile: interleukin-6, interleukin-10 (IL-10), interleukin-17a (IL
      17a), interferon-gamma (INF-gamma) and tumoral necrosis factor-alpha (TNF-alpha).
      RESULTS: INF-gamma decreased during HD when compared with the pre moment in both
      sessions, while an increase in post HD was only found in the CON session. IL-17
      was higher in post when compared with during HD in both sessions. In addition to
      the time effect, IL-10 presented a time * group interaction and the relative
      changes were significantly higher in EX when compared with the CON session. The
      relative changes in TNF-alpha tended to be higher in CON when compared with EX
      immediately post HD session. CONCLUSIONS: These data indicate that 20 min of
      intradialytic exercise have modest effect in systemic inflammation. However, the
      significant increase in IL-10 may indicate an immunoregulatory effect of physical
      exercise.

PMID- 26288102
TI  - Optimum study design for detecting imprinting and maternal effects based on
      partial likelihood.
AB  - Despite spectacular advances in molecular genomic technologies in the past two
      decades, resources available for genomic studies are still finite and limited,
      especially for family-based studies. Hence, it is important to consider an
      optimum study design to maximally utilize limited resources to increase
      statistical power in family-based studies. A particular question of interest is
      whether it is more profitable to genotype siblings of probands or to recruit more
      independent families. Numerous studies have attempted to address this study
      design issue for simultaneous detection of imprinting and maternal effects, two
      important epigenetic factors for studying complex diseases. The question is far
      from settled, however, mainly due to the fact that results and recommendations in
      the literature are based on anecdotal evidence from limited simulation studies
      rather than based on rigorous statistical analysis. In this article, we propose a
      systematic approach to study various designs based on a partial likelihood
      formulation. We derive the asymptotic properties and obtain formulas for
      computing the information contents of study designs being considered. Our results
      show that, for a common disease, recruiting additional siblings is beneficial
      because both affected and unaffected individuals will be included. However, if a
      disease is rare, then any additional siblings recruited are most likely to be
      unaffected, thus contributing little additional information; in such cases,
      additional families will be a better choice with a fixed amount of resources. Our
      work thus offers a practical strategy for investigators to select the optimum
      study design within a case-control family scheme before data collection. 

PMID- 26288104
TI  - Predictors of depression among patients on art in a rural health district in
      North West Cameroon.
AB  - Depression in people living with HIV/AIDS (acquired immune-deficiency syndrome)
      (PLWHA) increases risky HIV transmission behaviour, disease progression to AIDS,
      negatively affects drug adherence and is thus a risk for the development of drug
      resistant strains. This study sought to identify predictors of depression in
      rural Cameroon. A cross-sectional analytic study was carried out from September
      2013 to November 2013 in the Mbengwi district hospital of the North West region.
      We measured depression (PHQ-9 (nine-item Patient Health Questionnaire)), clinical
      and demographic characteristics of patients on antiretroviral therapy (ART).
      Means, proportions and a stepwise logistic regression model were fit to describe
      participants' characteristics and predictors of depression in the study
      population. Of the 202 recruited patients, 58(28.7%) had a positive depression
      screen. Independent predictors of depression included monthly income less than
      20,000 FCFA (US$40), (adjusted odds ratio (aOR) = 2.47; 95% CI = 1.18-5.18), CD4
      count <200 cls/ul (aOR = 7.56; 95% CI = 2.46-23.30) and presence of AIDS symptoms
      (aOR = 4.29; 95% CI = 2.09-8.81). There was no significant correlation between
      duration on ART, marital status, age, gender and depression. Early diagnosis and
      treatment of depressed patients need to be incorporated into intervention
      programmes, which might improve patient outcomes. More research is needed to
      investigate the impact of antidepressant therapy in PLWHA on the evolution of
      treatment.

PMID- 26288107
TI  - Errors in the Author Affiliations and Corresponding Author Address. Survival
      Benefit of Breast Surgery for Low-Grade Ductal Carcinoma In Situ: A Population
      Based Cohort Study.

PMID- 26288108
TI  - Error in Reference Numbering. beta-Blockade and Operative Mortality in Noncardiac
      Surgery: Harmful or Helpful?

PMID- 26288110
TI  - SUBRETINAL NEOVASCULARIZATION IN MACULAR TELANGIECTASIA TYPE 2: OPTICAL COHERENCE
      TOMOGRAPHIC ANGIOGRAPHY AND TREATMENT RESPONSE.
AB  - PURPOSE: To report the optical coherence tomographic angiography findings and
      response to treatment in a case of macular telangiectasia Type 2 with subretinal
      neovascularization. METHODS: Case report. RESULTS: A 64-year-old man with macular
      telangiectasia Type 2 developed subretinal neovascularization, which was imaged
      on optical coherence tomographic angiography. He was treated with intravitreal
      aflibercept, and there was a remarkable reduction of flow in the subretinal
      neovascular network on optical coherence tomographic angiography. CONCLUSION:
      Optical coherence tomographic angiography provides detailed information on the
      retinal microvasculature and subretinal neovascularization in macular
      telangiectasia Type 2. It can be used to assess response to treatment.

PMID- 26288109
TI  - Residual exhaled nitric oxide elevation in asthmatics is associated with
      eosinophilic chronic rhinosinusitis.
AB  - OBJECTIVE: Eosinophilic chronic rhinosinusitis (ECRS) is as a subgroup of chronic
      rhinosinusitis (CRS) with nasal polyps. ECRS is a refractory disease closely
      related to bronchial asthma. Fractionated exhaled nitric oxide (FeNO) levels were
      reportedly elevated in some asthmatics with CRS after adequate treatment,
      suggesting that residual eosinophilic airway inflammation or ECRS might affect
      FeNO levels. METHODS: To investigate the association between asthma with ECRS and
      FeNO levels, we examined FeNO levels in 133 asthmatics (99 with ECRS and 34
      without ECRS) and 13 patients with ECRS without asthma. The severity of asthma
      was defined by the Global Initiative for Asthma guidelines and that of sinusitis
      was evaluated by the sinus CT score based on the Lund-Mackay scale. RESULTS AND
      CONCLUSIONS: FeNO levels were elevated even in well-controlled asthmatics with
      ECRS, whereas asthmatics without ECRS and ECRS patients without asthma did not
      have high FeNO levels (>50 ppb). Although FeNO levels were not correlated with
      asthma severity, they were positively correlated with the sinus CT score. In
      asthmatics with ECRS, patients with higher FeNO levels had more severe ECRS and
      asthma. There is a possibility of having comorbid ECRS, particularly in
      asthmatics with high FeNO levels even after adequate treatment, including ICS,
      suggesting that asthma and ECRS may be closely associated as one airway disease
      with eosinophilic inflammation. Continual awareness of the coexistent ECRS is
      ideally recommended for asthmatics with high FeNO levels.

PMID- 26288111
TI  - Structure-Activity Relationships and Anti-inflammatory Activities of N
      Carbamothioylformamide Analogues as MIF Tautomerase Inhibitors.
AB  - Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, is an
      attractive therapeutic target for the treatment of inflammatory diseases. In our
      previous study, 3-[(biphenyl-4-ylcarbonyl)carbamothioyl]amino benzoic acid
      (compound 1) was discovered as a potent inhibitor of MIF by docking-based virtual
      screening and bioassays. Here, a series of analogues of compound 1 derived from
      similarity search and chemical synthesis were evaluated for their MIF tautomerase
      activities, and their structure-activity relationships were then analyzed. The
      most potent inhibitor (compound 5) with an IC50 of 370 nM strongly suppressed
      lipopolysaccharide (LPS)-induced production of TNF-alpha and IL-6 in a dose
      dependent manner and significantly enhanced the survival rate of mice with LPS
      induced endotoxic shock from 0 to 35% at 0.5 mg/kg and to 45% at 1 mg/kg,
      highlighting the therapeutic potential of the MIF tautomerase inhibition in
      inflammatory diseases. 

PMID- 26288112
TI  - Current trends and investigative developments in wheat allergy.
AB  - The prevalence of gluten-related diseases is increasing in an alarming rate. The
      studies regarding wheat allergy in the Southeastern and Central Europe are few.
      The aim of our study was to discuss the effectiveness of serological tests in
      detecting the prevalence of specific allergens. 

PMID- 26288113
TI  - Seroprevalence of Leishmania infection among asymptomatic renal transplant
      recipients from southern Spain.
AB  - BACKGROUND: The aim of this article is to assess the seroprevalence of Leishmania
      infection among asymptomatic renal transplant recipients in a population in the
      south of Spain. METHODS: Serum samples were screened for immunoglobulin-G
      antibodies against Leishmania with an indirect fluorescent antibody test.
      RESULTS: Of 625 examined serum samples, 30 (4.8%) samples were positive for
      Leishmania antibodies. Thirteen samples showed titers of 1:80, 15 samples showed
      titers of 1:160, and 2 samples showed titers of 1:320. None of the patients with
      positive serology to Leishmania showed signs or symptoms compatible with
      leishmaniasis. CONCLUSION: The prevalence of Leishmania infection found among
      asymptomatic renal transplant patients reinforces the need for attention in
      evaluation of these patients in endemic areas.

PMID- 26288114
TI  - RG7112, a small-molecule inhibitor of MDM2, enhances trabectedin response in soft
      tissue sarcomas.
AB  - MDM2 is a critical negative regulator of the p53 tumor suppressor protein.
      Selected sarcoma subtypes are being treated with Trabectedin in second line,
      which promotes DNA damage and p53-dependent apoptosis. The aim of this study was
      to evaluate the improvement of Trabectedin response with MDM2 inhibitors in soft
      tissue sarcomas. The antitumor effects of Trabectedin, Nutlin-3A and RG7112 as
      single agents or in combination were examined in vitro. RG7112 significantly
      synergized with Trabectedin in MDM2-amplified liposarcoma cells, representing a
      promising new therapeutic strategy for the treatment of sarcomas with MDM2
      amplification. 

PMID- 26288115
TI  - Claudin 1 promotes migration and increases sensitivity to tamoxifen and
      anticancer drugs in luminal-like human breast cancer cells MCF7.
AB  - Downregulation of claudin 1, a critical tight junction protein, has been
      correlated with increased invasiveness in breast cancer. However, recent studies
      suggest that claudin 1 contributes to the progression of some molecular subtypes
      of breast cancer. In this study, claudin 1 promotes migration in luminal-like
      MCF7 human breast cancer cells and increases their sensitivity to tamoxifen,
      etoposide, and cisplatin. We also observed an inverse relationship between
      upregulation of claudin 1 and TGFbeta. Collectively, our results suggest that
      claudin 1 has the potential to be used as a predictive marker for treatment
      efficacy for specific breast cancer patient subgroups. 

PMID- 26288116
TI  - BCR-ABL mutations in chronic myeloid leukemia treated with tyrosine kinase
      inhibitors and impact on survival.
AB  - This is the largest Latin American study of BCR-ABL mutations in chronic myeloid
      leukemia (CML) patients, resistant to imatinib (IM). In 195/467 (41%) patients,
      mutations were detected. The most frequent mutation was T315I (n = 31, 16%).
      Progression-free (PFS) and overall survival (OS) at 5 years were lower in
      patients with BCR-ABL mutations (43% vs. 65%, p = 0.07 and 47% vs. 72%, p = 0.03,
      respectively) and in those with the T315I mutation (p = 0.003 and p = 0.03). OS
      and PFS were superior in subgroup who switched to second generation inhibitors
      (SGIs) after IM failure (OS: 50% vs. 39% p = 0.01; PFS: 48% vs. 30% p = 0.02).
      BCR-ABL mutations conferred a significant poor prognosis in CML patients. 

PMID- 26288117
TI  - The complete mitochondrial genome sequence of Symphysodon discus Heckel (1840).
AB  - The complete mitochondrial genome of Symphysodon discus Heckel was 16 544 bp in
      length, consisting of 22 tRNA genes, 13 protein-coding genes, 2 ribosomal rRNA
      genes, and a control region or displacement loop (D-loop). With the exception of
      8 tRNAs and ND6 genes, the others were encoded on H-strand. The base composition
      on H-strand was 30.04% C, 28.39% A, 26.49% T and 15.07% G, exhibiting an A + T
      rich pattern. The codon usage was consistent with the other vertebrate
      mitochondrial pattern, i.e. start codon is ATG or GTG and stop codons are TAA,
      TAG or T- -. Stop codon TAG was only found in the ND6. There were 8 regions of
      gene overlapped with the length of 26 bp in total and 12 intergenic spacer
      regions (99 bp in total).

PMID- 26288119
TI  - Psychometric properties of the Swedish version of the General Self-Efficacy Scale
      in stroke survivors.
AB  - The aim of this study was to assess the psychometric properties of a Swedish
      version of the General Self-Efficacy Scale (GSE) in stroke survivors. The GSE was
      administered by the same assessor on two occasions 3 weeks apart with 34 stroke
      survivors (21 men, 13 women; mean age=68.1 years) 6-10 months after stroke.
      Psychometric properties including targeting and scaling assumptions, and several
      reliability indices, were calculated. The mean score was well above the midpoint
      of the scale and the total scores spanned almost the entire scale range. Floor
      and ceiling effects were within the limits of 15-20% for total scores (0 and
      8.8%, respectively), but not for each item individually. Total skewness was
      estimated at -1.02 and skewness for individual items was estimated as -1.55 to 
      0.33. The corrected item-total correlations were all above 0.3, except for one
      item. Cronbach's alpha was high (0.92) and the test-retest reliability was
      acceptable (intraclass correlation coefficient2,1=0.82). The mean difference (d)
      was -0.68 (NS). The SEM was 2.97 (SEM%; 9.40). In conclusion, although targeting
      in relation to skewness and ceiling effects was observed in some items, the GSE
      was reliable for use in mobile stroke survivors 6-10 months after stroke. 

PMID- 26288118
TI  - Patient-reported outcomes with the beta3 -adrenoceptor agonist mirabegron in a
      phase III trial in patients with overactive bladder.
AB  - AIMS: To assess patient-reported outcomes (PROs) in patients with overactive
      bladder (OAB) receiving the novel beta3 -adrenoceptor agonist mirabegron.
      METHODS: Data from a randomised, double-blind, controlled phase III trial in
      1,987 patients aged >=18 years with OAB symptoms for >=3 months were analysed.
      Patients received placebo, mirabegron 50 or 100 mg/day, or tolterodine extended
      release (ER) 4 mg orally once daily for 12 weeks after a 2-week placebo run-in.
      Prespecified analysis of PROs (changes in OAB Questionnaire [OAB-q], Patient
      Perception of Bladder Condition [PPBC], and Work Productivity and Activity
      Impairment: Specific Health Problem [WPAI-SHP] instrument) in patients treated
      with mirabegron 50 mg/day, tolterodine ER 4 mg/day or placebo is reported. Post
      hoc analyses of OAB-q, PPBC and the Treatment Satisfaction-Visual Analogue Scale
      (TS-VAS) in patients who were incontinent at baseline are also reported. RESULTS:
      Significant improvements over placebo in OAB-q coping and concern from baseline
      to final visit were observed with mirabegron 50 mg/day. No significant
      improvements in these parameters were observed with tolterodine ER 4 mg/day.
      Mirabegron 50 mg/day significantly increased the proportion of patients showing a
      PPBC improvement over placebo. Mirabegron 50 mg/day also produced greater
      improvements in WPAI-SHP presenteeism and greater reductions in absenteeism and
      overall work impairment than placebo or tolterodine ER 4 mg/day. The impact of
      mirabegron 50 mg/day treatment on PROs in the incontinent population appears to
      be greater than that in the overall OAB population. CONCLUSIONS: At the approved
      dose of 50 mg/day, mirabegron significantly improves OAB patients' perception of
      disease and quality of life, independent of whether they are incontinent at
      baseline. Neurourol. Urodynam. 35:987-994, 2016. (c) 2015 The Authors.
      Neurourology and Urodynamics published by Wiley Periodicals, Inc.

PMID- 26288120
TI  - Feasibility and efficacy of high-speed gait training with a voluntary driven
      exoskeleton robot for gait and balance dysfunction in patients with chronic
      stroke: nonrandomized pilot study with concurrent control.
AB  - The aim of this pilot study was to investigate the feasibility of high-speed gait
      training with an exoskeleton robot hybrid assistive limb (HAL) in patients with
      chronic stroke, and to examine the efficacy of eight sessions (8 weeks) of gait
      training with a HAL compared with conventional physical therapy. Eighteen
      patients with chronic stroke were included in this study (nine each in the HAL
      and control groups). The HAL group underwent high-speed gait training with the
      HAL once a week for 8 weeks (20 min/session). The control group underwent
      conventional physical therapy for gait disturbance. Outcome measures were walking
      speed, number of steps, and cadence during a 10 m walking test, a timed up and go
      test, a functional reach test, and the Berg Balance Scale. Assessments were
      performed in the absence of the HAL before training and after the fourth and
      eighth training sessions. All patients in the HAL group completed the high-speed
      gait training without adverse events. The HAL group improved significantly in
      walking speed (55.9% increase, P<0.001), number of steps (17.6% decrease,
      P<0.01), and cadence (32.8% increase, P<0.001) during the 10 m walking test. The
      patients also exhibited significant improvements in the timed up and go test, the
      functional reach test, and the Berg Balance Scale after HAL training (P<0.01 in
      all). No statistical time-dependent changes were observed in any parameter in the
      control group. For chronic stroke patients, high-speed gait training with a HAL
      appears to be feasible and effective in improving gait and balance dysfunction
      despite the limitations of this nonrandomized pilot study. 

PMID- 26288121
TI  - Change in agreement between stroke survivors and their significant others on the
      severity of restrictions of functioning in a 1-year follow-up.
AB  - The aim of this study was to assess the agreement between stroke survivors and
      their significant others on the severity of restrictions of functioning and to
      investigate the change in this agreement in a 1-year follow-up. The 41 stroke
      survivors and their significant others assessed the severity of impairment at the
      end of in-patient interdisciplinary neurorehabilitation and 1 year later using a
      structured form based on International Classification of Functioning, Disability
      and Health (ICF). The main outcomes were as follows: (i) change in the severity
      score of each observer on a particular restriction (intraobserver change); (ii)
      change in difference in severity scores within each observer pair (interobserver
      change); and (iii) change in agreement between interobserver differences in
      severity scores during a 1-year follow-up. The significant others identified more
      restrictions at baseline (256 vs. 194 ICF categories, chi2 P=0.004) than the
      rehabilitants did. After 1 year, this difference became insignificant (218 vs.
      207 ICF categories, chi2 P=0.59). The severity of perceived restrictions did not
      differ over time (all P>0.05). Although significant others rated the restrictions
      as slightly more severe than rehabilitants, the difference was not significant.
      The agreement between severity scores within observer pairs showed a tendency to
      improve during a 1-year follow-up. Statistically significant improvements in
      Cohen's kappa agreement were found for muscle power (0.6-1.0), walking (0.7-0.9),
      eating (0.7-1.0) and immediate family support (0.5-0.8). The agreement between
      stroke survivors and their significant others on the severity of the restrictions
      of functioning showed a tendency to improve over time.

PMID- 26288123
TI  - High Charge-Carrier Mobility of 2.5 cm(2) V(-1) s(-1) from a Water-Borne Colloid
      of a Polymeric Semiconductor via Smart Surfactant Engineering.
AB  - Semiconducting polymer nanoparticles dispersed in water are synthesized by a
      novel method utilizing non-ionic surfactants. By developing a smart surfactant
      engineering technique involving a selective post-removal process of surfactants,
      an unprecedentedly high mobility of 2.51 cm(2) V(-1) s(-1) from a water-borne
      colloid is demonstrated for the first time. 

PMID- 26288122
TI  - Predicting length of stay and conversion to open cholecystectomy for acute
      cholecystitis using the 2013 Tokyo Guidelines in a US population.
AB  - BACKGROUND: The 2013 Tokyo Guidelines (TG13) for acute cholecystitis have not
      been studied extensively in US populations. METHODS: A retrospective review of
      patients with acute cholecystitis within a single system from 2009 to 2013 was
      performed. The diagnosis and severity of acute cholecystitis were assigned by the
      TG13. The primary outcome measures were length of stay and conversion to open
      cholecystectomy. RESULTS: Four hundred and forty-five patients with acute
      cholecystitis were studied. For all patients, length of stay (P < 0.001),
      disposition to home (P < 0.001), and morbidity (P = 0.003) were related to
      increasing TG13 grade. For surgical patients (n = 256), worsened outcomes with
      increasing TG13 grade were seen for conversion to open (P = 0.001), operative
      duration (P < 0.001), length of stay (P < 0.001), disposition to home (P <
      0.001), and readmission (P = 0.037). On multivariate analysis, TG13 grade was an
      independent predictor of increasing length of stay (P = 0.009) and conversion to
      open surgery (grade 2: OR 7.63 (2.25-25.90), grade 3: OR 24.2 (5.0-116.37)).
      CONCLUSIONS: Wide adoption of the TG13 in the US can better inform patients,
      hospital systems, and payers of the expected outcomes of acute cholecystitis.

PMID- 26288124
TI  - Validation of the Caprini Venous Thromboembolism Risk Assessment Model in
      Critically Ill Surgical Patients.
AB  - IMPORTANCE: Appropriate risk stratification for venous thromboembolism (VTE) is
      essential to providing appropriate thromboprophylaxis and avoiding morbidity and
      mortality. OBJECTIVE: To validate the Caprini VTE risk assessment model in a
      previously unstudied high-risk cohort: critically ill surgical patients. DESIGN,
      SETTING, AND PARTICIPANTS: We performed a retrospective cohort study of 4844
      adults (>=18 years old) admitted to a 20-bed surgical intensive care unit in a
      large tertiary care academic hospital during a 5-year period (July 1, 2007,
      through June 30, 2012). MAIN OUTCOMES AND MEASURES: The main study outcome was
      VTE (defined as patients with deep vein thrombosis or pulmonary embolism) that
      occurred during the patient's initial hospital admission. RESULTS: The study
      population was distributed among risk levels as follows: low, 5.3%; moderate,
      19.9%; high, 31.6%; highest, 25.4%; and superhigh, 14.9%. The overall incidence
      of inpatient VTE was 7.5% and increased with risk level: 3.5% in low-risk
      patients, 5.5% in moderate-risk patients, 6.6% in high-risk patients, 8.6% in
      highest-risk patients, and 11.5% in superhigh-risk patients. Patients with
      Caprini scores greater than 8 were significantly more likely to develop inpatient
      VTE events when compared with patients with Caprini scores of 7 to 8 (odds ratio
      [OR], 1.37; 95% CI, 1.02-1.85; P = .04), 5 to 6 (OR, 1.35; 95% CI, 1.16-1.57; P <
      .001), 3 to 4 (OR, 1.30; 95% CI, 1.16-1.47; P < .001), or 0 to 2 (OR, 1.37; 95%
      CI, 1.16-1.64; P < .001). Similarly, patients with Caprini scores of 7 to 8 were
      significantly more likely to develop inpatient VTE when compared with patients
      with Caprini scores of 5 to 6 (OR, 1.33; 95% CI, 1.01-1.75; P = .04), 3 to 4 (OR,
      1.27; 95% CI, 1.08-1.51; P = .005), or 0 to 2 (OR, 1.38; 95% CI, 1.10-1.74; P =
      .006). CONCLUSIONS AND RELEVANCE: The Caprini VTE risk assessment model is valid.
      This study supports the use of individual risk assessment in critically ill
      surgical patients.

PMID- 26288125
TI  - Inhibition of quorum sensing-mediated biofilm formation in Pseudomonas aeruginosa
      by a locally isolated Bacillus cereus.
AB  - Quorum sensing has been shown to play a crucial role in Pseudomonas aeruginosa
      pathogenesis where it activates expression of myriad genes that regulate the
      production of important virulence factors such as biofilm formation. Antagonism
      of quorum sensing is an excellent target for antimicrobial therapy and represents
      a novel approach to combat drug resistance. In this study, Chromobacterium
      violaceum biosensor strain was employed as a fast, sensitive, reliable, and easy
      to use tool for rapid screening of soil samples for Quorum Sensing Inhibitors
      (QSI) and the optimal conditions for maximal QSI production were scrutinized.
      Screening of 127 soil isolates showed that 43 isolates were able to breakdown the
      HHL signal. Out of the 43 isolates, 38 isolates were able to inhibit the violet
      color of the biosensor and to form easily detectable zones of color inhibition
      around their growth. A confirmatory bioassay was carried out after concentrating
      the putative positive cell-free lysates. Three different isolates that belonged
      to Bacillus cereus group were shown to have QSI activities and their QSI
      activities were optimized by changing their culture conditions. Further
      experiments revealed that the cell-free lysates of these isolates were able to
      inhibit biofilm formation by P. aeruginosa clinical isolates. 

PMID- 26288126
TI  - Correction: Spatiotemporal Scan and Age-Period-Cohort Analysis of Hepatitis C
      Virus in Henan, China: 2005-2012.

PMID- 26288127
TI  - Genetic architecture for human aggression: A study of gene-phenotype relationship
      in OMIM.
AB  - Genetic studies of human aggression have mainly focused on known candidate genes
      and pathways regulating serotonin and dopamine signaling and hormonal functions.
      These studies have taught us much about the genetics of human aggression, but no
      genetic locus has yet achieved genome-significance. We here present a review
      based on a paradoxical hypothesis that studies of rare, functional genetic
      variations can lead to a better understanding of the molecular mechanisms
      underlying complex multifactorial disorders such as aggression. We examined all
      aggression phenotypes catalogued in Online Mendelian Inheritance in Man (OMIM),
      an Online Catalog of Human Genes and Genetic Disorders. We identified 95 human
      disorders that have documented aggressive symptoms in at least one individual
      with a well-defined genetic variant. Altogether, we retrieved 86 causal genes.
      Although most of these genes had not been implicated in human aggression by
      previous studies, the most significantly enriched canonical pathways had been
      previously implicated in aggression (e.g., serotonin and dopamine signaling). Our
      findings provide strong evidence to support the causal role of these pathways in
      the pathogenesis of aggression. In addition, the novel genes and pathways we
      identified suggest additional mechanisms underlying the origins of human
      aggression. Genome-wide association studies with very large samples will be
      needed to determine if common variants in these genes are risk factors for
      aggression. (c) 2015 Wiley Periodicals, Inc.

PMID- 26288128
TI  - Mixed-Metal Strategy on Metal-Organic Frameworks (MOFs) for Functionalities
      Expansion: Co Substitution Induces Aerobic Oxidation of Cyclohexene over Inactive
      Ni-MOF-74.
AB  - Different amounts of Co-substituted Ni-MOF-74 have been prepared via a post
      synthetic metal exchange. Inductively coupled plasma mass spectrometry, powder X
      ray diffraction (XRD), N2 adsorption/desorption, and extended X-ray absorption
      fine structure (EXAFS) analyses indicated the successful metathesis between Co
      and Ni in Ni-MOF-74 to form the solid-solution-like mixed-metal Co/Ni-MOF-74. It
      was found that introduction of active Co into the Ni-MOF-74 framework enabled the
      inert Ni-MOF-74 to show activity for cyclohexene oxidation. Since Co was
      favorably substituted at positions more accessible to the substrate, the mixed
      metal Co/Ni-MOF-74 showed superior catalytic performance, compared with pure Co
      MOF-74 containing a similar amount of Co. This study provides a facile method to
      develop solid-solution-like MOFs for heterogeneous catalysis and highlights the
      great potential of this mixed-metal strategy in the development of MOFs with
      specific endowed functionalities. 

PMID- 26288129
TI  - A microfluidic device for rapid quantification of cell-free DNA in patients with
      severe sepsis.
AB  - A rapid and accurate method to identify severe sepsis patients at high risk of
      death is critically needed for clinical practice. In a recent study, the
      concentration of cell-free DNA (cfDNA) in blood was found to be a prognostic
      indicator for ICU mortality in patients with severe sepsis. However, current DNA
      quantification techniques are time-consuming and involve extensive sample
      preparation. In this paper, we demonstrate a low-cost microfluidic device capable
      of rapid quantification of cfDNA in a small droplet (<10 MUl) of blood plasma and
      whole blood in 5 min using only electrical power. The cfDNA in samples is
      selectively labeled by PicoGreen and is extracted and concentrated by
      electrophoresis into a gel by application of a DC potential of 9 V. This device
      has potential as a prognostic tool for early and rapid assessment of septic
      patients. 

PMID- 26288131
TI  - Taking the Operant Paradigm into the Field: Associative Learning in Wild Great
      Tits.
AB  - Associative learning is essential for resource acquisition, predator avoidance
      and reproduction in a wide diversity of species, and is therefore a key target
      for evolutionary and comparative cognition research. Automated operant devices
      can greatly enhance the study of associative learning and yet their use has been
      mainly restricted to laboratory conditions. We developed a portable,
      weatherproof, battery-operated operant device and conducted the first fully
      automated colour-associative learning experiment using free-ranging individuals
      in the wild. We used the device to run a colour discrimination task in a
      monitored population of tits (Paridae). Over two winter months, 80 individuals
      from four species recorded a total of 5,128 trials. Great tits (Parus major) were
      more likely than other species to visit the devices and engage in trials, but
      there were no sex or personality biases in the sample of great tits landing at
      the devices and registering key pecks. Juveniles were more likely than adults to
      visit the devices and to register trials. Individuals that were successful at
      solving a novel technical problem in captivity (lever-pulling) learned faster
      than non-solvers when at the operant devices in the wild, suggesting cross
      contextual consistency in learning performance in very different tasks. There was
      no significant effect of personality or sex on learning rate, but juveniles'
      choice accuracy tended to improve at a faster rate than adults. We discuss how
      customisable automated operant devices, such as the one described here, could
      prove to be a powerful tool in evolutionary ecology studies of cognitive traits,
      especially among inquisitive species such as great tits. 

PMID- 26288130
TI  - Cell-free DNA in Human Follicular Microenvironment: New Prognostic Biomarker to
      Predict in vitro Fertilization Outcomes.
AB  - Cell-free DNA (cfDNA) fragments, detected in blood and in other biological
      fluids, are released from apoptotic and/or necrotic cells. CfDNA is currently
      used as biomarker for the detection of many diseases such as some cancers and
      gynecological and obstetrics disorders. In this study, we investigated if cfDNA
      levels in follicular fluid (FF) samples from in vitro fertilization (IVF)
      patients, could be related to their ovarian reserve status, controlled ovarian
      stimulation (COS) protocols and IVF outcomes. Therefore, 117 FF samples were
      collected from women (n = 117) undergoing IVF/Intra-cytoplasmic sperm injection
      (ICSI) procedure and cfDNA concentration was quantified by ALU-quantitative PCR.
      We found that cfDNA level was significantly higher in FF samples from patients
      with ovarian reserve disorders (low functional ovarian reserve or polycystic
      ovary syndrome) than from patients with normal ovarian reserve (2.7 +/- 2.7
      ng/MUl versus 1.7 +/- 2.3 ng/MUl, respectively, p = 0.03). Likewise, FF cfDNA
      levels were significant more elevated in women who received long ovarian
      stimulation (> 10 days) or high total dose of gonadotropins (>= 3000 IU/l) than
      in women who received short stimulation duration (7-10 days) or total dose of
      gonadotropins < 3000 IU/l (2.4 +/- 2.8 ng/MUl versus 1.5 +/- 1.9 ng/MUl, p =
      0.008; 2.2 +/- 2.3 ng/MUl versus 1.5 +/- 2.1 ng/MUl, p = 0.01, respectively).
      Finally, FF cfDNA level was an independent and significant predictive factor for
      pregnancy outcome (adjusted odds ratio = 0.69 [0.5; 0.96], p = 0.03). In
      multivariate analysis, the Receiving Operator Curve (ROC) analysis showed that
      the performance of FF cfDNA in predicting clinical pregnancy reached 0.73 [0.66
      0.87] with 88% specificity and 60% sensitivity. CfDNA might constitute a
      promising biomarker of follicular micro-environment quality which could be used
      to predict IVF prognosis and to enhance female infertility management. 

PMID- 26288132
TI  - [Circulating vaccine-derived poliovirus type 2 outbreak in Democratic Republic of
      Congo 2011-2012].
AB  - According to the WHO records of 2013, the incidence of poliomyelitis was reduced
      by more than 99%, the number of endemic countries decreased from 125 in 1988 to 3
      in 2013 and over 10 million cases were prevented from poliomyelitis thanks to the
      intensive use of Oral polio vaccine (OPV). However, the emergence of circulating
      vaccine-derived poliovirus strains (cVDPV), causing serious epidemics like the
      wild poliovirus, is a major challenge on the final straight towards the goal of
      eradication and OPV cessation. This paper describes the cVDPVoutbreak that
      occurred in the Democratic Republic of Congo (DRC) from November 2011 to April
      2012. All children under 15 years of age with acute flaccid paralysis (AFP) and
      confirmed presence of cVDPV in the stool samples were included. Thirty (30)
      children, all from the administrative territories of Bukama and Malemba Nkulu in
      the Katanga Province (south-east DRC), were reported. The virus responsible was
      the cVDPV type 2 (0.7% -3.5% divergent from the reference Sabin 2 strain) in 29
      children (97%) and the ambiguous vaccine-derived poliovirus strain (0.7%
      divergent) was confirmed in one case (3%), a boy seventeen months old and already
      vaccinated four times with OPV. Twentyfive children (83%) were protected by any
      of the routine EPI vaccines and 3 children (10%) had never received any dose of
      OPV. In reaction, DRC has conducted five local campaigns over a period of 10
      months (from January to October 2012) and the epidemic was stopped after the
      second round performed in March 2012. As elsewhere in similar conditions, low
      immunization coverage, poor sanitation conditions and the stop of the use of OPV2
      have favoured the emergence of the third cVDPV epidemic in DRC. The
      implementation of the Strategic Plan for Polio eradication and endgame strategic
      plan 2013-2018 will prevent the emergence of cVDPV and set up the conditions for
      a coordinated OPV phase out.

PMID- 26288133
TI  - Phase I study of LY2603618, a CHK1 inhibitor, in combination with gemcitabine in
      Japanese patients with solid tumors.
AB  - This phase I trial evaluated LY2603618, a selective inhibitor of the DNA damage
      checkpoint kinase 1, in combination with gemcitabine. Japanese patients with
      advanced solid tumors were enrolled. All patients received gemcitabine (1000 mg/m
      on days 1, 8, and 15 every 28 days) and either 170 mg (cohort 1) or 230 mg
      (cohort 2) of LY2603618. The primary objective was assessment of
      safety/tolerability. Pharmacokinetic/pharmacodynamic marker profiles were
      secondary objectives. Of the 17 patients enrolled, dose-limiting toxicities were
      observed in one patient in cohort 1 (n=7) and in two patients in cohort 2 (n=10).
      The most common grade 3 or more drug-related treatment-emergent adverse events
      were hematological. Three patients discontinued because of adverse events. Dose
      dependent decreases in LY2603618 exposure were observed, but the LY2603618
      pharmacokinetics at each dose were consistent within and between cycles and did
      not influence gemcitabine pharmacokinetics. Circulating plasma DNA decreased from
      baseline in all four patients who achieved a partial response. Administration of
      170 or 230 mg of LY2603618 following a standard dose of gemcitabine showed
      acceptable safety and tolerability in Japanese patients with solid tumors. 

PMID- 26288134
TI  - N-Farnesyloxy-norcantharimide inhibits progression of human leukemic Jurkat T
      cells through regulation of mitogen-activated protein kinase and interleukin-2
      production.
AB  - This study investigated the anticancer effects of N-farnesyloxy-norcantharimide
      (NOC15), a newly synthesized norcantharidin (NCTD) analogue, on human leukemic
      Jurkat T cells and the signaling pathway underlying its effects. We found that
      the half maximal inhibitory concentration (IC50) of NOC15 on Jurkat T cells is
      1.4 MUmol/l, which is 11.14-fold (=15.6/1.4) smaller than the 15.6 MUmol/l of
      NCTD on Jurkat T cells, whereas the IC50 of NOC15 on human normal lymphoblast
      (HNL) is 207.9 MUmol/l, which is 8.17-fold (=1698.0/207.8) smaller than the
      1698.0 MUmol/l of NCTD on HNL cells. These results indicated that NOC15 exerts a
      higher anticancer effect on Jurkat T cells and has higher toxicity toward HNL
      cells than NCTD. Thus, NOC15 is 1.36-fold (=11.14/8.17) beneficial as an
      anticancer agent toward Jurkat T cells compared with NCTD. Moreover, NOC15 can
      increase the percentage of cells in the sub-G1 phase and reduce the cell
      viability of Jurkat T cells, stimulate p38 and extracellular signal-regulated
      protein kinase 1/2 (ERK1/2) of mitogen-activated protein kinases (MAPKs)
      signaling pathway, and inhibit calcineurin expression and interleukin-2 (IL-2)
      production. However, NOC15 exerted no effects on the Jun-N-terminal kinase 1/2
      (JNK1/2) signaling pathway, the production of IL-8, and tumor necrosis factor
      alpha. We conclude that the anticancer activity of the newly synthesized NOC15 is
      1.36-fold beneficial than NCTD as an anticancer agent and that NOC15 can increase
      the percentage of cells in the sub-G1 phase through the stimulation of p38 and
      ERK1/2 of the MAPK signaling pathway and the inhibition of calcineurin expression
      and IL-2 production. The NOC15 may have the potential of being developed into an
      anticancer agent in the future. 

PMID- 26288137
TI  - [Extreme obesity due to feelings of inner emptiness: structural-developmental
      disorder illustrated by the case of a young morbidly obese patient].
AB  - Structural-developmental disorder, which is characterized by a lack of
      mentalisation, is explained in this article using the case of a morbidly obese 19
      year-old woman. Mentalisation refers to the ability to understand behaviours on
      the basis of mental states such as thoughts, feelings, and desires. Not being
      able to mentalise properly has serious consequences, which became apparent during
      contact with this patient. Although problems with mentalising may not be a
      contraindication for bariatric surgery, substantial follow-up is necessary to
      ensure compliance in the long run. Additionally, knowledge about structural
      developmental disorder may help to decide which kind of interventions may be most
      effective. 

PMID- 26288135
TI  - LXR-Mediated ABCA1 Expression and Function Are Modulated by High Glucose and
      PRMT2.
AB  - High cholesterol and diabetes are major risk factors for atherosclerosis.
      Regression of atherosclerosis is mediated in part by the Liver X Receptor (LXR)
      through the induction of genes involved in cholesterol transport and efflux. In
      the context of diabetes, regression of atherosclerosis is impaired. We proposed
      that changes in glucose levels modulate LXR-dependent gene expression. Using a
      mouse macrophage cell line (RAW 264.7) and primary bone marrow derived
      macrophages (BMDMs) cultured in normal or diabetes relevant high glucose
      conditions we found that high glucose inhibits the LXR-dependent expression of
      ATP-binding cassette transporter A1 (ABCA1), but not ABCG1. To probe for this
      mechanism, we surveyed the expression of a host of chromatin-modifying enzymes
      and found that Protein Arginine Methyltransferase 2 (PRMT2) was reduced in high
      compared to normal glucose conditions. Importantly, ABCA1 expression and ABCA1
      mediated cholesterol efflux were reduced in Prmt2-/- compared to wild type BMDMs.
      Monocytes from diabetic mice also showed decreased expression of Prmt2 compared
      to non-diabetic counterparts. Thus, PRMT2 represents a glucose-sensitive factor
      that plays a role in LXR-mediated ABCA1-dependent cholesterol efflux and lends
      insight to the presence of increased atherosclerosis in diabetic patients. 

PMID- 26288138
TI  - [The quality of patient information brochures can be improved: a discussion using
      radium-223 therapy as an example].
AB  - Patients and their peers need to be adequately informed to ensure proper
      treatment selection, and to facilitate optimal realisation and outcome of
      treatment. Written patient information can contribute, but only when brochures
      are of sufficient quality. An evaluation of patient brochures for radium-223
      therapy in the Netherlands revealed significant differences in the information
      provided, as well as discrepancies between the brochures and national guidelines
      and product documentation. This potentially leads to confusion, false
      expectations, wrong treatment decisions, suboptimal realisation and outcome of
      treatment, and unnecessary toxicity and in radiation hygiene risks. Here we
      discuss the option of national patient information brochures that can be used by
      all centres in order to circumvent such issues. This would require collaboration
      between all medical professions, patient organisations and other groups involved,
      and responsibilities for medical information, distribution and updates must be
      properly defined. A national patient information brochure of this kind is
      currently under development for radium-223 therapy. 

PMID- 26288139
TI  - [A 24-year-old man with chest pain].
AB  - A 24-year-old man was seen with position dependent chest pain and fever.
      Electrocardiography showed typical diffuse repolarisation changes matching with
      perimyocarditis. Local petechiae developed on the left leg and bloodcultures were
      positive for Neisseria meningitidis serogroup C, which provided the diagnosis
      perimyocarditis caused by Neisseria meningitidis. 

PMID- 26288136
TI  - Lipin-1 contributes to modified low-density lipoprotein-elicited macrophage pro
      inflammatory responses.
AB  - Atherosclerosis is a chronic inflammatory disease of large and medium-sized
      arteries and the underlying cause of cardiovascular disease, a major cause of
      mortality worldwide. The over-accumulation of modified cholesterol-containing low
      density lipoproteins (e.g. oxLDL) in the artery wall and the subsequent
      recruitment and activation of macrophages contributes to the development of
      atherosclerosis. The excessive uptake of modified-LDL by macrophages leads to a
      lipid-laden "foamy" phenotype and pro-inflammatory cytokine production. Modified
      LDLs promote foam cell formation in part by stimulating de novo lipid
      biosynthesis. However, it is unknown if lipid biosynthesis directly regulates
      foam cell pro-inflammatory mediator production. Lipin-1, a phosphatidate
      phosphohydrolase required for the generation of diacylglycerol during
      glycerolipid synthesis has recently been demonstrated to contribute to bacterial
      induced pro-inflammatory responses by macrophages. In this study we present
      evidence demonstrating the presence of lipin-1 within macrophages in human
      atherosclerotic plaques. Additionally, reducing lipin-1 levels in macrophages
      significantly inhibits both modified-LDL-induced foam cell formation in vitro, as
      observed by smaller/fewer intracellular lipid inclusions, and ablates modified
      LDL-elicited production of the pro-atherogenic mediators tumor necrosis factor
      alpha, interleukin-6, and prostaglandin E2. These findings demonstrate a critical
      role for lipin-1 in the regulation of macrophage inflammatory responses to
      modified-LDL. These data begin to link the processes of foam cell formation and
      pro-inflammatory cytokine production within macrophages.

PMID- 26288140
TI  - [A new incentive for cardiac rehabilitation].
AB  - Only a minority of patients receive cardiac rehabilitation after acute coronary
      syndrome, coronary bypass grafting or heart valve operation. A recent study
      published in the European Heart Journal, presents the results from approximately
      36,000 patients who participated in a rehabilitation program. It showed a 35%
      reduction in mortality during 4-year follow-up. Modern cardiac rehabilitation
      does not only focus on physical training but also includes interactive education,
      relaxation therapy, coping and self-management. Patients are also encouraged to
      participate in structural physical activity, which is incorporated into their
      daily life after the rehabilitation program. From other studies we know that not
      only is mortality reduced but also quality of life is improved as a result of
      cardiac rehabilitation. We both strongly recommend and encourage our colleagues
      to refer their cardiac patients to a multidisciplinary cardiac rehabilitation
      program.

PMID- 26288141
TI  - Contrasting the Effects of Maternal and Behavioral Characteristics on Fawn Birth
      Mass in White-Tailed Deer.
AB  - Maternal care influences offspring quality and can improve a mother's inclusive
      fitness. However, improved fitness may only occur when offspring quality (i.e.,
      offspring birth mass) persists throughout life and enhances survival and/or
      reproductive success. Although maternal body mass, age, and social rank have been
      shown to influence offspring birth mass, the inter-dependence among these
      variables makes identifying causation problematic. We established that fawn birth
      mass was related to adult body mass for captive male and female white-tailed deer
      (Odocoileus virginianus), thus maternal care should improve offspring fitness. We
      then used path analysis to identify which maternal characteristic(s) most
      influenced fawn birth mass of captive female white-tailed deer. Maternal age,
      body mass and social rank had varying effects on fawn birth mass. Maternal body
      mass displayed the strongest direct effect on fawn birth mass, followed by
      maternal age and social rank. Maternal body mass had a greater effect on social
      rank than age. The direct path between social rank and fawn birth mass may
      indicate dominance as an underlying mechanism. Our results suggest that heavier
      mothers could use dominance to improve access to resources, resulting in
      increased fitness through production of heavier offspring. 

PMID- 26288144
TI  - Successful Control of Carcinoma of Unknown Primary with Axitinib, a Novel
      Molecular-Targeted Agent: A Case Report.
AB  - Carcinoma of unknown primary (CUP) is a common malignancy. In view of the poor
      prognosis of CUP, more effective therapy is needed. A 47-year-old man with CUP
      affecting the bone visited our institution. Treatment with heavy ion
      radiotherapy, cytotoxic chemotherapy, and resection of the bone tumor conferred
      neither control of the tumor nor the patient's symptoms such as tumor fever and
      bone pain. The bone biopsy at hemipelvectomy suggested undifferentiated
      adenocarcinoma with some features of clear cell carcinoma, although no lesions
      were detected in the kidneys. Based on the pathological diagnosis, treatment with
      sunitinib or everolimus was administered but resulted in progressive disease.
      However, axitinib showed favorable effects, controlling tumor progression and
      palliating his symptoms. To our knowledge, this is the first case of successful
      control of CUP with axitinib. 

PMID- 26288142
TI  - Development of Sound Localization Strategies in Children with Bilateral Cochlear
      Implants.
AB  - Localizing sounds in our environment is one of the fundamental perceptual
      abilities that enable humans to communicate, and to remain safe. Because the
      acoustic cues necessary for computing source locations consist of differences
      between the two ears in signal intensity and arrival time, sound localization is
      fairly poor when a single ear is available. In adults who become deaf and are
      fitted with cochlear implants (CIs) sound localization is known to improve when
      bilateral CIs (BiCIs) are used compared to when a single CI is used. The aim of
      the present study was to investigate the emergence of spatial hearing sensitivity
      in children who use BiCIs, with a particular focus on the development of
      behavioral localization patterns when stimuli are presented in free-field
      horizontal acoustic space. A new analysis was implemented to quantify patterns
      observed in children for mapping acoustic space to a spatially relevant
      perceptual representation. Children with normal hearing were found to distribute
      their responses in a manner that demonstrated high spatial sensitivity. In
      contrast, children with BiCIs tended to classify sound source locations to the
      left and right; with increased bilateral hearing experience, they developed a
      perceptual map of space that was better aligned with the acoustic space. The
      results indicate experience-dependent refinement of spatial hearing skills in
      children with CIs. Localization strategies appear to undergo transitions from
      sound source categorization strategies to more fine-grained location
      identification strategies. This may provide evidence for neural plasticity, with
      implications for training of spatial hearing ability in CI users. 

PMID- 26288143
TI  - Catecholaminergic Gene Polymorphisms Are Associated with GI Symptoms and
      Morphological Brain Changes in Irritable Bowel Syndrome.
AB  - BACKGROUND: Genetic and environmental factors contribute to the pathophysiology
      of irritable bowel syndrome (IBS). In particular, early adverse life events
      (EALs) and the catecholaminergic system have been implicated. AIMS: To
      investigate whether catecholaminergic SNPs with or without interacting with EALs
      are associated with: 1) a diagnosis of IBS, 2) IBS symptoms and 3) morphological
      alterations in brain regions associated with somatosensory, viscerosensory, and
      interoceptive processes. METHODS: In 277 IBS and 382 healthy control subjects
      (HCs), 11 SNPs in genes of the catecholaminergic signaling pathway were
      genotyped. A subset (121 IBS, 209 HCs) underwent structural brain imaging
      (magnetic resonance imaging [MRI]). Logistic and linear regressions evaluated
      each SNP separately and their interactions with EALs in predicting IBS and GI
      symptom severity, respectively. General linear models determined grey matter (GM)
      alterations from the SNPs and EALs that were predictive of IBS. RESULTS: 1)
      DIAGNOSIS: There were no statistically significant associations between the SNPs
      and IBS status with or without the interaction with EAL after adjusting for
      multiple comparisons. 2) SYMPTOMS: GI symptom severity was associated with ADRA1D
      rs1556832 (P = 0.010). 3) Brain morphometry: In IBS, the homozygous genotype of
      the major ADRA1D allele was associated with GM increases in somatosensory regions
      (FDR q = 0.022), left precentral gyrus (q = 0.045), and right hippocampus (q =
      0.009). In individuals with increasing sexual abuse scores, the ADRAbeta2 SNP was
      associated with GM changes in the left posterior insula (q = 0.004) and left
      putamen volume (q = 0.029). CONCLUSION: In IBS, catecholaminergic SNPs are
      associated with symptom severity and morphological changes in brain regions
      concerned with sensory processing and modulation and affect regulation. Thus,
      certain adrenergic receptor genes may facilitate or worsen IBS symptoms.

PMID- 26288148
TI  - Correction to: J Womens Health Gend Based Med. 2001 May;10(4):327-334.

PMID- 26288147
TI  - Military Parents' Personal Technology Usage and Interest in e-Health Information
      for Obesity Prevention.
AB  - BACKGROUND: U.S. military families are experiencing high obesity rates similar to
      the civilian population. The Department of Defense's Military Health System (MHS)
      is one of the largest healthcare providers in the United States, serving
      approximately 9.2 million active duty service members, retirees, spouses, and
      children. The annual cost to the MHS for morbidities associated with being
      overweight exceeds $1 billion. The preschool age has been suggested as an
      opportune time to intervene for the prevention of obesity. Thus, this study
      investigated the current level of technology usage by military service member
      families and assessed their needs and interests in health/nutrition information.
      This needs assessment is crucial for researchers/educators to design further
      studies and intervention programs for obesity prevention in military families
      with young children. MATERIALS AND METHODS: In total, 288 military parents (233
      Army and 55 Air Force) at two military bases whose children were enrolled in
      military childcare centers in the southwestern United States participated in a
      Technology Usage in Military Family (TUMF) survey in 2013. RESULTS AND
      CONCLUSIONS: Overall, both bases presented similar technology usage patterns in
      terms of computer and mobile device usage on the Internet. Air Force base parents
      had a slightly higher knowledge level of nutrition/health information than Army
      base parents. The TUMF survey suggested practical ways such as mobile
      applications/Web sites, social networks, games, etc., that health educators can
      use to disseminate nutrition/health information for obesity prevention among
      military families with young children.

PMID- 26288146
TI  - Age-Related Differences in Spatial Frequency Processing during Scene
      Categorization.
AB  - Visual analysis of real-life scenes starts with the parallel extraction of
      different visual elementary features at different spatial frequencies. The global
      shape of the scene is mainly contained in low spatial frequencies (LSF), and the
      edges and borders of objects are mainly contained in high spatial frequencies
      (HSF). The present fMRI study investigates the effect of age on the spatial
      frequency processing in scenes. Young and elderly participants performed a
      categorization task (indoor vs. outdoor) on LSF and HSF scenes. Behavioral
      results revealed performance degradation for elderly participants only when
      categorizing HSF scenes. At the cortical level, young participants exhibited
      retinotopic organization of spatial frequency processing, characterized by medial
      activation in the anterior part of the occipital lobe for LSF scenes (compared to
      HSF), and the lateral activation in the posterior part of the occipital lobe for
      HSF scenes (compared to LSF). Elderly participants showed activation only in the
      anterior part of the occipital lobe for LSF scenes (compared to HSF), but not
      significant activation for HSF (compared to LSF). Furthermore, a ROI analysis
      revealed that the parahippocampal place area, a scene-selective region, was less
      activated for HSF than LSF for elderly participants only. Comparison between
      groups revealed greater activation of the right inferior occipital gyrus in young
      participants than in elderly participants for HSF. Activation of temporo-parietal
      regions was greater in elderly participants irrespective of spatial frequencies.
      The present findings indicate a specific low-contrasted HSF deficit for normal
      elderly people, in association with an occipito-temporal cortex dysfunction, and
      a functional reorganization of the categorization of filtered scenes. 

PMID- 26288145
TI  - The Fecal Virome of Children with Hand, Foot, and Mouth Disease that Tested PCR
      Negative for Pathogenic Enteroviruses.
AB  - Hand, foot, and mouth disease (HFMD) affects infant and young children. A viral
      metagenomic approach was used to identify the eukaryotic viruses in fecal samples
      from 29 Thai children with clinical diagnosis of HFMD collected during the 2012
      outbreak. These children had previously tested negative by PCR for enterovirus 71
      and coxsackievirus A16 and A6. Deep sequencing revealed nine virus families:
      Picornaviridae, Astroviridae, Parvoviridae, Caliciviridae, Paramyxoviridae,
      Adenoviridae, Reoviridae, Picobirnaviridae, and Polyomaviridae. The highest
      number of viral sequences belonged to human rhinovirus C, astrovirus-MLB2, and
      coxsackievirus A21. Our study provides an overview of virus community and
      highlights a broad diversity of viruses found in feces from children with HFMD. 

PMID- 26288149
TI  - Modifying the luteal phase support in natural cycle frozen-thawed embryo transfer
      improves cycle outcome.
AB  - With the recent trend toward single embryo transfer (ET), cryopreservation of
      extraneous embryos is becoming increasingly prevalent. Several replacement
      protocols for frozen-thawed ET (FET) exist, with no advantage of one protocol
      over the others. All consecutive patients undergoing natural cycle Day-3 FET
      cycles between May 2012 and March 2015 in our IVF unit were evaluated. While
      following spontaneous ovulation, all patients received progesterone luteal
      support. Since June 2014, patients underwent the same aforementioned natural
      cycle FET cycles, with two additional injections, one of recombinant hCG (250
      mcg) and the other of GnRH-agonist (triptorelin 0.1 mg), on the day of transfer
      and 4 d later, respectively. While the patients' clinical characteristics, the
      prevalence of embryos that survived the thawing process and the number of embryos
      transferred were comparable between the earlier as compared with the later
      period, implantation rate, positive beta-hCG, clinical, and ongoing pregnancy
      rates were significantly higher during the later period. We, therefore, suggest
      that when natural cycle FET is offered, the addition of two injections of
      recombinant hCG and GnRH-agonist, on the day of transfer and 4 d later,
      respectively, might increase clinical pregancy rates. Further large prospective
      studies are needed to elucidate the aforementioned recommendation prior to its
      routine implementation. 

PMID- 26288150
TI  - Subsampling versus bootstrapping in resampling-based model selection for
      multivariable regression.
AB  - In recent years, increasing attention has been devoted to the problem of the
      stability of multivariable regression models, understood as the resistance of the
      model to small changes in the data on which it has been fitted. Resampling
      techniques, mainly based on the bootstrap, have been developed to address this
      issue. In particular, the approaches based on the idea of "inclusion frequency"
      consider the repeated implementation of a variable selection procedure, for
      example backward elimination, on several bootstrap samples. The analysis of the
      variables selected in each iteration provides useful information on the model
      stability and on the variables' importance. Recent findings, nevertheless, show
      possible pitfalls in the use of the bootstrap, and alternatives such as
      subsampling have begun to be taken into consideration in the literature. Using
      model selection frequencies and variable inclusion frequencies, we empirically
      compare these two different resampling techniques, investigating the effect of
      their use in selected classical model selection procedures for multivariable
      regression. We conduct our investigations by analyzing two real data examples and
      by performing a simulation study. Our results reveal some advantages in using a
      subsampling technique rather than the bootstrap in this context. 

PMID- 26288153
TI  - Application of an ecological framework to examine barriers to the adoption of
      safer conception strategies by HIV-affected couples.
AB  - Safer conception interventions can significantly reduce the risk of horizontal
      HIV transmission between HIV-serodiscordant partners. However, prior to
      implementing safer conception interventions, it is essential to understand
      potential barriers to their adoption so that strategies can be developed to
      overcome these barriers. This paper examines potential barriers to the adoption
      of safer conception strategies by HIV-affected couples in Iringa, Tanzania using
      an ecological framework. We interviewed 30 HIV-positive women, 30 HIV-positive
      men and 30 health providers engaged in delivering HIV-related services. We also
      conducted direct observations at five health facilities. Findings suggest that
      there are multiple barriers to safer conception that operate at the individual,
      relational, environmental, structural, and super-structural levels. The barriers
      to safer conception identified are complex and interact across these levels.
      Barriers at the individual level included antiretroviral adherence, knowledge of
      HIV status, knowledge and acceptability of safer conception strategies, and poor
      nutrition. At the relational level, unplanned pregnancies, non-disclosure of
      status, gendered power dynamics within relationships, and patient-provider
      interactions posed a threat to safer conception. HIV stigma and distance to
      health facilities were environmental barriers to safer conception. At the
      structural level there were multiple barriers to safer conception, including
      limited safer conception policy guidelines for people living with HIV (PLHIV),
      lack of health provider training in safer conception strategies and preconception
      counseling for PLHIV, limited resources, and lack of integration of HIV and
      sexual and reproductive health services. Poverty and gender norms were super
      structural factors that influenced and reinforced barriers to safer conception,
      which influenced and operated across different levels of the framework. Multi
      level interventions are needed to ensure adoption of safer conception strategies
      and reduce the risk of HIV transmission between partners within HIV
      serodiscordant couples. 

PMID- 26288154
TI  - What is needed to make research on the psychosocial work environment and health
      more meaningful? Reflections and missed opportunities in IPD debates.

PMID- 26288152
TI  - The Interplay between Wnt Mediated Expansion and Negative Regulation of Growth
      Promotes Robust Intestinal Crypt Structure and Homeostasis.
AB  - The epithelium of the small intestinal crypt, which has a vital role in
      protecting the underlying tissue from the harsh intestinal environment, is
      completely renewed every 4-5 days by a small pool of stem cells at the base of
      each crypt. How is this renewal controlled and homeostasis maintained,
      particularly given the rapid nature of this process? Here, based on the recent
      observations from in vitro "mini gut" studies, we use a hybrid stochastic model
      of the crypt to investigate how exogenous niche signaling (from Wnt and BMP)
      combines with auto-regulation to promote homeostasis. This model builds on the
      sub-cellular element method to account for the three-dimensional structure of the
      crypt, external regulation by Wnt and BMP, internal regulation by Notch
      signaling, as well as regulation by internally generated diffusible signals.
      Results show that Paneth cell derived Wnt signals, which have been observed
      experimentally to sustain crypts in cultured organs, have a dramatically
      different influence on niche dynamics than does mesenchyme derived Wnt. While
      this signaling can indeed act as a redundant backup to the exogenous gradient, it
      introduces a positive feedback that destabilizes the niche and causes its
      uncontrolled expansion. We find that in this setting, BMP has a critical role in
      constraining this expansion, consistent with observations that its removal leads
      to crypt fission. Further results also point to a new hypothesis for the role of
      Ephrin mediated motility of Paneth cells, specifically that it is required to
      constrain niche expansion and maintain the crypt's spatial structure. Combined,
      these provide an alternative view of crypt homeostasis where the niche is in a
      constant state of expansion and the spatial structure of the crypt arises as a
      balance between this expansion and the action of various sources of negative
      regulation that hold it in check. 

PMID- 26288156
TI  - Medical Education Needs to Change.

PMID- 26288155
TI  - Relationships among obesity, physical activity and sedentary behavior in young
      adolescents with and without lifetime asthma.
AB  - OBJECTIVE: To examine the inter-relationships among body mass index (BMI),
      physical activity, sedentary behavior and gender in urban, low-income, primarily
      African American young adolescents with or without lifetime asthma. METHODS: Data
      were collected in 2002-2004 from 626 12-year old adolescents who were children of
      women who participated in the New Mother's Study in Memphis, TN (1990-1991).
      Adolescents with and without asthma were compared on BMI, physical activity and
      sedentary behavior. Multiple linear regression models were used to examine the
      association of asthma, gender and BMI with physical activity and sedentary
      behavior. RESULTS: Complete data were available for 545 adolescents. Eleven
      percent of adolescents had lifetime asthma. Asthma and gender were associated
      with high-intensity physical activity (p < 0.001). Adolescents with asthma
      participated in less physical activity and girls participated less than boys.
      Gender was associated with sedentary behavior (p < 0.001): boys used personal
      computer (pc)/video after school more than girls. Girls with asthma had a higher
      BMI than girls without asthma (p = 0.027). Boys with asthma were less physically
      active than boys without asthma (p < 0.05). CONCLUSIONS: Adolescents with asthma
      are less physically active than those without asthma and girls are less active
      than boys. Clinicians who provide care for adolescents with asthma are encouraged
      to assess physical activity/sedentary behavior and provide guidance that promotes
      active lifestyles. A longitudinal study is needed to shed light on the unique
      contribution of asthma separated from the effects of overweight/obesity on
      physical activity and sedentary behaviors.

PMID- 26288157
TI  - Improvements in Pinning Fixation for Distal Radius Fractures.
AB  - Despite the increasingly widespread use of the volar plate, the pinning of the
      distal radius keeps its place as a basic technique in the treatment of extra
      articular and intra-articular fractures with dorsal displacement and little
      comminution. To date, there are 2 types of pinning recognized as stable and
      reliable: the "cross-pinning" with 2 styloid pins and a dorso-ulnar one and the
      multiple mixed pinning, which is an improved version of the classical technique
      of Kapandji. This article offers a modified technique of mixed multiple pinning:
      the pinning type Fort-de-France, which offers a more stable reduction. However,
      our technique would have to be confirmed by clinical and biomechanical studies. 

PMID- 26288160
TI  - Authors' response re: Shek KL & Dietz H. Letter to the Editor Re: 'Do ultrasound
      findings of levator ani "Avulsion" correlate with anatomical findings: A
      multicenter cadaveric study'.

PMID- 26288159
TI  - Aspergillus thyroiditis: first antemortem case diagnosed by fine-needle
      aspiration culture in a pediatric stem cell transplant patient.
AB  - Aspergillus thyroiditis (AT) has historically been considered a postmortem
      diagnosis in immunocompromised patients; most have disseminated disease. This
      report summarizes the clinical challenge of diagnosing AT. It also highlights the
      value of the early use of thyroid fine-needle aspiration culture and the need for
      a high index of suspicion to reach the final diagnosis before disease
      dissemination. 

PMID- 26288161
TI  - Potential Tuning of Nanoarchitectures Based on Phthalocyanine Nanopillars:
      Construction of Effective Photocurrent Generation Systems.
AB  - Nanopillars composed of a photoresponsive phthalocyanine derivative have been
      conveniently fabricated using a continuous silane coupling reaction on a
      substrate. The chemical potentials of phthalocyanine nanopillars (PNs) are
      precisely controlled by changing the number of phthalocyanine derivatives on the
      substrate. In addition, photocurrent generation efficiencies have been strongly
      influenced by the number of phthalocyanine derivatives. High photocurrent
      conversion cells in a solid state have been obtained by the combination of PNs
      and a fullerene derivative. 

PMID- 26288158
TI  - Rational Design of Orthogonal Multipolar Interactions with Fluorine in Protein
      Ligand Complexes.
AB  - Multipolar interactions involving fluorine and the protein backbone have been
      frequently observed in protein-ligand complexes. Such fluorine-backbone
      interactions may substantially contribute to the high affinity of small molecule
      inhibitors. Here we found that introduction of trifluoromethyl groups into two
      different sites in the thienopyrimidine class of menin-MLL inhibitors
      considerably improved their inhibitory activity. In both cases, trifluoromethyl
      groups are engaged in short interactions with the backbone of menin. In order to
      understand the effect of fluorine, we synthesized a series of analogues by
      systematically changing the number of fluorine atoms, and we determined high
      resolution crystal structures of the complexes with menin. We found that
      introduction of fluorine at favorable geometry for interactions with backbone
      carbonyls may improve the activity of menin-MLL inhibitors as much as 5- to 10
      fold. In order to facilitate the design of multipolar fluorine-backbone
      interactions in protein-ligand complexes, we developed a computational algorithm
      named FMAP, which calculates fluorophilic sites in proximity to the protein
      backbone. We demonstrated that FMAP could be used to rationalize improvement in
      the activity of known protein inhibitors upon introduction of fluorine.
      Furthermore, FMAP may also represent a valuable tool for designing new fluorine
      substitutions and support ligand optimization in drug discovery projects.
      Analysis of the menin-MLL inhibitor complexes revealed that the backbone in
      secondary structures is particularly accessible to the interactions with
      fluorine. Considering that secondary structure elements are frequently exposed at
      protein interfaces, we postulate that multipolar fluorine-backbone interactions
      may represent a particularly attractive approach to improve inhibitors of protein
      protein interactions. 

PMID- 26288162
TI  - Relationship Between Insertion Torque and Resonance Frequency Measurements,
      Performed by Resonance Frequency Analysis, in Micromobility of Dental Implants:
      An In Vitro Study.
AB  - PURPOSE: To evaluate the micromobility of dental implants under occlusal loading
      in relation to stability measurements of resonance frequency analysis and
      insertion torque. MATERIALS AND METHODS: The sample comprised of 24 implants
      inserted in 12 fresh cow ribs. Insertion torque and Osstell implant stability
      quotient (ISQ) measurements were recorded. An "ad hoc" acrylic premolar was made
      on a temporary abutment and screwed to each implant, and a force of 100 N was
      subsequently applied at an angle of 6 degrees. Implant micromotion was measured
      using a Questar microscope with a resolution of 2 MUm and an image analysis
      program. RESULTS: Data show a statistically significant inverse correlation
      between the ISQ values and implant micromotion under a load of 100 N (R = 0.86, P
      < 0.0001). The same relationship is found between insertion torque and implant
      micromotion, although the relationship is linear up to 34 N.cm and becomes
      exponential for higher values (R = 0.78, P < 0.0001). A direct correlation is
      established between insertion torque and ISQ values. CONCLUSION: There is an
      inverse relationship between both ISQ and insertion torque values and implant
      micromotion under a load of 100 N.

PMID- 26288163
TI  - 30-Year Outcomes of Dental Implants Supporting Mandibular Fixed Dental
      Prostheses: A Retrospective Review of 4 Cases.
AB  - PURPOSE: The aim of this study was to present the 30-year outcomes of 28 implants
      supporting mandibular screw-retained fixed dental prostheses (FDPs). MATERIALS
      AND METHODS: Dental charts of the 4 patients were carefully reviewed, and it was
      noticed that they received 28 implants and 5 screw-retained FDPs in 1983 and
      1984. The chief concerns raised by these patients were poor retention of their
      complete dentures and decreased masticatory function at the time of treatment
      planning. Each dental care they received was recorded in the last 30 years.
      Implant survival, radiographic, and prosthodontic examinations were performed.
      RESULTS: No implants were lost after 30 years, giving the implant a survival rate
      of 100%. The average marginal bone level was 2.6 +/- 0.5 mm at the last recall
      appointment. Of the 5 FDPs delivered, 1 needed replacement, indicating a
      prosthesis survival rate of 80%. The patients needed 21 repairs such as
      replacement of denture teeth/gold screws and hard relining, and 19 adjustments
      such as occlusal adjustments and acrylic resin contouring, over 30 years.
      CONCLUSION: This clinical report shows that machined-surface dental implants can
      successfully support screw-retained fixed dental prostheses for over 30 years,
      making dental implants an important dental treatment alternative compared to the
      traditional prosthetic treatment methods.

PMID- 26288164
TI  - Strategy for tuning the photophysical properties of photosensitizers for use in
      photodynamic therapy.
AB  - A novel approach for tuning spectral properties, as well as minimizing
      aggregation, in zinc porphyrin and zinc phthalocyanine-based compounds is
      presented. Particular emphasis is placed on use of these compounds as
      photosensitizers in photodynamic therapy (PDT). To accomplish this aim, a bulky
      hydrophobic cation, trihexyltetradecylphosphonium, is paired with anionic
      porphyrin and phthalocyanine dyes to produce a group of uniform materials based
      on organic salts (GUMBOS) that absorb at longer wavelengths with high molar
      absorptivity and high photostability. Nanoparticles derived from these GUMBOS
      possess positively charged surfaces with high zeta potential values, which are
      highly desirable for PDT. Upon irradiation at longer wavelengths, these GUMBOS
      produced singlet oxygen with greater efficiency as compared to the respective
      parent dyes. 

PMID- 26288165
TI  - Efficacy of preoperative dexamethasone for postoperative nausea and vomiting
      after laparoscopic cholecystectomy: a large-scale, multicenter, randomized,
      double-blind, placebo-controlled trial in Japan.
AB  - BACKGROUND: To assess the efficacy of preoperative dexamethasone for
      postoperative nausea and vomiting (PONV) after laparoscopic cholecystectomy (LC)
      in Japan. METHODS: A total of 270 patients at eight hospitals were randomized to
      receive dexamethasone 8 mg (n = 136) or placebo (n = 134) intravenously before
      LC. The primary endpoint was the degree of PONV and antiemetic requirements
      within 24 h after LC. Secondary endpoints were postoperative complications,
      postoperative hospital stay, and cost of hospital stay. This study was
      registered: UMIN-CTR (UMIN000003841). RESULTS: Within 6 h after LC, 17% (23/136)
      of patients in the dexamethasone group versus 24% (32/134) in the placebo group
      reported nausea (P = 0.3), and 5% (7/136) versus 7% (10/134) reported vomiting (P
      = 0.2). Metoclopramide 10 mg was used 0.09 +/- 0.31 versus 0.14 +/- 0.35 times (P
      = 0.2). From 6 to 24 h, 10% (14/136) versus 13% (17/134) reported nausea (P =
      0.5), and 5% (7/136) versus 5% (7/134) reported vomiting (P = 0.8).
      Metoclopramide was used 0.04 +/- 0.19 versus 0.03 +/- 0.17 times (P = 0.8).
      Postoperative complications and postoperative hospital stay did not differ
      significantly between the two groups, but the cost of hospital stay was slightly
      higher in the dexamethasone group (P < 0.05). CONCLUSIONS: Routine use of
      preoperative dexamethasone for PONV after elective LC in Japan was not shown to
      have a clinical advantage.

PMID- 26288167
TI  - The AJT Report.

PMID- 26288166
TI  - Estimating Mortality Associated With Antipsychotics and Other Psychotropics.

PMID- 26288170
TI  - Abdominal Mass Found in a Liver Transplant Recipient.

PMID- 26288172
TI  - Electrocatalytic Reduction of Carbon Dioxide by Mn(CN)(2,2'-bipyridine)(CO)3: CN
      Coordination Alters Mechanism.
AB  - MnBr(2,2'-bipyridine)(CO)3 is an efficient and selective electrocatalyst for the
      conversion of CO2 to CO. Herein, substitution of the axial bromide for a
      pseudohalogen (CN) is investigated, yielding Mn(CN)(2,2'-bipyridine)(CO)3. This
      replacement shifts the first and second reductions to more negative potentials (
      1.94 and -2.51 V vs Fc/Fc(+), respectively), but imparts quasi-reversibility at
      the first feature. The two-electron, two-proton reduction of CO2 to CO and H2O is
      observed at the potential of the first reduction. Data from IR
      spectroelectrochemistry, cyclic voltammetry, and controlled potential
      electrolysis indicate that this behavior arises from the disproportionation of
      two one-electron-reduced species to generate the catalytically active species.
      Computations using density functional theory are also presented in support of
      this new mechanism. 

PMID- 26288173
TI  - RNA structure: merging chemistry and genomics for a holistic perspective.
AB  - The advent of deep sequencing technology has unexpectedly advanced our structural
      understanding of molecules composed of nucleic acids. A significant amount of
      progress has been made recently extrapolating the chemical methods to probe RNA
      structure into sequencing methods. Herein we review some of the canonical methods
      to analyze RNA structure, and then we outline how these have been used to probe
      the structure of many RNAs in parallel. The key is the transformation of
      structural biology problems into sequencing problems, whereby sequencing power
      can be interpreted to understand nucleic acid proximity, nucleic acid
      conformation, or nucleic acid-protein interactions. Utilizing such technologies
      in this way has the promise to provide novel structural insights into the
      mechanisms that control normal cellular physiology and provide insight into how
      structure could be perturbed in disease. 

PMID- 26288174
TI  - Microfluidic vascularized bone tissue model with hydroxyapatite-incorporated
      extracellular matrix.
AB  - Current in vitro systems mimicking bone tissues fail to fully integrate the three
      dimensional (3D) microvasculature and bone tissue microenvironments, decreasing
      their similarity to in vivo conditions. Here, we propose 3D microvascular
      networks in a hydroxyapatite (HA)-incorporated extracellular matrix (ECM) for
      designing and manipulating a vascularized bone tissue model in a microfluidic
      device. Incorporation of HA of various concentrations resulted in ECM with
      varying mechanical properties. Sprouting angiogenesis was affected by
      mechanically modulated HA-extracellular matrix interactions, generating a model
      of vascularized bone microenvironment. Using this platform, we observed that
      hydroxyapatite enhanced angiogenic properties such as sprout length, sprouting
      speed, sprout number, and lumen diameter. This new platform integrates fibrin ECM
      with the synthetic bone mineral HA to provide in vivo-like microenvironments for
      bone vessel sprouting. 

PMID- 26288175
TI  - Correction: Integrative Omics Analysis of Rheumatoid Arthritis Identifies Non
      Obvious Therapeutic Targets.

PMID- 26288176
TI  - A three-component synthesis of aryl(heteroaryl)acylamides.
AB  - A three-component reaction of azole or azine N-oxides, 1,1-difluorostyrenes and
      amines gives amides of alpha-aryl-alpha-heteroarylacetic or propionic acids. The
      key step is 1,3-dipolar cycloaddition between N-oxide and difluorostyrene leading
      to the acyl fluoride intermediate, which has been identified and characterized by
      NMR spectroscopy. The whole process is an example of selective functionalization
      of C-H bonds in both 5- and 6-membered heterocyclic systems. 

PMID- 26288177
TI  - Wear Potential of Dental Ceramics and its Relationship with Microhardness and
      Coefficient of Friction.
AB  - PURPOSE: To evaluate, by means of pin-on-disk testing, the wear potential of
      different dental ceramic systems as it relates to friction parameters, surface
      finish, and microhardness. MATERIALS AND METHODS: Three groups of different
      ceramic systems (Noritake EX3, Eris, Empress II) with 20 disks each (10 glazed,
      10 polished) were used. Vickers microhardness (Hv) was determined with a 200-g
      load for 30 seconds. Friction coefficients (MU) were determined by pin-on-disk
      testing (5 N load, 600 seconds, and 120 rpm). Wear patterns were assessed by
      scanning electron microscopy (SEM). The results were analyzed using one-way ANOVA
      and Tukey's test, with the significance level set at alpha = 0.05. RESULTS: The
      coefficients of friction were as follows: Noritake EX3 0.28 +/- 0.12 (polished),
      0.33 +/- 0.08 (glazed); Empress II 0.38 +/- 0.08 (polished), 0.45 +/- 0.05
      (glazed); Eris 0.49 +/- 0.05 (polished), 0.49 +/- 0.06 (glazed). Microhardness
      measurements were as follows: Noritake EX3 530.7 +/- 8.7 (polished), 525.9 +/-
      6.2 (glazed); Empress II 534.1 +/- 8 (polished), 534.7 +/- 4.5 (glazed); Eris,
      511.7 +/- 6.5 (polished), 519.5 +/- 4.1 (glazed). The polished and glazed
      Noritake EX3 and polished and glazed Eris specimens showed statistically
      different friction coefficients. SEM image analysis revealed more surface
      changes, such as small cracks and grains peeling off, in glazed ceramics.
      CONCLUSIONS: Wear potential may be related to the coefficient of friction in
      Noritake ceramics, which had a lower coefficient than Eris ceramics. Within-group
      analysis showed no differences in polished or glazed specimens. The differences
      observed were not associated with microhardness.

PMID- 26288178
TI  - Manipulation of tumor metabolism for therapeutic approaches: ovarian cancer
      derived cell lines as a model system.
AB  - BACKGROUND: Malignant transformation of cells is often accompanied by up
      regulation of glycolysis-related enzymes and transporters, as well as a
      distortion of mitochondrial respiration. As a consequence, most malignant tumors
      utilize high amounts of glucose and produce and accumulate high concentrations of
      lactate, even in the presence of oxygen. This phenomenon has been termed 'Warburg
      Effect'. Here, we aimed at resolving the interrelation between tumor metabolism,
      reactive oxygen species, double strand DNA breaks and radio-resistance in ovarian
      cancer-derived cells. METHODS: As a model system two ovarian cancer-derived cell
      lines, OC316 and IGROV-1, and its corresponding xenografts were used. First, the
      metabolic properties of the xenografts were tested to ensure that initial in
      vitro data might later be transferred to in vivo data. In parallel, three
      inhibitors of tumor cell metabolism, 2-deoxy-D-glucose, an inhibitor of
      glycolysis, oxamate, a pyruvate analogue and inhibitor of lactate dehydrogenase,
      and rotenone, a specific inhibitor of mitochondrial electron complex I, were
      tested for their effect on the metabolism and radio-sensitivity of the respective
      ovarian cancer-derived cell lines. RESULTS: We found that all three inhibitors
      tested led to significant changes in the tumor cell energy metabolism at non
      cytotoxic concentrations. Furthermore, we found that inhibition of tumor
      glycolysis by 2-deoxy-D-glucose in combination with rotenone decreased the radio
      resistance at a clinically relevant radiation dose. This apparent radio
      sensitizing effect appears to be based on an increased level of double strand DNA
      breaks 1 h and 24 h after gamma irradiation. Both cancer-derived cell lines
      maintained their metabolic properties, as well as their protein expression
      profiles and levels of reactive oxygen species in xenografts, thus providing a
      suitable model system for further in vivo investigations. CONCLUSION: A
      combination of metabolic inhibitors and reactive oxygen species-generating
      therapies, such as irradiation, may effectively enhance the therapeutic response
      in particularly metabolically highly active (ovarian) tumors.

PMID- 26288181
TI  - Influence of warmth and competence on the promotion of safe in-group selection:
      Stereotype content model and social categorization of faces.
AB  - Categorizing an individual as a friend or foe plays a pivotal role in navigating
      the social world. According to the stereotype content model (SCM), social
      perception relies on two fundamental dimensions, warmth and competence, which
      allow us to process the intentions of others and their ability to enact those
      intentions, respectively. Social cognition research indicates that, in
      categorization tasks, people tend to classify other individuals as more likely to
      belong to the out-group than the in-group (in-group overexclusion effect, IOE)
      when lacking diagnostic information, probably with the aim of protecting in-group
      integrity. Here, we explored the role of warmth and competence in group
      membership decisions by testing 62 participants in a social-categorization task
      consisting of 150 neutral faces. We assessed whether (a) warmth and competence
      ratings could predict the in-group/out-group categorization, and (b) the reliance
      on these two dimensions differed in low-IOE versus high-IOE participants. Data
      showed that high ratings of warmth and competence were necessary to categorize a
      face as in-group. Moreover, while low-IOE participants relied on warmth, high-IOE
      participants relied on competence. This finding suggests that the proneness to
      include/exclude unknown identities in/from one's own in-group is related to
      individual differences in the reliance on SCM social dimensions. Furthermore, the
      primacy of the warmth effect seems not to represent a universal phenomenon
      adopted in the context of social evaluation. 

PMID- 26288180
TI  - Lipopolysaccharide Promotes Choroidal Neovascularization by Up-Regulation of
      CXCR4 and CXCR7 Expression in Choroid Endothelial Cell.
AB  - Stromal cell-derived factor-1 (SDF-1) has been confirmed to participate in the
      formation of choroidal neovascularization (CNV) via its two receptors: CXC
      chemokine receptors 4 (CXCR4) and CXCR7. Previous studies have indicated that the
      activation of Toll-like receptors (TLRs) by lipopolysaccharide (LPS) might
      elevate CXCR4 and/or CXCR7 expression in tumor cells, enhancing the response to
      SDF-1 to promote invasion and cell dissemination. However, the impact of LPS on
      the CXCR4 and CXCR7 expression in endothelial cells and subsequent pathological
      angiogenesis formation remains to be elucidated. The present study shows that LPS
      enhanced the CXCR4 and CXCR7 expression via activation of the TLR4 pathway in
      choroid-retinal endothelial (RF/6A) cells. In addition, the transcriptional
      regulation of CXCR4 and CXCR7 by LPS was found to be mediated by phosphorylation
      of the extracellular signal-related kinase (ERK) 1/2 and activation of nuclear
      factor kappa B (NF-kappaB) signaling pathways, which were blocked by ERK- or NF
      kappaB-specific inhibitors. Furthermore, the increased CXCR4 and CXCR7 expression
      resulted in increased SDF-1-induced RF/6A cells proliferation, migration and tube
      formation. In vivo, LPS-treated rat had significantly higher mRNA levels of CXCR4
      and CXCR7 expression and lager laser-induced CNV area than vehicle-treated rat.
      SDF-1 blockade with a neutralizing antibody attenuated the progression of CNV in
      LPS-treated rat after a single intravitreal injection. Altogether, these results
      demonstrated that LPS might influence CNV formation by enhancing CXCR7 and CXCR7
      expression in endothelial cells, possibly providing a new perspective for the
      treatment of CNV-associated diseases. 

PMID- 26288182
TI  - Sclerostin, Osteocytes, and Chronic Kidney Disease - Mineral Bone Disorder.
AB  - Osteocytes respond to kidney damage by increasing production of secreted factors
      important to bone and mineral metabolism. These circulating proteins include the
      antianabolic factor, sclerostin, and the phosphaturic hormone, fibroblast growth
      factor 23 (FGF23). Elevated sclerostin levels correlate with increased FGF23,
      localized reduction in Wnt/beta-catenin signaling in the skeleton and reduced
      osteoblast differentiation/activity. Decreased Wnt/beta-catenin signaling occurs
      regardless of the overall changes in bone formation rates, suggesting that a
      reduction in the anabolic response may be a common feature of renal bone
      disorders but additional mechanisms may contribute to the diversity of
      osteodystrophy phenotypes. Recent preclinical studies support this hypothesis, as
      treatment with antisclerostin antibodies improved bone quality in the context of
      low but not high turnover renal osteodystrophy. Sclerostin also appears in the
      circulation suggesting additional roles outside the skeleton in normal and
      disease states. In patients with chronic kidney disease (CKD), serum levels are
      elevated several fold relative to healthy individuals. Emerging data suggest that
      these changes are associated with increased fracture rates but the relationship
      between sclerostin and cardiovascular disease is unclear. Additional
      epidemiologic studies that examine stage specific and patient sub-populations are
      needed to assess whether sclerostin elevations influence comorbidities associated
      with CKD.

PMID- 26288184
TI  - Cardiac resynchronization therapy: Identifying an activation delay by regional
      strain analysis.

PMID- 26288179
TI  - Neurogenin 3 Expressing Cells in the Human Exocrine Pancreas Have the Capacity
      for Endocrine Cell Fate.
AB  - Neurogenin 3 (NGN3) is necessary and sufficient for endocrine differentiation
      during pancreatic development and is expressed by a population of progenitor
      cells that give rise exclusively to hormone-secreting cells within islets. NGN3
      protein can be detected in the adult rodent pancreas only following certain types
      of injury, when it is transiently expressed by exocrine cells undergoing
      reprogramming to an endocrine cell fate. Here, NGN3 protein can be detected in 2%
      of acinar and duct cells in living biopsies of histologically normal adult human
      pancreata and 10% in cadaveric biopsies of organ donor pancreata. The percentage
      and total number of NGN3+ cells increase during culture without evidence of
      proliferation or selective cell death. Isolation of highly purified and viable
      NGN3+ cell populations can be achieved based on coexpression of the cell surface
      glycoprotein CD133. Transcriptome and targeted expression analyses of isolated
      CD133+ / NGN3+ cells indicate that they are distinct from surrounding exocrine
      tissue with respect to expression phenotype and Notch signaling activity, but
      retain high level mRNA expression of genes indicative of acinar and duct cell
      function. NGN3+ cells have an mRNA expression profile that resembles that of
      mouse early endocrine progenitor cells. During in vitro differentiation, NGN3+
      cells express genes in a pattern characteristic of endocrine development and
      result in cells that resemble beta cells on the basis of coexpression of insulin
      C-peptide, chromogranin A and pancreatic and duodenal homeobox 1. NGN3 expression
      in the adult human exocrine pancreas marks a dedifferentiating cell population
      with the capacity to take on an endocrine cell fate. These cells represent a
      potential source for the treatment of diabetes either through ex vivo
      manipulation, or in vivo by targeting mechanisms controlling their population
      size and endocrine cell fate commitment. 

PMID- 26288185
TI  - Large Nosocomial Outbreak Associated with a Norwegian Scabies Index Case
      Undergoing TNF-alpha Inhibitor Treatment: Management and Control.
AB  - We describe a large outbreak associated with a crusted (Norwegian) scabies case
      in an immunocompromised patient following treatment with TNF-alpha inhibitor
      (adalimumab) for psoriasis arthritis. The increasing use of TNF-alpha inhibitors
      should induce clinicians to consider this serious parasitic infection when
      evaluating skin rashes in patients receiving biologic therapies.

PMID- 26288183
TI  - Inhibition of Autophagy Potentiated the Antitumor Effect of Nedaplatin in
      Cisplatin-Resistant Nasopharyngeal Carcinoma Cells.
AB  - Nedaplatin, a cisplatin analog, was developed to reduce the toxicity of
      cisplatin, whereas it can be cross-resistant with cisplatin in some
      circumstances. This study aimed to investigate the role of autophagy in
      nedaplatin induced cell death in cisplatin-resistant nasopharyngeal carcinoma
      cells. Here, we showed that HNE1/DDP and CNE2/DDP cells were resistant to
      nedaplatin-induced cell death with reduced apoptotic activity. Nedaplatin
      treatment resulted in autophagosome accumulation and increased expression of LC3
      II, indicating the induction of autophagy by nedaplatin in HNE1/DDP and CNE2/DDP
      cells. Inhibition of autophagy by Bafilomycin A1 (Baf A1) and 3-Methyladenine (3
      MA) remarkably enhanced the antitumor efficacy of nedaplatin in HNE1/DDP and
      CNE2/DDP cells, suggesting that the resistance to nedaplatin-induced cell death
      was caused by enhanced autophagy in nedaplatin-resistant NPC cells. Additionally,
      Baf A1 enhanced reactive oxygen species (ROS) generation and apoptosis induced by
      nedaplatin in HNE1/DDP cells. Mechanistically, nedaplatin treatment caused
      activation of ERK1/2 and suppression of Akt/mTOR signaling pathways. While
      inhibition of ERK1/2 by MEK1/2 inhibitor, U0126, could reduce the expression of
      LC3-II in nedaplatin-resistant NPC cells. Furthermore, suppression of ROS could
      inhibit nedaplatin-induced ERK activation in HNE1/DDP cells, indicating that ROS
      and ERK were involved in nedaplatin-induced autophagy. Together, these findings
      suggested that autophagy played a cytoprotective role in nedaplatin-induced
      cytotoxicity of HNE1/DDP and CNE2/DDP cells. Furthermore, our results highlighted
      a potential approach to restore the sensitivity of cisplatin-resistant
      nasopharyngeal cancer cells to nedaplatin in combination with autophagy
      inhibitors. 

PMID- 26288186
TI  - Image Quality of 3rd Generation Spiral Cranial Dual-Source CT in Combination with
      an Advanced Model Iterative Reconstruction Technique: A Prospective Intra
      Individual Comparison Study to Standard Sequential Cranial CT Using Identical
      Radiation Dose.
AB  - OBJECTIVES: To prospectively intra-individually compare image quality of a 3rd
      generation Dual-Source-CT (DSCT) spiral cranial CT (cCT) to a sequential 4-slice
      Multi-Slice-CT (MSCT) while maintaining identical intra-individual radiation dose
      levels. METHODS: 35 patients, who had a non-contrast enhanced sequential cCT
      examination on a 4-slice MDCT within the past 12 months, underwent a spiral cCT
      scan on a 3rd generation DSCT. CTDIvol identical to initial 4-slice MDCT was
      applied. Data was reconstructed using filtered backward projection (FBP) and 3rd
      generation iterative reconstruction (IR) algorithm at 5 different IR strength
      levels. Two neuroradiologists independently evaluated subjective image quality
      using a 4-point Likert-scale and objective image quality was assessed in white
      matter and nucleus caudatus with signal-to-noise ratios (SNR) being subsequently
      calculated. RESULTS: Subjective image quality of all spiral cCT datasets was
      rated significantly higher compared to the 4-slice MDCT sequential acquisitions
      (p<0.05). Mean SNR was significantly higher in all spiral compared to sequential
      cCT datasets with mean SNR improvement of 61.65% (p*Bonferroni0.05<0.0024).
      Subjective image quality improved with increasing IR levels. CONCLUSION:
      Combination of 3rd-generation DSCT spiral cCT with an advanced model IR technique
      significantly improves subjective and objective image quality compared to a
      standard sequential cCT acquisition acquired at identical dose levels.

PMID- 26288188
TI  - Origin and Diversification of Meprin Proteases.
AB  - Meprins are astacin metalloproteases with a characteristic, easily recognizable
      structure, given that they are the only proteases with both MAM and MATH domains
      plus a transmembrane region. So far assumed to be vertebrate-specific, it is
      shown here, using a combination of evolutionary and genomic analyses, that
      meprins originated before the urochordates/vertebrates split. In particular,
      three genes encoding structurally typical meprin proteins are arranged in tandem
      in the genome of the urochordate Ciona intestinalis. Phylogenetic analyses showed
      that the protease and MATH domains present in the meprin-like proteins encoded by
      the Ciona genes are very similar in sequence to the domains found in vertebrate
      meprins, which supports them having a common origin. While many vertebrates have
      the two canonical meprin-encoding genes orthologous to human MEP1A and MEP1B
      (which respectively encode for the proteins known as meprin alpha and meprin
      beta), a single gene has been found so far in the genome of the chondrichthyan
      fish Callorhinchus milii, and additional meprin-encoding genes are present in
      some species. Particularly, a group of bony fish species have genes encoding
      highly divergent meprins, here named meprin-F. Genes encoding meprin-F proteins,
      derived from MEP1B genes, are abundant in some species, as the Amazon molly,
      Poecilia formosa, which has 7 of them. Finally, it is confirmed that the MATH
      domains of meprins are very similar to the ones in TRAF ubiquitin ligases, which
      suggests that meprins originated when protease and TRAF E3-encoding sequences
      were combined. 

PMID- 26288187
TI  - Solid Organ Transplantation in Patients with Inflammatory Bowel Diseases (IBD):
      Analysis of Transplantation Outcome and IBD Activity in a Large Single Center
      Cohort.
AB  - BACKGROUND: Currently, limited data of the outcome of inflammatory bowel disease
      (IBD) in patients after solid organ transplantation (SOT) are available. We aimed
      to analyze effects of SOT on the IBD course in a large IBD patient cohort.
      METHODS: Clinical data from 1537 IBD patients were analyzed for patients who
      underwent SOT (n = 31) between July 2002 and May 2014. Sub-analyses included SOT
      outcome parameters, IBD activity before and after SOT, and efficacy of IBD
      treatment. RESULTS: 4.74% of patients with ulcerative colitis (UC) and 0.84% of
      patients with Crohn's disease (CD) underwent SOT (p = 2.69 x 10(-6), UC vs. CD).
      77.4% of patients with SOT underwent liver transplantation (LTx) with tacrolimus
      based immunosuppressive therapy after SOT. All LTx were due to primary sclerosing
      cholangitis (PSC) or PSC overlap syndromes. Six patients (19.4%) required renal
      transplantation and one patient (3.2%) heart transplantation. A survival rate of
      83.9% after a median follow-up period of 103 months was observed. Before SOT,
      65.0% of patients were in clinical remission and 5 patients received
      immunosuppressive therapy (16.1%). After SOT, 61.0% of patients were in remission
      (p = 1.00 vs. before SOT) and 29.0% required IBD-specific immunosuppressive or
      anti-TNF therapy (p = 0.54 vs. before SOT). 42.9% of patients with worsening of
      IBD after SOT were at higher risk of needing steroid therapy for increased IBD
      activity (p = 0.03; relative risk (RR): 10.29; 95% CI 1.26-84.06). Four patients
      (13.0%) needed anti-TNF therapy after SOT (response rate 75%). CONCLUSIONS: SOT
      was more common in UC patients due to the higher prevalence of PSC-related liver
      cirrhosis in UC. Despite mainly tacrolimus-based immunosuppressive regimens,
      outcome of SOT and IBD was excellent in this cohort. In this SOT cohort,
      concomitant immunosuppressive therapy due to IBD was well tolerated.

PMID- 26288189
TI  - Effect of Model Variables on in vitro Erosion.
AB  - The aim of this study was to investigate the effects of tooth type
      (molar/premolar), tooth surface (buccal/lingual), smear layer or no smear layer,
      storage of specimens in deionised water, mode and speed of agitation, and rinsing
      method between cycles on mean step height loss and Knoop microhardness (KHN)
      change. Polished human enamel specimens embedded in acrylic resin were prepared
      from sound permanent molar and premolar tooth surfaces. A 0.3% (pH 3.2) solution
      of citric acid was used to erode the specimens, in a cycling procedure,
      consisting of 10 min immersion followed by rinsing in deionised water for 30 s
      with a spray bottle, for 5 cycles. The specimens were analysed with a non-contact
      white light profilometer and KHN. Molar teeth (148.99+/-24.49 KHN) and buccal
      surfaces (155.62+/-30.35 KHN) produced significantly less microhardness change
      compared to premolar (186.40+/-20.74 KHN) and lingual surfaces (179.76+/-23.21
      KHN; p<0001). The effect of storage and rinsing showed little difference in mean
      step height loss (<1 um) and microhardness change. With no smear layer a
      significantly lower mean step height loss and microhardness change (p<0.001) was
      observed. Agitation was performed with Orbital, Gyro and See-Saw rockers at 30,
      40, 60, and 70 rpm. The mean step height loss was largest for See-Saw at 70 rpm
      (11.73+/-0.91 MUm) and lowest for Orbital at 30 rpm (2.76+/-1.12 MUm). A
      statistical difference was found between all types of agitation and speeds
      (p<0.001). In conclusion, this study has shown that the variables investigated
      here have a significant impact on the measurable outcome, highlighting the
      importance of accurate and detailed method sections.

PMID- 26288190
TI  - Recurrent Pyogenic Granulomas with Underlying Arteriovenous Malformation: An
      Exclusively Rare Entity.
AB  - We report a case of recurrent localized pyogenic granulomas with underlying
      arteriovenous malformation in an 11-year-old male child on upper back with onset
      in early infancy. 

PMID- 26288191
TI  - Environmental Influences on Preschoolers' Physical Activity Levels in Various
      Early-Learning Facilities.
AB  - PURPOSE: This study aimed to: (a) compare the physical activity (PA) levels
      (i.e., moderate-to-vigorous PA [MVPA] and total PA [TPA]) of preschoolers in 3
      different early-learning environments (center-based childcare, home-based
      childcare, and full-day kindergarten [FDK]); and (b) assess which characteristics
      (e.g., play equipment, policies, etc.) of these settings influenced preschoolers'
      PA. METHOD: Twenty-seven facilities (9 centers, 10 homes, and 8 FDK) participated
      in this study. Participants (aged 2.5-5 years; n = 297) were fitted with
      ActicalTM accelerometers for 5 consecutive days during childcare/school hours to
      assess their PA. The Environment and Policy Assessment and Observation (EPAO)
      tool was used to objectively examine the PA environment of all participating
      facilities. Finally, demographic questionnaires were administered to
      preschoolers' parents/guardians. RESULTS: Preschoolers in FDK accumulated
      significantly more MVPA (p < .05; 3.33 min/hr) than those in center- (1.58
      min/hr) and home-based (1.75 min/hr) childcare, and they accumulated
      significantly more TPA (p < .05; 20.31 min/hr) than those in center-based
      childcare (18.36 min/hr). For FDK, the Active Opportunities, Sedentary
      Opportunities, Sedentary Environment, and Fixed Play Environment subscales of the
      EPAO significantly impacted both MVPA and TPA. For center-based childcare, only
      the Sedentary Environment subscale was found to impact MVPA and TPA. No subscales
      influenced children's MVPA or TPA in home-based childcare. CONCLUSIONS: This
      research underscores the need to encourage/support preschoolers' active behaviors
      in early-learning settings, particularly for those in center- and home-based
      childcare. Furthermore, this article highlights environmental and staff
      characteristics on which future PA programming should focus.

PMID- 26288192
TI  - Glutathione S-transferase gene polymorphism: Relation to cardiac iron overload in
      Egyptian patients with Beta Thalassemia Major.
AB  - OBJECTIVES: Estimating the prevalence of glutathione S-transferase gene
      polymorphism (GSTM1) null genotype among patients with beta thalassemia major
      (beta-TM) in relation to myocardial status assessed by tissue Doppler and cardiac
      siderosis assessed by cardiac magnetic resonance imaging (MRI) T2*. METHODS:
      Hundred patients with beta-TM and 100 healthy controls were enrolled. Complete
      blood count (CBC), mean serum ferritin and GSTM1 genotyping, echocardiography,
      tissue Doppler, and cardiac MRI T2* were done. RESULTS: Serum ferritin ranged
      from 1200 to 8000 ng/ml, and mean T2* value was 27.10 +/- 11.20 ms. Of patients,
      68 (68%) had no cardiac siderosis, while 24 (24%) with mild to moderate, and 8
      (8%) with sever cardiac siderosis. T2* values were not correlated with serum
      ferritin (r = -0.09, P = 0.50). GSTM1 null genotype was prevalent in 46% of
      patients and 40% of controls (P = 0.69). Patients with null genotype had
      significantly shorter T2* (P = 0.001), higher left ventricular end-diastolic
      diameter (P = 0.002), and shorter ejection time (P = 0.005) with no significant
      relation to serum ferritin (P = 0.122). GSTM1 null genotype was the only
      predictor for cardiac iron overload (P = 0.002). DISCUSSION: Serum ferritin
      concentrations have been shown to correlate poorly with all stages of cardiac
      dysfunction. Low cardiac MRI T2* values occur in patients with beta-TM despite
      good chelation therapy, suggesting a possible role of genetic factors in cardiac
      siderosis. CONCLUSION: GSTM1 null genotype is significantly associated with
      cardiac iron overload independent of serum ferritin in Egyptian patients with
      beta-TM.

PMID- 26288193
TI  - Sex, Myocardial Infarction, and the Failure of Risk Scores in Women.

PMID- 26288194
TI  - Mental Representations of Weekdays.
AB  - Keeping social appointments involves keeping track of what day it is. In
      practice, mismatches between apparent day and actual day are common. For example,
      a person might think the current day is Wednesday when in fact it is Thursday.
      Here we show that such mismatches are highly systematic, and can be traced to
      specific properties of their mental representations. In Study 1, mismatches
      between apparent day and actual day occurred more frequently on midweek days
      (Tuesday, Wednesday, and Thursday) than on other days, and were mainly due to
      intrusions from immediately neighboring days. In Study 2, reaction times to
      report the current day were fastest on Monday and Friday, and slowest midweek. In
      Study 3, participants generated fewer semantic associations for "Tuesday",
      "Wednesday" and "Thursday" than for other weekday names. Similarly, Google
      searches found fewer occurrences of midweek days in webpages and books. Analysis
      of affective norms revealed that participants' associations were strongly
      negative for Monday, strongly positive for Friday, and graded over the
      intervening days. Midweek days are confusable because their mental
      representations are sparse and similar. Mondays and Fridays are less confusable
      because their mental representations are rich and distinctive, forming two
      extremes along a continuum of change. 

PMID- 26288196
TI  - Increased insulin-like growth factor-1 in relation to cardiovascular function in
      polycystic ovary syndrome: friend or foe?
AB  - The incidence of cardiovascular disease (CVD) in patients with polycystic ovary
      syndrome (PCOS) is very high and conventional risk factors only partially explain
      excessive risk of developing CVD in patients of PCOS. The pathophysiology of PCOS
      is very unique, and several hormonal and metabolic changes occur. Several
      observations suggest that serum IGF-1 levels decrease in insulin resistance,
      which results in IGF-1 deficiency. In patient of PCOS, close relationships have
      been demonstrated between insulin resistance and serum IGF-1 levels.
      Hyperinsulinemic insulin resistance results in a general augmentation of
      steroidogenesis and LH release in PCOS. The action of IGF-1 varies in different
      tissues possibly via autocrine or paracrine mechanisms. The increase or decrease
      in IGF-1 in different tissues results in differential outcomes. Several studies
      suggest that lowered circulating IGF-1 levels play important role in the
      initiation of the cardiac hypertrophic response which results in the risk of
      cardiovascular disease. While recent results suggests that individual with
      elevated IGF-1 is protected against cardiovascular disease. Thus IGF-1 shows
      versatile pleiotropic actions. This review provides a current perspective on
      increased level of IGF-1 in PCOS and also adds to the current controversy
      regarding the roles of IGF-1 in cardiovascular disease. 

PMID- 26288195
TI  - Leukocyte Populations in Human Preterm and Term Breast Milk Identified by
      Multicolour Flow Cytometry.
AB  - BACKGROUND: Extremely preterm infants are highly susceptible to bacterial
      infections but breast milk provides some protection. It is unknown if leukocyte
      numbers and subsets in milk differ between term and preterm breast milk. This
      study serially characterised leukocyte populations in breast milk of mothers of
      preterm and term infants using multicolour flow cytometry methods for extended
      differential leukocyte counts in blood. METHODS: Sixty mothers of extremely
      preterm (<28 weeks gestational age), very preterm (28-31 wk), and moderately
      preterm (32-36 wk), as well as term (37-41 wk) infants were recruited. Colostrum
      (d2-5), transitional (d8-12) and mature milk (d26-30) samples were collected,
      cells isolated, and leukocyte subsets analysed using flow cytometry. RESULTS: The
      major CD45+ leukocyte populations circulating in blood were also detectable in
      breast milk but at different frequencies. Progression of lactation was associated
      with decreasing CD45+ leukocyte concentration, as well as increases in the
      relative frequencies of neutrophils and immature granulocytes, and decreases in
      the relative frequencies of eosinophils, myeloid and B cell precursors, and CD16-
      monocytes. No differences were observed between preterm and term breast milk in
      leukocyte concentration, though minor differences between preterm groups in some
      leukocyte frequencies were observed. CONCLUSIONS: Flow cytometry is a useful tool
      to identify and quantify leukocyte subsets in breast milk. The stage of lactation
      is associated with major changes in milk leukocyte composition in this
      population. Fresh preterm breast milk is not deficient in leukocytes, but shorter
      gestation may be associated with minor differences in leukocyte subset
      frequencies in preterm compared to term breast milk.

PMID- 26288197
TI  - Core-shell nanoparticles: synthesis and applications in catalysis and
      electrocatalysis.
AB  - Core-shell nanoparticles (CSNs) are a class of nanostructured materials that have
      recently received increased attention owing to their interesting properties and
      broad range of applications in catalysis, biology, materials chemistry and
      sensors. By rationally tuning the cores as well as the shells of such materials,
      a range of core-shell nanoparticles can be produced with tailorable properties
      that can play important roles in various catalytic processes and offer
      sustainable solutions to current energy problems. Various synthetic methods for
      preparing different classes of CSNs, including the Stober method, solvothermal
      method, one-pot synthetic method involving surfactants, etc., are briefly
      mentioned here. The roles of various classes of CSNs are exemplified for both
      catalytic and electrocatalytic applications, including oxidation, reduction,
      coupling reactions, etc. 

PMID- 26288198
TI  - Improving Rehabilitative Efforts for Juvenile Offenders Through the Use of
      Telemental Healthcare.
AB  - The use of videoconferencing technology in the provision of mental health
      services is expected to increase rapidly over the next several years. Given the
      high rates of juvenile offenders in need of such services and the new norms of
      communication among young people in general, technology-based service modalities
      are a promising approach for increasing the availability and intensity of
      services, as well as engagement and compliance with treatment recommendations.
      This article will discuss the current state of the juvenile justice system, the
      literature on the use of telemental healthcare (TMH) with delinquent youth, how
      TMH fits within the generally accepted model of correctional rehabilitation, and
      special considerations for applying TMH to this population and setting. Although
      there is no evidence to suggest negative outcomes associated with TMH, future
      research is greatly needed to justify its use. 

PMID- 26288200
TI  - Correction: The Opponent Channel Population Code of Sound Location Is an
      Efficient Representation of Natural Binaural Sounds.

PMID- 26288199
TI  - Salmeterol/fluticasone through breath-actuated inhaler versus pMDI: a randomized,
      double-blind, 12 weeks study.
AB  - OBJECTIVE: Salmeterol/fluticasone combination (SFC) formulated in a breath
      actuated inhaler (BAI) overcomes the co-ordination problem associated with the
      pressurized-metered dose inhaler (pMDIs). Our aim was to compare the efficacy and
      the safety of SFC given through the BAI versus the conventional pMDI in moderate
      to-severe asthmatics. METHODS: In this randomized, double-blind, double-dummy,
      prospective, active-controlled, parallel group, multicenter, 12 weeks study, 150
      asthmatics were randomized to receive SFC (25/125 mcg) through either BAI or
      pMDI. The primary efficacy endpoint was mean change in pre-dose morning PEFR
      value at 12 weeks and the secondary efficacy endpoints included, mean change in
      FEV(1), pre-bronchodilator FVC, pre-dose morning and evening PEFR, symptom scores
      at 2, 4, 8, and 12 weeks. Patient preferences for device and safety were also
      assessed. RESULTS: At 12 weeks, the mean change in pre-dose morning PEFR in BAI
      and pMDI groups was 50.72 L/min and 48.82 L/min, respectively (p < 0.0001; both
      groups) and the difference between the two groups was not significant. Both the
      treatment groups showed a statistically significant improvement in secondary
      endpoints at all-time points compared with baseline. The usability questionnaire
      assessment results showed that the BAI device was preferred by 75% of patients as
      compared with 25% preferring pMDI. SFC in both BAI and pMDI devices was found to
      be safe and well tolerated. CONCLUSION: This is the first study to demonstrate
      that SFC given through the BAI produces comparable efficacy and safety endpoints
      as pMDI. Additionally, BAI was the preferred inhaler by patients compared to
      conventional pMDI.

PMID- 26288201
TI  - [The clinical manifestations and neurophysiological features of long-lasting
      paroxysmal vertigo:theanalysis of the original observations].
AB  - The objective of the present study was to elucidate specific features of etiology
      and pathophysiology of recurring chronic vestibular dysfunction. It included 90
      patients with this pathology of whom 24 (26.6%) presented with vascular
      compression of the vestibulocochlear nerve diagnosed by means of high-field MRI.
      This method revealed the high frequency of positionally-dependent vestibular
      dysfunction associated with neurovascular interactions. Analysis of the state of
      vestibular dysfunction during the attack-free periods demonstrated the signs of
      latent vestibular dysfunction in 20 (83.3%) patients. The results of the study
      provide additional information on the prevalence of vascular compression of the
      vestibulocochlear nerve in the patients presenting with recurrent chronic
      dizziness; moreover, they make it possible to evaluate the state of vestibular
      function and develop the new diagnostic criteria for vestibular paroxismia. 

PMID- 26288202
TI  - [The new technologies for the intraoperative registration of the electrically
      evoked compound action potentials of the acoustical nerve by means of the neural
      response telemetry method].
AB  - The present article reports the results of a clinical study of the new wireless
      device CR120 designed for the intraoperative registration of electrode resistance
      and the electrically evoked compound action potential (EAP) of the acoustical
      nerve by means of neural response telemetry. The study has demonstrated the high
      effectiveness of the application of the new wireless device in clinical practice.
      It was shown that the registration of electrically evoked compound action
      potential with the help of the CR120 Intraoperative Remote Assistant took 22%
      less time than by the conventional method (p<0.001). Moreover, the trial revealed
      the strong correlation between the threshold EAP values recorded with the use of
      the new device and by the classical method. 

PMID- 26288203
TI  - [Hearing disorders in the children presenting with various chronic diseases].
AB  - The objective of the present study was to improve the effectiveness of early
      diagnostics and prophylaxis of hearing disturbances in the children presenting
      with various chronic diseases. As is known, there are several dozens of
      neurologic disorders associated with hearing disorders. By way of example, there
      is a group of nephropathologies responsible for the loss of hearing in the
      children. Specifically, hearing impairment can be one of the symptoms of diabetes
      mellitus. The patients presenting with mucopolysaccharidosis make up a group at
      risk of hearing impairment. Sensorineural loss of hearing is widespread among the
      children presenting with coeliac disease. The protocols for the treatment of
      certain pathologies envisage the application of certain medications possessed of
      the cytotoxic activity, such as preparations for chemo- and radiotherapy or
      cytostatic agents that suppress cell proliferation when applied for the
      management of some autoimmune diseases. It is concluded that cooperation between
      health providers representing different medical disciplines may be instrumental
      in the organization of efficacious screening for the detection of children with
      severe chronic pathology. 

PMID- 26288204
TI  - [Alterations in the status of a child with a cochlear implant in the course of
      rehabilitation].
AB  - The objective of the present publication was to demonstrate changes in the socio
      psychological status of the children with cochlear implants in the course of
      postoperative psycho-pedagogical rehabilitation. Another objective was to draw
      attention to the necessity of the acquisition of the new professional skills by
      the teachers of the deaf and hard of hearing subjects, speech and language
      pathologists. Special attention is given to the substantiation of dynamic psycho
      pedagogical classification of the children with a cochlear implant that should
      reflect the process of professional reorientation of the aforementioned
      specialists in the course of rehabilitation of their patients. 

PMID- 26288205
TI  - [Organization of pedagogical rehabilitation for the children with a cochlear
      implant].
AB  - The objective of the present study was to characterize the peculiarities
      oforganization of pedagogical rehabilitation for the children with a cochlear
      implant and to demonstrate the most effective forms of their upbringing and
      education. Special attention is given to the organization ofsuch work during the
      preschool period with reference to potential difficulties encountered in the
      education of the children suffering a delay in the speech development. 

PMID- 26288206
TI  - [The clinical manifestations and diagnostics of otitis media caused by
      tuberculosis].
AB  - The objective of the present study was to clarify the characteristic
      pathognomonic features of middle ear lesions associated with tuberculosis and the
      approaches to their diagnostics under the present-day conditions. The study
      included 11 cases (18 ears) of tuberculosis otitis media and the related lesions
      of the mastoid process diagnosed with the use of clinical, roentgenological,
      cytological, bacteriological, pathomorphological, and molecular-genetic methods
      (including PCR diagnostics). The primary localization of tuberculosis in the
      middle ear was documented in 6 patients; in 5 patients, it was associated with
      pulmonary involvement. Five patients presented with smoldering exudative otitis
      media and the remaining six ones with suppurative perforating otitis media. The
      tuberculous process was diagnosed with the use of various methods including
      clinical examination, bacteriological (9%), cytological (27.3%),
      pathomorphological (18%) studies, and PCR diagnostics (55%). Diagnosis was made
      within a period from 1 month to 1.5 years after the application of the patients
      for medical assistance which suggests the difficulty of verification of
      tuberculous etiology of the disease of the middle ear. It is concluded that the
      high index of suspicion in the case of smoldering middle ear pathology
      facilitates its early diagnostics and successful treatment. 

PMID- 26288207
TI  - [pH values in the pharynx of the patients presenting with compromised nasal
      breathing of inflammatory and non-inflammatory genesis concomitant with
      gastroesophageal reflux disease].
AB  - The objective of the present study was to estimate the influence of
      gastroesophageal reflux disease (GERD) on the pH values in the pharynx and nose.
      It included 87 patients at the age varying from 18 to 81 years admitted to the
      Irkutsk-based Railway Clinical Hospital and allocated to four groups. Group 1 was
      comprised of 25 patients presenting with gastroesophageal reflux disease and
      chronic rhinosinusitis (CRS), group 2 consisted of 29 patients with CRS in the
      absence of GERD, group 3 included 22 patients with nasal septum deformations
      (NSD) and GERD, group 4 included 11 patients with NSD and motor rhinitis without
      GERD. The control group was formed from 10 volunteers. pH was measured by the
      contact method with the use ofEkokhim indicator paper. Gastroesophageal reflux
      disease was diagnosed following the recommendations of the Montreal consensus. It
      was shown that pH values in the pharynx of the patients with compromised nasal
      breathing of any origin in combination with GERD were lower than in the absence
      of GERD and in the healthy volunteers. The study groups did not differ in terms
      of pH values in the nasal cavity. It is concluded that pH values 4 or lower may
      serve as the criterion for pharyngo-laryngeal reflux (PLR) concomitant with HERD
      while pH 5 occurs more frequently in the patients with compromised nasal
      breathing of any etiology, regardless of the presence or absence of
      GERD.Disordered nasal breathing of any genesis in the patients presenting with
      gastroesophageal reflux disease was associated with the feeling of the lump in
      the throat, congestion of the respiratory tract and the nose, pain in the ears,
      cardialgia, and irregular heartbeat. It isrecommended to use pH measurements as a
      criterion for diagnostics of pharyngo-laryngeal reflux in the patients presenting
      with gastroesophageal reflux disease. 

PMID- 26288209
TI  - [The experience with the application of a lyophilized xenodermograft for the
      treatment of the patients suffering from frequently recurring inflammation of the
      maxillary sinus in combination with alveolar fistula].
AB  - The objective of the present study was to summarize the data of the special
      literature concerning methods of the surgical treatment of odontogenic maxillary
      sinusitis complicated by the alveolar fistula with the purpose of using them for
      the improvement of the effectiveness of the treatment of the patients presenting
      with this pathology. The study group was comprised of 39 patients with
      odontogenic diseases of paranasal sinuses and alveolar fistulas. The alveolar
      fistulas were closed in 20 patients by means of plastic surgery with the use of a
      lyophilized xenodermograft prepared from the pig's skin. Not a single case of
      relapse of the inflammatory process in the maxillary sinuseswas documented within
      one year after the treatment by means of the closure of the alveolar fistula
      using the lyophilizedxenodermografts. 

PMID- 26288208
TI  - [The original method for bypass surgery of the tympanic cavity to treat chronic
      dysfunction of the Eustachian tube].
AB  - The objective of the present study was to improve the effectiveness of the
      treatment of intractable dysfunctionof the Eustachian tube responsible for the
      relapses of catarrhal and exudative otitis media. The authors developed the
      diaphragmatic slot valve integrated into the silicone tympanic shunt tube. The
      proposed diaphragmatic slot valve was shown to counterbalance extra- and
      intratympanic pressure at the experimentally found compression threshold equaling
      123.06 daPa. This original functional shunt ensured the continuous functioning of
      tensor tympani muscle and maintained tympano-tubal innervation. The comprehensive
      examination and treatment encompassed 104 patients (104 ears) presenting with
      long-standing dysfunction of the Eustachian tube. In 52 patients (52 ears),
      otitis media was treated with the use of the functional shunt tube and in the
      remaining 52 (52 ears) with the standard silicone shunt tube. The comparative
      analysis has demonstrated that the effectiveness of the treatment of intractable
      dysfunctionof the Eustachian tube can be increased by 13.3% using the functional
      tympanic shunt. Simultaneously, this method made it possible to totally normalize
      the ventilation function of the Eustachian tube in 51 (98.1%) patients. The
      duration of the treatment with the use of the functional shunt tube averaged
      42.11+/-8.46 days (in the patients with catarrhal inflammation of the middle ear)
      and 59.03+/-7.17 days (in the case of exudative otitis media) which was 42.9% and
      37.3% shorter respectively than the duration of the traditional treatment
      (p<0.5). 

PMID- 26288210
TI  - [Topical preparations for therapy of tonsillar pathology].
AB  - This paper highlights clinical and diagnostic aspects of tonsillar pathology with
      special reference to modern methods for the treatment of pharyngeal diseases of
      different etiology. A detailed characteristic of local symptomatic therapy is
      presented including the use of NSAIDs (non-steroidal anti-inflammatory drugs).
      These agents have advantages over other medications for local therapy due to high
      anti-inflammatory and analgesic activities. Also, they significantly improve the
      patients' quality of life. The use of a local anti-inflammatory drug is a major
      component of the treatment of inflammatory pharyngeal pathology. Regardless of
      the nature of the disease, either bacterial or viral. 

PMID- 26288211
TI  - [The complete elimination of the episodes of benign positional paroxysmal vertigo
      in a patient with the involvement of the posterior semicircular canal following
      the eccentric rotation test].
AB  - The objective of the present study was the clinical and neurophysiological
      analysis of the observations of a 42 year-old female patient suffering from
      benign paroxysmalpositional dizziness (BPPD) associated with the lesion of the
      posterior semicircular canal. The dynamic evaluation of the utricular function
      was performed during eccentric rotation of the patient in the vestibulometric
      chair at a speed of 300 degrees. The chair together with the patients was
      atomatically displaced during the rotation 3.5--4.0 cm to the right or left off
      the vertical axis, and the error in subjective perception of the deviation from
      the vertical was estimated. The saccular function was evaluated by recording
      cervical vestibular evoked myogenic potentials. The symptoms of BPPD were found
      to completely disappear after the eccentric rotation. Not a single spell of
      benign paroxysmalpositional dizziness was documented within 6 months after the
      eccentric rotation. The mechanisms underlying the elimination of these symptoms
      as a result of eccentric rotation are discussed.

PMID- 26288212
TI  - [Combined dizziness: a difficult case of diagnostics].
AB  - The present article is focused on the detailed analysis of the history of a
      patient suffering from combined dizziness including the entire course of the
      disease, the complicating complex of complaints, and the increasing number of
      abnormal components of the patient's condition. The specific features of various
      nosological forms of the disease are described as arising from different clinical
      entities causing vertigo. The special emphasis is laid on the diagnostic
      algorithm for the elucidation of these disorders. 

PMID- 26288213
TI  - [The surgical treatment of cholesteatoma of the pyramid of the temporal bone].
AB  - This paper presents in brief the data on epidemiology, classification,
      diagnostics, and current tendencies in the surgical treatment of cholesteatoma of
      the pyramid of the temporal bone. A clinical case of diagnostics and the surgical
      treatment ofpetrous apex cholesteatomainthe temporal bone is described. 

PMID- 26288214
TI  - [Diagnostics of Citelli's abscess by means of ultrasound scanning].

PMID- 26288215
TI  - [About rare causes of the loss of hearing].
AB  - The present paper reports a clinical case of local syphilitic meningoencephalitis
      known as Argyll-Robertson syndrome and manifested in the form of acute
      sensorineural loss of hearing. The patient was a 46 year old resident of the city
      of Irkutsk. He experienced the sharp impairment of hearing involving both ears
      with the accompanying feeling of dizziness, disturbed orientation of the
      locomotorbehaviour, the lurching gate, subfebrility, the loss of the ability to
      speak and write. The diagnosis was based on the presence of anisocoria, the
      absence of consensual pupillary reaction to the light, weak atropine action on
      the pupils, well expressed positive results of the VRDL (blood) and RW (liquor)
      tests, an enhanced signal from the left temporal region in the T-2 regime during
      MRI, positive hearing dynamics within 12 hours after the onset of anti
      inflammatory, antibacterial and infusion therapy. The specific feature of the
      clinical case being considered is differential diagnostics was performed with the
      purpose of distinguishing it from otogenic brain abscess associated with chronic
      left-hand mesotympanitis. 

PMID- 26288218
TI  - Fast and Efficient Preparation of Exfoliated 2H MoS2 Nanosheets by Sonication
      Assisted Lithium Intercalation and Infrared Laser-Induced 1T to 2H Phase
      Reversion.
AB  - Exfoliated 2H molybdenum disulfide (MoS2) has unique properties and potential
      applications in a wide range of fields, but corresponding studies have been
      hampered by the lack of effective routes to it in bulk quantities. This study
      presents a rapid and efficient route to obtain exfoliated 2H MoS2, which combines
      fast sonication-assisted lithium intercalation and infrared (IR) laser-induced
      phase reversion. We found that the complete lithium intercalation of MoS2 with
      butyllithium could be effected within 1.5 h with the aid of sonication. The 2H to
      1T phase transition that occurs during the lithium intercalation could be also
      reversed by IR laser irradiation with a DVD optical drive. 

PMID- 26288217
TI  - Ruthenium-Catalyzed meta-Selective C-H Bromination.
AB  - The first example of a transition-metal-catalyzed, meta-selective C-H bromination
      procedure is reported. In the presence of catalytic [{Ru(p-cymene)Cl2 }2 ],
      tetrabutylammonium tribromide can be used to functionalize the meta C-H bond of 2
      phenylpyridine derivatives, thus affording difficult to access products which are
      highly predisposed to further derivatization. We demonstrate this utility with
      one-pot bromination/arylation and bromination/alkenylation procedures to deliver
      meta-arylated and meta-alkenylated products, respectively, in a single step.

PMID- 26288216
TI  - Pharmaceutical Optimization of Peptide Toxins for Ion Channel Targets: Potent,
      Selective, and Long-Lived Antagonists of Kv1.3.
AB  - To realize the medicinal potential of peptide toxins, naturally occurring
      disulfide-rich peptides, as ion channel antagonists, more efficient
      pharmaceutical optimization technologies must be developed. Here, we show that
      the therapeutic properties of multiple cysteine toxin peptides can be rapidly and
      substantially improved by combining direct chemical strategies with high
      throughput electrophysiology. We applied whole-molecule, brute-force, structure
      activity analoging to ShK, a peptide toxin from the sea anemone Stichodactyla
      helianthus that inhibits the voltage-gated potassium ion channel Kv1.3, to
      effectively discover critical structural changes for 15* selectivity against the
      closely related neuronal ion channel Kv1.1. Subsequent site-specific polymer
      conjugation resulted in an exquisitely selective Kv1.3 antagonist (>1000* over
      Kv1.1) with picomolar functional activity in whole blood and a pharmacokinetic
      profile suitable for weekly administration in primates. The pharmacological
      potential of the optimized toxin peptide was demonstrated by potent and sustained
      inhibition of cytokine secretion from T cells, a therapeutic target for
      autoimmune diseases, in cynomolgus monkeys. 

PMID- 26288219
TI  - Searching the Hearts of Graphene-like Molecules for Simplicity, Sensitivity, and
      Logic.
AB  - If quantum interference patterns in the hearts of polycyclic aromatic
      hydrocarbons could be isolated and manipulated, then a significant step toward
      realizing the potential of single-molecule electronics would be achieved. Here we
      demonstrate experimentally and theoretically that a simple, parameter-free,
      analytic theory of interference patterns evaluated at the mid-point of the HOMO
      LUMO gap (referred to as M-functions) correctly predicts conductance ratios of
      molecules with pyrene, naphthalene, anthracene, anthanthrene, or azulene hearts.
      M-functions provide new design strategies for identifying molecules with phase
      coherent logic functions and enhancing the sensitivity of molecular-scale
      interferometers. 

PMID- 26288220
TI  - Interdomain Linker Determines Primarily the Structural Stability of Dystrophin
      and Utrophin Tandem Calponin-Homology Domains Rather than Their Actin-Binding
      Affinity.
AB  - Tandem calponin-homology (CH) domains are the most common actin-binding domains
      in proteins. However, structural principles underlying their function are poorly
      understood. These tandem domains exist in multiple conformations with varying
      degrees of inter-CH-domain interactions. Dystrophin and utrophin tandem CH
      domains share high sequence similarity (~82%), yet differ in their structural
      stability and actin-binding affinity. We examined whether the conformational
      differences between the two tandem CH domains can explain differences in their
      stability and actin binding. Dystrophin tandem CH domain is more stable by ~4
      kcal/mol than that of utrophin. Individual CH domains of dystrophin and utrophin
      have identical structures but differ in their relative orientation around the
      interdomain linker. We swapped the linkers between dystrophin and utrophin tandem
      CH domains. Dystrophin tandem CH domain with utrophin linker (DUL) has similar
      stability as that of utrophin tandem CH domain. Utrophin tandem CH domain with
      dystrophin linker (UDL) has similar stability as that of dystrophin tandem CH
      domain. Dystrophin tandem CH domain binds to F-actin ~30 times weaker than that
      of utrophin. After linker swapping, DUL has twice the binding affinity as that of
      dystrophin tandem CH domain. Similarly, UDL has half the binding affinity as that
      of utrophin tandem CH domain. However, changes in binding free energies due to
      linker swapping are much lower by an order of magnitude compared to the
      corresponding changes in unfolding free energies. These results indicate that the
      linker region determines primarily the structural stability of tandem CH domains
      rather than their actin-binding affinity. 

PMID- 26288221
TI  - Linking the evidence between urinary retention and antipsychotic or
      antidepressant drugs: A systematic review.
AB  - AIMS: Urinary retention (UR) occurs in patients on antipsychotic and
      antidepressant medication despite no apparent underlying urological cause. This
      review was undertaken to ascertain which of these medications are associated with
      UR and how often. METHODS: A systematic literature search for evidence on
      antipsychotic and antidepressant medications and UR was completed in June 2015
      using Scopus, Pubmed, Web of Science, and the Cochrane library. Search terms
      included urinary retention, antidepressants and antipsychotics as well as
      individual drug names. Filters used were: humans and English language. PRISMA
      guidelines were employed. RESULTS: Out of 614 articles initially identified, one
      meta-analysis, five RCT's, five cohort studies and 27 case reports were finally
      included. There was a wide range of definitions of UR. Studies which
      appropriately defined UR revealed it occurred in 1/21 patients on ziprasidone (an
      atypical antipsychotic), 17.6% of those on imipramine but only 0.1% of those on
      all tricyclic antidepressants analysed together. It was not reported in any of
      the 1,139 patients given duloxetine (a combined serotonin and noradrenaline
      reuptake inhibitor). It was reported in 0.025% of patients on selective serotonin
      reuptake inhibitors. UR was also reported in patients on typical antispychotics,
      selective noradrenaline reuptake inhibitors but the studies did not define UR.
      The majority of case reports reported an improvement in UR on discontinuation or
      dose reduction. CONCLUSION: Antipsychotics and antidepressants interact with the
      urinary system in many ways. Clinicians treating acute UR need to keep in mind
      the role of antipsychotic and antidepressants as a precipitating cause.
      Neurourol. Urodynam. 35:866-874, 2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 26288222
TI  - Medication Underuse in Aging Outpatients with Cardiovascular Disease: Prevalence,
      Determinants, and Outcomes in a Prospective Cohort Study.
AB  - BACKGROUND: Cardiovascular disease is a leading cause of death in older people,
      and the impact of being exposed or not exposed to preventive cardiovascular
      medicines is accordingly high. Underutilization of beneficial drugs is common,
      but prevalence estimates differ across settings, knowledge on predictors is
      limited, and clinical consequences are rarely investigated. METHODS: Using data
      from a prospective population-based cohort study, we assessed the prevalence,
      determinants, and outcomes of medication underuse based on cardiovascular
      criteria from Screening Tool To Alert to Right Treatment (START). RESULTS:
      Medication underuse was present in 69.1% of 1454 included participants (mean age
      71.1 +/- 6.1 years) and was significantly associated with frailty (odds ratio:
      2.11 [95% confidence interval: 1.24-3.63]), body mass index (1.03 [1.01-1.07] per
      kg/m2), and inversely with the number of prescribed drugs (0.84 [0.79-0.88] per
      drug). Using this information for adjustment in a follow-up evaluation (mean
      follow-up time 2.24 years) on cardiovascular and competing outcomes, we found no
      association of medication underuse with cardiovascular events (fatal and non
      fatal) (hazard ratio: 1.00 [0.65-1.56]), but observed a significant association
      of medication underuse with competing deaths from non-cardiovascular causes (2.52
      [1.01-6.30]). CONCLUSION: Medication underuse was associated with frailty and
      adverse non-cardiovascular clinical outcomes. This may suggest that
      cardiovascular drugs were withheld because of serious co-morbidity or that
      concurrent illness can preclude benefit from cardiovascular prevention. In the
      latter case, adapted prescribing criteria should be developed and evaluated in
      those patients.

PMID- 26288225
TI  - Ligand pi-radical interaction with f-shell unpaired electrons in phthalocyaninato
      lanthanoid single-molecule magnets: a solution NMR spectroscopic and DFT study.
AB  - The phthalocyaninato double-decker complexes [M(obPc)2 ](0) (M= Y(III) , Tb(III)
      , Dy(III) ; obPc=2,3,9,10,16,17,23,24-octabutoxyphthalocyaninato), along with
      their reduced ([M(obPc)2 ](-) [P(Ph)4 ](+) ; M=Tb(III) , Dy(III) ) and oxidized
      ([M(obPc)2 ](+) [SbCl6 ](-) (M=Y(III) , Tb(III) ) counterparts were studied with
      (1) H, (13) C and 2D NMR. From the NMR data of the neutral (i.e., with one
      unpaired electron in the ligands) and anionic Tb(III) complexes, along with the
      use of dispersion corrected DFT methods, it was possible to separate the metal
      centered and ligand-centered contributions to the hyperfine NMR shift. These
      contributions to the (1) H and (13) C hyperfine NMR shifts were further analyzed
      in terms of pseudocontact and Fermi contact shifts. Furthermore, from a
      combination of NMR data and DFT calculations, we have determined the spin
      multiplicity of the neutral complexes [M(obPc)2 ](0) (M=Tb(III) and Dy(III) ) at
      room temperature. From the NMR data of the cationic Tb(III) complex, for which
      actually no experimental structure determination is available, we have analyzed
      the structural changes induced by oxidation from its neutral/anionic species and
      shown that the interligand distance decreases upon oxidation. The fast electron
      exchange process between the neutral and anionic Tb(III) double-decker complexes
      was also studied. 

PMID- 26288224
TI  - Feral Cats Are Better Killers in Open Habitats, Revealed by Animal-Borne Video.
AB  - One of the key gaps in understanding the impacts of predation by small mammalian
      predators on prey is how habitat structure affects the hunting success of small
      predators, such as feral cats. These effects are poorly understood due to the
      difficulty of observing actual hunting behaviours. We attached collar-mounted
      video cameras to feral cats living in a tropical savanna environment in northern
      Australia, and measured variation in hunting success among different
      microhabitats (open areas, dense grass and complex rocks). From 89 hours of
      footage, we recorded 101 hunting events, of which 32 were successful. Of these
      kills, 28% were not eaten. Hunting success was highly dependent on microhabitat
      structure surrounding prey, increasing from 17% in habitats with dense grass or
      complex rocks to 70% in open areas. This research shows that habitat structure
      has a profound influence on the impacts of small predators on their prey. This
      has broad implications for management of vegetation and disturbance processes
      (like fire and grazing) in areas where feral cats threaten native fauna.
      Maintaining complex vegetation cover can reduce predation rates of small prey
      species from feral cat predation. 

PMID- 26288223
TI  - Gefitinib and Erlotinib Lead to Phosphorylation of Eukaryotic Initiation Factor 2
      Alpha Independent of Epidermal Growth Factor Receptor in A549 Cells.
AB  - Gefitinib and erlotinib are anticancer agents, which inhibit epidermal growth
      factor receptor (EGFR) tyrosine kinase. Interstitial lung disease (ILD) occurs in
      patients with non-small cell lung cancer receiving EGFR inhibitors. In the
      present study, we examined whether gefitinib- and erlotinib-induced lung injury
      related to ILD through endoplasmic reticulum (ER) stress, which is a causative
      intracellular mechanism in cytotoxicity caused by various chemicals in
      adenocarcinomic human alveolar basal epithelial cells. These two EGFR inhibitors
      increased Parkinson juvenile disease protein 2 and C/EBP homologous protein mRNA
      expressions, and activated the eukaryotic initiation factor (eIF)
      2alpha/activating transcription factor 4 pathway without protein kinase R-like ER
      kinase activation in A549 cells. Gefitinib and erlotinib caused neither ER stress
      nor cell death; however, these agents inhibited cell growth via the reduction of
      cyclin-D1 expression. Tauroursodeoxycholic acid, which is known to suppress
      eIF2alpha phosphorylation, cancelled the effects of EGFR inhibitors on cyclin-D1
      expression and cell proliferation in a concentration-dependent manner. The
      results of an EGFR-silencing study using siRNA showed that gefitinib and
      erlotinib affected eIF2alpha phosphorylation and cyclin-D1 expression independent
      of EGFR inhibition. Therefore, the inhibition of cell growth by these EGFR
      inhibitors might equate to impairment of the alveolar epithelial cell repair
      system via eIF2alpha phosphorylation and reduced cyclin-D1 expression. 

PMID- 26288226
TI  - Glycemic Stability Through Islet-After-Kidney Transplantation Using an
      Alemtuzumab-Based Induction Regimen and Long-Term Triple-Maintenance
      Immunosuppression.
AB  - Pancreatic islet transplantation is performed in a select group of patients with
      type 1 diabetes mellitus. Immunosuppressive regimens play an important role in
      long-term islet function. We aimed to investigate the efficacy of islet
      transplantation in patients with type 1 diabetes and a previous kidney
      transplantation using an alemtuzumab-based induction regimen and triple
      maintenance immunosuppression. Patients with type 1 diabetes, who had received a
      kidney transplant previously, were treated with alemtuzumab as induction therapy
      for their first islet transplantation and basiliximab induction therapy for
      subsequent islet transplantations. Maintenance immunosuppression consisted of
      triple immunosuppression (tacrolimus, mycophenolate mofetil, and prednisolone).
      Thirteen patients (age 50.9 +/- 9.2 years, duration of diabetes 35 +/- 9 years)
      received a total of 22 islet transplantations. One- and 2-year insulin
      independence was 62% and 42%, respectively; graft function was 100% and 92%,
      respectively. HbA1c dropped from 57.2 +/- 13.1 (7.4 +/- 1.2%) to 44.5 +/- 11.8
      mmol/molHb (6.2 +/- 0.9%) (p = 0.003) after 2 years. Six of 13 patients suffered
      from severe hypoglycemia before islet transplantation. After transplantation,
      severe hypoglycemia was restricted to the only patient who lost graft function.
      Creatinine clearance was unchanged. Islet-after-kidney transplantation in
      patients with type 1 diabetes using an alemtuzumab-based induction regimen leads
      to considerable islet allograft function and improvement in glycemic control. 

PMID- 26288228
TI  - Memory Effects on Movement Behavior in Animal Foraging.
AB  - An individual's choices are shaped by its experience, a fundamental property of
      behavior important to understanding complex processes. Learning and memory are
      observed across many taxa and can drive behaviors, including foraging behavior.
      To explore the conditions under which memory provides an advantage, we present a
      continuous-space, continuous-time model of animal movement that incorporates
      learning and memory. Using simulation models, we evaluate the benefit memory
      provides across several types of landscapes with variable-quality resources and
      compare the memory model within a nested hierarchy of simpler models (behavioral
      switching and random walk). We find that memory almost always leads to improved
      foraging success, but that this effect is most marked in landscapes containing
      sparse, contiguous patches of high-value resources that regenerate relatively
      fast and are located in an otherwise devoid landscape. In these cases, there is a
      large payoff for finding a resource patch, due to size, value, or locational
      difficulty. While memory-informed search is difficult to differentiate from other
      factors using solely movement data, our results suggest that disproportionate
      spatial use of higher value areas, higher consumption rates, and consumption
      variability all point to memory influencing the movement direction of animals in
      certain ecosystems. 

PMID- 26288227
TI  - Lower Circulating B12 Is Associated with Higher Obesity and Insulin Resistance
      during Pregnancy in a Non-Diabetic White British Population.
AB  - OBJECTIVE: Vitamin B12 and folate are critical micronutrients needed to support
      the increased metabolic demands of pregnancy. Recent studies from India have
      suggested that low vitamin B12 and folate concentrations in pregnancy are
      associated with increased obesity; however differences in diet, antenatal vitamin
      supplementation, and socioeconomic status may limit the generalisability of these
      findings. We aimed to explore the cross-sectional relationship of circulating
      serum vitamin B12 and folate at 28 weeks' gestation with maternal adiposity and
      related biochemical markers in a white non diabetic UK obstetric cohort. METHODS:
      Anthropometry and biochemistry data was available on 995 women recruited at 28
      weeks gestation to the Exeter Family Study of Childhood Health. Associations
      between B12 and folate with maternal BMI and other obesity-related biochemical
      factors (HOMA-R, fasting glucose, triglycerides, HDL and AST) were explored using
      regression analysis, adjusting for potential confounders (socioeconomic status,
      vegetarian diet, vitamin supplementation, parity, haemodilution (haematocrit)).
      RESULTS: Higher 28 week BMI was associated with lower circulating vitamin B12 (r
      = -0.25; P<0.001) and folate (r = -0.15; P<0.001). In multiple regression
      analysis higher 28 week BMI remained an independent predictor of lower
      circulating B12 (beta (95% CI) = -0.59 (-0.74, -0.44) i.e. for every 1% increase
      in BMI there was a 0.6% decrease in circulating B12). Other markers of
      adiposity/body fat metabolism (HOMA-R, triglycerides and AST) were also
      independently associated with circulating B12. In a similar multiple regression
      AST was the only independent obesity-related marker associated with serum folate
      (beta (95% CI) = 0.16 (0.21, 0.51)). CONCLUSION: In conclusion, our study has
      replicated the previous Indian findings of associations between lower serum B12
      and higher obesity and insulin resistance during pregnancy in a non-diabetic
      White British population. These findings may have important implications for
      fetal and maternal health in obese pregnancies.

PMID- 26288229
TI  - Prevalence of Oral and Maxillofacial Trauma in Elders Admitted to a Reference
      Hospital in Northeastern Brazil.
AB  - OBJECTIVE: To know the prevalence and etiology of oral and maxillofacial trauma
      in elders. METHODS: Analytical quantitative cross-sectional study conducted at a
      public trauma hospital located in Fortaleza-Ceara, Brazil. The study population
      comprised patients with trauma who were hospitalized from April to August 2014.
      Of these patients, patients with oral and maxillofacial trauma were chosen to be
      included in the research. A questionnaire was administered in order to obtain
      information on socio-demographics, systemic comorbidities, use of medication,
      deleterious habits (smoking and alcohol consumption), etiology of oral and
      maxillofacial trauma and type of pre-hospital care. RESULTS: Of the 280 elderly
      hospitalized with trauma, 47 had oral and maxillofacial trauma, with a prevalence
      of 16.8%. In this group, the age ranged from 60 to 88 years, with a mean age of
      72.4 years (SD+/- 8.38). The elderly were mostly women (55.3%), self-declared
      pardos (53.2%), who presented with cardiovascular disorders (48.9%), and who
      received formal pre-hospital care (70.2%). Elderly who were in the 60-69 years
      age group, spent 6-9 years at school and drank alcohol were 2.64, 3.75, and 1.97,
      respectively, more likely to suffer oral and maxillofacial trauma. The main
      causes of trauma were physical aggression, traffic accidents, falls and domestic
      accidents. All of the physical aggressions resulted in oral and maxillofacial
      traumas, and the elderly who suffered traffic accidents were four times more
      likely to have oral and maxillofacial trauma. CONCLUSION: The prevalence of 16.8%
      and the lack of research on oral and maxillofacial traumas in the elderly is
      worrisome and should be included in the oral health indicators for the elderly
      population to support the importance of oral health.

PMID- 26288230
TI  - Impact of Rivastigmine on Cognitive Dysfunction and Falling in Parkinson's
      Disease Patients.
AB  - BACKGROUND: The purpose of this study was to observe the incidence of falls in
      Parkinson's disease (PD) patients with different cognitive levels and to
      investigate the effect of the cholinesterase inhibitor Rivastigmine on cognitive
      dysfunction and falling in PD patients. SUBJECTS AND METHODS: Data from 176 PD
      patients participating in the collaborative PD study between June 2010 and June
      2014 were collected; the Chinese edition of the Montreal Cognitive Assessment
      (MoCA) score was used to evaluate the cognitive function of patients, and falls
      were recorded. PD patients with cognitive dysfunction were randomly administered
      either a placebo or Rivastigmine. The cognitive function changes and difference
      in fall incidence were compared between the 2 groups. RESULTS: The average number
      of falls per person in PD patients without cognitive impairment dysfunction was
      significantly lower than that in patients in the PD mild cognitive impairment (PD
      MCI) group and that in the PD dementia (PDD) group (p < 0.01, p < 0.001,
      respectively), and the incidence of falls was significantly lower than that in
      patients in the PD-MCI and PDD groups (p < 0.01, p < 0.01, respectively).
      Compared to the PD-MCI group, the incidence of falls of patients in the PDD group
      (OR 2.45, 95% CI 0.97-6.20, p < 0.01) and the number of falls per person were
      significantly increased (p < 0.01). After taking the placebo or Rivastigmine for
      12 months, the MoCA scores of patients in the Rivastigmine treatment group were
      significantly higher than those of the control group (p = 0.002). The number of
      falls per person and the incidence of falls of patients in Rivastigmine treatment
      group were significantly lower than those in the placebo group (p < 0.01).
      CONCLUSION: This study suggests that the degree of cognitive impairment is
      closely associated with the incidence of falls, and the cholinesterase inhibitor
      Rivastigmine can delay the deterioration of cognitive function and lower the
      incidence of falls in PD patients.

PMID- 26288232
TI  - Reduced Cognitive-Motor Interference on Voluntary Balance Control in Older Tai
      Chi Practitioners.
AB  - BACKGROUND AND PURPOSE: Recent dual-task studies suggest that Tai Chi
      practitioners displayed better control of standing posture and maintained a
      quicker response time of postural muscle activation during a stepping down
      activity. Whether this effect extends to voluntary balance control, specifically
      the limits of excursion of the center of pressure, remains to be examined. The
      purpose of this study was to evaluate the cognitive-motor interference pattern by
      examining the effects of a concurrently performed cognitive task on attention of
      voluntary balance control in older adults who are long-term practitioners of Tai
      Chi. METHODS: Ten older Tai Chi practitioners and 10 age-matched nonpractitioners
      performed a voluntary balance task that required them to shift their weight to
      reach a preset target in the forward and backward directions, with (single task,
      ST) and without (dual task, DT) a secondary cognitive task, which was the
      counting backward task. The counting backward task required the individual to
      compute and verbalize a series of arithmetic differences between a given pair of
      randomly generated numbers. The cognitive task was also performed independently
      (cognitive-ST). All trials were performed in a random order. Balance outcomes
      included reaction time, movement velocity, and maximal excursion of the center of
      pressure provided by the NeuroCom system. Cognitive outcome was the number of
      correct responses generated within the 8-second trial during the ST and DT
      conditions. Outcome variables were analyzed using a 2-factor, group by task,
      analysis of variance. DT costs for the variables were calculated as the relative
      difference between ST and DT conditions and were compared between the 2 groups
      using independent t tests. RESULTS: Tai Chi practitioners displayed shorter
      reaction times (P < .001) and faster movement velocities (P < .05) of their
      center of pressure than older nonpractitioners for both directions; however, no
      difference was found between the maximal excursions of the 2 groups. Cost
      analyses revealed that reaction time and cognitive costs were significantly lower
      in the Tai Chi practitioners for both forward and backward directions (P < .05);
      however, similar findings for movement velocity costs were significant only in
      the backward direction (P < .05). DISCUSSION AND CONCLUSIONS: Our results suggest
      that Tai Chi practitioners expended fewer motor and cognitive resources than
      older nonpractitioners during a fairly complex (dynamic) postural equilibrium
      task while performing a verbal working memory task. They exhibited lesser
      cognitive-motor interference and thus better allocation of attentional resources
      toward the voluntary balance control task. Given that dynamic balance is a
      crucial prerequisite for walking and dual-tasking ability is considered to be a
      significant predictor of falls in older adults, our results might point at the
      possible long-term benefits of Tai Chi practice to counteract age-related decline
      in dual-tasking ability. Findings present preliminary data for further
      investigation, especially related to potential benefits in fall prevention.

PMID- 26288233
TI  - A Preliminary Study of the Utilization of Maximal and Rapid Strength
      Characteristics to Identify Chair-Rise Performance Abilities in Very Old Adults.
AB  - BACKGROUND: Maximal and rapid strength characteristics of the knee extensor and
      flexor muscles play an important role in fall prevention and walking-related
      performances; however, few studies have investigated the ability of these
      variables to identify chair-rise performances in very old adults. PURPOSE: To
      examine the effectiveness of maximal and rapid isometric strength characteristics
      of the knee extensors and flexors to differentiate between very old adults who
      are able (higher functioning) versus unable (lower functioning) to independently
      rise from a chair. METHODS: Nine higher functioning (age, 87 +/- 6 years) and 6
      lower functioning (age, 89 +/- 6 years) very old adults performed 2 isometric
      maximal voluntary contractions of the knee extensors and flexors. Peak moment and
      absolute and relative rate of moment development (RMD) at the early (0-50 ms) and
      late (0-200 ms) phases of muscle contraction were examined during each maximal
      voluntary contraction. RESULTS: Absolute and relative RMD values at 0 to 50 ms
      were greater (P = .02 and .03, respectively) in the higher functioning than in
      the lower functioning individuals for both the knee extensors and flexors.
      However, no group-related differences (P = .39-.58) were observed in either
      muscle group for peak moment or absolute and relative RMD at 0 to 200 ms.
      CONCLUSIONS: Early rapid moment production of the knee extensors and flexors may
      be an effective measure for discriminating between very old adults of different
      chair-rise performance abilities. Physical therapists and other practitioners may
      use these findings to help with the identification and early detection of older
      adults who are at a high risk for functional decline.

PMID- 26288231
TI  - Preanalytic parameters in epidermal growth factor receptor mutation testing for
      non-small cell lung carcinoma: A review of cytologic series.
AB  - The results from molecular assays can be affected significantly by the
      preanalytic condition of cytologic samples. The authors review current knowledge
      on the use of cytologic samples for epidermal growth factor receptor (EGFR)
      mutation testing in non-small cell lung cancer with a focus on preanalytic
      parameters. A systematic electronic search of the MEDLINE database was performed
      to identify original articles that reported the use of cytologic samples for EGFR
      molecular analysis and included a minimum of 100 samples. The information
      collected included author(s), journal, and year of publication; number of
      patients and samples; sampling method; type of preparation; type of fixative;
      staining techniques; mutation analysis techniques; tumor cellularity; the
      percentage of tumor cells; data on DNA quantity, quality, and concentration;
      failed assays; and the mutation rate. EGFR mutation analysis was conducted on
      4999 cytologic samples from 22 studies that fulfilled the inclusion criteria.
      Fine-needle aspirates and pleural effusions were the most common types of
      specimens used. DNA was mainly extracted from cell blocks and smears, and the
      most commonly reported fixatives included formalin, ethanol, and CytoLyt.
      Cellularity assessments and DNA yields were available from 5 studies each. The
      average success rate for the assays that used cytologic specimens was 95.87%
      (range, 85.2%-100%). The mutation rate ranged from 6% to 50.46%, and a higher
      mutation detection rate and lower numbers of insufficient cases were reported for
      pleural effusions and lymph node samples from endobronchial ultrasound-guided
      transbronchial needle aspiration compared with histologic specimens. Low
      cellularity and a low percentage of tumor cells were associated with higher test
      failure rates. Future guidelines should consider the current data for specific
      recommendations regarding cytologic samples.

PMID- 26288234
TI  - Test-Retest Reliability and Validity of the Malay Version Life Habits Assessment
      (LIFE-H 3.1) to Measure Social Participation in Adults With Physical
      Disabilities.
AB  - BACKGROUND AND PURPOSE: Social participation restriction is a common barrier
      encountered by older adults and individuals with physical disabilities. To best
      direct the limited resource to support social services for individuals with
      disability, there is a need to objectively measure social participation
      restriction. A number of tools to measure levels of social participation are
      available, but none of them has been translated into the Malay language. This
      cross-sectional study examined the test-retest reliability and concurrent
      validity of the Life Habits Assessment (LIFE-H 3.1) that had been translated and
      culturally adapted to the Malay language. METHODS: Seventy-five individuals with
      physical disabilities (age, mean [standard deviation] = 58 [10] years; 49 males)
      participated in this study. Participants were interviewed twice with the Malay
      version LIFE-H 3.1, approximately 1 week apart. The Barthel Index (BI) and the
      World Health Organization Assessment of Quality of Life-Brief version (WHOQoL
      BREF) were administered in the first interview as well. Intraclass correlation
      coefficients and the Bland-Altman Bias D were used to examine test-retest
      reliability. The Spearman correlation coefficients were computed to quantify the
      correlation between the Malay version LIFE-H 3.1 and the BI and the WHOQoL-BREF,
      respectively, to examine the concurrent validity of the Malay version LIFE-H 3.1.
      Furthermore, standard error of measurement and minimal detectable change were
      calculated. RESULTS: The Malay version LIFE-H 3.1 had excellent test-retest
      reliability as evidenced by good to excellent intraclass correlation coefficients
      (0.71-0.95) and minimal Bland-Altman biases (0.01-0.12). The correlations between
      the Malay version LIFE-H 3.1 and the BI were fair to good (r = 0.28-0.69). The
      correlations between the Malay version LIFE-H 3.1 and the WHOQoL-BREF were weak
      to fair, ranging from 0.02 to 0.57. CONCLUSIONS: The Malay version LIFE-H 3.1
      demonstrates excellent test-retest reliability and satisfactory validity. This
      questionnaire is an appropriate tool to assess social participation in
      rehabilitation for native Malay language speakers.

PMID- 26288235
TI  - Fall-Related Injuries in a Cohort of Community-Dwelling Older Adults Attending
      Peer-Led Fall Prevention Exercise Classes.
AB  - BACKGROUND AND PURPOSE: To investigate reported injuries and circumstances and to
      estimate the costs related to falls experienced by older adults participating in
      Steady As You Go (SAYGO) peer-led fall prevention exercise classes. METHODS: A 12
      month prospective cohort study of 207 participants attending community-based
      SAYGO classes in Dunedin, New Zealand. Types and costs of medical treatment for
      injuries and circumstances of falls were obtained via standardized fall event
      questionnaires and phone-administered questionnaires. RESULTS: Eighty-four
      percent completed the study (160 females, 14 males, mean age = 77.5 [standard
      deviation = 6.5] years). More than a third of the total falls (55/148 total
      falls, 37%) did not result in any injuries. Most injuries (45%, n = 67) were
      sprains, grazes, and bruises. Medical attention was sought 26 times (18%), out of
      which 6 participants (4%) reported fractures (none femoral). The majority of
      falls occurred while walking. More falls and injuries occurred outdoors (n = 55).
      The number of times medical treatment was sought correlated with the number of
      falls in the previous year (r = 0.50, P = .02). The total number of years
      attending SAYGO was a significant predictor of lower total number of injuries
      (stepwise regression beta = -0.157, t = -1.99, P = .048). The total cost of
      medical treatment across all reported injurious falls was estimated at NZ$6946
      (US$5415). DISCUSSION: Older adults participating in SAYGO appear to sustain less
      severe injuries following a fall than previously reported. More falls and
      injuries occurred outdoors, suggesting better overall health of these
      participants. The role of long-term participation in fall prevention exercise
      classes on injurious falls warrants further investigation.

PMID- 26288236
TI  - Is the Veterans Specific Activity Questionnaire Valid to Assess Older Adults
      Aerobic Fitness?
AB  - BACKGROUND: Aerobic fitness in older adults is related to health status, incident
      disability, nursing home admission, and all-cause mortality. The most accurate
      quantification of aerobic fitness, expressed as peak oxygen consumption in
      mL.kg.min, is the cardiorespiratory exercise test; however, it is not feasible in
      all settings and might offer risk to patients. The Veterans Specific Activity
      Questionnaire (VSAQ) is a 13-item self-administered symptom questionnaire that
      estimates aerobic fitness expressed in metabolic equivalents (METs) and has been
      validated to cardiovascular patients. PURPOSE: The purpose of this study was to
      assess the validity and reliability of the VSAQ in older adults without specific
      health conditions. METHODS: A methodological study with a cross-sectional design
      was conducted with 28 older adults (66-86 years). The VSAQ was administered on 3
      occasions by 2 evaluators. Aerobic capacity in METs as measured by the VSAQ was
      compared with the METs found in an incremental shuttle walk test (ISWT) performed
      with a portable metabolic measurement system and with accelerometer data.
      RESULTS: The validity of the VSAQ was found to be moderate-to-good when compared
      with the METs and distance measured by the ISWT and with the moderate activity
      per day and steps per day obtained by accelerometry. The Bland-Altman graph
      analysis showed no values outside the limits of agreement, suggesting good
      precision between the METs estimated by questionnaire and the METs measured by
      the ISWT. Also, the intrarater and interrater reliabilities of the instrument
      were good. CONCLUSIONS: The results showed that the VSAQ is a valuable tool to
      assess the aerobic fitness of older adults.

PMID- 26288237
TI  - Measurements of Weight Bearing Asymmetry Using the Nintendo Wii Fit Balance Board
      Are Not Reliable for Older Adults and Individuals With Stroke.
AB  - BACKGROUND: Clinicians and researchers have used bathroom scales, balance
      performance monitors with feedback, postural scale analysis, and force platforms
      to evaluate weight bearing asymmetry (WBA). Now video game consoles offer a novel
      alternative for assessing this construct. By using specialized software, the
      Nintendo Wii Fit balance board can provide reliable measurements of WBA in
      healthy, young adults. However, reliability of measurements obtained using only
      the factory settings to assess WBA in older adults and individuals with stroke
      has not been established. PURPOSE: To determine whether measurements of WBA
      obtained using the Nintendo Wii Fit balance board and default settings are
      reliable in older adults and individuals with stroke. METHODS: Weight bearing
      asymmetry was assessed using the Nintendo Wii Fit balance board in 2 groups of
      participants-individuals older than 65 years (n = 41) and individuals with stroke
      (n = 41). Participants were given a standardized set of instructions and were not
      provided auditory or visual feedback. Two trials were performed. Intraclass
      correlation coefficients (ICC), standard error of measure (SEM), and minimal
      detectable change (MDC) scores were determined for each group. RESULTS: The ICC
      for the older adults sample was 0.59 (0.35-0.76) with SEM95 = 6.2% and MDC95 =
      8.8%. The ICC for the sample including individuals with stroke was 0.60 (0.47
      0.70) with SEM95 = 9.6% and MDC95 = 13.6%. DISCUSSION: Although measurements of
      WBA obtained using the Nintendo Wii Fit balance board, and its default factory
      settings, demonstrate moderate reliability in older adults and individuals with
      stroke, the relatively high associated SEM and MDC values substantially reduce
      the clinical utility of the Nintendo Wii Fit balance board as an assessment tool
      for WBA. CONCLUSIONS: Weight bearing asymmetry cannot be measured reliably in
      older adults and individuals with stroke using the Nintendo Wii Fit balance board
      without the use of specialized software.

PMID- 26288238
TI  - A Prospective Cohort Study on the Effect of a Balance Training Program, Including
      Calf Muscle Strengthening, in Community-Dwelling Older Adults.
AB  - BACKGROUND: Falls are the number 1 cause of injury, fractures, and death among
      the older population. In fact, one-third of adults older than 60 years will
      experience 1 or more falls annually. Factors including inactivity and decreased
      mobility are associated with overall declines in strength, balance, and
      functional mobility in older adults. PURPOSE: The purpose of this study was to
      evaluate the effect of a balance training program, including calf muscle
      strengthening, in community-dwelling older adults and to evaluate how calf muscle
      strength correlates with risk factors for falls. METHODS: Community-dwelling
      older adults from a local senior center were invited to participate in a 5-week
      (10 sessions), 1-on-1, balance training program, which included calf muscle
      strengthening. All the participants were evaluated before and after the
      intervention. The outcome measures were static balance, unilateral heel-rise
      test, Timed Up and Go test (TUG), the 30-second Chair Stand Test (30-sCST), and
      the Activity Balance Confidence Scale. RESULTS: Twenty-eight participants (6
      males and 22 females) mean (standard deviation) age of 78 years were included in
      the study and completed the baseline evaluation. Eight participants did not
      complete the study. Static balance with eyes closed, heel rise, TUG, 30-sCST, and
      the Activity Balance Confidence Scale improved significantly (P < .05) following
      treatment compared with the baseline evaluation. The heel-rise ability correlated
      significantly (P < .05) with TUG (r = -0.484 to -0.528) and 30-sCST (r = 0.501
      0.595). Sixty-three percent of the participants performed 10 reps or less of the
      unilateral heel rise on the right side and 60% on the left side. None of the
      participants who performed 10 reps or more of the unilateral heel rise had a high
      risk of falls based on the TUG. CONCLUSIONS: A balance training program that
      includes calf muscle strengthening performed twice a week for 5 weeks resulted in
      significant improvements in calf muscle strength, functional performance and
      balance, as well as a significant improvement in balance confidence. The results
      from this study identify the importance unilateral calf muscle strength has to
      falls risk among older adults.

PMID- 26288239
TI  - Gene Function Prediction from Functional Association Networks Using Kernel
      Partial Least Squares Regression.
AB  - With the growing availability of large-scale biological datasets, automated
      methods of extracting functionally meaningful information from this data are
      becoming increasingly important. Data relating to functional association between
      genes or proteins, such as co-expression or functional association, is often
      represented in terms of gene or protein networks. Several methods of predicting
      gene function from these networks have been proposed. However, evaluating the
      relative performance of these algorithms may not be trivial: concerns have been
      raised over biases in different benchmarking methods and datasets, particularly
      relating to non-independence of functional association data and test data. In
      this paper we propose a new network-based gene function prediction algorithm
      using a commute-time kernel and partial least squares regression (Compass). We
      compare Compass to GeneMANIA, a leading network-based prediction algorithm, using
      a number of different benchmarks, and find that Compass outperforms GeneMANIA on
      these benchmarks. We also explicitly explore problems associated with the non
      independence of functional association data and test data. We find that a
      benchmark based on the Gene Ontology database, which, directly or indirectly,
      incorporates information from other databases, may considerably overestimate the
      performance of algorithms exploiting functional association data for prediction. 

PMID- 26288240
TI  - Modification of Sunlight Radiation through Colored Photo-Selective Nets Affects
      Anthocyanin Profile in Vaccinium spp. Berries.
AB  - OBJECTIVES: In recent years, the interest on the effects of the specific
      wavelengths of the light spectrum on growth and metabolism of plants has been
      increasing markedly. The present study covers the effect of modified sunlight
      conditions on the accumulation of anthocyanin pigments in two Vaccinium species:
      the European wild bilberry (V. myrtillus L.) and the cultivated highbush
      blueberry (V. corymbosum L.). METHODS: The two Vaccinium species were grown in
      the same test field in the Alps of Trentino (Northern Italy) under modified light
      environment. The modification of sunlight radiation was carried out in field,
      through the use of colored photo-selective nets throughout the berry ripening
      during two consecutive growing seasons. The anthocyanin profile was then assessed
      in berries at ripeness. RESULTS: The results indicated that the light responses
      of the two Vaccinium species studied were different. Although both studied
      species are shade-adapted plants, 90% shading of sunlight radiation was
      beneficial only for bilberry plants, which accumulated the highest content of
      anthocyanins in both seasons. The same condition, instead, was not favorable for
      blueberries, whose maturation was delayed for at least two weeks, and anthocyanin
      accumulation was significantly decreased compared to berries grown under sunlight
      conditions. Moreover, the growing season had strong influence on the anthocyanin
      accumulation in both species, in relation to temperature flow and sunlight
      spectra composition during the berry ripening period. CONCLUSIONS: Our results
      suggest that the use of colored photo-selective nets may be a complementary
      agricultural practice for cultivation of Vaccinium species. However, further
      studies are needed to analyze the effect of the light spectra modifications to
      other nutritional properties, and to elucidate the molecular mechanisms behind
      the detected differences between the two relative Vaccinium species.

PMID- 26288242
TI  - Self-assembly of Thiolato-Bridged Manganese(I)-Based Metallarectangles: One-pot
      Synthesis and Structural Characterization.
AB  - A new series of thiolato-bridged manganese(I)-based supramolecular rectangles
      have been achieved by three-precursor self-assembly of Mn2(CO)10, diaryl
      disulfides (RSSR), and linear ditopic azine ligands (L) [L = pyrazine (pz), 4,4'
      bipyridine (bpy), and trans-1,2-bis(4-pyridyl)ethylene (bpe)] using a one-pot
      synthetic strategy. Oxidative addition of RSSR (diphenyl disulfide and p-tolyl
      disulfide) to manganese decacarbonyl in the presence of rigid bidentate ligands
      (L) afforded metallarectangles of the general formula [{(CO)3Mn(MU
      SR)2Mn(CO)3}2(MU-L)2] (1-6). Compounds 1-6 were characterized using elemental
      analyses and NMR, IR, and UV-vis absorption spectroscopic techniques. The
      molecular structures of metallarectangles 1, 3, and 5 were elucidated by single
      crystal X-ray diffraction methods. The guest binding ability of 3 and 5 has been
      investigated with two aromatic guests using electronic absorption and
      fluorescence emission spectroscopy, and the results revealed a strong binding
      interaction between host-guest species. 

PMID- 26288241
TI  - Association of MDR1 gene (C3435T) polymorphism and gene expression profiling in
      lung cancer patients treated with platinum-based chemotherapy.
AB  - INTRODUCTION: Chemotherapy is the standard and recommended treatment for lung
      cancer apart from surgery and radiotherapy. Chemotherapy is administered as mono
      agents or as combination therapy. In this study, we examined the role of MDR1
      C3435T polymorphisms in lung cancer patients undergoing chemotherapy. METHODS AND
      RESULTS: We genotyped 126 cases with lung cancer and 111 healthy controls, using
      the polymerase chain reaction-restriction fragment length polymorphism method
      (PCR-RFLP). Frequencies of MDR1 C3435C, C3435T and T3435T genotypes were 61, 16
      and 23 % in lung cancer patients and 86, 9 and 5 % in the controls, respectively.
      The T3435T genotypes had a 5.23-fold increased risk for lung cancer. (OR 5.23; 95
      % CI 2.082-13.146; p = 0.0004). Patients with TT genotypes were more frequent in
      stage IV and were significantly associated with the disease (p = 0.05). Habitual
      smoker lung cancer patients were 50 % CC genotypes whereas TT genotypes were 34
      %. The non-smokers had 46 % CC genotypes and 23 % TT genotypes. Furthermore, we
      collected tissue biopsy samples for expression analysis from 20 patients (for
      controls we used the non-cancerous region of the same tissue). The present study
      showed mRNA expression of MDR1 was up-regulated in 80 % of the cancer group in
      comparison with the control group (p = 0.0002). We also correlated the
      association between MDR1 genotypes with different combinations of chemotherapy.
      The combinations and genotype distributions in the group receiving paclitaxel +
      cisplatin were as follows: CC (67 %), CT (24 %) and TT (9 %) genotypes,
      respectively, and the group receiving carboplatin + gemcitabine CC (46 %), CT (19
      %) and TT (35 %) genotypes, respectively. We found that MDR1 (rs1045642) C3435T
      polymorphism and gene expression was significantly associated with the clinical
      outcome in lung carcinoma patients. CONCLUSION: In conclusion, it is suggested
      that MDR1 TT genotypes had higher risk for the development of lung cancer. Also,
      this polymorphism could be used as a genetic marker for predicting the clinical
      outcome of lung cancer patients.

PMID- 26288243
TI  - Subtype distribution of hepatitis C virus in Jiangsu, China.
AB  - Hepatitis C virus (HCV) genotype distribution varied by regions and transmission
      modes. In this study, we investigated HCV genotype distribution in five cities of
      Jiangsu, China, all of which are located in the Yangtze River Delta Region. A
      total of 363 samples were collected during 2011-2012. C/E2 and NS5B fragments of
      HCV were amplified using a multiple RT-nested PCR strategy and subjected to
      sequencing. Phylogenetic analysis was performed for HCV genotyping. Among 106 PCR
      positive cases, HCV subtypes 1a (0.9%), 1b (61.3%), 2a (15.1%), 3a (4.7%), 3b
      (9.4%), 6a (6.6%), and 6n (1.9%) were detected. Together with our previous data,
      we found that HCV subtypes were more among injection drug users (IDUs) (nine)
      than among general population (GP) (six), and the most common subtype among GP
      was 1b (73.9%), followed by 2a (14.5%), while the top four common subtypes among
      IDUs were 3a, 1b, 3b, and 6a, with similar prevalence rates (24.4%, 22.7%, 20.9%,
      and 17.4%, respectively). There were nine HCV subtypes prevalent among IDUs in
      Jiangsu, more than those in Xinjiang, Hubei, Yunnan, Guangxi, Guangdong, and Hong
      Kong. The top four common subtypes among IDUs in Jiangsu covered all the two most
      common HCV subtypes (except 6n subtype) observed in six targeted
      provinces/region. These results suggested that Jiangsu may be an important
      gathering place for various HCV subtypes and the gathering may be involved in the
      large scale of population migration from other regions of China to Eastern China.

PMID- 26288244
TI  - Niche partitioning and environmental factors affecting abundance of
      strepsirrhines in Angola.
AB  - The African nocturnal primates (galagos, pottos, and angwantibos: suborder
      Strepsirrhini) are the result of the first major primate radiation event in
      Africa, and are found in different primate communities spread across the entire
      sub-Saharan Africa. Thus, they represent an interesting group of taxa to
      investigate community strategies to avoid interspecific competition. Here, we
      present the result of the first study on nocturnal primate communities in western
      Angola. We aimed to identify habitat factors influencing strepsirrhine abundance,
      collect evidence of spatial niche segregation, and discuss possible indications
      of competitive exclusion in this region. We conducted nocturnal surveys at four
      study sites: Kumbira, Bimbe, Northern Scarp, and Calandula. At each encounter we
      recorded species, group size, height of animals above ground, and GPS location.
      We sampled vegetation using the point-centered quarter method and collected data
      on canopy cover, disturbance, and undergrowth density. We observed a total of
      five strepsirrhine species with varying community structures. We did not
      encounter Galagoides thomasi but we recorded a new species Galagoides sp. nov. 4.
      Levels of disturbance, canopy cover and undergrowth density were the habitat
      factors that most influenced variation in abundance of Galagoides demidovii and
      Perodicticus edwardsi, the latter also preferring the habitat with higher tree
      density. Vertical separation between sympatric strepsirrhines was strongest in
      Northern Scarp, where overall relative abundance was also highest. Competitive
      exclusion between G. thomasi and G. sp. nov. 4 may explain why the former was not
      present within the Angolan Escarpment sites. We observed coexistence between
      mainly allopatric Otolemur crassicaudatus and P. edwardsi in Kumbira, and of
      Galago moholi and G. demidovii in Calandula. Both unusual combinations showed
      some levels of spatial segregation. Habitat characteristics of the Escarpment
      region are likely to allow for unique nocturnal primate species assemblages. We
      urge immediate conservation interventions in the Angolan Escarpment.

PMID- 26288245
TI  - Thecamoebians (Testate Amoebae) Straddling the Permian-Triassic Boundary in the
      Guryul Ravine Section, India: Evolutionary and Palaeoecological Implications.
AB  - Exceptionally well-preserved organic remains of thecamoebians (testate amoebae)
      were preserved in marine sediments that straddle the greatest extinction event in
      the Phanerozoic: the Permian-Triassic Boundary. Outcrops from the Late Permian
      Zewan Formation and the Early Triassic Khunamuh Formation are represented by a
      complete sedimentary sequence at the Guryul Ravine Section in Kashmir, India,
      which is an archetypal Permian-Triassic boundary sequence. Previous
      biostratigraphic analysis provides chronological control for the section, and a
      perspective of faunal turnover in the brachiopods, ammonoids, bivalves,
      conodonts, gastropods and foraminifera. Thecamoebians were concentrated from bulk
      sediments using palynological procedures, which isolated the organic constituents
      of preserved thecamoebian tests. The recovered individuals demonstrate
      exceptional similarity to the modern thecamoebian families Centropyxidae,
      Arcellidae, Hyalospheniidae and Trigonopyxidae, however, the vast majority belong
      to the Centropyxidae. This study further confirms the morphologic stability of
      the thecamoebian lineages through the Phanerozoic, and most importantly, their
      apparent little response to an infamous biological crisis in Earth's history.

PMID- 26288246
TI  - Antidepressant Response Trajectories and Associated Clinical Prognostic Factors
      Among Older Adults.
AB  - IMPORTANCE: More than 50% of older adults with late-life major depressive
      disorder fail to respond to initial treatment with first-line pharmacological
      therapy. OBJECTIVES: To assess typical patterns of response to an open-label
      trial of extended-release venlafaxine hydrochloride (venlafaxine XR) for late
      life depression and to evaluate which clinical factors are associated with the
      identified longitudinal response patterns. DESIGN, SETTING, AND PARTICIPANTS:
      Group-based trajectory modeling was applied to data from a 12-week open-label
      pharmacological trial conducted in specialty care as part of the Incomplete
      Response in Late Life: Getting to Remission Study. Clinical prognostic factors,
      including domain-specific cognitive performance and individual depression
      symptoms, were examined in relation to response trajectories. Participants
      included 453 adults aged 60 years or older with current major depressive
      disorder. The study was conducted between August 2009 and August 2014.
      INTERVENTION: Open-label venlafaxine XR (titrated up to 300 mg/d) for 12 weeks.
      MAIN OUTCOMES AND MEASURES: Subgroups exhibiting similar response patterns were
      derived from repeated measures of overall depression severity obtained using the
      Montgomery-Asberg Depression Rating Scale. RESULTS: Among the 453 study
      participants, 3 subgroups with differing baseline depression severity clearly
      responded to treatment: one group with the lowest baseline severity had a rapid
      response (n = 69 [15.23%]), and distinct responses were also apparent among
      groups starting at moderate (n = 108 [23.84%]) and higher (n = 25 [5.52%])
      baseline symptom levels. Three subgroups had nonresponding trajectories: 2 with
      high baseline symptom levels (totaling 35.98%: high, nonresponse 1, n = 110
      [24.28%]; high, nonresponse 2, n = 53 [11.70%]) and 1 with moderate baseline
      symptom levels (n = 88 [19.43%]). Several factors were independently associated
      with having a nonresponsive trajectory, including greater baseline depression
      severity, longer episode duration, less subjective sleep loss, more guilt, and
      more work/activity impairment (P < .05). Higher delayed memory (list recognition)
      performance was independently associated with having a rapid response (adjusted
      odds ratio = 2.22; 95% CI, 1.18-4.20). CONCLUSIONS AND RELEVANCE: Based on the
      observed trajectory patterns, patients who have late-life depression with high
      baseline depression severity are unlikely to respond after 12 weeks of treatment
      with venlafaxine XR. However, high baseline depression severity alone may be
      neither a necessary nor sufficient predictor of treatment nonresponse. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00892047.

PMID- 26288247
TI  - Facilitation effect of observed motor deviants in a cooperative motor task:
      Evidence for direct perception of social intention in action.
AB  - Spatiotemporal parameters of voluntary motor action may help optimize human
      social interactions. Yet it is unknown whether individuals performing a
      cooperative task spontaneously perceive subtly informative social cues emerging
      through voluntary actions. In the present study, an auditory cue was provided
      through headphones to an actor and a partner who faced each other. Depending on
      the pitch of the auditory cue, either the actor or the partner were required to
      grasp and move a wooden dowel under time constraints from a central to a lateral
      position. Before this main action, the actor performed a preparatory action under
      no time constraint, consisting in placing the wooden dowel on the central
      location when receiving either a neutral ("pret"-ready) or an informative
      auditory cue relative to who will be asked to perform the main action (the actor:
      "moi"-me, or the partner: "lui"-him). Although the task focused on the main
      action, analysis of motor performances revealed that actors performed the
      preparatory action with longer reaction times and higher trajectories when
      informed that the partner would be performing the main action. In this same
      condition, partners executed the main actions with shorter reaction times and
      lower velocities, despite having received no previous informative cues. These
      results demonstrate that the mere observation of socially driven motor actions
      spontaneously influences the low-level kinematics of voluntary motor actions
      performed by the observer during a cooperative motor task. These findings
      indicate that social intention can be anticipated from the mere observation of
      action patterns. 

PMID- 26288248
TI  - Updates on the Construction of an Eyeglass-Supported Nasal Prosthesis Using
      Computer-Aided Design and Rapid Prototyping Technology.
AB  - This study was undertaken to design an updated connection system for an eyeglass
      supported nasal prosthesis using rapid prototyping techniques. The substructure
      was developed with two main endpoints in mind: the connection to the silicone and
      the connection to the eyeglasses. The mold design was also updated; the mold was
      composed of various parts, each carefully designed to allow for easy release
      after silicone processing and to facilitate extraction of the prosthesis without
      any strain. The approach used in this study enabled perfect transfer of the
      reciprocal position of the prosthesis with respect to the eyeglasses, from the
      virtual to the clinical environment. Moreover, the reduction in thickness
      improved the flexibility of the prosthesis and promoted adaptation to the
      contours of the skin, even during functional movements. The method described here
      is a simplified and viable alternative to standard construction techniques for
      nasal prostheses and offers improved esthetic and functional results when no bone
      is available for implant-supported prostheses. 

PMID- 26288250
TI  - On-chip phase measurement for microparticles trapped on a waveguide.
AB  - Polystyrene microparticles are trapped on a waveguide Young interferometer and
      the phase change caused by the trapped particles is measured. This is a novel, on
      chip method that can be used to count and characterize trapped particles. The
      trapping of single particles is clearly identified. Simulations show that the
      phase change increases with the diameter up to 7 MUm, while for larger particles,
      morphology-dependent resonances appear. For 7 MUm particles, a phase change of 
      0.13 rad is measured, while the simulated value is -0.28 rad. Extensive
      simulations are carried out regarding the phase change, waveguide transmission
      and the forces on the particles, and also regarding sources of the discrepancy
      between simulations and measurements. 

PMID- 26288249
TI  - Variability of Gene Expression Identifies Transcriptional Regulators of Early
      Human Embryonic Development.
AB  - An analysis of gene expression variability can provide an insightful window into
      how regulatory control is distributed across the transcriptome. In a single cell
      analysis, the inter-cellular variability of gene expression measures the
      consistency of transcript copy numbers observed between cells in the same
      population. Application of these ideas to the study of early human embryonic
      development may reveal important insights into the transcriptional programs
      controlling this process, based on which components are most tightly regulated.
      Using a published single cell RNA-seq data set of human embryos collected at four
      cell, eight-cell, morula and blastocyst stages, we identified genes with the most
      stable, invariant expression across all four developmental stages. Stably
      expressed genes were found to be enriched for those sharing indispensable
      features, including essentiality, haploinsufficiency, and ubiquitous expression.
      The stable genes were less likely to be associated with loss-of-function variant
      genes or human recessive disease genes affected by a DNA copy number variant
      deletion, suggesting that stable genes have a functional impact on the regulation
      of some of the basic cellular processes. Genes with low expression variability at
      early stages of development are involved in regulation of DNA methylation,
      responses to hypoxia and telomerase activity, whereas by the blastocyst stage,
      low-variability genes are enriched for metabolic processes as well as telomerase
      signaling. Based on changes in expression variability, we identified a putative
      set of gene expression markers of morulae and blastocyst stages. Experimental
      validation of a blastocyst-expressed variability marker demonstrated that HDDC2
      plays a role in the maintenance of pluripotency in human ES and iPS cells.
      Collectively our analyses identified new regulators involved in human embryonic
      development that would have otherwise been missed using methods that focus on
      assessment of the average expression levels; in doing so, we highlight the value
      of studying expression variability for single cell RNA-seq data. 

PMID- 26288251
TI  - Design of high-performance anti-adhesion agent using injectable gel with an anti
      oxidative stress function.
AB  - Postsurgical tissue adhesion formation caused by inflammation and oxidative
      stress is one of the serious issues because it induces severe clinical disorders.
      In this study, we designed redox injectable gel (RIG) which covalently possesses
      nitroxide radicals as a reactive oxygen species (ROS) scavenger for high
      performance anti-adhesion agent. The redox flower micelles exhibiting gelation
      under physiological conditions were prepared by a polyion complex (PIC) between
      polyamine-PEG-polyamine triblock copolymer possessing nitroxide radicals as a
      side chain of polyamine segments and poly(acrylic acid). RIG showed prolonged
      local retention in the abdominal cavity of the mice, which was monitored by in
      vivo imaging system (IVIS). Compared with a commercial anti-adhesion agent
      (Seprafilm((r)), Genzyme, Cambridge, MA), RIG dramatically inhibited the
      formation of tissue adhesions via a combination of physical separation and
      biological elimination of generated ROS in talc-induced adhesion model mice.
      Treatment with RIG suppressed inflammatory cytokines and neutrophil invasion,
      suppressing the increase in peritoneal membrane thickness. It is also emphasized
      that RIG suppressed the increase of white blood cells level, indicating that the
      present RIG treatment effectively prevents diffusion of local inflammation to
      entire body. These findings indicate that RIG has a great potential as a high
      performance anti-adhesion agent. 

PMID- 26288252
TI  - The Risk of Cyanobacterial Toxins in Dialysate: What Do We Know?
AB  - Surface waters are increasingly contaminated by cyanobacteria, which may produce
      potent cyanotoxins harmful to animals and humans. Hemodialysis patients are at
      high risk of injury from waterborne contaminants in the water used to prepare
      dialysate. Episodes of acute illness and death among hemodialysis patients have
      been reported following exposure to dialysate prepared from drinking water
      contaminated with elevated concentrations of cyanotoxins. Protecting dialysis
      patients from these toxins is complicated by a lack of monitoring and regulation
      of cyanotoxins in drinking water, uncertainty as to their safe levels in
      dialysate, and incomplete knowledge of how well current dialysate preparation and
      water treatment practices remove them. Until these issues are adequately
      addressed, hemodialysis centers should be aware of the potential for cyanotoxins
      to be present in their potable water supply, particularly when it comes from
      surface water sources prone to cyanobacterial blooms. 

PMID- 26288253
TI  - Measuring Recovery in Elite Rugby Players: The Brief Assessment of Mood,
      Endocrine Changes, and Power.
AB  - PURPOSE: There is demand in applied sport settings to measure recovery briefly
      and accurately. Research indicates mood disturbance as the strongest
      psychological predictor of mental and physical recovery. The Brief Assessment of
      Mood (BAM) is a shortened version of the Profile of Mood States that can be
      completed in less than 30 s. The purpose of this study was to examine the BAM as
      a quick measure of mood in relation to recovery status in elite rugby players
      alongside established physiological markers of recovery. METHOD: Using elite
      rugby union players (N = 12), this study examined the utility of BAM as an
      indicator of mental and physical recovery in elite athletes by exploring pattern
      change in mood disturbance, energy index, power output, cortisol, and
      testosterone 36 hr before and 12 hr, 36 hr, and 60 hr after a competitive rugby
      match. RESULTS: Repeated-measures multivariate analysis of variance indicated
      significant changes in all variables across the 4 time points (p < .05, eta(2)
      range = .20-.48), concurrent with previous study findings. Although visual
      inspection of the graphs indicated that the pattern of change for mood
      disturbance and energy index mapped changes in all physiological variables, only
      a low correlation was observed for power output (r = - .34). CONCLUSIONS:
      Although BAM scores changed significantly over time in accordance with the
      hypotheses, further testing is required to confirm the utility of the BAM as a
      measure of recovery. The results indicate that the BAM could be used as 1
      indicator of recovery status alongside other measures.

PMID- 26288254
TI  - Insulin resistance and beta-cell function influence postprandial blood glucose
      levels in Japanese patients with gestational diabetes mellitus.
AB  - AIMS/INTRODUCTION: The aim of this study in patients with gestational diabetes
      mellitus (GDM) was to evaluate the relationship of insulin resistance and
      secretion to area-under-the-sensor glucose concentration-time curve from before
      to 120 min postmeal (CGM-AUC(0-120 min)) as determined with continuous glucose
      monitoring (CGM). MATERIALS AND METHODS: Immunoreactive insulin and HbA1c were
      determined in 22 Japanese patients with GDM undergoing a 75 g oral glucose
      tolerance test. Patients underwent CGM within 3 weeks of receiving a diagnosis of
      GDM. RESULTS: HbA1c (NGSP) was 5.5 +/- 0.4%, BMI was 24.8 +/- 5.3 kg/m(2), mean
      sensor glucose by CGM was 94.2 +/- 10.3 mg/dL, standard deviation was 17.5 +/-
      4.4 mg/dL, and CGM-AUC(0-120 min) was 204.2 +/- 23.8 h mg/dL. The insulin
      resistance indices the homeostasis model assessment ratio (HOMA-R), quantitative
      insulin sensitivity check index (QUICKI), and the Matsuda Index were correlated
      with CGM-AUC(0-120 min). The disposition index (DI), which was used to evaluate
      insulin secretion, was negatively correlated with CGM-AUC(0-120 min).
      CONCLUSIONS: Not only insulin resistance but also beta cell dysfunction
      contributes to postprandial hyperglycemia in Japanese patients with GDM.

PMID- 26288255
TI  - Caregiver education to promote appropriate use of preventive asthma medications:
      what is happening in primary care?
AB  - OBJECTIVE: To describe actions taken by providers at primary care visits to
      promote daily use of preventive asthma medication, and determine whether patient
      or encounter variables are associated with the receipt of asthma medication
      education. METHODS: As part of a larger study in Rochester, NY, caregivers of
      children (2-12 years old) with asthma were approached before an office visit for
      well-child, asthma-specific or other illness care from October 2009 to January
      2013. Eligibility required persistent symptoms and a prescription for an inhaled
      asthma controller medication. Caregivers were interviewed within two weeks to
      discuss the health care encounter. RESULTS: We identified 185 eligible children
      from six urban primary care offices (27% Black, 38% Hispanic, 65% Medicaid).
      Overall, 42% of caregivers reported a discussion of appropriate preventive
      medication use, fewer than 25% received an asthma action plan, and 17% reported
      "ideal" medication education (both discussing proper medication use and
      completing an asthma action plan); no differences were seen upon comparing well
      child and asthma-specific visits with other visits. Well-child and asthma
      specific visits together were more likely, compared with other visits, to include
      a recommendation for a follow-up visit (43% versus 23%, p = 0.007). No patient
      factors were associated with report of preventive medication education.
      CONCLUSIONS: Guideline-recommended education for caregivers about preventive
      asthma medication is not occurring in the majority of primary care visits for
      urban children with symptomatic persistent asthma. Novel methods to deliver
      asthma education may be needed to promote appropriate preventive medication use
      and reduce asthma morbidity.

PMID- 26288257
TI  - Emerging Infections Program--20 Years of Achievements and Future Prospects.

PMID- 26288258
TI  - Weight management practices and evidence for weight loss through primary care: a
      brief review.
AB  - OBJECTIVE: The optimal role for primary care in the management of overweight and
      obesity is yet to be determined. This review examines current weight management
      practices in primary care and summarizes the evidence for weight loss
      interventions based in primary care settings. RESEARCH DESIGN AND METHODS: PubMed
      was searched for literature on weight management in primary care published from
      2000 onwards. Forty-one articles were included. RESULTS: The prevalence of
      overweight and obesity is high among primary care patients, yet frequently under
      diagnosed by general practitioners. When diagnosed, weight management practices
      are highly variable. Evidence supporting effective long term interventions for
      weight loss in primary care is limited. Consistency of outcome measures, explicit
      reporting of attrition rates and assessment of motivation at inclusion are
      critical for interpreting results. CONCLUSIONS: An approach to weight management
      that includes the involvement of disciplines other than general practice appears
      to be more successful. Further research is required to determine the most
      effective approach in primary care.

PMID- 26288256
TI  - Interferon-gamma enhances both the anti-bacterial and the pro-inflammatory
      response of human mast cells to Staphylococcus aureus.
AB  - Human mast cells (huMCs) are involved in both innate and adaptive immune
      responses where they release mediators including amines, reactive oxygen species
      (ROS), eicosanoids and cytokines. We have reported that interferon-gamma (IFN
      gamma) enhances FcgammaR-dependent ROS production. The aim of this study was to
      extend these observations by investigating the effect of IFN-gamma on the
      biological responses of huMCs to Staphylococcus aureus. We found that exposure of
      huMCs to S. aureus generated intracellular and extracellular ROS, which were
      enhanced in the presence of IFN-gamma. IFN-gamma also promoted bacteria killing,
      beta-hexosaminidase release and eicosanoid production. Interferon-gamma similarly
      increased expression of mRNAs encoding CCL1 to CCL4, granulocyte-macrophage
      colony-stimulating factor (GM-CSF), tumour necrosis factor-alpha and CXCL8 in S.
      aureus-stimulated huMCs. The ability of IFN-gamma to increase CXCL8 and GM-CSF
      protein levels was confirmed by ELISA. Fibronectin or a beta1 integrin blocking
      antibody completely abrogated IFN-gamma-dependent S. aureus binding and reduced
      S. aureus-dependent CXCL8 secretion. These data demonstrate that IFN-gamma primes
      huMCs for enhanced anti-bacterial and pro-inflammatory responses to S. aureus,
      partially mediated by beta1 integrin.

PMID- 26288259
TI  - An Efficient Approach to Evaluate Reporter Ion Behavior from MALDI-MS/MS Data for
      Quantification Studies Using Isobaric Tags.
AB  - Protein quantification, identification, and abundance determination are important
      aspects of proteome characterization and are crucial in understanding biological
      mechanisms and human diseases. Different strategies are available to quantify
      proteins using mass spectrometric detection, and most are performed at the
      peptide level and include both targeted and untargeted methodologies. Discovery
      based or untargeted approaches oftentimes use covalent tagging strategies (i.e.,
      iTRAQ, TMT), where reporter ion signals collected in the tandem MS experiment are
      used for quantification. Herein we investigate the behavior of the iTRAQ 8-plex
      chemistry using MALDI-TOF/TOF instrumentation. The experimental design and data
      analysis approach described is simple and straightforward, which allows
      researchers to optimize data collection and proper analysis within a laboratory.
      iTRAQ reporter ion signals were normalized within each spectrum to remove peptide
      biases. An advantage of this approach is that missing reporter ion values can be
      accepted for purposes of protein identification and quantification without the
      need for ANOVA analysis. We investigate the distribution of reporter ion peak
      areas in an equimolar system and a mock biological system and provide
      recommendations for establishing fold-change cutoff values at the peptide level
      for iTRAQ data sets. These data provide a unique data set available to the
      community for informatics training and analysis. 

PMID- 26288260
TI  - Multicomponent Synthesis and Biological Evaluation of a Piperazine-Based Dopamine
      Receptor Ligand Library.
AB  - A series of 1,4-disubstituted piperazine-based compounds were designed,
      synthesized, and evaluated as dopamine D2/D3 receptor ligands. The synthesis
      relies on the key multicomponent split-Ugi reaction, assessing its great
      potential in generating chemical diversity around the piperazine core. With the
      aim of evaluating the effect of such diversity on the dopamine receptor affinity,
      a small library of compounds was prepared, applying post-Ugi transformations.
      Ligand stimulated binding assays indicated that some compounds show a significant
      affinity, with K i values up to 53 nM for the D2 receptor. Molecular docking
      studies with the D2 and D3 receptor homology models were also performed on
      selected compounds. They highlighted key interactions at the indole head and at
      the piperazine moiety, which resulted in good agreement with the known
      pharmacophore models, thus helping to explain the observed structure-activity
      relationship data. Molecular insights from this study could enable a rational
      improvement of the split-Ugi primary scaffold, toward more selective ligands. 

PMID- 26288261
TI  - Photon-Upconverting Ionic Liquids: Effective Triplet Energy Migration in
      Contiguous Ionic Chromophore Arrays.
AB  - Inspired by the bicontinuous ionic-network structure of ionic liquids (ILs), we
      developed a new family of photofunctional ILs which show efficient triplet energy
      migration among contiguously arrayed ionic chromophores. A novel fluorescent IL,
      comprising an aromatic 9,10-diphenylanthracene 2-sulfonate anion and an alkylated
      phosphonium cation, showed pronounced interactions between chromophores, as
      revealed by its spectral properties. Upon dissolving a triplet sensitizer, the IL
      demonstrated photon upconversion based on triplet-triplet annihilation (TTA-UC).
      Interestingly, the TTA-UC process in the chromophoric IL was optimized at a much
      lower excitation intensity compared to the previous nonionic liquid TTA-UC
      system. The superior TTA-UC in this IL system is characterized by a relatively
      high triplet diffusion constant (1.63*10(-6) cm(2) s(-1)) which is ascribed to
      the presence of ionic chromophore networks in the IL.

PMID- 26288262
TI  - First-contact care with a medical vs chiropractic provider after consultation
      with a swiss telemedicine provider: comparison of outcomes, patient satisfaction,
      and health care costs in spinal, hip, and shoulder pain patients.
AB  - OBJECTIVE: The purpose of this study was to identify differences in outcomes,
      patient satisfaction, and related health care costs in spinal, hip, and shoulder
      pain patients who initiated care with medical doctors (MDs) vs those who
      initiated care with doctors of chiropractic (DCs) in Switzerland. METHODS: A
      retrospective double cohort design was used. A self-administered questionnaire
      was completed by first-contact care spinal, hip, and shoulder pain patients who,
      4 months previously, contacted a Swiss telemedicine provider regarding advice
      about their complaint. Related health care costs were determined in a subsample
      of patients by reviewing the claims database of a Swiss insurance provider.
      RESULTS: The study sample included 403 patients who had seen MDs and 316 patients
      who had seen DCs as initial health care providers for their complaint.
      Differences in patient sociodemographic characteristics were found in terms of
      age, pain location, and mode of onset. Patients initially consulting MDs had
      significantly less reduction in their numerical pain rating score (difference of
      0.32) and were significantly less likely to be satisfied with the care received
      (odds ratio = 1.79) and the outcome of care (odds ratio = 1.52). No significant
      differences were found for Patient's Global Impression of Change ratings. Mean
      costs per patient over 4 months were significantly lower in patients initially
      consulting DCs (difference of CHF 368; US $368). CONCLUSION: Spinal, hip, and
      shoulder pain patients had clinically similar pain relief, greater satisfaction
      levels, and lower overall cost if they initiated care with DCs, when compared
      with those who initiated care with MDs.

PMID- 26288263
TI  - Omega-3 Supplementation for Psychotic Mania and Comorbid Anxiety in Children.
AB  - OBJECTIVES: Therapeutic benefits of omega-3 fatty acids (Omega3) for mood
      disorders, psychosis, and anxiety have been reported in the literature. The
      purpose of the present article is to provide a literature review of Omega3
      supplementation for affective disorders and to illustrate the benefits of Omega3
      with a case presentation of a young girl with a history of bipolar disorder-type
      1 with psychotic features and generalized anxiety disorder. METHODS: Reviewed
      literature includes treatment studies of the impact of Omega3 on child mood
      disorders supplemented by review of meta-analyses within the adult mood disorders
      literature. The subject of this case report participated in 11 in-depth
      diagnostic and functional assessments over 5 years as part of an unrelated study.
      Three years were presupplementation and 2 years were with supplementation with no
      other medication changes, thus making a naturalistic multiple-baseline single
      subject experiment. RESULTS: Augmentation over a 2 year period was notable for
      clinically significant and sustained improvement in depressive, manic, and
      psychotic symptoms. CONCLUSION: Omega3 supplementation may be a safe, adjunct
      intervention for treating bipolar disorder in children and adolescents, even in
      the presence of psychotic and anxious features. The 2 year follow-up in this case
      offers hope of an accumulating and enduring benefit. Further research into
      mechanisms of Omega3 action and of combination treatment with other well-known
      interventions for mood disorders would be beneficial.

PMID- 26288264
TI  - Midterm results of percutaneous microwave ablation under ultrasound guidance
      versus retroperitoneal laparoscopic radial nephrectomy for small renal cell
      carcinoma.
AB  - Laparoscopic radial nephrectomy (LRN) and microwave ablation (MWA) are optional
      treatment for renal cell carcinoma (RCC). However, the comparative study with two
      techniques remains lacking. The aim of this study was to evaluate midterm results
      of MWA vs. LRN in patients with small RCC. A total of 426 patients with <= 4 cm
      RCC were included from April 2006 to October 2012. Ninety-eight patients
      underwent MWA and 328 patients LRN. The survival, recurrence, and renal function
      changes were compared between two treatments. Although overall survival after MWA
      (82.6% at 5 years) was lower than those after LRN (98.6% at 5 years, p = 0.0004),
      the RCC-related survival (97% at 5 years) was comparable to those following LRN
      (98% at 5 years, p = 0.38). One local tumor progress occurred at 32 months after
      MWA and none after LRN. The major complication rates were comparable between two
      techniques (1.7% in MWA vs. 1.5% in LRN, p = 0.75), but MWA showed less renal
      function damage than LRN (p < 0.0001). The multivariate analysis showed the
      presence of postablation extrarenal metastasis may become a predictor of the
      oncologic outcome (p = 0.059) and treatment modality had no influence (p =
      0.965). This study demonstrates that MWA and LRN provide comparable results in
      small RCC outcomes.

PMID- 26288265
TI  - Spectrum of IgG4-related disease on multi-detector CT: a 5-year study of a single
      medical center data.
AB  - PURPOSE: To discuss the diverse imaging features of pancreatic and extra
      pancreatic lesions of IgG4-related disease (IgG4-RD) on multi-detector CT (MDCT).
      METHODS: This retrospective study was approved by our institutional research
      ethics board, and informed consent was waived. From 2008 to 2013, 159 patients
      including 120 men (mean age 57 years; range 27-79 years) and 39 women (mean age
      51 years; range 25-83 years) who met the comprehensive diagnostic criteria for
      IgG4-RD (2011) were enrolled. MDCT images consisted of 153 abdominal images, 64
      pelvic images, 64 thoracic images, and 8 neck images were retrospectively
      analyzed in consensus by two radiologists with expertise in the CT diagnosis of
      IgG4-RD. RESULTS: Only 11 (11/153, 7.2%) IgG4-RD patients had been found with no
      pancreatic involvement. 145 (145/159, 91.2%) patients had various extra
      pancreatic lesions, including involvement of biliary tree (93/153, 60.8%), peri
      pancreatic vessels (66/153, 43.1%), IgG4-related lymphadenopathy, peri-abdominal
      aorta arteritis or retroperitoneal fibrosis, head and neck lesions, etc. Renal
      lesions were found in 26 (26/153, 17.0%) IgG4-RD patients with 4 types of renal
      parenchymal involvement. Lung lesions were found in 44 (44/64, 68.7%) IgG4-RD
      patients, which were classified into 7 types. CONCLUSIONS: Pancreatic and various
      extra-pancreatic lesions may be involved in IgG4-RD patients frequently with
      typical imaging findings. It is useful to recognize the atypical or uncommon
      imaging features to help the diagnosis of IgG4-RD together with other serologic
      or histopathologic findings.

PMID- 26288266
TI  - Medicinal Chemistry Approaches to Heart Regeneration.
AB  - Because of the minimal and clearly insufficient ability of the adult heart to
      regenerate after ischemic injury, there is a great opportunity to identify
      biological mechanisms, substances, and factors that enhance this process. Hence,
      innovative therapeutic management of heart failure following infarction requires
      a paradigm shift in pharmacotherapy. Spurred by tremendous progress in the field
      of stem cell and cardiac biology, several attractive approaches for regeneration
      of lost cardiomyocytes and supporting vasculature have emerged. Research in this
      area focuses on restoring the hearts' original function via proliferation and
      differentiation of cardiac progenitor cells, proliferation of pre-existing
      cardiomyocytes, and reprogramming of cardiac fibroblasts. In this review, we
      outline these principal strategies, putative biological targets or signaling
      pathways and chemical agents, with a focus on small molecules, to achieve
      therapeutic heart regeneration. We also point out the many remaining questions
      and challenges, particularly for translating in vitro discoveries to in vivo
      application. 

PMID- 26288268
TI  - Changing Trends in the U.S. Anesthesiology Workforce, with a Focus on Geographic
      Regions and Gender.

PMID- 26288269
TI  - Images in Anesthesiology: An Unexpected Embolism during a Craniotomy.

PMID- 26288267
TI  - Intubation Biomechanics: Laryngoscope Force and Cervical Spine Motion during
      Intubation in Cadavers-Cadavers versus Patients, the Effect of Repeated
      Intubations, and the Effect of Type II Odontoid Fracture on C1-C2 Motion.
AB  - BACKGROUND: The aims of this study are to characterize (1) the cadaver intubation
      biomechanics, including the effect of repeated intubations, and (2) the relation
      between intubation force and the motion of an injured cervical segment. METHODS:
      Fourteen cadavers were serially intubated using force-sensing Macintosh and
      Airtraq laryngoscopes in random order, with simultaneous cervical spine motion
      recorded with lateral fluoroscopy. Motion of the C1-C2 segment was measured in
      the intact and injured state (type II odontoid fracture). Injured C1-C2 motion
      was proportionately corrected for changes in intubation forces that occurred with
      repeated intubations. RESULTS: Cadaver intubation biomechanics were comparable
      with those of patients in all parameters other than C2-C5 extension. In cadavers,
      intubation force (set 2/set 1 force ratio = 0.61; 95% CI, 0.46 to 0.81; P =
      0.002) and Oc-C5 extension (set 2 - set 1 difference = -6.1 degrees; 95% CI, 
      11.4 to -0.9; P = 0.025) decreased with repeated intubations. In cadavers, C1-C2
      extension did not differ (1) between intact and injured states; or (2) in the
      injured state, between laryngoscopes (with and without force correction). With
      force correction, in the injured state, C1-C2 subluxation was greater with the
      Airtraq (mean difference 2.8 mm; 95% CI, 0.7 to 4.9 mm; P = 0.004). CONCLUSIONS:
      With limitations, cadavers may be clinically relevant models of intubation
      biomechanics and cervical spine motion. In the setting of a type II odontoid
      fracture, C1-C2 motion during intubation with either the Macintosh or the Airtraq
      does not appear to greatly exceed physiologic values or to have a high likelihood
      of hyperextension or direct cord compression.

PMID- 26288270
TI  - Creating an Anesthesiologist-run Pacemaker and Defibrillator Service: Closing the
      Perioperative Care Gap for These Patients.

PMID- 26288272
TI  - Sponge-Templated Macroporous Graphene Network for Piezoelectric ZnO
      Nanogenerator.
AB  - We report a simple approach to fabricate zinc oxide (ZnO) nanowire based
      electricity generators on three-dimensional (3D) graphene networks by utilizing a
      commercial polyurethane (PU) sponge as a structural template. Here, a 3D network
      of graphene oxide is deposited from solution on the template and then is
      chemically reduced. Following steps of ZnO nanowire growth, polydimethylsiloxane
      (PDMS) backfilling and electrode lamination completes the fabrication processes.
      When compared to conventional generators with 2D planar geometry, the sponge
      template provides a 3D structure that has a potential to increase power density
      per unit area. The modified one-pot ZnO synthesis method allows the whole process
      to be inexpensive and environmentally benign. The nanogenerator yields an open
      circuit voltage of ~0.5 V and short circuit current density of ~2 MUA/cm(2),
      while the output was found to be consistent after ~3000 cycles. Finite element
      analysis of stress distribution showed that external stress is concentrated to
      deform ZnO nanowires by orders of magnitude compared to surrounding PU and PDMS,
      in agreement with our experiment. It is shown that the backfilled PDMS plays a
      crucial role for the stress concentration, which leads to an efficient
      electricity generation. 

PMID- 26288273
TI  - Explorative Analysis of Wuhan Intra-Urban Human Mobility Using Social Media Check
      In Data.
AB  - Social media check-in data as a geo-tagged information source have been used for
      revealing spatio-temporal patterns in the field of social and urban study, such
      as human behavior or public issues. This paper investigates a case study and
      presents a new method of representing the mobility of people within a city from
      check-in data. By dividing the data in a temporal sequence, this study examines
      the overall mobility in the case study city through the gradient/difference of
      population density with a series of time after computing the population density
      from the check-in data using an incorporated Thiessen polygon method. By
      classifying check-in data with their geo-tags into several groups according to
      travel purposes, and partitioning the data according to administrative district
      boundaries, various moving patterns for those travel purposes in those
      administrative districts are identified by scrutinizing a series of spatial
      geometries of a weighted standard deviational ellipse (WSDE). Through deep
      analyses of those data by the adopted approaches, the general pattern of mobility
      in the case city, such as people moving to the central urban area from the suburb
      from 4 am to 8 am, is ascertained, and different characteristics of movement in
      those districts are also depicted. Furthermore, it can tell that in which
      district less movement is likely for a certain purpose (e.g., for dinner or
      entertainment). This study has demonstrated the availability of the proposed
      methodology and check-in data for investigating intra-urban human mobility. 

PMID- 26288274
TI  - Cost-Effective Control of Infectious Disease Outbreaks Accounting for Societal
      Reaction.
AB  - BACKGROUND: Studies of cost-effective disease prevention have typically focused
      on the tradeoff between the cost of disease transmission and the cost of applying
      control measures. We present a novel approach that also accounts for the cost of
      social disruptions resulting from the spread of disease. These disruptions, which
      we call social response, can include heightened anxiety, strain on healthcare
      infrastructure, economic losses, or violence. METHODOLOGY: The spread of disease
      and social response are simulated under several different intervention
      strategies. The modeled social response depends upon the perceived risk of the
      disease, the extent of disease spread, and the media involvement. Using Monte
      Carlo simulation, we estimate the total number of infections and total social
      response for each strategy. We then identify the strategy that minimizes the
      expected total cost of the disease, which includes the cost of the disease
      itself, the cost of control measures, and the cost of social response.
      CONCLUSIONS: The model-based simulations suggest that the least-cost disease
      control strategy depends upon the perceived risk of the disease, as well as media
      intervention. The most cost-effective solution for diseases with low perceived
      risk was to implement moderate control measures. For diseases with higher
      perceived severity, such as SARS or Ebola, the most cost-effective strategy
      shifted toward intervening earlier in the outbreak, with greater resources. When
      intervention elicited increased media involvement, it remained important to
      control high severity diseases quickly. For moderate severity diseases, however,
      it became most cost-effective to implement no intervention and allow the disease
      to run its course. Our simulation results imply that, when diseases are perceived
      as severe, the costs of social response have a significant influence on selecting
      the most cost-effective strategy.

PMID- 26288275
TI  - Correction: Characterization of the Kallikrein-Kinin System Post Chemical
      Neuronal Injury: An In Vitro Biochemical and Neuroproteomics Assessment.

PMID- 26288276
TI  - Effect of Intracuff Lidocaine on Postoperative Sore Throat and the Emergence
      Phenomenon: A Systematic Review and Meta-Analysis of Randomized Controlled
      Trials.
AB  - BACKGROUND: Postoperative sore throat and other airway morbidities are common and
      troublesome after endotracheal tube intubation general anesthesia (ETGA). We
      propose lidocaine as endotracheal tube (ETT) cuff inflation media to reduce the
      postintubation-related emergence phenomenon. METHODS: We searched PubMed, EMBASE,
      and Cochrane databases systematically for randomized controlled trials (RCTs)
      that have investigated the outcome of intracuff lidocaine versus air or saline in
      patients receiving ETGA. Using a random-effects model, we conducted a meta
      analysis to assess the relative risks (RRs) and mean difference (MD) of the
      incidence and intensity of relevant adverse outcomes. RESULTS: We reviewed
      nineteen trials, which comprised 1566 patients. The incidence of early- and late
      phase postoperative sore throat (POST), coughing, agitation, hoarseness, and
      dysphonia decreased significantly in lidocaine groups, with RRs of 0.46 (95%
      confidence interval [CI]: 0.31 to 0.68), 0.41 (95% CI: 0.25 to 0.66), 0.43 (95%
      CI: 0.31 to 0.62), 0.37 (95% CI: 0.25 to 0.55), 0.43 (95% CI: 0.29 to 0.63), and
      0.19 (95% CI: 0.08 to 0.5), respectively, when compared with the control groups.
      The severity of POST also reduced significantly (mean difference [MD] -16.43 mm,
      95% CI: -21.48 to -11.38) at 1 h and (MD -10.22 mm, 95% CI: -13.5 to -6.94) at 24
      h. Both alkalinized and non-alkalinized lidocaine in the subgroup analyses showed
      significant benefits in emergence phenomena prevention compared with the control.
      CONCLUSION: Our results indicate that both alkalinized and non-alkalinized
      intracuff lidocaine may prevent and alleviate POST and postintubation-related
      emergence phenomena.

PMID- 26288277
TI  - Low Level Engraftment and Improvement following a Single Colonoscopic
      Administration of Fecal Microbiota to Patients with Ulcerative Colitis.
AB  - OBJECTIVE: Fecal microbiota transplantation (FMT) is an investigational treatment
      for diseases thought to involve alterations in the intestinal microbiota
      including ulcerative colitis (UC). Case reports have described therapeutic
      benefit of FMT in patients with UC, possibly due to changes in the microbiota. We
      measured the degree to which the transplanted microbiota engraft following FMT in
      patients with UC using a donor similarity index (DSI). METHODS: Seven patients
      with mild to moderate UC (UC disease activity index scores 3-10) received a
      single colonoscopic administration of FMT. Metagenomic sequence data from stool
      were analyzed using an alignment-free comparison tool, to measure the DSI, and a
      phylogenetic analysis tool, to characterize taxonomic changes. Clinical,
      endoscopic, histologic, and fecal calprotectin outcome measures were also
      collected. RESULTS: One of 5 patients from whom sequencing data were available
      achieved the primary endpoint of 50% donor similarity at week 4; an additional 2
      patients achieved 40% donor similarity. One patient with 40% donor similarity
      achieved clinical and histologic remission 1 month after FMT. However, these were
      lost by 2-3 months, and loss correlated with a decrease in DSI. The remaining
      patients did not demonstrate clinical response or remission. Histology scores
      improved in all but 1 patient. No patients remained in remission at 3 months
      after FMT. CONCLUSIONS: Following a single colonoscopic fecal transplant, a DSI
      of 40-50% is achieved in about two-thirds of recipients. This level of
      engraftment correlated with a temporary clinical improvement in only 1/5
      patients. Larger sample sizes could further validate this method for measuring
      engraftment, and changes in transplant frequency or method might improve
      microbiota engraftment and efficacy. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT01742754.

PMID- 26288278
TI  - Movement prediction using accelerometers in a human population.
AB  - We introduce statistical methods for predicting the types of human activity at
      sub-second resolution using triaxial accelerometry data. The major innovation is
      that we use labeled activity data from some subjects to predict the activity
      labels of other subjects. To achieve this, we normalize the data across subjects
      by matching the standing up and lying down portions of triaxial accelerometry
      data. This is necessary to account for differences between the variability in the
      position of the device relative to gravity, which are induced by body shape and
      size as well as by the ambiguous definition of device placement. We also
      normalize the data at the device level to ensure that the magnitude of the signal
      at rest is similar across devices. After normalization we use overlapping
      movelets (segments of triaxial accelerometry time series) extracted from some of
      the subjects to predict the movement type of the other subjects. The problem was
      motivated by and is applied to a laboratory study of 20 older participants who
      performed different activities while wearing accelerometers at the hip.
      Prediction results based on other people's labeled dictionaries of activity
      performed almost as well as those obtained using their own labeled dictionaries.
      These findings indicate that prediction of activity types for data collected
      during natural activities of daily living may actually be possible.

PMID- 26288279
TI  - The Effects of All-Trans Retinoic Acid on the Induction of Oral Tolerance in a
      Murine Model of Bronchial Asthma.
AB  - BACKGROUND: Active suppression induced by regulatory T (Treg) cells is reported
      to be one of the mechanisms involved in oral tolerance. All-trans retinoic acid
      (ATRA) has been reported to affect Treg cell differentiation. The present study
      examined the effects of ATRA on the induction of oral tolerance in a murine model
      of bronchial asthma. METHODS: BALB/c mice were sensitized to and challenged with
      ovalbumin (OVA) through feeding followed by OVA challenges. In some study groups
      ATRA was orally administered concomitantly with OVA feeding either in the
      presence or absence of the retinoic acid receptor antagonist LE135. Lung CD4+ T
      cells were isolated from mice exposed to ATRA and/or OVA, and transferred to
      control mice. Airway hyperresponsiveness (AHR), cell counts and cytokine levels
      in bronchoalveolar lavage (BAL) fluid, and lung histology were assessed. RESULTS:
      Concomitant administration of ATRA with OVA ameliorated AHR, airway eosinophilia,
      elevation of cytokines in BAL fluid and goblet cell metaplasia. The proportion of
      Treg cells in the lungs was increased in mice treated with OVA and ATRA, as
      compared to those treated with OVA only. Transfer of lung CD4+ T cells from mice
      treated with OVA and ATRA induced suppression of AHR and airway inflammation.
      LE135 completely reversed the effects of ATRA on AHR, airway allergic
      inflammation and the number of Treg cells in the lungs. CONCLUSION: These data
      suggested that oral administration of ATRA with OVA had the potential to enhance
      oral tolerance in this murine model of bronchial asthma. These effects were
      mediated, at least in part, by Treg cell expansion.

PMID- 26288280
TI  - [Photosensitivity, epilepsy, the occipital and frontal cortex].
AB  - This article discusses the features of the structural-functional organization of
      the visual distance perception which, in contrast to other distant sensory
      systems, has not only afferent but also efferent part--the frontal visual field
      and, smooth and stripy muscles of the eye which accordingly support the visual
      function. The increasing importance of the efferent component of the visual
      system in the present conditions of real and virtual movements of visual objects
      is shown. The case of photosensitivity in epilepsy proves the fact that the
      efferent component of the visual system can react in a protective way to the
      rhythmic photostimulation.

PMID- 26288281
TI  - [Clinical/encephalographic syndrome of dopamine deficiency in patients with
      depressed consciousness after severe brain injury].
AB  - OBJECTIVE: To determine electroencephalographic signs of dopamine deficiency
      syndrome during the recovery after severe brain injury (SBI). MATERIAL AND
      METHODS: We studied 35 patients with SBI (23 men and 12 women, mean age 29 +/- 13
      years). RESULTS AND CONCLUSION: We identified a set of neurological symptoms
      (increased muscular tone of extrapyramidal type, rest tremor, autonomic
      disorders, which were most characteristic of the autonomic state, and some forms
      of mutism associated, according to current conceptions, with the dopaminergic
      system deficiency syndrome. This clinical picture was accompanied by stable EEG
      changes: an increase in the severity of beta activity of 13-14 Hz, enhanced in
      the frontal and anterior temporal areas, synchronized with equivalent dipole
      source localization in subcortical and frontal/basal areas. Dopamine deficiency
      regression syndrome was accompanied by an increase in beta EEG activity (from 13
      to 16 Hz), but with the persistent abnormal enhancement of coherent hemispheric
      relations, especially in the occipital-temporal areas.

PMID- 26288282
TI  - [Borderline mental disorders in schoolchildren].
AB  - OBJECTIVE: To study the frequency of borderline mental disorders in children of
      secondary general education schools. MATERIAL AND METHODS: We examined 1013 male
      and female schoolchildren, aged 12-14 and 15-17 years. In the first stage, the
      they completed a screening questionnaire to estimate the presence of a range of
      psychosomatic syndromes. An analysis of medical history and clinical examination
      were performed as well. The second stage included medical examination using DAWBA
      for the children with total scores on The Strengths and Difficulty questionnaire
      >= 16; with the score >= 6 on the emotional scale and with the score <= 5 on the
      social scale. RESULTS AND CONCLUSION: Generalized anxiety and depression were
      recorded more often in girls than in boys. Every 4-th adolescent (26.1%),
      regardless of gender, had problems in communication with peers. At the same time,
      boys showed conduct disturbances more often (p = 0.005) than girls (23.3% and
      16.3%, respectively). Depression syndrome was 6.1 times more frequent in
      adolescents of the older group as compared with younger children (p = 0.024).
      Depression was associated with chronic headache (68.6% of children, mostly in
      girls and in the older group), abdominal pain (37.3%, mostly in girls) and back
      pain (39.2%).

PMID- 26288283
TI  - [Cognitive impairments in persons exposed to radiation during the period of
      prenatal development].
AB  - OBJECTIVE: To assess the cognitive status in persons exposed to ionizing
      radiation in prenatal period. MATERIAL AND METHODS: The study included in-utero
      exposed people (n = 77), and the comparison group (n = 73), which consisted of
      people who lived in the territories of the Chelyabinsk Oblast that were not
      radioactive. The following methods were used: clinical, clinical-psychological
      (Mini-Mental State Examination (MMSE), the WAIS test, the proverb interpretation
      task, neurophysiological (EEG) methods, laboratory-based methods (cholesterol,
      high and low-density lipoproteins, triglycerides, cortisol, melatonin), and
      methods of statistical data processing. RESULTS AND CONCLUSION: The number of
      people with non-psychotic mental disorders with the prevalence of organic mental
      disorders (cognitive and asthenic) was significantly higher among in-utero
      exposed subjects. A neurophysiological study revealed more severe changes in the
      bioelectric brain activity with the presence of pathological and theta-rhythms in
      exposed persons. The clinical-psychological study revealed a significant decrease
      in the analytic/synthetic ability in exposed people and significantly lower level
      of the general and verbal IQ. These changes were accompanied by higher levels of
      cortisol and melatonin which led to the activation and tension of the adaptation
      mechanisms in in-utero exposed subjects.

PMID- 26288284
TI  - [Acute symptomatic epileptic seizures and status epilepticus].
AB  - Acute symptomatic seizures (ASS) are the seizures of different etiology that
      occur in close temporary relationship to acute damage of the central nervous
      system arising simultaneously due to metabolic, toxic, infectious and
      inflammatory factors and structural brain damage. At the time of its origin, ASS
      is often not distinguished from epileptic seizures in the clinical and
      electrophysiological parameters, although represent a fundamentally different
      state from the point of view of pathogenesis, therapy and prognosis. Tactics in
      the ASS and symptomatic epileptic status of any nature provides for the immediate
      carrying out differential diagnosis and differential treatment. Treatment of ASS
      includes two aspects: reduction in ictal activity (seizures) and prevention of
      future development of seizures through the elimination or correction of
      physiological trigger of the attacks and the decision to conduct a long-term
      antiepileptic drug therapy if the risk of seizures is saved.

PMID- 26288285
TI  - [A role of melatonin in the treatment of low back pain].
AB  - OBJECTIVE: To study an analgesic role of melatonin in the treatment of low back
      pain. MATERIAL AND METHODS: A study included 178 patients, aged from 40 to 65
      years, with low back pain during at least 12 weeks and the VAS score > 3.
      Patients were stratified into 6 groups (3 pairs of comparison). In the first
      pair, patients of the main group (n = 31) received APTPA (a combination of 500 mg
      of glucosamine hydrochloride and 500 mg of chondroitin sulfate) in dosage 1
      tablet twice a day during 1 month and then 1 tablet during 2 months plus melaxen
      (3 mg of melatonin 30-40 min before sleep), patients of the control group (n =
      29) received only APTPA. In the second pair, patients of the comparison group (n
      = 30) received APTPA in dosage 1 tablet twice a day and diclofenac in dosage 25
      mg 2-3 times a day, patients of the main group (n = 30) received additionally
      melaxen (3 mg of melatonin 30-40 min before sleep). In the third pair, patients
      of the main group (n = 29) received APTPA in dosage 1 tablet twice a day,
      diclofenac in dosage 25 mg 2-3 times a day and melaxen (3 mg of melatonin 30-40
      min before sleep), patients of the comparison group (n = 29) did not receive
      melaxen. Treatment results were assessed after 3 months for the first pair and
      after 1 month for the second and third pairs. RESULTS: A significant reduction in
      pain intensity at movement and resting state was noted in the main groups
      compared to controls. CONCLUSION: Possible mechanisms of analgesic properties of
      melatonin and world experience in chronic low back pain treatment are discussed.

PMID- 26288286
TI  - [Algorithms of using valproic acid drugs in women].
AB  - Characteristics of using valproic acid drugs in women, from puberty to menopause
      period, are reviewed. Based on initial treatment efficacy, type of epileptic
      seizures and a form of epilepsy, the author emphasizes the practical use of
      valproates during pregnancy in dependence on the situation. Several scenarios of
      pregnancy course and possible treatment tactics are presented.

PMID- 26288287
TI  - [The results of single-event multilevel orthopedic surgeries and the early
      rehabilitation used in complex with botulinum toxin treatment in patients with
      spastic forms of cerebral palsy].
AB  - OBJECTIVE: To evaluate motor possibilities of patients with children spastic
      palsy (CSP) one year after single-event multilevel orthopedic low extremity
      surgeries in combination with early rehabilitation treatment including botulinum
      toxin treatment. MATERIAL AND METHODS: Authors studied the results of operative
      orthopedic treatment in 55 patients with CSP, aged from 5 to 17 years (mean 11.9
      +/- 2.5 years), who underwent multilevel surgeries with early functional
      rehabilitation using 1.5 treatment courses with 6-8 week treatment-free periods
      during 9-12 months in combination with a single injection of disport in the post
      operative period. We performed 74 surgeries 140 episodes of botulinum toxin
      treatment using average doses of Botulinum toxin 10 U per kg of body mass
      injected into low extremity muscles. RESULTS: In the post-operative period,
      authors recorded a significant reduction in pain syndrome, assessed with a pain
      intensity scale, from 8.6 +/- 1.2 to 4.3 +/- 1.1 scores (p < 0.001). An analysis
      of gait demonstrated an improvement of gait patterns in all patients able to move
      independently. An increase in motor abilities, measured with the Gillette
      Functional Assessment Questionnaire, by 1 level was identified in 28 (50.9%)
      patients, by 2 levels in 2 (3.6%) patients, no changes were observed in 25
      (45.5%) patients. CONCLUSION: Single-event multilevel orthopedic surgeries in
      children with CSP reduce a number of repeated surgeries. The effective control
      over pain syndrome in patients with CSP using multilevel botulinum toxin
      treatment in the post-operative period promotes the functional rehabilitation,
      increases rates of loading during training sessions and the motivation of CSP
      patients to restore the lost activity.

PMID- 26288288
TI  - [Clinical and immunological correlations in endogenous depression].
AB  - OBJECTIVE: To study the possibility of using immunological parameters for the
      evaluation of the activity of endogenous process in depression and quality of
      response to psychopharmacotherapy. MATERIAL AND METHODS: Authors examined 42
      patients, aged 20-55 years, with the prevalence of anxiety (n = 22) or apathy (n
      = 20) in the clinical picture of depression. The following immunological
      parameters were measured in the blood of the patients: degranulation activity of
      leukocyte elastase (LE), functional activity of alpha-1-proteinase inhibitor
      (alpha-1-PI); the level of autoantibodies to neuroantigen S-100B and myelin basic
      protein. RESULTS AND CONCLUSION: The involvement of inflammatory and autoimmune
      responses in the pathophysiology of endogenous depression was confirmed.
      Depression associated with increased levels of autoantibodies to brain
      neuroantigens (an autoimmune component) had a more complicated structure and
      showed the tendency to prolonged course and resistance to the therapy. The
      results suggest that some immunological parameters may be used as markers of
      patient's clinical status and quality and completeness of psychopathological
      symptom reduction.

PMID- 26288289
TI  - [The evaluation of hyperkineses in hepatocerebral dystrophy (Wilson-Konovalov
      disease) from the position of the theory of muscle spindles].
AB  - OBJECTIVE: To obtain evidence for the possibility of considering hyperkineses in
      hepatocerebtal dystrophy from the position of the theory of muscle spindles.
      MATERIAL AND METHODS: We examined 27 patients: rigid-arrhythmic-hyperkinetic form
      was diagnosed in 2 patients, trembling-rigid in 8, trembling in 16 and
      extrapyramidal-cortical in 1. Electromyography of different muscles in resting
      state and functional loadings taking into account surgical intervention was the
      main method of the study. RESULTS AND CONCLUSION: An analysis of
      electrophysiological results based on hyperkinesis variant (torsion dystonic,
      choreoathetoid etc) revealed a role of the striatal pallidal system in the
      anomalous control of static and dynamic gamma-motorneurons and involvement of
      spinal reflexes in forced movements. This hypothesis may help to deeply
      understand the genesis of extrapyramidal dyskinesia and more reasonably select a
      stereotaxic target in surgical treatment.

PMID- 26288290
TI  - [Morphometric features of the structure of the central nucleus of the amygdala in
      men and women].
AB  - OBJECTIVE: To identify the interhemispheric asymmetry in the structure of the
      central nucleus of the amygdala in men and women. MATERIAL AND METHODS:
      Morphometric features of the structure of neurons of the central nucleus amygdala
      complex were studied in histological sections of the brain of 6 men and 6 women
      (24 hemispheres), aged 19 to 55 years, with no lifetime diagnosis of mental or
      neurological disease. The value of the profile fields of neurons of the central
      nucleus amygdala complex in the left and right hemispheres of the brain were
      investigated. RESULTS AND CONCLUSION: In women, the average value of neurons in
      the left hemisphere was somewhat greater than in the right hemisphere, while in
      men this value was greater in the right hemisphere. The interhemispheric
      morphometric differences were not significant regardless of gender. In addition,
      the quantity of relevant fields of neurons in the central nucleus of the amygdala
      in women was significantly larger than that of men in both hemispheres. The
      authors attempted to associate the results obtained in the study with emotional
      perception in men and women.

PMID- 26288291
TI  - [Clinical/dynamic and epidemiological aspects of depressive disorders in the
      protracted emergency situation].
AB  - OBJECTIVE: Depressive disorders are one of the most frequent forms of mental
      pathology developed in protracted emergency situations. Depression develops
      independently or comorbid to posttraumatic stress disorder (PTSD). MATERIAL AND
      METHODS: Authors conducted a population study of the dynamics of depressive
      disorders in people lived in the area of combat actions in the Chechen Republic.
      The study included 1000 patients. It started in 2002 with a follow up period of 2
      years (2004, 2006 and 2008). RESULTS AND CONCLUSION: Affective disorders of
      different severity were identified in 40% of the sample. The percentage of
      depressive disorders decreased with time since the acute phase of the emergency
      situation, though after 6 years remained significantly higher than in the control
      area without combat exposure. The issues of providing care to patients with
      affective disorders are considered.

PMID- 26288292
TI  - [Clinical guidelines "Rational use of nonsteroidal anti-inflammatory drugs
      (NSAIDs) in clinical practice". Part I].

PMID- 26288293
TI  - [The use of buspirone in clinical practice].
AB  - Buspirone, a nonbenzodiasepine anxiolytic, is a partial serotonin 5-HT1A-receptor
      agonist, D2-autoreceptor antagonist and low affinity 5-HT2-receptor agonist. This
      medication is used for treatment of generalized anxiety disorder though it may be
      prescribed in other anxiety states, primarily, panic disorder, sociophobia and
      depression. Buspirone seems to be potential in treatment of other neurological
      and mental disorders (tardive dyskinesia in Parkinson's disease, ataxia,
      behavioral disorders, cranial/brain injuries, dementia, attention-deficit
      hyperactivity disorder).

PMID- 26288294
TI  - [Pathological fear of weight gain is a necessary criterion of anorexia nervosa].
AB  - OBJECTIVE: To analyze the diagnostic value of fear of weight gain (obesity)
      criterion in anorexia nervosa (AN). MATERIAL AND METHODS: Authors examined 30
      patients with significant weight loss due to self-restriction of food intake. The
      patients were stratified into the group (n = 15) that met ICD-10 criteria of AN
      (restrictive variant) and the group with somatoform dysfunction of the autonomic
      nervous system of the gastrointestinal tract. Authors compared these groups and
      presented a description of two cases. RESULTS: The patients of the second group
      met 3 of 4 AN criteria and would be formally diagnosed with atypical AN but they
      had not the fear of weight gain. Moreover, the patients of this group
      significantly differed by several clinical parameters and responses to treatment.
      In diagnostic view, the most important is the presence of the
      dysmorphophobia/dysmorphomania syndrome in patients with AN and hypochondriac
      syndrome in the patients with somatoform dysfunction. CONCLUSION: The diagnostic
      criteria of eating disorders should be revised. However, "fear of weight gain",
      to our opinion, should be considered as a necessary criterion of AN.

PMID- 26288295
TI  - [A new method of treatment of Korsakoff's (amnestic) psychosis: neurostimulation
      correction of the sympathetic nervous system].
AB  - AIM: To provide a rationale for a new method of neurostimulation - correction of
      the sympathetic nervous system based on the evolution of the electrical
      stimulation of the brain as a component of neurorehabilitation. MATERIAL AND
      METHODS: Authors treated 16 patients with Korsakoff's (amnestic) psychosis using
      this method. RESULTS: Positive results were obtained in all patients. A typical
      case is described. CONCLUSION: The proposed method has a high therapeutic
      potential.

PMID- 26288296
TI  - [Laboratory predictors of delirium tremens severity].
AB  - AIM: To identify the most informative predictors of delirium tremens severity.
      MATERIAL AND METHODS: A total of 105 patients from a department of urgent drug
      addiction help of the Chelyabinsk regional addiction hospital were examined. To
      find the most informative predictors of delirium tremens severity, we studied a
      relationship between biogenic amine metabolism and changes in cortisol levels in
      dependence of patients' condition. The level of catecholamines (adrenaline,
      noradrenaline, dopamine) and their precursor 3'4-dioxyphenylalanine in blood and
      daily urine, serotonin and histamine content, thrombocyte monoamine oxidase B
      activity, urinary tribulin activity, and serum cortisol levels of the patients
      with different severity of delirium tremens were assessed. RESULTS AND
      CONCLUSION: A prognostic significance of cortisol and blood serotonin levels, and
      thrombocyte monoamine oxidase activity was demonstrated. A decrease in cortisol
      levels was the most negative predictor.

PMID- 26288297
TI  - [Stabilization of remission in patients with opioid dependence with naltrexone
      implant: a pharmacogenetic approach].
AB  - AIM: To evaluate the effect of opioid receptor genes and dopamine system genes
      polymorphisms on treatment outcomes of opioid dependence with implantable and
      oral naltrexone. MATERIAL AND METHODS: Authors carried out a randomized double
      blind, double-dummy, placebo-controlled clinical trial. Three hundred and six
      patients with opioid dependence were randomized into 3 equal treatment groups.
      The first group received implantation of 1000 mg naltrexone every 2 months during
      6 months + oral naltrexone placebo; the second group - placebo implant every 2
      months + oral naltrexone (50mg/day) and the third group - placebo implant + oral
      naltrexone placebo. It was genotyped polymorphisms in the following genes: mu
      opioid receptor (OPRM1), kappa-opioid receptor (OPRK1), catechol-O
      methyltransferase (COMT), dopamine receptors types 2 (DRD2) and 4 (DRD4),
      dopamine-beta-hydroxylase, and dopamine transporter (DAT1). RESULTS: Regardless
      of treatment several polymorphisms of these genes were associated with high risk
      of relapse: an allele L (2R) DRD4 120bp (p=0.05; OR (95% CI)=3.3(1.1-10.1)); an
      allele S DRD2 NcoI (r=0,051; OR (95% CI)=2,86 (1,09-7,52)); the genotype 9.9 DAT
      VNTR 40bp (r=0,04; OR (95% CI)=1,4 (1,3-1,5)); on the contrary, (SS+ST)-(TT))
      variants of OPRK1-DRD2Ncol increased a chance to complete treatment program
      (r=0,004; OR (95% CI)=7.4 (1.8-30.4)), Kaplan-Meier survival analysis (r=0,016).
      The probability of completing treatment program by the carriers of these variants
      was higher in the oral naltrexone group (p=0.016), lower in the double placebo
      group (p=0.015), but did not influence on treatment outcomes in the naltrexone
      implant group. CONCLUSION: Naltrexone-implant is a highly effective medication
      for treatment of opioid dependence and its effectiveness exceeds that of oral
      naltrexone and placebo. The study has shown the joint influence of opioid
      receptor genes and genes of dopaminergic system on treatment outcomes of opioid
      dependence. Genetic analysis is useful for determining potential responders to
      naltrexone treatment of opioid dependence.

PMID- 26288298
TI  - [Long-term results of the program "Point of Sobriety" in patients with alcohol
      dependence in the Krasnodar region].
AB  - AIM: To analyze the long-term results of the "Point of Sobriety" program in
      patients with alcohol dependence. MATERIAL AND METHODS: It was analyzed the
      results of treatment of 104 patients treated 2 or more years before the current
      study. RESULTS AND CONCLUSION: The high efficacy of complex treatment with
      naltrexone injections was demonstrated. Remission during more than 1 year was
      achieved in 64.4% of patients, more than 2 years in 45.2%. Most patients reported
      improvement in social and family status.

PMID- 26288299
TI  - [Pychotherapy in patients with alcohol dependence and comorbid endogenous
      pathology].
AB  - AIM: To develop differential psychotherapeutic methods in the combined treatment
      of patients with alcohol dependence and comorbid paranoid schizophrenia. MATERIAL
      AND METHODS: Authors treated 154 patients using a specially designed
      psychotherapeutic program. The sample was randomized into the experimental and
      control groups. The experimental group received the psychotherapeutic program in
      contrast to the control group. RESULTS: The psychotherapeutic program based on
      the treatment of alcohol-dependence symptoms and patterns of coping with mental
      disorder symptoms was effective for the patients. Participation in the program
      allowed patients with alcohol dependence and comorbid schizophrenia to reduce
      manifestations of pathological craving for alcohol. CONCLUSION: The appropriate
      psychopharmacotherapy of endogenous disorder symptoms is an essential condition
      for successful psychotherapy, especially at the beginning of the treatment.

PMID- 26288300
TI  - [Sleep disorders in alcoholism].
AB  - This is a review of the literature on inhibitory effects of alcohol on activating
      systems and stimulation of synchronizing systems in the CNS. Inhibitory effects
      were seen as a sedation in the first half of night and worsening in the process
      of ethanol metabolism. Alcohol withdrawal after a long period of alcohol abuse
      often causes severe insomnia. Tolerance to hypnotic effect of alcohol as well as
      addiction and abuse are frequent in patients with insomnia who use it as sleeping
      aid. Correction of insomnia in alcoholics involves anticonvulsants and
      antidepressants in combination with cognitive-behavior therapy. 

PMID- 26288301
TI  - [A clinical and psychological study of tobacco dependence in patients with
      alcoholism].
AB  - AIM: To study the effect of sex- and age-related features, social aspects and
      progression of alcoholism on tobacco smoking (TS), tobacco dependence (TD) and
      alcohol dependence (AD) in the Chuvash Republic. MATERIAL AND METHODS: Authors
      questioned 769 inpatients with AD and then performed detailed examination and
      questioning of 390 patients. RESULTS AND CONCLUSION: 74.4% patients with AD
      (82.2% men and 41.6% women) were cigarette smokers. According to the Fagerstrom's
      test, 79.2% had Nicotine Dependence (ND), 80.3% smoked more than 10 cigarettes
      per day. ND was diagnosed much more often in men, TS in them was more intense in
      comparison with women. There were highly significant correlations between
      alcoholism progression and TS or TD. Patients with AD had more significant ND
      compared to total population. They started TS much earlier, more often didn't
      prefer a particular brand of cigarettes, smoked high pitch cigarettes.
      Rejuvenation of TS onset with the fast formation of ND and AD is noted.

PMID- 26288302
TI  - [The use of melatonin in narcological practice].

PMID- 26288303
TI  - [Duration of therapeutic remission alcohol dependence: a role of dopamine system
      genes polymorphism and family history density].
AB  - AIM: A quantitative assessment of the impact of genetic factors (density of
      family history of alcohol dependence and dopamine system genes polymorphisms) on
      the average time to relapse (ATR) after alcohol dependence treatment (duration of
      therapeutic remission from alcohol dependence). MATERIAL AND METHODS: Authors
      studied 247 male Russian inpatients diagnosed with ICD-10 F10.2 who had at least
      two therapeutic remissions before the current hospitalization and 259 healthy
      controls. ATR and the density of family history of alcohol dependence were
      evaluated retrospectively according to the clinical interview. RESULTS AND
      CONCLUSION: The high density of family history (at least 2 people with alcohol
      problems among the blood relatives) and some dopamine system genes polymorphisms
      significantly affect the average time to relapse. An allele A9 of the dopamine
      transporter gene (DAT VNTR 40 bp) was associated (p=0.003; OR=1.73) with short
      (up to 12 months) average time to relapse. A trend toward association (p=0.052)
      was noted for dopamine receptor type 2 gene polymorphisms (rs1800497, rs6275).
      Patients with long-term ATR are genetically different from patients with short
      ATR by the set of variants of tyrosine hydroxylase gene (HUMTH01, p=0.002;
      OR=3.08) and from the control group by the genotype LH of the catechol-O
      methyltransferase gene (rs4680, p=0.02; OR=2.33). Some other sets of HUMTH01
      variants (p=0.0001; OR=2.38) and the dopamine receptor type 4 (DRD4 VNTR 48 bp,
      p=0.055) may have protective properties with regard to short ATR. Polymorphisms
      (rs1108580, rs1611115) of the dopamine-beta-hydroxylase gene were not related to
      the ATR.

PMID- 26288304
TI  - [Accuracy of the choice of the dependence syndrome treatment: evidence-based
      addictology against clinical practice].
AB  - In article it is analyzed the reasons of discrepancy of arguments at a choice of
      dependence syndrome treatment in Russian, in particular when forming National
      clinical protocols. The conclusion that rejection of use principles of evidence
      based medicine is based on the objective and subjective reasons is drawn. Lack of
      available Russian-speaking scientific literature, insufficient level of knowledge
      of English for acquaintance with bases of Cochrain library and scientific
      articles concerns to the first. To the second - domination of the concept "a
      pathological craving", considering an criving as a psychotic syndrome (delusion)
      and use antipsychotics for its treatment. 

PMID- 26288305
TI  - [Metabolic disturbances and ways of their pharmacological correction in acute
      poisoning with ethanol in patients with chronic alcoholism].
AB  - AIM: To study an influence of chronic alcoholism on the clinical course and
      severity of metabolic disturbances in patients with acute poisoning with ethanol
      and to improve the treatment. MATERIAL AND METHODS: Authors examined 93 patients
      stratified into three groups (acute poisoning with ethanol in patients with
      chronic alcoholism, without chronic alcoholism and those treated with reamberin).
      RESULTS AND CONCLUSION: The presence of chronic alcoholism significantly
      augmented metabolic disturbances and influenced the disturbance of oxygen
      transport function and free-radical processes in patients with acute intoxication
      with ethanol. Using of reamberin in the complex intensive therapy led to the
      decrease in metabolic disorders, which improved the clinical course of acute
      poisoning with ethanol in patients with chronic alcoholism.

PMID- 26288306
TI  - [The correlation between the levels of cortisol and free radical oxidation in
      patients with heroin addiction depending on gender differences].
AB  - AIM: To evaluate gender effects on the correlation between cortisol, molecular
      products of lipid peroxidation (LPO) and carbonylation of proteins in patients
      with heroin addiction. MATERIAL AND METHODS: Authors examined 82 patients, 49 men
      and 33 women, with heroin addiction. Biochemical and statistical methods were
      used. RESULTS AND CONCLUSION: Gender differences in the carbonylation of proteins
      were noted. In men, but not in women, the low level of cortisol was associated
      with an increased content of carbonylated proteins. In women the level of these
      proteins was lower than in men. Gender did not exert an effect on LPO.

PMID- 26288307
TI  - [Morphine-induced Straub tail reaction as a model of spasticity in mice: effects
      of serotonergic compounds].
AB  - AIM: To adopt and validate the Straub tail reaction (SR) for comparative
      assessment of spastic effects of serotonergic compounds. MATERIAL AND METHODS: To
      measure the muscle relaxant activity, the morphine-induced Straub-tail assay was
      used. SR was graded according to modified intensity-score basis in a scale
      decribed by Kameyama et al. (1978). Subcutaneous injections of different doses of
      morphine (10-60 mg/kg) induced a dose-dependent SR with maximum response obtained
      15-30 min after the morphine administration. RESULTS AND CONCLUSION: The
      centrally acting muscle relaxant baclofen (3-10 mg/kg) reduced SR induced by
      morphine (40 mg/kg) at all used doses; tizanidine decreased the intensity of SR
      at highest doses tested (0.6 and 1 mg/kg). Dantrolene (20-100 mg/kg), a
      peripherally acting muscle relaxant, did not affect SR. Effects of serotonergic
      agents depended on the specific mechanism of action. SR appears to be available
      for rapid evaluation of the effect of antispasticity drugs.

PMID- 26288308
TI  - [Syndrome of emotional burnout in narcologists and its impact on quality of life
      of patients with alcohol dependence].
AB  - AIM: To determine the frequency of syndrome of emotional burnout (SEB) and
      severity of its stages in addiction psychiatrists and to evaluate quality of life
      of their inpatient and outpatient narcologist. MATERIAL AND METHODS: Authors
      examined 107 narcologist using a method of V.V. Boyko. Of those diagnosed with
      SEB, we examined the groups of their patients with alcohol dependence (10
      patients in each group). It was evaluated quality of life of the patient and its
      changes with regard to the stage and severity of SEB in the psychiatrist. RESULTS
      AND CONCLUSION: Symptoms of SEB were identified in most of addiction
      psychiatrists. The severity of SEB was more marked in psychiatrists of outpatient
      practice compared to those of inpatient practice. The burnout phase "exhaustion"
      developed in 31.5% of the addiction psychiatrists of outpatient practice. The
      negative impact of SEB in the psychiatrist on the quality of life of the
      outpatient with alcohol dependence was shown.

PMID- 26288309
TI  - Independent Tuning of Electronic Properties and Induced Ferromagnetism in
      Topological Insulators with Heterostructure Approach.
AB  - The quantum anomalous Hall effect (QAHE) has been recently demonstrated in Cr-
      and V-doped three-dimensional topological insulators (TIs) at temperatures below
      100 mK. In those materials, the spins of unfilled d-electrons in the transition
      metal dopants are exchange coupled to develop a long-range ferromagnetic order,
      which is essential for realizing QAHE. However, the addition of random dopants
      does not only introduce excess charge carriers that require readjusting the Bi/Sb
      ratio, but also unavoidably introduces paramagnetic spins that can adversely
      affect the chiral edge transport in QAHE. In this work, we show a heterostructure
      approach to independently tune the electronic and magnetic properties of the
      topological surface states in (BixSb1-x)2Te3 without resorting to random doping
      of transition metal elements. In heterostructures consisting of a thin (BixSb1
      x)2Te3 TI film and yttrium iron garnet (YIG), a high Curie temperature (~550 K)
      magnetic insulator, we find that the TI surface in contact with YIG becomes
      ferromagnetic via proximity coupling which is revealed by the anomalous Hall
      effect (AHE). The Curie temperature of the magnetized TI surface ranges from 20
      to 150 K but is uncorrelated with the Bi fraction x in (BixSb1-x)2Te3. In
      contrast, as x is varied, the AHE resistivity scales with the longitudinal
      resistivity. In this approach, we decouple the electronic properties from the
      induced ferromagnetism in TI. The independent optimization provides a pathway for
      realizing QAHE at higher temperatures, which is important for novel spintronic
      device applications. 

PMID- 26288310
TI  - Salivary secretion and drug treatment in four 70-year-old Swedish cohorts during
      a period of 30 years.
AB  - OBJECTIVE: The aim was to examine the association between drug treatment and
      unstimulated and stimulated whole saliva in four 70-year-old Swedish cohorts,
      between 1971 and 2001. BACKGROUND: Both diseases and their medication can affect
      the salivary secretion rate. MATERIALS AND METHODS: The study was based on
      selected samples of four cohorts born in 1901/1902, 1906/1907, 1911/1912 and
      1930/1931, respectively, a total of 1072 individuals. The response rate varied
      between 65% and 85%. RESULTS: The mean value for the stimulated salivary
      secretion rate was higher in men (1.3 +/- 0.8 ml/min) than in women (1.0 +/- 0.7
      ml/min) (p < 0.001)). There was a significant association between the salivary
      secretion rate and the number of drugs among both women (p < 0.01) and men (p <
      0.001). This influence was most pronounced in participants who were treated with
      cardiovascular drugs, mainly diuretics and non-selective beta-adrenoceptor
      blockers, but also with antipsychotics and antidepressants, even when adjusted
      for cohort, gender, number of teeth and other drugs. There was an increase in
      treatment with medicines during the three decades. CONCLUSION: In these four
      groups of 70-year-old participants, high drug consumption was associated with
      lower salivary flow. Unstimulated secretion was only affected in women and then,
      when taking four or more drugs. Pronounced hyposalivation was, however, uncommon.
      Cardiovascular drugs, antidepressants and antipsychotics were associated with low
      salivary secretion. In this age group, the frequently observed association
      between polypharmacy and a lower saliva secretion rate represents a risk of
      impaired dental health.

PMID- 26288311
TI  - Definition of chronic hepatitis E after liver transplant conforms to convention.

PMID- 26288312
TI  - The Pagerank-Index: Going beyond Citation Counts in Quantifying Scientific Impact
      of Researchers.
AB  - Quantifying and comparing the scientific output of researchers has become
      critical for governments, funding agencies and universities. Comparison by
      reputation and direct assessment of contributions to the field is no longer
      possible, as the number of scientists increases and traditional definitions about
      scientific fields become blurred. The h-index is often used for comparing
      scientists, but has several well-documented shortcomings. In this paper, we
      introduce a new index for measuring and comparing the publication records of
      scientists: the pagerank-index (symbolised as pi). The index uses a version of
      pagerank algorithm and the citation networks of papers in its computation, and is
      fundamentally different from the existing variants of h-index because it
      considers not only the number of citations but also the actual impact of each
      citation. We adapt two approaches to demonstrate the utility of the new index.
      Firstly, we use a simulation model of a community of authors, whereby we create
      various 'groups' of authors which are different from each other in inherent
      publication habits, to show that the pagerank-index is fairer than the existing
      indices in three distinct scenarios: (i) when authors try to 'massage' their
      index by publishing papers in low-quality outlets primarily to self-cite other
      papers (ii) when authors collaborate in large groups in order to obtain more
      authorships (iii) when authors spend most of their time in producing genuine but
      low quality publications that would massage their index. Secondly, we undertake
      two real world case studies: (i) the evolving author community of quantum game
      theory, as defined by Google Scholar (ii) a snapshot of the high energy physics
      (HEP) theory research community in arXiv. In both case studies, we find that the
      list of top authors vary very significantly when h-index and pagerank-index are
      used for comparison. We show that in both cases, authors who have collaborated in
      large groups and/or published less impactful papers tend to be comparatively
      favoured by the h-index, whereas the pagerank-index highlights authors who have
      made a relatively small number of definitive contributions, or written papers
      which served to highlight the link between diverse disciplines, or typically
      worked in smaller groups. Thus, we argue that the pagerank-index is an inherently
      fairer and more nuanced metric to quantify the publication records of scientists
      compared to existing measures. 

PMID- 26288314
TI  - Everything's Relative? Relative Differences in Processing Fluency and the Effects
      on Liking.
AB  - Explanations of aesthetic pleasure based on processing fluency have shown that
      ease-of-processing fosters liking. What is less clear, however, is how processing
      fluency arises. Does it arise from a relative comparison among the stimuli
      presented in the experiment? Or does it arise from a comparison to an internal
      reference or standard? To address these questions, we conducted two experiments
      in which two ease-of-processing manipulations were applied: either (1) within
      participants, where relative comparisons among stimuli varying in processing ease
      were possible, or (2) between-participants, where no relative comparisons were
      possible. In total, 97 participants viewed simple line drawings with high or low
      visual clarity, presented at four different presentation durations, and rated for
      felt fluency, liking, and certainty. Our results show that the manipulation of
      visual clarity led to differences in felt fluency and certainty regardless of
      being manipulated within- or between-participants. However, liking ratings were
      only affected when ease-of-processing was manipulated within-participants. Thus,
      feelings of fluency do not depend on the nature of the reference. On the other
      hand, participants liked fluent stimuli more only when there were other stimuli
      varying in ease-of-processing. Thus, relative differences in fluency seem to be
      crucial for liking judgments. 

PMID- 26288313
TI  - Moringa oleifera as an Anti-Cancer Agent against Breast and Colorectal Cancer
      Cell Lines.
AB  - In this study we investigated the anti-cancer effect of Moringa oleifera leaves,
      bark and seed extracts. When tested against MDA-MB-231 and HCT-8 cancer cell
      lines, the extracts of leaves and bark showed remarkable anti-cancer properties
      while surprisingly, seed extracts exhibited hardly any such properties. Cell
      survival was significantly low in both cells lines when treated with leaves and
      bark extracts. Furthermore, a striking reduction (about 70-90%) in colony
      formation as well as cell motility was observed upon treatment with leaves and
      bark. Additionally, apoptosis assay performed on these treated breast and
      colorectal cancer lines showed a remarkable increase in the number of apoptotic
      cells; with a 7 fold increase in MD-MB-231 to an increase of several fold in
      colorectal cancer cell lines. However, no significant apoptotic cells were
      detected upon seeds extract treatment. Moreover, the cell cycle distribution
      showed a G2/M enrichment (about 2-3 fold) indicating that these extracts
      effectively arrest the cell progression at the G2/M phase. The GC-MS analyses of
      these extracts revealed numerous known anti-cancer compounds, namely eugenol,
      isopropyl isothiocynate, D-allose, and hexadeconoic acid ethyl ester, all of
      which possess long chain hydrocarbons, sugar moiety and an aromatic ring. This
      suggests that the anti-cancer properties of Moringa oleifera could be attributed
      to the bioactive compounds present in the extracts from this plant. This is a
      novel study because no report has yet been cited on the effectiveness of Moringa
      extracts obtained in the locally grown environment as an anti-cancer agent
      against breast and colorectal cancers. Our study is the first of its kind to
      evaluate the anti-malignant properties of Moringa not only in leaves but also in
      bark. These findings suggest that both the leaf and bark extracts of Moringa
      collected from the Saudi Arabian region possess anti-cancer activity that can be
      used to develop new drugs for treatment of breast and colorectal cancers. 

PMID- 26288315
TI  - Synthesis of 4H/fcc-Au@Metal Sulfide Core-Shell Nanoribbons.
AB  - Although great advances on the synthesis of Au-semiconductor heteronanostructures
      have been achieved, the crystal structure of Au components is limited to the
      common face-centered cubic (fcc) phase. Herein, we report the synthesis of 4H/fcc
      Au@Ag2S core-shell nanoribbon (NRB) heterostructures from the 4H/fcc Au@Ag NRBs
      via the sulfurization of Ag. Remarkably, the obtained 4H/fcc-Au@Ag2S NRBs can be
      further converted to a novel class of 4H/fcc-Au@metal sulfide core-shell NRB
      heterostructures, referred to as 4H/fcc-Au@MS (M = Cd, Pb or Zn), through the
      cation exchange. We believe that these novel 4H/fcc-Au@metal sulfide NRB
      heteronanostructures may show some promising applications in catalysis, surface
      enhanced Raman scattering, solar cells, photothermal therapy, etc. 

PMID- 26288316
TI  - Bisphenol A and child and youth behaviour: Canadian Health Measures Survey 2007
      to 2011.
AB  - BACKGROUND: Bisphenol A (BPA) is a synthetic industrial chemical commonly used in
      consumer products. Results from the Canadian Heath Measures Survey (CHMS)
      indicate that more than 90% of children and youth aged 6 to 19 have detectable
      levels of urinary BPA. Childhood concentration levels of BPA have been linked
      with negative behavioural outcomes. DATA AND METHODS: The data are from the first
      two cycles (2007 to 2009 and 2009 to 2011) of the CHMS, which collected
      biomonitoring indicators via spot blood and urine samples. Behavioural outcomes-
      hyperactivity/inattention, emotional symptoms, conduct problems, peer problems,
      and prosocial behavior--were assessed with Goodman's Strengths and Difficulties
      Questionnaire. Geometric mean urinary BPA concentration was examined overall and
      by demographic and socioeconomic correlates. Six multiple logistic regression
      analyses were conducted to investigate associations between childhood BPA
      concentrations and risk status for each outcome. RESULTS: Children aged 6 to 8
      had higher BPA concentrations than did older children and youth. Concentrations
      were significantly higher among children and youth exposed to second-hand smoke
      every day or almost every day and those in low or lower-middle income households.
      Higher BPA concentrations were associated with increased odds of hyperactivity
      among girls and lower prosocial behaviour among boys. INTERPRETATION: These
      findings suggest an association between urinary BPA concentration and children's
      behavioural outcomes.

PMID- 26288317
TI  - Avoidable mortality among First Nations adults in Canada: A cohort analysis.
AB  - BACKGROUND: Avoidable mortality is a measure of deaths that potentially could
      have been averted through effective prevention practices, public health policies,
      and/or provision of timely and adequate health care. This longitudinal analysis
      compares avoidable mortality among First Nations and non-Aboriginal adults. DATA
      AND METHODS: Data are from the 1991-to-2006 Canadian Census Mortality and Cancer
      Follow-up Study. A 15% sample of 1991 Census respondents aged 25 or older was
      linked to 16 years of mortality data. This study examines avoidable mortality
      among 61,220 First Nations and 2,510,285 non-Aboriginal people aged 25 to 74.
      RESULTS: During the 1991-to-2006 period, First Nations adults had more than twice
      the risk of dying from avoidable causes compared with non-Aboriginal adults. The
      age-standardized avoidable mortality rate (ASMR) per 100,000 person-years at risk
      for First Nations men was 679.2 versus 337.6 for non-Aboriginal men (rate ratio =
      2.01). For women, ASMRs were lower, but the gap was wider. The ASMR for First
      Nations women was 453.2, compared with 183.5 for non-Aboriginal women (rate ratio
      = 2.47). Disparities were greater at younger ages. Diabetes, alcohol and drug use
      disorders, and unintentional injuries were the main contributors to excess
      avoidable deaths among First Nations adults. Education and income accounted for a
      substantial share of the disparities. INTERPRETATION: The results highlight the
      gap in avoidable mortality between First Nations and non-Aboriginal adults due to
      specific causes of death and the association with socioeconomic factors.

PMID- 26288318
TI  - Computational Study of Competition between Direct Abstraction and Addition
      Elimination in the Reaction of Cl Atoms with Propene.
AB  - Quasi-classical trajectory calculations on a newly constructed and full
      dimensionality potential energy surface (PES) examine the dynamics of the
      reaction of Cl atoms with propene. The PES is an empirical valence bond (EVB) fit
      to high-level ab initio energies and incorporates deep potential energy wells for
      the 1-chloropropyl and 2-chloropropyl radicals, a direct H atom abstraction route
      to HCl + allyl radical (CH2CHCH2(*)) products (Delta(r)H(298K)(?) = -63.1 kJ mol(
      1)), and a pathway connecting these regions. In total, 94 000 successful reactive
      trajectories were used to compute distributions of angular scattering and HCl
      vibrational and rotational level populations. These measures of the reaction
      dynamics agree satisfactorily with available experimental data. The dominant
      reaction pathway is direct abstraction of a hydrogen atom from the methyl group
      of propene occurring in under 500 fs. Less than 10% of trajectories follow an
      addition-elimination route via the two isomeric chloropropyl radicals. Large
      amplitude motions of the Cl about the propene molecular framework couple the
      addition intermediates to the direct abstraction pathway. The EVB method provides
      a good description of the complicated PES for the Cl + propene reaction despite
      fitting to a limited number of ab initio points, with the further advantage that
      dynamics specific to certain mechanisms can be studied in isolation by switching
      off coupling terms in the EVB matrix connecting different regions of the PES.

PMID- 26288319
TI  - Non-Lethal Heat Shock of the Asian Green Mussel, Perna viridis, Promotes Hsp70
      Synthesis, Induces Thermotolerance and Protects Against Vibrio Infection.
AB  - Mild heat stress promotes thermotolerance and protection against several
      different stresses in aquatic animals, consequences correlated with the
      accumulation of heat shock protein 70 (Hsp70). The purpose of this study was to
      determine if non-lethal heat shock (NLHS) of the Asian green mussel, Perna
      viridis, an aquatic species of commercial value, promoted the production of Hsp70
      and enhanced its resistance to stresses. Initially, the LT50 and LHT for P.
      viridis were determined to be 42 degrees C and 44 degrees C, respectively, with
      no heat shock induced death of mussels at 40 degrees C or less. Immunoprobing of
      western blots revealed augmentation of constitutive (PvHsp70-1) and inducible
      (PvHsp70-2) Hsp70 in tissue from adductor muscle, foot, gill and mantel of P.
      viridis exposed to 38 degrees C for 30 min followed by 6 h recovery, NLHS
      conditions for this organism. Characterization by liquid chromatography-tandem
      mass spectrometry (LC-MS/MS) revealed that PvHsp70-1 and PvHsp70-2 respectively
      corresponded most closely to Hsp70 from P. viridis and Mytilus galloprovincialis.
      Priming of adult mussels with NLHS promoted thermotolerance and increased
      resistance to V. alginolyticus. The induction of Hsp70 in parallel with enhanced
      thermotolerance and improved protection against V. alginolyticus, suggests Hsp70
      functions in P. viridis as a molecular chaperone and as a stimulator of the
      immune system. 

PMID- 26288320
TI  - Enantioselective synthesis of monofluorinated allylic compounds: Pd-catalyzed
      asymmetric allylations of dimethyl 2-fluoromalonate using new N-sulfinyl-based
      ligands.
AB  - New chiral S,N- and S,P-ligands starting from tert-butanesulfinamide were
      synthesized in four steps, applying Pd-catalyzed asymmetric allylic substitutions
      of dimethyl 2-fluoromalonate. The induced effect of the Pd/S,N-ligand catalyst on
      the enantioselectivity depends on the steric demand of the substituent at the o
      position of the pyridine ring. This method produced monofluorinated allylation
      products in up to high yield with high enantioselectivity. 

PMID- 26288322
TI  - Correction: Histamine 1 Receptor Blockade Enhances Eosinophil-Mediated Clearance
      of Adult Filarial Worms.

PMID- 26288323
TI  - Selective Formation of Zigzag Edges in Graphene Cracks.
AB  - We report the thermally induced unconventional cracking of graphene to generate
      zigzag edges. This crystallography-selective cracking was observed for as-grown
      graphene films immediately following the cooling process subsequent to chemical
      vapor deposition (CVD) on Cu foil. Results from Raman spectroscopy show that the
      crack-derived edges have smoother zigzag edges than the chemically formed grain
      edges of CVD graphene. Using these cracks as nanogaps, we were also able to
      demonstrate the carrier tuning of graphene through the electric field effect.
      Statistical analysis of visual observations indicated that the crack formation
      results from uniaxial tension imparted by the Cu substrates together with the
      stress concentration at notches in the polycrystalline graphene films. On the
      basis of simulation results using a simplified thermal shrinkage model, we
      propose that the cooling-induced tension is derived from the transient lattice
      expansion of narrow Cu grains imparted by the thermal shrinkage of adjacent Cu
      grains. 

PMID- 26288324
TI  - Correlation of serum cardiac troponin I and acute phase protein concentrations
      with clinical staging in dogs with degenerative mitral valve disease.
AB  - BACKGROUND: Cardiac troponin I (cTnI) correlates with severity of myocardial
      injury. Nonspecific inflammation in congestive heart failure (CHF) could be
      assessed by C-reactive protein (CRP), haptoglobin (Hp), and ceruloplasmin (Cp)
      measurements. OBJECTIVES: The aim of the study was to determine whether serum
      cTnI, CRP, Hp, and Cp concentrations differ among various stages of mitral valve
      disease (MVD) in dogs. MATERIALS AND METHODS: Dogs with MVD were allocated to 3
      groups (I - asymptomatic; II - mild to moderate CHF; III advanced CHF) according
      to the scheme of the International Small Animal Cardiac Healthy Council (ISACHC).
      Concentrations of cTnI, CRP, Cp, and Hp were measured in all dogs upon admission,
      and cTnI and CRP were measured bimonthly during a 4-month follow-up period.
      RESULTS: In total 46 dogs with MVD were enrolled for the cross-sectional part (21
      Group I, 11 Group II, 14 Group III), and 35 dogs were included in the
      longitudinal study. Initial mean Cp concentrations were similar among all groups.
      There was a statistically significant difference in Hp and CRP concentrations
      between group I (n = 21, P = .019) and III (n = 14, P < .001). There was a
      statistically significant decrease in CRP (P = .033) and cTnI (P = .009)
      concentrations over the longitudinal study (all groups). CRP concentrations were
      significantly higher in group I than III (P = .004). During the 6-month
      monitoring period of 35 dogs, there was a statistically significant positive
      correlation between cTnI and CRP (P < .001). CONCLUSION: Differences in CRP
      concentrations between clinical stages of MVD suggest a clinically and
      therapeutically relevant inflammatory component.

PMID- 26288325
TI  - A 30-Year Follow-Up of Partial Removable Dental Prostheses in a University Dental
      School Setting.
AB  - PURPOSE: To describe the pattern of partial removable dental prosthesis (PRDP)
      designs over a 30-year period in a cohort of patients from the Universite de
      Montreal, Faculty of Dentistry and to examine the effect of this design in PRDP
      complaints and the required treatment in a subsample of the patients' cohort.
      MATERIALS AND METHODS: In this retrospective descriptive study, 1380 PRDP
      laboratory prescriptions (1980-2009) and 131 PRDP clinical complaint forms (2006
      2008) from the archives of the undergraduate prosthodontics clinic of Universite
      de Montreal were selected. Data on type of PRDPs, design, PRDP-related
      complaints, and the need for treatment were collected. Descriptive statistics and
      bivariate statistical analyses were conducted. RESULTS: U-shaped (54%) and
      lingual plate (94%) were the most common major connectors used in the maxillary
      and mandibular arch, respectively. In 95% of laboratory prescriptions,
      circumferential clasp was the design for the retainers. Fracture of PRDP
      components was the most common (41%) complaint. Most of the complaints (68%) were
      made by PRDP wearers having natural teeth in the opposing arch. There was a
      significant relationship between fracture of PRDP components and having opposing
      natural teeth (p = 0.002). Seventy-three percent of PRDP-related complaints were
      manageable only by minor treatments such as repair, readjustments, and oral
      hygiene instructions. CONCLUSION: Changes in the design of PRDPs were noticeable
      at the Universite de Montreal since 1980, but there has been little change in the
      last 20 years. Biomechanical concepts and optimum hygiene were the basic elements
      in the design of RDPs in this university-based dental school setting. The
      majority of the complaints were treated by minor treatments.

PMID- 26288326
TI  - Gender differences in the magnitude of the associations between eating disorders
      symptoms and depression and anxiety symptoms. Results from a community sample of
      adolescents.
AB  - BACKGROUND: Studies reporting comorbidities of eating disorders (EDs) with
      depression and anxiety disorders during adolescence used clinical samples of
      female adolescents with few attempts to present the magnitude of these
      associations in population-based samples and to assess gender differences in the
      strength of these associations. AIMS: This study assesses significant gender
      differences in the association of anorexia nervosa (AN) and bulimia nervosa (BN)
      symptoms with depression and generalized anxiety symptoms in a community sample
      of adolescents. METHOD: We collected anonymous self-reported data from 235
      adolescent boys and 471 adolescent girls, through an online platform. To identify
      correlations between symptoms of AN and BN, and symptoms of depression and
      generalized anxiety, we used the Mann-Whitney U test. To identify differences
      between independent correlation coefficients, we converted each correlation
      coefficient into a z-score using Fisher's r-to-z transformation and, making use
      of the sample size employed to obtain each coefficient, we compared the z-scores.
      RESULTS: The magnitude of the associations between EDs symptomatology and
      depression and anxiety symptomatology was similar in adolescent boys and girls.
      CONCLUSION: Our results show an urgent need to address EDs prevention in
      adolescent girls and boys from the community.

PMID- 26288328
TI  - A remarkable exercise test leading to the diagnosis of left atrial myxoma.

PMID- 26288327
TI  - Chemokine ligand 9 modulates cardiac repolarization via Cxcr3 receptor binding.

PMID- 26288329
TI  - Tackling the bends in transcatheter aortic valve implantation.

PMID- 26288330
TI  - Microvascular dysfunction in Takotsubo cardiomyopathy: Prognostic implications.

PMID- 26288332
TI  - Sandpapery Skin.

PMID- 26288333
TI  - Ankle Accelerometry for Assessing Physical Activity Among Adolescent Girls:
      Threshold Determination, Validity, Reliability, and Feasibility.
AB  - PURPOSE: Ankle accelerometry allows for 24-hr data collection and improves data
      volume/integrity versus hip accelerometry. Using Actical ankle accelerometry, the
      purpose of this study was to (a) develop sensitive/specific thresholds, (b)
      examine validity/reliability, (c) compare new thresholds with those of the
      manufacturer, and (d) examine feasibility in a community sample (low-income,
      urban adolescent girls). METHOD: Two studies were conducted with 6th- through 7th
      grade girls (aged 10-14 years old): First was a laboratory study (n = 24), in
      which 2 Actical accelerometers were placed on the ankle and worn while measuring
      energy expenditure (Cosmed K4b2, metabolic equivalents [METs]) during 10
      prescribed activities. Analyses included device equivalence reliability
      (intraclass correlation coefficient [ICC], activity counts of 2 Acticals),
      criterion-related validity (correlation, activity counts and METs), and
      calculations of sensitivity, specificity, kappa, and receiver-operating
      characteristic curves for thresholds. The second was a free-living study (n =
      459), in which an Actical was worn for more than 7 days on the ankle (full 24-hr
      days retained). Analyses included feasibility (frequencies, missing data) and
      paired t tests (new thresholds vs. those of the manufacturer). RESULTS: In the
      laboratory study, the Actical demonstrated reliability (ICC = .92) and validity
      (r = .81). Thresholds demonstrated sensitivity (91%), specificity (84%), kappa =
      .73 (p = .043), area under curve range = .81-.97. In the free-living study, 99.6%
      of participants wore the accelerometer; 84.1% had complete/valid data (mean = 5.7
      days). Primary reasons for missing/invalid data included: improper
      programming/documentation (5.2%), failure to return device (5.0%), and wear-time
      <= 2 days (2.8%). The moderate-to-vigorous physical activity threshold (> 3,200
      counts/minute) yielded 37.2 min/day, 2 to 4.5 times lower than that of the
      manufacturer's software (effect size = 0.74-4.05). CONCLUSIONS: Validity,
      reliability, and feasibility evidences support Actical ankle accelerometry to
      assess physical activity in community studies of adolescent girls. When comparing
      manufacturers' software versus new thresholds, a major difference was observed.

PMID- 26288334
TI  - HBV-DNA levels predict overall mortality in HIV/HBV coinfected individuals.
AB  - The coinfection of Hepatitis B virus (HBV) and human immunodeficiency virus (HIV)
      has been associated with increased death rates. However, the relevant research
      has mostly relied on serologic HBV testing [HBV surface antigen (HBsAg)]. The aim
      of this work was to explore the relationship of HBV viraemia with overall
      mortality among HIV/HBV coinfected individuals. The analysis included 1,609 HIV
      seropositives of a previously described cohort (1984-2003) with limited exposure
      to tenofovir (12%) and a median follow-up of approximately 5 years. Those with
      persistent expression of HBsAg were further tested for HBV-DNA. The data were
      analyzed using Poisson regression models. Totally, 101 participants were chronic
      carriers of HBsAg (6.28%). Of these, 81 were tested for HBV-DNA. The median HBV
      DNA levels were 3.81 log (base-10) International Units (IU)/ml. A third (31%) of
      those tested for HBV-DNA had received tenofovir. Before developing acquired
      immune deficiency syndrome (AIDS), the adjusted incidence rate ratio (IRR) for
      all-cause mortality of coinfected patients with HBV viraemia above the median
      value versus the HIV monoinfected group was 3.44 [95% confidence interval (CI):
      1.05-11.27]. Multivariable regressions in the coinfected group only (n = 81)
      showed that one log-10 increase in HBV-DNA levels was associated with an elevated
      risk for death (IRR: 1.24, 95%CI: 1.03-1.49). HBV-DNA levels predict overall
      mortality in the setting of HIV/HBV coinfection, especially during the period
      before developing AIDS, and could thus help prioritize needs and determine the
      frequency of medical monitoring.

PMID- 26288335
TI  - Reproductive outcomes after hydatiform mole and gestational trophoblastic
      neoplasia.
AB  - Gestational trophoblastic disease includes complete hydatidiform mole (CHM) or
      partial hydatidiform mole (PHM) and gestational trophoblastic neoplasia (GTN).
      Given the very high-curability rate of trophoblastic disease, the risk of further
      molar pregnancy after CHM or PHM as well as the risk of second primary tumors and
      fertility compromise after chemotherapy for GTN represent major concerns. The
      incidence of subsequent molar pregnancy ranges from 0.7 to 2.6% after one CHM or
      PHM, and is approximately 10% after two previous CHMs. Among patients who have
      received chemotherapy, there is an increased risk of myeloid leukemia which is
      mainly related to the cumulative dose of etoposide. Resumption of normal menses
      occurs in approximately 95% of women treated with chemotherapy, but menopause
      occurs 3 years earlier compared with those non-treated with chemotherapy. Term
      live birth rates higher than 70% without increased risk of congenital
      abnormalities have been reported in these women, and pregnancy outcomes are
      comparable to those of general population, except a slightly increased risk of
      stillbirth. Fertility-sparing treatment for placental site trophoblastic tumor is
      a therapeutic option reserved to highly selected, young women who do not present
      markedly enlarged uterus or diffuse multifocal disease within the uterus. 

PMID- 26288336
TI  - A highly sensitive, low-cost, wearable pressure sensor based on conductive
      hydrogel spheres.
AB  - Wearable pressure sensing solutions have promising future for practical
      applications in health monitoring and human/machine interfaces. Here, a highly
      sensitive, low-cost, wearable pressure sensor based on conductive single-walled
      carbon nanotube (SWCNT)/alginate hydrogel spheres is reported. Conductive and
      piezoresistive spheres are embedded between conductive electrodes (indium tin
      oxide-coated polyethylene terephthalate films) and subjected to environmental
      pressure. The detection mechanism is based on the piezoresistivity of the
      SWCNT/alginate conductive spheres and on the sphere-electrode contact. Step-by
      step, we optimized the design parameters to maximize the sensitivity of the
      sensor. The optimized hydrogel sensor exhibited a satisfactory sensitivity (0.176
      DeltaR/R0/kPa(-1)) and a low detectable limit (10 Pa). Moreover, a brief response
      time (a few milliseconds) and successful repeatability were also demonstrated.
      Finally, the efficiency of this strategy was verified through a series of
      practical tests such as monitoring human wrist pulse, detecting throat muscle
      motion or identifying the location and the distribution of an external pressure
      using an array sensor (4 * 4). 

PMID- 26288338
TI  - Computational Insight into the Mechanism of Alkane Hydroxylation by Non-heme
      Fe(PyTACN) Iron Complexes. Effects of the Substrate and Solvent.
AB  - The reaction mechanisms for alkane hydroxylation catalyzed by non-heme Fe(V)O
      complexes presented in the literature vary from rebound stepwise to concerted
      highly asynchronous processes. The origin of these important differences is still
      not completely understood. Herein, in order to clarify this apparent
      inconsistency, the hydroxylation of a series of alkanes (methane and substrates
      bearing primary, secondary, and tertiary C-H bonds) through a Fe(V)O species,
      [Fe(V)(O)(OH)(PyTACN)](2+) (PyTACN = 1-(2'-pyridylmethyl)-4,7-dimethyl-1,4,7
      triazacyclononane), has been computationally examined at the gas phase and in
      acetonitrile solution. The initial breaking of the C-H bond can occur via
      hydrogen atom transfer (HAT), leading to an intermediate where there is an
      interaction between the radical substrate and [Fe(IV)(OH)2(PyTACN)](2+), or
      through hydride transfer to form a cationic substrate interacting with the
      [Fe(III)(OH)2(PyTACN)](+) species. Our calculations show the following: (i)
      except for methane in the rest of the alkanes studied, the intermediate formed by
      R(+) and [Fe(III)(OH)2(PyTACN)](+) is more stable than that involving the alkyl
      radical and the [Fe(IV)(OH)2(PyTACN)](2+) complex; (ii) in spite of (i), the
      first step of the reaction mechanism for all substrates is a HAT instead of
      hydride abstraction; (iii) the HAT is the rate-determining step for all analyzed
      cases; and (iv) the barrier for the HAT decreases along methane -> primary ->
      secondary -> tertiary carbon. The second part of the reaction mechanism
      corresponds to the rebound process. Therefore, the stereospecific hydroxylation
      of alkane C-H bonds by non-heme Fe(V)(O) species occurs through a rebound
      stepwise mechanism that resembles that taking place at heme analogues. Finally,
      our study also shows that, to properly describe alkane hydroxylation processes
      mediated by Fe(V)O species, it is essential to consider the solvent effects
      during geometry optimizations. The use of gas-phase geometries explains the
      variety of mechanisms for the hydroxylation of alkanes reported in the
      literature. 

PMID- 26288339
TI  - Correction: Correlation between hierarchical structure of crystal networks and
      macroscopic performance of mesoscopic soft materials and engineering principles.
AB  - Correction for 'Correlation between hierarchical structure of crystal networks
      and macroscopic performance of mesoscopic soft materials and engineering
      principles' by Naibo Lin et al., Chem. Soc. Rev., 2015, DOI: . 

PMID- 26288337
TI  - Periostin and TGF-beta-induced protein: Two peas in a pod?
AB  - Periostin (PN) and TGF-beta-induced protein (betaig-h3) are paralogs that contain
      a single emilin and four fasciclin-1 modules and are secreted from cells. PN
      receives attention because of its up-regulation in cancer and degenerative and
      allergic diseases. betaig-h3 is highly enriched in cornea and best known for
      harboring mutations in humans associated with corneal dystrophies. Both proteins
      are expressed widely, and many functions, some over-lapping, have been attributed
      to PN and betaig-h3 based on biochemical, cell culture, and whole animal
      experiments. We attempt to organize this knowledge so as to facilitate research
      on these interesting and incompletely understood proteins. We focus particularly
      on whether PN and betaig-h3 are modified by vitamin K-dependent gamma-glutamyl
      carboxylation, a question of considerable importance given the profound effects
      of gamma-carboxylation on structure and function of other proteins. We consider
      the roles of PN and betaig-h3 in formation of extracellular matrix and as ligands
      for integrin receptors. We attempt to reconcile the contradictory results that
      have arisen concerning the role of PN, which has emerged as a marker of TH2
      immunity, in murine models of allergic asthma. Finally, when possible we compare
      and contrast the structures and functions of the two proteins. 

PMID- 26288340
TI  - Ultrasound-Guided Percutaneous Vein Access for Placement of Broviac Catheters in
      Extremely Low Birth Weight Neonates: A Series of 3 Successful Cases.
AB  - As medical and surgical interventions to support premature infants have evolved,
      the need for long-term vascular access in extremely low birth weight infants has
      increased. The classic approach to Broviac((r)) (C.R. Bard, Covington, GA)
      catheter placement in very small neonates has been through an open surgical
      cutdown technique. Ultrasound guidance has emerged as a potentially beneficial
      method for obtaining central venous access in children and is being applied to
      smaller and smaller infants. This case series reports the feasibility of using
      ultrasound-guided percutaneous vein access to obtain a long-term central venous
      line in three extremely low birth weight infants who all weighed less than 850 g
      at the time of line placement.

PMID- 26288341
TI  - Building a scholar in writing (BSW): A model for developing students' critical
      writing skills.
AB  - Several authors have highlighted the importance of writing in developing
      reflective thinking skills, transforming knowledge, communicating expressions,
      and filling knowledge gaps. However, difficulties with higher order processing
      and critical analysis affect students' ability to write critical and thoughtful
      essays. The Building a Scholar in Writing (BSW) model is a 6-step process of
      increasing intricacies in critical writing development. Development of critical
      writing is proposed to occur in a processed manner that transitions from
      presenting simple ideas (just bones) in writing, to connecting ideas (connecting
      bones), to formulating a thesis and connecting key components (constructing a
      skeleton), to supporting ideas with evidence (adding muscle), to building
      creativity and originality (adding essential organs), and finally, developing
      strong, integrated, critical arguments (adding brain). This process symbolically
      represents the building of a scholar. The idea of building a scholar equates to
      progressively giving life and meaning to a piece of writing with unique scholarly
      characteristics. This progression involves a transformation in awareness,
      thinking, and understanding, as well as advancement in students' level of
      critical appraisal skills. 

PMID- 26288342
TI  - Activation of Homolytic Si-Zn and Si-Hg Bond Cleavage, Mediated by a Pt(0)
      Complex, via Novel Pt-Zn and Pt-Hg Compounds.
AB  - The thermally stable [(tBuMe2 Si)2 M] (M=Zn, Hg) generate R3 Si(.) radicals in
      the presence of [(dmpe)Pt(PEt3 )2 ] at 60-80  degrees C. The reaction proceeds
      via hexacoordinate Pt complexes, (M=Zn (2 a and 2 b), M=Hg (3 a and 3 b)) which
      were isolated and characterized. Mild warming or photolysis of 2 or 3 lead to
      homolytic dissociation of the Pt-MSiR3 bond generating silyl radicals and novel
      unstable pentacoordinate platinum paramagnetic complexes (M=Zn (5), Hg (6)) whose
      structures were determined by EPR spectroscopy and DFT calculations.

PMID- 26288343
TI  - Age-related changes in natural killer cell repertoires: impact on NK cell
      function and immune surveillance.
AB  - A key feature of human natural killer (NK) cells, which enables efficient
      recognition of infected and malignant target cells, is the expression of HLA
      class I-specific receptors of the KIR and NKG2 gene families. Cell-to-cell
      variability in receptor expression leads to the formation of complex NK cell
      repertoires. As outlined here, NK cells go through major changes from newborns to
      adults characterized by downregulation of the inhibitory NKG2A receptor and
      concomitant upregulation of KIR family members. This process is completed in
      young adults, and in the majority of individuals, KIR/NKG2A repertoires remain
      remarkably stable until old age. Nonetheless, age-related factors have the
      potential to majorly influence the complexity of NK cell repertoires: Firstly
      infection with HCMV is associated with major clonal expansions of terminally
      differentiated NKG2C- and KIR-expressing NK cells in certain individuals.
      Secondly, ineffective hematopoiesis can lead to immature and less diversified NK
      cell repertoires as observed in myelodysplastic syndrome (MDS), a malignant
      disease of the elderly. Thus, whereas in the majority of elderly the NK cell
      compartment appears to be highly stable in terms of function and phenotype, in a
      minority of subjects a breakdown of NK cell repertoire diversity is observed that
      might influence immune surveillance and healthy aging. 

PMID- 26288344
TI  - Discovery and Optimization of 4-(8-(3-Fluorophenyl)-1,7-naphthyridin-6
      yl)transcyclohexanecarboxylic Acid, an Improved PDE4 Inhibitor for the Treatment
      of Chronic Obstructive Pulmonary Disease (COPD).
AB  - Herein we describe the optimization of a series of PDE4 inhibitors, with special
      focus on solubility and pharamcokinetics, to clinical compound 2, 4-(8-(3
      fluorophenyl)-1,7-naphthyridin-6-yl)transcyclohexanecarboxylic acid. Although
      compound 2 produces emesis in humans when given as a single dose, its exemplary
      pharmacokinetic properties enabled a novel dosing regime comprising multiple
      escalating doses and the resultant achievement of high plasma drug levels without
      associated nausea or emesis. 

PMID- 26288345
TI  - Premonitory Urges in Patients with Gilles de la Tourette Syndrome: An Italian
      Translation and a 7-Year Follow-up.
AB  - OBJECTIVE: Premonitory sensations or urges (PUs) are described as characteristic
      sensory phenomena preceding tics, which are often described as unpleasant. They
      occur in 90% of patients affected by Gilles de la Tourette Syndrome (GTS). They
      may be localized (around the area of tic) or generalized (covering a wide area of
      the body). The PUs can be measured by the Premonitory Urge for Tics Scale (PUTS).
      In this study we translated the PUTS scale into Italian and then assessed
      children and adolescents/young people (CYP) with GTS using the scale. METHODS:
      GTS patients were assessed at the initial interview and after 7 years to evaluate
      the PUs, and the correlations of the PUTS scores with tic severity, severity of
      comorbid disorders (obsessive-compulsive disorder [OCD], attention
      deficit/hyperactivity disorder [ADHD]), and a variety of coexisting
      psychopathologies. RESULTS: A total of 95 patients were studied. We successfully
      translated the PUTS into Italian, and our results indicated that our translated
      version had good psychometric properties. Results demonstrated that the CYP had
      PUs at both interviews, but that older CYP were more consistent in reporting PUs
      than younger CYP (i.e., PUTS scores increased with age). We found no correlations
      between PUTS score and tic severity at either interview. We found a statistical
      significant correlation between PUTS score and obsessive-compulsive symptoms
      (OCS) at both interviews; Moreover both the PUTS and Children's Yale-Brown
      Obsessive Compulsive Scale (CY-BOCS) scores increased significantly, whereas the
      Yale Global Tic Severity Rating Scale (YGTSS) score decreased significantly. We
      found no relationships between PUTS scores and anxiety, depression, ADHD, and
      externalizing/internalizing behavioral scores. CONCLUSIONS: Our results suggest
      the the Italian translation of the PUTS has good psychometric properties.
      Although both younger (<10 years of age) and older CYP (<= 10 years of age)
      reported PUs, the scores at the initial interview were statistically
      significantly lower than at follow-up. Moreover, in CYP >10 years of age, the PUs
      correlated with obsessions and compulsions (CY-BOCS scores).

PMID- 26288348
TI  - Exoelectrogens Leading to Precise Reduction of Graphene Oxide by Flexibly
      Switching Their Environment during Respiration.
AB  - Reduced graphene oxide (RGO) has been prepared by a simple, cost-effective, and
      green route. In this work, graphene oxide (GO) has been reduced using Gram
      negative facultative anaerobe S. dysenteriae, having exogenic properties of
      electron transfer via electron shuttling. Apparently, different concentrations of
      GO were successfully reduced with almost complete mass recovery. An effective
      role of lipopolysaccharide has been observed while comparing RGO reduced by S.
      dysenteriae and S. aureus. It was observed that the absence of lipopolysaccharide
      in Gram-positive S. aureus leads to a disrupted cell wall and that S.aureus could
      not survive in the presence of GO, leading to poor and inefficient reduction of
      GO, as shown in our results. However, S. dysenteriae having an outer
      lipopolysaccharide layer on its cell membrane reduced GO efficiently and the
      reduction process was extracellular for it. RGO prepared in our work has been
      characterized by X-ray diffraction, zeta potential, X-ray photoelectron
      spectroscopy, and Raman spectroscopy techniques, and the results were found to be
      in good agreement with those of chemically reduced GO. As agglomeration of RGO is
      the major issue to overcome while chemically reducing GO, we observed that RGO
      prepared by a bacterial route in our work has zeta potential value of -26.62 mV,
      good enough to avoid restacking of RGO. The role of exoelectrogens in electron
      transfer in the extracellular space has been depicted. Toxin released
      extracellularly during the process paves the way for reduction of GO due to its
      affinity towards oxygen. 

PMID- 26288346
TI  - Survey of Common Aesthetic Practices Among Oculofacial Surgeons in Parts of the
      Asia-Pacific.
AB  - PURPOSE: An anonymous Web-based survey was performed to assess the current
      practices, preferences, and complications of aesthetic procedures encountered by
      oculofacial surgeons in the Asia-Pacific. Results were compared with a similar
      study carried out in 2007 among members of the American Society of Ophthalmic
      Plastic and Reconstructive Surgery (ASOPRS). DESIGN: This was a cross-sectional
      survey study. METHODS: The study survey was sent out via e-mail to 131
      oculofacial surgeons in 14 countries in the Asia-Pacific. Survey questions
      included the demographics of survey respondents, practices, preferences, and
      complications of aesthetic procedures encountered by the surgeons. RESULTS:
      Seventy-four respondents (56.5%) attempted the survey between May and December
      2012. Only completed surveys (43 surveys) were included in our analysis. Eighty
      six percent of respondents performed aesthetic procedures in their practice. The
      top 3 most common nonsurgical procedures reported were injection of botulinum
      toxin (94.1% of respondents), tissue fillers (61.8%), and skin resurfacing
      (11.8%), whereas the top 3 most common surgical procedures reported were
      blepharoplasty (100% of respondents), brow lift (94.6%), and midface lift
      (29.7%). CONCLUSIONS: The majority of our study respondents performed aesthetic
      procedures in their practice. The percentage of practices that comprised
      aesthetics services was lower than that seen in the ASOPRS study. The percentage
      of respondents who performed injection of botulinum toxin, tissue fillers, brow
      lifts, and thread lifts were similar to those in the ASOPRS study; however, the
      percentage of respondents who performed ablative skin resurfacing was much lower.

PMID- 26288349
TI  - Whole-exome sequencing identifies novel autosomal recessive DSG1 mutations
      associated with mild SAM syndrome.

PMID- 26288350
TI  - Increased Susceptibility to Skin Carcinogenesis Associated with a Spontaneous
      Mouse Mutation in the Palmitoyl Transferase Zdhhc13 Gene.
AB  - Here we describe a spontaneous mutation in the Zdhhc13 (zinc finger, DHHC domain
      containing 13) gene (also called Hip14l), one of 24 genes encoding palmitoyl
      acyltransferase (PAT) enzymes in the mouse. This mutation (Zdhhc13luc) was
      identified as a nonsense base substitution, which results in a premature stop
      codon that generates a truncated form of the ZDHHC13 protein, representing a
      potential loss-of-function allele. Homozygous Zdhhc13luc/Zdhhc13luc mice
      developed generalized hypotrichosis, associated with abnormal hair cycle,
      epidermal and sebaceous gland hyperplasia, hyperkeratosis, and increased
      epidermal thickness. Increased keratinocyte proliferation and accelerated transit
      from basal to more differentiated layers were observed in mutant compared with
      wild-type (WT) epidermis in untreated skin and after short-term 12-O
      tetradecanoyl-phorbol-13-acetate treatment and acute UVB exposure. Interestingly,
      this epidermal phenotype was associated with constitutive activation of NF-kappaB
      (RelA) and increased neutrophil recruitment and elastase activity. Furthermore,
      tumor multiplicity and malignant progression of papillomas after chemical skin
      carcinogenesis were significantly higher in mutant mice than WT littermates. To
      our knowledge, this is the first report of a protective role for PAT in skin
      carcinogenesis.

PMID- 26288351
TI  - Activation of the Thromboxane A2 Receptor by 8-Isoprostane Inhibits the Pro
      Angiogenic Effect of Vascular Endothelial Growth Factor in Scleroderma.
AB  - The pathogenesis of scleroderma (SSc) includes components of autoimmunity,
      vascular dysfunction, and accumulation of extracellular matrix. 8-isoprostane, an
      oxidized lipid created by oxidative stress, activates the thromboxane A2 receptor
      (TXAR) and the Rho-associated kinase (ROCK) pathway. In this study, we determined
      whether the TXAR was activated by 8-isoprostane in SSc endothelial cells (ECs)
      and whether this pathway inhibited VEGF-induced angiogenesis. Elevated 8
      isoprostane was observed in plasma and conditioned media from SSc patients. SSc
      conditioned media inhibited EC tube formation, whereas addition of vitamin E, by
      reducing 8-isoprostane, increased tube formation. VEGF did not induce
      angiogenesis in SSc ECs, but vitamin E or TXAR inhibition restored its effect.
      The expression of TXAR, RhoA, and ROCK1/2 was elevated in SSc ECs. ROCK activity
      and 8-isoprostane-induced ROCK activation were significantly higher in SSc ECs,
      whereas VEGF had no effect. The hyper-activation of the TXAR leads to inhibition
      of VEGF-induced angiogenesis, as inhibition of the TXAR pathway results in a
      blockade of 8-isoprostane-induced ROCK activation and restoration of VEGF
      activity. These results suggest that the TXAR pathway has a crucial role in
      angiogenesis and that 8-isoprostane is not just a by-product of oxidative stress
      but also has a significant role in the impaired angiogenesis that characterizes
      SSc. 

PMID- 26288352
TI  - Loss of Desmoglein Binding Is Not Sufficient for Keratinocyte Dissociation in
      Pemphigus.
AB  - Pemphigus vulgaris (PV) is a severe autoimmune disease in which autoantibodies
      against the desmosomal cell adhesion molecules desmoglein (Dsg) 1 and Dsg3 cause
      intraepidermal blister formation. Mechanistically, the fundamental question is
      still unresolved whether loss of cell cohesion is a result of (1) direct
      inhibition of Dsg interaction by autoantibodies or (2) intracellular signaling
      events, which are altered in response to antibody binding and finally cause
      desmosome destabilization. We used atomic force microscopy (AFM) to perform Dsg3
      adhesion measurements on living keratinocytes to investigate the contributions of
      direct inhibition and signaling to loss of cell cohesion after autoantibody
      treatment. Dsg3 binding was rapidly blocked following antibody exposure under
      conditions where no depletion of surface Dsg3 was detectable, demonstrating
      direct inhibition of Dsg3 interaction. Inhibition of p38MAPK, a central signaling
      molecule in PV pathogenesis, abrogated loss of cell cohesion, but had a minor
      effect on loss of Dsg3 binding. Similarly, the cholesterol-depleting agent methyl
      beta-cyclodextrin (beta-MCD) fully blocked cell dissociation, but did not restore
      Dsg3 interactions or prevent the activation of p38MAPK. These results demonstrate
      that inhibition of Dsg3 binding is not sufficient to cause loss of cell cohesion,
      but rather alters signaling events which, in lipid raft-dependent manner, induce
      cell dissociation. 

PMID- 26288353
TI  - IFNlambda Stimulates MxA Production in Human Dermal Fibroblasts via a MAPK
      Dependent STAT1-Independent Mechanism.
AB  - IFNlambda is important for epidermal defense against viruses. It is produced by,
      and acts on, keratinocytes, whereas fibroblasts were previously considered to be
      unresponsive to this type III IFN. Herein we report findings revealing cell type
      specific differences in IFNlambda signaling and function in skin resident cells.
      In dermal fibroblasts, IFNlambda induced the expression of myxovirus protein A
      (MxA), a potent antiviral factor, but not other IFN signature genes as it does in
      primary keratinocytes. In contrast to its effect on keratinocytes, IFNlambda did
      not phosphorylate signal transducer and activator of transcription 1 in
      fibroblasts, but instead activated mitogen activated protein kinases (MAPK).
      Accordingly, inhibition of MAPK activation (p38 and p42/44) blocked the
      expression of MxA protein in fibroblasts but not in keratinocytes. Functionally,
      IFNlambda inhibited proliferation in keratinocytes but not in fibroblasts.
      Moreover, IFNlambda upregulated the expression of Tumor growth factor beta 1
      (TGFbeta1)-induced collagens in fibroblasts. Taken together, our findings
      identify primary human dermal fibroblasts as responder cells to IFNlambda. Our
      study shows cutaneous cell type-specific IFN signaling and suggests that
      IFNlambda, although important for epidermal antiviral competence, may also have a
      regulatory role in the dermal compartment balancing type I IFN-induced inhibition
      of tissue repair processes. 

PMID- 26288354
TI  - TSLP Directly Interacts with Skin-Homing Th2 Cells Highly Expressing its Receptor
      to Enhance IL-4 Production in Atopic Dermatitis.
AB  - Thymic stromal lymphopoietin (TSLP) is overtly expressed on skin lesions of
      atopic dermatitis (AD), and the initiative role of TSLP-activated DCs in AD has
      gained much attention in the past few years, while its actions on other immune
      cells such as T cells have been given less notice. We aimed to clarify whether
      TSLP receptor (TSLPR) is expressed on certain populations of T cells and whether
      TSLP possesses the capability to directly interact with T cells from AD patients.
      Peripheral lymphocytes from 51 AD patients are analyzed by flow cytometry, and ex
      vivo experiments using peripheral blood and lesional skin-derived T cells were
      conducted. TSLPR expression was defined to CD4+ T cells, and CD4+CCR4+CXCR3-CCR7
      CCR10+CLA+ T cells in AD patients exhibited enhanced TSLPR expression. The
      frequency of TSLPR+CD4+ T cells correlated with disease activity. CD4+ T cells
      from AD patients directly interacted with TSLP to produce a higher amount of IL-4
      than those from normal subjects, and this action was attenuated with anti-TSLPR
      antibody. The importance of IL-4 in the induction of TSLPR expression was found
      in AD T cells. Our findings indicate that T cells from AD patients possess strong
      potential to directly interact with TSLP to promote Th2 response.

PMID- 26288355
TI  - Suppression of Hyperactive Immune Responses Protects against Nitrogen Mustard
      Injury.
AB  - DNA alkylating agents like nitrogen mustard (NM) are easily absorbed through the
      skin and exposure to such agents manifest not only in direct cellular death but
      also in triggering inflammation. We show that toxicity resulting from topical
      mustard exposure is mediated in part by initiating exaggerated host innate immune
      responses. Using an experimental model of skin exposure to NM we observe
      activation of inflammatory dermal macrophages that exacerbate local tissue damage
      in an inducible nitric oxide synthase (iNOS)-dependent manner. Subsequently these
      activated dermal macrophages reappear in the bone marrow to aid in disruption of
      hematopoiesis and contribute ultimately to mortality in an experimental mouse
      model of topical NM exposure. Intervention with a single dose of 25
      hydroxyvitamin D3 (25(OH)D) is capable of suppressing macrophage-mediated iNOS
      production resulting in mitigation of local skin destruction, enhanced tissue
      repair, protection from marrow depletion, and rescue from severe precipitous
      wasting. These protective effects are recapitulated experimentally using
      pharmacological inhibitors of iNOS or by compounds that locally deplete skin
      macrophages. Taken together, these data highlight a critical unappreciated role
      of the host innate immune system in exacerbating injury following exposure to NM
      and support the translation of 25(OH)D in the therapeutic use against these
      chemical agents. 

PMID- 26288356
TI  - Tumor Ulceration Does Not Fully Explain Sex Disparities in Melanoma Survival
      among Adolescents and Young Adults.

PMID- 26288357
TI  - Fate of Prominin-1 Expressing Dermal Papilla Cells during Homeostasis, Wound
      Healing and Wnt Activation.
AB  - Prominin-1/CD133 (Prom1) is expressed by fibroblasts in the dermal papilla (DP)
      of the hair follicle (HF). By examining endogenous Prom1 expression and
      expression of LacZ in the skin of Prom1CreERLacZ (Prom1C-L) mice, in which a
      CreERT2-IRES-nuclear LacZ cassette is knocked into the first ATG codon of Prom1,
      we confirmed that Prom1 is expressed in the DP of all developing HFs and also by
      postnatal anagen follicles. To analyze the fate of Prom1+ DP cells, we crossed
      Prom1C-L mice with Rosa26-CAG flox/stop/flox tdTomato reporter mice and applied 4
      hydroxytamoxifen (4OHT) to back skin at postnatal day (P) 1 and P2. We detected
      tdTomato+ cells in ~50% of DPs. The proportion of labeled cells per DP increased
      between P5 and P63, while the total number of cells per DP declined. Following
      full thickness wounding, there was no migration of tdTomato-labeled cells out of
      the DP. When beta-catenin was activated in Prom1+ DP cells there was an increase
      in the size of anagen and telogen DP, but the proportion of tdTomato-labeled
      cells did not increase. We conclude that Prom1+ DP cells do not contribute to
      dermal repair but are nevertheless capable of regulating DP size via beta-catenin
      mediated intercellular communication.

PMID- 26288358
TI  - Keratinocyte Microvesicles Regulate the Expression of Multiple Genes in Dermal
      Fibroblasts.
AB  - Extracellular vesicles released from cells regulate many normal and pathological
      conditions. Little is known about the role of epidermal keratinocyte
      microvesicles (KC-MVs) in epithelial-stromal interaction that is essential for
      wound healing. We investigated, therefore, whether MV-like structures are present
      in human wounds and whether they affect wound healing-associated gene expression
      in dermal fibroblasts. In human wounds, MV-like vesicles were observed during
      active epithelial migration and early granulation tissue formation. When KC-MVs
      derived from keratinocyte-like cells (HaCaT) were added to fibroblast cultures,
      expression of 21 genes was significantly regulated (P<0.05) out of 80 genes
      investigated, including matrix metalloproteinase-1 and -3, interleukin-6 and -8,
      and genes associated with transforming growth factor-beta signaling. Similar
      changes were observed at the protein level. MVs from normal epidermal
      keratinocytes showed similar response to HaCaT cells. KC-MVs activated ERK1/2,
      JNK, Smad, and p38 signaling pathways in fibroblasts with ERK1/2 signaling having
      the most prominent role in the MV-induced gene expression changes. KC-MVs
      stimulated fibroblast migration and induced fibroblast-mediated endothelial tube
      formation but did not affect collagen gel contraction by fibroblasts. The results
      demonstrate that keratinocyte microvesicles have a strong and a specific
      regulatory effect on fibroblasts that may modulate several aspects of wound
      healing. 

PMID- 26288359
TI  - Macrophages Contribute to the Progression of Infantile Hemangioma by Regulating
      the Proliferation and Differentiation of Hemangioma Stem Cells.
AB  - Macrophage infiltration has been implicated in infantile hemangioma (IH), the
      most common tumor of infancy. However, the exact role of macrophages in IH
      remains unknown. This study aims to clarify the functional significance of
      macrophages in the progression of IH. The distribution of macrophages in human IH
      was analyzed, and our results revealed that polarized macrophages were more
      prevalent in proliferating IHs than in involuting IHs, which was consistent with
      the increased macrophage-related cytokines in proliferating IHs. In vitro results
      further demonstrated that polarized macrophages effectively promoted the
      proliferation of hemangioma stem cells (HemSCs) and suppressed their adipogenesis
      in an Akt- and extracellular signal-regulated kinase 1/2 (Erk1/2)-dependent
      manner. Moreover, M2- but not M1-polarized macrophages promoted the endothelial
      differentiation of HemSCs. Furthermore, mixing macrophages in a murine hemangioma
      model elevated microvessel density and postponed fat tissue formation, which was
      concomitant with the activation of Akt and Erk1/2 signals. Cluster analysis
      revealed a close correlation among the macrophage markers, Ki67, vascular
      endothelial growth factor (VEGF), p-Akt, and p-Erk1/2 in human IH tissues.
      Collectively, our results suggest that macrophages in IH contribute to tumor
      progression by promoting the proliferation and endothelial differentiation while
      suppressing the adipogenesis of HemSCs. These findings indicate that targeting
      the infiltrating macrophages in IH is a promising therapeutic approach to
      accelerate IH regression. 

PMID- 26288360
TI  - Sodiation Kinetics of Metal Oxide Conversion Electrodes: A Comparative Study with
      Lithiation.
AB  - The development of sodium ion batteries (NIBs) can provide an alternative to
      lithium ion batteries (LIBs) for sustainable, low-cost energy storage. However,
      due to the larger size and higher m/e ratio of the sodium ion compared to
      lithium, sodiation reactions of candidate electrodes are expected to differ in
      significant ways from the corresponding lithium ones. In this work, we
      investigated the sodiation mechanism of a typical transition metal-oxide, NiO,
      through a set of correlated techniques, including electrochemical and synchrotron
      studies, real-time electron microscopy observation, and ab initio molecular
      dynamics (MD) simulations. We found that a crystalline Na2O reaction layer that
      was formed at the beginning of sodiation plays an important role in blocking the
      further transport of sodium ions. In addition, sodiation in NiO exhibits a
      "shrinking-core" mode that results from a layer-by-layer reaction, as identified
      by ab initio MD simulations. For lithiation, however, the formation of Li
      antisite defects significantly distorts the local NiO lattice that facilitates Li
      insertion, thus enhancing the overall reaction rate. These observations delineate
      the mechanistic difference between sodiation and lithiation in metal-oxide
      conversion materials. More importantly, our findings identify the importance of
      understanding the role of reaction layers on the functioning of electrodes and
      thus provide critical insights into further optimizing NIB materials through
      surface engineering. 

PMID- 26288361
TI  - "Body-In-The-Loop": Optimizing Device Parameters Using Measures of Instantaneous
      Energetic Cost.
AB  - This paper demonstrates methods for the online optimization of assistive robotic
      devices such as powered prostheses, orthoses and exoskeletons. Our algorithms
      estimate the value of a physiological objective in real-time (with a body "in-the
      loop") and use this information to identify optimal device parameters. To handle
      sensor data that are noisy and dynamically delayed, we rely on a combination of
      dynamic estimation and response surface identification. We evaluated three
      algorithms (Steady-State Cost Mapping, Instantaneous Cost Mapping, and
      Instantaneous Cost Gradient Search) with eight healthy human subjects. Steady
      State Cost Mapping is an established technique that fits a cubic polynomial to
      averages of steady-state measures at different parameter settings. The optimal
      parameter value is determined from the polynomial fit. Using a continuous sweep
      over a range of parameters and taking into account measurement dynamics,
      Instantaneous Cost Mapping identifies a cubic polynomial more quickly.
      Instantaneous Cost Gradient Search uses a similar technique to iteratively
      approach the optimal parameter value using estimates of the local gradient. To
      evaluate these methods in a simple and repeatable way, we prescribed step
      frequency via a metronome and optimized this frequency to minimize metabolic
      energetic cost. This use of step frequency allows a comparison of our results to
      established techniques and enables others to replicate our methods. Our results
      show that all three methods achieve similar accuracy in estimating optimal step
      frequency. For all methods, the average error between the predicted minima and
      the subjects' preferred step frequencies was less than 1% with a standard
      deviation between 4% and 5%. Using Instantaneous Cost Mapping, we were able to
      reduce subject walking-time from over an hour to less than 10 minutes. While, for
      a single parameter, the Instantaneous Cost Gradient Search is not much faster
      than Steady-State Cost Mapping, the Instantaneous Cost Gradient Search extends
      favorably to multi-dimensional parameter spaces. 

PMID- 26288363
TI  - Selecting Populations for Non-Analogous Climate Conditions Using Universal
      Response Functions: The Case of Douglas-Fir in Central Europe.
AB  - Identifying populations within tree species potentially adapted to future
      climatic conditions is an important requirement for reforestation and assisted
      migration programmes. Such populations can be identified either by empirical
      response functions based on correlations of quantitative traits with climate
      variables or by climate envelope models that compare the climate of seed sources
      and potential growing areas. In the present study, we analyzed the intraspecific
      variation in climate growth response of Douglas-fir planted within the non
      analogous climate conditions of Central and continental Europe. With data from 50
      common garden trials, we developed Universal Response Functions (URF) for tree
      height and mean basal area and compared the growth performance of the selected
      best performing populations with that of populations identified through a climate
      envelope approach. Climate variables of the trial location were found to be
      stronger predictors of growth performance than climate variables of the
      population origin. Although the precipitation regime of the population sources
      varied strongly none of the precipitation related climate variables of population
      origin was found to be significant within the models. Overall, the URFs explained
      more than 88% of variation in growth performance. Populations identified by the
      URF models originate from western Cascades and coastal areas of Washington and
      Oregon and show significantly higher growth performance than populations
      identified by the climate envelope approach under both current and climate change
      scenarios. The URFs predict decreasing growth performance at low and middle
      elevations of the case study area, but increasing growth performance on high
      elevation sites. Our analysis suggests that population recommendations based on
      empirical approaches should be preferred and population selections by climate
      envelope models without considering climatic constrains of growth performance
      should be carefully appraised before transferring populations to planting
      locations with novel or dissimilar climate. 

PMID- 26288362
TI  - Regulation of the Contribution of Integrin to Cell Attachment on Poly(2
      Methoxyethyl Acrylate) (PMEA) Analogous Polymers for Attachment-Based Cell
      Enrichment.
AB  - Cell enrichment is currently in high demand in medical engineering. We have
      reported that non-blood cells can attach to a blood-compatible poly(2
      methoxyethyl acrylate) (PMEA) substrate through integrin-dependent and integrin
      independent mechanisms because the PMEA substrate suppresses protein adsorption.
      Therefore, we assumed that PMEA analogous polymers can change the contribution of
      integrin to cell attachment through the regulation of protein adsorption. In the
      present study, we investigated protein adsorption, cell attachment profiles, and
      attachment mechanisms on PMEA analogous polymer substrates. Additionally, we
      demonstrated the possibility of attachment-based cell enrichment on PMEA
      analogous polymer substrates. HT-1080 and MDA-MB-231 cells started to attach to
      poly(butyl acrylate) (PBA) and poly(tetrahydrofurfuryl acrylate) (PTHFA), on
      which proteins could adsorb well, within 1 h. HepG2 cells started to attach after
      1 h. HT-1080, MDA-MB-231, and HepG2 cells started to attach within 30 min to
      PMEA, poly(2-(2-methoxyethoxy) ethyl acrylate-co-butyl acrylate) (30:70 mol%,
      PMe2A) and poly(2-(2-methoxyethoxy) ethoxy ethyl acrylate-co-butyl acrylate)
      (30:70 mol%, PMe3A), which suppress protein adsorption. Moreover, the ratio of
      attached cells from a cell mixture can be changed on PMEA analogous polymers.
      These findings suggested that PMEA analogous polymers can be used for attachment
      based cell enrichment. 

PMID- 26288364
TI  - Secreted Frizzled Related Protein 3 in Chronic Heart Failure: Analysis from the
      Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA).
AB  - BACKGROUND: We have previously demonstrated an association between increased
      sFRP3 expression and adverse outcome in a population of HF irrespective of cause
      and left ventricular ejection fraction. In this study we evaluated the prognostic
      value of sFRP3 in older patients with chronic systolic HF of ischemic origin.
      METHODS: We evaluated sFRP3, by tertiles, as a risk factor for the primary
      endpoint (cardiovascular [CV] mortality, nonfatal myocardial infarction, nonfatal
      stroke), all-cause mortality, CV mortality, death from worsening HF (WHF), any
      coronary event, including sudden death, as well as hospitalizations for CV causes
      and WHF in 1444 patients from the CORONA population, randomly assigned to 10 mg
      rosuvastatin or placebo. RESULTS: Kaplan-Meier curves for the primary endpoint,
      as well as all-cause- and CV mortality revealed a markedly better survival for
      patients with sFRP3 levels in the middle tertile of compared to the 1st and 3rd
      tertile. In multivariable Cox-regression, after full adjustment including high
      sensitive CRP and NT-proBNP, a lower event rate for the primary end point, all
      cause and CV mortality was observed for patients with tertile 2 sFRP3 levels (HR
      0.57 [0.44-0.74], 0.55 [0.44-0.74] and 0.52 [0.39-0.69]; p<0.001), as well as for
      the number of coronary events (HR 0.62 [0.47-0.82], p = 0.001) and sudden death
      (HR 0.55 [0.37-0.82], p = 0.002). Applying sFRP3 values to the fully adjusted
      regression model resulted in highly significant continuous net reclassification
      improvements for the primary endpoint, all cause and CV mortality, coronary
      events and sudden death (range 0.24-0.31; p<=0.002 for all). CONCLUSIONS:
      Intermediate serum sFRP3 levels are associated with better survival and fewer CV
      events than low or high sFRP3 levels, independently of conventional risk factors,
      in older patients with chronic systolic HF of ischemic origin. Our study suggests
      that balanced Wnt activity might confer protective effects in a clinical HF
      setting. TRIAL REGISTRATION: http://www.clinicaltrials.gov NCT00206310.

PMID- 26288366
TI  - Modification of Kraft Lignin to Expose Diazobenzene Groups: Toward pH- and Light
      Responsive Biobased Polymers.
AB  - A pH- and light-responsive polymer has been synthesized from softwood kraft
      lignin by a two-step strategy that aimed to incorporate diazobenzene groups.
      Initially, styrene oxide was reacted with the phenolic hydroxyl groups in lignin,
      to offer the attachment of benzene rings, thus creating unhindered reactive sites
      for further modifications. The use of advanced spectroscopic techniques ((1)H and
      (31)P NMR, UV and FTIR) demonstrated that the reaction was quantitative and
      selective toward the phenolic hydroxyl groups. In a second step, the newly
      incorporated benzene rings were reacted with a diazonium cation to form the
      target diazobenzene motif, whose formation was again thoroughly verified. As
      anticipated, the diazobenzene-containing kraft lignin derivatives showed a pH
      dependent color change in solution and light-responsive properties resulting from
      the cis-trans photoisomerization of the diazobenzene group. 

PMID- 26288367
TI  - Combined or Serial Liver and Lung Transplantation for Epithelioid
      Hemangioendothelioma: A Case Series.
AB  - Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor with variable
      biological and clinical behavior. There is increasing experience with liver
      transplantation (LiTx) for hepatic EHE, even in cases of extrahepatic disease
      localization. Until now, no cases of lung transplantation (LuTx) had been
      reported for pulmonary EHE. This report describes three cases of EHE with
      multifocal disease in patients who underwent either serial or combined LiTx and
      LuTx. 

PMID- 26288368
TI  - [Public Health as a Pathway towards Optimising Human Beings in Terms of Better
      Resilience? The Leopoldina Statement on Public Health in Germany].
AB  - The June 2015 political statement of the National Academy of Sciences Leopoldina
      on Public Health in Germany emphasizes the need to strengthen Public Health and
      Public Health research in Germany. The Leopoldina authors' discernable desire to
      take into consideration the largest possible number of aspects and disciplines
      related to Public Health, however, leads to an accumulation of concepts with
      little or no content or even contradictive statements. Besides highly welcome
      explanation, for instance on the relevance of social determinants, the policy
      statement one-sidedly argues in favour of promoting genomics and other "omics"
      technologies. Indeed, the Leopoldina paper overrates the relevance of this and
      other technological approaches within Public Health and focuses too much on
      biomedical solutions. The potential of such technologies in the context of the
      health-in-all-policies approach which Leopoldina asks for is rather limited,
      however, when it comes to creating healthy living conditions. Genetic and other
      innovative technologies of medical research are hardly able to improve these
      conditions; they can merely contribute to enhancing the resilience of human
      beings in view of the increasingly uncontrollable environmental conditions -
      rather than changing these conditions. 

PMID- 26288365
TI  - Partially Protective Immunity Induced by a 20 kDa Protein Secreted by Trichinella
      spiralis Stichocytes.
AB  - BACKGROUND: Trichinella spiralis infection induces protective immunity against re
      infection in animal models. Identification of the antigens eliciting acquired
      immunity during infection is important for vaccine development against
      Trichinella infection and immunodiagnosis. METHODS AND FINDINGS: The T. spiralis
      adult cDNA library was immunoscreened with sera from pigs experimentally infected
      with 20,000 infective T. spiralis larvae. Total 43 positive clones encoding for
      28 proteins were identified; one of the immunodominant proteins was 20 kDa Ts-ES
      1 secreted by Trichinella stichocytes and existing in the excretory/secretory
      (ES) products of T. spiralis adult and muscle larval worms. Ts-ES-1 contains 172
      amino acids with a typical signal peptide in the first 20 amino acids. The
      expression of Ts-ES-1 was detected in both the adult and muscle larval stages at
      the mRNA and protein expression levels. Mice immunized with recombinant Ts-ES-1
      (rTs-ES-1) formulated with ISA50v2 adjuvant exhibited a significant worm
      reduction in both the adult worm (27%) and muscle larvae burden (42.1%) after a
      challenge with T. spiralis compared to the adjuvant control group (p<0.01). The
      rTs-ES-1-induced protection was associated with a high level of specific anti-Ts
      ES-1 IgG antibodies and a Th1/Th2 mixed immune response. CONCLUSION: The newly
      identified rTs-ES-1 is an immunodominant protein secreted by Trichinella
      stichocytes during natural infection and enables to the induction of partial
      protective immunity in vaccinated mice against Trichinella infection. Therefore,
      rTs-ES-1 is a potential candidate for vaccine development against trichinellosis.

PMID- 26288369
TI  - A Hybrid DNA-Templated Gold Nanocluster For Enhanced Enzymatic Reduction of
      Oxygen.
AB  - We report the synthesis and characterization of a new DNA-templated gold
      nanocluster (AuNC) of ~1 nm in diameter and possessing ~7 Au atoms. When
      integrated with bilirubin oxidase (BOD) and single walled carbon nanotubes
      (SWNTs), the AuNC acts as an enhancer of electron transfer (ET) and lowers the
      overpotential of electrocatalytic oxygen reduction reaction (ORR) by ~15 mV as
      compared to the enzyme alone. In addition, the presence of AuNC causes
      significant enhancements in the electrocatalytic current densities at the
      electrode. Control experiments show that such enhancement of ORR by the AuNC is
      specific to nanoclusters and not to plasmonic gold particles. Rotating ring disk
      electrode (RRDE) measurements confirm 4e(-) reduction of O2 to H2O with minimal
      production of H2O2, suggesting that the presence of AuNC does not perturb the
      mechanism of ORR catalyzed by the enzyme. This unique role of the AuNC as
      enhancer of ET at the enzyme-electrode interface makes it a potential candidate
      for the development of cathodes in enzymatic fuel cells, which often suffer from
      poor electronic communication between the electrode surface and the enzyme active
      site. Finally, the AuNC displays phosphorescence with large Stokes shift and
      microsecond lifetime. 

PMID- 26288370
TI  - Correction: Effects of Tail Clipping on Larval Performance and Tail Regeneration
      Rates in the Near Eastern Fire Salamander, Salamandra infraimmaculata.

PMID- 26288371
TI  - Disease Risk & Landscape Attributes of Tick-Borne Borrelia Pathogens in the San
      Francisco Bay Area, California.
AB  - Habitat heterogeneity influences pathogen ecology by affecting vector abundance
      and the reservoir host communities. We investigated spatial patterns of disease
      risk for two human pathogens in the Borrelia genus-B. burgdorferi and B.
      miyamotoi-that are transmitted by the western black-legged tick, Ixodes
      pacificus. We collected ticks (349 nymphs, 273 adults) at 20 sites in the San
      Francisco Bay Area, California, USA. Tick abundance, pathogen prevalence and
      density of infected nymphs varied widely across sites and habitat type, though
      nymphal western black-legged ticks were more frequently found, and were more
      abundant in coast live oak forest and desert/semi-desert scrub (dominated by
      California sagebrush) habitats. We observed Borrelia infections in ticks at all
      sites where we able to collect >10 ticks. The recently recognized human pathogen,
      B. miyamotoi, was observed at a higher prevalence (13/349 nymphs = 3.7%, 95% CI =
      2.0-6.3; 5/273 adults = 1.8%, 95% CI = 0.6-4.2) than recent studies from nearby
      locations (Alameda County, east of the San Francisco Bay), demonstrating that
      tick-borne disease risk and ecology can vary substantially at small geographic
      scales, with consequences for public health and disease diagnosis. 

PMID- 26288373
TI  - Correction: Expression of Human Gaucher Disease Gene GBA Generates
      Neurodevelopmental Defects and ER Stress in Drosophila Eye.

PMID- 26288374
TI  - Gorham's disease of the proximal tibia successfully treated with local
      administration of OK-432, followed by reconstruction with distraction
      osteogenesis: a case report.
AB  - Gorham's disease (GD) is a rare and intractable disease characterized by marked
      progression of osteolysis associated with lymphangioma and/or hemangioma. Here,
      we describe a case of GD of the proximal tibia occurring in a 10-year-old boy.
      Although we could not correctly diagnose it at first, we finally diagnosed him as
      having GD. Progression of osteolysis of the tibia stopped 3 months after the
      local administration of OK-432. Thereafter, the huge bone defect with varus and
      extension deformity was reconstructed successfully by distraction osteogenesis
      using the Ilizarov method. The present case suggests that local administration of
      OK-432, followed by distraction osteogenesis is a treatment option for GD. 

PMID- 26288372
TI  - Metabolomic and Lipidomic Analysis of Serum Samples following Curcuma longa
      Extract Supplementation in High-Fructose and Saturated Fat Fed Rats.
AB  - We explored, using nuclear magnetic resonance (NMR) metabolomics and fatty acids
      profiling, the effects of a common nutritional complement, Curcuma longa, at a
      nutritionally relevant dose with human use, administered in conjunction with an
      unbalanced diet. Indeed, traditional food supplements have been long used to
      counter metabolic impairments induced by unbalanced diets. Here, rats were fed
      either a standard diet, a high level of fructose and saturated fatty acid (HFS)
      diet, a diet common to western countries and that certainly contributes to the
      epidemic of insulin resistance (IR) syndrome, or a HFS diet with a Curcuma longa
      extract (1% of curcuminoids in the extract) for ten weeks. Orthogonal projections
      to latent structures discriminant analysis (OPLS-DA) on the serum NMR profiles
      and fatty acid composition (determined by GC/MS) showed a clear discrimination
      between HFS groups and controls. This discrimination involved metabolites such as
      glucose, amino acids, pyruvate, creatine, phosphocholine/glycerophosphocholine,
      ketone bodies and glycoproteins as well as an increase of monounsaturated fatty
      acids (MUFAs) and a decrease of n-6 and n-3 polyunsaturated fatty acids (PUFAs).
      Although the administration of Curcuma longa did not prevent the observed
      increase of glucose, triglycerides, cholesterol and insulin levels,
      discriminating metabolites were observed between groups fed HFS alone or with
      addition of a Curcuma longa extract, namely some MUFA and n-3 PUFA,
      glycoproteins, glutamine, and methanol, suggesting that curcuminoids may act
      respectively on the fatty acid metabolism, the hexosamine biosynthesis pathway
      and alcohol oxidation. Curcuma longa extract supplementation appears to be
      beneficial in these metabolic pathways in rats. This metabolomic approach
      highlights important serum metabolites that could help in understanding further
      the metabolic mechanisms leading to IR. 

PMID- 26288375
TI  - Vascular evaluation after cervical hip fractures in children: a case series of
      eight children examined by scintigraphy after surgery for cervical hip fracture
      and evaluated for development of secondary radiological changes.
AB  - Femoral neck fractures in children and young adults are rare, but have a high
      risk of avascular necrosis (AVN) and subsequent gradual collapse of the femoral
      head. In 2006, we initiated the use of scintigraphy for the diagnosis of vascular
      impairment after a cervical fracture in children. In the present retrospective
      case study, we evaluated the effect of the remaining postoperative circulation in
      the femoral head after fracture in terms of the development of AVN and secondary
      degenerative changes of the hip joint. Eight children, four girls and four boys
      [mean age 11.5 years (7-16)], had been operated for a cervical or a basocervical
      hip fracture between 2006 and 2012. The femoral head circulation was evaluated
      postoperatively with scintigraphy and all children had been followed
      radiographically for a minimum of 1 year. The Ficat classification was used to
      stage the AVN and the Stulberg classification was used to stage the sphericity of
      the femoral head at follow-up. In two patients, the femoral head had normal
      circulation postoperatively and they also had normal radiographs at follow-up. In
      two patients, the entire femoral head was avascular postoperatively and at follow
      up, one patient had normal radiographs and one had both subchondral sclerosis and
      flattening. These two patients had been treated with bisphosphonates and
      prolonged non-weight-bearing. Four patients had postoperatively retained
      circulation in parts of the femoral head. Three of these four patients had normal
      radiographs at follow-up. Evaluation of the remaining circulation after surgery
      may help to predict the outcome and guide the postoperative regime in children
      with a femoral neck fracture. 

PMID- 26288376
TI  - Imidazoles from nitroallylic acetates and alpha-bromonitroalkenes with amidines:
      synthesis and trypanocidal activity studies.
AB  - Cascade reactions of amidines with nitroallylic acetates and alpha
      bromonitroalkenes provide potentially bioactive imidazoles in good to excellent
      yields in most cases. While 2,4-disubstituted imidazol-5-yl acetates are formed
      in the first case, 2,4-disubstituted imidazoles, bearing no substituent at
      position 5, are the products in the second case. These two series of imidazoles,
      viz. 2,4,5-trisubstituted and 2,4-disubstituted, were screened for their activity
      against the protozoan parasite Trypanosoma cruzi which is responsible for Chagas
      disease. As many as three compounds were as active as the standard benznidazole
      and two others were 2-3-fold more active highlighting the potential of
      substituted imidazoles, easily accessible from nitroalkenes, as possible anti
      parasitic agents. 

PMID- 26288378
TI  - Targeted Magnetic Nanoparticles for Remote Magnetothermal Disruption of Amyloid
      beta Aggregates.
AB  - Remotely triggered hysteretic heat dissipation by magnetic nanoparticles (MNPs)
      selectively attached to targeted proteins can be used to break up self-assembled
      aggregates. This magnetothermal approach is applied to the amyloid-beta (Abeta)
      protein, which forms dense, insoluble plaques characteristic of Alzheimer's
      disease. Specific targeting of dilute MNPs to Abeta aggregates is confirmed via
      transmission electron microscopy (TEM) and is found to be consistent with a
      statistical model of MNP distribution on the Abeta substrates. MNP composition
      and size are selected to achieve efficient hysteretic power dissipation at
      physiologically safe alternating magnetic field (AMF) conditions. Dynamic light
      scattering, fluorescence spectroscopy, and TEM are used to characterize the
      morphology and size distribution of aggregates before and after exposure to AMF.
      A dramatic reduction in aggregate size from microns to tens of nanometers is
      observed, suggesting that exposure to an AMF effectively destabilizes Abeta
      deposits decorated with targeted MNPs. Experiments in primary hippocampal
      neuronal cultures indicate that the magnetothermal disruption of aggregates
      reduces Abeta cytotoxicity, which may enable future applications of this approach
      for studies of protein disaggregation in physiological environments.

PMID- 26288377
TI  - Macrophage cell death and transcriptional response are actively triggered by the
      fungal virulence factor Cbp1 during H. capsulatum infection.
AB  - Microbial pathogens induce or inhibit death of host cells during infection, with
      significant consequences for virulence and disease progression. Death of an
      infected host cell can either facilitate release and dissemination of
      intracellular pathogens or promote pathogen clearance. Histoplasma capsulatum is
      an intracellular fungal pathogen that replicates robustly within macrophages and
      triggers macrophage lysis by unknown means. To identify H. capsulatum effectors
      of macrophage lysis, we performed a genetic screen and discovered three mutants
      that grew to wild-type levels within macrophages but failed to elicit host-cell
      death. Each mutant was defective in production of the previously identified
      secreted protein Cbp1 (calcium-binding protein 1), whose role in intracellular
      growth had not been fully investigated. We found that Cbp1 was dispensable for
      high levels of intracellular growth but required to elicit a unique
      transcriptional signature in macrophages, including genes whose induction was
      previously associated with endoplasmic reticulum stress and host-cell death.
      Additionally, Cbp1 was required for activation of cell-death caspases-3/7, and
      macrophage death during H. capsulatum infection was dependent on the pro
      apoptotic proteins Bax and Bak. Taken together, these findings strongly suggest
      that the ability of Cbp1 to actively program host-cell death is an essential step
      in H. capsulatum pathogenesis. 

PMID- 26288379
TI  - What is your diagnosis? Cutaneous mass in a dog.

PMID- 26288381
TI  - Correction: Blue Marble Health Redux: Neglected Tropical Diseases and Human
      Development in the Group of 20 (G20) Nations and Nigeria.

PMID- 26288380
TI  - Altered prefrontal activity and connectivity predict different cognitive deficits
      in schizophrenia.
AB  - BACKGROUND: Cognitive dysfunction is considered a core feature of schizophrenia,
      and impaired performances in episodic memory (EM) and executive function (EF)
      tasks are consistently reported in schizophrenia patients. Traditional fMRI and
      EEG studies have helped identifying brain areas, including the prefrontal cortex
      (PFC), involved in these tasks. However, it is unclear whether intrinsic defects
      in prefrontal function per se contribute to poor performance in schizophrenia,
      given the presence of confounds like reduced motivation and psychotic symptoms.
      TMS/hd-EEG measurements are obtained without cognitive effort, and can be
      calculated in any cortical area. METHODS: We performed TMS/hd-EEG recordings in
      parietal, motor, premotor, and PFC in healthy individuals (N=20) and
      schizophrenia patients (N=20). Source modeling of TMS-evoked responses was
      performed, and measures of cortical activity (significant current density, SCD)
      and connectivity (significant current scattering, SCS) were computed. Patients
      with schizophrenia also performed Penn Word memory delayed (CPWd) and Penn
      Conditional Exclusion Test (PCET). CPWd evaluates EM and involves primarily PFC,
      whereas PCET reflects EF and implicates PFC with other brain regions. FINDINGS:
      We found no difference in SCD and SCS after TMS of parietal/motor cortices,
      whereas those parameters were reduced in premotor/prefrontal areas in
      schizophrenia patients. In PFC, where these measures were most defective, SCD was
      negatively correlated with performance in CPWd whereas higher SCS values were
      associated with more errors in PCET. CONCLUSION: These findings indicate that
      schizophrenia patients have intrinsic defects in both activity and connectivity
      of PFC, and that these defects are specifically associated with impairments in
      cognitive abilities.

PMID- 26288382
TI  - Variation in the Cost of Generic Topical Corticosteroids.

PMID- 26288384
TI  - EPR/ENDOR and Computational Study of Outer Sphere Interactions in Copper
      Complexes of Phenolic Oximes.
AB  - Copper complexes of the phenolic oxime family of ligands (3-X-salicylaldoximes)
      are used extensively as metal solvent extractants. Incorporation of
      electronegative substituents in the 3-position, ortho to the phenol group, can be
      used to buttress the interligand H-bonding, leading to an enhancement in
      extractant strength. However, investigation of the relevant H-bonding in these
      complexes can be exceedingly difficult. Here, we have combined EPR, ENDOR, DFT,
      and X-ray crystallography to study this effect. Analysis of the (1)H ENDOR data
      revealed a variation in the Cu...H(16) (oxime proton) distance from 2.92 A for
      the unsubstituted complex [Cu(L(2))2] to 3.65 A for the X = CH2N(C6H13)2
      substituted complex [Cu(L(3))2]. DFT calculations showed that this variation is
      caused by changes to the length and strength of the H-bond between the oximic
      hydrogen and the phenolate oxygen. Noticeable changes to the Cu...H(15)
      (azomethine proton) distances and the Cu...N bonding parameters were also
      observed in the two complexes, as revealed through the (N)A and (N)Q ENDOR data.
      Distortions in the structure of the complex and variations in the oximic proton
      to phenolate oxygen H-bond strength caused by the substituent (X) were confirmed
      by DFT and X-ray crystallography. DFT directly evidenced the importance of the
      interaction between H(16) and the amine nitrogen of CH2N(C6H13)2 in the
      buttressed complex and indicated that the high strength of this interaction may
      not necessarily lead to an enhancement of copper extraction, as it can impose an
      unfavorable geometry in the inner coordination sphere of the complex. Therefore,
      ENDOR, DFT, and X-ray structural data all indicate that the aminomethyl
      substituent (X) ortho to the phenolic oxygen atom provides a particularly strong
      buttressing of interligand H-bonding in these copper complexes and that these
      outer sphere interactions can significantly influence structure and stability. 

PMID- 26288383
TI  - Correlates to seroprevalent herpes simplex virus type 2 among rural Appalachian
      drug users.
AB  - Herpes simplex virus type 2 (HSV-2) is the most common cause of genital ulcer
      disease and, along with substance abuse, an important HIV risk factor. Therefore,
      the purpose of this study was to examine HSV-2 seroprevalence in a sample of drug
      users in rural Appalachia. Rural Appalachian individuals age 18 or older
      reporting non-medical use of prescription opioids, heroin, crack/cocaine, or
      methamphetamine in the past 6 months (n = 499) were included. Behavioral,
      demographic, and sexual network data were collected using interviewer
      administered questionnaires. Participants' serum was tested for HSV-2 antibodies
      using the Biokit rapid test (Lexington, MA). The estimated population
      seroprevalence of HSV-2 was 14.4% (95%CI: 9.6-19.4%). Only 8.8% were aware of
      being HSV-2+, and unprotected sex was reported in 80% of serodiscordant sexual
      relationships. In a multivariate model, female gender, age, older age at first
      oral sex, and frequency of unprotected sex in the sexual network were
      independently associated with HSV-2 seropositivity. Despite lower seroprevalence
      than that reported in similar studies of substance abusers, targeted
      interventions to reduce sexual risk behavior are warranted in this underserved
      population. Network-informed approaches with particular focus on women, older
      individuals, and those engaging in frequent unprotected sex are recommended.

PMID- 26288385
TI  - Enhancing the Photovoltaic Performance by Tuning the Morphology of Polymer:PC71BM
      Blends with a Commercially Available Nucleating Agent.
AB  - The use of a commercially available nucleating agent as the additive for the
      fabrication of polymer:PC71BM-based active layers by solution-processing can
      greatly enhance the power conversion efficiency (PCE) of bulk heterojunction
      polymer solar cells (BHJ PSCs). The enhancement of device performance is mainly
      due to the addition of nucleating agent, which is able to regulate the drying
      process of the active layer and decrease the oversized domain size of conjugated
      polymers. Via this effective strategy to optimize the film morphology, the
      designed device exhibits an enhancement as great as 30.8%. 

PMID- 26288386
TI  - Biodegradation and Toxicity of Protease/Redox/pH Stimuli-Responsive PEGlated PMAA
      Nanohydrogels for Targeting Drug delivery.
AB  - The application of nanomaterials in intelligent drug delivery is developing
      rapidly for treatment of cancers. In this paper, we fabricated a new kind of
      protease/redox/pH stimuli-responsive biodegradable nanohydrogels with methacrylic
      acid (MAA) as the monomer and N,N-bis(acryloyl)cystamine (BACy) as the cross
      linker through a facile reflux-precipitation polymerization. After that, the
      polyethylene glycol (PEG) and folic acid (FA) were covalently grafted onto the
      surface of the nanohydrogels for enhancement of their long in vivo circulation
      lifetime and active targeting ability to the tumor cells and tissues. This kind
      of nanohydrogels could be disassembled into short polymer chains (Mn<1140;
      PDI<1.35) both in response to glutathione (GSH) through reduction of the
      sensitive disulfide bonds and protease by breakage of the amido bonds in the
      cross-linked networks. The nanohydrogels were utilized to simultaneously load
      both hydrophilic drug doxorubicin (DOX) and hydrophobic drug paclitaxel (PTX)
      with high drug loading efficiency. The cumulative release profile showed that the
      drug release from the drug-loaded nanohydrogels was significantly expedited by
      weak acidic (pH 5.0) and reducing environment (GSH), which exhibited an distinct
      redox/pH dual stimuli-responsive drug release to reduce the leakage of drugs
      before they reach tumor site. In addition, the in vitro experiment results
      indicated that the multidrug-loaded system had synergistic effect on cancer
      therapy. Meanwhile, the acute toxicity and intravital fluorescence imaging
      studies were adopted to evaluate the biocompatibility and biotoxicity of the
      nanohydrogels, the experimental results showed that the PEG modification could
      greatly enhance the long in vivo circulation lifetime and reduce the acute
      toxicity (LD50: from 138.4 mg/kg to 499.7 mg/kg) of the nanohydrogels.

PMID- 26288387
TI  - Influence of fixed orthodontic treatment on the menstrual cycle of adult females:
      A prospective longitudinal study.
AB  - OBJECTIVE: To investigate the influence of fixed orthodontic treatment on the
      menstrual cycle, including menstrual cycle length (MCL) and duration of menstrual
      bleeding (DMB), in adult female patients. MATERIALS AND METHODS: This was a
      prospective longitudinal study conducted in Chengdu, China. A total of 164 adult
      women with normal menstrual cycles were recruited in the study, with 79 patients
      undergoing orthodontic treatment and 85 serving as controls. Data of MCL, DMB,
      and accompanying symptoms were collected over six consecutive menstrual cycles in
      each participant. Student's t test, Chi-square test, Moses extreme reaction test,
      and repeated measures analysis of variance were used for statistical analysis.
      RESULTS: The MCL of the first menstrual cycle (T1) was significantly elongated by
      2.1 +/- 0.5 days compared with baseline (P  =  .003, 95% CI [-3.7, -0.5]).
      Variability of MCL of the orthodontic group at T1 was also significantly greater
      (range, 15-46 days) than that of the control group (range, 24-36 days) (P < .05).
      No significant difference in MCL was found in the subsequent five menstrual
      cycles (T2-T6) compared with baseline, and no significant differences in DMB or
      other accompanying symptoms were observed throughout the study. CONCLUSION: Fixed
      orthodontic treatment may influence the MCL of adult females in the first month
      after bonding, but showed no effect on DMB or subsequent MCL through the follow
      ups.

PMID- 26288388
TI  - Clinician Perception of the Effectiveness of an Automated Early Warning and
      Response System for Sepsis in an Academic Medical Center.
AB  - RATIONALE: We implemented an electronic early warning and response system (EWRS)
      to improve detection of and response to severe sepsis. Sustainability of such a
      system requires stakeholder acceptance. We hypothesized that clinicians receiving
      such alerts perceive them to be useful and effective. OBJECTIVES: To survey
      clinicians after EWRS notification about perceptions of the system. METHODS: For
      a 6-week study period 1 month after EWRS implementation in a large tertiary
      referral medical center, bedside clinicians, including providers (physicians,
      advanced practice providers) and registered nurses (RNs), were surveyed
      confidentially within 2 hours of an alert. MEASUREMENTS AND MAIN RESULTS: For the
      247 alerts that triggered, 127 providers (51%) and 105 RNs (43%) completed the
      survey. Clinicians perceived most patients as stable before and after the alert.
      Approximately half (39% providers, 48% RNs) felt the alert provided new
      information, and about half (44% providers, 56% RNs) reported changes in
      management as a result of the alert, including closer monitoring and additional
      interventions. Over half (54% providers, 65% RNs) felt the alert was
      appropriately timed. Approximately one-third found the alert helpful (33%
      providers, 40% RNs) and fewer felt it improved patient care (24% providers, 35%
      RNs). CONCLUSIONS: A minority of responders perceived the EWRS to be useful,
      likely related to the perception that most patients identified were stable.
      However, management was altered half the time after an alert. These results
      suggest further improvements to the system are needed to enhance clinician
      perception of the system's utility.

PMID- 26288389
TI  - Sensitivity, Specificity, and Positivity Predictors of the Pneumococcal Urinary
      Antigen Test in Community-Acquired Pneumonia.
AB  - RATIONALE: Detection of the C-polysaccharide of Streptococcus pneumoniae in urine
      by an immune-chromatographic test is increasingly used to evaluate patients with
      community-acquired pneumonia. OBJECTIVES: We assessed the sensitivity and
      specificity of this test in the largest series of cases to date and used logistic
      regression models to determine predictors of positivity in patients hospitalized
      with community-acquired pneumonia. METHODS: We performed a multicenter,
      prospective, observational study of 4,374 patients hospitalized with community
      acquired pneumonia. MEASUREMENTS AND MAIN RESULTS: The urinary antigen test was
      done in 3,874 cases. Pneumococcal infection was diagnosed in 916 cases (21%); 653
      (71%) of these cases were diagnosed exclusively by the urinary antigen test.
      Sensitivity and specificity were 60 and 99.7%, respectively. Predictors of
      urinary antigen positivity were female sex; heart rate>=125 bpm, systolic blood
      pressure<90 mm Hg, and SaO2<90%; absence of antibiotic treatment; pleuritic chest
      pain; chills; pleural effusion; and blood urea nitrogen>=30 mg/dl. With at least
      six of all these predictors present, the probability of positivity was 52%. With
      only one factor present, the probability was only 12%. CONCLUSIONS: The urinary
      antigen test is a method with good sensitivity and excellent specificity in
      diagnosing pneumococcal pneumonia, and its use greatly increased the recognition
      of community-acquired pneumonia due to S. pneumoniae. With a specificity of
      99.7%, this test could be used to direct simplified antibiotic therapy, thereby
      avoiding excess costs and risk for bacterial resistance that result from broad
      spectrum antibiotics. We also identified predictors of positivity that could
      increase suspicion for pneumococcal infection or avoid the unnecessary use of
      this test.

PMID- 26288392
TI  - Potential ergogenic activity of grape juice in runners.
AB  - Recent studies have indicated that certain food products have ergogenic potential
      similar to that of sports supplements. The present study aimed to investigate the
      potential ergogenic effect of integral purple grape juice on the performance of
      recreational runners. Twenty-eight volunteers of both sexes (age, 39.8 +/- 8.5
      years; peak oxygen consumption, 43.2 +/- 8.5 mL/(kg.min)) were randomized into
      either a group that received grape juice (grape juice group (GJG), n = 15; 10
      mL/(kg.min) for 28 days) or a group that received an isocaloric, isoglycemic, and
      isovolumetric control beverage (control group (CG), n = 13). A time-to-exhaustion
      exercise test, anaerobic threshold test, and aerobic capacity test were
      performed, together with assessments of markers of oxidative stress,
      inflammation, immune response, and muscle injury, performed at baseline and 48 h
      after the supplementation protocol. The GJG showed a significant increase (15.3%)
      in running time-to-exhaustion (p = 0.002) without significant improvements in
      either anaerobic threshold (3.6%; p = 0.511) or aerobic capacity (2.2%; p =
      0.605). In addition, GJG exhibited significant increases in total antioxidant
      capacity (38.7%; p = 0.009), vitamin A (11.8%; p = 0.016), and uric acid (28.2%;
      p = 0.005), whereas alpha-1-acid glycoprotein significantly decreased (20.2%; p =
      0.006) and high-sensitivity C-reactive protein levels remained unchanged. In
      contrast, no significant changes occurred in any of these variables in the CG. In
      conclusion, supplementation with purple grape juice shows an ergogenic effect in
      recreational runners by promoting increased time-to-exhaustion, accompanied by
      increased antioxidant activity and a possible reduction in inflammatory markers. 

PMID- 26288393
TI  - Depleted iron stores and iron deficiency anemia associated with reduced ferritin
      and hepcidin and elevated soluble transferrin receptors in a multiethnic group of
      preschool-age children.
AB  - Iron deficiency anemia is prevalent in subgroups of the Canadian population. The
      objective of this study was to examine iron status and anemia in preschool-age
      children. Healthy children (n = 430, 2-5 years old, Montreal, Quebec, Canada)
      were sampled from randomly selected daycares. Anthropometry, demographics, and
      diet were assessed. Biochemistry included hemoglobin, ferritin, soluble
      transferrin receptors (sTfR), ferritin index, markers of inflammation (C-reactive
      protein, interleukin 6 (IL-6), and tumour necrosis factor alpha (TNFalpha)), and
      hepcidin. Iron deficiency and anemia cutoffs conformed to the World Health
      Organization criteria. Differences among categories were tested using mixed-model
      ANOVA or chi(2) tests. Children were 3.8 +/- 1.0 years of age, with a body mass
      index z score of 0.48 +/- 0.97, and 51% were white. Adjusted intakes of iron
      indicated <1% were at risk for deficiency. Hemoglobin was higher in white
      children, whereas ferritin was higher with greater age and female sex.
      Inflammatory markers and hepcidin did not vary with any demographic variable. The
      prevalence of iron deficiency was 16.5% (95% confidence interval (CI), 13.0
      20.0). Three percent (95% CI, 1.4-4.6) of children had iron deficiency anemia and
      12.8% (95% CI, 9.6-16.0) had unexplained anemia. Children with iron deficiency,
      with and without anemia, had lower plasma ferritin and hepcidin but higher sTfR,
      ferritin index, and IL-6, whereas those with unexplained anemia had elevated
      TNFalpha. We conclude that iron deficiency anemia is not very common in young
      children in Montreal. While iron deficiency without anemia is more common than
      iron deficiency with anemia, the correspondingly reduced circulating hepcidin
      would have enabled heightened absorption of dietary iron in support of
      erythropoiesis. 

PMID- 26288394
TI  - Regular- and postseason comparisons of playing time and measures of running
      performance in NCAA Division I women soccer players.
AB  - The management of playing time in National Collegiate Athletic Association (NCAA)
      soccer athletes may be a key factor affecting running performance during
      competition. This study compared playing time and running performance between
      regular-season and postseason competitions during a competitive women's soccer
      season. Nine NCAA Division I women soccer players (age, 21.3 +/- 0.9 years;
      height, 170.3 +/- 5.7 cm; body mass, 64.0 +/- 5.8 kg) were tracked using portable
      GPS devices across 21 games during a competitive season (regular season (n = 17);
      postseason (n = 4)). Movements on the field were divided into operationally
      distinct thresholds defined as standing/transient motion, walking, jogging, low
      speed running, moderate-speed running, high-speed running, sprinting, low
      intensity running, and high-intensity running. A significant increase in minutes
      played (+17%, p = 0.010) was observed at postseason compared with the regular
      season. Concomitant increases in time spent engaged in low-intensity running
      (LIR: +18%, p = 0.011), standing/transient motion (+35%, p = 0.004), walking
      (+17%, p = 0.022), distance covered while walking (+14%, p = 0.036), and at low
      intensity (+11%, p = 0.048) were observed. Performance comparisons between the
      first and second half within games revealed a significant decrease (p <= 0.05) in
      high-speed and high-intensity runs during the second half of the postseason
      compared with the regular season. Changes in minutes played correlated
      significantly with changes in absolute time spent engaged in LIR (r = 0.999, p <
      0.001), standing/transient motion (r = 0.791, p = 0.011), walking (r = 0.975, p =
      0.001), jogging (r = 0.733, p = 0.025), distance covered while walking (r =
      0.898, p < 0.001) and low-intensity activity (r = 0.945, p < 0.001). Negative
      correlations were observed between minutes played and absolute time sprinting (r
      = -0.698, p = 0.037) and distance covered sprinting (r = -0.689, p = 0.040).
      Results indicate that additional minutes played during the postseason were
      primarily performed at lower intensity thresholds, suggesting running performance
      during postseason competitions may be compromised with greater playing time in
      intercollegiate women's soccer. 

PMID- 26288395
TI  - Maximal power output during incremental cycling test is dependent on the
      curvature constant of the power-time relationship.
AB  - The aim of this study was to investigate whether the maximal power output (Pmax)
      during an incremental test was dependent on the curvature constant (W') of the
      power-time relationship. Thirty healthy male subjects (maximal oxygen uptake =
      3.58 +/- 0.40 L.min(-1)) performed a ramp incremental cycling test to determine
      the maximal oxygen uptake and Pmax, and 4 constant work rate tests to exhaustion
      to estimate 2 parameters from the modeling of the power-time relationship (i.e.,
      critical power (CP) and W'). Afterwards, the participants were ranked according
      to their magnitude of W'. The median third was excluded to form a high W' group
      (HIGH, n = 10), and a low W' group (LOW, n = 10). Maximal oxygen uptake (3.84 +/-
      0.50 vs. 3.49 +/- 0.37 L.min(-1)) and CP (213 +/- 22 vs. 200 +/- 29 W) were not
      significantly different between HIGH and LOW, respectively. However, Pmax was
      significantly greater for the HIGH (337 +/- 23 W) than for the LOW (299 +/- 40
      W). Thus, in physically active individuals with similar aerobic parameters, W'
      influences the Pmax during incremental testing. 

PMID- 26288396
TI  - New Markers for Separating Benign From Malignant Mesothelial Proliferations: Are
      We There Yet?
AB  - CONTEXT: The separation of benign from malignant mesothelial proliferations is
      crucial to patient care but is frequently morphologically difficult. OBJECTIVE:
      To briefly review adjunctive tests claimed to be useful in this setting and to
      examine in detail 2 new tests: p16 fluorescence in situ hybridization (FISH) and
      BRCA1-associated protein 1 (BAP1) immunohistochemistry. DESIGN: Literature review
      with emphasis on p16 FISH and BAP1 immunohistochemistry. RESULTS: Glucose
      transporter-1, p53, insulin-like growth factor 2 messenger RNA-binding protein 3
      (IMP-3), desmin, and epithelial membrane antigen have all been claimed to mark
      either benign or malignant mesothelial processes, but in practice they at best
      provide statistical differences in large series of cases, without being useful in
      an individual case. Homozygous deletion of p16 by FISH or loss of BAP1 has only
      been reported in malignant mesotheliomas and not in benign mesothelial
      proliferations. BAP1 appears to be lost more frequently in epithelial than mixed
      or sarcomatous mesotheliomas. Homozygous deletion of p16 by FISH is seen in
      pleural epithelial, mixed, and sarcomatous mesotheliomas, but it is much less
      frequent in peritoneal mesothelioma. The major drawback to both these tests is
      limited sensitivity; moreover, failure to find p16 deletion or BAP1 loss does not
      make a mesothelial process benign. CONCLUSIONS: In the context of a mesothelial
      proliferation, the finding of homozygous deletion of p16 by FISH or loss of BAP1
      by immunohistochemistry is, thus far, 100% specific for malignant mesothelioma.
      The limited sensitivity of each test may be improved to some extent by running
      both tests.

PMID- 26288390
TI  - Early Childhood Risk Factors for Decreased FEV1 at Age Six to Seven Years in
      Young Children with Cystic Fibrosis.
AB  - RATIONALE: There are limited objective measures of the severity of lung disease
      before children are able to routinely perform spirometry, generally at age 6
      years. Identifying risk factors for reduced lung function at age 6 provides
      opportunities to intervene and slow the progression of cystic fibrosis (CF) lung
      disease. OBJECTIVES: To evaluate early childhood predictors of lung function at
      age 6-7 in a large U.S. CF cohort in the current era of widespread early
      eradication therapy for Pseudomonas aeruginosa (P. aeruginosa). METHODS:
      Participants were children with CF enrolled before age 4 in the Early Pseudomonas
      Infection Control (EPIC) Observational Study, a multicenter, longitudinal study
      that enrolled P. aeruginosa-negative children not exceeding 12 years of age.
      Linear regression was used to estimate the association between potential early
      childhood risk factors and the best FEV1% predicted at age 6-7 years.
      MEASUREMENTS AND MAIN RESULTS: Four hundred and eighty-four children (of 1,797
      enrolled in the EPIC Observational Study) met the eligibility criteria for this
      analysis. Mean (SD) age at enrollment was 2.0 (1.3) years. In a multivariable
      model adjusted for age at enrollment, the following risk factors were
      significantly associated with lower mean (95% confidence interval) FEV1%
      predicted at age 6-7: weight percentile less than 10% during the year of
      enrollment (-5.3 [-9.1, -1.5]), P. aeruginosa positive during the year of
      enrollment (-2.8 [-5.7, 0.0]), crackles or wheeze during the year of enrollment (
      5.7 [-9.4, -1.9]), mother's education of high school or less (-4.2 [-7.3, -1.2]),
      and mother smoked during pregnancy (-4.4 [-8.8, 0.1]). CONCLUSIONS: In this large
      U.S. cohort, we identified several early childhood risk factors for lower FEV1 at
      age 6-7 years, most of which are modifiable. Clinical trial registered with
      www.clinicaltrials.gov (NCT00097773).

PMID- 26288397
TI  - Transoral Robotic Surgery in Oropharyngeal Carcinoma.
AB  - CONTEXT: The incidence of oropharyngeal squamous cell carcinoma has increased
      during the past decade and is related primarily to the human papillomavirus. This
      change in etiology, from tobacco and alcohol to human papillomavirus, has
      resulted in improved survival for the disease. In the United States, open
      resection had largely been replaced by concurrent chemotherapy and/or
      radiotherapy by the early 2000s. The advent of transoral surgery has led to an
      increase in surgery as the primary treatment for both early- and advanced-stage
      oropharyngeal squamous cell carcinoma because it has potential advantages over
      open surgery and nonsurgical modalities. OBJECTIVE: To provide an overview of
      transoral robotic surgery for oropharyngeal squamous cell carcinoma and contrast
      it with other surgical and nonsurgical modalities. DATA SOURCES: Articles from
      2000 to 2014 were accessioned on PubMed and reviewed for utility by the primary
      authors. CONCLUSIONS: Transoral surgery has become more commonly used as a
      minimally invasive approach to treat oropharyngeal tumors. Other strategies,
      including radiation, chemotherapy with radiation, and open surgery, are still
      important treatment approaches. The treatment options for an individual patient
      rely on multiple factors, including the tumor location and size, features of the
      tumor, and patient comorbidities. The continued study of these techniques is
      important to match the patient with the most appropriate treatment.

PMID- 26288398
TI  - Atopic Dermatitis; Etio-Pathogenesis, An Overview.
AB  - Atopic dermatitis is a well-recognized clinical entity, several facets of which
      continue to be mystified. Accordingly, its etio-pathogenesis is largely elusive.
      It appears to be an outcome of interplay of several undertones, namely: genetics,
      maternal factor and inheritance, pregnancy/intrauterine, environmental factors,
      immune dysregulation, immuno-globulins, role of diet, and infection. Besides,
      recent innovative breakthroughs consisting of nutritional supplementation, the
      highlights of which were considered worthwhile to take stock of to define its
      current status. An endeavor to enlighten the audience has been made for their
      benefit. 

PMID- 26288400
TI  - A Novel Contrast Stain for the Rapid Diagnosis of Pityriasis Versicolor: A
      Comparison of Chicago Sky Blue 6B Stain, Potassium Hydroxide Mount and Culture.
AB  - BACKGROUND: The mycological study of pityriasis versicolor is usually done by
      potassium hydroxide (KOH) mount and culture. However, KOH mount lacks a color
      contrast and requires a trained eye to interpret, while culture is difficult to
      perform, time consuming and has low sensitivity. Chicago Sky Blue 6B (CSB) is a
      new contrast stain that highlights the fungal hyphae and spores, blue against a
      purplish background. AIMS AND OBJECTIVES: This study was done to compare the
      utility of a novel contrast stain (CSB stain) with KOH mount and culture.
      MATERIALS AND METHODS: Skin scrapings from the lesions of 100 clinically
      diagnosed cases of P. versicolor were subjected to (1) KOH mount and CSB stain
      for direct microscopic examination and (2) culture using Sabouraud's dextrose
      agar. The statistical analysis of CSB stain and culture was done using KOH mount
      as the reference method, as it is the most commonly performed and practical
      diagnostic test available for P. versicolor. An interrater reliability analysis
      using the Cohen's Kappa statistic was performed to determine consistency
      (agreement) among the different modalities. OBSERVATIONS AND RESULTS: Direct
      microscopy with CSB stain, KOH mount and mycological culture showed positive
      results in 98 (98%), 92 (92%) and 56 (56%) patients, respectively. Using KOH
      mount as the reference method, CSB stain had a sensitivity of 100% which was
      significantly higher than culture (60.9%). Statistically significant fair
      agreement was found between CSB stain and KOH mount (94% with kappa=0.38, P <
      0.001). Negligible agreement was found between CSB stain and culture (66%,
      kappa=0.199, P = 0.001) as well as between KOH mount and culture (64%,
      kappa=0.051, P = 0.107). CONCLUSION: CSB staining of skin scrapings is the most
      sensitive method for the diagnosis of pityriasis versicolor. Due to the distinct
      contrast provided by CSB, it is easy to perform, rapid and qualitatively superior
      to KOH mount.

PMID- 26288399
TI  - Malassezia-Can it be Ignored?
AB  - Genus Malassezia comprises of 14 species of "yeast like fungi," 13 of which are
      lipophilic and 1 is nonlipophilic. They are known commensals and in predisposed
      individuals they commonly cause a spectrum of chronic recurrent infections. They
      rarely also cause serious illnesses like catheter-related blood stream
      infections, CAPD associated peritonitis etc., Though these fungi have been known
      to man for over 150 years, their fastidious nature and cumbersome culture and
      speciation techniques have restricted research. Since the last taxonomic
      revision, seven new species have been added to this genus. Their ability to evade
      the host immune system and virulence has increased the spectrum of the diseases
      caused by them. These agents have been implicated as causal agents in common
      diseases like atopic dermatitis recently. Though culture-based research is
      difficult, the new molecular analysis techniques and facilities have increased
      research in this field such that we can devote more attention to this genus to
      study in detail, their characteristics and their growing implications
      implications in the clinical scenario. 

PMID- 26288401
TI  - Unique TTC Repeat Base Pair Loss Mutation In Cases of Pure Neural Leprosy: A
      Survival Strategy of Mycobacterium Leprae?
AB  - BACKGROUND: Genomic reduction helps obligate intracellular microbes to survive
      difficult host niches. Adaptation of Mycobacterium leprae in cases of pure neural
      leprosy (PNL) in the intracellular niche of peripheral nerves can be associated
      with some gene loss. Recently, a stable but variable number of tandem repefzats
      (TTC) have been reported in strains of M. leprae. FolP and rpoB genes are the two
      common mutation sites which deal with the susceptibility of the bacteria to
      drugs. AIM: We attempted to find if genomic reduction of M. leprae in context of
      these TTC repeats or mutations in folP1 and rpoB can be the reason for the
      restriction of M. leprae in the nerves in PNL. MATERIALS AND METHODS: DNA
      extracts taken from fine needle aspiration of affected nerves of 24 PNL cases
      were studied for tandem repeats with 21TTC primer in multiplex-PCR. Mutations
      were also studied by PCR Amplification of SRDR (Sulphone Resistance Determining
      Region) of the folP1 and multiple primer PCR amplification refractory mutation
      system (MARS) of the rpoB. RESULTS: Of the 24 PNL, only 1 patient showed mutation
      in the rpoB gene and none in the folp1 gene. Studying the mutation in TTC region
      of the M. leprae gene we found that all the cases have a loss of a few bases in
      the sequence. CONCLUSION: We can conclude that there is consistent loss in the
      bases in the TTC region in all cases of pure neural Hansen and we postulate that
      it may be an adaptive response of the bacteria to survive host niche resulting in
      its restriction to peripheral nerves.

PMID- 26288402
TI  - No Evidence of Human Papilloma Virus Infection in Basal Cell Carcinoma.
AB  - BACKGROUND: Basal cell carcinoma (BCC) is the most common skin cancer among
      whites, and several risk factors have been discussed in itsdevelopment and
      progress. Detection of human papilloma virus (HPV) deoxyribonucleic acid (DNA)
      BCCs in some studies suggests that the virus may play a role in the pathogenesis
      of this disease. Several molecular studies showed conflicting reports. AIMS: The
      purpose of this study was to investigate the association between HPV and BCC
      using polymerase chain reaction (PCR). MATERIALS AND METHODS: HPV DNA detection
      was done for 42 paraffin-embedded tissue specimens of BCC and 42 normal skin
      samples around the lesions by PCR using GP5+/GP6+ primers. RESULTS: HPV DNA was
      not found in any of the 42 samples of BCC, and only one normal skin sample around
      the lesions was positive for HPV DNA by PCR. CONCLUSION: In this study, no
      statistically significant difference was seen between the presence of HPV DNA in
      BCC and normal skin around the lesion, and HPV is not likely to have an important
      role in pathogenesis of BCC.

PMID- 26288403
TI  - Prolonged Remission of Psoriasis with Azathioprine Pulse Therapy.
AB  - BACKGROUND: Although various therapies used for the treatment of psoriasis are
      able to produce remission, yet relapses, a common problem, remains frequent. It
      was observed that treatment with intermittent high dose (IHD) and continuous low
      dose (CLD) azathioprine can produce prolonged and durable remission in psoriasis.
      AIMS: To see the long term effect of azathioprine pulse therapy (APT) in
      psoriasis. METHODS: Ten patients with psoriasis who has completed more than 5
      years in remission with azathioprine pulse therapy are being taken in the study.
      They were given IHD azathioprine (500 mg on 3 consecutive days which is repeated
      every month) with CLD azathioprine (100 mg orally) daily in between IHD. The
      entire treatment schedule was divided into four phases. During phase I, treatment
      with IHD and CLD azathioprine was started and continued till complete clearance
      of lesions after which, patients proceeded to Phase II. In phase II, they
      continued to get treatment with IHD and CLD. After continued remission for a
      period of nine months, they entered into phase III, when the treatment with IHD
      was stopped, but CLD continued. If there was no recurrence after nine months of
      phase III treatment, CLD was also withdrawn, and patients were followed-up
      without any treatment (Phase IV). RESULTS: All 10 patients completed treatment
      and are in remission for more than five years without any treatment. CONCLUSIONS:
      Out of 60 patients in phase IV, 10 patients were in continuous remission for more
      than five years, after all treatment had been stopped. Thus, azathioprine pulse
      therapy regimen produces prolonged remission in psoriasis.

PMID- 26288404
TI  - Repigmentation of Hypopigmented Scars Using Combination of Fractionated Carbon
      Dioxide Laser with Topical Latanoprost Vs. Fractionated Carbon Dioxide Laser
      Alone.
AB  - BACKGROUND: Fractionated carbon dioxide (CO2) can treat hypopigmented scars.
      Latanoprost is a prostaglandin analog used to treat glaucoma. It can cause
      adverse effects, such as periocular hyperpigmentation. The aim of this study was
      to assess the efficacy and safety of latanoprost plus CO2 laser on the
      repigmentation of hypopigmented scars. PATIENTS AND METHODS: 28 patients with
      hypopigmented scars were divided randomly into two groups. The patients in group
      A were treated in six sessions (1-month intervals) with 10600-nm fractional CO2
      laser plus latanoprost 0.005% and those of group B fractionated CO2 laser plus
      placebo (distilled water). Digital photographs were taken at baseline and 3
      months after the last treatment session. The blinded dermatologist compared the
      photographs and evaluated the efficacy of treatment in the hypopigmented scars
      using a 4-scale point (grade 1-4). Patient satisfaction was scored from 0 to 10
      on a visual analog scale. RESULTS: Follow-up results 12 weeks after the last
      treatment session demonstrated that 11 of the 14 patients in group A had more
      than 50% improvement in hypopigmentation The difference in improvement of the two
      groups was statistically significant (P = 0.027). The mean of the VAS scores of
      patients in group A was 6.50 +/- 1.45 and in group B 4.57 +/- 1.6. The difference
      in mean satisfaction of the two groups was statistically significant (P = 0.003).
      Side effects were mild and resolved within 1 to 5 days. CONCLUSION: The
      fractional CO2 laser resurfacing plus topical latanoprost can be used as a safe
      and efficacious method to treat hypopigmented scars.

PMID- 26288391
TI  - Executive Function, Survival, and Hospitalization in Chronic Obstructive
      Pulmonary Disease. A Longitudinal Analysis of the National Emphysema Treatment
      Trial (NETT).
AB  - RATIONALE: Cognitive dysfunction has been demonstrated in chronic obstructive
      pulmonary disease (COPD), but studies are limited to cross-sectional analyses or
      incompletely characterized populations. OBJECTIVES: We examined longitudinal
      changes in sensitive measures of executive function in a well-characterized
      population of patients with severe COPD. METHODS: This study was performed on
      patients enrolled in the National Emphysema Treatment Trial. To assess executive
      function, we analyzed trail making (TM) A and B times at enrollment in the trial
      (2,128 patients), and at 12 (731 patients) and 24 months (593 patients) after
      enrollment, adjusted for surgery, marriage status, age, education, income,
      depression, PaO2, PaCO2, and smoking. Associations with survival and
      hospitalizations were examined using Cox regression and linear regression models.
      MEASUREMENTS AND MAIN RESULTS: The average age of the patients was 66.4 years,
      and the average FEV1 was 23.9% predicted. At the time of enrolment, 38% had
      executive dysfunction. Compared with those who did not, these patients were
      older, less educated, had higher oxygen use, higher PaCO2, worse quality of life
      as measured by the St. George's Respiratory Quotient, reduced well-being, and
      lower social function. There was no significant change over 2 years in TM A or B
      times after adjustment for covariables. Changes in TM B times were modestly
      associated with survival, but changes in TM B-A times were not. Changes in TM
      scores were not associated with frequency of hospitalization. Lung function,
      PaO2, smoking, survival, and hospitalizations were not significantly different in
      those with executive dysfunction. CONCLUSIONS: In this large population of
      patients with severe emphysema and heavy cigarette smoking exposure, there was no
      significant decline over 2 years in cognitive executive function as measured by
      TM tests. There was no association between executive function impairment and
      frequency of hospitalization, and there was a possible modest association with
      survival. It is plausible that cerebrovascular comorbidities explain previously
      described cognitive pathology in COPD.

PMID- 26288406
TI  - Primary Cutaneous CD8(+) CD30(+) Anaplastic Large Cell Lymphoma: An Unusual Case
      with a High Ki-67 index-A Short Review.
AB  - Primary cutaneous anaplastic large cell lymphoma (PCALCL) is a part of the
      spectrum of CD30(+) cutaneous lymphoproliferative disorder, characterized by
      variable degrees of CD2, CD3, CD4 and CD5 expression by lymphoid cells. PCALCLs
      with an expression of cytotoxic phenotype (CD8(+)) and cytotoxic proteins are
      uncommon. Cutaneous CD8(+) CD30(+) lymphoproliferative lesions are difficult to
      classify, diagnose and may be the cause of misdiagnose. CD8(+) PCALCL must be
      distinguished from CD8(+) mycosis fungoides, lymphomatoid papulosis type D and
      primary cutaneous aggressive epidermotropic CD8(+) T-cell lymphoma. Usually
      CD8(+) PCALCL is an indolent disease with a favorable prognosis, except few cases
      can show poor outcomes. The high Ki-67 index points toward advanced PCALCL.
      Treatment modalities include surgical excision, radiotherapy and clinical
      monitoring. Chemotherapy is reserved for disseminated disease. We report a 59
      year-old male presented with rapid development of multiple painful reddish-brown
      plaques and nodular ulcerative skin lesions over the left thigh region since 2
      months. A diagnosis of CD8(+) PCALCL with a high Ki-67 index was made on the
      basis of histology and immunohistochemistry, in co-relation with clinical
      presentation. 

PMID- 26288405
TI  - Long-Term Follow-up and Donor Site Changes Evaluation in Suction Blister
      Epidermal Grafting Done for Stable Vitiligo: A Retrospective Study.
AB  - BACKGROUND: Suction blister epidermal grafting (SBEG) is one of the most commonly
      performed types of vitiligo surgery for stable vitiligo. The advantages of SBEG
      include cost-effectiveness and a relatively easier learning curve for the
      surgeon. AIMS: To evaluate the outcome in terms of both recipient and donor site
      changes, on long-term follow-up of the patients who underwent SBEG in our center.
      METHODS: Thirty patients, 21 females and 9 males ages ranging from 9 to 55 years,
      all having either stable vitiligo not responding to medical line of treatment,
      were included in the study done which involved a variable follow-up period
      ranging from 2 to 62 months (mean 23.6, standard deviation 17.79). SBEG was done
      as day care procedure. The patients were reviewed after 1-week and thereafter
      followed-up in the subsequent months and years. The results of the procedures
      were graded as poor (0-24%), fair (24-64%), good (64-94) and excellent (95-100%)
      depending on the patient satisfaction. Donor site changes were also analyzed.
      RESULTS: The face and lips showed an excellent result and color match and
      persistent pigment retention. The larger areas, especially the lesions on the
      limbs showed comparatively less response. Of the total, 6.7% showed poor, 13.3%
      fair, 30% good and 50% excellent response to treatment. Patient satisfaction
      wise, 53.3% of the patients were very happy, 26.7% were happy, 10% satisfied and
      10% unhappy. Significant positive correlation between patient satisfaction and
      physician observation was seen (Spearman's rho 0.866). CONCLUSIONS: In spite of
      recent advances in surgical modalities like cellular grafting, SBEG continues to
      be a good, cost-effective, surgical method of treating vitiligo especially on the
      face and lip. The donor site also tends to show good healing tendency with
      minimal scarring and postinflammatory pigmentation.

PMID- 26288407
TI  - Eyelash Trichomegaly.
AB  - Eyelash trichomegaly is increased length, curling, pigmentation or thickness of
      eyelashes. Various causes include congenital syndromes, acquired conditions and
      drugs. It can manifest at birth or present later in life. It can form a part of
      spectrum of manifestations of some congenital syndromes. Although it tends to
      have a benign course, it can lead to psychological disturbances and can result in
      corneal abrasions and visual disturbances, if trichiasis occurs. This article
      focuses on its etiology, pathogenesis and brief management. 

PMID- 26288408
TI  - Omalizumab-A Review.
AB  - Omalizumab is a recombinant, humanized, monoclonal antibody against human
      immunoglobulin E (IgE). The US FDA has approved this molecule for chronic
      urticaria. 

PMID- 26288409
TI  - Amyloidosis Cutis Dyschromica: A Rare Reticulate Pigmentary Dermatosis.
AB  - We are reporting a rare case of amyloidosis cutis dyschromica in a 41-year-old
      man. This is a rare form of primary cutaneous amyloidosis characterized by
      reticulate pigmentation with hypopigmented and hyperpigmented macules, onset in
      childhood, familial tendency in some, occasional mild itching and deposition of
      amyloid in the papillary dermis. Our case also had multiple bilaterally
      symmetrical hyperpigmented keratotic papules abutting the axillary vault
      resembling those seen in Dowling-Deogs disease. The other unusual feature in this
      patient was the strong family history of vitiligo, which we are unable to
      explain. We have also tried to explain the mechanism leading to the
      hyperpigmentation and hypopigmentation in amyloidosis cutis dyschromica. 

PMID- 26288410
TI  - Progressive Nodular Histiocytosis Associated with Eale's Disease.
AB  - Progressive nodular histiocytosis (PNH) is a rare normolipemic macrophage
      disorder and belongs to a subgroup of non-Langerhans cell histiocytosis (LCHs)
      which is characterized by a progressive course with no sign of spontaneous
      resolution but without systemic involvement. We report a 30-year-old gentleman
      who presented with skin lesions all over the body associated with gradual
      bilateral painless loss of vision. On examination, approximately 30 to 40, skin
      colored, firm, non-tender papules and nodules were noted over the body especially
      on the face and trunk. A skin biopsy revealed a cellular tumor in the dermis
      composed of oval to spindle-shaped cells, positive for CD68 but negative for S
      100, CD34, CD21, CD35 and HMB45, supporting a diagnosis of spindle cell
      histiocytic tumor. Ophthalmic examination revealed a generalized arteriolar
      attenuation in both eyes. He received Tab Imatinib 400 mg OD for 5 months
      followed by Tab Pazopanib 800 mg OD for 4 months and both the drugs were stopped
      due to lack of any response in the skin lesions. We report this case due to its
      rarity, characteristic clinical presentation, and its association with Eale's
      disease. Primary treatment remains surgical excision of bothersome lesions and
      optimal systemic treatment is still unknown. 

PMID- 26288411
TI  - O'Brien Actinic Granuloma: A Case Report and Brief Review of Literature.
AB  - O'Brien first described the actinic granuloma in 1975, as an infrequent
      granulomatous disorder occurring in sun-exposed skin, with a slow but often self
      limited course. Ever since its initial description, the actinic physiopathogenic
      hypothesis has been debated by many authors. We report a 60-year-old female rural
      worker that presented with a 14 * 7 cm annular lesion with erythematous elevated
      borders and an atrophic center on the right calf. The lesion was evolving for 2
      years, and histopathology confirmed actinic granuloma. She started acitretin with
      halting of disease progression after 6 months of therapy. Our case can also be
      associated to actinic damage, despite its unusual location, therefore
      highlighting the role of solar elastosis in the development of O'Brien actinic
      granuloma. 

PMID- 26288412
TI  - Trichoepithelioma and Basal Cell Carcinoma with Squamous Differentiation: Is it
      Causal or Coincidental?
AB  - Trichoepitheliomas (TEs) are benign cutaneous tumors that occur either as
      solitary non-familial or multiple familial. We report a case of multiple familial
      trichoepithelioma (MFT) in a 55-year-old female patient and her son who came with
      complaints of single ulcerated mass involving the left nasolabial fold and cheek.
      She had multiple papules and nodules all over the face and neck since 25 years.
      Histopathological examination of an ulcerated lesion revealed features of basal
      cell carcinoma (BCC) with squamous differentiation, which was confirmed by
      immunohistochemistry. A skin biopsy obtained from the papule on neck showed
      features of TE. However, whether BCC developed independently or by transformation
      from TE was uncertain. Her 36-year-old son presented with similar lesions on the
      face and a skin biopsy showed features of TE. Though malignant transformation of
      TE is quite rare, awareness of the potential for evolution of carcinoma in
      patients with MFT is important for management of these patients. 

PMID- 26288414
TI  - A Tale of Two Tails: Not Just Skin Deep.
AB  - The dorsal cutaneous appendage or the so called human tail is a rare congenital
      anomaly protruding from the lumbo-sacro-coccygeal area. These caudal appendages
      are divided into true-tails and pseudo-tails. We report here two cases of
      congenital pseudo-tail with underlying spina bifida and lipo-meningocele. In this
      article we seek to emphasize that, as the skin and nervous systems are intimately
      linked by their similar ectodermal origin, a dorsal appendage may be regarded as
      a cutaneous marker of the underlying spinal dysraphism. 

PMID- 26288413
TI  - Bilateral Systematized Epidermolytic Verrucous Epidermal Nevus: A Rare Entity.
AB  - Verrucous epidermal nevi are congenital, noninflammatory cutaneous hamartomas
      composed of keratinocytes. They follow the lines of Blaschko and show
      hyperkeratosis without cellular atypia. The routine histology shows variable
      amount of hyperkeratosis, acanthosis and papillomatosis and rarely epidermolytic
      hyperkeratosis. We saw a 3-year-old boy with bilaterally symmetrical,
      systematized verrucous plaques along the lines of Blaschko extensively involving
      the trunk and extremities but sparing the face and palmoplantar skin.
      Histopathology showed features of epidermal nevi with prominent epidermolytic
      hyperkeratosis. We report here the case for the rarity of this entity. 

PMID- 26288415
TI  - Reactive Eccrine Syringofibroadenomatosis Presenting as Bilateral Plantar
      Hyperkeratosis.
AB  - Eccrine syringofibroadenoma (ESFA) is a rare cutaneous tumor with eccrine
      differentiation with varied clinical manifestations. We report a case of reactive
      eccrine syringofibroadenomatosis associated with chronic bilateral plantar ulcers
      in a patient with diabetes mellitus presenting as plantar hyperkeratosis and
      verrucous growth at margins. 

PMID- 26288416
TI  - D-penicillamine Induced Degenerative Dermopathy.
AB  - D-penicillamine interferes with elastin and collagen metabolism and produces
      several cutaneous and multi-systemic side-effects. We present two cases of
      Wilson's disease who on long-term penicillamine therapy developed drug-induced
      degenerative dermopathy manifesting as skin fragility over pressure sites and
      cutis laxa-like changes. 

PMID- 26288417
TI  - Progressive Symmetric Erythrokeratoderma Having Overlapping Features With
      Erythrokeratoderma Variabilis and Lesional Hypertrichosis: Is Nomenclature
      "Erythrokeratoderma Variabilis Progressiva" More Appropriate?

PMID- 26288418
TI  - Imatinib-induced Transverse Melanonychia: An Unusual Presentation.

PMID- 26288419
TI  - Post Herpes Zoster Trigeminal Trophic Syndrome in a Child.

PMID- 26288420
TI  - A Baffling presentation of a greenish macule on the chest.

PMID- 26288421
TI  - Multiple Asymptomatic Papules on the Back of the Right Side of the Chest.

PMID- 26288422
TI  - Cultural Adaptation of the Cardiff Acne Disability Index to a Hindi Speaking
      Population: A Pilot Study.
AB  - BACKGROUND: Acne vulgaris is known to impair many aspects of the quality of life
      (QoL) of its patients. AIM: To translate the Cardiff Acne Disability Index (CADI)
      from English into Hindi and to assess its validity and reliability in Hindi
      speaking patients with acne from India. METHODS: Hindi version of CADI,
      translated and linguistically validated as per published international
      guidelines, along with a previously translated Hindi version of dermatology life
      quality index (DLQI) and a demographic questionnaire were administered to acne
      patients. The internal consistency reliability of the Hindi version of CADI and
      its concurrent validity were assessed by Cronbach's alpha co-efficient and
      Spearman's correlation co-efficient respectively. Construct validity was examined
      by factor analysis. Statistical analysis was carried out using the Statistical
      Package for the Social Sciences (SPSS) version 20 (SPSS Inc., Chicago, IL, USA)
      for Windows. RESULTS: One hundred Hindi speaking patients with various grades of
      acne participated in the study. Hindi version of CADI showed high internal
      consistency reliability (Cronbach's alpha co-efficient = 0.722). Mean item-to
      total correlation co-efficient ranged from 0.502 to 0.760. Concurrent validity of
      the scale was supported by a significant correlation with the Hindi DLQI. Factor
      analysis revealed the presence of two dimensions underlying the factor structure
      of the scale. CONCLUSION: Hindi CADI is equivalent to the original English
      version and constitutes a reliable and valid tool for clinical assessment of the
      impact of acne on QoL.

PMID- 26288423
TI  - Correlation of Skin Changes with Hormonal Changes in Polycystic Ovarian Syndrome:
      A Cross-sectional Study Clinical Study.
AB  - BACKGROUND: Polycystic ovarian syndrome (PCOS) is a heterogenous collection of
      signs and symptoms that when gathered, form a spectrum of disorder with
      disturbance of reproductive, endocrine and metabolic functions. AIM: The aim of
      this study is to correlate the skin manifestations with hormonal changes and to
      know the incidence and prevalence of skin manifestations in patients with PCOS.
      MATERIALS AND METHODS: A total of 40 patients with PCOS were examined during 1
      year time period from May 2008 P to May 2009. Detailed clinical history was taken
      from each patient. PCOS was diagnosed on the basis of ultrasonography. Hormonal
      assays included fasting blood sugar, postprandial blood sugar, follicle
      stimulating hormone, luteinizing hormone, thyroid stimulating hormone,
      dehydroepiandrostenedione, prolactin, free testosterone, fasting lipid profile
      and sex hormone binding globulin. The results obtained were statistically
      correlated. RESULTS: In our study, the prevalence of cutaneous manifestations was
      90%. Of all the cutaneous manifestations acne was seen in highest percentage
      (67.5%), followed by hirsutism (62.5%), seborrhea (52.5%), androgenetic alopecia
      (AGA) (30%), acanthosis nigricans (22.5%) and acrochordons (10%). Fasting insulin
      levels was the most common hormonal abnormality seen in both acne and hirsutism,
      whereas AGA was associated with high testosterone levels. CONCLUSION: The
      prevalence of cutaneous manifestations in PCOS was 90%. Hirsutism, acne,
      seborrhea, acanthosis nigricans and acrochordons were associated with increased
      levels of fasting insulin, whereas AGA showed higher levels of serum
      testosterone.

PMID- 26288424
TI  - A Study of Clinical Profile of Vitamin B12 Deficiency with Special Reference to
      Dermatologic Manifestations in a Tertiary Care Hospital in Sub-Himalayan Bengal.
AB  - BACKGROUND: Vitamin B12 deficiency is thought to be uncommon in the eastern parts
      of India including Bengal and the eastern states as compared to the northern and
      southern parts of India. The importance of cutaneous features in relation to
      vitamin B12 deficiency is not well described in literature. AIM: To know the
      clinical profile of vitamin B12 deficiency in this region and to find out if
      there is any relationship between dermatologic manifestations with vitamin B12
      deficiency. MATERIALS AND METHODS: All symptomatic patients of anemia requiring
      blood transfusions who had either raised mean corpuscular volume (MCV) or
      bicytopenia/pancytopenia on complete blood count or were symptomatic in the form
      of skin hyperpigmentation were screened for vitamin B12 deficiency. RESULTS:
      Twenty-five patients were tested for vitamin B12 deficiency. Of them 19 patients
      were found to be having vitamin B12 deficiency. CONCLUSIONS: Vitamin B12
      deficiency is not uncommon in the eastern parts of India, contrasting the
      previous thoughts that it was uncommon in this area, though larger studies are
      required to know it better. This study included only those requiring blood
      transfusions, thus a much higher prevalence is expected in this area. Patients
      with vitamin B12 deficiency do present with severe anemia requiring blood
      transfusions and often have skin hyperpigmentation.

PMID- 26288425
TI  - Study of the International Epidemiology of Androgenetic Alopecia in Young
      Caucasian Men Using Photographs From the Internet.
AB  - BACKGROUND: The epidemiological evaluation of androgenetic alopecia (AGA) is
      based mainly on direct observation and questionnaires. The international
      epidemiology and environmental risk factors of AGA in young Caucasian men remain
      unknown. AIM: To use photographs and data from the Internet to evaluate severe
      AGA and generate greater understanding of the international epidemiology of the
      disorder in young Caucasian men. MATERIALS AND METHODS: A population-based cross
      sectional study design was used. The sample included 26,340 Caucasian men aged 30
      to 40 years who had uploaded profiles to two dating websites. Their photographs
      were evaluated for AGA and graded as follows: severe AGA (Norwood type VI-VII),
      non-severe AGA, and unknown. Epidemiological data were collected from the sites.
      Logistic regression was used to analyze the effect of risk factors on the
      prevalence of severe AGA. RESULTS: The overall success rate for identifying
      severe AGA by indirect evaluation of Internet photographs was 94%. The prevalence
      of severe AGA was 15.33% overall and varied significantly by geographical region.
      The risk of having severe AGA was increased by 1.092 for every year of age
      between 30 and 40 years. Severe AGA was more prevalent in subjects with higher
      body mass index. CONCLUSIONS: Photographs from the Internet can be used to
      evaluate severe AGA in epidemiological studies. The prevalence of severe AGA in
      young Caucasian men increases with age and varies by geographical region. Body
      mass index is an environmental risk factor for severe AGA.

PMID- 26288426
TI  - Therapeutic Plasma Exchange-A New Dawn in the Treatment of Pemphigus Vulgaris.
AB  - Pemphigus vulgaris is an autoimmune disorder that involves intraepithelial
      blistering and sores of skin and mucous membrane. It generally correlates with
      the levels of circulating autoantibodies; their removal seems a reasonable
      therapeutic approach. Therapeutic plasma exchange is hypothesized to remove
      pathogenic autoantibodies and has been used in refractory or severe cases. It may
      be considered for rapid control of severe or recalcitrant pemphigus vulgaris and
      should be combined with use of concomitant immuno-suppressive. 

PMID- 26288427
TI  - Vorinostat-An Overview.
AB  - Vorinostat is a new drug used in the management of cutaneous T cell lymphoma when
      the disease persists, gets worse or comes back during or after treatment with
      other medicines. It is an efficacious and well tolerated drug and has been
      considered a novel drug in the treatment of this condition. Currently apart from
      cutaneous T cell lymphoma the role of Vorinostat for other types of cancers is
      being investigated both as mono-therapy and combination therapy. 

PMID- 26288428
TI  - Onychomadesis with Lichen Planus: An Under-Recognized Manifestation.
AB  - Onychomadesis or proximal separation of the nail pate usually results from
      severe, generalized dermatoses like bullous diseases, hand foot and mouth
      disease, varicella or severe cutaneous drug reactions. Although lichen planus
      (LP) produces varied nail manifestations (longitudinal onychorrhexis,
      onychoschizia, nail pigmentation, pterygium etc.), to the best of our knowledge,
      onychomadesis as a manifestation of nail LP is not recorded. This report presents
      two children with onychomadesis arising with generalized eruptive LP. 

PMID- 26288429
TI  - Subcutaneous Infraorbital Dirofilariasis.
AB  - Dirofilariasis is a parasitic infection transmitted by mosquitoes from domestic
      and wild animals. Humans accidentally get infected and can present with a lung
      nodule, subcutaneous mass or an ocular lesion which will be either
      subconjunctival or periorbital. Proper microbiological and histopathological
      examinations aid in proper diagnosis. Herein, we present a case report of a 64
      year-old female patient from Kerala with an infraorbital mass diagnosed as
      dirofilariasis. 

PMID- 26288430
TI  - A Florid Case of Iatrogenic Cushing's Syndrome Induced by Topical Steroid with
      Osteoporosis and Hypogonadism.
AB  - Here we report a case of a young male who developed full blown iatrogenic
      Cushing's syndrome after use of superpotent clobetasol propionate cream 0.05% for
      long duration to suppress psoriatic skin lesions. He also developed osteoporosis
      and hypogonadism. This case demonstrates that injudicious use of topical steroids
      can have disastrous consequences. 

PMID- 26288431
TI  - Solitary Ulcerated Congenital Giant Juvenile Xanthogranuloma.
AB  - A 3-month-old female patient with a giant ulcerated nodule over the back since
      birth was diagnosed as congenital giant juvenile xanthogranuloma (JXG) based on
      clinical and histopathological examination. Congenital giant JXG with ulceration
      at birth is a rare presentation of JXG and commonly misdiagnosed. This case
      emphasizes the importance of being aware of the myriad presentations of JXG in
      order to make a correct diagnosis and avoid unnecessary investigations or
      treatment. 

PMID- 26288432
TI  - Extragenital Lichen Sclerosus et Atrophicus.
AB  - Lichen sclerosus et atrophicus (LSA) is a chronic inflammatory dermatosis with
      anogenital and extragenital presentations. Extragenital lichen sclerosus is most
      common on the neck, shoulders and upper trunk. Linear lesions are uncommon in
      LSA. We report a case of linear extragenital LSA involving forehead and scalp,
      along with grouped white papules of LSA in the right side of the back in a
      postmenopausal woman. The patient showed atypical clinical presentation of LSA in
      face which clinically mimicked 'en coup de sabre' as seen in morphea, but other
      clinical features suggested the diagnosis of LSA and the histopathological
      findings confirmed it. 

PMID- 26288433
TI  - Unilateral Ulcerating Clear-Cell Syringomas Involving Left Groin in a Non
      Diabetic Woman - Report of a Rare Presentation.
AB  - Clear-cell syringomas, a rare histologic variant of syringomas, frequently
      coexist with diabetes mellitus. Clinically, it presents as skin colored papules
      distributed symmetrically around periorbital region. However, asymmetrical
      distribution of syringomas is rare and much rarer is the ulceration in such
      syringomas. Ulceration in such asymmetrical syringomas has not been reported so
      far. Herein, we report ulceration of clear-cell syringomas involving left groin
      in a middle aged non-diabetic woman. 

PMID- 26288434
TI  - Homozygous Familial Hypercholesterolemia Associated with Symmetric Subcutaneous
      Lipomatosis.
AB  - Homozygous familial hypercholesterolemia is an autosomal dominant disorder of
      lipid metabolism, characterized by reduced clearance of low-density lipoprotein
      cholesterol and a high risk of rapid development of cardiovascular diseases. Its
      incidence is relatively rare and estimated to be one in one million in general
      populations. Here, we report homozygous familial hypercholesterolemia in two
      Egyptian young siblings, presented with cutaneous, tendinous xanthomas, and
      corneal arcus. One of them has symmetric subcutaneous lipomatosis, which has not
      been reported before in association with familial hypercholesterolemia. 

PMID- 26288435
TI  - Tuberous Sclerosis Complex: Diagnostic Role of Magnetic Resonance Imaging.
AB  - Tuberous sclerosis complex (TSC) is a well-known clinical entity, characterized
      by facial angio-fibroma, shagreen patch, and hypo-melanotic, and confetti-like
      skin lesions. An exquisite fresh case is being narrated, emphasizing its
      microscopic pathology. The role of magnetic resonance imaging of the brain, in
      particular, is highlighted to define the large variety of neurological abrasions
      for determining its future progression. 

PMID- 26288436
TI  - Multidimensional Ultrasound and Computed Tomography Imaging Support in Bleeding
      Plexiform Neurofibromatosis of the Scalp: A Case Report and Literature Review.
AB  - Active bleeding in plexiform neurofibromatosis can be a life-threatening
      complication in neurofibromatosis type 1 (NF1). The prompt imaging support of 2D
      3D ultrasound (US) and computed tomography (CT) during the active hemorrhage
      phase of cutaneous neurofibromas has not been previously reported. We report a
      case with NF1 who experienced a sudden swelling in the parieto-temporal region
      that corresponded to a massive and active hemorrhage within a plexiform
      neurofibroma. The US and CT imaging characteristics of this bleeding tumor are
      shown. Active hemorrhage in a plexiform neurofibroma of the scalp appeared in US
      as a heterogeneous hypodermal mass. CT demonstrated a fully hyperdense soft
      tissue mass. These characteristics differ from the non-complicated or old
      hemorrhagic imaging appearances of scalp plexiform neurofibromas and encourage
      prompt surgical treatment. This case report demonstrates the usefulness of
      imaging support in the early diagnosis of this hemorrhagic complication of NF1 in
      the scalp and also stimulates multispecialty management. 

PMID- 26288437
TI  - Nevus Comedonicus Syndrome.
AB  - A case of nevus comedonicus syndrome with atypical cutaneous presentation
      (widespread involvement without any particular pattern, midline lesions involving
      lower abdomen and involvement of bilateral pinna), and some unusual skeletal
      (adduction deformity involving bilateral metatarsal along with medial deviation
      at the level of tarsometatarsal joint), central nervous system (agenesis of
      corpus callosum with a interhemispheric cyst), visceral (pancreatic cyst) and
      neurological manifestations have been illustrated. 

PMID- 26288438
TI  - Tranexamic Acid-Induced Fixed Drug Eruption.
AB  - A 33-year-old male showed multiple pigmented patches on his trunk and extremities
      after he took tranexamic acid for common cold. He stated that similar eruptions
      appeared when he was treated with tranexamic acid for influenza 10 months before.
      Patch test showed positive results at 48 h and 72 h by 1% and 10% tranexamic acid
      at the lesional skin only. To our knowledge, nine cases of fixed drug eruption
      induced by tranexamic acid have been reported in Japan. Tranexamic acid is a safe
      drug and frequently used because of its anti-fibrinolytic and anti-inflammatory
      effects, but caution of inducing fixed drug eruption should be necessary. 

PMID- 26288439
TI  - Ectodermal Dysplasia-Skin Fragility Syndrome: A Rare Case Report.
AB  - Ectodermal dysplasia/skin fragility syndrome (ED-SFS) is a newly described
      autosomal recessive disorder characterized by skin fragility and blistering,
      palmoplantar keratoderma, abnormal hair growth, nail dystrophy, and occasionally
      defective sweating. It results from mutations in the PKP1 gene encoding
      plakophilin 1 (PKP1), which is an important component of stratifying epithelial
      desmosomes and a nuclear component of many cell types. Only 12 cases of this rare
      genodermatosis have been reported so far. We present an unusual case of ED-SFS in
      a 12-year boy who was normal at birth but subsequently developed skin fragility,
      hair and nail deformities, abnormal dentition, palmoplantar keratoderma, and
      abnormal sweating but no systemic abnormality. 

PMID- 26288440
TI  - Hidradenocarcinoma: A Rare Sweat Gland Neoplasm Presenting as Small Turban Tumor
      of the Scalp.
AB  - Hidradenocarcinomas are very rare malignant sweat gland tumors that possess an
      infiltrative and/or low metastatic potential. Here we describe an interesting
      case of hidradenoma on the fronto-parietal region of the scalp of an elderly
      female, part of which had developed carcinomatous changes, infiltrating up to the
      pericranium. She developed intense itching, pain, spontaneous ulceration and
      rapid increase in the size of the tumor correlating with the expression of
      malignant behavior of the neoplasm. An initial incision biopsy suggested features
      of benign poroid hidradenoma, while the histology from the excised tumor
      exhibited a fairly well circumscribed epithelial neoplasm in dermis consisting of
      interconnected nodules as well as differentiated ducts, the neoplastic cells
      showing mild pleomorphism of nuclei, mitotic figures and abundant pale cytoplasm.
      Clefts, sclerotic stroma and foci of necrosis en mass were also seen. The final
      diagnosis was a well differentiated and slow growing hidradenocarcinoma. The
      tumor recurred locally despite total excision. 

PMID- 26288441
TI  - Multifocal Annular Tufted Angioma: An Uncommon Clinical Entity.
AB  - Tufted angioma (TA) is a localized benign hamartomatous vascular proliferation
      usually presenting in the childhood as an erythematous plaque. We report here a
      rare case of multifocal TA in an 8-year-old boy who presented which two large
      annular lesions as well as multiple papules and nodules on the back for the
      duration of 4 years. Histology showed typical well circumscribed poorly canalized
      vascular lobules with 'cannon ball' configuration. 

PMID- 26288442
TI  - Acute Generalized Exanthematous Pustulosis Due to Insect Bites?
AB  - Acute generalized exanthematous pustulosis is a rare severe cutaneous adverse
      reaction pattern that is mostly caused by the intake of drugs and rarely
      associated with viral infections, food allergens or toxins. Here we present the
      report of three patients who got admitted in our hospital for generalized
      pustulosis and fever after insect bites. The diagnosis of acute generalized
      exanthematous pustulosis was made by EuroSCAR scoring. The drug etiology was
      excluded and spider bite was implicated as the etiological agent in these cases
      of AGEP which are the first such reported cases in India. 

PMID- 26288443
TI  - Creeping Eruption on the Move: A Case Series from Northern India.
AB  - Cutaneous larva migrans (CLM) is the most common tropically acquired dermatosis
      caused by infection with hookworm larvae. It is commonly seen in tropical areas,
      and in people who have a history of foreign travel and of walking barefoot on
      sandy soil or beaches. An increased incidence has been seen in non-endemic areas
      due to change in environmental and behavioral factors. The presence of this
      entity is questionable in Northern region as the environmental conditions and the
      type of soil is not favorable, both of which are required for the survival of
      nematode. We describe a case series of six patients presented during winter
      season in the outpatient department of Dermatology within a short period of 2
      months. We also review the clinical features of various other creeping eruptions
      and factors that are responsible for boosting infection in North India. 

PMID- 26288444
TI  - Pseudomembranous-like Tinea of the Scrotum Infected by Microsporum Gypseum in a
      Young Man.
AB  - Microsporum gypseum is a geographically widespread geophilic fungus that infects
      animals and humans. M. gypseum infection on the scrotum is very rare and can be
      easily misdiagnosed because of a lack of inflammatory reaction. Here we describe
      a patient with pseudomembranous-like tinea of the scrotum resulting from M.
      gypseum. 

PMID- 26288445
TI  - A dramatic presentation of an unusual form of cutaneous lymphoma.
AB  - We report an unusual and dramatic presentation of a rare form of cutaneous
      lymphoma, known as subcutaneous panniculitis-like T-cell lymphoma (SPTCL). This
      patient presented with a pruritic, florid and purpuric rash that was diagnosed as
      lobular panniculitis and treated with oral steroids for 1 year with no success.
      His skin lesions would return each time oral corticosteroids were being weaned
      off. Upon presentation to our clinic, repeated deep skin biopsies with
      immunohistochemical analysis coupled with the clinical history of persistent B
      symptoms and the presence of pancytopenia helped clinched the rare diagnosis of
      SPTCL with hemophagocytosis. The patient was then started on cyclosporine and
      dexamethasone before definitive chemotherapy. This rare and diagnostically
      challenging condition is commonly misdiagnosed as benign panniculitis or eczema,
      and highlights the importance of repeated skin biopsies. 

PMID- 26288446
TI  - Acquired Idiopathic Generalized Anhidrosis.
AB  - Acquired idiopathic generalized anhidrosis is a rare condition, where the exact
      pathomechanism is unknown. We report a case of acquired idiopathic generalized
      anhidrosis in a patient who later developed lichen planus. Here an autoimmune
      mediated destruction of sweat glands may be the probable pathomechanism. 

PMID- 26288447
TI  - Pemphigoid Vegetans in Childhood: A Case Report and Short Review of Literature.
AB  - Pemphigoid vegetans is a very rare type of bullous pemphigoid which usually
      affects the elderly and has not been reported in children. It shows a clinical
      resemblance to pemphigus vegetans but has distinct histological and
      immunopathological features of bullous pemphigoid. A 9-year-old girl presented
      with recurrent purulent and verrucous vegetating lesions on her forehead, groin
      and vulva along with scaling, crusted, bullous and purulent lesions on the
      eyelids, periorbital, periauricular, perioral region and lips. She had oral
      lesions and a cerebriform tongue. Though she showed clinical features of
      pemphigus vegetans, histology revealed a subepidermal blister with the absence of
      acantholysis. Direct immunofluorescence studies were suggestive of bullous
      pemphigoid. On clinicopathological correlation, a diagnosis of pemphigoid
      vegetans was made. She responded well to oral corticosteroids and dapsone therapy
      with complete resolution of the lesions. 

PMID- 26288448
TI  - Darier's Disease in Gastric Malignancy: An Unusual Paraneoplastic Phenomenon.
AB  - Darier's disease is an autosomal dominant genodermatosis resulting from ATP2A2
      gene mutation. A 62-year-old male presented at our outpatient (OPD) with sudden
      onset numerous dirty, warty papules over the head, neck, and back since 2 months.
      Histopathology of the skin lesions revealed acantholytic dyskeratosis suggestive
      of Darier's disease. He was referred to the gastroenterology department for some
      gastrointestinal (GI) symptoms where he was diagnosed with adenocarcinoma of the
      stomach and was subsequently operated. On his next visit to our department for
      follow-up, we found a marked diminution of the skin lesions in the absence of any
      specific treatment. In view of the above finding, we concluded that
      paraneoplastic dermatosis in the form of Darier's disease occurred in this
      patient. Paraneoplastic Darier's disease with gastric adenocarcinoma is not yet
      described in dermatology literature and is hence reported here. 

PMID- 26288449
TI  - Vascular Tumor on the Forehead of an HIV Patient.
AB  - Cirsoid aneurysm is a small vascular proliferation characterized by small to
      medium-sized channels with features of arteries and veins, that present as small,
      blue or red asymptomatic papule. We report a case of a crisoid aneurysm on the
      forhead of an HIV patient that suggested a Kaposi sarcoma as a differential
      diagnosis. 

PMID- 26288450
TI  - Acral Acanthosis Nigricans in a Case of Scleroderma.
AB  - Acanthosis nigricans (AN) is a dermatosis characterized by velvety,
      papillomatous, brownish-black, hyperkeratotic plaques, typically on the
      intertriginous surfaces and neck. The majority (80%) of AN occurs idiopathically
      or in benign conditions such as endocrinopathies like diabetes mellitus,
      polycystic ovary syndrome; metabolic syndrome and/or heritable disease.
      Malignancy-associated AN is rare. AN may rarely be associated with autoimmune
      diseases including systemic lupus erythematosus, due to antibodies to the insulin
      receptor, so-called type B insulin resistance. Here we report a case of AN in a
      case of diffuse progressive systemic sclerosis without evidence of insulin
      resistance. 

PMID- 26288451
TI  - Extramammary Paget's Disease in Two Brothers.
AB  - Extramammary Paget's disease (EMPD), which is considered to be an adenocarcinoma
      of the apocrine glands, is a rare, slow-growing neoplasm. The standard treatment
      for local EMPD is surgical resection, however, so far, no effective treatment is
      found for advanced EMPD. Trastuzumab, which is a recombinant monoclonal antibody
      against the human epidermal growth factor receptor 2 HER2 has been proved to be
      effective in the treatment of advanced EMPD in some cases where HER2 protein is
      overexpressed. Herein, we report two cases of EMPD in two brothers. The younger
      brother who presented as local EMPD on the scrotum received surgical resection
      and had no recurrence in 15 months following. The older brother suffered from
      invasive EMPD also on the scrotum with inguinal region multiple metastatic lymph
      nodes and was treated with combination chemotherapy and Trastuzumab to target
      HER2 consecutively after a wide surgical excision. 

PMID- 26288452
TI  - Kyrle's Disease Presenting in an Extensive Distribution along Lines of Blaschko.
AB  - A 24-year-old lady presented with the complaints of asymptomatic dark, raised
      lesions over her body since past 4 years. Dermatological examination revealed
      hyperkeratotic, hyperpigmented papules in a Blaschkoid distribution over trunk
      and extremities. The hyperkeratotic lesions could be removed leaving behind a
      small crater. Skin biopsy revealed hyperkeratosis, parakeratosis with epidermal
      invagination, focal cornified plug with basophilic degenerated material and
      dyskeratotic keratinocytes. Dermis showed dilated capillaries with moderate
      amount of perivascular lymphocytic infiltrate and granulomatous lymphocytic
      infiltrate in the deep dermis. A diagnosis of Kyrle's disease was made and
      patient was started on oral acitretin 25 mg daily with satisfactory response to
      therapy. This is the first reported instance of Kyrle's disease occurring in an
      extensive Blaschkoid distribution. 

PMID- 26288453
TI  - Bowen's Disease of the Nipple and Areola in an Old Man.

PMID- 26288454
TI  - An Unusual Case of Neonatal Langerhans Cell Histiocytosis Presenting with Diffuse
      Hemorrhagic Nodules and a Cutaneous Abdominal Mass.

PMID- 26288455
TI  - Isotretinoin-Induced Night Blindness.

PMID- 26288456
TI  - Diclofenac-induced Sweet's syndrome.

PMID- 26288457
TI  - Multiple Myeloma with Cutaneous Deposits as Rare Lymphoplasmacytoid Cells.

PMID- 26288458
TI  - Toxic Epidermal Necrolysis Following Phenytoin and Cranial Irradiation.

PMID- 26288459
TI  - Non-folliculotropic Milia in a Treated Case of Mycosis Fungoides: A Rare
      Occurrence.

PMID- 26288460
TI  - Human Papillomavirus Deoxyribonucleic Acid in Non-Genital Benign Papillomatous
      Skin Lesion.

PMID- 26288461
TI  - Firm Skin-Colored Nodules on the Scalp.

PMID- 26288462
TI  - A Painless Nodule on the Face of 60 Year Old Female.

PMID- 26288463
TI  - Antimicrobial resistance and inappropriate use of antimicrobials: Can we rise to
      the challenge?

PMID- 26288464
TI  - Paperless clinical trials: Myth or reality?
AB  - There is an urgent need to expedite the time-to-market for new drugs and to make
      the approval process simpler. But clinical trials are a complex process and the
      increased complexity leads to decreased efficiency. Hence, pharmaceutical
      organizations want to move toward a more technology-driven clinical trial process
      for recording, analyzing, reporting, archiving, etc., In recent times, the
      progress has certainly been made in developing paperless systems that improve
      data capture and management. The adaptation of paperless processes may require
      major changes to existing procedures. But this is in the best interests of these
      organizations to remain competitive because a paperless clinical trial would lead
      to a consistent and streamlined framework. Moreover, all major regulatory
      authorities also advocate adoption of paperless trial. But challenges still
      remain toward implementation of paperless clinical trial process. 

PMID- 26288465
TI  - Imiquimod - Its role in the treatment of cutaneous malignancies.
AB  - Imiquimod is a synthetic imidazoquinolone amine, which has potent immune response
      modifier activity, when topically used. This characteristic property of imiquimod
      has led to its use in a number of applications in dermatology, particularly in
      cutaneous malignancies, where it has been found to be effective and safe.
      Currently, additional mechanisms for its activity in actinic keratosis, basal
      cell carcinoma, and invasive squamous cell carcinoma have been elucidated. Its
      usage for cutaneous metastasis in breast cancer has been a further addition to
      its therapeutic armamentarium recently. 

PMID- 26288466
TI  - Estimation of the plasma effect site equilibration rate constant of sufentanil in
      children using the time to peak effect of heart rate and blood pressure.
AB  - OBJECTIVES: Although targeting the effect site concentration may offer advantages
      over the traditional forms of administering intravenous anesthetics, it is not
      applicable for sufentanil in children because its plasma effect site
      equilibration rate constant (ke0) is not known yet. We estimated ke0 of
      sufentanil in children using the time to peak effect (t peak) method. MATERIALS
      AND METHODS: Under general anesthesia, sufentanil t peak was measured after
      administration of a submaximal bolus dose by means of the decrease in heart rate,
      blood pressure and calculated approximate entropy (ApEn) of electroencephalogram
      in 105 children (age range: 3-11 years). ke0 was estimated using t peak and known
      sufentanil pharmacokinetic parameters in normal children. RESULTS: The mean t
      peaks were measured as 44 +/- 22 s and 227 +/- 91 s by heart rate and by mean
      blood pressure respectively. The estimated ke0 were 5.16/min and 0.49/min by
      heart rate and blood pressure respectively. t peak could not be measured using
      the ApEn, thus ke0 could not be calculated by ApEn in children. CONCLUSIONS:
      Shorter measured sufentanil t peak by heart rate compared to blood pressure
      indicate that the heart rate decrease faster than decreasing of blood pressure.
      Moreover, the calculated sufentanil ke0 in children depends on the
      pharmacodynamics parameters.

PMID- 26288467
TI  - Comparative evaluation of 2 g single dose versus conventional dose azithromycin
      in uncomplicated skin and skin structure infections.
AB  - OBJECTIVES: Uncomplicated skin and skin structure infections (uSSSIs) are a
      common clinical problem. Majority are caused by staphylococci and streptococci.
      Different oral antibiotics are used for uSSSI, with comparable efficacy but
      varying treatment duration, cost, and adverse event profile. Azithromycin is used
      in uSSSI in adults conventionally in a dose of 500 mg once for 5 days. The
      extensive tissue distribution of the drug and its long elimination half-life
      prompted us to explore whether a single 2 g dose of the drug would produce a
      response in uSSSI comparable to conventional dosing. MATERIALS AND METHODS: We
      conducted a parallel group, open-label, randomized, controlled trial
      (CTRI/2015/07/005969) with subjects of either sex, >=12 years of age, presenting
      with uSSSI to the dermatology outpatient department. One group (n = 146) received
      2 g single supervised dose while the other (n = 146) received conventional dose
      of 500 mg once daily for 5 days. Subjects were followed up on day 4 and day 8.
      Complete clinical cure implied complete healing of lesions, without residual
      signs or symptoms, within 7 days. RESULTS: High cure rate was observed in both
      arms (97.97% and 98.63%, respectively) along with noticeable improvement in
      symptom profile from baseline but without statistically significant difference
      between groups. However, excellent adherence (defined as no tablets missed) was
      better in single dosing arm (98.65% vs. 86.30%). Tolerability was also comparable
      between groups with the majority of adverse events encountered being
      gastrointestinal in nature and mild. CONCLUSIONS: Single 2 g azithromycin dose
      achieved the same result as conventional azithromycin dosing in uSSSI with
      comparable tolerability but with the advantage of assured adherence. This dose
      can, therefore, be recommended as an alternative and administration supervised if
      feasible.

PMID- 26288468
TI  - Antimicrobial drug prescribing patterns for community-acquired pneumonia in
      hospitalized patients: A retrospective pilot study from New Delhi, India.
AB  - OBJECTIVE: The objective of this study was to determine patterns and frequency of
      antimicrobial drug use among hospitalized patients with community-acquired
      pneumonia (CAP). METHODOLOGY: A retrospective 5 years (April 2007-March 2012)
      detailed medical record review of patients diagnosed with CAP and discharged to
      home from Non-Intensive Care Unit respiratory medicine wards of two public
      hospitals in Delhi. RESULTS: A total of 261 medical records were analyzed. Over
      the 5 years, 82.0% (2007-08), 78.6% (2008-09), 59.5% (2009-10), 64.7% (2010-11),
      and 67.8% (2011-12) patients were prescribed two antimicrobials. In the last two
      study years, the proportion of patients receiving three antimicrobials increased
      (from 2.0% to 26.5% and 28.8%), while the proportion receiving monotherapy
      decreased (from 16.0% to 8.8% and 3.4%). In accordance with guidelines, beta
      lactams and macrolides were the two most frequently prescribed antimicrobials
      (34.1%). However, newer generation beta-lactams were prescribed. A total of 37
      patients were prescribed beta-lactam-tazobactam combination preparations.
      Overall, beta-lactams constituted more than 40% of prescriptions while macrolides
      were the second most prescribed class. Cephalosporin prescriptions significantly
      increased (P < 0.01) and penicillin prescriptions significantly decreased over
      study periods. The prescription of fluoroquinolones also decreased (21.5-6.0%, P
      < 0.01) and aminoglycoside prescription ranged from 9.7% to 16.4%, over 5 years.
      Reasons for prescribing three antimicrobials, use of aminoglycosides, or higher
      end/reserve antibiotics were not mentioned in the medical records. There were no
      hospital-specific guidelines for doctors to follow in the treatment of CAP.
      CONCLUSIONS: These findings suggest the need for implementing antimicrobial
      treatment guidelines. Adequate documentation and monitoring of antibiotic use for
      feedback are also lacking. An antimicrobial stewardship program may offer the
      most comprehensive solution for appropriate use of antimicrobials.

PMID- 26288469
TI  - Evaluation of acute effects of melatonin on ethanol drinking in ethanol naive
      rats.
AB  - OBJECTIVE: The objective was to evaluate the acute effect of melatonin on ethanol
      drinking in ethanol naive rats and to determine the specificity of the effect of
      melatonin on ethanol intake as compared to an intake of plain tap water or sugar
      water. MATERIALS AND METHODS: A total of three experiments (2 weeks duration
      each) using different drinking solutions (ethanol, plain tap water, sugar water)
      was conducted in individually housed male wistar rats of 5 weeks age. Each animal
      had access to bottles containing drinking solutions for 2 h a day. In each
      experiment, on day 1, day 2, day 4, day 5, day 8, day 9, day 11, day 12 rats
      received drinking solutions. Each individual rat received single doses of saline,
      melatonin (50 mg and 100 mg/kg), and naltrexone on day 2, 5, 9, and 12, 1-h
      before receiving drinking solution. The order of drug administration is permuted
      such a way that each animal received the drugs in a different order in different
      experiments. RESULTS: Melatonin has significantly decreased ethanol consumption
      by the rats and effect is dose-dependent. Naltrexone also has caused a
      significant reduction in the ethanol consumption. The maximum reduction in
      ethanol consumption was seen with melatonin 100 mg/kg dose compared to melatonin
      50 mg/kg and naltrexone. There was no statistically significant effect of
      melatonin on plain water and sugar solution intake. CONCLUSIONS: Melatonin
      decreases ethanol consumption in ethanol naive rats. The effect of melatonin is
      similar to naltrexone affecting selectively ethanol consumption, but not plain
      water and sugar water consumption.

PMID- 26288470
TI  - Modulation of muscarinic system with serotonin-norepinephrine reuptake inhibitor
      antidepressant attenuates depression in mice.
AB  - OBJECTIVE: Several studies suggest that muscarinic receptor antagonist
      scopolamine is a rapidly acting antidepressant for the treatment-resistant
      depression. Therefore, this study was carried out to investigate the possibility
      of synergistic potential of scopolamine with antidepressants for the treatment of
      depression without memory impairment in mice. MATERIALS AND METHODS:
      Antidepressants such as citalopram, duloxetine, fluvoxamine, and venlafaxine at
      their median effective dose that is 12.5, 42.8, 17.5, 15.7 mg/kg p.o.,
      respectively, were evaluated in combination with scopolamine 0.2 mg/kg
      intraperitoneally for the synergistic potential for ameliorating depression in
      Swiss albino mice. A battery of tests including forced swim test (FST) and tail
      suspension test (TST) were performed in all the groups comprising vehicle
      control, scopolamine, antidepressants per se, and the combinations of
      antidepressants with scopolamine. This was followed by the locomotor activity and
      memory tests. RESULTS: Behavioral studies indicated that only antidepressant
      venlafaxine with scopolamine resulted in 95.5% and 93.6% reduction in immobility
      time compared to the vehicle control in FST and TST, respectively. This is
      significant (P < 0.0001) synergistic hyper-additive antidepressive-like effect
      compared to scopolamine per se and venlafaxine per se treatment effects in
      antidepressant paradigms. All the data were evaluated using the one-way analysis
      of variance followed by individual comparisons using Tukey's post-hoc test.
      Control open field studies demonstrated no significant increase in general
      locomotion after co-administration of the compounds. Step down avoidance paradigm
      confirmed that scopolamine at the selected dose has no cognition deficit in any
      mice. CONCLUSIONS: The dose of scopolamine selected for synergistic potential has
      no detrimental effect on memory. The present results suggest the concoction of
      scopolamine with venlafaxine for enhanced synergistic antidepressive effects with
      the reduction of dose.

PMID- 26288471
TI  - Immunoprophylactic potential of wheat grass extract on benzene-induced leukemia:
      An in vivo study on murine model.
AB  - OBJECTIVES: Wheat grass (Triticum aestivum) is a gift of nature given to mankind.
      A number of scientific research on wheatgrass establishes its anticancer and
      antioxidant potential. Current work was focused to determine antileukemic effect
      of wheat grass. MATERIALS AND METHODS: The commercial wheatgrass powder was
      extracted with 95% of methanol. Methanol extract of wheat grass was studied for
      acute oral toxicity as per revised Organization for Economic Cooperation and
      Development Guidelines number 423. Leukemia was successfully induced in Wister
      rats by intravenous injection of benzene. The blood was collected and analyzed
      for hematological parameters. Phagocytotic activity of the extract was
      determined. RESULTS: Phytochemical screening revealed the presence of flavonoids,
      phenolics, carbohydrates, and amino acids. From acute toxicity studies, it was
      found that the methanol extract of wheatgrass was safe up to a dose level of 2000
      mg/kg of body weight. Outcomes of hematological parameters in various
      experimental groups of murine model demonstrated antileukemic effect of extract.
      Methanol extract of wheatgrass aroused the process of phagocytosis of killed
      Candida albicans and also demonstrated a significant chemotactic activity at all
      tested concentrations. CONCLUSION: In the current work, methanol extract of wheat
      grass demonstrated antileukemic potential that might be due to the presence of
      flavonoids and polyphenolics in it. Further isolation, structural
      characterization of active constituents is necessary to extrapolate the mechanism
      of action.

PMID- 26288472
TI  - Anti-hyperbilirubinemic and wound healing activity of aqueous extract of
      Calotropis procera leaves in Wistar rats.
AB  - AIMS: The aim of this study was to evaluate the bilirubin lowering and wound
      healing property of aqueous extract of Calotropis procera (AECP) leaves in Wistar
      rats. MATERIALS AND METHODS: Albino Wistar rats of either sex were used for the
      study. Bilirubin lowering property of C. procera leaves was evaluated using
      phenylhydrazine and paracetamol as inducing agents followed by measuring the
      concentration of serum total bilirubin in hyperbilirubinemic rats. Wound healing
      property was evaluated using incision and excision models by measuring tensile
      breaking strength, percentage wound contractions, and epithelization days,
      respectively. STATISTICAL ANALYSIS: Statistical comparison between groups in each
      experiment was done with one-way analysis of variance followed by Dunnett's test.
      RESULTS: AECP showed a significant (P < 0.05) decrease in concentrations of serum
      total bilirubin in hyperbilirubinemic rats as well as significant (P < 0.05)
      increase in breaking strength and percentage wound contractions with decreased
      epithelization period when compared to control groups. CONCLUSIONS: AECP showed
      significant bilirubin lowering and wound healing property in Wistar rats.

PMID- 26288473
TI  - Neuroprotective potential of Beta vulgaris L. in Parkinson's disease.
AB  - OBJECTIVE: The objective was to investigate the neuroprotective role of Beta
      vulgaris in Parkinson's disease (PD). MATERIALS AND METHODS: PD was induced by
      administration of reserpine (5 mg/kg/day, i.p for 5 consecutive days),
      haloperidol (1 mg/kg, i.p.), and tacrine (2.5 mg/kg, i.p.) in experimental
      animals. The symptoms of PD such as tremors, akinesia, rigidity, catalepsy, and
      vacuous chewing movements (VCMs) were evaluated. Foot shock-induced aggression
      (FSIA) model was used to confirm anti-parkinsonian activity. The methanolic
      extract of Beta vulgaris (MEBV) was administered at doses of 100, 200, and 300
      mg/kg, p.o. The combination of L-dopa and carbidopa was used as a standard drug.
      Behavioral studies such as locomotor activity and grip strength were determined,
      and oxidative stress was evaluated in FSIA model in rat brain. RESULTS:
      Pretreatment with MEBV (200 and 300 mg/kg) significantly reduced the intensity of
      muscular rigidity, duration of catalepsy, akinesia, the number of tremors, VCMs,
      and increase fighting behavior. The locomotor activity and grip strength were
      significantly increased by MEBV. In FSIA, the biochemical analysis of brain
      revealed the increased level of lipid peroxidation (LPO) and decreased levels of
      superoxide dismutase (SOD) and catalase (CAT). MEBV significantly reduced LPO
      level and restored the defensive antioxidant enzymes SOD and CAT in rat brain.
      CONCLUSIONS: The results indicated the protective role of B. vulgaris against PD.
      The mechanism of protection may be due to augmentation of cellular antioxidants.

PMID- 26288474
TI  - Evaluation of skeletal muscle relaxant activity of aqueous extract of Nerium
      oleander flowers in Albino rats.
AB  - OBJECTIVES: Nerium oleander is traditionally used in various diseases because of
      its medicinal properties. One of its uses is in musculoskeletal disorder. The aim
      of the study was to evaluate the skeletal muscle relaxant activity of the aqueous
      extract of Nerium oleander flowers (AENOF) in albino rats in comparison with
      diazepam. MATERIALS AND METHODS: A total of 20 Swiss albino rats aged 6-7 weeks,
      of either sex, weighing about 100-150 g, were taken, and after acute toxicity
      studies two different doses were selected. The animals were divided into four
      different groups. The first group was kept as the control (normal saline), second
      as the standard (diazepam) and the remaining two groups as Test I and Test II,
      and given different doses of the AENOF. Skeletal muscle relaxant activity (motor
      coordination) on Rotarod and locomotor activity on photoactometer was performed.
      Statistical analysis was carried out by using analysis of variance, followed by
      Dunnett's multiple comparison tests. RESULTS: The result from the Actophotometer
      test and Rotarod test showed that the extract of AENOF significantly reduced (P <
      0.05) the motor coordination of the tested animals. CONCLUSIONS: Our data
      indicates that AENOF possesses skeletal muscle relaxant activities.

PMID- 26288475
TI  - Antioxidant, mutagenic, and antimutagenic activities of Tragopogon longirostis
      var. longirostis, an edible wild plant in Turkey.
AB  - OBJECTIVES: The ethanolic extract of Tragopogon longirostis var. longirostis, a
      wild edible plant in Anatolia was isolated, and its antioxidant, mutagenic, and
      antimutagenic properties were investigated. MATERIALS AND METHODS: The
      antioxidant activity (AA) was determined by the inhibition of 2,2-diphenyl-1
      picrylhydrazyl (DPPH) radical, total AA, and phenolic compounds. The mutagenic
      and antimutagenic activities were investigated by Ames Salmonella/microsome
      mutagenicity test. RESULTS: The IC50 value for DPPH radicals was 7.84 +/- 0.603
      mg/mL. The total AA increased with an increase in the concentration of the
      extracts (1, 5, 10, 20, and 30 mg/mL), containing linoleic acid emulsion. The
      total phenolic content was 284.71 +/- 5.6 mg gallic acid equivalent/g extract.
      The results showed that the ethanolic extract can be considered safe, because it
      does not have any mutagenic effect at the tested concentrations. As a result, the
      ethanolic extract of the leaves exhibited antimutagenic effects at 2.5, 0.25, and
      0.025 mg/plate concentrations. CONCLUSIONS: To our knowledge, this is the first
      study of the antioxidant, mutagenic, and antimutagenic activities of T.
      longirostis var. longirostis. These activities are an important topic in the food
      industry, as well as in the medical field.

PMID- 26288476
TI  - Calotropis procera: A potential cognition enhancer in scopolamine and
      electroconvulsive shock-induced amnesia in rats.
AB  - OBJECTIVES: Present study evaluates the effect of Calotropis procera
      (Apocynaceae) dry latex on cognitive function in rats using scopolamine and
      electroconvulsive shock (ECS) induced amnesia model. MATERIALS AND METHODS: Male
      Wistar rats were pretreated with 200, 400 and 800 mg/kg of C. procera dry latex
      in scopolamine-induced amnesia model. Dose showing maximum effect in cognitive
      performance was selected and further evaluated using scopolamine and ECS-induced
      amnesia model for its effect on neurochemical enzymes and cognitive performance.
      Acetylcholinesterase (AChE) activity, beta amyloid1-42, and dopamine level were
      analyzed, while the cognitive performance was assessed by elevated plus maze,
      step-through passive avoidance test, and Morris water maze. Simultaneously, C.
      procera dry latex (25, 50, 100, 250, 500, and 1000 MUg/mL) was screened for in
      vitro AChE inhibition assay. RESULTS: Pretreatment with (200, 400 and 800 mg/kg)
      C. procera dry latex shows dose dependent increase in cognitive performance in
      scopolamine-induced amnesia. Further, pretreatment with the selected dose (800
      mg/kg) showed significant improvement in transfer latency (P < 0.001, P < 0.01),
      escape latency (P < 0.05), time spent in target quadrant (P < 0.001) also
      significant decrease in AChE activity (P < 0.05), beta amyloid1-42 level (P <
      0.001), and increase in dopamine level (P < 0.01) in rat brain homogenate when
      compared with scopolamine and ECS disease control groups. IC50 for C. procera dry
      latex was found to be <1000 MUg/mL. CONCLUSIONS: Pretreatment with C. procera dry
      latex (800 mg/kg) produced significant cognition enhancement by improving
      cognitive performance and decreasing the marker neurochemical enzyme activity in
      scopolamine and ECS-induced amnesia model.

PMID- 26288477
TI  - In-vitro alpha-amylase and alpha-glucosidase inhibitory activity of Adiantum
      caudatum Linn. and Celosia argentea Linn. extracts and fractions.
AB  - OBJECTIVE: The objective of the present study was to provide an in-vitro evidence
      for the potential inhibitory activity of extracts and fractions of Adiantum
      caudatum Linn. and Celosia argentea Linn. on alpha-amylase and alpha-glucosidase
      enzymes. MATERIALS AND METHODS: The plant extracts were prepared, first with cold
      maceration (70% v/v ethanol) and then by Soxhlation techniques (95% v/v ethanol).
      Subsequently, the combined extracts were subjected for fractionation. Different
      concentrations (0.1, 0.2, 0.3, 0.4, and 0.5 mg/ml) of extract and fractions were
      subjected to alpha-amylase and alpha-glucosidase inhibitory assay. The absorbance
      was measured at 540 and 405 nm using multiplate reader and the percentage of
      alpha- amylase and alpha- glucosidase inhibitory activity and IC50 values of
      extract and fractions were calculated. RESULTS: Fraction 2 of A. caudatum and
      fraction 4 of C. argentea has shown highest alpha-amylase and alpha-glucosidase
      inhibitory potential with IC50 values of 0.241, 0.211 and 0.294, 0.249 mg/ml,
      respectively, which was comparable with acarbose (0.125 and 0.93 mg/ml). Whereas,
      extracts and remaining fractions of both the plants have shown lesser activity.
      CONCLUSION: The results of the present study indicate that, fraction 2 of A.
      caudatum, rich in triterpenoids and phenolics and fraction 4 of C. argentea, rich
      in flavonoids, are effective alpha- amylase and alpha- glucosidase inhibitors,
      which may be helpful to reduce the postprandial glucose levels. Hence, further
      studies may throw light on the antidiabetic potential of A. caudatum and C.
      argentea, especially in the management of type 2 diabetes.

PMID- 26288478
TI  - Short and long-term impact of pharmacovigilance training on the pharmacovigilance
      knowledge of medical students.
AB  - OBJECTIVES: The aim of this study was to evaluate the short and long-term impact
      of pharmacovigilance (PV) training on the 5th year medical students' knowledge
      about definitions and on the awareness of the regulatory aspects in PV. MATERIALS
      AND METHODS: In academic year 2010/11, the students completed structured,
      questionnaire before and just after training. They also completed the same
      questionnaire 1-year after the training. RESULTS: The students' knowledge about
      PV significantly increased after training in the short term (P < 0.001). However,
      the improvement decreased significantly in the long-term (P < 0.001). Although
      long-term scores were higher than the baseline score, the difference was not
      statistically significant. Total scores were 17.5 +/- 2.0, 20.8 +/- 2.0 and 18.0
      +/- 2.5; before, at short and long-term after the training. CONCLUSION: PV
      training increased the students' knowledge significantly. However, in the long
      term, the impact of the training is limited. Repeated training of PV should be
      planned.

PMID- 26288479
TI  - Nicotine quantity and packaging disclosure in smoked and smokeless tobacco
      products in India.
AB  - OBJECTIVES: A variety of smoked and smokeless tobacco products with varying
      nicotine content are accessible in India. Nicotine quantity in tobacco products
      has direct bearing on tobacco dependence. Our objective was to estimate nicotine
      content in various types of smoked and smokeless products. Disclosure for
      essential health warning was also checked. MATERIALS AND METHODS: Liquid-liquid
      extraction was used for nicotine extraction and high-performance thin layer
      chromatography technique was applied for quantification of nicotine in seventy
      one smoked and smokeless tobacco products. RESULTS: Significant variation in
      nicotine content was observed across products. In smoked tobacco, nicotine
      content varied from 1.01 to 13.0 mg/rod, while in smokeless tobacco products it
      ranged from 0.8 mg/g to 50.0 mg/g. Moisture content varied from 9% to 21%.
      CONCLUSION: This work lists a range of smoked and smokeless tobacco products
      available in this region. We report a wide variability in nicotine quantity
      across smoked and smokeless tobacco products. Such variation in nicotine content
      may have important implications for tobacco cessation interventions and policies.

PMID- 26288480
TI  - Dual inhibition of acetylcholinesterase and butyrylcholinesterase enzymes by
      allicin.
AB  - OBJECTIVES: The brain of mammals contains two major form of cholinesterase
      enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The dual
      inhibition of these enzymes is considered as a promising strategy for the
      treatment of neurological disorder such as Alzheimer's disease (AD), senile
      dementia, ataxia, and myasthenia gravis. The present study was undertaken to
      explore the anticholinesterase inhibition property of allicin. MATERIALS AND
      METHODS: An assessment of cholinesterase inhibition was carried out by Ellman's
      assay. RESULTS: The present study demonstrates allicin, a major ingredient of
      crushed garlic (Allium sativum L.) inhibited both AChE and BuChE enzymes in a
      concentration-dependent manner. For allicin, the IC50 concentration was 0.01
      mg/mL (61.62 MUM) for AChE and 0.05 +/- 0.018 mg/mL (308.12 MUM) for BuChE
      enzymes. CONCLUSIONS: Allicin shows a potential to ameliorate the decline of
      cognitive function and memory loss associated with AD by inhibiting
      cholinesterase enzymes and upregulate the levels of acetylcholine (ACh) in the
      brain. It can be used as a new lead to target AChE and BuChE to upregulate the
      level of ACh which will be useful in alleviating the symptoms associated with AD.

PMID- 26288481
TI  - Anti-inflammatory activity of Nerium indicum by inhibition of prostaglandin E2 in
      murine splenic lymphocytes.
AB  - OBJECTIVE: Nerium indicum Mill (syn. N. oleander L. and N. odorum Aiton; family:
      Apocynaceae) is a medicinal plant, used in the treatment of diverse ailments
      including various chronic inflammatory diseases in traditional medicine. We have
      previously demonstrated the immunomodulatory activity of a bioactive fraction of
      Nerium indicum leaf (NILE) by studying up-regulation of interleukin-2 (IL-2), IL
      10, interferon-gamma and down regulation of IL-4, tumor necrosis factor-alpha
      (TNF-alpha), nitric oxide, cyclooxygenase-1 (COX-1) and COX-2 activities.
      Therefore, this study aimed to confirm the anti-inflammatory activity of NILE by
      inhibition of prostaglandin E2 (PGE2) activity in murine splenic lymphocytes in
      vitro. MATERIALS AND METHODS: Murine lymphocytes were isolated from spleen and
      stimulated with 5 ?g/mL concanavalin A in RPMI-1640, supplemented with 50 U/mL
      penicillin, 50 U/mL streptomycin, 50 U/mL nystatin and 10% fetal bovine serum.
      Different concentrations (0-80 MUg/mL) of NILE were added and the cells were
      cultured for 48 h. The culture supernatants were thereafter collected by
      centrifugation and assayed for expression of PGE2 level. The data were analyzed
      statistically. RESULTS: The results demonstrated a 2.26-fold inhibition of PGE2
      level at 80 MUg/mL of NILE. Half maximum inhibitory concentration (IC50) was
      calculated to be 44.95 +/- 0.45 ?g/mL. Linear correlation analysis of the dose
      dependent PGE2 inhibition with other pro- and anti-inflammatory mediators
      demonstrated high inter-correlation between the parameters. CONCLUSIONS: Thus,
      the present study remains in accordance with our previous report and confirms the
      anti-inflammatory claim of N. indicum, mentioned in the traditional medicine.

PMID- 26288482
TI  - Pentazocine-induced contractures: Dilemma in management.
AB  - Pentazocine is a commonly used synthetic opioid analgesic for moderate to severe
      pain secondary to various conditions. Complications of parenteral opioid abuse
      including localized ulcerations, abscess, indurations, and sclerosis are well
      documented. We present a rare case of drug abuse due to pentazocine (Fortwin) in
      a 32-year-old female, who had severe myogenic contractures of her knee joints. 

PMID- 26288483
TI  - Ketamine-induced affective switch in a patient with treatment-resistant
      depression.
AB  - There is growing evidence to support the rapid, albeit short-lived antidepressant
      effect of subanesthetic dose of ketamine, a noncompetitive glutamate N-methyl-D
      aspartate receptor antagonist in treatment-resistant unipolar and bipolar
      depression. Ketamine is known to cause transient mood elevation or euphoria,
      psychotomimetic effects, and dissociative symptoms, but its use in unipolar or
      bipolar depression has not been reported to induce an affective switch amounting
      to persistent or prolonged hypomania/mania or manic-like syndrome. We report the
      case of a 52-year-old male with first episode, continuous, nonpsychotic,
      treatment-resistant, unipolar major depression of 10 years duration, who
      manifested a switch from depression to mania while being treated with
      subanesthetic dose of ketamine, given intramuscularly. This case suggests that
      polarity switch should be considered as a potential side effect while using
      ketamine for treatment-resistant depression. 

PMID- 26288484
TI  - Medication error report: Intrathecal administration of labetalol during obstetric
      anesthesia.
AB  - Labetalol, a combined alfa and beta-adrenergic receptor antagonist, is used as an
      antihypertensive drug. We report a case of an acute rise in blood pressure and
      lower limb pain due to the inadvertent intrathecal administration of labetalol,
      mistaking it for bupivacaine, during obstetric anesthesia. The situation was
      rescued by converting to general anesthesia. The cesarean delivery was
      uneventful, and mother as well as newborn child showed no ill-effect. This
      particular medication error was attributable to a failure on the part of the
      doctors administering the injection to read and cross-check medication labels and
      the practice of keeping multiple injections together. In the absence of an
      organized medication error reporting system and action on that basis, such events
      may recur in future. 

PMID- 26288485
TI  - Oxcarbazepine induced toxic epidermal necrolysis - a rare case report.
AB  - Carbamazepine, is well known to cause Stevens-Johnson syndrome and toxic
      epidermal necrolysis(TEN). Oxcarbazepine, a 10-keto analog of carbamazepine, is
      an anticholinergic, anticonvulsant and mood stabilizing drug, used primarily in
      the treatment of epilepsy. Its efficacy is similar to carbamazepine but allergic
      reactions and enzyme induction is low. We describe a case of oxcarbazepine
      induced TEN, who presented with erythematous ulcerative maculopapular rash. 

PMID- 26288487
TI  - Dealing with disasters: Need for awareness and preparedness.

PMID- 26288486
TI  - Nebivolol: A unique drug in acute and chronic renal disorders.

PMID- 26288488
TI  - Incidence of high altitude pulmonary edema in low-landers during re-exposure to
      high altitude after a sojourn in the plains.
AB  - BACKGROUND: There is uncertainty whether acclimatized low-landers who return to
      high altitude after a sojourn at low altitude have a higher incidence of
      pulmonary edema than during the first exposure to high altitude. METHODS: This
      was a prospective cohort study consisting of men ascending to 3400 m by road (N =
      1003) or by air (N = 4178). The study compared the incidence of high altitude
      pulmonary edema during first exposure vs the incidence during re-exposure in each
      of these cohorts. RESULTS: Pulmonary edema occurred in 13 of the 4178 entries by
      air (Incidence: 0.31%, 95% CI: 0.18%-0.53%). The incidence during first exposure
      was 0.18% (0.05%-0.66%) and 0.36% (0.2%-0.64%) during re-exposure (Fisher Exact
      Test for differences in the incidence (two-tailed) p = 0.534). The relative risk
      for the re-exposure cohort was 1.95 (95% CI, 0.43%-8.80%). Pulmonary edema
      occurred in 3 of the 1003 road entrants (Incidence: 0.30%, 95% CI: 0.08%-0.95%).
      All three cases occurred in the re-exposure cohort. CONCLUSION: The large overlap
      of confidence intervals between incidence during first exposure and re-exposure;
      the nature of the confidence interval of the relative risk; and the result of the
      Fisher exact test, all suggest that this difference in incidence could have
      occurred purely by chance. We did not find evidence for a significantly higher
      incidence of HAPE during re-entry to HA after a sojourn in the plains.

PMID- 26288489
TI  - Awareness about postpartum insertion of intrauterine device among antenatal
      cases.
AB  - BACKGROUND: In spite of many available contraceptives numerous unwanted and
      unplanned pregnancies occur. Though the couples desire contraception but are not
      able to accept it due to their ignorance and misconceptions. Intrauterine
      Contraceptive Device (IUCD); an effective contraceptive is usually inserted six
      weeks after delivery. It can be inserted within 48 h of delivery called
      postpartum insertion for which government has started the program in many states.
      The study was undertaken to find out the choices about contraception after
      delivery and awareness about postpartum insertion. METHODS: The present
      observational study was conducted in one of the zonal service hospitals. 500
      antenatal cases were included in the study. Their choice of contraception after
      delivery and awareness was determined through a questionnaire. Reasons for
      refusal of postpartum insertion were recorded. A small sample of staff also was
      included in the study. RESULTS: 500 cases were included in the study, a large
      number had decided about contraception; mainly breast feeding supplemented by
      barrier contraceptive. 94 of 500 were willing for insertion of contraceptive
      device but not immediately after delivery due to apprehension in general and fear
      of side effects. Staff's awareness about postpartum insertion was poor.
      CONCLUSION: Knowledge and acceptance of postpartum insertion is very low among
      antenatal women; probably because the concept is new in the community. There is a
      strong need to increase the knowledge and awareness about this by health
      education and counseling.

PMID- 26288490
TI  - Distribution of hepatitis B virus genotype and cancer predicting precore and
      basal core promoter mutations.
AB  - BACKGROUND: Chronic hepatitis B (CHB) infection which is associated with an
      increased risk of developing liver disease including cirrhosis and hepatocellular
      carcinoma. Viral factors that may increase the risk for HCC development include
      HBV DNA level, genotypes, and naturally occurring mutations such as hepatitis B
      virus precore (PC) (G1896A) and basal core promoter (BCP) A1762T/G1764A double
      mutations. HBV genotypes and subgenotypes can significantly influence HBeAg
      seroconversion rates, viremia levels, mutational patterns that could
      significantly influence the heterogeneity in clinical manifestations and even
      response to antiviral therapy. METHOD: 94 CHB infected individuals with
      detectable serum HBV DNA levels were studied. HBsAg, HBeAg, anti-HBc IgM antibody
      estimations were done by ELISA. HBV DNA estimation was done. The HBV genotypes
      were determined by TSP-PCR and 10 samples randomly selected for DNA sequencing.
      PC and BCP mutations were determined by DNA sequence analysis of core region.
      RESULT: Of 94 study participant samples with detectable serum HBV DNA levels, 75
      were successfully genotyped and sequenced for BCP/PC region. 30/75 (40%) harbored
      PC and BCP mutations. The total Double mutations of BCP at A1762T/G1764A
      nucleotide positions, and PC mutation at G1896A nucleotide position were seen in
      29.3% and 21.3%, respectively. All 75 isolates were subtype D using TSP-PCR.
      However, by sequencing 2/10 were subtype A, while 8 were subtype D. CONCLUSION:
      Our study reinforces that D is the predominant genotype in Indian population. It
      reveals that Indian CHB subjects have increased prevalence of BCP & PC mutations,
      which possibly may lead to development of HCC.

PMID- 26288491
TI  - Uterine artery embolisation for uterine fibroids: Our experience at a tertiary
      care service hospital.
AB  - BACKGROUND: Uterine artery embolisation (UAE) has evolved as a minimally invasive
      and effective alternative, treatment modality for women with symptomatic
      fibroids. We discuss our initial experience of UAE in the management of
      symptomatic fibroids. METHODS: Twenty five symptomatic patients of uterine
      fibroids were treated with UAE by selectively cannulating and injecting poly
      vinyl alcohol particles into the uterine arteries. Post treatment follow up was
      done at 2 and 6 months respectively. RESULTS: Pre-treatment, the sizes of
      fibroids were between 3.9 and 10.9 cm (mean 7.4) on ultrasonography. Of the total
      25 patients, 49 uterine arteries were embolised with a technical success rate of
      98%. Menorrhagia persisted in 7 patients, dysmenorrhea in 4 patients and pressure
      symptoms in 2 patients respectively in follow up study of six months which
      corresponds to a reduction in symptoms by 68% for menorrhagia, 71% for
      dysmenorhoea and 75% for those with pressure symptoms respectively. At 2 months
      follow-up post embolisation, the mean diameter of the fibroid was 4.03 cm (range
      2-5.2 cm) and at 6 months 3.2 cm (range 1.3-4.1 cm), corresponding to size
      reduction of 45.5% and 57%, respectively. Follow up with ultrasonography at 2 and
      6 months period showed successful fibroid reduction in 24 patients with
      corresponding reduction in the symptomatology. One patient remained symptomatic
      with increase in fibroid size and had to undergo hysterectomy. CONCLUSION:
      Uterine artery embolisation can be considered as an alternative to hysterectomy
      in appropriately selected symptomatic patients of uterine fibroids.

PMID- 26288492
TI  - Comparative study of anatomical specimens using plastination by araldite HY103,
      polypropylene resin, 6170H19 Orthocryl and silicone - A qualitative study.
AB  - BACKGROUND: Most of the organs and tissues are preserved in formalin with its own
      set of disadvantages. Plastination is a unique method of permanently preserving
      tissue in a life like state. Plastination developed by western authorities is a
      labour and equipment intensive affair. Most common polymer used is S10, however
      this study uses easily available alternative polymers for plastination. METHOD:
      Various polymers like Epoxy resins, Polypropylene resins, Orthocryl and silicone
      were used in plastinating the anatomical specimens. Specific methods were used
      for solid, hollow organs and brain specimens. The specimens were made to undergo
      stages of fixation, dehydration, impregnation and curing. The results were
      studied and interpreted under various parameters. RESULTS: The results were
      interpreted under various parameters like shrinkage, retention of colour, odour,
      pliability and retention of gross anatomy. The study concluded that Orthocryl and
      Epoxy resins retained maximum colour with minimal shrinkage while maximum
      discolouration was with polypropylene plastinates. Brain sections were best
      preserved in Orthocryl. CONCLUSION: The study concluded that indigenous methods
      and materials can produce quality plastinates which can be an important adjunct
      to traditional methods of teaching however more studies need to be done for
      refinement.

PMID- 26288493
TI  - Prevalence of molecular subtypes of invasive breast cancer: A retrospective
      study.
AB  - BACKGROUND: Classification of breast cancers into different molecular subtypes
      using immunohistochemistry as a surrogate tool to DNA microarray technology has
      been identified. Aim of this study was to find the precise prevalence of
      molecular subtypes of invasive breast carcinoma using immunohistochemistry and to
      correlate it with histological and clinical prognostic factors. METHODS: A
      descriptive study design wherein 56 breast carcinoma cases diagnosed between May
      2012 and Apr 2014 were reviewed and molecular subtyped using relevant
      immunohistochemical markers. Age, histological type, tumor size, tumor grade,
      lymphovascular emboli (LVE), nodal status and basal marker expressions were
      analyzed for all cases. Correlations between molecular subtypes and clinico
      pathological characteristics were evaluated statistically. RESULTS: In our study
      group, average age of patients was 50.5 years and most of patients were diagnosed
      in stage II (54%). Luminal A subtype was most prevalent 34%, followed by Basal
      like/Triple negative subtype 25%. Luminal B and Her2/neu subtypes had same
      prevalence i.e. 18% each and Breast Tissue like/Unclassified subtype/Penta
      Negative subtype was 5%. All cases demonstrated positivity for the luminal
      cytokeratins 8/18. Histological grade and ER negative status showed strong
      correlations with basal markers. CONCLUSION: On the basis of hormone receptor,
      Her2 neu, EGFR and CK 5/6 expressions, breast carcinoma cases were classified
      into five distinct molecular subtypes which show significant differences in
      regards to morphological features, prognostic markers and there by predicting
      possible clinical outcome.

PMID- 26288494
TI  - Clinical evaluation of the fiber post and direct composite resin restoration for
      fixed single crowns on endodontically treated teeth.
AB  - BACKGROUND: The restoration of an endodontically treated fractured tooth has been
      a challenge for restorative dentists for decades. The performance of fiber posts
      when used in conjunction with direct composite resin restorations have been
      largely unreported. This study was conducted with the aim of evaluating the
      survival rate of endodontically treated teeth restored with adhesive bonded fiber
      reinforced resin posts and direct composite core with additional crown coverage.
      METHODS: Sixty patients who required endodontic treatment with post core crown
      were selected from outpatient department of Air Force Institute of Dental
      Sciences, Bangalore. Sixty-four teeth were endodontically treated and restored
      with fiber post and direct resin composite core restoration. Patients were
      evaluated immediately after restoration and reevaluated at the end of first,
      second and third months. After 3 months of clinical evaluation, if teeth were
      asymptomatic they were restored with complete coverage porcelain fused to metal
      restorations and evaluated immediately, and again reevaluated at the end of
      first, third, and sixth months. RESULTS: After 3 months of clinical evaluation,
      only two teeth exhibited periapical lesion with clinical symptoms and three teeth
      without any clinical symptoms. Five teeth exhibited slight marginal staining,
      three teeth showed partial loss of restoration, and two teeth exhibited complete
      loss of restoration with the fracture of the post. At the end of sixth month
      after restoration with full coverage crown, two teeth had dislodged restoration
      due to fracture of post and two teeth exhibited displacement of the post.
      CONCLUSION: Fiber posts are the best alternative for restoration of fractured
      endodontically treated teeth. Fiber posts and direct composite resin core
      materials are strongly recommended for restoration of endodontically treated
      mutilated teeth among the dental establishments of Armed Forces.

PMID- 26288495
TI  - A longitudinal study to determine association of various maternal factors with
      neonatal birth weight at a tertiary care hospital.
AB  - BACKGROUND: Neonatal birth weight is a powerful predictor of infant growth and
      survival and maternal factors like poor knowledge and insufficient dietary intake
      are significant risk factors. Other preventable determinants like pre pregnant
      BMI <18.5, low gestational weight gain (GWG) and anemia are also associated with
      low birth weight. This study was carried out to identify the impact of these
      maternal factors with risk of low birth weight (LBW). METHODS: A longitudinal
      study was carried out on 124 booked antenatal cases at a tertiary care center. A
      validated protocol containing socio demography, food frequency and anthropometry
      was administered at the 3rd trimester. Birth weight of the newborn was noted
      after delivery. RESULTS: 26.28% children had low birth weight (<2500 g), 14.6%
      mothers were thin (BMI < 18.5), 55.3% mothers had a weight gain of less than 9
      kgs and 45.5% were anemic. 81.81% mothers with BMI >18.5 and 28.92% women who
      were educated till high school had a baby with LBW. Most mothers consumed milk
      and vegetables daily and a few consumed non vegetarian foods but quality and
      quantity of food were grossly inadequate. GWG levels and Hb levels were
      significantly different in different birth weight groups and also were
      significantly associated with low birth weight. CONCLUSION: Quality and quantity
      of maternal dietary intake during pregnancy, even in normal weight mothers (BMI >
      18.5), are important determinants of birth weight. Nutritional counseling for
      mothers during the antenatal period is the cornerstone for healthy mother and
      healthy child.

PMID- 26288496
TI  - Dehydroepiandrosterone: A panacea for the ageing ovary?
AB  - Considerable improvements and advancements have been made in the treatment of
      infertility but poor ovarian reserve whether due to prematurely or a
      physiologically ageing ovary, continues to be one of the few unresolved problems
      of modern infertility care. Fertility researchers had been active for quite some
      time to find a way to help reverse the effects of ageing on the ovaries but none
      made an impact till the introduction of Dehydroepiandrosterone [DHEA]. DHEA a
      mild, and therapeutically well tolerated, male hormone has emerged as a real
      potential candidate to reverse the effects of ageing on ovaries. Apart from this,
      DHEA has also been postulated to improve egg and embryo quality, pregnancy rates
      and time to conception and reduces miscarriage rates. This review attempts to
      highlight the mechanism of action of this drug, its indications and its current
      status for treating women with decreased ovarian reserve. 

PMID- 26288497
TI  - Kumbh Mela 2013: Healthcare for the millions.
AB  - Mass gatherings pose challenges to healthcare systems anywhere in the world. The
      Kumbh Mela 2013 at Allahabad, India was the largest gathering of humanity in the
      history of mankind, and posed an exciting challenge to the provision of
      healthcare services. At the finale of the Mela, it was estimated that about 120
      million pilgrims had visited the site. Equitable geospatial distribution of adhoc
      health care facilities were created on a standardised template with integrated
      planning of evacuation modalities. Innovative and low cost response measures for
      disaster mitigation were implemented. Emergency patient management kits were
      prepared and stocked across the health care facilities for crisis response.
      Dynamic resource allocation (in terms of manpower and supplies) based on patient
      volumes was done on a daily basis, in response to feedback. An adhoc mega
      township created on the banks of a perennial river (Ganga) in the Indian
      subcontinent for accommodating millions of Hindu pilgrims. Conventional mindset
      of merely providing limited and static healthcare through adhoc facilities was
      done away with. Innovative concepts such as riverine ambulances and disaster kits
      were introduced. Managing the medical aspects of a mass gathering mega event
      requires allocation of adequate funds, proactive and integrated medical planning
      and preparedness. 

PMID- 26288498
TI  - Multiresistant Elizabethkingia meningoseptica infections in tertiary care.

PMID- 26288499
TI  - Sterile corneal perforations in a case of severe dry eyes.

PMID- 26288500
TI  - Vertebral intraosseous lipoma.

PMID- 26288501
TI  - Nattrassia mangiferae: An uncommon agent of onychomycosis.

PMID- 26288502
TI  - Predatory publishing: Writers beware!

PMID- 26288503
TI  - Letter to Editor.

PMID- 26288504
TI  - Reply.

PMID- 26288505
TI  - Letter to the Editor.

PMID- 26288506
TI  - Letter to Editor.

PMID- 26288507
TI  - Reply.

PMID- 26288508
TI  - Reply.

PMID- 26288509
TI  - Human papillomavirus detection in genital samples by novel PGMY Primers.

PMID- 26288510
TI  - Reply.

PMID- 26288511
TI  - Letter to the Editor.

PMID- 26288512
TI  - Reply.

PMID- 26288513
TI  - Reviewing the review.

PMID- 26288514
TI  - Chest tuberculosis: Radiological review and imaging recommendations.
AB  - Chest tuberculosis (CTB) is a widespread problem, especially in our country where
      it is one of the leading causes of mortality. The article reviews the imaging
      findings in CTB on various modalities. We also attempt to categorize the findings
      into those definitive for active TB, indeterminate for disease activity, and
      those indicating healed TB. Though various radiological modalities are widely
      used in evaluation of such patients, no imaging guidelines exist for the use of
      these modalities in diagnosis and follow-up. Consequently, imaging is not
      optimally utilized and patients are often unnecessarily subjected to repeated CT
      examinations, which is undesirable. Based on the available literature and our
      experience, we propose certain recommendations delineating the role of imaging in
      the diagnosis and follow-up of such patients. The authors recognize that this is
      an evolving field and there may be future revisions depending on emergence of new
      evidence. 

PMID- 26288515
TI  - Blunt traumatic diaphragmatic hernia: Pictorial review of CT signs.
AB  - Blunt diaphragmatic rupture rarely accounts for immediate mortality and may go
      clinically silent until complications occur which can be life threatening.
      Although many imaging techniques have proven useful for the diagnosis of blunt
      diaphragmatic rupture, multidetector CT (MDCT) is considered to be the reference
      standard for the diagnosis of diaphragmatic injury. Numerous CT signs indicating
      blunt diaphragmatic rupture have been described in literature with variable
      significance. Accurate diagnosis depends upon the analysis of all the signs
      rather than a single sign; however, the presence of blunt diaphragmatic rupture
      should be considered in the presence of any of the described signs. We present a
      pictorial review of various CT signs used to diagnose blunt diaphragmatic injury.
      Multiplanar reconstruction is very useful; however, predominantly axial sections
      have been described in this pictorial review as the images shown are from dual
      slice CT. 

PMID- 26288516
TI  - Endovascular treatment of thrombosed inferior vena cava filters: Techniques and
      short-term outcomes.
AB  - PURPOSE: To present the techniques for endovascular treatment of thrombosed
      filter-bearing inferior vena cavae (IVCs), along with short-term clinical and
      imaging follow-up. MATERIALS AND METHODS: A total of 45 consecutive patients (17
      females and 28 males), aged 19-79 years (mean age of 49 years), who had IVC
      filter placement complicated by symptomatic acute or chronic iliocaval thrombosis
      and underwent endovascular therapy were studied. All patients presented with
      lower extremity swelling and/or pain. One patient also had bilateral lower
      extremity swelling and chronic gastrointestinal (GI) bleeding which was secondary
      to chronic systemic to portal venous collaterals. Patients underwent one or more
      of the following endovascular treatments depending on the chronicity and extent
      of thrombosis: (a) catheter-directed thrombolysis (CDT) (n = 25), (b)
      pharmacomechanical thrombolysis (PMT) (n = 15), (c) balloon angioplasty (n = 45),
      and/or (d) stent placement across the filter (n = 42). In addition, 16 patients
      underwent groin arteriovenous fistula (AVF) creation (36%) and 3 (7%) had femoral
      venous thrombectomy to improve flow in the recanalized iliac veins and IVCs.
      RESULTS: Anatomical success was achieved in all patients. Follow-up was not
      available in 10 patients (lost to follow-up, n = 4; expired due to comorbidities,
      n = 2; lost to follow-up after re-intervention, n = 4). At a mean follow-up time
      of 13.3 months (range 1-48 months), clinical success was achieved in 27 patients
      (60%), i.e. in 21 patients without re-intervention and in 6 patients with re
      intervention. Clinical success was not achieved despite re-intervention in eight
      patients. Higher clinical success was noted in patients who did not require
      repeat interventions (P = 0.03) and the time to re-intervention was significantly
      shorter in patients who had clinical failure (P = 0.01). AVF creation did not
      improve the clinical success rate (P = 1). There was no significant difference in
      clinical success between patients who had acute or subacute thrombosis compared
      to those who had chronically occluded filter-bearing IVCs (P = 1). CONCLUSION:
      This study suggests that endovascular therapy for thrombosed filter-bearing IVCs
      is safe and technically feasible.

PMID- 26288517
TI  - Endovascular treatment of isolated arterial pulmonary malinosculation.
AB  - We report the endovascular management of a series of four cases of isolated
      systemic supply to normal lung or isolated arterial pulmonary malinosculation of
      the left lung. In these cases, the basal segments of the left lung lacked normal
      pulmonary arterial supply and instead received systemic arterial blood from the
      descending thoracic aorta. The relevant anatomy and literature are also reviewed.

PMID- 26288518
TI  - USG-guided needle-directed pulse-spray pharmaco-mechanical thrombolysis of
      hemodialysis grafts/fistula: A novel technique.
AB  - The incidence of end-stage renal disease is significantly increasing and most
      patients who require renal transplantation are undergoing hemodialysis through
      tunneled/non-tunneled dialysis catheters and arteriovenous fistulas. The greatest
      disadvantage of the hemodialysis access is the limited durability of the
      arteriovenous fistulas and grafts, which, on average, remain patent for <3 years,
      but are the lifeline for hemodialysis patients. Catheter-directed interventions
      are successful in re-establishing flow in more than 80% of thrombosed
      hemodialysis fistulas and have become the treatment of choice for failing or
      thrombosed accesses. However, these interventions are expensive and require a
      tertiary center with well-equipped labs. The novel technique of needle-directed
      thrombolysis is less expensive and can be done on an OPD basis in any primary
      healthcare setup. To the extent we have searched, no such technique has been
      published so far in the English literature. 

PMID- 26288520
TI  - Osteoid osteoma masquerading tubercular arthritis or osteomyelitis on MRI: Case
      series and review of literature.
AB  - Magnetic resonance imaging (MRI) scans for osteoid osteoma could be misleading
      and can be misinterpreted as tuberculosis, especially when used as the principal
      modality of investigation. We retrospectively reviewed cases presenting to our
      institute for second opinion and selected six cases that were referred to our
      institute with a provisional diagnosis of tubercular arthritis or osteomyelitis
      and were identified to have osteoid osteoma. We reviewed the literature on
      typical and atypical clinical and radiological presentations of osteoid osteoma
      depending upon their location and present radiological features on MRI that
      should alert the radiologists toward a correct diagnosis. 

PMID- 26288521
TI  - Evaluation of static and dynamic MRI for assessing response of bone sarcomas to
      preoperative chemotherapy: Correlation with histological necrosis.
AB  - OBJECTIVES: Preoperative chemotherapy plays a key role in management of bone
      sarcomas. Postoperative evaluation of histological necrosis has been the gold
      standard method of assessing response to preoperative chemotherapy. This study
      was done to evaluate the efficacy of static and dynamic magnetic resonance
      imaging (MRI) for assessing response preoperatively. MATERIALS AND METHODS: Our
      study included 14 patients (12 osteosarcomas and 2 malignant fibrous
      histiocytomas) with mean age of 21.8 years, treated with preoperative
      chemotherapy followed by surgery. They were evaluated with static and dynamic MRI
      twice, before starting chemotherapy and again prior to surgery. Change in tumor
      volume and slope of signal intensity - time curve were calculated and correlated
      with percentage of histological necrosis using Pearson correlation test. RESULTS:
      The change in dynamic MRI slope was significant (P = 0.001). Also, >=60%
      reduction in slope of the curve proved to be an indicator of good histological
      response [positive predictive value (PPV) =80%]. Change in tumor volume failed to
      show significant correlation (P = 0.071). Although it showed high negative
      predictive value (NPV = 85.7%), PPV was too low (PPV = 57.14%). CONCLUSIONS:
      Dynamic MRI correctly predicts histological necrosis after administration of
      preoperative chemotherapy to bone sarcomas. Hence, it can be used as a
      preoperative indicator of response to neoadjuvant chemotherapy. On the other
      hand, volumetric assessment by static MRI is not an effective predictor of
      histological necrosis. This study proves the superiority of dynamic contrast
      enhanced study over volumetric study by MRI.

PMID- 26288522
TI  - Carpal boss in chronic wrist pain and its association with partial osseous
      coalition and osteoarthritis - A case report with focus on MRI findings.
AB  - The carpal boss is a bony prominence at the dorsal aspect of the 2(nd) and/or
      3(rd) carpometacarpal joint, which has been linked to various etiologies,
      including trauma, os styloideum, osteophyte formation, and partial osseous
      coalition. It may result in symptoms through secondary degeneration, ganglion
      formation, bursitis, or extensor tendon abnormalities by altered biomechanics of
      wrist motion. We present a case of symptomatic carpal boss with the finding of a
      partial osseous coalition at the 2(nd) carpometacarpal (metacarpal-trapezoid)
      joint and highlight the magnetic resonance imaging (MRI) findings of carpal boss
      impingement and secondary osteoarthritis. To the best of our knowledge, there is
      no report in the literature describing the imaging findings of partial osseous
      coalition and degenerative osteoarthritis in relation to carpal boss. 

PMID- 26288519
TI  - Perspectives in ultrasound-guided musculoskeletal interventions.
AB  - Ultrasonography (USG) is a safe, easily available, and cost-effective modality,
      which has the additional advantage of being real time for imaging and image
      guided interventions of the musculoskeletal system. Musculoskeletal interventions
      are gaining popularity in sports and rehabilitation for rapid healing of muscle
      and tendon injuries in professional athletes, healing of chronic tendinopathies,
      aspiration of joint effusions, periarticular bursae and ganglia, and perineural
      injections in acute and chronic pain syndromes. This article aims to provide an
      overview of the spectrum of musculoskeletal interventions that can be done under
      USG guidance both for diagnostic and therapeutic purposes. 

PMID- 26288523
TI  - Polyostotic fibrous dysplasia associated with intramuscular myxomas: Mazabraud
      syndrome.
AB  - The authors report a new case of Mazabraud syndrome in a 69-year-old woman
      complaining of pain in her right thigh. Plain radiographs demonstrated
      radiological findings consistent with polyostotic fibrous dysplasia of the right
      femur and tibia. Magnetic resonance imaging (MRI) study showed soft tissue tumors
      located in the vastus intermedius muscle with typical signal features of
      intramuscular myxomas. Biopsy was not performed because of its benign nature.
      Symptomatic treatment was prescribed and all the lesions remained 1 year after
      the diagnosis. 

PMID- 26288524
TI  - A rare case of extra nodal Rosai-Dorfman disease with isolated multifocal osseous
      manifestation.
AB  - Sinus histiocytosis with massive lymphadenopathy (SHML) or Rosai-Dorfman disease
      is a non-neoplastic condition which typically presents as massive, bilateral
      cervical lymphadenopathy and can involve multiple extranodal organ systems such
      as skin, eyes, and upper respiratory tract in about 28% cases. Bone lesions in
      association with nodal disease are seen in less than 10% cases. Isolated bone
      involvement as the only manifestation of SHML is extremely rare, with less than
      50 cases reported in the literature. We report a very uncommon case of Rosai
      Dorfman disease with isolated multifocal osseous involvement as the only
      presenting feature, involving about 10 different sites with no lymphadenopathy or
      other organ system involvement. 

PMID- 26288525
TI  - Primary versus secondary achalasia: New signs on barium esophagogram.
AB  - AIM: To investigate new signs on barium swallow that can differentiate primary
      from secondary achalasia. MATERIALS AND METHODS: Records of 30 patients with
      primary achalasia and 17 patients with secondary achalasia were reviewed.
      Clinical, endoscopic, and manometric data was recorded. Barium esophagograms were
      evaluated for peristalsis and morphology of distal esophageal segment (length,
      symmetry, nodularity, shouldering, filling defects, and "tram-track sign").
      RESULTS: Mean age at presentation was 39 years in primary achalasia and 49 years
      in secondary achalasia. The mean duration of symptoms was 3.5 years in primary
      achalasia and 3 months in secondary achalasia. False-negative endoscopic results
      were noted in the first instance in five patients. In the secondary achalasia
      group, five patients had distal esophageal segment morphology indistinguishable
      from that of primary achalasia. None of the patients with primary achalasia and
      35% patients with secondary achalasia had a length of the distal segment
      approaching combined height of two vertebral bodies. None of the patients with
      secondary achalasia and 34% patients with primary achalasia had maximum caliber
      of esophagus approaching combined height of two vertebral bodies. Tertiary
      contractions were noted in 90% patients with primary achalasia and 24% patients
      with secondary achalasia. Tram-track sign was found in 55% patients with primary
      achalasia. Filling defects in the distal esophageal segment were noted in 94%
      patients with secondary achalasia. CONCLUSION: Length of distal esophageal
      segment, tertiary contractions, tram-track sign, and filling defects in distal
      esophageal segment are useful esophagographic features distinguishing primary
      from secondary achalasia.

PMID- 26288526
TI  - Pediatric multifocal liver lesions evaluated by MRI.
AB  - OBJECTIVE: The purpose of this study is to present our experience with MRI
      evaluation of multifocal liver lesions in children and describe the MRI
      characteristics of these lesions. PATIENTS AND METHODS: A retrospective review of
      consecutive MRI exams performed for the evaluation of multiple liver lesions
      between 1 January 2007 and 31 December 2012 was done to note the number of
      lesions, the size of the largest lesion, MR signal characteristics, and
      background liver. Final diagnosis was assigned to each case based on pathology in
      the available cases and a combination of clinical features, imaging features, and
      follow-up in the remaining cases. RESULTS: A total of 48 children (22 boys, 26
      girls; age between 3 months and 18 years with average age 10.58 years and median
      age 11 years) were included in the study. Totally 51 lesion diagnoses were seen
      in 48 children that included 17 focal nodular hyperplasia (FNH), 8 hemangiomas, 7
      metastases, 6 regenerative nodules, 3 adenomas, 3 abscesses, and one each of
      angiomyolipoma, epithelioid hemangioendothelioma, focal fatty infiltration,
      hepatocellular carcinoma, hepatic infarction, nodular regenerative hyperplasia,
      and hepatic cyst. Background liver was normal in 33, cirrhotic in 10, fatty in 3,
      and siderotic in 2 children. Most FNH, hemangiomas, and regenerative nodules
      showed characteristic MRI features, while metastases were variable in signal
      pattern. CONCLUSION: Many commonly seen multifocal liver lesions in children have
      characteristic MRI features. MRI can help to arrive at reasonable differential
      diagnoses for multifocal liver lesions in children and guide further
      investigation and management.

PMID- 26288527
TI  - Clinicoradiological appraisal of 'paraduodenal pancreatitis': Pancreatitis
      outside the pancreas!
AB  - PURPOSE: Paraduodenal pancreatitis (PP) is a unique form of focal chronic
      pancreatitis that selectively involves the duodenum and aberrant pancreatic
      tissue located near the minor papilla (beyond the pancreas proper). The
      pseudotumoral nature of the disease often generates considerable clinical
      quandary and patient apprehension, and therefore merits a better understanding.
      The present study appraises the clinicoradiological manifestations of PP in 33
      patients. MATERIALS AND METHODS: Clinical, laboratory, and radiological
      manifestations of 33 patients of PP treated in gastroenterology/hepatology and
      hepato-pancreatico-biliary surgery units during June 2010-August 2014 were
      retrospectively reviewed. RESULTS: All patients were young to middle-aged men
      (100%) with history of alcohol abuse (93.9%) and/or smoking (42.4%), who
      presented either with acute or gradually worsening abdominal pain (90.9%).
      Pancreatic enzymes and serum tumor markers remained normal or were
      mildly/transiently elevated. Cystic variant was detected in 57.6% (solid in
      42.4%); the disease remained confined to the groove/duodenum (pure form) in
      45.4%. Medial duodenal wall thickening with increased enhancement was seen in
      87.87 and 81.81%, respectively, and duodenal/paraduodenal cysts were seen in
      78.78%. Pancreatic calcifications and biliary stricture were seen 27.3% patients.
      Peripancreatic arteries were neither infiltrated nor encased. CONCLUSION: PP has
      a discrete predilection for middle-aged men with history of longstanding alcohol
      abuse and/or smoking. Distinguishing imaging findings include thickening of the
      pancreatic side of duodenum exhibiting increased enhancement with
      intramural/paraduodenal cysts. This may be accompanied by plate-like scar tissue
      in the groove region, which may simulate groove pancreatic carcinoma. However, as
      opposed to carcinoma, the peripancreatic arteries are neither infiltrated nor
      encased, rather are medially displaced.

PMID- 26288528
TI  - Choledochal cyst of the cystic duct: Report of imaging findings in three cases
      and review of literature.
AB  - The choledochal cysts, which refer to the cystic dilatation of the biliary duct,
      are rare lesions generally seen in children. Choledochal cyst of the cystic duct
      is an uncommon entity. Often, it is associated with the choledochal cyst of the
      rest of the biliary tree. Isolated cystic duct choledochal cyst is quite rare.
      Most of these lesions have been recognized only on surgery. Modern cross
      sectional imaging methods have facilitated preoperative recognition and
      characterization of cystic duct cyst enabling formulation of appropriate
      management strategy. We report the imaging findings in three cases of choledochal
      cyst involving the cystic duct. All these cases were correctly diagnosed
      preoperatively. A review of cases reported in the literature and the role of
      imaging in guiding the management are also presented. 

PMID- 26288529
TI  - Comment on: Fetal gastric pseudomass at 30 weeks of gestation and its regression
      after 17 days of birth.

PMID- 26288530
TI  - Authors reply.

PMID- 26288531
TI  - Mimics of bone tumors.

PMID- 26288532
TI  - The Stall Grid Contest.

PMID- 26288533
TI  - Multidetector CT angiography in evaluation of prospective renal donors.

PMID- 26288534
TI  - Erratum: Morphometric analysis of diameter and relationship of vertebral artery
      with respect to transverse foramen in Indian population: Erratum.
AB  - [This corrects the article on p. 167 in vol. 25, PMID: 25969640.]. 

PMID- 26288535
TI  - Difference in clinical outcome between total shoulder arthroplasty and reverse
      shoulder arthroplasty used in hemiarthroplasty revision surgery.
AB  - INTRODUCTION: The increase of shoulder replacements will lead to a higher
      revision rate of shoulder arthroplasties. The aim of this study is to evaluate
      the clinical results of revision surgery performed in our hospital, distinguish
      the differences in clinical outcome according to revision indication and
      differences between total shoulder arthroplasty (TSA) and reverse shoulder
      arthroplasty (RSA) in hemiarthroplasty (HA) revision surgery. MATERIALS AND
      METHODS: All patients with an indication for revision of HA were retrospectively
      included. Clinical evaluation consisted of pre- and post-operative constant
      scores, disability of arm-shoulder-hand-score (DASH), Dutch translation of the
      simple shoulder test ((D)SST), Oxford shoulder score test (OSS), short form (SF
      36) and the complication rate. RESULTS: From July 1994 to July 2008, 39 patients
      (40 shoulders) underwent revision arthroplasty. Of 19 patients (19 shoulders) we
      obtained a complete follow-up. The mean age at revision surgery 69 +/- 10 years
      (range: 46-83) and the mean follow-up 41 +/- 31 months (range: 10-113). In 7
      cases TSA was used for revision when the cuff was intact, 12 times RSA was
      performed. The indications for the revision were glenoid erosion (n = 4), humeral
      component malposition (n = 2), cuff-pathology (n = 12) and infection (n = 1).
      Postoperative constant score 51.7 +/- 11.4 for TSA and 31.1 +/- 18.7 for RSA (P =
      0.008). The DASH was 48.3 +/- 25.1 and 68.7 +/- 17.5, respectively (P = 0.09).
      DSST showed 6 +/- 4 and 4 +/- 4 (P = 0.414). OSS 41.3 +/- 10.1 and 28.1 +/- 10.3
      (P = 0.017). SF-36 43.3 +/- 22.1 and 24.5 +/- 12.8 (P = 0.072). Four shoulders
      (21%) presented four complications. CONCLUSIONS: In this study, revision surgery
      showed poor to reasonable postoperative results and better clinical outcome for
      TSA. When a revision after HA was needed, and the soft-tissue component of the
      shoulder was intact, a TSA proved to be a preferable solution.

PMID- 26288536
TI  - Arthroscopic repair of type II SLAP lesions: Clinical and anatomic follow-up.
AB  - AIMS: The aim was to evaluate the clinical and anatomic outcome of arthroscopic
      repair of type II SLAP lesions. MATERIALS AND METHODS: The senior author
      performed isolated repairs of 25 type II SLAP lesions in 25 patients with a mean
      age of 40.0 +/- 12 years. All tears were repaired using standard arthroscopic
      suture anchor repair to bone. All patients were reviewed using a standardized
      clinical examination by a blinded, independent observer, and using several
      shoulder outcome measures. Patients were evaluated by magnetic resonance imaging
      arthrogram at a minimum of 1-year postoperatively. STATISTICAL ANALYSIS USED: Two
      tailed paired t-test were used to determine significant differences in
      preoperative and postoperative clinical outcomes scores. In addition, a Fisher's
      exact test was used. RESULTS: At a mean follow-up of 54-month, the mean American
      Shoulder and Elbow Surgeons Shoulder Index (ASES) scores improved from 52.1
      preoperatively to 86.1 postoperatively (P < 0.0001) and the Simple Shoulder Test
      (SST) scores from 7.7 to 10.6 (P < 0.0002). Twenty-two out of the 25 patients
      (88%) stated that they would have surgery again. Of the 21 patients who had
      postoperative magnetic resonance imaging arthrographys (MRAs), 9 patients (43%)
      demonstrated dye tracking between the labrum bone interface suggestive of a
      recurrent tear and 12 patients (57%) had a completely intact repair. There was no
      significant difference in ASES, SST, and patient satisfaction scores in patients
      with recurrent or intact repairs. CONCLUSIONS: Arthroscopic repair of type II
      SLAP lesions demonstrated improvements in clinical outcomes. However, MRA imaging
      demonstrated 43% of patients with recurrent tears. MRA results do not necessarily
      correlate with clinical outcome.

PMID- 26288537
TI  - Triple labrum tears repaired with the JuggerKnotTM soft anchor: Technique and
      results.
AB  - PURPOSE: The 2-year outcomes of patients undergoing repair of triple labrum tears
      using an all-suture anchor device were assessed. MATERIALS AND METHODS: Eighteen
      patients (17 male, one female; mean age 36.4 years, range: 14.2-62.3 years) with
      triple labrum tears underwent arthroscopic repair using the 1.4 mm JuggerKnot
      Soft Anchor (mean number of anchors 11.5, range: 9-19 anchors). Five patients had
      prior surgeries performed on their operative shoulder. Patients were followed for
      a mean of 2.0 years (range: 1.6-3.0 years). Constant-Murley shoulder score (CS)
      and Flexilevel scale of shoulder function (FLEX-SF) scores were measured, with
      preoperative and final postoperative mean scores compared with a paired Student's
      t-test (P < 0.05). Magnetic resonance imaging (MRI) was also performed at final
      postoperative. RESULTS: Overall total CS and FLEX-SF scores increased from 52.9
      +/- 20.4 to 84.3 +/- 10.7 (P < 0.0001) and from 29.3 +/- 4.7 to 42.0 +/- 7.3 (P <
      0.0001), respectively. When divided into two groups by whether or not
      glenohumeral arthrosis was present at the time of surgery (n = 9 each group),
      significant improvements in CS and FLEX-SF were obtained for both groups (P <
      0.0015). There were no intraoperative complications. All patients, including
      contact athletes, returned to their preinjury level of sports activity and were
      satisfied. MRI evaluation revealed no instances of subchondral cyst formation or
      tunnel expansion. Anchor tracts appeared to heal with fibrous tissue, complete
      bony healing, or combined fibro-osseous healing. CONCLUSION: Our results are
      encouraging, demonstrating a consistent healing of the anchor tunnels through
      arthroscopic treatment of complex labrum lesions with a completely suture-based
      implant. It further demonstrates a meaningful improvement in patient outcomes, a
      predictable return to activity, and a high rate of patient satisfaction. LEVEL OF
      EVIDENCE: Level IV case series.

PMID- 26288538
TI  - Sorting swimmers shoulders: An observational study on swimmers that presented to
      a shoulder surgeon.
AB  - CONTEXT: It is common for swimmers to suffer shoulder injuries resulting in a
      wealth of research focusing on the causes and types of injury. However, there is
      a lack of evidence regarding current management for shoulder injuries in
      swimmers. AIMS: To investigate the diagnosis, subsequent management, and the
      return to swimming outcomes for swimmers presenting to an orthopedic practice.
      SETTINGS AND DESIGN: Retrospective cohort study of competitive swimmers
      presenting to an orthopedic practice. MATERIALS AND METHODS: The diagnosis,
      subsequent management, and the return to swimming outcomes were analyzed for 14
      swimmers whose injuries were managed by a shoulder surgeon. STATISTICAL ANALYSIS
      USED: Descriptive analysis. RESULTS: No significant association was identified
      between swimming stroke and type of injury. The majority of swimmers had good
      scapula rhythm, with no visible dyskinesis, including those with impingement.
      Swimmers with impingement did not require arthroscopy, and with nonoperative
      management had a mean time to return to swimming of 1.6 months. All labral tears
      required arthroscopic labral repair, with these swimmers having a mean time of
      2.9 months postsurgery to return to swimming. CONCLUSION: The study demonstrated
      that an accurate diagnosis, and appropriate choice of nonoperative and surgical
      treatments lead to reassuring outcomes for swimmers suffering from shoulder
      injuries.

PMID- 26288539
TI  - One step arthroscopically assisted Latarjet and posterior bone-block, for
      recurrent posterior instability and anterior traumatic dislocation.
AB  - This case presents the challenges of the surgical management for a patient with a
      history of recurrent posterior shoulder instability and subsequently traumatic
      anterior dislocation. The patient was already on the waiting list for an
      arthroscopic posterior stabilization with anchors, when a car accident caused an
      additional anterior shoulder dislocation. This traumatic anterior dislocation
      created a bone loss with a glenoid fracture and aggravated the preexisting
      posterior instability. In order to address both problems, we decided to perform
      an arthroscopically assisted Latarjet procedure for anterior instability and to
      stabilize with a bone graft for posterior instability. To our best knowledge,
      this type of surgical procedure has so far never been reported in the literature.
      The purpose of this report is to present the surgical technique and to outline
      the decision making process. 

PMID- 26288540
TI  - Warm irrigation fluid does not raise the subacromial temperature to harmful
      levels while using radiofrequency device.

PMID- 26288541
TI  - A rare case of spontaneous acute bacterial arthritis of the glenohumeral joint
      attributed to Streptococcus dysgalactiae subsp. equisimilis.

PMID- 26288542
TI  - Spinal fixation as treatment of ossified posterior longitudinal ligament.

PMID- 26288543
TI  - Is inclusion of the occipital bone necessary/counter-effective for
      craniovertebral junction stabilization?

PMID- 26288545
TI  - Morphometric analysis of hypoglossal canal of the occipital bone in Iranian dry
      skulls.
AB  - BACKGROUND: The hypoglossal canal (HC) is in basal part of cranium that transmits
      the nerve that supplies the motor innervations to the muscles of tongue. Study on
      morphometry of (HC) and its variations has been a considerable interest field to
      neurosurgeons and research workers especially because of their racial and
      regional. MATERIAL AND METHODS: In this retrospective study, 26 adult dry human
      crania of no sex known were studied for (HC) and its variants. Thirty five skulls
      were observed for any damage of post cranial fossa and those in good condition
      (26 skulls)were selected. Sliding Vernier caliper was used for morphometric
      analysis. RESULTS: There were significant difference between distances of: a-(HC)
      till anterior tip of condyles (right and left), b-(HC) till posterior tip of
      condyles (right and left), c-(HC)till lower border of occipital condyles (right
      and left), d-(HC) till external border of foramen jugular (right and left), e
      (HC) till opisthion(right and left), f-(HC) till carotid canal (right and left),
      g-(HC) till jugular tubercle (right and left). There wasn't significant
      difference in other parameters. CONCLUSION: Detailed morphometric analysis of
      (HC) will help in planning of surgical intervention of skull base in safer and
      easier ways.

PMID- 26288544
TI  - Pain management following spinal surgeries: An appraisal of the available
      options.
AB  - Spinal procedures are generally associated with intense pain in the postoperative
      period, especially for the initial few days. Adequate pain management in this
      period has been seen to correlate well with improved functional outcome, early
      ambulation, early discharge, and preventing the development of chronic pain. A
      diverse array of pharmacological options exists for the effective amelioration of
      post spinal surgery pain. Each of these drugs possesses inherent advantages and
      disadvantages which restricts their universal applicability. Therefore,
      combination therapy or multimodal analgesia for proper control of pain appears as
      the best approach in this regard. The current manuscript discussed the
      pathophysiology of postsurgical pain including its nature, the various tools for
      assessment, and the various pharmacological agents (both conventional and
      upcoming) available at our disposal to respond to post spinal surgery pain. 

PMID- 26288546
TI  - Surgical management of metastatic lesions at the cervicothoracic junction.
AB  - PURPOSE: The cervicothoracic junction (CTJ) represents a transition from the
      semirigid thoracic spine to the mobile subaxial cervical spine. Pathologic
      lesions are prone to kyphotic deformity. The aim of this study was to review our
      experience with surgical stabilization of metastatic lesions affecting the CTJ
      (C7-T2). MATERIALS AND METHODS: We reviewed all surgical stabilizations of
      metastatic spine lesions over the preceding 4 years in our institution. A total
      of 14 patients with CTJ lesions were identified. Case notes and radiology were
      reviewed to determine the presentation, outcomes, and specific complications.
      RESULTS: The mean survival was 405 days (standard deviation [s.d.] 352). 8/14
      died at a mean time from surgery of 193 days (s.d. 306). Most cases were a result
      of either lung or breast primary tumors. Half were stabilized with an anterior
      only approach and two had staged anterior-posterior. There were no cases of
      neurologic deterioration in this cohort as a result of surgery. There were two
      cases of deep surgical site infection and two documented cases of pulmonary
      embolus. There were no reported construct failures over the follow-up period.
      CONCLUSION: Patients with cervicothoracic metastatic lesions can be treated with
      either anterior or posterior approaches or a combination after considering each
      individual's potential instability and disease burden.

PMID- 26288547
TI  - Prediction of the efficacy of surgical intervention in patients with cervical
      myelopathy by using diffusion tensor 3T-magnetic resonance imaging parameters.
AB  - BACKGROUND: The clinical significance of diffusion tensor (DT) magnetic resonance
      imaging (MRI) parameters was analyzed to predict postoperative functional
      recovery in patients with cervical myelopathy. MATERIALS AND METHODS: Sixteen
      patients with cervical myelopathy caused by cervical spondylosis, disk herniation
      or ossification of the posterior longitudinal ligament who underwent surgical
      intervention in our institute were enrolled in this retrospective study. There
      were 7 men and 9 women, with a mean age of 62.8 years. Clinical assessment was
      done before surgery and at least 3 months after surgery. All patients underwent
      whole-body 3.0-Tesla MRI before surgery. DT images (DTIs) were obtained using a
      single-shot fast spin-echo-based sequence. Mean values of mean diffusivity (MD)
      and fractional anisotropy (FA) at 6 disk levels of the cervical spine were
      measured using manual setting of regions of interest. The MD and FA values at the
      most compressed part were analyzed. Absolute MD and FA values at the most
      compressed spinal level in patients were transformed into the normalized values
      with a z-score analysis. RESULTS: MD-z may decrease with the severity of cervical
      myelopathy. Receiver operating characteristic analysis of MD-z and FA-z suggested
      that both MD-z and FA-z have clinical validity for predicting the efficacy of
      surgical intervention, but MD-z was considered to be the most appropriate value
      to predict the efficacy of surgery. CONCLUSIONS: DTIs may be a promising modality
      to predict functional recovery after surgery. MD changes may reflect spinal cord
      condition and its reversibility.

PMID- 26288548
TI  - Scoliosis curve analysis with Milwaukee orthosis based on Open SIMM modeling.
AB  - BACKGROUND: Scoliosis is a three-dimensional spinal deformity characterized by
      lateral curvature and rotational deformity of the spine. Various methods have
      been used to investigate the performance of the subjects during walking with an
      orthosis, but nobody study the biomechanics of orthotic use by understanding the
      length of the muscles and the force produced by them. Therefore, the aim of this
      research is to test the effect of the orthosis on the muscular force, tendon
      length during walking with and without orthosis. MATERIALS AND METHODS: A 12-year
      old scoliosis subject was recruited in this study. The forces produced by trunk
      musculature, joint reaction force, length of trunk musculature were some
      parameters selected in this study. Open SIMM and Visual 3D software were used to
      model the subject. RESULTS: The results of this research showed that the length
      of erector spine muscles increased follow the use of orthosis. Moreover, the
      force produced by trunk muscles differed during walking with and without orthosis
      and also between right and left sides. DISCUSSION: It seems that Open SIMM
      software can be used to predict the length of muscles, active-passive forces
      produced by muscles in scoliotic subjects. Therefore, it is recommended this
      research be done on more number of subjects.

PMID- 26288549
TI  - Locally aggressive aneurysmal bone cyst of C4 vertebra treated by total en bloc
      excision and anterior plus posterior cervical instrumentation.
AB  - We are presenting a case of cervical (C4) aneurysmal bone cyst in a 13-year-old
      girl, came to the outpatient department with neck pain and stiffness since 6
      months and normal neurology. We did an en bloc excision of locally aggressive
      tumor through anterior plus posterior approach and stabilization by lateral mass
      screw fixation and anterior cervical instrumentation. Involvement of several
      adjacent cervical vertebrae by an aneurysmal bone cyst is rare, and conventional
      treatment with curettage and bone grafting is most likely to carry a high rate of
      recurrence and spinal instability. We recommend complete excision of the tumor
      and instrumentation in a single stage to avoid instability. 

PMID- 26288550
TI  - Multicentric intradural extramedullary ependymoma: Report of a rare case.
AB  - Spinal ependymoma commonly presents as an intramedullary tumor. We present a rare
      case of multicentric intradural extramedullary spinal ependymoma. A 59 years old
      female presented to us with spastic quadriparesis for 10 months. Magnetic
      resonance imaging of the spinal cord showed discretely located enhancing tumor
      masses from at C1-C2, C6-C7, and D4 to L3 level. Subtotal resection of the
      symptomatic tumor at C6-C7 and D7-D9 was done. The patient underwent radiotherapy
      with 50.4 Gy. At follow-up of 11 months, patient is doing well. The relevant
      literature is reviewed. 

PMID- 26288551
TI  - "Only fixation:" Simple act, but mammoth stride toward great aspiration in
      managing cervical spondylotic myelopathy.

PMID- 26288552
TI  - Molecular identification of isolated fungi, microbial and heavy metal
      contamination of canned meat products sold in Riyadh, Saudi Arabia.
AB  - Several studies have shown that canned meat products may be contaminated with
      fungal elements, bacteria and even heavy metals which may occur during the
      transportation, storage and handling processes. We conducted this study to
      determine the fungal, microbial and heavy metal contents of canned meats in Saudi
      Arabia. Of the 13 canned meat samples studied, Aspergillus and Penicillium were
      found in more than 70% of the total samples. Sequences of Penicillium species
      isolated from meat samples generated a phylogenetic tree which shows that the
      studied isolates were clustered in four groups. No bacterial contamination was
      noted in all of the samples. Nine of the 13 samples had iron concentrations above
      the permissible limit. All samples had zinc and copper levels below the maximum
      permissible limit. Four samples had cadmium levels above the maximum permissible
      level. All samples had levels of lead above the maximum permissible levels. These
      results indicate that fungal elements and higher levels of heavy metals such as
      lead and cadmium can be found in canned meat products. This may pose as a real
      danger to consumers, since canned meat products are readily accessible and
      convenient in Saudi Arabia. 

PMID- 26288553
TI  - Antimicrobial activities of Saudi honey against Pseudomonas aeruginosa.
AB  - Five types of imported and local honey were screened for both their
      bacteriocidal/bacteriostatic activities against both Imipenem resistant and
      sensitive Pseudomonas aeruginosa in both Brain Heart infusion broth and Mueller
      Hinton agar. The results indicated that the effect was concentration and type of
      honey dependant. All types of honey tested exerted a full inhibition of bacterial
      growth at the highest concentration tested of 50% at 24 h of contact. The
      inhibitory effect of honey on bacterial growth was clear with concentrations of
      20% and 10% and this effect was most evident in the case of Manuka honey as
      compared to Nigella sativa honey and Seder honey. Manuka honey UMF +20 showed a
      bacteriocidal activity on both Imipenem resistant and sensitive P. aeruginosa,
      while Seder honey and N. sativa honey exerted only a bacteriostatic effect.
      Manuka honey UMF +10 showed most effect on antimicrobial resistance. Manuka honey
      UMF +10 had an effect on modulation of Imipenem resistant P. aeruginosa.
      CONCLUSION: The results indicated that various types of honey affected the test
      organisms differently. Modulation of antimicrobial resistance was seen in the
      case Manuka honey UMF +10.

PMID- 26288554
TI  - Research on soybean protein wastewater treatment by the integrated two-phase
      anaerobic reactor.
AB  - The start-up tests of treating soybean protein wastewater by the integrated two
      phase anaerobic reactor were studied. The results showed that the soybean protein
      wastewater could be successfully processed around 30 days when running under the
      situation of dosing seed sludge with the influent of approximately 2000 mg/L and
      an HRT of 40 h. When the start-up was finished, the removal rate of COD by the
      reactor was about 80%. In the zone I, biogas mainly revealed carbon dioxide (CO2)
      and hydrogen (H2). Methane was the main component in the zone 2 which ranged from
      53% to 59% with an average of 55%. The methane content in biogas increased from
      the zone I to II. It indicated that the methane-producing capacity of the
      anaerobic sludge increased. It was found that the uniquely designed two-phase
      integrated anaerobic reactor played a key role in treating soybean protein
      wastewater. The acidogenic fermentation bacteria dominated in the zone I, while
      methanogen became dominant in the zone II. It realized the relatively effective
      separation of hydrolysis acidification and methanogenesis process in the reactor,
      which was benefit to promote a more reasonable space distribution of the
      microbial communities in the reactor. There were some differences between the
      activities of the sludge in the two reaction zones of the integrated two-phase
      anaerobic reactor. The activity of protease was higher in the reaction zone I.
      And the coenzyme F420 in the reaction zone II was twice than that in the reaction
      zone I, which indicated that the activity of the methanogens was stronger in the
      reaction zone II. 

PMID- 26288555
TI  - Anti-influenza (H1N1) potential of leaf and stem bark extracts of selected
      medicinal plants of South India.
AB  - Variations in antioxidant and anti-viral activities (against Influenza AP/R/8
      (H1N1) virus) between the leaves and stem bark of selected medicinal plants were
      studied. Malin Darby canine kidney (MDCK) cells were used for the viral infection
      and the antiviral activity of the extracts was studied using sulphorhodamine B
      (SRB) assay. The stem bark of the plants including Strychnos minor, Diotacanthus
      albiflorus, Strychnos nux-vomica and Chloroxylon swietenia showed higher
      flavonoid contents as well as 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic
      acid) (ABTS) scavenging activity when compared with their leaves. In case of 1,1
      diphenyl-2-picrylhydrazyl (DPPH) activity, the stem bark of S. nux-vomica and
      leaf extract of C. swietenia showed the highest activity. Based on the IC50
      values, the stem bark extracts of Cayratia pedata (20.5 MUg/mL) and S. minor
      (22.4 MUg/mL) showed high antiviral activity. In the mean-time S. nux-vomica, C.
      swietenia and C. swietenia bark extracts showed cytotoxicity to the MDCK cells.
      When comparing the stem bark and leaves the content of gallic acid, ferulic acid,
      o-coumaric acid, total flavonoids (TFC) and total phenols (TPC) was higher in
      stem bark and hence their anti-viral activity was high. Further study based on
      the metabolites against H1N1 can reveal the potential of therapeutic compounds
      against the viral disease. 

PMID- 26288556
TI  - Haematological and biochemical parameters and tissue accumulations of cadmium in
      Oreochromis niloticus exposed to various concentrations of cadmium chloride.
AB  - Oreochromis niloticus, weighing 36.45 +/- 1.12 g were exposed to 10%, 20% and 30%
      of the LC50 of CdCl2 which represents treatments (T1)1.68, (T2)3.36 and (T3)5.03
      mg/l, respectively, for a period of 10, 20 and 30 days. It was found that,
      compared to a control group reading of 0.19 +/- 0.03 MUg/g dry weight,
      accumulation of Cd in the gills was significantly (p < 0.05) increased in samples
      ranging between 7.64 +/- 0.86 and 61.73 +/- 0.82 MUg/g dry weight from T1 at 10
      days to T3 at 30 days. The accumulation of Cd in the liver, meanwhile, was also
      observed to significantly increase (p < 0.05) with increasing time and
      concentrations with results ranging between 3.21 +/- 0.12 and 181.61 +/- 1.32
      compared to the control group results of 0.29 +/- 0.04 MUg/g dry weight. Although
      muscles exhibited lower levels of accumulation than the gills and liver they
      still showed the same pattern of increase compared to the control group, with a
      significant difference ranging between 0.32 +/- 0.02 and 2.16 +/- 0.08 compared
      to the control group results of 0.03 +/- 0.001 MUg/g dry weight. Also,
      haematological parameters such as red blood cells (RBCs), haemoglobin (Hb) and
      haematocrit (Hct) were reduced in fish exposed to Cd at all periods, with
      significant differences (p < 0.05). Plasma glucose concentration showed a
      significant increase. Total protein levels of fish showed a significant reduction
      (p > 0.05) for all exposed treatments. Also, the total lipid level increased
      significantly as fish were exposed to increasing cadmium concentrations, compared
      to control fish. Finally, the activities of aspartate aminotransferase (AST IU/l)
      and alanine aminotransferase (ALT IU/l) showed a significant increase (p < 0.05)
      with increasing time and concentrations. 

PMID- 26288557
TI  - Protective effect of berberine chloride on Plasmodium chabaudi-induced hepatic
      tissue injury in mice.
AB  - The present study aimed to investigate the protective role of berberine (BER)
      against Plasmodium chabaudi-induced infection in mice. Animals were divided into
      three groups. Group I served as a vehicle control. Group II and group III were
      infected with 1000 P. chabaudi infected erythrocytes. Group III was gavaged with
      100 MUl of 10 mg/kg berberine chloride for 10 days. All mice were sacrificed at
      day 10 post-infection. The percentage of parasitemia was significantly reduced
      more than 30%, after treatment of mice with BER. Infection caused marked hepatic
      injuries as indicated by histopathological alterations as evidenced by the
      presence of hepatic lobular inflammatory cellular infiltrations, dilated
      sinusoids, vacuolated hepatocytes, increased number of Kupffer cells and the
      malaria pigment, hemozoin. These changes in livers led to the increased
      histological score. Also, infection induced a significant increase in liver
      alanine aminotransferase and aspartate aminotransferase and a significant
      increase in the total leucocytic count. Moreover, mice became anemic as proved by
      the significant decrease in erythrocyte number and haemoglobin content. BER
      showed a significant protective potential by improving the above mentioned
      parameters. Based on these results, it is concluded that berberine could offer
      protection against hepatic tissue damage. 

PMID- 26288558
TI  - Hematological and biochemical investigations on the effect of vitamin E and C on
      Oreochromis niloticus exposed to zinc oxide nanoparticles.
AB  - This study was carried out to determine the LC50 of zinc oxide nanoparticles
      (ZnONPs) on Oreochromis niloticus and to investigate the effect of vitamin E and
      C on hematological and biochemical alterations induced by two sublethal
      concentrations (1 and 2 mg/L) of ZnONPs. One hundred and eighty fish were used
      for studying the lethal concentrations of ZnONPs. For sublethal study two hundred
      and twenty-five males of O. niloticus were equally divided into five groups,
      control, the second and the third were treated with 1 and 2 mg/L ZnONPs
      respectively. The fourth and fifth were exposed to the same concentrations of
      ZnONPs plus vitamins E and C. The results revealed that the 96 h LC50 of ZnONPs
      was 3.1 +/- 0.4 mg/L. The sublethal study revealed the presence of normocytic
      normochromic anemia in groups (2, 3 and 5) along the experiment period. The 4th
      group showed normocytic normochromic anemia at the 7th day and microcytic
      hypochromic anemia at the 15th day. Leukocytosis, heterophilia, lymphopenia and
      monocytopenia were recorded at the 7th day in all treated groups compared with
      the normal control. At the 15th day heteropenia, lymphopenia and monocytopenia
      were reported in all treated groups. A significant increase in the serum levels
      of alkaline phosphatase, aminotransferases, urea, creatinine and erythrocytic
      nuclear and morphological abnormalities along the experimental periods in all
      treated groups compared with the normal control. Serum total protein and albumin
      levels were significantly decreased at the same period in the same groups.
      Addition of vitamin E and C to the diet (groups 4 and 5) significantly improved
      all measured parameters compared with groups (2 and 3) which treated with ZnONPs
      only. 

PMID- 26288560
TI  - Interaction between Meloidogyne incognita and Rhizoctonia solani on green beans.
AB  - The interaction between Meloidogyne incognita (race 2) and Rhizoctonia solani (AG
      4) in a root rot disease complex of green beans (Phaseolus vulgaris) was examined
      in a greenhouse pot experiment. Three week-old seedlings (cv. Contender) were
      inoculated with the nematode and/or the fungus in different combinations and
      sequences. Two months after last nematode inoculation, the test was terminated
      and data were recorded. The synchronized inoculation by both pathogens (N + F)
      increased the index of Rhizoctonia root rot and the number of root galls; and
      suppressed plant growth, compared to controls. However, the severity of root rot
      and suppression of plant growth were greater and more evident when inoculation by
      the nematode preceded the fungus (N -> F) by two weeks. Nematode reproduction
      (eggs/g root) was adversely affected by the presence of the fungus except by the
      synchronized inoculation. When inoculation by nematode preceded the fungus, plant
      growth was severely suppressed and roots were highly damaged and rotted leading
      to a decrease of root galls and eggs. 

PMID- 26288559
TI  - Biotin amelioration of nephrotoxicity in streptozotocin-induced diabetic mice.
AB  - The current study was carried out to investigate the protective role of biotin in
      kidney injury and oxidative stress in diabetic mice type 1. Male Swiss albino
      mice were randomly divided into 3 groups. Control group received saline. Diabetes
      type 1 was induced in second and third groups by intraperitoneal injection of
      streptozotocin as a single dose (150 mg/kg). Second group remained as the
      untreated diabetic group and the third group received 15 mg/kg daily oral dose of
      biotin for 12 successive days. Biochemical results showed significant elevation
      in blood glucose and urea levels in both diabetic groups. Also, there is an
      increase in glomerular areas and decrease in glomerular cellularity in both
      diabetic groups. Histopathological results showed severe alterations in the
      untreated diabetic group represented by distorted glomeruli, inflammatory cells,
      and giant macrophages. In addition, there was an intense immune-reaction response
      toward acrolein indicator of oxidative damage. Upon biotin administration of
      diabetic mice, the above mentioned histopathological changes were reduced and
      also acroline reaction of oxidative damage was diminished. Our findings prove
      that biotin has a protective role against streptozotocin-induced oxidative damage
      in kidneys of laboratory mice. 

PMID- 26288561
TI  - Samsum ant, Brachyponera sennaarensis (Formicidae: Ponerinae): Distribution and
      abundance in Saudi Arabia.
AB  - Invasive species are capable of causing considerable damage to natural
      ecosystems, agriculture and economies throughout the World. Samsum ant,
      Brachyponera (Pachycondyla) sennaarensis has been a reason for medical
      implication and social nuisance through its poisonous and severely painful sting
      causing anaphylactic shock in many cases. We surveyed for the presence of the
      samsum ant in various provinces of Saudi Arabia. B. sennaarensis was the abundant
      Ponerinae species in human settlements. In the Eastern provinces, however, few
      samples were collected, and none were found in the Northern and Western
      provinces. Infestations of B. sennaarensis were particularly severe in the spring
      and summer seasons, when the ants make nests in moist areas and in cracks in
      cemented structures, whereas the extent of infestation reduced in winter seasons.

PMID- 26288562
TI  - Evaluating agro-industrial by-products as dietary roughage source on growth
      performance of fattening steers.
AB  - Silages from pineapple peel, sweet corn husk and cob mixed with bagasse and
      vinasse were evaluated to determine their chemical composition and fermentation
      characteristics as well as feeding performance in fattening steers. The
      experiment, which lasted 90 days, involved 48 fattening steers (264 +/- 37.4 kg
      BW) randomly allocated to three diets. Treatments included: a control diet
      containing rice straw and molasses (T1); diet containing bagasse-vinasse mixture
      including sweet corn husk and cob silage (BS; T2); and diet containing bagasse
      vinasse mixture including pineapple peel silage (BP; T3). All treatments included
      a commercial concentrate feed (13% CP) and ad libitum rice straw throughout the
      experiment. Results from chemical analysis showed that dry matter (DM) of BS was
      higher than BP (P < 0.05), whereas the protein content of BS and BP was similar
      (P > 0.05). For fermentation characteristics, pH in BP was lower than BS (P <
      0.05); in addition, acetic and butyric acids in BS were higher than BP (P <
      0.05). Findings from growth trial showed that total DM intake in steers fed T1
      was higher compared to the other dietary treatments (P < 0.05), whereas the
      average BW gain was found to be grater in T3 steers (P < 0.05). As result from
      our findings, bagasse-vinasse mixture with pineapple peel silage appeared to be a
      viable feed ingredient in fattening steer diet and moreover it could become an
      economically feasible agro-industrial by-product for farmers. 

PMID- 26288563
TI  - Salt tolerant Methylobacterium mesophilicum showed viable colonization abilities
      in the plant rhizosphere.
AB  - The source of infection has always been considered as an important factor in
      epidemiology and mostly linked to environmental source such as surface water,
      soil, plants and also animals. The activity of the opportunistic pathogens
      associated with plant root, their adaptation and survival under hostile
      environmental condition is poorly understood. In this study the salt tolerance
      ability of Methylobacterium mesophilicum and its colonization in the root and
      shoot of plants under severe drought and salt stress conditions were
      investigated. The colonization of plant by M. mesophilicum was investigated in a
      gnotobiotic sand system, and their survival in pots with saline soil. Bacterial
      strain was found to colonize rhizosphere of cucumber, tomato and paprika grown
      under normal and salt stress condition and reached up to 6.4 * 10(4) and 2.6 *
      10(4) CFU/g root. The strain was resistant to Gentamicin, Ampicillin, Amoxicillin
      plus Clavulanic acid, Cefotaxime, neomycin, penicillin and was also tolerant to
      salinity stress (up to 6% NaCl). These abilities play important roles in enabling
      persistent colonization of the plant surface by M. mesophilicum strains. In
      conclusion, this study provides background information on the behaviour of
      opportunistic pathogen M. mesophilicum on plants and their survival in harsh
      environmental conditions. 

PMID- 26288564
TI  - Assessment of ISSR based molecular genetic diversity of Hassawi rice in Saudi
      Arabia.
AB  - Inter simple sequence repeat (ISSR) analysis, using 14 primers was performed to
      estimate genetic diversity among 27 landraces of Hassawi rice growing in Al-Ahsa
      region of Saudi Arabia and deposited at King Abdulaziz City for Science and
      Technology with KACST IDs. The average polymorphism produced by 11 selected
      primers was more than 75%. The analysis of ISSR polymorphism divided the examined
      rice landraces into two groups; In one group (A), one accession (KACST 191) was
      clearly delimited as a distant landrace from other 12 landraces grouped in two
      clusters; cluster I of seven landraces of close geographic distributions; four of
      them grow at close geographic locations (KACST IDs 32, 183, 184, 185, 186, 187
      and 188) and cluster II is comprised of five landraces KACST IDs (190, 308, 352,
      353 and 355). In group B, the landraces were more closely related to each other
      as compared to the landraces of group A. In this group a small cluster of two
      landraces (KACST 305 & KACST 333) was clearly distant from a large group of three
      clusters comprised of landraces having KACST IDs 189 & 192, landraces 302, 306,
      307, 308 & 310 and landraces with KACST IDs 334, 351, 354, 356 & 357
      respectively. These results indicate that ISSR fingerprints are efficient in the
      identification and resolution of genetic diversity between the landraces of the
      Hassawi rice and will be an efficient method in the authentication of the rice
      germplasm in the gene bank of Saudi Arabia. 

PMID- 26288565
TI  - Mycelium of fungi isolated from mouldy foods inhibits Staphylococcus aureus
      including MRSA - A rationale for the re-introduction of mycotherapy?
AB  - Fungal mycelium capable of producing antibacterial agents was isolated from
      samples of apple, beetroot, lemon and orange; the mycelium of all isolates
      produced penicillin, while the apple and beetroot samples also produced the
      antibacterial mycotoxin patulin. The known penicillin-producing fungi were shown
      to produce penicillin, but not patulin. The mycelial discs of all of fruit and
      vegetable isolates, as well as the two known penicillin producing fungi,
      inhibited Staphylococcus aureus, and mycelium of all isolates inhibited MRSA, in
      contrast, only one of the two known penicillin-producers did so. The results are
      discussed in relation to the possibility of using the mycelium of Penicillium
      species in mycotherapy. 

PMID- 26288566
TI  - Dermatophyte and non dermatophyte fungi in Riyadh City, Saudi Arabia.
AB  - BACKGROUND: Dermatophytes are a scientific label for a group of three genera
      (Microsporum, Epidermophyton and Trichophyton) of fungus that causes skin disease
      in animals and humans. Conventional methods for identification of these fungi are
      rapid and simple but are not accurate comparing to molecular methods. OBJECTIVE:
      This study aimed to isolate human pathogenic dermatophytes which cause
      dermatophytosis in Riyadh City, Saudi Arabia and to identify these fungi by using
      conventional and molecular methods. METHODS: The study was conducted in Medical
      Complex, Riyadh and King Saud University. Samples of infected skin, hairs and
      nails were collected from 112 patients. Diagnosis of skin infections, direct
      microscopic test, isolation and identification of dermatophytes by conventional
      and molecular methods were carried out. RESULTS: The results indicated that the
      tinea capitis infection had the highest prevalence among the patients (22.3%)
      while Tinea barbae had the lowest. In this study the identified dermatophyte
      isolates belong to nine species as Trichophyton violaceum, Trichophyton
      verrucosum, Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton
      schoenleinii, Trichophyton concentricum, Microsporum canis, Microsporum audouinii
      and Epidermophyton floccosum which cause skin infections were isolated during
      this study. Non dermatophyte isolates included 5 isolates from Aspergillus spp. 4
      isolates from Acremonium potronii and 15 isolates from Candida spp. M. canis were
      the most common species (25% of isolated dermatophytes). Out of the 52
      dermatophyte isolates identified by conventional methods, there were 45 isolates
      identified by the molecular method. CONCLUSIONS: The results concluded that
      approximately M. canis caused a quarter of dermatophyte cases, tinea capitis
      infection was prevalent and the molecular method was more accurate than
      conventional methods.

PMID- 26288567
TI  - Identifying new targets in leukemogenesis using computational approaches.
AB  - There is a need to identify novel targets in Acute Lymphoblastic Leukemia (ALL),
      a hematopoietic cancer affecting children, to improve our understanding of
      disease biology and that can be used for developing new therapeutics. Hence, the
      aim of our study was to find new genes as targets using in silico studies; for
      this we retrieved the top 10% overexpressed genes from Oncomine public domain
      microarray expression database; 530 overexpressed genes were short-listed from
      Oncomine database. Then, using prioritization tools such as ENDEAVOUR, DIR and
      TOPPGene online tools, we found fifty-four genes common to the three
      prioritization tools which formed our candidate leukemogenic genes for this
      study. As per the protocol we selected thirty training genes from PubMed. The
      prioritized and training genes were then used to construct STRING functional
      association network, which was further analyzed using cytoHubba hub analysis tool
      to investigate new genes which could form drug targets in leukemia. Analysis of
      the STRING protein network built from these prioritized and training genes led to
      identification of two hub genes, SMAD2 and CDK9, which were not implicated in
      leukemogenesis earlier. Filtering out from several hundred genes in the network
      we also found MEN1, HDAC1 and LCK genes, which re-emphasized the important role
      of these genes in leukemogenesis. This is the first report on these five
      additional signature genes in leukemogenesis. We propose these as new targets for
      developing novel therapeutics and also as biomarkers in leukemogenesis, which
      could be important for prognosis and diagnosis. 

PMID- 26288568
TI  - Antioxidant activity and mineral composition of three Mediterranean common
      seaweeds from Abu-Qir Bay, Egypt.
AB  - Antioxidant activity and mineral composition were evaluated seasonally from
      spring to autumn 2010 in the three common seaweeds Ulva lactuca Linnaeus
      (Chlorophyta), Jania rubens (Linnaeus) J.V. Lamouroux and Pterocladia capillacea
      (S.G. Gmelin) Bornet (Rhodophyta). The antioxidant activity was measured with
      beta-carotene, total phenol content and DPPH (2,2-diphenyl-1-picrylhydrazyl).
      Seaweeds were collected from the rocky site near Boughaz El-Maadya Abu-Qir Bay of
      Alexandria, Egypt. The results showed maximum increase of beta-carotene in P.
      capillacea during summer. A significant increase in total phenolic content at P ?
      0.05 was found in the red alga (J. rubens) during summer. Also, U. lactuca showed
      the maximum antioxidant scavenging activity especially during summer. Minerals in
      all investigated samples were higher than those in conventional edible
      vegetables. Na/K ratio ranged between 0.78 and 2.4 mg/100 g, which is a favorable
      value. All trace metals exceeded the recommended doses by Reference Nutrient
      Intake (RNI). During summer season, it was found that Cu = 2.02 +/- 0.13 and Cr =
      0.46 +/- 0.14 mg/100 g in U. lactuca and Fe had a suitable concentration (18.37
      +/- 0.5 mg/100 g) in P. capillacea. The studied species were rich in carotenoids,
      phenolic compounds, DPPH free radicals and minerals, therefore, they can be used
      as potential source of health food in human diets and may be of use to food
      industry. 

PMID- 26288569
TI  - A new species of Leptadenia (Apocynaceae) and two other new records from
      southwestern Saudi Arabia.
AB  - Leptadenia jazanica Y. Masrahi from the province of Jazan, southwestern Saudi
      Arabia is described as a new species and illustrated. The species differs from
      the other known nearest species of the genus, Leptadenia pyrotechnica, by
      decumbent to scrambling habit of stems and persistent leaves. In the same
      province also two new records belonging to the genera Canavalia (Fabaceae) and
      Craterostigma (Scrophulariaceae) were collected; they were identified as
      Canavalia virosa (Roxb.) Wight & Arn. and Craterostigma plantagineum Hochst. 

PMID- 26288570
TI  - Green synthesis and characterization of Carica papaya leaf extract coated silver
      nanoparticles through X-ray diffraction, electron microscopy and evaluation of
      bactericidal properties.
AB  - The evolution of nanotechnology and the production of nanomedicine from various
      sources had proven to be of intense value in the field of biomedicine. The
      smaller size of nanoparticles is gaining importance in research for the treatment
      of various diseases. Moreover the production of nanoparticles is eco-friendly and
      cost effective. In the present study silver nanoparticles were synthesized from
      Carica papaya leaf extract (CPL) and characterized for their size and shape using
      scanning electron microscopy and transmission electron microscopy, respectively.
      Fourier transform infrared spectroscopy (FTIR), Energy dispersive X-ray
      spectroscopy (EDS/EDX) and X-ray diffraction spectroscopy (XRD) were conducted to
      determine the concentration of metal ions, the shape of molecules. The
      bactericidal activity was evaluated using Luria Bertani broth cultures and the
      minimum inhibition concentration (MIC) and minimum bactericidal concentration
      (MBC) were estimated using turbidimetry. The data analysis showed size of 50-250
      nm spherical shaped nanoparticles. The turbidimetry analysis showed MIC and MBC
      was >25 MUg/mL against both Gram positive and Gram negative bacteria in Luria
      Bertani broth cultures. In summary the synthesized silver nanoparticles from CPL
      showed acceptable size and shape of nanoparticles and effective bactericidal
      activity. 

PMID- 26288571
TI  - Evaluation of antioxidant and neuroprotective effect of Hippophae rhamnoides (L.)
      on oxidative stress induced cytotoxicity in human neural cell line IMR32.
AB  - AIM AND OBJECTIVE: Hippophae rhamnoides is an edible, nutrient rich plant found
      in the northern regions of India. It belongs to the family Elaeagnaceae and is
      well known for its traditional pharmacological activities. The present study was
      aimed to investigate the antioxidant and neuroprotective activities of H.
      rhamnoides. METHODOLOGY: The hydroalcoholic extract of H. rhamnoides was
      evaluated for free radical scavenging activity using DPPH, hydroxyl radical
      scavenging and ferric thiocyanate assays. In vitro neuroprotective activity was
      assessed on human neuroblastoma cell line-IMR32 against hydrogen peroxide (H2O2)
      induced cytotoxicity. The neuroprotective effect was determined by measuring the
      cell viability through tetrazolium dye MTT (3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide) reducing assay and propidium iodide (PI) staining.
      Also the intracellular reactive oxygen species (ROS) activity was assessed using
      dichloro-dihydro-fluorescein diacetate (DCFDA) assay by flowcytometer. RESULTS:
      The results of the study demonstrated that H. rhamnoides extract possesses
      potential free radical scavenging activity. The IC50 value for DPPH and OH
      radical scavenging assay was 70.92 MUg/ml and 0.463 mg/ml, also the extract was
      also found to have considerable level of lipid peroxidation activity. The
      neuroprotective effect of H. rhamnoides was confirmed by its cell viability
      enhancing capacity against hydrogen peroxide induced cell cytotoxicity. The
      extract acted on IMR32 cells in a dose dependent manner as observed through PI
      and MTT assays. The percentage intracellular ROS activity was reduced by 60-70%
      in treated cells compared to H2O2 control. CONCLUSION: Thus the outcome of the
      study suggests that H. rhamnoides acts as a neuroprotectant against oxidative
      stress induced neurodegeneration.

PMID- 26288572
TI  - Molecular application for identification of polycyclic aromatic hydrocarbons
      degrading bacteria (PAHD) species isolated from oil polluted soil in Dammam, Saud
      Arabia.
AB  - Soil contamination with petroleum hydrocarbon products such as diesel and engine
      oil is becoming one of the major environmental problems. This study describes
      hydrocarbons degrading bacteria (PHAD) isolated from long-standing petrol
      polluted soil from the eastern region, Dammam, Saudi Arabia. The isolated strains
      were firstly categorized by accessible shape detection, physiological and
      biochemistry tests. Thereafter, a technique established on the sequence analysis
      of a 16S rDNA gene was used. Isolation of DNA from the bacterial strains was
      performed, on which the PCR reaction was carried out. Strains were identified
      based on 16S rDNA sequence analysis, As follows amplified samples were
      spontaneously sequenced automatically and the attained results were matched to
      open databases. Among the isolated bacterial strains, S1 was identified as
      Staphylococcus aureus and strain S1 as Corynebacterium amycolatum. 

PMID- 26288573
TI  - Morphological and physiological characterization of different genotypes of faba
      bean under heat stress.
AB  - Heat stress (HS) is the major constraint to crop productivity worldwide. The
      objective of the present experiment was to select the tolerant and sensitive
      genotype(s) on the basis of morpho-physiological and biochemical characteristics
      of ten Vicia faba genotypes. These genotypes were as follows: Zafar 1, Zafar 2,
      Shebam 1, Makamora, Espan, Giza Blanka, Giza 3, C4, C5 and G853. The experimental
      work was undertaken to study the effects of different levels of temperature
      (control, mild, and modest) on plant height (PH) plant(-1), fresh weight (FW) and
      dry weight (DW) plant(-1), area leaf(-1), content of leaf relative water (RWC),
      proline content (Pro) and total chlorophyll (Total Chl), electrolyte leakage
      (EL), malondialdehyde level (MDA), hydrogen peroxide (H2O2), and activities of
      catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD) enzymes. HS
      significantly affected growth performance of all genotypes. However, the
      magnitude of reduction in genotypes 'C5' was relatively low, possibly due to its
      better antioxidant activities (CAT, POD and SOD), and accumulation of Pro and
      Total Chl, and leaf RWC. In the study, 'C5' was noted to be the most HS tolerant
      and 'Espan' most HS sensitive genotypes. It was concluded that the heat-tolerant
      genotypes may have better osmotic adjustment and protection from free radicals by
      increasing the accumulation of Pro content with increased activities of
      antioxidant enzyme. 

PMID- 26288574
TI  - Cost-effectiveness of tiotropium versus usual care and glycopyrronium in the
      treatment of chronic obstructive pulmonary disease in Sweden.
AB  - BACKGROUND: Tiotropium (TIO) is a well-established bronchodilator, LAMA (long
      acting anticholinergic), for the treatment of moderate to very severe chronic
      obstructive pulmonary disease (COPD). Clinical evidence suggests that tiotropium
      is superior to usual non-LAMA care (UC) but may also have benefits compared to
      other LAMAs in preventing and limiting the effects of severe exacerbations. The
      primary objective of this study was to undertake a cost-effectiveness analysis of
      adding tiotropium to usual care versus usual care alone. A secondary objective
      was to assess the cost-effectiveness of tiotropium compared to glycopyrronium
      (GLY), another LAMA. The study was conducted with a Swedish setting in mind.
      METHODS: A Markov cohort model, incorporating the effects of exacerbations, was
      populated with efficacy data from the UPLIFT and SPARK trials and epidemiological
      data relevant for a Swedish patient population. Treatment efficacy of tiotropium
      was modelled as a lowering of the risk of exacerbations and as a slow-down of
      overall disease progression. The model followed patients over their remaining
      life-time. RESULTS: The base case analysis showed that patients treated with
      tiotropium gained 0.07 quality-adjusted life years (QALYs) compared to usual care
      alone at an incremental cost of SEK 15,041, resulting in a cost per QALY gained
      of SEK 224,850. Compared to glycopyrronium the QALY gained was estimated to 0.23
      QALYs in favour of tiotropium at an incremental cost of SEK 2423, yielding a cost
      per QALY gained of SEK 10,456. The results were mainly driven by differences in
      the risk of severe exacerbations. CONCLUSION: At the current implicit willingness
      to-pay (WTP) per QALY threshold in Sweden, the results from this study indicate
      that tiotropium is a highly cost-effective intervention when added to usual non
      LAMA care in the treatment of moderate to very severe COPD in Sweden. In
      addition, tiotropium is a highly cost-effective intervention when compared to
      glycopyrronium monotherapy.

PMID- 26288576
TI  - Colorectal Adenoma - Resection Techniques and Surveillance.

PMID- 26288575
TI  - Plausible ergogenic effects of vitamin D on athletic performance and recovery.
AB  - The purpose of this review is to examine vitamin D in the context of sport
      nutrition and its potential role in optimizing athletic performance. Vitamin D
      receptors (VDR) and vitamin D response elements (VDREs) are located in almost
      every tissue within the human body including skeletal muscle. The hormonally
      active form of vitamin D, 1,25-dihydroxyvitamin D, has been shown to play
      critical roles in the human body and regulates over 900 gene variants. Based on
      the literature presented, it is plausible that vitamin D levels above the normal
      reference range (up to 100 nmol/L) might increase skeletal muscle function,
      decrease recovery time from training, increase both force and power production,
      and increase testosterone production, each of which could potentiate athletic
      performance. Therefore, maintaining higher levels of vitamin D could prove
      beneficial for athletic performance. Despite this situation, large portions of
      athletic populations are vitamin D deficient. Currently, the research is
      inconclusive with regards to the optimal intake of vitamin D, the specific forms
      of vitamin D one should ingest, and the distinct nutrient-nutrient interactions
      of vitamin D with vitamin K that affect arterial calcification and
      hypervitaminosis. Furthermore, it is possible that dosages exceeding the
      recommendations for vitamin D (i.e. dosages up to 4000-5000 IU/day), in
      combination with 50 to 1000 mcg/day of vitamin K1 and K2 could aid athletic
      performance. This review will investigate these topics, and specifically their
      relevance to athletic performance. 

PMID- 26288577
TI  - Epidemiology of Colorectal Adenomas and Histopathological Assessment of
      Endoscopic Specimens in the Colorectum.
AB  - BACKGROUND: Colorectal cancer is one of the most frequently observed neoplasms in
      the world. It develops from intraepithelial neoplasia of the colorectal mucosa,
      and these precursor lesions are also known as adenoma. As the precursor lesion is
      known and can be detected easily, efficient screening strategies are available
      for a reliable prevention of colorectal adenocarcinoma, e.g. by colonoscopy.
      METHODS: Literature databases (PubMed) were searched selectively for the keywords
      'colorectal adenoma', 'epidemiology', and 'resection techniques'. The results are
      presented in the following text, also taking into account our own experience and
      the current S3 guidelines. RESULTS: Endoscopic resection samples are one of the
      specimens most frequently assessed by pathologists. Therefore,
      gastroenterologists expect standardized and well-structured pathology reports,
      stating relevant information concerning the removed lesions and recommendations
      for clinical management. These aspects are summarized in the evidence-based S3
      guideline. CONCLUSION: As a consequence of colorectal adenoma resection during
      screening procedures, the carcinoma incidence is decreasing. For further
      advancements in successful prevention, knowledge of different precursor lesions
      (conventional adenoma, serrated adenoma) is important, but also structured
      communication between the different disciplines engaged in colorectal cancer
      screening.

PMID- 26288578
TI  - Competition in Colon Cancer Screening? What Is the Role of Colonoscopy?
AB  - BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of cancer
      related death in the Western world. The incidence could be reduced if this cancer
      were to be diagnosed at an early stage of disease. A competition has started
      between the existing screening methods to be the most efficient in detecting
      premalignant conditions. This review illustrates the current state of screening
      techniques for CRC. METHOD: Pubmed was searched for meta-analyses and prospective
      studies on screening for CRC, with an emphasis on colonography, computed
      tomographic colonography (CTC), magnetic resonance colonography (MRC), stool DNA
      testing, and colon capsule endoscopy, and critical appraisal of the research was
      done by the reviewers. RESULTS: The imaging techniques (CTC and MRC) had similar
      detection rates for bigger lesions (>=10 mm) as colonoscopy. High-definition
      colonoscopy showed better efficiency with smaller lesions. The techniques
      developing around colonoscopy such as the retro-viewing colonoscope, the balloon
      colonoscope, or the 330-degree viewing colonoscope try to enhance efficacy by
      reducing the adenoma miss rate in right-sided, non-polypoid lesions. Colon
      capsule endoscopy and the stool detection systems are limited to identifying
      cancer but not necessarily adenomas. CONCLUSION: Colonoscopy is the preferred CRC
      screening strategy and the undisputed gold standard in terms of efficacy.

PMID- 26288579
TI  - What Influences the Quality of Prevention Colonoscopy?
AB  - BACKGROUND: Colorectal cancer still has a high incidence and mortality. Although
      colonoscopy is considered as gold standard of colorectal cancer screening, there
      still exists an unsatisfactory level of adenomas missed in screening and
      surveillance colonoscopy. Furthermore, patients bear the burden of potentially
      unpleasant and painful examination and preparation procedures. METHOD: A search
      of the literature using PubMed was carried out, supplemented by a review of the
      programs of the Digestive Disease Week (DDW) and the United European
      Gastroenterology Week (UEGW) 2011-2013. RESULTS: Several new approaches to
      colonoscopy were described: water, CO2 and cap colonoscopy, and application of
      spasmolytics such as hyoscine butylbromide and glucagon. The use of these methods
      does not necessitate the purchase of new endoscopes. They are feasible and safe,
      facilitate achieving the aim of more comfort and less pain, and perhaps allow
      lower doses of sedatives to be used. However, a clear effect on procedure time is
      lacking. Furthermore, the published data do not consistently answer the question
      of whether these techniques have a positive impact on the most important goal,
      the better detection of carcinoma precursors. CONCLUSION: More efforts to
      optimize bowel preparation have to be made to improve visualization of the
      mucosal surface. The most reliable criteria for the quality of screening and
      surveillance colonoscopy remain a minimum cecal intubation rate of >90%, a
      withdrawal time of at least 6 or better 9 min, and an adenoma detection rate of
      >20%. These results should be achieved with a complication rate lower than 1%,
      including polypectomy.

PMID- 26288580
TI  - Endoscopic Submucosal Dissection (ESD) in Colorectal Tumors.
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) - initially developed for the
      treatment of early gastric cancer in Japan - is an attractive option for en bloc
      resection of larger sessile or flat colorectal neoplasia. METHODS: A review of
      the current literature on colorectal ESD was carried out. RESULTS: In contrast to
      conventional endoscopic mucosal resection (EMR), ESD for larger colorectal
      neoplasia yields high en bloc resection rates and very low recurrence rates. The
      frequency of delayed bleeding is similar for EMR and ESD. Higher perforation
      rates during ESD are mostly due to microperforations identified and treated
      during the intervention, and are therefore of minor clinical relevance. A major
      disadvantage of ESD is the necessity for high-level endoscopic skills and long
      procedure times. ESD also has the potential to replace laparoscopic surgery or
      transanal endoscopic microsurgery mainly due to its lower complication rates.
      CONCLUSION: ESD for the resection of larger flat or sessile colorectal lesions
      has potential advantages over conventional EMR or minimally invasive surgery. Due
      to the low incidence of early gastric cancer, experience with ESD will remain
      limited in Western countries. The spread of colorectal ESD will depend on
      adequate training opportunities and also on modifications yielding a reduction in
      procedure time.

PMID- 26288581
TI  - Is There an Indication for Surgical Resection in Colorectal Adenoma?
AB  - BACKGROUND: Due to the adenoma-carcinoma sequence, complete removal of colorectal
      polyps is essential. METHOD: This article analyzes the role of surgery in the
      removal of colorectal adenoma. RESULTS: Nowadays, most adenomas are removed
      properly by endoscopic methods. Also in the resection of giant polyps and
      recurrent adenoma endoscopic data is convincing. Therefore, surgical resection of
      colorectal adenomas is required in the case of endoscopic inaccessibility.
      Reasons for this may be the location of the polyp, incomplete endoscopic
      resection, or suspected malignancy. Endoscopic or limited surgical resection of
      malignant adenomas is acceptable only if 'low-risk' criteria are fulfilled.
      Otherwise oncologic radical resection is recommended. In general, radical
      resection is also necessary in the case of polyps that are not suitable for
      endoscopic removal, because here the rate of colorectal carcinoma is high.
      CONCLUSION: If a surgical approach is necessary, minimally invasive surgery in
      the hands of an experienced laparoscopic surgeon is a suitable option. Adenomas
      in the lower two thirds of the rectum are suitable for transanal full-thickness
      resection. This is done by conventional resection or transanal endoscopic
      microsurgery. The histopathological preparation of these specimens provides
      diagnostic and therapeutic benefits, particularly compared to piecemeal resection
      of early carcinoma.

PMID- 26288582
TI  - Gender-Specific Aspects of Lynch Syndrome and Familial Adenomatous Polyposis.
AB  - BACKGROUND: The most frequent hereditary colorectal cancer (CRC) syndromes are
      Lynch syndrome and familial adenomatous polyposis (FAP), accounting for
      approximately 5% of the CRC burden. Both are characterized by an autosomal
      dominant mode of transmission and require an individualized approach of
      intensified screening and prophylactic surgery. METHODS: In this review, we
      provide an overview of the literature regarding gene- and gender-specific aspects
      of Lynch syndrome and FAP. Based upon available data, a personalized approach
      when treating patients and families with these predisposition syndromes is
      increasingly warranted. RESULTS: In Lynch syndrome patients, men have a
      significantly higher lifetime risk and earlier age of manifestation for CRC -
      especially in MSH6 mutation carriers. Moreover, incidence of gastric, bladder,
      and urothelial cancers is much higher in males. Females with an MSH6 mutation
      have to be aware of a very high risk especially for endometrial, but also for
      ovarian cancer. In FAP families, females are more prone to papillary thyroid
      cancers and also to desmoid tumors. CONCLUSION: It is timely to suggest gene- and
      gender-based adapted screening and surgical recommendations for Lynch syndrome
      patients. In FAP patients, females should follow intensified screening
      recommendations for early detection of precursors or papillary cancer of the
      thyroid. Moreover, desmoid patients should primarily not be subjected to surgical
      resection but rather to a gender-specific conservative medical treatment.

PMID- 26288583
TI  - Gender-Specific Effects on Immune Response and Cardiac Function after Trauma
      Hemorrhage and Sepsis.
AB  - BACKGROUND: Studies in human as well as animal models indicate a gender-specific
      responsiveness of the immune and organ systems with regard to shock, trauma, and
      sepsis. METHODS: A literature review was performed. RESULTS: Cell-mediated immune
      responses and cardiovascular functions are suppressed in males following trauma
      hemorrhage, whereas they are maintained or even enhanced in females in the
      proestrus state of the estrus cycle. Experimental studies have demonstrated that
      divergent immune responses in males and females following adverse circulatory
      conditions are mediated by the gender-specific hormones testosterone and
      estrogen. Several clinical trials, however, failed to demonstrate a significant
      association of gender and inflammatory response. This may be explained by the
      heterogeneity of the population in terms of their hormonal status at the time of
      injury. CONCLUSIONS: With regard to the underlying mechanisms, receptors for sex
      hormones have been identified on various immune cells, suggesting direct effects
      of these hormones on immune function. Alternatively, indirect effects of sex
      steroids such as changes in cardiovascular responses or androgen- and estrogen
      synthesizing enzymes might contribute to gender-specific immune responses.
      Clinical studies suggest that sex hormones, such as dehydroepiandrosterone,
      modulate the function of peripheral blood mononuclear cells also following
      abdominal surgery. Thus, sex hormones, receptor antagonists, and sex steroid
      synthesizing enzymes might be useful in the future for modulating the complex
      immune responses after trauma hemorrhage and sepsis.

PMID- 26288585
TI  - Gender-Specific Differences in Surgical Site Infections: An Analysis of 438,050
      Surgical Procedures from the German National Nosocomial Infections Surveillance
      System.
AB  - BACKGROUND: Surgical site infections (SSI) are among the most frequent healthcare
      associated infections. They impose a substantial burden with increased morbidity
      and exceeding healthcare costs. Risk factors such as age, diabetes, and smoking
      status are commonly accounted for in the literature, but few studies address
      gender differences. METHODS: Data from the German Nosocomial Infections
      Surveillance System (Krankenhaus-Infektions-Surveillance-System (KISS)) from 2005
      to 2010 were analysed for cardiac, vascular, visceral, and orthopaedic surgery,
      with a total of 438,050 surgical procedures and 8,639 SSI. Rates of SSI and
      isolated pathogens were analysed for gender. RESULTS: Women had a lower rate of
      SSI (SSI/100 procedures) in abdominal surgery than men (2.92 vs. 4.37; p <
      0.001). No gender-specific differences were found in orthopaedic and vascular
      surgery, while women had a higher risk for SSI in cardiac surgery (5.50 vs. 3.02;
      p < 0.001). Isolated pathogens showed differences for sensitive Staphylococcus
      aureus and Pseudomonas aeruginosa, which were more frequent in women (both p =
      0.007), while coagulase-negative staphylococci occurred more often in men (18.8
      vs. 14.0%; p < 0.001). CONCLUSION: Gender differences in SSI exist and are
      procedure-specific. The underlying mechanisms need to be further elucidated so
      that targeted measures for the prevention of SSI can be developed.

PMID- 26288584
TI  - Applying the Gender Lens to Risk Factors and Outcome after Adult Cardiac Surgery.
AB  - BACKGROUND: Applying the gender lens to risk factors and outcome after adult
      cardiac surgery is of major clinical interest, as the inclusion of sex and gender
      in research design and analysis may guarantee more comprehensive cardiovascular
      science and may consecutively result in a more effective surgical treatment as
      well as cost savings in cardiac surgery. METHODS: We have reviewed classical
      cardiovascular risk factors (diabetes, arterial hypertension, hyperlipidemia,
      smoking) according to a gender-based approach. Furthermore, we have examined
      comorbidities such as depression, renal insufficiency, and hormonal influences in
      regard to gender. Gender-sensitive economic aspects have been evaluated, surgical
      outcome has been analyzed, and cardiovascular research has been considered from a
      gender perspective. RESULTS: The influence of typical risk factors and outcome
      after cardiac surgery has been evaluated from a gender perspective, and the
      gender-specific distribution of these risk factors is reported on. The named
      comorbidities are listed. Economic aspects demonstrated a gender gap. Outcome
      after coronary and valvular surgeries as well as after heart transplantation are
      displayed in this regard. Results after postoperative use of intra-aortic balloon
      pump are shown. Gender-related aspects of clinical and biomedical cardiosurgical
      research are reported. CONCLUSIONS: Female gender has become an independent risk
      factor of survival after the majority of cardiosurgical procedures. Severely
      impaired left ventricular ejection fraction independently predicts survival in
      men, whereas age does in females.

PMID- 26288586
TI  - Prospective Analysis of More than 1,000 Patients with Rectal Carcinoma: Are There
      Gender-Related Differences?
AB  - BACKGROUND: Since the beginning of the new millennium gender medicine has become
      more and more relevant. The goal has been to unveil differences in presentation,
      treatment response, and prognosis of men and women with regard to various
      diseases. METHODS: This study encompassed 1,061 patients who underwent surgery
      for rectal cancer at the Department of Surgery, University Medical Center
      Schleswig-Holstein Campus Lubeck, Germany, between January 1990 and December
      2011. Prospectively documented demographic, clinical, pathological, and follow-up
      data were obtained. Analysis encompassed the comparison of clinical,
      histopathological, and oncological parameters with regard to the subcohorts of
      male and female patients. RESULTS: No statistically significant differences could
      be found for clinical and histopathological parameters, location of tumor,
      resection with or without anastomosis, palliative or curative treatment,
      conversion rates, duration of surgery, and long-term survival. For the entire
      cohort, gender-related statistically significant differences in complications
      encompassed anastomotic leakage, burst abdomen, pneumonia, and urinary tract
      complications all of which occurred more often in men. CONCLUSION: Data obtained
      in this study suggest that there are no gender-related differences in the
      oncologic surgical treatment of patients with rectal carcinoma. However, male sex
      seems to be a risk factor for increased early postoperative morbidity.

PMID- 26288587
TI  - Are There Gender-Specific Aspects in Obesity and Metabolic Surgery? Data Analysis
      from the German Bariatric Surgery Registry.
AB  - BACKGROUND: Since January 2005, the status of bariatric surgery in Germany has
      been examined in conjunction with a quality assurance study of the German
      Bariatric Surgery Registry (GBSR). All data are registered prospectively in
      cooperation with the Institute for Quality Assurance in Surgical Medicine at the
      Otto-von-Guericke University Magdeburg, Germany. METHODS: Data are registered in
      an online database. Data collection on obesity and metabolic surgery is
      voluntary, and was started in 2005. In addition, follow-up data are collected
      once a year. RESULTS: Since 2005, 8,293 sleeve gastrectomies, 10,330 Roux-en-Y
      gastric bypass procedures, and 3,741 gastric banding procedures have been
      performed in Germany, according to the data of the GBSR. Mean age and mean body
      mass index of female patients with gastric banding, sleeve gastrectomy, or Roux
      en-Y gastric bypass were significantly lower than those of male patients. The
      incidence of relevant comorbidities was significantly higher in male than in
      female patients. CONCLUSION: Metabolic and obesity surgery is becoming more and
      more popular in Germany. Data from the GBSR study show significant differences in
      preoperative comorbidities and postoperative complication and mortality rates
      between male and female patients. There is a need for further evaluation of
      gender-specific aspects to optimize patient selection and reduce specific
      postoperative complications.

PMID- 26288588
TI  - The Pathophysiology of Malabsorption.
AB  - Physiological digestion and absorption of nutrients within the gastrointestinal
      tract requires a complex interaction between motor, secretory, digestive, and
      absorptive functions that is vulnerable to a multitude of potential disturbances
      which may lead to global or specific malabsorption syndromes. Potential
      pathomechanisms that are illustrated in this article include insufficient
      mechanical breakdown of harder food components due to chewing problems and/or
      decreased antral contractility, critical reduction of time for absorption in
      patients with markedly enhanced upper gastrointestinal transit (e.g. dumping
      syndrome), impaired digestion and absorption of nutrient components caused by
      reduced gastric acid secretion, pancreatic exocrine insufficiency or reduced
      biliary secretion, defects of the enteral mucosa with enzyme deficiencies (e.g.
      disaccharidases) or lack of specific carrier mechanisms (e.g. hexose or aminoacid
      transporters), and critical quantitative loss of intestinal mucosa in patients
      with short bowel syndrome. 

PMID- 26288590
TI  - Whipple's Disease.
AB  - BACKGROUND: Whipple's disease (WD) is rarely the cause of a malabsorption
      syndrome. The disease is a chronic infection of the intestinal mucosa with the
      bacterium Tropheryma whipplei, which leads to a lymphostasis with an impaired
      absorption of the nutrition. Due to its low incidence (1:1,000,000) and the non
      specific early symptoms, the disease is often diagnosed only after many years.
      METHODS: Based on a selective literature review and the clinical experience of
      the authors, the current knowledge of WD regarding pathogenesis, clinical
      presentation, diagnosis, and therapy are presented in this paper. RESULTS: Recent
      studies suggest that a host-specific dysfunction of the intestinal macrophages is
      responsible for the chronic infection with T. whipplei. Prior to patients
      reporting symptoms of a malabsorption syndrome (chronic diarrhea/steatorhea,
      weight loss), they often suffer from non-specific symptoms (polyarthralgia,
      fever, fatigue) for many years. Misdiagnoses such as seronegative polyarthritis
      are frequent. Furthermore, neurological, cardiac, ocular, or dermatological
      symptoms may occur. The standard method concerning diagnosis is the detection of
      PAS(periodic acid-Schiff)-positive macrophages in the affected tissues.
      Immunohistochemical staining and PCR(polymerase chain reaction)-based genetic
      analysis increase the sensitivity and specificity of conventional detection
      methods. Endoscopically, the intestinal mucosa appears edematous with
      lymphangiectasias, enlarged villi, and white-yellowish ring-like structures. The
      German treatment recommendations include a two-week intravenous induction therapy
      with ceftriaxone, which is followed by a three-month oral maintenance therapy
      with trimethoprim/sulfamethoxazole. CONCLUSION: WD is rarely responsible for a
      malabsorption syndrome. However, if WD is not recognized, the disease can be
      lethal. New diagnostic methods and prospectively approved therapeutic concepts
      allow an adequate treatment of the patient. Due to the host-specific
      susceptibility to T. whipplei, a lifelong follow-up is necessary.

PMID- 26288589
TI  - Coeliac Disease - New Pathophysiological Findings and Their Implications for
      Therapy.
AB  - Coeliac disease (CD) is one of the most common diseases worldwide, resulting from
      a combination of environmental (gluten) and genetic (human leucocyte antigen
      (HLA) and non-HLA genes) factors. Depending on the geographical location, the
      prevalence of CD has been estimated to approximate 0.5-1%. The only treatment
      currently available for CD is a gluten-free diet (GFD) excluding gluten
      containing cereals such as wheat, rye, and barley, and other foodstuffs with
      natural or added gluten. However, adherence rates and patient acceptance are
      often poor. Moreover, even in fully adherent patients, the diet may fail to
      induce clinical or histological improvement. Hence, it is unsurprising that
      studies show CD patients to be highly interested in non-dietary alternatives. The
      following review focuses on current pathophysiological concepts of CD,
      spotlighting those pathways which may serve as new possible, non-dietary
      therapeutic targets in the treatment of CD. 

PMID- 26288591
TI  - Short Bowel Syndrome and Malabsorption - Causes and Prevention.
AB  - BACKGROUND: The short bowel syndrome (SBS) is a condition caused by extensive
      intestinal resection for a variety of conditions. The etiology varies by age
      group. Necrotizing enterocolitis is the leading cause in infants. In older
      children, trauma and malignancies are most common. Postoperative SBS has become
      most common in adults, followed by mesenteric vascular disease and
      cancer/irradiation. METHODS: Systematic literature review. RESULTS: Prevention of
      SBS should be given high priority. Each of the etiologies has been evaluated and
      strategies to prevent extensive resection have been developed. These include a
      thoughtful approach to reoperation, early identification of complications, e.g.
      intestinal ischemia, reducing radiation enteritis, and bowel-conserving therapies
      in diseases such as Crohn's disease. CONCLUSION: Several operative strategies to
      prevent SBS are useful. Timing and extent of reoperation need careful
      consideration. Minimizing intestinal resection, bowel-conserving techniques for
      complications such as fistula or strictures, and remodeling procedures are
      important.

PMID- 26288592
TI  - The Surgical Approach to Short Bowel Syndrome - Autologous Reconstruction versus
      Transplantation.
AB  - BACKGROUND: Short bowel syndrome (SBS) is a state of malabsorption resulting from
      massive small bowel resection leading to parenteral nutrition (PN) dependency.
      Considerable advances have been achieved in the medical and surgical management
      of SBS over the last few decades. METHODS: This review discusses in detail the
      surgical approach to SBS. RESULTS: Widespread use of PN enables long-term
      survival in patients with intestinal failure but at the cost of PN-associated
      life-threatening complications including catheter-associated blood stream
      infection, venous thrombosis, and liver disease. The goal of management of
      intestinal failure due to SBS is to enable enteral autonomy and wean PN by means
      of a multi-disciplinary approach. Availability of modified enteral feeding
      formulas have simplified nutrition supplementation in SBS patients. Similarly,
      advances in the medical field have made medications like growth hormone and
      glucagon-like peptide (GLP2) available to improve water and nutrient absorption
      as well as to enable achieving enteral autonomy. Autologous gastrointestinal
      reconstruction (AGIR) includes various techniques which manipulate the bowel
      surgically to facilitate the bowel adaptation process and restoration of enteral
      nutrition. Ultimately, intestinal transplantation can serve as the last option
      for the cure of intestinal failure when selectively applied. CONCLUSION: SBS
      continues to be a challenging medical problem. Best patient outcomes can be
      achieved through an individualized plan, using various AGIR techniques to
      complement each other, and intestinal transplantation as a last resort for cure.
      Maximum benefit and improved outcomes can be achieved by caring for SBS patients
      at highly specialized intestinal rehabilitation centers.

PMID- 26288593
TI  - The Pancreas: Causes for Malabsorption.
AB  - BACKGROUND: The pancreas has a central function in digestion and glucose
      homeostasis. With regard to the exocrine function, which is responsible for the
      digestion and absorption of nutrients and vitamins, the most important
      disturbances of these physiological processes are based on deficiencies in enzyme
      production and secretion, either due to impaired excretion caused by obstruction
      of the pancreatic duct or due to loss of pancreatic tissue. Both conditions
      result in maldigestion, malabsorption, and malnutrition. METHODS: Systematic
      literature review. RESULTS: Symptoms associated with pancreatic exocrine failure
      are gastrointestinal discomfort, steatorrhea, and weight loss. Pancreatic
      exocrine insufficiency caused by ductal obstruction occurs in chronic
      pancreatitis or with neoplasia of the pancreatic head. Loss of functional
      parenchyma can be caused either by chronic pancreatitis resulting in fibrotic
      replacement of the destroyed parenchyma or by a postoperative state of pancreatic
      resection. CONCLUSION: In patients with chronic pancreatitis, a stage-adapted and
      timely therapy including conservative as well as surgical measures is essential
      to prevent functional deterioration and to preserve residual function. In the
      case of pancreatic resection for chronic pancreatitis, this can be achieved with
      modern organ-sparing surgery such as the duodenum-preserving pancreatic head
      resection. In patients requiring more extended pancreatic resections and even
      total duodenopancreatectomy, regardless of the underlying indication, adequate
      enzyme replacement and monitoring of the nutritional status is critical to
      prevent impairment of quality of life as well as detrimental malnutrition in the
      long term.

PMID- 26288594
TI  - Malabsorption as a Therapeutic Approach in Bariatric Surgery.
AB  - BACKGROUND: The increasing prevalence of obese patients will lead to a more
      frequent use of bariatric procedures in the future. Compared to conservative
      medical therapy, bariatric procedures achieve greater weight loss and superior
      control of comorbidities, resulting in improved overall mortality. METHODS: A
      search for current literature regarding mechanisms, indications, and outcomes of
      bariatric surgery was performed. RESULTS: In order to care for patients after
      bariatric surgery properly, it is important to understand its mechanisms of
      action and effects on gastrointestinal physiology. Recent investigations indicate
      that the beneficial effects of bariatric procedures are much more complex than
      simply limiting food intake or an associated malabsorption. Changes in
      gastrointestinal hormone secretion, energy expenditure, intestinal bacterial
      colonization, bile acid metabolism, and epigenetic modifications resulting in
      altered gene expression are likely responsible for the majority of the beneficial
      effects of bariatric surgery. Malabsorptive bariatric procedures divert the flow
      of bile and pancreatic enzymes from food and therefore limit the digestion and
      absorption of nutrients, resulting in reduced calorie intake and subsequent
      weight loss. Essential micronutrients such as vitamins and trace elements are
      also absorbed to a lesser extent, potentially leading to severe side effects.
      CONCLUSION: To prevent malnutrition, dietary supplementation and regular control
      of micronutrient levels are mandatory for patients undergoing malabsorptive
      bariatric procedures, in whom the fat-soluble vitamins A and D are commonly
      deficient.

PMID- 26288595
TI  - Solid Pseudopapillary Neoplasm of the Pancreas: Analysis of Seven Cases.
AB  - BACKGROUND: The purpose of this study was to describe as well as compare our
      surgical treatment experiences of solid pseudopapillary neoplasms (SPN) of the
      pancreas and to provide a review of the literature. METHODS: A retrospective
      analysis of data from Vilnius University Hospital Santariskiu Klinikos (VUH SK)
      and of the literature, which was researched using Karger Publishers, Springer
      Science, BioMed Central, and disserCat databases, was conducted. RESULTS: From
      2001 to 2012, seven cases were identified with pathologically confirmed SPN
      diagnosis. A precise preoperative diagnosis was made by computertomography and
      magnetic resonance imaging. The median diameter of the tumors was 6.36 cm (range
      1.5-12 cm). Surgical treatment was undertaken for all patients. Results of the
      immunohistochemical analysis confirmed a nuclear accumulation of beta-catenin.
      The Ki-67 level was 1-2% in all of the cases. According to our collected data,
      all types of histological analysis revealed decent prognostic behavior with low
      mitotic activity (1-2 mitoses per 50 high power fields). Besides, angioinvasion,
      perineural invasion, and outside capsule invasion were not detected. CONCLUSIONS:
      There was no correlation between more aggressive types of SPN and tumor size,
      localization, age, and gender.

PMID- 26288596
TI  - Palliative Endoscopic Treatment Options in Malignancies of the Biliopancreatic
      System.
AB  - In most of the cases, pancreatic cancer and malignancies of the bile tract can
      only be treated palliatively. Endoscopy offers several methods for effective
      control of the symptoms in those situations. In pancreatic cancer, stenting of
      bile ducts enables a control of jaundice most of the time. Stenting of an
      obstructed duodenum can relieve symptoms of gastric outlet obstruction without
      the need for major surgery. In biliary tract cancer, stenting of the bile ducts
      can provide effective drainage of the biliary system. Photodynamic therapy and
      radiofrequency ablation can sometimes be a valuable tool in symptom control. This
      review tries to provide an overview on endoscopic palliative treatment options in
      pancreatic cancer and biliary tract cancer. 

PMID- 26288597
TI  - Extending the Frontiers Beyond Thermal Ablation by Radiofrequency Ablation: SBRT,
      Brachytherapy, SIRT (Radioembolization).
AB  - Metastatic spread of the primary is still defined as the systemic stage of
      disease in treatment guidelines for various solid tumors. This definition is the
      rationale for systemic therapy. Interestingly and despite the concept of systemic
      involvement, surgical resection as a local treatment has proven to yield long
      term outcomes in a subset of patients with limited metastatic disease, supporting
      the concept of oligometastatic disease. Radiofrequency ablation has yielded
      favorable outcomes in patients with hepatocellular carcinoma and colorectal
      metastases, and some studies indicate its prognostic potential in combined
      treatments with systemic therapies. However, some significant technical
      limitations apply, such as size limitation, heat sink effects, and unpredictable
      heat distribution to adjacent risk structures. Interventional and non-invasive
      radiotherapeutic techniques may overcome these limitations, expanding the options
      for oligometastatic patients and cytoreductive concepts. Current data suggest
      very high local control rates even in large tumors at any given location in the
      human body. The article focusses on the characteristics and possibilities of
      stereotactic body radiation therapy, interstitial high-dose-rate brachytherapy,
      and Yttrium-90 radioembolization. In this article, we discuss the differences of
      the technical preferences as well as their impact on indications. Current data is
      presented and discussed with a focus on application in oligometastatic or
      cytoreductive concepts in different tumor biologies. 

PMID- 26288598
TI  - Is There Any Evidence for a Role of Local Treatment in Cholangiocarcinoma?
AB  - BACKGROUND: Most cholangiocarcinomas (CCA) are locally advanced and unresectable
      at the time of diagnosis. Currently, chemotherapy combining gemcitabine with a
      platinum agent is the recommended first-line treatment regimen for advanced
      biliary tract cancer. However, median overall survival is only approximately 1
      year. As the hepatic tumor burden is the limiting factor for the prognosis of
      these patients, local tumor control is essential. METHODS: We present and discuss
      the current evidence for such therapy options for patients with CCA. RESULTS:
      Local and locoregional therapies have been shown to be well tolerated and can
      contribute to tumor control in the context of a comprehensive oncologic treatment
      strategy, and may prolong survival of patients with advanced CCA. Unfortunately,
      only few high-quality clinical trials are available. CONCLUSION: Randomized
      prospective clinical trials enrolling larger numbers of patients need to be
      carried out to elucidate the precise value of these treatments alone as well as
      in combination with systemic chemotherapy.

PMID- 26288599
TI  - How to Create Evidence for the Integration of Local and Locoregional Treatments
      in Future Oncological Treatment Concepts?
AB  - BACKGROUND: While local treatment using more innovative technologies is
      increasingly applied in contemporary treatment of advanced cancer, its impact on
      outcomes is not well understood. METHODS: We reviewed the literature using PubMed
      and major oncology congress websites, and report here about the understanding of
      oligometastatic disease, about the role of primary tumor resection in metastatic
      disease, and about the value of cytoreduction and tumor ablation. RESULTS: The
      Achilless' heel of local treatment is the current lack of evidence of its
      efficacy. When considering how this lack of knowledge can be overcome, we arrive
      at three suggestions: First, adequately powered clinical trials must be performed
      to allow for the proper assessment of differences in survival outcomes. Second,
      the effect of local treatment on the biological evolution of the disease needs to
      be studied; analysis of circulating tumor DNA may help to assess these effects.
      Third and foremost, patient-reported outcomes like quality of life, symptom
      control, and satisfaction with treatment should define when to use and when to
      omit local treatment. CONCLUSIONS: Innovative trial designs in future oncology
      research will be required for assessing the true value of local and locoregional
      therapy.

PMID- 26288600
TI  - Gastric Metastasis of Malignant Melanoma: Report of a Case and Review of
      Available Literature.
AB  - BACKGROUND: Malignant melanoma is a tumor with common lymphogenic or hematogenic
      metastasis. Metastasis to the gastric mucosa is uncommon. CASE REPORT: We present
      the case of a 43-year-old female patient with metastases of a malignant melanoma
      to the lesser curvature of the stomach. The primary malignant melanoma of the
      right breast was resected 2 years previously. CONCLUSION: Metastases to the
      gastric mucosa are rarely seen. Esophagogastroduodenoscopy should be performed in
      symptomatic patients to rule out metastatic disease. When R0 resection can be
      achieved, it should be undertaken in order to increase the overall prognosis of
      the patient.

PMID- 26288601
TI  - Complications after Loop Ileostomy Closure: A Retrospective Analysis of 132
      Patients.
AB  - BACKGROUND: Closure of a loop ileostomy is a relatively simple procedure although
      many studies have demonstrated high morbidity rates following it. Methods to
      reduce the number of complications, such as timing of closure or different
      surgical closure techniques, are investigated. The aim of this study was to
      evaluate the experience of the Abdominal Surgery Center at Vilnius University
      Hospital (VUH) 'Santariskiu klinikos' to review the complications after closure
      of loop ileostomy and to identify potential risk factors for postoperative
      complications. METHODS: Data from 132 patients who underwent closure of loop
      ileostomy from 2003 to 2013 at the Abdominal Surgery Center of VUH were
      collected, including demographics, causes of ileostomy formation, additional
      diseases, time from creation to closure of ileostomy, anastomotic technique,
      duration of the operation, postoperative complications, and hospital stay after
      surgery. The operations were performed by 15 surgeons with varying experience
      assisted by surgical residents. Experience in ileostomy closure was defined by
      the number of procedures performed. RESULTS: Complications occurred in 24
      patients (18.2%), with 20 of them having surgical complications: bowel
      obstruction (9 (6.8%)), wound infection (4 (3.0%)), peritonitis due to
      anastomotic leak (3 (2.3%)), intra-abdominal abscess (2 (1.5%)), anastomotic leak
      with enterocutaneous fistula (1 (0.76%)), and bleeding (1 (0.76%)). 4 patients
      had non-surgical complications: postoperative diarrhea (2 (1.5%)), urinary
      retention (1 (0.76%)), and deep vein thrombosis (1 (0.76%)). Most complications
      were classified as group II according to the Clavien-Dindo classification. 2
      patients died (1.5%). The anastomotic technique used did not affect the outcome.
      The experience of the surgeon as judged by the frequency of the procedure was the
      main factor affecting postoperative morbidity significantly (p = 0.03).
      CONCLUSION: Our study revealed that the rate of postoperative complications and a
      smooth postoperative course after the closure of ileostomy was influenced by
      surgical experience.

PMID- 26288603
TI  - Management of Portal/Mesenteric Vein Thrombosis.

PMID- 26288602
TI  - Infections and Chronic Inflammatory Bowel Disease.
AB  - In the more recent years since the introduction of anti-TNF therapy, the
      treatment strategy in chronic inflammatory bowel disease has developed more
      towards an early intensive, often double immunosuppression. While this leads to
      an improved therapeutic success, this intensified therapy also increases the risk
      for side effects and especially for infectious complications. The early detection
      of this complication in the immunocompromised patient is often more difficult due
      to the potential broad spectrum of infectious agents, the often atypical
      presentation in conjunction with the immunosuppression as well as often similar
      symptoms regarding intestinal infectious complications common for a flare of the
      underlying disease. In the first part, this overview will discuss the broad
      spectrum of potential infectious complications, using pulmonary infections as an
      example and presenting an algorithm for detection and therapy. In the second
      part, common intestinal infectious complications will be discussed from diagnosis
      to therapy. 

PMID- 26288604
TI  - Etiology and Complications of Portal Vein Thrombosis.
AB  - BACKGROUND: Portal venous occlusion represents a disorder with considerable
      clinical relevance. The underlying causes of portal vein thrombosis (PVT) are
      frequently multifactorial and include malignancies, progressive chronic liver
      diseases, processes localized to the epigastrium and hepatobiliary system, and
      acquired as well as inherited thrombophilia. The three main categorical groups
      are malignant thrombosis, cirrhotic PVT, and non-malignant, non-cirrhotic PVT.
      METHODS: Review of the literature. RESULTS: The site, the extent, its chronicity,
      and the course of thromboses characterize a relatively heterogeneous clinical
      presentation and the ensuing complications in affected patients. While the
      occlusion of the extrahepatic portal and splenic vein likely provokes mainly
      complications related to portal hypertension, mesenteric venous obstruction shows
      a high rate of complications and mortality due to intestinal infarction.
      Especially in patients with liver cirrhosis, special care is warranted with
      regard to PVTs due to their pathogenetic role and influence on patient survival.
      CONCLUSION: This article aims to summarize the current opinion on etiologies,
      risk factors, and complications of this heterogeneous condition in adults.

PMID- 26288605
TI  - Radiological Diagnosis of Portal/Mesenteric Vein Occlusion.
AB  - BACKGROUND: In contrast to an acute occlusion of the visceral arteries, which is
      the most important differential diagnosis for an occlusion of the portal venous
      system and which poses a highly dangerous situation ending in gangrene of the
      bowel wall, the symptoms of an acute occlusion of the portal venous system are
      quite unspecific. To rule out an acute arterial occlusion, diagnostic evaluation
      has to be carried out quickly in order to decide on the necessity of therapeutic
      steps concerning a recanalization of the occluded vessels. Only few therapeutic
      options are available to recanalize and remodel the portal venous system,
      depending on the underlying disease, the age of the occlusion, its extension, and
      the effect on the bowel wall, stomach, spleen, and abdominal wall. Moreover, the
      efficacy of recanalization procedures mainly depends on the formation and number
      of collateral venous blood supply, its degree, and the anatomic structure.
      Possible complications of portal hypertension like varices, gastrointestinal
      vasculopathy, ascites, and splenomegaly also influence the success of
      recanalization procedures. Only in cases of acute thrombotic occlusion systemic
      lytic therapy promises to be successful. Therefore, other options such as
      transjugular intrahepatic recanalization, e.g. by means of the TIPS (transjugular
      intrahepatic portosystemic shunt) procedure, have to be evaluated. METHODS:
      Review of the literature. RESULTS: Noninvasive methods such as ultrasound (US),
      computed tomography, and especially magnetic resonance imaging (MRI) allow the
      evaluation of therapeutic options as well as their success, the feasibility of
      technical procedures, the detection of possible risks, and a calculation of risks
      and benefits. CONCLUSION: In order to arrive at the correct therapeutic decision,
      a combination of MRI and US methods combined with color Doppler guarantee the
      most efficient diagnostic results in cases with acute or chronic occlusions of
      the portal venous system.

PMID- 26288606
TI  - Nonsurgical Therapeutic Options in Portal Vein Thrombosis.
AB  - BACKGROUND: Portal vein thrombosis (PVT) is a rare but severe vascular disorder
      with an acute and a chronic course. Most patients have underlying liver
      cirrhosis; furthermore, thrombophilia is an important risk factor. However,
      idiopathic forms are also known. METHODS: This review discusses nonsurgical
      treatment options in PVT. RESULTS AND CONCLUSION: Therapy of acute PVT is based
      on anticoagulation with heparin that is switched to oral anticoagulants, if
      applicable. Catheter-guided invasive therapy should be considered; however,
      patients with liver cirrhosis should be screened for portal hypertension before
      anticoagulation is mandatory. Therapy of chronic PVT is discussed
      controversially; therefore, a strict patient selection and an individual
      therapeutic decision are warranted depending on the etiology of PVT. Special
      forms of PVT including septic and malignant thrombosis as well as PVT in patients
      waiting for liver transplantation require particular therapy algorithms.

PMID- 26288607
TI  - Therapy Algorithm for Portal Vein Thrombosis in Liver Cirrhosis: The Internist's
      Point of View.
AB  - BACKGROUND: Treatment of non-malignant portal vein thrombosis (PVT) in patients
      with cirrhosis has been neglected in the past because of the fear of bleeding
      complications when using anticoagulation and due to the technical difficulties
      associated with the implantation of the transjugular intrahepatic portosystemic
      shunt (TIPS). However, PVT has a negative impact on outcome and compromises liver
      transplantation, warranting treatment by using anticoagulation and TIPS. METHODS:
      This review considers studies on the treatment of PVT in cirrhosis published in
      the last 10 years. Unfortunately, many of these studies are limited by their
      retrospective design and a small sample size. RESULTS: Anticoagulation using low
      molecular-weight heparin (LMWH) or vitamin K antagonists is effective in the
      treatment of patients with limited and recent PVT, resulting in a recanalization
      in up to 50% of the patients. TIPS (plus local measures) results in a
      recanalization of up to 100% and reduces the rebleeding rate considerably in
      patients with recent or chronic PVT. CONCLUSION: Based on the presently limited
      knowledge, a therapy algorithm is suggested favouring the TIPS as a first-line
      treatment for PVT in patients with symptomatic portal hypertension. Patients with
      thus far asymptomatic portal hypertension may first receive anticoagulation,
      preferably using LMWH. If these patients have a condition where anticoagulation
      is not promising (complete, extended, chronic PVT) or ineffective, or if they are
      candidates for liver transplantation, the TIPS may be implanted without delay.

PMID- 26288608
TI  - Clinical Management of Chronic Portal/Mesenteric Vein Thrombosis: The Surgeon's
      Point of View.
AB  - BACKGROUND: Bleeding from esophageal varices is a life-threatening complication
      of chronic portal hypertension (PH), occuring in 15% of patients with a mortality
      rate between 20 and 35%. METHODS: Based on a literature review and personal
      experience in the therapy of PH, we recommend a therapy strategy for the
      secondary prophylaxis of variceal bleeding in PH. RESULTS: The main causes for PH
      in western countries are alcoholic/viral liver cirrhosis and extrahepatic
      portal/mesenteric vein occlusion, mainly caused by myeloproliferative neoplasms
      or hypercoagulability syndromes. The primary therapy is medical; however, when
      recurrent bleeding occurs, a definitive therapy is required. In the case of
      parenchymal decompensation, liver transplantation is the causal therapy, but in
      case of good hepatic reserve or without underlying liver disease, a portal
      decompressive therapy is necessary. Transjugular intrahepatic portosystemic shunt
      has achieved a widespread acceptance, although evidence is comparable with or
      better for surgical shunting procedures in patients with good liver function. The
      type of surgical shunt should be chosen depending on the patent veins of the
      portovenous system and the personal expertise. CONCLUSION: The therapy decision
      should be based on liver function, morphology of the portovenous system, and
      imminent liver transplantation and should be made by an interdisciplinary team of
      gastroenterologists, interventional radiologists, and visceral surgeons.

PMID- 26288609
TI  - Transanal Tube as a Means of Prevention of Anastomotic Leakage after Rectal
      Cancer Surgery.
AB  - BACKGROUND: Anastomotic leaks after low anterior resection for rectal cancer
      remain the most feared complication. The aim of our study was to investigate
      whether the use of a transanal tube could reduce the leakage rate after this
      surgical procedure. METHODS: This is a retrospective analysis of a single
      institution experience. The study includes 66 patients who underwent low anterior
      resection for rectal cancer without stoma creation between January 2008 and June
      2013. Patients were divided into two groups, i.e. those with a transanal drainage
      tube (TT; n = 9) and those without tube (NTT; n = 57), and evaluated for
      clinically evident anastomotic leakage and postoperative complications. RESULTS:
      The postoperative anastomotic leakage appeared in 5 patients (9%) in the NTT
      group while no single case was observed within the TT group. Despite the
      disadvantageous background in the TT group (a transanal stent was used in the
      most high-risk patients), these patients had no postoperative complications. In
      the NTT group, 23% had some kind of postoperative complications, and 5% died. The
      difference between the two groups is not significant. CONCLUSIONS: Our study
      showed that the use of a transanal tube in low anterior resection for rectal
      cancer could potentially be a simple and effective method of reducing anastomotic
      leakage. In order to prove our observations, larger prospective randomized
      studies should be performed.

PMID- 26288610
TI  - Endoscopic Removal of Pedunculated Leiomyoma of the Sigmoid Colon.
AB  - BACKGROUND: The large bowel is a rare site for leiomyomas. Furthermore, a colonic
      pedunculated leiomyoma is very rare. Complete endoscopic removal of a colonic
      leiomyoma can be problematic because of its submucosal origin. CASE REPORT: We
      report a colonic pedunculated leiomyoma that was removed by endoscopic
      polypectomy without complications. A 74-year-old man was referred to our hospital
      because of constipation. Colonoscopy demonstrated a 1-cm pedunculated polyp that
      was connected to a minute stalk within the sigmoid colon. It was removed by snare
      polypectomy. Histopathological examination demonstrated normal mucosa overlying a
      well-circumscribed proliferation of eosinophilic spindle cells arising in
      association with the muscularis mucosae. Immunohistological findings were
      positive for desmin and smooth muscle actin. The polyp was diagnosed as a
      leiomyoma. More than 9 months later, the patient remains well, with no further
      symptoms. CONCLUSION: For small, pedunculated leiomyomas, endoscopic snare
      polypectomy is thought to be a useful approach for both treatment and diagnosis.

PMID- 26288612
TI  - Natural History and Management of Intraductal Papillary Mucinous Neoplasms:
      Current Evidence.
AB  - BACKGROUND: With the use of modern cross-sectional abdominal imaging modalities,
      an increasing number of cystic pancreatic lesions are identified incidentally.
      Although there is no pathological diagnosis available in most cases, it is
      believed that the majority of these lesions display small branch-duct intraductal
      papillary mucinous neoplasms (BD-IPMNs) of the pancreas. Even though a number of
      large clinical series have been published, many uncertainties remain with regard
      to this entity of mucinous cystic neoplasms. METHODS: Systematic literature
      review. RESULTS: Main-duct (MD) and mixed-type IPMNs harbor a high risk of
      malignant transformation. It is conceivable that most IPMNs with involvement of
      the main duct tend to progress to invasive carcinoma over time. Thus, formal
      oncologic resection is the treatment of choice in surgically fit patients. In
      contrast, the data regarding BD-IPMN remain equivocal, resulting in conflicting
      concepts. To date, it is not clear whether and which BD-IPMNs progress to
      carcinoma and how long this progression takes. CONCLUSION: While patients with MD
      IPMNs should undergo surgical resection if comorbidities and life expectancy
      permit this, the management of small BD-IPMNs remains controversial. Population
      based studies with long-term follow-up are needed to define which cohort of
      patients can be observed safely without immediate resection.

PMID- 26288611
TI  - Management of Incidental Pancreatic Cystic Lesions.
AB  - BACKGROUND: Pancreatic cystic lesions (PCL) are common. They are increasingly
      detected as an incidental finding of transabdominal ultrasound or cross-sectional
      imaging. In contrast to other parenchymal organs, dysontogenetic pancreatic cysts
      are extremely rare. In symptomatic patients the most frequent PCL are acute and
      chronic pseudocysts. The majority of incidental cystic lesions, however, are
      neoplasias which have different risks of malignancy. METHODS: PubMed was searched
      for studies, reviews, meta-analyses, and guidelines using the following key
      words: ('pancreatic cystic lesions' OR 'cystic pancreatic lesions' OR
      'intraductal papillary mucinous neoplasia' OR 'mucinous cystic neoplasia' OR
      'pancreatic cyst' OR 'pancreatic pseudocyst') AND (management OR treatment OR
      outcome OR prognosis OR diagnosis OR imaging OR 'endoscopic ultrasound' EUS-FNA
      OR EUS OR 'endoscopic ultrasonography' OR CT OR MRI). Retrieved papers were
      reviewed with regard to the diagnostic and therapeutic management of incidental
      PCL. RESULTS: In addition to clinical criteria, transabdominal ultrasonography
      including contrast-enhanced ultrasonography, cross-sectional radiological
      imaging, and endoscopic ultrasound (EUS) are used for diagnostic characterization
      and risk assessment. EUS plays an outstanding role in differential diagnosis and
      prognostic characterization of incidental PCL. In a single examination it is
      possible to perform high-resolution morphological description, perfusion imaging,
      as well as fine-needle aspiration of cyst content, cyst wall, and solid
      components. An international consensus guideline has defined worrisome and high
      risk criteria for the risk assessment of mucinous pancreatic cysts, which are
      mainly based on the results of EUS and cross-sectional imaging. Nevertheless,
      despite diagnostic progress and guideline recommendations, differential diagnosis
      and management decisions remain difficult. This review will discuss problems in
      and approaches to the diagnosis of incidental PCL. CONCLUSION: An evidence-based
      algorithm for the diagnosis of incidental PCL is proposed.

PMID- 26288613
TI  - Cyst Features and Risk of Malignancy in Intraductal Papillary Mucinous Neoplasms
      of the Pancreas: Imaging and Pathology.
AB  - BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) display diverse
      macroscopic, histological, and immunohistochemical characteristics with typical
      morphological appearance in magnetic resonance imaging. Depending on those, IPMNs
      may show progression into invasive carcinomas with variable frequency. Overall,
      IPMN-associated invasive carcinomas are found in about 30% of all IPMNs,
      revealing phenotpyes comparable with conventional ductal adenocarcinomas or
      mucinous (colloid) carcinomas of the pancreas. In Sendai-negative side-branch
      IPMNs, however, the annual risk of the development of invasive cancer is 2%;
      thus, risk stratification with regard to imaging and preoperative biomarkers and
      cytology is mandatory. METHODS AND RESULTS: The present study addresses the
      radiological and interventional preoperative measures including histological
      features to determine the risk of malignancy and the prognosis of IPMNs.
      CONCLUSION: While preoperative imaging largely relies on the detection of
      macroscopic features of IPMNs, which are associated with a divergent risk of
      malignant behavior, in resected specimens the determination of the grade of
      dysplasia and the detection of an invasive component are the most important
      features to estimate the prognosis of IPMNs.

PMID- 26288614
TI  - Main- and Branch-Duct Intraductal Papillary Mucinous Neoplasms: Extent of
      Surgical Resection.
AB  - BACKGROUND: Surgical treatment of intraductal papillary mucinous neoplasms (IPMN)
      requires a differentiated approach regarding indications and extent of resection.
      METHODS: The review summarizes the current literature on indication, timing, and
      surgical procedures in IPMN. RESULTS: The most important differentiation has to
      be made between main-duct and branch-duct IPMN as well as mixed-type lesions that
      biologically mimic main-duct types. In main-duct and mixed-type IPMN, the
      resection should be indicated by the time of the diagnosis - in accordance with
      the international consensus guidelines - and should follow oncological
      principles. Depending on IPMN localization, this implies partial
      pancreatoduodenectomy, distal pancreatectomy, or total pancreatectomy and
      includes the corresponding types of lymphadenectomy. Furthermore, branch-duct
      IPMN > 3 cm or bearing high-risk features (mural nodules in magnetic resonance
      imaging, computed tomography, or endoscopic ultrasound imaging; symptomatic
      lesions; elevated tumor markers) are similarly treated. As the risk for
      malignancy in smaller branch-duct IPMN is lower, the decision for surgical
      treatment is often individually made - despite the updated 2012 guidelines. In
      these lesions, limited surgical approaches, including enucleation and central
      pancreatectomy, are possible. CONCLUSION: Timely and radical resection of IPMN
      offers the unique opportunity to prevent pancreatic cancer, and even in malignant
      IPMN surgery can offer a curative approach with excellent long-term outcome in
      early stages. A structured imaging follow-up should be considered to recognize
      IPMN recurrence and metachronous pancreatic cancer as well as gastrointestinal
      neoplasias by endoscopic surveillance.

PMID- 26288615
TI  - Intraductal Papillary Mucinous Adenocarcinoma of the Pancreas: Clinical Outcomes,
      Prognostic Factors, and the Role of Adjuvant Therapy.
AB  - BACKGROUND: Intraductal papillary mucinous adenocarcinoma (IPMCs) occur more
      frequently in main-duct intraductal papillary mucinous neoplasms. METHODS: Review
      of the literature. RESULTS: The prognosis of IPMCs depends on its
      histopathological subtype: colloid IPMCs have superior survival rates mainly
      secondary to more favorable pathological features, whereas tubular IPMCs have
      survival outcomes similar to that of conventional pancreatic adenocarcinomas. The
      epithelial background plays an equally important role in defining the biology of
      IPMCs: gastric IPMC subtypes demonstrate an overall worse survival outcome when
      compared to intestinal, pancreatobiliary, and oncocytic subtypes. Lymph node
      involvement is one of the strongest predictors of survival in IPMC, with a
      decreasing overall survival as the lymph node ratio increases. There is little
      evidence to support adjuvant chemoradiation in patients with IPMC. CONCLUSION:
      Our current understanding of IPMC biology based on histopathological and
      epithelial background subtypes as well as clinicopathological predictors should
      influence patient counseling and selection for adjuvant therapy.

PMID- 26288616
TI  - Giant Filiform Polyposis not Associated with Inflammatory Bowel Disease: A Case
      Report.
AB  - BACKGROUND: Filiform polyposis (FP) is an uncommon cause of non-neoplastic and
      non-syndromic polyposis. Several hypotheses concerning its pathogenesis have been
      published. FP is most frequently associated with a post-inflammatory reparative
      process; indeed, the most frequent association is with inflammatory bowel disease
      (IBD). FP is characterized by one to hundreds of uniform, slender, arborizing,
      vermiform projections of the large bowel mucosa and submucosa lined by normal or
      inflamed colonic mucosa. The most common sites for these polyps are the
      transverse and descending colon. CASE REPORT: In this report we present a case of
      giant FP associated with locally invasive adenocarcinoma of the right colon in a
      73-year-old man with no past medical history of IBD. CONCLUSION: Few of these
      cases have been reported in the literature, and out of the approximately 20 of
      such case reports only one other was associated with colorectal adenocarcinoma.

PMID- 26288617
TI  - Interforaminal hemorrhage during anterior mandibular implant placement: An
      overview.
AB  - Implant surgery in mandibular anterior region may turn from an easy minor surgery
      into a complicated one for the surgeon, due to inadequate knowledge of the
      anatomy of the surgical area and/or ignorance toward the required surgical
      protocol. Hence, the purpose of this article is to present an overview on the:
      (a) Incidence of massive bleeding and its consequences after implant placement in
      mandibular anterior region. (b) Its etiology, the precautionary measures to be
      taken to avoid such an incidence in clinical practice and management of such a
      hemorrhage if at all happens. An inclusion criterion for selection of article was
      defined, and an electronic Medline search through different database using
      different keywords and manual search in journals and books was executed. Relevant
      articles were selected based upon inclusion criteria to form the valid protocols
      for implant surgery in the anterior mandible. Further, from the selected
      articles, 21 articles describing case reports were summarized separately in a
      table to alert the dental surgeons about the morbidity they could come across
      while operating in this region. If all the required adequate measures for
      diagnosis and treatment planning are taken and appropriate surgical protocol is
      followed, mandibular anterior region is no doubt a preferable area for implant
      placement. 

PMID- 26288618
TI  - Effect of the processing cycle on dimensional changes of heat-polymerized denture
      base resins.
AB  - BACKGROUND: The second processing cycle for adding the artificial teeth to heat
      polymerized acrylic resin denture bases may result in dimensional changes of the
      denture bases. The aim of this study was to evaluate the dimensional changes of
      the heat-polymerized acrylic resin denture bases with one and two-cycle
      processing methods. MATERIALS AND METHODS: A metal edentulous maxillary arch was
      used for making 40 stone casts. Maxillary complete dentures were made with heat
      polymerized acrylic resins (Meliodent and Acropars) with one and two stage
      processing methods (n = 10 for each group). Linear dimensional changes in
      anteroposterior and mediolateral distances and vertical changes in the first
      molar region were measured following each processing cycle, using a digital
      caliper. Mean percentage of the dimensional changes were subjected to two-way
      analysis of variance and Tukey honest significant difference tests (alpha =
      0.05). RESULTS: Postpolymerization contraction occurred in both anteroposterior
      and mediolateral directions in all studied groups; however, the vertical
      dimension was increased. Acropars acrylic resin showed the highest dimensional
      changes and the second processing cycle significantly affected the measured
      distances (P < 0.05). Meliodent acrylic resin was not significantly influenced by
      the processing method. CONCLUSION: Reheating of the acrylic resin denture bases
      for the addition of denture teeth result in linear dimensional changes, which can
      be clinically significant based on the acrylic resin used.

PMID- 26288619
TI  - The expression of retinoblastoma tumor suppressor protein in oral cancers and
      precancers: A clinicopathological study.
AB  - BACKGROUND: The role of retinoblastoma (Rb) protein in cell cycle regulation
      prompted us to take up this study with the aim of assessing its role in the
      progression of oral cancer and to correlate with various clinicopathological
      parameters, including habits such as smoking, Paan chewing, and alcoholism.
      MATERIALS AND METHODS: This observational study included surgical specimens from
      10 apparently normal oral mucosa, 14 oral reactive lesions (ORL), 29 precancerous
      lesions and 43 oral cancers. The expression of Rb protein in tissue samples were
      evaluated by immunohistochemistry and correlated with clinicopathological data.
      The percentage and mean expression of Rb protein were statistically analyzed
      using Student's t-test and P < 0.05 was considered as statistically significant
      difference. RESULTS: The expression of Rb protein was found to increase from
      normal, ORL, precancerous lesions to cancers. A consistently high expression of
      Rb protein was seen in oral cancers, with an increase in well-differentiated and
      moderately differentiated tumors. Patients with combined habits of Paan chewing,
      smoking, and alcohol consumption had a higher expression compared with those
      without habits. CONCLUSION: Within the limitations of this study, it seems that
      overexpression of Rb protein noted in oral cancer, with an increase in well and
      moderately differentiated tumors suggest a possible role of Rb in
      differentiation. The high expression of Rb in patients with combined habits of
      Paan chewing, smoking and alcohol consumption indicates that Rb pathway may be
      altered in habit-related oral malignancies.

PMID- 26288620
TI  - Accuracy of different impression materials in parallel and nonparallel implants.
AB  - BACKGROUND: A precise impression is mandatory to obtain passive fit in implant
      supported prostheses. The aim of this study was to compare the accuracy of three
      impression materials in both parallel and nonparallel implant positions.
      MATERIALS AND METHODS: In this experimental study, two partial dentate maxillary
      acrylic models with four implant analogues in canines and lateral incisors areas
      were used. One model was simulating the parallel condition and the other
      nonparallel one, in which implants were tilted 30 degrees  bucally and 20 degrees
      in either mesial or distal directions. Thirty stone casts were made from each
      model using polyether (Impregum), additional silicone (Monopren) and vinyl
      siloxanether (Identium), with open tray technique. The distortion values in three
      dimensions (X, Y and Z-axis) were measured by coordinate measuring machine. Two
      way analysis of variance (ANOVA), one-way ANOVA and Tukey tests were used for
      data analysis (alpha = 0.05). RESULTS: Under parallel condition, all the
      materials showed comparable, accurate casts (P = 0.74). In the presence of
      angulated implants, while Monopren showed more accurate results compared to
      Impregum (P = 0.01), Identium yielded almost similar results to those produced by
      Impregum (P = 0.27) and Monopren (P = 0.26). CONCLUSION: Within the limitations
      of this study, in parallel conditions, the type of impression material cannot
      affect the accuracy of the implant impressions; however, in nonparallel
      conditions, polyvinyl siloxane is shown to be a better choice, followed by vinyl
      siloxanether and polyether respectively.

PMID- 26288621
TI  - Synergic phototoxic effect of visible light or Gallium-Arsenide laser in the
      presence of different photo-sensitizers on Porphyromonas gingivalis and
      Fusobacterium nucleatum.
AB  - BACKGROUND: According to the development of resistant strains of pathogenic
      bacteria following treatment with antimicrobial chemotherapeutic agents,
      alternative approaches such as lethal photosensitization are being used. The aim
      of this study was to evaluate the effect of visible light and laser beam
      radiation in conjugation with three different photosensitizers on the survival of
      two main periodontopathogenic bacteria including Porphyromonas gingivalis and
      Fusobacterium nucleatum in different exposure periods. MATERIALS AND METHODS: In
      this in vitro prospective study, strains of P. gingivalis and F. nucleatum. were
      exposed to visible light at wavelengths of 440 nm and diode laser light, Gallium
      Arsenide, at wavelength of 830 nm in the presence of a photosensitizer
      (erythrosine, curcuma, or hydrogen peroxide). They were exposed 1-5 min to each
      light. Each experiment was repeated 3 times for each strain of bacteria. Data
      were analyzed by two-ways ANOVA and least significant difference post-hoc tests.
      P < 0.05 was considered as significant. After 4 days the colonies were counted.
      RESULTS: Viability of P. gingivalis was reduced 10% and 20% subsequent to
      exposure to visible light and diode laser, respectively. The values were 65% and
      75% for F. nucleatum in a period of 5-min, respectively. Exposure to visible
      light or laser beam in conjugation with the photosensitizers suspension caused
      significant reduction in the number of P. gingivalis in duration of 5-min,
      suggesting a synergic phototoxic effect. However, the survival rate of F.
      nucleatum following the exposure to laser with hydrogen peroxide, erythrosine and
      rhizome of Curcuma longa (curcumin) after 5-min was 10%, 20% and 90%
      respectively. CONCLUSION: Within the limitations of this study, the synergic
      phototoxic effect of visible light in combination with each of the
      photosensitizers on P. gingivalis and F. nucleatum. However, the synergic
      phototoxic effect of laser exposure and hydrogen peroxide and curcumin as
      photosensitizers on F. nucleatum was not shown.

PMID- 26288623
TI  - Effect of different cavity conditioners on microleakage of glass ionomer cement
      with a high viscosity in primary teeth.
AB  - BACKGROUND: Glass ionomer cement is a common material used in pediatric
      dentistry. The aim of this study was to evaluate the microleakage of high
      viscosity glass ionomer restorations in deciduous teeth after conditioning with
      four different conditioners. MATERIALS AND METHODS: Fifty intact primary canines
      were collected. Standard Class V cavities (2 mm * 1.5 mm * 3 mm) were prepared by
      one operator on all buccal tooth surfaces, including both enamel and dentin. The
      samples were divided into five groups with different conditioners (no
      conditioner, 20% acrylic acid, 35% phosphoric acid, 12% citric acid, and 17%
      ethylenediaminetetraacetic acid [EDTA]). Two-way - ANOVA, Kruskal-Wallis and Mann
      Whitney tests were used to compare the means of microleakage between the five
      groups. The significance level was set at P < 0.05. RESULTS: There was no
      significant difference between the means of microleakage in incisal (enamel) and
      gingival (dentin) margins (P = 0.34). Furthermore, there was no significant
      difference between the means of microleakage in enamel and dentin margins (P =
      0.4). There was a significant difference between the means of microleakage in
      different groups (P = 0.03). CONCLUSION: Within the limitations of this study, it
      is suggested that 20% acrylic acid and 17% EDTA be used for cavity conditioning
      which can result in better chemical and micromechanical adhesion.

PMID- 26288622
TI  - Biofilm forming capacity of Enterococcus faecalis on Gutta-percha points treated
      with four disinfectants using confocal scanning laser microscope: An in vitro
      study.
AB  - BACKGROUND: The aim of this study was to evaluate and compare the in vitro
      biofilm forming capacity of Enterococcus faecalis on Gutta-percha points
      disinfected with four disinfectants. MATERIALS AND METHODS: A total of 50 Gutta
      percha points used in this study were divided into four test groups based on
      disinfectant (5.25% sodium hypochlorite, 2% chlorhexidine gluconate, 20% neem,
      13% benzalkonium chloride [BAK]), and one control group. The Gutta-percha points
      were initially treated with corresponding disinfectants followed by anaerobic
      incubation in Brain Heart Infusion broth suspended with human serum and E.
      faecalis strain for 14 days. After incubation, these Gutta-percha points were
      stained with Acridine Orange (Sigma - Aldrich Co., St. Louis, MO, USA) and 0.5 mm
      thick cross section samples were prepared. The biofilm thickness of E. faecalis
      was analyzed quantitatively using a confocal scanning laser microscope. Results
      statistically analyzed using analysis of variance. P < 0.05 was considered to be
      significant. RESULTS: Confocal scanning laser microscope showed reduced amount of
      E. faecalis biofilm on Gutta-percha points treated with BAK and sodium
      hypochlorite. Post-hoc (least square differences) test revealed that there is no
      statistically significant difference between BAK and sodium hypochlorite groups
      (P > 0.05). CONCLUSION: This study illustrates that the Gutta-percha points
      disinfected with sodium hypochlorite and BAK showed minimal biofilm growth on its
      surface.

PMID- 26288624
TI  - Expression of Bcl-2 and epithelial growth factor receptor proteins in
      keratocystic odontogenic tumor in comparison with dentigerous cyst and
      ameloblastoma.
AB  - BACKGROUND: Keratocystic odontogenic tumor (KCOT) is a developmental odontogenic
      cyst on which various investigations have been focused due to its biological
      activities, high tendency to recur and different growth mechanisms in comparison
      with other cystic lesions. Previous studies have shown different biological and
      proliferative activities for the lining epithelium of KCOT. The aim of this study
      was immunohistochemical evaluation of Bcl-2 and epidermal growth factor receptor
      (EGFR) expression in KCOT compared with dentigerous cyst and ameloblastoma.
      MATERIALS AND METHODS: Formalin-fixed and paraffin-embedded tissue sections of 16
      cases of KCOT, 16 cases of dentigerous cyst and 16 cases of ameloblastoma were
      immunohistochemically analyzed to determine Bcl-2 and EGFR proteins' expression.
      Biotin-Stereotavidin method was used. It was observed by two oral pathologists
      separately, and the data were analyzed by Mann-Whitney and Kruskul-Wallis. P <
      0.05 was considered as significant. RESULTS: Regardless of staining intensity,
      all cases of ameloblastoma and KCOT except dentigerous cases were positively
      stained for Bcl-2. Expression of Bcl-2 was higher in the peripheral layer of
      ameloblastoma and basal layer of KCOT. Furthermore, all cases of ameloblastoma
      and dentigerous cysts except KCOT samples were positively stained for EGFR.
      Expression of EGFR was higher in the peripheral layer of ameloblastoma and basal
      layer of dentigerous cysts. CONCLUSION: According to the expression of - Bcl-2 in
      ameloblastoma and KCOT, and no expression of EGFR in KCOT, it can be concluded
      that the biological activity and growth mechanisms of KCOT are different compared
      with other cystic lesions. However, the aggressive potential of KCOT is not as
      severe as that of a neoplasm such as ameloblastoma.

PMID- 26288625
TI  - Evaluation of the effects of three different mouthwashes on the force decay of
      orthodontic chains.
AB  - BACKGROUND: Elastomeric chains are commonly used in orthodontics. Force decay in
      these materials poses clinical problems. The aim of this study was to evaluate
      the effects of three different mouthwashes on the force decay of orthodontic
      chains. MATERIALS AND METHODS: In this experimental study, elastomeric chains
      with two different configurations were divided into eight groups (two control and
      six test groups). After 10 s of prestretching up to 100% of their initial length,
      the chains were stretched for 25 mm on jig pins and then immersed in artificial
      saliva, persica, chlorhexidine 0.2% and sodium fluoride 0.05% mouthwashes. Ten
      cycles of thermocycling between 5 degrees C and 55 degrees C were conducted daily
      during the test period. In order to reach a 200-g initial force, seven loop
      closed chains, and five-loop short chains were selected. Forces were recorded by
      digital force gauge (Lutron) at initial, 24 h, 1, 2, 3 and 4 weeks for all
      groups. The amount of force loss was compared among different mouthwashes and
      times using one-way analysis of variance (post-hoc, Tukey, alpha = 0.05).
      RESULTS: About 20% of the force decay occurred during the first 24 h, but after
      that and up to the 4(th) week the rate of force loss was gradual and steady.
      After 4 weeks, persica and chlorhexidine caused the lowest and the highest
      percentage of force loss, respectively. These two mouthwashes showed
      statistically significant differences at all points of time (P < 0.05).
      CONCLUSION: Within the limitations of this study, during the orthodontic
      treatment, persica is preferred to chlorhexidine for oral health control.

PMID- 26288626
TI  - The effect of budesonide on orthodontic induced root resorption.
AB  - BACKGROUND: The aim of this study was to evaluate the hypothesis that budesonide
      increases the susceptibility of teeth to root resorption during the course of
      orthodontic treatment. MATERIALS AND METHODS: A randomized controlled trial
      design (animal study) was employed. Budesonide was administered in test group for
      14 days during which orthodontic force was applied to upper right molar.
      Afterwards, root resorption was measured on mesio-cervical and disto-apical parts
      of the mesial root on transverse histological sections. ANOVA and Bonfferoni
      tests were used. Statistical significance was considered to be P <= 0.05.
      RESULTS: In general, the subgroups in which the force was applied showed
      significantly greater root resorption. Where force was applied there was no
      significant difference, whether budesonide was administered or not. While where
      there was no force, a group who received budesonide showed significantly greater
      root resorption than the other, unless at the coronal level where the difference
      was not significant. CONCLUSION: Within the limitations of this study, it seems
      budesonide could increase root resorption, but in the presence of orthodontic
      force this effect is negligible.

PMID- 26288627
TI  - Effect of tightening torque on the marginal adaptation of cement-retained implant
      supported fixed dental prostheses.
AB  - BACKGROUND: The final position of the abutment changes with the amount of
      tightening torque. This could eventually lead to loss of passivity and marginal
      misfit of prostheses. The aim of this study was to evaluate the effect of three
      different tightening torques on the marginal adaptation of 3-unit cement-retained
      implant-supported fixed dental prostheses (FDPs). MATERIALS AND METHODS: Two
      implants (Straumann) were inserted in an acrylic block so that one of the
      implants was placed vertically and the other at a 15 degrees  vertical angle. A
      straight abutment and a 15 degrees  angulated abutment were connected to the
      vertically and obliquely installed implants, respectively, so that the two
      abutments were parallel. Then, 10 cement-retained FDPs were waxed and cast.
      Abutments were tightened with 10, 20, and 35 Ncm torques, respectively. Following
      each tightening torque, FDPs were luted on respective abutments with temporary
      cement. The marginal adaptation of the retainers was evaluated using
      stereomicroscope. FDPs were then removed from the abutments and were sectioned at
      the connector sites. The retainers were luted again on their respective
      abutments. Luting procedures and marginal adaptation measurement were repeated.
      Data were analyzed by ANOVA and least significant difference tests (alpha =
      0.05). After cutting the FDP connectors, the independent samples t-test was used
      to compare misfit values (alpha = 0.05). RESULTS: Following 10, 20, and 35 Ncm
      tightening torques, the marginal discrepancy of the retainers of FDPs
      significantly increased (P < 0.05). There was no significant difference between
      the marginal discrepancies of these two retainers (P > 0.05). The marginal gap
      values of angulated abutment retainers (ANRs) were significantly higher than
      those of the straight abutment after cutting the connectors (P = 0.026).
      CONCLUSION: Within the limitations of this study, the marginal misfit of cement
      retained FDPs increased continuously when the tightening torque increased. After
      cutting the connectors, the marginal misfit of the ANRs was higher than those of
      the straight abutment retainers.

PMID- 26288628
TI  - Technical quality of root canal therapies performed by novice dental students in
      preclinical practice.
AB  - BACKGROUND: For improving the quality of endodontic performance of practitioners
      in clinical practice, their basic, preclinical performance and knowledge must be
      taken into consideration. This study aimed to radiographically evaluate the
      technical quality of preclinical molar root canal treatments (RCTs) performed by
      undergraduate dental students at a dental school in Iran. Further, the effect of
      using Gates-Glidden (GG) drills on the final quality of RCTs was evaluated.
      MATERIALS AND METHODS: In this retrospective cross-sectional study, 315 roots of
      105 endodontically treated teeth in preclinical practice were evaluated
      radiographically. The analyzed quality parameters included length, taper and
      density of fillings, which were scored as S2 (adequate standard), the S1 (slight
      deviation), or S0 (considerable deviation). For all the parameters, acceptable,
      moderate and poor fillings received total scores of 6, 3-5 and 0-2, respectively.
      There were two groups of students: One group had used only K-files, and the other
      had used K-files along with GG drills. The quality of RCTs between these groups
      was evaluated using the aforementioned scoring protocol. The results were
      analyzed using Chi-square, Mann-Whitney and Fisher's exact tests (alpha = 0.05).
      RESULTS: Under-fillings (P = 0.001) and under-shapings (P = 0.007) occurred
      mostly in mandibular root fillings. A lower density was found in maxillary
      fillings (P < 0.001). No relationship was observed between the technique used
      (irrespective of GG drills usage) and length (P = 0.499) and taper of fillings (P
      = 0.238). The roots instrumented with GG drills had a higher filling density (P =
      0.004). The quality mean score of RCTs was improved when GG drills were used (P =
      0.008). CONCLUSION: The technical quality of preclinical molar RCTs performed by
      undergraduate dental students was considered acceptable in 35.6% of the cases.
      When GG drills were used along with K-files, the technical quality of RCTs was
      enhanced.

PMID- 26288629
TI  - Periodontal changes following molar intrusion with miniscrews.
AB  - BACKGROUND: With the introduction of skeletal anchorage system, recently it is
      possible to successfully intrude molar teeth. On the other hand, there have been
      concerns about periodontal changes associated with intrusion and there are few
      studies on this topic, especially for posterior teeth. MATERIALS AND METHODS: Ten
      female patients were enrolled in this study. Maxillary molar intrusion was
      achieved by inserting two miniscrews and a 17 * 25 titanium molybdenum alloy
      spring. Crestal height changes were evaluated at three intervals including:
      Baseline (T0), end of active treatment (T1) and 6 months after retention (T2).
      Other variables including probing depth, gingival recession, attachment level and
      bleeding on probing were evaluated by clinical measurements in the three above
      mentioned intervals. One-sample Kolmogrov-Smirnov test ascertained the normality
      of the data. For all patients, the changes in tooth position and crestal height
      were evaluated using one-sample t-test. (P < 0.05). RESULTS: Supra-erupted molars
      were successfully intruded a mean of 2.1 +/- 0.9 mm during active treatment (T0
      T1). A mean bone resorption of 0.9 +/- 0.9 mm in mesial crest and 1 +/- 0.8 mm in
      distal crest had occurred in total treatment (T0-T2). A mean of 0.6 +/- 1.4 mm
      bone was deposited on mesial crest during the retention period (T1-T2) following
      tooth relapse. On average, 0.8 +/- 0.4 mm attachment gain was obtained. Gingival
      margin coronalized a mean of 0.8 +/- 0.6 mm throughout the entire treatment.
      Probing depth showed no significant change during treatment. CONCLUSION: Within
      the limitations of this study, these results suggest that not only periodontal
      status was not negatively affected by intrusion, but also there were signs of
      periodontal improvement including attachment gain and shortening of clinical
      crown height.

PMID- 26288630
TI  - Lower lip numbness due to the mandibular canal narrowing after dental
      reimplantation: A case report.
AB  - Mandibular canal is the most important anatomical landmark in the body of
      mandible which always must be considered for implant surgery in posterior
      mandibular region. Damage to vessels and inferior alveolar nerve that passes
      through the mandibular canal can cause problems such as hemorrhage and
      neurosensory disturbances. Damage to the mandibular canal can occur during
      implant surgery. Depending on the severity of injuries, it would result in
      temporary or permanent neurosensory disturbances. We have reported a case that
      mandibular canal narrowing occurred following implant surgery and resulted in
      anesthetic and hypoesthetic areas in the lower lip. Patient had a history of
      implant surgery in the region of teeth numbered 30 and numbered 31. The inserted
      implant failed after 6 years, and reimplantation was done in this area, but due
      to lower lip numbness in the right side, the second implant was removed, and
      another implant was inserted in the region of the tooth numbered 32. After 2
      years, right lower lip numbness was reported again by the patient. Cone beam
      computed tomography images showed canal narrowing in the region of the tooth
      numbered 31 where the second implant was inserted. It seems that the main cause
      for anesthesia and hypoesthesia in this patient is canal narrowing due to damage
      during implant replacement and removal. 

PMID- 26288631
TI  - Phylogenetic and 2D/3D Analysis of HCV 1a NS4A Gene/Protein in Pakistani
      Isolates.
AB  - BACKGROUND: The nonstructural protein NS4A of hepatitis C virus is composed of 54
      amino acids. This small size protein has vital role in many cellular functions.
      The most important reported function is being a cofactor of viral enzymes serine
      protease and helicase. OBJECTIVES: The objective of this study was to analyze the
      phylogenetic variation, its impact in terms of translation and any functional
      change in protein structure at primary 2D/3D structure using computational tools
      from Pakistani patients isolates. MATERIALS AND METHODS: Patient sera infected
      with Hepatitis C virus, genotype 1A, were obtained from Molecular Diagnostics
      lab, CEMB, University of the Punjab Lahore by using BD Vacutainer collection
      tubes (Becton Dickenson). RESULTS: Phylogenetic analysis of the gene revealed
      that Pakistani 1a HCV strains are in the start of third cluster and there is a
      difference between inter Pakistani isolates at primary, secondary and tertiary
      levels. CONCLUSIONS: Mutations were present in the central domain of NS4A (amino
      acids 21 - 34).

PMID- 26288632
TI  - Genotype 4 Hepatitis E Virus Prevalent in Eastern China Shows Diverse Subtypes.
AB  - BACKGROUND: Hepatitis E Virus (HEV), a zoonotic pathogen, uses several species of
      animal as reservoirs. Swine is considered as the major reservoir for HEV
      infection in humans. Genotype 4 HEV is the dominant cause of hepatitis E disease
      in humans in China. OBJECTIVES: Although many researches revealed that genotype 4
      HEV is the main genotype that prevalent in eastern China, few researches have
      done to study the subtype of HEV in this area. Thus, this study aimed to
      investigate the subtype of HEV prevalent in eastern China. MATERIALS AND METHODS:
      A total of 125 anti-HEV IgM positive human serum and 290 swine fecal samples were
      subjected to reverse transcription polymerase chain reaction (RT-PCR) screening
      of HEV RNA. Positive PCR products were sequenced and phylogenetically analyzed.
      RESULTS: From a total of 125 human serum samples, 19.2% (24.125) were positive,
      while 9.66% (28.290) of the 290 swine fecal samples were positive for HEV RNA.
      Phylogenetic analysis based on partial capsid gene showed that the 51 HEV strains
      in the current study all belonged to genotype 4, clustering into 6 different
      subtypes. Our results also revealed that some of HEV isolates prevalent in the
      human and swine populations were classified into the same clusters. CONCLUSIONS:
      Genotype 4 HEV in eastern China shows subtype diversity and some HEV isolates are
      involved in cross-species transmission.

PMID- 26288633
TI  - Comparison of Different Techniques of Ultrasound-Guided Fine Needle Biopsy of
      Liver in a Swine Model.
AB  - BACKGROUND: The quality of liver biopsy specimens obtained with different fine
      needle biopsy (FNB) techniques has not been compared. OBJECTIVES: This study was
      performed to evaluate the diagnostic quality of three different liver FNB biopsy
      techniques. MATERIALS AND METHODS: Two sequential biopsy series were performed on
      piglets. Three biopsy techniques were compared: capillary-FNB, core-FNB (CFNB)
      and vacuum-assisted CFNB (VACFNB) in a swine model. Initially, 30 liver biopsies
      were performed (ten for each technique). The cellularity and quantity of blood in
      specimens were measured and compared. In the second series, 54 additional
      biopsies using CFNB and VACFNB techniques (27 each) in a separate piglet were
      evaluated in the same fashion. RESULTS: In the first series, cellularity and
      blood levels were significantly lower in capillary-FNB compared with CFNB (P <
      0.001 and P = 0.011, respectively). There was no significant difference between
      CFNB and VACFNB in cellularity and blood (P = 0.15 and P = 0.1, respectively). In
      the second series, cellularity was significantly higher in CFNB compared with
      VACFNB (P < 0.001) with no significant difference in blood (P = 0.5).
      CONCLUSIONS: Among these three different FNB techniques, CFNB technique provided
      the greatest cellularity. Capillary-FNB technique was inferior among all with the
      lowest quality of obtained material for cytopathological interpretation.

PMID- 26288634
TI  - Negative Association of Plasma Levels of Vitamin D and miR-378 With Viral Load in
      Patients With Chronic Hepatitis B Infection.
AB  - BACKGROUND: Chronic Hepatitis B (CHB) is accompanied by inflammation of liver
      because of infection with Hepatitis B Virus (HBV). Previous studies revealed an
      inverse association between vitamin D and HBV DNA levels. OBJECTIVES: The current
      study aimed to investigate the levels of 25 (OH) D3 (the steady form of vitamin
      D), miR-378 and HBV DNA in the patients with CHB. PATIENTS AND METHODS: One
      hundred and seventy three patients with HBeAg negative CHB were recruited for the
      study. Plasma levels of HBVDNA and 25 (OH) D3 were quantified. The expression
      level of miR-378 in plasma was measured by a relative quantitative Real Time
      Polymerase Chain Reaction (qRT-PCR) assay. RESULTS: In the pathway regression
      analysis, the plasma level of 25 (OH) D3 showed a significant inverse correlation
      with plasma levels of HBV DNA (-0.198, P = 0.008) and direct correlation with miR
      378 (0.188, P = 0.013). Similarly plasma level of miR-378 had inverse association
      with HBV DNA level (-0.177, P = 0.020). CONCLUSIONS: These results suggest that
      vitamin D could involve in a miRNA- mediated regulatory pathway in control of HBV
      replication. Further studies are recommended to understand the effects of miR-378
      and anti-infective action of vitamin D on Hepatitis B Virus.

PMID- 26288635
TI  - Predictors of Pegylated Interferon Alpha and Ribavirin Efficacy and Long-Term
      Assessment of Relapse in Patients With Chronic Hepatitis C: A One-Center
      Experience From China.
AB  - BACKGROUND: Sustained virological response (SVR) and virological relapse maintain
      pivotal roles in the management of chronic hepatitis C (CHC); however, there is
      little data regarding the long-term outcomes of patients with CHC in China.
      OBJECTIVES: We aimed to investigate the predictive factors of therapeutic effect
      and viral relapse in patients who achieved end-of-treatment response (ETR).
      PATIENTS AND METHODS: We retrospectively analyzed clinical, biochemical and
      virological data of 169 adult patients with CHC from China who were not treated
      with pegylated interferon-alpha (PEG IFN-alpha) and ribavirin, of which 142
      achieved ETR and with a follow-up period ranging from six months to six years.
      Statistical analysis was performed by SPSS 20.0. RESULTS: Of the 169 patients,
      124 (73.4%) achieved SVR and 23 (16.2%) experienced relapses post-therapy in
      cases of ETR patients. We considered sex, age, alanine aminotransferase,
      aspartate transaminase, baseline hepatitis C virus RNA level, HCV genotypes,
      IL28B rs12979860 genotype, rapid virological response (RVR), and early
      virological response (EVR). For antiviral effect in patients with CHC, HCV
      genotypes (2, 3) (chi(2) = 11.285, P = 0.001), IL28B genotype (rs12979860 CC)
      (chi(2) = 16.552, P < 0.001), RVR (chi(2) = 37.339, P < 0.001), and EVR (chi(2) =
      70.265, P < 0.001) were significantly correlated with achieving SVR. For ETR
      patients with long-term follow-up, the relapse rate within six months was
      significantly higher than within other periods during six-year follow-up (chi(2)
      = 7.792, P = 0.005). Relapse was virtually not observed after therapy ceased for
      48 weeks. The IL28B genotype (rs12979860 CT/TT) (OR = 0.102; 95% CI, 0.031-0.339;
      P < 0.001), lower RVR (OR = 0.239; 95% CI, 0.078-0.738; P = 0.013), and EVR (OR =
      0.102; 95% CI, 0.016-0.661; P = 0.017) were independent risk factors for relapse.
      CONCLUSIONS: Our study comprehensively explored the predictive factors of
      therapeutic effect of administered drugs and analyzed viral relapse during a six
      months to six-year follow-up period from China. The SVR may not be the perfect
      endpoint of HCV therapy in Chinese people; we recommend 48 weeks after treatment
      withdrawal as the suitable time point.

PMID- 26288636
TI  - Simultaneous Presentation of Wilson's Disease and Autoimmune Hepatitis; A Case
      Report and Review of Literature.
AB  - INTRODUCTION: Coexistence of Wilson's disease and autoimmune hepatitis has been
      rarely reported in English literature. In this group of patients, there exist
      features of both diseases and laboratory and histopathological studies may be
      misleading. Medical treatment for any of these entities, per se, may result in
      poor response. Therefore, by considering the acute hepatitis resembling Wilson's
      disease and autoimmune hepatitis, simultaneous therapy with immunosuppressive and
      penicillamine may have a superior benefit. CASE PRESENTATION: We present the case
      of a 10-year-old boy with nausea, vomiting, yellowish discoloration of skin and
      sclera, abdominal pain and tea-color urine. Physical examination showed mild
      hepatomegaly and right upper quadrant tenderness. Laboratory and histochemical
      studies and atomic absorption test were done and the results were highly
      suggestive of both Wilson's disease and autoimmune hepatitis, in him.
      CONCLUSIONS: This case study highlights, although rare, the coexistence of
      Wilson's disease and autoimmune hepatitis and the need to maintain a high level
      of awareness of this problem. Therefore, it is reasonable to consider this type
      of hepatitis in rare patients, with dominant features of both diseases at the
      same time.

PMID- 26288637
TI  - Genomic Diversity of Hepatitis B Virus Infection Associated With Fulminant
      Hepatitis B Development.
AB  - CONTEXT: After five decades of Hepatitis B Virus (HBV) vaccine discovery, HBV is
      still a major public health problem. Due to the high genetic diversity of HBV and
      selective pressure of the host immune system, intra-host evolution of this virus
      in different clinical manifestations is a hot topic of research. HBV infection
      causes a range of clinical manifestations from acute to chronic infection,
      cirrhosis and hepatocellular carcinoma. Among all forms of HBV infection
      manifestations, fulminant hepatitis B infection possesses the highest fatality
      rate. Almost 1% of the acutely infected patients develop fulminant hepatitis B,
      in which the mortality rate is around 70%. EVIDENCE ACQUISITION: All published
      papers deposited in Genbank, on the topic of fulminant hepatitis were reviewed
      and their virological aspects were investigated. In this review, we highlight the
      genomic diversity of HBV reported from patients with fulminant HBV infection.
      RESULTS: The most commonly detected diversities affect regulatory motifs of HBV
      in the core and S region, indicating that these alterations may convert the virus
      to an aggressive strain. Moreover, mutations at T-cell and B-cell epitopes
      located in pre-S1 and pre-S2 proteins may lead to an immune evasion of the virus,
      likely favoring a more severe clinical course of infection. Furthermore, point
      and frame shift mutations in the core region increase the viral replication of
      HBV and help virus to evade from immune system and guarantee its persistence.
      CONCLUSIONS: Fulminant hepatitis B is associated with distinct mutational
      patterns of HBV, underlining that genomic diversity of the virus is an important
      factor determining its pathogenicity.

PMID- 26288639
TI  - Impact of Acceptance and Commitment Therapy on Perceived Stress and Special
      Health Self-Efficacy in Seven to Fifteen-Year-Old Children With Diabetes
      Mellitus.
AB  - BACKGROUND: Diabetes Mellitus (DM) imposes restrictions on physical, emotional
      and social functioning of children and adolescents. OBJECTIVES: The aim of this
      study was to determine the impact of acceptance and commitment therapy (ACT) on
      perceived stress and special health self-efficacy in seven to fifteen-year-old
      children with DM. PATIENTS AND METHODS: The present study was a clinical trial
      with a pretest-posttest control group design. The study population included all
      seven to fifteen-year-old patients who had referred to the Diabetes Mellitus
      Association of Tabriz, Iran, of whom 40 participants were selected using
      convenient sampling. They were randomly allocated to two matched groups
      (experimental and control). The experimental group participated in therapy
      sessions, while the control group did not receive any interventions. The research
      instruments were perceived stress and special health self-efficacy scales.
      RESULTS: The multiple analysis of covariance (MANCOVA) results showed that the
      treatment was effective on variables of perceived stress and special health self
      efficacy (P < 0.001). CONCLUSIONS: The ACT is effective for reducing perceived
      stress and increasing special health self-efficacy in children with DM.

PMID- 26288638
TI  - Correlation of Histopathologic Findings of Non-Graft Threatening
      Preservation/Reperfusion Injury in Time-Zero Liver Needle Biopsies With Short
      Term Post-transplantation Laboratory Alterations.
AB  - BACKGROUND: Early post-transplantation alterations in liver tests are caused by a
      variety of etiologies including rejection, biliary or vascular complications, and
      preservation/reperfusion injury (PRI). OBJECTIVES: The aim of this study was to
      show the correlation between histopathologic changes of PRI and the alterations
      in liver tests in the early post-transplantation period. MATERIALS AND METHODS:
      Between April 2013 and August 2014, histopathologic findings of protocol, time
      zero, Tru-Cut, liver needle biopsies were evaluated in 94 cases of cadaveric
      liver transplantation. The histopathologic changes included ballooning
      degeneration, micro- and macro-vesicular steatosis, bilirubinostasis, apoptotic
      cells, bile plugs and neutrophilic infiltration. These histopathologic changes
      were compared with the early (15 days) post-transplantation liver laboratory
      findings. RESULTS: Clinico-pathologic evaluation of all 94 cases was done by
      assessment of PRI findings in time-zero biopsies and possible causes of allograft
      injury were appraised. In 21 patients, a specific cause for allograft injury was
      found including rejection and/or surgical complications. In the remaining 73
      cases, there was no specific cause for allograft injury and histopathologic
      findings of time-zero liver needle biopsies supported PRI. We classified liver
      laboratory tests alterations as: hepatocellular damage (elevation of
      transaminases and lactate dehydrogenase), cholestatic damage (elevation of
      alkaline phosphatase and total bilirubin) and mixed. Hepatocellular and
      cholestatic alterations in liver function tests were associated with the presence
      of marked apoptotic bodies and neutrophilic aggregates in time zero biopsies,
      respectively. On the other hand, macrovesicular steatosis was dominantly
      associated with mixed (hepatocellular and cholestatic) laboratory alterations of
      liver tests. CONCLUSIONS: Any discrepancy between histopathologic changes in time
      zero biopsies and pattern of early liver laboratory alterations may be considered
      as a warning for causes other than PRI.

PMID- 26288640
TI  - Drug Use and High-Risk Sexual Behaviors of Women at a Drop-In Center in
      Mazandaran Province, Iran, 2014.
AB  - BACKGROUND: Female drug users are more likely to transmit human immunodeficiency
      virus (HIV) to their sexual partners. Little is known about HIV, sexually
      transmitted diseases (STDs), cervicitis, and drug abuse among female sex workers
      in Iran. OBJECTIVES: Therefore, this study was conducted at a drop-in center
      (DIC) in Iran to investigate the prevalence of HIV associated risk factors, the
      prevalence of drug use, high-risk sexual behaviors, and the relationship between
      the associated factors in women. PATIENTS AND METHODS: This quantitative cross
      sectional study was conducted on 190 female sex workers (SW) in a DIC in Sari,
      Mazandaran, Northern Iran, in January and February 2014. The study sample was
      selected through census sampling. In the end, 190 female SWs referring to the DIC
      participated in our study. There was no limitation in sampling. The self
      administered questionnaire was completed via an interview. RESULTS: The results
      showed that 39% of the female SWs were less than 30 years old and 64% had
      elementary school education. In addition, 59% of the participants took some type
      of illegal drugs and 1.1% of them were reportedly injecting drug users. Moreover,
      43% of them had substance dependent husbands, and 39% were reportedly regular
      condom users. They had 1 - 10 sexual partners on average per week. The overall
      prevalence of HIV infection was 4%. A significant relationship was found between
      the type of drugs used and factors such as having a substance dependent husband,
      use of condom during the last sexual contact, regular condom use, and the number
      of sexual acts per week. A significant correlation exists between using
      psychiatric drugs and factors like regular condom use, education, cervicitis, and
      the number of sexual conducts per week. CONCLUSIONS: Female sex workers often
      engage in sex for financial reasons and are at high risk of drug abuse, HIV, and
      cervicitis. In addition, the rate of cervicitis among females with high-risk
      sexual behavior is considerable in Mazandaran, Iran. Therefore, the state
      authorities should provide sex workers with health care services and help them
      acquire a good job to support their life.

PMID- 26288641
TI  - Pure Obsessive Compulsive Disorder in Three Generations.
AB  - INTRODUCTION: Obsessive-compulsive disorder (OCD) is a psychiatric disorder,
      which has been shown to affect 2 - 3.5% of people, during their lifetimes.
      Identification of familial more homogenous characteristics of OCD may help to
      define relevant subtypes and increase the power of genetic and neurobiological
      studies of OCD. CASE PRESENTATION: This case report describes an adult woman
      suffering from symptoms of energy loss, insomnia, lack of appetite, and depressed
      mood. The patient history was positive for counting coercion. The patient's
      genogram revealed counting coercion in three generations of her family.
      CONCLUSIONS: This case highlights the issue whether counting can be a distinctive
      feature among inflicted and not inflicted individuals, such as hoarding. Also, it
      is still unclear what is it really transferred; the vulnerability to disease,
      which is transferred among three generations, or the symptoms of counting itself,
      by genes. Further studies are required to answer the debates on this issue.

PMID- 26288642
TI  - Iranian Common Attitude Toward Opium Consumption.
AB  - Iran is suffering from the 2(nd) most severe addiction to opioids in the world.
      While the explanation of this enormous drug problem is refutably related to drug
      trafficking, the drug dilemma also illustrates the chain reaction of the imposed
      war with Iraq in 1980 - 88; the problems of poverty, unemployment, urbanization,
      homelessness, adultery, family crises, divorce, domestic violence, and runaway
      children. Although opium addiction often linked to these factors, drug use is
      common among all social classes. It seems that a positive traditional attitude is
      another reason for widespread raw opium use in this country. A survey in Iranian
      literature reveals that famous Iranian poets, who have a substantial contribution
      on cultural attitude formation of Iranian population, have used the phrase
      "Teriac" (raw opium) as a means of "antidote" a substance that treats every
      disease. It seems that a concrete deduction from the literature has been leaden
      to a positive attitude towards opium consumption in Persian culture. Recent
      research also supports this idea. Many patients use raw opium as a pain killer or
      for treating hyperlipidemia, hypertension, diabetes and other chronic diseases;
      most of them had started the use after developing the disease and the remaining
      had increased the consumption after developing the disease. Regarding this
      superstitious common belief, drug control headquarters should focus on education
      and correction of the faulty unhealthy attitude toward opium consumption. 

PMID- 26288643
TI  - Short-term Dynamic Psychotherapy versus Sertraline in Treatment of Social Phobia.
AB  - BACKGROUND: A few studies on short-term psychodynamic approach have been
      conducted on social phobia. OBJECTIVES: In this study, the effectiveness of short
      term psychodynamic psychotherapy on the treatment of social phobia has been
      compared to the effectiveness of sertraline and waiting list. MATERIALS AND
      METHODS: In this randomized-controlled trial study, 13 male students were treated
      with short-term dynamic psychotherapy (McCullough method) lasting 25 sessions, 11
      students received sertraline for 12 weeks, and 14 students, as the waiting list,
      received no intervention for 8 weeks. Participants completed the Social Phobia
      Inventory (SPIN) as primary efficacy variable 4 times, and were rated with
      Clinical Global Impression scale (CGI) and Global Assessment of Functioning (GAF)
      as secondary efficacy variables. The data were analyzed with analysis of variance
      (ANOVA), analysis of covariance (ANCOVA), general linear model repeated measures
      analysis of variance and Fisher exact test. RESULTS: ANCOVA showed significant
      differences between groups based on SPIN scores (F = 23.51, Sig. = 0.001) and
      Bonferroni test, as post hoc compression, showed means of both short-term dynamic
      therapy and sertraline therapy groups were significantly different from waiting
      list mean (STDP-WL: [Formula: see text] = 15.76, Sig. = 0.001), (MED-WL:
      [Formula: see text] = 15.91, Sig. = 0.001). Mean of SPIN scores was not
      significantly different between short-term dynamic psychotherapy and
      pharmacotherapy groups. In both treatment groups, means of SPIN scores
      significantly decreased in posttest, but not in waiting. These results repeated
      with GAF and CGI scores. CONCLUSIONS: The results indicated that short-term
      dynamic psychotherapy sertraline are effective in decreasing social phobia
      symptoms and were superior to control group.

PMID- 26288644
TI  - Comparing the Efficacy of 8 Weeks Treatment of Cipram(r) and its Generic
      Citalopram in Patients With Mixed Anxiety-Depressive Disorder.
AB  - BACKGROUND: Patients with mixed anxiety-depressive disorder (MADD) suffer both
      anxiety and depression. Antidepressants, especially, selective serotonin reuptake
      inhibitors are among agents of choice for treating this condition. OBJECTIVES:
      This study compared the efficacy of Cipram(r) with its generic, citalopram.
      PATIENTS AND METHODS: Forty adult outpatients (between 18 to 55 years of age)
      with a diagnosis of MADD who met the trial criteria, entered this double-blind,
      randomized study. Subjects were assigned to receive either generic citalopram or
      Cipram(r) for 8 weeks. Hamilton Rating Scale for Depression (HAM-D) and Hamilton
      Rating Scale for Anxiety (HAM-A) were utilized to assess depression and anxiety
      at baseline, weeks 4 and 8 of the study. Statistical analysis was performed using
      SPSS 14.0. RESULTS: Twenty patients received citalopram (mean dosages of 22
      mg/day during the first 4 weeks and 33 mg/day during weeks 4 to 8) and 20
      received Cipram(r) (mean dosages of 22 mg/day during the first 4 weeks and 29
      mg/day during weeks 4 to 8). Both treatments were noted to be effective in
      improving the symptoms of MADD at weeks 4 and 8. The mean differences of HAM-D
      and HAM-A between Citalopram and Cipram(r) groups were significantly different at
      the end of week 4 (HAM-D: P = 0.038, HAM-A: P = 0.025), but not at the end of
      week 8 (HAM-D: P = 0.239, HAM-A: P = 0.204). Both medications were tolerated well
      by the patients. CONCLUSIONS: This study suggests that the efficacy of citalopram
      is similar to that of Cipram(r) in the treatment of MADD after 8 weeks.
      Meanwhile, Cipram(r) may reduce depression and anxiety quicker than its generic,
      citalopram.

PMID- 26288645
TI  - Relationship Between Psychiatric Distress and Criminal History Among Intravenous
      Drug Abusers in Iran.
AB  - BACKGROUND: Sychotropic agents (alcohol, drugs, and illicit substances) have an
      important effect on the occurrence or exacerbation of psychological and
      behavioral derangements such as criminal activity and mental abnormalities.
      OBJECTIVES: The objective was to assess the relationship between psychiatric
      distress and criminal history among abusers of intravenous drugs, including
      heroin, benzodiazepine, codeine, cannabis, opium, and ecstasy. MATERIALS AND
      METHODS: Criminal activity history and psychiatric distress were evaluated among
      intravenous drug abusers in drop-in centers (DIC) (141 subjects) and an
      outpatient service to delivery methadone to the addicts located in Razy Hospital
      (Baghdad, Iraq) (120 subjects). Logistic regression analyses using the SPSS for
      Windows 18.0 were used for analyzing the data. RESULTS: About 86% of the
      intravenous drug abusers had psychiatric distress and 48.2% had criminal activity
      history. DIC addicts group had a better mental well-being compared to the other
      group, but criminal history rate was similar in two groups. In multiple logistic
      regression, addiction to heroin (odds ratio [OR] = 1.9, 95% confidence interval
      [CI]: 1.1 - 4.1), mental disorders (beta = 0.060, P = 0.026), and low level of
      education was highly related with criminal activity (OR = 0.17, 95% CI: 0.03 -
      0.89). CONCLUSIONS: Higher scores in mental well-being questionnaire of DIC
      addicts suggest the positive effects of psychological interventions. There is a
      possibility of the involvement of heroin in occurrence of mental disorders and
      criminal activity. This finding needs further investigations by larger cohort
      studies.

PMID- 26288646
TI  - Comparison of Demographic and Diagnostic Characteristics of Iranian Inpatients
      With Bipolar I Disorder to Western Counterparts.
AB  - BACKGROUND: Patients' characteristics influence the disorders outcome, so it is
      valuable to compare mood disorders and inpatients' attributes in different large
      samples. OBJECTIVES: This study was designed to assess demographic and diagnostic
      characteristics of 3000 Iranian inpatient with bipolar disorders. PATIENTS AND
      METHODS: We collected the information of demographic, clinical, and therapeutic
      characteristics of the patients who were hospitalized in Iran Hospital of
      Psychiatry, a university affiliated hospital in Tehran, during the 5 years from
      2006 to 2011. RESULTS: About 66.1% of the subjects were males and 33.9% were
      females. Iranian patients are characterized by a higher rate of unemployment,
      being more single, having health insurance and lower rate of divorce and
      education compared to the other clinical samples. In the majority of the
      patients, the disorder had begun with manic phase. CONCLUSIONS: Clinical and
      therapeutic features of Iranian patients are different from patients in western
      countries.

PMID- 26288647
TI  - Acceptance and Commitment Therapy, Selective Serotonin Reuptake Inhibitors and
      Their Combination in the Improvement of Obsessive-Compulsive Symptoms and
      Experiential Avoidance in Patients With Obsessive-Compulsive Disorder.
AB  - BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) and exposure with
      response prevention for treatment of obsessive-compulsive disorder (OCD) have
      demonstrated empirical support; however, a substantial number of patients remain
      with clinically significant OCD symptoms after such treatments. OBJECTIVES: The
      aim of this study was to compare the effectiveness of acceptance and commitment
      therapy (ACT), selective serotonin reuptake inhibitors (SSRIs) and combination of
      ACT and SSRIs in the treatment of adults with obsessive-compulsive disorder
      (OCD). PATIENTS AND METHODS: Thirty-two outpatients meeting Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria
      for OCD were randomly assigned to one of the three treatment conditions: ACT,
      SSRIs and combined treatment. The Yale-Brown Obsessive-Compulsive Scale and
      Acceptance and Action Questionnaire were administered at pre-treatment and post
      treatment. Twenty-seven patients completed the study. Data was analyzed using one
      way analysis of variance (ANOVA) and one-way analysis of covariance (ANCOVA),
      clinically significant change (CSC) and complete remission status. RESULTS:
      ANCOVA revealed that patients treated with ACT and combined treatment experienced
      a significantly greater improvement in obsessive-compulsive (OC) symptoms and
      experiential avoidance (EA) at post-treatment compared to those treated with
      SSRIs alone. However, there were no significant differences between ACT and
      combined treatment on OC symptoms and EA. CSC and complete remission status
      results showed that unlike SSRI, ACT and combined treatment led to more
      improvement in OC symptoms. CONCLUSIONS: ACT and combined treatment are more
      effective than SSRIs alone in treating OC symptoms and EA. However, it appears
      that adding SSRIs to ACT does not increase the effectiveness of ACT in the
      treatment of adults with OCD in the short-term.

PMID- 26288648
TI  - Predicting Early Maladaptive Schemas Using Baumrind's Parenting Styles.
AB  - BACKGROUND: Families play an essential role in maintaining children's mental,
      social, and physical health. The family provides the first and the most important
      social context for human development. OBJECTIVES: The present study aimed to
      predict early maladaptive schemas using Baumrind's parenting styles (root
      development). PATIENTS AND METHODS: A total of 357 undergraduate students of
      Islamic Azad University, Urmia Branch, Iran, were selected through random cluster
      sampling during 2013 and 2014. The students were assessed using the Schema
      Questionnaire-Short Form (SQ-SF) and the Baumrind's parenting styles inventories.
      RESULTS: The result of regression analysis showed that Baumrind's parenting
      styles are significant predictors of early maladaptive schemas (P < 0.001).
      CONCLUSIONS: The authoritative parenting style has some features such as showing
      high levels of warmth or encouraging kids to express their own possibly divergent
      opinions. The authoritarian parenting style, however, possesses traits such as
      heartlessness, impassiveness, strictness, and lack of attention to the children's
      developmental needs, which is not acceptable.

PMID- 26288649
TI  - Drug Use and Sex Work Among At-risk Women: A Qualitative Study of Initial
      Factors.
AB  - BACKGROUND: In recent years, there has been an increasing interest in performing
      research on drug use and sex work among at-risk women. Although there is a well
      documented literature of the initial reasons associated with drug use and sex
      work among women, there is, however, a paucity of information in this area in
      Iran. OBJECTIVES: This study aimed to explore the initial reasons associated with
      drug use and sex work in a group of female treatment seekers, who presented
      health-related risk behaviors, in Tehran, Iran. PATIENTS AND METHODS: This
      qualitative study enrolled a total of 65 at-risk women, from five women-specific
      drug clinics, who participated in the study in 2011. Individual in-depth
      interviews were conducted. Focus group interviews were conducted with 10 key
      informants. All interviews were audio-taped and thematically written. The
      recorded data were analyzed using ATLASti qualitative research software version
      10. RESULTS: The median age of the sample was 34 years. In addition, 44.6% of
      subjects were opiate users, and 55.4% were users of opiates and methamphetamine.
      Sex work was the main source of income for almost half of the sample. The most
      frequently reported reasons, associated with initial drug use, were extrinsic
      motivations, including the drug-using family, friends or social networks.
      Intrinsic motivations, including curiosity and individual willingness to use
      drugs, were other initial reasons. The most frequently reported reasons,
      associated with initial sex work, included the need to purchase drugs and
      financial problems. CONCLUSIONS: The study findings demonstrated a number of
      reasons associated with initial drug use and sex work. The role of sex work in
      providing drugs necessitates education and prevention. Special treatment programs
      should be implemented to prevent sex work among at-risk women in Iran.

PMID- 26288650
TI  - Amyloidoma secondary to insulin injection: Cytologic diagnosis and pitfalls.
AB  - Amyloidomas are rare tumors composed of deposits of amyloid protein not
      associated with systemic amyloidosis. They can present as an initial
      manifestation of a systemic disease process or can be a completely localized
      phenomenon. We present a case of amyloidoma associated with insulin injection
      site found incidentally in an 80-year-old male with multiple co-morbidities who
      presented with diverticulitis associated bleeding. A subcutaneous abdominal mass
      was found on physical examination. Imaging revealed a 5 cm * 1.6 cm homogenous
      subcutaneous lesion. A fine-needle aspiration (FNA) and core biopsy were
      performed under ultrasound guidance to reveal amorphous material proven to be
      amyloidosis at insulin injection sites (AIns) type amyloid. The patient had no
      treatment for this lesion and has had his care triaged to his more serious health
      problems. This is the first case of AIns type amyloidoma associated with insulin
      injection site reported in cytology literature. We highlight the cytologic
      findings and diagnostic pitfalls. As the incidence of diabetes is increasing,
      cytopathologists may encounter this lesion more often on FNA. 

PMID- 26288651
TI  - Urine cytology: Pitfall due to a "remnant" lesion.

PMID- 26288652
TI  - Upper tract urinary cytology to detect upper tract urothelial carcinoma: Using
      the Johns Hopkins Hospital template and evaluation of its feasibility.
AB  - INTRODUCTION: Primary upper urinary tract (UT) urothelial carcinoma (UC) is rare.
      UT washing cytology is often used during UT surveillance. The Johns Hopkins
      Hospital template (JHHT) is primarily designed to use on lower tract urine
      cytology and the data on applying JHHT on UT cytology is limited. We herein study
      the value of UT cytology in detecting UTUC using JHHT in a cohort. MATERIALS AND
      METHODS: One hundred UT cytologic specimens were retrieved from our database
      during a 10-year period (2001-2011). For each patient, the cytology specimen with
      the highest degree of abnormality was selected. Histologic sections of these
      cases were also studied. RESULTS: Seventy-six cases of UT cytology had histologic
      follow-up by either serial (>2) endoscopic biopsies or nephroureterectomy or
      ureterectomy. Among them, the cytologic diagnosis of positive or suspicious for
      high-grade UC (HGUC) was made in 15 cases; suspicious for low-grade UC (LGUC) in
      3 cases; atypical urothelial cells (AUCs) of undetermined significance in 19
      cases; and negative in 39 cases. Of the 15 cases with diagnosis of positive for
      HGUC or AUC-HGUC (AUC-H), 10 had histologically confirmed HGUC, 1 had LGUC, and 4
      had benign histology. All 3 cases of cytologically suspicious for LGUC had LGUC
      on concomitant histology. Among the 19 washings with AUCs with unknown
      significance, 7 were LGUC, 1 was HGUC, and 11 were benign on histology. Six of 39
      cases with negative cytology had UC (3 low-grade and 3 high-grade) on histology.
      Combining positive and AUC-H for UC diagnoses, sensitivity, and specificity for
      detecting HGUC were 71.4% and 91.9%, while for LGUC were 21.4% and 100%,
      respectively. CONCLUSIONS: UT washing cytology has high specificity for detecting
      UC, especially HGUC. Using JHHT on UT washing cytology is feasible, but the
      category of LGUC may need modification.

PMID- 26288653
TI  - Deletion of homologs of the SREBP pathway results in hyper-production of
      cellulases in Neurospora crassa and Trichoderma reesei.
AB  - BACKGROUND: The filamentous fungus Neurospora crassa efficiently utilizes plant
      biomass and is a model organism for genetic, molecular and cellular biology
      studies. Here, a set of 567 single-gene deletion strains was assessed for
      cellulolytic activity as compared to the wild-type parental strain. Mutant
      strains included were those carrying a deletion in: (1) genes encoding proteins
      homologous to those implicated in the Saccharomyces cerevisiae secretion
      apparatus; (2) genes that are homologous to those known to differ between the
      Trichoderma reesei hyper-secreting strain RUT-C30 and its ancestral wild-type
      strain; (3) genes encoding proteins identified in the secretome of N. crassa when
      cultured on plant biomass and (4) genes encoding proteins predicted to traverse
      the secretory pathway. RESULTS: The 567 single-gene deletion collection was
      cultured on crystalline cellulose and a comparison of levels of secreted protein
      and cellulase activity relative to the wild-type strain resulted in the
      identification of seven hyper-production and 18 hypo-production strains. Some of
      these deleted genes encoded proteins that are likely to act in transcription,
      protein synthesis and intracellular trafficking, but many encoded fungal-specific
      proteins of undetermined function. Characterization of several mutants
      peripherally linked to protein processing or secretion showed that the hyper- or
      hypo-production phenotypes were primarily a response to cellulose. The altered
      secretome of these strains was not limited to the production of cellulolytic
      enzymes, yet was part of the cellulosic response driven by the cellulase
      transcription factor CLR-2. Mutants implicated the loss of the SREBP pathway,
      which has been found to regulate ergosterol biosynthesis genes in response to
      hypoxic conditions, resulted in a hyper-production phenotype. Deletion of two
      SREBP pathway components in T. reesei also conferred a hyper-production phenotype
      under cellulolytic conditions. CONCLUSIONS: These studies demonstrate the utility
      of screening the publicly available N. crassa single-gene deletion strain
      collection for a particular phenotype. Mutants in a predicted E3 ligase and its
      target SREBP transcription factor played an unanticipated role in protein
      production under cellulolytic conditions. Furthermore, phenotypes similar to
      those observed in N. crassa were seen following the targeted deletion of
      orthologous SREBP pathway loci in T. reesei, a fungal species commonly used in
      industrial enzyme production.

PMID- 26288654
TI  - Microbial community dynamics in replicate anaerobic digesters exposed
      sequentially to increasing organic loading rate, acidosis, and process recovery.
AB  - BACKGROUND: Volatile fatty acid intoxication (acidosis), a common process failure
      recorded in anaerobic reactors, leads to drastic losses in methane production.
      Unfortunately, little is known about the microbial mechanisms underlining
      acidosis and the potential to recover the process. In this study, triplicate
      mesophilic anaerobic reactors of 100 L were exposed to acidosis resulting from an
      excessive feeding with sugar beet pulp and were compared to a steady-state
      reactor. RESULTS: Stable operational conditions at the beginning of the
      experiment initially led to similar microbial populations in the four reactors,
      as revealed by 16S rRNA gene T-RFLP and high-throughput amplicon sequencing.
      Bacteroidetes and Firmicutes were the two dominant phyla, and although they were
      represented by a high number of operational taxonomic units, only a few were
      dominant. Once the environment became deterministic (selective pressure from an
      increased substrate feeding), microbial populations started to diverge between
      the overfed reactors. Interestingly, most of bacteria and archaea showed
      redundant functional adaptation to the changing environmental conditions.
      However, the dominant Bacteroidales were resistant to high volatile fatty acids
      content and low pH. The severe acidosis did not eradicate archaea and a clear
      shift in archaeal populations from acetotrophic to hydrogenotrophic
      methanogenesis occurred in the overfed reactors. After 11 days of severe acidosis
      (pH 5.2 +/- 0.4), the process was quickly recovered (restoration of the biogas
      production with methane content above 50 %) in the overfed reactors, by adjusting
      the pH to around 7 using NaOH and NaHCO3. CONCLUSIONS: In this study we show that
      once the replicate reactors are confronted with sub-optimal conditions, their
      microbial populations start to evolve differentially. Furthermore the alterations
      of commonly used microbial parameters to monitor the process, such as richness,
      evenness and diversity indices were unsuccessful to predict the process failure.
      At the same time, we tentatively propose the replacement of the dominant
      Methanosaeta sp. in this case by Methanoculleus sp., to be a potential warning
      indicator of acidosis.

PMID- 26288655
TI  - IL-17 cytokines in bone healing of diabetic Charcot arthropathy patients: a
      prospective 2 year follow-up study.
AB  - BACKGROUND: Little is currently known of the pathophysiological mechanisms
      triggering Charcot arthropathy and regulating its recovery although foot trauma
      has been proposed as a major initiating factor by activation of proinflammatory
      cytokines leading to increased osteoclastogenic activity and progressive bone
      destruction. Several members of the IL-17 family of proinflammatory cytokines
      have been shown to play a key role in the pathogenesis of inflammatory conditions
      affecting bone and joints but none has previously been studied in Charcot foot
      patients. The aim of this study was to investigate the role of IL-17A, IL-17E and
      IL-17F in patients presenting with Charcot foot. METHODS: Twenty-six consecutive
      Charcot patients were monitored during 2 years by repeated foot radiographs, MRI
      and circulating levels of IL-17A, IL-17E and IL-17F. Analysis of cytokines was
      done by ultra-sensitive chemiluminescence technique and data were analyzed by one
      way repeated measures ANOVA. Neuropathic diabetic patients (n = 20) and healthy
      subjects (n = 20) served as controls. RESULTS: Plasma IL-17A and IL-17E in weight
      bearing Charcot patients at diagnosis were at the level of diabetic controls,
      whereas IL-17F was significantly lower than diabetic controls. A significant
      increase in IL-17A and IL-17E reaching a peak 2-4 months after inclusion and
      start of offloading treatment in Charcot patients was followed by a gradual
      decrease to the level of diabetic controls at 2 years postinclusion. In contrast,
      IL-17F increased gradually from inclusion to a level not significantly different
      from diabetic controls after 2 years. CONCLUSIONS: Charcot patients display a
      significant elevation of all three IL-17 cytokines during the follow-up period
      relative values at diagnosis and values in control patients supporting a role in
      the bone repair and remodeling activity during the recovery phase. The rapid
      increase of IL-17A and IL-17E shortly after initiating off-loading treatment
      could suggest this to be a response to immobilization and stabilization of the
      diseased foot.

PMID- 26288656
TI  - Determinants of footwear difficulties in people with plantar heel pain.
AB  - BACKGROUND: Plantar heel pain is a common foot disorder aggravated by weight
      bearing activity. Despite considerable focus on therapeutic interventions such as
      orthoses, there has been limited investigation of footwear-related issues in
      people with plantar heel pain. The aim of this study was to investigate whether
      people with plantar heel pain experience footwear-related difficulties compared
      to asymptomatic individuals, as well as identifying factors associated with
      footwear comfort, fit and choice. METHODS: The footwear domain of the Foot Health
      Status Questionnaire (FHSQ) was assessed in 192 people with plantar heel pain and
      69 asymptomatic controls. The plantar heel pain group was also assessed on a
      variety of measures including: foot posture, foot strength and flexibility,
      pedobarography and pain level. A univariate analysis of covariance, with age as
      the covariate, was used to compare the heel pain and control groups on the FHSQ
      footwear domain score. A multiple regression model was then constructed to
      investigate factors associated with footwear scores among participants with
      plantar heel pain. RESULTS: When compared to asymptomatic participants, people
      with plantar heel pain reported lower FHSQ footwear domain scores (mean
      difference -24.4; p < 0.001; 95 % CI: -32.0 to -17.0). In the participants with
      heel pain, footwear scores were associated with maximum force beneath the postero
      lateral heel during barefoot walking, toe flexor strength and gender.
      CONCLUSIONS: People with plantar heel pain experience difficulty with footwear
      comfort, fit and choice. Reduced heel loading during barefoot walking, toe flexor
      weakness and female gender are all independently associated with reports of
      footwear difficulties in people with heel pain. Increased focus, in both clinical
      and research settings, is needed to address footwear-related issues in people
      with plantar heel pain.

PMID- 26288657
TI  - Characteristics of the first metatarsophalangeal joint in gout and asymptomatic
      hyperuricaemia: a cross-sectional observational study.
AB  - BACKGROUND: This study aimed to identify patient-reported outcomes and clinician
      assessed characteristics of the first metatarsophalangeal joint (1MTPJ) in people
      with gout and with asymptomatic hyperuricaemia by comparing them to
      normouricaemic controls. METHODS: Twenty four people with gout (without current
      symptoms of acute arthritis), 29 with asymptomatic hyperuricaemia and 34 age- and
      sex-matched controls participated in this cross-sectional observational study.
      Patient-reported outcomes included 1MTPJ pain, foot pain and disability, body
      pain, lower limb function, activity limitation and overall wellbeing. Clinician
      assessed characteristics of the 1MTPJ included range of motion (ROM), plantar-
      and dorsi-flexion force, foot posture, temperature and hallux valgus severity.
      RESULTS: Compared to controls, participants with gout reported greater 1MTPJ pain
      (p = 0.014), greater foot pain and disability (p < 0.001), increased odds of
      having disabling foot pain (odds ratio (OR) 13.4, p < 0.001), decreased lower
      limb function for daily living (p = 0.002) and recreational (p < 0.001)
      activities, increased activity limitation (p = 0.002), reduced overall wellbeing
      (p = 0.034), reduced ROM (p < 0.001), reduced plantarflexion force (p = 0.012),
      increased 1MTPJ plantar (p = 0.004), dorsal (p = 0.003) and medial (p = 0.004)
      temperature and had increased odds of having more severe hallux valgus (OR 0.3 p
      = 0.041). Compared to controls, participants with asymptomatic hyperuricaemia had
      increased odds of having disabling foot pain (OR 4.2, p = 0.013), increased
      activity limitation (p = 0.033), decreased lower limb function for daily living
      (p = 0.026) and recreational (p = 0.010) activities, increased 1MTPJ
      plantarflexion force (p = 0.004) and a more pronated foot type (p = 0.036).
      CONCLUSIONS: People with gout demonstrate 1MTPJ-specific changes indicative of
      subclinical inflammation, even in the absence of acute arthritis. People with
      asymptomatic hyperuricaemia, who exhibit no features or symptoms of gout, also
      report high levels of foot- and lower limb-related pain and disability.

PMID- 26288658
TI  - Interaction of caffeine with the SOS response pathway in Escherichia coli.
AB  - BACKGROUND: Previous studies have highlighted the antimicrobial activity of
      caffeine, both individually and in combination with other compounds. A proposed
      mechanism for caffeine's antimicrobial effects is inhibition of bacterial DNA
      repair pathways. The current study examines the influence of sub-lethal caffeine
      levels on the growth and morphology of SOS response pathway mutants of
      Escherichia coli. METHODS: Growth inhibition after treatment with caffeine and
      methyl methane sulfonate (MMS), a mutagenic agent, was determined for E. coli
      mutants lacking key genes in the SOS response pathway. The persistence of
      caffeine's effects was explored by examining growth and morphology of caffeine
      and MMS-treated bacterial isolates in the absence of selective pressure. RESULTS:
      Caffeine significantly reduced growth of E. coli recA- and uvrA-mutants treated
      with MMS. However, there was no significant difference in growth between umuC
      isolates treated with MMS alone and MMS in combination with caffeine after 48 h
      of incubation. When recA-isolates from each treatment group were grown in
      untreated medium, bacterial isolates that had been exposed to MMS or MMS with
      caffeine showed increased growth relative to controls and caffeine-treated
      isolates. Morphologically, recA-isolates that had been treated with caffeine and
      both caffeine and MMS together had begun to display filamentous growth.
      CONCLUSIONS: Caffeine treatment further reduced growth of recA- and uvrA-mutants
      treated with MMS, despite a non-functional SOS response pathway. However,
      addition of caffeine had very little effect on MMS inhibition of umuC-mutants.
      Thus, growth inhibition of E. coli with caffeine treatment may be driven by
      caffeine interaction with UmuC, but also appears to induce damage by additional
      mechanisms as evidenced by the additive effects of caffeine in recA- and uvrA
      mutants.

PMID- 26288660
TI  - Results of glycated hemoglobin during treatment with insulin analogues dispensed
      in the public health system of Federal District in Brazil.
AB  - BACKGROUND: Diabetes treatment requires specialized multi-professional teams,
      supplies for blood glucose monitoring and training for self-injections of human
      insulin or insulin analogues. The State Health Secretariat of the Federal
      District (SHS-FD) has dispensed insulin analogues by means of clinical validated
      protocols since 2004. However, data on outcomes of follow-up are still unknown.
      OBJECTIVE: To evaluate the results of glycated hemoglobin (HbA1c) among diabetic
      patients treated with insulin analogues. METHODS: It is a retrospective cohort
      study involving data of type 1(DM1) and type 2 diabetes (DM2) patients 18 years
      old and above who were registered to participate at the insulin analogues
      dispense program of the SHS-FD. Evaluation of criteria of insulin treatment
      continuity was based on HbA1c values achieved in the follow-up period: in the
      target, <7 %, patients between 18 and 65 years old; <8 % for those above 65 years
      old; out of target, when values were superior these cut off points for both age
      groups; and minimum 0.5 % reduction of two HbA1c values during follow-up.
      RESULTS: Two hundred and fifteen formularies were analyzed: Type 2 patients (63.7
      %) and female sex were the most prevalent (63.7 %), (p < 0.05). Mean age and SD
      were 41.5 +/- 23.5 years among DM1 and 60.5 +/- 28.5 in those with DM2. HbA1c in
      the target was found in 26 %, 48 % were out of target and 26 % achieved 0.5 %
      minimum reduction in HbA1c value (p < 0.05). The main clinical characteristics
      associated with HbA1c found to be in the target were older age (>65 years), more
      than three medical appointments in the follow-up and lower mean HbA1c in the
      patient selection for inclusion criteria in the dispense program (p < 0.05).
      CONCLUSION: The low number of patients using insulin analogues in the target
      group, considered to be in good control, implies the need to reevaluate both
      level of patients self-care knowledge and glucose monitoring prior their
      inclusion in the insulin analogue dispense program. Reinforcement and training of
      health professional teams in enrollment procedures should be on mandatory basis
      to avoid protocol failure or deviations.

PMID- 26288659
TI  - Comparative analysis of therapeutic efficiency and costs (experience in Bulgaria)
      of oral antidiabetic therapies based on glitazones and gliptins.
AB  - Type 2 diabetes mellitus is a serious, chronic, progressive and widespread
      disease. Metformin is the most commonly prescribed initial therapy, but
      combination with other antidiabetic agents usually becomes necessary due to the
      progression of the disease. Pioglitazone is recommended as a second-line therapy
      because of its strong antihyperglycemic effect and its ability to reduce insulin
      resistance. Treatment with pioglitazone is associated with a significantly lower
      risk of cardiovascular complications and hypoglycemia, while simultaneously
      improving the lipid profile and the symptomatic and histological changes in the
      liver. Gliptins (sitagliptin and vildagliptin) are a new class of oral
      antidiabetic drugs which reduce glycated hemoglobin by a different mechanism.
      Although the efficacy of sitagliptin and vildagliptin is close to that of
      pioglitazone, the lack of long-term safety data and the higher price question
      their predominant use. The objective of this review is to highlight the
      advantages of mono- and combination therapy with pioglitazone in comparison with
      gliptins and to underline the inconsistencies in the medicinal and reimbursement
      policy in Bulgaria. 

PMID- 26288661
TI  - Regulation of hepatic TRB3/Akt interaction induced by physical exercise and its
      effect on the hepatic glucose production in an insulin resistance state.
AB  - To maintain euglycemia in healthy organisms, hepatic glucose production is
      increased during fasting and decreased during the postprandial period. This whole
      process is supported by insulin levels. These responses are associated with the
      insulin signaling pathway and the reduction in the activity of key gluconeogenic
      enzymes, resulting in a decrease of hepatic glucose production. On the other
      hand, defects in the liver insulin signaling pathway might promote inadequate
      suppression of gluconeogenesis, leading to hyperglycemia during fasting and after
      meals. The hepatocyte nuclear factor 4, the transcription cofactor PGC1-alpha,
      and the transcription factor Foxo1 have fundamental roles in regulating
      gluconeogenesis. The loss of insulin action is associated with the production of
      pro-inflammatory biomolecules in obesity conditions. Among the molecular
      mechanisms involved, we emphasize in this review the participation of TRB3
      protein (a mammalian homolog of Drosophila tribbles), which is able to inhibit
      Akt activity and, thereby, maintain Foxo1 activity in the nucleus of hepatocytes,
      inducing hyperglycemia. In contrast, physical exercise has been shown as an
      important tool to reduce insulin resistance in the liver by reducing the
      inflammatory process, including the inhibition of TRB3 and, therefore,
      suppressing gluconeogenesis. The understanding of these new mechanisms by which
      physical exercise regulates glucose homeostasis has critical importance for the
      understanding and prevention of diabetes. 

PMID- 26288662
TI  - Obesity with metabolic abnormality is associated with the presence of carotid
      atherosclerosis in Korean men: a cross-sectional study.
AB  - BACKGROUND: Obesity is a risk factor for cardiovascular disease, but metabolic
      disturbances can also lead to the development of this disease. Therefore, we
      investigated the associations between obesity subtype, considering both body
      weight and metabolic disturbances, and carotid atherosclerosis as a predictor of
      cardiovascular disease in Korean men. METHODS: Data from a total of 980 men were
      analysed in this study. Obesity subtypes were classified as normal weight without
      metabolic syndrome (metabolically healthy normal weight; MHNW), obesity without
      metabolic syndrome (metabolically healthy, but obese; MHO), normal weight with
      metabolic syndrome (metabolically abnormal, but normal weight; MANW) and obesity
      with metabolic syndrome (metabolically abnormal obese; MAO). Carotid intima-media
      thickness (CIMT) and carotid plaque were assessed using a high-resolution B-mode
      ultrasound system. Carotid atherosclerosis was defined as a mean CIMT value >0.9
      mm or the presence of carotid plaque. RESULTS: Mean CIMT in the MAO subtype was
      significantly higher than that in the MHNW control group (0.790 +/- 0.019 vs.
      0.747 +/- 0.013 mm; p < 0.001). The presence of carotid plaque was positively
      associated with MAO subtype [adjusted odds ratio (aOR) 1.49, 95 % confidence
      interval (CI) 1.02-2.16; p = 0.039], but not with MHO or MANW, compared to the
      MHNW control group. The MAO subtype showed a positive association with the
      presence of carotid atherosclerosis (aOR 1.68, 95 % CI 1.17-2.42; p = 0.006).
      CONCLUSIONS: Only the MAO subtype showed a higher CIMT value and positive
      associations with carotid plaque and carotid atherosclerosis, but not with MHO
      and MANW subtypes, compared to the MHNW control. Additional prospective studies
      are needed to evaluate preclinical carotid atherosclerosis according to the
      subtypes of obesity.

PMID- 26288663
TI  - Belimumab in systemic lupus erythematosus: a perspective review.
AB  - Belimumab (Benlysta((r))) is a fully humanized monoclonal antibody that inhibits
      B-lymphocyte stimulator (also known as B cell activating factor of the tumor
      necrosis factor family) and was approved by the US Food and Drug Administration
      and the European Medicines Evaluation Agency for treatment of autoantibody
      positive systemic lupus erythematosus (SLE) in adults. This review discusses the
      key findings of the phase III trials, post hoc analyses, and real-world
      postmarketing use of belimumab in the routine care of SLE patients. It also
      highlights the safety profile of belimumab and gives insight into its potential
      use to treat childhood-onset SLE. It concludes with a discussion of the current
      clinical trials investigating belimumab in specific SLE disease states and a look
      to the future with novel targeted B-cell therapies. 

PMID- 26288665
TI  - More than healthy bones: a review of vitamin D in muscle health.
AB  - Vitamin D has known importance to bone health including calcium and phosphate
      homeostasis and appears to have a role in skeletal muscle health as well. Cases
      of vitamin D deficiency and insufficiency have been associated with poor muscle
      health. While the exact effects and mechanism of action remains controversial,
      current data lean towards insufficient vitamin D playing a role in
      musculoskeletal pain, sarcopenia, myopathy, falls and indirectly via cerebellar
      and cognitive dysfunction. Sophisticated experimental techniques have allowed
      detection of the vitamin D receptor (VDR) on skeletal muscle and cerebellar
      tissue, which if validated in further large studies, could confirm the mechanism
      of vitamin D in these associations. While further study is required, vitamin D
      repletion can have a substantial impact on muscle as well as bone health. 

PMID- 26288664
TI  - B-cell survival factors in autoimmune rheumatic disorders.
AB  - Autoimmune rheumatic disorders have complex etiopathogenetic mechanisms in which
      B cells play a central role. The importance of factors stimulating B cells,
      notably the B-cell activating factor (BAFF) and A proliferation inducing ligand
      (APRIL) axis is now recognized. BAFF and APRIL are cytokines essential for B-cell
      proliferation and survival from the immature stages to the development of plasma
      cells. Their levels are increased in some subsets of patients with autoimmune
      disorders. Several recent biologic drugs have been developed to block this axis,
      namely belimumab [already licensed for systemic lupus erythematosus (SLE)
      treatment], tabalumab, atacicept and blisibimod. Many clinical trials to evaluate
      the safety and efficacy of these drugs in several autoimmune disorders are
      ongoing, or have been completed recently. This review updates the information on
      the use of biologic agents blocking BAFF/APRIL for patients with SLE, rheumatoid
      arthritis, Sjogren's syndrome and myositis. 

PMID- 26288666
TI  - Oral bisphosphonates and colon cancer: an update.
AB  - Bisphosphonates (BPs) are widely used as the main treatment for osteoporosis. In
      vitro and animal studies suggest that use of BPs may have a potential for
      colorectal cancer (CRC) prevention. Safety and efficacy in terms of osteoporosis
      prevention have only been evaluated in randomized controlled trials (RCTs) of
      relatively short duration (3-5 years), with smaller extension studies. The
      evidence for a benefit beyond 5 years is limited and intake of BPs has not shown
      any relationship with CRC in intervention studies. Observational studies and meta
      analysis have shown unchanged or decreased risk of CRC. BPs used for treatment
      and prevention of osteoporosis should not be applied for prevention of CRC in
      clinical practice. 

PMID- 26288667
TI  - Should CT Angiography be a Routine Component of Acute Stroke Imaging?

PMID- 26288668
TI  - Intravenous Thrombolysis for Acute Ischemic Stroke Within 3 Hours Versus Between
      3 and 4.5 Hours of Symptom Onset.
AB  - Data from randomized clinical trials have supported the safety and efficacy of
      intravenous tissue-type plasminogen activator (IV tPA) for acute ischemic stroke
      when administered within 3 hours of symptom onset, and regulatory approvals for
      this indication have been in place for almost 20 years. However, recent clinical
      trials have provided evidence that IV tPA may be safe and effective in selected
      patients up to 4.5 hours after symptom onset, thereby increasing the proportion
      of patients that may be eligible for treatment. Although professional
      organizations in the United States and many regulatory agencies internationally
      have supported this expanded time window for IV tPA, the US Food and Drug
      Administration has declined to approve this expanded indication and so this use
      of IV tPA has remained off-label in the United States. Here we review the current
      evidence for IV tPA in the standard and the expanded time windows and the data on
      current clinical practice in the United States as it relates to IV tPA treatment
      for acute stroke within 3 to 4.5 hours of symptom onset. 

PMID- 26288669
TI  - Absolute and Relative Contraindications to IV rt-PA for Acute Ischemic Stroke.
AB  - Most of the contraindications to the administration of intravenous (IV)
      recombinant tissue plasminogen activator (rtPA) originated as exclusion criteria
      in major stroke trials. These were derived from expert consensus for the National
      Institute of Neurological Disorders and Stroke (NINDS) trial. Despite the fact
      that the safety and efficacy of IV rtPA has been repeatedly confirmed in large
      international observational studies over the past 20 years, most patients with
      acute ischemic stroke disappointingly still do not receive thrombolytic
      treatment. Some of the original exclusion criteria have proven to be
      unnecessarily restrictive in real-world clinical practice. It has been suggested
      that application of relaxed exclusion criteria might increase the IV thrombolysis
      rate up to 20% with comparable outcomes to thrombolysis with more conventional
      criteria. We review the absolute and relative contraindications to IV rtPA for
      acute ischemic stroke, discussing the underlying rationale and evidence
      supporting these exclusion criteria. 

PMID- 26288670
TI  - What is the Role for Intra-Arterial Therapy in Acute Stroke Intervention?
AB  - Intravenous recombinant tissue plasminogen activator continues to be first-line
      therapy for patients with acute ischemic stroke presenting within the appropriate
      time window, but one potential limitation is the low rate of recanalization in
      the setting of large artery occlusions. Intra-arterial (IA) treatment is
      effective for emergency revascularization of proximal intracranial arterial
      occlusions, but proof of benefit has been lacking until recently. Our goal is to
      outline the history of endovascular therapy and review both IA thrombolysis and
      mechanical interventions. In addition, we will discuss the impact of important
      trials such as the Third Interventional Management of Stroke (IMS3) trial, and
      the more recent trials Multicenter Randomized Clinical Trial of Endovascular
      Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN), Endovascular
      Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE),
      Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra
      Arterial (EXTEND-IA), and Solitaire With the Intention for Thrombectomy as
      Primary Endovascular Treatment (SWIFT PRIME) on acute stroke management and the
      implications for the practicing neurohospitalist. 

PMID- 26288672
TI  - Basilar Occlusion Syndromes: An Update.
AB  - Basilar artery occlusions (BAOs) are a subset of posterior circulation strokes.
      Particular issues relevant to BAOs include variable and stuttering symptoms at
      onset resulting in delays in diagnosis, high morbidity and mortality, and
      uncertain best management. Despite better imaging techniques, diagnosis, and
      therefore treatment, is often delayed. We will present the most common signs and
      symptoms of posterior circulation strokes. Data on optimal treatment strategies
      are gathered from multiple case series, registries, and one randomized trial,
      which was stopped early. Possible etiologies of BAOs, acute, and subacute
      treatment strategies and special topics in neuroimaging of the posterior fossa
      are discussed. This review may be helpful to neurohospitalists who are managing
      patients with acute stroke as well as emergency room physicians and neurologists.

PMID- 26288671
TI  - Management of Postthrombolysis Hemorrhagic and Orolingual Angioedema
      Complications.
AB  - Intravenous recombinant tissue plasminogen activator was first approved for the
      treatment of acute ischemic stroke in the United States in 1996. Thrombolytic
      therapy has been proven to be effective in acute ischemic stroke treatment and
      shown to improve long-term functional outcomes. Its use is associated with an
      increased risk of symptomatic intracerebral hemorrhage as well as orolingual
      angioedema. Our goal is to outline the management strategies for these
      postthrombolysis complications. 

PMID- 26288673
TI  - TIA Management: Should TIA Patients be Admitted? Should TIA Patients Get
      Combination Antiplatelet Therapy?
AB  - Transient ischemic attack (TIA) has gained increasing attention over the last 2
      decades with the realization that the condition is common, portends potentially
      serious consequences, and, when identified early, can be evaluated and treated to
      modify future risk. In this review, we examine the issues of whether all TIA
      patients need admission and whether such patients should receive short-term dual
      antiplatelet therapy. Not all patients require admission if evaluation and
      treatment are done promptly. There may be a role for dual antiplatelet therapy,
      but the results of further clinical trials will help provide better clarity on
      which patients are the best candidates for this treatment. 

PMID- 26288675
TI  - In-Hospital Ischemic Stroke.
AB  - Between 2.2% and 17% of all strokes have symptom onset during hospitalization in
      a patient originally admitted for another diagnosis or procedure. These in
      hospital strokes represent a unique population with different risk factors, more
      mimics, and substantially worsened outcomes compared to community-onset strokes.
      The fact that these strokes manifest during the acute care hospitalization, in
      patients with higher rates of thrombolytic contraindications, creates distinct
      challenges for treatment. However, the best evidence suggests benefit to treating
      appropriately selected in-hospital ischemic strokes with thrombolysis. Evidence
      points toward a "quality gap" for in-hospital stroke with longer in-hospital
      delays to evaluation and treatment, lower rates of evaluation for etiology, and
      decreased adherence to consensus quality process measures of care. This quality
      gap for in-hospital stroke represents a focused opportunity for quality
      improvement. 

PMID- 26288674
TI  - What to do With Wake-Up Stroke.
AB  - Wake-up stroke, defined as the situation where a patient awakens with stroke
      symptoms that were not present prior to falling asleep, represents roughly 1 in 5
      acute ischemic strokes and remains a therapeutic dilemma. Patients with wake-up
      stroke were excluded from most ischemic stroke treatment trials and are often not
      eligible for acute reperfusion therapy in clinical practice, leading to poor
      outcomes. Studies of neuroimaging with standard noncontrast computed tomography
      (CT), magnetic resonance imaging (MRI), and multimodal perfusion-based CT and MRI
      suggest wake-up stroke may occur shortly before awakening and may assist in
      selecting patients for acute reperfusion therapies. Pilot studies of wake-up
      stroke treatment based on these neuroimaging features are promising but have
      limited generalizability. Ongoing randomized treatment trials using neuroimaging
      based patient selection may identify a subset of patients with wake-up stroke
      that can safely benefit from acute reperfusion therapies. 

PMID- 26288676
TI  - Diving into the Ice Bucket Challenge: Intraparenchymal Hemorrhage and the
      Mammalian Diving Reflex.
AB  - Triggered by facial exposure to cold water and apnea, the mammalian diving reflex
      consists of bradycardia and peripheral arteriolar vasoconstriction leading to an
      increase in central arterial pressure. It has been previously associated with
      ischemic stroke but not definitively with intracerebral hemorrhage. We present a
      case of intracerebral hemorrhage occurring in a woman with poorly controlled
      hypertension following her participation in the amyotrophic lateral sclerosis
      fund-raising "Ice Bucket Challenge," in which ice-cold water was poured on her
      head. We suspect that facial exposure to ice-cold water triggered the diving
      reflex, causing a hypertensive surge and ultimately the intracerebral hemorrhage.

PMID- 26288677
TI  - Incentives to Repurpose Existing Drugs for Orphan Indications.
AB  - The Orphan Drug Act has been successful in providing incentives to find cures for
      orphan diseases. However, many orphan diseases are still without cure. Therefore,
      the 114th Congress has introduced the 21st Century Cures Act and the Orphan
      Product Extension Now Accelerating Cures and Treatment Act of 2015 to further
      provide incentives to innovators to repurpose existing drugs for treatment of
      these orphan diseases. However, these bills are currently pending and their
      incentives might not go far enough. 

PMID- 26288678
TI  - Inhibitors of the Renal Outer Medullary Potassium Channel.

PMID- 26288679
TI  - Fused Morphlinopyrimidines and Methods of Use Thereof.

PMID- 26288680
TI  - Fatty Acid Synthase (FASN) Inhibitors as Potential Treatment for Cancer, Obesity,
      and Liver Related Disorders.

PMID- 26288681
TI  - Suppression of Hepatocellular Carcinoma by Inhibition of Overexpressed Ornithine
      Aminotransferase.
AB  - Hepatocellular carcinoma is the second leading cause of cancer death worldwide.
      DNA microarray analysis identified the ornithine aminotransferase (OAT) gene as a
      prominent gene overexpressed in hepatocellular carcinoma (HCC) from Psammomys
      obesus. In vitro studies demonstrated inactivation of OAT by gabaculine (1), a
      neurotoxic natural product, which suppressed in vitro proliferation of two HCC
      cell lines. Alpha-fetoprotein (AFP) secretion, a biomarker for HCC, was
      suppressed by gabaculine in both cell lines, but not significantly. Because of
      the active site similarity between GABA aminotransferase (GABA-AT) and OAT, a
      library of 24 GABA-AT inhibitors was screened to identify a more selective
      inhibitor of OAT. (1S,3S)-3-Amino-4-(hexafluoropropan-2-ylidene)cyclopentane-1
      carboxylic acid (2) was found to be an inactivator of OAT that only weakly
      inhibits GABA-AT, l-aspartate aminotransferase, and l-alanine aminotransferase.
      In vitro administration of 2 significantly suppressed AFP secretion in both Hep3B
      and HepG2 HCC cells; in vivo, 2 significantly suppressed AFP serum levels and
      tumor growth in HCC-harboring mice, even at 0.1 mg/kg. Overexpression of the OAT
      gene in HCC and the ability to block the growth of HCC by OAT inhibitors support
      the role of OAT as a potential therapeutic target to inhibit HCC growth. This is
      the first demonstration of suppression of HCC by an OAT inactivator. 

PMID- 26288682
TI  - Structure-Based Design of Selective Janus Kinase 2 Imidazo[4,5-d]pyrrolo[2,3
      b]pyridine Inhibitors.
AB  - Early hit to lead work on a pyrrolopyridine chemotype provided access to
      compounds with biochemical and cellular potency against Janus kinase 2 (JAK2).
      Structure-based drug design along the extended hinge region of JAK2 led to the
      identification of an important H-bond interaction with the side chain of Tyr 931,
      which improved JAK family selectivity. The 4,5-dimethyl thiazole analogue 18
      demonstrated high levels of JAK family selectivity and was identified as a
      promising lead for the program. 

PMID- 26288683
TI  - Discovery of a Highly Selective JAK2 Inhibitor, BMS-911543, for the Treatment of
      Myeloproliferative Neoplasms.
AB  - JAK2 kinase inhibitors are a promising new class of agents for the treatment of
      myeloproliferative neoplasms and have potential for the treatment of other
      diseases possessing a deregulated JAK2-STAT pathway. X-ray structure and ADME
      guided refinement of C-4 heterocycles to address metabolic liability present in
      dialkylthiazole 1 led to the discovery of a clinical candidate, BMS-911543 (11),
      with excellent kinome selectivity, in vivo PD activity, and safety profile. 

PMID- 26288684
TI  - Discovery of Novel Isatin-Based p53 Inducers.
AB  - A series of isatin Schiff base derivatives were identified during in silico
      screening of the small molecule library for novel activators of p53. The
      compounds selected based on molecular docking results were further validated by a
      high-content screening assay using U2OS human osteosarcoma cells with an
      integrated EGFP-expressing p53-dependent reporter. The hit compounds activated
      and stabilized p53, as shown by Western blotting, at higher rates than the well
      known positive control Nutlin-3. Thus, the p53-activating compounds identified by
      this approach represent useful molecular probes for various cancer studies. 

PMID- 26288685
TI  - Discovery of Triazole CYP11B2 Inhibitors with in Vivo Activity in Rhesus Monkeys.
AB  - Hit-to-lead efforts resulted in the discovery of compound 19, a potent CYP11B2
      inhibitor that displays high selectivity vs related CYPs, good pharmacokinetic
      properties in rat and rhesus, and lead-like physical properties. In a rhesus
      pharmacodynamic model, compound 19 displays robust, dose-dependent aldosterone
      lowering efficacy, with no apparent effect on cortisol levels. 

PMID- 26288686
TI  - Virtual Screening and Biological Validation of Novel Influenza Virus PA
      Endonuclease Inhibitors.
AB  - The influenza virus RNA-dependent RNA polymerase complex (RdRp), a heterotrimeric
      protein complex responsible for viral RNA transcription and replication,
      represents a primary target for antiviral drug development. One particularly
      attractive approach is interference with the endonucleolytic "cap-snatching"
      reaction by the RdRp subunit PA, more precisely by inhibiting its metal-dependent
      catalytic activity which resides in the N-terminal part of PA (PA-Nter). Almost
      all PA inhibitors (PAIs) thus far discovered bear pharmacophoric fragments with
      chelating motifs able to bind the bivalent metal ions in the catalytic core of PA
      Nter. More recently, the availability of crystallographic structures of PA-Nter
      has enabled rational design of original PAIs with improved binding properties and
      antiviral potency. We here present a coupled pharmacophore/docking virtual
      screening approach that allowed us to identify PAIs with interesting inhibitory
      activity in a PA-Nter enzymatic assay. Moreover, antiviral activity in the low
      micromolar range was observed in cell-based influenza virus assays. 

PMID- 26288687
TI  - Modulation of the Interaction between a Peptide Ligand and a G Protein-Coupled
      Receptor by Halogen Atoms.
AB  - Systematic halogenation of two native opioid peptides has shown that halogen
      atoms can modulate peptide-receptor interactions in different manners. First,
      halogens may produce a steric hindrance that reduces the binding of the peptide
      to the receptor. Second, chlorine, bromine, or iodine may improve peptide binding
      if their positive sigma-hole forms a halogen bond interaction with negatively
      charged atoms of the protein. Lastly, the negative electrostatic potential of
      fluorine can interact with positively charged atoms of the protein to improve
      peptide binding. 

PMID- 26288688
TI  - Novel Lobophorins Inhibit Oral Cancer Cell Growth and Induce Atf4- and Chop
      Dependent Cell Death in Murine Fibroblasts.
AB  - As part of the International Cooperative Biodiversity Groups (ICBG) Program, we
      were interested in identifying biologically active unfolded protein response
      (UPR) inducing compounds from marine microorganisms isolated from Costa Rican
      biota. With this aim in mind we have now generated more than 33,000 unique
      prefractionated natural product extracts from marine and terrestrial organisms
      that have been submitted to the Center of Chemical Genomics (CCG) at the
      University of Michigan for high throughput screening (HTS). An effective
      complementary cell-based assay to identify novel modulators of UPR signaling was
      used for screening extracts. Active fractions were iteratively subjected to
      reverse-phase HPLC chromatographic analysis, and together with lobophorin A, B,
      E, and F (1-4), three new lobophorin congeners, designated as CR1 (5), CR2 (6),
      and CR3 (7) were isolated. Herein, we report that secondary assays revealed that
      the new lobophorins induced UPR-associated gene expression, inhibited oral
      squamous cell carcinoma cell growth, and led to UPR-dependent cell death in
      murine embryonic fibroblast (MEF) cells. 

PMID- 26288689
TI  - Discovery of Potent and Selective Inhibitors for ADAMTS-4 through DNA-Encoded
      Library Technology (ELT).
AB  - The aggrecan degrading metalloprotease ADAMTS-4 has been identified as a novel
      therapeutic target for osteoarthritis. Here, we use DNA-encoded Library
      Technology (ELT) to identify novel ADAMTS-4 inhibitors from a DNA-encoded
      triazine library by affinity selection. Structure-activity relationship studies
      based on the selection information led to the identification of potent and highly
      selective inhibitors. For example, 4-(((4-(6,7-dimethoxy-3,4-dihydroisoquinolin
      2(1H)-yl)-6-(((4-methylpiperazin-1-yl)methyl)amino)-1,3,5-triazin-2
      yl)amino)methyl)-N-ethyl-N-(m-tolyl)benzamide has IC50 of 10 nM against ADAMTS-4,
      with >1000-fold selectivity over ADAMT-5, MMP-13, TACE, and ADAMTS-13. These
      inhibitors have no obvious zinc ligand functionality. 

PMID- 26288690
TI  - Highly Efficient Synthesis of 1,3-Dihydroxy-2-carboxycarbazole and Its
      Neuroprotective Effects.
AB  - Carbazoles represent a family of tricyclic compounds that widely appeared in
      nature. Numerous studies have revealed a diverse array of bioactivity associated
      with this scaffold. In the present study, a novel and highly efficient
      methodology for preparing 1,3-dihydroxy-2-carboxycarbazole from indole-3-acetic
      acid and Meldrum's acid was developed. Furthermore, biological characterization
      demonstrated that this multisubstituted carbazole analogue exhibited inhibitory
      activity on Abeta aggregation, antioxidative properties, and promising
      neuroprotective activities in a cellular model of Alzheimer's disease, thus
      further supporting the valuable application of this synthetic methodology in
      search for effective neuroprotectants. 

PMID- 26288691
TI  - Styrylphenylphthalimides as Novel Transrepression-Selective Liver X Receptor
      (LXR) Modulators.
AB  - Anti-inflammatory effects of liver X receptor (LXR) ligands are thought to be
      largely due to LXR-mediated transrepression, whereas side effects are caused by
      activation of LXR-responsive gene expression (transactivation). Therefore,
      selective LXR modulators that preferentially exhibit transrepression activity
      should exhibit anti-inflammatory properties with fewer side effects. Here, we
      synthesized a series of styrylphenylphthalimide analogues and evaluated their
      structure-activity relationships focusing on LXRs-transactivating
      agonistic/antagonistic activities and transrepressional activity. Among the
      compounds examined, 17l showed potent LXR-transrepressional activity with high
      selectivity over transactivating activity and did not show characteristic side
      effects of LXR-transactivating agonists in cells. This representative compound,
      17l, was confirmed to have LXR-dependent transrepressional activity and to bind
      directly to LXRbeta. Compound 17l should be useful not only as a chemical tool
      for studying the biological functions of LXRs transrepression but also as a
      candidate for a safer agent to treat inflammatory diseases. 

PMID- 26288692
TI  - Discovery of BMS-641988, a Novel Androgen Receptor Antagonist for the Treatment
      of Prostate Cancer.
AB  - BMS-641988 (23) is a novel, nonsteroidal androgen receptor antagonist designed
      for the treatment of prostate cancer. The compound has high binding affinity for
      the AR and acts as a functional antagonist in vitro. BMS-641988 is efficacious in
      multiple human prostate cancer xenograft models, including CWR22-BMSLD1 where it
      displays superior efficacy relative to bicalutamide. Based on its promising
      preclinical profile, BMS-641988 was selected for clinical development. 

PMID- 26288693
TI  - Structure-Based Design of GNE-495, a Potent and Selective MAP4K4 Inhibitor with
      Efficacy in Retinal Angiogenesis.
AB  - Diverse biological roles for mitogen-activated protein kinase kinase kinase
      kinase 4 (MAP4K4) have necessitated the identification of potent inhibitors in
      order to study its function in various disease contexts. In particular, compounds
      that can be used to carry out such studies in vivo would be critical for
      elucidating the potential for therapeutic intervention. A structure-based design
      effort coupled with property-guided optimization directed at minimizing the
      ability of the inhibitors to cross into the CNS led to an advanced compound 13
      (GNE-495) that showed excellent potency and good PK and was used to demonstrate
      in vivo efficacy in a retinal angiogenesis model recapitulating effects that were
      observed in the inducible Map4k4 knockout mice. 

PMID- 26288694
TI  - Discovery, SAR, and X-ray Binding Mode Study of BCATm Inhibitors from a Novel DNA
      Encoded Library.
AB  - As a potential target for obesity, human BCATm was screened against more than 14
      billion DNA encoded compounds of distinct scaffolds followed by off-DNA synthesis
      and activity confirmation. As a consequence, several series of BCATm inhibitors
      were discovered. One representative compound (R)-3-((1-(5-bromothiophene-2
      carbonyl)pyrrolidin-3-yl)oxy)-N-methyl-2'-(methylsulfonamido)-[1,1'-biphenyl]-4
      carboxamide (15e) from a novel compound library synthesized via on-DNA Suzuki
      Miyaura cross-coupling showed BCATm inhibitory activity with IC50 = 2.0 MUM. A
      protein crystal structure of 15e revealed that it binds to BCATm within the
      catalytic site adjacent to the PLP cofactor. The identification of this novel
      inhibitor series plus the establishment of a BCATm protein structure provided a
      good starting point for future structure-based discovery of BCATm inhibitors. 

PMID- 26288695
TI  - Probing Mechanisms of CYP3A Time-Dependent Inhibition Using a Truncated Model
      System.
AB  - Time-dependent inhibition (TDI) of cytochrome P450 (CYP) enzymes may incur
      serious undesirable drug-drug interactions and in rare cases drug-induced
      idiosyncratic toxicity. The reactive metabolites are often generated through
      multiple sequential biotransformations and form adducts with CYP enzymes to
      inactivate their function. The complexity of these processes makes addressing TDI
      liability very challenging. Strategies to mitigate TDI are therefore highly
      valuable in discovering safe therapies to benefit patients. In this Letter, we
      disclose our simplified approach toward addressing CYP3A TDI liabilities, guided
      by metabolic mechanism hypotheses. By adding a methyl group onto the alpha carbon
      of a basic amine, TDI activities of both the truncated and full molecules (7a and
      11) were completely eliminated. We propose that truncated molecules, albeit with
      caveats, may be used as surrogates for full molecules to investigate TDI. 

PMID- 26288696
TI  - Structural Insights Lead to a Negamycin Analogue with Improved Antimicrobial
      Activity against Gram-Negative Pathogens.
AB  - Negamycin is a natural product with antibacterial activity against a broad range
      of Gram-negative pathogens. Recent revelation of its ribosomal binding site and
      mode of inhibition has reinvigorated efforts to identify improved analogues with
      clinical potential. Translation-inhibitory potency and antimicrobial activity
      upon modification of different moieties of negamycin were in line with its
      observed ribosomal binding conformation, reaffirming stringent structural
      requirements for activity. However, substitutions on the N6 amine were tolerated
      and led to N6-(3-aminopropyl)-negamycin (31f), an analogue showing 4-fold
      improvement in antibacterial activity against key bacterial pathogens. This
      represents the most potent negamycin derivative to date and may be a stepping
      stone toward clinical development of this novel antibacterial class. 

PMID- 26288697
TI  - Design of Potent and Orally Active GPR119 Agonists for the Treatment of Type II
      Diabetes.
AB  - We report herein the design and synthesis of a series of potent and selective
      GPR119 agonists. Our objective was to develop a GPR119 agonist with properties
      that were suitable for fixed-dose combination with a DPP4 inhibitor. Starting
      from a phenoxy analogue (1), medicinal chemistry efforts directed toward reducing
      half-life and increasing solubility led to the synthesis of a series of benzyloxy
      analogues. Compound 28 was chosen for further profiling because of its favorable
      physicochemical properties and excellent GPR119 potency across species. This
      compound exhibited a clean off-target profile in counterscreens and good in vivo
      efficacy in mouse oGTT. 

PMID- 26288698
TI  - Discovery and Structure Enabled Synthesis of 2,6-Diaminopyrimidin-4-one IRAK4
      Inhibitors.
AB  - We report the identification and synthesis of a series of aminopyrimidin-4-one
      IRAK4 inhibitors. Through high throughput screening, an aminopyrimidine hit was
      identified and modified via structure enabled design to generate a new, potent,
      and kinase selective pyrimidin-4-one chemotype. This chemotype is exemplified by
      compound 16, which has potent IRAK4 inhibition activity (IC50 = 27 nM) and
      excellent kinase selectivity (>100-fold against 99% of 111 tested kinases), and
      compound 31, which displays potent IRAK4 activity (IC50 = 93 nM) and good rat
      bioavailability (F = 42%). 

PMID- 26288699
TI  - High-Throughput Screening of Patient-Derived Cultures Reveals Potential for
      Precision Medicine in Glioblastoma.
AB  - Identifying drugs for the treatment of glioblastoma (GBM), a rapidly fatal
      disease, has been challenging. Most screening efforts have been conducted with
      immortalized cell lines grown with fetal bovine serum, which have little
      relevance to the genomic features found in GBM patients. Patient-derived
      neurosphere cultures, while being more physiologically relevant, are difficult to
      screen and therefore are only used to test a few drug candidates after initial
      screening efforts. Laminin has been used to generate two-dimensional cell lines
      from patient tumors, preserving the genomic signature and alleviating some
      screening hurdles. We present here the first side-by-side comparison of inhibitor
      sensitivity of laminin and neurosphere-grown patient-derived GBM cell lines and
      show that both of these culture methods result in the same pattern of inhibitor
      sensitivity. We used these screening methods to evaluate the dependencies of
      seven patient-derived cell models: three grown on laminin and four grown as
      neurospheres, against 56 agents in 17-point dose-response curves in 384-well
      format in triplicate. This allowed us to establish differential sensitivity of
      chemotherapeutic agents across the seven patient-derived models. We found that
      MEK inhibition caused patient-sample-specific growth inhibition and that
      bortezomib, an FDA-approved proteasome inhibitor, was potently lethal in all
      patient-derived models. Furthermore, the screening results led us to test the
      combination of the Bcl-2 inhibitor ABT-263, and the mTOR inhibitor AZD-8055,
      which we found to be synergistic in a subset of patient-derived GBM models. Thus,
      we have identified new candidate therapeutics and developed a high-throughput
      screening system using patient-derived GBM samples. 

PMID- 26288700
TI  - Mini-review: Strategies for Variation and Evolution of Bacterial Antigens.
AB  - Across the eubacteria, antigenic variation has emerged as a strategy to evade
      host immunity. However, phenotypic variation in some of these antigens also
      allows the bacteria to exploit variable host niches as well. The specific
      mechanisms are not shared-derived characters although there is considerable
      convergent evolution and numerous commonalities reflecting considerations of
      natural selection and biochemical restraints. Unlike in viruses, mechanisms of
      antigenic variation in most bacteria involve larger DNA movement such as gene
      conversion or DNA rearrangement, although some antigens vary due to point
      mutations or modified transcriptional regulation. The convergent evolution that
      promotes antigenic variation integrates various evolutionary forces: these
      include mutations underlying variant production; drift which could remove alleles
      especially early in infection or during life history phases in arthropod vectors
      (when the bacterial population size goes through a bottleneck); selection not
      only for any particular variant but also for the mechanism for the production of
      variants (i.e., selection for mutability); and overcoming negative selection
      against variant production. This review highlights the complexities of drivers of
      antigenic variation, in particular extending evaluation beyond the commonly cited
      theory of immune evasion. A deeper understanding of the diversity of purpose and
      mechanisms of antigenic variation in bacteria will contribute to greater insight
      into bacterial pathogenesis, ecology and coevolution with hosts. 

PMID- 26288703
TI  - Validity and Reliability of the Persian Version of Shortened Disabilities of the
      Arm, Shoulder and Hand Questionnaire (Quick-DASH).
AB  - BACKGROUND: The aim was to assess the validity and reliability of the Persian
      version of shortened disabilities of the arm, shoulder, and hand (Quick-DASH)
      questionnaire in patients with upper extremity conditions. METHODS: We
      administered the Persian version of Quick-DASH to 202 patients with upper
      extremity conditions, of which 71 patients randomly returned after 3 days to
      respond to the questionnaire for the 2(nd) time. In order to test the construct
      validity of the questionnaire, patients responded to the Michigan Hand Outcome
      Questionnaire (MHOQ) and Short Form 36 Health Survey (SF-36) as well. Internal
      consistency was tested using the Cronbach's alpha, and test-retest reliability
      was measured using intra-class correlation coefficient (ICC). RESULTS: Cronbach's
      alpha was 0.90. ICC was 0.89. Convergent validity was confirmed, as the Spearman
      correlation between the Quick-DASH and MHOQ was 0.67 and ranged from 0.24 to 0.56
      between the subscales of the SF-36 and Quick-DASH. CONCLUSIONS: Observation of
      excellent internal consistency, good to excellent test-retest reliability, and
      moderate to strong construct validity confirms the validity and reliability of
      the Persian version of Quick-DASH for evaluating the magnitude and level of
      disability in upper extremity conditions.

PMID- 26288702
TI  - Nonpreventive Role of Aerobic Exercise Against Cisplatin-induced Nephrotoxicity
      in Female Rats.
AB  - BACKGROUND: Cisplatin (CP) is a chemotherapy drug and nephrotoxicity is a major
      concern for CP therapy. CP-induced nephrotoxicity is gender-dependent, and the
      effect of aerobic exercise in females has not been reported yet while it has a
      beneficial effect in males. Hence, this study was designed to determine the
      protective role of aerobic exercise against CP-induced nephrotoxicity in female
      rats. METHODS: Twenty-eight adult female rats were divided into four groups.
      Groups I and II had aerobic exercise on a treadmill for 8 weeks. Then, the
      exercise protocol was continued for another week in group I and stopped in group
      II. All animals in these groups received CP (2.5 mg/kg/day; i.p.) for 1-week.
      Groups III and IV were treated with CP and vehicle, respectively, without
      exercise. Finally, the animals were sacrificed for biochemical measurements and
      tissue histopathology investigations. RESULTS: CP alone without exercise
      increased serum levels of blood urea nitrogen (BUN) and creatinine (Cr), kidney
      weight, and kidney tissue damage score (KTDS); while exercise could not attenuate
      these parameters in female rats. Exercise in females increased the serum levels
      of BUN and Cr and KTDS and weight loss (P < 0.05). Kidney nitrite levels reduce
      significantly in group I in compared to positive and negative control groups.
      Exercise also did not have beneficial effects on malondialdehyde levels in plasma
      and kidney. CONCLUSIONS: Aerobic exercise cannot reduce CP-induced nephrotoxicity
      in female rats. Increasing the damage in female rats may be related to female sex
      hormone estrogen or gender differences in renal hemodynamic and renin-angiotensin
      system activity in the presence of exercise. In general, it is recommended that
      the females under CP chemotherapy avoid exercising during treatment.

PMID- 26288701
TI  - Circadian systems biology: When time matters.
AB  - The circadian clock is a powerful endogenous timing system, which allows
      organisms to fine-tune their physiology and behaviour to the geophysical time.
      The interplay of a distinct set of core-clock genes and proteins generates
      oscillations in expression of output target genes which temporally regulate
      numerous molecular and cellular processes. The study of the circadian timing at
      the organismal as well as at the cellular level outlines the field of
      chronobiology, which has been highly interdisciplinary ever since its origins.
      The development of high-throughput approaches enables the study of the clock at a
      systems level. In addition to experimental approaches, computational clock models
      exist which allow the analysis of rhythmic properties of the clock network. Such
      mathematical models aid mechanistic understanding and can be used to predict
      outcomes of distinct perturbations in clock components, thereby generating new
      hypotheses regarding the putative function of particular clock genes.
      Perturbations in the circadian timing system are linked to numerous molecular
      dysfunctions and may result in severe pathologies including cancer. A
      comprehensive knowledge regarding the mechanistic of the circadian system is
      crucial to develop new procedures to investigate pathologies associated with a
      deregulated clock. In this manuscript we review the combination of experimental
      methodologies, bioinformatics and theoretical models that have been essential to
      explore this remarkable timing-system. Such an integrative and interdisciplinary
      approach may provide new strategies with regard to chronotherapeutic treatment
      and new insights concerning the restoration of the circadian timing in clock
      associated diseases. 

PMID- 26288705
TI  - Towards prevention of hypertension in Nigeria: a study of prehypertension and its
      associations among apparently healthy adults in Umuahia, South-East Nigeria.
AB  - BACKGROUND: The prevalence of hypertension is on the increase in Nigeria.
      Prehypertension is considered a precursor of hypertension and a predictor of
      excessive cardiovascular risk. Identifying individuals with prehypertension and
      initiating effective measures will aid in reducing the incidence and prevalence
      of hypertension in our environment. The aim of this study was to quantify the
      magnitude of prehypertension and determine its associations among adults in a
      representative semi-urban Nigerian population. METHODS: A cross-sectional study
      which was carried out in a semi-urban setting in Southeast Nigeria. Blood
      pressure (BP) was measured using the standard methods. A cardiovascular risk
      factor screening based on physical characteristics, individual medical, and
      family history of participants was done. RESULTS: There were a total of 389
      participants comprising 223 (57.3%) males and 116 (42.7%) females; male:female
      ratio been 1.9:1. The prevalence of prehypertension and hypertension were 45.5%
      and 37.8%, respectively. Males were significantly more likely to have
      prehypertension than females (61% vs. 39% respectively; OR = 1.32, P = 0.03).
      There was a weak positive significant correlation between age and both systolic
      (r = 0.16, P < 0.01) and diastolic (r = 0.12, P = 0.02) blood pressures. Up to
      72.6% of individuals with prehypertension have abnormal body mass index (BMI).
      While up to 8.5% of the participants had a family history of cardiovascular
      disease, 20.3%, and 17.3% had a history of significant intake of alcohol and
      smoking, respectively. CONCLUSIONS: The prevalence of prehypertension in the
      community was high. It was associated with increasing age, male gender, and
      increasing BMI. Interventions at this stage may aid in stemming the rising
      prevalence of hypertension in our environment.

PMID- 26288704
TI  - Effect of L-arginine and L-NAME on Kidney Tissue Damage in Rats after 24 h of
      Bilateral Ureteral Obstruction.
AB  - BACKGROUND: Bilateral ureteral obstruction (BUO) affects renal function
      adversely. Previous investigations have implied that nitric oxide (NO) improves
      renal function in obstructive nephropathy. The aim of the current study was to
      investigate the role of NO precursor, L-arginine, and NO blocker agent, L-NAME on
      kidney tissue damage in rats after 24 h of BUO. METHODS: Forty Wistar rats (18
      male, 22 female) were divided into four groups as follows; group 1: Sham or
      negative control group that received saline 3 days prior to the sham operation,
      group 2: Vehicle or positive control group that received saline 3 days prior to
      BUO, and groups 3 and 4: L-arginine and L-NAME groups that were treated same as
      group 2 except L-arginine (300 mg/kg) and L-NAME (4 mg/kg) instead of saline,
      respectively. Twenty-four hours after obstruction, the serum levels of blood urea
      nitrogen (BUN), creatinine (Cr), nitrite, and malondialdehyde (MDA) as well as
      kidney tissue levels of nitrite and MDA were measured and histopathological
      studies were done on left kidney. RESULTS: The serum levels of BUN and Cr and
      kidney and body weights increased and the tissue levels of MDA and nitrite
      decreased significantly in all BUO groups (P < 0.05). However, the tissue damage
      score was significantly lower in the L-arginine treated group in comparison to
      the vehicle and L-NAME groups (P < 0.05). As expected, the serum level of nitrite
      significantly increased in the L-arginine group (P < 0.05). CONCLUSIONS:
      Endogenous NO donor; L-arginine, may protect the kidney tissue against BUO.
      However, this renoprotective role of L-arginine did not attenuate the increased
      kidney function markers (BUN and Cr) induced by obstruction.

PMID- 26288706
TI  - The Effect of Multi mineral-Vitamin D Supplementation on Pregnancy Outcomes in
      Pregnant Women at Risk for Pre-eclampsia.
AB  - BACKGROUND: The objective of this study was to determine the favorable effects of
      multi mineral-Vitamin D supplementation on pregnancy outcomes among women at risk
      for pre-eclampsia. METHODS: This randomized double-blind controlled clinical
      trial was conducted among 46 women at risk for pre-eclampsia at 27 weeks'
      gestation with positive roll-over test. Pregnant women were randomly assigned to
      receive either the multi mineral-Vitamin D supplements (n = 23) or the placebo (n
      = 23) for 9-week. Multi mineral-Vitamin D supplements were containing 800 mg
      calcium, 200 mg magnesium, 8 mg zinc, and 400 IU Vitamin D3. Fasting blood
      samples were taken at baseline and after 9-week intervention to measure related
      factors. Newborn's outcomes were determined. RESULTS: Although no significant
      difference was seen in newborn's weight and head circumference between the two
      groups, mean newborns' length (51.3 +/- 1.7 vs. 50.3 +/- 1.2 cm, P = 0.03) was
      significantly higher in multi mineral-Vitamin D group than that in the placebo
      group. Compared to the placebo, consumption of multi mineral-Vitamin D
      supplements resulted in increased levels of serum calcium (+0.19 vs. -0.08 mg/dL,
      P = 0.03), magnesium (+0.15 vs. -0.08 mg/dL, P = 0.03), zinc (+8.25 vs. -21.38
      mg/dL, P = 0.001) and Vitamin D (+3.79 vs. -1.37 ng/ml, P = 0.01). In addition,
      taking multi mineral-Vitamin D supplements favorably influenced systolic blood
      pressure (SBP) (-1.08 vs. 6.08 mmHg, P = 0.001) and diastolic blood pressure
      (DBP) (-0.44 vs. 3.05 mmHg, P = 0.02). CONCLUSIONS: Multi mineral-Vitamin D
      supplementation for 9-week in pregnant women at risk for pre-eclampsia resulted
      in increased newborn's length, increased circulating levels of maternal serum
      calcium, magnesium, zinc and Vitamin D, and led to decreased maternal SBP and
      DBP.

PMID- 26288707
TI  - Cost-effectiveness Analysis of Cetuximab in Treatment of Metastatic Colorectal
      Cancer in Iranian Pharmaceutical Market.
AB  - BACKGROUND: Cetuximab is a monoclonal antibody which acts against the epidermal
      growth-factor receptor. Randomized controlled trials show that the addition of
      cetuximab to folinic acid, 5-flourouracil, irinotecan (FOLFIRI), folinic acid, 5
      flourouracil, oxaliplatin (FOLFOX) and capecitabin + oxaliplatin (CAPOX)
      regimens, as the first-line treatment for metastatic colorectal cancer (CRC),
      increases the overall survival (OS) and progression-free survival (PFS) compared
      to FOLFIRI, FOLFOX and CAPOX regimens alone. The aim of this study was to analyze
      the cost-effectiveness of different treatment programs for managing metastatic
      CRC with and without cetuximab in the first-line treatment of unresectable
      metastatic CRC in Iran. METHODS: A systematic search of the literature was
      performed in PubMed, Centre for Reviews and Dissemination Databases and Cochrane
      Library to assess the effectiveness of the drug in the context of PFS, OS and the
      adverse events. The incremental cost-effectiveness ratio of each treatment
      program was calculated. An extensive sensitivity analysis was conducted on the
      results regarding the effectiveness. RESULTS: The addition of cetuximab to
      FOLFIRI, FOLFOX and CAPOX programs increased PFS by 0.1, 0.042 and 0.042 years,
      respectively. Similarly, the addition of cetuximab to FOLFIRI, FOLFOX and CAPOX
      increased OS by 0.325, 0.442 and 0.442 years and also cost $212825, $202484 and
      $204198 individually. Whereas, based on the World Health Organisation (WHO)
      suggested threshold for cost-effectiveness analysis, even FOLFOX + cetuximab was
      very higher than the threshold in Iran (37.4 times higher). CONCLUSIONS: The
      FOLFOX regimen + cetuximab provides lower costs per additional life years gained
      (more cost-effective) compared with its alternatives in the treatment of patients
      with unresectable metastatic CRC. However, according to the WHO indicator, none
      of the cetuximab regimens could be considered as cost effective for the Iranian
      health care market.

PMID- 26288708
TI  - The Epidemiology of Skin Cancer and its Trend in Iran.
AB  - BACKGROUND: One of the most common cancers is skin cancer worldwide. Since
      incidence and cost of treatment of the cancer are increasing, it is necessary to
      further investigate to prevent and control this disease. This study aimed to
      determine skin cancer trend and epidemiology in Iran. METHODS: This study was
      done based on existing data. Data used in this study were obtained from a
      national registry of cancer cases and the Disease Management Center of Ministry
      of Health in Iran. All cases registered in the country were included during 2004
      2008. Incidence rates were reported based on the direct method and standard
      population of World Health Organization. RESULTS: Based on the results of this
      study, the incidence of skin cancer is rising in Iran and the sex ratio was more
      in men than women in all provinces. The age-standardized incidence rate (ASR) of
      skin cancer was highest in males in Semnan, Isfahan, and Hamedan provinces (34.9,
      30.80, and 28.84, respectively). The highest ASRs were seen in females in Semnan,
      Yazd, and Isfahan provinces (26.7, 24.14, and 18.97, respectively). The lowest
      ASR in male was observed in Sistan and Baluchestan, and in female in Hormozgan
      provinces. CONCLUSIONS: The incidence of skin cancer is increasing in the
      country. Therefore, the plan for the control and prevention of this cancer must
      be a high priority for health policy makers.

PMID- 26288709
TI  - Vitamins A and E Deficiencies among Pregnant Women Attending Antenatal Care at
      General Hospital Dawakin Kudu, North-West Nigeria.
AB  - BACKGROUND: Vitamins A and E deficiency is prevalent in developing countries, and
      plasma levels are low in pregnancy. This study was undertaken to determine the
      serum Vitamins A and E status among pregnant women attending antenatal care at a
      General Hospital in Dawakin Kudu, Kano and to provide the necessary information
      needed to suggest the supplementation of Vitamins A and E during pregnancy.
      METHODS: The study was done in General Hospital Dawakin Kudu Local Government
      Area. Dawakin Kudu, a rural community in Kano State is about 12 km from Kano
      metropolis which is the most populous city in Nigeria and commercial nerve center
      of Northern Nigeria. Most of the women are housewives, however, some engage in
      subsistent farming and petty trading. This was a prospective study of 200
      pregnant women at various maternal ages, gestational ages, and parities. Informed
      consent was obtained from the participants. Research structured questionnaire was
      administered to 200 respondents which showed age and parity distributions.
      Determination of Serum Vitamins A and E was done using methods of Bessey, et al.
      and Tsen. Ethical approval for the research was obtained from General Hospital,
      Dawakin Kudu, Kano. STATISTICAL ANALYSIS USED: Data obtained were analyzed using
      SPSS version 17 statistical software (SPSS Inc., IL, Chicago, USA). Descriptive
      statistics was done. Mean serum Vitamins A and E concentration between trimesters
      were compared using two-way ANOVA and P < 0.05 was considered statistically
      significant. RESULTS: Majority of the women were aged 20-39 years with mean of
      23.67 +/- 6.11. Most were in the 1-4 parity range. Mean birth weight was 2.42 +/-
      0.74 kg. Above 65% were deficient while 34.5% had normal levels of Vitamin A and
      51% were deficient of serum Vitamin E. Serum Vitamins A and E levels showed a
      marked reduction from first through third trimester. The differences were
      statistically significant (P < 0.05). CONCLUSIONS: There is a significant
      reduction in the serum Vitamins A and E concentration throughout the period of
      pregnancy with the highest levels in the first trimester. Therefore, further
      studies should evaluate the value of Vitamins A and E supplementation during
      pregnancy especially for those whose fruit and vegetable consumption is
      inadequate.

PMID- 26288710
TI  - Associations between Self-medication, Health Literacy, and Self-perceived Health
      Status: A Community-Based Study.
AB  - BACKGROUND: Although the frequency of self-medication has been well-documented in
      the public health literature, but no study has examined the relationship between
      health literacy and self-medication yet. This study was aimed to investigating
      the relationship between health literacy and self-medication in a community-based
      study. METHODS: This cross-sectional study was conducted on 924 adults to survey
      association between health literacy and self-medication among peoples in Ardabil
      city in 2014 who were selected using a multi-stage random sampling method. Health
      literacy was measured by the test of functional health literacy in adults and
      general health status was measured by the 12-item General Health Questionnaire,
      and self-reported self-medication (overall, sedative, antibiotic and herbal) in
      last 3 months was assessed. All statistical analysis was performed using the SPSS
      version 18 and a P < 0.05 was considered significant. RESULTS: The mean age and
      weight of respondents were 37 years and 74.7 kg, respectively. The prevalence of
      self-medication was 61.6%, and the percentage of self-administering antibiotics,
      sedative, and herbal medicines were 40%, 54.4%, and 59.1% in the last 3 months,
      respectively. Significant relationship was found between of total health literacy
      and general health status with self-medication. The prevalence of self-medication
      among participants with poor and very poor self-rated physical and mental health
      was significantly higher than other participants (P < 0.001). CONCLUSIONS: Self
      medication had a significant relationship with health literacy and health status.
      Therefore, the design and implementation of training programs are necessary to
      increase the perception on the risk of self-medication.

PMID- 26288711
TI  - Obinutuzumab for the treatment of patients with previously untreated chronic
      lymphocytic leukemia: overview and perspective.
AB  - Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative
      disorder in the Western world and predominantly affects older people. Until
      recently, most studies in CLL focused on younger patients in whom intensive
      therapy with the addition of rituximab to fludarabine and cyclophosphamide was
      shown to improve survival. Obinutuzumab is a novel type II anti-CD20 monoclonal
      antibody (mAb) that recently demonstrated an overall survival advantage when
      combined with chemotherapy in previously untreated older patients with CLL and
      comorbidities. Obinutuzumab was superior to rituximab in this same study in terms
      of response rates and progression-free survival. Several preclinical and early
      phase clinical studies also support the efficacy of obinutuzumab. The most
      frequent adverse event noted with obinutuzumab is infusion-related reactions,
      which occur more frequently than with rituximab and are typically restricted to
      the first cycle of therapy. Based on these results, obinutuzumab should be
      considered the gold standard mAb for combination with chemotherapy in previously
      untreated patients with CLL and comorbidities. The marked efficacy of
      obinutuzumab with a weak chemotherapy backbone implies significant potency of
      this mAb, making it the ideal partner for combination studies with other agents
      in CLL. 

PMID- 26288712
TI  - Advances and challenges in the management of complement-mediated thrombotic
      microangiopathies.
AB  - Complement activation plays a major role in several renal pathophysiological
      conditions. The three pathways of complement lead to C3 activation, followed by
      the formation of the anaphylatoxin C5a and the terminal membrane attack complex
      (MAC) in blood and at complement activating surfaces, lead to a cascade of events
      responsible for inflammation and for the induction of cell lysis. In case of
      ongoing uncontrolled complement activation, endothelial cells activation takes
      place, leading to events in which at the end thrombotic microangiopathy can
      occur. Atypical haemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy
      characterized by excessive complement activation on the surface of the
      microcirculation. It is a severe, rare disease which leads to end-stage renal
      failure (ESRF) and/or to death in more than 50% of patients without treatment. In
      the first decade of the second millennium, huge progress in understanding the
      aetiology of this disease was made, which paved the way to better treatment.
      First, protocols of plasma therapy for treatment, prevention of relapses and for
      renal transplantation in those patients were set up. Secondly, in some severe
      cases, combined kidney and liver transplantation was reported. Finally, at the
      end of this decade, the era of complement inhibitors, as anti-C5 monoclonal
      antibody (anti-C5 mAb) began. The past five years have seen growing evidence of
      the favourable effect of anti-C5 mAb in aHUS which has made this drug the first
      line treatment in this disease. The possible complication of meningococcal
      infection needs appropriate vaccination before its use. Unfortunately, the
      worldwide use of anti-C5 mAb is limited by its very high price. In the future,
      extension of indications for anti-C5 mAb use, the elaboration of generics and of
      mAbs directed towards other complement factors of the terminal pathway of the
      complement system might succeed in reducing the cost of this new valuable
      therapeutic approach and render it available worldwide for patients from all
      social classes. 

PMID- 26288714
TI  - Belinostat in patients with refractory or relapsed peripheral T-cell lymphoma: a
      perspective review.
AB  - Peripheral T-cell lymphoma (PTCL) is a disease with poor prognosis and limited
      treatment options. Recent advances in cancer biology suggest that PTCL may be
      characterized by gross epigenetic dysregulation, which may help explain its
      sensitivity to histone deacetylase (HDAC) inhibitors. HDAC inhibitors have
      demonstrated significant activity in T-cell neoplasms and recently, the BELIEF
      trial evaluated belinostat leading to its approval in the US. This review
      discusses the development of belinostat, its mechanism of action, pivotal
      clinical trials, drug toxicity and its recent approval for patients with relapsed
      or refractory PTCL. Key clinical trials covered include phase I/II evaluation of
      belinostat in hematologic malignancies, cutaneous T-cell lymphoma (CTCL) and
      PTCL. In addition, the BELIEF trial in PTCL leading to FDA approval of belinostat
      is reviewed in detail. 

PMID- 26288713
TI  - Clinical potential of pacritinib in the treatment of myelofibrosis.
AB  - Myelofibrosis (MF) is a myeloid disorder caused by a clonal hematopoietic stem
      cell proliferation associated with activation of the Janus kinase (JAK) signal
      transducer and activator of transcription (STAT) signaling pathways. Patients
      with MF often develop severe splenomegaly, marked symptom burden and significant
      cytopenias, with a consequent marked negative impact on quality of life and
      survival. The management of MF patients has dramatically improved with the
      development of a group of drugs that inhibit JAK signaling. The first of these
      agents to be approved was ruxolitinib, a JAK1/JAK2 inhibitor, which has been
      shown to improve both spleen size and symptoms in patients with MF. However,
      myelotoxicity, particularly of the platelet lineage, significantly limits the
      patient population who can benefit from this agent. Thus, there is an unmet need
      for novel agents with limited myelotoxicity to treat MF. Pacritinib, a JAK2 and
      FMS-like tyrosine kinase 3 (FLT3) inhibitor, has shown promising results in early
      phase trials with limited myelotoxicity and clinical responses that are
      comparable with those seen with ruxolitinib, even in patients with severe
      thrombocytopenia. Currently there are two large phase III clinical trials of
      pacritinib in MF, including patients with thrombocytopenia, and those previously
      treated with ruxolitinib. If the encouraging results observed in early phase
      clinical trials are confirmed, pacritinib will represent a new and exciting
      treatment option for patients with MF and particularly patients with significant
      cytopenias. 

PMID- 26288715
TI  - Current controversies in the diagnosis and management of von Willebrand disease.
AB  - Von Willebrand disease (VWD) is the most common inherited bleeding disorder in
      the world. The spectrum of VWD spans quantitative and qualitative deficiencies of
      von Willebrand factor (VWF), a platelet adhesive protein. It manifests primarily
      as mucocutaneous bleeding, but severely affected patients may suffer soft tissue
      bleeding and hemarthroses. There is disagreement in the multiple guidelines
      published regarding diagnosis, especially of type 1 VWD, which also remains the
      most opaque with respect to molecular characterization. Treatment with
      desmopressin (DDAVP) is most effective in type 1 VWD, but regimens are not
      standardized. It is not clear which type 2 VWD patients with qualitative
      deficiencies can be treated with DDAVP and which ones should receive VWF
      concentrates. No guidelines stipulate which patients might benefit from
      prophylactic VWF infusions and how they should be dosed. These are some current
      controversies in VWD that are discussed in this review. 

PMID- 26288716
TI  - Seasonal variation of immune thrombocytopenic purpura related hospitalizations
      among adults in the USA: analysis of the nationwide inpatient sample database.

PMID- 26288718
TI  - Creating patient-centered health care systems to improve outcomes and reduce
      disparities.
AB  - Health care delivery systems that are designed to understand and meet patient
      preferences for care have the potential to improve health outcomes and reduce
      disparities. Studies that rigorously assess patient care preferences in minority
      and underserved populations, stakeholder engagement, and policies that promote a
      diverse health care workforce that can address patient preferences are important
      levers for improving care for vulnerable populations. 

PMID- 26288717
TI  - The biological role of actinin-4 (ACTN4) in malignant phenotypes of cancer.
AB  - Invasion and metastasis are malignant phenotypes in cancer that lead to patient
      death. Cell motility is involved in these processes. In 1998, we identified
      overexpression of the actin-bundling protein actinin-4 in several types of
      cancer. Protein expression of actinin-4 is closely associated with the invasive
      phenotypes of cancers. Actinin-4 is predominantly expressed in the cellular
      protrusions that stimulate the invasive phenotype in cancer cells and is
      essential for formation of cellular protrusions such as filopodia and
      lamellipodia. ACTN4 (gene name encoding actinin-4 protein) is located on human
      chromosome 19q. ACTN4 amplification is frequently observed in patients with
      carcinomas of the pancreas, ovary, lung, and salivary gland, and patients with
      ACTN4 amplifications have worse outcomes than patients without amplification. In
      addition, nuclear distribution of actinin-4 is frequently observed in small cell
      lung, breast, and ovarian cancer. Actinin-4, when expressed in cancer cell
      nuclei, functions as a transcriptional co-activator. In this review, we summarize
      recent developments regarding the biological roles of actinin-4 in cancer
      invasion. 

PMID- 26288720
TI  - Effect of packaging materials on the chemical composition and microbiological
      quality of edible mushroom (Pleurotus ostreatus) grown on cassava peels.
AB  - Edible fungi such as mushrooms are highly perishable and deteriorate few days
      after harvest due to its high moisture content and inability to maintain their
      physiological status. In this study, the effect of packaging materials on the
      nutritional composition of mushroom cultivated from cassava peels was
      investigated. Mushroom samples were dried at 50 degrees C in a cabinet dryer for
      8 h. The dried mushroom samples packaged in four different packaging materials;
      high density polyethylene (HDPE), polypropylene (PP), laminated aluminum foil
      (LAF), high density polyethylene under vacuum (HDPEV) were stored at freezing (0
      degrees C) temperatures for 12 weeks. Samples were collected at 2-week intervals
      and analyzed for proximate composition (carbohydrate, protein, fat, fiber, ash,
      moisture), mineral content (calcium, potassium), vitamin C content, and
      microbiological qualities (total aerobic count, Pseudomonal count, Coliform
      count, Staphylococcal count, Salmonella count) using the standard laboratory
      procedures. Carbohydrate, protein, fat content of dried mushrooms packaged in
      HDPE at freezing temperature ranged from 45.2% to 53.5%, 18.0% to 20.3%, and 3.2%
      to 4.3%, while mushrooms in polypropylene ranged from 45.2% to 53.5%, 18.5% to
      20.3%, 2.6% to 4.3%. Carbohydrate, protein, fat of mushroom in LAF ranged from
      47.8% to 53.5%, 17.3% to 20.3%, and 3.3% to 4.3%, respectively, while
      carbohydrate, protein, fat of mushroom in HDPEV ranged from 51.1% to 53.5%, 19.5%
      to 20.3%, and 3.5% to 4.3%. Microbiological analysis showed that total aerobic
      count, Pseudomonal count, and Staphyloccocal count of dried mushroom ranged from
      2.3 to 3.8 log cfu/g, 0.6 to 1.1 log cfu/g, and 0.4 to 0.5 log cfu/g,
      respectively. In conclusion, dried mushroom in HDPE packaged under vacuum at
      freezing temperature retained the nutritional constituents than those packaged
      with other packaging materials. 

PMID- 26288721
TI  - Nutrients and bioactive compounds content of Baillonella toxisperma, Trichoscypha
      abut and Pentaclethra macrophylla from Cameroon.
AB  - Baillonella toxisperma, Pentaclethra macrophylla and Trichoscypha abut are
      important foods for communities living around forests in Cameroon. Information on
      the nutritional value and bioactive content of these foods is required to
      establish their contribution to the nutrition and health of the communities.
      Samples of the three foods were obtained from four villages in east and three
      villages in south Cameroon. The foods were analyzed for proximate composition,
      minerals and bioactive content using standard chemical analysis methods. T. abut
      was found to be an excellent source of bioactive compounds; flavonoids (306
      mg/100 g), polyphenols (947 mg/100 g), proanthocyanins (61.2 mg/100 g), vitamin C
      (80.05 mg/100 g), and total oxalates (0.6 mg/100 g). P. macrophylla was found to
      be a rich source of total fat (38.71%), protein (15.82%) and total fiber (17.10%)
      and some bioactive compounds; vitamin E (19.4 mg/100 g) and proanthocyanins (65.0
      mg/100 g). B. toxisperma, was found to have high content of carbohydrates
      (89.6%), potassium (27.5 mg/100 g) and calcium (37.5 mg/100 g). Flavonoids,
      polyphenols, vitamins C and E are the main bioactive compounds in these forest
      foods. The daily consumption of some of these fruits may coffer protection
      against some ailments and oxidative stress. Approximately 200 g of either B.
      toxisperma or P. macrophylla, can supply 100% iron and zinc RDAs for children
      aged 1-3 years, while 300 g of the two forest foods can supply about 85% iron and
      zinc RDAs for non-pregnant non-lactating women. The three foods provide 100%
      daily vitamins C and E requirements for both adults and children. The results of
      this study show that Baillonella toxisperma, Pentaclethra macrophylla and
      Trichoscypha abut can considerably contribute towards the human nutrient
      requirements. These forest foods also contain substantial levels of health
      promoting phytochemicals notably flavonoids, polyphenols, vitamins C and E. These
      foods therefore have potential to promote nutrition and health, especially among
      forest dependent communities who consume them in substantial amounts. 

PMID- 26288719
TI  - In vitro evaluation of digestive and endolysosomal enzymes to cleave CML-modified
      Ara h 1 peptides.
AB  - Ara h 1 is a major peanut allergen. Processing-induced modifications may modulate
      the allergenic potency of Ara h 1. Carboxymethyl lysine (CML) modifications are a
      commonly described nonenzymatic modification on food proteins. In the current
      study, we tested the ability of digestive and endolysosomal proteases to cleave
      CML-modified and unmodified Ara h 1 peptides. Mass spectrometric analyses of the
      digested peptides demonstrate that carboxymethylation of lysine residues renders
      these peptides refractory to trypsin digestion. We did not detect observable
      differences in the simulated gastric fluid or endolysosomal digestion between the
      parental and CML-modified peptides. One of the tested peptides contains a lysine
      residue previously shown to be CML modified laying in a previously mapped linear
      IgE epitope, but we did not observe a difference in IgE binding between the
      modified and parental peptides. Our findings suggest a molecular mechanism for
      the increased resistance of peanut allergens modified by thermal processing, such
      as Ara h 1, to digestion in intestinal fluid after heating and could help explain
      how food processing-induced modifications may lead to more potent food allergens
      by acting to protect intact IgE epitopes from digestion by proteases targeting
      lysine residues. 

PMID- 26288722
TI  - Study on the extraction and purification of glycoprotein from the yellow
      seahorse, Hippocampus kuda Bleeker.
AB  - The optimum parameters of extraction for glycoprotein from seahorse were examined
      and determined by Box-Behnken combined with ultrasonic extraction technology.
      Column chromatography of glycoprotein was used for further purification. The
      optimal extraction conditions of seahorse glycoprotein were extracting time 4.3
      h, salt concentration 0.08 mol/L, extracting temperature 73 degrees C, raw
      material, and water ratio 1:6. At the optimal conditions, the yield of saccharide
      reached to 1.123%, and the yield of protein reached to 5.898%. For purifying the
      crude glycoprotein, the stage renounces of DEAE-52 column chromatography were
      done, respectively, with 0.05, 0.1, 0.5 mol/L NaHCO3 solution, and further
      purification was done with Sephadex G-100 column chromatography. Finally, two
      pieces of seahorse glycoprotein were obtained by the column chromatography, that
      is, HG-11 and HG-21. The saccharide content was 56.7975% and 39.479%, the protein
      content was 30.5475% and 51.747%, respectively. 

PMID- 26288723
TI  - Physico-chemical properties of instant ogbono (Irvingia gabonensis) mix powder.
AB  - The main objective of the research is to develop a recipe of instant dry soup mix
      for easy preparation of ogbono soup. Instant ogbono mix powder was processed
      using common locally ingredients. Dika kernel powder, dried ugwu leaf, crayfish,
      stock fish, and a mixture of locust bean, onion, seasoning and Cameroon powder
      were formulated at different ratios to find the best acceptable ogbono mix
      powder. The samples were subjected to proximate, functional, vitamin, mineral,
      and sensory analyses. The formulated sample D with the highest ratio of crayfish
      and stock fish had the highest value of protein and carbohydrate (24.13 and
      35.61%, respectively). The control sample (100% dika kernel powder) was low in
      moisture content (6.20%) but high in crude fat, other samples followed in this
      order (control > A > B > C > D) for crude fat. Ash, crude fiber, and carbohydrate
      showed a significant difference (P < 0.05) in all the samples. The functional
      properties of the sample showed a significant difference (P < 0.05) in all the
      samples with the control having the highest value for the water absorption,
      swelling capacity, and bulk density which may be due to the high crude fiber and
      low moisture content recorded for the control sample in the proximate analysis.
      The mineral content of all the samples were higher than the control with
      phosphorous having the highest value and iron the least value. Vitamin C was the
      main dominating vitamin in the sample followed by vitamin B2, vitamin A, and
      vitamin B3. The sensory evaluation revealed that 100% dika kernel powder gave a
      good attribute of the soup but with less nutritional composition, while some
      formulated samples showed a similar attribute with higher nutritional value.
      Sample A with the highest overall acceptability had the best attribute of ogbono
      soup. Instant ogbono mix powder has higher nutritional value and easy to cook. 

PMID- 26288724
TI  - Protecting soymilk flavor and nutrients from photodegradation.
AB  - Five different packaging treatments were studied over a 36-day period to
      determine if they protected soymilk from photo-oxidation. Soymilk was packaged in
      high-density polyethylene (HDPE) bottles with and without light protective
      additives (LPA). Two controls [(1) no LPA (translucent appearance); (2) a light
      protected control (foil overwrap over no LPA control)] and three LPA-containing
      treatments, Low (0.6% TiO2), Medium (1.3% TiO2), High (4.3% TiO2) were studied.
      Bottles were stored in a lighted refrigerated display case (average light
      intensity between 800 to 2200 lux; 3 degrees C) for 36 days and evaluated weekly.
      Soymilk packaged in high LPA bottles was protected from developing light-oxidized
      off-flavors and odors for a minimum of 15 days. High LPA bottles provided
      protection for riboflavin and controlled development of photooxidative products
      for approximately 29 days. 

PMID- 26288725
TI  - Effect of nano-composite and Thyme oil (Tymus Vulgaris L) coating on fruit
      quality of sweet cherry (Takdaneh Cv) during storage period.
AB  - Sweet cherry is one of the most appreciated fruit by consumers since it is an
      early season fruit and has an excellent quality. In this study effect of active
      nano composite formed from chitosan (as a matrix material), nano cellulose fiber
      (1% concentration) and Thyme oils (Tymus Vulgaris L) at 1% concentration on
      fruits quality was investigated. Treated fruits were stored at 1 degrees C for 5
      weeks and changes of different qualities attributes including weight loss, total
      acidity, TSS, anthocyanin, total sugar and malic acid content (by high
      performance liquid chromatography (HPLC) method) were measured each week. Results
      showed that nano composite and Thyme oil significantly affect fruit's water
      retention and so decrease fruit weight loss and preserve anthocyanin (P < 0.05).
      None of applied treatments had any significant effects in comparison with control
      in regard to acidity while total sugar content and TSS significantly affected by
      treatment compared to control samples. Result of HPLC analysis showed that there
      was no significant difference between different treatment and control sample in
      term of malic acid concentrations during storage period but increase storage time
      lead to increase malic acid concentration in all treatments. For conclusion it
      can be Saied that fruits coating with nano-composite, lead to increase fruit
      shelf life, better appearance and prevents fungal growth that may be due to
      creation of an active packaging by these compounds. 

PMID- 26288726
TI  - Effect of methyl cellulose coating on physicochemical properties, porosity, and
      surface diameter of pistachio hull.
AB  - Pistachio is a nut with high consumption that can be affected by aflatoxin
      contamination. Regarding influence of this fungus on global trade, broad studies
      in this area seem to be necessary. In this research, pistachio nuts were coated
      with methyl cellulose at different concentrations of 0.1%, 0.5%, 1%, and 2% by
      immersion method. Samples were stored in an incubator (25 degrees C) for 4
      months. Imaging was performed by electron microscope using SEM method and
      chemical changes (moisture, iodine, peroxide, and acidic value) were investigated
      during storage periods. Results showed that variations in storage time and methyl
      cellulose concentration had significant effect on moisture content and peroxide
      value (P < 0.05). Also, in case of acidic value, a significant difference was
      observed between treatments so that pistachio at concentration of 2% showed the
      highest acidic value. The highest iodine value loss was related to a
      concentration of 0.1% and the lowest value was observed in the control sample. 

PMID- 26288728
TI  - Role of HLA typing on Crohn's disease pathogenesis.
AB  - Crohn's disease (CD) is the main type of chronic inflammatory bowel disease of
      unknown etiology. Evidence from family and twin studies suggests that genetics
      plays a significant role in predisposing an individual to develop Crohn's
      disease. A susceptibility locus for Crohn's disease has been mapped 3 to
      chromosome 16: a frameshift variant and two missense variants of NOD2, encoding a
      member of the Apaf-1/Ced-4 superfamily of apoptosis regulators which is expressed
      in hematopoietic compartment cells and intestinal epithelial cells as well as in
      paneth cells, where NOD2 may play an important role in the pathogenesis of Crohn
      disease in the gastrointestinal system. This leads to alteration the structure of
      either the leucine-rich repeat domain of the protein or the adjacent region. NOD2
      activates nuclear factor NF-kB; this activating function is regulated by the
      carboxy-terminal leucine-rich repeat domain, which has two functions, first an
      inhibitory role and also acts as an intracellular receptor for components of
      microbial pathogens. Thus, NOD2 gene product confers susceptibility to Crohn's
      disease by altering the recognition of these components and/or by over-activating
      NF-kB in intestinal epithelial cells as well as in paneth cells. Further
      confirmation of a genetic predisposition comes from studies of the association
      between the human leukocyte antigen (HLA) system and CD. The immunogenetic
      predisposition may be considered an important requirement for the development of
      CD, as several alleles of human major histocompatibility complex had an
      association with CD. Although it is difficult to estimate the importance of this
      region in determining overall genetic susceptibility in a population, studies of
      HLA allele sharing within families suggest that this region contributes between
      10% and 33% of the total genetic risk of Crohn's disease. 

PMID- 26288729
TI  - Severe cardiac trauma or myocardial ischemia? Pitfalls of polytrauma treatment in
      patients with ST-elevation after blunt chest trauma.
AB  - INTRODUCTION: Thoracic injuries are the third most common injuries in polytrauma
      patients. The mechanism of injury and the clinical presentation are crucially
      important for adequate emergency treatment. PRESENTATION OF CASE: Here we present
      a case of a 37-year-old male who was admitted to our level-1 trauma center after
      motor vehicle accident. The emergency physician on scene presented the patient
      with a myocardial infarction. During initial clinical trauma assessment the
      patient developed circulatory insufficiency so that cardiopulmonary resuscitation
      was necessary. Considering the preclinical and clinical course it was decided to
      proceed with thrombolysis. Despite consistently sufficient resuscitation measures
      circulatory function was not restored and the patient remained in asystole and
      passed away. DISCUSSION: The initial assessment showed cardiopulmonary
      instability. After applying thrombolysis a therapeutic point of no return was
      reached because surgical intervention was impossible but autopsy findings showed
      severe myocardial and pulmonary contusions likely due to shear forces.
      CONCLUSION: This case outlines the importance of understanding the key mechanism
      of injury and the importance of communication at each stage of healthcare
      transfer. A transesophageal echocardiography can help to identify injuries after
      myocardial contusion.

PMID- 26288730
TI  - Intravenous immunoglobulin in necrotizing fasciitis - A case report and review of
      recent literature.
AB  - INTRODUCTION: Necrotizing fasciitis (NF) is an inflammatory disease of the soft
      tissue, which causes local tissue destruction and can lead to lethal septic
      shock. The therapy consists of early surgical treatment of the septic focus and
      an accompanying broad spectrum antibiotic therapy. Recent literature considers
      the additional use of immunoglobulin therapy in severe soft skin and tissue
      infections. PRESENTATION OF CASE: In this report, we describe the case of a 33
      year-old male patient treated at a university hospital intensive care unit
      because of an NF of his left leg. The patient rapidly developed a complicated
      septic disease after a minor superficial trauma. Despite intense microbiological
      diagnosis, no causative pathogens were identified. After non-responding to
      established broad anti-infective treatment, the patient received intravenous
      immunoglobulin, that rapidly improved his clinical condition. DISCUSSION: NF
      represents a disease processes, which is characterized by fulminant, widespread
      necrosis of soft tissue, systemic toxicity, and high mortality (>30%). Beside the
      surgical debridement and broad spectrum antibiotic therapy IVIg therapy might be
      an additional option in the treatment of NF. But the current literature
      supporting the use of IVIG in NF is largely based on retrospective or case
      controlled studies, and only small randomized trials. CONCLUSION: The
      demonstrated case suggests that IVIg treatment of patients with NF can be
      considered in case of hemodynamic unstable, critically ill patients. Although
      randomized controlled trials are missing, some patients might benefit from
      diminishing hyperinflammation by immunoglobins.

PMID- 26288731
TI  - Management of intestinal obstruction in advanced malignancy.
AB  - Patients with incurable, advanced abdominal or pelvic malignancy often present to
      acute surgical departments with symptoms and signs of intestinal obstruction. It
      is rare for bowel strangulation to occur in these presentations, and spontaneous
      resolution often occurs, so the luxury of time should be afforded while decisions
      are made regarding surgery. Cross-sectional imaging is valuable in determining
      the underlying mechanism and pathology. The majority of these patients will not
      be suitable for an operation, and will be best managed in conjunction with a
      palliative medicine team. Surgeons require a good working knowledge of the
      mechanisms of action of anti-emetics, anti-secretories and analgesics to tailor
      early management to individual patients, while decisions regarding potential
      surgery are made. Deciding if and when to perform operative intervention in this
      group is complex, and fraught with both technical and emotional challenges.
      Surgery in this group is highly morbid, with no current evidence available
      concerning quality of life following surgery. The limited evidence concerning
      operative strategy suggests that resection and primary anastomosis results in
      improved survival, over bypass or stoma formation. Realistic prognostication and
      involvement of the patient, care-givers and the multidisciplinary team in
      treatment decisions is mandatory if optimum outcomes are to be achieved. 

PMID- 26288732
TI  - Complex ventral hernia repair with a human acellular dermal matrix and component
      separation: A case series.
AB  - We present a case series of 19 patients requiring complex abdominal hernia
      repairs. Patients presented with challenging clinical histories with 95% having
      multiple significant comorbidities including overweight or obesity (84%),
      hypertension (53%), diabetes (42%), cancer (26%), and pulmonary disease (16%).
      The majority of patients (68%) had prior abdominal infections and 53% had at
      least one failed prior hernia repair. Upon examination, fascial defects averaged
      282 cm(2). Anterior and posterior component separation was performed with
      placement of a human acellular dermal mesh. Midline abdominal closure under
      minimal tension was achieved primarily in all cases. Post-operative complications
      included 2 adverse events (11%) - one pulmonary embolism and one post-operative
      hemorrhage requiring transfusion; 6 wound-related complications (32%), 1 seroma
      (5%) and 1 patient with post-operative ileus (5%). Operative intervention was not
      required in any of the cases and most patients made an uneventful recovery.
      Increased patient age and longer OR time were independently predictive of early
      post-operative complications. At a median 2-year follow-up, three patients had a
      documented hernia recurrence (16%) and one patient was deceased due to unrelated
      causes. CONCLUSION: Patients at high risk for post-operative events due to
      comorbidities, prior abdominal infection and failed mesh repairs do well
      following component separation reinforced with a human bioprosthetic mesh.
      Anticipated post-operative complications were managed conservatively and at a
      median 2-year follow-up, a low rate of hernia recurrence was observed with this
      approach.

PMID- 26288733
TI  - Recent advances in immunotherapy and vaccine development for peanut allergy.
AB  - Peanut allergy is a common problem and can be the cause of severe, life
      threatening allergic reactions. It rarely resolves, with the majority of patients
      carrying the disease onto adulthood. Peanut allergy poses a significant burden on
      the quality of life of sufferers and their families, which results mainly from
      the fear of accidental peanut ingestion, but is also due to dietary and social
      restrictions. Current standard management involves avoidance, patient education
      and provision of emergency medication, for use in allergic reactions, when they
      occur. Efforts have been made to develop a vaccine for peanut allergy. Recent
      developments have also highlighted the use of immunotherapy, which has shown
      promise as an active form of treatment and may present a disease-modifying
      therapy for peanut allergy. So far, results, especially from oral immunotherapy
      studies, have shown good efficacy in achieving desensitization to peanut with a
      good safety profile. However, the capacity to induce long-term tolerance has not
      been demonstrated conclusively yet and larger, phase III studies are required to
      further investigate safety and efficacy of this intervention. Peanut
      immunotherapy is not currently recommended for routine clinical use or outside
      specialist allergy units. 

PMID- 26288734
TI  - Recent advances in the development of vaccines for tuberculosis.
AB  - Tuberculosis (Tb) continues to be a dreadful infection worldwide with nearly 1.5
      million deaths in 2013. Furthermore multi/extensively drug-resistant Tb (MDR/XDR
      Tb) worsens the condition. Recently approved anti-Tb drugs (bedaquiline and
      delamanid) have the potential to induce arrhythmia and are recommended in
      patients with MDR-Tb when other alternatives fail. The goal of elimination of Tb
      by 2050 will not be achieved without an effective new vaccine. The recent
      advancement in the development of Tb vaccines is the keen focus of this review.
      To date, Bacille Calmette Guerin (BCG) is the only licensed Tb vaccine in use,
      however its efficacy in pulmonary Tb is variable in adolescents and adults. There
      are nearly 15 vaccine candidates in various phases of clinical trials, includes
      five protein or adjuvant vaccines, four viral-vectored vaccines, three
      mycobacterial whole cell or extract vaccines, and one each of the recombinant
      live and the attenuated Mycobacterium tuberculosis (Mtb) vaccine. 

PMID- 26288736
TI  - Immune monitoring technology primer: Single Cell Network Profiling (SCNP).

PMID- 26288735
TI  - Group B Streptococcus vaccine: state of the art.
AB  - Group B Streptococcus (GBS) is cause of neonatal invasive diseases as well as of
      severe infections in the elderly and immune-compromised patients. Despite
      significant advances in the prevention and treatment of neonatal disease, sepsis
      and meningitis caused by GBS still represent a significant public health care
      concern globally and additional prevention and therapeutic strategies against
      infection are highly desirable. The introduction of national recommended
      guidelines in several countries to screen pregnant women for GBS carriage and the
      use of antibiotics during delivery significantly reduced disease occurring within
      the first hours of life (early-onset disease), but it has had no effect on the
      late-onset diseases occurring after the first week and is not feasible in most
      countries. Availability of an effective vaccine against GBS would provide an
      effective means of controlling GBS disease. This review provides an overview of
      the burden of invasive disease caused by GBS in infants and adults, and
      highlights the strategies for the development of an effective vaccine against GBS
      infections. 

PMID- 26288737
TI  - Pembrolizumab.
AB  - The development of the cytotoxic T-lymphocyte-associated protein 4 inhibitor
      ipilimumab and its approval in 2011 for the treatment of metastatic melanoma has
      heralded a new era in immuno-oncology. Subsequently, novel agents against the
      programmed death receptor 1 (PD-1)/programmed death receptor ligand 1 (PD-L1)
      axis have shown significant activity in melanoma and a variety of other tumor
      types. Pembrolizumab was the first anti-PD-1 antibody to be approved by the US
      Food and Drug Administration for the treatment of patients with unresectable or
      metastatic melanoma with disease progression following ipilimumab, and if BRAF
      (V600) mutation positive, a BRAF inhibitor. Pembrolizumab has also received
      breakthrough status for the treatment of EGFR mutation-negative, ALK
      rearrangement-negative non-small cell lung cancer (NSCLC) that has progressed on
      or following platinum-based chemotherapy. There remain a number of pivotal trials
      in progress to further evaluate the optimal use of pembrolizumab alone and in
      combination for melanoma, NSCLC, and other tumor types. In this article, we
      review the efficacy and toxicity profile of pembrolizumab and evaluate its future
      development. 

PMID- 26288738
TI  - Influence of cardiovascular risk factors on infarct size and interaction with
      mechanical ischaemic postconditioning in ST-elevation myocardial infarction.
AB  - OBJECTIVE: Previous studies have shown that mechanical postconditioning (PostC)
      significantly reduces infarct size (IS) in patients with acute myocardial
      infarction. Our objective was to assess the influence of traditional
      cardiovascular (CV) risk factors on IS and their interaction with ischaemic PostC
      in patients with acute ST-elevation myocardial infarction (STEMI). METHODS: The
      study population was constituted from the clinical database pooling of four
      previously published PostC prospective, multicentre, randomised, open-label
      controlled trials with identical inclusion criteria. Patients with STEMI,
      presenting within 12 h of symptoms onset referred for percutaneous coronary
      intervention, were included. Mechanical ischaemic PostC was performed by four
      repeated cycles of inflation-deflation of the angioplasty balloon within 1 min of
      reflow, while the control group underwent no intervention. IS was assessed by
      measuring total creatine kinase release over 72 h. RESULTS: 173 patients, aged
      58+/-12 years, 76% males, 48% anterior infarct were included (82 in the PostC
      group, 91 in the control group). IS was significantly reduced in the PostC
      compared to the control group (71.7+/-41.6 vs 88.2+/-54.5*10(3) arbitrary units;
      p=0.027). After adjustment for abnormally contracting segments, older patients
      had smaller IS and smokers had larger IS. Gender, diabetes, hypertension,
      dyslipidemia and obesity did not have any significant effect on IS. Multivariate
      regression analysis showed that none of the traditional risk factors had a
      significant impact on the cardioprotective effect of mechanical ischaemic PostC.
      CONCLUSIONS: The present analysis suggests that the cardioprotective effect of
      mechanical PostC is not influenced by traditional CV risk factors that are
      prevalent in patients with STEMI.

PMID- 26288739
TI  - Natriuretic peptides for the detection of paroxysmal atrial fibrillation.
AB  - BACKGROUND AND PURPOSE: Silent atrial fibrillation (AF) and tachycardia (AT) are
      considered precursors of ischaemic stroke. Therefore, detection of paroxysmal
      atrial rhythm disorders is highly relevant, but is clinically challenging. We
      aimed to evaluate the diagnostic value of natriuretic peptide levels in the
      detection of paroxysmal AT/AF in a pilot study. METHODS: Natriuretic peptide
      levels were analysed in two independent patient cohorts (162 patients with
      arterial hypertension or other cardiovascular risk factors and 82 patients with
      retinal vessel disease). N-terminal-pro-brain natriuretic peptide (NT-proBNP) and
      BNP were measured before the start of a 7-day Holter monitoring period carefully
      screened for AT/AF. RESULTS: 244 patients were included; 16 had paroxysmal AT/AF.
      After excluding patients with a history of AT/AF (n=5), 14 patients had newly
      diagnosed AT/AF (5.8%) NT-proBNP and BNP levels were higher in patients with
      paroxysmal AT/AF in both cohorts: (1) 154.4 (IQR 41.7; 303.6) versus 52.8 (30.4;
      178.0) pg/mL and 70.0 (31.9; 142.4) versus 43.9 (16.3; 95.2) and (2) 216.9
      (201.4; 277.1) versus 90.8 (42.3-141.7) and 96.0 (54.7; 108.2) versus 29.1 (12.0;
      58.1). For the detection of AT/AF episodes, NT-proBNP and BNP had an area under
      the curve in receiver operating characteristic analysis of 0.76 (95% CI, 0.64 to
      0.88; p=0.002) and 0.75 (0.61 to 0.89; p=0.004), respectively. CONCLUSIONS: NT
      proBNP and BNP levels are elevated in patients with silent AT/AF as compared with
      sinus rhythm. Thus, screening for undiagnosed paroxysmal AF using natriuretic
      peptide level initiated Holter monitoring may be a useful strategy in prevention
      of stroke or systemic embolism.

PMID- 26288740
TI  - Randomised comparison of zofenopril and ramipril plus acetylsalicylic acid in
      postmyocardial infarction patients with left ventricular systolic dysfunction: a
      post hoc analysis of the SMILE-4 Study in patients according to levels of left
      ventricular ejection fraction at entry.
AB  - OBJECTIVE: Conflicting evidence exists on the benefits of treating patients with
      coronary artery disease and preserved left ventricular ejection fraction (LVEF)
      with an ACE inhibitor. This retrospective analysis of the SMILE-4 Study sought to
      compare the efficacy of zofenopril 60 mg plus acetylsalicylic acid (ASA) versus
      ramipril 10 mg plus ASA 100 mg in patients with acute myocardial infarction (AMI)
      and heart failure, according to an impaired or preserved LVEF. METHODS: The
      primary study end point was 1-year combined occurrence of death or
      hospitalisation for cardiovascular causes. A preserved LVEF was defined by a
      baseline LVEF >40% and an impaired one by an LVEF <=40%. RESULTS: 448 patients
      (63%) had preserved and 262 (37%) had impaired LVEF. The primary end point
      occurred in 125 patients with preserved (28%) and 106 patients with impaired LVEF
      (41%, p=0.001). In the first group, the rate of major cardiovascular events was
      significantly lower under zofenopril than under ramipril (23% vs 33%; OR and 95%
      CI 0.60, 0.39 to 0.91; p=0.016). This was also the case for patients with
      impaired LVEF, though between-group difference was not statistically significant
      (38% zofenopril vs 44% ramipril; OR 0.77, 0.47 to 1.26; p=0.297). LVEF values
      significantly (p<0.0001) increased during the follow-up in both subsets with no
      between-treatment differences. However, improvement rates in LVEF (increase >=5%)
      were higher in patients with impaired LVEF (72% vs 61%, p=0.006). CONCLUSIONS: In
      the SMILE-4 Study, the cardiovascular outcome of patients with post-AMI with
      preserved LVEF was more favourable in the zofenopril than in the ramipril
      treatment group. TRIAL REGISTRATION NUMBER: EudraCT Number: 2004-001150-88
      (http://www.clinicaltrialsregister.eu); Italian Ministry of Health Code:
      GUIDOTT_III_2004_001 (https://oss-sper-clin.agenziafarmaco.it).

PMID- 26288741
TI  - In vitro flubendazole-induced damage to vital tissues in adult females of the
      filarial nematode Brugia malayi.
AB  - The use of a microfilaricidal drug for the control of onchocerciasis and
      lymphatic filariasis necessitates prolonged yearly dosing. Prospects for
      elimination or eradication of these diseases would be enhanced by availability of
      a macrofilaricidal drug. Flubendazole (FLBZ), a benzimidazole anthelmintic, is an
      appealing candidate macrofilaricide. FLBZ has demonstrated profound and potent
      macrofilaricidal effects in a number of experimental filarial rodent models and
      one human trial. Unfortunately, FLBZ was deemed unsatisfactory for use in mass
      drug administration (MDA) campaigns due to its markedly limited oral
      bioavailability. However, a new formulation that provided sufficient
      bioavailability following oral administration could render FLBZ an effective
      treatment for onchocerciasis and LF. This study characterized the effects of FLBZ
      and its reduced metabolite (FLBZ-R) on filarial nematodes in vitro to determine
      the exposure profile which results in demonstrable damage. Adult female Brugia
      malayi were exposed to varying concentrations of FLBZ or FLBZ-R (100 nM-10 MUM)
      for up to five days, after which worms were fixed for histology. Morphological
      damage following exposure to FLBZ was observed prominently in the hypodermis and
      developing embryos at concentrations as low as 100 nM following 24 h exposure.
      The results indicate that damage to tissues required for reproduction and
      survival can be achieved at pharmacologically relevant concentrations. 

PMID- 26288742
TI  - Viability of developmental stages of Schistosoma mansoni quantified with
      xCELLigence worm real-time motility assay (xWORM).
AB  - Infection with helminth parasites causes morbidity and mortality in billions of
      people and livestock worldwide. Where anthelmintic drugs are available, drug
      resistance is a major problem in livestock parasites, and a looming threat to
      public health. Monitoring the efficacy of these medicines and screening for new
      drugs has been hindered by the lack of objective, high-throughput approaches.
      Several cell monitoring technologies have been adapted for parasitic worms,
      including video-, fluorescence-, metabolism enzyme- and impedance-based tools
      that minimize the screening bottleneck. Using the xCELLigence impedance-based
      system we previously developed a motility-viability assay that is applicable for
      a range of helminth parasites. Here we have improved substantially the assay by
      using diverse frequency settings, and have named it the xCELLigence worm real
      time motility assay (xWORM). By utilizing strictly standardized mean difference
      analysis we compared the xWORM output measured with 10, 25 and 50 kHz frequencies
      to quantify the motility of schistosome adults (human blood flukes) and hatching
      of schistosome eggs. Furthermore, we have described a novel application of xWORM
      to monitor movement of schistosome cercariae, the developmental stage that is
      infectious to humans. For all three stages, 25 kHz was either optimal or near
      optimal for monitoring and quantifying schistosome motility. These improvements
      in methodology sensitivity should enhance the capacity to screen small compound
      libraries for new drugs both for schistosomes and other helminth pathogens at
      large. 

PMID- 26288743
TI  - The effect of antibiotic exposure on eicosanoid generation from arachidonic acid
      and gene expression in a primitive chordate, Branchiostoma belcheri.
AB  - Chloramphenicol (Chl) is an effective antimicrobial agent widely used in
      veterinary medicine and commonly used in fish. Its use is restricted in the
      clinic because of adverse effects on the immune system and oxidative stress in
      mammals. However, the effects of Chl treatment on invertebrates remain unclear.
      Amphioxus, a basal chordate, is an ideal model to study the origin and evolution
      of the vertebrate immune system as it has a primary vertebrate-like arachidonic
      acid (AA) metabolic system. Here, we combined transcriptomic and lipidomic
      approaches to investigate the immune system and observe the oxygenated
      metabolites of AA to address the antibiotic effects on amphioxus. Tissue necrosis
      of the gill slits occurred in the Chl-treated amphioxus, but fewer epithelial
      cells were lost when treated with both Chl and ampicillin (Amp). The immune
      related pathways were dysregulated in both of the antibiotic treatment groups.
      The Chl alone treatment resulted in immunosuppression with down-regulation of the
      innate immune genes. In contrast, the Chl + Amp treatment resulted in
      immunostimulation to some extent, as shown by KEGG clustering. Furthermore, Chl
      induced a 3-fold reduction in the level of the eicosanoids, while the Chl + Amp
      treatment resulted in 1.7-fold increase of eicosanoid level. Thus in amphioxus,
      Amp might relieve the effects of the Chl-induced immune suppression and increase
      the level of eicosanoids from AA. Finally, the oxygenated metabolites from AA
      might be crucial to evaluate the effects of Chl treatment in animals. 

PMID- 26288744
TI  - Mutational analysis of the Notch2 negative regulatory region identifies key
      structural elements for mechanical stability.
AB  - The Notch signalling pathway is fundamental to cell differentiation in developing
      and self-renewing tissues. Notch is activated upon ligand-induced conformational
      change of the Notch negative regulatory region (NRR), unmasking a key proteolytic
      site (S2) and facilitating downstream events. The favoured model requires
      endocytosis of a tightly bound ligand to transmit force to the NRR region,
      sufficient to cause a structural change that exposes the S2 site. We have
      previously shown, using atomic force microscopy and molecular dynamics
      simulations, that application of force to the N-terminus of the Notch2 NRR
      facilitates metalloprotease cleavage at an early stage in the unfolding process.
      Here, mutations are made within the heterodimerization (HD) domain of the NRR
      that are known to cause constitutive activation of Notch1 whilst having no effect
      on the chemical stability of Notch2. Comparison of the mechanical stability and
      simulated forced unfolding of recombinant Notch2 NRR proteins demonstrates a
      reduced stability following mutation and identifies two critical structural
      elements of the NRR in its response to force - the linker region between Lin12
      Notch repeats LNRA and LNRB and the alpha3 helix within the HD domain - both of
      which mask the S2 cleavage site prior to Notch activation. In two mutated
      proteins, the LNRC:HD domain interaction is also reduced in stability. The
      observed changes to mechanical stability following these HD domain mutations
      highlight key regions of the Notch2 NRR that are important for mechanical, but
      not chemical, stability. This research could also help determine the fundamental
      differences in the NRRs of Notch1 and Notch2. 

PMID- 26288745
TI  - Spontaneous pneumothorax followed by reversed halo sign in immunocompromised
      patient with pulmonary mucormycosis.
AB  - Mucormycosis, an invasive fungus with a variety of clinical presentation, is a
      devastating infection in immunocompromised host. Here an unusual case of
      pulmonary mucormycosis is introduced in an immunodeficient patient in which
      pneumothorax was followed by reversed halo sign (RHS). The clinicians, who visit
      immunocompromised persons with pneumothorax, should be considerate to take
      immediate imaging and pathologic measures to confirm or reject mucormycosis. 

PMID- 26288746
TI  - Emergence of persistent Aspergillus terreus colonisation in a child with cystic
      fibrosis.

PMID- 26288747
TI  - Tinea corporis on the stump leg with Trichophyton rubrum infection.
AB  - We report a case of tinea corporis on amputated leg stump caused by Trichophyton
      rubrum. The patient, a 54-year-old male, experienced a serious traffic accident,
      resulted his right leg amputated 3 years ago. Since then prosthesis was fitted
      and protective equipment of silicone stocking was worn for the stump. He
      consulted with circular, patchy and scaly erythemas with itching on his right
      below knee amputation stump for 2 months. The diagnoses of tinea corporis on the
      stump was made based on a positive KOH direct microscopic examination,
      morphologic characteristics and sequencing of the internal transcribed spacers
      (ITS) 1 and 4, confirmed that the isolate from the scales was T. rubrum. The
      patient was cured with oral terbinafine and topical naftifine-ketaconazole cream
      following 2% ketaconazole shampoo wash for 3 weeks. Long times using prosthesis
      together with protective equipment of silicone stocking, leading to the local
      environment of airtight and humid within the prosthesis favors T. rubrum
      infection of the stump could be considered as the precipitating factors. 

PMID- 26288748
TI  - Scedosporium apiosermum infection of the "Native" valve: Fungal endocarditis in
      an orthotopic heart transplant recipient.
AB  - Scedosporium apiospermum is an increasingly appreciated pathogen in
      immunosuppressed patients. We present a case of S. apiospermum endocarditis in a
      70-year-old male who had undergone orthotopic heart transplant. Echocardiogram
      demonstrated a 1.4 cm tricuspid valve vegetation. He underwent valve replacement,
      complicated by fatal massive post-operative haemorrhage. Valve cultures grew S.
      apiospermum. To our knowledge, our case is the first reported instance of
      endocarditis caused by S. apiospermum in a recipient of a cardiac transplant. 

PMID- 26288749
TI  - Candida parapsilosis prosthetic valve endocarditis.
AB  - Candida endocarditis is a rare infection associated with high mortality and
      morbidity. There are still some controversies about Candida endocarditis
      treatment, especially about the treatment duration. We report a case of a Candida
      parapsilosis endocarditis that presented as a lower limb ischemia. The patient
      was surgically treated with a cryopreserved homograft aortic replacement. We used
      intravenous fluconazole 800 mg as initial treatment, followed with 12 months of
      400 mg fluconazole per os. The patient outcome was good. 

PMID- 26288750
TI  - Reduced neural specificity in middle-aged HIV+ women in the absence of behavioral
      deficits.
AB  - In the post combination antiretroviral therapy (cART) era, the prevalence of mild
      forms of HIV-associated neurocognitive disorders (HAND) in individuals with HIV
      infection remains high. There is a pressing need to find biomarkers that can aid
      clinical assessment of HAND, especially in those with mild or no neurocognitive
      symptoms. Here we hypothesized that a reduction in neural specificity, or the
      specificity of neuronal tuning, could serve as a potential biomarker of
      asymptomatic HAND. To directly test this hypothesis, we applied two advanced fMRI
      techniques to examine the difference in neural specificity between middle-aged
      HIV+ women and age-matched negative controls, with a focus on the fusiform face
      area (FFA), a critical region in face processing. Face discrimination performance
      was assessed outside of the scanner. While the behavioral performance of face
      discrimination was comparable between the two groups, a reduced neural
      specificity in the FFA of HIV-positive women was revealed by a novel fMRI
      analysis technique, local regional heterogeneity analysis, or Hcorr , as well as
      an established technique, fMRI-rapid adaptation. In contrast, conventional fMRI
      techniques were insensitive to these early changes. These results suggest that,
      prior to the onset of detectable behavioral deficits, significant neuronal
      dysfunctions are already present in HIV+ individuals, and these early neuronal
      dysfunctions can be detected and assessed via neural specificity, which, in
      combining with the novel Hcorr technique, has a strong potential to serve as a
      biomarker of asymptomatic HAND and other neurodegenerative diseases. 

PMID- 26288751
TI  - Altered whole-brain white matter networks in preclinical Alzheimer's disease.
AB  - Surrogates of whole-brain white matter (WM) networks reconstructed using
      diffusion tensor imaging (DTI) are novel markers of structural brain
      connectivity. Global connectivity of networks has been found impaired in clinical
      Alzheimer's disease (AD) compared to cognitively healthy aging. We hypothesized
      that network alterations are detectable already in preclinical AD and
      investigated major global WM network properties. Other structural markers of
      neurodegeneration typically affected in prodromal AD but seeming largely
      unimpaired in preclinical AD were also examined. 12 cognitively healthy elderly
      with preclinical AD as classified by florbetapir-PET (mean age 73.4 +/- 4.9) and
      31 age-matched controls without cerebral amyloidosis (mean age 73.1 +/- 6.7) from
      the ADNI were included. WM networks were reconstructed from DTI using
      tractography and graph theory. Indices of network capacity and the established
      imaging markers of neurodegeneration hippocampal volume, and cerebral glucose
      utilization as measured by fludeoxyglucose-PET were compared between the two
      groups. Additionally, we measured surrogates of global WM integrity (fractional
      anisotropy, mean diffusivity, volume). We found an increase of shortest path
      length and a decrease of global efficiency in preclinical AD. These results
      remained largely unchanged when controlling for WM integrity. In contrast,
      neither markers of neurodegeneration nor WM integrity were altered in preclinical
      AD subjects. Our results suggest an impairment of WM networks in preclinical AD
      that is detectable while other structural imaging markers do not yet indicate
      incipient neurodegeneration. Moreover, these findings are specific to WM networks
      and cannot be explained by other surrogates of global WM integrity. 

PMID- 26288752
TI  - Reduced visual cortex grey matter volume in children and adolescents with
      reactive attachment disorder.
AB  - Child maltreatment increases the risk for psychiatric disorders throughout
      childhood and into adulthood. One negative outcome of child maltreatment can be a
      disorder of emotional functioning, reactive attachment disorder (RAD), where the
      child displays wary, watchful, and emotionally withdrawn behaviours. Despite its
      clinical importance, little is known about the potential neurobiological
      consequences of RAD. The aim of this study was to elucidate whether RAD was
      associated with alterations in grey matter volume (GMV). High-resolution magnetic
      resonance imaging datasets were obtained for children and adolescents with RAD (n
      = 21; mean age = 12.76 years) and typically developing (TD) control subjects (n =
      22; mean age = 12.95 years). Using a whole-brain voxel-based morphometry
      approach, structural images were analysed controlling for age, gender, full scale
      intelligence quotient, and total brain volume. The GMV was significantly reduced
      by 20.6% in the left primary visual cortex (Brodmann area 17) of the RAD group
      compared to the TD group (p = .038, family-wise error-corrected cluster level).
      This GMV reduction was related to an internalising problem measure of the
      Strength and Difficulties Questionnaire. The visual cortex has been viewed as
      part of the neurocircuit regulating the stress response to emotional visual
      images. Combined with previous studies of adults with childhood maltreatment,
      early adverse experience (e.g. sensory deprivation) may affect the development of
      the primary visual system, reflecting in the size of the visual cortex in
      children and adolescents with RAD. These visual cortex GMV abnormalities may also
      be associated with the visual emotion regulation impairments of RAD, leading to
      an increased risk for later psychopathology. 

PMID- 26288753
TI  - Predicting the laterality of temporal lobe epilepsy from PET, MRI, and DTI: A
      multimodal study.
AB  - Pre-surgical evaluation of patients with temporal lobe epilepsy (TLE) relies on
      information obtained from multiple neuroimaging modalities. The relationship
      between modalities and their combined power in predicting the seizure focus is
      currently unknown. We investigated asymmetries from three different modalities,
      PET (glucose metabolism), MRI (cortical thickness), and diffusion tensor imaging
      (DTI; white matter anisotropy) in 28 left and 30 right TLE patients (LTLE and
      RTLE). Stepwise logistic regression models were built from each modality
      separately and from all three combined, while bootstrapped methods and split
      sample validation verified the robustness of predictions. Among all multimodal
      asymmetries, three PET asymmetries formed the best predictive model (100% success
      in full sample, >95% success in split-sample validation). The combinations of PET
      with other modalities did not perform better than PET alone. Probabilistic
      classifications were obtained for new clinical cases, which showed correct
      lateralization for 7/7 new TLE patients (100%) and for 4/5 operated patients with
      discordant or non-informative PET reports (80%). Metabolism showed closer
      relationship with white matter in LTLE and closer relationship with gray matter
      in RTLE. Our data suggest that metabolism is a powerful modality that can predict
      seizure laterality with high accuracy, and offers high value for automated
      predictive models. The side of epileptogenic focus can affect the relationship of
      metabolism with brain structure. The data and tools necessary to obtain
      classifications for new TLE patients are made publicly available. 

PMID- 26288755
TI  - Phase-based metamorphosis of diffusion lesion in relation to perfusion values in
      acute ischemic stroke.
AB  - Examining the dynamics of stroke ischemia is limited by the standard use of 2D
      volume or voxel-based analysis techniques. Recently developed spatiotemporal
      models such as the 4D metamorphosis model showed promise for capturing ischemia
      dynamics. We used a 4D metamorphosis model to evaluate acute ischemic stroke
      lesion morphology from the acute diffusion-weighted imaging (DWI) to final T2
      weighted imaging (T2-w). In 20 representative patients, we metamorphosed the
      acute lesion to subacute lesion to final infarct. From the DWI lesion deformation
      maps we identified dynamic lesion areas and examined their association with
      perfusion values inside and around the lesion edges, blinded to reperfusion
      status. We then tested the model in ten independent patients from the STroke
      Imaging Repository (STIR). Perfusion values varied widely between and within
      patients, and were similar in contracting and expanding DWI areas in many
      patients in both datasets. In 25% of patients, the perfusion values were higher
      in DWI-contracting than DWI-expanding areas. A similar wide range of perfusion
      values and ongoing expansion and contraction of the DWI lesion were seen
      subacutely. There was more DWI contraction and less expansion in patients who
      received thrombolysis, although with widely ranging perfusion values that did not
      differ. 4D metamorphosis modeling shows promise as a method to improve use of
      multimodal imaging to understand the evolution of acute ischemic tissue towards
      its fate. 

PMID- 26288756
TI  - Intractable myoclonic seizures in an allogeneic stem cell transplant recipient: A
      rare case of myoclonic epilepsy.
AB  - INTRODUCTION: Myoclonus may be a rare complication of stem cell transplant but
      has limited discussion in the scientific literature. CASE: We present a case of
      an acute myeloid leukemia survivor who developed refractory myoclonic epilepsy
      four years after graft versus host disease (GVHD) developed six days following
      matched unrelated allogeneic hematopoietic stem cell transplant. DISCUSSION:
      Graft versus host disease occurs in 30-50% of allogenic hematopoietic stem cell
      transplant patients and may cause pharmacoresistant myoclonic epilepsy; however,
      the mechanisms by which GVHD leads to recurrent myoclonic seizures are not well
      understood (Lee, 2005) [1]. The paucity of clinical reports of such manifestation
      makes it difficult to diagnose and effectively manage these patients.

PMID- 26288757
TI  - Triple pathological findings in a surgically amenable patient with mesial
      temporal lobe epilepsy.
AB  - Mesial temporal sclerosis (MTS) is a well-recognized cause of intractable
      epilepsy; however, coexistence with focal cortical dysplasia (FCD) is less
      common. Middle fossa epidermoid cysts are rare and may involve the temporal lobe.
      Most epidermoids are clinically silent, slow-growing, and seldom associated with
      overt symptomatology, including seizures. We describe a patient with multiple
      comorbidities including left MTS and a large epidermoid cyst involving the left
      quadrigeminal plate cistern compressing upon the cerebellar vermis and tail of
      the left hippocampus, resulting in refractory left temporal lobe epilepsy. The
      patient underwent left anterior temporal lobectomy. The surgical pathology
      demonstrated a third pathological finding of left temporal FCD type Ia. The
      patient has been seizure-free since the surgery. This case provides additional
      information with regard to the understanding of epileptogenicity and surgical
      planning in patients with MTS and epidermoid cysts. 

PMID- 26288754
TI  - Dynamics of the connectome in Huntington's disease: A longitudinal diffusion MRI
      study.
AB  - OBJECTIVES: To longitudinally investigate the connectome in different stages of
      Huntington's disease (HD) by applying graph theoretical analysis to diffusion MRI
      data. EXPERIMENTAL DESIGN: We constructed weighted structural networks and
      calculated their topological properties. Twenty-two premanifest (preHD), 10 early
      manifest HD and 24 healthy controls completed baseline and 2 year follow-up
      scans. We stratified the preHD group based on their predicted years to disease
      onset into a far (preHD-A) and near (preHD-B) to disease onset group. We
      collected clinical and behavioural measures per assessment time point. PRINCIPLE
      OBSERVATIONS: We found a significant reduction over time in nodal betweenness
      centrality both in the early manifest HD and preHD-B groups as compared to the
      preHD-A and control groups, suggesting a decrease of importance of specific nodes
      to overall network organization in these groups (FDR adjusted ps < 0.05).
      Additionally, we found a significant longitudinal decrease of the clustering
      coefficient in preHD when compared to healthy controls (FDR adjusted p < 0.05),
      which can be interpreted as a reduced capacity for internodal information
      processing at the local level. Furthermore, we demonstrated dynamic changes to
      hub-status loss and gain both in preHD and early manifest HD. Finally, we found
      significant cross-sectional as well as longitudinal relationships between graph
      metrics and clinical and neurocognitive measures. CONCLUSIONS: This study
      demonstrates divergent longitudinal changes to the connectome in (pre) HD
      compared to healthy controls. This provides novel insights into structural
      correlates associated with clinical and cognitive functions in HD and possible
      compensatory mechanisms at play in preHD.

PMID- 26288758
TI  - Disabling amnestic syndrome following stereotactic laser ablation of a
      hypothalamic hamartoma in a patient with a prior temporal lobectomy.
AB  - A 19-year-old man with cortical dysplasia and intractable focal seizures
      underwent a right temporal lobectomy. A hypothalamic hamartoma was subsequently
      recognized, and he then underwent MRI-guided stereotactic laser ablation.
      Unfortunately, he sustained damage to the bilateral medial mammillary bodies and
      suffered significant memory loss. We review laser ablation therapy for
      hypothalamic hamartomas and the anatomy of the memory network. We postulate that
      his persistent memory disorder resulted from a combination of the right temporal
      lobectomy and injury to the bilateral medial mammillary bodies. 

PMID- 26288760
TI  - India's draft National Health Policy, 2015: Improving policy to implementation
      effectiveness.
AB  - As the Government of India is working on drafting a new National Health Policy,
      developing national health accounts, and planning for a "health assurance
      mission," this opportunity has the potential to transform health status of
      millions of Indians and achieve universal health coverage. The draft of new
      National Health Policy of India was put in public domain for comments in early
      2015. This editorial reviews the draft National Health Policy 2015 and proposes a
      few steps to improve implementation effectiveness. 

PMID- 26288759
TI  - Structural modeling and in silico analysis of non-synonymous single nucleotide
      polymorphisms of human 3beta-hydroxysteroid dehydrogenase type 2.
AB  - Single-nucleotide polymorphisms (SNPs), a most common type of genetic mutations,
      result from single base pair alterations. Non-synonymous SNPs (nsSNP) occur in
      the coding regions of a gene and result in single amino acid substitution which
      might have the potential to affect the function as well as structure of the
      corresponding protein. In human the 3beta-hydroxysteroid
      dehydrogenases/Delta(4,5)-isomerase type 2 (HSD3B2) is an important membrane
      bound enzyme involved in the dehydrogenation and Delta(4,5)-isomerization of the
      Delta(5)-steroid precursors into their respective Delta(4)-ketosteroids in the
      biosynthesis of steroid hormones such as glucocorticoids, mineralocorticoids,
      progesterone, androgens, and estrogens in tissues such as adrenal gland, ovary,
      and testis. Most of the nsSNPs of HSD3B2 are still uncharacterized in terms of
      their disease causing potential. So, this study has been undertaken to explore
      and extend the knowledge related to the effect of nsSNPs on the stability and
      function of the HSD3B2. In this study sixteen nsSNP of HSD3B2 were subjected to
      in silico analysis using nine different algorithms: SIFT, PROVEAN, PolyPhen,
      MutPred, SNPeffect, nsSNP Analyzer, PhD SNP, stSNP, and I Mutant 2.0. The results
      obtained from the analysis revealed that the prioritization of diseases
      associated amino acid substitution as evident from possible alteration in
      structure-function relationship. Structural phylogenetic analysis using ConSurf
      revealed that the functional residues are highly conserved in human HSD3B2; and
      most of the disease associated nsSNPs are within these conserved residues.
      Structural theoritical models of HSD3B2 were created using HHPred, Phyre2 and
      RaptorX server. The predicted models were evaluated to get the best one for
      structural understanding of amino acid substitutions in three dimensional spaces.

PMID- 26288761
TI  - Women exposed to second-hand smoke more at home than at workplace: An analysis of
      GATS Report, India, 2009-10.
AB  - BACKGROUND: Tobacco smoke has adverse health effects on women of the reproductive
      age group with serious health implications for the next generation. OBJECTIVES:
      This study assessed the prevalence of current active smoking, second-hand smoke
      (SHS) exposure and the factors influencing smoke exposure in females of the
      reproductive age group. MATERIALS AND METHODS: Data from the nationally
      representative Global Adult Tobacco Survey-India (GATS 2009) was analyzed for
      socio demographic variables, tobacco-related variables and knowledge variables.
      RESULTS: 50.4% of the women in the reproductive age group had been exposed to SHS
      at home, though only 2.6% of the women were current active smokers. This was more
      than the SHS exposure at work (21.7%) and elsewhere (32.6%). SHS exposure of the
      women at home did not vary significantly with knowledge of adverse effects of
      smoking but was affected by the place of dwelling as the smoke exposure was found
      to be more among rural women. CONCLUSION: SHS exposure is more prevalent than
      current active smoking in women of the reproductive age group and that too at
      home. Thus, policies need to be framed in order to curb this menace which is a
      vicious one as women don't really have an alternative as far as this exposure is
      concerned.

PMID- 26288762
TI  - Preparedness of frontline health workers for tobacco cessation: An exploratory
      study from two states of India.
AB  - BACKGROUND: The 5As approach is a clinic-based approach and has been developed
      for primary health care providers who are uniquely positioned to interact with
      tobacco users. The 5As stands for: Ask about tobacco use at every visit, advise
      tobacco users to quit, assess readiness to quit, assist quit attempts through
      counseling and pharmacotherapy and arrange follow-up to prevent relapse. The
      present study explores whether auxiliary nurse midwives (ANMs) adhere to the 3As
      from the recommended 5As model for tobacco cessation. MATERIALS AND METHODS: The
      study was a cross-sectional study conducted among 501 ANMs in the state of
      Gujarat and Andhra Pradesh. Descriptive analysis and chi-square test were
      employed to test the differences in knowledge levels and practices of ANMs.
      Bivariate logistic regression was used to examine the association between each
      predictor variable separately and the outcome variables after adjusting for age
      and location. Data was analyzed using SPSS version 17 software. RESULTS: Majority
      of ANMs reported that they were aware of respiratory illnesses, tuberculosis,
      lung and oral cancer as conditions caused due to tobacco consumption. Awareness
      of adverse reproductive and child health effects associated with tobacco use was
      very low. Only about one third of respondents informed all patients about harmful
      effects. Only 16% of ANMs reported having ever received any on-job training
      related to tobacco control. ANMs who reported receiving training in tobacco
      control were about two times more likely to provide information on health effects
      of tobacco as compared to those who reported not being trained in tobacco control
      in the state of Gujarat. CONCLUSIONS: A majority of ANMs ask patients about
      tobacco use but provide advice only to patients suffering from specific diseases.
      A context-specific capacity building package needs to be designed to equip ANMs
      in recommended 5As approach in tobacco cessation.

PMID- 26288763
TI  - Family medicine 360 degrees : Global exchanges in family medicine.
AB  - OBJECTIVE: The global world of the 21(st) century has created communities and
      cultures that are interconnected, thanks to the development both in the field of
      transportation and technology. In this global intercultural community, future
      physicians, and even more so future general practitioners (GPs)/family physicians
      (FPs), need to be clinically competent and culturally sensitive and flexible in
      order to adapt to different social settings while delivering holistic care in
      multiethnic teams and environments with professionalism. As such, exchange
      programs are exceptional opportunities for international collaboration and the
      development of personal and professional competencies of these health care
      professionals. MATERIALS AND METHODS: This article presents a review of the
      literature on the value of exchanges as well as the results of exchange programs
      with educational content that are aimed at junior GPs/FPs. RESULTS: Exchange
      programs have been growing in popularity, especially among junior GPs/FPs. Since
      its launch in 2013, The "Family Medicine 360 degrees  (FM360 degrees ) program
      has been receiving up to 163 inquires till date, promoting global cooperation
      among the World Organization of family Doctors (WONCA)'s Young Doctors' Movementd
      (YDMs). CONCLUSIONS: By participating in an exchange program, future GPs/FPs are
      given the chance to experience intercultural communication and peer
      collaboration. They also develop personal and professional skills and thus,
      actively contribute to the growth and development of primary care all over the
      world.

PMID- 26288764
TI  - Visual dynamic e-module as a tool to fulfill informational needs and care
      continuum for diabetic patients.
AB  - INTRODUCTION: Diabetes can be envisaged as a lifelong phenomenon having the
      ominous odds for multisystemic involvement in the duration of disease. The
      probabilities of the occurrence of these events are influenced by the adopted
      lifestyle. Hence, information about the disease and lifestyle modification are
      vital from the perspective of prognostics. This study attempts to explore the
      potential of a "visual dynamic tool" for imparting knowledge and consequently
      received acumen by diabetic patients. OBJECTIVES: To appraise the effectiveness
      of a constructed visual dynamic module (encompassing the various dimensions
      related to and affected by diabetes) by capturing the opinions, perceptions, and
      experiences of the diabetic patients who underwent intervention through the
      module. MATERIALS AND METHODS: A visual e-module with dynamically imposed and
      animated images in the vernacular (Hindi) was prepared. This module was
      instituted among the diabetic patients in a logical sequence for consecutive 3
      days. All the diabetic patients who underwent this intervention were interviewed
      in depth in order to ascertain the effectiveness of the module. These interviews
      were analyzed by thematic and framework analyses. RESULT: The visual module was
      perceived by the diabetic patients as an optically engaging tool for receiving,
      connecting, and synthesizing information about diabetes. They sensed and
      expressed the ease to connect with the images and labeled the received
      information as inclusive. CONCLUSION: Initial evidences suggest that visual e
      module is an effective and efficient tool for knowledge management in diabetes.
      This issue may be further explored at diverse academic and clinical settings for
      gathering more information for efficacy.

PMID- 26288765
TI  - Health and beyond...strategies for a better India: using the "prison window" to
      reach disadvantaged groups in primary care.
AB  - As of 2013, the latest statistics available, more than 400,000 individuals are
      lodged in Indian prisons. Prisoners represent a heterogeneous population,
      belonging to socially diverse and economically disadvantaged sections of society
      with limited knowledge about health and healthy lifestyles. There is considerable
      evidence to show that prisoners in India have an increased risk of mental
      disorders including self-harm and are highly susceptible to various communicable
      diseases. Coupled together with abysmal living conditions and poor quality of
      medical services, health in prisons is a matter of immense human rights concern.
      However, the concept and the subsequent need to view prison health as an
      essential part of public health and as a strategic investment to reach persons
      and communities out of the primary health system ambit is poorly recognized in
      India. This article discusses the current status of prison healthcare in India
      and explores various potential opportunities the "prison window" provides. It
      also briefly deliberates on the various systematic barriers in the Indian prison
      health system and how these might be overcome to make primary healthcare truly
      available for all. 

PMID- 26288766
TI  - Validity, reliability, and generalizability in qualitative research.
AB  - In general practice, qualitative research contributes as significantly as
      quantitative research, in particular regarding psycho-social aspects of patient
      care, health services provision, policy setting, and health administrations. In
      contrast to quantitative research, qualitative research as a whole has been
      constantly critiqued, if not disparaged, by the lack of consensus for assessing
      its quality and robustness. This article illustrates with five published studies
      how qualitative research can impact and reshape the discipline of primary care,
      spiraling out from clinic-based health screening to community-based disease
      monitoring, evaluation of out-of-hours triage services to provincial psychiatric
      care pathways model and finally, national legislation of core measures for
      children's healthcare insurance. Fundamental concepts of validity, reliability,
      and generalizability as applicable to qualitative research are then addressed
      with an update on the current views and controversies. 

PMID- 26288767
TI  - An audit of the completion of radiology request forms and the request practice.
AB  - OBJECTIVE: To assess the degree of utilization of the radiology request form
      (RRF), the extent of completion each form, the frequency of filling the fields in
      all the forms, and its effectiveness as a communication tool between the
      referring clinicians and radiologists. MATERIALS AND METHODS: All the RRFs for
      conventional radiographic examinations were audited over a 3-month period. A
      database containing all the fields in the form, type of request paper used, and
      legibility of the physician's handwriting was created. A few resident
      radiologists in the plain film reporting unit were recruited to join in
      collecting the data daily. We used simple statistical methods to analyze the
      extent of completion of each form, frequency of completion of the fields in all
      the request forms, frequency of use of the appropriate form, and frequency of
      legibility of the physician's handwriting. The results are expressed in
      percentages. RESULTS: Five hundred eighty (580) requests were analyzed,
      consisting of 180 for males and 400 for females. The most-completed request form
      was 86.67% filled, while the least-completed was 26.67%. The most frequently
      filled field was the requested examination (99.66%). Of the clinicians, 28% did
      not use the RRF for their referrals, while 7.37% had illegible handwriting.
      CONCLUSION: A significant number of the referring clinicians did not make the
      best use of the radiology department by not using the institution's approved RRF
      as an effective means of communication with the radiologists, mainly due to the
      inadequate completion of the forms.

PMID- 26288768
TI  - Are interventions to reduce sitting at workplace effective?
AB  - It is common for family physicians in developing nations like India to encounter
      patients whose profession demands sedentary lifestyle. Such patients present with
      back problems, obesity, cardiovascular diseases and diabetes and ask doctors for
      advice on how to decrease sitting. Workplaces need to address this issue by
      inculcating strategies to decrease sitting and improve health of their employees.
      Occupational physicians too need to suggest evidence-based strategies to
      employers. This article provides an evidence based summary about what
      interventions are actually effective for decreasing sitting at workplace. 

PMID- 26288769
TI  - Can routine screening and iron supplementation for iron deficiency anemia in
      nonsymptomatic pregnant women improve maternal and infant health outcomes?
AB  - Pregnant women have an increased need for iron that might not be met with diet
      alone. Due to physiologic anemia and population differences, no set criteria for
      defining iron deficiency anemia (IDA) are available globally. Serum ferritin and
      transferrin levels are often used to guide therapy by clinicians. Studies have
      reported an association between poor iron status and negative health outcomes
      such as low birth weight, premature birth, and perinatal death for women and
      their infants, although the evidence is weak. 

PMID- 26288772
TI  - Knowledge and awareness of Consumer Protection Act among private dentists in
      Tricity, Punjab.
AB  - BACKGROUND: Consumer Protection Act (CPA) aims to protect the interests of the
      patients in case of any unethical treatment rendered by a medical or a dental
      health professional. The present study was conducted to assess knowledge and
      awareness of CPA among dental professionals in a Tricity in India. MATERIALS AND
      METHODS: A cross-sectional study was conducted among 265 private dental
      practitioners in Tricity. A close-ended self-structured questionnaire was
      administered which contained 15 questions on knowledge and awareness regarding
      CPA. Categorization of knowledge scores was done at three levels-low, medium and
      high. Statistical analysis was done using ANOVA and Student t-test. RESULTS:
      54.7% (145) of subjects were having low knowledge scores, 23.3% (62) had a medium
      score and 21.8% (58) had a high score. Mean knowledge score according to
      educational level was statistically significant (P<0.05), whereas there was no
      significant difference in case of gender and type of practice (P > 0.05).
      CONCLUSION: The results of the present study showed that majority of the subjects
      were aware of the existence of CPA but knowledge regarding basic rules and
      regulations was lacking in few studies. Therefore, dental professionals need to
      keep them updated of various rules and latest amendments to save themselves from
      any litigation.

PMID- 26288771
TI  - Low uptake of periodic health examinations in the Kingdom of Saudi Arabia, 2013.
AB  - INTRODUCTION: It is unknown whether Saudis receive health examinations
      periodically. To inform health authorities on the health-seeking behavior of the
      Saudi population, we investigated patterns of periodic health examination (PHE)
      use by Saudis. MATERIALS AND METHODS: We conducted a nationally representative
      multistage survey of individuals aged 15 years or older on sociodemographic
      characteristics, healthcare utilization, and self-reported chronic conditions. We
      used a backward elimination multivariate logistic regression model to measure
      associations between PHE and sociodemographic, behavioral, and health
      characteristics. RESULTS: Between April and June 2013, a total of 12,000
      households were contacted, and 10,735 participants completed the survey (response
      rate of 89.4%). Among participants, 2542 (22.9%), representing more than 2.7
      million Saudis aged 15 years or older, received a PHE during the past 2 years.
      Moreover, 7463 (73.5%) participants, representing 9.1 million Saudis, visited a
      healthcare setting in the past 2 years due to illness or injury. The likelihood
      of receiving a PHE in the past 2 years increased with age, education, being
      married, consumption of five servings of fruits and vegetables per day, diagnoses
      of prediabetes, diabetes, or hypercholesterolemia, and a visit to a healthcare
      setting within the last 2 years due to an illness or an injury. DISCUSSION: This
      is the first national study to investigate the use of PHE in Kingdom of Saudi
      Arabia (KSA) where healthcare is freely available. Few Saudis seek preventive
      healthcare and most healthcare visits are for injuries or sickness. KSA may
      reduce its health expenditures by routinizing PHE and detecting chronic
      conditions at early stages.

PMID- 26288770
TI  - Orofacial tuberculosis: Clinical manifestations, diagnosis and management.
AB  - Orofacial tuberculosis (TB) is an uncommon form of extrapulmonary TB and is
      nonspecific in its clinical presentation. It can be misdiagnosed especially when
      oral lesions are present before systemic symptoms become apparent. Doctors
      especially attending dentist who generally is the first among clinicians to come
      across such pathological entity should be aware of the orofacial lesions of TB
      and consider them in the differential diagnosis of suspicious oral lesions to
      ensure early diagnosis of TB and its treatment. In this review, we have discussed
      in detail the clinical presentation of various forms of orofacial TB, diagnosis,
      and management of patients. Also, an update is provided about recent anti-TB drug
      development. 

PMID- 26288773
TI  - Evaluation of input and process components of quality of child health services
      provided at 24 * 7 primary health centers of a district in Central Gujarat.
AB  - CONTEXT: With the critical Indian challenge on child survival and health, time is
      ripe to initiate focus on quality of services apart from measuring coverage, to
      bring about improvements. AIMS: To assess the quality of child health services
      provided at 24 * 7 Primary Health Centers of Vadodara District in Gujarat in
      terms of Input and Process Indicators. SETTINGS AND DESIGN: The study was carried
      out in 12 randomly chosen 24 * 7 Primary Health Centers (PHCs) of Vadodara
      district using a modified quality assessment checklist of the Program on District
      Quality Assurance for Reproductive and Child Health (RCH) services with use of
      scores from May 2010 to June 2011. SUBJECTS AND METHODS: Inputs assessment was
      done by facility survey. Process assessment for the four child health service
      components used actual observation of service, review of records and interview of
      service providers and clients. RESULTS: The mean obtained score for facilities in
      Input section was 65%. Highest score was obtained for Drugs and Consumables (86%)
      followed by Equipments and Supplies (74%). The score obtained for Infrastructure
      facility was 65%, Personnel and training was 56% and Essential protocols and
      guidelines scored 43%. The mean obtained score in the process section was 55%.
      Highest scores were obtained for immunization at 76%. This was followed by
      newborn care (52%), growth monitoring (52%). management of sick child (41%).
      CONCLUSION: Quality improvement efforts should focus not only on resource
      intensive structural improvements, but also on cost-effective measures at
      improving service delivery process, especially adherence to service guidelines by
      providers.

PMID- 26288774
TI  - Knowledge and practice of Accredited Social Health Activists for maternal
      healthcare delivery in Delhi.
AB  - INTRODUCTION: The role of community health workers in healthcare delivery system
      is considered inevitable to meet the goal of universal healthcare provision. The
      study was planned to assess the knowledge and practices for maternal health care
      delivery among Accredited Social Health Activist (ASHA) workers in North-East
      district of Delhi, India. MATERIALS AND METHODS: A descriptive cross-sectional
      study was conducted in North-East district of Delhi among 55 ASHA workers after
      taking written informed consent. Data were collected using a pretested semi
      structured questionnaire consisted of items on sociodemographic profile of ASHA
      workers, knowledge, and practices about maternal health. The data was analyzed by
      using SPSS software version 17. Qualitative data were expressed in percentages
      and quantitative data were expressed in mean +/- standard deviation (SD).
      RESULTS: Mean age (+/-SD) of ASHAs was 31.84 +/- 7.2 years. Most of the ASHAs
      workers were aware of their role in provision of maternal health services. Most
      of the ASHAs workers were aware of their work of bringing mothers for antenatal
      check-up (94.5%), counseling for family planning (96.4%), and accompanying them
      for hospital for delivery (89.1%). 87% of ASHAs knew that iron tablets have to be
      taken for minimum 100 days during pregnancy. 51 (92.7%) ASHAs reported that they
      used to maintain antenatal register. Some problems reported by ASHAs while
      working in community were shortage of staff at health center (16.4%), no
      transportation facility available (14.5%), no money for emergency, and opposition
      from local dais (12.7% each). CONCLUSION: Present study showed that ASHAs
      knowledge is good but their practices are poor due to number of problems faced by
      them which need to be addressed through skill based training in terms of good
      communication and problem solving. Monitoring should be made an integral part of
      ASHA working in the field to ensure that knowledge is converted into practices as
      well.

PMID- 26288775
TI  - Dietary pattern and nutritional deficiencies among urban adolescents.
AB  - INTRODUCTION: Adolescents are considered to be a nutritionally vulnerable segment
      of the population. There is a greater need to look into the nutritional status of
      adolescents but unfortunately, precise estimates of their dietary intake, dietary
      practices as well as nutritional deficiencies have been the least explored area.
      The general objective for conducting this study was to assess the dietary pattern
      and nutritional deficiencies among adolescents. MATERIALS AND METHODS: A cross
      sectional study was conducted among adolescents in schools and colleges in the
      urban areas of Jhansi district in Uttar Pradesh. The study sample consisted of
      400 school children in the age group of 10-19 years. Food consumption of the
      subjects was assessed using a 3-day food intake recall method. RESULTS: Mean age
      of the adolescents was 14.16 years. More than half of the children studied had
      malnutrition (53.5%). Mean intake of calorie, protein, fat, iron, and vitamins A
      and C were lower than the Recommended Dietary Allowances (RDAs). The habitual
      dietary pattern indicated poor consumption of milk, liver, and leafy vegetables.
      In comparison to boys (31.5%), more girls (46%) were underweight. On seeing the
      association, nutritional status of these adolescents within the normal limits
      were found to be significantly higher in those from nuclear families (P < 0.001),
      those with better educated parents (P < 0.000), and those from families of higher
      socioeconomic status (P < 0.000). CONCLUSION: Overall, among the participants,
      there were both macro- and micronutrients deficiencies. Therefore, there is a
      need to encourage people to adopt small family norms, and a need for the
      sensitization of both adolescents and their parents through health and nutrition
      education (HNE) to improve the health and nutritional status of the adolescents.

PMID- 26288776
TI  - Clinical and laboratory profile of dengue in the elderly.
AB  - BACKGROUND: Dengue is the most rapidly spreading mosquito-borne viral disease in
      the world with a 30-fold increase in incidence in the last 50 years.
      Approximately, 50 million dengue infections occur annually. AIM: To study the
      various clinical and laboratory manifestations of dengue in the elderly and
      observe for any variations in IgM titer elevation with progression of age.
      DESIGN: Retrospective observational study. SUBJECTS AND METHODS: Medical charts
      of all patients admitted to the Division of Geriatrics of the institute during
      study period were reviewed for collection of demographic, clinical, and
      laboratory information. The diagnosis of dengue was made based on positive dengue
      IgM ELISA. An elderly patient referred to one whose age was >=60 years. RESULTS:
      Fever and myalgia were noted to be the most common clinical manifestation with
      only four patients presenting with overt bleeding manifestations. Only one
      patient presented in delirium and there was no case fatality. Thrombocytopenia
      was the single most common hematological abnormality noted. Hyponatremia was
      found to be prevalent in a majority of the patients and were symptomatic in more
      than half of them. There have been very few studies done worldwide on the varied
      clinical manifestations of dengue in the elderly.

PMID- 26288777
TI  - Morbidity status of low birth weight babies in rural areas of Assam: A
      prospective longitudinal study.
AB  - INTRODUCTION: Low birth weight (LBW) infants suffer more episodes of common
      childhood diseases and the spells of illness are more prolonged and serious.
      Longitudinal studies are useful to observe the health and disease pattern of LBW
      babies over time. AIMS: This study was carried out in rural areas of Assam to
      assess the morbidity pattern of LBW babies during their first 6 months of life
      and to compare them with normal birth weight (NBW) counterparts. MATERIALS AND
      METHODS: Total 30 LBW babies (0-2 months) and equal numbers of NBW babies from
      three subcenters under Boko Primary Health Centre of Assam were followed up in
      monthly intervals till 6 months of age in a prospective fashion. RESULTS: More
      than two thirds of LBW babies (77%) were suffering from moderate or severe under
      nutrition during the follow up. Acute respiratory tract infection (ARI) was the
      predominant morbidity suffered by LBW infants. The other illnesses suffered by
      the LBW infants during the follow up were diarrhea, skin disorders, fever and ear
      disorders. LBW infants had more episodes of hospitalization (65%) than the NBW
      infants (35%). Incidence rate of episodes of morbidity was found to be higher
      among those LBW infants who remained underweight at 6 months of age (Incidence
      rate of 49.3 per 100 infant months) and those who were not exclusively breast fed
      till 6 months of age (Incidence rate of 66.7 per 100 infant months). CONCLUSION:
      The study revealed that during the follow up, incidence of morbidities were
      higher among the LBW babies compared to NBW babies. It was also observed that ARI
      was the predominant morbidity in the LBW infants during first 6 months of age.

PMID- 26288778
TI  - Scar formation and tuberculin conversion following BCG vaccination in infants: A
      prospective cohort study.
AB  - BACKGROUND: There is considerable variation in BCG scar failure rate on available
      data and correlation between BCG scar and tuberculin conversion remains
      controversial. Through this study we aimed to determine the scar failure rate and
      tuberculin conversion in term infants vaccinated with BCG within the first month.
      MATERIALS AND METHODS: A prospective cohort study was conducted among 85
      consecutive infants weighing >2 kg attending the immunization clinic of a medical
      college hospital. Fifteen subjects who could not complete the follow up were
      excluded. Total of 70 cases were analyzed. All babies were administered 0.1 ml of
      BCG and examined at 3 months (+1 week) for scar. Tuberculin test was done with
      5TU PPD. An induration of >5 mm was considered positive. Statistical analysis was
      done using Microsoft Excel and SPSS-22. RESULTS: Out of the 70 infants, 41
      (58.6%) were males. Although majority (72.9%) of infants were vaccinated within 7
      days, only 18 (25.7%) received BCG within 48 hours of birth. Sixty-four (91.4%)
      had a visible scar at 12 weeks post vaccination representing a scar failure rate
      of 8.6%. Tuberculin test was positive in 50 (71.4%). The mean +/- s.d. for scar
      and tuberculin skin test (TST) reaction size was 4.93 +/- 2.01 mm and 6.01 +/-
      3.22 mm, respectively. The association between scar formation and tuberculin
      positivity was highly significant (P < 0.001). There was significant correlation
      between scar size and TST size (r = 0.401, P = 0.001). CONCLUSIONS: Less than 10%
      of infants fail to develop a scar following BCG vaccination. There is good
      correlation between scar positivity and tuberculin conversion.

PMID- 26288780
TI  - Maternal and neonatal outcomes of gestational diabetes: A retrospective cohort
      study from Southern India.
AB  - BACKGROUND: The prevalence of gestational diabetes is on the rise. Understanding
      the various outcomes of it is necessary to face this challenge. OBJECTIVES: To
      study the frequency of occurrence of various maternal and fetal outcomes among
      gestational diabetes patients. METHODS: This is a retrospective cohort study
      conducted in rural Kerala, a southern state of India. The study participants were
      followed up for a period of 4 years, from 2007 to 2011. The participants included
      60 women with gestational diabetes and 120 women without gestational diabetes.
      Gestational diabetes was the major exposure variable. The frequencies of various
      outcomes were computed. Multivariable logistic regression was done to compute the
      risk for various outcomes in gestational diabetes. RESULTS: The major outcomes
      included termination of pregnancy by caesarean section, long-term progression to
      type 2 diabetes, in-born nursery (IBN) admissions and increased neonatal birth
      weight. The maximum adjusted RR [13.2 (1.5-116.03)] was for the development of
      type 2 DM later. CONCLUSION: Gestational diabetes can result in significant feto
      maternal outcomes; so better facilities are needed to manage gestational
      diabetes.

PMID- 26288779
TI  - Risk factors associated with default among tuberculosis patients in Darjeeling
      district of West Bengal, India.
AB  - BACKGROUND: The treatment outcome "default" under Revised National Tuberculosis
      Control Program (RNTCP) is a patient who after treatment initiation has
      interrupted treatment consecutively for more than 2 months. AIMS: To assess the
      timing, characteristics and distribution of the reasons for default with relation
      to some sociodemographic variables among new sputum-positive (NSP) tuberculosis
      (TB) patients in Darjeeling District, West Bengal. SETTINGS AND DESIGN: A case
      control study was conducted in three tuberculosis units (TUs) of Darjeeling from
      August'2011 to December'2011 among NSP TB patients enrolled for treatment in the
      TB register from 1(st) Qtr'09 to 2(nd) Qtr'10. Patients defaulted from treatment
      were considered as "cases" and those completed treatment as "controls" (79 cases
      and 79 controls). MATERIALS AND METHODS: The enrolled cases and controls were
      interviewed by the health workers using a predesigned structured pro-forma.
      STATISTICAL ANALYSIS USED: Logistic regression analysis, odds ratios (OR),
      adjusted odds ratios (AOR). RESULTS: 75% of the default occurred in the intensive
      phase (IP); 54.24% retrieval action was done within 1 day during IP and 75%
      within 1 week during continuation phase (CP); cent percent of the documented
      retrieval actions were undertaken by the contractual TB program staffs. Most
      commonly cited reasons for default were alcohol consumption (29.11%), adverse
      effects of drugs (25.32%), and long distance of DOT center (21.52%). In the
      logistic regression analysis, the factors independently associated were
      consumption of alcohol, inadequate knowledge about TB, inadequate patient
      provider interaction, instances of missed doses, adverse reactions of anti-TB
      drugs, Government Directly Observed Treatment (DOT) provider and smoking.
      CONCLUSIONS: Most defaults occurred in the intensive phase; pre-treatment
      counseling and initial home visit play very important role in this regard. Proper
      counseling by health care workers in patient provider meeting is needed.

PMID- 26288781
TI  - Prevalence of diabetes and pre-diabetes and assessments of their risk factors in
      urban slums of Bangalore.
AB  - BACKGROUND: To determine the prevalence of diabetes and pre-diabetes and to
      assess the risk factors associated with diabetes and pre-diabetes in the urban
      slums of Bangalore. MATERIALS AND METHODS: A cross-sectional study was conducted
      in four slums of Bangalore in the age group of 35 years and above comprising of
      total 2013 subjects. Risk factors like age, sex, family history, behavior,
      physical activity, BMI, waist hip ration, diet habits were assessed to find their
      association with diabetes. RESULTS: Prevalence of diabetes was 12.33% and of pre
      diabetes was 11.57%. Prevalence was more among the females compared to males.
      Increasing age, over weight and obesity, sedentary life style, tobacco
      consumption, diet habits showed statistically significant association with
      prevalence of diabetes and pre-diabetes. CONCLUSION: Physical activity like
      regular exercises both at the office and at home, fibers-rich diet, blood sugar
      estimation after 35 years are some of the recommendations which can control
      diabetes.

PMID- 26288782
TI  - Assessment of morbidity pattern, quality of life and awareness of government
      facilities among elderly population in South India.
AB  - BACKGROUND: This study was done to assess the determinants of morbidity pattern,
      quality of life (QoL) and awareness of elderly about various government schemes
      and social security legislations. MATERIALS AND METHODS: Data was collected by
      house to house survey among participants aged 60 years and above using a
      structured interview schedule. The QoL was assessed using Kannada version of
      WHOQOL-BREF instrument following language validation. RESULTS: Mean age of 206
      participants was 69.6+/-6.7 years. Half of them were males and majority were
      graduates 54 (26.2%). Morbidity was present among 194 (94.2%) participants (95%
      CI 89.5-98.9%), most common being hypertension 96 (46.6%). Morbid conditions were
      seen more among less educated (P = 0.007). Only 68 (33%) were under medical
      insurance coverage, 17 (8.3%) were under old age government pension and 74
      (35.9%) were under retirement pension scheme. Social relationships, psychological
      health and environmental domain scores were associated with socio-economic
      status. Social relationship domain score was significantly better among well
      educated participants and those without morbidities. Level of ambulation was
      significantly associated with QoL scores in all domains (P < 0.001). Majority of
      the participants 132 (64.1%) had moderate level of awareness about government
      facilities for senior citizens. Awareness level was significantly better among
      males (P < 0.001), well educated (P < 0.001), better socio-economic status
      respondents (P < 0.001) and those currently working (P = 0.026). CONCLUSION:
      Health status of elderly needs improvement which would also improve their QoL.
      Awareness about various government schemes needs to be enhanced to improve its
      utilization. The results of this study are expected to help policy makers in
      planning comprehensive services for elderly residing in this area.

PMID- 26288783
TI  - Prevalence and Patterns of Coexistence of Multiple Chronic Conditions: A Study
      from Indian Urban Outpatient Setting.
AB  - BACKGROUND: Chronic diseases are a common cause for seeking care in a hospital,
      however little is known about prevalence and spectrum of multiple chronic
      conditions (MCC) in Indian context. Estimates for coexistence of MCC range from
      one-fourth of all primary care attendees in Spain to two-thirds of all medicare
      attendees in the United States. This study was designed to estimate the similar
      prevalence and patterns in an Indian outpatient setting. MATERIALS AND METHODS:
      This study was performed at All India Institute of Medical Sciences Bhopal
      between May and June 2013, a hospital which had just started outpatient services
      in this period. All consecutive patients that presented to Medicine, Neurology,
      and Orthopedics clinics were sought to be included in the study, and information
      about their current diagnoses was abstracted from their outpatient records. All
      patients with one or more chronic disease diagnosis were asked about their
      monthly out-of-pocket expenditure. We performed a descriptive analysis of the
      demographic, medical diagnoses, and out-of-pocket expenditure variables. RESULTS:
      A total of 785 patients were included in the study, and 286 (36%) of them had one
      or more chronic disease diagnosis. Of these, 103 (13%) had a single chronic
      disease, while 183 (23%) had more than one chronic disease diagnosis. Among those
      with MCCs, chronic vascular diseases in combination, followed by combinations of
      chronic vascular and immunological diseases were common patterns. There was a
      significant rising trend in average out-of-pocket expenditure with increasing
      number of chronic disease diagnoses. CONCLUSION: Co-existence of multiple chronic
      diseases is common in those who seek hospital-based care. This fact has important
      implications for education and clinical decision making in primary care.

PMID- 26288784
TI  - Treatment of uncomplicated symptomatic urinary tract infections: Resistance
      patterns and misuse of antibiotics.
AB  - INTRODUCTION: Uncomplicated but symptomatic urinary tract infections (UTIs) are a
      common problem seen in practice. The study was undertaken to assess the most
      common pathogens responsible for uncomplicated symptomatic UTIs and the
      antimicrobial resistance pattern in a hospital in Bangalore. The study also
      explores the issue of antibiotic usage for these patients. MATERIALS AND METHODS:
      The study was conducted in the Medicine department of a tertiary hospital in
      Bangalore. In all, 196 patients presented with symptoms of UTI. Bacterial growth
      was determined by standard microbiology techniques on freshly voided mid-steam
      urine samples collected from recruited patients. Patients' demographic data,
      urine culture results, resistance rates to antimicrobial agents and prescribed
      empiric antimicrobial therapy were analyzed. RESULTS: The prevalence of UTI was
      32.1%; majority (67.9%) of the symptomatic did not have UTI based on culture
      report. Gram-negative bacteria constituted the largest group with a prevalence of
      84.1% (53/63), with Escherichia coli being the most common (70%) uropathogen.
      Gram-negative isolates showed high level of sensitivity to amikacin (90.6%) and
      nitrofurantoin (77.4%). Most of the gram-positive organisms were susceptible to
      nitrofurantoin (70%) and gentamicin (50%). Uropathogens isolated demonstrated
      high resistance to cotrimoxazole, fluoroquinolones, and beta-lactam antibiotics.
      It was found out that 30.1% of the patients were wrongly managed of which 14.7%
      were over treated. CONCLUSION: UTI can be over diagnosed and over treated on the
      basis of clinical signs, symptoms and urine microscopy. In the era of emerging
      anti-microbial resistance, effective counseling and delay in antibiotic
      initiation or empirical therapy with a short course of nitrofurantoin is highly
      recommended. Empirical therapy guidelines should be updated periodically to
      reflect changes in antimicrobial resistance of uropathogens.

PMID- 26288785
TI  - Clinical profile of non-traumatic acute abdominal pain presenting to an adult
      emergency department.
AB  - BACKGROUND: Abdominal pain is one of the most common reasons for presenting to
      the emergency depatment (ED) and the etiology is varied. MATERIALS AND METHODS:
      This prospective observational study was conducted in a large ED of a tertiary
      care center in India. All patients older than 15 years and presenting with non
      traumatic abdominal pain to the ED from May 2012 to October 2012 were recruited
      and the demographic characteristics, diagnosis and outcome were analyzed.
      RESULTS: The study cohort included 264 patients over a 6 month period. More than
      half (55.6%) were aged between 15 and 40 years. There was a male predominance
      (56.8%). Majority of the patients (76.9%) presented with abdominal pain of less
      than 72 hour duration. The pain was sudden in onset in 54.9% of patients. Dull
      type was the most common character of pain (36%) followed by colicky type
      (22.3%). The most common site of pain was the lower abdomen (45.8%). Upper
      abdominal pain was seen in 26.9% and the pain was generalized in 27.3% of
      patients. The common causes were uretericcolic (16.3%), urinary tract infection
      (12.5%), acute pancreatitis (11%), acute appendicitis (10.6%) and acute gastritis
      (8%). More than half (51.9%) discharged from ED and 37% of cases were managed by
      the emergency physicians. Surgical intervention was required in 25.8% of
      patients. The mortality rate was 2.3%. CONCLUSIONS: Abdominal pain is a common ED
      symptom and clinicians must consider multiple diagnoses, especially those that
      require immediate intervention to limit morbidity and mortality.

PMID- 26288786
TI  - Menstrual characteristics and prevalence of dysmenorrhea in college going girls.
AB  - BACKGROUND: Dysmenorrhea is a common gynecological condition with painful
      menstrual cramps of uterine origin. Prevalence of primary dysmenorrhea is not yet
      clearly studied in central India. OBJECTIVE: To study prevalence of primary
      dysmenorrhea in young girls and to evaluate associated clinical markers of
      dysmenorrhea. MATERIALS AND METHODS: In a cross-sectional study, data was
      collected among 310 girls (18-25 years) on age at menarche, presence and absence
      of dysmenorrhea, dysmenorrhea duration, pre-menstrual symptoms (PMS), family
      history, menses irregularities, menstrual history, severity grading using visual
      analogue scale (VAS) using a semi-structured questionnaire. RESULTS: Dysmenorrhea
      was reported in 84.2% (261) girls and 15.8% (49) reported no dysmenorrhea. Using
      VAS, 34.2% of girls experienced severe pain, 36.6% moderate and 29.2% had mild
      pain. Bleeding duration was found to be significantly associated with
      dysmenorrhea (chi(2) = 10.5; P < 0.05), girls with bleeding duration more than 5
      days had 1.9 times more chance of getting dysmenorrhea (OR: 1.9; 95% CI: 1.7-3).
      Moreover, girls with the presence of clots had 2.07 times higher chance of having
      dysmenorrhea (OR: 2.07; 95% CI: 1.04-4.1) (P < 0.05). Almost 53.7% girls who had
      some family history of dysmenorrhea, 90.9% experience the condition themselves
      (chi(2) = 11.5; P < 0.001). Girls with family history of dysmenorrhea had three
      times greater chance of having the same problem (OR: 3.0; 95% CI: 1.5-5.8; P =
      0.001). CONCLUSION: Dysmenorrhea is found to be highly prevalent among college
      going girls. Family history, bleeding duration and presence of clots were
      significant risk factors for dysmenorrhea.

PMID- 26288787
TI  - Perceptions of teachers about learning disorder in a northern city of India.
AB  - BACKGROUND: Teachers are perhaps the closest observers of child's academic
      performance and can be instrumental in detecting learning disorder (LD) early.
      OBJECTIVES: The present study aimed to assess the teachers' perceptions about LD.
      MATERIALS AND METHODS: This is a cross-sectional questionnaire-based study in the
      public schools located in the urban, rural and slum areas of Chandigarh. Teachers
      were recruited from 20 randomly selected schools out of a total of 103 schools in
      the Union Territory by proportionate sampling. The sample size required for alpha
      of 0.05 and power of 0.80 to detect a difference of 15% from base rate of 35% was
      80. Eighty teachers of 3(rd) and 4(th) grades of these schools were recruited
      using purposive sampling. Teachers were briefed for 5 minutes about the symptoms
      of LD. They were asked questions using a structured questionnaire about their
      socio-demographic status, methods of teaching, and students' progress and their
      perception about LD. Descriptive statistics was mainly used to represent nominal
      and ordinal data using frequency and percentages. Non-parametric statistical
      tests were used to assess relationship between the variables. RESULTS: Eighty
      teachers were recruited, 87.5% were females, 57.5% had more than 5 years teaching
      experience; 56.3% of teachers thought that they were aware of LD, 67.5% of
      teachers perceived that they do encounter children with LD in the school, 43.8%
      endorsed educating such children in special schools, while 36.3% endorsed
      integration to regular schools. Interestingly, more than three fifth of teachers
      were willing to undergo special training for LD intervention. CONCLUSION:
      Teachers acknowledge that there is a need for further steps to be taken to help
      children with LD. They perceive opening special cells or sending such children to
      special schools for appropriate intervention which may not tally with the
      perception of clinician who may wish to provide LD intervention in hospital
      setting.

PMID- 26288788
TI  - Mortality in newborns referred to tertiary hospital: An introspection.
AB  - BACKGROUND: India is one of the largest contributors in the pool of neonatal
      death in the world. However, there are inadequate data on newborns referred to
      tertiary care centers. The present study aimed to find out predictors of
      mortality among newborns delivered elsewhere and admitted in a tertiary hospital
      in New Delhi between February and September 2014. MATERIALS AND METHODS: Hospital
      data for were retrieved and analyzed for determining predictors for mortality of
      the newborns. Time of admission, referral and presenting clinical features were
      considered. RESULTS: Out of 1496 newborns included in the study, there were 300
      deaths. About 43% deaths took place in first 24 hours of life. Asphyxia and low
      birth weight were the main causes of death in early neonatal period, whereas
      sepsis had maximum contribution in deaths during late neonatal period. Severe
      hypothermia, severe respiratory distress, admission within first 24 hours of
      life, absence of health personnel during transport and referral from any hospital
      had significant correlation with mortality. CONCLUSIONS: There is need for ensure
      thermoregulation, respiratory sufficiency and presence of health personnel during
      transport.

PMID- 26288789
TI  - Knowledge about diabetes and relationship between compliance to the management
      among the diabetic patients from Rural Area of Sangli District, Maharashtra,
      India.
AB  - INTRODUCTION: Diabetes is an important public health problem of India. Studies
      have shown that increase in patients' knowledge regarding the disease results in
      better compliance to treatment and decrease in complications. This study was
      planned to assess the knowledge about diabetes and its correlation with
      pharmacological and non-pharmacological compliance, among the diabetic patients
      attending rural health center from Sangli District, Maharashtra (India).
      MATERIALS AND METHODS: The study was conducted during September to November 2014.
      The study subjects were all willing adult patients with type II diabetes mellitus
      attending a selected rural hospital. The study tool was pretested and self
      administered questionnaire. Analysis was done using Microsoft Excel and SPSS-22.
      RESULTS: Total study participants were 307 in number, with the mean age of 55.6
      years. The mean morbidity with diabetes was 10.7 years. Only 23.8% had good
      knowledge regarding diabetes, while 19.2% participants had poor knowledge.
      Knowledge was significantly associated with the compliance to the pharmacological
      and non-pharmacological management. CONCLUSION: Although most of the patients
      were suffering with diabetes for many years there is lack of knowledge regarding
      the disease and self care. The compliance to the management of diabetes was
      better in patients with good knowledge. Seminars, counseling sessions and
      workshop should be arranged periodically for diabetic patients to increase their
      awareness.

PMID- 26288790
TI  - Contaminated tooth brushes-potential threat to oral and general health.
AB  - BACKGROUND: Tooth brushing is most common method of maintaining oral hygiene. In
      removing plaque and other soft debris from the teeth, tooth brushes become
      contaminated with bacteria, blood, saliva and oral debris. These contaminated
      tooth brushes can be a source of infection. AIMS AND OBJECTIVES: The aim of the
      present study was to evaluate the presence of microorganisms in the tooth brushes
      and to investigate the effect of disinfectants such as chlorhexidine gluconate,
      sodium hypochlorite and water to decontaminate them. MATERIALS AND METHODS:
      Twenty-one children were asked to brush their teeth for 5 days with a tooth
      brush. The tooth brushes were put in Robertson's Cooked Meat broth and were
      observed for growth of Streptococcal microorganisms. These tooth brushes were
      then placed in disinfectants such as 0.2% chlorhexidine gluconate (Group I), 1%
      sodium hypochlorite (Group II) and water (Group III) for 24 hrs and then cultured
      again. Reduction of growth of microorganisms was seen in Group I, Group II and
      remnants of growth seen in Group III. CONCLUSION: We conclude that the use of
      disinfectant for a tooth brush is a must for every individual at least at regular
      intervals.

PMID- 26288791
TI  - Perception of stigma toward mental illness in South India.
AB  - BACKGROUND: Stigma associated with mental illnesses is one of the principal
      causes for mentally ill people not receiving adequate mental health care and
      treatment. The study was conducted to assess the extent of stigma associated with
      mental illness and knowledge of mental illness among the community. MATERIALS AND
      METHODS: Community-based, cross-sectional study was conducted among 445
      respondents from Udupi district; the community attitude toward the mentally ill
      (CAMI) scale was used to assess stigma. The probability proportional to sampling
      size technique was adopted to select the wards/blocks. Household from
      blocks/wards were selected using convenience sampling. Self- administered semi
      structured questionnaire was used to collect the information. Data was analyzed
      using the software SPSS version 15. RESULTS: Of the total 445 respondents, the
      prevalence of stigma toward mentally ill people was 74.61% (95% confidence
      interval, 0.7057, 0.7866). The prevalence of stigma was high under all the four
      domains of CAMI scale. High prevalence of stigma was seen among females and
      people with higher income. CONCLUSIONS: The overall prevalence of stigma toward
      PWMI was found to be high. The stigma toward PWMI was associated with gender with
      respect to AU, BE and CMHI. Hence, the study suggests that there is a strong need
      to eliminate stigma associated with mental illness to improve the mental health
      status of the region.

PMID- 26288792
TI  - The prediction of postpartum depression: The role of the PRECEDE model and health
      locus of control.
AB  - BACKGROUND: The main purpose of this study was to investigate the effect of the
      PRECEDE model and health locus of control (HLC) on postpartum depression. This
      study used the path analysis to test the pattern of causal relations through the
      correlation coefficients. MATERIALS AND METHOD: The participants included 230
      pregnant women in the north-east of Iran who were selected by convenience
      sampling. To analyze data, Pearson correlation and path analysis were applied to
      examine the relationships between variables using SPSS 20 and LISREL
      8.50software. RESULTS: The result of path analysis showed that a positive
      correlation exists between predisposing (knowledge, internal HLC, powerful others
      HLC, chance HLC) enabling and reinforcing factors with postpartum depression by
      GHQ score (GFI = 1, RSMEA = 000). CONCLUSION: The current study supported the
      application of the PRECEDE model and HLC in understanding the promoting behaviors
      in mental health and demonstrated their relationships with postpartum depression.

PMID- 26288793
TI  - Dietary calcium intake and physical activity levels among urban South Indian
      postmenopausal women.
AB  - INTRODUCTION: Calcium is the most abundant mineral in our body with varied
      functions and its dietary deficiency leads to osteoporosis, besides playing a
      significant role in the pathogenesis of other diseases. The data regarding
      dietary calcium intake (DCI) among postmenopausal women in urban areas of South
      India is limited. OBJECTIVES: This study was aimed to assess DCI and physical
      activity among postmenopausal women. The risk factors for a low intake of dietary
      calcium were also assessed. MATERIALS AND METHODS: A cross-sectional study was
      done among 106 postmenopausal women selected by systematic random sampling from
      the city of Erode, Tamil Nadu, India. DCI and physical activity were measured
      using validated questionnaires. RESULTS: The mean DCI was 632.72 +/- 28.23
      mg/day. The proportion of women consuming less than 800 mg/day of dietary calcium
      was 74.5%. Only 10.4% of the women studied (11 out of 106) were on calcium
      supplements while 55% had low physical activity. A low knowledge score [adjusted
      odds ratio (OR): 5.17; 95% confidence interval (CI): 1.31-20.42] and a low
      socioeconomic status (SES) score of the family (adjusted OR: 4.00; 95% CI: 1.32
      12.11) were significantly associated with low DCI after adjusting the age,
      dietary preferences, and educational and occupational statuses. CONCLUSIONS: DCI
      was below the Recommended Dietary Allowance (RDA) and the majority of
      postmenopausal women were physically inactive, indicating the need for better
      education regarding DCI and the need for calcium supplements and physical
      activity, all of which can contribute to the prevention of the consequences of
      osteoporosis.

PMID- 26288795
TI  - The leadership crisis of medical profession in India: Ongoing impact on the
      health system.

PMID- 26288794
TI  - An uncommon cause for hip pain and limping.
AB  - Slipped capital femoral epiphysis (SCFE) is characterized by displacement of the
      capital femoral epiphysis from the femoral neck. An 18-year-old male presented
      with left hip pain and a limping gait, following a trivial trauma. Radiological
      examination revealed bilateral SCFE. Clinically and biochemically, he had
      features of hypopituitarism. His prolactin levels were high and magnetic
      resonance imaging (MRI) scan showed a pituitary macroadenoma, suggesting a
      diagnosis of macroprolactinoma causing hypopituitarism and presenting as SCFE. He
      was started on dopamine agonist cabergoline as well as thyroxine and
      glucocorticoid replacement treatment. He was also scheduled for an orthopedic
      surgical procedure for his SCFE. 

PMID- 26288796
TI  - What individual doctors can do to counter the leadership crises in medical
      profession?

PMID- 26288797
TI  - Clinical audit and lifelong reflective practice as game changers to integrate
      medical education and practice.

PMID- 26288798
TI  - Pneumoperitoneum: What to look for in a radiograph?

PMID- 26288799
TI  - E74-like factor inhibition induces reacquisition of hormone sensitiveness
      decreasing period circadian protein homolog 1 expression in prostate cancer
      cells.
AB  - PURPOSE: Initiating as an androgen-dependent adenocarcinoma, prostate cancer
      (PCa) gradually progresses to a castrate-resistant disease following androgen
      deprivation therapy with a propensity to metastasize. METHODS: In order to
      resolve the mechanism of castrate-resistant PCa, we performed a cDNA-microarray
      assay of two PCa cell lines, LNCaP (androgen dependent) and C4-2 (androgen
      independent). Among them, we focused on a novel Ets transcription factor, E74
      like factor 5 (ELF5), the expression level of which was extremely high in C4-2 in
      comparison with LNCaP both in the microarray analysis and real-time polymerase
      chain reaction analysis, and investigated the biological role in acquisition of
      androgen-refractory PCa growth. RESULTS: Western blot analysis and morphological
      analysis using confocal immunofluorescence microscopy demonstrated that ELF5 was
      expressed mainly in cytosol both in LNCaP and C4-2. Inhibition of ELF5 expression
      using ELF5-small interfering RNA in C4-2 induced decreased expression of androgen
      receptor corepressor, period circadian protein homolog 1, and MTT assay of C4-2
      after ELF5 small interfering RNA transfection showed the same cell growth pattern
      of LNCaP. CONCLUSIONS: Our in vitro experiments of cell growth and microarray
      analysis have demonstrated for the first time that decreased expression of period
      circadian protein homolog 1 due to ELF5 inhibition may induce the possibility of
      reacquisition of hormone sensitiveness of PCa cells. We suggest that ELF5 could
      be a novel potential target for the treatment of hormone-refractory PCa patients.

PMID- 26288801
TI  - Van Gogh's Physician.

PMID- 26288800
TI  - Congenital Parvovirus B19 Infection: Persistent Viremia and Red Blood Cell
      Aplasia.
AB  - We describe a case of fetal parvovirus B19 infection resulting in preterm birth
      and leading to hydrops fetalis requiring multiple in utero transfusions. The
      infant developed chronic postnatal anemia responsive to intravenous
      immunoglobulin therapy. Serum viral load decreased after immunoglobulin treatment
      but remained detectable for over 1 year. 

PMID- 26288802
TI  - Data in support of environmental controls on the characteristics of mean number
      of forest fires and mean forest area burned (1987-2007) in China.
AB  - Fire frequency and size are two important parameters describing fire
      characteristics. Exploring the spatial variation of fire characteristics and
      understanding the environmental controls are indispensable to fire prediction and
      sustainable forest landscape management. To illustrate the spatial variation of
      forest fire characteristics over China and to quantitatively determine the
      relative contribution of each of the environmental controls to this variation,
      forest fire characteristic data (mean number of forest fires and mean burned
      forest area) and environmental data (climate, land use, vegetation type and
      topography) at provincial level were derived. These data sets can potentially
      serve as a foundation for future studies relating to fire risk assessment, carbon
      emission by forest fires, and the impact of climate change on fire
      characteristics. This data article contains data related to the research article
      entitled "Environmental controls on the characteristics of mean number of forest
      fires and mean forest area burned (1987-2007) in China" by chang et al. [1]. 

PMID- 26288803
TI  - Three-dimensional visualization of multiple synapses in thick sections using high
      voltage electron microscopy in the rat spinal cord.
AB  - This data article contains complementary figure and movies (Supplementary Movies
      1-3) related to the research article entitled, "Effective synaptome analysis of
      itch-mediating neurons in the spinal cord: a novel immunohistochemical
      methodology using high-voltage electron microscopy" [7]. It is important to show
      the synaptic connections at the ultrastructural level to understand the neural
      circuit, which requires the three-dimensional (3-D) analyses in the electron
      microscopy. Here, we applied a new sample preparation method, a high-contrast en
      bloc staining according to the protocol of the National Center for Microscopy and
      Imaging Research (NCMIR), University of California, San Diego, CA, USA to high
      voltage electron microscopy (HVEM) tomography in order to examine the 3-D
      chemical neuroanatomy of the rat spinal cord. Pre-embedding immunoelectron
      microscopy was used in this study. HVEM has an excellent potential to directly
      visualize the ultrastructures in semi-thin sections (~5 MUm thick), and we have
      successfully visualized many itch-mediating synaptic connections and neural
      networks in the spinal cord using "HVEM tomography". Moreover, the methodology
      used in this study is simple and can be applied in multiple ways. This is an
      important contribution to ultrastructural investigations of the central nervous
      system in the present post-genomic age. 

PMID- 26288804
TI  - Hospital-acquired Infections - A Clean Bill of Health?

PMID- 26288805
TI  - Is Cancer a Genetic Disease or a Metabolic Disease?

PMID- 26288806
TI  - WNT Takes Centre Stage in Border Control.

PMID- 26288807
TI  - Cooling-Induced ER Stress is Good for Your Brain.

PMID- 26288808
TI  - Electron Transfer-Based Compounds: A Novel Weapon in the Cancer Battlespace?

PMID- 26288809
TI  - Nanoparticle Formulation to Improve the Efficacy of Radiation Therapy Against
      Radiation-resistant Leukemia.

PMID- 26288810
TI  - Epigenetic Gene Mutations Impact on Outcome in Acute Myeloid Leukaemia.

PMID- 26288811
TI  - Written in Blood: Kissing Disease miRNAs Could Predict Outcome of Patients With
      Chronic Lymphocytic Leukaemia.

PMID- 26288813
TI  - Novel Method for Screening Colorectal Neoplasm.

PMID- 26288812
TI  - Lung Cancer Risk, Genetic Variation, and Air Pollution.

PMID- 26288814
TI  - Development of Serum DHCR24 Antibody as a Marker for Hepatocellular Carcinoma:
      The End of the Beginning.

PMID- 26288815
TI  - Altered Mitochondrial Function, Mitochondrial DNA and Reduced Metabolic
      Flexibility in Patients With Diabetic Nephropathy.
AB  - The purpose of this study was to determine if mitochondrial dysfunction plays a
      role in diabetic nephropathy (DN), a kidney disease which affects > 100 million
      people worldwide and is a leading cause of renal failure despite therapy. A cross
      sectional study comparing DN with diabetes patients without kidney disease (DC)
      and healthy controls (HCs); and renal mesangial cells (HMCs) grown in normal and
      high glucose, was carried out. Patients with diabetes (DC) had increased
      circulating mitochondrial DNA (MtDNA), and HMCs increased their MtDNA within 24 h
      of hyperglycaemia. The increased MtDNA content in DCs and HMCs was not functional
      as transcription was unaltered/down-regulated, and MtDNA damage was present.
      MtDNA was increased in DC compared to HC, conversely, patients with DN had lower
      MtDNA than DC. Hyperglycaemic HMCs had fragmented mitochondria and TLR9 pathway
      activation, and in diabetic patients, mitophagy was reduced. Despite MtDNA
      content and integrity changing within 4 days, hyperglycaemic HMCs had a normal
      bio-energetic profile until 8 days, after which mitochondrial metabolism was
      progressively impaired. Peripheral blood mononuclear cells (PBMCs) from DN
      patients had reduced reserve capacity and maximal respiration, loss of metabolic
      flexibility and reduced Bioenergetic Health Index (BHI) compared to DC. Our data
      show that MtDNA changes precede bioenergetic dysfunction and that patients with
      DN have impaired mitochondrial metabolism compared to DC, leading us to propose
      that systemic mitochondrial dysfunction initiated by glucose induced MtDNA damage
      may be involved in the development of DN. Longitudinal studies are needed to
      define a potential cause-effect relationship between changes in MtDNA and
      bioenergetics in DN. 

PMID- 26288816
TI  - Fate Specification of Neural Plate Border by Canonical Wnt Signaling and Grhl3 is
      Crucial for Neural Tube Closure.
AB  - During primary neurulation, the separation of a single-layered ectodermal sheet
      into the surface ectoderm (SE) and neural tube specifies SE and neural ectoderm
      (NE) cell fates. The mechanisms underlying fate specification in conjunction with
      neural tube closure are poorly understood. Here, by comparing expression profiles
      between SE and NE lineages, we observed that uncommitted progenitor cells,
      expressing stem cell markers, are present in the neural plate border/neural fold
      prior to neural tube closure. Our results also demonstrated that canonical Wnt
      and its antagonists, DKK1/KREMEN1, progressively specify these progenitors into
      SE or NE fates in accord with the progress of neural tube closure. Additionally,
      SE specification of the neural plate border via canonical Wnt signaling is
      directed by the grainyhead-like 3 (Grhl3) transcription factor. Thus, we propose
      that the fate specification of uncommitted progenitors in the neural plate border
      by canonical Wnt signaling and its downstream effector Grhl3 is crucial for
      neural tube closure. This study implicates that failure in critical genetic
      factors controlling fate specification of progenitor cells in the neural plate
      border/neural fold coordinated with neural tube closure may be potential causes
      of human neural tube defects. 

PMID- 26288817
TI  - GLI3 Links Environmental Arsenic Exposure and Human Fetal Growth.
AB  - Although considerable evidence suggests that in utero arsenic exposure affects
      children's health, these data are mainly from areas of the world where
      groundwater arsenic levels far exceed the World Health Organization limit of 10
      MUg/L. We, and others, have found that more common levels of in utero arsenic
      exposure may also impact children's health. However, the underlying molecular
      mechanisms are poorly understood. To address this issue, we analyzed the
      expression of key developmental genes in fetal placenta in a birth cohort of
      women using unregulated water supplies in a US region with elevated groundwater
      arsenic. We identified several genes whose expression associated with maternal
      arsenic exposure in a fetal sex-specific manner. In particular, expression of the
      HEDGEHOG pathway component, GLI3, in female placentae was both negatively
      associated with arsenic exposure and positively associated with infant birth
      weight. This suggests that modulation of GLI3 in the fetal placenta, and perhaps
      in other fetal tissues, contributes to arsenic's detrimental effects on fetal
      growth. We showed previously that arsenic-exposed NIH3T3 cells have reduced GLI3
      repressor protein. Together, these studies identify GLI3 as a key signaling node
      that is affected by arsenic, mediating a subset of its effects on developmental
      signaling and fetal health. 

PMID- 26288818
TI  - Epstein-Barr Virus MicroRNAs are Expressed in Patients with Chronic Lymphocytic
      Leukemia and Correlate with Overall Survival.
AB  - Although numerous studies highlighted the role of Epstein-Barr Virus (EBV) in B
      cell transformation, the involvement of EBV proteins or genome in the development
      of the most frequent adult leukemia, chronic lymphocytic leukemia (CLL), has not
      yet been defined. We hypothesized that EBV microRNAs contribute to progression of
      CLL and demonstrated the presence of EBV miRNAs in B-cells, in paraffin-embedded
      bone marrow biopsies and in the plasma of patients with CLL by using three
      different methods (small RNA-sequencing, quantitative reverse transcription PCR
      [q-RT-PCR] and miRNAs in situ hybridization [miRNA-ISH]). We found that EBV miRNA
      BHRF1-1 expression levels were significantly higher in the plasma of patients
      with CLL compared with healthy individuals (p < 0 . 0001). Notably, BHRF1-1 as
      well as BART4 expression were detected in the plasma of either seronegative or
      seropositive (anti-EBNA-1 IgG and EBV DNA tested) patients; similarly, miRNA-ISH
      stained positive in bone marrow specimens while LMP1 and EBER
      immunohistochemistry failed to detect viral proteins and RNA. We also found that
      BHRF1-1 plasma expression levels were positively associated with elevated beta-2
      microglobulin levels and advanced Rai stages and observed a correlation between
      higher BHRF1-1 expression levels and shorter survival in two independent
      patients' cohorts. Furthermore, in the majority of CLL cases where BHRF1-1 was
      exogenously induced in primary malignant B cells the levels of TP53 were reduced.
      Our findings suggest that EBV may have a role in the process of disease
      progression in CLL and that miRNA RT-PCR and miRNAs ISH could represent
      additional methods to detect EBV miRNAs in patients with CLL. 

PMID- 26288819
TI  - Characterization of Somatic Mutations in Air Pollution-Related Lung Cancer.
AB  - Air pollution has been classified as Group 1 carcinogenic to humans, but the
      underlying tumorigenesis remains unclear. In Xuanwei City of Yunnan Province, the
      lung cancer incidence is among the highest in China attributed to severe air
      pollution generated by combustion of smoky coal, providing a unique opportunity
      to dissect lung carcinogenesis of air pollution. Here we analyzed the somatic
      mutations of 164 non-small cell lung cancers (NSCLCs) from Xuanwei and control
      regions (CR) where smoky coal was not used. Whole genome sequencing revealed a
      mean of 289 somatic exonic mutations per tumor and the frequent C:G -> A:T
      nucleotide substitutions in Xuanwei NSCLCs. Exome sequencing of 2010 genes showed
      that Xuanwei and CR NSCLCs had a mean of 68 and 22 mutated genes per tumor,
      respectively (p < 0.0001). We found 167 genes (including TP53, RYR2, KRAS,
      CACNA1E) which had significantly higher mutation frequencies in Xuanwei than CR
      patients, and mutations in most genes in Xuanwei NSCLCs differed from those in CR
      cases. The mutation rates of 70 genes (e.g., RYR2, MYH3, GPR144, CACNA1E) were
      associated with patients' lifetime benzo(a)pyrene exposure. This study uncovers
      the mutation spectrum of air pollution-related lung cancers, and provides
      evidence for pollution exposure-genomic mutation relationship at a large scale. 

PMID- 26288820
TI  - Blood Telomere Length Attrition and Cancer Development in the Normative Aging
      Study Cohort.
AB  - BACKGROUND: Accelerated telomere shortening may cause cancer via chromosomal
      instability, making it a potentially useful biomarker. However, publications on
      blood telomere length (BTL) and cancer are inconsistent. We prospectively
      examined BTL measures over time and cancer incidence. METHODS: We included 792
      Normative Aging Study participants with 1-4 BTL measurements from 1999 to 2012.
      We used linear mixed-effects models to examine BTL attrition by cancer status
      (relative to increasing age and decreasing years pre-diagnosis), Cox models for
      time-dependent associations, and logistic regression for cancer incidence
      stratified by years between BTL measurement and diagnosis. FINDINGS: Age-related
      BTL attrition was faster in cancer cases pre-diagnosis than in cancer-free
      participants (pdifference = 0.017); all participants had similar age-adjusted BTL
      8-14 years pre-diagnosis, followed by decelerated attrition in cancer cases
      resulting in longer BTL three (p = 0.003) and four (p = 0.012) years pre
      diagnosis. Longer time-dependent BTL was associated with prostate cancer (HR =
      1.79, p = 0.03), and longer BTL measured <= 4 years pre-diagnosis with any (OR =
      3.27, p < 0.001) and prostate cancers (OR = 6.87, p < 0.001). INTERPRETATION: Age
      related BTL attrition was faster in cancer cases but their age-adjusted BTL
      attrition began decelerating as diagnosis approached. This may explain prior
      inconsistencies and help develop BTL as a cancer detection biomarker.

PMID- 26288821
TI  - Fecal Microbiota Characteristics of Patients with Colorectal Adenoma Detected by
      Screening: A Population-based Study.
AB  - BACKGROUND: Screening for colorectal cancer (CRC) and precancerous colorectal
      adenoma (CRA) can detect curable disease. However, participation in colonoscopy
      and sensitivity of fecal heme for CRA are low. METHODS: Microbiota metrics were
      determined by Illumina sequencing of 16S rRNA genes amplified from DNA extracted
      from feces self-collected in RNAlater. Among fecal immunochemical test-positive
      (FIT +) participants, colonoscopically-defined normal versus CRA patients were
      compared by regression, permutation, and random forest plus leave-one-out
      methods. FINDINGS: Of 95 FIT + participants, 61 had successful fecal microbiota
      profiling and colonoscopy, identifying 24 completely normal patients, 20 CRA
      patients, 2 CRC patients, and 15 with other conditions. Phylum-level fecal
      community composition differed significantly between CRA and normal patients
      (permutation P = 0.02). Rank phylum-level abundance distinguished CRA from normal
      patients (area under the curve = 0.767, permutation P = 0.006). CRA prevalence
      was 59% in phylum-level cluster B versus 20% in cluster A (exact P = 0.01). Most
      of the difference reflected 3-fold higher median relative abundance of
      Proteobacteria taxa (Wilcoxon signed-rank P = 0.03, positive predictive value =
      67%). Antibiotic exposure and other potential confounders did not affect the
      associations. INTERPRETATION: If confirmed in larger, more diverse populations,
      fecal microbiota analysis might be employed to improve screening for CRA and
      ultimately to reduce mortality from CRC.

PMID- 26288823
TI  - Banning Psychoactive Substances: A Slippery Slope.

PMID- 26288822
TI  - Serum DHCR24 Auto-antibody as a new Biomarker for Progression of Hepatitis C.
AB  - BACKGROUND: New biomarkers are needed to identify the stage of hepatitis C virus
      (HCV)-infected diseases in order to reduce the mortality rates. Herein, we
      investigated whether serum 3beta-hydroxysterol Delta24-reductase antibody (DHCR24
      Ab) may serve as a prognostic marker for hepatitis C infection progression to
      hepatocellular carcinoma (HCC). METHODS: Serum DHCR24 Abs from 395 HCV-positive
      patients, including 133 chronic hepatitis (CHC), 85 liver cirrhosis (LCC), and
      177 HCC (HCC-C) patients; 232 hepatitis B virus (HBV)-positive patients,
      including 103 chronic hepatitis (CHB), 56 liver cirrhosis (LCB), and 73 HCC (HCC
      B) patients; and 24 healthy controls, were measured using enzyme-linked
      immunosorbent assay. RESULTS: The serum DHCR24 Ab levels were significantly
      higher in patients with CHC than in healthy controls, in LCC than in CHC, and in
      LCC than in HCC-C (P < 0.0001 for all). The concentration of serum DHCR24 Ab in
      HCC-B patients showed no significant difference compared to CHB and LCB patients
      (P = 0.1247). The DHCR24 Ab levels were significantly higher in early HCC-C than
      CHC or LCC patients and in late HCC-C compared to early HCC-C patients. The
      sensitivity of the DHCR24 Ab for HCC-C detection (70.6%) was higher than that of
      alpha-fetoprotein (AFP; 54.8%) and protein induced by vitamin K absence or
      antagonist-II (PIVKA-II; 42 . 5%). Moreover, DHCR24 was up-regulated in HCV
      positive, but not HBV-positive tissues or HBV-negative, HCV-negative HCC
      specimens. CONCLUSIONS: DHCR24 auto-antibody represents a potential noninvasive
      biomarker for HCV-related liver disease and may facilitate the diagnosis of PIVKA
      II and AFP-negative HCC.

PMID- 26288824
TI  - Antibiotic Development and the Evolving Role of Pharmacodynamics - As Good as It
      Gets?

PMID- 26288825
TI  - European Society of Human Genetics (ESHG) Conference, June 6-9, 2015, Glasgow,
      UK.

PMID- 26288826
TI  - Proteasome inhibition by bortezomib: A left hook and a right punch.

PMID- 26288827
TI  - Can we be SMaRT-er in our approach to cancer therapy?

PMID- 26288828
TI  - Retinoblastoma Progression.

PMID- 26288829
TI  - Evaluating New Ways of Working Collectively in Science with a Focus on
      Crowdsourcing.

PMID- 26288830
TI  - Rethinking the Antibiotic Discovery Paradigm.

PMID- 26288831
TI  - Cytomegalovirus: Why Viral Dynamics Matter.

PMID- 26288832
TI  - Origins of a Vaccine-Induced, Human Anti-HIV-1 Antibody.

PMID- 26288833
TI  - Inflammation: Friend and Foe.

PMID- 26288834
TI  - Enteroviruses and Type 1 Diabetes: Candidate Genes Linked With Innate Immune
      Response.

PMID- 26288835
TI  - Ocular Pseudoexfoliation Syndrome and Life Span: Act 2.

PMID- 26288836
TI  - Bortezomib Amplifies Effect on Intracellular Proteasomes by Changing Proteasome
      Structure.
AB  - The proteasome inhibitor Bortezomib is used to treat multiple myeloma (MM).
      Bortezomib inhibits protein degradation by inactivating proteasomes' active
      sites. MM cells are exquisitely sensitive to Bortezomib - exhibiting a low
      nanomolar IC(50) - suggesting that minimal inhibition of degradation suffices to
      kill MM cells. Instead, we report, a low Bortezomib concentration, contrary to
      expectation, achieves severe inhibition of proteasome activity in MM cells: the
      degree of inhibition exceeds what one would expect from the small proportion of
      active-sites that Bortezomib inhibits. Our data indicate that Bortezomib achieves
      this severe inhibition by triggering secondary changes in proteasome structure
      that further inhibit proteasome activity. Comparing MM cells to other, Bortezomib
      resistant, cancer cells shows that the degree of proteasome inhibition is the
      greatest in MM cells and only there leads to proteasome stress, providing an
      explanation for why Bortezomib is effective against MM but not other cancers. 

PMID- 26288837
TI  - Development of Polypeptide-based Nanoparticles for Non-viral Delivery of CD22 RNA
      Trans-splicing Molecule as a New Precision Medicine Candidate Against B-lineage
      ALL.
AB  - CD22DeltaE12 has emerged as a driver lesion in the pathogenesis of pediatric B
      lineage acute lymphoblastic leukemia (ALL) and a new molecular target for RNA
      therapeutics. Here we report a 43-gene CD22DeltaE12 signature transcriptome that
      shows a striking representation in primary human leukemia cells from patients
      with relapsed BPL. Our data uniquely indicate that CD22DeltaE12 is a candidate
      driver lesion responsible for the activation of MAPK and PI3-K pathways in
      aggressive forms of B-lineage ALL. We also show that the forced expression of a
      CD22 RNA trans-splicing molecule (RTM) markedly reduces the capacity of the
      leukemic stem cell fraction of CD22DeltaE12(+) B-lineage ALL cells to engraft and
      cause overt leukemia in NOD/SCID mice. We have successfully complexed our
      rationally designed lead CD22-RTM with PVBLG-8 to prepare a non-viral nanoscale
      formulation of CD22DeltaE12-RTM with potent anti-cancer activity against
      CD22DeltaE12(+) B-lineage leukemia and lymphoma cells. CD22-RTM nanoparticles
      effectively delivered the CD22-RTM cargo into B-lineage ALL cells and exhibited
      significant anti-leukemic activity in vitro. 

PMID- 26288838
TI  - Loss of photoreceptorness and gain of genomic alterations in retinoblastoma
      reveal tumor progression.
AB  - BACKGROUND: Retinoblastoma is a pediatric eye cancer associated with RB1 loss or
      MYCN amplification (RB1 (+/+) MYCN(A) ). There are controversies concerning the
      existence of molecular subtypes within RB1(-/-) retinoblastoma. To test whether
      these molecular subtypes exist, we performed molecular profiling. METHODS: Genome
      wide mRNA expression profiling was performed on 76 primary human retinoblastomas.
      Expression profiling was complemented by genome-wide DNA profiling and clinical,
      histopathological, and ex vivo drug sensitivity data. FINDINGS: RNA and DNA
      profiling identified major variability between retinoblastomas. While gene
      expression differences between RB1 (+/+) MYCN(A) and RB1(-/-) tumors seemed more
      dichotomous, differences within the RB1(-/-) tumors were gradual. Tumors with
      high expression of a photoreceptor gene signature were highly differentiated,
      smaller in volume and diagnosed at younger age compared with tumors with low
      photoreceptor signature expression. Tumors with lower photoreceptor expression
      showed increased expression of genes involved in M-phase and mRNA and ribosome
      synthesis and increased frequencies of somatic copy number alterations.
      INTERPRETATION: Molecular, clinical and histopathological differences between
      RB1(-/-) tumors are best explained by tumor progression, reflected by a gradual
      loss of differentiation and photoreceptor expression signature. Since copy number
      alterations were more frequent in tumors with less photoreceptorness, genomic
      alterations might be drivers of tumor progression. RESEARCH IN CONTEXT:
      Retinoblastoma is an ocular childhood cancer commonly caused by mutations in the
      RB1 gene. In order to determine optimal treatment, tumor subtyping is considered
      critically important. However, except for very rare retinoblastomas without an
      RB1 mutation, there are controversies as to whether subtypes of retinoblastoma do
      exist. Our study shows that retinoblastomas are highly diverse but rather than
      reflecting distinct tumor types with a different etiology, our data suggests that
      this diversity is a result of tumor progression driven by cumulative genetic
      alterations. Therefore, retinoblastomas should not be categorized in distinct
      subtypes, but be described according to their stage of progression.

PMID- 26288839
TI  - The Prognostic and Predictive Value of Melanoma-related MicroRNAs Using Tissue
      and Serum: A MicroRNA Expression Analysis.
AB  - The overall 5-year survival for melanoma is 91%. However, if distant metastasis
      occurs (stage IV), cure rates are < 15%. Hence, melanoma detection in earlier
      stages (stages I-III) maximises the chances of patient survival. We measured the
      expression of a panel of 17 microRNAs (miRNAs) (MELmiR-17) in melanoma tissues
      (stage III; n = 76 and IV; n = 10) and serum samples (collected from controls
      with no melanoma, n = 130; and patients with melanoma (stages I/II, n = 86; III,
      n = 50; and IV, n = 119)) obtained from biobanks in Australia and Germany. In
      melanoma tissues, members of the 'MELmiR-17' panel were found to be predictors of
      stage, recurrence, and survival. Additionally, in a minimally-invasive blood
      test, a seven-miRNA panel (MELmiR-7) detected the presence of melanoma (relative
      to controls) with high sensitivity (93%) and specificity (>= 82%) when >= 4
      miRNAs were expressed. Moreover, the 'MELmiR-7' panel characterised overall
      survival of melanoma patients better than both serum LDH and S100B (delta log
      likelihood = 11, p < 0.001). This panel was found to be superior to currently
      used serological markers for melanoma progression, recurrence, and survival; and
      would be ideally suited to monitor tumour progression in patients diagnosed with
      early metastatic disease (stages IIIa-c/IV M1a-b) to detect relapse following
      surgical or adjuvant treatment. 

PMID- 26288840
TI  - Crowdsourcing the General Public for Large Scale Molecular Pathology Studies in
      Cancer.
AB  - BACKGROUND: Citizen science, scientific research conducted by non-specialists,
      has the potential to facilitate biomedical research using available large-scale
      data, however validating the results is challenging. The Cell Slider is a citizen
      science project that intends to share images from tumors with the general public,
      enabling them to score tumor markers independently through an internet-based
      interface. METHODS: From October 2012 to June 2014, 98,293 Citizen Scientists
      accessed the Cell Slider web page and scored 180,172 sub-images derived from
      images of 12,326 tissue microarray cores labeled for estrogen receptor (ER). We
      evaluated the accuracy of Citizen Scientist's ER classification, and the
      association between ER status and prognosis by comparing their test performance
      against trained pathologists. FINDINGS: The area under ROC curve was 0.95 (95% CI
      0.94 to 0.96) for cancer cell identification and 0.97 (95% CI 0.96 to 0.97) for
      ER status. ER positive tumors scored by Citizen Scientists were associated with
      survival in a similar way to that scored by trained pathologists. Survival
      probability at 15 years were 0.78 (95% CI 0.76 to 0.80) for ER-positive and 0.72
      (95% CI 0.68 to 0.77) for ER-negative tumors based on Citizen Scientists
      classification. Based on pathologist classification, survival probability was
      0.79 (95% CI 0.77 to 0.81) for ER-positive and 0.71 (95% CI 0.67 to 0.74) for ER
      negative tumors. The hazard ratio for death was 0.26 (95% CI 0.18 to 0.37) at
      diagnosis and became greater than one after 6.5 years of follow-up for ER scored
      by Citizen Scientists, and 0.24 (95% CI 0.18 to 0.33) at diagnosis increasing
      thereafter to one after 6.7 (95% CI 4.1 to 10.9) years of follow-up for ER scored
      by pathologists. INTERPRETATION: Crowdsourcing of the general public to classify
      cancer pathology data for research is viable, engages the public and provides
      accurate ER data. Crowdsourced classification of research data may offer a valid
      solution to problems of throughput requiring human input.

PMID- 26288841
TI  - Azithromycin Synergizes with Cationic Antimicrobial Peptides to Exert
      Bactericidal and Therapeutic Activity Against Highly Multidrug-Resistant Gram
      Negative Bacterial Pathogens.
AB  - Antibiotic resistance poses an increasingly grave threat to the public health. Of
      pressing concern, rapid spread of carbapenem-resistance among multidrug-resistant
      (MDR) Gram-negative rods (GNR) is associated with few treatment options and high
      mortality rates. Current antibiotic susceptibility testing guiding patient
      management is performed in a standardized manner, identifying minimum inhibitory
      concentrations (MIC) in bacteriologic media, but ignoring host immune factors.
      Lacking activity in standard MIC testing, azithromycin (AZM), the most commonly
      prescribed antibiotic in the U.S., is never recommended for MDR GNR infection.
      Here we report a potent bactericidal action of AZM against MDR carbapenem
      resistant isolates of Pseudomonas aeruginosa, Klebsiella pneumoniae, and
      Acinetobacter baumannii. This pharmaceutical activity is associated with enhanced
      AZM cell penetration in eukaryotic tissue culture media and striking multi-log
      fold synergies with host cathelicidin antimicrobial peptide LL-37 or the last
      line antibiotic colistin. Finally, AZM monotherapy exerts clear therapeutic
      effects in murine models of MDR GNR infection. Our results suggest that AZM,
      currently ignored as a treatment option, could benefit patients with MDR GNR
      infections, especially in combination with colistin. 

PMID- 26288842
TI  - Clinical Application of Variation in Replication Kinetics During Episodes of Post
      transplant Cytomegalovirus Infections.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection in transplant recipients is reported
      to replicate with a doubling time of 1.2-2 days, and weekly screening is
      recommended for early diagnosis. We re-evaluated these features in our cohort of
      transplant recipients. METHODS: The CMV doubling time of the first CMV infection
      in the first year post-transplant could be calculated for 193 recipients of
      haematopoietic stem cell or solid organ transplantation. Factors determining the
      proportion of recipients with a high diagnostic CMV viral load (>= 18,200 IU/mL)
      were explored using mathematical simulation. FINDINGS: The overall median
      doubling time was 4.3 days (IQR 2.5-7.8) and was not influenced by prior CMV
      immunity, or type of transplantation (p > 0.4). Assuming a fixed doubling time of
      1.3 days and screening intervals of 7 or 10 days, 11.1% and 33.3% were projected
      to have a high CMV viral load at diagnosis, compared to 1.4% and 4.3% if the
      doubling time varies as observed in our cohort. Consistently, 1.9% of recipients
      screened weekly had a high diagnostic virus load. INTERPRETATION: Screening
      intervals can be extended to 10 days in cohorts with comparable CMV doubling
      time, whereas shorter than 7 days is required in cohorts with shorter doubling
      times to maintain pre-emptive screening quality.

PMID- 26288843
TI  - Investigation of Efavirenz Discontinuation in Multi-ethnic Populations of HIV
      positive Individuals by Genetic Analysis.
AB  - BACKGROUND: Efavirenz (EFV) based antiretroviral therapy is expanding worldwide.
      However discontinuation of EFV containing regimens is common in some patients,
      particularly black patients, due most often to neuropsychiatric side effects.
      These adverse drug effects often result in premature drug discontinuation, as
      well as considerable morbidity. METHODS: We genotyped CYP2A6, CYP2B6 and CYP3A4,
      which encode enzymes principally involved in EFV metabolism, from patients
      enrolled in the multinational SMART, FIRST and ESPRIT studies, for whom outcome
      data of treatment adherence was available. Patients with loss or decrease of
      function single nucleotide polymorphisms (SNPs) in the above genes were assigned
      a risk score based upon the number of SNPs present weighted relative to whether
      CYP2B6 (main metabolism pathway) and/or CYP2A6 and CYP3A4 (accessory pathways)
      were involved. Cox regression models were used to study the association between
      high genetic risk and time from initiation to EFV discontinuation. Failure was
      defined as discontinuation of an antiretroviral regimen other than for virologic
      failure or protocol determined discontinuation. FINDINGS: Patients with highest
      pharmacogenetic risk, as defined by cumulative SNPs in CYP2A6, CYP2B6 and CYP3A4,
      have an increased risk of discontinuation of EFV containing therapy compared to
      patients with lower genetic risk scores (adjusted HR 1.9, 95% CI 1.2, 3.1, P =
      0.009). High genetic risk score was not associated with an increased risk of
      discontinuing atazanavir or nevirapine. High genetic risk was present more often
      in blacks compared to non-blacks (Adjusted OR 4.5, 95% CI: 1.9,10.5), and
      treatment discontinuation was also increased in blacks overall (Adjusted HR 1.4,
      95% CI 1.0, 1.9). However, high genetic risk was more associated with treatment
      discontinuation than race alone for both blacks (Adjusted OR 1.9, 95% CI 0.8,
      4.8) and non-blacks (Adjusted OR 5.3, 95% CI 1.5, 18.0). INTERPRETATION:
      Premature discontinuation of ART delays the time to effective long term viral
      suppression, and is associated with significant morbidity. Pharmacogenetic
      testing may predict those with a high risk of EFV discontinuation, and therefore
      should be considered in patients in whom initiation of EFV based ART is being
      considered. FUNDING: Funded by NIH.

PMID- 26288844
TI  - Structural analysis of the unmutated ancestor of the HIV-1 envelope V2 region
      antibody CH58 isolated from an RV144 vaccine efficacy trial vaccinee.
AB  - Human monoclonal antibody CH58 isolated from an RV144 vaccinee binds at Lys169 of
      the HIV-1 Env gp120 V2 region, a site of vaccine-induced immune pressure. CH58
      neutralizes HIV-1 CRF_01 AE strain 92TH023 and mediates ADCC against CD4 + T cell
      targets infected with CRF_01 AE tier 2 virus. CH58 and other antibodies that bind
      to a gp120 V2 epitope have a second light chain complementarity determining
      region (LCDR2) bearing a glutamic acid, aspartic acid (ED) motif involved in
      forming salt bridges with polar, basic side amino acid side chains in V2. In an
      effort to learn how V2 responses develop, we determined the crystal structures of
      the CH58-UA antibody unliganded and bound to V2 peptide. The structures showed an
      LCDR2 structurally pre-conformed from germline to interact with V2 residue
      Lys169. LCDR3 was subject to conformational selection through the affinity
      maturation process. Kinetic analyses demonstrate that only a few contacts were
      responsible for a 2000-fold increase in KD through maturation, and this effect
      was predominantly due to an improvement in off-rate. This study shows that
      preconformation and preconfiguration can work in concert to produce antibodies
      with desired immunogenic properties. 

PMID- 26288845
TI  - Matrix Metalloproteinase Mediated Type I Collagen Degradation - An Independent
      Risk Factor for Mortality in Women.
AB  - Chronic fibro-proliferative diseases are associated with nearly 45% of all deaths
      in the developed world. Matrix metalloproteinase (MMP) mediated remodeling of the
      extracellular matrix (ECM) plays an important role in disease development.
      Degradation of type I collagen is considered having a major role in this matter.
      C1M is a biomarker measuring type I collagen degradation fragments in blood. The
      aim of the current study was to investigate whether MMP mediated type I collagen
      degradation (C1M) was predictive of mortality in a large prospective cohort of
      Danish women aged 48-89 (n = 5855). Subjects with high serum C1M showed
      significant increased mortality. The adjusted three year HR was 2.02 [95% CI:
      1.48-2.76] for all-cause mortality, 2.32 [95% CI: 1.51-3.56] for cancer and 1.77
      [95% CI: 0.98-3.17] for cardiovascular diseases. The adjusted nine year HR was
      1.50 [95% CI: 1.28-1.75] for all-cause mortality, 1.49 [95% CI: 1.16-1.90] for
      cancer and 1.69 [95% CI: 1.27-2.24] for cardiovascular diseases. High MMP
      mediated type I collagen degradation was associated with increased mortality.
      Subjects with high C1M had a 2-fold increase in mortality compared to subjects
      with low levels of this collagen degradation product. 

PMID- 26288847
TI  - TYK2 Promoter Variant and Diabetes Mellitus in the Japanese.
AB  - BACKGROUND: Recently, natural mutation of Tyrosine kinase 2 (Tyk2) gene has been
      shown to determine susceptibility to murine virus-induced diabetes. In addition,
      a previous human genome-wide study suggested the type 1 diabetes (T1D)
      susceptibility region to be 19p13, where the human TYK2 gene is located
      (19p13.2). METHODS: Polymorphisms of TYK2 gene at the promoter region and exons
      were studied among 331 healthy controls, and 302 patients with T1D and 314 with
      type 2 diabetes (T2D) in the Japanese. FINDINGS: A TYK2 promoter haplotype with
      multiple genetic polymorphisms, which are in complete linkage disequilibrium,
      named TYK2 promoter variant, presenting decreased promoter activity, is
      associated with an increased risk of not only T1D (odds ratio (OR), 2.4; 95%
      confidence interval (CI), 1.2 to 4.6; P = 0.01), but also T2D (OR, 2.1; 95% CI,
      1.1 to 4.1; P = 0.03). The risk is high in patients with T1D associated with flu
      like syndrome at diabetes onset and also those without anti-glutamic acid
      decarboxylase autoantibody. INTERPRETATION: The TYK2 promoter variant is
      associated with an overall risk for diabetes, serving a good candidate as a virus
      induced diabetes susceptibility gene in humans. FUNDING: Ministry of Education,
      Culture, Sports, Science and Technology and of Health, Labor and Welfare of
      Japan.

PMID- 26288846
TI  - Sustained Brown Fat Stimulation and Insulin Sensitization by a Humanized
      Bispecific Antibody Agonist for Fibroblast Growth Factor Receptor 1/betaKlotho
      Complex.
AB  - Dissipating excess calories as heat through therapeutic stimulation of brown
      adipose tissues (BAT) has been proposed as a potential treatment for obesity
      linked disorders. Here, we describe the generation of a humanized effector-less
      bispecific antibody that activates fibroblast growth factor receptor (FGFR)
      1/betaKlotho complex, a common receptor for FGF21 and FGF19. Using this molecule,
      we show that antibody-mediated activation of FGFR1/betaKlotho complex in mice
      induces sustained energy expenditure in BAT, browning of white adipose tissue,
      weight loss, and improvements in obesity-associated metabolic derangements
      including insulin resistance, hyperglycemia, dyslipidemia and hepatosteatosis. In
      mice and cynomolgus monkeys, FGFR1/betaKlotho activation increased serum high
      molecular-weight adiponectin, which appears to contribute over time by enhancing
      the amplitude of the metabolic benefits. At the same time, insulin sensitization
      by FGFR1/betaKlotho activation occurs even before the onset of weight loss in a
      manner that is independent of adiponectin. Together, selective activation of
      FGFR1/betaKlotho complex with a long acting therapeutic antibody represents an
      attractive approach for the treatment of type 2 diabetes and other obesity-linked
      disorders through enhanced energy expenditure, insulin sensitization and
      induction of high-molecular-weight adiponectin. 

PMID- 26288848
TI  - Reduced Lysosomal Acid Lipase Activity in Adult Patients With Non-alcoholic Fatty
      Liver Disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is characterized by intra-hepatic fat
      accumulation and mechanisms involved in its pathogenesis are not fully explained.
      Lysosomal Acid Lipase (LAL) is a key enzyme in lipid metabolism. We investigated
      its activity in patients with fatty liver. LAL activity (nmol/spot/h) was
      measured in 100 adult healthy subjects (HS) and in 240 NAFLD patients. A sub
      analysis on 35 patients with biopsy-proven non-alcoholic steatohepatitis (NASH)
      was performed. Median LAL activity was 1.15 (0.95-1.72) in HS. It was
      significantly reduced in NAFLD [0.78 (0.61-1.01), p < 0.001 vs. HS]. A further
      reduction was observed in the subgroup of NASH [0.67 (0.51-0.77), p < 0.001 vs.
      HS]. Patients with LAL activity below median had higher values of serum total
      cholesterol (p < 0.05) and LDL-c (p < 0.05), and increased serum liver enzymes
      (ALT, p < 0.001; AST, p < 0.01; GGT, p < 0.01). At multivariable logistic
      regression analysis, factors associated with LAL activity below median were ALT
      (OR: 1.018, 95% CI 1.004-1.032, p = 0.011) and metabolic syndrome (OR: 2.551, 95%
      CI 1.241-5.245, p = 0.011), whilst statin use predicted a better LAL function
      (OR: 0.464, 95% CI 0.248-0.866, p = 0.016). Our findings suggest a strong
      association between impaired LAL activity and NAFLD. A better knowledge of the
      role of LAL may provide new insights in NAFLD pathogenesis. 

PMID- 26288849
TI  - Ocular pseudoexfoliation syndrome and life span.
AB  - BACKGROUND: To compare life span of persons with and without ocular
      pseudoexfoliation syndrome (PES). METHODS: The study is based on an
      epidemiological survey conducted in Sor-Trondelag county, Norway, in 1985-86. All
      inhabitants over 64 years of age (2109 individuals) were invited. Mortality
      information was obtained from The Norwegian Institute of Public Health in 2014,
      by which time 99% of the participants were deceased. RESULTS: When adjusting for
      age and gender, life span was not statistically different in persons with and
      without PES. Following the diagnosis of PES, patients' survival was up to, and
      beyond, 30 years. CONCLUSIONS: Our observations suggest that, despite all the
      systemic aberrations reported in persons with ocular PES, none or only marginal
      functional changes are caused in extraocular organs and tissues. The present
      study supports the notion that systemic PES is not a life-threatening condition.

PMID- 26288850
TI  - Predictors of resolution in navigated patients with abnormal cancer screening
      tests.
AB  - BACKGROUND: Patient navigation has been effective in improving cancer care, yet
      little is known about what predicts timely outcomes in navigated patients.
      OBJECTIVE: To identify predictors of resolution of abnormal cancer screening
      tests in patients who received navigation. METHODS: We examined data on patients
      with abnormal breast (n = 256) or cervical (n = 150) screening tests or symptoms
      who received navigation as part of the Ohio Patient Navigator Research Program
      during 2007-2010. We used multivariable Cox proportional hazards regression
      models to identify predictors of time to resolution (ie, when a patient's
      clinical abnormality or abnormal screening test was determined to be a benign
      condition or a cancer diagnosis). RESULTS: The median time to resolution was 183
      days for navigated patients with breast abnormalities and 172 days for navigated
      patients with cervical abnormalities. In patients with breast abnormalities,
      those who reported at least 1 barrier to care during navigation (HR, 0.66; 95%
      CI, 0.51-0.86) or higher perceived stress (HR, 0.90; 95% CI, 0.82-0.98) had
      slower resolution. Among patients with cervical abnormalities, those who reported
      at least 1 barrier to care during navigation had slower resolution (HR, 0.62; 95%
      CI, 0.42-0.91). Patients with cervical abnormalities had faster resolution if
      they had private health insurance, but this effect was present only in younger
      women (interaction ?? = .003). LIMITATIONS: Unknown generalizability of results
      because patients were female and from clinics in central Ohio. CONCLUSIONS:
      Several variables predicted whether patient navigation led to faster resolution,
      and predictors differed somewhat by disease site. Results will be useful in
      improving current patient navigation programs and designing future programs.

PMID- 26288851
TI  - Contribution of rotational diffusivity towards the transport of antigens in
      heterogeneous immunosensors.
AB  - Higher capture efficiency in heterogeneous immunosensors is desirable for the
      detection of cancer biomarkers at low concentrations. The process of the capture
      of these antigens is transport limited since the rates of antigen/antibody
      reactions are faster. In the case of non-flow systems, diffusive transport has
      contributions from both translational and rotational phenomena. Since the
      contribution of the rotational diffusivity is comparatively less explored in the
      literature, we have studied the same for three antigens - bovine serum albumin
      (BSA), prostate specific antigen (PSA) and C-reactive proteins (CRP). We
      quantified the rotational diffusivities using the time resolved fluorescence
      anisotropy method, and further quantified the contribution of the rotational
      diffusivities to the overall diffusivity of the antigens, and also studied the
      effect of the process parameters - temperature and pH of the solution. With an
      increase in temperature, the rotational diffusivity increased showing Arrhenius
      dependence while with the variation of pH, it showed a non-monotonic behavior
      having maxima closer to the isoelectric point of the corresponding antigens. This
      interesting behavior of the pH values could be attributed to lesser electro
      viscous effects when the antigen molecule is neutral around its isoelectric
      point. The optimization of the pH and temperature for the immunosensors could be
      utilized to design efficient immunosensors.

PMID- 26288852
TI  - Label-free detection of Cu(II) in a human serum sample by using a prion protein
      immobilized FET sensor.
AB  - We have developed a field effect transistor (FET) sensor to sensitively detect
      copper ions (Cu(2+)) in a human serum (HS) sample for promising health-care
      diagnosis. By utilizing a Cu(2+)-binding prion protein that was immobilized on
      the FET gate surface, such an FET sensor can provide a simple, label free and
      highly selective performance, even in HS samples. We demonstrated the sensitivity
      of the sensor at the nanomolar level, 0-100 nM, which is very useful for the
      detection range of Cu(2+) deficiency in practical applications. 

PMID- 26288853
TI  - Multi-stage, charge conversional, stimuli-responsive nanogels for therapeutic
      protein delivery.
AB  - A boronate ester crosslinked zwitterionic nanogel (NGCA) with ATP/pH-sensitivity
      has been developed with an inverse nanoprecipitation technique to achieve a two
      stage charge conversion that responds to tumor extracellular conditions (pH 6.5
      6.8) and an intracellular acidic environment (pH 5-6). Cationic cytochrome C
      (CC), a therapeutic protein, has been encapsulated into NGCA through inverse
      nanoprecipitation via electrostatic interactions to form protein-loaded nanogel
      (NGCA-CC). By adjusting the ratio of the amino and carboxyl groups in the
      nanogels, negatively charged nanogels that are safer under physiological
      conditions (pH 7.4) can convert their surface charge to positive at tumor
      extracellular pH, which enhance their cellular uptake efficiency. The citraconic
      amide formed from citraconic anhydride and amine can be cleaved in the
      intracellular acidic organelles to expose more amino groups and facilitate
      endosomal escape. The release of CC is accelerated in the presence of 5 mM ATP or
      under acidic conditions. Confocal laser scanning microscopy (CLSM) and flow
      cytometry have shown that NGCA-CC's cell uptake is higher at pH 6.5 than at pH
      7.4. MTT and real-time cell analysis (RTCA) have illustrated that there is more
      toxicity at pH 6.5 than at pH 7.4. The apoptosis process induced by CC was
      determined by flow cytometry. 

PMID- 26288854
TI  - A biosensor for the detection of single base mismatches in microRNA.
AB  - Graphene oxide quenches fluorescence corresponding to only a mismatched target
      due to selective denaturing of the thermo-unstable duplex composed of probe
      peptide nucleic acid and single base mismatched target RNA and thus, the
      fluorescence signal only from perfectly matched target RNA is measured. 

PMID- 26288855
TI  - Jadomycins, put a bigger ring in it: isolation of seven- to ten-membered ring
      analogues.
AB  - We report the production, isolation, and characterization of jadomycins with
      seven-, nine-, and ten-membered E-rings, all of which are unique natural product
      ring scaffolds. This significantly expands the scope of a non-enzymatic
      biosynthetic step in jadomycin biosynthesis in order to produce novel natural
      products. 

PMID- 26288856
TI  - Remarkable reactivity of a rhodium(I) boryl complex towards CO2 and CS2:
      isolation of a carbido complex.
AB  - The activation of CO2, CS2 as well as of PhNCO at [Rh(Bpin)(PEt3)3] led to C=X
      bond cleavage and the formation of {RhXBpin} species (X = O, S, N). Treatment of
      the boryl complex [Rh(Bpin)(PEt3)3] with 0.5 equivalents of CS2 resulted in the
      fragmentation of CS2 and the formation of the remarkable MU-carbido complex trans
      [Rh2(MU-C)(SBpin)2(PEt3)4].

PMID- 26288857
TI  - Concise synthesis of (+/-)-Lingzhiol via epoxy-arene cyclization.
AB  - Concise synthesis of (+/-)-Lingzhiol has been achieved. The key reaction involves
      one-step construction of a 5/5/6/6 tetra-ring backbone of Lingzhiol via epoxy
      arene cyclization. 

PMID- 26288858
TI  - Amphiphilic hollow porous shell encapsulated Au@Pd bimetal nanoparticles for
      aerobic oxidation of alcohols in water.
AB  - This work describes the design, synthesis and analysis of an amphiphilic hollow
      mesoporous shell encapsulating catalytically active Au@Pd bimetal nanoparticles.
      The particles exhibited excellent catalytic activity and stability in the aerobic
      oxidation of primary and secondary alcohols to their corresponding aldehydes or
      ketones in water when using air as an oxidizing agent under atmospheric pressure.

PMID- 26288859
TI  - Differentially functionalized acyclic cucurbiturils: synthesis, self-assembly and
      CB[6]-induced allosteric guest binding.
AB  - We report the synthesis of mono- and difunctionalized acyclic cucurbit[n]uril
      type containers (1HA, 1HDA, 2HDA) which bear hexylammonium and hexanediammonium
      arms. The intra- and intermolecular assembly processes of 1HA, 1HDA, 2HDA as well
      as the ability of CB[n] to trigger allosteric host-guest binding toward guests 9
      11 are presented.

PMID- 26288860
TI  - [Comparative observation of diffuse radiation in Qianyanzhou during the spring of
      2012].
AB  - Global radiation and diffuse radiation were measured from March to June of 2012
      in Qianyanzhou Experimental Station of Red Soil and Hilly Land, Chinese Academy
      of Sciences by ising three types of pyranometers, including CMP11 attached with a
      shadow ring, SPN1 and RSR3, which were placed in parallel. The observations
      showed that both global radiation and diffuse radiation measured by these
      pyranometers had a good linear correlation. The global radiation measured by SPN1
      and RSR3 was respectively 3. 0% and 20.5% lower than that measured by the CMP 11.
      The diffuse radiation measured by SPN1 and RSR3. was respectively 5.5% and 7.9%
      lower of than that measured by the CMP11. Under the sunny, cloudy and overcast
      conditions, the daily variations of diffuse radiation measured by the three
      pyranometers were similar, and hence, the diffuse radiation values at a specific
      solar elevation angle measured by the different pyranometers were also similar.
      There was difference in daily accumulative diffuse radiation measured by the
      different pyranometers. Monthly diffuse fractions of March, April and May were
      0.56, 0.59 and 0.70, respectively. In the subtropical area of southern China, the
      diffuse radiation accounted for a relatively large proportion of the global solar
      radiation and varied considerably over time. It is necessary to conduct long-term
      continuous measurements to capture the variability of diffuse radiation over
      different underlying surfaces.

PMID- 26288861
TI  - [The changes of vascular active substances in pulmonary embolism rats and a
      comparative study of anticoagulant drugs].
AB  - OBJECTIVE: To establish the rat model of acute pulmonary embolism, and study the
      changes of vascular active substances in pulmonary embolism rats, and investigate
      the interventive effect of anticoagulant drugs on vascular active substances.
      METHODS: One hundred and twenty-eight rats were randomly divided into four
      groups: control group, model group, low-molecular-weight heparin and warfarin
      treated group and rivaroxaban-treated group (n = 32 in each group). The method of
      autologous thrombosis was used to establish the animal model of acute pulmonary
      embolism. The animals were treated with saline or different anticoagulant drugs.
      The physiological and biochemical parameters were detected at different time
      points after embolization. The rats were killed after embolism of 24 h, 3 d, 5 d
      or 1 week respectively and the pathologic samples of lung tissues were collected
      to analyze the pulmonary pathological changes in different groups. RESULTS: Rats
      in embolization group after blood clots injection showed shortness of breath,
      oral cyanosis; quicken heart rates and other symptoms. All embolization groups
      had pulmonary hypertension, the levels of type B natriuretic peptide (BNP) were
      increased significantly. The ratio of endothelin-1 (ET-1)/NO and thromboxane
      (TXB2) and prostacyclin (6-k-PGFla) were abnormal. After treated with effective
      anticoagulant drugs, the levels of BNP, ET-1, NO, TXB2 and 6-k-PGF1a were tended
      to the normal levels in the control group. The pulmonary hypertensions were
      gradually decreased. The efficacy of rivaroxaban on pulmonary embolism was the
      same as that of the low molecular weight heparin or warfarin. CONCLUSION:
      Anticoagulation therapy can effectively improve endothelial function after
      pulmonary embolism, reduce pulmonary hypertension, and revise the increased BNP
      levels to normal levels. The efficacy of rivaroxaban is not inferior to that of
      low molecular weight heparin and warfarin.

PMID- 26288862
TI  - [Nitrification of biological soil crusts and soil system during drought process
      and its response to temperature and moisture: A case study in the Shapotou
      region, Northwest China].
AB  - Two types of soil covered by biological soil crusts (BSCs) , i.e. moss and algae,
      and moving sand in the natural vegetation area at the southeast fringe of the
      Tengger Desert were collected intactly. They were incubated continuously for 20
      days under two different temperatures (15 degrees C and 25 degrees C) and
      moistures (10% and 25%) condition in the laboratory, and soil NO3(-)-N contents
      were measured after 1, 2, 5, 8, 12, 20 days of incubation and net nitrification
      rate was evaluated during dehydration. The results showed that NO3(-)-N content
      of the moss-covered soil (2.29 mg x kg(-1)) was higher than that of the algae
      covered soil (1.84 mg x kg(-1)) and sand (1.59 mg x kg(-1)). Net nitrification
      rate of the three soil types ranged from -3.47 to 2.97 mg x kg(-1) x d(-1). For
      the moss-covered soil and algae-covered soil at 10% and 25% moisture levels, the
      net nitrification rates at 15 degrees C were 75.1%, 0.7% and 99.1%, 21.3% higher
      than those at 25 degrees C, respectively. Also, the net nitrification rates at 15
      degrees C and 10% moisture levels were 193.4% and 107.3% higher than those at 25
      degrees C and 25% moisture levels, respectively. The results suggested that
      regardless of soil moisture increasing or decreasing under the global warming
      senior, the net nitrification rate of BSCs-soil system in the desert would
      probably be limited to some extent during drought process.

PMID- 26288864
TI  - [Lymphoepithelial Cyst of the Pancreas].

PMID- 26288865
TI  - [Efficacy and Safety of an Oral SMAD7 Antisense Drug for Active Crohn's Disease].

PMID- 26288866
TI  - Primary Care Providers' Views of Recent Trends in Health Care Delivery and
      Payment. Findings from the Commonwealth Fund/Kaiser Family Foundation 2015
      National Survey of Primary Care Providers.
AB  - A new survey from The Commonwealth Fund and The Kaiser Family Foundation asked
      primary care providers--physicians, nurse practitioners, and physician assistants
      -about their experiences with and reactions to recent changes in health care
      delivery and payment. Providers' views are generally positive regarding the
      impact of health information technology on quality of care, but they are more
      divided on the increased use of medical homes and accountable care organizations.
      Overall, providers are more negative about the increased reliance on quality
      metrics to assess their performance and about financial penalties. Many
      physicians expressed frustration with the speed and administrative burden of
      Medicaid and Medicare payments. An earlier brief focused on providers'
      experiences under the ACA's coverage expansions and their opinions about the law.

PMID- 26288867
TI  - [The Epidemiology and Surgical Indication of Epiretinal Membrane].

PMID- 26288868
TI  - [Prevalence of Epiretinal Membrane Using Optical Coherence Tomography].
AB  - PURPOSE: To investigated the prevalence and risk factors of epiretinal membrane
      (ERM). SUBJECTS AND METHOD: Five hundred eyes of 500 patients (202 men and 298
      women, average age 74.9), who underwent cataract surgery in Otsuka Eye Clinic one
      or two months before the survey, were examined using spectral-domain optical
      coherence tomography (OCT). RESULTS: ERMs were observed in 43 eyes (8.6%) and 31
      eyes (6.2%) were diagnosed as idiopathic ERM. Idiopathic ERM was significantly
      associated with age, but not with gender, best-corrected visual acuity after
      cataract surgery or diabetes. Only 4.8 percent of idiopathic ERM patients had
      subjective symptoms detected by the Amsler chart. CONCLUSIONS: The prevalence of
      ERM was 8.6% and of idiopathic ERM 6.2%. The most prevalent risk factor of
      idiopathic ERM was aging.

PMID- 26288870
TI  - [Comparison of Retinal Detachment Associated with Atopic Dermatitis with that of
      a Blunt Trauma].
AB  - PURPOSE: Retinal detachment associated with atopic dermatitis has been reported
      to have several similarities to retinal detachment with blunt trauma both in
      location and types of retinal breaks. To clarify the difference between these two
      types of retinal detachment, the clinical features of retinal detachment
      associated with atopic dermatitis to those with blunt trauma were compared.
      METHOD: Among phakic eyes of rhegmatogenous retinal detachment which underwent
      surgery in our clinic between 2006 and 2011, 51 eyes of 41 cases of retinal
      detachment associated with atopic dermatitis (Atopy group) and 53 eyes of 51
      cases of retinal detachment with blunt trauma (Trauma group) were compared.
      RESULTS: In the Atopy group, the patients were younger, and the incidence of
      cataracts and bilateral detachment were more frequent. In the Trauma group, the
      occurence was more frequent in men and associated vitreous hemorrhage and iritis
      were more frequent. Shallow retinal detachments and ciliary breaks located at the
      superotemporal quadrant were more frequent in the Atopy group and bullous
      detachments and retinal breaks located at the superonasal quadrant were more
      frequent in the trauma group. Oral dialysis and ciliary breaks were frequent in
      both groups. The initial retinal reattachment rates were similar between both
      groups but the final reattachment rate was worse in the trauma group.
      CONCLUSIONS: Retinal detachment associated with atopic dermatitis had many
      similarities to the detachment with blunt trauma in types of retinal breaks.
      However, it was distinct in featuring higher incidence of bilateral retinal
      detachment, cataracts, and ciliary breaks at the superotemporal quadrant.

PMID- 26288869
TI  - [Variations of Intraocular Pressure with the Variations of Measurement
      Environment in Patients with Primary Open Angle Glaucoma].
AB  - OBJECTIVES: To examine the variations in intraocular pressure (IOP) occuring upon
      changes in clinical premises' relocation in patients with primary open angle
      glaucoma (POAG). SUBJECTS AND METHODS: Two hundred and twenty-four eyes of 224
      patients with POAG were examined. We compared the IOP values measured with an
      identical noncontact tonometer (NCT) (CT-90A) obtained on May 2014 (IOP514)
      before the clinical premises' relocation, and those obtained on June (IOP614),
      July or August (IOP7814) 2014 after relocation. To examine the systematic errors
      of the NCT, Bland-Altman plot analysis was applied. RESULTS: IOP614 (12.2 +/- 2.7
      mmHg) and IOP7814 (12.1 +/- 2.7mmHg) were significantly lower than IOP514 (13.1
      +/- 2.9 mmHg) (p < 0.001). IOP614 was also lower than IOP514, both in the beta
      blocker and prostaglandin analogue groups. When these values were adjusted using
      those obtained one year before the clinical relocation to take seasonal
      variations into consideration, IOP after relocation was lower than IOP before
      relocation (p < 0.001). Proportional bias was not detected (r = 0.082; p =
      0.999). CONCLUSION: There was a variation in IOP determined by the identical
      noncontact tonometer between before and after the clinical premises' relocation
      in patients with POAG.

PMID- 26288871
TI  - [EDITOR'S NOTE].

PMID- 26288872
TI  - Joint Commission Leaders Author JAMA Viewpoint on High Reliability Strategies.

PMID- 26288873
TI  - Expanded Requirement for Perinatal Care Measure Set Reporting.

PMID- 26288874
TI  - Joint Commission Joins White House Effort to Reduce Antibiotic Overuse.

PMID- 26288875
TI  - New Online Publications Focus on Respiratory Protection for Health Care Workers.

PMID- 26288876
TI  - The National Pediatric Readiness Project. Ensuring Appropriate ED Care for
      Children.

PMID- 26288877
TI  - Revised Laboratory Requirements: Immunohistochemistry and Microbiology.

PMID- 26288878
TI  - Revisions to Outpatient Record Review. Requirements for Critical Access
      Hospitals.

PMID- 26288879
TI  - Revised Requirements for Nursing Care Centers.

PMID- 26288880
TI  - [Neutron Dosimetry System Using CR-39 for High-energy X-ray Radiation Therapy].
AB  - Neutrons are produced during radiation treatment by megavolt X-ray energies.
      However, it is difficult to measure neutron dose especially just during the
      irradiation. Therefore, we have developed a system for measuring neutrons with
      the solid state track detector CR-39, which is free from the influence of the X
      ray beams. The energy spectrum of the neutrons was estimated by a Monte Carlo
      simulation method, and the estimated neutron dose was corrected by the
      contribution ratio of each energy. Pit formation rates of CR-39 ranged from 2.3 x
      10(-3) to 8.2 x 10(-3) for each detector studied. According to the estimated
      neutron energy spectrum, the energy values for calibration were 144 keV and
      515keV, and the contribution ratios were approximately 40:60 for 10 MV photons
      and 20:70 for photons over 15 MV. Neutron doses measured in the center of a high
      energy X-ray field were 0.045 mSv/Gy for a 10 MV linear accelerator and 0.85
      mSv/Gy for a 20 MV linear accelerator. We successfully developed the new neutron
      dose measurement system using the solid track detector, CR-39. This on-time
      neutron measurement system allows users to measure neutron doses produced in the
      radiation treatment room more easily.

PMID- 26288881
TI  - [Initiatives toward Appropriate Justification and Optimization].

PMID- 26288882
TI  - [Primary Standard of Absorbed Dose to Water in High-energy Photon Beam
      Irradiation].
AB  - With the aim of improving the accuracy of photon dosimetry, the primary standard
      of absorbed dose to water for high-energy photon beams had been established using
      a graphite calorimeter. The relative expanded uncertainty (k = 2) of the
      calibration coefficient of absorbed dose to water for high-energy photon beams is
      0.8%. The National Metrology Institute of Japan has launched a calibration
      service for high-energy photon beams in terms of absorbed dose to water in
      November 2013.

PMID- 26288883
TI  - [Series (3). The Basis of Medical Particle Accelerators-Synchrotron].

PMID- 26288885
TI  - Epileptic Seizure Detection and Prediction Based on Continuous Cerebral Blood
      Flow Monitoring--a Review.
AB  - Epilepsy is the third most common neurological illness, affecting 1% of the
      world's population. Despite advances in medicine, about 25 to 30% of the patients
      do not respond to or cannot tolerate the severe side effects of medical
      treatment, and surgery is not an option for the majority of patients with
      epilepsy. The objective of this article is to review the current state of
      research on seizure detection based on cerebral blood flow (CBF) data acquired by
      thermal diffusion flowmetry (TDF), and CBF-based seizure prediction. A discussion
      is provided on the applications, advantages, and disadvantages of TDF in
      detecting and localizing seizure foci, as well as its role in seizure prediction.
      Also presented are an overview of the present challenges and possible future
      research directions (along with methodological guidelines) of the CBF-based
      seizure detection and prediction methods.

PMID- 26288884
TI  - A Computer-aided Method for Improving the Reliability of Lenke Classification for
      Scoliosis.
AB  - Classification of the spinal curve pattern is crucial for assessment and
      treatment of scoliosis. We developed a computer-aided system to improve the
      reliability of three components of the Lenke classification. The system semi
      automatically measured the Cobb angles and identified the apical lumbar vertebra
      and its pedicles on digitized radiographs. The system then classified the curve
      type, lumbar modifier, and thoracic sagittal modifier of the Lenke classification
      based on the computerized measurements and identifications. The system was tested
      by five operators for 62 scoliotic cases. The kappa statistic was used to assess
      the reliability. With the aid of computer, the average intra- and interobserver
      kappa values were improved to 0.89 and 0.81 for the curve type, to 0.83 and 0.81
      for the lumbar modifier, and to 0.94 and 0.92 for the sagittal modifier of the
      Lenke classification, respectively, relative to the classification by two of the
      operators without the aid of computer. Results indicate that the computerized
      system can improve reliability for all three components of the Lenke
      classification.

PMID- 26288886
TI  - Backrest Shape Affects Head-Neck Alignment and Seated Pressure.
AB  - Unstable back support against gravity results in a forward head posture and
      contributes to buttocks pressure ulcers. However, the association between these
      health problems and a wheelchair backrest is unclear. Our newly developed
      wheelchair (N-WC) supports the back of the pelvis and thorax from obliquely
      underneath. The purpose of this study was to investigate the effect of different
      backrest shapes on head-neck alignment and seated pressure. Data from 28 healthy
      subjects were analyzed. Outcome measures were head-neck alignment angles, support
      angles of the backrest, and pressure distributions on the supporting surfaces.
      Compared with a typical wheelchair that has a flat backrest, the seat pressure
      decreased and the center of pressure was located in the middle of both the seat
      and backrest in the N-WC. Moreover, the head-neck alignment when seated in the N
      WC was upright. These results highlight the importance of the shape of the
      wheelchair backrest.

PMID- 26288887
TI  - Mechanical Model of Traditional Thai Massage for Integrated Healthcare.
AB  - In this study, a mechanical model was developed, aiming to provide standardized
      and programmable traditional Thai massage (TTM) therapy to patients. The TTM was
      modeled and integrated into a mechanical hand (MH) system, and a prototype
      massage chair was built and tested for user satisfaction. Three fundamental
      principles of Thai massage were integrated: pull, press, and pin. Based on these
      principles, the mechanics of Thai massage was studied and a mathematical model
      was developed to describe the dynamics and conditions for the design and
      prototyping of an MH. On average, it was found that users were satisfied with the
      treatment and felt that the treatment was similar to that performed by human
      hands. According to the interview results, users indicated that they were likely
      to utilize the MH as an alternative to traditional massage. Therefore, integrated
      TTM with an MH may help healthcare providers deliver standardized, programmable
      massage therapy to patients as opposed to variable, inconsistent human massage.

PMID- 26288889
TI  - Grid Patient Appointment Template Design to Improve Scheduling Effectiveness.
AB  - Current outpatient delivery systems have been problematic in their ability to
      effectively schedule appointments and grant patients access to care. A better
      appointment system has demonstrated improvement on these issues. The objective of
      this study is to develop a grid appointment system to further improve the
      scheduling flexibility by determining the minimum length of appointment slots
      that optimizes the total costs of patient waiting, physician idling, and
      overtime. This minimum length is used for the patient type requiring the least
      amount of treatment time such as return visit (RV), and multiplications of the
      minimum length are for patient types with longer treatment such as new patients
      (NP). The results indicated that the proposed grid system adjusts to demand
      changes at least 15% more cost-effective when grouping two RVs into an NP or
      dividing an NP into two RVs compared to the base-line scheduling approaches that
      build around the mean treatment time.

PMID- 26288888
TI  - Usability of a Wearable Camera System for Dementia Family Caregivers.
AB  - Health care providers typically rely on family caregivers (CG) of persons with
      dementia (PWD) to describe difficult behaviors manifested by their underlying
      disease. Although invaluable, such reports may be selective or biased during
      brief medical encounters. Our team explored the usability of a wearable camera
      system with 9 caregiving dyads (CGs: 3 males, 6 females, 67.00 +/- 14.95 years;
      PWDs: 2 males, 7 females, 80.00 +/- 3.81 years, MMSE 17.33 +/- 8.86) who recorded
      79 salient events over a combined total of 140 hours of data capture, from 3 to 7
      days of wear per CG. Prior to using the system, CGs assessed its benefits to be
      worth the invasion of privacy; post-wear privacy concerns did not differ
      significantly. CGs rated the system easy to learn to use, although cumbersome and
      obtrusive. Few negative reactions by PWDs were reported or evident in resulting
      video. Our findings suggest that CGs can and will wear a camera system to reveal
      their daily caregiving challenges to health care providers.

PMID- 26288890
TI  - Scheduling Patients' Appointments: Allocation of Healthcare Service Using
      Simulation Optimization.
AB  - In the service industry, scheduling medical procedures causes difficulties for
      both patients and management. Factors such as fluctuations in customer demand and
      service time affect the appointment scheduling systems' performance in terms of,
      for example, patients' waiting time, idle time of resources, and total
      cost/profits. This research implements four appointment scheduling policies,
      i.e., constant arrival, mixed patient arrival, three-section pattern arrival, and
      irregular arrival, in an ultrasound department of a hospital in Taiwan. By
      simulating the four implemented policies' optimization procedures, optimal or
      near-optimal solutions can be obtained for patients per arrival, patients' inter
      arrival time, and the number of the time slots for arrived patients. Furthermore,
      three objective functions are tested, and the results are discussed. The
      managerial implications and discussions are summarized to demonstrate how
      outcomes can be useful for hospital managers seeking to allocate their healthcare
      service capacities.

PMID- 26288891
TI  - Foreword: Introducing innovations in an old area of care.

PMID- 26288892
TI  - Compression bandaging for chronic oedema: applying science to reality.
AB  - Among other risk factors, chronic venous insufficiency predisposes an individual
      to chronic oedema. The use of compression bandaging in the intensive phase of
      treatment is indicated to reduce distortion, lymphorrhoea, and achieve wound
      healing. When applying a compression bandage, it is essential that the clinician
      considers the laws that underpin the theory of compression. Owing to the physical
      properties of the bandages, the use of inelastic compression is favoured for the
      management of chronic oedema, in view of the high static stiffness index achieved
      on application. It is essential that the bandaging regime is individualised to
      meet the specific needs of the patient. This includes the frequency of bandage
      change, while considering the extent of oedema reduction and holistic needs of
      the patient.

PMID- 26288893
TI  - Using specialist bandage techniques to improve outcomes.
AB  - Chronic oedema is a condition that can become more complex to manage if allowed
      to progress. With the risk of chronic oedema increasing with age, complex
      presentations may become more commonplace as projections indicate an ageing
      population. A full holistic assessment is vital, taking into account venous,
      lymphatic and arterial elements of a vascular assessment, in order to determine
      the underlying disease process. Competency-based techniques for the application
      for below-knee and thigh-length application of inelastic cohesive compression
      exist and support clinicians in the successful management of chronic oedema. In
      cases of severe or complex chronic oedema, the specialist clinician can adopt
      strategies to adapt standard application to achieve volume reduction, shape, and
      tissue improvement.

PMID- 26288894
TI  - Case reports.

PMID- 26288895
TI  - Effective management of lower limb lymphoedema using Actico and Rosidal soft.

PMID- 26288896
TI  - Managing chronic oedema and associated ulceration and lymphorrhoea using Actico
      specialist bandaging techniques.

PMID- 26288897
TI  - Adapting the Crossmodal Congruency Task for Measuring the Limits of Visual
      Tactile Interactions Within and Between Groups.
AB  - The crossmodal congruency task (CCT) is a commonly used paradigm for measuring
      visual-tactile interactions and how these may be influenced by discrepancies in
      space and time between the tactile target and visual distractors. The majority of
      studies which have used this paradigm have neither measured, nor attempted to
      control, individual variability in unisensory (tactile) performance. We have
      developed a version of the CCT in which unisensory baseline performance is
      constrained to enable comparisons within and between participant groups.
      Participants were instructed to discriminate between single and double tactile
      pulses presented to their dominant hand, at their own approximate threshold
      level. In Experiment 1, visual distractors were presented at -30 ms, 100 ms, 200
      ms and 400 ms stimulus onset asynchronies. In Experiment 2, ipsilateral visual
      distractors were presented 0 cm, 21 cm, and 42 cm vertically from the target
      hand, and 42 cm in a symmetrical, contralateral position. Distractors presented 
      30 ms and 0 cm from the target produced a significantly larger congruency effect
      than at other time points and spatial locations. Thus, the typical limits of
      visual-tactile interactions were replicated using a version of the task in which
      baseline performance can be constrained. The usefulness of this approach is
      supported by the observation that tactile thresholds correlated with self
      reported autistic traits in this non-clinical sample. We discuss the suitability
      of this adapted version of the CCT for measuring visual-tactile interactions in
      populations where unisensory tactile ability may differ within and between
      groups.

PMID- 26288898
TI  - Introduction to the Special Issue on Multimodality of Early Sensory Processing:
      Early Visual Maps Flexibly Encode Multimodal Space.

PMID- 26288899
TI  - The Mechanisms of Size Constancy.
AB  - Size constancy is the result of cognitive scaling operations that enable us to
      perceive an object as having the same size when presented at different viewing
      distances. In this article, we review the literature on size and distance
      perception to form an overarching synthesis of how the brain might combine
      retinal images and distance cues of retinal and extra-retinal origin to produce a
      perceptual visual experience of a world where objects have a constant size. A
      convergence of evidence from visual psychophysics, neurophysiology,
      neuropsychology, electrophysiology and neuroimaging highlight the primary visual
      cortex (V1) as an important node in mediating size-distance scaling. It is now
      evident that this brain area is involved in the integration of multiple signals
      for the purposes of size perception and does much more than fulfil the role of an
      entry position in a series of hierarchical cortical events. We also discuss how
      information from other sensory modalities can also contribute to size-distance
      scaling and shape our perceptual visual experience.

PMID- 26288900
TI  - Where Is Size in the Brain of the Beholder?
AB  - Despite advances in our understanding of how the brain represents visual space,
      it remains unresolved how the subjective experience of an object's size arises.
      While responses in retinotopic cortex correlate with perceived size, this does
      not imply that those brain regions mediate perceived size differences. Here I
      describe how the percept of an object's size could be generated in the brain and
      outline unanswered questions that future research should seek to address.

PMID- 26288901
TI  - Plasticity, and Its Limits, in Adult Human Primary Visual Cortex.
AB  - There is an ongoing debate about whether adult human primary visual cortex (V1)
      is capable of large-scale cortical reorganization in response to bilateral
      retinal lesions. Animal models suggest that the visual neural circuitry maintains
      some plasticity through adulthood, and there are also a few human imaging studies
      in support this notion. However, the interpretation of these data has been
      brought into question, because there are factors besides cortical reorganization,
      such as the presence of sampling bias and/or the unmasking of task-dependent
      feedback signals from higher level visual areas, that could also explain the
      results. How reasonable would it be to accept that adult human V1 does not
      reorganize itself in the face of disease? Here, we discuss new evidence for the
      hypothesis that adult human V1 is not as capable of reorganization as in animals
      and juveniles, because in adult humans, cortical reorganization would come with
      costs that outweigh its benefits. These costs are likely functional and visible
      in recent experiments on adaptation--a rapid, short-term form of neural
      plasticity--where they prevent reorganization from being sustained over the long
      term.

PMID- 26288902
TI  - Bernhard Sabel and 'Residual Vision Activation Theory': a History Spanning Three
      Decades.
AB  - This review has the purpose of retracing the work of Professor Bernard Sabel and
      his group over the last 2-3 decades, in order to understand how they achieved
      formulation of the 'Residual Vision Activation Theory'. The methodology proposed
      is described, from the first studies in 1995 with High Resolution Perimetry
      requiring a six-months training period, to the new technologies, such as
      repetitive transorbital Alternating Current Stimulation, that require ten days of
      training. Vision restoration therapy has shown improvement in visual responses
      irrespective of age at the training, lesion aetiology and site of lesion. The
      hypothesis that visual training may induce network plasticity, improving neuronal
      networks in cortical and subcortical areas of both hemispheres, appears to be
      confirmed by recent studies including observation of the cerebral activity by
      fMRI and EEG. However, the results are quite variable and the mechanisms that
      influence cerebral activity are still unclear. The residual vision activation
      theory has been much criticized, both for its methodology and analysis of the
      results, but it gave a new impulse to the research in this area, stimulating more
      studies on induced cerebral plasticity.

PMID- 26288903
TI  - A Potential Role of Auditory Induced Modulations in Primary Visual Cortex.
AB  - A biologically relevant event is normally the source of multiple, typically
      correlated, sensory inputs. To optimize perception of the outer world, our brain
      combines the independent sensory measurements into a coherent estimate. However,
      if sensory information is not readily available for every pertinent sense, the
      brain tries to acquire additional information via covert/overt orienting
      behaviors or uses internal knowledge to modulate sensory sensitivity based on
      prior expectations. Cross-modal functional modulation of low-level auditory areas
      due to visual input has been often described; however, less is known about
      auditory modulations of primary visual cortex. Here, based on some recent
      evidence, we propose that an unexpected auditory signal could trigger a reflexive
      overt orienting response towards its source and concomitantly increase the
      primary visual cortex sensitivity at the locations where the object is expected
      to enter the visual field. To this end, we propose that three major functionally
      specific pathways are employed in parallel. A stream orchestrated by the superior
      colliculus is responsible for the overt orienting behavior, while direct and
      indirect (via higher-level areas) projections from A1 to V1 respectively enhance
      spatiotemporal sensitivity and facilitate object detectability.

PMID- 26288904
TI  - Visuotactile Temporal Recalibration Transfers Across Different Locations.
AB  - Following prolonged exposure to audiovisual asynchrony, an observer's point of
      subjective simultaneity (PSS) shifts in the direction of the leading modality. It
      has been debated whether other sensory pairings, such as vision and touch, lead
      to a similar temporal recalibration, and if so, whether the internal timing
      mechanism underlying lag visuotactile adaptation is centralised or distributed.
      To address these questions, we adapted observers to vision- and tactile-leading
      visuotactile asynchrony on either their left or right hand side in different
      blocks. In one test condition, participants performed a simultaneity judgment on
      the adapted side (unilateral) and in another they performed a simultaneity
      judgment on the non-adapted side (contralateral). In a third condition,
      participants adapted concurrently to equal and opposite asynchronies on each side
      and were tested randomly on either hand (bilateral opposed). Results from the
      first two conditions show that observers recalibrate to visuotactile
      asynchronies, and that the recalibration transfers to the non-adapted side. These
      findings suggest a centralised recalibration mechanism not linked to the adapted
      side and predict no recalibration for the bilateral opposed condition, assuming
      the adapted effects were equal on each side. This was confirmed in the group of
      participants that adapted to vision- and tactile-leading asynchrony on the right
      and left hand side, respectively. However, the other group (vision-leading on the
      left and tactile-leading on the right) did show a recalibration effect,
      suggesting a distributed mechanism. We discuss these findings in terms of a
      hybrid model that assumes the co-existence of a centralised and distributed
      timing mechanism.

PMID- 26288905
TI  - Vision and Haptics Share Spatial Attentional Resources and Visuotactile
      Integration Is Not Affected by High Attentional Load.
AB  - Human information processing is limited by attentional resources. Two questions
      that are discussed in multisensory research are (1) whether there are separate
      spatial attentional resources for each sensory modality and (2) whether
      multisensory integration is influenced by attentional load. We investigated these
      questions using a dual task paradigm: Participants performed two spatial tasks (a
      multiple object tracking ['MOT'] task and a localization ['LOC'] task) either
      separately (single task condition) or simultaneously (dual task condition). In
      the MOT task, participants visually tracked a small subset of several randomly
      moving objects. In the LOC task, participants either received visual, tactile, or
      redundant visual and tactile location cues. In the dual task condition, we found
      a substantial decrease in participants' performance and an increase in
      participants' mental effort (indicated by an increase in pupil size) relative to
      the single task condition. Importantly, participants performed equally well in
      the dual task condition regardless of whether they received visual, tactile, or
      redundant multisensory (visual and tactile) location cues in the LOC task. This
      result suggests that having spatial information coming from different modalities
      does not facilitate performance, thereby indicating shared spatial attentional
      resources for the tactile and visual modality. Also, we found that participants
      integrated redundant multisensory information optimally even when they
      experienced additional attentional load in the dual task condition. Overall,
      findings suggest that (1) spatial attentional resources for the tactile and
      visual modality overlap and that (2) the integration of spatial cues from these
      two modalities occurs at an early pre-attentive processing stage.

PMID- 26288906
TI  - THE EFFECT OF A CULTURALLY TAILORED SUBSTANCE ABUSE PREVENTION INTERVENTION WITH
      PLAINS INDIAN ADOLESCENTS.
AB  - PURPOSE: To examine the effects of incorporating tribal specific cultural beliefs
      into a tailored substance abuse prevention intervention for at risk rural
      Oklahoma Native American Indian (NAI) Plains adolescents. RESEARCH DESIGN: The 10
      hour Native American Talking Circle Intervention, a school-based, group substance
      abuse prevention program, was implemented over a 8.5 week period and evaluated
      using a one group, pretest-posttest design. Measurements were from the Native
      Self-Reliance Questionnaire and the Substance Problems Scale from Global
      Appraisal of Individual Needs-Quick (GAIN-Q). FINDINGS: One-tailed, paired sample
      t-tests demonstrated significant increase in self-reliance, from 86.227 to 92.204
      (t (43) = -2.580, p = .007) and a decrease in substance abuse/use, from 2.265 to
      1.265 (t (33) = 1.844, p = .007). CONCLUSIONS: The Native Talking Circle
      Intervention based on tribal-specific values and beliefs was shown to be
      effective with substance abuse/use at-risk NAI Plains tribal adolescents.

PMID- 26288907
TI  - POST TRAUMATIC STRESS DISORDER (PTSD) IN ARAB AMERICAN REFUGEE AND RECENT
      IMMIGRANT WOMEN.
AB  - Routine male circumcision (RMC) has been found effective in preventing HIV
      infection in Africa; at the same time, incidence of HIV infection has been rising
      in China. Hence, RMC may be a possible means by which Chinese nationals could
      address increasing HIV infection rates. A focus group study was conducted to
      explore perceptions of RMC among mainland Chinese nationals. The results
      indicated that 1) 90% of participants considered RMC to be an unfamiliar and
      culturally sensitive topic; 2) 80% felt that being uncircumcised had not created
      significant health drawbacks for them or males they knew; and 3) the group
      believed that RMC would not be a good strategy to address rising HIV rates and
      were dubious about the idea of mandated RMC in China. For Chinese nationals,
      cultural traditions regarding RMC appear to outweigh concerns about HIV
      infection.

PMID- 26288908
TI  - ACCULTURATION AS A PREDICTOR OF HEALTH PROMOTING AND LIFESTYLE PRACTICES OF ARAB
      AMERICANS: A DESCRIPTIVE STUDY.
AB  - A cross-sectional descriptive study was done using the Acculturation Rating scale
      of Arab Americans-II, and the Health Promotion and Lifestyle Profile II to assess
      the relationship between acculturation and health promotion practices among Arab
      Americans. Findings showed that attraction to American culture was the most
      important predictor of physical activity; whereas attraction to Arabic culture
      was the most important predictor of stress management and nutritional practices.
      Results suggest that, when demographics are controlled, acculturation predicts
      various health promotion practices in different patterns among members of this
      group. These findings contribute to a better understanding of acculturation's
      influence on immigrants' health promotion practices.

PMID- 26288909
TI  - A GROUNDED THEORY STUDY OF THE PROCESS USED TO NEGOTIATE CONDOM USE AMONG AFRICAN
      AMERICAN WOMEN: REVIEW OF THE LITERATURE.
AB  - This review of the literature identifies themes, variable, goals, and gaps in the
      literature related to HIV and AIDS among African American women. Black Feminist
      Epistemology and symbolic interactionism are used as a theoretical perspective
      and philosophical framework to examine experiences and social behaviors of
      African-American women and to guide and framework to explain the findings from
      the literature. This theoretical perspective/philosophical framework can also be
      used in understanding processes used by African-American women in behavioral,
      social, and intimate interactions.

PMID- 26288911
TI  - Fulfilling the Promise Made 50 Years Ago.

PMID- 26288912
TI  - We Only Have One Opportunity to Make a First Impression.

PMID- 26288910
TI  - MIGRATORY IMPLICATIONS FOR CORONARY HEART DISEASE RISK PREVENTION IN ASIAN
      INDIANS: EVIDENCE FROM THE LEADING HEALTH INDICATORS.
AB  - OBJECTIVEctives of this descriptive comparative study were to (1) review data
      obtained from the World Health Organisation Statistical Information System
      (WHOSIS) database relating to the prevalence of risk factors for coronary heart
      disease (CHD) among Indians and Australians and (2) compare these data with
      published epidemiological studies of CHD riskfactors in adult migrant Asian
      Indians to provide a comprehensive and comparable assessment of risk factors
      relating to CHD and the mortality attributable to these risk factors. Design:
      ThDESIGNdy was undertaken using a database search and integrative review
      methodology. Data were obtained for comparison of CHD risk factors between
      Indians and Australians using the WHOSIS database. For the integrative review the
      MEDLINE, CINAHL, EMBASE, and Cochrane databases were searched using the keywords
      'Migrants', 'Asian Indian', 'India', 'Migration', 'Immigration', 'Risk factors',
      and coronary heart disease. Two reviewers independently assessed the eligibility
      of the studies for inclusion in the review, the methodological quality and
      extracted details of eligible studies. Results from the integrative review on CHD
      risk factors in Asian Indians are presented in a narrative format, along with
      results from the WHOSIS database. Results: TRESULTSadjusted mortality for CHD was
      four times higher in migrant Asian Indians when compared to both the native
      population of the host country and migrants from other countries. Similarly when
      compared to migrants from other countries migrant Asian Indians had the highest
      prevalence of overweight individuals. Prevalence rates for hypercholesterolemia
      were up to 18.5 % among mgrant Asian Indians and migrant Asian Indian women had a
      higher prevalence of hypertriglyceridaemia compared to Caucasian females. Migrant
      Asian Indians also had a higher incidence of hypertension and upto 71 % of migrnt
      Asian Indian men did not meet current guidelines for participation in physical
      activity. Ethnic-specific prevalence of diabetes ranged from 6-7% among the
      normal weight to 19-33% among the obese migrant Asian Indians compared with non
      Hispanic whites. ConclusionCONCLUSIONAsian Indians have an increased risk of CHD.
      Culturally sensitive strategies that recognise the effects of migration and
      extend beyond the health sector should be developed to target lifestyle changes
      in this high risk population.

PMID- 26288913
TI  - Culturally Competent Nursing Care and Promoting Diversity in Our Nursing
      Workforce.

PMID- 26288914
TI  - Nurses Picket Outside Alpena Regional Medical Center. Hospital puts profits above
      the safety of community members.

PMID- 26288915
TI  - Functional and morphological development of the womb throughout life.
AB  - The uterus undergoes changes throughout a woman's life, beginning with her own
      embryonic development when she is still in the womb, commencing a monthly cycle
      at the onset of adulthood, and undergoing dramatic changes during pregnancy and
      parturition. The impact of preterm labour and other perinatal health problems is
      significant, both in human and financial terms; therefore the study of the
      physiological and regulatory changes which the uterus undergoes can be of
      enormous potential benefit. Here we briefly review the current state of
      knowledge, with an emphasis on the importance of changes in connectivity in the
      uterine smooth muscle cell network and on recent mathematical modelling work
      aimed at elucidating the role of spatial heterogeneity in this connected network.

PMID- 26288916
TI  - Healthy, wealthy and wise: the benefits of chemical research.
AB  - Chemistry is the great enabling subject that is central to progress in solving
      global problems. In today's world, these problems are as vital, as new energy
      sources, food, clean water and healthcare. David Philips presents some current
      research in these areas as well as his own work in the field of targeted
      photodynamic therapy of cancer.

PMID- 26288917
TI  - Cyanobacteria and microalgae: a renewable source of bioactive compounds and other
      chemicals.
AB  - Microalgae and cyanobacteria are rich sources of many valuable compounds,
      including important bioactive and biotechnologically relevant chemicals. Their
      enormous biodiversity, and the consequent variability in the respective
      biochemical composition, make microalgae cultivations a promising resource for
      many novel chemically and biologically active molecules and compounds of high
      commercial value such as lipids and dyes. The nature of the chemicals produced
      can be manipulated by changing the cultivation media and conditions. Algae are
      extremely versatile because they can be adapted to a variety of cell culture
      conditions. They do not require arable land, can be cultivated on saline water
      and wastewaters, and require much less water than plants. They possess an
      extremely high growth rate making these microorganisms very attractive for use in
      biofuel production--some species of algae can achieve around 100 times more oil
      than oil seeds. In addition, microalgae and cyanobacteria can accumulate various
      biotoxins and can contribute to mitigate greenhouse gases since they produce
      biomass through carbon dioxide fixation. In this review, we provide an overview
      of the application of microalgae in the production of bioactive and other
      chemicals.

PMID- 26288918
TI  - Biochar composts and composites.
AB  - Research has shown that the carbon content of wastes decreases during composting
      with an increase in the nitrogen content. This indicates that the increased
      microbial activity in the process results in an increased mineralisation rate of
      organic nitrogen. A formula containing biochar in the form of terra preta,
      biochar bokashi, biochar glomalin, biochar hydrogel and biochar mokusaku-eki
      could further enhance the stability of the system and its effectiveness as a soil
      ameliorant. It could increase the cation exchange capacity, reuse crop residue,
      reduce runoff, reduce watering, reduce the quantity of fertiliser increase crop
      yield, build and multiply soil biodiversity, strengthen and rebuild our soil food
      web, sequester atmospheric carbon in a carbon negative process, increase soil pH,
      restructure poor soils, and reduce carbon dioxide/methane/ nitrous oxide/ammonia
      emissions from gardens and fields. This paper considers these claims and also the
      wider environmental implications of the adoption of these processes. The
      intention of this overview is not just to summarise current knowledge of the
      subject, but also to identify gaps in knowledge that require further research.

PMID- 26288920
TI  - Cafe Sci East Africa: talking with young people about science and technology.

PMID- 26288919
TI  - Current strategies for the elucidation of the structures of natural products.
AB  - The application of the results from various physical methods to the isolation,
      characterisation and elucidation of the structures and stereochemistry of natural
      products is reviewed.

PMID- 26288921
TI  - The Diamond Light Source.

PMID- 26288923
TI  - ["What do physicians really read?" Medical journals and pharma-marketing between
      1900 and the late 1970s].
AB  - Scientific Journals are widely used sources in the history science. First and
      foremost they are analyzed under the aspect of professionalization and the
      development of scientific topics. However, the impact of the increasing number of
      advertisements on the journals has been almost systematically excluded from
      historical analysis. The paper analyses the relations between pharma marketing
      and medical journals. However, the emphasis here is not so much on the
      development of print advertisements. Instead the paper uses sources, which were
      produced in the process of marketing to access the history of the medical
      scientific journal, its change and its reception by physicians.

PMID- 26288924
TI  - [Anatomical Vitamin C-Research during National Socialism and the Post-war Period:
      Max Clara's Human Experiments at the Munich Anatomical Institute].
AB  - In autumn of 1942, Max Clara (1899-1966) became chairman of the anatomical
      institute Munich. There, he intensified his research concerning the proof of
      vitamin C with the bodies of executed prisoners which were delivered by the
      Munich-Stadelheim prison. This research on human organs was pursued by applying
      ascorbic acid (Cebion) to prisoners before their execution. The paper
      investigates this intensified and radicalized anatomical research through human
      experiments, which Max Clara conducted in Munich and published from Istanbul
      during the postwar years, as well as its scientific references from the Nazi
      period.

PMID- 26288925
TI  - Enteric diseases remain a major contributor to poor health outcomes in Papua New
      Guinea.

PMID- 26288926
TI  - More resources need to be committed to the provision of safe water sources and
      sanitation in Papua New Guinea.

PMID- 26288927
TI  - Isolation of Vibrio cholerae and other enteric microbiota from patients with
      suspected cholera during the 2009 outbreak in Madang Province, Papua New Guinea.
AB  - When cholera was first detected in Papua New Guinea (PNG) in mid-2009, national
      diagnostic capacity faced many challenges. This was in part due to the non
      endemic status of the outbreak, resulting in few local staff experienced in
      Vibrio cholerae detection and poor access to the required consumables. The PNG
      Institute of Medical Research conducted culture on specimens from suspected
      cholera patients in Madang Province, with presumptive V. cholerae isolates sent
      to Goroka for confirmation. Of 98 samples analysed 15 were culture positive, with
      V. cholerae detected by polymerase chain reaction (PCR) in an additional 3
      samples. Further analyses were conducted to identify other pathogenic bacteria
      from thiosulphate citrate bile salt sucrose (TCBS) agar. Molecular-based assays
      detected enteropathogenic (n = 1) and enterotoxigenic (n = 1) strains of
      Escherichia coli. No other major enteric pathogens were detected. The low
      detection rate of V. cholerae at the provincial level reflects challenges in the
      laboratory diagnosis of cholera and in-country challenges in responding to an
      outbreak of a non-endemic disease, such as lack of in-country diagnostic
      expertise and available consumables in the early stages. It also suggests that
      full aetiological investigations are warranted in future outbreaks of acute
      watery diarrhoea in PNG to fully elucidate the potentially complex aetiology,
      which could in turn guide diagnostic, treatment and prevention measures.

PMID- 26288928
TI  - A short report on the acute diarrhoea outbreak that affected the Ambunti District
      of East Sepik Province in 2010.
AB  - In December 2010 there was a diarrhoea outbreak in Ambunti District, East Sepik
      Province that was presumed to be cholera. This short report describes the
      outbreak and outlines the preventive strategies that were implemented to contain
      the outbreak. Lessons learnt are also discussed.

PMID- 26288929
TI  - Intestinal parasitic infections and anaemia among pregnant women in the highlands
      of Papua New Guinea.
AB  - This study determined the prevalence of intestinal parasitic infections and
      associations with risk factors among pregnant women in their second or third
      trimester in Goroka, Eastern Highlands Province, Papua New Guinea. Among the 201
      pregnant women enrolled in this study, 163 (81%) were infected with one or more
      intestinal parasites. Infections with protozoan parasites (65%) were more
      prevalent than infections with nematodes (31%); protozoan infections included
      Entamoeba histolytica (43%), Giardia lamblia (39%) and Pentatrichomonas hominis
      (14%), and nematode infections included hookworm (18%), Ascaris lumbricoides
      (14%), Strongyloides stercoralis (3%) and Trichuris trichiura (2%). Factors
      associated with higher risk of intestinal parasitic infections in pregnancy
      included being a primigravida for protozoan-only infections and education limited
      to primary school for nematode infections. Altitude-adjusted haemoglobin levels
      were assessed at the beginning of labour for 110 women, with 69 (63%) found to be
      anaemic (haemoglobin < 11 g/dl). There were no associations found between being
      infected in pregnancy and anaemia.

PMID- 26288930
TI  - Evaluation of a WASH intervention demonstrates the potential for improved hygiene
      practices in Hiri District, Central Province.
AB  - Water, sanitation and hygiene (WASH) interventions aim to improve health outcomes
      through provision of safe water supplies and improved sanitation facilities,
      while also promoting better hygiene practices in communities. Population Services
      International introduced a WASH intervention project in the Hiri District,
      Central Province in May 2012. Shortly after its introduction we conducted a
      survey to determine the uptake of the intervention and gauge its impact. We
      invited 400 households to participate in the study, which consisted of a
      questionnaire for the head of the household. A total of 395 questionnaires were
      completed: 314 from households that had participated in the WASH intervention and
      81 that had not (controls). Results demonstrated that improved water sources were
      not routinely used, with a high dependence on well and surface water. While self
      reported handwashing was common, use of soap was not common. Treatment of water
      inside the house was common in the intervention group (95%), compared to 49% in
      the non-WASH group. The study indicates that people in the Hiri District are
      supportive of a WASH intervention, with good uptake of some aspects of the
      intervention. The sustainability of the intervention remains unknown. Targetted
      interventions focusing on community priorities might be beneficial in the future.

PMID- 26288931
TI  - Pigbel in the 21st century: still here, and still in need of an effective
      surveillance system.
AB  - Pigbel remains a likely significant cause of morbidity and mortality in the
      highlands of Papua New Guinea (PNG), two decades after the administration of
      pigbel vaccination ceased. There is a need for an effective surveillance program
      for pigbel to better understand the disease burden and to target communities for
      preventive strategies. This paper reviews the epidemiology, pathogenesis, recent
      history and current data on the burden of pigbel in PNG. We propose a
      surveillance program based on clinical recognition of likely cases and laboratory
      confirmation using an ELISA assay for Clostridium perfringens type C beta-toxin.
      Research aimed at validating this approach in the clinical setting is outlined.

PMID- 26288932
TI  - Evaluation of a rapid immunochromatographic assay for the detection of rotavirus,
      norovirus and adenovirus from children hospitalized with acute watery diarrhea.
AB  - We evaluated the IP-Triple I immunochromatographic rapid test for the detection
      of rotavirus, norovirus and adenovirus using stool samples from children with
      diarrhoea. The detection of norovirus and adenovirus was poor compared to
      polymerase chain reaction assays. However, high sensitivity (92%) and specificity
      (99%) were obtained for the detection of rotavirus.

PMID- 26288933
TI  - A review of diarrhoea aetiology in Papua New Guinea, 1995-2012.
AB  - The large contribution of diarrhoea to morbidity and mortality rates in Papua New
      Guinea (PNG) warrants a significant response to diagnosing aetiology, determining
      appropriate management and reducing risk factors that facilitate transmission of
      enteric pathogens. We conducted a review of literature to assess the extent of
      research published on the aetiology of diarrhoea in PNG between 1995 and 2012. Of
      54 peer-reviewed articles that were selected for review, 25 pertained to
      aetiology. While the majority of articles described typhoid fever and non-typhoid
      salmonellosis, shigellosis, rotavirus, pigbel and cholera were also represented
      in the literature reviewed.

PMID- 26288934
TI  - Clinical management of diarrhoea in children.
AB  - Diarrhoea is one of the commonest reasons children require health care in Papua
      New Guinea (PNG). Acute watery diarrhoea is the commonest form, and is due to
      viruses. Oral rehydration solution, zinc and continued breastfeeding are highly
      effective treatments that can be delivered in homes and health facilities.
      Antibiotics are not useful in acute watery diarrhoea--they make it worse. Deaths
      from acute watery diarrhoea should be rare if basic curative services are
      available. Persistent diarrhoea (lasting longer than 14 days) is commonly
      associated with other co-morbidities, including malnutrition, anaemia, HIV (human
      immunodeficiency virus) infection, parasite (such as Giardia) or worm infections
      and environmental enteropathy. Educating parents on handwashing, food
      preparation, water purification, improvements in sanitation and the home
      environment, breastfeeding, nutrition and immunization are essential in
      preventing diarrhoea. Cholera appeared in PNG in 2009, causing over 500 deaths in
      all age groups. Cholera emerged because of limited access to safe, clean drinking
      water and poor sanitation. Addressing these will have beneficial effects not only
      on cholera but also on all causes of diarrhoea and many other common childhood
      infections.

PMID- 26288935
TI  - Cholera in Papua New Guinea: observations to date and future considerations.
AB  - Cholera is a severe diarrhoeal illness caused by infection with the bacterium
      Vibrio cholerae. From July 2009 to late 2011 Papua New Guinea (PNG) experienced
      thefirst outbreak of cholera ever reported in this country. During this time >
      15,000 cases of cholera were reported, resulting in approximately 500 deaths. The
      origin of this outbreak is unknown, but considering the remote location of the
      initial outbreak an infected international traveller is unlikely to be the
      source. In this paper we review the characteristics of the PNG cholera outbreak
      and discuss the ongoing threat of cholera to the country and the region.

PMID- 26288936
TI  - Sago haemolytic disease: towards understanding a novel food-borne toxicosis.
AB  - Sago haemolytic disease is a rare but sometimes fatal disease found primarily in
      the coastal regions of Papua New Guinea and among groups in which sago is a
      primary source of carbohydrate. It has been known since 1961 and fungi
      consistently have been suspected of being involved. Investigations carried out on
      stored sago and samples recovered from poisoning episodes have failed to indicate
      the consistent presence of mycotoxins. However, fungi (especially Aspergillus,
      Fusarium, Penicillium, Trichoderma) with strong haemolytic activity have been
      associated with sago, particularly when stored in open-weave baskets and sago
      leaf-wrapped bundles. The haemolytic activity has been attributed to fatty acids
      (principally oleic, palmitic, linoleic) contained primarily in the fungal hyphae.
      It is hypothesized that when these acids are released through hyphal breakdown
      during digestion and are present in individuals with a low serum albumin level,
      free fatty acid excess occurs resulting in red cell membrane destruction and
      intravascular haemolysis. In extreme cases, blood transfusion is required.
      Methods of storage providing high levels of access to oxygen favour the
      development of fungi: eg, leaf-encased bundles and open-weave storage favour
      growth over that seen in starch stored under water, such as in earthen vessels.
      Ensuring storage does not exceed 3-4 weeks, encouraging anaerobic conditions of
      the starch and maintaining protein nutrition in communities where sago is relied
      upon should alleviate outbreak episodes.

PMID- 26288937
TI  - GEORGE ARMITAGE MILLER. 3 FEBRUARY 1920 - JULY 2012.

PMID- 26288938
TI  - DAVID RIESMAN. 22 SEPTEMBER 1909 - MAY 2002.

PMID- 26288939
TI  - HENRY TAUBE. 30 NOVEMBER 1915 - NOVEMBER 2005.

PMID- 26288941
TI  - Approaches to Quality Risk Management When Using Single-Use Systems in the
      Manufacture of Biologics.
AB  - Biologics manufacturing technology has made great progress in the last decade.
      One of the most promising new technologies is the single-use system, which has
      improved the efficiency of biologics manufacturing processes. To ensure safety of
      biologics when employing such single-use systems in the manufacturing process,
      various issues need to be considered including possible extractables/leachables
      and particles arising from the components used in single-use systems. Japanese
      pharmaceutical manufacturers, together with single-use suppliers, members of the
      academia and regulatory authorities have discussed the risks of using single-use
      systems and established control strategies for the quality assurance of
      biologics. In this study, we describe approaches for quality risk management when
      employing single-use systems in the manufacturing of biologics. We consider the
      potential impact of impurities related to single-use components on drug safety
      and the potential impact of the single-use system on other critical quality
      attributes as well as the stable supply of biologics. We also suggest a risk
      mitigating strategy combining multiple control methods which includes the
      selection of appropriate single-use components, their inspections upon receipt
      and before releasing for use and qualification of single-use systems.
      Communication between suppliers of single-use systems and the users, as well as
      change controls in the facilities both of suppliers and users, are also important
      in risk-mitigating strategies. Implementing these control strategies can mitigate
      the risks attributed to the use of single-use systems. This study will be useful
      in promoting the development of biologics as well as in ensuring their safety,
      quality and stable supply.

PMID- 26288942
TI  - Taste Masking of Griseofulvin and Caffeine Anhydrous Using Kleptose Linecaps DE17
      by Hot Melt Extrusion.
AB  - The objective of this project was to investigate the potential of Kleptose
      Linecaps DE17 (KLD) in masking the unpleasant/bitter taste of therapeutic agents
      by hot melt extrusion (HME). Griseofulvin (GRI) and caffeine anhydrous (CA) were
      used as a bitter active pharmaceutical ingredient (API) model drugs.
      Thermogravimetric studies confirmed the stability of GRI, CA, and KLD at the
      employed extrusion temperatures. The differential scanning calorimetry (DSC)
      studies revealed a characteristic melting endotherm of GRI at 218-220 degrees C
      and CA at 230-232 degrees C in the physical mixtures as well as in all extrudates
      over the period of study, indicating the crystalline nature of drug. HME of KLD
      was achieved only in the presence of plasticizer. Among the several plasticizers
      investigated, xylitol showed improved processability of KLD at 15% w/w
      concentration. Dissolution studies of HME extrudates using simulated salivary
      medium exhibited ~threefold less release compared to physical mixture at the end
      of 5 min (the lesser drug release, better the taste masking efficiency).
      Furthermore, the results from the sensory evaluation of products in human panel
      demonstrated strong bitter taste in the case of physical mixture compared to the
      HME formulation, suggesting the potential of Kleptose Linecaps DE17 as taste
      masking polymer in melt extruded form. 

PMID- 26288940
TI  - Allergic Inflammation in Aspergillus fumigatus-Induced Fungal Asthma.
AB  - Although fungi are pervasive in many environments, few cause disease in humans.
      Of these, Aspergillus fumigatus is particularly well suited to be a pathogen of
      the human lung. Its physical and biological characteristics combine to provide an
      organism that can cause tremendous morbidity and high mortality if left
      unchecked. Luckily, that is rarely the case. However, repeated exposure to
      inhaled A. fumigatus spores often results in an immune response that carries
      significant immunopathology, exacerbating asthma and changing the structure of
      the lung with chronic impacts to pulmonary function. This review focuses on the
      current understanding of the mechanisms that are associated with fungal exposure,
      sensitization, and infection in asthmatics, as well as the function of various
      inflammatory cells associated with severe asthma with fungal sensitization. 

PMID- 26288943
TI  - In Vivo Evaluation of Transdermal Iodide Microemulsion for Treating Iodine
      Deficiency Using Sprague Dawley Rats.
AB  - The objective of this study was to evaluate the transdermal efficiency of iodide
      microemulsion in treating iodine deficiency using rats as an animal model.
      Animals were fed either iodine-deficient diet (20 MUg/kg iodide) or control diet
      (200 MUg/kg iodide) over a 17-month period. At month 14, iodide microemulsion was
      applied topically in iodine-deficient group and physiological evaluations of
      thyroid gland functions were characterized by monitoring the thyroid hormones
      (T3, T4), thyroid-stimulating hormone (TSH), iodide ion excretion in urine, and
      the overall rat body weights in both groups. Moreover, morphological evaluations
      of thyroid gland before and after treatment were performed by ultrasound imaging
      and through histological assessment. Prior to microemulsion treatment, the levels
      of T3, T4, and TSH in iodine-deficient group were statistically significant as
      compared to that in the control group. The levels of T3 and T4 increased while
      TSH level decreased significantly in iodine-deficient group within the first 4
      weeks of treatment. After treatment, iodide concentration in urine increased
      significantly. There was no statistical difference in weight between the two
      groups. Ultrasound imaging and histological evaluations showed evidence of
      hyperplasia in iodine-deficient group. Topical iodide microemulsion has shown a
      promising potential as a novel delivery system to treat iodine deficiency. 

PMID- 26288949
TI  - Platelets, inflammation and anti-inflammatory drugs in ACS and CAD.

PMID- 26288950
TI  - Anaerobic removal of 1-methoxy-2-propanol under ambient temperature in an EGSB
      reactor.
AB  - Two laboratory-scale expanded granular sludge bed (EGSB) reactors were operated
      at 18 and 25  degrees C, respectively, for the treatment of synthetic wastewater
      composed of ethanol and 1-methoxy-2-propanol (M2P) in a mass ratio of 4:1.
      Reactors were operated first with continuous wastewater supply and after with
      discontinuous substrate supply (5 days a week, 16 h a day) to simulate shift
      working conditions. Under continuous wastewater supply chemical oxygen demand
      (COD), removal efficiency higher than 95 % was achieved at the end of the trial
      applying organic loading rates (OLR) of 29 and 43 kg COD m(-3) day(-1) at 18 and
      25  degrees C; thus, corresponding to M2P OLR of 6.4 and 9.3 kg COD m(-3) day(
      1), respectively. During intermittent supply of substrate, good performance was
      recorded at both temperatures with an OLR of 30 kg COD m(-3) day(-1) (M2P OLR of
      6.6 kg COD m(-3) day(-1)). After 56 h without substrate supply, a decline in
      methane yield of 15-30 % was observed due to the deactivation of the biomass.
      Specific methanogenic activity (SMA) assays were carried out at the end of the
      experiments. SMA values using 1-methoxy-2-propanol as substrate were 24.3 and 7.8
      ml CH4 gVSS(-1) day(-1) at 25  degrees C and at 18  degrees C, respectively. This
      is the first attempt to investigate the removal of 1-methoxy-2-propanol by EGSB
      reactors. 

PMID- 26288951
TI  - Maximizing the production of Scenedesmus obliquus in photobioreactors under
      different irradiation regimes: experiments and modeling.
AB  - Maximizing biomass productivity and photosynthetic efficiency are key factors to
      develop large-scale microalgae cultivation for biodiesel production. If the
      photobioreactor (PBR) is not operated under proper conditions, productivity and
      efficiency values drop considerably. In this work, the growth of Scenedesmus
      obliquus in continuous flat-panel PBR is considered. Experimental data and
      simulations were used with the aim of determining suitable working conditions to
      achieve maximum productivity. Microalgae concentration and productivity have been
      measured in a continuous 250 mL flat-panel PBR as a function of the space-time
      tau. Simulations were performed at both low and high irradiance values, with
      different light regimes (constant light and day-night profiles). Model parameters
      were optimized based on laboratory-scale experimental data, and the importance of
      the maintenance energy requirement as a function of light intensity was outlined.
      The effect of different extent of axial mixing on PBR performances was
      investigated. Results obtained show how to determine optimum working conditions
      and how they could be used in the design of a large-scale PBR to achieve maximum
      microalgal productivity. 

PMID- 26288952
TI  - Metabolic control analysis of L-lactate synthesis pathway in Rhizopus oryzae As
      3.2686.
AB  - The relationship between the metabolic flux and the activities of the pyruvate
      branching enzymes of Rhizopus oryzae As 3.2686 during L-lactate fermentation was
      investigated using the perturbation method of aeration. The control coefficients
      for five enzymes, pyruvate dehydrogenase (PDH), pyruvate carboxylase (PC),
      pyruvate decarboxylase (PDC), lactate dehydrogenase (LDH), and alcohol
      dehydrogenase (ADH), were calculated. Our results indicated significant
      correlations between PDH and PC, PDC and LDH, PDC and ADH, LDH and ADH, and PDC
      and PC. It also appeared that PDH, PC, and LDH strongly controlled the L-lactate
      flux; PDH and ADH strongly controlled the ethanol flux; while PDH and PC strongly
      controlled the acetyl coenzyme A flux and the oxaloacetate flux. Further, the
      flux control coefficient curves indicated that the control of the system
      gradually transferred from PDC to PC during the steady state. Therefore, PC was
      the key rate-limiting enzyme that controls the flux distribution. 

PMID- 26288953
TI  - Evaluation of myocardial infarction size with three-dimensional speckle tracking
      echocardiography: a comparison with single photon emission computed tomography.
AB  - To assess whether global and regional myocardial strains from three-dimensional
      speckle tracking echocardiography (3D-STE) correlate with myocardial infarction
      size (MIS) detected by single photon emission computed tomography (SPECT). Fifty
      seven patients with a history of ST-segment elevation myocardial infarction (MI)
      within 3-6 months were enrolled, alongside 24 healthy volunteers. Left
      ventricular (LV) global area strain, global longitudinal strain (GLS), global
      radial strain, global circumferential strain, left ventricular ejection fraction
      (LVEF) and wall motion score index (WMSI) were measured and compared with the
      corresponding SPECT-detected MISs. Patients were sub-grouped into massive MIS
      group (MIS >= 12%) and small MIS group (MIS < 12%). Myocardial strains of all the
      LV segments were compared with the corresponding MIS. Global myocardial strain
      parameters, LVEF and WMSI of the patients were significantly different from the
      control group (all P < 0.05) and correlated well with MISs, most significantly
      for GLS (r = 0.728, P < 0.01). Significant differences in myocardial strain
      parameters were found between the massive and small MIS groups (all P < 0.05).
      Receiver operating characteristic curve analysis indicated that GLS had a highest
      diagnostic value and when the cutoff was -13.8%, the area under the curve was
      0.84, with the 70.6% sensitivity and 87.5% specificity. Significant differences
      of myocardial strain parameters were observed between segments with and without
      transmural MIs (P < 0.01). 3D-STE myocardial strain parameters evaluated LV
      global MIS, 3D GLS had the highest diagnostic value. It also preliminarily gauged
      the degree of ischemia and necrosis of regional myocardial segments.

PMID- 26288954
TI  - Subtraction coronary computed tomography in patients with severe calcification.
AB  - To investigate the clinical usefulness of subtraction coronary computed
      tomographic angiography (CCTA) in patients with severe calcification. A 320-row
      area detector CT system was used in this study. The subjects were 78 patients (47
      men and 31 women, 739 years of age) with an Agatston score of >300 who were able
      to undergo prospective one-beat scanning during a single breath-hold. The CCTA
      findings were compared against invasive coronary angiography. The diagnostic
      capabilities of CCTA for the severely calcified segments with and without the
      additional information provided by subtraction CCTA were compared. Severe
      calcification was observed in 174 (31.9%) of the 546 segments, and non-assessable
      regions were observed in 74 (13.6%) of the segments. The addition of subtraction
      CCTA information improved the diagnostic accuracy for segments with severe
      calcification from 67.8 to 82.8% on a per-segment basis and from 70.1 to 82.1% on
      a per-patient basis, with non-assessable segments considered to be stenotic. When
      non-assessable segments were considered to be an incorrect diagnosis, the
      diagnostic accuracy was improved from 48.3 to 75.9% on a per-segment basis and
      from 43.3 to 79.1% on a per-patient basis. In addition, when evaluation was
      limited to non-assessable segments, subtraction CCTA provided a diagnostic
      accuracy of 81.1% when non-assessable segments were considered to be stenotic or
      66.2% when non-assessable segments were considered to be an incorrect diagnosis.
      Subtraction CCTA improves the diagnostic capabilities of CCTA in patients with
      severe calcification.

PMID- 26288956
TI  - X-rays and magnetism.
AB  - Magnetism is among the most active and attractive areas in modern solid state
      physics because of intriguing phenomena interesting to fundamental research and a
      manifold of technological applications. State-of-the-art synthesis of advanced
      magnetic materials, e.g. in hybrid structures paves the way to new
      functionalities. To characterize modern magnetic materials and the associated
      magnetic phenomena, polarized x-rays have emerged as unique probes due to their
      specific interaction with magnetic materials. A large variety of spectroscopic
      and microscopic techniques have been developed to quantify in an element, valence
      and site-sensitive way properties of ferro-, ferri-, and antiferromagnetic
      systems, such as spin and orbital moments, and to image nanoscale spin textures
      and their dynamics with sub-ns time and almost 10 nm spatial resolution. The
      enormous intensity of x-rays and their degree of coherence at next generation x
      ray facilities will open the fsec time window to magnetic studies addressing
      fundamental time scales in magnetism with nanometer spatial resolution. This
      review will give an introduction into contemporary topics of nanoscale magnetic
      materials and provide an overview of analytical spectroscopy and microscopy tools
      based on x-ray dichroism effects. Selected examples of current research will
      demonstrate the potential and future directions of these techniques.

PMID- 26288955
TI  - Evaluation of collateral channel classification by computed tomography: the
      feasibility study with reference to invasive coronary angiography.
AB  - To study the feasibility of evaluation of collateral channel (CC) classification
      in patients with coronary chronic total occlusion (CTO) by coronary computed
      tomography angiography (CTA) with reference to invasive coronary angiography
      (ICA) validation. We retrospectively included CTO-confirmed patients who
      underwent both coronary CTA and ICA within 1 month. Collaterals were classified
      by coronary CTA into three types: CC0, no continuous connection between donor and
      recipient vessel; CC1, continuous thread-like connection; CC2, continuous, small
      sidebranch-like connection. With comparison to ICA results, the diagnostic
      performance of CTA-based CC classification was further assessed. 118 patients
      with 132 ICA-confirmed CTO lesions were included. Compared to ICA-based
      evaluation, good overall diagnostic accuracy of CT-based CC classification was
      observed (78%, 103/132, kappa = 0.674, p < 0.001). Coronary CTA was also revealed
      to be accurate in terms of assessment of collateral tortuosity (76.2%, 77/101)
      and identification of principal donor vessel (70.3%, 71/101). Impaired diagnostic
      performance was observed in sub-group of septal collaterals as the accuracy for
      evaluation of the above parameters was 60.6% (20/33), 72.7% (24/33) and 45.5%
      (15/33) respectively. Non-invasive evaluation of CC classification by coronary
      CTA correlates well with ICA findings. In addition, the septal collaterals are
      much less visible at coronary CTA than epicardial collaterals.

PMID- 26288957
TI  - Pretreatment Screening for Hepatitis B Virus Infection in Patients with Systemic
      Lupus Erythematosus.
AB  - Hepatitis B virus (HBV) infection is one of the most common diseases, and
      approximately two billion people are infected with HBV in the world. Until
      recently, hepatitis B surface antigen (HBsAg)-negative patients, carrying
      hepatitis B surface antibody (anti-HBs) and/or hepatitis B core antibody (anti
      HBc), have been considered to have achieved the resolution of HBV infection;
      however, among those patients, the reactivation of HBV has been increasingly
      reported after chemotherapy, hematopoietic stem cell transplantation, or
      immunosuppressive therapy. The reactivation of HBV can cause lethal hepatitis
      called de novo hepatitis B. Therefore, serological examination for HBV infection
      before starting immunosuppressive therapy is now recommended for all patients
      with rheumatic diseases. Systemic lupus erythematosus (SLE) is one of the
      autoimmune diseases characterized by the production of autoantibodies and usually
      requires immunosuppressive therapy. However, to date, a few reports are available
      regarding the prevalence and time course of HBV infection in patients with SLE
      under immunosuppressive therapy. In this review, we update the prevalence and
      time course of HBV infection in lupus patients using our data and previous papers
      available, with a special emphasis on occult HBV infection and a decrease of HBV
      related antibodies (anti-HBs and anti-HBc) under immunosuppressive therapy. This
      review also highlights the screening and management of HBV infection currently
      recommended and the potential role of HBV infection in the pathogenesis of SLE.
      Throughout the present review, we recommend the pretreatment screening for HBV
      infection in patients with SLE as well as patients with other rheumatic diseases.

PMID- 26288958
TI  - Exploiting the phase of NMR signals to carry useful information. Application to
      the measurement of chemical shifts in aliased 2D spectra.
AB  - Taking advantage of the phase of nuclear magnetic resonance (NMR) signals to
      encode NMR information is not easy because of their low precision and their
      sensitivity to nearby signals. We nevertheless demonstrated that the phase in
      indirect dimension of (1) H-(13) C heteronuclear single quantum coherence (HSQC)
      signals could provide carbon chemical shifts at low, but sufficient precision to
      resolve the ambiguities of the chemical shifts in aliased spectra. This approach,
      we called phase-encoding of the aliasing order Na (PHANA), only requires
      inserting a constant delay during the t1 evolution time to obtain spectra where
      signals with mixed phases can be decoded at the processing to reconstruct full
      spectra with a 15-fold increase in resolution.

PMID- 26288959
TI  - A marble in a sack.

PMID- 26288962
TI  - Innovating a way out.

PMID- 26288960
TI  - Evaluation of miR-27a, miR-181a, and miR-570 genetic variants with gallbladder
      cancer susceptibility and treatment outcome in a North Indian population.
AB  - INTRODUCTION: miR-27a, miR-181a, and miR-570 genetic variants have been found to
      play an important role in many cancers, but their contribution in gallbladder
      carcinoma (GBC) has not been explored. Therefore, we investigated the role of
      these micro RNA (miRNA) genetic variants in terms of GBC susceptibility,
      therapeutic response, toxicities associated with chemo-radiotherapy and survival
      outcome. METHODS: This study included 606 GBC patients and 200 healthy controls.
      From among the larger study cohort, 219 patients receiving adjuvant or palliative
      chemo-radiotherapy as per disease status were followed up for toxicity profile.
      Treatment response was recorded in 159 patients who received palliative chemo
      radiotherapy. Genotypes were determined using allelic discrimination assay.
      Statistical analysis was carried out with SPSS version 16. Generalized
      multifactor dimensionality reduction (GMDR) analysis was performed for gene-gene
      interactions. Survival analysis was performed using Kaplan-Meier and Cox
      regression tests. RESULTS: In univariate logistic regression analysis, no
      association with any of the studied polymorphisms was found in overall GBC
      susceptibility. Furthermore, univariate and multivariate analyses revealed no
      significant association with response to chemo-radiotherapy. In GMDR analysis,
      miR-27ars895819, miR-570rs4143815, and miR-181ars12537 combination was found as
      the best gene-gene interaction model for susceptibility and treatment response.
      Furthermore, miR-27ars895819miR-181ars12537 was associated with neutropenia
      toxicity in patients undergoing chemo-radiotherapy. However, miRNA variants had
      no influence over the survival outcomes of GBC patients (locally advanced,
      metastatic). CONCLUSION: In conclusion, the miRNA variants cumulatively influence
      GBC susceptibility and treatment outcomes.

PMID- 26288961
TI  - 3D coral-like nitrogen-sulfur co-doped carbon-sulfur composite for high
      performance lithium-sulfur batteries.
AB  - 3D coral-like, nitrogen and sulfur co-doped mesoporous carbon has been
      synthesized by a facile hydrothermal-nanocasting method to house sulfur for Li-S
      batteries. The primary doped species (pyridinic-N, pyrrolic-N, thiophenic-S and
      sulfonic-S) enable this carbon matrix to suppress the diffusion of polysulfides,
      while the interconnected mesoporous carbon network is favourable for rapid
      transport of both electrons and lithium ions. Based on the synergistic effect of
      N, S co-doping and the mesoporous conductive pathway, the as-fabricated C/S
      cathodes yield excellent cycling stability at a current rate of 4 C (1 C = 1675
      mA g(-1)) with only 0.085% capacity decay per cycle for over 250 cycles and ultra
      high rate capability (693 mAh g(-1) at 10 C rate). These capabilities have rarely
      been reported before for Li-S batteries. 

PMID- 26288963
TI  - The British route to innovation.

PMID- 26288964
TI  - Reworking Greek research.

PMID- 26288970
TI  - Correlated electron systems: Emitting electrons through phonons.

PMID- 26288971
TI  - 2D materials: Ultrafast exciton dynamics.

PMID- 26288972
TI  - Weyl fermions: Massless yet real.

PMID- 26288973
TI  - Material witness: Could polythene clothes be cool?

PMID- 26288974
TI  - Metallic glasses: Cryogenic rejuvenation.

PMID- 26288975
TI  - Colloids at interfaces: Pinned down.

PMID- 26288978
TI  - Neo-adjuvant chemotherapy for advanced stage endometrial carcinoma: a glimmer of
      hope in select patients.
AB  - PURPOSE OF REVIEW: The objective of this review is to conduct a critical
      appraisal of the published literature on the use of neo-adjuvant chemotherapy
      followed by interval debulking in the treatment of stage IVb endometrial
      carcinoma patients. METHODS: Narrative review of the pertinent literature on the
      application of neo-adjuvant chemotherapy and interval surgery in the treatment of
      advanced stage endometrial cancers. RESULTS: Advanced stage endometrial carcinoma
      patients are treated by aggressive cytoreduction followed by adjuvant
      chemotherapy or by chemotherapy alone. The prognosis of patients that cannot
      undergo surgery is extremely poor. Preoperative reduction of tumor burden by
      chemotherapy can facilitate surgery in patients previously considered to have an
      unresectable disease, identify patients with chemo-sensitive tumors that are more
      likely to benefit from surgery, and enable a less aggressive surgery thus
      reducing morbidity. However, only 106 cases of neo-adjuvant chemotherapy were
      documented in the last two decades, majority (76) were described in retrospective
      case reports and case series. The available data may indicate feasibility of neo
      adjuvant treatment in select patients. Compared to patients that had primary
      surgery, neo-adjuvant setting was associated with improved or equivalent survival
      and maximal debulking rates and reduced postoperative morbidity. CONCLUSIONS:
      Until further progress is reached, consideration can be given to recommending neo
      adjuvant chemotherapy followed by interval debulking to patients with poor
      performance status or those patients who the surgeon believes would have
      suboptimal debulking if surgery was attempted.

PMID- 26288976
TI  - New perspectives for Rashba spin-orbit coupling.
AB  - In 1984, Bychkov and Rashba introduced a simple form of spin-orbit coupling to
      explain the peculiarities of electron spin resonance in two-dimensional
      semiconductors. Over the past 30 years, Rashba spin-orbit coupling has inspired a
      vast number of predictions, discoveries and innovative concepts far beyond
      semiconductors. The past decade has been particularly creative, with the
      realizations of manipulating spin orientation by moving electrons in space,
      controlling electron trajectories using spin as a steering wheel, and the
      discovery of new topological classes of materials. This progress has
      reinvigorated the interest of physicists and materials scientists in the
      development of inversion asymmetric structures, ranging from layered graphene
      like materials to cold atoms. This Review discusses relevant recent and ongoing
      realizations of Rashba physics in condensed matter. 

PMID- 26288977
TI  - Clinical characteristics of adnexal torsion in premenarchal patients.
AB  - PURPOSE: To compare clinical characteristics of adnexal torsion in premenarchal
      patients as compared to postmenarchal ones. METHODS: A retrospective 22-year
      cohort of all cases of surgically verified adnexal torsion in premenarchal and
      postmenarchal patients (excluding postmenopausal and pregnant patients). Data
      collected included symptoms, signs and imaging at presentation, surgical mode,
      and procedure and histology. RESULTS: 16 cases of adnexal torsion among
      premenarchal patients were compared to 302 cases among postmenarchal ones.
      Clinical presentation was similar, notable only for more nausea and vomiting
      among the premenarchal group. Ovarian cysts were more commonly demonstrated among
      postmenarchal patients (82.4 and 30.8%, p < 0.001), as opposed to a normal
      adnexal appearance on ultrasound, which was more common in premenarchal patients
      (69.3 vs. 17.2%, p < 0.001). Absent Doppler flow, when preformed, did not differ
      statistically between the groups. Laparoscopic detorsion only was more commonly
      performed in premenarchal patients (56.2 vs. 19.8%, p = 0.001), with a trend for
      detorsion and cystectomy/fenestration, which were more common in postmenarchal
      surgeries (25 vs. 50.6%, p = 0.06). Histology was similar among both groups, with
      no cases of malignancy in premenarchal patients. CONCLUSION: Adnexal torsion in
      premenarchal patients is rare, presents similarly to older patients, but involves
      a normal adnexa in 69% of cases, therefore requiring a high index of suspicion in
      any premenarchal patient with acute onset abdominal pain.

PMID- 26288979
TI  - The effects of progesterone in women undergoing preterm labor.

PMID- 26288980
TI  - Comment to the letter: the effects of progesterone in women undergoing preterm
      labor.

PMID- 26288981
TI  - Comparison of pregnancy rates in pre-treatment male infertility and low total
      motile sperm count at insemination.
AB  - PURPOSE: In intrauterine insemination (IUI), total motile sperm count (TMSC) is
      an important predictor of pregnancy. However, the clinical significance of a poor
      TMSC on the day of IUI in a patient with prior normal semen analysis (SA) is
      unclear. We performed this study to determine if these patients perform as poorly
      as those who had male factor infertility diagnosed prior to commencing treatment.
      METHODS: 147 males with two abnormal SA based on the 2010 World Health
      Organization criteria underwent 356 IUI with controlled ovarian hyper-stimulation
      (COH). Their pregnancy rates were compared to 120 males who had abnormal TMSC at
      the time of 265 IUI with COH, in a retrospective university-based study. RESULTS:
      The two groups were comparable in female age (p = 0.11), duration of infertility
      (p = 0.17), previous pregnancies (p = 0.13), female basal serum FSH level (p =
      0.54) and number of mature follicles on the day of ovulation trigger (p = 0.27).
      Despite better semen parameters on the day of IUI in the pre-treatment male
      factor infertility group (TMSC mean +/- SD: 61 +/- 30 million vs. 3.5 +/- 2
      million, p < 0.001), pregnancy rates were much higher in the group with low TMSC
      on the day of IUI (5 % vs. 17 %, p < 0.001). CONCLUSION: A patient with a recent
      (within 6 months) normal pre-treatment SA but low TMSC on the day of IUI likely
      has a reasonable chance to achieve pregnancy, and does not perform as poorly as
      subjects previously diagnosed with male factor infertility. More studies should
      be performed to confirm these findings.

PMID- 26288982
TI  - Obesity prevention: Moving beyond the food addiction debate.

PMID- 26288983
TI  - Is love possible without Kiss1-es?

PMID- 26288984
TI  - New practical definitions for the diagnosis of autosomal recessive spastic ataxia
      of Charlevoix-Saguenay.
AB  - OBJECTIVE: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is
      caused by mutations in the SACS gene. SACS encodes sacsin, a protein whose
      function remains unknown, despite the description of numerous protein domains and
      the recent focus on its potential role in the regulation of mitochondrial
      physiology. This study aimed to identify new mutations in a large population of
      ataxic patients and to functionally analyze their cellular effects in the
      mitochondrial compartment. METHODS: A total of 321 index patients with spastic
      ataxia selected from the SPATAX network were analyzed by direct sequencing of the
      SACS gene, and 156 patients from the ATAXIC project presenting with congenital
      ataxia were investigated either by targeted or whole exome sequencing. For
      functional analyses, primary cultures of fibroblasts were obtained from 11
      patients carrying either mono- or biallelic variants, including 1 case harboring
      a large deletion encompassing the entire SACS gene. RESULTS: We identified
      biallelic SACS variants in 33 patients from SPATAX, and in 5 nonprogressive
      ataxia patients from ATAXIC. Moreover, a drastic and recurrent alteration of the
      mitochondrial network was observed in 10 of the 11 patients tested.
      INTERPRETATION: Our results permit extension of the clinical and mutational
      spectrum of ARSACS patients. Moreover, we suggest that the observed mitochondrial
      network anomalies could be used as a trait biomarker for the diagnosis of ARSACS
      when SACS molecular results are difficult to interpret (ie, missense variants and
      heterozygous truncating variant). Based on our findings, we propose new
      diagnostic definitions for ARSACS using clinical, genetic, and cellular criteria.

PMID- 26288985
TI  - In the Endemic Setting, Clostridium difficile Ribotype 027 Is Virulent But Not
      Hypervirulent.
AB  - BACKGROUND: Conflicting reports have been published on the association between
      Clostridium difficile ribotypes and severe disease outcomes in patients with C.
      difficile infection (CDI); several so-called hypervirulent ribotypes have been
      described. We performed a multicenter study to assess severe disease presentation
      and severe outcomes among CDI patients infected with different ribotypes.
      METHODS: Stool samples that tested positive for C. difficile toxin were collected
      and cultured from patients who presented to any of 7 different hospitals in
      Houston, Texas (2011-2013). C. difficile was characterized using a fluorescent
      PCR ribotyping method. Medical records were reviewed to determine clinical
      characteristics and ribotype association with severe CDI presentation (ie,
      leukocytosis and/or hypoalbuminemia) and severe CDI outcomes (ie, ICU admission,
      ileus, toxic megacolon, colectomy, and/or in-hospital death). RESULTS: Our study
      included 715 patients aged 61+/-18 years (female: 63%; median Charlson
      comorbidity index: 2.5+/-2.4; hospital-onset CDI: 45%; severe CDI: 36.7%; severe
      CDI outcomes: 12.3%). The most common ribotypes were 027, 014-020, FP311, 002,
      078-126, and 001. Ribotype 027 was a significant independent predictor of severe
      disease (adjusted odds ratio [aOR], 2.24; 95% confidence interval [CI], 1.53
      3.29; P<.001) and severe CDI outcomes (aOR, 1.71; 95% CI, 1.02-2.85; P=.041)
      compared with all other ribotypes in aggregate. However, in an analysis using all
      common ribotypes as individual variables, ribotype 027 was not associated with
      severe CDI outcomes more often than other ribotypes. CONCLUSION: Ribotype 027
      showed virulence equal to that of other ribotypes identified in this endemic
      setting. Clinical severity markers of CDI may be more predictive of severe CDI
      outcomes than a particular ribotype.

PMID- 26288986
TI  - Accurate estimate of pancreatic T2* values: how to deal with fat infiltration.
AB  - PURPOSE: We examined different approaches aimed to deal with the signal
      fluctuation of pancreatic T2* values due to fat infiltration in order to obtain
      accurate estimates of iron overload. METHODS: Pancreatic T2* values were assessed
      in 20 patients (13 females, 37.24 +/- 9.12 years) enrolled in the Myocardial Iron
      Overload in Thalassemia network without and with the application of fat
      suppression-FS (T2*-NoFS and T2*-FS). T2* values were assessed in three different
      ways: (1) from the immediate fit (original T2*); (2) discarding the echoes until
      the achievement of a good visual concordance between the signal and the model
      (final_vis T2*); (3) eliminating the echoes until the achievement of a fitting
      error (known) <5% (final_thres T2*). RESULTS: For the T2*-NoFS sequence the
      original T2* values were significantly higher than the final_vis T2* values
      (difference:4.8 +/- 6.1 ms; P < 0.0001) and the final_thres T2* values
      (difference:4.3 +/- 6.1 ms; P = 0.006). For the T2*-FS sequence the original T2*
      values were comparable to final_vis and final_thres T2* values. The original T2*
      FS values were significantly different from the original T2*-NoFS values. The
      final_vis T2*-FS values were comparable to the final_vis T2*-NoFS values and the
      final_thresh T2*-FS values were comparable to the final_thresh T2*-NoFS values.
      For both T2*-FS and T2*-NoFS sequences, the final_thres T2* values were not
      significantly different from the final_vis T2* values and no bias was present.
      CONCLUSIONS: In the clinical practice, an accurate pancreatic iron overload
      assessment should be done by applying FS and, when needed, by discarding the TEs
      until the fitting error goes below 5%.

PMID- 26288987
TI  - Predictive models for lymph node metastases in patients with testicular germ cell
      tumors.
AB  - PURPOSE: To develop predictive models for lymph node (LN) metastasis in
      testicular germ cell tumors. MATERIALS AND METHODS: 291 patients with testicular
      germ cell tumors were included, which were divided into seminomatous and
      nonseminomatous groups. For screening the risk factors for LN metastasis, the
      tumor-related characteristics (including histopathological information and tumor
      markers) alpha fetoprotein and the lymph node-related features on CT were
      compared between metastatic cases and nonmetastatic cases. Two logistic
      regression models were built for each histological group, one depending on all
      tumor- and lymph node-related risk factors (Model 1) and another only on tumor
      related factors (Model 2). Receivers operating characteristic curves were used to
      evaluate the predictive abilities of these models. RESULTS: 117 positive
      nodes/regions were identified in 68 patients, including 51 metastases and 17
      occult metastases. Based on the selected independent risk factors, the
      sensitivity, specificity, accuracy, positive predictive value, and negative
      predictive value of Models 1 and 2 in seminomatous and nonseminomatous groups
      were (95.5%, 95.3%, 95.3%, 77.8%, and 99.2%), (63.6%, 83.6%, 80.7%, 40.0%, and
      93.0%), (93.5%, 94.7%, 94.3%, 89.6%, and 96.8%), and (89.1%, 44.2%, 58.9%, 43.6%,
      and 89.4%), respectively. CONCLUSION: Two predictive models for each seminomatous
      and nonseminomatous testicular tumor were established based on lymph node- and
      tumor-related risk factors. In patients with tumor and lymph node-related risk
      factors, regular CT surveillance is likely sufficient for predicting LN status,
      while in the patients without any tumor and lymph node-related risk factors a
      long interval-time CT follow-up should be considered. Additionally, right side
      tumors tend to involve contralateral LNs compared to left side ones. Positive
      inguinal LNs more frequently occur in patients with a history of groin surgery.

PMID- 26288988
TI  - Proteomics Insights into the Biomass Hydrolysis Potentials of a Hypercellulolytic
      Fungus Penicillium funiculosum.
AB  - The quest for cheaper and better enzymes needed for the efficient hydrolysis of
      lignocellulosic biomass has placed filamentous fungi in the limelight for
      bioprospecting research. In our search for efficient biomass degraders, we
      identified a strain of Penicillium funiculosum whose secretome demonstrates high
      saccharification capabilities. Our probe into the secretome of the fungus through
      qualitative and label-free quantitative mass spectrometry based proteomics
      studies revealed a high abundance of inducible CAZymes and several nonhydrolytic
      accessory proteins. The preferential association of these proteins and the
      attending differential biomass hydrolysis gives an insight into their
      interactions and clues about possible roles of novel hydrolytic and nonhydrolytic
      proteins in the synergistic deconstruction of lignocellulosic biomass. Our study
      thus provides the first comprehensive insight into the repertoire of proteins
      present in a high-performing secretome of a hypercellulolytic Penicillium
      funiculosum, their relative abundance in the secretome, and the interaction
      dynamics of the various protein groups in the secretome. The gleanings from the
      stoichiometry of these interactions hold a prospect as templates in the design of
      cost-effective synthetic cocktails for the optimal hydrolysis of biomass. 

PMID- 26288990
TI  - Indications and techniques for robotic pelvic and para-aortic lymphadenectomy in
      gynecologic oncology.
AB  - Robotic-assisted laparoscopy is now the most common surgical method for treatment
      of early-stage endometrial, cervical, and a growing number of ovarian cancers in
      the U.S. Para-aortic and pelvic lymphadenectomy is integral to surgical staging
      and subsequent treatment planning. This article reviews current staging outcomes
      with robotic surgery for gynecologic cancers, and describes both trans
      peritoneal, extra-peritoneal aortic dissection techniques, and the integration of
      pelvic sentinel lymph node mapping.

PMID- 26288989
TI  - Altering sphingolipid composition with aging induces contractile dysfunction of
      gastric smooth muscle via K(Ca) 1.1 upregulation.
AB  - K(Ca) 1.1 regulates smooth muscle contractility by modulating membrane potential,
      and age-associated changes in K(Ca) 1.1 expression may contribute to the
      development of motility disorders of the gastrointestinal tract. Sphingolipids
      (SLs) are important structural components of cellular membranes whose altered
      composition may affect K(Ca) 1.1 expression. Thus, in this study, we examined
      whether altered SL composition due to aging may affect the contractility of
      gastric smooth muscle (GSM). We studied changes in ceramide synthases (CerS) and
      SL levels in the GSM of mice of varying ages and compared them with those in
      young CerS2-null mice. The levels of C16- and C18-ceramides, sphinganine,
      sphingosine, and sphingosine 1-phosphate were increased, and levels of C22, C24:1
      and C24 ceramides were decreased in the GSM of both aged wild-type and young
      CerS2-null mice. The altered SL composition upregulated K(Ca) 1.1 and increased
      K(Ca) 1.1 currents, while no change was observed in K(Ca) 1.1 channel activity.
      The upregulation of KC a 1.1 impaired intracellular Ca2+mobilization and
      decreased phosphorylated myosin light chain levels, causing GSM contractile
      dysfunction. Additionally, phosphoinositide 3-kinase, protein kinase Czeta , c
      Jun N-terminal kinases, and nuclear factor kappa-B were found to be involved in
      K(Ca) 1.1 upregulation. Our findings suggest that age-associated changes in SL
      composition or CerS2 ablation upregulate K(Ca) 1.1 via the phosphoinositide 3
      kinase/protein kinase Czeta /c-Jun N-terminal kinases/nuclear factor kappa-B
      mediated pathway and impair Ca2+ mobilization, which thereby induces the
      contractile dysfunction of GSM. CerS2-null mice exhibited similar effects to aged
      wild-type mice; therefore, CerS2-null mouse models may be utilized for
      investigating the pathogenesis of aging-associated motility disorders.

PMID- 26288991
TI  - Synthesis of N-dialkylphosphoryl iminosugar derivatives and their
      immunosuppressive activities.
AB  - Twelve novel N-dialkylphosphoryliminosugar derivatives were synthesized and their
      immunosuppressive activities were evaluated on the proliferation of the mouse
      splenocytes and the secretion of IFN-gamma and IL-4. The experimental data
      demonstrated that the iminosugars with the double long alkyl chains exhibited
      better inhibitory effects than those with the single long alkyl chain, and the
      iminosugars with the 10-carbon linear alkyl chain exhibited the strongest
      immunosuppressive activities. The assay of the cytokine secretion showed that the
      introduction of dialkyl chains on iminosugars could regulate the polarization of
      immune inhibition by varying the length of the alkyl chains. The disclosure of
      the structure-activity relationships may benefit the structural modifications of
      iminosugars to find new types of immunosuppressive agents. 

PMID- 26288992
TI  - The structure of wheat bread influences the postprandial metabolic response in
      healthy men.
AB  - Postprandial high glucose and insulin responses after starchy food consumption,
      associated with an increased risk of developing several metabolic diseases, could
      possibly be improved by altering food structure. We investigated the influence of
      a compact food structure; different wheat products with a similar composition
      were created using different processing conditions. The postprandial glucose
      kinetics and metabolic response to bread with a compact structure (flat bread,
      FB) was compared to bread with a porous structure (control bread, CB) in a
      randomized, crossover study with ten healthy male volunteers. Pasta (PA), with a
      very compact structure, was used as the control. The rate of appearance of
      exogenous glucose (RaE), endogenous glucose production, and glucose clearance
      rate (GCR) was calculated using stable isotopes. Furthermore, postprandial plasma
      concentrations of glucose, insulin, several intestinal hormones and bile acids
      were analyzed. The structure of FB was considerably more compact compared to CB,
      as confirmed by microscopy, XRT analysis (porosity) and density measurements.
      Consumption of FB resulted in lower peak glucose, insulin and glucose-dependent
      insulinotropic polypeptide (ns) responses and a slower initial RaE compared to
      CB. These variables were similar to the PA response, except for RaE which
      remained slower over a longer period after PA consumption. Interestingly, the GCR
      after FB was higher than expected based on the insulin response, indicating
      increased insulin sensitivity or insulin-independent glucose disposal. These
      results demonstrate that the structure of wheat bread can influence the
      postprandial metabolic response, with a more compact structure being more
      beneficial for health. Bread-making technology should be further explored to
      create healthier products. 

PMID- 26288993
TI  - Theory of ferrimagnetism in the Hubbard model on bipartite lattices with spectral
      symmetry.
AB  - The Hubbard model is one of the most important models in condensed matter
      physics. In this paper, we developed a theory of ferrimagnetism in the Hubbard
      model on bipartite lattices with spectral symmetry. By taking three models as
      examples, we studied the ferrimagnetic orders that emerge from three typical
      fermionic systems--metal, semi-metal and (Chern) insulator. In particular, we
      found that there may exist various ferrimagnetic orders and explored the
      universal features.

PMID- 26288994
TI  - The impact of food components on the intrinsic dissolution rate of ketoconazole.
AB  - To accurately predict the in vivo performance of drugs from an in vitro
      dissolution test, the dissolution conditions used are supposed to be similar to
      those present in the gastrointestinal milieu. Post-prandial gastric fluid
      contains partially digested food mixtures consisting of fat, protein and
      carbohydrate. Despite this, the compendia dissolution medium recommended to
      simulate the gastric fluid is still composed of a simple solution of hydrochloric
      acid and sodium chloride with or without the addition of pepsin. Therefore, in
      this investigation, biorelevant dissolution media were developed to evaluate the
      impact of food constituents; milk with different fat contents, egg albumin,
      gelatin, casein, gluten, carbohydrates and amino acids on the intrinsic
      dissolution behavior of ketoconazole. Most of the food additives that were
      evaluated enhanced the apparent solubility of the drug but to different extents.
      The greatest enhancement in dissolution was observed in media containing either
      neutral amino acids or media based on milk mixtures. The formation of complexes
      between the drug and the additives most likely accounted for the solubilizing
      effect and in milk-containing media, the effect was attributed to the whole
      complex structure of milk rather than simply its fat content. These results
      highlight the potential effect of the type of ingested meal on drug dissolution
      and subsequent bioavailability. 

PMID- 26288995
TI  - Formulation optimization of a drug in adhesive transdermal analgesic patch.
AB  - CONTEXT: Conventional pain management approaches have limitations such as
      gastrointestinal side effects, frequent dosing, and difficulties in swallowing
      medications. Hence, to overcome these limitations, we developed a transdermal
      analgesic patch. OBJECTIVE: This study was designed to formulate a drug in
      adhesive transdermal patch with codeine (CDB) and acetaminophen (APAP) that may
      potentially treat moderate pain in children. MATERIALS AND METHODS: Three
      analgesic drugs hydrocodone bitartrate, CDB and APAP were screened by a slide
      crystallization study using polarized light microscope and their permeation
      profiles were studied using vertical Franz diffusion cells across porcine ear
      skin, dermatomed human skin and epidermis for 24 h, and the samples were
      quantified by high performance liquid chromatography. Patches used for permeation
      studies were prepared by dissolving sub-saturation concentration of the drug(s)
      in adhesive (with/without 5% w/w oleic acid [OA]), cast with a film casting
      knife. RESULTS AND DISCUSSION: Among the three drugs screened, CDB demonstrated
      the best permeation profile (660.21 ug/cm(2)), and shortest lag time (4.35 +/-
      0.01 h), and hence was chosen for patch studies. The highest concentration of CDB
      in the patch at which drug does not crystallize was determined as 40% of its
      saturation solubility (Cs) and that of APAP was determined as 200% of its Cs. CDB
      standalone patch delivered 105.48 ug/cm(2) of CDB, while the CDB-APAP combination
      patch with 5% w/w OA delivered 151.40 ug/cm(2) CDB and 58.12 ug/cm(2) APAP in 24
      h. CONCLUSION: Drug-in-adhesive patches using CDB and APAP were developed for
      infants and children. Addition of OA enhanced solubility and permeation of drugs.

PMID- 26288996
TI  - Potential interaction between zinc ions and a cyclodextrin-based diclofenac
      formulation.
AB  - Complexes of diclofenac sodium (DF-Na) with hydroxypropyl betacyclodextrin
      (HPbetaCD) were prepared by co-evaporation in a 1:1 ratio and characterized in
      light of previously reported data. Phase solubility diagrams were obtained for DF
      Na with HPbetaCD in the presence and absence of zinc ions. Dissolution profiles
      were obtained for DF-Na and its HPbetaCD complex at acidic (pH 1.2) as well as in
      phosphate buffer (pH 6.8), in the presence and absence of zinc. HPbetaCD, as
      expected, was shown to improve the dissolution of DF-Na in acidic medium but not
      in phosphate buffer (pH 6.8). The presence of zinc ions decreased the in vitro
      dissolution of DF-HPbetaCD complex in acidic medium (pH 1.2) but not in phosphate
      buffer (pH 6.8). It was confirmed that the precipitate that was formed by zinc
      ions in the presence of HPbetaCD and DF-Na contained no cyclodextrin and most
      likely it was a mixture of the complexes: DF2-Zn and DF-Zn with some molecules of
      water. In vivo experiments on rats have shown that HPbetaCD has no statistically
      significant effect on absorption or bioavailability of DF-Na in spite of the
      observed improvement of its in vitro dissolution by HPbetaCD. Moreover, zinc ions
      were shown to decrease the absorption rate of DF-Na in rats model but did neither
      significantly alter the absorption nor bioavailability of DF-HPbetaCD complex.
      The zinc induced precipitates of DF were shown to have significantly different
      crystalline properties when HPbetaCD was present. Therefore, the pharmaceutical
      details of a DF-Na preparation should be considered when designing the
      formulation and predicting possible interaction between DF-Na (or other potential
      NSAIDs) and zinc metal. 

PMID- 26288997
TI  - Characterization and evaluation of metformin-loaded solid lipid nanoparticles for
      celluar and mitochondrial uptake.
AB  - Considered a popular drug for diabetes in recent years, metformin was determined
      to have a moderate anti-tumor effect, particularly in breast cancer. In this
      study, the anticancer mechanism of metformin was verified by preparing solid
      lipid nanoparticles (SLNs) and chitosan-modified solid lipid nanoparticles
      (CSLNs) containing metformin and then estimating the potential of these SLNs for
      uptake in cells and mitochondria. Metformin-SLNs were prepared using an
      emulsification and low-temperature solidification method. The mean particle size,
      zeta potential, entrapment efficiency, and loading efficiency of metformin-SLNs
      and metformin chitosan-modified SLNs were 102.3 +/- 4.16 and 200.1 +/- 17.69 nm, 
      21.25 +/- 4.89 and 50.6 +/- 4.09 mv, 26.25 +/- 2.59% and 33.6 +/- 2.21%, and 1.74
      +/- 0.16% and 1.46 +/- 0.10%, respectively. TEM images showed that both the
      nanoparticles had spherical morphologies with no aggregation. Results of cellular
      and mitochondrial uptake showed that the metformin-SLNs were easier to uptake in
      cells and mitochondria than the pure drug group (that was the control group
      without SLN structure modification). The findings of this research provide a
      basis for conducting further studies on the anticancer mechanism of metformin. 

PMID- 26288998
TI  - P-glycoprotein inhibitors: synthesis and in vitro evaluation of a preactivated
      thiomer.
AB  - The aim of this study was to synthesize the preactivated thiomer poly(acrylic
      acid)-cyteine-2-mercaptonicotinic acid (PAA-Cys-2MNA) and to evaluate its P
      glycoprotein (P-gp) inhibitory properties. The thiomer (PAA-Cys) was synthesized
      by covalent immobilization of thiol groups on poly(acrylic acid) (PAA) with a
      molecular mass of 250 kDa followed by immobilization of 2-mercaptonicotinic acid
      (2MNA) to thiol groups via disulfide bond formation resulting in PAA-Cys-2MNA. P
      gp inhibitory effect of this preactivated thiomer was evaluated on Caco-2 cells.
      Transports of rhodamine 123 at 37  degrees C with and without verapamil and at 4 
      degrees C were performed to evaluate P-gp function of cells. In total, 1571.81 +/
      156.18 umol thiol groups were immobilized per gram of polymer that were in the
      next step by 99.88% preactivated. The enhancement ratios of Papp calculated from
      the ratio between Papp of rhodamine 123 in the presence of P-gp inhibitors and
      Papp of rhodamine 123 alone were 2.36, 2.09, and 1.84-fold in the presence of PAA
      Cys-2MNA, PAA-Cys, and PAA, respectively. Because of its pronounced P-gp
      inhibitory effect, PAA-Cys-2MNA could be considered as promising macromolecular P
      gp inhibitor for various drug delivery systems.

PMID- 26288999
TI  - Risk assessment of supply chain for pharmaceutical excipients with AHP-fuzzy
      comprehensive evaluation.
AB  - As the essential components in formulations, pharmaceutical excipients directly
      affect the safety, efficacy, and stability of drugs. Recently, safety incidents
      of pharmaceutical excipients posing seriously threats to the patients highlight
      the necessity of controlling the potential risks. Hence, it is indispensable for
      the industry to establish an effective risk assessment system of supply chain. In
      this study, an AHP-fuzzy comprehensive evaluation model was developed based on
      the analytic hierarchy process and fuzzy mathematical theory, which
      quantitatively assessed the risks of supply chain. Taking polysorbate 80 as the
      example for model analysis, it was concluded that polysorbate 80 for injection
      use is a high-risk ingredient in the supply chain compared to that for oral use
      to achieve safety application in clinic, thus measures should be taken to control
      and minimize those risks. 

PMID- 26289000
TI  - Preparation of hydrogel embedded polymer-growth factor conjugated nanoparticles
      as a diabetic wound dressing.
AB  - CONTEXT: Growth factors act in an integrated manner to promote the wound-healing
      process. However, probably due to early inactivation of these molecules in the
      wound site, their topical administration scarcely leads to a significant
      improvement in chronic wound repair. OBJECTIVES: With the aim of identifying
      improved therapeutics, a sodium carboxymethyl chitosan-recombinant human
      epidermal growth factor conjugate (NaCMCh-rhEGF) was developed. It is believed
      that conjugation will protect rhEGF against proteolysis and will mediate rhEGF
      release by alpha-amylase. MATERIAL AND METHODS: As hydrogels possess most of the
      desirable characteristics of an ideal dressing, we used our previously described
      chitosan-based hydrogel as a carrier for NaCMCh-rhEGF nanoparticles to make a
      novel wound dressing system. To evaluate the biological activity of NaCMCh-rhEGF
      and free rhEGF, the proliferation of fibroblasts was measured using a
      colorimetric assay. Additionally the stability of conjugated and free rhEGF
      against proteases was estimated. RESULT AND DISCUSSION: In vitro results revealed
      that the conjugated form exhibited more stability against proteolysis and also
      preserved its biological activity. Furthermore, in vivo studies were performed
      using an excision wound model on diabetic rats. After 15 d, the wound area in
      NaCMCh-rhEGF-hydrogel dressing group was significantly smaller than other groups
      and showed histological parameters equal to positive wound control group.
      CONCLUSION: A polymer conjugated rhEGF was developed that was more stable against
      proteases and reserved the biological activity of the drug. This dressing appears
      to be a competent candidate for chronic wound healing.

PMID- 26289001
TI  - Use of the Flory-Huggins theory to predict the solubility of nifedipine and
      sulfamethoxazole in the triblock, graft copolymer Soluplus.
AB  - CONTEXT: Drug dispersed in a polymer can improve bioavailability; dispersed
      amorphous drug undergoes recrystallization. Solid solutions eliminate amorphous
      regions, but require a measure of the solubility. OBJECTIVE: Use the Flory
      Huggins Theory to predict crystalline drugs solubility in the triblock, graft
      copolymer Soluplus(r) to provide a solid solution. MATERIALS AND METHODS:
      Physical mixtures of the two drugs with similar melting points but different
      glass forming ability, sulfamethoxazole and nifedipine, were prepared with
      Soluplus(r) using a quick technique. Drug melting point depression (MPD) was
      measured using differential scanning calorimetry. The Flory-Huggins Theory
      allowed: (1) interaction parameter, chi, calculation using MPD data to provide a
      measure of drug-polymer interaction strength and (2) estimation of the free
      energy of mixing. A phase diagram was constructed with the MPD data and glass
      transition temperature (Tg) curves. RESULTS: The interaction parameters with
      Soluplus(r) and the free energy of mixing were estimated. Drug solubility was
      calculated by the intersection of solubility equations and that of MPD and Tg
      curves in the phase diagram. DISCUSSION: Negative interaction parameters
      indicated strong drug-polymer interactions. The phase diagram and solubility
      equations provided comparable solubility estimates for each drug in Soluplus(r).
      Results using the onset of melting rather than the end of melting support the use
      of the onset of melting. CONCLUSION: The Flory-Huggins Theory indicates that
      Soluplus(r) interacts effectively with each drug, making solid solution formation
      feasible. The predicted solubility of the drugs in Soluplus(r) compared favorably
      across the methods and supports the use of the onset of melting.

PMID- 26289002
TI  - Development of low density azithromycin-loaded polycaprolactone microparticles
      for pulmonary delivery.
AB  - CONTEXT: The development of low-density polymeric microparticles may be a useful
      approach to deliver antibiotics such as azithromycin into the lung. OBJECTIVE:
      The aim of this study was to develop azithromycin-loaded low density
      polycaprolactone microparticles by the double emulsion/solvent evaporation
      method. MATERIALS AND METHODS: Microparticles were prepared and characterized
      according to their physicochemical properties, drug loading, and drug release
      profiles. A full 2(3) factorial design was used to evaluate the effect of some
      independent variables on the drug loading and aerodynamic diameter of the
      particles. An in silico pulmonary deposition model was used to predict the lung
      deposition profiles for the formulations. RESULTS AND DISCUSSION: The resulting
      particles presented drug loading up to 23.1% (wt%) and mean geometric diameters
      varying from 4.0 um to 15.4 um. Bulk and tapped densities were low, resulting in
      good or excellent flow properties. SEM images showed spherical particles with a
      smooth surface. However, hollow inner structures were observed, which may explain
      the low values of bulk density. The estimated aerodynamic diameters ranged from
      2.3 um to 8.9 um. The in silico pulmonary deposition profiles indicated, for some
      formulations, that a significant fraction of the particles would be deposited in
      the deeper lung regions. CONCLUSIONS: Statistical analysis demonstrated that not
      only drug loading but also the aerodynamic diameter of the microparticles is
      greatly affected by the preparation conditions. Overall, the results indicated
      that the low-density azithromycin-loaded microparticles with a relatively high
      respirable fraction may be obtained for the local treatment of lung infections.

PMID- 26289003
TI  - New trimethyl chitosan-based composite nanoparticles as promising antibacterial
      agents.
AB  - In the present study, densely dispersed silver nanoparticles (Ag NPs) were
      rapidly green synthesized in the presence of Rumex dentatus aqueous extract,
      followed by UV-irradiation reduction. The Ag NPs were characterized using UV-vis
      spectroscopy, FTIR, XRD, and TEM. Then, the Ag NPs were incorporated into
      interpenetrating polymeric networks based on cationic trimethyl chitosan (TMCS)
      and anionic poly(acrylamide-co-sodium acrylate) copolymer to develop a new series
      of composite nanoparticles as potential antibacterial agents. Both TMCS and
      poly(acrylamide-co-sodium acrylate) were prepared in the study, and characterized
      using FTIR, DSC, and SEM. The synthesized Ag NPs showed high purity and uniform
      particle size distribution with particle size ranged between 5 and 30 nm. The
      composite nanoparticles demonstrated homogeneous spherical shape with size in the
      range of 378-402 nm. Both Ag NPs and the composite nanoparticles showed promising
      bactericidal activity as compared with the control. Moreover, the antibacterial
      activity of the composite nanoparticles increased along with increasing the
      concentrations of Ag NPs and the TMCS. 

PMID- 26289004
TI  - Improved oral bioavailability of valsartan using proliposomes: design,
      characterization and in vivo pharmacokinetics.
AB  - The objective of our investigational work was to develop a proliposomal
      formulation to improve the oral bioavailability of valsartan. Proliposomes were
      formulated by thin film hydration technique using different ratios of
      phospholipids:drug:cholesterol. The prepared proliposomes were evaluated for
      vesicle size, encapsulation efficiency, morphological properties, in vitro drug
      release, in vitro permeability and in vivo pharmacokinetics. In vitro drug
      release studies were performed in simulated gastric fluid (pH 1.2) and purified
      water using dialysis bag method. In vitro drug permeation was studied using
      parallel artificial membrane permeation assay (PAMPA), Caco-2 monolayer and
      everted rat intestinal perfusion techniques. In vivo pharmacokinetic studies were
      conducted in male Sprague Dawley (SD) rats. Among the proliposomal formulations,
      F-V was found to have the highest encapsulation efficiency of 95.6 +/- 2.9% with
      a vesicle size of 364.1 +/- 14.9 nm. The in vitro dissolution studies indicated
      an improved drug release from proliposomal formulation, F-V in comparison to pure
      drug suspension in both, purified water and pH 1.2 dissolution media after 12 h.
      Permeability across PAMPA, Caco-2 cell and everted rat intestinal perfusion
      studies were higher with F-V formulation as compared to pure drug. Following
      single oral administration of F-V formulation, a relative bioavailability of
      202.36% was achieved as compared to pure valsartan. 

PMID- 26289005
TI  - Synthesis of a novel superdisintegrant by starch derivatization with
      polysuccinimide and its application for the development of Ondansetron fast
      dissolving tablet.
AB  - CONTEXT: Disintegrants are the key excipients administered in tablet formulations
      to boost the decomposition of the tablet into smaller pieces in the
      gastrointestinal environment, thereby increasing the available surface area and
      enhancing a more rapid release of the active ingredient. OBJECTIVE:
      Polysuccinimide (PSI), a biodegradable polymer synthesized from aspartic acid,
      was reacted with starch and fully assessed by CHN, (1)H-NMR, and FTIR. METHODS:
      PSI-grafted starch (PSI-St) was synthesized and applied as a disintegrant in the
      formulation of a rapidly disintegrating tablet of Ondansetron, a nausea and
      vomiting medicine. The tablet formulated with the newly developed
      superdisintegrant was evaluated for hardness, friability, disintegration time,
      and dissolution rate, and the results were compared with tablets formulated with
      an identical composition of test formulation differing only in type of
      disintegrant. RESULTS: Tablets prepared with starch and tablets prepared with
      sodium starch glycolate (SSG) were used as negative and positive controls,
      respectively. Dissolution study results indicated that although the onset of
      disintegration action was faster for SSG than PSI-St, higher amounts of drug were
      released from tablets formulated from PSI-St than from those formulated from SSG
      during 10 min. CONCLUSION: It was concluded that the novel synthesized
      superdisintegrant has an appropriate potential for the application in the
      formulation of fast dissolving tablets.

PMID- 26289006
TI  - Preparation of co-spray dried cushioning agent containing stearic acid for
      protecting pellet coatings when compressed.
AB  - This study investigated the applicability of stearic acid as a co-adjuvant in
      cushioning agent formulated to prevent coat damage when compressing coated
      pellets. The co-processed and physical blended fillers were prepared by spray
      drying and physically blending, respectively, with filler ingredients consisting
      of stearic acid, microcrystalline cellulose, fully gelatinized starch, and corn
      starch. Pellets containing drug were produced by coating onto non-pariels a drug
      layer of metformin followed by a sustained-release layer. Drug release from
      tablets composed of co-processed or physical blended fillers (0, 1, 5, and 10%
      stearic acid levels) and coated drug containing pellets were analyzed using
      similarity factor F2. Under the same force and the stearic acid level, co
      processed fillers produced pellet containing tablets which showed higher F2 or
      t50 values and tensile strengths as well as lower yield pressures as compared
      with tablets containing physical blended fillers. It was shown that the
      destructive degree of pellet coating was significantly reduced after being co
      processed by homogenization and the incorporation of stearic acid in the
      cushioning agents, as shown by the improved F2 and t50 values. In addition,
      disintegrate times of tablets containing co-processed agents decreased despite
      the hydrophobic stearic acid. In conclusion, the inclusion of stearic acid in co
      processed cushioning agents was effective at protecting compacted coated pellets
      from compression-induced damage without compromising disintegratability. The
      findings could serve as a step towards resolving the technical challenges of
      balancing the drug release profiles, tablet tensile strength, and disintegration
      time of compacting coated pellets into multi-particulate-sustained release
      tablets.

PMID- 26289008
TI  - Very serious and non-ignorable problem: Crisis in emergency medical response in
      catastrophic event.
AB  - The crisis of medical response caused by catastrophic events might significantly
      affect emergency response, and might even initiate more serious social crisis.
      Therefore, early identification and timely blocking the formation of crisis in
      the early phase after a major disaster will improve the efficiency of medical
      response in a major disaster and avoid serious consequences. In the present
      paper, we described the emergency strategy to crisis management of medical
      response after a major disaster. Major catastrophic events often lead to various
      crises, including excess demand, the crisis of response in barrier and the
      structural crisis in response. The corresponding emergency response strategies
      include: (i) shunt of catastrophic medical surge; (ii) scalability of medical
      surge capacity; (iii) matching of the structural elements of response; (iv)
      maintaining the functions of support system for medical response and maximising
      the operation of the integrated response system; and (v) selection of appropriate
      care 'standard' in extreme situations of overload of disaster medical surge. In
      conclusion, under the impact of a major catastrophic event, medical response is
      often complex and the medical surge beyond the conventional response capacity and
      it is easy to be in crisis. In addition to the current consensus of disaster
      response, three additional aspects should be considered. First, all relevant
      society forces led by the government and military should be linkages. Second, a
      powerful medical response system must be based on a strong support system. Third,
      countermeasures of medical surge should be applied flexibly to the special and
      specific disaster environment, to promote the effective medical response force.

PMID- 26289007
TI  - Infrared Thermography in Dogs with Mammary Tumors and Healthy Dogs.
AB  - BACKGROUND: Infrared thermography is a painless, noninvasive, nonionizing
      diagnostic imaging exam used in human medicine as an auxiliary tool for breast
      cancer diagnosis in women. HYPOTHESIS/OBJECTIVES: Define thermographic mean
      temperatures of healthy mammary glands and compare these temperatures with those
      of mammary glands with tumors in dogs. ANIMALS: Fifty client-owned female dogs
      were evaluated, including 20 with histopathologically confirmed mammary tumor and
      30 clinically healthy (control). METHODS: A randomized study using infrared
      thermography analyzed each mammary gland of the animals from the control group
      and mammary glands with tumors from the tumor group, then the thermographic
      temperatures obtained were compared. Thermographic exam was performed in a
      temperature-controlled room with a cooled thermographic camera-Flir E-40 (Flir
      Systems((r)) ) RESULTS: There was significantly a higher temperature in the
      caudal abdominal and inguinal mammary glands than the other glands in the healthy
      group (P < .05). Dogs with mammary tumors had significantly higher thermographic
      temperature compared with unaffected glands regardless of the tumor size and the
      location (P < .05). CONCLUSIONS AND CLINICAL IMPORTANCE: The technique seems to
      be able to assess for the presence of neoplasia within the mammary tissue in
      bitches. Further investigation is necessary to determine the impact of this
      technique when adopted clinically.

PMID- 26289009
TI  - Keep an ear to the ground, the answer's behind.

PMID- 26289011
TI  - Outcome prediction, fluid resuscitation, pain management, and antibiotic
      prophylaxis in severe acute pancreatitis.

PMID- 26289010
TI  - Is empiric daptomycin effective in reducing mortality in Staphylococcus aureus
      bacteraemia? A real-life experience.

PMID- 26289012
TI  - Understanding recruitment maneuvers.

PMID- 26289013
TI  - Does this patient have acute kidney injury? An AKI checklist.

PMID- 26289014
TI  - Understanding antibiotic stewardship for the critically ill.

PMID- 26289015
TI  - Rapid development and rupture of a cerebral mycotic aneurysm in Candida infective
      endocarditis.

PMID- 26289016
TI  - Highly Efficient Phosphate Scavenger Based on Well-Dispersed La(OH)3 Nanorods in
      Polyacrylonitrile Nanofibers for Nutrient-Starvation Antibacteria.
AB  - La(OH)3 nanorods immobilized in polyacrylonitrile (PAN) nanofibers (PLNFs) were
      fabricated for the first time by electrospinning and a subsequent in situ
      surfactant-free precipitation method and then applied as a highly efficient
      phosphate scavenger to realize nutrient-starvation antibacteria for drinking
      water security. The immobilization by PAN nanofibers effectively facilitated the
      in situ formation of the aeolotropic and well-dispersed La(OH)3 nanostructures
      and, thus, rendered higher phosphate removal efficiency due to more exposed
      active sites for binding phosphate. The maximum phosphate capture capacity of
      La(OH)3 nanorods in PAN nanofibers was around 8 times that of the La(OH)3
      nanocrystal fabricated by precipitation without PAN protection. Moreover,
      remarkably fast adsorption kinetics and high removal rate were observed toward
      low concentration phosphate due to the high activity of our materials, which can
      result in a stringent phosphate-deficient condition to kill microorganisms in
      water effectively. The present material is also capable of preventing sanitized
      water from recontamination by bacteria and keeping water biologically stable for
      drinking. Impressively, stabilized by PAN nanofibers, the La(OH)3 nanorods can be
      easily separated out after reactions and avoid leaking into water. The present
      development has great potential as a promising antimicrobial solution for
      practical drinking water security and treatment with a negligible environmental
      footprint. 

PMID- 26289017
TI  - Breaking the species barrier for hepatitis delta virus.

PMID- 26289019
TI  - Research misconduct and data fraud in clinical trials: prevalence and causal
      factors.
AB  - The disclosure of cases of research misconduct in clinical trials, conventionally
      defined as fabrication, falsification or plagiarism, has been a disturbingly
      common phenomenon in recent years. Such cases can potentially harm patients
      enrolled on the trials in question or patients treated based on the results of
      those trials and can seriously undermine the scientific and public trust in the
      validity of clinical trial results. Here, I review what is known about the
      prevalence of research misconduct in general and the contributing or causal
      factors leading to the misconduct. The evidence on prevalence is unreliable and
      fraught with definitional problems and with study design issues. Nevertheless,
      the evidence taken as a whole seems to suggest that cases of the most serious
      types of misconduct, fabrication and falsification (i.e., data fraud), are
      relatively rare but that other types of questionable research practices are quite
      common. There have been many individual, institutional and scientific factors
      proposed for misconduct but, as is the case with estimates of prevalence,
      reliable empirical evidence on the strength and relative importance of these
      factors is lacking. However, it seems clear that the view of misconduct as being
      simply the result of aberrant or self-delusional personalities likely
      underestimates the effect of other important factors and inhibits the development
      of effective prevention strategies. 

PMID- 26289020
TI  - A Comparison of Polysaccharide Substrates and Reducing Sugar Methods for the
      Measurement of endo-1,4-beta-Xylanase.
AB  - The most commonly used method for the measurement of the level of endo-xylanase
      in commercial enzyme preparations is the 3,5-dinitrosalicylic acid (DNS) reducing
      sugar method with birchwood xylan as substrate. It is well known that with the
      DNS method, much higher enzyme activity values are obtained than with the Nelson
      Somogyi (NS) reducing sugar method. In this paper, we have compared the DNS and
      NS reducing sugar assays using a range of xylan-type substrates and accurately
      compared the molar response factors for xylose and a range of xylo
      oligosaccharides. Purified beechwood xylan or wheat arabinoxylan is shown to be a
      suitable replacement for birchwood xylan which is no longer commercially
      available, and it is clearly demonstrated that the DNS method grossly
      overestimates endo-xylanase activity. Unlike the DNS assay, the NS assay gave the
      equivalent colour response with equimolar amounts of xylose, xylobiose,
      xylotriose and xylotetraose demonstrating that it accurately measures the
      quantity of glycosidic bonds cleaved by the endo-xylanase. The authors strongly
      recommend cessation of the use of the DNS assay for measurement of endo-xylanase
      due to the fact that the values obtained are grossly overestimated due to
      secondary reactions in colour development. 

PMID- 26289021
TI  - Gender, race, BMI, and social support in relation to the health-related quality
      of life of cancer survivors: a report from the American Cancer Society's Study of
      Cancer Survivors II (SCS-II).
AB  - PURPOSE: We examined the main and interactive effects of race, BMI, and social
      support on physical and mental health-related quality of life (HRQoL) among male
      and female cancer survivors using the stress and coping theory to inform
      findings. METHODS: HRQoL issues among 1768 cancer survivors were examined using
      the American Cancer Society's cross-sectional Study of Cancer Survivors II. Two
      step multiple linear regressions were conducted to assess the physical and mental
      HRQoL of male and female cancer survivors, respectively. RESULTS: The average age
      of participants was 67.36 (SD = 11.51); the majority were female (53.3 %; n =
      941) and non-Hispanic White (85.9 %; n = 1517). The average BMI measurement for
      participants was 28.33 (SD = 5.90), with 41.3 % (n = 729) overweight and 30.3 %
      (n = 535) obese. Higher BMI was significantly associated with lower physical
      HRQoL across gender, while social support had significant main effects on
      physical and mental HRQoL across gender. Race moderated the relationship between
      social support and physical HRQoL among female cancer survivors and between BMI
      and mental HRQoL for both genders. CONCLUSIONS: The results of this study
      contribute a unique gender- and racial-specific perspective to cancer
      survivorship research. While the buffering hypothesis of the stress and coping
      theory was not supported, the main effects of BMI and social support on HRQoL
      were different across gender and race.

PMID- 26289023
TI  - Well-being and environmental quality: Does pollution affect life satisfaction?
AB  - PURPOSE: We aimed to explore the effect of ambient air pollution on individual
      persons' levels of subjective well-being. Our research question was: to what
      extent is an individual's life satisfaction shaped by exposure to PM10? METHODS:
      We used regression models to analyse data on subjective well-being indicators
      from the last two waves of the European social survey (ESS) and detailed
      information on local levels of the air pollutant PM10. RESULTS: An increase in
      PM10 annual concentrations by 1 MUg/m(3) was associated with a significant
      reduction in life satisfaction of .017 points on the ESS 10-point life
      satisfaction scale. CONCLUSIONS: Our findings suggest that even in cases of
      relatively low levels of PM10 air pollution (mean annual concentration of 8.3 +/-
      3.9 MUg/m(3)), in addition to the effects on physical health, exposure negatively
      affects subjective assessments of well-being.

PMID- 26289022
TI  - Psychosocial profile of pediatric brain tumor survivors with neurocognitive
      complaints.
AB  - PURPOSE: With more children surviving a brain tumor, neurocognitive consequences
      of the tumor and its treatment become apparent, which could affect psychosocial
      functioning. The present study therefore aimed to assess psychosocial functioning
      of pediatric brain tumor survivors (PBTS) in detail. METHODS: Psychosocial
      functioning of PBTS (8-18 years) with parent-reported neurocognitive complaints
      was compared to normative data on health-related quality of life (HRQOL), self
      esteem, psychosocial adjustment, and executive functioning (one-sample t tests)
      and to a sibling control group on fatigue (independent-samples t test). Self-,
      parent-, and teacher-report questionnaires were included, where appropriate,
      providing complementary information. RESULTS: Eighty-two PBTS (mean age 13.4
      years, SD 3.2, 49 % males) and 43 healthy siblings (mean age 14.3, SD 2.4, 40 %
      males) were included. As compared to the normative population, PBTS themselves
      reported decreased physical, psychological, and generic HRQOL (d = 0.39-0.62, p <
      0.008). Compared to siblings, increased fatigue-related concentration problems (d
      = 0.57, p < 0.01) were reported, although self-reported self-esteem and
      psychosocial adjustment seemed not to be affected. Parents of PBTS reported more
      psychosocial (d = 0.81, p < 0.000) and executive problems (d = 0.35-0.43, p <
      0.016) in their child than parents of children in the normative population.
      Teachers indicated more psychosocial adjustment problems for female PBTS aged 8
      11 years than for the female normative population (d = 0.69, p < 0.025), but they
      reported no more executive problems. CONCLUSIONS: PBTS with parent-reported
      neurocognitive complaints showed increased psychosocial problems, as reported by
      PBTS, parents, and teachers. IMPLICATIONS FOR CANCER SURVIVORS: Systematic
      screening of psychosocial functioning is necessary so that tailored support from
      professionals can be offered to PBTS with neurocognitive complaints.

PMID- 26289024
TI  - Gene diagnosis and prenatal genetic diagnosis of a case of dystrophic
      epidermolysis bullosa family caused by gonadosomatic mosaicism for the COL7A1
      mutation p.Gly2043Arg in the pregnant mother.

PMID- 26289025
TI  - Understanding readmission to psychiatric hospital in Australia from the service
      users' perspective: a qualitative study.
AB  - Inpatient care is integral to balanced mental health systems, contributing to
      containment of risk associated with psychiatric crises and affording
      opportunities for treatment. However, psychiatric wards are not always safe and
      service users are often dissatisfied with the experience. Hence, and because
      inpatient care is the most costly component of mental health systems, minimising
      duration of admission and reducing risk of readmission are clinical and strategic
      priorities internationally. With (primarily quantitative) research to date
      focused on explaining readmission in terms of characteristics of individuals and
      services, understanding of the 'revolving door phenomenon' remains limited.
      Considering verstehen critical to addressing this messy problem, we examined
      readmission from the service users' perspective. Using grounded theory
      techniques, we inductively analysed data from interviews with 13 people
      readmitted to inpatient care within 28 days of discharge. Participants, including
      eight men, were recruited in 2013 from three psychiatric wards at a metropolitan
      hospital in Australia. Analysis supported description of readmission as a
      process, fundamentally related to insufficiency of internal, interpersonal and/or
      environmental resources to maintain community tenure. For the people in this
      study, admission to hospital was either the default coping mechanism or the
      culmination of counter-productive attempts to manage stressful circumstances.
      Readmission can appropriately be understood as one representation of a
      fundamental social malaise and the struggle of some people to survive in an
      apparently inhospitable world. The findings indicate that neither locating the
      'problem of readmission' within an individual and promoting self-governance/self
      control/self-regulation, nor identifying failures of specific services or sectors
      are likely to support the economic and ethical imperative of reducing psychiatric
      admissions. The findings of the study and limitations related to its conduct in a
      particular setting provide fertile ground for further research and design of
      interventions to break the readmission cycle. However, balanced, mental health
      services alone are insufficient; systems of care must become 'recovery oriented'.

PMID- 26289026
TI  - MT1-MMP recognition by ERM proteins and its implication in CD44 shedding.
AB  - Membrane type 1-matrix metalloproteinase (MT1-MMP) is a key enzyme involved in
      tumor cell invasion by shedding their cell-surface receptor CD44 anchored with F
      actin through ezrin/radixin/moesin (ERM) proteins. We found the cytoplasmic tail
      of MT1-MMP directly binds the FERM domain of radixin, suggesting F-actin-based
      recruitment of MT1-MMP to CD44 for invasion. Our crystal structure shows that the
      central region of the MT1-MMP cytoplasmic tail binds subdomain A of the FERM
      domain, and makes an antiparallel beta-beta interaction with beta2A-strand. This
      binding mode is distinct from the previously determined binding mode of CD44 to
      subdomain C. We showed that radixin simultaneously binds both MT1-MMP and CD44,
      indicating ERM protein-mediated colocalization of MT1-MMP and its substrate CD44
      and anchoring to F-actin. Our study implies that ERM proteins contribute toward
      accelerated CD44 shedding by MT1-MMP through ERM protein-mediated interactions
      between their cytoplasmic tails. 

PMID- 26289027
TI  - Validation of the Psychometric Properties of the Self-Compassion Scale. Testing
      the Factorial Validity and Factorial Invariance of the Measure among Borderline
      Personality Disorder, Anxiety Disorder, Eating Disorder and General Populations.
AB  - BACKGROUND: During the last years, there has been a growing interest in self
      compassion. Empirical evidences show that self-compassion is associated with
      psychological benefits among young adults and it might be considered a buffer
      factor in several mental disorders. AIMS: The aim of this study was to validate
      the psychometric properties of the Self-compassion Scale (SCS: Neff, 2003a) after
      the initial lack of replicating the original six-factor structure. METHOD: Data
      were collected from the overall database of a research centre (56 men and 305
      women; mean age = 25.19) and comprised four groups: borderline personality
      disorder, anxiety disorder, eating disorder and general population. RESULTS:
      Confirmatory factor analysis supported a two-factor model (self-compassionate
      attitude versus self-critical attitude) with good internal consistencies,
      construct-related validity and external validity. Configural, weak measurement
      and structural invariance of the two-factor model of SCS were also shown.
      CONCLUSIONS: Findings support the generalizability of the two-factor model and
      show that both properties and interpretations of scores on self-compassion are
      equivalent across these population groups. Copyright (c) 2015 John Wiley & Sons,
      Ltd. KEY PRACTITIONER MESSAGE: A two-factor structure of SCS with strong
      psychometric validity was supported in clinical and non-clinical samples. Helping
      individuals with limited experiences of compassion to develop positive internal
      processing systems seems to be related with better mental health, self-acceptance
      and self-nurturing abilities. The non-probabilistic sampling limits the
      generalization of our conclusions.

PMID- 26289028
TI  - A set of homo-oligomeric standards allows accurate protein counting.
AB  - Techniques based on fluorescence microscopy are increasingly used to count
      proteins in cells, but few stoichiometrically well-defined standards are
      available to test their accuracy. A selection of bacterial homo-oligomers were
      developed that contain 10-24 subunits and fully assemble when expressed in
      mammalian cells, and they can be used to easily validate/calibrate molecular
      counting methods. The utility of these standards was demonstrated by showing that
      nuclear pores contain 32 copies of the Nup107 complex. 

PMID- 26289029
TI  - High-resolution three-dimensional digital imaging of the human renal
      microcirculation: An aid to evaluating microvascular alterations in chronic
      kidney disease in humans.
AB  - We have developed a new virtual microscopy method, with two- and three
      dimensional (2D, 3D) synchronization, that enables visualization of the human
      renal microvasculature. The method was used to evaluate 120-150 serially cut
      sections of paraffin-embedded human renal tissue from nephrectomized samples.
      Virtual microscopy images of sections double-immunostained with antibodies
      against CD34 (an endothelium marker) and smooth muscle actin (an arterial media
      marker) and stained with periodic acid-Schiff were processed using digital
      imaging analysis software. Image registration was conducted to generate 3D
      displays with red-green-blue color segmentation. The reconstructed images of the
      microvasculature, including the interlobular arteries and the glomeruli, allowed
      visualization of 3D structures and direct glomerular connections. Synchronizing
      these 3D images with the corresponding 2D images revealed the relationships
      between arteriosclerotic lesions and downstream glomeruli. Thus, interlobular
      arteries with moderate intimal thickening and afferent arterioles with segmental
      hyalinosis/sclerosis, as seen on the 2D images, exhibited wall irregularities on
      the corresponding 3D images. However, these lesions were not directly influenced
      by lesions in downstream glomeruli, such as sclerotic lesions. Our virtual-slide
      method based on 2D and 3D image synchronization provides a comprehensive view of
      the renal microcirculation and therefore novel insights into the pathogenesis of
      vascular-associated renal diseases. 

PMID- 26289030
TI  - Exploring youth and caregiver preferences for asthma education video content.
AB  - OBJECTIVE: This study examines (1) whether youth and their caregivers have
      different preferences for asthma education video topics and (2) if education
      topic preferences vary by youth and caregiver sociodemographic characteristics.
      METHODS: Youth (n = 83) ages 7-17 years with persistent asthma and their
      caregivers were recruited at two pediatric practices in North Carolina.
      Sociodemographic information and youth and caregiver preferences for nine asthma
      video education topics were collected during in-person interviews. Bonferroni
      corrected Chi-square or McNemar tests (alpha = 0.0056) were used to compare youth
      and caregivers differences in topic preferences and topic preferences by youth
      and caregiver sociodemographic characteristics, including gender, race,
      ethnicity, and age. RESULTS: Youth were primarily male (52%) and from low-income
      families (74%; caregiver annual income less than $30,000) and many were Hispanic
      (45%). Youth and parents expressed the most interest in the following two topics:
      "how to deal with triggers" (90% and 95%, respectively) and "how to keep asthma
      under control" (87% and 96%, respectively). Caregivers and children were
      discordant for two topics: "the difference between a rescue and controller
      medicine" and "how to [help your child] talk to your [his/her] friends about
      asthma." No differences were found between youth and caregiver sociodemographic
      characteristics and video topic preferences. CONCLUSIONS: Youth with persistent
      asthma and their caregivers differed in their asthma education topic preferences,
      but preferences did not vary by caregiver or youth sociodemographic
      characteristics. Studies examining the effectiveness of interventions tailored to
      differences in educational preferences of youth with asthma and their caregivers
      are needed.

PMID- 26289032
TI  - Creating a completely "cell-free" system for protein synthesis.
AB  - Cell-free protein synthesis is a promising tool to take biotechnology outside of
      the cell. A cell-free approach provides distinct advantages over in vivo systems
      including open access to the reaction environment and direct control over all
      chemical components for facile optimization and synthetic biology integration.
      Promising applications of cell-free systems include portable diagnostics,
      biotherapeutics expression, rational protein engineering, and biocatalyst
      production. The highest yielding and most economical cell-free systems use an
      extract composed of the soluble component of lysed Escherichia coli. Although E.
      coli lysis can be highly efficient (>99.999%), one persistent challenge is that
      the extract remains contaminated with up to millions of cells per mL. In this
      work, we examine the potential of multiple decontamination strategies to further
      reduce or eliminate bacteria in cell-free systems. Two strategies, sterile
      filtration and lyophilization, effectively eliminate contaminating cells while
      maintaining the systems' protein synthesis capabilities. Lyophilization provides
      the additional benefit of long-term stability at storage above freezing.
      Technologies for personalized, portable medicine and diagnostics can be expanded
      based on these foundational sterilized and completely "cell-free" systems.

PMID- 26289034
TI  - The Effect of Elapsed Time from Myocardial Infarction on Mortality and Major
      Adverse Cardiac and Cerebrovascular Events in ICD Patients.
AB  - BACKGROUND: Despite the effectiveness of implantable cardioverter defibrillator
      (ICD) therapy in reducing mortality, the optimal timing of ICD implantation after
      myocardial infarction (MI) remains inconclusive. The aim of this study is to
      evaluate the association of elapsed time from MI to ICD implantation on mortality
      and major adverse cardiac and cerebrovascular events (MACCEs) in patients with
      prior MI. METHODS: We studied 974 patients who underwent a first ICD implantation
      between October 1998 and August 2011. The median time from MI to ICD implantation
      was 7.2 years. Elapsed time from MI to ICD was categorized into tertiles (<2.5
      years, 2.5-12.1 years, >12.1 years). Additionally, the time from most recent MI
      to ICD implantation was dichotomized at 18 months. RESULTS: During a median
      follow-up of 3.4 years, 287 patients died. Cumulative mortality rates at 3 years,
      5 years, and 8 years were 19%, 29%, 47%, respectively. In univariate analysis,
      there was a significant difference in mortality for patients in the highest
      tertile compared to those in the lowest tertile (hazard ratio: 1.50; 95%
      confidence interval: 1.12-2.02; P = 0.007). After adjusting for baseline
      characteristics, there was no association between time from MI and mortality. At
      8-year follow-up, the cumulative MACCE rate excluding mortality was 22%. No
      association between time from MI and MACCE was found. CONCLUSION: In this study,
      we found no association between the elapsed time from MI to ICD implantation and
      8-year all-cause mortality or MACCE in post-MI ICD patients.

PMID- 26289033
TI  - The Role of Scleraxis in Fate Determination of Mesenchymal Stem Cells for
      Tenocyte Differentiation.
AB  - Mesenchymal stem cells (MSCs) are pluripotent cells that primarily differentiate
      into osteocytes, chondrocytes, and adipocytes. Recent studies indicate that MSCs
      can also be induced to generate tenocyte-like cells; moreover, MSCs have been
      suggested to have great therapeutic potential for tendon pathologies. Yet the
      precise molecular cascades governing tenogenic differentiation of MSCs remain
      unclear. We demonstrate scleraxis, a transcription factor critically involved in
      embryonic tendon development and formation, plays a pivotal role in the fate
      determination of MSC towards tenocyte differentiation. Using murine C3H10T1/2
      pluripotent stem cells as a model system, we show scleraxis is extensively
      expressed in the early phase of bone morphogenetic protein (BMP)-12-triggered
      tenocytic differentiation. Once induced, scleraxis directly transactivates tendon
      lineage-related genes such as tenomodulin and suppresses osteogenic,
      chondrogenic, and adipogenic capabilities, thus committing C3H10T1/2 cells to
      differentiate into the specific tenocyte-like lineage, while eliminating
      plasticity for other lineages. We also reveal that mechanical loading-mediated
      tenocytic differentiation follows a similar pathway and that BMP-12 and cyclic
      uniaxial strain act in an additive fashion to augment the maximal response by
      activating signal transducer Smad8. These results provide critical insights into
      the determination of multipotent stem cells to the tenocyte lineage induced by
      both chemical and physical signals. 

PMID- 26289035
TI  - Congenital Malformations Associated With a Single Umbilical Artery in Twin
      Pregnancies.
AB  - A single umbilical artery (SUA) was identified in 1.5% of twin pregnancies. The
      presence of a SUA in a twin pregnancy was associated with a 50% incidence of
      fetal anomalies, many of them complex and severe. The embryology and
      pathophysiological mechanisms associated with a SUA are reviewed. Aneuploidy is
      relatively common and should be considered, particularly in the presence of
      associated anomalies. Fetal growth restriction is frequent and preterm delivery
      is common. 

PMID- 26289036
TI  - Purkinje Cells as Sources of Arrhythmias in Long QT Syndrome Type 3.
AB  - Long QT syndrome (LQTS) is characterized by ventricular arrhythmias and sudden
      cardiac death. Purkinje cells (PC) within the specialized cardiac conduction
      system have unique electrophysiological properties that we hypothesize may
      produce the primary sources of arrhythmia in heritable LQTS. LQTS type 3 (LQT3)
      transgenic mice harboring the DeltaKPQ(+/-) mutation were crossed with Contactin2
      EGFP BAC transgenic mice, which express a fluorescent reporter gene within the
      Purkinje fiber network. Isolated ventricular myocytes (VMs) (EGFP(-)) and PCs
      (EGFP(+)) from wild type and DeltaKPQ mutant hearts were compared using the whole
      cell patch clamp technique and microfluorimetry of calcium transients. Increased
      late sodium current was seen in DeltaKPQ-PCs and DeltaKPQ-VMs, with larger
      density in DeltaKPQ-PCs. Marked prolongation of action potential duration of
      DeltaKPQ-PCs was seen compared to DeltaKPQ-VMs. DeltaKPQ-PCs, but not DeltaKPQ
      VMs, exhibited frequent early afterdepolarizations, which corresponded to
      repetitive oscillations of intracellular calcium. Abnormalities in cell
      repolarization were reversed with exposure to mexiletine. We present the first
      direct experimental evidence that PCs are uniquely sensitive to LQT3 mutations,
      displaying electrophysiological behavior that is highly pro-arrhythmic. 

PMID- 26289037
TI  - Computational and spectroscopic data correlation study of N,N'-bisarylmalonamides
      (Part II).
AB  - To complement a previous UV study, we present a quantitative evaluation of
      substituent effects on spectroscopic data ((1)H and (13)C NMR chemical shifts as
      well as FT-IR absorption frequency) applied to N,N'-bisarylmalonamides, using
      simple and extended Hammett equations as well as the Swain-Lupton equation.
      Furthermore, the DFT CAM-B3LYP/6-311+G(d,p) method was applied to study the
      impact of different solvents on the geometry of the molecules and their spectral
      data. Additionally, experimental data are correlated with theoretical results;
      excellent linear dependence was obtained. The overall results presented in this
      paper show that N,N'-bisarylmalonamides are prominent candidates for model
      molecules.

PMID- 26289038
TI  - Continuous-wave near-infrared spectroscopy is not related to brain tissue oxygen
      tension.
AB  - Near-infrared spectroscopy (NIRS) has gained acceptance for cerebral monitoring,
      especially during cardiac surgery, though there are few data showing its
      validity. We therefore aimed to correlate invasive brain tissue oxygen
      measurements (PtiO2) with the corresponding NIRS-values (regional oxygen
      saturation, rSO2). We also studied whether NIRS was able to detect ischemic
      events, defined as a PtiO2-value of <15 mmHg. Eleven patients were studied with
      invasive brain tissue oxygen monitoring and continuous-wave NIRS. PtiO2
      correlation with corresponding NIRS-values was calculated. We found no
      correlation between PtiO2- and NIRS-readings. Measurement of rSO2 was no better
      than flipping a coin in the detection of cerebral ischemia when a commonly agreed
      ischemic PtiO2 cut-off value of <15 mmHg was chosen. Continuous-wave-NIRS was
      unable to reliably detect ischemic cerebral episodes, defined as a PtiO2 value
      <15 mmHg. Displayed NIRS-values did not correlate with invasively measured PtiO2
      values. CW-NIRS should not be used for the detection of cerebral ischemia. 

PMID- 26289039
TI  - Evaluation of behavioral outcomes in children 1 year after epilepsy surgery.
AB  - OBJECTIVE: Children with epilepsy have elevated rates of behavior problems.
      Research findings on the impact of epilepsy surgery on children's behavior have
      been mixed, with some studies showing improvements in behavior 3 to 18 months
      after surgery and other studies finding no change within this time interval. We
      examined behavior in a large surgical sample and in a nonsurgical comparison
      group. We also examined for potential effects of epilepsy-related and
      cognitive/linguistic variables. METHODS: Behavior was assessed by parent report
      in 147 children who underwent epilepsy surgery and 40 children who did not, using
      the Child Behavior Checklist (CBCL). For the surgical group, the CBCL was
      completed prior to surgery (baseline) and approximately 1 year after surgery
      (follow-up); ratings of the nonsurgical group were also conducted twice, at
      comparable intervals. RESULTS: At baseline, the groups did not differ on age,
      sex, age at seizure onset, antiepileptic drugs (AEDs), or intelligence quotient
      (IQ). Baseline Social and Attention Problems were higher in the nonsurgical
      group. At follow-up, 65% of the surgical group and 20% of the nonsurgical group
      were seizure-free. Behavioral change was not related to surgical status or
      seizure outcome. Children with temporal lobe seizure focus had more Externalizing
      Behaviors compared to those with frontal or multilobar foci. Attention was poorer
      in children who underwent frontal lobe excisions relative to temporal or
      multilobar excisions. Baseline IQ did not predict behavioral change.
      SIGNIFICANCE: Our results suggest that surgery and seizure outcome do not affect
      behavior in the first year following surgery; it may be the abnormal neural
      substrate and not seizure control that influences behavior in children with
      epilepsy. If changes are to occur due to seizure freedom, they may require a
      longer time to emerge. Some behaviors may be resistant to change in children with
      epilepsy or may require even longer intervals for improvement.

PMID- 26289040
TI  - Hypofractionated irradiation of infra-supraclavicular lymph nodes after axillary
      dissection in patients with breast cancer post-conservative surgery: impact on
      late toxicity.
AB  - BACKGROUND: The aim of the present work was to analyse the impact of mild
      hypofractionated radiotherapy (RT) of infra-supraclavicular lymph nodes after
      axillary dissection on late toxicity. METHODS: From 2007 to 2012, 100 females
      affected by breast cancer (pT1- T4, pN1-3, pMx) were treated with conservative
      surgery, Axillary Node Dissection (AND) and loco-regional radiotherapy (whole
      breast plus infra-supraclavicular fossa). Axillary lymph nodes metastases were
      confirmed in all women. The median age at diagnosis was 60 years (range 34-83).
      Tumors were classified according to molecular characteristics: luminal-A 59 pts
      (59%), luminal-B 24 pts (24%), basal-like 10 pts (10%), Her-2 like 7 pts (7%). 82
      pts (82%) received hormonal therapy, 9 pts (9%) neo-adjuvant chemotherapy, 81pts
      (81%) adjuvant chemotherapy. All patients received a mild hypofractionated RT: 46
      Gy in 20 fractions 4 times a week to whole breast and infra-supraclavicular fossa
      plus an additional weekly dose of 1,2 Gy to the lumpectomy area. The disease
      control and treatment related toxicity were analysed in follow-up visits. The
      extent of lymphedema was analysed by experts in Oncological Rehabilitation.
      RESULTS: Within a median follow-up of 50 months (range 19-82), 6 (6%) pts died, 1
      pt (1%) had local progression disease, 2 pts (2%) developed distant metastasis
      and 1 subject (1%) presented both. In all patients the acute toxicity was mainly
      represented by erythema and patchy moist desquamation. At the end of radiotherapy
      27 pts (27%) presented lymphedema, but only 10 cases (10%) seemed to be
      correlated to radiotherapy. None of the patients showed a severe damage to the
      brachial plexus, and the described cases of paresthesias could not definitely be
      attributed to RT. We did not observe symptomatic pneumonitis. CONCLUSIONS:
      Irradiation of infra-supraclavicular nodes with a mild hypofractionated schedule
      can be a safe and effective treatment without evidence of a significant increase
      of lymphedema appearance radiotherapy related.

PMID- 26289041
TI  - POPE: post optimization posterior evaluation of likelihood free models.
AB  - BACKGROUND: In many domains, scientists build complex simulators of natural
      phenomena that encode their hypotheses about the underlying processes. These
      simulators can be deterministic or stochastic, fast or slow, constrained or
      unconstrained, and so on. Optimizing the simulators with respect to a set of
      parameter values is common practice, resulting in a single parameter setting that
      minimizes an objective subject to constraints. RESULTS: We propose algorithms for
      post optimization posterior evaluation (POPE) of simulators. The algorithms
      compute and visualize all simulations that can generate results of the same or
      better quality than the optimum, subject to constraints. These optimization
      posteriors are desirable for a number of reasons among which are easy
      interpretability, automatic parameter sensitivity and correlation analysis, and
      posterior predictive analysis. Our algorithms are simple extensions to an
      existing simulation-based inference framework called approximate Bayesian
      computation. POPE is applied two biological simulators: a fast and stochastic
      simulator of stem-cell cycling and a slow and deterministic simulator of tumor
      growth patterns. CONCLUSIONS: POPE allows the scientist to explore and understand
      the role that constraints, both on the input and the output, have on the
      optimization posterior. As a Bayesian inference procedure, POPE provides a
      rigorous framework for the analysis of the uncertainty of an optimal simulation
      parameter setting.

PMID- 26289042
TI  - Response to: 'Body mass index and the risk of rheumatoid arthritis: a systematic
      review and dose-response meta-analysis'--authors' reply.

PMID- 26289043
TI  - DCP-LA Activates Cytosolic PKCepsilon by Interacting with the Phosphatidylserine
      Binding/Associating Sites Arg50 and Ile89 in the C2-Like Domain.
AB  - BACKGROUND/AIMS: The linoleic acid derivative DCP-LA selectively and directly
      activates PKCepsilon. The present study aimed at understanding the mechanism of
      DCP-LA-induced PKCepsilon activation. METHODS: Point mutation in the C2-like
      domain on PKCepsilon was carried out, and each kinase activity was monitored in
      PC-12 cells using a foerster resonance energy transfer (FRET) probe with cyan
      fluorescent protein (CFP) and yellow fluorescent protein (YFP) at the N- and C
      terminal ends of PKCepsilon, respectively, or in the cell-free systems using a
      reversed phase high-performance liquid chromatography (HPLC). Intracellular
      PKCepsilon mobilization was monitored in PC-12 cells using mRuby-conjugated
      PKCepsilon. DCP-LA binding to PKCepsilon was assayed using a fluorescein
      conjugated to DCP-LA at the carboxyl-terminal end (Fluo-DCP). Uptake of DCP-LA
      into cells was measured in PC-12 ells. RESULTS: In the FRET analysis, DCP-LA
      decreased the ratio of YFP signal intensity/CFP signal intensity in PC-12 cells
      and in the cell-free kinase assay, DCP-LA increased area of phosphorylated PKC
      substrate peptide, indicating DCP-LA-induced PKCepsilon activation. These effects
      were significantly suppressed by replacing Arg50 and Ile89 by Ala or Asn in the
      C2-like domain of PKCepsilon. In the fluorescent cytochemistry, DCP-LA did not
      affect intracellular PKCepsilon distribution. In the cell-free binding assay,
      Fluo-DCP, that had no effect on the potential for PKCepsilon activation, bound to
      PKCepsilon, and the binding was inhibited only by mutating Ile89. Extracellularly
      applied DCP-LA was taken up into cells in a concentration-dependent manner.
      Although no activation was obtained in the cell-free kinase assay, the broad PKC
      activator PMA activated PKCepsilon in PC-12 cells in association with
      translocation towards the cell surface, which was inhibited by mutating I89A.
      CONCLUSION: Unlike PMA DCP-LA activates cytosolic PKCepsilon by binding to the
      phosphatidylserine binding/associating sites Arg50 and Ile89, possibly at the
      carboxyl-terminal end and the cyclopropane rings, respectively.

PMID- 26289044
TI  - Available nitrogen is the key factor influencing soil microbial functional gene
      diversity in tropical rainforest.
AB  - BACKGROUND: Tropical rainforests cover over 50% of all known plant and animal
      species and provide a variety of key resources and ecosystem services to humans,
      largely mediated by metabolic activities of soil microbial communities. A deep
      analysis of soil microbial communities and their roles in ecological processes
      would improve our understanding on biogeochemical elemental cycles. However, soil
      microbial functional gene diversity in tropical rainforests and causative factors
      remain unclear. GeoChip, contained almost all of the key functional genes related
      to biogeochemical cycles, could be used as a specific and sensitive tool for
      studying microbial gene diversity and metabolic potential. In this study, soil
      microbial functional gene diversity in tropical rainforest was analyzed by using
      GeoChip technology. RESULTS: Gene categories detected in the tropical rainforest
      soils were related to different biogeochemical processes, such as carbon (C),
      nitrogen (N) and phosphorus (P) cycling. The relative abundance of genes related
      to C and P cycling detected mostly derived from the cultured bacteria. C
      degradation gene categories for substrates ranging from labile C to recalcitrant
      C were all detected, and gene abundances involved in many recalcitrant C
      degradation gene categories were significantly (P < 0.05) different among three
      sampling sites. The relative abundance of genes related to N cycling detected was
      significantly (P < 0.05) different, mostly derived from the uncultured bacteria.
      The gene categories related to ammonification had a high relative abundance. Both
      canonical correspondence analysis and multivariate regression tree analysis
      showed that soil available N was the most correlated with soil microbial
      functional gene structure. CONCLUSIONS: Overall high microbial functional gene
      diversity and different soil microbial metabolic potential for different
      biogeochemical processes were considered to exist in tropical rainforest. Soil
      available N could be the key factor in shaping the soil microbial functional gene
      structure and metabolic potential.

PMID- 26289046
TI  - Effect of nutrition care provided by primary health professionals on adults'
      dietary behaviours: a systematic review.
AB  - BACKGROUND: 'Nutrition care' refers to any practice conducted by a health
      professional to support a patient to improve their dietary behaviours. Better
      understanding about the effectiveness of nutrition care is required to identify
      ways to enhance success of future interventions. OBJECTIVE: Systematically review
      literature that investigated the effect of nutrition care provided by primary
      health professionals on adult patients' dietary behaviours. METHODS: The
      systematic review included all studies published between January 2000 and January
      2015 that involved nutrition care by one or more primary health professionals to
      adult patients and incorporated at least one quantified food-related outcome
      measure (e.g. daily intake of vegetables in grams, weekly servings of lean
      meats). After data extraction, the methodological quality of each study was
      appraised using the Mixed Methods Appraisal Tool. RESULTS: Twenty-one studies,
      totalling 12497 participants were included. The design, intensity, theoretical
      underpinning and follow-up period of interventions were diverse. Twelve studies
      found significant improvements in participants' dietary behaviours, such as
      increased daily consumption of fruit, vegetables, high-fibre bread and fish.
      However, seven studies did not identify any improvement in dietary behaviours;
      one observed equal improvements among participants in the intervention and
      control groups and one found a reduction in participants' daily fruit and
      vegetable intake. CONCLUSION: Interventions involving nutrition care provided by
      primary health professionals have the potential to improve patients' dietary
      behaviours. However, the consistency and clinical significance of intervention
      outcomes are unclear. Further consideration of factors that may influence the
      effectiveness of interventions, but not traditionally measured, are required.

PMID- 26289045
TI  - Declining functional connectivity and changing hub locations in Alzheimer's
      disease: an EEG study.
AB  - BACKGROUND: EEG studies have shown that patients with Alzheimer's disease (AD)
      have weaker functional connectivity than controls, especially in higher frequency
      bands. Furthermore, active regions seem more prone to AD pathology. How
      functional connectivity is affected in AD subgroups of disease severity and how
      network hubs (highly connected brain areas) change is not known. We compared AD
      patients with different disease severity and controls in terms of functional
      connections, hub strength and hub location. METHODS: We studied routine 21
      channel resting-state electroencephalography (EEG) of 318 AD patients (divided
      into tertiles based on disease severity: mild, moderate and severe AD) and 133
      age-matched controls. Functional connectivity between EEG channels was estimated
      with the Phase Lag Index (PLI). From the PLI-based connectivity matrix, the
      minimum spanning tree (MST) was derived. For each node (EEG channel) in the MST,
      the betweenness centrality (BC) was computed, a measure to quantify the relative
      importance of a node within the network. Then we derived color-coded head plots
      based on BC values and calculated the center of mass (the exact middle had x and
      y values of 0). A shifting of the hub locations was defined as a shift of the
      center of mass on the y-axis across groups. Multivariate general linear models
      with PLI or BC values as dependent variables and the groups as continuous
      variables were used in the five conventional frequency bands. RESULTS: We found
      that functional connectivity decreases with increasing disease severity in the
      alpha band. All, except for posterior, regions showed increasing BC values with
      increasing disease severity. The center of mass shifted from posterior to more
      anterior regions with increasing disease severity in the higher frequency bands,
      indicating a loss of relative functional importance of the posterior brain
      regions. CONCLUSIONS: In conclusion, we observed decreasing functional
      connectivity in the posterior regions, together with a shifted hub location from
      posterior to central regions with increasing AD severity. Relative hub strength
      decreases in posterior regions while other regions show a relative rise with
      increasing AD severity, which is in accordance with the activity-dependent
      degeneration theory. Our results indicate that hubs are disproportionally
      affected in AD.

PMID- 26289047
TI  - Tradeoff between robustness and elaboration in carotenoid networks produces
      cycles of avian color diversification.
AB  - BACKGROUND: Resolution of the link between micro- and macroevolution calls for
      comparing both processes on the same deterministic landscape, such as genomic,
      metabolic or fitness networks. We apply this perspective to the evolution of
      carotenoid pigmentation that produces spectacular diversity in avian colors and
      show that basic structural properties of the underlying carotenoid metabolic
      network are reflected in global patterns of elaboration and diversification in
      color displays. Birds color themselves by consuming and metabolizing several
      dietary carotenoids from the environment. Such fundamental dependency on the most
      upstream external compounds should intrinsically constrain sustained evolutionary
      elongation of multi-step metabolic pathways needed for color elaboration unless
      the metabolic network gains robustness - the ability to synthesize the same
      carotenoid from an additional dietary starting point. RESULTS: We found that
      gains and losses of metabolic robustness were associated with evolutionary cycles
      of elaboration and stasis in expressed carotenoids in birds. Lack of metabolic
      robustness constrained lineage's metabolic explorations to the immediate
      biochemical vicinity of their ecologically distinct dietary carotenoids, whereas
      gains of robustness repeatedly resulted in sustained elongation of metabolic
      pathways on evolutionary time scales and corresponding color elaboration.
      CONCLUSIONS: The structural link between length and robustness in metabolic
      pathways may explain periodic convergence of phylogenetically distant and
      ecologically distinct species in expressed carotenoid pigmentation; account for
      stasis in carotenoid colors in some ecological lineages; and show how the
      connectivity of the underlying metabolic network provides a mechanistic link
      between microevolutionary elaboration and macroevolutionary diversification.

PMID- 26289048
TI  - Does the direction of tumescent solution delivery matter in endovenous laser
      ablation of the great saphenous vein?
AB  - BACKGROUND: The aim of this study was to compare the two different directions of
      tumescent solution delivery (from distal to proximal knee to the saphenofemoral
      junction [SFJ] or proximal to distal SFJ to the knee) in terms of differences in
      tumescent volume, number of punctures, and pain and comfort scores of patients.
      METHODS: A total of 100 patients were treated with endovenous laser ablation
      (EVLA) under local anesthesia between August 2013 and October 2013. These 100
      patients were divided into two groups. In group 1, tumescent solution was
      delivered in a proximal to distal direction. In group 2, the tumescent solution
      was delivered in a distal to proximal direction. In each group, the great
      saphenous vein (GSV) diameter, delivered total energy, treated GSV length,
      delivered tumescent volume, number of punctures, and pain and comfort scores were
      recorded for each patient. RESULTS: All patients were treated unilaterally. EVLA
      was performed with 100% technical success in all patients. There was no
      difference statistically between group 1 and group 2 according to GSV diameter,
      delivered total energy, and treated GSV length. Average tumescent volume, number
      of punctures, and pain scores in group 2 were lower than in group 1 (p = 0.0001;
      p < 0.05). Also, the average comfort score was higher in group 2 than in group 1
      (p = 0.0001; p < 0.05). CONCLUSIONS: We believe that delivering the tumescent
      solution in a distal to proximal direction increases the comfort of both patient
      and surgeon with lower tumescent volume during the EVLA of the GSV.

PMID- 26289051
TI  - A doctor who chose an assisted death.

PMID- 26289049
TI  - Evaluation of a disease specific rheumatoid arthritis self-management education
      program, a single group repeated measures study.
AB  - BACKGROUND: Rheumatoid Arthritis is a progressive and disabling disease,
      predicted to increase in prevalence over the next 50 years. Self-management is
      acknowledged as an integral part in the management of chronic disease. The
      rheumatoid arthritis specific self-management program delivered by health
      professionals was developed by Arthritis Western Australia in 2006. The purpose
      of this study was to determine whether this program would achieve early benefits
      in health related outcomes, and whether these improvements would be maintained
      for 12 months. METHODS: Individuals with rheumatoid arthritis were referred from
      rheumatologists. Participants with co-existing inflammatory musculoskeletal
      conditions were excluded. All participants completed a 6-week program.
      Assessments occurred at baseline (8 weeks prior to intervention), pre
      intervention, post-intervention, and 6 and 12 month follow ups. Outcomes measured
      included pain and fatigue (numerical rating scale, 0-10), depression and anxiety
      (hospital anxiety and depression questionnaire), health distress, and quality of
      life (SF-36 version 2). RESULTS: There were significant improvements in mean [SD]
      fatigue (5.7 [2.4] to 5.1 [2.6]), depression (6.3 [4.3] to 5.6 [3.9]) and SF-36
      mental health (44.5 [11.1] to 46.5 [9.5]) immediately following intervention,
      with long term benefits for depression (6.3 [4.3] to 4.9 [3.9]), and SF-36
      subscales mental health (44.5 [11.1] to 47.8 [10.9]), role emotional (41.5 [13.2]
      to 46.5 [11.8]), role physical (35.0 [11.0] to 40.2 [12.1]) and physical function
      (34.8 [11.5] to 38.6 [10.7]). CONCLUSION: Participants in the program recorded
      significant improvements in depression and mental health post-intervention, which
      were maintained to 12 months follow up.

PMID- 26289050
TI  - The role of a hepatitis C virus vaccine: modelling the benefits alongside direct
      acting antiviral treatments.
AB  - BACKGROUND: Hepatitis C virus (HCV) elimination is being seriously considered
      globally. Current elimination models require a combination of highly effective
      HCV treatment and harm reduction, but high treatment costs make such strategies
      prohibitively expensive. Vaccines should play a key role in elimination but their
      best use alongside treatments is unclear. For three vaccines with different
      efficacies we used a mathematical model to estimate the additional reduction in
      HCV prevalence when vaccinating after treatment; and to identify in which
      settings vaccines could most effectively reduce the number of treatments required
      to achieve fixed reductions in HCV prevalence among people who inject drugs
      (PWID). METHODS: A deterministic model of HCV transmission among PWID was
      calibrated for settings with 25, 50 and 75% chronic HCV prevalence among PWID,
      stratified by high-risk or low-risk PWID. For vaccines with 30, 60 or 90%
      efficacies, different rates of treatment and vaccination were introduced. We
      compared prevalence reductions achieved by vaccinating after treatment to prevent
      reinfection and vaccinating independently of treatment history in the community;
      and by allocating treatments and vaccinations to specific risk groups and
      proportionally across risk groups. RESULTS: Vaccinating after treatment was
      minimally different to vaccinating independently of treatment history, and
      allocating treatments and vaccinations to specific risk groups was minimally
      different to allocating them proportionally across risk groups. Vaccines with 30
      or 60% efficacy provided greater additional prevalence reduction per vaccination
      in a setting with 75% chronic HCV prevalence among PWID than a 90% efficacious
      vaccine in settings with 25 or 50% chronic HCV prevalence among PWID.
      CONCLUSIONS: Vaccinating after treatment is an effective and practical method of
      administration. In settings with high chronic HCV prevalence among PWID, even
      modest coverage with a low-efficacy vaccine could provide significant additional
      prevalence reduction beyond treatment alone, and would likely reduce the cost of
      achieving prevalence reduction targets.

PMID- 26289052
TI  - HLA-B27 and psoriatic disease: a modern view of an old relationship.
AB  - Psoriasis and PsA are the main phenotypes of psoriatic disease. Both conditions
      are highly polygenic diseases in which stochastic and environmental factors are
      crucial in the pathogenic process. Although the MHC region is a highly dense
      genetic area, most of the genetic basis of psoriatic disease within it resides in
      the HLA region. For decades, HLA-C*06 has been accepted as the main descriptor of
      the two main phenotypes of skin psoriasis. There is now compelling evidence to
      suggest that HLA-C*06 is only a genetic biomarker for skin involvement and not
      for joint involvement in psoriatic disease. The role of HLA-B*27 in the genetic
      aetiology of PsA has been recognized since the 1970s. Recent population case
      control studies with adequate patient groups and replication cohorts, as well as
      confirmation studies in family pedigrees through the use of modern molecular
      typing methods, have reinforced the aetiological role of this allele in PsA.
      These studies have offered a new vision of the role of this allele in disease
      expression. This review contextualizes the latest findings on the role of HLA-B27
      in psoriatic disease, emphasizing those aspects of particular interest for
      clinical practice. 

PMID- 26289053
TI  - Low Serum Level of Klotho Is an Early Predictor of Atherosclerosis.
AB  - The Klotho gene, identified as an 'aging suppressor' gene, encodes a single-pass
      transmembrane protein. The extracellular domain of Klotho is cleaved and released
      in the blood stream, where it may function as a vasculoprotective hormone.
      Carotid artery intima-media thickness (CIMT), flow-mediated dilation (FMD) of the
      brachial artery and epicardial fat thickness (EFT) have been reported as early
      predictors of atherosclerosis. We aimed to investigate the relationship between
      serum Klotho levels and early atherosclerotic predictors, including EFT, FMD and
      CIMT in healthy adults. Fifty healthy volunteers were enrolled in this study,
      consisting of 21 males and 29 females with median age of 32 years. They were free
      of known risk factors for cardiovascular diseases. Serum Klotho levels were
      determined by the ELISA method. The study population was divided into two groups
      (n = 25 for each) according to the median serum Klotho level (459.4 pg/mL):
      higher Klotho (HK) group (613.6 pg/mL; ranges of 501.2-772.6 pg/mL) and lower
      Klotho (LK) group (338.7 pg/mL; ranges of 278.8-430.3 pg/mL). EFT was measured by
      transthoracic echocardiography, and CIMT and FMD were measured with standard
      procedures. The LK group showed lower values of FMD (p = 0.012) and larger values
      of EFT (p = 0.01) and CIMT (p < 0.001), compared to the HK group. Thus, the low
      serum Klotho levels were associated with increased EFT and CIMT and with the
      decreased FMD in the study population. We propose that the lower serum Klotho
      level is a newly identified predictor of atherosclerosis. 

PMID- 26289054
TI  - Validation of the Spanish Version of the Face Name Associative Memory Exam (S
      FNAME) in Cognitively Normal Older Individuals.
AB  - The Face Name Associative Memory Exam (FNAME) is a paired associative memory test
      that has demonstrated sensitivity to amyloid burden in cognitively normal
      individuals, a biomarker of preclinical Alzheimer's disease. Normative data
      adjusted for age were reported in American healthy individuals older than 57. We
      aimed to report the psychometric characteristics of a Spanish version of FNAME (S
      FNAME) when administered to Spanish-speaking people. We sought to investigate
      convergent validity of S-FNAME with another memory measure and to identify which
      demographic characteristics might be associated with performance on S-FNAME. We
      administered the S-FNAME to 110 literate, cognitively normal, Spanish individuals
      older than 49 years from the Memory Clinic Fundacio ACE. Construct validity of S
      FNAME showed 2 components: face-name and face-occupation. A significant
      correlation between S-FNAME and Word List from the WMS-III supported convergent
      validity. The S-FNAME was also associated with age and gender. Thus, we provide
      normative data for age and gender.

PMID- 26289055
TI  - Regression-Based Normative Formulae for the Repeatable Battery for the Assessment
      of Neuropsychological Status for Older Adults.
AB  - The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
      has become a popular cognitive screening instrument, particularly in elderly
      patients. Prior studies presented lookup tables for RBANS normative data based on
      age, gender, education, and race using a group of 718 community-dwelling older
      adults. However, regression-based normative formulae that simultaneously correct
      for all demographic variables may be more sensitive for detecting late life
      cognitive decline. Using data from the prior studies, linear regression was used
      to generate such formulae in the Indexes and subtests of the RBANS. Results
      indicated that ~11% of the variance of Index scores was accounted for by these
      demographic variables, and 13% of variance in subtest scores. Although some
      differences were present between the lookup and regression-based norms, it is
      expected that these current results will present more accurate demographic
      corrections that allow clinicians and researchers to better interpret individual
      performances on the RBANS.

PMID- 26289056
TI  - Hypermethylation of ZNF545 is associated with poor prognosis in patients with
      early-stage hepatocellular carcinoma after thermal ablation.

PMID- 26289057
TI  - Intestinal intussusception in a young women: unusual cause and specific
      management.
AB  - BACKGROUND: Intussusception in adults is a rare cause of abdominal pain that is
      often associated with organic pathology. We describe a case of ileocolic
      intussusception revealing a cecal adenocarcinoma in a young woman successfully
      managed by laparoscopic-assisted surgery adhering to oncological principles. CASE
      PRESENTATION: A 30-year-old woman with a family history of colon adenocarcinoma
      in a young brother presented to our emergency department with a 2-month history
      of intermittent colicky abdominal pain accompanied by nausea and vomiting.
      Physical examination showed a palpable mass in the right lower quadrant of the
      abdomen. Computed tomography showed a 3-layered structure giving the
      characteristic target-shaped appearance in the ascending colon, highly suggestive
      for an ileocolic intussusception associated with right colic parietal thickening
      and an adjacent lymphadenopathy. Patient was planned for laparoscopic exploration
      and eventually definitive surgery. Intra-operatively, we found an ileocolic
      intussusception with thickening of the colic wall and slight proximal intestinal
      dilation. Multiple lymphadenopathies along the ileocecal artery were observed.
      Laparoscopic right hemicolectomy was performed following strict oncologic
      principles with "en bloc resection" and lymphadenectomy given the risk of an
      underlying malignancy. Considering this risk, previous reduction of the
      invaginated segments was not attempted and primary extracorporeal anastomosis was
      performed using manual sutures. Macroscopic examination of the resected specimen
      revealed a tumor mass of the caecal wall .The histological analysis identified a
      moderately differentiated tubular adenocarcinoma invading the serosa (T3) without
      permeation of the lymphatic or venous capillaries. No lymphatic metastasis of 28
      nodes removed was seen. Postoperative course was uneventful and patient was
      discharged 5 days after surgery. Postoperative chest, abdomen, and pelvis CT scan
      were normal. Therefore, tumor is classified as stage II A (T3N0 M0).There was
      loss of MLH2 and MSH6 protein expression on immunohistochemistry findings
      reflecting a microsatellite instability phenotype, and the patient was followed
      up without adjuvant chemotherapy. CONCLUSION: Ileocolic intussusception rarely
      revealed a cancer in young adults. Laparoscopic surgery has a special interest in
      the diagnosis and treatment in this pathology. Oncogenetic consultation should be
      required in malignant lesion.

PMID- 26289058
TI  - The Impact of a Prenatal Education Video on Rates of Breastfeeding Initiation and
      Exclusivity during the Newborn Hospital Stay in a Low-income Population.
AB  - BACKGROUND: Guidelines recommend prenatal education to improve breastfeeding
      rates; however, effective educational interventions targeted at low-income,
      minority populations are needed as they remain less likely to breastfeed.
      OBJECTIVE: To determine whether a low-cost prenatal education video improves
      hospital rates of breastfeeding initiation and exclusivity in a low-income
      population. METHODS: A total of 522 low-income women were randomized during a
      prenatal care visit occurring in the third trimester to view an educational video
      on either breastfeeding or prenatal nutrition and exercise. Using multivariable
      analyses, breastfeeding initiation rates and exclusivity during the hospital stay
      were compared. RESULTS: Exposure to the intervention did not affect breastfeeding
      initiation rates or duration during the hospital stay. The lack of an effect on
      breastfeeding initiation persisted even after controlling for partner, parent, or
      other living at home and infant complications (adjusted odds ratio [OR] = 1.05,
      95% CI, 0.70-1.56). In addition, breastfeeding exclusivity rates during the
      hospital stay did not differ between the groups (P = .87). CONCLUSION: This study
      suggests that an educational breastfeeding video alone is ineffective in
      improving the hospital breastfeeding practices of low-income women. Increasing
      breastfeeding rates in this at-risk population likely requires a multipronged
      effort begun early in pregnancy or preconception.

PMID- 26289060
TI  - Drastic change in density of states upon martensitic phase transition for
      metamagnetic shape memory alloy Ni2Mn(1+x)In(1-x).
AB  - We have unravelled the electronic structure of a class of metamagnetic shape
      memory alloy Ni2Mn1+x In1-x by combining bulk-sensitive hard x-ray photoelectron
      spectroscopy and first-principles density-functional calculations. A sharp drop
      in the Ni 3d e(g) density of states forming a pseudogap in the martensitic phase
      transition (MPT) for x   =   0.36 has been observed near the Fermi level. As a
      feature of MPT, hysteretic behaviour of this drop has been confirmed in both
      cooling and warming. This pseudogap is responsible for the giant negative
      magnetoresistance. The experimental result is well reproduced by the first
      principle calculation. We have also clarified theoretically that the MPT is
      linked to a competition of ferromagnetic and anti-ferromagnetic coupling between
      ordinary and anti-site Mn atoms.

PMID- 26289059
TI  - Exclusive Breastfeeding Experiences among Mexican American Women.
AB  - BACKGROUND: According to the Centers for Disease Control and Prevention, Hispanic
      breastfeeding mothers begin early formula supplementation at higher rates than
      other ethnic groups, which can lead to shorter breastfeeding duration and
      decreased exclusive breastfeeding. Acculturation, the process of adopting beliefs
      and behaviors of another culture, appears to influence breastfeeding practices of
      Hispanic women in the United States. Little is known about Mexican American
      mothers' formula use and exclusive breastfeeding within the context of
      acculturation. OBJECTIVE: Our study identified perceived benefits and barriers to
      exclusive breastfeeding and levels of acculturation among Mexican American women
      living in a Midwestern city. METHODS: We used a qualitative descriptive design
      integrating Pender's Health Promotion Model concepts. Individual interviews were
      conducted in English or Spanish (N = 21). The revised Acculturation Rating Scale
      for Mexican Americans was used to examine acculturation levels. RESULTS:
      Acculturation scores indicated that the majority (66%) of the sample was "very
      Mexican oriented." Most women exclusively breastfed, with a few using early
      supplementation for "insufficient milk production." Three themes emerged: (1) It
      is natural that a woman give life and also provide the best food for her baby;
      (2) Breastfeeding is ultimately a woman's decision but is influenced by
      tradition, guidance, and encouragement; and (3) Breast milk is superior but life
      circumstances can challenge one's ability to breastfeed. CONCLUSION: Strong
      familial/cultural traditions supported and normalized breastfeeding. Barriers to
      exclusive breastfeeding were similar to breastfeeding women in general, in the
      United States. Findings support the need for culturally competent and
      individualized lactation care.

PMID- 26289061
TI  - Recent advances in paediatric respiratory medicine.
AB  - This review highlights important advances in paediatric respiratory medicine
      since 2014, excluding cystic fibrosis. It focuses mainly on the more common
      conditions, bronchopulmonary dysplasia, bronchiolitis and preschool wheezing,
      asthma, pneumonia and sleep, and highlights some of the rarer conditions such as
      primary ciliary dyskinesia and interstitial lung disease (ILD). 

PMID- 26289062
TI  - Thalassaemia in children: from quality of care to quality of life.
AB  - Over the past few decades, there has been a remarkable improvement in the
      survival of patients with thalassaemia in developed countries. Availability of
      safe blood transfusions, effective and accessible iron chelating medications, the
      introduction of new and non-invasive methods of tissue iron assessment and other
      advances in multidisciplinary care of thalassaemia patients have all contributed
      to better outcomes. This, however, may not be true for patients who are born in
      countries where the resources are limited. Unfortunately, transfusion-transmitted
      infections are still major concerns in these countries where paradoxically
      thalassaemia is most common. Moreover, oral iron chelators and MRI for monitoring
      of iron status may not be widely accessible or affordable, which may result in
      poor compliance and suboptimal iron chelation. All of these limitations will lead
      to reduced survival and increased thalassaemia-related complications and
      subsequently will affect the patient's quality of life. In countries with limited
      resources, together with improvement of clinical care, strategies to control the
      disease burden, such as public education, screening programmes and appropriate
      counselling, should be put in place. Much can be done to improve the situation by
      developing partnerships between developed countries and those with limited
      resources. Future research should also particularly focus on patient's quality of
      life as an important outcome of care. 

PMID- 26289063
TI  - Steroid-sensitive nephrotic syndrome: an evidence-based update of
      immunosuppressive treatment in children.
AB  - Nephrotic syndrome is one of the most common paediatric glomerular diseases, with
      an incidence of around two per 100,000 children per year. Corticosteroids are the
      mainstay of treatment, with 85%-90% of children going into remission with an 8
      week course of treatment. Unfortunately, nephrotic syndrome follows a relapsing
      and remitting course in the majority, with 90% relapsing at least once. About
      half will progress to frequently relapsing nephrotic syndrome (FRNS) or steroid
      dependent nephrotic syndrome (SDNS). Different initial steroid regimens have been
      evaluated since the first trials in Europe and America in the 1960s. Most trials
      have been designed to evaluate the optimal duration of the initial therapy,
      rather than different cumulative doses of corticosteroid, or the management of
      relapses. Until recently, these data suggested that an initial treatment duration
      of up to 6 months reduced the number of children developing a relapse, without
      evidence of increased steroid toxicity. Recently, three large, well-designed
      randomised control trials were published, which demonstrated no significant
      reduction in risk of relapse or of developing FRNS by extended treatment compared
      with 2 or 3 months. While there are few trial data to guide the treatment of
      individual relapses in steroid-sensitive nephrotic syndrome (SSNS), there is some
      evidence that a short course of corticosteroid therapy during upper respiratory
      tract infection may prevent relapse. In patients with FRNS or SDNS who continue
      to relapse despite low-dose alternate-day steroids a number of non
      corticosteroid, steroid-sparing immunosuppressive agents (cyclophosphamide,
      ciclosporin, tacrolimus, mycophenolate mofetil, levamisole, rituximab) have been
      shown to reduce the risk of relapse and of FRNS. However, there are limited head
      to-head data to inform which agent should be preferred. In this article, we
      review recent data from randomised trials to update paediatricians on the current
      evidence supporting interventions in SSNS.

PMID- 26289064
TI  - A retrospective analysis of paediatric tuberculosis diagnosis in London: room for
      improvement?

PMID- 26289065
TI  - Risk of MRSA Infection in Patients with Intermittent versus Persistent MRSA Nares
      Colonization.
AB  - OBJECTIVE: To determine the relative risk of invasive methicillin-resistant
      Staphylococcus aureus (MRSA) infection among non-colonized (NC) patients,
      intermittently colonized (IC) patients, and persistently colonized (PC) patients.
      DESIGN: Observational cohort study of patient data collected longitudinally over
      a 41-month period. SETTING: Department of Veterans Affairs Eastern Colorado
      Healthcare System, a tertiary care medical center. PATIENTS: Any patient who
      received >=5 MRSA nasal swab tests between February 20, 2010, and July 26, 2013.
      In total, 3,872 patients met these criteria, 0 were excluded, 95% were male, 71%
      were white, and the mean age was 62.9 years on the date of study entry. METHODS:
      Patients were divided into cohorts based on MRSA colonization status. Physicians
      reviewed medical records to identify invasive infection and were blinded to
      colonization status. Cox and Kaplan-Meier analyses were used to assess the
      relationship between colonization status and invasive infection. RESULTS: In
      total, 102 patients developed invasive MRSA infections, 16.3% of these were PC
      patients, 11.2% of these were IC patients, and 0.5% of these were NC patients. PC
      patients were at higher risk of invasive infection than NC patients (hazard ratio
      [HR] 36.8; 95% CI, 18.4-73.6; P<.001). IC patients were also at higher risk than
      NC patients (HR, 22.8; 95% CI, 13.3-39.3; P<.001). The difference in risk between
      PC and IC patients was not statistically significant (HR, 1.61; 95% CI, 0.94
      2.78, P=.084). Alternate analysis methods confirmed these results. CONCLUSIONS:
      The risk of invasive MRSA infection is much higher among PC and IC patients,
      supporting routine clinical testing for colonization. However, this risk is
      similar among PC and IC patients, suggesting that distinguishing between the 2
      colonization states may not be clinically important.

PMID- 26289066
TI  - Trends in the access to and the use of antipsychotic medications and psychotropic
      co-treatments in Asian patients with schizophrenia.
AB  - To date, antipsychotics remain the mainstay of treatment for schizophrenia and
      related disorders although other psychotropic medications and non-pharmaceutical
      interventions have been used adjunctively in some patients and settings. Regular
      surveys on access to and prescription patterns of psychotropic medications in
      clinical practice are an important and efficient way of examining the use and
      time trends of treatments in a given population and region. Unlike developed
      Western countries, Asian countries have not fully undergone
      deinstitutionalisation of the severely and chronically mentally ill, and
      community-based mental health services are still under-developed. As a result, a
      large number of psychiatric patients still receive treatments in psychiatric
      hospitals. Moreover, there have been very limited studies examining access to and
      prescription patterns of psychotropic medications for schizophrenia patients in
      Asian countries. In this paper, we focus on the only international project on the
      use of psychotropic medications in schizophrenia patients in selected East and
      Southeast Asian countries/territories summarising its major findings. Most of the
      first- and second-generation antipsychotics (FGAs and SGAs) are available in
      Asian countries, but the access to psychotropic medications is largely affected
      by socio-cultural and historical contexts, health insurance schemes, health care
      policy, medication cost and consumers' preference across different
      countries/territories. Overall, the proportional use of FGAs, high dose
      antipsychotic treatment and antipsychotic polypharmacy have decreased, while the
      use of SGAs and antidepressants have increased and the utilisation of
      benzodiazepines and mood stabilisers has remained relatively stable over time.
      However, within these general trends, there is great inter-country variation
      regarding the psychotropic prescribing patterns and trends in Asian schizophrenia
      patients that also seems to differ from data in many Western countries. 

PMID- 26289067
TI  - Myeloid Cells and Related Chronic Inflammatory Factors as Novel Predictive
      Markers in Melanoma Treatment with Ipilimumab.
AB  - PURPOSE: Immunotherapy with ipilimumab improves the survival of patients with
      metastatic melanoma. Because only around 20% of patients experience long-term
      benefit, reliable markers are needed to predict a clinical response. Therefore,
      we sought to determine if some myeloid cells and related inflammatory mediators
      could serve as predictive factors for the patients' response to ipilimumab.
      EXPERIMENTAL DESIGN: We performed an analysis of myeloid cells in the peripheral
      blood of 59 stage IV melanoma patients before the treatment and at different time
      points upon the therapy using a clinical laboratory analysis and multicolor flow
      cytometry. In addition, the production of related inflammatory factors was
      evaluated by ELISA or Bio-Plex assays. RESULTS: An early increase in eosinophil
      count during the treatment with ipilimumab was associated with an improved
      clinical response. In contrast, elevated amounts of monocytic myeloid-derived
      suppressor cells (moMDSC), neutrophils, and monocytes were found in nonresponders
      (n = 36) as compared with basal levels and with responding patients (n = 23).
      Moreover, in nonresponders, moMDSCs produced significantly more nitric oxide, and
      granulocytic MDSCs expressed higher levels of PD-L1 than these parameters at
      baseline and in responders, suggesting their enhanced immunosuppressive capacity.
      Upon the first ipilimumab infusion, nonresponders displayed elevated serum
      concentrations of S100A8/A9 and HMGB1 that attract and activate MDSCs.
      CONCLUSIONS: These findings highlight additional mechanisms of ipilimumab effects
      and suggest levels of eosinophils, MDSCs, as well as related inflammatory factors
      S100A8/A9 and HMGB1 as novel complex predictive markers for patients who may
      benefit from the ipilimumab therapy. Clin Cancer Res; 21(24); 5453-9. (c)2015
      AACR.

PMID- 26289068
TI  - Cabozantinib Inhibits Abiraterone's Upregulation of IGFIR Phosphorylation and
      Enhances Its Anti-Prostate Cancer Activity.
AB  - PURPOSE: Abiraterone improves the overall survival of men with metastatic
      castration-resistant prostate cancer. However, de novo or adaptive resistance to
      abiraterone limits its activity. Rational combinations of drugs with different
      mechanisms of action that overcome resistance mechanisms may improve the efficacy
      of therapy. To that end, we studied the molecular and phenotypic effects of the
      combination of cabozantinib plus abiraterone. EXPERIMENTAL DESIGN: Three prostate
      cancer cell lines were used to interrogate the in vitro molecular and
      antiproliferative effects of the single agents and combination of cabozantinib
      and abiraterone. The in vivo impact of the combination was assessed using the
      LAPC4-CR xenograft mouse model. RESULTS: In vitro proliferation studies
      demonstrated single-agent doses between 2 MUmol/L and 10 MUmol/L for abiraterone
      and cabozantinib inhibit prostate cancer cell proliferation in a dose-dependent
      manner, and the anticancer activity of abiraterone is enhanced when combined with
      cabozantinib. In vivo LAPC4-CR xenograft mouse studies also showed that
      cabozantinib can improve the antitumor activity of abiraterone. Cabozantinib, a
      multiple receptor tyrosine kinase inhibitor, enhances the ability of abiraterone
      to inhibit AR activity in a cell line-dependent manner. In addition, our cell
      line studies demonstrate abiraterone-stimulated insulin-like growth factor I
      receptor (IGFIR) phosphorylation with downstream activation of MEK1/2 and ERK1/2,
      and that this potential adaptive resistance mechanism was inhibited by
      cabozantinib. CONCLUSIONS: Cabozantinib can enhance the efficacy of abiraterone
      by blocking multiple compensatory survival mechanisms, including IGFIR
      activation, and supports the assessment of the combination in a clinical trial.

PMID- 26289069
TI  - Absolute Effect of Prostate Cancer Screening: Balance of Benefits and Harms by
      Center within the European Randomized Study of Prostate Cancer Screening.
AB  - PURPOSE: The balance of benefits and harms in prostate cancer screening has not
      been sufficiently characterized. We related indicators of mortality reduction and
      overdetection by center within the European Randomized Study of Prostate Cancer
      Screening (ERSPC). EXPERIMENTAL DESIGN: We analyzed the absolute mortality
      reduction expressed as number needed to invite (NNI = 1/absolute risk reduction;
      indicating how many men had to be randomized to screening arm to avert a prostate
      cancer death) for screening and the absolute excess of prostate cancer detection
      as number needed for overdetection (NNO = 1/absolute excess incidence; indicating
      the number of men invited per additional prostate cancer case), and compared
      their relationship across the seven ERSPC centers. RESULTS: Both absolute
      mortality reduction (NNI) and absolute overdetection (NNO) varied widely between
      the centers: NNI, 200-7,000 and NNO, 16-69. Extent of overdiagnosis and mortality
      reduction was closely associated [correlation coefficient, r = 0.76; weighted
      linear regression coefficient, beta = 33; 95% confidence interval (CI), 5-62;
      R(2) = 0.72]. For an averted prostate cancer death at 13 years of follow-up, 12
      to 36 excess cases had to be detected in various centers. CONCLUSIONS: The
      differences between the ERSPC centers likely reflect variations in prostate
      cancer incidence and mortality, as well as in screening protocol and performance.
      The strong interrelation between the benefits and harms suggests that efforts to
      maximize the mortality effect are bound to increase overdiagnosis and might be
      improved by focusing on high-risk populations. The optimal balance between
      screening intensity and risk of overdiagnosis remains unclear.

PMID- 26289070
TI  - Preclinical Efficacy of Ron Kinase Inhibitors Alone and in Combination with PI3K
      Inhibitors for Treatment of sfRon-Expressing Breast Cancer Patient-Derived
      Xenografts.
AB  - PURPOSE: Recent studies have demonstrated that short-form Ron (sfRon) kinase
      drives breast tumor progression and metastasis through robust activation of the
      PI3K pathway. We reasoned that upfront, concurrent inhibition of sfRon and PI3K
      might enhance the antitumor effects of Ron kinase inhibitor therapy while also
      preventing potential therapeutic resistance to tyrosine kinase inhibitors (TKI).
      EXPERIMENTAL DESIGN: We used patient-derived breast tumor xenografts (PDX) as
      high-fidelity preclinical models to determine the efficacy of single-agent or
      dual Ron/PI3K inhibition. We tested the Ron kinase inhibitor ASLAN002 with and
      without coadministration of the PI3K inhibitor NVP-BKM120 in hormone receptor
      positive [estrogen receptor (ER)(+)/progesterone receptor (PR)(+)] breast PDXs
      with and without PIK3CA gene mutation. RESULTS: Breast PDX tumors harboring wild
      type PIK3CA showed a robust response to ASLAN002 as a single agent. In contrast,
      PDX tumors harboring mutated PIK3CA demonstrated partial resistance to ASLAN002,
      which was overcome with addition of NVP-BKM120 to the treatment regimen. We
      further demonstrated that concurrent inhibition of sfRon and PI3K in breast PDX
      tumors with wild-type PIK3CA provided durable tumor stasis after therapy
      cessation, whereas discontinuation of either monotherapy facilitated tumor
      recurrence. CONCLUSIONS: Our work provides preclinical rationale for targeting
      sfRon in patients with breast cancer, with the important stipulation that tumors
      harboring PIK3CA mutations may be partially resistant to Ron inhibitor therapy.
      Our data also indicate that tumors with wild-type PIK3CA are most effectively
      treated with an upfront combination of Ron and PI3K inhibitors for the most
      durable response. Clin Cancer Res; 21(24); 5588-600. (c)2015 AACR.

PMID- 26289071
TI  - Comparative analysis of thermoplastic masks versus vacuum cushions in
      stereotactic body radiotherapy.
AB  - BACKGROUND: To compare thermoplastic masks (TMP) and vacuum cushion system (VCS)
      to assess differences in interfraction set up accuracy in patients treated with
      stereotactic radiotherapy (SBRT) for oligometastatic lung cancer. Secondarily, to
      survey radiotherapy technologists to assess their satisfaction with the two
      systems. METHODS: Retrospective study of patients treated with lung SBRT between
      2008 to 2012 at our institution. Immobilization was performed for 73 treatment
      sessions (VCS = 40; TMP = 33). A total of 246 cone-beams were analysed. Patients
      considered ineligible for surgery with a life expectancy >=6 months and
      performance status > 1 were included. Target lesion location was verified by cone
      beam computed tomography (CBCT) prior to each session, with displacements
      assessed by CBCT simulation prior to each treatment session. Couch shifts were
      registered prospectively in vertical, longitudinal, and latero-lateral directions
      to obtain Kernel coordinates (3D representation). Technologists were surveyed to
      assess their satisfaction with indexing, positioning, and learning curve of the
      two systems. Setup displacements were obtained in all patients for each treatment
      plan and for each session. To assess differences between the immobilization
      systems, a t-test (Welch) was performed. RESULTS: Mean displacements for the TMP
      and VC systems, respectively, were as follows: session one, 0.64 cm vs 1.05 cm (p
      = 0.0002); session two, 0.49 cm vs 1.02 cm (p < 0.0001), and session three, 0.56
      vs 0.97 cm (p = 0.0011). TMP resulted in significantly smaller shifts vs. VCS in
      all three treatment sessions. Technologists rated the learning curve, set up, and
      positioning more highly for TMP versus VCS. CONCLUSIONS: Due to the high doses
      and steep gradients in lung SBRT, accurate and reproducible inter-fraction set up
      is essential. We found that thermoplastic masks offers better reproducibility
      with significantly less interfractional set up displacement than vacuum cushions.
      Moreover, radiotherapy technologists rated the TMP system higher. Taken together,
      these two findings suggest that TMP may be preferable to VCS. However, more
      research is needed to determine both inter- and intrafraction error to identify
      the optimal immobilisation system for use in lung SBRT.

PMID- 26289072
TI  - Reliable scaling of position weight matrices for binding strength comparisons
      between transcription factors.
AB  - BACKGROUND: Scoring DNA sequences against Position Weight Matrices (PWMs) is a
      widely adopted method to identify putative transcription factor binding sites.
      While common bioinformatics tools produce scores that can reflect the binding
      strength between a specific transcription factor and the DNA, these scores are
      not directly comparable between different transcription factors. Other methods,
      including p-value associated approaches (Touzet H, Varre J-S. Efficient and
      accurate p-value computation for position weight matrices. Algorithms Mol Biol.
      2007;2(1510.1186):1748-7188), provide more rigorous ways to identify potential
      binding sites, but their results are difficult to interpret in terms of binding
      energy, which is essential for the modeling of transcription factor binding
      dynamics and enhancer activities. RESULTS: Here, we provide two different ways to
      find the scaling parameter lambda that allows us to infer binding energy from a
      PWM score. The first approach uses a PWM and background genomic sequence as input
      to estimate lambda for a specific transcription factor, which we applied to show
      that lambda distributions for different transcription factor families correspond
      with their DNA binding properties. Our second method can reliably convert lambda
      between different PWMs of the same transcription factor, which allows us to
      directly compare PWMs that were generated by different approaches. CONCLUSION:
      These two approaches provide computationally efficient ways to scale PWM scores
      and estimate the strength of transcription factor binding sites in quantitative
      studies of binding dynamics. Their results are consistent with each other and
      previous reports in most of cases.

PMID- 26289073
TI  - Efficacy of a half-grip technique using a fine tip LigaSureTM, Dolphin Tip
      Sealer/Divider, on liver dissection in swine model.
AB  - BACKGROUND: Recently, a lot of energy devices in the surgical field, especially
      in the liver surgery, have been developed, and a fine tip LigaSureTM, Dolphin Tip
      Sealer/Divider (DT-SD) also has been used frequently to dissect liver parenchyma
      as well as ultrasonically activated device (USAD). However, the utility of this
      instrument for liver dissection (LD) is still unknown. Moreover, to reduce
      bleeding during LD, a half-grip technique (HGT) was contrived. We herein report
      an experimental study in swine model to evaluate the feasibility and
      effectiveness of HGT using DT-SD for LD. METHODS: The swine model experiment was
      carried out under general anesthesia by veterinarians. LD was performed
      repeatedly by DT-SD with the HGT (Group A, n = 6), or the conventional clamp
      crush technique (CCT) (Group B, n = 6), and by variable mode USAD (Group C, n =
      6). The dissection length and depth (cm) as well as bleeding volume (g) were
      measured carefully, and the dissection area (cm(2)) and speed (cm(2)/min) were
      calculated precisely. Histological examinations of the dissection surfaces were
      also executed. Mann-Whitney's U test was used for Statistical analyses with
      variance at a significance level of 0.05. RESULTS: Among the three groups, the
      three averages of dissection lengths were unexpectedly equalized to 8.3 cm. The
      dissection area (cm(2)) was 9.9 +/- 5.1 in Group A, 9.8 +/- 4.7 in Group B, and
      9.9 +/- 4.5 in Group C. The mean blood loss during LD was 10.6 +/- 14.8 g in
      Group A, 41.4 +/- 39.2 g in Group B, and 34.3 +/- 39.2 g in Group C. For Group A,
      the bleeding rate was the least, 0.9 +/- 1.0 g/cm(2), and the average depth of
      coagulation was the thickest, 1.47 +/- 0.29 mm, among the three groups (p <
      0.05). The dissection speed in Group A (1.3 +/- 0.3 cm(2)/min) was slower, than
      that in Group C (p < 0.05). CONCLUSIONS: This report indicates firstly that the
      HGT using DT-SD bring the least blood loss when compared with CCT or USAD.
      Although the HGT is feasible and useful for LD, to popularize the HGT, further
      clinical studies will be needed.

PMID- 26289074
TI  - Identification of a novel linear epitope on the NS1 protein of avian influenza
      virus.
AB  - BACKGROUND: The NS1 protein of avian influenza virus (AIV) is an important
      virulent factor of AIV. It has been shown to counteract host type I interferon
      response, to mediate host cell apoptosis, and to regulate the process of protein
      synthesis. The identification of AIV epitopes on NS1 protein is important for
      understanding influenza virus pathogenesis. RESULTS: In this paper, we describe
      the generation, identification, and epitope mapping of a NS1 protein-specific
      monoclonal antibody (MAb) D9. First, to induce the production of MAbs, BALB/c
      mice were immunized with a purified recombinant NS1 expressed in E. coli. The
      spleen cells from the immunized mice were fused with myeloma cells SP2/0, and
      through screening via indirect ELISAs, a MAb, named D9, was identified. Western
      blot assay results showed that MAb D9 reacted strongly with the recombinant NS1.
      Confocal laser scanning microscopy showed that this MAb also reacts with NS1
      expressed in 293T cells that had been transfected with eukaryotic recombinant
      plasmids. Results from screening a phage display random 7-mer peptide library
      with MAb D9 demonstrated that it recognizes phages displaying peptides with the
      consensus peptide WNLNTV--VS, which closely matches the (182)WNDNTVRVS(190) of
      AIV NS1. Further identification of the displayed epitope was performed with a set
      of truncated polypeptides expressed as glutathione S-transferase fusion proteins,
      and the motif (182)WNDNT(186) was defined as the minimal unit of the linear B
      cell epitope recognized by MAb D9 in western blot assays. Moreover, homology
      analysis showed that this epitope is a conserved motif among AIV. CONCLUSIONS: We
      identified a conserved linear epitope, WNDNT, on the AIV NS1 protein that is
      recognized by MAb D9. This MAb and its epitope may facilitate future studies on
      NS1 function and aid the development of new diagnostic methods for AIV detection.

PMID- 26289075
TI  - Neuropathological comparisons of amnestic and nonamnestic mild cognitive
      impairment.
AB  - BACKGROUND: Although there are studies investigating the pathologic origins of
      mild cognitive impairment (MCI), they have revolved around comparisons to normal
      elderly individuals or those with Alzheimer's disease (AD) or other dementias.
      There are few studies directly comparing the comprehensive neuropathology of
      amnestic (aMCI) and nonamnestic (naMCI) MCI. METHODS: The database of the Brain
      and Body Donation Program ( www.brainandbodydonationprogram.org ), a longitudinal
      clinicopathological study of normal aging and neurodegenerative disorders, was
      queried for subjects who were carrying a diagnosis of aMCI or naMCI at the time
      of autopsy. Neuropathological lesions, including neuritic plaques,
      neurofibrillary tangles (NFTs), Lewy bodies (LBs), infarcts, cerebral white
      matter rarefaction (CWMR), cerebral amyloid angiopathy (CAA), and concurrent
      major clinicopathological diagnoses, including Parkinson's disease (PD) were
      analyzed. RESULTS: Thirty four subjects with aMCI and 15 naMCI met study
      criteria. Subjects with aMCI were older at death (88 vs. 83 years of age, p =
      0.03). Individuals with naMCI had higher densities of LBs within the temporal
      lobe (p = 0.04) while subjects with aMCI had a propensity for increased NFTs in
      parietal and temporal lobes (p values = 0.07). After adjusting for age at death,
      the only significant difference was greater densities of temporal lobe NFTs
      within the aMCI group. Other regional pathology scores for plaques, NFTs, and LBs
      were similar between groups. Subjects met clinico-pathological criteria for co
      existent PD in 24 % aMCI and 47 % naMCI while neuropathological criteria for AD
      were met in equal percentages of aMCI and of naMCI cases (53 %); these
      proportional differences were not significant (p values > 0.35). Furthermore,
      regardless of amnestic status, there was a greater presence of CAA (71 % of MCI
      with executive dysfunction vs. 39 % without p = 0.03) and a greater presence of
      CWMR (81 % of MCI with executive dysfunction and 54 % without p = 0.046) in MCI
      cases with executive dysfunction. CONCLUSIONS: No single pathologic entity
      strongly dichotomized MCI groups, perhaps due to the pathologic heterogeneity
      found within both entities. However, these data suggest the possibility for naMCI
      to have a propensity for increased LBs and aMCI for increased NFTs in select
      anatomic regions.

PMID- 26289076
TI  - Evaluation of dose reduction versus standard dosing for maintenance of remission
      in patients with spondyloarthritis and clinical remission with anti-TNF (REDES
      TNF): study protocol for a randomized controlled trial.
AB  - BACKGROUND: Dose reduction schedules of tumor necrosis factor antagonists (anti
      TNF) as maintenance therapy in patients with spondyloarthritis are used
      empirically in clinical practice, despite the lack of clinical trials providing
      evidence for this practice. METHODS/DESIGN: To address this issue the Spanish
      Society of Rheumatology (SER) and Spanish Society of Clinical Pharmacology (SEFC)
      designed a 3-year multicenter, randomized, open-label, controlled clinical trial
      (2 years for inclusion and 1 year of follow-up). The study is expected to include
      190 patients with axial spondyloarthritis on stable maintenance treatment (>=4
      months) with any anti-TNF agent at doses recommended in the summary of product
      characteristics. Patients will be randomized to either a dose reduction arm or
      maintenance of the dosing regimen as per the official labelling recommendations.
      Randomization will be stratified according to the anti-TNF agent received before
      study inclusion. Patient follow-up, visit schedule, and examinations will be
      maintained as per normal clinical practice recommendations according to SER
      guidelines. The study aims to test the hypothesis of noninferiority of the dose
      reduction strategy compared with standard treatment. The first patients were
      recruited in July 2012, and study completion is scheduled for the end of April
      2015. DISCUSSION: The REDES-TNF study is a pragmatic clinical trial that aims to
      provide evidence to support a medical decision now made empirically. The study
      results may help inform clinical decisions relevant to both patients and
      healthcare decision makers. TRIAL REGISTRATION: EudraCT 2011-005871-18 (21
      December 2011).

PMID- 26289077
TI  - Influence of pelvic incidence-lumbar lordosis mismatch on surgical outcomes of
      short-segment transforaminal lumbar interbody fusion.
AB  - BACKGROUND: The importance of pelvic incidence-lumbar lordosis (PI-LL: PI minus
      LL) mismatch is emphasized in long-segment fusion for adult spinal deformity;
      however, there are few studies evaluating the influence of PI-LL on surgical
      outcomes after short-segment fusion. In this study, we have examined the effects
      of PI-LL mismatch on surgical outcomes of short-segment lumbar intervertebral
      fusion for lumbar degenerative diseases. METHODS: Patients with lumbar
      degenerative disease treated by short-segment (1 or 2 levels) transforaminal
      lumbar interbody fusion were divided into Group A (PI-LL <= 10 degrees : n = 22)
      and Group B (PI-LL >= 11 degrees : n = 30). Pre-and post-operative patient
      symptoms were assessed by the visual analogue scale (VAS: scores 0-100 mm; for
      LBP, lower-extremity pain, and lower-extremity numbness), a detailed VAS for LBP
      while in motion, standing, and sitting, and the Oswestry disability index (ODI).
      Surgical outcomes were evaluated by the Nakai score (3 = excellent to 0 = poor.
      Post-operative data were acquired for at least one year following surgery and
      were compared between the two groups. Multiple regression analyses were used to
      evaluate the relative influence of PI-LL on each pre-and post-operative parameter
      (VAS, detailed VAS and ODI) adjusted for age, sex, fusion levels, body mass
      index, presence of scoliosis, diabetes mellitus and depression. RESULTS: The
      surgical outcomes in Group A were significantly better than those of Group B.
      Group A showed better post-operative VAS scores for LBP, particularly LBP while
      standing (11.9 vs. 25.8). The results of the multivariate analyses showed no
      significant correlation between PI-LL and pre-operative symptoms, but did show a
      significant correlation between PI-LL and the post-operative VAS score for LBP,
      lower extremity pain, and numbness. CONCLUSIONS: This study is the first to find
      that PI-LL mismatch influences post-operative residual symptoms, such as LBP,
      lower extremity pain and numbness. Among the three types of LBP examined in the
      detailed VAS, LBP while standing was most strongly related to PI-LL mismatch. The
      importance of maintaining spinopelvic alignment is emphasized, particularly when
      treating patients with adult spinal deformity using long-segment fusion surgery.
      However, our results indicate that surgeons should pay attention to sagittal
      spinopelvic alignment and avoid post-operative PI-LL mismatch even when treating
      patients with short-segment lumbar interbody fusion.

PMID- 26289079
TI  - Relationships Among Rheological, Sensory Texture, and Swallowing Pressure
      Measurements of Hydrocolloid-Thickened Fluids.
AB  - The objective of this study was to examine the relationships among three
      categories of measurements (rheological, sensory texture, and swallowing
      pressure) from fluids thickened to two different viscosities with 15 different
      hydrocolloids. Fluids at viscosities of 300 and 1500 cP (at 30 s(-1)) were
      targeted because these are the viscosities corresponding to the barium standards
      used in radiographic dysphagia diagnosis. Within the low viscosity (nectar)
      fluids (300 cP), the sensory properties thickness, stickiness, adhesiveness,
      mouth coating, and number of swallows were highly positively correlated with each
      other and highly positively correlated with the flow behavior index, n value (an
      indicator of shear-thinning behavior). Within the higher viscosity (thin honey)
      fluids (1500 cP), the sensory textures of adhesiveness, stickiness, mouth
      coating, and number of swallows correlated positively with rheological measures
      of n value. Swallowing pressures measured in the anterior oral cavity correlated
      negatively with the consistency coefficient k [shear stress/(shear rate) (n) ].
      Samples that were more shear thinning (lower n values, higher k values) were
      generally perceived as less thick, with less adhesive properties (stickiness,
      adhesiveness, mouthcoating, and number of swallows). This information can be
      useful for selecting thickeners for people with dysphagia. A desirable thickener
      for many dysphagic patients would be one that allowed for a safe swallow by being
      viscous enough to reduce airway penetration, yet pleasant to drink, having the
      minimal perceived thickness and mouthcoating associated with greater shear
      thinning. 

PMID- 26289080
TI  - Right bundle branch and hypothyroidism in an elderly woman: a complex interaction
      in the risk of syncope.

PMID- 26289078
TI  - Regulation effect of Aspirin Eugenol Ester on blood lipids in Wistar rats with
      hyperlipidemia.
AB  - BACKGROUND: Aspirin eugenol ester (AEE) is a promising drug candidate for
      treatment of inflammation, pain and fever and prevention of cardiovascular
      diseases with less side effects. The experiment will be conducted to investigate
      the efficacy of AEE on curing hyperlipidemia in Wistar rats. The rats were fed
      with high fat diet (HFD) for 8 weeks to induce hyperlipidemia. RESULTS: Compared
      with the model group, the results showed that AEE at 54 mg/kg dosage could
      significantly decrease the hyperlipidemia indexes including triglyceride (TG),
      low density lipoprotein (LDL) and total cholesterol (TCH) (p < 0.01), increase
      high density lipoprotein (HDL) (p < 0.05) for five weeks drug administration.
      Meanwhile, simvastatin had same effect on hyperlipidemia indexes such as TG, LDL,
      TC, but no significant increase in HDL. CONCLUSION: AEE was effective against
      hyperlipidemia and had better anti-hyperlipidemic effect than its component,
      acetylsalicylic acid (Aspirin, ASA), eugenol and integration of ASA and eugenol.
      Under the experimental circumstance, the optimal dose of AEE to cure
      hyperlipidemia is 54 mg/kg for five weeks in Wistar rats.

PMID- 26289081
TI  - Clinicopathologic Comparison of Urothelial Bladder Carcinoma in Young and Elder
      Patients.
AB  - Bladder cancer (BC) is a common aggressive malignancy and Urothelial bladder
      cancer (UBC) consists of the majority of BC. There is uncertainty regarding the
      clinicopathologic characteristics of UBCs in younger patients. To investigate the
      clinicopathologic features of young patients with UBCs. A total of 2825
      pathological records of UBC patients, including 42 young patients (<= 30 years
      old) and 2783 elder patients (> 30 years old), were retrospectively studied. The
      stage distribution classified was statistically significant (Chi (2) = 12.25, P =
      0.02) between young and old patients; superficial tumors was far more in young
      patients than in old patients. More young patients tended to be low- and moderate
      grade UBCs (Chi (2) = 6.75, P = 0.009). Young patients with superficial UBCs also
      showed lower recurrence rate, compared to elder patients (Chi (2) = 5.77, P =
      0.02). For 5-year survival rate, young patients (93.8%) showed better than elder
      patients (85.1%) (Chi (2) = 4.01, P = 0.045). Patients younger than 30 years old
      with UBCs had low-grade and low-stage tumors and exhibited better prognosis than
      elder patients.

PMID- 26289082
TI  - The Parent-Version of the Spence Children's Anxiety Scale (SCAS-P) in Chinese and
      Italian Community Samples: Validation and Cross-Cultural Comparison.
AB  - The current study aimed to validate the parent-version of the Spence Children's
      Anxiety Scale (SCAS-P) among Chinese and Italian community adolescents and to
      compare adolescents' anxiety symptoms in these two countries. Chinese (N = 456)
      and Italian (N = 452) adolescents and their parents participated in the study.
      Results showed that: (1) the six correlated-factor structure was demonstrated and
      invariant across countries. (2) The reliability of the total scale was good in
      both samples, whereas reliabilities of subscales were acceptable and moderate in
      Chinese and Italian samples, respectively. (3) The SCAS-P showed good convergent
      and divergent validity. (4) Adolescent-parent agreement was from low to medium
      while mother-father agreement ranged from medium to high. (5) There were cultural
      and gender differences in levels of parent-report anxiety symptoms. In
      conclusion, SCAS-P seems to be a promising parent-report instrument to assess
      Chinese and Italian adolescents' anxiety symptoms. 

PMID- 26289083
TI  - High-Risk Atherosclerotic Cardiovascular Disease in a Real-World Employed
      Japanese Population: Prevalence, Cardiovascular Event Rates, and Costs.
AB  - AIM: To assess the prevalence of high-risk atherosclerotic cardiovascular disease
      (ASCVD, defined as history of acute coronary syndrome [hACS], cerebrovascular
      atherosclerotic disease [CeVAD], peripheral artery disease [PAD], or coronary
      artery disease w/diabetes [CADD]) and associated costs and cardiovascular (CV)
      events in Japan. METHODS: A retrospective analysis was conducted using the Japan
      Medical Data Center (JMDC) database (2006-2011). ASCVD prevalence was estimated
      on the basis of diagnoses for CeVAD, PAD, CADD, and hACS (ACS claim > 30-<= 365
      days after ACS-related hospitalization) during 1/1/ 2008-12/31/2009. Population
      denominators used in the prevalence estimations were provided by JMDC. A
      subcohort with an insurance coverage for >= 12 months before and >= 24 months
      after first/index ASCVD claim during 1/1/2008-12/31/2009 were analyzed on the
      basis of costs (in 2012 US dollars) and events. RESULTS: ASCVD prevalence was
      1,869/100,000 population. In total, 8,112 patients met inclusion criteria for the
      cost and CV event analyses. Among these patients, 4.0% experienced any event
      (myocardial infarction, stroke, coronary revascularization, hospitalization for
      unstable angina) in the year after ASCVD diagnosis, which decreased to 2.2% in
      year 2. First-year event rates were highest (22%) in patients with hACS. Mean
      [SD] all-cause costs per patient in year 1 were $7,031 [$14,359] for all patients
      with ASCVD combined. Extrapolated to the entire employed population, total first
      year costs were estimated at $8.2 billion. CONCLUSIONS: ASCVD is not rare in
      Japan, even within a relatively young population of employed persons. Further,
      the total direct first-year cost burden of ASCVD in the employed Japanese
      population is high. These data may inform future economic assessments of new
      ASCVD treatments.

PMID- 26289084
TI  - CXCL16 in Vascular Pathology Research: from Macro Effects to microRNAs.
AB  - Chemokines and their receptors have become significant factors in atherosclerosis
      research. CXCL16 is a multifunctional agent located on a separate locus to all
      other known chemokines and binds only to its "unique" receptor named CXCR6. As a
      scavenger receptor, adhesion molecule, and chemokine, it quickly became an
      interesting target in atherosclerosis research as all its functions have a role
      in vascular pathology. The investigation of the role of CXCL16 in
      atherosclerosis, although shown in in vitro studies, animal knockout models, and
      CXCL16 gene polymorphisms, haplotypes, and circulating levels, still shows
      puzzling results. Genetic and epigenetic studies have just scratched the surface
      of research necessary for a better assessment of the significance and perspective
      of this marker in plaque development and progression. In this review, we will
      summarize current knowledge about CXCL16 in atherosclerosis. Additionally, we
      will point out the importance of bioinformatics tools for the detection of
      potentially new CXCL16 regulatory networks through microRNA activity. This review
      aims to provide a better understanding of the underlying mechanisms, define more
      specific biomarkers, and discover new therapeutic targets. 

PMID- 26289086
TI  - 5th European Conference on Schizophrenia Research: bridging gaps-improving
      outcomes : 24-26 September 2015, Berlin, Germany.

PMID- 26289085
TI  - High-Density Lipoprotein Subfractions and Their Oxidized Subfraction Particles in
      Patients with Chronic Kidney Disease.
AB  - AIM: Chronic kidney disease (CKD) may lead to reduced concentrations of high
      density lipoprotein (HDL) and its subfractions (HDL2 and HDL3), and damage them
      via inflammation and oxidative stress. The present study aimed to determine the
      contribution of such changes to cardiovascular disease (CVD) in patients with
      CKD. METHODS: The levels of total cholesterol, low-density lipoprotein
      cholesterol, HDL-C, HDL2, HDL3, apolipoproteins, malondialdehyde-modified LDL
      (MDA-LDL), oxidized (ox) HDL, oxHDL2, and oxHDL3 were measured in blood samples
      from patients with CKD (stages 2-5, n=86) who were not on dialysis and from
      patients undergoing hemodialysis (CKD stage 5D, n=25). The patients were followed
      up for 28+/-9 months after baseline examinations and CVD events were recorded.
      RESULT: The levels of HDL3 and ApoA1 in HDL3 fraction decreased according to CKD
      severity, whereas those of HDL2 and ApoA1 in HDL2 fraction did not differ. The
      levels of oxHDL were similar across CKD stages. The levels of oxHDL3 and MDA-LDL
      were decreased, whereas those of oxHDL2 increased according to CKD severity.
      Multivariate analyses using the Cox proportional hazards model selected high
      levels of oxHDL and its subfractions, and those adjusted with HDL-C and HDL
      subfractions or ApoA1 in HDL fractions respectively, compared with HDL-C and HDL
      subfractions or ApoA1 in HDL fractions alone as independent risk factors for CVD
      events. CONCLUSION: The levels of HDL subfractions and their oxidized subfraction
      particles differed among patients with CKD. The increasing levels of oxHDL
      subfractions might cause a high frequency of CVD events in such patients.

PMID- 26289087
TI  - An Assessment of the Consumption of Energy and Selected Minerals and Their
      Content in the Hair of Children Aged 1-4 Years.
AB  - The aim of this study was to assess the consumption of energy and selected
      minerals (Ca, Mg, Fe, Zn, Cu) and their content in the hair of children aged 1-4
      years. Seventy-five children were divided into three age subgroups: 12-24-month
      olds, 25-36-month-olds and 37-48-month-olds. The data on energy intake and
      consumption of nutrients were obtained by means of a nutritional interview. The
      content of elements in the hair was measured by means of flame atomic absorption
      spectrometry (AAS) with an AAS-3 spectrophotometer (Zeiss). The daily food
      rations of children aged 12-36 months were characterised by adequate energy
      value, but the values of Ca and K were too low, whereas the content of Mg, Zn and
      Cu was high. On the other hand, the daily food rations of children aged 37-48
      months provided sufficient amounts of Mg and Zn, but the value of Cu was too
      high, whereas energy, Ca, K and Fe were too low. About 42.7% of the children
      under study were characterised by an abnormal state of nutrition. An inadequately
      balanced diet needs to be corrected by educating parents or guardians in
      appropriate nutrition. There are significant correlations (r > 0.9) between the
      supply of Ca in the diet of children aged 1-4 years and the content of this
      element in their hair.

PMID- 26289088
TI  - Clinicopathological characteristics of patients with immunoglobulin A nephropathy
      showing acute exacerbations after favorable long-term clinical courses.
AB  - BACKGROUND: Sometimes, acute and progressive proteinuria increases occur in
      patients with IgA nephropathy (IgAN) after favorable long-term clinical courses
      of >10 years, but their clinical and histological characteristics are not well
      understood. METHODS: We retrospectively selected 20 IgAN patients who had been
      followed for >10 years after their initial biopsies ((1st)Bx) and underwent
      second biopsies ((2nd)Bx), because their proteinuria increased to >1 g/day. Eight
      patients with acute exacerbations (Group A) showed acute proteinuria increases
      after long periods of mild proteinuria. Their clinicopathological characteristics
      were analyzed as a case series and were compared with those in Group B that
      comprised 12 patients with persistent proteinuria. RESULTS: Group A experienced
      acute proteinuria increases and significant hematuria increases compared with the
      -1-year (P = 0.006) and -3-year (P = 0.010) time points before the (2nd)Bx, which
      contrasted to the clinical course in Group B. In Group A, glomerulosclerosis (GS)
      and the arteriosclerosis score did not differ between the (2nd)Bx and the
      (1st)Bx, and most patients (88 %) showed cellular and/or fibrocellular crescents
      within the (2nd)Bx. Compared with Group B, the (2nd)Bx revealed that the
      percentage of cellular and/or fibrocellular crescents (P = 0.001) was
      significantly higher, whereas the percentage of GS (P = 0.012) and the
      arteriosclerosis score (P = 0.020) were significantly lower in Group A.
      CONCLUSION: Rapid proteinuria and hematuria increases, and acute histological
      lesions characterize acute exacerbations in IgAN after favorable long-term
      clinical courses.

PMID- 26289089
TI  - Detrimental effects of niacin/laropiprant on microvascular reactivity and red
      cell deformability in patients with elevated lipoprotein(a) levels.
AB  - Several studies have found a beneficial effect of nicotinic acid on lipid
      profile, but there remains a limitation in the clinical use of nicotinic acid due
      to its side effects. In this study, 46 (F/M = 22/24, age = 58.74 +/- 10.02 years)
      patients with Lp(a) >=500 mg/L and with a previous arterial thrombotic event were
      treated with nicotinic acid/laropiprant (Tredaptive(r)). We found a significant
      reduction in the Lp(a) values at T1 (after 12 months), with a decrease of 32.3 %
      from baseline levels. At T1, 11 patients (23.9 %) showed Lp(a) levels to be <500
      mg/L. PAT values were significantly decreased after treatment (2.13 +/- 0.81 vs
      1.74 +/- 0.42, p = 0.001), showing a worsening of endothelial function in 27
      (58.6 %) patients. A significantly higher number of patients had RHI <1.5 after
      the treatment [18 (39.1 %) vs 8 (17.4 %)]. Blood rheology worsened as ED was
      impaired (p < 0.0001) after 12 months, whereas WHV, plasma viscosity, and red
      cell aggregation did not show any significant differences in comparison to
      baseline. Patients with a worsening in microvascular reactivity in comparison to
      baseline showed a marked impairment in ED (0.3327 +/- 0.037 vs 0.3091 +/- 0.0351;
      p < 0.0001), while others showed only a mild, even though significant, reduction
      (0.3347 +/- 0.0299 vs 0.3272 +/- 0.0235; p = 0.044). In the light of the results
      of HPS2-THRIVE study, we may hypothesize that the addition of laropiprant to
      niacin might be responsible for these negative effects. In turn, these effects
      might explain, at least in part, the lack of a clinical net benefit of
      niacin/laropiprant in the trial.

PMID- 26289090
TI  - Human natural killer cells: news in the therapy of solid tumors and high-risk
      leukemias.
AB  - It is well established that natural killer (NK) cells play an important role in
      the immunity against cancer, while the involvement of other recently identified,
      NK-related innate lymphoid cells is still poorly defined. In the haploidentical
      hematopoietic stem cell transplantation for the therapy of high-risk leukemias,
      NK cells have been shown to exert a key role in killing leukemic blasts residual
      after conditioning. While the clinical results in the cure of leukemias are
      excellent, the exploitation of NK cells in the therapy of solid tumors is still
      limited and unsatisfactory. In solid tumors, NK cell function may be inhibited
      via different mechanisms, occurring primarily at the tumor site. The cellular
      interactions in the tumor microenvironment involve tumor cells, stromal cells and
      resident or recruited leukocytes and may favor tumor evasion from the host's
      defenses. In this context, a number of cytokines, growth factors and enzymes
      synthesized by tumor cells, stromal cells, suppressive/regulatory myeloid and
      lymphoid cells may substantially impair the function of different tumor-reactive
      effector cells, including NK cells. The identification and characterization of
      such mechanisms may offer clues for the development of new immunotherapeutic
      strategies to restore effective anti-tumor responses. In order to harness NK cell
      based immunotherapies, several approaches have been proposed, including
      reinforcement of NK cell cytotoxicity by means of specific cytokines, antibodies
      or drugs. These new tools may improve NK cell function and/or increase tumor
      susceptibility to NK-mediated killing. Hence, the integration of NK-based
      immunotherapies with conventional anti-tumor therapies may increase chances of
      successful cancer treatment. 

PMID- 26289091
TI  - Dysfunction of PSA-specific CD8+ T cells in prostate cancer patients correlates
      with CD38 and Tim-3 expression.
AB  - The efficacy of immunotherapy in cancer patients is influenced by differences in
      their immune status. An evaluation of immunocompetence before therapy may help to
      predict therapeutic success and guide the selection of appropriate regimens. We
      assessed the preexisting cellular immunity against prostate-specific antigen
      (PSA) in untreated prostate cancer patients and healthy controls through
      measurement of the phenotype and function of CD8(+) T cells. Our data show that
      the majority of healthy men possess functional PSA-specific CD8(+) T cells in
      contrast to cancer patients, where <50 % showed a CD8(+) T cell response. PSA146
      154-specific CD8(+) T cells of these patients had a higher expression of the
      activation marker CD38 and the exhaustion marker Tim-3, indicating that PSA
      specific cells are exhausted. The heterogeneity of the CD8(+) T cell response
      against PSA in prostate cancer patients may influence their response to therapy
      and is a factor to be taken into account while designing and selecting treatment
      regimens.

PMID- 26289092
TI  - External fixator for treatment of the sub-acute and chronic multi-ligament
      injured knee.
AB  - PURPOSE: To assess whether the use of an articulated external fixator provides
      improvements in the mobility, stability and subjective function of patients
      undergoing ligament reconstruction. METHODS: Thirty-three patients with sub-acute
      and chronic knee dislocation were subjected to multi-ligament reconstruction
      surgery. These patients were randomly allocated to two groups for immobilization
      after reconstruction: group 0-control (18 patients), with rigid knee bracing, and
      group 1-articulated external fixator (15 patients). The stability of the
      reconstructed ligaments was assessed after at least 14 months (26.6-month
      average) postoperatively by physical examination. Deficit of extension and
      flexion was measured in relation to the unaffected contralateral knee, and the
      Lysholm knee scoring scale questionnaire was applied. RESULTS: There was no
      difference in the assessment of joint stability between the groups. In group 1,
      patients showed less flexion deficit (4.8 degrees  +/- 5.4 degrees  vs. 18.2
      degrees  +/- 14.8 degrees , p < 0.05), and the percentage of patients with a
      flexion deficit of 5 degrees  or less were higher compared with group 0 (64 vs.
      18 %, p < 0.05). There was no difference between groups in relation to extension
      loss. Group 1 also presented better Lysholm scores, with 73 % of patients rated
      as excellent or good compared with 35 % in group 0 (p < 0.05). CONCLUSIONS:
      Compared with the control rehabilitation protocol with rigid knee bracing in
      extension, the use of an articulated external fixator in the treatment of chronic
      multi-ligament-injured knees provided the same ligament stability, better final
      range of motion and improved Lysholm score. Patients presenting with chronic
      multi-ligament instability should be considered for articulated external fixation
      to supplement reconstruction procedures. LEVEL OF EVIDENCE: Randomized controlled
      trial, Level I.

PMID- 26289093
TI  - Association between NCF4 rs4821544T/C polymorphism and inflammatory bowel disease
      risk in Caucasian: a meta-analysis.
AB  - OBJECTIVE: Published studies on the association between NCF4 rs4821544T/C
      polymorphism and inflammatory bowel disease (IBD) risk in Caucasian have yielded
      conflicting results. The present study aimed to provide more reliable conclusions
      by conducting a meta-analysis. METHODS: All eligible studies were extracted from
      Wiley Online Library, Chinese National Knowledge Infrastructure and PubMed
      databases. Odds ratios (ORs) with 95 % confidence intervals (CIs) were used to
      assess the associations between rs4821544T/C polymorphism and IBD risk in
      Caucasian. RESULTS: A total of 13 case-control studies comprising 7441 Crohn's
      disease (CD) patients, 2565 ulcerative colitis (UC) patients and 8315 controls
      were included in this meta-analysis. Significant associations were found between
      CD and the rs4821544T/C polymorphism in three genetic models (C vs T: OR = 1.11,
      95 % CI: 1.06, 1.16, P = 0.000; CC vs TT: OR = 1.31, 95 % CI: 1.18, 1.45, P =
      0.000; CC/TC vs TT: OR = 1.07, 95 % CI: 1.01, 1.13, P = 0.014; CC vs TC/TT: OR =
      1.28, 95 % CI: 1.16, 1.42, P = 0.000). However, significant associations were not
      found in UC under any genetic models (C vs T: OR = 1.04, 95 % CI: 0.97, 1.11, P =
      0.264; CC vs TT: OR = 1.10, 95 % CI: 0.93, 1.30, P = 0.284; TC vs TT: OR = 1.04,
      95 % CI: 0.95, 1.13, P = 0.429; CC/TC vs TT: OR = 1.04, 95 % CI: 0.95, 1.13, P =
      0.390; CC vs TC/TT: OR = 1.07, 95 % CI: 0.91, 1.26, P = 0.409). CONCLUSION: This
      meta-analysis suggested that the rs4821544T/C polymorphism was associated with
      CD, but not UC in Caucasian.

PMID- 26289094
TI  - Association between Val66Met polymorphisms in brain-derived neurotrophic factor
      gene and asthma risk: a meta-analysis.
AB  - OBJECTIVE: The Val66Met polymorphisms in brain-derived neurotrophic factor (BDNF)
      gene have been reported to be associated with asthma risk, while the results are
      inconclusive. Considering a single study may lack the power to provide reliable
      conclusion, we performed a meta-analysis to investigate the association between
      the Val66Met polymorphisms and asthma susceptibility. METHODS: A comprehensive
      literature search of PubMed, Embase, China National Knowledge Infrastructure
      (CNKI) and Wanfang databases was conducted before February 12, 2015. The pooled
      odds ratio (OR) with 95 % confidence intervals (CIs) were calculated. RESULTS:
      Six eligible studies with a total of 3501 subjects were finally included in this
      meta-analysis. Overall, a significantly increased risk was detected in the
      Val66Met G allele (G vs. A: OR 1.33, 95 % CI 1.19-1.49, P = 5.61E-07; GG vs. GA +
      AA: OR 1.48, 95 % CI 1.20-1.83, P = 3.14E-04; GG vs. GA: OR 1.48, 95 % CI 1.17
      1.89, P = 0.001; GG vs. AA: OR 1.62, 95 % CI 1.20-2.19, P = 0.002). Moreover,
      stratification by ethnicity indicated marked association between the Val66Met G
      allele and asthma risk in Caucasians (G vs. A: OR 1.29, 95 % CI 1.12-1.49, P =
      0.001; GG + GA vs. AA: OR 1.59, 95 % CI 1.03-2.46, P = 0.039; GG vs. GA + AA: OR
      1.32, 95 % CI 1.11-1.57, P = 0.001; GG vs. GA: OR 1.28, 95 % CI 1.07-1.53, P =
      0.007; GG vs. AA: OR 1.72, 95 % CI 1.11-2.68, P = 0.015). CONCLUSION: Our present
      meta-analysis suggests that the Val66Met polymorphisms in BDNF gene are
      potentially associated with asthma risk in Caucasians. Further well-designed case
      control studies with larger sample size and more ethnic groups are needed to
      confirm these conclusions.

PMID- 26289096
TI  - Superconductivity in 3R-Ta(1-x)M(x)Se2 (M = W, Mo).
AB  - The 3-layer rhombohedral (3R) polytype of TaSe2-x Te x is known to display a
      superconducting transition temperature that is between 6 and 17 times higher than
      that of the two-layer hexagonal (2H) polytype. The remarkable difference in T c,
      although clearly associated with a difference in polytype, could have been due to
      an electronic effect specific to the Te-Se substitution. Here we report that
      small amounts of Mo or W doping lead to a 2H to 3R polytype transition in Ta1-x
      Mo x Se2 and Ta1-x W x Se2. The 3R polytype materials are again found to have
      substantially higher T c (~2 K for Ta0.9W0.1Se2 and Ta0.9Mo0.1Se2) than the 2H
      material (0.15 K), eliminating the possibility that any special characteristics
      of the Te/Se substitution are responsible for the dramatic difference in T c. We
      infer that a three-layer stacking sequence is strongly preferred for
      superconductivity over a two-layer stacking sequence in the TaSe2 system. 

PMID- 26289095
TI  - Exploratory analysis of candidate germline gene polymorphisms in breast cancer
      patients treated with neoadjuvant anthracycline-containing chemotherapy and
      associations with febrile neutropenia.
AB  - AIM: SNPs may be associated with (side) effects of chemotherapy and may be useful
      as biomarkers to predict febrile neutropenia. PATIENTS & METHODS: 187 DNA samples
      extracted from formalin-fixed paraffin-embedded tissue from patients with stage
      II/III HER2-negative breast cancer were genotyped. RESULTS: Candidate SNPs were
      selected and explored for association with febrile neutropenia and/or
      pathological complete response. TT genotype of 388 C>T in FGFR4 (rs351855) had a
      tendency toward higher incidence of febrile neutropenia during neoadjuvant
      chemotherapy, compared with the CT (p = 0.383) genotype and compared with the CC
      genotype (p = 0.068). CONCLUSION: The TT genotype of 388 C>T FGFR4 may be related
      to incidence of febrile neutropenia during neoadjuvant TAC (docetaxel,
      doxorubicin, cyclophosphamide) chemotherapy and is possibly useful as a patient
      related risk factor when assessing febrile neutropenia risk. Original submitted
      23 January 2015; Revision submitted 26 May 2015.

PMID- 26289097
TI  - Insights into the UDP-sugar selectivities of human UDP-glycosyltransferases
      (UGT): a molecular modeling perspective.
AB  - Enzymes of the human uridine diphosphate (UDP)-glycosyltransferase (UGT)
      superfamily typically catalyze the covalent addition of a sugar from UDP-sugar
      cofactors to relatively small lipophilic compounds. The sugar conjugates are
      often biologically less active with improved water-solubility, facilitating more
      effective elimination from the body. Experimental data indicate that UGT proteins
      exhibit differing selectivities toward various UDP-sugars. Although, three
      dimensional (3D) structures of UGT proteins are required to provide insights into
      the UDP-sugar selectivities observed for the various UGT proteins, there are
      currently, no experimental structures available for human UGTs bound to UDP
      sugar(s). Thus, the absence of 3D structures poses a major challenge for
      analyzing UDP-sugar selectivity at an atomic level. In this commentary, we
      highlight the application of comparative homology modeling for understanding the
      UDP-sugar selectivities of UGT proteins. Homology models of the C-terminal (CT)
      domain indicate a highly conserved structural fold across the UGT family with
      backbone root mean-squared deviations (rmsds) between 0.066 and 0.079 A with
      respect to the UGT2B7-CT X-ray crystal structure. The models show that four
      residues in the terminal portion of the CT signature sequence play an important
      role in UDP-sugar selectivity. The N-terminal domain is less likely to be
      associated with UDP-sugar selectivity, although, a conserved residue, Arg-259
      (UGT2B7 numbering) in the UGT 1 and 2 families may influence UDP-sugar
      selectivity. Overall, the models demonstrate excellent agreement with
      experimental observations in predicting the key residues that influence the
      selectivity of UDP-sugar binding.

PMID- 26289098
TI  - Xenobiotic-metabolizing enzymes in plants and their role in uptake and
      biotransformation of veterinary drugs in the environment.
AB  - Many various xenobiotics permanently enter plants and represent potential danger
      for their organism. For that reason, plants have evolved extremely sophisticated
      detoxification systems including a battery of xenobiotic-metabolizing enzymes.
      Some of them are similar to those in humans and animals, but there are several
      plant-specific ones. This review briefly introduces xenobiotic-metabolizing
      enzymes in plants and summarizes present information about their action toward
      veterinary drugs. Veterinary drugs are used worldwide to treat diseases and
      protect animal health. However, veterinary drugs are also unwantedly introduced
      into environment mostly via animal excrements, they persist in the environment
      for a long time and may impact on the non-target organisms. Plants are able to
      uptake, transform the veterinary drugs to non- or less-toxic compounds and store
      them in the vacuoles and cell walls. This ability may protect not only plant
      themselves but also other organisms, predominantly invertebrates and wild
      herbivores. The aim of this review is to emphasize the importance of plants in
      detoxification of veterinary drugs in the environment. The results of studies,
      which dealt with transport and biotransformation of veterinary drugs in plants,
      are summarized and evaluated. In conclusion, the risks and consequences of
      veterinary drugs in the environment and the possibilities of phytoremediation
      technologies are considered and future perspectives are outlined.

PMID- 26289100
TI  - The rise and decline in Salmonella enterica serovar Enteritidis outbreaks
      attributed to egg-containing foods in the United States, 1973-2009.
AB  - Salmonella enterica causes an estimated 1 million domestically acquired foodborne
      illnesses annually. Salmonella enterica serovar Enteritidis (SE) is among the top
      three serovars of reported cases of Salmonella. We examined trends in SE
      foodborne outbreaks from 1973 to 2009 using Joinpoint and Poisson regression. The
      annual number of SE outbreaks increased sharply in the 1970s and 1980s but
      declined significantly after 1990. Over the study period, SE outbreaks were most
      frequently attributed to foods containing eggs. The average rate of SE outbreaks
      attributed to egg-containing foods reported by states began to decline
      significantly after 1990, and the proportion of SE outbreaks attributed to egg
      containing foods began declining after 1997. Our results suggest that
      interventions initiated in the 1990s to decrease SE contamination of shell eggs
      may have been integral to preventing SE outbreaks. 

PMID- 26289101
TI  - The benefits of exercise for patients with non-alcoholic fatty liver disease.
AB  - As exercise is now an established therapy for the management of non-alcoholic
      fatty liver disease (NAFLD), recent investigations have sought to identify the
      optimal dose (type, intensity and amount) of exercise for hepatic benefit. Here,
      the authors discuss the following: the role of aerobic exercise for the
      modulation of hepatic steatosis; the limited evidence for the role of resistance
      training in reducing liver fat; the lack of evidence from clinical trials on the
      role of exercise in non-alcoholic steatohepatitis; and the benefits of exercise
      for patients with NAFLD, beyond steatosis. Based on current evidence, the authors
      provide recommendations for exercise prescription for patients with NAFLD. 

PMID- 26289102
TI  - New medical strategies for the management of acute diverticulitis.
AB  - Acute diverticulitis, defined as acute inflammation of a colonic diverticulum, is
      a common emergency presentation managed by both surgeons and physicians. There
      have been advances in the medical treatments offered to patients in recent years.
      Factors predisposing individuals to the development of acute diverticulitis
      include obesity, smoking, lack of physical activity and medication use, such as
      NSAIDs. Although widely used, there is limited evidence on the efficacy of
      individual antibiotic regimens and antibiotic treatment may not be required in
      all patients. Mesalazine seems to be the only effective treatment for the primary
      prevention of acute diverticulitis. Finally, evidence of effective measures for
      the prevention of recurrence is lacking. Furthermore, high-quality randomized
      controlled trials are required for medical treatments in patients with acute
      diverticulitis, if management is to be evidence based. 

PMID- 26289103
TI  - Systematic review and meta-analysis of the association between IL18RAP rs917997
      and CCR3 rs6441961 polymorphisms with celiac disease risks.
AB  - OBJECTIVES: We performed a systematic review and meta-analysis to estimate the
      polymorphism effects of IL18RAP and CCR3 on celiac disease susceptibility.
      METHODS: PubMed and Web of Science databases were searched (to June 2015) on
      IL18RAP rs917997 and CCR3 rs6441961 polymorphisms. RESULTS: The meta-analysis
      included 16 and 7 studies for rs917997 and rs6441961, respectively. The minor
      risk A allele at both rs917997 and rs6441961 carried risks (odds ratios) of 1.24
      (95% CI 1.18-1.31) and 1.21 (95% CI 1.12-1.31), respectively. These alleles
      contributed to increase risks in all celiac disease patients by 5.04 and 6.35%.
      The estimated lambdas were 0.73 and 0.51, suggesting that an additive model would
      be the best choice for both gene effects. CONCLUSIONS: This meta-analysis
      provides robust estimates that IL18RAP rs917997 and CCR3 rs6441961 are potential
      risk factors for celiac disease in European populations. Studies are needed to
      confirm these findings in different ethnicities.

PMID- 26289104
TI  - The oral refeeding trilemma of acute pancreatitis: what, when and who?
AB  - Tolerance of oral refeeding is an essential goal of nutritional management of
      acute pancreatitis. However, oral feeding intolerance remains one of the most
      common complications in patients with this disease. It often results in longer
      periods of hospitalization, increased treatment costs, increased risk of
      readmission, and reduced quality of life. The traditional practice involves
      keeping patients nil by mouth followed by gradual stepwise reintroduction of
      food. However, it does not have a solid evidence base and, hence, there is
      increasing interest in determining alternative strategies that may be beneficial
      in reducing the occurrence of oral feeding intolerance. This review focuses on
      the randomized controlled trials that investigated the key questions informing
      the nutritional management of acute pancreatitis: when to feed, what to feed and
      who is in charge of the decision-making. 

PMID- 26289105
TI  - Calix[4]arene Based Highly Efficient Fluorescent Sensor for Au(3+) and I(.).
AB  - This approach disclose the selective fluorogenic ion sensing ability of
      5,11,17,23-tetratertbutyl-25,27-bis((2hydroxynaphthylimino)1,2
      ethylenediaminecarbonylmethoxy)-26,28 dihydroxycalix[4]arene (C4NSB). Binding
      property of receptor probed by using selected various cations and anions with
      conferring of results that demonstrates 'turn-off' fluorescence response and
      significantly high chromogenic selectivity toward Au(3+) and I(-). Furthermore,
      selective nature of receptor was investigated in the presence of different co
      existing competing ions. The limit of detection (LOD) for Au(3+) and I(-) was
      determined as 1.5 * 10(-5) and 4.5 * 10(-6) M respectively. Receptor C4NSB form
      (1:1) stoichiometric complex with both ions and their binding constants were
      calculated as 8.0 * 10(2) for Au(3+) and 15.6 * 10(2) M(-1) for I(-). Complexes
      were also characterized through FT-IR spectroscopy.

PMID- 26289106
TI  - Ion manipulations in structures for lossless ion manipulations (SLIM):
      computational evaluation of a 90 degrees  turn and a switch.
AB  - The process of redirecting ions through 90 degrees  turns and 'tee' switches
      utilizing Structures for Lossless Ion Manipulations (SLIM) was evaluated at 4
      Torr pressure using SIMION simulations and theoretical methods. The nature of
      pseudo-potential in SLIM-tee structures has also been explored. Simulations show
      that 100% transmission efficiency in SLIM devices can be achieved with guard
      electrode voltages lower than ~10 V. The ion plume width in these conditions is
      ~1.6 mm while at lower guard voltages lead to greater plume widths. Theoretical
      calculations show marginal loss of ion mobility resolving power (<5%) during ion
      turn due to the finite plume widths (i.e. race track effect). More robust SLIM
      designs that reduce the race track effect while maximizing ion transmission are
      also reported. In addition to static turns, the dynamic switching of ions into
      orthogonal channels was also evaluated both using SIMION ion trajectory
      simulations and experimentally. Simulations and theoretical calculations were in
      close agreement with experimental results and were used to develop more refined
      SLIM designs. 

PMID- 26289108
TI  - Effects of multivalent histamine supported on gold nanoparticles: activation of
      histamine receptors by derivatized histamine at subnanomolar concentrations.
AB  - Colloidal gold nanoparticles with a functionalized ligand shell were synthesized
      and used as new histamine receptor agonists. Mercaptoundecanoic acid moieties
      were attached to the surface of the nanoparticles and derivatized with native
      histamine. The multivalent presentation of the immobilized ligands carried by the
      gold nanoparticles resulted in extremely low activation concentrations for
      histamine receptors on rat colonic epithelium. As a functional read-out system,
      chloride secretion resulting from stimulation of neuronal and epithelial
      histamine H1 and H2 receptors was measured in Ussing chamber experiments. These
      responses were strictly attributed to the histamine entities as histamine-free
      particles Au-MUDOLS or the monovalent ligand AcS-MUDA-HA proved to be
      ineffective. The vitality of the tissues used was not impaired by the
      nanoparticles. 

PMID- 26289109
TI  - Iodanes as Trifluoromethylation Reagents.
AB  - This chapter describes synthesis, structural properties, activation modes, and
      applications of hypervalent iodine reagents for trifluoromethylation, thereby
      focusing on recent advances. 

PMID- 26289107
TI  - The involvement of osteopontin and matrix metalloproteinase- 9 in the migration
      of endometrial epithelial cells in patients with endometriosis.
AB  - BACKGROUND: Endometriosis, which shares certain characteristics with cancers, may
      cause abnormal expression of proteins involved in cell migration. Endometrial
      epithelial cells (EECs) are believed to play an important role in endometriotic
      migration. The aim of this study was to investigate the relationship between the
      expression of osteopontin (OPN) and matrix metalloproteinase-9 (MMP-9) in
      endometriotic migration. METHODS: We performed primary culture of EECs and
      investigated the expression of OPN and MMP-9 in EECs regulated by 17beta
      estradiol (E2). OPN-specific siRNA interference was used to down-regulate OPN and
      to explore the corresponding change in MMP-9 expression. Real-time RT-PCR,
      western blot analysis and flow cytometry were used to determine the expression
      levels of OPN and MMP-9. Gelatin zymography was performed to observe the
      enzymatic activity of MMP-9 in conditioned media. Transwell and wound scratch
      assays were performed to investigate the migration ability of EECs. RESULTS: The
      expression levels of OPN and MMP-9 in normal EECs (NEECs) were inferior to those
      in EECs from patients with endometriosis (EEECs). The expression levels of OPN
      and MMP-9 from stage III/IV EEECs and secretory-phase EECs were higher than those
      of stage I/II EEECs or proliferative-phase EECs. The expression levels of OPN and
      MMP-9 in EEECs were increased by E2 treatment and remarkably decreased by siRNA
      interference. Active MMP-9 expression increased with E2 treatment and decreased
      with siRNA treatment in EEECs compared with the same treatments in NEECs. The
      migratory abilities of EEECs were enhanced after cells were treated with E2; in
      contrast, these abilities were reduced by siRNA interference. In NEECs, active
      MMP-9 and cellular migration abilities were only minimally influenced by E2 and
      siRNA treatment. CONCLUSIONS: The present study suggests that the up-regulation
      of MMP-9 via activation of OPN induced by estrogen may correlate with the
      migration of endometrial epithelial cells in patients with endometriosis.

PMID- 26289110
TI  - In vitro evaluation of the effects of protein-polyphenol-polysaccharide
      interactions on (+)-catechin and cyanidin-3-glucoside bioaccessibility.
AB  - The bioaccessibility of cyanidin-3-glucoside and (+)-catechin in model solutions
      when beta-lactoglobulin (beta-LG) and pectin/chitosan are present was
      investigated using an in vitro model simulating gastrointestinal conditions. In
      the mouth, the free cyanidin content increased (+) 90 and 14% while the (+)
      catechin content decreased (-) 23 and 13%, respectively for mixtures with -pectin
      and -beta-LG-pectin. Under gastric conditions, the cyanidin content decreased 85
      and 28% for mixtures with -pectin and -beta-LG-pectin. On the contrary, after
      gastric digestion, (+)-catechin bioaccessibility increased and exhibited values
      similar to the original samples for all the systems tested. The transition to the
      intestinal environment induced a significant alteration on both polyphenols and
      this effect was more marked for cyanidin. Systems with pectin allowed obtaining a
      higher content of bioaccessible cyanidin. The gastric conditions promoted an
      increase in the antioxidant capacity, followed by a decrease of it in the
      intestine. The free (+)-catechin and cyanidin-3-glucoside contents decreased when
      exposed to the gastrointestinal tract conditions. However, when incorporated in
      food matrix components, the gastrointestinal tract may act positively on the
      extraction of polyphenols, since they are progressively released from protein and
      polysaccharide bonds, being available for the absorption and to exert their
      biological effects. 

PMID- 26289111
TI  - Initial joint stability affects the outcome after conservative treatment of
      simple elbow dislocations: a retrospective study.
AB  - BACKGROUND: Conservative treatment of simple elbow dislocations can lead to
      complications such as persisting pain and restricted joint mobility. The current
      aim was to identify patients with deteriorated outcome after conservative
      treatment and to investigate a possible association with initial joint
      (in)stability. METHODS: Sixty-eight patients (mean age 37.1 +/- 17.2 years) with
      simple elbow dislocations received conservative treatment. After closed
      reduction, joint stability was tested by varus and valgus stress under
      fluoroscopy. According to the findings under fluoroscopy, three different groups
      of instability could be identified: (1) slight instability (joint angulation <10
      degrees ; n = 49), (2) moderate instability (angulation >=10 degrees ; n = 19)
      and (3) gross instability. Patients with gross instability (re-dislocation under
      stability testing) were treated with primary surgical ligament repair and
      therefore excluded from this study. Additionally, MRIs and radiographs were
      analysed regarding warning signs of instability such as the drop sign and joint
      incongruence. Main outcome parameters were the Mayo Elbow Performance Score
      (MEPS), range of motion (ROM), complications and revision rates. RESULTS: After
      40.7 +/- 20.4 months, the overall MEPS was excellent (94.2 +/- 11.3) with a trend
      of slightly worse clinical results in group 2 (95.8 +/- 9.0 vs. 90.0 +/- 15.2
      points; p = 0.154). In group 1, significantly more patients achieved an excellent
      result regarding the MEPS scoring system (77.6 vs. 52.6 %; p = 0.043) and elbow
      extension was significantly worse in group 2 (5.3 +/- 9.9 degrees  vs. 1.4 +/-
      3.0 degrees ; p = 0.015). Seven treatment complications occurred in group 2 (36.8
      %) compared with two in group 1 (4.1 %, p < 0.0001). Six patients (8.8 %) needed
      secondary surgery with an 8.4-fold higher risk for revision surgery in group 2 (p
      = 0.007). The presence of a positive drop sign or joint incongruence led to
      higher odds ratio (OR) for complications (OR = 15.9) and revision surgery (OR =
      10.3). CONCLUSIONS: This study demonstrates that patients with moderate joint
      instability after simple elbow dislocation have a significantly worse clinical
      outcome, more complications and a higher need for secondary revision surgery
      following conservative treatment compared to patients with slight elbow
      instability.

PMID- 26289112
TI  - Ultrasound-guided hyaluronidase injection in cosmetic complications.

PMID- 26289114
TI  - Catheter-based Renal Artery Denervation for Resistant Hypertension: Promise
      Unfulfilled or Unsettled?
AB  - Resistant hypertension affects approximately 10-15 % of the hypertensive
      population and is associated with an increased occurrence of adverse
      cardiovascular outcomes. Recently, renal denervation (RDN) has emerged as a
      novel, non-pharmacologic therapy for resistant hypertension that is designed to
      ablate the sympathetic nerves distributed around the renal arteries, thus
      diminishing sympathetic nervous system activity and its influence on
      hypertension. RDN appeared to have a powerful BP-lowering effect in early
      clinical trials. However, a pivotal follow-up trial, SYMPLICITY HTN-3, showed no
      additional benefit of the therapy when compared with a sham procedure. Various
      aspects of the trial have been examined to explain this inconsistency, including
      a potent placebo effect and uncertainty about whether RDN actually occurred.
      Further research is needed to clarify the role of RDN in the management of
      resistant hypertension.

PMID- 26289113
TI  - Application of high-field NMR spectroscopy for characterization and quantitation
      of submilligram quantities of isolated natural products.
AB  - We have investigated and compared a number of sample conditions on different NMR
      platforms in the search of maximum SNR and optimal experiment time efficiency for
      structure elucidation and quantitation of natural products. Using restricted
      volume 3 mm Shigemi microcell assembly in conjunction with a 900 MHz NMR
      spectrometer equipped with a 5 mm carbon-sensitive inverse cryoprobe, it was
      possible to achieve a substantial increase in SNR (46-fold) as compared with a
      conventional room temperature 400 MHz instrument. Switching from standard 5 mm
      NMR tube to 3 mm Shigemi microcell assembly typically improved SNR by threefold
      on either 600 or 900 MHz cryoplatform. A quantitation method that relies on a
      calibrated residual protonated NMR solvent signal as internal standard was
      developed using the same hardware setup and restricted sample volume tubes.
      Linearity of the method spans over 3 orders of magnitude, from low microgram to
      milligram quantities. We successfully applied this method to quantify a low
      micrgram sample of paclitaxel, verified by a UV/VIS quantitation measurement.

PMID- 26289116
TI  - Personal Therapy in Psychiatry Residency Training: A National Survey of Canadian
      Psychiatry Residents.
AB  - OBJECTIVE: The authors collected nationally representative data on Canadian
      residents' experiences with and perspectives on personal psychotherapy in their
      psychiatric training. METHODS: A 43-item questionnaire was distributed
      electronically to all current psychiatry residents in Canada (N = 839). RESULTS:
      Four hundred residents from every program across Canada returned the survey
      (response rate 47.7%). The prevalence of personal therapy at any time was 55.3%,
      with 42.8% receiving personal therapy during residency. Of residents who
      undertook personal psychotherapy, 59.3% engaged in weekly therapy, 74.1% received
      psychodynamic psychotherapy, and 81.5% participated in long-term therapy (>1
      year). Personal growth, self-understanding, and professional development were the
      most common reasons for engaging in personal therapy; however, one-third of
      residents did so to alleviate symptoms of depression, anxiety, or other mental
      health concerns. Time was the most important factor impeding residents from
      personal therapy; only 8.8% found stigma to act as a barrier. The vast majority
      of residents rated their experience with personal therapy as having a positive or
      very positive impact on their personal life (84.8%) and overall development as
      psychiatrists (81.8%). For 64% of respondents, personal therapy had an important
      or very important role in psychiatry residency training. Residents who received
      personal therapy rated themselves as better able to understand what happens
      moment by moment during therapy sessions, detect and deal with patients'
      emotional reactions, and constructively use their personal reactions to patients.
      CONCLUSION: Interest in personal therapy remains strong among psychiatry trainees
      in Canada. Residents who engaged in psychotherapy endorsed greater confidence in
      psychotherapy and rated their psychotherapy skills more favorably than those who
      had never been in the patient role, supporting the view of personal therapy as an
      important adjunct to psychotherapy training during residency.

PMID- 26289115
TI  - Anaplasma phagocytophilum Rab10-dependent parasitism of the trans-Golgi network
      is critical for completion of the infection cycle.
AB  - Anaplasma phagocytophilum is an emerging human pathogen and obligate
      intracellular bacterium. It inhabits a host cell-derived vacuole and cycles
      between replicative reticulate cell (RC) and infectious dense-cored (DC)
      morphotypes. Host-pathogen interactions that are critical for RC-to-DC conversion
      are undefined. We previously reported that A. phagocytophilum recruits green
      fluorescent protein (GFP)-tagged Rab10, a GTPase that directs exocytic traffic
      from the sphingolipid-rich trans-Golgi network (TGN) to its vacuole in a guanine
      nucleotide-independent manner. Here, we demonstrate that endogenous Rab10
      positive TGN vesicles are not only routed to but also delivered into the A.
      phagocytophilum-occupied vacuole (ApV). Consistent with this finding, A.
      phagocytophilum incorporates sphingolipids while intracellular and retains them
      when naturally released from host cells. TGN vesicle delivery into the ApV is
      Rab10 dependent, up-regulates expression of the DC-specific marker, APH1235, and
      is critical for the production of infectious progeny. The A. phagocytophilum
      surface protein, uridine monophosphate kinase, was identified as a guanine
      nucleotide-independent, Rab10-specific ligand. These data delineate why Rab10 is
      important for the A. phagocytophilum infection cycle and expand the understanding
      of the benefits that exploiting host cell membrane traffic affords intracellular
      bacterial pathogens. 

PMID- 26289117
TI  - Use of time-resolved spectroscopy as a method to monitor carotenoids present in
      tomato extract obtained using ultrasound treatment.
AB  - INTRODUCTION: Compounds exhibiting antioxidant activity have received much
      interest in the food industry because of their potential health benefits.
      Carotenoids such as lycopene, which in the human diet mainly derives from
      tomatoes (Solanum lycopersicum), have attracted much attention in this aspect and
      the study of their extraction, processing and storage procedures is of
      importance. Optical techniques potentially offer advantageous non-invasive and
      specific methods to monitor them. OBJECTIVES: To obtain both fluorescence and
      Raman information to ascertain if ultrasound assisted extraction from tomato pulp
      has a detrimental effect on lycopene. METHOD: Use of time-resolved fluorescence
      spectroscopy to monitor carotenoids in a hexane extract obtained from tomato pulp
      with application of ultrasound treatment (583 kHz). The resultant spectra were a
      combination of scattering and fluorescence. Because of their different
      timescales, decay associated spectra could be used to separate fluorescence and
      Raman information. This simultaneous acquisition of two complementary techniques
      was coupled with a very high time-resolution fluorescence lifetime measurement of
      the lycopene. RESULTS: Spectroscopic data showed the presence of phytofluene and
      chlorophyll in addition to lycopene in the tomato extract. The time-resolved
      spectral measurement containing both fluorescence and Raman data, coupled with
      high resolution time-resolved measurements, where a lifetime of ~5 ps was
      attributed to lycopene, indicated lycopene appeared unaltered by ultrasound
      treatment. Detrimental changes were, however, observed in both chlorophyll and
      phytofluene contributions. CONCLUSION: Extracted lycopene appeared unaffected by
      ultrasound treatment, while other constituents (chlorophyll and phytofluene) were
      degraded.

PMID- 26289118
TI  - The mitochondrial-derived peptide MOTS-c: a player in exceptional longevity?
AB  - Mitochondrial-derived peptides (MDP) are encoded by functional short open reading
      frames in the mitochondrial DNA (mtDNA). These include humanin, and the recently
      discovered mitochondrial open reading frame of the 12S rRNA-c (MOTS-c). Although
      more research is needed, we suggest that the m.1382A>C polymorphism located in
      the MOTS-c encoding mtDNA, which is specific for the Northeast Asian population,
      may be among the putative biological mechanisms explaining the high longevity of
      Japanese people. 

PMID- 26289119
TI  - Unsheltered Homelessness Among Veterans: Correlates and Profiles.
AB  - We identified correlates of unsheltered status among Veterans experiencing
      homelessness and described distinct subgroups within the unsheltered homeless
      Veteran population using data from a screening instrument for homelessness that
      is administered to all Veterans accessing outpatient care at a Veterans Health
      Administration (VHA) facility. Correlates of unsheltered homelessness included
      male gender, white race, older age, lower levels of VHA eligibility, substance
      use disorders, frequent use of VHA inpatient and infrequent use of VHA outpatient
      services, and residing in the West. We identified six distinct subgroups of
      unsheltered Veterans; the tri-morbid frequent users represented the highest need
      group, but the largest group was comprised of Veterans who made highly infrequent
      use of VHA healthcare services. Differences between sheltered and unsheltered
      Veterans and heterogeneity within the unsheltered Veteran population should be
      considered in targeting housing and other interventions. 

PMID- 26289120
TI  - Incorporating resident/fellow training into a robotic surgery program.
AB  - With the rapid uptake of the robotic approach in gynecologic surgery, a thorough
      understanding of the technology, including its uses and limitations, is critical
      to maximize patient outcomes and safety. This review discusses the role of
      training modalities and development of curricula for robotic surgery.
      Furthermore, methods for incorporating the entire surgical team and the process
      of credentialing/maintaining privileges are described.

PMID- 26289121
TI  - Genetic Abnormalities in a Calf with Congenital Increased Muscular Tonus.

PMID- 26289122
TI  - Involvement of inflammation in Alzheimer's disease pathogenesis and therapeutic
      potential of anti-inflammatory agents.
AB  - Alzheimer's disease (AD) is the most common form of dementia. It is characterized
      by beta-amyloid (Abeta) peptide fibrils, which are extracellular depositions of a
      specific protein, and is accompanied by extensive neuroinflammation. Various
      studies have demonstrated risk factors that can affect AD pathogenesis, and they
      include accumulation of Abeta, hyperphosphorylation of tau protein, and
      neuroinflammation. Among these detrimental factors, neuroinflammation has been
      highlighted by epidemiologic studies suggesting that use of anti-inflammatory
      drugs could significantly reduce the incidence of AD. Evidence suggests that
      astrocytes, microglia, and infiltrating immune cells from periphery might
      contribute to or modify the process of neuroinflammation and neurodegeneration in
      AD brains. In addition, recent data indicate that microRNAs may affect
      neuroinflammatory responses in the brain. This article focuses on supportive
      evidence that neuroinflammation plays a critical role in AD development. In
      addition, we depict putative therapeutic capacity of anti-inflammatory drugs for
      AD prevention or treatment. We also discuss pathogenic mechanisms by which
      astrocytes, microglia, T cells and microRNA participate in AD and the
      neuroprotective mechanisms of anti-inflammatory drugs. 

PMID- 26289124
TI  - Apricot kernels: a rare case of cyanide toxicity.

PMID- 26289123
TI  - Corticospinal tract lesion load: An imaging biomarker for stroke motor outcomes.
AB  - OBJECTIVE: The aim of this work was to investigate whether an imaging measure of
      corticospinal tract (CST) injury in the acute phase can predict motor outcome at
      3 months in comparison to clinical assessment of initial motor impairment.
      METHODS: A two-site prospective cohort study followed up a group of first-ever
      ischemic stroke patients using the Upper-Extremity Fugl-Meyer (UE-FM) Scale to
      measure motor impairment in the acute phase and at 3 months. A weighted CST
      lesion load (wCST-LL) was calculated by overlaying the patient's lesion map on
      magnetic resonance imaging with a probabilistic CST constructed from healthy
      control subjects. Regression models were fit to assess the predictive value of
      wCST-LL and compared with initial motor impairment. RESULTS: Seventy-six patients
      (37 from cohort 1 and 39 from cohort 2) completed the study. wCST-LL as well as
      assessment of motor impairment (UE-FM) in the acute phase correlated with motor
      impairment (UE-FM) at 3 months in both cohort 1 (R(2)  = 0.69 vs. R(2)  = 0.67; p
      = 0.43) and cohort 2 (R(2)  = 0.69 vs. R(2)  = 0.62; p = 0.25). In the severely
      impaired subgroup (defined as UE-FM <= 10 at baseline), wCST-LL correlated with
      outcomes significantly better than clinical assessment (R(2)  = 0.47 vs. R(2)  =
      0.11; p = 0.03). In the nonseverely impaired subgroup, stroke patients recovered
      approximately 70% of their maximal recovery potential. All stroke patients in
      both cohorts had poor motor outcomes at 3 months (defined as UE-FM <= 25) when
      wCST-LL was >= 7.0 cc (positive predictive value was 100%). INTERPRETATION: wCST
      LL, an imaging biomarker determined in the acute phase, can predict poststroke
      motor outcomes at 3 months, especially in patients with severe impairment at
      baseline.

PMID- 26289125
TI  - Antidepressant-Like Effects of Sanggenon G, Isolated from the Root Bark of Morus
      alba, in Rats: Involvement of the Serotonergic System.
AB  - The root bark of Morus alba is commonly used as an alternative medicine due to
      its numerous health benefits in humans. However, the antidepressant effects of
      various active components from M. alba have not been fully elucidated. In this
      study, we aimed to determine whether sanggenon G, an active compound isolated
      from the root bark of M. alba, exhibited antidepressant-like activity in rats
      subjected to forced swim test (FST)-induced depression. Acute treatment of rats
      with sanggenon G (30 mg/kg, intraperitoneally (i.p.)) significantly reduced
      immobility time and increased swimming time without any significant change in
      climbing. Rats treated with sanggenon G also exhibited a decrease in the limbic
      hypothalamic-pituitary-adrenal (HPA) axis response to the FST, as indicated by
      attenuation of the corticosterone response and decreased c-Fos immunoreactivity
      in the hypothalamic paraventricular nucleus (PVN). In addition, the
      antidepressant-like effects of sanggenon G were significantly inhibited by
      WAY100635 (1 mg/kg, i.p.; a selective 5-hydroxytryptamine1A (5-HT1A) receptor
      antagonist), but not SCH23390 (0.05 mg/kg, i.p.; a dopamine D1 receptor
      antagonist). Our findings suggested that the antidepressant-like effects of
      sanggenon G were mediated by an interaction with the serotonergic system. Further
      studies are needed to evaluate the potential of sanggenon G as an alternative
      therapeutic approach for the treatment of depression. 

PMID- 26289126
TI  - Twist1 regulates the epithelial-mesenchymal transition via the NF-kappaB pathway
      in papillary thyroid carcinoma.
AB  - Expression of the oncogene Twist1 is correlated with tumor development and
      metastasis. Recent studies have suggested that the epithelial-to-mesenchymal
      transition (EMT) is necessary for tumor progression and metastases. Little is
      known concerning the role of Twist1 and EMT in thyroid cancer. In the present
      work, the expression levels of Twist1 and one marker of EMT, vimentin, were
      measured in papillary thyroid carcinoma (PTC). The results showed Twist1
      expression to be correlated only with cancer lymph node metastases (P = 0.004)
      and not with other clinicopathological indicators. Moreover, Twist1 expression
      was positively correlated with the expression of vimentin (r = 0.408, P = 0.003).
      In vitro studies further indicated that reducing Twist1 expression using short
      hairpin RNA against Twist1 can decrease the invasive and metastatic properties of
      PTC cells and that the down-regulation of Twist1 can reverse EMT by increasing
      the expression of E-cadherin and down-regulating the expression of vimentin in
      the PTC cell line IHH-4. To investigate the effects on Twist1, the PTC cell lines
      TPC-1 and BCPAP were treated with TNF-alpha, resulting in Twist1 up-regulation
      that was dependent on NF-kappaB activation. After the inhibition of NF-kappaB
      activity with Bay11-7082, the Twist1 mRNA and protein levels could not be
      increased. The decline in the Twist1 mRNA and protein levels rendered the cancer
      cells less invasive. Thus, we conclude that Twist1 plays an important role in the
      EMT of PTC via the NF-kappaB pathway.

PMID- 26289127
TI  - Spindle epithelial tumor with thymus-like differentiation (SETTLE): clinical
      pathological features, differential pathological diagnosis and therapy.
AB  - Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a very rare
      tumor of the thyroid gland. An algorithm for the diagnosis and treatment of
      SETTLE has yet to be established. The aim of this study was to identify all case
      reports of SETTLE and to compare the clinical-pathological features and therapy
      of the cases identified. We performed a PubMed search for case reports of SETTLE
      in English published up to November 2014 in which "SETTLE" and "Spindle
      epithelial tumor with thymus-like differentiation" were keywords. We identified
      35 articles for a total of 42 cases. We found that SETTLE usually occurs in
      children and adolescents as an asymptomatic neck mass. Thyroid function tests and
      tumor markers are invariably within normal range in all patients, and fine needle
      aspiration biopsy is rarely diagnostic for SETTLE. All 42 patients had undergone
      thyroidectomy. After surgical resection, chemotherapy (adjuvant or first/second
      line treatment) and/or radiotherapy were administered to control tumor growth in
      cases with metastatic involvement. Although SETTLE presents a low-grade
      malignancy, it can metastasize to lymph nodes, the mediastinum, lung, vertebrae,
      and kidney even many years after the initial diagnosis. SETTLE may have a good
      prognosis if appropriately treated at initial presentation and if patients
      undergo long-term monitoring with regular clinical and morphological evaluations.

PMID- 26289128
TI  - Effects of denosumab on peripheral lymphocyte subpopulations.

PMID- 26289136
TI  - Have research assessment exercises improved the quality of nursing research?

PMID- 26289138
TI  - Aqueous Titanium Trichloride Promoted Reductive Cyclization of o-Nitrostyrenes to
      Indoles: Development and Application to the Synthesis of Rizatriptan and
      Aspidospermidine.
AB  - Treatment of o-nitrostyrenes with aqueous TiCl3 solution at room temperature
      afforded indoles through a formal reductive C(sp(2) )-H amination process. A
      range of functions such as halides (Cl, Br), carbonyl (ester, carbamate), cyano,
      hydroxy, and amino groups were tolerated. From beta,beta-disubstituted o
      nitrostyrenes, 2,3-disubstituted indoles were formed by a domino
      reduction/cyclization/migration process. Mild conditions, simple experimental
      procedure, ready accessibility of the starting materials and good to excellent
      yields characterize the present transformation. The methodology was used as a key
      step in a concise synthesis of rizatriptan and a formal total synthesis of
      aspidospermidine. 

PMID- 26289137
TI  - Evidence for the use of demeclocycline in the treatment of hyponatraemia
      secondary to SIADH: a systematic review.
AB  - AIMS: Hyponatraemia (HN) is the most common electrolyte balance disorder in
      clinical practice. Since the 1970s, demeclocycline has been used in some
      countries to treat chronic HN secondary to syndrome of inappropriate antidiuretic
      hormone secretion (SIADH). The precise mechanism of action of demeclocycline is
      unclear, but has been linked to the induction of nephrogenic diabetes insipidus.
      Furthermore, the safety profile of demeclocycline is variable with an
      inconsistent time to onset, and a potential for complications. There has been no
      systematic evaluation of the use of demeclocycline for the treatment of HN
      secondary to SIADH to date. A systematic literature review was performed to
      obtain an insight into the clinical safety and efficacy of demeclocycline for
      this condition. METHODS: Embase(TM) , MEDLINE((r)) , MEDLINE((r)) In-Process, and
      The Cochrane Library were searched on two occasions using MeSH terms combined
      with free-text terms. References were screened by two independent reviewers.
      Relevant publications were then extracted by two independent reviewers, with a
      third reviewer collating and finalising extractions. RESULTS: The searches
      returned a total of 705 hits. 632 abstracts were screened after the removal of
      duplicates. Following screening, 35 full-length publications were reviewed. Of
      these, 17 were excluded, resulting in 18 studies deemed relevant for data
      extraction. Two were randomised controlled trials (RCTs), 16 were non-RCTs, and
      10 were case reports. DISCUSSION: Although most reports suggest that
      demeclocycline can address serum sodium levels in specific patients with HN,
      efficacy is variable, and may depend upon the underlying aetiology.
      Demeclocycline dose adjustments can be complex, and as its use in clinical
      practice is not well defined, it can differ between healthcare professionals.
      CONCLUSION: There is a lack of clinical and economic evidence supporting the use
      of demeclocycline for HN secondary to SIADH. Patients receiving demeclocycline
      for HN secondary to SIADH must be closely monitored.

PMID- 26289129
TI  - Shear stress mediates exocytosis of functional TRPV4 channels in endothelial
      cells.
AB  - Mechanosensitive ion channels are implicated in the biology of touch, pain,
      hearing and vascular reactivity; however, the identity of these ion channels and
      the molecular basis of their activation is poorly understood. We previously found
      that transient receptor potential vanilloid 4 (TRPV4) is a receptor operated ion
      channel that is sensitised and activated by mechanical stress. Here, we
      investigated the effects of mechanical stimulation on TRPV4 localisation and
      activation in native and recombinant TRPV4-expressing cells. We used a
      combination of total internal reflection fluorescence microscopy, cell surface
      biotinylation assay and Ca(2+) imaging with laser scanning confocal microscope to
      show that TRPV4 is expressed in primary vascular endothelial cells and that shear
      stress sensitises the response of TRPV4 to its agonist, GSK1016790A. The
      sensitisation was attributed to the recruitment of intracellular pools of TRPV4
      to the plasma membrane, through the clathrin and dynamin-mediated exocytosis. The
      translocation was dependent on ILK/Akt signalling pathway, release of Ca(2+) from
      intracellular stores and we demonstrated that shear stress stimulated
      phosphorylation of TRPV4 at tyrosine Y110. Our findings implicate calcium
      sensitive TRPV4 translocation in the regulation of endothelial responses to
      mechanical stimulation.

PMID- 26289139
TI  - Lattice-distortion Induced Magnetic Transition from Low-temperature
      Antiferromagnetism to High-temperature Ferrimagnetism in Double Perovskites
      A2FeOsO6 (A = Ca, Sr).
AB  - High-temperature insulating ferrimagnetism is investigated in order to further
      reveal its physical mechanisms, as well as identify potentially important
      scientific and practical applications relative to spintronics. For example,
      double perovskites such as Sr2FeOsO6 and Ca2FeOsO6 are shown to have puzzling
      magnetic properties. The former is a low-temperature antiferromagnet while the
      latter is a high-temperature insulating ferrimagnet. In order to understand the
      underlying mechanisms, we have investigated the frustrated magnetism of A2FeOsO6
      by employing density functional theory and maximally-localized Wannier functions.
      We find lattice distortion enhances the antiferromagnetic nearest-neighboring Fe
      O-Os interaction, however weakens the antiferromagnetic interactions via the Os-O
      O-Os and Fe-O-Os-O-Fe paths, so is therefore responsible for the magnetic
      transition from the low-temperature antiferromagnetism to the high-temperature
      ferrimagnetism as the decrease of the A(2+) ion radii. Also discussed is the
      5d(3)-3d(5) superexchange. We propose that such superexchange is intrinsically
      antiferromagnetic instead of ferromagnetic as previously thought. Our work
      clearly illustrates the magnetic frustration can be effectively relieved by
      lattice distortion, thus paving the way for tuning of complex magnetism in yet
      other 3d-5d (4d) double perovskites. 

PMID- 26289140
TI  - Hepatic stellate cells regulate liver immunity to visceral leishmaniasis through
      P110delta-dependent induction and expansion of regulatory T cells in mice.
AB  - Visceral leishmaniasis (VL) is associated with severe immune dysfunction and if
      untreated leads to death. Because the liver is one of the primary target organs
      in VL, unraveling the mechanisms governing the local hepatic immune response is
      important for understanding the immunopathogenesis of VL. We previously reported
      that mice with inactivating knockin mutation in the p110delta gene
      (p110delta(D910A) ) are resistant to VL, due in part to impaired regulatory T
      cell (Treg) expansion. In this study, we investigated the mechanism of this
      resistance by focusing on hepatic stellate cells (HSCs), which are known to
      regulate Treg induction and expansion. We show that HSCs are infected with
      Leishmania donovani in vivo and in vitro and that this infection leads to the
      production of interleukin-2, interleukin-6, and transforming growth factor-beta,
      cytokines known to induce Tregs. We further demonstrate that L. donovani
      infection leads to expansion of HSCs in a p110delta-dependent manner and that
      this correlated with proliferation of hepatic Tregs in vivo. In vitro studies
      clearly show that L. donovani-infected HSCs induce CD4(+) T cells to become Tregs
      and expand Tregs in a p110delta-dependent manner. Targeted depletion of HSCs
      during infection caused a dramatic reduction in liver Treg numbers and
      proliferation, which was associated with a decrease in interleukin-10 production
      by hepatic T cells and a more efficient parasite control. CONCLUSION: These
      results demonstrate the critical role of HSCs in the pathogenesis of VL and
      suggest that the enhanced resistance of p110delta(D910A) mice to L. donovani
      infection is due in part to impaired expansion and inability of their HSCs to
      induce and expand Tregs in the liver.

PMID- 26289141
TI  - Frontolimbic neural circuit changes in emotional processing and inhibitory
      control associated with clinical improvement following transference-focused
      psychotherapy in borderline personality disorder.
AB  - AIMS: Borderline personality disorder (BPD) is characterized by self-regulation
      deficits, including impulsivity and affective lability. Transference-focused
      psychotherapy (TFP) is an evidence-based treatment proven to reduce symptoms
      across multiple cognitive-emotional domains in BPD. This pilot study aimed to
      investigate neural activation associated with, and predictive of, clinical
      improvement in emotional and behavioral regulation in BPD following TFP. METHODS:
      BPD subjects (n = 10) were scanned pre- and post-TFP treatment using a within
      subjects design. A disorder-specific emotional-linguistic go/no-go functional
      magnetic resonance imaging paradigm was used to probe the interaction between
      negative emotional processing and inhibitory control. RESULTS: Analyses
      demonstrated significant treatment-related effects with relative increased dorsal
      prefrontal (dorsal anterior cingulate, dorsolateral prefrontal, and frontopolar
      cortices) activation, and relative decreased ventrolateral prefrontal cortex and
      hippocampal activation following treatment. Clinical improvement in constraint
      correlated positively with relative increased left dorsal anterior cingulate
      cortex activation. Clinical improvement in affective lability correlated
      positively with left posterior-medial orbitofrontal cortex/ventral striatum
      activation, and negatively with right amygdala/parahippocampal activation. Post
      treatment improvements in constraint were predicted by pre-treatment right dorsal
      anterior cingulate cortex hypoactivation, and pre-treatment left posterior-medial
      orbitofrontal cortex/ventral striatum hypoactivation predicted improvements in
      affective lability. CONCLUSIONS: These preliminary findings demonstrate potential
      TFP-associated alterations in frontolimbic circuitry and begin to identify neural
      mechanisms associated with a psychodynamically oriented psychotherapy.

PMID- 26289142
TI  - Production of oncolytic adenovirus and human mesenchymal stem cells in a single
      use, Vertical-Wheel bioreactor system: Impact of bioreactor design on performance
      of microcarrier-based cell culture processes.
AB  - Anchorage-dependent cell cultures are used for the production of viruses, viral
      vectors, and vaccines, as well as for various cell therapies and tissue
      engineering applications. Most of these applications currently rely on planar
      technologies for the generation of biological products. However, as new cell
      therapy product candidates move from clinical trials towards potential
      commercialization, planar platforms have proven to be inadequate to meet large
      scale manufacturing demand. Therefore, a new scalable platform for culturing
      anchorage-dependent cells at high cell volumetric concentrations is urgently
      needed. One promising solution is to grow cells on microcarriers suspended in
      single-use bioreactors. Toward this goal, a novel bioreactor system utilizing an
      innovative Vertical-WheelTM technology was evaluated for its potential to support
      scalable cell culture process development. Two anchorage-dependent human cell
      types were used: human lung carcinoma cells (A549 cell line) and human bone
      marrow-derived mesenchymal stem cells (hMSC). Key hydrodynamic parameters such as
      power input, mixing time, Kolmogorov length scale, and shear stress were
      estimated. The performance of Vertical-Wheel bioreactors (PBS-VW) was then
      evaluated for A549 cell growth and oncolytic adenovirus type 5 production as well
      as for hMSC expansion. Regarding the first cell model, higher cell growth and
      number of infectious viruses per cell were achieved when compared with stirred
      tank (ST) bioreactors. For the hMSC model, although higher percentages of
      proliferative cells could be reached in the PBS-VW compared with ST bioreactors,
      no significant differences in the cell volumetric concentration and expansion
      factor were observed. Noteworthy, the hMSC population generated in the PBS-VW
      showed a significantly lower percentage of apoptotic cells as well as reduced
      levels of HLA-DR positive cells. Overall, these results showed that process
      transfer from ST bioreactor to PBS-VW, and scale-up was successfully carried out
      for two different microcarrier-based cell cultures. Ultimately, the data herein
      generated demonstrate the potential of Vertical-Wheel bioreactors as a new
      scalable biomanufacturing platform for microcarrier-based cell cultures of
      complex biopharmaceuticals.

PMID- 26289143
TI  - Predicting Treatment Outcome in PTSD: A Longitudinal Functional MRI Study on
      Trauma-Unrelated Emotional Processing.
AB  - In about 30-50% of patients with posttraumatic stress disorder (PTSD), symptoms
      persist after treatment. Although neurobiological research has advanced our
      understanding of PTSD, little is known about the neurobiology underlying
      persistence of PTSD. Two functional MRI scans were collected from 72 war veterans
      with and without PTSD over a 6- to 8-month interval, during which PTSD patients
      received trauma-focused therapy. All participants performed a trauma-unrelated
      emotional processing task in the scanner. Based on post-treatment symptom
      severity, a distinction was made between remitted and persistent patients.
      Behavioral and imaging measures of trauma-unrelated emotional processing were
      compared between the three groups (remitted patients, N=21; persistent patients,
      N=22; and combat controls, N=25) with repeated-measures (pre- and post-treatment)
      analyses. Second, logistic regression was used to predict treatment outcome.
      Before and after treatment, persistent patients showed a higher dorsal anterior
      cingulate cortex (dACC) and insula response to negative pictures compared with
      remitted patients and combat controls. Before treatment, persistent patients
      showed increased amygdala activation in response to negative pictures compared
      with remitted patients. The remitted patients and combat controls did not differ
      on the behavioral or imaging measures. Finally, higher dACC, insula, and amygdala
      activation before treatment were significant predictors of symptom persistence.
      Our results highlight a pattern of brain activation that may predict poor
      response to PTSD treatment. These findings can contribute to the development of
      alternative or additional therapies. Further research is needed to elucidate the
      heterogeneity within PTSD and describe how differences in neural function are
      related to treatment outcome. Such approaches are critical for defining
      parameters to customize PTSD treatment and improve treatment response rates. 

PMID- 26289144
TI  - Corticostriatal Afferents Modulate Responsiveness to Psychostimulant Drugs and
      Drug-Associated Stimuli.
AB  - The medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) are both integral
      components of the corticobasal ganglia-thalamic circuitry that regulates
      addiction-related behaviors. However, the role of afferent inputs from mPFC to
      NAc in these behaviors is unclear. To address this, we used a Cre-recombinase
      dependent viral vector approach to express G(i/o)-coupled DREADDs (designer
      receptors exclusively activated by designer drugs) selectively in mPFC neurons
      projecting to the NAc and examined the consequences of attenuating activity of
      these neurons on the induction of amphetamine sensitization and on drug taking
      and drug seeking during cocaine self-administration. Surprisingly, decreasing
      mPFC afferent activity to the NAc only transiently reduced locomotor
      sensitization and had no effect on drug taking during cocaine self
      administration. However, inhibiting corticostriatal afferent activity during
      sensitization subsequently enhanced conditioned responding. In addition, this
      manipulation during drug self-administration resulted in slower rates of
      extinction and increased responding during drug prime-induced reinstatement-an
      effect that was normalized by inhibiting these corticostriatal afferents
      immediately before the drug prime. These results suggest that dampening cortical
      control over the NAc during drug exposure may lead to long-term changes in the
      ability of drugs and associated stimuli to drive behavior that has important
      implications for guiding treatments to prevent relapse.

PMID- 26289145
TI  - The Dual Hypocretin Receptor Antagonist Almorexant is Permissive for Activation
      of Wake-Promoting Systems.
AB  - The dual hypocretin receptor (HcrtR) antagonist almorexant (ALM) may promote
      sleep through selective disfacilitation of wake-promoting systems, whereas
      benzodiazepine receptor agonists (BzRAs) such as zolpidem (ZOL) induce sleep
      through general inhibition of neural activity. Previous studies have indicated
      that HcrtR antagonists cause less-functional impairment than BzRAs. To gain
      insight into the mechanisms underlying these differential profiles, we compared
      the effects of ALM and ZOL on functional activation of wake-promoting systems at
      doses equipotent for sleep induction. Sprague-Dawley rats, implanted for EEG/EMG
      recording, were orally administered vehicle (VEH), 100 mg/kg ALM, or 100 mg/kg
      ZOL during their active phase and either left undisturbed or kept awake for 90
      min after which their brains were collected. ZOL-treated rats required more
      stimulation to maintain wakefulness than VEH- or ALM-treated rats. We measured
      Fos co-expression with markers for wake-promoting cell groups in the lateral
      hypothalamus (Hcrt), tuberomammillary nuclei (histamine; HA), basal forebrain
      (acetylcholine; ACh), dorsal raphe (serotonin; 5HT), and singly labeled Fos(+)
      cells in the locus coeruleus (LC). Following SD, Fos co-expression in Hcrt, HA,
      and ACh neurons (but not in 5HT neurons) was consistently elevated in VEH- and
      ALM-treated rats, whereas Fos expression in these neuronal groups was unaffected
      by SD in ZOL-treated rats. Surprisingly, Fos expression in the LC was elevated in
      ZOL- but not in VEH- or ALM-treated SD animals. These results indicate that Hcrt
      signaling is unnecessary for the activation of Hcrt, HA, or ACh wake-active
      neurons, which may underlie the milder cognitive impairment produced by HcrtR
      antagonists compared to ZOL.

PMID- 26289146
TI  - Cannabinoids and Glucocorticoids in the Basolateral Amygdala Modulate Hippocampal
      Accumbens Plasticity After Stress.
AB  - Acute stress results in release of glucocorticoids, which are potent modulators
      of learning and plasticity. This process is presumably mediated by the
      basolateral amygdala (BLA) where cannabinoids CB1 receptors have a key role in
      regulating the hypothalamic-pituitary-adrenal (HPA) axis. Growing attention has
      been focused on nucleus accumbens (NAc) plasticity, which regulates mood and
      motivation. The NAc integrates affective and context-dependent input from the BLA
      and ventral subiculum (vSub), respectively. As our previous data suggest that the
      CB1/2 receptor agonist WIN55,212-2 (WIN) and glucocorticoid receptor (GR)
      antagonist RU-38486 (RU) can prevent the effects of stress on emotional memory,
      we examined whether intra-BLA WIN and RU can reverse the effects of acute stress
      on NAc plasticity. Bilateral, ipsilateral, and contralateral BLA administration
      of RU or WIN reversed the stress-induced impairment in vSub-NAc long-term
      potentiation (LTP) and the decrease in cAMP response element-binding protein
      (CREB) activity in the NAc. BLA CB1 receptors were found to mediate the
      preventing effects of WIN on plasticity, but not the preventing effects of RU,
      after stress. Inactivating the ipsilateral BLA, but not the contralateral BLA,
      impaired LTP. The possible mechanisms underlying the effects of BLA on NAc
      plasticity are discussed; the data suggest that BLA-induced changes in the NAc
      may be mediated through neural pathways in the brain's stress circuit rather than
      peripheral pathways. The results suggest that glucocorticoid and cannabinoid
      systems in the BLA can restore normal function of the NAc and hence may have a
      central role in the treatment of a variety of stress-related disorders. 

PMID- 26289149
TI  - [Autism Spectrum Disorder and DSM-5: Spectrum or Cluster?].
AB  - Within the new DSM-5, the currently differentiated subgroups of "Autistic
      Disorder" (299.0), "Asperger's Disorder" (299.80) and "Pervasive Developmental
      Disorder" (299.80) are replaced by the more general "Autism Spectrum Disorder".
      With regard to a patient-oriented and expedient advising therapy planning,
      however, the issue of an empirically reproducible and clinically feasible
      differentiation into subgroups must still be raised. Based on two Autism-rating
      scales (ASDS and FSK), an exploratory two-step cluster analysis was conducted
      with N=103 children (age: 5-18) seen in our social-pediatric health care centre
      to examine potentially autistic symptoms. In the two-cluster solution of both
      rating scales, mainly the problems in social communication grouped the children
      into a cluster "with communication problems" (51 % and 41 %), and a cluster
      "without communication problems". Within the three-cluster solution of the ASDS,
      sensory hypersensitivity, cleaving to routines and social-communicative problems
      generated an "autistic" subgroup (22%). The children of the second cluster
      ("communication problems", 35%) were only described by social-communicative
      problems, and the third group did not show any problems (38%). In the three
      cluster solution of the FSK, the "autistic cluster" of the two-cluster solution
      differentiated in a subgroup with mainly social-communicative problems (cluster
      1) and a second subgroup described by restrictive, repetitive behavior. The
      different cluster solutions will be discussed with a view to the new DSM-5
      diagnostic criteria, for following studies a further specification of some of the
      ASDS and FSK items could be helpful.

PMID- 26289147
TI  - Antibiotic resistance of Streptococcus agalactiae isolated from pregnant women in
      Garankuwa, South Africa.
AB  - BACKGROUND: This study was undertaken to determine the susceptibility profile and
      the mechanism of antibiotic resistance in Group B streptococcus (GBS) isolates
      detected in vaginal and rectal swabs from pregnant women attending Dr George
      Mukhari Academic Hospital, a University Teaching Hospital in Pretoria, South
      Africa. METHODS: The samples were collected over an 11-month period, cultured on
      selective media (colistin and nalidixic acid agar and Todd-Hewitt broth), and GBS
      positively identified by using different morphological and biochemical tests. The
      susceptibility testing was done using the Kirby-Bauer and E test methods
      according to CLSI guidelines 2012. The D test method was used for the detection
      of inducible clindamycin resistance. Multiplex PCR with specific primers was used
      to detect different genes coding for resistance. RESULTS: Out of 413 samples
      collected, 128 (30.9%) were positive with GBS. The susceptibility testing
      revealed that 100% of isolates were sensitive to penicillin, ampicillin,
      vancomycin and high level gentamicin. Erythromycin and clindamycin resistance was
      21.1 and 17.2%, respectively, in which 69% had harboured constitutive macrolide,
      lincosamide and streptogramin B (MLS(B)), 17.4% had inducible MLS(B). The M and L
      phenotypes were present in 6.8% each. The methylation of target encoded by ermB
      genes was the commonest mechanism of resistance observed in 55% of isolates, 38%
      of isolates had both ermB and linB genes and efflux pump mediated by mefA genes
      was also distributed among the isolates. CONCLUSIONS: The study reaffirmed the
      appropriateness of penicillin as the antibiotic of choice for treating GBS
      infection. However it identified the challenges of resistance to macrolides and
      lincosamides used as alternative drugs for individuals allergic to penicillin.
      More GBS treatment options for penicillin allergic patients need to be researched
      on.

PMID- 26289150
TI  - [On the Effectiveness of the Prevention Program JobFit: A Comparison of Different
      Class Levels].
AB  - The JobFit-Training for adolescents (Petermann u. Petermann, 2010) is a well
      documented behavioural psychological prevention program for students from the
      eighth grade and up. The present study examines the results of the evaluation of
      the practical implementation of the training over the course of two years. Data
      from 828 students could be collected in two measurements, before and after the
      intervention, out of which 323 were eighth-graders and 505 were ninth-graders.
      The analysis showed that eighth-graders profit more with regards to acquiring
      knowledge through the training than ninth-graders do. However, unlike male eighth
      graders, female eighth-graders were unable to furthermore improve their social
      competences through the training. On the other hand the ninth-graders profit from
      the training in both groups with regards to their social competences. 

PMID- 26289151
TI  - [Development and Validation of the Revenge Fantasy Inventory for Adolescents (RFI
      J)].
AB  - The Revenge Fantasy Inventory for Adolescents (RFI-J) is a paper-pencil
      questionnaire that aims at assessing revenge fantasies of adolescents and
      facilitates an interpersonal comparison of revenge fantasies. The RFI-J assesses
      components concerning the subjective relevance of revenge fantasies, for example
      a coherence with emotion regulation and adolescent's attitudes towards revenge.
      In addition, the content of revenge fantasies is measured. The psychometric
      properties of revenge fantasies were analysed in two studies: In the first study
      an early concept of the instrument (consisting of two parts: assessment of
      subjective relevance of the fantasies and assessment of revenge fantasy content)
      was presented to 248 students (123 males) with an average age of 14.9 years
      (SD=0.89; Range=14-18 years). Using Principal Component Analysis (PCA) both parts
      of the instrument were dimensionalised. Subsequently, scales were built and a
      first version of the inventory was developed. In a second study with another
      sample consisting of 88 students (48 males) with an average age of 14.9 years
      (SD=0.72; Range=14-17 years) four of the factors which had been found in the
      first study were replicated. Furthermore, correlations were found between the RFI
      J and measures of aggression, measures of pro-sociality, as well as measures of
      physical and psychological complaints. The developed test in its current version
      consist of two parts (18 and 6 Items).

PMID- 26289152
TI  - ["What I don't Appreciate in Real Life": Online Role Playing Game Addiction of an
      Adolescent--Case Study].
AB  - The present article aims to provide an insight into the life story of a computer
      game addicted adolescent. Here, the relationship between the symptom game
      addiction, the family as a reference framework, the game's characteristics, as
      well as the subjective emotional state of the adolescent are of particular
      interest. An emphasis is also laid on the psychodynamically approached question
      of the impact of infantile and current relationship experiences (both within a
      family environment as well as with peers) on personal development. Last, still
      within a psychodynamic framework, we hope to provide a better understanding of
      the role of online computer-game addiction in the process of experiences
      potentially dominated by conflicts. 

PMID- 26289158
TI  - TMalphaDB and TMbetaDB: web servers to study the structural role of sequence
      motifs in alpha-helix and beta-barrel domains of membrane proteins.
AB  - BACKGROUND: Membrane proteins represent over 25 % of human protein genes and
      account for more than 60 % of drug targets due to their accessibility from the
      extracellular environment. The increasing number of available crystal structures
      of these proteins in the Protein Data Bank permits an initial estimation of their
      structural properties. DESCRIPTION: We have developed two web servers-TMalphaDB
      for alpha-helix bundles and TMbetaDB for beta-barrels-to analyse the growing
      repertoire of available crystal structures of membrane proteins. TMalphaDB and
      TMbetaDB permit to search for these specific sequence motifs in a non-redundant
      structure database of transmembrane segments and quantify structural parameters
      such as phi and psi backbone dihedral angles, chi1 side chain torsion angle, unit
      bend and unit twist. CONCLUSIONS: The structural information offered by TMalphaDB
      and TMbetaDB permits to quantify structural distortions induced by specific
      sequence motifs, and to elucidate their role in the 3D structure. This specific
      structural information has direct implications in homology modeling of the
      growing sequences of membrane proteins lacking experimental structure. TMalphaDB
      and TMbetaDB are freely available at http://lmc.uab.cat/TMalphaDB and
      http://lmc.uab.cat/TMbetaDB.

PMID- 26289159
TI  - Hematopoietic and nonhematopoietic cells promote Type I interferon- and TLR7
      dependent monocytosis during low-dose LCMV infection.
AB  - Release of inflammatory monocytes from the bone marrow (BM) into the blood is an
      important physiological response to infection, but the mechanisms regulating this
      phenomenon during viral infection are not completely defined. Here, we show that
      low-dose infection with lymphocytic choriomeningitis virus (LCMV) caused rapid,
      transient inflammatory monocytosis that required type I interferon (IFN) and Toll
      like receptor (TLR) 7 signaling. Type I IFN and TLR7 signals were critical for
      induction of IFN-stimulated gene expression and CCR2 ligand upregulation in the
      BM microenvironment in response to LCMV infection. Experiments utilizing BM
      chimeric mice demonstrated that type I IFN and TLR7 signaling on either
      hematopoietic or nonhematopoietic cells was sufficient to initiate monocytosis in
      response to LCMV infection. BM plasmacytoid dendritic cells (pDCs) generated type
      I IFN directly ex vivo, suggesting that pDCs are a hematopoietic contributor of
      type I IFN in the BM early during LCMV infection. Overall, we describe novel
      roles for type I IFN and TLR7 signaling in nonhematopoietic cells and BM pDCs in
      directing IFN-stimulated gene and CCR2 ligand expression in the BM to initiate an
      increase in blood inflammatory monocytes during viral infection.

PMID- 26289160
TI  - The Multiple DSF-family QS Signals are Synthesized from Carbohydrate and Branched
      chain Amino Acids via the FAS Elongation Cycle.
AB  - Members of the diffusible signal factor (DSF) family are a novel class of quorum
      sensing (QS) signals in diverse Gram-negative bacteria. Although previous studies
      have identified RpfF as a key enzyme for the biosynthesis of DSF family signals,
      many questions in their biosynthesis remain to be addressed. In this study with
      the phytopathogen Xanthomonas campestris pv. campestris (Xcc), we show that Xcc
      produces four DSF-family signals (DSF, BDSF, CDSF and IDSF) during cell culture,
      and that IDSF is a new functional signal characterized as cis-10-methyl-2
      dodecenoic acid. Using a range of defined media, we further demonstrate that Xcc
      mainly produces BDSF in the presence of carbohydrates; leucine and valine are the
      primary precursor for DSF biosynthesis; isoleucine is the primary precursor for
      IDSF biosynthesis. Furthermore, our biochemical analyses show that the key DSF
      synthase RpfF has both thioesterase and dehydratase activities, and uses 3
      hydroxydedecanoyl-ACP as a substrate to produce BDSF. Finally, our results show
      that the classic fatty acid synthesis elongation cycle is required for the
      biosynthesis of DSF-family signals. Taken all together, these findings establish
      a general biosynthetic pathway for the DSF-family quorum sensing signals. 

PMID- 26289161
TI  - Restoration of camptothecine production in attenuated endophytic fungus on re
      inoculation into host plant and treatment with DNA methyltransferase inhibitor.
AB  - Fungal endophytes inhabit living tissues of plants without any apparent symptoms
      and in many cases are known to produce secondary metabolites similar to those
      produced by their respective host plants. However on sub-culture, the endophytic
      fungi gradually attenuate their ability to produce the metabolites. Attenuation
      has been a major constraint in realizing the potential of endophytic fungi as an
      alternative source of plant secondary metabolites. In this study, we report
      attempts to restore camptothecine (CPT) production in attenuated endophytic fungi
      isolated from CPT producing plants, Nothapodytes nimmoniana and Miquelia dentata
      when they are passed through their host plant or plants that produce CPT and when
      treated with a DNA methyl transferase inhibitor. Attenuated endophytic fungi that
      traversed through their host tissue or plants capable of synthesizing CPT,
      produced significantly higher CPT compared to the attenuated fungi. Attenuated
      fungus cultured in the presence of 5-azacytidine, a DNA methyltransferase
      inhibitor, had an enhanced CPT content compared to untreated attenuated fungus.
      These results indicate that the attenuation of CPT production in endophytic fungi
      could in principle be reversed by eliciting some signals from plant tissue, most
      likely that which prevents the methylation or silencing of the genes responsible
      for CPT biosynthesis. 

PMID- 26289162
TI  - Shell-vial culture and real-time PCR applied to Rickettsia typhi and Rickettsia
      felis detection.
AB  - Murine typhus is a zoonosis transmitted by fleas, whose etiological agent is
      Rickettsia typhi. Rickettsia felis infection can produces similar symptoms. Both
      are intracellular microorganisms. Therefore, their diagnosis is difficult and
      their infections can be misdiagnosed. Early diagnosis prevents severity and
      inappropriate treatment regimens. Serology can't be applied during the early
      stages of infection because it requires seroconversion. Shell-vial (SV) culture
      assay is a powerful tool to detect Rickettsia. The aim of the study was to
      optimize SV using a real-time PCR as monitoring method. Moreover, the study
      analyzes which antibiotics are useful to isolate these microorganisms from fleas
      avoiding contamination by other bacteria. For the first purpose, SVs were
      inoculated with each microorganism. They were incubated at different temperatures
      and monitored by real-time PCR and classical methods (Gimenez staining and
      indirect immunofluorescence assay). R. typhi grew at all temperatures. R. felis
      grew at 28 and 32  degrees C. Real-time PCR was more sensitive than classical
      methods and it detected microorganisms much earlier. Besides, the assay
      sensitivity was improved by increasing the number of SV. For the second purpose,
      microorganisms and fleas were incubated and monitored in different concentrations
      of antibiotics. Gentamicin, sufamethoxazole, trimethoprim were useful for R.
      typhi isolation. Gentamicin, streptomycin, penicillin, and amphotericin B were
      useful for R. felis isolation. Finally, the optimized conditions were used to
      isolate R. felis from fleas collected at a veterinary clinic. R. felis was
      isolated at 28 and 32  degrees C. However, successful establishment of cultures
      were not possible probably due to sub-optimal conditions of samples. 

PMID- 26289165
TI  - Generation of clonal zebrafish line by androgenesis without egg irradiation.
AB  - Generation of clonal zebrafish will facilitate large-scale genetic screening and
      help us to overcome other biological and biotechnological challenges due to their
      isogenecity. However, protocols for the development of clonal lines have not been
      optimized. Here, we sought to develop a novel method for generation of clonal
      zebrafish by androgenesis induced by cold shock. Androgenetic zebrafish doubled
      haploids (DHs) were induced by cold shock of just-fertilized eggs, and the eggs
      were then heat shocked to double the chromosome set. The yield rate of putative
      DHs relative to the total number of eggs used was 1.10% +/- 0.19%. Microsatellite
      genotyping of the putative DHs using 30 loci that covered all 25 linkage groups
      detected no heterozygous loci, confirming the homozygosity of the DHs. Thus, a
      clonal line was established from sperm of a DH through a second cycle of cold
      shock androgenesis and heat-shock chromosome doubling, followed by genetic
      verification of the isogenic rate confirming the presence of identical DNA
      fingerprints by using amplified fragment length polymorphism markers. In
      addition, our data provided important insights into the cytological mechanisms of
      cold-shock-induced androgenesis. 

PMID- 26289163
TI  - Multimodal treatment of perianal fistulas in Crohn's disease: seton versus anti
      TNF versus advancement plasty (PISA): study protocol for a randomized controlled
      trial.
AB  - BACKGROUND: Currently there is no guideline for the treatment of patients with
      Crohn's disease and high perianal fistulas. Most patients receive anti-TNF
      medication, but no long-term results of this expensive medication have been
      described, nor has its efficiency been compared to surgical strategies. With this
      study, we hope to provide treatment consensus for daily clinical practice with
      reduction in costs. METHODS/DESIGN: This is a multicentre, randomized controlled
      trial. Patients with Crohn's disease who are over 18 years of age, with newly
      diagnosed or recurrent active high perianal fistulas, with one internal opening
      and no anti-TNF usage in the past three months will be considered. Patients with
      proctitis, recto-vaginal fistulas or anal stenosis will be excluded. Prior to
      randomisation, an MRI and ileocolonoscopy are required. All treatment will start
      with seton placement and a course of antibiotics. Patients will then be
      randomised to: (1) chronic seton drainage (with oral 6-mercaptopurine (6MP)) for
      one year, (2) anti-TNF medication (with 6MP) for one year (seton removal after
      six weeks) or (3) advancement plasty after eight weeks of seton drainage (under
      four months anti-TNF and 6MP for one year). The primary outcome parameter is the
      number of patients needing fistula-related re-intervention(s). Secondary outcomes
      are the number of patients with closed fistulas (based on an evaluated MRI score)
      after 18 months, disease activity, quality of life and costs. DISCUSSION: The
      PISA trial is a multicentre, randomised controlled trial of patients with Crohn's
      disease and high perianal fistulas. With the comparison of three generally
      accepted treatment strategies, we will be able to comment on the efficiency of
      the various treatment strategies, with respect to several long-term outcome
      parameters. TRIAL REGISTRATION: Nederlands Trial Register identifier: NTR4137
      (registered on 23 August 2013).

PMID- 26289164
TI  - Neurobiology and sleep disorders in cluster headache.
AB  - Cluster headache is characterized by unilateral attacks of severe pain
      accompanied by cranial autonomic features. Apart from these there are also sleep
      related complaints and strong chronobiological features. The interaction between
      sleep and headache is complex at any level and evidence suggests that it may be
      of critical importance in our understanding of primary headache disorders. In
      cluster headache several interactions between sleep and the severe pain attacks
      have already been proposed. Supported by endocrinological and radiological
      findings as well as the chronobiological features, predominant theories revolve
      around central pathology of the hypothalamus. We aimed to investigate the
      clinical presentation of chronobiological features, the presence of concurrent
      sleep disorders and the relationship with particular sleep phases or phenomena,
      the possible role of hypocretin as well as the possible involvement of cardiac
      autonomic control. We conducted a questionnaire survey on 275 cluster headache
      patients and 145 controls as well an in-patient sleep study including 40 CH
      patients and 25 healthy controls. The findings include: A distinct circannual
      connection between cluster occurrence and the amount of daylight, substantially
      poorer sleep quality in patients compared to controls which was present not only
      inside the clusters but also outside, affected REM-sleep in patients without a
      particular temporal connection to nocturnal attacks, equal prevalence of sleep
      apnea in both patient and control groups, reduced levels of hypocretin-1 in the
      cerebrospinal fluid of patients and finally a blunted response to the change from
      supine to tilted position in the head-up tilt table test indicating a weakened
      sympathoexcitatory or stronger parasympathetic drive. Overall, these findings
      support a theory of involvement of dysregulation in hypothalamic and brainstem
      nuclei in cluster headache pathology. Further, it is made plausible that the
      headache attacks are but one aspect of a more complex syndrome of central
      dysregulation manifesting as sleep-related complaints, sub-clinical autonomic
      dysregulation and of course the severe attacks of unilateral headache. Future
      endeavors should focus on pathological changes which persist in the attack-free
      periods but also heed the possibility of long-lived, cluster-induced pathology.

PMID- 26289166
TI  - Disabled women's experiences of accessing and utilising maternity services when
      they are affected by domestic abuse: a critical incident technique study.
AB  - BACKGROUND: Women and their babies are entitled to equal access to high quality
      maternity care. However, when women fit into two or more categories of
      vulnerability they can face multiple, compound barriers to accessing and
      utilising services. Disabled women are up to three times more likely to
      experience domestic abuse than non-disabled women. Domestic abuse may compromise
      health service access and utilisation and disabled people in general have
      suboptimal access to healthcare services. Despite this, little is known about the
      compounding effects of disability and domestic abuse on women's access to
      maternity care. METHODS: The aim of the study was to identify how women approach
      maternity care services, their expectations of services and whether they are able
      to get the type of care that they need and want. We conducted a qualitative,
      Critical Incident Technique study in Scotland. Theoretically we drew on
      Andersen's model of healthcare use. The model was congruent with our interest in
      women's intended/actual use of maternity services and the facilitators and
      barriers impacting their access to care. Data were generated during 2013 using
      one-to-one interviews. RESULTS: Five women took part and collectively reported 45
      critical incidents relating to accessing and utilising maternity services. Mapped
      to the underpinning theoretical framework, our findings show how the four domains
      of attitudes; knowledge; social norms; and perceived control are important
      factors shaping maternity care experiences. CONCLUSIONS: Positive staff attitude
      and empowering women to have control over their own care is crucial in
      influencing women's access to and utilisation of maternity healthcare services.
      Moreover these are cyclical, with the consequences and outcomes of healthcare use
      becoming part of the enabling or disabling factors affecting future healthcare
      decisions.Further consideration needs to be given to the development of
      strategies to access and recruit women in these circumstances. This will provide
      an opportunity for under-represented and silenced voices to be heard.

PMID- 26289167
TI  - Expression and pathological effects of periostin in human osteoarthritis
      cartilage.
AB  - BACKGROUND: Osteoarthritis (OA) is one of the most common joint diseases in
      elderly people, however, the underlying mechanism of OA pathogenesis is not
      completely clear. Periostin, the extracellular protein, has been shown by cDNA
      array analysis to be highly expressed in OA, but its function is not fully
      understood. The purpose of this study was to examine the expression and function
      of periostin in human OA. METHODS: Human cartilage and synovia samples were used
      for the analysis of periostin expression and function. The human cartilage
      samples were obtained from the knees of patients undergoing total knee
      arthroplasty as OA samples and from the femoral bone head of patients with
      femoral neck fracture as control samples. Quantitative RT-PCR, ELISA, and
      immunohistochemistry were used for analysis of periostin expression in cartilage
      and synovia. Human primary chondrocytes isolated from control cartilage were
      stimulated by periostin, and the alteration of OA related gene expression was
      examined using quantitative RT-PCR. Immunocytochemistry of p65 was performed for
      the analysis of nuclear factor kappa B (NFkappaB) activation. RESULTS: The
      periostin mRNA was significantly higher in OA cartilage than in control
      cartilage. Immunohistochemical analysis of periostin showed that the main
      positive signal was localized in chondrocytes and their periphery matrix near the
      erosive area, with less immunoreactivity in deeper zones. There was positive
      correlation between Mankin score and periostin immunoreactivity. The periostin
      expression was also detected in the fibrotic cartilage and tissue of subchondral
      bone. In cultured human chondrocytes, periostin induced the expression of
      interleukin (IL)-6, IL-8, matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, and
      nitric oxide synthase-2 (NOS2) in a dose- and time-dependent manner. The
      activation of NFkappaB signaling was recognized by the nuclear translocation of
      p65. Periostin-induced upregulation of these genes was suppressed by NFkappaB
      inactivation in chondrocytes. CONCLUSION: Periostin was upregulated in OA
      cartilage, and it may amplify inflammatory events and accelerate OA pathology.

PMID- 26289168
TI  - Treatment of Vancouver type B2 periprosthetic femoral fractures.
AB  - PURPOSE: Stem loosening in both cemented and uncemented total hip arthroplasty is
      the hallmark of the Vancouver type B2 classification of periprosthetic hip
      fractures. METHODS: We discuss the technique we use at our institution for
      treating these fractures. RESULTS: Periprosthetic femoral-shaft fractures are
      associated with a relatively high mortality rate, approximating that of patients
      with hip fractures. Outcomes are directly associated with early mobilisation and
      construct stability. CONCLUSIONS: We recommend performing the procedure only when
      the surgeon is proficient in revision hip surgery and trauma care. A well
      selected portfolio of different stem designs and an array of osteosynthesis
      devices should be available, as well.

PMID- 26289170
TI  - Portfolio boost.

PMID- 26289169
TI  - Enhanced conduction band density of states in intermetallic EuTSi3 (T = Rh, Ir).
AB  - We report on the physical properties of single crystalline EuRhSi3 and
      polycrystalline EuIrSi3, inferred from magnetization, electrical transport, heat
      capacity and (151)Eu Mossbauer spectroscopy. These previously known compounds
      crystallise in the tetragonal BaNiSn3-type structure. The single crystal
      magnetization in EuRhSi3 has a strongly anisotropic behaviour at 2 K with a spin
      flop field of 13 T, and we present a model of these magnetic properties which
      allows the exchange constants to be determined. In both compounds, specific heat
      shows the presence of a cascade of two close transitions near 50 K, and the
      (151)Eu Mossbauer spectra demonstrate that the intermediate phase has an
      incommensurate amplitude modulated structure. We find anomalously large values,
      with respect to other members of the series, for the RKKY Neel temperature, for
      the spin-flop field (13 T), for the spin-wave gap (?20-25 K) inferred from both
      resistivity and specific heat data, for the spin-disorder resistivity in EuIrSi3
      (?240 MUOmega cm) and for the saturated hyperfine field (52 T). The enhanced
      values of the quantities that depend on the electronic density of states at the
      Fermi level, imply that the latter must be strongly enhanced in these two
      materials. EuIrSi3 exhibits a giant magnetoresistance ratio, with values
      exceeding 600% at 2 K in a field of 14 T.

PMID- 26289171
TI  - Rise of the citizen scientist.

PMID- 26289172
TI  - Tackle Nepal's typhoid problem now.

PMID- 26289184
TI  - Greek bailout set to free up research funds.

PMID- 26289185
TI  - Ebola spurs creation of Japan's first maximum-security biolab.

PMID- 26289186
TI  - Most gay and lesbian researchers are out in the lab.

PMID- 26289188
TI  - Superconductivity record sparks wave of follow-up physics.

PMID- 26289187
TI  - China's carbon emissions overestimated.

PMID- 26289189
TI  - Chinese biologists lead outcry over Winter Olympics ski site.

PMID- 26289191
TI  - Policy: Hurricane Katrina's lessons for the world.

PMID- 26289195
TI  - Land reclamation: Halt reef destruction in South China Sea.

PMID- 26289196
TI  - Tribute: India's inspiring former president.

PMID- 26289197
TI  - STEM teaching: Medicine in Europe.

PMID- 26289198
TI  - STEM teaching: The need for wider skills.

PMID- 26289199
TI  - Institutions: Funders must not coerce scientists.

PMID- 26289200
TI  - Dengue virus: Bumps in the road to therapeutic antibodies.

PMID- 26289202
TI  - Astrophysics: Mystery survivor of a supermassive black hole.

PMID- 26289203
TI  - Growing the gas-giant planets by the gradual accumulation of pebbles.
AB  - It is widely held that the first step in forming gas-giant planets, such as
      Jupiter and Saturn, was the production of solid 'cores' each with a mass roughly
      ten times that of the Earth. Getting the cores to form before the solar nebula
      dissipates (in about one to ten million years; ref. 3) has been a major challenge
      for planet formation models. Recently models have emerged in which 'pebbles'
      (centimetre-to-metre-sized objects) are first concentrated by aerodynamic drag
      and then gravitationally collapse to form objects 100 to 1,000 kilometres in
      size. These 'planetesimals' can then efficiently accrete left-over pebbles and
      directly form the cores of giant planets. This model is known as 'pebble
      accretion'; theoretically, it can produce cores of ten Earth masses in only a few
      thousand years. Unfortunately, full simulations of this process show that, rather
      than creating a few such cores, it produces a population of hundreds of Earth
      mass objects that are inconsistent with the structure of the Solar System. Here
      we report that this difficulty can be overcome if pebbles form slowly enough to
      allow the planetesimals to gravitationally interact with one another. In this
      situation, the largest planetesimals have time to scatter their smaller siblings
      out of the disk of pebbles, thereby stifling their growth. Our models show that,
      for a large and physically reasonable region of parameter space, this typically
      leads to the formation of one to four gas giants between 5 and 15 astronomical
      units from the Sun, in agreement with the observed structure of the Solar System.

PMID- 26289205
TI  - Highly saline fluids from a subducting slab as the source for fluid-rich
      diamonds.
AB  - The infiltration of fluids into continental lithospheric mantle is a key
      mechanism for controlling abrupt changes in the chemical and physical properties
      of the lithospheric root, as well as diamond formation, yet the origin and
      composition of the fluids involved are still poorly constrained. Such fluids are
      trapped within diamonds when they form and so diamonds provide a unique means of
      directly characterizing the fluids that percolate through the deep continental
      lithospheric mantle. Here we show a clear chemical evolutionary trend,
      identifying saline fluids as parental to silicic and carbonatitic deep mantle
      melts, in diamonds from the Northwest Territories, Canada. Fluid-rock interaction
      along with in situ melting cause compositional transitions, as the saline fluids
      traverse mixed peridotite-eclogite lithosphere. Moreover, the chemistry of the
      parental saline fluids--especially their strontium isotopic compositions--and the
      timing of host diamond formation suggest that a subducting Mesozoic plate under
      western North America is the source of the fluids. Our results imply a strong
      association between subduction, mantle metasomatism and fluid-rich diamond
      formation, emphasizing the importance of subduction-derived fluids in affecting
      the composition of the deep lithospheric mantle.

PMID- 26289204
TI  - Reduced carbon emission estimates from fossil fuel combustion and cement
      production in China.
AB  - Nearly three-quarters of the growth in global carbon emissions from the burning
      of fossil fuels and cement production between 2010 and 2012 occurred in China.
      Yet estimates of Chinese emissions remain subject to large uncertainty;
      inventories of China's total fossil fuel carbon emissions in 2008 differ by 0.3
      gigatonnes of carbon, or 15 per cent. The primary sources of this uncertainty are
      conflicting estimates of energy consumption and emission factors, the latter
      being uncertain because of very few actual measurements representative of the mix
      of Chinese fuels. Here we re-evaluate China's carbon emissions using updated and
      harmonized energy consumption and clinker production data and two new and
      comprehensive sets of measured emission factors for Chinese coal. We find that
      total energy consumption in China was 10 per cent higher in 2000-2012 than the
      value reported by China's national statistics, that emission factors for Chinese
      coal are on average 40 per cent lower than the default values recommended by the
      Intergovernmental Panel on Climate Change, and that emissions from China's cement
      production are 45 per cent less than recent estimates. Altogether, our revised
      estimate of China's CO2 emissions from fossil fuel combustion and cement
      production is 2.49 gigatonnes of carbon (2 standard deviations = +/-7.3 per cent)
      in 2013, which is 14 per cent lower than the emissions reported by other
      prominent inventories. Over the full period 2000 to 2013, our revised estimates
      are 2.9 gigatonnes of carbon less than previous estimates of China's cumulative
      carbon emissions. Our findings suggest that overestimation of China's emissions
      in 2000-2013 may be larger than China's estimated total forest sink in 1990-2007
      (2.66 gigatonnes of carbon) or China's land carbon sink in 2000-2009 (2.6
      gigatonnes of carbon). 

PMID- 26289208
TI  - A rapid field test for the measurement of bovine serum immunoglobulin G using
      attenuated total reflectance infrared spectroscopy.
AB  - BACKGROUND: Following the recent development of a new approach to quantitative
      analysis of IgG concentrations in bovine serum using transmission infrared
      spectroscopy, the potential to measure IgG levels using technology and a device
      better designed for field use was investigated. A method using attenuated total
      reflectance infrared (ATR) spectroscopy in combination with partial least squares
      (PLS) regression was developed to measure bovine serum IgG concentrations. ATR
      spectroscopy has a distinct ease-of-use advantage that may open the door to
      routine point-of-care testing. Serum samples were collected from calves and adult
      cows, tested by a reference RID method, and ATR spectra acquired. The spectra
      were linked to the RID-IgG concentrations and then randomly split into two sets:
      calibration and prediction. The calibration set was used to build a calibration
      model, while the prediction set was used to assess the predictive performance and
      accuracy of the final model. The procedure was repeated for various spectral data
      preprocessing approaches. RESULTS: For the prediction set, the Pearson's and
      concordance correlation coefficients between the IgG measured by RID and
      predicted by ATR spectroscopy were both 0.93. The Bland Altman plot revealed no
      obvious systematic bias between the two methods. ATR spectroscopy showed a
      sensitivity for detection of failure of transfer of passive immunity (FTPI) of 88
      %, specificity of 100 % and accuracy of 94 % (with IgG <1000 mg/dL as the FTPI
      cut-off value). CONCLUSION: ATR spectroscopy in combination with multivariate
      data analysis shows potential as an alternative approach for rapid quantification
      of IgG concentrations in bovine serum and the diagnosis of FTPI in calves.

PMID- 26289209
TI  - Sustained protein release from hydrogel microparticles using layer-by-layer (LbL)
      technology.
AB  - CONTEXT AND OBJECTIVES: Since most of developed therapeutic proteins are intended
      to treat chronic diseases, patients are prescribed multiple injections for long
      time periods, and therefore, sustained release formulations are much needed.
      However, challenges facing these formulations are quite significant. In this
      context, a model protein, lysozyme (Lys), was loaded on hydrogel microparticles
      (beads) and the ability of layer-by-layer (LbL) coating to control Lys release
      and maintain its activity over a one-month period was investigated. METHODS: LbL
      coating was composed of chondroitin sulfate as a negatively charged
      polyelectrolyte and a biocompatible, hydrolytically degradable poly beta
      aminoester as a positively charged polyelectrolyte. Loading distribution was
      monitored by fluorescence imaging, and followed by depositing a series of LbL
      coatings of different thicknesses. Release of Lys from these formulations was
      studied and activity of released fraction was determined. RESULTS: Lys was loaded
      effectively on hydrogel beads achieving about 9 mg protein/100 mg wet spheres.
      LbL coating was proven successful by monitoring the zeta potential of the beads,
      which was reversed after the addition of each layer. In vitro release studies
      showed sustained release profiles that depend on the thickness of the deposited
      coat, with t50 extended from 4.9 to 143.9 h. More importantly, released Lys
      possessed a high degree of biological activity during the course of release
      maintaining at least 72% of initial activity. CONCLUSIONS: Successful loading of
      Lys and extension of its release while maintaining a considerable degree of
      activity might make this formulation suitable for use with other active
      therapeutic proteins.

PMID- 26289207
TI  - Genome-wide association mapping reveals novel sources of resistance to northern
      corn leaf blight in maize.
AB  - BACKGROUND: Northern corn leaf blight (NCLB) caused by Exserohilum turcicum is a
      destructive disease in maize. Using host resistance to minimize the detrimental
      effects of NCLB on maize productivity is the most cost-effective and appealing
      disease management strategy. However, this requires the identification and use of
      stable resistance genes that are effective across different environments.
      RESULTS: We evaluated a diverse maize population comprised of 999 inbred lines
      across different environments for resistance to NCLB. To identify genomic regions
      associated with NCLB resistance in maize, a genome-wide association analysis was
      conducted using 56,110 single-nucleotide polymorphism markers. Single-marker and
      haplotype-based associations, as well as Anderson-Darling tests, identified
      alleles significantly associated with NCLB resistance. The single-marker and
      haplotype-based association mappings identified twelve and ten loci (genes),
      respectively, that were significantly associated with resistance to NCLB.
      Additionally, by dividing the population into three subgroups and performing
      Anderson-Darling tests, eighty one genes were detected, and twelve of them were
      related to plant defense. Identical defense genes were identified using the three
      analyses. CONCLUSION: An association panel including 999 diverse lines was
      evaluated for resistance to NCLB in multiple environments, and a large number of
      resistant lines were identified and can be used as reliable resistance resource
      in maize breeding program. Genome-wide association study reveals that NCLB
      resistance is a complex trait which is under the control of many minor genes with
      relatively low effects. Pyramiding these genes in the same background is likely
      to result in stable resistance to NCLB.

PMID- 26289210
TI  - Synthesis, characterization and evaluation of tinidazole-loaded mPEG-PDLLA
      (10/90) in situ gel forming system for periodontitis treatment.
AB  - Traditional in situ gel forming systems are potential applications for parenteral
      administration but always accompanied with burst release. To overcome this
      limitation, the tinidazole (TNZ)-loaded in situ gel forming system using a
      diblock copolymer, monomethoxy poly(ethylene glycol)-block-poly(d,l-lactide)
      (mPEG-PDLLA), was designed. The formulation of the mPEG-PDLLA-based TNZ in situ
      gel forming system contained 5% (w/w) TNZ, 0.4% glycerol, 5 ml N-methyl
      pyrrolidone (NMP) and 35% (w/w) mPEG-PDLLA. The in situ gel forming system showed
      sustained TNZ release over 192 h with low burst effect (around 7% in the first 8
      h) in the in vitro release study. Additionally, in vivo studies were performed on
      rabbits with ligature-induced periodontitis, and the concentration of TNZ in the
      gingival crevicular fluid (GCF) as well as the pharmacokinetic parameters was
      calculated and the pharmacological effect of TNZ-loaded in situ gel forming (mPEG
      PDLLA)-based system was found effective. Finally, histological studies revealed
      that the gel was a safe formulation with low irritation. The desirable drug
      release kinetics combined with the excellent in vivo characteristics highlight
      the potential of the gel in the treatment of periodontitis. Therefore, these
      results confirmed that the TNZ-loaded in situ gel forming mPEG-PDLLA-based system
      could reduce burst release of TNZ and act as a sustained-release and injectable
      drug depot for periodontitis treatment.

PMID- 26289211
TI  - Transdermal delivery of tadalafil using a novel formulation.
AB  - The aim of this work was to investigate the transdermal gel loaded with
      tadalafil, a practically insoluble selective phosphodiesterase-5 inhibitor (PDE5)
      in order to improve the solubility and bioavailability. The solubility of
      tadalafil in mixed solution of hydroxypropyl-beta-cyclodextrin (HPCD),
      polyethylene glycol (PEG) 400 and tween 80 (T2 solution) was 260.8 +/- 4.3 ug/mL
      and that of tadalafil in modified T2 (M-T2) solution, which tadalafil was
      dissolved in 20% (w/v) HPCD at first and then mixture solutions of PEG 400 and
      tween 80 were added, was increased to 344.9 +/- 30.6 ug/mL. Four gel formulae
      were prepared, subsequently in vitro and in vivo skin permeation studies were
      carried out. Interestingly, tadalafil gel in M-T2 and oleic acid (OA) (F3) could
      promote the percutaneous absorption of tadalafil by 179.4% in vitro and increase
      AUC by 223% in vivo compared with tadalafil gel in the absence of M-T2 and OA
      (F1). Also, there was a finding that tadalafil gel in M-T2 and OA did not cause
      dermal irritations in an experimental animal. 

PMID- 26289212
TI  - Advances in nanotechnology-based carrier systems for targeted delivery of
      bioactive drug molecules with special emphasis on immunotherapy in drug resistant
      tuberculosis - a critical review.
AB  - From the early sixteenth and seventeenth centuries to the present day of life,
      tuberculosis (TB) still is a global health threat with some new emergence of
      resistance. This type of emergence poses a vital challenge to control TB cases
      across the world. Mortality and morbidity rates are high due to this new face of
      TB. The newer nanotechnology-based drug-delivery approaches involving micro
      metric and nano-metric carriers are much needed at this stage. These delivery
      systems would provide more advantages over conventional systems of treatment by
      producing enhanced therapeutic efficacy, uniform distribution of drug molecule to
      the target site, sustained and controlled release of drug molecules and lesser
      side effects. The main aim to develop these novel drug-delivery systems is to
      improve the patient compliance and reduce therapy time. This article reviews and
      elaborates the new concepts and drug-delivery approaches for the treatment of TB
      involving solid-lipid particulate drug-delivery systems (solid-lipid micro- and
      nanoparticles, nanostructured lipid carriers), vesicular drug-delivery systems
      (liposomes, niosomes and liposphere), emulsion-based drug-delivery systems (micro
      and nanoemulsion) and some other novel drug-delivery systems for the effective
      treatment of tuberculosis and role of immunomodulators as an adjuvant therapy for
      management of MDR-TB and XDR-TB. 

PMID- 26289213
TI  - The application of antitumor drug-targeting models on liver cancer.
AB  - Hepatocarcinoma animal models, such as the induced tumor model, transplanted
      tumor model, gene animal model, are significant experimental tools for the
      evaluation of targeting drug delivery system as well as the pre-clinical studies
      of liver cancer. The application of antitumor drug-targeting models not only
      furnishes similar biological characteristics to human liver cancer but also
      offers guarantee of pharmacokinetic indicators of the liver-targeting
      preparations. In this article, we have reviewed some kinds of antitumor drug
      targeting models of hepatoma and speculated that the research on this field would
      be capable of attaining a deeper level and expecting a superior achievement in
      the future. 

PMID- 26289214
TI  - A new peptide ligand for colon cancer targeted delivery of micelles.
AB  - Ligands are an imperative part of targeted drug delivery systems, and choosing a
      ligand with high affinity is a subject of considerable interest. In this study,
      we first synthesized a 12-residue peptide (TK) that interacts with integrin
      alpha6beta1 overexpressed on colonic cancer cells. The molecular binding affinity
      assay indicated that TK had a high binding affinity for integrin alpha6beta1. The
      results of cellular and tumor spheroid uptake suggested that TK peptide not only
      increases Caco-2 cells uptake, but also effectively increases penetration of the
      tumor spheroids. TK-conjugated PEG-PLA was synthesized to prepare a novel PEG-PLA
      micelles loading DOX or coumarin-6 (TK-MS/DOX or TK-MS/C6). The obtained TK
      MS/DOX exhibited uniform, spherical shape with a size of 23.80 +/- 0.32 nm and
      zeta potential of 12.21 +/- 0.31 mV. The release behavior of DOX from micelles
      were observed no significant changes after TK modification, however, the release
      profile exhibited pH-sensitive properties. Compared with MS/DOX, TK-MS/DOX
      exhibited significantly stronger cytotoxicity for Caco-2. Confocal laser
      microscopy and flow cytometry data further indicated that the targeting micelles
      not only had higher uptake by Caco-2 cells, but also more effectively penetrated
      the tumor spheroids. Therefore, TK peptide appears to be suitable as a targeting
      ligand with potential applications in colonic targeted therapy. 

PMID- 26289215
TI  - Intraocular distribution of topically applied hydrophilic and lipophilic
      substances in rat eyes.
AB  - PURPOSE: Topical administration is the preferred route of drug delivery for
      ophthalmic ailments. However, poor permeation through ocular surface and
      significant systemic absorption, makes the topical drug delivery challenging.
      Furthermore, distribution of topically delivered drugs varies with their
      physicochemical properties and the type of formulation used. Hence, this study
      was done to understand the pattern of ocular drug distribution of topically
      applied hydrophilic and lipophilic substances in two different formulations.
      METHODS: 5-Carboxyfluorescein and 1,1'-dioctadecyl-3,3,3',3'
      tetramethylindocarbocyanine perchlorate were used as representative candidates
      for hydrophilic and lipophilic substances, respectively. They were formulated in
      solution and liposomes. Single drop of either formulation containing hydrophilic
      or lipophilic substance was instilled topically, unilaterally to rat eyes.
      Subsequently, rats were sacrificed at 10, 30 and 120 min post-instillation. Eyes
      were cryosectioned and examined under confocal microscope to determine the
      fluorescence intensity in ocular tissues. RESULTS: Corneal permeation of
      hydrophilic and lipophilic substances in both formulations peaked at 30 min post
      instillation. Liposomal-lipophilic dye and non-liposomal-hydrophilic dye showed
      better corneal distribution. Fluorescence was absent in contralateral eyes of non
      liposomal-hydrophilic dye-treated animals but was present in contralateral eyes
      of liposomal-hydrophilic dye-treated animals. Fluorescence in contralateral eyes
      of liposomal-lipophilic dye-treated animals was significantly higher compared to
      non-liposomal-lipophilic dye-treated animals. CONCLUSIONS: Topically applied
      liposomal formulation of lipophilic substance provides higher corneal
      concentration of drug with lesser systemic absorption compared to its solution.
      For hydrophilic substance, topical use of solution provides greater corneal
      concentration compared to liposomes which is more likely to be absorbed
      systemically.

PMID- 26289216
TI  - Ultrasound-responsive nanobubbles contained with peptide-camptothecin conjugates
      for targeted drug delivery.
AB  - To improve the targeting delivery efficiency of anticancer drug to tumor sites, a
      new strategy combining cell-permeable peptide (CPP) and ultrasound was reported
      in this article. In this study, we devised and tested a strategy for functional
      payload delivery to cells by loading CPP-camptothecin conjugate (CPP-CPT) into
      nanobubble (CPP-CPT NB). Here, CPP existing in the conjugation form of CPP and
      CPT was hidden in nanobubble to cloak the penetration activity of CPP. Meanwhile,
      local tumor ultrasound was utilized to achieve specific targeting of CPP-CPT to
      the tumor cells. The mean particle size of the prepared CPP-CPT NB was ~200 nm,
      and the drug entrapment efficiency was >80%. Stimulated by ultrasound, over 90%
      of the entrapped CPP-CPTs would release from the nanobubbles. Subsequent research
      demonstrated that the CPP-CPT NB showed effective cellular uptake and significant
      cytotoxic activity in HeLa cells in vitro. Additionally, after systemic
      administration in mice, CPP-CPT NB with ultrasound showed a higher tumor
      inhibition effect in nude mice xenografted HeLa cells tumors and excellent body
      safety when compared with normal CPT injection group. In conclusion, the carrier
      constructed in this study would be a safe and efficiently drug delivery system
      for specific cancer treatment.

PMID- 26289218
TI  - A meta-analysis of the diagnostic accuracy of dengue virus-specific IgA antibody
      based tests for detection of dengue infection.
AB  - Immunoglobulin A (IgA)-based tests have been evaluated in different studies for
      their utility in diagnosing dengue infections. In most of the studies, the
      results were inconclusive because of a small sample size. Hence, a meta-analysis
      involving nine studies with 2096 samples was performed to assess the diagnostic
      accuracy of IgA-based tests in diagnosing dengue infections. The analysis was
      conducted using Meta-Disc software. The results revealed that IgA-based tests had
      an overall sensitivity, specificity, diagnostic odds ratio, and positive and
      negative likelihood ratios of 73.9%, 95.2%, 66.7, 22.0 and 0.25, respectively.
      Significant heterogeneity was observed between the studies. The type of test,
      infection status and day of sample collection influenced the diagnostic accuracy.
      The IgA-based diagnostic tests showed a greater accuracy when the samples were
      collected 4 days after onset of symptoms and for secondary infections. The
      results suggested that IgA-based tests had a moderate level of accuracy and are
      diagnostic of the disease. However, negative results cannot be used alone for
      dengue diagnosis. More prospective studies comparing the diagnostic accuracy of
      combinations of antigen-based tests with either IgA or IgM are needed and might
      be useful for suggesting the best strategy for dengue diagnosis. 

PMID- 26289219
TI  - Synthesis and characterisation of a pH-sensitive magnetic nanocomposite for
      controlled delivery of doxorubicin.
AB  - We prepared a magnetic chitosan-cis-aconitic anhydride-doxorubicin nanocomposite,
      denoted by MCS-CAA-DOX. Chitosan (CS) was linked to magnetic nanoparticles
      (Fe3O4) to decrease cytotoxicity of the composite and provided a large number of
      reactive sites for coupling of drug molecules. DOX was attached to the magnetic
      chitosan (MCS) via a pH-sensitive linker, cis-aconitic anhydride, which
      hydrolyses in the acidic lysosomal environment to allow pH-responsive release of
      DOX. The prepared nanocomposites were within 15 nm and had good superparamagnetic
      properties. The loading rate of DOX was up to 83%. It was found that nearly 88%
      DOX was released within 60 h at pH 5.0, compared with only 29% at pH 7.4. 

PMID- 26289217
TI  - Next-generation prognostic assessment for diffuse large B-cell lymphoma.
AB  - Current standard of care therapy for diffuse large B-cell lymphoma (DLBCL) cures
      a majority of patients with additional benefit in salvage therapy and autologous
      stem cell transplant for patients who relapse. The next generation of prognostic
      models for DLBCL aims to more accurately stratify patients for novel therapies
      and risk-adapted treatment strategies. This review discusses the significance of
      host genetic and tumor genomic alterations seen in DLBCL, clinical and
      epidemiologic factors, and how each can be integrated into risk stratification
      algorithms. In the future, treatment prediction and prognostic model development
      and subsequent validation will require data from a large number of DLBCL patients
      to establish sufficient statistical power to correctly predict outcome. Novel
      modeling approaches can augment these efforts. 

PMID- 26289221
TI  - Prediction of treatment outcomes in major depressive disorder.
AB  - Improving the treatment of major depressive disorder will require identification
      of moderators that predict differential outcomes across treatments at the level
      of the individual patient, referred to as precision medicine. Currently, there
      are no biological measures demonstrated to enhance treatment selection accuracy
      although there are some clinical variables that have prognostic value. Several
      recent studies comparing treatments with differing mechanisms of action have
      identified potential moderators that may eventually be used in precision medicine
      approaches. Genetic combination tests, systemic inflammation,
      electroencephalography and neuroimaging, in particular, show significant
      potential for near-term development as clinically meaningful moderators for use
      in treatment selection. Ultimately, combinations of moderators may provide the
      greatest level of precision in selecting optimal treatment approaches for
      individual depressed patients. 

PMID- 26289220
TI  - Enzymatic passaging of human embryonic stem cells alters central carbon
      metabolism and glycan abundance.
AB  - To realize the potential of human embryonic stem cells (hESCs) in regenerative
      medicine and drug discovery applications, large numbers of cells that accurately
      recapitulate cell and tissue function must be robustly produced. Previous studies
      have suggested that genetic instability and epigenetic changes occur as a
      consequence of enzymatic passaging. However, the potential impacts of such
      passaging methods on the metabolism of hESCs have not been described. Using
      stable isotope tracing and mass spectrometry-based metabolomics, we have explored
      how different passaging reagents impact hESC metabolism. Enzymatic passaging
      caused significant decreases in glucose utilization throughout central carbon
      metabolism along with attenuated de novo lipogenesis. In addition, we developed
      and validated a method for rapidly quantifying glycan abundance and isotopic
      labeling in hydrolyzed biomass. Enzymatic passaging reagents significantly
      altered levels of glycans immediately after digestion but surprisingly glucose
      contribution to glycans was not affected. These results demonstrate that there is
      an immediate effect on hESC metabolism after enzymatic passaging in both central
      carbon metabolism and biosynthesis. HESCs subjected to enzymatic passaging are
      routinely placed in a state requiring re-synthesis of biomass components, subtly
      influencing their metabolic needs in a manner that may impact cell performance in
      regenerative medicine applications. 

PMID- 26289222
TI  - How to use vancomycin optimally in neonates: remaining questions.
AB  - In neonates, vancomycin, a narrow-spectrum antibiotic, is the first choice of
      treatment of late-onset sepsis predominantly caused by Gram-positive bacteria
      (coagulase-negative staphylococci and enterococci). Although it has been used for
      >50 years, prescribing the right dose and dosing regimen remains a challenge in
      neonatal intensive care units for many reasons including high pharmacokinetic
      variability, increase in the minimal inhibition concentration against
      staphylococci, lack of consensus on dosing regimen and way of administration
      (continuous or intermittent), duration of treatment, use of therapeutic drug
      monitoring, limited data on short- and long-term toxicity, risk of mutant
      selection and errors of administration linked to concentrated formulations. This
      article highlights and discusses future research directions, with specific
      attention given to dosing optimization of vancomycin, including the advantages of
      modeling and simulation approaches. 

PMID- 26289223
TI  - What does the pharmacological future of treating chronic hepatitis C look like?
AB  - Development of direct acting antivirals has revolutionized the standard of care
      for the treatment of hepatitis C virus. New interferon-free regimens provide
      sustained virologic response rates of >90% in many genotype 1 patients with only
      12 weeks of oral therapy. This review will provide a brief overview of current
      standards of care with a summary of the evidence supporting the recommended
      combinations of direct acting antivirals. We will discuss the direction of future
      therapies, with strategies for shorter durations of therapy and new all-oral
      combinations in the pipeline. 

PMID- 26289224
TI  - Pharmacologic options for the treatment and management of food allergy.
AB  - Food allergy affects approximately 5% of adults and 8% of children in developed
      countries, and there is currently no cure. Current pharmacologic management is
      limited to using intramuscular epinephrine or oral antihistamines in response to
      food allergen exposure. Recent trials have examined the efficacy and safety of
      subcutaneous, oral, sublingual, and epicutaneous immunotherapy, with varying
      levels of efficacy and safety demonstrated. Bacterial adjuvants, use of anti-IgE
      monoclonal antibodies, and Chinese herbal formulations represent exciting
      potential for development of future pharmacotherapeutic agents. Ultimately,
      immunotherapy may be a viable option for patients with food allergy, although
      efficacy and safety are likely to be less than ideal. 

PMID- 26289225
TI  - Conbercept (KH-902) for the treatment of neovascular age-related macular
      degeneration.
AB  - Age-related macular degeneration (AMD) is a progressive, degenerative disease of
      the retina that occurs with increasing incidence with age and ranks third among
      the global causes of visual impairment. VEGF has been implicated in the
      development and progression of neovascular AMD. Drugs that block VEGF, leading to
      regression of the abnormal blood vessels, are the mainstay of treatment of
      neovascular AMD, particularly for subfoveal neovascular lesions. Anti-VEGF agents
      currently in use in neovascular AMD are pegaptanib (Macugen((r))), ranibizumab
      (Lucentis((r))), bevacizumab (Avastin((r))) and a soluble VEGF receptor decoy
      aflibercept (Eylea((r))). Recently, China Food and Drug Administration have
      approved conbercept for the treatment of neovascular AMD in China. Conbercept
      appears to offer yet another anti-VEGF drug for use in neovascular AMD. However,
      there is still a need for large, well-designed, randomized clinical trials to
      ensure its safety and efficacy. 

PMID- 26289226
TI  - Key findings from studies of methotrexate tapering and withdrawal in rheumatoid
      arthritis.
AB  - Methotrexate is the dominant initial drug in the management of rheumatoid
      arthritis (RA). Despite its widespread use, methotrexate is associated with a
      number of adverse effects. Tapering its dose to the minimal amount required to
      maintain RA remission is, therefore, an important clinical goal. While the
      complete withdrawal of disease-modifying anti-rheumatic drugs is associated with
      a definite risk of a disease flare, it is unclear as to what the risk is specific
      to methotrexate withdrawal and whether this can be minimized by gradual dose
      reduction (termed 'tapering'). This review examines studies of methotrexate
      tapering and withdrawal on RA outcomes. It covers three scenarios:
      tapering/withdrawing methotrexate monotherapy; tapering/withdrawing methotrexate
      as part of a 'step-down' combination disease-modifying anti-rheumatic drug
      regimen; and tapering/withdrawing methotrexate when it is being co-prescribed
      with biologic agents. 

PMID- 26289227
TI  - Enhancement of electrode performance by a simple casting method using
      sonochemically exfoliated graphene.
AB  - We demonstrate within this paper a method for modifying commercial screen-printed
      electrodes with aqueous graphene suspensions to enhance their electrochemical
      activity. The graphene suspensions are synthesized by a simple ultrasonic
      exfoliation method from graphite, where reaggregation is prevented by the
      addition of common cationic or anionic surfactants, thereby avoiding the use of
      organic solvents or harsh chemical procedures. These suspensions can then be
      simply cast onto the screen-printed electrodes. Cyclic voltammetry with a number
      of redox active species such as phenols, as well as impedance measurements, were
      made to characterize these systems. The modified electrodes are shown to
      demonstrate significantly enhanced electrochemical activity and greatly lowered
      electron transfer resistances compared to the unmodified electrodes. Initial
      proof of concept applications of these electrodes, including the detection of
      heavy metals by absorptive stripping voltammetry, are also shown. 

PMID- 26289229
TI  - Activation of aqueous hydrogen peroxide for non-catalyzed dihydroperoxidation of
      ketones by azeotropic removal of water.
AB  - Cyclic and acyclic ketones were selectively converted to gem-dihydroperoxides in
      72-99% yield with 30% aq. hydrogen peroxide by azeotropic distillation of water
      from the reaction mixture without any catalyst. The reactions were more selective
      than with 100% H2O2 and due to neutral conditions also less stable products could
      be obtained. 

PMID- 26289228
TI  - Prioritizing Parental Worry Associated with Duchenne Muscular Dystrophy Using
      Best-Worst Scaling.
AB  - Duchenne muscular dystrophy (DMD) is a progressive, fatal pediatric disorder with
      significant burden on parents. Assessing disease impact can inform clinical
      interventions. Best-worst scaling (BWS) was used to elicit parental priorities
      among 16 short-term, DMD-related worries identified through community engagement.
      Respondents viewed 16 subsets of worries, identified using a balanced, incomplete
      block design, and identified the most and least worrying items. Priorities were
      assessed using best-worst scores (spanning +1 to -1) representing the relative
      number of times items were endorsed as most and least worrying. Independent
      sample t-tests compared prioritization of parents with ambulatory and non
      ambulatory children. Participants (n = 119) most prioritized worries about
      weakness progression (BW score = 0.64) and getting the right care over time (BW =
      0.25). Compared to parents of non-ambulatory children, parents of ambulatory
      children more highly prioritized missing treatments (BW = 0.31 vs. 0.13, p <
      0.001) and being a good enough parent (BW = 0.06 vs. -0.08, p = 0.010), and less
      prioritized child feeling like a burden (BW = -0.24 vs. -0.07, p < 0.001).
      Regardless of child's disease stage, caregiver interventions should address the
      emotional impact of caring for a child with a progressive, fatal disease. We
      demonstrate an accessible, clinically-relevant approach to prioritize disease
      impact using BWS, which offers an alternative to the use of traditional
      rating/ranking scales.

PMID- 26289230
TI  - Efficacy of nasolabial flap in reconstruction of fibrotomy defect in surgical
      management of oral submucous fibrosis: a prospective study.
AB  - PURPOSE: Various surgical modalities have been used in the surgical management of
      oral submucous fibrosis with variable results. This prospective study evaluates
      the efficacy of nasolabial flap in the reconstruction of fibrotomy defect in
      surgical treatment of oral submucous fibrosis in terms of functional and esthetic
      outcomes. MATERIAL AND METHOD: In this prospective study, we treated 20 patients
      of oral submucous fibrosis surgically. The surgical protocol was consisting of
      bilateral fibrotomy, temporal myotomy, and coronoidotomy or coronoidectomy
      followed by reconstruction of fibrotomy defect with bilateral extended nasolabial
      flaps. All patients were prescribed with nutritional supplements and
      antioxidants. Vigorous mouth opening exercise was made compulsory for every
      patient. Preoperative and postoperative evaluation was done for interincisal
      mouth opening, function of mastication, and cosmetic results. Patient's regular
      follow-up was done for 2 years. RESULTS: Postoperatively, we noted excellent
      increase in the interincisal mouth opening relieving trismus. Patient's ability
      to chew solid food was increased significantly. Extraoral scar was minimal and
      well accepted by all the patients. There was no morbidity of the donor site.
      There was no injury to the facial nerve in all cases. The only drawback was
      intraoral hair growth which went on reducing with mucosalization of the graft
      tissue. CONCLUSION: Random pattern nasolabial flap is a very good option for
      intraoral reconstruction of fibrotomy defect in surgical treatment of oral
      submucous fibrosis with excellent functional and cosmetic results with minimal
      complications.

PMID- 26289231
TI  - A high-throughput acoustic cell sorter.
AB  - Acoustic-based fluorescence activated cell sorters (FACS) have drawn increased
      attention in recent years due to their versatility, high biocompatibility, high
      controllability, and simple design. However, the sorting throughput for existing
      acoustic cell sorters is far from optimum for practical applications. Here we
      report a high-throughput cell sorting method based on standing surface acoustic
      waves (SSAWs). We utilized a pair of focused interdigital transducers (FIDTs) to
      generate SSAW with high resolution and high energy efficiency. As a result, the
      sorting throughput is improved significantly from conventional acoustic-based
      cell sorting methods. We demonstrated the successful sorting of 10 MUm
      polystyrene particles with a minimum actuation time of 72 MUs, which translates
      to a potential sorting rate of more than 13,800 events per second. Without using
      a cell-detection unit, we were able to demonstrate an actual sorting throughput
      of 3300 events per second. Our sorting method can be conveniently integrated with
      upstream detection units, and it represents an important development towards a
      functional acoustic-based FACS system.

PMID- 26289233
TI  - Clinical Communities at Johns Hopkins Medicine: An Emerging Approach to Quality
      Improvement.
AB  - BACKGROUND: Clinical communities are an emerging approach to quality improvement
      (QI) to which several large-scale projects have attributed some success. In 2011
      the Armstrong Institute for Patient Safety and Quality established clinical
      communities as a core strategy to connect frontline providers from six different
      hospitals to improve quality of care, patient safety, and value across the health
      system. CLINICAL COMMUNITIES: Fourteen clinical communities that presented great
      opportunity for improvement were established. A community could focus on a
      clinical area, a patient population, a group, a process, a safety-related issue,
      or nearly any health care issue. The collaborative spirit of the communities
      embraced interdisciplinary membership and representation from each hospital in
      each community. Communities engaged in team-building activities and facilitated
      discussions, met monthly, and were encouraged to meet in person to develop
      relationships and build trust. After a community was established, patients and
      families were invited to join and share their perspectives and experiences.
      ENABLING STRUCTURES: The clinical community structure provided clinicians access
      to resources, such as technical experts and safety and QI researchers, that were
      not easily otherwise accessible or available. Communities convened clinicians
      from each hospital to consider safety problems and their resolution and share
      learning with workplace peers and local unit safety teams. CONCLUSION: The
      clinical communities engaged 195 clinicians from across the health system in QI
      projects and peer learning. Challenges included limited financial support and
      time for clinicians, timely access to data, limited resources from the health
      system, and not enough time with improvement experts.

PMID- 26289232
TI  - The effect of family and friend support on physical activity through adolescence:
      a longitudinal study.
AB  - BACKGROUND: This study examined if family and friend support predicted adolescent
      physical activity (PA) across a five-year time span. METHODS: The Iowa Bone
      Development Study collected objective measures of physical activity and self
      report of physical activity psychosocial factors at ages 13 (n = 306), 15 (n =
      356), and 17 yr (n = 317). Total moderate and vigorous-intensity PA (MVPA) and
      MVPA after 3 pm on weekdays (MVPA-PM Weekday) were measured using ActiGraph
      accelerometers. Family Support for PA and Friend Support for PA scales were
      measured using the Choices questionnaire. Models were adjusted for SES (mother's
      education) and somatic maturity (Mirwald predictive equations for maturity
      offset). Spearman correlation coefficients examined tracking of scales at ages
      13, 15 and 17. Logistic regression estimated the odds ratio for being in the
      lowest tertile of each scale at age 17 if in the lowest tertile at age 13. Linear
      mixed regression models investigated associations between these scales and MVPA
      outcomes over time. RESULTS: Two- and five-year intra-variable tracking
      associations for Family Support and Friend Support scales were moderate (r = 0.32
      0.58), except for the comparison between age 13 and age 17 Friend Support for
      girls, which resulted in a low association (r = 0.26). Boys and girls in the
      lowest tertile for support at age 13 were more likely to remain in the lowest
      tertile at age 17 compared to those in the middle and upper tertiles. The
      regression models indicated that when all other factors were held constant, an
      increase in family and/or friend support resulted in an increase in both MVPA
      outcomes CONCLUSIONS: From early to late adolescence, support for PA from the
      family and/or support from friends results in higher levels of total and
      discretionary MVPA. However, the importance of support in predicting MVPA
      decreased with age.

PMID- 26289234
TI  - A Novel Design for Drug-Drug Interaction Alerts Improves Prescribing Efficiency.
AB  - BACKGROUND: Drug-drug interactions (DDIs) are common in clinical care and pose
      serious risks for patients. Electronic health records display DDI alerts that can
      influence prescribers, but the interface design of DDI alerts has largely been
      unstudied. In this study, the objective was to apply human factors engineering
      principles to alert design. It was hypothesized that redesigned DDI alerts would
      significantly improve prescribers' efficiency and reduce prescribing errors.
      METHODS: In a counterbalanced, crossover study with prescribers, two DDI alert
      designs were evaluated. Department of Veterans Affairs (VA) prescribers were
      video recorded as they completed fictitious patient scenarios, which included DDI
      alerts of varying severity. Efficiency was measured from time-stamped recordings.
      Prescribing errors were evaluated against predefined criteria. Efficiency and
      prescribing errors were analyzed with the Wilcoxon signed-rank test. Other
      usability data were collected on the adequacy of alert content, prescribers' use
      of the DDI monograph, and alert navigation. RESULTS: Twenty prescribers completed
      patient scenarios for both designs. Prescribers resolved redesigned alerts in
      about half the time (redesign: 52 seconds versus original design: 97 seconds;
      p<.001). Prescribing errors were not significantly different between the two
      designs. Usability results indicate that DDI alerts might be enhanced by
      facilitating easier access to laboratory data and dosing information and by
      allowing prescribers to cancel either interacting medication directly from the
      alert. Results also suggest that neither design provided adequate information for
      decision making via the primary interface. CONCLUSION: Applying human factors
      principles to DDI alerts improved overall efficiency. Aspects of DDI alert design
      that could be further enhanced prior to implementation were also identified.

PMID- 26289235
TI  - Experience with Designing and Implementing a Bundled Payment Program for Total
      Hip Replacement.
AB  - BACKGROUND: Bundled payments, also known as episode-based payments, are intended
      to contain health care costs and promote quality. In 2011 a bundled payment pilot
      program for total hip replacement was implemented by an integrated health care
      delivery system in conjunction with a commercial health plan subsidiary. In July
      2015 the Centers for Medicare & Medicaid Services (CMS) proposed the
      Comprehensive Care for Joint Replacement Model to test bundled payment for hip
      and knee replacement. METHODS: Stakeholders were identified and a structure for
      program development and implementation was created. An Oversight Committee
      provided governance over a Clinical Model Subgroup and a Financial Model
      Subgroup. RESULTS: The pilot program included (1) a clinical model of care
      encompassing the period from the preoperative evaluation through the third
      postoperative visit, (2) a pricing model, (3) a program to share savings, and (4)
      a patient engagement and expectation strategy. Compared to 32 historical controls
      patients treated before bundle implementation-45 post-bundle-implementation
      patients with total hip replacement had a similar length of hospital stay (3.0
      versus 3.4 days, p=.24), higher rates of discharge to home or home with services
      than to a rehabilitation facility (87% versus 63%), similar adjusted median total
      payments ($22,272 versus $22,567, p=.43), and lower median posthospital payments
      ($704 versus $1,121, p=.002), and were more likely to receive guideline
      consistent care (99% versus 95%, p=.05). DISCUSSION: The bundled payment pilot
      program was associated with similar total costs, decreased posthospital costs,
      fewer discharges to rehabilitation facilities, and improved quality. Successful
      implementation of the program hinged on buy-in from stakeholders and close
      collaboration between stakeholders and the clinical and financial teams.

PMID- 26289236
TI  - Effect of a Real-Time Pediatric ICU Safety Bundle Dashboard on Quality
      Improvement Measures.
AB  - BACKGROUND: Patient daily goal sheets have been shown to improve compliance with
      hospital policies but might not represent the dynamic nature of care delivery in
      the pediatric ICU (PICU) setting. A study was conducted at Children's National
      Health System (Washington, DC) to determine the effect of a visible, unitwide,
      real-time dashboard on timeliness of compliance with quality and safety measures.
      METHODS: An automated electronic health record (EHR)- querying tool was created
      to assess compliance with a PICU Safety Bundle. Querying of the EHR for
      compliance and updating of the dashboard automatically occurred every five
      minutes. A real-time visual display showed data on presence of consent for
      treatment, restraint orders, presence of urinary catheters, deep venous
      thrombosis (DVT) prophylaxis, Braden Q score, and medication reconciliation.
      Baseline compliance and duration of noncompliance was established during three
      time periods: the first, before activation of the dashboard; the second, at one
      month following activation of the dashboard; and the third, at three months after
      activation. RESULTS: A total of 450 patients were included in the analysis.
      Between the first and third time periods, the median time from PICU admission to
      obtaining treatment consent decreased by 49%, from 393 to 202 minutes (p=.05).
      The number of patients with urinary catheters in place>96 hours decreased from 16
      (32%) in Period 1 to 11 (19%) for Periods 2 and 3 combined (p=.01). Completion of
      medication reconciliation improved from 80% in the first time period to 93% and
      92%, respectively, in the subsequent two periods (p=.002). There was no
      difference between the three periods in presence of restraint orders, DVT
      prophylaxis, or development or worsening of pressure ulcers. CONCLUSIONS: A
      unitwide dashboard can increase awareness for potential interventions, affecting
      patient safety in the PICU in a dynamic manner.

PMID- 26289237
TI  - Rapidly Increasing Rapid Response Team Activation Rates.

PMID- 26289238
TI  - Using Multidisciplinary Rounds to Improve Patient Safety Through Venous
      Thromboembolism Prevention Awareness.

PMID- 26289239
TI  - [Underlying Mechanisms and Management of Refractory Gastroesophageal Reflux
      Disease].
AB  - The prevalence of gastroesophageal reflux disease (GERD) in South Korea has
      increased over the past 10 years. Patients with erosive reflux disease (ERD)
      shows better response to proton pump inhibitors (PPIs) than those with non
      erosive reflux disease (NERD). NERD is a heterogeneous condition, showing
      pathological gastroesophageal reflux or esophageal hypersensitivity to reflux
      contents. NERD patients with pathological gastroesophageal reflux or
      hypersensitivity to acid may respond to PPIs. However, many patients with
      esophageal hypersensitivity to nonacid or functional heartburn do not respond to
      PPIs. Therefore, careful history and investigations are required when managing
      patients with refractory GERD who show poor response to conventional dose PPIs.
      Combined pH-impedance studies and a PPI diagnostic trial are recommended to
      reveal underlying mechanisms of refractory symptoms. For those with ongoing
      reflux-related symptoms, split dose administration, change to long-acting PPIs or
      PPIs less influenced by CYP2C19 genotypes, increasing dose of PPIs, and the
      addition of alginate preparations, prokinetics, selective serotonin reuptake
      inhibitors, or tricyclic antidepressants can be considered. Pain modulators,
      selective serotonin reuptake inhibitors, or tricyclic antidepressants are more
      likely to be effective for those with reflux-unrelated symptoms. Surgery or
      endoscopic per oral fundoplication may be effective in selected patients. 

PMID- 26289240
TI  - RUNX3 Methylation, Loss of RUNX3 Expression and Clinicopathologic Findings
      according to Helicobacter pylori CagA in Gastric Carcinoma.
AB  - BACKGROUND/AIMS: Helicobacter pylori cytotoxin-associated gene A (CagA) has been
      suggested to be involved in the inactivation of Runt-related transcription factor
      3 (RUNX3), a known gastric carcinoma tumor suppressor gene. It remains unclear
      how H. pylori CagA initiates or maintains RUNX3 promoter methylation and
      inactivates its protein expression in gastric carcinoma. METHODS: RUNX3 promoter
      methylation status, RUNX3 expression, and H. pylori CagA were investigated in 76
      sample pairs of gastric carcinoma tissue. The patients' medical records were
      reviewed. The association between RUNX3 methylation or loss of RUNX3 expression
      and clinicopathologic variables according to H. pylori CagA status were
      investigated. RESULTS: In gastric carcinoma patients with H. pylori CagA-positive
      infection, RUNX3 methylation did not show association with lymphatic invasion,
      venous invasion, and TNM stages. However RUNX3 methylation was observed more
      frequently in poorly differentiated adenocarcinoma and signet ring cell carcinoma
      (77.8% vs. 20.0%, p=0.023) in early stage. In gastric carcinoma patients with H.
      pylori CagA-positive infection, loss of RUNX3 expression did not show association
      with lymphatic invasion, venous invasion, and TNM stages. However loss of RUNX3
      expression was observed more frequently in early gastric carcinoma than in
      advanced gastric carcinoma (84.2% vs. 75.0%, p=0.51), but this difference was not
      significant. CONCLUSIONS: In gastric carcinoma patients with H. pylori CagA
      positive infection, RUNX3 methylation or loss of RUNX3 expression did not show
      correlation with lymphovascular invasion and TNM stages. In early gastric
      carcinoma patients with H. pylori CagA-positive infection, RUNX3 methylation was
      observed more in poorly differentiated adenocarcinoma and signet ring cell
      carcinoma.

PMID- 26289242
TI  - The Usefulness of Water-drinking Ultrasonography Combined Test for Evaluating
      Patients with Functional Dyspepsia.
AB  - BACKGROUND/AIMS: The major causes of functional dyspepsia (FD) are motility
      dysfunction and visceral hypersensitivity. Despite the large number of diagnostic
      tests, there are no convenient methods for evaluation of gastric functions.
      Therefore, this study was conducted to assess the relationship between the degree
      of dyspepsia and gastric accommodation, emptying, and sensitivity. METHODS: A
      total of 120 FD patients that met the Rome III criteria and 30 healthy volunteers
      were included in this cross-sectional study. The mean cross-sectional area of the
      fornix was measured to investigate fundic accommodation and gastric emptying
      during and after water intake. During the test, abdominal symptoms were evaluated
      using the 4-point Likert scale. RESULTS: The water-drinking ultrasonography
      combined test revealed impairment of gastric accommodation in FD after 1,000 mL
      of water intake, delayed emptying after 5 min of water intake and statistically
      significant hyperesthesia after 400 mL of water intake in the FD group compared
      with healthy controls (p <?? 0.05). Postprandial distress syndrome (PDS) and
      overlap syndrome were independently associated with gut motor disturbances
      instead of epigastric pain syndrome (EPS) (p <?? 0.01). CONCLUSIONS: The results
      of the present study suggest that the water-drinking ultrasonography combined
      test could be used for diagnosis of gastric motor and sensory dysfunction,
      particularly in PDS and EPS-PDS patients. This test is easy, well tolerated by
      the patient and can be widely applied in clinical practice.

PMID- 26289241
TI  - [Comparison on Endoscopic Hemoclip and Hemoclip Combination Therapy in Non
      variceal Upper Gastrointestinal Bleeding Patients Based on Clinical Practice
      Data: Is There Difference between Prospective Cohort Study and Randomized
      Study?].
AB  - BACKGROUND/AIMS: Endoscopic hemoclip application is an effective and safe method
      of endoscopic hemostasis. We conducted a multicenter retrospective study on
      hemoclip and hemoclip combination therapy based on prospective cohort database in
      terms of hemostatic efficacy not in clinical trial but in real clinical practice.
      METHODS: Data on endoscopic hemostasis for non-variceal upper gastrointestinal
      bleeding (NVUGIB) were prospectively collected from February 2011 to December
      2013. Among 1,584 patients with NVUGIB, 186 patients treated with hemoclip were
      enrolled in this study. Subjects were divided into three groups: Group 1 (n =
      62), hemoclipping only; group 2 (n = 88), hemoclipping plus epinephrine
      injection; and group 3 (n = 36), hemocliping and epinephrine injection plus other
      endoscopic hemostatic modalities. Primary outcomes included rebleeding, other
      therapeutic management, hospitalization period, fasting period and mortality.
      Secondary outcomes were bleeding associated mortality and overall mortality.
      RESULTS: Active bleeding and peptic ulcer bleeding were more common in group 3
      than in group 1 and in group 2 (p <? 0.001). However, primary outcomes
      (rebleeding, other management, morbidity, hospitalization period, fasting period
      and mortality) and secondary outcomes (bleeding associated mortality and total
      mortality) were not different among groups. CONCLUSIONS: Combination therapy of
      epinephrine injection and other modalities with hemoclips did not show advantage
      over hemoclipping alone in this prospective cohort study. However, there is a
      tendency to perform combination therapy in active bleeding which resulted in
      equivalent hemostatic success rate, and this reflects the role of combination
      therapy in clinical practice.

PMID- 26289243
TI  - [Comparison between Endoscopic Therapy and Medical Therapy in Peptic Ulcer
      Patients with Adherent Clot: A Multicenter Prospective Observational Cohort
      Study].
AB  - BACKGROUND/AIMS: The optimal management of bleeding peptic ulcer with adherent
      clot remains controversial. The purpose of this study was to compare clinical
      outcome between endoscopic therapy and medical therapy. We also evaluated the
      risk factors of rebleeding in Forrest type IIB peptic ulcer. METHODS: Upper
      gastrointestinal (UGI) bleeding registry data from 8 hospitals in Korea between
      February 2011 and December 2013 were reviewed and categorized according to the
      Forrest classification. Patients with acute UGI bleeding from peptic ulcer with
      adherent clots were enrolled. RESULTS: Among a total of 1,101 patients diagnosed
      with peptic ulcer bleeding, 126 bleedings (11.4%) were classified as Forrest type
      IIB. Of the 126 patients with adherent clots, 84 (66.7%) received endoscopic
      therapy and 42 (33.3%) were managed with medical therapy alone. The baseline
      characteristics of patients in two groups were similar except for higher Glasgow
      Blatchford Score and pre-endoscopic Rockall score in medical therapy group.
      Bleeding related mortality (1.2% vs.10%; p=0.018) and all cause mortality (3.7%
      vs. 20.0%; p=0.005) were significantly lower in the endoscopic therapy group.
      However, there was no difference between endoscopic therapy and medical therapy
      regarding rebleeding (7.1% vs. 9.5%; p=0.641). In multivariate analysis,
      independent risk factors of rebleeding were previous medication with aspirin
      and/or NSAID (OR, 13.1; p=0.025). CONCLUSIONS: In patients with Forrest type IIB
      peptic ulcer bleeding, endoscopic therapy was associated with a significant
      reduction in bleeding related mortality and all cause mortality compared with
      medical therapy alone. Important risk factor of rebleeding was use of aspirin
      and/or NSAID.

PMID- 26289244
TI  - [Peutz-Jeghers Syndrome with Adenomatous Change in a Fifteen-month-old Boy].
AB  - Peutz-Jeghers syndrome (PJS) is a very rare genetic disorder. PJS carries a high
      risk of developing gastrointestinal (GI) cancer or non-GI cancer with advancing
      years. However, major symptoms of PJS in childhood are obstruction,
      intussusception, and bleeding from hamartomatous intestinal polyps which in
      majority of cases are not related to cancer. Generally, first GI symptom develops
      by 20 years in one half of children diagnosed with PJS. Children under two years
      of age who had PJS polyp-related intestinal symptoms are rare, and there have
      been no published report on intestinal carcinoma development, adenomatous change
      or dysplasia of polyps in Korean children with PJS. Recently, the authors have
      experienced a case PJS with adenomatous polyp change in a 15-month-old boy who
      had STK11 gene mutation. Therefore, early evaluation could be necessary and
      considered in children with PJS. 

PMID- 26289245
TI  - Diffuse Ganglioneuromatosis of the Colon Presenting as a Large Subepithelial
      Tumor in Adults: Report of Two Cases.
AB  - Colonic diffuse ganglioneuromatosis is a benign neoplastic condition
      characterized by disseminated, intramural, or transmural proliferation of neural
      elements involving the enteric plexuses, sometimes associated with von
      Recklinghausen's disease and other multiple tumor syndromes. Colonic diffuse
      ganglioneuromatosis is usually large, ranging from 1 to 17 cm, and thus can
      distort the surrounding tissue architecture as well as infiltrate the adjacent
      bowel wall. However, colonic diffuse ganglioneuromatosis is an exceptional
      finding in adults and only individual cases are reported in the literature.
      Herein, we report two unusual cases of adult patients with colonic diffuse
      transmural ganglioneuromatosis presenting as a large subepithelial tumor. 

PMID- 26289246
TI  - A Case of Leukemoid Reaction in Pancreatic Ductal Adenocarcinoma.
AB  - Leukemoid reaction is defined as leukocytosis exceeding 50,000 cells/mm(3). When
      it occurs in a patient with a malignancy, secondary causes such as infections,
      drugs, hematologic diseases and hemorrhage need to be ruled out. After excluding
      such causes, paraneoplastic leukemoid reaction can be considered as a diagnosis
      of exclusion. Paraneoplastic leukemoid reactions have been described in
      association with lung, gastrointestinal, genitourinary and head and neck cancers.
      However, pancreatic cancer with leukemoid reaction has been rarely reported. We
      diagnosed a case of a 55-year-old Korean woman with extreme leukocytosis
      associated with advanced pancreatic cancer. 

PMID- 26289247
TI  - Complete Tumor Resection for a Hepatocellular Carcinoma Secreting Parathyroid
      Hormone-related Peptide.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common cancer in Korea. Diverse
      paraneoplastic syndromes can occur in patients with HCC, but parathyroid hormone
      related peptide (PTH-rP)-induced hypercalcemia is uncommon. Hypercalcemia due to
      PTH or particularly PTH-rP-secreting HCC is associated with poor outcomes. We
      report a 71-year-old man who presented with symptoms of vague abdominal
      discomfort, somnolence, lethargy, nausea, vomiting, and weight loss. Imaging
      studies revealed a large HCC without metastasis. The laboratory findings showed
      elevated serum calcium level, low intact parathyroid hormone (iPTH) level and
      elevated PTH-rP level. These results led to a diagnosis of a PTH-rP-secreting HCC
      and paraneoplastic hypercalcemia. After emergency management of the
      hypercalcemia, the patient underwent an extended right hemihepatectomy with
      cholecystectomy. One year after the surgery, he is alive with normal calcium, PTH
      rP, and iPTH levels. This case demonstrates that the rare phenomenon of life
      threatening hypercalcemia caused by HCC should not be overlooked. These symptoms
      offer a good opportunity to diagnose HCC early. Radical tumor resection makes it
      possible to cure patients with PTH-rP-secreting HCC.

PMID- 26289248
TI  - Clinical Use of Cannabinoids for Symptom Control in Multiple Sclerosis.
AB  - The endocannabinoid system was discovered in 1988 but has received little
      attention for its potential therapeutic possibilities. That has started to
      change, and since 2000, a significant number of clinical trials of cannabinoids,
      principally for the control of spasticity in multiple sclerosis, have been
      undertaken. These studies have been difficult because of the nature of the
      disease and have involved patients for whom other therapies have failed or proved
      inadequate. This paper outlines the background to the use of cannabinoids
      available and discusses the principles of practice associated with their safe
      use. The focus has been on nabiximols, being the most studied and the only
      cannabinoid that has been both adequately researched for use in multiple
      sclerosis and granted a license by the regulators. However, what has emerged is
      that the effect for many patients can be much wider than just control of
      spasticity. Within and outside of neurology there seems to be an expanding range
      of possibilities for the therapeutic use of cannabinoids.

PMID- 26289249
TI  - Cardiomyogenic differentiation of human sternal bone marrow mesenchymal stem
      cells using a combination of basic fibroblast growth factor and hydrocortisone.
AB  - The alarming rate of increase in myocardial infarction and marginal success in
      efforts to regenerate the damaged myocardium through conventional treatments
      creates an exceptional avenue for cell-based therapy. Adult bone marrow
      mesenchymal stem cells (MSCs) can be differentiated into cardiomyocytes, by
      treatment with 5-azacytidine, thus, have been anticipated as a therapeutic tool
      for myocardial infarction treatment. In this study, we investigated the ability
      of basic fibroblastic growth factor (bFGF) and hydrocortisone as a combined
      treatment to stimulate the differentiation of MSCs into cardiomyocytes. MSCs were
      isolated from sternal marrow of patients undergoing heart surgery (CABG). The
      isolated cells were initially monitored for the growth pattern, followed by
      characterization using ISCT recommendations. Cells were then differentiated using
      a combination of bFGF and hydrocortisone and evaluated for the expression of
      characteristic cardiac markers such as CTnI, CTnC, and Cnx43 at protein level
      using immunocytochemistry and flow cytometry, and CTnC and CTnT at mRNA level.
      The expression levels and pattern of the cardiac markers upon analysis with ICC
      and qRT-PCR were similar to that of 5-azacytidine induced cells and cultured
      primary human cardiomyocytes. However, flow cytometric evaluation revealed that
      induction with bFGF and hydrocortisone drives MSC differentiation to
      cardiomyocytes with a marginally higher efficiency. These results indicate that
      combination treatment of bFGF and hydrocortisone can be used as an alternative
      induction method for cardiomyogenic differentiation of MSCs for future clinical
      applications.

PMID- 26289250
TI  - Fast determination of the (1)H relaxivities of MRI contrast agents.

PMID- 26289251
TI  - A physician survey reveals differences in management of idiopathic pulmonary
      hemosiderosis.
AB  - BACKGROUND: Idiopathic pulmonary hemosiderosis (IPH) is a rare disorder of
      unknown etiology characterized by chronic pulmonary hemorrhage and presents with
      a triad of anemia, hemoptysis and pulmonary infiltrates. IPH is a diagnosis of
      exclusion with a variable and disparate clinical course. Despite existing
      therapies, few children achieve full remission while others have recurrent
      hemorrhage, progressive lung damage, and premature death. METHODS: We surveyed
      physicians who care for patients with IPH via a web-based survey to assess the
      most common practices. 88 providers responded, caring for 274 IPH patients from
      five continents. RESULTS: 63.3 % of respondents had patients that were initially
      misdiagnosed with anemia (60.0 %) or gastrointestinal bleed (18.2 %). Respondents
      varied in diagnostic tools used for evaluation. The key difference was in the use
      of lung biopsy (51.9 %) for diagnosis. Common medications respondents used for
      treatment at initial presentation and chronic maintenance therapy were
      corticosteroids (98.7 and 84.0 %, initial and chronic therapy respectively),
      hydroxychloroquine (33.3 and 64.0 %), azathioprine (8.0 and 37.3 %), and
      cyclophosphamide (4.0 and 16.0 %). There was agreement on the use of
      corticosteroids for exacerbation amongst all respondents. Reported deaths before
      adulthood occurred in 7.3 % of patients. We conclude that there were common
      features and specific variations in physician management of IPH. Respondents were
      divided on whether to perform lung biopsy for diagnosis. CONCLUSION: Despite the
      availability of various immunomodulators, corticosteroids remained the primary
      therapy. We speculate that the standardization of care for diffuse alveolar
      hemorrhage will improve patient outcomes.

PMID- 26289253
TI  - Endothelial autophagy and Endothelial-to-Mesenchymal Transition (EndoMT) in eEPC
      treatment of ischemic AKI.
AB  - BACKGROUND: Autophagy enables cells to digest endogenous/exogenous waste
      products, thus potentially prolonging the cellular lifespan. Early endothelial
      progenitor cells (eEPCs) protect mice from ischemic acute kidney injury (AKI).
      The mid-term prognosis in AKI critically depends on vascular rarefication and
      interstitial fibrosis with the latter partly being induced by mesenchymal
      transdifferentiation of endothelial cells (EndoMT). This study aimed to determine
      the impact of eEPC preconditioning with different autophagy inducing agents
      [suberoylanilide hydroxamic acid (SAHA)/temsirolimus] in ischemic AKI. METHODS:
      Male C57/Bl6 N mice were subjected to bilateral renal ischemia (40 min). Animals
      were injected with either untreated, or SAHA- or temsirolimus-pretreated
      syngeneic murine eEPCs at the time of reperfusion. Mice were analyzed 48 h and 4
      weeks later. In addition, cultured eEPCs were treated with transforming growth
      factor (TGF)-beta +/- SAHA, autophagy (perinuclear LC3-II), and stress-induced
      premature senescence (SIPS-senescence-associated beta-galactosidase, SA-beta
      Gal), and were evaluated 96 h later. RESULTS: Cultured eEPCs showed reduced
      perinuclear density of LC3-II + vesicles and elevated levels of SA-beta-Gal after
      treatment with TGF-beta alone, indicating impaired autophagy and aggravated SIPS.
      These effects were completely abrogated by SAHA. Systemic administration of
      either SAHA or tems pretreated eEPCs resulted in elevated intrarenal endothelial
      p62 at 48 h and 4 weeks, indicating stimulated endothelial autophagy. This effect
      was most pronounced after injection of SAHA-treated eEPCs. At 4 weeks endothelial
      expression of mesenchymal alpha-smooth muscle actin (alphaSMA) was reduced in
      animals receiving untreated and SAHA-pretreated cells. In addition, SAHA-treated
      cells reduced fibrosis at week 4. Tems in contrast aggravated EndoMT.
      Postischemic renal function declined after renal ischemia and remained unaffected
      in all experimental cell treatment groups. CONCLUSION: In ischemic AKI,
      intrarenal endothelial autophagy may be stabilized by systemic administration of
      pharmacologically preconditioned eEPCs. Early EPCs can reduce postischemic EndoMT
      and fibrosis in the mid-term. Autophagy induction in eEPCs either increases or
      decreases the mesenchymal properties of intrarenal endothelial cells, depending
      on the substance being used. Thus, endothelial autophagy induction in ischemic
      AKI, mediated by eEPCs is not a renoprotective event per se.

PMID- 26289252
TI  - The role of adverse childhood experiences in cardiovascular disease risk: a
      review with emphasis on plausible mechanisms.
AB  - Childhood adversity, characterized by abuse, neglect, and household dysfunction,
      is a problem that exerts a significant impact on individuals, families, and
      society. Growing evidence suggests that adverse childhood experiences (ACEs) are
      associated with health decline in adulthood, including cardiovascular disease
      (CVD). In the current review, we first provide an overview of the association
      between ACEs and CVD risk, with updates on the latest epidemiological evidence.
      Second, we briefly review plausible pathways by which ACEs could influence CVD
      risk, including traditional risk factors and novel mechanisms. Finally, we
      highlight the potential implications of ACEs in clinical and public health.
      Information gleaned from this review should help physicians and researchers in
      better understanding potential long-term consequences of ACEs and considering
      adapting current strategies in treatment or intervention for patients with ACEs. 

PMID- 26289254
TI  - Gas density alters expiratory time constants before and after experimental lung
      injury.
AB  - NEW FINDINGS: What is the central question of this study? Does the induction of a
      model of lung injury affect the expiratory time constant (tauE) in terms of
      either total duration or morphology? Does ventilation with gases of different
      densities alter the duration or morphology of tauE either before or after injury?
      What is the main finding and its importance? The use of sulfur hexafluoride in
      ventilating gas mixtures lengthens total expiratory time constants before and
      after lung injury compared with both nitrogen and helium mixtures. Sulfur
      hexafluoride mixtures also decrease the difference and variability of tauE
      between fast- and slow-emptying compartments before and after injury when
      compared with nitrogen and helium mixtures. Acute lung injury is characterized by
      regional heterogeneity of lung resistance and elastance that may lead to regional
      heterogeneity of expiratory time constants (tauE). We hypothesized that
      increasing airflow resistance by using inhaled sulfur hexafluoride (SF6) would
      lengthen time constants and decrease their heterogeneity in an experimental model
      of lung injury when compared with nitrogen or helium mixtures. To overcome the
      limitations of a single-compartment model, we employed a multisegment model of
      expiratory gas flow. An experimental model of lung injury was created using
      intratracheal injection of sodium polyacrylate in anaesthetized and mechanically
      ventilated female Yorkshire-cross pigs (n = 7). The animals were ventilated with
      50% O2 and the remaining 50% as nitrogen (N2), helium (He) or sulfur hexafluoride
      (SF6). Values for tauE decreased with injury and were more variable after injury
      than before (P < 0.001). Values for tauE increased throughout expiration both
      before and after injury, and the rate of increase in tauE was lessened by SF6 (P
      < 0.001 when compared with N2 both before and after injury). Altering the inhaled
      gas density did not affect indices of oxygenation, dead space or shunt. The use
      of SF6 in ventilating gas mixtures lengthens total expiratory time constants
      before and after lung injury compared with both N2 and He mixtures. Importantly,
      SF6 mixtures also decrease the difference and variability of tauE between fast-
      and slow-emptying compartments before and after injury when compared with N2 and
      He mixtures.

PMID- 26289255
TI  - The Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors and
      Angiotensin II Receptor Blockers in Patients With Diabetes.
AB  - The evidence examining the effect of angiotensin-converting enzyme (ACE)
      inhibitors and angiotensin receptor blockers (ARBs) on mortality in high-risk
      patients is conflicting. To further examine this controversy, the authors
      compared outcomes between ACE inhibitors and ARBs in a large clinical diabetes
      registry. A retrospective cohort of 87,472 incident users followed for 105,702
      patient-years was analyzed. Average age was 53.1+/-10.1 years, 54.2% were men,
      and 14.4% had cardiovascular disease. All-cause hospitalization or all-cause
      mortality, the composite primary endpoint, occurred in 10,943 (12.5%) patients.
      Compared with ACE inhibitors, the adjusted hazard for ARBs was 0.90 (95%
      confidence interval, 0.87-0.94) for all-cause hospitalization or mortality; 0.95
      (0.65-1.40) for mortality; 0.90 (0.87-0.94) for all-cause hospitalization; and
      0.81 (0.74-0.89) for cardiovascular admission. ARB use was associated with a
      reduced, not increased, risk of hospitalization/mortality relative to ACE
      inhibition. This was driven by lower hospitalization, with a null mortality
      result.

PMID- 26289256
TI  - Frequent Use of Antibiotics Is Associated with Colorectal Cancer Risk: Results of
      a Nested Case-Control Study.
AB  - BACKGROUND: Microbiotical dysbiosis induced by a Western diet seems to be
      associated with an increased risk of developing colorectal cancer (CRC). Few
      other factors with an effect on the colonic microbiota and their association with
      CRC have been evaluated. AIM: We investigated whether the use of antibiotics is
      associated with CRC risk. METHODS: Data on the use of antibiotics and
      comedication were extracted from a health insurance database for subjects with a
      diagnostic-related group for CRC between 2006 and 2011 and four age- and sex
      matched controls. Antibiotic use was categorized according to the number of
      prescriptions during a 5-year follow-up period (1-6 years prior to CRC).
      Multivariable conditional binary logistic regression analysis was used to
      estimate odds ratios (ORs) and 95 % confidence intervals (95 % CIs) for different
      levels of use. RESULTS: A total of 4029 cases (47 % male, mean age at diagnosis
      71 +/- 11 years) and 15,988 controls were included. Antibiotics had been
      prescribed to 2630 (65.3 %) cases and 10,234 (64.0 %) controls (p = 0.13). An
      increasing use of antibiotics was associated with an increasing risk of CRC
      [multivariable OR for high (>=8 prescriptions) vs. no prescriptions: 1.26, 95 %
      CI 1.11-1.44, p-trend <0.01]. For each increase of 5 prescriptions, the OR for
      CRC was 1.05 (95 % CI 1.01-1.09). CONCLUSION: We found an association between the
      use of antibiotics, especially when used frequently, and the risk of developing
      CRC. Further studies are needed to establish under which conditions the use of
      antibiotics increases the risk of developing CRC.

PMID- 26289257
TI  - Outcomes of Next-Day Versus Non-next-Day Colonoscopy After an Initial Inadequate
      Bowel Preparation.
AB  - BACKGROUND: Inadequate bowel preparation is the most common cause of failed
      colonoscopy, and repeat failure occurs in more than 20 % of follow-up attempts.
      Limited data suggest that next-day follow-up may reduce the risk for repeat
      inadequate preparation. OBJECTIVE: Evaluate differences in prep quality with next
      day follow-up after initial inadequate preparation. DESIGN: Retrospective study.
      SETTING: Academic center. PATIENTS: Outpatient screening and surveillance
      colonoscopies between 7/2002 and 6/2007. INTERVENTION: Comparison of next-day
      versus any other day ("non-next-day") repeat colonoscopy outcomes. MAIN OUTCOME
      MEASUREMENTS: Aronchick scale, polyp and adenoma detection rates. RESULTS: Of
      20,798 initial colonoscopies, 857 (4.1 %) had inadequate preparation. 460 (54 %)
      were lost to follow-up. One hundred and fourteen (13 %) had next-day and 283 (33
      %) had non-next-day colonoscopy with mean follow-up of 8.8 months. On follow-up
      examination, 29.8 % of next-day and 23.3 % of non-next-day colonoscopies had
      inadequate bowel preparation (p = 0.48). The adenoma detection rate for the next
      day group improved from 3.5 to 38.6 % on follow-up, compared to 20.5 and 36.8 %
      in the non-next-day group. There was no significant difference between groups in
      detection of total adenoma (p = 0.73) or advanced adenomas (p = 0.20) on follow
      up examinations. LIMITATIONS: Retrospective design, differences in baseline
      colonoscopy characteristics. CONCLUSION: The results confirm the need for repeat
      examination after a colonoscopy with inadequate bowel prep, as there was
      substantial increase in adenoma detection on follow-up. There were no differences
      in outcomes between next-day versus non-next-day colonoscopy. These data support
      repeating after inadequate colonoscopy within 1 year as convenient for patient
      and physician.

PMID- 26289258
TI  - Cortactin Mediates Apoptosis of Gastric Epithelial Cells Induced by VacA Protein
      of Helicobacter pylori.
AB  - BACKGROUND: Vacuolating cytotoxin antigen (VacA) is one of the major virulence
      factors in Helicobacter pylori (H. pylori), which is responsible for cell
      vacuolar degeneration and apoptotic cell death. A candidate host factor which
      mediates this process is cortactin, a protein associated with the processes of
      colonization and adhesion of H. pylori in gastric epithelium. AIM: To investigate
      the role of cortactin in VacA-induced apoptosis of gastric epithelial cells.
      METHODS: Cortactin expression and shRNA lentiviral constructs were developed and
      transduced into the human gastric cancer cell line, AGS. VacA protein was
      purified from H. pylori cultures, acid-activated, and co-incubated with the
      transduced cell populations. Apoptosis was detected by flow cytometry, and the
      levels of the pro- and anti-apoptotic proteins Bax and Bcl-2 were determined by
      Western blot. RESULTS: Acid-activated purified VacA induced apoptosis in the
      parental AGS cells. Increased expression of cortactin (AGS/cortactin) led to a
      greater percentage of cells undergoing apoptosis. In contrast, knockdown of
      cortactin with shRNA (AGS/cortactin-shRNA) decreased the percentage of apoptotic
      cells. The protein levels of pro- and anti-apoptotic proteins Bax and Bcl-2 were
      increased and decreased in AGS/cortactin cells relative to the parental AGS
      cells. In the AGS/cortactin-shRNA cells, Bax protein levels were decreased, while
      Bcl-2 protein was increased. CONCLUSIONS: The results indicate that cortactin is
      involved in the regulation of apoptosis induced by VacA in gastric cells.

PMID- 26289259
TI  - Sense of Coherence and Defense Style Predict Sleep Difficulties in Early Non
      metastatic Colorectal Cancer.
AB  - BACKGROUND: Sleep disturbances are common in cancer patients, but little is known
      about the complex interplay between the background psychological profile, coping
      with health stressors capacities and psychological distress in the formation of
      sleep difficulties in colorectal cancer. AIMS: To study the course and to
      identify psychological predictors of sleep difficulties in early non-metastatic
      colorectal cancer patients over a one-year period. METHODS: In this 1-year
      prospective study, we assessed in 84 early non-metastatic colorectal cancer
      patients the association of psychological distress (SCL-90-R), sense of coherence
      (SOC-29), and defense styles (Defense Style Questionnaire) with sleep
      difficulties (SCL-90-R) in multiple regression models. Eighty-two patients with
      breast cancer and 50 patients with cancer of unknown primary site served as
      disease controls, and 84 matched for age and sex alleged healthy individuals
      served as healthy controls. RESULTS: Colorectal cancer patients presented more
      sleep difficulties compared to healthy participants but fewer than patients with
      breast cancer and cancer of unknown primary site. Colorectal cancer patients'
      trouble falling asleep (p = 0.033) and wakening up early in the morning (p <
      0.001) deteriorated over time. Sleep that was restless or disturbed was
      independently associated with low SOC (p = 0.046) and maladaptive defenses (p =
      0.008). Anxiety symptoms (p < 0.001) predicted deterioration in trouble falling
      asleep, while depressive symptoms (p = 0.022) and self-sacrificing defense style
      (p = 0.049) predicted deterioration in wakening up early in the morning.
      CONCLUSIONS: Psychological parameters and coping with health stressors capacities
      are independently associated with sleep difficulties in colorectal cancer
      patients, indicating the need for psychological interventions aiming at improving
      adjustment to the disease.

PMID- 26289261
TI  - Second-Look Endoscopy After ESD: Can We Finally See the Forrest from the Trees?

PMID- 26289262
TI  - GRG President's Report.

PMID- 26289260
TI  - Predictive Factors of Atelectasis Following Endoscopic Resection.
AB  - BACKGROUND AND AIM: Atelectasis is one of the pulmonary complications associated
      with anesthesia. Little is known about atelectasis following endoscopic
      procedures under deep sedation. This study evaluated the frequency, risk factors,
      and clinical course of atelectasis after endoscopic resection. METHODS: A total
      of 349 patients who underwent endoscopic resection of the upper gastrointestinal
      tract at a single academic tertiary referral center from March 2010 to October
      2013 were enrolled. Baseline characteristics and clinical data were
      retrospectively reviewed from medical records. To identify atelectasis, we
      compared the chest radiography taken before and after the endoscopic procedure.
      RESULTS: Among the 349 patients, 68 (19.5 %) had newly developed atelectasis
      following endoscopic resection. In univariate logistic regression analysis,
      atelectasis correlated significantly with high body mass index, smoking, diabetes
      mellitus, procedure duration, size of lesion, and total amount of propofol. In
      multiple logistic regression analysis, body mass index, procedure duration, and
      total propofol amount were risk factors for atelectasis following endoscopic
      procedures. Of the 68 patients with atelectasis, nine patients developed fever,
      and six patients displayed pneumonic infiltration. The others had no symptoms
      related to atelectasis. CONCLUSIONS: The incidence of radiographic atelectasis
      following endoscopic resection was nearly 20 %. Obesity, procedural time, and
      amount of propofol were the significant risk factors for atelectasis following
      endoscopic procedure. Most cases of the atelectasis resolved spontaneously with
      no sequelae.

PMID- 26289264
TI  - Optimal azimuthal orientation for Si(111) double-crystal monochromators to
      achieve the least amount of glitches in the hard X-ray region.
AB  - Simulations of the periods, split regularities and mirror symmetries of the
      glitch pattern of a Si(111) crystal along with the azimuthal angles are
      presented. The glitch patterns of Si(111) double-crystal monochromators (DCMs)
      are found to be the superposition of the two sets of glitch patterns from the two
      crystals. The optimal azimuthal orientation phi1,2 = [(2n+1)pi]/6 (n = 0, +/-1,
      +/-2...) for Si(111) DCMs to achieve the least amount of glitches in the hard X
      ray region has been suggested.

PMID- 26289263
TI  - A new method for studying sub-pulse dynamics at synchrotron sources.
AB  - The possibility of studying dynamics at time scales on the order of the pulse
      duration at synchrotron X-ray sources with present avalanche photodiode point
      detection technology is investigated, without adopting pump-probe techniques. It
      is found that sample dynamics can be characterized by counting single and double
      photon events and an analytical approach is developed to estimate the time
      required for a statistically significant measurement to be made. The amount of
      scattering required to make such a measurement possible presently within a few
      days is indicated and it is shown that at next-generation synchrotron sources
      this time will be reduced dramatically, i.e. by more than three orders of
      magnitude. The analytical results are confirmed with simulations in the frame of
      Gaussian statistics. In the future, this approach could be extended to even
      shorter time scales with the implementation of ultrafast streak cameras. 

PMID- 26289265
TI  - Influence of higher harmonics of the undulator in X-ray polarimetry and crystal
      monochromator design.
AB  - The spectrum of the undulator radiation of beamline P01 at Petra III has been
      measured after passing a multiple reflection channel-cut polarimeter. Odd and
      even harmonics up to the 15th order, as well as Compton peaks which were produced
      by the high harmonics in the spectrum, could been measured. These additional
      contributions can have a tremendous influence on the performance of the
      polarimeter and have to be taken into account for further polarimeter designs.

PMID- 26289266
TI  - Ultra-stable sub-meV monochromator for hard X-rays.
AB  - A high-resolution silicon monochromator suitable for 21.541 keV synchrotron
      radiation is presented that produces a bandwidth of 0.27 meV. The operating
      energy corresponds to a nuclear transition in (151)Eu. The first-of-its-kind,
      fully cryogenic design achieves an energy-alignment stability of 0.017 meV r.m.s.
      per day, or a 100-fold improvement over other meV-monochromators, and can
      tolerate higher X-ray power loads than room-temperature designs of comparable
      resolution. This offers the potential for significantly more accurate
      measurements of lattice excitation energies using nuclear resonant vibrational
      spectroscopy if combined with accurate energy calibration using, for example,
      high-speed Doppler shifting. The design of the monochromator along with its
      performance and impact on transmitted beam properties are presented.

PMID- 26289267
TI  - Optimized IR synchrotron beamline design.
AB  - Synchrotron infrared beamlines are powerful tools on which to perform
      spectroscopy on microscopic length scales but require working with large bending
      magnet source apertures in order to provide intense photon beams to the
      experiments. Many infrared beamlines use a single toroidal-shaped mirror to focus
      the source emission which generates, for large apertures, beams with significant
      geometrical aberrations resulting from the shape of the source and the beamline
      optics. In this paper, an optical layout optimized for synchrotron infrared
      beamlines, that removes almost totally the geometrical aberrations of the source,
      is presented and analyzed. This layout is already operational on the IR beamline
      of the Brazilian synchrotron. An infrared beamline design based on a SOLEIL
      bending-magnet source is given as an example, which could be useful for future IR
      beamline improvements at this facility. 

PMID- 26289268
TI  - Optimizing X-ray mirror thermal performance using matched profile cooling.
AB  - To cover a large photon energy range, the length of an X-ray mirror is often
      longer than the beam footprint length for much of the applicable energy range. To
      limit thermal deformation of such a water-cooled X-ray mirror, a technique using
      side cooling with a cooled length shorter than the beam footprint length is
      proposed. This cooling length can be optimized by using finite-element analysis.
      For the Kirkpatrick-Baez (KB) mirrors at LCLS-II, the thermal deformation can be
      reduced by a factor of up to 30, compared with full-length cooling. Furthermore,
      a second, alternative technique, based on a similar principle is presented: using
      a long, single-length cooling block on each side of the mirror and adding
      electric heaters between the cooling blocks and the mirror substrate. The
      electric heaters consist of a number of cells, located along the mirror length.
      The total effective length of the electric heater can then be adjusted by
      choosing which cells to energize, using electric power supplies. The residual
      height error can be minimized to 0.02 nm RMS by using optimal heater parameters
      (length and power density). Compared with a case without heaters, this residual
      height error is reduced by a factor of up to 45. The residual height error in the
      LCLS-II KB mirrors, due to free-electron laser beam heat load, can be reduced by
      a factor of ~11 below the requirement. The proposed techniques are also effective
      in reducing thermal slope errors and are, therefore, applicable to white beam
      mirrors in synchrotron radiation beamlines.

PMID- 26289269
TI  - Py4Syn: Python for synchrotrons.
AB  - In this report, Py4Syn, an open-source Python-based library for data acquisition,
      device manipulation, scan routines and other helper functions, is presented.
      Driven by easy-to-use and scalability ideals, Py4Syn offers control system
      agnostic solution and high customization level for scans and data output,
      covering distinct techniques and facilities. Here, most of the library
      functionalities are described, examples of use are shown and ideas for future
      implementations are presented.

PMID- 26289270
TI  - High-rate dead-time corrections in a general purpose digital pulse processing
      system.
AB  - Dead-time losses are well recognized and studied drawbacks in counting and
      spectroscopic systems. In this work the abilities on dead-time correction of a
      real-time digital pulse processing (DPP) system for high-rate high-resolution
      radiation measurements are presented. The DPP system, through a fast and slow
      analysis of the output waveform from radiation detectors, is able to perform
      multi-parameter analysis (arrival time, pulse width, pulse height, pulse shape,
      etc.) at high input counting rates (ICRs), allowing accurate counting loss
      corrections even for variable or transient radiations. The fast analysis is used
      to obtain both the ICR and energy spectra with high throughput, while the slow
      analysis is used to obtain high-resolution energy spectra. A complete
      characterization of the counting capabilities, through both theoretical and
      experimental approaches, was performed. The dead-time modeling, the throughput
      curves, the experimental time-interval distributions (TIDs) and the counting
      uncertainty of the recorded events of both the fast and the slow channels,
      measured with a planar CdTe (cadmium telluride) detector, will be presented. The
      throughput formula of a series of two types of dead-times is also derived. The
      results of dead-time corrections, performed through different methods, will be
      reported and discussed, pointing out the error on ICR estimation and the
      simplicity of the procedure. Accurate ICR estimations (nonlinearity < 0.5%) were
      performed by using the time widths and the TIDs (using 10 ns time bin width) of
      the detected pulses up to 2.2 Mcps. The digital system allows, after a simple
      parameter setting, different and sophisticated procedures for dead-time
      correction, traditionally implemented in complex/dedicated systems and time
      consuming set-ups.

PMID- 26289271
TI  - Towards a microchannel-based X-ray detector with two-dimensional spatial and time
      resolution and high dynamic range.
AB  - X-ray detectors that combine two-dimensional spatial resolution with a high time
      resolution are needed in numerous applications of synchrotron radiation. Most
      detectors with this combination of capabilities are based on semiconductor
      technology and are therefore limited in size. Furthermore, the time resolution is
      often realised through rapid time-gating of the acquisition, followed by a slower
      readout. Here, a detector technology is realised based on relatively inexpensive
      microchannel plates that uses GHz waveform sampling for a millimeter-scale
      spatial resolution and better than 100 ps time resolution. The technology is
      capable of continuous streaming of time- and location-tagged events at rates
      greater than 10(7) events per cm(2). Time-gating can be used for improved dynamic
      range.

PMID- 26289272
TI  - Single-crystal X-ray diffraction and resonant X-ray magnetic scattering at helium
      3 temperatures in high magnetic fields at beamline P09 at PETRA III.
AB  - The resonant scattering and diffraction beamline P09 at PETRA III at DESY is
      equipped with a 14 T vertical field split-pair magnet. A helium-3 refrigerator is
      available that can be fitted inside the magnet's variable-temperature insert.
      Here the results of a series of experiments aimed at determining the beam
      conditions permitting operations with the He-3 insert are presented. By measuring
      the tetragonal-to-orthorhombic phase transition occurring at 2.1 K in the Jahn
      Teller compound TmVO4, it is found that the photon flux at P09 must be attenuated
      down to 1.5 * 10(9) photons s(-1) for the sample to remain at temperatures below
      800 mK. Despite such a reduction of the incident flux and the subsequent use of a
      Cu(111) analyzer, the resonant X-ray magnetic scattering signal at the Tm LIII
      absorption edge associated with the spin-density wave in TmNi2B2C below 1.5 K is
      intense enough to permit a complete study in magnetic field and at sub-Kelvin
      temperatures to be carried out.

PMID- 26289273
TI  - XAS analysis of iron and palladium bonded to a polysaccharide produced
      anaerobically by a strain of Klebsiella oxytoca.
AB  - Klebsiella oxytoca BAS-10 ferments citrate to acetic acid and CO2, and secretes a
      specific exopolysaccharide (EPS), which is able to bind different metallic
      species. These biomaterials may be used for different biotechnological purposes,
      including applications as innovative green biogenerated catalysts. In production
      of biogenerated Pd species, the Fe(III) as ferric citrate is added to anaerobic
      culture of K. oxytoca BAS-10, in the presence of palladium species, to increase
      the EPS secretion and improve Pd-EPS yield. In this process, bi-metallic (FePd
      EPS) biomaterials were produced for the first time. The morphology of bi-metallic
      EPS, and the chemical state of the two metals in the FePd-EPS, are investigated
      by transmission electron microscopy, Fourier transform infra-red spectroscopy,
      micro-X-ray fluorescence, and X-ray absorption spectroscopy methods (XANES and
      EXAFS), and compared with mono-metallic Pd-EPS and Fe-EPS complexes. Iron in FePd
      EPS is in the mineralized form of iron oxides/hydroxides, predominantly in the
      form of Fe(3+), with a small amount of Fe(2+) in the structure, most probably a
      mixture of different nano-crystalline iron oxides and hydroxides, as in mono
      metallic Fe-EPS. Palladium is found as Pd(0) in the form of metallic
      nanoparticles with face-centred cubic structure in both bi-metallic (FePd-EPS)
      and mono-metallic (Pd-EPS) species. In bi-metallic species, Pd and Fe
      nanoparticles agglomerate in larger clusters, but they remain spatially
      separated. The catalytic ability of bi-metallic species (FePd-EPS) in a
      hydrodechlorination reaction is improved in comparison with mono-metallic Pd-EPS.

PMID- 26289274
TI  - Development of dispersive XAFS system for analysis of time-resolved spatial
      distribution of electrode reaction.
AB  - Apparatus for a technique based on the dispersive optics of X-ray absorption fine
      structure (XAFS) has been developed at beamline BL-5 of the Synchrotron Radiation
      Center of Ritsumeikan University. The vertical axis of the cross section of the
      synchrotron light is used to disperse the X-ray energy using a cylindrical
      polychromator and the horizontal axis is used for the spatially resolved analysis
      with a pixel array detector. The vertically dispersive XAFS (VDXAFS) instrument
      was designed to analyze the dynamic changeover of the inhomogeneous electrode
      reaction of secondary batteries. The line-shaped X-ray beam is transmitted
      through the electrode sample, and then the dispersed transmitted X-rays are
      detected by a two-dimensional detector. An array of XAFS spectra in the linear
      footprint of the transmitted X-ray on the sample is obtained with the time
      resolution of the repetition frequency of the detector. Sequential measurements
      of the space-resolved XAFS data are possible with the VDXAFS instrument. The time
      and spatial resolutions of the VDXAFS instrument depend on the flux density of
      the available X-ray beam and the size of the light source, and they were
      estimated as 1 s and 100 um, respectively. The electrode reaction of the LiFePO4
      lithium ion battery was analyzed during the constant current charging process and
      during the charging process after potential jumping.

PMID- 26289275
TI  - Investigating structural aspects to understand the putative/claimed non-toxicity
      of the Hg-based Ayurvedic drug Rasasindura using XAFS.
AB  - XANES- and EXAFS-based analysis of the Ayurvedic Hg-based nano-drug Rasasindura
      has been performed to seek evidence of its non-toxicity. Rasasindura is
      determined to be composed of single-phase alpha-HgS nanoparticles (size ~24 nm),
      free of Hg(0) or organic molecules; its structure is determined to be robust (<3%
      defects). The non-existence of Hg(0) implies the absence of Hg-based toxicity and
      establishes that chemical form, rather than content of heavy metals, is the
      correct parameter for evaluating the toxicity in these drugs. The stable alpha
      HgS form (strong Hg-S covalent bond and robust particle character) ensures the
      integrity of the drug during delivery and prevention of its reduction to Hg(0)
      within the human body. Further, these comparative studies establish that
      structural parameters (size dispersion, coordination configuration) are better
      controlled in Rasasindura. This places the Ayurvedic synthesis method on par with
      contemporary techniques of nanoparticle synthesis.

PMID- 26289276
TI  - On EXAFS Debye-Waller factor and recent advances.
AB  - The effects of structural and vibrational disorder on the EXAFS signals are
      parameterized in terms of the Debye Waller (DW) factor. Here the vibrational
      contribution is addressed, which for most systems can be singled out by studying
      the temperature dependence of the EXAFS DW factor, which corresponds to a good
      accuracy to the parallel mean square relative displacement (MSRD) around the
      inter-atomic equilibrium distance. By comparing the first-shell EXAFS thermal
      expansion with the crystallographic thermal expansion one can evaluate the
      perpendicular MSRD. The results of recent measurements on copper and on several
      tetrahedral semiconductors are here critically compared and some properties of
      the MSRDs are discussed, such as the dependence of correlation, force constants
      and vibrational anisotropy on crystal structure and bond ionicity as well as the
      relative merits of the correlated Debye and Einstein models. The anharmonic
      contribution to the parallel MSRD of CdTe has been evaluated and a quasi-harmonic
      analysis has been attempted, leading to an estimation of the bond Gruneisen
      parameter.

PMID- 26289277
TI  - Muffin-tin potentials in EXAFS analysis.
AB  - Muffin-tin potentials are the standard tool for calculating the potential surface
      of a cluster of atoms for use in the analysis of extended X-ray absorption fine
      structure (EXAFS) data. The set of Cartesian coordinates used to define the
      positions of atoms in the cluster and to calculate the muffin-tin potentials is
      commonly also used to enumerate the scattering paths used in the EXAFS data
      analysis. In this paper, it is shown that these muffin-tin potentials are
      sufficiently robust to be used to examine quantitatively contributions to the
      EXAFS data from scattering geometries not represented in the original cluster.

PMID- 26289278
TI  - A novel imaging tool for hepatic portal system using phase contrast technique
      with hydrogen peroxide-generated O2 gas.
AB  - The objective of this study was to investigate the potential of hydrogen peroxide
      generated oxygen gas-based phase contrast imaging (PCI) for visualizing mouse
      hepatic portal veins. The O2 gas was made from the reaction between H2O2 and
      catalase. The gas production was imaged by PCI in real time. The H2O2 was
      injected into the enteric cavity of the lower sigmoid colon to produce O2 in the
      submucosal venous plexus. The generated O2 gas could be finally drained into
      hepatic portal veins. Absorption contrast imaging (ACI) and PCI of O2-filled
      portal veins were performed and compared. PCI offers high resolution and real
      time visualization of the O2 gas production. Compared with O2-based ACI, O2-based
      PCI significantly enhanced the revealing of the portal vein in vivo. It is
      concluded that O2-based PCI is a novel and promising imaging modality for future
      studies of portal venous disorders in mice models. 

PMID- 26289279
TI  - Ring artifacts correction in compressed sensing tomographic reconstruction.
AB  - Ring artifacts are a very common problem in tomographic reconstruction, and
      numerous methods exist to either pre-process the sinogram or correct the
      reconstructed slice. A novel approach to perform the correction as part of the
      reconstruction process is presented. It is shown that for iterative techniques,
      which amount to optimizing an objective function, the ring artifacts correction
      can be easily integrated in the formalism, enabling simultaneous slice
      reconstruction and ring artifacts correction. This method is tested and compared
      with mainstream correction techniques for both simulated and experimental data.
      Results show that the correction is efficient, especially for undersampled
      datasets. This technique is included in the PyHST2 code which is used at the
      European Synchrotron Radiation Facility for tomographic reconstruction.

PMID- 26289280
TI  - Exploring experimental parameter choice for rapid speckle-tracking phase-contrast
      X-ray imaging with a paper analyzer.
AB  - Phase-contrast X-ray imaging using a paper analyzer enables the visualization of
      X-ray transparent biological structures using the refractive properties of the
      sample. The technique measures the sample-induced distortions of a spatially
      random reference pattern to retrieve quantitative sample information. This phase
      contrast method is promising for biomedical application due to both a simple
      experimental set-up and a capability for real-time imaging. The authors explore
      the experimental configuration required to achieve robustness and accuracy in
      terms of (i) the paper analyzer feature size, (ii) the sample-to-detector
      distance, and (iii) the exposure time. Results using a synchrotron source confirm
      that the technique achieves accurate phase retrieval with a range of paper
      analyzers and at exposures as short as 0.5 ms. These exposure times are
      sufficiently short relative to characteristic physiological timescales to enable
      real-time dynamic imaging of living samples. A theoretical guide to the choice of
      sample-to-detector distance is also derived. While the measurements are specific
      to the set-up, these guidelines, the example speckle images, the strategies for
      analysis in the presence of noise and the experimental considerations and
      discussion will be of value to those who wish to use the speckle-tracking paper
      analyzer technique.

PMID- 26289281
TI  - A plug-and-measure diagnostic tool for flux, resolution and beam size of a soft X
      ray beamline.
AB  - A compact multi-functional diagnostic tool has been installed for commissioning
      beamlines at the Taiwan Light Source. For a photon beam, the instrument can
      measure the photon flux, energy resolution and beam size, consecutively with a
      photodiode or gold mesh, a windowless gas cell and a movable fluorescence screen
      viewport. Two gratings with ruling densities of 350 and 1000 lines mm(-1) and
      dispersing photons of energies from 80 to 1200 eV were calibrated with a photon
      flux of 10(11) photon s(-1) at slit openings of 50 um * 50 um; a maximum
      resolving power of greater than 10000 was certified with an absorption spectra of
      gaseous samples. Pressure differences over four orders of magnitude were achieved
      between the ion chamber and the flux measurement chamber with a single capillary
      differential pumping stage. A sequence of beam profiles was measured by moving
      continuously in the vicinity of the nominal focal positions. This tool is useful
      in commissioning or trouble-shooting at most beamlines in a synchrotron facility.

PMID- 26289282
TI  - Time delay measurement in the frequency domain.
AB  - Pump-probe studies at synchrotrons using X-ray and laser pulses require accurate
      determination of the time delay between pulses. This becomes especially important
      when observing ultrafast responses with lifetimes approaching or even less than
      the X-ray pulse duration (~100 ps). The standard approach of inspecting the time
      response of a detector sensitive to both types of pulses can have limitations due
      to dissimilar pulse profiles and other experimental factors. Here, a simple
      alternative is presented, where the frequency response of the detector is
      monitored versus time delay. Measurements readily demonstrate a time resolution
      of ~1 ps. Improved precision is possible by simply extending the data acquisition
      time.

PMID- 26289283
TI  - Design of a mouse restraint for synchrotron-based computed tomography imaging.
AB  - High-resolution computed tomography (CT) imaging of a live animal within a lead
      lined synchrotron light hutch presents several unique challenges. In order to
      confirm that the animal is under a stable plane of anaesthesia, several
      physiological parameters (e.g. heart rate, arterial oxygen saturation, core body
      temperature and respiratory rate) must be remotely monitored from outside the
      imaging hutch. In addition, to properly scan the thoracic region using CT, the
      animal needs to be held in a vertical position perpendicular to the fixed angle
      of the X-ray beam and free to rotate 180 degrees -360 degrees . A new X-ray
      transparent mouse restraint designed and fabricated using computer-aided design
      software and three-dimensional rapid prototype printing has been successfully
      tested at the Biomedical Imaging and Therapy bending-magnet (BMIT-BM) beamline at
      the Canadian Light Source.

PMID- 26289284
TI  - A soft X-ray plane-grating monochromator optimized for elliptical dipole
      radiation from modern sources.
AB  - A new but yet well proven way of making elliptically polarized dipole radiation
      from the BESSY II storage ring applicable to the SX700-type collimated plane
      grating monochromator PM3 is described. It is shown that due to the limited
      vertical acceptance of the grating a simple use of vertical apertures is not
      possible in this case. Rather, deflecting the beam upwards or downwards by
      rotating the vertically collimating toroidal mirror M1 around the light axis
      leads to excellent performance. The resulting detuning of the photon energy can
      be taken into account by a readjustment of the monochromator internal plane
      mirror M2. The energy resolution of the beamline is not affected by the non-zero
      'roll' of the collimating mirror.

PMID- 26289285
TI  - A sub-micrometer resolution hard X-ray microprobe system of BL8C at Pohang Light
      Source.
AB  - A microprobe system has been installed on the nanoprobe/XAFS beamline (BL8C) at
      PLS-II, South Korea. Owing to the reproducible switch of the gap of the in-vacuum
      undulator (IVU), the intense and brilliant hard X-ray beam of an IVU can be used
      in X-ray fluorescence (XRF) and X-ray absorption fine-structure (XAFS)
      experiments. For high-spatial-resolution microprobe experiments a Kirkpatrick
      Baez mirror system has been used to focus the millimeter-sized X-ray beam to a
      micrometer-sized beam. The performance of this system was examined by a
      combination of micro-XRF imaging and micro-XAFS of a beetle wing. These results
      indicate that the microprobe system of the BL8C can be used to obtain the
      distributions of trace elements and chemical and structural information of
      complex materials. 

PMID- 26289286
TI  - Upgrade of beamline BL08B at Taiwan Light Source from a photon-BPM to a double
      grating SGM beamline.
AB  - During the last 20 years, beamline BL08B has been upgraded step by step from a
      photon beam-position monitor (BPM) to a testing beamline and a single-grating
      beamline that enables experiments to record X-ray photo-emission spectra (XPS)
      and X-ray absorption spectra (XAS) for research in solar physics, organic
      semiconductor materials and spinel oxides, with soft X-ray photon energies in the
      range 300-1000 eV. Demands for photon energy to extend to the extreme ultraviolet
      region for applications in nano-fabrication and topological thin films are
      increasing. The basic spherical-grating monochromator beamline was again upgraded
      by adding a second grating that delivers photons of energy from 80 to 420 eV.
      Four end-stations were designed for experiments with XPS, XAS, interstellar
      photoprocess systems (IPS) and extreme-ultraviolet lithography (EUVL) in the
      scheduled beam time. The data from these experiments show a large count rate in
      core levels probed and excellent statistics on background normalization in the L
      edge adsorption spectrum.

PMID- 26289287
TI  - SIMPLEX: simulator and postprocessor for free-electron laser experiments.
AB  - SIMPLEX is a computer program developed for simulating the amplification process
      of free-electron lasers (FELs). It numerically solves the so-called FEL equations
      describing the evolution of the radiation field and growth of microbunching while
      the electron beam travels along the undulator. In order to reduce the numerical
      cost, the FEL equations have been reduced to more convenient forms for numerical
      implementation by applying reasonable approximations. SIMPLEX is equipped with a
      postprocessor to facilitate the retrieval of desired information from the
      simulation results, which is crucial for practical applications such as designing
      the beamline and analyzing the experimental results.

PMID- 26289288
TI  - Just for us?
AB  - It is a regrettable decision by Karlsruhe Institute of Technology that ANKA, the
      Angstromquelle Karlsruhe, is terminating its external synchrotron user support
      program. ANKA has an excellent performance review grading sheet and has been a
      valuable source and resource to international users for over a decade. There is
      concern among users that ANKA's decision could become an example for other
      synchrotrons as well.

PMID- 26289289
TI  - On the ANKA decision: a response to Braun's Just for us?
AB  - KIT's Executive Board has decided to discontinue the operation of the synchrotron
      radiation facility ANKA within category LK-II (user facility) of the Helmholtz
      Association and continue operation in LK-I (research). The KIT Senate confirmed
      this decision. Some aspects of the background and the rationale leading to this
      change are explained. 

PMID- 26289290
TI  - Novel factor H mutation associated with familial membranoproliferative
      glomerulonephritis type I.
AB  - BACKGROUND: Idiopathic membranoproliferative glomerulonephritis (MPGN) is a rare
      disease, accounting for 3-5% of all cases of primary nephritic syndrome. We
      report an uncommon case of familial MPGN type I associated with a new mutation in
      the complement factor H gene (CFH). METHODS: Clinical data were collected on
      three siblings with known factor H deficiency who presented with MPGN. All
      underwent immunological and genetic assays. Their parents and ten healthy adults
      served as controls for the DNA analysis. RESULTS: All three children presented
      with recurrent episodes of hematuria and proteinuria, the youngest starting at
      age 5 months. One child currently has nephrotic syndrome and end-stage renal
      disease. All of the children were found to be homozygous for a C.262C > A
      (p.Pro88Thr) mutation in exon 3 of CFH that is associated with a
      quantitative/functional deficiency of factor H. The parents of the three siblings
      were found to be heterozygous for the mutation. None of the controls carried this
      mutation. CONCLUSIONS: Different mutations in CFH may be responsible for
      different glomerular diseases, including MPGN type I. A modifier gene or an
      environmental trigger may contribute to this phenotype-genotype discrepancy.
      Understanding the role of the alternative complement pathway in this disease
      would allow us to offer these patients more targeted therapy, including a
      clinical trial of eculizumab.

PMID- 26289291
TI  - A young girl with an unusual cause of acute kidney injury: Questions.

PMID- 26289292
TI  - A young girl with an unusual cause of acute kidney injury: Answers.

PMID- 26289293
TI  - Antimicrobial Susceptibilities of Aerobic Isolates from Respiratory Samples of
      Young New Zealand Horses.
AB  - BACKGROUND: Decreased efficacy of antimicrobials and increased prevalence of
      multidrug resistance (MDR) is of concern worldwide. OBJECTIVES: To describe and
      analyze bacterial culture and antimicrobial susceptibilities from respiratory
      samples submitted from young horses (4 weeks to 3 years old). ANIMALS: Samples
      from 289 horses were submitted to a commercial laboratory. METHODS: A
      retrospective database search of submissions made to a New Zealand veterinary
      laboratory between April 2004 and July 2014. The results of in vitro
      susceptibility testing by Kirby-Bauer disc diffusion were described and tabulated
      for the major bacterial species isolated. Multiple correspondence analysis (MCA)
      was used to describe the clustering of MDR isolates and selected demographic
      variables. RESULTS: Overall, 774 bacterial isolates were cultured from 237
      horses, the majority of these isolates were gram-positive (67.6%; 95% CI 64.3
      70.9%). Streptococcus spp. were the most common genus of bacteria isolated and
      were 40.1% (95% CI 36.6-43.5%) of the isolates cultured. Susceptibility of
      Streptococcus spp. to penicillin, gentamicin, and ceftiofur was >85%. Overall,
      gram-negative susceptibility to ceftiofur, tetracycline, and TMPS was <75%. MDR
      was defined as resistance to 3 or more antimicrobials, and was found in 39.2% of
      horses (93/237; 95% CI 33.0-45.5%). CONCLUSIONS AND CLINICAL IMPORTANCE: Culture
      and susceptibility results have highlighted that MDR is an emerging problem for
      young horses in New Zealand (NZ), where a bacterial respiratory infection is
      suspected. This should be considered when prescribing antimicrobials, and
      emphasizes the need for submission of samples for culture and susceptibility.

PMID- 26289295
TI  - Erratum.

PMID- 26289294
TI  - Retrospective analysis of factors associated with outcome of proximal
      interphalangeal joint arthrodesis in 82 horses including Warmblood and
      Thoroughbred sport horses and Quarter Horses (1992-2014).
AB  - REASONS FOR PERFORMING STUDY: Outcomes associated with arthrodesis of the
      proximal interphalangeal (PIP) joint in Quarter Horses used for Western
      performance activities are well documented but little is known regarding outcomes
      for other types of horses. OBJECTIVES: To identify factors associated with
      outcomes, including breed and activity, after arthrodesis of the PIP joint in
      Warmbloods, Thoroughbreds and Quarter Horses. STUDY DESIGN: Retrospective case
      series. METHODS: Surgical case records of 82 Quarter Horses principally engaged
      in Western performance and Thoroughbred or Warmblood breeds principally engaged
      in showing, showjumping and dressage, with arthrodesis of the PIP joint were
      reviewed. Arthrodesis was performed with either 3 transarticular cortex bone
      screws placed in lag fashion, a dynamic compression plate (DCP) with 2
      transarticular cortex bone screws placed in lag fashion, or a locking compression
      plate (LCP) with 2 transarticular cortex bone screws placed in lag fashion.
      Demographic data, clinical presentation, radiographic findings, surgical
      technique, post operative treatment and complications were recorded. Long-term
      follow-up was obtained for all 82 horses. RESULTS: Osteoarthritis of the PIP
      joint was the most common presenting condition requiring arthrodesis, which was
      performed with either the 3 screw technique (n = 41), DCP fixation (n = 22), or
      LCP fixation (n = 19). Post operatively, 23/31 (74%) Warmbloods/Thoroughbreds and
      44/51 (87%) Quarter Horses achieved successful outcomes. Thirteen of 23 (57%)
      Warmbloods/Thoroughbreds and 24 of 38 (63%) Quarter Horses, used for athletic
      performance, returned to successful competition. Within this subgroup of horses
      engaged in high-level activity, regardless of breed type, horses undergoing
      hindlimb arthrodesis were significantly more likely to return to successful
      competition (73%; 33/45) than those with forelimb arthrodesis (25%; 4/16, P =
      0.002). CONCLUSIONS: Arthrodesis of the PIP joint in Warmbloods/Thoroughbreds and
      Quarter Horses results in a favourable outcome for return to their intended use
      and athletic competition.

PMID- 26289296
TI  - Easing the wheeze.

PMID- 26289297
TI  - Epithelial DLD-1 Cells with Disrupted E-cadherin Gene Retain the Ability to Form
      Cell Junctions and Apico-basal Polarity.
AB  - Gene editing methods were applied to the study of E-cadherin function in
      epithelial cells. The E-cadherin gene in epithelial DLD-1 cells was ablated using
      TALEN. The resultant cells showed round fibroblast-like morphology and had almost
      no Ca(2+)-dependent cell aggregation activity. E-cadherin re-expression in the
      knockout cells restored epithelial cell morphology and strong Ca(2+)-dependent
      cell-cell adhesion activity, indicating that the knockout cells retained the
      ability to support cadherin function. The knockout cells showed partial
      localization of desmoplakin and ZO-1 at intercellular contact sites. The
      transfectants expressing mutant E-cadherin lacking the cytoplasmic domain showed
      clear localization of desmoplakin and ZO-1 at cell-cell contact sites, although
      the cells had only weak Ca(2+)-dependent cell adhesion activity. Electron
      microscopy revealed the formation of intercellular junctions and apico-basal
      polarity in these cells. A portion of these cells occasionally formed an
      epithelial-like structure after prolonged culture. When the cells were treated
      with blebbistatin, the localization was enhanced. However, the localization was
      incomplete and contained defects. Double-knockout MDCK cells for the E-cadherin
      and cadherin-6 genes showed similar results, suggesting that the above properties
      were general. The present results showed that an epithelial-like structure could
      be formed without E-cadherin, but that the construction of mature epithelia
      requires E-cadherin. 

PMID- 26289298
TI  - Palmoplantar psoriasis, a frequent and severe clinical type of psoriasis in
      children.

PMID- 26289299
TI  - Large Fragment of DNA Polymerase I from Geobacillus sp. 777: Cloning and
      Comparison with DNA Polymerases I in Practical Applications.
AB  - A truncated gene of DNA polymerase I from the thermophilic bacteria Geobacillus
      sp. 777 encoding a large fragment of enzyme (LF Gss pol) was cloned and
      sequenced. The resulting sequence is 1776-bp long and encodes a 592 aa protein
      with a predicted molecular mass of 69.8 kDa. Enzyme was overexpressed in E. coli,
      purified by metal-chelate chromatography, and biochemically characterized. The
      specific activity of LF Gss pol is 104,000 U/mg (one unit of enzyme was defined
      as the amount of enzyme that incorporated 10 nmol of dNTP into acid insoluble
      material in 30 min at 65  degrees C). The properties of LF Gss pol were compared
      to commercially available large fragments of DNA polymerase I from G.
      stearothermophilus (LF Bst pol) and Bacillus smithii (LF Bsm pol). Studied
      enzymes showed maximum activity at similar pH and concentrations of
      monovalent/divalent ions, whereas LF Gss pol and LF Bst pol were more
      thermostable than LF Bsm pol. LF Gss pol is more resistant to enzyme inhibitors
      (SYBR Green I, heparin, ethanol, urea, blood plasma) in comparison with LF Bst
      pol and LF Bsm pol. LF Gss pol is also suitable for loop-mediated isothermal
      amplification and whole genome amplification of human genomic DNA. 

PMID- 26289300
TI  - Investigation and Expression of the Secoisolariciresinol Dehydrogenase Gene
      Involved in Podophyllotoxin Biosynthesis.
AB  - Podophyllotoxin (PPT) is a plant natural product that serves as a precursor for
      the synthesis of many well-known chemotherapeutic drugs. The limited availability
      and high demand for the source plants of PPT have led to the exploration of
      alternative sources for this compound. In this study, we utilized the endophytic
      fungus Phialocephala podophylli (strain PPE7) that we isolated from the rhizomes
      of Podophyllum peltatum and is known to produce detectable amounts of PPT in
      broth culture. To date, the complete PPT biosynthetic pathway has yet to be
      determined in any species. Since fungi are well known for clustering genes that
      belong to secondary metabolite pathways, use of a fungal system for investigation
      of the PPT biosynthesis genes may ultimately lead to elucidation of the entire
      pathway. In this study, we investigated the secoisolariciresinol dehydrogenase
      (SD) gene that facilitates the dehydrogenation of secoisolariciresinol to form
      matairesinol, a mid-pathway intermediate product in PPT biosynthesis. We utilized
      PCR amplification to acquire the complete SD gene sequence in PPE7 and opted to
      synthesize the P. peltatum SD sequence for expression. Through western blotting,
      we confirmed the expression of the recombinant SD (PpSD) and verified protein
      functionality with a bioconversion assay followed by HPLC and LC-MS analyses.
      Here, we report the identification of the SD gene in PPE7; this is the first
      report of the SD gene in an endophytic fungus. Additionally, we established the
      groundwork for the future expression of the complete PPT biosynthetic pathway in
      the heterologous host Pichia pastoris. 

PMID- 26289301
TI  - Adults with sickle cell disease may perform cognitive tests as well as controls
      when processing speed is taken into account: a preliminary case-control study.
AB  - AIMS: This study aimed to: (1) evaluate cognitive function among adults with
      sickle cell disease using a computer-administered neuropsychological test; and
      (2) replicate previously identified differences in processing speed between
      patients with sickle cell disease and controls. BACKGROUND: Previous evidence
      suggests that, compared with controls, adult patients with sickle cell disease
      have poorer cognitive functioning across most domains but the most significant
      deficits appear to be in the area of processing speed. DESIGN: Cross-sectional
      case-control study conducted from June 2008-June 2010. METHODS: Cognitive
      functioning was measured using computerized, self-administered,
      neuropsychological tests among 31 patients with sickle cell disease and 17
      controls matched for age, gender and race. The assessment averaged 30 minutes and
      scores were recorded for seven computerized tests: verbal and visual memory,
      finger tapping, symbol digit coding, Stroop test, shifting attention and
      continuous performance. RESULTS: Patients with sickle cell disease scored 10.76
      points lower on the CNS Vital Signs processing speed domain than controls.
      Although non-significant, patients scored 5.73 points lower on the full index
      than controls but after adjusting for processing speed, mean scores for patients
      were 3 points greater compared with controls. Differences in executive
      functioning and attention were not significant and memory did not differ between
      groups. CONCLUSION: Using a brief, computer-administered 30-minute
      neuropsychological test, we were able to replicate previous findings showing a
      greater than 10-point deficit in processing speed among patients with sickle cell
      disease. When differences in processing speed are taken into account, patients
      perform equally well or better than controls on cognitive tasks.

PMID- 26289302
TI  - Theoretical investigation on the performance of DNA electrophoresis under
      programmed step electric field strength: Two-step condition.
AB  - Programmed step electric field strength is a simple-to-use technique that has
      already been reported to be effective to enhance the efficiency or speed of DNA
      electrophoresis. However, a global understanding and the details of this
      technique are still vague. In this paper, we investigated the influence of
      programmed step electric field strength by theoretical calculation and
      concentrated on a basic format named as two-step electric field strength. Both
      subtypes of two-step electric field strength conditions were considered. The
      important parameters, such as peak spacing, peak width, resolution, and migration
      time, were calculated in theory to understand the performance of DNA
      electrophoresis under programmed step electric field strength. The influence of
      two-step electric field strength on DNA electrophoresis was clearly revealed on a
      diagram of resolution versus migration time. Both resolution and speed of DNA
      electrophoresis under two-step electric field strength conditions are simply
      expressed by the shape of curves in the diagram. The possible shapes of curve
      were explored by calculation and shown in this paper. The subtype II of two-step
      electric field strength brings drastic variation on the resolution. Its
      limitations of enhancement and deterioration of resolution were predicted in
      theory. 

PMID- 26289303
TI  - Adolescence and polycystic ovary syndrome: current concepts on diagnosis and
      treatment.
AB  - BACKGROUND: Adolescence is a time characterised by changes in reproductive
      hormones and menstrual patterns, which makes it difficult to diagnose polycystic
      ovary syndrome (PCOS) in this population. The diagnosis of PCOS has a great
      physical and psychosocial impact on the young person. Despite the importance of a
      diagnosis of PCOS at adolescence, data available are limited. AIMS: This review
      focuses on analysing markers of PCOS diagnosis and possible treatments in
      adolescence. RESULTS: Although, during adolescence, diagnosis criteria of PCOS
      overlap with physiological changes including clinical manifestations of
      hyperandrogenism (acne and hirsutism), oligo/amenorrhoea, anovulation and ovarian
      microcysts, there is agreement that irregular menses and hyperandrogenaemia
      should be used to diagnose PCOS in this population. Moreover, considering that
      PCOS phenotype could change through the reproductive age and that adolescents
      display heterogeneous ovarian morphology, it has been proposed that diagnosis of
      PCOS should be confirmed after the age of 18. The first-line treatment for
      menstrual irregularity and hirsutism are oral contraceptive pills (OCPs) and for
      obesity and metabolic abnormalities are lifestyle changes. Insulin-sensitizer
      drugs, such as metformin, may be added to the treatment in the presence of
      metabolic alterations. Antiandrogen drugs may also be associated for treating
      moderate to severe hirsutism. During adolescence, physiological changes overlap
      with signs and symptoms of PCOS; thus the diagnosis criteria should be carefully
      considered. Regarding the treatment of adolescents with PCOS, non-pharmacological
      interventions include lifestyle changes. Pharmacological treatments comprise
      OCPs, antiandrogens and metformin, used isolated or combined. CONCLUSIONS: During
      adolescence, physiological changes overlap with signs and symptoms of PCOS; thus
      the diagnosis criteria should be carefully considered. Regarding the treatment of
      adolescents with PCOS, non-pharmacological interventions include lifestyle
      changes. Pharmacological treatments comprise OCPs, antiandrogens and metformin,
      used isolated or combined.

PMID- 26289304
TI  - Patient- and therapy-related factors associated with the incidence of xerostomia
      in nasopharyngeal carcinoma patients receiving parotid-sparing helical
      tomotherapy.
AB  - We investigated the incidence of moderate to severe patient-reported xerostomia
      among nasopharyngeal carcinoma (NPC) patients treated with helical tomotherapy
      (HT) and identified patient- and therapy-related factors associated with acute
      and chronic xerostomia toxicity. The least absolute shrinkage and selection
      operator (LASSO) normal tissue complication probability (NTCP) models were
      developed using quality-of-life questionnaire datasets from 67 patients with NPC.
      For acute toxicity, the dosimetric factors of the mean doses to the ipsilateral
      submandibular gland (Dis) and the contralateral submandibular gland (Dcs) were
      selected as the first two significant predictors. For chronic toxicity, four
      predictive factors were selected: age, mean dose to the oral cavity (Doc),
      education, and T stage. The substantial sparing data can be used to avoid
      xerostomia toxicity. We suggest that the tolerance values corresponded to a 20%
      incidence of complications (TD20) for Dis = 39.0 Gy, Dcs = 38.4 Gy, and Doc =
      32.5 Gy, respectively, when mean doses to the parotid glands met the QUANTEC 25
      Gy sparing guidelines. To avoid patient-reported xerostomia toxicity, the mean
      doses to the parotid gland, submandibular gland, and oral cavity have to meet the
      sparing tolerance, although there is also a need to take inherent patient
      characteristics into consideration. 

PMID- 26289305
TI  - Educational inequalities in health expectancy during the financial crisis in
      Denmark.
AB  - OBJECTIVES: To investigate educational differentials in health expectancy among
      50-year-old Danes before and during the financial crisis. METHODS: Nationwide
      register data on mortality were combined with data from SHARE surveys in
      2006/2007 and 2010/2011 to estimate disability-free life expectancy (DFLE) and
      expected lifetime in self-rated good health by educational level. RESULTS: The
      difference in life expectancy between 50-year-old men and women with high and low
      educational levels increased by 0.3 and 0.8 years, respectively. The overall
      educational differentials in DFLE did not change much for women, whereas for men
      the tendency was that DFLE increased for those with high educational level and
      decreased for those with less education ascending the difference by almost 2
      years (from 5.9 to 7.8 years), although the difference was not statistically
      significant. The educational disparity in expected lifetime in self-rated good
      health increased by 1.3 years for men and 1.2 years for women. CONCLUSIONS: The
      social inequality in DFLE for men and expected lifetime in self-rated good health
      for both genders increased slightly during the short period. The financial crisis
      did not seem to indicate a change in the persistent trend of the widening social
      gap.

PMID- 26289306
TI  - Patient Specific Factors Influencing Adherence to INR Monitoring.
AB  - OBJECTIVE: The specific reasons underlying nonadherence to monitoring the
      international normalized ratio (INR) from the patient's perspective have not been
      formally studied. Understanding why patients do or do not adhere has the
      potential to reveal useful targets for improving adherence to INR monitoring or
      alternative treatment strategies. The objective of this study was to gain further
      insight into INR monitoring nonadherence from the patient's perspective. METHODS:
      This qualitative study was conducted among members of Kaiser Permanente Colorado;
      patients were characterized as adherent or nonadherent and recruited from the
      Clinical Pharmacy Anticoagulation and Anemia Service to participate in an
      individual interview. Qualitative analysis was performed to identify emerging
      themes using an inductive approach. Demographic data were summarized using
      descriptive statistics. RESULTS: Patients were primarily white and employed with
      a mean age of 61.3 years. Perspectives and experiences were similar for all
      interviewed patients regardless of classification as adherent or nonadherent. The
      most common themes were the desire for INR monitoring to be inexpensive,
      convenient, and accessible; finding reassurance with INR monitoring; and a
      preference for interacting with the same group of prescribers, pharmacists, and
      phlebotomists. CONCLUSIONS: The following strategies to improve adherence to INR
      testing are suggested: (i) assign anticoagulation providers to work with the same
      patients consistently; (ii) provide formal INR reminders; (iii) avoid harsh
      language or lecturing patients following missed INR tests; (iv) reinforce the
      clinical and psychological utility of INR results; and (v) facilitate access to
      INR testing. Adopting these strategies into clinical practice can support the
      patient-clinician relationship and empower patients to be more engaged in their
      health care.

PMID- 26289307
TI  - The beta-Lactams Strike Back: Ceftazidime-Avibactam.
AB  - Gram-negative resistance has reached a crucial point, with emergence of pathogens
      resistant to most or all available antibiotics. Ceftazidime-avibactam is a newly
      approved agent combining ceftazidime and a novel beta-lactamase inhibitor with
      activity against multidrug-resistant gram-negative bacteria. Avibactam has
      increased potency and expanded spectrum of inhibition of class A and C beta
      lactamases relative to available beta-lactamase inhibitors, including extended
      spectrum beta-lactamases, AmpC, and Klebsiella pneumoniae carbapenemase (KPC)
      enzymes. Avibactam expands ceftazidime's spectrum of activity to include many
      ceftazidime- and carbapenem-resistant Enterobacteriaceae and Pseudomonas
      aeruginosa. Early clinical data indicate that ceftazidime-avibactam is effective
      and well tolerated in patients with complicated urinary tract infections (cUTIs)
      and complicated intraabdominal infections (cIAI). In a phase II trial of patients
      with cUTIs, ceftazidime-avibactam produced similar rates of clinical and
      microbiologic success compared with imipenem-cilastatin (70.5% and 71.4%
      microbiologic success rates, respectively). Likewise, patients receiving
      ceftazidime-avibactam plus metronidazole in a phase II study of patients with
      cIAI had similar response rates to those receiving meropenem (91.2% and 93.4%
      clinical success rates, respectively). Based on available in vitro, in vivo, and
      phase II trial data, as well as preliminary phase III trial results in
      ceftazidime-resistant, gram-negative cUTI and cIAI, ceftazidime-avibactam
      received U.S. Food and Drug Administration approval for treatment of cUTI,
      including pyelonephritis, and cIAI, in combination with metronidazole, in adult
      patients with limited or no alternative treatment options. The approved dosage,
      ceftazidime 2 g-avibactam 0.5 g administered as a 2-hour infusion every 8 hours,
      was selected based on pharmacodynamic analysis and available clinical data. This
      dosage is under further investigation in patients with cUTI, cIAI, and nosocomial
      or ventilator-associated pneumonia. The current body of evidence suggests that
      ceftazidime-avibactam is a promising addition to our therapeutic armamentarium
      with potential to answer an urgent unmet medical need. Further data in highly
      resistant gram-negative infections, particularly those caused by KPC-producing
      Enterobacteriaceae, are needed. As it is introduced into clinical use, careful
      stewardship and rational use are essential to preserve ceftazidime-avibactam's
      potential utility. 

PMID- 26289308
TI  - Prevalence, Pathophysiology, and Management of Androgen Deficiency in Men with
      Metabolic Syndrome, Type 2 Diabetes Mellitus, or Both.
AB  - The prevalence of type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS)
      has increased in the United States over the past 40 years. These conditions, long
      linked with many cardiovascular complications, have recently been linked with
      androgen or testosterone deficiency in men. Several pathophysiologic hypotheses
      exist regarding this association, with the most widely reported a relationship to
      obesity and insulin resistance. Several randomized trials have confirmed that
      when testosterone replacement therapy is given to patients with T2DM, MetS, or
      both, metabolic parameters such as waist circumference, hemoglobin A1c , and
      systolic blood pressure are significantly reduced by up to 11 cm, 1.9%, and 23 mm
      Hg, respectively. This has not, however, resulted in improved cardiovascular
      outcomes, as evidenced in studies that found increased rates of cardiovascular
      events following testosterone replacement therapy. In this review, we summarize
      the relevant literature regarding the pathophysiology and management of androgen
      deficiency in men with T2DM, MetS, or both. 

PMID- 26289309
TI  - Successful Use of N-Acetylcysteine to Treat Severe Hepatic Injury Caused by a
      Dietary Fitness Supplement.

PMID- 26289310
TI  - Extracorporeal Elimination of Piperacillin/Tazobactam during Molecular Adsorbent
      Recirculating System Therapy.
AB  - Use of the Molecular Adsorbent Recirculating System (MARS) as a liver support
      device continues to grow worldwide. Various components of the MARS circuit remove
      both protein-bound and water-soluble molecules. Little is known about the extent
      of the enhanced clearance mechanisms used in MARS therapy on drug elimination. Of
      particular interest to acute care practitioners is the impact of MARS on
      antibiotic clearance, as suboptimal concentrations of such drugs can negatively
      impact patient outcomes. The properties of piperacillin/tazobactam suggest that
      elimination may be enhanced in the setting of MARS therapy. We describe two cases
      in which this was studied. Piperacillin concentrations were determined at various
      points within the MARS circuit, and patient serum concentrations were reported
      throughout the dosing interval while receiving MARS therapy. Piperacillin
      concentrations in both cases were in excess of the desired goal minimum
      inhibitory concentrations for treatment of gram-negative infections. Use of an
      extended-infusion strategy of piperacillin/tazobactam 3.375 or 4.5 g given every
      8 hours maintained desired serum levels throughout the dosing interval. To our
      knowledge, this is the second published report on the use of
      piperacillin/tazobactam during MARS therapy. These case reports reveal successful
      dosing strategies for patients requiring piperacillin/tazobactam while receiving
      MARS therapy, as well as quantify the influence of individual MARS elements on
      drug extraction. 

PMID- 26289311
TI  - Editorial Note.

PMID- 26289312
TI  - Imaging innate immune responses at tumour initiation: new insights from fish and
      flies.
AB  - Recent imaging studies in genetically tractable and translucent zebrafish and
      Drosophila melanogaster models have opened a window on the earliest stages of
      tumorigenesis, when pre-neoplastic cells first arise in tissues before they
      progress into full-blown cancers. Innate immune cells often find these cells soon
      after they develop, but this efficient surveillance is not always good for the
      host because although immune cells have phagocytic capacity, they can also
      nurture the growing clones of pre-neoplastic cells. We describe these newly
      observed early interactions between immune cells and cancer cells and speculate
      on their potential clinical implications. 

PMID- 26289313
TI  - Immunotherapy: Engineering a sTrategy for multiple myeloma.

PMID- 26289317
TI  - Correction.

PMID- 26289318
TI  - A Culturally Adapted Smoking Cessation Intervention for Korean Americans:
      Preliminary Findings.
AB  - Korean Americans have the highest smoking rate within the Asian American
      population. This study examined the feasibility and acceptability of a culturally
      adapted telephone cessation intervention for Korean Americans. Participants were
      recruited from advertisements on a Korean radio station channel in New York City.
      All received a combination of telephone cessation counseling and nicotine
      patches. Thirty-one (2 women and 29 men) participated in the study. At 3-month
      follow-up, 14 (45.2%) reported 7-day point prevalence abstinence and 13 (41.9%)
      achieved 3-month prolonged abstinence. Except for two who lived alone, self
      reported abstinence was corroborated by a family member. The findings point to
      the direction that a nationally centralized Korean-language quitline service
      should be established to help Korean Americans quit smoking. Furthermore, the
      service should be adapted at a deep level of the culture.

PMID- 26289315
TI  - The dynamic control of signal transduction networks in cancer cells.
AB  - Cancer is often considered a genetic disease. However, much of the enormous
      plasticity of cancer cells to evolve different phenotypes, to adapt to
      challenging microenvironments and to withstand therapeutic assaults is encoded by
      the structure and spatiotemporal dynamics of signal transduction networks. In
      this Review, we discuss recent concepts concerning how the rich signalling
      dynamics afforded by these networks are regulated and how they impinge on cancer
      cell proliferation, survival, invasiveness and drug resistance. Understanding
      this dynamic circuitry by mathematical modelling could pave the way to new
      therapeutic approaches and personalized treatments. 

PMID- 26289319
TI  - Assisted dying: legal ambiguity lets down families as well as patients.

PMID- 26289316
TI  - Lipoxin and resolvin biosynthesis is dependent on 5-lipoxygenase activating
      protein.
AB  - Resolution of acute inflammation is an active process coordinated by proresolving
      lipid mediators (SPMs) such as lipoxins (LXs) and resolvins (Rvs), which are
      formed by the concerted action of 2 lipoxygenases (LOs). Because the exact
      molecular mechanisms of SPM biosynthesis are not completely understood, we aimed
      to investigate LX and D-type Rv formation in human leukocytes and HEK293T cells
      overexpressing leukotriene (LT) pathway enzymes. Activity assays in precursor (15
      hydroxyeicosatetraenoic acids, 17-HDoHE)-treated granulocytes [polymorphonuclear
      leukocytes (PMNLs)] showed a strict dependence of LXA4/RvD1 biosynthesis on cell
      integrity, and incubation with recombinant human 5-LO did not lead to LX or Rv
      formation. Pharmacologic inhibition of 5-LO activating protein (FLAP) by MK-886
      inhibited LXA4/RvD1 biosynthesis in precursor-treated PMNLs (drug concentration
      causing 50% inhibition ~ 0.3/0.2 uM), as did knockdown of the enzyme in MM6
      cells, and precursor-treated HEK293T overexpressing 5-LO produced high amounts of
      LXA4 only in the presence of FLAP. In addition, inhibition of cytosolic
      phospholipase A2alpha (cPLA2alpha) interfered with LXA4/RvD1 formation from
      exogenous precursors in PMNLs. Furthermore, inhibition of the LT synthases LTA4
      hydrolase and LTC4 synthase in PMNL/platelet coincubations augmented LXA4 levels.
      These findings show that several enzymes known to be involved in the biosynthesis
      of proinflammatory LTs, such as FLAP and cPLA2alpha, also contribute to LX and Rv
      formation.

PMID- 26289320
TI  - Profiling the sport of stand-up paddle boarding.
AB  - Stand-up paddle boarding (SUP) is a rapidly growing activity where only anecdotal
      evidence exists for its proposed health and fitness benefits. The purpose of this
      study was to profile elite and recreational SUP with respect to anthropometric,
      physiological and musculoskeletal measurements. A total of 30 SUP participants
      (15 recreational, 15 elite) and 15 sedentary controls participated in this study.
      Elite and recreational (rec) SUP participants had significantly lower body fat
      than sedentary (sed) individuals, elite had significantly higher HDL and
      significantly lower triglycerides than other groups during lipid profiling (P >
      0.05). There were significant differences (P > 0.05) between all groups in
      maximal oxygen uptake (elite 43.7, s = 5.89 ml . kg(-1) . min(-1) vs. rec 31.9, s
      = 7.7 ml . kg(-1) . min(-1) vs. sed 20.4, s = 3.7 ml . kg(-1) . min(-1)) and
      anaerobic power outputs (35.7, s = 11.1 W vs. 25.0, s = 11.7 W vs. 13.5, s = 7.1
      W). The elite group displayed significantly longer endurance than the
      recreational and sedentary group in the prone bridge (elite 253.4, s = 67.6 s vs.
      rec 165.6, s = 42.2 s vs. sed 69.7, s = 31.2 s), right-sided bridge (elite 107.9,
      s = 34.0 s vs. recreational 68.2, s = 24.1 s vs. sed 34.6, s = 15.5 s), left
      sided bridge (elite 99.8, s = 24.9 s vs. rec 68.2, s = 27.2 s vs. sed 32.5, s =
      15.2 s) and Biering Sorensen test (elite 148.8, s = 35.4 s vs. rec 127.2, s =
      43.2 s vs. sed 71.1, s = 32.9 s). Elite SUP had significantly better static and
      dynamic postural control when compared to the other groups. This study
      demonstrates the anthropometric, physiological and musculoskeletal values
      representative of elite and recreational SUP. SUP appears to be associated with
      increased levels of aerobic and anaerobic fitness, increased static and dynamic
      balance and a high level of isometric trunk endurance. 

PMID- 26289314
TI  - Glycosylation in cancer: mechanisms and clinical implications.
AB  - Despite recent progress in understanding the cancer genome, there is still a
      relative delay in understanding the full aspects of the glycome and glycoproteome
      of cancer. Glycobiology has been instrumental in relevant discoveries in various
      biological and medical fields, and has contributed to the deciphering of several
      human diseases. Glycans are involved in fundamental molecular and cell biology
      processes occurring in cancer, such as cell signalling and communication, tumour
      cell dissociation and invasion, cell-matrix interactions, tumour angiogenesis,
      immune modulation and metastasis formation. The roles of glycans in cancer have
      been highlighted by the fact that alterations in glycosylation regulate the
      development and progression of cancer, serving as important biomarkers and
      providing a set of specific targets for therapeutic intervention. This Review
      discusses the role of glycans in fundamental mechanisms controlling cancer
      development and progression, and their applications in oncology. 

PMID- 26289321
TI  - Multimodality Evaluation of the Right Ventricle: An Updated Review.
AB  - The assessment of the volumes, function, and mechanics of the right ventricle
      (RV) is very challenging because of the anatomical complexity of the RV. Because
      RV structure, function, and deformation are very important predictors of
      cardiovascular morbidity and mortality in patients with heart failure, pulmonary
      hypertension, congenital heart disease, or arrhythmogenic RV cardiomyopathy, it
      is of great importance to use an appropriate imaging modality that will provide
      all necessary information. In everyday clinical practice, 2-dimensional
      echocardiography (2DE) represents a method of first choice in RV evaluation.
      However, cardiac magnetic resonance (CMR) remained the gold standard for RV
      assessment. The development of new imaging tools, such as 3-dimensional
      echocardiography (3DE), provided reliable data, comparable with CMR, and opened a
      completely new era in RV imaging. So far, 3DE has shown good results in
      determination of RV volumes and systolic function, and there are indications that
      it will also provide valuable data about 3-dimensional RV mechanics, similar to
      CMR. Two-dimensional echocardiography-derived strain is currently widely used for
      the assessment of RV deformation, which has been proven to be a more significant
      predictor of functional capacity and survival than CMR-derived RV ejection
      fraction. The purpose of this review is to summarize currently available data
      about RV structure, function, and mechanics obtained by different imaging
      modalities, primarily 2DE and 3DE, and their comparison with CMR and cardiac
      computed tomography. 

PMID- 26289322
TI  - Does school health and home economics education influence adults' food knowledge?
AB  - Home economics and health teachers are to be found in many parts of the world.
      They teach students about food in relation to its nutritional, safety and
      environmental properties. The effects of such teaching might be expected to be
      reflected in the food knowledge of adults who have undertaken school education in
      these areas. This study examined the food knowledge associations of school home
      economics and health education among Australian adults. Two separate online
      surveys were conducted nationwide among 2022 (November 2011) and 2146 Australian
      adults (November-December 2012). True/false and multiple choice questions in both
      surveys were used to assess nutrition, food safety and environmental knowledge.
      Knowledge scores were constructed and compared against respondents' experience of
      school health or home economics education via multiple regression analyses. The
      results from both studies showed that home economics (and similar) education was
      associated with higher levels of food knowledge among several age groups. The
      associations of home economics education with food knowledge differed across
      several Australian states and recall of home economics themes differed across the
      age groups. These findings suggest that home economics education may bring about
      long-lasting learning of food knowledge. Further research is required, however,
      to confirm the findings and to test the causal influence of home economics
      education on adults' food knowledge.

PMID- 26289324
TI  - Development and application of an indicator assessment tool for measuring health
      services accreditation programs.
AB  - BACKGROUND: Hospital accreditation programs are internationally widespread and
      consume increasingly scarce health resources. However, we lack tools to
      consistently identify suitable indicators to assess and monitor accreditation
      outcomes. We describe the development and validation of such a tool. RESULTS:
      Using Australian accreditation standards as our reference point we: reviewed the
      research evidence for potential indicators; looked for links with existing
      external indicators; and assessed relevant state and federal policies. We
      allocated provisional scores, on a five point Likert scale, to the five
      accountability criteria in the tool: research; accuracy; proximity; no adverse
      effects; and specificity. An expert panel validated the use of the purpose
      designed indicator assessment tool. The panel identified hand hygiene compliance
      rates as a suitable process indicator, and hospital acquired Staphylococcus
      aureus infection (SAB) rates as an outcome indicator, with the hypothesis that
      improved hand hygiene compliance rates and lower SAB rates would correlate with
      accreditation performance. CONCLUSIONS: This new tool can be used to identify,
      analyse, and compare accreditation indicators. Using infection control indicators
      such as hand hygiene compliance and SAB rates to measure accreditation
      effectiveness has merit, and their efficacy can be determined by comparing
      accreditation scores with indicator outcomes. To verify the tool as a robust
      instrument, testing is needed in other health service domains, both in Australia
      and internationally. This tool provides health policy makers with an important
      means for assessing the accreditation programs which form a critical part of the
      national patient safety and quality framework.

PMID- 26289323
TI  - Association of p53 rs1042522, MDM2 rs2279744, and p21 rs1801270 polymorphisms
      with retinoblastoma risk and invasion in a Chinese population.
AB  - Single nucleotide polymorphisms (SNPs) of p53 rs1042522, MDM2 rs2279744 and p21
      rs1801270, all in the p53 pathway, which plays a crucial role in DNA damage and
      genomic instability, were reported to be associated with cancer risk and
      pathologic characteristics. This case-control study was designed to analyse the
      association between these SNPs and retinoblastoma (RB) in a Chinese Han
      population. These SNPs in 168 RB patients and 185 adult controls were genotyped
      using genomic DNA from venous blood. No significant difference was observed in
      allele or genotypic frequencies of these SNPs between Chinese RB patients and
      controls (all P > 0.05). However, the rs1042522 GC genotype showed a protective
      effect against RB invasion, as demonstrated by event-free survival (HR = 0.53, P
      = 0.007 for GC versus GG/CC). This effect was significant for patients with a lag
      time >1 month and no pre-enucleation treatment (P = 0.007 and P = 0.010,
      respectively), indicating an interaction between p53 rs1042522 and clinical
      characteristics, including lag time and pre-enucleation treatment status. Thus,
      the rs1042522 SNP may be associated with RB invasion in the Han Chinese
      population; however, further large and functional studies are needed to assess
      the validity of this association. 

PMID- 26289326
TI  - Preparation of gasification feedstock from leafy biomass.
AB  - Dried leaves are a potential source of energy although these are not commonly
      used beside to satisfy daily energy demands in rural areas. This paper aims at
      preparing a leafy biomass feedstock in the form of briquettes which can be
      directly used for combustion or to extract the combustible gas using a gasifier.
      Teak (Tectona grandis) and rubber (Hevea brasiliensis) leaves are considered for
      the present study. A binder-assisted briquetting technique with tapioca starch as
      binder is adopted. Properties of these leafy biomass briquettes such as moisture
      content, calorific value, compressive strength, and shatter index are determined.
      From the study, briquettes with biomass-to-binder ratio of 3:5 are found to be
      stable. Higher mass percentage of binder is considered for preparation of
      briquettes due to the fact that leafy biomasses do not adhere well on
      densification with lower binder content. Ultimate analysis test is conducted to
      analyze the gasification potential of the briquettes. Results show that the leafy
      biomass prepared from teak and rubber leaves has calorific values of 17.5 and
      17.8 MJ/kg, respectively, which are comparable with those of existing biomass
      feedstock made of sawdust, rice husk, and rice straw. 

PMID- 26289325
TI  - Evolution of the unspliced transcriptome.
AB  - BACKGROUND: Despite their abundance, unspliced EST data have received little
      attention as a source of information on non-coding RNAs. Very little is know,
      therefore, about the genomic distribution of unspliced non-coding transcripts and
      their relationship with the much better studied regularly spliced products. In
      particular, their evolution has remained virtually unstudied. RESULTS: We
      systematically study the evidence on unspliced transcripts available in EST
      annotation tracks for human and mouse, comprising 104,980 and 66,109 unspliced
      EST clusters, respectively. Roughly one third of these are located totally inside
      introns of known genes (TINs) and another third overlaps exonic regions (PINs).
      Eleven percent are "intergenic", far away from any annotated gene. Direct
      evidence for the independent transcription of many PINs and TINs is obtained from
      CAGE tag and chromatin data. We predict more than 2000 3'UTR-associated RNA
      candidates for each human and mouse. Fifteen to twenty percent of the unspliced
      EST cluster are conserved between human and mouse. With the exception of TINs,
      the sequences of unspliced EST clusters evolve significantly slower than genomic
      background. Furthermore, like spliced lincRNAs, they show highly tissue-specific
      expression patterns. CONCLUSIONS: Unspliced long non-coding RNAs are an
      important, rapidly evolving, component of mammalian transcriptomes. Their
      analysis is complicated by their preferential association with complex
      transcribed loci that usually also harbor a plethora of spliced transcripts.
      Unspliced EST data, although typically disregarded in transcriptome analysis, can
      be used to gain insights into this rarely investigated transcriptome component.
      The frequently postulated connection between lack of splicing and nuclear
      retention and the surprising overlap of chromatin-associated transcripts suggests
      that this class of transcripts might be involved in chromatin organization and
      possibly other mechanisms of epigenetic control.

PMID- 26289327
TI  - Fungal community dynamics and driving factors during agricultural waste
      composting.
AB  - This study was conducted to identify the driving factors behind fungal community
      dynamics during agricultural waste composting. Fungal community abundance and
      structure were determined by quantitative PCR and denaturing gradient gel
      electrophoresis analysis combined with DNA sequencing. The effects of physico
      chemical parameters on fungal community abundance and structure were evaluated by
      least significant difference tests and redundancy analysis. The results showed
      that Cladosporium bruhnei, Hanseniaspora uvarum, Scytalidium thermophilum,
      Tilletiopsis penniseti, and Coprinopsis altramentaria were prominent during the
      composting process. The greatest variation in the distribution of fungal
      community structure was statistically explained by pile temperature and total
      organic carbon (TOC) (P < 0.05). A significant amount of the variation (74.6 %)
      was explained by these two parameters alone. Fungal community abundance was found
      to be significantly related to pH, while pH was significantly influenced by pile
      temperature and nitrate levels (P < 0.05), and these parameters were found to be
      the most likely to influence or be influenced by the fungal community during
      composting.

PMID- 26289328
TI  - Blood concentrations and risk assessment of persistent organochlorine compounds
      in newborn boys in Turkey. A pilot study.
AB  - Even early life in utero cannot provide a safe place for newborns. The first
      acquaintance with chemicals takes place in utero and/or with mother's milk after
      delivery. Besides legislations and bans to persistent organic pollutants (POPs),
      these chemicals are still affecting the general population especially the
      children as they are one of the populations most susceptible to chemicals, and
      also the health problems may arise in the future. Our objective is to collect the
      first data in newborns in Turkey to determine baseline levels of POPs in the
      general population and estimate the potential cancer risk related to exposure.
      Twenty-nine organochlorine pesticides (OCPs) and 18 polychlorinated biphenyl
      (PCB) congeners in blood samples of newborn boys (0-1 month old) who were born in
      Istanbul, Turkey, in 2010-2012 were evaluated with high-resolution gas
      chromatography-high-resolution mass spectrometry (HRGC/HRMS). Results for
      analyzed chlorinated compounds are as follows: hexachlorocyclohexane (SigmaHCH)
      1828 +/- 3650 pg/g lipid, dichlorodiphenyltrichloroethane (SigmaDDT) 10,000 +/-
      15,398 pg/g lipid, and SigmaPCB 1068 +/- 1823 pg/g lipid. 4,4'-DDT, 4,4'
      dichlorodiphenyldichloroethylene (4,4'-DDE), hexachlorobenzene, and PCB 138 and
      153 are the major contaminants. New POPs as lindane 61 +/- 268 pg/g lipid,
      pentachlorobenzene 13 +/- 74 pg/g lipid, and endosulfan 29 +/- 106 pg/g lipid are
      also detected in blood. Estimated total risk for lifetime PCB exposure is less
      than 1 * 10(-5), an acceptable risk. Blood concentration levels will be important
      base data in the assessment of health concerns of newborns as well as for studies
      about how endocrine disruptors affect humans.

PMID- 26289329
TI  - The use of food waste-based diets and Napier grass to culture grass carp: growth
      performance and contaminants contained in cultured fish.
AB  - The present study used commercial feeds, food waste feeds, Napier grass, and
      mixed feeds (food waste feed to Napier grass ratio, 1:10) to feed grass carp
      (Ctenopharyngodon idellus). The results indicated that grass carp fed with food
      waste feeds and mix feeds achieved growth performance (based on specific growth
      rate and feed conversion ratio) that was similar to commercial feeds (p > 0.05).
      Concentrations of metalloid/metals in food waste feeds and polycyclic aromatic
      hydrocarbons (PAHs) in Napier grass were relatively higher than other types of
      fish feeds (p < 0.05). However, most of the metalloid/metals and PAH levels in
      fish fed with four types of fish feeds were not significantly different (p >
      0.05). These findings show that food waste feeds are suitable for using in the
      production of fish feed and Napier grass can be served as supplemental feeds for
      grass carp, and hence reducing the production cost. 

PMID- 26289330
TI  - Accelerated solvent extraction (ASE) for purification and extraction of silicone
      passive samplers used for the monitoring of organic pollutants.
AB  - Silicone passive samplers have gained an increasing attention as single-phased,
      practical and robust samplers for monitoring of organic contaminants in the
      aquatic environment in recent years. However, analytical challenges arise in
      routine application during the extraction of analytes as silicone oligomers are
      co-extracted and interfere severely during chemical analyses (e.g. gas
      chromatographic techniques). In this study, we present a fast, practical pre
      cleaning method for silicone passive samplers applying accelerated solvent
      extraction (ASE) for the removal of silicone oligomers prior to the water
      deployment (hexane/dichloromethane, 100  degrees C, 70 min). ASE was also shown
      to be a very fast (10 min) and efficient extraction method for non-polar
      contaminants (non-exposed PRC recoveries 66-101 %) sampled by the silicone
      membrane. For both applications, temperature, extraction time and the solvent
      used for ASE have been optimized. Purification of the ASE extract was carried out
      by silica gel and high-pressure liquid size exclusion chromatography (HPLC-SEC).
      The silicone oligomer content was checked by total reflection X-ray fluorescence
      spectroscopy (TXRF) in order to confirm the absence of the silicone oligomers
      prior to analysis of passive sampler extracts. The established method was applied
      on real silicone samplers from the North- and Baltic Sea and showed no matrix
      effects during analysis of organic pollutants. Internal laboratory standard
      recoveries were in the same range for laboratory, transport and exposed samplers
      (85-126 %).

PMID- 26289331
TI  - Chemical speciation and ecological risk assessment of arsenic in marine sediments
      from Izmir Bay (Eastern Aegean Sea).
AB  - Total arsenic, arsenic(III) and (V), Fe, and Mn were measured in 17 surface
      sediment samples from Izmir Bay. The concentrations and ecological risk of As
      were characterized in the sediment affected by urban and agricultural activities.
      Total As ranged from 8.87 to 28.3 MUg g(-1) dry weight (96.5-99.9 % as inorganic
      As). Distribution of total As and total As/Fe followed a different trend in
      sediments at all sampling sites. Arsenite (As(III)) was the most dominant form
      followed by As(V), while organic arsenic represented a minor constituent (0.03 to
      3.49 %). The highest concentration of total As was observed at Gediz River
      estuary and exceeded lower threshold value (threshold effects level (TEL)). Due
      to the biological reduction of As(V) and abundance of Fe (oxyhydr)oxides in the
      sediments, most inorganic As in the Izmir Bay was present as As(III). Besides,
      the levels of As were >TEL and <PEL at all stations, suggesting that As may not
      currently impose ecologically dangerous impacts in the sedimentary environment of
      Izmir Bay. At all sampling sites in the Izmir Bay, nevertheless, natural sources
      of As need to be considered to explain the distribution patterns. This work
      highlights the need for arsenic speciation analysis to accurately assess
      potential toxicity of marine resources and provides a crucial baseline to assess
      the impact of future development within this region.

PMID- 26289332
TI  - Antioxidant enzymes activities of Burkholderia spp. strains-oxidative responses
      to Ni toxicity.
AB  - Increased agriculture production associated with intense application of
      herbicides, pesticides, and fungicides leads to soil contamination worldwide.
      Nickel (Ni), due to its high mobility in soils and groundwater, constitutes one
      of the greatest problems in terms of environmental pollution. Metals, including
      Ni, in high concentrations are toxic to cells by imposing a condition of
      oxidative stress due to the induction of reactive oxygen species (ROS), which
      damage lipids, proteins, and DNA. This study aimed to characterize the Ni
      antioxidant response of two tolerant Burkholderia strains (one isolated from
      noncontaminated soil, SNMS32, and the other from contaminated soil, SCMS54), by
      measuring superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR),
      and glutathione S-transferase (GST) activities. Ni accumulation and bacterial
      growth in the presence of the metal were also analyzed. The results showed that
      both strains exhibited different trends of Ni accumulation and distinct
      antioxidant enzymes responses. The strain from contaminated soil (SCMS54)
      exhibited a higher Ni biosorption and exhibited an increase in SOD and GST
      activities after 5 and 12 h of Ni exposure. The analysis of SOD, CAT, and GR by
      nondenaturing PAGE revealed the appearance of an extra isoenzyme in strain SCMS54
      for each enzyme. The results suggest that the strain SCMS54 isolated from
      contaminated soil present more plasticity with potential to be used in soil and
      water bioremediation. 

PMID- 26289333
TI  - Emissions of NO and N2O in wetland microcosms for swine wastewater treatment.
AB  - Nitric oxide (NO) and nitrous oxide (N2O) emitted from wetland systems contribute
      an important proportion to the global warming effect. In this study, four wetland
      microcosms vegetated with Myriophyllum elatinoides (WM), Alternanthera
      philoxeroides (WA), Eichhornia crassipes (WE), or without vegetation (NW) were
      compared to investigate the emissions of NO and N2O during nitrogen (N) removal
      process when treating swine wastewater. After 30-day incubation, TN removal rates
      of 96.4, 74.2, 97.2, and 47.3 % were observed for the WM, WA, WE, and NW
      microcosms, respectively. Yet, no significant difference was observed in WM and
      WE (p > 0.05). The average NO and N2O emissions in WE was significantly higher
      than those in WM, WA, and NW (p < 0.05). In addition, the emission of N2O in WE
      accounted for 2.10 % of initial TN load and 2.17 % of the total amount of TN
      removal, compared with less than 1 % in the other microcosms. These findings
      indicate that wetland vegetated with M. elatinoides may be an optimal system for
      swine wastewater treatment, based on its higher removal of N and lower emissions
      of NO and N2O.

PMID- 26289334
TI  - Cadmium exposure and the risk of breast cancer in Chaoshan population of
      southeast China.
AB  - Recently, there is increasing evidence indicating a link between cadmium exposure
      and human breast cancer. This study was aimed to explore the relationship between
      blood cadmium burden and the risk of breast cancer in Chaoshan women with no
      occupational exposure. Blood cadmium levels (BCLs) were determined in whole blood
      of 186 breast cancer cases and 139 controls. Basic clinical data and information
      of age, occupation, blood types, family cancer history, and disease history, as
      well as other demographic characteristics were collected from medical records.
      BCLs were detected by graphite-furnace atomizer absorption spectrophotometer
      (GFAAS). BCLs and proportions of BCLs over 3 MUg/L between cases and controls
      were compared. The relationships between BCLs and breast cancer were explored by
      comparing BCL differences between/among different characteristics of investigated
      factors. In addition, BCLs within cases were also compared in relation to the
      disease clinical stages, tumor-node-metastasis (TNM) stages, and estrogen
      receptor (ER), progesterone receptor (PR), and Cerb-B2 expressions. The breast
      cancer patients had a higher median concentration of blood cadmium (2.28,
      interquartile range 1.57-3.15 MUg/L) than the controls (1.77, 1.34-2.57 MUg/L; P
      = 0.001). The proportion of BCLs over 3 MUg/L was 2.35 times higher in the breast
      cancer cases than that of the controls after adjusting for age. Cadmium tends to
      accumulate in the human body with age and body mass index (BMI) but not
      associates with type of job, family history, disease history, and other
      investigated characters. With the increase of clinical stages and T and M stages,
      the BCLs in the breast cancer cases also increased. BCLs were positively
      associated with Cerb-B2 expression (r = 0.152, P = 0.038) but not significantly
      associated with ER and PR expressions. The data obtained show that cadmium
      concentration is significantly higher in blood of breast cancer patients in
      comparison to healthy controls. Cadmium seems to be a risk factor of breast
      cancer, and high cadmium exposure was observed in advanced stages of this
      disease, which indicates that it may promote the development of breast cancer.

PMID- 26289335
TI  - Remobilization of trace metals from contaminated marine sediment in a simulated
      dynamic environment.
AB  - In this study, release and redistribution of sediment bound trace metals due to
      resuspension were investigated by a lid-driven elongated annular flume (LEAF).
      The total suspended particulate matters (SPMs) increased significantly in
      quantity with the raised resuspension energies and varied distinctively in
      particle size and mineral composition. Except for Cu, Ni, Cd, Pb, and Zn showed
      an increase in dissolved phase as the resuspension energy increased. Relatively
      low Cu was observed in dissolved phase whereas it owned the highest original
      concentration in the sediment. This is primarily due to the very low solubility
      of Cu sulfide. In comparison to sediment, all metals were evidently enriched in
      SPMs which primarily contributed to the much more fine particles (silt/clay
      fraction) contained in the SPMs. Metals enrichment followed the Irving-Williams
      order of complex stability. However, metals content varied indistinctively in the
      SPMs among the three selected resuspension levels. The distribution coefficients
      (K d) exhibited opposite trend with the increasing resuspension level with the
      exception of Cu. It indicated that physical and chemical characters of sediment
      such as grain composition, Fe/Mn, and organic matter content may also act as
      major factors in the release of metals and control their phase distribution in
      the water column. 

PMID- 26289336
TI  - Study and health risk assessment of the occurrence of iron and manganese in
      groundwater at the terminal of the Xiangjiang River.
AB  - The pollution of the surface water in the Xiangjiang watershed in China has
      received much attention, whereas the groundwater conditions in the area have long
      been ignored. This study investigates the occurrence of Fe and Mn in the
      groundwater of Chengxi Town located at the terminal of the Xiangjiang River. The
      study area was monitored for an entire year. Thereafter, the associated health
      risks were identified. Results showed that approximately 81 and 73 % of the
      measured samples exceeded the limits for Fe and Mn in Chinese drinking water,
      respectively. pH level was found to be negatively correlated with the
      concentrations of Fe and Mn in the groundwater in the study area. The occurrence
      of Fe in the groundwater showed significant seasonal fluctuations and was
      possibly affected by the change in environment conditions within the aquifer. By
      contrast, Mn remained relatively stable in most of the area during the whole
      year. Overall, no health threats for adults and children in the study area were
      determined according to the low health index values. Nevertheless, research
      attention and the implementation of relevant measures are needed for certain
      villages with exceptionally high Mn concentrations in the groundwater.

PMID- 26289337
TI  - Distribution, accumulation profile, and risk assessment of polybrominated
      diphenyl ethers in sediment from lake and river systems in Hanoi Metropolitan
      Area, Vietnam.
AB  - Concentrations of seven polybrominated diphenyl ethers (PBDEs) congeners were
      determined in surface sediments collected from several rivers and lakes in Hanoi,
      the capital city of Vietnam, to understand the status of background
      contamination, accumulation pattern, sources, and toxic implications for benthic
      organisms. Total PBDE concentrations in all sediment samples ranged from 0.03 to
      17.5 ng/g dry weight (mean 1.33 ng/g dry wt). The most predominant congeners were
      BDE-47 and BDE-99, which comprised 30 and 25 % of total PBDE concentrations,
      respectively. Results from statistical analysis indicated that the potential
      sources of PBDEs of sediments in Hanoi may come from penta-BDE and octa-BDE
      mixtures. Risk quotients of PBDEs in sediments were also calculated for a benthic
      species, ranged from 2.12 * 10-6 - 1.60 * 10-2, and were markedly lower than
      threshold value for occurrence of any ecotoxicological risk. This study provides
      some of the most comprehensive data on the occurrence of PBDEs in sediments from
      lake and river systems in Vietnam.

PMID- 26289338
TI  - Dolomite application to acidic soils: a promising option for mitigating N2O
      emissions.
AB  - Soil acidification is one of the main problems to crop productivity as well as a
      potent source of atmospheric nitrous oxide (N2O). Liming practice is usually
      performed for the amelioration of acidic soils, but the effects of dolomite
      application on N2O emissions from acidic soils are still not well understood.
      Therefore, a laboratory study was conducted to examine N2O emissions from an
      acidic soil following application of dolomite. Dolomite was applied to acidic
      soil in a factorial design under different levels of moisture and nitrogen (N)
      fertilizer. Treatments were as follows: dolomite was applied as 0, 1, and 2 g kg(
      1) soil (named as CK, L, and H, respectively) under two levels of moisture [i.e.,
      55 and 90 % water-filled pore space (WFPS)]. All treatments of dolomite and
      moisture were further amended with 0 and 200 mg N kg(-1) soil as (NH4)2SO4. Soil
      properties such as soil pH, mineral N (NH4 (+)-N and NO3 (-)-N), microbial
      biomass carbon (MBC), dissolved organic carbon (DOC), and soil N2O emissions were
      analyzed throughout the study period. Application of N fertilizer rapidly
      increased soil N2O emissions and peaked at 0.59 MUg N2O-N kg(-1) h(-1) under 90 %
      WFPS without dolomite application. The highest cumulative N2O flux was 246.32 MUg
      N2O-N kg(-1) under 90 % WFPS without dolomite addition in fertilized soil.
      Addition of dolomite significantly (p <= 0.01) mitigated N2O emissions as soil pH
      increased, and H treatment was more effective for mitigating N2O emissions as
      compared to L treatment. The H treatment decreased the cumulative N2O emissions
      by up to 73 and 67 % under 55 and 90 % WFPS, respectively, in fertilized soil,
      and 60 and 68 % under 55 and 90 % WFPS, respectively, in unfertilized soil when
      compared to those without dolomite addition. Results demonstrated that
      application of dolomite to acidic soils is a promising option for mitigating N2O
      emissions.

PMID- 26289339
TI  - Mobilization and distribution of lead originating from roof dust and wet
      deposition in a roof runoff system.
AB  - In this research, the mobilization and distribution of lead originating in roof
      dust and wet deposition were investigated within a roof dust-rooftop-runoff
      system. The results indicated that lead from roof dust and wet deposition showed
      different transport dynamics in runoff system and that this process was
      significantly influenced by the rainfall intensity. Lead present in the roof dust
      could be easily washed off into the runoff, and nearly 60 % of the total lead
      content was present in particulate form. Most of the lead from the roof dust was
      transported during the late period of rainfall; however, the lead concentration
      was higher for several minutes at the rainfall beginning. Even though some of the
      lead from wet deposition, simulated with a standard isotope substance, was
      adsorbed onto adhered roof dust and/or retained on rooftop in runoff system, most
      of it (50-82 %) remained as dissolved lead in the runoff for rainfall events of
      varying intensity. Regarding the distribution of lead in the runoff system, the
      results indicated that it could be carried in the runoff in dissolved and
      particulate form, be adsorbed to adhered roof dust, or remain on the rooftop
      because of adsorption to the roof material. Lead from the different sources
      showed different distribution patterns that were also related to the rainfall
      intensity. Higher rainfall intensity resulted in a higher proportion of lead in
      the runoff and a lower proportion of lead remaining on the rooftop.

PMID- 26289341
TI  - Exploring a new method for deriving the monetary value of a QALY.
AB  - Several studies have sought to determine the monetary value of health gains
      expressed as quality adjusted life years (QALYs) gained, predominantly using
      willingness to pay approaches. However, willingness to pay has a number of
      recognized problems, most notably its insensitivity to scope. This paper presents
      an alternative approach to estimate the monetary value of a QALY, which is based
      on the time trade-off method. Moreover, it presents the results of an online
      study conducted in the Netherlands exploring the feasibility of this novel
      approach. The results seem promising, but also highlight a number of
      methodological problems with this approach, most notably nontrading and the
      elicitation of negative values. Additional research is necessary to try to
      overcome these problems and to determine the potential of this new approach. 

PMID- 26289342
TI  - Evaluating the Impact of a Pharmacist-Led Antiretroviral Stewardship Program on
      Reducing Drug Interactions in HIV-Infected Patients.
AB  - PURPOSE: To compare the number of antiretroviral-related clinically significant
      drug-drug interactions (CSDDIs) occurring in hospitalized patients that were
      intervened upon before and after Antiretroviral Stewardship Program (ARVSP)
      expansion and to classify the interventions made to prevent errors. METHODS: A
      retrospective chart review of adult patients treated with antiretroviral therapy
      (ART) and who were hospitalized from September 2012 to February 2013. A CSDDI was
      defined as requiring an alternative therapy, dose adjustment, or schedule
      modification. Findings were compared to a prior study. RESULTS: A total of 185
      admissions were included and 76 CSDDIs were identified, 19 (25%) occurred after
      ART approval. The percentages of CSDDIs that occurred after ART approval and were
      intervened upon before and after ARVSP expansion were 43% and 95%, respectively
      (P<.001). An additional 80 other interventions were made by the ARVSP.
      CONCLUSION: An ARVSP is critical in the prevention of CSDDIs and errors to
      improve safety in HIV-infected patients.

PMID- 26289340
TI  - Ductal activation of oncogenic KRAS alone induces sarcomatoid phenotype.
AB  - Salivary duct carcinoma (SDC) is an uncommon, but aggressive malignant tumor with
      a high mortality rate. Herein, we reported the detection of somatic KRAS A146T
      and Q61H mutations in 2 out of 4 (50%) sarcomatoid SDC variants. Transgenic mice
      carrying the human oncogenic KRAS(G12V), which spatiotemporal activation by
      tamoxifen (TAM)-inducible Cre recombinase Ela-CreERT in the submandibular gland
      (SMG) ductal cells, was established and characterized. Visible carcinoma was
      detected as early as day-15 following oncogenic KRAS(G12V) induction alone, and
      these tumors proliferate rapidly with a median survival of 28-days accompanied
      with histological reminiscences to human sarcomatoid SDC variants. Moreover,
      these tumors were resistant to cetuximab treatment despite augmented EGFR
      signaling, attesting its malignancy. Our findings suggest that LGL-KRas(G12V);Ela
      CreERT transgenic mice could serve as a useful preclinical model for
      investigating underlying mechanisms and developing potential therapies. 

PMID- 26289343
TI  - The Effect of Early Initiation of Antiretroviral Therapy in TB/HIV-Coinfected
      Patients: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: The importance of early initiation of antiretroviral therapy (ART)
      for tuberculosis (TB) and HIV-coinfected patients is controversial. We conducted
      a systematic review and meta-analysis to assess the effect of early initiation of
      ART (within 2-4 weeks of TB treatment) on several treatment outcomes among TB/HIV
      coinfected patients. METHOD: A systematic search of clinical trials was performed
      in PubMed, Embase, Google Scholar, Science Direct, Medscape, and the Cochrane
      library. Clinical trials which were published in any language before the last
      date of search (March 31, 2015) were included. The qualities of the studies were
      assessed using criteria from the Cochrane Library. Heterogeneity test was
      conducted to assess the variations among study outcomes. For each study outcome,
      the risk ratio (RR) with 95% confidence interval (CI) was calculated as a measure
      of intervention effect. The Mantel-Haenszel method was used to estimate the RR
      using a fixed-effects model. FINDINGS: A total of 2272 study participants from 6
      trials were included in the meta-analysis. Early ART initiation during TB
      treatment was associated with reduced all-cause mortality (RR = 0.78; 95% CI =
      0.63-0.98) and increased rate of TB-associated immune reconstitution inflammatory
      syndrome (TB-IRIS; RR = 2.19; 95% CI = 1.77- 2.70) and death related to TB-IRIS
      (RR = 6.94; 95% CI = 1.26-38.22). However, the time of ART initiation has no
      association with TB cure rate (RR = 0.99; 95% CI = 0.81-1.07), rate of drug
      toxicity (RR = 1.00; 95% CI = 0.93-1.08), death associated with drug toxicity (RR
      = 0.40; 95% CI = 0.14- 1.16), rate of low viral load (less than 400 copies/mL; RR
      = 1.00; 95% CI = 0.96-1.04), and rate of new AIDS-defining illness (RR = 0.84;
      95% CI = 0.60-1.18). Immunological response in early ART arms of study
      participant in different trials showed a greater or equal response compared with
      late ART arms. CONCLUSION: This systematic review presents conclusive evidence on
      the reduction of all-cause mortality as a result of early initiation of ART.
      However, this study also confirms the high rate of TB-IRIS and death associated
      with it. Operational and implementation research are required to maintain the
      benefit of early ART initiation and proper management of TB-IRIS. Studies on the
      timing of ART in extrapulmonary and multidrug-resistant TB are recommended.

PMID- 26289344
TI  - Integrated tRNA, transcript, and protein profiles in response to steroid hormone
      signaling.
AB  - The accurate and efficient transfer of genetic information into amino acid
      sequences is carried out through codon-anticodon interactions between mRNA and
      tRNA, respectively. In this way, tRNAs function at the interface between gene
      expression and protein synthesis. Whether tRNA levels are dynamically regulated
      and to what degree tRNA abundance influences the cellular proteome remains
      largely unexplored. Here we profile tRNA, transcript and protein levels in
      Drosophila Kc167 cells, a plasmatocyte cell line that, upon treatment with 20
      hydroxyecdysone, differentiates into macrophages. We find that high abundance
      tRNAs associate with codons that are overrepresented in the Kc167 cell proteome,
      whereas tRNAs that are in low supply associate with codons that are
      underrepresented. Ecdysone-induced differentiation of Kc167 cells leads to
      changes in mRNA codon usage in a manner consistent with the developmental
      progression of the cell. At both early and late time points, ecdysone treatment
      concomitantly increases the abundance of tRNAThr(CGU), which decodes a
      differentiation-associated codon that becomes enriched in the macrophage
      proteome. These results together suggest that tRNA levels may provide a
      meaningful regulatory mechanism for defining the cellular proteomic landscape. 

PMID- 26289345
TI  - Expedited quantification of mutant ribosomal RNA by binary deoxyribozyme (BiDz)
      sensors.
AB  - Mutations in ribosomal RNA (rRNA) have traditionally been detected by the primer
      extension assay, which is a tedious and multistage procedure. Here, we describe a
      simple and straightforward fluorescence assay based on binary deoxyribozyme
      (BiDz) sensors. The assay uses two short DNA oligonucleotides that hybridize
      specifically to adjacent fragments of rRNA, one of which contains a mutation
      site. This hybridization results in the formation of a deoxyribozyme catalytic
      core that produces the fluorescent signal and amplifies it due to multiple rounds
      of catalytic action. This assay enables us to expedite semi-quantification of
      mutant rRNA content in cell cultures starting from whole cells, which provides
      information useful for optimization of culture preparation prior to ribosome
      isolation. The method requires less than a microliter of a standard Escherichia
      coli cell culture and decreases analysis time from several days (for primer
      extension assay) to 1.5 h with hands-on time of ~10 min. It is sensitive to
      single-nucleotide mutations. The new assay simplifies the preliminary analysis of
      RNA samples and cells in molecular biology and cloning experiments and is
      promising in other applications where fast detection/quantification of specific
      RNA is required. 

PMID- 26289346
TI  - Association of Lower Fractional Flow Reserve Values With Higher Risk of Adverse
      Cardiac Events for Lesions Deferred Revascularization Among Patients With Acute
      Coronary Syndrome.
AB  - BACKGROUND: The safety of deferring revascularization based on fractional flow
      reserve (FFR) during acute coronary syndrome (ACS) is unclear. We evaluated the
      association of FFR and adverse cardiac events among patients with coronary
      lesions deferred revascularization based on FFR in the setting of ACS versus non
      ACS. METHODS AND RESULTS: The study population (674 patients; 816 lesions) was
      divided into ACS (n=334) and non-ACS (n=340) groups based on the diagnosis when
      revascularization was deferred based on FFR values >0.80 between October 2002 and
      July 2010. The association and interaction between FFR and clinical outcomes was
      evaluated using Cox proportional hazards models within each group (mean follow-up
      of 4.5+/-2.1 years). Subsequent revascularization of a deferred lesion was
      classified as a deferred lesion intervention (DLI), whereas the composite of DLI
      or myocardial infarction (MI) attributed to a deferred lesion was designated as
      deferred lesion failure (DLF). In the non-ACS group, lower FFR values were not
      associated with any increase in adverse cardiac events. In the ACS group, every
      0.01 decrease in FFR was associated with a significantly higher rate of
      cardiovascular death, MI, or DLI (hazard ratio [HR], 1.08; 95% confidence
      interval [CI], 1.03 to 1.12), MI or DLI (HR, 1.09; 95% CI: 1.04 to 1.14), DLF
      (HR, 1.12; 95% CI, 1.06 to 1.18), MI (HR, 1.07; 95% CI, 1.00 to 1.14), and DLI
      (HR, 1.12; 95% CI, 1.06 to 1.18). CONCLUSION: Lower FFR values among ACS patients
      with coronary lesions deferred revascularization based on FFR are associated with
      a significantly higher rate of adverse cardiac events. This association was not
      observed in non-ACS patients.

PMID- 26289348
TI  - Highly photocatalytic TiO2 interconnected porous powder fabricated by sponge
      templated atomic layer deposition.
AB  - A titanium dioxide (TiO2) interconnected porous structure has been fabricated by
      means of atomic layer deposition of TiO2 onto a reticular sponge template. The
      obtained freestanding TiO2 with large surface area can be easily taken out of the
      water to solve a complex separation procedure. A compact and conformal
      nanocoating was evidenced by morphologic characterization. A phase transition, as
      well as production of oxygen vacancies with increasing annealing temperature, was
      detected by x-ray diffraction and x-ray photoelectron spectroscopy, respectively.
      The photocatalytic experimental results demonstrated that the powder with
      appropriate annealing treatment possessed excellent photocatalytic ability due to
      the co-action of high surface area, oxygen vacancies and the optimal crystal
      structure. 

PMID- 26289347
TI  - Population-Based Study of Incidence of Acute Abdominal Aortic Aneurysms With
      Projected Impact of Screening Strategy.
AB  - BACKGROUND: Current abdominal aortic aneurysm (AAA) screening in men age 65 might
      have limited impact on overall AAA death rates if incidence is moving to older
      ages. Up-to-date population-based studies of age-specific incidence, risk
      factors, and outcome of acute AAA are needed to inform screening policy. METHODS
      AND RESULTS: In a prospective, population-based study (Oxfordshire, UK, 2002
      2014), the incidence and outcome of acute AAA events were determined. Based on
      population projections and current incidence trends, the impact of screening
      strategies in the UK was estimated. Over the 12-year period, 103 incident acute
      AAA events occurred in the study population of 92 728. Incidence/100 000/year was
      55 in men ages 65 to 74 years, but increased to 112 at 75 to 85 and 298 at >=85,
      with 66.0% of all events occurring at age >=75 years. Incidence at ages 65 to 74
      was highest in male smokers (274), with 96.4% of events in men <75 years
      occurring in ever-smokers. Extrapolating rates to the UK population, using trial
      evidence of screening efficacy, the current UK screening program would prevent
      5.6% of aneurysm-related deaths (315 200 scans/year: 1426/death prevented,
      121/year-of-life saved). Screening only male smokers age 65 and then all men at
      age 75 would prevent 21.1% of deaths (247 900 scans/year; 297/death prevented,
      34/year-of-life saved). By 2030, 91.0% of deaths will occur at age >=75, 61.6% at
      >=85, and 28.6% in women. CONCLUSIONS: Given that two thirds of acute AAA
      occurred at >=75 years of age, screening older age groups should be considered.
      Screening nonsmokers at age 65 is likely to have very little impact on AAA event
      rates.

PMID- 26289349
TI  - Recreational Boating in Ligurian Marine Protected Areas (Italy): A Quantitative
      Evaluation for a Sustainable Management.
AB  - Recreational boating is an important economic activity that can also represent a
      powerful source of interference for biological communities. The monitoring of the
      recreational boating in all Marine Protected Areas (MPAs) within the Liguria
      region was conducted in the 2010 summer season and it allowed to obtain
      information not provided by any official institution. The collaboration of
      geographically different MPAs in Liguria has led to the implementation of a
      monitoring framework of recreational boating, and this has made it possible to
      develop uniform management strategies for all the Ligurian marine parks. This
      study identifies the optimal number of boats for each MPAs, the number of boats
      that can anchor in the various parks without creating any impact on the
      biocenosis of merit, providing a first characterization of recreational boating
      in Liguria during the high touristic season and providing management
      recommendation to each MPAs. Generally, the Ligurian MPAs do not present critical
      situations, the number of boats in each MPA being below the optimal number, with
      the exception of Portofino MPA, where in the 12.5 % of monitored days more than
      220 boats were counted and the mean density for weekend is 1.19 no boats/ha (4
      times higher than weekday). The results confirm the dependence of the boats
      peaking from the holidays and the months of the summer, but also it highlights
      other factors that can contribute in the choice of the boaters. 

PMID- 26289350
TI  - Landowner Satisfaction with the Wetland Reserve Program in Texas: A Mixed-Methods
      Analysis.
AB  - Using mail survey data and telephone interviews, we report on landowner
      satisfaction with permanent easements held by the Natural Resources Conservation
      Service (NRCS) throughout Texas. This study found that landowners were
      dissatisfied with the NRCS Wetland Reserve Program (WRP), conflicting with
      results of previous studies. The objective of this study was to explore specific
      reasons for frustration expressed by landowners with the program. We found three
      predominant themes underpinning program dissatisfaction: (1) upfront restoration
      failures, (2) overly restrictive easement constraints, and (3) bureaucratic
      hurdles limiting landowners' ability to conduct adaptive management on their
      easement property. The implications of this study suggest that attitudes of
      landowners participating in the WRP may limit the long-term effectiveness of this
      program. Suggestions for improving the program include implementing timely,
      ecologically sound restoration procedures and streamlining and simplifying the
      approval process for management activity requests. In addition, the NRCS should
      consider revising WRP restriction guidelines in order to provide more balance
      between protection goals and landowner autonomy. 

PMID- 26289351
TI  - Detecting and Attributing the Effects of Climate Change on the Distributions of
      Snake Species Over the Past 50 Years.
AB  - It is unclear whether the distributions of snakes have changed in association
      with climate change over the past years. We detected the distribution changes of
      snakes over the past 50 years and determined whether the changes could be
      attributed to recent climate change in China. Long-term records of the
      distribution of nine snake species in China, grey relationship analysis, fuzzy
      sets classification techniques, the consistency index, and attributed methods
      were used. Over the past 50 years, the distributions of snake species have
      changed in multiple directions, primarily shifting northwards, and most of the
      changes were related to the thermal index. Driven by climatic factors over the
      past 50 years, the distribution boundary and distribution centers of some species
      changed with the fluctuations. The observed and predicted changes in distribution
      were highly consistent for some snake species. The changes in the northern limits
      of distributions of nearly half of the species, as well as the southern and
      eastern limits, and the distribution centers of some snake species can be
      attributed to climate change.

PMID- 26289354
TI  - Clozapine use for refractory impulse control disorders in Parkinson's disease: a
      case report.

PMID- 26289352
TI  - The FOCUS, AFFINITY and EFFECTS trials studying the effect(s) of fluoxetine in
      patients with a recent stroke: a study protocol for three multicentre randomised
      controlled trials.
AB  - BACKGROUND: Several small trials have suggested that fluoxetine improves
      neurological recovery from stroke. FOCUS, AFFINITY and EFFECTS are a family of
      investigator-led, multicentre, parallel group, randomised, placebo-controlled
      trials that aim to determine whether routine administration of fluoxetine (20 mg
      daily) for 6 months after acute stroke improves patients' functional outcome.
      METHODS/DESIGN: The three trial investigator teams have collaboratively developed
      a core protocol. Minor variations have been tailored to the national setting in
      the UK (FOCUS), Australia and New Zealand (AFFINITY) and Sweden (EFFECTS). Each
      trial is run and funded independently and will report its own results. A
      prospectively planned individual patient data meta-analysis of all three trials
      will subsequently provide the most precise estimate of the overall effect of
      fluoxetine after stroke and establish whether any effects differ between trials
      and subgroups of patients. The trials include patients >=18 years old with a
      clinical diagnosis of stroke, persisting focal neurological deficits at
      randomisation between 2 and 15 days after stroke onset. Patients are randomised
      centrally via web-based randomisation systems using a common minimisation
      algorithm. Patients are allocated fluoxetine 20 mg once daily or matching placebo
      capsules for 6 months. Our primary outcome measure is the modified Rankin scale
      (mRS) at 6 months. Secondary outcomes include the Stroke Impact Scale, EuroQol
      (EQ5D-5 L), the vitality subscale of the Short-Form 36, diagnosis of depression,
      adherence to medication, adverse events and resource use. Outcomes are collected
      at 6 and 12 months. The methods of collecting these data are tailored to the
      national setting. If FOCUS, AFFINITY and EFFECTS combined enrol 6000 participants
      as planned, they would have 90 % power (alpha 5 %) to detect a common odds ratio
      of 1.16, equivalent to a 3.7 % absolute difference in percentage with mRS 0-2
      (44.0 % to 47.7 %). This is based on an ordinal analysis of mRS adjusted for
      baseline variables included in the minimisation algorithm. DISCUSSION: If
      fluoxetine is safe and effective in promoting functional recovery, it could be
      rapidly, widely and affordably implemented in routine clinical practice and
      reduce the burden of disability due to stroke. TRIAL REGISTRATION:  FOCUS:
      ISRCTN83290762 (23/05/2012), AFFINITY: ACTRN12611000774921 (22/07/2011). EFFECTS:
      ISRCTN13020412 (19/12/2014).

PMID- 26289355
TI  - Effects of single dose mixed amphetamine salts--extended release on processing
      speed in multiple sclerosis: a double blind placebo controlled study.
AB  - RATIONALE: Multiple sclerosis (MS) commonly affects cognitive function, most
      frequently presenting as impaired processing speed (PS). There are currently no
      approved treatments for PS in this population, but previous studies suggest
      amphetamines may be beneficial. OBJECTIVE: The objective of this study is to
      determine if mixed amphetamine salts, extended release (MAS-XR) has the potential
      to improve impaired PS in MS patients in a randomized controlled pre- and post
      dose testing study. METHODS: Fifty-two MS patients demonstrating PS impairment on
      either the Symbol Digit Modalities Test (SDMT) or Paced Auditory Serial Addition
      Test (PASAT) were randomized to a single dose of 5 mg MAS-XR (n = 18), 10 mg MAS
      XR (n = 20), or placebo (n = 14). Subjects were evaluated a second time, after
      taking the blinded medication. ANOVA was used to compare the change on the SDMT
      and PASAT in each of the treatment groups compared to the placebo. Cohen's d was
      used to calculate effect size. RESULTS: At baseline, the mean SDMT score was 43.3
      +/- 7.2 and the mean PASAT was 34.8 +/- 13.4, with 47 (90.4 %) and 25 (48.1 %)
      categorized as impaired on the SDMT and PASAT, respectively. The change in SDMT
      scores from baseline to post-treatment demonstrated significant improvement for
      the MAS-XR 10-mg dose compared to placebo, increasing by 5.2 +/- 4.5 vs. 0.6 +/-
      4.4 points (p = 0.043), with a medium effect size of 0.47. Change on the PASAT
      was not significantly different in either treatment group. CONCLUSIONS: This
      study supports MAS-XR 10 mg as a potential treatment for MS patients with
      demonstrated PS impairment, warranting a larger longitudinal study.

PMID- 26289356
TI  - Comparison of Eylea(r) with Lucentis(r) as first-line therapy in patients with
      treatment-naive neovascular age-related macular degeneration in real-life
      clinical practice: retrospective case-series analysis.
AB  - BACKGROUND: To identify differences between Ranibizumab and Aflibercept in
      treatment-naive patients with neovascular age-related macular degeneration
      (nvAMD) in a real-life clinical setting. METHODS: We compared two groups of
      patients with a fairly similar prognosis either receiving Aflibercept or
      Ranibizumab within a pro re nata regimen for 1 year. Changes in visual acuity
      (letters) and central foveal thickness (CFT) and frequency of injections after
      completing the loading phase were evaluated using two separate multivariate mixed
      linear models. RESULTS: When correcting for baseline differences between the
      Aflibercept (11 eyes) and Ranibizumab (16 eyes) group, there was neither
      divergence in visual acuity (-0.97 letters (95 % CI. -6.06-4.12); p = 0.709), nor
      a significant difference in the reduction of CFT (-25.16 MUm, 95 % CI; (-78.01
      27.68); p = 0.351) between the two groups 1 year after treatment initiation.
      Also, the number of injection did not differ (0.04 (95 % CI; -0.16-0.09); p =
      0.565). CONCLUSION: In contrast to health claims, treatment-naive nvAMD,
      Ranibizumab and Aflibercept were equivalent in terms of functional and
      morphologic outcomes and number of injections when studied in real-life clinical
      practice.

PMID- 26289357
TI  - Role models in a preventive program for hand eczema among healthcare workers: a
      qualitative exploration of their main tasks and associated barriers and
      facilitators.
AB  - BACKGROUND: Role models often play a role when implementing guidelines in
      healthcare. However, little is known about how role models perform their
      respective roles, or about which factors may hamper or enhance their functioning.
      The aim of the present study was therefore to investigate how role models perform
      there role as a part of a multifaceted implementation strategy on the prevention
      of hand eczema, and to identify barriers and facilitators for the performing of
      their role. METHODS: The role models were selected to become a role model and
      received a role model training. All role models worked at a hospital. In total,
      19 role models, were interviewed. A topic list was used focussing on how the role
      models performed their role and what they experienced to be facilitators and
      barriers for their role. After coding the interviews, the codes were divided into
      themes. RESULTS: This study shows that the main tasks perceived by the role
      models were to raise awareness, to transfer information, to interact with
      colleagues about hand eczema, to provide material, and to perform coordinating
      tasks. Barriers and facilitators were whether the role suited the participant,
      affinity with the topic, and risk perception. CONCLUSIONS: Most role models
      performed only the tasks they learned during their training. They mentioned a
      wide range of barriers and facilitators for the performing of their role. To
      enhance the functioning of the role models, a suggestion would be to select role
      models by taking into account prior coaching experience. TRIAL REGISTRATION: 
      TRIAL REGISTRATION NUMBER: NTR2812.

PMID- 26289353
TI  - Treatment-resistant depression: are animal models of depression fit for purpose?
AB  - BACKGROUND: Resistance to antidepressant drug treatment remains a major health
      problem. Animal models of depression are efficient in detecting effective
      treatments but have done little to increase the reach of antidepressant drugs.
      This may be because most animal models of depression target the reversal of
      stress-induced behavioural change, whereas treatment-resistant depression is
      typically associated with risk factors that predispose to the precipitation of
      depressive episodes by relatively low levels of stress. Therefore, the search for
      treatments for resistant depression may require models that incorporate
      predisposing factors leading to heightened stress responsiveness. METHOD: Using a
      diathesis-stress framework, we review developmental, genetic and genomic models
      against four criteria: (i) increased sensitivity to stress precipitation of a
      depressive behavioural phenotype, (ii) resistance to chronic treatment with
      conventional antidepressants, (iii) a good response to novel modes of
      antidepressant treatment (e.g. ketamine; deep brain stimulation) that are
      reported to be effective in treatment-resistant depression and (iv) a parallel to
      a known clinical risk factor. RESULTS: We identify 18 models that may have some
      potential. All require further validation. Currently, the most promising are the
      Wistar-Kyoto (WKY) and congenital learned helplessness (cLH) rat strains, the
      high anxiety behaviour (HAB) mouse strain and the CB1 receptor knockout and OCT2
      null mutant mouse strains. CONCLUSION: Further development is needed to validate
      models of antidepressant resistance that are fit for purpose. The criteria used
      in this review may provide a helpful framework to guide research in this area.

PMID- 26289358
TI  - Sparsity-based Ankylography for Recovering 3D molecular structures from single
      shot 2D scattered light intensity.
AB  - Deciphering the three-dimensional (3D) structure of complex molecules is of major
      importance, typically accomplished with X-ray crystallography. Unfortunately,
      many important molecules cannot be crystallized, hence their 3D structure is
      unknown. Ankylography presents an alternative, relying on scattering an
      ultrashort X-ray pulse off a single molecule before it disintegrates, measuring
      the far-field intensity on a two-dimensional surface, followed by computation.
      However, significant information is absent due to lower dimensionality of the
      measurements and the inability to measure the phase. Recent Ankylography
      experiments attracted much interest, but it was counter-argued that Ankylography
      is valid only for objects containing a small number of volume pixels. Here, we
      propose a sparsity-based approach to reconstruct the 3D structure of molecules.
      Sparsity is natural for Ankylography, because molecules can be represented
      compactly in stoichiometric basis. Utilizing sparsity, we surpass current limits
      on recoverable information by orders of magnitude, paving the way for deciphering
      the 3D structure of macromolecules. 

PMID- 26289359
TI  - If three of my brothers have ankylosing spondylitis, why does the doctor say it
      is not necessarily hereditary? The meaning of risk in multiplex case families
      with ankylosing spondylitis.
AB  - OBJECTIVE: To investigate how patients with ankylosing spondylitis and their
      relatives in multiplex case families understand concepts of familial aggregation,
      heredity and risk perceptions, and its impact on decision-making. METHODS: This
      is a multimethod clinical investigation using field research style in 34
      individuals from 10 families with >=2 members with ankylosing spondylitis
      covering a wide spectrum of disease severity, educational level, and economical
      status. The narratives of patients and their relatives were obtained using
      clinical information, unstructured observation, and personal interviews, which
      were then transcribed verbatim, coded, and analyzed by three investigators. The
      interpretation of the textual data was based on two analysis styles,
      immersion/crystallization and interpretative grounded theory. RESULTS: We
      identified four broad interrelated interpretive units in patient and relatives
      narratives: (1) familial interpretation of the disease, (2) genetic risk, (3)
      decision-making based on risk, and (4) patient-family/physician discourse
      contradiction on the meaning of heredity. CONCLUSIONS: Patient's and their
      relatives interpretation of familial aggregation, HLAB27, heredity, and risk
      perception in relation with ankylosing spondylitis involves four broad
      interpretive units spanning from clinical symptoms to heredity and decisions made
      accordingly. Their thoughts and consequent decisions are often in contradiction
      with the medical knowledge on the role of genetic factors in ankylosing
      spondylitis.

PMID- 26289360
TI  - Adverse events experienced by participants in a back pain walking intervention: A
      descriptive study.
AB  - OBJECTIVE: To understand the range and potential severity of adverse events
      reported by patients with back pain who were participating in a walking
      intervention. METHODS: Data were obtained from participants in a randomized trial
      of a pedometer-based Internet-mediated intervention to promote walking and reduce
      back pain-related disability (n = 229 participants, 118 usual care, and 111
      intervention). Participants reported adverse events throughout the 12-month study
      period. All reported events were reviewed and classified by system, severity, and
      study relatedness. RESULTS: A total of 600 adverse events were reported, 250 by
      those in usual care and nearly 350 by those in the intervention. After worsening
      back pain (27%), musculoskeletal events were the most commonly reported events
      (19%), followed by cardiovascular events (14%), infection (11%), and medical
      procedures (9%). There were three times as many musculoskeletal events in the
      intervention compared to the usual care group. Cardiovascular events, which were
      generally not serious and not walking related, were far less common than
      musculoskeletal injuries. CONCLUSIONS: Individuals with chronic back pain can
      safely engage in a pedometer-based, unsupervised walking program. However,
      patients may benefit from focused counseling about musculoskeletal risks with
      specific attention to injury prevention measures such as gradually incrementing
      activity levels.

PMID- 26289361
TI  - Informational needs of liver transplant recipients during a two-year
      posttransplant period.
AB  - OBJECTIVES: To describe the informational needs of liver transplant (LTx)
      recipients, examine potential differences in informational needs by
      sociodemographic and clinical variables, and examine informational needs at
      various time points posttransplant. METHODS: A descriptive, cross-sectional
      design was used. Informational needs were assessed by the Informational Needs
      Questionnaire-liver, a new questionnaire developed to include LTx recipients'
      perspectives. To examine informational needs at different posttransplant time
      points, participants were classified into four groups (0-1, 2-4, 5-9, and 10-24
      months). RESULTS: Participants (159) who were married, single, had higher
      education, or higher monthly incomes had significantly greater informational
      needs. Informational needs regarding disease and physical and emotional
      management remained high after transplant. Four subscales (medication, wound
      management, diet, and daily and social activities) indicated informational needs
      were different across time. Participants 2-4 months posttransplant had higher
      informational needs regarding wound management and daily and social activities.
      Participants 5-9 months posttransplant had the highest informational needs
      regarding medication and diet. DISCUSSION: Findings indicate informational needs
      vary among LTx recipients at different posttransplant time points. Marital
      status, education, and monthly income can influence informational needs.
      CONCLUSION: Healthcare providers should tailor information given to LTx
      recipients based on informational needs. Longitudinal studies are needed to
      confirm changing patterns of informational needs.

PMID- 26289362
TI  - The effects of corticosteroids on COPD lung macrophages: a pooled analysis.
AB  - BACKGROUND: There is large variation in the therapeutic response to inhaled
      corticosteroids (ICS) in COPD patients. We present a pooled analysis of our
      previous studies investigating the effects of corticosteroids on lung
      macrophages, in order to robustly determine whether corticosteroid sensitivity in
      COPD cells is reduced compared to controls, and also to evaluate the degree of
      between individual variation in drug response. METHODS: Data from 20 never
      smokers (NS), 27 smokers (S) and 45 COPD patients was used. Lung macropahges had
      been stimulated with lipopolysaccharide (LPS), with or without the corticosteroid
      dexamethasone, and tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and
      chemokine C-X-C motif ligand (CXCL) 8 production was measured. RESULTS: There was
      no difference in the anti-inflammatory effects of corticosteroids when comparing
      group mean data of COPD patients versus controls. The inhibition of TNF-alpha and
      IL-6 was greater than CXCL8. The effects of corticosteroids varied considerably
      between subjects, particularly at lower corticosteroid concentrations.
      CONCLUSIONS: We confirm that overall corticosteroid sensitivity in COPD lung
      macrophages is not reduced compared to controls. The varied effect of
      corticosteroids between subjects suggests that some individuals have an
      inherently poor corticosteroid response. The limited suppression of lung
      macrophage derived CXCL8 may promote neutrophilic inflammation in COPD.

PMID- 26289363
TI  - LncRNAs: emerging biomarkers in gastric cancer.
AB  - Long noncoding RNAs (lncRNAs) recently have been recognized as having a critical
      role in cancer development and progression. Gastric cancer remains a major
      clinical challenge worldwide owing to poor prognosis and limited treatment
      options. Accumulating studies have demonstrated that lncRNAs may play an active
      role in tumorigenesis, metastasis, prognosis and drug resistance of gastric
      cancer. Here, we collect recent knowledge to show differential expression of
      lncRNA in gastric cancer and their underlying mechanism of activities in gastric
      cancer involved in epigenetic, transcription and post-transcriptional processing.
      This review focuses on the regulation and function of gastric cancer-related
      lncRNAs and provides an overview of current effects to exploit them to be
      potential biomarkers and therapeutic targets for gastric cancer. 

PMID- 26289364
TI  - Vaccination in patients with primary immune deficiency, secondary immune
      deficiency and autoimmunity with immune regulatory abnormalities.
AB  - Vaccination has been an important healthcare measure in preventing infectious
      diseases. The response to vaccination is reduced in immunocompromised patients,
      primary immune deficiency (PID) and secondary immune deficiency (SID), but
      vaccination studies still demonstrated a protective effect resulting in reducing
      complications, hospitalization, treatment costs and even mortality. The primary
      physician and the specialist directing patient care are responsible for
      vaccination. Live vaccines are contraindicated in patients with severe immune
      impairment, killed vaccines are highly recommended in PID and SID. Criteria have
      been defined to distinguish high- or low-level immune impairment in the different
      disease entities among PID and SID patients. For patients who do not respond to
      diagnostic vaccination as characterized by antibody failure immunoglobulin
      replacement is the mainstay of therapy. 

PMID- 26289365
TI  - Heated birthing pools as a source of Legionnaires' disease.
AB  - In June 2014 Public Health England confirmed a case of Legionnaires' disease (LD)
      in a neonate following birth at home in a hired birthing pool incorporating a
      heater and a recirculation pump which had been filled in advance of labour. The
      case triggered a public health investigation and a microbiological survey of an
      additional ten heated birthing pools hired or recently hired to the general
      public across England. The birthing pool used by the parent of the confirmed case
      was identified as the source of the neonate's infection following detection of
      Legionella pneumophila ST48 in both patient and environmental samples. Legionella
      species were detected by quantitative polymerase chain reaction but not culture
      in a further three pools together with other opportunistic pathogens identified
      by culture and matrix-assisted laser desorption ionization-time of flight (MALDI
      ToF) mass spectrometry. A Patient Safety Alert from NHS England and Public Health
      England was issued stating that heated birthing pools filled in advance of labour
      should not be used for home births. This recommendation remains in place. This
      investigation in conjunction with other recent reports has highlighted a lack of
      awareness regarding the microbiological safety of heated birthing pools and their
      potential to be a source of LD and other opportunistic infections. Furthermore,
      the investigation raised important considerations with regards to microbiological
      sampling and testing in such incidents. Public health authorities and clinicians
      should consider LD in the differential diagnosis of severe respiratory infection
      in neonates within 14 days of a water birth. 

PMID- 26289368
TI  - Utility of the Community Integration Questionnaire in a sample of adults with
      neurological and neuropsychiatric disorders receiving prevocational training.
AB  - PURPOSE: To investigate utility of the Community Integration Questionnaire (CIQ)
      in a mixed sample of adults with neurological and neuropsychiatric disorders.
      METHOD: Cross-sectional, interview-based study. Participants were community
      dwelling adults with disabilities resulting from neurological and
      neuropsychiatric disorders (N = 54), who participated in a pre-vocational
      readiness and social skills training program. Psychometric properties of the
      Community Integration Questionnaire (CIQ) were assessed and validated against
      Mayo-Portland Adaptability Inventory (MPAI) and The Problem Checklist from the
      New York University Head Injury Family Interview (PCL). RESULTS: Based on the
      revised scoring procedures, psychometric properties of the CIQ Home Competency
      scale were excellent, followed by the Total score and Social Integration scale.
      Productive Activity scale had low content validity and a weak association with
      the total score. Convergent and discriminant validity of the CIQ were
      demonstrated by correlation patterns with MPAI scales in the expected direction.
      Significant relationship was found with PCL Physical/Dependency scale.
      Significant associations were found with sex, living status, and record of
      subsequent employment. CONCLUSIONS: The results provide support for the use of
      the CIQ as a measure of participation in individuals with neurological and
      neuropsychiatric diagnoses and resulting disabilities. IMPLICATIONS FOR
      REHABILITATION: An important goal of rehabilitation and training programs for
      individuals with dysfunction of the central nervous system is to promote their
      participation in social, vocational, and domestic activities. The Community
      Integration Questionnaire (CIQ) is a brief and efficient instrument for measuring
      these participation domains. This study demonstrated good psychometric properties
      and high utility of the CIQ in a sample of 54 individuals participating in a
      prevocational training program.

PMID- 26289369
TI  - Children's contact with people with disabilities and their attitudes towards
      disability: a cross-sectional study.
AB  - PURPOSE: To explore the association between children's self-reported contact with
      people with disabilities and attitudes towards them, as well the potential
      mediating influence of anxiety about interacting with people with disabilities
      and empathy for them. METHOD: 1881 children, aged 7-16 years, from 20 schools in
      South West England completed a survey assessing their contact with people with
      disabilities and their attitudes towards them. Anxiety about interacting with
      people with disabilities and empathy towards them were examined as potential
      mediators. Gender, school year, perceived similarity between people with and
      without disabilities, proportion of children with additional needs at the school
      and socioeconomic status (SES) were assessed as moderators. A random effects
      ("multilevel") regression model was used to test the contact-attitude association
      and moderation, and path analysis was used to test for mediation. RESULTS:
      Participants with more self-reported contact reported more positive attitudes
      towards disability (p < 0.001). Less anticipated anxiety and greater empathy
      together mediated around a third of this association. Only school year moderated
      the contact-attitude association (affective attitudes), with stronger contact
      attitude associations in primary school children than secondary school children.
      CONCLUSIONS: Self-reported contact was observed to be associated with more
      positive attitudes towards disability, which was partially mediated by empathy
      and anxiety. Providing opportunities for contact with people with disabilities
      that reduces anxiety and increases empathy may improve attitudes to disability
      and merits evaluation in interventions. IMPLICATIONS FOR REHABILITATION: Children
      who reported greater levels of contact with people with disabilities had more
      positive attitudes towards disability. Anxiety about interacting with people with
      disabilities and empathy towards them partially mediated the contact-attitude
      associations. Providing opportunities for contact with people with disabilities,
      reducing anxiety and increasing empathy may improve children's attitudes to
      disability.

PMID- 26289371
TI  - The effect of rater training on scoring performance and scale-specific expertise
      amongst occupational therapists participating in a multicentre study: a single
      group pre-post-test study.
AB  - PURPOSE: In order to enhance the quality of the data collected in a multicentre
      validation study of a revised Danish version of the McGill Ingestive Skills
      Assessment (MISA), the authors developed a rater training programme. The purpose
      of the present study was to evaluate the effect of the training on scoring
      performance and scale-specific expertise amongst raters. METHOD: During 2 days of
      rater training, 81 occupational therapists (OTs) were qualified to observe and
      score dysphagic clients' mealtime performance according to the criteria of 36
      MISA-items. The training effects were evaluated pre- to post-training using
      percentage exact agreement (PA) of scored MISA items of a case-vignette and a
      Likert scale self-report of scale-specific expertise. RESULTS: PA increased
      significantly from pre- to post-training (Z = -4.404, p < 0.001), although items
      for which the case-vignette reflected deficient mealtime performance appeared
      most difficult to score. The OTs scale-specific expertise improved significantly
      (knowledge: Z = -7.857, p < 0.001 and confidence: Z = -7.838, p < 0.001).
      CONCLUSION: Rater training improved OTs scoring performance when using the Danish
      MISA as well as their perceived scale-specific expertise. Future rater training
      should emphasis the items identified as those most difficult to score.
      Additionally, further studies addressing different training approaches and
      durations are warranted. IMPLICATIONS FOR REHABILITATION: When occupational
      therapists (OTs) use the McGill Ingestive Skills Assessment (MISA) they observe,
      interpret and record occupational performance of dysphagic clients participating
      in a meal. This is a highly complex task, which might introduce unwanted
      variability in measurement scores. A 2-day rater training programme was developed
      and this builds on the findings of several studies. These suggest that
      combinations of different training methods tend to yield the most effective
      results. Participation in the newly developed training programme on how to
      administer the MISA significantly reduces unwanted variability in measurement
      scores and improves OTs' competency. The training programme could be used in
      undergraduate and postgraduate dysphagia education initiatives to help OTs
      understanding of the content and the scoring criteria for each aspect of
      occupational performance during a meal, thus developing observation skills as
      well as recognizing and avoiding the most common errors in measurement scores.

PMID- 26289372
TI  - Psychosocial difficulties from the perspective of persons with neuropsychiatric
      disorders.
AB  - PURPOSE: The objective of this study is to determine whether persons with
      neuropsychiatric disorders experience a common set of psychosocial difficulties
      using qualitative data from focus groups and individual interviews. METHOD: The
      study was performed in five European countries (Finland, Italy, Germany, Poland
      and Spain) using the focus groups and individual interviews with persons with
      nine neuropsychiatric disorders (dementia, depression, epilepsy, migraine,
      multiple sclerosis, Parkinson's disease, schizophrenia, stroke and substance
      dependence). Digitally recorded sessions were analysed using a step-by-step
      qualitative and quantitative methodology resulting in the compilation of a common
      set of psychosocial difficulties using the International Classification of
      Functioning, Disability and Health (ICF) as a framework. RESULTS: Sixty-seven
      persons participated in the study. Most persons with neuropsychiatric disorders
      experience difficulties in emotional functions, sleeping, carrying out daily
      routine, working and interpersonal relationships in common. Sixteen out of 33
      psychosocial difficulties made up the common set. This set includes mental
      functions, pain and issues addressing activities and participation and provides
      first evidence for the hypothesis of horizontal epidemiology of psychosocial
      difficulties in neuropsychiatric disorders. CONCLUSIONS: This study provides
      information about psychosocial difficulties that should be covered in the
      treatment and rehabilitation of persons with neuropsychiatric disorders
      regardless of clinical diagnoses. IMPLICATIONS FOR REHABILITATION: Emotional
      problems, work and sleep problems should be addressed in all the treatments of
      neuropsychiatric disorders regardless of their specific diagnosis, etiology and
      severity. Personality issues should be targeted in the treatment for neurological
      disorders, whereas communication skill training may also be useful for mental
      disorders. The effects of medication and social environment on patient's daily
      life should be considered in all the neuropsychiatric conditions.

PMID- 26289373
TI  - Factors associated with changes in mobility and living arrangements in a
      comprehensive geriatric outpatient assessment after hip fracture.
AB  - PURPOSE: To examine factors associated with changes in mobility and living
      arrangements in a comprehensive geriatric outpatient assessment after hip
      fracture. METHOD: Population-based prospective data on 887 consecutive hip
      fracture patients aged 65 years and older. The domains of the geriatric
      assessment were the independent and changes in mobility level and living
      arrangements 4 months postoperatively the outcome variables. RESULTS: Of the
      survivors, 499 (73%) attended the assessment. The mobility level had declined in
      39% of the attendees and 38% of them had moved to more supported living
      arrangements 4 months after the hip fracture. In the age-adjusted univariate
      logistic regression analyses, almost all the domains of the comprehensive
      geriatric assessment were significantly associated with both outcomes. In the
      forward stepwise multivariate analysis, disability in activities of daily living,
      poor performance in Timed Up and Go and comorbidity as measured by the American
      Society of Anesthesiologists scores remained significantly associated with the
      outcomes. CONCLUSIONS: While comorbidity and disability in activities of daily
      living and mobility are the major indicators of poor outcomes of mobility and
      living arrangements after hip fracture, all the domains in the comprehensive
      geriatric assessment deserve attention during hip fracture care and
      rehabilitation. IMPLICATIONS FOR REHABILITATION: In almost half of the patients
      the mobility level and living arrangements had deteriorated 4 months after the
      hip fracture, suggesting an urgent need for more effective postoperative
      rehabilitation. Almost all the domains of the comprehensive geriatric assessment
      were associated with poor outcomes and require equal attention during the acute
      and postacute phases of hip fracture care and in the course of rehabilitation. A
      geriatric outpatient assessment a few months after the hip fracture provides a
      check-point for the outcomes and an opportunity to target interventions at
      different domains of the comprehensive assessment.

PMID- 26289374
TI  - Antibiotic resistance in patients with primary immunodeficiency disorders versus
      immunocompetent patients.
AB  - OBJECTIVES: We aimed to investigate the antimicrobial susceptibility among
      bacterial isolates of patients with primary immunodeficiency disorders (PID) in
      comparison with immunocompetent patients. METHODS: Patients' antibiotic
      sensitivity profiles were extracted from their medical records. In order to
      compare the antibiotic sensitivity profiles of PID patients with immunocompetent
      patients, the results of antibiograms of patients who did not have a known or
      suspected immunodeficiency and were hospitalized during the same period were
      obtained and used as control subjects. RESULTS: A total number of 257 isolates
      were obtained from 86 PID patients. Antimicrobial susceptibilities of several
      organisms isolated from PID patients were significantly lower compared to that of
      immunocompetent patients. CONCLUSION: Antibiotic resistance seems to be higher
      among PID patients compared to immunocompetent patients. This indicates a need
      for further investigations for the possible factors responsible for antibiotic
      resistance in PID patients.

PMID- 26289375
TI  - Novel imaging approaches in adult asthma and their clinical potential.
AB  - Currently, imaging in asthma is confined to chest radiography and CT. The
      emergence of new imaging techniques and tremendous improvement of existing
      imaging methods, primarily due to technological advancement, has completely
      changed its research and clinical prospects. In research, imaging in asthma is
      now being employed to provide quantitative assessment of morphology, function and
      pathogenic processes at the molecular level. The unique ability of imaging for
      non-invasive, repeated, quantitative, and in vivo assessment of structure and
      function in asthma could lead to identification of 'imaging biomarkers' with
      potential as outcome measures in future clinical trials. Emerging imaging
      techniques and their utility in the research and clinical setting is discussed in
      this review. 

PMID- 26289377
TI  - Different brands of intravenous immunoglobulin for primary immunodeficiencies:
      how to choose the best option for the patient?
AB  - Immunoglobulin (IG) replacement therapy has served as lifesaving treatment in
      primary immunodeficiency diseases (PID) for more than six decades. Approximately
      70% of patients with PID require IG replacement to maintain their health during
      the course of disease. It is estimated that about one-third of IG products is
      used for replacement therapy in these patients. On the other hand, the
      introduction of newer IG preparations is continuing to improve and extend the
      quality of life in PID patients. Because of the options available including
      concentrations, formulations, osmolality, product stabilizers, sodium
      concentration, anti-infective activity, IgA content and pH, it is important to
      match the PID patient's complications with potential side effects associated with
      the composition of a particular IG product. The purpose of this review is to
      present the clinical differences of intravenous IG among the various preparations
      regarding PID patients. 

PMID- 26289376
TI  - Exploring cell-based tolerance strategies for hand and face transplantation.
AB  - Broader clinical application of reconstructive hand and face transplantation is
      hindered by the need for lifelong immunosuppression for allograft maintenance. In
      this review, we summarize various cell-based approaches to tolerance induction
      currently under investigation in both clinical and pre-clinical models to
      alleviate the need for chronic immunosuppression. These include strategies to
      induce mixed hematopoietic chimerism, therapy with T and B regulatory cells,
      regulatory macrophages, tolerogenic dendritic cells, and mesenchymal stem cells.
      The vascularized, intragraft bone components inherent to reconstructive
      transplants serve as a continuous source of donor-derived hematopoietic cells,
      and make hand and face transplants uniquely well suited for cell-based approaches
      to tolerance that may ultimately tilt the risk-benefit balance for these life
      changing, but not life-saving, procedures. 

PMID- 26289378
TI  - PredRet: prediction of retention time by direct mapping between multiple
      chromatographic systems.
AB  - Demands in research investigating small molecules by applying untargeted
      approaches have been a key motivator for the development of repositories for mass
      spectrometry spectra and automated tools to aid compound identification.
      Comparatively little attention has been afforded to using retention times (RTs)
      to distinguish compounds and for liquid chromatography there are currently no
      coordinated efforts to share and exploit RT information. We therefore present
      PredRet; the first tool that makes community sharing of RT information possible
      across laboratories and chromatographic systems (CSs). At http://predret.org , a
      database of RTs from different CSs is available and users can upload their own
      experimental RTs and download predicted RTs for compounds which they have not
      experimentally determined in their own experiments. For each possible pair of CSs
      in the database, the RTs are used to construct a projection model between the RTs
      in the two CSs. The number of compounds for which RTs can be predicted and the
      accuracy of the predictions are dependent upon the compound coverage overlap
      between the CSs used for construction of projection models. At the moment, it is
      possible to predict up to 400 RTs with a median error between 0.01 and 0.28 min
      depending on the CS and the median width of the prediction interval ranging from
      0.08 to 1.86 min. By comparing experimental and predicted RTs, the user can thus
      prioritize which isomers to target for further characterization and potentially
      exclude some structures completely. As the database grows, the number and
      accuracy of predictions will increase. 

PMID- 26289380
TI  - Born-Oppenheimer and Renner-Teller coupled-channel quantum reaction dynamics of
      O((3)P) + H2(+)(X(2)Sigmag(+)) collisions.
AB  - We present Born-Oppenheimer (BO) and Renner-Teller (RT) time dependent quantum
      dynamics studies of the reactions O((3)P) + H2(+)(X(2)Sigmag(+)) ->
      OH(+)(X(3)Sigma(-)) + H((2)S) and OH(X(2)Pi) + H(+). We consider the OH2(+)
      X[combining tilde](2)A'' and A(2)A' electronic states that correlate with a
      linear (2)Pi species. The electronic angular momenta operators L[combining
      circumflex] and L[combining circumflex](2) are considered in nonadiabatic coupled
      channel calculations, where the associated RT effects are due to diagonal V(RT)
      potentials that add up to the PESs and to off-diagonal C(RT) couplings between
      the potential energy surfaces (PESs). Initial-state-resolved reaction
      probabilities PI, integral cross sections sigmaI, and rate constants kI are
      obtained using recent ab initio PESs and couplings and the real wavepacket
      formalism. Because the PESs are strongly attractive, PI have no threshold energy
      and are large, sigmaI decrease with collision energy, and kI depend little on the
      temperature. The X[combining tilde](2)A'' PES is up to three times more reactive
      than the A(2)A' PES and H2(+) rotational effects (j0 = 0, 1) are negligible. The
      diagonal V(RT) potentials are strongly repulsive at the collinearity and nearly
      halve all low-energy observables with respect to the BO ones. The off-diagonal
      C(RT) couplings are important at low partial waves, where they mix the
      X[combining tilde](2)A'' and A(2)A' states up to ~20%. However, V(RT) effects
      predominate over the C(RT) ones that change at most by ~19% the BO values of
      sigmaI and kI. The reaction O((3)P) + H2(+)(X(2)Sigmag(+)) -> OH(+)(X(3)Sigma(-))
      + H((2)S) is probably one of the most reactive atom + diatom collisions because
      its RT rate constant at room temperature is equal to 2.26 * 10(-10) cm(3) s(-1).
      Within the BO approximation, the present results agree rather well with recent
      quasiclassical and centrifugal-sudden data using the same PESs. 

PMID- 26289379
TI  - Impact of Extreme Heat Events on Emergency Department Visits in North Carolina
      (2007-2011).
AB  - Extreme heat is the leading cause of weather-related mortality in the U.S.
      Extreme heat also affects human health through heat stress and can exacerbate
      underlying medical conditions that lead to increased morbidity and mortality. In
      this study, data on emergency department (ED) visits for heat-related illness
      (HRI) and other selected diseases were analyzed during three heat events across
      North Carolina from 2007 to 2011. These heat events were identified based on the
      issuance and verification of heat products from local National Weather Service
      forecast offices (i.e. Heat Advisory, Heat Watch, and Excessive Heat Warning).
      The observed number of ED visits during these events were compared to the
      expected number of ED visits during several control periods to determine excess
      morbidity resulting from extreme heat. All recorded diagnoses were analyzed for
      each ED visit, thereby providing insight into the specific pathophysiological
      mechanisms and underlying health conditions associated with exposure to extreme
      heat. The most common form of HRI was heat exhaustion, while the percentage of
      visits with heat stroke was relatively low (<10%). The elderly (>65 years of age)
      were at greatest risk for HRI during the early summer heat event (8.9 visits per
      100,000), while young and middle age adults (18-44 years of age) were at greatest
      risk during the mid-summer event (6.3 visits per 100,000). Many of these visits
      were likely due to work-related exposure. The most vulnerable demographic during
      the late summer heat event was adolescents (15-17 years of age), which may relate
      to the timing of organized sports. This demographic also exhibited the highest
      visit rate for HRI among all three heat events (10.5 visits per 100,000).
      Significant increases (p < 0.05) in visits with cardiovascular and
      cerebrovascular diseases were noted during the three heat events (3-8%). The
      greatest increases were found in visits with hypotension during the late summer
      event (23%) and sequelae during the early summer event (30%), while decreases
      were noted for visits with hemorrhagic stroke during the middle and late summer
      events (13-24%) and for visits with aneurysm during the early summer event (15%).
      Significant increases were also noted in visits with respiratory diseases (5-7%).
      The greatest increases in this category were found in visits with pneumonia and
      influenza (16%), bronchitis and emphysema (12%), and COPD (14%) during the early
      summer event. Significant increases in visits with nervous system disorders were
      also found during the early summer event (16%), while increases in visits with
      diabetes were noted during the mid-summer event (10%).

PMID- 26289381
TI  - The effect of N-methylation of amino acids (Ac-X-OMe) on solubility and
      conformation: a DFT study.
AB  - N-Methylation has a significant impact on improving the oral bioavailability,
      lipophilicity and aqueous solubility of peptide-based lead drug structures. The
      selected mono-amino acid derivatives Ac-X-OMe, where X = Gly, Val, Leu, Ile, Phe,
      Met, Cys, Ser, Asp and His as well as their corresponding N-methylated analogues
      were studied. The clog P values of all N-methylated peptides are greater than
      those of native compounds. Quantum chemical calculations were performed to
      estimate the aqueous solubility of these lipophilic compounds using density
      functional theory (DFT). To confirm the contribution of dispersion forces on
      quantum chemical data, the long-range corrected (LC) hybrid density functional
      (omegaB97X-D) was also probed for some amino acid derivatives. The omegaB97X
      functional gave similar results. Our results reveal that after mono N-methylation
      of the peptide backbone, DeltaGsolv becomes more negative (more water soluble)
      while polarizability and dipole moment are also increased. Natural atomic charges
      derived by natural bond orbital (NBO) analysis of N, C, and O atoms involved in
      amide functional group become more positive/(less negative) after N-methylation.
      All N-methylated amino acids have higher EHOMO (less negative) in comparison with
      the amino acid analogues, and in all cases N-methylation decreases EHOMO-LUMO.
      The calculated amide cis/trans activation energies (EA) of all the N-methylated
      amino acid derivatives were lower than that of native species. N-methylation of
      these compounds leads to an increase in lipophilicity, aqueous solubility,
      polarization, dipole moment and lowering of the cis/trans amide energy barrier
      (EA). 

PMID- 26289382
TI  - Over-expression of EPS15 is a favorable prognostic factor in breast cancer.
AB  - As a crucial player in terminating growth factor signaling, EPS15 plays important
      roles in many malignancies including breast cancer. To explore the potential
      association of EPS15 with the clinical outcome of breast cancer, we conducted
      gene expression survival analysis using six independent datasets, checked its
      expression quantitative loci and their associated genes, and explored the
      networking of these genes with EPS15. Our results show that over-expression of
      EPS15 is significantly associated with a favorable clinical outcome of breast
      cancer, especially in tumors harbouring a positive estrogen receptor status. 21
      unique SNPs were found to be associated with EPS15 expression. Among the
      neighboring genes of these SNPs, five (MTUS1, DOCK5, MSRA, SLIT3 and SKAP1) are
      genetically connected with EPS15 and its physical partners. These genes including
      EPS15 also show significant concurrent expressions, and four exhibit distinct
      relevance regarding patient survival. High expressions of EPS15 and MSRA show a
      distinct combinatorial favorable survival, suggesting the clinical relevance of
      their co-activation. In summary, over-expression of EPS15 is a potential
      favorable prognostic marker in breast cancer, which can be used clinically alone
      or together with other genes such as MSRA to avail therapeutic decision-making. 

PMID- 26289383
TI  - Competing noncovalent host-guest interactions and H/D exchange: reactions of
      benzyloxycarbonyl-proline glycine dipeptide variants with ND3.
AB  - A combination of density functional theory calculations, hydrogen/deuterium
      exchange (HDX) reactions, ion mobility-mass spectrometry, and isotope labeling
      tandem mass spectrometry was used to study gas-phase "host-guest" type
      interactions of a benzyloxycarbonyl (Z)-capped proline (P) glycine (G) model
      dipeptide (i.e., Z-PG) and its various structural analogues with ND3. It is shown
      that in a solvent-free environment, structural differences between protonated and
      alkali metal ion (Na(+), K(+), or Cs(+))-complexed species of Z-PG affect ND3
      adduct formation. Specifically, [Z-PG + H](+) and [Z-PG-OCH3 + H](+) formed gas
      phase ND3 adducts ([Z-PG (or Z-PG-OCH3) + H + ND3](+)) but no ND3 adducts were
      observed for [Z-PG + alkali metal](+) or [Z-PG + H - CO2](+). Experimentally
      measured and theoretically calculated collision cross sections (CCSs) of
      protonated and alkali metal ion-complexed Z-PG species showed similar trends that
      agreed with the observed structural differences from molecular modeling results.
      Moreover, results from theoretical ND3 affinity calculations were consistent with
      experimental HDX observations, indicating a more stable ND3 adduct for [Z-PG +
      H](+) compared to [Z-PG + alkali metal](+) species. Molecular modeling and
      experimental MS results for [Z-PG + H](+) and [Z-PG + alkali metal](+) suggest
      that optimized cation-pi and hydrogen bonding interactions of carbonyl groups in
      final products are important for ND3 adduct formation. Graphical Abstract ?. 

PMID- 26289384
TI  - Epithelial Dysplasia in Ameloblastic Fibrosarcoma Arising from Recurrent
      Ameloblastic Fibroma in a 26-Year-Old Iranian Man.
AB  - BACKGROUND Ameloblastic fibrosarcoma (AFS) is a rare malignant odontogenic tumor
      with a mesenchymal component, showing sarcomatous features and epithelial nests
      resembling ameloblastic fibroma (AF). CASE REPORT We report a case of AFS showing
      epithelial dysplasia arising in a recurrent AF in the left mandible after 3 years
      in a 26-year-old man, which is regarded as an uncommon histopathologic finding in
      AFS. We also emphasize the comprehensive clinical, radiographic, and
      histopathologic evaluation, and immunohistochemical staining of this patient.
      CONCLUSIONS We conclude that it is important to consider malignancy alternations
      in the epithelial component of AFS, along with that of the mesenchymal component,
      to provide a proper diagnosis and treatment of recurrent AF. 

PMID- 26289386
TI  - Xanthoma disseminatum: improvement in disfiguring facial lesions with cladribine.

PMID- 26289387
TI  - Facile graphene transfer directly to target substrates with a reusable metal
      catalyst.
AB  - High-throughput, roll-to-roll growth and transferring of high-quality, large-area
      chemical vapor deposited (CVD) graphene directly onto a target substrate with a
      reusable metal catalyst is an enabling technology for flexible optoelectronics.
      We explore the direct transfer via hot lamination of CVD graphene onto a flexible
      substrate, followed by electrochemical delamination (bubble transfer) of the
      graphene. The transfer method investigated here does not require any intermediate
      transfer layer and allows the copper to be reused, which will reduce the
      production cost and avoid the generation of chemical waste. Such integration is
      one necessary step forward toward the economical and industrial scale production
      of graphene. Our method bares promise in various applications. As an example, we
      fabricated flexible solution-gated graphene field-effect-transistors, which
      exhibited transconductance as high as 200 MUS. 

PMID- 26289385
TI  - Complement mediators: key regulators of airway tissue remodeling in asthma.
AB  - The complement mediators are the major effectors of the immune balance, which
      operates at the interface between the innate and adaptive immunity, and is vital
      for many immunoregulatory functions. Activation of the complement cascade through
      the classical, alternative or lectin pathways thus generating opsonins like C3b
      and C5b, anaphylatoxins C3a and C5a, chemotaxin, and inflammatory mediators,
      which leads to cellular death. Complement mediators that accelerate the airway
      remodeling are not well defined; however, an uncontrolled Th2-driven adaptive
      immune response has been linked to the major pathophysiologic features of asthma,
      including bronchoconstriction, airway hyperresponsiveness, and airway
      inflammation. The mechanisms leading to complement mediated airway tissue
      remodeling, and the effect of therapy on preventing and/or reversing it are not
      clearly understood. This review highlights complement-mediated inflammation, and
      the mechanism through it triggers the airway tissue injury and remodeling in the
      airway epithelium that could serve as potential targets for developing a new drug
      to rescue the asthma patients. 

PMID- 26289388
TI  - Protection of seven dibenzocyclooctadiene lignans from Schisandra chinensis
      against serum and glucose deprivation injury in SH-SY5Y cells.
AB  - Dibenzocyclooctadiene lignans, the major active components of fruit of Schisandra
      chinensis (Turcz.) Baill., have been found to have activities that could prevent
      prostate and thyroid cancer, hepatotoxicity, oxidative stress-induced cerebral
      injury, etc. This study was conducted to evaluate the effects of seven
      dibenzocyclooctadiene lignans of Schisandra chinensis and explore the possible
      mechanisms in the human neuroblastoma SH-SY5Y cells exposed on serum and glucose
      deprivation (SGD) injury. The structure-activity relationships were also
      analyzed. Cell viability and lactate dehydrogenase (LDH) release were determined
      to evaluate cell injury. Inflammation and apoptosis-related protein levels were
      detected to elucidate the possible mechanisms. Schisantherin A, schizandrin C,
      and schizandrol B were found to have stronger protective effects than schizandrin
      A, schizandrin B, and schisanhenol in SH-SY5Y cells against SGD injury. Moreover,
      the protective effects of these lignans were possibly exhibited by regulating
      inflammation and apoptosis-related proteins in SH-SY5Y cells after SGD injury,
      supporting their beneficial effects for the prevention of cell injury in the
      pathogenesis of the central nervous system diseases, including ischemia stroke.
      The number and position of hydroxyl group and methylenedioxy in these lignans may
      be required for their effects. 

PMID- 26289389
TI  - High-energy, stable and recycled molecular solar thermal storage materials using
      AZO/graphene hybrids by optimizing hydrogen bonds.
AB  - An important method for establishing a high-energy, stable and recycled molecular
      solar heat system is by designing and preparing novel photo-isomerizable
      molecules with a high enthalpy and a long thermal life by controlling molecular
      interactions. A meta- and ortho-bis-substituted azobenzene chromophore (AZO) is
      covalently grafted onto reduced graphene oxide (RGO) for solar thermal storage
      materials. High grafting degree and close-packed molecules enable intermolecular
      hydrogen bonds (H-bonds) for both trans-(E) and cis-(Z) isomers of AZO on the
      surface of nanosheets, resulting in a dramatic increase in enthalpy and lifetime.
      The metastable Z-form of AZO on RGO is thermally stabilized with a half-life of
      52 days by steric hindrance and intermolecular H-bonds calculated using density
      functional theory (DFT). The AZO-RGO fuel shows a high storage capacity of 138 Wh
      kg(-1) by optimizing intermolecular H-bonds with a good cycling stability for 50
      cycles induced by visible light at 520 nm. Our work opens up a new method for
      making advanced molecular solar thermal storage materials by tuning molecular
      interactions on a nano-template. 

PMID- 26289390
TI  - Insights from physiology into myometrial function and dysfunction.
AB  - NEW FINDINGS: What is the topic of this review? I focus on clinical aspects of
      uterine physiology, specifically, myometrial contractility. I bring together and
      contrast findings using physiological approaches and those using newer
      techniques, 'omics'. What advances does it highlight? Physiological studies have
      recently shed light on the myometrium in twin pregnancies, but there have been no
      'omic' approaches. In contrast, studies of preterm delivery using newer
      approaches are generating new research avenues, whereas traditional approaches
      have not flourished. Finally, I describe significant advances in understanding of
      'slow-to-progress' labours, achieved using physiological and clinical approaches.
      Advances in molecular, genetic and 'omic' technologies are fuelling the thirst
      for better understanding of the uterus and application of this information to
      problems in pregnancy and labour. Progress has, however, been limited while we
      still have an incomplete understanding of some of the basic physiology of uterine
      smooth muscle (myometrium). In this review and opinion piece, I explore some of
      the fascinating findings from selected recent studies and see how these may
      provide new avenues for physiological and clinical research. It is also the case,
      however, that there is still limited mechanistic understanding about
      physiological and pathophysiological processes in the myometrium. This lack of
      understanding limits the usefulness of some findings from genomic and allied
      studies. By focusing on some key recent findings and relating these to two
      important clinical problems in childbirth that involve myometrial activity,
      namely preterm delivery and difficult labours, the interplay between our
      physiological knowledge and the information provided by newer technologies is
      explored. My opinion is that physiology has provided much more new mechanistic
      insight into difficult births and that the newer technologies may lead to
      breakthroughs in preterm birth research, but that this has not yet happened.

PMID- 26289393
TI  - [Chronic primary pain disorders in children and adolescents].
AB  - AIM: Chronic and debilitating pediatric pain has a prevalence of 5% and as such
      constitutes a considerable health problem. The aim of this article is to provide
      an overview of current research activities on pediatric pain, available health
      care for children with chronic pain and education and training programs for
      health professionals. METHOD: This overview is based on the authors' personal
      experience, information available from medical, research and professional
      associations, as well as a PubMed literature search for the time period 2012-2015
      using "children";"pain" and "Germany" as search terms. RESULTS: There are
      numerous research activities in Germany focusing on the epidemiology, the
      underlying psychobiological mechanisms and on the multimodal treatment of chronic
      pediatric pain. This research is internationally widely acknowledged and makes a
      significant contribution to current developments in pediatric pain research. By
      contrast, health services and basic science research is clearly lacking in
      Germany. Moreover, specialized health care for youth with chronic pain is far
      less institutionalized when compared to adults suffering from chronic pain.
      Indeed, primary and secondary care services have rarely been studied or even
      evaluated. CONCLUSION: Similar to international trends, research on chronic
      pediatric pain has also grown and advanced in Germany. Indeed, not only the
      amount of research has increased but also its scope. Nonetheless, there is
      clearly a need for more research efforts with regard to the understanding of
      (pediatric) pain mechanisms, clinical studies and, especially, investigations on
      health care services. It is particularly important to focus on the
      implementation, improvement and systematic evaluation of specialized health care
      services which would be available and accessible for children and adolescents
      with chronic pain and not be restricted to tertiary care.

PMID- 26289392
TI  - Mudd's disease (MAT I/III deficiency): a survey of data for MAT1A homozygotes and
      compound heterozygotes.
AB  - BACKGROUND: This paper summarizes the results of a group effort to bring together
      the worldwide available data on patients who are either homozygotes or compound
      heterozygotes for mutations in MAT1A. MAT1A encodes the subunit that forms two
      methionine adenosyltransferase isoenzymes, tetrameric MAT I and dimeric MAT III,
      that catalyze the conversion of methionine and ATP to S-adenosylmethionine
      (AdoMet). Subnormal MAT I/III activity leads to hypermethioninemia. Individuals,
      with hypermethioninemia due to one of the MAT1A mutations that in heterozygotes
      cause relatively mild and clinically benign hypermethioninemia are currently
      often being flagged in screening programs measuring methionine elevation to
      identify newborns with defective cystathionine beta-synthase activity.
      Homozygotes or compound heterozygotes for MAT1A mutations are less frequent. Some
      but not all, such individuals have manifested demyelination or other CNS
      abnormalities. PURPOSE OF THE STUDY: The goals of the present effort have been to
      determine the frequency of such abnormalities, to find how best to predict
      whether they will occur, and to evaluate the outcomes of the variety of treatment
      regimens that have been used. Data have been gathered for 64 patients, of whom 32
      have some evidence of CNS abnormalities (based mainly on MRI findings), and 32 do
      not have such evidence. RESULTS AND DISCUSSION: The results show that mean plasma
      methionine concentrations provide the best indication of the group into which a
      given patient will fall: those with means of 800 MUM or higher usually have
      evidence of CNS abnormalities, whereas those with lower means usually do not.
      Data are reported for individual patients for MAT1A genotypes, plasma methionine,
      total homocysteine (tHcy), and AdoMet concentrations, liver function studies,
      results of 15 pregnancies, and the outcomes of dietary methionine restriction
      and/or AdoMet supplementation. Possible pathophysiological mechanisms that might
      contribute to CNS damage are discussed, and tentative suggestions are put forth
      as to optimal management.

PMID- 26289394
TI  - [Postoperative pain therapy in Germany. Status quo].
AB  - A great deal of progress has been made in the field of postoperative pain therapy
      in the last 20 years. Beginning from clinical trials on the effectiveness of
      individual procedures, such as epidural anesthesia and patient-controlled
      analgesia, a wide range of healthcare services research as well as basic research
      with human and animal experiments has been established. Whereas health services
      research in the 1980s and 1990s focused more on the implementation of acute pain
      services, outcome-oriented research approaches are nowadays the center of
      attention. Acute pain registries and pain certification projects initiated in
      Germany have to be mentioned particularly in this respect. Basic research papers
      from recent years increasingly address specific aspects of acute postoperative
      pain and have provided translational approaches that are applied around the world
      for studying neurobiological mechanisms of postoperative pain. At the same time,
      interdisciplinary cooperation in research projects has led to a better
      understanding of complex correlations regarding predictors and mechanisms
      (including psychosocial aspects) of acute and in recent times also chronic pain
      after surgery. In parallel, evidence-based medicine has found its way into acute
      pain medicine in Germany. In 2007, clinical acute pain therapy in Germany was
      enhanced by S3 level guidelines for the first time; however, the implementation
      is still incomplete. In future, questions concerning mechanism-based therapy of
      acute pain need to be equally in the center of attention of research, such as
      prevention of persisting pain after surgery and acute pain of different origins. 

PMID- 26289395
TI  - Coextensive Meningioma and Cholesterol Granuloma in the Forebrain of a Cat.

PMID- 26289396
TI  - Targeted prostate biopsy using magnetic resonance imaging-ultrasound fusion.
AB  - Prostate cancer is the second most common cancer among men worldwide, with an
      estimated 1.1 million new diagnoses and over 300,000 deaths reported in 2012 by
      the World Health Organization. A recent 5-year prevalence of the disease was
      nearly four million, far exceeding all other malignancies in men. Because of
      these numbers, efforts to improve early detection, accurate assessment of disease
      burden, and appropriate treatment options are important public health priorities.
      However, the basic tool for diagnosis, transrectal ultrasound (TRUS) guided
      biopsy, is flawed by failure to detect many serious cancers (>30% false negative
      rate)and over-detection of nonserious cancers. Multiparametric magnetic resonance
      imaging (mpMRI) of the prostate empowers the clinician to identify tumors that
      would otherwise be missed by conventional techniques and to record the precise
      locations of positive cores through targeted biopsy using MRI-ultrasound (MRI-US)
      fusion. As mpMRI advances and the level of experience for the user grows, the
      correlation between the level of suspicion for a prostate lesion and the MRI-US
      fusion targeted biopsy revealing malignancy improves. Consequently, the
      concordance among the targeted biopsy and surgical pathology rises. This in turn,
      allows the patient and provider to be confident that the therapeutic plan decided
      upon is representative of the true disease state.

PMID- 26289398
TI  - Multiple factors affecting surgical outcomes and patency rates in use of single
      armed two-suture microsurgical vasoepididymostomy: a single surgeon's experience
      with 81 patients.
AB  - Vasoepididymostomy (VE), as the most challenging procedure in microsurgeries, is
      often carried out with a double-armed two-suture technique. In this study, we
      evaluated the efficacy and safety of the single-armed two-suture VEs on humans
      and studied the factors that could possibly affect the patency rates. From July
      2012 to July 2013, we reviewed 81 patients with consecutive primary epididymal
      obstruction who underwent single-armed two-suture longitudinal intussusception
      microsurgical VEs by a single surgeon, Kai Hong (KH). At the same time, we
      analyzed seven factors that possibly related to the patency rates. With the
      single-armed technique, a total of 81 men underwent the microsurgical VEs. Data
      on 62 patients were completely recorded. 19 patients were lost to follow-up. Mean
      age was 31 years old. Mean follow-up time was 8.8 (2-17) months. The patency rate
      was 66.1% (41/62). Natural pregnancy rate was 34.1% (14/41). Overall pregnancy
      rate was 22.6% (14/62). No severe surgical complications were noted. With
      logistic regression test analysis, there were two factors related to a higher
      patency rate: anastomosis sites (P = 0.035) and motile sperm found in the
      epididymal fluid (P = 0.006). Motile sperm found in the epididymal fluid were
      associated with a higher patency rate (OR = 11.80, 95% CI = 1.79, 77.65). The
      single-armed two-suture longitudinal VE technique is feasible for microsurgical
      practice. The patency and pregnancy rates are comparable to the doubled-armed
      technique. Anastomosis sites and motile sperm found in the epididymal fluid were
      the most two important factors related to higher patency. 

PMID- 26289397
TI  - Vacuum therapy in penile rehabilitation after radical prostatectomy: review of
      hemodynamic and antihypoxic evidence.
AB  - Generally, hypoxia is a normal physiological condition in the flaccid penis,
      which is interrupted by regular nocturnal erections in men with normal erectile
      function. [1] Lack of spontaneous and nocturnal erections after radical
      prostatectomy due to neuropraxia results in persistent hypoxia of cavernosal
      tissue, which leads to apoptosis and degeneration of cavernosal smooth muscle
      fibers. Therefore, overcoming hypoxia is believed to play a crucial role during
      neuropraxia. The use of a vacuum erectile device (VED) in penile rehabilitation
      is reportedly effective and may prevent loss of penile length. The corporal blood
      after VED use is increased and consists of both arterial and venous blood, as
      revealed by color Doppler sonography and blood gas analysis. A similar phenomenon
      was observed in negative pressure wound therapy (NPWT). However, NPWT employs a
      lower negative pressure than VED, and a hypoperfused zone, which increases in
      response to negative pressure adjacent to the wound edge, was observed.
      Nonetheless, questions regarding ideal subatmospheric pressure levels, modes of
      action, and therapeutic duration of VED remain unanswered. Moreover, it remains
      unclear whether a hypoperfused zone or PO 2 gradient appears in the penis during
      VED therapy. To optimize a clinical VED protocol in penile rehabilitation,
      further research on the mechanism of VED, especially real-time PO 2 measurements
      in different parts of the penis, should be performed. 

PMID- 26289401
TI  - The presence of human papillomavirus and Epstein-Barr virus in male Chinese
      lichen sclerosus patients: a single center study.
AB  - This study aimed to investigate the presence of human papillomavirus and Epstein
      Barr virus in male lichen sclerosus patients. We extracted DNA from formalin
      fixed paraffin-embedded foreskin tissue blocks of 47 male LS patients and 30
      healthy men and performed real-time PCR test to detect HPV and EBV. None of the
      47 LS patients and 30 healthy men had detectable HPV infection. EBV was detected
      in 18 LS patients (38.3%) and four healthy men (13.3%), the difference is
      significant (P < 0.05). Tissue blocks with significant inflammatory reaction tend
      to have higher EBV load. HPV has no significant relationship with LS. Male LS
      patients have higher EBV infection rate, but the role of EBV in the pathogenesis
      of LS needs further investigate. 

PMID- 26289400
TI  - Annexin A5 regulates Leydig cell testosterone production via ERK1/2 pathway.
AB  - This study was to investigate the effect of annexin A5 on testosterone secretion
      from primary rat Leydig cells and the underlying mechanisms. Isolated rat Leydig
      cells were treated with annexin A5. Testosterone production was detected by
      chemiluminescence assay. The protein and mRNA of Steroidogenic acute regulatory
      (StAR), P450scc, 3beta-hydroxysteroid dehydrogenase (3beta-HSD), 17beta
      hydroxysteroid dehydrogenase (17beta-HSD), and 17alpha-hydroxylase were examined
      by Western blotting and semi-quantitative RT-PCR, respectively. Annexin A5
      significantly stimulated testosterone secretion from rat Leydig cells in dose-
      and time-dependent manners and increased mRNA and protein expression of StAR,
      P450scc, 3beta-HSD, and 17beta-HSD but not 17alpha-hydroxylase. Annexin A5
      knockdown by siRNA significantly decreased the level of testosterone and protein
      expression of P450scc, 3beta-HSD, and 17beta-HSD. The significant activation of
      ERK1/2 signaling was observed at 5, 10, and 30 min after annexin A5 treatment.
      After the pretreatment of Leydig cells with ERK inhibitor PD98059 (50 MUmol l-1 )
      for 20 min, the effects of annexin A5 on promoting testosterone secretion and
      increasing the expression of P450scc, 3beta-HSD, and 17beta-HSD were completely
      abrogated (P < 0.05). Thus, ERK1/2 signaling is involved in the roles of annexin
      A5 in mediating testosterone production and the expression of P450scc, 3beta-HSD,
      and 17beta-HSD in Leydig cells. 

PMID- 26289402
TI  - Bullying and harassment of trainees: an unspoken emergency?

PMID- 26289399
TI  - NODAL secreted by male germ cells regulates the proliferation and function of
      human Sertoli cells from obstructive azoospermia and nonobstructive azoospermia
      patients.
AB  - This study was designed to explore the regulatory effects of male germ cell
      secreting factor NODAL on Sertoli cell fate decisions from obstructive
      azoospermia (OA) and nonobstructive azoospermia (NOA) patients. Human Sertoli
      cells and male germ cells were isolated using two-step enzymatic digestion and
      SATPUT from testes of azoospermia patients. Expression of NODAL and its multiple
      receptors in human Sertoli cells and male germ cells were characterized by
      reverse transcription-polymerase chain reaction (RT-PCR) and immunochemistry.
      Human recombinant NODAL and its receptor inhibitor SB431542 were employed to
      probe their effect on the proliferation of Sertoli cells using the CCK-8 assay.
      Quantitative PCR and Western blots were utilized to assess the expression of
      Sertoli cell functional genes and proteins. NODAL was found to be expressed in
      male germ cells but not in Sertoli cells, whereas its receptors ALK4, ALK7, and
      ACTR-IIB were detected in Sertoli cells and germ cells, suggesting that NODAL
      plays a regulatory role in Sertoli cells and germ cells via a paracrine and
      autocrine pathway, respectively. Human recombinant NODAL could promote the
      proliferation of human Sertoli cells. The expression of cell cycle regulators,
      including CYCLIN A, CYCLIN D1 and CYCLIN E, was not remarkably affected by NODAL
      signaling. NODAL enhanced the expression of essential growth factors, including
      GDNF, SCF, and BMP4, whereas SB431542 decreased their levels. There was not
      homogeneity of genes changes by NODAL treatment in Sertoli cells from OA and
      Sertoli cell-only syndrome (SCO) patients. Collectively, this study demonstrates
      that NODAL produced by human male germ cells regulates proliferation and numerous
      gene expression of Sertoli cells. 

PMID- 26289403
TI  - Randomised controlled trial of a mobile phone infant resuscitation guide.
AB  - AIM: The aim of this study was to develop a mobile phone resuscitation guide
      (MPRG) and to evaluate its use during simulated resuscitation of a mannequin.
      METHODS: An MPRG was developed using EpiSurveyor. A randomised controlled trial
      was performed in school-going children aged 15-16 years. All subjects were taught
      infant CPR skills using the American Heart Association Infant CPR Anytime. Two
      weeks later, the students were randomised to use of MPRG or not, and their CPR
      skills were re-assessed. The assessment was conducted using previously validated
      checklists. RESULTS: Twenty-one students participated in this trial. The MPRG
      group performed notably better in the areas of calling emergency services (80%
      vs. 36.4%, P = 0.044), completing sufficient CPR cycles (90% vs. 45.5%, P =
      0.047) and following the correct CPR sequence (60% vs. 9.1%, P = 0.013). No
      difference in resuscitation skills of participants was observed. CONCLUSIONS: We
      have shown that participants were more likely to call emergency services if they
      were using the MPRG. Further trials are needed to investigate the utility of
      mobile phone guides and whether or not they can reduce the time taken to contact
      emergency services as well as if they can sustain correct CPR sequence in an in
      vivo setting.

PMID- 26289404
TI  - Algorithmic Approach for Removing the Redundancy in Diabetic Gene Categories
      Based on Semantic Similarity and Gene Expression Data.
AB  - Even after so much advancement in gene expression microarray technology, the main
      hindrance in analyzing microarray data is its limited number of samples as
      compared to a number of factors, which is a major impediment in revealing actual
      gene functionality and valuable information from the data. Analyzing gene
      expression data can indicate the factors which are differentially expressed in
      the diseased tissue. As most of these genes have no part to play in causing the
      disease of interest, thus, identification of disease-causing genes can reveal not
      just the case of the disease, but also its pathogenic mechanism. There are a lot
      of gene selection methods available which have the capacity to remove irrelevant
      genes, but most of them are not sufficient enough in removing redundancy in genes
      from microarray data, which increases the computational cost and decreases the
      classification accuracy. Combining the gene expression data with the gene
      ontology information can be helpful in determining the redundancy which can then
      be removed using the algorithm mentioned in the work. The gene list obtained
      after these sequential steps of the algorithm can be analyzed further to obtain
      the most deterministic genes responsible for type 2 diabetes. 

PMID- 26289405
TI  - In Silico Characterization and Analysis of RTBP1 and NgTRF1 Protein Through MD
      Simulation and Molecular Docking: A Comparative Study.
AB  - Gaining access to sequence and structure information of telomere-binding proteins
      helps in understanding the essential biological processes involve in conserved
      sequence-specific interaction between DNA and the proteins. Rice telomere-binding
      protein (RTBP1) and Nicotiana glutinosa telomere repeat binding factor (NgTRF1)
      are helix-turn-helix motif type of proteins that plays role in telomeric DNA
      protection and length regulation. Both the proteins share same type of domain,
      but till now there is very less communication on the in silico studies of these
      complete proteins. Here we intend to do a comparative study between two proteins
      through modeling of the complete proteins, physiochemical characterization, MD
      simulation and DNA-protein docking. I-TASSER and CLC protein work bench was
      performed to find out the protein 3D structure as well as the different
      parameters to characterize the proteins. MD simulation was completed by GROMOS
      forcefield of GROMACS for 10 ns of time stretch. The simulated 3D structures were
      docked with template DNA (3D DNA modeled through 3D-DART) of TTTAGGG conserved
      sequence motif using HADDOCK Web server. By digging up all the facts about the
      proteins, it was revealed that around 120 amino acids in the tail part were
      showing a good sequence similarity between the proteins. Molecular modeling,
      sequence characterization and secondary structure prediction also indicate the
      similarity between the protein's structure and sequence. The result of MD
      simulation highlights on the RMSD, RMSF, Rg, PCA and energy plots which also
      conveys the similar type of motional behavior between them. The best complex
      formation for both the proteins in docking result also indicates for the first
      interaction site which is mainly the helix3 region of the DNA-binding domain. The
      overall computational analysis reveals that RTBP1 and NgTRF1 proteins display
      good amount of similarity in their physicochemical properties, structure,
      dynamics and binding mode.

PMID- 26289406
TI  - Augmented Beta rectangular regression models: A Bayesian perspective.
AB  - Mixed effects Beta regression models based on Beta distributions have been widely
      used to analyze longitudinal percentage or proportional data ranging between zero
      and one. However, Beta distributions are not flexible to extreme outliers or
      excessive events around tail areas, and they do not account for the presence of
      the boundary values zeros and ones because these values are not in the support of
      the Beta distributions. To address these issues, we propose a mixed effects model
      using Beta rectangular distribution and augment it with the probabilities of zero
      and one. We conduct extensive simulation studies to assess the performance of
      mixed effects models based on both the Beta and Beta rectangular distributions
      under various scenarios. The simulation studies suggest that the regression
      models based on Beta rectangular distributions improve the accuracy of parameter
      estimates in the presence of outliers and heavy tails. The proposed models are
      applied to the motivating Neuroprotection Exploratory Trials in Parkinson's
      Disease (PD) Long-term Study-1 (LS-1 study, n = 1741), developed by The National
      Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson's
      Disease (NINDS NET-PD) network. 

PMID- 26289407
TI  - Open tubular capillary column for the separation of cytochrome C tryptic digest
      in capillary electrochromatography.
AB  - A silica capillary of 50 MUm internal diameter and 500 mm length (416 mm
      effective length) was chemically modified with 4-(trifluoromethoxy) phenyl
      isocyanate in the presence of dibutyl tin dichloride as catalyst. Sodium diethyl
      dithiocarbamate was reacted with the terminal halogen of the bound ligand to
      incorporate the initiator moiety, and in situ polymerization was performed using
      a monomer mixture of styrene, N-phenylacrylamide, and methacrylic acid. The
      resultant open tubular capillary column immobilized with the copolymer layer was
      used for the separation of tryptic digest of cytochrome C in capillary
      electrochromatography. The sample was well eluted and separated into many
      components. The elution patterns of tryptic digest of cytochrome C were studied
      with respect to pH and water content in the mobile phase. This preliminary study
      demonstrates that open tubular capillary electrochromatography columns with a
      modified copolymer layer composed of proper nonpolar and polar units fabricated
      by reversible addition-fragmentation transfer polymerization can be useful as
      separation media for proteomic analysis. 

PMID- 26289408
TI  - Anti-Vascular Endothelial Growth Factor Treatment Suppresses Early Brain Injury
      After Subarachnoid Hemorrhage in Mice.
AB  - The role of vascular endothelial growth factor (VEGF) in early brain injury (EBI)
      after subarachnoid hemorrhage (SAH) remains unclear. The aim of this study was to
      investigate effects of anti-VEGF therapy on EBI after SAH. C57BL/6 male mice
      underwent sham or filament perforation SAH modeling, and vehicle or two dosages
      (0.2 and 1 MUg) of anti-VEGF antibody were randomly administrated by an
      intracerebroventricular injection. Neuroscore, brain water content,
      immunoglobulin G staining, and Western blotting were performed to evaluate EBI at
      24-48 h. To confirm the role of VEGF, anti-VEGF receptor (VEGFR)-2 (a major
      receptor of VEGF) antibody was intracerebroventricularly administered and the
      effects on EBI were evaluated at 24 h. A higher dose, but not a lower dose, of
      anti-VEGF antibody significantly ameliorated post-SAH neurological impairments
      and brain edema at 24-48 h post-SAH. Post-SAH blood-brain barrier disruption was
      also inhibited by anti-VEGF antibody. The protective effects of anti-VEGF
      antibody were associated with the inhibition of post-SAH induction of VEGF, VEGFR
      2, phosphorylated VEGFR-2, interleukin-1beta and a matricellular protein tenascin
      C (TNC). Anti-VEGFR-2 antibody also suppressed post-SAH neurological impairments
      and brain edema associated with VEGFR-2 inactivation and TNC downregulation.
      These findings demonstrated that VEGF causes post-SAH EBI via VEGFR-2 and TNC and
      that anti-VEGF therapy is effective for post-SAH EBI.

PMID- 26289409
TI  - Pharmacogenetic Study on the Impact of Rivastigmine Concerning Genetic Variants
      of A2M and IL-6 Genes on Iranian Alzheimer's Patients.
AB  - Alzheimer's disease (AD) is a polygenic and multifactorial disease with a complex
      inheritance caused by the formation of amyloid plaques and neurofibrillary
      tangles in the brain. Increasing evidence indicates that many genes including
      interleukin-6 (IL-6) and alpha 2-macroglobulin (A2M) may contribute to the
      pathogenesis of AD. The A2M gene encodes alpha2-macroglobulin which specifically
      binds with the beta-amyloid peptides and prevents fibril formation. Protein of
      the IL-6 gene linked to beta-amyloid (betaA) aggregation was detected in betaA
      plaques in the brain of AD patients. The aim of the present study is to
      investigate the relationship of the IL-6 and A2M gene polymorphisms with AD and
      also the impact of rivastigmine on AD patients regarding their genotypes on IL-6
      and A2M genes in 150 Iranian AD patients under rivastigmine therapy and 150
      matched healthy controls. The results indicated that IL-6 G and C alleles had
      significant positive and negative association with AD, respectively, (P = 0.0001,
      relative risks (RR) = 1.39) and frequency of AD patients carrying IL-6 GG
      genotype was significantly in higher proportion in familial Alzheimer's disease
      (FAD) patients compared to controls (P = 0.02, RR = 2.25), and the IL-6 CC
      genotype was significantly protective against AD (P = 0.0003, RR = 0.65).
      Genotype analysis of A2M gene showed a significant positive correlation between
      A2M AA genotype and the AD patients (sporadic Alzheimer's disease (SAD) and FAD)
      (P = 0.001, RR = 1.56), proposing it as a possible risk factor for AD. Drug
      response from pharmacogenetic viewpoint after 3-year follow-up of AD patients and
      Clinical Dementia Rating (CDR) analysis demonstrated that AD patients carrying
      bigenic genotype IL-6 CC-A2M AG (DeltaCDR = 4.5) and male patients with IL-6 CC
      genotype (DeltaCDR = 3.83) provided the best response and the A2M GG genotype
      (DeltaCDR = 7.97) and bigenic genotype IL-6 GG-A2M GG (DeltaCDR = 8.5) conferred
      the worst response to the rivastigmine, suggesting likely involvement of genotype
      specific response to rivastigmine therapy in AD patients. The results also
      propose that in view of the fact that C and G alleles created by nucleotide
      changes in the promoter region of IL-6 gene and this may affect the expression of
      the IL-6 gene and, hence, susceptible and protective role of GG and CC genotype
      in AD might be caused by higher and lower expression of IL-6 cytokine,
      respectively.

PMID- 26289410
TI  - Effect of native vitamin D3 supplementation on refractory chronic hepatitis C
      patients in simeprevir with pegylated interferon/ribavirin.
AB  - AIM: Protease inhibitors with pegylated interferon (PEG IFN)/ribavirin improve a
      sustained virological response (SVR) rate to approximately 90% in chronic
      hepatitis C genotype 1b patients with IL28B rs8099917 genotype TT, but yield only
      approximately 50% in those with the unfavorable non-TT. Among such treatment
      refractory patients, serum vitamin D levels could influence the SVR rate. This
      randomized controlled trial was conducted to assess the effect of native vitamin
      D supplementation in simeprevir with PEG IFN/ribavirin for 1b patients with non
      TT. METHODS: Patients were randomly assigned to receive simeprevir (100 mg/day)
      for 12 weeks plus PEG IFN/ribavirin for 24 weeks (control group, n = 58), or
      vitamin D (2000 IU/day) for 16 weeks including a lead-in phase plus PEG
      IFN/ribavirin for 24 weeks (vitamin D group, n = 57). The primary end-point was
      sustainably undetectable viremia 24 weeks after the end of treatment (SVR).
      RESULTS: SVR rates were 37.9% in the control group and 70.2% in the vitamin D
      group. In subgroup analysis, SVR rates of prior null responders were 11.8% and
      54.5%, respectively. SVR rates for advanced fibrosis were 28.6% and 65.4%. SVR
      rates for patients with vitamin D3 deficiency at the baseline were 25.0% in the
      control group and 66.7% in the vitamin D group. Overall, the SVR rate was
      significantly higher in patients with high serum 25(OH)D3 levels at the beginning
      of combination therapy than in those with low serum 25(OH)D3 levels. CONCLUSION:
      Native vitamin D3 supplementation improved SVR rates in simeprevir with PEG
      IFN/ribavirin for chronic hepatitis C genotype 1b patients with refractory
      factors.

PMID- 26289411
TI  - Doubling Power Output of Starch Biobattery Treated by the Most Thermostable
      Isoamylase from an Archaeon Sulfolobus tokodaii.
AB  - Biobattery, a kind of enzymatic fuel cells, can convert organic compounds (e.g.,
      glucose, starch) to electricity in a closed system without moving parts. Inspired
      by natural starch metabolism catalyzed by starch phosphorylase, isoamylase is
      essential to debranch alpha-1,6-glycosidic bonds of starch, yielding linear
      amylodextrin - the best fuel for sugar-powered biobattery. However, there is no
      thermostable isoamylase stable enough for simultaneous starch gelatinization and
      enzymatic hydrolysis, different from the case of thermostable alpha-amylase. A
      putative isoamylase gene was mined from megagenomic database. The open reading
      frame ST0928 from a hyperthermophilic archaeron Sulfolobus tokodaii was cloned
      and expressed in E. coli. The recombinant protein was easily purified by heat
      precipitation at 80 (o)C for 30 min. This enzyme was characterized and required
      Mg(2+) as an activator. This enzyme was the most stable isoamylase reported with
      a half lifetime of 200 min at 90 (o)C in the presence of 0.5 mM MgCl2, suitable
      for simultaneous starch gelatinization and isoamylase hydrolysis. The cuvett
      based air-breathing biobattery powered by isoamylase-treated starch exhibited
      nearly doubled power outputs than that powered by the same concentration starch
      solution, suggesting more glucose 1-phosphate generated. 

PMID- 26289412
TI  - An Appeal to Standardize CT- and MR-Perfusion.
AB  - Multiple treatment options and risk assessment in cerebrovascular diseases are
      the actual challenges in diagnostic as well as in interventional
      neuroradiology.Acute ischemic stroke essentially requires rapid detection of the
      location and extent of infarction and tissue at risk for making treatment
      decisions. In the acute setting, modern multiparametric perfusion imaging
      protocols help to determine infarct core and adjacent penumbral tissue, and they
      enable the estimation of collateral flow of intra- and extracranial arteries. In
      subacute delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) or
      chronic occlusive neurovascular diseases estimation of residual and collateral
      flow may be even more difficult.Prediction of sufficient or insufficient supply
      of brain tissue may be essential to balance conservative against interventional
      therapies. However, so far no established reliable thresholds are available for
      determining tissue at acute, subacute, chronic progressive, or chronic
      risk.Reliable and reproducible thresholds require quantitative perfusion
      measurements with a calibrated instrument. But the measurement instrument is not
      at all defined-a variety of parameter settings, different algorithms based on
      multiple assumptions and a wide variety of published normal and pathologic values
      for perfusion parameters indicate the problem. In the following text, we explain
      how deep the problem may be enrooted within techniques and algorithms impeding
      broad use of perfusion for many clinical issues. 

PMID- 26289413
TI  - Inference of biogeographical ancestry across central regions of Eurasia.
AB  - The inference of biogeographical ancestry (BGA) can provide useful information
      for forensic investigators when there are no suspects to be compared with DNA
      collected at the crime scene or when no DNA database matches exist. Although
      public databases are increasing in size and population scope, there is a lack of
      information regarding genetic variation in Eurasian populations, especially in
      central regions such as the Middle East. Inhabitants of these regions show a high
      degree of genetic admixture, characterized by an allele frequency cline running
      from NW Europe to East Asia. Although a proper differentiation has been
      established between the cline extremes of western Europe and South Asia,
      populations geographically located in between, i.e, Middle East and Mediterranean
      populations, require more detailed study in order to characterize their genetic
      background as well as to further understand their demographic histories. To
      initiate these studies, three ancestry informative SNP (AI-SNP) multiplex panels:
      the SNPforID 34-plex, Eurasiaplex and a novel 33-plex assay were used to describe
      the ancestry patterns of a total of 24 populations ranging across the
      longitudinal axis from NW Europe to East Asia. Different ancestry inference
      approaches, including STRUCTURE, PCA, DAPC and Snipper Bayes analysis, were
      applied to determine relationships among populations. The structure results show
      differentiation between continental groups and a NW to SE allele frequency cline
      running across Eurasian populations. This study adds useful population data that
      could be used as reference genotypes for future ancestry investigations in
      forensic cases. The 33-plex assay also includes pigmentation predictive SNPs, but
      this study primarily focused on Eurasian population differentiation using 33-plex
      and its combination with the other two AI-SNP sets. 

PMID- 26289414
TI  - Sex estimation from measurements of the first rib in a contemporary Polish
      population.
AB  - The aim of this study was to evaluate the accuracy of sex assessment using
      measurements of the first rib from computed tomography (CT) to develop a
      discriminant formula. Four discriminant formulae were derived based on CT imaging
      of the right first rib of 85 female and 91 male Polish patients of known age and
      sex. In direct discriminant analysis, the first equation consisted of all first
      rib variables; the second included measurements of the rib body; the third
      comprised only two measurements of the sternal end of the first rib. The stepwise
      method selected the four best variables from all measurements. The discriminant
      function equation was then tested on a cross-validated group consisting of 23
      females and 24 males. The direct discriminant analysis showed that sex assessment
      was possible in 81.5% of cases in the first group and in 91.5% in the cross
      validated group when all variables for the first rib were included. The average
      accuracy for the original group for rib body and sternal end was 80.9 and 67.9%,
      respectively. The percentages of correctly assigned individuals for the functions
      based on the rib body and sternal end in the cross-validated group were 76.6 and
      85.0%, respectively. Higher average accuracies were obtained for stepwise
      discriminant analysis: 83.1% for the original group and 91.2% for the cross
      validated group. The exterior edge, anterior-posterior of the sternal end, and
      depth of the arc were the most reliable parameters. Our results suggest that the
      first rib is dimorphic and that the described method can be used for sex
      assessment.

PMID- 26289415
TI  - Assessment of IrisPlex-based multiplex for eye and skin color prediction with
      application to a Portuguese population.
AB  - DNA phenotyping research is one of the most emergent areas of forensic genetics.
      Predictions of externally visible characteristics are possible through analysis
      of single nucleotide polymorphisms. These tools can provide police with
      "intelligence" in cases where there are no obvious suspects and unknown
      biological samples found at the crime scene do not result in any criminal DNA
      database hits. IrisPlex, an eye color prediction assay, revealed high prediction
      rates for blue and brown eye color in European populations. However, this is less
      predictive in some non-European populations, probably due to admixing. When
      compared to other European countries, Portugal has a relatively admixed
      population, resulting from a genetic influx derived from its proximity to and
      historical relations with numerous African territories. The aim of this work was
      to evaluate the utility of IrisPlex in the Portuguese population. Furthermore,
      the possibility of supplementing this multiplex with additional markers to also
      achieve skin color prediction within this population was evaluated. For that,
      IrisPlex was augmented with additional SNP loci. Eye and skin color prediction
      was estimated using the multinomial logistic regression and binomial logistic
      regression models, respectively. The results demonstrated eye color prediction
      accuracies of the IrisPlex system of 90 and 60% for brown and blue eye color,
      respectively, and 77% for intermediate eye color, after allele frequency
      adjustment. With regard to skin color, it was possible to achieve a prediction
      accuracy of 93%. In the future, phenotypic determination multiplexes must include
      additional loci to permit skin color prediction as presented in this study as
      this can be an advantageous tool for forensic investigation.

PMID- 26289416
TI  - Whole mitochondrial genome genetic diversity in an Estonian population sample.
AB  - Mitochondrial DNA is a useful marker for population studies, human
      identification, and forensic analysis. Commonly used hypervariable regions I and
      II (HVI/HVII) were reported to contain as little as 25% of mitochondrial DNA
      variants and therefore the majority of power of discrimination of mitochondrial
      DNA resides in the coding region. Massively parallel sequencing technology
      enables entire mitochondrial genome sequencing. In this study, buccal swabs were
      collected from 114 unrelated Estonians and whole mitochondrial genome sequences
      were generated using the Illumina MiSeq system. The results are concordant with
      previous mtDNA control region reports of high haplogroup HV and U frequencies
      (47.4 and 23.7% in this study, respectively) in the Estonian population. One
      sample with the Northern Asian haplogroup D was detected. The genetic diversity
      of the Estonian population sample was estimated to be 99.67 and 95.85%, for
      mtGenome and HVI/HVII data, respectively. The random match probability for
      mtGenome data was 1.20 versus 4.99% for HVI/HVII. The nucleotide mean pairwise
      difference was 27 +/- 11 for mtGenome and 7 +/- 3 for HVI/HVII data. These data
      describe the genetic diversity of the Estonian population sample and emphasize
      the power of discrimination of the entire mitochondrial genome over the
      hypervariable regions.

PMID- 26289417
TI  - Using multiple online databases to help identify microRNAs regulating the airway
      epithelial cell response to a virus-like stimulus.
AB  - BACKGROUND AND OBJECTIVE: Exacerbations of allergic asthma are often triggered by
      respiratory viral infections. We have previously shown that in a T-helper type 2
      (Th2)-biased cytokine environment, mouse and human airway epithelial cells (AEC)
      exhibit increased expression of pro-inflammatory and anti-viral genes in response
      to synthetic double-stranded ribonucleic acid (dsRNA), a virus-like stimulus.
      This implies coordinated regulation of gene expression, suggesting possible
      involvement of microRNA. To investigate this, we developed a novel approach to
      identifying candidate microRNA using online databases, then confirmed their
      expression by quantitative real-time polymerase chain reaction (qRT-PCR).
      METHODS: Using a list of genes of interest, defined on the basis of the previous
      study as being up-regulated in a Th2 environment, we searched mouse and human
      microRNA databases for possible regulatory microRNA, and selected 10 candidates
      that were conserved across species or predicted by more than one human database.
      Expression of these microRNA was tested by qRT-PCR, in primary human AEC pre
      treated with Th2 cytokines and exposed to dsRNA. RESULTS: Expression of hsa-miR
      139-5p, miR-423-5p and miR-542-3p was significantly decreased in Th2 pre-treated
      AEC, and miR-135a-5p exhibited a trend towards decreased expression. Further
      database searches confirmed that these microRNA regulated additional pro
      inflammatory and anti-viral response genes for which expression had previously
      been shown to be up-regulated, confirming the validity of this approach.
      CONCLUSIONS: Our study demonstrates the value of using multiple online databases
      to identify candidate regulatory microRNA and provides the first evidence that in
      an allergic environment, microRNA may be important in altering the pro
      inflammatory and anti-viral responses of human AEC during exacerbations of
      asthma.

PMID- 26289418
TI  - Prognostic value of kidney biopsy in myeloma cast nephropathy: a retrospective
      study of 70 patients.
AB  - BACKGROUND: Light chain myeloma cast nephropathy (MCN) is the major cause of
      renal failure in multiple myeloma and strongly impacts patient survival. The role
      of kidney biopsy in the management of MCN is unclear. METHODS: Renal pathological
      findings were retrospectively studied in 70 patients with multiple myeloma and
      MCN. Patients were categorized according to the achievement or not of renal
      response, as defined by estimated glomerular filtration rate (eGFR) >= 30
      mL/min/1.73 m(2) and/or dialysis independence at 3 months. RESULTS: Thirty-two
      patients (46%) achieved a renal response. In the whole study population, the
      following parameters differed significantly between patients with and without
      renal response, respectively: baseline median eGFR (13.3 versus 9.3 mL/min/1.73
      m(2), P = 0.017), Acute Kidney Injury Network Stage 3 (68.8 versus 92.1%, P =
      0.019), haematological response rate (94 versus 34%, P < 0.0001), median
      percentage of free light chain (FLC) reduction at Day 21 (92 versus 24%, P =
      0.006) and median number of casts/10 fields (14 versus 25, P = 0.005). The extent
      of interstitial fibrosis and tubular atrophy was similar. In multivariate
      analysis, only FLC reduction at Day 21 was significantly associated with renal
      response. However, when considering only the subgroup of haematological
      responders, both median number of casts [odds ratio (OR) = 0.93, 95% confidence
      interval (95% CI): 0.88-0.98, P = 0.01] and extent of tubular atrophy (OR = 0.03,
      95% CI: 0.00-0.52, P = 0.02) were independent predictors of renal response.
      CONCLUSIONS: In MCN, the presence of numerous casts and diffuse tubular atrophy
      is associated with poor renal prognosis. These data suggest that additional
      strategies to reduce FLC burden should be considered in patients with extensive
      cast formation.

PMID- 26289419
TI  - Comparison of two treatments with skewed ordinal responses.
AB  - In clinical studies, the proportional odds model is widely used to compare
      treatment efficacies when the responses are categorically ordered. However, this
      model has been shown to be inappropriate when the proportional odds assumption is
      invalid, mainly because it is unable to control the type I error rate in such
      circumstances. To remedy this problem, the latent normal model was recently
      promoted and has been demonstrated to be superior to the proportional odds model.
      However, the application of the latent normal model is limited to compare
      treatments with similar underlying distributions except possibly their means and
      variances. When the underlying distributions are very different in skewness, both
      of the aforementioned procedures suffer from the undesirable inflation of the
      type I error rate. To solve the problem for clinical studies with ordinal
      responses, we provide a viable solution that relies on the use of the latent
      Weibull distribution, which is a member of the log-location-scale family. The
      proposed model is able to control the type I error rate regardless of the degree
      of skewness of the treatment responses. In addition, the power of the test also
      outperforms that of the latent normal model. The testing procedure draws on newly
      developed theoretical results related to latent distributions from the location
      scale family. The testing procedure is illustrated with two clinical examples.

PMID- 26289420
TI  - Tropical leg ulcers in children: more than yaws.
AB  - The management of yaws has changed in recent years. Mass treatment with oral
      azithromycin has replaced intramuscular benzathine benzylpenicillin. Treponemal
      and non-treponemal serology (equivalent to TPHA and RPR) point-of-care blood
      testing is now available. In addition, recent studies in yaws endemic regions
      have shown that a significant number of leg ulcers in children which are
      clinically suggestive of yaws are caused by Haemophilus ducreyi. It is noteworthy
      that the World Health Organization has also set the ambitious goal to eliminate
      yaws by 2020.

PMID- 26289421
TI  - Screening strategies for colorectal cancer among patients with nonalcoholic fatty
      liver disease and family history.
AB  - Patients with nonalcoholic fatty liver disease (NAFLD) and family history of
      colorectal cancer (CRC) are at higher risks but how they should be screened
      remains uncertain. Hence, we evaluated the cost-effectiveness of CRC screening
      among patients with NAFLD and family history by different strategies. A
      hypothetical population of 100,000 subjects aged 40-75 years receive: (i) yearly
      fecal immunochemical test (FIT) at 50 years; (ii) flexible sigmoidoscopy (FS)
      every 5 years at 50 years; (iii) colonoscopy 10 yearly at 50 years; (iv)
      colonoscopy 10 yearly at 50 years among those with family history/NAFLD and
      yearly FIT at 50 years among those without; (v) colonoscopy 10 yearly at 40 years
      among those with family history/NAFLD and yearly FIT at 50 years among those
      without and (vi) colonoscopy 10 yearly at 40 years among those with family
      history/NAFLD and colonoscopy 10 yearly at 50 years among those without. The
      incremental cost-effectiveness ratio (ICER) was studied by Markov modeling. It
      was found that colonoscopy, FS and FIT reduced incidence of CRC by 49.5, 26.3 and
      23.6%, respectively. Using strategies 4, 5 and 6, the corresponding reduction in
      CRC incidence was 29.9, 30.9 and 69.3% for family history, and 33.2, 34.7 and
      69.8% for NAFLD. Compared with no screening, strategies 4 (US$1,018/life-year
      saved) and 5 (US$7,485) for family history offered the lowest ICER, whilst
      strategy 4 (US$5,877) for NAFLD was the most cost-effective. These findings were
      robust when assessed with a wide range of deterministic sensitivity analyses
      around the base case. These indicated that screening patients with family history
      or NAFLD by colonoscopy at 50 years was economically favorable. 

PMID- 26289422
TI  - Water-soluble chlorophyll-binding proteins from Arabidopsis thaliana and Raphanus
      sativus target the endoplasmic reticulum body.
AB  - BACKGROUND: Non-photosynthetic chlorophyll (Chl) proteins called water-soluble
      Chl-binding proteins are distributed in Brassicaceae plants. Brassica oleracea
      WSCP (BoWSCP) and Lepidium virginicum WSCP (LvWSCP) are highly expressed in
      leaves and stems, while Arabidopsis thaliana WSCP (AtWSCP) and Raphanus sativus
      WSCP (RshWSCP) are highly transcribed in floral organs. BoWSCP and LvWSCP exist
      in the endoplasmic reticulum (ER) body. However, the subcellular localization of
      AtWSCP and RshWSCP is still unclear. To determine the subcellular localization of
      these WSCPs, we constructed transgenic plants expressing Venus-fused AtWSCP or
      RshWSCP. RESULTS: Open reading frames corresponding to full-length AtWSCP and
      RshWSCP were cloned and ligated between the cauliflower mosaic virus 35S promoter
      and Venus, a gene encoding a yellow fluorescent protein. We introduced the
      constructs into A. thaliana by the floral dip method. We succeeded in
      constructing a number of transformants expressing Venus-fused chimeric AtWSCP
      (AtWSCP::Venus) or RshWSCP (RshWSCP::Venus). We detected fluorescence derived
      from the chimeric proteins using a fluorescence microscope system. In cotyledons,
      fluorescence derived from AtWSCP::Venus and RshWSCP::Venus was detected in
      spindle structures. The spindle structures altered their shape to a globular form
      under blue light excitation. In true leaves, the number of spindle structures was
      drastically reduced. These observations indicate that the spindle structure was
      the ER body. CONCLUSIONS: AtWSCP and RshWSCP have the potential for ER body
      targeting like BoWSCP and LvWSCP.

PMID- 26289423
TI  - Prevalence of atrial tachyarrhythmia in adults after Fontan operation.
AB  - OBJECTIVES: The Fontan procedure provides palliation for patients with complex
      congenital heart disease. A late complication is the development of a pro
      arrhythmogenic environment. Modifications to the surgical technique try and
      reduce the incidence of late arrhythmia. This study aims to establish incidence
      and outcome of arrhythmias in Fontan patients with long-term follow-up. METHODS:
      Retrospective analysis of adult patients with a Fontan circulation cared for by
      University Hospitals Birmingham between 2001 and 2013. RESULTS: 166 patients,
      mean age 29.1 years, were identified (63% atriopulmonary (AP) Fontan, 13% lateral
      tunnel (LT), 24% extracardiac total cavopulmonary connection (TCPC)). The mean
      follow-up since Fontan surgery was 18.6 years. 42% (70 patients) had suffered at
      least one tachyarrhythmia, with 100% incidence of arrhythmia in AP Fontan
      patients surviving at least 26 years following surgery. The most common
      arrhythmia was intra-atrial re-entrant tachycardia (66%). There was also a
      significant incidence of arrhythmia in the LT and TCPC groups (23% at mean follow
      up of 19.6 years and 13.6 years, respectively). 44 patients had undergone
      electrical cardioversion, 30 had ablations and 10 had undergone Fontan conversion
      surgery. Survival analysis showed only age at the time of Fontan as a significant
      predictor for arrhythmia onset (p<0.001) irrespective of surgical approach.
      CONCLUSIONS: There is a significant, increasing arrhythmia burden in adult
      patients with a Fontan circulation. Arrhythmia development could be regarded as
      an inevitable consequence of an AP Fontan. There remains a high incidence of
      arrhythmia with more modern surgical approaches. The long-term future of these
      patients is unclear and their care poses significant challenges.

PMID- 26289424
TI  - Systematics and historical biogeography of the old world butterfly subtribe
      Mycalesina (Lepidoptera: Nymphalidae: Satyrinae).
AB  - BACKGROUND: Butterflies of the subtribe Mycalesina have radiated successfully in
      almost all habitat types in Africa, Madagascar, the Indian subcontinent, Indo
      China and Australasia. Studies aimed at understanding the reasons behind the
      evolutionary success of this spectacular Old World butterfly radiation have been
      hampered by the lack of a stable phylogeny for the group. Here, we have
      reconstructed a robust phylogenetic framework for the subtribe using 10 genes
      from 195 exemplar taxa. RESULTS: We recovered seven well supported clades within
      the subtribe corresponding to the five traditional genera (Lohora, Heteropsis,
      Hallelesis, Bicyclus, Mycalesis), one as recently revised (Mydosama) and one
      newly revised genus (Culapa). The phylogenetic relationships of these mycalesine
      genera have been robustly established for the first time. Within the proposed
      phylogenetic framework, we estimated the crown age of the subtribe to be 40
      Million years ago (Mya) and inferred its ultimate origin to be in Asia. Our
      results reveal both vicariance and dispersal as factors responsible for the
      current widespread distribution of the group in the Old World tropics. We
      inferred that the African continent has been colonized at least twice by Asian
      mycalesines within the last 26 and 23 Mya. In one possible scenario, an Asian
      ancestor gave rise to Heteropsis on continental Africa, which later dispersed
      into Madagascar and most likely back colonised Asia. The second colonization of
      Africa by Asian ancestors resulted in Hallelesis and Bicyclus on continental
      Africa, the descendants of which did not colonise other regions but rather
      diversified only in continental Africa. The genera Lohora and Mydosama are
      derivatives of ancestors from continental Asia. CONCLUSION: Our proposed time
      calibrated phylogeny now provides a solid framework within which we can implement
      mechanistic studies aimed at unravelling the ecological and evolutionary
      processes that culminated in the spectacular radiation of mycalesines in the Old
      World tropics.

PMID- 26289425
TI  - Combining behavioural activation with physical activity promotion for adults with
      depression: findings of a parallel-group pilot randomised controlled trial
      (BAcPAc).
AB  - BACKGROUND: Depression is associated with physical inactivity, which may mediate
      the relationship between depression and a range of chronic physical health
      conditions. However, few interventions have combined a psychological intervention
      for depression with behaviour change techniques, such as behavioural activation
      (BA), to promote increased physical activity. METHODS: To determine procedural
      and clinical uncertainties to inform a definitive randomised controlled trial
      (RCT), a pilot parallel-group RCT was undertaken within two Improving Access to
      Psychological Therapies (IAPT) services in South West England. We aimed to
      recruit 80 adults with depression and randomise them to a supported, written self
      help programme based on either BA or BA plus physical activity promotion
      (BAcPAc). Data were collected at baseline and 4 months post-randomisation to
      evaluate trial retention, intervention uptake and variance in outcomes to inform
      a sample size calculation. Qualitative data were collected from participants and
      psychological wellbeing practitioners (PWPs) to assess the acceptability and
      feasibility of the trial methods and the intervention. Routine data were
      collected to evaluate resource use and cost. RESULTS: Sixty people with
      depression were recruited, and a 73 % follow-up rate was achieved. Accelerometer
      physical activity data were collected for 64 % of those followed. Twenty
      participants (33 %) attended at least one treatment appointment. Interview data
      were analysed for 15 participants and 9 study PWPs. The study highlighted the
      challenges of conducting an RCT within existing IAPT services with high staff
      turnover and absences, participant scheduling issues, PWP and participant
      preferences for cognitive focussed treatment, and deviations from BA delivery
      protocols. The BAcPAc intervention was generally acceptable to patients and PWPs.
      CONCLUSIONS: Although recruitment procedures and data collection were
      challenging, participants generally engaged with the BAcPAc self-help booklets
      and reported willingness to increase their physical activity. A number of
      feasibility issues were identified, in particular the under-use of BA as a
      treatment for depression, the difficulty that PWPs had in adapting their existing
      procedures for study purposes and the instability of the IAPT PWP workforce.
      These problems would need to be better understood and resolved before proceeding
      to a full-scale RCT. TRIAL REGISTRATION: ISRCTN74390532 . Registered on 26 March
      2013.

PMID- 26289426
TI  - Parents' perception of stroller use in young children: a qualitative study.
AB  - BACKGROUND: Despite their wide usage, it has recently been suggested that
      stroller use may reduce physical activity levels of young children. However,
      there have been no studies on stroller use as it relates to physical activity
      outcomes. The objectives of this study were to understand the context of stroller
      use for young children and parents' perceptions of the relationship between
      stroller use and their children's physical activity. METHODS: Parents of children
      1 to 5 years of age were recruited through two sites of TARGet Kids!, a primary
      care, practice-based research network in Toronto, Canada. Fourteen semi
      structured interviews were conducted. Interviews were audio recorded and
      transcribed verbatim and two independent reviewers conducted thematic analysis. A
      number of strategies were employed to ensure the trustworthiness of the data.
      RESULTS: Parents discussed reasons for stroller use (i.e., transportation;
      storage; leisure; supervision/confinement; parent physical activity; and sleep),
      factors that influence the decision to use a stroller (i.e., caregiver choice;
      convenience, timing, distance; family lifestyle; and child preference), and
      perceived impact of stroller use on physical activity (i.e., most parents did not
      recognize a connection between stroller use and physical activity). CONCLUSION:
      This study provides a context for researchers and policy makers to consider when
      developing stroller related physical activity guidelines for young children.

PMID- 26289427
TI  - CicArVarDB: SNP and InDel database for advancing genetics research and breeding
      applications in chickpea.
AB  - Molecular markers are valuable tools for breeders to help accelerate crop
      improvement. High throughput sequencing technologies facilitate the discovery of
      large-scale variations such as single nucleotide polymorphisms (SNPs) and simple
      sequence repeats (SSRs). Sequencing of chickpea genome along with re-sequencing
      of several chickpea lines has enabled the discovery of 4.4 million variations
      including SNPs and InDels. Here we report a repository of 1.9 million variations
      (SNPs and InDels) anchored on eight pseudomolecules in a custom database,
      referred as CicArVarDB that can be accessed at http://cicarvardb.icrisat.org/. It
      includes an easy interface for users to select variations around specific regions
      associated with quantitative trait loci, with embedded webBLAST search and
      JBrowse visualisation. We hope that this database will be immensely useful for
      the chickpea research community for both advancing genetics research as well as
      breeding applications for crop improvement. Database URL:
      http://cicarvardb.icrisat.org.

PMID- 26289428
TI  - FlyVar: a database for genetic variation in Drosophila melanogaster.
AB  - FlyVar is a publicly and freely available platform that addresses the increasing
      need of next generation sequencing data analysis in the Drosophila research
      community. It is composed of three parts. First, a database that contains 5.94
      million DNA polymorphisms found in Drosophila melanogaster derived from whole
      genome shotgun sequencing of 612 genomes of D. melanogaster. In addition, a list
      of 1094 dispensable genes has been identified. Second, a graphical user interface
      (GUI) has been implemented to allow easy and flexible queries of the database.
      Third, a set of interactive online tools enables filtering and annotation of
      genomic sequences obtained from individual D. melanogaster strains to identify
      candidate mutations. FlyVar permits the analysis of next generation sequencing
      data without the need of extensive computational training or resources. Database
      URL: www.iipl.fudan.edu.cn/FlyVar.

PMID- 26289429
TI  - Association between left ventricular global longitudinal strain and natriuretic
      peptides in outpatients with chronic systolic heart failure.
AB  - BACKGROUND: Both impaired left ventricular (LV) global longitudinal strain (GLS)
      and increased plasma concentrations of natriuretic peptides(NP) are associated
      with a poor outcome in heart failure (HF). Increased levels of NP reflect
      increased wall stress of the LV. However, little is known about the relationship
      between LV GLS and NP. This aim of this study was to evaluate the relationship
      between the echocardiographic measure LV GLS and plasma levels of NP. METHODS: We
      prospectively included 149 patients with verified systolic HF at the baseline
      visit in an outpatient HF clinic. LV GLS was assessed by two dimension speckle
      tracking and plasma concentrations of N-terminal-pro-brain-natriuretic-peptide
      (NT-proBNP) and pro-atrial-natriuretic-peptide (proANP) were analysed. RESULTS:
      The patients had a median age of 70 years, 28.2 % were females, 26.5 % were in
      functional class III-IV, median left ventricular ejection fraction (LVEF) was 33
      % and median LV GLS was -11 %. LV GLS was associated with increased plasma
      concentrations of NT-proBNP and proANP in multivariate logistic regression (NT
      proBNP: Odds RatioGLS: 7.25, 95 %-CI: 2.48-21.1, P < 0.001 and proANP: Odds
      RatioGLS: 3.26, 95-%-CI: 1.28-8.30, P = 0.013) and linear regression (NT-proBNP:
      betaGLS: 1.19, 95 %-CI: 0.62-1.76, P < 0.001 and proANP: betaGLS: 0.42, 95-%-CI:
      0.11-0.72, P = 0.007) models after adjustment for traditional confounders (age,
      gender, body-mass-index, atrial fibrillation, renal function) and left atrial
      volume index. CONCLUSION: Impaired LV GLS is associated with increased plasma
      concentrations of NP and our data suggest that left ventricular myocardial
      mechanics estimated by LV GLS reflects myocardial wall stress in chronic systolic
      HF.

PMID- 26289431
TI  - Structural characterization of the carbohydrate-binding module of NanA sialidase,
      a pneumococcal virulence factor.
AB  - BACKGROUND: Streptococcus pneumoniae Neuraminidase A (NanA) is a multi-domain
      protein anchored to the bacterial surface. Upstream of the catalytic domain of
      NanA is a domain that conforms to the sialic acid-recognising CBM40 family of the
      CAZY (carbohydrate-active enzymes) database. This domain has been identified to
      play a critical role in allowing the bacterium to promote adhesion and invasion
      of human brain microvascular endothelial cells, and hence may play a key role in
      promoting bacterial meningitis. In addition, the CBM40 domain has also been
      reported to activate host chemokines and neutrophil recruitment during infection.
      RESULTS: Crystal structures of both apo- and holo- forms of the NanA CBM40 domain
      (residues 121 to 305), have been determined to 1.8 A resolution. The domain
      shares the fold of other CBM40 domains that are associated with sialidases. When
      in complex with alpha2,3- or alpha2,6-sialyllactose, the domain is shown to
      interact only with the terminal sialic acid. Significantly, a deep acidic pocket
      adjacent to the sialic acid-binding site is identified, which is occupied by a
      lysine from a symmetry-related molecule in the crystal. This pocket is adjacent
      to a region that is predicted to be involved in protein-protein interactions.
      CONCLUSIONS: The structural data provide the details of linkage-independent
      sialyllactose binding by NanA CBM40 and reveal striking surface features that may
      hold the key to recognition of binding partners on the host cell surface. The
      structure also suggests that small molecules or sialic acid analogues could be
      developed to fill the acidic pocket and hence provide a new therapeutic avenue
      against meningitis caused by S. pneumoniae.

PMID- 26289430
TI  - Bidirectional role of IL-6 signal in pathogenesis of lung fibrosis.
AB  - BACKGROUND: Various signals are known to participate in the pathogenesis of lung
      fibrosis. Our aim was to determine which signal is predominantly mobilized in the
      early inflammatory phase and thereafter modulates the development of lung
      fibrosis. METHODS: Mice received a single dose of 3 mg/kg body weight of
      bleomycin (BLM) and were sacrificed at designated days post-instillation (dpi).
      Lung homogenates and sections from mice in the early inflammatory phase were
      subjected to phospho-protein array analysis and immunofluorescence studies,
      respectively. Bronchoalveolar lavage fluid (BALF) from mice was subjected to an
      enzyme-linked immunosorbent assay (EIA) for interleukin (IL)-6 and evaluation of
      infiltrated cell populations. The effects of endogenous and exogenous IL-6 on the
      BLM-induced apoptotic signal in A549 cells and type 2 pneumocytes were
      elucidated. In addition, the effect of IL-6-neutralizing antibody on BLM-induced
      lung injury was evaluated. RESULTS: Phospho-protein array revealed that BLM
      induced phosphorylation of molecules downstream of the IL-6 receptor such as
      Stat3 and Akt in the lung at 3 dpi. At 3 dpi, immunofluorescence studies showed
      that signals of phospho-Stat3 and -Akt were localized in type 2 pneumocytes, and
      that BLM-induced IL-6-like immunoreactivity was predominantly observed in type 2
      pneumocytes. Activation of caspases in BLM-treated A549 cells and type 2
      pneumocytes was augmented by application of IL-6-neutralizing antibody, a PI3K
      inhibitor or a Stat3 inhibitor. EIA revealed that BLM-induced IL-6 in BALF was
      biphasic, with the first increase from 0.5 to 3 dpi followed by the second
      increase from 8 to 10 dpi. Blockade of the first increase of IL-6 by IL-6
      neutralizing antibody enhanced apoptosis of type 2 pneumocytes and neutrophilic
      infiltration and markedly accelerated fibrosis in the lung. In contrast, blockade
      of the second increase of IL-6 by IL-6-neutralizing antibody ameliorated lung
      fibrosis. CONCLUSIONS: The present study demonstrated that IL-6 could play a
      bidirectional role in the pathogenesis of lung fibrosis. In particular,
      upregulation of IL-6 at the early inflammatory stage of BLM-injured lung has
      antifibrotic activity through regulating the cell fate of type 2 pneumocytes in
      an autocrine/paracrine manner.

PMID- 26289432
TI  - Drying Methods Alter Angiotensin-I Converting Enzyme Inhibitory Activity,
      Antioxidant Properties, and Phenolic Constituents of African Mistletoe (Loranthus
      bengwensis L) Leaves.
AB  - This study investigated the most appropriate drying method (sun drying, oven
      drying, or air drying) for mistletoe leaves obtained from almond tree. The
      phenolic constituents were characterized using high-performance liquid
      chromatography-diode array detector, while the inhibitory effect of the aqueous
      extracts of the leaves on angiotensin-I converting enzyme (ACE) was determined in
      vitro as also the antioxidant properties. Oven-dried extract (kidney [276.09
      MUg/mL] and lungs [303.41 MUg/mL]) had the highest inhibitory effect on ACE,
      while air-dried mistletoe extract (kidney [304.47 MUg/mL] and lungs [438.72
      MUg/mL]) had the least. Furthermore, the extracts dose-dependently inhibited
      Fe(2+) and sodium nitroprusside-induced lipid peroxidation in rat's heart and
      kidney. Also, all extracts exhibited antioxidative properties as typified by
      their radical scavenging and Fe-chelating ability. Findings from this study
      revealed that oven drying is the best of the 3 drying methods used for mistletoe
      obtained from almond host tree, thus confirming that diversity in drying methods
      leads to variation in phenolic constituents and biological activity of plants. 

PMID- 26289434
TI  - Unfolding the band structure of non-crystalline photonic band gap materials.
AB  - Non-crystalline photonic band gap (PBG) materials have received increasing
      attention, and sizeable PBGs have been reported in quasi-crystalline structures
      and, more recently, in disordered structures. Band structure calculations for
      periodic structures produce accurate dispersion relations, which determine group
      velocities, dispersion, density of states and iso-frequency surfaces, and are
      used to predict a wide-range of optical phenomena including light propagation,
      excited-state decay rates, temporal broadening or compression of ultrashort
      pulses and complex refraction phenomena. However, band calculations for non
      periodic structures employ large super-cells of hundreds to thousands building
      blocks, and provide little useful information other than the PBG central
      frequency and width. Using stereolithography, we construct cm-scale disordered
      PBG materials and perform microwave transmission measurements, as well as finite
      difference time-domain (FDTD) simulations. The photonic dispersion relations are
      reconstructed from the measured and simulated phase data. Our results demonstrate
      the existence of sizeable PBGs in these disordered structures and provide
      detailed information of the effective band diagrams, dispersion relation, iso
      frequency contours, and their angular dependence. Slow light phenomena are also
      observed in these structures near gap frequencies. This study introduces a
      powerful tool to investigate photonic properties of non-crystalline structures
      and provides important effective dispersion information, otherwise difficult to
      obtain. 

PMID- 26289435
TI  - Drug targeting to arthritic region via folic acid appended surface-engineered
      multi-walled carbon nanotubes.
AB  - This study was aimed at developing and investigating folate anchored carbon
      nanotubes for targeting an anti-arthritic drug, Methotrexate (MTX) to
      inflammatory arthritic region. The folic acid (FA) was conjugated to amidated
      multi-walled carbon nanotubes (MWCNTs) and confirmed by Fourier transform
      infrared (FTIR), (1)H NMR spectroscopy and X-ray diffraction analysis. The MTX
      was loaded into the pristine and functionalized-MWCNTs and extensively
      characterized in vitro and in vivo studies. The drug entrapment efficiency was
      found high in folate conjugated MWCNTs. In vitro drug release in PBS (pH 7.4)
      from pristine MWCNTs and folate conjugated MWCNTs formulation was found to be
      66.35 +/- 2.3 and 56.88 +/- 1.9% in 24 h, respectively. Folate conjugated MWCNTs
      significantly increased (p < 0.005) the percentage inhibition of arthritis,
      biological half-life and volume of distribution of MTX as compared to MTX-loaded
      naked MWCNTs as well as free MTX. In in vivo biodistribution studies, MTX was
      found to be significantly higher (p < 0.005) in arthritic joints from folate
      functionalized MWCNTs as compared to free drug as well as drug-loaded naked
      MWCNTs. The present outcomes highlights the propensity of drug-loaded
      functionalized MWCNTs to alter the pharmacokinetics as well as sustained and
      targeted drug delivery system as well. 

PMID- 26289433
TI  - Losing dexterity: patterns of impaired coordination of finger movements in
      musician's dystonia.
AB  - Extensive training can bring about highly-skilled action, but may also impair
      motor dexterity by producing involuntary movements and muscular cramping, as seen
      in focal dystonia (FD) and tremor. To elucidate the underlying neuroplastic
      mechanisms of FD, the present study addressed the organization of finger
      movements during piano performance in pianists suffering from the condition.
      Principal component (PC) analysis identified three patterns of fundamental joint
      coordination constituting finger movements in both patients and controls. The
      first two coordination patterns described less individuated movements between the
      "dystonic" finger and key-striking fingers for patients compared to controls. The
      third coordination pattern, representing the individuation of movements between
      the middle and ring fingers, was evident during a sequence of strikes with these
      fingers in controls, which was absent in the patients. Consequently, rhythmic
      variability of keystrokes was more pronounced during this sequence of strikes for
      the patients. A stepwise multiple-regression analysis further identified greater
      variability of keystrokes for individuals displaying less individuated movements
      between the affected and striking fingers. The findings suggest that FD alters
      dexterous joint coordination so as to lower independent control of finger
      movements, and thereby degrades fine motor control. 

PMID- 26289436
TI  - Effects of intraduodenal infusion of the branched-chain amino acid leucine on ad
      libitum eating, gut motor and hormone functions, and glycemia in healthy men.
AB  - BACKGROUND: Branched-chain amino acids (BCAAs), particularly leucine, act as
      nutrient signals regulating protein synthesis and degradation as well as glucose
      metabolism. In addition, leucine has been demonstrated in animal experiments to
      modulate eating and energy homeostasis. OBJECTIVE: We aimed to characterize the
      effects of physiologic and supraphysiologic loads of intraduodenal leucine on
      eating, gut hormone and motor functions, and blood glucose in humans. DESIGN:
      Twelve lean men were studied on 3 occasions in a randomized, double-blind order.
      Antropyloroduodenal motility, plasma ghrelin, cholecystokinin, glucagon-like
      peptide 1, peptide YY, insulin, glucagon, blood glucose, appetite perceptions,
      and gastrointestinal symptoms were measured during 90-min intraduodenal infusions
      of leucine at 0.15 kcal/min (total 3.3 g, 13.5 kcal), 0.45 kcal/min (total 9.9 g,
      40.5 kcal), or saline (control). Ad libitum eating from a buffet lunch was
      quantified immediately after the infusions. RESULTS: Leucine at 0.45 kcal/min
      inhibited eating (energy intake by ~13%, P < 0.05), increased plasma
      cholecystokinin, slightly reduced blood glucose and increased plasma insulin, and
      decreased antral pressures (all P < 0.05). Leucine at 0.15 kcal/min had no effect
      on food intake, blood glucose, or antral pressures but also slightly increased
      plasma cholecystokinin (P < 0.05). Neither dose affected plasma ghrelin,
      glucagon, glucagon-like peptide 1 and peptide YY, or pyloric and duodenal
      pressures. Plasma leucine concentrations were related to the dose of
      intraduodenal leucine, with substantial increases during both 0.15 and 0.45
      kcal/min. CONCLUSIONS: The effects of intraduodenal infusions of free leucine on
      eating are probably not primarily mediated by changes in gut motor and hormone
      functions, with perhaps the exception of cholecystokinin. Instead, increased
      plasma leucine concentrations may be a potential signal mediating the eating
      inhibitory effect of leucine. The study was registered as a clinical trial with
      the Australia and New Zealand Clinical Trial Registry (www.anzctr.org.au) as
      ACTRN12613000899741.

PMID- 26289437
TI  - Intraduodenal infusion of a combination of tastants decreases food intake in
      humans.
AB  - BACKGROUND: Taste receptors are expressed not only in taste buds but also in the
      gastrointestinal tract. It has been hypothesized that these receptors may play a
      role in satiety and food intake. OBJECTIVE: This study investigated the effect of
      intraduodenal tastant infusions (bitter, sweet, and umami) on food intake, hunger
      and fullness, gastrointestinal symptoms, and gastrointestinal peptide release.
      DESIGN: Fifteen healthy volunteers [6 male; mean +/- SEM age: 23.9 +/- 2.0 y;
      mean +/- SEM body mass index (in kg/m(2)): 22.4 +/- 0.3] received 5 treatments in
      a double-blind, randomized, placebo-controlled crossover design. Test days
      started with the insertion of a nasoduodenal catheter followed by a standardized
      liquid breakfast. Participants received an intraduodenal infusion 150 min after
      breakfast, containing quinine (bitter), rebaudioside A (sweet), monosodium
      glutamate (umami), a combination of the 3 tastants, or placebo (tap water) over a
      period of 60 min. Food intake was measured during an ad libitum meal, and visual
      analog scales were used to monitor gastrointestinal complaints and hunger and
      fullness scores. Blood samples were drawn at regular intervals for
      cholecystokinin, glucagon-like peptide 1 (GLP-1), and peptide YY (PYY) analysis.
      RESULTS: Infusion of the combination of tastants substantially decreased food
      intake (422 +/- 97 compared with 486 +/- 104 kcal for placebo, P < 0.05), whereas
      both a combination of tastants and umami decreased hunger scores compared with
      placebo. No change in cholecystokinin, GLP-1, or PYY concentrations was observed
      during the infusions. Intraduodenal infusions of the tastants did not result in
      gastrointestinal symptoms. CONCLUSIONS: Intraduodenal infusion of umami and a
      combination of tastants inhibits feelings of hunger, but only the latter also
      reduces food intake. However, these alterations were not accompanied by changes
      in the plasma concentrations of the gut-derived peptides cholecystokinin, GLP-1,
      or PYY. This trial was registered at clinicaltrials.gov as NCT01956838.

PMID- 26289438
TI  - Alcohol intake, reproductive hormones, and menstrual cycle function: a
      prospective cohort study.
AB  - BACKGROUND: Although habitual low-to-moderate alcohol intake has been linked with
      reduced all-cause mortality and morbidity, the effect of recent alcohol intake on
      female reproductive function has not been clearly established. OBJECTIVE: We
      assessed the relation between acute alcohol consumption, reproductive hormones,
      and markers of menstrual cycle dysfunction including sporadic anovulation,
      irregular cycle length, luteal phase deficiency, long menses, and heavy blood
      loss. DESIGN: A total of 259 healthy, premenopausal women from Western New York
      were followed for <=2 menstrual cycles (2005-2007) and provided fasting blood
      specimens during <=8 visits/cycle and four 24-h dietary recalls/cycle. Linear
      mixed models were used to estimate associations between previous day's alcohol
      intake and hormone concentrations, whereas Poisson regression was used to assess
      RR of cycle-average alcohol intake and menstrual cycle function. RESULTS: For
      every alcoholic drink consumed, the geometric mean total and free estradiol,
      total and free testosterone, and luteinizing hormone were higher by 5.26% (95%
      CI: 1.27%, 9.41%), 5.82% (95% CI: 1.81%, 9.99%), 1.56% (95% CI: 0.23%, 2.90%),
      1.42% (95% CI: 0.02%, 2.84%), and 6.18% (95% CI: 2.02%, 10.52%), respectively,
      after adjustment for age, race, percentage of body fat, perceived stress, pain
      medication use, sexual activity, caffeine, and sleep. Binge compared with
      nonbinge drinking (defined as reporting >=4 compared with <4 drinks/d,
      respectively) was associated with 64.35% (95% CI: 18.09%, 128.71%) and 63.53%
      (95% CI: 17.41%, 127.73%) higher total and free estradiol. No statistically
      significant associations were shown between cycle-average alcohol intake and
      menstrual cycle function. CONCLUSION: Although recent moderate alcohol intake
      does not appear to have adverse short-term effects on menstrual cycle function,
      including sporadic anovulation, potential protective and deleterious long-term
      effects of alterations in reproductive hormones on other chronic diseases warrant
      additional investigation.

PMID- 26289440
TI  - Presence of cleaner wrasse increases the recruitment of damselfishes to coral
      reefs.
AB  - Mutualisms affect the biodiversity, distribution and abundance of biological
      communities. However, ecological processes that drive mutualism-related shifts in
      population structure are often unclear and must be examined to elucidate how
      complex, multi-species mutualistic networks are formed and structured. In this
      study, we investigated how the presence of key marine mutualistic partners can
      drive the organisation of local communities on coral reefs. The cleaner wrasse,
      Labroides dimidiatus, removes ectoparasites and reduces stress hormones for
      multiple reef fish species, and their presence on coral reefs increases fish
      abundance and diversity. Such changes in population structure could be driven by
      increased recruitment of larval fish at settlement, or by post-settlement
      processes such as modified levels of migration or predation. We conducted a
      controlled field experiment to examine the effect of cleaners on recruitment
      processes of a common group of reef fishes, and showed that small patch reefs (61
      285 m(2)) with cleaner wrasse had higher abundances of damselfish recruits than
      reefs from which cleaner wrasse had been removed over a 12-year period. However,
      the presence of cleaner wrasse did not affect species diversity of damselfish
      recruits. Our study provides evidence of the ecological processes that underpin
      changes in local population structure in the presence of a key mutualistic
      partner. 

PMID- 26289439
TI  - Functional measures, inflammatory markers and endothelin-1 as predictors of 360
      day survival in centenarians.
AB  - Centenarians represent a rapidly growing population. To better characterize this
      specific age group, we have performed a cross-sectional study to observe
      associations between functional measures and a range of biochemical markers,
      including inflammatory markers and their significance as predictors of 360-day
      survival. Medical history and physical and functional assessment (Mini-Mental
      State Examination (MMSE), Katz Index (activities of daily living, ADL) and
      Barthel Index (Barthel Index) of Activities of Daily Living, and Lawton
      Instrumental Activities of Daily Living Scale (Lawton IADL)) were conducted on 86
      101.9 +/- 1.2-year-old (mean +/- SD) subjects (70 women, 16 men). Blood tests
      were performed on 84 subjects of whom 43 also had extended biomarker assessment.
      As a reference group 30 51.8 +/- 5.0-year old healthy subjects (20 women, 10 men)
      were recruited. The centenarians received follow-up phone calls. Fifty-two
      centenarians (60 %) survived >=360 days. Longer survival was associated with
      higher MMSE (hazard ratio, HR = 0.934, 95 % confidence interval (CI) 0.896-0.975,
      P = .002), ADL (HR = 0.840, 95 % CI 0.716-0.985, P = .032), Barthel Index (HR =
      0.988, 95 % CI 0.977-0.999, P = .026), and albumin level (HR .926, 95 % CI 0.870
      0.986, P .016) and with lower white blood cell (WBC) (HR = 1.161, 95 % CI 1.059
      1.273, P = .001), C-reactive protein (CRP) (HR = 1.032, 95 % CI 1.014-1.050, P <
      .001), IL-6 (HR = 1.182, 95 % CI 1.047-1.335, P = .007), and endothelin-1 (ET-1)
      level (HR = 3.711, 95 % CI 1.233-11.169, P = .020). Centenarians had higher 360
      day survival probability with MMSE >=13 (P < .001), ADL >=1 (P < .001), Barthel
      Index >=15 (P < .001), Lawton IADL >=10 points (P = .009), WBC <8.3 G/L (P =
      .039), CRP <10 mg/L (P < .001), IL-6 <6 pg/mL (P .002), and ET-1 <1.1 pg/mL (P
      .007). Our results indicate that functional measures, inflammatory markers, and
      endothelin-1 are predictors of 360-day survival in centenarians.

PMID- 26289441
TI  - Sex-specific maternal effects in a viviparous fish.
AB  - Mothers vary in their effects on their offspring, but studies of variation in
      maternal effects rarely ask whether differences between mothers are consistent
      for sons and daughters. Here, we analysed maternal effects in the mosquitofish
      Gambusia holbrooki for development time and adult size of sons and daughters, and
      a primary male sexual character (gonopodium length). We found substantial
      maternal effects on all traits, most notably for gonopodium length. There were
      significant correlations within each sex for maternal effects on different
      traits, indicative of trade-offs between development rate and adult size. By
      contrast, there was no evidence of any consistency in maternal effects on sons
      and daughters. This suggests that the evolution of maternal effects will follow
      independent trajectories dependent on sex-specific selection on offspring.
      Importantly, failure to recognize the sex-specific nature of maternal effects in
      this population would have substantially underestimated the extent of their
      variation between mothers. 

PMID- 26289442
TI  - All the better to see you with: eyes and claws reveal the evolution of divergent
      ecological roles in giant pterygotid eurypterids.
AB  - Pterygotid eurypterids have traditionally been interpreted as active, high-level,
      visual predators; however, recent studies of the visual system and cheliceral
      morphology of the pterygotid Acutiramus contradict this interpretation. Here, we
      report similar analyses of the pterygotids Erettopterus, Jaekelopterus and
      Pterygotus, and the pterygotid sister taxon Slimonia. Representative species of
      all these genera have more acute vision than A. cummingsi. The visual systems of
      Jaekelopterus rhenaniae and Pterygotus anglicus are comparable to that of modern
      predatory arthropods. All species of Jaekelopterus and Pterygotus have robust
      crushing chelicerae, morphologically distinct from the weaker slicing chelicerae
      of Acutiramus. Vision in Erettopterus osiliensis and Slimonia acuminata is more
      acute than in Acutiramus cummingsi, but not to the same degree as in modern
      active predators, and the morphology of the chelicerae in these genera suggests a
      grasping function. The pterygotids evolved with a shift in ecology from
      generalized feeder to specialized predator. Pterygotid eurypterids share a
      characteristic morphology but, although some were top predators, their ecology
      differs radically between genera. 

PMID- 26289444
TI  - Doped Si nanoparticles with conformal carbon coating and cyclized
      polyacrylonitrile network as high-capacity and high-rate lithium-ion battery
      anodes.
AB  - Doped Si nanoparticles (SiNPs) with conformal carbon coating and cyclized
      polyacrylonitrile (PAN) network displayed capacities of 3500 and 3000 mAh g(-1)
      at C/20 and C/10, respectively. At 1 C, the electrode preserves a specific
      discharge capacity of ~1500 mAh g(-1) for at least 60 cycles without decay. Al2O3
      atomic layer deposition (ALD) helps improve the initial Coulombic efficiency (CE)
      to 85%. The dual coating of conformal carbon and cyclized-PAN help alleviate
      volume change and facilitate charge transfer. Ultra-thin Al2O3 ALD layers help
      form a stable solid electrolyte interphase interface. 

PMID- 26289443
TI  - Evidence supporting a role for SMAD2/3 in bovine early embryonic development:
      potential implications for embryotropic actions of follistatin.
AB  - The TGF-beta-SMAD signaling pathway is involved in regulation of various aspects
      of female reproduction. However, the intrinsic functional role of SMADs in early
      embryogenesis remains poorly understood. Previously, we demonstrated that
      treatment with follistatin, an activin (TGF-beta superfamily ligand)-binding
      protein, is beneficial for bovine early embryogenesis and specific embryotropic
      actions of follistatin are dependent on SMAD4. Because SMAD4 is a common SMAD
      that can bind both SMAD2/3 and SMAD1/5, the objective of this study was to
      further determine the intrinsic role of SMAD2/3 in the control of early
      embryogenesis and delineate if embryotropic actions of follistatin in early
      embryos are SMAD2/3 dependent. By using a combination of pharmacological and
      small interfering RNA-mediated inhibition of SMAD2/3 signaling in the presence or
      absence of follistatin treatment, our results indicate that SMAD2 and SMAD3 are
      both required for bovine early embryonic development and stimulatory actions of
      follistatin on 8- to 16-cell and that blastocyst rates, but not early cleavage,
      are muted when SMAD2/3 signaling is inhibited. SMAD2 deficiency also results in
      reduced expression of the bovine trophectoderm cell-specific gene CTGF. In
      conclusion, the present work provides evidence supporting a functional role of
      SMAD2/3 in bovine early embryogenesis and that specific stimulatory actions of
      follistatin are not observed in the absence of SMAD2/3 signaling. 

PMID- 26289445
TI  - Roseomonas wooponensis sp. nov., isolated from wetland freshwater.
AB  - A non-motile, cocobacilli-shaped and pink-pigmented bacterium, designated strain
      WW53T, was isolated from wetland freshwater (Woopo wetland, Republic of Korea).
      Cells were Gram-stain-negative, catalase- and oxidase-positive. The major fatty
      acids were C18 : 1omega7c/C18 : 1omega6c and C16 : 0.The predominant quinone and
      polyamine were ubiquinone 10 (Q-10) and spermidine, respectively. The DNA G+C
      content was 71 mol%. The major polar lipids were phosphatidylethanolamine,
      phosphatidylcholine and an unknown aminolipid. Phylogenetic analysis based on 16S
      rRNA gene sequences indicated that strain WW53T belongs to the family
      Acetobacteraceae, and is related to the genus Roseomonas. Strain WW53T was most
      closely related to Roseomonas stagni HS-69T (95.3 % 16S rRNA gene sequence
      similarity). Results of a polyphasic taxonomy study suggested that the isolate
      represents a novel species in the genus Roseomonas, for which the name Roseomonas
      wooponensis sp. nov. is proposed. The type strain is WW53T ( = KCTC 32534T = JCM
      19527T).

PMID- 26289447
TI  - 24-h sheltering behaviour of individually kept horses during Swedish summer
      weather.
AB  - BACKGROUND: Provision of shelter for horses kept on summer pasture is rarely
      considered in welfare guidelines, perhaps because the benefits of shelter in warm
      conditions are poorly documented scientifically. For cattle, shade is a valued
      resource during summer and can mitigate the adverse effects of warm weather on
      well-being and performance. We found in a previous study that horses utilized
      shelters frequently in summer. A shelter with a roof and closed on three sides
      (shelter A) was preferred and can reduce insect pressure whereas a shelter with
      roof and open on three sides was not utilized. However, shelter A restricts the
      all-round view of a horse, which may be important for horses as flight animals.
      Therefore, we studied whether a shelter with roof, where only the upper half of
      the rear wall was closed (shelter B), would be utilized while maintaining insect
      protection properties and satisfying the horses' sense for security. A third
      shelter was offered with walls but no roof (shelter C) to evaluate whether the
      roof itself is an important feature from the horse's perspective. Eight Warmblood
      horses were tested each for 2 days, kept individually for 24 h in two paddocks
      with access to shelters A and B, or shelters A and C, respectively. Shelter use
      was recorded continuously during the night (1800-2400 h, 0200-0600 h) and the
      following day (0900-1600 h), and insect defensive behaviour (e.g., tail swish) in
      instantaneous scan samples at 5-min intervals during daytime. RESULTS: Seven
      horses used both shelters A and B, but when given the choice between shelters A
      and C, shelter C was scarcely visited. There was no difference in duration of
      shelter use between night (105.8 +/- 53.6 min) and day (100.8 +/- 53.8, P =
      0.829). Daytime shelter use had a significant effect on insect defensive
      behaviours (P = 0.027). The probability of performing these behaviours was lowest
      when horses used shelter A compared to being outside (P = 0.038). CONCLUSIONS:
      Horses only utilized shelters with a roof whilst a shelter with roof and closed
      on three sides had the best potential to lower insect disturbance during daytime
      in summer.

PMID- 26289446
TI  - Roles of transcriptional factor 7 in production of inflammatory factors for lung
      diseases.
AB  - Lung disease is the major cause of death and hospitalization worldwide.
      Transcription factors such as transcription factor 7 (TCF7) are involved in the
      pathogenesis of lung diseases. TCF7 is important for T cell development and
      differentiation, embryonic development, or tumorogenesis. Multiple TCF7 isoforms
      can be characterized by the full-length isoform (FL-TCF7) as a transcription
      activator, or dominant negative isoform (dn-TCF7) as a transcription repressor.
      TCF7 interacts with multiple proteins or target genes and participates in several
      signal pathways critical for lung diseases. TCF7 is involved in pulmonary
      infection, allergy or asthma through promoting T cells differentiating to Th2 or
      memory T cells. TCF7 also works in tissue repair and remodeling after acute lung
      injury. The dual roles of TCF7 in lung cancers were discussed and it is
      associated with the cellular proliferation, invasion or metastasis. Thus, TCF7
      plays critical roles in lung diseases and should be considered as a new
      therapeutic target. 

PMID- 26289448
TI  - Effects of telephone-delivered lifestyle support on the development of diabetes
      in participants at high risk of type 2 diabetes: J-DOIT1, a pragmatic cluster
      randomised trial.
AB  - OBJECTIVES: To examine the effects of telephone-delivered lifestyle coaching on
      preventing the development of type 2 diabetes mellitus (T2DM) in participants
      with impaired fasting glucose (IFG). DESIGN: Cluster randomised trial. SETTING:
      40 groups from 17 healthcare divisions in Japan: companies (31), communities (6)
      and mixed settings (3). PARTICIPANTS: Participants aged 20-65 years with fasting
      plasma glucose (FPG) of 5.6-6.9 mmol/L were invited from the 17 healthcare
      divisions. RANDOMISATION: The groups were then randomly assigned to an
      intervention or a control arm by independent statisticians according to a
      computer-generated list. INTERVENTION: The intervention arm received a 1-year
      telephone-delivered intervention provided by three private lifestyle support
      centres (at different frequencies: low-frequency (3 times), middle-frequency (6
      times) and high-frequency (10 times) support calls). The intervention and control
      arms both received self-help devices such as a weight scale and pedometer.
      OUTCOMES: Participants were followed up using data from annual health check-ups
      and a questionnaire regarding lifestyle. The primary outcome was the development
      of T2DM defined as FPG >= 7.0 mmol/L, the diagnosis of diabetes, or use of an
      antidiabetic drug, confirmed by referring to medical cards. RESULTS: Of 14,473
      screened individuals, participants were enrolled in either the intervention (n =
      1240) arm or control (n = 1367) arm. Overall, the HR for the development of T2DM
      in the intervention arm during 5.5 years was 1.00 (95% CI 0.74 to 1.34). In the
      subanalysis, the HR was 0.59 (95% CI 0.42 to 0.83) in the subgroup that received
      phone calls the most frequently, compared with the control arm. A limitation of
      the study includes a lack of blinding. CONCLUSIONS: High-frequency telephone
      delivered lifestyle support could effectively prevent T2DM in participants with
      IFG in a primary healthcare setting, although low-frequency and middle-frequency
      phone calls did not. TRIAL REGISTRATION NUMBER: This trial has been registered
      with the University Hospital Medical Information Network (UMIN000000662).

PMID- 26289449
TI  - Perceived current needs, psychological distress and functional impairment in a
      war-affected setting: a cross-sectional study in South Sudan.
AB  - OBJECTIVES: To examine the current perceived needs of the general population in a
      war-affected setting, and to study the influence of perceived needs on the
      participants' mental health status and functional impairment across genders.
      METHODS: A cross-sectional community survey (n=464) was conducted in war-affected
      South Sudan. Three regression models were analysed. Perceived needs were assessed
      with the Humanitarian Emergency Settings Perceived Needs Scale. Psychological
      distress was measured with the General Health Questionnaire and level of
      functioning by the Short Form Health Survey (SF-12). RESULTS: The most frequently
      expressed needs were related to drinking water, alcohol and drug use in the
      community and access to sanitation facilities. No gender differences were found
      regarding the level of perceived needs or the number of traumatic events. Higher
      level of perceived needs significantly predicted psychological distress and lower
      level of functioning even when numbers of experienced trauma events were taken
      into account. CONCLUSIONS: The associations of higher level of needs and trauma
      experiences, on the one hand, and negative health outcomes on the other,
      necessitate a greater integration of interventions directed towards the
      population's perceived needs and mental health, particularly for those who have
      been exposed to trauma.

PMID- 26289450
TI  - Development of an algorithm to provide awareness in choosing study designs for
      inclusion in systematic reviews of healthcare interventions: a method study.
AB  - OBJECTIVES: To develop an algorithm that aims to provide guidance and awareness
      for choosing multiple study designs in systematic reviews of healthcare
      interventions. DESIGN: Method study: (1) To summarise the literature base on the
      topic. (2) To apply the integration of various study types in systematic reviews.
      (3) To devise decision points and outline a pragmatic decision tree. (4) To check
      the plausibility of the algorithm by backtracking its pathways in four systematic
      reviews. RESULTS: (1) The results of our systematic review of the published
      literature have already been published. (2) We recaptured the experience from our
      four previously conducted systematic reviews that required the integration of
      various study types. (3) We chose length of follow-up (long, short), frequency of
      events (rare, frequent) and types of outcome as decision points (death, disease,
      discomfort, disability, dissatisfaction) and aligned the study design labels
      according to the Cochrane Handbook. We also considered practical or ethical
      concerns, and the problem of unavailable high-quality evidence. While applying
      the algorithm, disease-specific circumstances and aims of interventions should be
      considered. (4) We confirmed the plausibility of the pathways of the algorithm.
      CONCLUSIONS: We propose that the algorithm can assist to bring seminal features
      of a systematic review with multiple study designs to the attention of anyone who
      is planning to conduct a systematic review. It aims to increase awareness and we
      think that it may reduce the time burden on review authors and may contribute to
      the production of a higher quality review.

PMID- 26289451
TI  - Regional health expenditure and health outcomes after out-of-hospital cardiac
      arrest in Japan: an observational study.
AB  - OBJECTIVES: Japan is considering policies to set the target health expenditure
      level for each region, a policy approach that has been considered in many other
      countries. The objective of this study was to examine the relationship between
      regional health expenditure and health outcomes after out-of-hospital cardiac
      arrest (OHCA), which incorporates the qualities of prehospital, in-hospital and
      posthospital care systems. DESIGN: We examined the association between prefecture
      level per capita health expenditure and patients' health outcomes after OHCA.
      SETTING: We used a nationwide, population-based registry system of OHCAs that
      captured all cases with OHCA resuscitated by emergency responders in Japan from
      2005 to 2011. PARTICIPANTS: All patients with OHCA aged 1-100 years were
      analysed. OUTCOME MEASURES: The patients' 1-month survival rate, and favourable
      neurological outcome (defined as cerebral performance category 1-2) at 1-month.
      RESULTS: Among 618,154 cases with OHCA, the risk-adjusted 1-month survival rate
      varied from 3.3% (95% CI 2.9% to 3.7%) to 8.4% (95% CI 7.7% to 9.1%) across
      prefectures. The risk-adjusted probabilities of favourable neurological outcome
      ranged from 1.6% (95% CI 1.4% to 1.9%) to 3.7% (95% CI 3.4% to 3.9%). Compared
      with prefectures with lowest tertile health expenditure, 1-month survival rate
      was significantly higher in medium-spending (adjusted OR 1.31, 95% CI 1.03 to
      1.66, p=0.03) and high-spending prefectures (adjusted OR 1.30, 95% CI 1.03 to
      1.64, p=0.02), after adjusting for patient characteristics. There was no
      difference in the survival between medium-spending and high-spending regions. We
      observed similar patterns for favourable neurological outcome. Additional
      adjustment for regional per capita income did not affect our overall findings.
      CONCLUSIONS: We observed a wide variation in the health outcomes after OHCA
      across regions. Low-spending regions had significantly worse health outcomes
      compared with medium-spending or high-spending regions, but no difference was
      observed between medium-spending and high-spending regions. Our findings suggest
      that focusing on the median spending may be the optimum that allows for saving
      money without compromising patient outcomes.

PMID- 26289453
TI  - Nature of Rutile Nuclei in Anatase-to-Rutile Phase Transition.
AB  - The solid phase transition of TiO2, in particular anatase to rutile, has been
      extensively studied in the past 30 years. To seek the nucleation site at the
      beginning of phase transition is highly challenging, which asks for new
      theoretical techniques with high spatial and temporal resolution. This work
      reports the first evidence on the atomic structure of the nucleation sites in the
      TiO2 anatase-to-rutile phase transition. Novel automated theoretical methods,
      namely stochastic surface walking based pathway sampling methods, are utilized to
      resolve the lowest energy pathways at the initial stage of phase transition. We
      show that among common anatase surfaces, only the (112) ridged surface provides
      the nucleation site for phase transition, which can lead to the formation of both
      TiO2-II and brookite thin slabs. The TiO2-II phase is kinetically preferred
      product; the propagation into the subsurface is still hindered by high barriers
      that is the origin for the slow kinetics of nuclei formation. The rutile nuclei
      are thus not rutile phase but nascent metastable TiO2-II phase in an anatase
      matrix. The phase transition kinetics is found to be sensitive to the compressive
      strain and the crystallographic directions. The results rationalize the size and
      morphology dependence of the anisotropic phase transition kinetics of anatase
      particles and could facilitate the rational design of material via controlled
      solid phase transition. 

PMID- 26289452
TI  - The impact of road traffic injury in North India: a mixed-methods study protocol.
AB  - BACKGROUND: Road traffic injuries are a large and growing public health burden,
      especially in low and middle income countries where 90% of the world's deaths due
      to road traffic injuries are estimated to occur. India is one of the fastest
      growing economies, with rapid motorisation and increasing road traffic burden.
      However, there are limited data addressing the problem of non-fatal road traffic
      injuries, with existing data being of poor quality, non-representative and
      difficult to access, and encompassing a limited number of relevant variables.
      This study aims to determine the outcomes of road traffic injuries on function
      and health-related quality of life, to assess their social impact and to weigh
      the economic cost of road traffic crashes in an urban setting in India. METHODS
      AND ANALYSIS: This prospective observational study will recruit approximately
      1500 participants injured in road traffic crashes, who are admitted to hospital
      for >24 h at any of three participating hospitals in Chandigarh, India. Face-to
      face baseline interviews will be conducted by telephone at 1, 2, 4 and 12 months
      postinjury. Standardised tools will be used to collect data on health and social
      outcomes, and on the economic impact of road traffic crashes. Descriptive
      analysis and multivariate models will be used to report outcome data and
      associations. The qualitative in-depth interviews will be analysed thematically
      using content analysis. This study will provide the first comprehensive estimates
      on outcomes of serious road traffic injury in India, including economic and
      social costs, and the impact on individuals and families. ETHICS AND
      DISSEMINATION: Primary ethics approval was received from the Postgraduate
      Institute for Medical Education and Research, institute's ethics committee,
      Chandigarh, India. Results will be disseminated via the usual scientific forums
      including peer-reviewed publications and presentations at international
      conferences.

PMID- 26289454
TI  - One Size Doesn't Fit All: Dating Abuse Against Women From the Perspective of
      South Asian Muslim Youth in Canada.
AB  - Despite the growing recognition of intersectionality in the field of domestic
      abuse, scholarship on dating abuse is still limited by its lack of attention to
      cultural context. To begin to address this gap, this article presents findings
      from an exploratory qualitative study of 11 South Asian Muslims' perceptions of
      behaviors/actions in dating relationships that they identify as being potentially
      experienced and/or understood differently by South Asian Muslim women. In
      particular, the participants identify (a) exposure to parents/community, (b)
      behaviors of a sexual nature, (c) controlling behaviors, and (d) psychological,
      emotional, and/or verbal behaviors/abuse as being experienced and understood in
      unique ways by South Asian Muslim women. By connecting these perceptions to the
      cultural context of South Asian Muslims, these findings support an
      intersectionality perspective by suggesting sociocultural variations in the
      meanings assigned to behaviors and/or actions.

PMID- 26289455
TI  - Psychometric Properties of the Cyberbullying Test, a Screening Instrument to
      Measure Cybervictimization, Cyberaggression, and Cyberobservation.
AB  - The purpose of the study was to analyze the psychometric properties of the
      Cyberbullying Test. The sample included 3,026 participants from the Basque
      Country (northern Spain), aged 12 to 18 years. Results confirmed high internal
      consistency and moderate temporal stability. Exploratory factor analysis yielded
      three moderately correlated factors (cyberobserver, cyberaggressor, and
      cybervictim). Confirmatory factor analysis ratified adequate model fit of the
      three factors. Convergent and discriminant validity were confirmed: (a)
      cybervictims use a variety of conflict resolution strategies, scoring high in
      neuroticism, openness, antisocial behavior, emotional attention, school-academic
      problems, shyness-withdrawal, psychopathological disorders, anxiety, and
      psychosomatic complaints, and low in agreeableness, responsibility, self-esteem,
      and social adjustment and (b) cyberaggressors use many aggressive conflict
      resolution strategies, scoring high in neuroticism, antisocial behavior, school
      academic problems, psychopathological and psychosomatic disorders, and low in
      empathy, agreeableness, responsibility, emotion regulation, and social
      adjustment. The study confirms the test's reliability and validity.

PMID- 26289456
TI  - Exposure to Violence of Secondary School Children with Visual Impairment.
AB  - Although violence is a serious issue that children face all over the world, there
      is little known about the extent of the violence children with disabilities
      experience. This study was conducted to identify the frequency of exposure to
      violence that students with visual impairment experience in any environment,
      directly or as a witness, and the factors associated with this exposure. The
      study was conducted as descriptive research at a Secondary School for the
      Visually Impaired in 2011-2012 with 84 individuals. A questionnaire on
      demographics, a Violence Exposure Scale, and face-to-face interviews were used as
      data collection tools. It was found that the large majority of the children with
      visual impairment in the study had encountered violence on one occasion or more,
      recently or in the past. The number of students recently exposed to violence was
      higher than the number of children encountering violence in the past. The mean
      scores of the students who had recently experienced violence were higher than the
      scores for exposure to violence in the past. A large majority of the students
      with visual impairment in the study, all of the boarding students, and most of
      the day students had been exposed to violence once or more both recently and in
      the past. It was found that being male, having a congenital visual impairment,
      and living as a boarding student were risk factors in terms of violence. It may
      be recommended that school nurses more closely monitor this group of students for
      signs of violence.

PMID- 26289457
TI  - Feminist Identity Styles, Sexual and Non-Sexual Traumatic Events, and
      Psychological Well-Being in a Sample of Polish Women.
AB  - The aim of the study was to investigate the relations between the development of
      a feminist identity and effects of traumatic stress in a sample of Polish women.
      The distinction between non-sexual and sexual traumatic events was made. It was
      hypothesized that individuals scoring high on the Synthesis and Active Commitment
      scales of the Feminist Identity Development Model would present a higher self
      esteem and lower level of depression as compared with individuals having low
      scores on those scales and high scores on the Passive Acceptance scale. It was
      also assumed that the relation between the feminist identity styles and self
      esteem and depression would be stronger in women who had experienced sexual
      traumatic events as compared with those who had experienced other kinds of
      trauma. A total of 273 women participated in the questionnaire research.
      Regression analyses were performed to test the interaction model, and the
      obtained results support all of the hypotheses.

PMID- 26289458
TI  - Childhood Physical Maltreatment and Young Adult Dating Violence: A Propensity
      Matching Approach.
AB  - Intimate partner violence disproportionately occurs among young adults and
      relates to a range of health and behavioral problems throughout the life course.
      Although numerous studies substantiate the prevailing cycle of violence
      perspective, methodological limitations in prior research prohibit the conclusion
      of a causal relationship between childhood physical maltreatment and dating
      violence perpetration and victimization in young adulthood. The current research
      applies a quasi-experimental propensity score matching approach to a large sample
      of young adults ( n = 4,168) to isolate the causal effect of childhood physical
      maltreatment on dating violence perpetration and victimization. Results suggest
      selection bias accounts for the correlation between childhood physical
      maltreatment and young adult physical dating violence perpetration and
      victimization, indicating a spurious relationship-before matching: odds ratio
      (OR) = 1.38, p < .001; OR = 1.35, p < .001; after matching: OR = 1.08; p = .379;
      OR = 1.09; p = .297. Study limitations and implications are discussed.

PMID- 26289459
TI  - Deregulation of histone-modifying enzymes and chromatin structure modifiers
      contributes to glioma development.
AB  - The epigenetic landscape is deregulated in cancer due to aberrant activation or
      inactivation of enzymes maintaining and modifying the epigenome. Histone
      modifications and global aberrations at the histone level may result in distorted
      patterns of gene expression, and malfunction of proteins that regulate chromatin
      modification and remodeling. Recent whole genome studies demonstrated that
      histones and chaperone proteins harbor mutations that may result in gross
      alterations of the epigenome leading to genome instability. Glioma development is
      a multistep process, involving genetic and epigenetic alterations. This review
      summarizes newly identified mechanisms affecting expression/functions of histone
      modifying enzymes and chromatin modifiers in gliomas. We discuss recent
      approaches to overcome epigenetic alterations with histone-modifying enzyme
      inhibitors and their prospects for glioma therapy. 

PMID- 26289460
TI  - Proximal arm kinematics affect grip force-load force coordination.
AB  - During object manipulation, grip force is coordinated with load force, which is
      primarily determined by object kinematics. Proximal arm kinematics may affect
      grip force control, as proximal segment motion could affect control of distal
      hand muscles via biomechanical and/or neural pathways. The aim of this study was
      to investigate the impact of proximal kinematics on grip force modulation during
      object manipulation. Fifteen subjects performed three vertical lifting tasks that
      involved distinct proximal kinematics (elbow/shoulder), but resulted in similar
      end-point (hand) trajectories. While temporal coordination of grip and load
      forces remained similar across the tasks, proximal kinematics significantly
      affected the grip force-to-load force ratio (P = 0.042), intrinsic finger muscle
      activation (P = 0.045), and flexor-extensor ratio (P < 0.001). Biomechanical
      coupling between extrinsic hand muscles and the elbow joint cannot fully explain
      the observed changes, as task-related changes in intrinsic hand muscle activation
      were greater than in extrinsic hand muscles. Rather, between-task variation in
      grip force (highest during task 3) appears to contrast to that in shoulder joint
      velocity/acceleration (lowest during task 3). These results suggest that complex
      neural coupling between the distal and proximal upper extremity musculature may
      affect grip force control during movements, also indicated by task-related
      changes in intermuscular coherence of muscle pairs, including intrinsic finger
      muscles. Furthermore, examination of the fingertip force showed that the human
      motor system may attempt to reduce variability in task-relevant motor output
      (grip force-to-load force ratio), while allowing larger fluctuations in output
      less relevant to task goal (shear force-to-grip force ratio). 

PMID- 26289461
TI  - Bimodal stimulus timing-dependent plasticity in primary auditory cortex is
      altered after noise exposure with and without tinnitus.
AB  - Central auditory circuits are influenced by the somatosensory system, a
      relationship that may underlie tinnitus generation. In the guinea pig dorsal
      cochlear nucleus (DCN), pairing spinal trigeminal nucleus (Sp5) stimulation with
      tones at specific intervals and orders facilitated or suppressed subsequent tone
      evoked neural responses, reflecting spike timing-dependent plasticity (STDP).
      Furthermore, after noise-induced tinnitus, bimodal responses in DCN were shifted
      from Hebbian to anti-Hebbian timing rules with less discrete temporal windows,
      suggesting a role for bimodal plasticity in tinnitus. Here, we aimed to determine
      if multisensory STDP principles like those in DCN also exist in primary auditory
      cortex (A1), and whether they change following noise-induced tinnitus. Tone
      evoked and spontaneous neural responses were recorded before and 15 min after
      bimodal stimulation in which the intervals and orders of auditory-somatosensory
      stimuli were randomized. Tone-evoked and spontaneous firing rates were influenced
      by the interval and order of the bimodal stimuli, and in sham-controls Hebbian
      like timing rules predominated as was seen in DCN. In noise-exposed animals with
      and without tinnitus, timing rules shifted away from those found in sham-controls
      to more anti-Hebbian rules. Only those animals with evidence of tinnitus showed
      increased spontaneous firing rates, a purported neurophysiological correlate of
      tinnitus in A1. Together, these findings suggest that bimodal plasticity is also
      evident in A1 following noise damage and may have implications for tinnitus
      generation and therapeutic intervention across the central auditory circuit. 

PMID- 26289462
TI  - Cadence-dependent changes in corticospinal excitability of the biceps brachii
      during arm cycling.
AB  - This is the first study to report the influence of different cadences on the
      modulation of supraspinal and spinal excitability during arm cycling. Supraspinal
      and spinal excitability were assessed using transcranial magnetic stimulation of
      the motor cortex and transmastoid electrical stimulation of the corticospinal
      tract, respectively. Transcranial magnetic stimulation-induced motor evoked
      potentials and transmastoid electrical stimulation-induced cervicomedullary
      evoked potentials (CMEPs) were recorded from the biceps brachii at two separate
      positions corresponding to elbow flexion and extension (6 and 12 o'clock relative
      to a clock face, respectively) while arm cycling at 30, 60 and 90 rpm. Motor
      evoked potential amplitudes increased significantly as cadence increased during
      both elbow flexion (P < 0.001) and extension (P = 0.027). CMEP amplitudes also
      increased with cadence during elbow flexion (P < 0.01); however, the opposite
      occurred during elbow extension (i.e., decreased CMEP amplitude; P = 0.01). The
      data indicate an overall increase in the excitability of corticospinal neurons
      which ultimately project to biceps brachii throughout arm cycling as cadence
      increased. Conversely, changes in spinal excitability as cadence increased were
      phase dependent (i.e., increased during elbow flexion and decreased during elbow
      extension). Phase- and cadence-dependent changes in spinal excitability are
      suggested to be mediated via changes in the balance of excitatory and inhibitory
      synaptic input to the motor pool, as opposed to changes in the intrinsic
      properties of spinal motoneurons. 

PMID- 26289464
TI  - Oculomotor capture by stimuli that signal the availability of reward.
AB  - It is well known that eye movement patterns are influenced by both goal- and
      salience-driven factors. Recent studies, however, have demonstrated that objects
      that are nonsalient and task irrelevant can still capture our eyes if moving our
      eyes to those objects has previously produced reward. Here we demonstrate that
      training such an association between eye movements to an object and delivery of
      reward is not needed. Instead, an object that merely signals the availability of
      reward captures the eyes even when it is physically nonsalient and never relevant
      for the task. Furthermore, we show that oculomotor capture by reward is more
      reliably observed in saccades with short latencies. We conclude that a stimulus
      signaling high reward has the ability to capture the eyes independently of bottom
      up physical salience or top-down task relevance and that the effect of reward
      affects early selection processes. 

PMID- 26289463
TI  - Generalization of motor resonance during the observation of hand, mouth, and eye
      movements.
AB  - Transcranial magnetic stimulation (TMS) of the motor cortex shows that hand
      action observation (AO) modulates corticospinal excitability (CSE). CSE
      modulation alternatively maps low-level kinematic characteristics or higher-level
      features, like object-directed action goals. However, action execution is
      achieved through the control of muscle synergies, consisting of coordinated
      patterns of muscular activity during natural movements, rather than single
      muscles or object-directed goals. This synergistic organization of action
      execution also underlies the ability to produce the same functional output (i.e.,
      grasping an object) using different effectors. We hypothesize that motor system
      activation during AO may rely on similar principles. To investigate this issue,
      we recorded both hand CSE and TMS-evoked finger movements which provide a much
      more complete description of coordinated patterns of muscular activity. Subjects
      passively watched hand, mouth and eyelid opening or closing, which are performing
      non-object-directed (intransitive) actions. Hand and mouth share the same
      potential to grasp objects, whereas eyelid does not allow object-directed
      (transitive) actions. Hand CSE modulation generalized to all effectors, while TMS
      evoked finger movements only to mouth AO. Such dissociation suggests that the two
      techniques may have different sensitivities to fine motor modulations induced by
      AO. Differently from evoked movements, which are sensitive to the possibility to
      achieve object-directed action, CSE is generically modulated by "opening" vs.
      "closing" movements, independently of which effector was observed. We propose
      that motor activities during AO might exploit the same synergistic mechanisms
      shown for the neural control of movement and organized around a limited set of
      motor primitives. 

PMID- 26289466
TI  - Thresholds of cutaneous afferents related to perceptual threshold across the
      human foot sole.
AB  - Perceptual thresholds are known to vary across the foot sole, despite a reported
      even distribution in cutaneous afferents. Skin mechanical properties have been
      proposed to account for these differences; however, a direct relationship between
      foot sole afferent firing, perceptual threshold, and skin mechanical properties
      has not been previously investigated. Using the technique of microneurography, we
      recorded the monofilament firing thresholds of cutaneous afferents and associated
      perceptual thresholds across the foot sole. In addition, receptive field hardness
      measurements were taken to investigate the influence of skin hardness on these
      threshold measures. Afferents were identified as fast adapting [FAI (n = 48) or
      FAII (n = 13)] or slowly adapting [SAI (n = 21) or SAII (n = 20)], and were
      grouped based on receptive field location (heel, arch, metatarsals, toes).
      Overall, perceptual thresholds were found to most closely align with firing
      thresholds of FA afferents. In contrast, SAI and SAII afferent firing thresholds
      were found to be significantly higher than perceptual thresholds and are not
      thought to mediate monofilament perceptual threshold across the foot sole.
      Perceptual thresholds and FAI afferent firing thresholds were significantly lower
      in the arch compared with other regions, and skin hardness was found to
      positively correlate with both FAI and FAII afferent firing and perceptual
      thresholds. These data support a perceptual influence of skin hardness, which is
      likely the result of elevated FA afferent firing threshold at harder foot sole
      sites. The close coupling between FA afferent firing and perceptual threshold
      across foot sole indicates that small changes in FA afferent firing can influence
      perceptual thresholds. 

PMID- 26289465
TI  - Activation of Ih and TTX-sensitive sodium current at subthreshold voltages during
      CA1 pyramidal neuron firing.
AB  - We used dynamic clamp and action potential clamp techniques to explore how
      currents carried by tetrodotoxin-sensitive sodium channels and HCN channels (Ih)
      regulate the behavior of CA1 pyramidal neurons at resting and subthreshold
      voltages. Recording from rat CA1 pyramidal neurons in hippocampal slices, we
      found that the apparent input resistance and membrane time constant were strongly
      affected by both conductances, with Ih acting to decrease apparent input
      resistance and time constant and sodium current acting to increase both. We found
      that both Ih and sodium current were active during subthreshold summation of
      artificial excitatory postsynaptic potentials (EPSPs) generated by dynamic clamp,
      with Ih dominating at less depolarized voltages and sodium current at more
      depolarized voltages. Subthreshold sodium current-which amplifies EPSPs-was most
      effectively recruited by rapid voltage changes, while Ih-which blunts EPSPs-was
      maximal for slow voltage changes. The combined effect is to selectively amplify
      rapid EPSPs. We did similar experiments in mouse CA1 pyramidal neurons, doing
      voltage-clamp experiments using experimental records of action potential firing
      of CA1 neurons previously recorded in awake, behaving animals as command voltages
      to quantify flow of Ih and sodium current at subthreshold voltages. Subthreshold
      sodium current was larger and subthreshold Ih was smaller in mouse neurons than
      in rat neurons. Overall, the results show opposing effects of subthreshold sodium
      current and Ih in regulating subthreshold behavior of CA1 neurons, with
      subthreshold sodium current prominent in both rat and mouse CA1 pyramidal neurons
      and additional regulation by Ih in rat neurons. 

PMID- 26289467
TI  - Hip proprioceptive feedback influences the control of mediolateral stability
      during human walking.
AB  - Active control of the mediolateral location of the feet is an important component
      of a stable bipedal walking pattern, although the roles of sensory feedback in
      this process are unclear. In the present experiments, we tested whether hip
      abductor proprioception influenced the control of mediolateral gait motion.
      Participants performed a series of quiet standing and treadmill walking trials.
      In some trials, 80-Hz vibration was applied intermittently over the right gluteus
      medius (GM) to evoke artificial proprioceptive feedback. During walking, the GM
      was vibrated during either right leg stance (to elicit a perception that the
      pelvis was closer mediolaterally to the stance foot) or swing (to elicit a
      perception that the swing leg was more adducted). Vibration during quiet standing
      evoked leftward sway in most participants (13 of 16), as expected from its
      predicted perceptual effects. Across the 13 participants sensitive to vibration,
      stance phase vibration caused the contralateral leg to be placed significantly
      closer to the midline (by ~2 mm) at the end of the ongoing step. In contrast,
      swing phase vibration caused the vibrated leg to be placed significantly farther
      mediolaterally from the midline (by ~2 mm), whereas the pelvis was held closer to
      the stance foot (by ~1 mm). The estimated mediolateral margin of stability was
      thus decreased by stance phase vibration but increased by swing phase vibration.
      Although the observed effects of vibration were small, they were consistent with
      humans monitoring hip proprioceptive feedback while walking to maintain stable
      mediolateral gait motion. 

PMID- 26289468
TI  - Regional brain responses associated with thermogenic and psychogenic sweating
      events in humans.
AB  - Sweating events occur in response to mental stress (psychogenic) or with
      increased body temperature (thermogenic). We previously found that both were
      linked to activation of common brain stem regions, suggesting that they share the
      same output pathways: a putative common premotor nucleus was identified in the
      rostral-lateral medulla (Farrell MJ, Trevaks D, Taylor NA, McAllen RM. Am J
      Physiol Regul Integr Comp Physiol 304: R810-R817, 2013). We therefore looked in
      higher brain regions for the neural basis that differentiates the two types of
      sweating event. Previous work has identified hemispheric activations linked to
      psychogenic sweating, but no corresponding data have been reported for
      thermogenic sweating. Galvanic skin responses were used to measure sweating
      events in two groups of subjects during either psychogenic sweating (n = 11, 35.3
      +/- 11.8 yr) or thermogenic sweating (n = 11, 34.4 +/- 10.2 yr) while regional
      brain activation was measured by BOLD signals in a 3-Tesla MRI scanner. Common
      regions activated with sweating events in both groups included the anterior and
      posterior cingulate cortex, insula, premotor cortex, thalamus, lentiform nuclei,
      and cerebellum (P(corrected) < 0.05). Psychogenic sweating events were associated
      with significantly greater activation in the dorsal midcingulate cortex, parietal
      cortex, premotor cortex, occipital cortex, and cerebellum. No hemispheric region
      was found to show statistically significantly greater activation with thermogenic
      than with psychogenic sweating events. However, a discrete cluster of activation
      in the anterior hypothalamus/preoptic area was seen only with thermogenic
      sweating events. These findings suggest that the expected association between
      sweating events and brain regions implicated in "arousal" may apply selectively
      to psychogenic sweating; the neural basis for thermogenic sweating events may be
      subcortical.

PMID- 26289470
TI  - The evolution of a distinguished neuroscience journal: a progress report.

PMID- 26289469
TI  - Spatiotemporal profiles of receptive fields of neurons in the lateral posterior
      nucleus of the cat LP-pulvinar complex.
AB  - The pulvinar is the largest extrageniculate thalamic visual nucleus in mammals.
      It establishes reciprocal connections with virtually all visual cortexes and
      likely plays a role in transthalamic cortico-cortical communication. In cats, the
      lateral posterior nucleus (LP) of the LP-pulvinar complex can be subdivided in
      two subregions, the lateral (LPl) and medial (LPm) parts, which receive a
      predominant input from the striate cortex and the superior colliculus,
      respectively. Here, we revisit the receptive field structure of LPl and LPm cells
      in anesthetized cats by determining their first-order spatiotemporal profiles
      through reverse correlation analysis following sparse noise stimulation. Our data
      reveal the existence of previously unidentified receptive field profiles in the
      LP nucleus both in space and time domains. While some cells responded to only one
      stimulus polarity, the majority of neurons had receptive fields comprised of
      bright and dark responsive subfields. For these neurons, dark subfields' size was
      larger than that of bright subfields. A variety of receptive field spatial
      organization types were identified, ranging from totally overlapped to segregated
      bright and dark subfields. In the time domain, a large spectrum of activity
      overlap was found, from cells with temporally coinciding subfield activity to
      neurons with distinct, time-dissociated subfield peak activity windows. We also
      found LP neurons with space-time inseparable receptive fields and neurons with
      multiple activity periods. Finally, a substantial degree of homology was found
      between LPl and LPm first-order receptive field spatiotemporal profiles,
      suggesting a high integration of cortical and subcortical inputs within the LP
      pulvinar complex. 

PMID- 26289471
TI  - Visual coding with a population of direction-selective neurons.
AB  - The brain decodes the visual scene from the action potentials of ~20 retinal
      ganglion cell types. Among the retinal ganglion cells, direction-selective
      ganglion cells (DSGCs) encode motion direction. Several studies have focused on
      the encoding or decoding of motion direction by recording multiunit activity,
      mainly in the visual cortex. In this study, we simultaneously recorded from all
      four types of ON-OFF DSGCs of the rabbit retina using a microelectronics-based
      high-density microelectrode array (HDMEA) and decoded their concerted activity
      using probabilistic and linear decoders. Furthermore, we investigated how the
      modification of stimulus parameters (velocity, size, angle of moving object) and
      the use of different tuning curve fits influenced decoding precision. Finally, we
      simulated ON-OFF DSGC activity, based on real data, in order to understand how
      tuning curve widths and the angular distribution of the cells' preferred
      directions influence decoding performance. We found that probabilistic decoding
      strategies outperformed, on average, linear methods and that decoding precision
      was robust to changes in stimulus parameters such as velocity. The removal of
      noise correlations among cells, by random shuffling trials, caused a drop in
      decoding precision. Moreover, we found that tuning curves are broad in order to
      minimize large errors at the expense of a higher average error, and that the
      retinal direction-selective system would not substantially benefit, on average,
      from having more than four types of ON-OFF DSGCs or from a perfect alignment of
      the cells' preferred directions. 

PMID- 26289473
TI  - Spike sorting of synchronous spikes from local neuron ensembles.
AB  - Synchronous spike discharge of cortical neurons is thought to be a fingerprint of
      neuronal cooperativity. Because neighboring neurons are more densely connected to
      one another than neurons that are located further apart, near-synchronous spike
      discharge can be expected to be prevalent and it might provide an important basis
      for cortical computations. Using microelectrodes to record local groups of
      neurons does not allow for the reliable separation of synchronous spikes from
      different cells, because available spike sorting algorithms cannot correctly
      resolve the temporally overlapping waveforms. We show that high spike sorting
      performance of in vivo recordings, including overlapping spikes, can be achieved
      with a recently developed filter-based template matching procedure. Using
      tetrodes with a three-dimensional structure, we demonstrate with simulated data
      and ground truth in vitro data, obtained by dual intracellular recording of two
      neurons located next to a tetrode, that the spike sorting of synchronous spikes
      can be as successful as the spike sorting of nonoverlapping spikes and that the
      spatial information provided by multielectrodes greatly reduces the error rates.
      We apply the method to tetrode recordings from the prefrontal cortex of behaving
      primates, and we show that overlapping spikes can be identified and assigned to
      individual neurons to study synchronous activity in local groups of neurons. 

PMID- 26289474
TI  - Lower gastrointestinal bleeding in a patient with Crohn's disease and plasma cell
      leukemia in remission.

PMID- 26289472
TI  - Open-loop organization of thalamic reticular nucleus and dorsal thalamus: a
      computational model.
AB  - The thalamic reticular nucleus (TRN) is a shell of GABAergic neurons that
      surrounds the dorsal thalamus. Previous work has shown that TRN neurons send
      GABAergic projections to thalamocortical (TC) cells to form reciprocal, closed
      loop circuits. This has led to the hypothesis that the TRN is responsible for
      oscillatory phenomena, such as sleep spindles and absence seizures. However,
      there is emerging evidence that open-loop circuits are also found between TRN and
      TC cells. The implications of open-loop configurations are not yet known,
      particularly when they include time-dependent nonlinearities in TC cells such as
      low-threshold bursting. We hypothesized that low-threshold bursting in an open
      loop circuit could be a mechanism by which the TRN could paradoxically enhance TC
      activation, and that enhancement would depend on the relative timing of TRN vs.
      TC cell stimulation. To test this, we modeled small circuits containing TC
      neurons, TRN neurons, and layer 4 thalamorecipient cells in both open- and closed
      loop configurations. We found that open-loop TRN stimulation, rather than
      universally depressing TC activation, increased cortical output across a broad
      parameter space, modified the filter properties of TC neurons, and altered the
      mutual information between input and output in a frequency-dependent and T-type
      calcium channel-dependent manner. Therefore, an open-loop model of TRN-TC
      interactions, rather than suppressing transmission through the thalamus, creates
      a tunable filter whose properties may be modified by outside influences onto the
      TRN. These simulations make experimentally testable predictions about the
      potential role for the TRN for flexible enhancement of cortical activation. 

PMID- 26289476
TI  - Onomatopoeias: a new perspective around space, image schemas and phoneme
      clusters.
AB  - Onomatopoeias (<old Greek ?nuomicronMUalphatauomicronpiomicroniotaiotaalpha;
      ?nuomicronMUalpha 'name', piomicroniotaepsilonomega 'I make') are mimetic
      elements representing sounds and lexicalizations of sounds (to smack). A large
      set of problems and studies (based on repositories: Gubern and Gasca in
      Diccionario de onomatopeyas del comic. Cattedra, Madrid, 2008:1.000 lemmas;
      corpora: Zlatev in Sound symbolism and cross-modal iconicity in language,
      Universita Roma Tre, Rome, 2013; algorithms: Asaga et al. in Onomatopedia, pp 601
      612, 2008) has been related to onomatopoeias since Cratilo's analysis of the
      analogical dimension of verbal language. Nonetheless, it is still difficult to
      accept a (semantic, functional or grammatical) descriptive and explicative model
      of onomatopoeia, because the rules that constrain processes of selection and
      construction remain idiosyncratic and variable (Dogana in Le parole dell'incanto.
      FrancoAngeli, Milano, 2002; Catricala 2011). This article proposes a
      classification model based on spatial cognition criteria. The hypothesis
      (Catricala 2011) is that onomatopoeias are related to image schemas (Johnson in
      The body in the mind. University Press, Chicago, 1987), i.e. to the visual
      mapping of a movement. We also refer to force dynamic (Talmy in Language typology
      and lexical description, pp 36-149, 1985; Jackendoff in Semantic structures. MIT
      Press, Cambridge, 1990) as a basic model of conceptual maps (Langacker in Grammar
      and conceptualization. Mouton de Gruyter, Berlin, 1999). Categories are related
      to the presence of specific phonemes and phoneme clusters, while visual patterns
      correspond to different image schemas. The association between specific
      categories of pseudo-onomatopoeias and specific spatial/movement patterns is also
      the object of an experiment focused on onomatopoeia interpretation. Most part of
      data confirms a correlation between image schemas as CONTAINER/CONTAINMENT
      (crunch, plop) or SOURCE-PATH-GOAL (tattarrattat 'shots') and an occlusive
      consonant, while liquid and trill consonants correlate with PATH (vroom). 

PMID- 26289475
TI  - Self-reported strategies in decisions under risk: role of feedback, reasoning
      abilities, executive functions, short-term-memory, and working memory.
AB  - In decisions under objective risk conditions information about the decision
      options' possible outcomes and the rules for outcomes' occurrence are provided.
      Thus, deciders can base decision-making strategies on probabilistic laws. In many
      laboratory decision-making tasks, choosing the option with the highest winning
      probability in all trials (=maximization strategy) is probabilistically regarded
      the most rational behavior. However, individuals often behave less optimal,
      especially in case the individuals have lower cognitive functions or in case no
      feedback about consequences is provided in the situation. It is still unclear
      which cognitive functions particularly predispose individuals for using
      successful strategies and which strategies profit from feedback. We investigated
      195 individuals with two decision-making paradigms, the Game of Dice Task (GDT)
      (with and without feedback), and the Card Guessing Game. Thereafter, participants
      reported which strategies they had applied. Interaction effects (feedback *
      strategy), effect sizes, and uncorrected single group comparisons suggest that
      feedback in the GDT tended to be more beneficial to individuals reporting
      exploratory strategies (e.g., use intuition). In both tasks, the self-reported
      use of more principled and more rational strategies was accompanied by better
      decision-making performance and better performances in reasoning and executive
      functioning tasks. The strategy groups did not significantly differ in most short
      term and working-memory tasks. Thus, particularly individual differences in
      reasoning and executive functions seem to predispose individuals toward
      particular decision-making strategies. Feedback seems to be useful for
      individuals who rather explore the decision-making situation instead of following
      a certain plan. 

PMID- 26289477
TI  - Spatial distribution of attention and inter-hemispheric competition.
AB  - Considerable evidence has demonstrated functional asymmetry in spatial attention
      between the left and right hemispheres. In the present study, we aimed to examine
      the theoretical models of spatial attention by considering distribution and inter
      hemispheric competition in neurologically healthy participants. Participants
      searched for a green circle target among green diamond non-targets in the
      presence or absence of a red singleton. Assuming that the salient singleton would
      increase the activation of the corresponding hemisphere, we manipulated the sides
      of the singleton visual fields and target visual fields. When the salient
      singleton was presented to the right visual field, target detection was faster
      for left visual field targets than for right visual field targets. In contrast,
      when the salient singleton was presented to the left visual field, target
      detection time was equivalent for left and right visual field targets. These
      results suggest that when the perceptually salient singleton acts as an
      activator, distribution of attention differs depending on the activated
      hemisphere induced by inter-hemispheric competition. These findings are in line
      with Kinsbourne's opponent processor theory. 

PMID- 26289478
TI  - Unilateral eccentric resistance training: A direct comparison between isokinetic
      and dynamic constant external resistance modalities.
AB  - Aim of the study was to compare the effects of unilateral eccentric-only training
      using constant velocity vs. constant external load. Forty-seven participants were
      randomized in isokinetic (IK), dynamic constant external resistance (DCER)
      unilateral eccentric training or control groups. Knee extension 1RM and
      isometric, eccentric and concentric knee extensors peak torque, as well as
      changes in vastus lateralis fascicle pennation angle, fascicle length, muscle
      thickness, and quadriceps fat-free mass were measured. Both IK and DCER training
      consisted in 5 * 8 eccentric-only repetitions, 2d/w, for 6 weeks. IK and DCER
      training sessions were matched for total volume. After training, both IK and DCER
      similarly increased 1RM (respectively, +4.4 kg, CI95% 1.8-7.0 and +5.5 kg, CI95%
      3.3-7.9), isometric (respectively, +34.5 N/m, CI95% 23.0-45.9 and +15.8, CI95%
      5.4-26.2) and concentric peak torque (respectively, +17.0 N/m, CI95% 6.6 to +27.4
      and 12.2 CI95% 2.8-21.7). IK increased eccentric peak torque significantly more
      than DCER (respectively, +84.2 N/m, CI95% 66.3-102.1 and +38.2 N/m, CI95% 21.9
      54.4). Both IK and DCER similarly increased fascicle length (respectively, +14.7
      mm, CI95% 5.4-24.0 and +14.4 mm, CI95% 5.4-23.3) and muscle thickness
      (respectively, +3.3 mm, CI95% 1.5-5.1, and +4.1 mm, CI95% 2.5-5.7). Matching the
      training volume resulted in similar adaptations comparing eccentric-only IK or
      DCER resistance training. Both in rehabilitation and in training practice, the
      use of easily available gym devices can be a good substitute for expensive and
      often unavailable IK devices.

PMID- 26289480
TI  - Modulation of reactive response to slip-like perturbations: effect of explicit
      cues on paretic versus non-paretic side stepping and fall-risk.
AB  - This study aimed to examine the effect of explicit cuing on reactive stepping
      with the paretic limb during slip-like perturbations in stroke survivors and to
      identify differences in postural stability and fall-risk while stepping with
      either limb. Eleven chronic hemiparetic stroke survivors received slip-like
      stance perturbations in no-cue (implicit, no instructions) and cued (explicit,
      instructions to step with paretic limb) conditions. Frequency of stepping with
      the paretic limb was recorded. Differences between non-paretic and paretic steps
      for falls, number of compensatory steps, relative center-of-mass position (X
      COM/BOS), and velocity (X(COM/BOS)), and vertical limb support (hip descent-Z
      hip) were analyzed. Stepping with the paretic limb increased from 6% in no-cue
      condition to 42% in cued condition with no significant difference in number of
      falls and steps regardless of stepping limb. At liftoff of the compensatory step,
      stability was greater (anterior X COM/BOS) with paretic than non-paretic limb
      stepping whereas, at touchdown (TD) of the step, stability with paretic limb
      reduced (posterior X COM/BOS and X(COM/BOS)) due to a smaller compensatory step
      taken with the paretic versus non-paretic limb. There was no significant
      difference in peak Z hip regardless of stepping limb; however, the timing of peak
      Z hip differed (occuring prior to TD during non-paretic stepping and post-TD
      during paretic stepping). Thus, fall onset was earlier with non-paretic versus
      paretic stepping. The results support that explicit cueing can facilitate
      initiation of reactive step from the paretic limb as compared with the no-cue
      condition. Stepping with the paretic limb in the cued condition however altered
      time of fall onset. Regardless of the stepping side, individuals demonstrated a
      fall risk suggesting the need for interventions focusing on reactive step
      training with both the limbs.

PMID- 26289479
TI  - Structural mechanism for signal transduction in RXR nuclear receptor
      heterodimers.
AB  - A subset of nuclear receptors (NRs) function as obligate heterodimers with
      retinoid X receptor (RXR), allowing integration of ligand-dependent signals
      across the dimer interface via an unknown structural mechanism. Using nuclear
      magnetic resonance (NMR) spectroscopy, x-ray crystallography and
      hydrogen/deuterium exchange (HDX) mass spectrometry, here we show an allosteric
      mechanism through which RXR co-operates with a permissive dimer partner,
      peroxisome proliferator-activated receptor (PPAR)-gamma, while rendered generally
      unresponsive by a non-permissive dimer partner, thyroid hormone (TR) receptor.
      Amino acid residues that mediate this allosteric mechanism comprise an
      evolutionarily conserved network discovered by statistical coupling analysis
      (SCA). This SCA network acts as a signalling rheostat to integrate signals
      between dimer partners, ligands and coregulator-binding sites, thereby affecting
      signal transmission in RXR heterodimers. These findings define rules guiding how
      NRs integrate two ligand-dependent signalling pathways into RXR heterodimer
      specific responses. 

PMID- 26289481
TI  - Concurrent adaptation to opposing visuomotor rotations by varying hand and body
      postures.
AB  - When reaching towards objects, the human central nervous system (CNS) can
      actively compensate for two different perturbations simultaneously (dual
      adaptation), though this does not simply occur upon presentation. Dual adaptation
      is made more difficult when the desired trajectories and targets are identical
      and hence do not cue the impending perturbation. In cases like these, the CNS
      requires contextual cues in order to predict the dynamics of the environment. Not
      all cues are effective at facilitating dual adaptation. In two experiments, we
      investigated the efficacy of two contextual cues that are intrinsic to the CNS,
      namely hand as well as body posture in concurrently adapting to two opposing
      visuomotor rotations. For the hand posture experiment, we also look at the role
      of extended training. Participants reached manually to visual targets with their
      unseen hand represented by a cursor that was rotated either 30 degrees  clockwise
      or counterclockwise, determined randomly on each reach. Each rotation was
      associated with a distinct hand posture (a precision or power grip, respectively)
      in one experiment and a distinct body rotation (10 degrees  leftward or rightward
      turn of the seat, respectively, while fixating straight) in the second
      experiment. Critically, the targets (and thus, the required cursor trajectories)
      were identical in both rotations. We found that how people held the tool or
      oriented their body while reaching is sufficient for concurrently adapting
      separate visuomotor mappings such that over time, reach errors significantly
      decrease. Extended practice did not lead to further benefits though. These
      findings suggest that when the required cursor movements are identical for
      different visuomotor mappings, dual adaptation is still possible given sufficient
      intrinsic contextual cues. 

PMID- 26289482
TI  - Anticipatory gaze strategies when grasping moving objects.
AB  - Grasping moving objects involves both spatial and temporal predictions. The hand
      is aimed at a location where it will meet the object, rather than the position at
      which the object is seen when the reach is initiated. Previous eye-hand
      coordination research from our laboratory, utilizing stationary objects, has
      shown that participants' initial gaze tends to be directed towards the eventual
      location of the index finger when making a precision grasp. This experiment
      examined how the speed and direction of a computer-generated block's movement
      affect gaze and selection of grasp points. Results showed that when the target
      first appeared, participants anticipated the target's eventual movement by
      fixating well ahead of its leading edge in the direction of eventual motion. Once
      target movement began, participants shifted their fixation to the leading edge of
      the target. Upon reach initiation, participants then fixated towards the top edge
      of the target. As seen in our previous work with stationary objects, final
      fixations tended towards the final index finger contact point on the target.
      Moreover, gaze and kinematic analyses revealed that it was direction that most
      influenced fixation locations and grasp points. Interestingly, participants
      fixated further ahead of the target's leading edge when the direction of motion
      was leftward, particularly at the slower speed-possibly the result of mechanical
      constraints of intercepting leftward-moving targets with one's right hand. 

PMID- 26289483
TI  - Reduced object-based perception in the near-hand space.
AB  - Previous studies have shown that hand proximity changes visual perception (Abrams
      et al. in Cognition 107(3):1035-1047, 2008). The present study examined the
      effects of hand proximity on object-based perception. In three experiments,
      participants viewed stimuli that were either near to or far from their hands. The
      target stimulus appeared, after a cue, in one of two rectangular objects: either
      at the location that had been previously cued, at the uncued end of the cued
      object, or in the uncued object. We found a significantly reduced same-object
      benefit in reaction time for stimuli near the hands in one experiment.
      Interestingly, we observed a same-object cost in sensitivity for stimuli near the
      hands in another experiment. The results reveal that object-based perception is
      disrupted in the near-hand space. This is consistent with previous findings
      revealing altered visual processing near the hands. 

PMID- 26289484
TI  - Effects of postural and voluntary muscle contraction on modulation of the soleus
      H reflex by transcranial magnetic stimulation.
AB  - Modulation of spinal reflexes depends largely on the integrity of the
      corticospinal tract. A useful method to document the influence of descending
      tracts on reflexes is to examine the effects of transcranial magnetic stimulation
      (TMS) on the soleus H reflex elicited by posterior tibial nerve electrical
      stimuli (PTS). In 12 healthy volunteers, we investigated how postural or
      voluntary muscle contraction modified such descending modulation. We first
      characterized the effects of TMS at 95 % of motor threshold for leg responses on
      the H reflex elicited by a preceding PTS at inter-stimuli intervals (ISIs)
      between 0 and 120 ms at rest and, then, during voluntary plantar flexion (pf),
      dorsal flexion (df), and standing still (ss). During pf, there was an increase in
      the facilitation of the H reflex at ISIs 0-20 ms. During df, there were no
      effects of TMS on the H reflex. During ss, there was inhibition at ISIs 40-60 ms.
      Our observations suggest that muscle contraction prevails over the baseline
      effects of TMS on the soleus H reflex. While contraction of the antagonist (df)
      suppressed most of the effects, contraction of the agonist had different effects
      depending on the type of activity (pf or ss). The characterization of the
      interaction between descending corticospinal volleys and segmental peripheral
      inputs provides useful information on motor control for physiological research
      and further understanding of the effects of spinal cord lesions.

PMID- 26289485
TI  - Attention deficit hyperactivity disorder and substance misuse: an evaluation of
      causal hypotheses and treatment considerations.
AB  - Attention deficit hyperactivity disorder (ADHD) is known to co-occur with
      substance misuse at a high rate. This has important health and legal implications
      for those with ADHD. Mechanisms that may influence drug use among those with ADHD
      are discussed and evaluated in this review, including self-medication, behavioral
      disinhibition, comorbidity, and sensitization. While no one hypothesis is able to
      explain the complex phenomenon of drug taking behaviors, it is likely that self
      medication, disinhibition and comorbidity play a part, with little evidence for
      sensitization. The development of efficacious treatment is necessary to help
      those with this debilitating comorbidity, as there are currently few evidence
      based interventions. 

PMID- 26289486
TI  - The safety, efficacy and tolerability of Abilify Maintena for the treatment of
      schizophrenia.
AB  - Relapse in schizophrenia has been associated with poor adherence to oral
      medication. A possible method to optimize medication adherence could be to switch
      patients from oral to depot medication. In this respect, aripiprazole long acting
      injectable (ALAI) significantly delayed time to impending relapse when compared
      with placebo (p < 0.0001), while ALAI was generally well tolerated during both
      short-term and long-term studies. A literature search, using PubMed was conducted
      to identify relevant publications. Available evidence suggests that ALAI may be a
      viable treatment option for patients with schizophrenia, but before it can be
      concluded whether or not all schizophrenia patients could benefit from a switch
      to depot formulations, several questions remain to be answered. Thus, there is a
      great need for randomized controlled trials comparing depot medications with
      their oral equivalents. 

PMID- 26289487
TI  - The safety and efficacy of fosphenytoin for the treatment of status epilepticus.
AB  - Fosphenytoin, a water-soluble prodrug of the antiepileptic drug phenytoin, is
      entirely and rapidly converted to this antiepileptic drug. The mechanism of
      action of fosphenytoin is related to the blockade of voltage-operated sodium
      channels. It was developed in order to obtain a phenytoin-like drug with improved
      water solubility. Its maximal plasma concentration is achieved within 90-190 min
      following intramuscular administration with bioavailability being complete after
      intravenous injection. The main indications for fosphenytoin are the treatment of
      convulsive status epilepticus and the prevention/management of seizures during
      neurosurgery. Adverse effects of fosphenytoin may include: cardiovascular events
      (hypotension, arrhythmias), paresthesias or pruritus or some central events -
      somnolence, headache, dizziness, nystagmus and ataxia. The incidence of purple
      glove syndrome (edema, discoloration and pain distal to the site of intravenous
      administration) is less frequent than after phenytoin. Generally, the development
      of fosphenytoin aimed at avoiding complications associated with parenteral use of
      phenytoin. 

PMID- 26289488
TI  - Physical activity and brain development.
AB  - Brain development is a complex process, and stimuli during this developmental
      period may modulate the brain's functional maturation and determine its lifelong
      integrity. Human and animal studies have shown that environmental stimuli such as
      physical activity habits seem to have a favorable influence on brain development.
      Research on humans has demonstrated improvement in cognitive performance in the
      children of women who exercised regularly throughout pregnancy and in individuals
      who were physically active during childhood and adolescence. Investigations using
      animal models have also reported that physical activity improves the cognitive
      function of developing rats. In this review, we will present the neurobiological
      mechanisms of such effects. 

PMID- 26289489
TI  - Long-term effectiveness of rivastigmine patch or capsule for mild-to-severe
      Alzheimer's disease: a meta-analysis.
AB  - AIM: To evaluate the long-term effectiveness of rivastigmine patch or capsule on
      mild to severe Alzheimer's disease (AD). METHOD: We performed a meta-analysis of
      17 studies regarding the treatment effectiveness of rivastigmine patch or capsule
      on mild-to-severe AD. RESULTS: Significant difference exists between treatment
      with rivastigmine patch or capsule and placebo groups (p-value < 0.001). In the
      Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) score
      evaluation, a negative weighted mean difference (WMD) was observed in overall and
      mild-moderate groups after rivastigmine treatment. And in ADAS-ADL score
      evaluation, a positive WMD was observed in overall groups after rivastigmine
      treatment. Moreover, WMD value is lower in patch administration subgroup compared
      to that of capsule administration subgroup. CONCLUSION: Rivastigmine treatment
      shows a positive result of improving the condition of patients with mild-to
      severe AD. Patch administration shows a stronger effect on decreasing ADAS-Cog
      score compared to capsule administration.

PMID- 26289490
TI  - Dual tasking in Parkinson's disease: should we train hazardous behavior?
AB  - Dual-task (DT) circumstances aggravate gait disorders in Parkinson's disease (PD)
      and are associated with an increased risk of falling and reduced functional
      mobility. Clinical rehabilitation guidelines for PD consider DT interventions as
      potentially hazardous and recommend avoiding them in daily life. The current
      article challenges this notion and addresses the necessity of implementing DT
      training in PD. First, underlying reasons for DT interference in PD and current
      theoretical models are discussed. Subsequently, different training approaches to
      tackle DT difficulties are put forward. Finally, the effectiveness and
      limitations of DT training in PD are reviewed. We conclude that there is a need
      for DT interventions in PD and recommend randomized, power-based studies to
      further test their efficacy. 

PMID- 26289491
TI  - Recognition and treatment of neuropsychiatric disturbances in Parkinson's
      disease.
AB  - The non-motor symptoms of Parkinson's disease (PD) have been attracting
      increasing attention due to their ubiquitous nature and their often devastating
      effects on the quality of life. Behavioral problems in PD include dementia,
      depression, apathy, fatigue, anxiety, psychosis, akathisia, personality change,
      sleep disorders and impulse control disorders. Some of these are intrinsic to the
      neuropathology while others occur as an interplay between pathology, psychology
      and pharmacology. While few data exist for guiding therapy, enough is known to
      guide therapy in a rational manner. 

PMID- 26289492
TI  - A possible primary carcinoid (neuroendocrine) tumour of the skin with multiple
      metastases.

PMID- 26289493
TI  - Correction: Synergism between genome sequencing, tandem mass spectrometry and bio
      inspired synthesis reveals insights into nocardioazine B biogenesis.
AB  - Correction for 'Synergism between genome sequencing, tandem mass spectrometry and
      bio-inspired synthesis reveals insights into nocardioazine B biogenesis' by Norah
      Alqahtani et al., Org. Biomol. Chem., 2015, 13, 7177-7192. 

PMID- 26289494
TI  - Effective Amyloid Defibrillation by Polyhydroxyl-Substituted Squaraine Dyes.
AB  - With an objective to develop beta-amyloid destabilizing agents, we have
      investigated the interactions of a few water-soluble near-infrared (NIR)
      absorbing squaraine dyes 1-3 with lysozyme and its amyloid aggregates through
      photophysical and biophysical techniques. These dyes exhibited strong
      interactions with lysozyme and beta-amyloids in addition to serum albumins as
      evidenced by the absorption and emission changes. The interactions were found to
      be spontaneous with association constant values in the range of approximately
      10(4)-10(5)  m(-1), as confirmed through half-reciprocal analysis and isothermal
      calorimetric measurements. Uniquely, such effective interactions of the dyes have
      led to the complete disassembly of the beta-amyloid fibrillar structures to form
      spherical particles approximately 350 nm in size, as confirmed through
      photophysical, thioflavin assay, circular dichroism (CD), atomic force microscopy
      (AFM), TEM, and selected-area electron diffraction (SAED) techniques. These
      results demonstrate that the squaraine dyes 1-3 under investigation act as
      effective protein-labelling and destabilizing agents of the protein
      amyloidogenesis.

PMID- 26289495
TI  - Maximum penalized likelihood estimation in semiparametric mark-recapture-recovery
      models.
AB  - We discuss the semiparametric modeling of mark-recapture-recovery data where the
      temporal and/or individual variation of model parameters is explained via
      covariates. Typically, in such analyses a fixed (or mixed) effects parametric
      model is specified for the relationship between the model parameters and the
      covariates of interest. In this paper, we discuss the modeling of the
      relationship via the use of penalized splines, to allow for considerably more
      flexible functional forms. Corresponding models can be fitted via numerical
      maximum penalized likelihood estimation, employing cross-validation to choose the
      smoothing parameters in a data-driven way. Our contribution builds on and extends
      the existing literature, providing a unified inferential framework for
      semiparametric mark-recapture-recovery models for open populations, where the
      interest typically lies in the estimation of survival probabilities. The approach
      is applied to two real datasets, corresponding to gray herons (Ardea cinerea),
      where we model the survival probability as a function of environmental condition
      (a time-varying global covariate), and Soay sheep (Ovis aries), where we model
      the survival probability as a function of individual weight (a time-varying
      individual-specific covariate). The proposed semiparametric approach is compared
      to a standard parametric (logistic) regression and new interesting underlying
      dynamics are observed in both cases. 

PMID- 26289496
TI  - Effects of leisure activities at home on perceived care burden and the endocrine
      system of caregivers of dementia patients: a randomized controlled study.
AB  - BACKGROUND: Psychological stress associated with caregiving is thought to
      underlie the high incidence of hypertension, ischemic heart disease, and
      mortality, as well as reduced immune function, among caregivers of dementia
      patients. Here, we examined the effects of periodic leisure activities performed
      by caregivers of dementia patients with care recipients at home on perceived care
      burden and levels of stress hormones. METHODS: Participants were 42 caregivers
      aged >= 65 years of patients diagnosed with Alzheimer's dementia. They were
      randomly assigned to intervention and non-intervention groups. The intervention
      group underwent a leisure activity program (30 min/3 times/week for 24 weeks)
      with the care recipient, and the control group underwent normal care activities.
      RESULTS: The Zarit Burden Interview (ZBI) score, a subjective indicator of care
      burden, significantly decreased after intervention in the intervention group (p <
      0.05), whereas no difference was observed in the control group. No significant
      changes were observed in adrenaline, noradrenaline, dopamine, and cortisol levels
      in both groups. CONCLUSIONS: The lack of changes in stress hormone levels despite
      a decrease in subjective care burden in the intervention group might be explained
      by the effects of the chosen leisure activity on the neuroendocrine system. Our
      findings suggest that periodic leisure activities can reduce perceived care
      burden among caregivers of dementia patients. However, in order to evaluate
      accurately the effects of leisure activities of the present study, long-term
      follow-up of both caregivers and care recipients is necessary. The Nagoya
      University Department of Medicine Ethics Committee Clinical Trials Registry
      Number is 1290.

PMID- 26289497
TI  - Sativex((r)) and clinical-neurophysiological measures of spasticity in
      progressive multiple sclerosis.
AB  - Despite the proven efficacy of Sativex((r)) (9-delta-tetrahydrocannabinol plus
      cannabidiol) oromucosal spray in reducing spasticity symptoms in multiple
      sclerosis (MS), little is known about the neurophysiological correlates of such
      effects. The aim of the study was to investigate the effects of Sativex on
      neurophysiological measures of spasticity (H/M ratio) and corticospinal
      excitability in patients with progressive MS. This was a randomized, double
      blind, placebo-controlled, crossover study. Consecutive subjects with progressive
      MS and lower limb spasticity referred to our center were randomized to 4 weeks'
      treatment (including 2 weeks' titration) with Sativex or placebo, with crossover
      after a 2-week washout. Clinical and neurophysiological measures (H/M ratio and
      cortical excitability) of spasticity were assessed. The H/M ratio was the primary
      outcome, with sample size calculation of 40 patients. Of 44 recruited patients,
      34 were analyzed due to 6 drop-outs and 4 exclusions, which lowered the power of
      the study to show differences between treatments. Neurophysiological measures did
      not differ significantly according to treatment and did not correlate
      significantly with clinical response. Response on the modified Ashworth scale (at
      least 20 % improvement) was significantly more frequent after Sativex than
      placebo (50 vs 23.5 %; p = 0.041; McNemar). Side effects did not differ
      significantly according to treatment. Our findings confirm the clinical benefit
      of Sativex on MS spasticity. The lack of corresponding changes in corticospinal
      excitability and on the monosynaptic component, of the stretch reflex, although
      in a limited sample size, points to the involvement of other spinal and
      supraspinal mechanisms in the physiopathology of spasticity in progressive MS.

PMID- 26289498
TI  - Terahertz detectors arrays based on orderly aligned InN nanowires.
AB  - Nanostructured terahertz detectors employing a single semiconducting nanowire or
      graphene sheet have recently generated considerable interest as an alternative to
      existing THz technologies, for their merit on the ease of fabrication and above
      room-temperature operation. However, the lack of alignment in nanostructure
      device hindered their potential toward practical applications. The present work
      reports ordered terahertz detectors arrays based on neatly aligned InN nanowires.
      The InN nanostructures (nanowires and nano-necklaces) were achieved by chemical
      vapor deposition growth, and then InN nanowires were successfully transferred and
      aligned into micrometer-sized groups by a "transfer-printing" method. Field
      effect transistors on aligned nanowires were fabricated and tested for terahertz
      detection purpose. The detector showed good photoresponse as well as low noise
      level. Besides, dense arrays of such detectors were also fabricated, which
      rendered a peak responsivity of 1.1 V/W from 7 detectors connected in series. 

PMID- 26289499
TI  - Reliability and Validity of the Vietnamese Depression Interview (VDI).
AB  - Current instruments used to aid in the diagnosis of psychological disorders have
      limited effectiveness with clients from Asian backgrounds. The Vietnamese
      Depression Interview (VDI) is a diagnostic instrument created to assess the
      presence of current and lifetime history of major depressive disorder
      specifically among Vietnamese refugees and immigrants. The purpose of the present
      study is to provide a description of the VDI, while also noting it as a reliable
      and valid means by which to assess depression in Vietnamese individuals. Using
      the Longitudinal, Expert, and All Data (LEAD; Spitzer in Compr Psychiatry 24:399
      411, 1983) standard and the VDI, experienced clinicians conducted the diagnosis
      process with 127 Vietnamese refugees and immigrants. Assessment of the
      reliability and validity of the VDI yielded good to excellent AUC and kappa
      values, indicating the reliability of the VDI and the agreement between the LEAD
      procedure and the VDI. These study results imply that the VDI performs
      successfully as a diagnostic instrument specifically created for Vietnamese
      refugees and immigrants in their native language. Current and future
      contributions of the VDI with Vietnamese individuals are discussed.

PMID- 26289500
TI  - A Path Analysis of Mental Health Among Thai Immigrant Employees in Pranakron Si
      Ayutthaya Province.
AB  - The aims of this research were to study both direct and indirect path analyses of
      mental health, and to analyse a causal relationship of each variable. A cross
      sectional study used stratified random sampling to select Thai immigrant
      employees in Pranakron Si Ayutthaya Province, Thailand. General data were
      analysed by number and percentage. The mental health variable was measured by
      THMHI-15. The latter was analysed by general statistic, and a path analysis. The
      results found that job conditions and distance travelled between house and
      workplace had a direct effect on mental health with a standardised regression
      weight of 0.581, and -0.443, respectively (p value <0.01). It was found that
      housing conditions had no effect on mental health. The income variable had a
      direct influence on mental health with a standardised regression weight of 0.68
      (p value <0.01). This research indicated that job conditions were an important
      factor related to mental health.

PMID- 26289501
TI  - Impact of the Boston Marathon Bombing and Its Aftermath on Refugees and Survivors
      of Torture.
AB  - On April 15, 2013, Boston residents and guests gathered for the Boston Marathon.
      Two explosives at the finish line killed three people and injured hundreds of
      others. As part of our clinical encounters, patients of the Boston Center for
      Refugee Health & Human Rights were asked about the marathon bombing. We were
      concerned about the high level of armed security as many of our patients had been
      detained in their countries of origin. Eighty patients seen between April 16 and
      July 7, 2013 were asked about their experience of the Boston Marathon bombing and
      its aftermath. A retrospective chart review was undertaken and data analyzed
      using Atlas.ti & SPSS. Approximately 86 % of those interviewed were reminded of
      their past trauma. The following themes emerged: triggering and trauma related
      symptoms, content specific cognitive schemas, recognition of the universality of
      violence, fears of discrimination, issues surrounding safety, and specific
      concerns of Muslims.

PMID- 26289503
TI  - Ex vivo pancreaticoduodenectomy and liver autotransplantation for pancreatic head
      tumor with extensive involvement of the hepatoduodenal ligament.

PMID- 26289502
TI  - Reported Health Behaviour Changes after a Diagnosis of Gestational Diabetes
      Mellitus among Ethnic Minority Women Living in Canada.
AB  - The aim of this cross-sectional study was to examine differences in health
      behaviours among ethnic minority and Caucasian women after a diagnosis of
      gestational diabetes mellitus (GDM). Data were derived from medical charts and a
      questionnaire among a multi-ethnic cohort of 898 Canadian pregnant women
      diagnosed with GDM attending prenatal diabetes clinics in Ontario, Canada. Health
      behaviours were compared between ethnic minority and Caucasian women, adjusting
      for relevant covariates. The mean age was 33.9 +/- 6.1 years; 60.0 % self
      reported to be part of an ethnic minority group. After adjustment for socio
      demographic, behavioural and clinical characteristics, ethnic minority women were
      more likely to report reducing their meal portion sizes (odds ratio [OR] 1.98;
      95.0 % confidence interval [CI] 1.20-3.26) and increasing their physical activity
      (OR 1.71; 95.0 % CI 1.12-2.62) in response to a GDM diagnosis compared to
      Caucasian women. Ethnic minority women were more likely to report changes in
      health behaviours after a GDM diagnosis. Further research is needed to determine
      the impact of these findings on maternal health and perinatal outcomes, during
      and after delivery.

PMID- 26289504
TI  - Curative Effects of Different Sequences of Vessel Interruption During the
      Completely Thoracoscopic Lobectomy on Early Stage Non-Small Cell Lung Cancer.
AB  - OBJECTIVE: To study the correlation between prognosis and different sequences of
      pulmonary artery and vein interruption during completely thoracoscopic lobectomy
      for early stage non-small cell lung cancer. METHODS: Retrospective analysis of
      334 cases underwent completely thoracoscopic lobectomy, which were identified as
      stage I~II non-small cell lung cancer by pathology. They were divided into three
      groups according to the order of vessel interruption: pulmonary vein first (Group
      V, n = 174), pulmonary artery first (Group A, n = 93), and artery-vein-artery
      group (Group M, n = 67). Their preoperative and operative conditions, and the
      postoperative survival, recurrence were compared. RESULTS: Group A had less cases
      with history of smoking but more with history of pulmonary infection. The average
      bleeding amount during the operation in Group A is significantly less Group V,
      and Group M fell in between them. The duration of operation and postoperative
      complications were similar among the three groups. The types of tumor recurrence
      were also similar, which were mostly distant metastasis. There was no
      statistically significant difference in tumor-free survival and overall survival
      among the three groups. CONCLUSIONS: For the treatment of stage I~II non-small
      cell lung cancer using completely thoracoscopic lobectomy, pulmonary artery
      interruption first can reduce the bleeding amount without affecting the operative
      difficulty and postoperative complications. The sequence of vessel interruption
      during lobectomy by thoracoscopic surgery would not affect tumor recurrence,
      metastasis and survival.

PMID- 26289505
TI  - Nonalcoholic fatty liver disease: Synopsis of current developments.
AB  - Non-alcoholic fatty liver disease (NAFLD) which is defined as the accumulation of
      fat>5% of liver weight is increasingly becoming an important cause of chronic
      liver disease. This article tries to chronicle advances that have occurred in the
      understanding of the pathogenesis, pathology as well as the management of this
      disease. We have done a Medline search on published work on the subject and
      reviewed major conference proceedings in the preceding years. The Pathogenesis
      involves a multi-hit process in which increased accumulation of triglycerides in
      face of insulin resistance results in increased susceptibility to inflammatory
      damage mediated by increased expression of inflammatory cytokines and adipokines,
      oxidative stress and mitochondrial dysfunction, endoplasmic reticulum stress and
      gut derived endotoxemia. An interplay of multiple metabolic genetic expression
      and environmental factors however determine which patient with NAFLD will
      progress from simple steatosis to non-alcoholic steatohepatitis (NASH) and liver
      cirrhosis. The minimum criteria for diagnosis of NASH are steatosis, ballooning
      and lobular inflammation; fibrosis is not required. The NASH Clinical Research
      Network (CRN), histological scoring system is used to grade and stage the disease
      for standardization. The management of NAFLD consists of treating liver disease
      as well as associated metabolic co-morbidities such as obesity, hyperlipidaemia,
      insulin resistance and type 2 diabetes mellitus (T2DM). Patient education is
      important as their insight and commitment is pivotal, and lifestyle modification
      is the first line of treatment. Improvement in liver histology in non-diabetic
      NASH patients has been reported with use of Vitamin E. Other liver-related
      therapies under investigations include pentoxyfiylins, Caspar inhibitors,
      Resveratrol as well as probiotics. The prognosis (both overall and liver-related
      mortality) for simple steatosis is not different from that of the general
      population however.

PMID- 26289506
TI  - Shaping ability of two M-wire and two traditional nickel-titanium instrumentation
      systems in S-shaped resin canals.
AB  - AIMS: The aim of this study was to evaluate the shaping effects of two M-wire and
      two traditional nickel-titanium (NiTi) rotary systems in simulated S-shaped resin
      canals. SUBJECTS AND METHODS: Forty simulated S-shaped canals in resin blocks
      were instrumented with two traditional (ProTaper, Sendoline S5) and two M-wire
      (WaveOne, GT series X) NiTi systems according to the manufacturers' instructions.
      Ten resin blocks were used for each system. Pre- and post-instrumentation images
      were captured using a stereomicroscope and superimposed with an image program.
      Canal transportation, material removal, and aberrations were evaluated and
      recorded as numeric parameters. STATISTICAL ANALYSIS USED: Data were analyzed
      using one-way ANOVA and post-hoc Tukey tests with a 95% confidence interval.
      RESULTS: There were significant differences between systems in terms of
      transportation and material removal (P<0.05). Coronal danger zone was the most
      common aberration. CONCLUSIONS: Within the limits of this ex vivo study, it was
      found that the manufacturing methods (M-wire or traditional NiTi) and kinematics
      (rotary or reciprocating motion) did not affect the shaping abilities of the
      systems. The extended file designs of highly tapered NiTi systems (ProTaper,
      WaveOne) resulted in greater deviations from the original root canal trace and
      more material removal when compared to less tapered systems (Sendoline S5, GT
      series X).

PMID- 26289507
TI  - Pattern of acquired heart diseases among children seen in Sokoto, North-Western
      Nigeria.
AB  - BACKGROUND: Acquired heart diseases (AHDs) are serious but largely preventable
      diseases. They are highly prevalent in developing countries where poverty,
      illiteracy, and poor socioeconomic conditions still pose a significant challenge.
      The prevalence and pattern of AHD among children have not been previously
      documented within the study area. OBJECTIVES: To determine the pattern and
      outcome of AHDs among children in Sokoto, North-Western Nigeria. SUBJECTS AND
      METHODS: A prospective study conducted at the Pediatric Department of Usmanu
      Danfodiyo University Teaching Hospital, Sokoto, Nigeria from 1st July 2009 to
      30th June 2014. Data from all the subjects with AHD were analyzed using
      Statistical Package for Social Sciences. RESULTS: Of the 3810 children, 110
      (2.9%) children were diagnosed with AHD over the study period. The mean age of
      the subjects was 10.4+/-3.4 years with M: Fratio of 1.2:1. Rheumatic heart
      disease (RHD) was the most common AHD seen in 47 (42.7%) patients, followed by
      dilated cardiomyopathy/myocarditis in 36 (32.7%) and pericardial effusion in 12
      (10.9%) patients. Endomyocardial fibrosis was seen in 7 (6.4%) patients while
      infective endocarditis and Kawasaki disease occurred in 6 (5.5%) and 2 (1.8%)
      patients respectively. Mortality rate was 17.3%. Commonly observed co-morbidities
      included heart failure, bronchopneumonia, and pulmonary hypertension. CONCLUSION:
      The pattern of AHD is similar to other studies in developing countries, with RHD
      being the most prevalent. There is a need for increased emphasis on primary
      prevention to reduce the burden of these diseases in the study area.

PMID- 26289508
TI  - Complex and compound odontomas: Analysis of 69 cases and a rare case of erupted
      compound odontoma.
AB  - OBJECTIVE: The purpose of this study was to analyze clinic and radiologic
      features of the 69 odontoma cases and present a rare case of erupted compound
      odontoma in the oral cavity. MATERIAL AND METHODS: The 69 cases were analyzed
      with regard to the following parameters: age, gender, location, associated
      unerupted teeth, missing teeth, radiological and histopathological features and
      treatment protocols. RESULTS: Of the 69 cases, 49 were compound odontoma and 20
      were complex odontoma. There was a female predilection for both compound and
      complex odontomas. Compound odontoma occurred more often in the anterior region
      of the jaws; complex lesions occurred more often at the posterior mandible. The
      most common clinical manifestations were the retention of permanent teeth.
      CONCLUSION: Compound odontomas rarely erupt into the mouth. The presented case is
      the 13 th case of erupted compound odontoma reported in the literature. The
      treatment of choice is surgical removal of the odontoma. In the case of odontomas
      associated to impacted teeth, the teeth should be preserved in wait of
      spontaneous eruption, or alternatively fenestration followed by orthodontic
      traction is indicated. Regular follow-up period is crucial to evaluate the
      prognosis of these teeth.

PMID- 26289509
TI  - Analyses of 1100 supernumerary teeth in a nonsyndromic Turkish population: A
      retrospective multicenter study.
AB  - PURPOSE: The aim of this study was to analyze the clinical and radiological
      features of supernumerary teeth (ST), record the related complications, and
      discuss different forms of treatment. MATERIALS AND METHODS: A total of 111,293
      patients were examined over a 3-year period. The patients' ages and genders, in
      addition to the number, morphology, location, position, shape, developmental
      stage, and eruption status of ST and associated complications, were recorded.
      RESULTS: Among the 111,293 patients, there were 851 (0.76%) patients with 1100
      ST. Of these patients, 478 (56.2%) were males, and 373 (43.8%) were females, with
      a mean age of 22.71. Most of the 1100 ST were located in the maxilla, 437
      (39.72%) were a conical shape, with 82.81% of these including a fully developed
      tooth. A mesiodens was the most common type of supernumerary tooth (n=284,
      33.37%), followed by distomolars (n=204, 23.97%) and parapremolars (n=146,
      17.16%). Among the 1100 ST, 422 (38.36%) were associated with complications.
      CONCLUSIONS: No previous studies in the literature have examined in detail so
      many cases with ST. The demographic profile of the patients with ST presented
      herein provides useful additional epidemiological information.

PMID- 26289510
TI  - Assessment of the biocompatibility of mineral trioxide aggregate, bioaggregate,
      and biodentine in the subcutaneous tissue of rats.
AB  - OBJECTIVE: The objective of this study was to evaluate the tissue inflammation
      caused by three endodontic repair materials. MATERIALS AND METHODS: The materials
      included micro mega-mineral trioxide aggregate (MM-MTA), bioaggregate (BA), and
      biodentine (BD), which were implanted into the subcutaneous tissue of rats. The
      tissue samples for histological examination were prepared. The infiltration of
      lymphocytes and macrophages into the tissue was examined to assess the
      inflammatory response. RESULTS: Lymphocyte infiltration: A significant increase
      was detected in the MM-MTA and BA groups on the 7th and 14th days as compared
      with the control (7th day P=0.0001, 14th day P=0.0176). There was no difference
      between the groups on the 45th day (P=0.1730). Lymphocyte infiltration had
      decreased over time in all groups. Macrophage infiltration: There was a
      significant increase by the 7th day in the test groups as compared to the control
      group (P=0.007). However, there was no difference between the experimental groups
      on the 14th (P=0.2708) and 45th (P=0.1291) days. CONCLUSION: While MM-MTA and BA
      showed a similar biocompatibility, BD was more biocompatible than MM-MTA and BA
      in the 1 st week of the experiment. However, there was no difference between the
      materials at the end of the 45th day. MM-MTA, BA, and BD can be considered
      suitable endodontic repair materials.

PMID- 26289511
TI  - Maternal risk factors for singleton preterm births and survival at the University
      of Nigeria Teaching Hospital, Enugu, Nigeria.
AB  - CONTEXT: Risk factors for and survival of singleton preterm births may vary
      according to geographical locations because of socioeconomic differences and
      lifestyle. AIMS: The aim was to describe maternal risk factors and survival-to
      discharge rate for singleton preterm births at the University of Nigeria Teaching
      Hospital and determine the relationship between maternal risk factors and the
      survival of singleton preterm babies. SUBJECTS AND METHODS: A comparative
      retrospective review of singleton preterm and term births from January 2009 to
      December 2013 was carried out. Statistical analysis involved descriptive and
      inferential statistics at 95% level of confidence using the Statistical Package
      for Social Sciences (SPSS) version 15 for Windows. P<=0.05 was considered
      significant. RESULTS: A total of 784 births including 392 singleton preterm
      births (aged 26-36+6) and 392 singleton term births were studied. The mean age of
      mothers who delivered singleton preterm babies did not differ significantly from
      that of mothers who delivered singleton term babies (30.2+/-4.9 years vs. 30.8+/
      4.7; P=0.06). Lack of antenatal care (adjusted odds ratio [aOR]=2.63; 95%
      confidence interval [CI] 1.92, 6.07), Previous preterm birth (aOR=5.06; 95% CI:
      2.66, 9.12), having pregnancy complications including antepartum hemorrhage,
      preeclampsia/eclampsia or premature rupture of membranes (aOR=5.12; 95% CI: 2.4,
      11.8), being unmarried (aOR=2.41; 1.56, 3.71) and nulliparity (aOR=2.08, 95% CI:
      1.22, 4.91) were independent risk factors for singleton preterm births. The
      average survival-to-discharge rate for preterm babies during the period was
      38.4%. The mean duration of admission for singleton preterm babies was 16+/-5.8
      days (range: 2-75 days). Whereas survival was dependent on, gestational age at
      birth (P<0.001) and mode of delivery (P=0.01), it was not dependent on maternal
      risk factors of parity, marital status, complications of pregnancy, and antenatal
      care. CONCLUSIONS: There was a low rate of survival of singleton preterm babies
      at the study center and survival was dependent on gestational age at birth and
      mode of delivery, but not on maternal sociodemographic risk factors for singleton
      preterm births. Active collaboration between the obstetrician and the
      neonatologist in deciding when and how to deliver these babies may provide
      improved chances of survival.

PMID- 26289512
TI  - Oral hygiene and oral flora evaluation in psychiatric patients in nursing homes
      in Turkey.
AB  - CONTEXT: The World Health Organization has stated that psychiatric patients are a
      group of people who have oral and dental illnesses. AIMS: The aims of this study
      were to document the oral hygiene of individuals with chronic psychiatric
      illness, to determine the extraoral and intraoral findings, to detect the
      dominant microorganisms in oral flora, and to inform clinicians of these
      findings. SETTINGS AND DESIGN: The study included 100 patients (69 men and 31
      women) with different psychiatric illnesses living in a nursing home. They were
      19-96 years old (median, 48 years). SUBJECTS AND METHODS: The participants
      completed a questionnaire about patients' oral health. They underwent extraoral
      and intraoral examinations. Two swab samples were obtained from the oral mucosa
      of these patients. Gram preparations were analyzed for leukocytes, bacteria, and
      yeast. STATISTICAL ANALYSIS USED: Chi-square test and z-test were used. RESULTS:
      All patients (100%) had the necessary equipment for oral hygiene; however, many
      (43%) patients had poor oral hygiene. There was a high prevalence of xerostomia
      (56%) and fissured tongue (61.4%) (among other tongue anomalies). The most
      commonly isolated microorganisms were coagulase-negative Staphylococcus0 (35.9%),
      Streptococcus spp. (30.3%), nondiphtheroid Bacilli (16.9%), Staphylococcus aureus
      (2.3%), Candida spp. (11.8%), and Gram-negative Bacilli (2.8%). CONCLUSIONS: The
      oral hygiene of most patients was insufficient. The presence of Gram-negative
      Bacilli growth in the oral flora can be explained by poor hand hygiene. These
      findings suggest that it is useful to educate individuals about oral hygiene and
      hand hygiene and to inform the staff and families about this issue.

PMID- 26289513
TI  - Nutritional status and laboratory parameters among internal medicine inpatients.
AB  - BACKGROUND: Malnutrition is a clinical state resulting in prolonged hospital
      stay, increase in severity of infections and poor wound healing. AIMS: Our aim
      was to investigate the prevalence and etiologic factors of malnutrition in
      medical inpatients. STUDY DESIGN: A total of 290 consecutively admitted internal
      medicine patients from February to May 2012 were included. On admission,
      demographic data, anthropometric measurements, laboratory parameters and
      nutritional screening test results were recorded. METHODS: Nutritional risk score
      2002 for patients under 65 years old, mini nutritional assessment for older
      patients and subjective global assessment (SGA) tests performed. Relation of
      demographic characteristics, laboratory parameters, weight and body mass index
      (BMI) with nutritional status were evaluated. RESULTS: Mean age was 61+/-17
      years; 145 patients were male. Among 160 patients<65 years old, 34 were in
      malnutrition (21%), 41 (26%) were under risk of malnutrition and 85 (53%) were
      normal. When they were divided into three groups according to SGA, we found
      significant difference in hemoglobin, low density lipoprotein (LDL), high density
      lipoprotein, cholesterol, triglyceride, albumin and protein, weight and BMI.
      Among 130 patients over 65 years old, 47 patients (37%) were in malnutrition, 41
      (31%) were under risk of malnutrition and 42 (32%) were normal. There was
      significant difference in LDL, cholesterol, albumin, protein, weight and BMI
      between three groups; each 1 g/dl decrease in serum albumin and age older than 65
      years old increased malnutrition risk 5.21 and 1.97 times, respectively.
      CONCLUSION: Malnutrition risk is high among internal medicine inpatients and risk
      seems to be higher among older patients. Nutritional screening of geriatric
      patients, close follow-up and providing earlier health care would contribute
      rehabilitation of chronic diseases and decrease re-admissions.

PMID- 26289514
TI  - Effect of Hibiscus sabdariffaon blood pressure and electrolyte profile of mild to
      moderate hypertensive Nigerians: A comparative study with hydrochlorothiazide.
AB  - BACKGROUND: Hibiscus sabdariffa (HS) is widely consumed in Nigeria as a
      refreshing beverage and also as an antihypertensive agent. Since three decades
      ago when its antihypertensive activities were reported in several animal
      experiments, its consumption has greatly increased. AIM: The aim of this study is
      to investigate the effect of HS consumption on blood pressure (BP) and
      electrolytes of mild to moderate hypertensive Nigerians and compare it with that
      of hydrochlorothiazide (HCTZ), a diuretic widely used as first-line
      antihypertensive drug. SUBJECTS AND METHODS: Eighty newly diagnosed, but
      untreated mild to moderate hypertensive subjects attending Medical Out-Patients
      clinic of Enugu State University Teaching Hospital, Enugu, were recruited for the
      study. They were randomly divided into three groups: A, B and C. Those in Groups
      A were given placebo; those in Group B took HCTZ while those in Group C were
      given HS. Treatment lasted for 4 weeks. BP, serum, and urine electrolytes were
      measured at baseline, weekly during treatment and 1 week after withdrawal of
      treatment. RESULTS: At the end of treatment, both HCTZ and HS significantly
      (P<0.001) reduced systolic BP, diastolic BP, mean arterial pressure and serum Na+
      compared to placebo. When compared to each other, HCTZ significantly (P<0.001)
      reduced serum Na+ and Cl- compared to HS and significantly (P<0.001) increased K+
      and Cl- output in urine. After withdrawal of treatment, the fall in BP and serum
      Na+ in HS group were significant compared to HCTZ where they returned to baseline
      values. No side effect was reported during the study. CONCLUSION: HS was a more
      effective antihypertensive agent than HCTZ in mild to moderate hypertensive
      Nigerians and did not cause electrolyte imbalance. HS showed longer duration of
      action compared to HCTZ and reduction in serum Na+ may be another
      antihypertensive mechanism of action of HS.

PMID- 26289515
TI  - Appraisal of timing for oral glucose tolerance testing in relation to risk
      factors for gestational diabetes mellitus in pregnant women in a Nigerian
      Teaching Hospital.
AB  - OBJECTIVE: We investigated the pattern of common risk factors present in women
      undergoing oral glucose tolerance test (OGTT) in our center and to determine
      their relationship with time of presentation for the test. MATERIALS AND METHODS:
      The records of women referred to the metabolic clinic for OGTT over a 1-year
      period were reviewed. Data available for retrieval included age, gravidity and
      gestational age, weight, and risk factors for gestational diabetes mellitus
      (GDM). RESULTS: Two hundred and fifty-three (253) pregnant women form the subject
      of this study. Thirty-five (13.8%) of the study population had GDM by WHO
      criteria. Approximately, 10% of the women were tested before 24 weeks and 87.6%
      of the women had at least one of the common risk factors as indication for
      testing. The most frequent indications were a history of previous macrosomic baby
      77 (30.4%) and maternal obesity 61 (24.1%). Among the indications for OGTT, only
      a history of previous intrauterine fetal death was significantly associated with
      testing before 24 weeks of gestation. CONCLUSION: Early screening for GDM is not
      common in our environment. The presence of risk factors for GDM did not prompt
      early screening. Public enlightenment on the risk factors for GDM and the need
      for early screening should be vigorously pursued particularly for women at risk
      for GDM.

PMID- 26289516
TI  - Pattern of admission and outcome of patients admitted into the Intensive Care
      Unit of University of Nigeria Teaching Hospital Enugu: A 5-year review.
AB  - OBJECTIVE: The objective was to determine the pattern of admission and outcome of
      patients in the Intensive Care Unit (ICU) of University of Nigeria Teaching
      Hospital (UNTH), Enugu, Nigeria. MATERIALS AND METHODS: A retrospective review of
      all patients admitted into the general ICU at UNTH from 2008 to 2012. Data were
      collected from the ICU admission and discharge registers, and data analysis was
      done using Microsoft Excel 2007. RESULTS: A total of 766 patients were admitted
      during the period, consisting of 501 (65.4%) males and 265 (34.6%) females. Ages
      ranged from 1-day to 89 years with a mean age of 38.2+/-18.2 years. The most
      common cases admitted were neurosurgical patients of which there were 316
      (41.2%). Patients admitted as a result of critical incidents in anesthesia formed
      the lowest number of cases admitted 10 (1.3%). Of the 316 neurosurgical cases,
      224 (70.9%) were due to severe traumatic brain injury (TBI). An overall admission
      of 92.4% (207) was for severe TBI due to motor-vehicular accident (MVA). The
      average length of stay was <24 h to 72 days with a mean of 4.9+/-3.2 days. A
      total of 16.7% (128) patients received invasive mechanical ventilation during
      their stay in ICU. Only 15% (34 patients) of all the cases of severe TBI patients
      received invasive mechanical ventilation. Mortality rate was 34.6% in this study.
      CONCLUSION: The highest number of admissions into the ICU was for severe TBI
      following MVA. Developing a viable trauma team and separately equipped
      neurosurgical ICU with adequately trained and motivated staff will help improve
      the outcome of patients.

PMID- 26289517
TI  - Point of care testing: Knowledge and utilization amongst Doctors in Government
      hospitals in Edo State, Nigeria.
AB  - OBJECTIVE: The study assessed the knowledge and utilization of point of care
      testing (POCT) amongst doctors in two health facilities in Edo State, Nigeria.
      METHODS: A descriptive cross-sectional study was carried out using a multistage
      sampling technique. Data were collected from 174 doctors in both centers using a
      25 item structured questionnaire which was analyzed using SPSS version 20.0.
      RESULT: The mean age of respondents was 31.26+/-2.14 years with 120 (69.0%) males
      and 54 (31.0%) females (male: female=2.2:1). Knowledge of POCT and utilization of
      POCT devices was good in 50.6% and 32.2% of respondents respectively. Utilization
      of POCT correlated significantly with knowledge of POCT (r=0.67, P<0.001) and
      availability of POCT devices (r=0.43, P<0.001). There was statistically
      significant association between utilization of POCT devices and Hospital
      (chi2=9.95, P=0.002); job designation (chi2=10.03, P=0.018) and availability of
      POCT devices (chi2=6.80, P=0.001). However, no statistically significant
      relationship was found between utilization of POCT devices and sex (chi2=0.23,
      P=0.629). CONCLUSION: Promotion of POCT's utilization with regulation, training
      of doctors and establishment of regulatory framework/assessment teams will help
      improve healthcare services and achieve more beneficial outcomes. That way, POCT
      that is faster could be better.

PMID- 26289518
TI  - Mini-mental state exam versus Montreal Cognitive Assessment in patients with
      diabetic retinopathy.
AB  - BACKGROUND: Mini-mental state exam (MMSE) was used several times but no study has
      examined cognition on the Montreal Cognitive Assessment (MoCA) in diabetes and
      diabetic retinopathy (DR). In this study, we compared MMSE with MoCA in patients
      with DR and searched for an association between the severity of DR and cognitive
      impairment (CI). METHODS: This cross-sectional study comprised 120 consecutive
      patients with diabetes. Patients were divided into four groups as no DR, mild DR,
      severe nonproliferative DR (PDR) and PDR. Each group consisted 30 inviduals. CI
      was assessed using the MMSE and MoCA. RESULTS: The number of subjects with a
      score>21 were significantly lower on the MoCA than on the MMSE between groups
      (all P<0.05). The mean MoCA score was significantly lower than the MMSE score
      (P<0.001) There was a linear association between the grade of DR and a score<21
      on both tests, CONCLUSION: MoCA provides more insight into the cognitive function
      in DR.

PMID- 26289519
TI  - Self-reported physical activity among health care professionals in South-West
      Nigeria.
AB  - INTRODUCTION: Physical activity (PA) is a key requirement for maintaining good
      health. There is growing evidence of declining PA worldwide. Physical inactivity
      is linked with the global obesity pandemic and increasing burden of
      noncommunicable diseases (NCDs) in developing countries. A barrier to PA
      counseling by health care providers (HCPs) is personal PA habits. Information
      regarding PA among HCPs in Nigeria is limited. We aimed to determine the adequacy
      and predictors of PA among HCPs of a tertiary health care facility in Lagos,
      Nigeria. METHODS: A cross-sectional study was carried out with the International
      Physical Activity Questionnaire-Short Form (IPAQ-SF). Using the World Health
      Organization (WHO) guideline, PA was categorized as adequate or inadequate.
      Predictors of PA were explored with multivariate logistic regression. RESULTS: A
      total of 300 HCPs were recruited, comprising 47.7% doctors and dentists, 43.3%
      nurses and 9.0% other HCPs. Mean age was 39.9 (9.0 years), 79.2%, 9.7% and 11.1%
      of the HCPs had low, moderate or high PA levels respectively. Thus, only 20.8%
      had adequate PA. 71.3% had body mass index (BMI) above the recommended value. BMI
      of >=25 kg/m2 was associated with inadequate PA (Adjusted Odds Ratio
      2.1,P=0.018). CONCLUSION: Majority of the HCPs had inadequate PA levels according
      to WHO guidelines. BMI>=25 kg/m2 was associated with inadequate physical
      inactivity. The low level of PA implies that these HCPs are at risk for NCDs.
      This will have a negative impact on availability of human resource for health.
      There is an urgent need to establish programs to increase PA among HCPs.

PMID- 26289520
TI  - Comparison of the efficacy of tenofovir and entecavir for the treatment of
      nucleos(t) ide-naive patients with chronic hepatitis B.
AB  - BACKGROUND: An important goal in the treatment of chronic hepatitis B virus (HBV)
      infection is to prevent hepatocellular carcinoma and liver cirrhosis by
      suppressing HBV replication. Tenofovir and entecavir are effective viral
      suppression compounds. However, comparative data is scant, especially in Korea.
      This study compared tenofovir and entecavir concerning efficiencies and side
      effects. MATERIALS AND METHODS: We retrospectively reviewed data of nucleos (t)
      ide-naive patients with chronic HBV infection. Independent variables reflecting
      virological response were evaluated, and the decline in serum HBV DNA levels, and
      side effects between tenofovir-and entecavir-treated patients were compared at
      treatment week 12, 24, and 48. RESULTS: At the end of 48 weeks, there was no
      statistical difference in the induction of undetectable levels of HBV DNA between
      the entecavir (82.5%) and tenofovir (69.2%) groups. Entecavir was more effective
      in reducing serum HBV DNA levels at 24 weeks of treatment (serum HBV DNA decline
      of 5.53 and 4.95 log10 units for entecavir and tenofovir, respectively; P=0.044),
      but the rate of decline was similar at other weeks. There was no difference
      between the two groups in terms of side effects and discontinuance of treatment
      due to side effects. CONCLUSIONS: Tenofovir is not significantly different from
      entecavir in virologic response and tolerability in the treatment of chronic HBV.

PMID- 26289521
TI  - Evaluation of the amount of apically extruded debris during retreatment of root
      canals filled by different obturation techniques.
AB  - OBJECTIVE: To evaluate the amount of apically extruded debris during retreatment
      (with or without solvent) of root canals filled by two obturation techniques.
      MATERIALS AND METHODS: Forty-eight root canals were prepared using ProTaper
      Universal F3 and filled with Gutta-percha and AH 26 sealer using single cone or
      lateral condensation techniques. The root canal fillings were removed using
      ProTaper Universal Retreatment system with or without solvent, and the canals
      were further prepared with ProTaper F4. The operating time was measured. The
      debris extruded was collected into preweighed Eppendorf tubes. The dry weight of
      the extruded debris was calculated by subtracting the weight of the empty tube
      from that of the tube containing debris. Statistical analysis was performed with
      two-way analysis of variance test, with Bonferroni correction at a 95% confidence
      level. RESULTS: There was no statistically significant difference in the amount
      of extruded debris between the two obturation techniques (P=0.332). The mean
      amount of debris was higher in the nonsolvent groups than the solvent groups,
      particularly with the single cone technique (P=0.013). There was a significant
      difference between groups with regard to the retreatment time (P<0.001). Gutta
      percha removal took less time in the single cone group than in the lateral
      condensation group (P<0.001). Gutta-percha removal in the nonsolvent groups took
      significantly less time than that in the solvent groups (P<0.001). CONCLUSIONS:
      The amounts of apically extruded debris were similar in both obturation
      techniques. A greater amount of apically extruded debris was observed in the
      nonsolvent groups than the solvent groups.

PMID- 26289522
TI  - Stroke risk factors among participants of a world stroke day awareness program in
      South-Western Nigeria.
AB  - INTRODUCTION: Stroke is a major cause of death and disability in population
      across the world. Hypertension is the most common stroke risk factor globally as
      well as in the Nigerian population, however other modifiable risk factors such as
      obesity are becoming increasingly prevalent due to unhealthy diets and sedentary
      lifestyle. MATERIALS AND METHODS: We screened 224 volunteers from Ile-Ife during
      the 2011 and 2012 world stroke day commemorative activities. Blood pressures (BP)
      were measured and body mass index (BMI) was determined from weight and height
      measurements. The data from 40 (18%) were incomplete and were excluded from
      further analysis. RESULTS: The 184 subjects eligible for analysis comprised 85
      males (46.2%) and 99 females (53.8%), with a male to female ratio of 0.85:1.
      Their ages ranged from 16 to 95 years (mean, 53+/-16 years). 25% of the study
      population had stage 1 or 2 hypertension (mean systolic blood pressure: 127+/-27
      mmHg, mean diastolic blood pressure: 78+/-16 mmHg), while 34.8% and 14.7% were
      overweight and obese, respectively (mean BMI: 25.8+/-5.0 kg/m2). CONCLUSION:
      Stroke risk factors such as hypertension and obesity were common among the
      participants of the world stroke day awareness program in an urban area of
      Nigeria. Community screening and modification of these risk factors should be
      intensified in order to reduce stroke morbidity and mortality.

PMID- 26289523
TI  - Is there a relationship between the diameter of the inferior vena cava and
      hemodynamic parameters in critically ill patients?
AB  - INTRODUCTION: The early detection of critically ill patients together with the
      rapid initiation of effective treatment in emergency departments(ED) increase the
      survival rates. AIM: This study investigated whether a correlation exists between
      haemodynamic parameters of critically ill patients and the diameter of the
      inferior vena cava (IVC). MATERIALS AND METHODS: A cross-sectional study was
      performed included patients aged >=18 years with an unstable haemodynamic and/or
      respiratory status who were referred to the ED for non-traumatic issues. IVC
      diameters were measured by ultrasound (US) and then central venous pressures
      (CVP) were measured. Anteroposterior (AP) and mediolateral (ML) diameters of the
      IVC, both in the inspirium (IAP, IML) and expirium (EAP, EML), were measured by
      US. RESULTS: 102 patients were evaluated with a median age of 59. The
      relationship between the diameters of IVC and CVP was evaluated and significant
      correlation was found in IAP, EAP according to CVP values (p<0.001). ROC analyses
      were performed and significant relationship was found between the EAP diameter
      with haemoglobin (Hmg), haemotocrit (Hct), and central venous oxygen saturation
      (ScvO2) and also significant correlation was detected between the IAP diameter
      and white blood cell (WBC). DISCUSSION: We detected significant correlation
      between the CVP and the IVC diameter in our study compatible with recent studies
      besides, significant correlation was found between the diameter of the IVC and
      CVP values as well as between the EAP diameter and Hmg, Hct, ScvO2 levels.
      CONCLUSION: Measurement of IVC diameters, especially EAP may be useful at the
      monitoring of critically ill patients in ED.

PMID- 26289525
TI  - Seroprevalence of hepatitis B virus infection among pregnant women at the
      antenatal booking clinic of a Tertiary Hospital in Lagos Nigeria.
AB  - OBJECTIVES: The objectives were to determine the seroprevalence of hepatitis B
      virus (HBV) infection and assess the major risk factors among Nigerian pregnant
      women. SUBJECTS AND METHODS: This was a cross-sectional descriptive study carried
      out among pregnant women at the antenatal clinic of a Tertiary Hospital in Lagos,
      Nigeria. A total number of 150 consenting pregnant women were selected for the
      study. A structured pretested interviewer-administered questionnaire was used for
      the data collection. Sera were collected and tested for hepatitis B surface
      antigen (HBsAg) and hepatitis B e antigen (HBeAg). RESULTS: Of the 150 women
      screened during the study, 11 (7.3%) were seropositive for HBsAg. Of these 11
      women, 4 (36.4%) were also positive for HBeAg. There was no statistically
      significant difference in the mean ages of participants who were seropositive for
      HBsAg and those who were negative for the virus (P=0.888). There were
      statistically significant differences in the seroprevalence of HBsAg recorded
      among respondents with previous surgery (odd ratio [OR]-2.97; 95% confidence
      interval [CI]-1.08-16.67; P=0.046), previously affected sibling or spouse (OR
      5.03; 95% CI-1.11-25.27; P=0.001) and those with two or more lifetime sexual
      partners (OR-4.11; 95% CI-2.85-9.22; P=0.024). CONCLUSION: The sero-prevalence
      rate of HBV infection and also its infectivity is high in Lagos, Nigeria. These
      findings thus support the need for a nationwide policy of routine and widespread
      HBV screening among pregnant women.

PMID- 26289524
TI  - Effects of ozone and photo-activated disinfection against Enterococcus faecalis
      biofilms in vitro.
AB  - OBJECTIVES: The purpose of this study was to compare the antibacterial effects of
      gaseous ozone (O3) and photo-activated disinfection (PAD) methods against
      Enterococcus faecalis (E. faecalis) biofilms. MATERIALS AND METHODS: Sixty-five
      human mandibular premolars with straight root canals were selected. After root
      canal preparation, the samples were sterilized and placed into eppendorf tubes
      with 1 mL brain heart infusion broth containing 1.5*10(8) colony-forming units
      (CFUs)/mL of E. faecalis. The contaminated samples were then divided into four
      groups (n=15) according to the disinfection method used: Group 1, Saline
      (positive control); Group 2, NaOCl (negative control); Group 3, Gaseous O3; and
      Group 4, PAD. Three non-contaminated teeth were used to control the infection and
      sterilization process. The CFUs were counted and the data were analyzed
      statistically. RESULTS: There was a statistically significant difference between
      the experimental and control groups (P<0.05). The saline group had the highest
      number of remaining microorganisms. Complete sterilization was achieved in the
      2.5% NaOCl group. There were no statistically differences between PAD and gaseous
      O3 (P>0.05). CONCLUSION: Both PAD and gaseous O3 have a significant antibacterial
      effect on infected root canals. However, 2.5% NaOCl was superior in terms of its
      antimicrobial abilities compared with the other disinfection procedures.

PMID- 26289526
TI  - Laparoscopic supracervical hysterectomy and uterine morcellation: A case report
      from Asokoro District Hospital, Abuja, Nigeria.
AB  - Advanced gynecological laparoscopic surgery is an evolving subspecialty that
      requires specialized skills, expertise and equipment. This is more challenging
      and daunting, especially in sub Saharan Africa. Laparoscopic supracervical
      hysterectomy (LSCH) is an advanced gynecological procedure that has hitherto been
      seen as difficult because of the big size uteri seen in Nigerian women. We
      present thefirst LSCH and uterine morcellation done in Nigeria in a 45-year-old
      multipara on account of symptomatic uterine fibroid of 16 weeks size, at the
      Asokoro District Hospital, Abuja. Nigeria. She fared well postoperatively and
      highly satisfied with the procedure at the gynecological clinic review. Our case
      report has demonstrated clearly that the uterine size is not a limitation to
      laparoscopic hysterectomy. With proper port placement and adequate skills, LSCH
      of big size uteri, which is typical in sub Saharan Africa, can be safely
      achieved. We, therefore, recommend capacity building of Gynaecologists and peri
      operative nurses in the field of minimal access surgery and improvement in the
      equipment in our various facilities to the modern standard. 

PMID- 26289527
TI  - Chronic myeloid leukemia presented with priapism: Effective management with
      prompt leukapheresis.
AB  - Priapism is a painful medical condition in which the erect penis does not return
      to its flaccid state, despite the absence of both physical and psychological
      stimulation, within 4 h. Priapism is considered a medical emergency, which should
      receive proper treatment by a qualified medical practitioner. Treatment initially
      involves conservative measures, such as corporeal aspiration and irrigation with
      saline or dilute phenylephrine. If this fails, embolization or surgical shunting
      may be required. Priapism is more commonly associated with sickle cell
      hemoglobinopathy. However, hyperviscosity resulting from leukemia is a rare cause
      of priapism. We report a case of a 19-year-old man with an 18-h history of
      priapism secondary to undiagnosed chronic myeloid leukemia. We discuss the method
      of leukapheresis (mechanical white cell depletion) to reduce viscosity. 

PMID- 26289528
TI  - 'Weight control, Alcohol reduction, Smoking cessation, Health promotion, Exercise
      and Diet (WASHED)': A mnemonic for lifestyle modification in obesity.

PMID- 26289529
TI  - Systematic review of the quality of life issues associated with anal cancer and
      its treatment with radiochemotherapy.
AB  - PURPOSE: Radiochemotherapy is the standard of care for the treatment of anal
      carcinoma achieving good loco-regional control and sphincter preservation. This
      approach is however associated with acute and late toxicities including
      haematological, skin, bowel function and genito-urinary complications. This paper
      systematically reviews studies addressing the quality of life (QoL) implications
      of anal cancer and radiochemotherapy. The paper also evaluates how QoL is
      assessed in anal cancer. METHODS: Medline, EMBASE, CINAHL, PsycInfo, Web of
      Science and the Cochrane Library were searched for publications (1996-2014)
      reporting the effects on patients of anal cancer and radiochemotherapy. RESULTS:
      Of the 152 papers reporting treatment-related effects on patients, only 11
      provided a formal assessment of QoL. In the absence of an anal cancer-specific
      measure, QoL was assessed using generic cancer instruments such as the core EORTC
      quality of life questionnaire (EORTC QLQ-C30) or colorectal cancer tools such as
      the EORTC QLQ-CR29. Bowel function, particularly diarrhoea, and sexual problems
      were the most commonly reported QoL concerns. The review of QoL issues of anal
      cancer patients treated with radiochemotherapy is limited by the QoL assessment
      measures used. It is argued that certain treatment-related toxicities, for
      example skin-induced radiation problems, are overlooked or inadequately
      represented in existing measures. CONCLUSIONS: This review emphasises the need to
      develop an anal cancer-specific QoL measure and to incorporate QoL as an outcome
      of future trials in anal cancer. The results of this review are informative to
      clinicians and patients in terms of treatment decision-making.

PMID- 26289530
TI  - Xylaria hypoxylon Lectin as Adjuvant Elicited Tfh Cell Responses.
AB  - Foot-and-mouth disease (FMD) caused by FMD virus (FMDV) is a major health and
      economic problem in the farming industry. Vaccination of livestock against this
      highly infectious viral disease is crucial, and inactivated FMD vaccine has been
      effective at controlling infection. However, accumulated data show that the
      inactivated vaccine generates weak immune responses and that the oil formulation
      results in undesirable side effects. Mushroom lectins have recently been shown to
      display adjuvant effects when incorporated into DNA vaccines. In this study, to
      enhance the cellular immune response of FMDV antigen (146S), C57BL/6 mice were
      immunized with 146S combined with Xylaria hypoxylon lectin (XHL). The oil
      formulation (146S/Oil) was served as control group. Strong humoral immune
      responses were elicited in mice immunized with 146S/XHL as shown by high 146S
      antigen-specific IgG levels, and also in 146S/Oil group. Interestingly, XHL in
      conjunction with inactivated FMD vaccine activated strong Th1 and Tc1 cell
      responses, especially Tfh cell responses, in immunized mice. XHL stimulated
      dendritic cell maturation by upregulating expression of major histocompatibility
      complex II (MHCII) molecules and co-stimulatory molecules CD40 and CD86 in
      immunized mice. No XHL-specific IgG or inflammatory factors were detected
      indicating the safety of XHL as an adjuvant. Taken together, these results
      suggest the effectiveness of XHL at inducing cellular immune responses and
      therefore confirm its suitability as an adjuvant for inactivated FMD vaccine.

PMID- 26289532
TI  - Long pulse Alexandrite laser for recalcitrant viral warts on the hands.

PMID- 26289531
TI  - Involvement of Notch signaling in early chick ovarian follicle development.
AB  - The formation of primordial follicles is a crucial process in the establishment
      of follicle pools required for the female's reproductive life span. For laying
      hens, ample follicles are a prerequisite for high laying performance. Notch
      signaling plays critical roles in germ cell cysts breakdown and in the formation
      of primordial follicles. Here, we investigated the role of Notch signaling in the
      ovarian development of post-hatch chicks. Results showed that around post-hatch
      day 4 (H4), the germ cell cysts broke apart, oocytes became surrounded by
      squamous pregranulosa cells, and the primordial follicles were then formed.
      Subsequently, we detected the expression of Notch signaling-related genes
      including Notch receptors (Notch1, 2), ligands (Jag1, 2 and Dll1, 4), and target
      genes (Hes1, Hey1). These genes all showed expression at H4 and some of these
      genes were up-regulated during primordial follicle formation. To evaluate the
      Notch signaling requirement for early follicular development, we adopted an in
      vitro ovary culture system. Suppression of Notch signaling by gamma-secretase
      inhibitor induced a decrease of primordial follicles and an increase of germ
      cells in cysts. Attenuating Notch signaling also inhibited the
      phosphatidylinositol 3-kinase/protein kinase B pathways and suppressed cadherin
      expression. These results suggest that Notch signaling is endowed with an
      indispensable role in primordial follicle formation in post-hatch chicks.

PMID- 26289534
TI  - Prioritization of rheumatoid arthritis risk subpathways based on global immune
      subpathway interaction network and random walk strategy.
AB  - The initiation and development of rheumatoid arthritis (RA) is closely related to
      mutual dysfunction of multiple pathways. Furthermore, some similar molecular
      mechanisms are shared between RA and other immune diseases. Therefore it is vital
      to reveal the molecular mechanism of RA through searching for subpathways of
      immune diseases and investigating the crosstalk effect among subpathways. Here we
      exploited an integrated approach combining both construction of a subpathway
      subpathway interaction network and a random walk strategy to prioritize RA risk
      subpathways. Our research can be divided into three parts: (1) acquisition of
      risk genes and identification of risk subpathways of 85 immune diseases by using
      subpathway-lenient distance similarity (subpathway-LDS) method; (2) construction
      of a global immune subpathway interaction (GISI) network with subpathways
      identified by subpathway-LDS; (3) optimization of RA risk subpathways by random
      walk strategy based on GISI network. The results showed that our method could
      effectively identify RA risk subpathways, such as MAPK signaling pathway,
      prostate cancer pathway and chemokine signaling pathway. The integrated strategy
      considering crosstalk between immune subpathways significantly improved the
      effect of risk subpathway identification. With the development of GWAS, our
      method will provide insight into exploring molecular mechanisms of immune
      diseases and might be a promising approach for studying other diseases. 

PMID- 26289533
TI  - Lack of infectivity of HBV in feces from patients with chronic hepatitis B virus
      infection, and infection using chimeric mice.
AB  - BACKGROUND: Body fluids such as saliva and tears from patients with hepatitis B
      virus (HBV) infection are known as infectious agents. The infectivity of feces
      from patients with HBV infection has not been established. The aim of this study
      was to determine whether feces from HBV carriers can be a source of HBV
      infection. METHODS: Thirty-three children and 17 adults (ages 0-49 years, median
      age 13 years) who were chronically infected with HBV were enrolled. The levels of
      HBV DNA in the feces from these patients were quantified by real-time PCR, and
      the levels of fecal HBsAg were measured. Isolated human hepatocytes from chimeric
      mice with humanized livers were co-cultured with serum, tears and feces from the
      HBV carriers. Four chimeric mice were inoculated intravenously with sterilized
      feces from HBV carriers. RESULTS: HBV DNA was detected in the feces of 37 (74%)
      of the 50 patients. The fecal HBV DNA levels ranged from 2.8 to 8.4 log copies/mL
      (mean +/- SD  =  5.6 +/- 1.2 log copies/mL). A significant correlation was
      observed in the levels of HBV DNA between serum and feces (r  =  0.54, p < 0.05).
      Of the 13 HBV carries, 7 (54%) were positive for fecal HBsAg. The fecal HBsAg
      levels ranged from 0.06 to 1.0 IU/mL (median 0.28 IU/mL). Immunogold electron
      microscopy showed Dane particles in feces. HBV DNA was detected in the human
      hepatocytes co-cultured with serum and tears, but not in those co-cultured with
      feces. HBV DNA was not detected in the serum of the chimeric mice after oral or
      intravenous inoculation with sterilized fecal samples, which contained 5 log
      copies/mL of HBV DNA levels. CONCLUSIONS: Although the positive rate of fecal HBV
      DNA was high, the fecal HBsAg levels were extremely low. The chimeric mice were
      not infected with HBV after oral or intravenous inoculation with sterilized fecal
      samples. Therefore, feces from HBV carriers seem not to serve as an infectious
      vehicle for the transmission of HBV.

PMID- 26289535
TI  - Evolutionary Design of Choline-Inducible and -Repressible T7-Based Induction
      Systems.
AB  - By assembly and evolutionary engineering of T7-phage-based transcriptional
      switches made from endogenous components of the bet operon on the Escherichia
      coli chromosome, genetic switches inducible by choline, a safe and inexpensive
      compound, were constructed. The functional plasticity of the BetI repressor was
      revealed by rapid and high-frequency identification of functional variants with
      various properties, including those with high stringency, high maximum expression
      level, and reversed phenotypes, from a pool of BetI mutants. The plasmid
      expression of BetI mutants resulted in the choline-inducible (Bet-ON) or choline
      repressible (Bet-OFF) switching of genes under the pT7/betO sequence at
      unprecedentedly high levels, while keeping the minimal leaky expression in
      uninduced conditions. 

PMID- 26289536
TI  - Sensitive determination of methadone in human serum and urine by dispersive
      liquid-liquid microextraction based on the solidification of a floating organic
      droplet followed by HPLC-UV.
AB  - Dispersive liquid-liquid microextraction based on solidification of floating
      organic droplet was developed for the extraction of methadone and determination
      by high-performance liquid chromatography with UV detection. In this method, no
      microsyringe or fiber is required to support the organic microdrop due to the
      usage of an organic solvent with a low density and appropriate melting point.
      Furthermore, the extractant droplet can be collected easily by solidifying it at
      low temperature. 1-Undecanol and methanol were chosen as extraction and disperser
      solvents, respectively. Parameters that influence extraction efficiency, i.e.
      volumes of extracting and dispersing solvents, pH, and salt effect, were
      optimized by using response surface methodology. Under optimal conditions,
      enrichment factor for methadone was 134 and 160 in serum and urine samples,
      respectively. The limit of detection was 3.34 ng/mmL in serum and 1.67 ng/mL in
      urine samples. Compared with the traditional dispersive liquid-liquid
      microextraction, the proposed method obtained lower limit of detection. Moreover,
      the solidification of floating organic solvent facilitated the phase transfer.
      And most importantly, it avoided using high-density and toxic solvents of
      traditional dispersive liquid-liquid microextraction method. The proposed method
      was successfully applied to the determination of methadone in serum and urine
      samples of an addicted individual under methadone therapy. 

PMID- 26289538
TI  - Andre T. Guay--In Memoriam.

PMID- 26289537
TI  - Monitoring of Microalgal Processes.
AB  - Process monitoring, which can be defined as the measurement of process variables
      with the smallest possible delay, is combined with process models to form the
      basis for successful process control. Minimizing the measurement delay leads
      inevitably to employing online, in situ sensors where possible, preferably using
      noninvasive measurement methods with stable, low-cost sensors. Microalgal
      processes have similarities to traditional bioprocesses but also have unique
      monitoring requirements. In general, variables to be monitored in microalgal
      processes can be categorized as physical, chemical, and biological, and they are
      measured in gaseous, liquid, and solid (biological) phases. Physical and chemical
      process variables can be usually monitored online using standard industrial
      sensors. The monitoring of biological process variables, however, relies mostly
      on sensors developed and validated using laboratory-scale systems or uses offline
      methods because of difficulties in developing suitable online sensors. Here, we
      review current technologies for online, in situ monitoring of all types of
      process parameters of microalgal cultivations, with a focus on monitoring of
      biological parameters. We discuss newly introduced methods for measuring
      biological parameters that could be possibly adapted for routine online use,
      should be preferably noninvasive, and are based on approaches that have been
      proven in other bioprocesses. New sensor types for measuring physicochemical
      parameters using optical methods or ion-specific field effect transistor (ISFET)
      sensors are also discussed. Reviewed methods with online implementation or online
      potential include measurement of irradiance, biomass concentration by optical
      density and image analysis, cell count, chlorophyll fluorescence, growth rate,
      lipid concentration by infrared spectrophotometry, dielectric scattering, and
      nuclear magnetic resonance. Future perspectives are discussed, especially in the
      field of image analysis using in situ microscopy, infrared spectrophotometry, and
      software sensor systems.

PMID- 26289539
TI  - Mindfulness Interventions for Treating Sexual Dysfunctions: the Gentle Science of
      Finding Focus in a Multitask World.

PMID- 26289540
TI  - Perspective: Regulatory Agencies' Changes to Testosterone Product Labeling.

PMID- 26289541
TI  - Correlates of Heterosexual Anal Intercourse among Women in the 2006-2010 National
      Survey of Family Growth.
AB  - INTRODUCTION: Heterosexual anal intercourse (HAI) is common among U.S. women.
      Receptive anal intercourse is a known risk factor for HIV, yet there is a paucity
      of data on HAI frequency and distribution in the United States. Condom use is
      lower with HAI vs. vaginal intercourse, but little is known regarding of
      correlates of HAI with and without condoms. AIMS: The aims of this study were to
      describe recent (past 12 months) and lifetime HAI among sexually active
      reproductive-aged U.S. women, and to characterize women who engage in HAI with
      and without condoms. METHODS: We analyzed a sample of 10,463 heterosexually
      active women aged 15-44 years for whom anal intercourse data were available in
      the 2006-2010 National Survey of Family Growth. MAIN OUTCOME MEASURES: Weighted
      bivariate and multivariable analyses were used to determine HAI prevalence and
      correlates. Primary outcomes were lifetime HAI, recent (last 12 months) HAI, and
      condom use at last HAI. RESULTS: In our sample, 13.2% of women had engaged in
      recent HAI and 36.3% in lifetime HAI. Women of all racial and ethnic backgrounds
      and religions reported recent anal intercourse. Condom use was more common at
      last vaginal intercourse than at last anal intercourse (28% vs. 16.4%, P <
      0.001). In multivariable analysis, correlates of recent HAI included: less
      frequent church attendance, younger age at first intercourse, multiple sexual
      partners, history of oral intercourse, history of unintended pregnancy, and
      treatment for sexually transmitted infections (all P < 0.05). Correlates of
      lifetime HAI were similar, with the addition of older age, higher education,
      higher income, and history of drug use (all P < 0.05). CONCLUSION: Women of all
      ages and ethnicities engage in HAI, at rates higher than providers might realize.
      Condom use is significantly lower for HAI vs. vaginal intercourse, putting these
      women at risk for acquisition of sexually transmitted infections.

PMID- 26289542
TI  - Editorial Comment on "A Randomized Prospective Double-Blind Comparison Trial of
      Clomiphene Citrate and Anastrozole in Raising Testosterone in Hypogonadal
      Infertile Men"--New Comparative Insight on Alternative Therapies for Low
      Testosterone in Subfertile Men.

PMID- 26289544
TI  - Same protocol, different continents, different patients: should we continue to
      conduct global heart failure trials?

PMID- 26289543
TI  - Serum Surfactant Protein D and Haptoglobin as Potential Biomarkers for
      Inflammatory Airway Disease in Horses.
AB  - BACKGROUND: The identification of serum biomarkers of lung inflammation would
      facilitate the diagnosis of inflammatory airway disease (IAD) in horses.
      HYPOTHESIS: Horses with IAD have higher serum concentrations of markers of
      inflammation compared to controls. ANIMALS: Twelve horses with IAD and 10 control
      horses. METHODS: This was a prospective case-control study. Blood and BALF were
      collected from horses with IAD and controls. Serum concentration of surfactant
      protein D (SP-D), haptoglobin, serum amyloid A (SAA) and of the soluble form of
      triggering receptor expressed on myeloid cells 1 (sTREM-1) was measured using
      commercial ELISA tests. RESULTS: Horses with IAD had higher serum concentration
      (log-transformed values) of SP-D (mean +/- SD: 1.773 +/- 0.51), haptoglobin
      (6.657 +/- 0.202) and SAA (0.128 +/- 0.396) compared to controls (0.942 +/-
      0.226, 6.38 +/- 0.22, -0.398 +/- 0.319, respectively; P < .01 for all).
      Furthermore, the concentrations of SP-D and haptoglobin combined allowed
      differentiating the 2 groups (IAD: 8.43 +/- 0.564, controls: 7.322 +/- 0.249, P <
      .0001) with a sensitivity and specificity of 100% when a cut-off of 7.70 (log
      value) was employed. CONCLUSIONS AND CLINICAL IMPORTANCE: Surfactant protein D
      and haptoglobin serum concentrations could be a diagnostic aid in IAD. Further
      studies are necessary to establish the specificity of our findings before they
      can be applied in everyday practice.

PMID- 26289545
TI  - Effect of chronic exposure to two components of Tritan copolyester on Daphnia
      magna, Moina macrocopa, and Oryzias latipes, and potential mechanisms of
      endocrine disruption using H295R cells.
AB  - Tritan copolyester is a novel plastic form from Eastman Company utilizing three
      main monomers, 1,4-cyclohexanedimethanol (CHDM), dimethyl terephthalate (DMT),
      and 2,2,4,4-tetramethyl-1,3-cyclobutanediol. Despite Tritan has been widely
      applied for plastic bottles, the effects of long-term exposure to these compounds
      have seldom been investigated. We investigated chronic effects and endocrine
      disruption potential of CHDM and terephthalic acid (TPA), main mammalian
      metabolite formed from DMT, using crustacean Daphnia magna and Moina macrocopa,
      and freshwater fish (Oryzias latipes). The effects on sex hormone balance and the
      associated mechanisms were also investigated by use of H295R cells. In chronic
      toxicity test, D. magna showed significant decrease in reproduction (number of
      young per female) after exposure to 10 mg/L TPA. In early life stage exposure
      using O. latipes, significant decrease of juvenile survival and weight were
      observed in fish exposed to 10 mg/L and >=1 mg/L CHDM, respectively. Expressions
      of vtg2 mRNA in fish exposed to CHDM and those of cyp19b, star, cyp17, and cyp19a
      mRNAs in fish exposed to TPA were significantly up-regulated. The results of
      H295R cell assay also showed that both chemicals at high concentrations could
      alter sex hormone production in steroidogenic pathway. The effective
      concentrations of the tested compounds were several orders of magnitude greater
      than the concentrations can be detected in ambient waters. Further in vivo and in
      vitro studies will be needed to investigate the effect of co-polymer on endocrine
      disruption.

PMID- 26289546
TI  - Recall is not necessary for verbal sequence learning.
AB  - The question of whether overt recall of to-be-remembered material accelerates
      learning is important in a wide range of real-world learning settings. In the
      case of verbal sequence learning, previous research has proposed that recall
      either is necessary for verbal sequence learning (Cohen & Johansson Journal of
      Verbal Learning and Verbal Behavior, 6, 139-143, 1967; Cunningham, Healy, &
      Williams Journal of Experimental Psychology: Learning, Memory, and Cognition, 10,
      575-597, 1984), or at least contributes significantly to it (Glass, Krejci, &
      Goldman Journal of Memory and Language, 28, 189-199, 1989; Oberauer & Meyer
      Memory, 17, 774-781, 2009). In contrast, here we show that the amount of previous
      spoken recall does not predict learning and is not necessary for it. We suggest
      that previous research may have underestimated participants' learning by using
      suboptimal performance measures, or by using manual or written recall. However,
      we show that the amount of spoken recall predicted how much interference from
      other to-be-remembered sequences would be observed. In fact, spoken recall
      mediated most of the error learning observed in the task. Our data support the
      view that the learning of overlapping auditory-verbal sequences is driven by
      learning the phonological representations and not the articulatory motor
      responses. However, spoken recall seems to reinforce already learned
      representations, whether they are correct or incorrect, thus contributing to a
      participant identifying a specific stimulus as either "learned" or "new" during
      the presentation phase. 

PMID- 26289547
TI  - [Multidrug-resistant tuberculosis: challenges of a global emergence].
AB  - Drug-resistant tuberculosis, in particular Multi-Drug Resistant (MDR-TB) is an
      increasing global concern and a major burden for some developing countries,
      especially the BRICS. It is assumed that every year roughly 350 000 new MDR-TB
      cases occur in the world, on average in 20.5% of TB patients that have been
      previously treated but also in 3.5% of persons that have never been on TB
      treatment before. The global distribution of cases is very heterogeneous and is
      now better understood thanks to a growing number of specific surveys and routine
      surveillance systems: incidence is much higher in southern Africa and in all
      countries formerly part of the USSR. Countries with weak health systems and
      previously inefficient TB control programs are highly vulnerable to MDR epidemics
      because program failures do help creating, maintaining and spreading resistances.
      Global response is slowly rolled out and diagnosis capacities are on the rise
      (mostly with genotypic methods) but adequate and successful treatment and care is
      still limited to a minority of global cases. From a public health perspective the
      MDR-TB growing epidemics will not be controlled merely by the introduction of few
      new antibiotics because it is also linked to patient's compliance and adequate
      case management supported by efficient TB program. In depth quality improvement
      will only be achieved after previous errors are thoroughly analyzed and boldly
      corrected.

PMID- 26289548
TI  - Parafoveal processing in reading Chinese sentences: Evidence from event-related
      brain potentials.
AB  - Natural reading involves the preprocessing of upcoming words, resulting in
      shorter fixations on words visible in the parafovea during preceding fixations.
      While this preview benefit is established in behavior, its brain-electric
      correlates have only recently been investigated. Using fixation-related
      potentials, an attenuation of the occipitotemporal N1 component for words that
      were parafoveally visible during preceding fixations has been demonstrated. In
      contrast, another study, using an RSVP paradigm with parafoveal flanker words,
      observed no such general preview benefit in ERPs, but instead reported N400
      effects triggered by semantically incongruous parafoveal words. To follow up on
      these discrepant findings and to extend them to a nonalphabetic writing system,
      we conducted two ERP experiments with Chinese readers using the RSVP-with
      flankers paradigm and rigorous fixation control via eye tracking. We replicate
      robust parafoveal N400 semantic congruency effects in Chinese participants.
      Additionally, we found that, once a word was directly looked at, words after a
      valid preview elicited a smaller N1 and a weaker N400 than those after an invalid
      preview. Results underline the importance of considering parafoveal vision in ERP
      studies on reading. 

PMID- 26289549
TI  - Postmenopausal hormone therapy and the risk of breast cancer in Norway.
AB  - There is convincing evidence that combined estrogen-progestin therapy (EPT)
      increases the risk of breast cancer. However, the effect of different
      formulations, preparations and routes of administration is largely unknown.
      Estrogen only-therapy (ET) is, in general, not associated or weakly associated
      with breast cancer risk. We investigated the effect of hormone therapy (HT) with
      ET, EPT, and tibolone on risk of invasive breast cancer. Information on HT use
      was obtained from the Norwegian Prescription Database, and breast cancer
      incidence from the Cancer Registry of Norway. Poisson regression was used to
      estimate the incidence rate ratios (RR). We analyzed data from 686,614 Norwegian
      women, aged 45-79 years in January 2004, followed until December 2008, of whom
      178,383 (26%) were prescribed HT. During the average 4.8 years of follow-up,
      7,910 invasive breast cancers were registered. Compared with nonusers, current
      users of estradiol-norethisterone acetate (NETA)(EPT) had a RR of 2.74 (95% CI:
      2.55-2.95). Users of the high dose estradiol-NETA formulation Kliogest((r)) had a
      RR of 3.26 (95% CI: 2.84-3.73), while users of the low dose Activelle((r)) had a
      RR of 2.76 (95% CI: 2.51-3.04). Current users of tibolone had a RR of 1.91 (95%
      CI: 1.61-2.28). Current users of ET with oral or transdermal estradiol had a RR
      of 1.40 (95% CI: 1.16-1.68), and 1.40 (95% CI: 1.00-1.95), respectively. The
      increased incidence rates approximates one extra invasive breast cancer case
      diagnosed for every 259 women using estradiol-NETA for one year, and one extra
      case for every 475 women using tibolone. In conclusion, use of estradiol-NETA and
      tibolone preparations is associated with an increased breast cancer risk. 

PMID- 26289550
TI  - Total chemical synthesis of the site-selective azide-labeled [I66A]HIV-1
      protease.
AB  - The first total chemical synthesis of the site-selective azide-labeled [I66A]HIV
      1 protease is described by native chemical ligation. Chemical synthesis of azide
      labeled proteins would provide useful protein tools for biochemical, biophysical
      or medical studies. 

PMID- 26289551
TI  - MGMT methylation assessment in glioblastoma: MS-MLPA versus human methylation
      450K beadchip array and immunohistochemistry.
AB  - PURPOSE: The MGMT gene encodes a DNA repair enzyme that counteracts with
      chemotherapy efficiency, specifically with alkylating agents such as temozolomide
      (TMZ). It is well established that MGMT methylation should be screened as a
      predictive marker for TMZ in glioblastoma, and we thus aimed to determine a
      reliable and practical diagnostic method of MGMT methylation detection. PATIENTS
      AND METHODS: 55 glioblastomas were investigated for MGMT methylation status using
      methylation-specific multiplexed ligation probe amplification (MS-MLPA), illumina
      human methylation 450K BeadChip array (HM450 K) analysis, and compared to MGMT
      protein expression by immunohistochemistry (IHC) staining. The methylation status
      of promoter, intron and all MGMT CpG targeted sites were separately correlated to
      patient's survival. RESULTS: In addition to MS-MLPA and 450 K concordance, our
      results showed significantly higher overall survival (OS) of patients receiving
      TMZ and presenting MGMT methylated promoter (mean OS = 21.5 months, p = 0.046).
      Including all glioblastoma cases and regardless of chemotherapy, MS-MLPA showed
      significant survival difference between MGMT methylated and unmethylated cases
      (mean OS = 13, p = 0.021). CONCLUSION: We concluded that in glioblastoma, MGMT
      promoter methylation predicts TMZ sensitivity. This current comparative analysis
      leads to consider that MS-MLPA is a valuable as HM450 K array for MGMT
      methylation status screening.

PMID- 26289552
TI  - Neutrophil to lymphocyte and platelet to lymphocyte ratios increase in ovarian
      tumors in the presence of frank stromal invasion.
AB  - OBJECTIVE: The aim of this study was to assess the predictive value of
      neutrophil/lymphocyte and platelet/lymphocyte ratios for borderline, malignant
      ovarian tumors, and borderline cases with microinvasion. METHODS: Totally 275
      women with sonographically detected ovarian tumor were enrolled for this study.
      All subjects underwent gynecological surgery via endoscopic or conventional
      approach and ovarian masses were all evaluated histopathologically by the same
      pathologist. All study population was divided into three groups as group with
      borderline tumors, benign tumors, or malignant tumors according to the
      histopathological diagnosis. Just before surgical intervention, a blood sample
      was obtained from each participant to analyze CA125 level, neutrophil, platelet,
      and lymphocyte count. RESULTS: Neutrophil/lymphocyte ratio (AUC = 0.604, P =
      0.02) was a significant predictor for malignant cases. Optimal cutoff value for
      the neutrophil/lymphocyte ratio was found to be 2.47 with 63.4% sensitivity and
      63.5% specificity for malignancy prediction. Odds ratio of high
      neutrophil/lymphocyte ratio for malignancy risk was 2.5 (95% CI 1.3-4.8, P =
      0.004). Platelet/lymphocyte ratio (AUC = 0.621, P = 0.007) was a significant
      predictor for malignant cases. Platelet/lymphocyte ratio (AUC = 0.568, P = 0.05)
      was also predictive for cases without a benign mass. Optimal cutoff value for the
      platelet/lymphocyte ratio was found to be 144.3 with 54% sensitivity and 59%
      specificity for malignancy prediction. Odds ratio of high platelet/lymphocyte
      ratio for malignancy risk was 2.1 (95% CI 1.1-3.8, P = 0.02). CONCLUSION:
      Neutrophil/lymphocyte and platelet/lymphocyte ratios are predictors for malignant
      ovarian tumors but not borderline tumors even in case of microinvasion.

PMID- 26289553
TI  - Phototherapy in transport for neonates with unconjugated hyperbilirubinaemia.
AB  - AIM: In Victoria, neonates with severe unconjugated hyperbilirubinaemia at risk
      of requiring exchange transfusion are retrieved by the Paediatric Infant
      Perinatal Emergency Retrieval Service and transferred to a Neonatal Intensive
      Care Unit where an exchange transfusion can be performed if necessary. Transfer
      may result in prolonged periods without phototherapy in neonates at risk of
      developing bilirubin encephalopathy. We aimed to describe our experience of the
      introduction of phototherapy using a portable phototherapy unit during transport.
      METHODS: Neonates with a primary diagnosis of severe unconjugated
      hyperbilirubinaemia were identified from the Paediatric Infant Perinatal
      Emergency Retrieval clinical database over an 11-year period. Demographic and
      clinical data including gestation, age at transport, serum bilirubin levels pre-
      and post-transport, use of phototherapy during transport (PTDT), likely
      diagnosis, and use of exchange transfusion were included. RESULTS: A total of 147
      neonates were included with 104 neonates receiving PTDT and 43 who did not.
      Neonates who received PTDT were less likely to require exchange transfusion,
      19.2% versus 34.9%, odds ratio 0.44 (95% CI 0.2-0.98), P = 0.05. However, after
      correction for factors appearing to be related to use of exchange transfusion,
      the odds ratio increased to 0.58 (95% CI 0.21-1.63), P = 0.3. There was a greater
      reduction in the pre- to post-transport total serum bilirubin levels (MUmol/L)
      for the group receiving PTDT (mean 46.3, SD 64.6) versus no PTDT (mean 26.1, SD
      62.5), but this did not reach significance, P = 0.08. CONCLUSIONS: Phototherapy
      during neonatal transport is feasible and safe and may result in a decreased
      requirement for subsequent exchange transfusion.

PMID- 26289554
TI  - Characterization of Early Enzymes Involved in TDP-Aminodideoxypentose
      Biosynthesis en Route to Indolocarbazole AT2433.
AB  - The characterization of TDP-alpha-D-glucose dehydrogenase (AtmS8), TDP-alpha-D
      glucuronic acid decarboxylase (AtmS9), and TDP-4-keto-alpha-D-xylose 2,3
      dehydratase (AtmS14), involved in Actinomadura melliaura AT2433
      aminodideoxypentose biosynthesis, is reported. This study provides the first
      biochemical evidence that both deoxypentose and deoxyhexose biosynthetic pathways
      share common strategies for sugar 2,3-dehydration/reduction and implicates the
      sugar nucleotide base specificity of AtmS14 as a potential mechanism for sugar
      nucleotide commitment to secondary metabolism. In addition, a re-evaluation of
      the AtmS9 homologue involved in calicheamicin aminodeoxypentose biosynthesis
      (CalS9) reveals that CalS9 catalyzes UDP-4-keto-alpha-D-xylose as the predominant
      product, rather than UDP-alpha-D-xylose as previously reported. Cumulatively,
      this work provides additional fundamental insights regarding the biosynthesis of
      novel pentoses attached to complex bacterial secondary metabolites.

PMID- 26289555
TI  - Low genetic diversity despite multiple introductions of the invasive plant
      species Impatiens glandulifera in Europe.
AB  - BACKGROUND: Invasive species can be a major threat to native biodiversity and the
      number of invasive plant species is increasing across the globe. Population
      genetic studies of invasive species can provide key insights into their invasion
      history and ensuing evolution, but also for their control. Here we genetically
      characterise populations of Impatiens glandulifera, an invasive plant in Europe
      that can have a major impact on native plant communities. We compared populations
      from the species' native range in Kashmir, India, to those in its invaded range,
      along a latitudinal gradient in Europe. For comparison, the results from 39 other
      studies of genetic diversity in invasive species were collated. RESULTS: Our
      results suggest that I. glandulifera was established in the wild in Europe at
      least twice, from an area outside of our Kashmir study area. Our results further
      revealed that the genetic diversity in invasive populations of I. glandulifera is
      unusually low compared to native populations, in particular when compared to
      other invasive species. Genetic drift rather than mutation seems to have played a
      role in differentiating populations in Europe. We find evidence of limitations to
      local gene flow after introduction to Europe, but somewhat less restrictions in
      the native range. I. glandulifera populations with significant inbreeding were
      only found in the species' native range and invasive species in general showed no
      increase in inbreeding upon leaving their native ranges. In Europe we detect
      cases of migration between distantly located populations. Human activities
      therefore seem to, at least partially, have facilitated not only introductions,
      but also further spread of I. glandulifera across Europe. CONCLUSIONS: Although
      multiple introductions will facilitate the retention of genetic diversity in
      invasive ranges, widespread invasive species can remain genetically relatively
      invariant also after multiple introductions. Phenotypic plasticity may therefore
      be an important component of the successful spread of Impatiens glandulifera
      across Europe.

PMID- 26289556
TI  - Genomic Profiling Reveals Unique Molecular Alterations in Hepatoblastomas and
      Adjacent Hepatocellular Carcinomas in B6C3F1 Mice.
AB  - The cell of origin of hepatoblastoma (HB) in humans and mice is unknown; it is
      hypothesized to be a transformed hepatocyte, oval cell, or hepatic progenitor
      cell. In mice, current dogma is that HBs arise from preexisting hepatocellular
      neoplasms as a result of further neoplastic transformation. However, there is
      little evidence supporting this direct relationship. To better understand the
      relationship between hepatocellular carcinoma (HCC) and HB and determine
      molecular similarities between mouse and human HB, global gene expression
      analysis and targeted mutation analysis were performed using HB, HCC, and
      adjacent liver from the same animals in a recent National Toxicology Program
      bioassay. There were significant differences in Hras and Ctnnb1 mutation spectra,
      and by microarray, HBs showed dysregulation of embryonic development, stem cell
      pluripotency, and genomic imprinting compared to HCC. Meta-analysis showed
      similarities between HB, early mouse embryonic liver, and hepatocyte-derived
      stem/progenitor cells compared to HCC. Our data show that there are striking
      differences between HB and HCC and suggest that HB is a significantly different
      entity that may arise from a hepatic precursor cell. Furthermore, mouse HB is
      similar to the human disease at the pathway level and therefore is likely a
      relevant model for evaluating human cancer hazard. 

PMID- 26289557
TI  - Levosimendan Improves Clinical Outcomes of Refractory Heart Failure in Elderly
      Chinese Patients.
AB  - BACKGROUND: Levosimendan has been extensively used to treat heart failure (HF)
      for nearly 10 years, but data on levosimendan used in elderly patients with
      refractory HF remains limited. This study aimed to investigate the effects of
      levosimendan on elderly patients with intractable HF. MATERIAL AND METHODS: A
      total of 268 patients with HF (over 70 years, New York Heart Association [NYHA]
      classification III-IV, LVEF <=40%, plasma NT-proBNP >=1000 pg/mL) received
      conventional anti-HF therapies for 2 weeks. Such therapies include the limiting
      of salt intake, increasing myocardial contractility (without levosimendan),
      inducing urine, antagonizing aldosterone, antagonizing myocardial remodeling,
      and, if necessary, using antibiotics. Our study included 42 patients without
      symptoms whose improvement was re-evaluated and presented in NYHA class III-IV,
      LVEF <=40%, plasma NT-proBNP >=1000.0 pg/mL, and serum creatinine <110.0 umol/L.
      These patients were divided into an experimental groups (n=21, treated with
      levosimendan) and a control group (n=21, continuously given regular treatment as
      before). After 1 week, 42 patients were assessed for changes in NYHA
      classification, LVEF, and NT-proBNP. RESULTS: No severe complications related to
      levosimendan were noted. Compared with the control group, NYHA classification (I
      II: 1 versus 21, III-IV: 20 versus 0, P<0.05) and LVEF (30.62+/-6.19% versus
      45.83+/-5.06%, P<0.05) were increased, and plasma NT-proBNP was reduced (458.35+/
      193.16 pg/mL versus 2921.52+/-1395.97 pg/mL, P<0.05) in the experimental group.
      CONCLUSIONS: Our study showed levosimendan significantly and safely improved
      clinical outcomes of refractory heart failure in elderly patients.

PMID- 26289558
TI  - Impact of migration origin on individual protection strategies against sexual
      transmission of HIV in Paris metropolitan area, SIRS cohort study, France.
AB  - BACKGROUND: The impact of migration and country or region of origin on sexual
      behaviours and prevention of the sexual transmission of HIV has been scarcely
      studied in France. The objective of this study was to evaluate if and how
      individual attitudes of prevention towards HIV infection are different according
      to country or region of origins in Paris area, France. METHODS: 3006 individuals
      were interviewed in the Paris metropolitan area in 2010. Outcome variables were
      (i) the intention of the individual to protect oneself against HIV, and (ii) the
      adoption of a condom-based approach for protection against HIV. To explore
      factors associated with these outcomes, we constructed multivariate logistic
      regression models, first taking into account only demographic variables 
      including country of origin-, then successively adding socioeconomic variables
      and variables related to sexual behaviour and HIV perception and prevention
      behaviour. RESULTS: French and foreign people who have origins in Sub-Saharan
      Africa declared more intentions to protect themselves than French people with
      French parents (in foreign men, aOR = 3.43 [1.66-7.13]; in foreign women, aOR =
      2.94 [1.65-5.23]), but did not declare more recourse to a condom-based approach
      for protection against HIV (in foreign men, aOR = 1.38 [0.38-4.93]; in foreign
      women, aOR = 0.93 [0.40-2.18]). Conversely, foreign women and French women from
      foreign origin, especially from Maghreb (Northern Africa), reported less
      intention of protection than French women with French parents. CONCLUSIONS: These
      results underline the importance of taking culture and origins of target
      populations into consideration when designing information, education and
      communication about HIV and sexually transmitted diseases. These results also
      draw attention to fractions of the general population that could escape from
      prevention messages.

PMID- 26289559
TI  - Systematic review of clinical practice guidelines recommendations about primary
      cardiovascular disease prevention for older adults.
AB  - BACKGROUND: Clinical care for older adults is complex and represents a growing
      problem. They are a diverse patient group with varying needs, frequent presence
      of multiple comorbidities, and are more susceptible to treatment harms. Thus
      Clinical Practice Guidelines (CPGs) need to carefully consider older adults in
      order to guide clinicians. We reviewed CPG recommendations for primary
      cardiovascular disease (CVD) prevention and examined the extent to which CPGs
      address issues important for older people identified in the literature. METHODS:
      We searched: 1) two systematic reviews on CPGs for CVD prevention and 2) the
      National CPG Clearinghouse, G-I-N International CPG Library and Trip databases
      for CPGs for CVD prevention, hypertension and cholesterol. We conducted our
      search between April and December 2013. We excluded CPGs for diabetes, chronic
      kidney disease, HIV, lifestyle, general screening/prevention, and pregnant or
      pediatric populations. Three authors independently screened citations for
      inclusion and extracted data. The primary outcomes were presence and extent of
      recommendations for older people including discussion of: (1) available evidence,
      (2) barriers to implementation of the CPG, and (3) tailoring management for this
      group. RESULTS: We found 47 eligible CPGs. There was no mention of older people
      in 4 (9 %) of the CPGs. Benefits were discussed more frequently than harms.
      Twenty-three CPGs (49 %) discussed evidence about potential benefits and 18 (38
      %) discussed potential harms of CVD prevention in older people. Most CPGs
      addressed one or more barriers to implementation, often as a short statement.
      Although 27 CPGs (58 %) mentioned tailoring management to the older patient
      context (e.g. comorbidities), concrete guidance was rare. CONCLUSION: Although
      most CVD prevention CPGs mention the older population to some extent, the
      information provided is vague and very limited. Older adults represent a growing
      proportion of the population. Guideline developers must ensure they consider
      older patients' needs and provide appropriate advice to clinicians in order to
      support high quality care for this group. CPGs should at a minimum address the
      available evidence about CVD prevention for older people, and acknowledge the
      importance of patient involvement.

PMID- 26289561
TI  - First identification of Flatbush diabetes in patients of Indian origin.

PMID- 26289560
TI  - Core Outcomes in Ventilation Trials (COVenT): protocol for a core outcome set
      using a Delphi survey with a nested randomised trial and observational cohort
      study.
AB  - BACKGROUND: Among clinical trials of interventions that aim to modify time spent
      on mechanical ventilation for critically ill patients there is considerable
      inconsistency in chosen outcomes and how they are measured. The Core Outcomes in
      Ventilation Trials (COVenT) study aims to develop a set of core outcomes for use
      in future ventilation trials in mechanically ventilated adults and children.
      METHODS/DESIGN: We will use a mixed methods approach that incorporates a
      randomised trial nested within a Delphi study and a consensus meeting.
      Additionally, we will conduct an observational cohort study to evaluate uptake of
      the core outcome set in published studies at 5 and 10 years following core
      outcome set publication. The three-round online Delphi study will use a list of
      outcomes that have been reported previously in a review of ventilation trials.
      The Delphi panel will include a range of stakeholder groups including patient
      support groups. The panel will be randomised to one of three feedback methods to
      assess the impact of the feedback mechanism on subsequent ranking of outcomes. A
      final consensus meeting will be held with stakeholder representatives to review
      outcomes. DISCUSSION: The COVenT study aims to develop a core outcome set for
      ventilation trials in critical care, explore the best Delphi feedback mechanism
      for achieving consensus and determine if participation increases use of the core
      outcome set in the long term.

PMID- 26289562
TI  - Improvement of Topical Palmitoylethanolamide Anti-Inflammatory Activity by
      Pegylated Prodrugs.
AB  - A small library of polyethylene glycol esters of palmitoylethanolamide (PEA) was
      synthesized with the aim of improving the pharmacokinetic profile of the parent
      drug after topical administration. Synthesized prodrugs were studied for their
      skin accumulation, pharmacological activities, in vitro chemical stability, and
      in silico enzymatic hydrolysis. Prodrugs proved to be able to delay and prolong
      the pharmacological activity of PEA by modification of its skin accumulation
      profile. Pharmacokinetic improvements were particularly evident when specific
      structural requirements, such as flexibility and reduced molecular weight, were
      respected. Some of the synthesized prodrugs prolonged the pharmacological effects
      5 days following topical administration, while a formulation composed by PEA and
      two pegylated prodrugs showed both rapid onset and long-lasting activity,
      suggesting the potential use of polyethylene glycol prodrugs of PEA as a suitable
      candidate for the treatment of skin inflammatory diseases. 

PMID- 26289564
TI  - Brief, Rapid Response, Parenting Interventions Within Primary Care Settings.
AB  - Opportunities created by the Patient Protection and Affordable Care Act along
      with the increased prevalence of pediatric behavioral and mental health concerns
      provide new challenges for pediatric health care providers. To address these
      matters, providers need to change the manner by which they provide health care to
      families. A novel approach is providing brief, rapid response, evidence-based
      parenting interventions within the pediatric primary care setting. Family-focused
      parenting programs support the American Academy of Pediatrics recommendations of
      improving mental health via supports in pediatric primary care to maximize the
      social and psychological well-being of families. A considerable body of research
      indicates that parenting interventions reduce the severity and frequency of
      disruptive behavior disorders in children and provide support to parent by
      bolstering parental resilience and improving overall family functioning.
      Providing these services within the pediatric primary care setting addresses the
      need for fully integrated health services that are family-centered and easily
      accessible.

PMID- 26289565
TI  - All oxide semiconductor-based bidirectional vertical p-n-p selectors for 3D
      stackable crossbar-array electronics.
AB  - Three-dimensional (3D) stackable memory devices including nano-scaled crossbar
      array are central for the realization of high-density non-volatile memory
      electronics. However, an essential sneak path issue affecting device performance
      in crossbar array remains a bottleneck and a grand challenge. Therefore, a
      suitable bidirectional selector as a two-way switch is required to facilitate a
      major breakthrough in the 3D crossbar array memory devices. Here, we show the
      excellent selectivity of all oxide p-/n-type semiconductor-based p-n-p open-based
      bipolar junction transistors as selectors in crossbar memory array. We report
      that bidirectional nonlinear characteristics of oxide p-n-p junctions can be
      highly enhanced by manipulating p-/n-type oxide semiconductor characteristics. We
      also propose an associated Zener tunneling mechanism that explains the unique
      features of our p-n-p selector. Our experimental findings are further extended to
      confirm the profound functionality of oxide p-n-p selectors integrated with
      several bipolar resistive switching memory elements working as storage nodes. 

PMID- 26289563
TI  - Methods to Improve the Selection and Tailoring of Implementation Strategies.
AB  - Implementing behavioral health interventions is a complicated process. It has
      been suggested that implementation strategies should be selected and tailored to
      address the contextual needs of a given change effort; however, there is limited
      guidance as to how to do this. This article proposes four methods (concept
      mapping, group model building, conjoint analysis, and intervention mapping) that
      could be used to match implementation strategies to identified barriers and
      facilitators for a particular evidence-based practice or process change being
      implemented in a given setting. Each method is reviewed, examples of their use
      are provided, and their strengths and weaknesses are discussed. The discussion
      includes suggestions for future research pertaining to implementation strategies
      and highlights these methods' relevance to behavioral health services and
      research.

PMID- 26289566
TI  - Discerning the differential molecular pathology of proliferative middle ear
      lesions using Raman spectroscopy.
AB  - Despite its widespread prevalence, middle ear pathology, especially the
      development of proliferative lesions, remains largely unexplored and poorly
      understood. Diagnostic evaluation is still predicated upon a high index of
      clinical suspicion on otoscopic examination of gross morphologic features. We
      report the first technique that has the potential to non-invasively identify two
      key lesions, namely cholesteatoma and myringosclerosis, by providing real-time
      information of differentially expressed molecules. In addition to revealing
      signatures consistent with the known pathobiology of these lesions, our
      observations provide the first evidence of the presence of carbonate- and
      silicate-substitutions in the calcium phosphate plaques found in
      myringosclerosis. Collectively, these results demonstrate the potential of Raman
      spectroscopy to not only provide new understanding of the etiology of these
      conditions by defining objective molecular markers but also aid in margin
      assessment to improve surgical outcome. 

PMID- 26289569
TI  - Neurodegenerative disease: A neutrophil invasion.

PMID- 26289572
TI  - Finding the engram.
AB  - Many attempts have been made to localize the physical trace of a memory, or
      engram, in the brain. However, until recently, engrams have remained largely
      elusive. In this Review, we develop four defining criteria that enable us to
      critically assess the recent progress that has been made towards finding the
      engram. Recent 'capture' studies use novel approaches to tag populations of
      neurons that are active during memory encoding, thereby allowing these engram
      associated neurons to be manipulated at later times. We propose that findings
      from these capture studies represent considerable progress in allowing us to
      observe, erase and express the engram. 

PMID- 26289573
TI  - Auditory dysfunction in schizophrenia: integrating clinical and basic features.
AB  - Schizophrenia is a complex neuropsychiatric disorder that is associated with
      persistent psychosocial disability in affected individuals. Although studies of
      schizophrenia have traditionally focused on deficits in higher-order processes
      such as working memory and executive function, there is an increasing realization
      that, in this disorder, deficits can be found throughout the cortex and are
      manifest even at the level of early sensory processing. These deficits are highly
      amenable to translational investigation and represent potential novel targets for
      clinical intervention. Deficits, moreover, have been linked to specific
      structural abnormalities in post-mortem auditory cortex tissue from individuals
      with schizophrenia, providing unique insights into underlying pathophysiological
      mechanisms. 

PMID- 26289576
TI  - Activity landscape of DNA methyltransferase inhibitors bridges chemoinformatics
      with epigenetic drug discovery.
AB  - INTRODUCTION: Activity landscapes are valuable tools for exploring systematically
      the structure-activity relationships (SAR) of chemical databases. Their
      application to analyze the SAR of DNA methyltransferase (DNMT) inhibitors, which
      are attractive compounds as potential epi-drugs or epi-probes, provides useful
      information to identify pharmacophoric regions and plan the development of
      predictive models and virtual screening. AREAS COVERED: This paper highlights
      different approaches for conducting SAR analysis of datasets with a particular
      focus on the activity landscape methodology. SAR information of DNMT inhibitors
      (DNMTi), stored in a public database, is surveyed to further illustrate concepts
      and generalities of activity landscape modeling with a special emphasis on
      structure-activity similarity (SAS) maps. EXPERT OPINION: The increasing SAR
      information reported for DNMTi opens up avenues to implement activity landscape
      methods. Despite several activity landscape methods, such as SAS maps, being well
      established, these need further refinement. For instance, novel combinations of
      multiple representations, such as the addition of Z-values of similarity (fusion
      Z), lead to more robust representations of consensus SAS maps. Density SAS maps
      improve the visualization of the SAR. A survey of activity cliffs (i.e., pairs of
      compounds with high structural similarity but high differences in potency) of
      DNMTi available in a public database suggest that it is feasible to develop
      predictive models for non-nucleoside DNMTi using approaches such as quantitative
      structure-activity relationships and that non-nucleoside DNMTi in ChEMBL can be
      used as query molecules in similarity-based virtual screening.

PMID- 26289577
TI  - Simulation with quantum mechanics/molecular mechanics for drug discovery.
AB  - INTRODUCTION: Biological macromolecules, such as proteins or nucleic acids, are
      (still) molecules and thus they follow the same chemical rules that any simple
      molecule follows, even if their size generally renders accurate studies
      unhelpful. However, in the context of drug discovery, a detailed analysis of
      ligand association is required for understanding or predicting their interactions
      and hybrid quantum mechanics/molecular mechanics (QM/MM) computations are
      relevant tools to help elucidate this process. AREAS COVERED: In this review, the
      authors explore the use of QM/MM for drug discovery. After a brief description of
      the molecular mechanics (MM) technique, the authors describe the subtractive and
      additive techniques for QM/MM computations. The authors then present several
      application cases in topics involved in drug discovery. EXPERT OPINION: QM/MM
      have been widely employed during the last decades to study chemical processes
      such as enzyme-inhibitor interactions. However, despite the enthusiasm around
      this area, plain MM simulations may be more meaningful than QM/MM. To obtain
      reliable results, the authors suggest fixing several keystone parameters
      according to the underlying chemistry of each studied system.

PMID- 26289574
TI  - From the genetic architecture to synaptic plasticity in autism spectrum disorder.
AB  - Genetics studies of autism spectrum disorder (ASD) have identified several risk
      genes that are key regulators of synaptic plasticity. Indeed, many of the risk
      genes that have been linked to these disorders encode synaptic scaffolding
      proteins, receptors, cell adhesion molecules or proteins that are involved in
      chromatin remodelling, transcription, protein synthesis or degradation, or actin
      cytoskeleton dynamics. Changes in any of these proteins can increase or decrease
      synaptic strength or number and, ultimately, neuronal connectivity in the brain.
      In addition, when deleterious mutations occur, inefficient genetic buffering and
      impaired synaptic homeostasis may increase an individual's risk for ASD. 

PMID- 26289575
TI  - Fluorescence anisotropy (polarization): from drug screening to precision
      medicine.
AB  - INTRODUCTION: Fluorescence anisotropy (FA) is one of the major established
      methods accepted by industry and regulatory agencies for understanding the
      mechanisms of drug action and selecting drug candidates utilizing a high
      throughput format. AREAS COVERED: This review covers the basics of FA and
      complementary methods, such as fluorescence lifetime anisotropy and their roles
      in the drug discovery process. The authors highlight the factors affecting FA
      readouts, fluorophore selection and instrumentation. Furthermore, the authors
      describe the recent development of a successful, commercially valuable FA assay
      for long QT syndrome drug toxicity to illustrate the role that FA can play in the
      early stages of drug discovery. EXPERT OPINION: Despite the success in drug
      discovery, the FA-based technique experiences competitive pressure from other
      homogeneous assays. That being said, FA is an established yet rapidly developing
      technique, recognized by academic institutions, the pharmaceutical industry and
      regulatory agencies across the globe. The technical problems encountered in
      working with small molecules in homogeneous assays are largely solved, and new
      challenges come from more complex biological molecules and nanoparticles. With
      that, FA will remain one of the major work-horse techniques leading to precision
      (personalized) medicine.

PMID- 26289578
TI  - An overview of peptide and peptoid foldamers in medicinal chemistry.
AB  - INTRODUCTION: Foldamers are artificial self-organizing systems with various
      critical properties: i) a stable and designable secondary structure; ii) a larger
      molecular surface as compared with ordinary organic drug molecules; iii)
      appropriate control of the orientation of the side-chain functional groups; iv)
      resistance against proteolytic degradation, which leads to potentially increased
      oral bioavailability and a longer serum half-life relative to ordinary alpha
      peptides; and v) the lower conformational freedom may result in increased
      receptor binding in comparison with the natural analogs. AREAS COVERED: This
      article covers the general properties and types of foldamers. This includes
      highlighted examples of medicinal chemical applications, including antibacterial
      and cargo molecules, anti-Alzheimer compounds and protein-protein interaction
      modifiers. EXPERT OPINION: Various new foldamers have been created with a range
      of structures and biological applications. Membrane-acting antibacterial
      foldamers have been introduced. A general property of these structures is their
      amphiphilic nature. The amphiphilicity can be stationary or induced by the
      membrane binding. Cell-penetrating foldamers have been described which serve as
      cargo molecules, and foldamers have been used as autophagy inducers. Anti
      Alzheimer compounds too have been created and the greatest breakthrough was
      attained via the modification of protein-protein interactions. This can serve as
      the chemical and pharmaceutical basis for the relevance of foldamers in the
      future.

PMID- 26289580
TI  - Sleep stage classification with ECG and respiratory effort.
AB  - Automatic sleep stage classification with cardiorespiratory signals has attracted
      increasing attention. In contrast to the traditional manual scoring based on
      polysomnography, these signals can be measured using advanced unobtrusive
      techniques that are currently available, promising the application for personal
      and continuous home sleep monitoring. This paper describes a methodology for
      classifying wake, rapid-eye-movement (REM) sleep, and non-REM (NREM) light and
      deep sleep on a 30 s epoch basis. A total of 142 features were extracted from
      electrocardiogram and thoracic respiratory effort measured with respiratory
      inductance plethysmography. To improve the quality of these features, subject
      specific Z-score normalization and spline smoothing were used to reduce between
      subject and within-subject variability. A modified sequential forward selection
      feature selector procedure was applied, yielding 80 features while preventing the
      introduction of bias in the estimation of cross-validation performance. PSG data
      from 48 healthy adults were used to validate our methods. Using a linear
      discriminant classifier and a ten-fold cross-validation, we achieved a Cohen's
      kappa coefficient of 0.49 and an accuracy of 69% in the classification of wake,
      REM, light, and deep sleep. These values increased to kappa = 0.56 and accuracy =
      80% when the classification problem was reduced to three classes, wake, REM
      sleep, and NREM sleep. 

PMID- 26289579
TI  - Gastroprotective effect of carob (Ceratonia siliqua L.) against ethanol-induced
      oxidative stress in rat.
AB  - BACKGROUND: We aimed in the present study, at investigating the gastroprotective
      effect of carob pods aqueous extract (CPAE) against ethanol-induced oxidative
      stress in rats as well as the mechanism implicated. METHODS: Adult male wistar
      rats were used and divided into six groups of ten each: control, EtOH (80% v/v, 4
      g/kg b.w.), EtOH 80% + various doses of CPAE (500, 1000 and 2000 mg/kg, b.w.) and
      EtOH + Famotidine (10 mg/kg, p.o.) Animals were perorally (p.o.) pre-treated with
      CPAE during 15 days and intoxicated with a single oral administration of EtOH (4
      g/kg b.w.) for two hours. RESULTS: The colorimetric analysis demonstrated that
      the CPAE exhibited an importance in vitro antioxidant activity against ABTS and
      DPPH radicals. We found that CPAE pretreatment in vivo, protected against EtOH
      induced macroscopic and histological changes induced in stomach mucosa. Carob
      extract administration also protected against alcohol-induced volume gastric
      juice decrease. More importantly, We showed that CPAE counteracted EtOH-induced
      gastric lipoperoxidation, reversed the decrease of sulfhydryl groups (-SH) an
      hydrogen peroxide (H2O2) levels, and prevented the depletion of antioxidant
      enzyme activity of superoxide dismutase (SOD), catalase (CAT) and glutathione
      peroxidase (GPx). CONCLUSIONS: These findings suggest that CPAE exerted a
      potential gastro-protective effect against EtOH-induced oxidative stress in rats,
      due in part, to its antioxidants properties.

PMID- 26289582
TI  - The Exploration of Health-Related Quality of Life.
AB  - The purpose of this study was to explore quality of life (QoL) and the factors
      influencing QoL in gynecological cancer patients. One hundred sixty-seven
      patients with gynecologic cancers were recruited from a district hospital in
      Southern Taiwan. The instruments used included the European Organization for
      Research and Treatment of Cancer Quality of Life Questionnaire Core-30 Version
      3.0 in Chinese (EORTC QLQ-C30), the Symptom Distress Scale, and demographic
      characteristics and disease-related variables. The results showed that the mean
      score for the QLQ-C30 was 61.13 ( SD = 22.71). In the stepwise regression model,
      two factors predicted overall global QoL: symptom distress (33.8%) and current
      occupation (2.2%). These predictors accounted for 36.0% of the total variance.
      These results showed that symptom distress was a predictor of QoL. This study
      provides a reference for use when designing improved educational care programs
      that reduce patient symptom distress and enhance gynecologic cancer patients'
      QoL.

PMID- 26289581
TI  - Association between blood glucose variability and coronary plaque instability in
      patients with acute coronary syndromes.
AB  - BACKGROUND: Blood glucose variability is receiving considerable attention as a
      new risk factor for coronary artery disease. This study aimed to investigate the
      association between blood glucose variability and coronary plaque tissue
      characteristics. METHODS: In 57 patients with acute coronary syndrome, integrated
      backscatter intravascular ultrasound (IB-IVUS) and gray-scale IVUS were performed
      before balloon dilatation or stent implantation in the culprit vessels. Standard
      IVUS indices were evaluated for volume index (volume/length), and plaque
      components were measured by IB-IVUS for percent tissue volume. In addition to
      conventional glucose indicators, blood glucose variability in a stable state was
      determined by calculating the mean amplitude of glycemic excursions (MAGE) using
      a continuous glucose monitoring system. RESULTS: Higher MAGE values were
      significantly correlated with larger percent plaque volumes (r = 0.32, p =
      0.015), and increased lipid (r = 0.44, p = 0.0006) and decreased fibrous (r = 
      0.45, p = 0.0005) plaque components. In contrast, HbA1c or fasting plasma glucose
      values were not significantly correlated with plaque volumes and percent plaque
      components. Homeostasis model assessment of insulin resistance values were
      positively correlated with vessel (r = 0.35, p = 0.007) and plaque (r = 0.27, p =
      0.046) volumes, but not with percent plaque components. In multiple regression
      analysis, higher MAGE values were independently associated with increased lipid
      (beta = 0.80, p = 0.0035) and decreased fibrous (beta = -0.79, p = 0.0034)
      contents in coronary plaques. CONCLUSIONS: Among all glucose indicators studied,
      only higher blood glucose variability was an independent determinant of increased
      lipid and decreased fibrous contents with larger plaque burden, suggesting blood
      glucose variability as one of the important factors related to coronary plaque
      vulnerability.

PMID- 26289583
TI  - Impact of Antihypertensive Agents on Central Systolic Blood Pressure and
      Augmentation Index: A Meta-Analysis.
AB  - BACKGROUND: New evidence suggests that central systolic blood pressure (cSBP) and
      augmentation index (AI) are superior predictors of adverse cardiovascular
      outcomes compared to peripheral systolic BP (pSBP). We performed a meta-analysis
      assessing the impact of antihypertensives on cSBP and AI. METHODS: PubMed,
      Cochrane Library, and CINAHL were searched until September 2014 to identify
      eligible articles. A DerSimonian and Laird random-effects model was used to
      calculate the weighted mean difference (WMD) and its 95% confidence interval
      (CI). Fifty-two and 58 studies incorporating 4,381 and 3,716 unique subjects were
      included for cSBP and AI analysis, respectively. RESULTS: Overall,
      antihypertensives reduced pSBP more than cSBP (WMD 2.52 mm Hg, 95% CI 1.35 to
      3.69; I (2) = 21.9%). beta-Blockers (BBs) posed a significantly greater reduction
      in pSBP as compared to cSBP (WMD 5.19 mm Hg, 95% CI 3.21 to 7.18). alpha
      Blockers, angiotensin converting enzyme inhibitors, angiotensin II receptor
      blockers, calcium channel blockers, diuretics, renin-angiotensin aldosterone
      system inhibitors and nicorandil reduced cSBP and pSBP in a similar manner. The
      overall reduction in AI from baseline was 3.09% (95% CI 2.28 to 3.90; I (2) =
      84.5%). A significant reduction in AI was seen with angiotensin converting enzyme
      inhibitors, angiotensin II receptor blockers, calcium channel blockers,
      diuretics, renin-angiotensin aldosterone system inhibitors, BBs, alpha-blockers
      (ABs), nicorandil, and moxonidine reduced AI nonsignificantly. CONCLUSIONS: BBs
      are not as beneficial as the other antihypertensives in reducing cSBP and AI.

PMID- 26289585
TI  - Croceifilum oryzae gen. nov., sp. nov., isolated from rice paddy soil.
AB  - A mesophilic, aerobic, Gram-stain-positive, filamentous bacterial strain,
      designated ZYf1a3T, was isolated from rice paddy soil in Japan. This strain grew
      on a solid medium with formation of substrate mycelium; endospores were produced
      singly along the mycelium. Formation of aerial mycelium was not observed on any
      of the media tested. This strain produced a characteristic saffron yellow soluble
      pigment. Cloned 16S rRNA gene sequences of strain ZYf1a3T yielded three different
      copies (similarity between the three sequences: 99.8-99.9 %). One of these
      sequences had one base deletion. Phylogenetic analysis based on 16S rRNA gene
      sequences indicated that strain ZYf1a3T belongs to an independent phylogenetic
      lineage of the family Thermoactinomycetaceae. The cell wall of strain ZYf1a3T
      contained meso-diaminopimelic acid, alanine and glutamic acid, but no
      characteristic sugars. It contained menaquinone 7 as the sole menaquinone. The
      major cellular fatty acids were iso-C15 : 0 and anteiso-C15 : 0.The major polar
      lipids were phosphatidylethanolamine, diphosphatidylglycerol,
      phosphatidylglycerol, phosphatidyl-N-methylethanolamine and unidentified
      aminophospholipids. The DNA G+C content was 42.5 mol%. From phylogenetic analysis
      based on 16S rRNA gene sequences and phenotypic characteristics, this strain is
      considered to represent a novel species in a new genus, for which the name
      Croceifilum oryzae gen. nov., sp. nov. is proposed. The type strain of
      Croceifilum oryzae is ZYf1a3T ( = JCM 30426T = CCUG 66446T = DSM 46876T).

PMID- 26289584
TI  - Paramagnetic Ligand Tagging To Identify Protein Binding Sites.
AB  - Transient biomolecular interactions are the cornerstones of the cellular
      machinery. The identification of the binding sites for low affinity molecular
      encounters is essential for the development of high affinity pharmaceuticals from
      weakly binding leads but is hindered by the lack of robust methodologies for
      characterization of weakly binding complexes. We introduce a paramagnetic ligand
      tagging approach that enables localization of low affinity protein-ligand binding
      clefts by detection and analysis of intermolecular protein NMR pseudocontact
      shifts, which are invoked by the covalent attachment of a paramagnetic lanthanoid
      chelating tag to the ligand of interest. The methodology is corroborated by
      identification of the low millimolar volatile anesthetic interaction site of the
      calcium sensor protein calmodulin. It presents an efficient route to binding site
      localization for low affinity complexes and is applicable to rapid screening of
      protein-ligand systems with varying binding affinity. 

PMID- 26289586
TI  - Transcranial magnetic stimulation (TMS) for schizophrenia.
AB  - BACKGROUND: People with schizophrenia often experience symptoms which fail to
      fully respond to antipsychotic medication. Transcranial magnetic stimulation
      (TMS) has been proposed as a new treatment for people with schizophrenia,
      especially those who experience persistent auditory hallucinations. OBJECTIVES:
      To estimate the effects of TMS alone, compared with sham TMS or with 'standard
      management' and any other comparison interventions in reducing psychotic symptoms
      associated with schizophrenia. SEARCH METHODS: We searched the Cochrane
      Schizophrenia Group Trials Register (June 2006, June 2008, April 2013). This
      register is compiled by methodical searches of MEDLINE, EMBASE, BIOSIS, CINAHL,
      Dissertation abstracts, LILACS, PSYNDEX, PsycINFO, RUSSMED, and Sociofile, and is
      supplemented with handsearching of relevant journals and numerous conference
      proceedings. SELECTION CRITERIA: We included all randomised controlled trials
      recruiting at least five participants and comparing TMS with sham TMS or any
      other treatment for people with schizophrenia. DATA COLLECTION AND ANALYSIS: We
      extracted data independently. For dichotomous data we calculated relative risks
      (RRs) and their 95% confidence intervals (CIs). For continuous data, we
      calculated mean differences (MD) and 95% CI. We used a fixed-effect model. We
      assessed overall quality of the evidence using the GRADE approach. MAIN RESULTS:
      We included 41 studies with 1473 participants in the review. We found significant
      differences in favour of temporoparietal TMS compared to sham TMS for global
      state measured on the CGI scale (7 RCTs, n = 224, MD -0.5, 95% CI -0.76 to -0.23,
      very low-quality evidence) and positive symptoms measured on the PANSS scale (5
      RCTs, n = 127, MD -6.09, 95% CI -10.95 to -1.22, very low-quality evidence).
      Participants experienced significantly more headaches in the temporoparietal TMS
      group (10 RCTs, n = 392, RR 2.65, 95% CI 1.56 to 4.50, very low-quality
      evidence). However, no more participants left the study early from the TMS group
      than from the sham group (very low-quality evidence). Cognitive state was
      assessed using 39 different measures, and all were equivocal (very low-quality
      evidence).We included only two trials which compared temporoparietal TMS with
      standard treatment. In both trials the participants received first- and second
      generation antipsychotic medication in both treatment groups, therefore TMS was
      used an adjunctive therapy to medication. We found no significant differences in
      the number of participants that showed clinical improvement in global state (1
      RCT, n = 100, RR 1.19, 95% CI 0.91 to 1.57) or left the study early (2 RCTs, n =
      140, RR 0.33, 95% CI 0.08 to 1.46) (both very low-quality evidence). No studies
      reported on global state score, mental state, cognitive state and adverse
      effects.For prefrontal TMS compared to sham TMS, global state was measured on
      three different scales, all of which presented equivocal results (very low
      quality evidence). We could not pool data for mental state on the PANSS scale due
      to high heterogeneity. Cognitive state was assessed using 19 different measures,
      with 15/19 being equivocal (very low-quality evidence). Prefrontal TMS caused
      more headaches (6 RCTs, n = 164, RR 2.77, 95% CI 1.22 to 6.26, very low-quality
      evidence) but there was no difference in the number of participants leaving the
      study early (very low-quality evidence). No studies reported data for clinical
      improvement.We found a significant difference in favour of prefrontal theta burst
      stimulation TMS compared to sham TMS for mental state on the PANNS scale (3 RCTs,
      n = 108, MD -5.71, 95% CI -9.32 to -2.10, very low evidence). We found no
      difference for clinical improvement, cognitive state, number of headaches, and
      leaving the study early (very low-quality evidence).None of the included studies
      reported satisfaction with care. AUTHORS' CONCLUSIONS: Based on this review,
      there is insufficient evidence to support or refute the use of TMS to treat
      symptoms of schizophrenia. Although some evidence suggests that TMS, and in
      particular temporoparietal TMS, may improve certain symptoms (such as auditory
      hallucinations and positive symptoms of schizophrenia) compared to sham TMS, the
      results were not robust enough to be unequivocal across the assessment measures
      used. There was insufficient evidence to suggest any added benefit with TMS used
      as an adjunctive therapy to antipsychotic medication.The overall quality of
      evidence was graded as very low due to risk of bias, and this was accompanied by
      an imprecision in estimates due to the relatively small number of participants in
      the studies. Thus, consideration is required in improving the quality of trial
      processes, as well as the quality of reporting of ongoing and future TMS trials,
      so as to facilitate accurate future judgements in assessing risk of bias.
      Differences in TMS techniques in relation to stimulation intensity, stimulation
      length, brain areas stimulated and variations in the design of sham TMS all
      contributed to the heterogeneity of study findings and limited the interpretation
      and applicability of the results. In addition, the trials assessed their outcomes
      with a variety of scales, and usable data were limited. Therefore, to better
      evaluate the treatment effects of TMS in people with schizophrenia, we favour the
      use of standardised treatment protocols and outcome measures.

PMID- 26289588
TI  - Slow-release granisetron (APF530) versus palonosetron for chemotherapy-induced
      nausea/vomiting: analysis by American Society of Clinical Oncology emetogenicity
      criteria.
AB  - BACKGROUND: APF530 is a novel sustained-release formulation of granisetron. In a
      Phase III trial, APF530 500 mg was noninferior to palonosetron 0.25 mg in
      preventing acute chemotherapy-induced nausea and vomiting (CINV) after moderately
      (MEC) or highly emetogenic chemotherapy (HEC) and delayed CINV after MEC, but not
      superior in preventing delayed CINV after HEC. Emetogenicity was classified by
      Hesketh criteria; this reanalysis uses newer American Society of Clinical
      Oncology criteria. METHODS: Complete responses (no emesis or rescue medication)
      after cycle one were reanalyzed after reclassification of MEC and HEC by American
      Society of Clinical Oncology criteria. RESULTS: APF530 maintained noninferiority
      to palonosetron. CONCLUSION: Single-dose APF530 is a promising alternative to
      palonosetron for preventing acute and delayed CINV after MEC or HEC. The
      Clinicaltrials.gov identifier for this study is NCT00343460.

PMID- 26289587
TI  - Endogenous BDNF augments NMDA receptor phosphorylation in the spinal cord via
      PLCgamma, PKC, and PI3K/Akt pathways during colitis.
AB  - BACKGROUND: Spinal central sensitization is an important process in the
      generation and maintenance of visceral hypersensitivity. The release of brain
      derived neurotrophic factor (BDNF) from the primary afferent neurons to the
      spinal cord contributes to spinal neuronal plasticity and increases neuronal
      activity and synaptic efficacy. The N-Methyl-D-aspartic acid (NMDA) receptor
      possesses ion channel properties, and its activity is modulated by
      phosphorylation of its subunits including the NMDA receptor 1 (NR1). METHODS:
      Colonic inflammation was induced by a single dose of intracolonic instillation of
      tri-nitrobenzene sulfonic acid (TNBS). NR1 phosphorylation by BDNF in vivo and in
      culture was examined by western blot and immunohistochemistry. Signal
      transduction was studied by direct examination and use of specific inhibitors.
      RESULTS: During colitis, the level of NR1 phospho-Ser(896) was increased in the
      dorsal horn region of the L1 and S1 spinal cord; this increase was attenuated by
      injection of BDNF neutralizing antibody to colitic animals (36 MUg/kg,
      intravenous (i.v.)) and was also reduced in BDNF(+/-) rat treated with TNBS.
      Signal transduction examination showed that the extracellular signal-regulated
      kinase (ERK) activation was not involved in BDNF-induced NR1 phosphorylation. In
      contrast, the phosphatidylinositol 3-kinase (PI3K)/Akt pathway mediated BDNF
      induced NR1 phosphorylation in vivo and in culture; this is an additional pathway
      to the phospholipase C-gamma (PLCgamma) and the protein kinase C (PKC) that was
      widely considered to phosphorylate NR1 at Ser(896). In spinal cord culture, the
      inhibitors to PLC (U73122), PKC (bisindolylmaleimide I), and PI3K (LY294002), but
      not MEK (PD98059) blocked BDNF-induced NR1 phosphorylation. In animals with
      colitis, treatment with LY294002 (50 MUg/kg, i.v.) blocked the Akt activity as
      well as NR1 phosphorylation at Ser(896) in the spinal cord. CONCLUSION: BDNF
      participates in colitis-induced spinal central sensitization by up-regulating NR1
      phosphorylation at Ser(896). The PI3K/Akt pathway, in addition to PLCgamma and
      PKC, mediates BDNF action in the spinal cord during colitis.

PMID- 26289590
TI  - Brain-derived neurotrophic factor genetic polymorphism (rs6265) is protective
      against chemotherapy-associated cognitive impairment in patients with early-stage
      breast cancer.
AB  - BACKGROUND: Brain-derived neurotrophic factor (BDNF), a neurotrophin that
      regulates neuronal function and development, is implicated in several
      neurodegenerative conditions. Preliminary data suggest that a reduction of BDNF
      concentrations may lead to postchemotherapy cognitive impairment. We hypothesized
      that a single nucleotide polymorphism (rs6265) of the BDNF gene may predispose
      patients to cognitive impairment. This study aimed to evaluate the effect of BDNF
      gene polymorphism on chemotherapy-associated cognitive impairment. METHODS:
      Overall, 145 patients receiving chemotherapy for early-stage breast cancer (mean
      age: 50.8 +/- 8.8 y; 82.1% Chinese) were recruited. Patients' cognitive functions
      were assessed longitudinally using the validated Functional Assessment of Cancer
      Therapy-Cognitive Function (v.3) and an objective computerized tool, Headminder.
      Genotyping was performed using Sanger sequencing. Logistic regression was used to
      evaluate the association between BDNF Val66Met polymorphism and cognition after
      adjusting for ethnicity and clinically important covariates. RESULTS: Of the 145
      patients, 54 (37%) reported cognitive impairment postchemotherapy. The Met/Met
      genotype was associated with statistically significant lower odds of developing
      cognitive impairment (odds ratio [OR] = 0.26; 95% CI: 0.08-0.92; P = .036). The
      Met carriers were less likely to experience impairment in the domains of verbal
      fluency (OR = 0.34; 95% CI: 0.12-0.90; P = .031) and multitasking ability (OR =
      0.37; 95% CI: 0.15-0.91; P = .030) compared with the Val/Val homozygote. No
      associations were observed between Headminder and the BDNF Val66Met polymorphism.
      CONCLUSIONS: This is the first study to provide evidence that carriers of the
      BDNF Met allele are protected against chemotherapy-associated cognitive
      impairment. Further studies are required to validate the findings.

PMID- 26289589
TI  - Associations between the orexin (hypocretin) receptor 2 gene polymorphism
      Val308Ile and nicotine dependence in genome-wide and subsequent association
      studies.
AB  - BACKGROUND: Many genetic and environmental factors are involved in the etiology
      of nicotine dependence. Although several candidate gene variations have been
      reported by candidate gene studies or genome-wide association studies (GWASs) to
      be associated with smoking behavior and the vulnerability to nicotine dependence,
      such studies have been mostly conducted with subjects with European ancestry.
      However, genetic factors have rarely been investigated for the Japanese
      population as GWASs. To elucidate genetic factors involved in nicotine dependence
      in Japanese, the present study comprehensively explored genetic contributors to
      nicotine dependence by using whole-genome genotyping arrays with more than
      200,000 markers in Japanese subjects. RESULTS: The subjects for the GWAS and
      replication study were 148 and 374 patients, respectively. A two-stage GWAS was
      conducted using the Fagerstrom Test for Nicotine Dependence (FTND), Tobacco
      Dependence Screener (TDS), and number of cigarettes smoked per day (CPD) as
      indices of nicotine dependence. For the additional association analyses, patients
      who underwent major abdominal surgery, patients with methamphetamine
      dependence/psychosis, and healthy subjects with schizotypal personality trait
      data were recruited. Autopsy specimens with various diseases were also evaluated.
      After the study of associations between more than 200,000 marker single
      nucleotide polymorphisms (SNPs) and the FTND, TDS, and CPD, the nonsynonymous
      rs2653349 SNP (located on the gene that encodes orexin [hypocretin] receptor 2)
      was selected as the most notable SNP associated with FTND, with a p value of
      0.0005921 in the two-stage GWAS. This possible association was replicated for the
      remaining 374 samples. This SNP was also associated with postoperative pain, the
      initiation of methamphetamine use, schizotypal personality traits, and
      susceptibility to goiter. CONCLUSIONS: Although the p value did not reach a
      conventional genome-wide level of significance in our two-stage GWAS, we obtained
      significant results in the subsequent analyses that suggest that the rs2653349
      SNP (Val308Ile) could be a genetic factor that is related to nicotine dependence
      and possibly pain, schizotypal personality traits, and goiter in the Japanese
      population.

PMID- 26289592
TI  - The symptom burden of primary brain tumors: evidence for a core set of tumor- and
      treatment-related symptoms.
AB  - BACKGROUND: A set of symptoms common across cancers has been proposed to enhance
      quality of care and clinical research in solid tumor patients. Using data from
      several clinical studies, this study evaluated these symptoms in primary brain
      tumor patients. METHODS: Symptom report data using the MD Anderson Symptom
      Instrument -Brain Tumor (MDASI-BT) from 621 patients enrolled in 8 clinical
      studies was used. The prevalence and severity of symptoms were reported as they
      relate to tumor grade, treatment stage and KPS. RESULTS: The sample was primarily
      white (82.5%) males (59%) with high-grade gliomas (75%). More than 50% of
      patients reported at least 10 concurrent symptoms, and 40% of patients reporting
      having at least 3 moderate-to-severe symptoms. Fatigue, drowsiness, difficulty
      remembering, disturbed sleep, and distress were the most severe symptoms reported
      by all tumor grades. Functional interference of symptoms with ability to work,
      perform activities, walk, and enjoy life was reported by more than 25% of
      patients. CONCLUSIONS: These results support a core set of symptoms, common in
      other solid tumor patients, that may impact clinical care and assessment of
      treatment benefit. Although only 5 of the Center for Medical Technology Policy
      list of proposed core symptoms met criteria for inclusion in this sample, 5 of
      the other proposed core symptoms were also reported in similar frequency as
      reported in the other cancer populations. This primary brain tumor population
      differed from other solid tumor patients in that other symptoms, which could be
      disease related, were more prevalent and thus should also be collected for these
      patients.

PMID- 26289593
TI  - A cyclometallated fluorenyl Ir(iii) complex as a potential sensitiser for two
      photon excited photodynamic therapy (2PE-PDT).
AB  - A new Ir(iii) cyclometallated complex bearing a fluorenyl 5-substituted-1,10
      phenanthroline ligand ([Ir(ppy)2()][PF6], ppy = 2-phenylpyridine) is presented
      which exhibits enhanced triplet oxygen sensing properties. The efficacy of this
      complex to act as a photosensitiser for altering the morphology of C6 Glioma
      cells that represent malignant nervous tumours has been evaluated. The increased
      heavy metal effect and related spin-orbit coupling parameters on the
      photophysical properties of this complex are evidenced by comparison with Ru(ii)
      analogues. The complex [Ir(ppy)2()][PF6] is shown to exhibit relatively high two
      photon absorption efficiencies for the lowest energy MLCT electronic transitions
      with two-photon absorption cross sections that range from 50 to 80 Goeppert-Mayer
      units between 750 to 800 nm. Quantum yields for the complex were measured up to
      23% and the Stern-Volmer quenching constant, KSV was determined to be 40 bar(-1)
      in acetonitrile solution, confirming the high efficiency of the complex as a
      triplet oxygen sensitiser. Preliminary in vitro experiments with C6 Glioma cells
      treated with [Ir(ppy)2()][PF6], show that the complex is an efficient sensitizer
      for triplet oxygen, producing cytotoxic singlet oxygen ((1)O2) by two-photon
      excitation at 740 nm resulting in photodynamic effects that lead to localised
      cell damage and death. 

PMID- 26289591
TI  - Differentiating the mTOR inhibitors everolimus and sirolimus in the treatment of
      tuberous sclerosis complex.
AB  - Tuberous sclerosis complex (TSC) is a genetic autosomal dominant disorder
      characterized by benign tumor-like lesions, called hamartomas, in multiple organ
      systems, including the brain, skin, heart, kidneys, and lung. These hamartomas
      cause a diverse set of clinical problems based on their location and often result
      in epilepsy, learning difficulties, and behavioral problems. TSC is caused by
      mutations within the TSC1 or TSC2 genes that inactivate the genes' tumor
      suppressive function and drive hamartomatous cell growth. In normal cells, TSC1
      and TSC2 integrate growth signals and nutrient inputs to downregulate signaling
      to mammalian target of rapamycin (mTOR), an evolutionarily conserved serine
      threonine kinase that controls cell growth and cell survival. The molecular
      connection between TSC and mTOR led to the clinical use of allosteric mTOR
      inhibitors (sirolimus and everolimus) for the treatment of TSC. Everolimus is
      approved for subependymal giant cell astrocytomas and renal angiomyolipomas in
      patients with TSC. Sirolimus, though not approved for TSC, has undergone
      considerable investigation to treat various aspects of the disease. Everolimus
      and sirolimus selectively inhibit mTOR signaling with similar molecular
      mechanisms, but with distinct clinical profiles. This review differentiates mTOR
      inhibitors in TSC while describing the molecular mechanisms, pathogenic
      mutations, and clinical trial outcomes for managing TSC. 

PMID- 26289594
TI  - A first-in-human phase I and pharmacokinetic study of CP-4126 (CO-101), a
      nucleoside analogue, in patients with advanced solid tumours.
AB  - BACKGROUND: CP-4126 (gemcitabine elaidate, previously CO-101) is a lipid-drug
      conjugate of gemcitabine designed to circumvent human equilibrative nucleoside
      transporter1-related resistance to gemcitabine. The purpose of this study was to
      determine the maximum tolerated dose (MTD) and the recommended phase II dose
      (RP2D) of CP-4126, and to describe its pharmacokinetic profile. METHODS: Eligible
      patients with advanced refractory solid tumours, and adequate performance status,
      haematological, renal and hepatic function, were treated with one of escalating
      doses of CP-4126 administered by a 30-min intravenous infusion on days 1, 8 and
      15 of a 28-day cycle. Blood and urine samples were collected to determine the
      pharmacokinetics (PKs) of CP-4126. RESULTS: Forty-three patients, median age 59
      years (range 18-76; male = 27, female = 16), received one of ten dose levels (30
      1600 mg/m(2)). Dose-limiting toxicities included grade 3 anaemia, grade 3 fatigue
      and grade 3 elevation of transaminases. The MTD and RP2D were 1250 mg/m(2) on
      basis of the toxicity and PK data. CP-4126 followed dose-dependent kinetics and
      maximum plasma concentrations occurred at the end of CP-4126 infusion. Seven
      patients achieved stable disease sustained for >=3 months, including two patients
      with pancreatic cancer who had progressed on or after gemcitabine exposure.
      CONCLUSIONS: CP-4126 was well tolerated with comparable toxicity profile to
      gemcitabine. Future studies are required to determine its anti-tumour efficacy,
      either alone or in combination with other cytotoxic chemotherapy regimens.

PMID- 26289595
TI  - Juxta-articular adiposis dolorosa (Dercum's disease type IV): report of four
      cases and treatment by dermolipectomy.
AB  - Juxta-articular adiposis dolorosa is a rare subtype of Dercum's disease. It
      manifests mainly on the medial parts of the knees. Pain and impaired mobility are
      common symptoms. We report on four females (aged between 52 and 83 years) who
      suffered from juxta-articular adiposis dolorosa for more than 10 years. These
      patients were successfully treated by dermolipectomy resulting in dramatically
      improved pain and mobility. Adverse effects and complications were minor with a
      lymph fistula in a single patient which was treated by surgery. 

PMID- 26289597
TI  - The metabolic and temporal basis of muscle hypertrophy in response to resistance
      exercise.
AB  - Constituting ~40% of body mass, skeletal muscle has essential locomotory and
      metabolic functions. As such, an insight into the control of muscle mass is of
      great importance for maintaining health and quality-of-life into older age, under
      conditions of cachectic disease and with rehabilitation. In healthy weight
      bearing individuals, muscle mass is maintained by the equilibrium between muscle
      protein synthesis (MPS) and muscle protein breakdown; when this balance tips in
      favour of MPS hypertrophy occurs. Despite considerable research into
      pharmacological/nutraceutical interventions, resistance exercise training (RE-T)
      remains the most potent stimulator of MPS and hypertrophy (in the majority of
      individuals). However, the mechanism(s) and time course of hypertrophic responses
      to RE-T remain poorly understood. We would suggest that available data are very
      much in favour of the notion that the majority of hypertrophy occurs in the early
      phases of RE-T (though still controversial to some) and that, for the most part,
      continued gains are hard to come by. Whilst the mechanisms of muscle hypertrophy
      represent the culmination of mechanical, auto/paracrine and endocrine events, the
      measurement of MPS remains a cornerstone for understanding the control of
      hypertrophy - mainly because it is the underlying driving force behind skeletal
      muscle hypertrophy. Development of sophisticated isotopic techniques (i.e.
      deuterium oxide) that lend to longer term insight into the control of hypertrophy
      by sustained RE-T will be paramount in providing insights into the metabolic and
      temporal regulation of hypertrophy. Such technologies will have broad application
      in muscle mass intervention for both athletes and for mitigating disease/age
      related cachexia and sarcopenia, alike. 

PMID- 26289596
TI  - Smoking, inflammation and small cell lung cancer: recent developments.
AB  - Small cell lung cancer (SCLC) accounts for 15 % of all lung tumors and represents
      an invasive neuroendocrine malignancy with poor survival rates. This cancer is
      highly prevalent in smokers and characterized by inactivation of p53 and
      retinoblastoma. First in vitro expansion of circulating tumor cells (CTCs) of
      SCLC patients allowed for investigation of the cell biology of tumor
      dissemination. In the suggested CTC SCLC model, the primary tumor attracts and
      educates tumor-promoting and immunosuppressive macrophages which in turn arm CTCs
      to spread and generate distal lesions. Preexisting inflammatory processes
      associated with chronic obstructive pulmonary disease (COPD) seem to potentiate
      the subsequent activity of tumor-associated macrophages (TAM). Activation of
      signal transducer and activator of transcription 3 (STAT3) and expression of
      chitinase-3-like 1/YKL-40 in SCLC CTCs seems to be associated with drug
      resistance. In conclusion, inflammation-associated generation of invasive and
      chemoresistant CTCs most likely explains the characteristic features of SCLC,
      namely early dissemination and rapid failure of chemotherapy. 

PMID- 26289598
TI  - Seismic monitoring in the oceans by autonomous floats.
AB  - Our understanding of the internal dynamics of the Earth is largely based on
      images of seismic velocity variations in the mantle obtained with global
      tomography. However, our ability to image the mantle is severely hampered by a
      lack of seismic data collected in marine areas. Here we report observations made
      under different noise conditions (in the Mediterranean Sea, the Indian and
      Pacific Oceans) by a submarine floating seismograph, and show that such floats
      are able to fill the oceanic data gap. Depending on the ambient noise level, the
      floats can record between 35 and 63% of distant earthquakes with a moment
      magnitude M>=6.5. Even magnitudes <6.0 can be successfully observed under
      favourable noise conditions. The serendipitous recording of an earthquake swarm
      near the Indian Ocean triple junction enabled us to establish a threshold
      magnitude between 2.7 and 3.4 for local earthquakes in the noisiest of the three
      environments. 

PMID- 26289600
TI  - The Roles of Tight Junctions and Claudin-1 in the Microbubble-Mediated Ultrasound
      Induced Enhancement of Drug Concentrations in Rat Prostate.
AB  - Although microbubble-mediated ultrasound irradiation can enhance the prostate
      permeability, little is known about the mechanism. In our study, the healthy,
      adult male SD rats were divided into four groups: the BC, US, MB, and MMUS
      groups. A therapeutic ultrasound apparatus was used to treat the rats prostates
      in the presence of circulating MBs. Cefuroxime was injected to assess prostate
      permeability by HPLC. The structures of prostate tissues and TJs were observed by
      light and transmission electron microscopy. Western blot was used to assess
      claudin-1 expression. After treatment of microbubble-mediated ultrasound
      irradiation, the cefuroxime concentrations in the prostate were significantly
      increased. HE staining demonstrated that the gland epithelial cell layer became
      dropsical, thick, and disordered. In transmission electron microscopy, the TJs
      between adjacent capillary endothelial cells or gland epithelial cells were
      disjointed and partly interrupted. Furthermore, western blot showed the
      expression of claudin-1 was significantly decreased. However, these findings were
      not observed in the prostates exposed to microbubble or ultrasound alone, as well
      as the healthy control rats. In conclusion, microbubble-mediated ultrasound
      irradiation significantly enhanced the prostate permeability and improve the
      cefuroxime concentrations in prostate. The changes in TJs structure and the
      decreased claudin-1 expression may play important roles in this process.

PMID- 26289601
TI  - Differentiating virulent 027 and non-027 Clostridium difficile strains by
      molecular methods.
AB  - OBJECTIVE: Hypervirulent Clostridium difficile clade has been shown to include
      several lineages of ribotype 027 and also other ribotypes. We present data on
      additional non-027 strains, identified as presumptive 027 by two commercial
      molecular C. difficile assays. METHODS: The tested clinical isolates were
      selected from the national reference laboratory collection on the basis of toxin
      gene profile similarities with ribotype 027 and tested with XpertC. difficile/Epi
      and Amplidiag C. difficile+027 assay. RESULT: Xpert misclassified five ribotypes
      (016, 019, 080, 176 and variant of type 046) as presumptive 027 and Amplidiag two
      ribotypes (016, 176). The misclassified strains were rare, covering 1.6% of
      reference laboratory strain collection. CONCLUSION: Our findings confirm the
      concept that there are closely related outliers to hypervirulent 027 clones that
      can be misclassified as 027, and that these comprise numerous ribotypes,
      including previously reported four ribotypes (198, 176, 244, 019), and additional
      three (016, v046, 080) identified in the present study.

PMID- 26289599
TI  - Ouabain Regulates CFTR-Mediated Anion Secretion and Na,K-ATPase Transport in
      ADPKD Cells.
AB  - Cyst enlargement in autosomal dominant polycystic kidney disease (ADPKD) requires
      the transepithelial secretion of fluid into the cyst lumen. We previously showed
      that physiological amounts of ouabain enhance cAMP-dependent fluid secretion and
      cyst growth of human ADPKD cyst epithelial cells in culture and formation of cyst
      like dilations in metanephric kidneys from Pkd1 mutant mice. Here, we
      investigated the mechanisms by which ouabain promotes cAMP-dependent fluid
      secretion and cystogenesis. Ouabain (3 nM) enhanced cAMP-induced cyst-like
      dilations in embryonic kidneys from Pkd1 (m1Bei) mice, but had no effect on
      metanephroi from Pkd1 (m1Bei) mice that lack expression of the cystic fibrosis
      transmembrane conductance regulator (CFTR). Similarly, ouabain stimulation of
      cAMP-induced fluid secretion and in vitro cyst growth of ADPKD cells were
      abrogated by CFTR inhibition, showing that CFTR is required for ouabain effects
      on ADPKD fluid secretion. Moreover, ouabain directly enhanced the cAMP-dependent
      Cl(-) efflux mediated by CFTR in ADPKD monolayers. Ouabain increased the
      trafficking of CFTR to the plasma membrane and up-regulated the expression of the
      CFTR activator PDZK1. Finally, ouabain decreased plasma membrane expression and
      activity of the Na,K-ATPase in ADPKD cells. Altogether, these results show that
      ouabain enhances net fluid secretion and cyst formation by activating apical
      anion secretion via CFTR and decreasing basolateral Na(+) transport via Na,K
      ATPase. These results provide new information on the mechanisms by which ouabain
      affects ADPKD cells and further highlight the importance of ouabain as a non
      genomic stimulator of cystogenesis in ADPKD.

PMID- 26289604
TI  - Exercise for adolescents with depression: valued aspects and perceived change.
AB  - INTRODUCTION: Despite systematic reviews demonstrating an association between
      exercise participation and reduced depressive symptoms in young people, there is
      no qualitative research exploring the experience of depressed adolescents who
      have engaged in an exercise intervention. AIMS: To explore the experience of
      depressed adolescents who had recently engaged in a preferred intensity exercise
      intervention. METHOD: The participants (n = 26) were recruited through health and
      social care services, were all in treatment for depression, and were purposefully
      sampled for interview following engagement in a preferred intensity exercise
      intervention, which was being evaluated via a pragmatic randomized controlled
      trial. A thematic approach was undertaken to analyse and organize the data.
      RESULTS: Numerous beneficial changes were reported by participants alongside
      specific aspects of the intervention that were valued. DISCUSSION AND
      IMPLICATIONS: The findings suggest that preferred intensity exercise can lead to
      feelings of improved mood, enjoyment and achievement, alongside benefits that
      transcend depressive symptom reduction. Considering mental health nurses are in
      key positions to promote exercise in this population, the current findings
      provide vital information for this purpose.

PMID- 26289603
TI  - Recent developments in multiplexing techniques for immunohistochemistry.
AB  - Methods to detect immunolabeled molecules at increasingly higher resolutions,
      even when present at low levels, are revolutionizing immunohistochemistry (IHC).
      These technologies can be valuable for the management and examination of rare
      patient tissue specimens, and for improved accuracy of early disease detection.
      The purpose of this article is to highlight recent multiplexing methods that are
      candidates for more prevalent use in clinical research and potential translation
      to the clinic. Multiplex IHC methods, which permit identification of at least 3
      and up to 30 discrete antigens, have been divided into whole-section staining and
      spatially-patterned staining categories. Associated signal enhancement
      technologies that can enhance performance and throughput of multiplex IHC assays
      are also discussed. Each multiplex IHC technique, detailed herein, is associated
      with several advantages as well as tradeoffs that must be taken into
      consideration for proper evaluation and use of the methods. 

PMID- 26289611
TI  - Novel Carbazol-Pyridine-Carbonitrile Derivative as Excellent Blue Thermally
      Activated Delayed Fluorescence Emitter for Highly Efficient Organic Light
      Emitting Devices.
AB  - A novel blue thermally activated delayed fluorescence (TADF) emitter, CPC (2,6
      di(9H-carbazol-9-yl)-4-phenylpyridine-3,5-dicarbonitrile), was designed and
      synthesized. By directly linking carbazole (to serve as electron-donor) and
      pyridine-3,5-dicarbonitrile (to serve as electron-acceptor), and distributing
      cyanogroups and carbazole groups at the para-position of pyridine core, CPC
      successfully achieves an extremely small singlet-triplet splitting and fairish
      photoluminescence quantum yield, thus can act as the highly efficient blue TADF
      emitter. The optimized organic light-emitting diode (OLED) based on 13 wt % CPC
      doped in mCP (1,3-bis(9H-carbazol-9-yl)benzene) host exhibits maximum current
      efficiency, power efficiency, and external quantum efficiency of 47.7 cd A(-1),
      42.8 lm W(-1), and 21.2%, respectively, which are the best results in reported
      blue TADF-based devices up to date and even comparable with the best reported
      blue phosphorescent OLEDs. 

PMID- 26289602
TI  - The potential of tumor-derived exosomes for noninvasive cancer monitoring.
AB  - Tumor-derived exosomes (TEX) are emerging as a new type of cancer biomarker. TEX
      are membrane-bound, virus-size vesicles of endocytic origin present in all body
      fluids of cancer patients. Based on the expanding albeit incomplete knowledge of
      their biogenesis, secretion by tumor cells and cancer cell-specific molecular and
      genetic contents, TEX are viewed as promising, clinically-relevant surrogates of
      cancer progression and response to therapy. Preliminary proteomic, genetic and
      functional profiling of tumor cell-derived or cancer plasma-derived exosomes
      confirms their unique characteristics. Alterations in protein or nucleic acid
      profiles of exosomes in plasma of cancer patients responding to therapies appear
      to correlate with clinical endpoints. However, methods for TEX isolation and
      separation from the bulk of human plasma-derived exosomes are not yet established
      and their role as biomarkers remains to be confirmed. Further development and
      validation of TEX as noninvasive, liquid equivalents of tumor biopsies are
      necessary to move this effort forward. 

PMID- 26289612
TI  - Phosphodiesterase Isoform Regulation of Cell Proliferation and Fluid Secretion in
      Autosomal Dominant Polycystic Kidney Disease.
AB  - cAMP stimulates cell proliferation and Cl(-)-dependent fluid secretion, promoting
      the progressive enlargement of renal cysts in autosomal dominant polycystic
      kidney disease (ADPKD). Intracellular cAMP levels are determined by the balance
      of cAMP synthesis by adenylyl cyclases and degradation by phosphodiesterases
      (PDEs). Therefore, PDE isoform expression and activity strongly influence global
      and compartmentalized cAMP levels. We report here that PDE3 and PDE4 expression
      levels are lower in human ADPKD tissue and cells compared with those of normal
      human kidneys (NHKs), whereas PDE1 levels are not significantly different.
      Inhibition of PDE4 caused a greater increase in basal and vasopressin (AVP)
      stimulated cAMP levels and Cl(-) secretion by ADPKD cells than inhibition of
      PDE1, and inhibition of PDE4 induced cyst-like dilations in cultured mouse Pkd1(
      /-) embryonic kidneys. In contrast, inhibition of PDE1 caused greater stimulation
      of extracellular signal-regulated kinase (ERK) and proliferation of ADPKD cells
      than inhibition of PDE4, and inhibition of PDE1 enhanced AVP-induced ERK
      activation. Notably, inhibition of PDE1, the only family of Ca(2+)-regulated
      PDEs, also induced a mitogenic response to AVP in NHK cells, similar to the
      effect of restricting intracellular Ca(2+). PDE1 coimmunoprecipitated with B-Raf
      and A-kinase anchoring protein 79, and AVP increased this interaction in ADPKD
      but not NHK cells. These data suggest that whereas PDE4 is the major PDE isoform
      involved in the regulation of global intracellular cAMP and Cl(-) secretion, PDE1
      specifically affects the cAMP signal to the B-Raf/MEK/ERK pathway and regulates
      AVP-induced proliferation of ADPKD cells.

PMID- 26289613
TI  - Impact of long-term use of eHealth systems in adolescents with type 1 diabetes
      treated with sensor-augmented pump therapy.
AB  - Telemedicine in diabetes includes telemonitoring and transmission of important
      data (self monitoring of blood glucose data, insulin therapy, pump setting, etc.)
      from the patient s home to the diabetic unit, with a real-time health feedback.
      Moreover, an eHealth approach is thought to facilitate diabetes management and to
      improve compliance to CSII/SAP treatment in adolescents, but to date, limited
      literature related to this topic is available and long-term studies are still
      lacking. The main aim of this study was to compare the long-term effect on
      glycometabolic control of eHealth intervention and traditional care in T1DM SAP
      treated adolescents. In our study we demonstrated a favorable impact of monthly
      teleassistance on treatment compliance. Adolescents receiving frequent feedback
      provided by the medicalmultidisciplinary team, due to the telemonitoring,
      resulted more compliant in self-management of diabetes. In particular, the
      medical team feedback resulted in interventions on behavioral errors and insulin
      therapy adjustments, leading to an improved glycometabolic control. 

PMID- 26289614
TI  - The Kidney in Pediatric Liver Disease.
AB  - There is an intricate relationship between the liver and the kidney, with renal
      physiology and function intimately involved in many primary disorders of
      pediatric liver disease. The hemodynamic changes of progressive cirrhosis affect
      and are directly affected by changes in renal blood flow and renal handling of
      sodium and free water excretion. Resulting complications of worsening ascites,
      hyponatremia, and acute kidney injury frequently complicate the care of children
      with advanced liver disease and contribute significant morbidity and mortality.
      While liver transplantation may restore hemodynamic stability, nearly 40% of
      pediatric liver transplant recipients develop chronic kidney disease post
      transplant and approximately 25% are left with clinical hypertension. This review
      seeks to provide a basic understanding of this relationship to enable the
      provision of optimal care to children with liver disease.

PMID- 26289615
TI  - Dangers of Prehospital Cooling: A Case Report of Afterdrop in a Patient with
      Exertional Heat Stroke.
AB  - BACKGROUND: Exertional heat stroke is a potentially life-threatening disease with
      varying clinical presentations and severity. Given the severe morbidity that can
      accompany the disease, the immediate management often begins in the prehospital
      setting. It is important to have not only a comprehensive understanding of the
      prehospital cooling methods in addition to hospital management strategies, but an
      understanding of their potential complications as well. CASE REPORT: A 32-year
      old male presented to a San Antonio hospital in March 2014 with progressive
      confusion, nausea, nonbloody emesis, and ataxia. Initial presentation was
      concerning for exertional heat stroke, as the patient was recorded in the field
      to have a temperature of 42.1 degrees C (106.2 degrees F). The patient, on
      arrival to the emergency department, was found to have a core body temperature of
      38.1 degrees C (100.6 degrees F). All active cooling measures were terminated and
      active rewarming was initiated. Despite adequate resuscitation and rapid
      identification of the patient's overcorrection in core body temperature, the
      lowest recorded temperature was 36.0 degrees C (96.8 degrees F). Why Should an
      Emergency Physician Be Aware of This? This case represents the dangers associated
      with exertional heat stroke, overcorrection of core body temperature, and the
      potentially lethal complication of afterdrop. It also represents the need for
      immediate recognition of the condition and initiation of appropriate medical
      care. Although this patient's clinical outcome was good, the event could have
      caused serious morbidity or could have potentially been fatal.

PMID- 26289616
TI  - Correction: Comparison of the reactivity of beta-thiolactones and beta-lactones
      toward ring-opening by thiols and amines.
AB  - Correction for 'Comparison of the reactivity of beta-thiolactones and beta
      lactones toward ring-opening by thiols and amines' by Amandine Noel et al., Org.
      Biomol. Chem., 2012, 10, 6480-6483. 

PMID- 26289617
TI  - Warping of the levator hiatus: how significant is it?
AB  - OBJECTIVES: The levator hiatus is the largest potential hernial portal in the
      human body. Excessive distensibility is associated with female pelvic organ
      prolapse (POP). Distension occurs not just laterally but also caudally, resulting
      in perineal descent and hiatal deformation or 'warping'. The aim of this study
      was to quantify the warping effect in symptomatic women, to validate the depth of
      the rendered volume used for the 'simplified method' of measuring hiatal
      dimensions and to determine predictors for the degree of warping. METHODS: This
      was a retrospective study utilizing records of patients referred to a tertiary
      urogynecological service between November 2012 and March 2013. Patients underwent
      a standardized interview, clinical assessment using the POP quantification system
      of the International Continence Society and four-dimensional translabial
      ultrasound. The craniocaudal difference in the location of minimal distances in
      mid-sagittal and coronal planes was determined by offline analysis of ultrasound
      volumes, and provided a numerical measure of warping. We tested potential
      predictors, such as demographic factors, signs and symptoms of prolapse, levator
      avulsion and levator distensibility, for an association with warping. RESULTS:
      Full datasets were available for 190 women. The mean craniocaudal difference in
      location of minimal distances in mid-sagittal and coronal planes was -1.26 mm
      (range, -6.7 to 4.6 mm; P < 0.001). This measure of warping was associated with
      hiatal area on Valsalva maneuver (r = - 0.284; P < 0.0001) and signs of
      significant prolapse on clinical and ultrasound examination (both P < 0.0001).
      CONCLUSIONS: The plane of minimal dimensions of the levator ani hiatus is non
      Euclidean, i.e. warped, and the degree of warping is associated with hiatal
      distension, or 'ballooning', and with POP. However, the degree of warping is
      minor, the largest difference we found in the location of the plane of minimal
      dimensions being 6.7 mm. Hence, our results support the determination of hiatal
      area in a rendered volume of 1-2 cm in depth. Copyright (c) 2015 ISUOG. Published
      by John Wiley & Sons Ltd.

PMID- 26289618
TI  - MUCT-Based Analysis of the Solid Phase in Foams: Cell Wall Corrugation and other
      Microscopic Features.
AB  - This work presents a series of three-dimensional computational methods with the
      objective of analyzing and quantifying some important structural characteristics
      in a collection of low-density polyolefin-based foams. First, the solid phase
      tortuosity, local thickness, and surface curvature, have been determined over the
      solid phase of the foam. These parameters were used to quantify the presence of
      wrinkles located at the cell walls of the foams under study. In addition, a novel
      segmentation technique has been applied to the continuous solid phase. This novel
      method allows performing a separate analysis of the constituting elements of this
      phase, that is, cell struts and cell walls. The methodology is based on a solid
      classification algorithm and evaluates the local topological dissimilarities
      existing between these elements. Thanks to this method it was possible to perform
      a separate analysis of curvature, local thickness, and corrugation ratio in the
      solid constituents that reveals additional differences that were not detected in
      the first analysis of the continuous structure. The methods developed in this
      work are applicable to other types of porous materials in fields such as
      geoscience or biomedicine. 

PMID- 26289620
TI  - New Sustainable Model of Biorefineries: Biofactories and Challenges of
      Integrating Bio- and Solar Refineries.
AB  - The new scenario for sustainable (low-carbon) chemical and energy production
      drives the development of new biorefinery concepts (indicated as biofactories)
      with chemical production at the core, but flexible and small-scale production. An
      important element is also the integration of solar energy and CO2 use within
      biobased production. This concept paper, after shortly introducing the motivation
      and recent trends in this area, particularly at the industrial scale, and some of
      the possible models (olefin and intermediate/high-added-value chemicals
      production), discusses the opportunities and needs for research to address the
      challenge of integrating bio- and solar refineries. Aspects discussed regard the
      use of microalgae and CO2 valorization in biorefineries/biofactories by chemo- or
      biocatalysis, including possibilities for their synergetic cooperation and
      symbiosis, as well as integration within the agroenergy value chain.

PMID- 26289619
TI  - Avenanthramide supplementation attenuates eccentric exercise-inflicted blood
      inflammatory markers in women.
AB  - PURPOSE: Rigorous exercise is known to generate reactive oxygen species (ROS) and
      inflict inflammatory response. The present study investigated whether dietary
      supplementation of avenanthramides (AVA) in oats would increase antioxidant
      protection and reduce inflammation in humans after an acute bout of eccentric
      exercise. METHODS: Young women (age 18-30 years, N = 16) were randomly divided
      into two groups in a double-blinded fashion, receiving two cookies made of oat
      flour providing 9.2 mg AVA (AVA) or 0.4 mg AVA (Control, C) each day for 8 weeks.
      Before and after the dietary regimen each group of subjects ran downhill (DR) on
      a treadmill at -9% grade for 1 h at a speed to elicit 75% of maximal heart rate.
      Blood samples were collected at rest, immediately and 24 h post-DR. RESULTS:
      Before dietary supplementation plasma creatine kinase activity and tumor necrosis
      factor (TNF)-alpha concentration were increased immediately after DR (P < 0.05),
      whereas neutrophil respiratory burst (NRB) was elevated 24 h post-DR (P < 0.05).
      CK and TNF-alpha response to DR was abolished during post-supplementation tests
      in both AVA and C groups, whereas NRB was blunted only in AVA but not in C.
      Plasma interleukin-6 level and mononuclear cell nuclear factor (NF) kappaB
      activity were not affected by DR either before or after dietary supplementation,
      but were lowered 24 h post-DR in AVA versus C (P < 0.05). Both groups increased
      plasma total antioxidant activity following 8-week dietary regimen (P < 0.05),
      whereas only AVA group increased resting plasma glutathione (GSH) concentration
      (P < 0.05), decreased glutathione disulfide response to DR, and lowered
      erythrocyte GSH peroxidase activity (P < 0.05). CONCLUSIONS: Our data of pre- and
      post-supplementation difference reflect an interaction between repeated measure
      effect of eccentric exercise and AVA in diet. Long-term AVA supplementation can
      attenuate blood inflammation markers, decrease ROS generation and NFkB
      activation, and increased antioxidant capacity during an eccentric exercise bout.

PMID- 26289621
TI  - Electronic control of coherence in a two-dimensional array of photonic crystal
      surface emitting lasers.
AB  - We demonstrate a semiconductor PCSEL array that uniquely combines an in-plane
      waveguide structure with nano-scale patterned PCSEL elements. This novel geometry
      allows two-dimensional electronically controllable coherent coupling of remote
      vertically emitting lasers. Mutual coherence of the PCSEL elements is verified
      through the demonstration of a two-dimensional Young's Slits experiment. In
      addition to allowing the all-electronic control of the interference pattern, this
      type of device offers new routes to power and brightness scaling in semiconductor
      lasers, and opportunities for all-electronic beam steering. 

PMID- 26289622
TI  - Nanoparticle cluster gas sensor: Pt activated SnO2 nanoparticles for NH3
      detection with ultrahigh sensitivity.
AB  - Pt activated SnO2 nanoparticle clusters were synthesized by a simple solvothermal
      method. The structure, morphology, chemical state and specific surface area were
      analyzed by X-ray powder diffraction (XRD), transmission electron microscopy
      (TEM), X-ray photoelectron spectroscopy (XPS) and N2-sorption studies,
      respectively. The SnO2 nanoparticle cluster matrix consists of tens of thousands
      of SnO2 nanoparticles with an ultra-small grain size estimated to be 3.0 nm. And
      there are abundant random-packed wormhole-like pores, caused by the inter
      connection of the SnO2 nanoparticles, throughout each cluster. The platinum
      element is present in two forms including metal (Pt) and tetravalent metal oxide
      (PtO2) in the Pt activated SnO2 nanoparticle clusters. The as-synthesized pure
      and Pt activated SnO2 nanoparticle clusters were used to fabricate gas sensor
      devices. It was found that the gas response toward 500 ppm of ammonia was
      improved from 6.48 to 203.44 through the activation by Pt. And the results
      indicate that the sensor based on Pt activated SnO2 not only has ultrahigh
      sensitivity but also possesses good response-recovery properties, linear
      dependence, repeatability, selectivity and long-term stability, demonstrating the
      potential to use Pt activated SnO2 nanoparticle clusters as ammonia gas sensors.
      At the same time, the formation mechanisms of the unique nanoparticle clusters
      and highly enhanced sensitivity are also discussed. 

PMID- 26289624
TI  - Outcomes for liver transplant candidates listed with low model for end-stage
      liver disease score.
AB  - The Model for End-Stage Liver Disease (MELD) score, which estimates mortality
      within 90 days, determines priority for liver transplantation (LT). However,
      longer-term outcomes on the wait list for patients who are initially listed with
      low MELD scores are not well characterized. All adults listed for primary LT at a
      single, high-volume center from 2005 to 2012 with an initial laboratory MELD
      score of 22 or lower were evaluated. Excluded were those patients listed with
      MELD exception points who underwent living donor liver transplantation (LDLT) or
      transplantation at another center, or who were removed from the wait list for
      nonmedical reasons. Outcomes and causes of death were identified by United
      Network for Organ Sharing, the National Death Index, and an electronic medical
      record review. Multivariate competing risk analysis evaluated predictors of death
      compared to deceased donor liver transplantation (DDLT); 893 patients were listed
      from 2005 to 2012. By the end of follow-up, 27% had undergone DDLT, and 31% were
      removed from the wait list for death or clinical deterioration. In a competing
      risks assessment, only MELD score of 6-9, older age, lower serum albumin, lower
      body mass index, and diabetes conferred an increased risk of wait-list dropout
      compared to DDLT. Listing for simultaneous liver-kidney transplantation was
      protective against wait-list dropout. Of the patients included, 275 patients died
      or were delisted for being too sick; 87% of the identifiable causes of death were
      directly related to end-stage liver disease or hepatocellular carcinoma. In
      conclusion, patients with low listing MELD scores remain at a significant risk
      for death due to liver-related causes and may benefit from early access to
      transplantation, such as LDLT or acceptance of high-risk donor livers. Predictors
      of death compared to transplantation may allow for early identification of
      patients who are at risk for wait-list mortality.

PMID- 26289625
TI  - Blood Smear Image Based Malaria Parasite and Infected-Erythrocyte Detection and
      Segmentation.
AB  - In this study, an automatic malaria parasite detector is proposed to perceive the
      malaria-infected erythrocytes in a blood smear image and to separate parasites
      from the infected erythrocytes. The detector hence can verify whether a patient
      is infected with malaria. It could more objectively and efficiently help a doctor
      in diagnosing malaria. The experimental results show that the proposed method can
      provide impressive performance in segmenting the malaria-infected erythrocytes
      and the parasites from a blood smear image taken under a microscope. This paper
      also presents a weighted Sobel operation to compute the image gradient. The
      experimental results demonstrates that the weighted Sobel operation can provide
      more clear-cut and thinner object contours in object segmentation. 

PMID- 26289626
TI  - Towards Context-Aware and User-Centered Analysis in Assistive Environments: A
      Methodology and a Software Tool.
AB  - One of the main challenges on Ambient Assisted Living (AAL) is to reach an
      appropriate acceptance level of the assistive systems, as well as to analyze and
      monitor end user tasks in a feasible and efficient way. The development and
      evaluation of AAL solutions based on user-centered perspective help to achive
      these goals. In this work, we have designed a methodology to integrate and
      develop analytics user-centered tools into assistive systems. An analysis
      software tool gathers information of end users from adapted psychological
      questionnaires and naturalistic observation of their own context. The aim is to
      enable an in-deep analysis focused on improving the life quality of elderly
      people and their caregivers. 

PMID- 26289627
TI  - Introducing E-learning in Epidemiology Course for Undergraduate Medical Students
      at the Faculty of Medicine, University of Belgrade: A Pilot Study.
AB  - The aim of this study was to determine whether e-learning as a new teaching
      concept was acceptable for second-year undergraduates and to compare attitudes
      and exam results of students who followed electronic compared with classroom
      seminars. The electronic seminars (e-seminars) were developed several months
      prior to start of the epidemiology course for second-year students at the Faculty
      of Medicine, University of Belgrade. The students who applied for e-seminars
      accessed their content during summer semester (February-May) 2014. E-seminars
      were set according to the existing topics in practical workbook and designed
      using Moodle, a free, open-source, personal home page web application for
      producing modular internet-based courses. To evaluate the motives for enrollment
      and satisfaction with seminars, two surveys (pre- and post-course) were
      administered. Students' exam grades were registered over 4 exam sessions (June
      October 2014) and compared according to seminar program. Out of 516 students in
      the second year, 60 (11.6 %) applied for e-seminars (mean age 21 years). Students
      considered the reason "It's easier to do assignments from home" as the strongest
      motive to participate. When compared to classroom seminars, students in e
      seminars had significantly more fun (p = 0.003), thought that e-seminars were
      better mode to learn epidemiology (p = 0.030) and would recommend them to other
      colleagues (p = 0.001). There was no significant difference in average grade
      received at the oral exam in epidemiology (t = 0.071, p = 0.944). E-seminars in
      undergraduate epidemiology course add a novel, easy-to-follow and amusing mode of
      learning. Based on this pilot study, e-seminars in epidemiology will be available
      for next generations of students, while further improvement of e-seminars could
      include expansion of seminar syllabus and development of discussion fora.

PMID- 26289628
TI  - Classification of Medical Datasets Using SVMs with Hybrid Evolutionary Algorithms
      Based on Endocrine-Based Particle Swarm Optimization and Artificial Bee Colony
      Algorithms.
AB  - The classification and analysis of data is an important issue in today's
      research. Selecting a suitable set of features makes it possible to classify an
      enormous quantity of data quickly and efficiently. Feature selection is generally
      viewed as a problem of feature subset selection, such as combination optimization
      problems. Evolutionary algorithms using random search methods have proven highly
      effective in obtaining solutions to problems of optimization in a diversity of
      applications. In this study, we developed a hybrid evolutionary algorithm based
      on endocrine-based particle swarm optimization (EPSO) and artificial bee colony
      (ABC) algorithms in conjunction with a support vector machine (SVM) for the
      selection of optimal feature subsets for the classification of datasets. The
      results of experiments using specific UCI medical datasets demonstrate that the
      accuracy of the proposed hybrid evolutionary algorithm is superior to that of
      basic PSO, EPSO and ABC algorithms, with regard to classification accuracy using
      subsets with a reduced number of features. 

PMID- 26289629
TI  - Design of a Computer-Assisted System to Automatically Detect Cell Types Using ANA
      IIF Images for the Diagnosis of Autoimmune Diseases.
AB  - Indirect immunofluorescence technique applied on HEp-2 cell substrates provides
      the major screening method to detect ANA patterns in the diagnosis of autoimmune
      diseases. Currently, the ANA patterns are mostly inspected by experienced
      physicians to identify abnormal cell patterns. The objective of this study is to
      design a computer-assisted system to automatically detect cell patterns of IIF
      images for the diagnosis of autoimmune diseases in the clinical setting. The
      system simulates the functions of modern flow cytometer and provides the
      diagnostic reports generated by the system to the technicians and physicians
      through the radar graphs, box-plots, and tables. The experimental results show
      that, among the IIF images collected from 17 patients, 6 were classified as
      coarse-speckled, 3 as diffused, 2 as discrete-speckled, 1 as fine-speckled, 2 as
      nucleolar, and 3 as peripheral patterns, which were consistent with the patterns
      determined by the physicians. In addition to recognition of cell patterns, the
      system also provides the function to automatically generate the report for each
      patient. The time needed for the whole procedure is less than 30 min, which is
      more efficient than the manual operation of the physician after inspecting the
      ANA IIF images. Besides, the system can be easily deployed on many desktop and
      laptop computers. In conclusion, the designed system, containing functions for
      automatic detection of ANA cell pattern and generation of diagnostic report, is
      effective and efficient to assist physicians to diagnose patients with autoimmune
      diseases. The limitations of the current developed system include (1) only a
      unique cell pattern was considered for the IIF images collected from a patient,
      and (2) the cells during the process of mitosis were not adopted for cell
      classification.

PMID- 26289630
TI  - A Rare Case of Laparoscopic Repair of Simultaneously Occurring Morgagni and
      Paraesophageal Hernias.
AB  - Simultaneously occurring Morgagni hernia and paraesophageal hernia is an
      extremely rare clinical condition with only six case reports in the English
      language literature and only two laparoscopic repair reports. We report a 73-year
      old woman with both Morgagni hernia and paraesophageal hernia who underwent
      successful laparoscopic repair of the hernia defects using transabdominal wall
      suturing. The laparoscopic operation can provide excellent exposure and repair
      the hernia defect easily with minimal invasiveness and fewer complications. This
      case report reported the concurring Morgagni and paraesophageal hernias and
      validated the feasibility of laparoscopic repair both hernias simultaneously. 

PMID- 26289631
TI  - Prognostic Factors for Survival after Resection of Pulmonary Metastases from
      Colorectal Carcinoma.
AB  - PURPOSE: As chemotherapy has improved, the survival of patients with metastatic
      colorectal carcinoma has reached up to 2.5 years. Many of these patients
      experience pulmonary metastases; however, the prognosis after pulmonary
      metastasectomy is not satisfying. In this study, we analyzed the prognostic
      factors for survival in patients who underwent pulmonary metastasectomy. METHODS:
      Eighty-seven patients with colorectal carcinoma received pulmonary
      metastasectomy. The pathological status of the primary tumor, outcome of the
      pulmonary metastasectomy, disease-free interval, perioperative carcinoembryonic
      antigen (CEA) level and history of liver metastases were assessed. RESULTS: The
      five-year survival was 42.5% after pulmonary metastasectomy. A univariate
      analyses revealed that the CEA level (p = 0.043) and the number of pulmonary
      metastases (p = 0.047) were prognostic factors for survival. The CEA level was an
      independent prognostic factor in a multivariate analysis (relative risk = 2.01, p
      = 0.037). Among cases with elevated preoperative CEA levels, those whose CEA
      level normalized after metastasectomy had a better prognosis compared with those
      whose CEA level decreased but was still high, or whose level increased after
      metastasectomy (median survival time of 41.8 months compared with 28.1 or 15.7
      months, respectively p = 0.021). CONCLUSION: The CEA level can be a predictive
      marker for the prognosis in patients with pulmonary metastases from colorectal
      carcinoma.

PMID- 26289632
TI  - Spermiotoxicity of commercial condoms made from polyurethane, polyisoprene and
      latex, using domestic ruminants as an experimental animal model.
AB  - The use of condoms could provide a means of collecting high-quality spermatozoa
      from different species under physiological ejaculation conditions. However,
      certain condom materials may affect sperm functionality. This study examined the
      spermiotoxicity of different commercial condom materials towards ram and goat
      spermatozoa. Sperm samples were diluted in Tyrode's medium and placed in contact
      with a piece of condom material (polyurethane, polyisoprene or latex) and
      incubated for 30 or 90 min. Contact time in the polyisoprene and latex treatments
      affected some sperm variables; no such effects were seen, however, in the
      polyurethane treatments. For ram spermatozoa in contact with polyisoprene, the
      percentage of dead spermatozoa with a damaged acrosome increased at 90 min, while
      for spermatozoa in contact with latex, the percentage of live spermatozoa with an
      intact acrosome decreased. For goat spermatozoa in contact with both polyisoprene
      and latex, the percentage of dead spermatozoa with a damaged acrosome increased
      at 90 min, while for spermatozoa in contact with polyisoprene, the percentage of
      live spermatozoa with an intact acrosome decreased. In conclusion, latex and
      polyisoprene contain components that affect sperm motility, plasma membrane
      integrity and acrosome function. Polyurethane does not seem to reduce the quality
      of semen.

PMID- 26289633
TI  - Combined selective dorsal rhizotomy and scoliosis correction procedure in
      patients with cerebral palsy.
AB  - Intrathecal baclofen (ITB) therapy for spasticity has been suggested to
      accelerate the development of scoliosis. We present the case of a 17-year-old
      female patient with cerebral palsy who had ITB therapy from the age of 11 years.
      During this period, she developed a severe scoliosis measuring 86 degrees  from
      T11 to L4, with pain due to costo-pelvic impingement. Her baclofen pump had
      reached its end of life and required replacement if ITB therapy was to continue.
      This coincided with plans for scoliosis corrective surgery. METHODS: We performed
      scoliosis correction along with removal of baclofen pump and selective dorsal
      rhizotomy (SDR), as a single combined procedure. SDR was performed instead of ITB
      pump replacement for management of spasticity. RESULTS: Following surgery,
      scoliosis improved to 24 degrees . At 6 month follow-up, there was significant
      improvement in spasticity and quality of life. CONCLUSIONS: This report
      illustrates the feasibility of a combined procedure to correct scoliosis and
      manage spasticity with SDR. We present the case details, our management and
      review of the published literature regarding the factors influencing treatment of
      scoliosis and spasticity.

PMID- 26289634
TI  - Is pelvic incidence a constant, as everyone knows? Changes of pelvic incidence in
      surgically corrected adult sagittal deformity.
AB  - PURPOSE: Previous investigations have recognized the critical role of pelvic
      parameters in the setting of a fixed sagittal deformity. Pelvic incidence (PI) is
      a constant, as everyone knows. However, PI might change reciprocally because of
      increased shear force on the sacroiliac joint, following surgical correction of
      fixed lumbar lordosis (LL). The disparity in PI after surgery according to the
      surgical method, and its impact on final follow-up, has not been reported. This
      study was undertaken to analyze the disparity of PI before and after surgery, and
      to evaluate its impact on final sagittal alignment in surgically corrected
      lordosis when there is immediate postoperative normal alignment following
      correction of adult sagittal deformity. METHODS: A prospective study of 29
      subjects with adult spinal deformity (average age: 67.9 years) was conducted. At
      final evaluation after a minimum 2-year follow-up, normal sagittal alignment was
      achieved following consecutive sagittal correction. Surgical changes were
      measured by serial, pelvic standing, lateral, and whole spine radiographs,
      spinopelvic parameters measured included PI, sacral slope (SS), pelvic tilt (PT),
      LL, thoracic kyphosis (TK), and sagittal alignment. RESULTS: The mean LL was 0.2
      degrees  before surgery; -59.3 degrees  after surgery with pedicle subtraction
      osteotomy (PSO) (n = 20), anterior lumbar interbody fusion (ALIF) (n = 20, 33
      segments), and posterior lumbar interbody fusion (PLIF) (n = 21, 36 segments);
      and -57.5 degrees  at last follow-up. The sagittal vertical axis was +14.8 cm
      before surgery, -0.7 cm after surgery, and 2.2 cm at last follow-up. The mean PI
      was 49.4 degrees  before surgery, and increased to 55.2 degrees  after surgery,
      57.5 degrees  at 1-year follow-up, and 58.8 degrees  at last follow-up (P =
      0.02). The mean disparity in PI preoperatively and at last follow-up was 11.4
      degrees  without sacropelvic fixation (n = 18), and 5.9 degrees  with sacropelvic
      fixation (n = 11) (P = 0.002). Analysis revealed the disparity of PI to be
      significantly greater in non-sacropelvic fixation, and correlated with the follow
      up period (R = 0.442, P = 0.016), but not with age, bone mineral density (BMD),
      number of fused segments, correction methods, corrected LL, or sagittal
      alignment. CONCLUSIONS: PI increased in all patients with surgically corrected,
      adult sagittal deformity, following surgical correction of fixed LL. The
      disparity of PI after surgery was significantly higher in non-sacropelvic
      fixation, and showed a significant correlation with follow-up period without
      influence on sagittal alignment at last follow-up.

PMID- 26289635
TI  - Nanog RNA-binding proteins YBX1 and ILF3 affect pluripotency of embryonic stem
      cells.
AB  - Nanog is a well-known transcription factor that plays a fundamental role in stem
      cell self-renewal and the maintenance of their pluripotent cell identity. There
      remains a large data gap with respect to the spectrum of the key pluripotency
      transcription factors' interaction partners. Limited information is available
      concerning Nanog-associated RNA-binding proteins (RBPs), and the intrinsic
      protein-RNA interactions characteristic of the regulatory activities of Nanog.
      Herein, we used an improved affinity protocol to purify Nanog-interacting RBPs
      from mouse embryonic stem cells (ESCs), and 49 RBPs of Nanog were identified.
      Among them, the interaction of YBX1 and ILF3 with Nanog mRNA was further
      confirmed by in vitro assays, such as Western blot, RNA immunoprecipitation
      (RIP), and ex vivo methods, such as immunofluorescence staining and fluorescent
      in situ hybridization (FISH), MS2 in vivo biotin-tagged RNA affinity purification
      (MS2-BioTRAP). Interestingly, RNAi studies revealed that YBX1 and ILF3 positively
      affected the expression of Nanog and other pluripotency-related genes.
      Particularly, downregulation of YBX1 or ILF3 resulted in high expression of
      mesoderm markers. Thus, a reduction in the expression of YBX1 and ILF3 controls
      the expression of pluripotency-related genes in ESCs, suggesting their roles in
      further regulation of the pluripotent state of ESCs. 

PMID- 26289636
TI  - Follicular psoriasis: an under-recognized condition.

PMID- 26289637
TI  - Fuzziness endows viral motif-mimicry.
AB  - Motif-mimicry is exploited by viruses to interfere with host regulatory networks
      and has also been suggested as a prevalent strategy for eukaryotic and
      prokaryotic pathogens. Using the same peptide motif however does not guarantee
      more effective interactions with the host. Motif-mediated interactions require a
      flexible or disordered environment, with structural and dynamic features that
      should differ between the competing host and viral proteins. Using the eukaryotic
      linear motif (ELM) database we analyzed the protein regions which contained the
      eukaryotic and viral motifs, including human and human virus ELMs with common
      target sites. We found that although the eukaryotic motifs are associated with a
      lack of structure, they are more stable than their flanking regions and can serve
      as molecular recognition elements. In contrast, eukaryotic viral motifs are often
      located in more ordered regions, but have increased local flexibility or disorder
      compared to their embedding environment. Most viral ELMs are devoid of stable
      binding elements and remain fuzzy after binding. Fuzziness reduces the entropic
      cost of binding and imparts versatile interaction modes to increase binding
      promiscuity and to compete with multiple host peptides. Fuzzy interactions confer
      further functional benefits such as the combinatorial usage of motifs, and a fine
      tuning affinity via post-translational modifications. 

PMID- 26289638
TI  - Retraction of '"Clickable", Trifunctional Magnetite Nanoparticles and Their
      Chemoselective Biofunctionalization'.

PMID- 26289639
TI  - Oral iron supplements increase hepcidin and decrease iron absorption from daily
      or twice-daily doses in iron-depleted young women.
AB  - Iron supplements acutely increase hepcidin, but the duration and magnitude of the
      increase, its dose dependence, and its effects on subsequent iron absorption have
      not been characterized in humans. Better understanding of these phenomena might
      improve oral iron dosing schedules. We investigated whether the acute iron
      induced increase in hepcidin influences iron absorption of successive daily iron
      doses and twice-daily iron doses. We recruited 54 nonanemic young women with
      plasma ferritin <=20 ug/L and conducted: (1) a dose-finding investigation with 40
      , 60-, 80-, 160-, and 240-mg labeled Fe as [(57)Fe]-, [(58)Fe]-, or [(54)Fe]
      FeSO4 given at 8:00 am fasting on 1 or on 2 consecutive days (study 1, n = 25;
      study 2, n = 16); and (2) a study giving three 60-mg Fe doses (twice-daily
      dosing) within 24 hours (study 3, n = 13). In studies 1 and 2, 24 hours after
      doses >=60 mg, serum hepcidin was increased (P < .01) and fractional iron
      absorption was decreased by 35% to 45% (P < .01). With increasing dose,
      fractional absorption decreased (P < .001), whereas absolute absorption increased
      (P < .001). A sixfold increase in iron dose (40-240 mg) resulted in only a
      threefold increase in iron absorbed (6.7-18.1 mg). In study 3, total iron
      absorbed from 3 doses (2 mornings and an afternoon) was not significantly greater
      than that from 2 morning doses. Providing lower dosages (40-80 mg Fe) and
      avoiding twice-daily dosing maximize fractional absorption. The duration of the
      hepcidin response supports alternate day supplementation, but longer-term effects
      of these schedules require further investigation. These clinical trials were
      registered at www.ClinicalTrials.gov as #NCT01785407 and #NCT02050932. 

PMID- 26289641
TI  - Multicenter study of combination DEP regimen as a salvage therapy for adult
      refractory hemophagocytic lymphohistiocytosis.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a refractory immune disorder with a
      significant risk of death. Although standard therapy has dramatically improved
      survival in HLH patients, approximately 30%, especially adults, show no response
      to current treatment strategies. This prospective study aimed to investigate the
      efficacy of liposomal doxorubicin treatment combined with etoposide and
      methylprednisolone (doxorubicin-etoposide-methylprednisolone; DEP) as a salvage
      therapy for adult refractory HLH. Adult patients who did not achieve at least
      partial response 2 weeks after initial standard HLH therapy were enrolled in this
      study between June 2013 and June 2014. Response to salvage therapy was assessed
      at 2 and 4 weeks after initiation of DEP therapy and patients were followed until
      death or until November 2014. Sixty-three refractory HLH patients were enrolled,
      including 29 cases of lymphoma-associated HLH, 22 cases of Epstein-Barr virus
      associated HLH, and 4 cases of familial HLH. There were 8 cases with unknown
      underlying diseases. Seventeen cases (27.0%) achieved complete response and 31
      cases (49.2%) achieved partial response. The overall response was 76.2% (48/63).
      Patients who showed no response to DEP died within 4 weeks after salvage therapy.
      Twenty-nine of the 48 patients who achieved partial or complete response survived
      to subsequent chemotherapy, allogenic hematopoietic stem cell transplantation, or
      splenectomy. Our study suggests that DEP regimen is an effective salvage regimen
      for adult refractory HLH, which can prolong patient survival as we continue to
      understand the responsible mechanisms and bridge the gap between HLH and its
      underlying diseases. This study was registered in the Chinese Clinical Trials
      Registry Platform (http://www.chictr.org.cn/) as ChiCTR-IPC-14005514. 

PMID- 26289643
TI  - [Epithetic replacement in otorhinolaryngology].
AB  - The past century saw rapid development of craniofacial prostheses. Particularly
      the challenging issue of surgical fixation was the subject of intensive research
      and development. During the past three decades, the principle of osseointegration
      has proven to provide a reliable method for epithesis fixation. The continuous
      technical development of implant systems has led to almost minimally invasive
      surgical techniques, with ever increasing stability of the implants.
      Osseointegrated implants are a proven and durable solution in the rehabilitation
      of the patient with a defect in the craniofacial region. Overall complication
      rates are low. The design and mechanics of the implants, as well as the
      artificial body of the epithesis itself, are topics of current medical-technical
      research by anaplastologists and surgeons. Finally, functional prostheses, such
      as the tracheostomy epithesis, deserve particular attention. 

PMID- 26289644
TI  - [Health care policy 2013-2017: what is happening in this legislative period? An
      interview with Professor Dr. Edgar Franke, MdB (SPD)].

PMID- 26289640
TI  - Omenn syndrome associated with a functional reversion due to a somatic second
      site mutation in CARD11 deficiency.
AB  - Omenn syndrome (OS) is a severe immunodeficiency associated with erythroderma,
      lymphoproliferation, elevated IgE, and hyperactive oligoclonal T cells. A
      restricted T-cell repertoire caused by defective thymic T-cell development and
      selection, lymphopenia with homeostatic proliferation, and lack of regulatory T
      cells are considered key factors in OS pathogenesis. We report 2 siblings
      presenting with cytomegalovirus (CMV) and Pneumocystis jirovecii infections and
      recurrent sepsis; one developed all clinical features of OS. Both carried
      homozygous germline mutations in CARD11 (p.Cys150*), impairing NF-kappaB
      signaling and IL-2 production. A somatic second-site mutation reverting the stop
      codon to a missense mutation (p.Cys150Leu) was detected in tissue-infiltrating T
      cells of the OS patient. Expression of p.Cys150Leu in CARD11-deficient T cells
      largely reconstituted NF-kappaB signaling. The reversion likely occurred in a
      prethymic T-cell precursor, leading to a chimeric T-cell repertoire. We speculate
      that in our patient the functional advantage of the revertant T cells in the
      context of persistent CMV infection, combined with lack of regulatory T cells,
      may have been sufficient to favor OS. This first observation of OS in a patient
      with a T-cell activation defect suggests that severely defective T-cell
      development or homeostatic proliferation in a lymphopenic environment are not
      required for this severe immunopathology. 

PMID- 26289645
TI  - Editorial: Ageing in place, older people and community nursing: gerontological
      nursing in place.

PMID- 26289642
TI  - The forkhead transcription factor FOXP1 represses human plasma cell
      differentiation.
AB  - Expression of the forkhead transcription factor FOXP1 is essential for early B
      cell development, whereas downregulation of FOXP1 at the germinal center (GC)
      stage is required for GC B-cell function. Aberrantly high FOXP1 expression is
      frequently observed in diffuse large B-cell lymphoma and mucosa-associated
      lymphoid tissue lymphoma, being associated with poor prognosis. Here, by gene
      expression analysis upon ectopic overexpression of FOXP1 in primary human memory
      B cells (MBCs) and B-cell lines, combined with chromatin immunoprecipitation and
      sequencing, we established that FOXP1 directly represses expression of PRDM1,
      IRF4, and XBP1, transcriptional master regulators of plasma cell (PC)
      differentiation. In accordance, FOXP1 is prominently expressed in primary human
      naive and MBCs, but expression strongly decreases during PC differentiation.
      Moreover, as compared with immunoglobulin (Ig) M(+) MBCs, IgG(+) MBCs combine
      lower expression of FOXP1 with an enhanced intrinsic PC differentiation
      propensity, and constitutive (over)expression of FOXP1 in B-cell lines and
      primary human MBCs represses their ability to differentiate into PCs. Taken
      together, our data indicate that proper control of FOXP1 expression plays a
      critical role in PC differentiation, whereas aberrant expression of FOXP1 might
      contribute to lymphomagenesis by blocking this terminal B-cell differentiation. 

PMID- 26289646
TI  - Mutagenicity profile of atmospheric particulate matter in a small urban center
      subjected to airborne emission from vehicle traffic and sugar cane burning.
AB  - Atmospheric particulate matter (PM) is genotoxic and recently was classified as
      carcinogenic to humans by the International Agency for Research on Cancer. PM
      chemical composition varies depending on source and atmospheric conditions. The
      Salmonella/microsome assay is the most used mutagenicity test and can identify
      the major chemical classes responsible for observed mutagenicity. The objective
      of this work was to characterize the mutagenicity of PM samples from a
      countryside city, Limeira, Brazil, which is influenced by heavy traffic and sugar
      cane biomass burning. Six samples of total PM were collected. Air mass backward
      trajectories were calculated. Organic extracts were assayed using the
      Salmonella/microsome microsuspension mutagenicity assay using TA98, YG1041, and
      TA1538, with and without metabolic activation (S9). YG1041 was the most sensitive
      strain and mutagenicity reached 9,700 revertants per m(3) without metabolic
      activation. Potency for TA1538 was higher than TA98, indicating that this strain
      should be considered in air mutagenicity studies. The increased response to
      YG1041 relative to TA98, and the decreased response with S9, suggests that
      nitroaromatics are the major contributors. Limeira is among the most mutagenic
      cities in the world. High mutagenicity in Limeira seems to occur when the air
      mass from the area of sugarcane production is mixed with air from the region
      impacted by anthropogenic activities such as traffic. An increase in the
      formation of nitro-polycyclic aromatic hydrocarbons may result from longer
      contact time between the aromatic compounds and the atmosphere with high NOx and
      ozone concentration, although more studies are required to confirm this
      hypothesis.

PMID- 26289648
TI  - An approach for detecting five typical vegetation types on the Chinese Loess
      Plateau using Landsat TM data.
AB  - Remote sensing can provide large-scale spatial data for the detection of
      vegetation types. In this study, two shortwave infrared spectral bands (TM5 and
      TM7) and one visible spectral band (TM3) of Landsat 5 TM data were used to detect
      five typical vegetation types (communities dominated by Bothriochloa ischaemum,
      Artemisia gmelinii, Hippophae rhamnoides, Robinia pseudoacacia, and Quercus
      liaotungensis) using 270 field survey data in the Yanhe watershed on the Loess
      Plateau. The relationships between 200 field data points and their corresponding
      radiance reflectance were analyzed, and the equation termed the vegetation type
      index (VTI) was generated. The VTI values of five vegetation types were
      calculated, and the accuracy was tested using the remaining 70 field data points.
      The applicability of VTI was also tested by the distribution of vegetation type
      of two small watersheds in the Yanhe watershed and field sample data collected
      from other regions (Ziwuling Region, Huangling County, and Luochuan County) on
      the Loess Plateau. The results showed that the VTI can effectively detect the
      five vegetation types with an average accuracy exceeding 80 % and a
      representativeness above 85 %. As a new approach for monitoring vegetation types
      using remote sensing at a larger regional scale, VTI can play an important role
      in the assessment of vegetation restoration and in the investigation of the
      spatial distribution and community diversity of vegetation on the Loess Plateau.

PMID- 26289647
TI  - Multidisciplinary approach and anesthetic management of a surgical cancer patient
      with methylene tetrahydrofolate reductase deficiency: a case report and review of
      the literature.
AB  - INTRODUCTION: Hyperhomocysteinemia is a known risk factor for myocardial
      infarction, stroke, peripheral vascular disease, and thrombosis. Elevated plasma
      homocysteine levels have been demonstrated in patients with recurrent episodes or
      a single episode of thrombosis. Here we describe the development of
      cardiovascular disease as a complication of a surgical intervention in a patient
      with colorectal cancer and hyperhomocysteinemia. CASE PRESENTATION: A 65-year-old
      Caucasian man complained of pain and constipation, attributed to previously
      diagnosed adenocarcinoma (stage IIB) of the hepatic flexure. An anamnestic
      investigation showed that he had undergone two surgical interventions. During
      both, he suffered thrombotic postoperative complications, a deep vein thrombosis
      of the upper extremity after the first operation and retinal vein occlusion after
      the second. He was diagnosed with hyperhomocysteinemia associated with a
      homozygous C677T mutation of the gene encoding the enzyme
      methylenetetrahydrofolate reductase. Our patient was initially treated with folic
      acid and high-dose B vitamins. On day 7 he underwent a right hemicolectomy.
      Anesthesia was performed with sevoflurane in 40% O2 and without the use of
      nitrous oxide. Postoperatively, our patient remained on folic acid and B vitamins
      and was without immediate or subsequent complications. CONCLUSIONS: Neoplastic
      disease and related surgery followed by the administration of chemotherapeutic
      drugs alter the hemostatic balance in cancer patients. Those suspected of also
      having a thrombophilic disease require a thorough laboratory diagnostic workup,
      including a molecular analysis aimed at identifying the genetic mutation
      responsible for the hyperhomocysteinemia, as indicated. The case described in
      this report highlights the importance of a multidisciplinary approach that
      includes expertise in peri-operative anesthesia, surgery, oncology, and
      hematology.

PMID- 26289649
TI  - Morpho-orthographic segmentation without semantics.
AB  - Masked priming studies have repeatedly provided evidence for a form-based morpho
      orthographic segmentation mechanism that blindly decomposes any word with the
      mere appearance of morphological complexity (e.g., corn + er). This account has
      been called into question by Baayen et al. Psychological Review, 118, 438-482
      (2011), who pointed out that the prime words previously tested in the morpho
      orthographic condition vary in the extent to which the suffix conveys regular
      meaning. In the present study, we investigated whether evidence for morpho
      orthographic segmentation can be obtained with a set of tightly controlled prime
      words that are entirely semantically opaque. Using a visual lexical decision
      task, we compared priming from truly suffixed primes (hunter-HUNT), completely
      opaque pseudo-suffixed primes (corner-CORN), and non-suffixed primes (cashew
      CASH). The results show comparable magnitudes of priming for the truly suffixed
      and pseudo-suffixed primes, and no priming from non-suffixed primes, and
      therefore provide further important evidence in support of morpho-orthographic
      segmentation processes operating in the absence of any possible role for
      semantics.

PMID- 26289650
TI  - Erratum to: Grammatical constraints on phonological encoding in speech
      production.

PMID- 26289651
TI  - Reversal of Opioid-Induced Ventilatory Depression Using Low-Dose Naloxone (0.04
      mg): a Case Series.
AB  - INTRODUCTION: Naloxone is commonly administered in emergency department (ED) to
      reverse opioid intoxication. Several naloxone dose recommendations exist for
      acute management of opioid intoxication based on limited published clinical data.
      A case series of ED patients with opioid-induced ventilatory depression that was
      reversed using a low-dose naloxone (0.04 mg with titration) is presented.
      METHODS: ED patients with opioid-induced ventilatory depression requiring
      naloxone administration were identified through medical toxicology consultation.
      Retrospective review of medical records was performed. Collected data included
      history, and pre- and post-naloxone data, including respiratory rate (RR), pulse
      oximetry (pulse ox), end-tidal CO2 level (ET-CO2), and Richmond Agitation
      Sedation Scale (RASS). RESULTS: Fifteen ED patients with moderate to severe
      opioid-induced ventilatory depression (median RR, 6 breaths/min) who were managed
      using low-dose naloxone strategy were identified. Twelve of 15 patients reported
      ingestion of methadone (range, 30 to 180 mg). The median naloxone dose of 0.08 mg
      (range, 0.04 to 0.12 mg) reversed opioid-induced ventilatory and CNS depression.
      Two patients experienced acute opioid withdrawal after receiving 0.08 mg.
      CONCLUSION: ED patients with moderate to severe opioid-induced ventilatory
      depression can be reversed using 0.04 mg IV naloxone with appropriate dose
      titration.

PMID- 26289652
TI  - Butane Hash Oil Burns Associated with Marijuana Liberalization in Colorado.
AB  - Butane hash oil (BHO), also known as "amber," "dab," "glass," "honey," "shatter,"
      or "wax," is a potent marijuana concentrate, containing up to 90 %
      tetrahydrocannabinol (THC). BHO is easily manufactured using highly volatile
      butane as a solvent. Our objective was to characterize hydrocarbon burns
      associated with BHO manufacture in Colorado. This was a cross-sectional study
      utilizing the National Burn Repository to capture all hydrocarbon burns reported
      to the local burn center from January 1st, 2008, through August 31st, 2014. We
      abstracted demographic and clinical variables from medical records for patients
      admitted for hydrocarbon burns associated with butane hash oil extraction. Twenty
      nine cases of BHO burns were admitted to the local burn center during the study
      period. Zero cases presented prior to medical liberalization, 19 (61.3 %) during
      medical liberalization (Oct 2009-Dec 2013), and 12 (38.7 %) in 2014 since
      legalization. The majority of cases were Caucasian (72.4 %) males (89.7 %).
      Median age was 26 (range 15-58). The median total-body-surface-area (TBSA) burn
      size was 10 % (TBSA range 1-90 %). Median length of hospital admission was 10
      days. Six required intubation for airway protection (21 %). Nineteen required
      skin grafting, eight wound care only, one required surgical fracture repair, and
      one required surgical debridement. Hydrocarbon burns associated with hash oil
      production have increased since the liberalization of marijuana policy in
      Colorado. A combination of public health messaging, standardization of
      manufacturing processes, and worker safety regulations are needed to decrease the
      risks associated with BHO production.

PMID- 26289653
TI  - Lettuce contact allergy.
AB  - Lettuce (Lactuca sativa L.) and its varieties are important vegetable crops
      worldwide. They are also well-known, rarely reported, causes of contact allergy.
      As lettuce allergens and extracts are not commercially available, the allergy may
      be underdiagnosed. The aims of this article are to present new data on lettuce
      contact allergy and review the literature. Lettuce is weakly allergenic, and
      occupational cases are mainly reported. Using aimed patch testing in Compositae
      allergic patients, two recent Danish studies showed prevalence rates of positive
      lettuce reactions of 11% and 22%. The majority of cases are non-occupational, and
      may partly be caused by cross-reactivity. The sesquiterpene lactone mix seems to
      be a poor screening agent for lettuce contact allergy, as the prevalence of
      positive reactions is significantly higher in non-occupationally sensitized
      patients. Because of the easy degradability of lettuce allergens, it is
      recommended to patch test with freshly cut lettuce stem and supplement this with
      Compositae mix. As contact urticaria and protein contact dermatitis may present
      as dermatitis, it is important to perform prick-to-prick tests, and possibly
      scratch patch tests as well. Any person who is occupationally exposed to lettuce
      for longer periods, especially atopics, amateur gardeners, and persons keeping
      lettuce-eating pets, is potentially at risk of developing lettuce contact
      allergy. 

PMID- 26289654
TI  - Arachnid aloft: directed aerial descent in neotropical canopy spiders.
AB  - The behaviour of directed aerial descent has been described for numerous taxa of
      wingless hexapods as they fall from the tropical rainforest canopy, but is not
      known in other terrestrial arthropods. Here, we describe similar controlled
      aerial behaviours for large arboreal spiders in the genus Selenops (Selenopidae).
      We dropped 59 such spiders from either canopy platforms or tree crowns in Panama
      and Peru; the majority (93%) directed their aerial trajectories towards and then
      landed upon nearby tree trunks. Following initial dorsoventral righting when
      necessary, falling spiders oriented themselves and then translated head-first
      towards targets; directional changes were correlated with bilaterally asymmetric
      motions of the anterolaterally extended forelegs. Aerial performance (i.e. the
      glide index) decreased with increasing body mass and wing loading, but not with
      projected surface area of the spider. Along with the occurrence of directed
      aerial descent in ants, jumping bristletails, and other wingless hexapods, this
      discovery of targeted gliding in selenopid spiders further indicates strong
      selective pressures against uncontrolled falls into the understory for arboreal
      taxa. 

PMID- 26289655
TI  - An integrated approach to quantitative modelling in angiogenesis research.
AB  - Angiogenesis, the process by which new vessels form from existing ones, plays an
      important role in many developmental processes and pathological conditions. We
      study angiogenesis in the context of a highly controllable experimental
      environment: the cornea micropocket assay. Using a multidisciplinary approach
      that combines experiments, image processing and analysis, and mathematical
      modelling, we aim to provide mechanistic insight into the action of two
      angiogenic factors, vascular endothelial growth factor A (VEGF-A) and basic
      fibroblast growth factor (bFGF). We use image analysis techniques to extract
      quantitative data, which are both spatially and temporally resolved, from
      experimental images, and we develop a mathematical model, in which the corneal
      vasculature evolves in response to both VEGF-A and bFGF. The experimental data
      are used for model parametrization, while the mathematical model is used to
      assess the utility of the cornea micropocket assay and to characterize proposed
      synergies between VEGF-A and bFGF.

PMID- 26289656
TI  - The control of sea lice in Atlantic salmon by selective breeding.
AB  - Sea lice threaten the welfare of farmed Atlantic salmon and the sustainability of
      fish farming across the world. Chemical treatments are the major method of
      control but drug resistance means that alternatives are urgently needed.
      Selective breeding can be a cheap and effective alternative. Here, we combine
      experimental trials and diagnostics to provide a practical protocol for
      quantifying resistance to sea lice. We then combined quantitative genetics with
      epidemiological modelling to make the first prediction of the response to
      selection, quantified in terms of reduced need for chemical treatments. We
      infected over 1400 young fish with Lepeophtheirus salmonis, the most important
      species in the Northern Hemisphere. Mechanisms of resistance were expressed early
      in infection. Consequently, the number of lice per fish and the ranking of
      families were very similar at 7 and 17 days post infection, providing a stable
      window for assessing susceptibility to infection. The heritability of lice
      numbers within this time window was moderately high at 0.3, confirming that
      selective breeding is viable. We combined an epidemiological model of sea lice
      infection and control on a salmon farm with genetic variation in susceptibility
      among individuals. We simulated 10 generations of selective breeding and examined
      the frequency of treatments needed to control infection. Our model predicted that
      substantially fewer chemical treatments are needed to control lice outbreaks in
      selected populations and chemical treatment could be unnecessary after 10
      generations of selection. Selective breeding for sea lice resistance should
      reduce the impact of sea lice on fish health and thus substantially improve the
      sustainability of Atlantic salmon production. 

PMID- 26289658
TI  - Adaptation mechanism of interlimb coordination in human split-belt treadmill
      walking through learning of foot contact timing: a robotics study.
AB  - Human walking behaviour adaptation strategies have previously been examined using
      split-belt treadmills, which have two parallel independently controlled belts. In
      such human split-belt treadmill walking, two types of adaptations have been
      identified: early and late. Early-type adaptations appear as rapid changes in
      interlimb and intralimb coordination activities when the belt speeds of the
      treadmill change between tied (same speed for both belts) and split-belt
      (different speeds for each belt) configurations. By contrast, late-type
      adaptations occur after the early-type adaptations as a gradual change and only
      involve interlimb coordination. Furthermore, interlimb coordination shows after
      effects that are related to these adaptations. It has been suggested that these
      adaptations are governed primarily by the spinal cord and cerebellum, but the
      underlying mechanism remains unclear. Because various physiological findings
      suggest that foot contact timing is crucial to adaptive locomotion, this paper
      reports on the development of a two-layered control model for walking composed of
      spinal and cerebellar models, and on its use as the focus of our control model.
      The spinal model generates rhythmic motor commands using an oscillator network
      based on a central pattern generator and modulates the commands formulated in
      immediate response to foot contact, while the cerebellar model modifies motor
      commands through learning based on error information related to differences
      between the predicted and actual foot contact timings of each leg. We
      investigated adaptive behaviour and its mechanism by split-belt treadmill walking
      experiments using both computer simulations and an experimental bipedal robot.
      Our results showed that the robot exhibited rapid changes in interlimb and
      intralimb coordination that were similar to the early-type adaptations observed
      in humans. In addition, despite the lack of direct interlimb coordination
      control, gradual changes and after-effects in the interlimb coordination appeared
      in a manner that was similar to the late-type adaptations and after-effects
      observed in humans. The adaptation results of the robot were then evaluated in
      comparison with human split-belt treadmill walking, and the adaptation mechanism
      was clarified from a dynamic viewpoint. 

PMID- 26289659
TI  - Mapping high-growth phenotypes in the flux space of microbial metabolism.
AB  - Experimental and empirical observations on cell metabolism cannot be understood
      as a whole without their integration into a consistent systematic framework.
      However, the characterization of metabolic flux phenotypes is typically reduced
      to the study of a single optimal state, such as maximum biomass yield that is by
      far the most common assumption. Here, we confront optimal growth solutions to the
      whole set of feasible flux phenotypes (FFPs), which provides a benchmark to
      assess the likelihood of optimal and high-growth states and their agreement with
      experimental results. In addition, FFP maps are able to uncover metabolic
      behaviours, such as aerobic fermentation accompanying exponential growth on
      sugars at nutrient excess conditions, that are unreachable using standard models
      based on optimality principles. The information content of the full FFP space
      provides us with a map to explore and evaluate metabolic behaviour and
      capabilities, and so it opens new avenues for biotechnological and biomedical
      applications. 

PMID- 26289660
TI  - Piriformis Syndrome in a Young Child--An Unusual Clinical Entity.

PMID- 26289661
TI  - Children Like Chocolates; Does Chocolates Like Children or Their Hearts?

PMID- 26289657
TI  - Heparan sulfate and heparin interactions with proteins.
AB  - Heparan sulfate (HS) polysaccharides are ubiquitous components of the cell
      surface and extracellular matrix of all multicellular animals, whereas heparin is
      present within mast cells and can be viewed as a more sulfated, tissue-specific,
      HS variant. HS and heparin regulate biological processes through interactions
      with a large repertoire of proteins. Owing to these interactions and diverse
      effects observed during in vitro, ex vivo and in vivo experiments, manifold
      biological/pharmacological activities have been attributed to them. The
      properties that have been thought to bestow protein binding and biological
      activity upon HS and heparin vary from high levels of sequence specificity to a
      dependence on charge. In contrast to these opposing opinions, we will argue that
      the evidence supports both a level of redundancy and a degree of selectivity in
      the structure-activity relationship. The relationship between this apparent
      redundancy, the multi-dentate nature of heparin and HS polysaccharide chains,
      their involvement in protein networks and the multiple binding sites on proteins,
      each possessing different properties, will also be considered. Finally, the role
      of cations in modulating HS/heparin activity will be reviewed and some of the
      implications for structure-activity relationships and regulation will be
      discussed. 

PMID- 26289662
TI  - Proton Migration in Clusters Consisting of Protonated Pyridine Solvated by Water
      Molecules.
AB  - Proton transfer (PT) from protonated pyridine to water molecules is observed
      after excitation of microhydrated protonated pyridine (Py) clusters PyH(+) (H2
      O)n (n=0-5) is induced by a single collision with an Ar atom at high incident
      velocity (95*10(3)  m s(-1) ). Besides the fragmentation channel associated with
      the evaporation of water molecules, the charged-fragment mass spectrum shows
      competition between the production of the PyH(+) ion (or its corresponding
      charged fragments) and the production of H(+) (H2 O) or H(+) (H2 O)2 ions. The
      increase in the production of protonated water fragments as a function of the
      number of H2 O molecules in the parent cluster ion as well sd the observation of
      a stable H(+) (H2 O)2 fragment, even in the case of the dissociation of PyH(+)
      (H2 O)2 , are evidence of the crucial role of PT in the relaxation process, even
      for a small number of solvating water molecules. 

PMID- 26289663
TI  - The discovery of novel antifungal scaffolds by structural simplification of the
      natural product sampangine.
AB  - Natural products are important sources of therapeutic drugs. However, it is a
      challenge to simplify the structure of natural products without decreasing the
      biological activity. Here we provide the first example of the successful
      simplification of an antifungal natural product. Starting from sampangine, two
      novel simplified scaffolds with excellent antifungal activity were discovered. 

PMID- 26289664
TI  - Interleukin-4 polymorphism is associated with severity of respiratory syncytial
      virus infection.
AB  - AIM: Respiratory syncytial virus (RSV) infection is a major health problem in
      young children. This study aimed to investigate whether the interleukin (IL)-4 
      590C/T and -33 C/T polymorphisms were associated with the susceptibility to RSV
      infection in Chinese Han children and with the severity of the infection.
      METHODS: The IL-4 -590C/T and -33 C/T SNPs were evaluated in 218 inpatients with
      RSV bronchiolitis and 303 healthy controls. The severity of RSV bronchiolitis was
      evaluated using a respiratory scoring system. RESULTS: The frequencies of IL-4 
      590 CC, CT and TT in the 218 RSV bronchiolitis patients versus the 303 controls
      were 1.4% versus 1.7%, 21.1% versus 34% and 77.5% versus 64.4%, respectively. The
      frequencies of IL-4 -33 CC, CT and TT were 1.4%, 20.6% and 78%, respectively, in
      RSV bronchiolitis patients and 2.3%, 35.6% and 62%, respectively, in the
      controls. The frequencies of the IL-4 -590C/T and -33 C/T polymorphisms were
      significantly different between the two groups. There was a significant
      difference in the frequency of the T-T haplotype formed by -590C/T and -33C/T
      between the two groups. The respiratory score of the RSV bronchiolitis cases with
      -590TT was 3.02 +/- 0.44, which was significantly higher than those with -590CT
      (2.80 +/- 0.44). The score for patients with -33TT was 3.03 +/- 0.43, which was
      significantly higher than the score of 2.78 +/- 0.46 for patients with -33CT.
      CONCLUSIONS: In Chinese Han children, the IL-4 -590C/T and -33 C/T polymorphisms
      were associated with the susceptibility to RSV and the severity of the infection.

PMID- 26289665
TI  - Coexpression of human perforin improves yeast-mediated delivery of DNA and mRNA
      to mammalian antigen-presenting cells.
AB  - Previous studies underlined the capacity of recombinant yeast as efficient
      vehicle for the targeted delivery of functional nucleic acids as well as
      proteinaceous antigens to mammalian antigen-presenting cells (APCs). To improve
      this yeast-mediated cargo transport into APCs, we investigated the impact of
      coexpression of the human membrane-perturbing protein perforin in comparison with
      bacterial listeriolysin O (LLO) on the yeast-based delivery of DNA, mRNA and
      proteins to mammalian APCs. In contrast to LLO, a cholesterol-dependent pore
      forming toxin of Listeria, intracellular expression of human perforin in
      Saccharomyces cerevisiae had no impact on yeast cell viability, while its
      coexpression significantly increased translocation of ovalbumin and subsequent
      activation of ovalbumin-specific T lymphocytes. Likewise, perforin improved the
      expression of the model antigen enhanced green fluorescent protein after yeast
      mediated DNA and mRNA delivery, whereas LLO was only able to enhance DNA
      delivery. Taken together, our data show that human perforin, besides bacterial
      hemolysins, represents a promising means to improve the yeast-mediated delivery
      of functional nucleic acids and proteins to mammalian APCs. 

PMID- 26289666
TI  - CRISPR/Cas9 DNA cleavage at SNP-derived PAM enables both in vitro and in vivo
      KRT12 mutation-specific targeting.
AB  - CRISPR/Cas9-based therapeutics hold the possibility for permanent treatment of
      genetic disease. The potency and specificity of this system has been used to
      target dominantly inherited conditions caused by heterozygous missense mutations
      through inclusion of the mutated base in the short-guide RNA (sgRNA) sequence.
      This research evaluates a novel approach for targeting heterozygous single
      nucleotide polymorphisms (SNPs) using CRISPR/Cas9. We determined that a mutation
      within KRT12, which causes Meesmann's epithelial corneal dystrophy (MECD), leads
      to the occurrence of a novel protospacer adjacent motif (PAM). We designed an
      sgRNA complementary to the sequence adjacent to this SNP-derived PAM and
      evaluated its potency and allele specificity both in vitro and in vivo. This
      sgRNA was found to be highly effective at reducing the expression of mutant KRT12
      mRNA and protein in vitro. To assess its activity in vivo we injected a combined
      Cas9/sgRNA expression construct into the corneal stroma of a humanized MECD mouse
      model. Sequence analysis of corneal genomic DNA revealed non-homologous end
      joining repair resulting in frame-shifting deletions within the mutant KRT12
      allele. This study is the first to demonstrate in vivo gene editing of a
      heterozygous disease-causing SNP that results in a novel PAM, further
      highlighting the potential for CRISPR/Cas9-based therapeutics. 

PMID- 26289667
TI  - Exploring evidence of positive selection reveals genetic basis of meat quality
      traits in Berkshire pigs through whole genome sequencing.
AB  - BACKGROUND: Natural and artificial selection following domestication has led to
      the existence of more than a hundred pig breeds, as well as incredible variation
      in phenotypic traits. Berkshire pigs are regarded as having superior meat quality
      compared to other breeds. As the meat production industry seeks selective
      breeding approaches to improve profitable traits such as meat quality,
      information about genetic determinants of these traits is in high demand.
      However, most of the studies have been performed using trained sensory panel
      analysis without investigating the underlying genetic factors. Here we
      investigate the relationship between genomic composition and this phenotypic
      trait by scanning for signatures of positive selection in whole-genome sequencing
      data. RESULTS: We generated genomes of 10 Berkshire pigs at a total of 100.6
      coverage depth, using the Illumina Hiseq2000 platform. Along with the genomes of
      11 Landrace and 13 Yorkshire pigs, we identified genomic variants of 18.9 million
      SNVs and 3.4 million Indels in the mapped regions. We identified several
      associated genes related to lipid metabolism, intramuscular fatty acid
      deposition, and muscle fiber type which attribute to pork quality (TG, FABP1,
      AKIRIN2, GLP2R, TGFBR3, JPH3, ICAM2, and ERN1) by applying between population
      statistical tests (XP-EHH and XP-CLR). A statistical enrichment test was also
      conducted to detect breed specific genetic variation. In addition, de novo short
      sequence read assembly strategy identified several candidate genes (SLC25A14,
      IGF1, PI4KA, CACNA1A) as also contributing to lipid metabolism. CONCLUSIONS:
      Results revealed several candidate genes involved in Berkshire meat quality; most
      of these genes are involved in lipid metabolism and intramuscular fat deposition.
      These results can provide a basis for future research on the genomic
      characteristics of Berkshire pigs.

PMID- 26289668
TI  - Do unfavourable working conditions explain mental health inequalities between
      ethnic groups? Cross-sectional data of the HELIUS study.
AB  - BACKGROUND: Ethnic inequalities in mental health have been found in many high
      income countries. The purpose of this study is to test whether mental health
      inequalities between ethnic groups are mediated by exposure to unfavourable
      working conditions. METHODS: Workers (n = 6278) were selected from baseline data
      of the multi-ethnic HELIUS study. Measures included two indices of unfavourable
      working conditions (lack of recovery opportunities, and perceived work stress),
      and two mental health outcomes (generic mental health: MCS-12 and depressive
      symptoms: PHQ-9). Mediation of the relationships between ethnicity and mental
      health by unfavourable working conditions was tested using the bias-corrected
      bootstrap confidence intervals technique. Linear models with and without the
      mediators included, and adjusted for gender and age. Attenuation was calculated
      as the change in B between the models with and without mediators. RESULTS: The
      sample comprised Dutch (1355), African Surinamese (1290), South-Asian Surinamese
      (1121), Turkish (1090), Ghanaian (729), and Moroccan (693) workers. After
      controlling for age and gender, all ethnic minorities had a higher risk of mental
      health problems as compared to the Dutch host population, with the exception of
      Ghanaians in the case of depressive symptoms, and African Surinamese workers with
      regard to both outcomes. The Turkish group stands out with the lowest mental
      health on both mental health indices, followed by Moroccan and South-Asian
      Surinamese workers. A lack of recovery opportunities mediated the relationship
      between ethnic group and a higher risk of mental health problems. Perceived work
      stress did not contribute to the explanation of ethnic inequalities. CONCLUSIONS:
      The higher risk of mental health problems in ethnic minority groups can be partly
      accounted for by a lack of recovery opportunities at work, but not by perceived
      work stress. This may imply that workplace prevention targeting recovery
      opportunities have the potential to reduce ethnic inequalities, but ethnic
      specific experiences at the workplace need to be further explored.

PMID- 26289669
TI  - Erratum to: A comprehensive grid to evaluate case management's expected
      effectiveness for community-dwelling frail older people: results from a multiple,
      embedded case study.

PMID- 26289670
TI  - Vagotomy attenuates bleomycin-induced pulmonary fibrosis in mice.
AB  - The progression of pulmonary fibrosis (PF) entails a complex network of
      interactions between multiple classes of molecules and cells, which are closely
      related to the vagus nerve. Stimulation of the vagus nerve increases fibrogenic
      cytokines in humans, therefore, activation of the nerve may promote PF. The
      hypothesis was tested by comparing the extent and severity of fibrosis in lungs
      with and without vagal innervation in unilaterally vagotomized mice. The results
      show that in vagotomized lungs, there were less collagen staining, less severe
      fibrotic foci (subpleural, peri-vascular and peri-bronchiolar lesions) and
      destruction of alveolar architecture; decreased collagen deposition (denervated
      vs intact: COL1alpha1, 19.1 +/- 2.2 vs 22.0 +/- 2.6 ng/mg protein; COL1alpha2,
      4.5 +/- 0.3 vs 5.7 +/- 0.5 ng/mg protein; p < 0.01, n = 21) and protein levels of
      transforming growth factor beta and interleukin 4; and fewer myofibroblast
      infiltration (denervated vs intact: 1.2 +/- 0.2 vs 3.2 +/- 0.6 cells/visual
      field; p < 0.05, n = 6) and M2 macrophages [though the infiltration of
      macrophages was increased (denervated vs intact: 112 +/- 8 vs 76 +/- 9
      cells/visual field; p < 0.01, n = 6), the percentage of M2 macrophages was
      decreased (denervated vs intact: 31 +/- 4 vs 57 +/- 9%; p < 0.05, n = 5)]. It
      indicated that the vagus nerve may influence PF by enhancing fibrogenic factors
      and fibrogenic cells. 

PMID- 26289672
TI  - Recent developments in novel drug delivery systems for wound healing.
AB  - INTRODUCTION: Complete regeneration and restoration of the skin's structure and
      function with no or minimal scarring remains the goal of wound healing research.
      Novel pharmaceutical carriers have the potential to deliver wound healing drugs
      such as antibiotics, antimicrobials, human EGFs, and so on. Thus, offering a
      potential platform to overcome the limitations of conventional wound dressings.
      AREAS COVERED: This review will describe various techniques such as microspheres,
      nanoparticles, liposomes, solid lipid nanoparticles, nano and microemulsions,
      sponges and wafers, and so on, that are successfully applied as carriers for
      wound healing drugs. Results of various studies including in vitro and in vivo
      experiments are also discussed. EXPERT OPINION: Controlled and localized delivery
      of wound healing drugs to the wounds is more convenient than systemic
      administration as higher concentrations of the medication are delivered directly
      to the desired area in a sustained manner. They are also capable of providing
      optimum environmental conditions to facilitate wound healing while eliminating
      the need for frequent changes of dressings. As the number of people suffering
      from chronic wounds is increasing around the world, controlled delivery of wound
      healing agents have enormous potential for patient-friendly wound management.

PMID- 26289671
TI  - The structure of an endogenous Drosophila centromere reveals the prevalence of
      tandemly repeated sequences able to form i-motifs.
AB  - Centromeres are the chromosomal loci at which spindle microtubules attach to
      mediate chromosome segregation during mitosis and meiosis. In most eukaryotes,
      centromeres are made up of highly repetitive DNA sequences (satellite DNA)
      interspersed with middle repetitive DNA sequences (transposable elements).
      Despite the efforts to establish complete genomic sequences of eukaryotic
      organisms, the so-called 'finished' genomes are not actually complete because the
      centromeres have not been assembled due to the intrinsic difficulties in
      constructing both physical maps and complete sequence assemblies of long
      stretches of tandemly repetitive DNA. Here we show the first molecular structure
      of an endogenous Drosophila centromere and the ability of the C-rich dodeca
      satellite strand to form dimeric i-motifs. The finding of i-motif structures in
      simple and complex centromeric satellite DNAs leads us to suggest that these
      centromeric sequences may have been selected not by their primary sequence but by
      their ability to form noncanonical secondary structures. 

PMID- 26289673
TI  - Applications of nanoparticles in cancer medicine and beyond: optical and
      multimodal in vivo imaging, tissue targeting and drug delivery.
AB  - INTRODUCTION: Nanotechnology has opened up the way to the engineering of new
      organized materials endowed with improved performances. In the past decade,
      engineered nanoparticles (NPs) have been progressively implemented by exploiting
      synthetic strategies that yield complex materials capable of performing functions
      with applications also in medicine. Indeed, in the field of 'nanomedicine' it has
      been explored the possibility to design multifunctional nanosystems,
      characterized by high analytical performances and stability, low toxicity and
      specificity towards a given cell target. AREA COVERED: In this review article, we
      summarize the advances in the engineering of NPs for biomedical applications,
      from optical imaging (OI) to multimodal OI and targeted drug delivery. For this
      purpose, we will provide some examples of how investigations in nanomedicine can
      support preclinical and clinical research generating innovative diagnostic and
      therapeutic strategies in oncology. EXPERT OPINION: The progressive breakthroughs
      in nanomedicine have supported the development of multifunctional and multimodal
      NPs. In particular, NPs are significantly impacting the diagnostic and
      therapeutic strategies since they allow the development of: NP-based OI probes
      containing more than one modality-specific contrast agent; surface functionalized
      NPs for specific 'molecular recognition'. Therefore, the design and
      characterization of innovative NP-based systems/devices have great applicative
      potential into the medical field.

PMID- 26289674
TI  - Functionalised particles using dry powder coating in pharmaceutical drug
      delivery: promises and challenges.
AB  - INTRODUCTION: Production of functionalised particles using dry powder coating is
      a one-step, environmentally friendly process that paves the way for the
      development of particles with targeted properties and diverse functionalities.
      AREAS COVERED: Applying the first principles in physical science for powders,
      fine guest particles can be homogeneously dispersed over the surface of larger
      host particles to develop functionalised particles. Multiple functionalities can
      be modified including: flowability, dispersibility, fluidisation, homogeneity,
      content uniformity and dissolution profile. The current publication seeks to
      understand the fundamental underpinning principles and science governing dry
      coating process, evaluate key technologies developed to produce functionalised
      particles along with outlining their advantages, limitations and applications and
      discusses in detail the resultant functionalities and their applications. EXPERT
      OPINION: Dry particle coating is a promising solvent-free manufacturing
      technology to produce particles with targeted functionalities. Progress within
      this area requires the development of continuous processing devices that can
      overcome challenges encountered with current technologies such as heat generation
      and particle attrition. Growth within this field requires extensive research to
      further understand the impact of process design and material properties on
      resultant functionalities.

PMID- 26289675
TI  - Inhaled antibiotics in the treatment of non-cystic fibrosis bronchiectasis:
      clinical and drug delivery perspectives.
AB  - INTRODUCTION: Non-cystic fibrosis bronchiectasis (NCFB) is a chronic,
      progressive, suppurative lung disease characterized by permanent dilatation of
      bronchial subdivisions, which further causes accumulation of sputum and bacterial
      infections. The advent of inhaled antibiotics over the past two decades has been
      expected to effectively attenuate the problem of chronic bacterial infections in
      CF and NCFB subjects with higher, local drug concentrations and minimal systemic
      side effects. AREAS COVERED: This review summarizes and evaluates current
      clinical evidence of efficacy and adverse effects of inhaled antibiotics in NCFB,
      as well as ongoing preclinical and clinical studies, followed by a discussion of
      issues and challenges in clinical practice and drug delivery strategies, together
      with future research directions. EXPERT OPINION: The evidence base of the
      clinical efficacy of inhaled antibiotics in NCFB is limited and the degrees of
      reported clinical benefits have been modest and conflicting. Challenges
      surrounding inhaled antibiotics application and development include the lack of
      knowledge of disease factors and optimum management strategies, unreceptive lung
      pathophysiology and the lack of factors that support compliance and tolerability.
      Nonetheless, research continues to give birth to new clinical findings and novel
      formulations such as combination antibiotics and sustained-release formulations,
      which add great value to the development of efficacious, safe and convenient
      inhalable antibiotics of the future.

PMID- 26289676
TI  - Intranasal gene delivery for treating Parkinson's disease: overcoming the blood
      brain barrier.
AB  - INTRODUCTION: Developing a disease-modifying gene therapy for Parkinson's disease
      (PD) has been a high priority for over a decade. However, due to the inability of
      large biomolecules to cross the blood-brain barrier (BBB), the only means of
      delivery to the brain has been intracerebral infusion. Intranasal administration
      offers a non-surgical means of bypassing the BBB to deliver neurotrophic factors,
      and the genes encoding them, directly to the brain. AREAS COVERED: This review
      summarizes: i) evidence demonstrating intranasal delivery to the brain of a
      number of biomolecules having therapeutic potential for various CNS disorders;
      and ii) evidence demonstrating neuroprotective efficacy of a subset of
      biomolecules specifically for PD. The intersection of these two spheres
      represents the area of opportunity for development of new intranasal gene
      therapies for PD. To that end, our laboratory showed that intranasal
      administration of glial cell line-derived neurotrophic factor (GDNF), or plasmid
      DNA nanoparticles encoding GDNF, provides neuroprotection in a rat model of PD,
      and that the cells transfected by the nanoparticle vector are likely to be
      pericytes. EXPERT OPINION: A number of genes encoding neurotrophic factors have
      therapeutic potential for PD, but few have been tested by the intranasal route
      and shown to be neuroprotective in a model of PD. Intranasal delivery provides a
      largely unexplored, promising approach for development of a non-invasive gene
      therapy for PD.

PMID- 26289678
TI  - Tumor hypoxia induces nuclear paraspeckle formation through HIF-2alpha dependent
      transcriptional activation of NEAT1 leading to cancer cell survival.
AB  - Correction to: Oncogene (2015) 34, 4482-4490; doi:10.1038/onc.2014.378; published
      online 24 November 2014. Following the online publication of this article, the
      authors have noticed a misspelt surname: S Hider should read S Haider. There is
      also an addition to the acknowledgements to read 'This study makes use of data
      generated by the Molecular Taxonomy of Breast Cancer International Consortium,
      which was funded by Cancer Research UK and the British Columbia Cancer Agency
      Branch'. The corrected article appears in this issue. The authors would like to
      apologise for any inconvenience this may cause.

PMID- 26289679
TI  - Evaluation of T-wave alternans activity under stress conditions after 5 d and 21
      d of sedentary head-down bed rest.
AB  - It is well known that prolonged microgravity leads to cardiovascular
      deconditioning, inducing significant changes in autonomic control of the
      cardiovascular system. This may adversely influence cardiac repolarization, and
      provoke cardiac rhythm disturbances. T-wave alternans (TWA), reflecting temporal
      and spatial repolarization heterogeneity, could be affected. The aim of this work
      was to test the hypothesis that 5 d and 21 d head-down (-6 degrees ) bed rest
      (HDBR) increases TWA, thus suggesting a higher underlying electrical instability
      and related arrhythmogenic risk. Forty-four healthy male volunteers were enrolled
      in the experiments as part of the European Space Agency's HDBR studies. High
      fidelity ECG was recorded during orthostatic tolerance (OT) and aerobic power
      (AP) tests, before (PRE) and after HDBR (POST). A multilead scheme for TWA
      amplitude estimation was used, where non-normalized and T-wave amplitude
      normalized TWA indices were computed. In addition, spectral analysis of heart
      rate variability during OT was assessed. Both 5 d and 21 d HDBR induced a
      reduction in orthostatic tolerance time (OTT), as well as a decrease in maximal
      oxygen uptake and reserve capacity, thus suggesting cardiovascular
      deconditioning. However, TWA indices were found not to increase. Interestingly,
      subjects with lower OTT after 5 d HDBR also showed higher TWA during recovery
      after OT testing, associated with unbalanced sympathovagal response, even before
      the HDBR. In contrast with previous observations, augmented ventricular
      heterogeneity related to 5 d and 21 d HDBR was not sufficient to increase TWA
      under stress conditions.

PMID- 26289677
TI  - Predicting potential ranges of primary malaria vectors and malaria in northern
      South America based on projected changes in climate, land cover and human
      population.
AB  - BACKGROUND: Changes in land use and land cover (LULC) as well as climate are
      likely to affect the geographic distribution of malaria vectors and parasites in
      the coming decades. At present, malaria transmission is concentrated mainly in
      the Amazon basin where extensive agriculture, mining, and logging activities have
      resulted in changes to local and regional hydrology, massive loss of forest
      cover, and increased contact between malaria vectors and hosts. METHODS:
      Employing presence-only records, bioclimatic, topographic, hydrologic, LULC and
      human population data, we modeled the distribution of malaria and two of its
      dominant vectors, Anopheles darlingi, and Anopheles nuneztovari s.l. in northern
      South America using the species distribution modeling platform Maxent. RESULTS:
      Results from our land change modeling indicate that about 70,000 km(2) of forest
      land would be lost by 2050 and 78,000 km(2) by 2070 compared to 2010. The Maxent
      model predicted zones of relatively high habitat suitability for malaria and the
      vectors mainly within the Amazon and along coastlines. While areas with malaria
      are expected to decrease in line with current downward trends, both vectors are
      predicted to experience range expansions in the future. Elevation, annual
      precipitation and temperature were influential in all models both current and
      future. Human population mostly affected An. darlingi distribution while LULC
      changes influenced An. nuneztovari s.l. distribution. CONCLUSION: As the region
      tackles the challenge of malaria elimination, investigations such as this could
      be useful for planning and management purposes and aid in predicting and
      addressing potential impediments to elimination.

PMID- 26289680
TI  - Characterization of acidic and basic variants of IgG1 therapeutic monoclonal
      antibodies based on non-denaturing IEF fractionation.
AB  - Characterization of both the acidic and basic regions of imaged capillary
      isoelectric focusing (icIEF) profile of an IgG1 antibody was achieved through
      preparative immobilized pH gradient isoelectric focusing (IPG-IEF) fractionation.
      Recent attempts at using this method to fractionate charge variants of monoclonal
      antibodies (mAbs) have shown promising results, but identification of the
      chemical modifications in the variants was limited to the basic species. We have
      optimized the method to achieve enrichment of each variant across the icIEF
      profile of an IgG1 mAb. The fractionation was followed by extended
      characterization to elucidate the composition of the acidic, main, and basic
      species observed in the icIEF profile. Deamidation, sialylation, glycation, and
      fragmentation were identified as the main modifications contributing to acidic
      variants of the mAb while C-terminal lysine, C-terminal proline amidation, and
      uncyclized N-terminal glutamine were the major species contributing to the basic
      variants. This characterization allows a better understanding of the
      modifications that contribute to the charge variants observed by icIEF,
      facilitating the evaluation of impacts on product safety and efficacy.

PMID- 26289682
TI  - Effect of Active Music Therapy and Individualized Listening to Music on Dementia:
      A Multicenter Randomized Controlled Trial.
AB  - OBJECTIVES: To assess the effects of active music therapy (MT) and individualized
      listening to music (LtM) on behavioral and psychological symptoms of dementia
      (BPSDs) in persons with dementia (PWDs). DESIGN: Randomized controlled trial.
      SETTING: Nine Italian institutions. PARTICIPANTS: Persons with moderate to severe
      dementia and BPSDs (N = 120) were randomized to one of three treatments.
      INTERVENTIONS: All groups received standard care (SC), and two groups attended 20
      individualized MT or LtM sessions, twice a week, in addition to SC. MEASUREMENTS:
      The Neuropsychiatric Inventory (NPI), Cornell Scale for Depression in Dementia
      (CSDD), and Cornell-Brown Scale for Quality of Life in Dementia (CBS-QoL) were
      administered before treatment, after treatment, and at follow-up to evaluate
      behavioral and psychological outcomes. A specific coding scheme (Music Therapy
      Check List-Dementia) was used to evaluate the MT process. RESULTS: Behavioral
      assessment did not show significant differences between groups. All groups showed
      a reduction over time in NPI global score (P <= .001), CSDD (P = .001), and CBS
      QoL (P = .01). The NPI global score fell 28% in the MT group, 12% in the LtM
      group, and 21% in the SC group at the end of treatment. An exploratory post hoc
      analysis showed similar within-group improvements for the NPI Delusion, Anxiety,
      and Disinhibition subscales. In the MT group, communication and relationships
      between the music therapists and PWDs showed a positive albeit nonsignificant
      trend during treatment. CONCLUSION: The addition of MT or LtM to standard care
      did not have a significant effect on BPSDs in PWDs. Further studies on the
      effects of the integration of standard care with different types of music
      interventions on BPSD in PWD are warranted.

PMID- 26289681
TI  - Prescription Opioids and Risk of Dementia or Cognitive Decline: A Prospective
      Cohort Study.
AB  - OBJECTIVES: To determine whether prescription opioid use is associated with
      higher dementia risk or greater cognitive decline. DESIGN: Prospective cohort
      study. SETTING: Group Health, an integrated healthcare delivery system.
      PARTICIPANTS: Community-dwelling individuals aged 65 and older without dementia
      with at least 10 years of Group Health enrollment at baseline (N = 3,434; median
      age 74). MEASUREMENTS: The Cognitive Abilities Screening Instrument (CASI) was
      administered every 2 years. Low scores triggered detailed evaluation, and a
      multidisciplinary committee assigned dementia diagnoses. From computerized
      pharmacy data, cumulative opioid exposure was defined as total standardized doses
      (TSDs) dispensed over 10 years (excluding the most recent year because of
      possible prodromal symptoms). For comparison, use of nonsteroidal anti
      inflammatory drugs (NSAIDs), characterized similarly, was examined. Dementia risk
      was analyzed using Cox proportional hazards models and CASI trajectory using
      linear regression models and generalized estimating equations. RESULTS: Seven
      hundred ninety-seven participants (23%) developed dementia over a mean follow-up
      of 7.3 years; 637 (19%) had possible or probable Alzheimer's disease. For
      cumulative opioid use, the hazard ratios (HRs) for dementia were 1.06 (95%
      confidence interval (CI) = 0.88-1.26) for 11 to 30 TSDs, 0.88 (95% CI = 0.70
      1.09) for 31 to 90 TSDs, and 1.29 (95% CI = 1.02-1.62) for 91 or more TSDs,
      versus 0 to 10 TSDs. A similar pattern was seen for NSAID use. Heavier opioid use
      was not associated with more-rapid cognitive decline. CONCLUSION: People with the
      heaviest opioid or NSAID use had slightly higher dementia risk than people with
      little or no use. These results may reflect an effect of chronic pain on
      cognition or residual confounding. Although opioids have other risks, little
      evidence of long-term cognitive harm specific to opioids was found.

PMID- 26289684
TI  - Effect of Nurse-Implemented Transitional Care for Chinese Individuals with
      Chronic Heart Failure in Hong Kong: A Randomized Controlled Trial.
AB  - OBJECTIVES: To determine the effect of nurse-implemented transitional care (TC)
      on readmission and mortality rates in Chinese individuals with chronic heart
      failure (CHF) in Hong Kong. DESIGN: Single-center randomized controlled trial of
      TC versus usual care (UC). SETTING: University-affiliated hospital in Hong Kong.
      PARTICIPANTS: Hospitalized Chinese individuals with CHF (N = 178; aged 78.6 +/-
      6.9, 45% male). MEASUREMENTS: The TC group received a predischarge visit, two
      home visits, and then regular telephone calls over 9 months to provide self-care
      education and support, optimized health surveillance, and facilitation in use of
      community services. Primary endpoints were event-free survival, all-cause
      hospital readmission, and mortality during the 9-month follow-up. Secondary
      endpoints were length of hospital stay, self-care, and health-related quality of
      life (HRQL). Data were analyzed using survival analysis and generalized
      estimating equations, following an intention-to-treat principle. RESULTS:
      Survival analysis indicated no significant differences in event-free survival,
      hospital readmission, or mortality between the TC and UC groups, although the TC
      group had a lower hospital readmission rate at 6 weeks (8.1% vs 16.3%, P = .048)
      and lower mortality at 9 months (4.1% vs 13.8%, P = .03). The TC group also had a
      shorter hospital stay (P = .006) and significantly better self-care and HRQL.
      Because of attrition, sensitivity analyses were conducted to examine whether the
      intention-to-treat assumption affected the results. Per-protocol population
      analyses (hazard ratio (HR) = 0.40, 95% confidence interval (CI) = 0.17-0.93) and
      worst-case-scenario analysis (HR = 0.44, 95% CI = 0.25-0.77) suggested a lower
      mortality risk in the TC group. CONCLUSION: The translation of individual
      centered nurse-implemented TC to the Chinese culture and healthcare context of
      Hong Kong appears beneficial.

PMID- 26289683
TI  - Infectious Burden and Cognitive Decline in the Northern Manhattan Study.
AB  - OBJECTIVES: To determine whether infectious burden (IB) is associated with worse
      performance and decline on a battery of neuropsychological tests. DESIGN:
      Prospective cohort study (Northern Manhattan Study (NOMAS)). SETTING: Community.
      PARTICIPANTS: A subsample of 588 stroke-free NOMAS participants with IB and
      cognitive data (mean age 71 +/- 8, 62% female, 14% white, 16% black, 70%
      Hispanic) and 419 with repeat cognitive testing. MEASUREMENTS: Samples used for
      IB data were collected at baseline. Two waves of neurocognitive assessments
      occurred during follow-up. Participants underwent a neuropsychological battery
      and had repeated testing (mean time span 6 +/- 2 years). Using factor analysis
      derived domain-specific Z scores for language, memory, executive function, and
      processing speed, associations between a quantitative stroke risk-weighted IB
      index (IBI), based on five common infections (Chlamydia pneumoniae, Helicobacter
      pylori, cytomegalovirus, herpes simplex viruses 1 and 2), and cognitive
      performance and decline in each domain was examined. RESULTS: Adjusting for
      demographic characteristics, socioeconomic status, crystallized cognitive
      abilities, and vascular risk factors, the IBI was inversely associated with
      executive function at baseline (beta = -0.10, P = .01) but not with baseline
      language, memory, or processing speed performance in adjusted analyses. The IBI
      was associated with cognitive decline in the memory domain, adjusting for
      demographic and vascular risk factors (P = .02). CONCLUSION: A quantitative
      stroke risk-weighted measure of IB explained variability in baseline executive
      function performance and associated with decline in memory. Past exposure to
      common infections may contribute to vascular cognitive impairment and warrants
      further study.

PMID- 26289685
TI  - Abuse in Mexican Older Adults with Long-Term Disability: National Prevalence and
      Associated Factors.
AB  - OBJECTIVES: To determine the prevalence of self-reported abuse in elderly Mexican
      adults with long-term disabilities and to identify associated risk factors.
      DESIGN: Secondary analysis of the Perception of Disability in Mexican Population
      2010 survey. SETTING: Mexico. PARTICIPANTS: Individuals aged 60 and older with
      long-term disabilities without cognitive decline (N = 1,089). MEASUREMENTS: The
      elder abuse variable was constructed from the 21 questions included in the survey
      that assessed the presence of physical, psychological, sexual, and financial
      exploitation. Independent variables included demographic characteristics, self
      rated health, disability (number of functional domains or basic activities),
      multimorbidity, emotional symptoms, health resources used, and informal help.
      RESULTS: The prevalence of elder abuse was 32.1%. The most frequent type of abuse
      was psychological (28.1%). Nearly 58% of respondents reported one type of abuse,
      34% reported two types, and 8% reported more than three types. The most common
      combination of two types of abuse was psychological with financial exploitation.
      Variables associated with the presence of psychological, physical, and sexual
      abuse (conflict abuse) were age 80 and older, 9 or more years of education,
      unemployment, negative self-rated health, three or more disabilities, emotional
      symptoms, and history of hospitalization. Financial exploitation was associated
      with age 80 and older, being married or living with a partner, 9 or more years of
      education, unemployment, living in an urban area, negative self-rated health,
      three or more disabilities, emotional symptoms, and history of hospitalization.
      CONCLUSION: The prevalence of abuse in elderly Mexican adults with long-term
      disabilities is high. Associated factors were level of education, number of
      disabilities, and health status. Further studies should explore the applicability
      of these results to other populations.

PMID- 26289687
TI  - Statement of Principle.

PMID- 26289688
TI  - Edward.

PMID- 26289686
TI  - Body Mass Index Trajectories in Relation to Change in Lean Mass and Physical
      Function: The Health, Aging and Body Composition Study.
AB  - OBJECTIVES: To examine body mass index (BMI) trajectories with change in lean
      mass and physical function in old age. DESIGN: Prospective cohort study. SETTING:
      Health, Aging and Body Composition Study. PARTICIPANTS: Black and white men (n =
      482) and women (n = 516) aged 73.1 +/- 2.7 and initially free of disability.
      MEASUREMENTS: A group-based trajectory model was used to determine BMI
      trajectories, the path a person's BMI followed over 9 years. Lean mass, gait
      speed, grip strength, and knee extension strength were assessed at baseline and
      after 9 years, and relative changes were calculated. Multivariable linear
      regression was used to determine associations between trajectories and relative
      change in lean mass and physical function. RESULTS: Four BMI trajectories were
      identified for men and four for women. Although all demonstrated a decline in
      BMI, the rate of decline differed according to trajectory for women only. Men in
      Trajectory 4 (mean BMI at baseline 33.9 +/- 2.3 kg/m(2) ) declined more than
      those in Trajectory 1 (mean BMI at baseline 22.9 +/- 1.6 kg/m(2) ) in gait speed
      (-9.91%, 95% confidence interval (CI) = -15.15% to -4.67%) and leg strength (
      8.63%, 95% CI = -15.62% to -1.64%). Women in Trajectory 4 (mean BMI at baseline
      34.9 +/- 3.0 kg/m(2) ) had greater losses than those in Trajectory 1 (mean BMI at
      baseline 20.5 +/- 1.6 kg/m(2) ) in lean mass in the arms (-3.19%, 95% CI = -6.16%
      to -0.23%). No other associations were observed. CONCLUSION: Obese men had the
      highest risk of decline in physical function despite similar weight loss between
      trajectories, whereas overweight and obese women who lost the most weight had the
      greatest risk of lean mass loss. The weight at which a person enters old age is
      informative for predicting loss in lean mass and physical function, illustrating
      the importance of monitoring weight.

PMID- 26289689
TI  - Over the Rainbow.

PMID- 26289690
TI  - Things Are Better Today.

PMID- 26289691
TI  - Delayed Pharyngeal Response in CHEW-SWALLOW Does Not Increase Risk of Aspiration
      in Individuals with Stroke.

PMID- 26289692
TI  - Hyponatremia and Fracture Risk: A Hospital-Based Case--Control Study.

PMID- 26289693
TI  - Poor Balance as a Noncognitive Predictor of Incident Dementia.

PMID- 26289694
TI  - Do Acetylcholinesterase Inhibitors Increase Anxiety and Depression in Elderly
      Adults with Dementia?

PMID- 26289695
TI  - Effect of Sodium Phosphate Enemas on Serum Calcium and Phosphate Concentrations
      in Older Adult Inpatients.

PMID- 26289696
TI  - Asymptomatic Floor-of-Mouth Mass in a 79-Year-Old Woman Misinterpreted As a
      Sublingual Gland Mucous Extravasation Cyst.

PMID- 26289697
TI  - Failure of Glucose Monitoring in an Individual with Pseudohypoglycemia.

PMID- 26289698
TI  - Hypocalcemic Cardiomyopathy Due to Vitamin D Deficiency in a Very Old Man.

PMID- 26289699
TI  - A Rare Case of Systemic Lupus Erythematosus in an Elderly Man.

PMID- 26289700
TI  - Neurosyphilis: An Uncommon Cause of Dementia.

PMID- 26289702
TI  - An Unsuspected Cause of Hyponatremia: Beer Potomania.

PMID- 26289703
TI  - Routine Colonoscopic Evaluation May Be Recommended in Elderly Adults Diagnosed
      with Non-Hodgkin Lymphoma.

PMID- 26289701
TI  - Atypical Presentation of Celiac Disease in an Elderly Adult: Celiac Crisis.

PMID- 26289704
TI  - Sixty-Eight-Year-Old Man Presenting with Concurrent Microscopic Polyangiitis and
      Prostate Cancer.

PMID- 26289706
TI  - A Challenging Decision to Anticoagulate in an Older Adult with Rheumatoid
      Arthritis.

PMID- 26289705
TI  - Reversible Cognitive Impairment Associated with the Use of Dabigatran.

PMID- 26289707
TI  - An Unusual Case of Hemiballism-Hemichorea Associated with Nonketotic
      Hyperglycemia in Association with a Centrum Semiovale Stroke.

PMID- 26289708
TI  - Guidelines for the Clinical Diagnosis of Diabetes Mellitus-Related Dementia.

PMID- 26289709
TI  - Be Mindful of the Caregiver.

PMID- 26289710
TI  - Analysis of Nursing Home Prescriptions for Atrial Fibrillation: Practitioners and
      Guidelines, Which Is Wrong?

PMID- 26289711
TI  - Functional Decline Not Seen in Hospital in the Home.

PMID- 26289712
TI  - Response to Corvol and Colleagues.

PMID- 26289715
TI  - A new bioactive steroidal ketone from the South China Sea sponge Xestospongia
      testudinaria.
AB  - A new steroidal ketone (1), with an ergosta-22,25-diene side chain, was obtained
      from the South China Sea marine sponge Xestospongia testudinaria. The structure
      of 1 was determined on the basis of detailed spectroscopic analysis and by
      comparison with literature. Compound 1 exhibited significant inhibitory activity
      against protein tyrosine phosphatase 1B (PTP1B), a key target for the treatment
      of type II diabetes and obesity, with an IC50 value of 4.27 +/- 0.55 MUM, which
      is comparable with the positive control oleanolic acid (IC50 = 2.63 +/- 0.22
      MUM). 

PMID- 26289716
TI  - Sex differences in brain MRI abnormalities and neurodevelopmental outcomes in a
      rat model of neonatal hypoxia-ischemia.
AB  - PURPOSE/AIM OF THE STUDY: Hypoxic-ischemic brain injury (HIBI) is associated with
      high mortality and neurodevelopmental deficits. We explored gender influence in a
      HIBI rat model. MATERIALS AND METHODS: Sprague-Dawley rats underwent HIBI on
      postnatal day (P) 7. Nervous reflexes, footprints, Morris water maze performances
      and magnetic resonance imaging (MRI) were analyzed. RESULTS: Mortality rate was
      higher in HIBI males (20%) than in females (12.5%). Growth rate was slower in the
      HIBI group (p < 0.05), but was similar between HIBI males and females. HIBI rats
      showed impaired performances in the cliff aversion reflex, negative geotaxis
      reflex and gait tests at P14 (p < 0.05), but not at P9 or P11. There were no
      significant differences for the cliff aversion reflex and gait tests between
      genders. Negative geotaxis reflex impairment at P14 was more severe in HIBI males
      (p < 0.05). Step length and toe distance contralateral (but not ipsilateral) to
      the cerebral damage were shorter in HIBI rats, and were shorter in HIBI males
      than females (p < 0.05). Morris water maze latency time and swimming distance
      were longer in the HI group than in controls, and prolonged in HIBI males
      compared with females (p < 0.05). In the HIBI group, MRI showed more severe
      injury at P10 and P67 in males than in females (p < 0.05). CONCLUSIONS: Male rats
      are more vulnerable to the detrimental consequences of HIBI, with more severe
      nervous reflex deficits, brain injury, memory impairment and hemiplegic paralysis
      than female rats. Serial neurobehavioral follow-up is still executed on the HIBI
      infants who is absent of detectable abnormalities in early children.

PMID- 26289717
TI  - Private schooling and admission to medicine: a case study using matched samples
      and causal mediation analysis.
AB  - BACKGROUND: Are applicants from private schools advantaged in gaining entry to
      degrees in medicine? This is of international significance and there is
      continuing research in a range of nations including the USA, the UK, other
      English-speaking nations and EU countries. Our purpose is to seek causal
      explanations using a quantitative approach. METHODS: We took as a case study
      admission to medicine in the UK and drew samples of those who attended private
      schools and those who did not, with sample members matched on background
      characteristics. Unlike other studies in the area, causal mediation analysis was
      applied to resolve private-school influence into direct and indirect effects. In
      so doing, we sought a benchmark, using data for 2004, against which the
      effectiveness of policies adopted over the past decade can be assessed. RESULTS:
      Private schooling improved admission likelihood. This did not occur indirectly
      via the effect of school type on academic performance; but arose directly from
      attending private schools. A sensitivity analysis suggests this finding is
      unlikely to be eliminated by the influence of an unobserved variable.
      CONCLUSIONS: Academic excellence is not a certain pathway into medicine at
      university; yet applying with good grades after attending private school is more
      certain. The results of our paper differ from those in an earlier observational
      study and find support in a later study. Consideration of sources of difference
      from the earlier observational study suggest the causal approach offers
      substantial benefits and the consequences in the causal study for gender,
      ethnicity, socio-economic classification and region of residence provide a
      benchmark for assessing policy in future research.

PMID- 26289718
TI  - Multiple antigen target approach using the Accuplex4 BioCD system to detect
      Borrelia burgdorferi antibodies in experimentally infected and vaccinated dogs.
AB  - The primary objective of our study was to optimize detection of serum antibodies
      to Borrelia burgdorferi using a new commercial automated fluorescence system
      (Accuplex4 BioCD system, Antech Diagnostics, Lake Success, New York). The system
      used multiple natural and artificial peptides-outer surface proteins (OspA, OspC,
      OspF), an outer membrane protein (P39), and a proprietary synthetic peptide
      (small Lyme peptide [SLP])-and the results were compared with a commercially
      available enzyme-linked immunosorbent assay that uses a proprietary peptide (C6).
      Sera from 4 groups were evaluated: dogs vaccinated with 1 of 3 commercially
      available vaccines (n = 18); dogs infested with adult Ixodes scapularis (black
      legged tick; n = 18); dogs previously vaccinated and then infested with I.
      scapularis (n = 18); and dogs with B. burgdorferi infection that were then
      vaccinated (n = 14). All of the vaccines evaluated induced OspA responses.
      However, antibodies against OspF or C6 were not induced in any of the vaccinated
      dogs. Additionally, the OspF antibodies had 100% sensitivity and specificity when
      compared to antibodies against C6 peptide. In B. burgdorferi-infected dogs,
      antibodies against OspC and SLP were detected in serum sooner than antibodies
      against the other targets. Low levels of antibodies against OspA developed in 6
      of 14 B. burgdorferi-infected, unvaccinated dogs and had the shortest duration
      compared to the other antibodies. Detection of antibody responses to multiple B.
      burgdorferi targets with this system can be used to help differentiate vaccinated
      dogs from exposed dogs as well as acute infection from chronic infection. 

PMID- 26289719
TI  - Bovine tuberculosis in an Asian small-clawed otter (Aonyx cinerea) in the
      Republic of Korea.
AB  - Bovine tuberculosis caused by Mycobacterium bovis has a wide range of hosts
      including cattle and humans, but its incidence in otters is very rare. Our report
      describes a case of bovine tuberculosis in an Asian small-clawed otter (Aonyx
      cinerea). A deceased female otter ~2-3 years of age that was raised in an
      aquarium was submitted to the Animal and Plant Quarantine Agency (Anyang,
      Republic of Korea) for autopsy in June 2013. Following gross pathological
      examination, many white nodules were observed in the lungs and mesentery. The
      nodules showed central necrosis infiltrated with lymphocytes and macrophages and
      surrounded by fibrous tissue. Acid-fast bacteria were detected in the necrotic
      foci, but no fungi were observed. Molecular analysis led to the detection of M.
      bovis, which is identified in otters in some European countries such as Spain and
      France. 

PMID- 26289720
TI  - Nanostructured cobalt hydroxide thin films as high performance pseudocapacitor
      electrodes by graphene oxide wrapping.
AB  - We synthesized binder-free Co(OH)2 nanocrystals on nickel electrodes by the
      ammonia transfer method in an aqueous solution and kinetically-controlled their
      thickness and height to enhance the capacitance through the facile diffusion of
      electrolytes in the nanocrystals. As thinner Co(OH)2 films were developed, the
      specific capacitance increased up to 1260 F g(-1) at a current density of 10 A g(
      1). A thin layer of graphene oxide (GO) was used to wrap the Co(OH)2 nanocrystals
      to create a pseudocapacitor with high specific capacitance and good cyclic
      stability. This synthetic strategy enabled us to maximize the electrochemical
      cell performance, reaching a specific capacitance of 2710 F g(-1) under 10 A g(
      1). The GO coating provides an effective method to increase adhesion on the
      nickel electrodes and to reduce the decomposition of Co(OH)2 during the charge
      discharge process under high pH conditions. The prepared GO/Co(OH)2 nanocomposite
      layers provided not only high electron mobility but also ionic conductivity,
      especially when operated at a high current density. 

PMID- 26289724
TI  - Nonomuraea flavida sp. nov., a novel species of soil actinomycete isolated from
      Aconitum napellus rhizosphere.
AB  - A novel actinomycete strain, YN-5-1T, isolated from the rhizosphere soil of a
      medicinal plant, Aconitum napellus, was characterized by a polyphasic approach to
      determine its taxonomic position. The strain showed highest 16S rRNA gene
      sequence similarities of 97.3, 97.2 and 97.1 % to Nonomuraea turkmeniaca DSM
      43926T, Nonomuraea ferruginea DSM 43553T and Nonomuraea candida DSM 45086T,
      respectively. A wide range of genotypic and phenotypic characteristics, as well
      as levels of DNA-DNA relatedness between strain YN-5-1T and N. turkmeniaca DSM
      43926T (57.46 %), N. ferruginea DSM 43553T (53.50 %) and N. candida DSM 45086T
      (48.80 %), distinguished the novel isolate from its closest phylogenetic
      neighbours. The morphological characteristics of strain YN-5-1T were typical of
      the genus Nonomuraea. Chemotaxonomic characteristics, such as diagnostic diamino
      acid of the peptidoglycan, whole-cell sugars, phospholipid type, major
      menaquinone and major fatty acids, further supported the assignment of strain YN
      5-1T to the genus Nonomuraea. The G+C content of the genomic DNA was 72.1 mol%.
      Based on the above data, strain YN-5-1T is considered to represent a novel
      species of the genus Nonomuraea, for which the name Nonomuraea flavida sp. nov.
      is proposed. The type strain is YN-5-1T ( = CCTCC AB 2012909T = KCTC 29143T).

PMID- 26289723
TI  - Effect of comprehensive cardiac telerehabilitation on one-year cardiovascular
      rehospitalization rate, medical costs and quality of life: A cost-effectiveness
      analysis.
AB  - BACKGROUND: Notwithstanding the cardiovascular disease epidemic, current
      budgetary constraints do not allow for budget expansion of conventional cardiac
      rehabilitation programmes. Consequently, there is an increasing need for cost
      effectiveness studies of alternative strategies such as telerehabilitation. The
      present study evaluated the cost-effectiveness of a comprehensive cardiac
      telerehabilitation programme. DESIGN AND METHODS: This multi-centre randomized
      controlled trial comprised 140 cardiac rehabilitation patients, randomized (1:1)
      to a 24-week telerehabilitation programme in addition to conventional cardiac
      rehabilitation (intervention group) or to conventional cardiac rehabilitation
      alone (control group). The incremental cost-effectiveness ratio was calculated
      based on intervention and health care costs (incremental cost), and the
      differential incremental quality adjusted life years (QALYs) gained. RESULTS: The
      total average cost per patient was significantly lower in the intervention group
      (?2156 +/- ?126) than in the control group (?2720 +/- ?276) (p = 0.01) with an
      overall incremental cost of ?-564.40. Dividing this incremental cost by the
      baseline adjusted differential incremental QALYs (0.026 QALYs) yielded an
      incremental cost-effectiveness ratio of ?-21,707/QALY. The number of days lost
      due to cardiovascular rehospitalizations in the intervention group (0.33 +/-
      0.15) was significantly lower than in the control group (0.79 +/- 0.20) (p =
      0.037). CONCLUSIONS: This paper shows the addition of cardiac telerehabilitation
      to conventional centre-based cardiac rehabilitation to be more effective and
      efficient than centre-based cardiac rehabilitation alone. These results are
      useful for policy makers charged with deciding how limited health care resources
      should best be allocated in the era of exploding need.

PMID- 26289722
TI  - Increase of Unsaturated Fatty Acids (Low Melting Point) of Broiler Fatty Waste
      Obtained Through Staphylococcus xylosus Fermentation.
AB  - The increasing rise in the production of meat around the world causes a
      significant generation of agro-industrial waste--most of it with a low value
      added. Fatty wastes have the potential of being converted into biodiesel, given
      the overcome of technological and economical barriers, as well as its
      presentation in solid form. Therefore, the aim of this work was to investigate
      the capacity of Staphylococcus xylosus strains to modify the chemical structure
      of chicken fatty wastes intending to reduce the melting points of the wastes to
      mild temperatures, thereby breaking new ground in the production of biodiesel
      from these sources in an economically attractive and sustainable manner. The
      effects in time of fermentation and concentration of the fat in the medium were
      investigated, assessing the melting point and profile of fatty acids. The melting
      temperature showed a decrease of approximately 22  degrees C in the best
      operational conditions, due to reduction in the content of saturated fatty acids
      (high melting point) and increase of unsaturated fatty acids (low melting point).

PMID- 26289725
TI  - Central islands: rate and effect on visual recovery after phototherapeutic
      keratectomy.
AB  - PURPOSE: To retrospectively assess the proportion of patients affected by a
      central island (CI) and its effect on visual recovery after phototherapeutic
      keratectomy (PTK). METHODS: This retrospective study evaluated 30 eyes of 21
      consecutive patients (mean age +/- standard deviation, 69.6 +/- 6.8 years)
      undergoing PTK for the treatment of band keratopathy or granular corneal
      dystrophy. We investigated the rate of CI formation, which was defined as a
      steepening area of 3 D, 1.5 mm in diameter, on each corneal videokeratograph
      (ATLAS 9000; Carl Zeiss Meditec), and its effect on visual recovery at 3 months
      and at 1 year postoperatively. RESULTS: A CI was found in 22 of 30 eyes (73%) 3
      months postoperatively and in 14 of 25 eyes (56%) 1 year postoperatively. The
      degree of CI was significantly correlated with the change in logMAR corrected
      visual acuity (Spearman correlation coefficient r = 0.445, P = 0.026). The degree
      of CI in eyes with band keratopathy was significantly larger than that in eyes
      with granular dystrophy 1 year postoperatively (Mann-Whitney test, P = 0.045).
      The degree of CI was not significantly correlated with the ablation depth
      (Spearman correlation coefficient r = 0.116, P = 0.582) or the residual corneal
      thickness (r = -0.235, P = 0.278). CONCLUSIONS: CI formation was found in as many
      as 73 and 56% of patients 3 months and 1 year after PTK, respectively, using the
      VISX Star S4 excimer laser system, and significantly affected the improvement of
      visual acuity. The anti-CI program should be applied by the manufacturer, not
      only for corneal refractive surgery but also for PTK in a clinical setting.

PMID- 26289721
TI  - Lack of associations between betatrophin/ANGPTL8 level and C-peptide in type 2
      diabetic subjects.
AB  - BACKGROUND: Betatrophin has been suggested as an inducer of beta-cell
      proliferation in mice in addition to its function in regulating triglyceride.
      Recent data showed that betatrophin was increased in Type 2 Diabetes (T2D),
      however, its ability to induce insulin production has been questioned. We
      hypothesized that the increased betatrophin in T2D is not affecting insulin
      production from beta-cells. To test this hypothesis, we investigated the
      association between betatrophin and C-peptide level in humans, which acts as a
      measure of endogenous insulin production from beta-cells. METHODS: This study was
      designed to examine the association between plasma betatrophin level and C
      peptide in 749 T2D and non-diabetics. RESULTS: Betatrophin and C-peptide levels
      were higher in T2D subjects compared with non-diabetics subjects. Betatrophin
      showed strong correlation with C-peptide in non-diabetics subjects (r = 0.28, p =
      < 0.0001). No association between betatrophin and C-peptide were observed in T2D
      subjects (r = 0.07, p = 0.3366). Dividing obese and non-obese subjects into
      tertiles according to betatrophin level showed significantly higher C-peptide
      levels at higher tertiles of betatrophin in obese non-diabetics subjects P-trend
      = 0.0046. On the other hand, C-peptide level was significantly higher in subject
      with higher betatrophin level in non-diabetics subjects across all age groups but
      not in T2D subjects. Multiple logistic regression models adjusted for age, BMI,
      gender, ethnicity as well as C-peptide level showed that subjects in the highest
      tertiles of betatrophin had higher odds of having T2D [odd ratio (OR) = 7.3, 95%
      confidence interval (CI) 4.0-13.3]. CONCLUSION: Increased betatrophin level in
      obese subjects is correlated with an increase in C-peptide level; which is
      possibly caused by the increased insulin resistance. On the other hand, no
      correlation is observed between increased betatrophin level and C-peptide in T2D
      subjects. In conclusion, the increased betatrophin in T2D subject does not cause
      any increase in insulin production as indicated by C-peptide level.

PMID- 26289726
TI  - Coping profiles of young Athletes in their everyday life: A three-wave two-month
      study.
AB  - Young athletes in intensive training settings are confronted with a series of
      daily stressors although they have a smaller and less flexible coping repertoire
      than adults. Moreover, previous studies neglected the multivariate nature of
      coping. Therefore, the purpose of the current study was to first identify coping
      profiles of young athletes in response to daily stressors related to their
      competitive sport involvement. Second, the study examined: (a) if such profiles
      were similar across the three waves, (b) how many participants belonged to the
      same profile along the three waves, and (c) whether individuals from distinct
      profiles differed on burnout, stress, and recovery. One hundred and forty-seven
      young table-tennis players involved in intensive training settings completed the
      CICS, RESTQ-Sport, and ABQ three times during a 2-month period. Cluster analyses
      indicated three similar clusters across the three waves: task-oriented coping,
      distraction- and disengagement-oriented coping, and low coping profiles. The
      distribution of athletes significantly varied across waves. Burnout, stress, and
      recovery significantly differed across the coping profiles. Athletes from the
      task-oriented coping profile were characterized by the best psychological
      adjustment (high scores of recovery and low scores of stress and burnout). In
      contrast, athletes from the distraction- and disengagement-oriented coping
      profile were characterized by the worst psychological adjustment (high scores of
      stress and burnout and low scores of recovery). These findings highlighted that
      the coping profiles allow examining coping within a holistic approach, teasing
      out the complex associations with key outcomes, such as burnout, stress, and
      recovery.

PMID- 26289728
TI  - Italo-Swiss "Chalk and blackboard interactive 2-day workshop"-participants
      feedback.
AB  - Ten "chalk and blackboard interactive workshops" have taken place between 2011
      and 2015 in Southern Switzerland or Italy. Students, residents and expert
      pediatricians meet during 2 days and discuss 10-15 cases. Pediatricians promote
      reasoning, provide supporting information and correct statements. Emphasis is
      placed on history taking and examination, and on all participants being involved
      in a stimulating atmosphere. Thirty-seven participants were asked, >=3 months
      after workshop-completion, to evaluate the workshop and a recent teaching
      session. Thirty answered and scored the workshop as excellent (N = 24) or above
      average (N = 6). The scores assigned to the workshop were higher (P < 0.001) than
      those assigned to the lecture-based teaching.

PMID- 26289727
TI  - Furin-dependent CCL17-fused recombinant toxin controls HTLV-1 infection by
      targeting and eliminating infected CCR4-expressing cells in vitro and in vivo.
AB  - BACKGROUND: Adult T-cell leukemia (ATL) is caused by human T-cell leukemia virus
      type 1 (HTLV-1) infection. However, there are no therapies to prevent ATL
      development in high-risk asymptomatic carriers. To develop a therapy targeting
      HTLV-1-infected cells that are known to express CCR4 frequently, we tested
      whether truncated Pseudomonas exotoxin (PE38) fused to a CCR4 ligand,
      CCL17/thymus and activation-regulated chemokine (TARC), selectively eliminates
      such cells. RESULTS: Our data show that TARC-PE38 efficiently killed HTLV-1
      infected cell lines. It also shrank HTLV-1-associated solid tumors in an infected
      cell-engrafted mouse model. In HTLV-1-positive humanized mice, TARC-PE38 markedly
      inhibited the proliferation of HTLV-1-infected human CD4(+)CD25(+) or
      CD4(+)CD25(+)CCR4(+) cells and reduced the proviral loads (PVLs) in peripheral
      blood mononuclear cells (PBMCs). Importantly, TARC-PE38 significantly reduced the
      PVLs in PBMCs obtained from asymptomatic carriers. We show that the cytotoxicity
      of TARC-PE38 is mediated by the expression of the proprotein convertase, furin.
      The expression of furin was enhanced in HTLV-1-infected cells and correlated
      positively with PVLs in HTLV-1-infected individuals, suggesting that infected
      cells are more susceptible to TARC-PE38 than normal cells. CONCLUSIONS: TARC-PE38
      robustly controls HTLV-1 infection by eliminating infected cells in both a CCR4-
      and furin-dependent manner, indicating the excellent therapeutic potential of
      TARC-PE38.

PMID- 26289729
TI  - Plasticity and ductility in graphene oxide through a mechanochemically induced
      damage tolerance mechanism.
AB  - The ability to bias chemical reaction pathways is a fundamental goal for chemists
      and material scientists to produce innovative materials. Recently, two
      dimensional materials have emerged as potential platforms for exploring novel
      mechanically activated chemical reactions. Here we report a mechanochemical
      phenomenon in graphene oxide membranes, covalent epoxide-to-ether functional
      group transformations that deviate from epoxide ring-opening reactions,
      discovered through nanomechanical experiments and density functional-based tight
      binding calculations. These mechanochemical transformations in a two-dimensional
      system are directionally dependent, and confer pronounced plasticity and damage
      tolerance to graphene oxide monolayers. Additional experiments on chemically
      modified graphene oxide membranes, with ring-opened epoxide groups, verify this
      unique deformation mechanism. These studies establish graphene oxide as a two
      dimensional building block with highly tuneable mechanical properties for the
      design of high-performance nanocomposites, and stimulate the discovery of new
      bond-selective chemical transformations in two-dimensional materials. 

PMID- 26289730
TI  - Beyond the Frozen Accident: Glycine Assignment in the Genetic Code.
AB  - tRNA with a terminal UCCA-3' forms a structure in which the 3'-sequence folds
      back. The adenine of glycyl-AMP can base-pair with the uridine of the UCCA-3'
      region, which places the glycine residue in close proximity to the 3'-terminal
      adenosine of tRNA, possibly enabling the transfer of glycine from glycyl-AMP to
      tRNA. Thus, the UCCA-3'-containing tRNA (as seen in eubacterial tRNA(Gly)s) would
      possess an intrinsic property of glycylation by glycyl-AMP. This model provides a
      new perspective on the origins of the glycine assignment in the genetic code,
      beyond the "frozen accident" hypothesis. 

PMID- 26289731
TI  - Cancer Molecular Evolution.

PMID- 26289732
TI  - The economic impact of symptomatic menopause among low-socioeconomic women in the
      United States.
AB  - BACKGROUND: Menopausal symptoms have a significant negative impact on patient's
      quality of life and increase healthcare costs among women. METHODS: This
      retrospective analysis used data from a U.S. national database (01 January 2008
      31 December 2010). Patients with a diagnosis of menopause symptoms or a
      prescription claim for hormone therapy were matched to control patients.
      Healthcare resource utilization and costs during the 6-month follow-up period
      were compared. Generalized linear models were used to adjust for differences in
      baseline and demographic characteristics between the cohorts. RESULTS: A total of
      71,076 patients were included in each cohort. Patients with menopausal symptoms
      were more likely to have depression and anxiety and incurred significantly higher
      follow-up healthcare costs ($7237 vs $6739, p < 0.001) and healthcare utilization
      during the 6-month follow-up period. CONCLUSION: Patients diagnosed with
      menopausal symptoms or treated with hormone therapy incurred significantly higher
      healthcare costs than those without menopausal symptoms or treatment.

PMID- 26289734
TI  - The cost-effectiveness of novel direct acting antiviral agent therapies for the
      treatment of chronic hepatitis C.
AB  - In the USA, over 3 million individuals are infected with the HCV and 75-85% of
      them have or will develop chronic hepatitis C (CHC) which can lead to serious
      consequences such as liver cirrhosis, cancer and death. The old standard of care
      for the treatment of CHC was Pegylated-Interferon + Ribavirin with or without a
      protease inhibitor such as Boceprevir/Telaprevir. These treatments had a cure
      rate or rate of sustained virologic response of 66-80%. Since the close of 2013,
      several new direct acting antiviral agents (DAAs) for the treatment of CHC have
      been approved by the US FDA and have entered the US drug market. These novel CHC
      treatments boast very high cure rates of 80-100% and come with matching high
      price tags. Costs of CHC regimens that contain these novel DAAs range from
      $63,000 to $168,000 per treatment course. Using electronic databases, studies
      evaluating the cost-effectiveness of novel CHC treatments in USA were reviewed,
      and the reported incremental cost-effectiveness ratios based on cost per
      additional quality adjusted life year gained from the studies reviewed indicated
      that some novel DAA regimens are cost-effective; however, cost-effectiveness is
      contingent upon a variety of factors such as HCV genotype (1-4), presence of
      liver cirrhosis, patient treatment history and willingness-to-pay thresholds. 

PMID- 26289733
TI  - Personalized medicine and economic evaluation in oncology: all theory and no
      practice?
AB  - The clinical definition of personalized medicine (PM) is closely related to that
      of pharmacogenomics. Ideally, PM could lead the pharmaceutical industry to
      differentiate products by subgroups of patients with the same pathology and find
      new gene targets for drug discovery. Here, we focus on the potential impact of PM
      on the design of clinical trials and economic evaluations limited to oncology
      (its first and main field of application). Then, we assess the European economic
      evaluations focused on trastuzumab and cetuximab, the two drugs usually mentioned
      as emblematic examples of targeted therapies. Clinical results of PM in oncology
      have not been as encouraging as hoped so far. Of course, economic evaluations on
      targeted therapies cannot help overcome the lack of clinical evidence for most of
      them. The two paradigmatic examples of cetuximab and trastuzumab indicate that
      the methodological implications on economic evaluations debated in the literature
      are more theoretical than practical. 

PMID- 26289735
TI  - Economic evaluation alongside factorial trials: a systematic review of empirical
      studies.
AB  - Although economic evaluations have been performed alongside factorial trials,
      there seems to be limited guidance/consensus on appropriate methods of analysis.
      Following Centre for Review and Dissemination guidance, a systematic review of
      published literature for all years was performed to explore how economic
      evaluation alongside factorial trials have been conducted and only full economic
      evaluations conducted alongside factorial trials were included. A total of 16
      relevant studies were identified, and an assessment of these indicated that two
      methods: within-the-table and at-the-margins approaches were used for the
      analysis. With the exception of one study, all others did not consider
      interactions in costs and outcomes or give a detailed explanation of why a
      particular approach was adopted. The authors recommend that additional guidance
      is needed, and further research is required to evaluate the impact of alternative
      methods on policy recommendations and establish good practice methods for the
      economic analysis of factorial trials. 

PMID- 26289736
TI  - Economic resources consumption structure in severe hypoglycemia episodes: a
      systematic review and meta-analysis.
AB  - Diabetes mellitus (DM) is associated with severe hypoglycemia events (SHEs) that
      vary in severity and resource consumption. Here we perform a systematic review in
      Medline of studies evaluating SHE-related health resource use. Eligible studies
      investigated patients with DM and included >=10 SHEs. We also assessed studies
      identified in another systematic review, and through references from the included
      studies. We identified 14 relevant studies and used data from 11 (encompassing
      6075 patients). Study results were interpreted to fit our definitions, which
      sometimes required assumptions. SHE type structure was synthesized using Bayesian
      modeling. Estimating Type 1 & 2 DM separately revealed only small differences;
      therefore, we used joint results. Of the analyzed SHEs, 9.97% were hospital
      treated, 22.3% medical professional-treated, and 67.73% family-treated. These
      meta-analysis results help in understanding the structure of resource consumption
      following SHE and can be used in economic studies. 

PMID- 26289737
TI  - 'The patient': at the center of patient-reported outcomes.
AB  - The recent emphasis of including patient reports in their own care management is
      reviewed in terms of the factors that contributed to its popularity. The role
      change of patients as being active participants in their own care as a result of
      the rising consumerism and advocacy has led to increased pressures for including
      patients in the therapeutic decision-making process. As consumers of clinical
      services, their perspectives and attitudes towards health and illness acquired
      more importance. The rising cost of healthcare has added another dimension in
      cost containment by empowering patients and sharing responsibility in their
      recovery, which hopefully can improve outcomes. Challenges in the development and
      implementation of patient-reported outcomes in psychiatry are reviewed and
      include the still unresolved subjective/objective dichotomy, identification of
      the most appropriate and relevant patient-reported outcomes. Few outcomes are
      identified and include: subjective tolerability of medication, self-reported
      health-related quality of life, preferences, patients' attitudes towards health
      and illness, satisfaction with medication and overall satisfaction of quality of
      care, and functional state, with particular focus on social functioning. 

PMID- 26289738
TI  - Aspirin inhibits hepatitis C virus entry by downregulating claudin-1.
AB  - Aspirin has previously been reported to inhibit hepatitis C virus (HCV)
      replication. The aim of this study was to investigate whether aspirin is involved
      in blocking HCV entry. We found that aspirin inhibits the entry of HCVpp and
      infectious HCV. The level of claudin-1, an HCV receptor, is reduced by aspirin.
      Our results extend the anti-HCV effect of aspirin to the HCV entry step and
      further reinforce the anti-HCV role of aspirin. 

PMID- 26289739
TI  - The role of intra-domain disulfide bonds in heat-induced irreversible
      denaturation of camelid single domain VHH antibodies.
AB  - Camelid-derived single domain VHH antibodies are highly heat resistant, and the
      mechanism of heat-induced VHH denaturation predominantly relies on the chemical
      modification of amino acids. Although chemical modification of disulfide bonds
      has been recognized as a cause for heat-induced denaturation of many proteins,
      there have been no mutagenesis studies, in which the number of disulfide bonds
      was controlled. In this article, we examined a series of mutants of two different
      VHHs with single, double or no disulfide bonds, and scrutinized the effects of
      these disulfide bond modifications on VHH denaturation. With the exception of one
      mutant, the heat resistance of VHHs decreased when the number of disulfide bonds
      increased. The effect of disulfide bonds on heat denaturation was more striking
      if the VHH had a second disulfide bond, suggesting that the contribution of
      disulfide shuffling is significant in proteins with multiple disulfide bonds.
      Furthermore, our results directly indicate that removal of a disulfide bond can
      indeed increase the heat resistance of a protein, irrespective of the negative
      impact on equilibrium thermodynamic stability. 

PMID- 26289740
TI  - Encapsulated Silicene: A Robust Large-Gap Topological Insulator.
AB  - The quantum spin Hall (QSH) effect predicted in silicene has raised exciting
      prospects of new device applications compatible with current microelectronic
      technology. Efforts to explore this novel phenomenon, however, have been impeded
      by fundamental challenges imposed by silicene's small topologically nontrivial
      band gap and fragile electronic properties susceptible to environmental
      degradation effects. Here we propose a strategy to circumvent these challenges by
      encapsulating silicene between transition-metal dichalcogenides (TMDCs) layers.
      First-principles calculations show that such encapsulated silicene exhibit a two
      orders-of-magnitude enhancement in its nontrivial band gap, which is driven by
      the strong spin-orbit coupling effect in TMDCs via the proximity effect.
      Moreover, the cladding TMDCs layers also shield silicene from environmental gases
      that are detrimental to the QSH state in free-standing silicene. The encapsulated
      silicene represents a novel two-dimensional topological insulator with a robust
      nontrivial band gap suitable for room-temperature applications, which has
      significant implications for innovative QSH device design and fabrication. 

PMID- 26289741
TI  - Assessing Risk and Preventing 30-Day Readmissions in Decompensated Heart Failure:
      Opportunity to Intervene?
AB  - Heart failure (HF) patients are at high risk of hospital readmission, which
      contributes to substantial health care costs. There is great interest in
      strategies to reduce rehospitalization for HF. However, many readmissions occur
      within 30 days of initial hospital discharge, presenting a challenge for
      interventions to be instituted in a short time frame. Potential strategies to
      reduce readmissions for HF can be classified into three different forms. First,
      patients who are at high risk of readmission can be identified even before their
      initial index hospital discharge. Second, ambulatory remote monitoring strategies
      may be instituted to identify early warning signs before acute decompensation of
      HF occurs. Finally, strategies may be employed in the emergency department to
      identify low-risk patients who may not need hospital readmission. If symptoms
      improve with initial therapy, low-risk patients could be referred to specialized,
      rapid outpatient follow-up care where investigations and therapy can occur in an
      outpatient setting.

PMID- 26289742
TI  - The association between seasonal asthma exacerbations and viral respiratory
      infections in a pediatric population receiving inhaled corticosteroid therapy
      with or without long-acting beta-adrenoceptor agonist: a randomized study.
AB  - BACKGROUND: A seasonal peak in asthma exacerbations in the fall has previously
      been reported. The association between fall exacerbations and viral respiratory
      tract infections (RTI) remains uncertain. OBJECTIVE: To investigate the number of
      fall exacerbations and the incidence of RTIs in a pediatric asthmatic population
      using an at-home mucus collection methodology. METHODS: This was a 16-week,
      multicenter, randomized, double-blind, parallel-group exploratory study.
      Children, 4-11 years of age with a clinical diagnosis of asthma requiring use of
      an inhaled corticosteroid, a morning peak expiratory flow >=70% predicted and a
      history of >=1 asthma exacerbation during the previous respiratory viral season
      were eligible for enrollment. Subjects were randomized (1:1) to receive
      fluticasone propionate/salmeterol (FP/SAL) 100/50 mcg or FP 100 mcg prior to
      starting school. Subjects collected mucus samples using an at-home kit when they
      experienced respiratory symptoms. Mucus samples obtained during symptomatic
      periods were analyzed for common respiratory viruses by multiplex polymerase
      chain reaction. The number of exacerbations requiring systemic corticosteroids
      was recorded. RESULTS: In total, 339 (FP/SAL, n = 171; FP, n = 168) subjects were
      randomized and included in the intent-to-treat population; 292 (86%) completed
      the study. Of the 537 mucus samples collected, 64% tested positive for viruses,
      but only 6% of positive samples were associated with an asthma exacerbation.
      Exacerbations were infrequent, with only 41 subjects reporting 49 exacerbations
      in total. Adverse events were reported in 66% of subjects. CONCLUSIONS: In a
      susceptible population, the fall asthma exacerbation rates in children were low
      despite frequent detection of viral RTIs. NCT01192178; GSK ID: ADA113872.

PMID- 26289743
TI  - Direct in situ measurement of specific capacitance, monolayer tension, and
      bilayer tension in a droplet interface bilayer.
AB  - Thickness and tension are important physical parameters of model cell membranes.
      However, traditional methods to measure these quantities require multiple
      experiments using separate equipment. This work introduces a new multi-step
      procedure for directly accessing in situ multiple physical properties of droplet
      interface bilayers (DIB), including specific capacitance (related to thickness),
      lipid monolayer tension in the Plateau-Gibbs border, and bilayer tension. The
      procedure employs a combination of mechanical manipulation of bilayer area
      followed by electrowetting of the capacitive interface to examine the
      sensitivities of bilayer capacitance to area and contact angle to voltage,
      respectively. These data allow for determining the specific capacitance of the
      membrane and surface tension of the lipid monolayer, which are then used to
      compute bilayer thickness and tension, respectively. The use of DIBs affords
      accurate optical imaging of the connected droplets in addition to electrical
      measurements of bilayer capacitance, and it allows for reversibly varying bilayer
      area. After validating the accuracy of the technique with diphytanoyl
      phosphatidylcholine (DPhPC) DIBs in hexadecane, the method is applied herein to
      quantify separately the effects on membrane thickness and tension caused by
      varying the solvent in which the DIB is formed and introducing cholesterol into
      the bilayer. Because the technique relies only on capacitance measurements and
      optical images to determine both thickness and tension, this approach is
      specifically well-suited for studying the effects of peptides, biomolecules,
      natural and synthetic nanoparticles, and other species that accumulate within
      membranes without altering bilayer conductance. 

PMID- 26289744
TI  - Role of growth hormone in maturation and activation of dendritic cells via miR
      200a and the Keap1/Nrf2 pathway.
AB  - OBJECTIVES: Dendritic cells (DCs) are antigen-presenting cells that participate
      in the immune response; recently, it has been reported that growth hormone (GH)
      promotes their maturation. The aim of this study was to investigate mechanisms by
      which GH acts on DC maturation and activation. MATERIALS AND METHODS: Human
      peripheral blood monocytes (HPBMs) were induced to become immature DCs and
      treated with GH to obtain mature DCs. An osteosarcoma mouse model was established
      by injection of LM8 cells to investigate anti-tumour effect of GH-induced DCs in
      vivo. RESULTS: After administration of GH, DCs reduced miR-200a expression and
      nuclear Nrf2 accumulation; miR-200a down-regulation inhibited DC maturation. Nrf2
      ubiquitination level was increased by Keap1 overexpression in murine bone marrow
      derived dendritic cells (BMDCs), which was cancelled by miR-200a in GH exposed
      cells. In vivo, tumour volume was significantly reduced by GH-treated DCs and the
      effect was reversed by overexpression of miR-200a. CONCLUSIONS: GH promoted
      maturation and activation of DCs, and regulation of miR-200a played a part in
      this process by modulation of the Keap1/Nrf2 pathway.

PMID- 26289745
TI  - Effect of dietary cation-anion difference on ruminal metabolism, total apparent
      digestibility, blood and renal acid-base regulation in lactating dairy cows.
AB  - The present study aimed to evaluate the effect of dietary cation-anion difference
      (DCAD) on ruminal fermentation, total apparent digestibility, blood and renal
      metabolism of lactating dairy cows. Sixteen Holstein cows were distributed in
      four contemporary 4*4 Latin Square designs, which consisted of four periods of 21
      days and four treatments according to DCAD: +290; +192; +98 and -71
      milliequivalent (mEq)/kg dry matter (DM). Ruminal pH and concentrations of acetic
      and butyric acid increased linearly according to the increase of DCAD. Similarly,
      NDF total apparent digestibility linearly increased by 6.38% when DCAD increased
      from -71 to 290 mEq/kg DM [Y=65.90 (SE=2.37)+0.0167 (SE=0.0068)*DCAD (mEq/kg
      DM)]. Blood pH was also increased according to DCAD, which resulted in reduction
      of serum concentrations of Na, K and ionic calcium (iCa). To maintain the blood
      acid-base homeostasis, renal metabolism played an important role in controlling
      serum concentrations of Na and K, since the Na and K urinary excretion increased
      linearly by 89.69% and 46.06%, respectively, from -71 to 290 mEq/kg DM. Changes
      in acid-base balance of biological fluids may directly affect the mineral
      composition of milk, as milk concentrations of Na, K, iCa and chlorides were
      reduced according to blood pH increased. Thus, it can be concluded that the
      increase of DCAD raises the pH of ruminal fluid, NDF total apparent
      digestibility, and blood pH, and decreases the milk concentration of cationic
      minerals, as well as the efficiency of Na utilization to milk production. 

PMID- 26289746
TI  - Impact of ethnicity on mood disorders in Parkinson's disease.
AB  - Anxiety and depression are common in Parkinson's disease (PD) patients, yet their
      prevalence and severity compared to individuals without PD requires more
      research. Moreover, it has never been compared across different ethnic groups.
      The objective of this study was to close that gap in the literature by exploring
      the caseness and severity of anxiety and depression in PD patients of different
      ethnicities compared to controls without PD. It was found that caseness and
      severity of anxiety and depression are higher in individuals with PD compared to
      controls. Furthermore, the caseness and severity of anxiety and depression do not
      vary significantly among ethnic groups. Finally, depression caseness was not
      predicted by age, gender, disease duration, restless legs syndrome prevalence,
      Hoehn and Yahr (H&Y) score nor Unified Parkinson's disease rating scale part III
      (UPDRS-III) score. Anxiety caseness was predicted by gender, with females 2.7
      times more likely to have anxiety caseness than males. Overall, our study
      suggests that treatment plans should be individualized based on prevalence and
      severity of the two conditions in individuals with PD rather than generalize
      treatment for specific ethnic groups. 

PMID- 26289747
TI  - Logical Inconsistencies in 3 Preference Elicitation Methods for EQ-5D Health
      States: A Study in the Brazilian Population.
AB  - BACKGROUND: . Logical inconsistency for health states preferences occurs when one
      logically worse health state, in terms of quality of life, is ranked higher than
      a logically better health state. OBJECTIVE: . This study explores the presence of
      inconsistent responses for the EQ-5D health states valuations in a Brazilian
      population survey. It compares the level of inconsistency in 3 preference-based
      methods: ranking, visual analog scale (VAS), and time tradeoff (TTO). The
      influence of EQ-5D health state descriptions is explored by examining the
      distance between states using a city-block metric as an indicator of proximity.
      Moreover, it examines the association between formal education and the presence
      of inconsistencies, as well as the effect of removing inconsistent respondents on
      the estimation of social value sets from TTO and VAS. METHODS: . Data came from a
      valuation study with 3362 literate individuals aged between 18 and 64 years
      living in urban areas of Minas Gerais state, Brazil. Logical inconsistency was
      assessed using the percentage of inconsistent respondents and inconsistency rate.
      A logistic model was estimated to assess the association between formal education
      and the logical inconsistency. Societal preferences were estimated excluding
      inconsistent respondents considering city-block metric. RESULTS: . The percentage
      of inconsistent respondents and inconsistency rate are similar for TTO and
      ranking and lower for VAS. The probability of being inconsistent is higher among
      less educated groups in ranking and TTO. Inconsistency decreases with distance
      for all 3 methods. The removal of inconsistent individuals by considering city
      block distance improves TTO estimation of social value sets. CONCLUSION: .
      Findings suggest that removal of inconsistencies in TTO should consider city
      block distance. For VAS, inconsistencies are not associated with formal education
      and do not affect social value set estimation.

PMID- 26289748
TI  - Understanding of Surface Redox Behaviors of Li2MnO3 in Li-Ion Batteries: First
      Principles Prediction and Experimental Validation.
AB  - Critical degradation mechanism of many cathode materials for Li-ion batteries is
      closely related to phase transformations at the surface/interface. Li2MnO3 in x
      Li2MnO3 ?(1-x) LiMO2 (M=Ni, Co, Mn) provides high capacity, but the Li2MnO3 phase
      is known to degrade during cycling through phase transformation and O2 evolution.
      To resolve such degradation problems, it is critical to develop a fundamental
      understanding of the underlying mechanism. Using first-principles calculations,
      we identified the surface delithiation potential (<4.5 V vs. Li/Li(+) ) of
      Li2MnO3, which is significantly lower than the bulk redox potential. A lower Mn
      oxidation state at the surface would reduce the delithiation potential compared
      with the fully oxidized Mn(4+) in the bulk. As a result, the delithiation would
      be initiated from the surface, which induces a phase transformation of Li2MnO3
      into a spinel-like structure from the surface. These theoretical findings have
      been confirmed by experimental analyses. Based on these detailed mechanistic
      understanding, it would be possible to develop rational approaches to modify and
      coat the surface to suppress degradation mechanisms.

PMID- 26289749
TI  - Ferroelectric-like metallic state in electron doped BaTiO3.
AB  - We report that a ferroelectric-like metallic state with reduced anisotropy of
      polarization is created by the doping of conduction electrons into BaTiO3, on the
      bases of x-ray/electron diffraction and infrared spectroscopic experiments. The
      crystal structure is heterogeneous in nanometer-scale, as enabled by the reduced
      polarization anisotropy. The enhanced infrared intensity of soft phonon along
      with the resistivity reduction suggests the presence of unusual electron-phonon
      coupling, which may be responsible for the emergent ferroelectric structure
      compatible with metallic state. 

PMID- 26289753
TI  - Iron-induced reactive oxygen species mediate transporter DMT1 endocytosis and
      iron uptake in intestinal epithelial cells.
AB  - Recent evidence shows that iron induces the endocytosis of the iron transporter
      dimetal transporter 1 (DMT1) during intestinal absorption. We, and others, have
      proposed that iron-induced DMT1 internalization underlies the mucosal block
      phenomena, a regulatory response that downregulates intestinal iron uptake after
      a large oral dose of iron. In this work, we investigated the participation of
      reactive oxygen species (ROS) in the establishment of this response. By means of
      selective surface protein biotinylation of polarized Caco-2 cells, we determined
      the kinetics of DMT1 internalization from the apical membrane after an iron
      challenge. The initial decrease in DMT1 levels in the apical membrane induced by
      iron was followed at later times by increased levels of DMT1. Addition of Fe(2+),
      but not of Cd(2+), Zn(2+), Cu(2+), or Cu(1+), induced the production of
      intracellular ROS, as detected by 2',7'-dichlorofluorescein (DCF) fluorescence.
      Preincubation with the antioxidant N-acetyl-l-cysteine (NAC) resulted in
      increased DMT1 at the apical membrane before and after addition of iron.
      Similarly, preincubation with the hydroxyl radical scavenger dimethyl sulfoxide
      (DMSO) resulted in the enhanced presence of DMT1 at the apical membrane. The
      decrease of DMT1 levels at the apical membrane induced by iron was associated
      with decreased iron uptake rates. A kinetic mathematical model based on
      operational rate constants of DMT1 endocytosis and exocytosis is proposed. The
      model qualitatively captures the experimental observations and accurately
      describes the effect of iron, NAC, and DMSO on the apical distribution of DMT1.
      Taken together, our data suggest that iron uptake induces the production of ROS,
      which modify DMT1 endocytic cycling, thus changing the iron transport activity at
      the apical membrane. 

PMID- 26289750
TI  - Targeting Wnt signaling in colorectal cancer. A Review in the Theme: Cell
      Signaling: Proteins, Pathways and Mechanisms.
AB  - The evolutionarily conserved Wnt signaling pathway plays essential roles during
      embryonic development and tissue homeostasis. Notably, comprehensive genetic
      studies in Drosophila and mice in the past decades have demonstrated the crucial
      role of Wnt signaling in intestinal stem cell maintenance by regulating
      proliferation, differentiation, and cell-fate decisions. Wnt signaling has also
      been implicated in a variety of cancers and other diseases. Loss of the Wnt
      pathway negative regulator adenomatous polyposis coli (APC) is the hallmark of
      human colorectal cancers (CRC). Recent advances in high-throughput sequencing
      further reveal many novel recurrent Wnt pathway mutations in addition to the well
      characterized APC and beta-catenin mutations in CRC. Despite attractive
      strategies to develop drugs for Wnt signaling, major hurdles in therapeutic
      intervention of the pathway persist. Here we discuss the Wnt-activating
      mechanisms in CRC and review the current advances and challenges in drug
      discovery. 

PMID- 26289751
TI  - The connexin 43/ZO-1 complex regulates cerebral endothelial F-actin architecture
      and migration.
AB  - Endothelial cell migration is a fundamental process during angiogenesis and,
      therefore, a point of intervention for therapeutic strategies aimed at
      controlling pathologies involving blood vessel growth. We sought to determine the
      role of the gap junction protein connexin 43 (Cx43) in key features of
      angiogenesis in the central nervous system. We used an in vitro model to test the
      hypothesis that a complex of interacting proteins, including Cx43 and zonula
      occludens-1 (ZO-1), regulates the migratory behavior of cerebral endothelium.
      With knockdown and overexpression experiments, we demonstrate that the rate of
      healing following scrape-wounding of endothelium is regulated by the level of
      Cx43 protein expression. The effects on cell motility and proliferation were
      independent of gap junction communication as cells were sensitive to altered Cx43
      expression in single plated cells. Coupling of Cx43/ZO-1 critically regulates
      this process as demonstrated with the use of a Cx43 alpha-carboxy terminus 1
      peptide mimetic (alphaCT1) and overexpression of a mutant ZO-1 with the Cx43
      binding PDZ2 domain deleted. Disrupting the Cx43/ZO-1 complex with these
      treatments resulted in collapse of the organized F-actin cytoskeleton and the
      appearance of actin nodes. Preincubation with the myosin 2 inhibitors
      blebbistatin or Y-27632 disrupted the Cx43/ZO-1 complex and inhibited cell
      spreading at the leading edge of migration. Cells studied individually in time
      lapse open field locomotion assays wandered less when Cx43/ZO-1 interaction was
      disrupted without significant change in speed, suggesting that faster wound
      healing is a product of linearized migration. In contrast to the breakdown of F
      actin architecture, microtubule architecture was not obviously affected by
      treatments. This study provides new insight into the fundamental regulatory
      mechanisms of cerebral endothelial cell locomotion. Cx43 tethers the F-actin
      cytoskeleton through a ZO-1 linker and supports cell spreading and exploration
      during locomotion. Here, we demonstrate that releasing this actin-coupled tether
      shifts the balance of directional migration control to a more linear movement
      that enhances the rate of wound healing.

PMID- 26289752
TI  - A new experimental model for force enhancement: steady-state and transient
      observations of the Drosophila jump muscle.
AB  - The increase in steady-state force after active lengthening in skeletal muscle,
      termed force enhancement (FE), has been observed for nearly one century. Although
      demonstrated experimentally at various structural levels, the underlying
      mechanism(s) remain unknown. We recently showed that the Drosophila jump muscle
      is an ideal model for investigating mechanisms behind muscle physiological
      properties, because its mechanical characteristics, tested thus far, duplicate
      those of fast mammalian skeletal muscles, and Drosophila has the advantage that
      it can be more easily genetically modified. To determine if Drosophila would be
      appropriate to investigate FE, we performed classic FE experiments on this
      muscle. Steady-state FE (FESS), following active lengthening, increased by 3, 7,
      and 12% of maximum isometric force, with increasing stretch amplitudes of 5, 10,
      and 20% of optimal fiber length (FLOPT), yet was similar for stretches across
      increasing stretch velocities of 4, 20, and 200% FLOPT/s. These FESS
      characteristics of the Drosophila jump muscle closely mimic those observed
      previously. Jump muscles also displayed typical transient FE characteristics. The
      transient force relaxation following active stretch was fit with a double
      exponential, yielding two phases of force relaxation: a fast initial relaxation
      of force, followed by a slower recovery toward steady state. Our analyses
      identified a negative correlation between the slow relaxation rate and FESS,
      indicating that there is likely an active component contributing to FE, in
      addition to a passive component. Herein, we have established the Drosophila jump
      muscle as a new and genetically powerful experimental model to investigate the
      underlying mechanism(s) of FE. 

PMID- 26289754
TI  - The transcriptome of Euglena gracilis reveals unexpected metabolic capabilities
      for carbohydrate and natural product biochemistry.
AB  - Euglena gracilis is a highly complex alga belonging to the green plant line that
      shows characteristics of both plants and animals, while in evolutionary terms it
      is most closely related to the protozoan parasites Trypanosoma and Leishmania.
      This well-studied organism has long been known as a rich source of vitamins A, C
      and E, as well as amino acids that are essential for the human diet. Here we
      present de novo transcriptome sequencing and preliminary analysis, providing a
      basis for the molecular and functional genomics studies that will be required to
      direct metabolic engineering efforts aimed at enhancing the quality and quantity
      of high value products from E. gracilis. The transcriptome contains over 30,000
      protein-encoding genes, supporting metabolic pathways for lipids, amino acids,
      carbohydrates and vitamins, along with capabilities for polyketide and non
      ribosomal peptide biosynthesis. The metabolic and environmental robustness of
      Euglena is supported by a substantial capacity for responding to biotic and
      abiotic stress: it has the capacity to deploy three separate pathways for vitamin
      C (ascorbate) production, as well as producing vitamin E (alpha-tocopherol) and,
      in addition to glutathione, the redox-active thiols nor-trypanothione and
      ovothiol.

PMID- 26289755
TI  - Body shape in terrestrial isopods: A morphological mechanism to resist
      desiccation?
AB  - Woodlice are fully terrestrial crustaceans and are known to be sensitive to water
      loss. Their half-ellipsoidal shapes represent simple models in which to
      investigate theoretical assumptions about organism morphology and rates of
      exchange with the environment. We examine the influence of surface area and mass
      on the desiccation rates in three eco-morphologically different species of
      woodlice: Oniscus asellus, Porcellio scaber, and Armadillidium vulgare. Our
      analysis indicates that the rate of water loss of an individual depends on both
      the initial weight and the body surface area. Interspecific and intraspecific
      analyses show that the mass-specific water loss rate of a species decreases along
      with the ratio of surface area to volume. In particular, we show that body shape
      explains the difference in mass-specific water loss rates between A. vulgare and
      P. scaber. This observation also explains several known ecological patterns, for
      example, the distribution and survivorship of individuals. However, in addition
      to body size and shape, water loss in terrestrial isopods depends also on the
      coefficient of permeability (i.e., a measure of water loss rate per surface
      unit), which is high in O. asellus and lower (and at similar levels) in P. scaber
      and A. vulgare. We discuss morphological, physiological, and behavioral aspects
      of water loss avoidance in terrestrial isopods.

PMID- 26289756
TI  - [A case of multiple sclerosis with bilateral intermediate uveitis].
AB  - We describe a case of 20-year-old woman with visual impairment in her left eye.
      Her left visual acuity was 0.07 and an ophthalmoscopic examination demonstrated
      bilateral intermediate uveitis (IU). A neurological examination on admission
      revealed lower nasal quadrantanopsia in her left eye and an exaggerated right
      patellar tendon reflex. A T2-weighted MRI showed multiple high-intensity lesions
      in the bilateral periventricular region, corpus callosum, medulla. A short T1
      inversion recovery MRI also showed a swollen left retrobulbar optic nerve and
      posterior thoracic cord lesion at Th 9 level. The latter longitudinal length was
      approximately 20 mm. Laboratory investigation demonstrated no abnormalities
      including an anti-aquaporin-4 antibody. A cerebrospinal fluid examination
      revealed an increased IgG-index (1.21) with oligoclonal IgG babds. Initially, a
      diagnosis of retrobulbar optic neuritis with IU was made. She received subtenon
      corticosteroid injection with intravenous methylprednisolone pulse and oral
      prednisolone therapy. An immediate improvement of her visual symptoms and MRI
      abnormalities was observed. Approximately 1 year later, a new high-intensity
      lesion in the right internal capsule was present on a follow-up T2-weighted brain
      MRI, established a diagnosis of multiple sclerosis (MS) based on the McDonald
      criteria in 2010. Previous reports in Japan demonstrated few cases of uveitis in
      patients with MS and this is the first report of MS with IU in Japan. 

PMID- 26289757
TI  - [A case of neuromyelitis optica spectrum disorder presenting with severe
      orthostatic hypotension].
AB  - The patient is a 68-year-old Japanese woman. She was admitted to our hospital due
      to continuous hiccups and vomiting episodes for more than one week. On
      examinations, muscle strength in her right lower limb was slightly decreased, and
      pyramidal tract signs were positive bilaterally. The fluid attenuated inversion
      recovery imaging of the brain showed lesions in the dorsal and lateral medulla.
      Serum anti-aquaporin 4 antibody was positive. We then diagnosed the patient with
      neuromyelitis optica spectrum disorder (NMOSD). Severe orthostatic hypotension
      (OH) was determined. While hiccups and vomiting improved gradually, OH lasted for
      more than three weeks. OH improved after administration of intravenous
      methylpredonisolone-pulse therapy. In this case, the lesion in the dorsal medulla
      might be responsible for OH. We considered that OH might be one of the symptoms
      of NMOSD. 

PMID- 26289758
TI  - [A case of pure alexia and foreign accent syndrome following acute encephalopathy
      in the presence of anti-glutamate receptor antibodies].
AB  - A 41-year-old right-handed woman presented abnormal behavior two weeks after
      suffering from headache and fever. Anti-glutamate receptor antibodies in the
      serum and cerebrospinal fluid were positive and we diagnosed anti-glutamate
      receptor antibody-related encephalopathy. The patient improved after
      administration of corticosteroid and was discharged without neurological deficit.
      After discharge, pure alexia and foreign accent syndrome-like language
      disturbance appeared consecutively. The serial fluorodeoxyglucose-positron
      emission tomography scans suggested that pure alexia and FAS-like language
      disturbance may have been caused by low function of the occipital lobes and the
      left frontal lobe, respectively. FAS has been linked to various lesions in the
      brain. The background mechanism may therefore be heterogeneous. On the other
      hand, patients with this syndrome recover spontaneously with our case. FAS may
      therefore be a temporal phenomenon resulting from imbalance in language
      processing rather than a specific deficit. 

PMID- 26289759
TI  - [A case of motor dominant neuropathy and focal segmental glomerulosclerosis
      associated with Sjogren's syndrome].
AB  - A 49-year-old woman was admitted to our hospital with gradually progressive
      weakness of the limbs for about 20 days. She presented with weakness of the
      limbs, predominantly in the proximal portion, and slight dysesthesia of the
      limbs, predominantly in the distal portion. Repeated nerve conduction examination
      revealed axonopathy dominantly in the motor neurons. Therefore, we suspected her
      as having Guillain-Barre syndrome, and initiated intravenous administration of
      high-dose immunoglobulin. However, her symptoms progressed gradually and finally
      she found it difficult to walk. Her urine analysis simultaneously demonstrated
      albuminuria, and a kidney biopsy indicated focal segmental glomerulosclerosis. At
      that point, laboratory examination showed high levels of anti SS-A antibody and
      salivary gland biopsy revealed infiltration of a significant number of
      lymphocytes around the gland, which led to the diagnosis of Sjogren's syndrome.
      We considered the etiology of the neural and renal dysfunction as due to the
      inflammatory mechanism associated with Sjogren's syndrome. Therefore, we
      administered a second course of immunoglobulin therapy and steroid therapy, which
      included both pulse and oral administration. Her neurologic symptoms and
      albuminuria improved rapidly after steroid therapy. The present case indicates
      that both motor dominant neuropathy and focal segmental glomerulosclerosis can
      occur in patients with Sjogren's syndrome. 

PMID- 26289760
TI  - [Small vessel disease associated with cranial irradiation].
AB  - We report two cases of young patients with lacunar stroke who demonstrated
      multiple microbleeds (MBs) a long period after cranial irradiation. Case 1: a 44
      year-old man developed dysarthria and left hemiparesis from a day before
      admission. Magnetic resonance imaging showed an acute lacunar infract in the
      right corona radiata. Case 2: a 28-year-old woman was admitted due to dysarthria
      and right hemiparesis. An acute lacunar infract was detected in the left corona
      radiata. T2* WI revealed multiple MBs in the region corresponding to the
      irradiation in both patients. Since these patients had no vascular risk factors
      except for smoking habit in the former one and dyslipidemia in the latter one. We
      speculated that lacunar stroke and MBs had resulted from past cranial
      irradiation. In addition to accelerated atherosclerosis of the large vessels,
      small vessel disease should be noted as an important long-term complication after
      cranial irradiation. 

PMID- 26289761
TI  - [A case of bilateral medial medullary infarction caused by unilateral vertebral
      artery dissection].
AB  - A 34-year-old man developed right neck pain. Several hours later, he felt
      numbness of his extremities and presented at our hospital. He developed right
      hemiparesis and hypoesthesia of the right extremities. A few hours later, upbeat
      nystagmus and dysarthria appeared along with a sensory disturbance that spread to
      all extremities, and right hemiparesis progressed to tetraplegia. Brain MR
      diffusion-weighted images revealed a high-intensity lesion in the bilateral
      medial medulla oblongata and we diagnosed this bilateral medial medullary
      infarction. Three dimentional CT angiography revealed dissection of the right VA.
      We administered intravenous argatroban, edaravone, glycerin and oral clopidogrel.
      He was assessed as having modified Rankin scale 4 and was transferred to another
      hospital for rehabilitation on day 30. When the medial medulla oblongata is
      supplied by the unilateral VA, a unilateral VA dissection can cause bilateral
      medial medullary infarction. 

PMID- 26289762
TI  - [A case of chronic progressive motor-dominant multiple mononeuritis associated
      with primary Sjogren's syndrome].
AB  - A 45-year-old female with a history of dry eyes presented with chronic
      progressive disturbance of her right finger extension, bilateral foot drops, and
      dysesthesia in the left lower leg. On admission, neurological examination
      revealed decreased tendon reflex in the right upper limb and bilateral lower
      limbs, and dysesthesia in the distal outer portions of the bilateral lower legs.
      Her vibration sensation was moderately diminished in both lower legs. Weakness
      ranging from moderate to severe was predominantly found in the muscles innervated
      by the radial (r > l), medial (r > l), ulnar (r > l), deep peroneal (r ? l),
      tibial (r < l), and medial planter nerves (r < l). Nerve conduction study showed
      asymmetrical axonal neuropathy, while chronic neurogenic changes were observed on
      needle electromyography. Cerebrospinal fluid analysis results were unremarkable,
      except for an elevated IgG index (1.53) and the presence of oligoclonal IgG
      bands. Seropositive anti-SS-A antibody and histological findings of the biopsied
      minor salivary gland, as well as the lack of other connective tissue disorders,
      indicated primary Sjogren syndrome (SjS). A left sural nerve biopsy showed
      inhomogeneous reductions in the myelinated fibers within fascicules, mild
      infiltration of CD8-positive T lymphocytes around small vessels, and no fibrinoid
      necrosis in the arteries. From these findings, the diagnosis of motor-dominant
      multiple mononeuritis associated with primary SjS was made. Therapy that
      comprised a single course of intravenous (IV) methylprednisolone (1 g for 3
      days), followed by oral prednisolone (60 mg/day) with gradual tapering, resulted
      in no amelioration of her symptoms. She then received IV immunoglobulin (0.4
      mg/kg/day for 5 days), which resulted in moderate improvement in the strength of
      several muscles and a reduction of CSF IgG index (0.89). A wide variety of
      peripheral nerve complications are documented in primary SjS. However, the
      present case is unique in the symptoms of chronic progressive, motor-dominant,
      multiple mononeuritic phenotype. 

PMID- 26289763
TI  - Diffuse Atherosclerosis of the Left Internal Mammary Artery.

PMID- 26289764
TI  - Does warming up improve surgical outcome in total hip arthroplasty?
AB  - PURPOSE: Warming up prior to surgery has been shown to enhance surgeons'
      performance during laparoscopic procedures. It is unknown whether or not warming
      up prior to total hip arthroplasty (THA) will have a similar effect on surgical
      outcome. METHODS: We retrospectively evaluated the effect of warming up on the
      intraoperative outcome of 82 patients who underwent a primary THA with identical
      implants. The patients were divided equally into two groups. Group 1 (first case
      of the day) served as "warm-up procedure," while Group 2 (second case of the day)
      was the "post-warm-up procedure." RESULTS: We found no statistically significant
      difference when we compared cup abduction and anteversion angles, femoral offset,
      postoperative LLD, stem alignment, hip center of rotation and femoral stem canal
      fill between the two groups (p > 0.05). CONCLUSION: Warming up prior to
      performing surgery does not make a difference for primary THA when performed by
      an experienced surgeon. However, these results may not reflect its effect on
      procedures that require fine motor skills or done by an orthopedic trainee or
      less experienced surgeons.

PMID- 26289765
TI  - Combined effect of donor and recipient risk on outcome after liver
      transplantation: Research of the Eurotransplant database.
AB  - Recently the Eurotransplant donor risk index (ET-DRI) was published, a model
      based on data from the Eurotransplant database that can be used for risk
      indication of liver donors within the Eurotransplant region. Because outcome
      after liver transplantation (LT) depends both on donor and recipient risk
      factors, a combined donor-recipient model (DRM) would give a more complete
      picture of the overall risk involved. All liver transplants in adult recipients
      from January 1, 2008 to December 31, 2010 in the Eurotransplant region were
      included. Risk factors in donors and recipients for failure-free (retransplant
      free) survival were analyzed in univariate and multivariate analyses. A
      simplified recipient risk index (sRRI) was constructed using all available
      recipient factors. A total of 4466 liver transplants were analyzed. Median donor
      risk index and ET-DRI were 1.78 and 1.91, respectively. The ET-DRI was validated
      in this new cohort (P < 0.001; concordance index [c-index], 0.59). After
      construction of a simplified recipient risk index of significant recipient
      factors, Cox regression analysis showed that the combination ET-DRI and sRRI into
      a new DRM gave the highest predictive value (P < 0.001; c-index, 0.62). The
      combined model of ET-DRI and sRRI gave a significant prediction of outcome after
      orthotopic LT in the Eurotransplant region, better than the ET-DRI alone. This
      DRM has potential in comparing data in the literature and correcting for
      sickness/physical condition of transplant recipients. It is a first step toward
      benchmarking of graft survival in the Eurotransplant region.

PMID- 26289766
TI  - Effect of honey on the reproductive system of male rat offspring exposed to
      prenatal restraint stress.
AB  - Exposure to prenatal stress is associated with impaired reproductive function in
      male rat offspring. Honey is traditionally used by the Malays for enhancement of
      fertility. The aim of this study was to determine the effect of honey on
      reproductive system of male rat offspring exposed to prenatal restraint stress.
      Dams were divided into four groups (n = 10/group): control, honey, stress and
      honey + stress groups. Dams from honey and honey + stress groups received oral
      honey (1.2 g kg(-1) body weight) daily from day 1 of pregnancy, meanwhile dams
      from stress and honey + stress groups were subjected to restraint stress (three
      times per day) from day 11 of pregnancy until delivery. At 10 weeks old, each
      male rat offspring was mated with a regular oestrus cycle female. Male sexual
      behaviour and reproductive performance were evaluated. Then, male rats were
      euthanised for assessment on reproductive parameters. Honey supplementation
      during prenatal restraint stress significantly increased testis and epididymis
      weights as well as improved the percentages of abnormal spermatozoa and sperm
      motility in male rat offspring. In conclusion, this study might suggest that
      supplementation of honey during pregnancy seems to reduce the adverse effects of
      restraint stress on reproductive organs weight and sperm parameters in male rat
      offspring. 

PMID- 26289768
TI  - Cardiac resynchronization revisited: what is the next step?

PMID- 26289767
TI  - Early treatment with atorvastatin exerts parenchymal and vascular protective
      effects in experimental cerebral ischaemia.
AB  - BACKGROUND AND PURPOSE: From the clinical and experimental data available,
      statins appear to be interesting drug candidates for preventive neuroprotection
      in ischaemic stroke. However, their acute protective effect is, as yet,
      unconfirmed. EXPERIMENTAL APPROACH: Male C57Bl6/JRj mice were subjected to middle
      cerebral artery occlusion and treated acutely with atorvastatin (10-20 mg.kg(-1)
      day(-1) ; 24 or 72 h). Functional recovery (neuroscore, forelimb gripping
      strength and adhesive removal test) was assessed during follow-up and lesion
      volume measured at the end. Vasoreactivity of the middle cerebral artery (MCA),
      type IV collagen and FITC-dextran distribution were evaluated to assess
      macrovascular and microvascular protection. Activated microglia, leucocyte
      adhesion and infiltration were chosen as markers of inflammation. KEY RESULTS:
      Acute treatment with atorvastatin provided parenchymal and cerebral protection
      only at the higher dose of 20 mg.kg(-1) .day(-1) . In this treatment group,
      functional recovery was ameliorated, and lesion volumes were reduced as early as
      24 h after experimental stroke. This was associated with vascular protection as
      endothelial function of the MCA and the density and patency of the microvascular
      network were preserved. Acute atorvastatin administration also induced an anti
      inflammatory effect in association with parenchymal and vascular mechanisms; it
      reduced microglial activation, and decreased leucocyte adhesion and infiltration.
      CONCLUSIONS AND IMPLICATIONS: Acute atorvastatin provides global cerebral
      protection, but only at the higher dose of 20 mg.kg(-1) .day(-1) ; this was
      associated with a reduction in inflammation in both vascular and parenchymal
      compartments. Our results suggest that atorvastatin could also be beneficial when
      administered early after stroke.

PMID- 26289769
TI  - Recognizing the impact of ambient air pollution on skin health.
AB  - Ambient air pollution is a known public health hazard that negatively impacts non
      cutaneous organs; however, our knowledge regarding the effects on skin remains
      limited. Current scientific evidence suggests there are four mechanisms by which
      ambient air pollutants cause adverse effects on skin health: (i) generation of
      free radicals, (ii) induction of inflammatory cascade and subsequent impairment
      of skin barrier, (iii) activation of the aryl hydrocarbon receptor (AhR) and (iv)
      alterations to skin microflora. In this review, we provide a comprehensive
      overview on ambient air pollutants and their relevant sources, and highlight
      current evidence of the effects on skin. 

PMID- 26289770
TI  - Accessory cells for beta-cell transplantation.
AB  - Despite recent advances, insulin therapy remains a treatment, not a cure, for
      diabetes mellitus with persistent risk of glycaemic alterations and life
      threatening complications. Restoration of the endogenous beta-cell mass through
      regeneration or transplantation offers an attractive alternative. Unfortunately,
      signals that drive beta-cell regeneration remain enigmatic and beta-cell
      replacement therapy still faces major hurdles that prevent its widespread
      application. Co-transplantation of accessory non-islet cells with islet cells has
      been shown to improve the outcome of experimental islet transplantation. This
      review will highlight current travails in beta-cell therapy and focuses on the
      potential benefits of accessory cells for islet transplantation in diabetes. 

PMID- 26289771
TI  - Ovarian tumors related to intronic mutations in DICER1: a report from the
      international ovarian and testicular stromal tumor registry.
AB  - Germline DICER1 mutations have been described in individuals with pleuropulmonary
      blastoma (PPB), ovarian Sertoli-Leydig cell tumor (SLCT), sarcomas, multinodular
      goiter, thyroid carcinoma, cystic nephroma and other neoplastic conditions. Early
      results from the International Ovarian and Testicular Stromal Tumor Registry show
      germline DICER1 mutations in 48 % of girls and women with SLCT. In this report, a
      young woman presented with ovarian undifferentiated sarcoma. Four years later,
      she presented with SLCT. She was successfully treated for both malignancies.
      Sequence results showed a germline intronic mutation in DICER1. This mutation
      results in an exact duplication of the six bases at the splice site at the intron
      23 and exon 24 junction. Predicted improper splicing leads to inclusion of 10
      bases of intronic sequence, frameshift and premature truncation of the protein
      disrupting the RNase IIIb domain. A second individual with SLCT was found to have
      an identical germline mutation. In each of the ovarian tumors, an additional
      somatic mutation in the RNase IIIb domain of DICER1 was found. In rare patients,
      germline intronic mutations in DICER1 that are predicted to cause incorrect
      splicing can also contribute to the pathogenesis of SLCT.

PMID- 26289773
TI  - A start-up of psychrophilic anaerobic sequence batch reactor digesting a 35 %
      total solids feed of dairy manure and wheat straw.
AB  - Zero liquid discharge is currently an objective in livestock manure management to
      minimize water pollution. This paper reports the start-up phase of a novel
      psychrophilic (20  degrees C) dry anaerobic digestion of dairy manure with
      bedding fed at 35 % total solids and an organic loading rate of 3.0 g total
      chemical oxygen demand kg(-1) inoculum day(-1) in anaerobic sequence batch
      reactors. The specific methane (CH4) yield ranged from 165.4 +/- 9.8 to 213.9 +/-
      13.6 NL CH4 kg(-1) volatile solids (VS) with an overall average of 188 +/- 17 NL
      CH4 kg(-1) VS during 11 successive start-up cycles (231 days) and a maximum CH4
      production rate of 10.2 +/- 0.6 NL CH4 kg(-1) VS day(-1). The inoculum-to
      substrate (VS-based) ratio ranged from 4.06 to 4.47. Although methanogenesis
      proceeded fairly well the hydrolysis seemed to be the rate limiting step. It is
      possible start up psychrophilic dry anaerobic digestion of cow feces and wheat
      straw at feed TS of 35 % within 7-10 successive cycles (147-210 days). 

PMID- 26289774
TI  - Mating patterns of female Leon Springs pupfish Cyprinodon bovinus.
AB  - In a field study of Leon Springs pupfish Cyprinodon bovinus, two questions about
      female promiscuity were investigated. First, were females selective in the males
      with whom they spawned or were they unselective, spawning randomly among males?
      Second, how promiscuous were the females, i.e. with how many males did they
      spawn? If simply spawning with many males maximized a female's reproductive
      success, then females might be expected to spawn randomly with as many males as
      possible. Alternatively, if females were selective but engaged in multiple
      mating, they would limit their spawning to preferred males. In the only wild
      population of this endangered fish, breeding males defend closely associated
      territories in the shallow margins of a single desert pool. No territories were
      observed elsewhere in the pool. Therefore, all territorial males were present
      simultaneously and females could survey all of them, depositing any number of
      eggs with one, a few or many males. Rather than spawning randomly, females
      surveyed many males first, visited relatively few males and ultimately spawned
      with a small fraction of those available males. With increasing numbers of
      spawns, however, females increased the number of different mates with whom they
      spawned. Thus, females showed a bet-hedging tactic of having a narrow mate
      preference while also laying eggs in the territories of other males, possibly to
      reduce egg predation and to avoid inbreeding.

PMID- 26289775
TI  - 1H, 13C and 15N resonance assignments and second structure information of Fag s
      1: Fagales allergen from Fagus sylvatica.
AB  - Fagales allergens belonging to the Bet v 1 family account responsible for the
      majority of spring pollinosis in the temperate climate zones in the Northern
      hemisphere. Among them, Fag s 1 from beech pollen is an important trigger of
      Fagales pollen associated allergic reactions. The protein shares high similarity
      with birch pollen Bet v 1, the best-characterized member of this allergen family.
      Of note, recent work on Bet v 1 and its homologues found in Fagales pollen
      demonstrated that not all allergenic members of this family have the capacity to
      induce allergic sensitization. Fag s 1 was shown to bind pre-existing IgE
      antibodies most likely primarily directed against other members of this multi
      allergen family. Therefore, it is especially interesting to compare the
      structures of Bet v 1-like pollen allergens, which have the potential to induce
      allergic sensitization with allergens that are mainly cross-reactive. This in the
      end will help to identify allergy eliciting molecular pattern on Bet v 1-like
      allergens. In this work, we report the (1)H, (15)N and (13)C NMR assignment of
      beech pollen Fag s 1 as well as the secondary structure information based on
      backbone chemical shifts.

PMID- 26289772
TI  - The role of germline mutations in the BRCA1/2 and mismatch repair genes in men
      ascertained for early-onset and/or familial prostate cancer.
AB  - Prostate cancer (PrCa) is one of the most common cancers diagnosed worldwide and
      5-10 % of all cases are estimated to be associated with inherited predisposition.
      Even though there is strong evidence that the genetic component is significant in
      PrCa, the genetic etiology of familial and early-onset disease is largely
      unknown. Although it has been suggested that men from families with hereditary
      breast/ovarian cancer (HBOC) and, more recently, with Lynch syndrome may have an
      increased risk for PrCa, the contribution of these syndromes to PrCa
      predisposition in families ascertained for early-onset and/or familial PrCa,
      independently of the presence of other cancers in the family, is uncertain. To
      quantify the contribution of genes associated with HBOC and Lynch syndromes to
      PrCa predisposition, we have tested for germline mutations 460 early-onset and/or
      familial PrCa patients. All patients were screened for the six mutations that are
      particularly common in Portugal and 38 of them were selected for complete
      sequencing of BRCA1/2 and/or MLH1, MSH2 and MSH6. Two patients were found to
      harbor the same MSH2 mutation and a third patient carried a Portuguese BRCA2
      founder mutation. None of the alterations were identified in 288 control
      subjects. Furthermore, we reviewed the 62 PrCa diagnoses in all HBOC (n = 161)
      and Lynch syndrome (n = 124) families previously diagnosed at our department, and
      found five other BRCA2 mutation carriers and two additional MSH2 mutation
      carriers. The clinicopathological characteristics of mutation carriers are in
      concordance with earlier data suggesting an aggressive PrCa phenotype and support
      the hypothesis that mutation carriers might benefit from targeted screening
      according to the gene mutated in the germline.

PMID- 26289777
TI  - Teens who use e-cigarettes are more likely to take up smoking, US study finds.

PMID- 26289776
TI  - Humanized microbiota mice as a model of recurrent Clostridium difficile disease.
AB  - BACKGROUND: Clostridium difficile disease is the leading antibiotic-associated
      cause of diarrhea and nosocomial acquired infection in the western world. The per
      annum burden in the USA alone amounts to 250,000 cases with 14,000 ascribed
      deaths and medical costs in excess of a billion dollars. Novel models for the
      study of C. difficile infection are therefore pertinent. RESULTS: Germ free
      C57BL/6 mice gavaged with a healthy human fecal microbiota maintained a stable
      "humanized" microbiota over multiple generations when housed under specific
      pathogen-free (SPF) conditions. As with mice containing a conventional
      microbiota, treatment with a five-antibiotic cocktail followed by a single dose
      of clindamycin renders the animals susceptible to C. difficile infection (CDI).
      Interestingly, after recovery from the initial CDI infection, a single
      intraperitoneal injection of clindamycin is sufficient to induce CDI relapse.
      Relapse of CDI can be induced up to 35 days postinfection after recovery from the
      initial infection, and multiple episodes of relapse can be induced. CONCLUSIONS:
      This model enables the study of recurrent C. difficile disease in a host
      containing a human-derived microbiota. Probiotic treatments using human-derived
      microbes, either prophylactic or curative, can be tested within the model. The
      identification and testing of human-derived microbial communities within a
      humanized microbiota mouse model may enable a higher rate of successful transfer
      of bacteria-based treatments from the lab to human patients due to the microbes
      involved initiating from, and being adapted to, the human GI tract.

PMID- 26289778
TI  - Elucidating the Structure of Chiral Molecules by using Amplified Vibrational
      Circular Dichroism: From Theory to Experimental Realization.
AB  - Recent experimental observations of enhanced vibrational circular dichroism (VCD)
      in molecular systems with low-lying electronically excited states suggest
      interesting new applications of VCD spectroscopy. The theory describing VCD
      enhancement through vibronic coupling schemes was derived by Nafie in 1983, but
      only recently experimental evidence of VCD amplification has demonstrated the
      extent to which this effect can be exploited as a structure elucidation tool to
      probe local structure. In this Concept paper, we give an overview of the physics
      behind vibrational circular dichroism, in particular the equations governing the
      VCD amplification effect, and review the latest experimental developments with a
      prospective view on the application of amplified VCD to locally probe
      biomolecular structure. 

PMID- 26289779
TI  - Halogen bonding-enhanced electrochemical halide anion sensing by redox-active
      ferrocene receptors.
AB  - The first examples of halogen bonding redox-active ferrocene receptors and their
      anion electrochemical sensing properties are reported. Halogen bonding was found
      to significantly amplify the magnitude of the receptor's metallocene redox
      couple's voltammetric responses for halide sensing compared to their hydrogen
      bonding analogues in both acetonitrile and aqueous-acetonitrile solvent media. 

PMID- 26289780
TI  - Sensitivity and specificity of General Movements Assessment for diagnostic
      accuracy of detecting cerebral palsy early in an Australian context.
AB  - AIM: The aim of this study was to calculate the sensitivity and specificity of
      the General Movements Assessment (GMA) for estimating diagnostic accuracy in
      detecting cerebral palsy (CP) in an Australian context by a newly established NSW
      rater network. METHODS: A prospective longitudinal cross-sectional study was
      conducted. The GMA was blind-rated from conventional video by two independent
      certified raters, blinded to medical history. A third rater resolved
      disagreements. High-risk population screening for CP using the GMA during the
      fidgety period (12-20 weeks) was carried out in four neonatal intensive care
      units and one CP service over a 30-month period (2012-2013). Participants were
      259 high-risk infants. Sensitivity and specificity values were calculated with
      true positives defined as a confirmed diagnosis of CP from a medical doctor.
      RESULTS: Of the 259 infants assessed, 1-year follow-up data were available for
      187. Of these, n = 48 had absent fidgety (high risk for CP), n = 138 had normal
      fidgety (low risk for CP), and n = 1 had abnormal fidgety (high risk for a
      neurological disorder). Of the 48 with absent fidgety movements, 39 had received
      a diagnosis of CP by 18 months and another 6 had an abnormal outcome. Of the n =
      138 normal fidgety cases, n = 99 cases had a normal outcome, n = 38 had an
      abnormal outcome but not CP, and n = 1 had CP. For detecting CP, we had a
      sensitivity of 98% and specificity of 94%. CONCLUSION: GMA was feasible in an
      Australian context and accurately identified CP with a sensitivity and
      specificity comparable with European standards and published neuroimaging data.

PMID- 26289781
TI  - Depression in hypertension and blood pressure variability over shorter time
      periods.

PMID- 26289782
TI  - Combined effects of hypertension and heart rate on the risk of stroke and
      coronary heart disease: a population-based prospective cohort study among Inner
      Mongolians in China.
AB  - The purpose of this study was to prospectively evaluate the combined effects of
      hypertension and heart rate on the risk of stroke and coronary heart disease
      (CHD) among Inner Mongolians. Based a cross-sectional survey in 2002-2003, a
      prospective cohort study was conducted among 2530 Mongolian people. We
      categorized the participants into four subgroups according to blood pressure and
      heart rate. Cox proportional hazards models and receiver operating characteristic
      (ROC) curves were used to evaluate the association between hypertension, heart
      rate, and stroke and CHD incidence. During the follow-up period, a total of 120
      stroke and 75 CHD patients were observed. Compared with normotensives with a
      heart rate <80 b.p.m., in a multivariate-adjusted model, the hazard ratios (HRs;
      95% confidence intervals (CIs)) of stroke for hypertensives with a heart rate <80
      b.p.m. and hypertensives with heart rate ?80 b.p.m. were 3.21 (1.80-5.70) and
      3.59 (1.95-6.62), respectively (all P<0.05); the HRs (95% CI) of CHD for
      hypertensives with a heart rate <80 b.p.m. and hypertensives with a heart rate
      ?80 b.p.m. were 2.09 (1.07-4.07) and 2.76 (1.43-5.36), respectively (all P<0.05).
      For both stroke and CHD incidence, the area under ROC curve for a model
      containing hypertension and a heart rate ?80 b.p.m. along with other conventional
      factors was significantly larger than the one containing only other conventional
      factors (all P<0.05). Hypertensives with a high heart rate had the highest risk
      of stroke and CHD among the Inner Mongolians. These results indicate that the
      coexistence of hypertension and high heart rate may be a valuable predictor of
      stroke and CHD incidence. 

PMID- 26289783
TI  - In silico mechanistic analysis of IRF3 inactivation and high-risk HPV E6 species
      dependent drug response.
AB  - The high-risk human papillomavirus E6 (hrHPV E6) protein has been widely studied
      due to its implication in cervical cancer. In response to viral threat, activated
      kinases phosphorylate the IRF3 autoinhibitory domain, inducing type1 interferon
      production. HPV circumvents the antiviral response through the possible E6
      interaction with IRF3 and abrogates p53's apoptotic activity by recruiting E6
      associated protein. However, the molecular mechanism of IRF3 inactivation by
      hrHPV E6 has not yet been delineated. Therefore, we explored this mechanism
      through in silico examination of protein-protein and protein-ligand docking,
      binding energy differences, and computational alanine mutagenesis. Our results
      suggested that the LxxLL motifs of IRF3 binds within the hydrophobic pocket of
      E6, precluding Ser-patch phosphorylation, necessary for IRF3 activation and
      interferon induction. This model was further supported by molecular dynamics
      simulation. Furthermore, protein-ligand docking and drug resistance modeling
      revealed that the polar patches in the pocket of E6, which are crucial for
      complex stability and ligand binding, are inconsistent among hrHPV species. Such
      variabilities pose a risk of treatment failure owing to point mutations that
      might render drugs ineffective, and allude to multi-drug therapy. Overall, this
      study reveals a novel perspective of innate immune suppression in HPV infections
      and suggests a plausible therapeutic intervention. 

PMID- 26289784
TI  - Biogeography of Nocardiopsis strains from hypersaline environments of Yunnan and
      Xinjiang Provinces, western China.
AB  - The genus Nocardiopsis is a widespread group within the phylum Actinobacteria and
      has been isolated from various salty environments worldwide. However, little is
      known about whether biogeography affects Nocardiopsis distribution in various
      hypersaline environments. Such information is essential for understanding the
      ecology of Nocardiopsis. Here we analyzed 16S rRNA, gyrB, rpoB and sodA genes of
      78 Nocardiopsis strains isolated from hypersaline environments in Yunnan and
      Xinjiang Provinces of western China. The obtained Nocardiopsis strains were
      classified into five operational taxonomic units, each comprising location
      specific phylo- and genotypes. Statistical analyses showed that spatial distance
      and environmental factors substantially influenced Nocardiopsis distribution in
      hypersaline environments: the former had stronger influence at large spatial
      scales, whereas the latter was more influential at small spatial scales. 

PMID- 26289785
TI  - Water Processable Polythiophene Nanowires by Photo-Cross-Linking and Click
      Functionalization.
AB  - Replacing or minimizing the use of halogenated organic solvents in the processing
      and manufacturing of conjugated polymer-based organic electronics has emerged as
      an important issue due to concerns regarding toxicity, environmental impact, and
      high cost. To date, however, the processing of well-ordered conjugated polymer
      nanostructures has been difficult to achieve using environmentally benign
      solvents. In this work, we report the development of water and alcohol
      processable nanowires (NWs) with well-defined crystalline nanostructure based on
      the solution assembly of azide functionalized poly(3-hexylthiophene) (P3HT-azide)
      and subsequent photo-cross-linking and functionalization of these NWs. The
      solution-assembled P3HT-azide NWs were successfully cross-linked by exposure to
      UV light, yielding good thermal and chemical stability. Residual azide units on
      the photo-cross-linked NWs were then functionalized with alkyne terminated
      polyethylene glycol (PEG-alkyne) using copper catalyzed azide-alkyne
      cycloaddition chemistry. PEG functionalization of the cross-linked P3HT-azide NWs
      allowed for stable dispersion in alcohols and water, while maintaining well
      ordered NW structures with electronic properties suitable for the fabrication of
      organic field effect transistors (OFETs). 

PMID- 26289786
TI  - Acute Gastric Rupture in a Giant Inguinoscrotal Hernia.
AB  - Inguinoscrotal gastric herniation is a rare occurrence and generally presents
      with obstruction when encountered. We present a case of acute spontaneous gastric
      rupture in a giant inguinoscrotal hernia which was managed surgically in a one
      stage procedure with primary gastric and hernia repair. A subtotal colectomy was
      performed due to risk of volvulus as well as allowing for primary closure of the
      abdominal wall. This case illustrates the possibilities in terms of hernia size
      and contents, in addition to the potential complications that may ensue.
      Moreover, this case illustrates that adherence to the principles of hernia repair
      can equip the surgeon to deal with rare and unfamiliar presentations.

PMID- 26289787
TI  - Early investigational drugs targeting tau protein for the treatment of
      Alzheimer's disease.
AB  - INTRODUCTION: Alzheimer's disease (AD) is a progressive neurodegenerative
      disorder that is a significant burden to society. With continual expansion of our
      understanding of the disease, novel therapies are emerging as potential
      therapeutics to either halt or reverse progression of the disease. AREAS COVERED:
      This paper aims to provide an overview of current drug therapies aimed at
      targeting the tau protein. With this protein known to be a noted pathologic
      finding of the disease, trials of therapeutics aimed at this protein have been
      under investigation. This article is based on data obtained from PubMed searches,
      TauRx, ALZFORUM, and Clinicaltrials.gov with search terms including: anti-tau,
      tau therapeutic agents in AD, Phase 0, I, II, III trials in AD, monoclonal
      antibodies and vaccines. EXPERT OPINION: Broad-based treatments that target tau,
      including microtubule stabilization and tau aggregation inhibitors, appear to be
      of greatest promise. Immunotherapy appears to be relatively safe and efficacious
      but narrow whereas protein kinase inhibition has not demonstrated clinical
      benefit to date.

PMID- 26289788
TI  - An overview of developing TNF-alpha targeted therapy for the treatment of
      psoriasis.
AB  - INTRODUCTION: Three biologic drugs targeting TNF-alpha are approved to treat
      moderate-to-severe cutaneous psoriasis. These are adalimumab, etanercept and
      infliximab. These drugs are given by subcutaneous injection or intravenous
      infusion, and while generally safe and effective, they are expensive with
      potential for side effects. Thus, numerous new drug candidates are under
      development that also target TNF-alpha. AREAS COVERED: In this review, the
      authors detail several drugs under development that target TNF-alpha, focusing on
      those drugs in preclinical, Phase I and II trials. The authors describe emerging
      biologic psoriasis therapies, including biosimilars and novel biologics, in
      addition to several synthetic and naturally derived small-molecule drug
      candidates. EXPERT OPINION: The currently approved TNF-alpha antagonists benefit
      from over 10 years of safety and efficacy data. The expense and method of
      administration of these biologics, however, can be cumbersome, and less expensive
      alternatives have the potential to benefit patients with psoriasis. It is
      inevitable, despite the introduction of new anti-IL-17 therapies, that
      established TNF-alpha targeted therapies, as well as newcomers targeting TNF
      alpha, will continue to play an important role in the lifelong management of
      psoriasis.

PMID- 26289789
TI  - Investigational hormone receptor agonists as ongoing female contraception: a
      focus on selective progesterone receptor modulators in early clinical
      development.
AB  - INTRODUCTION: As efforts are made to continue to increase the safety of
      contraceptive methods, those without estrogen have attracted new attention.
      Progestin-only options are available in many delivery systems, but most cause
      disturbed bleeding patterns. For gynecologic patients, selective progesterone
      receptor modulators (SPRMs) have been approved for medical abortion, for
      ovulation suppression in emergency contraception, and for the treatment of heavy
      menstrual bleeding due to leiomyoma. AREAS COVERED: This article discusses the
      role of SPRMs in controlling fertility on an ongoing basis with particular
      emphasis on mifepristone and ulipristal acetate (UPA), since none of the other
      compounds has progressed out of early Phase I - II testing. It also discusses
      important information about the mechanisms of action and safety of these two
      SPRMs. EXPERT OPINION: Of all the investigational hormone agonist/antagonists,
      SPRMs have demonstrated the greatest potential as ongoing female contraceptives.
      They have the ability to suppress ovulation after initiation of the luteinizing
      hormone (LH) surge without affecting ovarian production of estrogen or inducing
      any significant metabolic changes. SPRMs may well be able to provide longer term
      contraception as oral agents, vaginal rings, and perhaps even intrauterine
      devices. UPA has the greatest promise. Current research needs to be expanded.

PMID- 26289790
TI  - Targeted therapy and promising novel agents for the treatment of advanced soft
      tissue sarcomas.
AB  - INTRODUCTION: Soft tissue sarcomas (STS) are a rare and difficult to treat
      malignancy. Efforts to utilize targeted therapy have been ongoing for the last
      decade and have resulted in the approval of pazopanib for treatment of advanced
      disease. Although several other agents have been investigated, the inability to
      predict responses remains a limiting factor to the incorporation of these agents
      into treatment. AREAS COVERED: The authors summarize recent clinical findings
      from studies focused on targeted agents in STS. The authors also discuss the
      potential approaches and ongoing clinical trials with novel agents. EXPERT
      OPINION: A major challenge in the treatment of advanced STS remains a lack of
      predictive biomarkers to guide therapy and the heterogeneity of response among
      different histologies of sarcoma. Incorporation of predictive biomarker analysis
      into clinical trials is warranted. Additionally, mechanisms of treatment
      resistance and parallel pathways of tumor growth pose challenges in how we treat
      these tumors. An active area of research in STS is the use of novel combinations
      of agents, such as chemotherapy combined with multi-targeted agents. The
      potential of immune check point inhibitors is being explored in advanced STS and
      is hoped to further expand our treatment armamentarium.

PMID- 26289791
TI  - Novel chemotherapeutics and other therapies for treating high-grade glioma.
AB  - INTRODUCTION: Despite extensive research, high-grade glioma (HGG) remains a dire
      diagnosis with no change in the standard of care in almost a decade. However,
      recent advancements uncovering molecular biomarkers of brain tumors and tumor
      specific antigens targeted by immunotherapies provide opportunities for novel
      personalized treatment regimens to improve survival. AREAS COVERED: In this
      review, the authors provide a comprehensive overview of recent therapeutic
      advancements in HGG. Furthermore, they describe new molecular biomarkers and
      molecular classifications, in addition to updated research on bevacizumab,
      targeted molecular therapies, immunotherapy and alternative delivery methods that
      overcome the blood-brain barrier to reach the target tumor tissue. Challenges
      regarding each therapy are also outlined. The authors also provide some insight
      into a novel non-chemotherapeutic treatment for malignant glioma, NovoTTFA, as
      well as a summary of current treatment options for recurrence. EXPERT OPINION:
      Current research for treating malignant gliomas are paving the path to
      personalized therapy, including immunotherapy, that involve integrated genomic
      and histolopathologic data, as well as a multi-modal treatment regimen.
      Immunotherapy will potentially be the next addition to the current standard of
      care, specialized to the antigens presented on the tumors. The results of the
      current trials of multi-antigen vaccines are eagerly anticipated.

PMID- 26289792
TI  - Substance use and related problems among U.S. women who identify as mostly
      heterosexual.
AB  - BACKGROUND: We used data from a nationally representative sample to compare
      substance use outcomes among adult women who identified as mostly heterosexual
      with those who identified as exclusively (only) heterosexual. METHOD: We analyzed
      data from mostly heterosexual women and only heterosexual women in Wave 5 (2001)
      of the National Study of Health and Life Experiences of Women (weighted n =
      1085). RESULTS: Mostly heterosexual women were significantly more likely than
      only heterosexual women to report every alcohol-related outcome included in our
      analyses except lifetime treatment. Odds of lifetime and past-year marijuana and
      cocaine use showed larger differences, with mostly heterosexual women nearly four
      times as likely as only heterosexual women to report lifetime cocaine use and
      five times as likely to report past-year use. CONCLUSIONS: We recommend that
      researchers use measures of sexual identity that include more nuanced response
      options, and that health care providers learn about the existence, large numbers,
      and risk/protective factors associated with substance use patterns of mostly
      heterosexual women.

PMID- 26289793
TI  - Characterization of hepatic lipid profiles in a mouse model with nonalcoholic
      steatohepatitis and subsequent fibrosis.
AB  - Nonalcoholic steatohepatitis (NASH) is a major health problem since it often
      leads to hepatocellular carcinoma. However, the underlying mechanisms of NASH
      development and subsequent fibrosis have yet to be clarified. We compared
      comprehensive lipidomic profiles between mice with high fat diet (HFD)-induced
      steatosis and STAM mice with NASH and subsequent fibrosis. The STAM mouse is a
      model that demonstrates NASH progression resembling the disease in humans: STAM
      mice manifest NASH at 8 weeks, which progresses to fibrosis at 12 weeks, and
      finally develop hepatocellular carcinoma. Overall, 250 lipid molecules were
      detected in the liver using liquid chromatography-mass spectrometry. We found
      that STAM mice with NASH presented a significantly higher abundance of
      sphingolipids and lower levels of triacylglycerols than the HFD-fed control mice.
      The abundance of certain fatty acids in phospholipid side chains was also
      significantly different between STAM and control mice, although global levels of
      phosphatidylcholines and phosphatidylethanolamines were comparable. Finally,
      increase in levels of acylcarnitines and some diacylglycerols was observed in
      STAM mice toward the fibrosis stage, but not in age-matched control mice. Our
      study provides insights into the lipid status of the steatotic, NASH, and
      fibrotic liver that would help elucidate the molecular pathophysiology of NASH
      progression. 

PMID- 26289795
TI  - Compact DD generator-based neutron activation analysis (NAA) system to determine
      fluorine in human bone in vivo: a feasibility study.
AB  - The subject of whether fluorine (F) is detrimental to human health has been
      controversial for many years. Much of the discussion focuses on the known
      benefits and detriments to dental care and problems that F causes in bone
      structure at high doses. It is therefore advantageous to have the means to
      monitor F concentrations in the human body as a method to directly assess
      exposure. F accumulates in the skeleton making bone a useful biomarker to assess
      long term cumulative exposure to F. This study presents work in the development
      of a non-invasive method for the monitoring of F in human bone. The work was
      based on the technique of in vivo neutron activation analysis (IVNAA). A compact
      deuterium-deuterium (DD) generator was used to produce neutrons. A
      moderator/reflector/shielding assembly was designed and built for human hand
      irradiation. The gamma rays emitted through the (19)F(n,gamma)(20)F reaction were
      measured using a HPGe detector. This study was undertaken to (i) find the
      feasibility of using DD system to determine F in human bone, (ii) estimate the F
      minimum detection limit (MDL), and (iii) optimize the system using the Monte
      Carlo N-Particle eXtended (MCNPX) code in order to improve the MDL of the system.
      The F MDL was found to be 0.54 g experimentally with a neutron flux of 7   *  
      10(8) n s(-1) and an optimized irradiation, decay, and measurement time scheme.
      The numbers of F counts from the experiment were found to be close to the (MCNPX)
      simulation results with the same irradiation and detection parameters. The
      equivalent dose to the irradiated hand and the effective dose to the whole body
      were found to be 0.9 mSv and 0.33 MUSv, respectively. Based on these results, it
      is feasible to develop a compact DD generator based IVNAA system to measure bone
      F in a population with moderate to high F exposure.

PMID- 26289794
TI  - Ten influenza seasons in France: distribution and timing of influenza A and B
      circulation, 2003-2013.
AB  - BACKGROUND: Describing the circulation of influenza viruses and the
      characteristics of seasonal epidemics remains an essential tool to optimize the
      strategies of influenza prevention and control. Special attention has been
      recently paid to influenza B in the context of the availability of a quadrivalent
      vaccine, containing two influenza B strains. METHODS: We used data from a
      practitioners-based influenza surveillance network to describe the circulation of
      influenza viruses in France from 2003-2004 to 2012-2013. Nasopharyngeal swabs
      taken from acute respiratory infection (ARI) patients between October and April
      were tested for influenza. We reported the number of influenza cases by virus
      type (A, B), subtype (A(H1), A(H3)) and B lineage (Yamagata, Victoria) in each
      season and determined the frequency of influenza B vaccine mismatch. We estimated
      weekly incidence of influenza by extrapolating reported influenza cases to the
      French population. We compared the temporal characteristics of the epidemics
      caused by influenza A(H1), A(H3) and B. RESULTS: Overall, 49,919 ARI patients
      were tested, of which 16,287 (32.6 %) were positive for influenza. Type B virus
      caused 23.7 % of all influenza cases. Virus subtypes A(H1) and A(H3) caused 51.6
      % and 48.4 % of influenza A cases, respectively. Viruses of the B-Yamagata and B
      Victoria lineage caused 62.8 % and 37.2 % of influenza B cases, respectively.
      There was an influenza B vaccine mismatch in three of the five seasons where
      influenza B caused 10 % or more of all influenza cases. Influenza A(H3) had the
      highest average value of estimated weekly incidence during the study period.
      Influenza B peaked an average 3.8 weeks later than influenza A when both virus
      types were circulating. No differences in the duration of influenza A and B
      epidemics were observed. CONCLUSIONS: Influenza A(H3) was the most prevalent
      influenza type during the study period. Influenza B caused around one fourth of
      all influenza cases and tended to circulate later than influenza A. The frequency
      of influenza B vaccine mismatches was substantial. Timely data on the circulation
      of influenza viruses collected within influenza surveillance systems are
      essential to optimize influenza prevention and control strategies.

PMID- 26289796
TI  - Reasons for declining extended information visit on prenatal screening among
      pregnant women and their partners.
AB  - OBJECTIVE: A two-step model on information on prenatal screening consists of
      brief information at the first visit at the Maternal Health Care Centre and an
      offer of extended information at a separate visit. There is a lack of knowledge
      why some pregnant women and their partners refrain from the extended information
      visit. The aim of this study was to explore their reasons. METHOD: Eight
      qualitative interviews were analyzed using Interpretive Description. RESULTS: In
      the first theme 'From an individual view', the interviewees saw the invitation
      from their own points of view. They refrained because they did not want to
      receive any more information or had taken an individual position against
      chromosomal testing. In the theme, 'From a societal view', the interviewees
      perceived the offer as part of a societal view on prenatal screening that they
      could not support. CONCLUSION: The findings show that these interviewees' reasons
      of declining an extended information visit are multidimensional and influenced by
      different views, from both an individual perspective and a more societal one.
      Health care professionals should be aware that some persons could have a
      different view on health care services and could be reluctant to accept offered
      services.

PMID- 26289797
TI  - Genesis of Azole Antifungal Resistance from Agriculture to Clinical Settings.
AB  - Azole fungal resistance is becoming a major public health problem in medicine in
      recent years. However, it was known in agriculture since several decades; the
      extensive use of these compounds results in contamination of air, plants, and
      soil. The increasing frequency of life-threatening fungal infections and the
      increase of prophylactical use of azoles in high-risk patients, taken together
      with the evolutionary biology evidence that drug selection pressure is an
      important factor for the emergence and spread of drug resistance, can result in a
      dramatic scenario. This study reviews the azole use in agricultural and medical
      contexts and discusses the hypothetical link between its extensive use and the
      emergence of azole resistance among human fungal pathogens. 

PMID- 26289798
TI  - Effect of acute exercise-induced fatigue on maximal rate of heart rate increase
      during submaximal cycling.
AB  - Different mathematical models were used to evaluate if the maximal rate of heart
      rate (HR) increase (rHRI) was related to reductions in exercise performance
      resulting from acute fatigue. Fourteen triathletes completed testing before and
      after a 2-h run. rHRI was assessed during 5 min of 100-W cycling and a sigmoidal
      (rHRIsig) and exponential (rHRIexp) model were applied. Exercise performance was
      assessed using a 5-min cycling time-trial. The run elicited reductions in time
      trial performance (1.34 +/- 0.19 to 1.25 +/- 0.18 kJ . kg(-1), P < 0.001),
      rHRIsig (2.25 +/- 1.0 to 1.14 +/- 0.7 beats . min(-1) . s(-1), P < 0.001) and
      rHRIexp (3.79 +/- 2.07 to 1.98 +/- 1.05 beats . min(-1) . s(-1), P = 0.001), and
      increased pre-exercise HR (73.0 +/- 8.4 to 90.5 +/- 11.4 beats . min(-1), P <
      0.001). Pre-post run difference in time-trial performance was related to
      difference in rHRIsig (r = 0.58, P = 0.04 and r = 0.75, P = 0.003) but not
      rHRIexp (r = -0.04, P = 0.9 and r = 0.27, P = 0.4) when controlling for
      differences in pre-exercise and steady-state HR. rHRIsig was reduced following
      acute exercise-induced fatigue, and correlated with difference in performance.

PMID- 26289799
TI  - Endoplasmic reticulum stress in brain ischemia.
AB  - Endoplasmic reticulum (ER) stress is an intricate mechanism that mediates
      numerous responses during brain ischemia, thus being essential to determine the
      fate of neurons. In recent years, studies of the mechanisms of brain ischemic
      injury have centered on ER stress, glutamate excitotoxicity, dysfunction of
      mitochondria, inflammatory reactions, calcium overload and death receptor
      pathways. The role of ER stress is highly important. In addition to resulting in
      neuronal cell death through calcium toxicity and apoptotic pathways, ER stress
      also triggers a series of adaptive responses including unfolded protein response
      (UPR), autophagy, the expression of pro-survival proteins and the enhancement of
      ER self-repair ability, leading to less ischemic brain damage. This paper
      provides an overview of recent advances in understanding of the relations between
      ER stress and brain ischemia. 

PMID- 26289800
TI  - Short linear motif acquisition, exon formation and alternative splicing determine
      a pathway to diversity for NCoR-family co-repressors.
AB  - Vertebrate NCoR-family co-repressors play central roles in the timing of embryo
      and stem cell differentiation by repressing the activity of a range of
      transcription factors. They interact with nuclear receptors using short linear
      motifs (SLiMs) termed co-repressor for nuclear receptor (CoRNR) boxes. Here, we
      identify the pathway leading to increasing co-repressor diversity across the
      deuterostomes. The final complement of CoRNR boxes arose in an ancestral
      cephalochordate, and was encoded in one large exon; the urochordates and
      vertebrates then split this region between 10 and 12 exons. In Xenopus,
      alternative splicing is prevalent in NCoR2, but absent in NCoR1. We show for one
      NCoR1 exon that alternative splicing can be recovered by a single point mutation,
      suggesting NCoR1 lost the capacity for alternative splicing. Analyses in Xenopus
      and zebrafish identify that cellular context, rather than gene sequence,
      predominantly determines species differences in alternative splicing. We identify
      a pathway to diversity for the NCoR family beginning with the addition of a SLiM,
      followed by gene duplication, the generation of alternatively spliced isoforms
      and their differential deployment. 

PMID- 26289801
TI  - Proper symmetric and asymmetric endoplasmic reticulum partitioning requires
      astral microtubules.
AB  - Mechanisms that regulate partitioning of the endoplasmic reticulum (ER) during
      cell division are largely unknown. Previous studies have mostly addressed ER
      partitioning in cultured cells, which may not recapitulate physiological
      processes that are critical in developing, intact tissues. We have addressed this
      by analysing ER partitioning in asymmetrically dividing stem cells, in which
      precise segregation of cellular components is essential for proper development
      and tissue architecture. We show that in Drosophila neural stem cells, called
      neuroblasts, the ER asymmetrically partitioned to centrosomes early in mitosis.
      This correlated closely with the asymmetric nucleation of astral microtubules
      (MTs) by centrosomes, suggesting that astral MT association may be required for
      ER partitioning by centrosomes. Consistent with this, the ER also associated with
      astral MTs in meiotic Drosophila spermatocytes and during syncytial embryonic
      divisions. Disruption of centrosomes in each of these cell types led to improper
      ER partitioning, demonstrating the critical role for centrosomes and associated
      astral MTs in this process. Importantly, we show that the ER also associated with
      astral MTs in cultured human cells, suggesting that this centrosome/astral MT
      based partitioning mechanism is conserved across animal species. 

PMID- 26289802
TI  - Tricarbonyl (99m)Tc(i) and Re(i)-thiosemicarbazone complexes: synthesis,
      characterization and biological evaluation for targeting bacterial infection.
AB  - Methyl, ethyl and phenyl nitrofuryl thiosemicarbazone ligands (, and
      respectively) were radiolabeled with freshly prepared aqueous solution of a
      fac[(99m)Tc(CO)3(H2O)3](+) precursor. The radiochemical yield was around 98% as
      determined by thin layer chromatography and HPLC. The complexes exhibited
      substantial stability. The corresponding Re(i) complexes were prepared from a
      Re(CO)5Br precursor to understand the coordination behavior of the ligands
      against a tricarbonyl rhenium(i) precursor. The rhenium(i) complexes were
      characterized by means of IR, NMR and mass spectroscopic studies as well as by X
      ray crystallography, and correlated with the technetium complexes by means of
      HPLC studies. Electrochemical reduction of monomeric Re(CO)3-complexes of
      nitrofuryl ethyl thiosemicarbazone was also studied using cyclic voltammetry.
      Biodistribution studies of (99m)Tc(CO)3-labeled thiosemicarbazones in rats
      intramuscularly infected with S. aureus exhibited substantial in vivo stability
      of the complex and moderate accumulation at the site of focal infection. 

PMID- 26289803
TI  - [Pulmonary Langerhans cell histiocytosis].
AB  - Pulmonary Langerhans cell histiocytosis is regarded as a reactive proliferation
      of the dendritic Langerhans cell population stimulated by chronic tobacco-derived
      plant proteins due to incomplete combustion but can also occur in childhood as a
      tumor-like systemic disease. Currently, both these forms cannot be
      morphologically distinguished. In the lungs a nodular proliferation of Langerhans
      cells occurs in the bronchial mucosa and also peripherally in the alveolar septa
      with an accompanying infiltration by eosinophilic granulocytes and destruction of
      the bronchial wall. Langerhans cells can be selectively detected with antibodies
      against CD1a and langerin. In the reactive isolated pulmonary form, abstinence
      from tobacco smoking in most patients leads to regression of infiltration and
      improvement of symptoms. In high-resolution computed tomography (HRCT) the small
      star-like scars can still be detected even after complete cessation of tobacco
      smoking.

PMID- 26289804
TI  - [Histiocytic disorders].

PMID- 26289806
TI  - Processes of Care in Breast Reconstruction and the Long-Term Impact of a
      Comprehensive Breast Center.
AB  - BACKGROUND: Increased emphasis has been placed on process outcomes for breast
      cancer care, but limited data exists on these measures for breast reconstruction.
      These processes are likely to be impacted by increased centralization of care
      into comprehensive breast centers (CBC). Our study objectives were to define
      measures for processes of care in breast reconstruction and to determine the
      effect of a CBC on these measures. METHODS: A 5-year review was performed of
      patients who underwent mastectomy with or without reconstruction for a newly
      diagnosed breast cancer between 2010 and 2014, which spans from 1 year before to
      4 years after introduction of our CBC. RESULTS: A total of 4179 patients were
      reviewed. The referral rate for immediate reconstruction increased from 40.0 to
      70.8 % (p < .001), and the immediate reconstruction rate increased from 36.7 to
      65.0 % (p < .001), both plateauing in the fourth study year. The interval between
      surgical oncology and plastic surgery consultation decreased (from 9.2 to 2.5
      days; p < .001), and stabilized in the second study year. The interval between
      plastic surgery consultation and surgery decreased throughout the entire study
      period (from 37.6 to 20.8 days; p < .001), resulting in continued improvements in
      the interval between surgical oncology consultation and surgery (from 46.8 to
      23.3 days, p < .001). CONCLUSIONS: In breast reconstruction, a CBC results in
      improvements in process outcomes, some of which are realized in the short-term
      and others in the long-term. The timeliness of treatment of patients who undergo
      immediate postmastectomy reconstruction can be similar to targets set for
      patients who undergo mastectomy alone.

PMID- 26289805
TI  - Complement Inhibition: A Novel Form of Immunotherapy for Colon Cancer.
AB  - BACKGROUND: Complement is a central part of both the innate and adaptive immune
      response and its activation has traditionally been considered part of the
      immunosurveillance response against cancer. Its pro-inflammatory role and its
      contribution to the development of many illnesses associated with inflammatory
      states implicate complement in carcinogenesis. METHODS: We evaluated the role of
      three protein inhibitors of complement-cobra venom factor, humanized cobra venom
      factor, and recombinant staphylococcus aureus superantigen-like protein 7-in the
      setting of a transplantable murine colon cancer model. Outcomes were evaluated by
      monitoring tumor growth, and flow cytometry, ELISPOT, and quantitative real-time
      PCR were used to determine the impact of complement inhibition on the host immune
      response. RESULTS: Complement inhibitors were effective at depleting complement
      component C3 in tumor bearing mice and this was temporally correlated with a
      decreased rate of tumor growth during the establishment of tumors. Treatment with
      cobra venom factor resulted in increased CD8(+) T cells as a percentage of tumor
      infiltrating cells as well as a reduced immunosuppressive environment evidenced
      by decreased myeloid derived suppressor cells in splenocytes of treated mice.
      Complement inhibition resulted in increased expression of the chemoattractive
      cytokines CCL5, CXCL10, and CXCL11. DISCUSSION: Complement depletion represents a
      promising mode of immunotherapy in cancer by its ability to impair tumor growth
      by increasing the host's effective immune response to tumor and diminishing the
      immunosuppressive effect created by the tumor microenvironment and ultimately
      could be utilized as a component of combination immunotherapy.

PMID- 26289808
TI  - Conditional Survival After Cytoreductive Surgery with Heated Intraperitoneal
      Chemotherapy for Low- and High-Grade Appendiceal Primaries.
AB  - INTRODUCTION: Survival of patients after cytoreductive surgery (CRS) and heated
      intraperitoneal chemotherapy for appendiceal neoplasms is projected by
      conventional overall survival (OS) curves that do not address the survival time a
      patient has already accrued. We sought to study the conditional survival (CS)
      after CRS, contingent on patients surviving a fixed duration of time after
      surgery. METHODS: A retrospective analysis of 493 appendiceal cancer patients
      from a prospective database was performed. OS was calculated for patients who
      achieved a complete CRS. CS was estimated based on Kaplan-Meier curves to
      determine what the patient's long-term survival (3-, 5-, 7-, or 10-year) would be
      if they were alive at 1, 2, or 3 years from surgery. RESULTS: OS at 5 and 10
      years for 137 low-grade patients with complete resections was 83.3 and 74.2 %,
      respectively. For low-grade patients still alive at 3 years, 5- and 10-year CS
      was 93.4 and 83.2 %, respectively. For the 35 high-grade patients with complete
      CRS who survived to 3 years, CS at 10 years was 41.7 %, while their 10-year
      conventional OS was 24.6 %. CONCLUSIONS: Conventional analysis underestimates OS
      due to unpredictable variations in tumor biology. When adjusted for time already
      elapsed since surgery, improvements in survival estimates are more pronounced
      with high-grade tumors. CS outcomes can be used in determining the optimal
      frequency of long-term follow-up of these patients.

PMID- 26289807
TI  - The Prognostic Relevance of Subcarinal Lymph Node Dissection in Esophageal
      Squamous Cell Carcinoma.
AB  - BACKGROUND: The objective of this study was to evaluate the prognostic relevance
      of subcarinal lymph node dissection in patients with esophageal squamous cell
      carcinoma (ESCC) and to identify a subset of patients in whom subcarinal lymph
      node dissection can be omitted. METHODS: We retrospectively analyzed 342
      consecutive patients with thoracic ESCC who underwent R0 subtotal esophagectomy.
      All patients underwent subcarinal lymph node dissection. The efficacy index
      (frequency of metastasis to a particular lymph node station multiplied by the 5
      year disease-specific survival rate of patients with metastasis to the station)
      was calculated for the subcarinal lymph node station, and the prognostic impact
      of dissecting this station was estimated with reference to the main tumor
      location. Independent predictive factors for pathological subcarinal lymph node
      metastasis were analyzed using a proportional hazards model. RESULTS: The overall
      frequency of metastasis to the subcarinal lymph nodes was 7.0 % (2.4, 8.9, and
      5.8 % in patients with upper, middle, and lower thoracic ESCC, respectively). The
      efficacy index for the middle thoracic esophagus was 2.9, and that for the upper
      and lower thoracic esophagus was 0.0. The 5-year disease-free survival rate was
      significantly lower in patients with pathological subcarinal lymph node
      metastasis than those without (23.1 vs. 67.5 %, respectively; log-rank p <
      0.0001). In multivariate analysis, clinical T stage (T2-T4) was the independent
      predictive factor for pathological subcarinal lymph node metastasis (p = 0.021).
      CONCLUSIONS: Subcarinal lymph node dissection might have little value in patients
      with upper and lower thoracic ESCC and could be omitted, especially for
      superficial carcinoma.

PMID- 26289809
TI  - Multicenter Retrospective Study of Adjuvant Therapy for Patients with
      Pathologically Lymph Node-Positive Oral Squamous Cell Carcinoma: Analysis of
      Covariance Using Propensity Score.
AB  - BACKGROUND: The presence of pathologically positive lymph nodes (pN+) is a well
      known prognostic factor in oral squamous cell carcinoma (OSCC). The aims of this
      retrospective multicenter study were to assess the prognosis of OSCC patients
      with pN+ disease; to compare the prognosis of patients with pN+ disease who
      underwent surgery plus radiotherapy (RT) or concurrent chemoradiotherapy (CCRT)
      with that of patients who underwent surgery only; and to account for biases
      associated with treatment selection of adjuvant RT or CCRT. METHODS: The records
      of 313 OSCC patients with pN+ disease were retrospectively reviewed. The main
      outcome measures were 5-year disease-specific survival (DSS) and overall survival
      (OS) rates. To reduce selection biases associated with retrospective data, the
      treatment groups were evaluated by Cox proportional hazard analysis with
      propensity score as a covariate. RESULTS: The 5-year OS and DSS survival rates
      for the entire patient cohort were 51.8 and 59.2 %, respectively. T3-4 stage,
      closed (<5 mm) margin distance, >=4 involved nodes, and extracapsular spread were
      significant poor prognostic factors for OS and DSS. In the propensity score
      analysis, postoperative RT/CCRT significantly improved OS and DSS compared to
      surgery only. However, OS and DSS were not significantly different between
      patients who received postoperative RT and CCRT. CONCLUSION: The addition of
      cytotoxic chemotherapy to RT does not provide additional survival benefit in OSCC
      patients with pN+ disease. Alternative strategies, such as molecular targeted
      therapies, are needed to further improve the survival of high-risk OSCC patients
      with pN+ disease.

PMID- 26289810
TI  - Exercise training modifies walking kinematics and energy cost in obese
      adolescents: A pilot controlled trial.
AB  - The aim of this study was to investigate the effects of a weight loss
      intervention based on physical exercise on the relationship between energy cost
      and stride frequency during walking in obese teenagers. Participants aged 13-16
      years old were assigned to a training (n = 14) and control (n = 10) groups.
      During eight weeks, the training group performed three 60-min weekly sessions of
      high-intensity intermittent activities coupled with aerobic training. Body
      composition, gait parameters and energy cost during 4-min walking bouts at
      participants' most comfortable speed and preferred stride frequency (PSF), PSF
      10%, PSF + 10%, PSF-20% and PSF + 20% were measured before and after
      intervention. The effects of training and stride frequencies on the energy cost
      of walking were analysed by an ANOVA with repeated measures. The main results
      showed that the exercise intervention induced a significant increase in walking
      speed (+23.2%), and significant decreases in body mass (-1.4%), body fat
      percentage (-2.1%) and energy cost of walking at various frequencies (decreases
      ranging from -10.5% to -20.4%, p < .05). In addition, significantly greater
      decreases were shown at high frequencies (p < .05). No significant differences
      were shown in the control group (p > .05). These results suggest that this type
      of training is beneficial to reduce walking energy cost of obese teenagers, in
      particular at high frequencies. This should improve their well-being during daily
      activities.

PMID- 26289812
TI  - Modeling Population-Level Consequences of Polychlorinated Biphenyl Exposure in
      East Greenland Polar Bears.
AB  - Polychlorinated biphenyls (PCBs) can cause endocrine disruption, cancer,
      immunosuppression, or reproductive failure in animals. We used an individual
      based model to explore whether and how PCB-associated reproductive failure could
      affect the dynamics of a hypothetical polar bear (Ursus maritimus) population
      exposed to PCBs to the same degree as the East Greenland subpopulation. Dose
      response data from experimental studies on a surrogate species, the mink (Mustela
      vision), were used in the absence of similar data for polar bears. Two
      alternative types of reproductive failure in relation to maternal sum-PCB
      concentrations were considered: increased abortion rate and increased cub
      mortality. We found that the quantitative impact of PCB-induced reproductive
      failure on population growth rate depended largely on the actual type of
      reproductive failure involved. Critical potencies of the dose-response
      relationship for decreasing the population growth rate were established for both
      modeled types of reproductive failure. Comparing the model predictions of the age
      dependent trend of sum-PCBs concentrations in females with actual field
      measurements from East Greenland indicated that it was unlikely that PCB exposure
      caused a high incidence of abortions in the subpopulation. However, on the basis
      of this analysis, it could not be excluded that PCB exposure contributes to
      higher cub mortality. Our results highlight the necessity for further research on
      the possible influence of PCBs on polar bear reproduction regarding their
      physiological pathway. This includes determining the exact cause of reproductive
      failure, i.e., in utero exposure versus lactational exposure of offspring; the
      timing of offspring death; and establishing the most relevant reference metrics
      for the dose-response relationship.

PMID- 26289811
TI  - Dipeptide species regulate p38MAPK-Smad3 signalling to maintain chronic
      myelogenous leukaemia stem cells.
AB  - Understanding the specific survival of the rare chronic myelogenous leukaemia
      (CML) stem cell population could provide a target for therapeutics aimed at
      eradicating these cells. However, little is known about how survival signalling
      is regulated in CML stem cells. In this study, we survey global metabolic
      differences between murine normal haematopoietic stem cells (HSCs) and CML stem
      cells using metabolomics techniques. Strikingly, we show that CML stem cells
      accumulate significantly higher levels of certain dipeptide species than normal
      HSCs. Once internalized, these dipeptide species activate amino-acid signalling
      via a pathway involving p38MAPK and the stemness transcription factor Smad3,
      which promotes CML stem cell maintenance. Importantly, pharmacological inhibition
      of dipeptide uptake inhibits CML stem cell activity in vivo. Our results
      demonstrate that dipeptide species support CML stem cell maintenance by
      activating p38MAPK-Smad3 signalling in vivo, and thus point towards a potential
      therapeutic target for CML treatment. 

PMID- 26289813
TI  - Fast-Target Analysis and Hourly Variation of 60 Pharmaceuticals in Wastewater
      Using UPLC-High Resolution Mass Spectrometry.
AB  - A fast and sensitive monitoring method for trace pharmaceuticals in the
      environment is vital because many of these compounds are ubiquitous, persistent,
      and biologically active with recognized endocrine-disruption and pharmacological
      functions. A rapid and reliable ultra high-performance liquid chromatography
      combined with tandem mass spectrometry was developed in the present study to
      simultaneously identify, confirm, and quantify 60 target pharmaceuticals in
      wastewater samples. The method uses a sub-2 um particle column for separating
      target compounds, which were subsequently quantified with the mass spectrometer.
      Using this high-throughput analysis method, a single injection could provide
      results within 5 min for the pharmaceuticals. All of the target compounds were
      analyzed by the multiple-reaction monitoring with 15-ms fast polarity switching.
      Both intraday and interday precision analyses indicate excellent coefficient of
      variability. To evaluate the performance of the method, a standard solution (100
      and 1000 ng L(-1)) was spiked into complex wastewater samples. The tailing factor
      and peak width were also monitored and adjusted for optimizing peaks from the
      ultra high-performance liquid chromatograph. Of the target pharmaceuticals in
      wastewater of a sewage-treatment plant analyzed on an hourly basis, only 17
      compounds were detected, and others were lower than the method detection limits.
      Acetaminophen, cimetidine, and iopromide were all detected at >1 MUg L(-1), and
      their concentration profiles were similar to that of a nonsteroidal anti
      inflammatory drug detected in wastewater. Other noticeable pharmaceuticals were
      sulfamethoxazole and trimethoprim. Sources of pharmaceuticals in wastewater are
      briefly discussed. 

PMID- 26289814
TI  - Food Web Bioaccumulation Model for Resident Killer Whales from the Northeastern
      Pacific Ocean as a Tool for the Derivation of PBDE-Sediment Quality Guidelines.
AB  - Resident killer whale populations in the NE Pacific Ocean are at risk due to the
      accumulation of pollutants, including polybrominated diphenyl ethers (PBDEs). To
      assess the impact of PBDEs in water and sediments in killer whale critical
      habitat, we developed a food web bioaccumulation model. The model was designed to
      estimate PBDE concentrations in killer whales based on PBDE concentrations in
      sediments and the water column throughout a lifetime of exposure. Calculated and
      observed PBDE concentrations exceeded the only toxicity reference value available
      for PBDEs in marine mammals (1500 MUg/kg lipid) in southern resident killer
      whales but not in northern resident killer whales. Temporal trends (1993-2006)
      for PBDEs observed in southern resident killer whales showed a doubling time of
      ~5 years. If current sediment quality guidelines available in Canada for
      polychlorinated biphenyls are applied to PBDEs, it can be expected that PBDE
      concentrations in killer whales will exceed available toxicity reference values
      by a large margin. Model calculations suggest that a PBDE concentration in
      sediments of approximately 1.0 MUg/kg dw produces PBDE concentrations in resident
      killer whales that are below the current toxicity reference value for 95 % of the
      population, with this value serving as a precautionary benchmark for a management
      based approach to reducing PBDE health risks to killer whales. The food web
      bioaccumulation model may be a useful risk management tool in support of
      regulatory protection for killer whales.

PMID- 26289815
TI  - Detection of Anthropogenic Particles in Fish Stomachs: An Isolation Method
      Adapted to Identification by Raman Spectroscopy.
AB  - Microplastic particles (MP) contaminate oceans and affect marine organisms in
      several ways. Ingestion combined with food intake is generally reported. However,
      data interpretation often is circumvented by the difficulty to separate MP from
      bulk samples. Visual examination often is used as one or the only step to sort
      these particles. However, color, size, and shape are insufficient and often
      unreliable criteria. We present an extraction method based on hypochlorite
      digestion and isolation of MP from the membrane by sonication. The protocol is
      especially well adapted to a subsequent analysis by Raman spectroscopy. The
      method avoids fluorescence problems, allowing better identification of
      anthropogenic particles (AP) from stomach contents of fish by Raman spectroscopy.
      It was developed with commercial samples of microplastics and cotton along with
      stomach contents from three different Clupeiformes fishes: Clupea harengus,
      Sardina pilchardus, and Engraulis encrasicolus. The optimized digestion and
      isolation protocol showed no visible impact on microplastics and cotton particles
      while the Raman spectroscopic spectrum allowed the precise identification of
      microplastics and textile fibers. Thirty-five particles were isolated from nine
      fish stomach contents. Raman analysis has confirmed 11 microplastics and 13
      fibers mainly made of cellulose or lignin. Some particles were not completely
      identified but contained artificial dyes. The novel approach developed in this
      manuscript should help to assess the presence, quantity, and composition of AP in
      planktivorous fish stomachs.

PMID- 26289817
TI  - Bacillus solani sp. nov., isolated from rhizosphere soil of a potato field.
AB  - A novel Gram-stain-positive, endospore-forming bacterium, designated strain FJAT
      18043T, was isolated from a soil sample of a potato field in Xinjiang Autonomous
      Region, China. Cells were rods that were catalase-positive and motile by
      peritrichous flagella. The strain grew at 20-45  degrees C (optimum 35  degrees
      C), at pH 6.0-10.0 (optimum pH 9) and with 0-10 % (w/v) NaCl (optimum 0 %).
      Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain FJAT
      18043T belonged to the genus Bacillus and exhibited similarities of 97.7, 97.6,
      97.2 and 97.2 % with Bacillus eiseniae A1-2T, Bacillus horneckiae DSM 23495T,
      Bacillus gottheilii WCC 4585T and Bacillus purgationiresistens DS22T,
      respectively. DNA-DNA relatedness between strain FJAT-18043T and B. eiseniae A1-2
      T was lower than 70 % (36.1 %). The menaquinone was identified as MK-7 and the
      major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and
      phosphatidylethanolamine. The major fatty acids detected were anteiso-C15 : 0,
      iso-C15 : 0, iso-C16 : 0, anteiso-C17 : 0, C16 : 0 and iso-C14 : 0. The DNA G+C
      content was 48.8 mol%. Phenotypic, chemotaxonomic and genotypic properties
      clearly indicated that isolate FJAT-18043T represents a novel species within the
      genus Bacillus, for which the name Bacillus solani sp. nov. is proposed. The type
      strain is FJAT-18043T ( = DSM 29501T = CCTCC AB 2014277T).

PMID- 26289816
TI  - Inhibition by stabilization: targeting the Plasmodium falciparum aldolase-TRAP
      complex.
AB  - BACKGROUND: Emerging resistance of the malaria parasite Plasmodium to current
      therapies underscores the critical importance of exploring novel strategies for
      disease eradication. Plasmodium species are obligate intracellular protozoan
      parasites. They rely on an unusual form of substrate-dependent motility for their
      migration on and across host-cell membranes and for host cell invasion. This
      peculiar motility mechanism is driven by the 'glideosome', an actin-myosin
      associated, macromolecular complex anchored to the inner membrane complex of the
      parasite. Myosin A, actin, aldolase, and thrombospondin-related anonymous protein
      (TRAP) constitute the molecular core of the glideosome in the sporozoite, the
      mosquito stage that brings the infection into mammals. METHODS: Virtual library
      screening of a large compound library against the PfAldolase-TRAP complex was
      used to identify candidate compounds that stabilize and prevent the disassembly
      of the glideosome. The mechanism of these compounds was confirmed by biochemical,
      biophysical and parasitological methods. RESULTS: A novel inhibitory effect on
      the parasite was achieved by stabilizing a protein-protein interaction within the
      glideosome components. Compound 24 disrupts the gliding and invasive capabilities
      of Plasmodium parasites in in vitro parasite assays. A high-resolution, ternary X
      ray crystal structure of PfAldolase-TRAP in complex with compound 24 confirms the
      mode of interaction and serves as a platform for future ligand optimization.
      CONCLUSION: This proof-of-concept study presents a novel approach to anti
      malarial drug discovery and design. By strengthening a protein-protein
      interaction within the parasite, an avenue towards inhibiting a previously
      "undruggable" target is revealed and the motility motor responsible for
      successful invasion of host cells is rendered inactive. This study provides new
      insights into the malaria parasite cell invasion machinery and convincingly
      demonstrates that liver cell invasion is dramatically reduced by 95 % in the
      presence of the small molecule stabilizer compound 24.

PMID- 26289819
TI  - Importance of a registered and structured protocol when conducting systematic
      reviews: comments about nebulized antibiotics for ventilator-associated
      pneumonia.

PMID- 26289818
TI  - HAL(r) exoskeleton training improves walking parameters and normalizes cortical
      excitability in primary somatosensory cortex in spinal cord injury patients.
AB  - BACKGROUND: Reorganization in the sensorimotor cortex accompanied by increased
      excitability and enlarged body representations is a consequence of spinal cord
      injury (SCI). Robotic-assisted bodyweight supported treadmill training (BWSTT)
      was hypothesized to induce reorganization and improve walking function.
      OBJECTIVE: To assess whether BWSTT with hybrid assistive limb(r) (HAL(r))
      exoskeleton affects cortical excitability in the primary somatosensory cortex
      (S1) in SCI patients, as measured by paired-pulse somatosensory evoked potentials
      (ppSEP) stimulated above the level of injury. METHODS: Eleven SCI patients took
      part in HAL(r) assisted BWSTT for 3 months. PpSEP were conducted before and after
      this training period, where the amplitude ratios (SEP amplitude following double
      pulses - SEP amplitude following single pulses) were assessed and compared to
      eleven healthy control subjects. To assess improvement in walking function, we
      used the 10-m walk test, timed-up-and-go test, the 6-min walk test, and the lower
      extremity motor score. RESULTS: PpSEPs were significantly increased in SCI
      patients as compared to controls at baseline. Following training, ppSEPs were
      increased from baseline and no longer significantly differed from controls.
      Walking parameters also showed significant improvements, yet there was no
      significant correlation between ppSEP measures and walking parameters.
      CONCLUSIONS: The findings suggest that robotic-assisted BWSTT with HAL(r) in SCI
      patients is capable of inducing cortical plasticity following highly repetitive,
      active locomotive use of paretic legs. While there was no significant correlation
      of excitability with walking parameters, brain areas other than S1 might reflect
      improvement of walking functions. EEG and neuroimaging studies may provide
      further information about supraspinal plastic processes and foci in SCI
      rehabilitation.

PMID- 26289820
TI  - The impact of viral hepatitis-related hepatocellular carcinoma to post-transplant
      outcomes.
AB  - Hepatocellular carcinoma (HCC) is the most common complication of HCV infection
      leading to liver transplantation. We evaluated the impact of aetiology of liver
      disease on patient and graft survival following liver transplantation for HCC.
      From the Scientific Registry of Transplant Recipients (2002-2011), all adults who
      underwent liver transplantation for HCC were retrospectively included. Aetiology
      of liver disease was grouped into HCV, HBV, HCV-HBV co-infection and nonviral
      liver disease. Of 8,733 liver transplant recipients with HCC, 5507 had HCV, 631
      had HBV, 163 were co-infected, and 2432 had nonviral causes of liver disease. In
      follow-up (48 +/- 32 months), 8.2% had graft failure and 29.5% died. The mean
      rates of graft failure were 9.5%, 4.7%, 6.1% and 6.4% in HCV, HBV, HCV-HBV co
      infection and nonviral liver disease, respectively (P < 0.0001). Post-transplant
      mortality rate in patients with HBV was 20.2%, HCV 31.0%, HCV-HBV 28.5% and
      nonviral 28.5% (P < 0.0001). This difference was significant starting one year
      post-transplant and became even more prominent later in follow-up. Five-year post
      transplant survival was 64.7% in HCV, 77.7% in HBV, 71.0% in HCV-HBV and 69.1% in
      nonviral HCC (P < 0.0001). A diagnosis of HCV in patients with HCC was also
      independently associated with an increased risk of both graft failure (adjusted
      hazard ratio = 1.84 (1.46-2.33), P < 0.0001) and mortality (1.35 (1.21-1.50), P <
      0.0001) in multivariate analysis. Patients with HCV-related HCC are at higher
      risk of adverse post-transplant outcomes. These patients should be considered for
      preemptive interferon-free antiviral therapy prior to or immediately following
      liver transplantation.

PMID- 26289821
TI  - Selective Interaction of Dopamine with the Self-Assembled Fibrillar Network of a
      Molecular Hydrogel Revealed by STD-NMR.
AB  - A molecular hydrogel formed by a derivative of L-valine with pendant
      isonicotinoyl moieties interacts selectively with protonated dopamine in the
      presence of related compounds such as 3-methylcatechol, and protonated or neutral
      phenethylamine. A two-point interaction with the gel fibers is postulated to
      explain the results. The conclusions are obtained from nuclear magnetic resonance
      saturation transfer experiments (STD-NMR), illustrating how this technique is
      perfectly suited to monitor the interaction of substrates with the fibrillar
      network of a molecular gel. 

PMID- 26289822
TI  - Alignment of site versus adjudication committee-based diagnosis with patient
      outcomes: Insights from the Providing Rapid Out of Hospital Acute Cardiovascular
      Treatment 3 trial.
AB  - BACKGROUND: Adjudication by an adjudication committee in clinical trials plays an
      important role in the assessment of outcomes. Controversy exists regarding the
      utility of adjudication committee versus site-based assessments and their
      relationship to subsequent clinical events. METHODS: This study is a secondary
      analysis of the Providing Rapid Out of Hospital Acute Cardiovascular Treatment-3
      trial, which randomized patients with chest pain or shortness of breath for
      biomarker testing in the ambulance. The emergency department physician diagnosis
      at the time of emergency department disposition was compared with an adjudicated
      diagnosis assigned by an adjudication committee. The level of agreement between
      emergency department and adjudication committee diagnosis was evaluated using
      kappa coefficient and compared to clinical outcomes (30-day re-hospitalization,
      30-day and 1-year mortality). RESULTS: Of the 477 patients, 49.3% were male with
      a median age of 70 years; hospital admission rate was 31.2%. The emergency
      department physicians and the adjudication committee disagreed in 55 cases
      (11.5%) with a kappa of 0.71 (95% confidence interval: 0.64, 0.78). The 30-day re
      hospitalization, 30-day mortality, and 1-year mortality were 22%, 1.9%, and 9.4%,
      respectively. Although there were similar rates of re-hospitalization
      irrespective of adjudication, in cases of disagreement compared to agreement
      between adjudication committee and emergency department diagnosis, there was a
      higher 30-day (7.3% vs 1.2%, p = 0.002) and 1-year mortality (27.3% vs 7.1%, p <
      0.001). CONCLUSION: Despite substantial agreement between the diagnosis of
      emergency department physicians and adjudication committee, in the subgroup of
      patients where there was disagreement, there was significantly worse short-term
      and long-term mortality.

PMID- 26289823
TI  - Ligand Induced Spectral Changes in CdSe Quantum Dots.
AB  - The rational design of ligand molecules has earned lots of attention as an
      elegant means to tailor the electronic and optical properties of semiconductor
      quantum dots (QDs). Aromatic dithiocarbamate molecules, in particular, are known
      to greatly influence the optoelectronic properties of CdSe QDs, red-shifting the
      absorption features and enhancing the photoluminescence. Here, we present an
      integrated computational study, which combines ab initio molecular dynamics and
      excited state calculations including thousands of excitations, aimed at
      understanding the impact of this kind of surface ligand on the optoelectronic
      properties of CdSe QDs. We demonstrate that the valence electronic states of the
      dithiocarbamate molecules, mostly localized in the anchoring moiety, are
      responsible for the red-shift of the absorption features of capped CdSe QDs.
      Ligands develop interfacial electronic states close to the band edges of the
      CdSe, which enhance the absorption features of the QD and might open new channels
      for the radiative decay from the excited state, improving optical emission.
      Hybridized QD/ligand states could also funnel interfacial charge transfer between
      the inorganic core and surface molecules, a process that lies at the heart of
      many photovoltaic and photocatalytic devices. This work may pave the way toward
      the design of new capping ligands that, adsorbed on the QD surface, could provide
      control over the optoelectronic properties of the semiconductor core. 

PMID- 26289824
TI  - Cultivation of an Adaptive Domestic Network for Surveillance and Evaluation of
      Emerging Infections.
AB  - Accomplishments of this program have provided numerous dividends and might
      benefit areas outside infectious diseases. 

PMID- 26289825
TI  - An analysis of the cognitive items of the movement disorders society checklist
      for the diagnosis of dementia in patients with Parkinson's disease.
AB  - OBJECTIVE: Some studies about the Movement Disorders Society checklist for the
      diagnosis of Parkinson's disease (PD) dementia (PDD) suggested that its accuracy
      was not totally satisfactory. Our study focused to evaluate the two items of the
      checklist related to the cognitive assessment. METHODS: We assessed 95
      consecutive patients with a diagnosis of PD using the UPDRS, Hoehn and Yahr,
      Schwab and England scales, Pfeffer Functional Activities Questionnaire, MMSE,
      Clinical Dementia Rating, clock drawing test, verbal fluency test (animals),
      digit span, word list battery of CERAD, Frontal Assessment Battery and the 15
      item Geriatric Depression Scale The cognitive diagnosis was based on the MDS
      diagnostic criteria for PDD. The checklist was completed later by a blinded
      investigator. The data were evaluated using descriptive analysis and calculation
      of sensitivity, and specificity of the checklist for the diagnosis of PDD.
      RESULTS: 33 patients (35%) were diagnosed with PDD. The ROC curve showed that the
      MMSE cut-off score < 26 had the highest accuracy (sensitivity: 94%, specificity:
      55%) for the diagnosis of PDD. Using the checklist with original cut-off scores
      we found sensitivity of 97% and specificity of 58%. Using an alternative way to
      interpret the cognitive assessment of the checklist we found sensitivity of 94%
      and specificity of 89% for the diagnosis of PDD. CONCLUSIONS: Our findings
      suggest that to improve the accuracy of the checklist, it would be necessary to
      adjust the way we use and interpret the cut-off scores of the MMSE and of the
      subtests, without the need to eliminate their use.

PMID- 26289826
TI  - Platelets in cancer. From basic research to therapeutic implications.
AB  - Platelets are well-known for their major role in primary hemostasis and
      thrombosis. Cancer patients frequently manifest thrombotic events and present
      abnormalities in blood coagulation which appear to be linked to altered platelet
      function and turnover. Moreover, numerous studies indicate an intimate cross-talk
      between platelets and tumor growth, angiogenesis and metastatic dissemination.
      Finally, several experimental data and clinical trials suggest possible benefits
      of anti-platelet drugs on some cancers. Here, we will review the current state of
      basic biological research regarding the role of platelets in cancer progression.
      We also critically review the possible clinical applicability of some anti
      platelet therapies to limit tumor growth and prevent metastatic dissemination. 

PMID- 26289827
TI  - Hot-water spraying is a sensitive test for signs of life before dressing and
      scalding in pig abattoirs with carbon dioxide (CO2) stunning.
AB  - This study investigated the benefits of hot-water spraying (HWS) as a diagnostic
      test to verify the absence of signs of life (SOL) before scalding in pigs
      slaughtered with carbon dioxide (CO2) stunning. A total of 37 108 finishing pigs
      from five German abattoirs (A to E) operating at 55 to 571 pigs per hour were
      assessed. Suspended pigs were sprayed onto the muzzle, head and front legs (143
      to 258 s post sticking for 4 to 10 s, 57 degrees C to 72 degrees C). Any active
      movements during HWS were rated as positive test outcomes. In comparison, SOL
      were considered to be absent if a subsequent manual examination was negative and
      no active movements were observed following HWS. The incidence of pigs with
      activity during hot-water spraying (PWA) was restricted to two abattoirs (B:
      0.25%; D: 0.02%; A, C, E: 0.00%). PWA showed movements of facial muscles (88%),
      mouth opening (78%), righting reflex (63%), isolated leg movements (35%) and
      vocalization (4%). The manual examination was positive in 71% of PWA
      (corneal/dazzle reflex: 67%/53%, nasal septum pinch: 33%), whereas all inactive
      pigs tested negative (P99.9% in either case. Any positive manual findings as well
      as any respiratory activity were instantly terminated using a penetrating captive
      bolt. Active movements triggered by the shot were shown to be an indicator for
      SOL (P<0.001). Video analyses revealed that spontaneous movements (SM) following
      sticking were present in 100% of PWA as opposed to 3.1% in pigs without such
      activity (controls). Results for different categories of SM in PWA v. controls
      were as follows: 100% v. 2.6% for mouth opening, 16.0% v. 0.1% for righting
      reflex and 22.0% v. 0.9% for isolated leg movements (all P<0.001). First mouth
      opening after sticking was observed later in PWA (28+/-24 v. 10+/-7 s), but mouth
      openings were observed for a longer period of time (141+/-44 v. 27+/-25 s) (both
      P<0.001). PWA with shorter mouth-opening intervals showed higher movement
      intensities during HWS and more positive manual findings (P<0.05). We conclude
      that HWS is a promising test for SOL. SM and sustained mouth opening in
      particular are indicators for compromised animal welfare and affected pigs should
      be shot by captive bolt. 

PMID- 26289829
TI  - Vibrational microspectroscopy enables chemical characterization of single pollen
      grains as well as comparative analysis of plant species based on pollen
      ultrastructure.
AB  - MAIN CONCLUSION: Chemical imaging of pollen by vibrational microspectroscopy
      enables characterization of pollen ultrastructure, in particular phenylpropanoid
      components in grain wall for comparative study of extant and extinct plant
      species. A detailed characterization of conifer (Pinales) pollen by vibrational
      microspectroscopy is presented. The main problems that arise during vibrational
      measurements were scatter and saturation issues in Fourier transform infrared
      (FTIR), and fluorescence and penetration depth issues in Raman. Single pollen
      grains larger than approx. 15 um can be measured by FTIR microspectroscopy using
      conventional light sources, while smaller grains may be measured by employing
      synchrotron light sources. Pollen grains that were larger than 50 um were too
      thick for FTIR imaging since the grain constituents absorbed almost all infrared
      light. Chemical images of pollen were obtained on sectioned samples, unveiling
      the distribution and concentration of proteins, carbohydrates, sporopollenins and
      lipids within pollen substructures. The comparative analysis of pollen species
      revealed that, compared with other Pinales pollens, Cedrus atlantica has a higher
      relative amount of lipid nutrients, as well as different chemical composition of
      grain wall sporopollenin. The pre-processing and data analysis, namely extended
      multiplicative signal correction and principal component analysis, offer simple
      estimate of imaging spectral data and indirect estimation of physical properties
      of pollen. The vibrational microspectroscopy study demonstrates that detailed
      chemical characterization of pollen can be obtained by measurement of an
      individual grain and pollen ultrastructure. Measurement of phenylpropanoid
      components in pollen grain wall could be used, not only for the reconstruction of
      past environments, but for assessment of diversity of plant species as well.
      Therefore, analysis of extant and extinct pollen species by vibrational
      spectroscopies is suggested as a valuable tool in biology, ecology and
      palaeosciences.

PMID- 26289828
TI  - Variation in opsin genes correlates with signalling ecology in North American
      fireflies.
AB  - Genes underlying signal reception should evolve to maximize signal detection in a
      particular environment. In animals, opsins, the protein component of visual
      pigments, are predicted to evolve according to this expectation. Fireflies are
      known for their bioluminescent mating signals. The eyes of nocturnal species are
      expected to maximize the detection of conspecific signal colours emitted in the
      typical low-light environment. This is not expected for species that have
      transitioned to diurnal activity in bright daytime environments. Here, we test
      the hypothesis that opsin gene sequence plays a role in modifying firefly eye
      spectral sensitivity. We use genome and transcriptome sequencing in four firefly
      species, transcriptome sequencing in six additional species and targeted gene
      sequencing in 28 other species to identify all opsin genes present in North
      American fireflies and to elucidate amino acid sites under positive selection. We
      also determine whether amino acid substitutions in opsins are linked to
      evolutionary changes in signal mode, signal colour and light environment. We find
      only two opsins, one long wavelength and one ultraviolet, in all firefly species
      and identify 25 candidate sites that may be involved in determining spectral
      sensitivity. In addition, we find elevated rates of evolution at transitions to
      diurnal activity, and changes in selective constraint on long wavelength opsin
      associated with changes in light environment. Our results suggest that changes in
      eye spectral sensitivity are at least partially due to opsin sequence. Fireflies
      continue to be a promising system in which to investigate the evolution of
      signals, receptors and signalling environments. 

PMID- 26289830
TI  - Water-Soluble Iridium-NHC-Phosphine Complexes as Catalysts for Chemical Hydrogen
      Batteries Based on Formate.
AB  - Molecular hydrogen, obtained by water electrolysis or photocatalytic water
      splitting, can be used to store energy obtained from intermittent sources such as
      wind and solar power. The storage and safe transportation of H2 , however, is an
      open and central question in such a hydrogen economy. Easy-to-synthesize, water
      soluble iridium-N-heterocyclic carbene-phosphine (Ir(I) -NHC-phosphine) catalysts
      show unprecedented high catalytic activity in dehydrogenation of aqueous sodium
      formate. Fast reversible generation and storage of hydrogen can be achieved with
      these catalysts by a simple decrease or increase in the hydrogen pressure,
      respectively. 

PMID- 26289831
TI  - Self protein-protein interactions are involved in TPPP/p25 mediated microtubule
      bundling.
AB  - TPPP/p25 is a microtubule-associated protein, detected in protein inclusions
      associated with various neurodegenerative diseases. Deletion analysis data show
      that TPPP/p25 has two microtubule binding sites, both located in intrinsically
      disordered domains, one at the N-terminal and the other in the C-terminal domain.
      In copolymerization assays the full-length protein exhibits microtubule
      stimulation and bundling activity. In contrast, at the same ratio relative to
      tubulin, truncated forms of TPPP/p25 exhibit either lower or no microtubule
      stimulation and no bundling activity, suggesting a cooperative phenomenon which
      is enhanced by the presence of the two binding sites. The binding characteristics
      of the N- and C-terminally truncated proteins to taxol-stabilized microtubules
      are similar to the full-length protein. However, the C-terminally truncated
      TPPP/p25 shows a lower Bmax for microtubule binding, suggesting that it may bind
      to a site of tubulin that is masked in microtubules. Bimolecular fluorescent
      complementation assays in cells expressing combinations of various TPPP/p25
      fragments, but not that of the central folded domain, resulted in the generation
      of a fluorescence signal colocalized with perinuclear microtubule bundles
      insensitive to microtubule inhibitors. The data suggest that the central folded
      domain of TPPP/p25 following binding to microtubules can drive s homotypic
      protein-protein interactions leading to bundled microtubules. 

PMID- 26289832
TI  - Functional morphology of durophagy in black carp, Mylopharyngodon piceus.
AB  - The black carp, Mylopharyngodon piceus (Osteichthyes: Cyprinidae), crushes its
      snail and other molluscan prey with robust pharyngeal jaws and strong bite
      forces. Using gross morphology, histological sectioning, and X-ray reconstruction
      of moving morphology (XROMM), we investigated structural, behavioral, and
      mechanical aspects of pharyngeal jaw function in black carp. Strut-like
      trabeculae in their pharyngeal jaws support large, molariform teeth. The teeth
      occlude with a hypertrophied basioccipital process that is also reinforced with
      stout trabeculae. A keratinous chewing pad is firmly connected to the
      basioccipital process by a series of small bony projections from the base of the
      pedestal. The pharyngeal jaws have no bony articulations with the skull, and
      their position is controlled by five paired muscles and one unpaired median
      muscle. Black carp can crush large molluscs, so we used XROMM to compare
      pharyngeal jaw postures as fish crushed ceramic tubes of increasing sizes. We
      found that black carp increase pharyngeal jaw gape primarily by ventral
      translation of the jaws, with ventral rotation and lateral flaring of the jaws
      also increasing the space available to accommodate large prey items. A stout,
      robust ligament connects left and right jaws together firmly, but allows some
      rotation of the jaws relative to each other. Contrasting with the pharyngeal jaw
      mechanism of durophagous perciforms with fused left and right lower pharyngeal
      jaws, we hypothesize that this ligamentous connection may serve to decouple
      tensile and compressive forces, with the tensile forces borne by the ligament and
      the compressive forces transferred to the prey.

PMID- 26289833
TI  - iMap-Intravascular Ultrasound Radiofrequency Signal Analysis Reflects Plaque
      Components of Optical Coherence Tomography-Derived Thin-Cap Fibroatheroma.
AB  - BACKGROUND: The ability of iMap-intravascular ultrasound (IVUS) tissue
      characterization to detect thin-cap fibroatheroma (TCFA) identified on optical
      coherence tomography (OCT) has not yet been fully elucidated. METHODS AND
      RESULTS: We evaluated 86 coronary lesions from 73 patients with stable angina
      pectoris using iMap-IVUS and OCT. We defined OCT-derived TCFA (OCT-TCFA) as lipid
      rich plaque with a <65-MUm-thick fibrous cap. The external elastic membrane (EEM)
      cross-sectional area (CSA), lumen CSA, plaque plus media (P+M) CSA, plaque burden
      and remodeling index were measured on gray-scale IVUS. Plaque components
      categorized on iMap-IVUS as fibrotic, lipidic, necrotic or calcified are
      presented as absolute area and proportion (%) of total plaque area. OCT-TCFA (22
      lesions) had significantly greater EEM CSA, P+M CSA, plaque burden and remodeling
      index than non-TCFA (64 lesions). Significantly larger %necrotic area, absolute
      lipidic and necrotic areas and smaller %fibrotic areas were found in OCT-TCFA
      than in non-TCFA. On multivariate analysis, absolute necrotic area was an
      independent predictor of OCT-TCFA. The area under the ROC curve for absolute
      necrotic area required to identify OCT-TCFA was 0.86. The sensitivity,
      specificity, positive and negative predictive values of absolute necrotic area
      >=7.3 mm2 for identifying OCT-TCFA were 77%, 88%, 68% and 92%, respectively.
      CONCLUSIONS: Coronary lesions with greater iMap-IVUS absolute necrotic area were
      closely associated with OCT-TCFA.

PMID- 26289834
TI  - Association of Estimated Glomerular Filtration Rate and Proteinuria With Lipid
      Rich Plaque in Coronary Artery Disease.
AB  - BACKGROUND: Estimated glomerular filtration rate (eGFR) and proteinuria are both
      important determinants of the risk of cardiovascular disease and mortality. The
      aim of the present study was to investigate the independent and combined effects
      of eGFR and proteinuria on tissue characterization of the coronary plaques of
      culprit lesions. METHODS AND RESULTS: Conventional intravascular ultrasound and 3
      D integrated backscatter intravascular ultrasound (IB-IVUS) were performed in 555
      patients undergoing elective percutaneous coronary intervention. They were
      divided into 2 groups according to the absence or presence of proteinuria
      (dipstick result >=1+). Patients with proteinuria had coronary plaque with
      significantly greater percentage lipid volume compared with those without (43.6+/
      14.8% vs. 48.6+/-16.1%, P=0.005). Combined analysis was done using eGFR and
      absence or presence of proteinuria. Subjects with eGFR 45-59 ml/min/1.73 m2 and
      proteinuria were significantly more likely to have higher percent lipid volume
      compared with those with eGFR >60 ml/min/1.73 m2 without proteinuria. After
      multivariate adjustment for confounders, the presence of proteinuria proved to be
      an independent predictor for lipid-rich plaque (OR, 1.85; 95% CI: 1.12-3.06,
      P=0.016). CONCLUSIONS: The addition of proteinuria to eGFR level may be of value
      in the risk stratification of patients with coronary artery disease.

PMID- 26289836
TI  - Selective estrogen receptor modulators and the combination therapy conjugated
      estrogens/bazedoxifene: A review of effects on the breast.
AB  - Traditional menopausal hormone therapy containing estrogens/progestin has been
      associated with an increased risk of breast cancer, and estrogen exposure is
      known to promote growth and proliferation of a majority of breast cancers.
      Therefore, it is important for clinicians to consider the breast safety profile
      of any hormone-based therapy used in postmenopausal women. This review provides
      an overview of the breast safety and tolerability profiles of currently marketed
      selective estrogen receptor modulators, antiestrogens, and the first tissue
      selective estrogen complex combining conjugated estrogens with the selective
      estrogen receptor modulator bazedoxifene in postmenopausal women. Selective
      estrogen receptor modulators and antiestrogens act as estrogen receptor
      antagonists in the breast. Tamoxifen, toremifene, and the selective estrogen
      receptor degrader fulvestrant are used to treat breast cancer, and tamoxifen and
      raloxifene protect against breast cancer in high-risk women. Postmenopausal women
      using selective estrogen receptor modulators for prevention or treatment of
      osteoporosis (raloxifene, bazedoxifene) can be reassured that these hormonal
      treatments do not adversely affect their risk of breast cancer and may, in the
      case of raloxifene, even be protective. There are limited data on breast cancer
      in women who use ospemifene for dyspareunia. Conjugated estrogens/bazedoxifene
      use for up to two years did not increase mammographic breast density or breast
      pain/tenderness, and there was no evidence of an increased risk of breast cancer,
      suggesting that conjugated estrogens/bazedoxifene has an improved breast safety
      profile compared with traditional menopausal hormone therapies. Future research
      will continue to focus on development of selective estrogen receptor modulators
      and selective estrogen receptor modulator combinations capable of achieving the
      ideal balance of estrogen receptor agonist and antagonist effects. 

PMID- 26289837
TI  - Extended Clavien-Dindo classification of surgical complications: Japan Clinical
      Oncology Group postoperative complications criteria.
AB  - PURPOSE: Prior to publication of the Clavien-Dindo classification in 2004, there
      were no grading definitions for surgical complications in either clinical
      practice or surgical trials. This report establishes supplementary criteria for
      this classification to standardize the evaluation of postoperative complications
      in clinical trials. METHODS: The Japan Clinical Oncology Group (JCOG)
      commissioned a committee. Members from nine surgical study groups (gastric,
      esophageal, colorectal, lung, breast, gynecologic, urologic, bone and soft
      tissue, and brain) specified postoperative complications experienced commonly in
      their fields and defined more detailed grading criteria for each complication in
      accordance with the general grading rules of the Clavien-Dindo classification.
      RESULTS: We listed 72 surgical complications experienced commonly in surgical
      trials, focusing on 17 gastroenterologic complications, 13 infectious
      complications, six thoracic complications, and several other complications. The
      grading criteria were defined simply and were optimized for surgical
      complications. CONCLUSIONS: The JCOG postoperative complications criteria (JCOG
      PC criteria) aim to standardize the terms used to define adverse events (AEs) and
      provide detailed grading guidelines based on the Clavien-Dindo classification. We
      believe that the JCOG PC criteria will allow for more precise comparisons of the
      frequency of postoperative complications among trials across many different
      surgical fields.

PMID- 26289838
TI  - Efficacy of estrogen replacement therapy (ERT) on uterine growth and acquisition
      of bone mass in patients with Turner syndrome.
AB  - Estrogen replacement therapy (ERT) is necessary for uterine development and bone
      mass acquisition in women with Turner syndrome (TS) suffering from ovarian
      insufficiency. However, adequate ERT regimens have not yet been established. The
      aim of this study was to evaluate the efficacy of ERT for both uterine
      development and bone mass acquisition. One hundred TS patients from Yokohama City
      University Hospital (88 with primary amenorrhea (PA) and 12 patients with
      spontaneous menstrual cycles (MC)) were enrolled after obtaining consent.
      Clinical profiles, uterine length (UL) measured by ultrasonic examination, and
      bone mineral density (BMD) of the lumbar vertebrae (L2-4) assessed by DEXA were
      evaluated. At the time of the first visit, the ULs of patients in the PA group
      were significantly shorter than those in the MC group. After receiving ERT, there
      were no significant differences in UL between patients with PA and MC. Forty
      seven patients for whom the ERT initiation age was known were investigated to
      clarify the influence on BMD. The results showed that the BMD in the late
      initiation (18 years or older) group at the latest visit (0.770 +/- 0.107 g/cm2:
      n = 16) was significantly lower than that in the early initiation (under 18
      years) group (0.858 +/- 0.119 g/cm2: n = 21) or the MC group (0.941 +/- 0.118
      g/cm2: n = 10). No significant differences were seen between the early initiation
      and MC group. ERT was effective in increasing UL and BMD. However, early
      initiation of ERT is necessary to increase BMD.

PMID- 26289839
TI  - Subcutaneous sacral ependymoma--a histopathological challenge.
AB  - Subcutaneous myxopapillary or sacral ependymoma are rare tumors mostly developing
      in children or adolescents. The majority occurs in the sacrococcygeal region.
      There are numerous clinical and histopathological differential diagnoses. Owing
      to the fact that there have been rare reported cases that followed an aggressive
      course and in which the patient succumbed to metastatic disease, long term follow
      up is necessary despite complete excision. We describe here a 25-year-old male
      patient with a histological unusual subcutaneous sacral ependymoma and discuss
      the differential diagnosis as well as treatment options. 

PMID- 26289840
TI  - Presentation of m.3243A>G (MT-TL1; tRNALeu) variant with focal neurology in
      infancy.
AB  - The Mitochondrial tRNALeu (MT-TL1) mutation, m.3243A>G constitutes the commonest
      identified mitochondrial genome mutation. Characteristically, giving rise to
      MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes),
      a phenotypic spectrum associated with this genetic variant is now apparent. We
      report on the first patient with infantile hemiparesis, without comorbid
      encephalopathy, attributed to this variant. This further expands the recognized
      disease spectrum and highlights the need to consider mitochondrial genomic
      mutations in cases of cryptogenic focal neurological deficit in infancy. The
      potential for genetic disease modifiers is additionally discussed.

PMID- 26289842
TI  - The positive correlation between maternal size and offspring size: fitting pieces
      of a life-history puzzle.
AB  - The evolution of investment per offspring (I) is often viewed through the lens of
      the classic theory, in which variation among individuals in a population is not
      expected. A substantial departure from this prediction arises in the form of
      correlations between maternal body size and I, which are observed within
      populations in virtually all taxonomic groups. Based on the generality of this
      observation, we suggest it is caused by a common underlying mechanism. We pursue
      a unifying explanation for this pattern by reviewing all theoretical models that
      attempt to explain it. We assess the generality of the mechanism upon which each
      model is based, and the extent to which data support its predictions. Two classes
      of adaptive models are identified: models that assume that the correlation arises
      from maternal influences on the relationship between I and offspring fitness
      [w(I)], and those that assume that maternal size influences the relationship
      between I and maternal fitness [W(I)]. The weight of evidence suggests that
      maternal influences on w(I) are probably not very general, and even for taxa
      where maternal influences on w(I) are likely, experiments fail to support model
      predictions. Models that assume that W(I) varies with maternal size appear to
      offer more generality, but the current challenge is to identify a specific and
      general mechanism upon which W(I) varies predictably with maternal size. Recent
      theory suggests the exciting possibility that a yet unknown mechanism modifies
      the offspring size-number trade-off function in a manner that is predictable with
      respect to maternal size, such that W(I) varies with size. We identify two
      promising avenues of inquiry. First, the trade-off might be modified by energetic
      costs that are associated with the initiation of reproduction ('overhead costs')
      and that scale with I, and future work could investigate what specific overhead
      costs are generally associated with reproduction and whether these costs scale
      with I. Second, the trade-off might be modified by virtue of condition-dependent
      offspring provisioning coupled with metabolic factors, and future work could
      investigate the proximate cause of, and generality of, condition-dependent
      offspring provisioning. Finally, drawing on the existing literature, we suggest
      that maternal size per se is not causatively related to variation in I, and the
      mechanism involved in the correlation is instead linked to maternal nutritional
      status or maternal condition, which is usually correlated with maternal size.
      Using manipulative experiments to elucidate why females with high nutritional
      status typically produce large offspring might help explain what specific
      mechanism underlies the maternal-size correlation.

PMID- 26289841
TI  - Effects of early adversity on young children's diurnal cortisol rhythms and
      externalizing behavior.
AB  - Early adversity is associated with biological and behavioral dysregulation in
      early childhood. We examined whether early adversity (i.e., poverty and
      involvement with child protective services [CPS]) had an indirect effect on
      externalizing behavior through HPA axis dysregulation, specifically blunted
      diurnal cortisol patterns. Participants included 94 children between the ages of
      3.94 and 6.52 years old, who had a history of CPS involvement (n = 53) or no
      history of CPS involvement (n = 41). Cortisol samples were collected at wake-up
      and bedtime across 3 days, and parent-reported externalizing behavior was
      assessed using the Child Behavior Checklist. Results showed that history of CPS
      involvement and poverty were associated with blunted cortisol patterns, which in
      turn led to elevated externalizing behavior. The indirect effect of CPS
      involvement on externalizing behavior through blunted cortisol was significant,
      whereas the indirect effect of poverty on externalizing behavior was
      nonsignificant. Findings add to our understanding of neurobiological mechanisms
      linking early adversity to psychopathology.

PMID- 26289845
TI  - Elevated expression of FoxM1 promotes the tumor cell proliferation in
      hepatocellular carcinoma.
AB  - The Forkhead box M1 (FoxM1) transcription factor plays crucial roles in multiple
      biological processes, including cell proliferation, differentiation, migration,
      and transformation. Recent studies have reported that aberrant expression of
      FoxM1 was found in a variety of human cancers. However, the expression pattern of
      FoxM1 and its clinical significance in human hepatocellular carcinoma (HCC) have
      not been well characterized to date. In this study, the expression of FoxM1 was
      evaluated in 46 pairs of human HCC, the adjacent non-tumorous liver tissues, and
      12 pairs of normal liver tissues by immumohistochemistry. FoxM1 expression was
      upregulated in the HCC (76.09 %) compared with non-tumorous liver tissues (39.13
      %) and normal liver tissues (8.33 %) (P < 0.05). FoxM1 expression was
      significantly associated with tumor stage, tumor size, tumor number, integrality
      of tumor encapsulation, tumor thrombus, and AFP level (P < 0.05). Functionally,
      enforced expression of FoxM1 in HCC cell line (HHCC) remarkably enhanced cell
      proliferation in vitro and in vivo. Further analysis of cell cycle-related
      molecules showed that FoxM1 overexpression increased expressions of cyclin B1 and
      cyclin D1 but reduced expressions of p27(Kip1) and p21(Cip1). Our findings
      suggest that FoxM1 overexpression promotes HCC cell proliferation by cell cycle
      regulation, which is a potential target for hepatocellular carcinoma therapy. 

PMID- 26289847
TI  - RETRACTED ARTICLE: Upregulation of miR-21 and downregulation of miR-494 may serve
      as emerging molecular biomarkers for prediagnostic samples of subjects who
      developed nasopharyngeal carcinoma associates with lymph node metastasis and poor
      prognosis.

PMID- 26289843
TI  - Interaction of human papillomavirus type 16 particles with heparan sulfate and
      syndecan-1 molecules in the keratinocyte extracellular matrix plays an active
      role in infection.
AB  - Oncogenic human papillomaviruses (HPVs) attach predominantly to extracellular
      matrix (ECM) components during infection of cultured keratinocytes and in the
      rodent vaginal challenge model in vivo. However, the mechanism of virion transfer
      from the ECM to receptors that mediate entry into host cells has not been
      determined. In this work we strove to assess the role of heparan sulfate (HS)
      chains in HPV16 binding to the ECM and determine how HPV16 release from the ECM
      is regulated. We also assessed the extent to which capsids released from the ECM
      are infectious. We show that a large fraction of HPV16 particles binds to the ECM
      via HS chains, and that syndecan-1 (snd-1) molecules present in the ECM are
      involved in virus binding. Inhibiting the normal processing of snd-1 and HS
      molecules via matrix metalloproteinases and heparanase dramatically reduces virus
      release from the ECM, cellular uptake and infection. Conversely, exogenous
      heparinase activates each of these processes. We confirm that HPV16 released from
      the ECM is infectious in keratinocytes. Use of a specific inhibitor shows furin
      is not involved in HPV16 release from ECM attachment factors and corroborates
      other studies showing only the intracellular activity of furin is responsible for
      modulating HPV infectivity. These data suggest that our recently proposed model,
      describing the action of HS proteoglycan processing enzymes in releasing HPV16
      from the cell surface in complex with the attachment factor snd-1, is also
      relevant to the release of HPV16 particles from the ECM to promote efficient
      infection of keratinocytes. 

PMID- 26289844
TI  - Modeling population heterogeneity in viral dynamics for chronic hepatitis C
      infection: Insights from Phase 3 telaprevir clinical studies.
AB  - Viral dynamic modelling has proven useful for designing clinical studies and
      predicting treatment outcomes for patients infected with the hepatitis C virus.
      Generally these models aim to capture and predict the on-treatment viral load
      dynamics from a small study of individual patients. Here, we explored extending
      these models (1) to clinical studies with numerous patients and (2) by
      incorporating additional data types, including sequence data and prior response
      to interferon. Data from Phase 3 clinical studies of the direct-acting antiviral
      telaprevir (T; total daily dose of 2250 mg) combined with pegylated-interferon
      alfa and ribavirin (PR) were used for the analysis. The following data in the
      treatment-naive population were reserved to verify the model: (1) a T/PR regimen
      where T was dosed every 8 h for 8 weeks (T8(q8h)/PR) and (2) a T/PR regimen where
      T was dosed twice daily for 12 weeks (T12(b.i.d.)/PR). The resulting model
      accurately predicted (1) sustained virologic response rates for both of these
      dosing regimens and (2) viral breakthrough characteristics of the T8(q8h)/PR
      regimen. Since the observed viral variants depend on the T exposure, the second
      verification suggested that the model was correctly sensitive to the different T
      regimen even though the model was developed using data from another T regimen.
      Furthermore, the model predicted that b.i.d. T dosing was comparable to q8h T
      dosing in the PR-experienced population, a comparison that has not been made in a
      controlled clinical study. The methods developed in this work to estimate the
      variability occurring below the limit of detection for the viral load were
      critical for making accurate predictions.

PMID- 26289846
TI  - Loss of TIM50 suppresses proliferation and induces apoptosis in breast cancer.
AB  - TIM50 is an essential component of TIM23 complex and involved in protein
      translocating into the inner mitochondrial membrane. Here, we found that TIM50
      was increased in breast cancer cells by SILAC. However, its biological functions
      and molecular mechanisms in breast cancer are poorly understood. To gain insight
      into the functions of TIM50 in breast cancer, we constructed two stably
      transfected cell lines and examined TIM50 expression in tissue samples. Our data
      showed that TIM50 expression was increased in breast cancer. The stable
      suppression of TIM50 expression through lentivirus-mediated shRNA was shown to
      inhibit the abilities of cancer cell proliferation and induce apoptosis. What is
      more, depletion of TIM50 could decrease mitochondrial membrane potential, which
      may be associated with cell viability. Taken together, our findings reveal a new
      role for TIM50 in regulating cell proliferation and apoptosis through decreasing
      mitochondrial membrane potential in breast cancer cell and suggest that TIM50
      might be a potential target for controlling breast cancer progression. 

PMID- 26289848
TI  - YT521 promotes metastases of endometrial cancer by differential splicing of
      vascular endothelial growth factor A.
AB  - The malignancy of endometrial carcinoma (EC) largely results from its high
      invasive feature. The regulation of the mRNA splicing of vascular endothelial
      growth factor A (VEGF-A) is critical for EC-associated cancer vascularization and
      invasion. Recently, we have reported that poorly prognostic EC had high levels of
      YT521, a newly defined RNA splicing protein. However, whether YT521 may similarly
      regulate the splicing of VEGF-A in EC is unknown. Here, we showed that EC
      specimens contained significantly higher levels of YT521, compared to the
      adjacent non-tumor endometrial tissue. Higher levels of YT521 were detected in EC
      specimens with metastases. High-YT521 EC is associated with poor patient
      survival. In order to examine whether YT521 may regulate VEGF-A mRNA splicing in
      EC, we transfected an EC cell line HEC-1A with different doses of YT521 mimics.
      We found that YT521 dose-dependently increased the ratio of VEGF-165 vs VEGF-121
      at both mRNA and protein level, suggesting that YT521 may promote VEGF-A mRNA
      splicing to favor a VEGF-165 isoform. Moreover, the increases in the ratio of
      VEGF-165 vs VEGF-121 by YT521 overexpression resulted in increases in EC cell
      invasion, while decreases in the ratio of VEGF-165 vs VEGF-121 by YT521 depletion
      resulted in decreases in EC cell invasion in a transwell cell migration assay.
      Further, overexpression of VEGF-165, but not overexpression of VEGF-121,
      increased EC cell invasiveness. Finally, a strong correlation was detected
      between the ratio of VEGF-165 vs VEGF-121 and the levels of YT521 in EC
      specimens. Together, these data suggest that YT521 may promote EC metastases by
      regulating mRNA splicing of VEGF-A.

PMID- 26289849
TI  - Letter regarding Zhang et al. entitled "Systematic review of high-dose and
      standard-dose chemotherapies in the treatment of primary well-differentiated
      osteosarcoma".

PMID- 26289850
TI  - The assessment of the prognostic value of tumor markers and cytokines as SCCAg,
      CYFRA 21.1, IL-6, VEGF and sTNF receptors in patients with squamous cell cervical
      cancer, particularly with early stage of the disease.
AB  - The aim of this study is to determine the prognostic value of tumor markers, as
      squamous cell carcinoma antigen (SCCAg) and cytokeratin-19 fragment (CYFRA 21.1)
      and interleukin 6 (IL-6), vascular endothelial growth factor (VEGF), soluble
      tumor necrosis factor receptor I (sTNF RI), and sTNF RII in patients with
      squamous cell carcinoma of the cervix. The subjects of analysis were 138 patients
      with stage I-IVA according to the International Federation of Gynecology and
      Obstetrics (FIGO) classification. The collected research material comes from one
      oncology center. During the 10 years of follow-up, 56 relapses and 53 deaths were
      observed, and recurrent disease in early stage was confirmed in 45 % of patients.
      The pretreatment serum levels of SCCAg and CYFRA 21.1, and cytokines IL-6, VEGF,
      sTNF RI, and sTNF RII were determined in all patients. The probability of disease
      free survival (DFS) and overall survival (OS) was evaluated using the log-rank
      test and the Cox regression model. Based on the ROC curve analysis for patients
      with recurrence, the largest area under the curve was demonstrated for SCCAg and
      IL-6 and for patients who died, for SCCAg and VEGF. Cox analysis demonstrated
      that independent prognostic factor for DFS was only SCCAg and for OS cytokine IL
      6 and SCCAg, but in patients with early stage the prognostic value for DFS was
      VEGF, whereas IL-6 and CYFRA 21.1 for OS. Serum level of VEGF, CYFRA 21.1 and IL
      6 before treatment in patients with early stage cervical cancer appears to be an
      important prognostic factor. 

PMID- 26289851
TI  - Antisense-miR-21 enhances differentiation/apoptosis and reduces cancer stemness
      state on anaplastic thyroid cancer.
AB  - Anaplastic thyroid carcinoma (ATC) is the most aggressive malignancy in thyroid
      cancers. Resistance to current therapies is still a challenge. MicroRNAs are a
      class of small non-coding RNAs, regulating gene expression. MiR-21 is an oncomiR
      that is overexpressed in nearly all cancers including ATC. Accumulating evidence
      suggested that miR-21 has a role in cancer stemness state, apoptosis, cell cycle
      progression, and differentiation. Therefore, we evaluated the application of Off
      miR-21 to sequester the microRNA for therapeutic purposes on ATC cell lines. In
      this study, C643 and SW1736 were transducted by hsa-miR-21 antagomir (Off-miR
      21). PTEN gene expression was performed as a known target of miR-21. Stemness
      state in cancer stem cells (CSCs) was evaluated by the changes of CSC biomarkers
      including Oct-4 and ABCG2. Apoptosis was assessed by PDCD4 and Mcl-1 gene
      expression and flow cytometry. Sodium/iodide symporter (NIS) and thyroglobulin
      (TG) were measured as ATC differentiation markers. In addition, cell cycle
      progression was investigated via the alterations of p21 gene expression and flow
      cytometry. Specific downregulation of miR-21 induced the differentiation and
      apoptosis in C643 and SW1736. Inversely, the treatment inhibited stemness state
      and cell cycle progression. Knockdown of miR-21 significantly increased the
      expression of PDCD4, p21, NIS, and TG while leading to decreased expression of
      Oct-4, ABCG2, and Mcl-1.Taken together, the results suggest that miR-21, as an
      oncomiR, has a role not only in stemness state but also in tumor growth,
      differentiation, and apoptosis. Hence, suppression of miR-21 could pave the way
      for ATC therapy. 

PMID- 26289853
TI  - [Vaccination against Herpes Zoster after 50 years-of-age is effective].

PMID- 26289852
TI  - Identification of a panel of complex autoantigens (LGALS3, PHB2, MUC1, and GK2)
      in combination with CA15-3 for the diagnosis of early-stage breast cancer.
AB  - Currently, there is no effective single antigen and there are only a very limited
      number of complex antigens for the diagnosis of early-stage breast cancer (BC).
      In this study, we used serological analysis of recombinant cDNA expression
      libraries (SEREX) in combination with phage display technology to screen complex
      autoantigens from the sera of BC patients. The cDNA expression library was
      constructed using tissue samples of three patients with BC at as early as stage
      T1N0M0. The serum samples of ten patients, including the three patients who
      provided tissue samples, as well as five healthy human subjects as controls were
      used to screen the library. All seven autoantigens were identified from the
      library by four rounds of screening and matched the existing genes after a blast
      search using NCBI-BLAST. Then, the expression conditions of the autoantibodies of
      the seven autoantigens and anti-CA15-3 in the sera from 100 BC patients and 50
      healthy donors were examined by gray values. The data were analyzed by the area
      under the receiver operating characteristic (ROC) curve and logistic regression
      diagnostic models. In the end, a panel of complex autoantigens consisting of B11
      (LGALS3), B18 (PHB2), B119 (MUC1), B130 (GK2), and CA15-3, which had a
      sensitivity of 87 % and a specificity of 76 %, were identified. The area under
      the curve (AUC) of the complex antigens was 0.872, which is significantly greater
      than that of anti-CA15-3 alone (AUC = 0.634) for the diagnosis of BC. Thus, this
      panel of complex antigens provides a promising strategy for the diagnosis of
      early-stage BC. 

PMID- 26289854
TI  - [Optimized workflow].

PMID- 26289855
TI  - [The cervical spine is compressing the esophagus].

PMID- 26289856
TI  - [Vaccination against malaria is within reach now].

PMID- 26289857
TI  - [First success with Ebola vaccine].

PMID- 26289858
TI  - [What helps in tormenting mosquito bites].

PMID- 26289859
TI  - [Include nursing care services in the physician network!].

PMID- 26289860
TI  - [Seniors are using waiting room for jam session].

PMID- 26289861
TI  - [The cardiologist from Indonesia gets lost].

PMID- 26289862
TI  - [Patient discharge will be improved].

PMID- 26289863
TI  - [Second opinion: we will wait for implementation!].

PMID- 26289864
TI  - [Can I now claim electric stimulation treatment?].

PMID- 26289865
TI  - [We physicians have the responsibility to integrate IT into therapy].

PMID- 26289866
TI  - [Prevent accidental falls!].

PMID- 26289867
TI  - [Investigating the cause of syncope].

PMID- 26289868
TI  - [How AMOG limits the supply of diabetes drugs].

PMID- 26289869
TI  - [Early weight reduction prevents complication].

PMID- 26289870
TI  - [Does stress increase diabetes risk?].

PMID- 26289871
TI  - [In every patient contact emphasize the issue].

PMID- 26289872
TI  - [Dying with dignity - with the defibrillator in the chest?].

PMID- 26289873
TI  - [Agreement on appropriate treatment goals].

PMID- 26289875
TI  - [Seniors are inclined to have complicated appendicitis].

PMID- 26289874
TI  - [Paracetamol is ineffective in back pain].

PMID- 26289876
TI  - [First NOAK antidote soon to be approved].

PMID- 26289877
TI  - [Grinning from the edge of the cecum].

PMID- 26289878
TI  - [Pelvic floor training helps in prolapse symptoms].

PMID- 26289879
TI  - [Less budesonide after collagen colitis].

PMID- 26289880
TI  - [Descent into hypothyroid coma].

PMID- 26289881
TI  - [Apparently diabetes does not promote cancer].

PMID- 26289882
TI  - [And when the red line reaches the heart?].

PMID- 26289883
TI  - [Cancer diagnosis: no need to despair].

PMID- 26289884
TI  - [Chemotherapy is better than its reputation: important developments within the
      last decades].

PMID- 26289885
TI  - [Radiotherapy in oligometastatic disease].

PMID- 26289886
TI  - [Multimodal treatment of colorectal liver metastases].

PMID- 26289887
TI  - [Ebola outbreak in Westafrica].

PMID- 26289888
TI  - [Multimodal treatment of patients with addictions after detoxification].

PMID- 26289889
TI  - [Earache after aquatic vacation].

PMID- 26289890
TI  - [Pain everywhere and no findings - fibromyalgia].

PMID- 26289891
TI  - ["Can you climb 2 floors without pausing"].

PMID- 26289892
TI  - [Better treatment options in sight].

PMID- 26289893
TI  - [Artichoke extract with prokinetic effect].

PMID- 26289894
TI  - [Relieve your patients of angina pectoris symptoms].

PMID- 26289895
TI  - [LAMA/LABA or LABA/ICS?].

PMID- 26289896
TI  - [Even lower values are even better!].

PMID- 26289897
TI  - [High health care costs].

PMID- 26289898
TI  - [Rising demand for immunodiagnosis].

PMID- 26289899
TI  - [Dual bronchodilatation in a fine spray cloud].

PMID- 26289900
TI  - [Therapy discontinuation after many years of virus suppression is possible].

PMID- 26289901
TI  - [Nocturnal leg cramps].

PMID- 26289902
TI  - Interpreting Injury Mechanisms of Blunt Force Trauma from Butterfly Fracture
      Formation.
AB  - According to biomechanics of fracture production during blunt impact, tubular
      bones are subject to compressive (impact site) and tensile (opposite impact site)
      forces; this causes bones to break in tension before compression, producing Y
      shaped fracture patterns with breakaway (butterfly) fragments. In current
      forensic models, the side of the bone exhibiting the breakaway fragment is
      designated the impact side, with initial breakage occurring opposite. Fracture
      production and patterning of blunt impacts to 255 sheep femora were analyzed.
      Contra the existing model, only 60% of complete butterfly fractures exhibited
      impact side breakaway fragments. Although fractures initiated on the tension,
      nonimpact side, butterfly fragments formed on either compression or tension
      sides. Using newly defined breakaway fragment shape criteria, impact side was
      estimated with 98% accuracy for both complete and partial butterfly fractures.
      Furthermore, the results suggest that the impact site is the located on one of
      the Y-fracture's arms, not the butterfly fragment's center, as previously
      modeled.

PMID- 26289903
TI  - First direct evidence of a Patent Foramen Ovale (PFO): a large thrombus
      straddling the foramen ovale.

PMID- 26289904
TI  - Lowering cholesterol in chronic kidney disease: is it safe and effective?
AB  - The value of cholesterol lowering in preventing cardiovascular disease has now
      been established in patients with chronic kidney disease (CKD), who are
      intrinsically at high cardiovascular risk. While data from completed studies has
      clearly demonstrated substantive benefit of statins in early CKD, the effects in
      end-stage CKD remain controversial. Recent studies have also suggested that the
      effects of different statins on the kidney may be heterogeneous, and the safety
      of high-dose statins in this population remains uncertain. Communications from
      regulators such as the US Food and Drug Administration concerning potential side
      effects of statin therapy (particularly memory loss and the risk of diabetes)
      have created debate in the medical literature and unrest in the public mind about
      the value of long-term statin therapy for vulnerable patient populations. The
      evaluation of risks and benefits for this class of agents is critically dependent
      on baseline risk. This article will review current evidence for the benefits and
      risks of statin therapy for kidney and cardiovascular disease progression in the
      CKD population. 

PMID- 26289905
TI  - Distance- and near-visual impairment in rural Chinese adults in Kailu, Inner
      Mongolia.
AB  - PURPOSE: To investigate the prevalence and causes of distance-visual impairment
      and near-vision impairment in a rural Chinese population in Inner Mongolia.
      METHODS: A population-based, cross-sectional study design was used to identify
      visual impairment in the Chinese aged 40 years and older living in Kailu County,
      Inner Mongolia. Low vision, blindness and near-visual impairment (NVI) were
      defined according to World Health Organization (WHO) criteria. RESULTS: The
      overall prevalence of blindness and visual impairment based on the presenting
      visual acuity (VA) was 2.2% (95% CI: 1.8-2.6) and 9.8% (95% CI: 8.9-10.6),
      respectively, and was adjusted to 0.9% (95% CI: 0.6-1.2) and 4.7% (95% CI: 4.1
      5.3) using best-corrected visual acuity (BCVA), respectively. Taking the
      presenting VA into consideration, the leading cause of visual impairment and
      blindness was cataract (40.3%, 40.9%), followed by uncorrected refractive error
      (26.6%, 28.2%). According to the BCVA, the main cause of visual impairment and
      blindness was cataract (48.3%, 41.3%) followed by glaucoma (19.0%, 23.9%). Among
      the examined subjects, 80.3% had NVI, and 51.7% had presbyopia. Major barriers
      reported by NVI persons without near correction were lack of money to purchase
      prescription glasses and poor quality of the available ones (43.2%). CONCLUSION:
      Visual impairment is a serious public health problem, and the main causes leading
      to visual impairment are treatable and preventable in the rural Chinese
      population in Inner Mongolia. Presbyopia, together with the low rate of
      spectacles and lack of appropriate refractive and presbyopia spectacles, is
      highly prevalent in rural China.

PMID- 26289906
TI  - Erectile dysfunction in 1050 men following extended (18 cores) vs saturation (28
      cores) vs saturation plus MRI-targeted prostate biopsy (32 cores).
AB  - Erectile dysfunction (ED) following transperineal prostate biopsy (TPB) was
      prospectively evaluated. From January 2011 to January 2014, 1050 patients were
      submitted to TPB: 18 core (extended TPB) in 610 cases, 28 core (saturation TPB)
      in 360 cases and 32 core (saturation plus magnetic resonance imaging (MRI)
      targeted TPB) in 210 cases. The indications for biopsy were increasing prostate
      specific antigen (PSA) or PSA>10 ng ml(-1). All patients were prospectively
      evaluated with the 5-item version of the International Index of Erectile Function
      (IIEF-5) at time zero and at 1, 3 and 6 months from TPB. Prostate cancer was
      diagnosed in 385/1050 (36.6%) patients; 560 men (350 vs 110 vs 100) having benign
      histology and normal sexual activity also completed the study. Overall, IEEF-5
      score at time zero and at 1, 3 and 6 months did not significantly worsen
      (P>0.05); in detail, at 1 month from biopsy 15 extended TPB (4.2%) vs 7
      saturation TPB (6.4%) vs 7 saturation plus MRI targeted TPB (7%) men referred
      mild ED that disappeared after 3 months. Irrespective of method (18 vs 28 vs 32
      core) TPB did not significantly worsen erectile function at 3-6 months from the
      procedure.

PMID- 26289908
TI  - A Study of the Solvation Structure of L-Leucine in Alcohol-Water Binary Solvents
      through Molecular Dynamics Simulations and FTIR and NMR Spectroscopy.
AB  - The solvation structures of l-leucine (Leu) in aliphatic-alcohol-water and
      fluorinated-alcohol-water solvents are elucidated for various alcohol contents by
      using molecular dynamics (MD) simulations and IR, and (1) H and (13) C NMR
      spectroscopy. The aliphatic alcohols included methanol, ethanol, and 2-propanol,
      whereas the fluorinated alcohols were 2,2,2-trifluoroethanol and 1,1,1,3,3,3
      hexafluoro-2-propanol. The MD results show that the hydrophobic alkyl moiety of
      Leu is surrounded by the alkyl or fluoroalkyl groups of the alcohol molecules. In
      particular, TFE and HFIP significantly solvate the alkyl group of Leu. IR spectra
      reveal that the Leu C-H stretching vibration blueshifts in fluorinated alcohol
      solutions with increasing alcohol content, whereas the vibration redshifts in
      aliphatic alcohol solutions. When the C-H stretching vibration blueshifts in the
      fluorinated alcohol solutions, the hydrogen and carbon atoms of the Leu alkyl
      group are magnetically shielded. Consequently, TFE and HFIP molecules may solvate
      the Leu alkyl group through the blue-shifting hydrogen bonds. 

PMID- 26289909
TI  - Comparison of field-in-field radiotherapy with conformal radiotherapy for
      unilateral cervical malignant lymphoma.
AB  - This study compared field-in-field (FIF) radiotherapy with conformal radiotherapy
      with physical wedges for the treatment of unilateral cervical malignant lymphoma.
      Two treatment plans, the FIF technique and conformal RT, were generated for each
      of 32 patients with unilateral cervical malignant lymphoma. To compare the 2
      treatment plans, dose-volume histograms of the planning target volume (PTV), the
      thyroid, submandibular gland, carotid artery, mucosa, spinal cord, and
      surrounding normal tissue, and monitor unit (MU) were analyzed. The FIF technique
      showed significant reduction in the mean dose of thyroid, submandibular gland,
      carotid artery and mucosa, the maximum dose of the spinal cord and PTV, and the
      volume receiving>107% of the prescribed dose of surrounding normal tissue
      (p<0.001). In addition, there were gains in the homogeneity index of the PTV for
      FIF. Furthermore, the total MU was also lower for the FIF technique than for the
      wedge technique (p<0.001). Compared with the wedge technique, the FIF technique
      improved the dose homogeneity of the PTV, reduced the dose to normal structures,
      and was associated with fewer MUs in the treatment of patients with cervical
      malignant lymphoma. 

PMID- 26289910
TI  - Hemodynamic effects of intravenous calcium administration on septic shock
      patients: a retrospective study.
AB  - We evaluated the hemodynamics and outcomes of septic shock (SS) patients who did
      not respond to fluid resuscitation, after treatment with or without intravenous
      calcium. We retrospectively collected information on 154 eligible SS patients who
      were admitted to Fukuyama City Hospital Emergency Medical Center and did not
      respond to fluid resuscitation. To compare their degree of hemodynamic
      impairment, we compared the changes in the vasoactive-inotropic score (VIS) in
      the calcium-treated group (n=112) and the noncalcium-treated group (n=42). We
      compared the length of stay in the intensive care unit (ICU) and hospital, in
      hospital deaths, 28-day deaths, and changes in the Sequential Organ Failure
      Assessment score within 72h of ICU admission between the 2 groups. Changes in the
      VIS at 1h after the baseline time were significantly greater in the calcium
      treated group than in the noncalcium-treated group (1.41 vs. -1.25,
      respectively;p<0.001). However, the changes in the VIS at 3, 6, 24, 48, and 72h
      did not differ between the 2 groups. The secondary outcomes also did not differ
      between the groups. Our findings indicate that calcium administered to SS
      patients might reduce their hemodynamic stabilization, but only for a short time
      after its administration. 

PMID- 26289907
TI  - The safety and efficacy of clomiphene citrate in hypoandrogenic and subfertile
      men.
AB  - Our objective was to evaluate the safety and efficacy of clomiphene citrate (CC)
      in infertile and hypoandrogenic men through a retrospective study between
      September 2013 and May 2014. We identified 47 men between 18 and 55 years placed
      on 50 mg CC every other day. We evaluated the effect of CC on testosterone after
      2 weeks, rates of adverse effects and predictors of CC response. Mean baseline
      testosterone, bioavailable testosterone and estradiol were 246.8 ng dl(-1), 125.5
      ng dl(-1) and 20.8 pg dl(-1), respectively. At 2 weeks, mean testosterone,
      bioavailable testosterone and estradiol increased to 527.6 ng dl(-1), 281.8 ng
      dl(-1) and 32.0 pg dl(-1) (all P<0.001). Two patients at 2 weeks and one patient
      at 3 months had a paradoxical decrease in testosterone. Mean total motile count
      (TMC) and concentration increased from 59.7 million (s.e.m.: 16.5) and 50.7
      millions ml(-1) (s.e.m.: 11.1) at baseline to 90.9 million (s.e.m.: 25.9) and
      72.5 millions ml(-1) (s.e.m.: 17.5), respectively, at 3 months, although this was
      nonsignificant (P=0.09, 0.09). No patient on CC experienced a paradoxical
      decrease in TMC or sperm concentration. On age-adjusted regression analysis, age,
      BMI, longitudinal testis axis, baseline follicle-stimulating hormone, LH and
      estradiol did not correlate with improvement in bioavailable testosterone at 2
      weeks. CC improves testosterone and may improve semen parameters, although a
      small percentage of men may not demonstrate improvement in testosterone. 

PMID- 26289911
TI  - Venous thromboembolism after total hip arthroplasty diagnosed by enhanced
      computed tomography:comparison of selective thromboprophylaxis and no
      thromboprophylaxis.
AB  - Total hip arthroplasty (THA) is the most effective treatment for advanced or end
      stage hip osteoarthritis. However, venous thromboembolism (VTE) remains one of
      its unresolved complications. We reviewed the records of 322 patients undergoing
      primary THA and investigated the efficacy of anticoagulant prophylaxis for VTE.
      Our study cohort consisted of 60 patients who received no anticoagulants, 100
      patients who received a factor Xa inhibitor (fondaparinux), 100 patients who
      received low molecular weight heparin (enoxaparin), and 62 patients who
      selectively received no anticoagulant prophylaxis due to perioperative bleeding,
      weight, and/or hemoglobin concentration. Enhanced 64-slice multidetector row
      computed tomography was performed postoperatively for 7 days in all cases. The
      incidence of VTE in the four groups was 15%, 9.0%, 6.0%, and 6.4%, respectively.
      The incidence of VTE was significantly lower in the groups receiving
      anticoagulant prophylaxis and the group selectively receiving no anticoagulant
      prophylaxis than in the group receiving no anticoagulants. Complications of
      fondaparinux therapy included hepatic dysfunction in 4 cases (4.0%), minor
      bleeding in 2 cases (2.0%), persistent wound drainage in 3 cases (3.0%), and
      eruption in 1 case (1.0%). The complications of enoxaparin therapy were
      persistent wound drainage in 1 case (1.0%) and progression of anemia in 1 case
      (1.0%). The incidence of VTE was low in patients who selectively received no
      anticoagulant prophylaxis, so we conclude that anticoagulant prophylaxis should
      be used selectively in THA cases. 

PMID- 26289912
TI  - Prevalence, risk factors, and short-term consequences of traumatic brain injury
      associated hyponatremia.
AB  - Hyponatremia, a common electrolyte disorder associated with traumatic brain
      injuries (TBIs), has high mortality and morbidity rates. The aim of this study
      was to identify the risk factors for hyponatremia associated with TBI. We
      retrospectively analyzed the cases of TBI patients who were admitted to the
      emergency intensive care unit at Okayama University Hospital between October 2011
      and September 2014. A total of 82 TBI patients were enrolled. The incidences of
      hyponatremia (serum sodium level of<135mEq/L) and severe hyponatremia (serum
      sodium level of<130mEq/L) within the first 14 days after admission were 51%
      (n=42) and 20% (n=16), respectively. After admission, hyponatremia took a median
      period of 7 days to develop and lasted for a median of 3 days. Multivariate
      analysis demonstrated that higher fluid intake from days 1 to 3 and the presence
      of cranial fractures were risk factors for hyponatremia. The 58 patients with
      hyponatremia experienced fewer ventilator-free days, longer intensive care unit
      stays, and less favorable outcomes compared to the 24 patients without
      hyponatremia;however, these differences were not significant. Further studies are
      needed to determine the optimal management strategy for TBI-associated
      hyponatremia in the intensive care unit setting. 

PMID- 26289913
TI  - Local recurrence and complications after percutaneous radiofrequency ablation of
      hepatocellular carcinoma: a retrospective cohort study focused on tumor location.
AB  - We conducted a retrospective cohort study to investigate the predisposing factors
      for local recurrence and complications after percutaneous radiofrequency ablation
      (RFA) of hepatocellular carcinoma (HCC). HCC patients (n=397) consecutively
      treated with RFA (256 males, 141 females, median age 69 years) were enrolled. In
      these patients, 1,455 nodules (median size 17mm) were ablated. Predisposing
      factors for overall recurrence and local recurrence in the context of tumor
      location and complications were examined. Local recurrence was observed for 113
      of the 1,455 nodules. The 1-, 3- and 5-year local recurrence rates were 2.2%,
      7.4% and 9.5%, respectively. A multivariate Cox proportional hazard analysis
      revealed that large tumor size (>2cm), tumor location (adjacent to the major
      portal branch or hepatic vein), and small ablated margin (<3mm) were independent
      predisposing factors for local recurrence after RFA (HR=1.70-2.81). Tumor
      location (adjacent to the major portal branch, hepatic vein, or diaphragm) was
      also revealed as a risk factor for liver damage due to RFA. HCC adjacent to the
      major portal vein or hepatic vein was associated with a higher risk for local
      recurrence and for complications;therefore, special precautions are necessary
      when applying RFA to HCC near vessels even when the tumors are located at an easy
      to-puncture site. 

PMID- 26289914
TI  - Reactivity of CA19-9 and CA125 in histological subtypes of epithelial ovarian
      tumors and ovarian endometriosis.
AB  - Previous reports have shown that some ovarian endometrioid adenocarcinomas and
      ovarian clear cell adenocarcinomas derive from ovarian endometriosis (OE), and
      that endocervical-like mucinous borderline ovarian tumors are associated with OE.
      We examined the relationship between the staging and histological subtypes of OE
      or epithelial ovarian tumors (EOT) and the serum levels of carbohydrate antigen
      19-9 (CA19-9) and carbohydrate antigen 125 (CA125) to evaluate the potential of
      these markers for preoperative diagnosis. First, we analyzed the preoperative
      serum levels of CA19-9 and CA125 in 195 patients who were histopathologically
      diagnosed with OE or EOT. We then performed a case-control study in which 308
      women were enrolled, the 195 women described above and 113 healthy women as
      control subjects. Serum CA19-9 and CA125 levels were found to be useful in
      differentiating between OE and serous adenocarcinoma, but not between OE and
      other EOT. Moreover, serum CA19-9 levels were useful for preoperative assessment
      between OE and stage I mucinous borderline ovarian tumors, with or without the
      interstitial infiltration. In addition, considering that the serum CA19-9 levels
      in stage I mucinous borderline ovarian tumors were elevated via the interstitial
      infiltration of leukocytes and that precancerous lesions are associated with a
      cancerous glycosylation disorder in the process of inflammatory carcinogenesis,
      the CA19-9 level may be considered a suitable biomarker for estimating drug
      susceptibility. 

PMID- 26289915
TI  - Effectiveness of extending treatment duration in therapy with pegylated
      interferon and ribavirin for genotype 2 hepatitis C virus infection.
AB  - The effectiveness of extending treatment duration as response guided therapy was
      previously reported for chronic hepatitis C (CHC) genotype 1, but is still
      controversial for genotype 2. The present study is a retrospective cohort study
      to investigate the effectiveness of extending treatment duration in therapy with
      pegylated interferon and ribavirin for patients with CHC genotype 2 by focusing
      on the timing at which patients obtained undetectable HCV RNA. A total of 306
      patients who obtained undetectable HCV RNA by week 24 of treatment and completed
      24 weeks of treatment were enrolled. Rapid virological response (RVR) to standard
      therapy was achieved by 122 patients (51%), and 89% of them obtained sustained
      virological response (SVR), while 69% of non-RVR patients achieved SVR. Non-RVR
      patients with undetectable HCV RNA at week 8, and insufficient adherence<80%
      pegylated interferon and ribavirin during the first 24 weeks, significantly
      improved their SVR rate by extended therapy. Among patients receiving extended
      therapy, drug adherences did not differ between SVR and non-SVR patients,
      indicating that extending treatment duration might compensate for insufficient
      antiviral effects due to insufficient drug adherences. This finding might be
      useful in creating a guideline for extending treatment duration for patients with
      CHC genotype 2. 

PMID- 26289916
TI  - The effects of self-directed home exercise with serial telephone contacts on
      physical functions and quality of life in elderly people at high risk of
      locomotor dysfunction.
AB  - Exercise is essential for maintaining quality of life (QOL) in elderly
      individuals. However, adherence to exercise programs is low. Here, we assessed
      the effectiveness of a self-directed home exercise program with serial telephone
      contacts to encourage exercise adherence among elderly individuals at high risk
      of locomotor dysfunction. We recruited community-dwelling adults (?65 years) in
      Niigata, Japan, who were targets of the long-term care prevention project for
      locomotor dysfunction but did not participate in the government-sponsored
      prevention programs. The study was conducted from November 2011 to October 2012.
      Participants received exercise instruction and performed exercises independently
      for 3 months with serial telephone contacts. The single-leg stance and five-times
      sit-to-stand tests were used to assess physical function. The SF-8 was used to
      measure health-related QOL. Ninety-seven participants were enrolled in the study,
      representing 2.5% of eligible people;87 completed the intervention. Scores from
      physical function tests were significantly improved by the intervention, as were
      7 of eight SF-8 subscales. Adherence was 85.4% for the single-leg standing
      exercise and 82.1% for squatting. Thus, self-directed home exercise with serial
      telephone contacts improved physical function and health-related QOL,
      representing a promising model for preventing the need for long-term care due to
      locomotor dysfunction. 

PMID- 26289917
TI  - Changes in the features of invasive pneumococcal disease after introduction of
      the seven-valent pneumococcal conjugate vaccine in a regional core hospital of
      Kochi, Japan.
AB  - Since the introduction of the seven-valent pneumococcal conjugate vaccine (PCV7)
      in 2007, invasive pneumococcal disease has declined, but the incidence of
      Streptococcus pneumoniae serotype 19A has risen worldwide. The present study
      examined changes in the features of invasive pneumococcal disease since the
      introduction of the PCV7 in Kochi, Japan. Pediatric cases of invasive
      pneumococcal disease were investigated before and after vaccine introduction
      (January 2008 to December 2013). Cases of invasive pneumococcal disease tended to
      decrease after PCV7 introduction. In addition, before introduction of the
      vaccine, most serotypes causing invasive pneumococcal disease were those included
      in the vaccine. However, after the introduction, we found cases infected by
      serotypes not covered by vaccine. Penicillin-resistant S. pneumoniae was the
      predominant serotype causing invasive pneumococcal disease before introduction of
      the PCV7, and the susceptibility of this serotype to antibiotics improved after
      vaccine introduction. Serotype isolates identified after vaccine introduction
      were also relatively susceptible to antibiotic therapy, but decreased
      susceptibility is expected. 

PMID- 26289918
TI  - Sense of belonging to local community in small-to-medium sized Canadian urban
      areas: a comparison of immigrant and Canadian-born residents.
AB  - BACKGROUND: Sense of belonging is recognized as an important determinant of
      psychological and physical well-being. Research in Canada has shown that sense of
      belonging has increased in recent years although important variations exist
      between regions and among certain ethnic groups. METHODS: The objective of this
      paper is to examine differences in sense of belonging to local community between
      Canadian-born and immigrant residents in three small-to-medium sized urban areas
      using primary data collected in: 1) Charlottetown, PEI; 2) Hamilton, Ontario, and
      3) Saskatoon, Saskatchewan. A mixed method approach is used in the analysis.
      First, a household telephone survey (n = 1529) asked respondents to rate their
      sense of belonging. This data was analyzed by way of summary statistics and
      ordered logistic regression. Second, a series of focus groups with immigrants in
      the three cities included questions on belonging and well-being (n = 11).
      RESULTS: The research found that sense of belonging is very high in the overall
      sample and in the three study sites, particularly in Charlottetown, and that
      there are no significant differences in levels of belonging between Canadian-born
      and immigrant respondents. However, among immigrants, sense of belonging was
      significantly lower for those living in Canada for 5 years or less. Consistent
      with the literature, positive mental health was found to be strongly associated
      with a positive sense of belonging for both Canadian-born and immigrant
      respondents. For immigrants, positive sense of belonging was associated with full
      time work and home-ownership, two factors not associated with the Canadian-born
      population. The paper also revealed that immigrants placed greater importance on
      knowing their neighbours on a first name basis and generally trusting people as
      determinants of a positive sense of belonging. Finally, the focus groups revealed
      that in addition to displaying a sense of belonging to their city of residence,
      immigrants also maintain strong feelings of belonging to their ethnic group.
      CONCLUSIONS: The paper concludes by offering several public health
      recommendations on how belonging can be enhanced among recent immigrants in
      smaller Canadian cities; these include improved coordination of services in order
      to contribute to a less overwhelming settlement process for immigrants.

PMID- 26289921
TI  - Capsule Commentary on Zallman et al., Unauthorized Immigrants Prolong the Life of
      Medicare's Trust Fund.

PMID- 26289919
TI  - Reconsolidation of a cocaine associated memory requires DNA methyltransferase
      activity in the basolateral amygdala.
AB  - Drug addiction is considered an aberrant form of learning, and drug-associated
      memories evoked by the presence of associated stimuli (drug context or drug
      related cues) contribute to recurrent craving and reinstatement. Epigenetic
      changes mediated by DNA methyltransferase (DNMT) have been implicated in the
      reconsolidation of fear memory. Here, we investigated the role of DNMT activity
      in the reconsolidation of cocaine-associated memories. Rats were trained over 10
      days to intravenously self-administer cocaine by nosepokes. Each injection was
      paired with a light/tone conditioned stimulus (CS). After acquisition of stable
      self-administration behaviour, rats underwent nosepoke extinction (10 d) followed
      by cue-induced reactivation and subsequent cue-induced and cocaine-priming + cue
      induced reinstatement tests or subsequently tested to assess the strength of the
      cocaine-associated cue as a conditioned reinforcer to drive cocaine seeking
      behaviour. Bilateral intra-basolateral amygdala (BLA) infusion of the DNMT
      inhibitor5-azacytidine (5-AZA, 1 MUg per side) immediately following reactivation
      decreased subsequent reinstatement induced by cues or cocaine priming as well as
      cue-maintained cocaine-seeking behaviour. In contrast, delayed intra-BLA infusion
      of 5-AZA 6 h after reactivation or 5-AZA infusion without reactivation had no
      effect on subsequent cue-induced reinstatement. These findings indicate that
      memory reconsolidation for a cocaine-paired stimulus depends critically on DNMT
      activity in the BLA. 

PMID- 26289922
TI  - The Veterans Choice Act and Dual Health System Use.

PMID- 26289923
TI  - Ebola Risk and Preparedness: A National Survey of Internists.
AB  - BACKGROUND: The 2014-2015 Ebola virus disease (Ebola) epidemic centered in West
      Africa highlighted recurring challenges in the United States regarding risk
      communication and preparedness during global epidemics. OBJECTIVE: To investigate
      perceptions, preparedness, and knowledge among U.S. internists with regard to
      Ebola risk. DESIGN: Cross-sectional Web-based national survey distributed by e
      mail between December 2014 and January 2015. PARTICIPANTS: Practicing U.S.
      internists participating in a research panel representative of American College
      of Physicians (ACP) membership. MAIN MEASURES: Respondents' perceptions of Ebola,
      reported sources of information, and reported management of possible Ebola cases.
      The primary predictor was the possibility of encountering Ebola (based on
      respondents' geographic proximity to designated airports or confirmed Ebola
      cases, or on their patients' travel histories). Pre-specified outcomes included
      reported management intensity in clinical vignettes involving patients at low
      risk of symptomatic Ebola as well as reported Ebola preparedness. KEY RESULTS:
      The survey response rate was 46.1 %. Among the 202 respondents, 9.9 % (95 % CI
      6.2-14.9 %) reported that they had recently evaluated a patient who had traveled
      to West Africa. Seventy percent (95 % CI 63.0-76.0 %) reported a practice-level
      protocol. The Centers for Disease Control and Prevention (CDC) was the most
      popular source for Ebola information (75.2 %, 95 % CI 68.7-81.0 %). Most
      respondents felt very (45.0 %) or somewhat prepared (52.0 %) to communicate
      information about or diagnose Ebola, especially those with the possibility of
      encountering Ebola and those who reported medical journals, professional groups,
      or government as information sources. One-fifth of respondents (19.8 %, 95 % CI
      14.5-26.0 %) reported overly intensive management for low-risk patients. Those
      with the possibility of encountering Ebola were less likely to report overly
      intensive management (3.1 vs. 22.9 %, p = 0.011). CONCLUSIONS: Internists had
      wide-ranging views and understanding of Ebola risk; those least likely to
      encounter Ebola were most likely to be overly aggressive in managing patients at
      low risk. Our findings underscore the need for better risk communication through
      various information channels to empower frontline providers in infectious disease
      outbreaks.

PMID- 26289924
TI  - Stop smoking services must become "e-cigarette" friendly, says Public Health
      England.

PMID- 26289925
TI  - Dynamic scalp topography reveals neural signs just before performance errors.
AB  - Performance errors may cause serious consequences. It has been reported that
      ongoing activity of the frontal control regions across trials associates with the
      occurrence of performance errors. However, neural mechanisms that cause
      performance errors remain largely unknown. In this study, we hypothesized that
      some neural functions required for correct outcomes are lacking just before
      performance errors, and to determine this lack of neural function we applied a
      spatiotemporal analysis to high-density electroencephalogram signals recorded
      during a visual discrimination task, a d2 test of attention. To our knowledge,
      this is the first report of a difference in the temporal development of scalp ERP
      between trials with error, and correct outcomes as seen by topography during the
      d2 test of attention. We observed differences in the signal potential in the
      frontal region and then the occipital region between reaction times matched with
      correct and error outcomes. Our observations suggest that lapses of top-down
      signals from frontal control regions cause performance errors just after the
      lapses. 

PMID- 26289926
TI  - Multiple physical signs detection and decision support system for hospitalized
      older adults.
AB  - Health monitoring systems have rapidly evolved during the past two decades and
      have the potential to change the way healthcare is currently delivered. Smart
      monitoring systems automate patient monitoring tasks and thereby improve patient
      workflow management. Moreover, expert systems have the potential to assist
      clinicians and improve their performance by accurately executing repetitive
      tasks, to which humans are ill-suited. Clinicians working in hospital wards are
      responsible for conducting a multitude of tasks which require constant vigilance,
      and thus the need for a smart decision support system has arisen. In particular,
      wireless patient monitoring systems are emerging as a low cost, reliable and
      accurate means of healthcare delivery. Vital signs monitoring systems are rapidly
      becoming part of today's healthcare delivery. The paradigm has shifted from
      traditional and manual recording to computer-based electronic records and,
      further, to handheld devices as versatile and innovative healthcare monitoring
      systems. The current study focuses on interpreting multiple physical signs and
      early warning for hospitalized older adults so that severe consequences can be
      minimized. Data from a total of 30 patients have been collated in New Zealand
      hospitals under local and national ethics approvals. The system records blood
      pressure, heart rate (pulse), oxygen saturation (SpO2), ear temperature and blood
      glucose levels from hospitalized patients and transfers this information to a web
      based software application for remote monitoring and further interpretation.
      Ultimately, this system is aimed to achieve a high level of agreement with
      clinicians' interpretation when assessing specific physical signs such as
      bradycardia, tachycardia, hypertension, hypotension, hypoxaemia, fever and
      hypothermia to generate early warnings. The performance of the vital signs
      interpretation system was validated through off-line as well as real-time tests
      with a high level of agreement between the system and physician.

PMID- 26289927
TI  - Routine use of array comparative genomic hybridization (aCGH) as standard
      approach for prenatal diagnosis of chromosomal abnormalities. Clinical experience
      of 1763 prenatal cases.
AB  - OBJECTIVE: This study aims to evaluate the diagnostic yield of comparative
      genomic hybridization microarrays (aCGH) and compare it with conventional
      karyotype analysis of standard >5-Mb resolution. METHOD: A total of 1763 prenatal
      samples were analyzed by aCGH (CytoChip Focus Constitutional microarrays,
      BlueGnome, Cambridge). The diagnostic yield of chromosomal abnormalities detected
      by aCGH was assessed, compared with conventional karyotype analysis. RESULTS: The
      result was pathogenic/unknown penetrance in 125 cases (7.1%), and a variant of
      unknown significance (VOUS) was detected in 13 cases (0.7%). Out of the 125 cases
      with abnormal findings, 110 were also detected by conventional karyotype
      analysis. The aCGH increment in diagnostic yield was 0.9% (15/1763) and 1.6% when
      VOUS were included. Stratifying the sample according to indications for prenatal
      invasive testing, the highest values of diagnostic yield increment were observed
      for patients positive for second-trimester sonographic markers (1.5%) and for the
      presence of fetal structural anomalies (1.3%). In contrast, the incremental yield
      was marginal in patients with fetus with increased nuchal translucency (0.5%).
      CONCLUSION: The present study indicates that routine implementation of aCGH
      offers an incremental yield over conventional karyotype analysis, which is also
      present in cases with 'milder' indications, further supporting its use as a first
      tier test.

PMID- 26289928
TI  - Clinical trials update from the European Society of Cardiology-Heart Failure
      meeting 2015: AUGMENT-HF, TITRATION, STOP-HF, HARMONIZE, LION HEART, MOOD-HF, and
      renin-angiotensin inhibitors in patients with heart and renal failure.
AB  - This article provides an overview on the key trials relevant to the
      pathophysiology, prevention, and treatment of heart failure (HF) presented at the
      Heart Failure Association (HFA) of the European Society of Cardiology (ESC)
      annual meeting held in Seville, Spain in May 2015. Trials reported include
      AUGMENT-AF (myocardial injections of calcium-alginate hydrogel), a propensity
      score-matched study of renin-angiotensin system antagonists in patients with HF
      and severe renal dysfunction, HARMONIZE (sodium zirconium cyclosilicate used to
      bind potassium), TITRATION, comparing two regimes for introducing LCZ696, STOP
      HF, a trial of intramyocardial stromal cell-derived factor-1, MOOD-HF
      (escitalopram for patients with heart failure and depression), and LION HEART, a
      trial of intermittent levosimendan therapy. Unpublished reports should be
      considered as preliminary, since analyses may change in the final publication. 

PMID- 26289929
TI  - Characterization and Functional Identification of a Gene Encoding Geranylgeranyl
      Diphosphate Synthase from Dunaliella bardawil.
AB  - Geranylgeranyl diphosphate synthase (GGPS) catalyzes the biosynthesis of
      geranylgeranyl diphosphate, a key precursor for carotenoid biosynthesis. In this
      study, a full-length cDNA encoding GGPS from Dunaliella bardawil (DbGGPS) was
      isolated by rapid amplification of cDNA ends (RACE) for the first time. The full
      length cDNA of DbGGPS was 1814 bp, containing a 1074 bp ORF encoding 357 amino
      acids with a calculated mass of 38.88 kDa. Analysis of DbGGPS genomic DNA
      revealed that it contained 10 exons and 9 introns. It was predicted that DbGGPS
      possessed a 48 amino acid transit peptide at its N terminus. Bioinformatic
      analysis revealed that DbGGPS was a member of a group of polyprenyltransferases
      with five conserved domains and two highly conserved aspartate-rich motifs. Using
      heterologous expression, carotenoid complementation assay, and gene deletion
      analysis, it was shown that the coding region of DbGGPS encodes a functional
      GGPS. This provides new gene sources for carotenoid genetic engineering. 

PMID- 26289930
TI  - Investigation of Methacrylic Acid at High Pressure Using Neutron Diffraction.
AB  - This article shows that pressure can be a low-intensity route to the synthesis of
      polymethacrylic acid. The exploration of perdeuterated methacrylic acid at high
      pressure using neutron diffraction reveals that methacrylic acid exhibits two
      polymorphic phase transformations at relatively low pressures. The first is
      observed at 0.39 GPa, where both phases were observed simultaneously and confirm
      our previous observations. This transition is followed by a second transition at
      1.2 GPa to a new polymorph that is characterized for the first time. On
      increasing pressure, the diffraction pattern of phase III deteriorates
      significantly. On decompression phase III persists to 0.54 GPa before
      transformation to the ambient pressure phase. There is significant loss of signal
      after decompression, signifying that there has been a loss of material through
      polymerization. The orientation of the molecules in phase III provides insight
      into the possible polymerization reaction. 

PMID- 26289932
TI  - A new captorhinid reptile from the Lower Permian of Oklahoma showing remarkable
      dental and mandibular convergence with microsaurian tetrapods.
AB  - The Lower Permian fossiliferous infills of the Dolese Brothers Limestone Quarry,
      near Richards Spur, Oklahoma, have preserved the most diverse assemblage of
      Paleozoic terrestrial vertebrates, including small-bodied reptiles and
      lepospondyl anamniotes. Many of these taxa were previously known only from
      fragmentary remains, predominantly dentigerous jaw elements and numerous isolated
      skeletal elements. The recent discovery of articulated skulls and skeletons of
      small reptiles permits the recognition that dentigerous elements, previously
      assigned at this locality to the anamniote lepospondyl Euryodus primus, belong to
      a new captorhinid eureptile, Opisthodontosaurus carrolli gen. et sp. nov. This
      mistaken identity points to a dramatic level of convergence in mandibular and
      dental anatomy in two distantly related and disparate clades of terrestrial
      tetrapods and sheds light on the earliest instance of durophagy in eureptiles.

PMID- 26289931
TI  - Re-exposure to beta cell autoantigens in pancreatic allograft recipients with
      preexisting beta cell autoantibodies.
AB  - Re-exposure to beta cell autoantigens and its relevance in the presence of donor
      specific antibodies (DSA) in pancreatic allograft recipients is not well known.
      Thirty-three patients requiring a pancreas transplant were enrolled in an IRB
      approved study. They underwent prospective monitoring for DSA and beta cell
      autoantibody (BCAA) levels to GAD65, insulinoma-associated antigen 2 (IA-2),
      insulin (micro-IAA [mIAA]), and islet-specific zinc transporter isoform-8 (ZnT8).
      Twenty-five (75.7%) had pre-transplant BCAA. Twenty had a single antibody (mIAA n
      = 15, GAD65 n = 5); five had two or more BCAA (GAD65 + mIAA n = 2, GAD65 +
      mIAA+IA-2 n = 2, GA65 + mIAA+IA-2 + ZnT8 = 1). No changes in GAD65 (p > 0.29), IA
      2 (>0.16), and ZnT8 (p > 0.07) were observed between pre-transplant and post
      transplant at 6 or 12 months. A decrease in mIAA from pre- to post-6 months (p <
      0.0001), 12 months (p < 0.0001), and from post-6 to post-12 months (p = 0.0002)
      was seen. No new BCAA was observed at one yr. Seven (21.0%) developed de novo
      DSA. The incidence of DSA was 24% in patients with BCAA vs. 25% in patients
      without BCAA (p = 0.69). Pancreatic allograft function of patients with vs.
      without BCAA, and with and without BCAA + DSA was comparable until last follow-up
      (three yr). Re-exposure to beta cell autoantigens by pancreas transplant may not
      lead to increased levels or development of new BCAA or pancreatic allograft
      dysfunction.

PMID- 26289933
TI  - Spatial distribution of an infectious disease in a small mammal community.
AB  - Chagas disease is a zoonosis caused by the parasite Trypanosoma cruzi and
      transmitted by insect vectors to several mammals, but little is known about its
      spatial epidemiology. We assessed the spatial distribution of T. cruzi infection
      in vectors and small mammals to test if mammal infection status is related to the
      proximity to vector colonies. During four consecutive years we captured and
      georeferenced the locations of mammal species and colonies of Mepraia spinolai, a
      restricted-movement vector. Infection status on mammals and vectors was evaluated
      by molecular techniques. To examine the effect of vector colonies on mammal
      infection status, we constructed an infection distance index using the distance
      between the location of each captured mammal to each vector colony and the
      average T. cruzi prevalence of each vector colony, weighted by the number of
      colonies assessed. We collected and evaluated T. cruzi infection in 944 mammals
      and 1976 M. spinolai. We found a significant effect of the infection distance
      index in explaining their infection status, when considering all mammal species
      together. By examining the most abundant species separately, we found this effect
      only for the diurnal and gregarious rodent Octodon degus. Spatially explicit
      models involving the prevalence and location of infected vectors and hosts had
      not been reported previously for a wild disease.

PMID- 26289934
TI  - Immunohistochemical analysis of extramammary Paget's disease with Bowenoid
      features: case report and review of the literature.

PMID- 26289935
TI  - High rates of fatigue and sleep disturbances in dystonia.
AB  - BACKGROUND: Nonmotor symptoms in dystonia are increasingly recognized to impair
      the quality of life. The primary objective of this study was to determine the
      prevalence of fatigue and sleep disturbances in dystonia and to ascertain their
      impact on quality of life using standardized questionnaires. METHODS: Dystonia
      patients presenting to a Botulinum toxin clinic were prospectively administered
      Fatigue Severity Scale (FSS), Multidimensional Fatigue Inventory (MFI), Epworth
      Sleepiness Scale (ESS) and Parkinson's Disease Sleep Scale (PDSS) for assessment
      of fatigue and sleep disturbances. Health-related Quality of life (HRQOL) was
      determined using MOS SF-36 scale and depressive symptoms were assessed using the
      Beck Depression Inventory II. RESULTS: Ninety-one patients with dystonia
      participated (66 women, 25 men, mean age 60 +/- 17 years). Nine subjects had
      generalized dystonia, 18 segmental dystonia and 64 had focal dystonia. Moderate
      to severe fatigue was present in 43% of the cohort (FSS), excessive daytime
      somnolence in 27% (ESS) and other sleep disturbances in 26% (PDSS). FSS and MFI
      scores correlated significantly with HRQOL even when controlled for depression
      and sleep disturbances. Excessive daytime somnolence and nocturnal sleep
      disturbances correlated significantly with the HRQOL; however, these effects were
      not seen for daytime somnolence when controlled for depression. Psychometric
      testing found adequate reliabilities and convergent validities for both fatigue
      and sleep scales. CONCLUSION: Fatigue and sleep disturbances revealed high
      prevalence rates in this large, first of its dystonia study. They negatively
      impacted the quality of life even when controlled for comorbid depression.

PMID- 26289936
TI  - Diagnostic accuracy of different body weight and height-based definitions of
      childhood obesity in identifying overfat among Chinese children and adolescents:
      a cross-sectional study.
AB  - BACKGROUND: Various body weight and height-based references are used to define
      obese children and adolescents. However, no study investigating the diagnostic
      accuracies of the definitions of obesity and overweight in Hong Kong Chinese
      children and adolescents has been conducted. The current study aims to
      investigate the diagnostic accuracy of BMI-based definitions and 1993 HK
      reference in screening excess body fat among Hong Kong Chinese children and
      adolescents. METHODS: A total of 2,134 participants (1,135 boys and 999 girls)
      were recruited from local schools. The foot-to-foot BIA scale was applied to
      assess %BF using standard methods. The criterion of childhood obesity (i.e.,
      overfat) was defined as over 25 %BF for boys and over 30 %BF for girls. Childhood
      obesity was also determined from four BMI-based references and the 1993 HK
      reference. The diagnostic accuracy of these existing definitions for childhood
      obesity in screening excess body fat was evaluated using diagnostic indices.
      RESULTS: Overall, %BF was significantly correlated with anthropometry
      measurements in both genders (in boys, r = 0.747 for BMI 0.766 for PWH; in girls,
      r = 0.930 for BMI 0.851 for PWH). The prevalence rates of overweight and obesity
      determined by BMI-based references were similar with the prevalence rates of
      obesity in the 1993 HK reference in both genders. All definitions for childhood
      obesity showed low sensitivity (in boys, 0.325-0.761; in girls, 0.128-0.588) in
      detecting overfat. Specificities were high for cut-offs among all definitions for
      childhood obesity (in boys, 0.862-0.980; in girls, 0.973-0.998). CONCLUSIONS: In
      conclusion, prevalence rates of childhood obesity or overweight varied widely
      according to the diagnostic references applied. The diagnostic performance for
      weight and height-based references for obesity is poorer than expected for both
      genders among Hong Kong Chinese children and adolescents. In order to improve the
      diagnosis accuracy of childhood obesity, either cut-off values of body weight and
      height-based definitions of childhood obesity should be revised to increase the
      sensitivity or the possibility of using other indirect methods of estimating the
      %BF should be explored.

PMID- 26289937
TI  - High incidence of diagnosis with syphilis co-infection among men who have sex
      with men in an HIV cohort in Ontario, Canada.
AB  - BACKGROUND: The re-emergence of syphilis among HIV-positive gay and other men who
      have sex with men (MSM) requires vigilance. We estimated incidence of and risk
      factors for first and subsequent syphilis diagnoses among MSM in HIV care in
      Ontario, Canada. METHODS: We analyzed data from 2,280 MSM under follow-up from
      2006 to 2010 in the Ontario HIV Treatment Network Cohort Study (OCS), a multi
      site clinical cohort. We obtained syphilis serology results via record linkage
      with the provincial public health laboratory. Rates were calculated using Poisson
      regression. RESULTS: First syphilis diagnoses occurred at a rate of 2.0 per 100
      person-years (95 % CI 1.7, 2.4; 121 cases) whereas the re-diagnosis rate was 7.5
      per 100 person-years (95 % CI 6.3, 8.8; 136 cases). We observed higher rates over
      time and among men who were aged <30 years, receiving care in the two largest
      urban centers, or had a previous syphilis diagnosis. Syphilis diagnosis was less
      common among Indigenous men, men with higher CD4 cell counts, and, for first
      diagnoses only, among men with less than high school education. CONCLUSIONS:
      Compared to reported cases in the general male population, incidence of a new
      syphilis diagnosis was over 300 times greater among HIV-positive MSM but year-to
      year changes reflected provincial trends. Re-diagnosis was common, suggesting
      treatment failure or re-infection. Novel syphilis control efforts are needed
      among HIV-positive MSM.

PMID- 26289938
TI  - Association of CD40 polymorphisms and haplotype with risk of systemic lupus
      erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that is
      caused by genetic and environmental factors. Current evidence shows that the CD40
      CD40L system plays a crucial role in the development, progression and outcome of
      SLE. CD40, which stimulates lymphocyte proliferation and differentiation, is an
      important immunomodulator and is expressed in the thyroid follicular cells as
      well as antigen-presenting cells. The aim of the present study was to investigate
      whether CD40 gene polymorphism confers susceptibility to SLE and its impact on
      CD40 expression in Chinese. We analyzed four single nucleotide polymorphisms of
      CD40 gene rs1883832C/T, rs13040307C/T, rs752118C/T, and rs3765459G/A in 205
      patients with SLE and 220 age- and sex-matched controls, using Snapshot SNP
      genotyping assays and DNA sequencing method. Soluble CD40 (sCD40) levels were
      measured by ELISA. There were significant differences in the genotype and allele
      frequencies of CD40 gene rs1883832 C/T polymorphism between the group of patients
      with SLE and the control group (P < 0.05). sCD40 levels were increased in
      patients with SLE compared with controls (P < 0.01). Moreover, genotypes carrying
      the CD40 rs1883832 T variant allele were associated with increased CD40 levels
      compared with the homozygous wild-type genotype in patients with SLE. The
      rs1883832 C/T polymorphism of CD40 and its sCD40 levels were associated with SLE
      in the Chinese population. These data suggest that CD40 gene may play an
      essential role in the development of SLE.

PMID- 26289939
TI  - Influence of biochar on sorption, leaching and dissipation of bisphenol A and
      17alpha-ethynylestradiol in soil.
AB  - Biochar, as a soil amendment, provided a very cost-effective, convenient route to
      dispose organic residues. In the present study, the impact of adding biochar on
      the sorption, leaching and dissipation processes of bisphenol A (BPA) and 17alpha
      ethynylestradiol (EE2) in soil was investigated. The biochar derived from corn
      stalks at 500  degrees C for 1.5 h was characterized by a highly aromatic and
      microporous structure with various functional groups on the surface. In the batch
      sorption studies, the application of 4 wt% biochar to soil significantly
      increased the solid-water distribution coefficients by 263% for BPA and by 298%
      for EE2 at the pollutant equilibrium concentration of 0.01 mg L(-1). In the
      leaching experiment, after five leaching periods, soil amended with 1 wt%, 2 wt%
      and 4 wt% biochar reduced the cumulative amount by 19%, 28% and 53% for BPA, 42%,
      58% and 77% for EE2 compared to the biochar-free soil. Interestingly, during the
      90 d incubation experiment, BPA and EE2 dissipations were not significantly
      affected by the added biochar, while remarkable decreases of CaCl2 extractable
      BPA and EE2 were observed. The overall results highlighted the distinctive
      potential of this biochar in reducing the mobility of BPA and EE2 in soil,
      meanwhile without attenuating the degradation of the two pollutants. 

PMID- 26289940
TI  - Use of semantic workflows to enhance transparency and reproducibility in clinical
      omics.
AB  - BACKGROUND: Recent highly publicized cases of premature patient assignment into
      clinical trials, resulting from non-reproducible omics analyses, have prompted
      many to call for a more thorough examination of translational omics and
      highlighted the critical need for transparency and reproducibility to ensure
      patient safety. The use of workflow platforms such as Galaxy and Taverna have
      greatly enhanced the use, transparency and reproducibility of omics analysis
      pipelines in the research domain and would be an invaluable tool in a clinical
      setting. However, the use of these workflow platforms requires deep domain
      expertise that, particularly within the multi-disciplinary fields of
      translational and clinical omics, may not always be present in a clinical
      setting. This lack of domain expertise may put patient safety at risk and make
      these workflow platforms difficult to operationalize in a clinical setting. In
      contrast, semantic workflows are a different class of workflow platform where
      resultant workflow runs are transparent, reproducible, and semantically
      validated. Through semantic enforcement of all datasets, analyses and user
      defined rules/constraints, users are guided through each workflow run, enhancing
      analytical validity and patient safety. METHODS: To evaluate the effectiveness of
      semantic workflows within translational and clinical omics, we have implemented a
      clinical omics pipeline for annotating DNA sequence variants identified through
      next generation sequencing using the Workflow Instance Generation and
      Specialization (WINGS) semantic workflow platform. RESULTS: We found that the
      implementation and execution of our clinical omics pipeline in a semantic
      workflow helped us to meet the requirements for enhanced transparency,
      reproducibility and analytical validity recommended for clinical omics. We
      further found that many features of the WINGS platform were particularly primed
      to help support the critical needs of clinical omics analyses. CONCLUSIONS: This
      is the first implementation and execution of a clinical omics pipeline using
      semantic workflows. Evaluation of this implementation provides guidance for their
      use in both translational and clinical settings.

PMID- 26289941
TI  - In Vivo Evaluation of Wearable Head Impact Sensors.
AB  - Inertial sensors are commonly used to measure human head motion. Some sensors
      have been tested with dummy or cadaver experiments with mixed results, and
      methods to evaluate sensors in vivo are lacking. Here we present an in vivo
      method using high speed video to test teeth-mounted (mouthguard), soft tissue
      mounted (skin patch), and headgear-mounted (skull cap) sensors during 6-13 g
      sagittal soccer head impacts. Sensor coupling to the skull was quantified by
      displacement from an ear-canal reference. Mouthguard displacements were within
      video measurement error (<1 mm), while the skin patch and skull cap displaced up
      to 4 and 13 mm from the ear-canal reference, respectively. We used the
      mouthguard, which had the least displacement from skull, as the reference to
      assess 6-degree-of-freedom skin patch and skull cap measurements. Linear and
      rotational acceleration magnitudes were over-predicted by both the skin patch
      (with 120% NRMS error for a(mag), 290% for alpha(mag)) and the skull cap (320%
      NRMS error for a(mag), 500% for alpha(mag)). Such over-predictions were largely
      due to out-of-plane motion. To model sensor error, we found that in-plane skin
      patch linear acceleration in the anterior-posterior direction could be modeled by
      an underdamped viscoelastic system. In summary, the mouthguard showed tighter
      skull coupling than the other sensor mounting approaches. Furthermore, the in
      vivo methods presented are valuable for investigating skull acceleration sensor
      technologies.

PMID- 26289942
TI  - Inkjet-Print Micromagnet Array on Glass Slides for Immunomagnetic Enrichment of
      Circulating Tumor Cells.
AB  - We report an inkjet-printed microscale magnetic structure that can be integrated
      on regular glass slides for the immunomagnetic screening of rare circulating
      tumor cells (CTCs). CTCs detach from the primary tumor site, circulate with the
      bloodstream, and initiate the cancer metastasis process. Therefore, a liquid
      biopsy in the form of capturing and analyzing CTCs may provide key information
      for cancer prognosis and diagnosis. Inkjet printing technology provides a non
      contact, layer-by-layer and mask-less approach to deposit defined magnetic
      patterns on an arbitrary substrate. Such thin film patterns, when placed in an
      external magnetic field, significantly enhance the attractive force in the near
      field close to the CTCs to facilitate the separation. We demonstrated the
      efficacy of the inkjet-print micromagnet array integrated immunomagnetic assay in
      separating COLO205 (human colorectal cancer cell line) from whole blood samples.
      The micromagnets increased the capture efficiency by 26% compared with using
      plain glass slide as the substrate. 

PMID- 26289944
TI  - Transcriptional regulation of Annexin A2 promotes starvation-induced autophagy.
AB  - Autophagy is an important degradation pathway, which is induced after starvation,
      where it buffers nutrient deprivation by recycling macromolecules in organisms
      from yeast to man. While the classical pathway mediating this response is via
      mTOR inhibition, there are likely to be additional pathways that support the
      process. Here, we identify Annexin A2 as an autophagy modulator that regulates
      autophagosome formation by enabling appropriate ATG9A trafficking from endosomes
      to autophagosomes via actin. This process is dependent on the Annexin A2
      effectors ARP2 and Spire1. Annexin A2 expression increases after starvation in
      cells in an mTOR-independent fashion. This is mediated via Jun N-terminal kinase
      activation of c-Jun, which, in turn, enhances the trans-activation of the Annexin
      A2 promoter. Annexin A2 knockdown abrogates starvation-induced autophagy, while
      its overexpression induces autophagy. Hence, c-Jun-mediated transcriptional
      responses support starvation-induced autophagy by regulating Annexin A2
      expression levels. 

PMID- 26289946
TI  - Reconstruction of full high-resolution HSQC using signal split in aliased
      spectra.
AB  - Resolution enhancement is a long-sought goal in NMR spectroscopy. In conventional
      multidimensional NMR experiments, such as the (1) H-(13) C HSQC, the resolution
      in the indirect dimensions is typically 100 times lower as in 1D spectra because
      it is limited by the experimental time. Reducing the spectral window can
      significantly increase the resolution but at the cost of ambiguities in
      frequencies as a result of spectral aliasing. Fortunately, this information is
      not completely lost and can be retrieved using methods in which chemical shifts
      are encoded in the aliased spectra and decoded after processing to reconstruct
      high-resolution (1) H-(13) C HSQC spectrum with full spectral width and a
      resolution similar to that of 1D spectra. We applied a new reconstruction method,
      RHUMBA (reconstruction of high-resolution using multiplet built on aliased
      spectra), to spectra obtained from the differential evolution for non-ambiguous
      aliasing-HSQC and the new AMNA (additional modulation for non-ambiguous aliasing)
      HSQC experiments. The reconstructed spectra significantly facilitate both manual
      and automated spectral analyses and structure elucidation based on heteronuclear
      2D experiments. The resolution is enhanced by two orders of magnitudes without
      the usual complications due to spectral aliasing.

PMID- 26289945
TI  - The effects of single nucleotide polymorphisms in glutamatergic neurotransmission
      genes on neural response to alcohol cues and craving.
AB  - The aim of the current study was to determine genotype effects of four single
      nucleotide polymorphisms (SNPs) in the genes of the N-Methyl-d-aspartate receptor
      (GRIN1, GRIN2A, GRIN2C) and kainate receptor (GRIK1), which have been previously
      associated with alcoholism, on behavior, neural cue-reactivity and drinking
      outcome. Eighty-six abstinent alcohol dependent patients were recruited from an
      in-patient setting. Neuropsychological tests, genotyping and functional magnetic
      resonance imaging (fMRI) were used to study genotype effects. GRIN2C risk allele
      carriers displayed increased alcohol cue-induced activation in the anterior
      cingulate cortex (ACC) and dorsolateral prefrontal cortex (dlPFC). Neural
      activation in the ACC positively correlated with craving for alcohol (r = 0.201,
      P = 0.032), whereas activation in the dlPFC showed a negative association (r = 
      0.215, P = 0.023). In addition, dlPFC activation predicted time to first relapse
      (HR = 2.701, 95%CI 1.244-5.864, P = 0.012). GRIK1 risk allele carriers showed
      increased cue-induced activation in the medial prefrontal (PFC) and orbitofrontal
      cortex (OFC) and in the lateral PFC and OFC. Activation in both clusters
      positively correlated with alcohol craving (rmedOFC, medPFC  = 0.403, P = 0.001,
      rlatOFC, latPFC  = 0.282, P = 0.008), and activation in the cluster that
      encompassed the medial OFC predicted time to first relapse (HR = 1.911, 95%CI
      1.030-3.545, P = 0.040). Findings indicate that SNPs in the GRIN2C and GRIK1
      genes are associated with altered cue-induced brain activation that is related to
      craving for alcohol and relapse risk. 

PMID- 26289943
TI  - Characterization and comparative profiling of the small RNA transcriptomes in two
      phases of flowering in Cymbidium ensifolium.
AB  - BACKGROUND: Cymbidium ensifolium is one of the most important ornamental flowers
      in China, with an elegant shape, beautiful appearance, and a fragrant aroma. Its
      unique flower shape has long attracted scientists. MicroRNAs (miRNAs) are
      critical regulators in plant development and physiology, including floral
      development. However, to date, few studies have examined miRNAs in C. ensifolium.
      RESULTS: In this study, we employed Solexa technology to sequence four small RNA
      libraries from two flowering phases to identify miRNAs related to floral
      development. We identified 48 mature conserved miRNA and 71 precursors. These
      conserved miRNA belonged to 20 families. We also identified 45 novel miRNA which
      includes 21 putative novel miRNAs*, and 28 hairpin forming precursors. Two trans
      acting small interfering RNAs (ta-siRNAs) were identified, one of which was
      homologous to TAS3a1. TAS3a1 belongs to the TAS3 family, which has been
      previously reported to target auxin response factors (ARF) and be involved in
      plant growth and floral development. Moreover, we built a C. ensifolium
      transctriptome database to identify genes targeted by miRNA, which resulted in
      790 transcriptomic target unigenes. The target unigenes were annotated with
      information from the non-redundant (Nr), gene ontology database (GO), eukaryotic
      orthologous groups (KOGs) and Kyoto encyclopedia of genes and genomes (KEGG)
      database. The unigenes included MADS-box transcription factors targeted by
      miR156, miR172 and miR5179, and various hormone responding factors targeted by
      miR159. The MADS-box transcription factors are well known to determine the
      identity of flower organs and hormone responding factors involved in floral
      development. In expression analysis, three novel and four conserved miRNA were
      differentially expressed between two phases of flowering. The results were
      confirmed by RNA-seq and qRT-PCR. The differential expression of two miRNA,
      miR160 and miR396, targeted ARFs and growth regulating factor (GRF),
      respectively. However, most of these small RNA were clustered in the
      uncharacterized group, which suggests there may be many novel small non-coding
      RNAs yet to be discovered. CONCLUSION: Our study provides a diverse set of miRNAs
      related to cymbidium floral development and serves as a useful resource for
      investigating miRNA-mediated regulatory mechanisms of floral development.

PMID- 26289948
TI  - Hybrid PVDF/PVDF-graft-PEGMA Membranes for Improved Interface Strength and
      Lifetime of PEDOT:PSS/PVDF/Ionic Liquid Actuators.
AB  - The exploitation of soft conducting polymer-based actuators suffers from two main
      shortcomings: their short life cycle and the reproducibility of the fabrication
      techniques. The short life cycle usually results from the delamination of the
      components due to stresses at the interface during the actuation. In this work,
      to achieve strong adhesion to poly(3,4- ethylenedioxythiophene)
      poly(styrenesulfonate) ( PEDOT: PSS) electrodes, the wetting properties of the
      surface of a polyvinylidene fluoride (PVDF) membrane are improved using argon
      plasma-induced surface polymerization of poly(ethylene glycol) monomethyl ether
      methacrylate (PEGMA). Hybrid membranes are created with hydrophilic PVDF-graft
      PEGMA outer surfaces and hydrophobic bulk. The width of each layer is controlled
      by spray coating, as it allows for the deposition of the reaction precursor to a
      certain depth. Subsequently, a PEDOT: PSS water solution fills the pores of the
      functionalized part of the membrane and a mixing layer between PEDOT: PSS and
      PVDF is created. We also show that PVDF-graft-PEGMA copolymers play an important
      role in binding the membrane to the electrodes and that direct mechanical
      interlocking in the pores can further improve the adhesion. Finally, PEDOT:
      PSS/PVDF-graft-PEGMA/PEDOT:PSS actuators are made by simple solution casting.
      They are capable of producing high strains of 0.6% and show no signs of
      delamination after more than 150 h or 10(4) actuation cycles. Furthermore, the
      preservation of the hydrophobic membrane in between two PEDOT: PSS layers
      increases the resistance between them from 0.36 Omega to 0.16 MOmega, thus
      drastically modifying the power dissipation of the actuators.

PMID- 26289947
TI  - The Impending Dilemma of Electrocardiogram Screening in Athletic Children.
AB  - Sudden cardiac death (SCD) affects 2/100,000 young, active athletes per year of
      which 40% are less than 18 years old. In 2004, the International Olympic
      Committee accepted the Lausanne Recommendations, including a 12-lead
      electrocardiogram (ECG), as a pre-participation screening tool for adult Olympic
      athletes. The debate on extending those recommendations to the pediatric
      population has recently begun. The aims of our study were to highlight the
      characteristics of the young athlete ECG, phenotypical manifestations of SCD
      related disease in children, and challenges of implanting ECG screening in
      athletic children. A systematic review of the literature is performed. We
      searched available electronic medical databases for articles relevant to SCD,
      ECG, silent cardiac diseases, and athletic children. We focused on ECG screening
      and description in a pediatric population. We identified 2240 studies. Sixty-two
      relevant articles and one book were selected. In children, prepubertal ECG and
      the ECG phenotype of most SCD-related diseases differ notably from adults. The
      characteristics of the prepubertal ECG and of the phenotypical manifestation of
      SCD-related disease in children will result in less specific and less sensitive
      ECG-based screening programs. Those limitations advise against extending the
      adult recommendation to children, without further studies. Until then, history
      and physical exam should remain the cornerstone of screening for SCD-related
      pathologies in children.

PMID- 26289949
TI  - Effectiveness and safety of artemether-lumefantrine versus artesunate-amodiaquine
      for unsupervised treatment of uncomplicated falciparum malaria in patients of all
      age groups in Nanoro, Burkina Faso: a randomized open label trial.
AB  - BACKGROUND: Several studies have reported high efficacy and safety of artemisinin
      based combination therapy (ACT) mostly under strict supervision of drug intake
      and limited to children less than 5 years of age. Patients over 5 years of age
      are usually not involved in such studies. Thus, the findings do not fully reflect
      the reality in the field. This study aimed to assess the effectiveness and safety
      of ACT in routine treatment of uncomplicated malaria among patients of all age
      groups in Nanoro, Burkina Faso. METHODS: A randomized open label trial comparing
      artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) was carried out
      from September 2010 to October 2012 at two primary health centres (Nanoro and
      Nazoanga) of Nanoro health district. A total of 680 patients were randomized to
      receive either ASAQ or AL without any distinction by age. Drug intake was not
      supervised as pertains in routine practice in the field. Patients or their
      parents/guardians were advised on the time and mode of administration for the 3
      days treatment unobserved at home. Follow-up visits were performed on days 3, 7,
      14, 21, and 28 to evaluate clinical and parasitological resolution of their
      malaria episode as well as adverse events. PCR genotyping of merozoite surface
      proteins 1 and 2 (msp-1, msp-2) was used to differentiate recrudescence and new
      infection. RESULTS: By day 28, the PCR corrected adequate clinical and
      parasitological response was 84.1 and 77.8 % respectively for ASAQ and AL. The
      cure rate was higher in older patients than in children under 5 years old. The
      risk of re-infection by day 28 was higher in AL treated patients compared with
      those receiving ASAQ (p < 0.00001). Both AL and ASAQ treatments were well
      tolerated. CONCLUSION: This study shows a lowering of the efficacy when drug
      intake is not directly supervised. This is worrying as both rates are lower than
      the critical threshold of 90 % required by the WHO to recommend the use of an
      anti-malarial drug in a treatment policy. TRIAL REGISTRATION: NCT01232530.

PMID- 26289950
TI  - The effect on potential adverse drug events of a pharmacist-acquired medication
      history in an emergency department: a multicentre, double-blind, randomised,
      controlled, parallel-group study.
AB  - BACKGROUND: Potential adverse drug events (PADEs) are defined as being
      potentially harmful unintentional medication discrepancies. Discrepancies
      regarding medication history (MH) often occur when a patient is being admitted to
      a hospital's emergency department (ED); they are clinically important and
      represent a significant source of data regarding adverse drug events occurring
      during emergency admission to hospital. This study sought to measure the impact
      of pharmacist-acquired MH during admission to an ED; it focused on whether a
      patient's current home medication regimen being available for a doctor when
      consulting a patient in an ED would have reduced potential adverse drug events.
      METHOD: A multicentre, double-blind, randomised, controlled parallel-group study
      was carried out at 3 large teaching hospitals in Bogota, Colombia. Two hundred
      and seventy patients who had been admitted to an ED were enrolled; each had a
      standardised, comprehensive MH interview, focusing on a patient's current home
      medication regimen prior to being seen by a doctor. Data recorded on the
      admission medication order form was available to be used by a doctor during
      consultation in the ED. The main outcome dealt with comparing the intervention
      and control groups regarding the percentage of patients having at least 1
      potential adverse drug event. RESULTS: There were 811 PADE (3.35 per patient),
      528 (65%) on the standard care arm and 283 (35%) on an intervention arm. Most
      PADEs were judged to have had the potential to cause moderate discomfort (42.6%),
      33.4% were deemed unlikely to have caused harm and 23.9% were judged to have had
      the potential to cause clinical deterioration. CONCLUSION: Many patients suffer
      potentially adverse drugs events during the transition of care from home to a
      hospital. Patient safety-focused medication reconciliation during admission to an
      ED involving a pharmacist and drawing up a history of complete medication could
      contribute towards reducing the risk of PADES occurring and improve follow-up of
      patients' medication-based therapy. TRIAL REGISTRATION: 28/10/2012,
      ISRCTN63455839.

PMID- 26289951
TI  - "Discovery and development of new anticancer drugs inspired from natural product
      leads" part 2.

PMID- 26289953
TI  - JGV 96:6 June 2015.

PMID- 26289952
TI  - Emerging Infections Program--State Health Department Perspective.
AB  - The Emerging Infections Program (EIP) is a collaboration between the Centers for
      Disease Control and Prevention and 10 state health departments working with
      academic partners to conduct active population-based surveillance and special
      studies for several emerging infectious disease issues determined to need special
      attention. The Centers for Disease Control and Prevention funds the 10 EIP sites
      through cooperative agreements. Our objective was to highlight 1) what being an
      EIP site has meant for participating health departments and associated academic
      centers, including accomplishments and challenges, and 2) the synergy between the
      state and federal levels that has resulted from the collaborative relationship.
      Sharing these experiences should provide constructive insight to other public
      health programs and other countries contemplating a collaborative federal-local
      approach to collective public health challenges. 

PMID- 26289954
TI  - Axons to Exons: the Molecular Diagnosis of Rare Neurological Diseases by Next
      Generation Sequencing.
AB  - Neurological disorders secondary to single gene mutations are an extremely
      heterogeneous group of diseases, individually rare, and often associated with
      progressive and severe disability. Given the degree of both clinical and genetic
      heterogeneity, next-generation sequencing (NGS) has become an important
      diagnostic tool. Multi-gene panel testing based on NGS is now prominently used,
      while whole-exome sequencing and whole-genome sequencing are emerging to
      facilitate the molecular diagnosis for many genetic neurological diseases.
      Although single-gene testing remains an important first tier test for disorders
      with clear phenotype-genotype correlation, NGS provides an expanding unbiased
      approach to identify rare mutations in genes known to be associated with
      genetically heterogeneous diseases, and those not initially considered by the
      clinician due to rarity or atypical clinical presentation. Given the decreasing
      costs and relatively rapid time to results, NGS-based assessment is quickly
      becoming a standard-of-care test for patients with genetic neurological diseases.

PMID- 26289955
TI  - Effects of a wearable exoskeleton stride management assist system (SMA(r)) on
      spatiotemporal gait characteristics in individuals after stroke: a randomized
      controlled trial.
AB  - BACKGROUND: Robots offer an alternative, potentially advantageous method of
      providing repetitive, high-dosage, and high-intensity training to address the
      gait impairments caused by stroke. In this study, we compared the effects of the
      Stride Management Assist (SMA(r)) System, a new wearable robotic device developed
      by Honda R&D Corporation, Japan, with functional task specific training (FTST) on
      spatiotemporal gait parameters in stroke survivors. METHODS: A single blinded
      randomized control trial was performed to assess the effect of FTST and task
      specific walking training with the SMA(r) device on spatiotemporal gait
      parameters. Participants (n=50) were randomly assigned to FTST or SMA. Subjects
      in both groups received training 3 times per week for 6-8 weeks for a maximum of
      18 training sessions. The GAITRite(r) system was used to collect data on
      subjects' spatiotemporal gait characteristics before training (baseline), at mid
      training, post-training, and at a 3-month follow-up. RESULTS: After training,
      significant improvements in gait parameters were observed in both training groups
      compared to baseline, including an increase in velocity and cadence, a decrease
      in swing time on the impaired side, a decrease in double support time, an
      increase in stride length on impaired and non-impaired sides, and an increase in
      step length on impaired and non-impaired sides. No significant differences were
      observed between training groups; except for SMA group, step length on the
      impaired side increased significantly during self-selected walking speed trials
      and spatial asymmetry decreased significantly during fast-velocity walking
      trials. CONCLUSIONS: SMA and FTST interventions provided similar, significant
      improvements in spatiotemporal gait parameters; however, the SMA group showed
      additional improvements across more parameters at various time points. These
      results indicate that the SMA(r) device could be a useful therapeutic tool to
      improve spatiotemporal parameters and contribute to improved functional mobility
      in stroke survivors. Further research is needed to determine the feasibility of
      using this device in a home setting vs a clinic setting, and whether such home
      use provides continued benefits. TRIAL REGISTRATION: This study is registered
      under the title "Development of walk assist device to improve community
      ambulation" and can be located in clinicaltrials.gov with the study identifier:
      NCT01994395 .

PMID- 26289956
TI  - Preparation for global introduction of inactivated poliovirus vaccine: safety
      evidence from the US Vaccine Adverse Event Reporting System, 2000-12.
AB  - BACKGROUND: Safety data from countries with experience in the use of inactivated
      poliovirus vaccine (IPV) are important for the global polio eradication strategy
      to introduce IPV into the immunisation schedules of all countries. In the USA,
      IPV has been included in the routine immunisation schedule since 1997. We aimed
      to analyse adverse events after IPV administration reported to the US Vaccine
      Adverse Event Reporting System (VAERS). METHODS: We analysed all VAERS data
      associated with IPV submitted between Jan 1, 2000, and Dec 31, 2012, either as
      individual or as combination vaccines, for all age and sex groups. We analysed
      the number and event type (non-serious, non-fatal serious, and death reports) of
      individual reports, and explored the most commonly coded event terms to describe
      the adverse event. We classified death reports according to previously published
      body-system categories (respiratory, cardiovascular, neurological,
      gastrointestinal, other infectious, and other non-infectious) and reviewed death
      reports to identify the cause of death. We classified sudden infant death
      syndrome as a separate cause of death considering previous concerns about sudden
      infant syndrome after vaccines. We used empirical Bayesian data mining methods to
      identify disproportionate reporting of adverse events for IPV compared with other
      vaccines. Additional VAERS data from 1991 to 2000 were analysed to compare the
      safety profiles of IPV and oral poliovirus vaccine (OPV). FINDINGS: Of the 41,792
      adverse event reports submitted, 39,568 (95%) were for children younger than 7
      years. 38,381 of the reports for children in this age group (97%) were for
      simultaneous vaccination with IPV and other vaccines (most commonly pneumococcal
      and acellular pertussis vaccines), whereas standalone IPV vaccines accounted for
      0.5% of all reports. 34,880 reports were for non-serious events (88%), 3905
      reports were for non-fatal serious events (10%), and 783 reports were death
      reports (2%). Injection-site erythema was the most commonly coded term for non
      serious events (29%), and pyrexia for non-fatal serious events (38%). Most deaths
      (96%) were in children aged 12 months or younger; most (52%) had sudden infant
      death syndrome as the reported cause of death. The safely profiles of combined
      IPV and whole-cell pertussis vaccines, OPV and whole-cell pertussis vaccines, and
      OPV and acellular pertussis vaccines were similar. We noted no indication of
      disproportionate reporting of adverse events after immunisation with IPV
      containing vaccines compared with other vaccines between 1990 and 2013.
      INTERPRETATION: Fairly few adverse events were reported for the more than 250
      million IPV doses distributed between 2000 and 2012. Sudden infant death syndrome
      reports after IPV were consistent with reporting patterns for other vaccines. No
      new or unexpected vaccine safety problems were identified for fatal, non-fatal
      serious, and non-serious reports in this assessment of adverse events after IPV.
      FUNDING: None.

PMID- 26289957
TI  - Good news for billions of children who will receive IPV.

PMID- 26289958
TI  - Clinical significance of circulating vascular cell adhesion molecule-1 to white
      matter disintegrity in Alzheimer's dementia.
AB  - Endothelial dysfunction leads to worse cognitive performance in Alzheimer's
      dementia (AD). While both cerebrovascular risk factors and endothelial
      dysfunction lead to activation of vascular cell adhesion molecule-1 (VCAM-1),
      intercellular adhesion molecule-1 (ICAM-1) and E-selectin, it is not known
      whether these biomarkers extend the diagnostic repertoire in reflecting
      intracerebral structural damage or cognitive performance. A total of 110 AD
      patients and 50 age-matched controls were enrolled. Plasma levels of VCAM-1, ICAM
      1 and E-selectin were measured and correlated with the cognitive performance,
      white matter macro-structural changes, and major tract-specific fractional
      anisotropy quantification. The AD patients were further stratified by clinical
      dementia rating score (mild dementia, n=60; moderate-to-severe dementia, n=50).
      Compared with the controls, plasma levels of VCAM-1 (p< 0.001), ICAM-1 (p=0.028)
      and E-selectin (p=0.016) were significantly higher in the patients, but only VCAM
      1 levels significantly reflected the severity of dementia (p< 0.001). In
      addition, only VCAM-1 levels showed an association with macro- and micro- white
      matter changes especially in the superior longitudinal fasciculus (p< 0.001),
      posterior thalamic radiation (p=0.002), stria terminalis (p=0.002) and corpus
      callosum (p=0.009), and were independent of, age and cortical volume. These
      tracts show significant association with MMSE, short term memory and visuospatial
      function. Meanwhile, while VCAM-1 level correlated significantly with short-term
      memory (p=0.026) and drawing (p=0.025) scores in the AD patients after adjusting
      for age and education, the significance disappeared after adjusting for global
      FA. Endothelial activation, especially VCAM-1, was of clinical significance in AD
      that reflects macro- and micro-structural changes and poor short term memory and
      visuospatial function. 

PMID- 26289959
TI  - Effect of whole cottonseed v. sunflower seed on the fatty acid profile of
      subcutaneous fat, longissimus dorsi and blood of Thai Native and Holstein bulls.
AB  - In a 2*2 factorial design, 12 Thai Native and 12 Holstein bulls were fed ad
      libitum a total mixed ration (20 : 80; roughage : concentrate) with whole
      cottonseed (WCS) or sunflower seed (SFS) as oilseed sources. The rations
      contained 7% crude fat and were fed for 90 days. Plasma was taken at three times
      during the experiment, and at slaughter the longissimus dorsi and subcutaneous
      fat were sampled for fatty acid analysis. Ration did not affect rumen
      fermentation parameters. The plasma fatty acid profile was not affected by
      ration. In subcutaneous fat, a ration*breed interaction for the saturated fatty
      acid (SFA) and c9t11 CLA proportions was observed, resulting from larger
      differences between the rations in Thai Native compared with Holstein bulls. The
      WCS ration resulted in higher proportions of SFA and lower proportions of
      monounsaturated fatty acids and c9,t11 CLA compared with the SFS ration (P<0.01).
      In the intramuscular fat, the WCS ration was also associated with a lower c9t11
      CLA proportion (P<0.01) and higher SFA proportion (P<0.05). The intramuscular
      proportion of polyunsaturated acids was higher and the proportion of SFA was
      lower in Thai Native compared with Holstein bulls (P<0.05), irrespective of
      ration. 

PMID- 26289960
TI  - Assessing breast cancer cell lines as tumour models by comparison of mRNA
      expression profiles.
AB  - INTRODUCTION: Breast cancer researchers use cell lines to model myriad phenomena
      ranging from DNA repair to cancer stem cell phenotypes. Though appropriate, and
      even requisite, for many studies, the suitability of cell lines as tumour models
      has come into question owing to possibilities of tissue culture artefacts and
      clonal selection. These issues are compounded by the inability of cancer cells
      grown in isolation to fully model the in situ tumour environment, which also
      contains a plethora of non-tumour cell types. It is thus important to understand
      similarities and differences between cancer cell lines and the tumours that they
      represent so that the optimal tumour models can be chosen to answer specific
      research questions. METHODS: In the present study, we compared the RNA-sequencing
      transcriptomes of a collection of breast cancer cell lines to transcriptomes
      obtained from hundreds of tumours using The Cancer Genome Atlas. Tumour purity
      was accounted for by analysis of stromal and immune scores using the ESTIMATE
      algorithm so that differences likely resulting from non-tumour cells could be
      accounted for. RESULTS: We found the transcriptional characteristics of breast
      cancer cell lines to mirror those of the tumours. We identified basal and luminal
      cell lines that are most transcriptionally similar to their respective breast
      tumours. Our comparison of expression profiles revealed pronounced differences
      between breast cancer cell lines and tumours, which could largely be attributed
      to the absence of stromal and immune components in cell culture. A focus on the
      Wnt pathway revealed the transcriptional downregulation or absence of several
      secreted Wnt antagonists in culture. Gene set enrichment analysis suggests that
      cancer cell lines have enhanced proliferation and glycolysis independent of
      stromal and immune contributions compared with breast cancer cells in situ.
      CONCLUSIONS: This study demonstrates that many of the differences between breast
      cancer cell lines and tumours are due to the absence of stromal and immune
      components in vitro. Hence, extra precautions should be taken when modelling
      extracellular proteins in vitro. The specific differences discovered emphasize
      the importance of choosing an appropriate model for each research question.

PMID- 26289961
TI  - Ecosystem productivity is associated with bacterial phylogenetic distance in
      surface marine waters.
AB  - Understanding the link between community diversity and ecosystem function is a
      fundamental aspect of ecology. Systematic losses in biodiversity are widely
      acknowledged but the impact this may exert on ecosystem functioning remains
      ambiguous. There is growing evidence of a positive relationship between species
      richness and ecosystem productivity for terrestrial macro-organisms, but similar
      links for marine micro-organisms, which help drive global climate, are unclear.
      Community manipulation experiments show both positive and negative relationships
      for microbes. These previous studies rely, however, on artificial communities and
      any links between the full diversity of active bacterial communities in the
      environment, their phylogenetic relatedness and ecosystem function remain
      hitherto unexplored. Here, we test the hypothesis that productivity is associated
      with diversity in the metabolically active fraction of microbial communities. We
      show in natural assemblages of active bacteria that communities containing more
      distantly related members were associated with higher bacterial production. The
      positive phylogenetic diversity-productivity relationship was independent of
      community diversity calculated as the Shannon index. From our long-term (7-year)
      survey of surface marine bacterial communities, we also found that similarly,
      productive communities had greater phylogenetic similarity to each other, further
      suggesting that the traits of active bacteria are an important predictor of
      ecosystem productivity. Our findings demonstrate that the evolutionary history of
      the active fraction of a microbial community is critical for understanding their
      role in ecosystem functioning. 

PMID- 26289962
TI  - ATP-sensitive potassium channels: uncovering novel targets for treating
      depression.
AB  - ATP-sensitive potassium (K-ATP) channels have been shown to couple membrane
      electrical activity to energy metabolism in a variety of cells and are important
      in several physiological systems. In the brain, K-ATP channels are strongly
      expressed in the neuronal circuitry. The distributional profile and functional
      significance of K-ATP channels suggest that they may be involved in stress
      induced depression. First, we showed that chronic mild stress (CMS) significantly
      increased the expression of hippocampal Kir6.2 and Kir6.1 subunits of K-ATP
      channels. Next, using Kir6.2 knockout (Kir6.2(-/-)) mice, we presented that
      Kir6.2 deficiency resulted in antidepressant-like behaviors under non-stress
      conditions, but aggravated depressive behaviors accompanied by the loss of CA3
      neuron and the reduction of brain-derived neurotrophic factor in hippocampus
      under chronic stress. Finally, we demonstrated that the K-ATP channel opener
      iptakalim, as well as a classical antidepressant fluoxetine, can reverse CMS
      induced depression-related behaviors and counteract the deleterious effects of
      stress on hippocampus in wild-type mice, but only partially alleviate these
      symptoms in Kir6.2(-/-) mice. Collectively, our findings demonstrate that K-ATP
      channels are involved in the pathogenesis of depression and may be a promising
      target for the therapy of depression.

PMID- 26289963
TI  - Factors determining eligibility and access to subacute rehabilitation for elderly
      people with dementia and hip fracture.
AB  - With hip fracture and dementia increasing in incidence in the global ageing
      population, there is a need for the development of specific procedures targeting
      optimal treatment outcomes for these patients. This paper looks primarily at the
      factors that limit access to subacute rehabilitation services as a growing body
      of evidence suggests that access to timely inpatient rehabilitation increases
      functional outcomes for patients both with dementia and without. Information was
      gathered by searching electronic data bases (SCOPUS, Medline, CINAHL, Health
      Source Nursing/Academic Addition, Psychinfo and the Cochrane Library) for
      relevant articles using the search terms dementia OR Alzheimer* AND hip fracture
      AND subacute rehabilitation OR convalescence for the period 2005-2015. Abstracts
      were scanned to identify articles discussing eligibility and access. A total of
      nine papers were identified that directly addressed this topic. Other papers
      discussing success or failure of rehabilitation and improved models of care were
      also reviewed. Barriers to access discussed in the literature include information
      management, management of comorbidities, attitudes, resource availability, and
      the quality of evidence and education. By identifying these factors we can
      identify strategic points of intervention across the trajectory of prevention,
      treatment and rehabilitation that may improve outcomes for this growing group of
      vulnerable patients. Emerging best practice for these patients is also discussed.

PMID- 26289965
TI  - Highlights of the Tokyo Conference of Asian Pancreato-biliary Interventional
      Endoscopist 2014.

PMID- 26289964
TI  - TGF-betal Suppresses Inflammation in Cell Therapy for Intervertebral Disc
      Degeneration.
AB  - Recent studies suggest that cell therapy may be an effective way to repair
      intervertebral disc degeneration. As a strong immune suppressor, TGF-beta1 has
      been shown to inhibit inflammation respond effectively. The objective of this
      study was to explore the effects of TGF-beta1 during bone marrow mesenchymal stem
      cells-based therapy for disc degeneration. In vitro assays demonstrated that co
      culturing of nucleus pulposus cells with bone marrow mesenchymal stem cells
      resulted in significantly higher levels of TGF-betal secretion. This increase
      inhibited IkappaB phosphorylation and NF-kappaB activation, detected by western
      blot analysis. Meanwhile, in a rabbit model, MRI analysis revealed significant
      recovery of signal intensity in the degenerative discs of rabbits receiving cells
      transplantation, than receiving cells treated with a TGF-beta1 inhibitor or
      saline. These findings indicated that enhanced TGF-beta1 production recovered the
      degeneration of intervertebral disc. And also immunohistochemical staining
      detected enhanced collagen II expression in the rabbits treated with cell
      transplantation. However, the NF-kappaB positive cells were significantly less
      than other two control groups. Thus, cell therapy promoted TGF-beta1 expression
      in nucleus pulposus, leading to anti-inflammatory effects via the inhibition of
      NF-kappaB, and the amelioration of disc degradation due to increased expression
      of collagen II and aggrecan in degenerative intervertebral disc. 

PMID- 26289966
TI  - Sexual dimorphism in a trophically polymorphic cichlid fish?
AB  - Sexual dimorphism in ecologically relevant traits is ubiquitous in animals.
      However, other types of intraspecific phenotypic divergence, such as trophic
      polymorphism, are less common. Because linkage to sex should often lead to
      balancing selection, understanding the association between sex and phenotypic
      divergence could help explain why particular species show high morphological
      variability. To determine if sexual dimorphism could be helping to maintain
      ecomorphological variation in a classic case of intraspecific trophic
      polymorphism, we examined the association between sex and morphological
      divergence in the cichlid Herichthys minckleyi. Although H. minckleyi with
      enlarged molariform teeth on their pharyngeal jaws have been reported to more
      commonly be male, we did not find an association between sex and pharyngeal
      morphotype. Sex was associated with divergence in body size (as measured through
      standard length). But, sex was not associated with any of the other trophic
      traits examined. However, pharyngeal morphotype did show an association with gut
      length, gape, and tooth number. Sexual dimorphism is not playing a central role
      in enhancing trophic diversity within H. minckleyi.

PMID- 26289967
TI  - Combined Algorithm Using a Poor Increase in Inferior P-Wave Amplitude During
      Sympathetic Stimulation and Sinus Node Recovery Time for the Diagnosis of Sick
      Sinus Syndrome.
AB  - BACKGROUND: This study sought to evaluate whether a poor increase in inferior P
      wave amplitude during sympathetic stimulation might be a helpful diagnostic tool
      for sick sinus syndrome (SSS). METHODS AND RESULTS: Three-dimensional
      electroanatomic mapping of the right atrium, inferior P-wave amplitude and
      conventional corrected sinus node recovery time (CSNRT) were compared in 112
      consecutive atrial fibrillation (AF) patients with (n=21) and without SSS (n=91).
      The significant cranial shift of earliest activation site (EAS) (the distance
      from the superior vena cava to the EAS: 11.1 vs. 5.9 mm, P<0.001) and the
      increases of inferior P-wave amplitudes during isoproterenol infusion (all
      P<0.001) were observed in patients without SSS. However, cranial shift of EAS
      (16.5 vs. 14.2 mm, P=0.375) and P-wave amplitude increases were not observed in
      those with SSS. Although CSNRT >550 ms showed a sensitivity of 50% and
      specificity of 84% for diagnosing SSS, poor increases of P-waves amplitude in
      lead aVF (<0.1 mV) during isoproterenol infusion showed an improved sensitivity
      of 71% and specificity of 89%. Finally, the combined algorithm using CSNRT >550
      ms and poor increase of P-waves amplitude in lead aVF showed more improved
      diagnostic accuracy (sensitivity 89%, specificity 75%). CONCLUSIONS: A combined
      algorithm using inferior P-wave amplitude showed improved performance for the
      diagnosis of SSS compared with CSNRT >550 ms alone.

PMID- 26289968
TI  - "The Third Man" in Heart Failure--Heart Failure With Reduce Ejection Fraction
      Evolved From Heart Failure With Preserved Ejection Fraction.

PMID- 26289969
TI  - Coronary artery problems late after arterial switch operation for transposition
      of the great arteries.
AB  - BACKGROUND: The incidence of late coronary artery abnormalities after arterial
      switch operation (ASO) for d-loop transposition of the great arteries may be
      underestimated. METHODS AND RESULTS: We retrospectively reviewed coronary artery
      morphology in 40 of 97 patients who survived the first year after ASO. Seven
      asymptomatic patients developed significant late coronary artery abnormalities.
      One patient died suddenly at home with severe left coronary artery (LCA) ostial
      stenosis at age 3.8 years. The second patient collapsed during exercise at age
      9.6 years due to ventricular fibrillation and severe LCA ostial stenosis despite
      prior negative exercise stress test (EST) and myocardial perfusion imaging (MPI).
      The third patient was found to have moderate ostial stenosis of the LCA with
      negative EST and MPI. The fourth patient with exercise-induced ST-T depression
      and myocardial perfusion defect was shown to have complete LCA occlusion with
      collateral vessel formation. Three other patients had complete proximal
      obliteration of either of the coronary arteries with collateral supply. An
      additional 4 asymptomatic patients had trivial-mild narrowing of the LCA on
      routine selective coronary angiogram. CONCLUSIONS: Incidence of late coronary
      stenosis or occlusion was not infrequent after ASO (11.3%) and presented usually
      without preceding symptoms and often after negative non-invasive screening. We
      advocate routine coronary imaging in all patients after ASO before they
      participate in competitive sports.

PMID- 26289970
TI  - Improving credibility and transparency of conservation impact evaluations through
      the partial identification approach.
AB  - The fundamental challenge of evaluating the impact of conservation interventions
      is that researchers must estimate the difference between the outcome after an
      intervention occurred and what the outcome would have been without it
      (counterfactual). Because the counterfactual is unobservable, researchers must
      make an untestable assumption that some units (e.g., organisms or sites) that
      were not exposed to the intervention can be used as a surrogate for the
      counterfactual (control). The conventional approach is to make a point estimate
      (i.e., single number along with a confidence interval) of impact, using, for
      example, regression. Point estimates provide powerful conclusions, but in
      nonexperimental contexts they depend on strong assumptions about the
      counterfactual that often lack transparency and credibility. An alternative
      approach, called partial identification (PI), is to first estimate what the
      counterfactual bounds would be if the weakest possible assumptions were made.
      Then, one narrows the bounds by using stronger but credible assumptions based on
      an understanding of why units were selected for the intervention and how they
      might respond to it. We applied this approach and compared it with conventional
      approaches by estimating the impact of a conservation program that removed
      invasive trees in part of the Cape Floristic Region. Even when we used our
      largest PI impact estimate, the program's control costs were 1.4 times higher
      than previously estimated. PI holds promise for applications in conservation
      science because it encourages researchers to better understand and account for
      treatment selection biases; can offer insights into the plausibility of
      conventional point-estimate approaches; could reduce the problem of advocacy in
      science; might be easier for stakeholders to agree on a bounded estimate than a
      point estimate where impacts are contentious; and requires only basic arithmetic
      skills. 

PMID- 26289971
TI  - The Neck Disability Index (NDI) and its correlation with quality of life and
      mental health measures among patients with single-level cervical disc disease
      scheduled for surgery.
AB  - BACKGROUND: The Neck Disability Index (NDI) is widely used as a self-rated
      disability score in patients with cervical radiculopathy. The purpose of this
      study was to evaluate whether the NDI score correlated with other assessments of
      quality of life and mental health in a specific group of patients with single
      level cervical disc disease and corresponding radiculopathy. METHODS: One hundred
      thirty-six patients were included in a prospective, randomized controlled
      clinical multicenter study on one-level anterior cervical discectomy with
      arthroplasty (ACDA) versus one-level anterior cervical discectomy with fusion
      (ACDF). The preoperative data were obtained at hospital admission 1 to 3 days
      prior to surgery. The NDI score was used as the dependent variable and
      correlation as well as regression analyses were conducted to assess the
      relationship with the short form-36, EuroQol-5Dimension-3 level and Hospital
      Anxiety and Depression Scale. RESULTS: The mean age at inclusion was 44.1 years
      (SD +/-7.0, range 26-59 years), of which 46.3 % were male. Mean NDI score was
      48.6 (SD = 12.3, minimum 30 and maximum 88). Simple linear regression analysis
      demonstrated a significant correlation between NDI and the EuroQol-5Dimension-3
      level [R = -0.64, 95 % confidence interval (CI) -30.1- -19.8, p < 0.001] and to a
      lesser extent between NDI and the short form-36 physical component summary [R = 
      0.49, 95 % CI (-1.10- -0.58), p < 0.001] and the short form-36 mental component
      summary [R = -0.25, 95 % CI (-0.47- -0-09), p = 0.004]. Regarding NDI and the
      Hospital Anxiety and Depression Scale, a significant correlation for depression
      was found [R = 0.26, 95 % CI (0.21-1.73), p = 0.01]. Multiple linear regression
      analysis showed a statistically significant and the strongest correlation between
      NDI and the independent variables in the following order: EuroQol-5Dimension-3
      level [R = -0.64, 95 % CI (-23.5- -7.9), p <0.001], short form-36 physical
      component summary [R = -0.41, 95 % CI (-0.93- -0.23), p = 0.001] and short form
      36 mental component summary [R = -0.36, 95 % CI (-0.53- -0.15), p = 0.001].
      CONCLUSION: The results from the present study show that the NDI correlated
      significantly with a different quality of life and mental health measures among
      patients with single-level cervical disc disease and corresponding radiculopathy.

PMID- 26289972
TI  - Vaccine-preventable infection morbidity of patients with chronic kidney disease
      and cocoon vaccination strategies.
AB  - Individuals with chronic kidney disease (CKD) are vulnerable to vaccine
      preventable infections due to impaired immunity, immunosuppressive treatments and
      dialysis. Protection of CKD patients by vaccination is hampered by reduced
      efficacy of vaccines and safety concerns for transplant candidates or recipients.
      'Cocooning' vaccination policies, targeting the protection of a vulnerable
      individual through immunization of close contacts, have recently been introduced
      for infants and, to a lesser degree, for high-risk groups of immunocompromised
      individuals. In this article, we discuss the potentiality of implementing cocoon
      strategies for the high-risk group of CKD patients and conclude that this not yet
      officially recommended policy can substantially contribute to protection against
      infection and motivate vaccination among families and healthcare workers. 

PMID- 26289973
TI  - The impact of 10-valent and 13-valent pneumococcal conjugate vaccines on serotype
      19A invasive pneumococcal disease.
AB  - The circulation in the community of pneumococcal serotype 19A, a highly invasive
      and frequently extremely resistant pneumococcal strain, has increased the focus
      on methods to control its presence and effect. Two vaccines have been developed:
      the 10-valent pneumococcal conjugate vaccine (PCV10) and the 13-valent
      pneumococcal conjugate vaccine (PCV13). Available data indicate that PCV13 is
      highly effective in reducing the risk of serotype 19A invasive pneumococcal
      disease (IPD) in both vaccinated children and unvaccinated adults. Positive data
      have also been published for PCV10 that suggest that the conjugated serotype 19F
      included in the vaccine could evoke a cross-reactive antibody response with
      serotype 19A. However, a great number of invasive pneumococcal disease (IPD)
      cases are associated with serotypes not included in either of the vaccines, and
      preparation of a vaccine containing all the serotypes is unrealistic. Protein
      vaccines are the real future to definitively reduce the pneumococcal disease
      burden. 

PMID- 26289974
TI  - Neonatal group B streptococcus disease in developing countries: are we ready to
      deploy a vaccine?
AB  - Group B streptococcus (GBS) disease is the leading cause of neonatal sepsis in
      developed countries and has high case fatality rates. In developing countries,
      however, the burden of GBS is less clear; this is due to a lack of studies using
      optimal diagnostic, clinical and laboratory techniques and is complicated by the
      wide availability of non-prescription antibiotics to the general population and
      in peripartum patients. There is an urgent need for prospective, population-based
      surveillance to provide an accurate assessment of neonatal GBS disease burden in
      developing countries, which remains largely unrecognized, and consequently
      obscures the potential relevance of GBS vaccination in these populations.
      Preliminary data on GBS vaccines are promising as a preventive tool for neonatal
      GBS infection, more so than any other currently available public health
      initiative. However, how do we assess the true impact of a GBS vaccine without
      accurate surveillance data on the real burden of disease? 

PMID- 26289975
TI  - Safety, immunogenicity and infectivity of new live attenuated influenza vaccines.
AB  - Live attenuated influenza vaccines (LAIVs) are believed to be immunologically
      superior to inactivated influenza vaccines, because they can induce a variety of
      adaptive immune responses, including serum antibodies, mucosal and cell-mediated
      immunity. In addition to the licensed cold-adapted LAIV backbones, a number of
      alternative LAIV approaches are currently being developed and evaluated in
      preclinical and clinical studies. This review summarizes recent progress in the
      development and evaluation of LAIVs, with special attention to their safety,
      immunogenicity and infectivity for humans, and discusses their perspectives for
      the future. 

PMID- 26289976
TI  - Tick vaccines: current status and future directions.
AB  - Ticks and tick-borne diseases are a growing problem affecting human and animal
      health worldwide. Traditional control methods, based primarily on chemical
      acaricides, have proven not to be sustainable because of the selection of
      acaricide-resistant ticks. Tick vaccines appear to be a promising and effective
      alternative for control of tick infestations and pathogen transmission. The
      purpose of this review is to summarize previous tick vaccine development and
      performance and formulate critical issues and recommendations for future
      directions for the development of improved and effective tick vaccines. The
      development of effective screening platforms and algorithms using omics
      approaches focused on relevant biological processes will allow the discovery of
      new tick-protective antigens. Future vaccines will likely combine tick antigens
      with different protective mechanisms alone or pathogen-derived antigens. The
      application of tick vaccines as a part of integrated control strategies will
      ultimately result in the control of tick-borne diseases. 

PMID- 26289977
TI  - Adenovirus-vectored Ebola vaccines.
AB  - The 2014 outbreak of Ebola virus disease in West Africa has highlighted the need
      for the availability of effective vaccines against outbreak pathogens that are
      suitable for use in frontline workers who risk their own health in the course of
      caring for those with the disease, and also for members of the community in the
      affected area. Along with effective contact tracing and quarantine, use of a
      vaccine as soon as an outbreak is identified could greatly facilitate rapid
      control and prevent the outbreak from spreading. This review describes the
      progress that has been made in producing and testing adenovirus-based Ebola
      vaccines in both pre-clinical and clinical studies, and considers the likely
      future use of these vaccines. 

PMID- 26289978
TI  - [Comparative Study of Patient Identifications for Conventional and Portable Chest
      Radiographs Utilizing ROC Analysis].
AB  - To evaluate the patient identification ability of radiographers, previous and
      current chest radiographs were assessed with observer study utilizing a receiver
      operating characteristics (ROCs) analysis. This study included portable and
      conventional chest radiographs from 43 same and 43 different patients. The
      dataset used in this study was divided into the three following groups: (1) a
      pair of portable radiographs, (2) a pair of conventional radiographs, and (3) a
      combination of each type of radiograph. Seven observers participated in this ROC
      study, which aimed to identify same or different patients, using these datasets.
      ROC analysis was conducted to calculate the average area under ROC curve obtained
      by each observer (AUCave), and a statistical test was performed using the multi
      reader multi-case method. Comparable results were obtained with pairs of portable
      (AUCave: 0.949) and conventional radiographs (AUCave: 0.951). In a comparison
      between the same modality, there were no significant differences. In contrast,
      the ability to identify patients by comparing a portable and conventional
      radiograph (AUCave: 0.873) was lower than with the matching datasets (p=0.002 and
      p=0.004, respectively). In conclusion, the use of different imaging modalities
      reduces radiographers' ability to identify their patients. 

PMID- 26289979
TI  - [Assessment of Inspection Technology of Dopamine Transporter Imaging with 123I
      Ioflupane].
AB  - Imaging start time of single-photon emission computed tomography (SPECT) scan is
      recommended between 3 hours and 6 hours after injection of 123I-ioflupane in
      Ioflupane clinical practice guidelines. But image includes the effect of
      physiological actions of the human body and the attenuation at 13.27 hours
      physical half-life of 123I. Therefore, we evaluated the effect of the image by
      the elapsed time of imaging start time. Optimal cut-off frequency of Butterworth
      filter were examined phantom by normalized mean square error. Count was reduced
      by 23.1% in 5 hours, but cut-off frequency of Butterworth filter was 0.11
      cycle/pixel in 0-5 hours from phantom data. Ten subjects (age 55-85 years) were
      injected with 123I-ioflupane of 110-199 MBq into the vein only once. And we
      examined the specific binding ratio (SBR) in inspection of injection after 5. 5
      hours and 3 hours. Decrease of counts value increased the coefficient of variance
      (CV) between 3 hours and 5.5 hours after injection, but the improvement of
      statistical noise by pre-processing filter reduced the CV. No significant
      difference in the result of SBR was found between 3 hours and 5. 5 hours after
      injection. Our results suggest that imaging start time of SPECT scan is
      recommended between 3 hours and 5.5 hours after injection of 123I-ioflupane.

PMID- 26289980
TI  - [Validity of the Signal-to-noise Ratio Measurement Method for MRI Using a Phase
      Image].
AB  - The most common methods to determine the signal-to-noise ratio (SNR) of magnetic
      resonance imaging (MRI) are based on the signal statistics in regions of interest
      (ROIs) in a magnitude image. For this, methods to calculate the ROI have still
      several discussions; we assumed SNR of a magnitude image could be estimated from
      standard deviation of a phase image (the phase method). The purpose of this study
      is to evaluate the validity of the phase method to determine the SNR. The
      simulation using digital phantom was carried out for evaluation of the effect to
      measure SNR; fluctuation in the phase image and SNR of the magnitude image. The
      phantom study was also performed for evaluation of the validity of estimation
      using the phase method in comparison with the conventional method (the identical
      ROI method and the subtraction method). The result of the simulation showed that
      SNR of magnitude image is larger than 4 for the SNR measurement using the phase
      method and this results reliable. The influence of fluctuation of the phase image
      should be eliminated for practical purposes. In the phantom study, phase method
      showed similar results compared to conventional methods in condition with
      elimination of the fluctuation of the phase image. Though there was a difference
      in the results of the phase method and the subtraction method according to the
      position of the ROI, the error was less than 4%. In this study, the method using
      the phase image to determine the SNR was identified as valuable. 

PMID- 26289981
TI  - [Assessment of Left Ventricular Systolic and Diastolic Function with
      Retrospective Electrocardiogram Triggered 320-row Area Detector Computed
      Tomography: A Comparison with Ultrasound Echocardiography].
AB  - BACKGROUND: The 320-row area detector computed tomography (ADCT) for the
      evaluation of left ventricular (LV) systolic function has been reported, but
      reporting of ADCT for the evaluation of LV diastolic function (LVDF) cannot be
      found. The purpose of this study was to examine the usefulness of ADCT in the
      assessment of LV systolic and diastolic function compared to ultrasound
      echocardiography (Echo) as the standard of reference. MATERIALS AND METHODS: We
      evaluated 60 consecutive patients (mean age 62.4 +/- 13.2 years, male/female
      36/24) who underwent ADCT (retrospective electrocardiogram triggered) and Echo.
      All patients were classified into three groups (A, B, C) according to LVDF
      evaluated by Echo. We examined peak filling rate (PFR) and time to peak filling
      (TPF) as indicator of LVDF using ADCT. RESULTS: Good correlations between ADCT
      and Echo were demonstrated for the assessment of LVSF. PFR of group B (mild
      diastolic dysfunction) patients (1.92 +/- 0.69) and group C (moderate severe
      diastolic dysfunction) patients (1.90 +/- 0.75) were significantly lower than
      that of group A (normal diastolic function) patients (2.50 +/- 0.43). TPF of
      group B (191.6 +/- 54.4 ms) and group C patients (197.5 +/- 64.0 ms) were
      significantly higher than that of group A patients (149.5+/-34.1 ms).
      CONCLUSIONS: ADCT is useful method for the evaluation of LVSF and LV diastolic
      dysfunction.

PMID- 26289982
TI  - [Evaluation of an Experimental Production Wireless Dose Monitoring System for
      Radiation Exposure Management of Medical Staff].
AB  - Because of the more advanced and more complex procedures in interventional
      radiology, longer treatment times have become necessary. Therefore, it is
      important to determine the exposure doses received by operators and patients. The
      aim of our study was to evaluate an experimental production wireless dose
      monitoring system for pulse radiation in diagnostic X-ray. The energy, dose rate,
      and pulse fluoroscopy dependence were evaluated as the basic characteristics of
      this system for diagnostic X-ray using a fully digital fluoroscopy system. The
      error of 1 cm dose equivalent rate was less than 15% from 35.1 keV to 43.2 keV
      with energy correction using metal filter. It was possible to accurately measure
      the dose rate dependence of this system, which was highly linear until 100
      MUSv/h. This system showed a constant response to the pulse fluoroscopy. This
      system will become useful wireless dosimeter for the individual exposure
      management by improving the high dose rate and the energy characteristics. 

PMID- 26289983
TI  - [12. Future Perspective of Monte Carlo Method].

PMID- 26289984
TI  - [9. Radiation Therapy for Brain Tumor-No. 2 Focus on Ion Beam Radiotherapy].

PMID- 26289986
TI  - [Introduction of Small and Medium Enterprise and Information Technology Industry
      Promotion Committee (SME?IT Committee)].

PMID- 26289987
TI  - [New Challenge of JSRT].

PMID- 26289988
TI  - Which non-technical skills do junior doctors require to prescribe safely? A
      systematic review.
AB  - AIMS: Prescribing errors are a major source of avoidable morbidity and mortality.
      Junior doctors write most in-hospital prescriptions and are the least experienced
      members of the healthcare team. This puts them at high risk of error and makes
      them attractive targets for interventions to improve prescription safety. Error
      analysis has shown a background of complex environments with multiple
      contributory conditions. Similar conditions in other high risk industries, such
      as aviation, have led to an increased understanding of so-called human factors
      and the use of non-technical skills (NTS) training to try to reduce error. To
      date no research has examined the NTS required for safe prescribing. The aim of
      this review was to develop a prototype NTS taxonomy for safe prescribing, by
      junior doctors, in hospital settings. METHODS: A systematic search identified 14
      studies analyzing prescribing behaviours and errors by junior doctors. Framework
      analysis was used to extract data from the studies and identify behaviours
      related to categories of NTS that might be relevant to safe and effective
      prescribing performance by junior doctors. Categories were derived from existing
      literature and inductively from the data. RESULTS: A prototype taxonomy of
      relevant categories (situational awareness, decision making, communication and
      team working, and task management) and elements was constructed. CONCLUSIONS:
      This prototype will form the basis of future work to create a tool that can be
      used for training and assessment of medical students and junior doctors to reduce
      prescribing error in the future.

PMID- 26289989
TI  - Clinical and genetic characteristics of craniosynostosis in Hungary.
AB  - Craniosynostosis, the premature closure of cranial sutures, is a common
      craniofacial disorder with heterogeneous etiology and appearance. The purpose of
      this study was to investigate the clinical and molecular characteristics of
      craniosynostoses in Hungary, including the classification of patients and the
      genetic analysis of the syndromic forms. Between 2006 and 2012, 200 patients with
      craniosynostosis were studied. Classification was based on the suture(s) involved
      and the associated clinical features. In syndromic cases, genetic analyses,
      including mutational screening of the hotspot regions of the FGFR1, FGFR2, FGFR3,
      and TWIST1 genes, karyotyping and FISH study of TWIST1, were performed. The
      majority (88%) of all patients with craniosynostosis were nonsyndromic. The
      sagittal suture was most commonly involved, followed by the coronal, metopic, and
      lambdoid sutures. Male, twin gestation, and very low birth weight were risk
      factors for craniosynostosis. Syndromic craniosynostosis was detected in 24
      patients. In 17 of these patients, Apert, Crouzon, Pfeiffer, Muenke, or Saethre
      Chotzen syndromes were identified. In one patient, multiple-suture
      craniosynostosis was associated with achondroplasia. Clinical signs were not
      typical for any particular syndrome in six patients. Genetic abnormalities were
      detected in 18 syndromic patients and in 8 relatives. In addition to 10
      different, known mutations in FGFR1,FGFR2 or FGFR3, one novel missense mutation,
      c.528C>G(p.Ser176Arg), was detected in the TWIST1 gene of a patient with Saethre
      Chotzen syndrome. Our results indicate that detailed clinical assessment is of
      paramount importance in the classification of patients and allows indication of
      targeted molecular testing with the highest possible diagnostic yield.

PMID- 26289990
TI  - The influence of early maternal care on perceptual attentional set shifting and
      stress reactivity in adult rats.
AB  - Stress influences a wide variety of outcomes including cognitive processing. In
      the rat, early life maternal care can influence developing offspring to affect
      both stress reactivity and cognitive processes in adulthood. The current study
      assessed if variations in early life maternal care can influence cognitive
      performance on a task, the ability to switch cognitive sets, dependent on the
      medial prefrontal cortex. Early in life, offspring was reared under High or Low
      maternal Licking conditions. As adults, they were trained daily and then tested
      on an attentional set-shifting task (ASST), which targets cognitive flexibility
      in rodents. Stress-sensitive behavioral and neural markers were assayed before
      and after the ASST. High and Low Licking offspring performed equally well on the
      ASST despite initial, but not later, differences in stress axis functioning.
      These results suggest that early life maternal care does not impact the accuracy
      of attentional set-shifting in rats. These findings may be of particular
      importance for those interested in the relationship between early life experience
      and adult cognitive function.

PMID- 26289991
TI  - Neurocognitive Effects of Obesity and Bariatric Surgery.
AB  - This review paper will discuss the recent literature examining the relationship
      between obesity and neurocognitive outcomes, with a particular focus on cognitive
      changes after bariatric surgery. Obesity is now recognized as an independent risk
      factor for adverse neurocognitive outcomes, and severely obese persons appear to
      be at even greater risk. Bariatric surgery is associated with rapid improvements
      in cognitive function that persist for at least several years, although the
      mechanisms underlying these improvements are incompletely understood. Assessment
      of cognitive impairment in bariatric surgery patients is challenging, and
      improved methods are needed, as poorer performance on neuropsychological tests of
      memory and executive function leads to poorer clinical weight outcomes. In
      addition to its clinical importance, further study in this area will provide key
      insight into obesity-related cognitive dysfunction and clarify the possibility of
      an obesity paradox for neurological outcomes.

PMID- 26289992
TI  - Priming and memory of stress responses in organisms lacking a nervous system.
AB  - Experience and memory of environmental stimuli that indicate future stress can
      prepare (prime) organismic stress responses even in species lacking a nervous
      system. The process through which such organisms prepare their phenotype for an
      improved response to future stress has been termed 'priming'. However, other
      terms are also used for this phenomenon, especially when considering priming in
      different types of organisms and when referring to different stressors. Here we
      propose a conceptual framework for priming of stress responses in bacteria, fungi
      and plants which allows comparison of priming with other terms, e.g. adaptation,
      acclimation, induction, acquired resistance and cross protection. We address
      spatial and temporal aspects of priming and highlight current knowledge about the
      mechanisms necessary for information storage which range from epigenetic marks to
      the accumulation of (dormant) signalling molecules. Furthermore, we outline
      possible patterns of primed stress responses. Finally, we link the ability of
      organisms to become primed for stress responses (their 'primability') with
      evolutionary ecology aspects and discuss which properties of an organism and its
      environment may favour the evolution of priming of stress responses.

PMID- 26289993
TI  - Detection and characterization of respiratory viruses causing acute respiratory
      illness and asthma exacerbation in children during three different seasons (2011
      2014) in Mexico City.
AB  - BACKGROUND: Viral infections play a significant role in causing acute respiratory
      infections (ARIs) and exacerbations of chronic diseases. Acute respiratory
      infections are now the leading cause of mortality in children worldwide,
      especially in developing countries. Recently, human rhinovirus (HRV) infection
      has been emerged as an important cause of pneumonia and asthma exacerbation.
      OBJECTIVES: To determine the role of several viral agents principally,
      respiratory syncytial virus, and HRV in children with ARIs and their relationship
      with asthma exacerbation and pneumonia. METHODS: Between October 2011 and March
      2014, 432 nasopharyngeal samples of children <15 years of age with ARI
      hospitalized at a referral hospital for respiratory diseases were tested for the
      presence of respiratory viruses using a multiplex RT-qPCR. Clinical,
      epidemiological, and demographic data were collected and associated with
      symptomatology and viral infections. RESULTS: Viral infections were detected in
      at least 59.7% of the enrolled patients, with HRV (26.6%) being the most
      frequently detected. HRV infections were associated with clinical features of
      asthma and difficulty in breathing such as wheezing (P = 0.0003), supraesternal
      (P = 0.046), and xiphoid retraction (P = 0.030). HRV subtype C (HRV-C) infections
      were associated with asthma (P = 0.02). CONCLUSIONS: Human rhinovirus was the
      virus most commonly detected in pediatric patients with ARI. There is also an
      association of HRV-C infection with asthma exacerbation, emphasizing the
      relevance of this virus in severe pediatric respiratory disease.

PMID- 26289994
TI  - What can happen to food.

PMID- 26289995
TI  - Religiosity and Health-Related Quality of Life: A Cross-Sectional Study on
      Filipino Christian Hemodialysis Patients.
AB  - This study aimed to measure the religiosity and health-related quality of life of
      Filipino Christian HD patients. A cross-sectional study of 100 HD patients was
      conducted. The Duke University Religion Index and the Ferrans and Powers QLI
      Dialysis Version-III were used. Data were analyzed using descriptive statistics
      and Pearson r correlation. Attendance to organizational religious activities and
      NORA were found to be correlated with some of the dimensions of HRQoL. Intrinsic
      religiosity showed a strong, positive correlation with HRQoL. It is essential to
      attend to and nourish their religious needs. Holistic approach in providing care
      to HD patients, with emphasis on spiritual care, is encouraged to improve their
      total health. 

PMID- 26289996
TI  - Resistance exercise and naproxen sodium: effects on a stable PGF2alpha metabolite
      and morphological adaptations of the upper body appendicular skeleton.
AB  - INTRODUCTION: Exercise-induced inflammation has been shown to be necessary for
      successful skeletal muscle regeneration post-injury. Accordingly, numerous
      investigations have demonstrated consequences of COX-inhibitors, anti
      inflammatory drugs which prevent prostaglandin formation. In addition to its
      roles in inflammation, prostaglandin F2alpha (PGF2alpha) also mediates vital
      regenerative processes The majority of research to report consequences of
      suppressing inflammation has utilized acute injury models in combination with
      acute COX-inhibitor administration. To address the limited research investigating
      regular consumption of COX-inhibitors over time in exercising humans, the purpose
      of this study was to determine effects of a non-selective COX-inhibitor on a
      PGF2alpha metabolite and morphological adaptations of the upper body appendicular
      skeleton during periodized resistance training. Twenty-three (N = 23)
      recreationally trained college-aged males were randomly assigned to receive
      placebo (n = 11) or naproxen sodium (n = 12). Treatments were prophylactically
      administered in double-blind fashion with supervised upper body resistance
      exercise performed twice per week for 6 weeks. Venous blood was sampled pre- and
      post-exercise and analyzed for 13, 14-dihydro-15-keto PGF2alpha using enzyme
      immunoassay. Factorial mixed-design repeated-measures ANOVAs were utilized to
      examine relative changes in the plasma PGF2alpha metabolite and upper body
      appendicular morphology over the training period. RESULTS: Naproxen sodium
      significantly reduced the acute PGF2alpha metabolite response to exercise (p =
      0.013); however, this effect diminished over time (p = 0.02), and both treatment
      groups exhibited significant increases in dominant arm skeletal muscle tissue (p
      = 0.037). CONCLUSION: Despite acute inhibition of the PGF2alpha metabolite at
      early time points, naproxen sodium did not hinder positive morphological
      adaptations of the upper body in response to resistance training.

PMID- 26289998
TI  - 25th Biennial Meeting of the International Society for Neurochemistry jointly
      with the 13th Meeting of the Asian-Pacific Society for Neurochemistry in
      conjunction with the 35th Meeting of the Australasian Neuroscience Society 23-27
      August 2015, Cairns, Australia.

PMID- 26289997
TI  - The Future of Dry Eye Treatment: A Glance into the Therapeutic Pipeline.
AB  - Dry eye syndrome is both a primary disease and a secondary result of many
      pathological states of the eye. The symptoms range from mild to severe itching,
      burning, irritation, eye fatigue, and even vision loss that can lead to
      disability. Dry eye affects approximately 60 million people worldwide; as a
      result, medications to treat dry eye comprise approximately 15% of the ophthalmic
      pharmaceutical market. While doctors and patients eagerly await new treatments,
      pharmaceuticals in the pipeline are moving through the approval process with
      several promising drugs having completed phase 3 clinical testing. This review
      summarizes the findings of studies of the most promising, upcoming dry eye
      treatments in phase 2 and 3 clinical trials in the USA. 

PMID- 26289999
TI  - Stabilizing prevalence trends of eczema, asthma and rhinoconjunctivitis in Dutch
      schoolchildren (2001-2010).
AB  - In contrast to many countries, a decrease in childhood wheeze prevalence was
      previously reported for the Netherlands. In repeated cross-sectional surveys in
      2001, 2005 and 2010, we investigated whether this trend continued, and
      additionally examined prevalence trends of eczema, asthma and rhinoconjunctivitis
      among 8- to 11-year-old schoolchildren eligible for a routine physical
      examination. Overall, ~90% participated (mean age: 8.8 years in 2001 and 10.5
      years in 2005 and 2010). Eczema, wheeze and asthma prevalence did not change
      significantly between 2001 and 2010, but rhinoconjunctivitis prevalence increased
      from 8.4% in 2001 to 12.3% in both 2005 and 2010 (Ptrend < 0.01). In conclusion,
      after a decrease in wheeze prevalence among Dutch schoolchildren between 1989 and
      2001, no further decrease was observed until 2010. Similarly, the prevalence of
      eczema and asthma remained stable, but rhinoconjunctivitis prevalence increased
      between 2001 and 2010. The latter may be an effect of older age and not a true
      increase over time. 

PMID- 26290000
TI  - Will preoperative scoring of patients referred for cataract surgery change
      indications for surgery? Preliminary results using the Swedish NIKE system in
      Copenhagen.

PMID- 26290002
TI  - Reliability of Identification of Behavior Change Techniques in Intervention
      Descriptions.
AB  - PURPOSE: The aim of this paper is to assess the frequency of identification as
      well as the inter-coder and test-retest reliability of identification of behavior
      change techniques (BCTs) in written intervention descriptions. METHODS: Forty
      trained coders applied the "Behavior Change Technique Taxonomy version 1"
      (BCTTv1) to 40 intervention descriptions published in protocols and repeated this
      1 month later. RESULTS: Eighty of 93 defined BCTs were identified by at least one
      trained coder, and 22 BCTs were identified in 16 (40 %) or more of 40
      descriptions. Good inter-coder reliability was observed across 80 BCTs identified
      in the protocols: 66 (80 %) achieved mean prevalence and bias-adjusted kappa
      (PABAK) scores of 0.70 or greater, and 59 (74 %) achieved mean scores of 0.80 or
      greater. There was good within-coder agreement between baseline and 1 month,
      demonstrating good test-retest reliability. CONCLUSIONS: BCTTv1 can be used by
      trained coders to identify BCTs in intervention descriptions reliably. However,
      some frequently occurring BCT definitions require further clarification.

PMID- 26290001
TI  - Cognitive Behavioral Stress Management for Healthy Women at Risk for Breast
      Cancer: a Novel Application of a Proven Intervention.
AB  - BACKGROUND: Women at risk for breast cancer report elevated psychological
      distress, which has been adversely associated with cancer-relevant behaviors and
      biology. PURPOSE: The present study sought to examine the effects of a 10-week
      cognitive behavioral stress management (CBSM) group intervention on distress
      among women with a family history of breast cancer. METHODS: Participants were
      randomly assigned to CBSM (N = 82) or a wait-list comparison group (N = 76).
      Baseline to postintervention effects of CBSM on depressive symptoms and perceived
      stress were examined using hierarchical regression. RESULTS: CBSM participants
      reported significantly lower posttreatment depressive symptoms (beta = -0.17, p <
      0.05) and perceived stress (beta = -0.23, p < 0.05) than wait-list comparison
      participants. Additionally, greater relaxation practice predicted lower distress.
      CONCLUSIONS: Group-based CBSM intervention is feasible and can reduce
      psychological distress among women with a family history of breast cancer. The
      present findings represent an encouraging avenue for the future application of
      CBSM. ( Clinicaltrials.gov number NCT00121160).

PMID- 26290003
TI  - Equine Dermatophytosis due to Trichophyton bullosum, a Poorly Known Zoophilic
      Dermatophyte Masquerading as T. verrucosum.
AB  - Trichophyton bullosum is a zoophilic dermatophyte from the Arthroderma benhamiae
      complex with a poorly known distribution. In this study, we report a case of
      dermatophytosis caused by T. bullosum in a 6-year-old male horse who had a skin
      lesion located in a saddle area. The infection spread rapidly to the upper chest
      and to both sides of the trunk. The dermatophyte was isolated in culture and
      identified by sequence analysis of the internal transcribed spacer regions (ITS
      rDNA). To date, this is the first verified case of animal infection due to T.
      bullosum in Europe following the 2012 report of human infection in France. We
      hypothesize that this species can be relatively common in horses and donkeys, but
      it is confused with other zoophilic species responsible for infections with
      similar clinical manifestations, and when isolated in culture, it is
      misidentified as the phenotypically similar T. verrucosum. Previous cases of
      dermatophytosis caused by T. verrucosum-like dermatophytes in horses and donkeys
      were reviewed together with human infections transmitted from these animals. This
      summary estimates possible distribution width of T. bullosum. The taxonomy of T.
      verrucosum-like dermatophytes is extremely difficult due to lack of original
      material and poor morphology of species. Molecular genetic methods are necessary
      to verify the identification of these fungi. ITS1 or ITS2 region of rDNA alone is
      sufficient for correct identification. 

PMID- 26290004
TI  - alpha-Tocopherol Stereoisomers in Human Plasma Are Affected by the Level and Form
      of the Vitamin E Supplement Used.
AB  - BACKGROUND: Studies examining vitamin E intake and the percentage of the
      population meeting dietary guidelines do not distinguish between natural (RRR
      alpha-tocopherol) and synthetic (all-rac-alpha-tocopherol) intake, even though
      these different isomeric forms differ in bioactivity. OBJECTIVE: This study aimed
      to determine the effect of RRR-alpha-tocopherol vs. all-rac-alpha-tocopherol
      intake on the percentage of the population meeting the vitamin E recommendation
      and on plasma alpha-tocopherol stereoisomer distribution. METHODS: With the use
      of data from the Irish National Adult Nutrition Survey (NANS), this study
      examined the percentage of the Irish population meeting the European Union (EU)
      RDA for vitamin E of 12 mg/d, correcting for a bioactivity difference in all-rac-
      vs. RRR-alpha-tocopherol, where 1 mg of all-rac-alpha-tocopherol is considered to
      be equivalent to 1:1.36 (0.74) mg in the EU RDA. In a subcohort of supplement
      users and nonusers, plasma alpha- and gamma-tocopherol concentrations and alpha
      tocopherol stereoisomer distribution were measured. Receiver operating
      characteristic (ROC) curve analysis was conducted to determine ability to
      discriminate supplement user types. RESULTS: Analysis of the NANS showed that
      100% of participants still met the recommended intake of 12 mg/d, after all-rac
      alpha-tocopherol intake was corrected for alpha-tocopherol equivalent
      bioactivity. In the subcohort analysis, the percentage of plasma RRR-alpha
      tocopherol was significantly lower in high all-rac-alpha-tocopherol supplement
      (>11 mg/d) users (82%) compared with nonusers and with high RRR-alpha-tocopherol
      supplement (>35 mg/d) users (91% and 93% respectively, P < 0.01). High RRR-alpha
      tocopherol supplement users had a significantly higher plasma alpha-tocopherol
      than low all-rac-alpha-tocopherol supplement (<2.5 mg/d) users (34 vs. 25
      MUmol/L, P = 0.01). ROC analysis demonstrated an ability to distinguish between
      RRR- and all-rac-alpha-tocopherol consumers, which may be useful in investigating
      the potential effect of RRR- and all-rac-alpha-tocopherol intake on health.
      CONCLUSIONS: This study demonstrated that the percentage of the population
      meeting the vitamin E recommendation was unaffected when all-rac-alpha-tocopherol
      intake was corrected for alpha-tocopherol equivalent bioactivity. all-rac-alpha
      Tocopherol intake led to a decrease in the percentage of plasma RRR-alpha
      tocopherol relative to RRR-alpha-tocopherol intake.

PMID- 26290005
TI  - Early Breastfeeding Problems Mediate the Negative Association between Maternal
      Obesity and Exclusive Breastfeeding at 1 and 2 Months Postpartum.
AB  - BACKGROUND: Compared with normal-weight women, women with obesity experience
      poorer breastfeeding outcomes. Successful breastfeeding among women with obesity
      is important for achieving national breastfeeding goals. OBJECTIVES: The
      objectives were to determine whether the negative association between obesity and
      any or exclusive breastfeeding at 1 and 2 mo postpartum is mediated through
      breastfeeding problems that occur in the first 2 wk postpartum and if this
      association differs by parity. METHODS: Mothers (1151 normal-weight and 580
      obese) in the Infant Feeding Practices Study II provided information on
      sociodemographic and psychosocial characteristics, body mass index, and
      breastfeeding outcomes. At 1 mo postpartum, participants reported the
      breastfeeding problems they experienced in the first 2 wk postpartum from a
      predefined list of 17 options. We used factor analysis to condense these problems
      into 4 explanatory variables; continuous factor scores were computed for use in
      further analyses. We used maximum likelihood logistic regression to assess
      mediation of the association between obesity and breastfeeding outcomes through
      early breastfeeding problems. RESULTS: No significant effect of obesity was found
      on any breastfeeding at 1 or 2 mo. At 1 mo postpartum, for both primiparous and
      multiparous women, there was a significant direct effect of obesity on exclusive
      breastfeeding and a significant indirect effect of obesity through early
      breastfeeding problems related to the explanatory mediating variable
      "Insufficient Milk" (throughout the remainder of the Abstract, this factor will
      be denoted by upper case notation). At 2 mo postpartum both the direct effect of
      obesity and the indirect effect through Insufficient Milk were significant in
      primiparous women but only the indirect effect remained significant in
      multiparous women. CONCLUSIONS: Early problems related to Insufficient Milk may
      partially explain the association between obesity and poor exclusive
      breastfeeding outcomes. Women who are obese, particularly those reporting
      breastfeeding problems that grouped in the Insufficient Milk factor in the early
      postpartum period, may benefit from additional breastfeeding support.

PMID- 26290006
TI  - Maternal N-Carbamylglutamate Supplementation during Early Pregnancy Enhances
      Embryonic Survival and Development through Modulation of the Endometrial Proteome
      in Gilts.
AB  - BACKGROUND: Early pregnancy loss is a major concern in humans and animals. N
      carbamylglutamate (NCG) has been found to enhance embryonic survival during early
      pregnancy in rats. However, little is known about the key factors in the
      endometrium involved in the improvement of embryonic implantation and development
      induced by maternal NCG supplementation. OBJECTIVES: Our objectives were to
      investigate whether NCG supplementation during early gestation enhanced embryonic
      survival and development in gilts and to uncover the related factors using the
      approach of endometrium proteome analysis with isobaric tags for relative and
      absolute quantification (iTRAQ). METHODS: Uteruses and embryos/fetuses were
      obtained on days 14 and 28 of gestation from gilts fed a basal diet that was or
      was not supplemented with 0.05% NCG. The iTRAQ-based quantitative proteomics
      approach was performed to explore the endometrium proteome altered by NCG
      supplementation. RESULTS: Maternal NCG supplementation significantly increased
      the number of total fetuses and live fetuses on day 28 of gestation by 1.32 and
      1.29, respectively (P < 0.05), with a significant decrease in embryonic mortality
      (P < 0.05). iTRAQ results indicated that a total of 59 proteins showed at least 2
      fold differences (P < 0.05), including 52 proteins that were present at higher
      abundance and 7 proteins present at lower abundance in NCG-supplemented gilts.
      The differentially expressed proteins primarily are involved in cell adhesion,
      energy metabolism, lipid metabolism, protein metabolism, antioxidative stress,
      and immune response. On day 14 of gestation, several proteins closely related to
      embryonic implantation and development, such as integrin-alphav, integrin-beta3,
      talin, and endothelial nitric oxide synthase, were upregulated (3.7-, 4.1-, 2.4-,
      and 5.4-fold increases, respectively) by NCG supplementation. CONCLUSION: To our
      knowledge, our results provide the first evidence that altered abundance of the
      endometrial proteome induced by NCG supplementation is highly associated with the
      improvement of embryonic survival and development in gilts.

PMID- 26290007
TI  - The Nutrient Profile of Foods Consumed Using the British Food Standards Agency
      Nutrient Profiling System Is Associated with Metabolic Syndrome in the SU.VI.MAX
      Cohort.
AB  - BACKGROUND: Metabolic syndrome (MetS), comprising high waist circumference, blood
      pressure, glycemia, and triglycerides, and lower HDL cholesterol could in part be
      prevented by adequate nutrition. Nutrient profiling systems could be useful
      public health tools to help consumers make healthier food choices. An individual
      dietary index (DI) based on nutrient profiling of foods consumed could
      characterize dietary patterns in relation to the onset of MetS. OBJECTIVE: The
      objective of this study was to prospectively investigate the association between
      the Food Standards Agency (FSA) Nutrient Profiling System (NPS) DI and the onset
      of MetS in a middle-aged French cohort. METHODS: Participants from the
      SUpplementation en VItamines et Mineraux AntioXydants cohort (SU.VI.MAX, n =
      3741) were included in the present study. The FSA NPS DI was computed by using
      dietary data from 24 h records at inclusion. MetS was identified at baseline and
      at year 13 of follow-up with the use of self-reported medication, data from
      clinical investigations, and biological measurements. A prospective association
      between the FSA NPS DI (in quartiles and continuous) and the onset of MetS was
      investigated by using logistic regression. RESULTS: Poorer diets identified with
      the use of the FSA NPS DI were significantly associated with a higher risk of
      developing MetS (OR for poorer vs. healthier FSA NPS DI: 1.43; 95% CI: 1.08,
      1.89; P-trend across quartiles = 0.02). The FSA NPS DI was significantly
      associated with the systolic blood pressure (SBP) and diastolic blood pressure
      (DBP) components of MetS (difference between healthier vs. poorer FSA NPS DI:
      2.16 mm Hg for SBP and 1.5 mm Hg for DBP, P-trend across quartiles = 0.02).
      CONCLUSION: The FSA NPS DI was prospectively associated with the onset of MetS in
      a middle-aged French population. The application of NPSs in public health
      initiatives may help the population make healthier food choices, which might
      reduce the risk of developing MetS.

PMID- 26290008
TI  - High True Ileal Digestibility but Not Postprandial Utilization of Nitrogen from
      Bovine Meat Protein in Humans Is Moderately Decreased by High-Temperature, Long
      Duration Cooking.
AB  - BACKGROUND: Meat protein digestibility can be impaired because of indigestible
      protein aggregates that form during cooking. When the aggregates are subsequently
      fermented by the microbiota, they can generate potentially harmful compounds for
      the colonic mucosa. OBJECTIVE: This study evaluated the quantity of bovine meat
      protein escaping digestion in the human small intestine and the metabolic fate of
      exogenous nitrogen, depending on cooking processes. METHODS: Sixteen volunteers
      (5 women and 11 men; aged 28 +/- 8 y) were equipped with a double lumen
      intestinal tube positioned at the ileal level. They received a test meal
      exclusively composed of 120 g of intrinsically (15)N-labeled bovine meat, cooked
      either at 55 degrees C for 5 min (n = 8) or at 90 degrees C for 30 min (n = 8).
      Ileal effluents and blood and urine samples were collected over an 8-h period
      after the meal ingestion, and (15)N enrichments were measured to assess the
      digestibility of meat proteins and the transfer of dietary nitrogen into the
      metabolic pools. RESULTS: Proteins tended to be less digestible for the meat
      cooked at 90 degrees C for 30 min than at 55 degrees C for 5 min (90.1% +/- 2.1%
      vs. 94.1% +/- 0.7% of ingested N; P = 0.08). However, the particle number and
      size in ileal digesta did not differ between groups. The appearance of variable
      amounts of intact fibers was observed by microscopy. The kinetics of (15)N
      appearance in plasma proteins, amino acids, and urea were similar between groups.
      The amount of exogenous nitrogen lost through deamination did not differ between
      groups (21.2% +/- 0.8% of ingested N). CONCLUSIONS: Cooking bovine meat at a high
      temperature for a long time can moderately decrease protein digestibility
      compared with cooking at a lower temperature for a short time and does not affect
      postprandial exogenous protein metabolism in young adults. The study was
      registered at www.clinicaltrials.gov as NCT01685307.

PMID- 26290009
TI  - Consumption of Yogurt, Low-Fat Milk, and Other Low-Fat Dairy Products Is
      Associated with Lower Risk of Metabolic Syndrome Incidence in an Elderly
      Mediterranean Population.
AB  - BACKGROUND: The association between consumption of dairy products and the risk of
      developing metabolic syndrome (MetS) is unclear. OBJECTIVE: The purpose of this
      study was to evaluate the associations between consumption of dairy products
      (total and different subtypes) and incident MetS in a Mediterranean population at
      high cardiovascular disease risk. METHODS: We prospectively analyzed 1868 men and
      women (55-80 y old) without MetS at baseline, recruited from different PREDIMED
      (Prevencion con Dieta Mediterranea) centers between October 2003 and June 2009
      and followed up until December 2010. MetS was defined according to updated,
      harmonized criteria. At baseline and yearly thereafter, we determined
      anthropometric variables, dietary habits by a 137-item validated food-frequency
      questionnaire, and blood biochemistry. Multivariable-adjusted HRs of MetS or its
      components were estimated for each of the 2 upper tertiles (vs. the lowest one)
      of mean consumption of dairy products during the follow-up. RESULTS: During a
      median follow-up of 3.2 y, we documented 930 incident MetS cases. In the
      multivariable-adjusted model, HRs (95% CIs) of MetS for the comparison of extreme
      tertiles of dairy product consumption were 0.72 (0.61, 0.86) for low-fat dairy,
      0.73 (0.62, 0.86) for low-fat yogurt, 0.78 (0.66, 0.92) for whole-fat yogurt, and
      0.80 (0.67, 0.95) for low-fat milk. The respective HR for cheese was 1.31 (1.10,
      1.56). CONCLUSIONS: Higher consumption of low-fat dairy products, yogurt (total,
      low-fat, and whole-fat yogurt) and low-fat milk was associated with a reduced
      risk of MetS in individuals at high cardiovascular disease risk from a
      Mediterranean population. Conversely, higher consumption of cheese was related to
      a higher risk of MetS. This trial was registered at controlled-trials.com as
      ISRCTN35739639.

PMID- 26290010
TI  - An Integrated Predictive Model of Population Serum 25-Hydroxyvitamin D for
      Application in Strategy Development for Vitamin D Deficiency Prevention.
AB  - BACKGROUND: To enable food-based strategies for the prevention of vitamin D
      deficiency to be evidence-based, there is a need to develop integrated predictive
      models of population serum 25-hydroxyvitamin D [25(OH)D] that are responsive to
      both solar and dietary inputs of vitamin D. OBJECTIVES: The objectives of this
      work were to develop and validate an integrated mathematical model with the use
      of data on UVB availability, exposure, and dietary intake to predict serum
      25(OH)D concentrations in a nationally representative sample of adults, and then
      test the model's performance with the use of 3 hypothetical fortification
      scenarios as exemplars. METHODS: Data on UVB availability and hours of sunlight
      in Ireland were used in a mathematical model to predict serum 25(OH)D in Irish
      adults aged 18-64 y. An equation from our dose-related vitamin D supplementation
      trial in adults was developed and integrated into the model, which allowed us to
      predict the impact of changes in dietary vitamin D on the contribution to annual
      serum 25(OH)D concentrations, accounting for seasonality of UVB availability.
      Recently published estimates of the impact of 3 vitamin D food fortification
      scenarios on vitamin D intake in a representative sample of Irish adults were
      used in the model as a test. RESULTS: The UVB- and vitamin D intake-serum 25(OH)D
      components of the integrated model were both validated with the use of
      independent data. The model predicted that the percentage of vitamin D deficiency
      [serum 25(OH)D <30 nmol/L] in the adult population during an extended winter
      period was 18.1% (vs. 18.6% measured), which could be reduced in a stepwise
      manner with the incorporation of an increased number of vitamin D-fortified
      foods, down to 6.6% with the inclusion of enhanced fortified dairy-related
      products, fat spreads, fruit juice and drinks, and cereal products. CONCLUSION:
      Mathematical models have the ability to inform how vitamin D food fortification
      in various constructs may affect population serum 25(OH)D concentrations and the
      prevalence of vitamin D deficiency.

PMID- 26290011
TI  - Erratum to: Advantages of new technologies in oral mucosal surgery: an
      intraoperative comparison among Nd:YAG laser, quantic molecular resonance
      scalpel, and cold blade.

PMID- 26290012
TI  - Human 3beta-hydroxysteroid dehydrogenase deficiency seems to affect fertility but
      may not harbor a tumor risk: lesson from an experiment of nature.
AB  - CONTEXT: 3beta-hydroxysteroid dehydrogenase deficiency (3betaHSD) is a rare
      disorder of sexual development and steroidogenesis. There are two isozymes of
      3betaHSD, HSD3B1 and HSD3B2. Human mutations are known for the HSD3B2 gene which
      is expressed in the gonads and the adrenals. Little is known about testis
      histology, fertility and malignancy risk. OBJECTIVE: To describe the molecular
      genetics, the steroid biochemistry, the (immuno-)histochemistry and the clinical
      implications of a loss-of-function HSD3B2 mutation. METHODS: Biochemical, genetic
      and immunohistochemical investigations on human biomaterials. RESULTS: A 46,XY
      boy presented at birth with severe undervirilization of the external genitalia.
      Steroid profiling showed low steroid production for mineralocorticoids,
      glucocorticoids and sex steroids with typical precursor metabolites for HSD3B2
      deficiency. The genetic analysis of the HSD3B2 gene revealed a homozygous
      c.687del27 deletion. At pubertal age, he showed some virilization of the external
      genitalia and some sex steroid metabolites appeared likely through conversion of
      precursors secreted by the testis and converted by unaffected HSD3B1 in
      peripheral tissues. However, he also developed enlarged breasts through
      production of estrogens in the periphery. Testis histology in late puberty
      revealed primarily a Sertoli-cell-only pattern and only few tubules with arrested
      spermatogenesis, presence of few Leydig cells in stroma, but no neoplastic
      changes. CONCLUSIONS: The testis with HSD3B2 deficiency due to the c.687del27
      deletion does not express the defective protein. This patient is unlikely to be
      fertile and his risk for gonadal malignancy is low. Further studies are needed to
      obtain firm knowledge on malignancy risk for gonads harboring defects of androgen
      biosynthesis.

PMID- 26290013
TI  - Atrial Tachycardias Following Persistent Atrial Fibrillation Ablation: Predictors
      of Recurrence After the Repeat Ablation.
AB  - BACKGROUND: Repeat procedures after persistent atrial fibrillation (AF) ablation
      are frequently performed for secondary atrial tachycardias (AT). Predictors of AT
      recurrence after the first repeat ablation have not yet been studied. METHODS: We
      investigated predictors of AT recurrence in 117 patients who underwent ablation
      for secondary AT arising after a previous ablation for persistent AF using the
      Cox proportional hazards model. RESULTS: Acute ablation success rate was 94%.
      Over a follow-up period of 12 months, 61 patients (53%) were free from AT
      recurrence. Of the assessed predictors of AT recurrence, the number of ablated AT
      forms (>1 vs. 1) was significantly associated with AT recurrence (hazard ratio
      2.01, 95% CI 1.18-3.43, P = 0.01). Other variables including left atrial
      diameter, AT mechanism, or the characteristics of previous AF ablation did not
      have significant influence on AT recurrence (P>0.05). Men had a tendency toward
      fewer AT recurrences than women (OR 0.60, 95% CI 0.34-1.05, P = 0.07). During a
      second AT ablation procedure, 19 (49%) patients were identified to have a
      recurrence of the previously ablated AT, whereas in 20 patients (51%) a new AT
      form was diagnosed. CONCLUSION: Ablation of atrial tachycardias following
      persistent AF ablation has a high acute success rate. However, a substantial
      number of patients develop new onset AT during follow-up. The occurrence of
      multiple AT forms during the repeat ablation procedure was the only predictive
      factor for AT recurrence.

PMID- 26290014
TI  - The Contrasting Recognition Behavior of beta-Cyclodextrin and Its Sulfobutylether
      Derivative towards 4',6-Diamidino-2-phenylindole.
AB  - The noncovalent interactions between 4', 6-diamidino-2-phenylindole (DAPI) and
      sulfobutylether beta-cyclodextrin (SBE7beta-CD) are evaluated by using
      photochemical measurements and compared with that of native beta-CD. Contrasting
      recognition behavior and intriguing modulations in the photochemical behavior of
      DAPI were observed. In particular, a large enhancement in the fluorescence
      emission and excited-state lifetime were seen upon binding to SBE7beta-CD, with
      the SBE7beta-CD inclusion complex being approximately 1000 times stronger than
      that of beta-CD. The ensuing fluorescence "turn on" was demonstrated to be
      responsive to chemical stimuli, such as metal ions and adamantylanmine (AD). Upon
      addition of Ca(2+)/AD, nearly quantitative dissociation of the complex was
      established to regenerate the free dye and result in fluorescence "turn off". The
      SO3(-) groups are believed to be critical for the strong and selective binding of
      the chromophore and the stimuli-responsive tuning. This is as an important design
      criterion for the optimization of host-guest properties through supramolecular
      association, which is relevant for drug-delivery applications.

PMID- 26290015
TI  - Rechargeable Li-CO2 batteries with carbon nanotubes as air cathodes.
AB  - Rechargeable Li-CO2 batteries offer great promise by combining carbon capture and
      energy technology. However, the discharge product Li2CO3 is difficult to
      decompose upon recharging. In this work, carbon nanotubes (CNTs) with high
      electrical conductivity and porous three-dimensional networks were firstly
      explored as air cathodes for rechargeable Li-CO2 batteries. 

PMID- 26290017
TI  - [The future of patient-physician relationship].

PMID- 26290016
TI  - Gestational carrier BMI and reproductive, fetal and neonatal outcomes: are the
      risks the same with increasing obesity?
AB  - OBJECTIVE: Data suggest that female obesity impairs uterine receptivity and
      increases the risk of fetal and neonatal mortality. We analyzed the reproductive
      outcomes of gestational carriers (GCs) undergoing donated oocytes and assisted
      reproductive technology according to body mass index (BMI). DESIGN: A
      retrospective analysis of 163 GCs undergoing 226 in vitro fertilization (IVF) and
      embryo transfer cycles. METHODS: GCs undergoing in vitro fertilization and embryo
      transfer cycles were analyzed and divided according to their BMI (healthy weight:
      20-24.9 kg m(-2) (n=77 in 114 cycles); overweight: 25-29.9 kg m(-)(2) (n=55 in 71
      cycles); and obese: 30-35 kg m(-)(2) (n=31 in 41 cycles)). All GCs underwent a
      complete medical evaluation and were cleared for pregnancy before being selected.
      Overweight and obese GCs also underwent a metabolic screening, including an oral
      glucose tolerance test and lipid profile. The main outcomes measured were
      clinical pregnancy and live birth rates, antenatal and neonatal outcomes.
      RESULTS: Clinical pregnancy and live birth rates were similar despite increasing
      BMI. There were no statistically significant differences in the implantation
      rates, clinical pregnancy rates or live birth rates per embryo transfer among
      patients in the three BMI groups. In the healthy weight, overweight and obese
      GCs, the clinical pregnancy rates per GC were 72%, 84% and 79%, and per embryo
      transfer rates were 52%, 49% and 56%, respectively; P=NS. The live birth rates
      per GC were 70%, 84% and 75%, and per embryo transfer rates were 50%, 49% and
      53%, respectively; P=NS. Twin rates were similar between the groups (35%, 31% and
      29%, respectively; P=NS). There were no differences in gestational diabetes,
      preterm admissions or cesarean section rates. Neonatal intensive care unit
      admissions were similar (11%, 13% and 12%, respectively; P=NS), and no maternal,
      neonatal or infant mortality occurred. CONCLUSIONS: These data show that
      increasing obesity does not impair the reproductive outcome in GC cycles. Larger
      sample size is indicated to verify these findings. Furthermore, this study
      suggests that the standard metabolic screening used for GCs may lead to selection
      of healthier patients compared with women of comparable BMI who conceive outside
      of a fertility clinic setting, indicating the metabolic profile, rather than BMI,
      may better explain differences in pregnancy outcomes.

PMID- 26290018
TI  - [Insulin levels in teenagers with comedonal acne].
AB  - INTRODUCTION: Acne is considered a multifactorial skin disease secondary to an
      obstructive process of pilosebaceous units. Some studies suggest a relationship
      between insulin levels and the presence of acne, but this has not yet been
      demonstrated. OBJECTIVE: To compare the levels of insulin in patients with and
      without comedonal acne. MATERIAL AND METHODS: From January to July 2012, we
      conducted a cross-sectional study in the Dr. Ladislao de la Pascua Dermatologic
      Center in Mexico city. We recruited men and women from 14 to 25 years old with
      and without comedonal acne. We measured the insulin levels in all patients with
      DXI 800 Beckman Coulter equipment in a blood sample. RESULTS: Twenty patients
      with acne and 20 patients without acne were studied, with an average age of 17
      (+/-3) and 19 (+/-4) years, respectively. Both groups were different in terms of
      gender. Body mass index was similar in both groups. We did not find a difference
      in insulin levels between groups (p=0.818). The average level of insulin was
      7.15+/-4.7 uU/ml for the acne group and 7.85+/-3.3 uU/mL for the control group.
      CONCLUSION: Insulin levels are similar in patients with and without comedonal
      acne. There is no direct relationship between hyperinsulinemia and acne.

PMID- 26290019
TI  - [Level of stress and coping strategy in medical students compared with students
      of other careers].
AB  - OBJECTIVE: To assess the levels of stress and the coping strategies in students
      of the faculties of Medicine, Law and Psychology at a private university in Lima.
      MATERIALS AND METHODS: Cross-sectional analytic and comparative study involving
      three university careers. For data collection, the SISCO inventory for academic
      stress and the questionnaire of stress coping (CAE) were used. For inferential
      analysis, Spearman's rank correlation coefficient, Kruskall Wallis and Dunn Test
      (multiple comparison post hoc) were used. RESULTS: The average age was 19.5+/-2.5
      years. Of them, 33.9% were students from the Medical faculty and 92.4% were
      worried or nervous (stress manifestations). The students from the Medical faculty
      had the highest level of stress (median, 46.7) compared to the students from the
      Psychology faculty (median, 39.1) and the students from the Law faculty (median,
      40.2) (p<0.05). The most common coping strategies were focusing on the problem,
      positive re-evaluation, and social support. The least used strategy was religion.
      CONCLUSION: The Medical faculty students show the highest level of stress. Coping
      strategies in the three groups are focusing on the problem, positive re
      evaluation, and social support. The least used strategy was religion.

PMID- 26290020
TI  - [Domestic violence in patients and caregivers dyads in neurological diseases].
AB  - INTRODUCTION: Patients with neurological diseases are susceptible to abuse and
      neglect. Studies on violence in this context have mainly focused on abuse
      perpetrated by a caregiver to the patient directionally. In this study we
      describe violence in dyads of caregivers and patients with neurological disorders
      according to frequency, directionality, and type of relation. METHODS: One
      hundred-and-eighty-five caregiver-patient dyads were assessed by means of the
      National Survey of Violence Against Women (NSVAW) guidelines and the Zarit and
      Pfeiffer questionnaires. Bivariate analysis and Spearman correlation tests were
      performed. RESULTS: Violence was reported by 32.5% of caregivers and 33.5% of
      patients. In both groups, psychological abuse was the most common. Mutual
      violence (54.5%) is the most common type of abuse and the caregiver reported as
      having more violent behavior is the intimate partner. Epilepsy was the
      neurological disorder where violence was more prevalent (47.6%). CONCLUSIONS: The
      prevalence of violence in our sample is higher than the one for the general
      population of 21%, as reported by the NSVAW. Clinical neurologists and healthcare
      services are key elements for the detection of abuse in this context.

PMID- 26290021
TI  - [Cholesterol overload in hepatocytes affects nicotinamide adenine dinucleotide
      phosphate oxidase (NADPH) activity abrogating hepatocyte growth factor (HGF)
      induced cellular protection].
AB  - The increment in the prevalence of obesity incidence in Mexico is leading to the
      increase in many chronic maladies, including liver diseases. It is well known
      that lipid-induced liver sensitization is related to the kind of lipid rather
      than the amount of them in the organ. Cholesterol overload in the liver
      aggravates the toxic effects of canonical liver insults. However, the status on
      the repair and survival response elicited by nicotinamide adenine dinucleotide
      phosphate (NADPH) oxidase and the hepatocyte growth factor (HGF) is not
      completely understood. In the present, work we aimed to figure out the HGF/NADPH
      oxidase-induced cellular protection in the hepatocyte with a cholesterol
      overload. Our results show that a hypercholesterolemic diet induced liver damage
      and steatosis in mice. The hepatocytes isolated from these animals exhibited an
      increase in basal NADPH oxidase activity, although transcriptional levels of some
      of its components were decreased. No effect on the oxidase activity was observed
      in HGF treatments. The protective effect of HGF was abrogated as a result of
      cholesterol cellular overload, calculated by a survival assay. In conclusion, the
      cholesterol overload in hepatocytes impairs the HGF/NADPH oxidase-induced
      cellular protection. 

PMID- 26290022
TI  - [Evaluation of the results of percutaneous closure by means of the Amplatzer
      device in pediatric patients with intra-auricular communication (IAC)].
AB  - OBJECTIVE: To describe the results of percutaneous closure by means of the
      Amplatzer Septal Occluder (ASO) device in pediatric patients with intra-auricular
      communication (IAC). MATERIALS AND METHODS: Descriptive transversal study in
      patients submitted to percutaneous closure of IAC from March 2005 to March 2013.
      Patients aged <16 years, weight>6 kg, IAC type ostium segundum, and patent
      foramen ovale, with border separations borders>5 mm, and absence of coexisting
      pathology were included in the study. We excluded from the study children with
      severe pulmonary blood pressure/arterial hypertension. Descriptive statistics
      with the SPSS v. 20.0 statistical software package. RESULTS: We included in the
      study 28 patients, feminine gender (n=19, 68%), median age=8 years (range, 4-14),
      weight 30.7 kg (range, 15-69). New York Heart Association (NYHA) functional class
      I (n=21, 75%), II (n=7, 25%). Median IAC size, 15.50 mm (range, 5-25), and a
      median ASO size of 17.54 mm (range, 8-28). After ASO placement, 100% presented
      NYHA I at one month, cardiac murmur (n=2, 7.1%), cessation of cardiac murmur at
      month 6 (n=28, 100%), without evidence of arrhythmias at one month 100%, residual
      short circuit at 24 hours (n=4, 14%), complete occlusion at month 6 (n=28, 100%),
      normalization size of VD, and cessation of tricuspid insufficiency 100% at one
      year. Complications included minimal bleeding during the procedure (n=2, 7%),
      transitory cephalea (n=5, 18%), and dysautonomia (n=1, 4%). CONCLUSION:
      Percutaneous closure of IAC of children fitted with the ASO device is safe and
      exhibits good results.

PMID- 26290023
TI  - [Apa1 VDR polymorphism and osteoporosis risk in postmenopausal Mexican women].
AB  - AIM: To analyze the association between Apa1 VDR polymorphism and osteoporosis in
      Mexican mestizo postmenopausal women. METHODS: A cross-sectional study was
      conducted in 534 postmenopausal mestizo women from Mexico City to determine the
      association of the Apa1 Vitamin D Receptor gene polymorphism (rs7975232) with
      osteoporosis and osteoporosis plus fracture. Bone mineral density (BMD) was
      assessed using dual-energy X-ray absorptiometry. Genotyping was performed using
      real-time PCR with an allelic discrimination assay. RESULTS: The Apa1 allele
      frequencies were no different between groups. No association was found between
      Apa1 genotypes and osteoporosis (AA, OR: 1.08; 95% CI: 0.62-1.87; AC, OR: 0.70;
      95% CI: 0.45-1.07). Similar results were obtained for osteoporosis plus fracture
      (AA, OR: 0.93; 95% CI: 0.50-1.71; AC, OR: 0.70; 95% CI 0.45-1.07). After
      adjusting for age, the result remained. CONCLUSION: These findings are in
      agreement with previous studies reporting no association of Apa1 VDR polymorphism
      with osteoporosis.

PMID- 26290024
TI  - [Motivation and learning strategies in pediatric residents].
AB  - BACKGROUND: Motivation is an internal mood that moves individuals to act, points
      them in certain directions, and maintains them in activities, playing a very
      important role in self-regulated learning and academic performance. Our objective
      was to evaluate motivation and self-regulation of knowledge in pediatric
      residents in a third-level hospital, and to determine if there are differences
      according to the type of specialty and sociodemographic variables. MATERIAL AND
      METHODS: All residents who agreed to participate responded to the Motivated
      Strategies for Learning Questionnaire. Cronbach alpha was performed to determine
      reliability. The mean value of each subscale was compared with Student's t test
      or ANOVA, correlation of subscales with Pearson test. A value of p<=0.05 was
      considered significant. RESULTS: We included 118 residents. The questionnaire was
      highly reliable (alpha=0.939). There were no significant differences in
      motivation or learning strategies according to sex, marital status, or age. Those
      residents studying a second or third specialization had significantly higher
      scores in elaboration, critical thinking, and peer learning. There were
      significant correlations between intrinsic motivation and self-efficacy with the
      development of knowledge strategies such as elaboration, critical thinking, and
      metacognitive self-regulation. CONCLUSIONS: Our students present average-to-high
      scores of motivation and knowledge strategies, with a significant difference
      according to type of specialization. There is a high correlation between
      motivation and knowledge strategies.

PMID- 26290025
TI  - [Dental caries experience and its relation to oral hygiene in Mexican children].
AB  - INTRODUCTION: Dental caries is public health problem in Mexico and there are few
      studies on preschool children. OBJECTIVE: The aim of this study was to determine
      the caries experience in preschool children and its relation to oral hygiene in
      an underserved area of the state of Mexico. MATERIAL AND METHODS: A cross
      sectional, descriptive, observational and analytical study in children aged four
      and five years of age enrolled in children's centers. The sociodemographic
      variables were obtained through a questionnaire. Clinical evaluation of each of
      the infants was performed using the CPOD index for primary teeth caries , the
      criteria of the World Health Organization, and the significant caries index was
      calculated and oral hygiene was assessed using the criteria of the O'Leary index.
      Calibration was kappa>0.86 for indexes. RESULTS: The study population consisted
      of children of both genders: 69.5% had caries experience, and the index of
      decayed, missing, and filled teeth (DMFT) was 3.52+/-3.7 (d=3.37+/-3.5; m=0;
      f=0.11+/-0.51). The significant caries index was 8.95+/-0.39 (d=8.68+/-0.41;
      f=0.26+/-0.13). In total, 98.2% of children with caries experience had poor oral
      hygiene (DMFT: 4.91: 95% CI: 3.99-5.84), whereas in children with good hygiene it
      was 0.17 (95% CI: -0.18-0.51); existing association between caries experience and
      oral hygiene RM 913 (95% CI: 864-962; p<0.01). CONCLUSIONS: The caries experience
      of preschool children was high and was associated with poor oral hygiene
      affecting their dentition and usually is associated with caries in permanent
      dentition associated to social deprivation. Preventive programs are recommended
      from the first stage of life.

PMID- 26290026
TI  - [Involvement of phenotype secretor of senescent cells in the development of
      cancer, aging and the diseases associated with age].
AB  - Cellular senescence is defined as the physiological program of terminal growth
      arrest; in mammals it is an important tumor-suppressor mechanism since it stops
      premalignant cell proliferation. However, senescence also contributes to the
      decline associated to aging and the development of several diseases. This is
      explained by the fact that senescent cells secrete diverse molecules, which
      compromise the cellular microenvironment, and altogether are referred as
      senescent-associated secretory phenotype (SASP). The SASP is composed by
      cytokines, chemokines, growth factors, proteases, etc., whose function is to
      maintain the antiproliferative state and promote senescent cell clearance by the
      immune system. Nevertheless, over time, and particularly during old age, SASP
      might stimulate proliferation and premalignant cell transformation. The
      multifunctional roles of SASP would depend on the cell type and their
      physiological nature. Therefore, relying on the biological context, SASP could be
      beneficial and participate in the repair and regeneration processes, or
      detrimental and induce degenerative pathologies and cancer. 

PMID- 26290027
TI  - [Gene therapy for hereditary ophthalmological diseases: Advances and future
      perspectives].
AB  - Gene therapy is a promising new therapeutic strategy that could provide a novel
      and more effective way of targeting hereditary ophthalmological diseases. The eye
      is easily accessible, highly compartmentalized, and an immune-privileged organ
      that gives advantages as an ideal gene therapy target. Recently, important
      advances in the availability of various intraocular vector delivery routes and
      viral vectors that are able to efficiently transduce specific ocular cell types
      have been described. Gene therapy has advanced in some retinal inherited
      dystrophies; in this way, preliminary success is now being reported for the
      treatment of Leber congenital amaurosis (LCA). This review will provide an update
      in the field of gene therapy for the treatment of ocular inherited diseases. 

PMID- 26290028
TI  - [Toxic epidermal necrolysis and development of liver abscesses].
AB  - Pharmacologic hypersensitivities commonly express cutaneous manifestations, and
      the highest mortality is found in Stevens Johnson's syndrome and toxic epidermal
      necrolysis, mostly associated with antibiotics and anticonvulsive drugs. Toxic
      epidermal necrolysis is related in 80% of cases to pharmacologic hypersensitivity
      and systemic consequences may be found; hepatic injury has been described, but
      the finding of liver abscesses has not been reported among common injuries. The
      case of a patient with a rapid development of multiple liver abscesses in the
      clinical setting of hypersensitivity due to lamotrigine and the discussion of
      probable etiologies and management is presented. 

PMID- 26290029
TI  - [Mass-gathering medical strategies: The experience in the International Book Fair
      in Guadalajara].
AB  - INTRODUCTION: The Guadalajara International Book Fair (FIL) is a mass gathering,
      hosting publishing companies from 40 countries and more than 750,000 visitors. It
      is necessary to prioritize preventive measures focusing on earthquakes, fires,
      terrorist acts, and prevention of infections. The objective of this study is to
      describe and analyze the health problems encountered during FIL 2013 in order to
      improve civil protection services during future events. MATERIAL AND METHODS:
      Descriptive, cross-sectional study, collecting medical histories in accordance
      with Mexican Official Standard NOM-004-SSA3-2012, and classifying respondents
      into age groups. A total of 794 medical sheets for patients who received
      assistance at the Mobile Health Units were analyzed. RESULTS: Altogether, 794
      (0.1%) patients were medically evaluated out of 750,987 fair visitors during the
      study period. Of these, 32 patients were <12 years old; 111 were 13-20 years old;
      540 were 20-50 years old; and 111 were >50 years old. There were no complicated
      medical cases. A favorable impact of preventives strategies was observed.
      CONCLUSIONS: Non-complicated medical incidents were observed. It is necessary to
      increase the knowledge on health among the general public who attend this type of
      event. Training health professionals is a priority in prevention measures and
      providing care during mass events of this kind in Mexico's territory.

PMID- 26290030
TI  - [Diagnosis and treatment approach for necrotizing scleritis (NS): A clinical
      case].
AB  - Necrotizing scleritis is an immune-mediated ocular inflammatory process,
      characterized by an area of avascular necrosis and a profound inflammation of the
      sclera and episclera. Necrotizing scleritis and its association with peripheral
      ulcerative keratitis--necrotizing sclerokeratitis (NS)--represents a serious
      threat for vision and eye integrity, evolves very fast if untreated, and its
      finding suggests the presence of a potentially lethal systemic vasculitic
      process. The following case is an example of the diagnostic approach and
      therapeutic scale in a 63-year-old women with necrotizing sclerokeratitis.

PMID- 26290031
TI  - [Pinch-off syndrome. Case report and review of the literature].
AB  - Central venous catheterization is a common procedure in the emergency and
      intensive-care units. Rupture of the central catheter has been described as a
      rare complication in patients with permanent subclavian catheters. We report the
      case of a patient with rupture and central catheter and embolization secondary to
      intermittent mechanical compression by the subclavian and the first rib (pinch
      off syndrome) and its resolution through a percutaneous device. 

PMID- 26290032
TI  - [Cutaneous metastasis of renal cell carcinoma: A case report and review of the
      literature].
AB  - INTRODUCTION: Renal cell carcinoma (RCC) accounts for 2-3% of adult solid
      malignancies. About 25-30% develop metastasis at the time of diagnosis and 60%
      corresponds to clear cell type. CASE PRESENTATION: A 66-year-old man, with a
      personal history of left radical nephrectomy, presents with an asymptomatic skin
      tumor he noticed one month earlier. Histopathologic study reported metastatic
      cutaneous infiltration of clear cell carcinoma, suggestive of a primary renal
      carcinoma. DISCUSSION: Cutaneous metastasis of RCC represents 6.0-6.8% of all
      cutaneous metastases. These patients have poor prognosis and, therefore, their
      treatment is palliative. It is essential to perform a complete periodic
      dermatologic examination for proper restaging and treatment.

PMID- 26290033
TI  - [Elena de Cespedes: The eventful life of a XVI century surgeon].
AB  - Throughout the history of surgery there have been exceptional cases of surgeons
      around the world. One of them is Elena/o of Cespedes. Born as a girl, this
      hermaphrodite dedicated all his life to acting as a man, doing jobs that were
      only for men such as a soldier, peasant, and surgeon. She was the first licensed
      surgeon in Spain and maybe in all Europe. She married a woman and then was tried
      for sodomy by the Spanish Inquisition commanded by inquisitor Lope de Mendoza.
      She was founded guilty and punished with 200 lashes and a 10-year service at a
      hospital, dressed as a woman. 

PMID- 26290034
TI  - [Andres Vesalio, Francisco Diaz, Miguel de Cervantes Saavedra and the birth of
      urology in the 16th Century].
AB  - In the sixteenth century there were great advances in science, literature, and
      the arts. During this century, urology as a specialty was conceived, thanks to
      the contributions of Andreas Vesalius, anatomist and leading physician to the
      court of Charles V, and Dr. Francisco Diaz, a native of Alcala de Henares,
      surgeon and clinician. Dr. Diaz had a close relationship with Miguel de
      Cervantes, who at one point in his life suffered from renal colic. In his
      masterpiece "Re-Printed Treaty of all diseases of the kidneys, bladder and
      wattles of the Cock and Urina, divided into three books," of which the first book
      of urology is the History of Medicine, describes in detail the clinical and
      therapeutic aspects of urological diseases, known as the "bad stone" and urethral
      strictures known as "wattles", in addition to describing the different surgical
      techniques and the development of new instruments for urological procedures,
      which include the cisorio instrument and the Speculum pudendi. For the above, Dr.
      Francisco Diaz is considered the father of urology. 

PMID- 26290035
TI  - [History and progress of trachea transplantation in Mexico].
AB  - Central airway obstruction and particularly tracheal stenosis is a clinical
      problem where definite resolution is a tracheal resection, evaluating the
      magnitude, length, and ventilatory compromise of patient. The resectable fragment
      is limited to 30% of the total length in children, or 6 cm in adults with
      terminal end anastomosis. The replacement of longer sections through allogeneic
      transplantation has been disappointing due to the unfeasibility of the organ,
      rejection of the graft, and the highly complicated surgical procedure. Tissue
      bioengineering has designed the replacement of functional organs generated in
      vitro in the short term, with the absence of immunological responses to the
      graft. This is based on a non-biological matrix where epithelial and mesenchymal
      cells are planted in such a matrix. In this document, we review the history and
      development of trachea transplantation in Mexico as well as the application of
      these new technologies in the context of its world development, which is a
      reality in other countries as a new alternative in obstructive illness of the
      airway. 

PMID- 26290036
TI  - [Answer: Indice de Saturacion Modificado (ISM) in emergency rooms. Another index
      else?].

PMID- 26290037
TI  - Nematic Liquid Crystal on a Two Dimensional Hexagonal Lattice and its
      Application.
AB  - We have studied the alignment of liquid crystal adsorbed onto graphene and
      hexagonal boron nitride by using a polarized optical microscope. From the
      experimental data, it was found that there were 6 different alignment
      orientations of the liquid crystal molecules on a single crystal substrate. This
      result has never been reported and is quite different from other previous
      results. As the hexagonal lattice has a threefold rotational symmetry, three
      different alignment orientations were expected, but our result seems counter
      intuitive. We explain this result considering the bending of the tail of the
      liquid crystal molecules. Using this anchoring effect with six accurate discrete
      angles, a novel non-volatile display can be developed with micron-scale pixel
      size, due to the molecular level accuracy of the alignment. 

PMID- 26290038
TI  - Effect of sexual diary keeping and self-evaluation on female sexual function and
      depression: A pilot study.
AB  - OBJECTIVES: The aim of the trial was to assess the effect of self-evaluation and
      sexual diary keeping on female sexual function and depressive symptoms in women
      diagnosed with sexual dysfunction. METHODS: A single-arm non-randomised trial
      included 30 women (53 +/- 7 years of age) with female sexual dysfunction (Female
      Sexual Function Index [FSFI] < 27) and a stable partnership duration of 5-40
      years. Female sexual function was assessed by sexual, psychological and
      gynaecological history taking and validated questionnaires including the FSFI,
      Female Sexual Distress Scale (FSDS) and Hamilton Depression Scale (HDS), before
      and after 4 weeks of sexual diary keeping. RESULTS: A subjective improvement in
      communication of sexual problems was reported by 60% of participants; no
      participants reported any worsening of communication. FSFI and FSDS scores were,
      respectively, 18.0 +/- 7.7 and 22.0 +/- 10.0 at baseline and 20.2 +/- 7.2 and
      20.6 +/- 11.5 after 4 weeks. HDS score decreased from 6.0 +/- 4.0 at baseline to
      4.4 +/- 2.7 after 4 weeks (p = 0.042). CONCLUSIONS: Self-evaluation and sexual
      diary keeping may improve aspects of sexual life, such as couple communication,
      without a direct effect on variables measured with validated questionnaires on
      different domains of sexual function.

PMID- 26290040
TI  - Carboxyl-Assisted Synthesis of Nitrogen-Doped Graphene Sheets for Supercapacitor
      Applications.
AB  - The high ratio of pyridinic and pyridone N-doped graphene sheets have been
      synthesized by functionalizing graphene oxide (GO) with different oxygen groups
      on its surface. The typical N-doped graphene was determined to be ~3-5 layers by
      transmission electron microscopy (TEM) and atomic force microscopy (AFM), and the
      nitrogen content was measured as 6.8-8 at. % by X-ray photoelectron spectroscopy
      (XPS). The structure of the N-doped graphene with different surface functional
      groups was characterized by Raman spectroscopy. The research result indicates
      that the carboxylation of GO is the key factor to obtain pyridinic and pyridone N
      types during the N atom doping process. Compared to general N-doped graphene, the
      electrochemical test shows that specific capacitance of the GO-OOH-N sample
      reaches up to 217 F/g at a discharge current density 1 A/g and stable cycling
      performance (keep 88.8 % specific capacitance after 500 cycles at the same
      discharge current density) when applied to the supercapacitor electrode
      materials. 

PMID- 26290039
TI  - Early pathogenesis of Duchenne muscular dystrophy modelled in patient-derived
      human induced pluripotent stem cells.
AB  - Duchenne muscular dystrophy (DMD) is a progressive and fatal muscle degenerating
      disease caused by a dystrophin deficiency. Effective suppression of the primary
      pathology observed in DMD is critical for treatment. Patient-derived human
      induced pluripotent stem cells (hiPSCs) are a promising tool for drug discovery.
      Here, we report an in vitro evaluation system for a DMD therapy using hiPSCs that
      recapitulate the primary pathology and can be used for DMD drug screening.
      Skeletal myotubes generated from hiPSCs are intact, which allows them to be used
      to model the initial pathology of DMD in vitro. Induced control and DMD myotubes
      were morphologically and physiologically comparable. However, electric
      stimulation of these myotubes for in vitro contraction caused pronounced calcium
      ion (Ca(2+)) influx only in DMD myocytes. Restoration of dystrophin by the exon
      skipping technique suppressed this Ca(2+) overflow and reduced the secretion of
      creatine kinase (CK) in DMD myotubes. These results suggest that the early
      pathogenesis of DMD can be effectively modelled in skeletal myotubes induced from
      patient-derived iPSCs, thereby enabling the development and evaluation of novel
      drugs. 

PMID- 26290041
TI  - Development and Applications of Lectins as Biological Tools in Biomedical
      Research.
AB  - As a new and burgeoning area following genomics and proteomics, glycomics has
      become a hot issue due to its pivotal roles in many physiological and
      pathological processes. Glycans are much more complicated than genes or proteins
      since glycans are highly branched and dynamic. Antibodies and lectins are the two
      major molecular tools applied for glycan profiling. Though the study of
      antibodies and lectins started at almost the same time in 1880s, lectins gained
      much less attention than the antibodies until recent decades when the importance
      and difficulties of glycomics were realized. The present review summarizes the
      discovery history of lectins and their biological functions with a special
      emphasis on their various applications as biological tools. Both older techniques
      that had been developed in the last century and new technologies developed in
      recent years, especially lectin microarrays and lectin-based biosensors, are
      included in this account. 

PMID- 26290042
TI  - Does heart rate variability reflect the systemic inflammatory response in a fetal
      sheep model of lipopolysaccharide-induced sepsis?
AB  - Fetal inflammatory response occurs during chorioamnionitis, a frequent and often
      subclinical inflammation associated with increased risk for brain injury and life
      lasting neurologic deficits. No means of early detection exist. We hypothesized
      that systemic fetal inflammation without septic shock will be reflected in
      alterations of fetal heart rate (FHR) variability (fHRV) distinguishing baseline
      versus inflammatory response states. In chronically instrumented near-term fetal
      sheep (n = 24), we induced an inflammatory response with lipopolysaccharide (LPS)
      injected intravenously (n = 14). Ten additional fetuses served as controls. We
      measured fetal plasma inflammatory cytokine IL-6 at baseline, 1, 3, 6, 24 and 48
      h. 44 fHRV measures were determined continuously every 5 min using continuous
      individualized multi-organ variability analysis (CIMVA). CIMVA creates an fHRV
      measures matrix across five signal-analytical domains, thus describing
      complementary properties of fHRV. Using principal component analysis (PCA), a
      widely used technique for dimensionality reduction, we derived and quantitatively
      compared the CIMVA fHRV PCA signatures of inflammatory response in LPS and
      control groups. In the LPS group, IL-6 peaked at 3 h. In parallel, PCA-derived
      fHRV composite measures revealed a significant difference between LPS and control
      group at different time points. For the LPS group, a sharp increase compared to
      baseline levels was observed between 3 h and 6 h, and then abating to baseline
      levels, thus tracking closely the IL-6 inflammatory profile. This pattern was not
      observed in the control group. We also show that a preselection of fHRV measures
      prior to the PCA can potentially increase the difference between LPS and control
      groups, as early as 1 h post LPS injection. We propose a fHRV composite measure
      that correlates well with levels of inflammation and tracks well its temporal
      profile. Our results highlight the potential role of HRV to study and monitor the
      inflammatory response non-invasively over time.

PMID- 26290043
TI  - Anticancer properties and enhancement of therapeutic potential of cisplatin by
      leaf extract of Zanthoxylum armatum DC.
AB  - BACKGROUND: Clinical use of chemotherapeutic drug, cisplatin is limited by its
      toxicity and drug resistance. Therefore, efforts continue for the discovery of
      novel combination therapies with cisplatin, to increase efficacy and reduce its
      toxicity. Here, we screened 16 medicinal plant extracts from Northeast part of
      India and found that leaf extract of Zanthoxylum armatum DC. (ZALE) induced
      cytotoxicity as well as an effect on the increasing of the efficiency of
      chemotherapeutic drugs (cisplatin, mitomycin C and camptothecin). This work shows
      detail molecular mechanism of anti-cancer activity of ZALE and its potential for
      combined treatment regimens to enhance the apoptotic response of chemotherapeutic
      drugs. RESULTS: ZALE induced cytotoxicity, nuclear blebbing and DNA fragmentation
      in HeLA cells suggesting apoptosis induction in human cervical cell line.
      However, the apoptosis induced was independent of caspase 3 activation and poly
      ADP ribose polymerase (PARP) cleavage. Further, ZALE activated Mitogen-activated
      protein kinases (MAPK) pathway as revealed by increased phosphorylation of
      extracellular-signal-regulated kinases (ERK), p38 and c-Jun N-terminal kinase
      (JNK). Inhibition of ERK activation but not p38 or JNK completely blocked the
      ZALE induced apoptosis suggesting an ERK dependent apoptosis. Moreover, ZALE
      generated DNA double strand breaks as suggested by the induction gammaH2AX foci
      formation. Interestingly, pretreatment of certain cancer cell lines with ZALE,
      sensitized the cancer cells to cisplatin and other chemotherapeutic drugs.
      Enhanced caspase activation was observed in the synergistic interaction among
      chemotherapeutic drugs and ZALE. CONCLUSION: Purification and identification of
      the bio-active molecules from the ZALE or as a complementary treatment for a
      sequential treatment of ZALE with chemotherapeutic drugs might be a new
      challenger to open a new therapeutic window for the novel anti-cancer treatment.

PMID- 26290045
TI  - The investigation of EEG specificity in epileptic children during Depakine
      therapy.
AB  - BACKGROUND: Antiepileptic drug (AED) therapy in epileptic children can be
      optimized via an anticipation of AED efficacy during early stages of therapy. We
      hypothesize that the comprehensive electroencephalography (EEG) evaluation can
      determine AED efficacy in epileptic children. Thus, this study aimed to
      investigate the alteration of characteristics of interictal EEG during the AED
      therapy. METHODS: Forty-three children aged 3-9 were investigated. EEGs were
      recorded three times: prior to valproic acid-Depakine (Dep) monotherapy and twice
      under the Dep therapy (at three and six/eight months). Baseline EEG was analyzed
      for quantitative characteristics of interictal EEG, such as absolute values of
      the power (AVP) spectra and EEG topography/brain mapping. The study involved
      epileptiform EEG and clinical condition assessments. RESULTS: Dep decreased AVP
      spectra in a low-frequency range, suppressed spontaneous epileptic discharge, and
      spike-wave complex 3/s. Dep partially decreased spikes-polyspikes, sharp waves,
      and generalized paroxysmal bursts during functional trials. Dep did not diminish
      rhythmic monomorphic theta-waves (RMT) of tempo-parietal localization observed by
      brain mapping. The presence of RMT correlated with the reocurrence of seizures if
      Dep was withdrawn. CONCLUSIONS: The findings of this study suggest that the
      presence of RMT with tempo-parietal localization on the interictal EEG can
      anticipate reocurrence of seizures if Dep dose will be reduced or withdrawn. The
      efficacy of the AED therapy can be revealed via reduction of low-frequency waves
      and suppression of epileptiform EEG elements parallel to clinical improvement.
      Thus, optimal treatment strategies can be tailored based on the evaluation of
      background EEG characteristics using spectral analysis, EEG mapping, and the
      quantitative EEG approach.

PMID- 26290044
TI  - Comparative effectiveness and tolerance of treatments for Helicobacter pylori:
      systematic review and network meta-analysis.
AB  - OBJECTIVE: To determine the most efficacious treatment for eradication of
      Helicobacter pylori with the lowest likelihood of some common adverse events
      among pre-recommended and newer treatment regimens. DESIGN: Systematic review and
      network meta-analysis. DATA SOURCES: Cochrane Library, PubMed, and Embase without
      language or date restrictions. STUDY SELECTION: Full text reports of randomised
      controlled trials that compared different eradication treatments for H pylori
      among adults. RESULTS: Of the 15,565 studies identified, 143 were eligible and
      included. Data on 14 kinds of treatments were available. Of 91 possible
      comparisons for the efficacy outcome, 34 were compared directly and the following
      treatments performed better: seven days of concomitant treatment (proton pump
      inhibitor and three kinds of antibiotics administered together), 10 or 14 days of
      concomitant treatment, 10 or 14 days of probiotic supplemented triple treatment
      (standard triple treatment which is probiotic supplemented), 10 or 14 days of
      levofloxacin based triple treatment (proton pump inhibitor, levofloxacin, and
      antibiotic administered together), 14 days of hybrid treatment (proton pump
      inhibitor and amoxicillin used for seven days, followed by a proton pump
      inhibitor, amoxicillin, clarithromycin, and 5-nitroimidazole for another seven
      days), and 10 or 14 days of sequential treatment (five or seven days of a proton
      pump inhibitor plus amoxicillin, followed by five or seven additional days of a
      proton pump inhibitor plus clarithromycin and 5-nitroimidazole or amoxicillin).
      In terms of tolerance, all treatments were considered tolerable, but seven days
      of probiotic supplemented triple treatment and seven days of levofloxacin based
      triple treatment ranked best in terms of the proportion of adverse events
      reported. CONCLUSION: Comparison of different eradication treatments for H pylori
      showed that concomitant treatments, 10 or 14 days of probiotic supplemented
      triple treatment, 10 or 14 days of levofloxacin based triple treatment, 14 days
      of hybrid treatment, and 10 or 14 days of sequential treatment might be better
      alternatives for the eradication of H pylori.

PMID- 26290046
TI  - The contribution of sport participation to overall health enhancing physical
      activity levels in Australia: a population-based study.
AB  - BACKGROUND: The contribution of sport to overall health-enhancing leisure-time
      physical activity (HELPA) in adults is not well understood. The aim was to
      examine this in a national sample of Australians aged 15+ years, and to extend
      this examination to other ostensibly sport-associated activities. METHODS: The
      2010 Exercise, Recreation and Sport Survey (ERASS) was conducted by telephone
      interview in four quarterly waves. Data from this survey were analysed to
      categorise leisure-time physical activity (LTPA) as HELPA or non-HELPA, and to
      categorise HELPA activities and sessions of HELPA activity by setting and
      frequency. The contribution of sport to HELPA was estimated, both directly
      through activities and settings classified as sport per se, and indirectly
      through other fitness activities ostensibly related to preparation for sport and
      enhancement of sport performance. RESULTS: Of 21,602 respondents, 82 % reported
      some LTPA in the 12 months prior to the survey. In aggregate, respondents
      reported 37,020 activity types in the previous 12 months, of which 94 % were
      HELPA. Of HELPA activities, 71 % were non-organised, 11 % were organised but not
      sport club-based, and 18 % were sport club-based. Of all sport activities, 52 %
      were HELPA. Of sport HELPA, 33 % was sport club-based and 78 % was undertaken
      >=12 times/year. Sport club members were significantly more likely to have
      participated in running, but significantly less likely to have participated in
      walking or aerobics/fitness training, than non-club members. CONCLUSIONS: Club
      sport participation contributes considerably to LTPA at health enhancing levels.
      Health promotion policies, and more specifically physical activity policies,
      should emphasize the role of sport in enhancing health. Sport policy should
      recognise the health-promoting role of community-based sport in addition to the
      current predominant focus on elite pathways.

PMID- 26290047
TI  - A non-healing lesion in a 14-year old boy with primary immunodeficiency: a rare
      case of actinic keratosis affecting a child.

PMID- 26290048
TI  - Activation of GLP-1 and gastrin signalling induces in vivo reprogramming of
      pancreatic exocrine cells into beta cells in mice.
AB  - AIMS/HYPOTHESIS: Lineage conversion of non-beta cells into insulin-producing
      cells has been proposed as a therapy for the cure of diabetes. Glucagon-like
      peptide-1 (GLP-1) and its derivatives can induce beta cell neogenesis in vitro
      and beta cell mass expansion in vivo, but GLP-1 signalling has not been shown to
      regulate cell fate decisions in vivo. We therefore tested the impact of GLP-1
      receptor (GLP1R) expression on beta cell differentiation in vivo. METHODS: Mice
      overexpressing GLP1R in pancreatic exocrine cells were generated by Cre-mediated
      recombination in sex-determining region Y-box 9 (SOX9)-expressing cells and then
      treated with exendin-4 and/or gastrin. Histological analysis was performed to
      detect cellular reprogramming from the exocrine lineage into insulin-producing
      cells. RESULTS: Whereas no newly generated beta cells were detected in the mice
      treated with exendin-4 alone, treatment with gastrin only induced the conversion
      of exocrine cells into insulin-producing cells. Furthermore, the overexpression
      of GLP1R, together with gastrin and exendin-4, synergistically promoted beta cell
      neogenesis accompanied by the formation of islet-like clusters. These newly
      generated beta cells expressed beta cell specific transcription factors, such as
      pancreatic and duodenal homeobox 1 (PDX1), NK6 homeobox 1 (NKX6.1) and
      musculoaponeurotic fibrosarcoma oncogene family A (MafA). These mice showed no
      histological evidence of pancreatitis or pancreatic dysplasia in their acini and
      had normal plasma amylase levels. CONCLUSIONS/INTERPRETATION: Activation of GLP-1
      and gastrin signalling induces beta cell neogenesis in the exocrine lineage
      without any deleterious pancreatic changes, which may lead to a potential therapy
      to cure diabetes by generating surrogate beta cells.

PMID- 26290049
TI  - Elevated HbA(1c) levels and the accumulation of differentiated T cells in CMV(+)
      individuals.
AB  - AIMS/HYPOTHESIS: Biological ageing of the immune system, or immunosenescence,
      predicts poor health and increased mortality. A hallmark of immunosenescence is
      the accumulation of differentiated cytotoxic T cells (CD27(-)CD45RA(+/-); or
      dCTLs), partially driven by infection with the cytomegalovirus (CMV). Immune
      impairments reminiscent of immunosenescence are also observed in hyperglycaemia,
      and in vitro studies have illustrated mechanisms by which elevated glucose can
      lead to increased dCTLs. This study explored associations between glucose
      dysregulation and markers of immunosenescence in CMV(+) and CMV(-) individuals.
      METHODS: A cross-sectional sample of participants from an occupational cohort
      study (n = 1,103, mean age 40 years, 88% male) were assessed for HbA(1c) and
      fasting glucose levels, diabetes, cardiovascular risk factors (e.g. lipids),
      numbers of circulating effector memory (EM; CD27(-)CD45RA(-)) and CD45RA re
      expressing effector memory (EMRA; CD27(-)CD45RA(+)) T cells, and CMV infection
      status. Self-report and physical examination assessed anthropometric,
      sociodemographic and lifestyle factors. RESULTS: Among CMV(+) individuals (n =
      400), elevated HbA(1c) was associated with increased numbers of EM (B = 2.75, p <
      0.01) and EMRA (B = 2.90, p < 0.01) T cells, which was robust to adjustment for
      age, sex, sociodemographic variables and lifestyle factors. Elevated EM T cells
      were also positively associated with total cholesterol (B = 0.04, p < 0.05) after
      applying similar adjustments. No associations were observed in CMV(-)
      individuals. CONCLUSIONS/INTERPRETATION: The present study identified consistent
      associations of unfavourable glucose and lipid profiles with accumulation of
      dCTLs in CMV(+) individuals. These results provide evidence that the impact of
      metabolic risk factors on immunity and health can be co-determined by infectious
      factors, and provide a novel pathway linking metabolic risk factors with
      accelerated immunosenescence.

PMID- 26290050
TI  - First multicenter study on multidrug resistant bacteria carriage in Chinese ICUs.
AB  - BACKGROUND: The importance of multidrug-resistant organisms (MDRO) in Chinese
      hospitals is not clearly delineated. Thus we sought to assess the prevalence of
      MDRO in Chinese intensive care units (ICUs). METHODS: Prospective study of
      inpatients admitted consecutively to eight ICUs in four Chinese cities in 2009
      10. Admission and weekly screenings were performed by using selective media for
      methicillin resistant Staphylococcus aureus, extended-spectrum beta-lactamase
      producing Enterobacteriaceae, Acinetobacter and Pseudomonas aeruginosa. For the
      two latters, resistance to ceftazidime defined MDRO. Backward logistic regression
      models were designed to assess factors independently associated with MDRO
      carriage on admission and MDRO acquisition within ICUs. RESULTS: 686 patients
      were included, and the MDRO prevalence rate on admission was 30.5 % (32.7 % for
      ESBL-positive Enterobacteriaceae, 3.2 % for MRSA). Antibiotic treatment prior to
      ICU admission was independently associated with carriage on admission (OR: 1.4)
      in multivariate analysis. A total of 104 patients acquired >=1 MDRO in ICU
      (overall attack rate: 23.7 %; 14.9 % for ESBL-positive Enterobacteriaceae, and
      5.1 % for MRSA). The MDRO attack rate increased from 13.2 % in the first week to
      82.1 % for ICU stay > 3 weeks. Duration of antibiotic exposure (OR: 1.16; 1.1
      1.2) and prior antibiotic treatment before ICU (OR: 2.1; 1.1-3.3) were associated
      with MDRO acquisition in multivariate analysis. The MDRO prevalence rate on ICU
      discharge was 51.2 % and the global prevalence density rate 71 per 1000 hospital
      days. CONCLUSION: More than one out of two patients was MDRO carrier on ICU
      discharge in Chinese hospitals. This is the result of the combination of a high
      MDRO prevalence rate on ICU admission and a high MDRO acquisition rate within
      ICU.

PMID- 26290052
TI  - Quantitative analysis of velopharyngeal movement using a stereoendoscope:
      accuracy and reliability of range images.
AB  - OBJECTIVE: We developed a novel method of producing accurate range images of the
      velopharynx using a three-dimensional (3D) endoscope to obtain detailed
      measurements of velopharyngeal movements. The purpose of the present study was to
      determine the relationship between the distance from the endoscope to an object,
      elucidate the measurement accuracy along the temporal axes, and determine the
      degree of blurring when using a jig to fix the endoscope. METHODS: An endoscopic
      measuring system was developed in which a pattern projection system was
      incorporated into a commercially available 3D endoscope. After correcting the
      distortion of the camera images, range images were produced using pattern
      projection to achieve stereo matching. Graph paper was used to measure the
      appropriate distance from the camera to an object, the mesial buccal cusp of the
      right maxillary first molar was measured to clarify the range image stability,
      and an electric actuator was used to evaluate the measurement accuracy along the
      temporal axes. RESULTS: The measurement error was substantial when the distance
      from the camera to the subject was >6.5 cm. The standard error of the 3D
      coordinate value produced from 30 frames was within 0.1 mm (range, 0.01-0.08 mm).
      The measurement error of the temporal axes was 9.16% in the horizontal direction
      and 9.27% in the vertical direction. CONCLUSION: The optimal distance from the
      camera to an object is <6.5 cm. The present endoscopic measuring system can
      provide stable range images of the velopharynx when using an appropriate fixation
      method and enables quantitative analysis of velopharyngeal movements.

PMID- 26290051
TI  - Developmental Cognitive Neuroscience of Adolescent Sexual Risk and Alcohol Use.
AB  - Human adolescents engage in very high rates of unprotected sex. This behavior has
      a high potential for unintended, serious, and sustained health consequences
      including HIV/AIDS. Despite these serious health consequences, we know little
      about the neural and cognitive factors that influence adolescents' decision
      making around sex, and their potential overlap with behaviorally co-occurring
      risk behaviors, including alcohol use. Thus, in this review, we evaluate the
      developmental neuroscience of sexual risk and alcohol use for human adolescents
      with an eye to relevant prevention and intervention implications. 

PMID- 26290053
TI  - Chromatographic methods for the isolation, separation and characterisation of
      dissolved organic matter.
AB  - This review presents an overview of the separation techniques applied to the
      complex challenge of dissolved organic matter characterisation. The review
      discusses methods for isolation of dissolved organic matter from natural waters,
      and the range of separation techniques used to further fractionate this complex
      material. The review covers both liquid and gas chromatographic techniques, in
      their various modes, and electrophoretic based approaches. For each, the
      challenges that the separation and fractionation of such an immensely complex
      sample poses is critically reviewed. 

PMID- 26290054
TI  - Thermal and Photolytic Transformation of NHC-B,N-Heterocycles: Controlled
      Generation of Blue Fluorescent 1,3-Azaborinine Derivatives and 1H-Imidazo[1,2
      a]indoles by External Stimuli.
AB  - NHC-B,N-heterocyclic compounds have been found to act as convenient precursors
      for obtaining either 1,3-azaborinine or 1H-imidazo[1,2-a]indole derivatives,
      which are two different and rare classes of compounds. The formation of these two
      classes of compounds from the NHC-B,N-heterocycles is highly selective depending
      on the external stimuli employed, and the resulting products have been studied
      for their interesting chemical and photophysical properties. The mechanism and
      possible reaction pathways of the unusual transformation are established by
      computational studies. 

PMID- 26290055
TI  - The new stimulant designer compound pentedrone exhibits rewarding properties and
      affects dopaminergic activity.
AB  - Cathinone derivatives are new recreational drugs known to produce psychostimulant
      effects. However, unlike other psychostimulants, the addictive potential of
      cathinone derivatives has not been widely studied. Here, we investigated the
      effects of pentedrone, a type of cathinone derivative, on the dopaminergic system
      using reverse transcription polymerase chain reaction and Western blot. We also
      evaluated the addictive potential of pentedrone using conditioned place
      preference and self-administration. We found that pentedrone increased the mRNA
      expression of dopamine 1 receptor, dopamine 2 receptor and dopamine transporter,
      as well as induced phosphorylation of cAMP response element-binding protein in PC
      12 cells. Additionally, pentedrone at 3 and 10 mg/kg significantly increased
      conditioned place preference in mice, while pentedrone at 0.3 mg/kg/infusion
      significantly increased self-administration in rats. Finally, we found that acute
      administration of pentedrone enhanced locomotor activity in a dose-dependent
      manner. Collectively, these data suggest that the addictive properties of
      pentedrone may be due to its effects on the dopaminergic system.

PMID- 26290057
TI  - Non-uniform sampling: post-Fourier era of NMR data collection and processing.
AB  - The invention of multidimensional techniques in the 1970s revolutionized NMR,
      making it the general tool of structural analysis of molecules and materials. In
      the most straightforward approach, the signal sampling in the indirect dimensions
      of a multidimensional experiment is performed in the same manner as in the direct
      dimension, i.e. with a grid of equally spaced points. This results in lengthy
      experiments with a resolution often far from optimum. To circumvent this problem,
      numerous sparse-sampling techniques have been developed in the last three
      decades, including two traditionally distinct approaches: the radial sampling and
      non-uniform sampling. This mini review discusses the sparse signal sampling and
      reconstruction techniques from the point of view of an underdetermined linear
      algebra problem that arises when a full, equally spaced set of sampled points is
      replaced with sparse sampling. Additional assumptions that are introduced to
      solve the problem, as well as the shape of the undersampled Fourier transform
      operator (visualized as so-called point spread function), are shown to be the
      main differences between various sparse-sampling methods.

PMID- 26290056
TI  - Low-threshold amplified spontaneous emission and lasing from colloidal
      nanocrystals of caesium lead halide perovskites.
AB  - Metal halide semiconductors with perovskite crystal structures have recently
      emerged as highly promising optoelectronic materials. Despite the recent surge of
      reports on microcrystalline, thin-film and bulk single-crystalline metal halides,
      very little is known about the photophysics of metal halides in the form of
      uniform, size-tunable nanocrystals. Here we report low-threshold amplified
      spontaneous emission and lasing from ~10 nm monodisperse colloidal nanocrystals
      of caesium lead halide perovskites CsPbX3 (X=Cl, Br or I, or mixed Cl/Br and Br/I
      systems). We find that room-temperature optical amplification can be obtained in
      the entire visible spectral range (440-700 nm) with low pump thresholds down to
      5+/-1 MUJ cm(-2) and high values of modal net gain of at least 450+/-30 cm(-1).
      Two kinds of lasing modes are successfully observed: whispering-gallery-mode
      lasing using silica microspheres as high-finesse resonators, conformally coated
      with CsPbX3 nanocrystals and random lasing in films of CsPbX3 nanocrystals. 

PMID- 26290058
TI  - Damped oscillations in a multiple delayed feedback NF-kappaB signaling module.
AB  - The NF-[Formula: see text]B signaling system regulates a number of cellular
      processes. Recent studies with simplified models found a damped function of the
      dual delayed feedback NF-kappaB signaling module. We use a computational model to
      investigate how multiple delayed feedback aids achieving damping oscillation in
      the system and how internal noise can influence the damping function. A curve
      fitting method (CFM) is introduced to quantify the damped oscillation. Our
      results show that (1) the structure of multiple delayed feedback, containing
      double or triple significantly delayed feedback, determines achieving damped
      oscillation. (2) Internal noise could aid the system to achieve damped
      oscillation under almost all circumstances.

PMID- 26290059
TI  - Statistical thermodynamics of transcription profiles in normal development and
      tumorigeneses in cohorts of patients.
AB  - Experimental biology is providing the distribution of numerous different
      biological molecules inside cells and in body fluids of patients. Statistical
      methods of analysis have very successfully examined these rather large databases.
      We seek to use a thermodynamic analysis to provide a physical understanding and
      quantitative characterization of human cancers and other pathologies within a
      molecule-centered approach. The key technical development is the introduction of
      a Lagrangian. By imposing constraints the minimal value of the Lagrangian defines
      a thermodynamically stable state of the cellular system. The minimization also
      allows using experimental data measured at a number of different conditions to
      evaluate the steady-state distribution of biomolecules such as messenger RNAs.
      Thereby the number of effectively accessible quantum states of biomolecules is
      determined from the experimentally measured expression levels. With the increased
      resolution provided by the minimization of the Lagrangian one can differentiate
      between normal and diseased patients and further between disease subtypes. Each
      such refinement corresponds to imposing an additional constraint of biological
      origin. The constraints are the unbalanced ongoing biological processes in the
      system. MicroRNA expression level data for control and diseased lung cancer
      patients are analyzed as an example. 

PMID- 26290060
TI  - Arginine-, D-arginine-vasopressin, and their inverso analogues in micellar and
      liposomic models of cell membrane: CD, NMR, and molecular dynamics studies.
AB  - We describe the synthesis, pharmacological properties, and structures of
      antidiuretic agonists, arginine vasopressin (AVP) and [D-Arg(8)]-vasopressin
      (DAVP), and their inverso analogues. The structures of the peptides are studied
      based on micellar and liposomic models of cell membranes using CD spectroscopy.
      Additionally, three-dimensional structures in mixed anionic-zwitterionic micelles
      are obtained using NMR spectroscopy and molecular dynamics simulations. NMR data
      have shown that AVP and DAVP tend to adopt typical of vasopressin-like peptides
      beta-turns: in the 2-5 and 3-6 fragments. The inverso-analogues also adopt beta
      turns in the 3-6 fragments. For this reason, their inactivity seems to be due to
      the difference in side chains orientations of Tyr(2), Phe(3), and Arg(8),
      important for interactions with the receptors. Again, the potent antidiuretic
      activity of DAVP can be explained by CD data suggesting differences in mutual
      arrangement of the aromatic side chains of Tyr(2) and Phe(3) in this peptide in
      liposomes rather than of native AVP. In the presence of liposomes, the smallest
      conformational changes of the peptides are noticed with DPPC and the largest with
      DPPG liposomes. This suggests that electrostatic interactions are crucial for the
      peptide-membrane interactions. We obtained similar, probably active,
      conformations of the antidiuretic agonists in the mixed DPC/SDS micelles (5:1)
      and in the mixed DPPC/DPPG (7:3) liposomes. Thus it can be speculated that the
      anionic-zwitterionic liposomes as well as the anionic-zwitterionic micelles,
      mimicking the eukaryotic cell membrane environment, partially restrict
      conformational freedom of the peptides and probably induce conformations
      resembling those of biologically relevant ones. 

PMID- 26290061
TI  - Ten years of change in clinical disease status and treatment in rheumatoid
      arthritis: results based on standardized monitoring of patients in an ordinary
      outpatient clinic in southern Norway.
AB  - INTRODUCTION: In the new millennium, clinical outcomes in patients with
      rheumatoid arthritis (RA) have improved. Despite a large number of register data,
      there is a lack of data reflecting the entire outpatient RA population, and in
      particular long-term data. The main aim of this study was to explore changes in
      clinical disease status and treatment in an RA outpatient clinic population
      monitored with recommended outcome measures over a 10-year period. METHODS:
      Standard data collected included demographic data, erythrocyte sedimentation
      rate, C-reactive protein, clinical measures of disease activity (Disease Activity
      Score in 28 joint counts [DAS28], Clinical Disease Activity Index [CDAI],
      Simplified Disease Activity Index [SDAI] and global assessments) and patient
      reported outcomes (measures of physical function, joint pain, fatigue, patient
      global assessment and morning stiffness). Treatment with disease-modifying
      antirheumatic drugs (DMARDs) was also recorded, as well as rheumatoid factor (RF)
      and anti-citrullinated protein antibody (ACPA) status. RESULTS: In the RA
      population, the mean age was approximately 64 years and disease duration was 10
      12 years. About 70 % were females; approximately 20 % were current smokers; and
      65-70 % were positive for RF and ACPA. During follow-up, disease activity
      improved significantly. When we applied the DAS28, CDAI, SDAI and Boolean
      criteria for remission, the proportions of patients in remission increased from
      21.3 %, 8.1 %, 5.8 % and 3.8 %, respectively, in 2004 to 55.5 %, 31.7 %, 31.8 %
      and 17.7 %, respectively, in 2013. The proportions of patients with DAS28, CDAI
      and SDAI low disease activity status were 16.0 %, 34.0 %, and 34.9 %,
      respectively, in 2004 and 17.8 %, 50.4 % and 50.8 %, respectively, in 2013. A
      significant improvement in patient-reported outcome was seen only for the full 10
      years, but not for the last 4 years, of the study period. The proportion of
      patients taking synthetic (about 60 %) and biologic (approximately 30 %) DMARDs
      was stable over the last 4 years of the study period, with no significant change
      observed, whereas the proportion of patients being treated with prednisolone was
      reduced significantly from 61 % in 2010 to 54 % in 2013. CONCLUSIONS: The
      encouraging data we present suggest that the vast majority of patients with RA
      monitored in outpatient clinics in the new millennium can expect to achieve a
      status of clinical remission or low disease activity.

PMID- 26290062
TI  - Imaging the Phase Separation Between PEDOT and Polyelectrolytes During Processing
      of Highly Conductive PEDOT:PSS Films.
AB  - Treating PEDOT: PSS (Clevios) with certain additives, such as ethylene glycol
      (EG), dimethyl sulfoxide (DMSO) and sorbitol, has been shown to increase the
      conductivity of this material from roughly 1 to nearly 1000 S/cm. Using a slow
      drying method, we show that the additive induced a separation between free PSS
      and reorganized PEDOT: PSS complexes in the highly conductive PEDOT: PSS films.
      Additives (DMSO, DEG, and PEG 400) were included in PEDOT: PSS aqueous
      dispersions at large volume fractions. The mixtures were slowly dried under room
      conditions. During drying, the evaporation of water resulted in an additive-rich
      solvent mixture from which the reorganized PEDOT: PSS complexes aggregated into a
      dense film while free PSS remained in the solution. Upon complete drying, PSS
      formed a transparent rim film around the conducting PEDOT film. The chemical
      compositions of the two phases were studied using an infrared microscope. This
      removal of PSS resulted in more compact packing of PEDOT molecules, as confirmed
      by X-ray diffraction measurements. X-ray photoelectron spectroscopy and atomic
      force microscope measurements suggested the enrichment of PEDOT on the film
      surface after PSS separation. Through a simple drying process in an additive
      containing dispersion, the conductivity of PEDOT films increased from 0.1 to 200
      400 S/cm. Through this method, we confirmed the existence of two phases in
      additive-treated and highly conductive PEDOT: PSS films. The proper separation
      between PSS and PEDOT will be of relevance in designing strategies to process
      high-performance plastic electrodes.

PMID- 26290063
TI  - Adolescence as a unique developmental period.

PMID- 26290064
TI  - Topiramate augmentation in a patient with obsessive-compulsive disorder.

PMID- 26290065
TI  - Altered pain threshold sensitivity and frontoparietal-cingulate network in
      anorexia nervosa: the role of disgust sensitivity.

PMID- 26290066
TI  - Altered pain threshold sensitivity and frontoparietal-cingulate network in
      anorexia nervosa: the role of disgust sensitivity--Author response.

PMID- 26290067
TI  - Early evolutionary history and genomic features of gene duplicates in the human
      genome.
AB  - BACKGROUND: Human gene duplicates have been the focus of intense research since
      the development of array-based and targeted next-generation sequencing approaches
      in the last decade. These studies have primarily concentrated on determining the
      extant copy-number variation from a population-genomic perspective but lack a
      robust evolutionary framework to elucidate the early structural and genomic
      characteristics of gene duplicates at emergence and their subsequent evolution
      with increasing age. RESULTS: We analyzed 184 gene duplicate pairs comprising
      small gene families in the draft human genome with 10% or less synonymous
      sequence divergence. Human gene duplicates primarily originate from DNA-mediated
      events, taking up genomic residence as intrachromosomal copies in direct or
      inverse orientation. The distribution of paralogs on autosomes follows random
      expectations in contrast to their significant enrichment on the sex chromosomes.
      Furthermore, human gene duplicates exhibit a skewed gradient of distribution
      along the chromosomal length with significant clustering in pericentromeric
      regions. Surprisingly, despite the large average length of human genes, the
      majority of extant duplicates (83%) are complete duplicates, wherein the entire
      ORF of the ancestral copy was duplicated. The preponderance of complete
      duplicates is in accord with an extremely large median duplication span of 36 kb,
      which enhances the probability of capturing ancestral ORFs in their entirety.
      With increasing evolutionary age, human paralogs exhibit declines in (i) the
      frequency of intrachromosomal paralogs, and (ii) the proportion of complete
      duplicates. These changes may reflect lower survival rates of certain classes of
      duplicates and/or the role of purifying selection. Duplications arising from RNA
      mediated events comprise a small fraction (11.4%) of all human paralogs and are
      more numerous in older evolutionary cohorts of duplicates. CONCLUSIONS: The
      degree of structural resemblance, genomic location and duplication span appear to
      influence the long-term maintenance of paralogs in the human genome. The median
      duplication span in the human genome far exceeds that in C. elegans and yeast and
      likely contributes to the high prevalence of complete duplicates relative to
      structurally heterogeneous duplicates (partial and chimeric). The relative roles
      of regulatory sequence versus exon-intron structure changes in the acquisition of
      novel function by human paralogs remains to be determined.

PMID- 26290068
TI  - Mental health service use by recent immigrants from different world regions and
      by non-immigrants in Ontario, Canada: a cross-sectional study.
AB  - BACKGROUND: Given that immigration has been linked to a variety of mental health
      stressors, understanding use of mental health services by immigrant groups is
      particularly important. However, very little research on immigrants' use of
      mental health service in the host country considers source country. Newcomers
      from different source countries may have distinct experiences that influence
      service need and use after arrival. This population study examined rates of use
      of primary care and of specialty services for non-psychotic mental health
      disorders by immigrants to Ontario Canada during their first five years after
      arrival. Service use by recent immigrants in broad source region groups
      representing all world regions was compared to use by age-matched Canadian-born
      or long term immigrants (called long term residents). METHOD: This matched
      population-based cross-sectional study assessed likelihood of any use and counts
      of visits for each of primary care, psychiatric care and hospital care (emergency
      department visits or inpatient admissions) for non-psychotic mental health
      disorders from 1993-2012. Adult immigrants living in urban Ontario (n = 912,114)
      were categorized based on their nine world regions of origin. Sex-stratified
      conditional logistic regression models and negative binomial models were used to
      compare service use by immigrant region groups to their age-matched long term
      residents. RESULTS: Immigrant were more or less likely to access primary mental
      health care compared to age-matched long term residents, depending on their world
      region of origin. Regarding specialty mental health care (psychiatry and hospital
      care), immigrants from all regions used less than long term residents. Across the
      three mental health services, estimates of use by immigrant region groups
      compared to long term residents were among the lowest for newcomers from East
      Asian and Pacific (range: 0.16-0.82) and among the highest for persons from
      Middle East and North Africa (range: 0.56-1.23). CONCLUSION: This population
      based study showed lower use of mental health services by recent immigrants than
      long-term immigrants or native born individuals, with variation in immigrants'
      use linked to world region of origin and type of mental health care. Variation
      across source region groups underscores the importance of identifying underlying
      individual characteristics that affect service use to make services more
      responsive to newcomers.

PMID- 26290069
TI  - A study on a robot arm driven by three-dimensional trajectories predicted from
      non-invasive neural signals.
AB  - BACKGROUND: A brain-machine interface (BMI) should be able to help people with
      disabilities by replacing their lost motor functions. To replace lost functions,
      robot arms have been developed that are controlled by invasive neural signals.
      Although invasive neural signals have a high spatial resolution, non-invasive
      neural signals are valuable because they provide an interface without surgery.
      Thus, various researchers have developed robot arms driven by non-invasive neural
      signals. However, robot arm control based on the imagined trajectory of a human
      hand can be more intuitive for patients. In this study, therefore, an integrated
      robot arm-gripper system (IRAGS) that is driven by three-dimensional (3D) hand
      trajectories predicted from non-invasive neural signals was developed and
      verified. METHODS: The IRAGS was developed by integrating a six-degree of freedom
      robot arm and adaptive robot gripper. The system was used to perform reaching and
      grasping motions for verification. The non-invasive neural signals,
      magnetoencephalography (MEG) and electroencephalography (EEG), were obtained to
      control the system. The 3D trajectories were predicted by multiple linear
      regressions. A target sphere was placed at the terminal point of the real
      trajectories, and the system was commanded to grasp the target at the terminal
      point of the predicted trajectories. RESULTS: The average correlation coefficient
      between the predicted and real trajectories in the MEG case was [Formula: see
      text] ([Formula: see text]). In the EEG case, it was [Formula: see text]
      ([Formula: see text]). The success rates in grasping the target plastic sphere
      were 18.75 and 7.50 % with MEG and EEG, respectively. The success rates of
      touching the target were 52.50 and 58.75 % respectively. CONCLUSIONS: A robot arm
      driven by 3D trajectories predicted from non-invasive neural signals was
      implemented, and reaching and grasping motions were performed. In most cases, the
      robot closely approached the target, but the success rate was not very high
      because the non-invasive neural signal is less accurate. However the success rate
      could be sufficiently improved for practical applications by using additional
      sensors. Robot arm control based on hand trajectories predicted from EEG would
      allow for portability, and the performance with EEG was comparable to that with
      MEG.

PMID- 26290070
TI  - The evolutionary puzzle of egg size, oxygenation and parental care in aquatic
      environments.
AB  - Offspring fitness generally improves with increasing egg size. Yet, eggs of most
      aquatic organisms are small. A common but largely untested assumption is that
      larger embryos require more oxygen than they can acquire through diffusion via
      the egg surface, constraining egg size evolution. However, we found no
      detrimental effects of large egg size on embryo growth and survival under hypoxic
      conditions. We tested this in the broad-nosed pipefish, Syngnathus typhle, whose
      males provide extensive care (nourishment, osmoregulation and oxygenation) to
      their young in a brood pouch on their bodies. We took advantage of this species'
      pronounced variation in egg size, correlating positively with female size, and
      tested the effect of hypoxia (40% dissolved oxygen) versus fully oxygenated
      (100%) water on embryo size and survival of large versus small eggs after 18 days
      of paternal brooding. Egg size did not affect embryo survival, regardless of O2
      treatment. While hypoxia affected embryo size negatively, both large and small
      eggs showed similar reductions in growth. Males in hypoxia ventilated more and
      males with large eggs swam more, but neither treatment affected their position in
      the water column. Overall, our results call into question the most common
      explanation for constrained egg size evolution in aquatic environments. 

PMID- 26290072
TI  - Resolving the life cycle alters expected impacts of climate change.
AB  - Recent models predict contrasting impacts of climate change on tropical and
      temperate species, but these models ignore how environmental stress and
      organismal tolerance change during the life cycle. For example, geographical
      ranges and extinction risks have been inferred from thermal constraints on
      activity during the adult stage. Yet, most animals pass through a sessile
      embryonic stage before reaching adulthood, making them more susceptible to
      warming climates than current models would suggest. By projecting microclimates
      at high spatio-temporal resolution and measuring thermal tolerances of embryos,
      we developed a life cycle model of population dynamics for North American
      lizards. Our analyses show that previous models dramatically underestimate the
      demographic impacts of climate change. A predicted loss of fitness in 2% of the
      USA by 2100 became 35% when considering embryonic performance in response to
      hourly fluctuations in soil temperature. Most lethal events would have been
      overlooked if we had ignored thermal stress during embryonic development or had
      averaged temperatures over time. Therefore, accurate forecasts require detailed
      knowledge of environmental conditions and thermal tolerances throughout the life
      cycle. 

PMID- 26290071
TI  - Interpreting melanin-based coloration through deep time: a critical review.
AB  - Colour, derived primarily from melanin and/or carotenoid pigments, is integral to
      many aspects of behaviour in living vertebrates, including social signalling,
      sexual display and crypsis. Thus, identifying biochromes in extinct animals can
      shed light on the acquisition and evolution of these biological traits. Both
      eumelanin and melanin-containing cellular organelles (melanosomes) are preserved
      in fossils, but recognizing traces of ancient melanin-based coloration is fraught
      with interpretative ambiguity, especially when observations are based on
      morphological evidence alone. Assigning microbodies (or, more often reported,
      their 'mouldic impressions') as melanosome traces without adequately excluding a
      bacterial origin is also problematic because microbes are pervasive and
      intimately involved in organismal degradation. Additionally, some forms
      synthesize melanin. In this review, we survey both vertebrate and microbial
      melanization, and explore the conflicts influencing assessment of microbodies
      preserved in association with ancient animal soft tissues. We discuss the types
      of data used to interpret fossil melanosomes and evaluate whether these are
      sufficient for definitive diagnosis. Finally, we outline an integrated
      morphological and geochemical approach for detecting endogenous pigment remains
      and associated microstructures in multimillion-year-old fossils. 

PMID- 26290073
TI  - Hidden impacts of ocean acidification to live and dead coral framework.
AB  - Cold-water corals, such as Lophelia pertusa, are key habitat-forming organisms
      found throughout the world's oceans to 3000 m deep. The complex three-dimensional
      framework made by these vulnerable marine ecosystems support high biodiversity
      and commercially important species. Given their importance, a key question is how
      both the living and the dead framework will fare under projected climate change.
      Here, we demonstrate that over 12 months L. pertusa can physiologically acclimate
      to increased CO2, showing sustained net calcification. However, their new
      skeletal structure changes and exhibits decreased crystallographic and molecular
      scale bonding organization. Although physiological acclimatization was evident,
      we also demonstrate that there is a negative correlation between increasing CO2
      levels and breaking strength of exposed framework (approx. 20-30% weaker after 12
      months), meaning the exposed bases of reefs will be less effective 'load
      bearers', and will become more susceptible to bioerosion and mechanical damage by
      2100. 

PMID- 26290074
TI  - Hummingbird tongues are elastic micropumps.
AB  - Pumping is a vital natural process, imitated by humans for thousands of years. We
      demonstrate that a hitherto undocumented mechanism of fluid transport pumps
      nectar onto the hummingbird tongue. Using high-speed cameras, we filmed the
      tongue-fluid interaction in 18 hummingbird species, from seven of the nine main
      hummingbird clades. During the offloading of the nectar inside the bill,
      hummingbirds compress their tongues upon extrusion; the compressed tongue remains
      flattened until it contacts the nectar. After contact with the nectar surface,
      the tongue reshapes filling entirely with nectar; we did not observe the
      formation of menisci required for the operation of capillarity during this
      process. We show that the tongue works as an elastic micropump; fluid at the tip
      is driven into the tongue's grooves by forces resulting from re-expansion of a
      collapsed section. This work falsifies the long-standing idea that capillarity is
      an important force filling hummingbird tongue grooves during nectar feeding. The
      expansive filling mechanism we report in this paper recruits elastic recovery
      properties of the groove walls to load nectar into the tongue an order of
      magnitude faster than capillarity could. Such fast filling allows hummingbirds to
      extract nectar at higher rates than predicted by capillarity-based foraging
      models, in agreement with their fast licking rates. 

PMID- 26290075
TI  - Spreading of healthy mood in adolescent social networks.
AB  - Depression is a major public health concern worldwide. There is evidence that
      social support and befriending influence mental health, and an improved
      understanding of the social processes that drive depression has the potential to
      bring significant public health benefits. We investigate transmission of mood on
      a social network of adolescents, allowing flexibility in our model by making no
      prior assumption as to whether it is low mood or healthy mood that spreads. Here,
      we show that while depression does not spread, healthy mood among friends is
      associated with significantly reduced risk of developing and increased chance of
      recovering from depression. We found that this spreading of healthy mood can be
      captured using a non-linear complex contagion model. Having sufficient friends
      with healthy mood can halve the probability of developing, or double the
      probability of recovering from, depression over a 6-12-month period on an
      adolescent social network. Our results suggest that promotion of friendship
      between adolescents can reduce both incidence and prevalence of depression. 

PMID- 26290076
TI  - A size threshold governs Caenorhabditis elegans developmental progression.
AB  - The growth of organisms from humans to bacteria is affected by environmental
      conditions. However, mechanisms governing growth and size control are not well
      understood, particularly in the context of changes in food availability in
      developing multicellular organisms. Here, we use a novel microfluidic platform to
      study the impact of diet on the growth and development of the nematode
      Caenorhabditis elegans. This device allows us to observe individual worms
      throughout larval development, quantify their growth as well as pinpoint the
      moulting transitions marking successive developmental stages. Under conditions of
      low food availability, worms grow very slowly, but do not moult until they have
      achieved a threshold size. The time spent in larval stages can be extended by
      over an order of magnitude, in agreement with a simple threshold size model.
      Thus, a critical worm size appears to trigger developmental progression, and may
      contribute to prolonged lifespan under dietary restriction. 

PMID- 26290077
TI  - Selection analysis on the rapid evolution of a secondary sexual trait.
AB  - Evolutionary analyses of population translocations (experimental or accidental)
      have been important in demonstrating speed of evolution because they subject
      organisms to abrupt environmental changes that create an episode of selection.
      However, the strength of selection in such studies is rarely measured, limiting
      our understanding of the evolutionary process. This contrasts with long-term,
      mark-recapture studies of unmanipulated populations that measure selection
      directly, yet rarely reveal evolutionary change. Here, we present a study of
      experimental evolution of male colour in Trinidadian guppies where we tracked
      both evolutionary change and individual-based measures of selection. Guppies were
      translocated from a predator-rich to a low-predation environment within the same
      stream system. We used a combination of common garden experiments and monthly
      sampling of individuals to measure the phenotypic and genetic divergence of male
      coloration between ancestral and derived fish. Results show rapid evolutionary
      increases in orange coloration in both populations (1 year or three generations),
      replicating the results of previous studies. Unlike previous studies, we linked
      this evolution to an individual-based analysis of selection. By quantifying
      individual reproductive success and survival, we show, for the first time, that
      males with more orange and black pigment have higher reproductive success, but
      males with more black pigment also have higher risk of mortality. The net effect
      of selection is thus an advantage of orange but not black coloration, as
      reflected in the evolutionary response. This highlights the importance of
      considering all components of fitness when understanding the evolution of
      sexually selected traits in the wild.

PMID- 26290078
TI  - Differential expression of micrornas in porcine parvovirus infected porcine cell
      line.
AB  - BACKGROUND: Porcine parvovirus (PPV), a member of the Parvoviridae family, causes
      great economic loss in the swine industry worldwide. MicroRNAs (miRNAs) are a
      class of non-protein-coding genes that play many diverse and complex roles in
      viral infections. FINDING: Aiming to determine the impact of PPV infections on
      the cellular miRNAome, we used high-throughput sequencing to sequence two miRNA
      libraries prepared from porcine kidney 15 (PK-15) cells under normal conditions
      and during PPV infection. There was differential miRNA expression between the
      uninfected and infected cells: 65 miRNAs were upregulated and 128 miRNAs were
      downregulated. We detected the expression of miR-10b, miR-20a, miR-19b, miR-181a,
      miR-146b, miR-18a, and other previously identified immune-related miRNAs. Gene
      Ontology analysis and KEGG function annotations of the host target genes
      suggested that the miRNAs are involved in complex cellular pathways, including
      cellular metabolic processes, immune system processes, and gene expression.
      CONCLUSIONS: These data suggest that a large group of miRNAs is expressed in PK
      15 cells and that some miRNAs were altered in PPV-infected PK-15 cells. A number
      of microRNAs play an important role in regulating immune-related gene expression.
      Our findings should help with the development of new control strategies to
      prevent or treat PPV infections in swine.

PMID- 26290079
TI  - Synthesis, Characterization and Screening for Analgesic and Anti-inflammatory
      activities of 2, 5-disubstituted 1, 3, 4-oxadiazole derivatives.
AB  - The aim of the present investigation was to synthesize, characterize and evaluate
      analgesic and anti- inflammatory activities of 2, 5-disubstituted 1, 3, 4
      oxadiazole derivatives. The reaction of starting material 4-chloro-m-cresol with
      ethyl chloroacetate in dry acetone affords ethyl (4-chloro-3-methylphenoxy)
      acetate, which after reacting with the hydrazine hydrate in ethanol yields 2(4
      chloro-3-methylphenoxy) acetohydrazide. When 2(4-chloro-3-methylphenoxy)
      acetohydrazide was treated with different aromatic aldehydes, aromatic acids and
      carbon disulfide in alcoholic solution, different 3-acetyl-5-[(4-chloro-3
      methylphenoxy) methyl]-2-aryl-2, 3-dihydro-1, 3, 4-oxadiazole and 2-[(4-chloro-3
      methylphenoxy) methyl]-5-aryl-1, 3, 4-oxadiazole derivatives were obtained.
      Purity of the derivatives was confirmed by thin layer chromatography and melting
      point. Structure of these derivatives was set up by determining infrared
      spectroscopy, nuclear magnetic resonance spectroscopy and mass spectroscopy.
      Further, the synthesized derivatives were evaluated for their analgesic and anti
      inflammatory activities in rodents. In animal studies, the derivatives 3-acetyl-5
      [(4-chloro-3- methylphenoxy)methyl]-2-(4-methoxyphenyl)-2,3-dihydro-1, 3, 4
      oxadiazole and 4-{5-[(4-chloro-3- methylphenoxy)methyl]-1, 3, 4-oxadiazol-2
      yl}pyridine show more potent analgesic activity and the derivatives 2-{3-acetyl-5
      [(4-chloro-3-methylphenoxy)methyl]-2,3-dihydro-1, 3, 4-oxadiazol-2-yl}phenol and
      3-acetyl-5- [(4-chloro-3-methylphenoxy)methyl]-2-(4-methoxyphenyl)-2,3-dihydro-1,
      3, 4-oxadiazole exhibit more potent anti-inflammatory effect as compared to other
      derivatives. The results of the current study indicate that cyclization of
      acetohydrazide produces novel oxadiazole derivatives with potent analgesic and
      anti-inflammatory activities. 

PMID- 26290080
TI  - The Antiquity of the Cam Deformity: A Comparison of Proximal Femoral Morphology
      Between Early and Modern Humans.
AB  - BACKGROUND: The precise etiology of cam impingement continues to be incompletely
      understood. The prevailing hypothesis posits that the deformity arises as a
      developmental injury prior to skeletal maturation. There is a possible
      evolutionary role, with an aspherical femoral head affording upright humans
      better stability. We set out to identify the antiquity of the cam deformity to
      better understand the comparative roles of modern behavior and evolution in its
      development. METHODS: We used 249 physical specimens of femora from the Libben
      osteological collection, a set of bones from an ancient population who lived
      between the eighth and the eleventh century. These femora were photographed in
      four different orientations, and six specific proximal femoral angles were
      measured. The values were also compared with those from modern human femora using
      the Student t test, with a two-tailed p value of 0.05 denoting significance.
      RESULTS: In total, 249 femora from 175 individuals were included in the final
      analysis. The ages of the individuals ranged between seventeen and fifty-five
      years. Interobserver and intraobserver correlation was good or excellent for all
      variables measured. Compared with modern populations, ancient human hips were
      significantly more anteverted (19.96 degrees  versus 12.85 degrees ; p < 0.001)
      and varus (true neck-shaft angle, 121.96 degrees  versus 129.23 degrees ; p <
      0.001). The alpha angle was significantly lower in ancient humans (35.33 degrees 
      versus 45.61 degrees ; p < 0.001), and none of the ancient femora met the modern
      criteria for a cam deformity (an alpha angle of >50 degrees ). CONCLUSIONS AND
      CLINICAL RELEVANCE: It appears that the cam deformity was nonexistent among
      ancient humans and is perhaps predominantly a product of modern-day stresses.
      Further clinical investigation into behavioral modifications in adolescence is
      warranted to potentially prevent the development of deformity and impingement.

PMID- 26290081
TI  - Preoperative Delayed Gadolinium-Enhanced Magnetic Resonance Imaging of Cartilage
      (dGEMRIC) for Patients Undergoing Hip Arthroscopy: Indices Are Predictive of
      Magnitude of Improvement in Two-Year Patient-Reported Outcomes.
AB  - BACKGROUND: Delayed gadolinium-enhanced magnetic resonance imaging of cartilage
      (dGEMRIC) has been used in the detection of chondropathy. Our study aimed to
      determine whether dGEMRIC indices are predictive of two-year patient-reported
      outcomes and pain scores following hip arthroscopy. METHODS: Between August 2008
      and April 2012, sixty-five patients (seventy-four hips) underwent primary hip
      arthroscopy with preoperative dGEMRIC and a minimum of two years of follow-up.
      Exclusion criteria were previous hip surgery, slipped capital femoral epiphysis,
      inflammatory arthropathy, Legg-Calve-Perthes disease, and arthritis of >1 Tonnis
      grade. Patients were classified in two groups on the basis of a dGEMRIC cutoff of
      323 msec, which was one standard deviation (SD) below the study cohort mean
      dGEMRIC index of 426 msec. Patient-reported outcome tools used included the
      modified Harris hip score (mHHS), the Nonarthritic Hip Score (NAHS), the Hip
      Outcome Score Activities of Daily Living (HOS-ADL), and the Hip Outcome Score
      Sport-Specific Subscale (HOS-SSS) as well as a visual analog scale (VAS) for pain
      and a patient satisfaction score. RESULTS: There were sixty-four hips that met
      the inclusion criteria; fifty-two (81.3%) had a minimum of two years of follow
      up. Twelve of the sixty-four hips had a dGEMRIC index of <323 msec (Group 1), and
      fifty-two hips had a dGEMRIC index of >=323 msec (Group 2). There was no
      significant difference between the groups with respect to age, sex, and body mass
      index. There was no significant difference between the groups in mean
      preoperative patient-reported outcome scores and the VAS for pain. At the two
      year follow-up, Group 1 had significant improvement in the mHHS, whereas Group 2
      demonstrated significant improvement in all patient-reported outcome scores and
      the VAS. The improvement in all patient-reported outcome scores was significantly
      larger for Group 2 compared with Group 1. There was no significant difference in
      patient satisfaction between groups and no significant correlation between
      dGEMRIC indices and the patient-reported outcome measures. CONCLUSIONS: Patients
      with a dGEMRIC index of >=323 msec (less than one SD below the cohort mean)
      demonstrated significantly greater improvement in patient-reported outcome scores
      and the VAS for pain after hip arthroscopy.

PMID- 26290083
TI  - Inpatient Mortality and Morbidity for Dialysis-Dependent Patients Undergoing
      Primary Total Hip or Knee Arthroplasty.
AB  - BACKGROUND: Dialysis-dependent patients can develop osteoarthritis or
      osteonecrosis, warranting hip or knee arthroplasty. Their comorbidities
      predispose them to complications. Our goal was to determine inpatient outcomes of
      dialysis-dependent patients after primary elective total hip or knee
      arthroplasty. METHODS: In the National Inpatient Sample, we identified 2934
      dialysis-dependent patients who had undergone total hip or knee arthroplasty from
      2000 through 2009 and compared them with 6,186,475 patients who had undergone the
      same procedures and were not dialysis-dependent. We described demographic
      characteristics, comorbidities, and outcomes and assessed associations of
      dialysis status with inpatient mortality and complications. RESULTS: In the hip
      arthroplasty group, dialysis-dependent patients were younger (63.2 compared with
      65.2 years; p = 0.0476) and more commonly diagnosed with osteonecrosis (34.29%
      compared with 10.94%; p < 0.0001) than non-dialysis-dependent patients. Dialysis
      dependent patients had higher inpatient mortality rates (1.88% compared with
      0.13%; p < 0.0001) and greater overall complication rates (9.98% compared with
      4.97%; p = 0.0001). Dialysis was an independent risk factor for mortality (odds
      ratio, 6.66; 95% confidence interval [95% CI], 2.66 to 16.66) and complications
      (odds ratio, 1.53; 95% CI, 1.01 to 2.33). In the knee arthroplasty group,
      dialysis-dependent patients were similar in age (66.7 compared with 66.8 years; p
      = 0.8085) and were more commonly diagnosed with osteonecrosis (3.32% compared
      with 0.74%; p < 0.0001) than non-dialysis-dependent patients. Dialysis-dependent
      patients had higher inpatient mortality rates (0.92% compared with 0.10%; p <
      0.0001) and greater overall complication rates (12.48% compared with 5.00%; p <
      0.0001). Dialysis status was an independent risk factor for mortality (odds
      ratio, 3.31; 95% CI, 1.04 to 10.54) and complications (odds ratio, 1.86; 95% CI,
      1.34 to 2.60). CONCLUSIONS: Total hip and knee arthroplasty in dialysis-dependent
      patients presents high risk, with inpatient mortality rates ten to twenty times
      greater and overall complication rates two times greater than in non-dialysis
      dependent patients. Arthroplasty should be approached with caution and preferably
      should be delayed until after renal transplantation.

PMID- 26290082
TI  - Risk Factors for Reoperation in Patients Treated Surgically for Intervertebral
      Disc Herniation: A Subanalysis of Eight-Year SPORT Data.
AB  - BACKGROUND: Lumbar discectomy and laminectomy in patients with intervertebral
      disc herniation (IDH) is common, with variable reported reoperation rates. Our
      study examined which baseline characteristics might be risk factors for
      reoperation and compared outcomes between patients who underwent reoperation and
      those who did not. METHODS: We performed a retrospective subgroup analysis of
      patients from the IDH arm of the Spine Patient Outcomes Research Trial (SPORT)
      randomized and observational cohorts. We analyzed baseline characteristics and
      outcomes of patients who underwent reoperation and those who did not with use of
      data collected from enrollment through eight-years of follow-up after surgery.
      Follow-up times were measured from the time of surgery, and baseline covariates
      were updated to the follow-up immediately preceding the time of surgery for
      outcomes analyses. RESULTS: At eight years, the reoperation rate was 15% (691 no
      reoperation; 119 reoperation). Sixty-two percent of these patients underwent
      reoperation because of a recurrent disc herniation; 25%, because of a
      complication or other factor; and 11%, because of a new condition. The proportion
      of reoperations that were performed for a recurrent disc herniation ranged from
      58% to 62% in the individual years. Older patients were less likely to have
      reoperation (p = 0.015), as were patients presenting with asymmetric motor
      weakness at baseline (p = 0.0003). Smoking, diabetes, obesity, Workers'
      Compensation, and clinical depression were not associated with a greater risk of
      reoperation. Scores on the Short Form (SF)-36 for bodily pain and physical
      functioning, the Oswestry Disability Index (ODI), and the Sciatica Bothersomeness
      Index as well as satisfaction with symptoms had improved less at the time of
      follow-up in the reoperation group (p < 0.001). CONCLUSIONS: In patients who
      underwent surgery for IDH, the overall reoperation rate was 15% at the eight-year
      follow-up. Patients of older age and patients presenting with asymmetric motor
      weakness were less likely to undergo a reoperation. Less improvement in patient
      reported outcomes was noted in the reoperation group.

PMID- 26290084
TI  - Time to Surgery Is Associated with Thirty-Day and Ninety-Day Mortality After
      Proximal Femoral Fracture: A Retrospective Observational Study on Prospectively
      Collected Data from the Danish Fracture Database Collaborators.
AB  - BACKGROUND: We hypothesized that undergoing surgery as soon as possible reduces
      early mortality in patients with a proximal femoral fracture. Our aim was to
      evaluate the association between surgical delay and early mortality in these
      patients. METHODS: We performed a retrospective analysis of prospectively
      collected data from the Danish Fracture Database and the Civil Registration
      System on patients who were fifty years of age or older and had undergone surgery
      for a proximal femoral fracture. Femoral head fracture (classified as OTA/AO 31C
      per the OTA/AO classification system), high-energy trauma, pathological
      fractures, multiple fractures, and surgeries performed with implants not commonly
      used were excluded. End points were adjusted odds ratios for thirty-day and
      ninety-day mortality. RESULTS: For the 3517 surgeries included in this study, the
      median patient age was 82.0 years (range, fifty-one to 107 years), 2458 patients
      (70%) were female, and 1720 surgeries (49%) were performed because of a
      trochanteric fracture. Within twelve hours, 722 of the surgeries (21%) had been
      performed; within twenty-four hours, 2482 surgeries (71%); within thirty-six
      hours, 3024 surgeries (86%); within forty-eight hours, 3242 surgeries (92%); and
      within seventy-two hours, 3353 surgeries (95%). Unsupervised surgeons with an
      education level below that of an attending surgeon performed the surgery in 1807
      (51%) of all cases. The thirty-day mortality was 380 (10.8%) and the ninety-day
      mortality was 612 (17.4%). The risk of thirty-day mortality increased with a
      surgical delay of more than twelve hours (odds ratio, 1.45; p = 0.02), more than
      twenty-four hours (odds ratio, 1.34; p = 0.02), and more than forty-eight hours
      (odds ratio, 1.56; p = 0.02); the risk of ninety-day mortality increased with a
      surgical delay of more than twenty-four hours (odds ratio, 1.23; p = 0.04). An
      education level of the surgeon below that of an attending surgeon increased the
      risk of thirty-day mortality (odds ratio, 1.28; p = 0.035) and ninety-day
      mortality (odds ratio, 1.26; p = 0.016). Increasing American Society of
      Anesthesiologists score and male sex significantly increased both thirty-day and
      ninety-day mortality. CONCLUSIONS: In this study, a surgical delay of more than
      twelve hours significantly increased the adjusted risk of thirty-day mortality
      and a surgical delay of more than twenty-four hours significantly increased the
      adjusted risk of ninety-day mortality. The adjusted risk of both thirty-day and
      ninety-day mortality increased significantly when the education level of the
      surgeon was below that of an attending surgeon. The study findings challenge
      orthopaedic departments to facilitate fast surgical treatment supported by
      attending orthopaedic surgeons.

PMID- 26290085
TI  - Outcomes of Endoscopic Gluteus Medius Repair: Study of Thirty-four Patients with
      Minimum Two-Year Follow-up.
AB  - BACKGROUND: Surgical intervention for partial and full-thickness gluteus medius
      tears is often recommended for patients who have persistent pain despite
      nonoperative treatment. Traditionally, the surgical intervention has been carried
      out through open techniques with good results; however, advantages of endoscopic
      techniques include less tissue dissection, improved tendon mobilization, and the
      benefit of arthroscopic correction of intra-articular pathological conditions.
      The purpose of this report is to provide an update on a previously published
      study of patients with a gluteus medius tear, with inclusion of additional
      patients followed for a minimum of two years. METHODS: The study included thirty
      four patients who had undergone an endoscopic gluteus medius repair with
      correction of intra-articular pathological conditions between April 2009 and
      April 2012 and had been followed for a minimum of two years. Patient-reported
      outcome measures included the modified Harris hip score, Nonarthritic Hip Score,
      and Hip Outcome Score-Activities of Daily Living and Sport-Specific Subscale. A
      visual analog scale (VAS) pain score and a patient satisfaction score were also
      recorded. RESULTS: The cohort consisted of two men and thirty-two women with a
      mean age of fifty-seven years (range, twenty to seventy-nine years). Ten patients
      had a full-thickness tear, and twenty-four patients had a partial-thickness tear.
      Seventeen patients were treated with a suture bridge technique, after completion
      of the tear if it was not already complete, and seventeen patients were treated
      with the transtendinous technique. All patients had surgical correction of intra
      articular pathological conditions. There was a significant improvement in all
      four patient-reported outcomes at three specified time-points. The mean VAS pain
      score decreased from 6.6 preoperatively to 2.4 at the time of the two-year follow
      up (p < 0.001). The mean satisfaction score was 8.5 at two years postoperatively.
      Of twenty-six patients who had a gait deviation preoperatively, fifteen (58%)
      regained a completely normal gait. There was no significant difference in patient
      reported outcome measures between the two surgical techniques. Four patients
      required total hip replacement at eleven to sixteen months postoperatively.
      CONCLUSIONS: After a minimum of two years of follow-up, endoscopic surgical
      repair with correction of intra-articular pathological conditions was found to be
      an effective treatment for patients with a gluteus medius tear.

PMID- 26290086
TI  - An Alumina Ceramic Total Talar Prosthesis for Osteonecrosis of the Talus.
AB  - BACKGROUND: Treatment of osteonecrosis of the talus is challenging. Total talar
      replacement has the potential to restore the function of the ankle joint without
      an associated leg-length discrepancy. The purpose of the present study was to
      investigate postoperative function and pain after total talar replacement in
      patients with osteonecrosis of the talus. METHODS: Fifty-five ankles in fifty-one
      consecutive patients with osteonecrosis of the talus who were treated with a
      total talar replacement from 2005 to 2012 were included in the investigation.
      Scores according to the Japanese Society for Surgery of the Foot (JSSF) ankle
      hindfoot scale and the Ankle Osteoarthritis Scale (AOS) were assessed before
      surgery and at the final follow-up evaluation. RESULTS: According to the JSSF
      ankle-hindfoot scale, the score for pain improved from a mean (and standard
      deviation) of 15 +/- 9.4 points (range, 0 to 20 points) to 34 +/- 5.6 points
      (range, 20 to 40 points); the score for function, from 21.2 +/- 9.7 points
      (range, 4 to 38 points) to 45.1 +/- 4.0 points (range, 37 to 50 points); the
      score for alignment, from 6.0 +/- 2.8 points (range, 5 to 10 points) to 9.8 +/-
      0.9 points (range, 5 to 10 points); and the total score, from 43.1 +/- 17.0
      points (range, 11 to 68 points) to 89.4 +/- 8.4 points (range, 76 to 100 points).
      According to the AOS scale, the score for "pain at its worst" improved from a
      mean of 6.1 +/- 3.3 points (range, 0 to 9.9 points) to 2.0 +/- 1.7 points (range,
      0 to 6.3 points). CONCLUSIONS: Prosthetic talar replacement is a useful procedure
      for patients with osteonecrosis of the talus as it maintains ankle function.

PMID- 26290087
TI  - Treatment of Congenital Vertical Talus: Comparison of Minimally Invasive and
      Extensive Soft-Tissue Release Procedures at Minimum Five-Year Follow-up.
AB  - BACKGROUND: The most common historical treatment method for congenital vertical
      talus is extensive soft-tissue release surgery. A minimally invasive treatment
      approach that relies primarily on serial cast correction was introduced almost
      ten years ago, with promising early results. The purpose of this study was to
      assess the long-term outcome of patients with congenital vertical talus managed
      with the minimally invasive technique and compare them with a cohort treated with
      extensive soft-tissue release surgery. METHODS: The records of twenty-seven
      consecutive patients with vertical talus (forty-two feet) were retrospectively
      reviewed at a mean of seven years (range, five to 11.3 years) after initial
      correction was achieved. The minimally invasive method was used to treat sixteen
      patients (twenty-four feet), and extensive soft-tissue release surgery was used
      to treat eleven patients (eighteen feet). Patient demographics, ankle range of
      motion, the PODCI (Pediatric Outcomes Data Collection Instrument) questionnaire,
      and radiographic measurements were analyzed. RESULTS: At the latest follow-up,
      the mean range of motion of patients treated with the minimally invasive method
      was 42.4 degrees  compared with 12.7 degrees  for patients treated with extensive
      surgery (p < 0.0001). The PODCI normative pain and global function scores were
      superior in the minimally invasive treatment group compared with the extensive
      soft-tissue release group. Greater correction of hindfoot valgus (anteroposterior
      talar axis-first metatarsal base angle) was achieved in the minimally invasive
      treatment group compared with the extensive surgery group (40.1 degrees  versus
      27.9 degrees , p = 0.03), although all other radiographic values were similar
      between the two groups (p > 0.1 for all). Subgroup analysis of patients with
      isolated vertical talus also showed superior range of motion and PODCI normative
      global function scores in the minimally invasive group. CONCLUSIONS: The
      minimally invasive treatment method for vertical talus resulted in better long
      term ankle range of motion and pain scores compared with extensive soft-tissue
      release surgery. Longer-term studies are necessary to determine whether the
      improved outcomes are maintained into adulthood and whether the superior outcome
      is related to reduced scarring.

PMID- 26290088
TI  - Femoral Head Penetration of Vitamin E-Infused Highly Cross-Linked Polyethylene
      Liners: A Randomized Radiostereometric Study of Seventy Hips Followed for Two
      Years.
AB  - BACKGROUND: Highly cross-linked polyethylene infused with vitamin E (E-poly) was
      developed to increase oxidative resistance without affecting mechanical
      properties. We evaluated this type of polyethylene in a randomized clinical study
      that used radiostereometric analysis. Our objective was to compare the early-term
      femoral head penetration of an E-poly liner with that of a heat-treated
      polyethylene liner, ArComXL. We hypothesized that the clinical outcome at two
      years following total hip arthroplasty would be unaffected by the choice of
      polyethylene. METHODS: In this prospective study, sixty-one patients (seventy
      hips) with noninflammatory hip osteoarthritis and a median age of fifty-eight
      years were randomized to receive either an implant with an E-Poly or a heat
      treated highly cross-linked polyethylene liner. The patients were followed for
      two years and evaluated at three time points (three months, one year, and two
      years). RESULTS: The median proximal penetration in the E-poly group increased
      from 0.04 mm at three months to 0.06 mm at two years of follow-up. Corresponding
      values for the ArComXL group were 0.03 mm and 0.10 mm. In both groups,
      significantly increased penetration was observed between three months and two
      years (E-poly, p = 0.02; ArComXL, p < 0.001), but between one and two years, the
      increase was significant only in the control group (E-poly, p = 0.23; ArComXL, p
      = 0.002). CONCLUSIONS: The femoral head penetration of E-poly was very low at two
      years. Whether the increase observed between three months and two years was
      caused by creep, deformation, wear, or a combination of these cannot be
      determined by our study. There were no significant differences observed in
      femoral head penetration rates between E-poly and ArComXL. Currently, the
      theoretical advantages of E-poly remain to be confirmed.

PMID- 26290089
TI  - Supine Position Is Ideal for Manipulation and Pinning of All Types of
      Supracondylar Fractures Compared with the Prone Position.

PMID- 26290090
TI  - A Modified Transtibial Technique Was Similar to an Anteromedial Portal Technique
      for Anterior Cruciate Ligament Reconstruction.

PMID- 26290091
TI  - Treatment with or without an Orthosis is Equivalent for Thoracolumbar Burst
      Fracture without Neurologic Injury.

PMID- 26290092
TI  - What's New in Limb Lengthening and Deformity Correction.

PMID- 26290093
TI  - App Usage Factor: A Simple Metric to Compare the Population Impact of Mobile
      Medical Apps.
AB  - BACKGROUND: One factor when assessing the quality of mobile apps is quantifying
      the impact of a given app on a population. There is currently no metric which can
      be used to compare the population impact of a mobile app across different health
      care disciplines. OBJECTIVE: The objective of this study is to create a novel
      metric to characterize the impact of a mobile app on a population. METHODS: We
      developed the simple novel metric, app usage factor (AUF), defined as the
      logarithm of the product of the number of active users of a mobile app with the
      median number of daily uses of the app. The behavior of this metric was modeled
      using simulated modeling in Python, a general-purpose programming language. Three
      simulations were conducted to explore the temporal and numerical stability of our
      metric and a simulated app ecosystem model using a simulated dataset of 20,000
      apps. RESULTS: Simulations confirmed the metric was stable between predicted
      usage limits and remained stable at extremes of these limits. Analysis of a
      simulated dataset of 20,000 apps calculated an average value for the app usage
      factor of 4.90 (SD 0.78). A temporal simulation showed that the metric remained
      stable over time and suitable limits for its use were identified. CONCLUSIONS: A
      key component when assessing app risk and potential harm is understanding the
      potential population impact of each mobile app. Our metric has many potential
      uses for a wide range of stakeholders in the app ecosystem, including users,
      regulators, developers, and health care professionals. Furthermore, this metric
      forms part of the overall estimate of risk and potential for harm or benefit
      posed by a mobile medical app. We identify the merits and limitations of this
      metric, as well as potential avenues for future validation and research.

PMID- 26290096
TI  - Advance care planning: between tools and relational end-of-life care?

PMID- 26290094
TI  - Micro-anatomical quantitative optical imaging: toward automated assessment of
      breast tissues.
AB  - INTRODUCTION: Pathologists currently diagnose breast lesions through histologic
      assessment, which requires fixation and tissue preparation. The diagnostic
      criteria used to classify breast lesions are qualitative and subjective, and
      inter-observer discordance has been shown to be a significant challenge in the
      diagnosis of selected breast lesions, particularly for borderline proliferative
      lesions. Thus, there is an opportunity to develop tools to rapidly visualize and
      quantitatively interpret breast tissue morphology for a variety of clinical
      applications. METHODS: Toward this end, we acquired images of freshly excised
      breast tissue specimens from a total of 34 patients using confocal fluorescence
      microscopy and proflavine as a topical stain. We developed computerized
      algorithms to segment and quantify nuclear and ductal parameters that
      characterize breast architectural features. A total of 33 parameters were
      evaluated and used as input to develop a decision tree model to classify benign
      and malignant breast tissue. Benign features were classified in tissue specimens
      acquired from 30 patients and malignant features were classified in specimens
      from 22 patients. RESULTS: The decision tree model that achieved the highest
      accuracy for distinguishing between benign and malignant breast features used the
      following parameters: standard deviation of inter-nuclear distance and number of
      duct lumens. The model achieved 81 % sensitivity and 93 % specificity,
      corresponding to an area under the curve of 0.93 and an overall accuracy of 90 %.
      The model classified IDC and DCIS with 92 % and 96 % accuracy, respectively. The
      cross-validated model achieved 75 % sensitivity and 93 % specificity and an
      overall accuracy of 88 %. CONCLUSIONS: These results suggest that proflavine
      staining and confocal fluorescence microscopy combined with image analysis
      strategies to segment morphological features could potentially be used to
      quantitatively diagnose freshly obtained breast tissue at the point of care
      without the need for tissue preparation.

PMID- 26290098
TI  - Rediscovering Holism.

PMID- 26290100
TI  - Reduced sweet and fatty fluid intake after Roux-en-Y gastric bypass in rats is
      dependent on experience without change in stimulus motivational potency.
AB  - Here we assessed how intake reductions induced by Roux-en-Y gastric bypass
      surgery (RYGB) occur within and across access periods by examining drinking
      microstructure. After training, RYGB (n = 8-10) or sham-operated (SHAM, n = 12)
      rats were given 60-min access first to 0.3 M sucrose, then to 5% Intralipid, and
      finally to milk-chocolate Ensure Plus across 5 days each. Initially, total licks
      taken during the first meal of sucrose and Intralipid by RYGB and SHAM rats did
      not differ, but, across subsequent test periods, RYGB rats licked less than SHAM
      rats. First Ensure meal size also did not differ between RYGB and SHAM rats, but
      SHAM rats increased licking across test periods while the behavior of RYGB rats
      remained stable. The intake differences between the surgical groups, when they
      occurred, were most often due to smaller burst sizes in RYGB rats. Importantly,
      the surgical-group difference in sucrose and Intralipid intakes could not be
      explained by altered palatability of these solutions because, throughout testing,
      both groups had similar early meal licking behavior thought to represent the
      motivational potency of stimulus orosensory features. Although, overall, RYGB
      rats displayed lower early meal licking of Ensure relative to the SHAM rats, this
      appeared to be driven primarily by increases in the latter group across test
      periods; the RYGB group stayed relatively stable. Collectively, these results
      suggest that some level of postoral experience with these stimuli and/or their
      components is necessary before intake differences emerge between surgical groups,
      and, even when differences occur, often immediate taste-motivated ingestive
      behavior remains unaltered. 

PMID- 26290102
TI  - An increased population of regulatory T cells improves the pathophysiology of
      placental ischemia in a rat model of preeclampsia.
AB  - The reduced uterine perfusion pressure (RUPP) rat model of preeclampsia exhibits
      much of the pathology characterizing this disease, such as hypertension,
      inflammation, suppressed regulatory T cells (TRegs), reactive oxygen species
      (ROS), and autoantibodies to the ANG II type I receptor (AT1-AA) during
      pregnancy. The objective of this study was to determine whether supplementation
      of normal pregnant (NP) TRegs into RUPP rats would attenuate the pathophysiology
      associated with preeclampsia during pregnancy. CD4(+)/CD25(+) T cells were
      isolated from spleens of NP and RUPP rats, cultured, and injected into gestation
      day (GD) 12 normal pregnant rats that underwent the RUPP procedure on GD 14. On
      GD 1, mean arterial pressure (MAP) was recorded, and blood and tissues were
      collected for analysis. One-way ANOVA was used for statistical analysis. MAP
      increased from 99 +/- 2 mmHg in NP (n = 12) to 127 +/- 2 mmHg in RUPP (n = 21)
      but decreased to 118 +/- 2 mmHg in RUPP+NP TRegs (n = 17). Circulating IL-6 and
      IL-10 were not significantly changed, while circulating TNF-alpha and IL-17 were
      significantly decreased after supplementation of TRegs. Placental and renal ROS
      were 339 +/- 58.7 and 603 +/- 88.1 RLU.min(-1).mg(-1) in RUPP and significantly
      decreased to 178 +/- 27.8 and 171 +/- 55.6 RLU.min(-1).mg(-1), respectively, in
      RUPP+NP TRegs; AT1-AA was 17.81 +/- 1.1 beats per minute (bpm) in RUPP but was
      attenuated to 0.50 +/- 0.3 bpm with NP TRegs. This study demonstrates that NP
      TRegs can significantly improve inflammatory mediators, such as IL-17, TNF-alpha,
      and AT1-AA, which have been shown to increase blood pressure during pregnancy. 

PMID- 26290101
TI  - The roles of sensitization and neuroplasticity in the long-term regulation of
      blood pressure and hypertension.
AB  - After decades of investigation, the causes of essential hypertension remain
      obscure. The contribution of the nervous system has been excluded by some on the
      basis that baroreceptor mechanisms maintain blood pressure only over the short
      term. However, this point of view ignores one of the most powerful contributions
      of the brain in maintaining biological fitness-specifically, the ability to
      promote adaptation of behavioral and physiological responses to cope with new
      challenges and maintain this new capacity through processes involving
      neuroplasticity. We present a body of recent findings demonstrating that prior,
      short-term challenges can induce persistent changes in the central nervous system
      to result in an enhanced blood pressure response to hypertension-eliciting
      stimuli. This sensitized hypertensinogenic state is maintained in the absence of
      the inducing stimuli, and it is accompanied by sustained upregulation of
      components of the brain renin-angiotensin-aldosterone system and other molecular
      changes recognized to be associated with central nervous system neuroplasticity.
      Although the heritability of hypertension is high, it is becoming increasingly
      clear that factors beyond just genes contribute to the etiology of this disease.
      Life experiences and attendant changes in cellular and molecular components in
      the neural network controlling sympathetic tone can enhance the hypertensive
      response to recurrent, sustained, or new stressors. Although the epigenetic
      mechanisms that allow the brain to be reprogrammed in the face of challenges to
      cardiovascular homeostasis can be adaptive, this capacity can also be maladaptive
      under conditions present in different evolutionary eras or ontogenetic periods. 

PMID- 26290103
TI  - Lesser suppression of energy intake by orally ingested whey protein in healthy
      older men compared with young controls.
AB  - Protein-rich supplements are used widely for the management of malnutrition in
      young and older people. Protein is the most satiating of the macronutrients in
      young. It is not known how the effects of oral protein ingestion on energy
      intake, appetite, and gastric emptying are modified by age. The aim of the study
      was to determine the suppression of energy intake by protein compared with
      control and underlying gastric-emptying and appetite responses of oral whey
      protein drinks in eight healthy older men (69-80 yr) compared with eight young
      male controls (18-34 yr). Subjects were studied on three occasions to determine
      the effects of protein loads of 30 g/120 kcal and 70 g/280 kcal compared with a
      flavored water control-drink (0 g whey protein) on energy intake (ad libitum
      buffet-style meal), and gastric emptying (three-dimensional-ultrasonography) and
      appetite (0-180 min) in a randomized, double-blind, cross-over design. Energy
      intake was suppressed by the protein compared with control (P = 0.034).
      Suppression of energy intake by protein was less in older men (1 +/- 5%) than in
      young controls (15 +/- 2%; P = 0.008). Cumulative energy intake (meal+drink) on
      the protein drink days compared with the control day increased more in older (18
      +/- 6%) men than young (1 +/- 3%) controls (P = 0.008). Gastric emptying of all
      three drinks was slower in older men (50% gastric-emptying time: 68 +/- 5 min)
      than young controls (36 +/- 5 min; P = 0.007). Appetite decreased in young, while
      it increased in older (P < 0.05). In summary, despite having slower gastric
      emptying, elderly men exhibited blunted protein-induced suppression of energy
      intake by whey protein compared with young controls, so that in the elderly men,
      protein ingestion increased overall energy intake more than in the young men. 

PMID- 26290104
TI  - Fasting stimulates 2-AG biosynthesis in the small intestine: role of cholinergic
      pathways.
AB  - The endocannabinoids are lipid-derived signaling molecules that control feeding
      and energy balance by activating CB1-type cannabinoid receptors in the brain and
      peripheral tissues. Previous studies have shown that oral exposure to dietary fat
      stimulates endocannabinoid signaling in the rat small intestine, which provides
      positive feedback that drives further food intake and preference for fat-rich
      foods. We now describe an unexpectedly broader role for cholinergic signaling of
      the vagus nerve in the production of the endocannabinoid, 2-arachidonoyl-sn
      glycerol (2-AG), in the small intestine. We show that food deprivation increases
      levels of 2-AG and its lipid precursor, 1,2-diacylglycerol, in rat jejunum mucosa
      in a time-dependent manner. This response is abrogated by surgical resection of
      the vagus nerve or pharmacological blockade of small intestinal subtype-3
      muscarinic acetylcholine (m3 mAch) receptors, but not inhibition of subtype-1
      muscarinic acetylcholine (m1 mAch). We further show that blockade of peripheral
      CB1 receptors or intestinal m3 mAch receptors inhibits refeeding in fasted rats.
      The results suggest that food deprivation stimulates 2-AG-dependent CB1 receptor
      activation through a mechanism that requires efferent vagal activation of m3 mAch
      receptors in the jejunum, which, in turn, may promote feeding after a fast. 

PMID- 26290105
TI  - Intradermal administration of ATP augments methacholine-induced cutaneous
      vasodilation but not sweating in young males and females.
AB  - Acetylcholine released from cholinergic nerves is a key neurotransmitter
      contributing to heat stress-induced cutaneous vasodilation and sweating. Given
      that sympathetic cholinergic nerves also release ATP, ATP may play an important
      role in modulating cholinergic cutaneous vasodilation and sweating. However, the
      pattern of response may differ between males and females given reports of sex
      related differences in the peripheral mechanisms governing these heat loss
      responses. Cutaneous vascular conductance (CVC, laser-Doppler perfusion
      units/mean arterial pressure) and sweat rate (ventilated capsule) were evaluated
      in 17 young adults (8 males, 9 females) at four intradermal microdialysis skin
      sites continuously perfused with: 1) lactated Ringer (Control), 2) 0.3 mM ATP, 3)
      3 mM ATP, or 4) 30 mM ATP. At all skin sites, methacholine was coadministered in
      a concentration-dependent manner (0.0125, 0.25, 5, 100, 2,000 mM, each for 25
      min). In both males and females, CVC was elevated with the lone infusion of 30 mM
      ATP (both P < 0.05), but not with 0.3 and 3 mM ATP compared with control (all P
      >0.27). However, 0.3 mM ATP induced a greater increase in CVC compared with
      control in response to 100 mM methacholine infusion in males (P < 0.05). In
      females, 0.3 mM ATP infusion resulted in a lower concentration of methacholine
      required to elicit a half-maximal response (EC50) (P < 0.05). In both males and
      females, methacholine-induced sweating was unaffected by any concentration of ATP
      (all P > 0.44). We demonstrate that ATP enhances cholinergic cutaneous
      vasodilation albeit the pattern of response differs between males and females.
      Furthermore, we show that ATP does not modulate cholinergic sweating. 

PMID- 26290106
TI  - Peripheral chemoreflex inhibition with low-dose dopamine: new insight into
      mechanisms of extreme apnea.
AB  - The purpose of this study was to determine the impact of peripheral chemoreflex
      inhibition with low-dose dopamine on maximal apnea time, and the related
      hemodynamic and cerebrovascular responses in elite apnea divers. In a randomized
      order, participants performed a maximal apnea while receiving either intravenous
      2 MUg.kg(-1).min(-1) dopamine or volume-matched saline (placebo). The chemoreflex
      and hemodynamic response to dopamine was also assessed during hypoxia [arterial
      O2 tension, (PaO2 ) ~35 mmHg] and mild hypercapnia [arterial CO2 tension (PaCO2 )
      ~46 mmHg] that mimicked the latter parts of apnea. Outcome measures included
      apnea duration, arterial blood gases (radial), heart rate (HR, ECG), mean
      arterial pressure (MAP, intra-arterial), middle (MCAv) and posterior (PCAv)
      cerebral artery blood velocity (transcranial ultrasound), internal carotid (ICA)
      and vertebral (VA) artery blood flow (ultrasound), and the chemoreflex responses.
      Although dopamine depressed the ventilatory response by 27 +/- 41% (vs. placebo;
      P = 0.01), the maximal apnea duration was increased by only 5 +/- 8% (P = 0.02).
      The PaCO2 and PaO2 at apnea breakpoint were similar (P > 0.05). When compared
      with placebo, dopamine increased HR and decreased MAP during both apnea and
      chemoreflex test (P all <0.05). At rest, dopamine compared with placebo dilated
      the ICA (3.0 +/- 4.1%, P = 0.05) and VA (6.6 +/- 5.0%, P < 0.01). During apnea
      and chemoreflex test, conductance of the cerebral vessels (ICA, VA, MCAv, PCAv)
      was increased with dopamine; however, flow (ICA and VA) was similar. At least in
      elite apnea divers, the small increase in apnea time and similar PaO2 at
      breakpoint (~31 mmHg) suggest the apnea breakpoint is more related to PaO2 ,
      rather than peripheral chemoreflex drive to breathe. 

PMID- 26290107
TI  - Point-of-care cardiac troponin test accurately predicts heat stroke severity in
      rats.
AB  - Heat stroke (HS) remains a significant public health concern. Despite the
      substantial threat posed by HS, there is still no field or clinical test of HS
      severity. We suggested previously that circulating cardiac troponin (cTnI) could
      serve as a robust biomarker of HS severity after heating. In the present study,
      we hypothesized that (cTnI) point-of-care test (ctPOC) could be used to predict
      severity and organ damage at the onset of HS. Conscious male Fischer 344 rats (n
      = 16) continuously monitored for heart rate (HR), blood pressure (BP), and core
      temperature (Tc) (radiotelemetry) were heated to maximum Tc (Tc,Max) of 41.9 +/-
      0.1 degrees C and recovered undisturbed for 24 h at an ambient temperature of 20
      degrees C. Blood samples were taken at Tc,Max and 24 h after heat via
      submandibular bleed and analyzed on ctPOC test. POC cTnI band intensity was
      ranked using a simple four-point scale via two blinded observers and compared
      with cTnI levels measured by a clinical blood analyzer. Blood was also analyzed
      for biomarkers of systemic organ damage. HS severity, as previously defined using
      HR, BP, and recovery Tc profile during heat exposure, correlated strongly with
      cTnI (R(2) = 0.69) at Tc,Max. POC cTnI band intensity ranking accurately
      predicted cTnI levels (R(2) = 0.64) and HS severity (R(2) = 0.83). Five markers
      of systemic organ damage also correlated with ctPOC score (albumin, alanine
      aminotransferase, blood urea nitrogen, cholesterol, and total bilirubin; R(2) >
      0.4). This suggests that cTnI POC tests can accurately determine HS severity and
      could serve as simple, portable, cost-effective HS field tests. 

PMID- 26290109
TI  - Body height and arterial pressure in seated and supine young males during +2 G
      centrifugation.
AB  - It is known that arterial pressure correlates positively with body height in
      males, and it has been suggested that this is due to the increasing vertical
      hydrostatic gradient from the heart to the carotid baroreceptors. Therefore, we
      tested the hypothesis that a higher gravito-inertial stress induced by the use of
      a human centrifuge would increase mean arterial pressure (MAP) more in tall than
      in short males in the seated position. In short (162-171 cm; n = 8) and tall (194
      203 cm; n = 10) healthy males (18-41 yr), brachial arterial pressure, heart rate
      (HR), and cardiac output were measured during +2G centrifugation, while they were
      seated upright with the legs kept horizontal (+2Gz). In a separate experiment,
      the same measurements were done with the subjects supine (+2Gx). During +2Gz MAP
      increased in the short (22 +/- 2 mmHg, P < 0.0001) and tall (23 +/- 2 mmHg, P <
      0.0001) males, with no significant difference between the groups. HR increased
      more (P < 0.05) in the tall than in the short group (14 +/- 2 vs. 7 +/- 2 bpm).
      Stroke volume (SV) decreased in the short group (26 +/- 4 ml, P = 0.001) and more
      so in the tall group (39 +/- 5 ml, P < 0.0001; short vs. tall, P = 0.047). During
      +2Gx, systolic arterial pressure increased (P < 0.001) and SV (P = 0.012)
      decreased in the tall group only. In conclusion, during +2Gz, MAP increased in
      both short and tall males, with no difference between the groups. However, in the
      tall group, HR increased more during +2Gz, which could be caused by a larger
      hydrostatic pressure gradient from heart to head, leading to greater inhibition
      of the carotid baroreceptors. 

PMID- 26290108
TI  - PPG neurons of the lower brain stem and their role in brain GLP-1 receptor
      activation.
AB  - Within the brain, glucagon-like peptide-1 (GLP-1) affects central autonomic
      neurons, including those controlling the cardiovascular system, thermogenesis,
      and energy balance. Additionally, GLP-1 influences the mesolimbic reward system
      to modulate the rewarding properties of palatable food. GLP-1 is produced in the
      gut and by hindbrain preproglucagon (PPG) neurons, located mainly in the nucleus
      tractus solitarii (NTS) and medullary intermediate reticular nucleus. Transgenic
      mice expressing glucagon promoter-driven yellow fluorescent protein revealed that
      PPG neurons not only project to central autonomic control regions and mesolimbic
      reward centers, but also strongly innervate spinal autonomic neurons. Therefore,
      these brain stem PPG neurons could directly modulate sympathetic outflow through
      their spinal inputs to sympathetic preganglionic neurons. Electrical recordings
      from PPG neurons in vitro have revealed that they receive synaptic inputs from
      vagal afferents entering via the solitary tract. Vagal afferents convey satiation
      to the brain from signals like postprandial gastric distention or activation of
      peripheral GLP-1 receptors. CCK and leptin, short- and long-term satiety
      peptides, respectively, increased the electrical activity of PPG neurons, while
      ghrelin, an orexigenic peptide, had no effect. These findings indicate that
      satiation is a main driver of PPG neuronal activation. They also show that PPG
      neurons are in a prime position to respond to both immediate and long-term
      indicators of energy and feeding status, enabling regulation of both energy
      balance and general autonomic homeostasis. This review discusses the question of
      whether PPG neurons, rather than gut-derived GLP-1, are providing the
      physiological substrate for the effects elicited by central nervous system GLP-1
      receptor activation. 

PMID- 26290111
TI  - Clinical Risk Factors for the Development of Psoriatic Arthritis Among Patients
      with Psoriasis: A Review of Available Evidence.
AB  - Psoriatic arthritis (PsA), a chronic inflammatory arthritis, affects about 10% of
      patients with psoriasis with higher prevalence seen in patients with more
      extensive skin disease. Early identification of PsA may result in improved
      outcomes. While it remains unclear which patients with psoriasis will develop
      PsA, several studies have identified potential risk factors for PsA among
      patients with psoriasis. This review examines the basic epidemiologic principles
      of identifying risk factors and reviews the evidence to date about risk factors
      for PsA among patients with psoriasis.

PMID- 26290110
TI  - B Cell Therapies, Approved and Emerging: a Review of Infectious Risk and
      Prevention During Use.
AB  - The development of B cell-targeted biologics represents a major advance in the
      treatment of autoimmune rheumatic diseases. As with other immunosuppressive
      agents, risk of infection is a key clinical concern. This review summarises
      safety data from 15 years of experience of rituximab in autoimmune diseases with
      a particular focus on opportunistic infection and class-specific complications
      and infection risk. Rarely, cases of progressive multifocal leucoencephalopathy
      in rituximab-treated patients (5/100 000) have accumulated over time although no
      proven causal association has yet been shown. With repeat cycles of therapy,
      hypogammaglobulinaemia has been observed in a larger proportion of patients and
      is associated with increased risk of serious infections. The infection profile of
      the newer B cell-targeted agent, belimumab, in patients with active systemic
      lupus erythematosus is also discussed. Data from registries are needed to extend
      insights further and also to evaluate for any impact with the difference in mode
      of action of belimumab and infection risk in this population. 

PMID- 26290112
TI  - Myositis Mimics.
AB  - Patients with autoimmune myositis typically present with muscle weakness,
      elevated serum levels of muscle enzymes, and abnormal muscle biopsies. However,
      patients with other acquired myopathies or genetic muscle diseases may have
      remarkably similar presentations. Making the correct diagnosis of another muscle
      disease can prevent these patients from being exposed to the risks of
      immunosuppressive medications, which benefit those with myositis, but not those
      with other types of muscle disease. Here, we review some of the most common
      acquired and inherited muscle diseases that can mimic autoimmune myositis,
      including inclusion body myositis, limb girdle muscular dystrophies, metabolic
      myopathies, mitochondrial myopathies, and endocrine myopathies. We emphasize
      aspects of the medical history, physical exam, laboratory evaluation, and muscle
      biopsy analysis that can help clinicians distinguish myositis mimics from true
      autoimmune myositis. 

PMID- 26290114
TI  - Liquid-assisted tip manipulation: fabrication of twisted bilayer graphene
      superlattices on HOPG.
AB  - We use the tip of a scanning tunneling microscope (STM) to manipulate single
      weakly bound nanometer-sized sheets on a highly oriented pyrolytic graphite
      (HOPG) surface through artificially increasing the tip and sample interaction by
      pretreatment of the surface using a liquid thiol molecule. By this means it is
      possible to tear apart a graphite sheet against a step and fold this part onto
      the HOPG surface and thus generate graphene superlattices with hexagonal
      symmetry. The tip and sample surface interactions, including the van der Waals
      force, electrostatic force and capillary attraction force originating from the
      Laplace pressure due to the formation of a highly curved fluid meniscus
      connecting the tip and sample, are discussed quantitatively to understand the
      formation mechanism of a graphene superlattice induced by the STM tip. The
      capillary force plays a key role in manipulating the graphite surface sheet under
      humid conditions. Our approach provides a simple and feasible route to prepare
      controllable superlattices and graphene nanoribbons and also to better understand
      the process of generation of a graphene superlattice on the surface of HOPG with
      the tip. 

PMID- 26290113
TI  - Less is More: Design of a Highly Stable Disulfide-Deleted Mutant of Analgesic
      Cyclic alpha-Conotoxin Vc1.1.
AB  - Cyclic alpha-conotoxin Vc1.1 (cVc1.1) is an orally active peptide with analgesic
      activity in rat models of neuropathic pain. It has two disulfide bonds, which can
      have three different connectivities, one of which is the native and active form.
      In this study we used computational modeling and nuclear magnetic resonance to
      design a disulfide-deleted mutant of cVc1.1, [C2H,C8F]cVc1.1, which has a larger
      hydrophobic core than cVc1.1 and, potentially, additional surface salt bridge
      interactions. The new variant, hcVc1.1, has similar structure and serum stability
      to cVc1.1 and is highly stable at a wide range of pH and temperatures.
      Remarkably, hcVc1.1 also has similar selectivity to cVc1.1, as it inhibited
      recombinant human alpha9alpha10 nicotinic acetylcholine receptor-mediated
      currents with an IC50 of 13 MUM and rat N-type (Cav2.2) and recombinant human
      Cav2.3 calcium channels via GABAB receptor activation, with an IC50 of ~900 pM.
      Compared to cVc1.1, the potency of hcVc1.1 is reduced three-fold at both
      analgesic targets, whereas previous attempts to replace Vc1.1 disulfide bonds by
      non-reducible dicarba linkages resulted in at least 30-fold decreased activity.
      Because it has only one disulfide bond, hcVc1.1 is not subject to disulfide bond
      shuffling and does not form multiple isomers during peptide synthesis. 

PMID- 26290115
TI  - Herd-scale measurements of methane emissions from cattle grazing extensive sub
      tropical grasslands using the open-path laser technique.
AB  - Methane (CH4) emissions associated with beef production systems in northern
      Australia are yet to be quantified. Methodologies are available to measure
      emissions, but application in extensive grazing environments is challenging. A
      micrometeorological methodology for estimating herd-scale emissions using an
      indirect open-path spectroscopic technique and an atmospheric dispersion model is
      described. The methodology was deployed on five cattle properties across
      Queensland and Northern Territory, with measurements conducted during two
      occasions at one site. On each deployment, data were collected every 10 min for
      up to 7 h a day over 4 to 16 days. To increase the atmospheric concentration of
      CH4 to measurable levels, cattle were confined to a known area around water
      points from ~0800 to 1600 h, during which time measurements of wind statistics
      and line-averaged CH4 concentration were taken. Filtering to remove erroneous
      data accounted for 35% of total observations. For five of the six deployments CH4
      emissions were within the expected range of 0.4 to 0.6 g/kg BW. At one site,
      emissions were ~2 times expected values. There was small but consistent variation
      with time of day, although for some deployments measurements taken early in the
      day tended to be higher than at the other times. There was a weak linear
      relationship (R 2=0.47) between animal BW and CH4 emission per kg BW. Where it
      was possible to compare emissions in the early and late dry season at one site,
      it was speculated that higher emissions at the late dry season may have been
      attributed to poorer diet quality. It is concluded that the micrometeorological
      methodology using open-path lasers can be successfully deployed in extensive
      grazing conditions to directly measure CH4 emissions from cattle at a herd scale.

PMID- 26290116
TI  - Effectiveness of dual-energy computed tomography in providing information on
      pulmonary perfusion and vessel morphology in chronic thromboembolic pulmonary
      hypertension.

PMID- 26290117
TI  - Higher genetic diversity in recolonized areas than in refugia of Alnus glutinosa
      triggered by continent-wide lineage admixture.
AB  - Genetic admixture is supposed to be an important trigger of species expansions
      because it can create the potential for selection of genotypes suitable for new
      climatic conditions. Up until now, however, no continent-wide population genetic
      study has performed a detailed reconstruction of admixture events during natural
      species expansions. To fill this gap, we analysed the postglacial history of
      Alnus glutinosa, a keystone species of European swamp habitats, across its entire
      distribution range using two molecular markers, cpDNA and nuclear
      microsatellites. CpDNA revealed multiple southern refugia located in the Iberian,
      Apennine, Balkan and Anatolian Peninsulas, Corsica and North Africa. Analysis of
      microsatellites variation revealed three main directions of postglacial
      expansion: (i) from the northern part of the Iberian Peninsula to Western and
      Central Europe and subsequently to the British Isles, (ii) from the Apennine
      Peninsula to the Alps and (iii) from the eastern part of the Balkan Peninsula to
      the Carpathians followed by expansion towards the Northern European plains. This
      challenges the classical paradigm that most European populations originated from
      refugial areas in the Carpathians. It has been shown that colonizing lineages
      have met several times and formed secondary contact zones with unexpectedly high
      population genetic diversity in Central Europe and Scandinavia. On the contrary,
      limited genetic admixture in southern refugial areas of A. glutinosa renders rear
      edge populations in the Mediterranean region more vulnerable to extinction due to
      climate change. 

PMID- 26290118
TI  - Pain-associated stressor exposure and neuroendocrine values for premature infants
      in neonatal intensive care.
AB  - Recurrent stress during neonatal intensive care taxes the adaptive capacity of
      the premature infant and may be a risk factor for suboptimal developmental
      outcomes. This research used a descriptive, cross-sectional design and a life
      course perspective to examine the relationship between resting adrenocorticoid
      values at 37 postmenstrual weeks of age and cumulative pain-associated stressor
      exposure in prematurely born infants. Subjects were 59 infants born at under 35
      completed weeks of gestation, who were at least 2 weeks of age, and who had been
      cared for in the NICU since birth. No significant relationships were identified
      between cortisol values and any of the study variables (number of skin breaking
      procedures, hours of assisted ventilation, gestational age at birth, exposure to
      antenatal steroids, history of severe academia, birthweight, days of age to
      attain birthweight, weight at testing, days of age at testing, recent pain
      associated procedures, and 17-OHP value). A significant negative correlation
      (Spearman rank, one-tailed) between the number of skin-breaking procedures and 17
      OHP values was identified (r = -.232, p = .039). Recurrent pain-associated
      stressor exposure may be a more important factor in explaining the variance of 17
      OHP values at 37 postmenstrual weeks of age than birthweight, gestational age, or
      chronological age.

PMID- 26290119
TI  - E-Cigarette use among children and young people: the need for regulation.
AB  - Electronic cigarettes (e-cigarettes) are devices designed to deliver nicotine to
      the body via the route of inhalation. The principle of operation is based on
      heating a nicotine solution in propylene glycol and/or glycerine (e-liquid),
      turning it into aerosol (commonly called 'vapour'), which is then inhaled by the
      user. The scientific evidence on the health consequences of long-term e-cigarette
      use is sparse and currently inconclusive. Young people are the most vulnerable
      group to initiate use of e-cigarettes. The novelty of the e-cigarette,
      perceptions about the harmlessness of the product, a wide variety of flavours
      (fruit, chocolate, peanut butter, bubble gum, gummy bear, amongst others), and
      peer-influence are just a few examples of factors contributing to the e-cigarette
      popularity among youth. The comprehensive e-cigarette regulations need to include
      rules on marketing, safety of newly introduced products (nicotine dosage,
      packaging, and labelling), marketing limitations, and banning the sale of e
      cigarettes to minors. 

PMID- 26290120
TI  - Pulmonary hypertension trials: how can we do better?
AB  - Conducting clinical trials on pulmonary hypertension in the US and Western Europe
      has become increasingly difficult and costly because of many challenges. These
      include a limited patient population that makes recruitment difficult. Recruiting
      internationally has helped, but can add variability. The choice of end points is
      important but ideal end points that reflect pathogenesis of the disease are not
      available. The 6-min walk distance has been used in most trials to date, but
      recent trials have used an 'event-driven' design, in which combined outcomes are
      used to reflect progression of the disease. This design has advantages but
      requires many hundreds of patients and may take up to several years. Thus, there
      is still a role for functional or hemodynamic end points to enable testing of
      more new agents. Assuring the safety and scientific integrity of clinical trials
      without excessive regulation will also help facilitate the evaluation of
      additional therapies for this devastating disease. 

PMID- 26290121
TI  - Is there still a role for high-frequency oscillatory ventilation in neonates,
      children and adults?
AB  - Critically ill patients with respiratory pathology often require mechanical
      ventilation and while low tidal volume ventilation has become the mainstay of
      treatment, achieving adequate gas exchange may not be attainable with
      conventional ventilator modalities. In attempt to achieve gas exchange goals and
      also mitigate lung injury, high frequency ventilation is often implemented which
      couples low tidal volumes with sustained mean airway pressure. This manuscript
      presents the physiology of high-frequency oscillatory ventilation, reviews the
      currently available data on its use and provides strategies and approaches for
      this mode of ventilation. 

PMID- 26290122
TI  - Morphological study of the prostate gland in viscacha (Lagostomus maximus
      maximus) during periods of maximal and minimal reproductive activity.
AB  - The viscacha (Lagostomus maximus maximus) is a rodent with photoperiod-dependent
      seasonal reproduction. The aim of this work was to study the morphological
      variations of the prostate during periods of maximal (summer, long photoperiod)
      and minimal (winter, short photoperiod) reproductive activity. Prostates of adult
      male viscachas were studied by light and electron microscopy,
      immunohistochemistry for androgen receptor, and morphometric analysis. The
      prostate consisted of two regions: peripheral and central. The peripheral zone
      exhibited large adenomeres with a small number of folds and lined with a
      pseudostratified epithelium. The central zone had small adenomeres with
      pseudostratified epithelium and the mucosa showed numerous folds. The morphology
      of both zones showed variations during periods of maximal and minimal
      reproductive activity. The prostate weight, prostate-somatic index, luminal
      diameter of adenomeres, epithelial height and major nuclear diameter decreased
      during the period of minimal reproductive activity. Principal cells showed
      variations in their shape, size and ultrastructural characteristics during the
      period of minimal reproductive activity in comparison with the active period. The
      androgen receptor expression in epithelial and fibromuscular stromal cells was
      different between the studied periods. Our results suggest a reduced secretory
      activity of viscacha prostate during the period of minimal reproductive activity.
      Thus, the morphological variations observed in both the central and peripheral
      zones of the viscacha prostate agree with the results previously obtained in the
      gonads of this rodent of photoperiod-dependent reproduction. Additionally, the
      variations observed in the androgen receptors suggest a direct effect of the
      circulating testosterone on the gland.

PMID- 26290123
TI  - Risk factors for venous thromboembolism in women under combined oral
      contraceptive. The PILl Genetic RIsk Monitoring (PILGRIM) Study.
AB  - Identifying women at risk of venous thromboembolism (VTE) is a major public
      health issue. The objective of this study was to identify environmental and
      genetic determinants of VTE risk in a large sample of women under combined oral
      contraceptives (COC). A total of 968 women who had had one event of VTE during
      COC use were compared to 874 women under COC but with no personal history of VTE.
      Clinical data were collected and a systematic thrombophilia screening was
      performed together with ABO blood group assessment. After adjusting for age,
      family history, and type and duration of COC use, main environmental determinants
      of VTE were smoking (odds ratio [OR] =1.65, 95% confidence interval [1.30-2.10])
      and a body mass index higher than 35 kg.m-2 (OR=3.46 [1.81-7.03]). In addition,
      severe inherited thrombophilia (OR=2.13 [1.32-3.51]) and non-O blood groups
      (OR=1.98 [1.57-2.49]) were strong genetic risk factors for VTE. Family history
      poorly predicted thrombophilia as its prevalence was similar in patients with or
      without first degree family history of VTE (29.3% vs 23.9%, p=0.09). In
      conclusion, this study confirms the influence of smoking and obesity and shows
      for the first time the impact of ABO blood group on the risk of VTE in women
      under COC. It also confirms the inaccuracy of the family history of VTE to detect
      inherited thrombophilia.

PMID- 26290124
TI  - Letter to the Editor.

PMID- 26290125
TI  - Lymphocytes reduce nigrostriatal deficits in the 6-hydroxydopamine mouse model of
      Parkinson's disease.
AB  - Neuroinflammation is a well-known neuropathological feature of Parkinson's
      disease (PD), but it remains controversial whether it is causal or consequential
      to neurodegeneration. While the role of microglia in the pathogenesis has been
      thoroughly investigated in human and different rodent models, data concerning the
      impact of the adaptive immune system on the pathogenesis of PD are still rare,
      although lymphocyte populations were found in brain tissue of PD patients and
      have been implicated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      mediated neurodegeneration in mice. To test the hypothesis that the adaptive
      immune system contributes to the progression of PD in the murine 6
      hydroxydopamine (6-OHDA) model, we performed unilateral 6-OHDA injection into the
      medial forebrain bundle and compared wild-type mice with recombination activating
      gene-1 deficient mice (RAG-1(-/-)), that lack mature lymphocytes. After 6-OHDA
      injection, immune-deficient mice moved significantly slower and less often than
      wild-type mice. Rotarod analysis displayed a shorter latency to fall in RAG-1(-/
      ) mice. Immunohistochemical analysis in wild-type mice demonstrated a higher CD8+
      T cell density in the ipsilesional striatum compared to sham-operated animals.
      Cell counts of tyrosine hydroxylase positive dopaminergic neurons of the
      substantia nigra in immune compromised mice were significantly reduced compared
      to wild-type mice. Wild type bone marrow reconstitution into RAG-1(-/-)
      recipients rescued the clinical deterioration as well as the neurodegeneration in
      RAG-1(-/-) deficient recipients ameliorated clinical symptoms and
      neurodegeneration after 6-OHDA treatment. Our data indicate that lymphocytes
      reduce the clinical and neuropathological impact of 6-OHDA lesioning and thus may
      play a protective role in this toxic mouse model of PD.

PMID- 26290126
TI  - How are different neural networks related to consciousness?
AB  - OBJECTIVE: We aimed to investigate the roles of different resting-state networks
      in predicting both the actual level of consciousness and its recovery in brain
      injury patients. METHODS: We investigated resting-state functional connectivity
      within different networks in patients with varying levels of consciousness:
      unresponsive wakefulness syndrome (UWS; n = 56), minimally conscious state (MCS;
      n = 29), and patients with brain lesions but full consciousness (BL; n = 48).
      Considering the actual level of consciousness, we compared the strength of
      network connectivity among the patient groups. We then checked the presence of
      connections between specific regions in individual patients and calculated the
      frequency of this in the different patient groups. Considering the recovery of
      consciousness, we split the UWS group into 2 subgroups according to recovery:
      those who emerged from UWS (UWS-E) and those who remained in UWS (UWS-R). The
      above analyses were repeated on these 2 subgroups. RESULTS: Functional
      connectivity strength in salience network (SN), especially connectivity between
      the supragenual anterior cingulate cortex (SACC) and left anterior insula (LAI),
      was reduced in the unconscious state (UWS) compared to the conscious state (MCS
      and BL). Moreover, at the individual level, SACC-LAI connectivity was more
      present in MCS than in UWS. Default-mode network (DMN) connectivity strength,
      especially between the posterior cingulate cortex (PCC) and left lateral parietal
      cortex (LLPC), was reduced in UWS-R compared with UWS-E. Furthermore, PCC-LLPC
      connectivity was more present in UWS-E than in UWS-R. INTERPRETATION: Our
      findings show that SN (SACC-LAI) connectivity correlates with behavioral signs of
      consciousness, whereas DMN (PCC-LLPC) connectivity instead predicts recovery of
      consciousness.

PMID- 26290127
TI  - Calciphylaxis with evidence of hypercoagulability successfully treated with
      unfractionated heparin: a multidisciplinary approach.
AB  - Calciphylaxis is characterized by abnormal calcification of vessels and skin;
      however, its aetiology and pathogenesis remain unclear. Entities frequently
      associated with calciphylaxis are end-stage renal disease, diabetes mellitus,
      hypercalcaemia, hyperphosphataemia, elevated calcium-phosphate product,
      hyperparathyroidism and possible hypercoagulable states. Skin lesions may remain
      quiescent or may develop suddenly and progress rapidly. They are more common on
      the legs. Treatment of calciphylaxis is very challenging and requires
      interdisciplinary management. We present a case that highlights the difficulty of
      treating calciphylaxis. A multidisciplinary approach was vital for the proper
      treatment of our patient. This case also demonstrates the importance of searching
      for underlying hypercoagulable states, especially in recalcitrant cases. In cases
      of calciphylaxis with vessel occlusion from microthrombi, heparin therapy would
      be a logical next step. The effect of anticoagulation may be rapid and
      impressive. 

PMID- 26290128
TI  - Evaluation of two commercial PRRSV antibody ELISA kits with samples of known
      status and singleton reactors.
AB  - Two commercial PRRSV ELISA kits (IDEXX and Bionote) were evaluated for their
      sensitivity and specificity using 476 PRRS-positive serum samples collected from
      7 animal challenge experiments and 1,000 PRRS-negative sera. Both ELISA kits
      exhibited 100% sensitivity with sera collected 14 to 42 days post-infection, and
      the results from the kits were highly correlated (R(2)=0.9207). The specificity
      of IDEXX or Bionote kit was 99.9% or 99.7%, respectively. In addition, the
      Bionote ELISA kit was used to examine 100 sera that were determined to be falsely
      positive either by IDEXX 2XR or 3XR ELISA, and only 7 of these samples were found
      to be positive. These results indicate that both ELISA kits exhibited similar
      levels of sensitivity and specificity and would complement one another for the
      verification of false-positive samples. 

PMID- 26290129
TI  - Effects of inactive parapoxvirus ovis on cytokine levels in rats.
AB  - The aim of this study is to determine the effects of iPPOV on pro-inflammatory
      and anti-inflammatory cytokine levels in rats. iPPOV (1 ml/rat) was administered
      intraperitoneal route to 49 rats, except for 7 rats (Control, 0 group). Serum
      samples were collected from 7 rats at 1st, 2nd, 4th, 8th, 12th, 16th and 24th hr
      after treatments. Levels of TNF-alpha, IL-6, IL-12 and IL-10 were determined
      using ELISA. Administration of iPPOV stimulated TNF-alpha (16th and 24th hr) and
      IL-6 (12th, 16th and 24th hr) synthesis and caused fluctuations in IL-10 and IL
      12 concentrations. In conclusion, increased cytokine levels could be attributed
      to immunomodulatory activity of iPPOV, however, detailed studies are required to
      fully understand effects of iPPOV on immune system. 

PMID- 26290130
TI  - Protective efficacy of stockpiled vaccine against H5N8 highly pathogenic avian
      influenza virus isolated from a chicken in Kumamoto prefecture, Japan, in 2014.
AB  - H5 highly pathogenic avian influenza (HPAI) viruses have spread worldwide, and
      antigenic variants of different clades have been selected. In this study, the
      national stockpiled vaccine prepared from A/duck/Hokkaido/Vac-1/2004 (H5N1)
      strain was evaluated for the protective efficacy against H5N8 HPAI virus isolated
      in Kumamoto prefecture, Japan, in April 2014. In the challenge test, all of the
      vaccinated chickens survived without showing any clinical signs and reduced virus
      shedding. It was concluded that the present stockpiled vaccine was effective
      against the H5N8 HPAI virus. 

PMID- 26290131
TI  - X-linked intellectual disability related genes disrupted by balanced X-autosome
      translocations.
AB  - Detailed molecular characterization of chromosomal rearrangements involving X
      chromosome has been a key strategy in identifying X-linked intellectual
      disability-causing genes. We fine-mapped the breakpoints in four women with
      balanced X-autosome translocations and variable phenotypes, in order to
      investigate the corresponding genetic contribution to intellectual disability. We
      addressed the impact of the gene interruptions in transcription and discussed the
      consequences of their functional impairment in neurodevelopment. Three patients
      presented with cognitive impairment, reinforcing the association between the
      disrupted genes (TSPAN7-MRX58, KIAA2022-MRX98, and IL1RAPL1-MRX21/34) and
      intellectual disability. While gene expression analysis showed absence of TSPAN7
      and KIAA2022 expression in the patients, the unexpected expression of IL1RAPL1
      suggested a fusion transcript ZNF611-IL1RAPL1 under the control of the ZNF611
      promoter, gene disrupted at the autosomal breakpoint. The X-chromosomal
      breakpoint definition in the fourth patient, a woman with normal intellectual
      abilities, revealed disruption of the ZDHHC15 gene (MRX91). The expression assays
      did not detect ZDHHC15 gene expression in the patient, thus questioning its
      involvement in intellectual disability. Revealing the disruption of an X-linked
      intellectual disability-related gene in patients with balanced X-autosome
      translocation is a useful tool for a better characterization of critical genes in
      neurodevelopment. (c) 2015 Wiley Periodicals, Inc. 

PMID- 26290132
TI  - Ecological and evolutionary impacts of changing climatic variability.
AB  - While average temperature is likely to increase in most locations on Earth, many
      places will simultaneously experience higher variability in temperature,
      precipitation, and other climate variables. Although ecologists and evolutionary
      biologists widely recognize the potential impacts of changes in average climatic
      conditions, relatively little attention has been paid to the potential impacts of
      changes in climatic variability and extremes. We review the evidence on the
      impacts of increased climatic variability and extremes on physiological,
      ecological and evolutionary processes at multiple levels of biological
      organization, from individuals to populations and communities. Our review
      indicates that climatic variability can have profound influences on biological
      processes at multiple scales of organization. Responses to increased climatic
      variability and extremes are likely to be complex and cannot always be
      generalized, although our conceptual and methodological toolboxes allow us to
      make informed predictions about the likely consequences of such climatic changes.
      We conclude that climatic variability represents an important component of
      climate that deserves further attention.

PMID- 26290133
TI  - Post-pandemic influenza A (H1N1) 2009 virus infection in pregnant women in Ceara,
      Brazil.
AB  - OBJECTIVE: The aim of this study was to present results of the post-pandemic
      phase of A(H1N1)pdm09 virus infection in pregnant women in Ceara, Brazil, during
      the January-June 2012 influenza season. RESULTS: One hundred and fifty-four
      nasopharyngeal swab samples were collected from pregnant women admitted to
      hospitals with suspected severe acute respiratory infection (SARI). Fifty-three
      (34.4%) had laboratory-confirmed A(H1N1)pdm09 virus infection with 15 (28.3%)
      outpatients and 38 (71.7%) hospitalized. Five (9.4%) women were in the first
      trimester of pregnancy, 20 (37.7%) in the second trimester of pregnancy, and 24
      (45.2%) in the third trimester of pregnancy. Three had no information about the
      time of pregnancy. Six samples from newborns were also analyzed, of which three
      were nasopharyngeal swab positive for A(H1N1)pdm09. These swabs were collected
      immediately after birth, with the exception of one that was collected on the day
      after birth. CONCLUSION: Our findings suggest that transplacental transfer of
      influenza viruses could occur as a result of severe illness in pregnancy. It is
      therefore important to encourage women to be vaccinated against influenza in
      order to avoid pregnancy complications.

PMID- 26290134
TI  - Temperament and Personality in Bariatric Surgery-Resisting Temptations?
AB  - Temperament and personality traits can serve as both risk factors as well as
      protective factors in the development of morbid obesity. In the present review,
      we present an overview of studies focusing on the relationship between
      temperament/personality and morbid obesity in pre-operative and postoperative
      bariatric surgery patients. We consider studies that focus on both a categorical
      and dimensional point of view on temperament/personality, as well as studies
      based on cross-sectional and longitudinal designs. Finally, we will integrate the
      research findings, discuss the implications for assessment and treatment and
      formulate suggestions for future research.

PMID- 26290135
TI  - Spectral-domain optical coherence tomography of macula in myopia.
AB  - The aim of this study is to determine the associations between regional macular
      thickness and gender, age, axial length, and degree of myopia in young and middle
      aged healthy myopic eyes. One hundred and seventy-one subjects with -0.5 diopters
      of myopia or worse underwent prospective macular thickness measurement by
      Spectralis spectral-domain optical coherence tomography. Subjects' mean age was
      32.40 +/- 8.25 years (range 18 to 49 years), with 45 % being male. The mean
      degree of myopia was -4.57 +/- 3.52 diopters, with a mean axial length of 25.09
      +/- 1.67 mm. Multivariate regression analysis demonstrated significantly thicker
      central (mean 9.13 um thicker) and inner subfields (mean 8.55 um thicker) in
      males (P values were <0.001 and 0.002, respectively). In addition, in both
      genders, for each millimeter of increased axial length, the central subfield
      thickness increased by 2.11 um, the inner subfield decreased by 2.25 um, and the
      outer subfield decreased by 3.62 um (P values were 0.010, <0.001, and <0.001,
      respectively). Factors including gender and axial length affect baseline regional
      macular thickness in young and middle-age myopic subjects. The central subfield
      and inner subfield were affected by both gender and axial length, while the outer
      subfield was affected only by axial length. The macular thickness of myopic
      subjects with macular disease should be interpreted in light of these factors. 

PMID- 26290137
TI  - Mental health problems in Kosovar adolescents: results from a national mental
      health survey.
AB  - PURPOSE: Our purpose was to determine the effects of gender and age on Kosovar
      YSR scores and the prevalence of self-reported behavioral/emotional problems in
      Kosovar adolescents based on scores above a cutpoint. METHODS: Participants were
      1351 adolescents recruited from secondary schools in seven regions of Kosova who
      completed the Youth Self-Report. RESULTS: The oldest adolescents had the highest
      scores on many YSR scales. Although Kosova's mean problems scores were not
      elevated relative to international norms, the percentage of adolescents scoring
      in the deviant range (borderline + clinical) was much higher than expected for
      almost all YSR problem scales, including Total Problems (31.2%), Internalizing
      (40.8%), and Externalizing (23.4%). The 23% prevalence of elevated scores on
      Stress Problems was triple the expected 7% prevalence based on a 93rd percentile
      cutpoint. CONCLUSION: Results revealed much higher prevalence of psychopathology
      than would be expected based on international norms, with 25-40% of Kosovar
      adolescents scoring in the deviant range on YSR scales, Thus, our research
      indicates a need for expanding psychiatry services to meet the pressing mental
      health needs of Kosovar adolescents as well as the importance of considering
      mental health problems in their social context.

PMID- 26290138
TI  - Evolutionarily distant pathogens require the Arabidopsis phytosulfokine
      signalling pathway to establish disease.
AB  - Secreted peptides and their specific receptors frequently orchestrate cell-to
      cell communication in plants. Phytosulfokines (PSKs) are secreted tyrosine
      sulphated peptide hormones, which trigger cellular dedifferentiation and
      redifferentiation upon binding to their membrane receptor. Biotrophic plant
      pathogens frequently trigger the differentiation of host cells into specialized
      feeding structures, which are essential for successful infection. We found that
      oomycete and nematode infections were characterized by the tissue-specific
      transcriptional regulation of genes encoding Arabidopsis PSKs and the PSK
      receptor 1 (PSKR1). Subcellular analysis of PSKR1 distribution showed that the
      plasma membrane-bound receptor internalizes after binding of PSK-alpha.
      Arabidopsis pskr1 knockout mutants were impaired in their susceptibility to downy
      mildew infection. Impaired disease susceptibility depends on functional salicylic
      acid (SA) signalling, but not on the massive up-regulation of SA-associated
      defence-related genes. Knockout pskr1 mutants also displayed a major impairment
      of root-knot nematode reproduction. In the absence of functional PSKR1, giant
      cells arrested their development and failed to fully differentiate. Our findings
      indicate that the observed restriction of PSK signalling to cells surrounding
      giant cells contributes to the isotropic growth and maturation of nematode
      feeding sites. Taken together, our data suggest that PSK signalling in
      Arabidopsis promotes the differentiation of host cells into specialized feeding
      cells.

PMID- 26290139
TI  - In vitro and in vivo characterization of the anticancer activity of Thai
      stingless bee (Tetragonula laeviceps) cerumen.
AB  - Tetragonula laeviceps cerumen was sequentially extracted with 80% (v/v) methanol,
      dichloromethane, and hexane and also in the reverse order. By the MTT assay and
      the respective 50% inhibition concentration value, the most active fraction was
      further purified to apparent homogeneity by bioassay-guided silica gel column
      chromatography. alpha-Mangostin was identified by high-resolution electrospray
      ionization mass spectrometry and nuclear magnetic resonance analyses. It had a
      potent cytotoxicity against the BT474, Chago, Hep-G2, KATO-III, and SW620 cell
      lines (IC50 values of 1.22 +/- 0.03, 2.25 +/- 0.20, 0.94 +/- 0.01, 0.88 +/- 0.16,
      and 1.50 +/- 0.39 umol/L, respectively). The in vitro cytotoxicity of alpha
      mangostin against the five human cancer cell lines and primary fibroblasts was
      further characterized by real-time impedance-based analysis. Interestingly, alpha
      mangostin was more cytotoxic against the cancer-derived cell lines than against
      the primary fibroblasts. Later, the migration assay was performed by continuously
      measuring the attachment of cells to the plate electrodes at the bottom of the
      transwell membrane. The combined caspase-3 and -7 activities were assayed by the
      Caspase-Glo(r) 3/7 kit. It showed that the cytotoxic mechanism involved caspase
      independent apoptosis, while at low (non-toxic) concentrations alpha-mangostin
      did not significantly alter cell migration. Furthermore, the in vivo cytotoxicity
      and angiogenesis were determined by alkaline phosphatase staining in zebrafish
      embryos along with monitoring changes in the transcript expression level of two
      genes involved in angiogenesis (vegfaa and vegfr2) by quantitative real-time
      reverse transcriptase- polymerase chain reaction. It was found that the in vivo
      cytotoxicity of alpha-mangostin against zebrafish embryos had a 50% lethal
      concentration of 9.4 uM, but no anti-angiogenic properties were observed in
      zebrafish embryos at 9 and 12 uM even though it downregulated the expression of
      vegfaa and vegfr2 transcripts. Thus, alpha-mangostin is a major active compound
      with a potential anticancer activity in T. laeviceps cerumen in Thailand. 

PMID- 26290140
TI  - The gastroprotective effect of pogostone from Pogostemonis Herba against
      indomethacin-induced gastric ulcer in rats.
AB  - Pogostemonis Herba, known as "Guang-Huo-Xiang" in Chinese, has been widely used
      in the treatment of gastrointestinal dysfunction. Pogostone is one of the major
      constituents of Pogostemonis Herba. The aim was to scientifically evaluate the
      possible gastroprotective effect and the underlying mechanisms of pogostone
      against indomethacin-induced gastric ulcer in rats. Rats were orally treated with
      vehicle, lansoprazole (30 mg/kg) or pogostone (10, 20 and 40 mg/kg) and
      subsequently exposed to acute gastric lesions induced by indomethacin. Gross
      evaluation, histological observation, gastric mucosal superoxide dismutase
      activity, glutathione content, catalase activity, malonaldehyde level and
      prostaglandin E2 production were performed. Immunohistochemistry and reverse
      transcription polymerase chain reaction for cyclooxygenase-1 and cyclooxygenase
      2, as well as terminal deoxynucleotidyltransferase-mediated dUTP nick-end
      labeling assay, immunohistochemistry for heat-shock protein 70, B-cell lymphoma-2
      and Bax were conducted. Results indicated that rats pretreated with pogostone
      showed remarkable protection from the gastric mucosa damage compared to vehicle
      treated rats based on the ulcer index and inhibition percentage. Histologically,
      oral administration of pogostone resulted in observable improvement of gastric
      injury, characterized by reduction of necrotic lesion, flattening of gastric
      mucosa and alleviation of submucosal edema with hemorrhage. Pogostone
      pretreatment significantly raised the depressed activities of superoxide
      dismutase, glutathione and catalase, while reduced the elevated malonaldehyde
      level compared with indomethacin-induced group. Pogostone-pretreated group
      induced a significant increase in gastric mucosal prostaglandin E2 level and
      obvious up-regulation of protein levels and mRNA expressions of cyclooxygenase-1
      and cyclooxygenase-2. Furthermore, antiapoptotic effect of pogostone was verified
      by terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling assay,
      and the apoptotic process triggered by pogostone involved the up-expression of
      heat-shock protein70 and B-cell lymphoma-2 protein, and suppression of Bax
      protein expressions in the ulcerated tissues. It is speculated that the
      gastroprotective effect of pogostone against indomethacin-induced gastric
      ulceration might be associated with its stimulation of cyclooxygenase-mediated
      prostaglandin E2, antioxidant and antiapoptotic effect. 

PMID- 26290141
TI  - Inflation with carbon monoxide in rat donor lung during cold ischemia phase
      ameliorates graft injury.
AB  - Carbon monoxide (CO) attenuates lung ischemia reperfusion injury (IRI) via
      inhalation, and as an additive dissolved in flush/preservation solution. This
      study observed the effects of lung inflation with CO on lung graft function in
      the setting of cold ischemia. Donor lungs were inflated with 40% oxygen + 60%
      nitrogen (control group) or with 500 ppm CO + 40% oxygen + nitrogen (CO group)
      during the cold ischemia phase and were kept at 4C for 180 min. Recipients were
      sacrificed by exsanguinations at 180 min after reperfusion. Rats in the sham
      group had no transplantation and were performed as the recipients. Compared with
      the sham group, the oxygenation determined by blood gas analysis and the pressure
      volume curves of the lung grafts decreased significantly, while the wet
      weight/dry weight (W/D) ratio, inflammatory reaction, oxidative stress, and cell
      apoptosis increased markedly (P < 0.05). However, compared to the control group,
      CO treatment improved the oxygenation (381 +/- 58 vs. 308 +/- 78 mm Hg) and the
      pressure-volume curves (15.8 +/- 2.4 vs. 11.6 +/- 1.7 mL/kg) (P < 0.05). The W/D
      ratio (4.6 +/- 0.6) and the serum levels of interleukin-8 (279 +/- 46 pg/mL) and
      tumor necrosis factor-alpha (377 +/- 59 pg/mL) in the CO group decreased
      significantly compared to the control group (5.8 +/- 0.8, 456 +/- 63 pg/mL, and
      520 +/- 91 pg/mL) (P < 0.05). In addition, CO inflation also significantly
      decreased malondialdehyde activity and apoptotic cells in grafts, and increased
      the superoxide dismutase content. Briefly, CO inflation in donor lungs in the
      setting of cold ischemia attenuated lung IRI and improved the graft function
      compared with oxygen. 

PMID- 26290142
TI  - The impact of posterior vitreous adhesion on ischaemia in eyes with retinal vein
      occlusion.
AB  - PURPOSE: To evaluate whether posterior vitreous adhesion (PVA) contributes to
      retinal ischaemia in eyes suffering from central (CRVO) or branch retinal vein
      occlusion (BRVO). METHODS: Retrospective patient chart analysis of eyes with
      CRVO/BRVO receiving pars-plana vitrectomy (ppV). Prior to surgery fluorescence
      angiography was conducted to classify RVO as ischaemic or not. RESULTS: Sixty
      eyes were included, thereof 36 (60%)/24 (40%) with CRVO/BRVO. In the CRVO group,
      17 (47%)/19 (53%) eyes were classified as ischaemic/non-ischaemic. Respective
      results for BRVO-affected eyes were 16 (67%)/8 (33%). PVA/posterior vitreous
      detachment (PVD) was found in 33 (92%)/3 (8%) eyes with CRVO and in 23 (96%)/1
      (4%) patients suffering from BRVO. Value differences of PVA/PVD between ischaemic
      and non-ischaemic-typed RVO failed statistical significance for both, CRVO (p =
      0.095) and BRVO (p = 1.0). CONCLUSIONS: Posterior vitreous adhesion had no impact
      on retinal ischaemia in this investigation. As an attached posterior vitreous
      cortex acts as a scaffold and thus significantly increases neovascularization
      (NV) development in ischaemic-typed RVO, a prospective study evaluating the
      effect of enzymatic vitreolysis is indicated.

PMID- 26290143
TI  - A novel nanoparticle containing neuritin peptide with grp170 induces a CTL
      response to inhibit tumor growth.
AB  - Malignant glioma is among the most challenging of all cancers to treat
      successfully. Despite recent advances in surgery, radiotherapy and chemotherapy,
      current treatment regimens have only a marginal impact on patient survival. In
      this study, we constructed a novel nanoparticle containing neuritin peptide with
      grp170. The nanoparticle could elicit a neuritin-specific cytotoxic T lymphocyte
      response to lyse glioma cells in vitro. In addition, the nanoparticle could
      inhibit tumor growth and improve the lifespan of tumor-bearing mice in vivo.
      Taken together, the results demonstrated that the nanoparticle can inhibit tumor
      growth and represents a promising therapy for glioma. 

PMID- 26290145
TI  - Distribution of mutations in DNMT3A gene and the suitability of mutations in R882
      codon for MRD monitoring in patients with AML.
AB  - The DNA methyl-transferase 3A gene (DNMT3A) is the third most frequently mutated
      gene in cytogenetically normal acute myeloid leukemia (CN-AML) patients (20-30
      %), who belong to a group of patients with intermediate risk. About 60 % of
      mutations in this gene have been identified in the arginine codon R882. To date,
      there is no consensus on whether these mutations can be used as biomarkers for
      monitoring of minimal residual disease and management of preemptive AML therapy.
      We studied the occurrence of mutations in the DNMT3A gene in our cohort of
      patients and their persistence during AML treatment. Using next-generation
      sequencing, we identified four mutations in 11/25 of our analyzed patients-
      frequent R882C and R882H mutations, rare Y735S mutation, and a novel L347P
      mutation. Mutation R882C was detected in 5/11, R882H in 4/11 patients, and Y735S
      and L347P in one patient each. In 4/7 patients initially carrying mutations in
      the R882 codon, we found the persistence of mutations also during complete
      remission with, however, no correlation to AML kinetics. Our findings suggest
      that mutations in the DNMT3A gene can only be used as a biomarker for those AML
      patients in whom DNMT3A mutation is lost after therapy.

PMID- 26290144
TI  - CCND2, CTNNB1, DDX3X, GLI2, SMARCA4, MYC, MYCN, PTCH1, TP53, and MLL2 gene
      variants and risk of childhood medulloblastoma.
AB  - Recent studies have described a number of genes that are frequently altered in
      medulloblastoma tumors and that have putative key roles in the development of the
      disease. We hypothesized that common germline genetic variations in these genes
      may be associated with medulloblastoma development. Based on recent publications,
      we selected 10 genes that were frequently altered in medulloblastoma: CCND2,
      CTNNB1, DDX3X, GLI2, SMARCA4, MYC, MYCN, PTCH1, TP53, and MLL2 (now renamed as
      KMT2D). Common genetic variants (single nucleotide polymorphisms) annotating
      these genes (n = 221) were genotyped in germline DNA (neonatal dried blood spot
      samples) from 243 childhood medulloblastoma cases and 247 control subjects from
      Sweden and Denmark. Eight genetic variants annotating three genes in the sonic
      hedgehog signaling pathway; CCND2, PTCH1, and GLI2, were found to be associated
      with the risk of medulloblastoma (P(combined) < 0.05). The findings were however
      not statistically significant following correction for multiple testing by the
      very stringent Bonferroni method. The results do not support our hypothesis that
      common germline genetic variants in the ten studied genes are associated with the
      risk of developing medulloblastoma.

PMID- 26290146
TI  - Reply to the Letter to the Editor.

PMID- 26290148
TI  - Evaluation of macular choroidal thickness using spectral-domain optical coherence
      tomography in patients with obstructive sleep apnoea syndrome: comment.

PMID- 26290147
TI  - Characterization of the Genital Microenvironment of Female Rhesus Macaques Prior
      to and After SIV Infection.
AB  - PROBLEM: HIV infection among women is frequently modeled in female rhesus
      macaques. Longitudinal studies on genital compartment and hormonal factors that
      can influence susceptibility to SIV infection are lacking in this animal model.
      METHOD OF STUDY: Genital specimens and menstruation of indoor-housed female
      rhesus macaques were analyzed prior to and after SIV infection. RESULTS: Median
      menstrual cycle length averaged 27 days, although highly variable cycle lengths
      and frequent periods of amenorrhea were observed during summer months. The
      vaginal microbiota, characterized by adapted Nugent scoring, showed predominance
      of small Gram-variable rods and Gram-positive cocci. Highly variable vaginal
      cytokine levels were observed pre- and post-SIV infection. Vaginal viral loads
      correlated with plasma viral loads, but were not associated with progesterone
      levels. CONCLUSION: These results provide an integrated characterization of
      important factors in the vaginal microenvironment that are relevant to the
      experimental design of HIV prevention and transmission studies in female rhesus
      macaques.

PMID- 26290149
TI  - Associations of human leukocyte antigens with autoimmune diseases: challenges in
      identifying the mechanism.
AB  - The mechanism of genetic associations between human leukocyte antigen (HLA) and
      susceptibility to autoimmune disorders has remained elusive for most of the
      diseases, including rheumatoid arthritis (RA) and type 1 diabetes (T1D), for
      which both the genetic associations and pathogenic mechanisms have been
      extensively analyzed. In this review, we summarize what are currently known about
      the mechanisms of HLA associations with RA and T1D, and elucidate the potential
      mechanistic basis of the HLA-autoimmunity associations. In RA, the established
      association between the shared epitope (SE) and RA risk has been explained, at
      least in part, by the involvement of SE in the presentation of citrullinated
      peptides, as confirmed by the structural analysis of DR4-citrullinated peptide
      complex. Self-peptide(s) that might explain the predispositions of variants at
      11beta and 13beta in DRB1 to RA risk have not currently been identified.
      Regarding the mechanism of T1D, pancreatic self-peptides that are presented
      weakly on the susceptible HLA allele products are recognized by self-reactive T
      cells. Other studies have revealed that DQ proteins encoded by the T1D
      susceptible DQ haplotypes are intrinsically unstable. These findings indicate
      that the T1D susceptible DQ haplotypes might confer risk for T1D by facilitating
      the formation of unstable HLA-self-peptide complex. The studies of RA and T1D
      reveal the two distinct mechanistic basis that might operate in the HLA
      autoimmunity associations. Combination of these mechanisms, together with other
      functional variations among the DR and DQ alleles, may generate the complex
      patterns of DR-DQ haplotype associations with autoimmunity. 

PMID- 26290151
TI  - Detection of viable myocardium and scar tissue.

PMID- 26290152
TI  - Characterization and inhibition studies of carbonic anhydrase from gill of
      Russian Sturgeon Fish (Acipenser gueldenstaedtii).
AB  - An alpha-carbonic anhydrase (CA, EC 4.2.1.1) was purified and characterized
      kinetically from gill of Acipenser gueldenstaedtii as an endangered sturgeon
      species. The carbonic anhydrase was purified 66-folds with yield 20.7% by
      Sepharose-4B-l-tyrosine-sulfanilamide affinity column and the specific activity
      was determined as 222.2 EU/mg protein. Km and Vmax kinetic values for gill
      carbonic anhydrase were calculated by a Lineweaver-Burk graph using p-nitrophenol
      acetate (p-NPA) as a substrate, and was defined as 2.5 mM and 5 * 10(6 )MUM/min,
      respectively. It was observed that CA from the sturgeon gill in the presence of
      the sulfanilamide and acetazolamide as an inhibitor had very low IC50 values such
      as 13.0 and 0.1 MUM, respectively. In addition, it was determined that the enzyme
      was inhibited by Fe(2+,) Co(2+,) Ni(2+), and Zn(2+)-Ba(2+) with the IC50 values
      of 0.2, 1.7, 1.2, and 1.1 mM, respectively. 

PMID- 26290150
TI  - The genomic landscape of human immune-mediated diseases.
AB  - As the methodology of genetic detection has developed rapidly in recent years,
      through techniques such as genome-wide association studies (GWAS) and the
      secondary generation of sequencing, we are able to view the genomic landscape
      more clearly. It is well known that genes have a vital role in the pathogenesis
      of immune-mediated diseases (IMDs), which could provide important insight into
      new clinical therapeutic targets. Here, we review the genomic landscape of IMDs
      and analyse overlapping loci between diseases. There may be a need for more
      epigenetics studies to aid in the understanding of the transition from genotype
      to phenotype. 

PMID- 26290153
TI  - Chirped pulse Raman amplification in warm plasma: towards controlling saturation.
AB  - Stimulated Raman backscattering in plasma is potentially an efficient method of
      amplifying laser pulses to reach exawatt powers because plasma is fully broken
      down and withstands extremely high electric fields. Plasma also has unique
      nonlinear optical properties that allow simultaneous compression of optical
      pulses to ultra-short durations. However, current measured efficiencies are
      limited to several percent. Here we investigate Raman amplification of short
      duration seed pulses with different chirp rates using a chirped pump pulse in a
      preformed plasma waveguide. We identify electron trapping and wavebreaking as the
      main saturation mechanisms, which lead to spectral broadening and gain saturation
      when the seed reaches several millijoules for durations of 10's - 100's fs for
      250 ps, 800 nm chirped pump pulses. We show that this prevents access to the
      nonlinear regime and limits the efficiency, and interpret the experimental
      results using slowly-varying-amplitude, current-averaged particle-in-cell
      simulations. We also propose methods for achieving higher efficiencies. 

PMID- 26290154
TI  - Function does not follow form in gene regulatory circuits.
AB  - Gene regulatory circuits are to the cell what arithmetic logic units are to the
      chip: fundamental components of information processing that map an input onto an
      output. Gene regulatory circuits come in many different forms, distinct
      structural configurations that determine who regulates whom. Studies that have
      focused on the gene expression patterns (functions) of circuits with a given
      structure (form) have examined just a few structures or gene expression patterns.
      Here, we use a computational model to exhaustively characterize the gene
      expression patterns of nearly 17 million three-gene circuits in order to
      systematically explore the relationship between circuit form and function. Three
      main conclusions emerge. First, function does not follow form. A circuit of any
      one structure can have between twelve and nearly thirty thousand distinct gene
      expression patterns. Second, and conversely, form does not follow function. Most
      gene expression patterns can be realized by more than one circuit structure. And
      third, multifunctionality severely constrains circuit form. The number of circuit
      structures able to drive multiple gene expression patterns decreases rapidly with
      the number of these patterns. These results indicate that it is generally not
      possible to infer circuit function from circuit form, or vice versa. 

PMID- 26290155
TI  - What role can the rural pipeline play in the recruitment and retention of rural
      allied health professionals?
AB  - CONTEXT: People living in rural areas have poorer health than their urban
      counterparts with higher morbidity and mortality rates and lower life expectancy.
      Challenges attracting health professionals to work in rural locations in
      Australia and elsewhere have been well- documented. In response, the idea of a
      rural pipeline emerged in the medical literature as a career pathway for doctors,
      conceptualised as a career continuum starting at school and ending in a
      committed, appropriately trained and supported rural doctor. This article draws
      on the literature to consider how the concept of a rural pipeline can be used to
      enhance recruitment and retention of allied health professionals (AHPs) in
      Australia. The complexity of the issue is taken into account, acknowledging the
      diverse professional, organisational and social needs within and between AHPs and
      their different career pathways. With this in mind, the rural pipeline is adapted
      and extended to focus on AHPs who enter at any stage of their career to work in
      rural areas. ISSUES: Barriers to recruitment and retention require multifaceted
      strategies to encourage and support AHPs at various stages along the pipeline to
      enter, and remain in, rural practice. Findings from the literature identify
      discrete themes within and between AHPs about factors influencing their rural
      recruitment and retention choices and include career stage at entry to rural
      practice, age, gender, social context, professional support, organisational
      environment and public-private practice mix in service delivery. These findings
      underscored the development of an extended rural pipeline adapted to specifically
      target AHPs. This flexible framework of entry to rural practice can be applied at
      any stage of their career and includes suggestions of strategies to support
      retention. LESSONS LEARNED: Evidence from studies of rural AHPs suggests a
      flexible approach to recruitment and retention is needed that takes into account
      the complexity of the issue. The extended rural pipeline adapted to AHPs avoids a
      one-size-fits-all approach. Instead, it offers a more nuanced approach that
      addresses the diversity within and between professions and reflects the different
      stages at which AHPs enter rural practice that can inform recruitment and
      retention strategies that better meet their needs.

PMID- 26290156
TI  - The Restorative Role of Apology in Resolving Medical Disputes: Lessons From
      Chinese Legal Culture.
AB  - This article is the first exploration of the Chinese notion of apology from a
      comparative legal perspective. By reviewing the significance of apology in the
      context of Chinese culture, the article presents a three-dimensional structure of
      apology that, in contrast to the understanding the research community now has,
      defines acknowledgement of fault, admission of responsibility, and offer of
      reparation as three essential elements of an apology. It is the combination of
      these three elements that enables apology to serve as a form of reparation. The
      article further places the three-dimensional apology in the context of the
      Chinese concept of "the relations of humanity," arguing that an apology
      accompanying admission of fault and responsibility may help to restore the
      harmony of relations and, by so doing, resolve medical disputes positively. 

PMID- 26290157
TI  - Systematic review with meta-analysis: the risk of gastrointestinal haemorrhage
      post-polypectomy in patients receiving anti-platelet, anti-coagulant and/or
      thienopyridine medications.
AB  - BACKGROUND: For patients undergoing colonoscopy with polypectomy, current
      guidelines recommend temporary cessation of blood-thinning medications. The data
      regarding periprocedural management of these medications are sparse. AIM: To
      perform a systematic review and meta-analysis to determine the risk of post
      polypectomy bleeding (PPB) in patients taking anti-platelet, anti-coagulant
      and/or thienopyridine medications. METHODS: We searched Pubmed, Scopus, Web of
      Science, Biosis and Proceedings First from 1970 to 2015. PPB was defined as overt
      haemorrhage or drop in haemoglobin of at least 2 g/dL. RESULTS: Of 1490 articles
      identified, we included 3 papers and 1 abstract with patients on aspirin and/or
      NSAIDs, 1 paper on warfarin, 2 abstracts on clopidogrel, and 2 papers on
      clopidogrel plus aspirin and/or NSAIDs. While the rate of immediate PPB on
      aspirin and/or NSAIDs was not increased (OR = 1.1, 95% CI 0.7-1.9, P = 0.7), the
      risk of delayed PPB was increased (OR = 1.7, 95% CI 1.0-2.4, P = 0.0009, I(2)  =
      60%) but rendered non-significant with elimination of a small study. There was an
      elevated risk of delayed PPB on clopidogrel (OR = 9.7, 95% CI 3.1-30.8, P = 0.0,
      I(2)  = 0). There was an increased risk of delayed PPB in patients on clopidogrel
      + aspirin and/or NSAIDs (OR = 3.4, 95% CI 1.3-8.8, P = 0.01, I(2)  = 0). Based on
      a single study on warfarin, the PPB rate was elevated. There were no data
      regarding PPB and usage of the newer anti-coagulant agents. CONCLUSIONS: Usage of
      aspirin or NSAIDs does not increase risk of post-polypectomy bleeding.
      Clopidogrel and warfarin should be discontinued in the periprocedural period to
      prevent the occurrence of post-polypectomy bleeding.

PMID- 26290158
TI  - Inhibition of nonhomologous end joining to increase the specificity of
      CRISPR/Cas9 genome editing.
AB  - DNA repair, one of the fundamental processes occurring in a cell, safeguards the
      genome and maintains its integrity. Among various DNA lesions, double-strand
      breaks are considered to be the most deleterious, as they can lead to potential
      loss of genetic information, if not repaired. Nonhomologous end joining (NHEJ)
      and homologous recombination are two major double-strand break repair pathways.
      SCR7, a DNA ligase IV inhibitor, was recently identified and characterized as a
      potential anticancer compound. Interestingly, SCR7 was shown to have several
      applications, owing to its unique property as an NHEJ inhibitor. Here, we focus
      on three main areas of research in which SCR7 is actively being used, and discuss
      one of the applications, i.e. genome editing via CRISPR/Cas, in detail. In the
      past year, different studies have shown that SCR7 significantly increases the
      efficiency of precise genome editing by inhibiting NHEJ, and favouring the error
      free homologous recombination pathway, both in vitro and in vivo. Overall, we
      discuss the current applications of SCR7 to shed light on the unique property of
      the small molecule of having distinct applications in normal and cancer cells,
      when used at different cellular concentrations.

PMID- 26290159
TI  - Probabilistic cardiac and respiratory based classification of sleep and apneic
      events in subjects with sleep apnea.
AB  - Current clinical standards to assess sleep and its disorders lack either accuracy
      or user-friendliness. They are therefore difficult to use in cost-effective
      population-wide screening or long-term objective follow-up after diagnosis. In
      order to fill this gap, the use of cardiac and respiratory information was
      evaluated for discrimination between different sleep stages, and for detection of
      apneic breathing. Alternative probabilistic visual representations were also
      presented, referred to as the hypnocorrogram and apneacorrogram. Analysis was
      performed on the UCD sleep apnea database, available on Physionet. The presence
      of apneic events proved to have a significant impact on the performance of a
      cardiac and respiratory based algorithm for sleep stage classification. WAKE
      versus SLEEP discrimination resulted in a kappa value of kappa = 0.0439, while
      REM versus NREM resulted in kappa = 0.298 and light sleep (N1N2) versus deep
      sleep (N3) in kappa = 0.339. The high proportion of hypopneic events led to poor
      detection of apneic breathing, resulting in a kappa value of kappa = 0.272. While
      the probabilistic representations allow to put classifier output in perspective,
      further improvements would be necessary to make the classifier reliable for use
      on patients with sleep apnea.

PMID- 26290160
TI  - Establishment of the biochemical and endocrine blood profiles in the Majorera and
      Palmera dairy goat breeds: the effect of feed restriction.
AB  - Feed restriction, and seasonal weight loss (SWL), are major setbacks for animal
      production in the tropics and the Mediterranean. They may be solved through the
      use of autochthonous breeds particularly well adapted to SWL. It is therefore of
      major importance to determine markers of tolerance to feed restriction of
      putative use in animal selection. Two indigenous breeds from the Canary Islands,
      Palmera and Majorera, are commonly used by dairy goat farmers and, interestingly,
      have different phenotype characteristics albeit with a common ancestry. Indeed,
      Majorera is well adapted to feed restriction whereas the Palmera is susceptible
      to feed restriction. In addition, regardless of their importance in dairy
      production, there are only a limited number of reports relating to these breeds
      and, to the best of our knowledge, there is no description of their blood
      metabolite standard values under control conditions or as affected by feed
      restriction. In this study we analysed the blood metabolite profiles in Majorera
      and Palmera goats aiming to establish the differential responses to feed
      restriction between the two breeds and to characterise their metabolite standard
      values under control conditions. We observed significant differences in
      creatinine, urea, non-esterified fatty acids (NEFAs), cholesterol, IGF-1 and T3
      due to underfeeding. Furthermore, a PCA analysis, revealed that animals submitted
      to undernutrition could be distinguished from the control groups, with the
      formation of three separate clusters (Palmera individuals after 22 d of
      subnutrition (PE22); Majorera individuals after 22 d of subnutrition (ME22) and
      animals assigned to control conditions (MC0, MC22, PC0 and PC22)), highlighting
      different responses of the two breeds to undernutrition. 

PMID- 26290161
TI  - Chimerism analysis in clinical practice and its relevance for the detection of
      graft rejection and malignant relapse in pediatric hematopoietic stem cell
      transplant patients.
AB  - Chimerism and clinical outcome data from 244 hematopoietic stem cell transplants
      in 218 children were retrospectively analyzed to assess their relevance for the
      detection of graft rejection and malignant relapse. Patients transplanted for a
      non-malignant disease had significantly higher proportions of residual recipient
      T cells in peripheral blood at one, three, and six months compared with patients
      transplanted for malignant disease. Recipient T-cell levels were below 50% at one
      month after transplantation in most patients (129 of 152 transplants). Graft
      rejection occurred more frequently in the group of patients with high levels of
      recipient cells at one month (10 graft rejections in the 23 patients with
      recipient T cells >50% at one month as compared to seven graft rejections
      occurred in 129 patients with recipient T cells <50% (p < 0.001). Multilineage
      chimerism data in 87 children with leukemia at one, three, and six months after
      transplantation were not correlated with subsequent relapse of malignant disease.
      In conclusion, early analysis of lineage-specific chimerism in peripheral blood
      can be used to identify patients who are at high risk of graft rejection.
      However, the efficacy of early chimerism analysis for predicting leukemia relapse
      was limited.

PMID- 26290162
TI  - Novel insight for midline cyst formation in prostate: The involvement of
      decreased prenatal testosterone suggested by second-to-fourth digit ratio study.
AB  - OBJECTIVES: To clarify the relationship between midline cyst formation and second
      to fourth finger length ratio. METHODS: The present study included 95 benign
      prostatic hyperplasia patients and 61 healthy male college students. All midline
      cysts were identified by transrectal ultrasonography. In the benign prostatic
      hyperplasia group, 45 midline cyst (+) men (M(age) = 67.2 years) and age-matched
      50 midline cyst (-) men (M(age) = 67.1 years) were included. In the university
      student group, 12 midline cyst (+) men (M(age) = 21.7 years) and age-matched 49
      midline cyst (-) men (Mage = 21.1 years) were included. We took photocopies of
      the participants' bilateral hands, and measured the second and fourth finger
      length was measured by one examiner in a blind manner. RESULTS: Second to fourth
      finger length ratios in the benign prostatic hyperplasia group (right/left mean
      +/- SD) were higher bilaterally in midline cyst (+) (0.95 +/- 0.03/0.95 +/- 0.03)
      than those in midline cyst (-) (0.92 +/- 0.03/0.92 +/- 0.03; P < 0.0001/P =
      0.0010). Second to fourth finger length ratios in students were higher only in
      the right hand in midline cyst (+) (0.96 +/- 0.03/0.94 +/- 0.03) than those in
      midline cyst (-) (0.93 +/- 0.03/0.94 +/- 0.03; P = 0.0018/P = 0.9968). The second
      to fourth finger length ratio of midline cyst (+) men was significantly higher
      than that in midline cyst (-) men. CONCLUSIONS: The second to fourth finger
      length ratio is higher in subjects with midline cyst of the prostate. It can be
      speculated that the prostatic utricle dilates in cases less exposed to male
      hormones during fetal development.

PMID- 26290163
TI  - A case of systemic lupus erythematosus following polyalkylimide dermal filler.

PMID- 26290164
TI  - Professional bodies should provide accreditation of healthcare services to
      improve patient safety.

PMID- 26290165
TI  - Religious discrimination and common mental disorders in England: a nationally
      representative population-based study.
AB  - PURPOSE: Although the impact of discrimination on mental health has been
      increasingly discussed, the effect of religious discrimination has not been
      examined systematically. We studied the prevalence of perceived religious
      discrimination and its association with common mental disorders in a nationally
      representative population-based sample in England. METHODS: We used data from the
      Adult Psychiatric Morbidity Survey 2007 that represents all adults age 16 years
      and over living in private households in England. Common mental disorders were
      ascertained using the Revised Clinical Interview Schedule. Experience of
      discrimination was assessed by a computer-assisted self-report questionnaire and
      potential paranoid traits by the Psychosis Screening Questionnaire. RESULTS: From
      the total of 7318 participants, 3873 (52.4%) reported adhering to religion. 108
      subjects (1.5%) reported being unfairly treated in the past 12 months due to
      their religion. Non-Christian religious groups were more likely to report
      perceived religious discrimination compared to Christians (OR 11.44; 95% CI 7.36
      17.79). People who experienced religious discrimination had increased prevalence
      of all common mental disorders. There was a two-fold increase in the risk of
      common mental disorders among people who reported experience of religious
      discrimination independent of their ethnicity, skin colour or suspected paranoid
      traits. CONCLUSIONS: The impact of perceived religious discrimination on mental
      health should be given more consideration in treatment and future preventative
      policies.

PMID- 26290167
TI  - Efficacy of Neurofeedback Versus Pharmacological Support in Subjects with ADHD.
AB  - Behavioral training in neurofeedback has proven to be an essential complement to
      generalize the effects of pharmacological support in subjects who have attention
      deficit with hyperactivity disorder (ADHD). Therefore, this investigation
      attempts to analyze the efficacy of neurofeedback compared with pharmacological
      support and the combination of both. Participants were 131 students, classified
      into four groups: control (did not receive neurofeedback or pharmacological
      support), neurofeedback group, pharmacological support group, and combined group
      (neurofeedback + pharmacological support). Participants' executive control and
      cortical activation were assessed before and after treatment. Results indicate
      that the combined group obtained more benefits and that the neurofeedback group
      improved to a greater extent in executive control than the pharmacological
      support group. It is concluded that this kind of training may be an alternative
      to stimulate activation in subjects with ADHD.

PMID- 26290166
TI  - Correlation of NLRP3 with severity and prognosis of coronary atherosclerosis in
      acute coronary syndrome patients.
AB  - We decided to assess the prognostic value of NLRP3 inflammasome level in acute
      coronary syndrome (ACS) patients and whether it was related to coronary
      atherosclerotic severity. Study population included one-hundred and twenty-three
      (123) subjects. Peripheral blood monocyte NLRP3 protein level was correlated with
      clinical presentation, angiographic characteristics and its scoring systems as
      well as GRACE and TIMI risk scores. Follow-up for major adverse cardiac events
      (MACE) was carried out at 180 days. Peripheral blood monocyte NLRP3 was found to
      be elevated in ACS patients (P < 0.05) and showed positive correlation with GRACE
      score (r = 0.619), TIMI score (r = 0.580), SYNTAX score (r = 0.550), Clinical
      SYNTAX score (r = 0.564) and Gensini score (r = 0.516). NLRP3 was also increased
      with increasing number of vessels, the number of lesions present and the presence
      bifurcation lesions (P < 0.05). Multivariate Cox regression analysis showed NLRP3
      to be an independent predictor of MACE (P = 0.043). Kaplan-Meier analysis and
      receiver operating characteristic curves for NLRP3 showed good predictive value
      for MACE. There is a positive correlation of NLRP3 level with severity of
      coronary atherosclerosis. NLRP3 level is a promising prognostic utility and is
      efficient in event prediction for MACE. 

PMID- 26290168
TI  - A first look at the influence of anthropogenic climate change on the future
      delivery of fluvial sediment to the Ganges-Brahmaputra-Meghna delta.
AB  - We employ a climate-driven hydrological water balance and sediment transport
      model (HydroTrend) to simulate future climate-driven sediment loads flowing into
      the Ganges-Brahmaputra-Meghna (GBM) mega-delta. The model was parameterised using
      high-quality topographic data and forced with daily temperature and precipitation
      data obtained from downscaled Regional Climate Model (RCM) simulations for the
      period 1971-2100. Three perturbed RCM model runs were selected to quantify the
      potential range of future climate conditions associated with the SRES A1B
      scenario. Fluvial sediment delivery rates to the GBM delta associated with these
      climate data sets are projected to increase under the influence of anthropogenic
      climate change, albeit with the magnitude of the increase varying across the two
      catchments. Of the two study basins, the Brahmaputra's fluvial sediment load is
      predicted to be more sensitive to future climate change. Specifically, by the
      middle part of the 21(st) century, our model results suggest that sediment loads
      increase (relative to the 1981-2000 baseline period) over a range of between 16%
      and 18% (depending on climate model run) for the Ganges, but by between 25% and
      28% for the Brahmaputra. The simulated increase in sediment flux emanating from
      the two catchments further increases towards the end of the 21(st) century,
      reaching between 34% and 37% for the Ganges and between 52% and 60% for the
      Brahmaputra by the 2090s. The variability in these changes across the three
      climate change simulations is small compared to the changes, suggesting they
      represent a significant increase. The new data obtained in this study offer the
      first estimate of whether and how anthropogenic climate change may affect the
      delivery of fluvial sediment to the GBM delta, informing assessments of the
      future sustainability and resilience of one of the world's most vulnerable mega
      deltas. Specifically, such significant increases in future sediment loads could
      increase the resilience of the delta to sea-level rise by giving greater
      potential for vertical accretion. However, these increased sediment fluxes may
      not be realised due to uncertainties in the monsoon related response to climate
      change or other human-induced changes in the catchment: this is a subject for
      further research. 

PMID- 26290169
TI  - Finding the keys to successful adult-targeted advertisements on obesity
      prevention: an experimental audience testing study.
AB  - BACKGROUND: Mass media communications are an important component of comprehensive
      interventions to address population levels of overweight and obesity, yet we have
      little understanding of the effective characteristics of specific advertisements
      (ads) on this topic. This study aimed to quantitatively test audience reactions
      to existing adult-focused public health television ads addressing overweight and
      obesity to determine which ads have the highest levels of message acceptance,
      argument strength, personalised perceived effectiveness and negative emotional
      impact. METHODS: 1116 Australian adults aged 21-55 years recruited from a
      national online panel participated in this web-based study. Quotas were applied
      to achieve even numbers of males and females, those aged 21-29 years and 30-55
      years, and those with a healthy weight (BMI = 18.5-24.9) and overweight/obesity
      (BMI = 25+). Participants were randomly assigned to view and rate four of eight
      ads that varied in terms of message content (health consequences,
      supportive/encouraging or social norms/acceptability) and execution style
      (graphic, simulation/animation, positive or negative testimonial, or depicted
      scene). RESULTS: Toxic fat (a graphic, health consequences ad) was the top
      performing ad on all four outcome measures and was significantly more likely than
      the other ads tested to promote strong responses in terms of message acceptance,
      argument strength and negative emotional impact. Measure up (a negative
      testimonial, health consequences ad) performed comparably on personalised
      perceived effectiveness. Most ads produced stronger perceptions of personalised
      perceived effectiveness among participants with overweight/obesity compared to
      participants with healthy weight. Some ads were more likely to promote strong
      negative emotions among participants with overweight/obesity. CONCLUSIONS:
      Findings provide preliminary evidence of the most promising content and
      executional styles of ads that could be pursued as part of obesity prevention
      campaigns. Ads emphasising the negative health consequences of excess weight
      appear to elicit stronger cognitive and emotional responses from adults with
      overweight/obesity. However, careful pre-testing of these types of ads is needed
      prior to their inclusion in actual campaigns to ensure they do not have
      unintended negative impacts such as increased stigmatisation of vulnerable
      individuals and increased levels of body dissatisfaction and/or eating-disordered
      behaviour among at-risk population sub-groups.

PMID- 26290170
TI  - Effects of coordinate-system construction methods on postoperative computed
      tomography evaluation of implant orientation after total hip arthroplasty.
AB  - OBJECTIVE: In total hip arthroplasty, it is important to assess postoperative
      implant orientation. The computed tomography-based (CT-based) three-dimensional
      (3D) templating method using 3D preoperative planning software is generally
      recommended. In this method, postoperative implant orientation within a bony
      coordinate system can be measured by overlaying a 3D computerized model of the
      implant on a real postoperative CT image of the implant. The bony coordinate
      system consists of several reference points (RPs) marked on a CT image of the
      bone surface. Therefore, preoperative and postoperative coordinate systems do not
      always match. We investigated how the difference between coordinate systems
      constructed from RPs chosen by manual methods (M1 and M2) and those constructed
      by the computer matching method influences the results of measurement validation.
      METHODS: In M1, postoperative RPs were chosen without a specific tool in a single
      planning module. In M2, postoperative RPs were chosen with as little deviation as
      possible from preoperative RPs, verifying preoperative RPs on another monitor.
      RESULTS: M1 and M2 produced mean errors in acetabular cup inclination of 0.7
      degrees  +/- 0.5 degrees  and 0.5 degrees  +/- 0.3 degrees , respectively, and
      mean errors in cup anteversion of 1.3 degrees  +/- 1.2 degrees  and 0.5 degrees 
      +/- 0.4 degrees , respectively, which were statistically significant differences.
      M1 and M2 produced mean errors in femoral stem anteversion of 2.4 degrees  +/-
      2.0 degrees  and 2.7 degrees  +/- 2.1 degrees , respectively, not a significant
      difference, but these errors were larger than errors in cup orientation.
      DISCUSSION: We recommend referring to preoperative RPs when choosing
      postoperative RPs. Surgeons must be aware that for evaluation of postoperative
      stem anteversion, manual methods may produce considerable error.

PMID- 26290171
TI  - A mild and regioselective route to functionalized quinazolines.
AB  - A Rh-catalyzed ortho-amidation cyclocondensation sequence gave a range of 4
      aminoquinazolines in high yield. The method features a remarkably mild C(sp(2)
      )?H activation step and can be exploited to rapidly access compounds with
      established biological activity. 

PMID- 26290172
TI  - Indicators based on registers and administrative data for breast cancer: routine
      evaluation of oncologic care pathway can be implemented.
AB  - RATIONALE, AIMS AND OBJECTIVES: Assuring the best standards of care - in a
      sustainable way - in chronic diseases as breast cancer is nowadays an important
      challenge for any health system. The aim of this study was to present the
      methodology used to define a set of quality indicators, computable from
      administrative data for the pathway of care of breast cancer, and its application
      at a population level. METHOD: The cohort of 2007-2009 incident cases of breast
      cancer was identified through a network of six cancer registers in Northern
      Italy. Cases of sarcoma and lymphoma, patients with multiple primary cancers and
      those metastatic at diagnosis were excluded; 9614 women were retained for the
      analysis. For each indicator, the sub-cohort of women eligible for the
      diagnostic/therapeutic procedures was identified and calculations were performed
      through record linkage between the cohort and sources of health information. Data
      on potential available confounders or prognostic factors were also collected.
      RESULTS: For a few indicators, such as cyto-histological assessment before
      surgery (62%) and intensive follow-up (79%), deviation from recommendations was
      evident. Younger patients (<=50 years) more frequently needed a short term re
      intervention, while older patients less frequently underwent reconstructive
      surgery and received palliative care. Several indicators had a great variability
      across hospitals. In some cases, this heterogeneity appeared to be related to the
      hospital size, with high-volume hospitals being more compliant to guidelines.
      CONCLUSION: It is possible to evaluate the quality of cancer care delivered in
      clinical practice in recent years, in order to implement interventions aimed to
      improve adherence to international standards of care.

PMID- 26290173
TI  - Integration of carbohydrate metabolism and redox state controls dauer larva
      formation in Caenorhabditis elegans.
AB  - Under adverse conditions, Caenorhabditis elegans enters a diapause stage called
      the dauer larva. External cues signal the nuclear hormone receptor DAF-12, the
      activity of which is regulated by its ligands: dafachronic acids (DAs). DAs are
      synthesized from cholesterol, with the last synthesis step requiring NADPH, and
      their absence stimulates dauer formation. Here we show that NADPH levels
      determine dauer formation in a regulatory mechanism involving key carbohydrate
      and redox metabolic enzymes. Elevated trehalose biosynthesis diverts glucose-6
      phosphate from the pentose phosphate pathway, which is the major source of
      cellular NADPH. This enhances dauer formation due to the decrease in the DA
      level. Moreover, DAF-12, in cooperation with DAF-16/FoxO, induces negative
      feedback of DA synthesis via activation of the trehalose-producing enzymes TPS
      1/2 and inhibition of the NADPH-producing enzyme IDH-1. Thus, the dauer
      developmental decision is controlled by integration of the metabolic flux of
      carbohydrates and cellular redox potential. 

PMID- 26290175
TI  - Saturated amine oxides: part 10. hydroacridines: part 32. linear 17O/13C and
      13C/13C chemical shift correlations between saturated azaheterocyclic N
      methylamine N-oxides, and the methiodides of their parent amines.
AB  - Two kinds of good linear correlations were found between the chemical shifts of
      saturated six-membered azaheterocyclic N-methylamine N-oxides and the chemical
      shifts of the methiodides of their parent amines. One of the correlations occurs
      between the (17)O chemical shift of the N(+)-O(-) oxygen in the N-oxides and the
      (13)C chemical shift of the N(+)-CH3 methyl group analogously situated in the
      appropriate methiodide (r = 0.9778). This correlation enables unambiguous
      configuration assignment of the N(+)-O(-) bond, even if the experimentally
      observed (17)O chemical shift of only one N-epimer is available, provided the
      (13)C chemical shifts of both N(+)-CH3 groups in the methiodide are known and
      assigned; furthermore, it can be used also for the estimation of (17)O chemical
      shifts of the N(+)-O(-) oxygens in N-epimeric pairs of N-oxides, for which
      observed (17)O data hardly become available. The second correlation is observed
      between the (13)C chemical shift of the N(+)-CH3 methyl group in the N-oxides and
      the (13)C chemical shift of the N(+)-CH3 methyl group analogously situated in the
      appropriate methiodide (r = 0.9785). It can be used for safe configuration
      assignment of the N(+)-CH3 group and, indirectly, also of the N(+)-O(-) bond in
      an amine N-oxide, even if no (17)O NMR data, and the (13)C chemical shift of only
      one N-epimer is available.

PMID- 26290174
TI  - Area-level global and local clustering of human Salmonella Enteritidis infection
      rates in the city of Toronto, Canada, 2007-2009.
AB  - BACKGROUND: Salmonella enterica serotype Enteritidis (S. Enteritidis) remains a
      major foodborne pathogen in North America yet studies examining the spatial
      epidemiology of salmonellosis in urban environments are lacking. Our ecological
      study combined a number of spatial statistical methods with a geographic
      information system to assess area-level heterogeneity of S. Enteritidis infection
      rates in the city of Toronto. METHODS: Data on S. Enteritidis infections between
      January 1, 2007 and December 31, 2009 were obtained from Ontario's surveillance
      system, and were grouped and analyzed at the forward sortation area (FSA)-level
      (an area signified by the first three characters of the postal code). Incidence
      rates were directly standardized using the FSA-level age- and sex-based standard
      population. A spatial empirical Bayes method was used to smooth the standardized
      incidence rates (SIRs). Global clustering of FSAs with high or low non-smoothed
      SIRs was evaluated using the Getis-Ord G method. Local clustering of FSAs with
      high, low, or dissimilar non-smoothed SIRs was assessed using the Getis-Ord Gi*
      and the Local Moran's I methods. RESULTS: Spatial heterogeneity of S. Enteritidis
      infection rates was detected across the city of Toronto. The non-smoothed FSA
      level SIRs ranged from 0 to 16.9 infections per 100,000 person-years (mean =
      6.6), whereas the smoothed SIRs ranged from 2.9 to 11.1 (mean = 6.3). The global
      Getis-Ord G method showed significant (p <= 0.05) maximum spatial clustering of
      FSAs with high SIRs at 3.3 km. The local Getis-Ord Gi* method identified eight
      FSAs with significantly high SIRs and one FSA with a significantly low SIR. The
      Local Moran's I method detected five FSAs with significantly high-high SIRs, one
      FSA with a significantly low-low SIR, and four significant outlier FSAs (one high
      low, and three low-high). CONCLUSIONS: Salmonella Enteritidis infection rates
      clustered globally at a small distance band, suggesting clustering of high SIRs
      in small distinct areas. This finding was supported by the local cluster
      analyses, where distinct FSAs with high SIRs, mainly in downtown Toronto, were
      detected. These areas should be evaluated by future studies to identify risk
      factors of disease in order to implement targeted prevention and control
      programs. We demonstrated the usefulness of combining several spatial statistical
      techniques with a geographic information system to detect geographical areas of
      interest for further study, and to evaluate spatial processes that influenced S.
      Enteritidis infection rates. Our study methodology could be applied to other
      foodborne disease surveillance data.

PMID- 26290176
TI  - The ZntA-like NpunR4017 plays a key role in maintaining homeostatic levels of
      zinc in Nostoc punctiforme.
AB  - Analysis of cellular response to zinc exposure provides insights into how
      organisms maintain homeostatic levels of zinc that are essential, while avoiding
      potentially toxic cytosolic levels. Using the cyanobacterium Nostoc punctiforme
      as a model, qRT-PCR analyses established a profile of the changes in relative
      mRNA levels of the ZntA-like zinc efflux transporter NpunR4017 in response to
      extracellular zinc. In cells treated with 18 MUM of zinc for 1 h, NpunR4017 mRNA
      levels increased by up to 1300 % above basal levels. The accumulation and
      retention of radiolabelled (65)Zn by NpunR4107-deficient and overexpressing
      strains were compared to wild-type levels. Disruption of NpunR4017 resulted in a
      significant increase in zinc accumulation up to 24 % greater than the wild type,
      while cells overexpressing NpunR4107 accumulated 22 % less than the wild type.
      Accumulation of (65)Zn in ZntA(-) Escherichia coli overexpressing NpunR4017 was
      reduced by up to 21 %, indicating the capacity for NpunR4017 to compensate for
      the loss of ZntA. These findings establish the newly identified NpunR4017 as a
      zinc efflux transporter and a key transporter for maintaining zinc homeostasis in
      N. punctiforme. 

PMID- 26290178
TI  - Psychotherapies for PTSD: what do they have in common?
AB  - Over the past three decades, research and clinical practice related to the field
      of traumatic stress have developed tremendously. In parallel with the steady
      accumulation of basic knowledge, therapeutic approaches have been developed to
      treat people suffering from posttraumatic stress disorder (PTSD) and other trauma
      related psychological problems. Today, a number of evidence-based treatments are
      available. They differ in various ways; however, they also have a number of
      commonalities. Given this situation, clinicians may wonder which treatment
      program to use, or more specifically, which treatment components are critical for
      a successful therapy. In this article, seven pioneers who have developed
      empirically supported psychotherapies for trauma-related disorders were asked to
      compose an essay of three parts: first, to provide a brief summary of the
      treatment they have developed; second, to identify three key interventions that
      are common and critical in treating PTSD; and third, to suggest important topics
      and future directions for research. The paper ends with a summary highlighting
      the identified commonalities (psychoeducation; emotion regulation and coping
      skills; imaginal exposure; cognitive processing, restructuring, and/or meaning
      making; emotions; and memory processes), pointing to future directions such as
      trying to better understand the underlying mechanisms of action, and developing
      treatments that are tailored to the needs of different patient groups. 

PMID- 26290177
TI  - DNA-Encoded Solid-Phase Synthesis: Encoding Language Design and Complex Oligomer
      Library Synthesis.
AB  - The promise of exploiting combinatorial synthesis for small molecule discovery
      remains unfulfilled due primarily to the "structure elucidation problem": the
      back-end mass spectrometric analysis that significantly restricts one-bead-one
      compound (OBOC) library complexity. The very molecular features that confer
      binding potency and specificity, such as stereochemistry, regiochemistry, and
      scaffold rigidity, are conspicuously absent from most libraries because isomerism
      introduces mass redundancy and diverse scaffolds yield uninterpretable MS
      fragmentation. Here we present DNA-encoded solid-phase synthesis (DESPS),
      comprising parallel compound synthesis in organic solvent and aqueous enzymatic
      ligation of unprotected encoding dsDNA oligonucleotides. Computational encoding
      language design yielded 148 thermodynamically optimized sequences with Hamming
      string distance >= 3 and total read length <100 bases for facile sequencing.
      Ligation is efficient (70% yield), specific, and directional over 6 encoding
      positions. A series of isomers served as a testbed for DESPS's utility in split
      and-pool diversification. Single-bead quantitative PCR detected 9 * 10(4)
      molecules/bead and sequencing allowed for elucidation of each compound's
      synthetic history. We applied DESPS to the combinatorial synthesis of a 75,645
      member OBOC library containing scaffold, stereochemical and regiochemical
      diversity using mixed-scale resin (160-MUm quality control beads and 10-MUm
      screening beads). Tandem DNA sequencing/MALDI-TOF MS analysis of 19 quality
      control beads showed excellent agreement (<1 ppt) between DNA sequence-predicted
      mass and the observed mass. DESPS synergistically unites the advantages of solid
      phase synthesis and DNA encoding, enabling single-bead structural elucidation of
      complex compounds and synthesis using reactions normally considered incompatible
      with unprotected DNA. The widespread availability of inexpensive oligonucleotide
      synthesis, enzymes, DNA sequencing, and PCR make implementation of DESPS
      straightforward, and may prompt the chemistry community to revisit the synthesis
      of more complex and diverse libraries.

PMID- 26290180
TI  - No Bones About It: The Challenges and Rewards of Osteopathology.

PMID- 26290179
TI  - Biocompatibility and intradiscal application of a thermoreversible celecoxib
      loaded poly-N-isopropylacrylamide MgFe-layered double hydroxide hydrogel in a
      canine model.
AB  - INTRODUCTION: Chronic low back pain due to intervertebral disc (IVD) degeneration
      is associated with increased levels of inflammatory mediators. Current medical
      treatment consists of oral anti-inflammatory drugs to alleviate pain. In this
      study, the efficacy and safety of a novel thermoreversible poly-N
      isopropylacrylamide MgFe-layered double hydroxide (pNIPAAM MgFe-LDH) hydrogel was
      evaluated for intradiscal controlled delivery of the selective cyclooxygenase
      (COX) 2 inhibitor and anti-inflammatory drug celecoxib (CXB). METHODS:
      Degradation, release behavior, and the ability of a CXB-loaded pNIPAAM MgFe-LDH
      hydrogel to suppress prostaglandin E2 (PGE2) levels in a controlled manner in the
      presence of a proinflammatory stimulus (TNF-alpha) were evaluated in vitro.
      Biocompatibility was evaluated histologically after subcutaneous injection in
      mice. Safety of intradiscal application of the loaded and unloaded hydrogels was
      studied in a canine model of spontaneous mild IVD degeneration by histological,
      biomolecular, and biochemical evaluation. After the hydrogel was shown to be
      biocompatible and safe, an in vivo dose-response study was performed in order to
      determine safety and efficacy of the pNIPAAM MgFe-LDH hydrogel for intradiscal
      controlled delivery of CXB. RESULTS: CXB release correlated to hydrogel
      degradation in vitro. Furthermore, controlled release from CXB-loaded hydrogels
      was demonstrated to suppress PGE2 levels in the presence of TNF-alpha. The
      hydrogel was shown to exhibit a good biocompatibility upon subcutaneous injection
      in mice. Upon intradiscal injection in a canine model, the hydrogel exhibited
      excellent biocompatibility based on histological evaluation of the treated IVDs.
      Gene expression and biochemical analyses supported the finding that no
      substantial negative effects of the hydrogel were observed. Safety of application
      was further confirmed by the absence of clinical symptoms, IVD herniation or
      progression of degeneration. Controlled release of CXB resulted in a
      nonsignificant maximal inhibition (approximately 35 %) of PGE2 levels in the
      mildly degenerated canine IVDs. CONCLUSIONS: In conclusion, this study showed
      biocompatibility and safe intradiscal application of an MgFe LDH-pNIPAAM
      hydrogel. Controlled release of CXB resulted in only limited inhibition of PGE2
      in this model with mild IVD degeneration, and further studies should concentrate
      on application of controlled release from this type of hydrogel in animal models
      with more severe IVD degeneration.

PMID- 26290181
TI  - Why do women choose private over public facilities for family planning services?
      A qualitative study of post-partum women in an informal urban settlement in
      Kenya.
AB  - BACKGROUND: Nearly 40% of women in developing countries seek contraceptives
      services from the private sector. However, the reasons that contraceptive clients
      choose private or public providers are not well studied. METHODS: We conducted
      six focus groups discussions and 51 in-depth interviews with postpartum women (n
      = 61) to explore decision-making about contraceptive use after delivery,
      including facility choice. RESULTS: When seeking contraceptive services, women in
      this study preferred private over public facilities due to convenience and
      timeliness of services. Women avoided public facilities due to long waits and
      disrespectful providers. Study participants reported, however, that they felt
      more confident about the technical medical quality in public facilities than in
      private, and believed that private providers prioritized profit over safe medical
      practice. Women reported that public facilities offered comprehensive counseling
      and chose these facilities when they needed contraceptive decision-support.
      Provision of comprehensive counseling and screening, including side effects
      counseling and management, determined perception of quality. CONCLUSION: Women
      believed private providers offered the advantages of convenience, efficiency and
      privacy, though they did not consistently offer high-quality care. Quality
      improvement of contraceptive care at private facilities could include technical
      standardization and accreditation. Development of support and training for side
      effect management may be an important intervention to improve perceived quality
      of care.

PMID- 26290182
TI  - Evolutionary transitions in the Asteraceae coincide with marked shifts in
      transposable element abundance.
AB  - BACKGROUND: The transposable element (TE) content of the genomes of plant species
      varies from near zero in the genome of Utricularia gibba to more than 80% in many
      species. It is not well understood whether this variation in genome composition
      results from common mechanisms or stochastic variation. The major obstacles to
      investigating mechanisms of TE evolution have been a lack of comparative genomic
      data sets and efficient computational methods for measuring differences in TE
      composition between species. In this study, we describe patterns of TE evolution
      in 14 species in the flowering plant family Asteraceae and 1 outgroup species in
      the Calyceraceae to investigate phylogenetic patterns of TE dynamics in this
      important group of plants. RESULTS: Our findings indicate that TE families in the
      Asteraceae exhibit distinct patterns of non-neutral evolution, and that there has
      been a directional increase in copy number of Gypsy retrotransposons since the
      origin of the Asteraceae. Specifically, there is marked increase in Gypsy
      abundance at the origin of the Asteraceae and at the base of the tribe
      Heliantheae. This latter shift in genome composition has had a significant impact
      on the diversity and abundance distribution of TEs in a lineage-specific manner.
      CONCLUSIONS: We show that the TE-driven expansion of plant genomes can be
      facilitated by just a few TE families, and is likely accompanied by the
      modification and/or replacement of the TE community. Importantly, large shifts in
      TE composition may be correlated with major of phylogenetic transitions.

PMID- 26290183
TI  - Molecular characterization of extended-spectrum beta-lactamases (ESBLs) produced
      by clinical isolates of Acinetobacter baumannii in Saudi Arabia.
AB  - BACKGROUND: Acinetobacter baumannii is a common opportunistic pathogen that
      causes major nosocomial infections in hospitals. In this study, we hypothesized a
      high prevalence of A. baumanni ESBL (extended-spectrum beta-lactamase) among all
      collected isolates. METHODS: A. baumannii isolates (n = 107) from ICU (Intensive
      care unit) of local hospitals in Makkah were phenotypically and genotypically
      characterized. The identity and antibiotic susceptibility of A. baumannii strains
      were determined using the Vitek-2 system. The identified ESBL producers were
      further analyzed by PCR and sequencing followed by MLST typing. bla TEM , bla SHV
      , and the bla CTX-M-group genes 1, 2, 8, 9, and 25 were investigated.
      Furthermore, bla OXA51-like and bla OXA23-like genes were also examined in the
      carbapenem-resistant A. baumannii isolates. RESULTS: Our data indicated a high
      prevalence of A. baumannii ESBL producers among the collected strains. Of the 107
      A. baumannii isolates, 94 % were found to be resistant to cefepime and
      ceftazidime, and aztreonam using the Vitek 2 system. The genes detected encoded
      TEM, OXA-51-like and OXA-23-like enzymes, and CTX-M-group proteins 1, 2, 8, 9,
      and 25. MLST typing identified eight sequence type (ST) groups. The most dominant
      STs were ST195 and ST557 and all of them belong to worldwide clonal complex (CC)
      2. CONCLUSIONS: This study has shown that there is a high prevalence of
      antimicrobial resistance in A. baumannii. The diversity of STs may suggest that
      new ESBL strains are constantly emerging. The molecular diversity of the ESBL
      genes in A. baumannii may have contributed to the increased antimicrobial
      resistance among all isolates.

PMID- 26290184
TI  - Expression of AIM2 is correlated with increased inflammation in chronic hepatitis
      B patients.
AB  - BACKGROUND: The absent in melanoma 2 (AIM2), a cytosolic dsDNA inflammasome, can
      be activated by viral DNA to trigger caspase-1. Its role in immunopathology of
      chronic hepatitis B and C virus (HBV, HCV) infection is still largely unclear. In
      this study, the expression AIM2, and its downstream cytokines, caspase-1, IL-18
      and IL-1beta, in liver tissue of patients with chronic hepatitis B and C (CHB,
      CHC) were investigated. METHODS: A total of 70 patients diagnosed with chronic
      hepatitis were enrolled, including 47 patients with CHB and 23 patients with CHC.
      A liver biopsy was taken from each patient, and immunohistochemistry was used to
      detect the expression of AIM2 and inflammatory factors caspase-1, IL-18, and IL
      1beta in the biopsy specimens. The relationship between AIM2 expression and these
      inflammatory factors was analyzed. RESULTS: The expression of AIM2 in CHB
      patients (89.4 %) was significantly higher than in CHC patients (8.7 %), and
      among the CHB patients, the expression of AIM2 was significantly higher in the
      high HBV replication group (HBV DNA >= 1 * 10(5)copies/mL) than in the low HBV
      replication group (HBV DNA < 1 * 10(5)copies/mL). The expression of AIM2 was also
      correlated with HBV-associated inflammatory activity in CHB patients
      statistically. Additionally, AIM2 levels were positively correlated with the
      expression of caspase-1, IL-1beta and IL-18 in CHB patients, which implied that
      the AIM2 expression is directly correlated with the inflammatory activity
      associated with CHB. CONCLUSIONS: AIM2 upregulation may be a component of HBV
      immunopathology. The underlying mechanism and possible signal pathway warrant
      further study.

PMID- 26290185
TI  - TWO FACTORS INFLUENCING DOSE RECONSTRUCTION IN LOW DOSE RANGE: THE VARIABILITY OF
      BKG INTENSITY ON ONE INDIVIDUAL AND WATER CONTENT.
AB  - A fast and accurate retrospective dosimetry method for the triage is very
      important in radiation accidents. Electron paramagnetic resonance (EPR)
      fingernail dosimetry is a promising way to estimate radiation dose. This article
      presents two factors influencing dose reconstruction in low dose range: the
      variability of background signal (BKG) intensity on one individual and water
      content. Comparing the EPR spectrum of dried and humidified fingernail samples,
      it is necessary to add a procedure of dehydration before EPR measurements, so as
      to eliminate the deviation caused by water content. Besides, the BKGs of
      different fingers' nails are not the same as researchers thought previously, and
      the difference between maximum and minimum BKG intensities of one individual can
      reach 55.89 %. Meanwhile, the variability of the BKG intensity among individuals
      is large enough to impact precise dose reconstruction. Water within fingernails
      and instability of BKG are two reasons that cause the inaccuracy of radiation
      dose reconstruction in low-dosage level.

PMID- 26290186
TI  - "You Get Reminded You're a Sick Person": Personal Data Tracking and Patients With
      Multiple Chronic Conditions.
AB  - BACKGROUND: Consumer health information technologies (HIT) that encourage self
      tracking, such as diet and fitness tracking apps and disease journals, are
      attracting widespread interest among technology-oriented consumers (such as
      "quantified self" advocates), entrepreneurs, and the health care industry. Such
      electronic technologies could potentially benefit the growing population of
      patients with multiple chronic conditions (MCC). However, MCC is predominantly a
      condition of the elderly and disproportionately affects the less affluent, so it
      also seems possible that the barriers to use of consumer HIT would be
      particularly severe for this patient population. OBJECTIVE: Our aim was to
      explore the perspectives of individuals with MCC using a semistructured interview
      study. Our research questions were (1) How do individuals with MCC track their
      own health and medical data? and (2) How do patients and providers perceive and
      use patient-tracked data? METHODS: We used semistructured interviews with
      patients with multiple chronic diseases and providers with experience caring for
      such patients, as well as participation in a diabetes education group to
      triangulate emerging themes. Data were analyzed using grounded theory and
      thematic analysis. Recruitment and analysis took place iteratively until thematic
      saturation was reached. RESULTS: Interviews were conducted with 22 patients and 7
      health care providers. The patients had an average of 3.5 chronic conditions,
      including type 2 diabetes, heart disease, chronic pain, and depression, and had
      regular relationships with an average of 5 providers. Four major themes arose
      from the interviews: (1) tracking this data feels like work for many patients,
      (2) personal medical data for individuals with chronic conditions are not simply
      objective facts, but instead provoke strong positive and negative emotions, value
      judgments, and diverse interpretations, (3) patients track for different
      purposes, ranging from sense-making to self-management to reporting to the
      doctor, and (4) patients often notice that physicians trust technologically
      measured data such as lab reports over patients' self-tracked data. CONCLUSIONS:
      Developers of consumer health information technologies for data tracking (such as
      diet and exercise apps or blood glucose logs) often assume patients have
      unlimited enthusiasm for tracking their own health data via technology. However,
      our findings potentially explain relatively low adoption of consumer HIT, as they
      suggest that patients with multiple chronic illnesses consider it work to track
      their own data, that the data can be emotionally charged, and that they may
      perceive that providers do not welcome it. Similar themes have been found in some
      individual chronic diseases but appeared more complex because patients often
      encountered "illness work" connected to multiple diseases simultaneously and
      frequently faced additional challenges from aging or difficult comorbidities such
      as chronic pain, depression, and anxiety. We suggest that to make a public health
      impact, consumer HIT developers should engage creatively with these pragmatic and
      emotional issues to reach an audience that is broader than technologically
      sophisticated early adopters. Novel technologies are likely to be successful only
      if they clearly reduce patient inconvenience and burden, helping them to
      accomplish their "illness work" more efficiently and effectively.

PMID- 26290187
TI  - Redundancy complicates the definition of essential   genes for vaccinia virus.
AB  - Vaccinia virus (VACV) genes are characterized as either essential or non
      essential for growth in culture. It seems intuitively obvious that if a gene can
      be deleted without imparting a growth defect in vitro it does not have a function
      related to basic replication or spread. However, this interpretation relies on
      the untested assumption that there is no redundancy across the genes that have
      roles in growth in cell culture. First, we provide a comprehensive summary of the
      literature that describes the essential genes of VACV. Next, we looked for
      interactions between large blocks of non-essential genes located at the ends of
      the genome by investigating sets of VACVs with large deletions at the genomic
      termini. Viruses with deletions at either end of the genome behaved as expected,
      exhibiting only mild or host-range defects. In contrast, combining deletions at
      both ends of the genome for the VACV Western Reserve (WR) strain caused a
      devastating growth defect on all cell lines tested. Unexpectedly, we found that
      the well-studied VACV growth factor homologue encoded by C11R has a role in
      growth in vitro that is exposed when 42 genes are absent from the left end of the
      VACV WR genome. These results demonstrate that some non-essential genes
      contribute to basic viral growth, but redundancy means these functions are not
      revealed by single-gene-deletion mutants.

PMID- 26290188
TI  - A Highly Efficient Sensor Platform Using Simply Manufactured Nanodot Patterned
      Substrates.
AB  - Block copolymer (BCP) self-assembly is a low-cost means to nanopattern surfaces.
      Here, we use these nanopatterns to directly print arrays of nanodots onto a
      conducting substrate (Indium Tin Oxide (ITO) coated glass) for application as an
      electrochemical sensor for ethanol (EtOH) and hydrogen peroxide (H2O2) detection.
      The work demonstrates that BCP systems can be used as a highly efficient,
      flexible methodology for creating functional surfaces of materials. Highly dense
      iron oxide nanodots arrays that mimicked the original BCP pattern were prepared
      by an 'insitu' BCP inclusion methodology using poly(styrene)-block-poly(ethylene
      oxide) (PS-b-PEO). The electrochemical behaviour of these densely packed arrays
      of iron oxide nanodots fabricated by two different molecular weight PS-b-PEO
      systems was studied. The dual detection of EtOH and H2O2 was clearly observed.
      The as-prepared nanodots have good long term thermal and chemical stability at
      the substrate and demonstrate promising electrocatalytic performance. 

PMID- 26290189
TI  - Lack of epidermal growth factor receptor (EGFR)-activating mutations in triple
      negative breast cancer in China.

PMID- 26290190
TI  - Politics of Science: Unwarranted Encounters.
AB  - This communication highlights a very pertinent and recent case of an erroneous
      representation of the Indian borders in an article 'India by the numbers' by
      Richard Van Noorden in Nature ( http://www.nature.com/news/india-by-the-numbers
      1.17519 ) where a considerable part of the Jammu and Kashmir State of India is
      missing in the map incorporated in the article. The article received a series of
      comments showing disappointment on the issue and a need for the correction to the
      depicted Indian borders. The editor instead of making corrections to the map has
      issued a statement that 'the map shows land areas currently administered by the
      Indian Government', that in no way can be considered as an acceptable argument.
      We wish the focus of this well written article had remained on science rather
      than introducing unnecessary controversies.

PMID- 26290191
TI  - Promoting positive states: the effect of early human handling on play and
      exploratory behaviour in pigs.
AB  - It is known that tactile stimulation (TS) during ontogeny modifies brain
      plasticity and enhances the motor and cognitive skills. Our hypothesis was that
      early handling including TS would increase play and exploratory behaviour in
      commercial pigs under standardized test conditions. Piglets from 13 litters were
      subjected to three handling treatments from 5 to 35 days of age: all the piglets
      were handled (H), none of the piglets were handled (NH) or half of the piglets in
      the litter were handled (50/50). At 42 days of age, the pigs' behaviour was
      observed in pairs in a novel pen with a 'toy' (tug rope). The main results were
      that more locomotor play was performed by pigs from litters where all or half of
      them had been handled, whereas social exploratory behaviour was more pronounced
      in pigs from litters where half of them had been handled. Although behaviour was
      affected by the interaction of treatment with sex or with weight category, we
      propose that the handling procedure does seem to have acted to increase locomotor
      skills and that handling half of the piglets in the litter may have triggered a
      series of socio-emotional interactions that were beneficial for the whole group. 

PMID- 26290192
TI  - Genomewide investigation of adaptation to harmful algal blooms in common
      bottlenose dolphins (Tursiops truncatus).
AB  - Harmful algal blooms (HABs), which can be lethal in marine species and cause
      illness in humans, are increasing worldwide. In the Gulf of Mexico, HABs of
      Karenia brevis produce neurotoxic brevetoxins that cause large-scale marine
      mortality events. The long history of such blooms, combined with the potentially
      severe effects of exposure, may have produced a strong selective pressure for
      evolved resistance. Advances in next-generation sequencing, in particular
      genotyping-by-sequencing, greatly enable the genomic study of such adaptation in
      natural populations. We used restriction site-associated DNA (RAD) sequencing to
      investigate brevetoxicosis resistance in common bottlenose dolphins (Tursiops
      truncatus). To improve our understanding of the epidemiology and aetiology of
      brevetoxicosis and the potential for evolved resistance in an upper trophic level
      predator, we sequenced pools of genomic DNA from dolphins sampled from both
      coastal and estuarine populations in Florida and during multiple HAB-associated
      mortality events. We sequenced 129 594 RAD loci and analysed 7431 single
      nucleotide polymorphisms (SNPs). The allele frequencies of many of these
      polymorphic loci differed significantly between live and dead dolphins. Some loci
      associated with survival showed patterns suggesting a common genetic-based
      mechanism of resistance to brevetoxins in bottlenose dolphins along the Gulf
      coast of Florida, but others suggested regionally specific mechanisms of
      resistance or reflected differences among HABs. We identified candidate genes
      that may be the evolutionary target for brevetoxin resistance by searching the
      dolphin genome for genes adjacent to survival-associated SNPs. 

PMID- 26290193
TI  - Powder Production and Particle Engineering for Dry Powder Inhaler Formulations.
AB  - Dry powder inhalers have become increasingly attractive for pulmonary delivery of
      locally and systemically effective medications. In comparison to the liquid
      counterparts, such as nebulisation and pressurised metered dose inhalers, the
      powder form generally offers better chemical stability, improved portability and
      potentially superior patient adherence. Currently, the aerosol performance
      between dry powder inhalers varies to a large extent due to differences in the
      design of inhaler device and formulation. The particulate properties have a
      significant influence on the inter-particle interactions, which impacts on the
      aerosolisation of the inhaled powder. In this review, critical particulate
      properties that affect aerosol performance are discussed. Recent advances in
      powder production and particle engineering techniques are also assessed, aiming
      to develop new inhaled powder formulations or improve the aerosolisation
      efficiency of existing products. 

PMID- 26290194
TI  - Discrete Modelling of Powder Dispersion in Dry Powder Inhalers - A Brief Review.
AB  - The performance of a dry powder inhaler (DPI) depends on powder properties as
      well as the air and particle flows in the device. The main principle of powder
      dispersion is to overcome the inter-particle cohesion using various dispersion/
      de-agglomeration forces. While different dispersion mechanisms have been
      identified, their relative importance under different conditions is less clear.
      The lack of understanding of these mechanisms is a major obstacle to the advance
      of pharmaceutical powder aerosol technology. This paper briefly reviews our
      recent effort in developing a combined computational fluid dynamics (CFD) and
      discrete element method (DEM) approach to gain such pivotal information.
      Dispersions under various specifically designed conditions were simulated to exam
      the role of individual dispersion mechanism. The air and particle flows were
      analysed at the particle scale and linked to dispersion performance characterised
      by fine particle fraction (FPF). In addition, the dispersion mechanisms of both
      drug only and carrier based formulations in a commercial inhaler were studied.
      Our work shows that the approach has the potential to develop a theoretical
      framework for designing new DPIs. 

PMID- 26290195
TI  - Formulation Approaches to Overcome Biopharmaceutical Limitations of Inhaled
      Peptides/Proteins.
AB  - The pulmonary dosing route has been advocated as an attractive alternative to
      injection and oral administration for the systemic delivery of therapeutic
      peptides and proteins. The lung possesses many favorable physiological
      characteristics for systemic absorption of inhaled peptides/proteins, so
      inhalable formulation systems of these drugs have generated considerable interest
      as a valid and non-invasive dosing approach. A major obstacle to the widespread
      use of inhalation therapies for many peptides/proteins is the limited
      bioavailability and thereby insufficient therapeutic outcomes because of
      biopharmaceutical challenges such as rapid pulmonary clearance, limited pulmonary
      deposition, delayed dissolution in lung environment, poor membrane permeability,
      and low metabolic stability. A better understanding of the biopharmaceutical
      properties of inhaled peptides/proteins would be indispensable to overcome these
      drawbacks with the aid of strategic drug delivery systems and chemical synthesis
      of new derivatives based on structure-activity relationship information, possibly
      leading to improved therapeutic potential of pharmaceutical products. The present
      paper reviews biopharmaceutical properties of inhaled peptides/proteins, with a
      focus on the pharmacokinetic fate of inhaled peptides/proteins and critical
      determinants of therapeutic potential. The emphasis in this mini-review will also
      be on viable formulation approaches for breakthroughs beyond the
      biopharmaceutical limitations of inhalation therapy with peptides/proteins. 

PMID- 26290197
TI  - Chinese Medicine in Inhalation Therapy: A Review of Clinical Application and
      Formulation Development.
AB  - Chinese medicine (CM) in inhalation therapy has a long history of applications
      since ancient China in the forms of smoke, steam vapor, medicated pillows and
      aromatic sachets. Over the years, thousands of clinical treatments involving the
      inhalation of CMs have been reported for the treatment of respiratory disease.
      Shuanghuanglian, Yuxingcao and Qingkailing are primarily applied in pneumonia and
      bronchitis. At present, metered dose inhalation (MDI), aromatic inhalation and
      nebulized inhalation are used extensively in practice. In particular, nebulized
      CM for the treatment of respiratory diseases has been applied as a noninvasive
      route with reduced serious adverse reactions and is equivalent to or more
      efficacious than its intravenous counterparts. Although nebulized CM is widely
      used in clinical practice, only three MDI and five aromatic inhalations of CM
      products have been approved by the China Food and Drug Administration (CFDA), and
      no products in the form of a dry powder inhaler (DPI) or in dosage forms intended
      for nebulization have been reported. The development of formulations for CM has
      focused on improving the aerodynamic performance of the particles prepared by
      spray drying, enhancing the bioavailability and local concentration in the
      respiratory tract, and increasing the mucoadhesion and sustained release of the
      CM upon the incorporation of novel excipients. New devices, including MDI and
      nebulizer devices, have been developed for the delivery of the above-mentioned
      particles to the pulmonary system. Although the development of CM inhalation
      products to meet the international quality standards is facing a number of
      challenges, the inhalation of CMs show great potential for further exploration,
      particularly as an alternative route to IV infusion for the treatment of
      respiratory diseases. 

PMID- 26290196
TI  - Use of Extrathoracic Deposition Models for Patient-Specific Dose Estimation
      during Inhaler Design.
AB  - The lung dose of inhaled pharmaceutical aerosol that an individual will receive
      from an inhaler can now be more accurately estimated in light of recent
      extrathoracic deposition modeling that has correlated characteristic airway
      dimensions with deposition. This paper first summarizes the current state of
      extrathoracic deposition models, including recent developments that have
      quantified the effects of aerosol electrostatics and inhaler mouthpiece diameter
      on deposition. A generalized equation for predicting extrathoracic deposition in
      different subjects is then developed and average characteristic airway dimensions
      representative of different age groups are indicated. A methodology is then
      presented to predict the lung dose per unit body surface area individuals will
      receive from an inhaler. A sample calculation shows that a typical 10-year-old
      child subject would receive a lower lung dose per unit body surface area than an
      adult subject inhaling through the same inhaler at the same 90 L min-1 flow rate,
      due to greater extrathoracic deposition in the child. In order to provide an
      equivalent lung dose per unit body surface area to the child as to the adult, an
      inhaler particle size adjustment is specified. Finally, the use of idealized
      geometries for developing inhaler-specific empirical correlations and improving
      upon inhaler design is outlined. 

PMID- 26290198
TI  - Electrostatics of Pharmaceutical Aerosols for Pulmonary Delivery.
AB  - This paper provides a review on key research findings in the rapidly developing
      area of pharmaceutical aerosol electrostatics. Solids and liquids can become
      charged without electric fields, the former by contact or friction and the latter
      by flowing or spraying. Therefore, charged particles and droplets carrying net
      charges are produced from pharmaceutical inhalers (e.g. dry powder inhalers,
      metered dose inhalers, and nebulisers) due to the mechanical processes involved
      in aerosolisation. The charging depends on many physicochemical factors, such as
      formulation composition, solid state properties, inhaler material and design, and
      relative humidity. In silico, in vitro, and limited in vivo studies have shown
      that electrostatic charges may potentially influence particle deposition in the
      airways. However, the evidence is not yet conclusive. Furthermore, there are
      currently no regulatory requirements on the characterisation and control of the
      electrostatic properties of inhaled formulations. Besides the need for further
      investigations on the relationship between physicochemical factors and charging
      characteristics of the aerosols, controlled and detailed in vivo studies are also
      required to confirm whether charges can affect particle deposition in the
      airways. Since pharmaceutical aerosol electrostatics is a relatively new research
      area, much remains to be explored. Thus there is certainly potential for
      development. New findings in the future may contribute to the advancement of
      pharmaceutical aerosol formulations and respiratory drug delivery. 

PMID- 26290199
TI  - Inhaled Formulation Design for the Treatment of Lung Infections.
AB  - Lung infections may be bacterial, viral or fungal and they are typically treated
      with oral or parenteral antibiotics. Inhaled dry powder formulations offer unique
      opportunities for treating lung infections with enhanced effectiveness and
      stability. Since drug delivery to the lungs requires chronic and repeated
      administration of larger amounts of therapeutics, dry powder formulations are
      attractive alternatives to deliver drugs directly to the lungs as they are not
      limited by solubility issues and they are regarded as being more stable than
      liquid dosage forms. This state-of-the-art review presents the use of inhaled
      formulations for tuberculosis as a main focus, but also for other diseases such
      as bronchiectasis, chronic obstructive pulmonary disease (COPD), pneumonia and
      respiratory infections occurring as complications during lung transplants.
      Opportunities for the use of inhaled therapies and other respiratory diseases or
      as prevention or antidotes against warfare agents are offered. Typical and novel
      inhaled formulations that have been used as well as preclinical and clinical
      studies and evaluation of these inhaled therapies are discussed for each disease
      state. Lastly, the use of inhaled therapies as an alternative to end the
      emergence of drug resistant strains is discussed along with the risks of
      increasing these resistant strains if the inhaled therapy is not designed based
      on dosing regimens established by wellplanned pharmacokinetic and pharmacodynamic
      studies. 

PMID- 26290200
TI  - A Review of Methods for Evaluating Particle Stability in Suspension Based
      Pressurized Metered Dose Inhalers.
AB  - Advances in particle engineering techniques, such as spray drying, freeze drying
      and supercritical fluid precipitation, have greatly enhanced the ability to
      control the structure, morphology, and solid state phase of inhalable sized
      particles (1 - 5 um) for formulation in pressurized metered dose inhalers (pMDI).
      To optimize the properties of these engineered particles for formulation in
      hydrofluoroalkane propellants (HFA 134a / 227) it is necessary to measure both
      bulk and individual particle properties before, after, and during formulation.
      This review examines established and recently developed methods for evaluating a
      variety of particle properties including but not limited to size, surface and
      internal morphology, chemical composition, and solid state phase. Novel methods
      for evaluating particle physical and chemical stability directly in propellant or
      similar environments are also discussed. 

PMID- 26290201
TI  - Surface Energy Determined by Inverse Gas Chromatography as a Tool to Investigate
      Particulate Interactions in Dry Powder Inhalers.
AB  - Dry powder inhalers (DPIs) usually contain drug particles <6 um which agglomerate
      and/ or adhere on the surfaces of large carriers particles. The detachment of
      drug particles from carriers and de-agglomeration of drug particles into primary
      particles is essential for drug deposition in the deep lung. These processes are
      influenced by the surface energy of particles. Inverse gas chromatography (IGC)
      has been used to determine the surface energy of powder particles used in DPI to
      characterize materials and to understand aerosolization behaviour. Early studies
      used an infinite dilution technique to determine nonpolar surface energy and free
      energy of adsorption for polar interactions separately. Although some
      correlations were observed with the change in nonpolar surface energy before and
      after micronization, milling and storage, a lack of consistency in the change of
      free energy of adsorption was common. Moreover, a consistent relationship between
      complex de-agglomeration behaviour and surface energy has not been established
      and there are even some examples of negative correlation. In fact, nonpolar
      surface energy at infinite dilution is an incomplete representation of powder
      surface characteristics. The techniques for measuring polar surface energy, total
      surface energy and surface energy distribution have provided more revealing
      information about surface energetics of powders. Surface energy distributions
      determined by IGC or surface energy analyser have been successfully used to
      understand energetic heterogeneity of surfaces, characterize different polymorphs
      and understand changes due to micronization, structural relaxation, dry coating
      and storage. Efforts have been made to utilize surface energy distribution data
      to calculate powder strength distribution and to explain complex de-agglomeration
      behaviour of DPI formulations. 

PMID- 26290202
TI  - Dry Powder Formulation of Plasmid DNA and siRNA for Inhalation.
AB  - Nucleic acid therapeutics has huge potential for the treatment of a wide range of
      diseases including respiratory diseases. Plasmid DNA (pDNA) and small interfering
      RNA (siRNA) are the two most widely investigated nucleic acids for therapeutic
      development. However, efficient and safe delivery of nucleic acids is still a
      major hurdle in translating nucleic acid therapy into clinical practice. For the
      treatment of respiratory diseases, administration via inhalation is the most
      direct and effective way to deliver therapeutic nucleic acids to the lungs.
      Although liquid aerosol formulation is investigated in most of the studies, it is
      not desirable in terms of maintaining the stability of nucleic acid especially
      during long-term storage. This problem could be circumvented by formulating the
      therapeutic nucleic acids into dry powder for inhalation, and should be
      considered as the future direction of developing inhalable nucleic acids. In this
      review, the three major particle engineering methods investigated for the
      preparation of inhalable pDNA and siRNA formulations, including spray drying
      (SD), spray freeze drying (SFD) and supercritical fluid (SFC) drying, are
      discussed and compared. Moreover, common assessment methods and the challenges of
      evaluating the biological activities of inhalable nucleic acid powders are also
      reviewed. 

PMID- 26290203
TI  - The Role of Inspiratory Pressures in Determining the Flow Rates Though Dry Powder
      Inhalers; A Review.
AB  - Dry powder inhalers are one of the most popular devices for delivering medication
      directly to the lungs of patients. Both for local action and when using the lungs
      as a portal of entry into the systemic circulation. Dry powder inhalers rely on
      the patient's inspiratory effort to supply the energy for the device to
      effectively deliver medication. In this respect they are limited by the airway
      pressures that a patient can generate with their respiratory muscles. In this
      review we focus on a simple model outlining the variables influencing respiratory
      pressure and review the literature on inspiratory flow rates in patients with
      respiratory disease. The main determinants of the capability to generate the
      pressure necessary to effectively use a dry powder inhaler are shown to be age
      and gender, not disease or disease severity. 

PMID- 26290204
TI  - Alginates in Pharmaceutics and Biomedicine: Is the Future so Bright?
AB  - Alginate represents one of the most appealing biopolymers for pharmaceutical and
      biomedical applications. Alginate as a biomaterial for clinical use has been
      established, although not free from issues. Here we provide a critical review on
      some of the main recent advances in alginate research in drug delivery and its
      prominent role in cell microencapsulation for the treatment of diseases, such as
      type 1 diabetes mellitus. A brief description of the basic properties of the
      polymer will be provided as well. Based on our experience and contributions, as
      well as wide research in the field, the correlation between physicochemical and
      biological properties of alginate systems and clinical outcomes will be
      investigated and discussed to address the actual future clinical impact of
      alginatebased delivery strategies. 

PMID- 26290205
TI  - Cyclodextrin-Based Delivery Systems for Arthritic Diseases: From Development to
      Experimental Therapeutics.
AB  - Arthritics diseases, such as rheumatoid arthritis and osteoarthritis are chronic
      inflammatory and one of the most prevalent health conditions that cause
      disability (pain and functional limitation of joints). Despite the research
      advances, the treatment of those pathological conditions remains ineffective,
      since the pharmacological therapy is palliative, reducing only the symptoms and,
      in some cases, the chronic progression of the disease. In this context, the
      development of new formulations for controlled release would be interesting for
      reducing the number of injections and would also increase the patient compliance.
      In this article, we present a review of the cyclodextrin (CD)-based delivery
      systems focusing from conventional guest-host inclusion complexes and CD
      polysulphates, until supramolecular architectures such as drug-CD-polymers
      conjugates, pseudorotaxanes, hydrogels as well as double-carrier systems and
      other systems. In particular, this article focuses the main CD-based delivery
      systems described in the literature emphasizing their possible administration by
      intra-articular route on the treatment of arthritic diseases, concentrating on
      their development and also performance as in vivo experimental therapeutic
      systems. 

PMID- 26290206
TI  - Polysaccharides as Bacterial Antiadhesive Agents and "Smart" Constituents for
      Improved Drug Delivery Systems Against Helicobacter pylori Infection.
AB  - The standard eradication treatment of the hostile Helicobacter pylori (H. pylori)
      stomach infection is facing increasing alarming antibiotic resistance worldwide
      and calls for alternative strategies to the use of antibiotics. One new
      perspective in this direction is cytoprotective compounds for targeted prevention
      of the adhesion of the bacteria to the stomach host cell and to inhibit the
      bacterial cell-cell communication via quorum sensing by specific inhibitors.
      Bacterial adhesion of H. pylori to the host cells is mainly mediated by
      carbohydrate-protein interactions. Therefore, the use of polyvalent
      carbohydrates, (e.g. plant-derived polysaccharides), as potential antiadhesive
      compounds, seems to be a promising tool to prevent the initial docking of the
      bacterium to the stomach cells. Polysaccharides are common constituents of daily
      food, either as starch or as dietary fiber and often also function as excipients
      for galenic drug-delivery formulations. In addition, polysaccharides with defined
      pharmacodynamics action against bacterial outer membrane proteins can have
      potential as therapeutic tools in the treatment of bacterial infections. Some
      polysaccharides are known to possess antibacterial properties against gram
      positive bacteria, others to inhibit bacterial colonization by blocking specific
      carbohydrate receptors involved in host-bacteria interaction. This mode of action
      is advocated as alternative antiadhesion therapy. Ongoing research is also
      seeking for polysaccharide-based nanoformulations with potential for local drug
      delivery at the stomach as novel H. pylori therapies. These approaches pose
      challenges concerned with the stability of the nanomaterials in the harsh
      conditions of the gastric environment and their capacity to adhere to the stomach
      mucosa. In a global scenario, geographical diversity and social habits, namely
      lifestyle and dietary factors, influence the prevalence of the H. pylori
      associated diseases and their severity. In this context, the exploration of the
      biological activity of plant-derived products or polysaccharides commonly present
      in foods is increasingly becoming more and more attractive. This review aims to
      present the current state-of-the-art on the antiadhesive capacity of different
      polysaccharide families, on polysaccharide-based nanosystems and the proof-of
      concept evidence of their potential use as alternative medicines against H.
      pylori. 

PMID- 26290207
TI  - Activation of Macrophages: Establishing a Role for Polysaccharides in Drug
      Delivery Strategies Envisaging Antibacterial Therapy.
AB  - Infectious diseases are an important health concern, as several pathogens have
      developed the ability to survive inside phagocytic cells (mostly macrophages),
      encountered at early infection stages, using these cells as trojan horses. In
      fact, in several cases macrophages have become a nutrient reservoir that helps
      pathogens to grow in number and spread. It is frequent that conventional
      therapeutic schedules include long periods of drug intake, at high doses, in some
      cases leading to severe side effects and clinical relapses due to prolonged
      intake, along with an increased risk for the development of antibiotic
      resistances. Therefore, there is a compelling need to develop new therapeutic
      strategies providing a targeted drug delivery to macrophages. These cells have
      unique surface receptors that might recognise preferentially several
      polysaccharide moieties present on the surface of infecting organisms, including
      in the bacterial cell wall. Benefiting from a similar composition regarding the
      referred moieties, polysaccharides might be good candidates to compose the matrix
      of drug carriers aimed at macrophage targeting, as they can use the same
      recognition pathways of the infecting organisms. This review describes the
      features and the role of macrophages in infectious conditions, while addressing
      their potential as therapeutic targets and unravelling the prominent role of
      polysaccharides as matrix materials of drug delivery systems developed for the
      therapy of infectious diseases. 

PMID- 26290208
TI  - Polysaccharide-Based Nanocarriers for Ocular Drug Delivery.
AB  - Obtaining successful ocular formulations able to support an efficient drug
      concentration at the target tissue for an appropriate period of time is an
      interesting challenge for modern pharmaceutical technology. In this sense,
      nanotechnology is one of the available strategies to obtain a drug carrier system
      that allows access to different compartments of the eye in order to deliver drugs
      to the desired site. Biodegradable polymers such as polysaccharides are promising
      biomaterials for the production of biocompatible and biodegradable nanocarriers
      (NCs). Different types of polysaccharide NCs are capable of improving the
      transport of drugs after ocular application and they can be either polysaccharide
      matrix carriers or polysaccharide-coated carriers, depending on whether
      polysaccharide is used as a matrix or as a coating, respectively. This review
      focuses on recent advances achieved by polysaccharide-based NCs for the treatment
      of ocular disorders. 

PMID- 26290209
TI  - Polysaccharide-Based Nanobiomaterials as Controlled Release Systems for Tissue
      Engineering Applications.
AB  - Polysaccharides belong to a special class of biopolymers that has been used in
      different areas of research and technology for some years now. They present
      distinctive features attractive for the biomedical field. Among others, as
      extracted from natural sources, these materials are usually biocompatible and
      possess a significant ability to absorb water. Moreover, they can be conveniently
      modified by chemical means so as to display improved biological and
      physicochemical properties. The last but not the least, they are abundant in the
      natural Extracellular Matrix (ECM) and have a tremendous affinity for different
      endogenous macromolecules. Accordingly, these particular materials constitute
      outstanding candidates for a variety of biomimetic approaches entailing the
      entrapment/stabilization of bioactive molecules (e.g. growth factors, siRNA, and
      DNA) that could be delivered and have an effect on relevant cellular mechanisms,
      such as gene expression and cell viability, -proliferation, and -differentiation.
      This review will explore the current status of nano-scale drug delivery devices
      based on polysaccharides that could be used in tissue engineering and
      regenerative medicine (TERM). Aiming to contextualize the topics here discussed,
      especially for non-experts in the field, section 1 (Introduction) will present a
      brief overview of TERM and the principal polysaccharides herein employed. In
      order to get a broader perspective on both issues, this section will include a
      brief description of non-nanometric systems with relevant characteristics for
      TERM, such as injectable microparticles and macroscopic hydrogels, just to cite a
      few. Section 2 will illustrate the contributions of nanotechnology to the
      development of TERM, in particular to the development of biomimetic systems
      capable of replicating the natural, endogenous ECMs. Next, sections 3 to 6 will
      describe representative systems in the nanometric scale presenting 0D
      (nanoparticles), 1D (nanorods and nanowires), 2D (thin coatings/films or
      multilayered systems), and 3D (woven nanofibrillar mats and meshes)
      configurations, respectively. Special attention will be paid on how nanometric
      constructs with these configurations can be used as model systems in TERM to
      understand and/or manipulate biological functions at the cellular level. Finally,
      section 7 will provide an outlook on future perspectives in the field. Overall,
      the review is intended to constitute a critical source of information relative to
      the current status of polysaccharide- based biomaterials for TERM, in particular
      those at the nanometric scale. 

PMID- 26290210
TI  - Polysaccharide Colloids as Smart Vehicles in Cancer Therapy.
AB  - Cancer disease is one of the leading causes of morbidity and mortality worldwide,
      with approximately 14 million new cases and around 8 million cancer-related
      deaths yearly. Estimates expect to increase these figures over the next few
      years. Therefore, it is very important to develop more effective and targeted
      therapies. Polysaccharides are widely used for biomedical and pharmaceutical
      applications due to their interesting properties, and can be utilised in the
      production of nanovehicles for drug delivery, since they frequently extend the
      half-life and improve the stability of chemotherapeutic agents in bloodstream
      allowing them to reach the tumour tissue. Moreover, polysaccharide-based
      nanovehicles are generally expected to increase the therapeutic benefit by
      reducing the undesired side effects and promoting a more efficient cellular
      uptake. Here, we highlight the application of various polysaccharides as
      nanovehicles in cancer therapy, focusing mainly on in vivo applications and
      describing the main advantages of each designed system in a critical way. The use
      of different polysaccharides interacting with metal nanoparticles to develop new
      nanovehicles for cancer therapy will also be discussed. 

PMID- 26290211
TI  - Polysaccharide Based Formulations for Mucosal Drug Delivery: A Review.
AB  - There has been increased interest in novel drug delivery systems to be
      administered via mucosal routes as an alternative to the currently used
      traditional routes such as parenteral (injections) and oral routes of
      administration. This is due to the several advantages they offer including
      avoiding first pass metabolism in the liver for oral administration and local
      activity which avoids the need for high systemic doses. To achieve the foregoing
      objectives, bioadhesive vehicles are required that ensure prolonged residence
      time to achieve systemic bioavailability via substantial drug absorption or
      significant drug concentration for local action. The drug delivery system is also
      required to be non-deleterious to the site of application and be well tolerated
      by vulnerable groups such as paediatric and geriatric patients. These essential
      characteristics are mainly satisfied by naturally occurring polymers, including
      polysaccharide based polymers which have the advantage of biocompatibility,
      biodegradability and therefore safety. This review discusses various bioadhesive
      polymers of polysaccharide origin formulated into a variety of dosage forms for
      drug delivery via the body's mucosal (moist) surfaces including ocular, oral
      (buccal and sublingual), nasal, gastrointestinal and vaginal mucosa, as well as
      moist wound sites. The anatomy and / or physiology of each site, coupled with the
      unique challenges each poses, the strategies employed for ensuring therapeutic
      efficacy, as well as the current state of the art will also be covered. 

PMID- 26290212
TI  - Use of Natural Gums and Mucilages as Pharmaceutical Excipients.
AB  - Polysaccharide rich gums and mucilages are produced by different natural sources
      such as plants, animals and microbial organisms to fulfil structural and
      physiological functions. Their diverse structural compositions with a broad range
      of physicochemical properties make them useful for inclusion in dosage forms for
      different purposes such as to improve manufacturing processes and/or to
      facilitate drug delivery. A number of natural gums and mucilages have been
      investigated for inclusion in pharmaceutical formulations for a variety of
      reasons. The search for new excipients continues to be an active topic in dosage
      form design and drug delivery research. The aim of this review article is to give
      an overview of the chemical nature of natural gums and mucilages and to discuss
      their applications in the formulation of pharmaceutical dosage forms. Special
      emphasis will be placed on the use of gums and mucilages in novel drug delivery
      systems, such as modified release dosage forms and delivery systems that target
      specific sites of delivery. 

PMID- 26290213
TI  - Examining biological vulnerability in environmental context: Parenting moderates
      effects of low resting respiratory sinus arrhythmia on adolescent depressive
      symptoms.
AB  - Polyvagal theory suggests that parasympathetic regulation of cardiac function,
      indexed by resting respiratory sinus arrhythmia (RSA), may be a marker of emotion
      regulatory capacity and associated with youth psychopathology. Contemporary
      models of psychopathology suggest that the effects of biological vulnerability
      may be moderated by developmental context. The aim of the present study was to
      examine whether parenting, particularly parental responses to youth's negative
      emotions, moderated the effects of resting RSA on depressive symptoms among early
      adolescents. We examined resting RSA, depressive symptoms, and parental responses
      to youth negative emotions among 120 adolescents aged 11-14 years (M = 12.86, SD
      = .85; 52.5% female). Resting RSA and lack of supportive parenting interacted to
      predict youth depressive symptoms, such that low resting RSA predicted more
      depressive symptoms only in the context of low levels of supportive parental
      responses to youth's negative emotions. By contrast, high resting RSA buffered
      the effects of low supportive parenting on youth depressive symptoms. These
      findings highlight the importance of understanding joint contributions of
      biological vulnerability and developmental context on youth depression outcomes.

PMID- 26290214
TI  - Attenuation of post-infarction remodeling in rats by sustained myocardial growth
      hormone administration.
AB  - Prevention of left ventricular remodeling is an important therapeutic target post
      myocardial infarction. Experimentally, treatment with growth hormone (GH) is
      beneficial, but sustained local administration has not been thoroughly
      investigated. We studied 58 rats (322 +/- 4 g). GH was administered via a
      biomaterial-scaffold, following in vitro and in vivo evaluation of degradation
      and drug-release curves. Treatment consisted of intra-myocardial injection of
      saline or alginate-hydrogel, with or without GH, 10 min after permanent coronary
      artery ligation. Echocardiographic and histologic remodeling-indices were
      examined 3 weeks post-ligation, followed by immunohistochemical evaluation of
      angiogenesis, collagen, macrophages and myofibroblasts. GH-release completed at 3
      days and alginate-degradation at ~7 days. Alginate + GH consistently improved
      left ventricular end-diastolic and end-systolic diameters, ventricular
      sphericity, wall tension index and infarct-thickness. Microvascular-density and
      myofibroblast-count in the infarct and peri-infarct areas were higher after
      alginate + GH. Macrophage-count and collagen-content did not differ between
      groups. Early, sustained GH-administration enhances angiogenesis and
      myofibroblast-activation and ameliorates post-infarction remodeling. 

PMID- 26290216
TI  - Absence of CALR mutation among a cohort of 394 unselected patients with a first
      episode of unprovoked venous thromboembolism.

PMID- 26290215
TI  - Cortical and subcortical glutathione levels in adults with autism spectrum
      disorder.
AB  - Increased oxidative stress has been postulated to contribute to the pathogenesis
      of autism spectrum disorder (ASD). However, reports of alterations in oxidation
      markers including glutathione (GSH), the major endogenous antioxidant, are
      indirect, coming from blood plasma level measurements and postmortem studies.
      Therefore we used in-vivo 3 Tesla proton magnetic resonance spectroscopy
      ([1H]MRS) to directly measure GSH concentrations in the basal ganglia (BG) and
      the dorsomedial prefrontal cortex of 21 normally intelligent adult males with ASD
      and 29 controls who did not differ in age or IQ. There was no difference in brain
      GSH between patients and controls in either brain area; neither did GSH levels
      correlate with measures of clinical severity in patients. Thus [1H]MRS measures
      of cortical and subcortical GSH are not a biomarker for ASD in intellectually
      able adult men.

PMID- 26290217
TI  - A TeGM6-4r antigen-based immunochromatographic test (ICT) for animal
      trypanosomosis.
AB  - Animal trypanosomosis is a disease that is distributed worldwide which results in
      huge economic losses due to reduced animal productivity. Endemic regions are
      often located in the countryside where laboratory diagnosis is costly or
      inaccessible. The establishment of simple, effective, and accurate field tests is
      therefore of great interest to the farming and veterinary sectors. Our study
      aimed to develop a simple, rapid, and sensitive immunochromatographic test (ICT)
      for animal trypanosomosis utilizing the recombinant tandem repeat antigen TeGM6
      4r, which is conserved amongst salivarian trypanosome species. In the specificity
      analysis, TeGM6-4r/ICT detected all of Trypanosoma evansi-positive controls from
      experimentally infected water buffaloes. As expected, uninfected controls tested
      negative. All sera samples collected from Tanzanian and Ugandan cattle that were
      Trypanosoma congolense- and/or Trypanosoma vivax-positive by microscopic
      examination of the buffy coat were found to be positive by the newly developed
      TeGM6-4r/ICT, which was comparable to results from TeGM6-4r/ELISA (kappa
      coefficient [kappa] = 0.78). TeGM6/ICT also showed substantial agreement with
      ELISA using Trypanosoma brucei brucei (kappa = 0.64) and T. congolense (kappa =
      0.72) crude antigen, suggesting the high potential of TeGM6-4r/ICT as a field
      diagnostic test, both for research purposes and on-site diagnosis of animal
      trypanosomosis. 

PMID- 26290218
TI  - Survey of Hymenolepis spp. in pet rodents in Italy.
AB  - We carried out the first survey of Hymenolepis spp. infection in pet rodents in
      Italy. Fresh fecal samples were collected from 172 pet rodents as follows: guinea
      pigs (Cavia porcellus; n = 60), squirrels (Callosciurus finlaysonii, Callosciurus
      prevosti, Tamias striatus, Tamias sibiricus, Sciurus calorinensis; n = 52),
      hamsters (Phodopus campbelli, Mesocricetus auratus; n = 30), chinchillas
      (Chinchilla lanigera; n = 13), rats (Rattus norvegicus; n = 10), and mice (Mus
      minutoides; n = 7). These animals were housed either in pet shops or in private
      houses. All fecal samples were processed using the FLOTAC pellet technique to
      assess the number of eggs per gram (EPG) of feces. Eggs of Hymenolepis nana were
      found in 24 out of 172 (13.9 %; 95 % confidence interval = 9.3-20.2 %) pet
      rodents. Of those rodents, 41.6 % (10/24) were rats (mean EPG = 55.7; range = 2
      200), 29.2 % (7/24) mice (mean EPG = 64.5; range = 32-120), 25.0 % (6/24) were
      chinchillas (mean EPG = 25.5; range = 10-50), and 4.2 % (1/24) hamsters (P.
      campbelli) (EPG = 86.0). In addition, Hymenolepis diminuta eggs were found in 2
      out of 172 (1.2 %; 95 % confidence interval = 0.2-4.6 %) rodents examined, both
      of which (100 %; 2/2) were pet squirrels (C. prevosti) (mean EPG = 10; range = 4
      16). To the authors' knowledge, this is the first report of a natural infection
      of H. diminuta in pet squirrels. 

PMID- 26290220
TI  - Cardiopulmonary Resuscitation in Small Animal Medicine: An Update.

PMID- 26290219
TI  - Nanoparticles in the fight against mosquito-borne diseases: bioactivity of
      Bruguiera cylindrica-synthesized nanoparticles against dengue virus DEN-2 (in
      vitro) and its mosquito vector Aedes aegypti (Diptera: Culicidae).
AB  - Mosquitoes are blood-feeding insects serving as the most important vectors for
      spreading human pathogens and parasites. Dengue is a viral disease mainly
      vectored through the bite of Aedes mosquitoes. Its transmission has recently
      increased in urban and semi-urban areas of tropical and subtropical regions
      worldwide, becoming a major international public health concern. There is no
      specific treatment for dengue. Its prevention and control solely depend on
      effective vector control measures. Mangrove plants have been used in Indian
      traditional medicine for a wide array of purposes. In this research, we proposed
      a method for biosynthesis of antiviral and mosquitocidal silver nanoparticles
      (AgNP) using the aqueous extract of Bruguiera cylindrica leaves. AgNP were
      characterized using a variety of biophysical analyses, including UV-visible
      spectrophotometry, Fourier-transform infrared spectroscopy, scanning electron
      microscopy, and energy-dispersive X-ray spectroscopy. Bruguiera cilyndrica
      aqueous extract and green-synthesized AgNP were tested against the primary dengue
      vector Aedes aegypti. AgNP were the most effective. LC50 values ranged from 8.93
      ppm (larva I) to 30.69 ppm (pupa). In vitro experiments showed that 30 MUg/ml of
      AgNP significantly inhibited the production of dengue viral envelope (E) protein
      in vero cells and downregulated the expression of dengue viral E gene. Concerning
      nontarget effects, we observed that the predation efficiency of Carassius auratus
      against A. aegypti was not affected by exposure at sublethal doses of AgNP.
      Predation in the control was 71.81 % (larva II) and 50.43 % (larva III), while in
      an AgNP-treated environment, predation was boosted to 90.25 and 76.81 %,
      respectively. Overall, this study highlights the concrete potential of green
      synthesized AgNP in the fight against dengue virus. Furthermore, B. cylindrica
      synthesized AgNP can be employed at low doses to reduce larval and pupal
      population of A. aegypti, without detrimental effects of predation rates of
      mosquito predators, such as C. auratus. 

PMID- 26290221
TI  - Effectiveness of locomotion training in a home visit preventive care project: one
      group pre-intervention versus post-intervention design study.
AB  - BACKGROUND: Locomotion training in a home visit-type preventive-care program has
      been reported elsewhere. However, continuation of appropriate exercises in a home
      setting is difficult, and few reports are available on locomotion training in a
      home setting. The objective of this study was to evaluate the effectiveness of
      locomotion training over 3 months in a home visit-type preventive-care program
      for improvement of motor function among elderly people. METHODS: Nine hundred and
      fifty-eight elderly people in Tendo City in Japan who were not currently
      attending any preventive-care program were invited to participate in the study,
      and 87 were enrolled. In the pre-intervention and post-intervention assessments,
      we administered an interview survey (the Kihon Checklist), the timed one-leg
      standing test with eyes open and the sit-to-stand test, at the participants'
      homes. The intervention involved one set of training exercises with the
      participants standing on each leg for 1 min and squatting five or six times. The
      participants were asked to repeat one set of the exercises three times a day at
      home. In addition, the participants were regularly asked over the telephone about
      their performance of the exercises. RESULTS: Physical strength, cognitive
      function, and total scores of the Kihon Checklist were significantly lower after
      the intervention than before. In addition, the one-leg standing test time was
      significantly longer after the intervention (mean +/- SD, 23.9 +/- 35.4) than
      before (15.7 +/- 20.5), and the sit-to-stand test time was significantly shorter
      after the intervention (13.0 +/- 6.2) than before (14.8 +/- 8.3). CONCLUSION:
      Locomotion training in a home-visit preventive-care program with telephone
      support effectively improved the motor function of elderly people who were not
      currently attending any preventive-care program organized by the long-term care
      insurance system.

PMID- 26290224
TI  - Expression of soluble adenylyl cyclase in acral melanomas.
AB  - Soluble adenylyl cyclase (sAC) regulates melanocytic cells, and is a diagnostic
      marker for pigmented skin lesions. Because only a few studies on sAC expression
      in acral melanomas have been performed, we investigated the histopathological
      significance of sAC expression in 33 cases of acral melanoma, and assessed its
      diagnostic value in distinguishing melanoma in situ (MIS, n = 17) from acral
      invasive melanomas (n = 16) and melanocytic naevi (n = 11). Acral melanomas
      exhibited more marked nuclear immunopositivity compared with acral melanocytic
      naevi. sAC expression significantly correlated with the nuclear morphology of
      melanocytes and melanoma cells, namely, hyperchromatic nuclei and prominent
      nucleoli within vesicular nuclei. sAC expression was predominantly observed in
      the hyperchromatic nuclei of MIS and the prominent nucleoli invasive melanomas,
      respectively. In vitro culture models of melanocytes and melanoma cell lines
      exhibited sAC staining patterns similar to those of acral melanomas.
      Differentiation induction showed that nuclear and nucleolar expression varied
      depending on cell morphology. sAC immunostaining may be useful for the
      differential diagnosis of acral melanocytic lesions, and sAC expressed in the
      nucleus and nucleolus might be related to cytological and nuclear changes
      associated with invasion and progression of acral melanomas. 

PMID- 26290222
TI  - Diagnosing Balamuthia mandrillaris Encephalitis With Metagenomic Deep Sequencing.
AB  - OBJECTIVE: Identification of a particular cause of meningoencephalitis can be
      challenging owing to the myriad bacteria, viruses, fungi, and parasites that can
      produce overlapping clinical phenotypes, frequently delaying diagnosis and
      therapy. Metagenomic deep sequencing (MDS) approaches to infectious disease
      diagnostics are known for their ability to identify unusual or novel viruses and
      thus are well suited for investigating possible etiologies of
      meningoencephalitis. METHODS: We present the case of a 74-year-old woman with
      endophthalmitis followed by meningoencephalitis. MDS of her cerebrospinal fluid
      (CSF) was performed to identify an infectious agent. RESULTS: Sequences aligning
      to Balamuthia mandrillaris ribosomal RNA genes were identified in the CSF by MDS.
      Polymerase chain reaction subsequently confirmed the presence of B. mandrillaris
      in CSF, brain tissue, and vitreous fluid from the patient's infected eye. B.
      mandrillaris serology and immunohistochemistry for free-living amoebas on the
      brain biopsy tissue were positive. INTERPRETATION: The diagnosis was made using
      MDS after the patient had been hospitalized for several weeks and subjected to
      costly and invasive testing. MDS is a powerful diagnostic tool with the potential
      for rapid and unbiased pathogen identification leading to early therapeutic
      targeting.

PMID- 26290225
TI  - Synthesis of the Proposed Structure of Damaurone D and Evaluation of Its Anti
      inflammatory Activity.
AB  - Concise and efficient synthesis of the proposed structure of damaurone D is
      accomplished in five steps without protection-deprotection operations. The key
      feature of our synthesis includes a versatile aldol reaction of the
      benzofuranone, provided by selective alpha-halogenation and intramolecular O
      alkylation. However, the H- and C-NMR spectral data of the synthesized damaurone
      D did not agree with previous reports. The structure of the synthesized damaurone
      D was confirmed using combined two dimensional (2D)-NMR analysis, including
      heteronuclear single quantum coherence (HSQC), heteronuclear multiple bond
      connectivity (HMBC), and nuclear Overhauser effect spectroscopy (NOESY). The
      synthesized damaurone D was found to exhibit potent anti-inflammatory activity in
      murine macrophage RAW264.7 cells, which was demonstrated by the findings that
      damaurone D treatment in cells resulted in the inhibition of lipopolysaccharide
      (LPS)-stimulated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX
      2) expression and nitrite production. 

PMID- 26290226
TI  - Do SNARE Protein Isoforms Determine Fusion Pore Characteristics?

PMID- 26290228
TI  - Sox2 Sustains Recruitment of Oligodendrocyte Progenitor Cells following CNS
      Demyelination and Primes Them for Differentiation during Remyelination.
AB  - The Sox family of transcription factors have been widely studied in the context
      of oligodendrocyte development. However, comparatively little is known about the
      role of Sox2, especially during CNS remyelination. Here we show that the
      expression of Sox2 occurs in oligodendrocyte progenitor cells (OPCs) in rodent
      models during myelination and in activated adult OPCs responding to
      demyelination, and is also detected in multiple sclerosis lesions. In normal
      adult white matter of both mice and rats, it is neither expressed by adult OPCs
      nor by oligodendrocytes (although it is expressed by a subpopulation of adult
      astrocytes). Overexpression of Sox2 in rat OPCs in vitro maintains the cells in a
      proliferative state and inhibits differentiation, while Sox2 knockout results in
      decreased OPC proliferation and survival, suggesting that Sox2 contributes to the
      expansion of OPCs during the recruitment phase of remyelination. Loss of function
      in cultured mouse OPCs also results in an impaired ability to undergo normal
      differentiation in response to differentiation signals, suggesting that Sox2
      expression in activated OPCs also primes these cells to eventually undergo
      differentiation. In vivo studies on remyelination following experimental toxin
      induced demyelination in mice with inducible loss of Sox2 revealed impaired
      remyelination, which was largely due to a profound attenuation of OPC recruitment
      and likely also due to impaired differentiation. Our results reveal a key role of
      Sox2 expression in OPCs responding to demyelination, enabling them to effectively
      contribute to remyelination. SIGNIFICANCE STATEMENT: Understanding the mechanisms
      of CNS remyelination is central to developing effective means by which this
      process can be therapeutically enhanced in chronic demyelinating diseases such as
      multiple sclerosis. In this study, we describe the role of Sox2, a transcription
      factor widely implicated in stem cell biology, in CNS myelination and
      remyelination. We show how Sox2 is expressed in oligodendrocyte progenitor cells
      (OPCs) preparing to undergo differentiation, allowing them to undergo
      proliferation and priming them for subsequent differentiation. Although Sox2 is
      unlikely to be a direct therapeutic target, these data nevertheless provide more
      information on how OPC differentiation is controlled and therefore enriches our
      understanding of this important CNS regenerative process.

PMID- 26290227
TI  - Retinoic Acid-Mediated Regulation of GLI3 Enables Efficient Motoneuron Derivation
      from Human ESCs in the Absence of Extrinsic SHH Activation.
AB  - The derivation of somatic motoneurons (MNs) from ES cells (ESCs) after exposure
      to sonic hedgehog (SHH) and retinoic acid (RA) is one of the best defined,
      directed differentiation strategies to specify fate in pluripotent lineages. In
      mouse ESCs, MN yield is particularly high after RA + SHH treatment, whereas human
      ESC (hESC) protocols have been generally less efficient. In an effort to optimize
      yield, we observe that functional MNs can be derived from hESCs at high
      efficiencies if treated with patterning molecules at very early differentiation
      steps before neural induction. Remarkably, under these conditions, equal numbers
      of human MNs were obtained in the presence or absence of SHH exposure. Using
      pharmacological and genetic strategies, we demonstrate that early RA treatment
      directs MN differentiation independently of extrinsic SHH activation by
      suppressing the induction of GLI3. We further demonstrate that neural induction
      triggers a switch from a poised to an active chromatin state at GLI3. Early RA
      treatment prevents this switch by direct binding of the RA receptor at the GLI3
      promoter. Furthermore, GLI3 knock-out hESCs can bypass the requirement for early
      RA patterning to yield MNs efficiently. Our data demonstrate that RA-mediated
      suppression of GLI3 is sufficient to generate MNs in an SHH-independent manner
      and that temporal changes in exposure to patterning factors such as RA affect
      chromatin state and competency of hESC-derived lineages to adopt specific
      neuronal fates. Finally, our work presents a streamlined platform for the highly
      efficient derivation of human MNs from ESCs and induced pluripotent stem cells.
      SIGNIFICANCE STATEMENT: Our study presents a rapid and efficient protocol to
      generate human motoneurons from embryonic and induced pluripotent stem cells.
      Surprisingly, and in contrast to previous work, motoneurons are generated in the
      presence of retinoic acid but in the absence of factors that activate sonic
      hedgehog signaling. We show that early exposure to retinoic acid modulates the
      chromatin state of cells to be permissive for motoneuron generation and directly
      suppresses the induction of GLI3, a negative regulator of SHH signaling.
      Therefore, our data point to a novel mechanism by which retinoic acid exposure
      can bypass the requirement for extrinsic SHH treatment during motoneuron
      induction.

PMID- 26290229
TI  - Blocking IGF Signaling in Adult Neurons Alleviates Alzheimer's Disease Pathology
      through Amyloid-beta Clearance.
AB  - Alzheimer's disease (AD) is a frequent and irreversible age-related
      neurodegeneration without efficient treatment. Experimental AD in mice responds
      positively to decreased insulin-like growth factor I (IGF-I) signaling, a pathway
      also implicated in aging. Here we aimed to protect the aging brain from
      devastating amyloid pathology by making specifically adult neurons resistant to
      IGF signaling. To achieve that, we knocked out neuronal IGF-1R during adulthood
      in APP/PS1 mice. We found that mutants exhibited improved spatial memory and
      reduced anxiety. Mutant brains displayed fewer amyloid plaques, less amyloid-beta
      (Abeta), and diminished neuroinflammation. Surprisingly, adult neurons undergoing
      IGF-1R knock-out reduced their apical soma and developed leaner dendrites,
      indicative of remarkable structural plasticity entailing condensed forebrain
      neuroarchitecture. Neurons lacking IGF-1R in AD showed less accumulation of Abeta
      containing autophagic vacuoles. At the same time, plasma Abeta levels were
      increased. Our data indicate that neuronal IGF-1R ablation, via preserved
      autophagic compartment and enhanced systemic elimination, offers lifelong
      protection from AD pathology by clearing toxic Abeta. Neuronal IGF-1R, and
      possibly other cell size-controlling pathways are promising targets for AD
      treatment. SIGNIFICANCE STATEMENT: We found compelling evidence in vivo that
      Alzheimer's disease (AD) progression is significantly delayed when insulin-like
      growth factor (IGF) signaling is blocked in adult neurons. To show that, we built
      a novel mouse model, combining inducible neuron-specific IGF-1R knock-out with AD
      transgenics. Analysis of the experimental AD phenotype revealed less abundant
      amyloid-beta (Abeta) peptides, fewer plaques, and diminished neuroinflammation in
      mutants with inactivated IGF signaling, together with clearly preserved
      behavioral and memory performances. We present for the first time evidence that
      IGF signaling has profound effects on neuronal proteostasis and maintenance of
      cell morphology in vivo. Our results indicate in a model highly pertinent to
      translational research that neuronal IGF resistance may represent a
      pathophysiologically relevant mechanism of the brain for preventing Abeta
      accumulation.

PMID- 26290230
TI  - Ubiquitin-Synaptobrevin Fusion Protein Causes Degeneration of Presynaptic Motor
      Terminals in Mice.
AB  - Protein aggregates containing ubiquitin (Ub) are commonly observed in
      neurodegenerative disorders, implicating the involvement of the ubiquitin
      proteasome system (UPS) in their pathogenesis. Here, we aimed to generate a mouse
      model for monitoring UPS function using a green fluorescent protein (GFP)-based
      substrate that carries a "noncleavable" N-terminal ubiquitin moiety (Ub(G76V)).
      We engineered transgenic mice expressing a fusion protein, consisting of the
      following: (1) Ub(G76V), GFP, and a synaptic vesicle protein synaptobrevin-2
      (Ub(G76V)-GFP-Syb2); (2) GFP-Syb2; or (3) Ub(G76V)-GFP-Syntaxin1, all under the
      control of a neuron-specific Thy-1 promoter. As expected, Ub(G76V)-GFP-Syb2, GFP
      Syb2, and Ub(G76V)-GFP-Sytaxin1 were highly expressed in neurons, such as
      motoneurons and motor nerve terminals of the neuromuscular junction (NMJ).
      Surprisingly, Ub(G76V)-GFP-Syb2 mice developed progressive adult-onset
      degeneration of motor nerve terminals, whereas GFP-Syb2 and Ub(G76V)-GFP
      Syntaxin1 mice were normal. The degeneration of nerve terminals in Ub(G76V)-GFP
      Syb2 mice was preceded by a progressive impairment of synaptic transmission at
      the NMJs. Biochemical analyses demonstrated that Ub(G76V)-GFP-Syb2 interacted
      with SNAP-25 and Syntaxin1, the SNARE partners of synaptobrevin. Ultrastructural
      analyses revealed a marked reduction in synaptic vesicle density, accompanying an
      accumulation of tubulovesicular structures at presynaptic nerve terminals. These
      morphological defects were largely restricted to motor nerve terminals, as the
      ultrastructure of motoneuron somata appeared to be normal at the stages when
      synaptic nerve terminals degenerated. Furthermore, synaptic vesicle endocytosis
      and membrane trafficking were impaired in Ub(G76V)-GFP-Syb2 mice. These findings
      indicate that Ub(G76V)-GFP-Syb2 may compete with endogenous synaptobrevin, acting
      as a gain-of-function mutation that impedes SNARE function, resulting in the
      depletion of synaptic vesicles and degeneration of the nerve terminals.
      SIGNIFICANCE STATEMENT: Degeneration of motor nerve terminals occurs in
      amyotrophic lateral sclerosis (ALS) patients as well as in mouse models of ALS,
      leading to progressive paralysis. What causes a motor nerve terminal to
      degenerate remains unknown. Here we report on transgenic mice expressing a
      ubiquitinated synaptic vesicle protein (Ub(G76V)-GFP-Syb2) that develop
      progressive degeneration of motor nerve terminals. These mice may serve as a
      model for further elucidating the underlying cellular and molecular mechanisms of
      presynaptic nerve terminal degeneration.

PMID- 26290231
TI  - Cortical Coupling Reflects Bayesian Belief Updating in the Deployment of Spatial
      Attention.
AB  - The deployment of visuospatial attention and the programming of saccades are
      governed by the inferred likelihood of events. In the present study, we combined
      computational modeling of psychophysical data with fMRI to characterize the
      computational and neural mechanisms underlying this flexible attentional control.
      Sixteen healthy human subjects performed a modified version of Posner's location
      cueing paradigm in which the percentage of cue validity varied in time and the
      targets required saccadic responses. Trialwise estimates of the certainty
      (precision) of the prediction that the target would appear at the cued location
      were derived from a hierarchical Bayesian model fitted to individual trialwise
      saccadic response speeds. Trial-specific model parameters then entered analyses
      of fMRI data as parametric regressors. Moreover, dynamic causal modeling (DCM)
      was performed to identify the most likely functional architecture of the
      attentional reorienting network and its modulation by (Bayes-optimal) precision
      dependent attention. While the frontal eye fields (FEFs), intraparietal sulcus,
      and temporoparietal junction (TPJ) of both hemispheres showed higher activity on
      invalid relative to valid trials, reorienting responses in right FEF, TPJ, and
      the putamen were significantly modulated by precision-dependent attention. Our
      DCM results suggested that the precision of predictability underlies the
      attentional modulation of the coupling of TPJ with FEF and the putamen. Our
      results shed new light on the computational architecture and neuronal network
      dynamics underlying the context-sensitive deployment of visuospatial attention.
      SIGNIFICANCE STATEMENT: Spatial attention and its neural correlates in the human
      brain have been studied extensively with the help of fMRI and cueing paradigms in
      which the location of targets is pre-cued on a trial-by-trial basis. One aspect
      that has so far been neglected concerns the question of how the brain forms
      attentional expectancies when no a priori probability information is available
      but needs to be inferred from observations. This study elucidates the
      computational and neural mechanisms under which probabilistic inference governs
      attentional deployment. Our results show that Bayesian belief updating explains
      changes in cortical connectivity; in that directional influences from the
      temporoparietal junction on the frontal eye fields and the putamen were modulated
      by (Bayes-optimal) updates.

PMID- 26290233
TI  - Position and Identity Information Available in fMRI Patterns of Activity in Human
      Visual Cortex.
AB  - Parietal cortex is often implicated in visual processing of actions. Action
      understanding is essentially abstract, specific to the type or goal of action,
      but greatly independent of variations in the perceived position of the action. If
      certain parietal regions are involved in action understanding, then we expect
      them to show these generalization and selectivity properties. However, additional
      functions of parietal cortex, such as self-action control, may impose other
      demands by requiring an accurate representation of the location of graspable
      objects. Therefore, the dimensions along which responses are modulated may
      indicate the functional role of specific parietal regions. Here, we studied the
      degree of position invariance and hand/object specificity during viewing of tool
      grasping actions. To that end, we characterize the information available about
      location, hand, and tool identity in the patterns of fMRI activation in various
      cortical areas: early visual cortex, posterior intraparietal sulcus, anterior
      superior parietal lobule, and the ventral object-specific lateral occipital
      complex. Our results suggest a gradient within the human dorsal stream: along the
      posterior-anterior axis, position information is gradually lost, whereas hand and
      tool identity information is enhanced. This may reflect a gradual transformation
      of visual input from an initial retinotopic representation in early visual areas
      to an abstract, position-invariant representation of viewed action in anterior
      parietal cortex. SIGNIFICANCE STATEMENT: Since the seminal study of Goodale and
      Milner (1992), there is general agreement that visual processing is largely
      divided between a ventral and dorsal stream specializing in object recognition
      and vision for action, respectively. Here, we address the specific representation
      of viewed actions. Specifically, we study the degree of position invariance and
      hand/object manipulation specificity in the human visual pathways, characterizing
      the information available in patterns of fMRI activation during viewing of object
      grasping videos, which appeared in different retinal locations. We find
      converging evidence for a gradient within the dorsal stream: along the posterior
      anterior axis, position information is gradually lost, whereas hand and action
      identity information is enhanced, leading to an abstract, position-invariant
      representation of viewed action in the anterior parietal cortex.

PMID- 26290232
TI  - Hepatocyte Growth Factor and MET Support Mouse Enteric Nervous System
      Development, the Peristaltic Response, and Intestinal Epithelial Proliferation in
      Response to Injury.
AB  - Factors providing trophic support to diverse enteric neuron subtypes remain
      poorly understood. We tested the hypothesis that hepatocyte growth factor (HGF)
      and the HGF receptor MET might support some types of enteric neurons. HGF and MET
      are expressed in fetal and adult enteric nervous system. In vitro, HGF increased
      enteric neuron differentiation and neurite length, but only if vanishingly small
      amounts (1 pg/ml) of glial cell line-derived neurotrophic factor were included in
      culture media. HGF effects were blocked by phosphatidylinositol-3 kinase
      inhibitor and by MET-blocking antibody. Both of these inhibitors and MEK
      inhibition reduced neurite length. In adult mice, MET was restricted to a subset
      of calcitonin gene-related peptide-immunoreactive (IR) myenteric plexus neurons
      thought to be intrinsic primary afferent neurons (IPANs). Conditional MET kinase
      domain inactivation (Met(fl/fl); Wnt1Cre+) caused a dramatic loss of myenteric
      plexus MET-IR neurites and 1-1'-dioctodecyl-3,3,3',3'-tetramethylindocarbocyamine
      perchlorate (DiI) labeling suggested reduced MET-IR neurite length. In vitro,
      Met(fl/fl); Wnt1Cre+ mouse bowel had markedly reduced peristalsis in response to
      mucosal deformation, but normal response to radial muscle stretch. However, whole
      bowel transit, small-bowel transit, and colonic-bead expulsion were normal in
      Met(fl/fl); Wnt1Cre+ mice. Finally, Met(fl/fl); Wnt1Cre+ mice had more bowel
      injury and reduced epithelial cell proliferation compared with WT animals after
      dextran sodium sulfate treatment. These results suggest that HGF/MET signaling is
      important for development and function of a subset IPANs and that these cells
      regulate intestinal motility and epithelial cell proliferation in response to
      bowel injury. SIGNIFICANCE STATEMENT: The enteric nervous system has many
      neuronal subtypes that coordinate and control intestinal activity. Trophic
      factors that support these neuron types and enhance neurite growth after fetal
      development are not well understood. We show that a subset of adult calcitonin
      gene-related peptide (CGRP)-expressing myenteric neurons produce MET, the
      receptor for hepatocyte growth factor, and that loss of MET activity affects
      peristalsis in response to mucosal stroking, reduces MET-immunoreactive neurites,
      and increases susceptibility to dextran sodium sulfate-induced bowel injury.
      These observations may be relevant for understanding and treating intestinal
      motility disorders and also suggest that enhancing the activity of MET-expressing
      CGRP neurons might be a useful strategy to reduce bowel inflammation.

PMID- 26290234
TI  - Differential Dopamine Release Dynamics in the Nucleus Accumbens Core and Shell
      Reveal Complementary Signals for Error Prediction and Incentive Motivation.
AB  - Mesolimbic dopamine (DA) is phasically released during appetitive behaviors,
      though there is substantive disagreement about the specific purpose of these DA
      signals. For example, prediction error (PE) models suggest a role of learning,
      while incentive salience (IS) models argue that the DA signal imbues stimuli with
      value and thereby stimulates motivated behavior. However, within the nucleus
      accumbens (NAc) patterns of DA release can strikingly differ between subregions,
      and as such, it is possible that these patterns differentially contribute to
      aspects of PE and IS. To assess this, we measured DA release in subregions of the
      NAc during a behavioral task that spatiotemporally separated sequential goal
      directed stimuli. Electrochemical methods were used to measure subsecond NAc
      dopamine release in the core and shell during a well learned instrumental chain
      schedule in which rats were trained to press one lever (seeking; SL) to gain
      access to a second lever (taking; TL) linked with food delivery, and again during
      extinction. In the core, phasic DA release was greatest following initial SL
      presentation, but minimal for the subsequent TL and reward events. In contrast,
      phasic shell DA showed robust release at all task events. Signaling decreased
      between the beginning and end of sessions in the shell, but not core. During
      extinction, peak DA release in the core showed a graded decrease for the SL and
      pauses in release during omitted expected rewards, whereas shell DA release
      decreased predominantly during the TL. These release dynamics suggest parallel DA
      signals capable of supporting distinct theories of appetitive behavior.
      SIGNIFICANCE STATEMENT: Dopamine signaling in the brain is important for a
      variety of cognitive functions, such as learning and motivation. Typically, it is
      assumed that a single dopamine signal is sufficient to support these cognitive
      functions, though competing theories disagree on how dopamine contributes to
      reward-based behaviors. Here, we have found that real-time dopamine release
      within the nucleus accumbens (a primary target of midbrain dopamine neurons)
      strikingly varies between core and shell subregions. In the core, dopamine
      dynamics are consistent with learning-based theories (such as reward prediction
      error) whereas in the shell, dopamine is consistent with motivation-based
      theories (e.g., incentive salience). These findings demonstrate that dopamine
      plays multiple and complementary roles based on discrete circuits that help
      animals optimize rewarding behaviors.

PMID- 26290235
TI  - The Brain Correlates of Laugh and Cataplexy in Childhood Narcolepsy.
AB  - The brain suprapontine mechanisms associated with human cataplexy have not been
      clarified. Animal data suggest that the amygdala and the ventromedial prefrontal
      cortex are key regions in promoting emotion-induced cataplectic attacks. Twenty
      one drug-naive children/adolescent (13 males, mean age 11 years) with recent
      onset of narcolepsy type 1 (NT1) were studied with fMRI while viewing funny
      videos using a "naturalistic" paradigm. fMRI data were acquired synchronously
      with EEG, mylohyoid muscle activity, and the video of the patient's face. Whole
      brain hemodynamic correlates of (1) a sign of fun and amusement (laughter) and of
      (2) cataplexy were analyzed and compared. Correlations analyses between these
      contrasts and disease-related variables and behavioral findings were performed.
      SIGNIFICANCE STATEMENT: In this study we reported for the first time in humans
      the brain structures whose neural activity is specifically and consistently
      associated with emotion-induced cataplexy. To reach this goal drug-naive children
      and adolescents with recent onset narcolepsy type 1 were investigated. In
      narcolepsy caused by hypocretin/orexin deficiency, cataplexy is associated with a
      marked increase in neural activity in the amygdala, the nucleus accumbens, and
      the ventromedial prefrontal cortex, which represent suprapontine centers that
      physiologically process emotions and reward. These findings confirm recent data
      obtained in the hypocretin knock-out mice and suggest that the absence of
      hypothalamic hypocretin control on mesolimbic reward centers is crucial in
      determining cataplexy induced by emotions. Emotion-induced laughter occurred in
      16 patients, and of these 10 showed cataplexy for a total of 77 events (mean
      duration = 4.4 s). Cataplexy was marked by brief losses of mylohyoid muscle tone
      and by the observation of episodes of facial hypotonia, jaw drop, and ptosis.
      During laughter (without cataplexy) an increased hemodynamic response occurred in
      a bilateral network involving the motor/premotor cortex and anterior cingulate
      gyrus. During cataplexy, suprapontine BOLD signal increase was present in the
      amygdala, frontal operculum-anterior insular cortex, ventromedial prefrontal
      cortex, and the nucleus accumbens; BOLD signal increases were also observed at
      locus ceruleus and in anteromedial pons. The comparison of cataplexy versus laugh
      episodes revealed the involvement of a corticolimbic network that processes
      reward and emotion encompassing the anterior insular cortex, the nucleus
      accumbens, and the amygdala.

PMID- 26290236
TI  - Is a Responsive Default Mode Network Required for Successful Working Memory Task
      Performance?
AB  - In studies of cognitive processing using tasks with externally directed
      attention, regions showing increased (external-task-positive) and decreased or
      "negative" [default-mode network (DMN)] fMRI responses during task performance
      are dynamically responsive to increasing task difficulty. Responsiveness
      (modulation of fMRI signal by increasing load) has been linked directly to
      successful cognitive task performance in external-task-positive regions but not
      in DMN regions. To investigate whether a responsive DMN is required for
      successful cognitive performance, we compared healthy human subjects (n = 23)
      with individuals shown to have decreased DMN engagement (chronic pain patients, n
      = 28). Subjects performed a multilevel working-memory task (N-back) during fMRI.
      If a responsive DMN is required for successful performance, patients having
      reduced DMN responsiveness should show worsened performance; if performance is
      not reduced, their brains should show compensatory activation in external-task
      positive regions or elsewhere. All subjects showed decreased accuracy and
      increased reaction times with increasing task level, with no significant group
      differences on either measure at any level. Patients had significantly reduced
      negative fMRI response (deactivation) of DMN regions (posterior
      cingulate/precuneus, medial prefrontal cortex). Controls showed expected
      modulation of DMN deactivation with increasing task difficulty. Patients showed
      significantly reduced modulation of DMN deactivation by task difficulty, despite
      their successful task performance. We found no evidence of compensatory neural
      recruitment in external-task-positive regions or elsewhere. Individual
      responsiveness of the external-task-positive ventrolateral prefrontal cortex, but
      not of DMN regions, correlated with task accuracy. These findings suggest that a
      responsive DMN may not be required for successful cognitive performance; a
      responsive external-task-positive network may be sufficient. SIGNIFICANCE
      STATEMENT: We studied the relationship between responsiveness of the brain to
      increasing task demand and successful cognitive performance, using chronic pain
      patients as a probe. fMRI working memory studies show that two main cognitive
      networks ["external-task positive" and "default-mode network" (DMN)] are
      responsive to increasing task difficulty. The responsiveness of both of these
      brain networks is suggested to be required for successful task performance. The
      responsiveness of external-task-positive regions has been linked directly to
      successful cognitive task performance, as we also show here. However, pain
      patients show decreased engagement and responsiveness of the DMN but can perform
      a working memory task as well as healthy subjects, without demonstrable
      compensatory neural recruitment. Therefore, a responsive DMN might not be needed
      for successful cognitive performance.

PMID- 26290237
TI  - Synaptic Depression Influences Inspiratory-Expiratory Phase Transition in Dbx1
      Interneurons of the preBotzinger Complex in Neonatal Mice.
AB  - The brainstem preBotzinger complex (preBotC) generates the rhythm underlying
      inspiratory breathing movements and its core interneurons are derived from Dbx1
      expressing precursors. Recurrent synaptic excitation is required to initiate
      inspiratory bursts, but whether excitatory synaptic mechanisms also contribute to
      inspiratory-expiratory phase transition is unknown. Here, we examined the role of
      short-term synaptic depression using a rhythmically active neonatal mouse
      brainstem slice preparation. We show that afferent axonal projections to Dbx1
      preBotC neurons undergo activity-dependent depression and we identify a
      refractory period (~2 s) after endogenous inspiratory bursts that precludes light
      evoked bursts in channelrhodopsin-expressing Dbx1 preBotC neurons. We demonstrate
      that the duration of the refractory period-but neither the cycle period nor the
      magnitude of endogenous inspiratory bursts-is sensitive to changes in
      extracellular Ca(2+). Further, we show that postsynaptic factors are unlikely to
      explain the refractory period or its modulation by Ca(2+). Our findings are
      consistent with the hypothesis that short-term synaptic depression in Dbx1
      preBotC neurons influences the inspiratory-expiratory phase transition during
      respiratory rhythmogenesis. SIGNIFICANCE STATEMENT: Theories of breathing's
      neural origins have heretofore focused on intrinsically bursting "pacemaker"
      cells operating in conjunction with synaptic inhibition for phase transition and
      cycle timing. However, contemporary studies falsify an obligatory role for
      pacemaker-like neurons and synaptic inhibition, giving credence to burst
      generating mechanisms based on recurrent excitation among glutamatergic
      interneurons of the respiratory kernel. Here, we investigated the role of short
      term synaptic depression in inspiratory-expiratory phase transition. Until now,
      this role remained an untested prediction of mathematical models. The present
      data emphasize that synaptic properties of excitatory interneurons of the
      respiratory rhythmogenic kernel, derived from Dbx1-expressing precursors, may
      provide the core logic underlying the rhythm for breathing.

PMID- 26290238
TI  - Ketamine-Induced Changes in the Signal and Noise of Rule Representation in
      Working Memory by Lateral Prefrontal Neurons.
AB  - Working memory dysfunction is an especially debilitating symptom in
      schizophrenia. The NMDA antagonist ketamine has been successfully used to model
      working memory deficits in both rodents and nonhuman primates, but how it affects
      the strength and the consistency of working memory representations remains
      unclear. Here we recorded single-neuron activity in the lateral prefrontal cortex
      of macaque monkeys before and after the administration of subanesthetic doses of
      ketamine in a rule-based working memory task. The rule was instructed with a
      color cue before each delay period and dictated the correct prosaccadic or
      antisaccadic response to a peripheral stimulus appearing after the delay. We
      found that acute ketamine injections both weakened the rule signal across all
      delay periods and amplified the trial-to-trial variance in neural activities
      (i.e., noise), both within individual neurons and at the ensemble level,
      resulting in impaired performance. In the minority of postinjection trials when
      the animals responded correctly, the preservation of the signal strength during
      the delay periods was predictive of their subsequent success. Our findings
      suggest that NMDA receptor function may be critical for establishing the optimal
      signal-to-noise ratio in information representation by ensembles of prefrontal
      cortex neurons. SIGNIFICANCE STATEMENT: In schizophrenia patients, working memory
      deficit is highly debilitating and currently without any efficacious treatment.
      An improved understanding of the pathophysiology of this symptom may provide
      critical information to treatment development. The NMDA antagonist ketamine, when
      injected at a subanesthetic dose, produces working memory deficit and other
      schizophrenia-like symptoms in humans and other animals. Here we investigated the
      effects of ketamine on the representation of abstract rules by prefrontal
      neurons, while macaque monkeys held the rules in working memory before responding
      accordingly. We found that ketamine weakened the signal-to-noise ratio in rule
      representation by simultaneously weakening the signal and augmenting noise. Both
      processes may be relevant in an effective therapy for working memory impairment
      in schizophrenia.

PMID- 26290239
TI  - Integration of New Information with Active Memory Accounts for Retrograde
      Amnesia: A Challenge to the Consolidation/Reconsolidation Hypothesis?
AB  - Active (new and reactivated) memories are considered to be labile and sensitive
      to treatments disrupting the time-dependent consolidation/reconsolidation
      processes required for their stabilization. Active memories also allow the
      integration of new information for updating memories. Here, we investigate the
      possibility that, when active, the internal state provided by amnesic treatments
      is represented and integrated within the initial memory and that amnesia results
      from the absence of this state at testing. We showed in rats that the amnesia
      resulting from systemic, intracerebroventricular and intrahippocampal injections
      of the protein synthesis inhibitor cycloheximide, administered after inhibitory
      avoidance training or reactivation, can be reversed by a reminder, including re
      administration of the same drug. Similar results were obtained with lithium
      chloride (LiCl), which does not affect protein synthesis, when delivered
      systemically after training or reactivation. However, LiCl can induce memory
      given that a conditioned taste aversion was obtained for a novel taste, presented
      just before conditioning or reactivation. These results indicate that memories
      can be established and maintained without de novo protein synthesis and that
      experimental amnesia may not result from a disruption of memory
      consolidation/reconsolidation. The findings more likely support the integration
      hypothesis: posttraining/postreactivation treatments induce an internal state,
      which becomes encoded with the memory, and should be present at the time of
      testing to ensure a successful retrieval. This integration concept includes most
      of the previous explanations of memory recovery after retrograde amnesia and
      critically challenges the traditional memory consolidation/reconsolidation
      hypothesis, providing a more dynamic and flexible view of memory. SIGNIFICANCE
      STATEMENT: This study provides evidence challenging the traditional
      consolidation/reconsolidation hypotheses that have dominated the literature over
      the past 50 years. Based on amnesia studies, that hypothesis states that active
      (i.e., new and reactivated) memories are similarly labile and (re)established in
      a time-dependent manner within the brain through processes that require de novo
      protein synthesis. Our data show that new/reactivated memories can be formed
      without protein synthesis and that amnesia can be induced by drugs that do not
      affect protein synthesis. We propose that amnesia results from memory integration
      of the internal state produced by the drug that is subsequently necessary for
      retrieval of the memory. This interpretation gives a dynamic view of memory,
      rapidly stored and easily updated when active.

PMID- 26290241
TI  - Direction-Specific Adaptation in Neuronal and Behavioral Responses of an Insect
      Mechanosensory System.
AB  - Stimulus-specific adaptation (SSA) is considered to be the neural underpinning of
      habituation to frequent stimuli and novelty detection. However, neither the
      cellular mechanism underlying SSA nor the link between SSA-like neuronal
      plasticity and behavioral modulation is well understood. The wind-detection
      system in crickets is one of the best models for investigating the neural basis
      of SSA. We found that crickets exhibit stimulus-direction-specific adaptation in
      wind-elicited avoidance behavior. Repetitive air currents inducing this
      behavioral adaptation reduced firings to the stimulus and the amplitude of
      excitatory synaptic potentials in wind-sensitive giant interneurons (GIs) related
      to the avoidance behavior. Injection of a Ca(2+) chelator into GIs diminished
      both the attenuation of firings and the synaptic depression induced by the
      repetitive stimulation, suggesting that adaptation of GIs induced by this
      stimulation results in Ca(2+)-mediated modulation of postsynaptic responses,
      including postsynaptic short-term depression. Some types of GIs showed specific
      adaptation to the direction of repetitive stimuli, resulting in an alteration of
      their directional tuning curves. The types of GIs for which directional tuning
      was altered displayed heterogeneous direction selectivity in their Ca(2+)
      dynamics that was restricted to a specific area of dendrites. In contrast, other
      types of GIs with constant directionality exhibited direction-independent global
      Ca(2+) elevation throughout the dendritic arbor. These results suggest that
      depression induced by local Ca(2+) accumulation at repetitively activated
      synapses of key neurons underlies direction-specific behavioral adaptation. This
      input-selective depression mediated by heterogeneous Ca(2+) dynamics could confer
      the ability to detect novelty at the earliest stages of sensory processing in
      crickets. SIGNIFICANCE STATEMENT: Stimulus-specific adaptation (SSA) is
      considered to be the neural underpinning of habituation and novelty detection. We
      found that crickets exhibit stimulus-direction-specific adaptation in wind
      elicited avoidance behavior. Repetitive air currents inducing this behavioral
      adaptation altered the directional selectivity of wind-sensitive giant
      interneurons (GIs) via direction-specific adaptation mediated by dendritic Ca(2+)
      elevation. The GIs for which directional tuning was altered displayed
      heterogeneous direction selectivity in their Ca(2+) dynamics and the transient
      increase in Ca(2+) evoked by the repeated puffs was restricted to a specific area
      of dendrites. These results suggest that depression induced by local Ca(2+)
      accumulation at repetitively activated synapses of key neurons underlies
      direction-specific behavioral adaptation. Our findings elucidate the subcellular
      mechanism underlying SSA-like neuronal plasticity related to behavioral
      adaptation.

PMID- 26290240
TI  - Alcohol Elicits Functional and Structural Plasticity Selectively in Dopamine D1
      Receptor-Expressing Neurons of the Dorsomedial Striatum.
AB  - Addiction is thought to be a maladaptive form of learning and memory caused by
      drug-evoked aberrant synaptic plasticity. We previously showed that alcohol
      facilitates synaptic plasticity in the dorsomedial striatum (DMS), a brain region
      that drives goal-directed behaviors. The majority of DMS cells are medium spiny
      neurons (MSNs) that express dopamine D1 receptors (D1Rs) or D2 receptors (D2Rs),
      which drive "Go" or "No-Go" behaviors, respectively. Here, we report that alcohol
      induces cell type-specific synaptic and structural plasticity in the DMS. Using
      mice that express a fluorescence marker to visualize D1R or D2R MSNs, we show
      that repeated cycles of systemic administration of alcohol or alcohol consumption
      induces a long-lasting increase in AMPAR activity specifically in DMS D1R but not
      in D2R MSNs. Importantly, we report that alcohol consumption increases the
      complexity of dendritic branching and the density of mature mushroom-shaped
      spines selectively in DMS D1R MSNs. Finally, we found that blockade of D1R but
      not D2R activity in the DMS attenuates alcohol consumption. Together, these data
      suggest that alcohol intake produces profound functional and structural
      plasticity events in a subpopulation of neurons in the DMS that control
      reinforcement-related learning. SIGNIFICANCE STATEMENT: Alcohol addiction is
      considered maladaptive learning and memory processes. Here we unraveled a long
      lasting cellular mechanism that may contribute to the memory of alcohol-seeking
      behaviors. Specifically, we found that alcohol consumption produces a long
      lasting enhancement of channel activity and persistent alterations of neuronal
      morphology in a part of the brain (DMS) that controls alcohol-drinking behaviors.
      Furthermore, we show that these alterations occur only in a subpopulation of
      neurons that positively control reward and reinforcement of drugs of abuse.
      Finally, we report that blocking the activity of this neuronal population reduces
      alcohol intake. As such synaptic and structural changes are the cellular
      hallmarks of learning and memory, and these neuroadaptations may drive the
      development of pathological heavy alcohol consumption.

PMID- 26290243
TI  - Novel Behavioral Paradigm Reveals Lower Temporal Limits on Mouse Olfactory
      Decisions.
AB  - Temporal limits on perceptual decisions set strict boundaries on the possible
      underlying neural computations. How odor information is encoded in the olfactory
      system is still poorly understood. Here, we sought to define the limit on the
      speed of olfactory processing. To achieve this, we trained mice to discriminate
      different odor concentrations in a novel behavioral setup with precise odor
      delivery synchronized to the sniffing cycle. Mice reported their choice by moving
      a horizontal treadmill with their front limbs. We found that mice reported
      discriminations of 75% accuracy in 70-90 ms after odor inhalation. For a low
      concentration and nontrigeminal odorant, this time was 90-140 ms, showing that
      mice process odor information rapidly even in the absence of trigeminal
      stimulation. These response times establish, after accounting for odor
      transduction and motor delays, that olfactory processing can take tens of
      milliseconds. This study puts a strong limit on the underlying neural
      computations and suggests that the action potentials forming the neural basis for
      these decisions are fired in a few tens of milliseconds. SIGNIFICANCE STATEMENT:
      Understanding how sensory information is processed requires different approaches
      that span multiple levels of investigation from genes to neurons to behavior.
      Limits on behavioral performance constrain the possible neural mechanisms
      responsible for specific computations. Using a novel behavioral paradigm, we
      established that mice can make decisions about odor intensity surprisingly fast.
      After accounting for sensory and motor delays, the limit on some olfactory neural
      computations can be as low as a few tens of milliseconds, which suggests that
      only the first action potentials across a population of neurons contribute to
      these computations.

PMID- 26290244
TI  - "Visual" Cortex Responds to Spoken Language in Blind Children.
AB  - Plasticity in the visual cortex of blind individuals provides a rare window into
      the mechanisms of cortical specialization. In the absence of visual input,
      occipital ("visual") brain regions respond to sound and spoken language. Here, we
      examined the time course and developmental mechanism of this plasticity in blind
      children. Nineteen blind and 40 sighted children and adolescents (4-17 years old)
      listened to stories and two auditory control conditions (unfamiliar foreign
      speech, and music). We find that "visual" cortices of young blind (but not
      sighted) children respond to sound. Responses to nonlanguage sounds increased
      between the ages of 4 and 17. By contrast, occipital responses to spoken language
      were maximal by age 4 and were not related to Braille learning. These findings
      suggest that occipital plasticity for spoken language is independent of
      plasticity for Braille and for sound. We conclude that in the absence of visual
      input, spoken language colonizes the visual system during brain development. Our
      findings suggest that early in life, human cortex has a remarkably broad
      computational capacity. The same cortical tissue can take on visual perception
      and language functions. SIGNIFICANCE STATEMENT: Studies of plasticity provide key
      insights into how experience shapes the human brain. The "visual" cortex of
      adults who are blind from birth responds to touch, sound, and spoken language. To
      date, all existing studies have been conducted with adults, so little is known
      about the developmental trajectory of plasticity. We used fMRI to study the
      emergence of "visual" cortex responses to sound and spoken language in blind
      children and adolescents. We find that "visual" cortex responses to sound
      increase between 4 and 17 years of age. By contrast, responses to spoken language
      are present by 4 years of age and are not related to Braille-learning. These
      findings suggest that, early in development, human cortex can take on a
      strikingly wide range of functions.

PMID- 26290242
TI  - Experience-Dependent Regulation of Dentate Gyrus Excitability by Adult-Born
      Granule Cells.
AB  - Behavioral studies have established a role for adult-born dentate granule cells
      in discriminating between similar memories. However, it is unclear how these
      cells mediate memory discrimination. Excitability is enhanced in maturing adult
      born neurons, spurring the hypothesis that the activity of these cells "directly"
      encodes and stores memories. An alternative hypothesis posits that maturing
      neurons "indirectly" contribute to memory encoding by regulating excitation
      inhibition balance. We evaluated these alternatives by using dentate-sensitive
      active place avoidance tasks to assess experience-dependent changes in dentate
      field potentials in the presence and absence of neurogenesis. Before training, X
      ray ablation of adult neurogenesis-reduced dentate responses to perforant-path
      stimulation and shifted EPSP-spike coupling leftward. These differences were
      unchanged after place avoidance training with the shock zone in the initial
      location, which both groups learned to avoid equally well. In contrast, sham
      treated mice decreased dentate responses and shifted EPSP-spike coupling leftward
      after the shock zone was relocated, whereas X-irradiated mice failed to show
      these changes in dentate function and were impaired on this test of memory
      discrimination. During place avoidance, excitation-inhibition coupled neural
      synchrony in dentate local field potentials was reduced in X-irradiated mice,
      especially in the theta band. The difference was most prominent during conflict
      learning, which is impaired in the X-irradiated mice. These findings indicate
      that maturing adult-born neurons regulate both functional network plasticity in
      response to memory discrimination and dentate excitation-inhibition coordination.
      The most parsimonious interpretation of these results is that adult neurogenesis
      indirectly regulates hippocampal information processing. SIGNIFICANCE STATEMENT:
      Adult-born neurons in the hippocampal dentate gyrus are important for flexibly
      using memories, but the mechanism is controversial. Using tests of hippocampus
      dependent place avoidance learning and dentate electrophysiology in mice with
      normal or ablated neurogenesis, we find that maturing adult-born neurons are
      crucial only when memory must be used flexibly, and that these neurons regulate
      dentate gyrus synaptic and spiking responses to neocortical input rather than
      directly storing information, as has been proposed. A day after learning to avoid
      the initial or changed locations of shock, the dentate synaptic responses are
      enhanced or suppressed, respectively, unlike mice lacking adult neurogenesis,
      which did not change. The contribution of adult neurogenesis to memory is
      indirect, by regulating dentate excitation-inhibition coupling.

PMID- 26290245
TI  - Knock-In Mice with NOP-eGFP Receptors Identify Receptor Cellular and Regional
      Localization.
AB  - The nociceptin/orphanin FQ (NOP) receptor, the fourth member of the opioid
      receptor family, is involved in many processes common to the opioid receptors
      including pain and drug abuse. To better characterize receptor location and
      trafficking, knock-in mice were created by inserting the gene encoding enhanced
      green fluorescent protein (eGFP) into the NOP receptor gene (Oprl1) and producing
      mice expressing a functional NOP-eGFP C-terminal fusion in place of the native
      NOP receptor. The NOP-eGFP receptor was present in brain of homozygous knock-in
      animals in concentrations somewhat higher than in wild-type mice and was
      functional when tested for stimulation of [(35)S]GTPgammaS binding in vitro and
      in patch-clamp electrophysiology in dorsal root ganglia (DRG) neurons and
      hippocampal slices. Inhibition of morphine analgesia was equivalent when tested
      in knock-in and wild-type mice. Imaging revealed detailed neuroanatomy in brain,
      spinal cord, and DRG and was generally consistent with in vitro autoradiographic
      imaging of receptor location. Multicolor immunohistochemistry identified cells
      coexpressing various spinal cord and DRG cellular markers, as well as
      coexpression with MU-opioid receptors in DRG and brain regions. Both in tissue
      slices and primary cultures, the NOP-eGFP receptors appear throughout the cell
      body and in processes. These knock-in mice have NOP receptors that function both
      in vitro and in vivo and appear to be an exceptional tool to study receptor
      neuroanatomy and correlate with NOP receptor function. SIGNIFICANCE STATEMENT:
      The NOP receptor, the fourth member of the opioid receptor family, is involved in
      pain, drug abuse, and a number of other CNS processes. The regional and cellular
      distribution has been difficult to determine due to lack of validated antibodies
      for immunohistochemical analysis. To provide a new tool for the investigation of
      receptor localization, we have produced knock-in mice with a fluorescent-tagged
      NOP receptor in place of the native NOP receptor. These knock-in mice have NOP
      receptors that function both in vitro and in vivo and have provided a detailed
      characterization of NOP receptors in brain, spinal cord, and DRG neurons. They
      appear to be an exceptional tool to study receptor neuroanatomy and correlate
      with NOP receptor function.

PMID- 26290246
TI  - Evidence that Subanesthetic Doses of Ketamine Cause Sustained Disruptions of NMDA
      and AMPA-Mediated Frontoparietal Connectivity in Humans.
AB  - Following the discovery of the antidepressant properties of ketamine, there has
      been a recent resurgence in the interest in this NMDA receptor antagonist.
      Although detailed animal models of the molecular mechanisms underlying ketamine's
      effects have emerged, there are few MEG/EEG studies examining the acute
      subanesthetic effects of ketamine infusion in man. We recorded 275 channel MEG in
      two experiments (n = 25 human males) examining the effects of subanesthetic
      ketamine infusion. MEG power spectra revealed a rich set of significant
      oscillatory changes compared with placebo sessions, including decreases in
      occipital, parietal, and anterior cingulate alpha power, increases in medial
      frontal theta power, and increases in parietal and cingulate cortex high gamma
      power. Each of these spectral effects demonstrated their own set of temporal
      dynamics. Dynamic causal modeling of frontoparietal connectivity changes with
      ketamine indicated a decrease in NMDA and AMPA-mediated frontal-to-parietal
      connectivity. AMPA-mediated connectivity changes were sustained for up to 50 min
      after ketamine infusion had ceased, by which time perceptual distortions were
      absent. The results also indicated a decrease in gain of parietal pyramidal
      cells, which was correlated with participants' self-reports of blissful state.
      Based on these results, we suggest that the antidepressant effects of ketamine
      may depend on its ability to change the balance of frontoparietal connectivity
      patterns. SIGNIFICANCE STATEMENT: In this paper, we found that subanesthetic
      doses of ketamine, similar to those used in antidepressant studies, increase
      anterior theta and gamma power but decrease posterior theta, delta, and alpha
      power, as revealed by magnetoencephalographic recordings. Dynamic causal modeling
      of frontoparietal connectivity changes with ketamine indicated a decrease in NMDA
      and AMPA-mediated frontal-to-parietal connectivity. AMPA-mediated connectivity
      changes were sustained for up to 50 min after ketamine infusion had ceased, by
      which time perceptual distortions were absent. The results also indicated a
      decrease in gain of parietal pyramidal cells, which was correlated with
      participants' self-reports of blissful state. The alterations in frontoparietal
      connectivity patterns we observe here may be important in generating the
      antidepressant response to ketamine.

PMID- 26290247
TI  - Netrin1-DCC-Mediated Attraction Guides Post-Crossing Commissural Axons in the
      Hindbrain.
AB  - Commissural axons grow along precise trajectories that are guided by several cues
      secreted from the ventral midline. After initial attraction to the floor plate
      using Netrin1 activation of its main attractive receptor, DCC (deleted in
      colorectal cancer), axons cross the ventral midline, and many turn to grow
      longitudinally on the contralateral side. After crossing the midline, axons are
      thought to lose their responsiveness to Netrin1 and become sensitive to midline
      Slit-Robo repulsion. We aimed to address the in vivo significance of Netrin1 in
      guiding post-crossing axon trajectories in mouse embryos. Surprisingly, in
      contrast to the spinal cord, Netrin1 and DCC mutants had abundant commissural
      axons crossing in the hindbrain. In Netrin1 and DCC mutants, many post-crossing
      axons made normal turns to grow longitudinally, but projected abnormally at
      angles away from the midline. In addition, exposure of cultured hindbrain
      explants to ectopic Netrin1 caused attractive deflection of post-crossing axons.
      Thus, Netrin1-DCC signaling is not required to attract pre-crossing axons toward
      the hindbrain floor plate, but is active in post-crossing guidance. Also in
      contrast with spinal cord, analysis of hindbrain post-crossing axons in Robo1/2
      mutant embryos showed that Slit-Robo repulsive signaling was not required for
      post-crossing trajectories. Our findings show that Netrin1-DCC attractive
      signaling, but not Slit-Robo repulsive signaling, remains active in hindbrain
      post-crossing commissural axons to guide longitudinal trajectories, suggesting
      surprising regional diversity in commissural axon guidance mechanisms.
      SIGNIFICANCE STATEMENT: The left and right sides of the brainstem and spinal cord
      are connected primarily by axon fibers that grow across the ventral midline, and
      then away on the other side to their targets. Based on spinal cord, axons are
      initially attracted by diffusible attractive protein signals to approach and
      cross the midline, and then are thought to switch to repulsive cues to grow away
      on the opposite side. Our results in the hindbrain show that the major midline
      attractant, Netrin1, is not required for midline crossing. However, the post
      crossing axons depend on Netrin1 attraction to set their proper trajectories on
      the other side. Overall, these findings suggest that commissural axons use
      distinct mechanisms to navigate in different CNS regions.

PMID- 26290248
TI  - Inactivation of Parietal Reach Region Affects Reaching But Not Saccade Choices in
      Internally Guided Decisions.
AB  - The posterior parietal cortex (PPC) has traditionally been considered important
      for awareness, spatial perception, and attention. However, recent findings
      provide evidence that the PPC also encodes information important for making
      decisions. These findings have initiated a running argument of whether the PPC is
      critically involved in decision making. To examine this issue, we reversibly
      inactivated the parietal reach region (PRR), the area of the PPC that is
      specialized for reaching movements, while two monkeys performed a memory-guided
      reaching or saccade task. The task included choices between two equally rewarded
      targets presented simultaneously in opposite visual fields. Free-choice trials
      were interleaved with instructed trials, in which a single cue presented in the
      peripheral visual field defined the reach and saccade target unequivocally. We
      found that PRR inactivation led to a strong reduction of contralesional choices,
      but only for reaches. On the other hand, saccade choices were not affected by PRR
      inactivation. Importantly, reaching and saccade movements to single instructed
      targets remained largely intact. These results cannot be explained as an effector
      nonspecific deficit in spatial attention or awareness, since the temporary
      "lesion" had an impact only on reach choices. Hence, the PPR is a part of a
      network for reach decisions and not just reach planning. SIGNIFICANCE STATEMENT:
      There has been an ongoing debate on whether the posterior parietal cortex (PPC)
      represents only spatial awareness, perception, and attention or whether it is
      also involved in decision making for actions. In this study we explore whether
      the parietal reach region (PRR), the region of the PPC that is specialized for
      reaches, is involved in the decision process. We inactivated the PRR while two
      monkeys performed reach and saccade choices between two targets presented
      simultaneously in both hemifields. We found that inactivation affected only the
      reach choices, while leaving saccade choices intact. These results cannot be
      explained as a deficit in attention, since the temporary lesion affected only the
      reach choices. Thus, PRR is a part of a network for making reach decisions.

PMID- 26290249
TI  - Experience Modulates the Effects of Histone Deacetylase Inhibitors on Gene and
      Protein Expression in the Hippocampus: Impaired Plasticity in Aging.
AB  - The therapeutic potential of histone deacetylase inhibitor (HDACi) treatment has
      attracted considerable attention in the emerging area of cognitive
      neuroepigenetics. The possibility that ongoing cognitive experience importantly
      regulates the cell biological effects of HDACi administration, however, has not
      been systematically examined. In an initial experiment addressing this issue, we
      tested whether water maze training influences the gene expression response to
      acute systemic HDACi administration in the young adult rat hippocampus. Training
      powerfully modulated the response to HDACi treatment, increasing the total number
      of genes regulated to nearly 3000, including many not typically linked to neural
      plasticity, compared with <300 following HDACi administration alone. Although
      water maze training itself also regulated nearly 1800 genes, the specific mRNAs,
      gene networks, and biological pathways involved were largely distinct when the
      same experience was provided together with HDACi administration. Next, we tested
      whether the synaptic protein response to HDACi treatment is similarly dependent
      on recent cognitive experience, and whether this plasticity is altered in aged
      rats with memory impairment. Whereas synaptic protein labeling in the young
      hippocampus was selectively increased when HDACi administration was provided in
      conjunction with water maze training, combined treatment had no effect on
      synaptic proteins in the aged hippocampus. Our findings indicate that ongoing
      experience potently regulates the molecular consequences of HDACi treatment and
      that the interaction of recent cognitive experience with histone acetylation
      dynamics is disrupted in the aged hippocampus. SIGNIFICANCE STATEMENT: The
      possibility that interventions targeting epigenetic regulation could be effective
      in treating a range of neurodegenerative disorders has attracted considerable
      interest. Here we demonstrate in the rat hippocampus that ongoing experience
      powerfully modifies the molecular response to one such intervention, histone
      deacetylase inhibitor (HDACi) administration. A single learning episode
      dramatically shifts the gene expression profile induced by acute HDACi treatment,
      yielding a qualitatively distinct hippocampal transcriptome compared with the
      influence of behavioral training alone. The downstream synaptic protein response
      to HDACi administration is similarly experience-dependent, and we report that
      this plasticity is disrupted in the aged hippocampus. The findings highlight that
      accommodating the modulatory influence of ongoing experience represents a
      challenge for therapeutic development in the area of cognitive neuroepigenetics.

PMID- 26290250
TI  - Brain Structural Integrity and Intrinsic Functional Connectivity Forecast 6 Year
      Longitudinal Growth in Children's Numerical Abilities.
AB  - Early numerical proficiency lays the foundation for acquiring quantitative skills
      essential in today's technological society. Identification of cognitive and brain
      markers associated with long-term growth of children's basic numerical
      computation abilities is therefore of utmost importance. Previous attempts to
      relate brain structure and function to numerical competency have focused on
      behavioral measures from a single time point. Thus, little is known about the
      brain predictors of individual differences in growth trajectories of numerical
      abilities. Using a longitudinal design, with multimodal imaging and machine
      learning algorithms, we investigated whether brain structure and intrinsic
      connectivity in early childhood are predictive of 6 year outcomes in numerical
      abilities spanning childhood and adolescence. Gray matter volume at age 8 in
      distributed brain regions, including the ventrotemporal occipital cortex (VTOC),
      the posterior parietal cortex, and the prefrontal cortex, predicted longitudinal
      gains in numerical, but not reading, abilities. Remarkably, intrinsic
      connectivity analysis revealed that the strength of functional coupling among
      these regions also predicted gains in numerical abilities, providing novel
      evidence for a network of brain regions that works in concert to promote
      numerical skill acquisition. VTOC connectivity with posterior parietal, anterior
      temporal, and dorsolateral prefrontal cortices emerged as the most extensive
      network predicting individual gains in numerical abilities. Crucially, behavioral
      measures of mathematics, IQ, working memory, and reading did not predict
      children's gains in numerical abilities. Our study identifies, for the first
      time, functional circuits in the human brain that scaffold the development of
      numerical skills, and highlights potential biomarkers for identifying children at
      risk for learning difficulties. SIGNIFICANCE STATEMENT: Children show substantial
      individual differences in math abilities and ease of math learning. Early
      numerical abilities provide the foundation for future academic and professional
      success in an increasingly technological society. Understanding the early
      identification of poor math skills has therefore taken on great significance.
      This work provides important new insights into brain structure and connectivity
      measures that can predict longitudinal growth of children's math skills over a 6
      year period, and may eventually aid in the early identification of children who
      might benefit from targeted interventions.

PMID- 26290253
TI  - Overstimulation Fatal for Cancer Cells.

PMID- 26290251
TI  - The Role of Frontal Cortical and Medial-Temporal Lobe Brain Areas in Learning a
      Bayesian Prior Belief on Reversals.
AB  - Reversal learning has been extensively studied across species as a task that
      indexes the ability to flexibly make and reverse deterministic stimulus-reward
      associations. Although various brain lesions have been found to affect
      performance on this task, the behavioral processes affected by these lesions have
      not yet been determined. This task includes at least two kinds of learning.
      First, subjects have to learn and reverse stimulus-reward associations in each
      block of trials. Second, subjects become more proficient at reversing choice
      preferences as they experience more reversals. We have developed a Bayesian
      approach to separately characterize these two learning processes. Reversal of
      choice behavior within each block is driven by a combination of evidence that a
      reversal has occurred, and a prior belief in reversals that evolves with
      experience across blocks. We applied the approach to behavior obtained from 89
      macaques, comprising 12 lesion groups and a control group. We found that animals
      from all of the groups reversed more quickly as they experienced more reversals,
      and correspondingly they updated their prior beliefs about reversals at the same
      rate. However, the initial values of the priors that the various groups of
      animals brought to the task differed significantly, and it was these initial
      priors that led to the differences in behavior. Thus, by taking a Bayesian
      approach we find that variability in reversal-learning performance attributable
      to different neural systems is primarily driven by different prior beliefs about
      reversals that each group brings to the task. SIGNIFICANCE STATEMENT: The ability
      to use prior knowledge to adapt choice behavior is critical for flexible decision
      making. Reversal learning is often studied as a form of flexible decision making.
      However, prior studies have not identified which brain regions are important for
      the formation and use of prior beliefs to guide choice behavior. Here we develop
      a Bayesian approach that formally characterizes learning set as a concept, and we
      show that, in macaque monkeys, the amygdala and medial prefrontal cortex have a
      role in establishing an initial belief about the stability of the reward
      environment.

PMID- 26290254
TI  - Further analyses support the association between light eye color and alcohol
      dependence.

PMID- 26290255
TI  - Factors predicting parents' adaptation when supporting their young adult during a
      first-episode psychosis.
AB  - AIM: The objective is to identify the factors that predict how well parents will
      adapt when supporting their adult child experiencing a FEP. METHODS: The study
      was conducted in Quebec city with 58 parents and stepparents who received
      services from a specialized clinic for treating psychotic illnesses in the early
      stages. Participants filled in four measuring instruments during a standardized
      telephone interview. Based on the model being proposed, bivariate analyses and
      linear regression models were carried out to identify factors that predict how
      parents will adapt. RESULTS: The analyses allowed us to determine that the
      factors revealing the severity of the illness and the vulnerability of the young
      person predict the negative aspects of the parents' experience (R2  = 0.39, P <=
      0.000), whereas the personal factors related to the parents themselves
      essentially predict the positive aspects (R2  = 0.51, P <= 0.001). The
      empowerment can be predicted by the combined effect of the positive aspects of
      the parents' experience and their coping strategies, more specifically those
      related to family intervention (R2  = 0.60, P <= 0.001), whereas the parents'
      social functioning is linked to their active participation in a family
      association (R2 = 0.14, P <= 0.006). CONCLUSION: This study contributes to how we
      think of parents' adaptation as it suggests a model that takes the positive
      aspects into account, associated with the role of support, along with family
      intervention strategies offered by social workers. Adaptation that is
      conceptualized using two dependent variables, empowerment and social functioning,
      allows to identify intervention targets that will be beacons of hope for both the
      parents and the young people with psychosis, while encouraging early intervention
      and partnership practices between services and family members.

PMID- 26290256
TI  - Increased habituation to painful stimuli: a self-protective mechanism during
      prolonged wakefulness?

PMID- 26290257
TI  - Compression at myofascial trigger points for the management of acute low back
      pain.

PMID- 26290258
TI  - Tales from the war on error: the art and science of curating QSAR data.
AB  - Curating the data underlying quantitative structure-activity relationship models
      is a never-ending struggle. Some curation can now be automated but much cannot,
      especially where data as complex as those pertaining to molecular absorption,
      distribution, metabolism, excretion, and toxicity are concerned (vide infra). The
      authors discuss some particularly challenging problem areas in terms of specific
      examples involving experimental context, incompleteness of data, confusion of
      units, problematic nomenclature, tautomerism, and misapplication of automated
      structure recognition tools. 

PMID- 26290259
TI  - Association of hepatic oxidative stress and iron dysregulation with HCC
      development after interferon therapy in chronic hepatitis C.
AB  - BACKGROUND: Oxidative stress may play pathogenic roles in the mechanisms
      underlying chronic hepatitis C (CHC). The impact of excessive oxidative stress
      and iron dysregulation on the development of hepatocellular carcinoma (HCC) after
      interferon therapy has not been established. METHODS: We investigated the impact
      of oxidative stress and iron deposition on HCC development after therapy with
      pegylated interferon (PegIFN)+ribavirin in CHC patients. Systemic and
      intracellular iron homeostasis was evaluated in liver tissues, peripheral blood
      mononuclear cells and sera. RESULTS: Of 203 patients enrolled, 13 developed HCC
      during the 5.6-year follow-up. High hepatic 8-hydroxy-2-deoxyguanosine (8-OHdG)
      levels were significantly associated with HCC development in multivariate
      analysis (p=0.0012) which was also significantly correlated with severity of
      hepatic iron deposition before therapy (p<0.0001). Systemic and intracellular
      iron regulators of hepcidin and F-box and leucine-rich repeat protein 5 (FBXL5)
      expression levels were significantly suppressed in CHC patients (p=0.0032 and
      p=0.016, respectively) despite their significantly higher levels of serum iron
      and ferritin compared with controls. However, intracellular iron regulators of
      FBXL5 and iron regulatory proteins were regulated in balance with hepatic iron
      deposition. Significant correlations were observed among IL-6, bone morphogenetic
      protein 6, hepcidin and ferroportin, as regards systemic iron regulation.
      CONCLUSIONS: Measurement of hepatic oxidative stress before antiviral therapy is
      useful for the prediction of HCC development after interferon therapy. Low
      baseline levels of the intracellular iron regulators of FBXL5 in addition to a
      suppressed hepcidin level might be associated with severe hepatic iron deposition
      in CHC patients. TRIAL REGISTRATION NUMBER: UMIN 000001031.

PMID- 26290260
TI  - Expression and prognostic value of putative cancer stem cell markers CD117 and
      CD15 in choroidal and ciliary body melanoma.
AB  - AIMS: The aim of the present study was to immunohistochemically investigate the
      expression and prognostic significance of putative cancer stem cell markers CD117
      (c-kit), CD34, CD20 and CD15 in a cohort of patients with primary choroidal and
      ciliary body melanoma. METHODS: The immunohistochemical expression of these
      markers was evaluated using 3,3'-diaminobenzidine tetrahydrochloride (DAB) and 3
      amino-9-ethylcarbazole (AEC) chromogens on paraffin-embedded tissue samples from
      40 patients who underwent enucleation in the period from 1985 through 2000.
      Thirty-one patients had adequate tissue specimens for the analysis. RESULTS:
      CD117 overexpression was observed in 12 of the 31 samples (39%) when AEC
      chromogen was used and in 14 of 26 (54%) samples when DAB was used. CD15
      positivity was seen in three out of 30 (10%) samples with AEC and in six out of
      26 (23%) samples with DAB. CD20 and CD34 exhibited no positivity in the tested
      samples. During the average follow-up time of 8.7 years (range 0.5-22 years), 17
      patients (55%) died due to metastatic disease. The Kaplan-Meier plots showed a
      significantly shorter overall and disease-free survival in CD117-positive
      patients when the AEC chromogen was used. CD15 expression was not associated with
      patients' survival. In multivariate analysis, patients expressing the CD117 AEC
      had 4.13 times higher risk of lethal outcome in comparison with CD117 AEC
      negative patients. CONCLUSIONS: Our retrospective cohort study has for the first
      time demonstrated a small proportion of CD15-positive uveal melanomas. CD117 AEC
      overexpression was associated with a worse outcome in patients with choroidal and
      ciliary body melanoma. Further studies should confirm the validity of these
      observations and their potential for targeted treatment modalities.

PMID- 26290261
TI  - Megakaryocytic hyperplasia in myeloproliferative neoplasms is driven by
      disordered proliferative, apoptotic and epigenetic mechanisms.
AB  - AIMS: Myeloproliferative neoplasms (MPN) are a heterogeneous group of clonal
      proliferative bone marrow diseases characterised by extensive megakaryocytic
      hyperplasia and morphological atypia. Despite knowledge of genomic defects, the
      pathobiological processes driving these megakaryocytic abnormalities in MPN
      remain poorly explained. We have explored the proliferative, apoptotic and
      epigenetic profiles of megakaryocytes in human MPN. METHODS: Immunohistochemical
      staining was performed on bone marrow trephine biopsies of 81 MPN (with and
      without JAK2(V617F) and CALR mutations) and 15 normal controls to assess the
      megakaryocytic expression of biomarkers associated with proliferation (Ki67),
      apoptosis (Bcl-XL, BNIP-3) and epigenetic regulation (EZH2, SUZ12). RESULTS:
      Myeloproliferative megakaryocytes showed significantly greater expression of
      proliferative Ki67 and anti-apoptotic Bcl-XL, reduced pro-apoptotic BNIP-3 and
      increased SUZ12 compared with controls. In essential thrombocythaemia, large
      giant megakaryocytes with hyperlobated nuclei showed a trend towards a
      proliferative signature. In contrast, myelofibrotic megakaryocytes with condensed
      nuclear chromatin, and cases with CALR mutations, had significant reductions in
      pro-apoptotic BNIP-3. CONCLUSIONS: Uncontrolled megakaryocytic expansion in MPN
      results from a combination of increased proliferation, attenuated apoptosis and
      defective epigenetic regulation with CALR mutations favouring apoptotic failure.
      The higher platelet counts reported to be seen in MPN with CALR mutations may be
      due to greater dysregulation of megakaryocyte apoptosis.

PMID- 26290264
TI  - The prevalence, measurement, and treatment of the cognitive dimension/domain in
      major depressive disorder.
AB  - Insufficient outcomes amongst adults with major depressive disorder (MDD) provide
      the impetus to identify and refine therapeutic targets that are most critical to
      outcome from patient, provider, and societal perspectives. Towards this aim, a
      pivotal shift towards the transnosological domain, cognition, is occurring in the
      study of MDD and other brain disorders. This paper aims to provide a framework
      for conceptualizing and prioritizing cognitive function amongst adults with MDD
      with a particular view to provide a conceptual framework for research and
      clinical priorities. We also summarize extant data pertaining to psychotropic
      effects, notably antidepressants, on the cognitive dimension/domain. This
      narrative review was based on articles identified through a PubMed/MEDLINE search
      of all English-language articles published between January 1966 and October 2014.
      The search words were major depressive disorder, depression, unipolar depression,
      cognition, cognitive dysfunction, cognitive deficit, and cognitive function. The
      search was supplemented with a manual review of relevant references. The
      selection of articles for inclusion in this review was based on overall
      methodological quality as well as on their pertinence to informing the framework
      described herein. Cognitive dysfunction in MDD is a discrete domain subserved by
      discrete yet overlapping substrates. There is a need to provide a glossary of
      terms commonly employed in the cognition literature for consensus as to the
      appropriate screening, measurement, and monitoring tools. The guiding principle
      of measurement-based care should include systematic assessment and measurement of
      cognition in subpopulations with MDD, as a tactic to improve outcome. Relatively
      few treatment strategies have demonstrated efficacy specifically for the
      cognitive domain in MDD. The antidepressant vortioxetine has replicated evidence
      of specific pro-cognitive effects in adults with MDD across multiple subdomains
      of cognitive function. Vortioxetine is a novel antidepressant that is
      hypothesized to act through a combination of direct effects on receptor activity
      and serotonin receptor inhibition, as well as other systems. Pro-cognitive
      effects for other US FDA-approved agents are suggested, but pseudospecificity has
      not been excluded as a possible explanation of their beneficial effects on
      cognitive function. A disparate assortment of other agents are currently under
      investigation for possible benefit in mitigating cognitive deficits and improving
      cognitive performance (e.g., intranasal insulin, erythropoietin, anti
      inflammatory agents). Non-pharmacological approaches including, but not limited
      to, cognitive remediation (CR), aerobic exercise, and neuromodulation are
      promising. 

PMID- 26290266
TI  - Venous retinal oxygen saturation is independent from nerve fibre layer thickness
      in glaucoma patients.

PMID- 26290265
TI  - Ubiquitin-specific protease 24 negatively regulates abscisic acid signalling in
      Arabidopsis thaliana.
AB  - Abscisic acid (ABA) is an important plant hormone integrating environmental
      stress and plant growth. Protein ubiquitination and deubiquitination are
      reversible processes catalysed by E3 ubiquitin ligase and deubiquitinating
      enzyme, respectively. Lots of E3 ubiquitin ligase and transcriptional factors
      modified by ubiquitination were reported to modulate ABA signalling. However, no
      deubiquitinating enzyme has been identified that functions in ABA signalling
      until now. Here, we isolated an ABA overly sensitive mutant, ubp24, in which the
      gene encoding ubiquitin-specific protease 24 (UBP24, At4g30890) was disrupted by
      a T-DNA insertion. The ubp24 mutant was hypersensitive to ABA and salt stress in
      both post-germinative growth and seedling growth. However, stomata closure in the
      ubp24 mutant was less sensitive to ABA, and the ubp24 mutant showed drought
      sensitivity. UBP24 possessed deubiquitinating enzyme activity, and the activity
      was essential for UBP24 function. Additionally, UBP24 formed homodimer in vivo.
      UBP24 was genetically upstream of ABI2, and the phosphatase activity of protein
      phosphatase 2C was decreased in the ubp24 mutant compared with the wild type in
      the presence of ABA. These results uncover an important regulatory role for the
      ubiquitin-specific protease in response to ABA and salt stress in plant. 

PMID- 26290267
TI  - Neuroprotection of Ischemic Preconditioning is Mediated by Anti-inflammatory, Not
      Pro-inflammatory, Cytokines in the Gerbil Hippocampus Induced by a Subsequent
      Lethal Transient Cerebral Ischemia.
AB  - Ischemic preconditioning (IPC) induced by sublethal transient cerebral ischemia
      could reduce neuronal damage/death following a subsequent lethal transient
      cerebral ischemia. We, in this study, compared expressions of interleukin (IL)-2
      and tumor necrosis factor (TNF)-alpha as pro-inflammatory cytokines, and IL-4 and
      IL-13 as anti-inflammatory cytokines in the gerbil hippocampal CA1 region between
      animals with lethal ischemia and ones with IPC followed by lethal ischemia. In
      the animals with lethal ischemia, pyramidal neurons in the stratum pyramidale
      (SP) of the hippocampal CA1 region were dead at 5 days post-ischemia; however,
      IPC protected the CA1 pyramidal neurons from lethal ischemic injury. Expressions
      of all cytokines were significantly decreased in the SP after lethal ischemia and
      hardly detected in the SP at 5 days post-ischemia because the CA1 pyramidal
      neurons were dead. IPC increased expressions of anti-inflammatory cytokines (IL-4
      and IL-13) in the stratum pyramidale of the CA1 region following no lethal
      ischemia (sham-operation), and the increased expressions of IL-4 and IL-13 by IPC
      were continuously maintained is the SP of the CA1 region after lethal ischemia.
      However, pro-inflammatory cytokines (IL-2 and TNF-alpha) in the SP of the CA1
      region were similar those in the sham-operated animals with IPC, and the IL-4 and
      IL-13 expressions in the SP were maintained after lethal ischemia. In conclusion,
      this study shows that anti-inflammatory cytokines significantly increased and
      longer maintained by IPC and this might be closely associated with
      neuroprotection after lethal transient cerebral ischemia. 

PMID- 26290263
TI  - Propofol: a review of its role in pediatric anesthesia and sedation.
AB  - Propofol is an intravenous agent used commonly for the induction and maintenance
      of anesthesia, procedural, and critical care sedation in children. The mechanisms
      of action on the central nervous system involve interactions at various
      neurotransmitter receptors, especially the gamma-aminobutyric acid A receptor.
      Approved for use in the USA by the Food and Drug Administration in 1989, its use
      for induction of anesthesia in children less than 3 years of age still remains
      off-label. Despite its wide use in pediatric anesthesia, there is conflicting
      literature about its safety and serious adverse effects in particular subsets of
      children. Particularly as children are not "little adults", in this review, we
      emphasize the maturational aspects of propofol pharmacokinetics. Despite the
      myriad of propofol pharmacokinetic-pharmacodynamic studies and the ability to use
      allometrical scaling to smooth out differences due to size and age, there is no
      optimal model that can be used in target controlled infusion pumps for providing
      closed loop total intravenous anesthesia in children. As the commercial
      formulation of propofol is a nutrient-rich emulsion, the risk for bacterial
      contamination exists despite the Food and Drug Administration mandating addition
      of antimicrobial preservative, calling for manufacturers' directions to discard
      open vials after 6 h. While propofol has advantages over inhalation anesthesia
      such as less postoperative nausea and emergence delirium in children, pain on
      injection remains a problem even with newer formulations. Propofol is known to
      depress mitochondrial function by its action as an uncoupling agent in oxidative
      phosphorylation. This has implications for children with mitochondrial diseases
      and the occurrence of propofol-related infusion syndrome, a rare but seriously
      life-threatening complication of propofol. At the time of this review, there is
      no direct evidence in humans for propofol-induced neurotoxicity to the infant
      brain; however, current concerns of neuroapoptosis in developing brains induced
      by propofol persist and continue to be a focus of research. 

PMID- 26290268
TI  - Molecular Changes in Sub-lesional Muscle Following Acute Phase of Spinal Cord
      Injury.
AB  - To clarify the molecular changes of sublesional muscle in the acute phase of
      spinal cord injury (SCI), a moderately severe injury (40 g cm) was induced in the
      spinal cord (T10 vertebral level) of adult male Sprague-Dawley rats (injury) and
      compared with sham (laminectomy only). Rats were sacrificed at 48 h (acute) post
      injury, and gastrocnemius muscles were excised. Morphological examination
      revealed no significant changes in the muscle fiber diameter between the sham and
      injury rats. Western blot analyses performed on the visibly red, central portion
      of the gastrocnemius muscle showed significantly higher expression of muscle
      specific E3 ubiquitin ligases (muscle ring finger-1 and muscle atrophy f-box) and
      significantly lower expression of phosphorylated Akt-1/2/3 in the injury group
      compared to the sham group. Cyclooxygenase 2, tumor necrosis factor alpha (TNF
      alpha), and caspase-1, also had a significantly higher expression in the injury
      group; although, the mRNA levels of TNF-alpha and IL-6 did not show any
      significant difference between the sham and injury groups. These results suggest
      activation of protein degradation, deactivation of protein synthesis, and
      development of inflammatory reaction occurring in the sublesional muscles in the
      acute phase of SCI before overt muscle atrophy is seen.

PMID- 26290269
TI  - A computer simulation method for low-dose CT images by use of real high-dose
      images: a phantom study.
AB  - Practical simulations of low-dose CT images have a possibility of being helpful
      means for optimization of the CT exposure dose. Because current methods reported
      by several researchers are limited to specific vendor platforms and generally
      rely on raw sinogram data that are difficult to access, we have developed a new
      computerized scheme for producing simulated low-dose CT images from real high
      dose images without use of raw sinogram data or of a particular phantom. Our
      computerized scheme for low-dose CT simulation was based on the addition of a
      simulated noise image to a real high-dose CT image reconstructed by the filtered
      back-projection algorithm. First, a sinogram was generated from the forward
      projection of a high-dose CT image. Then, an additional noise sinogram resulting
      from use of a reduced exposure dose was estimated from a predetermined noise
      model. Finally, a noise CT image was reconstructed with a predetermined filter
      and was added to the real high-dose CT image to create a simulated low-dose CT
      image. The noise power spectrum and modulation transfer function of the simulated
      low-dose images were very close to those of the real low-dose images. In order to
      confirm the feasibility of our method, we applied this method to clinical cases
      which were examined with the high dose initially and then followed with a low
      dose CT. In conclusion, our proposed method could simulate the low-dose CT images
      from their real high-dose images with sufficient accuracy and could be used for
      determining the optimal dose setting for various clinical CT examinations. 

PMID- 26290270
TI  - Bayesian Analysis for Genetic Architectures of Body Weights and Morphological
      Traits Using Distorted Markers in Japanese Flounder Paralichthys olivaceus.
AB  - A doubled haploids (DH) population of 160 individuals is constructed by using
      mitotic gynogenetics for the study of genetic architectures of the body weight
      and morphological traits in Japanese flounder. Each DH individual is genotyped
      for 458 SSR markers, 222 of which segregate distortionally. By modifying
      conditional probabilities of quantitative trait locus (QTL) genotypes on the
      distorted flanking markers, Bayesian model selection is used to dissect genetic
      architectures for the traits. As a result, we identify 42 main-effect QTLs on
      chromosomes 5, 6, 7, 8, 9, 10, 15, 20, 21, 22, and 59 pairs of interacting QTLs.
      Among these detected QTLs, the largest interacting QTL is between chromosome 6
      and chromosome 9 and accounts for 25.196 % of phenotypic variance for body
      weights and in a similar trend. Also, many QTLs show pleiotropic effects. The QTL
      on chromosome 9 simultaneously governs seven traits, BL, BH, FL, HL, PFL, HW, and
      CW. As compared to method using the uncorrected conditional probabilities of QTL
      genotypes, our method using corrected conditional probabilities can detect more
      interacting QTLs for the traits.

PMID- 26290271
TI  - Assessment of the Efficiency of Tobacco Cessation Counseling in Primary Care.
AB  - Clinical Practice Guidelines for Treating Tobacco Use and Dependence advocate for
      using counseling targeted at tobacco users' motivation to quit during each office
      visit. We evaluate tobacco use screening and counseling interventions delivered
      during routine periodic health examinations by 44 adult primary care physicians
      practicing in 22 clinics of a large health system in southeast Michigan. 484
      office visits were audio-recorded and transcribed. For this study, current
      tobacco users (N = 91) were identified using pre-visit surveys and audio
      recordings. Transcripts were coded for the delivery of tobacco-related counseling
      interventions. The extent to which counseling interventions were used and/or
      targeted to the patients' readiness to quit was the main outcome measure. The
      majority of tobacco users (n = 77) had their tobacco use status assessed, and
      most received some sort of tobacco-related counseling (n = 74). However, only 15%
      received the recommended counseling targeted to their readiness to quit. On the
      other hand, 19% received less counseling than recommended given their readiness
      to quit, 7% received only nonindicated counseling, and 59% received nonindicated
      counseling in addition to indicated counseling. Results illustrate physicians'
      commitment to cessation counseling and also identify potential opportunities to
      improve the efficiency of tobacco-related counseling in primary care.

PMID- 26290273
TI  - An injectable drug-loaded hydrogel based on a supramolecular polymeric prodrug.
AB  - We reported a novel injectable doxorubicin-loaded hydrogel based on host-guest
      interaction and Schiff's base reaction. A supramolecular polymeric prodrug was
      prepared through the inclusion of adamantane-modified doxorubicin into the beta
      cyclodextrin cavity on the polyaldehyde dextran chain, which was in situ
      crosslinked by carboxymethyl chitosan. 

PMID- 26290274
TI  - Complications related to sutures following penetrating and deep anterior lamellar
      keratoplasty.

PMID- 26290276
TI  - Improving treatment satisfaction to increase adherence.

PMID- 26290275
TI  - Atenolol vs enalapril in young hypertensive patients after successful repair of
      aortic coarctation.
AB  - Late arterial hypertension has been identified as a major predictor for morbidity
      and mortality in aortic coarctation (AoC) patients. Few data are available about
      efficacy and tolerability of angiotensin converting enzyme inhibitors vs beta
      blockers in young AoC patients. This study aimed to evaluate the tolerability and
      efficacy on 24-h blood pressure (BP) and left ventricular mass/height(2.7)
      (LVMI), of atenolol vs enalapril. We enrolled consecutive AoC hypertensive
      patients with (a) no history of BP treatment or after >48 h of withdrawn, (b)
      aged 6-20 years, (c) body mass index (BMI) <90th percentile for age and sex, (d)
      >12 months from a successful AoC repair and (e) no major associated
      cardiovascular abnormalities. All patient were evaluated with 24-h ambulatory BP
      monitoring, standard echocardiography, strain-strain rate imaging, at enrolment,
      3, 6 and 12 months of treatment. We studied 51 AoC patients (13+/-3.9 years, BMI:
      21.4+/-4.3 kg m(-2)). Patients were randomly assigned at atenolol treatment
      (n=26), or enalapril treatment (n=25). The mean follow-up duration was 11+/-2
      months. Both drugs were able to significantly reduce 24-systolic BP (SBP;
      atenolol: 133+/-11 mm Hg vs 124+/-16 mm Hg, P=0.016; enalapril: 135+/-6 mm Hg vs
      127+/-7 mm Hg, P=0.001). Only enalapril was able to significantly reduce LVMI
      (47+/-12  vs 39.6+/-10 g m(-)(2.7), P=0.016). Only in atenolol group in two cases
      (7.7%) drug withdrawal was needed because of adverse events. Enalapril and
      atenolol are similarly effective in reducing SBP. However, only enalapril
      demonstrated a significant reduction of LVMI. In no case, enalapril was stopped
      because of adverse events.

PMID- 26290277
TI  - Survey to determine the efficacy and safety of guideline-based pharmacological
      therapy for chronic obstructive pulmonary disease patients not previously
      receiving maintenance treatment.
AB  - OBJECTIVE: To investigate the potential beneficial effects of guideline-based
      pharmacological therapy on pulmonary function and quality of life (QOL) in
      Japanese chronic obstructive pulmonary disease (COPD) patients without prior
      treatment. RESEARCH DESIGN AND METHODS: Multicenter survey, open-label study of
      49 Japanese COPD patients aged >= 40 years; outpatients with >10 pack years of
      smoking history; ratio of forced expiratory volume in 1 s (FEV1)/forced vital
      capacity (FVC) < 70%; predicted FEV1 < 80%; treated with bronchodilators and/or
      inhaled corticosteroids as maintenance therapy until week 48. MAIN OUTCOME
      MEASURES: The primary endpoint was change in pulmonary function (trough FEV1,
      trough FVC); secondary endpoints were QOL and physical activity at 48 weeks after
      initiation of therapy. RESULTS: Airway reversibility was confirmed in untreated
      patients. Significant changes over time were not observed for FEV1 and FVC,
      indicating lung function at initiation of treatment was maintained during the
      observation period. COPD assessment test scores showed statistical and clinical
      improvements. Cough, sputum, breathlessness, and shortness of breath were
      significantly improved. CONCLUSIONS: Lung function and QOL of untreated Japanese
      COPD patients improved and improvements were maintained by performing a
      therapeutic intervention that conformed to published guidelines.

PMID- 26290278
TI  - Real-world effectiveness of everolimus-based therapy versus endocrine monotherapy
      and chemotherapy in patients of HR+/HER2- breast cancer with liver metastasis in
      the USA.
AB  - OBJECTIVE: This study investigated the comparative effectiveness of everolimus
      based therapy (EVE) versus endocrine monotherapy (ET) and chemotherapy (CT) in
      the treatment of hormone-receptor-positive human-epidermal-growth-factor-receptor
      2-negative (HR+/HER2-) metastatic breast cancer (mBC) patients with liver
      metastasis. METHODS: Medical charts of patients treated by community oncologists
      were examined. Eligible patients included postmenopausal women with HR+/HER2- mBC
      with liver metastasis who received EVE, ET or CT between 1 July 2012 and 15 April
      2013 after non-steroidal aromatase inhibitor use. Time on treatment (TOT) and
      progression-free survival (PFS) were compared between EVE and ET or CT using
      Kaplan-Meier analyses and Cox proportional hazards models. RESULTS: Among the 202
      patients in the study, 82 received EVE, 49 ET, and 71 CT. After adjusting for
      baseline characteristics, EVE was associated with significantly longer TOT than
      ET (hazard ratio [HR]: 0.49; 95% CI: 0.28 - 0.86) or CT (HR: 0.35; 95% CI: 0.22 -
      0.55), and significantly longer PFS than ET (HR: 0.48; 95% CI: 0.27 - 0.87). PFS
      was not significantly different with EVE versus CT (HR: 0.76; 95% CI: 0.44 -
      1.32). CONCLUSIONS: EVE had significantly longer TOT and PFS than ET and longer
      TOT than CT among postmenopausal HR+/HER2- mBC patients with liver metastasis.

PMID- 26290279
TI  - New pharmacotherapy options for pulmonary arterial hypertension.
AB  - INTRODUCTION: Epoprostenol was the first targeted therapy available for the
      treatment of pulmonary arterial hypertension (PAH). Since then great advances in
      our knowledge of the disease have been made and the spectrum of therapeutic
      options for PAH has expanded. After an overview of current available treatments,
      this article describes the new pharmacotherapy options and their place in the
      management of PAH. AREAS COVERED: This paper is based on a literature search and
      the review of studies published on PAH pharmacotherapy using the MEDLINE
      database. EXPERT OPINION: The last decade has been particularly important in PAH
      management with the emergence of six new molecules, the development of novel
      routes of administration and improvement of pharmacokinetics. Moreover, pediatric
      formulations have been developed. However, further research is required to inform
      clinicians regarding optimal choices of combination therapies (progressive add-on
      therapy or upfront combination therapy, selection of associated molecules
      regarding the patient's profile...), to continue to improve the quality of life
      of patients with new drugs and to reach the ultimate goal of curing the disease.

PMID- 26290280
TI  - Synchronous primary esophageal squamous cell carcinoma and gastric
      adenocarcinoma: analysis of 41 cases treated in a single institution.
AB  - The present study investigated the treatment and survival outcomes of patients
      with synchronous primary esophageal squamous cell carcinoma and gastric
      adenocarcinoma. The medical records of 10,783 patients with primary esophageal
      squamous cancer treated at our institution between 1995 and 2012 were
      retrospectively reviewed. Overall survival (OS) rates were calculated using the
      Kaplan-Meier method. The incidence was 0.38% (41/10,783). Of these 41 patients,
      26 underwent curative surgery, ten received palliative chemotherapy or
      radiotherapy, and five received no treatment. The median OS of the surgery,
      palliative-therapy, and treatment-free groups was 17.1, 9.0, and 3.8 months,
      respectively. The 1-, 3-, 5-, and 10-year OS rates for the surgery group were
      77%, 45%, 33%, and 19%, respectively. No significant differences in median OS
      were observed between the surgery group and the historical cohort of isolated
      esophageal cancer (n = 186) (17.1 vs. 21.0 months, P = 0.061) or isolated gastric
      cancer (n = 51) (17.1 vs. 28.9 months, P = 0.875), or between the palliative
      therapy group and its corresponding historical cohort (n = 30) (9.0 vs. 8.3
      months, P = 0.862). The survival outcomes of patients with synchronous primary
      esophageal squamous and gastric cancers were not worse than those of patients
      with isolated esophageal cancer or isolated gastric cancer. 

PMID- 26290281
TI  - Elevated serum transaminase activities were associated with increased serum
      levels of iron regulatory hormone hepcidin and hyperferritinemia risk.
AB  - Iron imbalance is a feature of liver damage. However, the biological correlation
      of serum hepcidin, a key regulator of iron homeostasis, with liver malfunction is
      undefined. To this end, we piloted the Chinese population studies to address
      whether hepcidin is linked to liver functionality. The serum hepcidin, ferritin,
      alanine transaminase, aspartate transaminase, gamma-glutamyltransferase and
      bilirubin were examined in two independent Chinese cohorts consisted of 3455
      individuals. After adjustment for sex, age, body mass index, smoking habits,
      drinking categories and diabetic status, a positive association between hepcidin
      and alanine transaminase (ALT) (beta = 0.18 +/- 0.01, P < 0.0001) was discovered
      using linear regression in a cohort consisting of 1813 individuals. This
      association was then validated in the second independent cohort of 1642
      individuals (beta = 0.08 +/- 0.02, P < 0.0001). Furthermore, consistent with
      cohort study, by applying both CCl4 and lipopolysaccharide induced mouse liver
      injury models, at least 2-fold elevations in hepcidin expression, serum ALT and
      inflammatory cytokine IL-6 were discovered during the initiation stage of liver
      injury. Our findings suggest that increased serum hepcidin may reflect a
      protective response to the iron status and elevated serum cytokines during liver
      injury. Additional studies are warranted to validate these findings and test
      their potential clinical relevance in patients. 

PMID- 26290282
TI  - Glucagon-like peptide-2 exhibits protective effect on hepatic ischemia
      reperfusion injury in rats.
AB  - Glucagon-like peptide-2 (GLP-2) has potent anti-inflammatory effects and protects
      against experimental ischemia/reperfusion (I/R) injury in pulmonary, intestinal,
      and myocardial tissue. However, its protective abilities against I/R injury in
      the liver are unknown. We investigated the potential role of GLP-2 pretreatment
      on hepatic I/R injury in rats. A total of 24 rats were randomly divided into
      three groups (n = 8). The first group was the control group; the second group was
      the vehicle-treated hepatic ischemia/reperfusion (HIR, vehicle saline-treated)
      group; and the third group was the GLP-2 pretreated I/R (GLP2-IR) group. Each rat
      in the third group was intraperitoneally administered 5 ug GLP-2 for 5 d before
      the procedure. A portal triad was created to induce ischemia with a vascular
      atraumatic clamp. After 40 min, the clamp was released to initiate hepatic
      reperfusion for 6 h. Blood samples and tissue specimens from the liver were
      obtained. Alanine aminotransferase, aspartate aminotransferase, and total
      bilirubin levels significantly increased in the salinetreated HIR group (P <
      0.001), whereas GLP-2 pretreatment significantly decreased their levels (P <
      0.01). Our data suggested that GLP-2 pretreatment may have a protective effect on
      liver I/R injury. However, dose-response studies are necessary to determine the
      most effective dose. 

PMID- 26290285
TI  - Factors related to compliance with oral analgesic treatment of inpatients with
      chronic pain.
AB  - This study aimed to determine the relationship between the different factors of
      analgesic therapy and the compliance of chronic pain inpatients. We prospectively
      investigated 100 consecutive inpatients with noncancer chronic pain who were
      hospitalized to receive oral analgesic treatment in the Pain Department of West
      China Hospital from May 2013 to October 2013. Patients who completed the
      treatment plan were recorded as good compliance, whereas patients who partly
      completed or even refused the treatment were recorded as moderate or non
      compliance, respectively. A total of 73 (73.7%), 17 (17.1%), and 9 (9.2%)
      patients showed good, moderate, and non-compliance, respectively. Univariate
      analyses showed significantly better compliance among farmers, patients educated
      in college or above, with family income of < 3000 CNY, and with severe or
      moderate pain than those employed and unemployed (P = 0.02), patients educated
      below college (P = 0.013), with family income of >= 3000 CNY (P = 0.025), and
      with mild pain (P < 0.001), respectively. Logistic regression analysis showed
      that the family income of >= 3000 CNY (OR: 2.50, 95%CI: 1.65-4.51, P = 0.021) and
      mild pain (OR: 1.27, 95%CI: 1.03-3.31, P = 0.016) were associated with moderate
      or non-compliance with oral analgesic treatment. In conclusion, the low
      compliance with oral treatment of analgesics was found in Chinese inpatients with
      chronic pain and compliance was negatively associated with family income and
      degree of pain of patients. 

PMID- 26290283
TI  - Environmental pollution and DNA methylation: carcinogenesis, clinical
      significance, and practical applications.
AB  - Environmental pollution is one of the main causes of human cancer. Exposures to
      environmental carcinogens result in genetic and epigenetic alterations which
      induce cell transformation. Epigenetic changes caused by environmental pollution
      play important roles in the development and progression of environmental
      pollution-related cancers. Studies on DNA methylation are among the earliest and
      most conducted epigenetic research linked to cancer. In this review, the roles of
      DNA methylation in carcinogenesis and their significance in clinical medicine
      were summarized, and the effects of environmental pollutants, particularly air
      pollutants, on DNA methylation were introduced. Furthermore, prospective
      applications of DNA methylation to environmental pollution detection and cancer
      prevention were discussed. 

PMID- 26290286
TI  - Systematic review: instruments to assess abdominal pain in irritable bowel
      syndrome.
AB  - BACKGROUND: Consensus on standard methods to assess chronic abdominal pain in
      patients with irritable bowel syndrome (IBS) is currently lacking. AIM: To
      systematically review the literature with respect to instruments of measurement
      of chronic abdominal pain in IBS patients. METHODS: Systematic literature search
      was performed in PubMed/Medline databases for studies using pain measurement
      instruments in patients with IBS. RESULTS: One hundred and ten publications were
      reviewed. A multitude of different instruments is currently used to assess
      chronic abdominal pain in IBS patients. The single-item methods, e.g. the
      validated 10-point numeric rating scale (NRS), and questionnaires assessing
      gastrointestinal symptoms severity, focus mostly on the assessment of only the
      intensity of abdominal pain. Of these questionnaires, the validated IBS-Symptom
      Severity Scale includes the broadest measurement of pain-related aspects. General
      pain questionnaires and electronic momentary symptom assessment tools have been
      used to study abdominal pain in IBS patients, but have not yet been validated for
      this purpose. The evidence for the use of provocation tests, e.g. the rectal
      barostat with balloon distention, for measurement of abdominal pain in IBS is
      weak, due to the poor correlation between visceral pain thresholds assessed by
      provocation tests and abdominal pain as assessed by retrospective questionnaires.
      CONCLUSIONS: The multitude of different instruments to measure chronic abdominal
      pain in IBS makes it difficult to compare endpoints of published studies. There
      is need for validated instruments to assess chronic abdominal pain in IBS
      patients, that overcome the limitations of the currently available methods.

PMID- 26290284
TI  - Molecular mechanisms of fatty liver in obesity.
AB  - Nonalcoholic fatty liver disease (NAFLD) covers a spectrum of liver disorders
      ranging from simple steatosis to advanced pathologies, including nonalcoholic
      steatohepatitis and cirrhosis. NAFLD significantly contributes to morbidity and
      mortality in developed societies. Insulin resistance associated with central
      obesity is the major cause of hepatic steatosis, which is characterized by
      excessive accumulation of triglyceride-rich lipid droplets in the liver.
      Accumulating evidence supports that dysregulation of adipose lipolysis and liver
      de novo lipogenesis (DNL) plays a key role in driving hepatic steatosis. In this
      work, we reviewed the molecular mechanisms responsible for enhanced adipose
      lipolysis and increased hepatic DNL that lead to hepatic lipid accumulation in
      the context of obesity. Delineation of these mechanisms holds promise for
      developing novel avenues against NAFLD. 

PMID- 26290287
TI  - Dps from Deinococcus radiodurans: oligomeric forms of Dps1 with distinct cellular
      functions and Dps2 involved in metal storage.
AB  - The DNA binding proteins from starved cells from Deinococcus radiodurans, Dps1
      DR2263 and Dps2-DRB0092, have a common overall structure of hollow spherical
      dodecamers. Their involvement in the homeostasis of intracellular metal and DNA
      protection was addressed. Our results show that DrDps proteins are able to
      oxidize ferrous to ferric iron by oxygen or hydrogen peroxide. The iron stored
      inside the hollow sphere cavity is fully released. Furthermore, these proteins
      are able to store and release manganese, suggesting they can play a role in
      manganese homeostasis as well. The interaction of DrDps with DNA was also
      addressed. Even though DrDps1 binds both linear and coiled DNA, DrDps2
      preferentially binds to coiled DNA, forming different protein-DNA complexes, as
      clearly shown by atomic force microscopy. DrDps1 (dimer and dodecamer) and DrDps2
      can protect DNA against reactive oxygen species, although the protection occurs
      at different Fe to protein ratios. The difference between DrDps could be the
      result of the DrDps1 higher iron oxidation rate in the presence of hydrogen
      peroxide and its higher affinity to bind DNA than in DrDps2. Using cellular
      extracts obtained from D. radiodurans cultures, we showed that DrDps1 oligomers
      observed in in vitro conditions are also present in vivo. This indicates that
      DrDps1 has a structural dynamic plasticity that allows its oligomeric state to
      change between dimer, trimer and dodecamer. This in turn suggests the existence
      of a regulation mechanism that modulates the oligomer equilibrium and is
      dependent on growth stages and environmental conditions.

PMID- 26290288
TI  - Varicocele: the origin of benign prostatic hypertrophy? Testosterone dosages in
      the periprostatic plexus.
AB  - OBJECTIVES: In 2008, Gat et al. wrote the hypothesis that benign prostatic
      hypertrophy (BPH) was caused by reflux from high free testosterone containing
      blood from varicocele. The purpose of this study is to measure testosterone at
      the prostatic veins in patients operated for large BPH, confirming Gat's theory.
      MATERIAL AND METHODS: In 13 patients, operated by Millin technique, the
      periprostatic plexus was punctured in 45 degrees  tilted position in order to the
      measure total and free testosterone and dihydrotestosterone. Brachial blood was
      taken simultaneously for similar measurements. Seven patients had a clinical
      varicocele. RESULTS: High testosterone levels, in comparison with the brachial
      blood, were detected in only two patients. Dihydrotestosterone was at least
      doubled in all cases, demonstrating that the puncture was done in prostatic
      drainage area. CONCLUSION: Gat's theory, concerning the role of varicocele in the
      origin of BPH, could not be confirmed in this study. Technical limitations can be
      responsible for this.

PMID- 26290289
TI  - FROM TALK TO ACTION: POLICY STAKEHOLDERS, APPROPRIATENESS, AND SELECTIVE
      DISINVESTMENT.
AB  - OBJECTIVES: There is widespread commitment--at least in principle--to "evidence
      informed" clinical practice and policy development in health care. The intention
      is that only "appropriate" care ought to be delivered at public expense. Although
      the rationale for an appropriateness agenda is widely endorsed, and methods have
      been proposed for addressing it, few published studies exist of contemporary
      policy initiatives which have actually led to successful disinvestment. Our
      objective was to explore whether the direct involvement of policy stakeholders
      could advance appropriateness and disinvestment. METHODS: Several collaborative
      engagements with policy stakeholders were undertaken to adapt and combine
      conceptual and empirical material related to appropriateness and disinvestment
      from the literature to create tools and processes for use in Canada and the
      province of Ontario in particular. RESULTS: By combining inputs from the
      literature with colloquial evidence from policy stakeholders, a definition of
      appropriateness was developed and, importantly, endorsed by all the provincial
      and territorial ministers of health in Canada. Second, a reassessment framework
      was successfully implemented for identifying priorities for selective
      disinvestment. CONCLUSIONS: When scientific evidence was combined with colloquial
      evidence from policy stakeholders, progress was made on the design and successful
      implementation of policies for appropriateness and disinvestment.

PMID- 26290290
TI  - Discovery of Novel 15-Lipoxygenase Activators To Shift the Human Arachidonic Acid
      Metabolic Network toward Inflammation Resolution.
AB  - For disease network intervention, up-regulating enzyme activities is equally as
      important as down-regulating activities. However, the design of enzyme activators
      presents a challenging route for drug discovery. Previous studies have suggested
      that activating 15-lipoxygenase (15-LOX) is a promising strategy to intervene the
      arachidonic acid (AA) metabolite network and control inflammation. To prove this
      concept, we used a computational approach to discover a previously unknown
      allosteric site on 15-LOX. Both allosteric inhibitors and novel activators were
      discovered using this site. The influence of activating 15-LOX on the AA
      metabolite network was then investigated experimentally. The activator was found
      to increase levels of 15-LOX products and reduce production of pro-inflammatory
      mediators in human whole blood assays. These results demonstrate the promising
      therapeutic value of enzyme activators and aid in further development of
      activators of other proteins.

PMID- 26290291
TI  - Introduction to the European Hydration Institute's Expert Conference on Human
      Hydration, Health, and Performance.

PMID- 26290292
TI  - Fate of ingested fluids: factors affecting gastric emptying and intestinal
      absorption of beverages in humans.
AB  - The volume of fluid ingested for rehydration is essential in determining the
      restoration of euhydration because it must be in excess of the water lost since
      the individual was last euhydrated. The formulation of any ingested beverage is
      also important as this affects the rate at which the fluid is emptied from the
      stomach, absorbed in the small intestine, and hence assimilated into the body
      water pool. This review highlights the essential role of the gastrointestinal
      tract in the maintenance of hydration status. 

PMID- 26290293
TI  - Determinants of water and sodium intake and output.
AB  - Physiological regulation of sodium and water intake and output is required for
      the maintenance of homeostasis. The behavioral and neuroendocrine mechanisms that
      govern fluid and salt balance are highly interdependent, with acute and chronic
      alterations in renal output tightly balanced by appropriate changes in thirst
      and, to a lesser extent in humans, sodium appetite. In healthy individuals, these
      tightly coupled mechanisms maintain extracellular fluid volume and body tonicity
      within a narrow homeostatic range by initiating ingestive behaviors and the
      release of hormones necessary to conserve water and sodium within the body. In
      this review, the factors that determine output of sodium and fluid and those that
      determine "normal" input (i.e., matched to output) are addressed. For output,
      individual variability accompanied by dysregulation of homeostatic mechanisms may
      contribute to acute and/or chronic disease. To illustrate that point, the
      specific condition of salt-sensitive hypertension is discussed. For input,
      physical characteristics, physiological phenotypes, genetic and developmental
      influences, and cultural and environmental factors combine to result in a wide
      range of individual variability that, in humans, is compensated for by
      alterations in excretion. 

PMID- 26290294
TI  - Do small differences in hydration status affect mood and mental performance?
AB  - Although it has been suggested that many in the general population are dehydrated
      to the extent that mood and cognition are disrupted, there has been little
      research investigating mild levels of dehydration. When dehydration reduces body
      mass by more than 2%, it has been consistently reported that mood is influenced,
      fatigue is greater, and alertness is lower. In contrast, the effects on cognition
      have been less consistent. Only a few studies have looked at females and these
      studies made little attempt to consider hormones that influence kidney
      functioning. In particular, there has been virtually no attempt to look at
      changes in hydration status in the range that occurs in individuals with a
      sedentary lifestyle in a temperate climate. There is a consequent need to study
      individuals who have lost up to 1% of body mass due to dehydration. While 4
      intervention trials have found that the cognition of children improved in
      response to water consumption, the effects of water consumption on cognition in
      older adults, another high-risk group, have been largely ignored. 

PMID- 26290295
TI  - Acute and chronic effects of hydration status on health.
AB  - Maintenance of fluid and electrolyte balance is essential to healthy living as
      dehydration and fluid overload are associated with morbidity and mortality. This
      review presents the current evidence for the impact of hydration status on
      health. The Web of Science, MEDLINE, PubMed, and Google Scholar databases were
      searched using relevant terms. Randomized controlled trials and large cohort
      studies published during the 20 years preceding February 2014 were selected.
      Older articles were included if the topic was not covered by more recent work.
      Studies show an association between hydration status and disease. However, in
      many cases, there is insufficient or inconsistent evidence to draw firm
      conclusions. Dehydration has been linked with urological, gastrointestinal,
      circulatory, and neurological disorders. Fluid overload has been linked with
      cardiopulmonary disorders, hyponatremia, edema, gastrointestinal dysfunction, and
      postoperative complications. There is a growing body of evidence that links
      states of fluid imbalance and disease. However, in some cases, the evidence is
      largely associative and lacks consistency, and the number of randomized trials is
      limited. 

PMID- 26290296
TI  - Effects of acute and chronic hypohydration on kidney health and function.
AB  - The kidneys play a critical role in the homeostasis of body fluid tonicity and
      effective circulating volume. Renal homeostatic mechanisms are frequently
      challenged in acutely ill people. Fluid depletion causing hypovolemia may result
      in renal hypoperfusion that, if left untreated, may lead to acute kidney failure.
      Some populations, notably older people and neonates, are less tolerant of
      extremes in fluid loading and deprivation, similar to those with established
      chronic kidney disease. Risk of kidney injury during fluid depletion is increased
      by medications including diuretics, nonsteroidal antiinflammatory drugs, and
      renin-angiotensin system blockers. There is no consistent evidence indicating
      that lower-than-average fluid intake can cause chronic kidney disease, nor
      accelerate progression of established kidney disease. Increasing consumption of
      sugar-containing beverages is, however, a major concern for kidney health as a
      precursor of obesity and diabetes. There is no evidence that high dietary protein
      intake can cause chronic kidney disease, nor accelerate progression of
      established kidney disease. Idiosyncratic, adverse renal responses have been
      described with creatine supplements. There are only a few clinical conditions for
      which high fluid intake should be considered. These include recurrent kidney
      stones or urinary tract infections and, possibly, polycystic kidney disease. 

PMID- 26290297
TI  - Impact of beverage intake on metabolic and cardiovascular health.
AB  - This review is based on a presentation that was made at a meeting concerning
      hydration. It summarizes the epidemiological evidence for selected beverages in
      relation to cardiovascular and/or metabolic health. The review focuses on tea,
      cocoa, milk, orange juice, alcohol, and beverages sweetened with sugars. These
      beverage types were chosen because of their widespread consumption, with tea,
      cocoa, orange juice, and milk being of potential benefit while alcohol and sugars
      may be detrimental. There is reasonably consistent evidence of reduced risk of
      cardiovascular disease (CVD) in association with high consumption of tea, with
      the tea flavonoids appearing to be responsible for these benefits. There is also
      a growing evidence base for cocoa flavanols to have beneficial cardiovascular
      effects. The bulk of the evidence supporting these conclusions is epidemiological
      and needs to be confirmed with randomized controlled trials. Milk is associated
      with reduced risk of CVD, particularly in relation to blood pressure, with
      certain milk tripeptides being implicated in having effects to reduce angiotensin
      action. Further work is needed to confirm these potentially beneficial effects.
      There is some evidence of potentially beneficial effects of orange juice on
      aspects of cardiovascular function, but this is by no means convincing, and
      further evidence is needed from randomized controlled trials, together with the
      elucidation of whether any benefits are linked to the citrus flavanones or simply
      to the vitamin C content. While there is some evidence that red wine may convey
      some health benefits, there is also clear evidence that alcoholic beverages can
      have undesirable effects on blood pressure and increase the risk of CVD. It is
      possible that low to moderate intakes of alcoholic beverages may be beneficial.
      There is some evidence that beverages sweetened with sugars may contribute to
      increased energy intake and weight gain, and there is also an indication from
      longitudinal cohort studies that they are associated with an increased risk of
      developing type 2 diabetes. The mechanism of this latter association has not been
      explained. In conclusion, there is a substantial amount of epidemiological
      evidence for benefits of tea and cocoa in relation to cardiovascular health.
      There is a growing literature describing randomized controlled trials, but more
      evidence is needed. Potential cardiovascular and metabolic health benefits of
      milk and orange juice needs further investigation. The associations of higher
      alcohol intakes and consumption of beverages sweetened with sugars and their
      increased health risks are of concern, and more attention should be focused on
      this area. 

PMID- 26290298
TI  - Implications of active lifestyles and environmental factors for water needs and
      consequences of failure to meet those needs.
AB  - Heat stress and exercise increase water loss from the body, primarily in the form
      of sweat. For some occupational groups, including miners, construction workers in
      hot climates, soldiers, and some athletes, daily water losses can reach 10-12 L.
      These losses must be replaced on a daily basis to maintain functional capacity.
      Both hyperhydration and hypohydration will, if sufficiently severe, impair all
      aspects of physiological function. Tests of strength and power are largely
      unaffected by dehydration of up to about 2%-4% of body mass. However, decrements
      in the performance of endurance tests may occur at these levels, especially in
      warm environments. Body water deficits, if sufficiently severe, also have adverse
      effects on measures of mood and on some elements of cognitive function and result
      in an increased subjective rating of the perception of effort. Beverages consumed
      during exercise can provide carbohydrates and electrolytes that may be beneficial
      in some situations; however, drinking in volumes required to match sweat loss may
      cause gastrointestinal discomfort that will generally impair performance. 

PMID- 26290299
TI  - Patterns of drinking and eating across the European Union: implications for
      hydration status.
AB  - Appropriate hydration is essential for health and well-being. In Europe, water
      consumption patterns vary despite the unlimited availability of this resource.
      Water constitutes the largest proportion of total fluid intake in most countries.
      According to the 2008 European Food Safety Authority's Concise Food Consumption
      Database, tap water consumption was highest in the northern European countries
      and in Austria. While Germany had a particularly low intake of tap water, it led
      in consumption of fruit and vegetable juices, soft drinks, and especially bottled
      water. European nutrition surveys generally report an average fluid intake within
      the recommended range of 1500-2000 mL/day, with higher intake levels
      corresponding with increasing frequency of intake. However, some population
      groups consume less than others, e.g., the elderly who are at higher risk for
      dehydration due to age-related increased urinary fluid losses. In turn, physical
      activity is associated with higher beverage consumption as is adherence to a
      health-conscious diet. While water constitutes the most commonly consumed
      beverage throughout Europe, drinking patterns and quantities vary and are
      influenced by a variety of factors, including age, gender, diet, and physical
      activity level. 

PMID- 26290304
TI  - Heinrich Noth (1928-2015).

PMID- 26290300
TI  - Executive summary and conclusions from the European Hydration Institute Expert
      Conference on human hydration, health, and performance.
AB  - On April 7-8, 2014, the European Hydration Institute hosted a small group of
      experts at Castle Combe Manor House, United Kingdom, to discuss a range of issues
      related to human hydration, health, and performance. The meeting included 18
      recognized experts who brought a wealth of experience and knowledge to the topics
      under review. Eight selected topics were addressed, with the key issues being
      briefly presented before an in-depth discussion. Presented here is the executive
      summary and conclusions from this meeting. 

PMID- 26290307
TI  - Conversations about care.

PMID- 26290306
TI  - Reassessment of the risk factors for biochemical recurrence in D'Amico
      intermediate-risk prostate cancer treated using radical prostatectomy.
AB  - OBJECTIVES: To assess the risk factors for biochemical recurrence in D'Amico
      intermediate-risk prostate cancer patients treated using radical prostatectomy.
      METHODS: We retrospectively reviewed the medical records of 1268 men with
      prostate cancer treated using radical prostatectomy without neoadjuvant therapy.
      The association between various risk factors and biochemical recurrence was then
      statistically evaluated. The Kaplan-Meier method, log-rank tests and Cox
      proportional hazards models were used for statistical analysis. RESULTS: In the
      intermediate-risk group, 96 patients (14.5%) experienced biochemical recurrence
      during a median follow up of 41 months. In the intermediate-risk group,
      preoperative prostate-specific antigen level, prostate volume and prostate
      specific antigen density were significant preoperative risk factors for
      biochemical recurrence, whereas other factors including age, primary Gleason 4,
      clinical stage >T2 and percentage of positive biopsies were not. In multivariate
      analysis, higher preoperative prostate-specific antigen level and density, and a
      smaller prostate volume were independent risk factors for biochemical recurrence
      in the intermediate-risk group. Biochemical recurrence-free survival of patients
      in the intermediate-risk group with a higher prostate-specific antigen level and
      density (>=15 ng/mL, >=0.6 ng/mL/cm(3), respectively), and lower prostate volume
      (<=10 mL) was comparable with that of high-risk group individuals (P = 0.632,
      0.494 and 0.961, respectively). CONCLUSIONS: Preoperative prostate-specific
      antigen, prostate volume and prostate-specific antigen density are significant
      risk factors for biochemical recurrence in D'Amico intermediate-risk prostate
      cancer patients treated using radical prostatectomy. Using these variables, a
      subset of the intermediate-risk patients can be identified as having equivalent
      outcomes to high-risk patients.

PMID- 26290308
TI  - Student perspectives on: Does nursing have a future?

PMID- 26290311
TI  - Genetic Basis of Differential Heat Resistance between Two Species of Congeneric
      Freshwater Snails: Insights from Quantitative Proteomics and Base Substitution
      Rate Analysis.
AB  - We compared the heat tolerance, proteomic responses to heat stress, and adaptive
      sequence divergence in the invasive snail Pomacea canaliculata and its
      noninvasive congener Pomacea diffusa. The LT50 of P. canaliculata was
      significantly higher than that of P. diffusa. More than 3350 proteins were
      identified from the hepatopancreas of the snails exposed to acute and chronic
      thermal stress using iTRAQ-coupled mass spectrometry. Acute exposure (3 h
      exposure at 37  degrees C with 25  degrees C as control) resulted in similar
      numbers (27 in P. canaliculata and 23 in P. diffusa) of differentially expressed
      proteins in the two species. Chronic exposure (3 weeks of exposure at 35  degrees
      C with 25  degrees C as control) caused differential expression of more proteins
      (58 in P. canaliculata and 118 in P. diffusa), with many of them related to
      restoration of damaged molecules, ubiquitinating dysfunctional molecules, and
      utilization of energy reserves in both species; but only in P. diffusa was there
      a shift from carbohydrate to lipid catabolism. Analysis of orthologous genes
      encoding the differentially expressed proteins revealed two genes having clear
      evidence of positive selection (Ka/Ks > 1) and seven candidates for more detailed
      analysis of positive selection (Ka/Ks between 0.5 and 1). These nine genes are
      related to energy metabolism, cellular oxidative homeostasis, signaling, and
      binding processes. Overall, the proteomic and base substitution rate analyses
      indicate genetic basis of differential resistance to heat stress between the two
      species, and such differences could affect their further range expansion in a
      warming climate. 

PMID- 26290312
TI  - Ankle antagonist coactivation in the double-support phase of walking: Stroke vs.
      healthy subjects.
AB  - INTRODUCTION: Lesions in ipsilateral systems related to postural control in the
      ipsilesional side may justify the lower performance of stroke subjects during
      walking. PURPOSE: To analyze bilateral ankle antagonist coactivation during
      double support in stroke subjects. METHODS: Sixteen (8 females; 8 males) subjects
      with a first isquemic stroke and 22 controls (12 females; 10 males) participated
      in this study. The double-support phase was assessed through ground reaction
      forces and the electromyography of ankle muscles was assessed in both limbs.
      RESULTS: The ipsilesional limb presented statistically significant differences
      from the control when assuming specific roles during double support. The tibialis
      anterior and soleus pair was the one in which this atypical behavior was more
      pronounced. CONCLUSION: The ipsilesional limb presents a dysfunctional behavior
      when a higher postural control activity was demanded.

PMID- 26290313
TI  - Amelanotic melanoma in albinism: the power of dermatoscopy.

PMID- 26290314
TI  - Groundwater Contamination Due to Activities of an Intensive Hog Farming Operation
      Located on a Geologic Fault in East Mediterranean: A Study on COD, BOD5 and
      Microbial Load.
AB  - The application of treated animal wastewater produced in intensive fog farming
      operations (IHFOs) on surface soil, leads to groundwater contamination. In this
      study, the contamination of a Mediterranean aquifer caused by long-term
      application of treated wastewater, produced by an IHFO, on a plot with a geologic
      fault within the IHFO boundaries, was investigated. Groundwater samples were
      taken from monitoring wells close to the IHFO. A significant increase of chemical
      oxygen demand (COD), biochemical oxygen demand (BOD5), total viable count (TVC)
      and total coliform (TC) concentrations was found in wells, compared to control
      monitoring well, which were mainly affected by the subsurface flow of
      contaminated water, due to the presence of the geologic fault. During the winter,
      significant increases in concentrations of COD, BOD5, TVC and TC were noted and
      attributed to increased precipitation, which assisted in the accelerated
      transport of organic compounds and microbial load, through geologic fault, to
      groundwater.

PMID- 26290315
TI  - Understanding the processes governing performance and durability of solid oxide
      electrolysis cells.
AB  - Operation of a Ni-YSZ electrode supported Solid Oxide Cell (SOC) was studied in
      both fuel cell mode (FC-mode) and electrolysis cell mode (EC-mode) in mixtures of
      H2O/H2, CO2/CO, H2O/H2O/CO2/CO at 750  degrees C, 800  degrees C and 850  degrees
      C. Although the SOCs are reversible, the polarisation characterisation shows that
      the kinetics for the reduction of H2O and CO2 is slower compared to oxidation of
      H2 and CO, and that oxidation/reduction in CO2/CO mixtures is slower than in
      H2O/H2 mixtures. The kinetic differences are partly related to the polarisation
      heating and the entropy change. Also the diffusion resistance is larger in EC
      mode as compared to FC-mode and the low frequency concentration resistance (which
      is affected by diffusion), is asymmetric around the open circuit voltage (OCV),
      and is significantly higher in the EC-mode. Both the increased diffusion
      resistance and the asymmetric low frequency concentration resistance result in a
      decreased activity in the EC-mode. Changing the porosity of the support structure
      shows a significant change in both the diffusion resistance and low frequency
      concentration resistance when applying current, showing that diffusion
      limitations cannot be neglected for SOCs operated in the EC-mode. Also the Ni-YSZ
      TPB resistance is affected by changing the support porosity, indicating that
      kinetic investigations under current and even at OCV, and the chase for a general
      expression for "all" Ni-YSZ electrodes may be pointless. The diffusion
      limitations through the support and active electrode structure create an
      increased reducing atmosphere at the interface which may be related to the
      degradation of the cells. 

PMID- 26290317
TI  - One-step reconstruction with a 3D-printed, biomechanically evaluated custom
      implant after complex pelvic tumor resection.
AB  - Resection of a pelvic tumor is challenging because of its complex three
      dimensional (3D) anatomy and deep-seated location with nearby vital structures.
      The resection is technically demanding if a custom implant is used for
      reconstruction of the bone defect as the surgeon needs to ensure the resection
      margin is sufficiently wide and the orientation of intended resection planes must
      match that of the custom implant. We describe a novel workflow of performing a
      partial acetabular resection in a patient with pelvic chondrosarcoma and
      reconstruction with a custom pelvic implant in a one-step operation. A multi
      planar bone resection was virtually planned. A computer-aided design implant that
      both matched the bone defect and biomechanically evaluated was prefabricated with
      3D printing technology. The 3D-printed patient-specific instruments (PSIs) were
      used to reproduce the same planned resection. The histology of the tumor specimen
      showed a clear resection margin. The errors of the achieved resection and implant
      position were deviating (1-4 mm) from the planned. The patient could walk unaided
      with a good hip function. No tumor recurrence and implant loosening were noted at
      11 months after surgery. The use of this novel CT-based method for surgical
      planning, the engineering software for implant design and validation, together
      with 3D printing technology for implant and PSI fabrication makes it possible to
      generate a personalized, biomechanically evaluated implant for accurate
      reconstruction after a pelvic tumor resection in a one-step operation. Further
      study in a larger population is needed to assess the clinical efficacy of the
      workflow in complex bone tumor surgery. 

PMID- 26290316
TI  - An epistatic effect of apaf-1 and caspase-9 on chlamydial infection.
AB  - Chlamydia is an obligate intracellular bacterial pathogen that replicates solely
      within a membrane-bound vacuole termed an inclusion. Chlamydia seems to perturb
      multiple cellular processes of the host, such as, rearrangement of the membrane
      trafficking system for its intracellular multiplication, and inhibition of host
      cell apoptosis for persistent infection. In an attempt to clarify host factor
      involvement in apoptosis regulation, we found that inhibition of Caspase-9
      restricted, while Apaf-1 promoted, Chlamydia pneumoniae infection in HEp-2, HeLa,
      and mouse epithelial fibroblast (MEF) cells. These opposition contributions to
      the chlamydial infection were confirmed using caspase-9 (-/-) and apaf-1 (-/-)
      MEFs. Similar phenomena also appeared in the case of infection with Chlamydia
      trachomatis. Interestingly, caspase-9 in apaf-1 (-/-) MEFs was activated by
      chlamydial infection but during the infection caspase-3 was not activated. That
      is, caspase-9 was activated without support for multiplication and activation by
      Apaf-1, and the activated caspase-9 may be physically disconnected from the
      caspase cascade. This may be partially explained by the observation of caspase-9
      accumulation within chlamydial inclusions. The sequestration of caspase-9 by
      chlamydia seems to result in apoptosis repression, which is crucial for the
      chlamydial development cycle. Because Apaf-1 shares domains with intracellular
      innate immune receptor NOD1, it may play a key role in the strategy to regulate
      chlamydial infection. 

PMID- 26290319
TI  - Who will deliver personalized medicine?

PMID- 26290320
TI  - Single-shot spectro-temporal characterization of XUV pulses from a seeded free
      electron laser.
AB  - Intense ultrashort X-ray pulses produced by modern free-electron lasers (FELs)
      allow one to probe biological systems, inorganic materials and molecular reaction
      dynamics with nanoscale spatial and femtoscale temporal resolution. These
      experiments require the knowledge, and possibly the control, of the spectro
      temporal content of individual pulses. FELs relying on seeding have the potential
      to produce spatially and temporally fully coherent pulses. Here we propose and
      implement an interferometric method, which allows us to carry out the first
      complete single-shot spectro-temporal characterization of the pulses, generated
      by an FEL in the extreme ultraviolet spectral range. Moreover, we provide the
      first direct evidence of the temporal coherence of a seeded FEL working in the
      extreme ultraviolet spectral range and show the way to control the light
      generation process to produce Fourier-limited pulses. Experiments are carried out
      at the FERMI FEL in Trieste. 

PMID- 26290321
TI  - The best and worst treatments for Helicobacter pylori.

PMID- 26290322
TI  - (1)H and (13)C NMR assignments of sesquiterpenes from Dysidea fragilis.

PMID- 26290323
TI  - The effect of concentrated bone marrow aspirate in operative treatment of fifth
      metatarsal stress fractures; a double-blind randomized controlled trial.
AB  - BACKGROUND: Fifth metatarsal (MT-V) stress fractures often exhibit delayed union
      and are high-risk fractures for non-union. Surgical treatment, currently
      considered as the gold standard, does not give optimal results, with a mean time
      to fracture union of 12-18 weeks. In recent studies, the use of bone marrow cells
      has been introduced to accelerate healing of fractures with union problems. The
      aim of this randomized trial is to determine if operative treatment of MT-V
      stress fractures with use of concentrated blood and bone marrow aspirate (cB +
      cBMA) is more effective than surgery alone. We hypothesize that using cB + cBMA
      in the operative treatment of MT-V stress fractures will lead to an earlier
      fracture union. METHODS/DESIGN: A prospective, double-blind, randomized
      controlled trial (RCT) will be conducted in an academic medical center in the
      Netherlands. Ethics approval is received. 50 patients will be randomized to
      either operative treatment with cB + cBMA, harvested from the iliac crest, or
      operative treatment without cB + cBMA but with a sham-treatment of the iliac
      crest. The fracture fixation is the same in both groups, as is the post-operative
      care.. Follow up will be one year. The primary outcome measure is time to union
      in weeks on X-ray. Secondary outcome measures are time to resumption of work and
      sports, functional outcomes (SF-36, FAOS, FAAM), complication rate, composition
      of osteoprogenitors in cB + cBMA and cost-effectiveness. Furthermore, a bone
      biopsy is taken from every stress fracture and analysed histologically to
      determine the stage of the stress fracture. The difference in primary endpoint
      between the two groups is analysed using student's t-test or equivalent.
      DISCUSSION: This trial will likely provide level-I evidence on the effectiveness
      of cB + cBMA in the operative treatment of MT-V stress fractures. TRIAL
      REGISTRATION: Netherlands Trial Register (reg.nr NTR4377 ).

PMID- 26290324
TI  - Radiofrequency thermo-ablation of PVNS in the knee: initial results.
AB  - INTRODUCTION: Pigmented villonodular synovitis (PVNS) is normally treated by
      arthroscopic or open surgical excision. We present our initial experience with
      radiofrequency thermo-ablation (RF ablation) of PVNS located in an inaccessible
      location in the knee. MATERIALS: Review of all patients with histologically
      proven PVNS treated with RF ablation and with at least 2-year follow-up. RESULTS:
      Three patients met inclusion criteria and were treated with RF ablation. Two of
      the patients were treated successfully by one ablation procedure. One of the
      three patients had a recurrence which was also treated successfully by repeat RF
      ablation. There were no complications and all patients returned to their previous
      occupations following RF ablation. CONCLUSION: In this study we demonstrated the
      feasibility of performing RF ablation to treat PVNS in relatively inaccessible
      locations with curative intent. We have also discussed various post-ablation
      imaging appearances which can confound the assessment for residual/recurrent
      disease.

PMID- 26290325
TI  - Femoral condyle insufficiency fractures: associated clinical and morphological
      findings and impact on outcome.
AB  - OBJECTIVE: To determine the characteristics of femoral condyle insufficiency
      fracture (FCIF) lesions and their relative associations with the risk of clinical
      progression. MATERIALS AND METHODS: This HIPAA-compliant retrospective study was
      approved by our Institutional Review Board. Seventy-three patients (age range, 19
      95) were included after excluding patients with post-traumatic fractures, bone
      marrow infarct, osteochondritis dissecans, or underlying tumor. Two board
      certified musculoskeletal radiologists classified morphologic findings including
      lesion diameter, associated bone marrow edema pattern, and associated
      cartilage/meniscus damage. Electronic medical charts were evaluated for symptoms,
      risk factors, and longitudinal outcomes, including total knee arthroplasty (TKA).
      Imaging characteristics were correlated with clinical findings, and comparison of
      outcome groups was performed using a regression model adjusted for age. RESULTS:
      The majority of patients with FCIF were women (64.4%, 47/73), on average 10 years
      older than men (66.28 +/- 15.86 years vs. 56.54 +/- 10.39 years, p = 0.005). The
      most common location for FCIF was the central weight-bearing surface of the
      medial femoral condyle; overlying full thickness cartilage loss (75.7%, 53/70)
      and ipsilateral meniscal injury (94.1%, 64/68) were frequently associated.
      Clinical outcomes were variable, with 23.9% (11/46) requiring TKA. Cartilage
      WORMS score, adjacent cartilage loss, and contralateral meniscal injury, in
      addition to decreased knee range of motion at presentation, were significantly
      associated with progression to TKA (p < 0.05). CONCLUSIONS: FCIF are frequently
      associated with overlying cartilage loss and ipsilateral meniscal injury. The
      extent of cartilage loss and meniscal damage, in addition to loss of knee range
      of motion at the time of presentation, are significantly associated with clinical
      progression.

PMID- 26290327
TI  - Review and Evaluation of Mindfulness-Based iPhone Apps.
AB  - BACKGROUND: There is growing evidence for the positive impact of mindfulness on
      wellbeing. Mindfulness-based mobile apps may have potential as an alternative
      delivery medium for training. While there are hundreds of such apps, there is
      little information on their quality. OBJECTIVE: This study aimed to conduct a
      systematic review of mindfulness-based iPhone mobile apps and to evaluate their
      quality using a recently-developed expert rating scale, the Mobile Application
      Rating Scale (MARS). It also aimed to describe features of selected high-quality
      mindfulness apps. METHODS: A search for "mindfulness" was conducted in iTunes and
      Google Apps Marketplace. Apps that provided mindfulness training and education
      were included. Those containing only reminders, timers or guided meditation
      tracks were excluded. An expert rater reviewed and rated app quality using the
      MARS engagement, functionality, visual aesthetics, information quality and
      subjective quality subscales. A second rater provided MARS ratings on 30% of the
      apps for inter-rater reliability purposes. RESULTS: The "mindfulness" search
      identified 700 apps. However, 94 were duplicates, 6 were not accessible and 40
      were not in English. Of the remaining 560, 23 apps met inclusion criteria and
      were reviewed. The median MARS score was 3.2 (out of 5.0), which exceeded the
      minimum acceptable score (3.0). The Headspace app had the highest average score
      (4.0), followed by Smiling Mind (3.7), iMindfulness (3.5) and Mindfulness Daily
      (3.5). There was a high level of inter-rater reliability between the two MARS
      raters. CONCLUSIONS: Though many apps claim to be mindfulness-related, most were
      guided meditation apps, timers, or reminders. Very few had high ratings on the
      MARS subscales of visual aesthetics, engagement, functionality or information
      quality. Little evidence is available on the efficacy of the apps in developing
      mindfulness.

PMID- 26290326
TI  - Polymorphisms in GCKR, SLC17A1 and SLC22A12 were associated with phenotype gout
      in Han Chinese males: a case-control study.
AB  - BACKGROUND: Gout is a common arthritic disease resulting from elevated serum uric
      acid (SUA) level. A large meta-analysis including 28,141 individuals identified
      nine single nucleotide polymorphisms (SNPs) associated with altered SUA level in
      a Caucasian population. However, raised SUA level alone is not sufficient for the
      development of gout arthritis and most of these SNPs have not been studied in a
      Han Chinese population. Here, we performed a case-control association analysis to
      investigate the relationship between these SUA correlated SNPs and gout arthritis
      in Han Chinese. METHODS: A total of 622 ascertained gout p9atients and 917
      healthy controls were genotyped. Genome-wide significant SNPs, rs12129861,
      rs780094, rs734553, rs742132, rs1183201, rs12356193, rs17300741 and rs505802 in
      the previous SUA study, were selected for our analysis. RESULTS: No deviation
      from the Hardy-Weinberg equilibrium was observed either in the case or control
      cohorts (corrected p > 0.05). Three SNPs, rs780094 (located in GCKR, corrected p
      = 1.78E(-4), OR = 0.723), rs1183201 (located in SLC17A1, corrected p = 1.39E(-7),
      OR = 0.572) and rs505802 (located in SLC22A12, corrected p = 0.007, OR = 0.747),
      were significantly associated with gout on allelic level independent of potential
      cofounding traits. While the remaining SNPs were not replicated. We also found
      significant associations of uric acid concentrations with these three SNPs
      (rs780094 in GCKR, corrected p = 3.94E(-5); rs1183201 in SLC17A1, corrected p =
      0.005; rs505802 in SLC22A12, corrected p = 0.003) and of triglycerides with
      rs780094 (located in GCKR, corrected p = 2.96E(-4)). Unfortunately, SNP-SNP
      interactions for these three significant SNPs were not detected (rs780094 vs
      rs1183201, p = 0.402; rs780094 vs rs505802, p = 0.434; rs1183201 vs rs505802, p =
      0.143). CONCLUSIONS: Three SUA correlated SNPs in Caucasian population, rs780094
      in GCKR, rs1183201 in SLC17A1 and rs505802 in SLC22A12 were confirmed to be
      associated with gout arthritis and uric acid concentrations in Han Chinese males.
      Considering genetic differences among populations and complicated pathogenesis of
      gout arthritis, more validating tests in independent populations and relevant
      functional experiments are suggested in future.

PMID- 26290328
TI  - Abatacept decreases disease activity in a absence of CD4(+) T cells in a collagen
      induced arthritis model.
AB  - INTRODUCTION: Abatacept is a fusion protein of human cytotoxic T-lymphocyte
      associated protein (CTLA)-4 and the Fc portion of human immunoglobulin G1 (IgG1).
      It is believed to be effective in the treatment of rheumatoid arthritis by
      inhibiting costimulation of T cells via blocking CD28-B7 interactions as CTLA-4
      binds to both B7.1 (CD80) and B7.2 (CD86). However, the interaction of CD28 with
      B7 molecules is crucial for activation of naive cells, whereas it is unclear
      whether the action of already activated CD4(+) T cells, which are readily present
      in established disease, also depends on this interaction. The aim of this study
      was to determine whether the mode of action of abatacept depends solely on its
      ability to halt T cell activation in established disease. METHODS: Arthritis was
      induced in thymectomized male DBA/1 mice by immunisation with bovine collagen
      type II. The mice were subsequently depleted for CD4(+) T cells. Abatacept or
      control treatment was started when 80 % of the mice showed signs of arthritis.
      Arthritis severity was monitored by clinical scoring of the paws, and anti
      collagen antibody levels over time were determined by enzyme-linked immunosorbent
      assay. RESULTS: Treatment with abatacept in the absence of CD4(+) T cells
      resulted in lower disease activity. This was associated with decreasing levels of
      collagen-specific IgG1 and IgG2a antibodies, whereas the antibody levels in
      control or CD4(+) T cell-depleted mice increased over time. CONCLUSIONS: These
      results show that abatacept decreased disease activity in the absence of CD4(+) T
      cells, indicating that the mode of action of abatacept in established arthritis
      does not depend entirely on its effects on CD4(+) T cell activation.

PMID- 26290329
TI  - Predictors of primary health care pharmaceutical expenditure by districts in
      Uganda and implications for budget setting and allocation.
AB  - BACKGROUND: There is need for the Uganda Ministry of Health to understand
      predictors of primary health care pharmaceutical expenditure among districts in
      order to guide budget setting and to improve efficiency in allocation of the set
      budget among districts. METHODS: Cross sectional, retrospective observational
      study using secondary data. The value of pharmaceuticals procured by primary
      health care facilities in 87 randomly selected districts for the Financial Year
      2011/2012 was collected. Various specifications of the dependent variable
      (pharmaceutical expenditure) were used: total pharmaceutical expenditure, Per
      capita district pharmaceutical expenditure, pharmaceutical expenditure per
      district health facility and pharmaceutical expenditure per outpatient department
      visit. Andersen's behaviour model of health services utilisation was used as
      conceptual framework to identify independent variables likely to influence health
      care utilisation and hence pharmaceutical expenditure. Econometric analysis was
      conducted to estimate parameters of various regression models. RESULTS: All
      models were significant overall (P < 0.01), with explanatory power ranging from
      51 to 82%. The log linear model for total pharmaceutical expenditure explained
      about 80% of the observed variation in total pharmaceutical expenditure (Adjusted
      R(2) = 0.797) and contained the following variables: Immunisation coverage, Total
      outpatient department attendance, Urbanisation, Total number of government health
      facilities and total number of Health Centre IIs. The model based on Per capita
      Pharmaceutical expenditure explained about 50% of the observed variation in per
      capita pharmaceutical expenditure (Adjusted R(2) = 0.513) and was more balanced
      with the following variables: Outpatient per capita attendance, percentage of
      rural population below poverty line 2005, Male Literacy rate, Whether a district
      is characterised by MOH as difficult to reach or not and the Human poverty index.
      CONCLUSIONS: The log-linear model based on total pharmaceutical expenditure works
      acceptably well and can be considered useful for predicting future total
      pharmaceutical expenditure following observed trends. It can be used as a simple
      tool for rough estimation of the potential overall national primary health
      pharmaceutical expenditure to guide budget setting. The model based on
      pharmaceutical expenditure per capita is a more balanced model containing both
      need and enabling factor variables. These variables would be useful in allocating
      any set budget to districts.

PMID- 26290330
TI  - A psychometric assessment of the St. George's respiratory questionnaire in
      patients with COPD using Rasch model analysis.
AB  - BACKGROUND: The St. George's Respiratory Questionnaire (SGRQ) was a widely used
      tool to assess disease impact on patients with obstructive airways disease.
      Although traditional methods have generally supported construct validity and
      internal consistency reliability of SGRQ, such methods cannot facilitate the
      evaluation of whether items are equivalent to different individuals. The purpose
      of this study is to rigorously examine the psychometric properties of the SGRQ in
      patients with chronic obstructive pulmonary disease (COPD) using Rasch model
      analysis. METHODS: A methodological research was conducted on SGRQ in a sample of
      240 male patients with COPD recruited from the outpatient services in Central
      Taiwan. The psychometric properties of the SGRQ were examined using Rasch model
      analysis with a mixed rating scale and partial credit mode by Winsteps software.
      The level of matching between the item's difficulty and person's ability was
      analyzed by item-person targeting as well as ceiling and floor effects. Item
      person maps were also examined for checking the location of the item's difficulty
      and person's measures along the same scale. Finally, the differential item
      functioning (DIF) was examined to measure group equivalence associated with age
      and disease's severity. RESULTS: Each of the three domains (Symptom, Activity,
      Impact) of the SGRQ was found to be unidimensionality. The person separation
      index ranged from 1.21 (Symptom domain) to 2.50 (Activity domain). There was a
      good targeting for the SGRQ domains, except the Impact domain (1.36). The
      percentage of ceiling and floor effects were below 10%, except the ceiling effect
      in the Impact domain (26.25%). From item-person maps, gaps of location of item
      corresponded to patient's ability were identified. The results have also showed
      that many items in SGRQ revealed age or severity related DIF. CONCLUSIONS: Except
      the Symptom domain of SGRQ, the others have a reliabile internal consistency and
      a good hierarchical structure. The results of Rasch model analysis can highlight
      aspects for scale improvement, such as gap, duplicate items or scale responses.
      There was some age or severity related DIF indicating somewhat unstable across
      different characteristics of group. IRB No.: DMR94-IRB-179.

PMID- 26290331
TI  - Advancing the strategic use of HIV operations research to strengthen local
      policies and programmes: the Research to Prevention Project.
AB  - In the field of HIV prevention, there is renewed interest in operations research
      (OR) within an implementation science framework. The ultimate goal of such
      studies is to generate new knowledge that can inform local programmes and
      policies, thus improving access, quality, efficiency and effectiveness. Using
      four case studies from the USAID-funded Research to Prevention (R2P) project, we
      highlight the strategic use of OR and the impact it can have on shaping the focus
      and content of HIV prevention programming across geographic and epidemic settings
      and populations. These case studies, which include experiences from several sub
      Saharan African countries and the Caribbean, emphasize four unique ways that R2P
      projects utilized OR to stimulate change in a given context, including: (1)
      translating findings from clinical trials to real-world settings; (2) adapting
      promising structural interventions to a new context; (3) tailoring effective
      interventions to underserved populations; and (4) prioritizing key populations
      within a national response to HIV. Carefully crafted OR can bridge the common gap
      that exists between research-generated knowledge and field-based practice, lead
      to substantial, real-world changes in national policies and programmes, and
      strengthen local organizations and the use of data to be more responsive to a
      given topic or population, ultimately supporting a locally tailored HIV response.

PMID- 26290332
TI  - Characterization of a second open reading frame in genome segment 10 of
      bluetongue virus.
AB  - Viruses have often evolved overlapping reading frames in order to maximize their
      coding capacity. Until recently, the segmented dsRNA genome of viruses of the
      Orbivirus genus was thought to be monocistronic, but the identification of the
      bluetongue virus (BTV) NS4 protein changed this assumption. A small ORF in
      segment 10, overlapping the NS3 ORF in the +1 position, is maintained in more
      than 300 strains of the 27 different BTV serotypes and in more than 200 strains
      of the phylogenetically related African horse sickness virus (AHSV). In BTV, this
      ORF (named S10-ORF2 in this study) encodes a putative protein 50-59 residues in
      length and appears to be under strong positive selection. HA- or GFP-tagged
      versions of S10-ORF2 expressed from transfected plasmids localized within the
      nucleoli of transfected cells, unless a putative nucleolar localization signal
      was mutated. S10-ORF2 inhibited gene expression, but not RNA translation, in
      transient transfection reporter assays. In both mammalian and insect cells, BTV
      S10-ORF2 deletion mutants (BTV8DeltaS10-ORF2) displayed similar replication
      kinetics to wt virus. In vivo, S10-ORF2 deletion mutants were pathogenic in mouse
      models of disease. Although further evidence is required for S10-ORF2 expression
      during infection, the data presented provide an initial characterization of this
      ORF. 

PMID- 26290334
TI  - Self-assembling process of Oxalamide compounds and their nucleation efficiency in
      bio-degradable Poly(hydroxyalkanoate)s.
AB  - One of the key requirements in semi-crystalline polyesters, synthetic or bio
      based, is the control on crystallization rate and crystallinity. One of the
      limiting factors in the commercialization of the bio-based polyesters, for
      example polyhydroxyalkanoates synthesized by bacteria for energy storage
      purposes, is the slow crystallization rate. In this study, we show that by
      tailoring the molecular structure of oxalamide compounds, it is possible to
      dissolve these compounds in molten poly(hydroxybutyrate) (PHB), having a
      hydroxyvalerate co-monomer content of less than 2 mol%. Upon cooling the polymer
      melt, the homogeneously dispersed oxalamide compound crystallizes just below the
      melting temperature of the polymer. The phase-separated compound reduces the
      nucleation barrier of the polymer, thus enhancing the crystallization rate,
      nucleation density and crystallinity. The findings reported in this study provide
      a generic route for the molecular design of oxalamide-based compounds that can be
      used for enhancing nucleation efficiency of semi-crystalline bio-based
      polyesters. 

PMID- 26290333
TI  - DNA methylation and gene expression dynamics during spermatogonial stem cell
      differentiation in the early postnatal mouse testis.
AB  - BACKGROUND: In the male germline, neonatal prospermatogonia give rise to
      spermatogonia, which include stem cell population (undifferentiated
      spermatogonia) that supports continuous spermatogenesis in adults. Although the
      levels of DNA methyltransferases change dynamically in the neonatal and early
      postnatal male germ cells, detailed genome-wide DNA methylation profiles of these
      cells during the stem cell formation and differentiation have not been reported.
      RESULTS: To understand the regulation of spermatogonial stem cell formation and
      differentiation, we examined the DNA methylation and gene expression dynamics of
      male mouse germ cells at the critical stages: neonatal prospermatogonia, and
      early postntal (day 7) undifferentiated and differentiating spermatogonia. We
      found large partially methylated domains similar to those found in cancer cells
      and placenta in all these germ cells, and high levels of non-CG methylation and 5
      hydroxymethylcytosines in neonatal prospermatogonia. Although the global CG
      methylation levels were stable in early postnatal male germ cells, and despite
      the reported scarcity of differential methylation in the adult spermatogonial
      stem cells, we identified many regions showing stage-specific differential
      methylation in and around genes important for stem cell function and
      spermatogenesis. These regions contained binding sites for specific transcription
      factors including the SOX family members. CONCLUSIONS: Our findings show a
      distinctive and dynamic regulation of DNA methylation during spermatogonial stem
      cell formation and differentiation in the neonatal and early postnatal testes.
      Furthermore, we revealed a unique accumulation and distribution of non-CG
      methylation and 5hmC marks in neonatal prospermatogonia. These findings contrast
      with the reported scarcity of differential methylation in adult spermatogonial
      stem cell differentiation and represent a unique phase of male germ cell
      development.

PMID- 26290335
TI  - De novo transcriptome assembly and analysis of Sf21 cells using illumina paired
      end sequencing.
AB  - Spodoptera is an important polyphagous agricultural insect pest in the tropical
      world. The genomic details are limited to understand the pest biology at
      molecular level. In the present study, we sequenced and assembled the
      transcriptome from Sf21 cells into a non redundant set of 24,038 contigs of ~
      47.38 Mb in size. A total of 26,390 unigenes were identified from the assembled
      transcripts and their annotation revealed the prevalent protein domains in Sf21
      cells. The present study would provide a resource for gene discovery and
      development of functional molecular markers to understand the biology of S.
      frugiperda.

PMID- 26290336
TI  - Retraction: 'An endogenous, systemic RNAi pathway in plants'.

PMID- 26290338
TI  - Nuclear import of CaMV P6 is required for infection and suppression of the RNA
      silencing factor DRB4.

PMID- 26290337
TI  - Polynucleotide kinase-phosphatase enables neurogenesis via multiple DNA repair
      pathways to maintain genome stability.
AB  - Polynucleotide kinase-phosphatase (PNKP) is a DNA repair factor possessing both
      5'-kinase and 3'-phosphatase activities to modify ends of a DNA break prior to
      ligation. Recently, decreased PNKP levels were identified as the cause of severe
      neuropathology present in the human microcephaly with seizures (MCSZ) syndrome.
      Utilizing novel murine Pnkp alleles that attenuate expression and a T424GfsX48
      frame-shift allele identified in MCSZ individuals, we determined how PNKP
      inactivation impacts neurogenesis. Mice with PNKP inactivation in neural
      progenitors manifest neurodevelopmental abnormalities and postnatal death. This
      severe phenotype involved defective base excision repair and non-homologous end
      joining, pathways required for repair of both DNA single- and double-strand
      breaks. Although mice homozygous for the T424GfsX48 allele were lethal
      embryonically, attenuated PNKP levels (akin to MCSZ) showed general
      neurodevelopmental defects, including microcephaly, indicating a critical
      developmental PNKP threshold. Directed postnatal neural inactivation of PNKP
      affected specific subpopulations including oligodendrocytes, indicating a broad
      requirement for genome maintenance, both during and after neurogenesis. These
      data illuminate the basis for selective neural vulnerability in DNA repair
      deficiency disease. 

PMID- 26290339
TI  - Letter to the Editor: Negative Pressure Wound Therapy in Grade IIIB Tibial
      Fractures: Fewer Infections and Fewer Flap Procedures?

PMID- 26290340
TI  - CORR Insights((r)): No Difference in Reoperations at 2 Years Between Ceramic-on
      metal and Metal-on-metal THA: A Randomized Trial.

PMID- 26290341
TI  - Have Changes in Treatment of Late-detected Developmental Dysplasia of the Hip
      During the Last Decades Led to Better Radiographic Outcome?
AB  - BACKGROUND: Despite considerable changes in the treatment of of late-detected
      congenital or developmental hip dislocation (DDH) during the last 50 years, it is
      unclear whether and to what degree these changes have led to better long-term
      outcome for the patients. QUESTIONS/PURPOSES: The aims of this study were to see
      whether decreasing use of skin traction and instead a more aggressive approach to
      open reduction resulted in (1) reduced use of secondary procedures; (2) improved
      radiographic appearance of the hips at long-term followup; and (3) changes in the
      proportion of patients developing avascular necrosis. METHODS: Two groups of
      patients were compared retrospectively. Inclusion criteria were patient age older
      than 3 months and younger than 5 years at the initiation of treatment, no
      associated anomaly, no previous treatment in other hospitals, and available
      radiographs from the time of diagnosis to skeletal maturity. Group A consisted of
      56 patients (51 girls [91%]; 74 hips) primarily treated during the period 1958 to
      1962. Group B comprised 38 patients (36 girls [95%]; 40 hips) treated during the
      period 1996 to 2002. The mean age at the time of hip reduction was 20 months (SD
      9.6) in Group A and 17 months (SD 11.9) in Group B. The mean time in skin
      traction had decreased from 35 days (SD 12.5) to 11 days (SD 5.7) over the years
      (p < 0.001). Open reduction was performed in six of 74 hips (8%) in Group A and
      15 of 40 hips (37%) in Group B (p < 0.001). The immobilization time in the hip
      spica had decreased from 9 to 6 months (p < 0.001). The indication for secondary
      procedures to correct residual dysplasia was center-edge angle < 20 degrees  and
      was similar in both groups. A modified version of the radiographic classification
      of Severin was used to compare the results. RESULTS: Secondary procedures to
      correct residual dysplasia were performed in 28 of 74 hips (38%) in Group A and
      seven of 40 hips (18%) in Group B (odds ratio [OR], 0.35; 95% confidence interval
      [CI], 0.14-0.89; p = 0.025) At skeletal maturity, the proportion of patients with
      satisfactory radiographic results (Severin Grades I/II) was larger in Group B (33
      of 40 hips [82%]) than in Group A (46 of 74 hips [62%]; OR, 0.35; CI, 0.14-0.89;
      p = 0.025). Femoral head coverage, assessed as the center-edge angle, was greater
      in Group B than in Group A (mean 26 degrees  versus 22 degrees ; CI, 0.8-7.9; p =
      0.016). There was no difference in the proportion of avascular necrosis of the
      femoral head (seven of 74 hips [9%] in Group A and five of 40 [13%] in Group B;
      OR, 1.4; CI, 0.4-4.6; p = 0.614). CONCLUSIONS: The move away from prolonged use
      of skin traction and toward more frequent open reduction for children with a late
      diagnosis of DDH appears to result in fewer secondary procedures and a better
      radiographic appearance of the hip at skeletal maturity. Based on the present
      results, we cannot conclude whether preliminary traction is needed; this question
      should be evaluated in future long-term studies with a prospective, randomized
      design. LEVEL OF EVIDENCE: Level III, therapeutic study.

PMID- 26290342
TI  - What are the Risk Factors for Cerebrovascular Accidents After Elective
      Orthopaedic Surgery?
AB  - BACKGROUND: Perioperative cerebrovascular accidents (CVAs) are one of the leading
      causes of patient morbidity, mortality, and medical costs. However, little is
      known regarding the rates of these events and risk factors for CVA after elective
      orthopaedic surgery. QUESTIONS/PURPOSES: Our goals were to (1) establish the
      national, baseline proportion of patients experiencing a 30-day CVA and the
      timing of CVA; and (2) determine independent risk factors for 30-day CVA rates
      after common elective orthopaedic procedures. METHODS: Patients undergoing
      elective TKA, THA, posterior or posterolateral lumbar fusion, anterior cervical
      discectomy and fusion, and total shoulder arthroplasty, from 2006 to 2012, were
      identified from the American College of Surgeons National Surgical Quality
      Improvement Program((r)) database. A total of 42,150 patients met inclusion
      criteria. Thirty-day CVA rates were recorded for each procedure, and patients
      were assessed for characteristics associated with CVA through univariate
      analysis. Multivariate regression models were created to identify independent
      risk factors for CVA. RESULTS: A total of 55 (0.13%) patients experienced a CVA
      within 30 days of the procedure, occurring a median of 2 days after surgery
      (range, 1-30 days) with 0.08% of patients experiencing a CVA after TKA, 0.15%
      after THA, 0.00% after single-level anterior cervical discectomy and fusion,
      0.38% after multilevel anterior cervical discectomy and fusions, 0.20% after
      single-level posterior or posterolateral lumbar fusion, 0.70% after multilevel
      posterior or posterolateral lumbar fusion, and 0.22% after total shoulder
      arthroplasty. Independent risk factors for CVA included age of 75 years or older
      (odds ratio [OR], 2.50; 95% CI, 1.44-4.35; p = 0.001), insulin-dependent diabetes
      mellitus (OR, 3.08; CI, 1.47-6.45; p = 0.003), hypertension (OR, 2.71; CI, 1.19
      6.13; p = 0.017), history of transient ischemic attack (OR, 2.83; CI, 1.24-6.45;
      p = 0.013), dyspnea (OR, 2.51; CI, 1.30-4.86; p = 0.006), chronic obstructive
      pulmonary disease (OR, 2.33; CI, 1.06-5.13; p = 0.036), and operative time of 180
      minutes or greater (OR, 3.25; CI 1.60-6.60; p = 0.001). CONCLUSIONS: Numerous
      nonmodifiable patient comorbidities and increased operative time were associated
      with CVA after elective orthopaedic procedures. However, the American College of
      Surgeons National Surgical Quality Improvement Program((r)) database does not
      code for cardiac arrhythmia or atrial fibrillation, which other studies have
      suggested may be important predictor variables; those may be important risk
      factors, although we were unable to evaluate them in our study. Surgeons should
      counsel patients with these risk factors and limit their operative time to reduce
      the risk of these adverse events, and future studies should examine other patient
      characteristics such as arrhythmia and noncoronary heart disease and assess the
      role of pharmacologic prophylaxis in patients with these risk factors. LEVEL OF
      EVIDENCE: Level III, prognostic study.

PMID- 26290343
TI  - Oxidized zirconium head on crosslinked polyethylene liner in total hip
      arthroplasty: a 7- to 12-year in vivo comparative wear study.
AB  - BACKGROUND: Osteolysis resulting from wear debris production from the bearing
      surfaces is a major factor limiting long-term survival of hip implants. Oxidized
      zirconium head on crosslinked polyethylene (XLPE) is a modern bearing coupling.
      However, midterm in vivo wear data of this coupling are not known.
      QUESTIONS/PURPOSES: The purpose of this study was to investigate in vivo whether
      the combination of an oxidized zirconium femoral head on XLPE produces less wear
      than a ceramic head on XLPE or a ceramic head on conventional polyethylene (CPE)
      couplings and whether any of these bearing combinations results in higher hip
      scores. METHODS: Between 2003 and 2007, we performed 356 total hip arthroplasties
      in 288 patients; of those, 199 (69.1%) patients (199 hips) were enrolled in what
      began as a randomized trial. Unfortunately, after the 57(th) patient, the
      randomization process was halted because of patients' preference for the oxidized
      zirconium bearing instead of the ceramic after (as they were informed by the
      consent form), and after that, alternate allocation to the study groups was
      performed. Hips were allocated into four groups: in Group A, a 28-mm ceramic head
      on CPE was used; in Group B, a 28-mm ceramic head on XLPE; in Group C, a 28-mm
      Oxinium head on XLPE; and in Group D, a 32-mm Oxinium head on XLPE. The authors
      prospectively collected in vivo wear data (linear wear, linear wear rate,
      volumetric wear, and volumetric wear rate) using PolyWare software. Preoperative
      and postoperative clinical data, including Harris and Oxford hip scores, were
      also collected at regular intervals. Of those patients enrolled, 188 (95%) were
      available for final followup at a minimum of 7 years (mean, 9 years; range, 7-12
      years). RESULTS: All bearing surfaces showed a varying high bedding-in effect
      (plastic deformation of the liner) up to the second postoperative year. At 5
      years both oxidized zirconium on XLPE groups showed lower (p < 0.01) volumetric
      wear (mean +/- SD mm(3)) and volumetric wear rates (mean +/- SD mm(3)/year)
      (Group C: 310 +/- 55-206 +/- 55 mm(3)/year, Group D: 320 +/- 58-205 +/- 61
      mm(3)/year) when compared with ceramic on CPE (Group A: 791 +/- 124-306 +/- 85
      mm(3)/year) and ceramic on XLPE (Group B: 1420 +/- 223-366 +/- 88 mm(3)/year)
      groups. For those patients who had completed 10 years of followup (20 patients
      [44.5%] of Group A, 21 [45.7%] of Group B, 23 [47.9%] of Group C, and 22 [44.9%]
      of Group D), at 10 years, both oxidized zirconium on XLPE groups also showed
      lower (p < 0.01) volumetric wear (mean +/- SD mm(3)) and volumetric wear rates
      (mean +/- SD mm(3)/year) (Group C: 356 +/- 64 to 215 +/- 54 mm(3)/year, Group D:
      354 +/- 50 to 210 +/- 64 mm(3)/year) when compared with ceramic on CPE (Group A:
      895 +/- 131 to 380 +/- 80 mm(3)/year) and ceramic on XLPE (Group B: 1625 +/- 253
      to 480 +/- 101 mm(3)/year) groups. When wear rates of both oxidized zirconium
      groups were compared, no differences were found at any time interval with the
      numbers available. Two hips (one from Group A and one from Group B) are scheduled
      for revision as a result of wear and osteolysis. There were no differences in hip
      scores among the groups with the numbers available. CONCLUSIONS: In this study,
      in vivo wear parameters were lower when the combination of an oxidized zirconium
      head on XLPE liner was used at an average of 9 years (range, 7-12 years)
      followup. Further larger-scale clinical studies should confirm these findings and
      evaluate osteolysis and revision rates in association with the use of this
      bearing coupling. LEVEL OF EVIDENCE: Level II, therapeutic study.

PMID- 26290344
TI  - What Is the Impact of Comorbidities on Self-rated Hand Function in Patients With
      Symptomatic Trapeziometacarpal Arthritis?
AB  - BACKGROUND: The thumb trapeziometacarpal joint is one of the most common sites of
      arthritic degeneration prompting specialty care. Surgical treatment algorithms
      are based on radiographic arthritic progression. However, the pain and disability
      attributable to trapeziometacarpal arthritis do not correlate with arthritic
      stage, and depression has independently predicted poorer self-rated hand function
      both at baseline and after treatment in patients' atraumatic hand conditions.
      QUESTIONS/PURPOSES: (1) Does thumb trapeziometacarpal osteoarthritis impact both
      self-perceived general health and hand function? (2) Do depression and other
      comorbid conditions differentially impact patient-rated hand function based on
      the presence or absence of symptomatic trapeziometacarpal arthritis? (3) How do
      disease-specific, patient demographics and comorbid conditions impact self
      reported hand function in patients with trapeziometacarpal osteoarthritis?
      METHODS: This cross-sectional study compared patients with symptomatic
      trapeziometacarpal osteoarthritis (n = 47) with matched control subjects without
      a symptomatic hand condition (n = 47). All participants self-reported medical
      (including depression) and musculoskeletal comorbidities and completed the SF-36
      and the Michigan Hand Questionnaire (MHQ). Bivariate statistical analyses
      contrasted the patients with trapeziometacarpal osteoarthritis to control
      subjects. Linear regression modeling determined the impact of subject demographic
      data, comorbidity burden, and examination findings on total MHQ scores in
      patients with trapeziometacarpal arthritis. RESULTS: Patients with scored
      trapeziometacarpal osteoarthritis indicated poorer perceived general health on
      the SF-36 categories of limitations resulting from physical health (52 +/- 29
      versus 71 +/- 31, mean difference 19 [95% confidence interval {CI}, 7-31], p =
      0.003) and limitations resulting from emotional problems (50 +/- 27 versus 67 +/-
      50, mean difference 17 [95% CI, 3-33], p = 0.022) compared with control subjects.
      Self-reported depression was associated with worse hand function (total MHQ
      score) in patients with trapeziometacarpal arthritis (69 +/- 20 versus 49 +/- 22:
      mean difference -20 [95% CI, -5 to-36], p = 0.012) but not in control patients
      (90 +/- 13 versus 84 +/- 20: mean difference -5 [95% CI, -8 to 19], p = 0.404).
      In multivariate modeling, depression (beta -20, [95% CI, -5 to -34], p = 0.009)
      and upper extremity comorbidities (beta -25, [95% CI, -10 to -40], p = 0.002)
      were both associated with reduced total MHQ scores in patients with
      trapeziometacarpal osteoarthritis, and those factors accounted for 34% of the
      variance in the MHQ score. CONCLUSIONS: When interpreting patient-rated hand
      disability in patients presenting with symptomatic trapeziometacarpal
      osteoarthritis, scores should be interpreted after accounting for the presence of
      depression and upper extremity comorbidities. LEVEL OF EVIDENCE: Level III,
      prognostic study.

PMID- 26290345
TI  - Arthroscopy for Knee Osteoarthritis Has Not Decreased After a Clinical Trial.
AB  - BACKGROUND: Multiple clinical trials have shown that arthroscopy for knee
      osteoarthritis is not efficacious. It is unclear how these studies have affected
      orthopaedic practice in the USA. QUESTIONS/PURPOSES: We questioned whether, in
      the Veterans Health Administration system, rates of knee arthroscopy in patients
      with osteoarthritis have changed after publication of the initial clinical trial
      by Moseley et al. in 2002, and whether rates of arthroplasty within 2 years of
      arthroscopy have changed during the same period. METHODS: Patients 50 years and
      older with knee osteoarthritis who underwent arthroscopy between 1998 and 2010
      were retrospectively identified and an annual arthroscopy rate was calculated
      from 1998 through 2002 and from 2006 through 2010. Patients who underwent knee
      arthroplasty within 2 years of arthroscopy during each period were identified,
      and a 2-year conversion to arthroplasty rate was calculated. RESULTS: Between
      1998 and 2002, the annual arthroscopy rate decreased from 4% to 3%. Of these
      arthroscopies, 4% were converted to arthroplasty within 2 years. Between 2006 and
      2010, the annual arthroscopy rate increased from 3% to 4%. Of these
      arthroscopies, 5% were converted to arthroplasty within 2 years. CONCLUSIONS:
      Rates of arthroscopy in patients with knee osteoarthritis and conversion to
      arthroplasty within 2 years have not decreased with time. It may be that evidence
      alone is not sufficient to alter practice patterns or that arthroscopy rates for
      arthritis for patients in the Veterans Health Administration system were already
      so low that the results of the initial clinical trial had no substantial effect.
      LEVEL OF EVIDENCE: Level III, Retrospective cohort study.

PMID- 26290346
TI  - Determinants of Hip Displacement in Children With Cerebral Palsy.
AB  - BACKGROUND: Coxa valga and femoral anteversion often are seen in patients with
      spastic hip displacement and osteotomy is recommended. However, the relationship
      between femoral deformities and hip displacement has not been clearly defined and
      other factors, such as joint motion and posture, should be considered before
      recommending treatment. QUESTIONS: For children with cerebral palsy with Gross
      Motor Function Classification System Level IV or V, we questioned (1) whether hip
      abduction range correlates with hip displacement, (2) what the relationships are
      between proximal femoral deformities and hip displacement, and (3) whether the
      patient with a windblown posture has greater degrees of femoral anteversion?
      METHODS: We retrospectively studied 31 consecutive children with cerebral palsy
      with Level IV or V gross motor function who underwent three-dimensional CT for
      preoperative assessment of hip displacement between January 2010 and December
      2013. Among the children, 23 had a windblown posture and eight had symmetric hip
      motion. Femoral anteversion and true neck-shaft angle were measured from the
      three-dimensional CT images. Migration percentage was the dependent variable we
      chose to study in relation to femoral anteversion, neck-shaft angle, maximal hip
      abduction, and hip flexion contracture, using correlations and multiple linear
      regressions. Using ANOVA and Scheffe's post hoc tests, we analyzed and compared
      the data of 23 abducted hips and 23 adducted hips in the 23 children with
      windblown posture and in 16 displaced hips in the eight children with symmetric
      hip abduction. RESULTS: Greater migration percentage was associated with less hip
      abduction range (r = -0.86; p < 0.001). Femoral anteversion had a weak
      correlation (r = 0.28; p < 0.05) to migration percentage, and the association
      became insignificant after considering hip abduction motion. Adducted windblown
      hips had greater femoral anteversion than the symmetric displaced hips and
      abducted windblown hips (46 degrees  vs 36 degrees  and 38 degrees ,
      respectively; p < 0.05). CONCLUSIONS: Our study results did not support a
      relationship between femoral deformities and hip displacement after considering
      gross motor function and hip abduction motion. Greater femoral anteversion was
      noted in the adducted hips of patients with windblown posture, and derotation
      osteotomy is especially recommended. LEVEL OF EVIDENCE: Level III, diagnostic
      study.

PMID- 26290347
TI  - Detecting recent selective sweeps while controlling for mutation rate and
      background selection.
AB  - A composite likelihood ratio test implemented in the program sweepfinder is a
      commonly used method for scanning a genome for recent selective sweeps.
      sweepfinder uses information on the spatial pattern (along the chromosome) of the
      site frequency spectrum around the selected locus. To avoid confounding effects
      of background selection and variation in the mutation process along the genome,
      the method is typically applied only to sites that are variable within species.
      However, the power to detect and localize selective sweeps can be greatly
      improved if invariable sites are also included in the analysis. In the spirit of
      a Hudson-Kreitman-Aguade test, we suggest adding fixed differences relative to an
      out-group to account for variation in mutation rate, thereby facilitating more
      robust and powerful analyses. We also develop a method for including background
      selection, modelled as a local reduction in the effective population size. Using
      simulations, we show that these advances lead to a gain in power while
      maintaining robustness to mutation rate variation. Furthermore, the new method
      also provides more precise localization of the causative mutation than methods
      using the spatial pattern of segregating sites alone.

PMID- 26290349
TI  - T-cell Activation Induces Dynamic Changes in miRNA Expression Patterns in CD4 and
      CD8 T-cell Subsets.
AB  - T-cell activation affects microRNA (miRNA) expression in T-cell subsets. However,
      little is known about the kinetics of miRNA regulation and possible differences
      between CD4 and CD8 T cells. In this study we set out to analyze the kinetics of
      activation-induced expression regulation of twelve pre-selected miRNAs. The
      dynamics of the expression of these miRNAs was studied in sorted CD4 and CD8
      CD45RO- T cells of healthy individuals stimulated with alphaCD3/alphaCD28
      antibodies. Analysis of miRNA levels at day 3, 5, 7 and 10 showed significant
      activation-induced changes in expression levels of all twelve miRNAs. Expression
      levels of nine miRNAs, including miR-21, miR-146a and miR-155, were induced
      following activation, whereas expression of three miRNAs, including miR-31, were
      decreased following activation. The expression changes of miR-18a and miR-155 was
      relatively early, at day 3, whereas expression of miR-451, miR-21 and miR-146a
      was evident at day 5, 7 and 10, respectively. Four miRNAs showed a differential
      regulation between CD4 and CD8 T cells. Induction of miR-18a and miR-21 was more
      pronounced and occurred earlier in CD4 T cells compared to CD8 T cells.
      Downregulation of miR-223 and miR-451 was also more pronounced in CD4 T cells
      compared to CD8 T cells. In conclusion, we show a complex pattern of miRNA
      expression regulation upon T-cell activation with early and late as well as CD4
      and CD8 T-cell specific changes. These differences might be the result of
      differences in kinetics and efficiency of CD4 and CD8 T cells in response to
      antigen priming.

PMID- 26290350
TI  - Gene-Environment Interaction Effects of Peer Deviance, Parental Knowledge and
      Stressful Life Events on Adolescent Alcohol Use.
AB  - The purpose of this study was to address two methodological issues that have
      called into question whether previously reported gene-environment interaction
      (GxE) effects for adolescent alcohol use are 'real'. These issues are (1) the
      potential correlation between the environmental moderator and the outcome across
      twins and (2) non-linear transformations of the behavioral outcome. Three
      environments that have been previously studied (peer deviance, parental
      knowledge, and potentially stressful life events) were examined here. For each
      moderator (peer deviance, parental knowledge, and potentially stressful life
      events), a series of models was fit to both a raw and transformed measure of
      monthly adolescent alcohol use in a sample that included 825 dizygotic (DZ) and
      803 monozygotic (MZ) twin pairs. The results showed that the moderating effect of
      peer deviance was robust to transformation, and that although the significance of
      moderating effects of parental knowledge and potentially stressful life events
      were dependent on the scale of the adolescent alcohol use outcome, the overall
      results were consistent across transformation. In addition, the findings did not
      vary across statistical models. The consistency of the peer deviance results and
      the shift of the parental knowledge and potentially stressful life events results
      between trending and significant, shed some light on why previous findings for
      certain moderators have been inconsistent and emphasize the importance of
      considering both methodological issues and previous findings when conducting and
      interpreting GxE analyses. 

PMID- 26290351
TI  - Molecular Epidemiological Investigation of Thalassemia in the Chengdu Region,
      Sichuan Province, Southwest China.
AB  - Thalassemia is the most common inherited disease in southern China. However, this
      disorder is usually ignored by the health system in the Sichuan Province due to
      the lack of epidemiological data. To provide basic epidemiological data for
      thalassemia screening, genetic counseling, and prenatal diagnosis (PND) in the
      Chengdu region, a total of 3262 healthy subjects were assessed by complete blood
      count (CBC), reverse dot-blot gene chip, gap-polymerase chain reaction (gap-PCR),
      and PCR-DNA sequencing. A frequency of heterozygous thalassemia of 3.43%
      (112/3262) was found, of which 2.21% (72/3262) patients carried alpha-thalassemia
      (alpha-thal), 1.19% (39/3262) beta-thalassemia (beta-thal) and 0.3% (1/3262)
      hereditary persistence of fetal hemoglobin (Hb) (HPFH)/deltabeta-thalassemia
      (deltabeta-thal). Four types of alpha-thal mutations were found, the most
      prevalent being - -(SEA) (68.06%), followed by -alpha(3.7) (rightward deletion,
      25.0%), Hb Quong Sze (Hb QS; HBA2: c.377 T > C) (4.17%), and -alpha(4.2)
      (leftward deletion, 2.78%). The seven beta-thal mutations included: codons 41/42
      (-TTCT), HBB: c.126_129delCTTT (13/39, 33.33%); codon 17 (A > T), HBB: c.52 A > T
      (11/39, 28.95%); IVS-II-654 (C > T), HBB: c.316-197 C > T (9/39, 23.68%); -28 (A
      > G), HBB: c.-78 A > G (3/39, 7.69%); -29 (A > G), HBB: c.-79 A > G (1/39,
      2.56%); codons 27/28 (+C), HBB: c.84_85insC (1/39, 2.56%), and the rare IVS-II
      850 (G > T), HBB: c.316-1 G > T (1/39, 2.56%). Only one case of the Southeast
      Asian HPFH deletion was found. This is the first detailed molecular
      epidemiological survey of thalassemia in the Chengdu region, Sichuan Province,
      People's Republic of China (PRC). 

PMID- 26290352
TI  - Red cell distribution width is associated with future risk of incident stroke.
      The Tromso Study.
AB  - Red cell distribution width (RDW), a measure of the variability in size of the
      circulating erythrocytes, is associated with cardiovascular morbidity and
      mortality. We aimed to investigate whether RDW was associated with incident
      stroke and case fatality in subjects recruited from the general population.
      Baseline characteristics were obtained from 25,992 subjects participating in the
      fourth survey of the Tromso Study, conducted in 1994/95. Incident stroke was
      registered from inclusion until December 31, 2010. Cox regression models were
      used to calculate hazard ratios (HR) with 95% confidence intervals (95% CI) for
      stroke, adjusted for age, sex, body mass index, smoking, haemoglobin level, white
      blood cell count, thrombocyte count, hypertension, total cholesterol,
      triglycerides, self-reported diabetes, and red blood cell count. During a median
      follow-up of 15.8 years, 1152 participants experienced a first-ever stroke. A 1%
      increment in RDW yielded a 13% higher risk of stroke (multivariable HR: 1.13, 95%
      CI: 1.07-1.20). Subjects with RDW in the highest quintile compared to the lowest
      had a 37% higher risk of stroke in multivariable analysis (HR: 1.37, 95% CI: 1.11
      1.69). Subjects with RDW above the 95-percentile had 55% higher risk of stroke
      compared to those in the lowest quintile (HR: 1.55, 95% CI: 1.16-2.06). All risk
      estimates remained unchanged after exclusion of subjects with anaemia (n=1102).
      RDW was not associated with increased risk of death within one year or during the
      entire follow-up after an incident stroke. RDW is associated with incident stroke
      in a general population, independent of anaemia and traditional atherosclerotic
      risk factors.

PMID- 26290353
TI  - Elevated synchrony in Parkinson disease detected with electroencephalography.
AB  - OBJECTIVE: Parkinson disease (PD) can be difficult to diagnose and treat.
      Development of a biomarker for PD would reduce these challenges by providing an
      objective measure of disease. Emerging theories suggest PD is characterized by
      excessive synchronization in the beta frequency band (~20Hz) throughout basal
      ganglia-thalamocortical loops. Recently we showed with invasive
      electrocorticography that one robust measure of this synchronization is the
      coupling of beta phase to broadband gamma amplitude (ie, phase-amplitude coupling
      [PAC]). Other recent work suggests that high-frequency activity is detectable at
      the scalp using electroencephalography (EEG). Motivated by these findings, we
      tested whether beta-gamma PAC over sensorimotor cortex, recorded noninvasively
      with EEG, differs between PD patients off and on medications, and healthy control
      subjects. METHODS: Resting EEG was compared from 15 PD patients and 16 healthy
      control subjects. PD patients were tested on and off medications on different
      days, in a counterbalanced order. For each data set we calculated PAC and
      compared results across groups. RESULTS: PAC was elevated in the patients off
      medications compared to on medications (p = 0.008) and for patients off
      medications compared to controls (p = 0.009). INTERPRETATION: Elevated PAC is
      detectable using scalp EEG in PD patients off medications compared to on
      medications, and compared to healthy controls. This suggests that EEG PAC may
      provide a noninvasive biomarker of the parkinsonian state. This biomarker could
      be used as a control signal for closed-loop control of deep brain stimulation
      devices, for adjustment of dopaminergic treatment, and also has the potential to
      aid in diagnosis.

PMID- 26290354
TI  - Genetic causal attribution of epilepsy and its implications for felt stigma.
AB  - OBJECTIVE: Research in other disorders suggests that genetic causal attribution
      of epilepsy might be associated with increased stigma. We investigated this
      hypothesis in a unique sample of families containing multiple individuals with
      epilepsy. METHODS: One hundred eighty-one people with epilepsy and 178 biologic
      relatives without epilepsy completed a self-administered survey. In people with
      epilepsy, felt stigma was assessed through the Epilepsy Stigma Scale (ESS),
      scored 1-7, with higher scores indicating more stigma and >4 indicating some felt
      stigma. Felt stigma related to having epilepsy in the family was assessed through
      the Family Epilepsy Stigma Scale (FESS), created by replacing "epilepsy" with
      "epilepsy in my family" in each ESS item. Genetic attribution was assessed
      through participants' perceptions of the (1) role of genetics in causing epilepsy
      in the family, (2) chance they had an epilepsy-related mutation, and (3) (in
      people with epilepsy) influence of genetics in causing their epilepsy. RESULTS:
      Among people with epilepsy, 22% met criteria for felt stigma (ESS score >4).
      Scores were increased among individuals who were aged >=60 years, were
      unemployed, reported epilepsy-related discrimination, or had seizures within the
      last year or >100 seizures in their lifetime. Adjusting for other variables, ESS
      scores in people with epilepsy were significantly higher among those who
      perceived genetics played a "medium" or "big" role in causing epilepsy in the
      family than in others (3.4 vs. 2.7, p = 0.025). Only 4% of relatives without
      epilepsy had felt stigma. Scores in relatives were unrelated to genetic
      attribution. SIGNIFICANCE: In these unusual families, predictors of felt stigma
      in individuals with epilepsy are similar to those in other studies, and stigma
      levels are low in relatives without epilepsy. Felt stigma may be increased in
      people with epilepsy who believe epilepsy in the family has a genetic cause,
      emphasizing the need for sensitive communication about genetics.

PMID- 26290355
TI  - Identification of recombinant human EPO variants in greyhound plasma and urine by
      ELISA, LC-MS/MS and western blotting: a comparative study.
AB  - The recombinant human erythropoietins epoetin alfa (Eprex(r)), darbepoetin
      (Aranesp(r)) and methoxy polyethylene glycol-epoetin beta (Mircera(r)) were
      administered to greyhounds for 7, 10 and 14 days respectively. Blood and urine
      samples were collected and analysed for erythropoietin by ELISA, LC-MS/MS and
      western blotting. Limits of confirmation in plasma for western blotting and LC
      MS/MS methods ranged from a low of 2.5mIU/mL, and closely matched the sensitivity
      of ELISA screening.

PMID- 26290356
TI  - Age-specific survival and annual variation in survival of female chamois differ
      between populations.
AB  - In many species, population dynamics are shaped by age-structured demographic
      parameters, such as survival, which can cause age-specific sensitivity to
      environmental conditions. Accordingly, we can expect populations with different
      age-specific survival to be differently affected by environmental variation.
      However, this hypothesis is rarely tested at the intra-specific level. Using
      capture-mark-recapture models, we quantified age-specific survival and the extent
      of annual variations in survival of females of alpine chamois in two sites. In
      one population, survival was very high (>0.94; Bauges, France) until the onset of
      senescence at approximately 7 years old, whereas the two other populations (Swiss
      National Park, SNP) had a later onset (12 years old) and a lower rate of
      senescence. Senescence patterns are therefore not fixed within species. Annual
      variation in survival was higher in the Bauges (SD = 0.26) compared to the SNP
      populations (SD = 0.20). Also, in each population, the age classes with the
      lowest survival also experienced the largest temporal variation, in accordance
      with inter-specific comparisons showing a greater impact of environmental
      variation on these age classes. The large difference between the populations in
      age-specific survival and variation suggests that environmental variation and
      climate change will affect these populations differently.

PMID- 26290357
TI  - Disposition of Extended Release Levetiracetam in Normal Healthy Dogs After Single
      Oral Dosing.
AB  - BACKGROUND: Levetiracetam is an anticonvulsant used for control of canine
      epilepsy. An extended release preparation should improve dosing convenience.
      OBJECTIVES: To determine the disposition of extended release levetiracetam in
      normal dogs after single dosing. ANIMALS: Pharmacokinetic study: 16 healthy,
      adult dogs. METHODS: Using a partially randomized crossover study, levetiracetam
      (30 mg/kg) was administered intravenously (i.v.) and orally (p.o.) as extended
      release preparation with or without food. Blood was collected for 24 hours (i.v.)
      or 36 hours (p.o.). Serum levetiracetam was quantitated by immunoassay and data
      were subjected to noncompartmental analysis. RESULTS: Pharmacokinetic parameters
      for fasted versus fed animals, respectively, were (mean +/- SEM): Cmax = 26.6 +/-
      2.38 and 30.7 +/- 2.88 MU/mL, Tmax = 204.3 +/- 18.9 and 393.8 +/- 36.6 minutes,
      t1/2 = 4.95 +/- 0.55 and 4.48 +/- 0.48 hours, MRT = 9.8 +/- 0.72 and 10 +/- 0.64
      hours, MAT = 4.7 +/- 0.38 and 5.6 +/- 0.67 hours, and F = 1.04 +/- 0.04 and 1.26
      +/- 0.07%. Significant differences were limited to Tmax (longer) and F (greater)
      in fed compared to fasted animals. Serum levetiracetam concentration remained
      above 5 MU/mL for approximately 20 hours in both fasted and fed animals.
      CONCLUSIONS AND CLINICAL IMPORTANCE: Extended release levetiracetam (30 mg/kg
      q12h), with or without food, should maintain concentrations above the recommended
      minimum human therapeutic concentration.

PMID- 26290358
TI  - Filamentous anoxygenic phototrophic bacteria from cyanobacterial mats of Alla hot
      springs (Barguzin Valley, Russia).
AB  - Alkaline hydrotherms of the Baikal rift zone are unique systems to study the
      diversity of thermophilic bacteria. In this study, we present data on the
      phototrophic bacterial community of cyanobacterial mats from the alkaline Alla
      hot spring. Using a clonal analysis approach, this study evaluated the species
      diversity, the proportion of oxygenic and anoxygenic phototrophs and their
      distribution between various areas of the spring. Novel group-specific PCR
      primers were designed and applied to detect representatives of the Chloroflexus
      and Roseiflexus genera in mat samples. For the first time, the presence of
      Roseiflexus-like bacteria was detected in the Baikal rift zone. 

PMID- 26290359
TI  - Identification and characterization of a thermostable bifunctional enzyme with
      phosphomannose isomerase and sugar-1-phosphate nucleotidylyltransferase
      activities from a hyperthermophilic archaeon, Pyrococcus horikoshii OT3.
AB  - Mannosylglycerate is known as a compatible solute, and plays important roles for
      salinity adaptation and high temperature stability of microorganisms. In the gene
      cluster for the mannosylglycerate biosynthetic pathway predicted from the genomic
      data of Pyrococcus horikoshii OT3, the PH0925 protein was found as a putative
      bifunctional enzyme with phosphomannose isomerase (PMI) and mannose-1-phosphate
      guanylyltransferase (Man-1-P GTase) activities, which can synthesize GDP-mannose
      when accompanied by a phosphomannomutase/phosphoglucomutase (PMM/PGM) enzyme
      (PH0923). The recombinant PH0925 protein, expressed in E. coli, exhibited both
      expected PMI and Man-1-P GTase activities, as well as absolute thermostability;
      95  degrees C was the optimum reaction temperature. According to the
      guanylyltransferase activity (GTase) of the PH0925 protein, it was found that the
      protein can catalyze glucose-1-phosphate (Glc-1-P) and glucosamine-1-phosphate
      (GlcN-1-P) in addition to Man-1-P. The analyses of C-terminus-truncated forms of
      the PH0925 protein indicated that sugar-1-phosphate nucleotidylyltransferase
      (Sugar-1-P NTase) activity was located in the region from the N-terminus to the
      345th residue, and that the C-terminal 114 residue region of the PH0925 protein
      inhibited the Man-1-P GTase activity. Conversely, the PMI activity was abolished
      by deletion of the C-terminal 14 residues. This is the first report of a
      thermostable enzyme with both PMI and multiple Sugar-1-P NTase activities. 

PMID- 26290360
TI  - False-negative rate of intraoperative frozen section margin analysis for complex
      head and neck nonmelanoma skin cancer excisions.
AB  - INTRODUCTION: Intraoperative frozen section analysis (IFSA) is traditionally
      performed for complex and high-risk non-melanoma skin cancer (NMSC) resections,
      particularly when surgery under a general anaesthetic and a complex
      reconstruction is required, and where Mohs micrographic surgery (MMS) is not
      available. METHODS: A retrospective audit of 253 cases between 1999 and 2009 was
      undertaken, investigating the accuracy and efficacy of IFSA for the treatment of
      NMSC in our tertiary skin tumour unit based in a university hospital setting.
      RESULTS: The combined incomplete and very narrow (<1 mm) excision margin rates
      were 28.7% and 27.5% for basal cell and squamous cell carcinoma, respectively.
      Unrepresentative sampling of the excision margins intraoperatively was the
      overwhelming cause of error (94%). CONCLUSION: After a thorough audit of our
      data, IFSA has been abandoned for the treatment of NMSC in our unit. MMS is
      practised intraoperatively, even in advanced cases. We believe that IFSA no
      longer has any role in our complex, multidisciplinary skin cancer practice.

PMID- 26290362
TI  - Counselling is difficult when outcomes are associated with mode of delivery and
      not with the plan for mode of delivery.

PMID- 26290361
TI  - Comparative two-dimensional polyacrylamide gel electrophoresis of the salivary
      proteome of children with autism spectrum disorder.
AB  - In the last decades, prevalence of autism spectrum disorder (ASD) has been on the
      rise. However, clear aetiology is still elusive and improvements in early
      diagnosis are needed. To uncover possible biomarkers present in ASD, we used two
      dimensional polyacrylamide gel electrophoresis and nanoliquid chromatography
      tandem mass spectrometry (nanoLC-MS/MS), to compare salivary proteome profiling
      of children with ASD and controls. A total of 889 spots were compared and only
      those spots with a fold change >=1.7 and a P-value <0.05 or a fold change of
      >=3.0 between ASD cases and controls were analysed by nanoLC-MS/MS. Alpha
      amylase, CREB-binding protein, p532, Transferrin, Zn alpha2 glycoprotein, Zymogen
      granule protein 16, cystatin D and plasminogen were down-regulated in ASD.
      Increased expression of proto-oncogene Frequently rearranged in advanced T-cell
      lymphomas 1 (FRAT1), Kinesin family member 14, Integrin alpha6 subunit, growth
      hormone regulated TBC protein 1, parotid secretory protein, Prolactin-inducible
      protein precursor, Mucin-16, Ca binding protein migration inhibitory factor
      related protein 14 (MRP14) was observed in individuals with ASD. Many of the
      identified proteins have previously been linked to ASD or were proposed as risk
      factors of ASD at the genetic level. Some others are involved in pathological
      pathways implicated in ASD causality such as oxidative stress, lipid and
      cholesterol metabolism, immune system disturbances and inflammation. These data
      could contribute to protein signatures for ASD presence, risk and subtypes, and
      advance understanding of ASD cause as well as provide novel treatment targets for
      ASD.

PMID- 26290363
TI  - RELATIONSHIP BETWEEN THE CORTICAL THICKNESS AND SERUM CORTISOL LEVELS IN DRUG
      NAIVE, FIRST-EPISODE PATIENTS WITH MAJOR DEPRESSIVE DISORDER: A SURFACE-BASED
      MORPHOMETRIC STUDY.
AB  - OBJECTIVE: In major depressive disorder (MDD) patients, higher morning cortisol
      levels due to a hyperactive hypothalamic-pituitary-adrenal (HPA) axis have been
      reported. The aim of the present study was to evaluate the relationship between
      cortical thinning and the serum cortisol levels during the first depressive
      episode in drug-naive MDD patients using an automated surface-based morphometry
      (SBM) method. METHODS: The institutional review board approved this prospective
      study. MR imaging data were obtained using a 3T scanner by a three-dimensional
      fast-spoiled gradient recalled acquisition with steady state (3D-FSPGR). Thirty
      drug-naive patients with MDD and 41 age- and gender-matched healthy subjects
      (controls) were enrolled. We then used the SBM method (Freesurfer) to generate
      cortical thickness maps, and measured the cortical thickness in each subject.
      Morning blood samples were drawn from all participants for cortisol measurements.
      RESULTS: We found the serum cortisol levels were significantly higher in the MDD
      patients than in the controls. The MDD patients manifested significant thinning
      of the left lateral orbitofrontal cortex compared with the controls. There was a
      significant negative linear correlation between the thickness of the left lateral
      orbitofrontal cortex and the serum cortisol levels in the MDD patients.
      CONCLUSIONS: In the early stage of MDD, the thickness of the lateral
      orbitofrontal cortex was significantly reduced, and also showed a significant
      inverse correlation with the serum cortisol levels. Since the lateral
      orbitofrontal cortex contains a high concentration of glucocorticoid receptor,
      glucocorticoid receptor-mediated signaling transductions could contribute to
      neurotoxicity, which might occur when there are high cortisol levels in patients
      with MDD.

PMID- 26290364
TI  - Metal diselenide nanoparticles as highly active and stable electrocatalysts for
      the hydrogen evolution reaction.
AB  - In this communication, nickel diselenide (NiSe2) nanoparticles are synthesized by
      a facile and low-cost hydrothermal method. The synthesis method can be extended
      to other metal diselenides as well. The electrode made of NiSe2 exhibits superior
      electrocatalytic activity in the hydrogen evolution reaction (HER). A low Tafel
      slope of 31.1 mV per decade is achieved for NiSe2, which is comparable to that of
      platinum (~30 mV per decade). Moreover, the catalytic activity of NiSe2 is very
      stable and no obvious degradation is found even after 1000 cyclic voltammetric
      sweeps. 

PMID- 26290366
TI  - Acute reactive oxygen species (ROS)-dependent effects of IL-1beta, TNF-alpha, and
      IL-6 on the glomerular filtration barrier (GFB) in vivo.
AB  - This study was performed to investigate the immediate actions of the
      proinflammatory cytokines IL-1beta, TNF-alpha, and IL-6 on the permeability of
      the glomerular filtration barrier (GFB) in rats and to test whether these actions
      are dependent upon the release of reactive oxygen species (ROS). In anesthetized
      rats, blood access was achieved and the left ureter was cannulated for urine
      collection. Rats were continuously infused intravenously with either IL-1beta
      (0.4 and 2 MUg.kg(-1).h(-1)), TNF-alpha (0.4 and 2 MUg.kg(-1).h(-1)), or IL-6 (4
      and 8 MUg.kg(-1).h(-1)), together with polydisperse FITC-Ficoll-70/400 and inulin
      for 1 h. Plasma and urine samples were analyzed by high performance size
      exclusion chromatography (HPSEC) for determination of glomerular sieving
      coefficients (theta). The glomerular filtration rate (GFR) was also assessed
      (51Cr-EDTA). In separate experiments, the superoxide scavenger tempol (30 mg.kg(
      1).h(-1)) was given before and during cytokine infusions. IL-1beta and TNF-alpha
      caused rapid, partly reversible increases in glomerular permeability to large
      molecules (Ficoll50-80A), peaking at 5-30 min, while IL-6 caused a more gradual
      increase in permeability, leveling off at 60 min. Tempol almost completely
      abrogated the glomerular permeability effects of the cytokines infused. In
      conclusion IL-1beta, TNF-alpha, and IL-6, when infused systemically, caused
      immediate and partly reversible increases in glomerular permeability, which could
      be inhibited by the superoxide scavenger tempol, suggesting an important role of
      ROS in acute cytokine-induced permeability changes in the GFB.

PMID- 26290365
TI  - Caregiving in Dementia and its Impact on Psychological Functioning and Health
      Related Quality of Life: Findings from a Colombian Sample.
AB  - Existing published studies about health-related quality of life (HRQOL) in
      caregivers of dementia patients living in Latin American countries are very
      limited. However, cultural aspects, personal values, and social structure may
      affect the way caregivers experience their role in different societies. The
      current study investigated the relationship between HRQOL and psychological
      factors using a cross-sectional design. The sample consisted of 102 informal
      caregivers of patients with dementia from Bogota, Colombia, South America.
      Measures included the Patient Health Questionnaire (PHQ-9) for depression, the
      Satisfaction with Life Scale (SWLS), the Zarit Burden Interview, and the Short
      Health Questionnaire (SF36) for HRQOL. Canonical correlations revealed that there
      was a significant relationship between caregivers' mental health and HRQOL, such
      that caregivers with better satisfaction with life and less symptoms of
      depression had more vitality and better general health. There is a strong
      relationship between mental health and health-related quality of life in
      Colombian caregivers of dementia patients living in their country of origin.
      Specific aspects of mental health, including satisfaction with life and
      depression, need to be addressed in order to improve caregivers' quality of life.
      Given that mental health care resources may be scarce in Latin American
      countries, culturally appropriate interventions should focus on
      preventing/treating depression and promote life satisfaction, as a way to improve
      their quality of life. 

PMID- 26290367
TI  - Characterization of the putative phosphorylation sites of the AQP2 C terminus and
      their role in AQP2 trafficking in LLC-PK1 cells.
AB  - Vasopressin (VP) stimulates a signaling cascade that results in phosphorylation
      and apical membrane accumulation of aquaporin-2 (AQP2), leading to water
      reabsorption by kidney collecting ducts. However, the roles of most C-terminal
      phosphorylation events in stimulated and constitutive AQP2 recycling are
      incompletely understood. Here, we generated LLC-PK1 cells containing point
      mutations of all potential phosphorylation sites in the AQP2 C terminus: S226,
      S229, T244, S256, S261, S264, and S269, to determine their impact on AQP2
      trafficking. We produced an All Null AQP2 construct in which these serine (S) or
      threonine (T) residues were mutated to alanine (A) or glycine (G), and we then
      reintroduced the phosphorylation mimic aspartic acid (D) individually to each
      site in the All Null mutant. As expected, the All Null mutant does not accumulate
      at the plasma membrane in response to VP but still undergoes constitutive
      recycling, as shown by its membrane accumulation when endocytosis is blocked by
      methyl-beta-cyclodextrin (MbetaCD), and accumulation in a perinuclear patch at
      low temperature (20 degrees C). Single phosphorylation mimics S226D, S229D,
      T244D, S261D, S264D, and S269D were insufficient to cause membrane accumulation
      of AQP2 alone or after VP treatment. However, AQP2 S256 reintroduced into the All
      Null mutant maintains its trafficking response to VP. We conclude that 1)
      constitutive recycling of AQP2 does not require phosphorylation at any C-terminal
      sites; 2) forced "phosphorylation" of sites in the AQP2 C terminus is
      insufficient to stimulate membrane accumulation in the absence of S256
      phosphorylation; and 3) phosphorylation of S256 alone is necessary and sufficient
      to cause membrane accumulation of AQP2. 

PMID- 26290369
TI  - Perspectives on edema in childhood nephrotic syndrome.
AB  - There have been two major theories surrounding the development of edema in
      nephrotic syndrome (NS), namely, the under- and overfill hypotheses. Edema is one
      of the cardinal features of NS and remains one of the principal reasons for
      admission of children to the hospital. Recently, the discovery that proteases in
      the glomerular filtrate of patients with NS are activating the epithelial sodium
      channel (ENaC), resulting in intrarenal salt retention and thereby contributing
      to edema, might suggest that targeting ENaC with amiloride might be a suitable
      strategy to manage the edema of NS. Other potential agents, particularly
      urearetics and aquaretics, might also prove useful in NS. Recent evidence also
      suggests that there may be other areas involved in salt storage, especially the
      skin, and it will be intriguing to study the implications of this in NS. 

PMID- 26290370
TI  - Hedgehog signaling indirectly affects tubular cell survival after obstructive
      kidney injury.
AB  - Hedgehog (Hh) is an evolutionary conserved signaling pathway that has important
      functions in kidney morphogenesis and adult organ maintenance. Recent work has
      shown that Hh signaling is reactivated in the kidney after injury and is an
      important mediator of progressive fibrosis. Pericytes and fibroblasts have been
      proposed to be the principal cells that respond to Hh ligands, and
      pharmacological attenuation of Hh signaling has been considered as a possible
      treatment for fibrosis, but the effect of Hh inhibition on tubular epithelial
      cells after kidney injury has not been reported. Using genetically modified mice
      in which tubule-derived hedgehog signaling is increased and mice in which this
      pathway is conditionally suppressed in pericytes that express the proteoglycan
      neuron glial protein 2 (NG2), we found that suppression of Hh signaling is
      associated with decreased macrophage infiltration and tubular proliferation but
      also increased tubular apoptosis, an effect that correlated with the reduction of
      tubular beta-catenin activity. Collectively, our data suggest a complex function
      of hedgehog signaling after kidney injury in initiating both reparative and
      proproliferative, prosurvival processes. 

PMID- 26290371
TI  - Architecture of the human renal inner medulla and functional implications.
AB  - The architecture of the inner stripe of the outer medulla of the human kidney has
      long been known to exhibit distinctive configurations; however, inner medullary
      architecture remains poorly defined. Using immunohistochemistry with segment
      specific antibodies for membrane fluid and solute transporters and other
      proteins, we identified a number of distinctive functional features of human
      inner medulla. In the outer inner medulla, aquaporin-1 (AQP1)-positive long-loop
      descending thin limbs (DTLs) lie alongside descending and ascending vasa recta
      (DVR, AVR) within vascular bundles. These vascular bundles are continuations of
      outer medullary vascular bundles. Bundles containing DTLs and vasa recta lie at
      the margins of coalescing collecting duct (CD) clusters, thereby forming two
      regions, the vascular bundle region and the CD cluster region. Although AQP1 and
      urea transporter UT-B are abundantly expressed in long-loop DTLs and DVR,
      respectively, their expression declines with depth below the outer medulla.
      Transcellular water and urea fluxes likely decline in these segments at
      progressively deeper levels. Smooth muscle myosin heavy chain protein is also
      expressed in DVR of the inner stripe and the upper inner medulla, but is sparsely
      expressed at deeper inner medullary levels. In rodent inner medulla, fenestrated
      capillaries abut CDs along their entire length, paralleling ascending thin limbs
      (ATLs), forming distinct compartments (interstitial nodal spaces; INSs); however,
      in humans this architecture rarely occurs. Thus INSs are relatively infrequent in
      the human inner medulla, unlike in the rodent where they are abundant. UT-B is
      expressed within the papillary epithelium of the lower inner medulla, indicating
      a transcellular pathway for urea across this epithelium. 

PMID- 26290368
TI  - Obesity-induced changes in kidney mitochondria and endoplasmic reticulum in the
      presence or absence of leptin.
AB  - We investigated obesity-induced changes in kidney lipid accumulation,
      mitochondrial function, and endoplasmic reticulum (ER) stress in the absence of
      hypertension, and the potential role of leptin in modulating these changes. We
      compared two normotensive genetic mouse models of obesity, leptin-deficient ob/ob
      mice and hyperleptinemic melanocortin-4 receptor-deficient mice (LoxTB MC4R-/-),
      with their respective lean controls. Compared with controls, ob/ob and LoxTB MC4R
      /- mice exhibit significant albuminuria, increased creatinine clearance, and high
      renal triglyceride content. Renal ATP levels were decreased in both obesity
      models, and mitochondria isolated from both models showed alterations that would
      lower mitochondrial ATP production. Mitochondria from hyperleptinemic LoxTB MC4R
      /- mice kidneys respired NADH-generating substrates (including palmitate) at
      lower rates due to an apparent decrease in complex I activity, and these
      mitochondria showed oxidative damage. Kidney mitochondria of leptin-deficient
      ob/ob mice showed normal rates of respiration with no evidence of oxidative
      damage, but electron transfer was partially uncoupled from ATP synthesis. A
      fourfold induction of C/EBP homologous protein (CHOP) expression indicated
      induction of ER stress in kidneys of hyperleptinemic LoxTB MC4R-/- mice. In
      contrast, ER stress was not induced in kidneys of leptin-deficient ob/ob mice.
      Our findings show that obesity, in the absence of hypertension, is associated
      with renal dysfunction in mice but not with major renal injury. Alterations to
      mitochondria that lower cellular ATP levels may be involved in obesity-induced
      renal injury. The type and severity of mitochondrial and ER dysfunction differs
      depending upon the presence or absence of leptin. 

PMID- 26290372
TI  - Human anti-alpha3(IV)NC1 antibody drug conjugates target glomeruli to resolve
      nephritis.
AB  - Current therapies to limit kidney disease progression lack specificity and often
      have systemic toxicity. To approach this problem, we postulated that a human
      monoclonal antibody (F1.1), directed against the noncollagenous-1 domain (NC1) of
      alpha3(IV) collagen that localizes in glomeruli, could serve as a vehicle for
      targeted drug delivery. Given enhanced exposure of the NC1 domain of alpha3(IV)
      during glomerular diseases, with limited epitope expression in other organs,
      alpha3(IV)NC1 provides an ideal target for delivery of disease-modifying agents.
      As a potential disease-modifying agent, we initially took advantage of recent
      observations that PGE2 promoted recovery after established injury during the
      course of nephrotoxic nephritis. To address the general applicability of the
      approach, the efficacy of glomerular delivery of dexamethasone was also examined.
      To achieve glomerular targeted therapy, PGE2 and dexamethasone were coupled to
      F1.1. After confirmation of the composition and activity of the conjugates, both
      glomerular localization and the capacity of the conjugates to modify disease were
      evaluated. After injection into mice with established nephritis, resolution of
      disease was enhanced with both agents, with normalization of histology and
      improved blood urea nitrogen levels in conjugate-treated mice compared with
      untreated mice. The results provide a novel means of targeting glomeruli during
      nephritis, irrespective of cause, by providing efficient drug delivery, with the
      potential of limiting systemic effects. 

PMID- 26290373
TI  - A TRPM4-dependent current in murine renal primary cilia.
AB  - Defects in primary cilia lead to a variety of human diseases. One of these,
      polycystic kidney disease, can be caused by defects in a Ca2+-gated ion channel
      (TRPP2) found on the cilium. Other ciliary functions also contribute to
      cystogenesis, and defects in apical Ca2+ homeostasis have been implicated. By
      recording directly from the native cilia of mIMCD-3 cells, a murine cell line of
      renal epithelial origin, we have identified a second Ca2+-gated channel in the
      ciliary membrane: the transient receptor potential cation channel, subfamily M,
      member 4 (TRPM4). In excised primary cilia, TRPM4 was found to have a low
      sensitivity to Ca2+, with an EC50 of 646 MUM at +100 mV. It was inhibited by
      MgATP and by 9-phenanthrol. The channel was not permeable to Ca2+ or Cl- and had
      a permeability ratio PK/PNa of 1.42. Reducing the expression of Trpm4 mRNA with
      short hairpin (sh) RNA reduced the TRPM4 current by 87% and shortened primary
      cilia by 43%. When phospholipase C was inhibited, the sensitivity to cytoplasmic
      Ca2+ greatly increased (EC50 = 26 MUM at +100 mV), which is consistent with
      previous reports that phosphatidylinositol 4,5-bisphosphate (PIP2) modulates the
      channel. MgATP did not restore the channel to a preinactivation state, suggesting
      that the enzyme or substrate necessary for making PIP2 is not abundant in primary
      cilia of mIMCD-3 cells. The function of TRPM4 in renal primary cilia is not yet
      known, but it is likely to influence the apical Ca2+ dynamics of the cell,
      perhaps in tandem with TRPP2.

PMID- 26290374
TI  - Dopamine D2 receptors' effects on renal inflammation are mediated by regulation
      of PP2A function.
AB  - Lack or downregulation of the dopamine D2 receptor (D2R) results in increased
      renal expression of injury markers and proinflammatory factors that is
      independent of a blood pressure increase. This study aimed to determine the
      mechanisms involved in the regulation of renal inflammation by D2Rs. Silencing
      D2Rs in mouse renal proximal tubule cells increased the expression of the
      proinflammatory TNF-alpha, monocyte chemoattractant protein-1 (MCP-1), and IL-6.
      D2R downregulation also increased Akt phosphorylation and activity, and glycogen
      synthase kinase-3beta (GSK3beta) phosphorylation and cyclin D1 expression,
      downstream targets of Akt; however. phosphatidylinositol 3-kinase (PI3K) activity
      was not affected. Conversely, D2R stimulation decreased Akt and GSK3beta
      phosphorylation and cyclin D1 expression. Increased phospho-Akt, in the absence
      of increased PI3K activity, may result from decreased Akt dephosphorylation.
      Inhibition of protein phosphatase 2A (PP2A) with okadaic acid reproduced the
      effects of D2R downregulation on Akt, GSK3beta, and cyclin D1. The PP2A catalytic
      subunit and regulatory subunit PPP2R2C coimmunoprecipitated with the D2R. Basal
      phosphatase activity and the expression of PPP2R2C were decreased by D2R
      silencing that also blunted the increase in phosphatase activity induced by D2R
      stimulation. Similarly, silencing PPP2R2C also increased the phosphorylation of
      Akt and GSK3beta. Moreover, downregulation of PPP2R2C resulted in increased
      expression of TNF-alpha, MCP-1, and IL-6, indicating that decreased phosphatase
      activity may be responsible for the D2R effect on inflammatory factors. Indeed,
      the increase in NF-kappaB reporter activity induced by D2R silencing was blunted
      by increasing PP2A activity with protamine. Our results show that D2R controls
      renal inflammation, at least in part, by modulation of the Akt pathway through
      effects on PP2A activity/expression. 

PMID- 26290377
TI  - Complications associated with secondary orbital implantations.
AB  - PURPOSE: To evaluate complications associated with secondary procedures for
      orbital implants. METHODS: A retrospective review was made of the records of
      patients who had undergone a secondary orbital implantation at a tertiary
      referral centre at St Erik Eye Hospital in Stockholm, Sweden, from 1998 up to and
      including the first half of 2009. Implant-related complications were noted as was
      demographic and surgical background data. The regional ethics committee in
      Stockholm gave its approval for this study. RESULTS: Seventy-one patients had
      received a secondary orbital implant at the eye hospital. Implant-related
      complications were noted in 24 patients (34%), and 20 patients required
      reoperation/s (28%). There were five types of complications: migration of the
      implant (13%), insufficient orbital volume (10%), exposure/extrusion/infection
      (8%), mechanical obstruction (1%) and socket oedema (1%). Analyses of sizes and
      types of implants, wrapping and surgical techniques did not reveal any specific
      factor that resulted in an increased number of complications. However, there was
      an indication that aluminium oxide might be associated with fewer complications
      (2/11 = 18%). CONCLUSION: Our results show that secondary orbital implantations
      have high complication rates and that further surgery is needed in more than a
      quarter of cases. It is important to consider these facts when planning to insert
      secondary implants and to provide patients with accurate information about the
      procedure and possible outcomes.

PMID- 26290375
TI  - No effect of albumin infusion on the prevention of hepatic encephalopathy after
      transjugular intrahepatic portosystemic shunt.
AB  - Hepatic encephalopathy (HE) is a major problem in patients submitted to TIPS.
      Previous studies identified low albumin as a factor associated to post-TIPS HE.
      In cirrhotics with diuretic-induced HE and hypovolemia, albumin infusion reduced
      plasma ammonia and improved HE. Our aim was to evaluate if the incidence of overt
      HE (grade II or more according to WH) and the modifications of venous blood
      ammonia and psychometric tests during the first month after TIPS can be prevented
      by albumin infusion. Twenty-three patients consecutively submitted to TIPS were
      enrolled and treated with 1 g/Kg BW of albumin for the first 2 days after TIPS
      followed by 0,5 g/Kg BW at day 4th and 7th and then once a week for 3 weeks.
      Forty-five patients included in a previous RCT (Riggio et al. 2010) followed with
      the same protocol and submitted to no pharmacological treatment for the
      prevention of HE, were used as historical controls. No differences in the
      incidence of overt HE were observed between the group of patients treated with
      albumin and historical controls during the first month (34 vs 31 %) or during the
      follow-up (39 vs 48 %). Two patients in the albumin group and three in historical
      controls needed the reduction of the stent diameter for persistent HE. Venous
      blood ammonia levels and psychometric tests were also similarly modified in the
      two groups. Survival was also similar. Albumin infusion has not a role in the
      prevention of post-TIPS HE.

PMID- 26290379
TI  - Demonstrating the clinical pharmacist's activity: validation of an intervention
      oriented classification system.
AB  - BACKGROUND: Clinical pharmacists are increasingly involved in detecting and
      solving drug-related problems. To document their performance, a convenient tool
      to code pharmaceutical interventions in daily practice is desirable. The Swiss
      Society of Public Health Administration and Hospital Pharmacists (GSASA) proposed
      to implement a new classification system for pharmaceutical interventions.
      OBJECTIVES: To develop and validate a classification system for pharmaceutical
      interventions and to compare it with the well-established Pharmaceutical Care
      Network Europe (PCNE) system. SETTING: Rehabilitation clinic, geriatric and
      orthopaedic wards of a 427-bed teaching hospital. METHODS: Development of the
      GSASA classification started with expert panel discussions and the validation of
      the first version (GSASA V1). To assess appropriateness, interpretability, and
      validity, clinical pharmacists documented during a 6-week period all
      interventions using GSASA V1 and PCNE version 6.2 (V6.2). Acceptability and
      feasibility were tested by an 8-item questionnaire with 5-point Likert scale (1 =
      strongly disagree, 5 = strongly agree), and inter-rater reliability (Fleiss-Kappa
      coefficients kappa) was determined. After revision, the second version (V2) was
      assessed again for reliability. MEAN OUTCOME MEASURES: User's
      agreement/satisfaction, comprehensiveness/reliability of the classification
      system. RESULTS: The GSASA V1 includes 4 categories and 35 subcategories. Of 115
      interventions classified with GSASA V1, 93 (80.9 %) could be completely
      classified in all categories. This explains that 3 of 6 users could be not
      satisfied with the comprehensiveness of GSASA V1 (mean user agreement 2.7 +/-
      0.8). The questionnaire showed that all users could find GSASA V1 (4.0 +/- 0.0)
      easier to use than PCNE V6.2 (3.0 +/- 0.9). Users were generally satisfied with
      the GSASA V1 (3.5 +/- 0.8), especially with the adequate time expenditure (4.0 +/
      0.7). Inter-rater reliability and acceptability of GSASA V1 were comparable to
      those of the PCNE V6.2. The agreement among the GSASA V1 users was substantial
      for the categories 'problem' (kappa = 0.66), 'intervention' (kappa = 0.74), and
      'outcome' (kappa = 0.63), while moderate agreement for the category 'cause' was
      obtained (kappa = 0.53). The final system GSASA V2 includes 5 categories
      (addition of 'type of problem') and 41 subcategories. Total inter-rater
      reliability was moderate (kappa = 0.52). CONCLUSION: The GSASA classification
      system appeared to be reliable and promising for documentation of pharmaceutical
      interventions in daily practice (practical and less time-consuming). The system
      is validated in terms of appropriateness, interpretability, validity,
      acceptability, feasibility, and reliability.

PMID- 26290378
TI  - Phenylphenalenones protect banana plants from infection by Mycosphaerella
      fijiensis and are deactivated by metabolic conversion.
AB  - Phenylphenalenones, polycyclic aromatic natural products from some
      monocotyledonous plants, are known as phytoalexins in banana (Musa spp.). In this
      study, (1) H nuclear magnetic resonance (NMR)-based metabolomics along with
      liquid chromatography and mass spectrometry were used to explore the chemical
      responses of the susceptible 'Williams' and the resistant 'Khai Thong Ruang' Musa
      varieties to the ascomycete fungus Mycosphaerella fijiensis, the agent of the
      black leaf Sigatoka disease. Principal component analysis discriminated strongly
      between infected and non-infected plant tissue, mainly because of specialized
      metabolism induced in response to the fungus. Phenylphenalenones are among the
      major induced compounds, and the resistance level of the plants was correlated
      with the progress of the disease. However, a virulent strain of M. fijiensis was
      able to overcome plant resistance by converting phenylphenalenones to sulfate
      conjugates. Here, we report the first metabolic detoxification of fungitoxic
      phenylphenalenones to evade the chemical defence of Musa plants. 

PMID- 26290380
TI  - Comparison of Deconvolution-Based and Absorption Modeling IVIVC for Extended
      Release Formulations of a BCS III Drug Development Candidate.
AB  - In vitro-in vivo correlations (IVIVC) are predictive mathematical models
      describing the relationship between dissolution and plasma concentration for a
      given drug compound. The traditional deconvolution/convolution-based approach is
      the most common methodology to establish a level A IVIVC that provides point to
      point relationship between the in vitro dissolution and the in vivo input rate.
      The increasing application of absorption physiologically based pharmacokinetic
      model (PBPK) has provided an alternative IVIVC approach. The current work
      established and compared two IVIVC models, via the traditional
      deconvolution/convolution method and via absorption PBPK modeling, for two types
      of modified release (MR) formulations (matrix and multi-particulate tablets) of
      MK-0941, a BCS III drug development candidate. Three batches with distinct
      release rates were studied for each formulation technology. A two-stage linear
      regression model was used for the deconvolution/convolution approach while
      optimization of the absorption scaling factors (a model parameter that relates
      permeability and input rate) in Gastroplus(TM) Advanced Compartmental Absorption
      and Transit model was used for the absorption PBPK approach. For both types of
      IVIVC models established, and for either the matrix or the multiparticulate
      formulations, the average absolute prediction errors for AUC and C max were below
      10% and 15%, respectively. Both the traditional deconvolution/convolution-based
      and the absorption/PBPK-based level A IVIVC model adequately described the
      compound pharmacokinetics to guide future formulation development. This case
      study highlights the potential utility of absorption PBPK model to complement the
      traditional IVIVC approaches for MR products. 

PMID- 26290381
TI  - Tetraspanin-3 is an organizer of the multi-subunit Nogo-A signaling complex.
AB  - To ensure precision and specificity of ligand-receptor-induced signaling, co
      receptors and modulatory factors play important roles. The membrane-bound ligand
      Nogo-A (an isoform encoded by RTN4) induces inhibition of neurite outgrowth, cell
      spreading, adhesion and migration through multi-subunit receptor complexes. Here,
      we identified the four-transmembrane-spanning protein tetraspanin-3 (TSPAN3) as a
      new modulatory co-receptor for the Nogo-A inhibitory domain Nogo-A-Delta20.
      Single-molecule tracking showed that TSPAN3 molecules in the cell membrane
      reacted to binding of Nogo-A with elevated mobility, which was followed by
      association with the signal-transducing Nogo-A receptor sphingosine-1-phosphate
      receptor 2 (S1PR2). Subsequently, TSPAN3 was co-internalized as part of the Nogo
      A-ligand-receptor complex into early endosomes, where it subsequently separated
      from Nogo-A and S1PR2 to be recycled to the cell surface. The functional
      importance of the Nogo-A-TSPAN3 interaction is shown by the fact that knockdown
      of TSPAN3 strongly reduced the Nogo-A-induced S1PR2 clustering, RhoA activation,
      cell spreading and neurite outgrowth inhibition. In addition to the modulatory
      functions of TSPAN3 on Nogo-A-S1PR2 signaling, these results illustrate the very
      dynamic spatiotemporal reorganizations of membrane proteins during ligand-induced
      receptor complex organization. 

PMID- 26290383
TI  - Erratum to: CT of inferior vena cava filters: normal presentations and potential
      complications.

PMID- 26290382
TI  - PDGFRbeta and oncogenic mutant PDGFRalpha D842V promote disassembly of primary
      cilia through a PLCgamma- and AURKA-dependent mechanism.
AB  - Primary cilia are microtubule-based sensory organelles projecting from most
      quiescent mammalian cells, which disassemble in cells cultured in serum-deprived
      conditions upon re-addition of serum or growth factors. Platelet-derived growth
      factors (PDGF) are implicated in deciliation, but the specific receptor isoforms
      and mechanisms involved are unclear. We report that PDGFRbeta promotes
      deciliation in cultured cells and provide evidence implicating PLCgamma and
      intracellular Ca(2+) release in this process. Activation of wild-type PDGFRalpha
      alone did not elicit deciliation. However, expression of constitutively active
      PDGFRalpha D842V mutant receptor, which potently activates PLCgamma (also known
      as PLCG1), caused significant deciliation, and this phenotype was rescued by
      inhibiting PDGFRalpha D842V kinase activity or AURKA. We propose that PDGFRbeta
      and PDGFRalpha D842V promote deciliation through PLCgamma-mediated Ca(2+) release
      from intracellular stores, causing activation of calmodulin and AURKA-triggered
      deciliation. 

PMID- 26290384
TI  - Effect of increasing the flip angle during the hepatocyte phase of gadobenate
      dimeglumine-enhanced 1.5T MRI in cirrhotic patients with hepatocellular
      carcinoma.
AB  - PURPOSE: To evaluate the effects of increasing the flip angle during the
      hepatocyte phase of gadobenate dimeglumine-enhanced magnetic resonance imaging
      (MRI) in cirrhotic patients with hepatocellular carcinoma (HCC). MATERIALS AND
      METHODS: Sixty-three patients with liver cirrhosis underwent gadobenate
      dimeglumine-enhanced 1.5T MRI with 90-minute delayed hepatocyte phase with flip
      angles of 10 degrees , 20 degrees , 30 degrees , consecutively. Relative
      enhancement and signal-to-noise ratio (SNR) of liver parenchyma at hepatocyte
      phase according to flip angle were calculated. The liver-to-lesion (low signal
      intensity HCCs, n = 63; >=1 cm) and contrast-to-noise ratio (CNR) at the
      hepatocyte phase according to flip angle were calculated. Two radiologists
      independently assessed the presence of HCCs using a 5-point scale, and detection
      sensitivity of HCCs was calculated according to flip angle. RESULTS: The relative
      enhancement of hepatic parenchyma differed significantly according to flip angle
      (10 degrees , mean relative enhancement = 0.69 +/- 0.46; 20 degrees , mean
      relative enhancement = 0.63 +/- 0.47; 30 degrees , mean relative enhancement =
      0.49 +/- 0.45; P = 0.043). The SNR of hepatic parenchyma was significantly
      different according to flip angle (10 degrees , mean SNR = 26.2 +/- 5.6; 20
      degrees , mean SNR = 25.3 +/- 5.7; 30 degrees , mean SNR = 22.8 +/- 6.1; P =
      0.004). The CNR of lesion was not significantly different according to flip angle
      (10 degrees , mean CNR = 7.5 +/- 6.6; 20 degrees , mean CNR = 10.2 +/- 6.9; 30
      degrees , mean CNR = 10.1 +/- 7.1; P = 0.051). The sensitivities with 10 degrees 
      and 20 degrees  for HCCs were significantly higher than those with 30 degrees 
      for one reader (P < 0.05). CONCLUSION: In patients with cirrhosis, hepatocyte
      phase gadobenate dimeglumine-enhanced 1.5T MRI with 20 degrees  flip angle should
      be recommended rather than 10 degrees  and 30 degrees  flip angle.

PMID- 26290386
TI  - Six-year incidence of visually significant age-related cataract: the Chennai eye
      disease incidence study.
AB  - BACKGROUND: The aim of this study is to report the 6-year incidence of age
      related cataract in a population-based study. DESIGN: The design used is a
      population-based cohort study. PARTICIPANTS: A cohort of 2484 phakic subjects,
      aged 40 years and above at baseline, from a south Indian population was included
      in the study. METHODS: Bilateral phakics with visual acuity of 6/12 or better and
      cataract less than N2, C2 and P2 on the Lens Opacities Classification System II
      at baseline were included. Subjects with glaucoma and corneal or retinal diseases
      were excluded. Incident visually significant cataract was defined as visual
      acuity of less than 6/18 with a corresponding one grade or greater change in Lens
      Opacities Classification System II or history of having undergone cataract
      surgery with evidence of pseudophakia or aphakia at the 6-year follow-up. MAIN
      OUTCOME MEASURES: Six-year incidence of visually significant cataract and
      associated risk factors data were collected. RESULTS: Incident visually
      significant cataract at 6 years was seen in 158 subjects (6.36%, 95% CI: 5.40
      7.32, phakics:pseudophakics/aphakics 70:88). Incidence was higher in the rural
      cohort as compared with the urban cohort (P < 0.001). Incidence increased with
      age and was highest in the >=70 years age group (odds ratio (OR):31.23, 95% CI:
      15.20-64.16, P < 0.001). Other associated risk factors included illiteracy (OR
      1.75, 95% CI: 1.17-2.61, P = 0.007) and smoking (OR 1.77, 95% CI: 1.08-2.88, P =
      0.02). CONCLUSIONS: A significant proportion of the population developed visually
      significant age-related cataract at 6 years. Incident visually significant
      cataract was significantly greater for the rural cohort between 50 and 69 years
      old.

PMID- 26290389
TI  - Skin Care in Organ Transplant Patients Europe Meeting Report from Annual Meeting,
      Leiden, The Netherlands, 15-18 May 2014.

PMID- 26290387
TI  - Skin Disease in Laminopathy-Associated Premature Aging.
AB  - The nuclear lamina, a protein network located under the nuclear membrane, has
      during the past decade found increasing interest due to its significant
      involvement in a range of genetic diseases, including the segmental premature
      aging syndromes Hutchinson-Gilford progeria syndrome, restrictive dermopathy, and
      atypical Werner syndrome. In this review we examine these diseases, some caused
      by mutations in the LMNA gene, and their skin disease features. Advances within
      this area might also provide novel insights into the biology of skin aging, as
      recent data suggest that low levels of progerin are expressed in unaffected
      individuals and these levels increase with aging. 

PMID- 26290391
TI  - Realizing up-conversion fluorescence tuning in lanthanide-doped nanocrystals by
      femtosecond pulse shaping method.
AB  - The ability to tune color output of nanomaterials is very important for their
      applications in laser, optoelectronic device, color display and multiplexed
      biolabeling. Here we first propose a femtosecond pulse shaping technique to
      realize the up-conversion fluorescence tuning in lanthanide-doped nanocrystals
      dispersed in the glass. The multiple subpulse formation by a square phase
      modulation can create different excitation pathways for various up-conversion
      fluorescence generations. By properly controlling these excitation pathways, the
      multicolor up-conversion fluorescence can be finely tuned. This color tuning by
      the femtosecond pulse shaping technique is realized in single material by single
      color laser field, which is highly desirable for further applications of the
      lanthanide-doped nanocrystals. This femtosecond pulse shaping technique opens an
      opportunity to tune the color output in the lanthanide-doped nanocrystals, which
      may bring a new revolution in the control of luminescence properties of
      nanomaterials. 

PMID- 26290392
TI  - Human cell dedifferentiation in mesenchymal condensates through controlled
      autophagy.
AB  - Tissue and whole organ regeneration is a dramatic biological response to injury
      that occurs across different plant and animal phyla. It frequently requires the
      dedifferentiation of mature cells to a condensed mesenchymal blastema, from which
      replacement tissues develop. Human somatic cells cannot regenerate in this way
      and differentiation is considered irreversible under normal developmental
      conditions. Here, we sought to establish in vitro conditions to mimic blastema
      formation by generating different three-dimensional (3D) condensates of human
      mesenchymal stromal cells (MSCs). We identified specific 3D growth environments
      that were sufficient to dedifferentiate aged human MSCs to an early mesendoderm
      like state with reversal of age-associated cell hypertrophy and restoration of
      organized tissue regenerating capacity in vivo. An optimal auophagic response was
      required to promote cytoplasmic remodeling, mitochondrial regression, and a
      bioenergetic shift from oxidative phosphorylation to anaerobic metabolism. Our
      evidence suggests that human cell dedifferentiation can be achieved through
      autonomously controlled autophagic flux. 

PMID- 26290393
TI  - Chemopreventive Effects of Dietary Eicosapentaenoic Acid Supplementation in
      Experimental Myeloid Leukemia.
AB  - Current therapies for treatment of myeloid leukemia do not eliminate leukemia
      stem cells (LSC), leading to disease relapse. In this study, we supplemented mice
      with eicosapentaenoic acid (EPA, C20:5), a polyunsaturated omega-3 fatty acid, at
      pharmacologic levels, to examine whether the endogenous metabolite,
      cyclopentenone prostaglandin delta-12 PGJ3 (Delta(12)-PGJ3), was effective in
      targeting LSCs in experimental leukemia. EPA supplementation for 8 weeks resulted
      in enhanced endogenous production of Delta(12)-PGJ3 that was blocked by
      indomethacin, a cyclooxygenase (COX) inhibitor. Using a murine model of chronic
      myelogenous leukemia (CML) induced by bone marrow transplantation of BCR-ABL
      expressing hematopoietic stem cells, mice supplemented with EPA showed a decrease
      in the LSC population, and reduced splenomegaly and leukocytosis, when compared
      with mice on an oleic acid diet. Supplementation of CML mice carrying the T315I
      mutation (in BCR-ABL) with EPA resulted in a similar effect. Indomethacin blocked
      the EPA effect and increased the severity of BCR-ABL-induced CML and decreased
      apoptosis. Delta(12)-PGJ3 rescued indomethacin-treated BCR-ABL mice and decreased
      LSCs. Inhibition of hematopoietic-prostaglandin D synthase (H-PGDS) by HQL-79 in
      EPA-supplemented CML mice also blocked the effect of EPA. In addition, EPA
      supplementation was effective in a murine model of acute myeloid leukemia. EPA
      supplemented mice exhibited a decrease in leukemia burden and a decrease in the
      LSC colony-forming unit (LSC-CFU). The decrease in LSCs was confirmed through
      serial transplantation assays in all disease models. The results support a
      chemopreventive role for EPA in myeloid leukemia, which is dependent on the
      ability to efficiently convert EPA to endogenous COX-derived prostanoids,
      including Delta(12)-PGJ3.

PMID- 26290394
TI  - Targeted DNA Methylation Screen in the Mouse Mammary Genome Reveals a Parity
      Induced Hypermethylation of Igf1r That Persists Long after Parturition.
AB  - The most effective natural prevention against breast cancer is an early first
      full-term pregnancy. Understanding how the protective effect is elicited will
      inform the development of new prevention strategies. To better understand the
      role of epigenetics in long-term protection, we investigated parity-induced DNA
      methylation in the mammary gland. FVB mice were bred or remained nulliparous and
      mammary glands harvested immediately after involution (early) or 6.5 months
      following involution (late), allowing identification of both transient and
      persistent changes. Targeted DNA methylation (109 Mb of Ensemble regulatory
      features) analysis was performed using the SureSelectXT Mouse Methyl-seq assay
      and massively parallel sequencing. Two hundred sixty-nine genes were
      hypermethylated and 128 hypomethylated persistently at both the early and late
      time points. Pathway analysis of the persistently differentially methylated genes
      revealed Igf1r to be central to one of the top identified signaling networks, and
      Igf1r itself was one of the most significantly hypermethylated genes.
      Hypermethylation of Igf1r in the parous mammary gland was associated with a
      reduction of Igf1r mRNA expression. These data suggest that the IGF pathway is
      regulated at multiple levels during pregnancy and that its modification might be
      critical in the protective role of pregnancy. This supports the approach of
      lowering IGF action for prevention of breast cancer, a concept that is currently
      being tested clinically.

PMID- 26290395
TI  - Hepatitis B Virus Combo Mutations Improve the Prediction and Active Prophylaxis
      of Hepatocellular Carcinoma: A Clinic-Based Cohort Study.
AB  - We aimed to evaluate whether hepatitis B virus (HBV) mutations at the core
      promoter region could improve the prediction and specific prophylaxis of
      hepatocellular carcinoma (HCC) in chronic HBV-infected patients. A total of 2,114
      HBV-infected patients enrolled between August 1998 and December 2007 were
      followed-up for 18,406 person-years. Of those, 612 received >=48 week treatments
      with nucleos(t)ide analogue (NA) and/or IFNalpha. Baseline HBV mutations were
      identified by sequencing. Propensity score matching was applied to reduce
      baseline differences between antiviral and control cohorts. Multivariate Cox
      regression analyses, including baseline characteristics of 2,114 patients, showed
      that age, male, cirrhosis, and HBV mutations (C1653T, T1753V, and A1762T/G1764A)
      independently increased HCC risk. In control patients carrying A1762T/G1764A,
      addition of C1653T and/or T1753V significantly increased HCC risk (HR, 1.57; P =
      0.038); combo mutations with C1653T, T1753V, and A1762T/G1764A improved the
      validity of HCC prediction by age, male, and cirrhosis (P = 0.002). In the
      matched cohorts, antiviral treatment reduced HCC incidence (13.90/1,000 vs.
      7.70/1,000 person-years, P = 0.005); NA treatment for >=60 months was required
      for the prophylaxis of HCC in cirrhotic patients (P = 0.03); antiviral treatment
      reduced HCC risk in patients carrying A1762T/G1764A (HR, 0.40; P = 0.002) or
      C1653T (HR, 0.45; P = 0.04) and in those without T1753V (HR, 0.42; P = 0.005),
      but could not reduce HCC risk in patients without A1762T/G1764A or C1653T and in
      those with T1753V. In summary, HBV mutation A1762T/G1764A, C1653T, and T1753V in
      combination improve HCC prediction in HBV-infected patients. To prevent HCC,
      patients infected with HBV carrying A1762T/G1764A or C1653T, but not T1753V,
      should be given priority of receiving antiviral treatments.

PMID- 26290396
TI  - Autologous platelet-rich fibrin in treatment of scleroderma ulcer.

PMID- 26290397
TI  - Paranoid thinking, cognitive bias and dangerous neighbourhoods: Implications for
      perception of threat and expectations of victimisation.
AB  - BACKGROUND: Paranoid thinking is prevalent in the non-clinical population and
      cognitive mechanisms of heuristic reasoning and jumping to conclusions bias
      contributes to its formation and maintenance. AIMS: This study investigated the
      degree to which paranoia, perceived environmental risk, heuristic reasoning and
      jumping to conclusions bias (measured with the beads task) contribute to
      misinterpretation of neutral stimuli, and whether this informed judgements
      regarding vulnerability to threat and crime. It is also investigated whether
      impulsiveness is a confounding factor on the beads task. METHODS: Two hundred
      participants were recruited using a snowball-sampling method for a quantitative
      cross-sectional study. Participants reported demographic information, three
      psychometric questionnaires and two experimental tasks via an online paradigm
      hosted by the Bristol Online Survey tool. RESULTS: Participants with high
      paranoia scores perceived their environment to be more dangerous than those with
      low scores. Participants with high paranoia scores also overestimated threat in
      neutral stimuli and had high expectations of future victimisation. Jumping to
      conclusions on the beads task did not predict fear of crime outcomes, but was
      predicted by impulsivity. CONCLUSION: Participants who demonstrated paranoid
      thinking were more likely to reside in perceived dangerous neighbourhoods and
      overestimate threat. While this could indicate a paranoid heuristic, it is a
      potentially rational response to prior experiences of crime and victimisation.
      Implications and suggestions for future research are discussed.

PMID- 26290398
TI  - Stereotactic body radiation therapy for a new lung cancer arising after
      pneumonectomy: dosimetric evaluation and pulmonary toxicity.
AB  - OBJECTIVE: To evaluate the tolerance of stereotactic body radiation therapy
      (SBRT) for the treatment of secondary lung tumours in patients who underwent
      previous pneumonectomy. METHODS: 12 patients were retrospectively analysed. The
      median maximum tumour diameter was 2.1 cm (1-4.5 cm). The median planning target
      volume was 20.7 cm(3) (2.4-101.2 cm(3)). Five patients were treated with a single
      fraction of 26 Gy and seven patients with fractionated schemes (3 * 10 Gy, 4 * 10
      Gy, 4 * 12 Gy). Lung toxicity, correlated with volume (V) of lung receiving >5,
      >10 and >20 Gy, local control and survival rate were assessed. Median follow-up
      was 28 months. RESULTS: None of the patients experienced pulmonary toxicity >
      grade 2 at the median dosimetric lung parameters of V5, V10 and V20 of 23.1%
      (range 10.7-56.7%), 7.3% (2.2-27.2%) and 2.7% (0.7-10.9%), respectively. No
      patients required oxygen or had deterioration of the performance status during
      follow-up if not as a result of clinical progression of disease. The local
      control probability at 2 years was 64.5%, and the overall survival at 2 years was
      80%. CONCLUSION: SBRT appears to be a safe and effective modality for treating
      patients with a second lung tumour after pneumonectomy. ADVANCES IN KNOWLEDGE:
      Our results and similar literature results show that when keeping V5, V10 V20
      <50%, <20% and <7%, respectively, the risk of significant lung toxicity is
      acceptable. Our experience also shows that biologically effective dose 10 >100
      Gy, necessary for high local control rate, can be reached while complying with
      the dose constraints for most patients.

PMID- 26290400
TI  - Epidemiology of Methicillin-Susceptible Staphylococcus aureus in a Neonatology
      Ward.
AB  - OBJECTIVE: In-hospital transmission of methicillin-susceptible Staphylococcus
      aureus (MSSA) among neonates remains enigmatic. We describe the epidemiology of
      MSSA colonization and infection in a 30-bed neonatal ward. DESIGN: Multimodal
      outbreak investigation SETTING: A public 800-bed tertiary care university
      hospital in Switzerland METHODS: Investigations in 2012-2013, triggered by a MSSA
      infection cluster, included prospective MSSA infection surveillance,
      microbiologic screening of neonates and environment, onsite observations, and a
      prospective cohort study. MSSA isolates were characterized by pulsed-field gel
      electrophoresis (PFGE) and selected isolates were examined for multilocus
      sequence type (MLST) and virulence factors. RESULTS: Among 726 in 2012, 30 (4.1%)
      patients suffered from MSSA infections including 8 (1.1%) with bacteremia. Among
      655 admissions in 2013, 13 (2.0%) suffered from MSSA infections including 2
      (0.3%) with bacteremia. Among 177 neonates screened for S. aureus carriage,
      overall 77 (44%) tested positive. A predominant PFGE-1-ST30 strain was identified
      in 6 of 30 infected neonates (20%) and 30 of 77 colonized neonates (39%). This
      persistent clone was pvl-negative, tst-positive and belonged to agr group III. We
      found no environmental point source. MSSA carriage was associated with central
      vascular catheter use but not with a particular midwife, nurse, physician, or
      isolette. Observed healthcare worker behavior may have propagated transmission
      via hands and fomites. Despite multimodal interventions, clonal transmission and
      colonization continued and another clone, PFGE-6-ST5, became predominant.
      CONCLUSIONS: Hospital-acquired MSSA clones represent a high proportion of MSSA
      colonization but not MSSA infections in neonate inpatients. In contrast to
      persisting MSSA, transmission infection rates decreased concurrently with
      interventions. It remains to be established whether eradication of hospital
      acquired MSSA strains would reduce infection rates further.

PMID- 26290399
TI  - A review of the clinical experience in pulsed dose rate brachytherapy.
AB  - Pulsed dose rate (PDR) brachytherapy is a treatment modality that combines
      physical advantages of high dose rate (HDR) brachytherapy with the
      radiobiological advantages of low dose rate brachytherapy. The aim of this review
      was to describe the effective clinical use of PDR brachytherapy worldwide in
      different tumour locations. We found 66 articles reporting on clinical PDR
      brachytherapy including the treatment procedure and outcome. Moreover, PDR
      brachytherapy has been applied in almost all tumour sites for which brachytherapy
      is indicated and with good local control and low toxicity. The main advantage of
      PDR is, because of the small pulse sizes used, the ability to spare normal
      tissue. In certain cases, HDR resembles PDR brachytherapy by the use of
      multifractionated low-fraction dose. 

PMID- 26290401
TI  - Phenolic Compounds from Atriplex littoralis and Their Radiation-Mitigating
      Activity.
AB  - From the aerial parts of Atriplex littoralis, three new flavonoid glycosides
      named atriplexins I-III (1-3), a known flavonoid glycoside, spinacetin 3-O-beta-d
      glucopyranoside (4), arbutin (5), and 4-hydroxybenzyl-beta-d-glucopyranoside (6)
      were isolated. Their structures were elucidated on the basis of detailed
      spectroscopic analysis, including 1D and 2D NMR (COSY, NOESY, TOCSY, HSQC, HMBC)
      and HRESITOF MS data. The compounds were tested for in vitro protective effects
      on chromosome aberrations in peripheral human lymphocytes using a cytochalasin-B
      blocked micronucleus (MN) assay in a concentration range of 0.8-7.4 MUM of final
      culture solution. Chromosomal damage was induced by 2 Gy of gamma-radiation on
      binucleated human lymphocytes, and the effects of the compounds were tested 2 to
      19 h after irradiation. The frequency of micronuclei (MNi) was scored in
      binucleated cells, and the nuclear proliferation index was calculated. The
      highest prevention of in vitro biochemical and cytogenetic damage of human
      lymphocytes induced by gamma-radiation was exhibited by 3 (reduction of MN
      frequency by 31%), followed by 4 and 6. 

PMID- 26290402
TI  - Participation of alkoxy groups in reactions of acetals: violation of the
      reactivity/selectivity principle in a Curtin-Hammett kinetic scenario.
AB  - Nucleophilic substitution reactions of acetals having benzyloxy groups four
      carbon atoms away can be highly diastereoselective. The selectivity in several
      cases increased as the reactivity of the nucleophile increased, in violation of
      the reactivity/selectivity principle. The increase in selectivity with reactivity
      suggests that multiple conformational isomers of reactive intermediates can give
      rise to the products. 

PMID- 26290403
TI  - Association between diabetes mellitus and oncological outcomes in bladder cancer
      patients undergoing radical cystectomy.
AB  - OBJECTIVE: To determine the association between diabetes mellitus and oncological
      outcomes in urothelial bladder cancer patients undergoing radical cystectomy.
      METHODS: From January 2004 to December 2014, 200 non-metastatic urothelial
      bladder cancer patients who underwent radical cystectomy were divided into two
      groups according to diabetes mellitus status at the time of surgery. Kaplan-Meier
      and Cox regression analysis were used to assess the association between diabetes
      mellitus and urothelial bladder cancer recurrence-free, cancer-specific and
      overall mortality. RESULTS: Of the 200 patients, 28 (14%) had diabetes mellitus
      and presented similar preoperative factors and pathological findings after
      radical cystectomy, including pathological stage, grade, lymph node invasion and
      positive surgical margin compared with non-diabetes mellitus patients (n = 172).
      The 5-year cancer-specific survivals were 92.3% and 62.1% in the non-diabetes
      mellitus and diabetes mellitus groups, respectively (P = 0.022). Multivariate Cox
      regression analysis showed that diabetes mellitus was a significant predictor for
      cancer-specific mortality (hazard ratio 1.785, P = 0.038). The 5-year overall
      survival rate was 92.1% and 59.4% in the non-diabetes mellitus and diabetes
      mellitus groups, respectively (P = 0.014), and diabetes mellitus was a
      significant factor for overall mortality by multivariate Cox regression analysis
      (hazard ratio 1.281, P = 0.042). CONCLUSIONS: Among bladder cancer patients who
      underwent radical cystectomy, the diabetes mellitus patients had worse cancer
      specific mortality and overall mortality outcomes than the non-diabetes mellitus
      patients. The mechanism of association between diabetes mellitus and urothelial
      bladder cancer should be investigated to validate the present results in a future
      prospective study.

PMID- 26290404
TI  - Global Proteomic Profiling of the Secretome of Candida albicans ecm33 Cell Wall
      Mutant Reveals the Involvement of Ecm33 in Sap2 Secretion.
AB  - Candida albicans secretes numerous proteins related to cell wall remodeling,
      adhesion, nutrient acquisition and host interactions. Also, extracellular
      vesicles containing cytoplasmic proteins are secreted into the medium. The C.
      albicans ecm33/ecm33 mutant (RML2U) presents an altered cell wall and is
      avirulent. The proteomic analysis of proteins secreted by RML2U cells identified
      a total of 170 proteins: 114 and 154 of which correspond to the vesicle-free
      secretome and extracellular vesicles, respectively. Notably, 98 proteins were
      common to both samples, and the groups most represented were metabolic and cell
      wall-related proteins. The results of this study showed that RML2U had an altered
      pattern of proteins secreted by the classical secretion pathway as well as the
      formation of extracellular vesicles, including their size, quantity, and protein
      composition. Specifically, the secretion of aspartic protease 2 (Sap2) was
      compromised but not its intracellular expression, with bovine serum albumin (BSA)
      degradation by RML2U being altered when BSA was used as the sole nitrogen source.
      Furthermore, as recent research links the expression of Sap2 to the TOR (Target
      Of Rapamycin) signaling pathway, the sensitivity of RML2U to rapamycin (the
      inhibitor of TOR kinase) was tested and found to be enhanced, connecting Ecm33
      with this pathway. 

PMID- 26290405
TI  - Effect of buffer conditions on CYP2C8-mediated paclitaxel 6alpha-hydroxylation
      and CYP3A4-mediated triazolam alpha- and 4-hydroxylation by human liver
      microsomes.
AB  - 1. Buffer conditions in in vitro metabolism studies using human liver microsomes
      (HLM) have been reported to affect the metabolic activities of several cytochrome
      P450 (CYP) isozymes in different ways, although there are no reports about the
      dependence of CYP2C8 activity on buffer conditions. 2. The present study
      investigated the effect of buffer components (phosphate or Tris-HCl) and their
      concentration (10-200 mM) on the CYP2C8 and CYP3A4 activities of HLM, using
      paclitaxel and triazolam, respectively, as marker substrates. 3. The Km (or S50)
      and Vmax values for both paclitaxel 6alpha-hydroxylation and triazolam alpha- and
      4-hydroxylation, estimated by fitting analyses based on the Michaelis-Menten or
      Hill equation, greatly depended on the buffer components and their concentration.
      4. The CLint values in phosphate buffer were 1.2-3.0-fold (paclitaxel) or 3.1-6.4
      fold (triazolam) higher than in Tris-HCl buffer at 50-100 mM. These values also
      depended on the buffer concentration, with a maximum 2.3-fold difference observed
      between 50 and 100 mM which are both commonly used in drug metabolism studies. 5.
      These findings suggest the necessity for optimization of the buffer conditions in
      the quantitative evaluation of metabolic clearances, such as in vitro-in vivo
      extrapolation and also estimating the contribution of a particular enzyme in drug
      metabolism.

PMID- 26290406
TI  - Lipid peroxidation evaluated in epidermis exfoliated during microdermabrasion is
      a reliable marker of oxidative stress related to obesity.

PMID- 26290407
TI  - Erratum to: Distribution of dipeptide repeat proteins in cellular models and
      C9orf72 mutation cases suggests link to transcriptional silencing.
AB  - As a result of an error during digital processing of Figure 1a for publication,
      one of the immunofluorescence panels (GA175-GFP Nucleolin staining) was
      accidentally strongly altered in contrast and brightness. The corrected version
      of the figure is shown below. The authors apologize for any confusion caused by
      this error. In the published article, the collaborators from the two
      institutions, German Consortium for Frontotemporal Lobar Degeneration and
      Bavarian Brain Banking Alliance, were incorrectly listed in article note. These
      names have been relocated to the Appendix section in the article now.Figure 1a
      and the collaborators list have been amended in the published article.

PMID- 26290408
TI  - Economic evaluation of occupational health and safety programmes in health care.
AB  - BACKGROUND: Evidence-based resource allocation in the public health care sector
      requires reliable economic evaluations that are different from those needed in
      the commercial sector. AIMS: To describe a framework for conducting economic
      evaluations of occupational health and safety (OHS) programmes in health care
      developed with sector stakeholders. To define key resources and outcomes to be
      considered in economic evaluations of OHS programmes and to integrate these into
      a comprehensive framework. METHODS: Participatory action research supported by
      mixed qualitative and quantitative methods, including a multi-stakeholder working
      group, 25 key informant interviews, a 41-member Delphi panel and structured
      nominal group discussions. RESULTS: We found three resources had top priority:
      OHS staff time, training the workers and programme planning, promotion and
      evaluation. Similarly, five outcomes had top priority: number of injuries, safety
      climate, job satisfaction, quality of care and work days lost. The resulting
      framework was built around seven principles of good practice that stakeholders
      can use to assist them in conducting economic evaluations of OHS programmes.
      CONCLUSIONS: Use of a framework resulting from this participatory action research
      approach may increase the quality of economic evaluations of OHS programmes and
      facilitate programme comparisons for evidence-based resource allocation
      decisions. The principles may be applicable to other service sectors funded from
      general taxes and more broadly to economic evaluations of OHS programmes in
      general.

PMID- 26290409
TI  - T cell types that take your breath away.
AB  - A new T helper cell signature in asthma patients highlights the potential impact
      of a personalized approach to asthma care (Choy et al., this issue). 

PMID- 26290410
TI  - Working stiff: how obesity boosts cancer risk.
AB  - Obesity promotes breast cancer by enhancing the stiffness of breast adipose
      tissue through changes in the extracellular matrix (Seo et al., this issue). 

PMID- 26290411
TI  - TH2 and TH17 inflammatory pathways are reciprocally regulated in asthma.
AB  - Increasing evidence suggests that asthma is a heterogeneous disorder regulated by
      distinct molecular mechanisms. In a cross-sectional study of asthmatics of
      varying severity (n = 51), endobronchial tissue gene expression analysis revealed
      three major patient clusters: TH2-high, TH17-high, and TH2/17-low. TH2-high and
      TH17-high patterns were mutually exclusive in individual patient samples, and
      their gene signatures were inversely correlated and differentially regulated by
      interleukin-13 (IL-13) and IL-17A. To understand this dichotomous pattern of T
      helper 2 (TH2) and TH17 signatures, we investigated the potential of type 2
      cytokine suppression in promoting TH17 responses in a preclinical model of
      allergen-induced asthma. Neutralization of IL-4 and/or IL-13 resulted in
      increased TH17 cells and neutrophilic inflammation in the lung. However,
      neutralization of IL-13 and IL-17 protected mice from eosinophilia, mucus
      hyperplasia, and airway hyperreactivity and abolished the neutrophilic
      inflammation, suggesting that combination therapies targeting both pathways may
      maximize therapeutic efficacy across a patient population comprising both TH2 and
      TH17 endotypes.

PMID- 26290413
TI  - High-throughput pairing of T cell receptor alpha and beta sequences.
AB  - The T cell receptor (TCR) protein is a heterodimer composed of an alpha chain and
      a beta chain. TCR genes undergo somatic DNA rearrangements to generate the
      diversity of T cell binding specificities needed for effective immunity.
      Recently, high-throughput immunosequencing methods have been developed to profile
      the TCR alpha (TCRA) and TCR beta (TCRB) repertoires. However, these methods
      cannot determine which TCRA and TCRB chains combine to form a specific TCR, which
      is essential for many functional and therapeutic applications. We describe and
      validate a method called pairSEQ, which can leverage the diversity of TCR
      sequences to accurately pair hundreds of thousands of TCRA and TCRB sequences in
      a single experiment. Our TCR pairing method uses standard laboratory consumables
      and equipment without the need for single-cell technologies. We show that pairSEQ
      can be applied to T cells from both blood and solid tissues, such as tumors.

PMID- 26290412
TI  - Obesity-dependent changes in interstitial ECM mechanics promote breast
      tumorigenesis.
AB  - Obesity and extracellular matrix (ECM) density are considered independent risk
      and prognostic factors for breast cancer. Whether they are functionally linked is
      uncertain. We investigated the hypothesis that obesity enhances local
      myofibroblast content in mammary adipose tissue and that these stromal changes
      increase malignant potential by enhancing interstitial ECM stiffness. Indeed,
      mammary fat of both diet- and genetically induced mouse models of obesity were
      enriched for myofibroblasts and stiffness-promoting ECM components. These
      differences were related to varied adipose stromal cell (ASC) characteristics
      because ASCs isolated from obese mice contained more myofibroblasts and deposited
      denser and stiffer ECMs relative to ASCs from lean control mice. Accordingly,
      decellularized matrices from obese ASCs stimulated mechanosignaling and thereby
      the malignant potential of breast cancer cells. Finally, the clinical relevance
      and translational potential of our findings were supported by analysis of patient
      specimens and the observation that caloric restriction in a mouse model reduces
      myofibroblast content in mammary fat. Collectively, these findings suggest that
      obesity-induced interstitial fibrosis promotes breast tumorigenesis by altering
      mammary ECM mechanics with important potential implications for anticancer
      therapies.

PMID- 26290415
TI  - A study on quality components and sleep-promoting effects of GABA black tea.
AB  - The aims of this study were to analyze the changes in quality components of gamma
      (gamma)-aminobutyric acid (GABA) black tea during processing, and to investigate
      the effect of three dosages of GABA black tea on sleep improvement. The results
      showed that the GABA content was increased significantly up to 2.70 mg g(-1)
      after vacuum anaerobic and aerobic treatment. In addition, the content of GABA
      after drying reached 2.34 mg g(-1), which achieved the standard of GABA tea.
      During the entire processing of GABA black tea, the contents of tea polyphenols,
      caffeine and total catechins displayed a gradually descending trend, while the
      contents of free amino acids and GABA were firstly increased, and then reduced.
      The GABA black tea had significant effects on prolonging the sleeping time with
      sodium pentobarbital (P < 0.05) and significantly enhancing the sleeping rate
      induced by sodium pentobarbital at a sub-threshold dose (P < 0.05). But its
      effect on shortening the sleeping latency period induced by sodium barbital was
      not significant (P > 0.05). It had no effect on directly inducing sleep and the
      mouse body weight. The extract of GABA black tea improved the sleeping quality of
      mice to extend with an optimal effect being found in the high dose-treated mice. 

PMID- 26290414
TI  - A synthetic consensus anti-spike protein DNA vaccine induces protective immunity
      against Middle East respiratory syndrome coronavirus in nonhuman primates.
AB  - First identified in 2012, Middle East respiratory syndrome (MERS) is caused by an
      emerging human coronavirus, which is distinct from the severe acute respiratory
      syndrome coronavirus (SARS-CoV), and represents a novel member of the lineage C
      betacoronoviruses. Since its identification, MERS coronavirus (MERS-CoV) has been
      linked to more than 1372 infections manifesting with severe morbidity and, often,
      mortality (about 495 deaths) in the Arabian Peninsula, Europe, and, most
      recently, the United States. Human-to-human transmission has been documented,
      with nosocomial transmission appearing to be an important route of infection. The
      recent increase in cases of MERS in the Middle East coupled with the lack of
      approved antiviral therapies or vaccines to treat or prevent this infection are
      causes for concern. We report on the development of a synthetic DNA vaccine
      against MERS-CoV. An optimized DNA vaccine encoding the MERS spike protein
      induced potent cellular immunity and antigen-specific neutralizing antibodies in
      mice, macaques, and camels. Vaccinated rhesus macaques seroconverted rapidly and
      exhibited high levels of virus-neutralizing activity. Upon MERS viral challenge,
      all of the monkeys in the control-vaccinated group developed characteristic
      disease, including pneumonia. Vaccinated macaques were protected and failed to
      demonstrate any clinical or radiographic signs of pneumonia. These studies
      demonstrate that a consensus MERS spike protein synthetic DNA vaccine can induce
      protective responses against viral challenge, indicating that this strategy may
      have value as a possible vaccine modality against this emerging pathogen.

PMID- 26290416
TI  - Breast cancer screening in the era of density notification legislation: summary
      of 2014 Massachusetts experience and suggestion of an evidence-based management
      algorithm by multi-disciplinary expert panel.
AB  - Stemming from breast density notification legislation in Massachusetts effective
      2015, we sought to develop a collaborative evidence-based approach to density
      notification that could be used by practitioners across the state. Our goal was
      to develop an evidence-based consensus management algorithm to help patients and
      health care providers follow best practices to implement a coordinated, evidence
      based, cost-effective, sustainable practice and to standardize care in
      recommendations for supplemental screening. We formed the Massachusetts Breast
      Risk Education and Assessment Task Force (MA-BREAST) a multi-institutional, multi
      disciplinary panel of expert radiologists, surgeons, primary care physicians, and
      oncologists to develop a collaborative approach to density notification
      legislation. Using evidence-based data from the Institute for Clinical and
      Economic Review, the Cochrane review, National Comprehensive Cancer Network
      guidelines, American Cancer Society recommendations, and American College of
      Radiology appropriateness criteria, the group collaboratively developed an
      evidence-based best-practices algorithm. The expert consensus algorithm uses
      breast density as one element in the risk stratification to determine the need
      for supplemental screening. Women with dense breasts and otherwise low risk (<15%
      lifetime risk), do not routinely require supplemental screening per the expert
      consensus. Women of high risk (>20% lifetime) should consider supplemental
      screening MRI in addition to routine mammography regardless of breast density. We
      report the development of the multi-disciplinary collaborative approach to
      density notification. We propose a risk stratification algorithm to assess
      personal level of risk to determine the need for supplemental screening for an
      individual woman.

PMID- 26290417
TI  - A comparison of registration errors with imageless computer navigation during MIS
      total knee arthroplasty versus standard incision total knee arthroplasty: a
      cadaveric study.
AB  - Optimal component alignment in total knee arthroplasty has been associated with
      better functional outcome as well as improved implant longevity. The ability to
      align components optimally during minimally invasive (MIS) total knee replacement
      (TKR) has been a cause of concern. Computer navigation is a useful aid in
      achieving the desired alignment although it is limited by the error during the
      manual registration of landmarks. Our study aims to compare the registration
      process error between a standard and a MIS surgical approach. We hypothesized
      that performing the registration error via an MIS approach would increase the
      registration process error. Five fresh frozen lower limbs were routinely prepared
      and draped. The registration process was performed through an MIS approach. This
      was then extended to the standard approach and the registration was performed
      again. Two surgeons performed the registration process five times with each
      approach. Performing the registration process through the MIS approach was not
      associated with higher error compared to the standard approach in the alignment
      parameters of interest. This rejects our hypothesis. Image-free navigated MIS TKR
      does not appear to carry higher risk of component malalignment due to the
      registration process error. Navigation can be used during MIS TKR to improve
      alignment without reduced accuracy due to the approach. 

PMID- 26290418
TI  - Role of 100S ribosomes in bacterial decay period.
AB  - Ribosomal proteins S10 and S2 were each fused with GFP to track the fates of
      these proteins in the stationary growth phase and the following decay period in
      Escherichia coli. The fused proteins localized mainly in the cytoplasm, and their
      amounts were proportional to the colony-forming unit. S10-GFP strains that lacked
      genes responsible for regulating 100S ribosomes and S2-GFP strain that was unable
      to form 100S both showed shortened stationary phases. This result indicates that
      these strains exhibit earlier death in the absence of 100S formation (S2-GFP, S10
      GFP?rmf and S10-GFP?hpf) and breakdown (S10-GFP?yfiA). Therefore, in addition to
      the mere presence of 100S, the correct timing of 100S formation and breakdown is
      required to maintain viability. We propose a model in which 100S acts as a
      tentative repository of ribosomes that are protected from degradation and provide
      a source of amino acids in later growth period. 

PMID- 26290419
TI  - Nek2 activation of Kif24 ensures cilium disassembly during the cell cycle.
AB  - Many proteins are known to promote ciliogenesis, but mechanisms that promote
      primary cilia disassembly before mitosis are largely unknown. Here we identify a
      mechanism that favours cilium disassembly and maintains the disassembled state.
      We show that co-localization of the S/G2 phase kinase, Nek2 and Kif24 triggers
      Kif24 phosphorylation, inhibiting cilia formation. We show that Kif24, a
      microtubule depolymerizing kinesin, is phosphorylated by Nek2, which stimulates
      its activity and prevents the outgrowth of cilia in proliferating cells,
      independent of Aurora A and HDAC6. Our data also suggest that cilium assembly and
      disassembly are in dynamic equilibrium, but Nek2 and Kif24 can shift the balance
      toward disassembly. Further, Nek2 and Kif24 are overexpressed in breast cancer
      cells, and ablation of these proteins restores ciliation in these cells, thereby
      reducing proliferation. Thus, Kif24 is a physiological substrate of Nek2, which
      regulates cilia disassembly through a concerted mechanism involving Kif24
      mediated microtubule depolymerization. 

PMID- 26290420
TI  - Theoretical and experimental (15)N NMR study of enamine-imine tautomerism of 4
      trifluoromethyl[b]benzo-1,4-diazepine system.
AB  - The tautomeric structure of 4-trifluoromethyl[b]benzo-1,4-diazepine system in
      solution has been evaluated by means of the calculation of (15)N NMR chemical
      shifts of individual tautomers in comparison with the averaged experimental
      shifts to show that the enamine-imine equilibrium is entirely shifted toward the
      imine form. The adequacy of the theoretical level used for the computation of
      (15)N NMR chemical shifts in this case has been verified based on the benchmark
      calculations in the series of the push-pull and captodative enamines together
      with related azomethynes, which demonstrated a good to excellent agreement with
      experiment.

PMID- 26290422
TI  - Pseudarthrosis after lumbar spinal fusion: the role of 18F-fluoride PET/CT.
AB  - PURPOSE: Painful pseudarthrosis is one of the most important indications for
      (revision) surgery after spinal fusion procedures. If pseudarthrosis is the
      source of recurrent pain it may require revision surgery. It is therefore of
      great clinical importance to ascertain if it is the source of such pain. The
      correlation between findings on conventional imaging (plain radiography and CT)
      and clinical well-being has been shown to be moderate. The goal of this study was
      to determine the possible role of (18)F-fluoride PET in patients after lumbar
      spinal interbody fusion by investigating the relationship between PET/CT findings
      and clinical function and pain. METHODS: A cohort of 36 patients was
      retrospectively included in the study after (18)F-fluoride PET/CT for either
      persistent or recurrent low back pain (18 patients) or during routine
      postoperative investigation (18 patients) between 9 and 76 months and 11 and 14
      months after posterior lumbar interbody fusion, respectively. Sixty minutes after
      intravenous injection of 156 - 263 MBq (mean 199 MBq, median 196 MBq) (18)F
      fluoride, PET and CT images were acquired using an integrated PET/CT scanner,
      followed by a diagnostic CT scan. Two observers independently scored the images.
      The number of bony bridges between vertebrae was scored on the CT images to
      quantify interbody fusion (0, 1 or 2). Vertebral endplate and intervertebral disc
      space uptake were evaluated visually as well as semiquantitatively following
      (18)F-fluoride PET. Findings on PET and CT were correlated with clinical
      wellbeing as measured by validated questionnaires concerning general daily
      functioning (Oswestry Disability Index), pain (visual analogue scale) and general
      health status (EuroQol). Patients were divided into three categories based on
      these questionnaire scores. RESULTS: No correlation was found between symptom
      severity and fusion status. However, (18)F-fluoride activity in the vertebral
      endplates was significantly higher in patients in the lowest Oswestry Disability
      Index category (i.e. with the worst clinical performance) than in patients in
      higher categories (p = 0.01 between categories 1 and 2 and 1 and 3). The visual
      analogue scale and EuroQol results were similar although less pronounced, with
      only SUVmax between category 1 and 2 being significantly different (p = 0.04).
      CONCLUSION: We hypothesize that (18)F-fluoride PET/CT may be able to provide
      support for the diagnosis of painful pseudarthrosis and could serve as a tool to
      discriminate between symptomatic and asymptomatic pseudarthrosis for revision
      surgery, as CT defines the consolidation status and PET pinpoints the 'stress
      reaction' at the vertebral endplates which significantly correlates with Oswestry
      Disability Index score.

PMID- 26290421
TI  - EANM procedural guidelines for radionuclide myocardial perfusion imaging with
      SPECT and SPECT/CT: 2015 revision.
AB  - Since the publication of the European Association of Nuclear Medicine (EANM)
      procedural guidelines for radionuclide myocardial perfusion imaging (MPI) in
      2005, many small and some larger steps of progress have been made, improving MPI
      procedures. In this paper, the major changes from the updated 2015 procedural
      guidelines are highlighted, focusing on the important changes related to new
      instrumentation with improved image information and the possibility to reduce
      radiation exposure, which is further discussed in relation to the recent
      developments of new International Commission on Radiological Protection (ICRP)
      models. Introduction of the selective coronary vasodilator regadenoson and the
      use of coronary CT-contrast agents for hybrid imaging with SPECT/CT angiography
      are other important areas for nuclear cardiology that were not included in the
      previous guidelines. A large number of minor changes have been described in more
      detail in the fully revised version available at the EANM home page:
      http://eanm.org/publications/guidelines/2015_07_EANM_FINAL_myocardial_perfusion_g
      ideline.pdf . 

PMID- 26290423
TI  - Characterization of age/sex and the regional distribution of mGluR5 availability
      in the healthy human brain measured by high-resolution [(11)C]ABP688 PET.
AB  - PURPOSE: Metabotropic glutamate receptor type 5 (mGluR5) is a G protein-coupled
      receptor that has been implicated in several psychiatric and neurological
      diseases. The radiopharmaceutical [(11)C]ABP688 allows for in vivo quantification
      of mGluR5 availability using positron emission tomography (PET). In this study,
      we aimed to detail the regional distribution of [(11)C]ABP688 binding potential
      (BPND) and the existence of age/sex effects in healthy individuals. METHODS:
      Thirty-one healthy individuals aged 20 to 77 years (men, n = 18, 45.3 +/- 18.2
      years; females, n = 13, 41.5 +/- 19.6 years) underwent imaging with [(11)C]ABP688
      using the high-resolution research tomograph (HRRT). We developed an advanced
      partial volume correction (PVC) method using surface-based analysis in order to
      accurately estimate the regional variation of radioactivity. BPND was calculated
      using the simplified reference tissue model, with the cerebellum as the reference
      region. Surface-based and volume-based analyses were performed for 39 cortical
      and subcortical regions of interest per hemisphere. RESULTS: We found the highest
      [(11)C]ABP688 BPND in the lateral prefrontal and anterior cingulate cortices. The
      lowest [(11)C]ABP688 BPND was observed in the pre- and post-central gyri as well
      as the occipital lobes and the thalami. No sex effect was observed. Associations
      between age and [(11)C]ABP688 BPND without PVC were observed in the right
      amygdala and left putamen, but were not significant after multiple comparisons
      correction. CONCLUSIONS: The present results highlight complexities underlying
      brain adaptations during the aging process, and support the notion that certain
      aspects of neurotransmission remain stable during the adult life span.

PMID- 26290424
TI  - Sympathetic nerve damage and restoration after ischemia-reperfusion injury as
      assessed by (11)C-hydroxyephedrine.
AB  - PURPOSE: An altered state of the cardiac sympathetic nerves is an important
      prognostic factor in patients with coronary artery disease. The aim of this study
      was to investigate regional sympathetic nerve damage and restoration utilizing a
      rat model of myocardial transient ischemia and a catecholamine analog PET tracer,
      (11)C-hydroxyephedrine ((11)C-HED). METHODS: Transient myocardial ischemia was
      induced by coronary occlusion for 20 min and reperfusion in male Wistar rats.
      Dual-tracer autoradiography was performed subacutely (7 days) and chronically (2
      months) after ischemia, and in control rats without ischemia using (11)C-HED as a
      marker of sympathetic innervation and (201)TI for perfusion. Additional serial in
      vivo cardiac (11)C-HED and (18)F-FDG PET scans were performed in the subacute and
      chronic phases after ischemia. RESULTS: After transient ischemia, the (11)C-HED
      uptake defect areas in both the subacute and chronic phases were clearly larger
      than the perfusion defect areas in the midventricular wall. The subacute (11)C
      HED uptake defect showed a transmural pattern, whereas uptake recovered in the
      subepicardial portion in the chronic phase. Tyrosine hydroxylase antibody nerve
      staining confirmed regional denervation corresponding to areas of decreased (11)C
      HED uptake. Serial in vivo PET imaging visualized reductions in the area of the
      (11)C-HED uptake defects in the chronic phase consistent with autoradiography and
      histology. CONCLUSION: Higher susceptibility of sympathetic neurons compared to
      myocytes was confirmed by a larger (11)C-HED defect with a corresponding
      histologically identified region of denervation. Furthermore, partial
      reinnervation was observed in the chronic phase as shown by recovery of
      subepicardial (11)C-HED uptake.

PMID- 26290425
TI  - Nucleostemin- and Oct 3/4-positive stem/progenitor cells exhibit disparate
      anatomical and temporal expression during rat Achilles tendon healing.
AB  - BACKGROUND: The recent discovery of residing tendon stem/progenitor cells has
      triggered a growing interest in stem cells as a useful tool in tendon repair. Our
      knowledge of their involvement in naturally healing tendons is, however, sparse.
      The aim of this study was to identify and determine stem/progenitor cells in
      relation to different healing phases and regions in a rat model of Achilles
      tendon rupture. METHODS: Surgery was performed to create a mid-tendon rupture on
      the right Achilles tendon of 24 rats, whereas the left tendon was used as a
      control. Tendons were harvested at one, two, eight and 17 weeks post-rupture and
      stained with antibodies specific to stem/progenitor cells (Octamer-binding
      transcription factor 3/4 (Oct 3/4) and nucleostemin), migrating cells (Dynamin 2
      (Dyn 2)) and leukocytes (CD45). A histological examination was performed on
      sections stained with Alcian blue. RESULTS: At one and two weeks post-rupture, a
      large number of stem/progenitor cells were discovered throughout the tendon. Most
      of these cells were nucleostemin positive, whereas only a few Oct 3/4-positive
      cells were found, mainly situated inside the injury region (I region). At eight
      and 17 weeks, the increment in stem/progenitor cells had diminished to equal that
      in the control tendons. At all time points, Oct 3/4-positive cells were also
      found in the connective tissue surrounding the tendon and at the muscle-tendon
      junction in both ruptured and control tendons and were often seen at the same
      location as the migration marker, Dyn 2. CONCLUSIONS: The whole length of the
      Achilles tendon is infiltrated by stem/progenitor cells at early time points
      after a mid-tendon rupture. However, different stem/progenitor cell populations
      exhibit varying anatomical and temporal expressions during Achilles tendon
      healing, suggesting distinct reparative implications. Oct 3/4 may thus act as a
      more local, migrating stem/progenitor cell involved in injury-site-specific
      regenerative effects, as compared to the more general proliferative role of
      nucleostemin-positive stem/progenitor cells.

PMID- 26290426
TI  - Increased prevalence of influenza B/Victoria lineage viruses during early stages
      of the 2015 influenza season in New South Wales, Australia: implications for
      vaccination and planning.
AB  - During the early weeks of the 2015 Australian influenza season, influenza B
      accounted for 67% (821/1,234) of all positive influenza tests in New South Wales.
      Of 81 successive influenza B viruses characterised, 33 (41%) were from children
      aged < 16 years; 23/81 (28%) belonged to the B/Victoria lineage. This lineage is
      not contained in the southern hemisphere's 2015 trivalent influenza vaccine. The
      significant B/Victoria lineage activity in the southern hemisphere suggests that
      the quadrivalent vaccine should be considered for the northern hemisphere.

PMID- 26290427
TI  - Ross River virus disease in two Dutch travellers returning from Australia,
      February to April 2015.
AB  - We report two cases of Ross River virus (RRV) infection in Dutch travellers who
      visited Australia during February to April 2015. These cases coincided with the
      largest recorded outbreak of RRV disease in Australia since 1996. This report
      serves to create awareness among physicians to consider travel-related RRV
      disease in differential diagnosis of patients with fever, arthralgia and/or rash
      returning from the South Pacific area, and to promote awareness among
      professionals advising travellers to this region.

PMID- 26290428
TI  - Detection of influenza A(H3N2) virus in children with suspected mumps during
      winter 2014/15 in England.
AB  - Influenza A(H3N2) virus was detected in oral fluid from 16/107 children (aged 2
      to 12 years) with a clinical diagnosis of mumps, who were sampled between
      December 2014 and February 2015 in England, during the peak of the 2014/15
      influenza season. Sequence analysis of an A(H3N2) virus from a child with
      suspected mumps showed the virus was similar to other circulating A(H3N2) viruses
      detected in winter 2014/15, which were antigenically drifted from the A(H3N2)
      vaccine strain.

PMID- 26290429
TI  - Risk factors for sporadic listeriosis in the Netherlands, 2008 to 2013.
AB  - Although the disease burden of listeriosis on population level is low, on
      individual level the impact is high, largely due to severe illness and a high
      case fatality. Identification of risk factors supports and specifies public
      health actions needed for prevention. We performed a case-control study to
      determine host- and food-related risk factors for non-perinatal listeriosis in
      the Netherlands. Patients with non-perinatal listeriosis reported between July
      2008 and December 2013 were compared with controls from a periodic control survey
      who completed a questionnaire in the same period. Higher age, male sex,
      underlying disease, especially cancer and kidney disease, and use of
      immunosuppressive medicine were strong risk factors for acquiring non-perinatal
      listeriosis. Analysis of the food consumption in the group of cases and controls
      with underlying diseases did not reveal any high-risk food products. Information
      and advice should continue to be given to persons at risk of severe listeriosis.
      Univariate analyses indicate that patients using gastric acid inhibitors are at
      risk. It is worth adding these patients to the group of susceptible persons.

PMID- 26290433
TI  - Admitting when mistakes are made.

PMID- 26290432
TI  - Gender-specific associations between ADIPOQ gene polymorphisms and adiponectin
      levels and obesity in the Jackson Heart Study cohort.
AB  - BACKGROUND: Despite the important role of adiponectin in regulating general
      metabolic homeostasis, analysis of genetic determinants of adiponectin and the
      related cardio-metabolic traits in African American population has been limited
      and inconsistent. Considering the high genetic admixture of African Americans and
      thus the important population stratification that may confound the genetic-trait
      associations, the objective of this work was to perform a comprehensive analysis
      of the associations between ADIPOQ variants and adiponectin levels and obesity
      phenotypes in a large African American population from the Jackson Heart Study
      (JHS) cohort. METHODS: Genotype data was available for 2968 JHS participants
      (1131men; 1837women). Single Nucleotide Polymorphisms (SNPs) were selected by a
      Tag-SNP Approach and literature review. The genotype imputation was performed
      using IMPUTE2 software and reference phased data from the 1000G project. PLINK
      software was used for the genetic analysis. Plasma specimens were analyzed by
      ELISA for adiponectin levels. All analyses were controlled for population
      stratification assessed by Individual Proportions of European Ancestry (PEA)
      estimates calculated in HAPMIX using ancestry informative markers (AIMs).
      RESULTS: We found a gender-dependent association of some ADIPOQ variants and
      adiponectin levels. In women four of the studied polymorphisms (rs6444174,
      rs16861205, rs1403697, rs7641507) were associated with adiponectin levels after
      Bonferroni correction and controlling for the percentage of PEA, age, annual
      household income and smoking. These results were consistent with the haplotype
      analysis. The association between the rs12495941 variant and obesity is modulated
      by the PEA, so that the relationship between the G allele and a higher incidence
      of obesity was present in those individuals within the lower PEA group. In
      addition we found an effect modification of obesity on the association between
      the ADIPOQ rs6444174 SNP and BMI so that the presence of the T allele was
      negatively and significantly associated with BMI only in participants with a
      normal weight. CONCLUSIONS: In this large African American cohort, ADIPOQ
      variants were associated with adiponectin levels in a gender-dependent manner and
      the relationship of some of these variants with obesity and BMI was modulated by
      the PEA and obesity status respectively. This suggests that the effects of these
      polymorphisms on adiponectin and obesity phenotypes are subject to a strong
      interaction with genetic and environmental factors in African American
      population.

PMID- 26290434
TI  - Quantitative analysis of recombination between YFP and CFP genes of FRET
      biosensors introduced by lentiviral or retroviral gene transfer.
AB  - Biosensors based on the principle of Forster (or fluorescence) resonance energy
      transfer (FRET) have been developed to visualize spatio-temporal dynamics of
      signalling molecules in living cells. Many of them adopt a backbone of
      intramolecular FRET biosensor with a cyan fluorescent protein (CFP) and yellow
      fluorescent protein (YFP) as donor and acceptor, respectively. However, there
      remains the difficulty of establishing cells stably expressing FRET biosensors
      with a YFP and CFP pair by lentiviral or retroviral gene transfer, due to the
      high incidence of recombination between YFP and CFP genes. To address this, we
      examined the effects of codon-diversification of YFP on the recombination of FRET
      biosensors introduced by lentivirus or retrovirus. The YFP gene that was fully
      codon-optimized to E.coli evaded the recombination in lentiviral or retroviral
      gene transfer, but the partially codon-diversified YFP did not. Further, the
      length of spacer between YFP and CFP genes clearly affected recombination
      efficiency, suggesting that the intramolecular template switching occurred in the
      reverse-transcription process. The simple mathematical model reproduced the
      experimental data sufficiently, yielding a recombination rate of 0.002-0.005 per
      base. Together, these results show that the codon-diversified YFP is a useful
      tool for expressing FRET biosensors by lentiviral or retroviral gene transfer. 

PMID- 26290436
TI  - Can she make it? Transportation barriers to accessing maternal and child health
      care services in rural Ghana.
AB  - BACKGROUND: The Ghana Community based Health Planning and Services (CHPS)
      strategy targets to bring health services to the doorsteps of clients in a manner
      that improves maternal and child health outcomes. In this strategy, referral is
      an important component but it is threatened in a rural context where
      transportation service is a problem. Few studies have examined perceptions of
      rural dwellers on transportation challenges in accessing maternal health care
      services within CHPS. METHODS: Using the political ecology of health framework,
      this paper investigates transportation barriers in health access in a rural
      context based on perceived cause, coping mechanisms and strategies for a
      sustainable transportation system. Eight (8) focus group discussions involving
      males (n = 40) and females (n = 45) in rural communities in a CHPS zone in the
      Upper West Region of Ghana were conducted between September and December 2013.
      RESULTS: Lack of vehicular transport is suppressing the potential positive impact
      of CHPS on maternal and child health. Consistent neglect of road infrastructural
      development and endemic poverty in the study area makes provision of alternative
      transport services for health care difficult. As a result, pregnant women use
      risky methods such as bicycle/tricycle/motorbikes to access obstetric health care
      services, and some turn to traditional medicines and traditional birth attendants
      for maternal health care services. CONCLUSION: These findings underscore the need
      for policy to address rural transport problems in order to improve maternal
      health. Community based transport strategy with CHPS is proposed to improve
      adherence to referral and access to emergency obstetric services.

PMID- 26290435
TI  - Treatment of systemic lupus erythematosus patients with the BAFF antagonist
      "peptibody" blisibimod (AMG 623/A-623): results from randomized, double-blind
      phase 1a and phase 1b trials.
AB  - INTRODUCTION: Blisibimod is a potent B cell-activating factor (BAFF) antagonist
      that binds to both cell membrane-expressed and soluble BAFF. The goal of these
      first-in-human studies was to characterize the safety, tolerability, and
      pharmacokinetic and pharmacodynamic profiles of blisibimod in subjects with
      systemic lupus erythematosus (SLE). METHODS: SLE subjects with mild disease that
      was stable/inactive at baseline received either a single dose of blisibimod (0.1,
      0.3, 1, or 3 mg/kg subcutaneous [SC] or 1, 3, or 6 mg/kg intravenous [IV]) or
      placebo (phase 1a; N = 54), or four weekly doses of blisibimod (0.3, 1, or 3
      mg/kg SC or 6 mg/kg IV) or placebo (phase 1b; N = 63). Safety and tolerability
      measures were collected, and B cell subset measurements and pharmacokinetic
      analyses were performed. RESULTS: All subjects (93 % female; mean age 43.7 years)
      carried the diagnosis of SLE for >= 1 year. Single- and multiple-dose treatment
      with blisibimod produced a decrease in the number of naive B cells (24-76 %) and
      a transient relative increase in the memory B cell compartment, with the greatest
      effect on IgD(-)CD27+; there were no notable changes in T cells or natural killer
      cells. With time, memory B cells reverted to baseline, leading to a calculated 30
      % reduction in total B cells by approximately 160 days after the first dose. In
      both the single- and multiple-dosing SC cohorts, the pharmacokinetic profile
      indicated slow absorption, dose-proportional exposure from 0.3 through 3.0 mg/kg
      SC and 1 through 6 mg/kg IV, linear pharmacokinetics across the dose range of 1.0
      6.0 mg/kg, and accumulation ratios ranging from 2.21 to 2.76. The relative
      increase in memory B cells was not associated with safety signals, and the
      incidence of adverse events, anti-blisibimod antibodies, and clinical laboratory
      abnormalities were comparable between blisibimod- and placebo-treated subjects.
      CONCLUSIONS: Blisibimod changed the constituency of the B cell pool and single
      and multiple doses of blisibimod exhibited approximate dose-proportional
      pharmacokinetics across the dose range 1.0-6.0 mg/kg. The safety and tolerability
      profile of blisibimod in SLE was comparable with that of placebo. These findings
      support further studies of blisibimod in SLE and other B cell-mediated diseases.
      TRIAL REGISTRATION: Clinicaltrials.gov NCT02443506 . Registered 11 May 2015.
      NCT02411136 Registered 7 April 2015.

PMID- 26290437
TI  - Effects of health intervention program on cardiometabolic risk profiles from
      health evaluation center in Asian population: a longitudinal study and propensity
      analysis.
AB  - BACKGROUND: Health intervention program (HIP) based on diet and lifestyle
      modifications had been shown to improve cardiovascular risks. The effects of such
      program on a variety of cardiometabolic outcome measures conducted in a strict
      analysis remained relatively unexplored. MATERIALS AND METHODS: A total of 2,660
      participants (mean age: 43.3 +/- 10 years, 63.6% male) underwent annual health
      survey from our health evaluation department. We implemented health intervention
      program (HIP) in which diet and lifestyle modifications including smoking
      cessation and advised physical activities were introduced. We further studied the
      effects of HIP on several cardiometabolic outcome measures including Framingham,
      metabolic scores and renal function in terms of Egfr with a mean follow-up period
      of 38.5 months. Propensity score (PS) matching (HIP vs non-HIP group) was used to
      avoid effects of case selection bias. RESULTS: Totally 1,004 (502 subjects for
      each group) left after PS matching protocol (both HIP and non-HIP group). The HIP
      group showed significant decline of waist circumference (-1.46 +/- 0.61, p =
      0.016), post-prandial glucose (-6.77 +/- 2.06, p = 0.001), and total cholesterol
      level (-4.42 +/- 2.15, p = 0.04), with borderline increase in eGFR (1.72 +/-
      0.94, p = 0.068) after an average of 1.91 +/- 1.14 year follow up period.
      Exercise behavior significantly increased for those who received HIP when
      compared to the non-HIP group (44.6 vs 52.4 %, p = 0.014). PS matching and
      difference-in-difference (DID) analysis further confirmed the beneficial effects
      of ATP III reduction by HIP (-0.36 +/- 0.06, p < 0.05). CONCLUSION: We
      demonstrated in our study that several cardiometabolic profiles can be
      substantially improved after health intervention introduction at the health
      evaluation center, supporting the beneficial evidence of such health intervention
      programs implementation based on primary prevention view points.

PMID- 26290438
TI  - MiR-186 suppresses the growth and metastasis of bladder cancer by targeting
      NSBP1.
AB  - BACKGROUND: Increasing evidence has shown that microRNAs function as oncogenes or
      tumor suppressors in human malignancies, but the roles of miR-186 in human
      bladder cancer (BC) is still unclear. METHODS: First, quantitative real-time PCR
      (qRT-PCR) was performed to detect miR-186 expression in bladder cancer tissues
      and cell lines. Then, Bioinformatics analysis, combined with luciferase reporter
      assay demonstrated the target gene of miR-186. Finally, the roles of miR-186 in
      regulation of tumor proliferation and invasion were further investigated.
      RESULTS: Here, our study showed miR-186 was down-regulated in bladder cancer
      tissues and cell lines. Luciferase reporter assay showed that miR-186 targets
      NSBP1 3'-untranslated region (UTR) directly and suppresses NSBP1 (HMGN5)
      expression in human bladder cancer cells. NSBP1 siRNA- and miR-186-mediated NSBP1
      knock-down experiments revealed that miR-186 suppresses cell proliferation and
      invasion through suppression of NSBP1 expression. Expression analysis of a set of
      epithelial-mesenchymal transition (EMT) markers showed that NSBP1 involves miR
      186 suppressed EMT which reducing the expression of mesenchymal markers (vimentin
      and N-cadherin) and inducing the expression of epithelial marker (E-cadherin).
      CONCLUSIONS: Our data first time identified miR-186 as the upstream regulator of
      NSBP1 and also suggest miR-186-suppressed NSBP1 as a novel therapeutic approach
      for bladder cancer.

PMID- 26290439
TI  - Community treatment orders: exploring the paradox of personalisation under
      compulsion.
AB  - The introduction of supervised community treatment, delivered through community
      treatment orders (CTOs) in England and Wales, contrasts with the policy of
      personalisation, which aims to provide service users autonomy and choice over
      services. This article draws upon findings from a primarily qualitative study
      which included 72 semi-structured interviews (conducted between January and
      December 2012) with practitioners, service users and nearest relatives situated
      within a particular NHS Trust. The article also refers to a follow-on study in
      which 30 Approved Mental Health Practitioners were interviewed. The studies aimed
      to develop a better understanding of how compulsory powers are being used in the
      community, within a policy context that emphasises personalisation and person
      centred care in service delivery. Findings from the interview data (which were
      analysed thematically) suggest that service users were often inadequately
      informed about the CTO and their legal rights. Furthermore, they tended to be
      offered little, or no, opportunity to make choices and have involvement in the
      making of the CTO and setting of conditions. Retrospectively, however,
      restrictions were often felt beneficial to recovery, and service users reported
      greater involvement in decisions at review stage. Areas of good practice are
      identified through which person-centred care can be better incorporated into the
      making of CTOs.

PMID- 26290442
TI  - Identification of a Rare beta(0)-Thalassemia Mutation, Codon 54 (-T) (HBB:
      c.165delT) in an Iranian Family.
AB  - beta-Thalassemia (beta-thal) is the most widespread autosomal recessive disorder
      worldwide. The present study describes a very rare beta-globin gene mutation,
      codon 54 (-T) (HBB: c.165delT), in a family from northern Iran. Nucleotide
      sequencing of amplified DNA obtained from a 28-year-old man revealed a deletion (
      T) at codon 54 of the beta-globin gene that results in a nonsense sequence at
      codon 60 and inphase termination at codon 59. Moreover, the haplotype combination
      of six different restriction enzyme sites in the beta-globin cluster was
      determined for this mutation. To the best of our knowledge, this is the second
      article reporting the codon 54 mutation worldwide and the first report of this
      mutation in the Iranian population, emphasizing the high heterogeneity of this
      population. 

PMID- 26290443
TI  - Multiplicative effect of serum phosphorus levels and insulin resistance on
      hypertensive vascular stiffness.

PMID- 26290441
TI  - Male and female mice show significant differences in hepatic transcriptomic
      response to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
AB  - BACKGROUND: 2,3,7,8-tetrachlorodibenzo-p-dixion (TCDD) is the most potent of the
      dioxin congeners, capable of causing a wide range of toxic effects across
      numerous animal models. Previous studies have demonstrated that males and females
      of the same species can display divergent sensitivity phenotypes to TCDD
      toxicities. Although it is now clear that most TCDD-induced toxic outcomes are
      mediated by the aryl hydrocarbon receptor (AHR), the mechanism of differential
      responses to TCDD exposure between sexes remains largely unknown. To investigate
      the differential sensitivities in male and female mice, we profiled the hepatic
      transcriptomic responses 4 days following exposure to various amounts of TCDD
      (125, 250, 500 or 1000 MUg/kg) in adult male and female C57BL/6Kuo mice. RESULTS:
      Several key findings were revealed by our study. 1) Hepatic transcriptomes varied
      significantly between the sexes at all doses examined. 2) The liver transcriptome
      of males was more dysregulated by TCDD than that of females. 3) The alteration of
      "AHR-core" genes was consistent in magnitude, regardless of sex. 4) A subset of
      genes demonstrated sex-dependent TCDD-induced transcriptional changes, including
      Fmo3 and Nr1i3, which were significantly induced in livers of male mice only. In
      addition, a meta-analysis was performed to contrast transcriptomic profiles of
      various organisms and tissues following exposure to equitoxic doses of TCDD.
      Minimal overlap was observed in the differences between TCDD-sensitive or TCDD
      resistant models. CONCLUSIONS: Sex-dependent sensitivities to TCDD exposure are
      associated with a set of sex-specific TCDD-responsive genes. In addition, complex
      interactions between the aryl hydrocarbon and sex hormone receptors may affect
      the observable differences in sensitivity phenotypes between the sexes. Further
      work is necessary to better understand the roles of those genes altered by TCDD
      in a sex-dependent manner, and their association with changes to sex hormones and
      receptors.

PMID- 26290444
TI  - Tracking sensory system atrophy and outcome prediction in spinal cord injury.
AB  - OBJECTIVE: In patients with subacute spinal cord injury (SCI), the motor system
      undergoes progressive structural changes rostral to the lesion, which are
      associated with motor outcome. The extent to which the sensory system is affected
      and how this relates to sensory outcome are uncertain. METHODS: Changes in the
      sensory system were prospectively followed by applying a comprehensive magnetic
      resonance imaging (MRI) protocol to 14 patients with subacute traumatic SCI at
      baseline, 2 months, 6 months, and 12 months after injury, combined with a full
      neurological examination and comprehensive pain assessment. Eighteen controls
      underwent the same MRI protocol. T1-weighted volumes, myelin-sensitive
      magnetization transfer saturation (MT), and longitudinal relaxation rate (R1)
      mapping provided data on spinal cord and brain morphometry and microstructure.
      Regression analysis assessed the relationship between MRI readouts and sensory
      outcomes. RESULTS: At 12 months from baseline, sensory scores were unchanged and
      below-level neuropathic pain became prominent. Compared with controls, patients
      showed progressive degenerative changes in cervical cord and brain morphometry
      across the sensory system. At 12 months, MT and R1 were reduced in areas of
      structural decline. Sensory scores at 12 months correlated with rate of change in
      cord area and brain volume and decreased MT in the spinal cord at 12 months.
      INTERPRETATION: This study has demonstrated progressive atrophic and
      microstructural changes across the sensory system with a close relation to
      sensory outcome. Structural MRI protocols remote from the site of lesion provide
      new insights into neuronal degeneration underpinning sensory disturbance and have
      potential as responsive biomarkers of rehabilitation and treatment interventions.

PMID- 26290445
TI  - Rapid Histone-Catalyzed DNA Lesion Excision and Accompanying Protein Modification
      in Nucleosomes and Nucleosome Core Particles.
AB  - C5'-Hydrogen atoms are frequently abstracted during DNA oxidation. The oxidized
      abasic lesion 5'-(2-phosphoryl-1,4-dioxobutane) (DOB) is an electrophilic product
      of the C5'-radical. DOB is a potent irreversible inhibitor of DNA polymerase
      beta, and forms interstrand cross-links in free DNA. We examined the reactivity
      of DOB within nucleosomes and nucleosome core particles (NCPs), the monomeric
      component of chromatin. Depending upon the position at which DOB is generated
      within a NCP, it is excised from nucleosomal DNA at a rate 275-1500-fold faster
      than that in free DNA. The half-life of DOB (7.0-16.8 min) in NCPs is shorter
      than any other abasic lesion. DOB's lifetime in NCPs is also significantly
      shorter than the estimated lifetime of an abasic site within a cell, suggesting
      that the observed chemistry would occur intracellularly. Histones also catalyze
      DOB excision when the lesion is present in the DNA linker region of a nucleosome.
      Schiff-base formation between DOB and histone proteins is detected in nucleosomes
      and NCPs, resulting in pyrrolone formation at the lysine residues. The lysines
      modified by DOB are often post-translationally modified. Consequently, the
      histone modifications described herein could affect the regulation of gene
      expression and may provide a chemical basis for the cytotoxicity of the DNA
      damaging agents that produce this lesion. 

PMID- 26290447
TI  - Cortical Maps.
AB  - In this article, we review functional organization in sensory cortical regions
      how the cortex represents the world. We consider four interrelated aspects of
      cortical organization: (1) the set of receptive fields of individual cortical
      sensory neurons, (2) how lateral interaction between cortical neurons reflects
      the similarity of their receptive fields, (3) the spatial distribution of
      receptive-field properties across the horizontal extent of the cortical tissue,
      and (4) how the spatial distributions of different receptive-field properties
      interact with one another. We show how these data are generally well explained by
      the theory of input-driven self-organization, with a family of computational
      models of cortical maps offering a parsimonious account for a wide range of map
      related phenomena. We then discuss important challenges to this explanation, with
      respect to the maps present at birth, maps present under activity blockade, the
      limits of adult plasticity, and the lack of some maps in rodents. Because there
      is not at present another credible general theory for cortical map development,
      we conclude by proposing key experiments to help uncover other mechanisms that
      might also be operating during map development.

PMID- 26290448
TI  - "It Was Like I Had Found My Tribe": Influence of a Neuroscience Outreach Program
      on High Achievers.
AB  - Engaging young people with science is essential to ensuring a scientifically
      literate society. Furthermore, it is important to enable access to a variety of
      sciences during adolescence, when individuals are making decisions about their
      future educational and career paths. The Brain Bee Challenge (BBC) is a quiz
      based international neuroscience outreach program for high school students. We
      wished to determine what influence exposure to the scientific research
      environment had on the highest achievers' later choices in education, their
      career expectations, and their perspectives toward science. Semistructured
      interviews were carried out with seven of the past winners of the New Zealand
      National BBC finals. Analysis involved thematic coding to investigate the impact
      of BBC involvement and potential longer term consequences. Second-order coding
      found critical themes identified by participants. These themes highlight the
      value of research institution-led outreach activities that extend high achievers
      beyond the school curriculum. In addition to subject-specific influences, there
      were multiple benefits acknowledged at a personal or individual level, including
      socialization and identity development, further demonstrating the importance of
      such engagement activities.

PMID- 26290449
TI  - Resting-state functional connectivity in the baboon model of genetic generalized
      epilepsy.
AB  - OBJECTIVE: The baboon provides a natural model of genetic generalized epilepsy
      (GGE). This study compares the intrinsic connectivity networks of epileptic and
      healthy control baboons using resting-state functional magnetic resonance imaging
      (rs-fMRI) and data-driven functional connectivity mapping. METHODS: Twenty
      baboons, matched for gender, age, and weight, were classified into two groups (10
      epileptic [EPI], 10 control [CTL]) on the basis of scalp electroencephalography
      (EEG) findings. Each animal underwent one MRI session that acquired one 5-min
      resting state fMRI scan and one anatomic MRI scan-used for registration and
      spatial normalization. Using independent component analysis, we identified 14
      unique components/networks, which were then used to characterize each group's
      functional connectivity maps of each brain network. RESULTS: The epileptic group
      demonstrated network-specific differences in functional connectivity when
      compared to the control animals. The sensitivity and specificity of the two
      groups' functional connectivity maps differed significantly in the visual, motor,
      amygdala, insular, and default mode networks. Significant increases were found in
      the occipital gyri of the epileptic group's functional connectivity map for the
      default mode, cingulate, intraparietal, motor, visual, amygdala, and thalamic
      regions. SIGNIFICANCE: This is the first study using resting-state fMRI to
      demonstrate intrinsic functional connectivity differences between epileptic and
      control nonhuman primates. These results are consistent with seed-based GGE
      studies in humans; however, our use of a data-driven approach expands the scope
      of functional connectivity mapping to include brain regions/networks comprising
      the whole brain.

PMID- 26290451
TI  - Smoking habits of italian athletes undergoing anti-doping control.

PMID- 26290450
TI  - PHD1 regulates p53-mediated colorectal cancer chemoresistance.
AB  - Overcoming resistance to chemotherapy is a major challenge in colorectal cancer
      (CRC) treatment, especially since the underlying molecular mechanisms remain
      unclear. We show that silencing of the prolyl hydroxylase domain protein PHD1,
      but not PHD2 or PHD3, prevents p53 activation upon chemotherapy in different CRC
      cell lines, thereby inhibiting DNA repair and favoring cell death.
      Mechanistically, PHD1 activity reinforces p53 binding to p38alpha kinase in a
      hydroxylation-dependent manner. Following p53-p38alpha interaction and
      chemotherapeutic damage, p53 can be phosphorylated at serine 15 and thus
      activated. Active p53 allows nucleotide excision repair by interacting with the
      DNA helicase XPB, thereby protecting from chemotherapy-induced apoptosis. In
      accord with this observation, PHD1 knockdown greatly sensitizes CRC to 5-FU in
      mice. We propose that PHD1 is part of the resistance machinery in CRC, supporting
      rational drug design of PHD1-specific inhibitors and their use in combination
      with chemotherapy. 

PMID- 26290452
TI  - Promoting Best Practices for Managing Acute Low Back Pain in an Occupational
      Environment.
AB  - Providers treating low back pain must be confident and knowledgeable in evidence
      based practice (EBP) to provide the best outcomes. An online education course was
      created in an effort to increase knowledge and confidence in EBP and clinical
      practice guidelines specific to low back pain in an occupational setting. There
      were 80 participants who completed the pre-test and post-test. The results showed
      a statistically significant improvement in knowledge and confidence scores after
      completion of the course. An online education course was shown to be a cost
      effective, accessible tool to increase knowledge and confidence of EBP for
      different health care providers. 

PMID- 26290446
TI  - The Insula: A "Hub of Activity" in Migraine.
AB  - The insula, a "cortical hub" buried within the lateral sulcus, is involved in a
      number of processes including goal-directed cognition, conscious awareness,
      autonomic regulation, interoception, and somatosensation. While some of these
      processes are well known in the clinical presentation of migraine (i.e.,
      autonomic and somatosensory alterations), other more complex behaviors in
      migraine, such as conscious awareness and error detection, are less well
      described. Since the insula processes and relays afferent inputs from brain areas
      involved in these functions to areas involved in higher cortical function such as
      frontal, temporal, and parietal regions, it may be implicated as a brain region
      that translates the signals of altered internal milieu in migraine, along with
      other chronic pain conditions, through the insula into complex behaviors. Here we
      review how the insula function and structure is altered in migraine. As a brain
      region of a number of brain functions, it may serve as a model to study new
      potential clinical perspectives for migraine treatment.

PMID- 26290454
TI  - Needlestick Injuries Among Nurses and Risk for HIV.

PMID- 26290455
TI  - Response to "Needlestick Injuries Among Nurses and Risk for HIV".

PMID- 26290458
TI  - Should we be prescribing isotretinoin to patients with peanut allergies?

PMID- 26290457
TI  - Association of Factor V Secretion with Protein Kinase B Signaling in Platelets
      from Horses with Atypical Equine Thrombasthenia.
AB  - BACKGROUND: Two congenital bleeding diatheses have been identified in
      Thoroughbred horses: Glanzmann thrombasthenia (GT) and a second, novel diathesis
      associated with abnormal platelet function in response to collagen and thrombin
      stimulation. HYPOTHESIS/OBJECTIVES: Platelet dysfunction in horses with this
      second thrombasthenia results from a secretory defect. ANIMALS: Two affected and
      6 clinically normal horses. METHODS: Ex vivo study. Washed platelets were
      examined for (1) expression of the alphaIIb-beta3 integrin; (2) fibrinogen
      binding capacity in response to ADP and thrombin; (3) secretion of dense and
      alpha-granules; (4) activation of the mammalian target of rapamycin (mTOR)
      protein kinase B (AKT) signaling pathway; and (5) cellular distribution of
      phosphatidylinositol-4-phosphate-3-kinase, class 2B (PIK3C2B) and SH2 containing
      inositol-5'-phosphatase 1 (SHIP1). RESULTS: Platelets from affected horses
      expressed normal amounts of alphaIIb-beta3 integrin and bound fibrinogen normally
      in response to ADP, but bound 80% less fibrinogen in response to thrombin. alpha
      granules only released 50% as much Factor V as control platelets, but dense
      granules released their contents normally. Protein kinase B (AKT) phosphorylation
      was reduced after thrombin activation, but mTOR Complex 2 (mTORC2) and
      phosphoinositide-dependent kinase 1 (PDK1) signaling were normal. SH2-containing
      inositol-5'-phosphatase 1 (SHIP1) did not localize to the cytoskeleton of
      affected platelets and was decreased overall consistent with reduced AKT
      phosphorylation. CONCLUSIONS AND CLINICAL SIGNIFICANCE: Defects in fibrinogen
      binding, granule secretion, and signal transduction are unique to this
      thrombasthenia, which we designate as atypical equine thrombasthenia.

PMID- 26290459
TI  - Up-regulated TLR4 in cardiomyocytes exacerbates heart failure after long-term
      myocardial infarction.
AB  - It remains unclear whether and how cardiomyocytes contribute to the inflammation
      in chronic heart failure (CHF). We recently reviewed the capacity of
      cardiomyocytes to initiate inflammation, by means of expressing certain immune
      receptors such as toll-like receptors (TLRs) that respond to pathogen- and damage
      associated molecular patterns (PAMP and DAMP). Previous studies observed TLR4
      mediated inflammation within days of myocardial infarction (MI). This study
      examined TLR4 expression and function in cardiomyocytes of failing hearts after 4
      weeks of MI in rats. The increases of TLR4 mRNA and proteins, as well as
      inflammatory cytokine production, were observed in both the infarct and remote
      myocardium. Enhanced immunostaining for TLR4 was observed in cardiomyocytes but
      not infiltrating leucocytes. The injection of lentivirus shRNA against TLR4 into
      the infarcted heart decreased inflammatory cytokine production and improved heart
      function in vivo. Accordingly, in cardiomyocytes isolated from CHF hearts,
      increases of TLR4 mRNA and proteins were detected. More robust binding of TLR4
      with lipopolysaccharide (LPS), a PAMP ligand for TLR4, and heat shock protein 60
      (HSP60), a DAMP ligand for TLR4, was observed in CHF cardiomyocytes under a
      confocal microscope. The maximum binding capacity (Bmax ) of TLR4 was increased
      for LPS and HSP60, whereas the binding affinity (Kd) was not significantly
      changed. Furthermore, both LPS and HSP60 induced more robust production of
      inflammatory cytokines in CHF cardiomyocytes, which was reduced by TLR4-blocking
      antibodies. We conclude that the expression, ligand-binding capacity and pro
      inflammatory function of cardiomyocyte TLR4 are up-regulated after long-term MI,
      which promote inflammation and exacerbate heart failure.

PMID- 26290460
TI  - The histone deacetylase inhibitor butyrate improves metabolism and reduces muscle
      atrophy during aging.
AB  - Sarcopenia, the loss of skeletal muscle mass and function during aging, is a
      major contributor to disability and frailty in the elderly. Previous studies
      found a protective effect of reduced histone deacetylase activity in models of
      neurogenic muscle atrophy. Because loss of muscle mass during aging is associated
      with loss of motor neuron innervation, we investigated the potential for the
      histone deacetylase (HDAC) inhibitor butyrate to modulate age-related muscle
      loss. Consistent with previous studies, we found significant loss of hindlimb
      muscle mass in 26-month-old C57Bl/6 female mice fed a control diet. Butyrate
      treatment starting at 16 months of age wholly or partially protected against
      muscle atrophy in hindlimb muscles. Butyrate increased muscle fiber cross
      sectional area and prevented intramuscular fat accumulation in the old mice. In
      addition to the protective effect on muscle mass, butyrate reduced fat mass and
      improved glucose metabolism in 26-month-old mice as determined by a glucose
      tolerance test. Furthermore, butyrate increased markers of mitochondrial
      biogenesis in skeletal muscle and whole-body oxygen consumption without affecting
      activity. The increase in mass in butyrate-treated mice was not due to reduced
      ubiquitin-mediated proteasomal degradation. However, butyrate reduced markers of
      oxidative stress and apoptosis and altered antioxidant enzyme activity. Our data
      is the first to show a beneficial effect of butyrate on muscle mass during aging
      and suggests HDACs contribute to age-related muscle atrophy and may be effective
      targets for intervention in sarcopenia and age-related metabolic disease.

PMID- 26290461
TI  - PERCEPTIONS OF CLOSE AND GROUP RELATIONSHIPS MEDIATE THE RELATIONSHIP BETWEEN
      ANXIETY AND DEPRESSION OVER A DECADE LATER.
AB  - BACKGROUND: Previous research has demonstrated that anxiety reliably predicts
      later depression, but little has been uncovered about the mechanism underlying
      this connection. Interpersonal relationships appear to be a viable mechanism of
      the association as anxiety has been shown to predict later deficits in both close
      (e.g., "best friendships") and group relationships (e.g., classroom peer groups),
      and deficits in both close and group relationships have been linked to later
      depressive symptoms. The current study examined close and group relationships as
      potential mediators between anxiety and depression 12-14 years later. METHODS: In
      a nationally representative sample of adolescents (N = 6,504), anxiety was
      measured at baseline, perceptions of close relationships (i.e., feeling loved)
      and perceptions of group relationships (i.e., feeling part of a group) were
      measured 6 months later, and depression levels and diagnosis were measured 12-14
      years later. RESULTS: Using structural equation models, the results showed that
      adolescent perceptions of both close and group relationships significantly
      mediated the relationship between adolescent anxiety and adult levels of
      depression. Furthermore, perceptions of not being accepted/loved in close
      relationships significantly mediated the relationship between adolescent anxiety
      and clinical depression in adulthood. CONCLUSIONS: These results suggest that a
      perception of not being accepted in group relationships may be a mechanism by
      which heightened anxiety in adolescents leads to heightened nonclinical
      depression in adulthood. On the other hand, adolescent perceptions of not feeling
      loved or accepted in close relationships may be a mechanism by which heightened
      anxiety in adolescence leads to clinical depression--in adulthood.

PMID- 26290462
TI  - New insights into PDE4B inhibitor selectivity: CoMFA analyses and molecular
      docking studies.
AB  - PDE4 inhibitors have been largely studied because of their promising therapeutic
      effects concerning inflammation and neurodegenerative dysfunctions, such as
      depression, schizophrenia and Alzheimer's diseases. In this context, the PDE4B
      isoform proved to be particularly involved in the activation of inflammatory
      responses, while the PDE4D subfamily is more associated with neuropathologies.
      The clinical use of PDE4 inhibitors was restricted by the presence of prominent
      side effects probably due to their non-specific action across the different
      isoforms. Therefore, this work deals with the development of 3D-QSAR models,
      supported by molecular docking studies, to identify the key requirements
      underlying selective PDE4B or PDE4D inhibition. The results highlighted the
      ligand-based approach as a promising tool to guide the rational design of novel
      PDE4 inhibitors endowed with high affinity and selectivity profiles. The
      alignment of compound 1-85 and the model A statistical results are depicted. 

PMID- 26290463
TI  - Retrobulbar lymphoma associated with a ballistic foreign body in a cat.
AB  - A seven-year-old domestic shorthair cat, adopted 5 years previously with a
      corneal perforation of the left eye, was presented for investigation of a left
      orbital mass. Computed tomography revealed a metallic foreign body within a
      contrast-enhancing, heterogeneous orbital mass. Large cell lymphoma was diagnosed
      from a fine needle aspirate. The cat staged negatively and was treated with L
      asparaginase, prednisolone and three fractions of radiation therapy. A rapid
      clinical remission was obtained and the cat remained in remission for 3 years
      after therapy. This is the first report of large cell lymphoma likely occurring
      secondary to a foreign body.

PMID- 26290465
TI  - A novel protocol for the facile construction of tetrahydroquinoline fused
      tricyclic frameworks via an intramolecular 1,3-dipolar nitrile oxide
      cycloaddition reaction.
AB  - An efficient method towards the synthesis of quinoline fused tricyclic compounds
      involving an intramolecular 1,3-dipolar nitrile oxide cycloaddition reaction
      utilizing Baylis-Hillman derivatives in good yields has been described for the
      first time. A highly functionalized tricyclic framework was created by forming
      two rings and two adjacent stereocentres through the formation of two N-C bonds,
      one C-C bond and one O-C bond in a highly regio and diastereoselective manner. 

PMID- 26290464
TI  - Molecular Insight in the Multifunctional Effects of Oridonin.
AB  - Oridonin has attracted considerable attention in the last decade because of its
      anti-cancer pharmacological properties. This ent-kaurane diterpenoid, isolated
      from the Chinese herb Rabdosia rubescens and some related species, has
      demonstrated great potential in the treatment profile of many diseases by
      exerting anti-tumor, anti-inflammatory, pro-apoptotic, and neurological effects.
      Unfortunately, the mechanisms via which oridonin exerts these effects remain
      poorly understood. This review provides an overview of the multifunctional
      effects of oridonin as well as the reasons for its potential for investigations
      in the treatment of many diseases other than cancer. 

PMID- 26290466
TI  - The effects of somatostatin analogue therapy on pituitary tumor volume in
      patients with acromegaly.
AB  - INTRODUCTION: In nearly all cases, acromegaly is caused by excess GH from a
      pituitary adenoma, resulting in elevated circulating levels of GH and,
      subsequently, IGF-1. Treatment goals are to eliminate morbidity and restore the
      increased mortality to normal rates. Therapeutic strategies aim to minimize tumor
      mass and normalize GH and IGF-1 levels. Somatostatin analogues are the medical
      treatment of choice in acromegaly, as first-line or post-surgical therapy, and
      have proven efficacy in pituitary tumor volume reduction (TVR). METHODS: Here we
      review the effects of somatostatin analogue therapy on pituitary tumor volume in
      patients with acromegaly. RESULTS: TVR with somatostatin analogues may be
      mediated by direct anti-proliferative effects via activation of somatostatin
      receptors, or by indirect effects, such as angiogenesis inhibition, and is more
      pronounced when they are administered as first-line therapy. Various studies of
      first-line treatment with octreotide LAR have shown significant TVR in >=73% of
      patients. First-line treatment with lanreotide Autogel has shown evidence of TVR,
      although more studies are needed. In a recent randomized, double-blind, 12-month
      trial in 358 medical-treatment-naive acromegaly patients, significant TVR was
      achieved by 81% of patients administered pasireotide LAR and 77% administered
      octreotide LAR. Pre-operative somatostatin analogue therapy may also induce TVR
      and improve post-operative disease control compared with surgery alone. TVR is
      progressive with prolonged treatment, and decreased IGF-1 levels may be its best
      predictor, followed by age and degree of GH decrease. However, TVR does not
      always correlate with degree of biochemical control. CONCLUSION: Somatostatin
      analogues (first- or second-line treatment) are the mainstay of medical therapy
      and, as first-line medical therapy, are associated with significant pituitary TVR
      in most patients.

PMID- 26290468
TI  - A Novel Mutation in RPL10 (Ribosomal Protein L10) Causes X-Linked Intellectual
      Disability, Cerebellar Hypoplasia, and Spondylo-Epiphyseal Dysplasia.
AB  - RPL10 encodes ribosomal protein L10 (uL16), a highly conserved multifunctional
      component of the large ribosomal subunit, involved in ribosome biogenesis and
      function. Using X-exome resequencing, we identified a novel missense mutation
      (c.191C>T; p.(A64V)) in the N-terminal domain of the protein, in a family with
      two affected cousins presenting with X-linked intellectual disability, cerebellar
      hypoplasia, and spondylo-epiphyseal dysplasia (SED). We assessed the impact of
      the mutation on the translational capacity of the cell using yeast as model
      system. The mutation generates a functional ribosomal protein, able to complement
      the translational defects of a conditional lethal mutation of yeast rpl10.
      However, unlike previously reported mutations, this novel RPL10 missense mutation
      results in an increase in the actively translating ribosome population. Our
      results expand the mutational and clinical spectrum of RPL10 identifying a new
      genetic cause of SED and highlight the emerging role of ribosomal proteins in the
      pathogenesis of neurodevelopmental disorders. 

PMID- 26290469
TI  - Reciprocity in therapeutic relationships: A conceptual review.
AB  - Reciprocity has generally been understood as a process of giving and taking,
      within an exchange of emotions or services, and has long been recognized as a
      central part of human life. However, an understanding of reciprocity in
      professional helping relationships has seldom received attention, despite
      movements in mental health care towards more collaborative approaches between
      service users and professionals. In this review, a systematic search of the
      published papers was conducted in order to explore how reciprocity is
      conceptualized and understood as part of the dyadic therapeutic relationship
      between professionals and service users. Eleven papers met our inclusion criteria
      and a narrative synthesis was used to synthesize the key concepts of reciprocity.
      The concepts of: 'dynamic equilibrium', 'shared affect', 'asymmetric alliance',
      and 'recognition as a fellow human being' were recurrent in understandings of
      reciprocity in professional contexts. These conceptualizations of reciprocity
      were also linked to specific behavioural and psychological processes. The
      findings suggest that reciprocity may be conceptualized and incorporated as a
      component of mental health care, with recurrent and observable processes which
      may be harnessed to promote positive outcomes for service users. To this end, we
      make recommendations for further research to progress and develop reciprocal
      processes in mental health care. 

PMID- 26290467
TI  - Exome sequencing identified FGF12 as a novel candidate gene for Kashin-Beck
      disease.
AB  - The objective of this study was to identify novel causal genes involved in the
      pathogenesis of Kashin-Beck disease (KBD). A representative grade III KBD sib
      pair with serious skeletal growth and development failure was subjected to exome
      sequencing using the Illumina Hiseq2000 platform. The detected gene mutations
      were then filtered against the data of 1000 Genome Project, dbSNP database, and
      BGI inhouse database, and replicated by a genome-wide association study (GWAS) of
      KBD. Ninety grade II or III KBD patients with extreme KBD phenotypes and 1627
      healthy controls were enrolled in the GWAS. Affymetrix Genome-Wide Human SNP
      Array 6.0 was applied for genotyping. PLINK software was used for association
      analysis. We identified a novel 106T>C at the 3'UTR of the FGF12 gene, which has
      not been reported by now. Sequence alignment observed high conversation at the
      mutated 3'UTR+106T>C locus across various vertebrates. In the GWAS of KBD, we
      detected nine SNPs of the FGF12 gene showing association evidence (P value <
      0.05) with KBD. The most significant association signal was observed at rs1847340
      (P value = 1.90 * 10(-5)). This study suggests that FGF12 was a susceptibility
      gene of KBD. Our results provide novel clues for revealing the pathogenesis of
      KBD and the biological function of FGF12.

PMID- 26290471
TI  - Climate change: Assessing effects on health and wealth of populations.

PMID- 26290470
TI  - Austerity, precariousness, and the health status of Greek labour market
      participants: Retrospective cohort analysis of employed and unemployed persons in
      2008-2009 and 2010-2011.
AB  - Greece implemented the deepest austerity package in Europe during the Great
      Recession (from 2008), including reductions in severance pay and redundancy
      notice periods. To evaluate whether these measures worsened labour market
      participants' health status, we compared changes in self-reported health using
      two cohorts of employed individuals in Greece from the European Union Statistics
      on Income and Living Conditions. During the initial recession (2008-2009) we
      found that self-reported health worsened both for those remaining in employment
      and those who lost jobs. Similarly, during the austerity programme (2010-2011)
      people who lost jobs experienced greater health declines. Importantly,
      individuals who remained employed in 2011 were also 25 per cent more likely to
      experience a health decline than in 2009. These harms appeared concentrated in
      people aged 45-54 who lost jobs. Our study moves beyond existing findings by
      demonstrating that austerity both exacerbates the negative health consequences of
      job loss and worsens the health of those still employed. 

PMID- 26290472
TI  - Effect of ethnicity and socioeconomic variation to the gut microbiota composition
      among pre-adolescent in Malaysia.
AB  - Gut microbiota plays an important role in mammalian host metabolism and
      physiological functions. The functions are particularly important in young
      children where rapid mental and physical developments are taking place.
      Nevertheless, little is known about the gut microbiome and the factors that
      contribute to microbial variation in the gut of South East Asian children. Here,
      we compared the gut bacterial richness and composition of pre-adolescence in
      Northern Malaysia. Our subjects covered three distinct ethnic groups with
      relatively narrow range of socioeconomic discrepancy. These included the Malays
      (n = 24), Chinese (n = 17) and the Orang Asli (indigenous) (n = 20). Our results
      suggested a strong ethnicity and socioeconomic-linked bacterial diversity.
      Highest bacterial diversity was detected from the economically deprived
      indigenous children while the lowest diversity was recorded from the relatively
      wealthy Chinese children. In addition, predicted functional metagenome profiling
      suggested an over-representation of pathways pertinent to bacterial colonisation
      and chemotaxis in the former while the latter exhibited enriched gene pathways
      related to sugar metabolism. 

PMID- 26290474
TI  - Vitamin C promotes wound healing through novel pleiotropic mechanisms.
AB  - Vitamin C (VitC) or ascorbic acid (AscA), a cofactor for collagen synthesis and a
      primary antioxidant, is rapidly consumed post-wounding. Parenteral VitC
      administration suppresses pro-inflammatory responses while promoting anti
      inflammatory and pro-resolution effects in human/murine sepsis. We hypothesised
      that VitC could promote wound healing by altering the inflammatory, proliferative
      and remodelling phases of wound healing. Mice unable to synthesise VitC (Gulo(-/
      ) ) were used in this study. VitC was provided in the water (sufficient),
      withheld from another group (deficient) and supplemented by daily intra
      peritoneal infusion (200 mg/kg, deficient + AscA) in a third group. Full
      thickness excisional wounds (6 mm) were created and tissue collected on days 7
      and 14 for histology, quantitative polymerase chain reaction (qPCR) and Western
      blotting. Human neonatal dermal fibroblasts (HnDFs) were used to assess effects
      of In conclusion, VitC favorably on proliferation. Histological analysis showed
      improved wound matrix deposition and organisation in sufficient and deficient
      +AscA mice. Wounds from VitC sufficient and deficient + AscA mice had reduced
      expression of pro-inflammatory mediators and higher expression of wound healing
      mediators. Supplementation of HnDF with AscA induced the expression of self
      renewal genes and promoted fibroblast proliferation. VitC favourably impacts the
      spatiotemporal expression of transcripts associated with early resolution of
      inflammation and tissue remodelling. 

PMID- 26290473
TI  - Risk stratification in autoimmune cholestatic liver diseases: Opportunities for
      clinicians and trialists.
AB  - Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are
      infrequent autoimmune cholestatic liver diseases, that disproportionate to their
      incidence and prevalence, remain very important causes of morbidity and mortality
      for patients with liver disease. Mechanistic insights spanning genetic risks and
      biological pathways to liver injury and fibrosis have led to a renewed interest
      in developing therapies beyond ursodeoxycholic acid that are aimed at both
      slowing disease course and improving quality of life. International cohort
      studies have facilitated a much greater understanding of disease heterogeneity,
      and in so doing highlight the opportunity to provide patients with a more
      individualized assessment of their risk of progressive liver disease, based on
      clinical, laboratory, or imaging findings. This has led to a new approach to
      patient care that focuses on risk stratification (both high and low risk); and
      furthermore allows such stratification tools to help identify patient subgroups
      at greatest potential benefit from inclusion in clinical trials. In this article,
      we review the applicability and validity of risk stratification in autoimmune
      cholestatic liver disease, highlighting strengths and weaknesses of current and
      emergent approaches. (Hepatology 2016;63:644-659). 

PMID- 26290476
TI  - Socioeconomic position in young adulthood is associated with BMI in Australian
      families.
AB  - BACKGROUND: Low socioeconomic position (SEP) is associated with increased
      cardiovascular (CV) disease risk, but the relative importance of SEP in childhood
      and adulthood, and of changes in SEP between these two life stages, remains
      unclear. Studies of families may help clarify these issues. We aimed to assess
      whether SEP in young adulthood, or change in SEP from childhood to young
      adulthood, was associated with five continuously measured CV risk factors.
      METHODS: We used data from 286 adult Australian families from the Victorian
      Family Heart Study (VFHS), in which some offspring have left home (n = 364) and
      some remained at home (n = 199). SEP (defined as the Index of Relative
      Socioeconomic Disadvantage) was matched to addresses. We fitted variance
      components models to test whether young adult SEP and/or change in SEP was
      associated with systolic blood pressure, diastolic blood pressure, body mass
      index (BMI), total cholesterol or high-density lipoprotein cholesterol, after
      adjustment for parental SEP and within-family correlation. RESULTS: An increase
      in SEP of 100 SEIFA units from childhood to adulthood was associated with a lower
      BMI (beta = -0.49 kg/m(2), P < 0.01) only. CONCLUSIONS: These results suggest
      that a change in SEP in young adulthood is an important predictor of BMI,
      independent of childhood SEP.

PMID- 26290475
TI  - ZnuA and zinc homeostasis in Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is a ubiquitous environmental bacterium and a clinically
      significant opportunistic human pathogen. Central to the ability of P. aeruginosa
      to colonise both environmental and host niches is the acquisition of zinc. Here
      we show that P. aeruginosa PAO1 acquires zinc via an ATP-binding cassette (ABC)
      permease in which ZnuA is the high affinity, zinc-specific binding protein. Zinc
      uptake in Gram-negative organisms predominantly occurs via an ABC permease, and
      consistent with this expectation a P. aeruginosa DeltaznuA mutant strain showed
      an ~60% reduction in cellular zinc accumulation, while other metal ions were
      essentially unaffected. Despite the major reduction in zinc accumulation, minimal
      phenotypic differences were observed between the wild-type and DeltaznuA mutant
      strains. However, the effect of zinc limitation on the transcriptome of P.
      aeruginosa PAO1 revealed significant changes in gene expression that enable
      adaptation to low-zinc conditions. Genes significantly up-regulated included non
      zinc-requiring paralogs of zinc-dependent proteins and a number of novel import
      pathways associated with zinc acquisition. Collectively, this study provides new
      insight into the acquisition of zinc by P. aeruginosa PAO1, revealing a hitherto
      unrecognized complexity in zinc homeostasis that enables the bacterium to survive
      under zinc limitation. 

PMID- 26290477
TI  - An interactive method for engaging the public health workforce with evidence.

PMID- 26290478
TI  - Electroless Deposition of III-V Semiconductor Nanostructures from Ionic Liquids
      at Room Temperature.
AB  - Group III-V semiconductor nanostructures are important materials in
      optoelectronic devices and are being researched in energy-related fields. A
      simple approach for the synthesis of these semiconductors with well-defined
      nanostructures is desired. Electroless deposition (galvanic displacement) is a
      fast and versatile technique for deposition of one material on another and
      depends on the redox potentials of the two materials. Herein we show that GaSb
      can be directly synthesized at room temperature by galvanic displacement of SbCl3
      /ionic liquid on electrodeposited Ga, on Ga nanowires, and also on commercial Ga.
      In situ AFM revealed the galvanic displacement process of Sb on Ga and showed
      that the displacement process continues even after the formation of GaSb. The
      bandgap of the deposited GaSb was 0.9+/-0.1 eV compared to its usual bandgap of
      0.7 eV. By changing the cation in the ionic liquid, the redox process could be
      varied leading to GaSb with different optical properties.

PMID- 26290479
TI  - Neonatal drug withdrawal syndrome: cross-country comparison using hospital
      administrative data in England, the USA, Western Australia and Ontario, Canada.
AB  - OBJECTIVES: We determined trends over time in the prevalence of neonatal drug
      withdrawal syndrome (NWS) in England compared with that reported in the USA,
      Western (W) Australia and Ontario, Canada. We also examined variation in
      prevalence of NWS according to maternal age, birth weight and across the English
      NHS by hospital trusts. DESIGN AND SETTING: Retrospective study using national
      hospital administrative data (Hospital Episode Statistics) for the NHS in England
      between 1997 and 2011. NWS was identified using international classification of
      disease codes in hospital admission records. We searched the research literature
      and contacted researchers to identify studies reporting trends in the prevalence
      of NWS. MAIN OUTCOME MEASURES: Prevalence of NWS by calendar year per 1000 live
      births for each country/state. For births in England, prevalence by maternal age
      group and birth weight group. Prevalence by NHS trust and region at birth, and
      funnel plot to show outlying English NHS hospital trusts (>3 SD of mean
      prevalence). MAIN RESULTS: Mean prevalence rates of recorded NWS increased in all
      four countries. Rates stabilised in England and W. Australia from the early 2000s
      and rose steeply in the USA and Ontario during the late 2000s. The most recent
      prevalence rates were 2.7/1000 live births in England (2011; 1544 cases);
      2.7/1000 in W. Australia (2009); 3.6/1000 in the USA (2009) and 5.1/1000 in
      Ontario (2011). The highest prevalence in England was among babies born to
      mothers aged 25-34 years at delivery and among babies born with low birth weight
      (1500-2500 g). In England in 2011, 8.6% of hospital trusts had a recorded
      prevalence outside 3 SD of the overall average (7% above, 1% below). The North
      East region of England had the highest recorded prevalence of NWS. CONCLUSIONS:
      Although recorded NWS is stable in England and W. Australia, rising rates in the
      USA and Ontario may reflect better recognition and/or increased use of prescribed
      opiate analgesics and highlight the need for surveillance. The extent to which
      different prevalence rates by hospital trust reflect variation in occurrence,
      recognition or recording requires further investigation.

PMID- 26290480
TI  - Antenatal substance misuse and smoking and newborn hypoxic challenge response.
AB  - OBJECTIVES: Infants of smoking (S) and substance misusing (SM) mothers have an
      increased risk of sudden infant death syndrome. The aim of this study was to test
      the hypothesis that infants of SM or S mothers compared with infants of non-SM,
      non-smoking mothers (controls) would have a poorer ventilatory response to
      hypoxia, which was particularly marked in the SM infants. DESIGN: Physiological
      study. SETTING: Tertiary perinatal centre. PATIENTS: 21 SM; 21 S and 19 control
      infants. Infants were assessed before maternity/neonatal unit discharge.
      INTERVENTIONS: Maternal and infant urine samples were tested for cotinine,
      cannabinoids, opiates, amphetamines, methadone, cocaine and benzodiazepines. MAIN
      OUTCOME MEASURES: During quiet sleep, the infants were switched from breathing
      room air to 15% oxygen and changes in minute volume were assessed. RESULTS: The
      SM infants had a greater mean increase (p=0.028, p=0.034, respectively) and a
      greater magnitude of decline (p<0.001, p=0.018, respectively) in minute volume
      than the S infants and the controls. The rate of decline in minute volume was
      greater in the SM infants (p=0.008) and the S infants (p=0.011) compared with the
      controls. CONCLUSIONS: Antenatal substance misuse and smoking affect the infant's
      ventilatory response to a hypoxic challenge.

PMID- 26290481
TI  - Efficacy of clindamycin phosphate and benzoyl peroxide gel (DUAC((r)) ) in the
      treatment of EGFR inhibitors-associated acneiform eruption.

PMID- 26290482
TI  - The precision of value-based choices depends causally on fronto-parietal phase
      coupling.
AB  - Which meal would you like today, chicken or pasta? For such value-based choices,
      organisms must flexibly integrate various types of sensory information about
      internal states and the environment to transform them into actions. Recent
      accounts suggest that these choice-relevant processes are mediated by information
      transfer between functionally specialized but spatially distributed brain regions
      in parietal and prefrontal cortex; however, it remains unclear whether such
      fronto-parietal communication is causally involved in guiding value-based
      choices. We find that transcranially inducing oscillatory desynchronization
      between the frontopolar and -parietal cortex leads to more inaccurate choices
      between food rewards while leaving closely matched perceptual decisions
      unaffected. Computational modelling shows that this exogenous manipulation leads
      to imprecise value assignments to the choice alternatives. Thus, our study
      demonstrates that accurate value-based decisions critically involve coherent
      rhythmic information transfer between fronto-parietal brain areas and establishes
      an experimental approach to non-invasively manipulate the precision of value
      based choices in humans. 

PMID- 26290484
TI  - Attention, Motivation, and Study Habits in Users of Unprescribed ADHD Medication.
AB  - OBJECTIVE: Despite the limited effectiveness of ADHD medications on healthy
      cognition, prescription stimulants' cognitive enhancement use is increasing. This
      article examines enhancement users' attention, motivation, and study habits.
      METHOD: A total of 61 users of unprescribed stimulants and 67 controls (no
      history of prescription stimulant use) completed tests of objectively measured
      and subjectively reported attention. Self-reports on study habits, as well as
      motivation during laboratory attention testing, were also administered. RESULTS:
      Our data replicated previous findings of relatively lower self-reported attention
      functioning in users. Extending past research, we showed that user-control
      differences in attention were still present but less pronounced on objective
      measures than on self-report. In addition, we obtained evidence of lower
      motivation during cognitive testing and less optimal study habits among users, as
      compared with their non-using peers. CONCLUSION: Unprescribed stimulant use is
      more strongly related to compromised study habits, low motivation, and a
      subjective perception of attention problems than to objective attention
      performance.

PMID- 26290483
TI  - Is chlamydia screening and testing in Britain reaching young adults at risk of
      infection? Findings from the third National Survey of Sexual Attitudes and
      Lifestyles (Natsal-3).
AB  - BACKGROUND: In the context of widespread opportunistic chlamydia screening among
      young adults, we aimed to quantify chlamydia testing and diagnosis among 16-24
      year olds in Britain in relation to risk factors for prevalent chlamydia
      infection. METHODS: Using data from sexually experienced (>=1 lifetime sexual
      partner) 16-year-old to 24-year-old participants in Britain's third National
      Survey of Sexual Attitudes and Lifestyles (conducted 2010-2012), we explored
      socio-demographic and behavioural factors associated with prevalent chlamydia
      infection (detected in urine; n=1832), self-reported testing and self-reported
      diagnosis in the last year (both n=3115). RESULTS: Chlamydia prevalence was 3.1%
      (95% CI 2.2% to 4.3%) in women and 2.3% (1.5% to 3.4%) in men. A total of 12.3%
      of women and 5.3% men had a previous chlamydia diagnosis. Factors associated with
      prevalent infection were also associated with testing and diagnosis (eg,
      increasing numbers of sexual partners), with some exceptions. For example,
      chlamydia prevalence was higher in women living in more deprived areas, whereas
      testing was not. In men, prevalence was higher in 20-24 than 16-19 year olds but
      testing was lower. Thirty per cent of women and 53.7% of men with >=2 new sexual
      partners in the last year had not recently tested. CONCLUSIONS: In 2010-2012 in
      Britain, the proportion of young adults reporting chlamydia testing was generally
      higher in those reporting factors associated with chlamydia. However, many of
      those with risk factors had not been recently tested, leaving potential for
      undiagnosed infections. Greater screening and prevention efforts among
      individuals in deprived areas and those reporting risk factors for chlamydia may
      reduce undiagnosed prevalence and transmission.

PMID- 26290485
TI  - Literacy and Numeracy Underachievement in Boys and Girls With ADHD.
AB  - OBJECTIVE: The aim was to determine literacy and numeracy outcomes, among
      children with and without ADHD by gestational age and gender. METHOD: De
      identified linked population data from the Western Australian Monitoring of Drugs
      of Dependence System and Western Australian Literacy and Numeracy Assessment
      databases, and the Midwives Notification System used information on 6,819
      children with ADHD compared with 14,451 non-ADHD children. RESULTS: A total of
      23% of boys and 28% of girls with ADHD had numeracy scores below the benchmark in
      School Year 3, compared with 11% of children without ADHD. These differences were
      also evident for reading, writing, and spelling through primary school. Children
      with ADHD and reduced gestational age were at a greater risk of not meeting
      numeracy and reading benchmarks, compared with children born at term. CONCLUSION:
      Children with ADHD are disadvantaged from an early age in key areas of learning,
      and this risk increased with reduction in gestational age at birth.

PMID- 26290486
TI  - Louse-borne relapsing fever (Borrelia recurrentis) in an Eritrean refugee
      arriving in Switzerland, August 2015.
AB  - We report an imported case of louse-borne relapsing fever in a young adult
      Eritrean refugee who presented with fever shortly after arriving in Switzerland.
      Analysis of blood smears revealed spirochetes identified as Borrelia recurrentis
      by 16S rRNA gene sequencing. We believe that louse-borne relapsing fever may be
      seen more frequently in Europe as a consequence of a recent increase in refugees
      from East Africa travelling to Europe under poor hygienic conditions in confined
      spaces.

PMID- 26290487
TI  - Incidence of gonococcal and chlamydial infections and coverage of two laboratory
      surveillance networks, France, 2012.
AB  - Surveillance of sexually transmitted diseases in France is based on voluntary
      networks of laboratories and clinicians. Despite the importance of incidence data
      in improving knowledge about the national context and in international
      comparisons, such data were not previously available. During nationwide quality
      control of laboratories, mandatory for all laboratories, we conducted a survey in
      June 2013 to estimate the incidence rates of gonococcal and chlamydial infections
      for 2012 and to estimate the proportion of diagnoses performed (coverage) by the
      country's two laboratory-based sentinel networks for these diseases. Estimated
      incidence rates for 2012 were 39 per 100,000 persons aged 15 to 59 years for
      gonorrhoea and 257 per 100,000 persons aged 15 to 49 years for chlamydia. These
      rates were consistent with the average levels for a group of other Western
      countries. However, different estimates between countries may reflect disparate
      sources of surveillance data and diverse screening strategies. Better
      comparability between countries requires harmonising data sources and the
      presentation of results. Estimated coverage rates of the gonococcal and
      chlamydial infection surveillance networks in France in 2012 were 23% and 18%,
      respectively, with substantial regional variations. These variations justify
      improving the representativeness of these networks by adding laboratories in
      insufficiently covered areas.

PMID- 26290489
TI  - Authors' correction for Euro Surveill. 2015;20(25).

PMID- 26290488
TI  - Age-related prevalence of cross-reactive antibodies against influenza A(H3N2)
      variant virus, Germany, 2003 to 2010.
AB  - To estimate susceptibility to the swine-origin influenza A(H3N2) variant virus
      (A(H3N2)v) in the German population, we investigated cross-reactive antibodies
      against this virus and factors associated with seroprotective titre using sera
      from representative health examination surveys of children and adolescents (n =
      815, 2003-06) and adults (n = 600, 2008-10). Antibodies were assessed by
      haemagglutination inhibition assay (HI); in our study an HI titre >= 40 was
      defined as seroprotective. We investigated associated factors by multivariable
      logistic regression. Overall, 41% (95% confidence interval (CI): 37-45) of
      children and adolescents and 39% (95% CI: 34-44) of adults had seroprotective
      titres. The proportion of people with seroprotective titre was lowest among
      children younger than 10 years (15%; 95% CI: 7-30) and highest among adults aged
      18 to 29 years (59%; 95% CI: 49-67). Prior influenza vaccination was associated
      with higher odds of having seroprotective titre (odds ratio (OR) for children and
      adolescents: 3.4; 95% CI: 1.8-6.5; OR for adults: 2.4; 95% CI: 1.7-3.4). Young
      children showed the highest and young adults the lowest susceptibility to the
      A(H3N2)v virus. Our results suggest that initial exposure to circulating seasonal
      influenza viruses may predict long-term cross-reactivity that may be enhanced by
      seasonal influenza vaccination.

PMID- 26290491
TI  - Marjolin's ulcer.

PMID- 26290490
TI  - The NEK1 interactor, C21ORF2, is required for efficient DNA damage repair.
AB  - Defective DNA damage response is a threat to genome stability and a proven cause
      of tumorigenesis. C21ORF2 (chromosome 21 open reading frame 2) is a novel gene on
      chromosome 21, and the C21ORF2 protein is found to interact with NEK1. Earlier
      studies showed that C21ORF2 might be associated with some human genetic diseases
      including Down syndrome. However, the cellular functions of C21ORF2 remain
      unknown. In the present study, we reported that C21ORF2 affected cell
      proliferation after DNA damage induced by ionizing radiation, and DNA repair was
      less efficient in C21ORF2-depleted cells compared with control cells. However,
      C21ORF2-knockdown cells did not show defects in the activation of the G2-phase
      DNA damage checkpoint. Furthermore, homologous recombination, but not non
      homologous end joining repair, was found to be impaired after C21ORF2
      attenuation, which could be rescued by the overexpression of NEK1, indicating
      that C21ORF2 functions in the same pathway as NEK1 in DNA damage repair.

PMID- 26290492
TI  - Evidence of Selection for the alpha-Globin Gene Deletions and Triplications in a
      Southern Chinese Population.
AB  - alpha(+)-Thalassemia (alpha(+)-thal) is common in Southern China. The high
      frequency could be due to over dominant selection through malaria. Two molecular
      mechanisms that produce alpha(+)-thal have been defined; one results in the 
      alpha(3.7) (rightward) deletion and reciprocal alphaalphaalpha(anti 3.7)
      triplication, and the other one results in the -alpha(4.2) (leftward) deletion
      and reciprocal alphaalphaalpha(anti 4.2) triplication. Considering that each de
      novo event produced a chromosome with an alpha gene deletion and a chromosome
      with an alpha triplication, if there is no favorable allele, one would expected
      to find the same allelic frequencies. We found a favorable selection for the 
      alpha(3.7) deletion in the Chinese population, and we also found that the alpha
      triplication is not as rare as was first thought, especially for the
      alphaalphaalpha(anti 3.7) triplication. 

PMID- 26290493
TI  - In vivo confocal microscopy of basal cell carcinoma: a systematic review of
      diagnostic accuracy.
AB  - Basal cell carcinoma (BCC) is the most prevalent type of skin cancer. Histologic
      analysis of punch biopsy or direct excision specimen is used to confirm clinical
      diagnosis. In vivo reflectance confocal microscopy (RCM) is a non-invasive
      imaging modality that could facilitate early diagnosis and minimize unnecessary
      invasive procedures. We systematically reviewed diagnostic accuracy (sensitivity
      and specificity) of RCM in diagnosing primary BCCs to judge its usefulness.
      Eligible studies were reviewed for methodological quality using the QUADAS-2
      tool. We used the bivariate random-effects model to calculate summary estimates
      of sensitivity and specificity. Six studies met the selection criteria and were
      included for analysis. The meta-analysis showed a summary estimate of sensitivity
      0.97 (95% CI, 0.90-0.99) and specificity 0.93 (95% CI, 0.88-0.96). All but one of
      the QUADAS-2 items showed a high or unclear risk of bias with regards to patient
      selection. RCM may be a promising diagnostic tool, but the limited number of
      available studies and potential risk of bias of included studies do not allow us
      to draw firm conclusions. Future accuracy studies should take these limitations
      into account. 

PMID- 26290494
TI  - Strategies for decreasing contamination of homemade nasal saline irrigation
      solutions.
AB  - BACKGROUND: Saline nasal irrigations (SNI) are an important adjunct in the
      treatment of rhinosinusitis, and many patients prepare and store these solutions
      in their homes without an awareness of the potential for contamination. The
      objectives of this study were to determine if such contamination occurs and the
      effect of preparation methods on contamination. METHODS: Stock solutions of
      various tonicities and pHs were prepared using boiled, bottled, and distilled
      water (n = 57). The solutions were stored at ambient temperature or refrigerated
      for 1 week. Each day, 50 mL of the solutions were decanted to simulate
      transferring the stock solution into an irrigation vector. Cultures of the stock
      solutions were taken on days 1, 3, and 7. RESULTS: Overall contamination rate was
      35.1%. The boiled water solutions were more likely to demonstrate bacterial
      growth (p < 0.001), as were those that were hypotonic (p = 0.046). pH had no
      significant effect (p = 0.127). Growth occurred as early as 24 hours after
      solution preparation. Pathogenic species isolated were Staphylococcus aureus,
      Moraxella sp, Sphingomonas paucimobilis, Acinetobacter junii, Methylobacterium
      sp, and Brevundimonas diminuta. No bacterial growth occurred in refrigerated
      solutions (p = 0.008). CONCLUSION: Pathogenic bacterial growth can occur in a
      short period of time in homemade SNI solutions with routine handling. Solutions
      should be refrigerated if possible. If solutions are to be stored at ambient
      temperature, they should be either isotonic or hypertonic and prepared from
      bottled or distilled water.

PMID- 26290495
TI  - Sudden-Onset Bilateral Blindness in a Young Girl Receiving Parenteral Nutrition:
      Case Report and Review of Literature.
AB  - BACKGROUND: Parenteral nutrition (PN) via a central venous catheter is routinely
      used for surgical patients without a functioning gastrointestinal tract.
      Complications of PN can be metabolic and thrombotic. Blindness is a rare and
      unexpected complication. CASE: A young female patient with postcorrosive pyloric
      stenosis was started on PN through an indwelling central venous catheter. On the
      sixth day of PN, the patient reported sudden painless bilateral complete loss of
      vision. Examination revealed bilateral normal-sized pupils with normal pupillary
      reaction. There was complete bilateral absence of visual acuity with no
      perception of light. Fundus examination was normal. Magnetic resonance imaging
      revealed an acute infarct in the left occipital lobe, left corpus callosum, and
      posteromedial aspect of the left thalamus. No cardiac source of the thrombus
      could be identified. After supportive treatment, the vision started improving
      after 3 days; recovery was 95% after 10 days. A feeding jejunostomy was performed
      urgently under local anesthesia, and 1 month of enteral nutrition was
      administered. One month after the event, the patient's vision returned to normal.
      Definitive surgery in the form of antrectomy with Billroth II reconstruction was
      performed 8 weeks later. CONCLUSION: Blindness secondary to central venous
      catheterization is very rare; possible mechanisms are venous thrombosis with
      paradoxical emboli, air emboli, or accidental arterial puncture. Clinicians must
      exercise caution while using PN. A high index of suspicion is required to
      diagnose and treat unexpected complications.

PMID- 26290496
TI  - Glucagon signalling in the dorsal vagal complex is sufficient and necessary for
      high-protein feeding to regulate glucose homeostasis in vivo.
AB  - High-protein feeding acutely lowers postprandial glucose concentration compared
      to low-protein feeding, despite a dichotomous rise of circulating glucagon
      levels. The physiological role of this glucagon rise has been largely overlooked.
      We here first report that glucagon signalling in the dorsal vagal complex (DVC)
      of the brain is sufficient to lower glucose production by activating a Gcgr-PKA
      ERK-KATP channel signalling cascade in the DVC of rats in vivo. We further
      demonstrate that direct blockade of DVC Gcgr signalling negates the acute ability
      of high- vs. low-protein feeding to reduce plasma glucose concentration,
      indicating that the elevated circulating glucagon during high-protein feeding
      acts in the brain to lower plasma glucose levels. These data revise the
      physiological role of glucagon and argue that brain glucagon signalling
      contributes to glucose homeostasis during dietary protein intake.

PMID- 26290497
TI  - Outcomes for patients with chronic lymphocytic leukemia and acute leukemia or
      myelodysplastic syndrome.
AB  - Acute leukemia (AL) and myelodysplastic syndrome (MDS) are uncommon in chronic
      lymphocytic leukemia (CLL). We retrospectively identified 95 patients with CLL,
      also diagnosed with AL (n=38) or MDS (n=57), either concurrently (n=5) or
      subsequent (n=90) to CLL diagnosis and report their outcomes. Median number of
      CLL treatments prior to AL and MDS was 2 (0-9) and 1 (0-8), respectively; the
      most common regimen was purine analog combined with alkylating agent+/-CD20
      monoclonal antibody. Twelve cases had no prior CLL treatment. Among 38 cases with
      AL, 33 had acute myelogenous leukemia (AML), 3 had acute lymphoid leukemia (ALL;
      1 Philadelphia chromosome positive), 1 had biphenotypic and 1 had extramedullary
      (bladder) AML. Unfavorable AML karyotype was noted in 26, and intermediate risk
      in 7 patients. There was no association between survival from AL and number of
      prior CLL regimens or karyotype. Expression of CD7 on blasts was associated with
      shorter survival. Among MDS cases, all International Prognostic Scoring System
      (IPSS) were represented; karyotype was unfavorable in 36, intermediate in 6 and
      favorable in 12 patients; 10 experienced transformation to AML. Shorter survival
      from MDS correlated with higher risk IPSS, poor-risk karyotype and increased
      number of prior CLL treatments. Overall, outcomes for patients with CLL
      subsequently diagnosed with AL or MDS were very poor; AL/MDS occurred without
      prior CLL treatment. Effective therapies for these patients are desperately
      needed. 

PMID- 26290499
TI  - Ketamine's potential as a rapid antidepressant was overplayed.

PMID- 26290500
TI  - Implementation of a pilot telehealth programme in community palliative care: A
      qualitative study of clinicians' perspectives.
AB  - BACKGROUND: Telehealth technologies are an emerging resource opening up the
      possibility of greater support if they have utility for patients, carers and
      clinicians. They may also help to meet health systems' imperatives for improved
      service delivery within current budgets. Clinicians' experiences and attitudes
      play a key role in the implementation of any innovation in service delivery. AIM:
      To explore clinicians' perspectives on and experiences of the utilisation of a
      pilot telehealth model and its integration into a specialist community palliative
      care programme. DESIGN: Focus groups and interviews generated data that were
      analysed through the lens of a realistic evaluation theoretical framework.
      SETTING/PARTICIPANTS: The study was conducted in a metropolitan specialist
      palliative care service in South Australia. Participants (n = 10) were clinicians
      involved in the delivery of community specialist palliative care and the piloting
      of a telehealth programme. RESULTS: Service providers consider telehealth
      resources as a means to augment current service provision in a complementary way
      rather than as a replacement for face-to-face assessments. Introducing this
      technology, however, challenged the team to critically explore aspects of current
      service provision. The introduction of technologies also has the potential to
      alter the dynamic of relationships between patients and families and community
      palliative care clinicians. CONCLUSION: Implementation of a pilot telehealth
      programme in a specialist palliative community team needs to involve clinical
      staff in service redesign from the outset. Reliable IT infrastructure and
      technical support is critical for telehealth models to be effective and will aid
      uptake.

PMID- 26290498
TI  - A High Through-put Platform for Recombinant Antibodies to Folded Proteins.
AB  - Antibodies are key reagents in biology and medicine, but commercial sources are
      rarely recombinant and thus do not provide a permanent and renewable resource.
      Here, we describe an industrialized platform to generate antigens and validated
      recombinant antibodies for 346 transcription factors (TFs) and 211 epigenetic
      antigens. We describe an optimized automated phage display and antigen expression
      pipeline that in aggregate produced about 3000 sequenced Fragment antigen-binding
      domain that had high affinity (typically EC50<20 nm), high stability (Tm~80 
      degrees C), good expression in E. coli (~5 mg/L), and ability to bind antigen in
      complex cell lysates. We evaluated a subset of Fabs generated to homologous SCAN
      domains for binding specificities. These Fragment antigen-binding domains were
      monospecific to their target SCAN antigen except in rare cases where they cross
      reacted with a few highly related antigens. Remarkably, immunofluorescence
      experiments in six cell lines for 270 of the TF antigens, each having multiple
      antibodies, show that ~70% stain predominantly in the cytosol and ~20% stain in
      the nucleus which reinforces the dominant role that translocation plays in TF
      biology. These cloned antibody reagents are being made available to the academic
      community through our web site recombinant-antibodies.org to allow a more system
      wide analysis of TF and chromatin biology. We believe these platforms,
      infrastructure, and automated approaches will facilitate the next generation of
      renewable antibody reagents to the human proteome in the coming decade. 

PMID- 26290502
TI  - Mucocutaneous lesions in free-ranging Atlantic bottlenose dolphins Tursiops
      truncatus from the southeastern USA.
AB  - Mucocutaneous lesions were biopsied from free-ranging Atlantic bottlenose
      dolphins Tursiops truncatus inhabiting the Indian River Lagoon (IRL), Florida,
      and estuarine waters of Charleston (CHS), South Carolina, USA, between 2003 and
      2013. A total of 78 incisional biopsies from 58 dolphins (n=43 IRL, n=15 CHS)
      were examined. Thirteen dolphins had 2 lesions biopsied at the same examination,
      and 6 dolphins were re-examined and re-biopsied at time intervals varying from 1
      to 8 yr. Biopsy sites included the skin (n=47), tongue (n=2), and genital mucosa
      (n=29). Pathologic diagnoses were: orogenital sessile papilloma (39.7%),
      cutaneous lobomycosis (16.7%), tattoo skin disease (TSD; 15.4%), nonspecific
      chronic to chronic-active dermatitis (15.4%), and epidermal hyperplasia (12.8%).
      Pathologic diagnoses from dolphins with 2 lesions were predominately orogenital
      sessile papillomas (n=9) with nonspecific chronic to chronic-active dermatitis
      (n=4), TSD (n=3), lobomycosis (n=1), and epidermal hyperplasia (n=1). Persistent
      pathologic diagnoses from the same dolphins re-examined and re-biopsied at
      different times included genital sessile papillomas (n=3), lobomycosis (n=2), and
      nonspecific dermatitis (n=2). This is the first study documenting the various
      types, combined prevalence, and progression of mucocutaneous lesions in dolphins
      from the southeastern USA. The data support other published findings describing
      the health patterns in dolphins from these geographic regions. Potential health
      impacts related to the observed suite of lesions are important for the IRL and
      CHS dolphin populations, since previous studies have indicated that both
      populations are affected by complex infectious diseases often associated with
      immunologic disturbances and anthropogenic contaminants.

PMID- 26290503
TI  - Case descriptions of fibropapillomatosis in rehabilitating loggerhead sea turtles
      Caretta caretta in the southeastern USA.
AB  - Fibropapillomatosis (FP) is a debilitating neoplastic disease that affects all
      species of hard-shelled sea turtles, including loggerhead turtles Caretta
      caretta. FP can represent an important clinical concern in rehabilitating
      turtles, since managing these infectious lesions often requires special husbandry
      provisions including quarantine, and FP may affect clinical progression, extend
      rehabilitation duration, and complicate prognoses. Here we describe cases of
      rehabilitating loggerhead turtles with FP (designated FP+). Medical records of
      FP+ loggerhead cases from 3 sea turtle rehabilitation facilities in the
      southeastern USA were reviewed. Between 2001 and 2014, FP was observed in 8 of
      818 rehabilitating loggerhead turtles (0.98% overall prevalence in admitted
      patients). FP+ loggerhead size classes represented were large juvenile (straight
      carapace length, SCL: 58.1-80 cm; n=7) and adult (SCL>87 cm; n=1). Three turtles
      presented with FP, and 5 developed tumors during rehabilitation within a range of
      45 to 319 d. Sites of new tumor growth included the eyes, sites of trauma, neck,
      and glottis. FP+ turtles were scored as mildly (3/8), moderately (4/8), or
      heavily (1/8) afflicted. The mean total time in rehabilitation was 476+/-355 d
      (SD) (range: 52-1159 d). Six turtles were released without visible evidence of
      FP, 1 turtle was released with mild FP, and 1 turtle with internal FP was
      euthanized. Clinical decision-making for FP+ loggerhead patients can be aided by
      such information as time to tumor development, anatomic locations to monitor for
      new tumor growth, husbandry considerations, diagnostic and treatment options, and
      comparisons to FP in rehabilitating green turtles Chelonia mydas.

PMID- 26290504
TI  - Health condition of juvenile Chelonia mydas related to fibropapillomatosis in
      southeast Brazil.
AB  - Packed cell volume (PCV), plasma biochemistry, visual body condition (BC), and
      calculated body condition index (BCI) were evaluated in 170 wild juvenile green
      sea turtles Chelonia mydas from an aggregation in the effluent canal of a steel
      mill in Brazil. Occurrence of cutaneous fibropapillomatosis (FP) was observed in
      44.1% of the animals examined. BCI alone did not differ significantly between
      healthy animals and those afflicted with FP. However, all turtles with low BCI
      were severely afflicted and were uremic, hypoglycemic, and anemic in relation to
      healthy animals. Severe FP was not always reflected by a poor health condition of
      the individual. Clinical evaluation and plasma biochemistry indicated that most
      animals afflicted with FP were in good health condition. Differences in FP
      manifestations and associated health conditions in different geographic regions
      must be assessed by long-term health monitoring programs to help define
      priorities for conservation efforts. 

PMID- 26290505
TI  - Pathogenicity in six Australian reptile species following experimental
      inoculation with Bohle iridovirus.
AB  - Ranaviruses are able to infect multiple species of fish, amphibian and reptile,
      and some strains are capable of interclass transmission. These numerous potential
      carriers and reservoir species compound efforts to control and contain infections
      in cultured and wild populations, and a comprehensive knowledge of susceptible
      species and life stage is necessary to inform such processes. Here we report on
      the challenge of 6 water-associated reptiles with Bohle iridovirus (BIV) to
      investigate its potential pathogenicity in common native reptiles of the aquatic
      and riparian fauna of northern Queensland, Australia. Adult tortoises Elseya
      latisternum and Emydura krefftii, snakes Boiga irregularis, Dendrelaphis
      punctulatus and Amphiesma mairii, and yearling crocodiles Crocodylus johnstoni
      were exposed via intracoelomic inoculation or co-habitation with infected con
      specifics, but none were adversely affected by the challenge conditions applied
      here. Bohle iridovirus was found to be extremely virulent in hatchling tortoises
      E. latisternum and E. krefftii via intracoelomic challenge, as demonstrated by
      distinct lesions in multiple organs associated with specific immunohistochemistry
      staining and a lethal outcome (10/17) of the challenge. Virus was re-isolated
      from 2/5 E. latisternum, 4/12 E. krefftii and 1/3 brown tree snakes B.
      irregularis. Focal necrosis, haemorrhage and infiltration of granulocytes were
      frequently observed histologically in the pancreas, liver and sub-mucosa of the
      intestine of challenged tortoise hatchlings. Immunohistochemistry demonstrated
      the presence of ranavirus antigens in the necrotic lesions and in individual
      cells of the vascular endothelium, the connective tissue and in granulocytes
      associated with necrosis or present along serosal surfaces. The outcome of this
      study confirms hatchling tortoises are susceptible to BIV, thereby adding
      Australian reptiles to the host range of ranaviruses. Additionally, given that
      BIV was originally isolated from an amphibian, our study provides additional
      evidence that interclass transmission of ranavirus may occur in the wild. 

PMID- 26290501
TI  - The 8q24 rs6983267G variant is associated with increased thyroid cancer risk.
AB  - The G allele of the rs6983267 single-nucleotide polymorphism, located on
      chromosome 8q24, has been associated with increased risk of several cancer types.
      The association between rs6983267G and thyroid cancer (TC) has been tested in
      different populations, mostly of European ancestry, and has led to inconclusive
      results. While significant associations have been reported in the British and
      Polish populations, no association has been detected in populations from Spain,
      Italy and the USA. To further investigate the role of rs6983267G in TC
      susceptibility, we evaluated rs6983267 genotypes in three populations of
      different continental ancestry (British Isles, Colombia and Japan), providing a
      total of 3067 cases and 8575 controls. We detected significant associations
      between rs6983267G and TC in the British Isles (odds ratio (OR)=1.19, 95% CI:
      1.11-1.27, P=4.03*10(-7)), Japan (OR=1.20, 95% CI: 1.03-1.41, P=0.022) and a
      borderline significant association of similar effect direction and size in
      Colombia (OR=1.19, 95% CI: 0.99-1.44, P=0.069). A meta-analysis of our multi
      ethnic study and previously published non-overlapping datasets, which included a
      total of 5484 cases and 12 594 controls, confirmed the association between
      rs6983267G and TC (P=1.23*10(-7), OR=1.13, 95% CI: 1.08-1.18). Our results
      therefore support the notion that rs6983267G is a bona fide TC risk variant that
      increases the risk of disease by ~13%. 

PMID- 26290506
TI  - Patterns of Batrachochytrium dendrobatidis transmission between tadpoles in a
      high-elevation rainforest stream in tropical Australia.
AB  - The highly virulent fungal pathogen Batrachochytrium dendrobatidis (Bd) poses a
      global threat to amphibian biodiversity. Streams and other water bodies are
      central habitats in the ecology of the disease, particularly in rainforests where
      they may transport and transmit the pathogen and harbor infected tadpoles that
      serve as reservoir hosts. We conducted an experiment using larval green-eyed tree
      frogs Litoria serrata in semi-natural streamside channels to test the hypotheses
      that (1) the fungus can be transmitted downstream in stream habitats and (2)
      infection affects tadpole growth and mouthpart loss. Our results showed that
      transmission can occur downstream in flowing water with no contact between
      individuals, that newly infected tadpoles suffered increased mouthpart loss in
      comparison with controls that were never infected and that infected tadpoles grew
      at reduced rates. Although recently infected tadpoles showed substantial loss of
      mouthparts, individuals with longstanding infections did not, suggesting that
      mouthparts may re-grow following initial loss. Our study suggests that any
      management efforts that can reduce the prevalence of infections in tadpoles may
      be particularly effective if applied in headwater areas, as their effects are
      likely to be felt downstream. 

PMID- 26290507
TI  - In vitro characteristics of cyprinid herpesvirus 2: effect of kidney extract
      supplementation on growth.
AB  - Herpesviral hematopoietic necrosis caused by goldfish hematopoietic necrosis
      virus (now identified as cyprinid herpesvirus 2, CyHV-2) has contributed to
      economic losses in goldfish Carassius auratus culture and is becoming a major
      obstacle in Prussian carp C. gibelio aquaculture in China. Several reports have
      described difficulties in culturing the virus, with the total loss of infectivity
      within several passages in cell culture. We succeeded in propagating CyHV-2 with
      a high infectious titer in a RyuF-2 cell line newly derived from the fin of the
      Ryukin goldfish variety using culture medium supplemented with 0.2% healthy
      goldfish kidney extract. The addition of kidney extract to the medium enabled
      rapid virus growth, resulting in the completion of cytopathic effect (CPE) within
      4 to 6 d at 25 degrees C. The extract also enabled reproducible virus culture
      with a titer of 105-6 TCID50 ml-1. The virus cultured using this protocol showed
      pathogenicity in goldfish after intraperitoneal injection. The virus grew in RyuF
      2 cells at 15, 20, 25, 30, and 32 degrees C but not at 34 degrees C or higher.
      Higher incubation temperatures allowed earlier development of CPE, but culture at
      30 and 32 degrees C yielded a lower virus titer than that obtained at other
      temperatures because of heat inactivation of the propagated virus during
      cultivation. Cell lines derived from goldfish and ginbuna C. langsdorfii showed
      high susceptibility to the virus; cell lines from carp were susceptible to the
      virus using a medium containing goldfish kidney extract, but EPC, FHM, and BF-2
      cell lines did not produce any CPE, even in the presence of the extract. 

PMID- 26290508
TI  - Identification and genetic characterization of Piscirickettsia salmonis in native
      fish from southern Chile.
AB  - Piscirickettsia salmonis is the etiological agent of piscirickettsiosis, a severe
      disease causing high mortalities in salmonids. This bacterium has been previously
      identified and isolated in all cultivated salmonids in Chile and worldwide,
      including Salmo salar, Oncorhynchus kisutch, and O. mykiss, in addition to being
      found in non-salmonid species such as Dicentrarchus labrax and Atractoscion
      nobilis. In this study, the 16S rRNA gene and intergenic spacer ITS-1 of P.
      salmonis were amplified by PCR from DNA samples extracted from the native Chilean
      fish species Eleginops maclovinus, Odontesthes regia, Sebastes capensis, and
      Salilota australis. Analysis of the 16S rRNA sequences from O. regia demonstrated
      a close phylogenetic relationship with the 16S rRNA gene in the Chilean EM-90
      strain. The 16S rRNA sequences from E. maclovinus, S. capensis, and S. australis
      were related to the Chilean LF-89 sequence and Scottish strains. To confirm these
      findings, analysis of P. salmonis ITS-1 sequences obtained from the 4 sampled
      native species demonstrated a high degree of identity and a close phylogenetic
      relationship with Chilean P. salmonis sequences, including LF-89 and EM-90. These
      results suggest a strong relationship between the nucleotide sequences from the
      16S rRNA and ITS-1 genes amplified from native fish with those sequences
      described in the first P. salmonis strains to be identified and isolated in
      Chile. 

PMID- 26290509
TI  - Genotyping of virulence plasmid from Vibrio parahaemolyticus isolates causing
      acute hepatopancreatic necrosis disease in shrimp.
AB  - Acute hepatopancreatic necrosis disease (AHPND) has caused severe mortalities in
      farmed penaeid shrimp throughout SE Asia and Mexico. The causative agent of AHPND
      is the marine bacterium Vibrio parahaemolyticus, which secretes PirA- and PirB
      like binary toxin that caused deterioration in the hepatopancreas of infected
      shrimp. The genes responsible for the production of this toxin are located in a
      large plasmid residing within the bacterial cells. We analyzed the plasmid
      sequence from the whole genome sequences of AHPND-V. parahaemolyticus isolates
      and identified 2 regions that exhibit a clear geographical variation: a 4243-bp
      Tn3-like transposon and a 9-bp small sequence repeat (SSR). The Tn3-like
      transposon was only found in the isolates from Mexico and 2 unspecified Central
      American countries, but not in SE Asian isolates from China, Vietnam, and
      Thailand. We developed PCR methods to characterize AHPND-V. parahaemolyticus
      isolates as either Mexican-type or SE Asian-type based on the presence of the Tn3
      like transposon. The SSR is found within the coding region of a hypothetical
      protein and has either 4, 5, or 6 repeat units. SSRs with 4 repeat units were
      found in isolates from Vietnam, China, and Thailand. SSRs with 5 repeat units
      were found in some Vietnamese isolates, and SSRs with 6 repeat units were only
      found in the Mexican isolates. 

PMID- 26290510
TI  - Encystment and excystment of kinetoplastid Azumiobodo hoyamushi, causal agent of
      soft tunic syndrome in ascidian aquaculture.
AB  - Soft tunic syndrome in the edible ascidian Halocynthia roretzi is caused by the
      kinetoplastid flagellate Azumiobodo hoyamushi, which was found to assume a
      fusiform cell form with 2 flagella in axenic, pure culture. When the flagellate
      form was incubated in sterilized artificial seawater (pH 8.4), some of the cells
      became cyst-like and adhered to the bottom of the culture plate. The cyst-like
      forms were spherical or cuboidal, and each had 2 flagella encapsulated in its
      cytoplasm. Encystment was also induced in culture medium alkalified to the pH of
      seawater (8.4) but not in unmodified (pH 7.2) or acidified media (pH 6.4). More
      than 95% of the cyst-like cells converted to the flagellate form within 1 d
      following transfer to seawater containing ascidian tunic extracts from host
      ascidians. The cyst-like cells were able to survive in seawater with no added
      nutrients for up to 2 wk at 20 degrees C and for a few months at 5 to 15 degrees
      C. The survival period in seawater depended on temperature: some cyst-like cells
      survived 3 mo at 10 degrees C, and ca. 95% of these converted to flagellate forms
      in seawater containing tunic extracts. Thus, A. hoyamushi is able to persist
      under adverse conditions in a cyst-like form able to adhere to organic and
      inorganic substrata for protracted periods of time. 

PMID- 26290511
TI  - New yellow head virus genotype (YHV7) in giant tiger shrimp Penaeus monodon
      indigenous to northern Australia.
AB  - In 2012, giant tiger shrimp Penaeus monodon originally sourced from Joseph
      Bonaparte Gulf in northern Australia were examined in an attempt to identify the
      cause of elevated mortalities among broodstock at a Queensland hatchery. Nucleic
      acid extracted from ethanol-fixed gills of 3 individual shrimp tested positive
      using the OIE YHV Protocol 2 RT-PCR designed to differentiate yellow head virus
      (YHV1) from gill-associated virus (GAV, synonymous with YHV2) and the OIE YHV
      Protocol 3 RT-nested PCR designed for consensus detection of YHV genotypes.
      Sequence analysis of the 794 bp (Protocol 2) and 359 bp (Protocol 3) amplicons
      from 2 distinct regions of ORF1b showed that the yellow-head-complex virus
      detected was novel when compared with Genotypes 1 to 6. Nucleotide identity on
      the Protocol 2 and Protocol 3 ORF1b sequences was highest with the highly
      pathogenic YHV1 genotype (81 and 87%, respectively) that emerged in P. monodon in
      Thailand and lower with GAV (78 and 82%, respectively) that is enzootic to P.
      monodon inhabiting eastern Australia. Comparison of a longer (725 bp) ORF1b
      sequence, spanning the Protocol 3 region and amplified using a modified YH30/31
      RT-nPCR, provided further phylogenetic evidence for the virus being distinct from
      the 6 described YHV genotypes. The virus represents a unique seventh YHV genotype
      (YHV7). Despite the mortalities observed, the role of YHV7 remains unknown. 

PMID- 26290513
TI  - The presence of primary sclerosing cholangitis in patients with ileal pouch anal-
      anastomosis is associated with an additional risk for vitamin D deficiency.
AB  - OBJECTIVE: Vitamin D deficiency is common in patients with ileal pouch-anal
      anastomosis (IPAA) for ulcerative colitis (UC). Whether vitamin D levels are
      further lowered in patients with concomitant IPAA and primary sclerosing
      cholangitis (PSC) is not known. The aim of this study was to evaluate the
      presence of PSC as a risk factor for vitamin D deficiency in patients with UC and
      IPAA. METHODS: In this case control study, 74 patients with concurrent IPAA and
      PSC were included in the study group, and 79 patients with IPAA, but without PSC,
      served as controls. Forty-four variables were analyzed. Univariate analysis and
      multivariate analysis with stepwise logistic regression were performed. RESULTS:
      A total 153 eligible patients were included, with 74 (48.4%) in the study group
      and 79 (51.6%) in the control group. Vitamin D level in the study group was 18.9
      +/- 1.4 ng/dL compared with 30.3 +/- 1.7 ng/d in the control group (P = 0.011).
      Vitamin D deficiency (<= 20 ng/dL) was present in 65 (42.5%) patients. PSC
      occurred in 49 (75.4%) of the 65 patients with vitamin D deficiency. In the
      multivariate analysis, only the presence of PSC (odds ratio [OR]: 7.56; 95%
      confidence interval [CI]: 2.39-24.08; P = 0.001) and vitamin D supplementation
      (OR: 2.58; 95% CI: 1.57-9.19; P = 0.018) remained associated with vitamin D
      deficiency. CONCLUSION: The presence of PSC was found to be an independent risk
      factor for vitamin D deficiency in UC patients with IPAA. These patients should
      be routinely screened and closely monitored for vitamin D deficiency.

PMID- 26290512
TI  - Neoadjuvant chemoradiation therapy and pathological complete response in rectal
      cancer.
AB  - The management of rectal cancer has evolved significantly in the last few
      decades. Significant improvements in local disease control were achieved in the
      1990s, with the introduction of total mesorectal excision and neoadjuvant
      radiotherapy. Level 1 evidence has shown that, with neoadjuvant chemoradiation
      therapy (CRT) the rates of local recurrence can be lower than 6% and, as a
      result, neoadjuvant CRT currently represents the accepted standard of care. This
      approach has led to reliable tumor down-staging, with 15-27% patients with a
      pathological complete response (pCR)-defined as no residual cancer found on
      histological examination of the specimen. Patients who achieve pCR after CRT have
      better long-term outcomes, less risk of developing local or distal recurrence and
      improved survival. For all these reasons, sphincter-preserving procedures or
      organ-preserving options have been suggested, such as local excision of residual
      tumor or the omission of surgery altogether. Although local recurrence rate has
      been stable at 5-6% with this multidisciplinary management method, distal
      recurrence rates for locally-advanced rectal cancers remain in excess of 25% and
      represent the main cause of death in these patients. For this reason, more recent
      trials have been looking at the administration of full-dose systemic chemotherapy
      in the neoadjuvant setting (in order to offer early treatment of disseminated
      micrometastases, thus improving control of systemic disease) and selective use of
      radiotherapy only in non-responders or for low rectal tumors smaller than 5 cm. 

PMID- 26290514
TI  - Serum trough infliximab and anti-infliximab antibodies in a cohort of
      gastroenterology and rheumatology patients' infliximab therapeutic drug
      monitoring.
AB  - BACKGROUND: Infliximab, a monoclonal antibody directed against tumour necrosis
      factor, is widely used in the treatment of chronic inflammatory conditions
      including Crohn's disease and rheumatoid arthritis. Its use is limited by
      development of anti-infliximab antibodies, which can lead to loss of therapeutic
      efficacy. Serum infliximab and anti-infliximab antibody measurements have
      recently become routinely available in the UK. The study aimed to assess the
      clinical utility of antibodies as an adjunct to trough infliximab. METHODS: Serum
      trough infliximab was measured in 201 samples from 108 gastroenterology and
      rheumatology patients on maintenance infliximab therapy. Results were correlated
      with C-reactive protein concentrations. Total anti-infliximab antibodies were
      measured in 164 samples. RESULTS: The median (25th-75th percentile) trough
      infliximab was 3.7 ug/mL (1.2-5.2 ug/mL) and 23% of samples had a concentration
      <=1 ug/mL. A notable proportion had positive anti-infliximab antibodies: 84/164
      (51%), which subdivided to 85% and 28% with infliximab <=1 and >1 ug/mL,
      respectively.Serum C-reactive protein was found to be significantly higher where
      infliximab was <=1 compared to >1 ug/mL (10 mg/L [<5-24 mg/L] vs. <5 mg/L [<5-8
      mg/L], P < 0.01), although a strict correlation was not observed. The
      relationship between trough infliximab and C-reactive protein differed depending
      on antibody status and there was no association between C-reactive protein and
      the presence or absence of antibodies. CONCLUSION: Our findings support
      measurement of anti-infliximab antibodies only in the context of low infliximab
      concentrations <1 ug/mL. A higher therapeutic cut-off may be relevant in patients
      with negative antibodies. Further work is indicated to investigate the clinical
      significance of positive antibodies with therapeutic infliximab concentrations.

PMID- 26290515
TI  - microRNA expression in blood of dengue patients.
AB  - BACKGROUND: Dengue is the most common arboviral illness worldwide. While most
      infected patients recover, a proportion of them develop severe complications or
      fatality. Nevertheless, the pathophysiological mechanisms which distinguish the
      disease severity and associated complications are not clearly understood. We
      studied blood profiles of dengue patients in order to identify microRNAs that
      could play a role in these pathophysiological mechanisms. METHODS: Blood samples
      from 26 dengue-infected patients were collected within 0-14 days of infection.
      Together with samples obtained from six healthy individuals, microRNA profiles
      were generated to identify significantly altered microRNAs upon dengue infection.
      Profiles of patients with influenza were also used to determine the disease
      specificity of these altered microRNAs. Their discriminative power to distinguish
      dengue from influenza was then tested statistically. RESULTS: Several
      significantly altered microRNAs were identified in patients with dengue. Twelve
      microRNAs were specifically altered upon acute dengue whereas 14 microRNAs
      exhibited similar expression between dengue and influenza. Seventeen microRNAs
      which could potentially distinguish dengue-related complications were also
      identified. Expression of miR-24-1-5p, miR-512-5p and miR-4640-3p distinguished
      mild dengue from those exhibiting liver complications whereas miR-383 was
      significantly upregulated in mild dengue compared to those diagnosed as severe
      dengue with fluid accumulation. CONCLUSIONS: We identified two panels of
      microRNAs - one specific for dengue and the other common to dengue and influenza.
      We also report on the differentially expressed microRNAs in patients with mild
      versus severe dengue, which could be the basis for the complications seen in
      them.

PMID- 26290516
TI  - Using a decellularized splenic matrix as a 3D scaffold for hepatocyte cultivation
      in vitro: a preliminary trial.
AB  - Using a decellularized liver matrix (DLM) to reengineer liver tissue is a
      promising therapy for end-stage liver disease. However, the limited supply of
      donor organs still hampers its potential clinical application, while a xenogenic
      decellularized matrix may bring a risk of zoonosis and immunological rejection.
      Therefore, an appropriate alternative scaffold is needed. In this research, we
      established a decellularized splenic matrix (DSM) in a rodent model, which
      preserved the 3D ultrastructure, the components of the extracellular matrix (ECM)
      and the native vascular network. The DSM and DLM had similar components of ECM,
      and similar mechanical properties. Hepatocytes were seeded to the DSM and DLM for
      dynamic culturing up to 6 d, and distributed both in decellularized sinusoidal
      spaces and around the vessels. The TUNEL-positive cell percentage in a dynamic
      culturing decellularized splenic matrix (dDSM) was 10.7%  +/-  3.6% at 3d and
      25.8%  +/-  5.6% at 5d, although 14.2%  +/-  4.5% and 24.8%  +/-  2.9%,
      respectively, in a dynamic culturing decellularized liver matrix (dDLM) at the
      same time point (p  >  0.05). Primary hepatocytes in the dDSM and dDLM expressed
      albumin, G6pc and Ugt1a1. The gene expression of Cyp2b1, Cyp1a2 and HNF1alpha in
      the gene transcription level revealed hepatocytes had lower gene expression
      levels in the dDSM compared with the dDLM at 3d, but better than those in a
      sandwich culture. The cumulative albumin production at 6 d of culture was 80.7  
      +/-   9.6 MUg per million cells in the dDSM and 89.6   +/-   4.6 MUg per million
      cells in the dDLM (p  >  0.05). In summary, the DSM is a promising 3D scaffold
      for hepatocyte cultivation in vitro. 

PMID- 26290517
TI  - Assisted dying: law and practice around the world.

PMID- 26290518
TI  - 'One-stop' visits for insertion of intrauterine contraception using online
      resources.

PMID- 26290520
TI  - Climbing Back Up the Mountain: Reflections From an Exploration of End-of-Life
      Needs of Persons Living With HIV/AIDS in Appalachian Tennessee.
AB  - Little is known about the health access and end-of-life (EOL) concerns of persons
      living with HIV/AIDS (PLWHA) in Appalachia, where religious and cultural values
      are largely traditional. A qualitative, descriptive study with 9 participants was
      undertaken to assess EOL care needs among those from South Central Appalachian
      PLWHA. The focus of the study was to examine subjective data regarding EOL needs
      assessment related to advanced care planning. Five men and 4 women self
      acknowledged a diagnosis of HIV/AIDS and completed a 2-hour face-to-face
      interview with the nurse researcher. Data were analyzed using qualitative
      descriptive content analysis methods, including data coding for emergent themes
      and metaphors. A common metaphor tied content to both struggle and triumph as
      well as the beauty and ruggedness of the Appalachian region: "Climbing Back up
      the Mountain." Rich descriptions of the significance of the metaphor match with
      stigma as the greatest hurdle to overcome in planning and interacting with
      others, including health care providers and significant others, about EOL care
      needs and advanced planning preferences. Further, the metaphor was derived
      directly from quotes offered by participants. Sources of stigma were often
      intersecting: the disease itself, associations with "promiscuity," sexual
      minority status, illicit drug use, and so on. Strong spiritual images were
      contrasted with a common avoidance and disdain of organized religion. Findings
      were used in refining plans for a larger study of EOL care needs and concerns on
      the population of PLWHA in 2 Southern Appalachian states. Comparison with other
      research and insights for providers is included.

PMID- 26290521
TI  - The role of point defects in PbS, PbSe and PbTe: a first principles study.
AB  - Intrinsic defects are of central importance to many physical and chemical
      processes taking place in compound nanomaterials, such as photoluminescence,
      accommodation of off-stoichiometry and cation exchange. Here, the role of
      intrinsic defects in the above mentioned processes inside rock salt (RS) lead
      chalcogenide systems PbS, PbSe and PbTe (PbX) was studied systematically using
      first principles density functional theory. Vacancy, interstitial, Schottky and
      Frenkel defects were considered. Rock salt PbO was included for comparison. The
      studied physical properties include defect formation energy, local geometry
      relaxation, Bader charge analysis, and electronic structure. The defect formation
      energies show that monovacancy defects and Schottky defects are favoured over
      interstitial and Frenkel defects. Schottky dimers, where the cation vacancy and
      anion vacancy are adjacent to each other, have the lowest defect formation
      energies at 1.27 eV, 1.29 eV and 1.21 eV for PbS, PbSe and PbTe, respectively.
      Our results predict that a Pb monovacancy gives rise to a shallow acceptor state,
      while an X vacancy generates a deep donor state, and Schottky defects create
      donor-acceptor pairs inside the band gap. The surprisingly low formation energy
      of Schottky dimers suggests that they may play an important role in cation
      exchange processes, in contrast to the current notion that only single point
      defects migrate during cation exchange. 

PMID- 26290522
TI  - Running With the Pack: Teen Peer-Relationship Qualities as Predictors of Adult
      Physical Health.
AB  - This study assessed qualities of adolescent peer relationships as long-term
      predictors of physical health quality in adulthood. In an intensive multimethod,
      multireporter study of a community sample of 171 individuals assessed repeatedly
      from the ages of 13 to 27 years, physical health quality in adulthood was
      robustly predicted by independent reports of early-adolescent close-friendship
      quality and by a pattern of acquiescence to social norms in adolescent peer
      relationships. Predictions remained after accounting for numerous potential
      confounds, including prior health problems, concurrent body mass index, anxious
      and depressive symptoms, personality characteristics, adolescent-era financial
      adversity, and adolescent-era physical attractiveness. These findings have
      important implications for understanding the unique intensity of peer
      relationships in adolescence. 

PMID- 26290519
TI  - A Presynaptic Regulatory System Acts Transsynaptically via Mon1 to Regulate
      Glutamate Receptor Levels in Drosophila.
AB  - Mon1 is an evolutionarily conserved protein involved in the conversion of Rab5
      positive early endosomes to late endosomes through the recruitment of Rab7. We
      have identified a role for Drosophila Mon1 in regulating glutamate receptor
      levels at the larval neuromuscular junction. We generated mutants in Dmon1
      through P-element excision. These mutants are short-lived with strong motor
      defects. At the synapse, the mutants show altered bouton morphology with several
      small supernumerary or satellite boutons surrounding a mature bouton; a
      significant increase in expression of GluRIIA and reduced expression of
      Bruchpilot. Neuronal knockdown of Dmon1 is sufficient to increase GluRIIA levels,
      suggesting its involvement in a presynaptic mechanism that regulates postsynaptic
      receptor levels. Ultrastructural analysis of mutant synapses reveals
      significantly smaller synaptic vesicles. Overexpression of vglut suppresses the
      defects in synaptic morphology and also downregulates GluRIIA levels in Dmon1
      mutants, suggesting that homeostatic mechanisms are not affected in these
      mutants. We propose that DMon1 is part of a presynaptically regulated
      transsynaptic mechanism that regulates GluRIIA levels at the larval neuromuscular
      junction. 

PMID- 26290523
TI  - A Difference-Education Intervention Equips First-Generation College Students to
      Thrive in the Face of Stressful College Situations.
AB  - A growing social psychological literature reveals that brief interventions can
      benefit disadvantaged students. We tested a key component of the theoretical
      assumption that interventions exert long-term effects because they initiate
      recursive processes. Focusing on how interventions alter students' responses to
      specific situations over time, we conducted a follow-up lab study with students
      who had participated in a difference-education intervention 2 years earlier. In
      the intervention, students learned how their social-class backgrounds mattered in
      college. The follow-up study assessed participants' behavioral and hormonal
      responses to stressful college situations. We found that difference-education
      participants discussed their backgrounds in a speech more frequently than control
      participants did, an indication that they retained the understanding of how their
      backgrounds mattered. Moreover, among first-generation students (i.e., students
      whose parents did not have 4-year degrees), those in the difference-education
      condition showed greater physiological thriving (i.e., anabolic-balance
      reactivity) than those in the control condition, which suggests that they
      experienced their working-class backgrounds as a strength. 

PMID- 26290524
TI  - The relationship between treatment attendance, adherence, and outcome in a
      caregiver-mediated intervention for low-resourced families of young children with
      autism spectrum disorder.
AB  - Rates of participation in intervention research have not been extensively studied
      within autism spectrum disorder. Such research is important given the benefit of
      early intervention on long-term prognosis for children with autism spectrum
      disorder. The goals of this study were to examine how family demographic factors
      predicted treatment attendance and adherence in a caregiver-mediated randomized
      controlled trial targeting core deficits of autism spectrum disorder, and whether
      treatment attendance and adherence predicted outcome. In all, 147 caregiver-child
      dyads from a low-resourced population were randomized to in-home caregiver
      mediated module or group-based caregiver education module treatment. Treatment
      attendance, adherence, and outcome (time spent in joint engagement) were the
      primary outcome variables. The majority of families who entered treatment (N =
      87) maintained good attendance. Attendance was significantly predicted by
      socioeconomic status, site, and treatment condition. Families in caregiver
      mediated module reported lower levels of treatment adherence, which was
      significantly predicted by site, condition, caregiver stress, and child nonverbal
      intelligence quotient. Dyads in caregiver-mediated module had significantly
      longer interactions of joint engagement, which was significantly predicted by an
      interaction between treatment attendance and condition. Overall, the results from
      this study stress the importance of considering demographic variables in research
      design when considering barriers to treatment attendance and adherence.

PMID- 26290526
TI  - An emerging role of pendrin in health and disease.

PMID- 26290525
TI  - Regulation of gastric epithelial cell homeostasis by gastrin and bone
      morphogenetic protein signaling.
AB  - We reported that transgenic expression of the bone morphogenetic protein (BMP)
      signaling inhibitor noggin in the mouse stomach, leads to parietal-cell (PC)
      loss, expansion of transitional cells expressing markers of both mucus neck and
      zymogenic lineages, and to activation of proliferative mechanisms. Because these
      cellular changes were associated with increased levels of the hormone gastrin, we
      investigated if gastrin mediates the expression of the phenotypic changes of the
      noggin transgenic mice (NogTG mice). Three-month-old NogTG mice were crossed to
      gastrin-deficient (GasKO mice) to generate NogTG;GasKO mice. Morphology of the
      corpus of wild type, NogTG, GasKO, and NogTG;GasKO mice was analyzed by H&E
      staining. Distribution of PCs and zymogenic cells (ZCs) was analyzed by
      immunostaining for the H(+)/K(+)-ATPase and intrinsic factor (IF). Expression of
      the H(+)/K(+)-ATPase and IF genes and proteins were measured by QRT-PCR and
      western blots. Cell proliferation was assessed by immunostaining for
      proliferating cell nuclear antigen. The corpus of the NogTG;GasKO mice displayed
      a marked reduction in the number of PCs and ZCs in comparison to NogTG mice.
      Further, cellular proliferation was significantly lower in NogTG;GasKO mice, than
      in the NogTG mice. Thus, gastrin mediates the increase in gastric epithelial cell
      proliferation induced by inhibition of BMP signaling in vivo. Moreover, gastrin
      and BMP signaling exert cooperative effects on the maturation and differentiation
      of both the zymogenic and PC lineages. These findings contribute to a better
      understanding of the factors involved in the control of gastric epithelial cell
      homeostasis. 

PMID- 26290527
TI  - Does wearing clothing made of a synthetic "cooling" fabric improve indoor cycle
      exercise endurance in trained athletes?
AB  - This randomized, double-blind, crossover study examined the effects of a clothing
      ensemble made of a synthetic fabric promoted as having superior cooling
      properties (COOL) on exercise performance and its physiological and perceptual
      determinants during cycle exercise in ambient laboratory conditions that mimic
      environmental conditions of indoor training/sporting facilities. Twenty athletes
      (15 men:5 women) aged 25.8 +/- 1.2 years (mean +/- SEM) with a maximal rate of O2
      consumption of 63.7 +/- 1.5 mL.kg(-1).min(-1) completed cycle exercise testing at
      85% of their maximal incremental power output to exhaustion while wearing an
      ensemble consisting of a fitted long-sleeved shirt and full trousers made of
      either COOL or a synthetic control fabric (CTRL). Exercise endurance time was not
      different under COOL versus CTRL conditions: 12.38 +/- 0.98 versus 11.75 +/- 1.10
      min, respectively (P > 0.05). Similarly, COOL had no effect on detailed
      thermoregulatory (skin and esophageal temperatures), cardiometabolic,
      ventilatory, and perceptual responses to exercise (all P > 0.05). In conclusion,
      clothing made of a synthetic fabric with purported "cooling" properties did not
      improve high-intensity cycle exercise endurance in trained athletes under ambient
      laboratory conditions that mimic the environmental conditions of indoor
      training/sporting facilities. 

PMID- 26290528
TI  - The effect of intraocular and intracranial pressure on retinal structure and
      function in rats.
AB  - An increasing number of studies indicate that the optic nerve head of the eye is
      sensitive not only to changes in intraocular pressure (IOP), but also to
      intracranial pressure (ICP). This study examines changes to optic nerve and
      retinal structure in a rat model in response to a range of IOP and ICP levels
      using optical coherence tomography. Furthermore, we examine the functional
      sequelae of these structural changes by quantifying the effect of pressure
      changes on the electroretinogram. IOP elevation (10-90 mmHg) induces progressive
      deformation of the optic nerve head and retinal surface (P < 0.05), compression
      of the retina (P < 0.05) and bipolar cell (b-wave), and retinal ganglion cell
      (scotopic threshold response) dysfunction (P < 0.05). Simultaneously altering ICP
      (-5 to 30 mmHg) modifies these IOP-induced responses, with lower ICP (-5 mmHg)
      exacerbating and higher ICP (15-30 mmHg) ameliorating structural and functional
      deficits. Thus, the balance between IOP and ICP (optic nerve pressure gradient,
      ONPG = IOP - ICP) plays an important role in optic nerve integrity. Structural
      and functional parameters exhibit a two-phase relationship to ONPG, with
      structural changes being more sensitive to ONPG modification (threshold = -0.6 to
      11.3 mmHg) compared with functional changes (threshold = 49.7-54.6 mmHg). These
      findings have implications for diseases including glaucoma, intracranial
      hypertension, and long-term exposure to microgravity. 

PMID- 26290529
TI  - Circulating angiotensin II deteriorates left ventricular function with
      sympathoexcitation via brain angiotensin II receptor.
AB  - Sympathoexcitation contributes to the progression of heart failure. Activation of
      brain angiotensin II type 1 receptors (AT1R) causes central sympathoexcitation.
      Thus, we assessed the hypothesis that the increase in circulating angiotensin II
      comparable to that reported in heart failure model affects cardiac function
      through the central sympathoexcitation via activating AT1R in the brain. In
      Sprague-Dawley rats, the subcutaneous infusion of angiotensin II for 14 days
      increased the circulating angiotensin II level comparable to that reported in
      heart failure model rats after myocardial infarction. In comparison with the
      control, angiotensin II infusion increased 24 hours urinary norepinephrine
      excretion, and systolic blood pressure. Angiotensin II infusion hypertrophied
      left ventricular (LV) without changing chamber dimensions while increased end
      diastolic pressure. The LV pressure -: volume relationship indicated that
      angiotensin II did not impact on the end-systolic elastance, whereas
      significantly increased end-diastolic elastance. Chronic intracerebroventricular
      infusion of AT1R blocker, losartan, attenuated these angiotensin II-induced
      changes. In conclusion, circulating angiotensin II in heart failure is capable of
      inducing sympathoexcitation via in part AT1R in the brain, subsequently leading
      to LV diastolic dysfunction. 

PMID- 26290530
TI  - The effect of acute and long-term physical activity on extracellular matrix and
      serglycin in human skeletal muscle.
AB  - Remodeling of extracellular matrix (ECM), including regulation of proteoglycans
      in skeletal muscle can be important for physiological adaptation to exercise. To
      investigate the effects of acute and long-term exercise on the expression of ECM
      related genes and proteoglycans in particular, 26 middle-aged, sedentary men
      underwent a 12 weeks supervised endurance and strength training intervention and
      two acute, 45 min bicycle tests (70% VO2max), one at baseline and one after 12
      weeks of training. Total gene expression in biopsies from m. vastus lateralis was
      measured with deep mRNA sequencing. After 45 min of bicycling approximately 550
      gene transcripts were >50% upregulated. Of these, 28 genes (5%) were directly
      related to ECM. In response to long-term exercise of 12 weeks 289 genes exhibited
      enhanced expression (>50%) and 20% of them were ECM related. Further analyses of
      proteoglycan mRNA expression revealed that more than half of the proteoglycans
      expressed in muscle were significantly enhanced after 12 weeks intervention. The
      proteoglycan serglycin (SRGN) has not been studied in skeletal muscle and was one
      of few proteoglycans that showed increased expression after acute (2.2-fold, P <
      0.001) as well as long-term exercise (1.4-fold, P < 0.001). Cultured, primary
      human skeletal muscle cells expressed and secreted SRGN. When the expression of
      SRGN was knocked down, the expression and secretion of serpin E1 (SERPINE1)
      increased. In conclusion, acute and especially long-term exercise promotes
      enhanced expression of several ECM components and proteoglycans. SRGN is a novel
      exercise-regulated proteoglycan in skeletal muscle with a potential role in
      exercise adaptation. 

PMID- 26290531
TI  - The noncarbonic anhydrase inhibiting acetazolamide analog N-methylacetazolamide
      reduces the hypercapnic, but not hypoxic, ventilatory response.
AB  - Previous studies have shown that the carbonic anhydrase (CA) inhibitors
      acetazolamide (AZ) and methazolamide (MZ) have inhibiting actions on breathing.
      Classically these have been attributed to CA inhibition, but other effects
      unrelated to CA inhibition have been identified in other tissues. To explore this
      possibility in the control of ventilation by the central nervous system, we
      investigated whether an AZ-analog without CA inhibiting properties, by virtue of
      a single methylation on the sulfonamide moiety, N-methylacetazolamide (NMA),
      would still display similar actions to acetazolamide and methazolamide. NMA (20
      mg kg(-1)) was given intravenously to anesthetized cats and we measured the
      responses to steady-state isocapnic hypoxia and stepwise changes in end-tidal
      pco2 before and after infusion of this AZ analog using the technique of end-tidal
      forcing. NMA caused a large decrease in the apneic threshold and CO2 sensitivity
      very similar to those previously observed with AZ and MZ, suggesting that these
      effects are mediated independently of CA inhibition. In contrast to
      acetazolamide, but similar to methazolamide, NMA did not affect the steady-state
      isocapnic hypoxic response. In conclusion, our data reveal complex effects of
      sulfonamides with very similar structure to AZ that reveal both CA-dependent and
      CA-independent effects, which need to be considered when using AZ as a probe for
      the role of CA in the control of ventilation. 

PMID- 26290532
TI  - Stretch-induced increase in cardiac contractility is independent of myocyte Ca2+
      while block of stretch channels by streptomycin improves contractility after
      ischemic stunning.
AB  - Stretching the cardiac left ventricle (LV) enhances contractility but its effect
      on myoplasmic [Ca(2+)] is controversial. We measured LV pressure (LVP) and
      [Ca(2+)] as a function of intra-LV stretch in guinea pig intact hearts before and
      after 15 min global stunning +/- perfusion with streptomycin (STM), a stretch
      activated channel blocker. LV wall [Ca(2+)] was measured by indo-1 fluorescence
      and LVP by a saline-filled latex balloon inflated in 50 MUL steps to stretch the
      LV. We implemented a mathematical model to interpret cross-bridge dynamics and
      myofilament Ca(2+) responsiveness from the instantaneous relationship between
      [Ca(2+)] and LVP +/- stretching. We found that: (1) stretch enhanced LVP but not
      [Ca(2+)] before and after stunning in either control (CON) and STM groups, (2)
      after stunning [Ca(2+)] increased in both groups although higher in STM versus
      CON (56% vs. 39%), (3) STM-enhanced LVP after stunning compared to CON (98% vs.
      76% of prestunning values), and (4) stretch-induced effects on LVP were
      independent of [Ca(2+)] before or after stunning in both groups. Mathematical
      modeling suggested: (1) cooperativity in cross-bridge kinetics and myofilament
      Ca(2+) handling is reduced after stunning in the unstretched heart, (2) stunning
      results in depressed myofilament Ca(2+) sensitivity in the presence of attached
      cross-bridges regardless of stretch, and (3) the initial mechanism responsible
      for increased contractility during stretch may be enhanced formation of cross
      bridges. Thus stretch-induced enhancement of contractility is not due to
      increased [Ca(2+)], whereas enhanced contractility after stunning in STM versus
      CON hearts results from improved Ca(2+) handling and/or enhanced actinomyosin
      cross-bridge cycling. 

PMID- 26290533
TI  - Diet-induced obesity promotes altered remodeling and exacerbated cardiac
      hypertrophy following pressure overload.
AB  - Heart failure (HF) is the end stage of cardiovascular disease, in which
      hypertrophic remodeling no longer meets cardiac output demand. Established animal
      models of HF have provided insights into disease pathogenesis. However, these
      models are developed on dissimilar metabolic backgrounds from humans - patients
      with HF are frequently overweight or obese, whereas animal models of HF are
      typically lean. Thus, we aimed to develop and investigate model for cardiac
      hypertrophy and failure that also recapitulates the cardiometabolic state of HF
      in humans. We subjected mice with established diet-induced obesity (DIO) to
      cardiac pressure overload provoked by transverse aortic constriction (TAC).
      Briefly, we fed WT male mice a normal chow or high-fat diet for 10 weeks prior to
      sham/TAC procedures and until surgical follow-up. We then analyzed cardiac
      hypertrophy, mechanical function, and electrophysiology at 5-6 weeks after
      surgery. In DIO mice with TAC, hypertrophy and systolic dysfunction were
      exacerbated relative to chow TAC animals, which showed minimal remodeling with
      our moderate constriction intensity. Normalized heart weight was 55.8% greater
      and fractional shortening was 30.9% less in DIO TAC compared with chow TAC
      hearts. However, electrophysiologic properties were surprisingly similar between
      DIO sham and TAC animals. To examine molecular pathways activated by DIO and TAC,
      we screened prohypertrophic signaling cascades, and the exacerbated remodeling
      was associated with early activation of the c-Jun-N-terminal kinase (JNK1/2)
      signaling pathway. Thus, DIO aggravates the progression of hypertrophy and HF
      caused by pressure overload, which is associated with JNK1/2 signaling, and
      cardiometabolic state can significantly modify HF pathogenesis. 

PMID- 26290534
TI  - Sleep onset hypoventilation in chronic spinal cord injury.
AB  - A high prevalence of sleep-disordered breathing (SDB) after spinal cord injury
      (SCI) has been reported in the literature; however, the underlying mechanisms are
      not well understood. We sought to determine the effect of the withdrawal of the
      wakefulness drive to breathe on the degree of hypoventilation in SCI patients and
      able-bodied controls. We studied 18 subjects with chronic cervical and thoracic
      SCI (10 cervical, 8 thoracic SCI; 11 males; age 42.4 +/- 17.1 years; body mass
      index 26.3 +/- 4.8 kg/m(2)) and 17 matched able-bodied subjects. Subjects
      underwent polysomnography, which included quantitative measurement of
      ventilation, timing, and upper airway resistance (RUA) on a breath-by-breath
      basis during transitions from wake to stage N1 sleep. Compared to able-bodied
      controls, SCI subjects had a significantly greater reduction in tidal volume
      during the transition from wake to N1 sleep (from 0.51 +/- 0.21 to 0.32 +/- 0.10
      L vs. 0.47 +/- 0.13 to 0.43 +/- 0.12 L; respectively, P < 0.05). Moreover, end
      tidal CO2 and end-tidal O2 were significantly altered from wake to sleep in SCI
      (38.9 +/- 2.7 mmHg vs. 40.6 +/- 3.4 mmHg; 94.1 +/- 7.1 mmHg vs. 91.2 +/- 8.3
      mmHg; respectively, P < 0.05), but not in able-bodied controls (39.5 +/- 3.2 mmHg
      vs. 39.9 +/- 3.2 mmHg; 99.4 +/- 5.4 mmHg vs. 98.9 +/- 6.1 mmHg; respectively, P =
      ns). RUA was not significantly altered in either group. In conclusion,
      individuals with SCI experience hypoventilation at sleep onset, which cannot be
      explained by upper airway mechanics. Sleep onset hypoventilation may contribute
      to the development SDB in the SCI population. 

PMID- 26290535
TI  - Genome-wide annotation of microRNA primary transcript structures reveals novel
      regulatory mechanisms.
AB  - Precise regulation of microRNA (miRNA) expression is critical for diverse
      physiologic and pathophysiologic processes. Nevertheless, elucidation of the
      mechanisms through which miRNA expression is regulated has been greatly hindered
      by the incomplete annotation of primary miRNA (pri-miRNA) transcripts. While a
      subset of miRNAs are hosted in protein-coding genes, the majority of pri-miRNAs
      are transcribed as poorly characterized noncoding RNAs that are 10's to 100's of
      kilobases in length and low in abundance due to efficient processing by the
      endoribonuclease DROSHA, which initiates miRNA biogenesis. Accordingly, these
      transcripts are poorly represented in existing RNA-seq data sets and exhibit
      limited and inaccurate annotation in current transcriptome assemblies. To
      overcome these challenges, we developed an experimental and computational
      approach that allows genome-wide detection and mapping of pri-miRNA structures.
      Deep RNA-seq in cells expressing dominant-negative DROSHA resulted in much
      greater coverage of pri-miRNA transcripts compared with standard RNA-seq. A
      computational pipeline was developed that produces highly accurate pri-miRNA
      assemblies, as confirmed by extensive validation. This approach was applied to a
      panel of human and mouse cell lines, providing pri-miRNA transcript structures
      for 1291/1871 human and 888/1181 mouse miRNAs, including 594 human and 425 mouse
      miRNAs that fall outside protein-coding genes. These new assemblies uncovered
      unanticipated features and new potential regulatory mechanisms, including links
      between pri-miRNAs and distant protein-coding genes, alternative pri-miRNA
      splicing, and transcripts carrying subsets of miRNAs encoded by polycistronic
      clusters. These results dramatically expand our understanding of the organization
      of miRNA-encoding genes and provide a valuable resource for the study of
      mammalian miRNA regulation. 

PMID- 26290536
TI  - Tandem repeat variation in human and great ape populations and its impact on gene
      expression divergence.
AB  - Tandem repeats (TRs) are stretches of DNA that are highly variable in length and
      mutate rapidly. They are thus an important source of genetic variation. This
      variation is highly informative for population and conservation genetics. It has
      also been associated with several pathological conditions and with gene
      expression regulation. However, genome-wide surveys of TR variation in humans and
      closely related species have been scarce due to technical difficulties derived
      from short-read technology. Here we explored the genome-wide diversity of TRs in
      a panel of 83 human and nonhuman great ape genomes, in a total of six different
      species, and studied their impact on gene expression evolution. We found that
      population diversity patterns can be efficiently captured with short TRs (repeat
      unit length, 1-5 bp). We examined the potential evolutionary role of TRs in gene
      expression differences between humans and primates by using 30,275 larger TRs
      (repeat unit length, 2-50 bp). Genes that contained TRs in the promoters, in
      their 3' untranslated region, in introns, and in exons had higher expression
      divergence than genes without repeats in the regions. Polymorphic small repeats
      (1-5 bp) had also higher expression divergence compared with genes with fixed or
      no TRs in the gene promoters. Our findings highlight the potential contribution
      of TRs to human evolution through gene regulation. 

PMID- 26290537
TI  - Small RNA Derived from the Virulence Modulating Region of the Potato spindle
      tuber viroid Silences callose synthase Genes of Tomato Plants.
AB  - The tomato (Solanum lycopersicum) callose synthase genes CalS11-like and CalS12
      like encode proteins that are essential for the formation of callose, a major
      component of pollen mother cell walls; these enzymes also function in callose
      formation during pathogen infection. This article describes the targeting of
      these callose synthase mRNAs by a small RNA derived from the virulence modulating
      region of two Potato spindle tuber viroid variants. More specifically, viroid
      infection of tomato plants resulted in the suppression of the target mRNAs up to
      1.5-fold, depending on the viroid variant used and the gene targeted. The
      targeting of these mRNAs by RNA silencing was validated by artificial microRNA
      experiments in a transient expression system and by RNA ligase-mediated rapid
      amplification of cDNA ends. Viroid mutants incapable of targeting callose
      synthase mRNAs failed to induce typical infection phenotypes, whereas a chimeric
      viroid obtained by swapping the virulence modulating regions of a mild and a
      severe variant of Potato spindle tuber viroid greatly affected the accumulation
      of viroids and the severity of disease symptoms. These data provide evidence of
      the silencing of multiple genes by a single small RNA derived from a viroid. 

PMID- 26290538
TI  - Association of Physical Activity History With Physical Function and Mortality in
      Old Age.
AB  - BACKGROUND: We examined whether physical activity in early adulthood, late
      midlife, and old age as well as cumulative physical activity history are
      associated with changes in physical functioning and mortality in old age.
      METHODS: Data are from participants aged 65 years or older enrolled in the
      InCHIANTI study who were followed up from 1998-2000 to 2007-2008 (n = 1,149). At
      baseline, participants recalled their physical activity levels at ages 20-40, 40
      60, and in the previous year, and they were categorized as physically inactive,
      moderately active, and physically active. Physical performance was assessed with
      the Short Physical Performance Battery and self-reported mobility disability was
      evaluated at the 3-, 6- and 9-year follow-up. Mortality follow-up was assessed
      until the end of 2010. RESULTS: Physical inactivity at baseline was associated
      with greater decline in Short Physical Performance Battery score (mean 9-year
      change: -2.72, 95% CI: -3.08, -2.35 vs -0.98, 95% -1.57, -0.39) and greater rate
      of incident mobility disability (hazard ratio 4.66, 95% CI 1.14-19.07) and
      mortality (hazard ratio 2.18, 95% CI 1.01-4.70) compared to physically active
      participants at baseline. Being physically active throughout adulthood was
      associated with smaller decline in physical performance as well as with lower
      risk of incident mobility disability and premature death compared with those who
      had been less active during their adult life. CONCLUSIONS: Higher cumulative
      physical activity over the life course was associated with less decline in
      physical performance and reduced rate of incident mobility disability and
      mortality in older ages.

PMID- 26290539
TI  - Application of Optical Topometry to Analysis of the Plant Epidermis.
AB  - The plant epidermis regulates key physiological functions contributing to
      photosynthetic rate, plant productivity, and ecosystem stability. Yet,
      quantitative characterization of this interface between a plant and its aerial
      environment is laborious and destructive with current techniques, making large
      scale characterization of epidermal cell parameters impractical. Here, we present
      our exploration of optical topometry (OT) for the analysis of plant organ
      surfaces. OT is a mature, confocal microscopy-based implementation of surface
      metrology that generates nanometer-scale digital characterizations of any
      surface. We report epidermal analyses in Arabidopsis (Arabidopsis thaliana) and
      other species as well as dried herbarium specimens and fossilized plants. We
      evaluate the technology's analytical potential for identifying an array of
      epidermal characters, including cell type distributions, variation in cell
      morphology and stomatal depth, differentiation of herbarium specimens, and real
      time deformations in living tissue following detachment. As applied to plant
      material, OT is very fast and nondestructive, yielding richly mineable data sets
      describing living tissues and rendering a variety of their characteristics
      accessible for statistical, quantitative genetic, and structural analysis. 

PMID- 26290540
TI  - Chronic Disease Self-Management by People With HIV.
AB  - As HIV has transitioned into a chronic disease, reappraisal of clinical
      management has occurred with chronic disease self-management (CDSM) as one
      possibility. However, despite extensive work on CDSM across a range of diseases,
      little attention has focused on psychosocial contexts of the lives of people for
      whom programs are intended. This article reports semi-structured interviews used
      to explore health practices and motivations of 33 people with HIV (PWHIV) in
      Australia. Within participants' accounts, different forms of subjectivity and
      agency emerged with implications for how they understood and valued health
      related behaviors. Four themes arose: health support and disclosure, social
      support and stigma, employment/structure, and health decisions beyond HIV. The
      experience of stigma and its intersection with CDSM remains relatively un
      chartered. This study found stigma shapes agency and engagement with health.
      Decisions concerning health behaviors are often driven by perceived social and
      emotional benefit embedded in concerns of disclosure and stigma.

PMID- 26290541
TI  - Talking About Looking: Three Approaches to Interviewing Carers of People With
      Rheumatoid Arthritis About Information Seeking.
AB  - Given the profusion of illness-related information, in this article, we consider
      how talking about information seeking-and in particular Internet use-is
      difficult, not because it is necessarily a highly sensitive topic (though it may
      be), but rather due to the unusual and unfamiliar situation of talking about
      information seeking. Drawing on interviews conducted as part of a study on the
      educational needs of carers of people with rheumatoid arthritis, we compare three
      types of interview for understanding online information seeking: interviews
      (recall), researcher-led observation (joining participant at the computer), and
      diaries. We discuss the strengths and weaknesses of each approach and discuss how
      changing interview questions and the form of interaction can help to produce
      different types of data, and potentially more meaningful insights. Of the three
      approaches, conducting interviews with participants while looking at a computer
      (talking while looking) offered the best opportunities to understand Internet
      based information seeking.

PMID- 26290542
TI  - Refugees, Post-Migration Stress, and Internet Use: A Qualitative Analysis of
      Intercultural Adjustment and Internet Use Among Iraqi and Sudanese Refugees to
      the United States.
AB  - Post-migration stressors represent significant obstacle to refugee adjustment,
      and continued exposure to post-migration stressors can negatively affect mental
      and physical health. Communities of support maintained over the Internet may
      provide a sense of constancy and reliability that may insulate against the
      negative effects of stress. We conducted five focus group interviews with Iraqi
      and Sudanese refugees to understand how refugees use the Internet to access
      support in their daily lives. Four trends were observed: (a) Internet use was
      related to culture of origin, (b) refugees were reluctant to explore online, (c)
      children served as brokers of online knowledge, and (d) limited Internet access
      is associated with increased time and financial obligations. This study aims to
      contribute to theory on Internet-mediated social support and to refugee health by
      creating smoother pathways to self-sufficiency and allowing refugees to exhibit
      agency in constructing and maintaining online networks of support. 

PMID- 26290543
TI  - Conflicted Identification in the Sex Education Classroom: Balancing Professional
      Values With Organizational Mandates.
AB  - Despite enormous resources spent on sex education, the United States faces an
      epidemic of unplanned pregnancy and sexually transmitted infections among young
      people. Little research has examined the role sex educators play in alleviating
      or exacerbating this problem. In this study, we interviewed 50 sex educators
      employed by public schools throughout a Midwestern, U.S. state about their
      experiences in the sex education classroom. Twenty-two interviewees communicated
      feelings of conflicted identification and provided examples of the ways in which
      they experienced this subjectivity in the context of their employment. We find
      these interviews shed light on the as-yet-understudied communicative experience
      of conflicted identification by delineating key sources of such conflict and
      discursive strategies used in its negotiation. Our results suggest that those who
      experience conflicted identification and who have a sense of multiple or nested
      identifications within their overarching professional identity may be safeguarded
      to some extent from eventual organizational disidentification. 

PMID- 26290545
TI  - How do we address the disconnect between genetic and morphological diversity in
      germplasm collections?

PMID- 26290546
TI  - Temperature-assisted redistribution of carbohydrates in trees.

PMID- 26290547
TI  - Morphological diversity and evolution of Centrolepidaceae (Poales), a species
      poor clade with diverse body plans and developmental patterns.
AB  - * PREMISE OF THE STUDY: The small primarily Australian commelinid monocot family
      Centrolepidaceae displays remarkably high structural diversity that has been
      hitherto relatively poorly explored. Data on Centrolepidaceae are important for
      comparison with other Poales, including grasses and sedges.* METHODS: We examined
      vegetative and reproductive morphology in a global survey of Centrolepidaceae
      based on light and scanning electron microscopy of 18 species, representing all
      three genera. We used these data to perform a cladistic analysis to assess
      character evolution.* KEY RESULTS: Each of the three genera is monophyletic;
      Centrolepis is sister to Aphelia. Some Centrolepidaceae show a change from spiral
      to distichous phyllotaxy on inflorescence transition. In Aphelia and most species
      of Centrolepis, several morphologically distinct leaf types develop along the
      primary shoot axis and flowers are confined to dorsiventral lateral spikelets.
      Centrolepis racemosa displays secondary unification of programs of leaf
      development, absence of the leaf hyperphyll and loss of shoot dimorphism.
      Presence or absence of a leaf ligule and features of inflorescence and flower
      morphology are useful as phylogenetic characters in Centrolepidaceae.*
      CONCLUSIONS: Ontogenetic changes in phyllotaxy differ fundamentally between some
      Centrolepidaceae and many grasses. Inferred evolutionary transformations of
      phyllotaxy in Centrolepidaceae inflorescences also differ from those in grasses.
      In contrast with grasses, some Centrolepidaceae possess ligulate leaves where the
      ligule represents the boundary between the bifacial hypophyll and unifacial
      hyperphyll. All the highly unusual features of the morphological-misfit species
      Centrolepis racemosa could result from the same saltational event.
      Centrolepidaceae offer good perspectives for studies of evolutionary
      developmental biology.

PMID- 26290548
TI  - Distribution of gelatinous fibers in seedling roots of living cycads.
AB  - * PREMISE OF THE STUDY: The presence of gelatinous (tension) fibers (GFs) in the
      roots of two extant cycadales (Cycas and Zamia) in a recent publication raises
      interesting issues of GF distribution in seed plants. An immediate question that
      arises from this discovery is whether GFs occur consistently in the radicle of
      all extant cycad genera and therefore might have a similar role in root
      contraction. We present results of a survey of nursery-grown material of all 10
      genera.* METHODS: We sequentially sectioned seedling root material and used
      simple staining and histochemical methods to follow anatomical changes along the
      radicle of all 10 genera.* KEY RESULTS: We found GFs in nine genera; Stangeria
      appears to be the only genus without them. In all genera, there is a wide
      variation in the number of GFs and also variation in the development of
      thickened, fleshy roots. "Tertiary expansion" is a useful term to describe late
      cell division and enlargement of both primary and secondary parenchyma, the
      latter produced by the vascular cambium. Certain other histological features can
      be diagnostically useful at the generic level.* CONCLUSIONS: The functional
      interpretation of GFs as being wholly responsible for apparent tissue contraction
      is now somewhat compromised, especially as distortion of tracheary elements by
      changes in dimensions of parenchyma cells can falsely suggest root contraction
      when it may not occur. These preliminary results point the way to a more precise
      investigation of study material grown in more uniform environments using advanced
      technological methods.

PMID- 26290549
TI  - Stepwise evolution of corolla symmetry in CYCLOIDEA2-like and RADIALIS-like gene
      expression patterns in Lamiales.
AB  - * PREMISE OF THE STUDY: CYCLOIDEA2 (CYC2)-like and RADIALIS (RAD)-like genes are
      needed for the normal development of corolla bilateral symmetry in Antirrhinum
      majus L. (snapdragon, Plantaginaceae, Lamiales). However, if and how changes in
      expression of CYC2-like and RAD-like genes correlate with the origin of corolla
      bilateral symmetry early in Lamiales remains largely unknown. The asymmetrical
      expression of CYC2-like and/or RAD-like genes during floral meristem development
      could be ancestral or derived in Plantaginaceae.* METHODS: We used in situ RNA
      localization to examine the expression of CYC2-like and RAD-like genes in two
      early-diverging Lamiales.* KEY RESULTS: CYC2-like and RAD-like genes are
      expressed broadly in the floral meristems in early-diverging Lamiales with
      radially symmetrical corollas, in contrast to their restricted expression in
      adaxial/lateral regions in core Lamiales. The expression pattern of CYC2-like
      genes has evolved in stepwise fashion, in that CYC2-like genes are likely
      expressed briefly in the floral meristem during flower development in sampled
      Oleaceae; prolonged expression of CYC2-like genes in petals originated in the
      common ancestor of Tetrachondraceae and core Lamiales, and asymmetrical
      expression in adaxial/lateral petals appeared later, in the common ancestor of
      the core Lamiales. Likewise, expression of RAD-like genes in petals appeared in
      early-diverging Lamiales or earlier; asymmetrical expression in adaxial/lateral
      petals then appeared in core Lamiales.* CONCLUSIONS: These data plus published
      reports of CYC2-like and RAD-like genes show that asymmetrical expression of
      these two genes is likely derived and correlates with the origins of corolla
      bilateral symmetry.

PMID- 26290550
TI  - Long-term shifts in the phenology of rare and endemic Rocky Mountain plants.
AB  - * PREMISE OF THE STUDY: Mountainous regions support high plant productivity,
      diversity, and endemism, yet are highly vulnerable to climate change. Historical
      records and model predictions show increasing temperatures across high elevation
      regions including the Southern Rocky Mountains, which can have a strong influence
      on the performance and distribution of montane plant species. Rare plant species
      can be particularly vulnerable to climate change because of their limited
      abundance and distribution.* METHODS: We tracked the phenology of rare and
      endemic species, which are identified as imperiled, across three different
      habitat types with herbarium records to determine if flowering time has changed
      over the last century, and if phenological change was related to shifts in
      climate.* KEY RESULTS: We found that the flowering date of rare species has
      accelerated 3.1 d every decade (42 d total) since the late 1800s, with plants in
      sagebrush interbasins showing the strongest accelerations in phenology. High
      winter temperatures were associated with the acceleration of phenology in low
      elevation sagebrush and barren river habitats, whereas high spring temperatures
      explained accelerated phenology in the high elevation alpine habitat. In
      contrast, high spring temperatures delayed the phenology of plant species in the
      two low-elevation habitats and precipitation had mixed effects depending on the
      season.* CONCLUSIONS: These results provide evidence for large shifts in the
      phenology of rare Rocky Mountain plants related to climate, which can have strong
      effects on plant fitness, the abundance of associated wildlife, and the future of
      plant conservation in mountainous regions.

PMID- 26290551
TI  - Climate reconstruction analysis using coexistence likelihood estimation (CRACLE):
      a method for the estimation of climate using vegetation.
AB  - * PREMISE OF THE STUDY: Plant distributions have long been understood to be
      correlated with the environmental conditions to which species are adapted.
      Climate is one of the major components driving species distributions. Therefore,
      it is expected that the plants coexisting in a community are reflective of the
      local environment, particularly climate.* METHODS: Presented here is a method for
      the estimation of climate from local plant species coexistence data. The method,
      Climate Reconstruction Analysis using Coexistence Likelihood Estimation (CRACLE),
      is a likelihood-based method that employs specimen collection data at a global
      scale for the inference of species climate tolerance. CRACLE calculates the
      maximum joint likelihood of coexistence given individual species climate
      tolerance characterization to estimate the expected climate.* KEY RESULTS: Plant
      distribution data for more than 4000 species were used to show that this method
      accurately infers expected climate profiles for 165 sites with diverse climatic
      conditions. Estimates differ from the WorldClim global climate model by less than
      1.5 degrees C on average for mean annual temperature and less than ~250 mm for
      mean annual precipitation. This is a significant improvement upon other plant
      based climate-proxy methods.* CONCLUSIONS: CRACLE validates long hypothesized
      interactions between climate and local associations of plant species.
      Furthermore, CRACLE successfully estimates climate that is consistent with the
      widely used WorldClim model and therefore may be applied to the quantitative
      estimation of paleoclimate in future studies.

PMID- 26290552
TI  - Interactions between plant size and canopy openness influence vital rates and
      life-history tradeoffs in two neotropical understory herbs.
AB  - * PREMISE OF THE STUDY: For tropical forest understory plants, the ability to
      grow, survive, and reproduce is limited by the availability of light. The extent
      to which reproduction incurs a survival or growth cost may change with light
      availability, plant size, and adaptation to shade, and may vary among similar
      species.* METHODS: We estimated size-specific rates of growth, survival, and
      reproduction (vital rates), for two neotropical understory herbs (order
      Zingiberales) in a premontane tropical rainforest in Costa Rica. During three
      annual censuses we monitored 1278 plants, measuring leaf area, number of
      inflorescences, and canopy openness. We fit regression models of all vital rates
      and evaluated them over a range of light levels. The best fitting models were
      selected using Akaike's Information Criterion.* KEY RESULTS: All vital rates were
      significantly influenced by size in both species, but not always by light.
      Increasing light resulted in higher growth and a higher probability of
      reproduction in both species, but lower survival in one species. Both species
      grew at small sizes but shrank at larger sizes. The size at which shrinkage began
      differed among species and light environments. Vital rates of large individuals
      were more sensitive to changes in light than small individuals.* CONCLUSIONS:
      Increasing light does not always positively influence vital rates; the extent to
      which light affects vital rates depends on plant size. Differences among species
      in their abilities to thrive under different light conditions and thus occupy
      distinct niches may contribute to the maintenance of species diversity.

PMID- 26290554
TI  - What causes female bias in the secondary sex ratios of the dioecious woody shrub
      Salix sitchensis colonizing a primary successional landscape?
AB  - * PREMISE OF THE STUDY: Females often outnumber males in Salix populations,
      although the mechanisms behind female bias are not well understood and could be
      caused by both genetic and ecological factors. We investigated several ecological
      factors that could bias secondary sex ratios of Salix sitchensis colonizing Mount
      St. Helens after the 1980 eruption.* METHODS: We determined whether S. sitchensis
      secondary sex ratios varied across disturbance zones created by the eruption and
      across mesic and hydric habitats within each zone. For one population, we tracked
      adult mortality, whole-plant reproductive allocation, the number of stems, and
      plant size for 2 years. In a field experiment, we created artificial streams to
      test whether vegetative reproduction via stem fragments was sex-biased.* KEY
      RESULTS: We found a consistent 2:1 female bias in S. sitchensis secondary sex
      ratios across all disturbance zones and habitats. Despite female plants sometimes
      allocating more resources (in terms of carbon, nitrogen, and phosphorus) to
      reproduction than males, we found no evidence of sex-biased mortality. The
      establishment rate of S. sitchensis experimental stems did not differ between the
      sexes, indicating that vegetative reproduction was not distorting secondary sex
      ratios.* CONCLUSIONS: We hypothesize that S. sitchensis secondary sex ratios
      depend on either early-acting genetic factors affecting the seed sex ratio or sex
      specific germination or survival rates before maturity, as opposed to factors
      associated with reproduction in adult plants.

PMID- 26290553
TI  - Specificity of induced defenses, growth, and reproduction in lima bean (Phaseolus
      lunatus) in response to multispecies herbivory.
AB  - * PREMISE OF THE STUDY: Following herbivore attack, plants can either reduce
      damage by inducing defenses or mitigate herbivory effects through compensatory
      growth and reproduction. It is increasingly recognized that such induced defenses
      in plants are herbivore-specific, but less is known about the specificity of
      compensatory responses. Damage by multiple herbivores may also lead to
      synergistic effects on induction and plant fitness that differ from those caused
      by a single herbivore species. Although largely unstudied, the order of arrival
      and damage by different herbivore species might also play an important role in
      the impacts of herbivory on plants.* METHODS: We investigated the specificity of
      defense induction (phenolics) and effects on growth (number of stems and leaves)
      and reproduction (number of seeds, seed mass, and germination rate) from feeding
      by two generalist leaf-chewing herbivores (Spodoptera eridania and Diabrotica
      balteata) on Phaseolus lunatus plants and evaluated whether simultaneous attack
      by both herbivores and their order of arrival influenced such dynamics.* KEY
      RESULTS: Herbivory increased levels of leaf phenolics, but such effects were not
      herbivore-specific. In contrast, herbivory enhanced seed germination in an
      herbivore-specific manner. For all variables measured, the combined effects of
      both herbivore species did not differ from their individual effects. Finally, the
      order of herbivore arrival did not influence defense induction, plant growth, or
      seed number but did influence seed mass and germination.* CONCLUSIONS: Overall,
      this study highlights novel aspects of the specificity of plant responses induced
      by damage from multiple species of herbivores and uniquely associates such
      effects with plant lifetime fitness.

PMID- 26290556
TI  - Tripartite mutualism: facilitation or trade-offs between rhizobial and
      mycorrhizal symbionts of legume hosts.
AB  - * PREMISE OF THE STUDY: Multiple mutualist effects (MMEs) are common in nature,
      yet we lack a predictive understanding of how two mutualists on the same host
      will influence each other and whether these effects will be positive or negative.
      Leguminous plants maintain root symbioses with two nutritional mutualists:
      rhizobia that fix atmospheric nitrogen and arbuscular mycorrhizal fungi (AMF)
      that increase phosphorus uptake. Both symbionts receive plant carbon, and host
      genetic networks that regulate colonization are partially shared by both
      symbioses; whether these factors generate trade-offs or facilitation between
      rhizobial and AMF symbionts of legumes is not well known.* METHODS: We evaluated
      host allocation to each symbiont in three settings. First, in situ in a remnant
      prairie, then in a greenhouse experiment with multiple plant populations, and
      finally under manipulated rhizobium densities in the greenhouse.* KEY RESULTS: In
      the remnant prairie, rhizobium nodule number and colonization of AMF were
      positively correlated, and plants with increased nodule number had higher fitness
      in the field, generating indirect selection on the colonization of AMF. In the
      greenhouse experiment, allocation to each symbiont was genetically variable among
      populations, with some suggestion that rhizobium and AMF colonization are
      positively genetically correlated. Finally, increasing the number of rhizobia in
      the soil decreased AMF colonization.* CONCLUSIONS: Our results suggest that trade
      offs between plant colonization by rhizobia and AMF are context dependent and
      might not be common under field conditions, but that physiological and/or genetic
      drivers couple these two symbioses in nature.

PMID- 26290555
TI  - The non-native plant Rosa multiflora expresses shade avoidance traits under low
      light availability.
AB  - * PREMISE OF THE STUDY: Shade tolerance is a key trait promoting invasive plant
      performance in forest interiors. Rosa multiflora is a problematic invasive shrub
      in the northeastern United States, occurring in edge habitats and encroaching
      into forests. Our objective was to evaluate the shade tolerance of R. multiflora
      to assess how ecophysiological traits may facilitate its spread into forest
      interiors.* METHODS: In the field, we documented shrub and seed bank density,
      fecundity, phenology, and seasonal photosynthetic rates of R. multiflora in
      contrasting light environments. In the greenhouse, we exposed seedlings to
      simulated canopy treatments by altering spectral quantity and quality, mimicking
      habitats ranging from open fields to forest interiors.* KEY RESULTS: In the
      field, shrub density and fecundity of R. multiflora sharply increased with light
      availability. However, no differences were observed between forest edge and
      interior seed banks. Rosa multiflora initiated leaf growth earlier and retained
      leaves longer than canopy vegetation and tended to have higher photosynthetic
      rates in spring and fall. In the greenhouse, plants displayed shade-avoidance
      traits, decreasing relative growth rate and reducing branching, while increasing
      elongation and showing no change in light response curve parameters.*
      CONCLUSIONS: In deciduous forest understories, R. multiflora appears to make use
      of a lengthened growing season in spring and fall, and therefore, substantial
      growth and spread through intact forests appears dependent on canopy gaps.
      Management should focus on reducing edge populations to reduce spread into the
      interior and on monitoring newly created canopy gaps.

PMID- 26290557
TI  - Contrasting patterns of genetic diversity across the ranges of Pinus monticola
      and P. strobus: a comparison between eastern and western North American
      postglacial colonization histories.
AB  - * Premises of the study: Understanding the influence of recent glacial and
      postglacial periods on species' distributions is key for predicting the effects
      of future environmental changes. We investigated the influence of two
      physiographic landscapes on population structure and postglacial colonization of
      two white pine species of contrasting habitats: P. monticola, which occurs in the
      highly mountainous region of western North America, and P. strobus, which occurs
      in a much less mountainous area in eastern North America.* METHODS: To
      characterize the patterns of genetic diversity and population structure across
      the ranges of both species, 158 and 153 single nucleotide polymorphism (SNP)
      markers derived from expressed genes were genotyped on range-wide samples of 61
      P. monticola and 133 P. strobus populations, respectively.* KEY RESULTS: In P.
      monticola, a steep latitudinal decrease in genetic diversity likely resulted from
      postglacial colonization involving rare long-distance dispersal (LDD) events. In
      contrast, no geographic patterns of diversity were detected in P. strobus,
      suggesting recolonization via a gradually advancing front or frequent LDD events.
      For each species, structure analyses identified two distinct southern and
      northern genetic groups that likely originated from two different glacial
      lineages. At a finer scale, and for the two species, smaller subgroups were
      detected that could be remnants of cryptic refugia.* CONCLUSION: During
      postglacial colonization, the western and eastern North American landscapes had
      different impacts on genetic signatures in P. monticola compared with P. strobus.
      We discuss the importance of our findings for conservation programs and
      predictions of species' response to climate change.

PMID- 26290558
TI  - Liquidambar maomingensis sp. nov. (Altingiaceae) from the late Eocene of South
      China.
AB  - * PREMISE OF THE STUDY: Phylogenetic analysis of DNA sequence data has changed
      our view on the evolution and systematics of plant taxa. Based on the
      phylogenetic analysis of several molecular markers, fruit anatomy, and pollen
      morphology, the genera Altingia and Semiliquidambar were formally transferred to
      the genus Liquidambar. The new species of Liquidambar from the Eocene of South
      China significantly extends our knowledge of the variability of the morphological
      characters of this genus in the geological past. Fossil leaves in conjunction
      with data on the associated reproductive structures allow us to make inferences
      about patterns in the evolutionary history of Liquidambar.* METHODS: Fossil
      leaves and associated reproductive structures preserved as impressions were
      described and compared with the corresponding organs of extant and fossil
      relatives. The morphological variation of numerous leaves was examined by
      stereomicroscopy.* KEY RESULTS: Liquidambar maomingensis sp. nov. is
      characterized by polymorphic leaves including both palmately lobed and unlobed
      leaves. This study presents the first observations of such dimorphism in the
      fossil record of Liquidambar leaves. Two distinct leaf groups are interpreted as
      sun and shade leaves.* CONCLUSIONS: The fossil leaves and associated
      infructescences from Maoming probably belong to the same plant. The occurrence of
      fossil leaves similar to those of extant species previously considered within
      Semiliquidambar and Liquidambar with the associated infructescences close to
      those of Altingia provide paleobotanical evidence that justifies combining the
      genera Liquidambar, Altingia, and Semiliquidambar into the single genus
      Liquidambar as recently proposed based on molecular markers.

PMID- 26290559
TI  - Variation in life-history traits and their plasticities to elevational
      transplantation among seed families suggests potential for adaptative evolution
      of 15 tropical plant species to climate change.
AB  - * PREMISE OF THE STUDY: Because not all plant species will be able to move in
      response to global warming, adaptive evolution matters largely for plant
      persistence. As prerequisites for adaptive evolution, genetic variation in and
      selection on phenotypic traits are needed, but these aspects have not been
      studied in tropical species. We studied how plants respond to transplantation to
      different elevations on Mt. Kilimanjaro, Tanzania, and whether there is
      quantitative genetic (among-seed family) variation in and selection on life
      history traits and their phenotypic plasticity to the different environments.*
      METHODS: We reciprocally transplanted seed families of 15 common tropical,
      herbaceous species of the montane and savanna vegetation zone at Mt. Kilimanjaro
      to a watered experimental garden in the montane (1450 m) and in the savanna (880
      m) zone at the mountain's slope and measured performance, reproductive, and
      phenological traits.* RESULTS: Plants generally performed worse in the savanna
      garden, indicating that the savanna climate was more stressful and thus that
      plants may suffer from future climate warming. We found significant quantitative
      genetic variation in all measured performance and reproductive traits in both
      gardens and for several measures of phenotypic plasticity in response to
      elevational transplantation. Moreover, we found positive selection on traits at
      low and intermediate trait values levelling to neutral or negative selection at
      high values.* CONCLUSIONS: We conclude that common plants at Mt. Kilimanjaro
      express quantitative genetic variation in fitness-relevant traits and in their
      plasticities, suggesting potential to adapt evolutionarily to future climate
      warming and increased temperature variability.

PMID- 26290560
TI  - Cytotype distribution patterns, ecological differentiation, and genetic structure
      in a diploid-tetraploid contact zone of Cardamine amara.
AB  - * PREMISE OF THE STUDY: Contact zones between diploids and their autopolyploid
      descendants represent a unique evolutionary venue for studying polyploid
      establishment, cytotype coexistence, and interactions. Here, we examine cytotype
      coexistence in a diploid-tetraploid contact zone of a perennial herb, Cardamine
      amara, located north of the Alps by assessing cytotype spatial patterns,
      ecological divergence, and genetic variation and structure.* METHODS: Flow
      cytometry was applied to screen DNA ploidy levels in 302 populations (3296
      individuals) and the genetic variation of a selection of 25 populations was
      examined using microsatellite and AFLP markers. Environmental (landscape and
      climatic) data were analyzed to assess ecological differentiation between the
      cytotypes.* KEY RESULTS: A parapatric distribution of the cytotypes with a
      relatively wide (over 100 km in some regions) secondary contact zone was
      identified. Mixed-ploidy populations, documented for the first time in this
      species, as well as triploid individuals were found along the diploid-tetraploid
      borderline. Different climatic requirements of the two main cytotypes were
      revealed, mirrored in their altitudinal separation. The tetraploids were
      genetically differentiated from both the diploids and the modeled, in silico
      autotetraploid genotypes, in accordance with the assumed polyploid origin and
      spread linked to past glaciations, and largely independent evolution in
      allopatry.* CONCLUSIONS: The observed spatial and genetic patterns likely reflect
      the evolutionary and colonization history of the two cytotypes and have been
      maintained by multiple factors such as ecological divergence, limited gene flow
      between the cytotypes, and the restricted dispersal capacity.

PMID- 26290561
TI  - Spontaneous pneumomediastinum (Hamman's syndrome): a rare cause of postpartum
      chest pain.
AB  - We present a case of a 28-year-old primiparous woman with facial swelling
      followed by acute chest pain immediately after delivery. Chest radiograph
      revealed pneumomediastinum and surgical emphysema. She recovered well within 24 h
      of observation and conservative management. Postpartum spontaneous
      pneumomediastinum should be considered in the differential diagnosis of sudden
      onset postpartum chest pain immediately or a few hours after delivery. It is a
      rare benign condition and usually resolves spontaneously without serious
      consequences. Chest X-ray is the single most important diagnostic test. It is
      important to rule out other serious and life-threatening conditions. Prolonged
      pushing, difficult labour and use of inhalational drugs place young primiparous
      women at higher risk. Recurrence is uncommon in subsequent pregnancy and
      management is unclear, although expectant management with epidural analgaesia to
      prevent recurrence in subsequent pregnancy is suggested. 

PMID- 26290562
TI  - Chronic myeloid leukaemia with extreme thrombocytosis.
AB  - We report two cases of chronic myeloid leukaemia (CML) with extreme
      thrombocytosis. The first patient was a 65-year-old man who presented with
      prolonged history of upper abdominal discomfort, anorexia and two episodes of
      recent gum bleeds without fever or other bleeding manifestations. He was a
      chronic smoker with no other comorbidities. Examination revealed moderate
      hepatosplenomegaly. On investigation, he was found to have extreme thrombocytosis
      (3,500,000/mm(3)) and leucocytosis with moderate anaemia. In view of the
      leucocytosis, he was investigated for CML and found to be positive for BCR-ABL by
      reverse transcription PCR (RT-PCR). He received imatinib 400 mg/day and achieved
      complete haematological response at the end of 3 months. The second patient was a
      7-year-old boy who presented with fever, cough and cold of 2-week duration.
      Examination revealed mild hepatomegaly with palpable spleen tip. Haemogram and
      peripheral smear revealed moderate leucocytosis with extreme thrombocytosis
      (2,800,000/mm(3)). On evaluation, he was found to be BCR-ABL positive and
      responded well to imatinib treatment. In both these cases, massive thrombocytosis
      was an unusual presentation of a well-known entity, namely, CML. This degree of
      thrombocytosis is usually seen only in essential thrombocytosis.

PMID- 26290563
TI  - A rare case of fever of unknown origin: subcutaneous panniculitis-like T-cell
      lymphoma (SPTCL).
AB  - A 26-year-old man presented with high-grade fever, chills, productive cough and
      episodic abdominal pain of 6 months duration. Physical examination revealed that
      the patient was febrile and had multiple, ill-defined, tender, indurated,
      erythematous nodules and plaques over the trunk and thighs. Systemic examination
      and investigations revealed bilateral exudative pleural effusion with an
      increased adenosine deaminase (ADA) level. Pulmonary tuberculosis was suspected
      and the patient was started on a standard four-drug antitubercular regimen. Since
      his fever persisted, biopsy of the plaque over the trunk was performed, which
      showed lobular panniculitis with atypical lymphoid cells. Immunohistochemistry
      showed atypical lymphoid cells, which were CD3 and CD8 positive and CD4 negative.
      Based on the clinical features, skin biopsy and immunohistochemistry, the
      diagnosis of subcutaneous panniculitis-like T-cell lymphoma was made. The patient
      was treated with chemotherapy followed by bone marrow transplantation, and 4-year
      follow-up showed complete remission of lymphoma. 

PMID- 26290564
TI  - Malpositioned IUCD: the menace of postpartum IUCD insertion.
AB  - Use of a postpartum intrauterine contraceptive device (PPIUCD) is a highly
      effective, reversible and long-acting family planning method that can be
      initiated in the immediate postpartum period, especially in lactating women.
      PPIUCDs have been inserted in more than 65,000 women worldwide and the numbers
      are increasing with many countries introducing PPIUCDs as part of their family
      planning programme. As the numbers of PPIUCD insertions are increasing, we are
      getting wiser regarding complications of this procedure. One of the less
      understood entities is a malpositioned PPIUCD, a situation where the IUCD is
      present inside the uterus but its placement is eccentric and a part or the whole
      of it may be embedded in the myometrium. It can present as lost strings or as a
      failure to remove the intrauterine device. We present a series of cases with
      malpositioned PPIUCDs and their management.

PMID- 26290565
TI  - Coverage of denuded labial bone resulting from post space preparation with a free
      gingival autograft: lessons learnt.
AB  - Rehabilitation of endodontically treated teeth by post and core preparation is a
      common procedure in day to day dental practice. However, in some instances, post
      space preparation can produce excessive frictional heat leading to significant
      damage to the attachment apparatus of the tooth as well as to the overlying soft
      tissue. This report describes a case of mucosal dehiscence arising due to trauma
      induced by inadvertent post space preparation. The denuded mucosa was restored to
      its physiological position with the help of free gingival autograft obtained from
      the palatal donor site. The aesthetic results obtained were excellent and have
      been stable for a period of 2 years. 

PMID- 26290566
TI  - Myxoma of the femur: an unusual site of origin.
AB  - Skeletal myxomas are rare benign tumours. Their occurrence in long bones of the
      extremities is rarely reported. A 45-year-old man presented with pain in his left
      proximal thigh for a duration of 4 months. Movements of the hip were painful.
      Radiography revealed an expansile osteolytic lesion in the left proximal femur
      near the lesser trochanteric region. On MRI, the lesion showed a homogenous
      signal enhancement with no cortical disruption. Extended curettage and bone
      grafting was performed. On gross examination, the curetted specimen was a
      yellowish-white mucoid material. Histopathology showed a tumour consisting of
      spindle-shaped and stellate-shaped cells with widely separated myxoid mucoidy
      stroma, suggestive of intraosseous myxoma. At 2 years follow-up, there were no
      signs of recurrence and the patient was doing well with excellent hip and knee
      function.

PMID- 26290567
TI  - Penile epidermal inclusion cyst: a rare location.

PMID- 26290568
TI  - The Growing Burden of Endometrial Cancer: A Major Racial Disparity Affecting
      Black Women.
AB  - BACKGROUND: In contrast with the decreasing incidence seen for most cancers,
      endometrial cancer has been increasing in the United States. We examined whether
      the increasing incidence and mortality from endometrial cancer are equally
      distributed by race/ethnicity and tumor histologic subtype. METHODS:
      Surveillance, Epidemiology, and End Results (SEER) endometrial cancer incidence
      and mortality data were obtained from 2000 to 2011. Age-adjusted incidence and
      incidence-based mortality rates, 95% confidence intervals, and annual percent
      changes (APC) were calculated. Rate ratios were calculated to compare
      racial/ethnic groups. Five-year relative survival rates were presented to explore
      survival by stage at diagnosis. RESULTS: Incidence rates for endometrial cancers
      are rising across all racial/ethnic groups, with the greatest APC seen among non
      Hispanic black (NHB) and Asian women (APC, 2.5 for both). NHB women have
      significantly higher incidence rates of aggressive endometrial cancers (clear
      cell, serous, high-grade endometrioid, and malignant mixed Mullerian tumors)
      compared with non-Hispanic white (NHW) women. Hispanic and Asian women have
      incidence rates equal to or lower than NHW women for all tumor subtypes. For
      nearly every stage and subtype, the 5-year relative survival for NHB women is
      significantly less than NHW women, whereas Hispanic and Asian women have the same
      or better survival. CONCLUSIONS: Endometrial cancer incidence is increasing for
      all women, particularly the aggressive subtypes. The disparity associated with
      excess incidence for these aggressive histologic subtypes and poorer survival is
      limited to NHB women. IMPACT: Increasing rates of aggressive endometrial cancers
      may widen the survival disparity between NHW and NHB women.

PMID- 26290569
TI  - Genomic-Enabled Prediction of Ordinal Data with Bayesian Logistic Ordinal
      Regression.
AB  - Most genomic-enabled prediction models developed so far assume that the response
      variable is continuous and normally distributed. The exception is the probit
      model, developed for ordered categorical phenotypes. In statistical applications,
      because of the easy implementation of the Bayesian probit ordinal regression
      (BPOR) model, Bayesian logistic ordinal regression (BLOR) is implemented rarely
      in the context of genomic-enabled prediction [sample size (n) is much smaller
      than the number of parameters (p)]. For this reason, in this paper we propose a
      BLOR model using the Polya-Gamma data augmentation approach that produces a Gibbs
      sampler with similar full conditional distributions of the BPOR model and with
      the advantage that the BPOR model is a particular case of the BLOR model. We
      evaluated the proposed model by using simulation and two real data sets. Results
      indicate that our BLOR model is a good alternative for analyzing ordinal data in
      the context of genomic-enabled prediction with the probit or logit link.

PMID- 26290571
TI  - A Genomic Selection Index Applied to Simulated and Real Data.
AB  - A genomic selection index (GSI) is a linear combination of genomic estimated
      breeding values that uses genomic markers to predict the net genetic merit and
      select parents from a nonphenotyped testing population. Some authors have
      proposed a GSI; however, they have not used simulated or real data to validate
      the GSI theory and have not explained how to estimate the GSI selection response
      and the GSI expected genetic gain per selection cycle for the unobserved traits
      after the first selection cycle to obtain information about the genetic gains in
      each subsequent selection cycle. In this paper, we develop the theory of a GSI
      and apply it to two simulated and four real data sets with four traits. Also, we
      numerically compare its efficiency with that of the phenotypic selection index
      (PSI) by using the ratio of the GSI response over the PSI response, and the PSI
      and GSI expected genetic gain per selection cycle for observed and unobserved
      traits, respectively. In addition, we used the Technow inequality to compare GSI
      vs. PSI efficiency. Results from the simulated data were confirmed by the real
      data, indicating that GSI was more efficient than PSI per unit of time. 

PMID- 26290570
TI  - SUMO-Enriched Proteome for Drosophila Innate Immune Response.
AB  - Small ubiquitin-like modifier (SUMO) modification modulates the expression of
      defense genes in Drosophila, activated by the Toll/nuclear factor-kappaB and
      immune-deficient/nuclear factor-kappaB signaling networks. We have, however,
      limited understanding of the SUMO-modulated regulation of the immune response and
      lack information on SUMO targets in the immune system. In this study, we measured
      the changes to the SUMO proteome in S2 cells in response to a lipopolysaccharide
      challenge and identified 1619 unique proteins in SUMO-enriched lysates. A
      confident set of 710 proteins represents the immune-induced SUMO proteome and
      analysis suggests that specific protein domains, cellular pathways, and protein
      complexes respond to immune stress. A small subset of the confident set was
      validated by in-bacto SUMOylation and shown to be bona-fide SUMO targets. These
      include components of immune signaling pathways such as Caspar, Jra, Kay, cdc42,
      p38b, 14-3-3epsilon, as well as cellular proteins with diverse functions, many
      being components of protein complexes, such as prosbeta4, Rps10b, SmD3, Tango7,
      and Aats-arg. Caspar, a human FAF1 ortholog that negatively regulates immune
      deficient signaling, is SUMOylated at K551 and responds to treatment with
      lipopolysaccharide in cultured cells. Our study is one of the first to describe
      SUMO proteome for the Drosophila immune response. Our data and analysis provide a
      global framework for the understanding of SUMO modification in the host response
      to pathogens.

PMID- 26290572
TI  - Identification and Correction of Sample Mix-Ups in Expression Genetic Data: A
      Case Study.
AB  - In a mouse intercross with more than 500 animals and genome-wide gene expression
      data on six tissues, we identified a high proportion (18%) of sample mix-ups in
      the genotype data. Local expression quantitative trait loci (eQTL; genetic loci
      influencing gene expression) with extremely large effect were used to form a
      classifier to predict an individual's eQTL genotype based on expression data
      alone. By considering multiple eQTL and their related transcripts, we identified
      numerous individuals whose predicted eQTL genotypes (based on their expression
      data) did not match their observed genotypes, and then went on to identify other
      individuals whose genotypes did match the predicted eQTL genotypes. The
      concordance of predictions across six tissues indicated that the problem was due
      to mix-ups in the genotypes (although we further identified a small number of
      sample mix-ups in each of the six panels of gene expression microarrays).
      Consideration of the plate positions of the DNA samples indicated a number of off
      by-one and off-by-two errors, likely the result of pipetting errors. Such sample
      mix-ups can be a problem in any genetic study, but eQTL data allow us to
      identify, and even correct, such problems. Our methods have been implemented in
      an R package, R/lineup. 

PMID- 26290573
TI  - Three authors reply.

PMID- 26290575
TI  - The King Is Dead, Long Live the King! JBS Special Issue on Screening by RNAi and
      Precise Genome Editing Technologies.

PMID- 26290574
TI  - A Prospective Investigation of the Association Between Urinary Excretion of
      Dietary Lignan Metabolites and Weight Change in US Women.
AB  - Results from animal studies have consistently suggested that lignans play a role
      in the regulation of in body weight, but evidence from human studies has been
      limited. We examined the associations between urinary excretion of enterolactone
      and enterodiol, the major intestinal microbial metabolites of dietary lignans,
      and 10-year prospective weight change using data from 2 well-characterized cohort
      studies of US women: the Nurses' Health Study (2000-2010) and Nurses' Health
      Study II (1997-2007). Urinary excretion levels of enterolactone and enterodiol
      were measured at baseline. Associations with prospective weight change were
      analyzed using a multivariable-adjusted linear mixed-effects model. We observed
      that women in the highest quartile of urinary excretion of total lignans had
      significantly lower baseline body mass indices (weight in kilograms divided by
      height in meters squared) (mean, 24.6, 95% confidence interval (CI): 23.9, 25.2)
      than did those in the lowest quartile (mean, 27.7, 95% CI: 27.0, 28.4; P for
      trend < 0.01). Compared with women in the lowest quartile of enterodiol
      excretion, those in the highest quartile gained 0.27 kg/year less weight (95% CI:
      0.12, 0.41; P for trend < 0.01) during the 10-year follow-up. The association was
      borderline significant for enterolactone (for the fourth vs. first quartile,
      least square mean of weight change rate = -0.14 kg/year, 95% CI: -0.29, 0.00).
      Our data suggest that higher urinary excretion of lignan metabolites, especially
      enterodiol, is associated with modestly slower weight gain. 

PMID- 26290576
TI  - The ability of medial patellofemoral ligament reconstruction to correct patellar
      kinematics and contact mechanics in the presence of a lateralized tibial
      tubercle.
AB  - BACKGROUND: Tibial tubercle (TT) transfer and medial patellofemoral ligament
      (MPFL) reconstruction are used after patellar dislocations. However, there is no
      objective evidence to guide surgical decision making, such as the ability of MPFL
      reconstruction to restore normal behavior in the presence of a lateralized TT.
      HYPOTHESIS: MPFL reconstruction will only restore joint contact mechanics and
      patellar kinematics for TT-trochlear groove (TG) distances up to an identifiable
      limit. STUDY DESIGN: Controlled laboratory study. METHODS: Eight fresh-frozen
      cadaveric knees (mean TT-TG distance, 10.4 mm) were placed on a testing rig.
      Individual quadriceps heads and the iliotibial band were loaded with 205 N in
      physiological directions using a weighted pulley system. Patellofemoral contact
      pressures and patellar tracking were measured at 0 degrees , 10 degrees , 20
      degrees , 30 degrees , 60 degrees , and 90 degrees  of flexion using pressure
      sensitive film and an optical tracking system. The MPFL attachments were marked.
      TT osteotomy was performed, and a metal T-plate was fixed to the anterior tibia
      with holes at 5-mm intervals for TT fixation. The anatomic TT position was
      restored after plate insertion. The TT was lateralized in 5-mm intervals up to 15
      mm, with pressure and tracking measurements recorded. The MPFL was transected and
      all measurements repeated before and after MPFL reconstruction using a double
      stranded gracilis tendon graft. Data were analyzed using repeated-measures ANOVA,
      Bonferroni post hoc analysis, and paired t tests. RESULTS: MPFL transection
      significantly elevated lateral patellar tilt and translation and reduced mean
      medial contact pressures during early knee flexion. These effects increased
      significantly with TT lateralization. MPFL reconstruction restored patellar
      translation and mean medial contact pressures to the intact state when the TT was
      in anatomic or 5-mm lateralized positions. However, these were not restored when
      the TT was lateralized by 10 mm or 15 mm. Patellar tilt was restored after 5-mm
      TT lateralization but not after 10-mm or 15-mm lateralization. CONCLUSION:
      Considering the mean TT-TG distance in this study (10.4 mm), findings suggest
      that in patients with TT-TG distances up to 15 mm, patellofemoral kinematics and
      contact mechanics can be restored with MPFL reconstruction. However, for TT-TG
      distances greater than 15 mm, more aggressive surgery such as TT transfer may be
      indicated. CLINICAL RELEVANCE: This provides guidance to surgeons as to the
      threshold at which MPFL reconstruction may satisfactorily restore patellofemoral
      mechanics, beyond which more invasive surgery such as TT transfer may be
      indicated.

PMID- 26290578
TI  - Water from the rock: Ancient aquatic angiosperms flow from the fossil record.

PMID- 26290577
TI  - Nonmuscle myosin heavy chain IIA mediates Epstein-Barr virus infection of
      nasopharyngeal epithelial cells.
AB  - EBV causes B lymphomas and undifferentiated nasopharyngeal carcinoma (NPC).
      Although the mechanisms by which EBV infects B lymphocytes have been extensively
      studied, investigation of the mechanisms by which EBV infects nasopharyngeal
      epithelial cells (NPECs) has only recently been enabled by the successful growth
      of B lymphoma Mo-MLV insertion region 1 homolog (BMI1)-immortalized NPECs in
      vitro and the discovery that neuropilin 1 expression positively affects EBV
      glycoprotein B (gB)-mediated infection and tyrosine kinase activations in
      enhancing EBV infection of BMI1-immortalized NPECs. We have now found that even
      though EBV infected NPECs grown as a monolayer at extremely low efficiency (<3%),
      close to 30% of NPECs grown as sphere-like cells (SLCs) were infected by EBV. We
      also identified nonmuscle myosin heavy chain IIA (NMHC-IIA) as another NPEC
      protein important for efficient EBV infection. EBV gH/gL specifically interacted
      with NMHC-IIA both in vitro and in vivo. NMHC-IIA densely aggregated on the
      surface of NPEC SLCs and colocalized with EBV. EBV infection of NPEC SLCs was
      significantly reduced by NMHC-IIA siRNA knock-down. NMHC-IIA antisera also
      efficiently blocked EBV infection. These data indicate that NMHC-IIA is an
      important factor for EBV NPEC infection. 

PMID- 26290579
TI  - Defusing redox bombs?

PMID- 26290582
TI  - Collection-limited theory interprets the extraordinary response of single
      semiconductor organic solar cells.
AB  - The bulk heterojunction (BHJ) organic photovoltaic (OPV) architecture has
      dominated the literature due to its ability to be implemented in devices with
      relatively high efficiency values. However, a simpler device architecture based
      on a single organic semiconductor (SS-OPV) offers several advantages: it obviates
      the need to control the highly system-dependent nanoscale BHJ morphology, and
      therefore, would allow the use of broader range of organic semiconductors.
      Unfortunately, the photocurrent in standard SS-OPV devices is typically very low,
      which generally is attributed to inefficient charge separation of the
      photogenerated excitons. Here we show that the short-circuit current density from
      SS-OPV devices can be enhanced significantly (~100-fold) through the use of
      inverted device configurations, relative to a standard OPV device architecture.
      This result suggests that charge generation may not be the performance bottleneck
      in OPV device operation. Instead, poor charge collection, caused by defect
      induced electric field screening, is most likely the primary performance
      bottleneck in regular-geometry SS-OPV cells. We justify this hypothesis by: (i)
      detailed numerical simulations, (ii) electrical characterization experiments of
      functional SS-OPV devices using multiple polymers as active layer materials, and
      (iii) impedance spectroscopy measurements. Furthermore, we show that the
      collection-limited photocurrent theory consistently interprets typical
      characteristics of regular SS-OPV devices. These insights should encourage the
      design and OPV implementation of high-purity, high-mobility polymers, and other
      soft materials that have shown promise in organic field-effect transistor
      applications, but have not performed well in BHJ OPV devices, wherein they adopt
      less-than-ideal nanostructures when blended with electron-accepting materials. 

PMID- 26290580
TI  - Structural characterization of muropeptides from Chlamydia trachomatis
      peptidoglycan by mass spectrometry resolves "chlamydial anomaly".
AB  - The "chlamydial anomaly," first coined by James Moulder, describes the inability
      of researchers to detect or purify peptidoglycan (PG) from pathogenic Chlamydiae
      despite genetic and biochemical evidence and antibiotic susceptibility data that
      suggest its existence. We recently detected PG in Chlamydia trachomatis by a new
      metabolic cell wall labeling method, however efforts to purify PG from pathogenic
      Chlamydiae have remained unsuccessful. Pathogenic chlamydial species are known to
      activate nucleotide-binding oligomerization domain-containing protein 2 (NOD2)
      innate immune receptors by as yet uncharacterized ligands, which are presumed to
      be PG fragments (muramyl di- and tripeptides). We used the NOD2-dependent
      activation of NF-kappaB by C. trachomatis-infected cell lysates as a biomarker
      for the presence of PG fragments within specific lysate fractions. We designed a
      new method of muropeptide isolation consisting of a double filtration step
      coupled with reverse-phase HPLC fractionation of Chlamydia-infected HeLa cell
      lysates. Fractions that displayed NOD2 activity were analyzed by electrospray
      ionization mass spectrometry, confirming the presence of muramyl di- and
      tripeptides in Chlamydia-infected cell lysate fractions. Moreover, the mass
      spectrometry data of large muropeptide fragments provided evidence that
      transpeptidation and transglycosylation reactions occur in pathogenic Chlamydiae.
      These results reveal the composition of chlamydial PG and disprove the
      "glycanless peptidoglycan" hypothesis. 

PMID- 26290581
TI  - E-cadherin junction formation involves an active kinetic nucleation process.
AB  - Epithelial (E)-cadherin-mediated cell-cell junctions play important roles in the
      development and maintenance of tissue structure in multicellular organisms. E
      cadherin adhesion is thus a key element of the cellular microenvironment that
      provides both mechanical and biochemical signaling inputs. Here, we report in
      vitro reconstitution of junction-like structures between native E-cadherin in
      living cells and the extracellular domain of E-cadherin (E-cad-ECD) in a
      supported membrane. Junction formation in this hybrid live cell-supported
      membrane configuration requires both active processes within the living cell and
      a supported membrane with low E-cad-ECD mobility. The hybrid junctions recruit
      alpha-catenin and exhibit remodeled cortical actin. Observations suggest that the
      initial stages of junction formation in this hybrid system depend on the trans
      but not the cis interactions between E-cadherin molecules, and proceed via a
      nucleation process in which protrusion and retraction of filopodia play a key
      role. 

PMID- 26290583
TI  - Color from hierarchy: Diverse optical properties of micron-sized spherical
      colloidal assemblies.
AB  - Materials in nature are characterized by structural order over multiple length
      scales have evolved for maximum performance and multifunctionality, and are often
      produced by self-assembly processes. A striking example of this design principle
      is structural coloration, where interference, diffraction, and absorption effects
      result in vivid colors. Mimicking this emergence of complex effects from simple
      building blocks is a key challenge for man-made materials. Here, we show that a
      simple confined self-assembly process leads to a complex hierarchical geometry
      that displays a variety of optical effects. Colloidal crystallization in an
      emulsion droplet creates micron-sized superstructures, termed photonic balls. The
      curvature imposed by the emulsion droplet leads to frustrated crystallization. We
      observe spherical colloidal crystals with ordered, crystalline layers and a
      disordered core. This geometry produces multiple optical effects. The ordered
      layers give rise to structural color from Bragg diffraction with limited angular
      dependence and unusual transmission due to the curved nature of the individual
      crystals. The disordered core contributes nonresonant scattering that induces a
      macroscopically whitish appearance, which we mitigate by incorporating absorbing
      gold nanoparticles that suppress scattering and macroscopically purify the color.
      With increasing size of the constituent colloidal particles, grating diffraction
      effects dominate, which result from order along the crystal's curved surface and
      induce a vivid polychromatic appearance. The control of multiple optical effects
      induced by the hierarchical morphology in photonic balls paves the way to use
      them as building blocks for complex optical assemblies--potentially as more
      efficient mimics of structural color as it occurs in nature.

PMID- 26290585
TI  - Optimization of HS-GC-FID-MS Method for Residual Solvent Profiling in Active
      Pharmaceutical Ingredients Using DoE.
AB  - Within this research, a headspace (HS) gas chromatography-flame ionization
      detector-mass spectrometry method was developed for profiling of residual
      solvents (RSs) in active pharmaceutical ingredients (APIs). Design of experiment
      was used for optimization of sample preparation, as well as for robustness
      testing of the method. HS equilibration temperature and dilution medium were
      detected as parameters with greater impact on the sensitivity, compared with the
      time used for equilibration of the samples. Regardless of the sample solubility,
      the use of water for sample preparation was found to be crucial for better
      sensitivity. The use of a well-designed strategy for method development and
      robustness testing, additional level of identification confidence, as well as use
      of internal standard provided a strong and reliable analytical tool for API
      fingerprinting, thus enabling the authentication of the substance based on the RS
      profile. 

PMID- 26290584
TI  - Fate of Aneurysmal Common Iliac Artery Landing Zones Used for Endovascular
      Aneurysm Repair.
AB  - PURPOSE: To determine outcomes of aneurysmal common iliac arteries (aCIA) used
      for landing zones (LZs) during endovascular aneurysm repair (EVAR). METHODS: This
      single-center study retrospectively compared 57 EVAR patients (mean age 72+/-8
      years; 56 men) with 70 aCIAs (diameter >=20 mm) to 25 control EVAR subjects (mean
      age 73+/-7 years; 20 men) with 50 normal (<=15-mm) CIA LZs treated consecutively
      during the same time interval. The CIA LZ measurements were analyzed using random
      effects linear mixed models to determine diameter change over time. Life tables
      were used to estimate freedom from endoleak, reintervention, and all-cause
      mortality. RESULTS: The mean maximum preoperative CIA diameter in the aCIA LZ
      group was 24.8+/-4.5 mm (range 20.0-47.3, median 23.9) vs 13.6+/-1.5 mm (range
      9.2-15.0, median 13.9; p<0.001) in the controls. Nineteen aCIA LZs were treated
      outside the instructions for use of the device. Median follow-up in the aCIAs LZ
      cohort was 39.2 months [interquartile range (IQR) 15, 61] vs 49.3 months (IQR 36,
      61) in the controls (p=0.06). The rate of aCIA LZ change (0.09 mm/mo, 95% CI 0.07
      to 0.1) was significantly greater than controls (0.03 mm/mo, 95% CI -0.009 to
      0.07; p<0.0001). No type Ib endoleaks developed in either group; however, aCIA LZ
      patients had 6 (11%) iliac limb-related reinterventions. There were significantly
      more endograft-related reinterventions in the aCIA LZ patients (n=10, 14%)
      compared with controls (n=2, 4%; p=0.06). There was no difference in mortality or
      freedom from any post-hospital discharge endoleak. CONCLUSION: Aneurysmal CIA LZs
      used during EVAR experience greater dilatation compared with normal LZs, but no
      significant difference in outcome was noted in midterm follow-up. However, an
      increased incidence of graft limb complications or endograft-related
      reintervention may be encountered. Use of aCIA LZs appears to be safe; however,
      greater patient numbers and longer follow-up are needed to understand the
      clinical implications of morphologic changes in these vessels when used during
      EVAR.

PMID- 26290586
TI  - Prescriptive Oriented Drug Analysis of Multiple Sclerosis Disease by LC-UV in
      Whole Human Blood.
AB  - As a polytherapy treatment, multiple sclerosis disease demands prescriptions with
      more than one drug. Polytherapy is sometimes rational for drug combinations
      chosen to minimize adverse effects. Estimation of drugs that are concomitantly
      administered in polytherapy is acceptable as it shortens the analytical
      timepoints and also the usage of biological matrices. In clinical phase trials,
      the withdrawal of biofluids is a critical issue for each analysis. Estimating all
      the coadminsitered drugs in a single shot will be more effective and economical
      for pharmaceuticals. A single, simple, rapid and sensitive high-performance
      liquid chromatography assay method has been developed with UV detection and fully
      validated for the quantification of 14 drugs (at random combinations) used in the
      treatment of multiple sclerosis disease. The set of combinations was based on
      prescriptions to patients. Separations were achieved on an X-Terra MS C18 (100 *
      3.9 mm, 5 um) column. The analytes were extracted from 50 uL aliquots of whole
      human blood with protein precipitation using acetonitrile. All the drugs were
      sufficiently stable during storage for 24 h at room temperature and for 23 days
      at 2-8 degrees C. The percentage recoveries of all drugs were between 90 and
      115%, with RSD values <10.6%. This method has been shown to be reproducible and
      sensitive and can be applied to clinical samples from pharmacokinetic studies and
      also a useful tool in studying the drug interaction studies. 

PMID- 26290587
TI  - A patient-initiated DMARD self-monitoring service for people with rheumatoid or
      psoriatic arthritis on methotrexate: a randomised controlled trial.
AB  - OBJECTIVE: To determine the effectiveness of a patient-initiated disease
      modifying antirheumatic drugs (DMARD) self-monitoring service for people with
      rheumatoid (RA) or psoriatic arthritis (PsA) on methotrexate. METHODS: A two-arm,
      single-centre, randomised controlled trial assessing superiority in relation to
      healthcare use, clinical and psychosocial outcomes. Participants were 100 adults
      with either RA or PsA on a stable dose of methotrexate, randomly assigned to
      usual care or the patient-initiated service. Intervention participants were
      trained how to understand and interpret their blood tests and use this
      information to initiate care from their clinical nurse specialist (CNS). The
      primary outcome was the number of outpatient visits to the CNS during the trial
      period. Differences between groups were analysed using Poisson regression models.
      Secondary outcomes were collected at baseline and after the third and sixth blood
      tests. Disease activity was measured using either the Disease Activity Score in
      28 joints or Psoriatic Arthritis Response Criteria (PsARC), pain and fatigue
      using a visual numeric scale and the Health Assessment Question-II, Hospital
      Anxiety and Depression Scale and SF12 were completed to assess disability, mood
      and quality of life, respectively. Differences between groups over time on
      secondary outcomes were analysed using multilevel models. RESULTS: The patient
      initiated DMARD self-monitoring service was associated with 54.55% fewer visits
      to the CNS (p<0.0001), 6.80% fewer visits to the rheumatologist (p=0.23) and
      38.80% fewer visits to the general practitioner (p=0.07), compared with control
      participants. There was no association between trial arm and any of the clinical
      or psychosocial outcomes. CONCLUSIONS: The results suggest that a patient
      initiated service that incorporates patients' self-monitoring DMARD therapy can
      lead to significant reductions in healthcare use, while maintaining clinical and
      psychosocial well-being. TRIAL REGISTRATION NUMBER: ISRCTN21613721.

PMID- 26290589
TI  - Acute serum amyloid A is an endogenous TLR2 ligand that mediates inflammatory and
      angiogenic mechanisms.
AB  - INTRODUCTION: Acute-phase serum amyloid A (A-SAA) has cytokine-like properties
      and is expressed at sites of inflammation. We examined whether A-SAA-induced pro
      inflammatory mechanisms are mediated through Toll-like receptor 2 (TLR2) in
      rheumatoid arthritis (RA). METHODS: The effect of A-SAA on human embryonic kidney
      (HEK), TLR2 or TLR4 cells was quantified by nuclear factor (NF)-kappaB luciferase
      reporter assays. A-SAA-induced RASFC and dHMVEC function were performed in the
      presence of a specific neutralising anti-TLR2 mAb (OPN301) (1 MUg/mL) and matched
      IgG isotype control Ab (1 MUg/mL). Cell surface expression of intracellular
      adhesion molecule (ICAM)-1, chemokine expression, cell migration, invasion and
      angiogenesis were assessed by flow cytometry, ELISA, Matrigel invasion chambers
      and tube formation assays. MyD88 expression was assessed by real-time PCR and
      western blot. RESULTS: A-SAA induced TLR2 activation through induction of NF
      kappaB (p<0.05), but failed to induce NF-kappaB in HEK-TLR4 cells, confirming
      specificity for TLR2. A-SAA-induced proliferation, invasion and migration were
      significantly inhibited in the presence of anti-TLR2 (all p<0.05), with no
      significant effect observed for tumour necrosis factor-alpha-induced events.
      Additionally, A-SAA-induced ICAM-1, interleukin-8, monocyte chemoattractant
      protein-1, RANTES and GRO-alpha expression were significantly reduced in the
      presence of anti-TLR2 (all p<0.05), as was A-SAA induced angiogenesis (p<0.05).
      Finally, A-SAA induced MyD88 signalling in RASFC and dHMVEC (p<0.05).
      CONCLUSIONS: A-SAA is an endogenous ligand for TLR2, inducing pro-inflammatory
      effects in RA. Blocking the A-SAA/TLR2 interaction may be a potential therapeutic
      intervention in RA.

PMID- 26290590
TI  - The effect of discontinuous gas exchange on respiratory water loss in
      grasshoppers (Orthoptera: Acrididae) varies across an aridity gradient.
AB  - The significance of discontinuous gas-exchange cycles (DGC) in reducing
      respiratory water loss (RWL) in insects is contentious. Results from single
      species studies are equivocal in their support of the classic 'hygric hypothesis'
      for the evolution of DGC, whereas comparative analyses generally support a link
      between DGC and water balance. In this study, we investigated DGC prevalence and
      characteristics and RWL in three grasshopper species (Acrididae, subfamily
      Pamphaginae) across an aridity gradient in Israel. In order to determine whether
      DGC contributes to a reduction in RWL, we compared the DGC characteristics and
      RWL associated with CO2 release (transpiration ratio, i.e. the molar ratio of RWL
      to CO2 emission rates) among these species. Transpiration ratios of DGC and
      continuous breathers were also compared intraspecifically. Our data show that DGC
      characteristics, DGC prevalence and the transpiration ratios correlate well with
      habitat aridity. The xeric-adapted Tmethis pulchripennis exhibited a
      significantly shorter burst period and lower transpiration ratio compared with
      the other two mesic species, Ocneropsis bethlemita and Ocneropsis lividipes.
      However, DGC resulted in significant water savings compared with continuous
      exchange in T. pulchripennis only. These unique DGC characteristics for T.
      pulchripennis were correlated with its significantly higher mass-specific
      tracheal volume. Our data suggest that the origin of DGC may not be adaptive, but
      rather that evolved modulation of cycle characteristics confers a fitness
      advantage under stressful conditions. This modulation may result from
      morphological and/or physiological modifications.

PMID- 26290591
TI  - Probability distributions of whisker-surface contact: quantifying elements of the
      rat vibrissotactile natural scene.
AB  - Analysis of natural scene statistics has been a powerful approach for
      understanding neural coding in the auditory and visual systems. In the field of
      somatosensation, it has been more challenging to quantify the natural tactile
      scene, in part because somatosensory signals are so tightly linked to the
      animal's movements. The present work takes a step towards quantifying the natural
      tactile scene for the rat vibrissal system by simulating rat whisking motions to
      systematically investigate the probabilities of whisker-object contact in
      naturalistic environments. The simulations permit an exhaustive search through
      the complete space of possible contact patterns, thereby allowing for the
      characterization of the patterns that would most likely occur during long
      sequences of natural exploratory behavior. We specifically quantified the
      probabilities of 'concomitant contact', that is, given that a particular whisker
      makes contact with a surface during a whisk, what is the probability that each of
      the other whiskers will also make contact with the surface during that whisk?
      Probabilities of concomitant contact were quantified in simulations that assumed
      increasingly naturalistic conditions: first, the space of all possible head
      poses; second, the space of behaviorally preferred head poses as measured
      experimentally; and third, common head poses in environments such as cages and
      burrows. As environments became more naturalistic, the probability distributions
      shifted from exhibiting a 'row-wise' structure to a more diagonal structure.
      Results also reveal that the rat appears to use motor strategies (e.g. head
      pitches) that generate contact patterns that are particularly well suited to
      extract information in the presence of uncertainty. 

PMID- 26290592
TI  - Diurnality as an energy-saving strategy: energetic consequences of temporal niche
      switching in small mammals.
AB  - Endogenous daily (circadian) rhythms allow organisms to anticipate daily changes
      in the environment. Most mammals are specialized to be active during the night
      (nocturnal) or day (diurnal). However, typically nocturnal mammals become diurnal
      when energetically challenged by cold or hunger. The circadian thermo-energetics
      (CTE) hypothesis predicts that diurnal activity patterns reduce daily energy
      expenditure (DEE) compared with nocturnal activity patterns. Here, we tested the
      CTE hypothesis by quantifying the energetic consequences of relevant
      environmental factors in mice. Under natural conditions, diurnality reduces DEE
      by 6-10% in energetically challenged mice. Combined with night-time torpor, as
      observed in mice under prolonged food scarcity, DEE can be reduced by ~20%. The
      dominant factor determining the energetic benefit of diurnality is thermal
      buffering provided by a sheltered resting location. Compared with nocturnal
      animals, diurnal animals encounter higher ambient temperatures during both day
      and night, leading to reduced thermogenesis costs in temperate climates. Analysis
      of weather station data shows that diurnality is energetically beneficial on
      almost all days of the year in a temperate climate region. Furthermore,
      diurnality provides energetic benefits at all investigated geographical locations
      on European longitudinal and latitudinal transects. The reduction of DEE by
      diurnality provides an ultimate explanation for temporal niche switching observed
      in typically nocturnal small mammals under energetically challenging conditions.
      Diurnality allows mammals to compensate for reductions in food availability and
      temperature as it reduces energetic needs. The optimal circadian organization of
      an animal ultimately depends on the balance between energetic consequences and
      other fitness consequences of the selected temporal niche.

PMID- 26290588
TI  - Agrin mediates chondrocyte homeostasis and requires both LRP4 and alpha
      dystroglycan to enhance cartilage formation in vitro and in vivo.
AB  - OBJECTIVES: Osteoarthritis (OA) is a leading cause of disability for which there
      is no cure. The identification of molecules supporting cartilage homeostasis and
      regeneration is therefore a major pursuit in musculoskeletal medicine. Agrin is a
      heparan sulfate proteoglycan which, through binding to low-density lipoprotein
      receptor-related protein 4 (LRP4), is required for neuromuscular synapse
      formation. In other tissues, it connects the cytoskeleton to the basement
      membrane through binding to alpha-dystroglycan. Prompted by an unexpected
      expression pattern, we investigated the role and receptor usage of agrin in
      cartilage. METHODS: Agrin expression pattern was investigated in human
      osteoarthritic cartilage and following destabilisation of the medial meniscus in
      mice. Extracellular matrix (ECM) formation and chondrocyte differentiation was
      studied in gain and loss of function experiments in vitro in three-dimensional
      cultures and gain of function in vivo, using an ectopic cartilage formation assay
      in nude mice. Receptor usage was investigated by disrupting LRP4 and alpha
      dystroglycan by siRNA and blocking antibodies respectively. RESULTS: Agrin was
      detected in normal cartilage but was progressively lost in OA. In vitro, agrin
      knockdown resulted in reduced glycosaminoglycan content, downregulation of the
      cartilage transcription factor SOX9 and other cartilage-specific ECM molecules.
      Conversely, exogenous agrin supported cartilage differentiation in vitro and
      ectopic cartilage formation in vivo. In the context of cartilage differentiation,
      agrin used an unusual receptor repertoire requiring both LRP4 and alpha
      dystroglycan. CONCLUSIONS: We have discovered that agrin strongly promotes
      chondrocyte differentiation and cartilage formation in vivo. Our results identify
      agrin as a novel potent anabolic growth factor with strong therapeutic potential
      in cartilage regeneration.

PMID- 26290593
TI  - Nitrogen solubility in odontocete blubber and mandibular fats in relation to
      lipid composition.
AB  - Understanding toothed whale (odontocete) diving gas dynamics is important given
      the recent atypical mass strandings of odontocetes (particularly beaked whales)
      associated with mid-frequency naval sonar. Some stranded whales have exhibited
      gas emboli (pathologies resembling decompression sickness) in their specialized
      intramandibular and extramandibular fat bodies used for echolocation and hearing.
      These tissues have phylogenetically unique, endogenous lipid profiles with poorly
      understood biochemical properties. Current diving gas dynamics models assume an
      Ostwald nitrogen (N2) solubility of 0.07 ml N2 ml(-1) oil in odontocete fats,
      although solubility in blubber from many odontocetes exceeds this value. The
      present study examined N2 solubility in the blubber and mandibular fats of seven
      species across five families, relating it to lipid composition. Across all
      species, N2 solubility increased with wax ester content and was generally higher
      in mandibular fats (0.083 +/- 0.002 ml N2 ml(-1) oil) than in blubber (0.069 +/-
      0.007 ml N2 ml(-1) oil). This effect was more pronounced in mandibular fats with
      higher concentrations of shorter, branched fatty acids/alcohols. Mandibular fats
      of short-finned pilot whales, Atlantic spotted dolphins and Mesoplodon beaked
      whales had the highest N2 solubility values (0.097 +/- 0.005, 0.081 +/- 0.007 and
      0.080 +/- 0.003 ml N2 ml(-1) oil, respectively). Pilot and beaked whales may
      experience high N2 loads during their relatively deeper dives, although more
      information is needed about in vivo blood circulation to mandibular fats. Future
      diving models should incorporate empirically measured N2 solubility of odontocete
      mandibular fats to better understand N2 dynamics and potential pathologies from
      gas/fat embolism.

PMID- 26290594
TI  - Neo-Darwinism is just fine.

PMID- 26290595
TI  - Central tenets of neo-Darwinism broken. Response to 'Neo-Darwinism is just fine'.

PMID- 26290596
TI  - Visual acuity trade-offs and microhabitat-driven adaptation of searching
      behaviour in psyllids (Hemiptera: Psylloidea: Aphalaridae).

PMID- 26290597
TI  - Patatin-related phospholipase A, pPLAIIIalpha, modulates the longitudinal growth
      of vegetative tissues and seeds in rice.
AB  - Patatin-related phospholipase A (pPLA) hydrolyses glycerolipids to produce fatty
      acids and lysoglycerolipids. The Oryza sativa genome has 21 putative pPLAs that
      are grouped into five subfamilies. Overexpression of OspPLAIIIalpha resulted in a
      dwarf phenotype with decreased length of rice stems, roots, leaves, seeds,
      panicles, and seeds, whereas OspPLAIIIalpha-knockout plants had longer panicles
      and seeds. OspPLAIIIalpha-overexpressing plants were less sensitive than wild
      type and knockout plants to gibberellin-promoted seedling elongation.
      OspPLAIIIalpha overexpression and knockout had an opposite effect on the
      expression of the growth repressor SLENDER1 in the gibberellin signalling
      process. OspPLAIIIalpha-overexpressing plants had decreased mechanical strength
      and cellulose content, but exhibited increases in the expression of several
      cellulose synthase genes. These results indicate that OspPLAIIIalpha plays a role
      in rice vegetative and reproductive growth and that the constitutive, high
      activity of OspPLAIIIalpha suppresses cell elongation. The decreased gibberellin
      response in overexpressing plants is probably a result of the decreased ability
      to make cellulose for anisotropic cell expansion. 

PMID- 26290602
TI  - Sulfiredoxin Promotes Colorectal Cancer Cell Invasion and Metastasis through a
      Novel Mechanism of Enhancing EGFR Signaling.
AB  - Sulfiredoxin (SRXN1/Srx) is a multifunction enzyme with a primary antioxidant
      role of reducing the overoxidized inactive form of peroxiredoxins (Prxs). The
      function and mechanisms of Srx in cancer development are not well understood.
      Here, Srx is preferentially expressed in human colorectal cancer cells but not in
      normal colon epithelial cells. Loss-of-function studies demonstrate that
      knockdown of Srx in poorly differentiated colorectal cancer cells not only leads
      to the inhibition of colony formation and cell invasion in vitro, but also
      reduces tumor xenograft growth and represses metastasis to distal organs in a
      mouse orthotopic implantation model. Notably, exactly opposite effects were
      observed in gain-of-function experiments when Srx was ectopically expressed in
      well-differentiated colorectal cancer cells. Mechanistically, expression of Srx
      enhances the activation of MAPK signaling through increasing the C-terminal
      tyrosine phosphorylation levels of EGFR. This function of Srx is mediated through
      its inhibition of EGFR acetylation at K1037, a novel posttranslational
      modification of EGFR in human colorectal cancer cells identified by liquid
      chromatography-electrospray ionization-tandem mass spectrometry (LC/ESI/MS-MS)
      proteomic analysis. Furthermore, abolishment of K1037 acetylation in human
      colorectal cancer cells by site-specific mutagenesis leads to sustained
      activation of EGFR-MAPK signaling. Combined, these data reveal that Srx promotes
      colorectal cancer cell invasion and metastasis through a novel mechanism of
      enhancing EGFR signaling. IMPLICATIONS: Sulfiredoxin is a critical oncogenic
      protein that can be used as a molecular target to develop therapeutics for
      patients with metastatic colorectal cancer.

PMID- 26290603
TI  - Low Levels of IgM Antibodies against an Advanced Glycation Endproduct-Modified
      Apolipoprotein B100 Peptide Predict Cardiovascular Events in Nondiabetic
      Subjects.
AB  - Increased glucose levels are associated with the generation of advanced glycation
      endproduct (AGE) modifications. Interaction between AGE-modified plaque
      components and immune cells is believed to have an important role in the
      development of vascular complications in diabetes. Methylglyoxal (MGO) is one
      type of reactive aldehyde that gives rise to AGE modification. The present study
      analyzed whether autoantibodies against MGO-modified epitopes of the low-density
      lipoprotein apolipoprotein B (apoB) 100 predict cardiovascular events. A library
      consisting of 302 peptides comprising the complete apoB100 molecule was screened
      to identify peptides targeted by MGO-specific autoantibodies. Peptide (p) 220
      (apoB amino acids 3286-3305) was identified as a major target. Baseline IgM and
      IgG against MGO-peptide 220 (p220) were measured in 700 individuals from the
      Malmo Diet and Cancer Cohort. A total of 139 cardiovascular events were
      registered during the 15-y follow-up period. Controlling for major cardiovascular
      risk factors demonstrated that subjects in the lowest tertile of MGO-p220 IgM had
      an increased risk for cardiovascular events (hazard ratio [95% confidence
      interval]: 2.07 [1.22-3.50]; p(trend) = 0.004). Interestingly, the association
      between MGO-p220 IgM and cardiovascular events remained and even tended to become
      stronger when subjects with prevalent diabetes were excluded from the analysis
      (2.51 [1.37-4.61]; p(trend) = 0.002). MGO-p220 IgM was inversely associated with
      blood glucose, but not with oxidized low-density lipoprotein. Finally, we
      demonstrate that anti-MGO-p220 IgM is produced by B1 cells. These data show that
      subjects with low levels of IgM recognizing MGO-modified p220 in apoB have an
      increased risk to develop cardiovascular events and that this association is
      present in nondiabetic subjects.

PMID- 26290605
TI  - Soluble Collectin-12 (CL-12) Is a Pattern Recognition Molecule Initiating
      Complement Activation via the Alternative Pathway.
AB  - Soluble defense collagens including the collectins play important roles in innate
      immunity. Recently, a new member of the collectin family named collectin-12 (CL
      12 or CL-P1) has been identified. CL-12 is highly expressed in umbilical cord
      vascular endothelial cells as a transmembrane receptor and may recognize certain
      bacteria and fungi, leading to opsonophagocytosis. However, based on its
      structural and functional similarities with soluble collectins, we hypothesized
      the existence of a fluid-phase analog of CL-12 released from cells, which may
      function as a soluble pattern-recognition molecule. Using recombinant CL-12 full
      length or CL-12 extracellular domain, we determined the occurrence of soluble CL
      12 shed from in vitro cultured cells. Western blot showed that soluble
      recombinant CL-12 migrated with a band corresponding to ~ 120 kDa under reducing
      conditions, whereas under nonreducing conditions it presented multimeric assembly
      forms. Immunoprecipitation and Western blot analysis of human umbilical cord
      plasma enabled identification of a natural soluble form of CL-12 having an
      electrophoretic mobility pattern close to that of shed soluble recombinant CL-12.
      Soluble CL-12 could recognize Aspergillus fumigatus partially through the
      carbohydrate-recognition domain in a Ca(2+)-independent manner. This led to
      activation of the alternative pathway of complement exclusively via association
      with properdin on A. fumigatus as validated by detection of C3b deposition and
      formation of the terminal complement complex. These results demonstrate the
      existence of CL-12 in a soluble form and indicate a novel mechanism by which the
      alternative pathway of complement may be triggered directly by a soluble pattern
      recognition molecule.

PMID- 26290604
TI  - Lymphocytic Choriomeningitis Virus Expands a Population of NKG2D+CD8+ T Cells
      That Exacerbates Disease in Mice Coinfected with Leishmania major.
AB  - Leishmaniasis is a significant neglected tropical disease that is associated with
      a wide range of clinical presentations and a lifelong persistent infection.
      Because of the chronic nature of the disease, there is a high risk for
      coinfection occurring in patients, and how coinfections influence the outcome of
      leishmaniasis is poorly understood. To address this issue, we infected mice with
      Leishmania major and 2 wk later with lymphocytic choriomeningitis virus (LCMV)
      and then monitored the course of infection. Leishmania parasites are controlled
      by production of IFN-gamma, which leads to macrophage-mediated parasite killing.
      Thus, one might predict that coinfection with LCMV, which induces a strong
      systemic type 1 response, would accelerate disease resolution. However, we found
      that infection with LCMV led to significantly enhanced disease in L. major
      infected animals. This increased disease correlated with an infiltration into the
      leishmanial lesions of NKG2D(+) CD8(+) T cells producing granzyme B, but
      surprisingly little IFN-gamma. We found that depletion of CD8 T cells after viral
      clearance, as well as blockade of NKG2D, reversed the increased pathology seen in
      coinfected mice. Thus, this work highlights the impact a secondary infection can
      have on leishmaniasis and demonstrates that even pathogens known to promote a
      type 1 response may exacerbate leishmanial infections. 

PMID- 26290606
TI  - Critical Cysteine Residues in Both the Calcium-Sensing Receptor and the
      Allosteric Activator AMG 416 Underlie the Mechanism of Action.
AB  - AMG 416 is a novel D-amino acid-containing peptide agonist of the calcium-sensing
      receptor (CaSR) that is being evaluated for the treatment of secondary
      hyperparathyroidism in chronic kidney disease patients receiving hemodialysis.
      The principal amino acid residues and their location in the CaSR that accommodate
      AMG 416 binding and mode of action have not previously been reported. Herein we
      establish the importance of a pair of cysteine residues, one from AMG 416 and the
      other from the CaSR at position 482 (Cys482), and correlate the degree of
      disulfide bond formation between these residues with the pharmacological activity
      of AMG 416. KP-2067, a form of the CaSR agonist peptide, was included to
      establish the role of cysteine in vivo and in disulfide exchange. Studies
      conducted with AMG 416 in pigs showed a complete lack of pharmacodynamic effect
      and provided a foundation for determining the peptide agonist interaction site
      within the human CaSR. Inactivity of AMG 416 on the pig CaSR resulted from a
      naturally occurring mutation encoding tyrosine for cysteine (Cys) at position 482
      in the pig CaSR. Replacing Cys482 in the human CaSR with serine or tyrosine
      ablated AMG 416 activity. Decidedly, a single substitution of cysteine for
      tyrosine at position 482 in the native pig CaSR provided a complete gain of
      activity by the peptide agonist. Direct evidence for this disulfide bond
      formation between the peptide and receptor was demonstrated using a mass
      spectrometry assay. The extent of disulfide bond formation was found to correlate
      with the extent of receptor activation. Notwithstanding the covalent basis of
      this disulfide bond, the observed in vivo pharmacology of AMG 416 showed readily
      reversible pharmacodynamics. 

PMID- 26290607
TI  - Defending the Use of Sulfadoxine-Pyrimethamine for Intermittent Preventive
      Treatment for Malaria in Pregnancy: A Short-Sighted Strategy.

PMID- 26290608
TI  - Uropathogenic Escherichia coli Express Type 1 Fimbriae Only in Surface Adherent
      Populations Under Physiological Growth Conditions.
AB  - BACKGROUND: Most uropathogenic Escherichia coli (UPEC) strains harbor genes
      encoding adhesive type 1 fimbria (T1F). T1F is a key factor for successful
      establishment of urinary tract infection. However, UPEC strains typically do not
      express T1F in the bladder urine, and little is understood about its induction in
      vivo. METHODS: A flow chamber infection model was used to grow UPEC under
      conditions simulating distinct infection niches in the bladder. Type 1
      fimbriation on isolated UPEC was subsequently determined by yeast cell
      agglutination and immunofluorescence microscopy, and the results were correlated
      with the ability to adhere to and invade cultured human bladder cells. RESULTS:
      Although inactive during planktonic growth in urine, T1F expression occurs when
      UPEC settles on and infects bladder epithelial cells or colonizes catheters. As a
      result, UPEC in these sessile populations enhances bladder cell adhesion and
      invasion potential. Only T1F-negative UPEC are subsequently released to the
      urine, thus limiting T1F expression to surface-associated UPEC alone.
      CONCLUSIONS: Our results demonstrate that T1F expression is strictly regulated
      under physiological growth conditions with increased expression during surface
      growth adaptation and infection of uroepithelial cells. This leads to separation
      of UPEC into low-expression planktonic populations and high-expression sessile
      populations.

PMID- 26290609
TI  - Reply to Harrington et al.

PMID- 26290610
TI  - Metabolic profiling in human exposome studies.
AB  - The human metabolome-the complement of small molecule metabolites present in
      biofluids and tissues-represents a significant part of the internal chemical
      milieu and is therefore an important aspect of the human exposome. Metabolic
      profiling approaches, commonly referred to as metabonomics or metabolomics,
      permit detailed and efficient characterisation of human biospecimens; application
      to population studies holds great promise for uncovering new associations and
      causal relationships between environmental factors and chronic disease. In
      addition to the insight metabolic information can provide, metabolic phenotypes
      anchor other molecular readouts and help formulate a systems-level interpretation
      of biological phenomena. In this commentary, we discuss the general approach for
      applying metabolic profiling in exposome studies, alongside recent exemplars. We
      also comment on the complexity and dynamism of the metabolome and highlight both
      the limitations such properties impart and the requirements for dealing with such
      issues in real-world phenotyping studies. Given that several large-scale exposome
      studies are now underway, we offer a perspective on current and future challenges
      that will need to be addressed to maximise their utility in environmental health
      research. 

PMID- 26290612
TI  - Towards evidence based medicine for paediatricians.

PMID- 26290611
TI  - Ligand binding to the ACBD6 protein regulates the acyl-CoA transferase reactions
      in membranes.
AB  - The binding determinants of the human acyl-CoA binding domain-containing protein
      (ACBD) 6 and its function in lipid renewal of membranes were investigated. ACBD6
      binds acyl-CoAs of a chain length of 6 to 20 carbons. The stoichiometry of the
      association could not be fitted to a 1-to-1 model. Saturation of ACBD6 by C16:0
      CoA required higher concentration than less abundant acyl-CoAs. In contrast to
      ACBD1 and ACBD3, ligand binding did not result in the dimerization of ACBD6. The
      presence of fatty acids affected the binding of C18:1-CoA to ACBD6, dependent on
      the length, the degree of unsaturation, and the stereoisomeric conformation of
      their aliphatic chain. ACBD1 and ACBD6 negatively affected the formation of
      phosphatidylcholine (PC) and phosphatidylethanolamine in the red blood cell
      membrane. The acylation rate of lysophosphatidylcholine into PC catalyzed by the
      red cell lysophosphatidylcholine-acyltransferase 1 protein was limited by the
      transfer of the acyl-CoA substrate from ACBD6 to the acyltransferase enzyme.
      These findings provide evidence that the binding properties of ACBD6 are adapted
      to prevent its constant saturation by the very abundant C16:0-CoA and protect
      membrane systems from the detergent nature of free acyl-CoAs by controlling their
      release to acyl-CoA-utilizing enzymes. 

PMID- 26290614
TI  - Application of fatigue management systems: small mines and low technology
      solutions.
AB  - The impact of fatigue is seen not only in its effect on job performance of haul
      truck operators but also on the health of the operator and the productivity at
      the mine site. Its impact can even extend outside of the mine site to the health
      and well-being of the surrounding community (Fourie et al., 2010). In this paper,
      a case study of a small surface mining organization is presented. The goal is to
      highlight the fatigue risk management system implemented at the studied mine
      site. Mine safety personnel who were interviewed discuss the changes made to the
      infrastructure of the mine, to administrative areas such as the number of shifts
      and the use of vacation time, as well as the implementation of new technology
      into haulage vehicles. This paper reviews how these changes are supported in the
      research literature.

PMID- 26290615
TI  - Mental imagery during daily life: Psychometric evaluation of the Spontaneous Use
      of Imagery Scale (SUIS).
AB  - The Spontaneous Use of Imagery Scale (SUIS) is used to measure the tendency to
      use visual mental imagery in daily life. Its psychometric properties were
      evaluated in three independent samples (total N = 1297). We evaluated the
      internal consistency and test-retest reliability of the questionnaire. We also
      examined the structure of the items using exploratory and confirmatory factor
      analysis. Moreover, correlations with other imagery questionnaires provided
      evidence about convergent validity. The SUIS had acceptable reliability and
      convergent validity. Exploratory and confirmatory factor analysis revealed that a
      unidimensional structure fit the data, suggesting that the SUIS indeed measures a
      general use of mental imagery in daily life. Future research can further
      investigate and improve the psychometric properties of the SUIS. Moreover, the
      SUIS could be useful to determine how imagery relates to e.g. psychopathology.

PMID- 26290616
TI  - Molecular Depth Profiling.

PMID- 26290617
TI  - A new class of generalized log rank tests for interval-censored failure time
      data.
AB  - This paper discusses nonparametric comparison of survival functions when one
      observes only interval-censored failure time data (Peto and Peto, 1972; Sun,
      2006; Zhao et al., 2008). For the problem, a few procedures have been proposed in
      the literature. However, most of the existing test procedures determine the test
      results or p-values based on ad hoc methods or the permutation approach.
      Furthermore for the test procedures whose asymptotic distributions have been
      derived, the results are only for the null hypothesis. In other words, no
      nonparametric test procedure exists that has a known asymptotic distribution
      under the alternative hypothesis and thus can be employed to carry out the power
      and test size calculation. In this paper, a new class of generalized log-rank
      tests is proposed and their asymptotic distributions are derived under both null
      and alternative hypotheses. A simulation study is conducted to assess their
      performance for finite sample situations and an illustrative example is provided.

PMID- 26290618
TI  - Images and Meaning-Making in a World of Resemblance: The Bavarian-Saxon Kidney
      Stone Affair of 1580.
AB  - This article de-constructs and re-constructs the dynamic of a sixteenth-century
      political dispute between the Catholic Bavarian Duke Wilhelm V and the Protestant
      Saxon Elector August I. By focusing on the visual imagery which ignited the
      dispute, the paper explores sixteenth-century 'ways of seeing' and the epistemic
      role realistic images played in the production of knowledge about the natural
      world. While the peculiar dynamic of the affair is based on a specific
      understanding of the evidential role of images, the paper also argues that the
      wider socio-cultural context, in particular certain strategies of truth-telling,
      provide further clues as to the dynamic and closure of the affair.

PMID- 26290619
TI  - A comparison of clinical laboratory data for assigning a consensus value for
      manganese in a caprine blood reference material.
AB  - Biomonitoring for manganese (Mn) exposure is important due to its potential to
      cause adverse health effects. In this study, we investigate how different sample
      preparation methods (simple dilution, digestion, volumetric, gravimetric),
      calibration protocols (aqueous, blood-based, standard additions), and
      instrumental techniques affect Mn method bias and analytical imprecision. The
      techniques used included graphite furnace atomic absorption spectrometry (GFAAS),
      dynamic reaction cell inductively coupled plasma mass spectrometry (DRC-ICP-MS),
      and sector field (SF-) ICP-MS. We analyzed NIST SRM 1643e Trace Elements in Water
      and SRM 1598a Inorganic Constituents in Animal Serum (both certified for Mn), and
      SRM 955c Toxic Metals in Caprine Blood - Level 1 (not certified for Mn). Various
      matrix effects in ICP-MS produced inaccurate results for SRM 1643e and discrepant
      results for SRM 955c. In the absence of a certified value for Mn in SRM 955c, we
      assigned a "consensus" value by combining data from the New York State Department
      of Health (NYS), the Centers for Disease Control and Prevention (CDC) and the
      Centre de toxicologie du Quebec (CTQ). With this interlaboratory approach, we
      established an "all-lab" consensus value of 16.3 +/- 0.8 MUg L-1 based on data
      from DRC-ICP-MS with simple dilution sample preparation and blood-based
      calibration. We also assigned an "all-method" consensus value of 16.3 +/- 0.9 MUg
      L-1 based on GFAAS and SF-ICP-MS data from the NYS lab and the DRC-ICP-MS all-lab
      consensus value. Although the expanded uncertainty (U) calculated for the
      consensus values may not fully account for all sources of uncertainty, it does
      show the relative variation that might be expected from one study to the next for
      the determination of Mn in blood.

PMID- 26290620
TI  - Prevention of Mental Disorder in Older Adults: Recent Innovations and Future
      Directions.
AB  - As the global population is aging, increased efforts should be placed on
      preventing mental disorders in older adults, as opposed to just focusing on
      sickness and treatment. We provide an overview of existing innovations in
      prevention in the domains of pharmacotherapy, psychotherapy, and psychosocial
      interventions. These programs have shown that depression and anxiety can be
      prevented from recurring, incidence of new disorder can be reduced, and general
      mental health can be promoted. We also give direction for future research to move
      the field of geriatric mental health prevention forward.

PMID- 26290621
TI  - Tree cover at fine and coarse spatial grains interacts with shade tolerance to
      shape plant species distributions across the Alps.
AB  - The role of competition for light among plants has long been recognised at local
      scales, but its importance for plant species distributions at larger spatial
      scales has generally been ignored. Tree cover modifies the local abiotic
      conditions below the canopy, notably by reducing light availability, and thus,
      also the performance of species that are not adapted to low-light conditions.
      However, this local effect may propagate to coarser spatial grains, by affecting
      colonisation probabilities and local extinction risks of herbs and shrubs. To
      assess the effect of tree cover at both the plot- and landscape-grain sizes
      (approximately 10-m and 1-km), we fit Generalised Linear Models (GLMs) for the
      plot-level distributions of 960 species of herbs and shrubs using 6,935
      vegetation plots across the European Alps. We ran four models with different
      combinations of variables (climate, soil and tree cover) at both spatial grains
      for each species. We used partial regressions to evaluate the independent effects
      of plot- and landscape-grain tree cover on plot-level plant communities. Finally,
      the effects on species-specific elevational range limits were assessed by
      simulating a removal experiment comparing the species distributions under high
      and low tree cover. Accounting for tree cover improved the model performance,
      with the probability of the presence of shade-tolerant species increasing with
      increasing tree cover, whereas shade-intolerant species showed the opposite
      pattern. The tree cover effect occurred consistently at both the plot and
      landscape spatial grains, albeit most strongly at the former. Importantly, tree
      cover at the two grain sizes had partially independent effects on plot-level
      plant communities. With high tree cover, shade-intolerant species exhibited
      narrower elevational ranges than with low tree cover whereas shade-tolerant
      species showed wider elevational ranges at both limits. These findings suggest
      that forecasts of climate-related range shifts for herb and shrub species may be
      modified by tree cover dynamics.

PMID- 26290622
TI  - A Longitudinal Examination of the Hopelessness Theory of Depression in People Who
      Have Multiple Sclerosis.
AB  - PURPOSE: Hopelessness theory predicts that negative attributional style will
      interact with negative life events over time to predict depression. The intention
      of this study was to test this in a population who are at greater risk of
      negative life events, people with Multiple Sclerosis (MS). METHOD: Data,
      including measures of attributional style, negative life events, and depressive
      symptoms, were collected via postal survey in 3 phases, each one a year apart.
      RESULTS: Responses were received from over 380 participants at each study phase.
      Negative attributional style was consistently able to predict future depressive
      symptoms at low to moderate levels of association; however, this ability was not
      sustained when depressive symptoms at Phase 1 were controlled for. No substantial
      evidence to support the hypothesised interaction of negative attributional style
      and negative life events was found. CONCLUSIONS: Findings were not supportive of
      the causal interaction proposed by the hopelessness theory of depression. Further
      work considering other time frames, using methods to prime attributional style
      before assessment and specifically assessing the hopelessness subtype of
      depression, may prove to be more fruitful. Intervention directly to address
      attributional style should also be considered.

PMID- 26290623
TI  - The Effect of Spatial Working Memory Deterioration on Strategic Visuomotor
      Learning across Aging.
AB  - OBJECTIVE: To evaluate the effect of age-related cognitive changes in a
      visuomotor learning task that depends on strategic control and contrast it with
      the effect in a task principally depending on visuomotor recalibration. METHODS:
      Participants performed a ball throwing task while donning either a reversing dove
      prism or a displacement wedge prism, which mainly depend on strategic control or
      visuomotor recalibration, respectively. Visuomotor performance was then analysed
      in relation to rule acquisition and reversal, recognition memory, visual memory,
      spatial planning, and spatial working memory with tasks from the Cambridge
      Neuropsychological Test Automated Battery (CANTAB). RESULTS: The results
      confirmed previous works showing a detrimental effect of age on visuomotor
      learning. The analyses of the cognitive changes observed across age showed that
      both strategic control and visuomotor recalibration had significant negative
      correlations only with the number of errors in the spatial working memory task.
      However, when the effect of aging was controlled, the only significant
      correlation remaining was between the reversal adaptation magnitude and spatial
      working memory. DISCUSSION: These results suggest that spatial working memory
      decline across aging could contribute to age-dependent deterioration in both
      visuomotor learning processes. However, spatial working memory integrity seems to
      affect strategic learning decline even after controlling for aging.

PMID- 26290624
TI  - Inflammatory Response to Traumatic Injury: Clinical and Animal Researches in
      Inflammation.

PMID- 26290625
TI  - Surging Hormones: Brain-Behavior Interactions During Puberty.
AB  - In this paper we discuss the surging hormones of puberty and their influences on
      adolescent behavior. We describe why these issues represent an interesting and
      important area of investigation, emphasizing their contributions to a specific
      set of developmental processes at the heart of the transition from childhood to
      adolescence. We briefly review the neuroendocrine underpinnings of human puberty.
      Our review focuses on evidence for behavioral (and neurobehavioral) effects of
      gonadal hormones, and emphasizes the social and affective dimensions of these
      hormonal effects. More broadly, we consider how these hormonal events contribute
      to brain-behavior interactions that can bias early adolescent trajectories in
      both positive and negative directions, and in ways that may begin as small
      influences, but can spiral into large-scale effects over time. These influences
      also appear to play an important role in functional and structural brain
      development during adolescence. Finally we offer some thoughts on directions for
      future research in these areas.

PMID- 26290626
TI  - How prevention curricula are taught under real-world conditions: Types of and
      reasons for teacher curriculum adaptations.
AB  - PURPOSE: As interventions are disseminated widely, issues of fidelity and
      adaptation become increasingly critical to understand. This study aims to
      describe the types of adaptations made by teachers delivering a school-based
      substance use prevention curriculum and their reasons for adapting program
      content. DESIGN/METHODOLOGY/APPROACH: To determine the degree to which
      implementers adhere to a prevention curriculum, naturally adapt the curriculum,
      and the reasons implementers give for making adaptations, the study examined
      lesson adaptations made by the 31 teachers who implemented the keepin' it REAL
      drug prevention curriculum in 7th grade classrooms (n = 25 schools). Data were
      collected from teacher self-reports after each lesson and observer coding of
      videotaped lessons. From the total sample, 276 lesson videos were randomly
      selected for observational analysis. FINDINGS: Teachers self-reported adapting
      more than 68 percent of prevention lessons, while independent observers reported
      more than 97 percent of the observed lessons were adapted in some way. Types of
      adaptations included: altering the delivery of the lesson by revising the
      delivery timetable or delivery context; changing content of the lesson by
      removing, partially covering, revising, or adding content; and altering the
      designated format of the lesson (such as assigning small group activities to
      students as individual work). Reasons for adaptation included responding to
      constraints (time, institutional, personal, and technical), and responding to
      student needs (students' abilities to process curriculum content, to enhance
      student engagement with material). RESEARCH LIMITATIONS/IMPLICATIONS: The study
      sample was limited to rural schools in the US mid-Atlantic; however, the results
      suggest that if programs are to be effectively implemented, program developers
      need a better understanding of the types of adaptations and reasons implementers
      provide for adapting curricula. PRACTICAL IMPLICATIONS: These descriptive data
      suggest that prevention curricula be developed in shorter teaching modules,
      developers reconsider the usefulness of homework, and implementer training and
      ongoing support might benefit from more attention to different implementation
      styles. ORIGINALITY/VALUE: With nearly half of US public schools implementing
      some form of evidence-based substance use prevention program, issues of
      implementation fidelity and adaptation have become paramount in the field of
      prevention. The findings from this study reveal the complexity of the types of
      adaptations teachers make naturally in the classroom to evidence-based curricula
      and provide reasons for these adaptations. This information should prove useful
      for prevention researchers, program developers, and health educators alike.

PMID- 26290628
TI  - Therapeutic potential of small interfering RNAs/micro interfering RNA in
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer
      and represents the third leading cause of cancer-related death worldwide. Current
      available therapeutic approaches are poorly effective, especially for the
      advanced forms of the disease. In the last year, short double stranded RNA
      molecules termed small interfering RNAs (siRNAs) and micro interfering RNAs
      (miRNA), emerged as interesting molecules with potential therapeutic value for
      HCC. The practical use of these molecules is however limited by the
      identification of optimal molecular targets and especially by the lack of
      effective and targeted HCC delivery systems. Here we focus our discussion on the
      most recent advances in the identification of siRNAs/miRNAs molecular targets and
      on the development of suitable siRNA/miRNAs delivery systems. 

PMID- 26290627
TI  - Signs and genetics of rare cancer syndromes with gastroenterological features.
AB  - Although the genetic bases of most hereditary cancer syndromes are known, and
      genetic tests are available for them, the incidence of the most rare of these
      syndromes is likely underestimated, partially because the clinical expression is
      neither fully understood nor easily diagnosed due to the variable and complex
      expressivity. The clinical features of a small pool of rare cancer syndromes
      include gastroenterological signs, though not necessarily tumors, that could
      require the intervention of a gastroenterologist during any of the phases of the
      clinical management. Herein we will attempt to spread the knowledge on these rare
      syndromes by summarizing the phenotype and genetic basis, and revising the
      peculiar gastroenterological signs whose underlying role in these rare hereditary
      cancer syndromes is often neglected. Close collaboration between geneticists and
      gastroenterologists could facilitate both the early identification of patients or
      relatives at-risk and the planning of multidisciplinary and tailored management
      of these subjects. 

PMID- 26290629
TI  - Rectal cancer and Fournier's gangrene - current knowledge and therapeutic
      options.
AB  - Fournier's gangrene (FG) is a rapid progressive bacterial infection that involves
      the subcutaneous fascia and part of the deep fascia but spares the muscle in the
      scrotal, perianal and perineal region. The incidence has increased dramatically,
      while the reported incidence of rectal cancer-induced FG is unknown but is
      extremely low. Pathophysiology and clinical presentation of rectal cancer-induced
      FG per se does not differ from the other causes. Only rectal cancer-specific
      symptoms before presentation can lead to the diagnosis. The diagnosis of rectal
      cancer-induced FG should be excluded in every patient with blood on digital
      rectal examination, when urogenital and dermatological causes are excluded and
      when fever or sepsis of unknown origin is present with perianal symptomatology.
      Therapeutic options are more complex than for other forms of FG. First, the
      causative rectal tumor should be removed. The survival of patients with rectal
      cancer resection is reported as 100%, while with colostomy it is 80%. The
      preferred method of rectal resection has not been defined. Second, oncological
      treatment should be administered but the timing should be adjusted to the
      resolution of the FG and sometimes for the healing of plastic reconstructive
      procedures that are commonly needed for the reconstruction of large perineal,
      scrotal and lower abdominal wall defects. 

PMID- 26290632
TI  - Calcium glycerophosphate preserves transepithelial integrity in the Caco-2 model
      of intestinal transport.
AB  - AIM: To assess the direct effects of ischemia on intestinal epithelial integrity.
      Furthermore, clinical efforts at mitigating the effect of hypoperfusion on gut
      permeability have focused on restoring gut vascular function. METHODS: We report
      that, in the Caco-2 cell model of transepithelial transport, calcium
      glycerophosphate (CGP), an inhibitor of intestinal alkaline phosphatase F3, has a
      significant effect to preserve transepithelial electrical resistance (TEER) and
      to attenuate increases in mannitol flux rates during hypoxia or cytokine
      stimulation. RESULTS: The effect was observable even at concentrations as low as
      1 MUmol/L. As celiac disease is also marked by a loss of gut epithelial
      integrity, the effect of CGP to attenuate the effect of the alpha-gliadin peptide
      31-55 was also examined. In this instance, CGP exerted little effect of
      preservation of TEER, but significantly attenuated peptide induced increase in
      mannitol flux. CONCLUSION: It appears that CGP treatment might synergize with
      other therapies to preserve gut epithelial integrity.

PMID- 26290630
TI  - Epigenetic regulation of DNA repair machinery in Helicobacter pylori-induced
      gastric carcinogenesis.
AB  - Although thousands of DNA damaging events occur in each cell every day, efficient
      DNA repair pathways have evolved to counteract them. The DNA repair machinery
      plays a key role in maintaining genomic stability by avoiding the maintenance of
      mutations. The DNA repair enzymes continuously monitor the chromosomes to correct
      any damage that is caused by exogenous and endogenous mutagens. If DNA damage in
      proliferating cells is not repaired because of an inadequate expression of DNA
      repair genes, it might increase the risk of cancer. In addition to mutations,
      which can be either inherited or somatically acquired, epigenetic silencing of
      DNA repair genes has been associated with carcinogenesis. Gastric cancer
      represents the second highest cause of cancer mortality worldwide. The disease
      develops from the accumulation of several genetic and epigenetic changes during
      the lifetime. Among the risk factors, Helicobacter pylori (H. pylori) infection
      is considered the main driving factor to gastric cancer development. Thus, in
      this review, we summarize the current knowledge of the role of H. pylori
      infection on the epigenetic regulation of DNA repair machinery in gastric
      carcinogenesis. 

PMID- 26290631
TI  - Outcome of stenting in biliary and pancreatic benign and malignant diseases: A
      comprehensive review.
AB  - Endoscopic stenting has become a widely method for the management of various
      malignant and benign pancreatico-biliary disorders. Biliary and pancreatic stents
      are devices made of plastic or metal used primarily to establish patency of an
      obstructed bile or pancreatic duct and may also be used to treat biliary or
      pancreatic leaks, pancreatic fluid collections and to prevent post-endoscopic
      retrograde cholangiopancreatography pancreatitis. In this review, relevant
      literature search and expert opinions have been used to evaluate the outcome of
      stenting in biliary and pancreatic benign and malignant diseases. 

PMID- 26290633
TI  - Female spontaneously diabetic Torii fatty rats develop nonalcoholic
      steatohepatitis-like hepatic lesions.
AB  - AIM: To investigate the histological features of the liver in spontaneously
      diabetic Torii (SDT) fatty rats compared with age-matched Sprague-Dawley (SD)
      rats. METHODS: Female SDT Lepr(fa) (SDT fatty) rats and age-matched SD rats were
      fed ad libitum. Body weight and biochemical parameters, such as serum glucose,
      triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT) and
      aspartate aminotransferase (AST) levels as well as fatty acid and TG accumulation
      in the liver were evaluated at 8 wk of age in the non-fasting state and at 8-wk
      intervals from 8 to 40 wk of age. Histopathological examinations of the liver
      were performed using hematoxylin and eosin and Sirius Red staining as well as
      double staining for ED-1 and toluidine blue. The expression of genes involved in
      TG synthesis, inflammation, and fibrosis was examined in the liver. RESULTS: SDT
      fatty rats showed significantly increased body weight compared with SD rats.
      Serum glucose, TG, and TC levels were significantly higher in SDT fatty rats
      compared with SD rats. The serum AST and ALT levels in SDT fatty rats were
      significantly elevated at 8 wk of age compared with the levels in SD rats.
      Hepatic TG content was marked in SDT fatty rats from 8 to 32 wk of age.
      Histopathologically, severe hepatosteatosis accompanied by inflammation was
      observed at 8 wk of age, and fibrosis started to occur at 32 wk of age.
      Furthermore, Sirius Red and ED-1 staining were increased in the liver at 32 wk of
      age. Hepatic gene expression related to TG synthesis, inflammation and fibrosis
      tended to increase in SDT fatty rats compared with SD rats, and the gene
      expression related to TG secretion was decreased in SDT fatty rats compared with
      SD rats. CONCLUSION: Female SDT fatty rats have the potential to become an
      important animal model of nonalcoholic steatohepatitis with type 2 diabetes and
      obesity.

PMID- 26290634
TI  - Protective effect of Salvia miltiorrhiza and Carthamus tinctorius extract against
      lipopolysaccharide-induced liver injury.
AB  - AIM: To investigate the hepatoprotective effects and mechanisms of an extract of
      Salvia miltiorrhiza and Carthamus tinctorius in vivo. METHODS: C57BL/6J mice were
      randomly assigned to five groups and intraperitoneally administered 0.9% saline,
      Salvia miltiorrhiza and Carthamus tinctorius extract [Danhong injection (DHI),
      0.75 and 3 g/kg mixed extract] or reduced glutathione for injection (RGI, 300
      mg/kg) for 30 min before exposure to lipopolysaccharide (LPS, 16 mg/kg). After
      intraperitoneal LPS stimulation for 90 min or 6 h, the mice were sacrificed by
      ether anaesthesia, and serum and liver samples were collected. Histological
      analysis (H&E) and terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labelling (TUNEL) staining were performed. Alanine transferase (ALT), aspartate
      transaminase (AST), total bilirubin (TBil), glutathione-S-transferase (GST),
      malondialdehyde (MDA), tumour necrosis factor (TNF)-alpha, interleukin (IL)-6,
      and caspase-3 levels were measured. Bax, Bcl-2, P-IkappaBalpha, IkappaBalpha, P
      NF-kappaB p65, and NF-kappaB p65 protein levels were determined by Western blot.
      TNF-alpha, IL-6, caspase-3, Bax and Bcl-2 mRNA expression was measured by real
      time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS:
      Hematoxylin-eosin staining and TUNEL results suggested that DHI (3 g/kg)
      treatment alleviated inflammatory and apoptotic (P < 0.01) injury in the liver of
      mice. DHI treatment dose-dependently blunted the abnormal changes in biochemical
      parameters such as ALT (72.53 +/- 2.83 for 3 g/kg, P < 0.01), AST (76.97 +/- 5.00
      for 3 g/kg, P < 0.01), TBil (1.17 +/- 0.10 for 3 g/kg, P < 0.01), MDA (0.81 +/-
      0.36 for 3 g/kg, P < 0.01), and GST (358.86 +/- 12.09 for 3 g/kg, P < 0.01).
      Moreover, DHI (3 g/kg) remarkably decreased LPS-induced protein expression of TNF
      alpha (340.55 +/- 10.18 for 3 g/kg, P < 0.01), IL-6 (261.34 +/- 10.18 for 3 g/kg,
      P < 0.01), and enzyme activity of caspase-3 (0.93 +/- 0.029 for 3 g/kg, P <
      0.01). The LPS-induced mRNA expression of TNF-alpha, IL-6 and caspase-3 was also
      decreased by DHI. Western blot analysis revealed that DHI antagonised LPS
      stimulated decrease of Bcl-2 and increase of Bax protein expression. Furthermore,
      DHI inhibited LPS-induced IkappaBalpha and NF-kappaB p65 phosphorylation.
      CONCLUSION: DHI may be a multi-function protectant against acute hepatic injury
      in mice through its anti-inflammatory, anti-oxidative and anti-apoptotic
      activities.

PMID- 26290635
TI  - Mechanisms of pyruvate kinase M2 isoform inhibits cell motility in hepatocellular
      carcinoma cells.
AB  - AIM: To investigate biological mechanisms underlying pyruvate kinase M2 isoform
      (PKM2) regulation of cell migration and invasion in hepatocellular carcinoma
      cells. METHODS: HepG2 and Huh-7 hepatocellular carcinoma cell lines were stably
      transfected and cultured in DMEM (HyClone, Logan, UT, United States). To
      investigate the effects of PKM2 on cellular proliferation, hepatocellular
      carcinoma cells were subjected to the Cell Counting Kit-8 (Dojindo, Kamimashiki
      gun, Kumamoto, Japan). And investigate the effects of PKM2 on cell signal pathway
      related with migration and invasion, Western immunoblotting were used to find out
      the differential proteins. All the antibody used was purchaseed from Cell Signal
      Technology. In order to explore cell motility used Transwell invasion and wound
      healing assays. The transwell plate with 0.5 mg/mL collagen type I (BD
      Bioscience, San Jose, CA)-coated filters. The wound-healing assay was performed
      in 6-well plates. Total RNA was extracted using TRIzol reagent (Invitrogen, CA,
      United States) and then reverse transcription was conducted. Quantitative reverse
      transcription-polymerase chain reaction (PCR) analysis was performed with the ABI
      7500 real-time PCR system (Applied Biosystems). We further use digital gene
      expression tag profiling and identification of differentially expressed genes.
      RESULTS: The cells seeded in four 96-well plates were measured OD450 by conducted
      Cell Counting Kit-8. From this conduction we observed that both HepG2 and Huh-7
      hepatocellular carcinoma cells with silenced PKM2 turn on a proliferate
      inhibition; however, cell migration and invasion were enhanced compared with the
      control upon stimulation with epidermal growth factor (EGF). Our results indicate
      that the knockdown of PKM2 decreased the expression of E-cadherin and enhanced
      the activity of the EGF/EGFR signaling pathway, furthermore up-regulate the
      subsequent signal molecular the PLCgamma1 and extracellular signal-regulated
      kinase 1/2 expression in the hepatocellular carcinoma cell lines HepG2 and Huh-7,
      which regulates cell motility. These variations we observed were due to the
      activation of the transforming growth factor beta (TGFbeta) signaling pathway
      after PKM2 knockdown. We also found that the expression of TGFBRI was increased
      and the phosphorylation of Smad2 was enhanced. Taken together, our findings
      demonstrate that PKM2 can regulate cell motility through the EGF/EGFR and
      TGFbeta/TGFR signaling pathways in hepatocellular carcinoma cells. CONCLUSION:
      PKM2 play different roles in modulating the proliferation and metastasis of
      hepatocellular carcinoma cells, and this finding could help to guide the future
      targeted therapies.

PMID- 26290636
TI  - Endozepine-4 levels are increased in hepatic coma.
AB  - AIM: To evaluate the serum levels of endozepine-4, their relation with ammonia
      serum levels, the grading of coma and the severity of cirrhosis, in patients with
      hepatic coma. METHODS: In this study we included 20 subjects with Hepatic coma,
      20 subjects with minimal hepatic encephalopathy (MHE) and 20 subjects control.
      All subjects underwent blood analysis, Child Pugh and Model for End - stage liver
      disease (MELD) assessment, endozepine-4 analysis. RESULTS: Subjects with hepatic
      coma showed significant difference in endozepine-4 (P < 0.001) and NH3 levels (P
      < 0.001) compared both to MHE and controls patients. Between NH3 and endozepine-4
      we observed a significant correlation (P = 0.009; Pearson correlation 0.570).
      There was a significant correlation between endozepine-4 and MELD (P = 0.017;
      Pearson correlation = 0.529). In our study blood ammonia concentration was noted
      to be raised in patients with hepatic coma, with the highest ammonia levels being
      found in those who were comatose. We also found a high correlation between
      endozepine-4 and ammonia (P < 0.001). In patients with grade IV hepatic coma,
      endozepine levels were significantly higher compared to other groups. CONCLUSION:
      This study suggests that an increased level of endozepine in subjects with higher
      levels of MELD was observed. In conclusion, data concerning involvement of the
      GABA-ergic system in HE coma could be explained by stage-specific alterations.

PMID- 26290637
TI  - Pre-lung transplant measures of reflux on impedance are superior to pH testing
      alone in predicting early allograft injury.
AB  - AIM: To evaluate pre-lung transplant acid reflux on pH-testing vs corresponding
      bolus reflux on multichannel intraluminal impedance (MII) to predict early
      allograft injury. METHODS: This was a retrospective cohort study of lung
      transplant recipients who underwent pre-transplant combined MII-pH-testing at a
      tertiary care center from January 2007 to November 2012. Patients with pre
      transplant fundoplication were excluded. Time-to-event analysis was performed
      using a Cox proportional hazards model to assess associations between measures of
      reflux on MII-pH testing and early allograft injury. Area under the receiver
      operating characteristic (ROC) curve (c-statistic) of the Cox model was
      calculated to assess the predictive value of each reflux parameter for early
      allograft injury. Six pH-testing parameters and their corresponding MII measures
      were specified a priori. The pH parameters were upright, recumbent, and overall
      acid reflux exposure; elevated acid reflux exposure; total acid reflux episodes;
      and acid clearance time. The corresponding MII measures were upright, recumbent,
      and overall bolus reflux exposure; elevated bolus reflux exposure; total bolus
      reflux episodes; and bolus clearance time. RESULTS: Thirty-two subjects (47% men,
      mean age: 55 years old) met the inclusion criteria of the study. Idiopathic
      pulmonary fibrosis (46.9%) represented the most common pulmonary diagnosis
      leading to transplantation. Baseline demographics, pre-transplant cardiopulmonary
      function, number of lungs transplanted (unilateral vs bilateral), and post
      transplant proton pump inhibitor use were similar between reflux severity groups.
      The area under the ROC curve, or c-statistic, of each acid reflux parameter on
      pre-transplant pH-testing was lower than its bolus reflux counterpart on MII in
      the prediction of early allograft injury. In addition, the development of early
      allograft injury was significantly associated with three pre-transplant MII
      measures of bolus reflux: overall reflux exposure (HR = 1.18, 95%CI: 1.01-1.36, P
      = 0.03), recumbent reflux exposure (HR = 1.25, 95%CI: 1.04-1.50, P = 0.01) and
      bolus clearance (HR = 1.09, 95%CI: 1.01-1.17, P = 0.02), but not with any pH
      testing parameter measuring acid reflux alone. CONCLUSION: Pre-transplant MII
      measures of bolus reflux perform better than their pH-testing counterparts in
      predicting early allograft injury post-lung transplantation.

PMID- 26290638
TI  - Diagnostic value of drain amylase for detecting intrathoracic leakage after
      esophagectomy.
AB  - AIM: To investigate the value of elevated drain amylase concentrations for
      detecting anastomotic leakage (AL) after minimally invasive Ivor-Lewis
      esophagectomy (MI-ILE). METHODS: This was a retrospective analysis of
      prospectively collected data in two hospitals in the Netherlands. Consecutive
      patients undergoing MI-ILE were included. A Jackson-Pratt drain next to the
      dorsal side of the anastomosis and bilateral chest drains were placed at the end
      of the thoracoscopic procedure. Amylase levels in drain fluid were determined in
      all patients during at least the first four postoperative days. Contrast computed
      tomography scans and/or endoscopic imaging were performed in cases of a
      clinically suspected AL. Anastomotic leakage was defined as any sign of leakage
      of the esophago-gastric anastomosis on endoscopy, re-operation, radiographic
      investigations, post mortal examination or when gastro-intestinal contents were
      found in drain fluid. Receiver operator characteristic curves were used to
      determine the cut-off values. Sensitivity, specificity, positive predictive
      value, negative predictive value, risk ratio and overall test accuracy were
      calculated for elevated drain amylase concentrations. RESULTS: A total of 89
      patients were included between March 2013 and August 2014. No differences in
      group characteristics were observed between patients with and without AL, except
      for age. Patients with AL were older than were patients without AL (P = 0.01).
      One patient (1.1%) without AL died within 30 d after surgery due to pneumonia and
      acute respiratory distress syndrome. Anastomotic leakage that required any
      intervention occurred in 15 patients (16.9%). Patients with proven anastomotic
      leakage had higher drain amylase levels than patients without anastomotic leakage
      [median 384 IU/L (IQR 34-6263) vs median 37 IU/L (IQR 26-66), P = 0.003]. Optimal
      cut-off values on postoperative days 1, 2, and 3 were 350 IU/L, 200 IU/L and 160
      IU/L, respectively. An elevated amylase level was found in 9 of the 15 patients
      with AL. Five of these 9 patients had early elevations of their amylase levels,
      with a median of 2 d (IQR 2-5) before signs and symptoms occurred. CONCLUSION:
      Measurement of drain amylase levels is an inexpensive and easy tool that may be
      used to screen for anastomotic leakage soon after MI-ILE. However, clinical
      validation of this marker is necessary.

PMID- 26290639
TI  - Cardiac mucosa at the gastroesophageal junction: An Eastern perspective.
AB  - AIM: To investigate the nature and origin of cardiac mucosa (CM). METHODS: Biopsy
      samples from sixty-one individuals were included in this study. The specimens
      were taken "at", "just below", or "just above" the gastroesophageal junction,
      including the histologic squamocolumnar junction. Clinical data were obtained by
      reviewing electronic medical records for each patient. Patients with a history of
      stomach adenoma or carcinoma and esophageal carcinoma were excluded, and cases
      that were endoscopically suspicious of Barrett's esophagus or a polyp were also
      ruled out. Histologic and endoscopic reviews were performed blinded to the
      patient's clinical data. Histologic evaluation was conducted by two pathologists,
      and endoscopic review was performed by a endoscopist with wide experience in the
      field. Histologically, the columnar epithelium of squamocolumnar junction,
      presence and severity of acute and chronic inflammation, atrophy, intestinal
      metaplasia, and presence of carditis were evaluated. Endoscopically, reflux
      esophagitis was evaluated by Los Angeles (LA) classification, hiatal hernias were
      classified by Hill grade, and gastroesophageal flap valves were assessed.
      RESULTS: Fifty-nine of the 61 (96.7%) patients were Korean; 65.6% (40/61) of the
      patients underwent endoscopy according to the schedule of the National Health
      Insurance Program as a screening inspection. Of these, only 20.0% (8/40) of cases
      had reflux symptoms. CM was present in 41/61 (67.2%) individuals, and its
      presence was associated with older age compared to oxyntocardiac mucosa/oxyntic
      mucosa (60.59 +/- 2.02 years vs 51.55 +/- 3.35 years; P = 0.018). The presence of
      CM was associated with endoscopic diagnosis of esophagitis according to the LA
      classification (P = 0.022). CM was associated with mononuclear cell infiltration
      and neutrophilic infiltration, which were statistically significant (P = 0.001,
      and P = 0.004, respectively). The inflammation of CM, "carditis", showed a
      statistically significant association with endoscopic diagnosis of reflux
      esophagitis according to the LA classification (P = 0.008). CONCLUSION: CM at the
      gastroesophageal junction is a common histologic finding in biopsy specimens,
      though not always present, and associated with gastroesophageal reflux disease
      and carditis severity.

PMID- 26290640
TI  - Predictors of the patency of self-expandable metallic stents in malignant
      gastroduodenal obstruction.
AB  - AIM: To investigate the predictive factors of self-expandable metallic stent
      patency after stent placement in patients with inoperable malignant
      gastroduodenal obstruction. METHODS: A total of 116 patients underwent stent
      placements for inoperable malignant gastroduodenal obstruction at a tertiary
      academic center. Clinical success was defined as acceptable decompression of the
      obstructive lesion within the malignant gastroduodenal neoplasm. We evaluated
      patient comorbidities and clinical statuses using the World Health Organization's
      scoring system and categorized patient responses to chemotherapy using the
      Response Evaluation Criteria in Solid Tumors criteria. We analyzed the
      relationships between possible predictive factors and stent patency. RESULTS:
      Self-expandable metallic stent placement was technically successful in all
      patients (100%), and the clinical success rate was 84.2%. In a multivariate Cox
      proportional hazards model, carcinoembryonic antigen (CEA) levels were correlated
      with a reduction in stent patency [P = 0.006; adjusted hazard ratio (aHR) = 2.92,
      95%CI: 1.36-6.25]. Palliative chemotherapy was statistically associated with an
      increase in stent patency (P = 0.009; aHR = 0.27, 95%CI: 0.10-0.72). CONCLUSION:
      CEA levels can easily be measured at the time of stent placement and may help
      clinicians to predict stent patency and determine the appropriate stent
      procedure.

PMID- 26290641
TI  - Full-thickness excision using transanal endoscopic microsurgery for treatment of
      rectal neuroendocrine tumors.
AB  - AIM: To assess the efficacy of full-thickness excision using transanal endoscopic
      microsurgery (TEM) in the treatment of rectal neuroendocrine tumors. METHODS: We
      analyzed the data of all rectal neuroendocrine tumor patients who underwent local
      full-thickness excision using TEM between December 2006 and December 2014 at our
      department. Data collected included patient demographics, tumor characteristics,
      operative details, postoperative outcomes, pathologic findings, and follow-ups.
      RESULTS: Full-thickness excision using TEM was performed as a primary excision (n
      = 38) or as complete surgery after incomplete resection by endoscopic polypectomy
      (n = 21). The mean size of a primary tumor was 0.96 +/- 0.21 cm, and the mean
      distance of the tumor from the anal verge was 8.4 +/- 1.4 cm. The mean duration
      of the operation was 57.6 +/- 13.7 min, and the mean blood loss was 13.5 +/- 6.6
      mL. No minor morbidities, transient fecal incontinence, or wound dehiscence was
      found. Histopathologically, all tumors showed typical histology without lymphatic
      or vessel infiltration, and both deep and lateral surgical margins were
      completely free of tumors. Among 21 cases of complete surgery after endoscopic
      polypectomy, 9 were histologically shown to have a residual tumor in the
      specimens obtained by TEM. No additional radical surgery was performed. No
      recurrence was noted during the median of 3 years' follow-up. CONCLUSION: Full
      thickness excision using TEM could be a first surgical option for complete
      removal of upper small rectal neuroendocrine tumors.

PMID- 26290642
TI  - Impact of a clinical pathway on treatment outcome in patients with acute
      pancreatitis.
AB  - AIM: To determine the impact of a clinical pathway (CP) on acute pancreatitis
      (AP) treatment outcome. METHODS: A retrospective analysis of medical records was
      performed. We compared the results of AP treatment outcome over two time periods
      in our centre, before (2006-2007) and after (2010-2012) the implementation of a
      CP. The CP comprised the following indicators of quality: performance of all
      laboratory tests on admission (including lipids and carbohydrate deficient
      transferrin), determination of AP aetiology, abdomen ultrasound (US) within the
      first 24 h after admission, contrast-enhanced computed tomography of the abdomen
      in all cases of suspected pancreatic necrosis, appropriately selected and
      sufficiently used antibiotic therapy (if necessary), pain control, adequate
      hydration, control of haemodynamic parameters and transfer to the Intensive Care
      Unit (ICU) (if necessary), endoscopic retrograde cholangiopancreatography (ERCP)
      in biliary AP, surgical treatment (if necessary), and advice on outpatient follow
      up after discharge. A comparison of the length of stay with that in other
      Slovenian hospitals was also performed. RESULTS: There were 139 patients treated
      in the three-year period after the introduction of a CP, of which 81 (58.3%) were
      male and 58 (41.7%) female. The patients' mean age was 59.6 +/- 17.3 years. The
      most common aetiologies were alcoholism and gallstones (38.8% each), followed by
      unexplained (11.5%), drug-induced, hypertriglyceridemia, post ERCP (2.9% each)
      and tumours (2.2%). Antibiotic therapy was prescribed in 72 (51.8%) patients.
      Abdominal US was performed in all patients within the first 24 h after admission.
      Thirty-two (23.0%) patients were treated in the ICU. Four patients died (2.9%).
      In comparison to 2006-2007, we found an increased number of alcoholic and biliary
      AP and an associated decrease in the number of unexplained aetiology cases. The
      use of antibiotics also significantly decreased after the implementation of a CP
      (from 70.3% to 51.8%; P = 0.003). There was no statistically significant
      difference in mortality (1.8% vs 2.9%). The length of stay was significantly
      shorter when compared to the Slovenian average (P = 0.018). CONCLUSION: The
      introduction of a CP has improved the treatment of patients with AP, as assessed
      by all of the observed parameters.

PMID- 26290643
TI  - Magnifying narrow-band imaging endoscopy is superior in diagnosis of early
      gastric cancer.
AB  - AIM: To evaluate the diagnostic effectiveness of white light endoscopy,
      magnifying endoscopy (ME), and magnifying narrow-band imaging endoscopy (ME-NBI)
      in detecting early gastric cancer (EGC). METHODS: From March 2010 to June 2012, a
      total of 3616 patients received screening for gastric cancer by magnifying
      endoscopy. There were 3675 focal gastric lesions detected using conventional high
      definition white light endoscopy (HD-WLE) in four different referential hospitals
      that were recruited for further investigation using ME and ME-NBI. The images
      obtained from HD-WLE, ME, and ME-NBI were reviewed by four experienced
      endoscopists to evaluate their diagnostic effectiveness for EGC. The diagnosis of
      cancerous and non-cancerous lesions was conducted by evaluating the microvascular
      and microsurface patterns using the VS classification system. The final
      endoscopic diagnosis of each lesion was determined by consultation when a
      disagreement occurred. We used histopathological results as the gold standard for
      the diagnosis of EGC. RESULTS: Among the 3675 lesions found, 1508 were validated
      by pathological findings as chronic gastritis, 1279 as chronic gastritis with
      intestinal metaplasia, 631 as low-grade neoplasia, and 257 as EGC. The
      sensitivity, specificity, positive predictive value, negative predictive value,
      and accuracy of HD-WLE for the diagnosis of EGC were 71.2%, 99.1%, 85.5%, 97.9%
      and 97.1%, respectively. The results of ME for diagnosing EGC were 81.3%, 98.8%,
      83.3%, 98.6% and 97.6%, respectively. The results of ME-NBI for the diagnosis of
      EGC were 87.2%, 98.6%, 82.1%, 99.0% and 97.8%, respectively. The diagnostic
      sensitivity and accuracy of paired ME and ME-NBI were significantly better than
      those of HD-WLE (P < 0.05). CONCLUSION: HD-WLE has a relatively high accuracy for
      diagnosing EGC and is an effective screening tool. Further investigations of ME
      and ME-NBI are required to achieve superior accuracy.

PMID- 26290645
TI  - Peroral endoscopic myotomy for achalasia in patients aged >= 65 years.
AB  - AIM: To investigate the safety and efficacy of peroral endoscopic myotomy (POEM)
      for achalasia in patients aged >= 65 years. METHODS: From November 2011 to August
      2014, 15 consecutive patients (aged >= 65 years) diagnosed with achalasia were
      prospectively recruited and all underwent POEM at our institution. Eckardt score,
      lower esophageal sphincter (LES) pressure, esophageal diameter, SF-36
      questionnaire, and procedure-related complications were used to evaluate the
      outcomes. RESULTS: All 15 patients were treated successfully by POEM, with a
      median operation time of 55 min. Median myotomy length was 10 cm. Three patients
      underwent circular myotomy and 12 full-thickness myotomies. Symptoms remitted in
      all cases during post-POEM follow-up of 6-39 mo. Eckardt score reduced
      significantly (pre-operation vs post-operation: 8.0 vs 1.0, P < 0.05). Median LES
      pressure decreased from 27.4 to 9.6 mmHg (P < 0.05). Median diameter of the
      esophagus was significantly decreased (pre-operation vs post-operation: 51.0 mm
      vs 30.0 mm, P < 0.05). Only one patient had reflux, which was resolved with oral
      proton pump inhibitors. No serious complications related to POEM were found. The
      quality of life of the 15 patients improved significantly after POEM. CONCLUSION:
      POEM is a safe and effective technique for treatment of achalasia in patients
      aged >= 65 years, with improvement in symptoms and quality of life.

PMID- 26290644
TI  - Effectiveness and safety of first-generation protease inhibitors in clinical
      practice: Hepatitis C virus patients with advanced fibrosis.
AB  - AIM: To evaluates the effectiveness and safety of the first generation, NS3/4A
      protease inhibitors (PIs) in clinical practice against chronic C virus,
      especially in patients with advanced fibrosis. METHODS: Prospective study and non
      experimental analysis of a multicentre cohort of 38 Spanish hospitals that
      includes patients with chronic hepatitis C genotype 1, treatment-naive (TN) or
      treatment-experienced (TE), who underwent triple therapy with the first
      generation NS3/4A protease inhibitors, boceprevir (BOC) and telaprevir (TVR), in
      combination with pegylated interferon and ribavirin. The patients were treatment
      in routine practice settings. Data on the study population and on adverse
      clinical and virologic effects were compiled during the treatment period and
      during follow up. RESULTS: One thousand and fifty seven patients were included,
      405 (38%) were treated with BOC and 652 (62%) with TVR. Of this total, 30% (n =
      319) were TN and the remaining were TE: 28% (n = 298) relapsers, 12% (n = 123)
      partial responders (PR), 25% (n = 260) null-responders (NR) and for 5% (n = 57)
      with prior response unknown. The rate of sustained virologic response (SVR) by
      intention-to-treatment (ITT) was greater in those treated with TVR (65%) than in
      those treated with BOC (52%) (P < 0.0001), whereas by modified intention-to
      treatment (mITT) no were found significant differences. By degree of fibrosis,
      56% of patients were F4 and the highest SVR rates were recorded in the non-F4
      patients, both TN and TE. In the analysis by groups, the TN patients treated with
      TVR by ITT showed a higher SVR (P = 0.005). However, by mITT there were no
      significant differences between BOC and TVR. In the multivariate analysis by
      mITT, the significant SVR factors were relapsers, IL28B CC and non-F4; the type
      of treatment (BOC or TVR) was not significant. The lowest SVR values were
      presented by the F4-NR patients, treated with BOC (46%) or with TVR (45%). 28% of
      the patients interrupted the treatment, mainly by non-viral response (51%): this
      outcome was more frequent in the TE than in the TN patients (57% vs 40%, P =
      0.01). With respect to severe haematological disorders, neutropaenia was more
      likely to affect the patients treated with BOC (33% vs 20%, P <= 0.0001), and
      thrombocytopaenia and anaemia, the F4 patients (P = 0.000, P = 0.025,
      respectively). CONCLUSION: In a real clinical practice setting with a high
      proportion of patients with advanced fibrosis, effectiveness of first-generation
      PIs was high except for NR patients, with similar SVR rates being achieved by BOC
      and TVR.

PMID- 26290646
TI  - 0.025-inch vs 0.035-inch guide wires for wire-guided cannulation during
      endoscopic retrograde cholangiopancreatography: A randomized study.
AB  - AIM: To compare the clinical outcomes between 0.025-inch and 0.035-inch guide
      wires (GWs) when used in wire-guided cannulation (WGC). METHODS: A single center,
      randomized study was conducted between April 2011 and March 2013. This study was
      approved by the Medical Ethics Committee at our hospital. Informed, written
      consent was obtained from each patient prior to study enrollment. Three hundred
      and twenty-two patients with a naive papilla of Vater who underwent endoscopic
      retrograde cholangiopancreatography (ERCP) for the purpose of selective bile duct
      cannulation with WGC were enrolled in this study. Fifty-three patients were
      excluded based on the exclusion criteria, and 269 patients were randomly
      allocated to two groups by a computer and analyzed: the 0.025-inch GW group (n =
      109) and the 0.035-inch GW group (n = 160). The primary endpoint was the success
      rate of selective bile duct cannulation with WGC. Secondary endpoints were the
      success rates of the pancreatic GW technique and precutting, selective bile duct
      cannulation time, ERCP procedure time, the rate of pancreatic duct stent
      placement, the final success rate of selective bile duct cannulation, and the
      incidence of post-ERCP pancreatitis (PEP). RESULTS: The primary success rates of
      selective bile duct cannulation with WGC were 80.7% (88/109) and 86.3% (138/160)
      for the 0.025-inch and the 0.035-inch groups, respectively (P = 0.226). There
      were no statistically significant differences in the success rates of selective
      bile duct cannulation using the pancreatic duct GW technique (46.7% vs 52.4% for
      the 0.025-inch and 0.035-inch groups, respectively; P = 0.884) or in the success
      rates of selective bile duct cannulation using precutting (66.7% vs 63.6% for the
      0.025-inch and 0.035-inch groups, respectively; P = 0.893). The final success
      rates for selective bile duct cannulation using these procedures were 92.7%
      (101/109) and 97.5% (156/160) for the 0.025-inch and 0.035-inch groups,
      respectively (P = 0.113). There were no significant differences in selective bile
      duct cannulation time (median +/- interquartile range: 3.7 +/- 13.9 min vs 4.0 +/
      11.2 min for the 0.025-inch and 0.035-inch groups, respectively; P = 0.851),
      ERCP procedure time (median +/- interquartile range: 32 +/- 29 min vs 30 +/- 25
      min for the 0.025-inch and 0.035-inch groups, respectively; P = 0.184) or in the
      rate of pancreatic duct stent placement (14.7% vs 15.6% for the 0.025-inch and
      0.035-inch groups, respectively; P = 0.832). The incidence of PEP was 2.8%
      (3/109) and 2.5% (4/160) for the 0.025-inch and 0.035-inch groups, respectively
      (P = 0.793). CONCLUSION: The thickness of the GW for WGC does not appear to
      affect either the success rate of selective bile duct cannulation or the
      incidence of PEP.

PMID- 26290647
TI  - Antioxidant therapy in acute, chronic and post-endoscopic retrograde
      cholangiopancreatography pancreatitis: An updated systematic review and meta
      analysis.
AB  - AIM: To investigate the efficacy and adverse effects of antioxidant therapy in
      acute pancreatitis (AP), chronic pancreatitis (CP) and post-endoscopic retrograde
      cholangiopancreatography pancreatitis (PEP). METHODS: PubMed, Scopus, Google
      Scholar, Cochrane library database, and Evidence-based medicine/clinical trials
      published before August 2014 were searched. Clinical and laboratory outcomes of
      randomized trials of antioxidant therapy in patients with AP, CP and PEP were
      included. The methodological quality of the trials was assessed by the Jadad
      score based on the description of randomization, blinding, and dropouts
      (withdrawals). The results of the studies were pooled and meta-analyzed to
      provide estimates of the efficacy of antioxidant therapy. RESULTS: Thirty four
      trials out of 1069 potentially relevant studies with data for 4898 patients were
      eligible for inclusion. Antioxidant therapy significantly reduced the length of
      hospital stay in AP patients {mean difference -2.59 d (95%CI: -4.25-(-0.93)], P =
      0.002}. Although, antioxidant therapy had no significant effect on serum C
      reactive protein (CRP) after 5-7 d in AP patients [mean difference -9.57 (95%CI: 
      40.61-21.48, P = 0.55], it significantly reduced serum CRP after 10 d {mean
      difference -45.16 [95%CI: -89.99-(-0.33)], P = 0.048}. In addition, antioxidant
      therapy had no significant effect on CP-induced pain [mean difference -2.13
      (95%CI: -5.87-1.6), P = 0.26]. Antioxidant therapy had no significant effects on
      the incidence of all types of PEP [mean difference 1.05 (95%CI: 0.74-1.5), P =
      0.78], severe PEP [mean difference 0.92 (95%CI: 0.43-1.97), P = 0.83], moderate
      PEP [mean difference 0.82 (95%CI: 0.54-1.23), P = 0.33], and mild PEP [mean
      difference 1.33 (95%CI: 0.99-1.78), P = 0.06]. Furthermore, while antioxidant
      therapy had no significant effect on serum amylase after less than 8 h sampling
      [mean difference -20.61 (95%CI: -143.61-102.39), P = 0.74], it significantly
      reduced serum amylase close to 24-h sampling {mean difference -16.13 [95%CI: 
      22.98-(-9.28)], P < 0.0001}. CONCLUSION: While there is some evidence to support
      antioxidant therapy in AP, its effect on CP and PEP is still controversial.

PMID- 26290648
TI  - Enhanced recovery after surgery programs in patients undergoing hepatectomy: A
      meta-analysis.
AB  - AIM: To evaluate the impact of enhanced recovery after surgery (ERAS) programs in
      comparison with traditional care on liver surgery outcomes. METHODS: The PubMed,
      EMBASE, CNKI and Cochrane Central Register of Controlled Trials databases were
      searched for randomized controlled trials (RCTs) comparing the ERAS program with
      traditional care in patients undergoing liver surgery. Studies selected for the
      meta-analysis met all of the following inclusion criteria: (1) evaluation of ERAS
      in comparison to traditional care in adult patients undergoing elective open or
      laparoscopic liver surgery; (2) outcome measures including complications,
      recovery of bowel function, and hospital length of stay; and (3) RCTs. The
      following exclusion criteria were applied: (1) the study was not an RCT; (2) the
      study did not compare ERAS with traditional care; (3) the study reported on
      emergency, non-elective or transplantation surgery; and (4) the study consisted
      of unpublished studies with only the abstract presented at a national or
      international meeting. The primary outcomes were complications. Secondary
      outcomes were length of hospital stay and time to first flatus. RESULTS: Five
      RCTs containing 723 patients were included in the meta-analysis. In 10/723 cases,
      patients presented with benign diseases, while the remaining 713 cases had liver
      cancer. Of the five studies, three were published in English and two were
      published in Chinese. Three hundred and fifty-four patients were in the ERAS
      group, while 369 patients were in the traditional care group. Compared with
      traditional care, ERAS programs were associated with significantly decreased
      overall complications (RR = 0.66; 95%CI: 0.49-0.88; P = 0.005), grade I
      complications (RR = 0.51; 95%CI: 0.33-0.79; P = 0.003), and hospital length of
      stay [WMD = -2.77 d, 95%CI: -3.87-(-1.66); P < 0.00001]. Similarly, ERAS programs
      were associated with decreased time to first flatus [WMD = -19.69 h, 95%CI: 
      34.63-(-4.74); P < 0.0001]. There was no statistically significant difference in
      grade II-V complications between the two groups. CONCLUSION: ERAS is a safe and
      effective program in liver surgery. Future studies should define the active
      elements to optimize postoperative outcomes for liver surgery.

PMID- 26290649
TI  - Esophageal stenosis with sloughing esophagitis: A curious manifestation of graft
      vs-host disease.
AB  - We report a case of a 56-year-old woman with a history of allogenic bone marrow
      transplantation for two years, complaining with dysphagia and weight loss. Upper
      endoscopy revealed esophageal stenosis and extensive mucosa sloughing. Biopsies
      confirmed the diagnosis of graft-vs-host disease (GVHD). Balloon dilation,
      corticosteroids and cyclosporin resulted in marked clinical improvement.
      Gastrointestinal tract is involved in the majority of patients with chronic GVHD.
      Esophageal manifestations are rare and include vesiculobullous disease,
      ulceration, esophageal webs, casts or strictures. Sloughing esophagitis along
      with severe stenosis requiring endoscopic dilation has never been reported in
      this context. 

PMID- 26290650
TI  - Esophageal intramural pseudodiverticulosis of the residual esophagus after
      esophagectomy for esophageal cancer.
AB  - A 91-year-old man was referred to our hospital with intermittent dysphagia. He
      had undergone esophagectomy for esophageal cancer (T3N2M0 Stage III) 11 years
      earlier. Endoscopic examination revealed an anastomotic stricture; signs of
      inflammation, including redness, erosion, edema, bleeding, friability, and
      exudate with white plaques; and multiple depressions in the residual esophagus.
      Radiographical examination revealed numerous fine, gastrografin-filled
      projections and an anastomotic stricture. Biopsy specimens from the area of the
      anastomotic stricture revealed inflammatory changes without signs of malignancy.
      Candida glabrata was detected with a culture test of the biopsy specimens. The
      stricture was diagnosed as a benign stricture that was caused by esophageal
      intramural pseudodiverticulosis. Accordingly, endoscopic balloon dilatation was
      performed and anti-fungal therapy was started in the hospital. Seven weeks later,
      endoscopic examination revealed improvement in the mucosal inflammation; only the
      pseudodiverticulosis remained. Consequently, the patient was discharged. At the
      latest follow-up, the patient was symptom-free and the pseudodiverticulosis
      remained in the residual esophagus without any signs of stricture or
      inflammation. 

PMID- 26290651
TI  - Rare case of adult pancreatic hemangioma and review of the literature.
AB  - Pancreatic hemangiomas are a rare type of cystic tumor, with very few cases
      reported in the literature. Herein, we present the case of a 28-year-old woman
      who was admitted to our hospital for abdominal pain. A physical examination
      failed to reveal any abnormalities that could explain her symptoms. A contrast
      enhanced computed tomography showed a multilocular cyst with moderately enhanced
      septa and fluid-fluid levels in the body and tail of the pancreas. A serous
      cystadenoma or pseudocyst of the pancreas was initially suspected, and the
      patient underwent a subtotal pancreatectomy and splenectomy. The pathologic
      diagnosis was a pancreatic hemangioma. This is the second case of pancreatic
      hemangioma with fluid-fluid levels reported in the literature. Upon imaging, the
      presentation of this tumor can resemble serous or mucinous cystadenomas,
      pseudocysts of the pancreas, and side-branch type intraductal papillary mucinous
      neoplasms. This report reviews the clinical symptoms, radiologic features,
      pathologic characteristics, differential diagnoses, and treatment of this rare
      lesion type. 

PMID- 26290652
TI  - REGRESSION ANALYSIS OF CASE II INTERVAL-CENSORED FAILURE TIME DATA WITH THE
      ADDITIVE HAZARDS MODEL.
AB  - Interval-censored failure time data often arise in clinical trials and medical
      follow-up studies, and a few methods have been proposed for their regression
      analysis using various regression models (Finkelstein (1986); Huang (1996); Lin,
      Oakes, and Ying (1998); Sun (2006)). This paper proposes an estimating equation
      based approach for regression analysis of interval-censored failure time data
      with the additive hazards model. The proposed approach is robust and applies to
      both noninformative and informative censoring cases. A major advantage of the
      proposed method is that it does not involve estimation of any baseline hazard
      function. The implementation of the propsoed approach is easy and fast.
      Asymptotic properties of the proposed estimates are established and some
      simulation results and an application are provided.

PMID- 26290654
TI  - Materiality, Technology, and Constructing Social Knowledge through Bodily
      Representation: A View from Prehistoric Guernsey, Channel Islands.
AB  - The role of the human body in the creation of social knowledge-as an ontological
      and/or aesthetic category-has been applied across social theory. In all these
      approaches, the body is viewed as a locus for experience and knowledge. If the
      body is a source of subjective knowledge, then it can also become an important
      means of creating ontological categories of self and society. The materiality of
      human representations within art traditions, then, can be interpreted as
      providing a means for contextualizing and aestheticizing the body in order to
      produce a symbolic and structural knowledge category. This paper explores the
      effect of material choices and techniques of production when representing the
      human body on how societies order and categorize the world.

PMID- 26290653
TI  - Contrasting the effects of environment, dispersal and biotic interactions to
      explain the distribution of invasive plants in alpine communities.
AB  - Despite considerable efforts devoted to investigate the community assembly
      processes driving plant invasions, few general conclusions have been drawn so
      far. Three main processes, generally acting as successive filters, are thought to
      be of prime importance. The invader has to disperse (1st filter) into a suitable
      environment (2nd filter) and succeed in establishing in recipient communities
      through competitive interactions (3rd filter) using two strategies: competition
      avoidance by the use of different resources (resource opportunity), or
      competitive exclusion of native species. Surprisingly, despite the general
      consensus on the importance of investigating these three processes and their
      interplay, they are usually studied independently. Here we aim to analyse these
      three filters together, by including them all: abiotic environment, dispersal and
      biotic interactions, into models of invasive species distributions. We first
      propose a suite of indices (based on species functional dissimilarities) supposed
      to reflect the two competitive strategies (resource opportunity and competition
      exclusion). Then, we use a set of generalised linear models to explain the
      distribution of seven herbaceous invaders in natural communities (using a large
      vegetation database for the French Alps containing 5,000 community-plots).
      Finally, we measure the relative importance of competitive interaction indices,
      identify the type of coexistence mechanism involved and how this varies along
      environmental gradients. Adding competition indices significantly improved
      model's performance, but neither resource opportunity nor competitive exclusion
      were common strategies among the seven species. Overall, we show that combining
      environmental, dispersal and biotic information to model invasions has excellent
      potential for improving our understanding of invader success.

PMID- 26290655
TI  - Early identification and interventions for dyslexia: a contemporary view.
AB  - This paper reviews current proposals concerning the definition of dyslexia and
      contrasts it with reading comprehension impairment. We then discuss methods for
      early identification and review evidence that teacher assessments and ratings may
      be valid screening tools. Finally, we argue that interventions should be
      theoretically motivated and evidence based. We conclude that early identification
      of children at risk of dyslexia followed by the implementation of intervention is
      a realistic aim for practitioners and policy-makers.

PMID- 26290656
TI  - The ABRF Metabolomics Research Group 2013 Study: Investigation of Spiked Compound
      Differences in a Human Plasma Matrix.
AB  - Metabolomics is an emerging field that involves qualitative and quantitative
      measurements of small molecule metabolites in a biological system. These
      measurements can be useful for developing biomarkers for diagnosis, prognosis, or
      predicting response to therapy. Currently, a wide variety of metabolomics
      approaches, including nontargeted and targeted profiling, are used across
      laboratories on a routine basis. A diverse set of analytical platforms, such as
      NMR, gas chromatography-mass spectrometry, Orbitrap mass spectrometry, and time
      of-flight-mass spectrometry, which use various chromatographic and ionization
      techniques, are used for resolution, detection, identification, and quantitation
      of metabolites from various biological matrices. However, few attempts have been
      made to standardize experimental methodologies or comparative analyses across
      different laboratories. The Metabolomics Research Group of the Association of
      Biomolecular Resource Facilities organized a "round-robin" experiment type of
      interlaboratory study, wherein human plasma samples were spiked with different
      amounts of metabolite standards in 2 groups of biologic samples (A and B). The
      goal was a study that resembles a typical metabolomics analysis. Here, we report
      our efforts and discuss challenges that create bottlenecks for the field.
      Finally, we discuss benchmarks that could be used by laboratories to compare
      their methodologies. 

PMID- 26290657
TI  - Prevalence of eating disorders in males: a review of rates reported in academic
      research and UK mass media.
AB  - Media presentations of health issues affect evaluations of personal
      susceptibility to particular illnesses and hence help-seeking behaviours. We
      examined data on prevalence of eating disorders (EDs - which are often
      characterised as 'female') among males in: scientific literature; readily
      accessible web-based information; and UK newspaper articles (published 7/12/2002
      7/12/2012). This revealed conflicting statistics. Academic papers suggest men
      comprise around 25% of community-based samples, but much lower proportions (10%
      or less) of clinic samples. Websites and newspapers present widely differing
      statistics both on prevalence overall (numbers with EDs in the UK ranged from
      60,000 to 2.7 million), and in men (generally suggesting they constituted 10-25%
      of those with EDs), rarely distinguishing between diagnosed and non-diagnosed
      samples. By 2011, newspapers were more consistent on overall numbers with EDs in
      the UK (1.6 million) and the proportion who were men (20%), drawing on one
      website as the authoritative source. Conflicting statistics may confuse men
      searching for ED (or other) health-related information, lead to underestimations
      of male susceptibility to EDs and/or reinforce inappropriate stereotypes of EDs
      as confined to adolescent girls.

PMID- 26290658
TI  - Multifunctional Dendrimer-templated Antibody Presentation on Biosensor Surfaces
      for Improved Biomarker Detection.
AB  - Dendrimers, with their well-defined globular shape and a high density of
      functional groups, are ideal nanoscale materials for templating sensor surfaces.
      This work exploits dendrimers as a versatile platform for capturing biomarkers
      with improved sensitivity and specificity. Synthesis, characterization,
      fabrication, and functional validation of the dendrimer-based assay platform are
      described. Bifunctional hydroxyl/thiol functionalized G4-polyamidoamine (PAMAM)
      dendrimer is synthesized and immobilized on to the polyethylene-glycol (PEG)
      functionalized assay plate by coupling PEG-maleimide and dendrimer thiol groups.
      Simultaneously, part of the dendrimer thiol groups are converted to hydrazide
      functionalities. The resulting dendrimer-modified surface is coupled to the
      capture antibody in the Fc region of the oxidized antibody. This preserves the
      orientation flexibility of the antigen binding region (Fv) of the antibody. To
      validate the approach, the fabricated plates are further used as a solid phase
      for developing a sandwich type ELISA to detect IL-6 and IL-1beta, important
      biomarkers for early stages of chorioamnionitis. The dendrimer-modified plate
      provides assays with significantly enhanced sensitivity, lower nonspecific
      adsorption, and a detection limit of 0.13 pg ml-1 for IL-6 luminol detection and
      1.15 pg ml-1 for IL-1beta TMB detection, which are significantly better than
      those for the traditional ELISA. The assays were validated in human serum samples
      from normal (non-pregnant) woman and pregnant women with pyelonephritis. The
      specificity and the improved sensitivity of the dendrimer-based capture strategy
      could have significant implications for the detection of a wide range of
      cytokines and biomarkers since the capture strategy could be applied to multiplex
      microbead assays, conductometric immunosensors and field effect biosensors.

PMID- 26290660
TI  - Characterizing the Input-Output Function of the Olfactory-Limbic Pathway in the
      Guinea Pig.
AB  - Nowadays the neuroscientific community is taking more and more advantage of the
      continuous interaction between engineers and computational neuroscientists in
      order to develop neuroprostheses aimed at replacing damaged brain areas with
      artificial devices. To this end, a technological effort is required to develop
      neural network models which can be fed with the recorded electrophysiological
      patterns to yield the correct brain stimulation to recover the desired functions.
      In this paper we present a machine learning approach to derive the input-output
      function of the olfactory-limbic pathway in the in vitro whole brain of guinea
      pig, less complex and more controllable than an in vivo system. We first
      experimentally characterized the neuronal pathway by delivering different sets of
      electrical stimuli from the lateral olfactory tract (LOT) and by recording the
      corresponding responses in the lateral entorhinal cortex (l-ERC). As a second
      step, we used information theory to evaluate how much information output features
      carry about the input. Finally we used the acquired data to learn the LOT-l-ERC
      "I/O function," by means of the kernel regularized least squares method, able to
      predict l-ERC responses on the basis of LOT stimulation features. Our modeling
      approach can be further exploited for brain prostheses applications. 

PMID- 26290661
TI  - A Link between the Increase in Electroencephalographic Coherence and Performance
      Improvement in Operating a Brain-Computer Interface.
AB  - We study the relationship between electroencephalographic (EEG) coherence and
      accuracy in operating a brain-computer interface (BCI). In our case, the BCI is
      controlled through motor imagery. Hence, a number of volunteers were trained
      using different training paradigms: classical visual feedback, auditory
      stimulation, and functional electrical stimulation (FES). After each training
      session, the volunteers' accuracy in operating the BCI was assessed, and the
      event-related coherence (ErCoh) was calculated for all possible combinations of
      pairs of EEG sensors. After at least four training sessions, we searched for
      significant differences in accuracy and ErCoh using one-way analysis of variance
      (ANOVA) and multiple comparison tests. Our results show that there exists a high
      correlation between an increase in ErCoh and performance improvement, and this
      effect is mainly localized in the centrofrontal and centroparietal brain regions
      for the case of our motor imagery task. This result has a direct implication with
      the development of new techniques to evaluate BCI performance and the process of
      selecting a feedback modality that better enhances the volunteer's capacity to
      operate a BCI system. 

PMID- 26290659
TI  - MRI/SPECT/Fluorescent Tri-Modal Probe for Evaluating the Homing and Therapeutic
      Efficacy of Transplanted Mesenchymal Stem Cells in a Rat Ischemic Stroke Model.
AB  - Quantitatively tracking engraftment of intracerebrally or intravenously
      transplanted stem cells and evaluating their concomitant therapeutic efficacy for
      stroke has been a challenge in the field of stem cell therapy. In this study,
      first, an MRI/SPECT/fluorescent tri-modal probe (125I-fSiO4@SPIOs) is synthesized
      for quantitatively tracking mesenchymal stem cells (MSCs) transplanted
      intracerebrally or intravenously into stroke rats, and then the therapeutic
      efficacy of MSCs delivered by both routes and the possible mechanism of the
      therapy are evaluated. It is demonstrated that (125)I-fSiO4@SPIOs have high
      efficiency for labeling MSCs without affecting their viability, differentiation,
      and proliferation capacity, and found that 35% of intracerebrally injected MSCs
      migrate along the corpus callosum to the lesion area, while 90% of intravenously
      injected MSCs remain trapped in the lung at 14 days after MSC transplantation.
      However, neurobehavioral outcomes are significantly improved in both
      transplantation groups, which are accompanied by increases of vascular
      endothelial growth factor, basic fibroblast growth factor, and tissue inhibitor
      of metalloproteinases-3 in blood, lung, and brain tissue (p < 0.05). The study
      demonstrates that 125I-fSiO4@SPIOs are robust probe for long-term tracking of
      MSCs in the treatment of ischemic brain and MSCs delivered via both routes
      improve neurobehavioral outcomes in ischemic rats.

PMID- 26290662
TI  - Lactoferrin Induces Osteoblast Growth through IGF-1R.
AB  - Objectives. To investigate the role of the IGF-1R by which lactoferrin induces
      osteoblast growth. Methods. Osteoblast received 5 d lactoferrin intervention at a
      concentration of 0.1, 1, 10, 100, and 1000 MUg/mL, and the IGF-1 and IGF-1R were
      detected using RT-PCR and western blot. The osteoblast into the control, 100
      MUg/mL lactoferrin, Neo-scramble (NS, empty vector), NS + 100 MUg/mL lactoferrin,
      shIGF-1R and shIGF-1R + 100 MUg/mL lactoferrin group. We test the apoptosis and
      proliferation and the level of PI3K and RAS in osteoblasts after 5 d
      intervention. Results. (1) 1, 10, 100, and 1000 MUg/mL lactoferrin induced the
      expression of IGF-1 mRNA and protein. 10 MUg/mL and 100 MUg/mL lactoferrin
      induced the expression of IGF-1R mRNA and protein. (2) Lactoferrin (100 MUg/mL)
      induced osteoblast proliferation while inhibiting apoptosis. Osteoblasts with
      silenced IGF-1R exhibited decreased proliferation but increased apoptosis. MMT
      staining and flow cytometry both indicated that there was no significant
      difference between the shIGF-1R group and the shIGF-1R + 100 MUg/mL lactoferrin
      group. (3) Lactoferrin (100 MUg/mL) induced PI3K and RAS phosphorylation and
      silence of IGF-1R resulted in decreased p-PI3K and p-RAS expression. Lactoferrin
      treated shIGF-1R cells showed significantly higher level of p-PI3K and p-RAS when
      compared with shIGF-1R. Conclusion. Lactoferrin induced IGF-1/IGF-1R in a
      concentration-dependent manner. Lactoferrin promoted osteoblast proliferation
      while inhibiting apoptosis through IGF-1R. Lactoferrin activated PI3K and RAS
      phosphorylation via an IGF-1R independent pathway. 

PMID- 26290663
TI  - Osteoporosis 2014.

PMID- 26290664
TI  - Addressing Inpatient Glycaemic Control with an Inpatient Glucometry Alert System.
AB  - Background. Poor inpatient glycaemic control has a prevalence exceeding 30% and
      results in increased length of stay and higher rates of hospital complications
      and inpatient mortality. The aim of this study was to improve inpatient glycaemic
      control by developing an alert system to process point-of-care blood glucose (POC
      BG) results. Methods. Microsoft Excel Macros were developed for the processing of
      daily glucometry data downloaded from the Cobas IT database. Alerts were
      generated according to ward location for any value less than 4 mmol/L
      (hypoglycaemia) or greater than 15 mmol/L (moderate-severe hyperglycaemia). The
      Diabetes Team provided a weekday consult service for patients flagged on the
      daily reports. This system was implemented for a 60-day period. Results. There
      was a statistically significant 20% reduction in the percentage of hyperglycaemic
      patient-day weighted values >15 mmol/L compared to the preimplementation period
      without a significant change in the percentage of hypoglycaemic values. The time
      to-next-reading after a dysglycaemic POC-BG result was reduced by 14% and the
      time-to-normalization of a dysglycaemic result was reduced from 10.2 hours to 8.4
      hours. Conclusion. The alert system reduced the percentage of hyperglycaemic
      patient-day weighted glucose values and the time-to-normalization of blood
      glucose. 

PMID- 26290665
TI  - Clinical and Microbiological Profile of Pathogens in Febrile Neutropenia in
      Hematological Malignancies: A Single Center Prospective Analysis.
AB  - Background. Febrile neutropenia is the consequence of treatment of hematological
      disorders. The first-line empirical treatment should cover the prevalent
      microorganism of the institute. The aim of study was to establish the
      effectiveness of current practices used at the institution and to review the
      culture sensitivity pattern of isolated microorganisms. Patients and Methods.
      Data was recorded and analyzed prospectively for 226 hospitalized patients of
      febrile neutropenia from January 2011 till December 2013. Results. Out of 226
      cases, 173 were males and 53 were females. Clinically documented infections were
      104 (46.01%) and microbiologically documented infections were 80 (35.39%), while
      42 (18.58%) had pyrexia of undetermined origin. Gram negative infections
      accounted for 68 (85%) and Escherichia coli was the commonest isolate. Gram
      positive microorganisms were isolated in 12 (15%) cases and most common was
      Staphylococcus aureus. First-line empirical treatment with
      piperacillin/tazobactam and amikacin showed response in 184 patients (85.9%) till
      72 hours. Conclusion. There is marked decline in infections due to Gram positive
      microorganisms; however, Gram negative infections are still of great concern and
      need further surveillance. In this study the antibiogram has shown its
      sensitivity for empirical antibiotic therapy used; hence, it supports
      continuation of the same practice. 

PMID- 26290666
TI  - Comparative Analysis of Amino Acids, Nucleosides, and Nucleobases in Thais
      clavigera from Different Distribution Regions by Using Hydrophilic Interaction
      Ultra-Performance Liquid Chromatography Coupled with Triple Quadrupole Tandem
      Mass Spectrometry.
AB  - Thais clavigera, as function food, is distributed widely along the coasts of
      China. To compare and tap its potentially nutritional and functional values,
      hydrophilic interaction ultra-performance liquid chromatography coupled with
      triplequadrupole tandem mass spectrometry (HILIC-UPLC-TQ-MS/MS) was used for
      simultaneous identification and quantification of amino acids, nucleosides, and
      nucleobases in the extracts of T. clavigera from 19 sea areas in China, and a PCA
      was further performed for comparing their content variation in different
      distribution regions. The total contents of amino acids varied from 116.74 mg/g
      to 298.58 mg/g being higher than contents of nucleosides and nucleobases that
      varied from 2.65 mg/g and 20.49 mg/g. Among the habitats, Hainan province had
      content advantages on others. By PCA, samples collected from different regions
      were classified into three groups. For specific constituents, lysine accounted
      for large part of essential amino acids; glycine and taurine also play important
      roles in the delicate taste and health care function of it. Inosine takes up most
      of total contents of nucleosides and nucleobases. These results provided good
      data for establishing quality standard of T. clavigera related products and their
      further development and utilization. 

PMID- 26290667
TI  - Papillary Thyroid Cancer and Lung Adenocarcinoma Presenting as Two Primary
      Malignancies in a Patient with Symptomatic Goiter.
AB  - In rare instances, patients may be diagnosed with two different primary
      malignancies. Though such synchronous malignancies have been documented in
      sporadic case reports, the overwhelming majority of malignancies involving
      multiple organs can be attributed to a primary source. Papillary thyroid
      carcinoma and lung adenocarcinoma are rarely diagnosed within the same year. Our
      case report presents a patient who was diagnosed with these two malignancies
      during her same hospital visit. Biopsies results proved that the two malignancies
      were in fact separate entities and not a consequence of metastasis from a primary
      source. 

PMID- 26290668
TI  - Brodie's Abscess in a Patient Presenting with Sickle Cell Vasoocclusive Crisis.
AB  - First described by Sir Nicholas Brodie in 1832, Brodie's abscess is a localized
      subacute or chronic infection of the bone, typically seen in the metaphases of
      long bones in children and adolescents. The diagnosis can prove to be enigmatic
      due to absence of clinical signs and symptoms of systemic disease. We report a
      very interesting case of Brodie's abscess masquerading as sickle cell
      vasoocclusive crisis in a 20-year-old female with sickle cell disease and review
      the literature. 

PMID- 26290669
TI  - Walking with Neuropathic Pain: Paradoxical Shift from Burden to Support?
AB  - Baclofen 5% cream can be used for the treatment of neuropathic pain. We describe
      an unusual case of a neuropathic pain patient with spinal cord injury. A 71-year
      old woman with a partial spinal cord injury lesion at L4 complained of tingling,
      pins and needles, and burning in her legs. She scored her pain as 6 before adding
      baclofen 5% cream to her pain medication (pregabalin 450 mg, acetaminophen 3000
      mg, and diclofenac 150 mg daily). One month later she experienced complete pain
      relief, though experienced increased difficulties in walking, leading to frequent
      falls. Her steadier walking without stumbling and falling was more important to
      her than pain reduction. Thus she decided to stop using baclofen. This unusual
      case report discusses two important issues that relate to pain medicine and
      rehabilitation in patients with painful spinal cord lesions: (1) the presence of
      wide areas of sensory loss "covered" by the presence of painful sensations and
      (2) pathological sensations that can be used and integrated in the body schema to
      create an improved spatiovisual orientation and thus mobility. Both these aspects
      have to be taken into account when treating pain and design rehabilitation
      programs. 

PMID- 26290670
TI  - Organic Compounds Detected in Deciduous Teeth: A Replication Study from Children
      with Autism in Two Samples.
AB  - Biological samples are an important part of investigating toxic exposures and
      disease outcomes. However, blood, urine, saliva, or hair can only reflect
      relatively recent exposures. Alternatively, deciduous teeth have served as a
      biomarker of early developmental exposure to heavy metals, but little has been
      done to assess organic toxic exposures such as pesticides, plastics, or
      medications. The purpose of our study was to determine if organic chemicals
      previously detected in a sample of typically developing children could be
      detected in teeth from a sample of children with autism. Eighty-three deciduous
      teeth from children with autism spectrum disorders (ASD) were chosen from our
      tooth repository. Organic compounds were assessed using liquid chromatography
      tandem mass spectrometry and gas chromatography methods. Consistent with a prior
      report from Camann et al., (2013), we have demonstrated that specific
      semivolatile organic chemicals relevant to autism etiology can be detected in
      deciduous teeth. This report provides evidence that teeth can be useful
      biomarkers of early life exposure for use in epidemiologic case-control studies
      seeking to identify differential unbiased exposures during development between
      those with and without specific disorders such as autism. 

PMID- 26290671
TI  - Fossilized bioelectric wire - the trace fossil Trichichnus.
AB  - The trace fossil Trichichnus is proposed as an indicator of fossil bioelectric
      bacterial activity at the oxic-anoxic interface zone of marine sediments. This
      fulfils the idea that such processes, commonly found in the modern realm, should
      be also present in the geological past. Trichichnus is an exceptional trace
      fossil due to its very thin diameter (mostly less than 1 mm) and common pyritic
      filling. It is ubiquitous in some fine-grained sediments, where it has been
      interpreted as a burrow formed deeper than any other trace fossils, below the
      redox boundary. Trichichnus, formerly referred to as deeply burrowed
      invertebrates, has been found as remnant of a fossilized intrasediment bacterial
      mat that is pyritized. As visualized in 3-D by means of X-ray computed
      microtomography scanner, Trichichnus forms dense filamentous fabric, which
      reflects that it is produced by modern large, mat-forming, sulfide-oxidizing
      bacteria, belonging mostly to Thioploca-related taxa, which are able to house a
      complex bacterial consortium. Several stages of Trichichnus formation, including
      filamentous, bacterial mat and its pyritization, are proposed to explain an
      electron exchange between oxic and suboxic/anoxic layers in the sediment.
      Therefore, Trichichnus can be considered a fossilized "electric wire".

PMID- 26290673
TI  - Huqi San-Evoked Rat Colonic Anion Secretion through Increasing CFTR Expression.
AB  - Huqi San (HQS) is a Chinese herbal preparation of eight medicinal herbs that
      promote diuresis, detoxification, blood circulation, and cholestasis. Defects in
      transporter expression and function can cause cholestasis and jaundice. However,
      the mechanism of the cholestasis underlying HQS effects, especially on the
      gastrointestinal tract ion secretion, has not been elucidated. Real-time RT-PCR
      and Western blotting were used to study the expression and localization of cystic
      fibrosis transmembrane conductance regulator (CFTR) and alpha-ENaC in rat
      alimentary tract, and then the effect of HQS on the ion transport in rat distal
      colon mucosa was investigated using the short-circuit current (I SC) technique.
      The results showed that pretreatment with HQS significantly enhanced mRNA
      transcripts and protein content of CFTR in liver and distal colon but not alpha
      ENaC in alimentary organs. HQS increases I SC and decreases the transepithelial
      resistance. Pretreatment with epithelial Na(+) channel blocker did not affect the
      I SC responses elicited by HQS, but removal of extracellular Cl(-) or
      pretreatment with Cl(-) channel or Na(+)-K(+)-2Cl(-) cotransporter blocker
      inhibited HQS-elicited I SC responses. These findings demonstrated that HQS, RA,
      and RP can stimulate Cl(-) secretion in the distal colon by increasing the mRNA
      transcripts and protein content of CFTR in liver and distal colon. 

PMID- 26290674
TI  - A Glucosamine-Specific Lectin from Green Dragon No. 8 Beans (Phaseolus vulgaris)
      Induced Apoptosis on Nasopharyngeal Carcinoma Cells.
AB  - A lectin exhibiting antiproliferative activity on tumor cell lines but devoid of
      antifungal activity has been purified from Phaseolus vulgaris cv. Green Dragon
      no. 8 seeds. The lectin was a 60 kDa dimeric protein with two 30 kDa subunits. It
      was a glucosamine-specific lectin as implied from the inhibitory effect of
      glucosamine on hemagglutinating activity of the lectin. The steps for isolation
      of the lectin involved Affi-gel blue gel (affinity gel), Mono Q (anion
      exchanger), and Superdex 75 column (size exclusion). The lectin was purified 20.8
      fold from the crude extract of the beans. The purified lectin showed
      antiproliferative activity on breast cancer MCF7 cell line and nasopharyngeal
      cancer HONE1 and CNE2 cell lines, but a low activity on normal skin fibroblast
      HSF98 cell line. The lectin was shown to induce apoptosis on HONE1 cells, as
      indicated by increased phosphatidylserine externalization and mitochondrial
      depolarization. It also blocked HONE1 cell division and kept the cells at the
      G2/M phase of the cell cycle. 

PMID- 26290675
TI  - Studies on the In Vitro Antiproliferative, Antimicrobial, Antioxidant, and
      Acetylcholinesterase Inhibition Activities Associated with Chrysanthemum
      coronarium Essential Oil.
AB  - The essential oil of the Jordanian Chrysanthemum coronarium L. (garland) was
      isolated by hydrodistillation from dried flowerheads material. The oil was
      essayed for its in vitro scavenging activity using the 1,1-diphenyl-2
      picrylhydrazyl (DPPH) method. The results demonstrate that the oil exhibits
      moderate radical scavenging activity relative to the strong antioxidant ascorbic
      acid. In addition, cholinesterase inhibitory activity of C. coronarium essential
      oil was evaluated for the first time. Applying Ellman's colorimetric method,
      interesting cholinesterase inhibitory activity, which is not dose dependent, was
      evident for the oil. Furthermore, antimicrobial activities of the oil against
      both Gram-negative and Gram-positive bacteria were evaluated. While it fails to
      inhibit Gram-negative bacteria growth, the antibacterial effects demonstrated by
      the oil were more pronounced against the Gram-positive strains. Moreover, the
      examined oil was assessed for its in vitro antiproliferative properties where it
      demonstrated variable activities towards different human cancer cell lines, of
      which the colon cancer was the most sensitive to the oil treatment. 

PMID- 26290672
TI  - The Anti-Inflammatory and Antibacterial Action of Nanocrystalline Silver and
      Manuka Honey on the Molecular Alternation of Diabetic Foot Ulcer: A Comprehensive
      Literature Review.
AB  - Honey and silver have been used since ancient times for treating wounds. Their
      widespread clinical application has attracted attention in light of the
      increasing prevalence of antibiotic-resistant bacteria. While there have been a
      number of studies exploring the anti-inflammatory and antibacterial effects of
      manuka honey and nanocrystalline silver, their advantages and limitations with
      regard to the treatment of chronic wounds remain a subject of debate. The aim of
      this paper is to examine the evidence on the use of nanocrystalline silver and
      manuka honey for treating diabetic foot ulcers through a critical and
      comprehensive review of in vitro studies, animal studies, and in vivo studies.
      The findings from the in vitro and animal studies suggest that both agents have
      effective antibacterial actions. Their anti-inflammatory action and related
      impact on wound healing are unclear. Besides, there is no evidence to suggest
      that any topical agent is more effective for use in treating diabetic foot ulcer.
      Overall, high-quality, clinical human studies supported by findings from the
      molecular science on the use of manuka honey or nanocrystalline silver are
      lacking. There is a need for rigorously designed human clinical studies on the
      subject to fill this knowledge gap and guide clinical practice. 

PMID- 26290676
TI  - The Beneficial Effect of Equisetum giganteum L. against Candida Biofilm
      Formation: New Approaches to Denture Stomatitis.
AB  - Equisetum giganteum L. (E. giganteum), Equisetaceae, commonly called "giant
      horsetail," is an endemic plant of Central and South America and is used in
      traditional medicine as diuretic and hemostatic in urinary disorders and in
      inflammatory conditions among other applications. The chemical composition of the
      extract EtOH 70% of E. giganteum has shown a clear presence of phenolic compounds
      derived from caffeic and ferulic acids and flavonoid heterosides derived from
      quercitin and kaempferol, in addition to styrylpyrones. E. giganteum, mainly at
      the highest concentrations, showed antimicrobial activity against the relevant
      microorganisms tested: Escherichia coli, Staphylococcus aureus, and Candida
      albicans. It also demonstrated antiadherent activity on C. albicans biofilms in
      an experimental model that is similar to dentures. Moreover, all concentrations
      tested showed anti-inflammatory activity. The extract did not show cytotoxicity
      in contact with human cells. These properties might qualify E. giganteum extract
      to be a promising alternative for the topic treatment and prevention of oral
      candidiasis and denture stomatitis. 

PMID- 26290679
TI  - 2aBA6. Bubbles trapped on the surface of kidney stones as a cause of the
      twinkling artifact in ultrasound imaging.
AB  - A twinkling artifact (TA) associated with urinary calculi has been described as
      rapidly changing colors on Doppler ultrasound. The purpose of this study was to
      investigate the mechanism of the TA. Doppler processing was performed on raw per
      channel radio-frequency data collected when imaging human kidney stones in
      degassed water. Suppression of twinkling by an ensemble of computer generated
      replicas of a single received signal demonstrated that the TA arises from
      variability among the acoustic signals and not from electronic signal processing.
      This variability was found to be random in nature, and its suppression by
      elevated static pressure, and its return when the pressure was released, suggests
      that the presence of surface bubbles on the stone is the mechanism of the TA.
      Submicron size bubbles are often trapped in crevices on solid objects, but the
      presence of these bubbles in vivo is unexpected. To further check this mechanism
      under conditions identical to in vivo, stone-producing porcine kidneys were
      harvested en bloc with a ligated ureter and then placed into a pressure chamber
      and imaged at elevated atmospheric pressure. The result was similar to in vitro.
      Work supported by NIH DK43881, DK092197, RFBR 11-02-01189, 12-02-00114, and NSBRI
      through NASA NCC 9-58.

PMID- 26290678
TI  - Learning to Read: What We Know and What We Need to Understand Better.
AB  - The authors review current knowledge about the cognitive processes underlying the
      early stages of word reading development. Recent findings in a variety of
      alphabetic languages converge on the conclusion that there are 3 "cognitive
      foundations" for learning to read: letter-sound knowledge, phonemic awareness,
      and rapid automatized naming skills. Deficits in each of these skills appear
      causally related to problems in learning to read, and deficits in letter-sound
      knowledge and phonemic awareness appear to be remediable by suitable teaching.
      The authors argue that this evidence has important practical implications for
      early education and for the diagnosis and treatment of children with reading
      difficulties.

PMID- 26290680
TI  - Atrial Fibrillation Associated Costs for Stroke Hospitalizations of Medicare
      Beneficiaries in the Stroke Belt of the United States.
AB  - PURPOSE: To estimate atrial fibrillation (AF)-associated costs for stroke
      hospitalizations among Medicare beneficiaries aged >=65 years in a 11-state
      region called stroke belt in the United States. METHODS: Using the 2010 Medicare
      Provider Analysis and Review File database, we analyzed costs of stroke
      hospitalizations conditional on presence of AF (n=226 289) after excluding those
      with subarachnoid hemorrhage, no information on race, or a length of stay [LOS]
      of 30 or more days. We employed regression analysis to estimate for defined
      subgroups the impact of AF on costs while controlling for major potential
      confounders. RESULTS: The average cost of all stroke hospitalizations was $27
      915. The presence of AF increased this cost by $2711 (9.4%; P<0.001). AF
      associated costs were $3159, $2610, and $2197 for patients aged 65-74, 75-84, and
      >=85 years, respectively (all P<0.001). Among hospitalization with a length of
      stay (LOS) of 14-29 days, AF increased the costs by $5888 (P<0.001). AF was not
      associated with higher costs for hospitalizations involving intracerebral
      hemorrhage. CONCLUSIONS: The costs of stroke hospitalizations are high, and they
      are even higher if the patient has AF. Further information is needed on the costs
      in patients with AF who are taking anticoagulants.

PMID- 26290677
TI  - Pharmacogenomics, human genetic diversity and the incorporation and rejection of
      color/race in Brazil.
AB  - Public funding for research on the action of drugs in countries like the United
      States requires that racial classification of research subjects should be
      considered when defining the composition of the samples as well as in data
      analysis, sometimes resulting in interpretations that Whites and Blacks differ in
      their pharmacogenetic profiles. In Brazil, pharmacogenomic results have led to
      very different interpretations when compared with those obtained in the United
      States. This is explained as deriving from the genomic heterogeneity of the
      Brazilian population. This article argues that in the evolving field of
      pharmacogenomics research in Brazil there is simultaneously both an incorporation
      and rejection of the US informed race-genes paradigm. We suggest that this must
      be understood in relation to continuities with national and transnational history
      of genetic research in Brazil, a differently situated politics of Brazilian
      public health and the ongoing valorization of miscegenation or race mixture by
      Brazilian geneticists as a resource for transnational genetic research. Our data
      derive from anthropological investigation conducted in INCA (Brazilian National
      Cancer Institute), in Rio de Janeiro, with a focus on the drug warfarin. The
      criticism of Brazilian scientists regarding the uses of racial categorization
      includes a revision of mathematical algorithms for drug dosage widely used in
      clinical procedures around the world. Our analysis reveals how the incorporation
      of ideas of racial purity and admixture, as it relates to the efficacy of drugs,
      touches on issues related to the possibility of application of pharmaceutical
      technologies on a global scale.

PMID- 26290681
TI  - LPS Induces Occludin Dysregulation in Cerebral Microvascular Endothelial Cells
      via MAPK Signaling and Augmenting MMP-2 Levels.
AB  - Disrupted blood-brain barrier (BBB) integrity contributes to cerebral edema
      during central nervous system infection. The current study explored the mechanism
      of lipopolysaccharide- (LPS-) induced dysregulation of tight junction (TJ)
      proteins. Human cerebral microvascular endothelial cells (hCMEC/D3) were exposed
      to LPS, SB203580 (p38MAPK inhibitor), or SP600125 (JNK inhibitor), and cell
      vitality was determined by MTT assay. The proteins expressions of p38MAPK, JNK,
      and TJs (occludin and zonula occludens- (ZO-) 1) were determined by western blot.
      The mRNA levels of TJ components and MMP-2 were measured with quantitative real
      time polymerase chain reaction (qRT-PCR), and MMP-2 protein levels were
      determined by enzyme-linked immunosorbent assay (ELISA). LPS, SB203580, and
      SP600125 under respective concentrations of 10, 7.69, or 0.22 ug/mL had no
      effects on cell vitality. Treatment with LPS decreased mRNA and protein levels of
      occludin and ZO-1 and enhanced p38MAPK and JNK phosphorylation and MMP-2
      expression. These effects were attenuated by pretreatment with SB203580 or
      SP600125, but not in ZO-1 expression. Both doxycycline hyclate (a total MMP
      inhibitor) and SB-3CT (a specific MMP-2 inhibitor) partially attenuated the LPS
      induced downregulation of occludin. These data suggest that MMP-2 overexpression
      and p38MAPK/JNK pathways are involved in the LPS-mediated alterations of occludin
      in hCMEC/D3; however, ZO-1 levels are not influenced by p38MAPK/JNK.

PMID- 26290682
TI  - Effects of Ezetimibe/Simvastatin and Rosuvastatin on Oxidative Stress in Diabetic
      Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.
AB  - OBJECTIVE: To evaluate the effects of ezetimibe/simvastatin (EZE/SIMV) and
      rosuvastatin (ROSUV) on oxidative stress (OS) markers in patients with diabetic
      polyneuropathy (DPN). METHODS: We performed a randomized, double-blind, placebo
      controlled phase III clinical trial in adult patients with Type 2 Diabetes
      Mellitus (T2DM) and DPN, as evaluated by composite scores and nerve conduction
      studies (NCS). Seventy-four subjects with T2DM were allocated 1 : 1 : 1 to
      placebo, EZE/SIMV 10/20 mg, or ROSUV 20 mg for 16 weeks. All patients were
      assessed before and after treatment: primary outcomes were lipid peroxidation
      (LPO), and nitric oxide (NO) surrogate levels in plasma; secondary outcomes
      included NCS, neuropathic symptom scores, and metabolic parameters. Data were
      expressed as mean +/- SD or SEM, frequencies, and percentages; we used
      nonparametric analysis. RESULTS: LPO levels were reduced in both statin arms
      after 16 weeks of treatment (p < 0.05 versus baseline), without changes in the
      placebo group. NO levels were not significantly affected by statin treatment,
      although a trend towards significance concerning increased NO levels was noted in
      both statin arms. No significant changes were observed for the NCS or composite
      scores. DISCUSSION: EZE/SIMV and ROSUV are superior to placebo in reducing LPO in
      subjects with T2DM suffering from polyneuropathy. This trial is registered with
      NCT02129231.

PMID- 26290683
TI  - Characterization of Fibrin and Collagen Gels for Engineering Wound Healing
      Models.
AB  - Hydrogels are used for 3D in vitro assays and tissue engineering and regeneration
      purposes. For a thorough interpretation of this technology, an integral
      biomechanical characterization of the materials is required. In this work, we
      characterize the mechanical and functional behavior of two specific hydrogels
      that play critical roles in wound healing, collagen and fibrin. A coherent and
      complementary characterization was performed using a generalized and standard
      composition of each hydrogel and a combination of techniques. Microstructural
      analysis was performed by scanning electron microscopy and confocal reflection
      imaging. Permeability was measured using a microfluidic-based experimental set
      up, and mechanical responses were analyzed by rheology. We measured a pore size
      of 2.84 and 1.69 MUm for collagen and fibrin, respectively. Correspondingly, the
      permeability of the gels was 1.00.10-12 and 5.73.10-13 m2. The shear modulus in
      the linear viscoelastic regime was 15 Pa for collagen and 300 Pa for fibrin. The
      gels exhibited strain-hardening behavior at ca. 10% and 50% strain for fibrin and
      collagen, respectively. This consistent biomechanical characterization provides a
      detailed and robust starting point for different 3D in vitro bioapplications,
      such as collagen and/or fibrin gels. These features may have major implications
      for 3D cellular behavior by inducing divergent microenvironmental cues.

PMID- 26290684
TI  - Tracking morphologies at the nanoscale: self-assembly of an amphiphilic designer
      peptide into a double helix superstructure.
AB  - Hierarchical self-assembly is a fundamental principle in nature, which gives rise
      to astonishing supramolecular architectures that offer an inspiration for the
      development of innovative materials in nanotechnology. Here we present the unique
      structure of a cone-shaped amphiphilic designer peptide. When tracking its
      concentration-dependent morphologies, we observed elongated bilayered single
      tapes at the beginning of the assembly process, which further developed into
      novel double-helix-like superstructures at increased concentrations. This
      architecture is characterized by a tight intertwisting of two individual helices,
      resulting in a periodic pitch size over their total lengths of several hundred
      nanometers. Solution X-ray scattering data revealed a marked 2-layered internal
      organization. All these characteristics remained unaltered for the investigated
      period of almost three months. In their collective morphology the assemblies are
      integrated into a network with hydrogel characteristics. Such a peptide based
      structure holds promise for a building block of next-generation nanostructured
      biomaterials.

PMID- 26290685
TI  - Evaluating the Effect of Copper Nanoparticles in Inhibiting Pseudomonas
      aeruginosa and Listeria monocytogenes Biofilm Formation.
AB  - BACKGROUND: Biofilm formation is a major virulence factor in different bacteria.
      Biofilms allow bacteria to resist treatment with antibacterial agents. The
      biofilm formation on glass and steel surfaces, which are extremely useful
      surfaces in food industries and medical devices, has always had an important role
      in the distribution and transmission of infectious diseases. OBJECTIVES: In this
      study, the effect of coating glass and steel surfaces by copper nanoparticles
      (CuNPs) in inhibiting the biofilm formation by Listeria monocytogenes and
      Pseudomonas aeruginosa was examined. MATERIALS AND METHODS: The minimal
      inhibitory concentrations (MICs) of synthesized CuNPs were measured against L.
      monocytogenes and P. aeruginosa by using the broth-dilution method. The cell
      surface hydrophobicity of the selected bacteria was assessed using the bacterial
      adhesion to hydrocarbon (BATH) method. Also, the effect of the CuNP-coated
      surfaces on the biofilm formation of the selected bacteria was calculated via the
      surface assay. RESULTS: The MICs for the CuNPs according to the broth-dilution
      method were <= 16 mg/L for L. monocytogenes and <= 32 mg/L for P. aeruginosa. The
      hydrophobicity of P. aeruginosa and L. monocytogenes was calculated as 74% and
      67%, respectively. The results for the surface assay showed a significant
      decrease in bacterial attachment and colonization on the CuNP-covered surfaces.
      CONCLUSIONS: Our data demonstrated that the CuNPs inhibited bacterial growth and
      that the CuNP-coated surfaces decreased the microbial count and the microbial
      biofilm formation. Such CuNP-coated surfaces can be used in medical devices and
      food industries, although further studies in order to measure their level of
      toxicity would be necessary.

PMID- 26290686
TI  - Viral Load Analysis of Hepatitis C Virus in Huh7.5 Cell Culture System.
AB  - BACKGROUND: Previous studies using cell culture systems for the replication of
      hepatitis C virus have opened new research dimensions, and paved the ways for
      further and detailed studies of the virus in vitro. OBJECTIVES: The purpose of
      the present study was to cultivate hepatitis C virus in a cell culture system and
      evaluate viral amplification. MATERIALS AND METHODS: In order to propagate
      hepatitis C virus, cloned whole genome of virus, JFH-1, was used. JFH-1 cDNA was
      introduced into strain JM109 of Escherichia coli and plasmid, containing the
      viral genome was purified from transformed bacteria. After XbaI digestion, RNA
      synthesis was induced using T7 RNA polymerase enzyme. Next, eukaryotic cell line
      Huh 7.5 was transfected by the purified RNA. Finally, Huh-7.5 cell line was
      infected with replicated virus and viral load was determined using real-time PCR
      (Polymerase Chain Reaction). RESULTS: The amount of viral load, which was
      measured using real-time PCR was 17592 IU/mL. CONCLUSIONS: In the present study,
      using cell culture, a high titer (in acceptable range) of infectious hepatitis C
      virus was produced. This method could be used in future studies.

PMID- 26290687
TI  - The AT-Hook motif as a versatile minor groove anchor for promoting DNA binding of
      transcription factor fragments.
AB  - We report the development of chimeric DNA binding peptides comprising a DNA
      binding fragment of natural transcription factors (the basic region of a bZIP
      protein or a monomeric zinc finger module) and an AT-Hook peptide motif. The
      resulting peptide conjugates display high DNA affinity and excellent sequence
      selectivity. Furthermore, the AT-Hook motif also favors the cell internalization
      of the conjugates.

PMID- 26290688
TI  - Development of a heterologous enzyme-linked immunosorbent assay for
      organophosphorus pesticides with phage-borne peptide.
AB  - An enzyme-linked immunosorbent assay (ELISA) was developed to detect
      organophosphorus pesticides using a phage-borne peptide that was isolated from a
      cyclic 8-residue peptide phage library. The IC50 values of the phage ELISA ranged
      from 1.4 to 92.1 MUg L-1 for eight organophosphorus pesticides (parathion-methyl,
      parathion, fenitrothion, cyanophos, EPN, paraoxon-methyl, paraoxon, fenitrooxon).
      The sensitivity was improved 120- and 2-fold compared to conventional homologous
      and heterologous ELISA, respectively. The selectivity of the phage ELISA was
      evaluated by measuring its cross-reactivity with 23 organophosphorus pesticides,
      among which eight were the main cross-reactants. The spike recoveries were
      between 66.1% and 101.6% for the detection of single pesticide residues of
      parathion-methyl, parathion and fenitrothion in Chinese cabbage, apple and
      greengrocery, and all of the coefficient of variation were less than or equal to
      15.9%. Moreover, the phage ELISA results were validated by gas chromatography.
      The results indicate that isolating phage-borne peptides from phage display
      libraries is an alternative method for the development of a heterologous
      immunoassay and that the developed assay has a lower limit of detection than the
      chemically synthesized competitor assay.

PMID- 26290690
TI  - A new era for the Journal of Animal Science and Technology.
AB  - We anticipate that this new alliance between The Korean Society of Animal Science
      and Technology and BioMed Central will elevate our journal one step higher, and
      facilitate easier access for those overseas as well as domestic researchers, who
      in turn will support us to contribute updated research outcomes in this field. We
      cordially invite all of you to participate and submit the results of your
      research so that everyone can learn and strive towards the goals that we all
      share. 

PMID- 26290689
TI  - Alcohol consumption and risk of incident heart failure in older men: a
      prospective cohort study.
AB  - AIMS: Light-to-moderate drinking has been associated with reduced risk of heart
      failure (HF). We have examined the association between alcohol consumption and
      incident HF in older British men. METHODS AND RESULTS: Prospective study of 3530
      men aged 60-79 years with no diagnosed HF or myocardial infarction (MI) at
      baseline and followed up for a mean period of 11 years, in whom there were 198
      incident HF cases. Men were divided into 6 categories of alcohol consumption:
      none, <1, 1-6, 7-13, 14-34 and >=35 drinks/week. There was no evidence that light
      to-moderate drinking is beneficial for risk of HF. Heavy drinking (>=35
      drinks/week) was associated with significantly increased risk of HF. Using the
      large group of men drinking 1-6 drinks/week as the reference group, the relative
      HRs (95% confidence interval) for HF adjusted for age, lifestyle characteristics,
      blood pressure, atrial fibrillation and renal dysfunction were 0.97 (0.59 to
      1.63), 1.39 (0.86 to 2.25), 1.00, 0.94 (0.64 to 1.43), 1.16 (0.78 to 1.71) and
      1.91 (1.02 to 3.56) for the 6 alcohol groups, respectively. The increased risk
      associated with heavy drinking was attenuated after adjustment for N-terminal pro
      brain natriuretic peptide (NT-proBNP) (HR=1.43 (0.76 to 1.69)). Stratified
      analysis showed heavy drinking was associated with increased HF risk only in
      those with ECG evidence of myocardial ischaemia. CONCLUSIONS: There was no
      evidence that light-to-moderate drinking is beneficial for the prevention of HF
      in older men without a history of an MI. Heavier drinking (>=5 drinks/day),
      however, was associated with increased risk of HF in vulnerable men with
      underlying myocardial ischaemia.

PMID- 26290691
TI  - Hanwoo cattle: origin, domestication, breeding strategies and genomic selection.
AB  - Hanwoo (Korean cattle) is the native, taurine type of cattle breed of Korea and
      its history as a draft animal dates back to 5000 Years. In earlier times Hanwoo
      was used extensively for farming, transportation. Over the period of time, Hanwoo
      has changed to be meat type cattle. Full-scale production of Hanwoo as meat-type
      cattle has occurred since 1960s with the rapid growth of the Korean economy.
      Hanwoo is one of the most economically important species in Korea as it is a
      significant source of nutrition to the Korean people. Hanwoo beef is the most
      cherished food of Korea. One of the main goals of researchers is to increase the
      meat quality, quantity and taste of the beef. In this review we describe the
      origin, domestication of Hanwoo cattle and breeding program initiated from
      1980's. Moreover the advent of technological advancement had provided us a
      platform to perform genome wide selection on economic traits and its
      implementation into traditional breeding programs. 

PMID- 26290692
TI  - Effects of Prunella vulgaris labiatae extract on specific and non-specific immune
      responses in tilapia (Oreochromis niloticus).
AB  - We examined the effects of Prunella vulgaris Labiatae (P. vulgaris L.) on
      specific and non-specific immune responses of Nile tilapia, Oreochromis
      niloticus. The optimal concentration without toxicity of P. vulgaris was
      determined to 30-40 MUg/ml in vitro and 120 MUg/100 g of fish in vivo. P.
      vulgaris significantly elicited an antibody titer compared to FCA or beta-glucan.
      beta-glucan plus P. vulgaris group synergistically enhanced antibody production.
      No significant difference in antibody production was observed between P. vulgaris
      and P. vulgaris plus beta-glucan group. A respiratory burst activity of head
      kidney (HK) leucocytes of tilapia administered with 300 or 500 MUg P. vulgaris
      was significantly (p < 0.05) enhanced compared with the PBS-injected control
      group and FCA-treated group. Maximum increase in the NBT reduction value was
      observed in 500 MUg P. vulgaris group but no significant difference was found
      between 300 and 500 MUg P. vulgaris group. The level of serum lysozyme activity
      was significantly (p < 0.05) higher in the 300 and 500 MUg P. vulgaris than 100
      MUg P. vulgaris and FCA group. The phagocytic activities of HK leucocytes from
      tilapia administered with 300 and 500 MUg P. vulgaris were significantly (p <
      0.05) higher than 100 MUg P. vulgaris and the control group. P. vulgaris was
      revealed with a good immunoadjuvant evoking the specific and non-specific immune
      responses of tilapia. 

PMID- 26290693
TI  - Carcass and body organ characteristics of broilers supplemented with dietary
      sodium and sodium salts under a phase feeding system.
AB  - The effect of sodium and sodium salts on carcass and body organ characteristics
      of broilers under a four phase feeding program were investigated. A basal diet
      (0.08% dNa with NaCl) was formulated and one of two sources of dNa (NaHCO3 and
      Na2SO4) were supplemented to obtain four different percentages of dNa (0.17,
      0.26, 0.35, and 0.44%) for each treatment. There was a linear decrease in
      dressing percentage (DP) with source * level interaction (p <= 0.001), while
      there was a linear increase in breast yield and thigh yield with increasing dNa
      supplementation (p <= 0.001). Chicks fed 0.35% NaHCO3 and 0.44% dNa Na2SO4
      supplemental salts had lower abdominal fat (p <= 0.04). Chicks that received
      increasing levels of dNa (from 0.17 to 0.44%) showed increasing gizzard weight (p
      <= 0.002) and decreasing spleen weight (p <= 0.02). When both salts were
      supplemented at 0.26% dNa, the chicks showed their lowest bursa weight (p <=
      0.001). Consequently, chicks at higher dNa showed an increase in breast and thigh
      meat yield, and increasing capacity of their digestive organ. The higher levels
      of dNa should be tested with other cations and anions to fully understand acid
      base homoeostasis. 

PMID- 26290694
TI  - Meta-analysis of factors affecting milk component yields in dairy cattle.
AB  - The objectives of this study were thus to identify most significant factors that
      determine milk component yield (MCY) using a meta-analysis and, if possible, to
      develop equations to predict MCY using variables that can be easily measured in
      the field. A literature database was constructed based on the research articles
      published in the Journal of Dairy Science from Oct., 2007 till May, 2010. The
      database consisted of a total of 442 observed means for MCY from 118 studies. The
      candidate factors that determine MCY were those which can be routinely measured
      in the field (e.g. DMI, BW, dietary forage content, chemical composition of
      diets). Using a simple linear regression, the best equations for predicting milk
      fat yield(MFY) and milk protein yield (MPY) were MFY = 0.351 (+/-0.068) + 0.038
      (+/-0.003) DMI (R(2) = 0.27), and MPY = 0.552 (+/-0.071) + 0.031 (+/-0.002) DMI -
      0.004 (+/-0.001) FpDM (%, forage as a percentage of dietary DM) (R(2) = 0.38),
      respectively. The best equation for predicting milk fat content (%) explained
      only 12% of variations in milk fat content, and none of a single variable can
      explain more than 5% of variations in milk protein content. We concluded that
      among the tested variables, DMI was the only significant factor that affects MFY
      and both DMI and FpDM significantly affect MPY. However, predictability of linear
      equations was relatively low. Further studies are needed to identify other
      variables that can predict milk component yield more accurately. 

PMID- 26290695
TI  - Identification of proteins involved in the pancreatic exocrine by exogenous
      ghrelin administration in Sprague-Dawley rats.
AB  - The aims of study were to investigate the effects of intraperitoneal (i.p.)
      infusion of ghrelin on pancreatic alpha-amylase outputs and the responses of
      pancreatic proteins to ghrelin that may relate to the pancreatic exocrine. Six
      male Sprague-Dawley rats (300 g) were randomly divided into two groups, a control
      group (C, n = 3) and a treatment group (T, 10.0MUg/kg BW, n = 3). Blood samples
      were collected from rat caudal vein once time after one hour injection. The
      concentrations of plasma ghrelin, cholecystokinin (CCK) and alfa-amylase activity
      were evaluated by enzyme immunoassay (EIA) kit. Two-dimensional gel
      electrophoresis (2-DE) analysis was conducted to separate the proteins in
      pancreas tissue. Results showed that the i.p. infusion of ghrelin at doses of
      10.0 MUg/kg body weight (BW) increased the plasma ghrelin concentrations (p =
      0.07) and elevated the plasma CCK level significantly (p < 0.05). Although there
      was no statistically significant, the alpha-amylase activity tended to increase.
      The proteomics analysis indicated that some pancreatic proteins with various
      functions were up- or down- regulated compared with control group. In conclusion,
      ghrelin may have role in the pancreatic exocrine, but the signaling pathway was
      still not clear. Therefore, much more functional studies focus on these found
      proteins are needed in the near future. 

PMID- 26290696
TI  - Effects of dietary omega-3 polyunsaturated fatty acids on growth and immune
      response of weanling pigs.
AB  - The recognition that omega-3 polyunsaturated fatty acids (n-3 PUFA) possess
      potent anti-inflammatory properties in human models has prompted studies
      investigating their efficacy for animal growth and immunity. This study examined
      the effect of feeding an n-3 PUFA-enriched diet on growth and immune response of
      weanling piglets. Newly weaned pigs (averaging 27 +/- 2 days of age and 8.1 +/-
      0.7 kg of body weight) were assigned randomly to receive a control (3% vegetable
      oil, n = 20) or n-3 PUFA-supplemented (3% marine n-3 PUFA, n = 20) diet for 28
      day after weaning. Female pigs consuming the n-3 PUFA-enriched diet were lighter
      at week 4 post-weaning than those fed the vegetable oil supplement. Weanling pigs
      gained more weight, consumed more feed and had better growth to feed ratios
      between days 14 and 28 than between days 0 and 14 post-weaning. Plasma insulin
      like growth factor I (IGF-I) decreased between days 0 (87.2 +/- 17.0 ng/mL) and
      14 (68.3 +/- 21.1 ng/mL) after weaning and then increased again by day 28 (155.2
      +/- 20.9 ng/mL). In piglets consuming the vegetable oil-enriched diet, plasma
      tumor necrosis factor alpha (TNF-alpha) increased from 37.6 +/- 14.5 to 102.9 +/-
      16.6 pg/mL between days 0 and 14 post-weaning and remained high through day 28
      (99.0 +/- 17.2 pg/mL). The TNF-alpha increase detected in the piglets fed
      vegetable oil was not observed in the piglets fed n-3 PUFA. Results indicate that
      weaning induces considerable immune stress in piglets and that this stress can be
      mitigated by dietary supplementation of n-3 PUFA. 

PMID- 26290697
TI  - Effect of time and depth of insemination on fertility of Bharat Merino sheep
      inseminated trans-cervical with frozen-thawed semen.
AB  - BACKGROUND: Artificial insemination (AI) can serve as a powerful tool to the
      sheep owners for making rapid genetic progress of their flock. The AI in sheep is
      mostly performed using fresh semen with two reasons i) lambing rate following
      trans-cervical AI with frozen semen is limited by the inability of frozen-thawed
      sperm to transit the cervix and ii) the need of circumventing the cervical
      barrier through laparoscope aided intrauterine AI. Therefore, AI with frozen
      thawed semen is not as widespread in sheep as it is in other domestic species.
      However, to get maximum benefits through the use of AI, frozen-thawed semen is a
      prerequisite because instead of high fertility, the short shelf life of fresh
      semen coupled with a limitation on the number of insemination doses achievable
      per unit time restricts the widespread use of individual sires. Therefore, in
      order to enhance lambing rate, a total of 240 trans-cervical artificial
      inseminations with frozen-thawed semen were performed in Bharat Merino ewes
      during autumn season either once in the evening (G-I, 10 h after onset of estrus,
      n = 100) or twice (G-II, 14 h and 22 h after onset of estrus, n = 140) i.e. once
      in the morning and again in the evening. RESULTS: The pregnancy rate (proportion
      of pregnant ewes confirmed by ultrasonography at day 40) and lambing rate
      (proportion of ewes lambed) were higher in G-II as compared to G-I (26.4 vs 20%
      and 19.3 vs 10%, respectively). The difference in lambing rates was statistically
      (P < 0.05) significant. The depth of insemination within cervico-uterine tract
      had no significant effect on pregnancy and lambing rates. CONCLUSIONS: The
      results indicate that lambing rate in sheep following TCAI with frozen-thawed
      semen was significantly influenced by time of inseminations. Two inseminations
      after 14 and 22 h of onset of estrus enhanced the lambing rates of Bharat Merino
      sheep as compare to single insemination after 10 h of onset of estrus. The TCAI
      technique with frozen-thawed ram semen is promising and may serve as a valuable
      tool for genetic improvement of sheep breeds. Research efforts are going on
      worldwide to overcome the poor fertility following TCAI with frozen-thawed semen.

PMID- 26290698
TI  - Effects of different physical forms of concentrate on performance, carcass
      characteristics, and economic analysis in hanwoo steers.
AB  - This study was performed to investigate the effects of different forms of
      concentrate fed to Hanwoo steers on performance, carcass characteristics, and
      economic performance. Forty-two Hanwoo steers (average age of 5.1 +/- 0.8 mo.
      with body weight of 147.05 +/- 10.85 kg) were randomly allotted into FC (animals
      fed flakes for entire experimental period) and GC (animals fed grounded
      concentrate during growing and fattening phases followed by flaked concentrate
      during finishing phase) groups for 758 d after reaching an age of 30.0 +/- 0.82
      mo. There was no difference in body weight (BW) or ADG between the treatments
      until fattening (15 ~ 22 mo.) phase. However, by finishing phase (23 ~ 30 mo.),
      the GC group (739.24 kg BW and 0.67 kg ADG) showed greater (P < 0.05) BW and ADG
      than the FC group (702.93 kg BW and 0.59 kg ADG). Steers in the GC group also
      showed greater (P < 0.05) BW and ADG than the FC group throughout the entire
      experimental period (5 ~ 30 mo.). There was no significant difference in carcass
      weight or backfat thickness between the treatments. M. Longissimus dorsi area of
      the GC group (91.00 cm(2)cm(2)) was greater (P < 0.05) than that of the FC group
      (83.59 cm(2)). Marbling score and percentage of 1(++) meat quality grade were
      14.0 and 48.0% higher in the GC group compared to the FC group. There was no
      significant difference in physicochemical characteristics, including moisture and
      crude protein levels, between the treatments. Gross income per head excluding
      operating expenses was 59.3% greater in the GC group (1,647,512 won) compared to
      the FC group (1,034,343 won). 

PMID- 26290699
TI  - Effects of citrus pulp, fish by-product and Bacillus subtilis fermentation
      biomass on growth performance, nutrient digestibility, and fecal microflora of
      weanling pigs.
AB  - An experiment was conducted to investigate the effects of dietary supplementation
      with citrus pulp, fish by-product, and Bacillus subtilis fermentation biomass on
      the growth performance, apparent total tract digestibility (ATTD) of nutrients,
      and fecal microflora of weanling pigs. A total of 180 weaned piglets (Landrace *
      Yorkshire * Duroc) were randomly allotted to three treatments on the basis of
      body weight (BW). There were six replicate pens in each treatment with 10 piglets
      per pen. Dietary treatments were corn-soybean meal-based basal diet supplemented
      with 0 (control), 2.5, and 5.0% citrus pulp, fish by-product, and B. subtilis
      fermentation biomass. The isocaloric and isoproteineous experimental diets were
      fed in mash form in two phases (d 0 ~ 14, phase I and d 15 ~ 28, phase II).
      Dietary treatments had significant linear effects on gain to feed ratio (G:F) in
      all periods, whereas significant linear effects on ATTD of dry matter (DM), gross
      energy (GE), and ash were only observed in phase I. Piglets fed diet supplemented
      with 5.0% citrus pulp, fish by-product, and B. subtilis fermentation biomass
      showed greater (p < 0.05) G:F (phase I, phase II, and overall) as well as ATTD of
      DM, GE, and ash (phase I) than pigs fed control diet. Dietary treatments also had
      significant linear effects on total anaerobic bacteria populations by d 14 and
      28. In addition, piglets fed diet supplemented with 5.0% citrus pulp, fish by
      product and B. subtilis fermentation biomass showed greater (p < 0.05) fecal
      total anaerobic bacteria populations (d 14 and 28) than pigs fed control diet.
      Dietary treatments had no significant effects (linear or quadratic) on average
      daily gain (ADG), average dial feed intake (ADFI; phase I, phase II, and
      overall), or fecal populations of Bifidobacterium spp., Clostridium spp., and
      coliforms (d 14 and 28). These results indicate that dietary supplementation with
      5.0% citrus pulp, fish by-product, and B. subtilis fermentation biomass has the
      potential to improve the feed efficiency, nutrient digestibility, and fecal
      microflora of weanling pigs. 

PMID- 26290700
TI  - Dietary Conjugated Linoleic Acid (CLA) increases milk yield without losing body
      weight in lactating sows.
AB  - This study was conducted to evaluate the effects of dietary conjugated linoleic
      acid (CLA) on the performance of lactating sows and piglets as well as the
      immunity of piglets suckling from sows fed CLA. Eighteen multiparous Duroc sows
      with an average body weight (BW) of 232.0 +/- 6.38 kg were randomly selected and
      assigned to two dietary treatments (n = 9 for each treatment), control (no CLA
      addition) and 1% CLA supplementation. For the control diet, CLA was replaced with
      soybean oil. Experimental diets were fed to sows during a 28-day lactation
      period. Litter size for each sow was standardized to nine piglets by cross
      fostering within 24 hours after birth. Sow milk and blood samples were taken from
      sows and piglets after 21 and 27 days of lactation, respectively. Loss of BW was
      significantly (p < 0.05) higher in sows fed control diet compared to sows fed CLA
      diet. Piglet weights at weaning and weight gain during suckling were
      significantly (p < 0.05) higher in sows fed CLA compared to sows fed control
      diet. Serum non-esterified fatty acid (NEFA) and urea nitrogen concentrations
      were significantly (p < 0.05) lower in sows fed CLA than in sows fed soybean oil.
      IgG concentrations of the groups supplemented with CLA increased by 49% in sow
      serum (p < 0.0001), 23% in milk (p < 0.05), and 35% in piglet serum (p < 0.05)
      compared with the control group. Sows fed CLA showed an increase of 10% in milk
      yield compared with sows fed soybean oil (p < 0.05), even though there was no
      difference in daily feed intake between the treatments. Milk fat content was
      significantly (p < 0.05) lower in sows fed CLA than in sows fed soybean oil.
      Solid-not-fat yield was significantly (p < 0.05) higher in sows supplemented with
      CLA than in sows fed control diet and also protein-to-fat ratio in milk was
      significantly (p < 0.05) higher in sows fed CLA compared with the control group.
      The results show that CLA supplementation to sows increased milk yield without
      losing BW during lactation, whereas soybean oil supplementation resulted in
      severe BW loss. 

PMID- 26290701
TI  - Changes in expression of insulin signaling pathway genes by dietary fat source in
      growing-finishing pigs.
AB  - This study investigated changes in gene expression by dietary fat source, i.e.,
      beef tallow, soybean oil, olive oil, and coconut oil (each 3% in feed), in both
      male and female growing-finishing pigs. Real-time PCR was conducted on seven
      genes (insulin receptor; INSR, insulin receptor substrate; IRS,
      phosphatidylinositol (3,4,5)-triphosphate; PIP3, 3-phosphoinositide-dependent
      protein kinase-1; PDK1, protein kinase B; Akt, forkhead box protein O1; FOXO1 and
      cGMP-inhibited 3', 5'-cyclic phosphodiesterase; PDE3) located upstream of the
      insulin signaling pathway in the longissimus dorsi muscle (LM) of pigs. The INSR,
      IRS, PIP3, and PDE3 genes showed significantly differential expression in barrow
      pigs. Expression of the PIP3 and FOXO1 genes was significantly different among
      the four dietary groups in gilt pigs. In particular, the PIP3 gene showed the
      opposite expression pattern between barrow and gilt pigs. These results show that
      dietary fat source affected patterns of gene expression according to animal
      gender. Further, the results indicate that the type of dietary fat affects
      insulin signaling-related gene expression in the LM of pigs. These results can be
      applied to livestock production by promoting the use of discriminatory feed
      supplies. 

PMID- 26290702
TI  - Evaluation of different milking practices for optimum production performance in
      Sahiwal cows.
AB  - The production performance of multiparous lactating Sahiwal cows (n = 24) was
      evaluated according to both milking frequency and method. Selected animals were
      randomly divided into four groups containing six animals each under a completely
      randomized design. Cows in groups A & B were milked by the hand milking method
      three times per day, respectively. Similarly, cows in groups C & D were milked by
      the machine milking method two and three times per day, respectively. All animals
      were maintained under uniform feeding and management conditions. Dry matter
      intake was high in animal groups milked three times per day, and it remained
      unchanged between the hand and machine milking methods. Milk yield was higher (P
      < 0.05) in cows milked three times compared to those milked twice per day, and it
      did not differ between hand and machine milking methods. Milk fat percentage was
      higher (P < 0.05) in cows milked twice per day compared to those milked three
      times using both machine and hand milking methods. The percentage of total solids
      showed a similar pattern as the fat percentage. However, percentages of protein,
      lactose, and non-fat solids in milk were not significantly different (P > 0.05)
      among the treatment groups. Collectively, the results show that milking three
      times per day instead of twice at 8-hour intervals can enhance milk yield in
      Sahiwal cows using both hand and machine milking methods. 

PMID- 26290703
TI  - Influence of ruminal degradable intake protein restriction on characteristics of
      digestion and growth performance of feedlot cattle during the late finishing
      phase.
AB  - Two trials were conducted to evaluate the influence of supplemental urea
      withdrawal on characteristics of digestion (Trial 1) and growth performance
      (Trial 2) of feedlot cattle during the last 40 days on feed. Treatments consisted
      of a steam-flaked corn-based finishing diet supplemented with urea to provide
      urea fermentation potential (UFP) of 0, 0.6, and 1.2%. In Trial 1, six Holstein
      steers (160 +/- 10 kg) with cannulas in the rumen and proximal duodenum were used
      in a replicated 3 * 3 Latin square experiment. Decreasing supplemental urea
      decreased (linear effect, P <= 0.05) ruminal OM digestion. This effect was
      mediated by decreases (linear effect, P <= 0.05) in ruminal digestibility of NDF
      and N. Passage of non-ammonia and microbial N (MN) to the small intestine
      decreased (linear effect, P = 0.04) with decreasing dietary urea level. Total
      tract digestion of OM (linear effect, P = 0.06), NDF (linear effect, P = 0.07), N
      (linear effect, P = 0.04) and dietary DE (linear effect, P = 0.05) decreased with
      decreasing urea level. Treatment effects on total tract starch digestion,
      although numerically small, likewise tended (linear effect, P = 0.11) to decrease
      with decreasing urea level. Decreased fiber digestion accounted for 51% of the
      variation in OM digestion. Ruminal pH was not affected by treatments averaging
      5.82. Decreasing urea level decreased (linear effect, P <= 0.05) ruminal N-NH and
      blood urea nitrogen. In Trial 2, 90 crossbred steers (468 kg +/- 8), were used in
      a 40 d feeding trial (5 steers/pen, 6 pens/ treatment) to evaluate treatment
      effects on final-phase growth performance. Decreasing urea level did not affect
      DMI, but decreased (linear effect, P <= 0.03) ADG, gain efficiency, and dietary
      NE. It is concluded that in addition to effects on metabolizable amino acid flow
      to the small intestine, depriving cattle of otherwise ruminally degradable N
      (RDP) during the late finishing phase may negatively impact site and extent of
      digestion of OM, depressing ADG, gain efficiency, and dietary NE. 

PMID- 26290704
TI  - A method using artificial neural networks to morphologically assess mouse
      blastocyst quality.
AB  - BACKGROUND: Morphologically classifying embryos is important for numerous
      laboratory techniques, which range from basic methods to methods for assisted
      reproduction. However, the standard method currently used for classification is
      subjective and depends on an embryologist's prior training. Thus, our work was
      aimed at developing software to classify morphological quality for blastocysts
      based on digital images. METHODS: The developed methodology is suitable for the
      assistance of the embryologist on the task of analyzing blastocysts. The software
      uses artificial neural network techniques as a machine learning technique. These
      networks analyze both visual variables extracted from an image and biological
      features for an embryo. RESULTS: After the training process the final accuracy of
      the system using this method was 95%. To aid the end-users in operating this
      system, we developed a graphical user interface that can be used to produce a
      quality assessment based on a previously trained artificial neural network.
      CONCLUSIONS: This process has a high potential for applicability because it can
      be adapted to additional species with greater economic appeal (human beings and
      cattle). Based on an objective assessment (without personal bias from the
      embryologist) and with high reproducibility between samples or different clinics
      and laboratories, this method will facilitate such classification in the future
      as an alternative practice for assessing embryo morphologies.

PMID- 26290705
TI  - Fatty acid analysis as a tool to infer the diet in Illinois river otters (Lontra
      canadensis).
AB  - Fatty acids (FA) have recently been used in several studies to infer the diet in
      a number of species. While these studies have been largely successful, most have
      dealt with predators that have a fairly specialized diet. In this paper, we used
      FA analysis as a tool to infer the diet of the nearctic river otter (Lontra
      canadensis). The river otter is an opportunistic predator known to subsist on a
      wide variety of prey including, fishes, crayfish, molluscs, reptiles and
      amphibians, among others. We analyzed the principle components of 60 FA from
      otters and 25 potential prey species in Illinois, USA. Prey species came from 4
      major taxonomic divisions: fishes, crayfish, molluscs and amphibians. Within each
      division, most, but not all, species had significantly different profiles. Using
      quantitative FA signature analysis, our results suggest that, by mass, fish
      species are the most significant component of Illinois River otters' diet (37.7
      +/- 1.0%). Molluscs ranked second (32.0 +/- 0.8%), followed by amphibians (27.3
      +/- 4.3%), and finally, crayfish (3.0 +/- 0.6%). Our analysis indicates that
      molluscs make up a larger portion of the otter diet than previously reported.
      Throughout much of the Midwest there have been numerous otter reintroduction
      efforts, many of which appear to be successful. In regions where mollusc species
      are endangered, these data are essential for management agencies to better
      understand the potential impact of otters on these species. Our analysis further
      suggests that quantitative FA signature analysis can be used to infer diet even
      when prey species are diverse, to the extent that their FA profiles differ.
      Better understanding of the otter's metabolism of FA would improve inferences of
      diet from FA analysis. 

PMID- 26290706
TI  - Assessing the association of single nucleotide polymorphisms in thyroglobulin
      gene with age of puberty in bulls.
AB  - Puberty is a stage of sexual development determined by the interaction of many
      loci and environmental factors. Identification of genes contributing to genetic
      variation in this character can assist with selection for early pubertal bulls,
      improving genetic progress in livestock breeding. Thyroid hormones play an
      important role in sexual development and spermatogenic function. The objective of
      this study was to evaluate the association between single nucleotide
      polymorphisms (SNPs) located in thyroglobulin(TG) gene with age of puberty in
      Angus bulls. Four SNPs were genotyped in 273 animals using SEQUENOM technology
      and the association between markers and puberty age was analyzed. Results showed
      a significant association (P < 0.05) between these markers and puberty age
      estimated at a sperm concentration of 50 million and a progressive motility of
      10%. This is the first report of an association of TG polymorphisms with age of
      puberty in bulls, and results suggest the importance of thyroidal regulation in
      bovine sexual development and arrival to puberty. 

PMID- 26290707
TI  - Lesser known indigenous vegetables as potential natural egg colourant in laying
      chickens.
AB  - BACKGROUND: A six-week study involving two hundred and fifty (250) Harco Black
      layer birds at point of lay was conducted to investigate the effects of potential
      natural colorant on performance and Egg quality traits. The birds were assigned
      to five (5) dietary treatments, each containing supplements either of control,
      Baobab Leaf (BL), Waterleaf (WL), Red Pepper (RP), Canthaxanthin (CTX) at 40 g/kg
      feed and 50 mg/kg feed of natural and commercial colorants, respectively.
      RESULTS: Performance records shows that there was no significant (p > 0.05)
      difference in feed intake across the supplements of Red pepper, Water leaf,
      Canthaxanthin and control diet, however, birds fed Baobab leaf treatment had a
      significantly lower (p < 0.05) feed intake value (94.07 g) when compared with
      other treatments. Body weight gain and Hen Day Production were not significant
      influenced (p > 0.05) by the dietary treatments, although laying hens fed Baobab
      leaf supplement had lowest mean HDP of 48.80%, while birds fed Red pepper and
      Water leaf supplement had an average value of 52.79%. There was no significant
      effect (p > 0.05) of colorants on egg external traits, compared with the control;
      birds fed Canthaxanthin treatment had higher mean egg weight (51.79 g), egg
      length (4.55 g), egg breadth (3.29 g); Red pepper treatment had highest mean
      shell thickness (0.29 g), however these differences were not significant (p >
      0.05). Yolk height, Albumen height, Yolk index, and Haugh unit were not
      significantly affected (p > 0.05) across treatments. Yolk width was lowest (p <
      0.05) in Baobab leaf treatment (2.54 cm); Red pepper, Water leaf and
      Canthaxanthin (2.89 cm, 2.62 cm and 2.89 cm respectively) were not significantly
      (p > 0.05) different from the control (2.73 cm). Yolk colour score was
      significantly highest (p < 0.05) in Red pepper treatment (7.50); Water leaf,
      Baobab leaf and Canthaxanthin ranged between 2.25- 3.31 on the DSM yolk colour
      fan, Control treatment had the lowest yolk colour score (p < 0.05) of 1.31.
      CONCLUSION: The study showed Red pepper as a worthy alternative to commercial
      yolk colorant. Water leaf and baobab are not good substitutes for canthaxanthin
      as a yolk colourant.

PMID- 26290708
TI  - Perception of the HACCP system operators on livestock product manufacturers.
AB  - The purpose of this study was to investigate crucial factors on HACCP system
      implementation in domestic livestock product plants, and to offer job
      satisfaction and the career prospect of HACCP system operators. The survey was
      carried out by selecting 150 HACCP system operators who implemented HACCP system.
      The respondents claimed that the most important contents in HACCP system
      operation were to assemble HACCP team (21.8%), and the second was to monitoring
      (20.0%). Documentation and recording (16.9%) and verification (11.1%) were
      followed. The respondents answered the major factor in sanitation management was
      cleaning/washing/disinfection (18.9%) and inspection (18.4%). The results showed
      that there were significant differences in the prospect of occupation in HACCP
      system operator by the gender (p < 0.015), age, livestock product facilities,
      service period, and position (p < 0.001). The respondents from HACCP system
      operator were satisfied with their job (73%) and also showed optimistic prospect
      of occupation (82%). 

PMID- 26290709
TI  - Effects of feed form and feed particle size with dietary L- threonine
      supplementation on performance, carcass characteristics and blood biochemical
      parameters of broiler chickens.
AB  - An experiment was conducted to evaluate the effect of form and particle size of
      feed supplemented with L- threonine on growth performance, carcass characteristic
      and blood biochemical parameters of broiler chickens. The experimental design was
      a 2 * 2 * 2 factorial arrangement of treatments evaluating two feed forms (pellet
      or mash), two feed particle sizes (fine or course), and two inclusion rates of
      dietary L-threonine (with or without) which adopted from 7 to 42 days of age. In
      this experiment, 360 a day old chicks in two sexes were assigned in each
      treatment and each experimental unit was included 15 chicks. Feed consumption and
      weight gain were measured weekly. At 35 days of age, blood samples were taken to
      analysis blood biochemical parameters. At the end of the experimental period, two
      birds were slaughtered in each treatment and carcass analysis was carried out.
      The results showed that the effect of feed form on body weight gain and feed
      intake in whole of experimental period was significant (P < 0.05). Broilers fed
      pelleted diets had more weight gain than the mash group. Growth performance
      parameters were not affected by feed particle size and dietary L-threonine
      supplementation in whole of experimental period (P > 0.05). The results of
      carcass analysis showed that liver and gizzard relative weights were influenced
      by feed form (P < 0.05). However, pancreas and liver relative weights were
      affected by feed particle size and dietary L-threonine supplementation,
      respectively (P < 0.05). Triglyceride and VLDL levels were affected by feed form
      and dietary L-threonine supplementation (P < 0.05). The effect of feed particle
      size on blood biochemical parameters was not significant (P > 0.05). In
      conclusion, the experimental results indicated that feed form increased feed
      consumption and weight gain in whole of experimental period (1 to 42 days of age)
      while feed particle size and dietary L-threonine had no effect on broiler
      performance. 

PMID- 26290710
TI  - Changes in physicochemical and microbiological properties of isoflavone-treated
      dry-cured sausage from sulfur-fed pork during storage.
AB  - This study was performed to investigate the physicochemical and microbiological
      properties of isoflavone-treated dry cured sausage from sulfur fed pork (0.3%)
      during storage at 15 degrees C for 45 days. Groups were divided into three
      treatments: dry-cured sausages produced with pork fed general diet as the control
      group (CON), sulfur-fed pork (SUL) and isoflavone-(0.25%) treated sulfur-fed pork
      (ISO). Moisture content in all groups decreased dramatically from 55-57% to 10
      11% during storage, whereas crude protein, crude fat, and ash content increased
      (P < 0.05). The ISO group showed excellent antioxidant effect compared to CON
      during storage. Redness and lightness of ISO was higher than that of CON during
      storage. VBN in the ISO group was significantly lower than that in the CON and
      SUL treatments during 30 and 45 days of storage (P < 0.05). A total plate count
      of ISO was significantly lower than that of CON at 45 days (P < 0.05). In this
      study, adding isoflavone to meat products indicated prevention of lipid oxidation
      and improved color stability in meat products. 

PMID- 26290711
TI  - Effects of sires with different weight gain potentials and varying planes of
      nutrition on growth of growing-finishing pigs.
AB  - The present study was performed to investigate the effects of two groups of sires
      with 'medium' and 'high' weight gain potentials (M-sires and H-sires,
      respectively) on growth of their progenies on varying planes of nutrition during
      the growing-finishing period. The ADG of the M-sires' progeny was greater (P <
      0.05) than that of the H-sires' progeny (0.51 vs. 0.47 kg) during a 26- to 29-d
      early grower phase beginning from 55 d of age, but the opposite was true (0.66
      vs. 0.72 kg) during the latter grower phase. Overall grower-phase ADG was
      greatest on the high plane of nutrition (H plane) followed by the medium (M) and
      low (L) planes (0.65, 0.61, and 0.51 kg, respectively; P < 0.05) in the M-sires'
      progeny, whereas in the H-sires' progeny, ADG was greater on the H and M planes
      vs. L plane (0.63, 0.62, and 0.54 kg, respectively). The ADG of pigs on the M or
      H plane during the grower phase and switched to the H plane thereafter (M-to-H or
      H-to-H planes) was greater than that of pigs on the L-to-L planes (0.99 vs. 0.78
      kg) during the early finisher phase in the M-sires' progeny (P < 0.01). However,
      in the H-sires' progeny, ADG of pigs on the L-to-L planes did not differ from
      that of pigs on the M-to-M or H-to-M planes (0.94 vs. 0.96 kg). Results suggest
      that the H-to-H or H-to-M planes and M-to-M or M-to-L planes are optimal for
      maximal growth of the M- and H-sires' progenies, respectively. 

PMID- 26290713
TI  - Effects of varying nursery phase-feeding programs on growth performance of pigs
      during the nursery and subsequent grow-finish phases.
AB  - The present study investigated the effects of varying durations of nursery diets
      differing in percentages of milk products on growth performance of pigs during
      the nursery phase (NP) and subsequent grow-finish phase (GFP) to find the
      feasibility of reducing the use of nursery diets containing costly milk products.
      A total of 204 21-d-old weanling female and castrated male pigs were subjected to
      one of three nursery phase feeding programs differing in durations on the NP 1
      and 2 and GFP diets containing 20%, 7%, and 0% lacrosse and 35%, 8%, and 0% dried
      whey, respectively, in 6 pens (experimental units) for 33 d: HIGH (NP 1, 2 and 3
      diets for 7, 14, and 12 d), MEDIUM (NP 2 and 3 for 14 and 19 d), and LOW (NP 2
      and 3 and GFP 1 for 7, 14, and 12 d). Subsequently, 84 randomly selected pigs [14
      pigs (replicates)/pen] were fed the GFP 1, 2 and 3 diets during d 54-96, 96-135,
      and 135-182 of age, respectively. The final body weight (BW) and average daily
      gain (ADG) of nursery pigs did not differ among the HIGH, MEDIUM, and LOW groups
      (14.8, 13.3, and 13.7 kg in BW and 273, 225, and 237 g in ADG, respectively). The
      average daily feed intake during the nursery phase was greater (p <0.01) in the
      HIGH group than in the MEDIUM and LOW groups, whereas the gain:feed ratio did not
      differ across the treatments. The BW on d 182 and ADG during d 54-182 were
      greater in the HIGH and MEDIUM groups vs. the LOW group (110.0, 107.6, and 99.6
      kg in BW, respectively; p <0.01). The backfat thickness and carcass grade at
      slaughter on d 183 did not differ across the treatments. In conclusion, the
      MEDIUM program may be inferior to the commonly used HIGH program in supporting
      nursery pig growth. Nevertheless, the former appears to be more efficient than
      the latter in production cost per market pig whereas the LOW program is thought
      to be inefficient because of its negative effect on post-nursery pig growth. 

PMID- 26290712
TI  - A whole genomic scan to detect selection signatures between Berkshire and Korean
      native pig breeds.
AB  - BACKGROUND: Scanning of the genome for selection signatures between breeds may
      play important role in understanding the underlie causes for observable
      phenotypic variations. The discovery of high density single nucleotide
      polymorphisms (SNPs) provide a useful starting point to perform genome-wide scan
      in pig populations in order to identify loci/candidate genes underlie phenotypic
      variation in pig breeds and facilitate genetic improvement programs. However,
      prior to this study genomic region under selection in commercially selected
      Berkshire and Korean native pig breeds has never been detected using high density
      SNP markers. To this end, we have genotyped 45 animals using Porcine SNP60 chip
      to detect selection signatures in the genome of the two breeds by using the F ST
      approach. RESULTS: In the comparison of Berkshire and KNP breeds using the FDIST
      approach, a total of 1108 outlier loci (3.48%) were significantly different from
      zero at 99% confidence level with 870 of the outlier SNPs displaying high level
      of genetic differentiation (F ST >=0.490). The identified candidate genes were
      involved in a wide array of biological processes and molecular functions. Results
      revealed that 19 candidate genes were enriched in phosphate metabolism (GO:
      0006796; ADCK1, ACYP1, CAMK2D, CDK13, CDK13, ERN1, GALK2, INPP1; MAK, MAP2K5,
      MAP3K1, MAPK14, P14KB, PIK3C3, PRKC1, PTPRK, RNASEL, THBS1, BRAF, VRK1). We have
      identified a set of candidate genes under selection and have known to be involved
      in growth, size and pork quality (CART, AGL, CF7L2, MAP2K5, DLK1, GLI3, CA3 and
      MC3R), ear morphology and size (HMGA2 and SOX5) stress response (ATF2, MSRB3,
      TMTC3 and SCAF8) and immune response ( HCST and RYR1). CONCLUSIONS: Some of the
      genes may be used to facilitate genetic improvement programs. Our results also
      provide insights for better understanding of the process and influence of breed
      development on the pattern of genetic variations.

PMID- 26290714
TI  - Association of genotype of POU1F1 intron 1 with carcass characteristics in
      crossbred pigs.
AB  - This study was carried out to investigate the association of POU1F1 (POU domain,
      class 1, transcription factor 1, Pit1, renamed as POU1F1) gene with backfat
      thickness (mm), carcass weight (kg), pH, and color values (L(*), a(*), b(*)) in
      crossbred pigs (Landrace x Yorkshire x Duroc). Frequency of the AA genotype indel
      was at the highest level (66.67%). Frequency of A allele (0.81) was higher than
      that of b allele (0.19). This population followed Hardy-Weinberg equilibrium.
      Carcass weights and a(*) values of the three genotypes were all significantly
      different (p < 0.05), respectively. However, backfat thickness, L(*), b(*),
      visual color, and pH of the three genotypes were not significantly different (p >
      0.05). Visual color was negatively correlated with L(*) (r = -0.521) and b(*) (r
      = -0.390) values, L(*) value was correlated with b(*) (r = 0.419) value, and a(*)
      value was positively correlated with b(*) (r = 0.612) value. These results
      indicate that the POU1F1 gene affected carcass weight and meat redness. 

PMID- 26290715
TI  - Capacitation and acrosome reaction differences of bovine, mouse and porcine
      spermatozoa in responsiveness to estrogenic compounds.
AB  - BACKGROUND: Endocrine disruptors are exogenous substance, interfere with the
      endocrine system, and disrupt hormonal functions. However, the effect of
      endocrine disruptors in different species has not yet been elucidated. Therefore,
      we investigated the possible effects of 17beta-estradiol (E2), progesterone (P4),
      genistein (GEN) and 4-tert-octylphenol (OP), on capacitation and the acrosome
      reaction in bovine, mouse, and porcine spermatozoa. In this in vitro trial,
      spermatozoa were incubated with 0.001-100 MUM of each chemical either 15 or 30
      min and then assessed capacitation status using chlortetracycline staining.
      RESULTS: E2 significantly increased capacitation and the acrosome reaction after
      30 min, while the acrosome reaction after 15 min incubation in mouse spermatozoa.
      Simultaneously, capacitation and the acrosome reaction were induced after 15 and
      30 min incubation in porcine spermatozoa, respectively. Capacitation was
      increased in porcine spermatozoa after 15 min incubation at the lowest
      concentration, while the acrosome reaction was increased in mouse spermatozoa
      after 30 min (P <0.05). E2 significantly increased the acrosome reaction in
      porcine spermatozoa, but only at the highest concentration examined (P <0.05). P4
      significantly increased the acrosome reaction in bovine and mouse spermatozoa
      treated for 15 min (P <0.05). The same treatment significantly increased
      capacitation in porcine spermatozoa (P <0.05). P4 significantly increased
      capacitation in mouse spermatozoa treated for 30 min (P <0.05). GEN significantly
      increased the acrosome reaction in porcine spermatozoa treated for 15 and 30 min
      and in mouse spermatozoa treated for 30 min (P <0.05). OP significantly increased
      the acrosome reaction in mouse spermatozoa after 15 min (P <0.05). Besides, when
      spermatozoa were incubated for 30 min, capacitation and the acrosome reaction
      were higher than 15 min incubation in E2 or GEN. Furthermore, the responsiveness
      of bovine, mouse and porcine spermatozoa to each chemical differed. CONCLUSIONS:
      In conclusion, all chemicals studied effectively increased capacitation and the
      acrosome reaction in bovine, mouse, and porcine spermatozoa. Also we found that
      both E2 and P4 were more potent than environmental estrogens in altering sperm
      function. Porcine and mouse spermatozoa were more responsive than bovine
      spermatozoa.

PMID- 26290716
TI  - Novel SNP in the coding region of the FTO gene is associated with marbling score
      in Hanwoo (Korean cattle).
AB  - The fat mass and obesity associated (FTO) gene plays an important role in the
      regulation of energy homeostasis, fat deposition and obesity. For this reason,
      the FTO gene is a physiological and functional candidate gene for carcass and
      meat quality traits in beef cattle. The objectives of this study were to identify
      SNPs in the exonic regions of FTO gene and to evaluate the association of these
      SNPs with carcass traits in Hanwoo (Korean cattle). In this study, we newly
      identified two exonic SNPs in Hanwoo population. The g.125550A > T SNP was
      located in exon 3 and the g.175675C > T SNP was located in exon 6. Genotyping of
      the two SNP markers was carried out using PCR-RFLP analysis in Hanwoo steers to
      evaluate their association with carcass traits. As a result, g.125550A > T SNP
      genotype was significantly associated with effects on marbling score. Animals
      with the AA and TT homozygous genotypes had a significantly higher marbling score
      (p < 0.001) than those with AT heterozygous genotype, and this was significant
      after Bonferroni correction of the significance threshold (p = 0.003). Dominance
      effect was also observed for the marbling score (P < 0.05) with higher marbling
      score of homozygous animals. However, no significant associations with meat
      quality traits were observed for the g.175675C > T SNP. Our results suggest that
      the exonic SNP g.125550A > T in the FTO gene may be used as a DNA marker for the
      selection of Hanwoo with higher marbling. 

PMID- 26290717
TI  - Estimation of effective population size using single-nucleotide polymorphism
      (SNP) data in Jeju horse.
AB  - This study was conducted to estimate the effective population size using SNPs
      data of 240 Jeju horses that had raced at the Jeju racing park. Of the total
      61,746 genotyped autosomal SNPs, 17,320 (28.1%) SNPs (missing genotype rate of
      >10%, minor allele frequency of <0.05 and Hardy-Weinberg equilibrium test P-value
      of <10(-6)) were excluded after quality control processes. SNPs on the X and Y
      chromosomes and genotyped individuals with missing genotype rate over 10% were
      also excluded, and finally, 44,426 (71.9%) SNPs were selected and used for the
      analysis. The measures of the LD, square of correlation coefficient (r(2))
      between SNP pairs, were calculated for each allele and the effective population
      size was determined based on r(2) measures. The polymorphism information contents
      (PIC) and expected heterozygosity (HE) were 0.27 and 0.34, respectively. In LD,
      the most rapid decline was observed over the first 1 Mb. But r(2) decreased more
      slowly with increasing distance and was constant after 2 Mb of distance and the
      decline was almost linear with log-transformed distance. The average r(2) between
      adjacent SNP pairs ranged from 0.20 to 0.31 in each chromosome and whole average
      was 0.26, while the whole average r(2) between all SNP pairs was 0.02. We
      observed an initial pattern of decreasing Ne and estimated values were closer to
      41 at 1 ~ 5 generations ago. The effective population size (41 heads) estimated
      in this study seems to be large considering Jeju horse's population size (about
      2,000 heads), but it should be interpreted with caution because of the technical
      limitations of the methods and sample size. 

PMID- 26290718
TI  - Effects of a lipid-encapsulated zinc oxide supplement on growth performance and
      intestinal morphology and digestive enzyme activities in weanling pigs.
AB  - This study compared the effects of varying lipid content and dietary
      concentration of a lipid-encapsulated (LE) ZnO product to those of native ZnO and
      thereby to find insights into optimal lipid coating and dosage of the Zn
      supplement. A total of 192 21-d-old weanling pigs were allotted to 48 pens, after
      which each six pens received a ZnO-free basal diet supplemented with 125 ppm ZnO
      (100 ppm Zn; BASAL), 2,500 ppm Zn as native ZnO (HIGH), or 100 or 200 ppm Zn as
      LE ZnO (LE-100 or LE-250) containing 8%, 10%, or 12% lipid [LE-8%, LE-10%, or LE
      12%, respectively; 2 * 3 factorial arrangement within the LE-ZnO diets (LE-ALL)]
      for 14 d. Forty pigs were killed at the end for histological and biochemical
      examinations. None of ADG, ADFI, gain:feed, and fecal consistency score differed
      between the LE-ALL and either of the BASAL and HIGH groups. Hepatic and serum Zn
      concentrations were greater (p <0.05) in the HIGH vs. LE-ALL group, but did not
      differ between LE-ALL and BASAL, between LE-100 and -250, or among LE-8%, -10%,
      and -12% groups. Villus height (VH), crypt depth (CD), and the VH:CD ratio in the
      duodenum, jejunum, and ileum did not differ between the LE-ALL and either of the
      BASAL and HIGH groups, except for a greater CD in the duodenum in the LE-ALL vs.
      HIGH group. Additionally, VH and CD in the duodenum and VH:CD in the jejunum were
      greater in the LE-250 vs. LE-100 group. Specific activities of sucrase, maltase,
      and leucine aminopeptidase in these intestinal regions and those of amylase and
      trypsin in the pancreas were not influenced by the lipid content or dietary
      concentration of LE ZnO and also did not differ between the LE-ALL and either of
      the BASAL and HIGH groups, except for a greater pancreatic amylase activity in
      the former vs. HIGH group. In conclusion, the present results indicate that the
      LE ZnO, regardless of its lipid percentage or supplementation level examined in
      this study, has no significant effect on growth performance, fecal consistency,
      or digestive enzyme activities of weanling pigs under the experimental
      conditions. 

PMID- 26290719
TI  - Effects of repeated tuberculin skin testings on immune responses in experimental
      monkeys.
AB  - Though many alternative methods to tuberculin skin testing (TST) have been
      established and evaluated in recent years, sensitivities and specificities of
      most methods could not meet the requirements of golden standards. In this study,
      we sought to identify whether repeated TSTs could affect the immune responses in
      experimental monkeys. Nine natural tuberculosis (TB) monkeys receiving repeated
      TSTs biweekly were used to demonstrate the effect on TST responsiveness. Two
      healthy monkeys were administrated with repeated TSTs to analyze the immune
      response profiling. Intrapalpebral reactions in TB infections gradually weakened
      or presented intermittent positive reactions. The leukocyte counts, cytokine
      responses, and antibody responses to all antigens except Old tuberculin (OT) and
      MPT64L showed no specific changes for TB in healthy monkeys. Positive antibody
      responses to OT and MPT64L emerged during the first half experimental period,
      which may cause by their cross-reactivity with mycobacterial species. Results
      showed that repeated TSTs had no significant effects on immune responses in
      healthy monkeys but a progressive reduction in TST responsiveness in TB
      infections. 

PMID- 26290720
TI  - Influence of 1alpha, 25-dihydroxyvitamin D3 [1, 25(OH)2D3] on the expression of
      Sox 9 and the transient receptor potential vanilloid 5/6 ion channels in equine
      articular chondrocytes.
AB  - BACKGROUND: Sox 9 is a major marker of chondrocyte differentiation. When
      chondrocytes are cultured in vitro they progressively de-differentiate and this
      is associated with a decline in Sox 9 expression. The active form of vitamin D,
      1, 25 (OH)2D3 has been shown to be protective of cartilage in both humans and
      animals. In this study equine articular chondrocytes were grown in culture and
      the effects of 1, 25 (OH)2D3 upon Sox 9 expression examined. The expression of
      the transient receptor potential vanilloid (TRPV) ion channels 5 and 6 in equine
      chondrocytes in vitro, we have previously shown, is inversely correlated with de
      differentiation. The expression of these channels in response to 1, 25 (OH)2D3
      administration was therefore also examined. RESULTS: The active form of vitamin D
      (1, 25 (OH)2D3) when administered to cultured equine chondrocytes at two
      different concentrations significantly increased the expression of Sox 9 at both.
      In contrast 1, 25 (OH)2D3 had no significant effect upon the expression of either
      TRPV 5 or 6 at either the protein or the mRNA level. CONCLUSIONS: The increased
      expression of Sox 9, in equine articular chondrocytes in vitro, in response to
      the active form of vitamin D suggests that this compound could be utilized to
      inhibit the progressive de-differentiation that is normally observed in these
      cells. It is also supportive of previous studies indicating that 1alpha, 25
      dihydroxyvitamin D3 can have a protective effect upon cartilage in animals in
      vivo. The previously observed correlation between the degree of differentiation
      and the expression levels of TRPV 5/6 had suggested that these ion channels may
      have a direct involvement in, or be modulated by, the differentiation process in
      vitro. The data in the present study do not support this.

PMID- 26290721
TI  - Development of pig welfare assessment protocol integrating animal-, environment-,
      and management-based measures.
AB  - BACKGROUND: Due to increased interest in animal welfare, there is now a need for
      a comprehensive assessment protocol to be used in intensive pig farming systems.
      There are two current welfare assessment protocols for pigs: Welfare Quality(r)
      Assessment Protocols (applicable in the Europe Union), that mostly focuses on
      animal-based measures, and the Swine Welfare Assurance Program (applicable in the
      United States), that mostly focuses on management- and environment-based
      measures. In certain cases, however, animal-based measures might not be adequate
      for properly assessing pig welfare status. Similarly, welfare assessment that
      relies only on environment- and management-based measures might not represent the
      actual welfare status of pigs. Therefore, the objective of this paper was to
      develop a new welfare protocol by integrating animal-, environment-, and
      management-based measures. The background for selection of certain welfare
      criteria and modification of the scoring systems from existing welfare assessment
      protocols are described. METHODS: The developed pig welfare assessment protocol
      consists of 17 criteria that are related to four main principles of welfare (good
      feeding, good housing, good health, and appropriate behavior). Good feeding, good
      housing, and good health were assessed using a 3-point scale: 0 (good welfare), 1
      (moderate welfare), and 2 (poor welfare). In certain cases, only a 2-point scale
      was used: 0 (certain condition is present) or 2 (certain condition is absent).
      Appropriate behavior was assessed by scan sampling of positive and negative
      social behaviors based on qualitative behavior assessment and human-animal
      relationship tests. RESULTS: Modification of the body condition score into a 3
      point scale revealed pigs with a moderate body condition (score 1). Moreover,
      additional criteria such as feed quality confirmed that farms had moderate (score
      1) or poor feed quality (score 2), especially those farms located in a high
      relative humidity region. CONCLUSIONS: The developed protocol can be utilized to
      assess welfare status in an intensive pig farming system. Although further
      improvements are still needed, this study is a first step in developing a pig
      welfare assessment protocol that combines animal-, environment-, and management
      based measures.

PMID- 26290722
TI  - Evaluating the role of vaccine to combat peste des petits ruminants outbreaks in
      endemic disease situation.
AB  - Among the main intimidation to the sheep and goat population, PPR outbreaks are
      causing huge losses especially in endemic areas. During recent times, six
      outbreaks of PPR were confirmed at semi-organized goat farms/herds in various
      regions of Punjab province and Islamabad capital territory (ICT), Pakistan. The
      disease started after introduction of new animals at these farms with no history
      of previous PPR vaccination. The clinical signs appeared affecting respiratory
      and enteric systems and spread quickly. Disease caused mortality of 10-20% and
      morbidity of 20-40% within a time period of four weeks. Morbidity and mortality
      rates were 30.38% (86/283) and 15.55% (44/283), respectively. Three treatment
      regimes were executed to demonstrate the role of vaccination during outbreak at
      these farms. First was to use only the broad spectrum antibiotics (Penicillin &
      Streptomycin and/ or Trimethoprim and Sulfadiazine) at two farms (Texilla and
      Attock). Second treatment regime was to use the same broad spectrum antibiotic
      along with extensive fluid therapy (Farms at ICT-1 and ICT-2). The third regime
      was to use of broad spectrum antibiotic plus fluid therapy along with vaccinating
      the herd against PPR during first week of outbreak (ICT-3 and ICT-4). The third
      scheme of treatment gave the better results as there was no mortality in third
      week post-outbreak. Therefore, it is suggested to give proper importance to PPR
      vaccination along with conventional symptomatic treatment when dealing the PPR
      outbreaks in endemic disease conditions. 

PMID- 26290723
TI  - Effects of by-product feed-based silage on feeding, rumination, and excretion in
      growing Hanwoo heifers.
AB  - This study investigated the effects of feeding by-product feed (BF)-based silage
      on the behavior of growing Hanwoo heifers. Twelve Hanwoo heifers (13.2 months
      old, 315 kg body weight; four heifers per pen) were assigned to three diets: a
      rice straw (RS) diet (concentrate mix and free access to RS), a RS and BF-based
      silage (RSBFS) diet (concentrate mix and free access to RS and BF-based silage),
      and a BF-based silage (BFS) diet (concentrate mix and free access to BF-based
      silage). Behavior was recorded for 5 days using camcorders. Compared to the RS
      group, the BFS group showed 21.7% higher dry matter intake, shorter feeding,
      rumination, and chewing times, as well as longer resting time (p < 0.05).
      Although all groups exhibited similar drinking, urination, and defecation
      frequencies, the BFS group exhibited higher feeding rates, rumination efficiency,
      and chewing efficiency than the RS group (p < 0.05). Compared to the BFS group,
      the RSBFS group showed higher peNDF8.0 intake (15.2% vs. 25.0% dry matter
      intake), longer feeding and sitting times, lower defecation frequency (p < 0.05),
      and similar rumination efficiency. In conclusion, complete replacement of
      conventional RS with BF-based silage reduced rumination and chewing activity in
      growing Hanwoo heifers, and BF-based silage feeding with large-particle straw is
      an effective approach in improving heifer behavior. 

PMID- 26290724
TI  - Effects of a lipid-encapsulated zinc oxide dietary supplement, on growth
      parameters and intestinal morphology in weanling pigs artificially infected with
      enterotoxigenic Escherichia coli.
AB  - The study was performed to investigate the effect of dietary supplementation of a
      lipid-encapsulated Zinc oxide on growth parameters and intestinal mucosal
      morphology piglets born to Duroc-sired Landrace * Yorkshire dams. Twenty-four 30
      day-old piglets weaned at 25 days of age were orally challenged with 5 * 10(8)
      colony forming units of enterotoxigenic Escherichia coli (ETEC) K88 and fed one
      of the four diets for 7 days: (i) a nursery basal diet containing 100-ppm ZnO
      (referred to as BASAL), (ii) BASAL supplemented with 120-ppm apramycin (referred
      to as ANTIBIO), (iii) BASAL with 2,400-ppm ZnO (referred to as HIGH), and BASAL
      containing 100-ppm lipid-encapsulated ZnO (referred to as LE). All piglets were
      killed at the end of the experiment for histological examination on the
      intestine. The results showed that the average daily gain (ADG), the villus
      height: crypt depth (CD) ratio in the ileum, and the goblet cell density of the
      villus and crypt in the duodenum, jejunum, and colon were greater in the LE-fed
      group that those of the BASAL (p < 0.05). Fecal consistency score (FCS) and the
      CD ratio in the ileum were less in the LE-fed group, compared to the BASAL-fed
      one (p < 0.05). The effects observed in the LE-fed group were almost equal to
      those of the HIGH-fed group as well as even superior to those of the ANTIBIO-fed
      group. Taken together, our results imply that dietary supplementation of 100-ppm
      lipid-encapsulated ZnO is as effective as that of 2,400-ppm ZnO for promoting
      growth diarrhea and intestinal morphology caused by ETEC infection. 

PMID- 26290726
TI  - Effects of dietary copper on organ indexes, tissular Cu, Zn and Fe deposition and
      fur quality of growing-furring male mink (Mustela vison).
AB  - The objectives of this study were to study the effects of different levels of
      dietary copper on organ indexes, tissular Cu, Zn and Fe deposition and fur
      quality of mink in the growing-furring periods. One hundred and five standard
      dark male mink were randomly assigned to seven groups with the following dietary
      treatments: basal diet with no supplemental Cu (Control); basal diet supplemented
      with either 6, 12, 24, 48, 96 and 192 mg/kg Cu from copper sulphate,
      respectively. The colour intensity scores displayed a linear trend (P = 0.057).
      The spleen Cu concentrations responded in a linear (P < 0.05) fashion with
      increasing level of Cu, but copper supplementation did not affect speen
      concentrations of Fe or Zn. Supplemental dose of Cu linearly increased (P < 0.05)
      liver Cu and Fe concentrations but did not alter (P > 0.10) liver Zn. Our results
      indicate that Cu plays an important role in the pigmentation in growing-furring
      mink, and supplemental dietary Cu in growing-furring mink improve hair colour,
      and copper has limited effects on liver mineral deposition. 

PMID- 26290725
TI  - Discrimination of the commercial Korean native chicken population using
      microsatellite markers.
AB  - BACKGROUND: Korean native chicken (KNC) is a well-known breed due to its superior
      meat taste. This breed, however, owing to a low growth rate, has a high market
      price. In order to overcome this disadvantage, the National Institute of Animal
      Science (NIAS) in Korea developed a commercial KNC breed, named Woorimatdag
      version 2 (WM2), an upgraded version of the Woorimatdag (WM1) breed and the WM2
      was created by crossing the KNC with meat type breeds. This study aims to
      discriminate between WM2 and other chicken breeds using microsatellite (MS)
      markers. METHODS: A total of 302 individuals from eight Korean chicken
      populations were examined. The genetic diversity and population structure
      analysis were investigated using Cervus, API-CALC, STRUCTURE, PowerMarker
      programs. RESULTS: Based on heterozygosity and polymorphic information content
      (PIC) values, 30 MS markers were initially selected from 150 markers. The
      identified average number of alleles (Na), expected heterozygosity, and PIC
      values for the WM2 samples were 7.17, 0.741, and 0.682, respectively.
      Additionally, the paternity of individuals was assigned with a success rate of
      greater than 99% using 12 markers, the best minimum number of markers. The 12
      selected markers contained heterozygosity and PIC values above 0.7 and
      probability of identity values around zero. Using these markers, the determined
      probability of identity (PI), PI half-sibs , and PI sibs values were 3.23E-33,
      5.03E-22, and 8.61E-08, respectively. CONCLUSIONS: WM2 is well differentiated
      with respect to other chicken breeds based on estimated genetic distances. The
      results presented here will contribute to the identification of commercial WM2
      chicken in the market.

PMID- 26290727
TI  - Establishment of a special pathogen free Chinese Wuzhishan Minipigs Colony.
AB  - To meet the increasing demands of specific pathogen free (SPF) minipigs in
      biomedical researches, 8 pregnant Chinese Wuzhishan minipigs (WZSP) sows with
      clear background were chosen to obtain SPF WZSP by hysterectomy. At 111 +/- 2
      days of the pregnancy, piglets were aseptically taken out from the sows and
      artificially suckled for 40 to 45 days in the positive isolators. Then, the
      piglets defined as F0 were transferred to barrier environment and fed with
      standard feeds. The original SPF colony was formed for breeding by selected
      piglets from F0 group of 6-8 months old. Biological characteristics of SPF WZSP
      were collected and further compared to those of conventional (CV) WZSP, including
      growth performance, reproductive performance, hematology and blood biochemistry,
      and major pathogens detection. As a result, 61 F0 piglets were obtained from 8
      candidate sows, and 55 out of them survived. After strictly selection, 35 F0
      piglets were used to form the original SPF colony, which produced 14 litters of
      SPF piglets defined as F1. Piglet survival rates, growth performance, and
      reproductive performance of SPF WZSP were similar to CV WZSP. Some hematology and
      blood biochemistry parameters showed significant differences between SPF and CV
      WZSP. Eighteen kinds of pathogens were identified to be free in F0 and F1 SPF
      colony by repeated pathogen detections. In conclusion, we established a satisfied
      SPF WZSP colony maintaining original characteristics, free of controlled
      diseases, and being proved to be a suitable laboratory animal. 

PMID- 26290728
TI  - Effect of dietary supplementation with Spirulina on the expressions of AANAT,
      ADRB3, BTG2 and FASN genes in the subcutaneous adipose and Longissimus dorsi
      muscle tissues of purebred and crossbred Australian sheep.
AB  - BACKGROUND: The demand for healthy, lean and consistent meat products containing
      low saturated fatty acid content and high quality polyunsaturated fatty acids
      (PUFA), especially long-chain (>=C20) omega-3 PUFA, has increased in recent
      times. Fat deposition is altered by both the genetic background and dietary
      supplements, and this study aimed to assess the effect of dietary Spirulina
      supplementation levels on the mRNA expression patterns of genes controlling lipid
      metabolism in the subcutaneous adipose tissue (SAT) and Longissimus dorsi (ld)
      muscle of Australian crossbred sheep. METHODS: Twenty-four weaned lambs belonging
      to four breeds under the same management conditions were maintained on ryegrass
      pasture and fed three levels of Spirulina supplement (control, low and high). In
      terms of nutrient composition, Spirulina is a nutrient-rich supplement that
      contains all essential amino acids, vitamins and minerals. It also is a rich
      source of carotenoids and fatty acids, especially gamma-linolenic acid (GLA) that
      infer health benefits. After slaughter, subcutaneous adipose tissue (SAT) and ld
      samples were subjected to mRNA extraction and reverse transcription using
      quantitative polymerase chain reaction (RT-qPCR) to assess the mRNA expression
      levels of the Aralkylamine N-acetyltransferase (AANAT), Adrenergic beta-3
      receptor (ADRB3), B-cell translocation gene 2 (BTG2) and Fatty acid synthase
      (FASN) genes, which are associated with lipid metabolism. RESULTS: Both low and
      high Spirulina supplementation levels strongly up-regulated the transcription of
      all the selected genes in both SAT and ld tissues (mostly in the subcutaneous
      adipose), but sheep breed and sex did not influence the gene expression patterns
      in these tissues. CONCLUSIONS: The evidence indicates that high Spirulina
      supplementation level resulted in a decrease in intramuscular fat content in
      Australian purebred and crossbred sheep due to the enhanced production of
      melatonin in sheep muscle tissues and strong up-regulation of mRNA expression of
      BTG2 in SAT which negatively affected fat deposition. In contrast, low Spirulina
      supplementation level strongly up-regulated the ADRB3 and FASN genes responsible
      for fat production. These findings are consistent with the observed phenotypic
      data suggesting that low Spirulina supplementation level can increase lamb
      production, with higher long-chain PUFA content.

PMID- 26290729
TI  - Validation of a simple binary scoring system for assessment of welfare measures
      of 10-day-old commercial broilers and their correlation with environmental
      parameters.
AB  - BACKGROUND: A simple binary scoring system (SBSS) was developed and used to
      assess the welfare measures of commercial broiler chickens in South Korea. We
      also correlated welfare measures with environmental parameters of broiler house.
      Our measures of welfare included lameness, hock burn (HB) and foot pad dermatitis
      (FPD), whilst environmental parameters included air temperature, relative
      humidity, air speed, light intensity, air quality (in particular carbon dioxide
      (CO2) and ammonia (NH3) concentrations) and airborne microbes. RESULTS: The
      effect of environmental parameters on welfare measures was apparent even on 10
      day-old broilers. A non-parametric correlation analysis revealed significant
      correlations between environmental parameters and welfare measures. The key
      environmental parameters were relative humidity and light intensity. The results
      indicate that there is a need for proper control of environmental conditions on
      poultry farms, which could reduce health problems and subsequently reduce disease
      and mortality. CONCLUSIONS: In conclusion, the simplicity of SBSS makes it
      preferable over more complex scoring systems and allows a farmer to more easily
      assess the welfare measures on their own farm.

PMID- 26290730
TI  - Foot-and-mouth disease: overview of motives of disease spread and efficacy of
      available vaccines.
AB  - Control and prevention of foot and mouth disease (FMD) by vaccination remains
      unsatisfactory in endemic countries. Indeed, consistent and new FMD epidemics in
      previously disease-free countries have precipitated the need for a worldwide
      control strategy. Outbreaks in vaccinated animals require that a new and safe
      vaccine be developed against foot and mouth virus (FMDV). FMDV can be eradicated
      worldwide based on previous scientific information about its spread using
      existing and modern control strategies. 

PMID- 26290731
TI  - Effect of different soybean meal type on ileal digestibility of amino acid in
      weaning pigs.
AB  - An experiment was conducted to evaluate apparent (AID) and standardized (SID)
      ileal digestibilities of crude protein (CP) and amino acids (AA) with 6 soybean
      products in weaning pigs. A total of 14 weaning barrows with an initial body
      weight of 6.54 +/- 0.34 kg were fitted with T-cannula at the distal ileum and
      allotted to 7 diets containing various soybean products. The soybean products
      used in the experiment were conventional soybean meal (CSBM), SBM fermented by
      Aspergillus oryzae GB-107 (FSBMA), SBM fermented by Bacillus subtilis PP6
      (FSBMB), UV sterilized SBM fermented by Bacillus subtilis PP6 (UVFSBMB), SBM
      containing Bacillus subtilis PP6 (PSBM), and soy protein concentrate (SPC). Six
      corn-based diets were used and each of soybean products was added. All diets
      contained 5.0 g/kg of chromic oxide as an indigestible indicator and an N-free
      diet was used to measure basal endogenous losses of CP and AAs. Ileal CP
      digestibility did not differ by different soybean products. However, SIDs of Ile,
      Phe and Val were improved in pigs fed the FSBMB, UVFSBMB and SPC diets and the
      pigs fed the FSBMA diet showed higher SIDs of Phe and Val compared with those fed
      the CSBM diet (P < 0.05). The FSBMB diet had higher SIDs in most AAs compared
      with the FSBMA diet (P < 0.05), and higher SIDs of Lys, Ala, Pro, Ser, and Tyr
      compared with PSBM diet (P < 0.05). However, there was no response of UV
      sterilization on the FSBMB in the SIDs of AAs. These results suggest that SIDs of
      AAs could be improved by the supplementation of fermented soybean products in the
      diet for weaning pigs but fermentation with Bacillus subtilis is more efficient
      in improving ileal AA digestibility than that with Aspergillus oryzae.
      Furthermore, probiotics supplementation in the CSBM and UV-sterilization of the
      FSBMB had no effects on chemical composition and ileal AA digestibility. 

PMID- 26290732
TI  - Length polymorphism in OGT between Korean native pig, Chinese Meishan, and the
      Western pig breeds.
AB  - BACKGROUND: The Korean native pig (KNP) is generally thought to have come from
      northern China to the Korean peninsula approximately 2000 years ago. KNP pigs
      were at the brink of extinction in the 1980s, since then efforts have been made
      to restore the breed by bringing together the remaining stocks in South Korea. As
      a result, KNP was registered as a breed in 2006. To find additional breed
      specific markers that are distinct among pig breeds, variations in O-linked N
      acetylglucosamine transferase (OGT) were investigated. OGT is located on
      chromosome X and catalyzes the post-translational addition of a single O-linked
      beta-N-acetylglucosamine to target proteins. FINDINGS: Length polymorphism in the
      intron 20 of OGT was identified. The intron 20 of OGT from Duroc, Landrace, and
      Yorkshire breeds was 281-bp longer than that from either KNP or Chinese Meishan
      pigs. The difference between the Western pig breeds (BB genotype) and KNP or
      Meishan pigs (AA genotype) was due to an inserted 276-bp element and the 5-bp
      ACTTG. CONCLUSIONS: The polymorphism in OGT identified in this study may be used
      as an additional marker for determining the breed of origin among Meishan and the
      Western pig breeds. The length polymorphism suggests that the locus near OGT is
      not fixed in KNP. This marker would be relevant in determining the breed of
      origin in crossbred pigs between KNP pigs with known genotypes and the Western
      pig breeds with BB genotypes, thus confirming the contribution of the X
      chromosome from each breed.

PMID- 26290733
TI  - Development and validation of a simple, sensitive enzyme immunoassay for
      quantification of androstenedione in bull plasma.
AB  - As an alternative to radioimmunoassay a simple and highly sensitive enzyme
      immunoassay (EIA) was developed and validated for androstenedione quantification
      in plasma of Karan Fries bulls using second antibody coating technique. The wells
      of the microtitreplate were coated with affinity-purified goat immunoglobulin
      (antirabbit IgG) that binds the hormone specific antibody. The EIA was performed
      to analyze androstenedione directly in 40 MUl of bull plasma. The androstenedione
      standards ranged from 0.20 to 200 pg/40 MUl /well and the sensitivity of the
      assay was 5 pg/ml plasma. Serially diluted bull plasma containing high endogenous
      androstenedione showed good parallelism with bovine androstenedione standard
      curve. Intra- and inter-assay coefficients of variation (CV) were found to be 8
      and 9%, respectively. Peripheral plasma androstenedione concentrations determined
      in young and adult bull samples ranged between 104-990 pg/ml and 184-2040 pg/ml,
      respectively. 

PMID- 26290734
TI  - Effects of forage level and chromium-methionine chelate supplementation on
      performance, carcass characteristics and blood metabolites in Korean native
      (Hanwoo) steers.
AB  - A feeding trial was carried out to determine the effects of chromium methionine
      (Cr-Met) chelate and forage level over two years, 1(st) fattening and 2(nd)
      fattening period on growth parameters, carcass characteristics and blood
      metabolites of 46 Korean native (Hanwoo, Bos Taurus, BW = 183 +/- 44 kg) steers.
      Treatments were: 1) Steers in the low forage (LF) group were fed diets that
      consisted of 60% concentrate and 40% forage; 2) Steers in the high forage (HF)
      group were fed diets that consisted of 40% concentrate and 60% forage. Following
      the 1(st) fattening period, steers (BW = 480 +/- 37.6 kg) were randomly assigned
      to four treatment groups: LF (40 F plus no Cr-Met supplementation in the 2(nd)
      fattening period), LFCM (40LF plus added 400 ppb of Cr-Met during the 2(nd)
      fattening period), HF (60 F plus no added Cr-Met during the 2(nd) fattening
      period) and HFCM (60 F plus added 400 ppb of Cr-Met in the 2(nd) fattening
      period). Dry matter intake of the treatment diets did not differ during the
      raising and 1(th) fattening period (P > 0.05). The ADG in the raising period
      showed no difference between the 40 F and 60 F groups (P > 0.05). Carcass
      characteristics including rib-eye area and meat yield index were higher in HF
      than the other treatment groups (P < 0.05). The HF group tended to show a higher
      (P = 0.08) marbling score than the LF group whereas the HFCM group showed a
      higher marbling score than the LFCM group (P < 0.05). HDL was higher and LDL
      lower in groups fed with Cr-Met than in other groups whereas glucose showed the
      lowest value in HF group (P < 0.05). Triglyceride (TG), Cholesterol, PUN and
      total protein (TP) were the same among all treatment groups (P > 0.05). The
      Insulin concentration in the blood was significantly higher for the HFCM group
      than for the LF, LFCM and HF groups (P < 0.05). It is concluded that
      supplementation of chromium-methionine chelate could improve meat quality in beef
      steers. 

PMID- 26290735
TI  - Characteristics of Gouda cheese supplemented with fruit liquors.
AB  - This study was conducted in order to evaluate the quality characteristics of
      Gouda cheeses supplemented with fruit liquor (Prunusmume or Cornus officinalis).
      Fruit liquor was supplemented to Gouda cheeses during preparation. Changes in
      chemical composition, lactic acid bacterial population, pH, water-soluble
      nitrogen, sensory characteristics, and proteolysis were monitored in the prepared
      ripened cheese. The electrophoresis patterns of cheese proteins, fruit liquor
      functional component concentrations, and the flavonoid content of the cheeses
      were also determined. The addition of fruit liquor did not affect (p> 0.05) the
      appearance or sensory characteristics of the cheeses. Higher amounts of crude
      ash, mineral, and flavonoids (p< 0.05) were observed in the liquor supplemented
      cheese than in the control cheese. Findings from this study suggest that wine
      supplemented Gouda could provide additional nutrients while maintaining flavor
      and quality. 

PMID- 26290736
TI  - Molecular cloning and characterization of Izumo1 gene from bovine testis.
AB  - A well-characterized sperm specific protein of the Member of immunoglobulin
      superfamily, IZUMO1, has crucial role in fertilization by mediating sperm binding
      to the egg plasma membrane in the mouse. However little is known about IZUMO1 in
      bovine. Here, we describe the molecular cloning and expression analysis of bovine
      IZUMO1 (bIZUMO1). RT-PCR and Western blot analysis of the bovine tissues
      indicated that bIZUMO1 was specifically expressed in the testis and sperm,
      Furthermore, the result of our biotinylation assay from ejaculated bovine sperm
      strongly suggest the assumption that bIZUMO1 is localized on the cell surface.
      These data imply the potential role of bovine IZUMO1 in mammalian fertilization. 

PMID- 26290737
TI  - Cashew reject meal in diets of laying chickens: nutritional and economic
      suitability.
AB  - The present study investigated the nutritional and economic suitability of cashew
      reject meal (full fat and defatted) as replacement for groundnut cake (GNC) in
      the diets of laying chickens. A total of eighty four brown shavers at 25 weeks of
      age were randomly allotted into seven dietary treatments each containing 6
      replicates of 2 birds each. The seven diets prepared included diet 1, a control
      with GNC at 220gkg(-1) as main protein source in the diet. Diets 2, 3 and 4
      consist of gradual replacement of GNC with defatted cashew reject meal (DCRM) at
      50%, 75% and 100% on weight for weight basis respectively while diets 5, 6 and 7
      consist of gradual inclusion of full fat cashew reject meal (FCRM) to replace
      25%, 35% and 50% of GNC protein respectively. Each group was allotted a diet in a
      completely randomized design in a study that lasted eight weeks during which
      records of the chemical constituent of the test ingredients, performance
      characteristics, egg quality traits and economic indicators were measured.
      Results showed that the crude protein were 22.10 and 35.4% for FCRM and DCRM
      respectively. Gross energy of DCRM was 5035 kcal/kg compared to GNC, 4752
      kcal/kg. Result of aflatoxin B1 revealed moderate level between 10 and 17 MUg/Kg
      in DCRM and GNC samples respectively. Birds on control gained 10 g, while those
      on DCRM and FCRM gained about 35 g and 120 g respectively. Feed intake declined
      (P < 0.05) with increased level of FCRM. Hen day production was highest in birds
      fed DCRM, followed by control and lowest value (P < 0.05) was recorded for FCRM.
      No significant change (P > 0.05) was observed for egg weight and shell thickness.
      Fat deposition and cholesterol content increased (P > 0.05) with increasing level
      of FCRM. The cost of feed per kilogram decreased gradually with increased
      inclusion level of CRM. The prediction equation showed the relative worth of DCRM
      compared to GNC was 92.3% whereas the actual market price of GNC triples that of
      DCRM. It was recommended that GNC could be completely replaced by DCRM in layer's
      diets in regions where this by product is abundant. However, FCRM should be
      cautiously used in diets of laying chickens. 

PMID- 26290738
TI  - GAPDH, beta-actin and beta2-microglobulin, as three common reference genes, are
      not reliable for gene expression studies in equine adipose- and marrow-derived
      mesenchymal stem cells.
AB  - BACKGROUND: Quantitative real time reverse transcription PCR (qRT-PCR) is one of
      the most important techniques for gene-expression analysis in molecular based
      studies. Selecting a proper internal control gene for normalizing data is a
      crucial step in gene expression analysis via this method. The expression levels
      of reference genes should be remained constant among cells in different tissues.
      However, it seems that the location of cells in different tissues might influence
      their expression. The purpose of this study was to determine whether the source
      of mesenchymal stem cells (MSCs) has any effect on expression level of three
      common reference genes (GAPDH, beta-actin and beta2-microglobulin) in equine
      marrow- and adipose- derived undifferentiated MSCs and consequently their
      reliability for comparative qRT-PCR. MATERIALS AND METHODS: Adipose tissue (AT)
      and bone marrow (BM) samples were harvested from 3 mares. MSCs were isolated and
      cultured until passage 3 (P3). Total RNA of P3 cells was extracted for cDNA
      synthesis. The generated cDNAs were analyzed by quantitative real-time PCR. The
      PCR reactions were ended with a melting curve analysis to verify the specificity
      of amplicon. RESULTS: The expression levels of GAPDH were significantly different
      between AT- and BM- derived MSCs (p < 0.05). Differences in expression level of
      beta-actin (P < 0.001) and B2M (P < 0.006.) between MSCs derived from AT and BM
      were substantially higher than GAPDH. In addition, the fold change in expression
      levels of GAPDH, beta-actin and B2M in AT-derived MSCs compared to BM-derived
      MSCs were 2.38, 6.76 and 7.76, respectively. CONCLUSION: This study demonstrated
      that GAPDH and especially beta-actin and B2M express in different levels in
      equine AT- and BM- derived MSCs. Thus they cannot be considered as reliable
      reference genes for comparative quantitative gene expression analysis in MSCs
      derived from equine bone marrow and adipose tissue.

PMID- 26290739
TI  - Estimation of genetic relationships between growth curve parameters in Guilan
      sheep.
AB  - The objective of this study was to estimate variance components and genetic
      parameters for growth curve parameters in Guilan sheep. Studied traits were
      parameters of Brody growth model which included A (asymptotic mature weight), B
      (initial animal weight) and K (maturation rate). The data set and pedigree
      information used in this study were obtained from the Agricultural Organization
      of Guilan province (Rasht, Iran) and comprised 8647 growth curve records of lambs
      from birth to 240 days of age during 1994 to 2014. Marginal posterior
      distributions of parameters and variance components were estimated using TM
      program. The Gibbs sampler was run 300000 rounds and the first 60000 rounds were
      discarded as a burn-in period. Posterior mean estimates of direct heritabilities
      for A, B and K were 0.39, 0.23 and 0.039, respectively. Estimates of direct
      genetic correlation between growth curve parameters were 0.57, 0.03 and -0.01
      between A-B, A-K and B-K, respectively. Estimates of direct genetic trends for A,
      B and K were positive and their corresponding values were 0.014 +/- 0.003 (P <
      0.001), 0.0012 +/- 0.0009 (P > 0.05) and 0.000002 +/- 0.0001 (P > 0.05),
      respectively. Residual correlations between growth curve parameters varied form 
      0.52 (between A-K) to 0.48 (between A-B). Also, phenotypic correlations between
      growth curve parameters varied form -0.49 (between A-K) to 0.47 (between A-B).
      The results of this study indicated that improvement of growth curve parameters
      of Guilan sheep seems feasible in selection programs. It is worthwhile to develop
      a selection strategy to obtain an appropriate shape of growth curve through
      changing genetically the parameters of growth model. 

PMID- 26290740
TI  - Investigation of Hanwoo manure management and estimation of nutrient loading
      coefficients on land application.
AB  - BACKGROUND: In order to prepare for the regulation about the limit of manure
      production, the status of manure management and the amount of nutrients in the
      compost discharged from Hanwoo breeding farm shall be known. This study aimed to
      find the practical amount of nutrients (volatile solids, VS; total nitrogen, T-N;
      total phosphorus, T-P) in manure, and compost samples collected from 40 Hanwoo
      breeding farms and the loss of the nutrients was calculated during the composting
      period, which supports to develop nutrient loading coefficients (NLCs) for each
      nutrient. RESULTS: Although the addition of bedding materials for composting
      caused the increase of the VS amount before composting, the comparison of VS, N,
      and P amounts in between manure and compost showed the lower VS by 4 % as well as
      T-N and T-P amounts by 69 and 40 %, respectively, of which values were
      corresponded with the NLCs of 0.96, 0.31, and 0.60 for VS, N, and P,
      respectively, based on the questionnaire, and sample analyses. Considering with
      the environmental impacts including land application from Hanwoo manure, P loss
      should be zero before and after composting. In this regard, nitrogen loss of 50 %
      occurs and VS was increased by 30 %. In addition, feasible cases for the
      calculations based on the notification from Ministry of Environment were compared
      with this study. CONCLUSIONS: The development of NLCs from Hanwoo manure in this
      study implies that the loss of nutrients in manure occurs during the composting
      or storing period. The mass balances of N and P from livestock manure to land
      application may be overestimated over the practical values. It is necessary to
      build up the database about each livestock category other than Hanwoo.

PMID- 26290741
TI  - Comparative ileal amino acid digestibility and growth performance in growing pigs
      fed different level of canola meal.
AB  - The digestibility of different vegetable protein sources were investigated and
      the effects of supplementing canola meal (CM) as partial inclusions were studied
      in growing pigs, to determine the performance parameters and its economic
      importance. In Exp. 1, four pigs (average initial BW = 15.4 +/- 0.35 kg, 5 weeks
      of age) fitted with simple T-cannula at terminal ileum, were fed four diets
      following repeated 4 * 4 Latin square design having adoption period of 7 days.
      Diet 1 was Nitrogen free diet containing corn starch. Diets 2, 3, and 4 were the
      basal diet supplemented with soybean meal (SBM), rapeseed meal (RSM), and
      domestic CM respectively. The AID of crude protein was decrease in RSM in
      comparison to SBM supplementation. The AID of Dietary indispensable amino acids
      (DIAA) such as Lys, Meth, Pha, and dispensable amino acid Ala, Pro, Asp were
      decreased (P < 0.05) in RSM supplemented diets. The SID of DIAA does not differ
      but the SID of Asp was higher (P < 0.05) in RSM and CM diets while SID of Pro was
      lower (P < 0.05) in RSM in comparison to SBM supplemented diets. In Exp. 2, 192
      growing pigs (average initial BW 24.76 +/- 2.55 kg) were randomly allotted to
      four dietary treatments with increasing levels of CM i.e. 0, 3.75, 7.50, and
      11.25 % respectively. Diets were fed in meal form for 35 days. Increasing CM
      levels in diets had no effects (P > 0.05) on growth performance and apparent
      total tract digestibility (ATTD) of nutrients and energy. Total weight gain,
      total feed intake, and feed cost per kg weight gain were not affected by
      increasing levels of CM in diets but total feed cost (TFC) per pigs was linearly
      reduced (26.463 to 25.674; P < 0.05). Broadly, the AID, and SID of amino acid was
      reduced in RSM but was not effected in CM in comparison to SBM supplemented pigs.
      Moreover, increasing levels of CM in pigs diet had no effect on the ATTD and
      performance but TFC per pig was reduced. Thus CM inclusion of up to 11.25 % in
      diets can be used for reducing the production cost in growing pigs without any
      negative effect. 

PMID- 26290742
TI  - Characteristics of pork belly consumption in South Korea and their health
      implication.
AB  - Fresh pork belly is a highly popular meat in South Korea, accounting for 59 % of
      the approximately 100 g of meat per capita that is consumed daily. Fresh pork
      belly offers not only high-quality protein from the lean cuts but also
      substantial micronutrients including fat-soluble vitamins and minerals. However,
      fresh pork belly generally consists of about 30 % fat, with saturated fatty acids
      representing half of this value. Excessive consumption of saturated fatty acids
      increases total cholesterol, low-density lipoprotein-cholesterol, and
      triglycerides while decreasing high-density lipoprotein-cholesterol, raising
      concerns about an increased risk of hyperlipidemia, followed by cardiovascular
      diseases. In this review, we discuss the consumption and production trends in
      South Korea, the general characteristics, and health issues related to fresh pork
      belly to delineate the features of pork production and consumer welfare. 

PMID- 26290743
TI  - Multifarious activities of cellulose degrading bacteria from Koala (Phascolarctos
      cinereus) faeces.
AB  - Cellulose degrading bacteria from koala faeces were isolated using
      caboxymethylcellulose-Congo red agar, screened in vitro for different hydrolytic
      enzyme activities and phylogenetically characterized using molecular tools.
      Bacillus sp. and Pseudomonas sp. were the most prominent bacteria from koala
      faeces. The isolates demonstrated good xylanase, amylase, lipase, protease,
      tannase and lignin peroxidase activities apart from endoglucanase activity.
      Furthermore many isolates grew in the presence of phenanthrene, indicating their
      probable application for bioremediation. Potential isolates can be exploited
      further for industrial enzyme production or in bioremediation of contaminated
      sites. 

PMID- 26290744
TI  - Physicochemical traits of Holstein loin and top round veal from two slaughter age
      groups.
AB  - The objective of this study was to investigate the physicochemical and microbial
      quality of loin (m. longissimus dorsi) and top round (m. Semimembranosus) in
      Holstein veal produced from two slaughter age groups (5 and 8 months of age). A
      total of 20 Holstein calves were randomly selected from a local cattle farm. The
      slaughtered cold carcasses were vacuum-packaged. The samples were analyzed for
      proximate composition and physicochemical analyses and stored for 1, 7, 10, 20
      and 30 days for microbiological analyses. Fat and protein contents of loin for
      the 8 month group were higher than those for the 5 month groups (p < 0.05). For
      both loin and top round muscles, the pH, cooking loss and the shear force values
      for the 5 month group was higher than those for the 8 month group (p < 0.05). On
      the other hands, the water-holding capacity (WHC) for the 8 month group was
      higher than those for the 5 month group (p < 0.05). In terms of meat color, CIE
      L* (lightness) for both muscle were higher in the 5 month group than in the 8
      month groups. On the other hands, a* (redness) were higher in the 8 month group
      than in the 5 month groups (p < 0.05). Total aerobic counts in all samples
      remained up to 30 days at values less than 7 log CFU/g. However, there was no
      significant difference for both muscles between the two age groups. The results
      indicate that Holstein muscles from the 8 month group had desirable quality
      properties than those from the 5 month group. 

PMID- 26290745
TI  - A comparison of supplemental calcium soap of palm fatty acids versus tallow in a
      corn-based finishing diet for feedlot steers.
AB  - Rumen bypass fat is commonly added to increase energy intake in dairy cattle. The
      objective of this study is to examine the addition of rumen bypass fat during
      finishing period on performance and carcass characteristics in grain fed steers.
      This study was conducted as a completely randomized block design with 126 cross
      bred steer calves (initial BW 471.5 +/- 7.5 kg) randomly assigned to pens with 9
      steers/pen (n = 7 pens/treatment). Each pen was randomly assigned to one of two
      treatment groups; rumen bypass fat treatment (CCS, calcium soap of palm fatty
      acids) and control diet (CT, tallow). The diets were formulated to be
      isonitrogenous and isocaloric. Animals were fed twice daily at 110 % of the
      previous daily ad libitum intake. Blood from each sample was taken from the
      jugular vein. Muscle and adipose samples were collected from the longissimus
      dorsi regions. Feedlot performance and carcass characteristics were assessed. To
      examine adipogenic gene expression, quantitative real-time PCR was completed.
      Steers fed the CT had a greater level of performance for most of the parameters
      measured. The CT group had greater DMI (P < 0.05) and tended to have greater ADG
      (P < 0.10). Marbling score (P < 0.05) and quality grade (P < 0.05) were greater
      for steers fed the CT diet than those fed CCS. The longissimus muscle area tended
      to be greater (P < 0.10) in steers fed CT (87.60 cm(2)) than those fed CCS (84.88
      cm(2)). The leptin mRNA expression was down-regulated (P < 0.05) in adipose
      tissue of steers fed a CCS when compared to those fed CT. These data suggest that
      calcium soap of palm fatty acids can be added to finishing diets without
      significant reduction in final body weight, although there may be modest
      reductions in marbling and quality scores. 

PMID- 26290746
TI  - Effects of extrusion of rice bran on performance and phosphorous bioavailability
      in broiler chickens.
AB  - BACKGROUND: Rice bran is a by-product of the rice-milling process, which remains
      largely underutilized; however, efficient processing treatments may improve its
      feeding value for chickens. This is of great economic and environmental
      importance, as this can lower the production costs, and offer an opportunity for
      valorization of a low-quality agricultural by-product, to a high-value feed
      source. METHODS: This experiment was conducted to study the effect of extruded
      rice bran on performance and phosphorous (P) bioavailability in broiler chickens.
      In a completely randomized design, 200 seven-day-old broilers (Cobb 500) were
      allotted to five treatments with five replicates per treatment and 8 chicks per
      replicate, and fed with their respective diet during the starter (8 to 21 days)
      and grower (22 to 42 days) periods. Diets were a basal corn-soybean based diet
      (T1), or diets containing 20 % rice bran (T2), 30 % rice bran (T3), 20 % extruded
      rice bran (T4), or 30 % extruded rice bran (T5). RESULTS: Birds feeding on T4 and
      T5 diets had a higher body weight gain and lower feed-to-gain ratio compared to
      those feeding on T2 and T3 diets (p < 0.05). Birds receiving diets containing
      extruded rice bran had higher total P availability and tibia ash content, as
      compared with those receiving diets containing un-extruded rice bran (p < 0.05).
      Relative weight of the pancreas was higher in birds receiving T2 and T3 diets.
      CONCLUSIONS: The results confirmed the beneficial effect of extrusion treatment
      of rice bran on performance and P availability in broilers. Up to 30 % extruded
      rice bran may be included in the broiler diet without apparent adverse effects on
      the performance.

PMID- 26290747
TI  - In vitro maturation of ovine oocyte in a modified granulosa cells co-culture
      system and alpha-tocopherol supplementation: effects on nuclear maturation and
      cleavage.
AB  - This study was designed to investigate the effects of alpha-tocopherol and
      granulosa cells monolayer on nuclear maturation and cleavage rates of ovine
      cumulus-oocyte complexes (COCs). The COCs (n = 2814) were matured in maturation
      medium supplemented with various concentration of alpha-tocopherol (0, 5, 10, 15
      MUg/ml), oocytes were incubated at 39  degrees C with 5 % CO2 for 24 h in three
      culture systems: (a) maturation medium (MM; n = 884), (b) co-cultured with
      granulosa cells (CG; n = 982) and (c) co-cultured with granulosa cells and cells
      were further cultured in MM for 12 h (CG + 12hMM; n = 948). Our results showed
      that alpha-tocopherol had no effect on GVBD and MII as compared to control group,
      but when alpha-tocopherol added to maturation medium the rate of cleavage
      decreased. This indicates interaction of above mentioned factors in any of the
      treatments showed no significant differences on the rate of maturation and
      cleavage stages (MII, GVBD and cleavage) (p > 0.05). The oocytes co-cultured with
      granulosa cells for 24 h had beneficial effects on cleavage rate. The maximum MII
      and cleavage rates were achieved when oocytes had extra 12 h culture in the
      maturation medium without granulosa cells. Results also showed our modified co
      culture system (CG + 12hMM), improved rates of MII and the cleavage in comparison
      with other studied maturation systems. 

PMID- 26290748
TI  - A Comparison of Dexmedetomidine, Moxonidine and Alpha-Methyldopa Effects on
      Acute, Lethal Cocaine Toxicity.
AB  - BACKGROUND: The treatment of cocaine toxicity is an important subject for
      emergency physicians. We investigated the effects of dexmedetomidine, moxonidine
      and alpha-methyldopa on acute cocaine toxicity in mice. OBJECTIVES: The aim of
      this study was to evaluate the effects of dexmedetomidine, moxonidine and alpha
      methyldopa in a mouse model of acute cocaine toxicity. MATERIALS AND METHODS: We
      performed an experiment consisting of four groups (n = 25 each). The first group
      received normal saline solution, the second group received 40 ug/kg of
      dexmedetomidine, the third group received 0.1 mg/kg of moxonidine and the fourth
      group received 200 mg/kg of alpha-methyldopa, all of which were intraperitoneally
      administered 10 minutes before cocaine hydrochloride (105 mg/kg). All animals
      were observed for seizures (popcorn jumping, tonic-clonic activity, or a loss of
      the righting reflex) and lethality over the 30 minutes following cocaine
      treatment. RESULTS: The ratio of animals with convulsions was lower in all
      treated groups when compared to the control (P < 0.001). Furthermore, 68% (n =
      17) of animals in the dexmedetomidine group, 84% (n = 21) of the alpha-methyldopa
      group, 92% (n = 23) of the moxonidine group and 100% (n = 25) of the control
      group showed evidence of seizure activity (P = 0.009). Cocaine-induced lethality
      was observed in 12% (n = 3) of the dexmedetomidine group, 48% (n = 12) of the
      alpha-methyldopa group, 52% (n = 13) of the moxonidine group, and 72% (n = 18) of
      the control group (P < 0.001). All treatments prolonged the time to seizure,
      which was longest in the dexmedetomidine group (P > 0.05). In addition, the time
      to lethality was also longer in the same group (P < 0.001). CONCLUSIONS: The
      present study provides the first experimental evidence in support of
      dexmedetomidine treatment for cocaine-induced seizures. Premedication with
      dexmedetomidine reduces seizure activity in a mouse model of acute cocaine
      toxicity. In addition, while dexmedetomidine may be effective, moxonidine and
      alpha-methyldopa did not effectively prevent cocaine-induced lethality.

PMID- 26290749
TI  - Family-Centered Education and Its Clinical Outcomes in Patients Undergoing
      Hemodialysis Short Running.
AB  - BACKGROUND: Poor adherence to treatment in patients undergoing hemodialysis leads
      to many complications, including death of the patient. OBJECTIVES: This study was
      aimed to investigate the effect of family-based training on common side-effects
      during dialysis. PATIENTS AND METHODS: The present randomized controlled trial
      study was conducted on 60 patients undergoing hemodialysis at hospitals of Tehran
      University of Medical Sciences, Iran, from May 2012 to October 2012. Samples were
      randomly divided into two groups of patient-education (n = 30) and education of
      patient associated with an active member of the family (n = 30). Blood pressure,
      chest pain, nausea, vomiting, headaches and muscle cramps were followed with a
      check list and a questionnaire. The frequencies of the abovementioned
      complications at the mentioned intervals were recorded in three stages (before
      the intervention as well as two and four weeks after the intervention). Data
      analysis was performed using SPSS software, version 16, with chi-square test,
      Fisher's exact test and independent t-test. RESULTS: The mean ages of the
      patients in patient-centered and the family-oriented groups were 47.41 +/- 10.31
      and 48.16 +/- 9.21, respectively. The result showed that some of the variables
      such as chest pain (P = 0.50, P = 0.01), nausea (P = 0.50, P = 0.01), headache (P
      = 0.81, P = 0.016), and blood pressure (P = 0.91, P = 0.016) were statistically
      significant before and four weeks after the intervention. CONCLUSIONS: According
      to the result of this study, the presence of families in a treatment plan could
      be essential to follow the treatment plan and subsequently reduced the
      complications of hemodialysis.

PMID- 26290750
TI  - Decreased Activity in Neuropathic Pain Form and Gene Expression of Cyclin
      Dependent Kinase5 and Glycogen Synthase Kinase-3 Beta in Soleus Muscle of Wistar
      Male Rats.
AB  - BACKGROUND: The relationship between decreased activity/neuropathic pain and gene
      expression alterations in soleus muscle has remained elusive. OBJECTIVES: In this
      experimental study, we investigated the effects of decreased activity in
      neuropathic pain form on Cyclin-Dependent Kinase 5 (CDK5) and Glycogen Synthase
      Kinase-3 beta (GSK-3beta) gene expression in soleus muscle of rats. MATERIALS AND
      METHODS: Twelve male Wistar rats were randomly divided into three groups: (1)
      tight ligation of the L5 spinal nerve (SNL: n = 4); (2) sham surgery (Sham: n =
      4), and (3) control (C: n = 4). The threshold to produce a withdrawal response to
      a mechanical and thermal stimulus was measured using von Frey filaments and
      radiation heat apparatus, respectively. Following 4 weeks after surgery, the left
      soleus muscle was removed and mRNA levels were determined by real-time Polymerase
      Chain Reaction (PCR). RESULTS: Compared to control animals, L5 ligated animals
      developed mechanical and heat hypersensitivity during total period of study.
      Soleus muscle weight as well as CDK5 mRNA levels (less than ~ 0.4 fold) was
      decreased and GSK-3beta mRNA levels (up to ~ 7 folds) increased in L5 ligated
      animals. CONCLUSIONS: These results showed enhanced muscle atrophy processes
      following peripheral nerve damage and might provide a useful approach to study
      underlying muscle mechanisms associated with clinical neuropathic pain syndromes.

PMID- 26290751
TI  - Perception of Patients With HIV/AIDS From Stigma and Discrimination.
AB  - BACKGROUND: Stigma and discrimination among patients with HIV/AIDS cause various
      problems for the patients and their health systems. OBJECTIVES: The purpose of
      this study was to explain the perceived experiences of the patients from stigma
      and discrimination and their roles on health-seeking services among patients.
      PATIENTS AND METHODS: This was a qualitative research using content analysis
      approach and semi-structured interviews, conducted on patients living with
      HIV/ADS, during 2013 - 2014 in Iran. Sampling started purposefully and continued
      in a snowball. RESULTS: The experiences of patients with HIV/AIDS from stigma and
      discrimination led to exploring three main themes and nine subthemes. The main
      themes were multidimensional stigma, rejection, and insult and discrimination in
      receiving health services. CONCLUSIONS: Stigma and discrimination play an
      important role in patients' lives and hinder them from accessing the treatment.
      The patients' responses to this event by secrecy strategy can be an important
      factor in the disease prevalence.

PMID- 26290752
TI  - Iranian Health Literacy Questionnaire (IHLQ): An Instrument for Measuring Health
      Literacy in Iran.
AB  - BACKGROUND: Promoting Health Literacy (HL) is considered as an important goal in
      strategic plans of many countries. In spite of the necessity for access to valid,
      reliable and native HL instruments, the number of such instruments in the Persian
      language is scarce. Moreover, there is no good estimation of HL status in Iran.
      OBJECTIVES: The aim of this study was to provide a valid, reliable and native
      instrument to measure and monitor community HL in Iran and also, to provide an
      estimation of HL status in two Iranian provinces. PATIENTS AND METHODS: By
      applying the multistage cluster sampling, 1080 respondents (540 from each gender)
      were recruited from Kerman and Mazandaran provinces of Iran, from February to
      June 2014 to participate in this cross-sectional study. The development of the
      Iranian Health Literacy Questionnaire (IHLQ) was initiated with a comprehensive
      review of the literature. Then, face, content and construct validity as well as
      reliability were determined. RESULTS: Internal consistency and test-retest
      reliability (ICC) of the factors was in the range of 0.71 to 0.96 and 0.73 to
      0.86, respectively. In order to construct validity, Exploratory Factor Analysis
      (EFA) Kaiser-Meyer-Olkin (KMO) = 0.95 and Bartlett's test result of 3.017 with P
      < 0.001) with varimax rotation was used. Optimal reduced solution, including 36
      items and seven factors, was found in EFA. Five of the factors identified were
      reading/comprehension skills, individual empowerment, communication/decision
      making skills, social empowerment and health knowledge. CONCLUSIONS: It was
      concluded that IHLQ might be a practical and useful tool for investigating HL for
      Persian language speakers around the world. Since HL is dynamic and its
      instruments should be regularly revised, further studies are recommended to
      assess HL with application of IHLQ to detect its potential imperfections.

PMID- 26290753
TI  - Behavioral Change Challenges in the Context of Center-Based Cardiac
      Rehabilitation: A Qualitative Study.
AB  - BACKGROUND: Cardiovascular disease is chronic and often a sign of long-standing
      unhealthy lifestyle habits. Patients need support to reach lifestyle changes,
      well-being, join in social and vocational activity. Thus, patient responsibility
      should to be encouraged to provide quality as well as longevity. Cardiac
      rehabilitation programs aid patients in the attainment of these objectives.
      However, research shows that behavioral change following the diagnosis of a
      chronic disease is a challenge. OBJECTIVES: We sought to determine behavioral
      change challenges in patients with cardiovascular disease to improve intervention
      programs. PATIENTS AND METHODS: Using a descriptive qualitative approach, we
      collected the data using 30 in-depth semi-structure interviews. Thematic analysis
      was conducted to identify themes from the data. RESULTS: Three sources of
      behavioral change challenges emerged regarding the nature of cardiac disease and
      the role of the individual and the family in the recovery process. These
      challenges acted at two levels: intra- and interpersonal. The intrapersonal
      factors comprised value, knowledge and judgment about cardiovascular disease, and
      self-efficacy to fulfill the rehabilitation task. Family overprotection
      constituted the principal component of the interpersonal level. CONCLUSIONS:
      Behaviors are actually adopted and sustained by patients are so far from that
      recommended by health professionals. This gap could be reduced by identifying
      behavioral change challenges, rooted in the beliefs of the individual and the
      family. Therefore, culturally-based interventions to enhance disease self
      management should be considered.

PMID- 26290754
TI  - Demographic and Socioeconomic Factors of Patients With Coronary Artery Diseases
      Undertreatment of Coronary Artery Bypass Grafting, Percutaneous Coronary
      Intervention and Drug Therapy in Mashhad, Iran.
AB  - BACKGROUND: Considering the importance of preventing cardiovascular diseases,
      determining the contributing risk factors for ischemic heart disease which leads
      to atherosclerotic plaque, could be effective in selecting the required
      interventions. OBJECTIVES: This study aimed to evaluate socioeconomic factors in
      patients with Coronary Artery Diseases (CAD) in three treatment groups: Coronary
      Artery Bypass Grafting (CABG), Percutaneous Coronary Intervention (PCI) and drug
      therapy. By identifying and comparing the underlying factors in treatment groups,
      we can gather useful information for future planning and policy making in order
      to reduce and eliminate the contributing factors. PATIENTS AND METHODS: This
      cross-sectional study was conducted on 760 patients with CAD referred to
      cardiovascular health centers in Mashhad, Iran, including Javad-Al-Aeme Heart
      Hospital, Qaem, Imam Reza and Dr. Shariati educational Hospital. Samples were
      collected through purposive sampling from January to March 2014. Based on the
      experts' opinion, the subjects were categorized into three treatment groups:
      CABG, PCI, and drug therapy. RESULTS: The mean age of total patients was 58.3 +/-
      11.5 years (P = 0.09). The proportion of rural patients in the PCI (26.7%) and
      drug therapy (27.5%) groups was twice as high as the CABG group (11.7%) (P <
      0.001). The proportion of patients with higher educational level (higher than
      high school diploma) in the CABG group (35.9%) was higher than PCI and drug
      therapy groups (26.7%, 24.3%) (P = 0.006). Smoking, drinking and drug abuse were
      more common in the drug therapy group (P = 0.03, P = 0.02, and P < 0.001,
      respectively). One-vessel and three-vessel coronary artery diseases were more
      common in the drug and CABG groups, respectively (P < 0.001). CONCLUSIONS: In
      total, application of therapeutic approaches in patients with CAD depends on many
      factors. In our study not only risk factors such as gender, lifestyle, smoking,
      alcohol abuse, diabetes and hypertension were associated with the incidence of
      CAD, but also they were highly correlated with the severity of the disease.

PMID- 26290755
TI  - Detection of Antibodies against Human and Plant Aquaporins in Patients with
      Multiple Sclerosis.
AB  - Multiple sclerosis (MS) is an autoimmune disease that affects the body's central
      nervous system. Around 90% of MS sufferers are diagnosed with relapsing-remitting
      MS (RRMS). We used ELISA to measure IgG, IgA, and IgM antibodies against linear
      epitopes of human and plant aquaporins (AQP4) as well as neural antigens in RRMS
      patients and controls to determine whether patients suffering from RRMS have
      simultaneous elevations in antibodies against these peptides and antigens. In
      comparison to controls, significant elevations in isotype-specific antibodies
      against human and plant AQP4 and neural antigens such as MBP, MOG, and S100B were
      detected in RRMS patients, indicating a high correlation in antibody reaction
      between plant aquaporins and brain antigens. This correlation between the
      reactivities of RRMS patients with various tested antigens was the most
      significant for the IgM isotype. We conclude that a subclass of patients with
      RRMS reacts to both plant and human AQP4 peptides. This immune reaction against
      different plant aquaporins may help in the development of dietary modifications
      for patients with MS and other neuroimmune disorders. 

PMID- 26290756
TI  - Use of Digital Panoramic Radiographs in the Study of Styloid Process Elongation.
AB  - This work aimed to evaluate the occurrence of suggestive images of styloid
      process elongation in panoramic radiographs, noting their frequency according to
      sex, age, and location, as well as measure and classify the types and patterns of
      calcification of elongated styloid processes. 2,500 panoramic radiographs were
      evaluated in a Radiology Clinic in Recife, PE, Brazil, performed between 2008 and
      2010, with the age ranging from 25 to 80 years old. 560 of the radiographs
      analyzed fulfilled the inclusion criteria. Of this total, 216 (38.57%) presented
      suggestive images of the styloid process elongation, 45 (20.8%) belonging to male
      and 171 (79.2%) to female, and 84.7% were bilateral. After all measurements, mean
      values of 35.5 mm (left side) and 37.6 mm (right side) were obtained and these
      differences were statistically significant (p < 0.001). The most common type of
      stretching found was elongated (type I) with 73.1%, and the pattern of
      calcification was partially calcified (62.5%). It was found that the elongation
      of the styloid process is an anatomical variation, which must be taken into
      account by dentists, and because panoramic radiography is a technique of easy
      approach and low cost and routine, it can be used to aid in the diagnosis of
      elongated styloid process. 

PMID- 26290757
TI  - Neuropsychological Symptoms among Workers Exposed to Toluene and Xylene in Two
      Paint Manufacturing Factories in Eastern Thailand.
AB  - The study analyzed the exposure factors that may lead to neuropsychological
      symptoms among 92 workers who were exposed to xylene and toluene and 100 workers
      who were not exposed to the solvents. The airborne concentration of xylene and
      toluene was evaluated with personal passive badges. The levels of methyl hippuric
      acid and hippuric acid in urine were assessed, and interviews were performed to
      observe the neuropsychological symptoms that may result from exposure to the
      solvents. The result showed that the average concentration for the exposed group
      of xylene in the paint company working environment was 2.7 (SD = 2.4) ppm and the
      average concentration of toluene was 9.5 (SD = 10.4) ppm. The average level of
      methyl hippuric acid in urine was 78 (SD = 74.7) mg/g creatinine. Factors that
      affected the neuropsychological symptoms included the following. (1) The impact
      of age: the risk (adjusted odds ratio) for getting psychosomatic symptoms in
      persons over 40 and exposed to xylene was 9.5 and the aOR of those exposed to
      toluene was 8.3. (2) The impact of not providing personal protective equipment
      was found to be sleep disturbance; it was found that the aOR of those exposed to
      xylene was 3.9, and the aOR of those exposed to toluene was 4.4. In summary,
      periodic examination of workers by occupational physician is needed for detection
      of early neuropsychological effects, especially psychosomatic symptoms, and sleep
      disturbances. 

PMID- 26290758
TI  - Combined Negative- and Positive-Pressure Ventilation for the Treatment of ARDS.
AB  - Objective. Tracheal intubation and positive-pressure ventilation as the current
      standard of care for the adult respiratory distress syndrome (ARDS) seem to have
      reached their limit in terms of a further relevant reduction of the still very
      high mortality. Case Presentation. A 75-year-old male patient developed ARDS
      after abscess drainage with deteriorating oxygenation, despite positive end
      expiratory pressure (PEEP) values above 15 cm H2O. We applied external negative
      pressure ventilation with a chamber respirator using -33 cm H2O at inspiration
      and -15 cm H2O at expiration, combined with conventional pressure support using a
      PEEP of about 8 cm H2O and a pressure support of 4-12 cm H2O. Alveolar
      infiltrates disappeared rapidly and PaO2/FiO2 values surpassed 300 mmHg after the
      first application and 500 mmHg after the second. Negative-pressure ventilation
      was used for 6-18 hours/day over five days. Now, 13 years later, the patient is
      still alive and has a good quality of life. Conclusion. Using this or similar
      concepts, not only in intubated patients but also as a noninvasive approach in
      patients with ARDS, offers new options that may genuinely differ from the present
      therapeutic approaches and may, therefore, have the potential to decrease the
      present high mortality from ARDS. 

PMID- 26290759
TI  - Dipeptidyl Peptidase-4 Inhibition May Stimulate Progression of Carcinoid Tumor.
AB  - Dipeptidyl peptidase-4 (DPP-4) inhibitors, such as saxagliptin, have gained a
      rapid growth in use in the treatment of type 2 diabetes mellitus in the past
      decade. Although they are considered to have a good safety profile, controversy
      exists regarding their potential to stimulate neoplasm growth. We report here a
      patient with metastatic carcinoid tumor. His disease was stable for several years
      with plasma serotonin level (which was used to monitor disease progression) in
      700-800 ng/mL range. After initiation of treatment with saxagliptin, however, his
      serotonin level almost doubled (1358 ng/mL), concerning progression of the
      disease. After discontinuation of saxagliptin, serotonin level returned to
      baseline quickly, while other laboratory markers, such as complete blood count
      (CBC), comprehensive metabolic profile (CMP) with liver function tests (LFTs),
      and lactate dehydrogenase (LD), remained unchanged before, during, and after the
      treatment with saxagliptin. This temporal correlation suggests a possible
      interaction between the activity of carcinoid tumors and the use of DPP-4
      inhibitors. Although we were not able to find any literature providing a direct
      evidence that saxagliptin alters progression of the carcinoid tumors, we
      recommend alternative management for the treatment of diabetes in patients with
      carcinoid or other neuroendocrine tumors. 

PMID- 26290760
TI  - Disseminated Herpes Simplex Virus with Fulminant Hepatitis.
AB  - Disseminated herpes simplex virus (HSV) is a rare cause of acute fulminant liver
      failure. We hereby present a case series of three patients with acute
      disseminated HSV with necrotizing hepatitis successfully treated with a week
      course of acyclovir. Early empiric administration of acyclovir therapy while
      awaiting confirmatory tests is critical in this potentially lethal disease. 

PMID- 26290761
TI  - Levamisole/Cocaine Induced Systemic Vasculitis and Immune Complex
      Glomerulonephritis.
AB  - Levamisole is an antihelminthic and immunomodulator medication that was banned by
      the USFDA in 1998. It has been increasingly used to adulterate cocaine due to its
      psychotropic effects and morphological properties. Adverse reactions including
      cutaneous vasculitis, thrombocytopenia, and agranulocytosis have been well
      described. Despite systemic vasculitis in this setting, renal involvement is
      uncommon. We report here a case of ANCA positive systemic vasculitis with biopsy
      proven immune complex mediated glomerulonephritis likely secondary to
      levamisole/cocaine. A 40-year-old Caucasian male with no past medical history
      presented with 3-week history of fatigue, skin rash, joint pains, painful oral
      lesions, oliguria, hematuria, worsening dyspnea on exertion, and progressive
      lower extremity edema. He had a history of regular tobacco and cocaine use. Lab
      testing revealed severe anemia, marked azotemia, deranged electrolytes, and 4.7
      gm proteinuria. Rheumatologic testing revealed hypocomplementemia, borderline
      ANA, myeloperoxidase antibody, and positive atypical p-ANCA. Infectious and other
      autoimmune workup was negative. Kidney biopsy was consistent with immune mediated
      glomerulonephritis and showed mesangial proliferation and immune complex
      deposition consisting of IgG, IgM, and complement. High dose corticosteroids and
      discontinuing cocaine use resulted in marked improvement in rash, mucocutaneous
      lesions, and arthritis. There was no renal recovery and he remained hemodialysis
      dependent. 

PMID- 26290762
TI  - Crossed Renal Ectopia without Fusion: An Uncommon Cause of Abdominal Mass.
AB  - Crossed renal ectopia is a rare congenital anomaly usually associated with fused
      kidneys (90%). Most cases are asymptomatic and remain undiagnosed. We report an
      unusual case of nonfused crossed renal ectopia. The 11-year-old adolescent female
      patient was admitted with abdominal pain, anorexia, weight loss, and
      periumbilical mass. Although the initial clinical suspicion was a tumoral lesion,
      abdominal ultrasound and magnetic resonance examination revealed crossed renal
      ectopia without fusion. The renal ectopy was incidentally diagnosed, as described
      in 20 to 30% of cases. In this case, the associated nonspecific symptoms were a
      coincidence. 

PMID- 26290763
TI  - Small Bowel Adenocarcinoma as the Cause of Gastrointestinal Bleeding in Celiac
      Disease: A Rare Malignancy in a Common Disease.
AB  - Introduction. Celiac disease is associated with an increased risk of small bowel
      malignancies, particularly lymphoma. Its association with small bowel carcinoma
      is less known. Case Description. We report a case of an 89-year-old woman with
      celiac disease who experienced recurrent episodes of gastrointestinal bleeding
      and was ultimately found to have adenocarcinoma of the small intestine.
      Discussion and Evaluation. Diagnosis of small bowel adenocarcinoma is often
      delayed because of the need for specialized modalities, which are often deferred
      in the inpatient setting. Although resection is the modality of choice for small
      bowel tumors, a majority is either locally advanced or metastatic at diagnosis,
      and even localized cancers have worse prognosis than stage-matched colorectal
      tumors. The role of adjuvant chemotherapy is uncertain, but it is often offered
      extrapolating data from other gastrointestinal cancers. Small bowel carcinomas
      occurring in the context of celiac disease appear to be associated with higher
      rates of microsatellite instability than sporadic tumors, although other specific
      genomic abnormalities and mechanisms of carcinogenesis in celiac disease remain
      unknown. Conclusion. Recurrent episodes of gastrointestinal bleeding in a patient
      with celiac disease should prompt an early evaluation of the small bowel to
      assure timely diagnosis of carcinoma at an early curable stage. 

PMID- 26290764
TI  - Tracheal Diverticulum: A Unique Case with Intraoperative Morphologic Assessment.
AB  - There are rare case reports of tracheal diverticula or paratracheal air cysts.
      These cases, however, were reported mostly as incidental sonographic or
      radiologic findings without histologic confirmation. Furthermore, the handful of
      studies that describe this entity histopathologically report only cases in
      patients with prior respiratory symptoms. Here, we report a rare case of an
      asymptomatic 60-year-old female with no significant past medical history who
      presented with primary hyperparathyroidism. She was found to have an incidental
      right paraesophageal air-filled diverticulum with multiple thin septations on her
      imaging studies. She was taken to surgery and the histologic examination of the
      specimen revealed multiloculated cystic cavity lined by respiratory-type columnar
      epithelium with lymphocytic infiltrate and minor salivary glands within the
      surrounding stroma, rendering the diagnosis of tracheal diverticula. 

PMID- 26290765
TI  - Management of a Gastrobronchial Fistula Connected to the Skin in a Giant
      Extragastric Stromal Tumor.
AB  - Introduction. Gastrointestinal stromal tumors first treatment should be surgical
      resection, but when metastases are diagnosed or the tumor is unresectable,
      imatinib must be the first option. This treatment could induce some serious
      complications difficult to resolve. Case Report. We present a 47-year-old black
      man with a giant unresectable gastric stromal tumor under imatinib therapy who
      presented serious complications such as massive gastrointestinal bleeding and a
      gastrobronchial fistula connected with the skin, successfully treated by surgery
      and gastroscopy. Discussion. Complications due to imatinib therapy can result in
      life threatening. They represent a challenge for surgeons and digestologists;
      creative strategies are needed in order to resolve them. 

PMID- 26290766
TI  - The Impact of Radiation on an Unusual Case of Omental Epithelioid Angiosarcoma.
AB  - Epithelioid angiosarcoma is a rare high-grade tumor with irregular vascular
      morphology. We report an unusual case of intra-abdominal epithelioid angiosarcoma
      affecting the omentum and peritoneal surfaces resulting in significant
      hemorrhagic and inflammatory changes. As in other cases of this tumor this
      patient had previously undergone radiation treatment for a history of cervical
      cancer. 

PMID- 26290767
TI  - Radical Cystectomy with Ileal Conduit Urinary Diversion in a Patient with a Left
      Ventricular Assist Device.
AB  - Left ventricular assist device (LVAD) is an option for the surgical management of
      severe heart failure, and radical cystectomy remains the standard of care for
      muscle-invasive bladder cancer. Given a complicated population in terms of
      comorbidities and management for patients with an LVAD, there is little
      experience with major urologic procedures, which require balancing the benefits
      of surgery with considerable perioperative risks. We report our experience
      performing the first radical cystectomy with ileal conduit in a patient with an
      LVAD and muscle-invasive bladder cancer. 

PMID- 26290768
TI  - Papillary Renal Cell Carcinoma Seeding along a Percutaneous Biopsy Tract.
AB  - We report a case of tumour seeding caused by percutaneous biopsy of a papillary
      renal cell carcinoma detected on pathological assessment of the partial
      nephrectomy specimen in a 50-year-old male. Whilst percutaneous biopsy of renal
      masses is considered to be safe and can be a valuable tool in the assessment of
      certain renal lesions, it is not without risks. This rare complication should be
      taken into consideration before contemplating its use in a patient. 

PMID- 26290769
TI  - Tumor Growth Mitigating Effects of Valproic Acid in Systemic Malignancies.

PMID- 26290770
TI  - Using Chemical Release Surveillance Data to Evaluate the Public Health Impacts of
      Chlorine and Its Alternatives.
AB  - BACKGROUND: More than 80 million Americans may be at risk of a chemical exposure
      because they live near one of the 101 most hazardous chemical facilities or near
      routes used to transport hazardous chemicals. One approach to hazard reduction is
      to use less toxic alternatives. Chlorine, one of the chemicals posing the
      greatest public health danger, has several alternatives depending on the
      application. METHODS: We analyzed data collected during 1993-2008 by 17 state
      health departments participating in the Agency for Toxic Substances and Disease
      Registry's (ATSDR) active chemical incident surveillance program. We conducted
      descriptive analyses to evaluate whether five chlorine alternatives (calcium
      hypochlorite, hydrogen peroxide, sodium chlorate, sodium hydrosulfite, and sodium
      hypochlorite) resulted in less severe incidents. We used chi square and z-score
      analyses to test significance, where appropriate. RESULTS: During 1993-2008, 2040
      incidents involved chlorine, and 1246 incidents involved chlorine alternatives.
      Nearly 30% of chlorine releases resulted in injured persons, as compared to 13%
      of chlorine alternatives that resulted in injury. Although similar proportions of
      persons injured in chlorine or chlorine alternative releases were treated on
      scene (18% and 14%, respectively) and at a hospital (58% and 60%, respectively),
      there was a greater proportion of hospital admissions following chlorine releases
      than there was following releases of chlorine alternatives (10 % vs. 4%) (p <
      0.01). There were significantly fewer victims per release for hydrogen peroxide
      (0.2) than there were for chlorine (1.3) in paper manufacturing (p < 0.01).
      CONCLUSION: Exposures to these five potential chlorine alternatives resulted in a
      lower proportion of exposed persons requiring hospital admission. To reduce acute
      public health injuries associated with chemical exposures, users should consider
      a chlorine alternative when such a substitution is reasonable.

PMID- 26290771
TI  - Endovascular management of fusiform aneurysm of anterior temporal artery:
      Technical report.
AB  - BACKGROUND: The treatment of a rare, nontraumatic, fusiform aneurysm of the
      anterior temporal artery (ATA) via endovascular techniques is presented, and
      procedural nuances are highlighted. METHODS: We performed a retrospective chart
      review and collected demographic and clinical data on the patient presented here;
      procedural details were extracted from operative notes. RESULTS: Following
      successful balloon test occlusion (BTO) of the ATA, complete coil embolization of
      the ATA, and its associated fusiform aneurysm was performed. Postprocedurally,
      the patient did not suffer any adverse neurological sequelae. CONCLUSION:
      Selective BTO of intracranial branch vessels is safe, technically feasible, and
      could serve as a useful technical tool in the treatment of complex, fusiform
      intracranial aneurysms.

PMID- 26290772
TI  - Midline as a landmark for the position of the superior sagittal sinus on the
      cranial vault: An anatomical and imaging study.
AB  - BACKGROUND: Craniotomies involving the midline are regular practice in
      neurosurgery, during which injury to the superior sagittal sinus (SSS), an
      uncommon yet devastating event, may occur. The midline tends to be the most
      common landmark used to identify the position of the SSS. In this study we
      examined the reliability of the midline as a landmark for the SSS. METHODS: We
      performed bilateral craniectomies on eight cadaveric heads, preserving the
      coronal, sagittal, and lambdoid sutures. The width of the SSS and its
      displacement from midline were measured on the cadaveric specimens and on 105
      normal magnetic resonance images (MRIs) of the head at the following locations:
      halfway between nasion and bregma (NB), bregma (B), halfway between bregma and
      lambda (BL), lambda (L), and inion (I). RESULTS: In all cadaveric specimens, the
      SSS was partially or totally displaced toward one side of midline, usually to the
      right. It tended to be closer to midline in the frontal region and more displaced
      posteriorly. The SSS usually drained into the right-side transverse sinus. The
      mean width of the SSS was 4.3, 5.9, 6.9, 7.9, and 7.8 mm, and the average
      displacement from midline was 4.3, 6.3, 5.5, 6.9, and 6.0 mm for NB, B, BL, L,
      and I, respectively. These measurements were then compared with those obtained
      from the MRIs. CONCLUSION: The SSS was consistently displaced on either side of
      midline. Thus, the midline is not reliable for identifying the SSS, and caution
      should be used within 6-10 mm on either side of midline.

PMID- 26290773
TI  - Temporary deep brain stimulation in Gilles de la Tourette syndrome: A feasible
      approach?
AB  - BACKGROUND: Gilles de la Tourette Syndrome (GTS) is a complex neuropsychiatric
      disorder, characterized by chronic motor and vocal tics, associated in 50-90% of
      cases with psychiatric comorbidities. Patients with moderate and severe clinical
      picture are treated with psychotherapy and pharmacological therapy. Deep brain
      stimulation (DBS) is reserved for pharmacological refractory GTS patients. As GTS
      tends to improve with time and potentially resolves in the second decade of life,
      the major concern of DBS in GTS is the age at which the patient undergoes
      surgical procedure. Some authors suggest performing DBS after 18 years, others
      after 25 years of age. CASE DESCRIPTION: We present a 25-year-old patient with
      GTS, who was aged 17 years and was treated with thalamic DBS. DBS resulted in
      progressive and sustained improvement of tics and co-morbidities. After 6 years
      of DBS treatment, it was noted that the clinical improvement was maintained also
      in OFF stimulation setting, so it was decided to keep it off. After 2 years in
      off-setting and stable clinical picture the entire DBS device was removed. Six
      months after DBS device removal the patient remained symptom-free. CONCLUSIONS:
      DBS is a therapeutic option reserved for severe and refractory GTS cases. In our
      opinion DBS might be considered as a temporary application in GTS.

PMID- 26290775
TI  - ARVO Embraces Open Access.

PMID- 26290774
TI  - Neurological deaths of American adults (55-74) and the over 75's by sex compared
      with 20 Western countries 1989-2010: Cause for concern.
AB  - BACKGROUND: Have USA total neurological deaths (TNDs) of adults (55-74) and the
      over 75's risen more than in twenty Western Countries? METHODS: World Health
      Organization TND data are compared with control mortalities cancer mortality
      rates (CMRs) and circulatory disease deaths (CDDs) between 1989-1991 and 2008
      2010 and odds ratios (ORs) and confidence intervals calculated. RESULTS:
      Neurological Deaths - Twenty country (TC) average 55-74 male rates per million
      (pm) rose 2% to 503 pm, USA increased by 82% to 627 pm. TC average females rose
      1% to 390 pm, USA rising 48% to 560 pm. TC average over 75's male and female
      increased 117% and 143%; USA rising 368% and 663%, significantly more than 16
      countries. Cancer mortality - Average 55-74 male and female fell 20% and 12%, USA
      down 36% and 18%. TC average over 75's male and female fell 13% and 15%, the USA
      29% and 2%. Circulatory deaths - TC average 55-74 rates fell 60% and 46% the USA
      down 54% and 53%. Over 75's average down 46% and 39%, USA falling 40% and 33%.
      ORs for rose substantially in every country. TC average 75's ORs for CMR: TND
      male and females were 1:2.83 and 1:3.04 but the USA 1:5.18 and 1:6.50. The ORs
      for CDD: TND male and females TC average was 1:3.42 and 1:3.62 but the USA 1:6.13
      and 1:9.89. CONCLUSIONS: Every country's neurological deaths rose relative to the
      controls, especially in the USA, which is a cause for concern and suggests
      possible environmental influences.

PMID- 26290776
TI  - Integration of Perforated Subretinal Prostheses With Retinal Tissue.
AB  - PURPOSE: To investigate the integration of subretinal implants containing full
      depth perforations of various widths with rat and pig retina across weeks of
      implantation. METHODS: In transgenic P23H rhodopsin line 1 (TgP23H-1) rats and
      wild-type (WT) pigs, we examined four subretinal implant designs: solid inactive
      polymer arrays (IPA), IPAs with 5- or 10-MUm wide perforations, and active
      bipolar photovoltaic arrays (bPVA) with 5-MUm perforations. We surgically placed
      the implants into the subretinal space using an external approach in rats or a
      vitreoretinal approach in pigs. Implant placement in the subretinal space was
      verified with optical coherence tomography and retinal perfusion was
      characterized with fluorescein angiography. Rats were sacrificed 8 or 16 weeks
      post-implantation (wpi) and pigs 2, 4, or 8 wpi, and retinas evaluated at the
      light microscopic level. RESULTS: Regardless of implant design, retinas of both
      species showed normal vasculature. In TgP23H-1 retinas implanted with 10-MUm
      perforated IPAs, inner nuclear layer (INL) cells migrated through the
      perforations by 8 wpi, resulting in significant INL thinning by 16 wpi.
      Additionally, these retinas showed greater pseudo-rosette formation and fibrosis
      compared with retinas with solid or 5-MUm perforated IPAs. TgP23H-1 retinas with
      bPVAs showed similar INL migration to retinas with 5-MUm perforated IPAs, with
      less fibrosis and rosette formation. WT pig retina with perforated IPAs
      maintained photoreceptors, showed no migration, and less pseudo-rosette
      formation, but more fibrosis compared with implanted TgP23H-1 rat retinas.
      CONCLUSIONS: In retinas with photoreceptor degeneration, solid implants, or those
      with 5-MUm perforations lead to the best biocompatibility.

PMID- 26290778
TI  - Evaluating Red Reflex and Surgeon Preference Between Nearly-Collimated and
      Focused Beam Microscope Illumination Systems.
AB  - PURPOSE: To evaluate the intensity and stability of the red reflex produced by
      ophthalmic surgical microscopes with nearly-collimated versus focused
      illumination systems and to assess surgeon preference in a simulated surgical
      setting. METHODS: This two-part evaluation consisted of postproduction surgical
      video analysis of red reflex intensity and a microscope use and preference survey
      completed by 13 experienced cataract surgeons. Survey responses were based on
      bench testing and experience in a simulated surgical setting. A microscope with
      nearly-collimated beam illumination and two focused beam microscopes were
      assessed. RESULTS: Red reflex intensity and stability were greater with the
      nearly-collimated microscope illumination system. In the bench testing survey,
      surgeons reported that the red reflex was maintained over significantly greater
      distances away from pupillary center, and depth of focus was numerically greater
      with nearly-collimated illumination relative to focused illumination. Most
      participating surgeons (>=64%) reported a preference for the microscope with
      nearly-collimated illumination with regard to red reflex stability, depth of
      focus, visualization, surgical working distance, and perceived patient comfort.
      CONCLUSIONS: The microscope with nearly-collimated illumination produced a more
      intense and significantly more stable red reflex and was preferred overall by
      more surgeons. TRANSLATIONAL RELEVANCE: This is the first report of an attempt to
      quantify red reflex intensity and stability and to evaluate surgically-relevant
      parameters between microscope systems. The data and methods presented here may
      provide a basis for future studies attempting to quantify differences between
      surgical microscopes that may affect surgeon preference and microscope use in
      ophthalmic surgery.

PMID- 26290777
TI  - High Tech Aids Low Vision: A Review of Image Processing for the Visually
      Impaired.
AB  - Recent advances in digital image processing provide promising methods for
      maximizing the residual vision of the visually impaired. This paper seeks to
      introduce this field to the readership and describe its current state as found in
      the literature. A systematic search revealed 37 studies that measure the value of
      image processing techniques for subjects with low vision. The techniques used are
      categorized according to their effect and the principal findings are summarized.
      The majority of participants preferred enhanced images over the original for a
      wide range of enhancement types. Adapting the contrast and spatial frequency
      content often improved performance at object recognition and reading speed, as
      did techniques that attenuate the image background and a technique that induced
      jitter. A lack of consistency in preference and performance measures was found,
      as well as a lack of independent studies. Nevertheless, the promising results
      should encourage further research in order to allow their widespread use in low
      vision aids.

PMID- 26290779
TI  - Recursion to food plants by free-ranging Bornean elephant.
AB  - Plant recovery rates after herbivory are thought to be a key factor driving
      recursion by herbivores to sites and plants to optimise resource-use but have not
      been investigated as an explanation for recursion in large herbivores. We
      investigated the relationship between plant recovery and recursion by elephants
      (Elephas maximus borneensis) in the Lower Kinabatangan Wildlife Sanctuary, Sabah.
      We identified 182 recently eaten food plants, from 30 species, along 14 * 50 m
      transects and measured their recovery growth each month over nine months or until
      they were re-browsed by elephants. The monthly growth in leaf and branch or shoot
      length for each plant was used to calculate the time required (months) for each
      species to recover to its pre-eaten length. Elephant returned to all but two
      transects with 10 eaten plants, a further 26 plants died leaving 146 plants that
      could be re-eaten. Recursion occurred to 58% of all plants and 12 of the 30
      species. Seventy-seven percent of the re-eaten plants were grasses. Recovery
      times to all plants varied from two to twenty months depending on the species.
      Recursion to all grasses coincided with plant recovery whereas recursion to most
      browsed plants occurred four to twelve months before they had recovered to their
      previous length. The small sample size of many browsed plants that received
      recursion and uneven plant species distribution across transects limits our
      ability to generalise for most browsed species but a prominent pattern in plant
      scale recursion did emerge. Plant recovery time was a good predictor of time to
      recursion but varied as a function of growth form (grass, ginger, palm, liana and
      woody) and differences between sites. Time to plant recursion coincided with
      plant recovery time for the elephant's preferred food, grasses, and perhaps also
      gingers, but not the other browsed species. Elephants are bulk feeders so it is
      likely that they time their returns to bulk feed on these grass species when
      quantities have recovered sufficiently to meet their intake requirements. The
      implications for habitat and elephant management are discussed. 

PMID- 26290780
TI  - Comprehensive analyses of genomes, transcriptomes and metabolites of neem tree.
AB  - Neem (Azadirachta indica A. Juss) is one of the most versatile tropical evergreen
      tree species known in India since the Vedic period (1500 BC-600 BC). Neem tree is
      a rich source of limonoids, having a wide spectrum of activity against insect
      pests and microbial pathogens. Complex tetranortriterpenoids such as
      azadirachtin, salanin and nimbin are the major active principles isolated from
      neem seed. Absolutely nothing is known about the biochemical pathways of these
      metabolites in neem tree. To identify genes and pathways in neem, we sequenced
      neem genomes and transcriptomes using next generation sequencing technologies.
      Assembly of Illumina and 454 sequencing reads resulted in 267 Mb, which accounts
      for 70% of estimated size of neem genome. We predicted 44,495 genes in the neem
      genome, of which 32,278 genes were expressed in neem tissues. Neem genome
      consists about 32.5% (87 Mb) of repetitive DNA elements. Neem tree is
      phylogenetically related to citrus, Citrus sinensis. Comparative analysis
      anchored 62% (161 Mb) of assembled neem genomic contigs onto citrus chromomes.
      Ultrahigh performance liquid chromatography-mass spectrometry-selected reaction
      monitoring (UHPLC-MS/SRM) method was used to quantify azadirachtin, nimbin, and
      salanin from neem tissues. Weighted Correlation Network Analysis (WCGNA) of
      expressed genes and metabolites resulted in identification of possible candidate
      genes involved in azadirachtin biosynthesis pathway. This study provides genomic,
      transcriptomic and quantity of top three neem metabolites resource, which will
      accelerate basic research in neem to understand biochemical pathways. 

PMID- 26290781
TI  - Correlates of condom use among female sex workers in The Gambia: results of a
      cross-sectional survey.
AB  - Objectives. This study examined correlates of condom use among 248 female sex
      workers (FSW) in The Gambia. Methods. Between July and August 2011, FSW in The
      Gambia who were older than 16 years of age, the age of consent in The Gambia,
      were recruited for the study using venue-based sampling and snowball sampling,
      beginning with seeds who were established clients with the Network of AIDS
      Services Organizations. To be eligible, FSW must have reported selling sex for
      money, favors, or goods in the past 12 months. Bivariate and multivariate
      logistic regressions were used to determine associations and the relative odds of
      the independent variables with condom use. Four different condom use dependent
      variables were used: consistent condom use in the past six months during vaginal
      or anal sex with all clients and partners; consistent condom use in the past
      month during vaginal sex with new clients; consistent condom use in the past
      month during vaginal sex with nonpaying partners (including boyfriends, husbands,
      or casual sexual partners); and condom use at last vaginal or anal sex with a
      nonpaying partner. Results. Many FSW (67.34%, n = 167) reported it was not at all
      difficult to negotiate condom use with clients in all applicable situations, and
      these FSW were more likely to report consistent condom use with all clients and
      partners in the past 6 months (aOR 3.47, 95% CI [1.70-7.07]) compared to those
      perceiving any difficulty in condom negotiation. In addition, FSW were more
      likely to report using condoms in the past month with new clients (aOR 8.04, 95%
      CI [2.11-30.65]) and in the past month with nonpaying partners (aOR 2.93, 95% CI
      [1.09-7.89]) if they had been tested for HIV in the past year. Women who bought
      all their condoms were less likely than those who received all of their condoms
      for free (aOR 0.38, 95% CI [0.15-0.97]) to have used a condom at last vaginal or
      anal sex with a nonpaying partner. Conclusions. HIV and sexually transmitted
      infection (STI) prevention interventions for FSW should aim to improve condom
      negotiation self-efficacy since women who report less difficulty negotiating
      condom use are more likely to use condoms with clients. Interventions should also
      be aimed at structural issues such as increasing access to free condoms and HIV
      testing since these were positively associated with condom use among FSW. 

PMID- 26290782
TI  - Allantoin ameliorates chemically-induced pancreatic beta-cell damage through
      activation of the imidazoline I3 receptors.
AB  - Objective. Allantoin is the primary active compound in yams (Dioscorea spp.).
      Recently, allantoin has been demonstrated to activate imidazoline 3 (I3)
      receptors located in pancreatic tissues. Thus, the present study aimed to
      investigate the role of allantoin in the effect to improve damage induced in
      pancreatic beta-cells by streptozotocin (STZ) via the I3 receptors. Research
      Design and Methods. The effect of allantoin on STZ-induced apoptosis in
      pancreatic beta-cells was examined using the ApoTox-Glo triplex assay, live/dead
      cell double staining assay, flow cytometric analysis, and Western blottings. The
      potential mechanism was investigated using KU14R: an I3 receptor antagonist, and
      U73122: a phospholipase C (PLC) inhibitor. The effects of allantoin on serum
      glucose and insulin secretion were measured in STZ-treated rats. Results.
      Allantoin attenuated apoptosis and cytotoxicity and increased the viability of
      STZ-induced beta-cells in a dose-dependent manner; this effect was suppressed by
      KU14R and U73112. Allantoin decreased the level of caspase-3 and increased the
      level of phosphorylated B-cell lymphoma 2 (Bcl-2) expression detected by Western
      blotting. The improvement in beta-cells viability was confirmed using flow
      cytometry analysis. Daily injection of allantoin for 8 days in STZ-treated rats
      significantly lowered plasma glucose and increased plasma insulin levels. This
      action was inhibited by treatment with KU14R. Conclusion. Allantoin ameliorates
      the damage of beta-cells induced by STZ. The blockade by pharmacological
      inhibitors indicated that allantoin can activate the I3 receptors through a PLC
      related pathway to decrease this damage. Therefore, allantoin and related analogs
      may be effective in the therapy for beta-cell damage. 

PMID- 26290783
TI  - Vision in two cyprinid fish: implications for collective behavior.
AB  - Many species of fish rely on their visual systems to interact with conspecifics
      and these interactions can lead to collective behavior. Individual-based models
      have been used to predict collective interactions; however, these models
      generally make simplistic assumptions about the sensory systems that are applied
      without proper empirical testing to different species. This could limit our
      ability to predict (and test empirically) collective behavior in species with
      very different sensory requirements. In this study, we characterized components
      of the visual system in two species of cyprinid fish known to engage in visually
      dependent collective interactions (zebrafish Danio rerio and golden shiner
      Notemigonus crysoleucas) and derived quantitative predictions about the
      positioning of individuals within schools. We found that both species had
      relatively narrow binocular and blind fields and wide visual coverage. However,
      golden shiners had more visual coverage in the vertical plane (binocular field
      extending behind the head) and higher visual acuity than zebrafish. The centers
      of acute vision (areae) of both species projected in the fronto-dorsal region of
      the visual field, but those of the zebrafish projected more dorsally than those
      of the golden shiner. Based on this visual sensory information, we predicted
      that: (a) predator detection time could be increased by >1,000% in zebrafish and
      >100% in golden shiners with an increase in nearest neighbor distance, (b)
      zebrafish schools would have a higher roughness value (surface area/volume ratio)
      than those of golden shiners, (c) and that nearest neighbor distance would vary
      from 8 to 20 cm to visually resolve conspecific striping patterns in both
      species. Overall, considering between-species differences in the sensory system
      of species exhibiting collective behavior could change the predictions about the
      positioning of individuals in the group as well as the shape of the school, which
      can have implications for group cohesion. We suggest that more effort should be
      invested in assessing the role of the sensory system in shaping local
      interactions driving collective behavior. 

PMID- 26290784
TI  - Awake fMRI reveals a specialized region in dog temporal cortex for face
      processing.
AB  - Recent behavioral evidence suggests that dogs, like humans and monkeys, are
      capable of visual face recognition. But do dogs also exhibit specialized cortical
      face regions similar to humans and monkeys? Using functional magnetic resonance
      imaging (fMRI) in six dogs trained to remain motionless during scanning without
      restraint or sedation, we found a region in the canine temporal lobe that
      responded significantly more to movies of human faces than to movies of everyday
      objects. Next, using a new stimulus set to investigate face selectivity in this
      predefined candidate dog face area, we found that this region responded similarly
      to images of human faces and dog faces, yet significantly more to both human and
      dog faces than to images of objects. Such face selectivity was not found in dog
      primary visual cortex. Taken together, these findings: (1) provide the first
      evidence for a face-selective region in the temporal cortex of dogs, which cannot
      be explained by simple low-level visual feature extraction; (2) reveal that
      neural machinery dedicated to face processing is not unique to primates; and (3)
      may help explain dogs' exquisite sensitivity to human social cues. 

PMID- 26290785
TI  - Whole genome sequencing enables the characterization of BurI, a LuxI homologue of
      Burkholderia cepacia strain GG4.
AB  - Quorum sensing is a mechanism for regulating proteobacterial gene expression in
      response to changes in cell population. In proteobacteria, N-acyl homoserine
      lactone (AHL) appears to be the most widely used signalling molecules in
      mediating, among others, the production of extracellular virulence factors for
      survival. In this work, the genome of B. cepacia strain GG4, a plasmid-free
      strain capable of AHL synthesis was explored. In silico analysis of the 6.6 Mb
      complete genome revealed the presence of a LuxI homologue which correspond to
      Type I quorum sensing. Here, we report the molecular cloning and characterization
      of this LuxI homologue, designated as BurI. This 609 bp gene was cloned and
      overexpressed in Escherichia coli BL21(DE3). The purified protein was
      approximately 25 kDa and is highly similar to several autoinducer proteins of the
      LuxI family among Burkholderia species. To verify the AHL synthesis activity of
      this protein, high resolution liquid chromatography-mass spectrometry analysis
      revealed the production of 3-oxo-hexanoylhomoserine lactone, N-octanoylhomoserine
      lactone and 3-hydroxy-octanoylhomoserine lactone from induced E. coli BL21
      harboring the recombinant BurI. Our data show, for the first time, the cloning
      and characterization of the LuxI homologue from B. cepacia strain GG4 and
      confirmation of its AHL synthesis activity. 

PMID- 26290786
TI  - Space-use, movement and dispersal of sub-adult cougars in a geographically
      isolated population.
AB  - Cougar (Puma concolor) observations have increased in Midwest North America, with
      breeding populations re-establishing in several regions east of their
      contemporary range. The Cypress Hills Uplands, located in southwest Saskatchewan
      and southeast Alberta, was recently re-colonized by cougars and now supports the
      easternmost confirmed breeding population of cougars in Canada. A number of
      factors contribute to this cougar range expansion, but it is dispersal that
      provides the mechanism for re-colonization of historic range. We used GPS-collar
      data to examine space-use and movement behavior of sub-adult cougars, the age
      class associated with dispersal, in the Cypress Hills. Conditional logistic
      regression and a two-stage modeling approach were used to estimate resource
      selection functions (RSF) of sub-adult cougars during two distinct ranging
      behaviors: transient movements (i.e., dispersal and exploratory forays) and
      localizing movements (i.e., temporary home ranges). Linear regression was used to
      model movement rates, measured as the distance between consecutive 3-h GPS
      relocations, of sub-adult cougars relative to different habitats, times of day
      and between transient and localizing behavior. All individual sub-adult cougars
      displayed bouts of transient and localizing behavior. All male cougars dispersed
      from their natal ranges and travelled considerably farther distances than female
      cougars. One male dispersed over 750 km eastward through the agricultural belt of
      northern Montana and southern Saskatchewan. Males occupied temporary home ranges
      in more open habitats on the fringes of the insular Cypress Hills, while females
      appeared to be recruited into the adult population, occupying treed habitat that
      provided more suitable cover. During both ranging behaviors, sub-adult cougars
      selected for rugged terrain and proximity to hydrological features (likely
      supporting riparian habitats) and avoided open cover types. Differences in
      habitat selection between ranging behaviors were observed in response to open
      water, roads and elevation. Although certain habitat characteristics were
      preferred, transient and localizing cougars used fast-paced nocturnal movements
      and shortened daytime movements when traversing open habitats to effectively
      limit their residency and exposure in less-suitable landscapes. Additionally,
      cougars moved greater distances at night during transient behavior compared to
      localizing behavior indicating cougars used cover of darkness to traverse novel
      terrain. In doing so, sub-adult cougars can successfully disperse several hundred
      kilometres across a matrix of open habitat in search of resources and mates. 

PMID- 26290787
TI  - Impact of copper toxicity on stone-head cabbage (Brassica oleracea var. capitata)
      in hydroponics.
AB  - Arable soils are frequently subjected to contamination with copper as the
      consequence of imbalanced fertilization with manure and organic fertilizers
      and/or extensive use of copper-containing fungicides. In the present study, the
      exposure of stone-head cabbage (Brassica oleracea var. capitata) to elevated
      Cu(2+) levels resulted in leaf chlorosis and lesser biomass yield at >=2 u M.
      Root nitrate content was not statistically affected by Cu(2+) levels, although it
      was substantially decreased at >=5 u M Cu(2+) in the shoot. The decrease in
      nitrate contents can be related to lower nitrate uptake rates because of growth
      inhibition by Cu-toxicity. Shoot sulfate content increased strongly at >=2 u M
      Cu(2+) indicating an increase in demand for sulfur under Cu stress. Furthermore,
      at >=2 uM concentration, concentration of water-soluble non-protein thiol
      increased markedly in the roots and to a smaller level in the shoot. When exposed
      to elevated concentrations of Cu(2+) the improved sulfate and water-soluble non
      protein thiols need further studies for the evaluation of their direct relation
      with the synthesis of metal-chelating compounds (i.e., phytochelatins). 

PMID- 26290788
TI  - Seasonal variation in microhabitat of salamanders: environmental variation or
      shift of habitat selection?
AB  - Relationships between species and their habitats are not always constant.
      Different processes may determine changes in species-habitat association:
      individuals may prefer different habitat typologies in different periods, or they
      may be forced to occupy a different habitat in order to follow the changing
      environment. The aim of our study was to assess whether cave salamanders change
      their habitat association pattern through the year, and to test whether such
      changes are determined by environmental changes or by changes in preferences. We
      monitored multiple caves in Central Italy through one year, and monthly measured
      biotic and abiotic features of microhabitat and recorded Italian cave salamanders
      distribution. We used mixed models and niche similarity tests to assess whether
      species-habitat relationships remain constant through the year. Microhabitat
      showed strong seasonal variation, with the highest variability in the superficial
      sectors. Salamanders were associated to relatively cold and humid sectors in
      summer, but not during winter. Such apparent shift in habitat preferences mostly
      occurred because the environmental gradient changed through the year, while
      individuals generally selected similar conditions. Nevertheless, juveniles were
      more tolerant to dry sectors during late winter, when food demand was highest.
      This suggests that tolerance for suboptimal abiotic conditions may change through
      time, depending on the required resources. Differences in habitat use are jointly
      determined by environmental variation through time, and by changes in the
      preferred habitat. The trade-offs between tolerance and resources requirement are
      major determinant of such variation. 

PMID- 26290789
TI  - Functional flexibility in wild bonobo vocal behaviour.
AB  - A shared principle in the evolution of language and the development of speech is
      the emergence of functional flexibility, the capacity of vocal signals to express
      a range of emotional states independently of context and biological function.
      Functional flexibility has recently been demonstrated in the vocalisations of pre
      linguistic human infants, which has been contrasted to the functionally fixed
      vocal behaviour of non-human primates. Here, we revisited the presumed chasm in
      functional flexibility between human and non-human primate vocal behaviour, with
      a study on our closest living primate relatives, the bonobo (Pan paniscus). We
      found that wild bonobos use a specific call type (the "peep") across a range of
      contexts that cover the full valence range (positive-neutral-negative) in much of
      their daily activities, including feeding, travel, rest, aggression, alarm,
      nesting and grooming. Peeps were produced in functionally flexible ways in some
      contexts, but not others. Crucially, calls did not vary acoustically between
      neutral and positive contexts, suggesting that recipients take pragmatic
      information into account to make inferences about call meaning. In comparison,
      peeps during negative contexts were acoustically distinct. Our data suggest that
      the capacity for functional flexibility has evolutionary roots that predate the
      evolution of human speech. We interpret this evidence as an example of an
      evolutionary early transition away from fixed vocal signalling towards functional
      flexibility. 

PMID- 26290791
TI  - On reconstructing Giraffa sivalensis, an extinct giraffid from the Siwalik Hills,
      India.
AB  - Giraffa sivalensis occurred during the Plio-Pleistocene period and probably
      represents the terminal species of the genus in Southern Asia. The holotype is an
      almost perfectly preserved cervical vertebra of disputed anatomical location.
      Although there is also uncertainty regarding this animal's size, other specimens
      that have been assigned to this species include fragments of two humeri, a
      radius, metacarpi and teeth. Here we estimate neck length, leg length and body
      mass using interspecific and, unusually, ontogenetic allometry of extant giraffe
      skeletal parameters. The appropriateness of each equation to estimate body mass
      was evaluated by calculating the prediction error incurred in both extant
      giraffes (G. camelopardalis) and okapis (Okapia johnstoni). It followed that the
      equations with the lowest prediction error in both species were considered robust
      enough to use in G. sivalensis. The size of G. sivalensis, based on the holotype,
      is proposed as 400 kg (range 228 kg-575 kg), with a neck length of approximately
      147 cm and a height of 390 cm. The molar lengths of tooth specimens considered
      agree with this size estimate. The humerus was the most appropriate long bone to
      establish body mass, which estimates a heavier animal of ca 790 kg. The
      discrepancy with the vertebral body weight estimate might indicate sexual
      dimorphism. Radial and metacarpal specimens estimate G. sivalensis to be as heavy
      as extant giraffes. This may indicate that the radius and metacarpus are
      unsuitable for body mass predictions in Giraffa spp. Alternatively, certain long
      bones may have belonged to another long legged giraffid that occurred during the
      same period and locality as G. sivalensis. We have concluded that if sexual
      dimorphism was present then males would have been about twice the size of
      females. If sexual dimorphism was not present and all bones were correctly
      attributed to this species, then G. sivalensis had a slender neck with a
      relatively stocky body. 

PMID- 26290790
TI  - Prey type and foraging ecology of Sanderlings Calidris alba in different climate
      zones: are tropical areas more favourable than temperate sites?
AB  - Sanderlings (Calidris alba) are long-distance migratory shorebirds with a non
      breeding range that spans temperate and tropical coastal habitats. Breeding in
      the High Arctic combined with non-breeding seasons in the tropics necessitate
      long migrations, which are energetically demanding. On an annual basis, the
      higher energy expenditures during migration might pay off if food availability in
      the tropics is higher than at temperate latitudes. We compared foraging behaviour
      of birds at a north temperate and a tropical non-breeding site in the Netherlands
      and Ghana, respectively. In both cases the birds used similar habitats (open
      beaches), and experienced similar periods of daylight, which enabled us to
      compare food abundance and availability, and behavioural time budgets and food
      intake. During the non-breeding season, Sanderlings in the Netherlands spent 79%
      of their day foraging; in Ghana birds spent only 38% of the daytime period
      foraging and the largest proportion of their time resting (58%). The main prey
      item in the Netherlands was the soft-bodied polychaete Scolelepis squamata, while
      Sanderlings in Ghana fed almost exclusively on the bivalve Donax pulchellus,
      which they swallowed whole and crushed internally. Average availability of
      polychaete worms in the Netherlands was 7.4 g ash free dry mass (AFDM) m(-2),
      which was one tenth of the 77.1 g AFDM m(-2) estimated for the beach in Ghana. In
      the tropical environment of Ghana the Sanderlings combined relatively low energy
      requirements with high prey intake rates (1.64 mg opposed to 0.13 mg AFDM s(-1)
      for Ghana and the Netherlands respectively). Although this may suggest that the
      Ghana beaches are the most favourable environment, processing the hard-shelled
      bivalve (D. pulchellus) which is the staple food could be costly. The large
      amount of daytime spent resting in Ghana may be indicative of the time needed to
      process the shell fragments, rather than indicate rest. 

PMID- 26290792
TI  - The 2014 coral bleaching and freshwater flood events in Kane'ohe Bay, Hawai'i.
AB  - Until recently, subtropical Hawai'i escaped the major bleaching events that have
      devastated many tropical regions, but the continued increases in global long-term
      mean temperatures and the apparent ending of the Pacific Decadal Oscillation
      (PDO) cool phase have increased the risk of bleaching events. Climate models and
      observations predict that bleaching in Hawai'i will occur with increasing
      frequency and increasing severity over future decades. A freshwater "kill" event
      occurred during July 2014 in the northern part of Kane'ohe Bay that reduced coral
      cover by 22.5% in the area directly impacted by flooding. A subsequent major
      bleaching event during September 2014 caused extensive coral bleaching and
      mortality throughout the bay and further reduced coral cover in the freshwater
      kill area by 60.0%. The high temperature bleaching event only caused a 1.0%
      reduction in live coral throughout the portion of the bay not directly impacted
      by the freshwater event. Thus, the combined impact of the low salinity event and
      the thermal bleaching event appears to be more than simply additive. The
      temperature regime during the September 2014 bleaching event was analogous in
      duration and intensity to that of the large bleaching event that occurred
      previously during August 1996, but resulted in a much larger area of bleaching
      and coral mortality. Apparently seasonal timing as well as duration and magnitude
      of heating is important. Coral spawning in the dominant coral species occurs
      early in the summer, so reservoirs of stored lipid in the corals had been
      depleted by spawning prior to the September 2014 event. Warm months above 27 
      degrees C result in lower coral growth and presumably could further decrease
      lipid reserves, leading to a bleaching event that was more severe than would have
      happened if the high temperatures occurred earlier in the summer. Hawaiian reef
      corals decrease skeletal growth at temperatures above 27  degrees C, so perhaps
      the "stress period" actually started long before the bleaching threshold of 29 
      degrees C was reached. Hawai'i is directly influenced by the PDO which may become
      a factor influencing bleaching events in subtropical Hawai'i in much the same
      manner as variations in the El Nino Southern Oscillation (ENSO) influences
      bleaching events at low latitudes in the tropical Pacific. Records show that
      offshore temperatures measured by satellite will not always predict inshore
      bleaching because other factors (high cloud cover, high wind and wave action,
      tidal exchange rate) can limit inshore heating and prevent temperatures in the
      bay from reaching the bleaching threshold. Low light levels due to cloud cover or
      high turbidity can also serve to prevent bleaching. 

PMID- 26290793
TI  - Assessing the reproducibility of discriminant function analyses.
AB  - Data are the foundation of empirical research, yet all too often the datasets
      underlying published papers are unavailable, incorrect, or poorly curated. This
      is a serious issue, because future researchers are then unable to validate
      published results or reuse data to explore new ideas and hypotheses. Even if data
      files are securely stored and accessible, they must also be accompanied by
      accurate labels and identifiers. To assess how often problems with metadata or
      data curation affect the reproducibility of published results, we attempted to
      reproduce Discriminant Function Analyses (DFAs) from the field of organismal
      biology. DFA is a commonly used statistical analysis that has changed little
      since its inception almost eight decades ago, and therefore provides an
      opportunity to test reproducibility among datasets of varying ages. Out of 100
      papers we initially surveyed, fourteen were excluded because they did not present
      the common types of quantitative result from their DFA or gave insufficient
      details of their DFA. Of the remaining 86 datasets, there were 15 cases for which
      we were unable to confidently relate the dataset we received to the one used in
      the published analysis. The reasons ranged from incomprehensible or absent
      variable labels, the DFA being performed on an unspecified subset of the data, or
      the dataset we received being incomplete. We focused on reproducing three common
      summary statistics from DFAs: the percent variance explained, the percentage
      correctly assigned and the largest discriminant function coefficient. The
      reproducibility of the first two was fairly high (20 of 26, and 44 of 60
      datasets, respectively), whereas our success rate with the discriminant function
      coefficients was lower (15 of 26 datasets). When considering all three summary
      statistics, we were able to completely reproduce 46 (65%) of 71 datasets. While
      our results show that a majority of studies are reproducible, they highlight the
      fact that many studies still are not the carefully curated research that the
      scientific community and public expects. 

PMID- 26290794
TI  - Variation in phenology of hibernation and reproduction in the endangered New
      Mexico meadow jumping mouse (Zapus hudsonius luteus).
AB  - Hibernation is a key life history feature that can impact many other crucial
      aspects of a species' biology, such as its survival and reproduction. I examined
      the timing of hibernation and reproduction in the federally endangered New Mexico
      meadow jumping mouse (Zapus hudsonius luteus), which occurs across a broad range
      of latitudes and elevations in the American Southwest. Data from museum specimens
      and field studies supported predictions for later emergence and shorter active
      intervals in montane populations relative to lower elevation valley populations.
      A low-elevation population located at Bosque del Apache National Wildlife Refuge
      (BANWR) in the Rio Grande valley was most similar to other subspecies of Z.
      hudsonius: the first emergence date was in mid-May and there was an active
      interval of 162 days. In montane populations of Z. h. luteus, the date of first
      emergence was delayed until mid-June and the active interval was reduced to ca
      124-135 days, similar to some populations of the western jumping mouse (Z.
      princeps). Last date of immergence into hibernation occurred at about the same
      time in all populations (mid to late October). In montane populations pregnant
      females are known from July to late August and evidence suggests that they have a
      single litter per year. At BANWR two peaks in reproduction were expected based on
      similarity of active season to Z. h. preblei. However, only one peak was clearly
      evident, possibly due to later first reproduction and possible torpor during late
      summer. At BANWR pregnant females are known from June and July. Due to the short
      activity season and geographic variation in phenology of key life history events
      of Z. h. luteus, recommendations are made for the appropriate timing for surveys
      for this endangered species. 

PMID- 26290795
TI  - Remote sensing captures varying temporal patterns of vegetation between human
      altered and natural landscapes.
AB  - Global change has led to shifts in phenology, potentially disrupting species
      interactions such as plant-pollinator relationships. Advances in remote sensing
      techniques allow one to detect vegetation phenological diversity between
      different land use types, but it is not clear how this translates to other
      communities in the ecosystem. Here, we investigated the phenological diversity of
      the vegetation across a human-altered landscape including urban, agricultural,
      and natural land use types. We found that the patterns of change in the
      vegetation indices (EVI and NDVI) of human-altered landscapes are out of
      synchronization with the phenology in neighboring natural California grassland
      habitat. Comparing these findings to a spatio-temporal pollinator distribution
      dataset, EVI and NDVI were significant predictors of total bee abundance, a
      relationship that improved with time lags. This evidence supports the importance
      of differences in temporal dynamics between land use types. These findings also
      highlight the potential to utilize remote sensing data to make predictions for
      components of biodiversity that have tight vegetation associations, such as
      pollinators. 

PMID- 26290796
TI  - (210)Po microsphere radiological design for tumor vascular disruption.
AB  - The feasibility of disrupting a tumor's vascular structure using (210)Po
      microspheres is investigated using standard ion and photon absorbed dose
      methodologies. Calculated absorbed dose profiles for (210)Po alpha particles are
      sufficient to disrupt a tumor's arteriole structure while minimizing the dose
      outside the blood vessel wall. (210)Po photons contribute minimal dose to healthy
      tissue. The requisite activity of (210)Po to facilitate vascular disruption is
      calculated. 

PMID- 26290797
TI  - Field-measured drag area is a key correlate of level cycling time trial
      performance.
AB  - Drag area (Ad ) is a primary factor determining aerodynamic resistance during
      level cycling and is therefore a key determinant of level time trial performance.
      However, Ad has traditionally been difficult to measure. Our purpose was to
      determine the value of adding field-measured Ad as a correlate of level cycling
      time trial performance. In the field, 19 male cyclists performed a level (22.1
      km) time trial. Separately, field-determined Ad and rolling resistance were
      calculated for subjects along with projected frontal area assessed directly (AP )
      and indirectly (Est AP ). Also, a graded exercise test was performed to determine
      [Formula: see text] peak, lactate threshold (LT), and economy. [Formula: see
      text] peak ([Formula: see text]) and power at LT were significantly correlated to
      power measured during the time trial (r = 0.83 and 0.69, respectively) but were
      not significantly correlated to performance time (r = - 0.42 and -0.45). The
      correlation with performance time improved significantly (p < 0.05) when these
      variables were normalized to Ad . Of note, Ad alone was better correlated to
      performance time (r = 0.85, p < 0.001) than any combination of non-normalized
      physiological measure. The best correlate with performance time was field
      measured power output during the time trial normalized to Ad (r = - 0.92). AP
      only accounted for 54% of the variability in Ad . Accordingly, the correlation to
      performance time was significantly lower using power normalized to AP (r = -
      0.75) or Est AP (r = - 0.71). In conclusion, unless normalized to Ad , level time
      trial performance in the field was not highly correlated to common laboratory
      measures. Furthermore, our field-measured Ad is easy to determine and was the
      single best predictor of level time trial performance. 

PMID- 26290798
TI  - Characteristics of ambulatory care visits to family medicine specialists in
      Taiwan: a nationwide analysis.
AB  - Although family medicine (FM) is the most commonly practiced specialty among all
      the medical specialties, its practice patterns have seldom been analyzed. Looking
      at data from Taiwan's National Health Insurance Research Database, the current
      study analyzed ambulatory visits to FM specialists nationwide. From a sample
      dataset that randomly sampled one out of every 500 cases among a total of
      309,880,000 visits in 2012, it was found that 18.8% (n = 116, 551) of the 619,760
      visits in the dataset were made to FM specialists. Most of the FM services were
      performed by male FM physicians. Elderly patients above 80 years of age accounted
      for only 7.1% of FM visits. The most frequent diagnoses (22.8%) were associated
      acute upper respiratory infections (including ICD 460, 465 and 466). Anti
      histamine agents were prescribed in 25.6% of FM visits. Hypertension, diabetes
      and dyslipidemia were the causes of 20.7% of the ambulatory visits made to FM
      specialists of all types, while those conditions accounted for only 10.6% of
      visits to FM clinics. The study demonstrated the relatively low proportion of
      chronic diseases that was managed in FM clinics in Taiwan, and our detailed
      results could contribute to evidence-based discussions on healthcare policymaking
      and residency training. 

PMID- 26290799
TI  - Rapid eye movement-sleep is reduced in patients with acute uncomplicated
      diverticulitis-an observational study.
AB  - Introduction. Sleep disturbances are commonly found in patients in the
      postoperative period. Sleep disturbances may give rise to several complications
      including cardiopulmonary instability, transient cognitive dysfunction and
      prolonged convalescence. Many factors including host inflammatory responses are
      believed to cause postoperative sleep disturbances, as inflammatory responses can
      alter sleep architecture through cytokine-brain interactions. Our aim was to
      investigate alteration of sleep architecture during acute infection and its
      relationships to inflammation and clinical symptoms. Materials & Methods. In this
      observational study, we included patients with acute uncomplicated diverticulitis
      as a model to investigate the isolated effects of inflammatory responses on
      sleep. Eleven patients completed the study. Patients were admitted and treated
      with antibiotics for two nights, during which study endpoints were measured by
      polysomnography recordings, self-reported discomfort scores and blood samples of
      cytokines. One month later, the patients, who now were in complete remission,
      were readmitted and the endpoints were re-measured (the baseline values).
      Results. Total sleep time was reduced 4% and 7% the first (p = 0.006) and second
      (p = 0.014) nights of diverticulitis, compared to baseline, respectively. The
      rapid eye movement sleep was reduced 33% the first night (p = 0.016), compared to
      baseline. Moreover, plasma IL-6 levels were correlated to non-rapid eye movement
      sleep, rapid eye movement sleep and fatigue. Conclusion. Total sleep time and
      rapid eye movement sleep were reduced during nights with active diverticulitis
      and correlated with markers of inflammation. 

PMID- 26290800
TI  - To beat or not to beat a tick: comparison of DNA extraction methods for ticks
      (Ixodes scapularis).
AB  - Background. Blacklegged ticks (Ixodes scapularis) are important disease vectors
      in the United States, known to transmit a variety of pathogens to humans,
      including bacteria, protozoa, and viruses. Their importance as a disease vector
      necessitates reliable and comparable methods for extracting microbial DNA from
      ticks. Furthermore, to explore the population genetics or genomics of this tick,
      appropriate DNA extraction techniques are needed for both the vector and its
      microbes. Although a few studies have investigated different methods of DNA
      isolation from ticks, they are limited in the number and types of DNA extraction
      and lack species-specific quantification of DNA yield. Methods. Here we
      determined the most efficient and consistent method of DNA extraction from two
      different developmental stages of I. scapularis-nymph and adult-that are the most
      important for disease transmission. We used various methods of physical
      disruption of the hard, chitinous exoskeleton, as well as commercial and non
      commercial DNA isolation kits. To gauge the effectiveness of these methods, we
      quantified the DNA yield and confirmed the DNA quality via PCR of both tick and
      microbial genetic material. Results. DNA extraction using the Thermo GeneJET
      Genomic DNA Purification Kit resulted in the highest DNA yields and the most
      consistent PCR amplification when combined with either cutting or bead beating
      with select matrices across life stages. DNA isolation methods using ammonium
      hydroxide as well as the MoBio PowerSoil kit also produced strong and successful
      PCR amplification, but only for females. Discussion. We contrasted a variety of
      readily available methods of DNA extraction from single individual blacklegged
      ticks and presented the results through a quantitative and qualitative
      assessment. 

PMID- 26290801
TI  - No evidence that presence of sexually transmitted infection selects for reduced
      mating rate in the two spot ladybird, Adalia bipunctata.
AB  - Sexually transmitted infections (STIs) are common in animals and plants, and
      frequently impair individual fertility. Theory predicts that natural selection
      will favour behaviours that reduce the chance of acquiring a STI. We investigated
      whether an STI, Coccipolipus hippodamiae has selected for increased rejection of
      mating by female Adalia bipunctata as a mechanism to avoid exposure. We first
      demonstrated that rejection of mating by females did indeed reduce the chance of
      acquiring the mite. We then examined whether rejection rate and mating rate
      differed between ladybirds from mite-present and mite-absent populations when
      tested in a common environment. No differences in rejection intensity or remating
      propensity were observed between the two populations. We therefore conclude there
      is no evidence that STIs have driven the evolution of female mating behaviour in
      this species. 

PMID- 26290802
TI  - Selection in the dopamine receptor 2 gene: a candidate SNP study.
AB  - Dopamine is a major neurotransmitter in the human brain and is associated with
      various diseases. Schizophrenia, for example, is treated by blocking the dopamine
      receptors type 2. Shaner, Miller & Mintz (2004) stated that schizophrenia was the
      low fitness variant of a highly variable mental trait. We therefore explore
      whether the dopamine receptor 2 gene (DRD2) underwent any selection processes. We
      acquired genotype data of the 1,000 Genomes project (phase I), which contains
      1,093 individuals from 14 populations. We included single nucleotide
      polymorphisms (SNPs) with two minor allele frequencies (MAFs) in the analysis:
      MAF over 0.05 and over 0.01. This is equivalent to 151 SNPs (MAF > 0.05) and 246
      SNPs (MAF > 0.01) for DRD2. We used two different approaches (an outlier approach
      and a Bayesian approach) to detect loci under selection. The combined results of
      both approaches yielded nine (MAF > 0.05) and two candidate SNPs (MAF > 0.01),
      under balancing selection. We also found weak signs for directional selection on
      DRD2, but in our opinion these were too weak to draw any final conclusions on
      directional selection in DRD2. All candidates for balancing selection are in the
      intronic region of the gene and only one (rs12574471) has been mentioned in the
      literature. Two of our candidate SNPs are located in specific regions of the
      gene: rs80215768 lies within a promoter flanking region and rs74751335 lies
      within a transcription factor binding site. We strongly encourage research on our
      candidate SNPs and their possible effects. 

PMID- 26290803
TI  - Characterization of mature maize (Zea mays L.) root system architecture and
      complexity in a diverse set of Ex-PVP inbreds and hybrids.
AB  - The mature root system is a vital plant organ, which is critical to plant
      performance. Commercial maize (Zea mays L.) breeding has resulted in a steady
      increase in plant performance over time, along with noticeable changes in above
      ground vegetative traits, but the corresponding changes in the root system are
      not presently known. In this study, roughly 2500 core root systems from field
      trials of a set of 10 diverse elite inbreds formerly protected by Plant Variety
      Protection plus B73 and Mo17 and the 66 diallel intercrosses among them were
      evaluated for root traits using high throughput image-based phenotyping. Overall
      root architecture was modeled by root angle (RA) and stem diameter (SD), while
      root complexity, the amount of root branching, was quantified using fractal
      analysis to obtain values for fractal dimension (FD) and fractal abundance (FA).
      For each trait, per se line effects were highly significant and the most
      important contributor to trait performance. Mid-parent heterosis and specific
      combining ability was also highly significant for FD, FA, and RA, while none of
      the traits showed significant general combining ability. The interaction between
      the environment and the additive line effect was also significant for all traits.
      Within the inbred and hybrid generations, FD and FA were highly correlated (rp >=
      0.74), SD was moderately correlated to FD and FA (0.69 >= rp >= 0.48), while the
      correlation between RA and other traits was low (0.13 >= rp >= -0.40). Inbreds
      with contrasting effects on complexity and architecture traits were observed,
      suggesting that root complexity and architecture traits are inherited
      independently. A more comprehensive understanding of the maize root system and
      the way it interacts with the environment will be useful for defining adaptation
      to nutrient acquisition and tolerance to stress from drought and high plant
      densities, critical factors in the yield gains of modern hybrids. 

PMID- 26290804
TI  - Tamoxifen-induced ovarian hyperstimulation during premenopausal hormonal therapy
      for breast cancer in Japanese women.
AB  - PURPOSE: Tamoxifen is an anti-estrogenic drug that is widely used for endocrine
      dependent breast cancer as adjuvant hormonal therapy, and its use has been
      reported to be frequently associated with high levels of serum estradiol. Since
      the population of premenopausal women receiving tamoxifen therapy is growing in
      Japan, we retrospectively analyzed the incidence of ovarian hyperstimulation by
      tamoxifen therapy in Japanese women. METHODS: Eleven patients who received
      surgical therapy for endocrine-dependent breast cancer and showed high values of
      serum estradiol during post-operative tamoxifen therapy were recruited in this
      study and evaluated by examining the serum concentration of follicular
      stimulating hormone (FSH) and follicular development. RESULTS: The mean age,
      serum concentrations of estradiol and FSH, and follicular diameter were 41.3
      years old, 1015.8 pg/mL, 11.8 mIU/mL, and 3.47 cm, respectively. In 6 cases,
      multiple follicular development was observed, while the other cases showed single
      follicular development with a mean serum estradiol level of 848.6 pg/mL and
      follicular diameter of 4.46 cm. There was no significant difference in age or FSH
      concentration between the two groups. The mean periods from the start of the
      single administration of tamoxifen to the initial detection of a high estradiol
      concentration was 716.5 days. CONCLUSIONS: These findings indicate that tamoxifen
      could stimulate the ovarian function even after 2-year treatment. Since single
      and multiple follicular developments with large sizes were observed, dual
      mechanisms through the inhibition of both negative and positive feedback to the
      hypothalamic-pituitary-axis can be proposed to explain the adverse effects of
      tamoxifen on ovarian function.

PMID- 26290805
TI  - Anomalous origin and aneurysm of the right coronary artery associated with
      congenital bicuspid aortic valve: MDCT findings.
AB  - Anomalous origin of the coronary artery taking an interarterial course can cause
      myocardial infarction or sudden death. Association of anomalous origin of the
      coronary artery with congenital bicuspid aortic valve is rare, and only a few
      cases have been reported with imaging findings. Coronary artery aneurysms found
      in young adults are usually non-atherosclerotic. We report MDCT findings of
      anomalous origin and aneurysm of the right coronary artery associated with
      congenital bicuspid aortic valve in a 33-year-old man with a history of Kawasaki
      disease in the childhood, and the key role of MDCT in exact diagnosis and
      successful management of the complicated disease. 

PMID- 26290806
TI  - Probabilistic Voxel-Fe model for single cell motility in 3D.
AB  - BACKGROUND: Cells respond to a variety of external stimuli regulated by the
      environment conditions. Mechanical, chemical and biological factors are of great
      interest and have been deeply studied. Furthermore, mathematical and
      computational models have been rapidly growing over the past few years,
      permitting researches to run complex scenarios saving time and resources. Usually
      these models focus on specific features of cell migration, making them only
      suitable to study restricted phenomena. METHODS: Here we present a versatile
      finite element (FE) cell-scale 3D migration model based on probabilities
      depending in turn on ECM mechanical properties, chemical, fluid and boundary
      conditions. RESULTS: With this approach we are able to capture important outcomes
      of cell migration such as: velocities, trajectories, cell shape and aspect ratio,
      cell stress or ECM displacements. CONCLUSIONS: The modular form of the model will
      allow us to constantly update and redefine it as advancements are made in
      clarifying how cellular events take place.

PMID- 26290807
TI  - The role of rapid diagnostic tests in managing adults with pneumonia in low
      resource settings.
AB  - In well-resourced settings the systematic use of rapid diagnostics tests (e.g.
      pneumococcal urinary antigen test) that define the causal pathogen to direct
      therapy has not resulted in significantly improved outcomes in adults with
      pneumonia. The management of pneumonia in many low-resource settings is
      complicated by a substantial burden of tuberculosis and HIV-associated
      opportunistic infections, in addition to the usual spectrum of pathogens seen in
      well-resourced settings. Clinical features alone do not reliably distinguish
      between these different aetiologies and physicians often have to treat
      empirically. Given the limitations in diagnostic laboratory capability present in
      most low-resource settings, rapid and point-of-care diagnostic tests could become
      valuable tools to guide treatment decisions. Pneumococcal and Legionella urinary
      antigen tests are specific and moderately sensitive, but their utility in low
      resource settings is uncertain. The Cepheid Xpert MTB/RIF platform and rapid
      assays for urinary lipoarabinomannan can substantially speed up tuberculosis
      diagnosis; the current challenge is to translate this into earlier treatment and
      hopefully improve patient outcome. In HIV-infected patients, 1-3-beta-D-glucan is
      a serum marker of Pneumocystis jirovecii infection with excellent sensitivity.
      Further studies are needed to assess the clinical utility and cost-effectiveness
      of these rapid diagnostics assays when they incorporated into treatment
      algorithms.

PMID- 26290808
TI  - When there is Confusion and Conflicts - Ask Delphi!

PMID- 26290809
TI  - Journal of Neonatal Surgery: Now on PubMed.

PMID- 26290811
TI  - Anorectal Malformations (Part 3).

PMID- 26290810
TI  - Early Closure of Gastroschisis After Silo Placement Correlates with Earlier
      Enteral Feeding.
AB  - OBJECTIVES: Gastroschisis is a congenital anomaly affecting 2.3-4.4/10,000
      births. Previous studies show initiation of early enteral feeds predicts improved
      outcomes. We hypothesize that earlier definitive closure after silo placement;
      can lead to earlier enteral feed initiation. Design/ Setting/ Duration:
      Retrospective review of patients with gastroschisis from 2005 and 2014 at a
      single institution. MATERIAL AND METHODS: The data, including ethnicity,
      gestational age, birth weight, time to definitive closure, and time of first and
      full feeds, were analyzed using both Spearman's rho and the Kruskal-Wallis rank
      sum test where appropriate; a p value less than 0.05 was considered significant.
      RESULTS: Forty-three patients (24 males, 19 females) born with gastroschisis were
      identified. Overall survival rate was 88% (38/43). Forty of the 43 patients had a
      silo placed prior to definitive closure. Median days to closure were 6 (0 to 85)
      days. First feeds on average began on day of life (DOL) 17, and full feeds on DOL
      25. Earlier closure of gastroschisis correlated with early initiation of feeds
      (p=0.0001) and shorter time to full feeds (p=0.018), closure by DOL4 showed a
      trend toward earlier feeding (p=0.13). CONCLUSION: Earlier closure of
      gastroschisis after silo placement was associated with earlier feed initiation
      and shorter time to full feeds.

PMID- 26290812
TI  - Congenital CSF Rhinorrhoea sans Encephalocoele, sans Trauma, sans Tumour.
AB  - The authors describe a case of cerebrospinal fluid rhinorrhea due to a congenital
      defect in cribriform plate, an anomaly that has not been described hitherto. It
      was successfully treated surgically. 

PMID- 26290813
TI  - Thoracoscopic Patch Repair of Congenital Diaphragmatic Hernia in a Neonate using
      Spiral Tacks: A Case Report.
AB  - We present a case of congenital diaphragmatic hernia that was successfully
      treated with spi-ral tacks using thoracoscopy. A newborn female was diagnosed
      with a diaphragmatic hernia at 20 weeks of gestation. The defect was surgically
      repaired by thoracoscopy and primary closure. On postoperative day 25, she
      developed respiratory distress. Chest x-ray showed a recurrence and was taken to
      the OR for surgical repair with spiral tacks. 

PMID- 26290814
TI  - Infantile Hypertrophic Pyloric Stenosis in Postoperative Esophageal Atresia with
      Tracheoesophageal Fistula.
AB  - Development of infantile hypertrophic pyloric stenosis during postoperative
      period in EA with TEF is rare. Postoperative vomiting or feeding intolerance in
      EA is more common which is due to esophageal stricture, gastroesophageal reflux
      and esophageal dysmotility. A typical case of IHPS also presents with non-bilious
      projectile vomiting at around 3-4 weeks of life. The diagnosis of infantile
      hypertrophic pyloric stenosis in this subset is usually delayed because of its
      rarity. We report a case of IHPS in postoperative EA and emphasize on high index
      of suspicion to avoid any delay in diagnosis with its metabolic consequences. 

PMID- 26290815
TI  - Sacrococcygeal Teratoma with Yolk Sac Component in a Neonate.
AB  - Sacrococcygeal teratoma (SCT) is the most common congenital tumor in neonates.
      SCT may be benign (mature and immature) or malignant. Malignancy is rare in SCT
      diagnosed before 2 months of age. Here, we describe a neonate having a mature
      teratoma with a focus of malignant yolk sac tumor within and the difficulties
      faced in its management. 

PMID- 26290816
TI  - Two Cases of Neonatal Gastric Perforation.

PMID- 26290817
TI  - Thoracoscopic Plication for Bilateral Eventration of Diaphragm in a Neonate.

PMID- 26290818
TI  - Large Hernia of Umbilical Cord Misdiagnosed as Omphalocele.

PMID- 26290819
TI  - Reverse Tissue Expansion in Gastroschisis: What to do if the Defect is too large
      to close after Silo Removal?

PMID- 26290820
TI  - Teaching Anorectal Malformations.

PMID- 26290821
TI  - Reply: Teaching Anorectal Malformations.

PMID- 26290822
TI  - Forearm Injury Associated with Compound Presentation and Prolonged Labour.

PMID- 26290824
TI  - Feasibility of Internet-based Post-secondary Nutrition Education: Incorporating
      Features of the Mediterranean Diet.
AB  - BACKGROUND: The Internet continues to serve as an ideal venue for health
      education interventions promoting behavior change. Due to the progressive
      expansion in online education programs, new methodologies that contribute across
      health education and program planning continuums are needed. METHODS: This
      ecologic study investigated the change in student dietary behav-ior and food
      choices following an original online education intervention that introduced the
      Mediterranean diet (MD) in a community college in Houston, Texas. A non
      probability convenience sample (n=65) provided pretest-posttest data measuring
      knowledge of and attitudes toward the MD. The intervention was incorporated into
      an undergraduate nutrition course, delivered entirely online and evaluated using
      the Mediterranean Diet Quality Index (KIDMED) survey. RESULTS: The intervention
      improved total participant population from a mean KIDMED score of poor (4.12) to
      a mean score of high (8.45) indicating an increase in knowledge of MD dietary
      guidelines and a positive shift in favorable attitude, particularly among men.
      CONCLUSION: This study provides a unique pedagogical illustration of online learn
      ing that introduce a specific evidence-based dietary guideline to a college
      student population. A detailed discussion of findings and lessons learned is
      provided.

PMID- 26290823
TI  - Tobacco Use Prevention by Integrating Inside and Outside of School Based
      Programs: A Systematic Review Article.
AB  - BACKGROUND: Experience of tobacco use in early ages will increase probability of
      addiction to nicotine therefore, efficient tobacco control programs for teenagers
      are crucial. This study was conducted to recognize elements of successful
      integrated inside and outside of school based smoking prevention programs.
      METHODS: MeSH terms and related keywords were used to search PubMed, Cochrane,
      Medline, EMBASE, ERIC, SID databases from inception to 29th October 2013. Trials
      with random and non-random designs, systematic reviews and cohort studies that
      assessed or reported application of integrated tobacco control programs were
      included. Quality of the retrieved publications was checked independently by the
      authors and any disagreement was resolved by consensus. RESULT: Among the 745
      identified publications, only 15 studies had the inclusion criteria with a
      considerable methodological heterogeneity. While, precise out-come of integrated
      out of school/school-based interventions were not percepti-ble but this study's
      findings implied that outside of school intervention could strengthen school
      based tobacco prevention programs. No study was found to examine school-based
      interventions integrated with primary health care such as anti-tobacco
      consultations, high-risk students screening and their referral to special
      centers. CONCLUSION: Integration of outside and inside of school-based programs
      may boost probability of obtaining favorable outcomes and success rate in
      practice.

PMID- 26290825
TI  - Evaluation of the Iranian Mini Nutritional Assessment Short-Form in Community
      dwelling Elderly.
AB  - BACKGROUND: This study was aimed to assess agreement and diagnostic accuracy of
      the Iranian version of Mini Nutritional Assessment short-form (MNA-SF) against
      the original MNA, as a gold standard in community-dwelling elderly. METHODS: The
      full MNA and 9-item MNA-SF comprising questions regarding clinical status,
      dietary assessment and self-perception of health status and nutri-tion together
      with mid-arm and calf circumference measurements without in-cluding the body mass
      index (BMI) were completed for 205 volunteers aged 65 or older recruited from all
      over Markazi Province (Iran). Correlation, diagnostic accuracy and agreement
      between the MNA-SF and full MNA were calculated. RESULTS: The MNA and the MNA-SF
      classified 45.4% and 64.4% of the sub-jects as malnourished or at risk of
      malnutrition, respectively. Substantial agree-ment between the MNA-SF and full
      MNA was observed (Kappa=0.633). The MNA-SF correlated strongly with the full MNA
      (r=0.868, P<0.001). The MNA-SF showed high sensitivity (96.77%) and negative
      predictive values (95.89%), relatively high specificity (62.5%) and positive
      predictive values (68.18%) and fair accuracy (Area under curve =0.796).
      CONCLUSION: Iranian MNA-SF seems to be an applicable screening tool for quick
      detection of malnutrition or at risk of malnutrition in community-dwelling
      elderly especially when BMI is unavailable.

PMID- 26290826
TI  - Promoting Evidence to Policy Link on the Control of Infectious Diseases of
      Poverty in Nigeria: Outcome of A Multi-Stakeholders Policy Dialogue.
AB  - BACKGROUND: In Nigeria, malaria, schistosomiasis and lymphatic filariasis are
      among infectious diseases of poverty (IDP) with severe health burden and require
      effective policy strategies for their control. In this study, we investigated the
      value of policy brief and policy dialogue as excellent policymaking mechanisms
      that enable policymakers to adapt effective evidence informed policy for IDP
      control. METHODS: A policy brief was developed on the control of malaria,
      schistosomiasis and lymphatic filariasis and subjected to deliberations in a one
      day multi-stakeholder policy dialogue held in Ebonyi State Nigeria. A modified
      cross sectional intervention study design was used in this investigation.
      Structured pre-tested questionnaires were used to evaluate the policy brief
      document and policy dialogue process at the end of the policy dialogue. RESULTS:
      Forty-seven policymakers participated in the dialogue. An analysis of the
      response on the policy brief regarding context, different features of the
      problem; policy options and key implementation considerations indicated the mean
      ratings (MNRs) mostly ranged from 6.40-6.85 on 7 point scale. The over-all
      assessment of the policy brief had MNR at 6.54. The analysis of the response on
      the policy dialogue regarding the level of priority of policy issue, opportunity
      to discuss different features of the problem and options for addressing the
      problem, and the MNRs mostly ranged from 6.50-6.82. The overall assessment of the
      policy dialogue had MNR at 6.72. CONCLUSION: Policy dialogues can allow research
      evidence to be considered together with views, experiences and tacit knowledge of
      policymakers and can enhance evidence-to-policy link.

PMID- 26290827
TI  - Healthy Diet and Nutrition Education Program among Women of Reproductive Age: A
      Necessity of Multilevel Strategies or Community Responsibility.
AB  - BACKGROUND: Reproductive years represent a major proportion of women"s life. This
      review focuses on recommended nutritional considerations, physical activity
      pattern as well as the effect of nutrition education (NE) on behavior
      modification and health outcomes of women of reproductive age using either single
      level, multiple-level or community-level interventions. METHODS: For this
      narrative review, numerous searches were conducted on databases of PubMed,
      Science Direct and Google Scholar search engine using the keywords women,
      reproductive age, NE, interventions, community-based. RESULTS: Even though single
      intervention is effective, multiple intervention programmes in addition to
      behavior modification components are even more successful in terms of modified
      behaviors and health outcomes. Moreover, community based interventions using
      multilevel strategies are further useful for improved health outcomes and
      behavior modification. CONCLUSION: NE programmes have been effective in positive
      behavior modification measured in terms of eating pattern and health quality.
      Thus, it is recommended that health professionals use multiple intervention
      strategies at community level to ensure improved outcomes. Political support is
      also required to create culturally sensitive methods of delivering nutritional
      programmes. Finally, as policy is dependent on program cost, nutritional
      programmes need to combine methods of cost analysis to show cost effectiveness of
      supplying adequate nutrition for women throughout the lifecycle.

PMID- 26290828
TI  - Validity, Reliability and Feasibility of the Eating Behavior Pattern
      Questionnaire (EBPQ) among Iranian Female Students.
AB  - BACKGROUND: The aim of this study was to assess the validity, reliability and
      feasibility of eating behavior pattern questionnaire (EBPQ) in female university
      students. METHODS: In this study, after forward-backward translation, the
      questionnaire was reviewed by a panel of nutritionists and a psychologist and
      further thirty participants for the content validity measurement. The translated
      and modified questionnaire was completed by 225 female students of Tabriz
      University in 2013. Principle axis factoring, confirmatory factor analysis and
      known group analysis were conducted for construct, convergent and discriminant
      validity. Internal consistency and test-retest reliability were assessed by
      Cronbach's alpha coefficient and intra-class correlation coefficient (ICC).
      Ceiling and floor effects were also performed for evaluating the feasibility of
      the instrument. RESULTS: By using exploratory factor analysis, nine factors were
      extracted. Confirmatory factor analysis confirmed the convergent validity.
      Cronbach 's alphaand ICC were ranged between 0.55 to 0.78 and 0.67 to 0.89,
      respectively. The significant difference for some three subscales between
      diabetes and healthy subjects determined the discriminant validity. No ceiling
      and floor effects were found. CONCLUSION: Our findings demonstrate the initial
      validity, reliability and feasibility of the Iranian version of EBPQ as a useful
      tool for eating behavior studies in young females.

PMID- 26290829
TI  - Determinants of Cancer Early Detection Behaviors:Application of Protection
      Motivation Theory.
AB  - BACKGROUND: Cancer is account for 13% of all deaths around the world and is the
      third cause of mortality in Iran. More than one third of these cases are pre
      ventable and about 33% are curable with early detection. The aim of this study
      was to determine the predictors of cancer early detection (CED) behaviors
      applying Protection Motivation Theory (PMT). METHODS: In this cross-sectional
      study, cluster sampling method was employed to recruit 260 individuals of above
      20 years old in Yazd, Iran and a researcher designed questionnaire was completed
      through interviews for each of the respondents. PMT theoretical variables and CED
      behaviors were the basis of data collection procedure. RESULTS: Participants
      acquired 64.47% of the protection motivation, 30.97% of the passive and 45.64% of
      the active behaviors" possible scores. Theory constructs predicted 19.8%, 15.6%
      and 9.6% of the variations for protection motivation, passive and active behavior
      respectively. Protection motivation was responsible for 3.6% of passive and 8% of
      active behaviors" variations. CONCLUSION: Considering the scarceness of CED
      behaviors and the applicability of PMT in predicting these behaviors, utilization
      of the PMT"s constructs in any interventional programs to accelerate CED
      behaviors could be an alternate methodological choice in the cancer control
      initiatives.

PMID- 26290830
TI  - Risk Factors for Low Bone Mineral Density in Institutionalized Individuals with
      Developmental Disabilities.
AB  - BACKGROUND: Persons with intellectual/developmental disabilities (IDD) are
      exposed to several factors, which have been determined as risks for osteoporosis.
      Many of these individuals are non-ambulatory, resulting in lack of weight bearing
      activity, which is well established as a major contributor to bone loss. The
      purpose of this study was to investigate risk factors for low bone mineral
      density (BMD) in persons with IDD residing in residential facilities. METHODS:
      This cross-sectional study was conducted at an Intermediate Care Facility for
      individuals with Intellectual and Developmental Disabilities (ICF/IDD). Medical
      records data were used from 69 individuals, including heal scan T-scores,
      nutritional, pharmacologic and other risk factors. Chi-Square analysis was used
      to determine relationships between the variables. RESULTS: BMD measures were not
      significantly associated with age, gender, height, weight, or BMI for this
      population (P > 0.05). The association between BMD diagnoses and DSM-IV
      classification of mental retardation approached significance (P = 0.063). A
      significant association was found with anti-seizure medication (P = 0.009).
      CONCLUSION: Follow-up studies should focus on how supplementation and medication
      changes may or may not alter BMD. Persons with IDD are experiencing longer life
      expectancies, and therefore, studies ascertaining information on diseases
      associated with this aging population are warranted.

PMID- 26290831
TI  - Population-Level Equity May Not Be Achievable At the First Level of the Iranian
      Family Physician Program (IFPP).

PMID- 26290832
TI  - Aging, Fitness, and Marathon Times in a 91 Year-old Man Who Competed in 627
      Marathons.
AB  - Aging is associated with a decline in maximal aerobic capacity (VO2max) that may
      be attenuated by chronic endurance exercise. This case study chronicles the
      changes in marathon times in a 91 year old man who completed 627 marathons and
      117 ultramarathons over 42 years. He began running marathons at age 48. His
      yearly best times remained fairly constant at ~240 minutes from age 50 - 64 years
      and then gradually rose to about 260 minutes in his early seventies followed by a
      curvilinear deterioration as he approached his ninth decade. His times plateaued
      at ~ 600 minutes in his late eighties. Between ages 68 and 89 his VO2max declined
      from 43 to 20 ml/kg/min. His marathon times were highly correlated with his
      VO2max (r2=0.87). The decline in marathons times and VO2max may reflect the
      contributions of biological aging, changes in exercise training volume and
      intensity, injuries, and comorbid disease.

PMID- 26290833
TI  - Surgery of the Trachea.
AB  - Surgical procedures on the trachea have only been undertaken within the past 50
      years. Knowing the unique blood supply of the trachea and how to reduce tension
      on any anastomosis are key to a successful outcome. Tracheal conditions requiring
      surgery usually present with shortness of breath on exertion, and preoperative
      evaluation involves computed tomography and rigid bronchoscopy. Tracheal
      resection and reconstruction can be safely performed with excellent outcomes by
      following a well-described technique. 

PMID- 26290834
TI  - Change of Proximal Descending Aortic False Lumen after Conventional Repair of
      Acute Type I Dissection: Is It Always Unfavorable?
AB  - BACKGROUND: Some patients show favorable changes in the descending aortic false
      lumen after conventional repair of acute type A dissection, although the
      incidence of favorable changes has been reported to be low. We aimed to
      investigate the incidence of positive postoperative changes in the false lumen
      and the factors associated with positive outcomes. METHODS: In 63 patients who
      underwent surgery for type A acute dissection as well as serial computed
      tomography (CT) scanning, morphological parameters were compared between the
      preoperative, early postoperative (mean interval, 5.4 days), and late CT scans
      (mean interval, 31.0 months) at three levels of the descending thoracic aorta.
      RESULTS: In the early postoperative CT images, complete false lumen thrombosis
      and/or true lumen expansion at the proximal descending aorta was observed in 46%
      of the patients. In the late images, complete thrombosis or resolution of the
      proximal descending false lumen occurred in 42.9% of the patients. Multivariate
      analysis found that juxta-anastomotic false lumen thrombosis was predictive of
      favorable early changes, which were in turn predictive of continuing later
      improvement. CONCLUSION: Even after conventional repair without inserting a
      frozen elephant trunk, the proximal descending aortic false lumen showed positive
      remodeling in a substantial number of patients. We believe that the long-term
      prognosis of type A dissection can be improved by refining surgical technique,
      and particularly by avoiding large intimal tears at the anastomosis site during
      the initial repair.

PMID- 26290835
TI  - Upper Limb Ischemia: Clinical Experiences of Acute and Chronic Upper Limb
      Ischemia in a Single Center.
AB  - BACKGROUND: Upper limb ischemia is less common than lower limb ischemia, and
      relatively few cases have been reported. This paper reviews the epidemiology,
      etiology, and clinical characteristics of upper limb ischemia and analyzes the
      factors affecting functional sequelae after treatment. METHODS: The records of 35
      patients with acute and chronic upper limb ischemia who underwent treatment from
      January 2007 to December 2012 were retrospectively reviewed. RESULTS: The median
      age was 55.03 years, and the number of male patients was 24 (68.6%). The most
      common etiology was embolism of cardiac origin, followed by thrombosis with
      secondary trauma, and the brachial artery was the most common location for a
      lesion causing obstruction. Computed tomography angiography was the first-line
      diagnostic tool in our center. Twenty-eight operations were performed, and
      conservative therapy was implemented in seven cases. Five deaths (14.3%) occurred
      during follow-up. Twenty patients (57.1%) complained of functional sequelae after
      treatment. Functional sequelae were found to be more likely in patients with a
      longer duration of symptoms (odds ratio, 1.251; p=0.046) and higher lactate
      dehydrogenase (LDH) levels (odds ratio, 1.001; p=0.031). CONCLUSION: An increased
      duration of symptoms and higher initial serum LDH levels were associated with the
      more frequent occurrence of functional sequelae. The prognosis of upper limb
      ischemia is associated with prompt and proper treatment and can also be predicted
      by initial serum LDH levels.

PMID- 26290836
TI  - Pneumonectomy for Clinical Stage I Non-Small Cell Lung Cancer in Elderly Patients
      over 70 Years of Age.
AB  - BACKGROUND: Lobectomy is the generally accepted standard treatment for early
      stage non-small cell lung cancer (NSCLC). However, especially in elderly
      patients, it is often necessary to perform pneumonectomy in order to maximize the
      likelihood of curative treatment, although pneumonectomy is a challenging
      procedure. METHODS: We analysed patients who were clinically diagnosed with stage
      I NSCLC and underwent pneumonectomy with curative intent from 2004 to 2011. The
      patients were divided into an elderly group (>=70 years) and a younger group (<70
      years). We retrospectively analysed the outcomes of these groups of patients in
      order to characterize the role of pneumonectomy as a treatment for elderly
      patients with clinical stage I NSCLC. RESULTS: Thirty patients younger than 70
      years of age (younger group) and fourteen patients 70 years of age or older
      (elderly group) who underwent pneumonectomy were enrolled in the present study.
      The median follow-up period was 35 months (range, 0 to 125 months). The
      perioperative mortality rate (within 90 days after the operation) was 7.1% in the
      elderly group and 6.7% in the younger group (p=0.73). No significant differences
      between the two groups were observed regarding the occurrence of pneumonia, acute
      respiratory distress syndrome, cardiac arrhythmia, bronchopleural fistula, and
      vocal cord paralysis. The overall five-year survival rate was 79.4% in the
      younger group and 35.7% in the elderly group, which was a significant difference
      (p=0.018). The five-year disease-free survival rate was 66.7% in the younger
      group and 35.7% in the elderly group, but this difference was not statistically
      significant (p=0.23). CONCLUSION: Although elderly patients with early stage lung
      cancer showed a worse long-term survival rate after pneumonectomy than younger
      patients, the outcomes of elderly patients were similar to those of younger
      patients in terms of perioperative mortality and postoperative complications.
      Patients should not be denied pneumonectomy solely due to old age.

PMID- 26290837
TI  - Therapeutic Outcomes of Pectoralis Major Muscle Turnover Flap in Mediastinitis.
AB  - BACKGROUND: This study aimed to evaluate the therapeutic results and safety of
      pectoralis major muscle turnover flaps in the treatment of mediastinitis after
      coronary artery bypass grafting (CABG) procedures. METHODS: Data regarding 33
      patients with post-CABG deep sternal wound infections (DSWIs) who underwent
      pectoralis major muscle turnover flap procedures in the Emam Reza and Ghaem
      Hospitals of Mashhad, Iran were reviewed in this study. For each patient, age,
      sex, hospital stay duration, remission, recurrence, and associated morbidity and
      mortality were evaluated. RESULTS: Of the 2,447 CABG procedures that were carried
      out during the time period encompassed by our study, DSWIs occurred in 61
      patients (2.5%). Of these 61 patients, 33 patients (nine females [27.3%] and 24
      males [72.7%]) with an average age of 63+/-4.54 years underwent pectoralis major
      muscle turnover flap placement. Symptoms of infection mainly occurred within the
      first 10 days after surgery (mean, 10.24+/-13.62 days). The most common risk
      factor for DSWIs was obesity (n=16, 48.4%) followed by diabetes mellitus (n=13,
      39.4%). Bilateral and unilateral pectoralis major muscle turnover flaps were
      performed in 20 patients (60.6%) and 13 patients (39.4%), respectively. Complete
      remission was achieved in 25 patients (75.7%), with no recurrence in the follow
      up period. Four patients (12.1%) needed reoperation. The mean hospitalization
      time was 11.69+/-6.516 days. Four patients (12.1%) died during the course of the
      study: three due to the postoperative complication of respiratory failure and one
      due to pulmonary thromboembolism. CONCLUSION: Pectoralis major muscle turnover
      flaps are an optimal technique in the treatment of post-CABG mediastinitis. In
      addition to leading to favorable therapeutic results, this flap is associated
      with minimal morbidity and mortality, as well as a short hospitalization time.

PMID- 26290838
TI  - Multifilament Cable Wire versus Conventional Wire for Sternal Closure in Patients
      Undergoing Major Cardiac Surgery.
AB  - BACKGROUND: Stainless steel wiring remains the most popular technique for primary
      sternal closure. Recently, a multifilament cable wiring system (Pioneer Surgical
      Technology Inc., Marquette, MI, USA) was introduced for sternal closure and has
      gained wide acceptance due to its superior resistance to tension. We aimed to
      compare conventional steel wiring to multifilament cable fixation for sternal
      closure in patients undergoing major cardiac surgery. METHODS: Data were
      collected retrospectively on 1,354 patients who underwent sternal closure after
      major cardiac surgery, using either the multifilament cable wiring system or
      conventional steel wires between January 2009 and October 2010. The surgical
      outcomes of these two groups of patients were compared using propensity score
      matching based on 18 baseline patient characteristics. RESULTS: Propensity score
      matching yielded 392 pairs of patients in the two groups whose baseline profiles
      showed no significant differences. No significant differences between the two
      groups were observed in the rates of early mortality (2.0% vs. 1.3%, p=0.578),
      major wound complications requiring reconstruction (1.3% vs. 1.3%, p>0.99), minor
      wound complications (3.6% vs. 2.0%, p=0.279), or mediastinitis (0.8% vs. 1.0%,
      p=1.00). Patients in the multifilament cable group had fewer sternal bleeding
      events than those in the conventional wire group, but this tendency was not
      statistically significant (4.3% vs. 7.4%, p=0.068). CONCLUSION: The surgical
      outcomes of sternal closure using multifilament cable wires were comparable to
      those observed when conventional steel wires were used. Therefore, the
      multifilament cable wiring system may be considered a viable option for sternal
      closure in patients undergoing major cardiac surgery.

PMID- 26290839
TI  - Valve Sparing Aortic Root Replacement in Children with Loeys-Dietz Syndrome.
AB  - Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder
      that is characterized by aggressive arterial and aortic disease, often involving
      the formation of aortic aneurysms. We describe the cases of two children with LDS
      who were diagnosed with aortic root aneurysms and successfully treated by valve
      sparing aortic root replacement (VSRR) with a Valsalva graft. VSRR is a safe and
      suitable operation for children that avoids prosthetic valve replacement. 

PMID- 26290840
TI  - Heart Transplantation in a Patient with Left Isomerism.
AB  - We report the case of a 37-year-old man who suffered from biventricular failure
      due to left isomerism, inferior vena cava interruption with azygos vein
      continuation, bilateral superior vena cava, double outlet of right ventricle,
      complete atrioventricular septal defect, pulmonary stenosis, and isolated
      dextrocardia. Heart transplantation in patients with systemic venous anomalies
      often requires the correction and reconstruction of the upper & lower venous
      drainage. We present a case of heart transplantation in a patient with left
      isomerism, highlighting technical modifications to the procedure, including the
      unifocalization of the caval veins and reconstruction with patch augmentation. 

PMID- 26290841
TI  - Traumatic Coronary Artery Dissection in a Young Woman after a Kick to Her Back.
AB  - We present the case of a 38-year-old woman admitted to our outpatient clinic with
      accelerating back pain and fatigue following a kick to her back by her husband.
      Upon arrival, we detected ST segment elevation in the D1, aVL, and V2 leads and
      accelerated idioventricular rhythm. She had pallor and hypotension consistent
      with cardiogenic shock. We immediately performed coronary angiography and found a
      long dissection starting from the mid-left main coronary artery and progressing
      into the mid-left anterior descending (LAD) and circumflex arteries. She was then
      transferred to the operating room for surgery. A saphenous vein was grafted to
      the distal LAD. Since the patient was hypotensive under noradrenaline and
      dopamine infusions, she was transferred to the cardiovascular surgery intensive
      care unit on an extracorporeal membrane oxygenator and intra-aortic balloon pump.
      During follow-up, her blood pressure remained low, at approximately 60/40 mmHg,
      despite aggressive inotropic and mechanical support. On the second postoperative
      day, asystole and cardiovascular arrest quickly developed, and despite aggressive
      cardiopulmonary resuscitation, she died. 

PMID- 26290842
TI  - Long Segmental Reconstruction of Diffusely Diseased Left Anterior Descending
      Coronary Artery Using Left Internal Thoracic Artery with Extensive
      Endarterectomy.
AB  - In coronary artery bypass grafting, a diffusely diseased left anterior descending
      coronary artery (LAD) is an obstacle to achieving complete revascularization,
      consequently leading to the possibility of a poor prognosis. Long segmental
      reconstruction with or without endarterectomy is a revascularization method for
      treating diffusely diseased coronary arteries. Herein, we report a successful
      case of long segmental reconstruction of a diffusely diseased LAD using a left
      internal thoracic artery onlay patch after endarterectomy. 

PMID- 26290844
TI  - Epithelioid Hemangioendothelioma Arising from Interanl Jugular Vein Mimicking
      Cervical Metastatic Lymphadenopathy.
AB  - Epithelioid hemangioendothelioma (EHE) is a relatively rare and moderately
      aggressive type of vascular tumor. We describe a case of EHE that presented in a
      24-year-old woman as a palpable nodule in the left cervical area. Radiological
      examinations and fine-needle aspiration cytology led to a preliminary diagnosis
      of metastatic lymphadenopathy with an unknown primary site. However, during
      surgery, we determined that the nodule was an intra-vascular tumor arising from
      the left internal jugular vein. The histopathological examination revealed cords
      of epithelioid endothelial cells distributed in a hyaline stroma, compatible with
      a diagnosis of EHE. 

PMID- 26290843
TI  - Right Heart Failure during Veno-Venous Extracorporeal Membrane Oxygenation for
      H1N1 Induced Acute Respiratory Distress Syndrome: Case Report and Literature
      Review.
AB  - A 38-year-old male was admitted with symptoms of upper respiratory infection.
      Despite medical treatment, his symptoms of dyspnea and anxiety became aggravated,
      and bilateral lung infiltration was noted on radiological imaging studies. His
      hypoxemia failed to improve even after the application of endotracheal intubation
      with mechanical ventilator care, and we therefore decided to initiate venovenous
      extracorporeal membrane oxygenation (VV ECMO) for additional pulmonary support.
      On his twentieth day of hospitalization, hypotension and desaturation (arterial
      saturated oxygen <85%) developed, and right ventricular failure was confirmed by
      two-dimensional echocardiography. Therefore, we changed from VV ECMO to
      venoarteriovenous (VAV) ECMO, and the patient ultimately recovered. In this case,
      right ventricular dysfunction and volume overloading were induced by long-term VV
      ECMO therapy, and we successfully treated these conditions by changing to VAV
      ECMO. 

PMID- 26290845
TI  - Bronchial Artery Aneurysm Presenting as Hematemesis and Mediastinal Hemorrhage.
AB  - Hematemesis is a rare manifestation of a ruptured bronchial artery aneurysm (BAA)
      in the mediastinum. It is difficult to diagnose a ruptured BAA presenting as
      hematemesis, because it can be confused with other diseases, such as Boerhaave's
      syndrome, variceal disease, or a perforated ulcer. In this report, we describe a
      case of BAA resulting in hematemesis and mediastinal hemorrhage. 

PMID- 26290846
TI  - Pseudoaneurysm with Arteriovenous Fistula after Arthroscopic Procedure: A Rare
      Complication of Arthroscopy.
AB  - Pseudoaneurysm with arteriovenous fistula is a rare complication of arthroscopy,
      and can be diagnosed by ultrasonography, computed tomography, magnetic resonance
      imaging, or angiography. This condition can be treated with open surgical repair
      or endovascular repair. We report our experience with the open surgical repair of
      a pseudoaneurysm with an arteriovenous fistula in a young male patient who
      underwent arthroscopy five months previously. 

PMID- 26290847
TI  - Unusual Presentation of Renal Cell Carcinoma in Crossed Ectopic Kidney.
AB  - INTRODUCTION: Crossed renal ectopia is a rare anomaly and ninety percent of
      crossed ectopic kidneys are fused to their ipsilateral mate. Based on autopsy
      findings, the incidence has been estimated to be one in 2000 individuals. CASE
      PRESENTATION: We hereby report on a 53-year-old woman with two episodes of
      painless gross hematuria. Imaging revealed left side fused crossed renal ectopia
      and filling defect within the pyelocaliceal of crossed kidney. CONCLUSIONS: The
      patient underwent surgery applying a midline incision. The left kidney showed a
      lump pattern embedded in lower pole of the right kidney. Left sided nephrectomy
      was performed while temporary right renal artery was clamped temporarily.
      Histopathological evaluation revealed clear cell carcinoma with severe nuclear
      atypia (Fuhrman grade 4/4). However, local recurrence was not detected during the
      18-month follow up after surgery.

PMID- 26290848
TI  - Comparison of the Efficacy of Two Brands of Triptorelin (Microrelin and
      Diphereline) in Reducing Prostate-Specific Antigen and Serum Testosterone in
      Prostate Cancer: A Double-Blinded Randomized Clinical Trial.
AB  - BACKGROUND: Gonadotropin-releasing hormone (GnRH) agonists initiate androgen
      deprivation in treating prostate cancer (PC). Triptorelin is a synthetic GnRH and
      many of its market brands such as Diphereline have been introduced so far.
      OBJECTIVES: We compared the efficacy of a sustained-release formulation of
      Triptorelin (Microrelin), domestically produced in Iran, and compared it with
      Diphereline in a double-blinded randomized clinical trial. PATIENTS AND METHODS:
      Patients were randomly assigned to Group A (Microrelin S.R. 3.75 mg, Pooyesh
      Darou, Iran) and Group B (Diphereline S.R. 3.75 mg, IPSEN, France). Each patient
      received monthly intramuscular injections. Prostate-specific antigen (PSA) and
      circulatory testosterone were measured at baseline and after one, 3, and 6
      months. RESULTS: Each group contained 40 patients. In Group A, PSA was reduced
      from 75.78 +/- 72.43 ng/mL to 1.93 +/- 1.40 ng/mL after 6 months and testosterone
      was reduced from 3.50 +/- 1.12 nmol/L to 0.81 +/- 0.05 nmol/L. There was no
      significant difference between the efficacy of Microrelin and Diphereline. Two
      patients in the Microrelin Group and one patient in the Diphereline Group failed
      to reach medical castration (testosterone < 1.7 nmol/L), which illustrates that
      the power of Microrelin and Dipherelin in initiating medical castration is about
      95% and 97.5%, respectively. CONCLUSIONS: Our study showed that Microrelin is as
      effective as Diphereline in reducing PSA and testosterone and can be recommended
      to initiate medical castration in patients with PC.

PMID- 26290849
TI  - Associations Between Hyperuricemia and Chronic Kidney Disease: A Review.
AB  - CONTEXT: In human beings, uric acid is the poorly soluble circulating end product
      of the purine nucleotide metabolism. A reduction in the glomerular filtration
      rate (GFR) contributes to hyperuricemia, which is frequently observed in patients
      with chronic kidney disease (CKD). EVIDENCE ACQUISITION: Hyperuricemia is defined
      as a serum uric acid level > 7.0 mg/dL in males and > 6.0 mg/dL in females, while
      CKD is defined as kidney damage or a GFR < 60 mL/min/1.73 m(2) for 3 months or
      more, irrespective of the cause. Hyperuricemia is common in CKD and may occur
      because of decreased excretion, increased production, or a combination of both
      mechanisms. RESULTS: The causes for hyperuricemia in overproducers may be either
      exogenous or endogenous. CKD has become a global public health problem because of
      its high prevalence and the accompanying increase in the risk of end-stage renal
      disease, cardiovascular disease, and premature death. The most common risk
      factors for CKD are obesity and the metabolic syndrome, which is strongly
      associated with hyperuricemia probably as a consequence of insulin resistance and
      the effects of insulin to reduce the urinary urate excretion. For recurring bouts
      of hyperuricemia or gout, patients should have a blood test and joint fluid test
      to determine whether the medication taken is effective. Interventional studies
      are a useful clinical research tool in clarifying the role of hyperuricemia in
      CKD. CONCLUSIONS: Although many evidence-based studies have suggested that uric
      acid itself may harm patients with CKD by increasing inflammation and CKD
      progression, the issue is still a matter of controversy. Special attention should
      be paid to specific contraindications to certain drugs and the possibility of
      infectious arthritis.

PMID- 26290850
TI  - Does Metabolic Syndrome or its Components Correlate With Lower Urinary Tract
      Symptoms in Benign Prostatic Hyperplasia Patients?
AB  - BACKGROUND: Metabolic Syndrome (MS) has become a global public health and has
      been suggested to be a risk factor for Lower Urinary Tract Symptoms (LUTS).
      Studies evaluating the association between the rate of the MS and LUTS often
      showed controversial results. OBJECTIVES: The purpose of this study was to reveal
      the relevance of MS and its components on the frequency and severity of the LUTS
      that were seen with Benign Prostate Hyperplasia (BPH) in Turkish men or not.
      PATIENTS AND METHODS: In this study, 237 patients referred to urology policlinic
      with BPH were retrospectively scanned between April 2009 and April 2013. Patients
      with normal digital rectal examination and the Prostate Specific Antigen (PSA)
      level of <= 4 ng/mL were evaluated using the International Prostate Symptom Score
      (IPSS) and all the data of the patients' body, including Body Mass Index (BMI),
      lipid parameters, preprandial blood glucose, and waist circumference. Seventy
      four patients (31.3%) with mild IPSS (0-7) was group 1; 97 patients (40.9%) with
      moderate IPSS (8 - 19) group 2 and 66 patients (27.8%) with severe IPSS (20-35)
      were defined as group 3. group 4 consisted of 117 healthy controls. Three groups
      and controls were compared about MS and its components. The diagnosis criteria of
      The Society of Endocrinology and Metabolism of Turkey were used in MS diagnosis.
      Also, BMI, lipid parameters, preprandial blood glucose, waist circumference, and
      blood pressure were used as MS parameters. RESULTS: The average age of patients
      in group 1 was 69.8 +/- 7.2; in group 2, 69.1 +/- 7.4; 68.3 +/- 7.1 in group 3
      and 70.2 +/- 7.2 in the control group. Metabolic syndrome was determined at 37
      patients (50%) in group 1, 45 patients (46.5%) in group 2, 32 patients (48%) in
      group 3 and 52 patients (44.4%) in controls and no statistically significant
      correlation was detected between LUTS and MS in BPH (P = 0.113). In the
      comparison of the four groups in the point of MS parameters, no significant
      correlation was detected in the levels of total cholesterol (P = 0.337), fasting
      glucose (P = 0.291), BMI (P = 0.452), Low Density Lipoprotein (LDL, P = 0.069)
      and triglyceride (P = 0.307). CONCLUSIONS: In our study, the evidence is not
      enough to support the hypothesis of the relevance between MS and LUTS. Wide
      ranging, prospective and multicentric studies are needed to research the
      relevance between MS and LUTS in BPH.

PMID- 26290851
TI  - Propofol Versus Midazolam for Procedural Sedation of Anterior Shoulder
      Dislocation in Emergency Department: A Randomized Clinical Trial.
AB  - BACKGROUND: Anterior shoulder dislocation (ASD) is one of the most common reasons
      for referrals to emergency departments (ED). Usually, a combination of an
      intravenous narcotic and a benzodiazepine is used for procedural sedation and
      analgesia (PSA) in such cases. OBJECTIVES: This study compares the efficacy of
      two combinations to reduce ASD. PATIENTS AND METHODS: The subjects in this
      clinical trial consisted of 48 patients with ASD who were randomly assigned to
      midazolam/fentanyl and propofol/fentanyl groups for PSA. The two groups were
      compared to the time interval between injection and induction of sedation (T1),
      duration of time from sedation to awakening (T2), the duration of time between
      sedation and full awareness to time, location and individuals (T3), and possible
      side effects. RESULTS: Twenty-nine subjects (60.4%) were sedated with midazolam
      and 19 (39.6%) were sedated with propofol. During the procedure, one patient in
      the propofol group experienced apnea (P = 0.39) and three patients (one in the
      midazolam group and two in the propofol group) experienced bradycardia (P =
      0.34). The mean T1, T2, and T3 were significantly shorter in the propofol group
      (P < 0.001). CONCLUSIONS: It seems that propofol and fentanyl can be used as a
      safe and fast combination for PSA in the reduction of ASD.

PMID- 26290852
TI  - Association of Soccer and Genu Varum in Adolescents.
AB  - BACKGROUND: Genu varum is a physical deformity marked by bowing of the leg. One
      of the risk factors of this musculoskeletal alignment is stress on the knee joint
      such as with exercise. OBJECTIVES: Since the evaluation of genu varum has not
      been widely studies, this study was conducted to examine the association between
      genu varum and playing soccer. MATERIALS AND METHODS: Between Septembers 2010
      2012, 750 soccer players and 750 non-soccer players 10-18 years of age were
      included in the study. A questionnaire of data including age, height, weight,
      body mass index (BMI), years of soccer participation, the average time of playing
      soccer per week, previous trauma to the lower limbs, history of any fractures of
      the knee, previous hospitalizations, and the distance of joint lines between the
      knees was assessed for all subjects. Chi-square, student t-test, and one-way
      ANOVA were used for statistical analysis by SPSS v.19.0 software. In all tests, a
      P value of less than 0.05 was construed as statistically significant. RESULTS:
      Both soccer players and controls had genu varum. However, the incidence of genu
      varum was higher in the soccer players (P = 0.0001) and it was more prevalent in
      the 16-18 year age group (P = 0.0001). The results revealed a statistically
      significant association between the degree of practices and the prevalence of
      genu varum (P = 0.0001). Moreover, previous trauma to the knees and practicing in
      load-bearing sports led to an increase in the degree of genu varum (P = 0.0001).
      CONCLUSIONS: There was a higher incidence of genu varum in soccer players than in
      control adolescents; the stress and load imposed on the knee joint led to more
      severe genu varum.

PMID- 26290853
TI  - Effect of Education on Stress of Exposure to Sharps Among Nurses in Emergency and
      Trauma Care Wards.
AB  - BACKGROUND: Health care services can cause injuries to medical staff. One of
      these injuries is exposure to needle-sticks. This can result in the transmission
      of blood-borne diseases, such as HIV and hepatitis B; the staff undergo
      continuous stress. Thus, it is necessary to use some method to reduce this
      stress. OBJECTIVES: The purpose of this study was to examine the effect of
      education based on the stabilization model on stress induced exposure to needle
      sticks among nurses working in emergency and trauma wards. PATIENTS AND METHODS:
      This Quast- Experiental Study was performed on 35 nurses working in emergency and
      trauma wards of our hospital in October-December 2013. Data were collected using
      a two-part questionnaire; Reliability and validity of the questionnaire were
      confirmed (alpha = 0. 92 and ICC = 0.94).Data were analyzed using SPSS version
      20. The one-sample Kolmogorov-Smirnov test, independent t-test and paired sample
      t-test were also used. RESULTS: The mean and standard deviation of stress
      experienced by nurses before and after the intervention were 64.94 +/- 15.67 and
      43.91 +/- 10.73, respectively. Findings indicated that education decrease needle
      stick stress in nurses significantly (P < 0.001). CONCLUSIONS: According to the
      results of this study, the stress level induced due to needle-stick exposure and
      its complications is high and interventions for reduction are essential.

PMID- 26290854
TI  - Delirium in Prolonged Hospitalized Patients in the Intensive Care Unit.
AB  - BACKGROUND: Prolonged hospitalization in the intensive care unit (ICU) can impose
      long-term psychological effects on patients. One of the most significant
      psychological effects from prolonged hospitalization is delirium. OBJECTIVES: The
      aim of this study was to assess the effect of prolonged hospitalization of
      patients and subsequent delirium in the intensive care unit. PATIENTS AND
      METHODS: This conventional content analysis study was conducted in the General
      Intensive Care Unit of the Shariati Hospital of Tehran University of Medical
      Sciences, from the beginning of 2013 to 2014. All prolonged hospitalized patients
      and their families were eligible participants. From the 34 eligible patients and
      63 family members, the final numbers of actual patients and family members were 9
      and 16, respectively. Several semi-structured interviews were conducted face-to
      face with patients and their families in a private room and data were gathered.
      RESULTS: Two main themes from two different perspectives emerged, 'patients'
      perspectives' (experiences during ICU hospitalization) and 'family members'
      perspectives' (supportive-communicational experiences). The main results of this
      study focused on delirium, Patients' findings were described as pleasant and
      unpleasant, factual and delusional experiences. CONCLUSIONS: Family members are
      valuable components in the therapeutic process of delirium. Effective use of
      family members in the delirium caring process can be considered to be one of the
      key non-medical nursing components in the therapeutic process.

PMID- 26290855
TI  - Analgesic Effect of Clonidine Added to Bupivacaine in Spinal Anesthesia for
      Cruciate Ligament Repair.
AB  - BACKGROUND: Several researchers have suggested that addition of local anesthetics
      to spinal anesthesia increases the duration of post-operative analgesia.
      OBJECTIVES: This study sought to assess the effect of addition of clonidine to
      bupivacaine in spinal anesthesia on analgesia after cruciate ligament repair.
      PATIENTS AND METHODS: This double-blind clinical trial was conducted on 50
      American Society of Anesthesiologists (ASA) class I or II patients who were
      candidates for cruciate ligament repair. Patients were randomly assigned to two
      groups; one group received 15 mg of bupivacaine (group B) and the other 15 mg of
      bupivacaine plus clonidine (75 ug, group BC). The two groups were compared in
      terms of post-operative analgesia and related factors using the SPSS software
      version 20. RESULTS: All patients were males with a mean age of 24.9 years in
      group B, and 25.2 years in group BC (P > 0.05). In group BC, time lapse to
      request analgesics was 160 minutes longer and the Visual Analog Scale (VAS) at
      this time was 0.3 units less than group B. The time to regression of sensory
      block by two dermatomes was seven minutes longer, VAS in the recovery room was 1
      unit less and Bromage scale in the recovery room and ward was 0.6 and 0.9 units
      more, respectively in the BC group. Hypotension and ephedrine usage was 36% more
      in the BC group (P < 0.05). CONCLUSIONS: Clonidine plus bupivacaine can increase
      the duration of motor and sensory block in arthroscopic cruciate ligament repair
      under spinal anesthesia. However, due to significant hemodynamic changes, further
      studies are required to determine a safer dose.

PMID- 26290856
TI  - Outcomes of Traumatic Aortic Injury in a Primary Open Surgical Approach Paradigm.
AB  - BACKGROUND: Multiple classifications can be used to define the magnitude of
      aortic injury. The Vancouver Classification (VC) is a new and simplified computed
      tomography-based Blunt Aortic Injury (BAI) grading system correlating with
      clinical outcomes. OBJECTIVES: The objectives of this study are: 1) to describe
      the severity of aortic injury in a center with a predominantly surgical approach
      to BAI; 2) to correlate the severity of aortic trauma to hospital survival rate
      and rate of adverse events according to the type of interventions performed
      during the hospital stay; and 3) to evaluate VC. PATIENTS AND METHODS: All
      patients referring to the Sacre-Coeur Hospital of Montreal between August 1998
      and April 2011 for management of BAI were studied. Two radiologists reviewed all
      CT scan images individually and classified the aortic injuries using VC. RESULTS:
      Among the 112 patients presenting with BAI, 39 cases had local CT scans available
      for reconstruction. Seven patients were identified as suffering from grade I
      injuries (flap or thrombus of less than 1 cm), 6 from grade II injuries (flap or
      thrombus of more than 1 cm), and 26 from grade III injuries (pseudoaneurysm).
      Among the patients with grade I injuries, 57% were treated surgically and 43%
      medically with a survival rate of 100%. Among the patients with grade II injuries
      (67% treated surgically and 33% treated medically) survival was also 100%. Among
      patients with grade III injuries (85% treated surgically, 7% had Thoracic
      Endovascular Aortic Repair (TEVAR) and 8% treated medically) survival was 95%,
      95% and 50%, respectively. There were no significant differences between groups
      as to clinical outcome. Inter-rater reliability was 0.81. CONCLUSIONS: VC is easy
      to use and has low inter-observer variability. Low grades of injury were
      associated with low mortality related to medical treatment.

PMID- 26290857
TI  - Relationship Between Low Back Pain With Quality of Life, Depression, Anxiety and
      Stress Among Emergency Medical Technicians.
AB  - BACKGROUND: Musculoskeletal disorders have become increasingly common among
      healthcare providers. They have become the most common cause of work-related
      disabilities among nurses. OBJECTIVES: The current cross-sectional study aimed to
      measure the prevalence of back pains among emergency medical technicians (EMTs),
      and association of back pain with quality of life, depression, anxiety and
      stress. MATERIALS AND METHODS: One hundred and eighty registered nurses working
      as EMTs at the Hamadan Emergency Medical Center were selected by consensus. Data
      collection tools were Demographic, Perceived Quality-of-Life, Short Form Health
      Survey (SF-36), and Depression Anxiety Stress Scales (DAS21) and pain scale
      measurements. RESULTS: Data showed that while 50.7% of the participants had an
      average awareness of the basic principles of back care, the majority (71.8%) had
      at least one type of back pain. There were associations between the prevalence of
      pain and depression (P = 0.049), pain and awareness (P = 0.035), and stress and
      job satisfaction (P = 0.024). CONCLUSIONS: A large number (about two-thirds) of
      EMTs had some sort of back pain; it is highly recommended to promote the attitude
      and motivation of the individuals to take care to prevent back injury and inform
      them of the principles of back care. Implications for primary prevention and care
      practice include encouraging EMTs to apply accurate principles of back care.

PMID- 26290858
TI  - Laser Therapy After Repair of the Distal Half of the Median Nerve; a Comparative
      Study.
AB  - BACKGROUND: Nerve injuries resulting from major or minor trauma often cause some
      disabilities for patients. Neurotmesis, characterized by complete anatomical
      rupture of the nerve, is the most severe form of the injury which will not
      recover without reconstructive surgery and nowadays such neural damages are
      improved by microsurgical procedures. Some studies have used low power laser for
      nerve cell growth in order to improve the rehabilitation results of peripheral
      nerves. Low power laser can complement the reformation of postsurgical nerve
      injuries. OBJECTIVES: The current study aimed to assess the effects of laser
      therapy after repair of median nerve rupture in the distal third of the forearm
      and to compare the results with that of the standard method. PATIENTS AND
      METHODS: The current study was a case-control clinical trial of 36 patients with
      volar surface rupture of the distal third of forearm admitted to the emergency
      ward of Hazrat-e-Fatemeh Hospital within 72 hours of injury, they had anesthesia
      in the first, second, and third fingers as a result of Median Nerve Injury.
      Patients were divided into two groups. The first group included subjects treated
      with standard methods and the second group included those treated with low power
      laser therapy (LT) along with the standard method. The same surgeon operated the
      subjects in the two groups. The second group underwent 10 sessions of LT every
      other day. Clinical Examination, Electromyography and Nerve Conduction Velocity
      (NCV) were done after six months and the results were compared. RESULTS: In the
      two -point discrimination- test, there was no significant difference between the
      two groups in the thumbs but a significant improvement was observed in the index
      finger of the LT group. Improvement of muscular examinations such as opposition
      and thumb abduction supported the usage of laser in the second group. Regarding
      electromyography and NCV, significant statistical difference was observed in the
      motor part of the laser group and, to a great extent, was compatible with the
      physical examinations. CONCLUSIONS: Accordingly, laser therapy in our protocol
      seemed to affect some of the nerve growth parameters, mostly on motor rather than
      sensory fibers.

PMID- 26290859
TI  - Relationship of Moral Sensitivity and Distress Among Physicians.
AB  - BACKGROUND: Providing health services is described as an important moral measure,
      since its major aim is to ensure the welfare of the people who need treatment and
      care. Moral sensitivity is the ability to identify the existing moral problem and
      understand the moral consequences of the decisions made on the patient's part.
      Physicians are always exposed to moral distress due to various circumstances.
      OBJECTIVES: In this survey, we evaluated moral sensitivity and moral distress
      among physicians and the relationship of these ethical factors on them. Hence, we
      assessed y relationship between moral sensitivity and moral distress in
      physicians will facilitate their sound management so as to provide high-quality
      and safe health services. Moreover it will confirm proposed theories regarding
      this subject. MATERIALS AND METHODS: This cross-sectional descriptive-analytic
      study aimed at investigating the relationship between moral sensitivity and moral
      distress among 321 specialist physicians working in hospitals affiliated to
      Tehran Medical Universities in Tehran. The samples were selected through two
      stage random cluster sampling method. A three-partite questionnaire comprising of
      demographic characteristics, moral distress, and moral sensitivity was used for
      collecting data which then were analyzed using SPSS-20. RESULTS: There was a
      negative significant relationship between moral sensitivity and moral distress
      frequency; there was a positive significant relationship between moral
      sensitivity and moral distress intensity. Participating in medical ethics courses
      increased moral sensitivity and decreased the frequency of moral distress.
      CONCLUSIONS: Participating in medical ethics courses increased moral sensitivity
      and decreased the frequency of moral distress.

PMID- 26290860
TI  - National Getaways for the Weary Trauma Surgeon; Part 3: Dizin Ski Resort.

PMID- 26290861
TI  - Production and Comprehension of Time Reference in Korean Nonfluent Aphasia.
AB  - OBJECTIVES: Individuals with nonfluent agrammatic aphasia show impaired
      production and comprehension of time reference via verbal morphology. However,
      cross-linguistic findings to date suggest inconsistent evidence as to whether
      tense processing in general is impaired or time reference to the past is
      selectively difficult in this population. This study examined production and
      comprehension of time reference via verb morphology in Korean-speaking
      individuals with nonfluent aphasia. METHODS: A group of 9 healthy controls and 8
      individuals with nonfluent aphasia (5 for the production task) participated in
      the study. Sentence priming production and auditory sentence to picture matching
      tasks were used, parallel with the previous cross-linguistic experiments in
      English, Chinese, Turkish, and others. RESULTS: The participants with nonfluent
      aphasia showed different patterns of impairment in production and comprehension.
      In production, they were impaired in all time references with errors being
      dominated by substitution of incorrect time references and other morpho
      phonologically well-formed errors, indicating a largely intact morphological
      affixation process. In comprehension, they showed selective impairment of the
      past, consistent with the cross-linguistic evidence from English, Chinese,
      Turkish, and others. CONCLUSION: The findings suggest that interpretation of past
      time reference poses particular difficulty in nonfluent aphasia irrespective of
      typological characteristics of languages; however, in production, language
      specific morpho-semantic functions of verbal morphology may play a significant
      role in selective breakdowns of time reference.

PMID- 26290862
TI  - Non-Alcoholic Steatohepatitis: Pathogenesis and Clinical Management.

PMID- 26290864
TI  - Erratum to "Localized and Sustained Delivery of Erythropoietin from PLGA
      Microspheres Promotes Functional Recovery and Nerve Regeneration in Peripheral
      Nerve Injury".

PMID- 26290863
TI  - Lower Urinary Tract Symptoms Are Associated with Increased Risk of Dementia among
      the Elderly: A Nationwide Study.
AB  - Studies show a strong association between dementia and lower urinary tract
      symptoms (LUTS). The aim of this study was to investigate whether LUTS are a risk
      factor for cognitive impairment. We enrolled 50-year-old and older subjects with
      LUTS (LUTS([+])) (n = 6801) and controls without LUTS (LUTS([-])) (n = 20,403)
      from Taiwan's National Health Insurance Research Database. LUTS, dementia, and
      other confounding factors are defined by International Classification of
      Diseases, Ninth Revision, Clinical Modification Codes. Participants were
      recruited from 2000 to 2004 and then followed up until death or the end of 2011.
      The outcome was the onset of dementia, which was assessed using Poisson
      regression analysis, Cox hazards models, and Kaplan-Meier survival curves. The
      incidence of dementia was significantly higher in the LUTS([+]) group than in the
      LUTS([-]) group (124.76 versus 77.59/1000 person-years). The increased risk of
      dementia related to LUTS remained significant after adjustment for potential
      confounders (adjusted hazard ratio (AHR): 1.61, 95% confidence interval (CI) 1.47
      1.76, P < 0.0001) and higher than that related to cerebrovascular disease (AHR:
      1.43, 95% CI 1.26-1.61, P < 0.0001). The outcome suggests the need for early
      screening and appropriate intervention to help prevent cognitive impairment of
      patients with LUTS. 

PMID- 26290865
TI  - Demodex sp. as a Potential Cause of the Abandonment of Soft Contact Lenses by
      Their Existing Users.
AB  - Demodex mites may be a potential etiological factor in the development of various
      eye and skin disorders. The aim of the study was to investigate the presence of
      Demodex in the hair follicles of eyelashes and their potential influence on
      abandoning soft contact lenses which had been previously well tolerated by their
      users. A group of 62 users of contact lenses (28 with emerging discomfort and 34
      without discomfort) were examined. There is a need to check the existence of a
      relationship between D. folliculorum or/and D. brevis infestation and the
      emergence of intolerance to the presence of soft contact lenses. The removed
      lashes were examined under light microscopy, applying standard parasitological
      methods if demodicosis is suspected. A positive result was assumed if at least
      one adult stage, larva, protonymph/nymph, or egg of D. folliculorum and/or D.
      brevis was present. A positive correlation was observed between the presence of
      Demodex and intolerance to contact lenses by their existing users (p < 0.05), and
      Demodex sp. infections were observed in 92.86% of patients with intolerance to
      contact lenses. Our results provide further evidence for the pathogenic role
      played by the mites in the development of eye diseases. 

PMID- 26290866
TI  - Transdermal Nicotine Application Attenuates Cardiac Dysfunction after Severe
      Thermal Injury.
AB  - BACKGROUND: Severe burn trauma leads to an immediate and strong inflammatory
      response inciting cardiac dysfunction that is associated with high morbidity and
      mortality. The aim of this study was to determine whether transdermal application
      of nicotine could influence the burn-induced cardiac dysfunction via its known
      immunomodulatory effects. MATERIAL AND METHODS: A standardized rat burn model was
      used in 35 male Sprague Dawley rats. The experimental animals were divided into a
      control group, a burn trauma group, a burn trauma group with additional nicotine
      treatment, and a sham group with five experimental animals per group. The latter
      two groups received nicotine administration. Using microtip catheterization,
      functional parameters of the heart were assessed 12 or 24 hours after infliction
      of burn trauma. RESULTS: Burn trauma led to significantly decreased blood
      pressure (BP) values whereas nicotine administration normalized BP. As expected,
      burn trauma also induced a significant deterioration of myocardial contractility
      and relaxation parameters. After application of nicotine these adverse effects
      were attenuated. CONCLUSION: The present study showed that transdermal nicotine
      administration has normalizing effects on burn-induced myocardial dysfunction
      parameters. Further research is warranted to gain insight in molecular mechanisms
      and pathways and to evaluate potential treatment options in humans.

PMID- 26290867
TI  - Moderate Dietary Supplementation with Omega-3 Fatty Acids Does Not Impact Plasma
      Von Willebrand Factor Profile in Mildly Hypertensive Subjects.
AB  - Long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) have blood pressure
      lowering and antithrombotic effects, which may benefit hypertensive patients.
      Increased plasma concentration of von Willebrand factor (vWF), a procoagulant
      glycoprotein, has been identified in patients with severe hypertension, with
      some, but not all studies showing an increase with mild hypertension. In this
      study, we determined the plasma concentration, multimer distribution, and
      collagen binding activity of vWF in subjects with mild hypertension and
      determined whether these parameters might improve after dietary supplementation
      with moderate amounts of LC n-3 PUFAs. Hypertensive and normotensive subjects
      were randomized to 12-week treatment with LC n-3 PUFAs (2.52 g/day) or placebo
      (canola oil). Home blood pressure measurements were recorded daily, and blood
      samples were collected every 3 weeks. LC n-3 PUFAs increased the n-3 index to
      cardioprotective levels (>8%). Plasma concentration, multimer distribution, and
      collagen binding activity of vWF were not reduced by LC n-3 PUFA treatment. We
      conclude that, at the concentration and duration used in this study, benefits of
      LC n-3 PUFAs in subjects with mild hypertension are not associated with a direct
      effect on vWF concentration or function. This trial is registered with the
      Australian New Zealand Clinical Trials Registry ACTRN12610000713099.

PMID- 26290868
TI  - Microbial Diversity for Biotechnology 2014.

PMID- 26290871
TI  - Modification of S. cerevisiae Growth Dynamics Using Low Frequency Electromagnetic
      Fields in the 1-2 kHz Range.
AB  - This paper details our further experiments pertaining to the influence of low
      frequency electromagnetic fields (LF EMF) on the growth dynamics of two wild-type
      Saccharomyces cerevisiae strands. We opted to explore frequencies beyond the
      usual 50-60 Hz range, motivated by the ion parametric resonance theory and
      several studies which discovered and recorded endogenous biosignals in various
      Saccharomyces cerevisiae strands in the 0.4-2.0 kHz frequency range, most
      probably stemming from microtubules. Both yeast strands used in our experiments
      have been subjected to continuous 66-hour session of LF EMF exposure (frequencies
      1.2, 1.4, 1.6, 1.8, and 2.0 kHz; average magnetic flux density 2.43 mT) under
      identical ambient conditions. Experiment results indicate a frequency-dependent
      proliferative response of both yeast strands.

PMID- 26290869
TI  - Increased Standardised Incidence Ratio of Malignant Pleural Mesothelioma in
      Taiwanese Asbestos Workers: A 29-Year Retrospective Cohort Study.
AB  - OBJECTIVE: This paper aimed to determine the standardised incidence ratio (SIR)
      of malignant pleural mesothelioma (MPM) in workers exposed to asbestos in Taiwan.
      METHODS: All workers employed in asbestos-related factories and registered by the
      Bureau of Labour Insurance between 1 March, 1950, and 31 December, 1989, were
      included in the study and were followed from 1 January, 1980, through 31
      December, 2009. Incident cases of all cancers, including MPM (ICD-9 code: 163),
      were obtained from the Taiwan Cancer Registry. SIRs were calculated based on
      comparison with the incidence rate of the general population of Taiwan and
      adjusted for age, calendar period, sex, and duration of employment. RESULTS: The
      highest SIR of MPM was found for male workers first employed before 1979, with a
      time since first employment more than 30 years (SIR 4.52, 95% CI: 2.25-8.09).
      After consideration of duration of employment, the SIR for male MPM was 5.78 (95%
      CI: 1.19-16.89) for the workers employed for more than 20 years in asbestos
      related factories. CONCLUSIONS: This study corroborates the association between
      occupational asbestos exposure and MPM. The highest risk of MPM was found among
      male asbestos workers employed before 1979 and working for more than 20 years in
      asbestos-related factories.

PMID- 26290872
TI  - Cleft Palate, Interdisciplinary Diagnosis, and Treatment.

PMID- 26290870
TI  - Identification of Gene Biomarkers for Distinguishing Small-Cell Lung Cancer from
      Non-Small-Cell Lung Cancer Using a Network-Based Approach.
AB  - Lung cancer consists of two main subtypes: small-cell lung cancer (SCLC) and non
      small-cell lung cancer (NSCLC) that are classified according to their
      physiological phenotypes. In this study, we have developed a network-based
      approach to identify molecular biomarkers that can distinguish SCLC from NSCLC.
      By identifying positive and negative coexpression gene pairs in normal lung
      tissues, SCLC, or NSCLC samples and using functional association information from
      the STRING network, we first construct a lung cancer-specific gene association
      network. From the network, we obtain gene modules in which genes are highly
      functionally associated with each other and are either positively or negatively
      coexpressed in the three conditions. Then, we identify gene modules that not only
      are differentially expressed between cancer and normal samples, but also show
      distinctive expression patterns between SCLC and NSCLC. Finally, we select genes
      inside those modules with discriminating coexpression patterns between the two
      lung cancer subtypes and predict them as candidate biomarkers that are of
      diagnostic use. 

PMID- 26290873
TI  - Incidence and Predictors of New-Onset Silent Atrial Fibrillation after Coronary
      Artery Bypass Graft Surgery.
AB  - AIMS: We investigated the incidence, risk factors, and prognostic impact of
      silent atrial fibrillation (AF) after coronary artery bypass graft (CABG)
      surgery. METHODS: This observational study prospectively included 100 patients
      referred for CABG surgery. Holter ECG monitoring was used to record every
      arrhythmic event for 7 days. AF was defined as at least one episode >30 s.
      Episodes recorded on Holter ECG monitoring but not clinically identified were
      classified as silent AF. RESULTS: Among 34 patients who developed new-onset AF,
      13 had silent AF. Compared with patients with maintained sinus rhythm (SR),
      silent AF patients had a significantly higher logistic EuroSCORE (2.9 (1.5-5.2)
      versus 2.3 (1.4-3.7), p = 0.017) and were more likely to have previous sleep
      apnea (31% versus 8%, p = 0.016) and left atrial diameter >45 mm (36% versus 5%,
      p = 0.002). At one-year follow-up, 30% of silent AF patients had developed
      symptomatic AF versus 7% in the SR group (p = 0.03) and 11% in the clinical AF
      group (p = 0.21). CONCLUSION: After CABG surgery, silent AF is common and may be
      associated with a higher incidence of recurrences at one-year follow-up than
      clinical AF. Improved screening for silent AF may help to reduce thromboembolic
      events in this high-risk population.

PMID- 26290875
TI  - Effect of Meteorological and Geographical Factors on the Epidemics of Hand, Foot,
      and Mouth Disease in Island-Type Territory, East Asia.
AB  - Hand, foot, and mouth disease (HFMD) has threatened East Asia for more than three
      decades and has become an important public health issue owing to its severe
      sequelae and mortality among children. The lack of effective treatment and
      vaccine for HFMD highlights the urgent need for efficiently integrated early
      warning surveillance systems in the region. In this study, we try to integrate
      the available surveillance and weather data in East Asia to elucidate possible
      spatiotemporal correlations and weather conditions among different areas from low
      to high latitude. The general additive model (GAM) was applied to understand the
      association between HFMD and latitude, as well as meteorological factors for
      islands in East Asia, namely, Japan, Taiwan, Hong Kong, and Singapore, from 2012
      to 2014. The results revealed that latitude was the most important explanatory
      factor associated with the timing and amplitude of HFMD epidemics (P < 0.0001).
      Meteorological factors including higher dew point, lower visibility, and lower
      wind speed were significantly associated with the rise of epidemics (P < 0.01).
      In summary, weather conditions and geographic location could play some role in
      affecting HFMD epidemics. Regional integrated surveillance of HFMD in East Asia
      is needed for mitigating the disease risk. 

PMID- 26290874
TI  - Peripheral Administration of Tumor Necrosis Factor-Alpha Induces
      Neuroinflammation and Sickness but Not Depressive-Like Behavior in Mice.
AB  - Clinical observations indicate that activation of the TNF-alpha system may
      contribute to the development of inflammation-associated depression. Here, we
      tested the hypothesis that systemic upregulation of TNF-alpha induces
      neuroinflammation and behavioral changes relevant to depression. We report that a
      single intraperitoneal injection of TNF-alpha in mice increased serum and brain
      levels of the proinflammatory mediators TNF-alpha, IL-6, and MCP-1, in a dose-
      and time-dependent manner, but not IL-1beta. Protein levels of the anti
      inflammatory cytokine IL-10 increased in serum but not in the brain. The
      transient release of immune molecules was followed by glial cell activation as
      indicated by increased astrocyte activation in bioluminescent Gfap-luc mice and
      elevated immunoreactivity against the microglial marker Iba1 in the dentate gyrus
      of TNF-alpha-challenged mice. Additionally, TNF-alpha-injected mice were
      evaluated in a panel of behavioral tests commonly used to study sickness and
      depressive-like behavior in rodents. Our behavioral data imply that systemic
      administration of TNF-alpha induces a strong sickness response characterized by
      reduced locomotor activity, decreased fluid intake, and body weight loss.
      Depressive-like behavior could not be separated from sickness at any of the time
      points studied. Together, these results demonstrate that peripheral TNF-alpha
      affects the central nervous system at a neuroimmune and behavioral level. 

PMID- 26290876
TI  - Challenges and Strategies of Laboratory Diagnosis for Newly Emerging Influenza
      Viruses in Taiwan: A Decade after SARS.
AB  - Since the first case of severe acute respiratory syndrome (SARS) in Taiwan was
      identified in March 2003, viral respiratory infections, in particular the
      influenza virus, have become a national public health concern. Taiwan would face
      a serious threat of public health problems if another SARS epidemic overlapped
      with a flu outbreak. After SARS, the Taiwan Centers for Disease Control
      accelerated and strengthened domestic research on influenza and expanded the
      exchange of information with international counterparts. The capacity of
      influenza A to cross species barriers presents a potential threat to human
      health. Given the mutations of avian flu viruses such as H7N9, H6N1, and H10N8,
      all countries, including Taiwan, must equip themselves to face a possible
      epidemic or pandemic. Such preparedness requires global collaboration. 

PMID- 26290877
TI  - Absence of the mecA Gene in Methicillin Resistant Staphylococcus aureus Isolated
      from Different Clinical Specimens in Shendi City, Sudan.
AB  - Absolute dependence on mecA gene as the defining standard in determining the
      resistance of S. aureus to methicillin became the subject of distrust by many
      researchers. The present study aimed to determine the frequency of mecA gene in
      methicillin resistant S. aureus (MRSA) isolates using polymerase chain reaction
      and to correlate its presence to conventional method. In this regard, two hundred
      S. aureus isolates were collected from patients with different diseases attending
      different hospitals in Shandi City, Sudan. Phenotypic Kirby-Bauer method
      confirmed the existence of methicillin resistant S. aureus in 61.5% of the
      subjected isolates with MICs ranging from 4 MUg/mL to 256 MUg/mL when using E
      test. However, when amplifying a 310 bp fragment of the mecA gene by PCR, twelve
      out of the 123 MRSA isolates (9.8%) were mecA negative, whereas all the 77
      methicillin sensitive S. aureus (MSSA) were mecA negative. In conclusion, this
      study drew attention to the credibility of the mecA gene and its usefulness in
      the detection of all MRSA strains without referring to the traditional methods.
      Hence, it is highly recommended to consider alternative mechanisms for beta
      lactam resistance that may compete with mecA gene in the emergence of MRSA
      phenomenon in the community.

PMID- 26290878
TI  - Insulin Resistance, Type 1 and Type 2 Diabetes, and Related Complications 2015.

PMID- 26290879
TI  - Association Analysis of Genetic Variants with Type 2 Diabetes in a Mongolian
      Population in China.
AB  - The large scale genome wide association studies (GWAS) have identified
      approximately 80 single nucleotide polymorphisms (SNPs) conferring susceptibility
      to type 2 diabetes (T2D). However, most of these loci have not been replicated in
      diverse populations and much genetic heterogeneity has been observed across
      ethnic groups. We tested 28 SNPs previously found to be associated with T2D by
      GWAS in a Mongolian sample of Northern China (497 diagnosed with T2D and 469
      controls) for association with T2D and diabetes related quantitative traits. We
      replicated T2D association of 11 SNPs, namely, rs7578326 (IRS1), rs1531343
      (HMGA2), rs8042680 (PRC1), rs7578597 (THADA), rs1333051 (CDKN2), rs6723108
      (TMEM163), rs163182 and rs2237897 (KCNQ1), rs1387153 (MTNR1B), rs243021 (BCL11A),
      and rs10229583 (PAX4) in our sample. Further, we showed that risk allele of the
      strongest T2D associated SNP in our sample, rs757832 (IRS1), is associated with
      increased level of TG. We observed substantial difference of T2D risk allele
      frequency between the Mongolian sample and the 1000G Caucasian sample for a few
      SNPs, including rs6723108 (TMEM163) whose risk allele reaches near fixation in
      the Mongolian sample. Further study of genetic architecture of these variants in
      susceptibility of T2D is needed to understand the role of these variants in
      heterogeneous populations. 

PMID- 26290880
TI  - Fluorescent foci quantitation for high-throughput analysis.
AB  - A number of cellular proteins localize to discrete foci within cells, for example
      DNA repair proteins, microtubule organizing centers, P bodies or kinetochores. It
      is often possible to measure the fluorescence emission from tagged proteins
      within these foci as a surrogate for the concentration of that specific protein.
      We wished to develop tools that would allow quantitation of fluorescence foci
      intensities in high-throughput studies. As proof of principle we have examined
      the kinetochore, a large multi-subunit complex that is critical for the accurate
      segregation of chromosomes during cell division. Kinetochore perturbations lead
      to aneuploidy, which is a hallmark of cancer cells. Hence, understanding
      kinetochore homeostasis and regulation are important for a global understanding
      of cell division and genome integrity. The 16 budding yeast kinetochores
      colocalize within the nucleus to form a single focus. Here we have created a set
      of freely-available tools to allow high-throughput quantitation of kinetochore
      foci fluorescence. We use this 'FociQuant' tool to compare methods of kinetochore
      quantitation and we show proof of principle that FociQuant can be used to
      identify changes in kinetochore protein levels in a mutant that affects
      kinetochore function. This analysis can be applied to any protein that forms
      discrete foci in cells.

PMID- 26290881
TI  - Applied Use of Composite Quality Measures for EHR-enabled Practices.
AB  - INTRODUCTION: The Primary Care Information Project (PCIP) of the New York City
      Department of Health and Mental Hygiene has been assisting providers to implement
      health information technology such as electronic health records (EHRs) since its
      founding in 2005. Currently, all practices affiliated with PCIP are offered
      technical support services in order to improve the use of the EHR. We studied the
      performance of clinical practices on EHR-derived Composite Quality Measures
      (CQMs) over time. Because specific EHR functionalities are important to
      calculating the quality measures, we hypothesize that performance on each of the
      CQMs will differ according to the EHR functionalities, and that this can inform
      the process of developing targeted technical assistance for the practices.
      METHODS: We created four CQMs: (1) Screening, (2) Assessment, (3) Control-BP, and
      (4) Control-Other. Using data from 93 practices, we identified three tertiles of
      CQM performance (premier, average, and low tiers) for each measure. A scatterplot
      of CQMs in 2010 versus 2011 was used to examine the individual movement of
      practices by tier. A dependent t-test compared the change in mean CQMs, and a chi
      square test examined the association between the score and performance tier
      changes. RESULTS: Over a one-year period, low tier practices demonstrated the
      highest gains, average tier practices had modest gains, and premier tier
      practices had gains in some measures, but losses in others. On the Screening CQM
      70 percent of practices remained within the same tier, with 60 percent on
      Assessment, 52 percent on Control-BP, and 38 percent on Control-Other; the
      Control-Other group showed the greatest improvement. DISCUSSION: By considering
      EHR functionalities associated with each of the four CQMs, we suggest that
      technical assistance can be better targeted to low-tier performing practices. In
      addition, there is still the potential for improvement over time at practices
      more familiar with key functionalities.

PMID- 26290882
TI  - The Challenges of Data Quality Evaluation in a Joint Data Warehouse.
AB  - INTRODUCTION: The use of clinically derived data from electronic health records
      (EHRs) and other electronic clinical systems can greatly facilitate clinical
      research as well as operational and quality initiatives. One approach for making
      these data available is to incorporate data from different sources into a joint
      data warehouse. When using such a data warehouse, it is important to understand
      the quality of the data. The primary objective of this study was to determine the
      completeness and concordance of common types of clinical data available in the
      Knowledge Program (KP) joint data warehouse, which contains feeds from several
      electronic systems including the EHR. METHODS: A manual review was performed of
      specific data elements for 250 patients from an EHR, and these were compared with
      corresponding elements in the KP data warehouse. Completeness and concordance
      were calculated for five categories of data including demographics, vital signs,
      laboratory results, diagnoses, and medications. RESULTS: In general, data
      elements for demographics, vital signs, diagnoses, and laboratory results were
      present in more cases in the source EHR compared to the KP. When data elements
      were available in both sources, there was a high concordance. In contrast, the KP
      data warehouse documented a higher prevalence of deaths and medications compared
      to the EHR. DISCUSSION: Several factors contributed to the discrepancies between
      data in the KP and the EHR-including the start date and frequency of data feeds
      updates into the KP, inability to transfer data located in nonstructured formats
      (e.g., free text or scanned documents), as well as incomplete and missing data
      variables in the source EHR. CONCLUSION: When evaluating the quality of a data
      warehouse with multiple data sources, assessing completeness and concordance
      between data set and source data may be better than designating one to be a gold
      standard. This will allow the user to optimize the method and timing of data
      transfer in order to capture data with better accuracy.

PMID- 26290883
TI  - Development of an Algorithm to Classify Colonoscopy Indication from Coded Health
      Care Data.
AB  - INTRODUCTION: Electronic health data are potentially valuable resources for
      evaluating colonoscopy screening utilization and effectiveness. The ability to
      distinguish screening colonoscopies from exams performed for other purposes is
      critical for research that examines factors related to screening uptake and
      adherence, and the impact of screening on patient outcomes, but distinguishing
      between these indications in secondary health data proves challenging. The
      objective of this study is to develop a new and more accurate algorithm for
      identification of screening colonoscopies using electronic health data. METHODS:
      Data from a case-control study of colorectal cancer with adjudicated colonoscopy
      indication was used to develop logistic regression-based algorithms. The proposed
      algorithms predict the probability that a colonoscopy was indicated for
      screening, with variables selected for inclusion in the models using the Least
      Absolute Shrinkage and Selection Operator (LASSO). RESULTS: The algorithms had
      excellent classification accuracy in internal validation. The primary, restricted
      model had AUC= 0.94, sensitivity=0.91, and specificity=0.82. The secondary,
      extended model had AUC=0.96, sensitivity=0.88, and specificity=0.90. DISCUSSION:
      The LASSO approach enabled estimation of parsimonious algorithms that identified
      screening colonoscopies with high accuracy in our study population. External
      validation is needed to replicate these results and to explore the performance of
      these algorithms in other settings.

PMID- 26290884
TI  - Augmenting Predictive Modeling Tools with Clinical Insights for Care Coordination
      Program Design and Implementation.
AB  - CONTEXT: The Center for Medicare and Medicaid Innovation (CMMI) awarded Denver
      Health's (DH) integrated, safety net health care system $19.8 million to
      implement a "population health" approach into the delivery of primary care. This
      major practice transformation builds on the Patient Centered Medical Home (PCMH)
      and Wagner's Chronic Care Model (CCM) to achieve the "Triple Aim": improved
      health for populations, care to individuals, and lower per capita costs. CASE
      DESCRIPTION: This paper presents a case study of how DH integrated published
      predictive models and front-line clinical judgment to implement a clinically
      actionable, risk stratification of patients. This population segmentation
      approach was used to deploy enhanced care team staff resources and to tailor care
      management services to patient need, especially for patients at high risk of
      avoidable hospitalization. Developing, implementing, and gaining clinical
      acceptance of the Health Information Technology (HIT) solution for patient risk
      stratification was a major grant objective. FINDINGS: In addition to describing
      the Information Technology (IT) solution itself, we focus on the leadership and
      organizational processes that facilitated its multidisciplinary development and
      ongoing iterative refinement, including the following: team composition, target
      population definition, algorithm rule development, performance assessment, and
      clinical-workflow optimization. We provide examples of how dynamic business
      intelligence tools facilitated clinical accessibility for program design
      decisions by enabling real-time data views from a population perspective down to
      patient-specific variables. CONCLUSIONS: We conclude that population segmentation
      approaches that integrate clinical perspectives with predictive modeling results
      can better identify high opportunity patients amenable to medical home-based,
      enhanced care team interventions.

PMID- 26290885
TI  - Back to the Bedside: Developing a Bedside Aid for Concussion and Brain Injury
      Decisions in the Emergency Department.
AB  - CONTEXT: Current information-rich electronic health record (EHR) interfaces
      require large, high-resolution screens running on desktop computers. This
      interface compromises the provider's already limited time at the bedside by
      physically separating the patient from the doctor. The case study presented here
      describes a patient-centered clinical decision support (CDS) design process that
      aims to bring the physician back to the bedside by integrating a patient decision
      aid with CDS for shared use by the patient and provider on a touchscreen tablet
      computer for deciding whether or not to obtain a CT scan for minor head injury in
      the emergency department, a clinical scenario that could benefit from CDS but has
      failed previous implementation attempts. CASE DESCRIPTION: This case study
      follows the user-centered design (UCD) approach to build a bedside aid that is
      useful and usable, and that promotes shared decision-making between patients and
      their providers using a tablet computer at the bedside. The patient-centered
      decision support design process focuses on the prototype build using agile
      software development, but also describes the following: (1) the requirement
      gathering phase including triangulated qualitative research (focus groups and
      cognitive task analysis) to understand current challenges, (2) features for
      patient education, the physician, and shared decision-making, (3) system
      architecture and technical requirements, and (4) future plans for formative
      usability testing and field testing. LESSONS LEARNED: We share specific lessons
      learned and general recommendations from critical insights gained in the patient
      centered decision support design process about early stakeholder engagement, EHR
      integration, external expert feedback, challenges to two users on a single
      device, project management, and accessibility. CONCLUSIONS: Successful
      implementation of this tool will require seamless integration into the provider's
      workflow. This protocol can create an effective interface for shared decision
      making and safe resource reduction at the bedside in the austere and dynamic
      clinical environment of the ED and is generalizable for these purposes in other
      clinical environments as well.

PMID- 26290886
TI  - TeenBP: Development and Piloting of an EHR-Linked Clinical Decision Support
      System to Improve Recognition of Hypertension in Adolescents.
AB  - CONTEXT: Blood pressure (BP) is routinely measured in children and adolescents
      during primary care visits. However, elevated BP or hypertension is frequently
      not diagnosed or evaluated further by primary care providers. Barriers to
      recognition include lack of clinician buy-in, competing priorities, and
      complexity of the standard BP tables. CASE DESCRIPTION: We have developed and
      piloted TeenBP- a web-based, electronic health record (EHR) linked system
      designed to improve recognition of prehypertension and hypertension in
      adolescents during primary care visits. MAJOR THEMES: Important steps in
      developing TeenBP included the following: review of national BP guidelines,
      consideration of clinic workflow, engagement of clinical leaders, and evaluation
      of the impact on clinical sites. Use of a web-based platform has facilitated
      updates to the TeenBP algorithm and to the message content. In addition, the web
      based platform has allowed for development of a sophisticated display of patient
      specific information at the point of care. In the TeenBP pilot, conducted at a
      single pediatric and family practice site with six clinicians, over a five-month
      period, more than half of BPs in the hypertensive range were clinically
      recognized. Furthermore, in this small pilot the TeenBP clinical decision support
      (CDS) was accepted by providers and clinical staff. Effectiveness of the TeenBP
      CDS will be determined in a two-year cluster-randomized clinical trial, currently
      underway at 20 primary care sites. CONCLUSION: Use of technology to extract and
      display clinically relevant data stored within the EHR may be a useful tool for
      improving recognition of adolescent hypertension during busy primary care visits.
      In the future, the methods developed specifically for TeenBP are likely to be
      translatable to a wide range of acute and chronic issues affecting children and
      adolescents.

PMID- 26290887
TI  - Improving Clinical Workflow in Ambulatory Care: Implemented Recommendations in an
      Innovation Prototype for the Veteran's Health Administration.
AB  - INTRODUCTION: Human factors workflow analyses in healthcare settings prior to
      technology implemented are recommended to improve workflow in ambulatory care
      settings. In this paper we describe how insights from a workflow analysis
      conducted by NIST were implemented in a software prototype developed for a
      Veteran's Health Administration (VHA) VAi2 innovation project and associated
      lessons learned. METHODS: We organize the original recommendations and associated
      stages and steps visualized in process maps from NIST and the VA's lessons
      learned from implementing the recommendations in the VAi2 prototype according to
      four stages: 1) before the patient visit, 2) during the visit, 3) discharge, and
      4) visit documentation. NIST recommendations to improve workflow in ambulatory
      care (outpatient) settings and process map representations were based on
      reflective statements collected during one-hour discussions with three
      physicians. The development of the VAi2 prototype was conducted initially
      independently from the NIST recommendations, but at a midpoint in the process
      development, all of the implementation elements were compared with the NIST
      recommendations and lessons learned were documented. FINDINGS: Story-based
      displays and templates with default preliminary order sets were used to support
      scheduling, time-critical notifications, drafting medication orders, and
      supporting a diagnosis-based workflow. These templates enabled customization to
      the level of diagnostic uncertainty. Functionality was designed to support
      cooperative work across interdisciplinary team members, including shared
      documentation sessions with tracking of text modifications, medication lists, and
      patient education features. Displays were customized to the role and included
      access for consultants and site-defined educator teams. DISCUSSION: Workflow,
      usability, and patient safety can be enhanced through clinician-centered design
      of electronic health records. The lessons learned from implementing NIST
      recommendations to improve workflow in ambulatory care using an EHR provide a
      first step in moving from a billing-centered perspective on how to maintain
      accurate, comprehensive, and up-to-date information about a group of patients to
      a clinician-centered perspective. These recommendations point the way towards a
      "patient visit management system," which incorporates broader notions of
      supporting workload management, supporting flexible flow of patients and tasks,
      enabling accountable distributed work across members of the clinical team, and
      supporting dynamic tracking of steps in tasks that have longer time
      distributions.

PMID- 26290889
TI  - Initial Usability and Feasibility Evaluation of a Personal Health Record-Based
      Self-Management System for Older Adults.
AB  - INTRODUCTION: Electronic personal health record-based (ePHR-based) self
      management systems can improve patient engagement and have an impact on health
      outcomes. In order to realize the benefits of these systems, there is a need to
      develop and evaluate heath information technology from the same theoretical
      underpinnings. METHODS: Using an innovative usability approach based in human
      centered distributed information design (HCDID), we tested an ePHR-based falls
      prevention self-management system-Self-Assessment via a Personal Health Record
      (i.e., SAPHeR)-designed using HCDID principles in a laboratory. And we later
      evaluated SAPHeR's use by community-dwelling older adults at home. RESULTS: The
      innovative approach used in this study supported the analysis of four components:
      tasks, users, representations, and functions. Tasks were easily learned and
      features such as text-associated images facilitated task completion. Task
      performance times were slow, however user satisfaction was high. Nearly seven out
      of every ten features desired by design participants were evaluated in our
      usability testing of the SAPHeR system. The in vivo evaluation suggests that
      older adults could improve their confidence in performing indoor and outdoor
      activities after using the SAPHeR system. DISCUSSION/CONCLUSION: We have applied
      an innovative consumer-usability evaluation. Our approach addresses the
      limitations of other usability testing methods that do not utilize consistent
      theoretically based methods for designing and testing technology. We have
      successfully demonstrated the utility of testing consumer technology use across
      multiple components (i.e., task, user, representational, functional) to evaluate
      the usefulness, usability, and satisfaction of an ePHR-based self-management
      system.

PMID- 26290890
TI  - A Multistep Maturity Model for the Implementation of Electronic and Computable
      Diagnostic Clinical Prediction Rules (eCPRs).
AB  - INTRODUCTION: The use of Clinical Prediction Rules (CPRs) has been advocated as
      one way of implementing actionable evidence-based rules in clinical practice. The
      current highly manual nature of deriving CPRs makes them difficult to use and
      maintain. Addressing the known limitations of CPRs requires implementing more
      flexible and dynamic models of CPR development. We describe the application of
      Information and Communication Technology (ICT) to provide a platform for the
      derivation and dissemination of CPRs derived through analysis and continual
      learning from electronic patient data. MODEL COMPONENTS: We propose a multistep
      maturity model for constructing electronic and computable CPRs (eCPRs). The model
      has six levels - from the lowest level of CPR maturity (literaturebased CPRs) to
      a fully electronic and computable service-oriented model of CPRs that are
      sensitive to specific demographic patient populations. We describe examples of
      implementations of the core model components - focusing on CPR representation,
      interoperability, electronic dissemination, CPR learning, and user interface
      requirements. CONCLUSION: The traditional focus on derivation and narrow
      validation of CPRs has severely limited their wider acceptance. The evolution and
      maturity model described here outlines a progression toward eCPRs consistent with
      the vision of a learning health system (LHS) - using central repositories of CPR
      knowledge, accessible open standards, and generalizable models to avoid
      repetition of previous work. This is useful for developing more ambitious
      strategies to address limitations of the traditional CPR development life cycle.
      The model described here is a starting point for promoting discussion about what
      a more dynamic CPR development process should look like.

PMID- 26290891
TI  - EHR-based Visualization Tool: Adoption Rates, Satisfaction, and Patient Outcomes.
AB  - BACKGROUND: Electronic health records (EHRs) have the potential to enhance
      patient-provider communication and improve patient outcomes. However, in order to
      impact patient care, clinical decision support (CDS) and communication tools
      targeting such needs must be integrated into clinical workflow and be flexible
      with regard to the changing health care landscape. DESIGN: The Stroke Prevention
      in Healthcare Delivery Environments (SPHERE) team developed and implemented the
      SPHERE tool, an EHR-based CDS visualization, to enhance patient-provider
      communication around cardiovascular health (CVH) within an outpatient primary
      care setting of a large academic medical center. IMPLEMENTATION: We describe our
      successful CDS alert implementation strategy and report adoption rates. We also
      present results of a provider satisfaction survey showing that the SPHERE tool
      delivers appropriate content in a timely manner. Patient outcomes following
      implementation of the tool indicate one-year improvements in some CVH metrics,
      such as body mass index and diabetes. DISCUSSION: Clinical decision-making and
      practices change rapidly and in parallel to simultaneous changes in the health
      care landscape and EHR usage. Based on these observations and our preliminary
      results, we have found that an integrated, extensible, and workflow-aware CDS
      tool is critical to enhancing patient-provider communications and influencing
      patient outcomes.

PMID- 26290888
TI  - A Framework for Usable and Effective Clinical Decision Support: Experience from
      the iCPR Randomized Clinical Trial.
AB  - INTRODUCTION: The promise of Clinical Decision Support (CDS) has always been to
      transform patient care and improve patient outcomes through the delivery of
      timely and appropriate recommendations that are patient specific and, more often
      than not, are appropriately actionable. However, the users of CDS-providers-are
      frequently bombarded with inappropriate and inapplicable CDS that often are not
      informational, not integrated into the workflow, not patient specific, and that
      may present out of date and irrelevant recommendations. METHODS: The integrated
      clinical prediction rule (iCPR) project was a randomized clinical trial (RCT)
      conducted to determine if a novel form of CDS, i.e., clinical prediction rules
      (CPRs), could be efficiently integrated into workflow and result in changes in
      outcomes (e.g., antibiotic ordering) when embedded within a commercial electronic
      health record (EHR). We use the lessons learned from the iCPR project to
      illustrate a framework for constructing usable, useful, and effective actionable
      CDS while employing off-the-shelf functionality in a production system.
      Innovations that make up the framework combine the following: (1) active and
      actionable decision support, (2) multiple rounds of usability testing with
      iterative development for user acceptance, (3) numerous context sensitive
      triggers, (4) dedicated training and support for users of the CDS tool for user
      adoption, and (5) support from clinical and administrative leadership. We define
      "context sensitive triggers" as being workflow events (i.e., context) that result
      in a CDS intervention. DISCUSSION: Success of the framework can be measured by
      CDS adoption (i.e., intervention is being used), acceptance (compliance with
      recommendations), and clinical outcomes (where appropriate). This framework may
      have broader implications for the deployment of Health Information Technology
      (HIT). RESULTS AND CONCLUSION: iCPR was well adopted(57.4% of users) and accepted
      (42.7% of users). Usability testing identified and fixed many issues before the
      iCPR RCT. The level of leadership support and clinical guidance for iCPR was key
      in establishing a culture of acceptance for both the tool and its recommendations
      contributing to adoption and acceptance. The dedicated training and support lead
      to the majority of the residents reporting a high level of comfort with both iCPR
      tools strep pharyngitis (64.4 percent) and pneumonia (62.7 percent) as well as a
      high likelihood of using the tools in the future. A surprising framework addition
      resulted from usability testing: context sensitive triggers.

PMID- 26290892
TI  - Teaching Evidence Assimilation for Collaborative Health Care (TEACH) 2009-2014:
      Building Evidence-Based Capacity within Health Care Provider Organizations.
AB  - BACKGROUND: Clinical guidelines, prediction tools, and computerized decision
      support (CDS) are underutilized outside of research contexts, and conventional
      teaching of evidence-based practice (EBP) skills fails to change practitioner
      behavior. Overcoming these challenges requires traversing practice, policy, and
      implementation domains. In this article, we describe a program's conceptual
      design, the results of institutional participation, and the program's evolution.
      Next steps include integration of instruction in principles of CDS. CONCEPTUAL
      MODEL: Teaching Evidence Assimilation for Collaborative Health Care (TEACH) is a
      multidisciplinary annual conference series involving on- and off-site trainings
      and facilitation within health care provider organizations (HPOs). Separate
      conference tracks address clinical policy and guideline development,
      implementation science, and foundational EBP skills. The implementation track
      uses a model encompassing problem delineation, identifying knowing-doing gaps,
      synthesizing evidence to address those gaps, adapting guidelines for local use,
      assessing implementation barriers, measuring outcomes, and sustaining evidence
      use. Training in CDS principles is an anticipated component within this track.
      Within participating organizations, the program engages senior administration,
      middle management, and frontline care providers. On-site care improvement
      projects serve as vehicles for developing ongoing, sustainable capabilities.
      TEACH facilitators conduct on-site workshops to enhance project development,
      integration of stakeholder engagement and decision support. Both on- and off-site
      components emphasize narrative skills and shared decision-making. EXPERIENCE:
      Since 2009, 430 participants attended TEACH conferences. Delegations from five
      centers attended an initial series of three conferences. Improvement projects
      centered on stroke care, hospital readmissions, and infection control. Successful
      implementation efforts were characterized by strong support of senior
      administration, involvement of a broad multidisciplinary constituency within the
      organization, and on-site facilitation on the part of TEACH faculty. Involvement
      of nursing management at the senior faculty level led to increased presence of
      nursing and other disciplines at subsequent conferences. CONCLUSIONS: A
      multidisciplinary and multifaceted approach to on- and off-site training and
      facilitation may lead to enhanced use of research to improve the quality of care
      within HPOs. Such training may provide valuable contextual grounding for
      effective use of CDS within such organizations.

PMID- 26290893
TI  - Using Qualitative Methods to Create a Home Health Web Application User Interface
      for Patients with Low Computer Proficiency.
AB  - INTRODUCTION: Despite the investment in public reporting for a number of
      healthcare settings, evidence indicates that consumers do not routinely use
      available data to select providers. This suggests that existing reports do not
      adequately incorporate recommendations for consumer-facing reports or web
      applications. METHODS: Healthcentric Advisors and Brown University undertook a
      multi-phased approach to create a consumer-facing home health web application in
      Rhode Island. This included reviewing the evidence base review to identify design
      recommendations and then creating a paper prototype and wireframe. We performed
      qualitative research to iteratively test our proposed user interface with two
      user groups, home health consumers and hospital case managers, refining our
      design to create the final web application. RESULTS: To test our prototype, we
      conducted two focus groups, with a total of 13 consumers, and 28 case manager
      interviews. Both user groups responded favorably to the prototype, with the
      majority commenting that they felt this type of tool would be useful. Case
      managers suggested revisions to ensure the application conformed to laws
      requiring Medicare patients to have the freedom to choose among providers and
      could be incorporated into hospital workflow. After incorporating changes and
      creating the wireframe, we conducted usability testing interviews with 14 home
      health consumers and six hospital case managers. We found that consumers needed
      prompting to navigate through the wireframe; they demonstrated confusion through
      both their words and body language. As a result, we modified the web
      application's sequence, navigation, and function to provide additional
      instructions and prompts. DISCUSSION: Although we designed our web application
      for low literacy and low health literacy, using recommendations from the evidence
      base, we overestimated the extent to which older adults were familiar with using
      computers. Some of our key learnings and recommendations run counter to general
      web design principles, leading us to believe that such guidelines need to be
      adapted for this user group. As web applications proliferate, it is important to
      ensure those who are most vulnerable-who have the least knowledge and the lowest
      literacy, health literacy, and computer proficiency-can access, understand, and
      use them. CONCLUSIONS: In order for the investment in public reporting to produce
      value, consumer-facing web applications need to be designed to address end users'
      unique strengths and limitations. Our findings may help others to build consumer
      facing tools or technology targeted to a predominantly older population. We
      encourage others designing consumer-facing web technologies to critically
      evaluate their assumptions about user interface design, particularly if they are
      designing tools for older adults, and to test products with their end users.

PMID- 26290894
TI  - CDS, UX, and System Redesign - Promising Techniques and Tools to Bridge the
      Evidence Gap.
AB  - INTRODUCTION: In this special issue of eGEMs, we explore the struggles related to
      bringing evidence into day-to-day practice, what I define as the "evidence gap."
      We are all aware of high quality evidence in the form of guidelines, randomized
      clinical trials for treatments and diagnostic tests, and clinical prediction
      rules, which are all readily available online. We also know that electronic
      health records (EHRs) are now ubiquitous in health care and in most practices
      across the country. How we marry this high quality evidence and the practice of
      medicine through effective decision support is a major challenge. ABOUT THE
      ISSUE: All of the articles in this issue explore, in some fashion, CDS systems
      and how we can best bring providers and their work environment to the evidence.
      We are at the very early stages of the science of usability. Much more research
      and funding is needed in this area if we hope to improve the dissemination and
      implementation of evidence in practice. While the featured examples, techniques,
      and tools in the special issue are a promising start to improving usability and
      CDS, many of the papers highlight current gaps in knowledge and a great need for
      generalizable approaches. The great promise is for "learning" approaches to
      generate new evidence and to integrate this evidence in reliable, patient
      centered ways at scale using new technology. Closing the evidence gap is a real
      possibility, but only if the community works together to innovate and invest in
      research on the best ways to disseminate, communicate, and implement evidence in
      practice.

PMID- 26290895
TI  - Reply to comment on: A novel dysferlin mutant pseudoexon bypassed with antisense
      oligonucleotides.

PMID- 26290896
TI  - PPARdelta and PGE2 signaling pathways communicate and connect inflammation to
      colorectal cancer.
AB  - The nuclear hormone receptor peroxisome proliferator-activated receptor delta
      (PPARdelta) is a ligand-dependent transcription factor that is involved in fatty
      acid metabolism, obesity, wound healing, inflammation, and cancer. Despite
      decades of research, the role of PPARdelta in inflammation and colorectal cancer
      remains unclear and somewhat controversial. Our recent work presented the first
      genetic evidence demonstrating that PPARdelta is required for chronic colonic
      inflammation and colitis-associated carcinogenesis. We also found that a
      PPARdelta downstream pathway, namely the COX-2-derived PGE2 signaling, mediated
      crosstalk between tumor epithelial cells and macrophages to promote chronic
      inflammation and colitis-associated tumor genesis. In this brief review, we
      summarize recent studies on the role of PPARdelta in inflammatory bowel disease
      (IBD) and colorectal cancer (CRC) and highlight recent advances in our
      understanding of how PPARdelta and COX-2-drevided PGE2 signaling coordinately
      promote chronic colonic inflammation and colitis-associate tumorigenesis.
      Elucidating the role of PPARdelta in inflammation and CRC may provide a rationale
      for development of PPARdelta antagonists as new therapeutic agents in treatment
      of IBD and CRC.

PMID- 26290897
TI  - How to Tell the Truth with Statistics: The Case for Accountable Data Analyses in
      Team-based Science.
AB  - Data analysis is essential to translational medicine, epidemiology, and the
      scientific process. Although recent advances in promoting reproducibility and
      reporting standards have made some improvements, the data analysis process
      remains insufficiently documented and susceptible to avoidable errors, bias, and
      even fraud. Comprehensively accounting for the full analytical process requires
      not only records of the statistical methodology used, but also records of
      communications among the research team. In this regard, the data analysis process
      can benefit from the principle of accountability that is inherent in other
      disciplines such as clinical practice. We propose a novel framework for capturing
      the analytical narrative called the Accountable Data Analysis Process (ADAP),
      which allows the entire research team to participate in the analysis in a
      supervised and transparent way. The framework is analogous to an electronic
      health record in which the dataset is the "patient" and actions related to the
      dataset are recorded in a project management system. We discuss the design,
      advantages, and challenges in implementing this type of system in the context of
      academic health centers, where team based science increasingly demands
      accountability.

PMID- 26290898
TI  - Space-to-Ground Communication for Columbus: A Quantitative Analysis.
AB  - The astronauts on board the International Space Station (ISS) are only the most
      visible part of a much larger team engaged around the clock in the performance of
      science and technical activities in space. The bulk of such team is scattered
      around the globe in five major Mission Control Centers (MCCs), as well as in a
      number of smaller payload operations centres. Communication between the crew in
      space and the flight controllers at those locations is an essential element and
      one of the key drivers to efficient space operations. Such communication can be
      carried out in different forms, depending on available technical assets and the
      selected operational approach for the activity at hand. This paper focuses on
      operational voice communication and provides a quantitative overview of the
      balance achieved in the Columbus program between collaborative space/ground
      operations and autonomous on-board activity execution. An interpretation of the
      current situation is provided, together with a description of potential future
      approaches for deep space exploration missions. 

PMID- 26290899
TI  - Predicting Metabolic Syndrome Using the Random Forest Method.
AB  - AIMS: This study proposes a computational method for determining the prevalence
      of metabolic syndrome (MS) and to predict its occurrence using the National
      Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria.
      The Random Forest (RF) method is also applied to identify significant health
      parameters. MATERIALS AND METHODS: We used data from 5,646 adults aged between 18
      78 years residing in Bangkok who had received an annual health check-up in 2008.
      MS was identified using the NCEP ATP III criteria. The RF method was applied to
      predict the occurrence of MS and to identify important health parameters
      surrounding this disorder. RESULTS: The overall prevalence of MS was 23.70%
      (34.32% for males and 17.74% for females). RF accuracy for predicting MS in an
      adult Thai population was 98.11%. Further, based on RF, triglyceride levels were
      the most important health parameter associated with MS. CONCLUSION: RF was shown
      to predict MS in an adult Thai population with an accuracy >98% and triglyceride
      levels were identified as the most informative variable associated with MS.
      Therefore, using RF to predict MS may be potentially beneficial in identifying MS
      status for preventing the development of diabetes mellitus and cardiovascular
      diseases.

PMID- 26290900
TI  - Malaria antibodies recruit complement to protect children from the disease.

PMID- 26290901
TI  - PD-1 Inhibitor promising in treatment of triple-negative breast cancer.

PMID- 26290903
TI  - CART-meso immunotherapy improved anti-tumor response in early trial.

PMID- 26290902
TI  - Broadly-neutralizing-antibody treatment suppresses HIV viremia.

PMID- 26290904
TI  - Two Ebola vaccine candidates pass phase 2, three others in phase 1.

PMID- 26290905
TI  - Combination immunotherapy mitigated metastatic melanoma in early trial.

PMID- 26290906
TI  - Tetanus toxoid helps dendritic cell vaccines fight glioblastoma.

PMID- 26290907
TI  - Personalized immunotherapy tested in skin and ovarian cancers.

PMID- 26290908
TI  - Vaccinating boys against HPV can by cost-effective prevention of oropharyngeal 
      cancer.

PMID- 26290909
TI  - Reply to Crunelle et al. about the Article 'A Comparison Between Serum 
      Carbohydrate-Deficient Transferrin and Hair Ethyl Glucuronide in  Detecting
      Chronic Alcohol Consumption in Routine'.

PMID- 26290910
TI  - Author response.

PMID- 26290911
TI  - Comment on "Association between familial  hypercholesterolemia and prevalence  of
      type 2 diabetes mellitus".

PMID- 26290912
TI  - Transparency .

PMID- 26290913
TI  - Healthcare Quality and Safety.

PMID- 26290914
TI  - Using Evidence-Based Practice to Move Beyond Doing Things the Way We Have Always
      Done Them.
AB  - Contemporary health care demands better care for individuals with kidney disease.
      In the quest for the Triple Aim of health care--improving the experience of care,
      improving the health of populations, and reducing per capita costs of health care
      -nephrology nurses can no longer afford to practice the way we have always done.
      Instead, it is critical to consider the best available evidence, personal
      expertise, and patient/family preference when engaging in clinical decision
      making. This article provides the steps to develop an evidence-based project to
      address a clinical problem.

PMID- 26290915
TI  - Exploring Advance Care Planning from the Nephrology Nurse Perspective: A
      Literature Review.
AB  - Advance care planning is a process that engages healthcare providers and patients
      to articulate wishes of patients as their illness progresses. Persons with
      chronic kidney disease require earlier and more frequent advance care planning
      conversations because they are faced with increased co-morbidities and a
      shortened lifespan. This literature review explores the phenomenon of advance
      care planning and the potential factors affecting nephrology nurse engagement in
      these discussions.

PMID- 26290916
TI  - Provisions of the Code of Ethics for Nurses: Interpretive Statements for
      Transplant Nurses.
AB  - Nurses working with patients pre-, during, and post-kidney transplant are faced
      with ethical decisions in every phase of the transplant process. This article
      provides interpretive statements for the nine provisions of the 2015 ANA Code of
      Ethics for Nurses for transplant nurses in facilitating patient-centered decision
      making throughout the transplant process.

PMID- 26290917
TI  - Cardiovascular Risk Factors in Patients on Dialysis.
AB  - Cardiovascular disease (CVD) is the leading cause of death in patients undergoing
      dialysis. This article summarizes identified CVD risk factors, elaborates on how
      risk factors impact patients, and discusses the implications to the nephrology
      community based on the current evidence-based practice.

PMID- 26290918
TI  - Health Literacy in Children with Chronic Kidney Disease and Their Caregivers.
AB  - Poorly controlled co-morbidities associated with pediatric chronic kidney disease
      may be associated with low health literacy skills of caregivers. This article
      explores what is known about health literacy in the home management of patients
      with pediatric chronic kidney disease, and examines caregiver and child literacy
      as it relates to child health outcomes.

PMID- 26290919
TI  - Hemodialysis-Induced Myocardial Stunning: A Review.
AB  - Patients on hemodialysis have a high incidence of cardiac morbidity and
      mortality, and echocardiographic evidence of hemodialysis-related myocardial
      stunning supports a potential link between the hemodialysis treatment itself and
      cardiac sequelae. Fluid removal rates exceeding 13 mL/kg/hour during hemodialysis
      have been implicated in the development of myocardial stunning. Providers caring
      for patients on chronic hemodialysis might improve patient outcomes by the use of
      modified treatment monitoring methods, alternative dialysis delivery methods, and
      enhanced patient education regarding risks of excessive interdialytic weight
      gains.

PMID- 26290920
TI  - Understanding Hypertension in Patients on Hemodialysis.
AB  - Hypertension is very prevalent and poorly controlled in patients on hemodialysis
      (HD), and is a major risk factor for the development of cardiovascular morbidity
      and mortality. The underlying mechanisms of hypertension in patients on HD are
      complex and multifactorial. Nurses need to be knowledge able about the underlying
      pathophysiology, blood pressure (BP) goals, and nonpharmacological and
      pharmacological interventions that can improve BP control during and in between
      HD sessions. This article summarizes the underlying pathophysiology of
      hypertension in patients on HD and reviews the literature about management of
      hypertension in patients with end stage renal disease.

PMID- 26290921
TI  - Where's the Evidence? Care Coordination for Adults with Chronic Kidney Disease.

PMID- 26290940
TI  - Eukaryotic Catalase-Peroxidase: The Role of the Trp-Tyr-Met Adduct in Protein
      Stability, Substrate Accessibility, and Catalysis of Hydrogen Peroxide
      Dismutation.
AB  - Recently, it was demonstrated that bifunctional catalase-peroxidases (KatGs) are
      found not only in archaea and bacteria but also in lower eukaryotes. Structural
      studies and preliminary biochemical data of the secreted KatG from the rice
      pathogen Magnaporthe grisea (MagKatG2) suggested both similar and novel features
      when compared to those of the prokaryotic counterparts studied so far. In this
      work, we demonstrate the role of the autocatalytically formed redox-active Trp140
      Tyr273-Met299 adduct of MagKatG2 in (i) the maintenance of the active site
      architecture, (ii) the catalysis of hydrogen peroxide dismutation, and (iii) the
      protein stability by comparing wild-type MagKatG2 with the single mutants
      Trp140Phe, Tyr273Phe, and Met299Ala. The impact of disruption of the covalent
      bonds between the adduct residues on the spectral signatures and heme cavity
      architecture was small. By contrast, loss of its integrity converts bifunctional
      MagKatG2 to a monofunctional peroxidase of significantly reduced thermal
      stability. It increases the accessibility of ligands due to the increased
      flexibility of the KatG-typical large loop 1 (LL1), which contributes to the
      substrate access channel and anchors at the adduct Tyr. We discuss these data
      with respect to those known from prokaryotic KatGs and in addition present a high
      resolution structure of an oxoiron compound of MagKatG2. 

PMID- 26290941
TI  - Factors Contributing to Recovery From Anesthesia and Postoperative Nausea and
      Vomiting-Reply.

PMID- 26290942
TI  - The Origins of the Notion of Countertransference.
AB  - The aim of this paper is to historically contextualize and analyze the birth and
      early development of the concept of countertransference, introduced by Sigmund
      Freud in 1909. In order to do so, scientific publications will be considered, as
      well as the epistolary and the historical information about the personal
      relationship between Freud and his students, and among his students and some of
      their colleagues and patients. 

PMID- 26290943
TI  - C. G. Jung's Dream of Siegfried: A Psychobiographical Study.
AB  - During the past decades, besides Sigmund Freud, C.G. Jung has been a subject of
      modern psychobiographical investigations. The revealed documents of Jung and
      Sabina Speielrein's relationship remarkably changed the narratives of this
      outstanding story, and it also bears important theoretical consequences. This
      article focuses on Jung's Siegfried-dream found in his autobiography, since it is
      closely related to the Freud-Jung-Spielrein triangle, and can be associated with
      some significant aspects of intellectual history. The text of the dream is
      treated as an Allportian "first-person document" that can be a starting point of
      a psychobiographical investigation.

PMID- 26290944
TI  - Narcissism and Object Relations in Hypochondria.
AB  - Hypochondria remains little studied from a theoretical point of view. Whereas
      psychoanalysts know how difficult it is to handle hypochondriac subjects, the few
      works studying the relationship between patients and physicians resort to a
      cognitive-behavioral approach. These latter conclude that the quality of this
      relationship is more important than the disappearance of the symptoms. The aim of
      this work is to show how psychoanalysis can conceptualize hypochondria as a
      disruption of narcissism, leading to an apparent relational deadlock. Considering
      hypochondria as a narcissistic transference constitutes a useful contribution of
      psychoanalysis to medicine and psychotherapeutic care. 

PMID- 26290945
TI  - Love at a Distance: Aggression and Hatred in a Schizoid Personality.
AB  - This paper explores the history of aggression as a drive derivative with a
      particular emphasis on understanding the role that it plays in the schizoid
      personality. The author's hypothesis is that schizoid defenses reveal a
      distinction between aggression and what is commonly referred to as "hatred."
      Hatred is a defensive maneuver intended to control aggression. It is not a
      destructive force embedded within it. I propose that the schizoid person defends
      himself or herself by engaging in a sustained seduction away from the aggression
      embedded within love. The schizoid is, in the most defensive expression of
      himself or herself, being seduced by hatred.

PMID- 26290946
TI  - Organic Illness and Psychic Puberty: An Accumulation of Trauma.
AB  - When an adolescent faces serious organic illness, two traumatic events coincide
      and reinforce each other. The Oedipus fantasy and its murderous component are
      exacerbated. Starting psychotherapy in these circumstances is a challenge. Teens
      suffering from serious organic illness rarely request psychological help. They
      accumulate aggressive impulses that remain unspoken but are self-directed. We
      will use excerpts from cases to comment upon the problems and psychical processes
      experienced by such teens. We will show how expressing murder fantasies can be a
      motor in psychotherapy. Such expression not only supports therapy but also
      relieves the patient and contributes to a new psychosomatic equilibrium. 

PMID- 26290947
TI  - On the Path of Election and Martyrdom: Some Psychic Mechanisms Involved in the
      Anders Behring Breivik's Determination as a Terrorist.
AB  - On 22 July 2011, the Norwegian Anders Behring Breivik carried out two attacks in
      Oslo that cost the lives of 77 people, injured many others, and plunged the
      entire Norwegian nation into mourning. When he was arrested, Breivik presented
      himself as a member of the Knights Templar, whose mission is to defend the
      Christian Western world. He considers that he has sacrificed himself by his
      actions for his people and says that he has prepared himself for martyrdom. In
      analysing Breivik's words and writings, this article attempts to identify the
      thought mechanisms involved in Breivik's idea of election (megalomania) and
      martyrology. It highlights the importance of a mechanism of "return to the
      sender," whereby Breivik returns the reproaches directed at him by an agency of
      judgment (ego ideal or superegoic object). It emphasizes the existence of a
      "burning desire" and yearning (Sehnsucht) for this same persecuting superegoic
      object, an object that Breivik constantly wants to find again, even if in death.
      Taking into consideration Searles's hypothesis that the sense of being persecuted
      is a defence against the impossibility of mourning, and also H. Blum's hypothesis
      that persecutory feelings are indicative of fears of a "regressive loss of object
      constancy," the different psychic mechanisms and modes of functioning underlying
      Breivik's terrorist determination are related here to what we know about his
      affective development and infantile relationships.

PMID- 26290951
TI  - Access to Highly Substituted 7-Azaindoles from 2-Fluoropyridines via 7
      Azaindoline Intermediates.
AB  - A versatile synthesis of 7-azaindoles from substituted 2-fluoropyridines is
      described. C3-metalation and 1,4-addition to nitroolefins provide substituted 2
      fluoro-3-(2-nitroethyl)pyridines. A facile oxidative Nef reaction/reductive
      amination/intramolecular SNAr sequence furnishes 7-azaindolines. Finally,
      optional regioselective electrophilic C5-substitution (e.g., bromination or
      nitration) and subsequent in situ oxidation delivers highly functionalized 7
      azaindoles in high overall efficiency. 

PMID- 26290950
TI  - Age-dependent effects of esculetin on mood-related behavior and cognition from
      stressed mice are associated with restoring brain antioxidant status.
AB  - Dietary antioxidants might exert an important role in the aging process by
      relieving oxidative damage, a likely cause of age-associated brain dysfunctions.
      This study aims to investigate the influence of esculetin (6,7
      dihydroxycoumarin), a naturally occurring antioxidant in the diet, on mood
      related behaviors and cognitive function and its relation with age and brain
      oxidative damage. Behavioral tests were employed in 11-, 17- and 22-month-old
      male C57BL/6J mice upon an oral 35day-esculetin treatment (25mg/kg). Activity of
      antioxidant enzymes, GSH and GSSG levels, GSH/GSSG ratio, and mitochondrial
      function were analyzed in brain cortex at the end of treatment in order to assess
      the oxidative status related to mouse behavior. Esculetin treatment attenuated
      the increased immobility time and enhanced the diminished climbing time in the
      forced swim task elicited by acute restraint stress (ARS) in the 11- and 17-month
      old mice versus their counterpart controls. Furthermore, ARS caused an impairment
      of contextual memory in the step-through passive avoidance both in mature adult
      and aged mice which was partially reversed by esculetin only in the 11-month-old
      mice. Esculetin was effective to prevent the ARS-induced oxidative stress mostly
      in mature adult mice by restoring antioxidant enzyme activities, augmenting the
      GSH/GSSG ratio and increasing cytochrome c oxidase (COX) activity in cortex.
      Modulation of the mood-related behavior and cognitive function upon esculetin
      treatment in a mouse model of ARS depends on age and is partly due to the
      enhancement of redox status and levels of COX activity in cortex. 

PMID- 26290952
TI  - Microfluidic Sample Preparation for Medical Diagnostics.
AB  - Fast and reliable diagnoses are invaluable in clinical care. Samples (e.g.,
      blood, urine, and saliva) are collected and analyzed for various biomarkers to
      quickly and sensitively assess disease progression, monitor response to
      treatment, and determine a patient's prognosis. Processing conventional samples
      entails many manual time-consuming steps. Consequently, clinical specimens must
      be processed by skilled technicians before antigens or nucleic acids are
      detected, and these are often present at dilute concentrations. Recently, several
      automated microchip technologies have been developed that potentially offer many
      advantages over traditional bench-top extraction methods. The smaller length
      scales and more refined transport mechanisms that characterize these microfluidic
      devices enable faster and more efficient biomarker enrichment and extraction.
      Additionally, they can be designed to perform multiple tests or experimental
      steps on one integrated, automated platform. This review explores the current
      research on microfluidic methods of sample preparation that are designed to aid
      diagnosis, and covers a broad spectrum of extraction techniques and designs for
      various types of samples and analytes. 

PMID- 26290953
TI  - Comparative analysis of the folding dynamics and kinetics of an engineered
      knotted protein and its variants derived from HP0242 of Helicobacter pylori.
AB  - Understanding the mechanism by which a polypeptide chain thread itself
      spontaneously to attain a knotted conformation has been a major challenge in the
      field of protein folding. HP0242 is a homodimeric protein from Helicobacter
      pylori with intertwined helices to form a unique pseudo-knotted folding topology.
      A tandem HP0242 repeat has been constructed to become the first engineered
      trefoil-knotted protein. Its small size renders it a model system for
      computational analyses to examine its folding and knotting pathways. Here we
      report a multi-parametric study on the folding stability and kinetics of a
      library of HP0242 variants, including the trefoil-knotted tandem HP0242 repeat,
      using far-UV circular dichroism and fluorescence spectroscopy. Equilibrium
      chemical denaturation of HP0242 variants shows the presence of highly populated
      dimeric and structurally heterogeneous folding intermediates. Such equilibrium
      folding intermediates retain significant amount of helical structures except
      those at the N- and C-terminal regions in the native structure. Stopped-flow
      fluorescence measurements of HP0242 variants show that spontaneous refolding into
      knotted structures can be achieved within seconds, which is several orders of
      magnitude faster than previously observed for other knotted proteins.
      Nevertheless, the complex chevron plots indicate that HP0242 variants are prone
      to misfold into kinetic traps, leading to severely rolled-over refolding arms.
      The experimental observations are in general agreement with the previously
      reported molecular dynamics simulations. Based on our results, kinetic folding
      pathways are proposed to qualitatively describe the complex folding processes of
      HP0242 variants. 

PMID- 26290954
TI  - Smartphone Interventions for Weight Treatment and Behavioral Change in Pediatric
      Obesity: A Systematic Review.
AB  - BACKGROUND: Traditional approaches for treating or managing children and
      adolescents with overweight or obesity have limited effectiveness. Current
      advances in smartphone technology may improve the attractiveness and
      accessibility of weight management support for children and adolescents with
      overweight or obesity. This systematic review aimed to provide a comparative
      evaluation of the effectiveness of using smartphones in the multidisciplinary
      treatment of child and adolescent overweight or obesity, with a specific interest
      in behavior change. MATERIALS AND METHODS: The databases of Medline complete,
      OVID, CINAHL, EMBASE, and PubMed were searched for randomized controlled trial
      (RCT) studies addressing behavioral change using smartphone technology, plus
      nutrition and/or physical activity, to treat or manage child and adolescent
      obesity. RESULTS: Only two RCTs have described the effectiveness of smartphone
      devices in pediatric overweight or obesity treatment. Within the limitation of
      the two studies, electronic contact (e-contact) appeared unsuccessful in
      achieving weight loss. However, smartphone usage was linked to improved
      engagement and reduced dropout rates during important sustainability phases of
      these long-term interventions. CONCLUSIONS: Smartphone technologies allow users
      to accomplish tasks anywhere and anytime and, as such, provide researchers with
      additional and generationally appropriate capacities to deliver health promotion.
      E-contact should be used for its significant capacity to prolong engagement and
      decrease withdrawal during sustainability phases that follow intensive
      intervention for weight management in young populations. Despite increasing
      popularity in published protocols of weight management trials, the effectiveness
      of the impact of smartphone technology in pediatric programs remains equivocal.

PMID- 26290956
TI  - Effect of partial-thickness tear on loading capacities of the supraspinatus
      tendon: a finite element analysis.
AB  - Partial-thickness tears of the supraspinatus tendon frequently occur at its
      insertion on the greater tubercule of the humerus, causing pain and reduced
      strength and range of motion. The goal of this work was to quantify the loss of
      loading capacity due to tendon tears at the insertion area. A finite element
      model of the supraspinatus tendon was developed using in vivo magnetic resonance
      images data. The tendon was represented by an anisotropic hyperelastic
      constitutive law identified with experimental measurements. A failure criterion
      was proposed and calibrated with experimental data. A partial-thickness tear was
      gradually increased, starting from the deep articular-sided fibres. For different
      values of tendon tear thickness, the tendon was mechanically loaded up to
      failure. The numerical model predicted a loss in loading capacity of the tendon
      as the tear thickness progressed. Tendon failure was more likely when the tendon
      tear exceeded 20%. The predictions of the model were consistent with experimental
      studies. Partial-thickness tears below 40% tear are sufficiently stable to
      persist physiotherapeutic exercises. Above 60% tear surgery should be considered
      to restore shoulder strength. 

PMID- 26290955
TI  - Improved Phenotype-Based Definition for Identifying Carbapenemase Producers among
      Carbapenem-Resistant Enterobacteriaceae.
AB  - Preventing transmission of carbapenemase-producing, carbapenem-resistant
      Enterobacteriaceae (CP-CRE) is a public health priority. A phenotype-based
      definition that reliably identifies CP-CRE while minimizing misclassification of
      non-CP-CRE could help prevention efforts. To assess possible definitions, we
      evaluated enterobacterial isolates that had been tested and deemed nonsusceptible
      to >1 carbapenem at US Emerging Infections Program sites. We determined the
      number of non-CP isolates that met (false positives) and CP isolates that did not
      meet (false negatives) the Centers for Disease Control and Prevention CRE
      definition in use during our study: 30% (94/312) of CRE had carbapenemase genes,
      and 21% (14/67) of Klebsiella pneumoniae carbapenemase-producing Klebsiella
      isolates had been misclassified as non-CP. A new definition requiring resistance
      to 1 carbapenem rarely missed CP strains, but 55% of results were false positive;
      adding the modified Hodge test to the definition decreased false positives to
      12%. This definition should be considered for use in carbapenemase-producing CRE
      surveillance and prevention. 

PMID- 26290957
TI  - Lessons of synaesthesia for consciousness: Learning from the exception, rather
      than the general.
AB  - The question of whether the mechanisms underlying synaesthesia are similar to
      those ones underlying widespread cases of multisensory interactions tends to
      overshadow the question of whether their manifestations can be thought of as
      being continuous with one another. Here we focus on the conscious manifestations
      of synaesthesia and crossmodal correspondences and consider the dimensions along
      which these could be organised on a continuum. While synaesthesia and crossmodal
      correspondences may differ regarding the degree of vividness, frequency,
      specificity of the conscious manifestation, and control over its content, we
      demonstrate that these dimensions fail to lead to the expected continuous
      distribution. We suggest that the traditional distinction between conscious and
      non-conscious conditions might not be sufficient to separate synaesthesia from
      crossmodal correspondences, but highlight that the conscious manifestations that
      characterize synaesthesia remain exceptional and cannot be reconciled with other
      occasional occurrences of crossmodal mental imagery documented in the case of
      crossmodal correspondences. 

PMID- 26290958
TI  - Protective Effect of Nitric Oxide on Liver Circulation from Ischemia Reperfusion
      Injury.
AB  - INTRODUCTION: The reduction of endogenous nitric oxide (NO) production during
      hepatic ischemia-reperfusion injury, generally via a reduction in endothelial NO
      synthase activity, leads to liver injury. We hypothesized that administration of
      an exogenous NO donor into the portal vein may ameliorate hepatic blood flow
      reduction after a period of ischemia. MATERIAL AND METHODS: A total of 90 min of
      ischemia (portal vein and hepatic artery) was applied in 15 anesthetized pigs,
      using the Pringle method under sevoflurane anesthesia. All animals were
      administered either saline (control group, n = 8) or sodium nitroprusside (SNP, n
      = 7) as exogenous NO donor drugs into the portal vein, 30 min before and after
      ischemia. The portal venous blood flow and hepatic artery blood flow were
      measured continuously using transonic flow probes attached to each vessel.
      Endogenous NO (NOx = NO2- + NO3-) production was measured every 10 min using a
      microdialysis probe placed in the left lobe of the liver. RESULTS: In the SNP
      group, portal venous flow remained unchanged and hepatic artery flow
      significantly increased compared to baseline. Although the production of liver
      tissue NOx transiently decreased to 60% after ischemia, its level in the SNP
      group remained higher than the control saline group. CONCLUSION: Regional
      administration of SNP into the portal vein increases hepatic arterial flow during
      ischemia reperfusion periods without altering mean systemic arterial pressure. We
      speculate that administration of an exogenous NO donor may be effective in
      preventing liver injury via preservation of total hepatic blood flow.

PMID- 26290959
TI  - Chelate Ring Size Effect as a Factor of Selective Fluorescent Recognition of
      Zn(2+) Ions by Pyrrolo[2,3-b]quinoxaline with a Substituted 2-Pyridyl Group
      Receptor.
AB  - Analysis of the spectral properties and structural differences of two turn-on
      ratiometric fluorescent receptors for Zn(2+) and Cd(2+) ions, derivatives of
      pyrrolo[2,3-b]quinoxaline (2), and earlier published 3 (Ostrowska et al.
      CrystEngComm 2015, 17, 498-502) was performed. Both ligands are E/Z push-pull
      olefins interconverting at room temperature, with barriers to rotation about
      enamine double bonds, from E to Z isomers of 19.3 +/- 0.1 and 16.9 +/- 0.3
      kcal/mol and from Z to E of 16.9 +/- 0.3 and 15.7 +/- 0.2 kcal/mol, respectively.
      Diastereoisomers (E)-2 and (Z)-2 were isolated and characterized by X-ray
      structural analysis. The formation of complexes by (E/Z)-2 with acetates and
      acetylacetonates of Zn(2+) and Cd(2+) was monitored by UV-vis, fluorescence, and
      (1)H NMR titrations in acetonitrile, respectively. X-ray structural analysis for
      isolated [(E)-2]2Zn in relation to earlier published (E)-3-ZnOAc revealed the
      formation of a six-coordinated zinc ion with six- and four-membered bis-chelate
      rings by (E)-2. The chelate effect increases the ligand affinity for Zn(2+) (log
      beta12 = 12.45) and causes the elongation of nitrogen-metal bonds. Extension of
      the coordination cavity size allows coordination of a cadmium ion. The
      introduction of a flexible ethylene linker between the fluorophore and ionophore
      pyridyl groups in 3 significantly affects the selectivity of zinc-ion
      recognition. The distorted tetrahedral geometry of (E)-3-ZnOAc with a four
      coordinated zinc ion appears to be the most preferred because of the short donor
      zinc distance with a 1:1 binding mode. The formation of the small coordination
      cavity size with six-membered bis-chelate rings provides an effective overlap of
      zinc and donor orbitals, precluding the coordination of a cadmium ion in the same
      manner as zinc. 

PMID- 26290961
TI  - Progressive endolysosomal deficits impair autophagic clearance beginning at early
      asymptomatic stages in fALS mice.
AB  - Autophagy is an important homeostatic process that functions by eliminating
      defective organelles and aggregated proteins over a neuron's lifetime. One
      pathological hallmark in amyotrophic lateral sclerosis (ALS)-linked motor neurons
      (MNs) is axonal accumulation of autophagic vacuoles (AVs), thus raising a
      fundamental question as to whether reduced autophagic clearance due to an
      impaired lysosomal system contributes to autophagic stress and axonal
      degeneration. We recently revealed progressive lysosomal deficits in spinal MNs
      beginning at early asymptomatic stages in fALS-linked mice expressing the human
      (Hs) SOD1(G93A) protein. Such deficits impair the degradation of AVs engulfing
      damaged mitochondria from distal axons. These early pathological changes are
      attributable to mutant HsSOD1, which interferes with dynein-driven endolysosomal
      trafficking. Elucidation of this pathological mechanism is broadly relevant,
      because autophagy-lysosomal deficits are associated with several major
      neurodegenerative diseases. Therefore, enhancing autophagic clearance by rescuing
      endolysosomal trafficking may be a potential therapeutic strategy for ALS and
      perhaps other neurodegenerative diseases. 

PMID- 26290960
TI  - Equilibrium fluctuation relations for voltage coupling in membrane proteins.
AB  - A general theoretical framework is developed to account for the effects of an
      external potential on the energetics of membrane proteins. The framework is based
      on the free energy relation between two (forward/backward) probability densities,
      which was recently generalized to non-equilibrium processes, culminating in the
      work-fluctuation theorem. Starting from the probability densities of the
      conformational states along the "voltage coupling" reaction coordinate, we
      investigate several interconnected free energy relations between these two
      conformational states, considering voltage activation of ion channels. The free
      energy difference between the two conformational states at zero (depolarization)
      membrane potential (i.e., known as the chemical component of free energy change
      in ion channels) is shown to be equivalent to the free energy difference between
      the two "equilibrium" (resting and activated) conformational states along the one
      dimensional voltage couplin reaction coordinate. Furthermore, the requirement
      that the application of linear response approximation to the free energy
      functionals of voltage coupling should satisfy the general free energy relations,
      yields a novel closed-form expression for the gating charge in terms of other
      basic properties of ion channels. This connection is familiar in statistical
      mechanics, known as the equilibrium fluctuation-response relation. The theory is
      illustrated by considering the coupling of a unit charge to the external voltage
      in the two sites near the surface of membrane, representing the activated and
      resting states. This is done using a coarse-graining (CG) model of membrane
      proteins, which includes the membrane, the electrolytes and the electrodes. The
      CG model yields Marcus-type voltage dependent free energy parabolas for the
      response of the electrostatic environment (electrolytes etc.) to the transition
      from the initial to the final configuratinal states, leading to equilibrium free
      energy difference and free energy barrier that follow the trend of the
      equilibrium fluctuation relation and the Marcus theory of electron transfer.
      These energetics also allow for a direct estimation of the voltage dependence of
      channel activation (Q-V curve), offering a quantitative rationale for a
      correlation between the voltage dependence parabolas and the Q-V curve, upon site
      directed mutagenesis or drug binding. Taken together, by introducing the voltage
      coupling as the energy gap reaction coordinate, our framework brings new
      perspectives to the thermodynamic models of voltage activation in voltage
      sensitive membrane proteins, offering an a framework for a better understating of
      the structure-function correlations of voltage gating in ion channels as well as
      electrogenic phenomena in ion pumps and transporters. Significantly, this
      formulation also provides a powerful bridge between the CG model of voltage
      coupling and the conventional macroscopic treatments. 

PMID- 26290962
TI  - Synthesis of hierarchical porous delta-MnO2 nanoboxes as an efficient catalyst
      for rechargeable Li-O2 batteries.
AB  - A rechargeable lithium-oxygen (Li-O2) battery with a remarkably high theoretical
      energy storage capacity has attracted enormous research attention. However, the
      poor oxygen reduction and oxygen evolution reaction (ORR and OER) activities in
      discharge and charge processes cause low energy efficiency, poor electrolyte
      stability and short cycle life. This requires the development of efficient
      cathode catalysts to dramatically improve the Li-O2 battery performances. MnO2
      based materials are recognized as efficient and low-cost catalysts for a Li-O2
      battery cathode. Here, we report a controllable approach to synthesize
      hierarchical porous delta-MnO2 nanoboxes by using Prussian blue analogues as the
      precursors. The obtained products possess hierarchical pore size and an extremely
      large surface area (249.3 m(2) g(-1)), which would favour oxygen transportation
      and provide more catalytically active sites to promote ORR and OER as the Li-O2
      battery cathode. The battery shows enhanced discharge capacity (4368 mA h g(
      1)@0.08 mA cm(-2)), reduced overpotential (270 mV), improved rate performance and
      excellent cycle stability (248 cycles@500 mA h g(-1) and 112 cycles@1000 mA h g(
      1)), in comparison with the battery with a VX-72 carbon cathode. The superb
      performance of the hierarchical porous delta-MnO2 nanoboxes, together with a
      convenient fabrication method, presents an alternative to develop advanced
      cathode catalysts for the Li-O2 battery. 

PMID- 26290963
TI  - NOx Reactions on Aqueous Surfaces with Gaseous HCl: Formation of a Potential
      Precursor to Atmospheric Cl Atoms.
AB  - Chlorine atoms are highly reactive free radicals known to catalyze ozone
      depletion in the stratosphere and organic oxidation in the troposphere. They are
      readily produced photolytically upon irradiation of some stable Cl containing
      species, for instance, nitrosyl chloride, ClNO. We predict the formation of ClNO
      using ab initio molecular dynamics (AIMD) simulations of an NO2 dimer on the
      surface of a thin film of water upon which gaseous HCl impinges. The reactant is
      chloride ion formed when HCl ionizes on the water film. The same mechanism for
      ClNO production may occur in humid environments when ONONO2 (the asymmetric NO2
      dimer examined here) comes in contact with either HCl or sea salt. The film of
      water serves to (1) stabilize ONONO2 on the film surface so that it is localized
      and physically accessible for reaction, (2) provide the medium to ionize HCl, and
      (3) activate ONONO2 making it more susceptible to nucleophilic attack by
      chloride. This substitution/elimination mechanism is new for NOx chemistry on
      thin water films and could not be derived from studies on small clusters. 

PMID- 26290964
TI  - Aqueous Redox Chemistry and the Electronic Band Structure of Liquid Water.
AB  - The electronic states of aqueous species can mix with the extended states of the
      solvent if they are close in energy to the band edges of water. Using density
      functional theory-based molecular dynamics simulation, we show that this is the
      case for OH(-) and Cl(-). The effect is, however, badly exaggerated by the
      generalized gradient approximation leading to systematic underestimation of redox
      potentials and spurious nonlinearity in the solvent reorganization. Drawing a
      parallel to charged defects in wide gap solid oxides, we conclude that
      misalignment of the valence band of water is the main source of error turning the
      redox levels of OH(-) and Cl(-) in resonant impurity states. On the other hand,
      the accuracy of energies of levels corresponding to strongly negative redox
      potentials is acceptable. We therefore predict that mixing of the vertical
      attachment level of CO2 and the unoccupied states of water is a real effect. 

PMID- 26290966
TI  - Two Isomers of Protonated Isocyanic Acid: Evidence for an Ion-Molecule Pathway
      for HNCO <-> HOCN Isomerization.
AB  - Ion-molecule reactions are thought to play a crucial role in the formation of
      metastable isomers, but relatively few protonated intermediates beyond HNCH(+)
      have been characterized at high spectral resolution. We present here laboratory
      measurements of the rotational spectra of protonated isocyanic acid in two
      isomeric forms, the ground state H2NCO(+) with C2v symmetry and a low-lying bent
      chain HNCOH(+), guided by coupled cluster calculations of their molecular
      structure. Somewhat surprisingly, HNCOH(+) is found to be more abundant than
      H2NCO(+), even though this metastable isomer is calculated to lie approximately
      15-20 kcal/mol higher in energy. In the same way that HCNH(+) serves as a key
      intermediate in ion-molecule reactions that form HNC via dissociative electron
      recombination in cold dense interstellar molecular clouds, HNCOH(+) may play an
      analogous role in the conversion of HNCO to HOCN. 

PMID- 26290965
TI  - Theoretical Study of the Validity of the Polanyi Rules for the Late-Barrier Cl +
      CHD3 Reaction.
AB  - The Polanyi rules, which state that vibrational energy is more efficient in
      promoting a late-barrier reaction than translational energy, were questioned
      recently by an experimental unexpected finding that the CH stretch excitation is
      no more effective in promoting the late-barrier Cl + CHD3 reaction than the
      translational energy. However, the present quantum dynamics study on the best
      available potential energy surface for the title reaction reveals that the CH
      stretch excitation does promote the reaction significantly, except at low
      collision energies. Further studies should be carried out to solve the
      disagreements between theory and experiment on the reaction. 

PMID- 26290967
TI  - Adsorption Geometry of CO versus Coverage on TiO2(110) from s- and p-Polarized
      Infrared Spectroscopy.
AB  - The adsorption of CO on reduced, rutile TiO2(110) is investigated using IR
      reflection-absorption spectroscopy and temperature-programmed desorption.
      Experiments using s- and p-polarized IR light incident along the [001] and [110]
      azimuths give detailed information on the adsorption geometry of the CO as a
      function of the CO coverage, thetaCO. The results indicate that for thetaCO <= 1
      ML, CO adsorbs oriented perpendicular to the surface at Ti5c sites. For 1 <
      thetaCO <= 1.5 ML, the bonding geometry of the CO adsorbed at Ti5c sites is
      unchanged, whereas the additional CO molecules adsorb at Ob sites parallel to the
      surface and parallel to the [110] azimuth. The results do not support previous
      suggestions that CO at Ti5c sites tilt ~20 degrees  from normal at high
      coverages. The results demonstrate the utility of polarization-resolved infrared
      reflection-absorption spectroscopy for elucidating adsorption geometries on
      dielectric substrates. 

PMID- 26290968
TI  - Spin Crossover in a Vacuum-Deposited Submonolayer of a Molecular Iron(II)
      Complex.
AB  - Spin-state switching of transition-metal complexes (spin crossover) is sensitive
      to a variety of tiny perturbations. It is often found to be suppressed for
      molecules directly adsorbed on solid surfaces. We present X-ray absorption
      spectroscopy measurements of a submonolayer of [Fe(II)(NCS)2L] (L: 1-{6-[1,1
      di(pyridin-2-yl)ethyl]-pyridin-2-yl}-N,N-dimethylmethanamine) deposited on a
      highly oriented pyrolytic graphite substrate in ultrahigh vacuum. These molecules
      undergo a thermally induced, fully reversible, gradual spin crossover with a
      transition temperature of T1/2 = 235(6) K and a transition width of DeltaT80 =
      115(8) K. Our results show that by using a carbon-based substrate the spin
      crossover behavior can be preserved even for molecules that are in direct contact
      with a solid surface. 

PMID- 26290969
TI  - Vapors from Ionic Liquids: Reconciling Simulations with Mass Spectrometric Data.
AB  - The species involved in the distillation of aprotic ionic liquids are discussed
      in light of recent simulations and mass spectrometric data obtained by various
      techniques. New mass spectrometric data collected via laser-induced acoustic
      desorption and the thermal desorption of ionic liquids are also presented as well
      as additional DFT calculations. The available evidence of theoretical simulations
      and mass spectrometric data suggests that the distillation of ionic liquids
      occurs mainly via neutral ion pairs of composition CnAn [C(+) = cation and A(-) =
      anion], followed by gas-phase dissociation to lower order ion pairs and then
      dissociation of hot CA to C(+) and A(-), followed by ion/molecule association
      events to give [CnAn-1](+) or [Cn-1An](-) ions to a degree that depends on the
      amount of internal energy deposited into the neutral CnAn clusters upon
      evaporation. 

PMID- 26290970
TI  - Layer-by-Layer Quantum Dot Assemblies for the Enhanced Energy Transfers and Their
      Applications toward Efficient Solar Cells.
AB  - Two different quantum dots (QDs) with an identical optical band gap were
      prepared: one without the inorganic shell and short surface ligands (BQD) and the
      other with thick inorganic shells and long surface ligands (OQD). They were
      surface-derivatized to be positively or negatively charged and were used for
      layer-by-layer assemblies on TiO2. By sandwiching BQD between OQD and TiO2, OQD
      photoluminescence showed seven times faster decay, which is attributed to the
      combined effect of the efficient energy transfer from OQD to BQD with the FRET
      efficiency of 86% and fast electron transfer from BQD to TiO2 with the rate of
      1.2 * 10(9) s(-1). The QD bilayer configuration was further applied to solar
      cells, and showed 3.6 times larger photocurrent and 3.8 times larger
      photoconversion efficiency than those of the device with the OQD being sandwiched
      by BQD and TiO2. This showcases the importance of sophisticated control of QD
      layer assembly for the design of efficient QD solar cells. 

PMID- 26290971
TI  - Dissecting Local Atomic and Intermolecular Interactions of Transition-Metal Ions
      in Solution with Selective X-ray Spectroscopy.
AB  - Determining covalent and charge-transfer contributions to bonding in solution has
      remained an experimental challenge. Here, the quenching of fluorescence decay
      channels as expressed in dips in the L-edge X-ray spectra of solvated 3d
      transition-metal ions and complexes was reported as a probe. With a full set of
      experimental and theoretical ab initio L-edge X-ray spectra of aqueous Cr(3+),
      including resonant inelastic X-ray scattering, we address covalency and charge
      transfer for this prototypical transition-metal ion in solution. We dissect local
      atomic effects from intermolecular interactions and quantify X-ray optical
      effects. We find no evidence for the asserted ultrafast charge transfer to the
      solvent and show that the dips are readily explained by X-ray optical effects and
      local atomic state dependence of the fluorescence yield. Instead, we find,
      besides ionic interactions, a covalent contribution to the bonding in the aqueous
      complex of ligand-to-metal charge-transfer character. 

PMID- 26290972
TI  - Rediscovering the Wheel. Thermochemical Analysis of Energetics of the Aromatic
      Diazines.

PMID- 26290973
TI  - Computational Insights into Dynamics of Protein Aggregation and Enzyme-Substrate
      Interactions.
AB  - In this Perspective, the roles of protein dynamics have been discussed in the
      aggregation of amyloid beta (Abeta) peptides and formation of enzyme-substrate
      complexes of beta-secretase (BACE1) and insulin-degrading enzyme (IDE). The
      studies regarding the influence of individual amino acid residues and specific
      regions on the structures and oligomerization of early Abeta aggregates and
      computations of their translational and rotational diffusion coefficients and
      order parameters exhibited that even the short-time-scale molecular dynamics
      simulations can reproduce certain experimental parameters with reasonable
      accuracy. The simulations elucidating the enzyme-substrate interactions of BACE1
      and IDE successfully showed that the chemical nature and length of the substrates
      influence the dynamics and plasticity of both the enzyme and substrate. An atomic
      level understanding of these processes will advance our efforts to develop
      therapeutic strategies for several deadly diseases through the design of small
      molecules with antiaggregation properties and substrate-specific "designer" forms
      of enzymes. 

PMID- 26290974
TI  - Understanding the Thickness-Dependent Performance of Organic Bulk Heterojunction
      Solar Cells: The Influence of Mobility, Lifetime, and Space Charge.
AB  - We investigate the reasons for the dependence of photovoltaic performance on the
      absorber thickness of organic solar cells using experiments and drift-diffusion
      simulations. The main trend in photocurrent and fill factor versus thickness is
      determined by mobility and lifetime of the charge carriers. In addition, space
      charge becomes more and more important the thicker the device is because it
      creates field free regions with low collection efficiency. The two main sources
      of space-charge effects are doping and asymmetric mobilities. We show that for
      our experimental results on Si-PCPDTBT:PC71BM (poly[(4,40-bis(2
      ethylhexyl)dithieno[3,2-b:20,30-d]silole)-2,6-diyl-alt-(4,7-bis(2-thienyl)-2,1,3
      benzothiadiazole)-5,50-diyl]:[6,6]-phenyl C71-butyric acid methyl ester) solar
      cells, the influence of doping is most likely the dominant influence on the space
      charge and has an important effect on the thickness dependence of performance. 

PMID- 26290975
TI  - Ligand Diffusion on Protein Surface Observed in Molecular Dynamics Simulation.
AB  - The process of binding of small ligands to dihydrofolate reductase protein has
      been investigated using all-atom molecular dynamics simulations. The existence of
      a mechanism that facilitates the search of the binding site by the ligand is
      demonstrated. The mechanism consists of ligand diffusing on the protein's
      surface. It has been discussed in the literature before, but has not been
      explicitly confirmed for realistic molecular systems. The strength of this
      nonspecific binding is roughly estimated and found to be essential for the
      binding kinetics. 

PMID- 26290976
TI  - Platinum Monolayer Electrocatalysts for Anodic Oxidation of Alcohols.
AB  - The slow, incomplete oxidation of methanol and ethanol on platinum-based anodes
      as well as the high price and limited reserves of Pt has hampered the practical
      application of direct alcohol fuel cells. We describe the electrocatalysts
      consisting of one Pt monolayer (one atom thick layer) placed on extended or
      nanoparticle surfaces having the activity and selectivity for the oxidation of
      alcohol molecules that can be controlled with platinum-support interaction. The
      suitably expanded Pt monolayer (i.e., Pt/Au(111)) exhibits a factor of 7 activity
      increase in catalyzing methanol electrooxidation relative to Pt(111). Sizable
      enhancement is also observed for ethanol electrooxidation. Furthermore, a
      correlation between substrate-induced lateral strain in a Pt monolayer and its
      activity/selectivity is established and rationalized by experimental and
      theoretical studies. The knowledge we gained with single-crystal model catalysts
      was successfully applied in designing real nanocatalysts. These findings for
      alcohols are likely to be applicable for the oxidation of other classes of
      organic molecules. 

PMID- 26290977
TI  - Optimized Vertical Carbon Nanotube Forests for Multiplex Surface-Enhanced Raman
      Scattering Detection.
AB  - The highly sensitive and molecule-specific technique of surface-enhanced Raman
      spectroscopy (SERS) generates high signal enhancements via localized optical
      fields on nanoscale metallic materials, which can be tuned by manipulation of the
      surface roughness and architecture on the submicrometer level. We investigate
      gold-functionalized vertically aligned carbon nanotube forests (VACNTs) as low
      cost straightforward SERS nanoplatforms. We find that their SERS enhancements
      depend on their diameter and density, which are systematically optimized for
      their performance. Modeling of the VACNT-based SERS substrates confirms
      consistent dependence on structural parameters as observed experimentally. The
      created nanostructures span over large substrate areas, are readily configurable,
      and yield uniform and reproducible SERS enhancement factors. Further fabricated
      micropatterned VACNTs platforms are shown to deliver multiplexed SERS detection.
      The unique properties of CNTs, which can be synergistically utilized in VACNT
      based substrates and patterned arrays, can thus provide new generation platforms
      for SERS detection. 

PMID- 26290978
TI  - Relative Phase Change of Nearby Resonances in Temporally Delayed Sum Frequency
      Spectra.
AB  - Surface-selective sum frequency generation (SFG) spectroscopy has been previously
      shown to benefit from a finite time delay between two input laser pulses, which
      suppresses the nonresonant background and improves spectral resolution. Here we
      demonstrate another consequence of the time delay in SFG: depending on the
      magnitude of the delay, nearby resonances (e.g., vibrational modes) can "flip"
      their relative phase, i.e., appear either in-phase or out-of-phase with one
      another, resulting in either constructive or destructive interference in SFG
      spectra. This is significant for interpretation of the SFG spectra, in particular
      because the sign of the resonant amplitude provides the absolute molecular
      orientation (up vs down) of the vibrational chromophore. We present results and
      model calculations for symmetric and asymmetric CH-stretch modes of the methyl
      terminated Si(111) surface, showing that the phase flip occurs when the delay
      matches half-cycle of the difference frequency between the two modes. 

PMID- 26290979
TI  - Local Lipid Reorganization by a Transmembrane Protein Domain.
AB  - Membrane proteins interact with their lipid bilayer environment via both a
      transmembrane helix and juxtamembrane regions. The effect of juxtamembrane
      regions and membrane lipid composition on these interactions has been explored by
      multiscale molecular dynamics simulations. The consequences of anionic lipids
      within the inner leaflet of a membrane were studied in combination with membrane
      spanning protein models differing in their juxtamembrane domains. The simulations
      reveal sensitivity of the protein-lipid interactions to membrane lipid
      composition and charged amino acid side chains. Basic residues on the
      intracellular side of the protein facilitated interactions with anionic lipids.
      Protein systems without basic residues do not show selectivity for anionic
      compared with zwitterionic lipids. This reveals the sensitivity to the
      composition of both the membrane and the protein system when studying membrane
      embedded proteins. The results presented here illustrate how even a simple
      transmembrane domain is able to induce lipid reorganization in a mixed asymmetric
      bilayer. 

PMID- 26290980
TI  - Probing Electronic Doping of Single-Walled Carbon Nanotubes by Gaseous Ammonia
      with Dielectric Force Microscopy.
AB  - The electronic properties of single-walled carbon nanotubes (SWNTs) are sensitive
      to the gas molecules adsorbed on nanotube sidewalls. It is imperative to
      investigate the interaction between SWNTs and gas molecules in order to
      understand the mechanism of SWNT-based gas-sensing devices or the stability of
      individual SWNT-based field effect transistors (FETs). To avoid the Schottky
      barrier at the metal/SWNT contact, which dominates the performance of SWNT-based
      FETs, we utilize a contactless technique, dielectric force microscopy (DFM), to
      study the intrinsic interaction between SWNTs and gaseous ammonia molecules.
      Results show that gaseous ammonia affects the conductivity of semiconducting
      SWNTs but not metallic SWNTs. Semiconducting SWNTs, which are p-type doped in
      air, show suppressed hole concentration in ammonia gas and are even inverted to n
      type doping in some cases. 

PMID- 26290981
TI  - Molecular-Level Insight into the Spectral Tuning Mechanism of the DsRed
      Chromophore.
AB  - We present a detailed study of the protein environmental effects on the one- and
      two-photon absorption (1PA and 2PA, respectively) properties of the S0-S1
      transition in the DsRed protein using the polarizable embedding density
      functional theory formalism. We find that steric factors and chromophore-protein
      interactions act in concert to enhance the 2PA activity inside the protein while
      adversely blue-shifting the 1PA maximum. A two-state model reveals that the 2PA
      intensity gain is primarily governed by the increased change in the permanent
      dipole moment between the ground and the excited states acquired inside the
      protein. Our results indicate that this mainly is attributable to counter
      directional contributions stemming from Lys163 and the conserved Arg95 with the
      former additionally identified as a key residue in the color tuning mechanism.
      The results provide new insight into the tuning mechanism of DsRed and suggest a
      possible strategy for simultaneous improvement of its 1PA and 2PA properties. 

PMID- 26290982
TI  - Phototautomerization of Acetaldehyde to Vinyl Alcohol: A Primary Process in UV
      Irradiated Acetaldehyde from 295 to 335 nm.
AB  - The concentrations of organic acids, key species in the formation of secondary
      organic aerosols, are underestimated by atmospheric chemistry models by a factor
      of ~2. Vinyl alcohol (VA, CH2?CHOH, ethenol) has been suggested as a precursor to
      formic acid, but sufficient tropospheric sources of VA have not been identified.
      Here, we show that VA is formed upon irradiation of neat acetaldehyde (CH3CHO) in
      the actinic ultraviolet region, between 295 and 330 nm. Besides the well-known
      photochemical products CO and CH4, we infer up to a 15% quantum yield of VA at 20
      Torr acetaldehyde pressure and a photolysis wavelength of 330 nm. The experiments
      confirm a recent model predicting phototautomerization of acetaldehyde to VA and
      imply that photolysis of small aldehydes and ketones could provide tropospheric
      sources of enols sufficient to impact organic acid budgets. We also report
      absolute infrared absorption cross sections of VA. 

PMID- 26290983
TI  - Different Methods of Increasing the Mechanical Strength of Gold Nanocages.
AB  - Using the ultrafast coherent modulation of the surface plasmon band intensity
      with the totally symmetric lattice vibration of gold nanocages, we were able to
      determine and use their frequencies as a measure of the cage's mechanical
      stability. The presence of an inner "stiff" transition-metal nanoshell with a
      higher value of the elastic modulus is found to increase the frequency of the
      lattice vibration of the outer soft gold nanoshell. This could also explain the
      observed increase in both the gold lattice vibrational frequency as well as the
      lattice vibration relaxation time in the Au-Pt and Au-Pd double-shell nanocages.
      It is also found that when these nanoparticles are assembled into monolayers on
      quartz substrates by the Langmuir-Blodgett technique, the oscillation frequency
      of the gold shell with the transition metal having the largest elastic constant
      suffers the least change in its oscillation frequency as a result of its
      resistance to distortion as a result of binding to the substrate. 

PMID- 26290984
TI  - In Vitro Enzyme Comparative Kinetics: Unwinding of Surface-Bound DNA
      Nanostructures by RecQ and RecQ1.
AB  - Many cellular processes entail the separation of nucleic acid strands. Helicases
      are involved in the separation of the double-stranded DNA, a process fueled by
      ATP hydrolysis. We investigated the reaction mechanism of two homologous
      helicases, the bacterial RecQ and the human RECQ1, in vitro, that is, within
      confined DNA monolayers. We generate arrays of engineered DNA sequences by atomic
      force microscopy (AFM) nanografting and monitor the enzyme activity on the
      surface by means of differential, highly precise AFM measurements of the DNA
      height variation. The latter is associated with the unwinding action of the
      enzyme onto the surface-bound DNAs because it arises from the different
      mechanical properties of single- versus double-stranded DNA that are sensibly
      detected by AFM. Our results highlight different kinetic behaviors for these
      enzymes under the same experimental conditions. 

PMID- 26290985
TI  - Circular Dichroism Measured on Single Chlorosomal Light-Harvesting Complexes of
      Green Photosynthetic Bacteria.
AB  - We report results on circular dichroism (CD) measured on single immobilized
      chlorosomes of a triple mutant of green sulfur bacterium Chlorobaculum tepidum .
      The CD signal is measured by monitoring chlorosomal bacteriochlorphyll c
      fluorescence excited by alternate left and right circularly polarized laser light
      with a fixed wavelength of 733 nm. The excitation wavelength is close to a
      maximum of the negative CD signal of a bulk solution of the same chlorosomes. The
      average CD dissymmetry parameter obtained from an ensemble of individual
      chlorosomes was gs = -0.025, with an intrinsic standard deviation (due to
      variations between individual chlorosomes) of 0.006. The dissymmetry value is
      about 2.5 times larger than that obtained at the same wavelength in the bulk
      solution. The difference can be satisfactorily explained by taking into account
      the orientation factor in the single-chlorosome experiments. The observed
      distribution of the dissymmetry parameter reflects the well-ordered nature of the
      mutant chlorosomes. 

PMID- 26290986
TI  - Time-Temperature Scaling of Conductivity Spectra of Organic Plastic Crystalline
      Conductors.
AB  - Organic plastic crystalline soft matter ion conductors are interesting
      alternatives to liquid electrolytes in electrochemical storage devices such as
      lithium-ion batteries. The solvent dynamics plays a major role in determining the
      ion transport in plastic crystalline ion conductors. We present here an analysis
      of the frequency-dependent ionic conductivity of succinonitrile-based plastic
      crystalline ion conductors at varying salt composition (0.005 to 1 M) and
      temperature (-20 to 60  degrees C) using time-temperature superposition principle
      (TTSP). The main motivation of the work has been to establish comprehensive
      insight into the ion transport mechanism from a single method viz. impedance
      spectroscopy rather than employing cluster of different characterization methods
      probing various length and time scales. The TTSP remarkably aids in explicit
      identification of the extent of the roles of solvent dynamics and ion-ion
      interactions on the effective conductivity of the orientationally disordered
      plastic crystalline ion conductors. 

PMID- 26290987
TI  - Chemical Preinsertion of Lithium: An Approach to Improve the Intrinsic Capacity
      Retention of Bulk Si Anodes for Li-ion Batteries.
AB  - Silicon represents one of the most promising anodes for next-generation Li-ion
      batteries due to its very high capacity and low electrochemical potential.
      However, the extremely poor cycling stability caused by the huge volume change
      during charge/discharge prevents it from the commercial use. In this work, we
      propose a strategy to decrease the intrinsic volume change of bulk Si-based
      anodes by preinsertion Li into Si with a chemical reaction. Amorphous Li12Si7 was
      successfully synthesized by a hydrogen-driven reaction between LiH and Si
      associated with subsequent energetic ball milling. The as-prepared amorphous
      Li12Si7 anode exhibits significantly improved lithium storage ability as ~70.7%
      of the initial charge capacity is retained after 20 cycles. This finding opens up
      the possibility to develop bulk Si-based anodes with high capacity, long cycling
      life and low fabrication cost for Li-ion batteries. 

PMID- 26290988
TI  - Enrichment of Paramagnetic Ions from Homogeneous Solutions in Inhomogeneous
      Magnetic Fields.
AB  - Applying interferometry to an aqueous solution of paramagnetic manganese ions,
      subjected to an inhomogeneous magnetic field, we observe an unexpected but highly
      reproducible change in the refractive index. This change occurs in the top layer
      of the solution, closest to the magnet. The shape of the layer is in accord with
      the spatial distribution of the largest component of the magnetic field gradient
      force. It turns out that this layer is heavier than the underlying solution
      because it undergoes a Rayleigh-Taylor instability upon removal of the magnet.
      The very good agreement between the magnitudes of buoyancy, associated with this
      layer, and the field gradient force at steady state provides conclusive evidence
      that the layer formation results from an enrichment of paramagnetic manganese
      ions in regions of high magnetic field gradient. 

PMID- 26290989
TI  - Ab Initio Calculations of X-ray Spectra: Atomic Multiplet and Molecular Orbital
      Effects in a Multiconfigurational SCF Approach to the L-Edge Spectra of
      Transition Metal Complexes.
AB  - A new ab initio approach to the calculation of X-ray spectra is demonstrated. It
      combines a high-level quantum chemical description of the chemical interactions
      and local atomic multiplet effects. We show here calculated L-edge X-ray
      absorption (XA) and resonant inelastic X-ray scattering spectra for aqueous
      Ni(2+) and XA spectra for a polypyridyl iron complex. Our quantum chemical
      calculations on a high level of accuracy in a post-Hartree-Fock framework give
      excellent agreement with experiment. This opens the door to reliable and detailed
      information on chemical interactions and the valence electronic structure in 3d
      transition-metal complexes also in transient excited electronic states. As we
      combine a molecular-orbital description with a proper treatment of local atomic
      electron correlation effects, our calculations uniquely allow, in particular,
      identifying the influence of interatomic chemical interactions versus intra
      atomic correlations in the L-edge X-ray spectra. 

PMID- 26290990
TI  - Hydrogen-Bond Network Transformation in Water-Cluster Anions Induced by the
      Complex Formation with Benzene.
AB  - We report spectroscopic evidence of isomer interconversion in water cluster
      anions, (H2O)n(-), which occurs through the interaction with a benzene molecule.
      An anion complex composed of (H2O)6(-) and benzene, Bz.(H2O)6(-), is formed via
      the reaction of (H2O)6(-)Arm with benzene. The reaction proceeds as an Ar
      mediated association process such that a rapid energy dissipation by sequential
      Ar evaporation efficiently suppresses the thermionic emission of e(-), H2O, or
      both, giving rise to the formation of Bz.(H2O)6(-). Photoelectron spectroscopy is
      employed to probe the electronic properties of the anionic species, which reveals
      that "type I -> type II" isomer interconversion proceeds in the (H2O)6(-) moiety
      during the formation of Bz.(H2O)6(-). With the aid of ab initio calculations, we
      conclude that the interconversion is driven by preferential stabilization of the
      H-bond network of type II arrangement through the formation of a nonconventional
      O-H...pi hydrogen bond between (H2O)6(-) and Bz. 

PMID- 26290991
TI  - The Adiabatic Ionization Energy and Triplet T1 Energy of Jet-Cooled Keto-Amino
      Cytosine.
AB  - Gas-phase cytosine exists in five different tautomer/rotamer forms 1, 2a, 2b, 3a,
      and 3b. We determine the threshold ionization energy (IE) of the keto-amino
      tautomer 1 as 8.73 +/- 0.02 eV, using resonant two-photon ionization mass
      spectrometry in a supersonic molecular beam via the (1)pipi* excited state. This
      is the first IE threshold measurement for the biologically relevant tautomer 1.
      The IE of the thermal gas-phase mixture of cytosine has been measured as 8.60 +/-
      0.05 eV by Kostko et al. using single-photon VUV photoionization [Phys. Chem.
      Chem. Phys., 2010, 12, 2860]. Given the tautomer distribution and ionization
      energies calculated in that work, our determination of the keto-amino tautomer IE
      implies that the IE measured by Kostko et al. is dominated by the enol-amino
      tautomers 2a and 2b. Upon excitation of keto-amino cytosine to its (1)pipi*
      state, relaxation occurs to a lower-lying long-lived state. The IE threshold
      measured via this state places its energy about 0.69 eV below the (1)pipi* state,
      in good agreement with the triplet T1 energy of keto-amino cytosine calculated by
      several high-level ab initio methods. The identification of keto-amino cytosine
      T1 is the basis for characterizing the intersystem crossing rates into and the
      photochemical reactions of this long-lived state. 

PMID- 26290992
TI  - Redox Reaction Mechanisms with Non-triiodide Mediators in Dye-Sensitized Solar
      Cells by Redox Potential Calculations.
AB  - We investigate reaction mechanisms of the redox mediators in dye-sensitized solar
      cells through systematic calculations of redox potentials of possible cobalt
      complexes and iodides in acetonitrile solution by use of the thermodynamic cycle
      method with continuum solvent model. The calculated redox potentials were in good
      agreement with the experimental values, although the experimentalists used
      different reference electrodes. The maximum open circuit voltage (VOC) of the
      mediators calculated in this work indicate that the I2(*-)/2I(-) and I2/I2(*-) as
      well as the net I2/2I(-) redox reactions can dominate at both photoanode and
      counter-electrode. 

PMID- 26290993
TI  - Attenuating Away the Errors in Inter- and Intramolecular Interactions from Second
      Order Moller-Plesset Calculations in the Small Aug-cc-pVDZ Basis Set.
AB  - Second-order Moller-Plesset perturbation theory (MP2) treats electron correlation
      at low computational cost, but suffers from basis set superposition error (BSSE)
      and fundamental inaccuracies in long-range contributions. The cost differential
      between complete basis set (CBS) and small basis MP2 restricts system sizes where
      BSSE can be removed. Range-separation of MP2 could yield more tractable and/or
      accurate forms for short- and long-range correlation. Retaining only short-range
      contributions proves to be effective for MP2 in the small aug-cc-pVDZ (aDZ)
      basis. Using one range-separation parameter, superior behavior is obtained versus
      both MP2/aDZ and MP2/CBS for inter- and intramolecular test sets. Attenuation of
      the long-range helps to cancel both BSSE and intrinsic MP2 errors. Direct scaling
      of the MP2 correlation energy proves useful as well. The resulting SMP2/aDZ,
      MP2(erfc, aDZ), and MP2(terfc, aDZ) methods perform far better than MP2/aDZ
      across systems with hydrogen-bonding, dispersion, and mixed interactions at a
      fraction of MP2/CBS computational cost. 

PMID- 26290994
TI  - BaTiO3 Nanotubes-Based Flexible and Transparent Nanogenerators.
AB  - We have developed a simple, cost-effective, and scalable approach to fabricate a
      piezoelectric nanogenerator (NG) with stretchable and flexible characteristics
      using BaTiO3 nanotubes, which were synthesized by the hydrothermal method. The NG
      was fabricated by making a composite of the nanotubes with polymer
      poly(dimethylsiloxane) (PDMS). The peak open-circuit voltage and short-circuit
      current of the NG reached a high level of 5.5 V and 350 nA (current density of
      350 nA/cm(2)), respectively. It was used to directly drive a commercial liquid
      crystal display. The BaTiO3 nanotubes/PDMS composite is highly transparent and
      useful for a large-scale (11 * 11 cm) fabrication of lead-free piezoelectric NG. 

PMID- 26290995
TI  - Toggling Between Blue- and Red-Emitting Fluorescent Silver Nanoclusters.
AB  - A very efficient protocol for synthesizing highly fluorescent, protein-templated
      silver nanoclusters (Ag/NCs) has been discussed. Two types of Ag/NCs (Ag9/HSA and
      Ag14/HSA), although showing significant differences in their photophysical
      properties, can be interconverted at will, which makes this study unique. The
      Ag/HSA NCs have been quantified by several spectroscopic techniques, and they
      find tremendous applications as photoluminescent markers. Besides their rather
      easy synthetic methodology, our Ag/HSA NCs show two-photon excitation properties
      that enable them to be used in bioimaging. 

PMID- 26290996
TI  - Excitation Energy Transfer and Low-Efficiency Photolytic Splitting of Water Ice
      by Vacuum UV Light.
AB  - Experimental estimates of photolytic efficiency (yield per photon) for
      photodissociation and photodesorption from water ice range from about 10(-3) to
      10(-1). However, in the case of photodissociation of water in the gas phase, it
      is close to unity. Exciton dynamics carried out by a quantum mechanical time
      dependent propagator shows that in the eight most stable water hexamers, the
      excitation diffuses away from the initially excited molecule within a few
      femtoseconds. On the basis of these quantum dynamics simulations, it is
      hypothesized that the ultrafast exciton energy transfer process, which in general
      gives rise to a delocalized exciton within these clusters, may contribute to the
      low efficiency of photolytic processes in water ice. It is proposed that exciton
      diffusion inherently competes with the nuclear dynamics that drives the
      photodissociation process in the repulsive S1 state on the sub-10 fs time scale. 

PMID- 26290997
TI  - Surface Plasmon-Coupled Emission of Rhodamine 110 Aggregates in a Silica
      Nanolayer.
AB  - First analysis of strong directional surface plasmon-coupled emission (SPCE) of
      ground-state formed intermolecular aggregates of Rhodamine 110 (R110) in silica
      nanofilms deposited on silver nanolayers is reported. Until now, the processes of
      energy transport and its trapping due to aggregate formation have not been
      studied in the presence of SPCE. A new approach to multicomponent systems with
      weakly and strongly fluorescent centers making use of fluorophore-surface plasmon
      interaction is presented. The analysis is based on comparison of experimental
      free-space emission spectra (F-SE), experimental SPCE with theoretical surface
      plasmon resonance spectra (SPR). It is shown that, due to the dispersion of SPCE,
      the detection of weak aggregate emission is straightforward if only the monomers
      and aggregates fluorescence spectra are somewhat spectrally shifted. SPCE studies
      confirmed the formation of weakly fluorescent higher order aggregates of R110 in
      silica films. The results indicate that the increase of energy transfer from
      monomers to aggregates is due to fluorophore-plasmon interaction. 

PMID- 26290998
TI  - Diffusion Length in Nanoporous Photoelectrodes of Dye-Sensitized Solar Cells
      under Operating Conditions Measured by Photocurrent Microscopy.
AB  - We determined the carrier diffusion lengths in nanoporous layers of dye
      sensitized solar cells by using scanning photocurrent microscopy. The diffusion
      lengths were found to be 60-100 MUm for the conventional cells. In addition, we
      found a correlation between the carrier diffusion lengths and the cell
      efficiency, which proved that improvement in the diffusion length is one of the
      crucial factors for optimizing device performance. The diffusion length was
      measured for various operating conditions by varying parameters such as solar
      light intensity and applied electrical voltage. In particular, we observed
      electric-field-driven, carrier transport phenomena (i.e., drift current) in
      modified cells. Fitting with the drift-diffusion model enabled us to extract the
      electric field strengths present in the TiO2 nanoporous layer. 

PMID- 26290999
TI  - Modeling the Ion Selectivity of the Phosphate Specific Channel OprP.
AB  - Ion selectivity of transport systems is an essential property of membranes from
      living organisms. These entities are used to regulate multifarious biological
      processes by virtue of selective participation of specific ions in transport
      processes. To understand this process, we studied the phosphate selectivity of
      the OprP porin from Pseudomonas aeruginosa using all-atom free-energy molecular
      dynamics simulations. These calculations were performed to define the energetics
      of phosphate, sulfate, chloride, and potassium ion transport through OprP. Atomic
      level analysis revealed that the overall electrostatic environment of the channel
      was responsible for the anion selectivity of the channel, whereas the particular
      balance of interactions between the permeating ions and water as well as channel
      residues drove the selectivity between different anions. The selectivity of OprP
      is discussed in light of well-studied ion channels that are highly selective for
      potassium or chloride. 

PMID- 26291000
TI  - Ultrafast Energy Redistribution in Local Hydration Shells of Phospholipids: A Two
      Dimensional Infrared Study.
AB  - Structural and functional properties of phospholipids are strongly influenced by
      dynamics of their hydration shells. Here, we show that local water pools as small
      as three water molecules around the polar headgroups in phospholipid reverse
      micelles (dioleoylphosphatidylcholine, DOPC) serve as efficient sinks of excess
      energy released during vibrational relaxation. Transient two-dimensional (2D)
      infrared spectra of OH stretching excitations of H2O shells demonstrate a
      subpicosecond buildup of a hot water ground state, in which excess energy is
      randomized in low-frequency modes. An analysis of center line slopes of the 2D
      spectra reveals kinetics of energy dissipation that are significantly faster than
      structural fluctuations of the water pool and remain unchanged at intermediate
      hydration levels between three and eight water molecules per polar headgroup. Our
      results suggest that confined small water pools in biomolecular systems are
      sufficient to dissipate excess energy originating from the decay of electronic or
      vibrational excitations. 

PMID- 26291001
TI  - Two-Dimensional Transition Metal Dichalcogenide Alloys: Stability and Electronic
      Properties.
AB  - Using density-functional theory calculations, we study the stability and
      electronic properties of single layers of mixed transition metal dichalcogenides
      (TMDs), such as MoS2xSe2(1-x), which can be referred to as two-dimensional (2D)
      random alloys. We demonstrate that mixed MoS2/MoSe2/MoTe2 compounds are
      thermodynamically stable at room temperature, so that such materials can be
      manufactured using chemical-vapor deposition technique or exfoliated from the
      bulk mixed materials. By applying the effective band structure approach, we
      further study the electronic structure of the mixed 2D compounds and show that
      general features of the band structures are similar to those of their binary
      constituents. The direct gap in these materials can continuously be tuned,
      pointing toward possible applications of 2D TMD alloys in photonics. 

PMID- 26291002
TI  - Atomic-Resolution Structural Dynamics in Crystalline Proteins from NMR and
      Molecular Simulation.
AB  - Solid-state NMR can provide atomic-resolution information about protein motions
      occurring on a vast range of time scales under similar conditions to those of X
      ray diffraction studies and therefore offers a highly complementary approach to
      characterizing the dynamic fluctuations occurring in the crystal. We compare
      experimentally determined dynamic parameters, spin relaxation, chemical shifts,
      and dipolar couplings, to values calculated from a 200 ns MD simulation of
      protein GB1 in its crystalline form, providing insight into the nature of
      structural dynamics occurring within the crystalline lattice. This simulation
      allows us to test the accuracy of commonly applied procedures for the
      interpretation of experimental solid-state relaxation data in terms of dynamic
      modes and time scales. We discover that the potential complexity of relaxation
      active motion can lead to significant under- or overestimation of dynamic
      amplitudes if different components are not taken into consideration. 

PMID- 26291003
TI  - New Directions in Biophysical Modeling.

PMID- 26291004
TI  - Correlated High-Frequency Molecular Motions in Neat Liquid Probed with Ultrafast
      Overtone Two-Dimensional Infrared Spectroscopy.
AB  - In this work, an overtone two-dimensional infrared (2D IR) method is shown to
      allow correlated molecular motions at the frequencies of overtone transitions to
      be studied. Waiting-time-dependent overtone 2D IR results of the C-O stretching
      in neat liquid methanol reveal that the autocorrelation of the v = 0 -> 2
      transition and the cross correlation of the v = 0 -> 2/v = 2 -> 4 transitions
      differ considerably (relaxation time being 700 fs and 2 ps, respectively),
      suggesting different spectral diffusion dynamics. Quantum-chemical computations
      in combination with ab initio molecular dynamics simulations show that the
      overtone transition frequency of the C-O stretching mode in liquid methanol is of
      more structural sensitivity than the fundamental frequency. This work
      demonstrates a new 2D IR approach to examining the structural sensitivities of
      the anharmonic potential parameters of higher vibrational states, which can be
      used to gain new insight into the ultrafast structural dynamics particularly for
      neat liquids. 

PMID- 26291006
TI  - Toward High-Precision Genomic Biomarkers: The Importance of Context.

PMID- 26291007
TI  - Introduction to The 2015 World Health Organization Classification of Tumors of
      the Lung, Pleura, Thymus, and Heart.

PMID- 26291009
TI  - Treatment of Peripheral Non-Small Cell Lung Carcinoma with Stereotactic Body
      Radiation Therapy.
AB  - Stereotactic body radiation therapy (SBRT) is an effective and well-tolerated
      noninvasive treatment for medically inoperable patients with peripheral non-small
      cell lung carcinoma. The term "peripheral" refers to lesions that lie 2 cm or
      more from the mediastinum and proximal bronchial tree and was instituted based on
      results from a specific dose and fractionation schedule. Improvements in
      immobilization, respiratory motion management, and image guidance have allowed
      for SBRT's highly conformal and accurate delivery of large radiation doses per
      fraction. Results from prospective and retrospective studies suggest that lung
      SBRT has superior outcomes when compared with conventionally fractionated
      treatments and is comparable with surgical resection. Investigations into the
      optimal SBRT dosing regimen for peripheral lesions are ongoing, with recent
      trials suggesting comparable efficacy between single and multiple fraction
      schedules. Chest wall toxicity after peripheral treatment is common, but it
      usually resolves with conservative management. Pneumonitis is less often observed
      after treatment of peripheral lesions, and changes in pulmonary function tests
      are minimal. Studies in the frail and elderly suggest that neither baseline
      pulmonary function tests nor age should preclude treatment. Recent technical
      developments have reduced delivery time and resulted in more conformal
      treatments. This review is on behalf of the IASLC Advanced Radiation Technology
      Committee. 

PMID- 26291008
TI  - The 2015 World Health Organization Classification of Lung Tumors: Impact of
      Genetic, Clinical and Radiologic Advances Since the 2004 Classification.
AB  - The 2015 World Health Organization (WHO) Classification of Tumors of the Lung,
      Pleura, Thymus and Heart has just been published with numerous important changes
      from the 2004 WHO classification. The most significant changes in this edition
      involve (1) use of immunohistochemistry throughout the classification, (2) a new
      emphasis on genetic studies, in particular, integration of molecular testing to
      help personalize treatment strategies for advanced lung cancer patients, (3) a
      new classification for small biopsies and cytology similar to that proposed in
      the 2011 Association for the Study of Lung Cancer/American Thoracic
      Society/European Respiratory Society classification, (4) a completely different
      approach to lung adenocarcinoma as proposed by the 2011 Association for the Study
      of Lung Cancer/American Thoracic Society/European Respiratory Society
      classification, (5) restricting the diagnosis of large cell carcinoma only to
      resected tumors that lack any clear morphologic or immunohistochemical
      differentiation with reclassification of the remaining former large cell
      carcinoma subtypes into different categories, (6) reclassifying squamous cell
      carcinomas into keratinizing, nonkeratinizing, and basaloid subtypes with the
      nonkeratinizing tumors requiring immunohistochemistry proof of squamous
      differentiation, (7) grouping of neuroendocrine tumors together in one category,
      (8) adding NUT carcinoma, (9) changing the term sclerosing hemangioma to
      sclerosing pneumocytoma, (10) changing the name hamartoma to "pulmonary
      hamartoma," (11) creating a group of PEComatous tumors that include (a)
      lymphangioleiomyomatosis, (b) PEComa, benign (with clear cell tumor as a variant)
      and 

PMID- 26291011
TI  - Prognostic Factors of Survival after Recurrence in Patients with Resected Lung
      Adenocarcinoma.
AB  - OBJECTIVE: Recurrence after surgical resection is the most common cause of
      treatment failure in patients with non-small-cell lung cancer. The aim of the
      study is to investigate the prognostic factors of postrecurrence survival (PRS)
      in patients of resected lung adenocarcinoma. METHODS: The clinicopathological
      characteristics of 179 patients with recurrence after complete resection of lung
      adenocarcinoma at Taipei Veterans General Hospital between 2004 and 2010 were
      retrospectively reviewed. The prognostic and predictive effects of these
      clinicopathological variables in PRS were analyzed. RESULTS: The pattern of
      recurrence included local only in 25 (15.4%), distant only in 56 (34.6%), and
      both local and distant in 81 (50.0%) of patients. The 2-year and 5-year PRS were
      65.2% and 29.8%, respectively. The most common organ sites of metastasis were the
      contralateral lung (39.1%), followed by the brain (33.5%) and the bone (31.3%).
      Multivariate analysis revealed that micropapillary/solid predominant pattern
      group (versus acinar/papillary; hazard ratio = 2.615; 95% confidence interval:
      1.395-4.901; p = 0.003) and no treatment for recurrence (p < 0.001) were
      significant prognostic factors of worse PRS. For patients receiving treatment for
      recurrence, micropapillary/solid predominant pattern group (versus
      acinar/papillary; hazard ratio = 2.570; 95% confidence interval: 1.357-4.865; p =
      0.004) was a significant predictive factor of worse PRS. Treatment for recurrence
      with surgery (p = 0.067) tended to be a significant predictive factor of better
      PRS. CONCLUSIONS: In lung adenocarcinoma, micropapillary/solid predominant
      pattern group (versus acinar/papillary) was a significant poor prognostic factor
      for PRS.

PMID- 26291010
TI  - Prognostic Impact of Immune Microenvironment in Lung Squamous Cell Carcinoma:
      Tumor-Infiltrating CD10+ Neutrophil/CD20+ Lymphocyte Ratio as an Independent
      Prognostic Factor.
AB  - INTRODUCTION: We previously reported the prognostic significance of the lung
      adenocarcinoma immune microenvironment. In this study, we preformed comprehensive
      analysis of immune markers and their associations with prognosis in patients with
      lung squamous cell carcinoma. METHODS: We reviewed surgically resected, solitary
      lung squamous cell carcinoma patients (n = 485; 1999-2009) who were randomly
      split into a training cohort (n = 331) and validation cohort (n = 154). We
      constructed tissue microarrays and performed immunostaining for CD3, CD45RO, CD8,
      CD4, FoxP3, CD20, CD68, CXCL12, CXCR4, CCR7, interleukin-7 receptor, and
      interleukin-12 receptor beta2. Overall survival (OS) was analyzed using the log
      rank test and the Cox proportional hazards model. RESULTS: Analysis of single
      immune cell infiltration revealed that high tumor-infiltrating CD10(+)
      neutrophils were associated with worse prognoses in the training cohort (p =
      0.021). Analysis of biologically relevant immune cell combinations identified
      that patients with high CD10 neutrophil and low CD20(+) lymphocyte had a
      significantly worse OS (5-year OS, 42%) than those with other combinations of
      CD10 and CD20 (5-year OS, 62%; p < 0.001); this was confirmed in the validation
      cohort (p = 0.032). For the multivariate analysis, high CD10/low CD20 immune cell
      infiltration was an independent predictor of OS in both the training cohort
      (hazard ratio = 1.61, p = 0.006) and the validation cohort (hazard ratio = 1.75;
      p = 0.043). CONCLUSION: High CD10(+)/low CD20(+) immune cell infiltration ratio
      is a significant prognostic factor of lung squamous cell carcinoma.
      Immunomodulatory therapy of tumor-specific neutrophil and B-lymphocyte responses
      may have applicability in the treatment of lung squamous cell carcinoma.

PMID- 26291012
TI  - High-Grade Neuroendocrine Carcinoma with Bronchial Intraepithelial Tumor Spread:
      Possibly a New Histologic Feature of Large-Cell Neuroendocrine Carcinoma.
AB  - INTRODUCTION: During surgical resection of a peripherally located high-grade
      neuroendocrine carcinoma (HGNEC), we unexpectedly discovered prominent bronchial
      intraepithelial tumor spread up to the surgical end of the bronchus. Because
      bronchial intraepithelial tumor spread of peripherally located HGNEC has been
      rarely reported, we conducted a retrospective analysis at our hospital. METHODS:
      We histologically reviewed surgically resected HGNEC cases to assess bronchial
      intraepithelial spread of tumor cells. HGNECs with bronchial intraepithelial
      tumor spread were further studied by immunohistochemistry for neuroendocrine
      markers, and their clinicopathological characteristics were evaluated. RESULTS:
      Of 1778 cases of surgically resected lung cancer in our hospital, 47 cases of
      HGNEC were evaluated. Bronchial intraepithelial tumor spread was observed in nine
      cases (19.1%); eight of these cases were large-cell neuroendocrine carcinoma
      (LCNEC) or small-cell lung carcinoma with an LCNEC component. Moreover, bronchial
      intraepithelial tumor spread was continuous from the primary tumor to the
      resected end of the bronchus in four cases, and all these cases had an LCNEC
      component. Furthermore, HGNEC with bronchial intraepithelial tumor spread was
      associated with a higher recurrence rate than no bronchial intraepithelial tumor
      spread. CONCLUSION: The results of this study suggest that bronchial
      intraepithelial tumor spread is commonly observed in cases of peripherally
      located HGNEC and may be a unique form of tumor invasion, especially tumors with
      LCNEC morphology. Therefore, surgeons and pathologists should be cognizant of
      bronchial intraepithelial tumor spread in peripherally located HGNEC, as well as
      its potential role as an indicator of HGNEC aggressiveness.

PMID- 26291013
TI  - PTPRF Expression as a Potential Prognostic/Predictive Marker for Treatment with
      Erlotinib in Non-Small-Cell Lung Cancer.
AB  - INTRODUCTION: EGFR mutations and anaplastic lymphoma kinase rearrangements are,
      to date, the only approved biomarkers to select treatment for non-small-cell lung
      cancer (NSCLC). However, there is considerable interest in identifying other
      predictive markers. The PTPRF gene has been suggested as a marker of interest in
      NSCLC and other tumor types. METHODS: This hypothesis-generating retrospective
      analysis examined data from two studies of erlotinib in NSCLC, Marker
      Identification Trial (MERIT; n = 102) and Sequential Tarceva in Unresectable
      NSCLC (SATURN; n = 262), to determine whether PTPRF expression was prognostic
      and/or predictive of patient outcomes. Exploratory analyses were conducted using
      quantitative reverse transcription polymerase chain reaction on existing formalin
      fixed paraffin-embedded samples, to assess gene expression levels, including
      PTPRF. High versus low levels of expression were dichotomized using the median
      with B2M as a control comparator. Progression-free survival and overall survival
      were then compared for patients with high versus low levels of PTPRF in the two
      studies. RESULTS: PTPRF expression was found to be prognostic for shorter overall
      survival but was also significantly predictive of improved survival with
      erlotinib versus placebo in SATURN (hazard ratio, 0.45 [95% confidence interval,
      CI, 0.30-0.69] in PTPRF high versus 0.96 [95% CI, 0.62-1.48] in PTPRF low;
      interaction p = 0.02), even in the EGFR wild-type subpopulation (adjusted hazard
      ratio, 0.44 [95% CI, 0.29-0.68] versus 0.96 [95% CI, 0.62-1.48]; interaction p =
      0.01). CONCLUSIONS: PTPRF may have value as a predictive marker to identify which
      patients can obtain the greatest benefit from erlotinib in the post-first-line
      setting. Further research is warranted to determine the potential value of this
      marker in clinical decision-making.

PMID- 26291014
TI  - Epidermal Growth Factor Receptor Mutation-Positive Non-Small-Cell Lung Cancer in
      the Real-World Setting in Central Europe: The INSIGHT Study.
AB  - The ImplementatioN of perSonalized medicine In NSCLC in Central Europe: EGFR
      testing, Histopathology, and clinical feaTures (INSIGHT) observational study
      assessed both implementation of epidermal growth factor receptor (EGFR) mutation
      testing and treatment of patients with advanced EGFR mutation-positive non-small
      cell lung cancer (NSCLC) in a real-world setting in Central Europe. A total of
      1785 patients from 14 cancer centers of six Central European countries were
      enrolled. EGFR mutations were detected in tumors of 13.8% of the patients. More
      than 70% of patients with advanced EGFR mutation-positive NSCLC received EGFR
      tyrosine kinase inhibitors as first-line therapy. The INSIGHT study demonstrated
      the establishment of EGFR mutation testing, a mutation rate consistent with other
      Caucasian patients populations, and adherence to current guidelines regarding
      treatment of patients with EGFR mutation-positive tumors in Central Europe. 

PMID- 26291015
TI  - The Moth-Eaten Lung: Lung Adenocarcinoma with Cavitating Miliary Intrapulmonary
      Carcinomatosis.

PMID- 26291016
TI  - Lungs on Fire.

PMID- 26291017
TI  - Histologic Transformation from Adenocarcinoma to Squamous Cell Carcinoma as a
      Mechanism of Resistance to EGFR Inhibition.

PMID- 26291018
TI  - Pneumonectomy-Sparing NSAID Therapy for Pulmonary Inflammatory Myofibroblastic
      Tumor.

PMID- 26291019
TI  - Are We at the Dusk of Mediastinoscopy in Modern Clinical Practice?

PMID- 26291020
TI  - Reply to "Are We at the Dusk of Mediastinoscopy in Modern Clinical Practice?": An
      Irresistible Trend.

PMID- 26291021
TI  - Surgery and Survival of Patients with Diagnosis of Malignant Pleural
      Mesothelioma.

PMID- 26291022
TI  - In Response.

PMID- 26291023
TI  - Rapid Response to Sunitinib in a Patient with Lung Adenocarcinoma Harboring KIF5B
      RET Fusion Gene.

PMID- 26291025
TI  - Coffee prevents proximal colorectal adenomas in Japanese men: a prospective
      cohort study.
AB  - This prospective cohort study aimed to show that coffee prevents the recurrence
      of colorectal tumors (adenomas, precursors of colorectal cancer, and early-stage
      colorectal cancers) as well as colorectal cancer. The present study included 307
      patients who participated in a clinical study that required endoscopy to remove a
      colorectal tumor. The amount of coffee consumed by the patients at study
      inclusion and the frequency of colorectal tumors, as detected by colonoscopy over
      the subsequent 4 years, were assessed. Coffee consumption was determined using a
      diet survey that included 3-consecutive-day food records. The risk of colorectal
      tumor recurrence was significantly lower (odds ratio=0.21; 95% confidence
      interval, 0.06-0.74) in patients who consumed more than three cups of coffee per
      day compared with those who consumed no coffee. No correlation was observed
      between the examined factors, including green tea and black tea intake and the
      amount of caffeine consumed. In subanalysis divided by the tumor location within
      the colorectum, the odds ratio of colorectal tumor recurrence in the proximal
      colon showed a tendency toward reduction as coffee consumption increased;
      however, increased coffee consumption significantly increased colorectal tumor
      recurrence in the distal colon. We showed that high coffee consumption reduced
      the overall occurrence of colorectal tumors, affected by the reduction in the
      proximal colon.

PMID- 26291024
TI  - Toward the complete characterization of host cell proteins in biotherapeutics via
      affinity depletions, LC-MS/MS, and multivariate analysis.
AB  - Host cell protein (HCP) impurities are generated by the host organism during the
      production of therapeutic recombinant proteins, and are difficult to remove
      completely. Though commonly present in small quantities, if levels are not
      controlled, HCPs can potentially reduce drug efficacy and cause adverse patient
      reactions. A high resolution approach for thorough HCP characterization of
      therapeutic monoclonal antibodies is presented herein. In this method, antibody
      samples are first depleted via affinity enrichment (e.g., Protein A, Protein L)
      using milligram quantities of material. The HCP-containing flow-through is then
      enzymatically digested, analyzed using nano-UPLC-MS/MS, and proteins are
      identified through database searching. Nearly 700 HCPs were identified from
      samples with very low total HCP levels (< 1 ppm to ~ 10 ppm) using this method.
      Quantitation of individual HCPs was performed using normalized spectral counting
      as the number of peptide spectrum matches (PSMs) per protein is proportional to
      protein abundance. Multivariate analysis tools were utilized to assess
      similarities between HCP profiles by: 1) quantifying overlaps between HCP
      identities; and 2) comparing correlations between individual protein abundances
      as calculated by spectral counts. Clustering analysis using these measures of
      dissimilarity between HCP profiles enabled high resolution differentiation of
      commercial grade monoclonal antibody samples generated from different cell lines,
      cell culture, and purification processes.

PMID- 26291026
TI  - Establishing the human naive pluripotent state.
AB  - Pluripotency is first assembled within the inner-cell-mass of developing pre
      implantation blastocysts, and is gradually reconfigured and dismantled during
      early post-implantation development, before overt differentiation into somatic
      lineages ensues. This transition from pre-implantation to post-implantation
      pluripotent states, respectively referred to as naive and primed, is accompanied
      by dramatic changes in molecular and functional characteristics. Remarkably,
      pluripotent states can be artificially preserved in a self-renewing state in
      vitro by continuous supplementation of a variety of exogenous cytokines and small
      molecule inhibitors. Different exogenous factors endow the cells with distinct
      configurations of pluripotency that have direct influence on stem cell
      characteristics both in mice and humans. Here we overview pluripotent states
      captured from rodents and humans under different growth conditions, and provide a
      conceptual framework for classifying pluripotent cell states on the basis of a
      combination of multiple characteristics that a pluripotent cell can
      simultaneously retain. We further highlight the complexity and dynamic nature of
      these artificially isolated in vitro pluripotent states in humans. 

PMID- 26291027
TI  - Development of Thermally Activated Delayed Fluorescence Materials with Shortened
      Emissive Lifetimes.
AB  - We have prepared a thermally activated delayed fluorescence (TADF) capable
      molecular system carrying halogen substituents at the carbazole units. The
      attachment of the halogen atoms considerably decreases the half-life of the
      delayed fluorescence. The effect is significant. The heavier the halogen, the
      greater the effect. Our materials have the shortest reported emissive lifetimes
      for TADF achieved to date. Intersystem crossing (ISC) is improved through the
      heavy atom effect, yet high quantum yields are achieved both in solution as well
      as in thin doped films. The simple and efficient synthesis of our targets uses
      inexpensive and easily obtained starting materials. 

PMID- 26291028
TI  - Effect of shock waves on macrophages: A possible role in tissue regeneration and
      remodeling.
AB  - INTRODUCTION: Extracorporeal Shock Wave Therapy (ESWT) is broadly used as a non
      surgical therapy in various diseases for its pro-angiogenic and anti-inflammatory
      effects. However, the molecular mechanisms translating tissue exposure to shock
      waves (SW) in a biological response with potential therapeutic activity are
      largely unknown. As macrophages take part in both the onset and amplification of
      the inflammatory response, and well in its resolution, we investigated the effect
      of SW on their biology. METHODS: Human monocyte-derived macrophages were
      polarized to classic (M1) pro-inflammatory macrophages or alternative (M2) anti
      inflammatory macrophages and exposed to SW ad different intensities. Expression
      levels of marker genes of macrophage activation were measured by qPCR at
      different time points. RESULTS: SW did not induce activation of resting
      macrophages at any energy level used. Conversely, when used at low energy SW
      caused a significant inhibition of some M1 marker genes (CD80, COX2, CCL5) in M1
      macrophages and a significant synergistic effect for some M2 marker genes
      (ALOX15, MRC1, CCL18) in M2 macrophages. SW also affected cytokine and chemokine
      production, inducing in particular a significant increase in IL-10 and reduction
      in IL-1beta production. CONCLUSIONS: Macrophage exposure to low energy SW dampens
      the induction of the pro-inflammatory profile characterizing M1 macrophages and
      promotes the acquisition of an anti-inflammatory profile synergizing with
      macrophage alternative activation.

PMID- 26291029
TI  - Performing the Bakla in The Care Divas: Crossdressing, Affective Labor, and the
      Glimpse of the Cosmopolitan.
AB  - This essay is a close reading of The Care Divas, a Filipino musical revolving
      around the struggle of five Filipino caregivers in Israel who also struggle with
      their sexual identities as bakla (Filipino homosexual). The analysis is both an
      affirmation and a critique of the performance. In the affirmation, the musical is
      argued to present a social reality that is intended for and in need of
      interrogation: the Filipino bakla. The musical implicitly features the bakla as a
      cosmopolitan. At the outset, this cosmopolitan disposition comes from the fact
      that the characters are migrant workers (caregivers). But more importantly, the
      cosmopolitan character is from a responsibility toward the other anchored within
      a genuine caring as implicated in the affective labor of these caregiver
      characters. In the critique, the essay marks some problematic limitations in the
      treatment of the bakla. In doing so, the musical, despite its attempt to present
      a social reality, is a problem play, a social drama touching social issues-
      realistic in approach, but the representation seems like an editorial. In the
      final analysis, The Care Divas is argued to seemingly fail because artists are
      not able to see the complexity of their chosen subject in a bigger picture.

PMID- 26291030
TI  - Topology Optimized Architectures with Programmable Poisson's Ratio over Large
      Deformations.
AB  - Topology optimized architectures are designed and printed with programmable
      Poisson's ratios ranging from -0.8 to 0.8 over large deformations of 20% or more.

PMID- 26291033
TI  - A generalized method for the inversion of cohesive energy curves from isotropic
      and anisotropic lattice expansions.
AB  - Cohesive energy curves contain important information about energetics of atomic
      interactions in crystalline materials, and these are more often obtained using ab
      initio methods such as density functional theory. Decomposing these curves into
      the different interatomic contributions is of great value to evaluate and
      characterize the energetics of specific types of atom-atom interactions. In this
      work, we present and discuss a generalized method for the inversion of cohesive
      energy curves of crystalline materials for pairwise interatomic potentials
      extraction using detailed geometrical descriptions of the atomic interactions to
      construct a list of atomic displacements and degeneracies, which is modified
      using a Gaussian elimination process to isolate the pairwise interactions. The
      proposed method provides a more general framework for cohesive energy inversions
      that is robust and accurate for systems well-described by pairwise potential
      interactions. Results show very good reproduction of cohesive energies with the
      same or better accuracy than current approaches with the advantage that the
      method has broader applications. 

PMID- 26291031
TI  - Long-term Functional Outcomes of Total Glossectomy With or Without Total
      Laryngectomy.
AB  - IMPORTANCE: The optimal reconstruction of total glossectomy defects with or
      without total laryngectomy is controversial. Various pedicled and free tissue
      flaps have been advocated, but long-term data on functional outcomes are not
      available to date. OBJECTIVES: To compare various total glossectomy defect
      reconstructive techniques used by multiple institutions and to identify factors
      that may lead to improved long-term speech and swallowing function. DESIGN,
      SETTING, AND PARTICIPANTS: A multi-institutional, retrospective review of
      electronic medical records of patients undergoing total glossectomy at 8
      participating institutions between June 1, 2001, and June 30, 2011, who had a
      minimal survival of 2 years. INTERVENTION: Total glossectomy with or without
      total laryngectomy. MAIN OUTCOMES AND MEASURES: Demographic and surgical factors
      were compiled and correlated with speech and swallowing outcomes. RESULTS: At the
      time of the last follow-up, 45% (25 of 55) of patients did not have a gastrostomy
      tube, and 76% (42 of 55) retained the ability to verbally communicate. Overall,
      75% (41 of 55) of patients were tolerating at least minimal nutritional oral
      intake. Feeding tube dependence was not associated with laryngeal preservation or
      the reconstructive techniques used, including flap suspension, flap innervation,
      or type of flap used. Laryngeal preservation was associated with favorable speech
      outcomes, such as the retained ability to verbally communicate in 97% of those
      not undergoing total laryngectomy (35 of 36 patients) vs 44% (7 of 16) in those
      undergoing total laryngectomy (P < .001), as well as those not undergoing total
      laryngectomy achieving some or all intelligible speech in 85% (29 of 34 patients)
      compared with 31% (4 of 13) undergoing total laryngectomy achieving the same
      intelligibility (P < .001). CONCLUSIONS AND RELEVANCE: In patients with total
      glossectomy, feeding tube dependence was not associated with laryngeal
      preservation or the reconstructive technique, including flap innervation and type
      of flap used. Laryngeal preservation was associated with favorable speech
      outcomes such as the retained ability to verbally communicate and higher levels
      of speech intelligibility.

PMID- 26291032
TI  - Alterations of plasma glycerophospholipid and sphingolipid species in male
      alcohol-dependent patients.
AB  - BACKGROUND: Alcohol abuse is a major risk factor for somatic and neuropsychiatric
      diseases. Despite their potential clinical importance, little is known about the
      alterations of plasma glycerophospholipid (GPL) and sphingolipid (SPL) species
      associated with alcohol abuse. METHODS: Plasma GPL and SPL species were
      quantified using electrospray ionization tandem mass spectrometry in samples from
      23 male alcohol-dependent patients before and after detoxification, as well as
      from 20 healthy male controls. RESULTS: A comparison of alcohol-dependent
      patients with controls revealed higher phosphatidylcholine (PC; P-value=0.008)
      and phosphatidylinositol (PI; P-value=0.001) concentrations in patients before
      detoxification, and higher PI (P-value=0.001) and phosphatidylethanolamine (PE)
      based plasmalogen (PE P; P-value=0.003) concentrations after detoxification.
      Lysophosphatidylcholines (LPC) were increased by acute intoxication (P
      value=0.002). Sphingomyelin (SM) concentration increased during detoxification (P
      value=0.011). The concentration of SM 23:0 was lower in patients (P
      value=2.79*10(-5)), and the concentrations of ceramide Cer d18:1/16:0 and Cer
      d18:1/18:0 were higher in patients (P-value=2.45*10(-5) and 3.73*10(-5)).
      Activity of lysosomal acid sphingomyelinase (ASM) in patients correlated
      positively with the concentrations of eight LPC species, while activity of
      secreted ASM was inversely correlated with several PE, PI and PC species, and
      positively correlated with the molar ratio of PC to SM (Pearson's r=-0.432; P
      value=0.039). CONCLUSION: Plasma concentrations of numerous GPL and SPL species
      were altered in alcohol-dependent patients. These molecules might serve as
      potential biomarkers to improve the diagnosis of patients and to indicate health
      risks associated with alcohol abuse. Our study further indicates that there are
      strong interactions between plasma GPL concentrations and SPL metabolism.

PMID- 26291034
TI  - Phosphorylation of Elg1 regulates its activity.

PMID- 26291035
TI  - Evaluating Epidemiology and Improving Surveillance of Infections Associated with
      Health Care, United States.
AB  - The Healthcare-Associated Infections Community Interface (HAIC), launched in
      2009, is the newest major activity of the Emerging Infections Program. The HAIC
      activity addresses population- and laboratory-based surveillance for Clostridium
      difficile infections, candidemia, and multidrug-resistant gram-negative bacilli.
      Other activities include special projects: the multistate Healthcare-Associated
      Infections and Antimicrobial Use Prevalence Survey and projects that evaluate new
      approaches for improving surveillance. The HAIC activity has provided information
      about the epidemiology and adverse health outcomes of health care-associated
      infections and antimicrobial drug use in the United States and informs efforts to
      improve patient safety through prevention of these infections. 

PMID- 26291036
TI  - Synthesis and antiviral activity of some new bis-1,3-thiazole derivatives.
AB  - Treatment of 3-phenyl-1,3-thiazolidin-4-one derivative 1 with
      phenylisothiocyanate in DMF, in the presence of potassium hydroxide, at room
      temperature gave the non-isolable potassium salt 2. The in-situ reaction of 2
      with differently substituted N-aryl hydrazonoyl chlorides 3, 7a-d and 14a-d
      afforded the corresponding 2-(pyrazolyl)thiazolylimino-5
      (thiadiazolylidene)thiazolidin-4-one derivatives 6, 10a-d and 17a-d,
      respectively. Reaction of 2 with further alpha-haloketones yielded the 4
      (pyrazolyl)thiazolylimino-bis-thiazolidine derivatives 22, 25 and 26. Single
      crystal X-ray analysis was used in structure elucidation of the products. The in
      vitro antiviral screening against four viruses (Poliovirus, Influenza A (H1N1)
      virus, Hepatitis B virus and Hepatitis C virus) for the obtained compounds was
      examined. Structure activity relationship (SAR) was also studied. The goal of the
      work was achieved in discovering a very active compound 10a as anti HCV agent
      (EC50 0.56 MUM).

PMID- 26291037
TI  - Design and synthesis of 2-phenylnaphthalenoids and 2-phenylbenzofuranoids as DNA
      topoisomerase inhibitors and antitumor agents.
AB  - Eight 2-phenylnaphthalenoids (2PNs) (3a-h) and twenty four 2-phenylbenzofuranoids
      (2PBFs) (4a--4j, 5a-5j, 6a, 6f-6h) were successfully designed, synthesized and
      their antiproliferative and in vitro DNA topoisomerase inhibitory activities were
      evaluated. Nine compounds (four 2PNs and five 2PBFs) showed either TopoI or
      TopoIIalpha inhibitory activities. Six compounds (four 2PNs and two 2PBFs)
      exhibited potent cytotoxicity with IC50 values for 72 h exposure ranging from 0.3
      to above 20 MUM against MDA-MB-231, MDA-MB-435, HepG2 and PC3 cell lines. The two
      2PBFs displayed comparable and even better antiproliferative as well as
      TopoIIalpha inhibitory activities than 2PNs. Interestingly, the active 2PBFs
      displayed different mechanisms of TopoIIalpha inhibition from that of 2PNs,
      suggesting that the chromophore scaffold replacement may result in a change of
      the binding site of inhibitors to TopoIIalpha. Furthermore, the mechanisms of
      antiproliferation on MDA-MB-231 cells indicate that compounds 5a and 5f are
      promising for further development of anticancer agents. The results of this study
      reveal that the evolutionary strategy of medicinal chemistry through scaffold
      hopping is a promising strategy for structure optimization of TopoIIalpha
      inhibitors.

PMID- 26291038
TI  - Novel halogenated 3-deazapurine, 7-deazapurine and alkylated 9-deazapurine
      derivatives of L-ascorbic or imino-L-ascorbic acid: Synthesis, antitumour and
      antiviral activity evaluations.
AB  - Keeping the potential synergy of biological activity of synthetic anomalous
      derivatives of deazapurines and l-ascorbic acid (l-AA) in mind, we have
      synthesized new 3-, 7- and 9-deazapurine derivatives of l-ascorbic (1-4, 8-10, 13
      15) and imino-l-ascorbic acid (5-7, 11, 12, 16-19). These novel compounds were
      evaluated for their cytostatic and antiviral activity in vitro against a panel of
      human malignant tumour cell lines and normal murine fibroblasts (3T3). Among all
      evaluated compounds, the 9-deazapurine derivative of l-AA (13) exerted the most
      potent inhibitory activity on the growth of CEM/0 cells (IC50 = 4.1 +/- 1.8 MUM)
      and strong antiproliferative effect against L1210/0 (IC50 = 4.7 +/- 0.1 MUM)
      while the 9-deazahypoxanthine derivative of l-AA (15) showed the best effect
      against HeLa cells (IC50 = 5.6 +/- 1.3 MUM) and prominent effect on L1210/0 (IC50
      = 4.5 +/- 0.5 MUM). Furthermore, the 9-deazapurine derivative disubstituted with
      two imino-l-AA moieties (18) showed the best activity against L1210/0 tumour
      cells (IC50 = 4.4 +/- 0.3 MUM) and the most pronounced antiproliferative effects
      against MiaPaCa-2 cells (IC50 = 5.7 +/- 0.2 MUM). All these compounds showed
      selective cytostatic effect on tumour cell lines in comparison with embryonal
      murine fibroblasts (3T3). When evaluating their antiviral activity, the 3
      deazapurine derivative of l-AA (3) exhibited the highest activity against both
      laboratory-adapted strains of human cytomegalovirus (HCMV) (AD-169 and Davis)
      with EC50 values comparable to those of the well-known anti-HCMV drug ganciclovir
      and without cytotoxic effects on normal human embryonal lung (HEL) cells.

PMID- 26291040
TI  - Observation versus inpatient hospitalization: What do Medicare beneficiaries pay?

PMID- 26291039
TI  - Design and synthesis of novel hydroxyanthraquinone nitrogen mustard derivatives
      as potential anticancer agents via a bioisostere approach.
AB  - A series of hydroxyanthraquinones having an alkylating N-mustard pharmacophore at
      1'-position were synthesized via a bioisostere approach to evaluate their
      cytotoxicity against four tumor cell lines (MDA-MB-231, HeLa, MCF-7 and A549).
      These compounds displayed significant in vitro cytotoxicity against MDA-MB-231
      and MCF-7 cells, reflecting the excellent selectivity for the human breast
      cancer. Among them, compound 5k was the most cytotoxic with IC50 value of 0.263
      nM and is more potent than DXR (IC50 = 0.294 nM) in inhibiting the growth of MCF
      7 cells. The excellent cytotoxicity and good selectivity of compound 5k suggest
      that it could be a promising lead for further design and development of
      anticancer agents, especially for breast cancer.

PMID- 26291041
TI  - High-Resolution Measurements of Velocity and Shear Stress in Leakage Jets From
      Bileaflet Mechanical Heart Valve Hinge Models.
AB  - In flow through cardiovascular implants, hemolysis, and thrombosis may be
      initiated by nonphysiological shear stress on blood elements. To enhance
      understanding of the small-scale flow structures that stimulate cellular
      responses, and ultimately to design devices for reduced blood damage, it is
      necessary to study the flow-field at high spatial and temporal resolution. In
      this work, we investigate flow in the reverse leakage jet from the hinge of a
      bileaflet mechanical heart valve (BMHV). Scaled-up model hinges are employed,
      enabling measurement of the flow-field at effective spatial resolution of 167 MUm
      and temporal resolution of 594 MUs using two-component particle image velocimetry
      (PIV). High-velocity jets were observed at the hinge outflow, with time-average
      velocity up to 5.7 m/s, higher than reported in previous literature. Mean viscous
      shear stress is up to 60 Pa. For the first time, strongly unsteady flow has been
      observed in the leakage jet. Peak instantaneous shear stress is up to 120 Pa,
      twice as high as the average value. These high-resolution measurements identify
      the hinge leakage jet as a region of very high fluctuating shear stress which is
      likely to be thrombogenic and should be an important target for future design
      improvement. 

PMID- 26291042
TI  - Splenic melanosis in agouti and black mice.
AB  - An interesting example of extradermal deposition of melanin in vertebrates,
      notably in mammals, is splenic melanosis. In particular, if the phenomenon of
      splenic melanosis is correlated with hair or skin pigmentation, it must reflect
      the amount and perhaps the quality of pigment produced in hair follicle
      melanocytes. The present paper is our first study on splenic pigmentation in mice
      of phenotype agouti. We used untreated mixed background mice C57BL/6;129/SvJ
      (black - a/a, agouti - A/a, A/A), and as a control - black C57BL/6 and agouti fur
      from 129/SvJ mice, Mongolian gerbils (Meriones unguiculatus) and golden hamsters
      (Mesocricetus auratus). After euthanasia skin and spleen was evaluated
      macroscopically, photographed and collected for further analysis using Fontana
      Masson and hematoxylin-eosin staining and electron paramagnetic resonance (EPR)
      at X-band. Spleens of the agouti mice revealed splenic melanosis but were
      slightly weaker pigmented than their black counterparts, while the presence of
      pheomelanin was difficult to determine. The fur of both phenotypes was of similar
      melanin content, with the same tendency as in the spleens. The contribution of
      pheomelanin in the agouti fur was on the border of detectability by EPR.
      Histological and EPR analysis confirmed the presence of melanin in the melanotic
      spleens. The shape of the EPR signal showed a dominance of eumelanin in fur and
      in melanized spleens in both phenotypes of mice. Therefore, splenic melanosis
      does reflect the hair follicle pigmentation not only in black, but also in agouti
      mice. 

PMID- 26291043
TI  - Selected mucolytic, anti-inflammatory and cardiovascular drugs change the ability
      of neutrophils to form extracellular traps (NETs).
AB  - Neutrophils form the first line of host defense against infections that combat
      pathogens using two major mechanisms, the phagocytosis or the release of
      neutrophil extracellular traps (NETs). The netosis (NET formation) exerts
      additional, unfavorable effects on the fitness of host cells and is also involved
      at the sites of lung infection, increasing the mucus viscosity and in the
      circulatory system where it can influence the intravascular clot formation.
      Although molecular mechanisms underlying the netosis are still incompletely
      understood, a role of NADPH oxidase that activates the production of reactive
      oxygen species (ROS) during the initiation of NETs has been well documented.
      Since several commonly used drugs can affects the netosis, our current study was
      aimed to determine the effects of selected mucolytic, anti-inflammatory and
      cardiovascular drugs on NET formation, with a special emphasis on ROS production
      and NADPH oxidase activity. The treatment of neutrophils with N-acetylcysteine,
      ketoprofen and ethamsylate reduced the production of ROS by these cells in a dose
      dependent manner. NET formation was also modulated by selected drugs. N
      acetylcysteine inhibited the netosis but in the presence of H2O2 this neutrophil
      ability was restored, indicating that N-acetylcysteine may influence the NET
      formation by modulating ROS productivity. The administration of ethamsylate led
      to a significant reduction in NET formation and this effect was not restored by
      H2O2 or S. aureus, suggesting the unexpected additional side effects of this
      drug. Ketoprofen seemed to promote ROS-independent NET release, simultaneously
      inhibiting ROS production. The results, obtained in this study strongly suggest
      that the therapeutic strategies applied in many neutrophil-mediated diseases
      should take into account the NET-associated effects. 

PMID- 26291044
TI  - Properties of water hydrating the galactolipid and phospholipid bilayers: a
      molecular dynamics simulation study.
AB  - Molecular dynamics simulations of 1,2-di-O-acyl-3-O-beta-D-galactopyranosyl-sn
      glycerol (MGDG) and 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) bilayers
      were carried out to compare the effect of the lipid head group's chemical
      structure on the dynamics and orientational order of the water molecules
      hydrating the bilayer. The effect of the bilayers on the diffusion of water is
      strong for the neighbouring water molecules i.e., those located not further than
      4 A from any bilayer atom. This is because the neighbouring water molecules are
      predominantly hydrogen bonded to the lipid oxygen atoms and their mobility is
      limited to a confined spatial volume. The choline group of DOPC and the galactose
      group of MGDG affect water diffusion less than the polar groups located deeper in
      the bilayer interface, and similarly. The latter is an unexpected result since
      interactions of water with these groups have a vastly different origin. The least
      affected by the bilayer lipids is the lateral diffusion of unbound water in the
      bilayer plane (x,y-plane) - it is because the diffusion is not confined by the
      periodic boundary conditions, whereas that perpendicular to the plane is.
      Interactions of water molecules with lipid groups also enforce certain
      orientations of water dipole moments. The profile of an average water orientation
      along the bilayer normal for the MGDG bilayer differs from that for the DOPC
      bilayer. In the DOPC bilayer, the ordering effect of the lipid head groups
      extends further into the water phase than in the MGDG bilayer, whereas inside the
      bilayer/water interface, ordering of the water dipoles in the MGDG bilayer is
      higher. It is possible that differences in the profiles of an average water
      orientation across the bilayer in the DOPC and MGDG bilayers are responsible for
      differences in the lateral pressure profiles of these bilayers. 

PMID- 26291045
TI  - A novel multivariate performance optimization method based on sparse coding and
      hyper-predictor learning.
AB  - In this paper, we investigate the problem of optimization of multivariate
      performance measures, and propose a novel algorithm for it. Different from
      traditional machine learning methods which optimize simple loss functions to
      learn prediction function, the problem studied in this paper is how to learn
      effective hyper-predictor for a tuple of data points, so that a complex loss
      function corresponding to a multivariate performance measure can be minimized. We
      propose to present the tuple of data points to a tuple of sparse codes via a
      dictionary, and then apply a linear function to compare a sparse code against a
      given candidate class label. To learn the dictionary, sparse codes, and parameter
      of the linear function, we propose a joint optimization problem. In this problem,
      the both the reconstruction error and sparsity of sparse code, and the upper
      bound of the complex loss function are minimized. Moreover, the upper bound of
      the loss function is approximated by the sparse codes and the linear function
      parameter. To optimize this problem, we develop an iterative algorithm based on
      descent gradient methods to learn the sparse codes and hyper-predictor parameter
      alternately. Experiment results on some benchmark data sets show the advantage of
      the proposed methods over other state-of-the-art algorithms. 

PMID- 26291046
TI  - Symmetry symptoms in obsessive-compulsive disorder: clinical and genetic
      correlates.
AB  - OBJECTIVE: In obsessive-compulsive disorder (OCD), symmetry-related symptoms may
      be important. Although clinical correlates of symmetry-related symptoms have been
      identified in OCD, few data exist on genetic associations. Animal studies
      indicate involvement of dopamine in symmetry-related behavior, suggesting this
      may be relevant to analogous symptoms in OCD. Alterations in dopamine may also
      reflect environmental influences. However, the association of symmetry-related
      symptomatology, early adversity, and polymorphisms in dopaminergic genes has not
      been investigated in OCD. METHODS: Clinical information and polymorphisms in key
      dopaminergic genes were compared between OCD patients with primary symmetry
      symptoms and those without. RESULTS: OCD patients with primary symmetry symptoms
      comprised 46.6% (n=210) of the sample (n=451), and were older (p < 0.01), had
      longer illness duration (p < 0.01), higher OCD severity scores (p = 0.01), and
      greater comorbidity (p < 0.01) than those without. In Caucasians (n=343),
      genotype frequency differed significantly between groups for ANKK1 rs1800497,
      with more OCD patients with symmetry symptoms being homozygous for the A2 (CC)
      genotype (chi2 = 7.296; p = 0.026). CONCLUSION: Symmetry symptoms have some
      distinct clinical features and may represent a marker of severity in OCD.
      However, clinical associations, in combination with the association found with
      the ANKK1 rs1800497 A2 variant, suggest that primary symmetry symptoms may
      represent a distinctive clinical and psychobiological profile.

PMID- 26291047
TI  - Laparoscopic management of a cystic artery pseudoaneurysm in a patient with
      calculus cholecystitis.
AB  - INTRODUCTION: Pseudoaneurysm of the cystic artery is very rare. In the majority
      of cases it has been reported as a post-operative complication of laparoscopic
      cholecystectomy, however it has also been associated with the presence of acute
      cholecystitis or pancreatitis. When these pseudoaneurysms rupture they can lead
      to intraperitoneal bleeding, haemobilia and upper gastrointestinal haemorrhage.
      Radiological as well as open surgical approaches have been described for control
      of this rare pathology. PRESENTATION OF CASE: We report the laparoscopic surgical
      management of an incidental, unruptured cystic artery pseudoaneurysm in a patient
      presenting with acute cholecystitis. DISCUSSION: Cystic artery pseudoaneurysm is
      a rare entity and as such there is no consensus on the clinical management of
      this condition. A variety of treatment strategies have been reported in the
      literature including radiological selective embolisation and coiling, open
      cholecystectomy with ligation of the aneurysm, or a two-step approach involving
      radiological management of the pseudoaneurysm followed by an elective
      cholecystectomy. CONCLUSION: In this report we have demonstrated that
      laparoscopic management of a cystic artery pseudoaneurysm with simultaneous
      laparoscopic cholecystectomy is feasible and safe. This avoids multiple invasive
      procedures and decreases morbidity associated with open surgery.

PMID- 26291048
TI  - Emergency Department Evaluation And Management Of Patients With Upper
      Gastrointestinal Bleeding.
AB  - Upper gastrointestinal bleeding results from a variety of conditions that may
      vary in severity from merely bothersome to imminently life-threatening. While
      stabilization is standard for nearly all causes of bleeding, identifying whether
      the bleed is from variceal or nonvariceal sources is critical. Testing and
      treatments such as nasogastric lavage, antibiotics, somatostatin analogues,
      proton pump inhibitors, and emergent endoscopy may benefit some patients,
      depending upon the bleeding source and other clinical factors; however, some
      therapies that are routinely used have very little evidence demonstrating
      effectiveness. This issue reviews the most recent evidence regarding appropriate
      testing, risk stratification, and indications for gastroenterology consult in the
      emergency department in order to treat these patients appropriately.

PMID- 26291049
TI  - Critical evaluation of national vital statistics: the case of preterm birth
      trends in Portugal.
AB  - INTRODUCTION: Using vital statistics, the Portuguese National Health Plan
      predicts that 14% of live births will be preterm in 2016. The prediction was
      based on a preterm birth rise from 5.9% in 2000 to 8.8% in 2009. However, the
      same source showed an actual decline from 2010 onwards. To assess the
      plausibility of national preterm birth trends, we aimed to compare the evolution
      of preterm birth and low birthweight rates between vital statistics and a
      hospital database. MATERIAL AND METHODS: A time-trend analysis (2004-2011) of
      preterm birth (<37 gestational weeks) and low birthweight (<2500 g) rates was
      conducted using data on singleton births from the national birth certificates (n
      = 801,783) and an electronic maternity unit database (n = 21,392). Annual
      prevalence estimates, ratios of preterm birth:low birthweight and adjusted
      prevalence ratios were estimated to compare data sources. RESULTS: Although the
      national prevalence of preterm birth increased from 2004 (5.4%), particularly
      between 2006 and 2009 (highest rate was 7.5% in 2007), and decreased after 2009
      (5.7% in 2011), the prevalence at the maternity unit remained constant. Between
      2006 and 2009, preterm birth was almost 1.4 times higher in the national
      statistics (using the national or the catchment region samples) than in the
      maternity unit, but no differences were found for low birthweight. CONCLUSION:
      Portuguese preterm birth prevalence seems biased between 2006 and 2009,
      suggesting that early term babies were misclassified as preterm. As civil
      registration systems are important to support public health decisions, monitoring
      strategies should be taken to assure good quality data.

PMID- 26291050
TI  - Prevalence of drug resistance mutations in HAART patients infected with HIV-1
      CRF06_cpx in Estonia.
AB  - HIV-1 drug resistance mutations (DRMs) and substitutions were assessed after the
      failure of the first line non-nucleoside reverse transcriptase inhibitors
      (NNRTIs) + 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)
      treatment regimens (efavirenz [EFV] + lamivudine[3TC] + zidovudine [ZDV] vs. EFV
      + 3TC + ddI) among the HIV-1 CRF06_cpx infected subjects in Estonia. HIV-1
      genomic RNA was sequenced; DRMs and amino acid substitutions were compared in 44
      treatment naive and 45 first-line NNRTI + 2 NRTI treatment failed patients
      consisting of EFV + 3TC + ZDV (n = 17) and EFV + 3TC + didanosine[ddI] (n = 21)
      therapy failed sub-populations. At least one DRM was found in 78% of treatment
      experienced patients. The most common NRTI mutations were M184V (80%), L74V
      (31%), L74I (17%), K219E (9%), and M184I (9%), NNRTI mutations were K103N (83%),
      P225H (14%), L100I (11%), and Y188L (11%), reflecting generally the similar
      pattern of DRMs to that seen in treatment failed subtype B viruses. Sub
      population analysis revealed that EFV + 3TC + ddI failed patients had more DRMs
      compared to EFV + 3TC + ZDV failed patients, especially the ddI DRM L74IV and
      several additional NNRTI DRMs. Additionally, CRF06_cpx specific mutation E179V
      and substitutions R32K, K122E, and V200AE were also detected in treatment
      experienced population. After the failure of the first-line EFV + 3TC + ddI
      therapy HIV-1 CRF06_cpx viruses develop additional NRTI and NNRTI mutations
      compared to EFV + 3TC + ZDV regimen. Therefore the usage of EFV + 3TC + ddI in
      this subtype decreases the options for next regimens containing abacavir, and
      NNRTI class agents.

PMID- 26291051
TI  - Effects of Common Data Errors in Electronic Health Records on Emergency
      Department Operational Performance Metrics: A Monte Carlo Simulation.
AB  - OBJECTIVES: The objective was to estimate how data errors in electronic health
      records (EHRs) can affect the accuracy of common emergency department (ED)
      operational performance metrics. METHODS: Using a 3-month, 7,348-visit data set
      of electronic time stamps from a suburban academic ED as a baseline, Monte Carlo
      simulation was used to introduce four types of data errors (substitution,
      missing, random, and systematic bias) at three frequency levels (2, 4, and 7%).
      Three commonly used ED operational metrics (arrival to clinician evaluation,
      disposition decision to exit for admitted patients, and ED length of stay for
      admitted patients) were calculated and the proportion of ED visits that achieved
      each performance goal was determined. RESULTS: Even small data errors have
      measurable effects on a clinical organization's ability to accurately determine
      whether it is meeting its operational performance goals. Systematic substitution
      errors, increased frequency of errors, and the use of shorter-duration metrics
      resulted in a lower proportion of ED visits reported as meeting the associated
      performance objectives. However, the presence of other error types mitigated
      somewhat the effect of the systematic substitution error. Longer time-duration
      metrics were found to be less sensitive to data errors than shorter time-duration
      metrics. CONCLUSIONS: Infrequent and small-magnitude data errors in EHR time
      stamps can compromise a clinical organization's ability to determine accurately
      if it is meeting performance goals. By understanding the types and frequencies of
      data errors in an organization's EHR, organizational leaders can use data
      management best practices to better measure true performance and enhance
      operational decision-making.

PMID- 26291052
TI  - Dog erythrocyte antigen 1: mode of inheritance and initial characterization.
AB  - BACKGROUND: The dog erythrocyte antigen (DEA) 1 blood group system remains poorly
      defined. OBJECTIVES: The purpose of the study was to determine the DEA 1 mode of
      inheritance and to characterize the DEA 1 antigen and alloantibodies. ANIMALS:
      Canine research colony families, clinic canine patients, and DEA 1.2+ blood bank
      dogs were studied. METHODS: Canine blood was typed by flow cytometry and
      immunochromatographic strips using anti-DEA 1 monoclonal antibodies. Gel column
      experiments with polyclonal and immunoblotting with monoclonal anti-DEA 1
      antibodies were performed to analyze select samples. Cross-reactivity of human
      typing reagents against canine RBC and one monoclonal anti-DEA 1 antibody against
      human RBC panels was assessed. RESULTS: Typing of 12 families comprising 144 dogs
      indicated an autosomal dominant inheritance with >= 4 alleles: DEA 1- (0) and DEA
      1+ weak (1+), intermediate (2+), and strong (3+ and 4+). Samples from 6 dogs
      previously typed as DEA 1.2+ were typed as DEA 1+ or DEA 1- using monoclonal
      antibodies. Human typing reagents produced varied reactions in tube agglutination
      experiments against DEA 1+ and DEA 1- RBC. Polypeptide bands were not detected on
      immunoblots using a monoclonal anti-DEA 1 antibody, therefore the anti-DEA 1
      antibody may be specific for conformational epitopes lost during processing.
      CONCLUSIONS: The autosomal dominant inheritance of DEA 1 with >= 4 alleles
      indicates a complex blood group system; the antigenicity of each DEA 1+ type will
      need to be determined. The biochemical nature of the DEA 1 antigen(s) appears
      different from human blood group systems tested.

PMID- 26291053
TI  - IGF-IR: a new prognostic biomarker for human glioblastoma.
AB  - BACKGROUND: Glioblastomas (GBMs) are the most common malignant primary brain
      tumours in adults and are refractory to conventional therapy, including surgical
      resection, radiotherapy and chemotherapy. The insulin-like growth factor (IGF)
      system is a complex network that includes ligands (IGFI and IGFII), receptors
      (IGF-IR and IGF-IIR) and high-affinity binding proteins (IGFBP-1 to IGFBP-6).
      Many studies have reported a role for the IGF system in the regulation of tumour
      cell biology. However, the role of this system remains unclear in GBMs. METHODS:
      We investigate the prognostic value of both the IGF ligands' and receptors'
      expression in a cohort of human GBMs. Tissue microarray and image analysis were
      conducted to quantitatively analyse the immunohistochemical expression of these
      proteins in 218 human GBMs. RESULTS: Both IGF-IR and IGF-IIR were overexpressed
      in GBMs compared with normal brain (P<10(-4) and P=0.002, respectively).
      Moreover, with regard to standard clinical factors, IGF-IR positivity was
      identified as an independent prognostic factor associated with shorter survival
      (P=0.016) and was associated with a less favourable response to temozolomide.
      CONCLUSIONS: This study suggests that IGF-IR could be an interesting target for
      GBM therapy.

PMID- 26291054
TI  - Coffee, tea, caffeine intake, and the risk of cancer in the PLCO cohort.
AB  - BACKGROUND: The association between coffee intake, tea intake and cancer has been
      extensively studied, but associations are not established for many cancers.
      Previous studies are not consistent on whether caffeine may be the source of
      possible associations between coffee and cancer risk. METHODS: In the Prostate,
      Lung, Colorectal, and Ovarian cancer screening trial, of the 97,334 eligible
      individuals, 10,399 developed cancer. Cancers included were 145 head and neck, 99
      oesophageal, 136 stomach, 1137 lung, 1703 breast, 257 endometrial, 162 ovarian,
      3037 prostate, 318 kidney, 398 bladder, 103 gliomas, and 106 thyroid. RESULTS:
      Mean coffee intake was higher in lower education groups, among current smokers,
      among heavier and longer duration smokers, and among heavier alcohol drinkers.
      Coffee intake was not associated with the risk of all cancers combined (RR=1.00,
      95% confidence interval (CI)=0.96-1.05), whereas tea drinking was associated with
      a decreased risk of cancer overall (RR=0.95, 95% CI=0.94-0.96 for 1+ cups per day
      vs <1 cup per day). For endometrial cancer, a decreased risk was observed for
      coffee intake (RR=0.69, 95% CI=0,52-0.91 for ?2 cups per day). Caffeine intake
      was not associated with cancer risk in a dose-response manner. CONCLUSIONS: We
      observed a decreased risk of endometrial cancer for coffee intake, and a
      decreased risk of cancer overall with tea intake.

PMID- 26291055
TI  - Caspase-8 expression is predictive of tumour response to death receptor 5 agonist
      antibody in Ewing's sarcoma.
AB  - BACKGROUND: Despite good initial response to chemotherapy, 30% of Ewing's sarcoma
      (EWS) patients with localised tumours develop recurrent disease, associated with
      poor prognosis. The aim of this study was to address this challenge by conducting
      preclinical evaluation of a death receptor targeted agent in vitro and in vivo,
      and by identifying predictive biomarkers. METHODS: Cell viability assays, drug
      dose responses, immunoblots, rescue with gene transfer, mice tumour models, and
      statistical comparisons of tumour growth and Kaplan-Meier survival curves.
      RESULTS: This study shows that many EWS cell lines are selectively sensitive to a
      death receptor DR5 antibody and are more resistant to a DR4 antibody. Preclinical
      evaluation of these cell lines indicates their sensitivity to human DR5 agonist
      antibody conatumumab in vitro, which induces rapid activation of caspase-8 and
      apoptosis. We also found that sensitivity to conatumumab correlates with
      expression of caspase-8. Furthermore, the catalytic activity of caspase-8 is both
      necessary and sufficient to confer this sensitivity. In vivo, conatumumab is
      active against an EWS cell line and a patient-derived xenograft with higher
      caspase-8 expression, but is not effective against another with lower caspase-8
      expression. CONCLUSIONS: These studies suggest the potential of conatumumab as a
      therapeutic agent against EWS and caspase-8 as a predictive biomarker for
      sensitivity.

PMID- 26291056
TI  - TAK1-regulated expression of BIRC3 predicts resistance to preoperative
      chemoradiotherapy in oesophageal adenocarcinoma patients.
AB  - BACKGROUND: About 20% of resectable oesophageal carcinoma is resistant to
      preoperative chemoradiotherapy. Here we hypothesised that the expression of the
      antiapoptotic gene Baculoviral inhibitor of apoptosis repeat containing (BIRC)3
      induced by the transforming growth factor beta activated kinase 1 (TAK1) might be
      responsible for the resistance to the proapoptotic effect of chemoradiotherapy in
      oesophageal carcinoma. METHODS: TAK1 kinase activity was inhibited in FLO-1 and
      KYAE-1 oesophageal adenocarcinoma cells using (5Z)-7-oxozeaenol. The BIRC3 mRNA
      expression was measured by qRT-PCR in 65 pretreatment frozen biopsies from
      patients receiving preoperatively docetaxel, cisplatin, 5-fluorouracil, and
      concurrent radiotherapy. Receiver operator characteristic (ROC) analyses were
      performed to determine the performance of BIRC3 expression levels in
      distinguishing patients with sensitive or resistant carcinoma. RESULTS: In vitro,
      (5Z)-7-oxozeaenol significantly reduced BIRC3 expression in FLO-1 and KYAE-1
      cells. Exposure to chemotherapeutic agents or radiotherapy plus (5Z)-7-oxozeaenol
      resulted in a strong synergistic antiapoptotic effect. In patients, median
      expression of BIRC3 was significantly (P<0.0001) higher in adenocarcinoma than in
      the more sensitive squamous cell carcinoma subtype. The BIRC3 expression
      significantly discriminated patients with sensitive or resistant adenocarcinoma
      (AUC-ROC=0.7773 and 0.8074 by size-based pathological response or Mandard's
      tumour regression grade classifications, respectively). CONCLUSIONS: The BIRC3
      expression might be a valid biomarker for predicting patients with oesophageal
      adenocarcinoma that could most likely benefit from preoperative
      chemoradiotherapy.

PMID- 26291057
TI  - Phase I and pharmacological study of pazopanib in combination with oral topotecan
      in patients with advanced solid tumours.
AB  - BACKGROUND: This phase I study evaluated the safety, tolerability, maximum
      tolerated dose (MTD) and pharmacokinetics of two dosing schedules of oral
      topotecan in combination with pazopanib in patients with advanced solid tumours.
      METHODS: Stage I of this study was to determine whether there was an impact of
      pazopanib on topotecan exposure. In stage II, the MTD and safety profile of oral
      topotecan given weekly on days 1, 8 and 15 in a 28-day cycle; or daily-times-five
      on days 1-5 in a 21-day cycle, both in combination with daily pazopanib, were
      explored. RESULTS: In total, 67 patients were enroled. Pazopanib co
      administration caused a substantial increase in exposure to total topotecan (1.7
      fold) compared with topotecan alone, which is considered clinically relevant.
      Topotecan had no effect on pazopanib concentrations. Safety findings were
      consistent with the known profile of both agents. There were three drug-related
      deaths, liver failure, tumour haemorrhage and myelosuppression. Two patients
      experienced dose-limiting toxicities (DLTs; hand-foot syndrome, myelosuppression
      and diarrhoea) on the weekly topotecan schedule and four patients experienced
      DLTs (myelosuppression) on the daily-times-five topotecan schedule. When combined
      with pazopanib, 800 mg daily, the recommended doses for oral topotecan are: 8 mg
      weekly and 2.5 mg daily-times-five. Seven of eight patients with partial response
      had platinum-resistant ovarian cancer. In addition, 54% of patients had stable
      disease with 22% stable for 6 months. CONCLUSIONS: Total topotecan exposure is
      1.7-fold higher when co-administered with pazopanib. Both schedules of
      administration were tolerated and would permit further evaluation, especially the
      weekly schedule.

PMID- 26291060
TI  - Direct transformation of esters into arenes with 1,5-bifunctional organomagnesium
      reagents.
AB  - A direct transformation of carboxylic acid esters into arenes with 1,5
      bifunctional organomagnesium reagents is described. This efficient and practical
      method enables the one-step defunctionalization of various carboxylic acid esters
      to prepare benzene, anthracene, tetracene, and pentacene derivatives. A double
      nucleophilic addition of the 1,5-organodimagnesium reagent to the ester is
      followed by an immediate 1,4-elimination reaction that leads to the direct [5+1]
      formation of a new aromatic ring. 

PMID- 26291058
TI  - WISP-2 in human gastric cancer and its potential metastatic suppressor role in
      gastric cancer cells mediated by JNK and PLC-gamma pathways.
AB  - BACKGROUND: It has recently been shown that WISP proteins (Wnt-inducted secreted
      proteins), a group of intra- and extra-cellular regulatory proteins, have been
      implicated in the initiation and progression of a variety of tumour types
      including colorectal and breast cancer. However, the role of WISP proteins in
      gastric cancer (GC) cells and their clinical implications have not yet been
      elucidated. METHODS: The expression of WISP molecules in a cohort of GC patients
      was analysed using real-time quantitative PCR and immunohistochemistry. The
      expression of a panel of recognised epithelial-mesenchymal transition (EMT)
      markers was quantified using Q-PCR in paired tumour and normal tissues. WISP-2
      knockdown (kd) sublines using ribozyme transgenes were created in the GC cell
      lines AGS and HGC27. Subsequently, several biological functions, including cell
      growth, adhesion, migration and invasion, were studied. Potential pathways for
      the interaction of EMT, extracellular matrix and MMP were evaluated. RESULTS:
      Overexpression of WISP-2 was detected in GC and significantly correlated with
      early tumour node-metastasis staging, differentiation status and positively
      correlated with overall survival and disease-free survival of the patients. WISP
      2 expression was inversely correlated with that of Twist and Slug in paired
      samples. Kd of WISP-2 expression promoted the proliferation, migration and
      invasion of GC cells. WISP-2 suppressed GC cell metastasis through reversing EMT
      and suppressing the expression and activity of MMP9 and MMP2 via JNK and ERK.
      Cell motility analysis indicated that WISP-2 kd contributed to GC cells' motility
      and can be attenuated by PLC-gamma and JNK small inhibitors. CONCLUSIONS:
      Increased expression of WISP-2 in GC is positively correlated with favourable
      clinical features and the survival of patients with GC and is a negative
      regulator of growth, migration and invasion in GC cells. These findings suggest
      that WISP-2 is a potential tumour suppressor in GC.

PMID- 26291059
TI  - Reducing overdiagnosis by polygenic risk-stratified screening: findings from the
      Finnish section of the ERSPC.
AB  - BACKGROUND: We derived estimates of overdiagnosis by polygenic risk groups and
      examined whether polygenic risk-stratified screening for prostate cancer reduces
      overdiagnosis. METHODS: We calculated the polygenic risk score based on genotypes
      of 66 known prostate cancer loci for 4967 men from the Finnish section of the
      European Randomised Study of Screening for Prostate Cancer. We stratified the 72
      072 men in the trial into those with polygenic risk below and above the median.
      Using a maximum likelihood method based on interval cancers, we estimated the
      mean sojourn time (MST) and episode sensitivity. For each polygenic risk group,
      we estimated the proportion of screen-detected cancers that are likely to be
      overdiagnosed from the difference between the observed and expected number of
      screen-detected cancers. RESULTS: Of the prostate cancers, 74% occurred among men
      with polygenic risk above population median. The sensitivity was 0.55 (95%
      confidence interval (CI) 0.45-0.65) and MST 6.3 (95% CI 4.2-8.3) years. The
      overall overdiagnosis was 42% (95% CI 37-52) of the screen-detected cancers, with
      58% (95% CI 54-65) in men with the lower and 37% (95% CI 31-47) in those with
      higher polygenic risk. CONCLUSION: Targeting screening to men at higher polygenic
      risk could reduce the proportion of cancers overdiagnosed.

PMID- 26291061
TI  - Post-weaning environmental enrichment improves BDNF response of adult male rats.
AB  - The environment could have long lasting effects on the individual phenotype
      through developmental plasticity. Early environmental enrichment exerts profound
      biological effects, most of which are quite beneficial ones. To explore the
      enduring effects of rearing condition quality on BDNF(1) responses, we reared
      male Wistar rats from weaning to young-adulthood in three different environmental
      conditions: 1. Enriched 2. Standard, and 3. Isolated. Then, at the age of 16
      weeks, 10 rats from each group were randomly chosen and allocated to six common
      mix cages. They were kept together for 14 weeks. At the end of the experiment,
      each rat received ten inescapable foot-shocks. Twelve hours later, the BDNF
      contents of the amygdala and CA1 sub-region of the dorsal hippocampus were
      measured. The serum BDNF levels, hematocrit values as well as brain and testis
      weights were also measured. Results showed that the environmental enrichment led
      to stronger dorsal hippocampal BDNF response and higher serum BDNF levels, while
      rats from standard laboratory condition showed higher amygdala BDNF response.
      Also, enriched animals showed higher brain weight compared to isolation reared
      rats as well as higher testis weight and hematocrit value compared to animals
      reared in standard laboratory condition. Rats showed less body weights in
      isolated condition. In conclusion, the BDNF profile of enriched animals might
      represent the neurobiological correlate of resilience phenotype under a stressful
      situation. 

PMID- 26291063
TI  - Engineering Gyroid-Structured Functional Materials via Templates Discovered in
      Nature and in the Lab.
AB  - In search of optimal structures for functional materials fabrication, the gyroid
      (G) structure has emerged as a promising subject of widespread research due to
      its distinct symmetry, 3D interconnected networks, and inherent chiral helices.
      In the past two decades, researchers have made great progress fabricating G
      structured functional materials (GSFMs) based on G templates discovered both in
      nature and in the lab. The GSFMs demonstrate extraordinary resonance when
      interacting with light and matter. The superior properties of GSFMs can be
      divided into two categories based on the dominant structural properties, namely,
      dramatic optical performances dominated by short-range symmetry and well-defined
      texture, and effective matter transport due to long-range 3D interconnections and
      high integrity. In this review, G templates suitable for fabrication of GSFMs are
      summarized and classified. State-of-the-art optical applications of GSFMs,
      including photonic bandgap materials, chiral devices, plasmonic materials, and
      matamaterials, are systematically discussed. Applications of GSFMs involved in
      effective electron transport and mass transport, including electronic devices,
      ultrafiltration, and catalysis, are highlighted. Existing challenges that may
      hinder the final application of GSFMS together with possible solutions are also
      presented. 

PMID- 26291062
TI  - Development and comparison of four methods for the extraction of antibiotics from
      a vegetative matrix.
AB  - Studies have shown the potential for antibiotic uptake into food crops from
      irrigation water and soils containing pharmaceuticals. The objective of the
      present study was to develop and compare methods quantifying uptake of
      antibiotics in food crops. Four methods were evaluated: freeze-and-thaw cell
      lysing, mechanical maceration, tissue sonication, and microwave-assisted solvent
      extraction. Four antibiotics (ciprofloxacin, lincomycin, oxytetracycline, and
      sulfamethoxazole) were tested representing 4 classes of antibiotics. The methods
      were evaluated based on method detection limits, analyte recoveries, and sample
      preparation time. The 2 most viable methods, freeze-and-thaw lysing and
      mechanical maceration, were used on replicate lettuce (Lactuca sativa) samples
      grown using irrigation water spiked with 3 of the antibiotic contaminants. Only
      lincomycin and sulfamethoxazole were detected in lettuce samples at
      concentrations as high as 1757 ng/g and 425 ng/g, with detection limits of 57
      ng/g and 35 ng/g, respectively. Freeze-and-thaw cell lysing provided the highest
      level of extraction efficiency on environmental samples and required the least
      amount of sample preparation while providing adequate detection limits and
      reproducible analyte recovery.

PMID- 26291064
TI  - Finding balance: Virus populations reach equilibrium during the infection
      process.
AB  - Virus populations, mixtures of viral strains or species, are a common feature of
      viral infection, and influence many viral processes including infection,
      transmission, and the induction of disease. Yet, little is known of the rules
      that define the composition and structure of these populations. In this study, we
      used three distinct strains of Citrus tristeza virus (CTV) to examine the effect
      of inoculum composition, titer, and order, on the virus population. We found that
      CTV populations stabilized at the same equilibrium irrespective of how that
      population was introduced into a host. In addition, both field and experimental
      observations showed that these equilibria were relatively uniform between
      individual hosts of the same species and under the same conditions. We observed
      that the structure of the equilibria reached is determined primarily by the host,
      with the same inoculum reaching different equilibria in different species, and by
      the fitness of individual virus variants. 

PMID- 26291066
TI  - High aspect ratio, processable coordination polymer gel nanotubes based on an AIE
      active LMWG with tunable emission.
AB  - A new TPE based low molecular weight gelator (LMWG) which displays both AIE and
      MCIE phenomena in gel state has been synthesized. LMWG self-assembles to form 1D
      nanofibers which undergo morphology transformation to coordination polymer gel
      (CPG) nanotubes upon metal ion coordination. CPG shows enhanced mechanical
      stability along with tunable emission properties. 

PMID- 26291065
TI  - Optimization of a multiplex CRISPR/Cas system for use as an antiviral
      therapeutic.
AB  - RNA-guided endonucleases or CRISPR/Cas systems have been widely employed for gene
      engineering/DNA editing applications, and have recently been used against a
      variety of dsDNA viruses as a potential therapeutic. However, in vivo delivery to
      specific tissue reservoirs using adeno-associated virus (AAV) vectors is
      problematic due to the large coding requirement for the principal effector
      commonly used in these applications, Streptococcus pyogenes (Spy) Cas9. Here we
      describe design of a minimal CRISPR/Cas system that is capable of multiplexing
      and can be packaged into a single AAV vector. This system consists of the small
      Type II Cas9 protein from Staphylococcus aureus (Sau) driven by a truncated CMV
      promoter/enhancer, and flanked 3' by a poly(A) addition signal, as well as two
      sgRNA expression cassettes driven by either U6 or ~70-bp tRNA-derived Pol III
      promoters. Specific protocols for construction of these AAV vector scaffolds,
      shuttle cloning of their contents into AAV and lentiviral backbones, and a
      quantitative luciferase assay capable of screening for optimal sgRNAs, are
      detailed. These protocols can facilitate construction of AAV vectors that have
      optimal multiplexed sgRNA expression and function. These will have potential
      utility in multiplex applications, including in antiviral therapy in tissues
      chronically infected with a pathogenic DNA virus.

PMID- 26291067
TI  - Duodenal Expression of 25 Hydroxyvitamin D3-1alpha-hydroxylase Is Higher in
      Adolescents Than in Children and Adults.
AB  - CONTEXT: Puberty is associated with increased dietary calcium absorption.
      However, little is known about the metabolic adaptations that enhance calcium
      absorption during puberty. OBJECTIVES: To investigate duodenal 25-hydroxy vitamin
      D-1alpha-hydroxylase (CYP 27B1) mRNA expression and duodenal 1,25
      dihydroxyvitamin D3 (1,25(OH)2D3) production in children, adolescents, and
      adults. DESIGN AND METHODS: CYP27B1a nd IGF1 mRNA expression and 1,25(OH)2D3
      production were determined in duodenal biopsies. CYP27B1 expression was also
      determined after IGF1R inhibitor treatment of human and mice duodenal explants.
      mRNA expression was determined by RT-PCR, and CYP27B1 activity was determined by
      incubating duodenal explants with 25(OH)D3 and measuring 1,25(OH)2D3 production
      by radioimmunoassay. RESULTS: CYP27B1 mRNA expression was 13.7 and 10.4 times
      higher in biopsies from adolescents compared to adults and children,
      respectively. IGF1 mRNA expression was 30% and 45% higher in explants from
      adolescents and children, respectively, compared to adults. Inhibition of IGF1
      receptor activity decreased CYP27B1 expression in explants from both mice (85%)
      and humans (24%). 1,25(OH)2D3 production reached a maximum velocity of 768 +/-
      268 pmol/l/mg protein at 748.8 nmol/l of 25(OH)D3 in children and adolescents,
      whereas the maximum velocity was 86.4 +/- 43.2 pmol/l/mg protein in adults. The
      substrate concentration at which the enzyme shows half of its maximum activity
      was similar in all groups, ranging between 624 and 837 nmol/L of 25(OH)D3.
      CONCLUSIONS: Increased CYP27B1 expression and local duodenal 1,25(OH)2D3
      production during puberty may be a metabolic adaptation that promotes dietary
      calcium absorption. IGF1, a major factor in skeletal growth, is also involved in
      the modulation of CYP27B1 expression in the gut and may increase calcium supply
      for the growing bone.

PMID- 26291068
TI  - Decreased VLDL-Apo B 100 Fractional Synthesis Rate Despite Hypertriglyceridemia
      in Subjects With Type 2 Diabetes and Nephropathy.
AB  - CONTEXT: Subjects with type 2 diabetes mellitus (T2DM) and diabetic nephropathy
      (DN) often exhibit hypertriglyceridemia. The mechanism(s) of such an increase are
      poorly known. OBJECTIVE: We investigated very low-density lipoprotein (VLDL)-Apo
      B 100 kinetics in T2DM subjects with and without DN, and in healthy controls.
      DESIGN: Stable isotope (13)C-leucine infusion and modeling analysis of tracer-to
      tracee ratio dynamics in the protein product pool in the 6-8-h period following
      tracer infusion were employed. SETTING: Male subjects affected by T2DM, either
      with (n = 9) or without (n = 5) DN, and healthy male controls (n = 6), were
      studied under spontaneous glycemic levels in the post-absorptive state. RESULTS:
      In the T2DM patients with DN, plasma triglyceride (TG) (mean +/- SD; 2.2 +/- 0.8
      mmol/L) and VLDL-Apo B 100 (17.4 +/- 10.4 mg/dL) concentrations, and VLDL-Apo B
      100 pool (0.56 +/- 0.29 g), were ~60-80% greater (P < .05 or less) than those of
      the T2DM subjects without DN (TG, 1.4 +/- 0.5 mmol/L; VLDL-Apo B 100, 9.9 +/- 2.5
      mg/dL; VLDL-Apo B 100 pool, 0.36 +/- 0.09 g), and ~80-110% greater (P < .04 or
      less) than those of nondiabetic controls (TG, 1.2 +/- 0.4 mmol/L; VLDL-Apo B 100,
      8.2 +/- 1.7 mg/dL; VLDL-Apo B 100, 0.32 +/- 0.09 g). In sharp contrast however,
      in the subjects with T2DM and DN, VLDL-Apo B 100 fractional synthesis rate was
      >=50% lower (4.8 +/- 2.2 pools/d) than that of either the T2DM subjects without
      DN (9.9 +/- 4.3 pools/d; P < .025) or the control subjects (12.5 +/- 9.1 pools/d;
      P < .04). CONCLUSIONS: The hypertriglyceridemia of T2DM patients with DN is not
      due to hepatic VLDL-Apo B 100 overproduction, which is decreased, but it should
      be attributed to decreased apolipoprotein removal.

PMID- 26291069
TI  - Contact transfer length investigation of a 2D nanoparticle network by scanning
      probe microscopy.
AB  - Nanoparticle network devices find growing application in sensing and electronics.
      One recurring challenge in the design and fabrication of this class of devices is
      ensuring a stable interface via robust yet unobstructive electrodes. A figure of
      merit which dictates the minimum electrode overlap required for optimal charge
      injection into the network is the contact transfer length. However, we find that
      traditional contact characterization using the transmission line model, an
      indirect method which requires extrapolation, is insufficient for network
      devices. Instead, we apply Kelvin probe force microscopy to characterize the
      contact resistance by imaging the surface potential with nanometer resolution. We
      then use scanning probe lithography to directly investigate the contact transfer
      length. We have determined the transfer length in graphene contacted devices to
      be 200-400 nm, thus apt for further device reduction which is often necessary for
      on-site sensing applications. Simulations from a two-dimensional resistor model
      support our observations and are expected to be an important tool for further
      optimizing the design of nanoparticle-based devices. 

PMID- 26291070
TI  - Chlorotoxin-Conjugated Multifunctional Dendrimers Labeled with Radionuclide 131I
      for Single Photon Emission Computed Tomography Imaging and Radiotherapy of
      Gliomas.
AB  - Chlorotoxin-conjugated multifunctional dendrimers labeled with radionuclide 131I
      were synthesized and utilized for targeted single photon emission computed
      tomography (SPECT) imaging and radiotherapy of cancer. In this study, generation
      five amine-terminated poly(amidoamine) dendrimers were used as a platform to be
      sequentially conjugated with polyethylene glycol (PEG), targeting agent
      chlorotoxin (CTX), and 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO). This was
      followed by acetylation of the remaining dendrimer terminal amines and
      radiolabeling with 131I to form the targeted theranostic dendrimeric
      nanoplatform. We show that the dendrimer platform possessing approximately 7.7
      CTX and 21.1 HPAO moieties on each dendrimer displays excellent cytocompatibility
      in a given concentration range (0-20 MUM) and can specifically target cancer
      cells overexpressing matrix metallopeptidase 2 (MMP2) due to the attached CTX.
      With the attached HPAO moiety having the phenol group, the dendrimer platform can
      be effectively labeled with radioactive 131I with good stability and high
      radiochemical purity. Importantly, the 131I labeling renders the dendrimer
      platform with an ability to be used for targeted SPECT imaging and radiotherapy
      of an MMP2-overexpressing glioma model in vivo. The developed radiolabeled
      multifunctional dendrimeric nanoplatform may hold great promise to be used for
      targeted theranostics of human gliomas.

PMID- 26291071
TI  - Bifidobacterium breve Sepsis in Child with High-Risk Acute Lymphoblastic
      Leukemia.

PMID- 26291072
TI  - Spatial distributions of local illumination color in natural scenes.
AB  - In natural complex environments, the elevation of the sun and the presence of
      occluding objects and mutual reflections cause variations in the spectral
      composition of the local illumination across time and location. Unlike the
      changes in time and their consequences for color appearance and constancy, the
      spatial variations of local illumination color in natural scenes have received
      relatively little attention. The aim of the present work was to characterize
      these spatial variations by spectral imaging. Hyperspectral radiance images were
      obtained from 30 rural and urban scenes in which neutral probe spheres were
      embedded. The spectra of the local illumination at 17 sample points on each
      sphere in each scene were extracted and a total of 1904 chromaticity coordinates
      and correlated color temperatures (CCTs) derived. Maximum differences in
      chromaticities over spheres and over scenes were similar. When data were pooled
      over scenes, CCTs ranged from 3000 K to 20,000 K, a variation of the same order
      of magnitude as that occurring over the day. Any mechanisms that underlie stable
      surface color perception in natural scenes need to accommodate these large
      spatial variations in local illumination color.

PMID- 26291073
TI  - Human perception of visual stimuli modulated by direction of linear polarization.
AB  - This study explores both theoretically and experimentally the human perception of
      polarized light beyond that currently established. The radial analyser theory of
      Haidinger's phenomenon (HP) is used to predict the effect of observing visual
      stimuli comprising patterned zones characterized by orthogonal planes of linear
      polarization (linear polarization direction fields, LPD-fields). Any pattern can
      be represented as an LPD-field including optotypes and geometric forms. Simulated
      percepts differ from the original patterns although edges are mostly preserved.
      In edge-rich images a cross of attenuating contrast spanning the field of view is
      predicted. The mathematical model is verified experimentally using a liquid
      crystal display (LCD)-based polarization modulator imaged through a tangential
      (azimuthal) analyser with properties complementary to a radial analyser. The LCD
      device is then used in vivo to elicit perceptual responses in human subjects.
      Normal humans are found to readily detect spatially and temporally modulated
      isoluminant spatially-isochromatic, highly polarized LPD stimuli. Most subjects
      match the stimuli to corresponding images of theoretically predicted percepts. In
      particular edge perception and the presence of the contrast cross was confirmed.
      Unlike HP, static patterned LPD stimuli are perceived without difficulty. The
      simplest manifestation of human polarization perception is HP which is the
      fundamental element of an open set of stimulus-dependent percepts. This study
      demonstrates that humans have the ability to perceive and identify visual pattern
      stimuli defined solely by polarization state modulation. 

PMID- 26291074
TI  - Use of exotic plants to control Spartina alterniflora invasion and promote
      mangrove restoration.
AB  - In coastal China, the exotic invasive Spartina alterniflora is preventing the
      establishment of native mangroves. The use of exotic species, control of exotic
      plant invasion, and restoration of native plant communities are timely research
      issues. We used exotic Sonneratia apetala Buch.-Ham and S. caseolaris (L.) Engl.
      to control invasive Spartina alterniflora Loisel through replacement control for
      five years, which concurrently promoted the restoration of native mangroves. This
      process includes three stages. I: In a mangrove area invaded by S. alterniflora,
      exotic S. apetala and S. caseolaris grew rapidly due to their relatively fast
      growing character and an allelopathic effect. II: Fast-growing S. apetala and S.
      caseolaris eradicate S. alterniflora through shading and allelopathy. III: The
      growth of native mangrove was promoted because exotic plant seedlings cannot
      regenerate in the understory shade, whereas native mesophytic mangrove plants
      seedlings can grow; when the area experiences extreme low temperatures in winter
      or at other times, S. apetala dies, and native mangrove species grow to restore
      the communities. This model has important implications for addressing the
      worldwide problems of "how to implement the ecological control of invasion using
      exotic species" and "how to concurrently promote native community restoration
      during the control of exotic invasion". 

PMID- 26291075
TI  - Toward an Understanding of the Role of the Environment in the Development of
      Early Callous Behavior.
AB  - Key to understanding the long-term impact of social inequalities is identifying
      early behaviors that may signal higher risk for later poor psychosocial outcomes,
      such as psychopathology. A set of early-emerging characteristics that may signal
      risk for later externalizing psychopathology is callous-unemotional (CU)
      behavior. CU behavior predicts severe and chronic trajectories of externalizing
      behaviors in youth. However, much research on CU behavior has focused on late
      childhood and adolescence, with little attention paid to early childhood when
      preventative interventions may be most effective. In this article, we summarize
      our recent work showing that (a) CU behavior can be identified in early childhood
      using items from common behavior checklists, (b) CU behavior predicts worse
      outcomes across early childhood, (c) CU behavior exhibits a nomological network
      distinct from other early externalizing behaviors, and (d) malleable
      environmental factors, particularly parenting, may play a role in the development
      of early CU behaviors. We discuss the challenges of studying contextual
      contributors to the development of CU behavior in terms of gene-environment
      correlations and present initial results from work examining CU behavior in an
      adoption study in which gene-environment correlations are examined in early
      childhood. We find that parenting is a predictor of early CU behavior even in a
      sample in which parents are not genetically related to the children.

PMID- 26291076
TI  - Minimal feedback to a rhythm generator improves the robustness to slope
      variations of a compass biped.
AB  - In recent years there has been a growing interest in the field of dynamic walking
      and bio-inspired robots. However, while walking and running on a flat surface
      have been studied extensively, walking dynamically over terrains with varying
      slope remains a challenge. Previously we developed an open loop controller based
      on a central pattern generator (CPG). The controller applied predefined torque
      patterns to a compass-gait biped, and achieved stable gaits over a limited range
      of slopes. In this work, this range is greatly extended by applying a once per
      cycle feedback to the CPG controller. The terrain's slope is measured and used to
      modify both the CPG frequency and the torque amplitude once per step. A multi
      objective optimization algorithm was used to tune the controller parameters for a
      simulated CB model. The resulting controller successfully traverses terrains with
      slopes ranging from +7 degrees  to -8 degrees , comparable to most slopes found
      in human constructed environments. Gait stability was verified by computing the
      linearized Poincare Map both numerically and analytically. 

PMID- 26291078
TI  - Natural Killer p46 Controls Hepatitis B Virus Replication and Modulates Liver
      Inflammation.
AB  - Natural killer (NK) cells play an important role in hepatitis B virus (HBV)
      infection control, and are regulated by a complex network of activating and
      inhibitory receptors. However, NK cell activity in HBV patients remains poorly
      understood. The objective of this study was to investigate the phenotypic and
      functional characteristics of circulating NK cells in patients during different
      chronic hepatitis B (CHB) infection stages. We investigated NK cell phenotypes,
      receptor expression and function in 86 CHB patients and 20 healthy controls. NK
      cells were purified and NK cell subsets were characterized by flow cytometry.
      Cytotoxic activity (CD107a) and interferon-gamma (IFN-gamma) secretion were
      examined, and Natural Killer p46 (NKP46) blockade and spontaneous NK cell
      cytolytic activity against K562, HepG2 and HepG2.215 cell lines was studied.
      Activating NKp46 receptor expression was higher in inactive HBsAg carriers when
      compared with other groups (p = 0.008). NKp46 expression negatively correlated
      with HBV DNA (R = -0.253, p = 0.049) and ALT (R = -0.256, p = 0.045) levels.
      CD107a was higher in immune-activated groups when compared with immune-tolerant
      groups (p = 0.039). CD107a expression was related to viral load (p = 0.02) and
      HBeAg status (p = 0.024). In vitro NKp46 blockade reduced NK cell cytolytic
      activity against HepG2 and HepG2.215 cell lines (p = 0.02; p = 0.039).
      Furthermore, NK cells from high viral load CHB patients displayed significantly
      lower specific cytolytic activity against anti-NKp46-loaded K562 targets (p =
      0.0321). No significant differences were observed in IFN-gamma secretion (p >
      0.05). In conclusion, NKp46 expression regulates NK cell cytolytic function.
      NKp46 may moderate NK cell activity during HBV replication suppression and HBV
      associated liver damage and may be critical for NK cell activity during CHB
      infection. 

PMID- 26291077
TI  - The Drosophila bag of marbles Gene Interacts Genetically with Wolbachia and Shows
      Female-Specific Effects of Divergence.
AB  - Many reproductive proteins from diverse taxa evolve rapidly and adaptively. These
      proteins are typically involved in late stages of reproduction such as sperm
      development and fertilization, and are more often functional in males than
      females. Surprisingly, many germline stem cell (GSC) regulatory genes, which are
      essential for the earliest stages of reproduction, also evolve adaptively in
      Drosophila. One example is the bag of marbles (bam) gene, which is required for
      GSC differentiation and germline cyst development in females and for regulating
      mitotic divisions and entry to spermatocyte differentiation in males. Here we
      show that the extensive divergence of bam between Drosophila melanogaster and D.
      simulans affects bam function in females but has no apparent effect in males. We
      further find that infection with Wolbachia pipientis, an endosymbiotic bacterium
      that can affect host reproduction through various mechanisms, partially
      suppresses female sterility caused by bam mutations in D. melanogaster and
      interacts differentially with bam orthologs from D. melanogaster and D. simulans.
      We propose that the adaptive evolution of bam has been driven at least in part by
      the long-term interactions between Drosophila species and Wolbachia. More
      generally, we suggest that microbial infections of the germline may explain the
      unexpected pattern of evolution of several GSC regulatory genes. 

PMID- 26291079
TI  - Digital Photoplethysmography for Assessment of Arterial Stiffness: Repeatability
      and Comparison with Applanation Tonometry.
AB  - INTRODUCTION: Arterial stiffness is an independent risk factor for cardiovascular
      morbidity and can be assessed by applanation tonometry by measuring pulse wave
      velocity (PWV) and augmentation index (AIX) by pressure pulse wave analysis
      (PWA). As an inexpensive and operator independent alternative, photoelectric
      plethysmography (PPG) has been introduced with analysis of the digital volume
      pulse wave (DPA) and its second derivatives of wave reflections. OBJECTIVE: The
      objective was to investigate the repeatability of arterial stiffness parameters
      measured by digital pulse wave analysis (DPA) and the associations to applanation
      tonometry parameters. METHODS AND RESULTS: 112 pregnant and non-pregnant
      individuals of different ages and genders were examined with SphygmoCor arterial
      wall tonometry and Meridian DPA finger photoplethysmography. Coefficients of
      repeatability, Bland-Altman plots, intraclass correlation coefficients and
      correlations to heart rate (HR) and body height were calculated for DPA
      variables, and the DPA variables were compared to tonometry variables left
      ventricular ejection time (LVET), PWV and AIX. No DPA variable showed any
      systematic measurement error or excellent repeatability, but dicrotic index (DI),
      dicrotic dilatation index (DDI), cardiac ejection elasticity index (EEI), aging
      index (AI) and second derivatives of the crude pulse wave curve, b/a and e/a,
      showed good repeatability. Overall, the correlations to AIX were better than to
      PWV, with correlations coefficients >0.70 for EEI, AI and b/a. Considering the
      level of repeatability and the correlations to tonometry, the overall best DPA
      parameters were EEI, AI and b/a. The two pansystolic time parameters, ejection
      time compensated (ETc) by DPA and LVET by tonometry, showed a significant but
      weak correlation. CONCLUSION: For estimation of the LV function, ETc, EEI and b/a
      are suitable, for large artery stiffness EEI, and for small arteries DI and DDI.
      The only global parameter, AI, showed a high repeatability and the overall best
      correlations with AIX and PWV.

PMID- 26291080
TI  - Single Doses up to 800 mg of E-52862 Do Not Prolong the QTc Interval--A
      Retrospective Validation by Pharmacokinetic-Pharmacodynamic Modelling of
      Electrocardiography Data Utilising the Effects of a Meal on QTc to Demonstrate
      ECG Assay Sensitivity.
AB  - BACKGROUND: E-52862 is a Sigma-1 receptor antagonist (S1RA) currently under
      investigation as a potential analgesic medicine. We successfully applied a
      concentration-effect model retrospectively to a four-way crossover Phase I single
      ascending dose study and utilized the QTc shortening effects of a meal to
      demonstrate assay sensitivity by establishing the time course effects from
      baseline in all four periods, independently from any potential drug effects.
      METHODS: Thirty two healthy male and female subjects were included in four
      treatment periods to receive single ascending doses of 500 mg, 600 mg or 800 mg
      of E-52862 or placebo. PK was linear over the dose range investigated and doses
      up to 600 mg were well tolerated. The baseline electrocardiography (ECG)
      measurements on Day-1 were time-matched with ECG and pharmacokinetic (PK) samples
      on Day 1 (dosing day). RESULTS: In this conventional mean change to time-matched
      placebo analysis, the largest time-matched difference to placebo QTcI was 1.44 ms
      (90% CI: -4.04, 6.93 ms) for 500 mg; -0.39 ms (90% CI: -3.91, 3.13 ms) for 600 mg
      and 1.32 ms (90% CI: -1.89, 4.53 ms) for 800 mg of E-52862, thereby showing the
      absence of any QTc prolonging effect at the doses tested. In addition
      concentration-effect models, one based on the placebo corrected change from
      baseline and one for the change of QTcI from average baseline with time as fixed
      effect were fitted to the data confirming the results of the time course
      analysis. CONCLUSION: The sensitivity of this study to detect small changes in
      the QTc interval was confirmed by demonstrating a shortening of QTcF of -8.1 (90%
      CI: -10.4, -5.9) one hour and -7.2 (90% CI: -9.4, -5.0) three hours after a
      standardised meal. TRIAL REGISTRATION: EU Clinical Trials Register EudraCT 2010
      020343 13.

PMID- 26291082
TI  - Prognostic Impact of Tricuspid Regurgitation in Patients Undergoing Aortic Valve
      Surgery for Aortic Stenosis.
AB  - BACKGROUND: The prognostic significance of tricuspid regurgitation (TR) and right
      ventricular (RV) function in patients undergoing aortic valve replacement (AVR)
      for severe aortic stenosis (AS) is unknown. The aim of the present study was to
      evaluate the impact of TR and RV systolic dysfunction on early and late mortality
      in this setting. METHODS: This was a prospective single-center observational
      study. 465 consecutive patients who were referred to AVR for severe AS were
      investigated. Significant TR was defined as TR>=moderate by transthoracic
      echocardiography. RESULTS: At baseline, significant TR was present in 26 (5.6%)
      patients. Patients with TR presented with a higher EuroSCORE I (p = 0.001), a
      higher incidence of previous cardiac surgery (p<0.001), pulmonary hypertension (p
      = 0.003), more dilated RVs (p = 0.001), and more frequent RV dysfunction (p =
      0.001). Patients were followed for an average of 5.2 (+/-2.8 SD) years. By
      multivariable Cox regression analysis TR (p = 0.014), RV dysfunction (p = 0.046),
      age (p = 0.001) and concomitant coronary artery bypass graft surgery (CABG, p =
      0.003) were independently associated with overall mortality. By Kaplan-Meier
      analysis, survival rates were significantly worse in patients with significant
      than with non-significant TR (log rank p = 0.001). CONCLUSIONS: TR, RV
      dysfunction, age, and concomitant CABG are associated with outcome in patients
      undergoing AVR for severe AS. This finding underlines the importance of a
      thorough echocardiographic evaluation with particular consideration of the right
      heart in these patients.

PMID- 26291081
TI  - Virus-Induced Gene Silencing Using Tobacco Rattle Virus as a Tool to Study the
      Interaction between Nicotiana attenuata and Rhizophagus irregularis.
AB  - Most land plants live in a symbiotic association with arbuscular mycorrhizal
      fungi (AMF) that belong to the phylum Glomeromycota. Although a number of plant
      genes involved in the plant-AMF interactions have been identified by analyzing
      mutants, the ability to rapidly manipulate gene expression to study the potential
      functions of new candidate genes remains unrealized. We analyzed changes in gene
      expression of wild tobacco roots (Nicotiana attenuata) after infection with
      mycorrhizal fungi (Rhizophagus irregularis) by serial analysis of gene expression
      (SuperSAGE) combined with next generation sequencing, and established a virus
      induced gene-silencing protocol to study the function of candidate genes in the
      interaction. From 92,434 SuperSAGE Tag sequences, 32,808 (35%) matched with our
      in-house Nicotiana attenuata transcriptome database and 3,698 (4%) matched to
      Rhizophagus genes. In total, 11,194 Tags showed a significant change in
      expression (p<0.05, >2-fold change) after infection. When comparing the functions
      of highly up-regulated annotated Tags in this study with those of two previous
      large-scale gene expression studies, 18 gene functions were found to be up
      regulated in all three studies mainly playing roles related to phytohormone
      metabolism, catabolism and defense. To validate the function of identified
      candidate genes, we used the technique of virus-induced gene silencing (VIGS) to
      silence the expression of three putative N. attenuata genes: germin-like protein,
      indole-3-acetic acid-amido synthetase GH3.9 and, as a proof-of-principle, calcium
      and calmodulin-dependent protein kinase (CCaMK). The silencing of the three plant
      genes in roots was successful, but only CCaMK silencing had a significant effect
      on the interaction with R. irregularis. Interestingly, when a highly activated
      inoculum was used for plant inoculation, the effect of CCaMK silencing on fungal
      colonization was masked, probably due to trans-complementation. This study
      demonstrates that large-scale gene expression studies across different species
      induce of a core set of genes of similar functions. However, additional factors
      seem to influence the overall pattern of gene expression, resulting in high
      variability among independent studies with different hosts. We conclude that VIGS
      is a powerful tool with which to investigate the function of genes involved in
      plant-AMF interactions but that inoculum strength can strongly influence the
      outcome of the interaction. 

PMID- 26291083
TI  - A Re-Interpretation of the 'Two-child Norm' in Post-Transitional Demographic
      Systems: Fertility Intentions in Taiwan.
AB  - Taiwan currently has one of the lowest fertility rates in the world, leading to
      projections of rapid population ageing and decline. In common with other
      territories in Pacific Asia, policies designed to support childbearing have
      recently been introduced. Some optimism for the future success of these policies
      has been drawn from the fact that the 'ideal' number of children stated in
      Taiwanese surveys is over two. In this way, Taiwan appears to fit the 'two-child
      norm' model identified for Europe and North America. Furthermore, this feature
      has led commentators to state that Taiwan is not in a 'low fertility trap'-where
      positive feedback mechanisms emanating from the normalisation of small families,
      slow economic growth and ageing/declining population mean attempts to increase
      fertility become ever less likely to succeed. Using a recent national
      representative survey, and arguing that 'intentions' are a more reliable guide to
      understanding the circumstances of family formation, this paper explores
      fertility intentions in Taiwan with a special focus on women at parity one and
      parity two. This will form the first full-length examination of fertility
      intentions in Taiwan published in English and one of the few studies of Pacific
      Asia that reports a micro-level analysis. We argue that using intentions should
      provide a better 'barometer' of attitudes towards childbearing in Taiwan, and
      that through micro-level analysis, we can better identify the predictors of
      intentions that could, in turn, provide useful clues both for projections as well
      as shaping policy responses. While we found some evidence for a 'two-child norm'
      among childless women, this could be an unrealistic ideal. This is supported by
      the fact that a majority of women with one child do not intend to have another. 

PMID- 26291084
TI  - The Absence of CYP3A5*3 Is a Protective Factor to Anticonvulsants
      Hypersensitivity Reactions: A Case-Control Study in Brazilian Subjects.
AB  - Although aromatic anticonvulsants are usually well tolerated, they can cause
      cutaneous adverse drug reactions in up to 10% of patients. The clinical
      manifestations of the antiepileptics-induced hypersensitivity reactions (AHR)
      vary from mild skin rashes to severe cutaneous drug adverse reactions which are
      related to high mortality and significant morbidity. Genetic polymorphisms in
      cytochrome P450 genes are associated with altered enzymatic activity and may
      contribute to the risk of AHR. Here we present a case-control study in which we
      genotyped SNPs of CYP2C19, 2C9 and 3A5 of 55 individuals with varying severities
      of AHR, 83 tolerant, and 366 healthy control subjects from Sao Paulo, Brazil.
      Clinical characterization was based on standardized scoring systems and drug
      patch test. All in vivo investigation followed the ENDA (European Network of Drug
      Allergy) recommendations. Genotype was determined by real time PCR using
      peripheral blood DNA as a template. Of all 504 subjects, 65% were females, 45%
      self-identified as Afro-American, 38% as Caucasian and 17% as having non-African
      mixed ascendancy. Amongst 55 subjects with AHR, 44 had severe cutaneous drug
      adverse reactions. Of the 46 drug patch tests performed, 29 (63%) were positive.
      We found a strong association between the absence of CYP3A5*3 and tolerant
      subjects when compared to AHR (p = 0.0002, OR = 5.28 [CI95% 2.09-14.84]). None of
      our groups presented positive association with CYP2C19 and 2C9 polymorphisms,
      however, both SNPs contributed to separation of cases and tolerants in a
      Classification and Regression Tree. Our findings indicate that drug metabolism
      genes can contribute in the tolerability of antiepileptics. CYP3A5*3 is the most
      prevalent CYP3A5 allele associated with reduced enzymatic function. The current
      study provides evidence that normal CYP3A5 activity might be a protective factor
      to aromatic antiepileptics-induced hypersensitivity reactions in Brazilian
      subjects. 

PMID- 26291086
TI  - Correction: Zoogeography of South American Forest-Dwelling Bats: Disjunct
      Distributions or Sampling Deficiencies?

PMID- 26291085
TI  - Comprehensive DNA Methylation Analysis Reveals a Common Ten-Gene Methylation
      Signature in Colorectal Adenomas and Carcinomas.
AB  - Microarray analysis of promoter hypermethylation provides insight into the role
      and extent of DNA methylation in the development of colorectal cancer (CRC) and
      may be co-monitored with the appearance of driver mutations. Colonic biopsy
      samples were obtained endoscopically from 10 normal, 23 adenoma (17 low-grade
      (LGD) and 6 high-grade dysplasia (HGD)), and 8 ulcerative colitis (UC) patients
      (4 active and 4 inactive). CRC samples were obtained from 24 patients (17
      primary, 7 metastatic (MCRC)), 7 of them with synchronous LGD. Field effects were
      analyzed in tissues 1 cm (n = 5) and 10 cm (n = 5) from the margin of CRC. Tissue
      materials were studied for DNA methylation status using a 96 gene panel and for
      KRAS and BRAF mutations. Expression levels were assayed using whole genomic mRNA
      arrays. SFRP1 was further examined by immunohistochemistry. HT29 cells were
      treated with 5-aza-2' deoxycytidine to analyze the reversal possibility of DNA
      methylation. More than 85% of tumor samples showed hypermethylation in 10 genes
      (SFRP1, SST, BNC1, MAL, SLIT2, SFRP2, SLIT3, ALDH1A3, TMEFF2, WIF1), whereas the
      frequency of examined mutations were below 25%. These genes distinguished
      precancerous and cancerous lesions from inflamed and healthy tissue. The mRNA
      alterations that might be caused by systematic methylation could be partly
      reversed by demethylation treatment. Systematic changes in methylation patterns
      were observed early in CRC carcinogenesis, occuring in precursor lesions and CRC.
      Thus we conclude that DNA hypermethylation is an early and systematic event in
      colorectal carcinogenesis, and it could be potentially reversed by systematic
      demethylation therapy, but it would need more in vitro and in vivo experiments to
      support this theory. 

PMID- 26291087
TI  - Socioeconomic Status and Foodborne Pathogens in Connecticut, USA, 2000-2011(1).
AB  - Foodborne pathogens cause >9 million illnesses annually. Food safety efforts
      address the entire food chain, but an essential strategy for preventing foodborne
      disease is educating consumers and food preparers. To better understand the
      epidemiology of foodborne disease and to direct prevention efforts, we examined
      incidence of Salmonella infection, Shiga toxin-producing Escherichia coli
      infection, and hemolytic uremic syndrome by census tract-level socioeconomic
      status (SES) in the Connecticut Foodborne Diseases Active Surveillance Network
      site for 2000-2011. Addresses of case-patients were geocoded to census tracts and
      linked to census tract-level SES data. Higher census tract-level SES was
      associated with Shiga toxin-producing Escherichia coli, regardless of serotype;
      hemolytic uremic syndrome; salmonellosis in persons >=5 years of age; and some
      Salmonella serotypes. A reverse association was found for salmonellosis in
      children <5 years of age and for 1 Salmonella serotype. These findings will
      inform education and prevention efforts as well as further research. 

PMID- 26291088
TI  - Engineering covalent loops in proteins can serve as an on/off switch to regulate
      threaded topologies.
AB  - Knots in proteins are under active investigation motivating refinements of
      current techniques and the development of tools to better understand the knotted
      topology. A strong focus is to identify new knots and expand upon the current
      understanding of their complex topology. Previous work has shown that the knotted
      topology, even in the simplest case of knots, encompasses a variety of unique
      challenges in folding and tying a chain. To bypass many of the in vitro
      experimental complications involved in working with knots, it is useful to apply
      methodologies to a more simplified system. The pierced lasso bundles (PLB), we
      discovered where a single disulphide bridge holds the threaded topology together,
      presents a simpler system to study knots in vitro. Having a disulphide bridge as
      an on/off switch between the threaded/unthreaded topology is advantageous because
      a covalent loop allows manipulation of the knot without directly altering
      affecting secondary and tertiary structure. Because disulphide bridges are
      commonly used in protein engineering, a pierced lasso (PL) topology can be easily
      introduced into a protein of interest to form a knotted topology within a given
      secondary structure. It is also important to take into account that if formed,
      disulphides can inadvertently introduce an unwanted PL. This was found upon
      determination of the crystal structure (PDB code 2YHG) of the recently de novo
      designed nucleoside hydrolase. Our detailed investigations of the PL presented
      here will allow researchers to look at the introduction of disulphide bridges in
      a larger context with respect to potential geometrical consequences on the
      structure and functional properties of proteins. 

PMID- 26291089
TI  - Comparative Accuracy of the InBios Scrub Typhus Detect IgM Rapid Test for the
      Detection of IgM Antibodies by Using Conventional Serology.
AB  - This study investigated the comparative accuracy of a recombinant 56-kDa type
      specific antigen-based rapid diagnostic test (RDT) for scrub typhus for the
      detection of IgM antibodies by using conventional serology in well-characterized
      serum samples from undifferentiated febrile illness patients. The RDT showed high
      specificity and promising comparative accuracy, with 82% sensitivity and 98%
      specificity for samples defined positive at an IgM indirect immunofluorescence
      assay positivity cutoff titer of >=1:1,600 versus 92% and 95% at >=1:6,400,
      respectively. 

PMID- 26291091
TI  - Target-induced nano-enzyme reactor mediated hole-trapping for high-throughput
      immunoassay based on a split-type photoelectrochemical detection strategy.
AB  - Photoelectrochemical (PEC) detection is an emerging and promising analytical
      tool. However, its actual application still faces some challenges like potential
      damage of biomolecules (caused by itself system) and intrinsic low-throughput
      detection. To solve the problems, herein we design a novel split-type
      photoelectrochemical immunoassay (STPIA) for ultrasensitive detection of prostate
      specific antigen (PSA). Initially, the immunoreaction was performed on a
      microplate using a secondary antibody/primer-circular DNA-labeled gold
      nanoparticle as the detection tag. Then, numerously repeated oligonucleotide
      sequences with many biotin moieties were in situ synthesized on the nanogold tag
      via RCA reaction. The formed biotin concatamers acted as a powerful scaffold to
      bind with avidin-alkaline phosphatase (ALP) conjugates and construct a nanoenzyme
      reactor. By this means, enzymatic hydrolysate (ascorbic acid) was generated to
      capture the photogenerated holes in the CdS quantum dot-sensitized TiO2 nanotube
      arrays, resulting in amplification of the photocurrent signal. To elaborate, the
      microplate-based immunoassay and the high-throughput detection system, a
      semiautomatic detection cell (installed with a three-electrode system), was
      employed. Under optimal conditions, the photocurrent increased with the
      increasing PSA concentration in a dynamic working range from 0.001 to 3 ng mL(
      1), with a low detection limit (LOD) of 0.32 pg mL(-1). Meanwhile, the developed
      split-type photoelectrochemical immunoassay exhibited high specificity and
      acceptable accuracy for analysis of human serum specimens in comparison with
      referenced electrochemiluminescence immunoassay method. Importantly, the system
      was not only suitable for the sandwich-type immunoassay mode, but also utilized
      for the detection of small molecules (e.g., aflatoxin B1) with a competitive-type
      assay format. 

PMID- 26291090
TI  - Oral Fluids as a Live-Animal Sample Source for Evaluating Cross-Reactivity and
      Cross-Protection following Intranasal Influenza A Virus Vaccination in Pigs.
AB  - In North American swine, there are numerous antigenically distinct H1 influenza A
      virus (IAV) variants currently circulating, making vaccine development difficult
      due to the inability to formulate a vaccine that provides broad cross-protection.
      Experimentally, live-attenuated influenza virus (LAIV) vaccines demonstrate
      increased cross-protection compared to inactivated vaccines. However, there is no
      standardized assay to predict cross-protection following LAIV vaccination.
      Hemagglutination-inhibiting (HI) antibody in serum is the gold standard correlate
      of protection following IAV vaccination. LAIV vaccination does not induce a
      robust serum HI antibody titer; however, a local mucosal antibody response is
      elicited. Thus, a live-animal sample source that could be used to evaluate LAIV
      immunogenicity and cross-protection is needed. Here, we evaluated the use of oral
      fluids (OF) and nasal wash (NW) collected after IAV inoculation as a live-animal
      sample source in an enzyme-linked immunosorbent assay (ELISA) to predict cross
      protection in comparison to traditional serology. Both live-virus exposure and
      LAIV vaccination provided heterologous protection, though protection was greatest
      against more closely phylogenetically related viruses. IAV-specific IgA was
      detected in NW and OF samples and was cross-reactive to representative IAV from
      each H1 cluster. Endpoint titers of cross-reactive IgA in OF from pigs exposed to
      live virus was associated with heterologous protection. While LAIV vaccination
      provided significant protection, LAIV immunogenicity was reduced compared to live
      virus exposure. These data suggest that OF from pigs inoculated with wild-type
      IAV, with surface genes that match the LAIV seed strain, could be used in an
      ELISA to assess cross-protection and the antigenic relatedness of circulating and
      emerging IAV in swine. 

PMID- 26291093
TI  - Trapping and Characterization of a Single Hydrogen Molecule in a Continuously
      Tunable Nanocavity.
AB  - Using inelastic electron tunneling spectroscopy with the scanning tunneling
      microscope (STM-IETS) and density functional theory calculations (DFT), we
      investigated properties of a single H2 molecule trapped in nanocavities with
      controlled shape and separation between the STM tip and the Au (110) surface. The
      STM tip not only serves for the purpose of characterization, but also is directly
      involved in modification of chemical environment of molecule. The bond length of
      H2 expands in the atop cavity, with a tendency of dissociation when the gap
      closes, whereas it remains unchanged in the trough cavity. The availability of
      two substantially different cavities in the same setup allows understanding of H2
      adsorption on noble metal surfaces and sets a path for manipulating a single
      chemical bond by design. 

PMID- 26291094
TI  - Quantum Calculations of Intramolecular IR Spectra of Ice Models Using Ab Initio
      Potential and Dipole Moment Surfaces.
AB  - We report the IR spectra of two forms of ice in the monomer bend and OH
      stretching regions, using recently developed ab initio potential and dipole
      moment surfaces for arbitrarily many water monomers. Coupling and anharmonicity
      of the intramolecular vibrational modes are taken into account using coupled
      three-mode variational calculations, within the local-monomer model. Spectra for
      the surface and core regions of these ice models are presented. The calculated
      spectra for the core region, with no adjustments, are in good agreement with
      experiment for the intramolecular OH-stretch and bend regions. Our analysis also
      shows a significant contribution from the overtone of the monomer bend to the OH
      stretch region of the spectra. 

PMID- 26291092
TI  - Comparison of Treatment Response in Idiopathic and Connective Tissue Disease
      associated Pulmonary Arterial Hypertension.
AB  - RATIONALE: Studies suggest that patients with connective tissue disease
      associated pulmonary arterial hypertension (CTD-PAH) have a poorer treatment
      response to therapies for PAH compared with patients with idiopathic PAH (IPAH),
      but individual randomized controlled trials (RCTs) have been underpowered to
      examine differences within these subgroups. OBJECTIVES: To compare the effect of
      therapy for PAH in CTD-PAH versus IPAH. METHODS: We obtained individual
      participant data from phase III placebo-controlled RCTs of therapies for PAH
      submitted to the U.S. Food and Drug Administration for drug approval. A treatment
      by-diagnosis interaction term evaluated differences in treatment response between
      CTD-PAH and IPAH. Outcomes included change in 6-minute-walk distance (?6MWD) from
      baseline to 12 weeks, clinical worsening, and all-cause mortality. MEASUREMENTS
      AND MAIN RESULTS: The study sample included 827 participants with CTD-PAH and
      1,935 with IPAH from 11 RCTs. Patients with CTD-PAH had less improvement in 6MWD
      when assigned to active treatment versus placebo compared with patients with IPAH
      (difference in treatment effect on ?6MWD in CTD-PAH vs. IPAH, -17.3 m; 90%
      confidence interval, -31.3 to -3.3; P for interaction = 0.043). Treatment was
      less effective in reducing the occurrence of clinical worsening in CTD-PAH versus
      IPAH (P for interaction = 0.012), but there was no difference in the placebo
      adjusted effect of treatment on mortality (P for interaction = 0.65).
      CONCLUSIONS: Treatment for PAH was less effective in CTD-PAH compared with IPAH
      in terms of increasing 6MWD and preventing clinical worsening. The heterogeneity
      of treatment response supports the need for identifying therapies that are more
      effective for CTD-PAH.

PMID- 26291095
TI  - Two-Dimensional Electronic Spectroscopy Reveals Ultrafast Downhill Energy
      Transfer in Photosystem I Trimers of the Cyanobacterium Thermosynechococcus
      elongatus.
AB  - Two-dimensional electronic spectroscopy (2DES) was used to investigate the
      ultrafast energy-transfer dynamics of trimeric photosystem I of the
      cyanobacterium Thermosynechococcus elongatus. We demonstrate the ability of 2DES
      to resolve dynamics in a large pigment-protein complex containing ~300
      chromophores with both high frequency and time resolution. Monitoring the waiting
      time-dependent changes of the line shape of the inhomogeneously broadened Qy(0-0)
      transition, we directly observe downhill energy equilibration on the 50 fs time
      scale. 

PMID- 26291096
TI  - Surface Polarity and Nanoscale Solvation.
AB  - Linear solvation theories are well established to describe electrostatic
      hydration of small solutes when the hydration free energy is dominated by the
      electrostatic free energy of the solute multipole. In contrast, hydration of
      nanometer solutes is driven by surface hydration. We address the question of
      whether the linear-response thermodynamics established for small multipolar
      solutes applies to surface hydration. To this end, molecular dynamics simulations
      are carried out on a model C180 solute that carries no global multipole, but the
      surface of which is decorated with radially pointing dipoles. Linear response is
      dramatically violated in this case. Further, two crossovers in the solvation
      thermodynamics are discovered as the surface polarity is increased. Both
      transformations produce strongly nonlinear solvation response. The second, more
      collective, crossover leads to a dramatic slowing down of the interfacial
      dynamics, reaching the time-scales of nanoseconds. Our picture offers the
      possibility of flipping water domains at interfaces of nanoparticles and
      biomolecules. 

PMID- 26291097
TI  - [Not Available].

PMID- 26291099
TI  - Thermodynamics of Pore Filling Metal Clusters in Metal Organic Frameworks: Pd in
      UiO-66.
AB  - Metal organic frameworks (MOFs) have experimentally been demonstrated to be
      capable of supporting isolated transition-metal clusters, but the stability of
      these clusters with respect to aggregation is unclear. In this letter we use a
      genetic algorithm together with density functional theory calculations to predict
      the structure of Pd clusters in UiO-66. The cluster sizes examined are far larger
      than those in any previous modeling studies of metal clusters in MOFs and allow
      us to test the hypothesis that the physically separated cavities in UiO-66 could
      stabilize isolated Pd clusters. Our calculations show that Pd clusters in UiO-66
      are, at best, metastable and will aggregate into connected pore filling
      structures at equilibrium. 

PMID- 26291098
TI  - DMSO-Water Clustering in Solution Observed in Soft X-ray Spectra.
AB  - The significant deviation from the ideality of dimethyl sulfoxide (DMSO)/water
      mixtures can be addressed based on the change of the local molecular orbitals of
      each solvent upon mixing. Oxygen K-edge absorption and emission spectra of
      DMSO/water solutions were measured using the liquid microjet technique. The
      spectra demonstrate that the hydrogen bond network in liquid water is already
      influenced at small DMSO concentrations, and at the molar fraction xDMSO = 0.43
      we find strong evidence of DMSO-water clustering reflected by the influence on
      the occupied molecular orbitals. 

PMID- 26291100
TI  - Promoter Effect of Early Stage Grown Surface Oxides: A Near-Ambient-Pressure XPS
      Study of CO Oxidation on PtSn Bimetallics.
AB  - The knowledge of the catalyst active phase on the atomic scale under realistic
      working conditions is the key for designing new and more efficient materials. In
      this context, the investigation of CO oxidation on the bimetallic Pt3Sn(111)
      surfaces by near-ambient-pressure X-ray photoelectron spectroscopy and density
      functional theory calculations illustrates how combining advanced methodologies
      allows the determination of the nature of the active phase. Starting from 300 K
      and 500 mTorr of oxygen, the progressive formation of surface oxides is observed
      with increasing temperature: SnO, PtO units first, and SnO2, PtO2 units
      afterward. For CO oxidation on the (2 * 2) surface, the activity gain is assigned
      to the build-up of ultrathin domains composed of SnO and SnO2 units. The
      formation of these early stage surface oxides is entirely supported by a density
      functional theory analysis. More generally, this study demonstrates how the
      catalyst surface oxidation and transformation can be better controlled by a
      relevant choice of environmental conditions. 

PMID- 26291101
TI  - Photofragmentation Dynamics in Solution Probed by Transient IR Absorption
      Spectroscopy: pisigma*-Mediated Bond Cleavage in p-Methylthiophenol and p
      Methylthioanisole.
AB  - The 267 nm photodissociation dynamics of p-methylthiophenol (p-MePhSH) and p
      methylthioanisole (p-MePhSMe) dissolved in CD3CN have been probed by
      subpicosecond time-resolved broadband infrared spectroscopy. Prompt (tau < 1 ps)
      S-H bond fission in p-MePhSH is confirmed by monitoring the time-evolution of the
      parent (S0) bleach and the transient absorption of the p-MePhS products.
      Vibrational relaxation of the latter occurs on a ~8.5 ps time scale, and ~40% of
      the total radical population undergoes geminate recombination over a ~150 ps time
      scale, yielding (mainly) the p-MePhSH(S0) parent. S-Me bond fission following
      photoexcitation to the S1 state of p-MePhSMe occurs over a much longer timescale,
      with a rate that is very dependent on the degree of vibrational excitation within
      S1. The various findings are compared and contrasted with results from
      complementary gas-phase photofragmentation studies of both molecules, which are
      shown to provide a valuable starting point for describing the solution-phase
      dynamics. 

PMID- 26291102
TI  - Paramagnetic Nanocrystals: Remarkable Lanthanide-Doped Nanoparticles with Varied
      Shape, Size, and Composition.
AB  - Magnetic nanoparticles have been developed in recent years with applications in
      unique and crucial areas such as biomedicine, data storage, environmental
      remediation, catalysis, and so forth. NaYF4 nanoparticles were synthesized and
      isolated with lanthanide dopant percentages, confirmed by ICP-OES measurements,
      of Er, Yb, Tb, Gd, and Dy that were in agreement with the targeted ratios. SEM
      images showed a distinct variation in particle size and shape with dopant type
      and percentage. HRTEM and XRD studies confirmed the particles to be crystalline,
      possessing both alpha and beta phases. Magnetic measurements determined that all
      of the nanoparticles were paramagnetic and did not exhibit a blocking temperature
      from 2 to 300 K. The multifunctional properties of these nanoparticles make them
      suitable for many applications, such as multimodal imaging probes, up-conversion
      fluorescent markers, as well as MRI contrast agents. 

PMID- 26291103
TI  - Natural Atomic Orbital Representation for Optical Spectra Calculations in the
      Exciton Scattering Approach.
AB  - The exciton scattering (ES) method allows efficient calculations of spectroscopic
      observables in large low-dimensional conjugated molecular systems. To compute the
      transition dipoles between the ground and excited electronic states, we should
      extract the ES dipole parameters from quantum chemistry calculations in simple
      molecular fragments. In this manuscript, we show how to retrieve these parameters
      from any reference quantum chemistry model that uses an arbitrary nonorthogonal
      and possibly overcomplete atomic orbital basis set. Our approach relies on the
      natural atomic orbital (NAO) representation, in which the basis functions are
      orthonormal and the atom-like character is preserved. We apply the ES approach,
      combined with the NAO analysis to optical spectra of branched phenylacetylene
      oligomers. Absorption spectra predicted by the ES method demonstrate close
      agreement with the results of direct quantum chemistry calculations, when the
      Time-Dependent Density Functional Theory (TD-DFT) being used as a reference. This
      testifies applicability of a variety of quantum-chemical techniques, where the
      NAO population analysis can be conducted, for the ES framework. 

PMID- 26291104
TI  - Curvature and Frontier Orbital Energies in Density Functional Theory.
AB  - Perdew et al. discovered two different properties of exact Kohn-Sham density
      functional theory (DFT): (i) The exact total energy versus particle number is a
      series of linear segments between integer electron points. (ii) Across an integer
      number of electrons, the exchange-correlation potential "jumps" by a constant,
      known as the derivative discontinuity (DD). Here we show analytically that in
      both the original and the generalized Kohn-Sham formulation of DFT the two
      properties are two sides of the same coin. The absence of a DD dictates deviation
      from piecewise linearity, but the latter, appearing as curvature, can be used to
      correct for the former, thereby restoring the physical meaning of orbital
      energies. A simple correction scheme for any semilocal and hybrid functional,
      even Hartree-Fock theory, is shown to be effective on a set of small molecules,
      suggesting a practical correction for the infamous DFT gap problem. We show that
      optimally tuned range-separated hybrid functionals can inherently minimize both
      DD and curvature, thus requiring no correction, and that this can be used as a
      sound theoretical basis for novel tuning strategies. 

PMID- 26291105
TI  - Fluorescence Excitation Spectra from Individual Chlorosomes of the Green Sulfur
      Bacterium Chlorobaculum tepidum.
AB  - We performed polarization-resolved fluorescence excitation spectroscopy on
      individual chlorosomes from the photosynthetic green sulfur bacterium
      Chlorobaculum tepidum. The experiments were conducted at room temperature and
      under cryogenic conditions. All spectra showed a strong intensity modulation as a
      function of the polarization of the incident radiation, and we determined the
      modulation ratio as a function of the excitation energy. Under ambient conditions
      this ratio shows only little variation across the absorption band, whereas the
      low-temperature experiments clearly revealed that the broad absorption band
      around 740 nm consists of several spectral contributions. 

PMID- 26291106
TI  - Observation of Ultrafast Charge Migration in an Amino Acid.
AB  - We present the first direct measurement of ultrafast charge migration in a
      biomolecular building block - the amino acid phenylalanine. Using an extreme
      ultraviolet pulse of 1.5 fs duration to ionize molecules isolated in the gas
      phase, the location of the resulting hole was probed by a 6 fs visible/near
      infrared pulse. By measuring the yield of a doubly charged ion as a function of
      the delay between the two pulses, the positive hole was observed to migrate to
      one end of the cation within 30 fs. This process is likely to originate from even
      faster coherent charge oscillations in the molecule being dephased by bond
      stretching which eventually localizes the final position of the charge. This
      demonstration offers a clear template for observing and controlling this
      phenomenon in the future. 

PMID- 26291108
TI  - Toward a Universal Water Model: First Principles Simulations from the Dimer to
      the Liquid Phase.
AB  - A full-dimensional model of water, HBB2-pol, derived entirely from "first
      principles", is introduced and employed in computer simulations ranging from the
      dimer to the liquid. HBB2-pol provides excellent agreement with the measured
      second and third virial coefficients and, by construction, reproduces the dimer
      vibration-rotation-tunneling spectrum. The model also predicts the relative
      energy differences between isomers of small water clusters within the accuracy of
      highly correlated electronic structure methods. Importantly, when combined with
      simulation methods that explicitly include zero-point energy and quantum thermal
      motion, HBB2-pol accurately describes both structural and dynamical properties of
      the liquid phase. 

PMID- 26291107
TI  - All-Oxide Photovoltaics.
AB  - Recently, a new field in photovoltaics (PV) has emerged, focusing on solar cells
      that are entirely based on metal oxide semiconductors. The all-oxide PV approach
      is very attractive due to the chemical stability, nontoxicity, and abundance of
      many metal oxides that potentially allow manufacturing under ambient conditions.
      Already today, metal oxides (MOs) are widely used as components in PV cells such
      as transparent conducting front electrodes or electron-transport layers, while
      only very few MOs have been used as light absorbers. In this Perspective, we
      review recent developments of all-oxide PV systems, which until today were mostly
      based on Cu2O as an absorber. Furthermore, ferroelectric BiFeO3-based PV systems
      are discussed, which have recently attracted considerable attention. The
      performance of all-oxide PV cells is discussed in terms of general PV principles,
      and directions for progress are proposed, pointing toward the development of
      novel metal oxide semiconductors using combinatorial methods. 

PMID- 26291110
TI  - Mode Selectivity for a "Central" Barrier Reaction: Eight-Dimensional Quantum
      Studies of the O((3)P) + CH4 -> OH + CH3 Reaction on an Ab Initio Potential
      Energy Surface.
AB  - The dynamics of a combustion reaction, namely, O((3)P) + CH4 -> OH + CH3, is
      investigated with an eight-dimensional quantum model that includes
      representatives of all vibrational modes of CH4 and with a full-dimensional quasi
      classical trajectory (QCT) method. The calculated excitation functions for the
      ground vibrational state CH4 agree well with experiment. Both quantum and QCT
      results suggest that excitation of the stretching modes of CH4 enhances the
      reaction, while the bending and umbrella modes have a smaller impact on
      reactivity, again consistent with experimental findings. However, none of the
      vibrational excitations has comparable efficiency in promoting the reaction as
      translational energy. 

PMID- 26291109
TI  - Proton Tunneling in Heterodimers of Carboxylic Acids: A Rotational Study of the
      Benzoic Acid-Formic Acid Bimolecule.
AB  - Tunneling effects have been measured in the pulsed jet Fourier transform
      microwave spectra of two isotopologues of the benzoic acid-formic acid
      bimolecule. The tunneling splittings are originated by the concerted proton
      transfer of the two carboxylic hydrogens. From the values of these splittings for
      the OH-OH and OD-OD species, it has been possible to model/size the barrier to
      the concerted double proton transfer. 

PMID- 26291111
TI  - Geometric Effect of Single or Double Metal-Tipped CdSe Nanorods on Photocatalytic
      H2 Generation.
AB  - In the present work, we focused on geometrical (single- or double-tipped) and
      compositional (Pt or Au) variations of active metal components in a well-defined
      CdSe nanorod system. These colloidal nanostructures were employed for
      photocatalytic hydrogen generation from water under the identical reaction
      conditions with visible light irradiation. The catalysts exhibited significant
      dependency of the catalytic activity, specifically on the catalyst geometry and
      the choice of the metal tips, determined by the energetic consideration of
      electron transfer to the metal tips and hole transfer to the sacrificial reagents
      on the CdSe nanorods. 

PMID- 26291112
TI  - Photoinduced Interfacial Electron Injection Dynamics in Dye-Sensitized Solar
      Cells under Photovoltaic Operating Conditions.
AB  - We report a pump-probe spectroscopy study of electron injection rates in dye
      sensitized solar cell (DSSC) devices. We examine the case of working devices
      employing an N719 ruthenium sensitizer and an iodide electrolyte. Electron
      injection is found to occur mainly on a sub-100 fs time scale, followed by a
      slower component with a lifetime of 26.9 ps, in accordance with previous reports
      on model samples. The amplitude of this latter component varies with electrolyte
      composition from 25 to 9%. The appearance of slower components in the electron
      injection dynamics may be attributed to an aggregated or weakly bound state of
      the surface-adsorbed N719 sensitizer. Further measurements are reported varying
      the cell light bias and load conditions, revealing no influence on electron
      injection dynamics. No other electron injection event is found to occur up to 1
      ns. These results show no evidence for a slowdown of electron injection under
      working conditions compared to model systems for the electrolytes examined in
      this study. 

PMID- 26291113
TI  - Self-Assembly-Induced Ultrafast Photodriven Charge Separation in Perylene-3,4
      dicarboximide-Based Hydrogen-Bonded Foldamers.
AB  - We report the synthesis, self-assembly characteristics, and ultrafast electron
      transfer dynamics of a perylene-3,4-dicarboximide (PMI) covalently linked to an
      N,N'-bis(3,4,5-tridodecyloxyphenyl)melamine electron donor (D) via a biphenyl
      spacer (PMI-Ph2-D). Synchrotron-based small- and wide-angle X-ray scattering
      (SAXS/WAXS) measurements in methylcyclohexane solution show that PMI-Ph2-D self
      assembles into pi-pi stacked, hydrogen-bonded foldamers consisting of two or
      three hexameric rings or helices. Ultrafast transient absorption spectroscopy
      reveals that photoinduced charge separation within these nanostructures occurs by
      a unique pathway that is emergent in the assembly, whereas electron transfer does
      not occur in the PMI-Ph2-D monomers in tetrahydrofuran. 

PMID- 26291114
TI  - ATR-FTIR Spectroscopy Revealing the Different Vibrational Modes of the
      Selectivity Filter Interacting with K(+) and Na(+) in the Open and Collapsed
      Conformations of the KcsA Potassium Channel.
AB  - The potassium channel is highly selective for K(+) over Na(+), and the
      selectivity filter binds multiple dehydrated K(+) ions upon permeation. Here, we
      applied attenuated total reflection Fourier-transform infrared (ATR-FTIR)
      spectroscopy to extract ion-binding-induced signals of the KcsA potassium channel
      at neutral pH. Shifts in the peak of the amide-I signal towards lower vibrational
      frequencies were observed as K(+) was replaced with Na(+). These ion species
      specific shifts deduced the selectivity filter as the source of the signal, which
      was supported by the spectra of a mutant for the selectivity filter (Y78F). The
      difference FTIR spectra between the solution containing various concentrations of
      K(+) and that containing pure Na(+) demonstrated two types of peak shifts of the
      amide-I vibration in response to the K(+) concentration. These signals represent
      the binding of K(+) ions to the different sites in the selectivity filter with
      different dissociation constants (KD = 9 or 18 mM). 

PMID- 26291115
TI  - Combinatorial Science.

PMID- 26291116
TI  - Subnanometer Thin beta-Indium Sulfide Nanosheets.
AB  - Nanosheets are a peculiar kind of nanomaterials that are grown two-dimensionally
      over a micrometer in length and a few nanometers in thickness. Wide varieties of
      inorganic semiconductor nanosheets are already reported, but controlling the
      crystal growth and tuning their thickness within few atomic layers have not been
      yet explored. We investigate here the parameters that determine the thickness and
      the formation mechanism of subnanometer thin (two atomic layers) cubic indium
      sulfide (In2S3) nanosheets. Using appropriate reaction condition, the growth
      kinetics is monitored by controlling the decomposition rate of the single source
      precursor of In2S3 as a function of nucleation temperature. The variation in the
      thickness of the nanosheets along the polar [111] direction has been correlated
      with the rate of evolved H2S gas, which in turn depends on the rate of the
      precursor decomposition. In addition, it has been observed that the thickness of
      the In2S3 nanosheets is related to the nucleation temperature. 

PMID- 26291117
TI  - Reactivity of Aluminum Clusters with Water and Alcohols: Competition and
      Catalysis?
AB  - An in-depth investigation is presented on the hydrogen evolution reaction of
      aluminum clusters with water and methanol/isopropanol. Aluminum clusters were
      found to undertake an etching effect in the presence of methanol, but also
      resulted in an addition reaction with isopropanol. Such reactivity without
      producing hydrogen is different than water, although they all contain an OH
      group. Further, we studied the competition of water versus alcohols reacting with
      Al clusters by simultaneously introducing them into a fast-flow tube reactor.
      Water dominates the competitive reaction with Al clusters, and the O-H bond in
      water is readily activated to form aluminum hydroxide cluster products. Also
      found is that water functions as a catalyst in the activation of the O-H bond in
      alcohol molecules. 

PMID- 26291118
TI  - Gold-Catalyzed Cycloisomerization and Diels-Alder Reaction of 1,6-Diyne Esters
      with Alkenes and Diazenes to Hydronaphthalenes and -cinnolines.
AB  - A method for the efficient preparation of hydronaphthalene and -cinnoline
      derivatives by Au(I)-catalyzed cycloisomerzation of 1,6-diyne esters followed by
      a Diels-Alder reaction with alkenes or diazenes under mild conditions at room
      temperature with catalyst loadings as low as 1 mol % is described. 

PMID- 26291119
TI  - Syntheses, Crystal Structures, Ion-Exchange, and Photocatalytic Properties of Two
      Amine-Directed Ge-Sb-S Compounds.
AB  - Among numerous heterometallic chalcogenidoantimonates, relatively a few amine
      directed Ge-Sb-S compounds have been synthesized. Presented here are the
      solvothermal syntheses, crystal structures, and ion-exchange, optical, and
      photocatalytic properties of two novel amine-directed Ge-Sb-S compounds, namely,
      [CH3NH3]20Ge10Sb28S72.7H2O (1) and [(CH3CH2CH2)2NH2]3Ge3Sb5S15.0.5(C2H5OH) (2).
      The structure of 1 features an unprecedented two-dimensional Ge-Sb-S double-layer
      composed of two twofold rotational symmetry-related thick [Ge8Sb28S72]n(28n-)
      single layers adhered via vertex-sharing [GeS4] tetrahedra. Compound 2 features a
      unique [Ge3Sb5S15]n(3n-) slab perforated with large elliptic-like windows.
      Remarkably, compound 1 exhibited excellent Cs(+) ion-exchange property despite
      the presence of excess competitive cations, such as Na(+), K(+), Mg(2+), and
      Ca(2+) ions. In addition, compound 1 displayed visible-light-driven
      photocatalytic activity for degradation of rhodamine B. 

PMID- 26291120
TI  - Zooming in: Structural Investigations of Rheologically Characterized Hydrogen
      Bonded Low-Methoxyl Pectin Networks.
AB  - Self-assembled hydrogen-bonded networks of the polysaccharide pectin, a
      mechanically functional component of plant cell walls, have been of recent
      interest as biomimetic exemplars of physical gels, and the microrheological and
      strain-stiffening behaviors have been previously investigated. Despite this
      detailed rheological characterization of preformed gels, little is known about
      the fundamental arrangement of the polymers into cross-linking junction zones,
      the size of these bonded regions, and the resultant network architecture in these
      hydrogen-bonded materials, especially in contrast to the plethora of such
      information available for their well-known calcium-assembled counterparts. In
      this work, in concert with pertinent rheological measurements, an in-depth
      structural study of the hydrogen-bond-mediated gelation of pectins is provided.
      Gels were realized by using glucona-delta-lactone to decrease the pH of solutions
      of pectic polymers that had a (blockwise) low degree of methylesterification.
      Small-angle X-ray scattering and transmission electron microscopy were utilized
      to access structural information on length scales on the order of nanometers to
      hundreds of nanometers, while complementary mechanical properties were measured
      predominantly using small amplitude oscillatory shear rheology. 

PMID- 26291121
TI  - The US Influenza Hospitalization Surveillance Network.
AB  - In 2003, surveillance for influenza in hospitalized persons was added to the
      Centers for Disease Control and Prevention Emerging Infections Program network.
      This surveillance enabled monitoring of the severity of influenza seasons and
      provided a platform for addressing priority questions associated with influenza.
      For enhanced surveillance capacity during the 2009 influenza pandemic, new sites
      were added to this platform. The combined surveillance platform is called the
      Influenza Hospitalization Surveillance Network (FluSurv-NET). FluSurv-NET has
      helped to determine the risk for influenza-associated illness in various segments
      of the US population, define the severity of influenza seasons and the 2009
      pandemic, and guide recommendations for treatment and vaccination programs. 

PMID- 26291122
TI  - Ammonium Iodide Induced Nonradical Regioselective Sulfenylation of Flavones via a
      C-H Functionalization Process.
AB  - A novel and highly regioselective ammonium iodide-induced nonradical
      sulfenylation method for the construction of a C-S bond was developed via C-H
      functionalization. With DMSO or R(1)SO2NHNH2 as a sulfenylating agent, MeS- and
      R(1)S-substituted flavone derivatives were obtained in good yields. This method
      enriches current C-S bond formation chemistry, making it a highly valuable and
      practical method in pharmaceutical industry. 

PMID- 26291123
TI  - pH-Triggered Reversible Multiple Protein-Polymer Conjugation Based on Molecular
      Recognition.
AB  - Polymer conjugation for protein-based therapeutics has been developed
      extensively, but it still suffers from conjugation leading to decrease in protein
      activity and generates complexes with limited diversity due to general classical
      systems only incorporating one protein per each complex. Here we introduce a site
      specific noncovalent protein-polymer conjugation, which can reduce the
      heterogeneity of the conjugates without disrupting protein function, while
      allowing for the modulation of binding affinity and stability, affecting the pH
      dependent binding of the number of proteins per polymer. We compared classical
      one protein-polymer conjugates with multiple protein-polymer conjugates using His
      tagged enhanced yellow fluorescence protein (His6-eYFP) and metal-coordinated
      tris-nitrilotriacetic acid (trisNTA-Me(n+)) in a site-specific way. trisNTA
      Me(n+)-His6 acts as a reversible linker with pH-triggered release of functional
      protein from the trisNTA-functionalized copolymers. The nature of the selected
      Me(n+) and number of available trisNTA-Me(n+) on poly(N-isopropylacrylamide-co
      tris-nitrilotriacetic acid acrylamide) (PNTn) copolymers enables predictable
      modulation of the conjugates binding affinity (0.09-1.35 MUM), stability, cell
      toxicity, and pH responsiveness. This represents a promising platform that allows
      direct control over the properties of multiple protein-polymer conjugates
      compared to the classical single protein-polymer conjugates. 

PMID- 26291125
TI  - Characteristics and associations of pain intensity in patients referred to a
      specialist cancer pain clinic.
AB  - BACKGROUND: Uncontrolled cancer pain (CP) may impair quality of life. Given the
      multidimensional nature of CP, its poor control is often attributed to poor
      assessment and classification. OBJECTIVES: To determine the characteristics and
      associations of pain intensity in a specialist CP clinic. METHODS: Consecutive
      patients referred to the CP clinic of the Portuguese Cancer Institute (Lisbon,
      Portugal) had standardized initial assessments and status documentation of the
      following: Brief Pain Inventory ratings for 'pain now' as the outcome variable;
      initial pain intensity (iPI) on a 0 to 10 scale; pain mechanism (using the
      Douleur Neuropathique 4 tool to assess neuropathic pain); episodic pain; Eastern
      Cooperative Oncology Group rating; oral morphine equivalent daily dose (MEDD);
      Hospital Anxiety Depression Scale and Emotional Thermometer scores; and cancer
      diagnosis, metastases, treatment and pain duration. Univariable analyses were
      conducted to test the association of independent variables with iPI. Variables
      with P<0.1 were entered into a multivariable regression model, using backward
      elimination and a cut-point of P=0.2 for final model selection. RESULTS: Of 371
      participants, 285 (77%) had moderate (4 to 6) or severe (7 to 10) iPI. The
      initial median MEDD was relatively low (30 mg [range 20 mg to 60 mg]). In the
      multivariable model, higher income, Eastern Cooperative Oncology Group rating 3
      to 4, cancer diagnosis (head and neck, genitourinary and gastrointestinal),
      adjuvant use and initial MEDD were associated with iPI (P<0.05). The model's R2
      was 18.6, which explained only 19% of iPI variance. CONCLUSIONS: The diversity of
      factors associated with pain intensity and their limited explanation of its
      variance underscore the biopsychosocial complexity of CP. Adequacy of CP
      management warrants further exploration.

PMID- 26291124
TI  - Supporting chronic pain management across provincial and territorial health
      systems in Canada: Findings from two stakeholder dialogues.
AB  - BACKGROUND: Chronic pain is a serious health problem given its prevalence,
      associated disability, impact on quality of life and the costs associated with
      the extensive use of health care services by individuals living with it.
      OBJECTIVE: To summarize the research evidence and elicit health system
      policymakers', stakeholders' and researchers' tacit knowledge and views about
      improving chronic pain management in Canada and engaging provincial and
      territorial health system decision makers in supporting comprehensive chronic
      pain management in Canada. METHODS: For these two topics, the global and local
      research evidence regarding each of the two problems were synthesized in evidence
      briefs. Three options were generated for addressing each problem, and
      implementation considerations were assessed. A stakeholder dialogue regarding
      each topic was convened (with 29 participants in total) and the deliberations
      were synthesized. RESULTS: To inform the first stakeholder dialogue, the authors
      found that systematic reviews supported the use of evidence-based tools for
      strengthening chronic pain management, including patient education, self
      management supports, interventions to implement guidelines and multidisciplinary
      approaches to pain management. While research evidence about patient
      registries/treatment-monitoring systems is limited, many dialogue participants
      argued that a registrysystem is needed. Many saw a registry as a precondition for
      moving forward with other options, including creating a national network of
      chronic pain centres with a coordinating 'hub' to provide chronic pain-related
      decision support and a cross-payer, cross-discipline model of patient-centred
      primary health care-based chronic pain management. For the second dialogue,
      systematic reviews indicated that traditional media can be used to positively
      influence individual health-related behaviours, and that multistakeholder
      partnerships can contribute to increasing attention devoted to issues on policy
      agendas. Dialogue participants emphasized the need to mobilize behind an effort
      to build a national network that would bring together existing organizations and
      committed individuals. CONCLUSIONS: Developing a national network and,
      thereafter, a national pain strategy are important initiatives that garnered
      broad-based support during the dialogues. Efforts toward achieving this goal have
      been made since convening the dialogues.

PMID- 26291126
TI  - Use of calcitonin in recalcitrant phantom limb pain complicated by heterotopic
      ossification.
AB  - BACKGROUND: Phantom limb pain (PLP) is a common complication after amputation,
      affecting up to 80% of the amputee population. However, only 5% to 10% of
      amputees have severe PLP impacting daily function. The present report details the
      management of severe, treatment-resistant PLP in a 72-year-old man with a
      traumatic left transradial amputation and a comorbid complication of heterotopic
      ossification (HO). OBJECTIVE: To describe a case of PLP with HO and the possible
      role of calcitonin in the treatment of both conditions. METHODS: A systematic
      review of the literature regarding the management of PLP. RESULTS: Seventeen
      articles that directly addressed PLP were identified; 11 were randomized
      controlled trials. All involved small samples and follow-up ranged from 6 h to
      one year, with the majority limited to six weeks. DISCUSSION: In the present
      case, medication management was limited by side effects, lack of response and the
      patient's desire to avoid long-term medication. Investigations revealed HO, which
      was suspected to envelop the median nerve in the proximal forearm. After several
      unsuccessful medication trials, the literature was reviewed in search of common
      variables between HO formation and persistent PLP. Ultimately, the biochemical
      effects associated with nerve injury were identified to be a possible factor in
      both HO and PLP development. Calcitonin's proposed mechanisms of action may help
      to manage HO and PLP at multiple stages of disease development and maintenance.
      In the present case, a four-week trial of intranasal calcitonin was successful,
      with pain control lasting at least 18 months. CONCLUSION: The present case report
      provided a review of the current literature in PLP pharmacological management and
      the current understanding of the etiology of PLP and HO, as well as how the two
      may coexist. It also provided an opportunity to discuss the proposed mechanisms
      of action of calcitonin in the management of PLP and HO.

PMID- 26291127
TI  - Use of electronic health records for early detection of high-cost, low back pain
      patients.
AB  - BACKGROUND: Low back pain (LBP) is a debilitating condition that is complex to
      manage. One reason is that clinicians lack means to identify early on patients
      who are likely to become high care utilizers. OBJECTIVE: To explore the
      feasibility of developing a 'dynamic' predictive model using electronic health
      record data to identify costly LBP patients within the first year after their
      initial LBP encounter with a primary care provider. Dynamic, in this context,
      indicates a process in which the decision on how to manage patients is dependent
      on whether they are at their first, second or third LBP visit with the provider.
      METHODS: A series of logistic regression models was developed to predict who will
      be a high-cost patient (defined as top 30% of the cost distribution) at each of
      the first three LBP visits. RESULTS: The c-statistics of the three logistic
      regression models corresponding to each of the first three visits were 0.683,
      0.795 and 0.741, respectively. The overall sensitivity of the model was 42%, the
      specificity was 86% and the positive predictive value was 48%. Men were more
      likely to become expensive than women, while patients who had workers'
      compensation as their primary payer type had higher use of prescription opioid
      drugs or were smokers before the first LBP visit were also more likely to become
      expensive. CONCLUSION: The results suggest that it is feasible to develop a
      dynamic, primary care provider visit-based predictive model for LBP care based on
      longitudinal data obtained via electronic health records.

PMID- 26291129
TI  - MAPK15 mediates BCR-ABL1-induced autophagy and regulates oncogene-dependent cell
      proliferation and tumor formation.
AB  - A reciprocal translocation of the ABL1 gene to the BCR gene results in the
      expression of the oncogenic BCR-ABL1 fusion protein, which characterizes human
      chronic myeloid leukemia (CML), a myeloproliferative disorder considered
      invariably fatal until the introduction of the imatinib family of tyrosine kinase
      inhibitors (TKI). Nonetheless, insensitivity of CML stem cells to TKI treatment
      and intrinsic or acquired resistance are still frequent causes for disease
      persistence and blastic phase progression experienced in patients after initial
      successful therapies. Here, we investigated a possible role for the MAPK15/ERK8
      kinase in BCR-ABL1-dependent autophagy, a key process for oncogene-induced
      leukemogenesis. In this context, we showed the ability of MAPK15 to physically
      recruit the oncogene to autophagic vesicles, confirming our hypothesis of a
      biologically relevant role for this MAP kinase in signal transduction by this
      oncogene. Indeed, by modeling BCR-ABL1 signaling in HeLa cells and taking
      advantage of a physiologically relevant model for human CML, i.e. K562 cells, we
      demonstrated that BCR-ABL1-induced autophagy is mediated by MAPK15 through its
      ability to interact with LC3-family proteins, in a LIR-dependent manner.
      Interestingly, we were also able to interfere with BCR-ABL1-induced autophagy by
      a pharmacological approach aimed at inhibiting MAPK15, opening the possibility of
      acting on this kinase to affect autophagy and diseases depending on this cellular
      function. Indeed, to support the feasibility of this approach, we demonstrated
      that depletion of endogenous MAPK15 expression inhibited BCR-ABL1-dependent cell
      proliferation, in vitro, and tumor formation, in vivo, therefore providing a
      novel "druggable" link between BCR-ABL1 and human CML. 

PMID- 26291128
TI  - Telomere biology: Rationale for diagnostics and therapeutics in cancer.
AB  - The key step of carcinogenesis is the malignant transformation which is
      fundamentally a telomere biology dysfunction permitting cells to bypass the
      Hayflick limit and to divide indefinitely and uncontrollably. Thus all partners
      and structures involved in normal and abnormal telomere maintenance, protection
      and lengthening can be considered as potential anti-cancer therapeutic targets.
      In this Point of View we discuss, highlight and provide new perspectives from the
      current knowledge and understanding to position the different aspects of telomere
      biology and dysfunction as diagnostic, preventive and curative tools in the field
      of cancer. 

PMID- 26291130
TI  - Salarin C inhibits the maintenance of chronic myeloid leukemia progenitor cells.
AB  - We previously showed that incubation of chronic myeloid leukemia (CML) cells in
      very low oxygen selects a cell subset where the oncogenetic BCR/Abl protein is
      suppressed and which is thereby refractory to tyrosine kinase inhibitors used for
      CML therapy. In this study, salarin C, an anticancer macrolide extracted from the
      Fascaplysinopsis sponge, was tested as for its activity on CML cells, especially
      after their incubation in atmosphere at 0.1% oxygen. Salarin C induced mitotic
      cycle arrest, apoptosis and DNA damage. Salarin C also concentration-dependently
      inhibited the maintenance of stem cell potential in cultures in low oxygen of
      either CML cell lines or primary cells. Surprisingly, the drug also concentration
      dependently enforced the maintenance of BCR/Abl signaling in low oxygen, an
      effect which was paralleled by the rescue of sensitivity of stem cell potential
      to IM. These results suggest a potential use of salarin C for the suppression of
      CML cells refractory to tyrosine kinase inhibitors.

PMID- 26291132
TI  - To the Editor: Concerning Rodriguez et al.

PMID- 26291131
TI  - Effects of sex and gender in ten types of psychotherapy.
AB  - OBJECTIVE: This paper addresses the results of two samples of a large
      naturalistic (effectiveness study) outpatient process-outcome study in
      Switzerland (Practice-Oriented Outpatient Psychotherapy Study). Ten different
      types of psychotherapy were investigated by looking at the role of the sex or
      gender of therapists and patients with regard to treatment outcome by including
      several nonspecific therapeutic factors. METHOD: Ten different types of
      psychotherapy, 237 patients, and 68 therapists were included in the study. A
      subsample of 116 cases was analyzed with regard to therapists' technical
      interventions. RESULTS: Sex and gender issues of both therapists and patients did
      not play a crucial role in any type of psychotherapy investigated. Gender issues
      appeared to play an indirect role. Female therapists intervene more empathically,
      whereas male therapists tend to use more confrontational techniques. CONCLUSIONS:
      Since the results show that therapists differ substantially with regard to their
      intervention techniques due to their sex, they should become more conscious of
      their interventions by considering patients' severity of psychological problems
      and patients' level of psychological functioning so as to not over or
      underchallenge them.

PMID- 26291133
TI  - HIV testing practices among Latina women at risk of getting infected: a five-year
      follow-up of a community sample in South Florida.
AB  - Latinos are more likely to delay HIV testing, present to care with an AIDS
      defining illness, and die within one year of learning their HIV-positive status
      than non-Latino blacks and whites. For this paper, we explore the role of partner
      relationship characteristics and health behaviors, in predicting HIV testing
      among Latina adult women who engaged in risky sexual behaviors (i.e., unprotected
      vaginal and/or anal sex). Data from a convenience sample of 168 Latina adult
      women who engaged in risky sexual behavior in the year prior to assessment were
      analyzed for this paper. Rates and predictors of HIV testing among this sample
      were assessed after a five-year follow-up. Descriptive and analytical estimates
      include incidence rates and adjusted odds ratios (AOR) from multilevel models. At
      five-year follow-up, 63.7% (n = 107) women reported having been tested for HIV,
      of whom 12.2% (n = 13) were women who never tested before. Main reasons for not
      having been tested at follow-up included: low risk perception (62.1%) and
      trusting their partner(s)/being in a monogamous relationship/knowing their
      partner's HIV status (17.2%). Predictors of HIV testing included: age (AOR: 0.96;
      95% CI = 0.92-0.99), provider endorsement of HIV testing (AOR: 4.59; 95% CI =
      1.77-11.95), poor quality of their romantic relationships (AOR: 1.12; 95% CI =
      1.03-1.26), and knowing the HIV sero-status of sexual partner (AOR: 3.61; 95% CI
      = 1.46-8.95). This study characterizes a group of Latina women at high risk for
      HIV infection and their HIV testing behaviors. Our findings underscore the need
      of increasing access to quality health-care services and HIV behavioral
      interventions, and to strengthen the adherence to HIV/sexually transmitted
      disease testing recommendations and guidelines among local health-care providers
      serving the Latino community in South Florida.

PMID- 26291134
TI  - Age at asthma onset and asthma self-management education among adults in the
      United States.
AB  - OBJECTIVE: Asthma self-management education improves asthma-related outcomes. We
      conducted this analysis to evaluate variation in the percentages of adults with
      active asthma reporting components of asthma self-management education by age at
      asthma onset. METHODS: Data from 2011 to 2012 Asthma Call-back Surveys were used
      to estimate percentages of adults with active asthma reporting six components of
      asthma self-management education. Components of asthma self-management education
      include having been taught to what to do during an asthma attack and receiving an
      asthma action plan. Differences in the percentages of adults reporting each
      component and the average number of components reported across categories of age
      at asthma onset were estimated using linear regression, adjusted for age,
      education, race/ethnicity, sex, smoking status, and years since asthma onset.
      RESULTS: Overall, an estimated 76.4% of adults with active asthma were taught
      what to do during an asthma attack and 28.7% reported receiving an asthma action
      plan. Percentages reporting each asthma self-management education component
      declined with increasing age at asthma onset. Compared with the referent group of
      adults whose asthma onset occurred at 5-14 years of age, the percentage of adults
      reporting being taught what to do during an asthma attack was 10% lower among
      those whose asthma onset occurred at 65-93 years of age (95% CI: -18.0, -2.5) and
      the average number of components reported decreased monotonically across
      categories of age at asthma onset of 35 years and older. CONCLUSIONS: Among
      adults with active asthma, reports of asthma self-management education decline
      with increasing age at asthma onset.

PMID- 26291135
TI  - Decisional conflict in asthma patients: a cross sectional study.
AB  - OBJECTIVE: This study aimed at determining the level of decisional conflict in
      asthmatic individuals facing recommendation-based decisions provided to improve
      asthma control. METHODS: This was a cross-sectional study performed on a
      convenience sample of 50 adults aged between 18 and 65 years with a diagnosis of
      asthma. They completed a decisional conflict scale (possible range of 0-100%),
      asthma knowledge and control questionnaires (both 0% and 100%), and a general
      questionnaire on socio-demographic characteristics. A decisional conflict was
      considered clinically significant with a score greater than 37.5%. Simple
      descriptive statistics were used to investigate associations with decisional
      conflict. RESULTS: Participants were mainly women (76%) and diagnosed with mild
      asthma (72%). The median age (1st and 3rd quartile) was 25 years (22 and 42). The
      median score (1st and 3rd quartile) of decisional conflict was 33% (24 and 44). A
      clinically significant score (>37.5%) was obtained in 36% of subjects. A
      statistically significant negative correlation between the knowledge score and
      the decisional conflict score (r(p) = -0.38; p = 0.006) was observed. The level
      of knowledge was the only statistically independent variable associated with the
      decisional conflict score (p = 0.0043). CONCLUSIONS: A considerable proportion of
      patients with asthma have a clinically significant level of decisional conflict
      when facing decisions aimed at improving asthma control. Patients with poor
      knowledge of asthma are more at risk of clinically significant level of
      decisional conflict. These findings support the relevance of providing asthmatic
      patients with relevant information in decision aids.

PMID- 26291136
TI  - A case of uncontrolled severe asthma patient with coexisting carcinoid tumor
      presenting as pneumomediastinum.
AB  - INTRODUCTION: Patients with inadequately controlled or uncontrolled asthma are at
      a greater risk of attacks for asthma requiring emergency room visits or hospital
      admissions. There is a significant correlation between the severity of the
      disease and the severity of exacerbations. Patients with poorly controlled asthma
      are at a higher risk for complications. CASE STUDY: We present a 24-year-old
      aspirin-intolerant, uncontrolled asthma patient with the complication of
      pneumomediastinum. RESULTS: Severe symptoms persisted after the resolution of the
      pneumomediastinum despite intense anti-inflammatory and anti-obstructive therapy.
      A bronchoscopy revealed an endobronchial lesion and she was diagnosed with a
      carcinoid tumor. CONCLUSION: This case is an example of the importance of re
      evaluating asthma patients who do not respond to standard medical treatment.
      Clinicians should be aware of the complications associated with asthma attacks
      such as pneumomediastinum and the possibility of a differential diagnosis that
      worsen asthma symptoms such as a carcinoid tumor.

PMID- 26291138
TI  - Prevalence of over-/misdiagnosis of asthma in patients referred to an allergy
      clinic.
AB  - OBJECTIVE: Increasing asthma incidence may be due to an overall increase in
      asthma awareness by physicians, potentially resulting in overdiagnosis. One of
      the unique features of asthma is bronchial hyperresponsiveness, which can be
      assessed by methacholine bronchial challenge (MBC). Overdiagnosis may result in
      over- or mistreatment. The aims of this study were to describe the prevalence of
      the over-/misdiagnosis of asthma and the use of anti-asthmatic drugs in patients
      with asthma-like symptoms who had not yet undergone a respiratory function
      assessment to confirm the diagnosis of asthma. METHODS: This was a retrospective
      study analyzing all MBCs performed by our Outpatient Allergy Clinic in a two-year
      period to confirm/exclude the diagnosis of asthma in patients referred by general
      practitioners and complaining of asthma-like symptoms. Anti-asthmatic medications
      used by the patients until the MBC date were recorded. RESULTS: 43.8% of the
      reviewed MBCs were positive and 37.4% of the patients with a positive MBC were
      previously taking anti-asthmatic drugs (568.8 +/- 76.4 mcg mean beclomethasone
      equivalents), compared to 51.2% of those patients with a negative MBC (464.8 +/-
      57.8 mcg). No differences were found in the daily doses of inhaled
      corticosteroids or other anti-asthmatic drugs, or in the duration of treatment
      before the assessment of bronchial hyperresponsiveness. CONCLUSIONS: A sizeable
      percentage of subjects who reported physician-diagnosed asthma had a negative
      MBC. Nevertheless, a greater proportion of negative MBC patients were taking anti
      asthmatic drugs compared to those with a confirmed diagnosis of asthma,
      illustrating that the overdiagnosis of asthma may lead to over- and mistreatment
      of respiratory symptoms.

PMID- 26291139
TI  - Postural stability in school-age children with mild bronchial asthma disease (a
      pilot study).
AB  - OBJECTIVE: This study assessed the postural stability in children with asthma
      using balance tests under conditions of a comfortable foot placement and with a
      foot placement provoking instability. METHODS: A group of 10 school children from
      8 to 10 years old with mild intermittent asthma and 10 healthy children of the
      same age range performed four balance tests in a randomized order: preferred
      stance, adjusted stance, and tandem stance each under both conditions of eyes
      opened (EO) and eyes closed (EC), as well as a one-legged stance with eyes-opened
      conditions. To determine postural stability, the center of pressure (CoP)
      movement was recorded. Basic stabilographic parameters were calculated: CoP
      velocity in the anterior-posterior direction, CoP velocity in the medial-lateral
      direction, and the total CoP velocity. RESULTS: Statistically significant
      differences between the groups were found only for the one-legged stance.
      Significantly greater anterior-posterior CoP velocity (p = 0.05) and total CoP
      velocity (p = 0.03) were found in children with asthma when standing on the
      preferred foot. A significantly greater medial-lateral velocity (p = 0.02) was
      also found in the non-preferred foot of children with asthma. CONCLUSIONS: We can
      conclude that standing on one leg might be an appropriate test with which to
      identify balance differences between young children with mild intermittent asthma
      and healthy children.

PMID- 26291137
TI  - Fluticasone furoate (FF)/vilanterol (100/25 mcg or 200/25 mcg) or FF (100 mcg) in
      persistent asthma.
AB  - OBJECTIVES: Fluticasone furoate (FF; inhaled corticosteroid) combined with
      vilanterol (VI; long-acting beta(2) agonist) is a once-daily therapy for asthma
      and chronic obstructive pulmonary disease. This 12-week phase III study compared
      the efficacy and safety of once-daily (evening dosing) FF/VI 100/25 mcg versus FF
      100 mcg (primary objective) and FF/VI 100/25 mcg versus FF/VI 200/25 mcg
      (descriptive comparison only) in patients (n = 1039) >=12 years with moderate-to
      severe persistent asthma. METHODS: The primary end point was weighted mean (wm) 0
      24-h serial forced expiratory volume in 1 s (FEV(1)) at week 12. Secondary end
      points (change from baseline) were trough FEV(1) and the proportion (%) of rescue
      free 24-h periods (both powered), the proportion (%) of symptom-free 24-h
      periods, and morning and evening peak expiratory flow (PEF). Safety data (adverse
      events, AEs) were collected throughout. RESULTS: Compared with FF 100 mcg, FF/VI
      100/25 mcg significantly improved wmFEV(1) (p < 0.001), trough FEV(1) (p =
      0.014), % rescue-free (p < 0.001), % symptom-free (p = 0.002) 24-h periods, and
      morning and evening PEF (p < 0.001). FF/VI 200/25 mcg produced small numerical
      improvements versus FF/VI 100/25 mcg for all end points. Incidence of AEs was
      similar across groups. CONCLUSIONS: FF/VI 100/25 mcg resulted in significant
      improvements in all primary and secondary end points versus FF 100 mcg. Numerical
      improvements occurred with FF/VI 200/25 mcg versus FF/VI 100/25 mcg. All
      treatments were well tolerated.

PMID- 26291140
TI  - The role of impulse oscillometry in detecting airway dysfunction in athletes.
AB  - BACKGROUND: Impulse oscillometry (IOS) has previously been proposed to provide
      greater sensitivity than spirometry when employed with indirect
      bronchoprovocation testing for the diagnosis of airway dysfunction in athletes.
      However, this recommendation is based on a highly selected population of
      symptomatic patients. OBJECTIVE: To compare IOS, spirometry and respiratory
      symptoms following indirect bronchoprovocation in a screened cohort of athletes.
      METHODS: One hundred and one recreational athletes were recruited. Respiratory
      symptoms were assessed via the Dyspnoea-12 questionnaire. Spirometry and IOS were
      performed pre and post a eucapnic voluntary hyperpnoea (EVH) challenge. RESULTS:
      Ninety-four athletes completed the study. Sixteen athletes (17%) were positive
      for airway dysfunction based on spirometry (i.e. >= 10% fall in FEV1) and 17
      athletes (18%) based on IOS (i.e. >= 50% increase in R5). Only nine athletes
      (10%) met both diagnostic thresholds. A poor relationship was observed between
      respiratory symptoms (i.e. Dyspnoea-12 score) and all spirometry and IOS
      variables. A direct relationship was observed between percentage change in R5 (r
      = 0.65), Z5 (r = 0.68), RF (r = 0.65), AX (r = 0.69) and the maximum fall in FEV1
      (DeltaFEV1max; p < 0.001). A weak relationship was observed between R20 (r =
      0.27), X5 (r = 0.37) and DeltaFEV1max (p < 0.01). CONCLUSION: Impulse
      oscillometry and spirometry do not concur precisely following indirect
      bronchoprovocation. However, IOS detects additional cases of airway dysfunction
      in athletes and therefore may provide diagnostic value in this population.
      Further work is required to establish diagnostic thresholds and fully determine
      the place of IOS in screening athletes for airway dysfunction.

PMID- 26291141
TI  - A snapshot of pharmacist attitudes and behaviors surrounding the management of
      pediatric asthma.
AB  - OBJECTIVE: The aim of this study is to identify the current status of pediatric
      asthma management in the Australian community pharmacy setting from the
      pharmacists' perspective. This research will allow us to identify training needs
      of community pharmacists. METHOD: Pharmacists were recruited from the Sydney
      metropolitan region and asked to complete a self-reported questionnaire that
      elucidated information on four general domains relating to pediatric asthma
      management within community pharmacy. All data collected were analysed
      descriptively. Bivariate Pearson correlations were performed to determine whether
      interrelationships existed between specific domains. RESULTS: All 77 pharmacists
      completed the questionnaire. Thirty-two percent had not completed any asthma
      related CPD in the past year and only 25% of pharmacists reported using the
      national asthma guidelines in practice. Just over half of the pharmacists (54%)
      reported that they provide device technique demonstrations for new inhaled
      medicines, and 35% of pharmacists reported that they check for written asthma
      self-management plan possession. Although 65% of pharmacists reported confidence
      in communication skills, most pharmacists were not confident in setting short
      /long-term goals with the patient and carer for managing asthma at home.
      Pharmacists believed that they are just as effective as doctors in providing
      asthma counseling and education. Lack of time was identified as a significant
      barrier. CONCLUSION: We have identified a gap between guideline recommended
      practices and the self-reported practices of community pharmacists. Pharmacists
      need more appropriate continuing education programs that can translate into
      improved pediatric asthma self-management practices and thus improved asthma
      outcomes in children. This may require an alternative approach.

PMID- 26291142
TI  - Occurrences of Oestrus ovis parasitism in necropsied sheep in the Umuarama
      microregion, Parana, Brazil.
AB  - Between January 2007 and September 2013, 71 sheep belonging to 12 farms in the
      Umuarama microregion, State of Parana, were evaluated regarding presence of
      Oestrus ovis larvae, during necropsies. The farms from which these animals
      originated were visited and the owners and employees were interviewed.
      Occurrences of O. ovis parasitism in sheep were diagnosed for the first time on
      this microregion. Of the 71 animals, 12 (16.9%) were parasitized by O. ovis, with
      mean intensity of 2.25 larvae per infested head (1 to 8 larvae/infested head).
      There was a high correlation (0.81, p=0.0346) between the number of larvae and
      the macroscopic lesions observed in these animals' nasal cavities, such that
      sheep with more than 3 larvae may contain mucupurulent secretions or epistaxis.
      From the interviews conducted, it was found that all the farm owners were
      applying chemical parasite control methods (helminths and/or O. ovis),
      administered to all animals in the herds every 30 days (91.6% of the producers),
      using derivatives of macrocyclic lactones and/or benzimidazoles/imidazothiazoles.
      Further studies need to be conducted in this particular region, in an attempt to
      elucidate the prevalence of O. ovis parasitism in herds. 

PMID- 26291143
TI  - Prevalence and risk factors for Toxoplasma gondii in sheep in the State of
      Paraiba, Northeastern Brazil.
AB  - The aims of this survey were to determine the flock-level and animal-level
      prevalences of anti-Toxoplasma gondii antibodies in sheep in the State of
      Paraiba, Northeastern Brazil, and to identify risk factors. Blood samples were
      collected from 540 sheep in 63 flocks in 14 municipalities in the Sertao
      mesoregion. To serologically diagnose T. gondiii nfection, the indirect
      immunofluorescent antibody test (IFAT) was used. Flocks with at least one
      seropositive animal were considered positive. Among the 63 flocks, 28 (44.44%)
      were positive, and 60 (11.11%) of the 540 animals were seropositive. Variable
      flock size > 25 animals was identified as a risk factor (odds ratio = 3.2; 95% CI
      = 1.09 - 9.34; P = 0.033). The results from this survey demonstrate that T.
      gondii is spread among sheep in the State of Paraiba.

PMID- 26291144
TI  - Amblyomma nodosum (Neumann, 1899): observations on life cycle under laboratory
      conditions.
AB  - The natural hosts of Amblyomma nodosum in the immature stages are a variety of
      birds and the anteater in the adult stage. However, so far no data have been
      published about this tick's life cycle. To fill this gap, a record was made of
      its development under laboratory conditions. All the procedures were controlled
      in a BOD chamber set at 27+/-1  degrees C and 80+/-10% relative humidity and
      scotophase. The parasitic stages were raised on rabbits (Oryctolagus cuniculus
      Linnaeus, 1758), from which more than 50% of larvae and nymphs were recovered,
      although only a small portion performed ecdysis. The adults did not fixed on the
      rabbits, which suggests that the experimental conditions were unsuitable for the
      requirements of this species. The data obtained here indicate that A. nodosum is
      highly dependent on its host and environment whereas under laboratory conditions
      and host chosen for the study was not obtained satisfactory results and new
      studies with different hosts and new environmental conditions should be
      elaborated. 

PMID- 26291145
TI  - Recombinant gp19 as a potential antigen for detecting anti-Ehrlichia canis
      antibodies in dog sera.
AB  - The canine monocytic ehrlichiosis, caused by Ehrlichia canis, is endemic in
      several regions of Brazil. Some serological diagnostic techniques using
      immunodominant proteins of E. canis as antigens are available, but their
      specificities and sensitivities are questionable. Based on this, the objective of
      this study was to test the antigenic potential of the recombinant gp19 protein
      (rGP19) for subsequent use in diagnostic tests. The rGP19 expressed in the
      Escherichia coli strain BL21 (DE3) C41 was recognized in the sera from
      experimentally infected dogs using ELISA and Western blotting. Thus, it was
      possible to obtain a promising antigen with the ability to differentiate between
      E. canis-positive and -negative animals, even 1 week after infection. 

PMID- 26291146
TI  - Ascaris suum in pigs of the Zona da Mata, Minas Gerais State, Brazil.
AB  - Among the parasites that affect pigs, Ascaris suum stands out for causing the
      greatest losses to livestock production systems. This parasite can be monitored
      during the slaughter of animals through the identification of "milk spots" or
      white patches on the liver caused by its larval migration. However, infection in
      the herd is usually subclinical, which is why the presence of this parasite in
      industrial pig production has been overlooked. The aim of the study was therefore
      to evaluate the occurrence of milk spots on the liver of animals slaughtered in
      the micro-region of Ponte Nova in the Zona da Mata - Minas Gerais, Brazil, and to
      associate these lesions with the time of year, herd size and source of origin of
      the animals. An evaluation was made of 1,069 lots, totaling 108,073 animals,
      based on data extracted from the Federal Inspection Service. The animals were
      slaughtered during the period of January 2011 to June 2013. Out of the total
      number of slaughtered animals, 10,535 (9.75%) tested positive for these lesions.
      Therefore, veterinarians and producers should be warned about the inefficiency of
      the deworming protocols that are used, and the need to develop and/or review
      control strategies for this parasite in production systems. 

PMID- 26291147
TI  - Occurrence of Cryptosporidium spp. and Giardia spp. in a public water-treatment
      system, Parana, Southern Brazil.
AB  - The purpose of this study was to investigate the occurrence of Cryptosporidium
      spp. and Giardia spp. in a public water-treatment system. Samples of raw and
      treated water were collected and concentrated using the membrane filtration
      technique. Direct Immunofluorescence Test was performed on the samples. DNA
      extraction using a commercial kit was performed and the DNA extracted was
      submitted to a nested-PCR reaction (n-PCR) and sequencing. In the
      immunofluorescence, 2/24 (8.33%) samples of raw water were positive for Giardia
      spp.. In n-PCR and sequencing, 2/24 (8.33%) samples of raw water were positive
      for Giardia spp., and 2/24 (8.33%) samples were positive for Cryptosporidium
      spp.. The sequencing showed Cryptosporidium parvum and Giardia duodenalis DNA. In
      raw water, there was moderate correlation among turbidity, color and
      Cryptosporidium spp. and between turbidity and Giardia spp.. The presence of
      these protozoans in the water indicates the need for monitoring for water
      treatment companies. 

PMID- 26291148
TI  - Breast cancer diagnosis using spatial light interference microscopy.
AB  - The standard practice in histopathology of breast cancers is to examine a
      hematoxylin and eosin (H&E) stained tissue biopsy under a microscope to diagnose
      whether a lesion is benign or malignant. This determination is made based on a
      manual, qualitative inspection, making it subject to investigator bias and
      resulting in low throughput. Hence, a quantitative, label-free, and high
      throughput diagnosis method is highly desirable. We present here preliminary
      results showing the potential of quantitative phase imaging for breast cancer
      screening and help with differential diagnosis. We generated phase maps of
      unstained breast tissue biopsies using spatial light interference microscopy
      (SLIM). As a first step toward quantitative diagnosis based on SLIM, we carried
      out a qualitative evaluation of our label-free images. These images were shown to
      two pathologists who classified each case as either benign or malignant. This
      diagnosis was then compared against the diagnosis of the two pathologists on
      corresponding H&E stained tissue images and the number of agreements were
      counted. The agreement between SLIM and H&E based diagnosis was 88% for the first
      pathologist and 87% for the second. Our results demonstrate the potential and
      promise of SLIM for quantitative, label-free, and high-throughput diagnosis.

PMID- 26291149
TI  - Parametric study of orthopedic insole of valgus foot on partial foot amputation.
AB  - Orthopedic insole was important for partial foot amputation (PFA) to achieve foot
      balance and avoid foot deformity. The inapposite insole orthosis was thought to
      be one of the risk factors of reamputation for foot valgus patient, but
      biomechanical effects of internal tissues on valgus foot had not been clearly
      addressed. In this study, plantar pressure on heel and metatarsal regions of PFA
      was measured using F-Scan. The three-dimensional finite element (FE) model of
      partial foot evaluated different medial wedge angles (MWAs) (0.0 degrees -10.0
      degrees ) of orthopedic insole on valgus foot. The effect of orthopedic insole on
      the internal bone stress, the medial ligament tension of ankle, plantar fascia
      tension, and plantar pressure was investigated. Plantar pressure on medial heel
      region was about 2.5 times higher than that of lateral region based on the F-Scan
      measurements. FE-predicted results showed that the tension of medial ankle
      ligaments was the lowest, and the plantar pressure was redistributed around the
      heel, the first metatarsal, and the lateral longitudinal arch regions when MWA of
      orthopedic insole ranged from 7.5 degrees  to 8.0 degrees . The plantar fascias
      maintained about 3.5% of the total load bearing on foot. However, the internal
      stresses from foot bones increased. The simulation in this study would provide
      the suggestion of guiding optimal design of orthopedic insole and therapeutic
      planning to pedorthist.

PMID- 26291150
TI  - Prediction of Hearing Loss Due to Cisplatin Chemoradiotherapy.
AB  - IMPORTANCE: Patients with head and neck cancer may experience chemoradiotherapy
      induced hearing loss, but the weighing of involved variables has been subjective.
      Identification of patient and treatment characteristics to predict the absolute
      posttreatment hearing level is important for effective counseling of patients
      undergoing chemoradiotherapy. OBJECTIVE: To predict treatment-induced hearing
      loss among patients with head and neck cancer. DESIGN, SETTING, AND PARTICIPANTS:
      A retrospective cohort study was performed at The Netherlands Cancer Institute.
      One hundred and fifty-six patients with head and neck cancer treated with
      concomitant chemoradiotherapy as the primary treatment modality from January 1,
      1997, through December 31, 2011, were enrolled. Follow-up was complete on March
      1, 2012, and data were analyzed from April 1, 2011, through November 5, 2013.
      INTERVENTIONS: High-dose intravenously administered cisplatin-based concomitant
      chemoradiotherapy. Cisplatin, 100 mg/m2, was administered in 3 courses on days 1,
      22, and 43 during 7 weeks of radiotherapy (total radiation dose, 70 Gy in 35
      fractions). MAIN OUTCOMES AND MEASURES: Posttreatment bone conduction hearing
      threshold at pure-tone average frequencies of 1, 2, and 4 kHz, based on pure-tone
      audiometry after completion of treatment. Predictors included baseline hearing
      levels, radiation dose to the cochlea, and cisplatin dose. A multilevel mixed
      effects linear regression model for predicting whether or not posttreatment
      hearing was at least 35 dB was established, and cross-validated sensitivity and
      specificity were obtained. RESULTS: Of 156 patients who received high-dose
      concomitant chemoradiotherapy, 15 were missing the exact radiation dose to the
      cochlea and 41 had no data on posttreatment pure-tone audiometry. Nineteen
      patients had a hearing level of at least 35 dB for at least 1 ear before the
      treatment. The remaining 81 patients (162 ears) had a total cumulative cisplatin
      dose ranging from 315 to 600 (median, 546) mg. The radiation dose to the cochlea
      ranged from 1.1 to 70.9 (median, 13.6) Gy. Based on data from the 81 patients
      (162 ears), the area under the receiver operating characteristic curve was 0.68,
      with a sensitivity of 29% (95% CI, 13%-51%) and a specificity of 97% (95% CI, 88%
      100%), resulting in a positive predictive value of 78%. CONCLUSIONS AND
      RELEVANCE: Patient and treatment characteristics can be used to predict hearing
      level after concomitant chemoradiotherapy for head and neck cancer. This step may
      constitute the first in evidence-based individual counseling for treatment
      induced hearing loss.

PMID- 26291151
TI  - Unravelling Spinal Circuits of Pain and Mechanical Allodynia.
AB  - How do spinal circuits mediating tactile sensation and pain get entangled to
      evoke allodynia, i.e., pain sensation, in response to a normally innocuous
      stimulus? Recent breakthroughs are now closing this long-standing, critical gap.
      VGLUT3-expressing neurons and their polysynaptic connectivity to calretinin
      expressing neurons are now identified as key determinants of the spinal circuitry
      underlying mechanical allodynia. 

PMID- 26291152
TI  - Synchronous Spikes Are More Effective (but Not for Long).
AB  - The efficacy of spiking synchrony in corticocortical communication is poorly
      understood. A new study (Zandvakili and Kohn, 2015) in this issue provides
      compelling evidence that synchrony in a source population is not efficacious
      beyond the input layers of the target population. 

PMID- 26291153
TI  - It All Depends on the Context, but Also on the Amygdala.
AB  - Behavioral flexibility requires the brain to maintain and rely on cognitive
      contexts for dictating appropriate responses. Saez et al. (2015) demonstrate that
      such abstract rule-based representations co-exist in prefrontal cortices and in
      the amygdala, with the latter being surprisingly crucial for correct performance.

PMID- 26291154
TI  - Information Storage and Executive Control May Not Be So Separate after All.
AB  - Prefrontal cortex has been considered to implement processes such as attention,
      which control information stored elsewhere. In this issue of Neuron, Ester et al.
      (2015) demonstrate it also stores precise stimulus-specific information,
      questioning assumed neuroanatomical distinctions between storage and control.

PMID- 26291157
TI  - Translational Perspectives for Computational Neuroimaging.
AB  - Functional neuroimaging has made fundamental contributions to our understanding
      of brain function. It remains challenging, however, to translate these advances
      into diagnostic tools for psychiatry. Promising new avenues for translation are
      provided by computational modeling of neuroimaging data. This article reviews
      contemporary frameworks for computational neuroimaging, with a focus on forward
      models linking unobservable brain states to measurements. These approaches
      biophysical network models, generative models, and model-based fMRI analyses of
      neuromodulation-strive to move beyond statistical characterizations and toward
      mechanistic explanations of neuroimaging data. Focusing on schizophrenia as a
      paradigmatic spectrum disease, we review applications of these models to
      psychiatric questions, identify methodological challenges, and highlight trends
      of convergence among computational neuroimaging approaches. We conclude by
      outlining a translational neuromodeling strategy, highlighting the importance of
      openly available datasets from prospective patient studies for evaluating the
      clinical utility of computational models. 

PMID- 26291156
TI  - Altered Neuronal and Circuit Excitability in Fragile X Syndrome.
AB  - Fragile X syndrome (FXS) results from a genetic mutation in a single gene yet
      produces a phenotypically complex disorder with a range of neurological and
      psychiatric problems. Efforts to decipher how perturbations in signaling pathways
      lead to the myriad alterations in synaptic and cellular functions have provided
      insights into the molecular underpinnings of this disorder. From this large body
      of data, the theme of circuit hyperexcitability has emerged as a potential
      explanation for many of the neurological and psychiatric symptoms in FXS. The
      mechanisms for hyperexcitability range from alterations in the expression or
      activity of ion channels to changes in neurotransmitters and receptors.
      Contributions of these processes are often brain region and cell type specific,
      resulting in complex effects on circuit function that manifest as altered
      excitability. Here, we review the current state of knowledge of the molecular,
      synaptic, and circuit-level mechanisms underlying hyperexcitability and their
      contributions to the FXS phenotypes. 

PMID- 26291158
TI  - Regulatory Logic of Pan-Neuronal Gene Expression in C. elegans.
AB  - While neuronal cell types display an astounding degree of phenotypic diversity,
      most if not all neuron types share a core panel of terminal features. However,
      little is known about how pan-neuronal expression patterns are genetically
      programmed. Through an extensive analysis of the cis-regulatory control regions
      of a battery of pan-neuronal C. elegans genes, including genes involved in
      synaptic vesicle biology and neuropeptide signaling, we define a common
      organizational principle in the regulation of pan-neuronal genes in the form of a
      surprisingly complex array of seemingly redundant, parallel-acting cis-regulatory
      modules that direct expression to broad, overlapping domains throughout the
      nervous system. These parallel-acting cis-regulatory modules are responsive to a
      multitude of distinct trans-acting factors. Neuronal gene expression programs
      therefore fall into two fundamentally distinct classes. Neuron-type-specific
      genes are generally controlled by discrete and non-redundantly acting regulatory
      inputs, while pan-neuronal gene expression is controlled by diverse, coincident
      and seemingly redundant regulatory inputs. 

PMID- 26291155
TI  - Excitatory/Inhibitory Balance and Circuit Homeostasis in Autism Spectrum
      Disorders.
AB  - Autism spectrum disorders (ASDs) and related neurological disorders are
      associated with mutations in many genes affecting the ratio between neuronal
      excitation and inhibition. However, understanding the impact of these mutations
      on network activity is complicated by the plasticity of these networks, making it
      difficult in many cases to separate initial deficits from homeostatic
      compensation. Here we explore the contrasting evidence for primary defects in
      inhibition or excitation in ASDs and attempt to integrate the findings in terms
      of the brain's ability to maintain functional homeostasis. 

PMID- 26291159
TI  - The Intracellular Domain of the Frazzled/DCC Receptor Is a Transcription Factor
      Required for Commissural Axon Guidance.
AB  - In commissural neurons of Drosophila, the conserved Frazzled (Fra)/Deleted in
      Colorectal Cancer (DCC) receptor promotes midline axon crossing by signaling
      locally in response to Netrin and by inducing transcription of commissureless
      (comm), an antagonist of Slit-Roundabout midline repulsion, through an unknown
      mechanism. Here, we show that Fra is cleaved to release its intracellular domain
      (ICD), which shuttles between the cytoplasm and the nucleus, where it functions
      as a transcriptional activator. Rescue and gain-of-function experiments
      demonstrate that the Fra ICD is sufficient to regulate comm expression and that
      both gamma-secretase proteolysis of Fra and Fra's function as a transcriptional
      activator are required for its ability to regulate comm in vivo. Our data uncover
      an unexpected role for the Fra ICD as a transcription factor whose activity
      regulates the responsiveness of commissural axons at the midline and raise the
      possibility that nuclear signaling may be a common output of axon guidance
      receptors. 

PMID- 26291160
TI  - The Sorting Receptor SorCS1 Regulates Trafficking of Neurexin and AMPA Receptors.
AB  - The formation, function, and plasticity of synapses require dynamic changes in
      synaptic receptor composition. Here, we identify the sorting receptor SorCS1 as a
      key regulator of synaptic receptor trafficking. Four independent proteomic
      analyses identify the synaptic adhesion molecule neurexin and the AMPA glutamate
      receptor (AMPAR) as major proteins sorted by SorCS1. SorCS1 localizes to early
      and recycling endosomes and regulates neurexin and AMPAR surface trafficking.
      Surface proteome analysis of SorCS1-deficient neurons shows decreased surface
      levels of these, and additional, receptors. Quantitative in vivo analysis of
      SorCS1-knockout synaptic proteomes identifies SorCS1 as a global trafficking
      regulator and reveals decreased levels of receptors regulating adhesion and
      neurotransmission, including neurexins and AMPARs. Consequently, glutamatergic
      transmission at SorCS1-deficient synapses is reduced due to impaired AMPAR
      surface expression. SORCS1 mutations have been associated with autism and
      Alzheimer disease, suggesting that perturbed receptor trafficking contributes to
      synaptic-composition and -function defects underlying synaptopathies. 

PMID- 26291161
TI  - Neuroligins Sculpt Cerebellar Purkinje-Cell Circuits by Differential Control of
      Distinct Classes of Synapses.
AB  - Neuroligins are postsynaptic cell-adhesion molecules that bind presynaptic
      neurexins and are genetically linked to autism. Neuroligins are proposed to
      organize synaptogenesis and/or synaptic transmission, but no systematic analysis
      of neuroligins in a defined circuit is available. Here, we show that conditional
      deletion of all neuroligins in cerebellar Purkinje cells caused loss of distal
      climbing-fiber synapses and weakened climbing-fiber but not parallel-fiber
      synapses, consistent with alternative use of neuroligins and cerebellins as
      neurexin ligands for the excitatory climbing-fiber versus parallel-fiber
      synapses. Moreover, deletion of neuroligins increased the size of inhibitory
      basket/stellate-cell synapses but simultaneously severely impaired their
      function. Multiple neuroligin isoforms differentially contributed to climbing
      fiber and basket/stellate-cell synapse functions, such that inhibitory synapse
      specific neuroligin-2 was unexpectedly essential for maintaining normal climbing
      fiber synapse numbers. Using systematic analyses of all neuroligins in a defined
      neural circuit, our data thus show that neuroligins differentially contribute to
      various Purkinje-cell synapses in the cerebellum in vivo. 

PMID- 26291162
TI  - Dorsal Horn Circuits for Persistent Mechanical Pain.
AB  - Persistent mechanical hypersensitivity that occurs in the setting of injury or
      disease remains a major clinical problem largely because the underlying neural
      circuitry is still not known. Here we report the functional identification of key
      components of the elusive dorsal horn circuit for mechanical allodynia. We show
      that the transient expression of VGLUT3 by a discrete population of neurons in
      the deep dorsal horn is required for mechanical pain and that activation of the
      cells in the adult conveys mechanical hypersensitivity. The cells, which receive
      direct low threshold input, point to a novel location for circuit initiation.
      Subsequent analysis of c-Fos reveals the circuit extends dorsally to nociceptive
      lamina I projection neurons, and includes lamina II calretinin neurons, which we
      show also convey mechanical allodynia. Lastly, using inflammatory and neuropathic
      pain models, we show that multiple microcircuits in the dorsal horn encode this
      form of pain.

PMID- 26291163
TI  - A Temporary Gating of Actin Remodeling during Synaptic Plasticity Consists of the
      Interplay between the Kinase and Structural Functions of CaMKII.
AB  - The structural modification of dendritic spines plays a critical role in synaptic
      plasticity. CaMKII is a pivotal molecule involved in this process through both
      kinase-dependent and independent structural functions, but the respective
      contributions of these two functions to the synaptic plasticity remain unclear.
      We demonstrate that the transient interplay between the kinase and structural
      functions of CaMKII during the induction of synaptic plasticity temporally gates
      the activity-dependent modification of the actin cytoskeleton. Inactive CaMKII
      binds F-actin, thereby limiting access of actin-regulating proteins to F-actin
      and stabilizing spine structure. CaMKII-activating stimuli trigger dissociation
      of CaMKII from F-actin through specific autophosphorylation reactions within the
      F-actin binding region and permits F-actin remodeling by regulatory proteins
      followed by reassociation and restabilization. Blocking the autophosphorylation
      impairs both functional and structural plasticity without affecting kinase
      activity. These results underpin the importance of the interplay between the
      kinase and structural functions of CaMKII in defining a time window permissive
      for synaptic plasticity.

PMID- 26291164
TI  - Coordinated Neuronal Activity Enhances Corticocortical Communication.
AB  - Relaying neural signals between cortical areas is central to cognition and
      sensory processing. The temporal coordination of activity in a source population
      has been suggested to determine corticocortical signaling efficacy, but others
      have argued that coordination is functionally irrelevant. We reasoned that if
      coordination significantly influenced signaling, spiking in downstream networks
      should be preceded by transiently elevated coordination in a source population.
      We developed a metric to quantify network coordination in brief epochs, and
      applied it to simultaneous recordings of neuronal populations in cortical areas
      V1 and V2 of the macaque monkey. Spiking in the input layers of V2 was preceded
      by brief epochs of elevated V1 coordination, but this was not the case in other
      layers of V2. Our results indicate that V1 coordination influences its signaling
      to direct downstream targets, but that coordinated V1 epochs do not propagate
      through multiple downstream networks as in some corticocortical signaling
      schemes. 

PMID- 26291165
TI  - Structured Variability in Purkinje Cell Activity during Locomotion.
AB  - The cerebellum is a prominent vertebrate brain structure that is critically
      involved in sensorimotor function. During locomotion, cerebellar Purkinje cells
      are rhythmically active, shaping descending signals and coordinating commands
      from higher brain areas with the step cycle. However, the variation in this
      activity across steps has not been studied, and its statistical structure,
      afferent mechanisms, and relationship to behavior remain unknown. Here, using
      multi-electrode recordings in freely moving rats, we show that behavioral
      variables systematically influence the shape of the step-locked firing rate. This
      effect depends strongly on the phase of the step cycle and reveals a functional
      clustering of Purkinje cells. Furthermore, we find a pronounced disassociation
      between patterns of variability driven by the parallel and climbing fibers. These
      results suggest that Purkinje cell activity not only represents step phase within
      each cycle but also is shaped by behavior across steps, facilitating control of
      movement under dynamic conditions. 

PMID- 26291166
TI  - Habit Learning by Naive Macaques Is Marked by Response Sharpening of Striatal
      Neurons Representing the Cost and Outcome of Acquired Action Sequences.
AB  - Over a century of scientific work has focused on defining the factors motivating
      behavioral learning. Observations in animals and humans trained on a wide range
      of tasks support reinforcement learning (RL) algorithms as accounting for the
      learning. Still unknown, however, are the signals that drive learning in naive,
      untrained subjects. Here, we capitalized on a sequential saccade task in which
      macaque monkeys acquired repetitive scanning sequences without instruction. We
      found that spike activity in the caudate nucleus after each trial corresponded to
      an integrated cost-benefit signal that was highly correlated with the degree of
      naturalistic untutored learning by the monkeys. Across learning, neurons encoding
      both cost and outcome gradually acquired increasingly sharp phasic trial-end
      responses that paralleled the development of the habit-like, repetitive saccade
      sequences. Our findings demonstrate an integrated cost-benefit signal by which RL
      and its neural correlates could drive naturalistic behaviors in freely behaving
      primates.

PMID- 26291168
TI  - Short-Term Memory for Space and Time Flexibly Recruit Complementary Sensory
      Biased Frontal Lobe Attention Networks.
AB  - The frontal lobes control wide-ranging cognitive functions; however, functional
      subdivisions of human frontal cortex are only coarsely mapped. Here, functional
      magnetic resonance imaging reveals two distinct visual-biased attention regions
      in lateral frontal cortex, superior precentral sulcus (sPCS) and inferior
      precentral sulcus (iPCS), anatomically interdigitated with two auditory-biased
      attention regions, transverse gyrus intersecting precentral sulcus (tgPCS) and
      caudal inferior frontal sulcus (cIFS). Intrinsic functional connectivity analysis
      demonstrates that sPCS and iPCS fall within a broad visual-attention network,
      while tgPCS and cIFS fall within a broad auditory-attention network.
      Interestingly, we observe that spatial and temporal short-term memory (STM),
      respectively, recruit visual and auditory attention networks in the frontal lobe,
      independent of sensory modality. These findings not only demonstrate that both
      sensory modality and information domain influence frontal lobe functional
      organization, they also demonstrate that spatial processing co-localizes with
      visual processing and that temporal processing co-localizes with auditory
      processing in lateral frontal cortex. 

PMID- 26291169
TI  - Evaluation of Improvement in Nasal Obstruction Following Nasal Valve Correction
      in Patients With a History of Failed Septoplasty.
AB  - IMPORTANCE: Patients with a septal deviation and concerns about nasal obstruction
      often undergo septoplasty to improve nasal airflow. Following primary
      septoplasty, however, some patients have persistent symptoms due to nasal valve
      dysfunction and may require nasal valve surgery. OBJECTIVES: To evaluate the
      change in disease-specific quality of life for patients who undergo nasal valve
      correction after failed septoplasty using the Nasal Obstruction Symptom
      Evaluation (NOSE) survey and to determine whether identifiable anatomical risk
      factors are more common in patients with a history of failed septoplasty. DESIGN,
      SETTING, AND PARTICIPANTS: Prospective observational outcomes study conducted at
      a tertiary care medical center. Forty patients who underwent nasal valve
      correction through an open approach from January 1, 2012, through December 31,
      2014, with a history of septoplasty for nasal obstruction were included. Data
      analysis was conducted from January 1, 2013, through May 1, 2015. [corrected].
      INTERVENTIONS: Demographic information, a standardized nasal examination, and
      preoperative and postoperative NOSE scores were collected and reviewed. MAIN
      OUTCOMES AND MEASURES: Comparison between preoperative and postoperative NOSE
      scores at 2, 4, and more than 6 months after surgery. RESULTS: Forty patients
      were included in the study; 23 (57%) were male and 17 (43%) were female. The mean
      age was 39.3 years. Findings from preoperative nasal examination demonstrated
      moderate or severe internal nasal valve narrowing in 38 (95%) patients, internal
      nasal valve collapse in 19 (48%), external nasal valve narrowing in 18 (45%), or
      external nasal valve collapse in 16 (40%). The most common anatomical cause of
      obstruction was internal nasal valve narrowing in 38 (95%) patients, dorsal
      septum deflection in 26 (65%), and narrowed middle vault in 16 (40%). The mean
      (SD) preoperative NOSE score was 75.7 (20.1). Mean (SD) postoperative NOSE scores
      at 2, 4, and greater than 6 months were 31.4 (27.2), 34.0 (19.8), and 22.1
      (18.8), respectively, with significantly improved NOSE scores at each time point
      compared with before surgery (P < .001). CONCLUSIONS AND RELEVANCE: Nasal valve
      dysfunction remains an underdiagnosed entity and should be considered in all
      patients with septal deviation before septoplasty, especially in patients with a
      severe dorsal deflection and a narrow middle vault. In this study, surgical nasal
      valve correction demonstrated a significant reduction in nasal obstruction, as
      measured by a validated outcome measure, in patients for whom a previous
      septoplasty had failed. LEVEL OF EVIDENCE: 4.

PMID- 26291167
TI  - Abstract Context Representations in Primate Amygdala and Prefrontal Cortex.
AB  - Neurons in prefrontal cortex (PFC) encode rules, goals, and other abstract
      information thought to underlie cognitive, emotional, and behavioral flexibility.
      Here we show that the amygdala, a brain area traditionally thought to mediate
      emotions, also encodes abstract information that could underlie this flexibility.
      Monkeys performed a task in which stimulus-reinforcement contingencies varied
      between two sets of associations, each defining a context. Reinforcement
      prediction required identifying a stimulus and knowing the current context.
      Behavioral evidence indicated that monkeys utilized this information to perform
      inference and adjust their behavior. Neural representations in both amygdala and
      PFC reflected the linked sets of associations implicitly defining each context, a
      process requiring a level of abstraction characteristic of cognitive operations.
      Surprisingly, when errors were made, the context signal weakened substantially in
      the amygdala. These data emphasize the importance of maintaining abstract
      cognitive information in the amygdala to support flexible behavior. 

PMID- 26291171
TI  - A mathematical model for apoptotic switch in Drosophila.
AB  - Apoptosis is an evolutionarily-conserved process of autonomous cell death. The
      molecular switch mechanism underlying the fate decision of apoptosis in mammalian
      cells has been intensively studied by mathematical modeling. In contrast, the
      apoptotic switch in invertebrates, with highly conserved signaling proteins and
      pathway, remains poorly understood mechanistically and calls for theoretical
      elucidation. In this study, we develop a mathematical model of the apoptosis
      pathway in Drosophila and compare the switch mechanism to that in mammals.
      Enumeration of the elementary reactions for the model demonstrates that the
      molecular interactions among the signaling components are considerably different
      from their mammalian counterparts. A notable distinction in network organization
      is that the direct positive feedback from the effector caspase (EC) to the
      initiator caspase in mammalian pathway is replaced by a double-negative
      regulation in Drosophila. The model is calibrated by experimental input-output
      relationship and the simulated trajectories exhibit all-or-none bimodal behavior.
      Bifurcation diagrams confirm that the model of Drosophila apoptotic switch
      possesses bistability, a well-recognized feature for an apoptosis system. Since
      the apoptotic protease activating factor-1 (APAF1) induced irreversible
      activation of caspase is an essential and beneficial property for the mammalian
      apoptotic switch, we perform analysis of the bistable caspase activation with
      respect to the input of DARK protein, the Drosophila homolog of APAF1.
      Interestingly, this bistable behavior in Drosophila is predicted to be
      reversible. Further analysis suggests that the mechanism underlying the systems
      property of reversibility is the double-negative feedback from the EC to the
      initiator caspase. Using theoretical modeling, our study proposes plausible
      evolution of the switch mechanism for apoptosis between organisms. 

PMID- 26291170
TI  - Ilex latifolia Prevents Amyloid beta Protein (25-35)-Induced Memory Impairment by
      Inhibiting Apoptosis and Tau Phosphorylation in Mice.
AB  - Ilex latifolia Thunb. (Aquifoliaceae), a Chinese bitter tea called "kudingcha,"
      has been widely consumed as a health beverage and found to possess antioxidant,
      antidiabetic, antihypertensive, anti-inflammatory, and anti-ischemic activities.
      The aim of the present study was to investigate the neuroprotective effects of an
      ethanol extract of I. latifolia against amyloid beta protein (Abeta)-induced
      memory impairment in mice and neurotoxicity in cultured rat cortical neurons.
      Memory impairment in mice was induced by intracerebroventricular injection of 15
      nmol Abeta (25-35) and measured by the passive avoidance test and Morris water
      maze test. Chronic administration of I. latifolia (25-100 mg/kg, p.o.)
      significantly prevented Abeta (25-35)-induced memory loss. I. latifolia also
      prevented the decrease of glutathione concentrations, increased lipid
      peroxidation, expression of phosphorylated tau (p-tau), and changes in apoptosis
      associated proteins in the memory-impaired mouse brain. Exposure of cultured
      cortical neurons to 10 MUM Abeta (25-35) for 36 h induced neuronal apoptotic
      death. The neuronal cell death, elevation of intracellular Ca(2+) concentration,
      generation of reactive oxygen species, and expression of proapoptotic proteins
      caused by Abeta (25-35) in the cultured neurons were inhibited by treatment with
      I. latifolia (1-50 MUg/mL). These results suggest that I. latifolia may have a
      possible therapeutic role in managing cognitive impairment associated with
      Alzheimer's disease. The underlying mechanism might involve the antiapoptotic
      effects mediated by antioxidant activity and inhibition of p-tau formation.

PMID- 26291172
TI  - The effect of structural dimensionality on the electrocatalytic properties of the
      nickel selenide phase.
AB  - Nickel selenide (NiSe) nanostructures possessing different morphologies of wires,
      spheres and hexagons are synthesized by varying the selenium precursors,
      selenourea, selenium dioxide (SeO2) and potassium selenocyanate (KSeCN),
      respectively, and are characterized using X-ray diffraction, X-ray photoelectron
      spectroscopy, Raman spectroscopy, transmission electron microscopy and scanning
      electron microscopy techniques. Electrical measurements of a single nanowire and
      a hexagon carried out on devices fabricated by the focused ion beam (FIB)
      technique depict the semiconducting nature of NiSe and its ability to act as a
      visible light photodetector. The three different morphologies are used as
      catalysts for hydrogen evolution (HER), oxygen reduction (ORR) and glucose
      oxidation reactions. The wire morphology is found to be better than that of
      spheres and hexagons for all the reactions. Among the reactions studied, NiSe is
      found to be good for HER and glucose oxidation while ORR seems to terminate at
      the peroxide stage. 

PMID- 26291173
TI  - Filovirus RNA in Fruit Bats, China.

PMID- 26291174
TI  - A catalytic hydroesterification process using HCO2Na, Ru3(CO)12 and alcohols for
      the preparation of ester modified polybutadienes.
AB  - A method for the transition metal catalyzed modification of polybutadiene was
      developed. Specifically, reactions of polybutadiene with alcohols and sodium
      formate in the presence of Ru3(CO)12 and 2-pyridinemethanol produce ester
      derivatives of polybutadiene. By using this approach, selected ratios of mixed
      ester derivatives of polybutadiene can be produced by employing the corresponding
      ratio of alcohols. 

PMID- 26291175
TI  - Paley's watchmaker analogy and prebiotic synthetic chemistry in surfactant
      assemblies. Formaldehyde scavenging by pyrroles leading to porphyrins as a case
      study.
AB  - The formation of elaborate molecules is regarded as an essential first step in
      prebiotic chemistry, but how such transformations could spontaneously occur,
      particularly in dilute aqueous conditions, remains poorly understood. Here,
      micromolar concentrations of a 3,4-dialkylpyrrole and excess formaldehyde in
      aqueous micellar solution (pH 7) at 25 or 50  degrees C were found to give good
      yield (up to 40%) of the lipophilic octaalkylporphyrin. The reaction occurs
      despite a mean occupancy number of ~0.1 pyrrole molecules/micelle, and <1 of
      10,000 micelles initially containing the requisite 4 pyrrole molecules to form
      the porphyrin assuming a (random) Poisson distribution. Yields of up to 13% were
      observed in large, unilamellar phosphatidylcholine vesicles, wherein there are
      ~15,000 pyrrole molecules per vesicle membrane. Double-labeling crossover
      experiments (of 3,4-diethylpyrrole and 3,4-dimethylpyrrole) examined by mass
      spectrometry revealed facile exchange processes of reactive constituents among
      both micelle and vesicle surfactant assemblies. Together, the exchange of
      pyrrolic reactants among micelles and the thermodynamic driving force for
      tetrapyrrole formation overcome the apparent statistical odds against reaction.
      The fruitful exchange, accumulation and reaction of minute quantities of
      reactants in aqueous-surfactant assemblies suggest a general means for formation
      of prebiotically valuable constituents, even when the statistical odds at the
      outset are overwhelmingly improbable.

PMID- 26291176
TI  - Chitosan, Carbon Quantum Dot, and Silica Nanoparticle Mediated dsRNA Delivery for
      Gene Silencing in Aedes aegypti: A Comparative Analysis.
AB  - In spite of devastating impact of mosquito borne pathogens on humans, widespread
      resistance to chemical insecticides and environmental concerns from residual
      toxicity limit mosquito control strategies. We tested three nanoparticles,
      chitosan, carbon quantum dot (CQD), and silica complexed with dsRNA, to target
      two mosquito genes (SNF7 and SRC) for controlling Aedes aegypti larvae. Relative
      mRNA levels were quantified using qRT-PCR to evaluate knockdown efficiency in
      nanoparticle-dsRNA treated larvae. The knockdown efficiency of target genes
      correlated with dsRNA mediated larval mortality. Among the three nanoparticles
      tested, CQD was the most efficient carrier for dsRNA retention, delivery, and
      thereby causing gene silencing and mortality in Ae. aegypti. 

PMID- 26291177
TI  - Constipation Prophylaxis Is Rare for Adults Prescribed Outpatient Opioid Therapy
      From U.S. Emergency Departments.
AB  - OBJECTIVES: Constipation is a common and potentially serious side effect of oral
      opioids. Accordingly, most clinical guidelines suggest routine use of laxatives
      to prevent opioid-induced constipation. The objective was to characterize
      emergency provider prescribing of laxatives to prevent constipation among adults
      initiating outpatient opioid treatment. METHODS: National Hospital Ambulatory
      Medical Care Survey (NHAMCS) data from 2010 were analyzed. Among visits by
      individuals aged 18 years and older discharged from the emergency department (ED)
      with opioid prescriptions, the authors estimated the survey-weighted proportion
      of visits in which laxatives were also prescribed. A subgroup analysis was
      conducted for individuals aged 65 years and older, as the potential risks
      associated with opioid-induced constipation are greater among older individuals.
      To examine a group expected to be prescribed laxative medication and confirm that
      NHAMCS captures prescriptions for these medications, the authors estimated the
      proportion of visits by individuals discharged with prescriptions for laxatives
      among those who presented with constipation. RESULTS: Among visits in 2010 by
      adults aged 18 years and older discharged from the ED with opioid prescriptions,
      0.9% (95% confidence interval [CI] = 0.7% to 1.3%, estimated total n = 191,203
      out of 21,075,050) received prescriptions for laxatives. Among the subset of
      visits by adults aged 65 years and older, 1.0% (95% CI = 0.5% to 2.0%, estimated
      total n = 18,681 out of 1,904,411) received prescriptions for laxatives. In
      comparison, among visits by individuals aged 18 years and older with constipation
      as a reason for visit, 42% received prescriptions for laxatives. CONCLUSIONS: In
      this nationally representative sample, laxatives were not routinely prescribed to
      adults discharged from the ED with prescriptions for opioid pain medications.
      Routine prescribing of laxatives for ED visits may improve the safety and
      effectiveness of outpatient opioid pain management.

PMID- 26291178
TI  - Shared health characteristics in Hispanic colorectal cancer patients and their
      primary social support person following primary diagnosis.
AB  - PURPOSE: The aim of this paper was to determine individual and shared levels of
      psychosocial, behavioral, and symptomological health characteristics among
      Hispanics with recent history of cancer and their primary social support person
      (PSSP) in the years following diagnosis. PATIENTS AND METHODS: Recruited from a
      population-based cohort study were 409 Hispanic patients with a previous
      diagnosis of colorectal cancer. Forty-seven patients identified a PSSP, who
      assists with medical decision-making and health-related matters, who also
      participated in the study. Current behavioral (smoking, alcohol use, physical
      activity, and complementary and alternative medicine use), psychosocial (stress
      and mindfulness), and physical symptom (fatigue) data were obtained using
      validated instruments. Analyses tested the individual and shared (between
      patients and PSSPs) variance in these health measures. RESULTS: The sample was
      diagnosed on average 3.1 years (standard deviation = 1.7) prior to assessment.
      PSSPs were mainly spouses/partners (63%) or children (28%) of patients. Among
      patients, stress was positively associated with being a current smoker (p < 0.01)
      and with fatigue (r = 0.45, p < 0.001); stress was negatively correlated with
      mindfulness (r = -0.41, p < 0.001); mindfulness was negatively associated with
      smoking (odds ratio (OR) = 0.72, p < 0.01) and alcohol consumption (OR = 0.83, p
      < 0.05); the inverse relationship between mindfulness and fatigue was partially
      mediated through lower levels of stress (beta = -0.17, p < 0.001). Similar
      patterns were observed among PSSPs. Patient mindfulness was negatively correlated
      with PSSP stress (r = -0.45, p < 0.01). Complementary and alternative medicine
      use showed interdependence between patients and PSSPs for use of herbal remedies
      (OR = 6.2; p < 0.01) and bodywork (OR = 8.3, p < 0.05). CONCLUSION: Hispanic
      colorectal cancer patients and their PSSP share a common health milieu in the
      years following a cancer diagnosis, offering opportunities for advancing
      interpersonal intervention approaches in cancer care. Copyright (c) 2015 John
      Wiley & Sons, Ltd.

PMID- 26291179
TI  - Prevalence and Correlates of Psychological Symptoms in Chinese Doctors as
      Measured with the SCL-90-R: A Meta-Analysis.
AB  - Poor mental health in doctors appears to be a global phenomenon, but there are
      limited data on changes in doctors' psychological symptoms over time in mainland
      China. Through a detailed meta-analysis of cross-sectional studies, our aim was
      to examine the prevalence of psychological symptoms in Chinese physicians as
      measured with the Symptom Checklist 90-R (SCL-90-R) and to explore the factors
      associated with doctors' mental health. A comprehensive search was performed in
      major English and Chinese databases. Thirty studies involving a total of 6,099
      subjects were included in the meta-analysis. The pooled estimates of
      psychological symptoms including somatization, obsession-compulsion,
      interpersonal-sensitivity, depression, anxiety, hostility, phobic anxiety, and
      paranoid ideation among doctors were significantly higher than those in the
      general population. Only psychoticism was similar in prevalence to Chinese
      population norms. The prevalence increased with the study year but decreased with
      physicians' increasing age. Doctors from central and western China experienced
      more mental health symptoms than those from eastern China. Psychiatrists scored
      significantly less favorably than other doctors on most subscales of the SCL-90
      R. Doctors' mental health may be associated with age discrepancy, quantitative
      workload, effort-reward ratio, doctor-patient relationships, professional
      identity, and individual traits. To minimize the risk of poor mental health in
      doctors, screening and professional intervention services should be provided at
      early career stages to raise physicians' awareness about the importance of
      maintaining psychological well-being and to reduce the prevalence of
      psychological symptoms.

PMID- 26291180
TI  - Development of macitentan for the treatment of pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a serious, chronic condition that,
      without early recognition and treatment, leads to progressive right heart failure
      and death. The dual endothelin receptor antagonist macitentan was designed
      through a deliberate discovery process to maximize endothelin-axis blockade while
      improving adverse-effect profiles compared with previous compounds. Macitentan's
      efficacy was demonstrated in an event-driven morbidity and mortality study of
      treatment-naive and background PAH therapy-treated symptomatic patients. Compared
      to placebo, 10 mg of macitentan significantly reduced the relative risk of
      morbidity and mortality by 45%, primarily by delaying PAH worsening, most
      prominently in World Health Organization (WHO) functional class II and III PAH
      patients. Macitentan reduced the incidence of the composite end point of PAH
      related hospitalizations and mortality and improved WHO FC and exercise capacity
      (6-min walk distance). Furthermore, it significantly improved cardiopulmonary
      hemodynamics and quality of life, and had a favorable safety and tolerability
      profile. To date, this was the largest and longest prospective trial for PAH.
      Macitentan, currently the only approved oral PAH treatment shown to be safe and
      effective in delaying long-term progression and reducing PAH-related
      hospitalizations, has changed treatment paradigms from goal-directed to long-term
      outcome-oriented therapy. 

PMID- 26291181
TI  - Longitudinal evaluation of the natural history of conservatively managed
      nonfunctioning pituitary adenomas.
AB  - CONTEXT: The optimal management of nonfunctioning pituitary adenomas presenting
      without symptomatic mass effect remains uncertain. The objective of this study
      was to elucidate the natural history of nonfunctioning pituitary adenomas managed
      conservatively. DESIGN: Volumetric evaluation of tumour growth in serial
      pituitary MRI scans by a single observer and retrospective review of changes in
      pituitary function. PATIENTS: Patients with nonfunctioning pituitary adenomas who
      underwent at least 2 serial pituitary MRI scans over >=6 months between 2003 and
      2013 prior to any intervention. MEASUREMENTS: Primary end-point was a >=20%
      increase in volume or surgery. Secondary end-points were rate of pituitary
      dysfunction and pituitary apoplexy. RESULTS: Fifty nonfunctioning pituitary
      adenomas (23 macroadenomas and 27 microadenomas, mean age 49, range 17-85 years)
      were identified. Mean follow-up was 36 months (range 6-79). An increase in volume
      occurred in macroadenomas (P < 0.01) but not in microadenomas (P = 0.44). A >=20%
      increase in volume occurred in nine of 23 macroadenomas compared with two of 27
      microadenomas (P < 0.05). Five macroadenomas (one with new visual field defect)
      and one microadenoma proceeded to surgery (P = 0.08). Hormone deficiency was
      present in four of 24 macroadenomas vs 0 of 27 microadenomas (P < 0.05) at
      baseline, while new hormone deficiency developed in only two macroadenomas during
      follow-up. Pituitary apoplexy occurred in one microadenoma. A growth rate of >10
      mm3 /month assessed at approximately 2 years of follow-up among the macroadenoma
      group was highly predictive (sensitivity and specificity of 90%) of a >=20%
      increase in volume or surgery. CONCLUSIONS: Nonfunctioning pituitary
      macroadenomas have a greater tendency to grow and require surgical intervention
      while microadenomas rarely progress.

PMID- 26291182
TI  - Diabetic Ketoacidosis in a Patient with Type 2 Diabetes After Initiation of
      Sodium-Glucose Cotransporter 2 Inhibitor Treatment.
AB  - Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were recently introduced for
      the treatment of type 2 diabetes (T2D). SGLT2i lower plasma glucose by inhibiting
      the renal reuptake of glucose leading to glucosuria. Generally, these drugs are
      considered safe to use. However, recently, SGLT2i have been suggested to
      predispose to ketoacidosis. Here, we present a case of diabetic ketoacidosis
      (DKA) developed in an obese, poorly controlled male patient with T2D treated with
      the SGLT2i dapagliflozin. He was admitted with DKA 5 days after the initiation of
      treatment with the SGLT2i dapagliflozin. On admission, the primary symptoms were
      nausea and dizziness, and he was hypertensive (170/103) and tachycardic (119 bpm)
      and had mild hyperglycaemia (15.3 mmol/l), severe ketonuria and severe metabolic
      acidosis (pH 7.08). He responded well to infusions of insulin, glucose and saline
      and was discharged after 72 hr with insulin as the only glucose-lowering therapy.
      After 1 month, dapagliflozin was reintroduced as add-on to insulin with no
      recurrent signs of ketoacidosis. During acute illness or other conditions with
      increased insulin demands in diabetes, SGLT2i may predispose to the formation of
      ketone bodies and ensuing acidosis.

PMID- 26291183
TI  - Impact and hardness optimisation of composite materials inspired by the babassu
      nut (Orbignya speciosa).
AB  - The babassu nut is the fruit of the babassu palm Orbignya speciosa. The
      combination of hardness and impact strength is difficult to acquire for
      artificial materials, making the babassu nut a promising source for biomimetic
      inspiration. Unnotched Charpy impact tests, Shore D hardness tests and scanning
      electron microscopy were used for mechanical and microscopical analysis of the
      pericarp. Four major principles were found for a biomimetic approach: a hard core
      ((1); endocarp) is embedded in a soft outer layer of high impact strength ((2);
      epicarp) and is reinforced with fibres of variable fineness (3), some of which
      are oriented radial to the core (4). Biomimetic fibre-reinforced composites were
      produced using abstracted mechanisms of the babassu nut based on regenerated
      cellulose fibres (lyocell, L) with two different fineness values as reinforcement
      embedded in a polylactide (PLA) core matrix and polypropylene (PP) based outer
      layers. The biomimetic fibre composite reaches a significantly higher impact
      strength that is 1.6 times higher than the reference sample produced from a
      PLA/PP/L-blend. At the same time the hardness is slightly increased compared to
      PP/L. 

PMID- 26291184
TI  - Peritendinous elastase treatment induces tendon degeneration in rats: A potential
      model of tendinopathy in vivo.
AB  - The purpose of this study was to investigate the role of elastase on
      tendinopathy, as well as to evaluate the potential for peritendinous injections
      of elastase into rats to cause tendinopathy. We first investigated the expression
      of elastase in the tendons of patients with tendinopathy, and then established
      the effects of elastase injection on the Achilles tendons of rats.
      Ultrasonographic and incapacitance testing was used to conduct tests for 8 weeks.
      Tendon tissues were collected for histological observation and protein levels of
      collagen type I and type III were detected using Western blotting. The percentage
      of elastase-positive cells increased in human specimens with grades II and III
      tendinopathy. The rat model demonstrated that the thickness of the tendon
      increased after elastase injection during Week 2-8. Hypercellularity and focal
      lesions were detected after Week 2. The expression of elastase was increased and
      elastin was decreased in Week 8. Collagen type I expression was decreased, but
      type III was increased in Week 4. These results suggested that elastase may be
      involved in the development of chronic tendinopathy, and that peritendinous
      injection of elastase may result in tendinopathy in rats.

PMID- 26291185
TI  - The shorter, the better: A review of the evidence for a shorter contraceptive
      hormone-free interval.
AB  - OBJECTIVES: The menstrual cycle is characterised by cyclical fluctuations in
      oestrogens, progesterone and androgens. Changes in hormone levels in the
      premenstrual phase with the decline in progesterone trigger a physiological
      reaction which culminates in menstruation. This process is accompanied in many
      women by various symptoms such as pelvic pain, headache, mood disorders and
      gastrointestinal discomfort. The aim of this article was to summarise the latest
      findings on the physiology and pathophysiology of menstruation and review the
      impact of shortening the hormone-free interval (HFI) on the health and wellbeing
      of women. RESULTS: Menstruation can be viewed as an inflammatory event in which
      local and systemic effects produce symptoms in genital and extragenital regions
      of the body. The mast cells are the main mediator of this reaction. In women
      using hormonal contraceptives, menstrual bleeding is not biologically necessary
      and it may be advantageous to maintain more stable levels of oestrogens,
      progesterone and androgens throughout the cycle. New combined oral contraceptives
      (COCs) have been formulated with a progressively shorter HFI (24/4 and 26/2) than
      traditional 21/7 pills, with the rationale of reducing hormone withdrawal-
      associated symptoms. Several studies have shown the beneficial effects of these
      regimens, which reduce the inflammatory exposure of the female organism and thus
      have the capacity to increase the quality of life of women. A combination of
      estradiol valerate (E2V) and dienogest (DNG) is administered on the shortest 26/2
      regimen. This regimen has a broad evidence base from randomised controlled trials
      that have examined the impact of E2V/DNG on symptoms and quality of life.
      CONCLUSIONS: Shortening the HFI reduces the occurrence of bleeding-related
      inflammatory processes and subsequent physical and mental symptoms. The shortest
      interval with evidence of reproductive and sexual health benefits is provided by
      a 26/2 regimen.

PMID- 26291186
TI  - Richard Willstatter and the 1915 Nobel Prize in chemistry.
AB  - One hundred years after his Nobel Prize, Richard Willstatter's achievements and
      the fascinating role he played in 20th century chemistry are discussed in this
      Essay. Several of his discoveries, such as the anthocyanidins, cyclooctatetraene,
      the ortho-quinones, and the structure of cocaine, will forever be associated with
      his name. 

PMID- 26291187
TI  - Suspended Wavy Graphene Microribbons for Highly Stretchable Microsupercapacitors.
AB  - Highly stretchable microsupercapacitors with stable electrochemical performance
      are fabricated. Their excellent stretchable and electrochemical performance
      relies on the suspended wavy structures of graphene microribbons. This avoids the
      detachment and cracks of the electrode materials. In addition, it ensures the
      electrode fingers keep a relatively constant distance so the stability of the
      microsupercapacitors can be enhanced. 

PMID- 26291188
TI  - Social Determinants of Men's Health Disparities.

PMID- 26291189
TI  - The Interdependence of African American Men's Definitions of Manhood and Health.
AB  - In this article, we explore themes that cut across how 24- to 77-year-old African
      American men define manhood and health. Utilizing a thematic approach, we
      analyzed data from 9 focus groups (N = 73). We found that manhood and health were
      relational constructs that are interrelated in men's minds and experiences.
      Manhood and health were defined by the characteristics men embody, the behaviors
      men engage in, and the goals and values men had to positively influence their
      families and communities. Thus, manhood and health are interdependent constructs
      and their interrelationship should be considered in efforts to promote African
      American men's health. 

PMID- 26291190
TI  - Race, Social and Environmental Conditions, and Health Behaviors in Men.
AB  - Although understanding race differences in health behaviors among men is an
      important step in reducing disparities in leading causes of death in the United
      States, progress has been stifled when using national data because of the
      confounding of race, socioeconomic status, and residential segregation. The
      purpose of this study is to examine the nature of disparities in health behaviors
      among African American and white men in the Exploring Health Disparities in
      Integrated Communities Study-Southwest Baltimore, which was conducted in a
      racially integrated neighborhood of Baltimore to data from the 2003 National
      Health Interview Survey. After adjusting for age, marital status, insurance,
      income, educational attainment, poor or fair health, and obesity status, African
      American men in National Health Interview Survey had greater odds of being
      physically inactive (odds ratio [OR] = 1.48; 95% confidence interval [CI], 129
      1.69), reduced odds of being a current smoker (OR = 0.77; 95% CI, 0.65-0.90), and
      reduced odds of being a current drinker (OR = 0.58; 95% CI, 0.50-0.67). In the
      Exploring Health Disparities in Integrated Communities Study-Southwest Baltimore
      sample, African American and white men had similar odds of being physically
      inactive (OR = 0.79; 95% CI, 0.50-1.24), being a current smoker (OR = 0.86; 95%
      CI, 0.60-1.23), or being a current drinker (OR = 1.34; 95% CI, 0.81-2.21).
      Because race disparities in these health behaviors were ameliorated in the sample
      where African American and white men were living under similar social,
      environmental, and socioeconomic status conditions, these findings suggest that
      social environment may be an important determinant of health behaviors among
      African American and white men. Public health interventions and health promotion
      strategies should consider the social environment when seeking to better
      understand men's health disparities. 

PMID- 26291191
TI  - Racial/Ethnic Disparities in Men's Health: Examining Psychosocial Mechanisms.
AB  - This study uses data from the Health and Retirement Study and an approach
      informed by the Biopsychosocial Model of Racism as a Stressor to examine the
      extent to which socioeconomic status, stressors, discrimination, and neighborhood
      conditions are mechanisms underlying racial/ethnic disparities in functional
      limitations among men. Results reveal that racial/ethnic differences in
      socioeconomic status, stressors, discrimination, and neighborhood conditions
      individually and collectively-account for a substantial proportion of
      racial/ethnic disparities in functional limitations. Findings suggest that the
      social determinants of health for men of color need to be more seriously
      considered in investigations of and efforts to address health disparities. 

PMID- 26291192
TI  - Examining Place As a Social Determinant of Health: Association Between Diabetes
      and US Geographic Region Among Non-Hispanic Whites and a Diverse Group of
      Hispanic/Latino Men.
AB  - Place (geographic location), birthplace, the number of years in the United
      States, and gender are important social determinants of health essential to our
      understanding of health disparities. In this study, we examined the association
      between place and diabetes in white and Hispanic/Latino men and found that place
      and the number of years in the United States are important social determinants of
      health. Our findings provide implications for a nuanced perspective by
      highlighting the importance of examining social determinants of health to
      identify tailored interventions to address disparities in diabetes for diverse
      groups of Hispanic/Latino men. 

PMID- 26291193
TI  - Awareness, Attitudes, and Practices Related to Coronavirus Pandemic Among Public
      in Saudi Arabia.
AB  - New cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) were
      reported in Gulf countries in 2014, and to date, it has reportedly infected 837
      people and killed 291 globally. Awareness of an individual's knowledge and being
      able to predict his or her behavior is crucial when evaluating clinical
      preparedness for pandemics with a highly pathogenic virus. The aim of this study
      was to identify awareness, attitudes, and practices related to MERS-CoV among the
      public in Saudi Arabia. A cross-sectional study of 1147 adult subjects recruited
      from various shopping malls in Riyadh was conducted. All the subjects were
      interviewed using a questionnaire that tested their knowledge, attitudes, and use
      of precautionary measures in relation to the MERS-CoV pandemic. The majority of
      the participants showed high levels of concern and had utilized precautionary
      measures. After adjusting for other variables, gender was the only significant
      predictor of the level of concern (P < .001), while knowledge was the significant
      predictor of both the level of concern and precaution (P < .001). High concern
      translated into a higher compliance with precautionary recommendations. Frequent
      communication between health care providers and the public is recommended to help
      dispel myths about the disease and to empower the public with the information
      needed to help the Saudi government in containing the disease outbreak. 

PMID- 26291194
TI  - Incidence of Clinician-Diagnosed Lyme Disease, United States, 2005-2010.
AB  - National surveillance provides important information about Lyme disease (LD) but
      is subject to underreporting and variations in practice. Information is limited
      about the national epidemiology of LD from other sources. Retrospective analysis
      of a nationwide health insurance claims database identified patients from 2005
      2010 with clinician-diagnosed LD using International Classification of Diseases,
      Ninth Revision, Clinical Modification, codes and antimicrobial drug
      prescriptions. Of 103,647,966 person-years, 985 inpatient admissions and 44,445
      outpatient LD diagnoses were identified. Epidemiologic patterns were similar to
      US surveillance data overall. Outpatient incidence was highest among boys 5-9
      years of age and persons of both sexes 60-64 years of age. On the basis of
      extrapolation to the US population and application of correction factors for
      coding, we estimate that annual incidence is 106.6 cases/100,000 persons and that
      ~329,000 (95% credible interval 296,000-376,000) LD cases occur annually. LD is a
      major US public health problem that causes substantial use of health care
      resources. 

PMID- 26291195
TI  - Marked Strain-Specific Differences in the SU5416 Rat Model of Severe Pulmonary
      Arterial Hypertension.
AB  - We assessed the pulmonary hemodynamic response to vascular endothelial growth
      factor receptor, type 2, inhibition using SU5416 (SU) with and without chronic
      hypoxia (CH) in different background strains and colonies of rats. A single
      subcutaneous injection of SU (20 mg/kg) or vehicle was administered to different
      substrains of Sprague-Dawley (SD) rats, and they were compared with Lewis and
      Fischer rats, with and without exposure to CH (10% O2 for 3 wk). Remarkably, a
      unique colony of SD rats from Charles River Laboratories, termed the SD
      hyperresponsive type, exhibited severe pulmonary arterial hypertension (PAH) with
      SU alone, characterized by increased right ventricular systolic pressure, right
      ventricular/left ventricular plus septal weight ratio, and arteriolar occlusive
      lesions at 7-8 weeks (all P < 0.0001 versus vehicle). In contrast, the other SD
      substrain from Harlan Laboratories, termed SD-typical type, as well as Fischer
      rats, developed severe PAH only when exposed to SU and CH, whereas Lewis rats
      showed only a minimal response. All SD-typical type rats survived for up to 13
      weeks after SU/CH, whereas SD-hyperresponsive type rats exhibited mortality after
      SU and SU/CH (35% and 50%, respectively) at 8 weeks. Fischer rats exposed to
      SU/CH exhibited the greatest mortality at 8 weeks (78%), beginning as early as 4
      weeks after SU and preceded by right ventricle enlargement. Of note, a partial
      recovery of PAH after 8 weeks was observed in the SD-typical type substrain only.
      In conclusion, variation in strain, even between colonies of the same strain, has
      a remarkable influence on the nature and severity of the response to SU,
      consistent with an important role for genetic modifiers of the PAH phenotype. 

PMID- 26291198
TI  - Heterogeneous side chain conformation highlights a network of interactions
      implicated in hysteresis of the knotted protein, minimal tied trefoil.
AB  - Hysteresis is a signature for a bistability in the native landscape of a protein
      with significant transition state barriers for the interconversion of stable
      species. Large global stability, as in GFP, contributes to the observation of
      this rare hysteretic phenomenon in folding. The signature for such behavior is
      non-coincidence in the unfolding and refolding transitions, despite waiting
      significantly longer than the time necessary for complete denaturation. Our work
      indicates that hysteresis in the knotted protein, the minimal tied trefoil from
      Thermotoga maritma (MTTTm), is mediated by a network of side chain interactions
      within a tightly packed core. These initially identified interactions include
      proline 62 from a tight beta-like turn, phenylalanine 65 at the beginning of the
      knotting loop, and histidine 114 that initiates the threading element. It is this
      tightly packed region and the knotting element that we propose is disrupted with
      prolonged incubation in the denatured state, and is involved in the observed
      hysteresis. Interestingly, the disruption is not linked to backbone interactions,
      but rather to the packing of side chains in this critical region. 

PMID- 26291199
TI  - Selexipag: An Oral and Selective IP Prostacyclin Receptor Agonist for the
      Treatment of Pulmonary Arterial Hypertension.
AB  - Prostacyclin controls cardiovascular function via activation of the prostacyclin
      receptor. Decreased prostacyclin production occurs in several cardiovascular
      diseases. However, the clinical use of prostacyclin and its analogues is
      complicated by their chemical and metabolic instability. A medicinal chemistry
      program searched for novel nonprostanoid prostacyclin receptor agonists not
      subject to these limitations. A compound with a diphenylpyrazine structural core
      was synthesized. Metabolic stability and agonist potency were optimized through
      modification of the linear side chain. Compound 12b (MRE-269, ACT-333679) was
      identified as a potent and highly selective prostacyclin receptor agonist.
      Replacement of the terminal carboxyl group with an N-acylsulfonamide group
      yielded parent compound 26a (selexipag, NS-304, ACT-293987), which is orally
      active and provides sustained plasma exposure of 12b. Compound 26a was developed
      for the treatment of pulmonary arterial hypertension and shown to reduce the risk
      of the composite morbidity/mortality end point in a phase 3 event-driven clinical
      trial. 

PMID- 26291200
TI  - Compound-specific hydrogen isotope analysis of heteroatom-bearing compounds via
      gas chromatography-chromium-based high-temperature conversion (Cr/HTC)-isotope
      ratio mass spectrometry.
AB  - The traditional high-temperature conversion (HTC) approach toward compound
      specific stable isotope analysis (CSIA) of hydrogen for heteroatom-bearing (i.e.,
      N, Cl, S) compounds has been afflicted by fractionation bias due to formation of
      byproducts HCN, HCl, and H2S. This study presents a chromium-based high
      temperature conversion (Cr/HTC) approach for organic compounds containing
      nitrogen, chlorine, and sulfur. Following peak separation along a gas
      chromatographic (GC) column, the use of thermally stable ceramic Cr/HTC reactors
      at 1100-1500  degrees C and chemical sequestration of N, Cl, and S by chromium
      result in quantitative conversion of compound-specific organic hydrogen to H2
      analyte gas. The overall hydrogen isotope analysis via GC-Cr/HTC-isotope ratio
      mass spectrometry (IRMS) achieved a precision of better than +/- 5 mUr along the
      VSMOW-SLAP scale. The accuracy of GC-Cr/HTC-IRMS was validated with organic
      reference materials (RM) in comparison with online EA-Cr/HTC-IRMS and offline
      dual-inlet IRMS. The utility and reliability of the GC-Cr/HTC-IRMS system were
      documented during the routine measurement of more than 500 heteroatom-bearing
      organic samples spanning a delta(2)H range of -181 mUr to 629 mUr. 

PMID- 26291201
TI  - Catalytic Asymmetric [3 + 2] Cyclization Reactions of 3-Isothiocyanato Oxindoles
      and Alkynyl Ketones Via an in Situ Generated Magnesium Catalyst.
AB  - A highly enantioselective formal [3 + 2] cycloaddition reaction between 3
      isothiocyanato oxindoles and alkynyl ketones is reported for the first time. An
      oxazoline-OH type chiral ligand derived from o-hydroxy-phenylacetic acid is
      employed to generate an effective magnesium catalyst in the current cyclization
      reaction and give serials of chiral spirooxindoles with good chemical yields and
      enantioselectivities. 

PMID- 26291202
TI  - Covalent Linking Greatly Enhances Photoinduced Electron Transfer in Fullerene
      Quantum Dot Nanocomposites: Time-Domain Ab Initio Study.
AB  - Nonadiabatic molecular dynamics combined with time-domain density functional
      theory are used to study electron transfer (ET) from a CdSe quantum dot (QD) to
      the C60 fullerene, occurring in several types of hybrid organic/inorganic
      nanocomposites. By unveiling the time dependence of the ET process, we show that
      covalent bonding between the QD and C60 is particularly important to ensure
      ultrafast transmission of the excited electron from the QD photon-harvester to
      the C60 electron acceptor. Despite the close proximity of the donor and acceptor
      species provided by direct van der Waals contact, it leads to a notably weaker QD
      C60 interaction than a lengthy molecular bridge. We show that the ET rate in a
      nonbonded mixture of QDs and C60 can be enhanced by doping. The photoinduced ET
      is promoted primarily by mid- and low-frequency vibrations. The study establishes
      the basic design principles for enhancing photoinduced charge separation in
      nanoscale light harvesting materials. 

PMID- 26291203
TI  - (25)Mg Solid-State NMR: A Sensitive Probe of Adsorbing Guest Molecules on a Metal
      Center in Metal-Organic Framework CPO-27-Mg.
AB  - Metal-organic frameworks (MOFs) have excellent adsorption capability. To
      understand their adsorptive properties requires detailed information on the host
      guest interaction. The information on MOF desolvation (or activation) is also
      crucial because the very first step of many applications requires removal of the
      solvent molecules occluded inside of the pores. Unfortunately, such information
      is not always available from powder XRD data. Solid-state NMR is an excellent
      complementary technique to XRD. CPO-27-Mg is a MOF with unusual adsorption
      ability. The adsorption involves a direct interaction between Mg and guest
      species. Herein, we present, for the first time, a natural abundance (25)Mg solid
      state NMR study of CPO-27-Mg at an ultrahigh magnetic field of 21.1 T. The
      results provide new physical insights into the effects of dehydration/rehydration
      and adsorption of guest species on the Mg local environment. 

PMID- 26291204
TI  - Hydrogen Bonding and OH-Stretch Spectroscopy in Water: Hexamer (Cage), Liquid
      Surface, Liquid, and Ice.
AB  - We present a unified picture of how OH-stretch spectroscopy in water can be
      understood in terms of hydrogen bonding for the four systems listed in the title.
      To understand the strength, and hence OH-stretch frequency, of a hydrogen bond,
      it is crucial to consider the number of additional acceptor hydrogen bonds made
      by both the donor and acceptor molecules. This necessity for focusing on the
      hydrogen-bond environment of both donor and acceptor molecules follows from
      quantum chemical considerations and is related to the three-body interactions in
      water. Armed with this understanding we can make a detailed interpretation of the
      OH-stretch IR absorption spectrum of the cage conformer for HOD(D2O)5 and the
      imaginary part of the ssp OH-stretch sum-frequency spectrum of the surface of
      liquid D2O with dilute HOD. 

PMID- 26291205
TI  - Simulating Asymmetric Top Impurities in Superfluid Clusters: A para-Water Dopant
      in para-Hydrogen.
AB  - We present the first simulation study of bosonic clusters doped with an
      asymmetric top molecule. The path-integral Monte Carlo method with the latest
      methodological advance in treating rigid-body rotation [Noya, E. G.; Vega, C.;
      McBride, C. J. Chem. Phys.2011, 134, 054117] is employed to study a para-water
      impurity in para-hydrogen clusters with up to 20 para-hydrogen molecules. The
      growth pattern of the doped clusters is similar in nature to that of pure
      clusters. The para-water molecule appears to rotate freely in the cluster. The
      presence of para-water substantially quenches the superfluid response of para
      hydrogen with respect to the space-fixed frame. 

PMID- 26291206
TI  - Collisional Energy Transfer from Highly Vibrationally Excited Radicals Is Very
      Efficient.
AB  - Although highly vibrationally excited (HVE) radicals are ubiquitous in natural
      environments, the effect of collisional energy transfer (ET) on their reactivity
      has yet to be fully characterized. We have used time-resolved IR emission
      spectroscopy to characterize the vibrational-to-translational quenching of a
      small HVE radical, ketenyl (HCCO), by inert gases. Photolysis of ethyl ethynyl
      ether at 193 nm provides HVE HCCO in the X(2)A" electronic ground-state, with a
      nascent internal energy of 2.2 +/- 0.6 eV. IR emission is monitored as an
      indicator of vibrational energy, and spectral modeling allows direct
      determination of the average energy lost per collision as a function of the
      internal energy. Collisional deactivation of HVE HCCO is shown to be minimally an
      order of magnitude more efficient than closed-shell molecules of comparable size.
      Schwartz-Slawsky-Herzfeld-Tanczos (SSHT) theory, modified for HVE molecules,
      suggests that this ET enhancement is due to a strong attractive intermolecular
      interaction. 

PMID- 26291207
TI  - Functionalization of Oxide Surfaces through Reaction with 1,3-Dialkylimidazolium
      Ionic Liquids.
AB  - Practical applications of ionic liquids (ILs) often involve IL/oxide interfaces,
      but little is known regarding their interfacial chemistry. The unusual
      physicochemical properties of ILs, including their exceptionally low vapor
      pressure, provide access to such interfaces using a surface science approach in
      ultrahigh vacuum (UHV). We have applied synchrotron radiation photoelectron
      spectroscopy (SR-PES) to the study of a thin film of the ionic liquid
      [C6C1Im][Tf2N] prepared in situ in UHV on ordered stoichiometric CeO2(111) and
      partially reduced CeO2-x. On the partially reduced surface, we mostly observe
      decomposition of the anion. On the stoichiometric CeO2(111) surface, however, a
      layer of surface-anchored organic products with high thermal stability is formed
      upon reaction of the cation. The suggested acid-base reaction pathway may provide
      well-defined functionalized IL/solid interfaces on basic oxides. 

PMID- 26291208
TI  - Monte Carlo Simulations of Charge Transport in 2D Organic Photovoltaics.
AB  - The effect of morphology on charge transport in organic photovoltaics is assessed
      using Monte Carlo. In isotopic two-phase morphologies, increasing the domain size
      from 6.3 to 18.3 nm improves the fill factor by 11.6%, a result of decreased
      tortuosity and relaxation of Coulombic barriers. Additionally, when small
      aggregates of electron acceptors are interdispersed into the electron donor
      phase, charged defects form in the system, reducing fill factors by 23.3% on
      average, compared with systems without aggregates. In contrast, systems with
      idealized connectivity show a 3.31% decrease in fill factor when domain size was
      increased from 4 to 64 nm. We attribute this to a decreased rate of exciton
      separation at donor-acceptor interfaces. Finally, we notice that the presence of
      Coulomb interactions increases device performance as devices become smaller. The
      results suggest that for commonly found isotropic morphologies the Coulomb
      interactions between charge carriers dominates exciton separation effects. 

PMID- 26291209
TI  - Tailored Parallel Graphene Stripes in Plastic Film with Conductive Anisotropy by
      Shear-Induced Self-Assembly.
AB  - We present a simple but efficient route to prepare a highly anisotropic
      conductive plastic thin film from the polypropylene/(styrene-ethylene/butadiene
      styrene) triblock copolymer/graphene blend via shear-induced self-assembly. Under
      the shear-flow induction, GE nanosheets dispersed in the polymer matrix can
      spontaneously assemble into ordered parallel stripes, which endow the materials
      significantly conductive anisotropy. The electrical resistivity in the direction
      parallel to the graphene stripes is almost four orders of magnitude lower than
      that which is perpendicular to the stripes. This study provides a new method for
      the precise control of the organization of functional nano-objects in polymer
      matrix, which can be widely extended to the fabrication of other multifunctional
      anisotropic materials of interest in various fields. 

PMID- 26291210
TI  - Ring Polymer Molecular Dynamics Calculations of Thermal Rate Constants for the
      O((3)P) + CH4 -> OH + CH3 Reaction: Contributions of Quantum Effects.
AB  - The thermal rate constant of the O((3)P) + CH4 -> OH + CH3 reaction is
      investigated with ring polymer molecular dynamics on a full-dimensional potential
      energy surface. Good agreement with experimental and full-dimensional quantum
      multiconfiguration time-dependent Hartree results between 300 and 1500 K was
      obtained. It is shown that quantum effects, for example, tunneling and zero-point
      energy, can be effectively and efficiently included in this path-integral based
      approach implemented with classical trajectories. Convergence with respect to the
      number of beads is rapid, suggesting wide applicability for other reactions
      involving polyatomic molecules. 

PMID- 26291211
TI  - Water Chain Formation on TiO2(110).
AB  - The adsorption of water on a reduced rutile TiO2(110)-(1*1) surface has been
      investigated using scanning tunneling microscopy (STM) and density functional
      theory (DFT) calculations. The STM measurements show that at a temperature of 50
      K, an isolated water monomer adsorbs on top of a Ti(5f) atom on the Ti row in
      agreement with earlier studies. As the coverage increases, water molecules start
      to form one-dimensional chain structures along the Ti row direction. Supporting
      DFT calculations show that the formation of an H-bonded one-dimensional water
      chain is energetically favorable compared to monomer adsorption. In the chain,
      there are H-bonds between adjacent water molecules, and the water molecules also
      form H-bonds to neighboring bridging oxygens of TiO2(110). Thermal annealing at T
      = 190 K leads to the formation of longer chains facilitated by the diffusion of
      water on the surface. The results provide insight into the nature of the hydrogen
      bonding in the initial stage of wetting of TiO2. 

PMID- 26291212
TI  - Formation of Carbon-Carbon Triply Bonded Molecules from Two Free Carbyne Radicals
      via a Conical Intersection.
AB  - The recent proposal (Bogoslavsky, B.; Levy, O.; Kotlyar, A.; Salem, M.; Gelman,
      F.; Bino, A. Angew. Chem., Int. Ed.2012, 51, 90-94) that metallo-alkylidyne
      complexes decompose in aqueous solution and give rise to free carbynes, which
      couple to yield acetylenes, is examined here theoretically. On the basis of the
      known marker reactions of carbynes in the doublet and quartet state, it is
      concluded that most of the reactivity patterns observed in the Bino experiment
      arose from quartet carbynes. Indeed, theory shows that quartet carbynes can be
      funneled to acetylene via a conical intersection. Moreover, many of the minor
      products are also identified as markers of the quartet carbynes. Carbynes
      formation in their doublet state is a minor channel that branches from the
      conical intersection and leads to the formation of dienes and olefins in the Bino
      experiment. Thus, we show that conical intersections are important also in
      thermally initiated reactions. Coupled to the experimental approach, the study
      opens a window to studies of carbynes under mild conditions. 

PMID- 26291213
TI  - Disentangling the Puzzle of Hydrogen Bonding in Vitamin C.
AB  - Fast-passage Fourier transform microwave spectroscopy in combination with a laser
      ablation source has been successfully applied to probe vitamin C (l-ascorbic
      acid) in the gas phase. Its ethyldiol side chain and two hydroxyl groups around
      the gamma-lactone ring provide five internal rotation axes, enabling vitamin C to
      assume a wide variety of nonplanar 3D cooperative hydrogen bond networks that can
      also include the keto and ether functions. The rotational constants extracted
      from the analysis of the spectrum unequivocally identify the existence of three
      dominant conformers stabilized by different intramolecular hydrogen bonding
      motifs forming five-, six-, or seven-membered rings. 

PMID- 26291214
TI  - Amyloid Fibril-Induced Structural and Spectral Modifications in the Thioflavin-T
      Optical Probe.
AB  - Motivated by future possibilities to design target molecules for fibrils with
      diagnostic or therapeutic capability related to amyloidosis diseases, we
      investigate in this work the dielectric nature of amyloid fibril
      microenvironments in different binding sites using an optical probe, thioflavin-T
      (THT), which has been used extensively to stain such fibrils. We study the fibril
      environment-induced structural and spectral changes of THT at each binding site
      and compare the results to the fibril-free situation in aqueous solution. All
      binding sites are found to show a similar effect with respect to the
      conformational changes of THT; in the presence of the fibril, its molecular
      geometry tends to become planarized. However, depending on the dielectric nature
      of the specific binding site, a red shift, blue shift, or no shift in the
      absorption spectra of THT is predicted. Interestingly, the experimentally
      measured red shift in the spectra is seen only when THT binds to one of the core
      or surface-binding sites. It is found that the dielectric nature of the
      microenvironment in the fibril is strongly nonhomogeneous. 

PMID- 26291215
TI  - Polypeptide Translocation Through the Mitochondrial TOM Channel: Temperature
      Dependent Rates at the Single-Molecule Level.
AB  - The TOM protein complex facilitates the transfer of nearly all mitochondrial
      preproteins across outer mitochondrial membranes. Here we characterized the
      effect of temperature on facilitated translocation of a mitochondrial presequence
      peptide pF1beta. Ion current fluctuations analysis through single TOM channels
      revealed thermodynamic and kinetic parameters of substrate binding and allowed
      determining the energy profile of peptide translocation. The activation energy
      for the on-rate and off-rate of the presequence peptide into the TOM complex was
      symmetric with respect to the electric field and estimated to be about 15 and 22
      kT per peptide. These values are above that expected for free diffusion of ions
      in water (6 kT) and reflect the stronger interaction in the channel. Both values
      are in the range for typical enzyme kinetics and suggest one process without
      involving large conformational changes within the channel protein. 

PMID- 26291216
TI  - Vibrational Sum Frequency Generation Spectroscopy of the Water Liquid-Vapor
      Interface from Density Functional Theory-Based Molecular Dynamics Simulations.
AB  - The vibrational sum frequency generation (VSFG) spectrum of the water liquid
      vapor (LV) interface is calculated using density functional theory-based
      molecular dynamics simulations. The real and imaginary parts of the spectrum are
      in good agreement with the experimental data, and we provide an assignment of the
      SFG bands according to the dipole orientation of the interfacial water molecules.
      We use an instantaneous definition of the surface, which is more adapted to the
      study of interfacial phenomena than the Gibbs dividing surface. By calculating
      the vibrational (infrared, Raman) properties for interfaces of varying thickness,
      we show that the bulk spectra signatures appear after a thin layer of 2-3 A only.
      We therefore use this value as a criterion for calculating the VSFG spectrum. 

PMID- 26291217
TI  - Raman Staircase in Charge Transfer SERS at the Junction of Fusing Nanospheres.
AB  - We present a theoretical analysis of Raman intensities for a molecule that
      bridges a current carrying junction. Experimental data is used to estimate
      parameters for the theoretical model. The recently reported staircase of Raman
      intensities observed during the fusion of nanodumbbell is reproduced. 

PMID- 26291218
TI  - Probing the Reaction Kinetics of the Charge Reactions of Nonaqueous Li-O2
      Batteries.
AB  - Understanding the reaction mechanism of nonaqueous oxygen reduction reaction
      (ORR) and oxygen evolution reaction (OER) is key to increase the low round-trip
      efficiency and power capability of rechargeable Li-air batteries. Here we show
      that the ORR kinetics are much faster than OER kinetics and OER occurs in two
      distinct stages upon Li-air battery charging. The first OER stage occurs at low
      overpotentials (<400 mV) with a slopping voltage profile, whose kinetics are
      relatively insensitive to charge rates and catalysts. This OER stage could be
      attributed to the delithiation of the outer part of Li2O2 forming lithium
      deficient Li2-xO2, which is chemically disproportionate to evolve O2. The second
      stage takes place at high overpotentials (400-1200 mV), whose kinetics are
      sensitive to discharge/charge rates and catalysts, which can be attributed to the
      oxidation of bulk Li2O2 particles. Our study provides insights into bridging
      current two schools of thought on the OER mechanism. 

PMID- 26291219
TI  - Atomic-Scale Mechanism of Efficient Hydrogen Evolution at SiC Nanocrystal
      Electrodes.
AB  - Efficient electrochemical hydrogen evolution at ultrathin 3C-SiC nanocrystal
      electrodes in acid solutions was recently reported, but the atomic-scale
      mechanism of the reaction was not identified. Here we report quantum mechanical
      calculations of pertinent reactions and show that the reaction happens at pre
      existing hydrogenated surface Si-H sites through a mechanism that is related to
      the Volmer-Heyrovsky mechanism that occurs in metals. Here the Heyrovsky reaction
      occurs as the first step, where an electron from the substrate reacts with a
      hydronium adsorbed at a Si-H site, creating an H2 molecule and a Si dangling
      bond. The Volmer reaction follows and regenerates the Si-H. This ordering of
      reactions is supported by the fact that the hydrogen coverage on SiC electrodes
      does not depend on the applied voltage, in contrast to the cases of metal
      electrodes. Moreover, the Volmer reaction, which is a one-step process on metal
      surface, is a two-step process here. We then show that the rise of the conduction
      band due to quantum confinement accounts for the fact that only ultrasmall SiC
      nanocrystals are electrochemically active. We also show that the ability of a Si
      H bond to bind a hydronium is essential for the hydrogen evolution to occur at
      high rate. 

PMID- 26291220
TI  - Anions, the Reporters of Structure in Ionic Liquids.
AB  - In this work we compare the role that different anions play in the structure
      function S(q) for a set of liquids with the same cation. It is well established
      that because of their amphiphilic nature and their often larger size, cations
      play a fundamental role in the structural landscape of ionic liquids. On the
      other hand, it is often atoms in the anions that display the largest X-ray form
      factors and therefore play a very significant role as reporters of structure in
      small- and wide-angle X-ray scattering (SAXS/WAXS)-type experiments. For a set of
      liquids with similar topological landscape, how does S(q) change when the anionic
      scattering is deemphasized? Also, how do we computationally recover the typical
      length scale of important and perhaps universal ionic liquid structural features
      such as charge alternation when these are experimentally inaccessible from S(q)
      because of interference cancellations? We answer these questions by studying
      three different tetrapentylammonium-based liquids with the I(-), PF6(-) and
      N(CN)2(-) anions. 

PMID- 26291221
TI  - Boosting Dissolution Dynamic Nuclear Polarization by Cross Polarization.
AB  - The efficiency of dissolution dynamic nuclear polarization can be boosted by
      Hartmann-Hahn cross polarization at temperatures near 1.2 K. This enables high
      throughput of hyperpolarized solutions with substantial gains in buildup times
      and polarization levels. During dissolution and transport, the (13)C nuclear spin
      polarization P((13)C) merely decreases from 45 to 40%. 

PMID- 26291222
TI  - Robust Superlubricity in Graphene/h-BN Heterojunctions.
AB  - The sliding energy landscape of the heterogeneous graphene/h-BN interface is
      studied by means of the registry index. For a graphene flake sliding on top of h
      BN, the anisotropy of the sliding energy corrugation with respect to the misfit
      angle between the two naturally mismatched lattices is found to reduce with the
      flake size. For sufficiently large flakes, the sliding energy corrugation is
      expected to be at least an order of magnitude lower than that obtained for
      matching lattices regardless of the relative interlayer orientation. Therefore,
      in contrast to the case of the homogeneous graphene interface where flake
      reorientations are known to eliminate superlubricty, here, a stable low-friction
      state is expected to occur. Our results mark heterogeneous layered interfaces as
      promising candidates for dry lubrication purposes. 

PMID- 26291223
TI  - A Pathway to Type-I Band Alignment in Ge/Si Core-Shell Nanowires.
AB  - We investigate the electronic band structures of Ge/Si core-shell nanowires
      (CSNWs) and devise a way to realize the electron quantum well at Ge core atoms
      with first-principles calculations. We reveal that the electronic band
      engineering by the quantum confinement and the lattice strain can induce the type
      I/II band alignment transition, and the resulting type-I band alignment generates
      the electron quantum well in Ge/Si CSNWs. We also find that the type-I/II
      transition in Ge/Si CSNWs is highly related to the direct to indirect band gap
      transition through the analysis of charge density and band structures. In terms
      of the quantum confinement, for [100] and [111] directional Ge/Si CSNWs, the type
      I/II transition can be obtained by decreasing the diameters, whereas a [110]
      directional CSNW preserves the type-II band alignment even at diameters as small
      as 1 nm. By applying a compressive strain on [110] CSNWs, the type-I band
      alignment can be formed. Our results suggest that Ge/Si CSNWs can have the type-I
      band alignment characteristics by the band structure engineering, which enables
      both n-type and p-type quantum-well transistors to be fabricated using Ge/Si
      CSNWs for high-speed logic applications. 

PMID- 26291224
TI  - On the Challenge of Electrolyte Solutions for Li-Air Batteries: Monitoring Oxygen
      Reduction and Related Reactions in Polyether Solutions by Spectroscopy and EQCM.
AB  - Polyether solvents are considered interesting and important candidates for Li-O2
      battery systems. Discharge of Li-O2 battery systems forms Li oxides. Their
      mechanism of formation is complex. The stability of most relevant polar aprotic
      solvents toward these Li oxides is questionable. Specially high surface area
      carbon electrodes were developed for the present work. In this study, several
      spectroscopic tools and in situ measurements using electrochemical quartz crystal
      microbalance (EQCM) were employed to explore the discharge-charge processes and
      related side reactions in Li-O2 battery systems containing electrolyte solutions
      based on triglyme/lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) electrolyte
      solutions. The systematic mechanism of lithium oxides formation was monitored. A
      combination of Fourier transform infrared (FTIR), NMR, and matrix-assisted laser
      desorption/ionization (MALDI) measurements in conjunction with electrochemical
      studies demonstrated the intrinsic instability and incompatibility of polyether
      solvents for Li-air batteries. 

PMID- 26291225
TI  - On the Atomistic Nature of Capacitance Enhancement Generated by Ionic Liquid
      Electrolyte Confined in Subnanometer Pores.
AB  - The capacitance enhancement experimentally observed in electrodes with complex
      morphology of random subnanometer wide pores is an intriguing phenomena, yet the
      mechanisms for such enhancement are not completely understood. Our atomistic
      molecular dynamics simulations demonstrate that in subnanometer slit-geometry
      nanopores, a factor of 2 capacitance enhancement (compared to a flat electrode)
      is possible for the 1-ethyl-3-methylimidazolium (EMIM)-bis(trifluoro
      methylsulfonyl)imide (TFSI) ionic liquid electrolyte. This capacitance
      enhancement is a result of a fast charge separation inside the nanopore due to
      abrupt expulsion of co-ions from the pore while maintaining an elevated
      counterion density due to strong screening of electrostatic repulsive
      interactions by the conductive pore. Importantly, we find that the capacitance
      enhancement can be very asymmetric. For the negatively charged 7.5 A wide pore,
      the integral capacitance is 100% larger than on a flat surface; however, on the
      positive electrode, almost no enhancement is observed. Detailed analysis of
      structure and composition of electrolyte inside nanopores shows that the
      capacitance enhancement and the shape of differential capacitance strongly depend
      on the details of the ion chemical structure and a delicate balance of ion
      surface and ion-ion interactions. 

PMID- 26291226
TI  - Harnessing Infrared Photons for Photoelectrochemical Hydrogen Generation. A PbS
      Quantum Dot Based "Quasi-Artificial Leaf".
AB  - Hydrogen generation by using quantum dot (QD) based heterostructures has emerged
      as a promising strategy to develop artificial photosynthesis devices. In the
      present study, we sensitize mesoporous TiO2 electrodes with in-situ-deposited
      PbS/CdS QDs, aiming at harvesting light in both the visible and the near-infrared
      for hydrogen generation. This heterostructure exhibits a remarkable photocurrent
      of 6 mA.cm(-2), leading to 60 mL.cm(-2).day(-1) hydrogen generation. Most
      importantly, confirmation of the contribution of infrared photons to H2
      generation was provided by the incident-photon-to-current-efficiency (IPCE), and
      the integrated current was in excellent agreement with that obtained through
      cyclic voltammetry. The main electronic processes (accumulation, transport, and
      recombination) were identified by impedance spectroscopy, which appears as a
      simple and reliable methodology to evaluate the limiting factors of these
      photoelectrodes. On the basis of this TiO2/PbS/CdS heterostructrure, a "quasi
      artificial leaf" has been developed, which has proven to produce hydrogen under
      simulated solar illumination at (4.30 +/- 0.25) mL.cm(-2).day(-1). 

PMID- 26291227
TI  - Understanding Interfaces in Metal-Graphitic Hybrid Nanostructures.
AB  - Metal-graphitic interfaces formed between metal nanoparticles (MNPs) and carbon
      nanotubes (CNTs) or graphene play an important role in the properties of such
      hybrid nanostructures. This Perspective summarizes different types of interfaces
      that exist within the metal-carbon nanoassemblies and discusses current efforts
      on understanding and modeling the interfacial conditions and interactions.
      Characterization of the metal-graphitic interfaces is described here, including
      microscopy, spectroscopy, electrochemical techniques, and electrical
      measurements. Recent studies on these nanohybrids have shown that the metal
      graphitic interfaces play critical roles in both controlled assembly of
      nanoparticles and practical applications of nanohybrids in chemical sensors and
      fuel cells. Better understanding, design, and manipulation of metal-graphitic
      interfaces could therefore become the new frontier in the research of MNP/CNT or
      MNP/graphene hybrid systems. 

PMID- 26291228
TI  - High-Resolution Photocurrent Imaging of Bulk Heterojunction Solar Cells.
AB  - Images obtained from photocurrent scanning of organic bulk heterojunction solar
      cell devices provide a direct measure of correlation of the morphology to the
      performance parameters. The peripheral photocurrent induced from light coupled to
      probe tips in the near-field regime of bulk heterojunction layers permits in situ
      scanning of active solar cells with asymmetric electrodes. We present a
      methodology involving a combination of atomic force microscopy, near-field
      optical microscopy, and near-field photocurrent microscopy to decipher the
      carrier generation and transport regions in the bulk heterojunction layer. The
      angular Fourier transformation technique is implemented on these images to
      rationalize the optimum blend concentration in crystalline and amorphous donor
      systems and provide insights into the role of the bulk heterojunction morphology.

PMID- 26291229
TI  - In Vacuo Photoemission Studies of Platinum Atomic Layer Deposition Using
      Synchrotron Radiation.
AB  - The mechanism of platinum atomic layer deposition using
      (methylcyclopentadienyl)trimethylplatinum and oxygen is investigated with in
      vacuo photoemission spectroscopy at the Stanford Synchrotron Radiation
      Lightsource. With this surface-sensitive technique, the surface species following
      the Pt precursor half cycle and the oxygen counter-reactant half cycle can be
      directly measured. We observed significant amounts of carbonaceous species
      following the Pt precursor pulse, consistent with dehydrogenation of the
      precursor ligands. Significantly more carbon is observed when deposition is
      carried out in the thermal decomposition temperature region. The carbonaceous
      layer is removed during the oxygen counter reactant pulse, and the photoemission
      spectrum shows that a layer of adsorbed oxygen remains on the surface as
      previously predicted. 

PMID- 26291230
TI  - Role of Interparticle Charge Transfers in Agglomerated Photocatalyst
      Nanoparticles: Demonstration in Aqueous Suspension of Dye-Sensitized TiO2.
AB  - The interparticle charge transfer within the agglomerates of TiO2 nanoparticles
      in slurries markedly enhanced the dye-sensitized production of H2 under visible
      light. By purposely decoupling the light absorbing part of Dye/TiO2 from the
      active catalytic center of Pt/TiO2, the role of bare TiO2 nanoparticles working
      as a mediator that connects the above two parts in the agglomerates was
      investigated systematically. The presence of mediator in the agglomerate
      facilitated the charge separation and the electron transfer from Dye/TiO2 to
      Pt/TiO2 through multiple grain boundaries and subsequently produced more
      hydrogen. The dye-sensitized reduction of Cr(VI) to Cr(III) was also enhanced
      when Dye/TiO2 nanoparticles were agglomerated with bare TiO2 nanoparticles. The
      charge recombination between the oxidized dye and the injected electron was
      retarded in the presence of bare TiO2 nanoparticles, and this retarded
      recombination on Dye/TiO2 was confirmed by using transient laser spectroscopy.
      This phenomenon can be rationalized in terms of an interparticle Fermi level
      gradient within the agglomerates, which drives the charge separation. 

PMID- 26291231
TI  - Photomediated Oxidation of Atomically Precise Au25(SC2H4Ph)18(-) Nanoclusters.
AB  - The anionic charge of atomically precise Au25(SC2H4Ph)18(-) nanoclusters
      (abbreviated as Au25(-)) is thought to facilitate the adsorption and activation
      of molecular species. We used optical spectroscopy, nonaqueous electrochemistry,
      and density functional theory to study the interaction between Au25(-) and O2.
      Surprisingly, the oxidation of Au25(-) by O2 was not a spontaneous process.
      Rather, Au25(-)-O2 charge transfer was found to be a photomediated process
      dependent on the relative energies of the Au25(-) LUMO and the O2 electron
      accepting level. Photomediated charge transfer was not restricted to one
      particular electron accepting molecule or solvent system, and this phenomenon
      likely extends to other Au25(-)-adsorbate systems with appropriate electron donor
      acceptor energy levels. These findings underscore the significant and sometimes
      overlooked way that photophysical processes can influence the chemistry of ligand
      protected clusters. In a broader sense, the identification of photochemical
      pathways may help develop new cluster-adsorbate models and expand the range of
      catalytic reactions available to these materials. 

PMID- 26291232
TI  - Controlling Orientational Order in 1-D Assemblies of Multivalent Triangular
      Prisms.
AB  - Multivalent nanostructures are becoming an increasingly important player in the
      self-assembly of supramolecular lattices. Understanding the role that shape plays
      in the coordination of the assemblies is crucial for the functional response of
      the material. We develop a simple design rule for the assembly of multivalent Au
      triangular nanoprisms into 1-D ordered arrays based on both the length of the
      valent DNA and the aspect ratio of the prism. Using MD simulations, we describe
      an order parameter that captures the short-range order of the assembly controlled
      by the design parameters. The order parameter shows that even short chains (N =
      4) of prisms have a high degree of orientational order that transitions to no
      orientational order when the DNA length is similar to the prism length. Unlike
      isotropic polyvalent assemblies, we find that the highly oriented chains of
      prisms lose orientational order in discrete steps during melting as the prisms in
      the arrays dissociate. 

PMID- 26291234
TI  - CO Oxidation at the Interface of Au Nanoclusters and the Stepped-CeO2(111)
      Surface by the Mars-van Krevelen Mechanism.
AB  - DFT+U calculations of CO oxidation by Au12 nanoclusters supported on a stepped
      CeO2(111) surface show that lattice oxygen at the step edge oxidizes CO bound to
      Au NCs by the Mars-van Krevelen (M-vK) mechanism. We found that CO2 desorption
      determines the rate of CO oxidation, and the vacancy formation energy is a
      reactivity descriptor for CO oxidation. Our results suggest that the M-vK
      mechanism contributes significantly to CO oxidation activity at Au particles
      supported on the nano- or meso-structured CeO2 found in industrial catalysts. 

PMID- 26291233
TI  - Charge-Transfer State Dynamics Following Hole and Electron Transfer in Organic
      Photovoltaic Devices.
AB  - The formation of bound electron-hole pairs, also called charge-transfer (CT)
      states, in organic-based photovoltaic devices is one of the dominant loss
      mechanisms hindering performance. Whereas CT state dynamics following electron
      transfer from donor to acceptor have been widely studied, there is not much known
      about the dynamics of bound CT states produced by hole transfer from the acceptor
      to the donor. In this letter, we compare the dynamics of CT states formed in the
      different charge-transfer pathways in a range of model systems. We show that the
      nature and dynamics of the generated CT states are similar in the case of
      electron and hole transfer. However the yield of bound and free charges is
      observed to be strongly dependent on the HOMOD-HOMOA and LUMOD-LUMOA energy
      differences of the material system. We propose a qualitative model in which the
      effects of static disorder and sampling of states during the relaxation determine
      the probability of accessing CT states favorable for charge separation. 

PMID- 26291235
TI  - Investigation of Catalytic Finite-Size-Effects of Platinum Metal Clusters.
AB  - In this paper, we use density functional theory (DFT) calculations on highly
      parallel computing resources to study size-dependent changes in the chemical and
      electronic properties of platinum (Pt) for a number of fixed freestanding
      clusters ranging from 13 to 1415 atoms, or 0.7-3.5 nm in diameter. We find that
      the surface catalytic properties of the clusters converge to the single crystal
      limit for clusters with as few as 147 atoms (1.6 nm). Recently published results
      for gold (Au) clusters showed analogous convergence with size. However, this
      convergence happened at larger sizes, because the Au d-states do not contribute
      to the density of states around the Fermi-level, and the observed level
      fluctuations were not significantly damped until the cluster reached ca. 560
      atoms (2.7 nm) in size. 

PMID- 26291236
TI  - Emerging Research Frontiers in Physical Chemistry.

PMID- 26291237
TI  - Metal-Organic Framework (MOF) Defects under Control: Insights into the Missing
      Linker Sites and Their Implication in the Reactivity of Zirconium-Based
      Frameworks.
AB  - For three-dimensional (3D) metal-organic frameworks (MOFs), the presence and
      nature of structural defects has been recognized as a key factor shaping the
      material's physical and chemical behavior. In this work, the formation of the
      "missing linker" defects has been addressed in the model biphenyl-4,4'
      dicarboxylate (bpdc)-based Zr MOF, UiO-67. The defect showed strong dependence on
      the nature of the modulator acid used in the MOF synthesis; the defects, in turn,
      were found to correlate with the MOF physical and chemical properties. The
      dynamic nature of the Zr6 (node)-monocarboxylate bond showed promise in defect
      functionalization and "healing", including the formation of X-ray-quality "defect
      free" UiO-67 single crystals. Chemical transformations at defect sites have also
      been explored. The study was also extended to the isoreticular UiO-66 and UiO-68'
      systems. 

PMID- 26291238
TI  - Use of Pneumococcal Disease Epidemiology to Set Policy and Prevent Disease during
      20 Years of the Emerging Infections Program.
AB  - Two decades ago, the Emerging Infections Program of the US Centers for Disease
      Control and Prevention implemented what seemed like a simple yet novel idea: a
      population- and laboratory-based surveillance system designed to identify and
      characterize invasive bacterial infections, including those caused by
      Streptococcus pneumoniae. This system, known as Active Bacterial Core
      surveillance, has since served as a flexible platform for following trends in
      invasive pneumococcal disease and studying vaccination as the most effective
      method for prevention. We report the contributions of Active Bacterial Core
      surveillance to every pneumococcal vaccine policy decision in the United States
      during the past 20 years. 

PMID- 26291239
TI  - Synthetic Polymers from Sugar-Based Monomers.

PMID- 26291240
TI  - Lanthanum(III) and Lutetium(III) in Nitrate-Based Ionic Liquids: A Theoretical
      Study of Their Coordination Shell.
AB  - By using ab initio molecular dynamics, we investigate the solvent shell structure
      of La(3+) and Lu(3+) ions immersed in two ionic liquids, ethylammonium nitrate
      (EAN) and its hydroxy derivative (2-ethanolammonium nitrate, HOEAN). We provide
      the first study of the coordination properties of these heavy metal ions in such
      a highly charged nonacqueous environment. We find, as expected, that the
      coordination in the liquid is mainly due to nitrate anions and that, due to the
      bidentate nature of the ligand, the complexation shell of the central ion has a
      nontrivial geometry and a coordination number in terms of nitrate molecules that
      apparently violates the decrease of ionic radii along the lanthanides series,
      since the smaller Lu(3+) ion seems to coordinate six nitrate molecules and the
      La(3+) ion only five. A closer inspection of the structural features obtained
      from our calculations shows, instead, that the first shell of oxygen atoms is
      more compact for Lu(3+) than for La(3+) and that the former coordinates 8 oxygen
      atoms while the latter 10 in accord with the typical lanthanide's trend along the
      series and that their first solvation shells have a slight irregular and complex
      geometrical pattern. When moving to the HOEAN solutions, we have found that the
      solvation of the central ion is possibly also due to the cation itself through
      the oxygen atom on the side chain. Also, in this liquid, the coordination numbers
      in terms of oxygen atoms in both solvents is 10 for La(3+) and 8 for Lu(3+). 

PMID- 26291241
TI  - 21(st) Century Cures Act: An Act of Cure or Diagnosis?

PMID- 26291242
TI  - Interview with Alex Zhavoronkov, PhD.

PMID- 26291245
TI  - Physiological functions of the small GTPase Arf6 in the nervous system.
AB  - The small GTPase ADP-ribosylation factor 6 (Arf6) plays important roles in
      membrane dynamics-based neuronal cell events such as neurite outgrowth and spine
      formation. However, physiological functions of Arf6 in the nervous system at
      whole animal level have not yet been explored. We have recently generated
      conditional knockout mice lacking Arf6 in neurons or oligodendrocytes of central
      nervous system (CNS) or both cell lineages, and analyzed them. We found that
      ablation of Arf6 gene from neurons, but not from oligodendrocytes, caused the
      defect in axon myelination at the fimbria of hippocampus (Fim) and corpus
      callosum (CC). We also found that migration of oligodendrocyte precursor cells
      (OPCs) from the subventricular zone to the Fim and CC in mice lacking Arf6 in
      neurons was impaired. Finally, it was found that secretion of fibroblast growth
      factor-2 (FGF-2), a guidance factor for OPC migration, from hippocampi lacking
      Arf6 was impaired. Collectively, these findings demonstrate that Arf6 in neurons
      of the CNS plays an important role in OPC migration by regulating secretion of
      FGF-2 from neurons, thereby contributing to the axon myelination. Here, we
      discuss our current understanding of physiological functions of Arf6 in the
      nervous system. 

PMID- 26291247
TI  - Eat or be eaten: The autophagic plight of inactive 26S proteasomes.
AB  - Two principal pathways in eukaryotes, namely the ubiquitin-proteasome system
      (UPS) and autophagy, mediate selective protein degradation. The UPS typically
      removes short-lived individual misfolded or regulatory polypeptides that have
      been tagged with polyubiquitin chains, whereas autophagy eliminates bulkier
      structures such as large protein complexes, insoluble protein aggregates,
      organelles, and invading intracellular pathogens. Protein degradation within the
      UPS is executed by the 26S proteasome, a large multisubunit proteolytic machine
      whose levels are tightly regulated transcriptionally and during assembly. Our
      recent studies identified a new mechanism for controlling 26S proteasome
      abundance through selective autophagy, which we term proteaphagy. This process is
      separately stimulated by nutrient starvation and proteasome inactivation, the
      latter occurring independently of ATG1 kinase regulation. Removal of inactive
      complexes is instead mediated by the proteasomal ubiquitin receptor RPN10, which
      can simultaneously bind both ubiquitinated proteasomes and lipidated ATG8 lining
      autophagic membranes. 

PMID- 26291246
TI  - Interplay between promoter methylation and chromosomal loss in gene silencing at
      3p11-p14 in cervical cancer.
AB  - Loss of 3p11-p14 is a frequent event in epithelial cancer and a candidate
      prognostic biomarker in cervical cancer. In addition to loss, promoter
      methylation can participate in gene silencing and promote tumor aggressiveness.
      We have performed a complete mapping of promoter methylation at 3p11-p14 in two
      independent cohorts of cervical cancer patients (n = 149, n = 121), using
      Illumina 450K methylation arrays. The aim was to investigate whether hyperm
      ethylation was frequent and could contribute to gene silencing and disease
      aggressiveness either alone or combined with loss. By comparing the methylation
      level of individual CpG sites with corresponding data of normal cervical tissue,
      26 out of 41 genes were found to be hypermethylated in both cohorts. The
      frequency of patients with hypermethylation of these genes was found to be higher
      at tumor stages of 3 and 4 than in stage 1 tumors. Seventeen of the 26 genes were
      transcriptionally downregulated in cancer compared to normal tissue, whereof 6
      genes showed a significant correlation between methylation and expression.
      Integrated analysis of methylation, gene dosage, and expression of the 26
      hypermethylated genes identified 3 regulation patterns encompassing 8
      hypermethylated genes; a methylation driven pattern (C3orf14, GPR27, ZNF717), a
      gene dosage driven pattern (THOC7, PSMD6), and a combined methylation and gene
      dosage driven pattern (FHIT, ADAMTS9, LRIG1). In survival analysis, patients with
      both hypermethylation and loss of LRIG1 had a worse outcome compared to those
      harboring only hypermethylation or none of the events. C3orf14 emerged as a novel
      methylation regulated suppressor gene, for which knockdown was found to promote
      invasive growth in human papilloma virus (HPV)-transformed keratinocytes. In
      conclusion, hypermethylation at 3p11-p14 is common in cervical cancer and may
      exert a selection pressure during carcinogenesis alone or combined with loss.
      Information on both events could lead to improved prognostic markers. 

PMID- 26291248
TI  - The legacy of gender-based violence and HIV/AIDS in the postgenocide era: Stories
      from women in Rwanda.
AB  - Drawing on qualitative interviews with 22 Rwandan women, we describe the lived
      experiences of women survivors of gender-based violence (GBV) more than a decade
      and a half after the 1994 Genocide. We argue that the intersection between GBV
      and human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS)
      has long-term implications: the majority of women interviewed continue to endure
      trauma, stigma, social isolation, and economic hardship in the postgenocide era
      and are in need of expanded economic and mental health support. Our findings have
      implications for the importance of providing integrated psychosocial support to
      survivors of GBV postconflict contexts.

PMID- 26291249
TI  - Umbilical Cord Coiling and Zygosity: Is there a Link?
AB  - INTRODUCTION: The aim of this study was to analyze abnormalities of umbilical
      coiling index (UCI) in twin gestation to test whether the coiling is genetically
      influenced by zygosity. METHODS: Data retrieved comprised gestational age (GA),
      chorionicity, fetal gender, and UCI. RESULTS: The mean UCI of hypercoiled cords
      in monochorionic placentas was 0.55 coils/cm and 0.49 coils/cm in dichorionic
      placentas with discordant fetal gender (P = 0.2629). DISCUSSION: In conclusion,
      no significant statistical difference between UCI in monochorionic and
      dichorionic twin placentas with discordant fetal gender was identified,
      suggesting that zygosity does not play a role in umbilical coiling induction.

PMID- 26291250
TI  - RIFM fragrance ingredient safety assessment, Isoborneol, CAS Registry Number 124
      76-5.
AB  - The use of this material under current use conditions is supported by the
      existing information. This material was evaluated for genotoxicity, repeated dose
      toxicity, developmental toxicity, reproductive toxicity, local respiratory
      toxicity, phototoxicity, skin sensitization potential as well as environmental
      safety. Repeated dose toxicity was determined to have the most conservative
      systemic exposure derived NOAEL of 15 mg/kg/day based on a gavage 13-week
      subchronic toxicity study conducted in rats on a read across analog resulting in
      a MOE of 1000 considering 100% absorption from skin contact and inhalation. A MOE
      of >100 is deemed acceptable. 

PMID- 26291251
TI  - What is the major public health problem: the morbid obesity or the bariatric
      surgery in the unified health system? (Part II).

PMID- 26291252
TI  - Accuracy of doppler ultrasonography in the evaluation of hemodialysis
      arteriovenous fistula maturity.
AB  - OBJECTIVE: to determine the accuracy of Doppler ultrasonography (USD) for
      hemodialysis arteriovenous fistula (AVF) maturity. METHODS: we included patients
      with no prior AVF. Each patient underwent two USD examinations. After initiation
      of hemodialysis, we followed the patients during the first month of the access
      use and verified its adequacy to hemodialysis sessions. At statistical analysis
      we measured specificity, sensitivity, accuracy, ROC curve (Receiver operator
      characteristic) curve, TG-ROC (Two graph - receiver operator characteristic) and
      logistic regression. RESULTS: we included 76 patients, of which 51 completed the
      study. They formed two groups, those who have had good adequacy for hemodialysis
      (45) and those who had not (6). The average flow volume (FV) and the average
      draining vein diameter (DVD) of each group were, respectively: 940mL/min (95% CI:
      829-1052) and 325mL/min (95% CI: 140-510); and 0.48cm (95% CI: 0.45-0.52) and
      0.33cm (95% CI: 0.27-0.40). The area under the ROC curve of FV and DVD were 0.926
      and 0.766, respectively. CONCLUSION: the accuracy of the measured volume flow
      measured at the draining vein to evaluate maturation of hemodialysis
      arteriovenous fistula was 85%.

PMID- 26291253
TI  - Degloving injuries of trunk and limbs: comparison of outcomes of early versus
      delayed assessment by the plastic surgery team.
AB  - OBJECTIVE: to analyze cases of degloving of the trunk and limbs, comparing
      outcomes of early versus delayed assessment by the plastic surgery team. METHODS:
      we conducted a retrospective analysis of medical charts. Patients comprised two
      groups: Group I - early assessment, performed within 12 hours post trauma; and
      Group II - delayed assessment, performed more than 12 hours post trauma. We
      defined primary grafting as the use of skin from the traumatized skin flap. We
      excluded cases involving hands, feet or genitalia. RESULTS: there were 47
      patients treated with degloving injuries between 2002 and 2010. The mean body
      surface area affected was 8.2%. Lower limbs were the most frequently affected
      site (95.7%), whether alone or in association with lesions to other sites.
      Delayed assessment by the plastic surgery team occurred in 25 cases. Mean
      hospital stay was 36.1 days for Group I and 57.1 days for Group II (p=0.026).
      Regarding the number of surgical operations (skin grafts), Group I received a
      mean of 1.3, while Group II underwent 1.6 (p=0.034). CONCLUSION: based on length
      of hospital stay and number of operations in trauma patients with degloving of
      the trunk and limbs, plastic surgery assessment should be carried out early.

PMID- 26291254
TI  - Inguinal hernia repair: can one identify the three main nerves of the region?
AB  - OBJECTIVE: To identify the nerves in the groin during inguinal hernia repair by
      inguinotomy. METHODS: We conducted a prospective, sequenced, non-randomized study
      comprising 38 patients undergoing inguinal hernia repair with placement of
      polypropylene mesh. RESULTS: The male patients were 36 (94.7%), with a mean age
      and standard deviation of 43.1 +/- 14.5, body mass index of 24.4 +/- 2.8.
      Comorbidities were hypertension in two (5.2%), smoking in 12 (31.5%) and obesity
      in two (5.2%). The hernia was located only on the right in 21 (55.2%) patients,
      only on the left in 11 (28.9%), and was bilateral in six (15.7%) patients. Prior
      hernia repair was present in seven (18.4%) patients. The identification of the
      three nerves during operation was made in 20 (52.6%) patients, the ilioinguinal
      nerve and the iliohypogastric nerve were identified in 33 (86.8%), and the
      genital nerve branch of the genitofemoral nerve, in 20 (52.6%). Resection of at
      least one of the nerves was performed in seven (18.4%) cases, two iliohypogastric
      nerves and five ilioinguinal nerves. The average operating time was 70.8 +/- 18.2
      minutes. The hospital stay was 1.42 +/- 1.18 days. Ten patients (26.3%) returned
      to physical activity around the first postoperative visit, and 37 (97.3%) in the
      last. The follow-up time was 95.6 +/- 23.5 days. The inability to identify the
      ilioinguinal nerve was associated with previous repair (p = 0.035). CONCLUSION:
      The identification of the three nerves during inguinal hernia surgery has been
      described in more than half of the cases and prior repair interfered with the
      identification of ilioinguinal nerve.

PMID- 26291255
TI  - Predictive factors for short gastric vessels division during laparoscopic total
      fundoplication.
AB  - OBJECTIVE: to determine clinical variables that can predict the need for division
      of the short gastric vessels (SGV), based on the gastric fundus tension,
      assessing postoperative outcomes in patients submitted or not to section of these
      vessels. METHODS: we analyzed data from 399 consecutive patients undergoing
      laparoscopic fundoplication for gastroesophageal reflux disease (GERD). The
      section of the SGV was performed according to the surgeon evaluation, based on
      the fundus tension. Patients were divided into two groups: not requiring SGV
      section (group A) or requiring SGV section (group B). RESULTS: the section was
      not necessary in 364 (91%) patients (Group A) and required in 35 (9%) patients
      (Group B). Group B had proportionally more male patients and higher average
      height. The endoscopic parameters were worse for Group B, with larger hiatal
      hernias, greater hernias proportion with more than four centimeters, more intense
      esophagitis, higher proportion of Barrett's esophagus and long Barrett's
      esophagus. Male gender and grade IV-V esophagitis were considered independent
      predictors in the multivariate analysis. Transient dysphagia and GERD symptoms
      were more common in Group B. CONCLUSION: the division of the short gastric
      vessels is not required routinely, but male gender and grade IV-V esophagitis are
      independent predictors of the need for section of these vessels.

PMID- 26291256
TI  - Endoscopic treatment of the fistulas after laparoscopic sleeve gastrectomy and
      Roux-en-Y gastric bypass.
AB  - OBJECTIVE: to evaluate the use of endoscopic self-expandable metallic prostheses
      in the treatment of fistulas from sleeve gastrectomy and Roux en y gastric
      bypass. METHODS: all patients were treated with fully coated auto-expandable
      metallic prostheses and were submitted to laparoscopic or CT-guided drainage,
      except for those with intracavitary drains. After 6-8 weeks the prosthesis was
      removed and if the fistula was still open a new prostheses were positioned and
      kept for the same period. RESULTS: the endoscopic treatment was successful in 25
      (86.21%) patients. The main complication was the migration of the prosthesis in
      seven patients. Other complications included prosthesis intolerance,
      gastrointestinal bleeding and adhesions. The treatment failed in four patients
      (13.7%) one of which died (3.4%). CONCLUSION: endoscopic treatment with fully
      coated self-expandable prosthesis was effective in treating most patients with
      fistula after sleeve gastrectomy and roux en y gastric bypass.

PMID- 26291257
TI  - Holmium Laser enucleation of the prostate (HoLEP) versus Transurethral Resection
      of the Prostate (TURP).
AB  - OBJECTIVE: to evaluate the effectiveness and applicability of Holmium laser
      enucleation of the prostate (HoLEP) - in the treatment of benign prostatic
      hyperplasia (BPH) - in comparison to transurethral resection of the prostate
      (TURP). METHODS: patients with symptomatic prostatic hyperplasia and candidates
      for surgical treatment were selected. Both procedures were explained and they had
      choosen HoLEP or TURP. At the hospital were collected: age, date of birth,
      international prostate symptom score, urinary peak flow rate, prostate volume,
      post-voiding residual urine, globular volume and serum PSA. At the procedure
      operating time, morcellating time (HoLEP), bladder mucosal injury and
      intercurrences were collected. At the first postoperative day, globular volume
      and sodium. Besides that were observed the catheter indwelling time and hospital
      stay and after 90 days, urinary peak flow rate and international prostate symptom
      score. Statistical analisys have been done partially by Sinpe(r) and also by a
      professional team. RESULTS: twenty patients in HoLEP group and 21 at TURP were
      operated. Baseline urinary peak flow rate was 8 ml/s in both groups and
      preoperative international prostate symptom score was 22 in HoLEP and 20 in TURP,
      very similar. Operative time was 85 minutes in HoLEP and 60 in TURP, p<0.05.
      Hospital stay was 47 hours for HoLEP and 48 hours to TURP, p<0.05. At 90 day the
      urinary peak flow rate was raised to 21.5 ml/s in HoLEP group and to 20 ml/s in
      TURP and the median of international prostate symptom score had been reduced to
      score 3 in both groups. CONCLUSION: HoLEP is a feasible technique and is as
      effective as TURP on symptomatic prostatic hyperplasia surgical treatment.

PMID- 26291258
TI  - Effect of triamcinolone in keloids morphological changes and cell apoptosis.
AB  - OBJECTIVE: to assess the effects of injectable triamcinolone on keloid scars
      length, height and thickness, and on the number of cells undergoing apoptosis.
      METHODS: This study consists in a prospective, controlled, randomized, single
      blinded clinical trial, conducted with fifteen patients with ear keloids divided
      into two groups: group 1 - seven patients undergoing keloid excisions, and group
      2 - eight patients undergoing keloid excisions after three sessions of
      infiltration with one ml of Triamcinolone hexacetonide (20mg/ml) with three week
      intervals between them and between the last session and surgery. The two groups
      were homogeneous regarding age, gender and evolution of the keloid scar. The
      keloid scars of patients in group 2 were measured for the length, height and
      thickness before triamcinolone injection and before surgery. A blinded observer
      performed morphological detailing and quantification of cells in hematoxylin
      eosin-stained surgical specimens. An apoptotic index was created. RESULTS: The
      apoptotic index in group 1 was 56.82, and in group 2, 68.55, showing no
      significant difference as for apoptosis (p=0.0971). The reduction in keloid
      dimensions in Group 2 was 10.12% in length (p=0.6598), 11.94% in height
      (p=0.4981) and 15.62% in thickness (p=0.4027). CONCLUSION: This study concluded
      that the infiltration of triamcinolone in keloid scars did not increase the
      number of apoptosit and did not reduce keloids' size, length, height or
      thickness.

PMID- 26291259
TI  - Effect of cilostazol on neointimal hyperplasia in iliac arteries of pigs after
      transluminal angioplasty.
AB  - OBJECTIVE: to evaluate whether systemic administration of cilostazol reduces
      neointimal hyperplasia in iliac arteries of pigs submitted to balloon catheter
      angioplasty. METHODS: twenty pigs underwent angioplasty with a 6x40 mm balloon
      catheter in the right common iliac artery, guided by Doppler ultrasound. The
      animals were randomized into two groups: group 1 (n=10), which received 50mg
      cilostazol twice a day, and group 2 (n=10), control. After 30 days, the animals
      were killed and the iliac arteries prepared for histological analysis. The
      histological sections were digitized and analyzed by digital morphometry.
      Statistical analysis was performed using the Student t and Mann-Whitney tests.
      RESULTS: when comparing the iliac arteries submitted to angioplasty with those
      not subjected to angioplasty, there was significant neointimal hyperplasia (0.228
      versus 0.119 mm2; p=0.0001). In arteries undergoing angioplasty, there was no
      difference between group 1 (cilostazol) and group 2 (control) as for the lumen
      area (2.277 versus 2.575 mm2; p=0.08), the tunica intima (0.219 versus 0.237 mm2;
      p=0.64), the tunica media (2.262 vs. 2.393 mm2; p=0.53) and the neointimal
      occlusion percentage (8.857 vs. 9.257 %; p=0.82). CONCLUSION: the use of
      cilostazol 50mg administered in two daily doses did not reduce neointimal
      hyperplasia in iliac arteries of pigs submitted to balloon angioplasty catheter.

PMID- 26291260
TI  - Cell therapy in the treatment of bronchiolitis obliterans in a murine model.
AB  - OBJECTIVE: To evaluate the importance of stem cells derived from adipose tissue
      in reducing graft inflammation in a murine model of allogeneic heterotopic
      tracheal transplant. METHODS: We performed a heterotopic tracheal allografting in
      dorsal subcutaneous pouch and systemically injected 5x105 mesenchymal stem cells
      derived from adipose tissue. The animals were divided into two groups according
      to the time of sacrifice: T7 and T21. We also carried out histological analysis
      and digital morphometry. RESULTS: The T7 animals treated with cell therapy had
      median obstructed graft area of 0 versus 0.54 of controls (p = 0.635). The
      treated T21 subjects had median obstructed graft area of 0.25 versus 0 in
      controls (p = 0.041). CONCLUSION: The systemically injected cell therapy in
      experimental murine model of bronchiolitis obliterans did not reduce the severity
      of the allograft inflammation in a statistically significant way in seven days;
      Conversely, in 21 days, it increased the allograft inflammatory process.

PMID- 26291261
TI  - Proximal endovascular blood flow shunt for thoracoabdominal aortic aneurism
      without total aortic clamping.
AB  - The authors present a surgical approach to type III and IV Crawford aneurysms
      that does not need total aortic clamping, which allows the more objective
      prevention of direct ischemic damage, as well as its exclusion by the
      endoprosthesis implantation, shunting the flow to the synthetic graft. 

PMID- 26291262
TI  - A porcine model for teaching surgical cricothyridootomy.
AB  - OBJECTIVE: To evaluate the acceptability of an educational project using A
      porcine model of airway for teaching surgical cricothyroidotomy to medical
      students and medical residents at a university hospital in southern Brazil.
      METHODS: we developed a teaching project using a porcine model for training in
      surgical cricothyroidotomy. Medical students and residents received lectures
      about this surgical technique and then held practical training with the model.
      After the procedure, all participants filled out a form about the importance of
      training in airway handling and the model used. RESULTS: There were 63
      participants. The overall quality of the porcine model was estimated at 8.8,
      while the anatomical correlation between the model and the human anatomy received
      a mean score of 8.5. The model was unanimously approved and considered useful in
      teaching the procedure. CONCLUSION: the training of surgical cricothyroidotomy
      with a porcine model showed good acceptance among medical students and residents
      of this institution.

PMID- 26291263
TI  - The writing of informed consent in accessible language: difficulties.
AB  - In order to assess the adequacy of informed consent terminology of research
      projects developed at the Clementino Fraga Filho University Hospital (Federal
      University of Rio de Janeiro) , we conducted a review study on the terminology
      found in 55 projects (2008-20013) . Such projects belonged to different medical
      specialties and were all registered in the hospital's Ethics in Research
      Committee. Patients had difficulty in understanding the meanings of 76 medical
      terms and expressions; only 12 of them could be replaced. On the other hand, the
      present study reached the conclusion that, in most cases, the writing with
      scientific terms is essential in items such as justification/objectives and
      procedures, being insurmountable obstacles to the participants of this research
      and patients' understanding. 

PMID- 26291265
TI  - Exploring Sex and Laterality Imbalances in Patients Undergoing Laser Retinopexy.
AB  - IMPORTANCE: Studies have consistently reported a small preponderance of
      rhegmatogenous retinal detachments in males and in right eyes, which might
      suggest interesting differences in ocular anatomy relating to sex and laterality.
      However, an important potential confounding factor is that epidemiologic studies
      do not consider retinal tears that do not lead to detachment. This study used the
      electronic patient records from a large eye hospital to explore whether any sex
      and laterality imbalances were present in patients who underwent laser
      retinopexy. OBSERVATIONS: Analysis was conducted from December 1, 2014, to March
      1, 2015. Of 6760 patients who underwent retinopexy between May 21, 1996, and
      October 27, 2014, sex had been recorded for 5854 patients (3346 males and 2508
      females) and laterality recorded for 3780 eyes (1990 treatments in the right eye
      and 1790 in the left eye). The proportion of males was 57.2% (95% CI, 55.9%
      58.4%) and the proportion of right eyes was 52.6% (95% CI, 51.1%-54.2%). For sex
      and laterality, the 95% CIs did not overlap the 50% mark, indicating that the
      imbalance was likely not owing to chance. CONCLUSIONS AND RELEVANCE: Our study
      showed that laser retinopexy was performed more often in males and in right eyes.
      This imbalance is in the same direction as that seen for retinal detachments,
      suggesting that males and right eyes may have an anatomical predisposition toward
      retinal tears and detachment, possibly related to a slightly greater average
      axial length.

PMID- 26291264
TI  - Barriers along the care cascade of HIV-infected men in a large urban center of
      Brazil.
AB  - Global and national HIV/AIDS policies utilize the care cascade to emphasize the
      importance of continued engagement in HIV services from diagnosis to viral
      suppression. Several studies have documented barriers that men experience in
      accessing services at specific stages of care, but few have analyzed how these
      barriers operate along the care cascade. Brazil offers a unique setting for
      analyzing barriers to HIV care because it is a middle-income country with a large
      HIV epidemic and free, universal access to HIV/AIDS services. Semi-structured
      interviews were conducted in 2011 with HIV-infected men (n = 25) receiving care
      at the only HIV/AIDS state reference center in Salvador, Brazil, the third
      largest city in the country. Interviews were transcribed and coded for analysis.
      Researchers identified barriers to services along the care cascade: health
      service-related obstacles (poor-quality care, lengthy wait times, and drug supply
      problems); psychosocial and emotional challenges (fear of disclosure and
      difficulty accepting HIV diagnosis); indirect costs (transportation and
      absenteeism at work or school); low perceived risk of HIV; and toxicity and
      complexity of antiretroviral drug (ARV) regimens. The stages of the care cascade
      interrupted by each barrier were also identified. Most barriers affected
      multiple, and often all, stages of care, while toxicity and complexity of ARV
      regimens was only present at a single care stage. Efforts to eliminate more
      prevalent barriers have the potential to improve care continuity at multiple
      stages. Going forward, assessing the relative impact of barriers along one's
      entire care trajectory can help tailor improvements in service provision,
      facilitate achievement of viral suppression, and improve access to life-saving
      testing, treatment, and care. 

PMID- 26291267
TI  - Metabolite profiles of Populus in response to pathogen stress.
AB  - Populus canker is a widespread disease that seriously affects the growth and
      productivity of trees, and may even cause tree death. To assess the metabolic
      changes in Populus in response to pathogen stress, Populus stems infected or not
      with Dothiorella gregaria were analyzed by GC-MS. A total of 4, 051 features were
      detected and 44 metabolites were identified to be changed significantly in
      Populus upon infection. The identified responsive metabolites include
      saccharides, alcohols, organic acids, and amino acids and some secondary
      metabolites and most of the metabolites were detected at increased levels.
      Responsive metabolites were investigated about their metabolism pathway and the
      corresponding metabolic networks were further constructed. To our knowledge, this
      is the first study to identify the metabolite profiles of Populus in response to
      pathogen stress. The results extend our understanding of the mechanisms involved
      in the defense of Populus against pathogens and provide a basis for further
      research on plant defenses. 

PMID- 26291266
TI  - Developmental and environmental influences on physiology and behavior--2014 Alan
      N. Epstein Research Award.
AB  - Environmental factors acting during development of an individual may influence
      future health and disease susceptibility. Stressors, including altered diet,
      psychosocial stress, and immune challenge, during gestation can have negative
      consequences on the intrauterine environment and increase disease susceptibility
      of the developing fetus. The long-term effects on offspring have been observed in
      humans and include greater susceptibility to psychiatric disease, such as
      depression and anxiety disorders, and adverse metabolic conditions including
      obesity, diabetes and cardiovascular disease. Studies in my laboratory use rodent
      models and incorporate a multilevel approach to determine the behavioral,
      physiological, and neurobiological correlates of disease development as a
      consequence of early life stressors. The road I took in developing this research
      program was a rather circuitous one and navigating that path would not have been
      possible without the many mentors, colleagues, fellows and students who provided
      critical support. Although my name appears on the plaque of the Alan N. Epstein
      Research Award, I share this with all those I had the privilege of working with
      along that road, as briefly summarized in this article. 

PMID- 26291269
TI  - Optimisation of a simple method to transiently transfect a CHO cell line in high
      throughput and at large scale.
AB  - Transient expression of heterologous proteins in mammalian systems is a powerful
      way to generate protein reagents quickly. However, it has historically suffered
      from poor yields in comparison to methods where the recombinant gene is stably
      integrated into the genome and high expressing clones isolated. Transient methods
      have been well described for HEK-based systems. In this paper we show the use of
      a design of experiments (DoE) approach to quickly analyse the effect of a range
      of different parameters on protein expression from a CHO-based transient system.
      We show that this system is amenable to a very simple transfection procedure by
      independent direct addition of DNA and transfection reagent to the culture
      vessel. In addition we show that expression can be improved by reducing the
      temperature of the culture conditions post-transfection. The process is
      demonstrated to be transferrable from 3 ml cultures in deep 24-well plates
      through cultures in CultiFlask Bioreactors, shake flasks and up to 25 L culture
      in Wave Bioreactors. Data are shown to illustrate the utility of the system with
      a number of different classes of protein.

PMID- 26291268
TI  - Improving the activity of the subtilisin nattokinase by site-directed mutagenesis
      and molecular dynamics simulation.
AB  - Nattokinase (NK), a bacterial serine protease from Bacillus subtilis var. natto,
      is a potential cardiovascular drug exhibiting strong fibrinolytic activity. To
      broaden its commercial and medical applications, we constructed a single-mutant
      (I31L) and two double-mutants (M222A/I31L and T220S/I31L) by site-directed
      mutagenesis. Active enzymes were expressed in Escherichia coli with periplasmic
      secretion and were purified to homogeneity. The kinetic parameters of enzymes
      were examined by spectroscopy assay and isothermal titration calorimetry (ITC),
      and their fibrinolytic activities were determined by fibrin plate method. The
      substitution of Leu(31) for Ile(31) resulted in about 2-fold enhancement of
      catalytic efficiency (Kcat/KM) compared with wild-type NK. The specific
      activities of both double-mutants (M222A/I31L and T220S/I31L) were significantly
      increased when compared with the single-mutants (M222A and T220S) and the
      oxidative stability of M222A/I31L mutant was enhanced with respect to wild-type
      NK. This study demonstrates the feasibility of improving activity of NK by site
      directed mutagenesis and shows successful protein engineering cases to improve
      the activity of NK as a potent therapeutic agent. 

PMID- 26291273
TI  - Misspelled Author Name.

PMID- 26291270
TI  - New chemical tools to probe cell wall biosynthesis in bacteria.
AB  - Some of the most successful drugs in the antibiotic pharmacopeia are those that
      inhibit bacterial cell wall biosynthesis. However, the worldwide spread of
      bacterial antibiotic resistance has eroded the clinical efficacy of these drugs
      and the antibiotic pipeline continues to be lean as drug discovery programs
      struggle to bring new agents to the clinic. Nevertheless, cell wall biogenesis
      remains a high interest and celebrated target. Recent advances in the preparation
      of chemical probes and biosynthetic intermediates provide the tools necessary to
      better understand cell wall assembly. Likewise, these tools offer new
      opportunities to identify and evaluate novel biosynthetic inhibitors. This review
      aims to highlight these advancements and to provide context for their utility as
      innovative new tools to study cell wall biogenesis and for antibacterial drug
      discovery. 

PMID- 26291274
TI  - Mechanical characterization of aortic valve tissues using an inverse analysis
      approach.

PMID- 26291275
TI  - Characterization of Pain in Familial Amyloid Polyneuropathy.
AB  - Familial amyloid polyneuropathy (FAP) caused by transthyretin (TTR) mutation is a
      small-fiber predominant polyneuropathy, exposing patients with TTR-FAP to
      development of neuropathic pain. However, the painful nature of TTR-FAP has never
      been specifically addressed. In this study, we compared 2 groups of 16 patients
      with either painless or painful TTR-FAP with regard to various clinical and
      neurophysiologic variables, including laser evoked potential (LEP) recording and
      quantitative sensory testing. The 2 groups of patients did not differ on any
      clinical or neurophysiologic variable. Patients with painful TTR-FAP complained
      of ongoing burning pain sensations, pain aggravation at rest, paroxysmal pain
      (electric shock and stabbing sensations), or provoked pain (mostly dynamic
      mechanical allodynia). However, the symptomatic presentation of painful TTR-FAP
      evolved with the course of the disease. The duration of the disease and the
      severity of small-fiber lesions (increase in thermal thresholds and reduction in
      LEP amplitude) correlated negatively with the intensity of ongoing burning
      sensations and positively with the intensity of paroxysmal pain. In addition,
      small-fiber preservation correlated positively with cold allodynia and pain
      aggravation at rest and negatively with dynamic mechanical allodynia. Peripheral
      sensitization of small-diameter nociceptive axons might occur in early TTR-FAP
      and be responsible for the burning sensation and cold allodynia. As
      polyneuropathy and small-fiber loss progress, paroxysmal pain and dynamic
      mechanical allodynia may develop as a result of central sensitization generated
      by abnormal activities affecting relatively spared large-diameter sensory fibers.
      PERSPECTIVE: Pain in TTR-FAP includes several mechanisms varying with the course
      of the disease and the involvement of the different types of nerve fibers.

PMID- 26291277
TI  - Human primary erythroid cells as a more sensitive alternative in vitro
      hematological model for nanotoxicity studies: Toxicological effects of silver
      nanoparticles.
AB  - Although immortalized cells established from cancerous cells have been widely
      used for studies in nanotoxicology studies, the reliability of the results
      derived from immortalized cells has been questioned because of their different
      characteristics from normal cells. In the present study, human primary erythroid
      cells in liquid culture were used as an in vitro hematological cell model for
      investigation of the nanotoxicity of silver nanoparticles (AgNPs) and comparing
      the results to the immortalized hematological cell lines HL60 and K562. The AgNPs
      caused significant cytotoxic effects in the primary erythroid cells, as shown by
      the decreased cell viability and induction of intracellular ROS generation and
      apoptosis, whereas they showed much lower cytotoxic and apoptotic effects in HL60
      and K562 cells and did not induced ROS generation in these cell lines. Scanning
      electron microcopy revealed an interaction of AgNPs to the cell membrane in both
      primary erythroid and immortalized cells. In addition, AgNPs induced hemolysis in
      the primary erythroid cells in a dose-dependent manner, and transmission electron
      microcopy analysis revealed that AgNPs damaged the erythroid cell membrane. Taken
      together, these results suggest that human primary erythroid cells in liquid
      culture are a more sensitive alternative in vitro hematological model for
      nanotoxicology studies. 

PMID- 26291276
TI  - Frequency of Hospitalizations for Pain and Association With Altered Brain Network
      Connectivity in Sickle Cell Disease.
AB  - Sickle cell disease (SCD) is a hemoglobinopathy that affects more than 100,000
      individuals in the United States. The disease is characterized by the presence of
      sickle hemoglobin and recurrent episodes of pain. Some individuals with SCD
      experience frequent hospitalizations and a high burden of pain. The role of
      central mechanisms in SCD pain has not been explored. Twenty-five adolescents and
      young adults with SCD underwent functional magnetic resonance imaging.
      Participants were stratified into groups with high pain or low pain based on the
      number of hospitalizations for pain in the preceding 12 months. Resting state
      functional connectivity was analyzed using seed-based and dual regression
      independent component analysis. Intrinsic brain connectivity was compared between
      the high pain and low pain groups, and association with fetal hemoglobin, a known
      modifier of SCD, was explored. Patients in the high pain group displayed an
      excess of pronociceptive connectivity such as between anterior cingulate and
      default mode network structures, such as the precuneus, whereas patients in the
      low pain group showed more connectivity to antinociceptive structures such as the
      perigenual and subgenual cingulate. Although a similar proportion of patients in
      both groups reported that they were on hydroxyurea, the fetal hemoglobin levels
      were significantly higher in the low pain group and were associated with greater
      connectivity to antinociceptive structures. These findings support the role of
      central mechanisms in SCD pain. Intrinsic brain connectivity should be explored
      as a complementary and objective outcome measure in SCD pain research.
      PERSPECTIVE: Altered connectivity patterns associated with high pain experience
      in patients with sickle cell disease suggest a possible role of central
      mechanisms in sickle cell pain. Resting state brain connectivity studies should
      be explored as an effective methodology to investigate pain in SCD.

PMID- 26291278
TI  - Coordinated regulation of Nrf2 and histone H3 serine 10 phosphorylation in
      arsenite-activated transcription of the human heme oxygenase-1 gene.
AB  - Expression of the antioxidant gene heme oxygenase-1 (HO-1) is primarily induced
      through NF-E2-related factor 2 (Nrf2)-mediated activation of the antioxidant
      response element (ARE). Gene transcription is coordinately regulated by
      transcription factor activity at enhancer elements and epigenetic alterations
      such as the posttranslational modification of histone proteins. However, the role
      of histone modifications in the Nrf2-ARE axis remains largely uncharacterized.
      The environmental contaminant arsenite is a potent inducer of both HO-1
      expression and phosphorylation of histone H3 serine 10 (H3S10); therefore, we
      investigated the relationships between Nrf2 and H3S10 phosphorylation in arsenite
      induced, ARE-dependent, transcriptional activation of the human HO-1 gene.
      Arsenite increased phosphorylation of H3S10 both globally and at the HO-1
      promoter concomitantly with HO-1 transcription in human HaCaT keratinocytes.
      Conversely, arsenite-induced H3S10 phosphorylation and HO-1 expression were
      blocked by N-acetylcysteine (NAC), the c-Jun N-terminal kinase (JNK) inhibitor
      SP600125, and JNK knockdown (siJNK). Interestingly, ablation of arsenite-induced
      H3S10 phosphorylation by SP600125 or siJNK did not inhibit Nrf2 nuclear
      accumulation nor ARE binding, despite inhibiting HO-1 expression. In response to
      arsenite, binding of Nrf2 to the HO-1 ARE preceded phosphorylation of H3S10 at
      the HO-1 ARE. Furthermore, arsenite-mediated occupancy of phosphorylated H3S10 at
      the HO-1 ARE was decreased in Nrf2-deficient mouse embryonic fibroblasts. These
      results suggest the involvement of H3S10 phosphorylation in the Nrf2-ARE axis by
      proposing that Nrf2 may influence H3S10 phosphorylation at the HO-1 ARE and
      additional promoter regions. Our data highlights the complex interplay between
      Nrf2 and H3S10 phosphorylation in arsenite-activated HO-1 transcription. 

PMID- 26291279
TI  - SS-31 attenuates TNF-alpha induced cytokine release from C2C12 myotubes.
AB  - TNF-alpha is a key inflammatory mediator and is proposed to induce
      transcriptional responses via the mitochondrial generation of Reactive Oxygen
      Species (ROS). The aim of this study was to determine the effect of TNF-alpha on
      the production of myokines by skeletal muscle. Significant increases were seen in
      the release of IL-6, MCP-1/CCL2, RANTES/CCL5 and KC/CXCL1 and this release was
      inhibited by treatment with Brefeldin A, suggesting a golgi-mediated release of
      cytokines by muscle cells. An increase was also seen in superoxide in response to
      treatment with TNF-alpha, which was localised to the mitochondria and this was
      also associated with activation of NF-kappaB. The changes in superoxide,
      activation of NF-kB and release of myokines were attenuated following pre
      treatment with SS-31 peptide indicating that the ability of TNF-alpha to induce
      myokine release may be mediated through mitochondrial superoxide, which is, at
      least in part, associated with activation of the redox sensitive transcription
      factor NF-kB. 

PMID- 26291280
TI  - Development and validation of a simplified Stroke-Thrombolytic Predictive
      Instrument.
AB  - OBJECTIVES: The Stroke-Thrombolytic Predictive Instrument (Stroke-TPI) predicts
      the probability of good and bad outcomes with and without recombinant tissue
      plasminogen activator (rtPA). We sought to rebuild and externally validate a
      simpler Stroke-TPI to support implementation in routine clinical care. METHODS:
      Using the original derivation cohort of 1,983 patients from a combined database
      of randomized clinical trials (NINDS [National Institute of Neurological
      Disorders and Stroke] 1 and 2; ATLANTIS [Alteplase Thrombolysis for Acute
      Noninterventional Therapy in Ischemic Stroke] A and B; and ECASS [European
      Cooperative Acute Stroke Study] II), we simplified the Stroke-TPI by reducing
      variables and interaction terms and by exploring simpler (3- and 8-item) stroke
      severity scores. External validation was performed in the ECASS III trial (n =
      821). RESULTS: The following 6 variables were most predictive of good outcomes:
      age, systolic blood pressure, diabetes, stroke severity, symptom onset to
      treatment time, and rtPA therapy. Treatment effect modifiers included onset to
      treatment time and systolic blood pressure. For the models predicting a bad
      outcome (modified Rankin Scale [mRS] score >=5), significant variables included
      age, stroke severity, and serum glucose. rtPA therapy did not change the risk of
      a poor outcome. Compared with models using the full NIH Stroke Scale, models
      using the 3-item severity score showed similar discrimination and excellent
      calibration. External validation on ECASS III showed similar performance (C
      statistics 0.75 [mRS score <=1] and 0.80 [mRS score <=2]). CONCLUSION: A simpler
      model using a 3-item stroke severity score, instead of the 15-item NIH Stroke
      Scale, has similar prognostic value and may be easier to use in routine care.
      Future studies are needed to test whether it can improve process and clinical
      outcomes.

PMID- 26291281
TI  - Salivary cortisol, brain volumes, and cognition in community-dwelling elderly
      without dementia.
AB  - OBJECTIVE: We investigated the associations of morning and evening salivary
      cortisol levels with regional brain volumes and cognitive functioning in
      community-dwelling older persons without dementia. METHOD: From the Age,
      Gene/Environment Susceptibility (AGES)-Reykjavik Study, we included 4,244 persons
      without dementia (age 76 +/- 5 years, 58% women) who had 1.5T brain MRI,
      assessment of cognitive functioning, and saliva collected at home 45 minutes
      after awakening and at night. Linear regression analysis was used to estimate the
      cross-sectional relationship among cortisol levels, brain volumes, and cognitive
      functioning, adjusting for covariates. RESULTS: Higher evening cortisol was
      associated with smaller total brain volume (highest vs lowest tertile -16.0 mL;
      95% confidence interval -19.7 to -12.2 mL, adjusted for age, sex, education,
      intracranial volume, smoking, steroid use, white matter lesions, and brain
      infarcts on MRI). The smaller volumes were observed in all brain regions, but
      were significantly smaller in gray matter than in white matter regions. Poorer
      cognitive functioning across all domains was also associated with higher evening
      cortisol. Higher levels of morning cortisol were associated with slightly greater
      normal white matter volume and better processing speed and executive functioning,
      but not with gray matter volume or with memory performance. CONCLUSIONS: In older
      persons, evening and morning cortisol levels may be differentially associated
      with tissue volume in gray and white matter structures and cognitive function.
      Understanding these differential associations may aid in developing strategies to
      reduce the effects of hypothalamic-pituitary-adrenal axis dysfunction on late
      life cognitive impairment.

PMID- 26291282
TI  - Acute headache diagnosis in pregnant women: a hospital-based study.
AB  - OBJECTIVE: To characterize demographic and clinical features in pregnant women
      presenting with acute headache, and to identify clinical features associated with
      secondary headache. METHODS: We conducted a 5-year, single-center, retrospective
      study of consecutive pregnant women presenting to acute care with headache
      receiving neurologic consultation. RESULTS: The 140 women had a mean age of 29 +/
      6.4 years and often presented in the third trimester (56.4%). Diagnoses were
      divided into primary (65.0%) and secondary (35.0%) disorders. The most common
      primary headache disorder was migraine (91.2%) and secondary headache disorders
      were hypertensive disorders (51.0%). The groups were similar in demographics,
      gestational ages, and most headache features. In univariate analysis, secondary
      headaches were associated with a lack of headache history (36.7% vs 13.2%, p =
      0.0012), seizures (12.2% vs 0.0%, p = 0.0015), elevated blood pressure (55.1% vs
      8.8%, p < 0.0001), fever (8.2% vs 0.0%, p = 0.014), and an abnormal neurologic
      examination (34.7% vs 16.5%, p = 0.014). In multivariate logistic regression,
      elevated blood pressure (odds ratio [OR] 17.0, 95% confidence interval [CI] 4.2
      56.0) and a lack of headache history (OR 4.9, 95% CI 1.7-14.5) had an increased
      association with secondary headache, while psychiatric comorbidity (OR 0.13, 95%
      CI 0.021-0.78) and phonophobia (OR 0.29, 95% CI 0.09-0.91) had a reduced
      association with secondary headache. CONCLUSIONS: Among pregnant women receiving
      inpatient neurologic consultation, more than one-third have secondary headache.
      Diagnostic vigilance should be heightened in the absence of a headache history
      and if seizures, hypertension, or fever are present. Attack features may not
      adequately distinguish primary vs secondary disorders, and low thresholds for
      neuroimaging and monitoring for preeclampsia are justified.

PMID- 26291283
TI  - Disseminated cryptococcosis in a patient with multiple sclerosis treated with
      fingolimod.

PMID- 26291286
TI  - Habenula: Recently recognized functions and potential clinical relevance.

PMID- 26291284
TI  - SCN2A encephalopathy: A major cause of epilepsy of infancy with migrating focal
      seizures.
AB  - OBJECTIVE: De novo SCN2A mutations have recently been associated with severe
      infantile-onset epilepsies. Herein, we define the phenotypic spectrum of SCN2A
      encephalopathy. METHODS: Twelve patients with an SCN2A epileptic encephalopathy
      underwent electroclinical phenotyping. RESULTS: Patients were aged 0.7 to 22
      years; 3 were deceased. Seizures commenced on day 1-4 in 8, week 2-6 in 2, and
      after 1 year in 2. Characteristic features included clusters of brief focal
      seizures with multiple hourly (9 patients), multiple daily (2), or multiple
      weekly (1) seizures, peaking at maximal frequency within 3 months of onset.
      Multifocal interictal epileptiform discharges were seen in all. Three of 12
      patients had infantile spasms. The epileptic syndrome at presentation was
      epilepsy of infancy with migrating focal seizures (EIMFS) in 7 and Ohtahara
      syndrome in 2. Nine patients had improved seizure control with sodium channel
      blockers including supratherapeutic or high therapeutic phenytoin levels in 5.
      Eight had severe to profound developmental impairment. Other features included
      movement disorders (10), axial hypotonia (11) with intermittent or persistent
      appendicular spasticity, early handedness, and severe gastrointestinal symptoms.
      Mutations arose de novo in 11 patients; paternal DNA was unavailable in one.
      CONCLUSIONS: Review of our 12 and 34 other reported cases of SCN2A encephalopathy
      suggests 3 phenotypes: neonatal-infantile-onset groups with severe and
      intermediate outcomes, and a childhood-onset group. Here, we show that SCN2A is
      the second most common cause of EIMFS and, importantly, does not always have a
      poor developmental outcome. Sodium channel blockers, particularly phenytoin, may
      improve seizure control.

PMID- 26291285
TI  - Anti-DPPX encephalitis: pathogenic effects of antibodies on gut and brain
      neurons.
AB  - OBJECTIVE: To characterize pathogenic effects of antibodies to dipeptidyl
      peptidase-like protein 6 (DPPX), a subunit of Kv4.2 potassium channels, on gut
      and brain neurons. METHODS: We identified a new patient with anti-DPPX
      encephalitis and analyzed the effects of the patient's serum and purified
      immunoglobulin G (IgG), and of serum of a previous patient with anti-DPPX
      encephalitis, on the activity of enteric neurons by voltage-sensitive dye imaging
      in guinea pig myenteric and human submucous plexus preparations. We studied the
      subcellular localization of DPPX by immunocytochemistry in cultured murine
      hippocampal neurons using sera of 4 patients with anti-DPPX encephalitis. We
      investigated the influence of anti-DPPX-containing serum and purified IgG on
      neuronal surface expression of DPPX and Kv4.2 by immunoblots of purified murine
      hippocampal neuron membranes. RESULTS: The new patient with anti-DPPX
      encephalitis presented with a 2-month episode of diarrhea, which was followed by
      tremor, disorientation, and mild memory impairment. Anti-DPPX-IgG-containing sera
      and purified IgG increased the excitability and action potential frequency of
      guinea pig and human enteric nervous system neurons. Patient sera revealed a
      somatodendritic and perisynaptic neuronal surface staining that colocalized with
      the signal of commercial anti-DPPX and Kv4.2 antibodies. Incubation of
      hippocampal neurons with patient serum and purified IgG resulted in a decreased
      expression of DPPX and Kv4.2 in neuronal membranes. CONCLUSIONS:
      Hyperexcitability of enteric nervous system neurons and downregulation of DPPX
      and Kv4.2 from hippocampal neuron membranes mirror the clinical phenotype of
      patients with anti-DPPX encephalitis and support a pathogenic role of anti-DPPX
      antibodies in anti-DPPX encephalitis.

PMID- 26291287
TI  - The experimental accuracy of the uni-directional exact NOE.
AB  - We have established protocols to calculate exact NOEs (eNOE) from NOE data. eNOEs
      lend unprecedented precision to the calculation of distance restraints used for
      structure calculation. Moreover, as eNOEs are averaged quantities over all
      conformations of a molecule, they may contain accessible information of the
      sampled conformational space. In practice, a prerequisite for an exact
      interpretation is the evaluation of both NOESY cross-peak buildups. For large
      molecular sizes, the fraction of NOEs which can only be obtained from one cross
      peak typically increases. Distance restraints derived from such NOEs must be used
      with a tolerance for errors associated with the broken symmetry of the individual
      magnetization transfer pathways. The correct choice of upper and lower limits is
      particularly important for multiple-state ensemble calculation, where too narrow
      tolerances may lead to incorrect spatial sampling. In order to dissect these
      pathways in heavy-atom resolved 3D NOESY experiments, we analyze 2D [(1)H, (1)H]
      NOESY experiments, which are the fundamental building blocks of the former. In
      combination with an analysis of excitation and inversion profiles of pulses on
      heavy atoms and relaxation effects during HXQC elements, we derive a rule for the
      correct choice of upper and lower distance limits derived from such uni
      directional NOEs. We show that normalization of the cross- to the diagonal-peak
      intensities of the spins of magnetization destination rather than origin leads to
      similar errors of the distance restraints. This opens up the prospect of extended
      collection of unidirectional eNOEs. 

PMID- 26291288
TI  - A behavioral study of the nature of verb production deficits in Alzheimer's
      disease.
AB  - Patients with Alzheimer's disease (AD) may experience greater difficulty with
      verb production than with noun production. In this study, we sought to assess the
      nature of verb production deficits in AD by using verb fluency and verb naming
      tasks. We designed two hypotheses for this verb deficit: (1) executive impairment
      drives the deficit; (2) semantic impairment drives the deficit. Thirty-five
      patients with AD and 35 matched healthy controls participated in the study. Both
      groups performed a verb naming task composed of 45 pictures (low-, medium-, and
      high-frequency subsets) and a verb fluency task (scored for total correct words
      and for mean word frequency). Patients with AD were equally impaired in verb
      naming and verb fluency, with an effect of disease severity on verb naming. Word
      frequency influenced verb naming, but not verb fluency, performance. Our results
      indicate that verb production deficits in AD seem to be driven more by semantic
      than by executive impairment. 

PMID- 26291290
TI  - Economic stressors and alcohol-related outcomes: exploring age cohort
      differences.
AB  - OBJECTIVES: This study examined processes linking age cohort, economic stressors,
      coping strategies and two drinking-related outcomes (i.e., past-month drinking
      and problematic drinking). METHODS: Structural equation models were conducted
      utilizing data from a national survey. RESULTS: Findings revealed the
      associations between economic stressors and both past-month drinking and
      problematic drinking were significantly greater for members of the millennial
      cohort compared to baby boomers. These effects are partly explained by the lesser
      tendency of members of the millennial cohort to use collective, politically
      focused coping strategies. DISCUSSION: These findings clarify the circumstances
      in which age matters most for the associations among economy-related stressors,
      coping strategies and drinking-related outcomes. They highlight how difficult
      economic circumstances influence the availability of coping strategies and, in
      turn, alcohol consumption - and differently for younger and older age cohorts.

PMID- 26291289
TI  - Specifying the role of the left prefrontal cortex in word selection.
AB  - Word selection allows us to choose words during language production. This is
      often viewed as a competitive process wherein a lexical representation is
      retrieved among semantically-related alternatives. The left prefrontal cortex
      (LPFC) is thought to help overcome competition for word selection through top
      down control. However, whether the LPFC is always necessary for word selection
      remains unclear. We tested 6 LPFC-injured patients and controls in two picture
      naming paradigms varying in terms of item repetition. Both paradigms elicited the
      expected semantic interference effects (SIE), reflecting interference caused by
      semantically-related representations in word selection. However, LPFC patients as
      a group showed a larger SIE than controls only in the paradigm involving item
      repetition. We argue that item repetition increases interference caused by
      semantically-related alternatives, resulting in increased LPFC-dependent
      cognitive control demands. The remaining network of brain regions associated with
      word selection appears to be sufficient when items are not repeated. 

PMID- 26291291
TI  - Evaluating the accuracy of alcohol expectancies relative to subjective response
      to alcohol.
AB  - INTRODUCTION: Although limited in empirical support, Alcohol Expectancy (AE)
      theory posits that AEs may overestimate subjective response (SR) to the positive
      effects of alcohol, which, in turn, confers alcohol-related risk (e.g., Darkes &
      Goldman, 1993). The recent development of the Anticipated Effects of Alcohol
      Scale (AEAS; Morean, Corbin, & Treat, 2012) and the Subjective Effects of Alcohol
      Scale (SEAS; Morean, Corbin, & Treat, 2013) now permits direct AE-SR comparisons
      using psychometrically sound assessments designed for this purpose. METHODS: We
      ran secondary data analyses (Morean et al., 2012, 2013) evaluating measurement
      invariance of AEs and SR; AE-SR relationships; the accuracy of AEs; and relations
      between AE-SR discrepancies and binge drinking, driving after drinking, and
      alcohol-related problems in a sample of 102 young adults (mean age 22.81 [2.25];
      74.5% male; 76.5% Caucasian) who consumed alcohol in a simulated bar setting
      (target blood alcohol level=.08g/dL). RESULTS: The AEAS and SEAS were scalar
      measurement invariant and that AEs generally overestimated SR (mean Cohen's
      d=.48). Relative to SR, inflated high arousal negative AEs (e.g., aggressive)
      were associated with frequent binge drinking and alcohol-related problems,
      whereas exaggerated low arousal negative AEs (e.g., woozy) served protective
      functions. As blood alcohol levels rose, inflated low arousal positive AEs (e.g.,
      relaxed) and low arousal negative AEs (e.g., wobbly) were associated with less
      frequent driving after drinking. CONCLUSIONS: Challenging AE-SR discrepancies for
      high arousal effects may have utility in treatment and prevention efforts,
      whereas maintaining overestimates of low arousal effects may serve protective
      functions.

PMID- 26291292
TI  - Lymphadenopathy and Jaundice.

PMID- 26291293
TI  - Relative Composition of Fibrous Connective and Fatty/Glandular Tissue in
      Connective Tissue Grafts Depends on the Harvesting Technique but not the Donor
      Site of the Hard Palate.
AB  - BACKGROUND: Whether the composition of palatal connective tissue grafts (CTGs)
      varies depending on donor site or harvesting technique in terms of relative
      amounts of fibrous connective tissue (CT) and fatty/glandular tissue (FGT) is
      currently unknown and is histologically assessed in the present study. METHODS:
      In 10 fresh human cadavers, tissue samples were harvested in the anterior and
      posterior palate and in areas close to (marginal) and distant from (apical) the
      mucosal margin. Mucosal thickness, lamina propria thickness (defined as the
      extent of subepithelial portion of the biopsy containing <=25% or <=50% FGT), and
      proportions of CT and FGT were semi-automatically estimated for the entire mucosa
      and for CTGs virtually harvested by split-flap (SF) preparation minimum 1 mm deep
      or after deepithelialization (DE). RESULTS: Palatal mucosal thickness, ranging
      from 2.35 to 6.89 mm, and histologic composition showed high interindividual
      variability. Lamina propria thickness (P >0.21) and proportions of CT (P = 0.48)
      and FGT (P = 0.15) did not differ significantly among the donor sites (anterior,
      posterior, marginal, apical). However, thicker palatal tissue was associated with
      higher FGT content (P <0.01) and thinner lamina propria (P <=0.03). Independent
      of the donor site, DE-harvested CTG contained a significantly higher proportion
      of CT and a lower proportion of FGT than an SF-harvested CTG (P <0.04).
      CONCLUSION: Despite high interindividual variability in terms of relative tissue
      composition in the hard palate, DE-harvested CTG contains much larger amounts of
      CT and much lower amounts of FGT than SF-harvested CTG, irrespective of the
      harvesting site.

PMID- 26291294
TI  - Use of Fractal Analysis for the Discrimination of Trabecular Changes Between
      Individuals With Healthy Gingiva or Moderate Periodontitis.
AB  - BACKGROUND: The aim of this study is to evaluate the capability of fractal
      analysis to discriminate the changes in the trabecular structure of interdental
      bone between individuals with healthy gingiva or moderate periodontitis using
      digital images. METHODS: Two groups of patients were included according to the
      probing depth, bleeding on probing, and clinical attachment level. The first
      group (n = 50) consisted of individuals with healthy gingiva, whereas the other
      group consisted of patients with moderate periodontitis (n = 50). Periapical
      images obtained with a storage phosphor plate system during clinical examination
      were used for the fractal dimension (FD) calculations. Two rectangular regions of
      interest (ROIs) were placed at mandibular posterior interdental bone areas. The
      mean of the two ROIs was used to calculate mean FD by using the box-counting
      method. Student t test was used for the comparison of the FDs of the two groups
      (P = 0.05). RESULTS: The mean FD of patients with periodontitis was 0.83, whereas
      it was 1.02 for the patients with healthy gingiva. A significant difference was
      obtained in the mean FD values of healthy individuals and patients with moderate
      periodontitis (P <0.05). CONCLUSION: Fractal analysis can quantitatively
      discriminate the trabecular integrity alterations induced by periodontitis and
      therefore can be recommended for the diagnosis and monitoring of changes in
      trabecular architecture associated with periodontitis.

PMID- 26291295
TI  - Effect of Doxycycline in Gel Form on Bone Regeneration: Histomorphometric and
      Tomographic Study in Rat Calvaria.
AB  - BACKGROUND: This study aims to investigate the effects of the local application
      of doxycycline in the form of natrosol-based gel on bone regeneration by
      examining critical defects in rat calvaria. METHODS: Twenty-four rats were
      randomly divided into three groups with eight animals each, according to the
      treatment received: BC (untreated, filled with blood clot), NAT (natrosol gel
      alone), and DOX (10% doxycycline gel). Four animals from each group were
      euthanized at 4 and 8 weeks postoperatively. In tomographic analysis, mean
      density in the region of the defect was calculated as a percentage relative to
      the native bone density. In histomorphometric analysis, the newly formed bone
      area was calculated as a percentage of the total area. The values obtained
      underwent analysis of variance and Tukey testing (P <0.05). RESULTS: The mean
      percentage of tomographic density in the region of the defect at the end of 8
      weeks was higher for DOX (44.37%), and statistical differences in this period
      were observed between DOX and NAT (33.10%) and DOX and BC (32.43%). Regarding new
      bone formation, at the end of 8 weeks, DOX (61.11%) also had the highest mean
      bone formation, and statistical differences were observed between DOX and NAT
      (34.61%) and DOX and BC (23.11%). CONCLUSION: It was observed that 10%
      doxycycline gel had a good effect on bone regeneration regarding the filling of
      critical defects in rat calvaria.

PMID- 26291296
TI  - Chronic Periodontitis Is Associated With Spinal Dysmobility in Patients With
      Ankylosing Spondylitis.
AB  - BACKGROUND: Although microbes have been suggested to play a role in the
      pathogenesis of ankylosing spondylitis (AS), several studies present
      contradictory results regarding the association between AS and chronic
      periodontitis (CP). METHODS: Clinical, laboratory, and medication data were
      collected from 84 patients with AS and 84 age- and sex-matched controls.
      Periodontal measurements, including probing depths (PDs), clinical attachment
      loss (AL), serum anti-Porphyromonas gingivalis titers, and the detection of P.
      gingivalis DNA in gingival crevicular fluid, were recorded. All participants with
      periodontitis with PD >=4 to <7 mm received scaling and root planing and were re
      evaluated at 12 weeks; those still exhibiting periodontitis with PD of >=4 to <7
      mm at 12 weeks were followed at 24 weeks. RESULTS: The prevalence of moderate-to
      severe CP was not different between patients with AS and controls (70.2% versus
      66.6%). The P. gingivalis detection rate was not different between patients with
      AS and controls or between patients with AS receiving and not receiving anti
      tumor necrosis factor (TNF)-alpha agents. However, CP was positively associated
      with impaired spinal mobility of patients with AS in multivariate analyses. After
      periodontal treatment, PD and AL levels were improved in both groups, but the
      change was significantly greater in patients with AS than in controls. Patients
      with AS receiving anti-TNF-alpha agents exhibited a greater improvement in PD and
      AL than those who did not. CONCLUSIONS: Although AS was not associated with the
      presence of CP, CP was associated positively with the severity of spinal
      dysmobility in Korean patients with AS. These results suggest that periodontitis
      can have a negative effect on axial movement in AS.

PMID- 26291297
TI  - Microbiologic Findings in Relation to Risk Assessment for Periodontal Disease: A
      Cross-Sectional Study.
AB  - BACKGROUND: In this study, an association between a computerized risk calculator
      and microbiologic testing is examined in patients with periodontitis. METHODS:
      Seventy-four patients with moderate and severe periodontitis were selected from
      patients receiving treatment at Tufts University School of Dental Medicine. Their
      periodontal risk was analyzed with a periodontitis risk assessment tool, and
      microbiologic testing was performed. Periodontitis risk assessment and
      microbiologic testing were examined for a possible association. The data were
      evaluated by the chi(2) test at P <0.05 levels. RESULTS: Forty-six patients
      scored as having a "very high" risk of periodontitis and 22 patients scored as
      having a "high" risk of periodontitis by the risk assessment tool. Patients with
      a risk score of very high risk showed a higher detection of each bacterium except
      Capnocytophaga species than the rest of the study population. Treponema denticola
      and Prevotella intermedia (P = 0.01 and P = 0.02, respectively) were two bacteria
      that showed a statistically significant difference between patients at very high
      risk and those at high risk. CONCLUSIONS: Patients with periodontitis were
      identified as high risk and very high risk compared with the rest of the risk
      categories by the risk assessment tool. The study population, categorized mostly
      as very high risk, showed high detection of putative periodontal bacteria.

PMID- 26291298
TI  - Interfacial structure and wetting properties of water droplets on graphene under
      a static electric field.
AB  - The behavior of water droplets located on graphene in the presence of various
      external electric fields (E-fields) is investigated using classical molecular
      dynamics (MD) simulations. We explore the effect of E-field on mass density
      distribution, water polarization as well as hydrogen bonds (H-bonds) to gain
      insight into the wetting properties of water droplets on graphene and their
      interfacial structure under uniform E-fields. The MD simulation results reveal
      that the equilibrium water droplets present a hemispherical, a conical and an
      ordered cylindrical shape with the increase of external E-field intensity.
      Accompanied by the shape variation of water droplets, the dipole orientation of
      water molecules experiences a remarkable change from a disordered state to an
      ordered state because of the polarization of water molecules induced by static E
      field. The distinct two peaks in mass density and H-bond distribution profiles
      demonstrate that water has a layering structure in the interfacial region, which
      sensitively depends on the strong E-field (>0.8 V nm(-1)). In addition, when the
      external E-field is parallel to the substrate, the E-field would make the contact
      angle of the water droplets become small and increase its wettability. Our
      findings provide the possibility to control the structure and wetting properties
      of water on graphene by tuning the direction and intensity of external E-field
      which is of importance for relevant industrial processes on the solid surface. 

PMID- 26291299
TI  - Comment and reply on: Guidelines for the management of spontaneous preterm labor:
      identification of spontaneous preterm labor, diagnosis of preterm premature
      rupture of membranes, and preventive tools for preterm birth.

PMID- 26291300
TI  - The influence of obstetric variables on school achievement, intelligence and
      neuropsychological development in a sample of Spanish twins at the age of six: a
      retrospective study.
AB  - OBJECTIVES: The increasing number of multiple pregnancies in recent years has
      raised a particular concern about the problems associated to these pregnancies.
      It still remains unclear whether twin deliveries, as currently conceived, provide
      the same future health chances to both fetuses. In this regard, it is worth
      mentioning that the effects of obstetric and neonatal care beyond the perinatal
      period have not often been evaluated. The main objective of this research was to
      analyze the impact of obstetric and perinatal variables on postnatal
      neuropsychological development, intelligence and school achievement of twin
      children. METHODS: We conducted a cross-sectional and observational study on 62
      pairs of 6-year-old twins, who were on their first year of primary education. All
      124 children and their mother were individually assessed and perinatal clinical
      data were collected. A stratified multivariate analysis was performed using
      multiple linear regressions. RESULTS: The type of birth was the best predicting
      variable, so that the best results were achieved in children born in spontaneous
      vaginal deliveries. Comparatively, however, poorer scores were seen in males
      second twins born by the vaginal route in spatial structuring, non-verbal
      development and total development areas, especially in case of delivery before 37
      weeks. CONCLUSIONS: Our study confirms the impact of some obstetric variables on
      school achievement and psychological development of twins.

PMID- 26291301
TI  - Atypical acute respiratory disorder in late preterm  and term newborn infants.
AB  - OBJECTIVE: We were to describe the clinical characteristics of late preterm and
      term newborn infants who needed invasive or non-invasive ventilation for
      respiratory distress but did not meet the diagnostic criteria of common neonatal
      respiratory disorders (atypical acute respiratory disorder; aRD). METHODS: We
      retrospectively reviewed electronic medical records of 242 late preterm and term
      newborn infants born who were admitted to the neonatal intensive care unit for
      acute respiratory distress developed within 24 h after birth. RESULTS: Newborn
      infants with aRD had significantly higher mean, maximum blood PCO2 levels and
      maximum FiO2 levels during the first 72 h after birth than infants with transient
      tachypnea of the newborn (TTN). Total periods of oxygen supplementation of the
      infants with aRD were significantly longer than those of infants with TTN, but
      shorter than those of the infants with meconium aspiration syndrome (MAS).
      CONCLUSIONS: Except for definite diagnosis, higher oxygen need and PCO2 level on
      blood gas analysis during the initial period of their respiratory illness may be
      able to predict aRD, and these interventions may be able to decrease neonatal
      respiratory morbidity.

PMID- 26291302
TI  - Intra-abdominal saline irrigation at cesarean  section: a systematic review and
      meta-analysis.
AB  - OBJECTIVE: The aim of this study was to examine the evidence guiding
      intraoperative saline irrigation at cesarean sections. METHODS: We searched
      "cesarean sections", "pregnancy", "saline irrigation" and "randomized clinical
      trials" in ClinicalTrials.gov, the Cochrane Central Register of Controlled
      Trials, AJOL, MEDLINE, LILACS and CINAHL from inception of each database to April
      2015. The primary outcomes were predefined as intraoperative nausea and emesis.
      The pooled results were reported as relative risk (RR) with 95% confidence
      interval (95% CI). RESULTS: Three randomized trials including 862 women were
      analyzed. Intraoperative saline irrigation was associated with a 68% increased
      risk of developing intraoperative nausea (RR = 1.68, 95% CI 1.36-2.06), 70%
      increased risk of developing intraoperative emesis (RR = 1.70, 95% CI 1.28-2.25),
      92% increased risk of developing post-operative nausea and 84% increased risk of
      using anti-emetics post-operatively (RR = 1.84, 95% CI 0.21-2.78) when compared
      with controls. There were no significant differences between intraoperative
      saline irrigation and no treatment for post-operative emesis (RR = 1.65, 95% CI
      0.74-3.67), estimated blood loss, time to return of gastrointestinal function,
      postpartum endometritis (RR = 0.95, 95% CI 0.64-1.40), urinary tract infection
      and wound infection. CONCLUSION: Intraoperative saline irrigation at cesarean
      delivery increases intraoperative and post-operative nausea, requiring increasing
      use of anti-emetics without significant reduction in infectious, intraoperative
      and postpartum complications. Routine abdominal irrigation at cesarean section is
      not supported by current data.

PMID- 26291304
TI  - A vanadium(IV) pyrazolate metal-organic polyhedron with permanent porosity and
      adsorption selectivity.
AB  - A vanadium(IV) pyrazolate-based open metal-organic polyhedron of [V3(MU3
      O)O(OH)2(MU4-BPD)1.5(MU-HCOO)3] (BDP = benzene-1,4-bipyrazolate) formulation
      gives rise to a porous crystal structure exhibiting micro and mesoporosity which
      is useful for selective adsorption of gases.

PMID- 26291303
TI  - Increase in Lymphadenitis Cases after Shift in BCG Vaccine Strain.

PMID- 26291305
TI  - What causes the weakest host to act as the strongest one? A theoretical study on
      the host-guest chemistry of five azacryptands and fluoride anions.
AB  - In this work we have attempted to computationally analyze the important
      parameters affecting the selectivity in host-guest systems in order to show that
      the solvent effect in some host-guest systems is even more important than the
      hole-size fitting and/or host-guest interaction energy. For this purpose, the
      fluoride anion selectivities of the five most studied azacryptands with different
      affinities, moieties, cavity sizes and degrees of preorganization, in their fully
      protonated forms, were studied at PBE/TZVP and B3P86/TZVP levels of theory. The
      factors affecting the selectivity such as hole size fitting, steric effects,
      electronic properties, preorganization of hosts, as well as solvent effects were
      investigated. The results showed that among the five studied azacryptands, one of
      them, which ranks fifth for selectivity according to its weak interaction energy
      with fluoride anions, ranks fourth due to its good preorganization. However, a
      surprising improvement occurs when its selectivity for fluoride anions ranks
      first due to the existence of less solvent hindrance. The results of the
      calculations were further confirmed by a good correlation between the calculated
      and experimental formation constants. 

PMID- 26291306
TI  - Synthesis of the cyanobacterial metabolite nostodione A, structural studies and
      potent antiparasitic activity against Toxoplasma gondii.
AB  - A total synthesis of the cyanobacterial natural product nostodione A is reported
      involving a convergent, diversity-oriented route, enabling the assembly of a mini
      library of structural analogues. The first single crystal X-ray structural
      determination on a member of this series is reported along with SAR studies
      identifying potent inhibitors of invasion and replication of the parasitic
      protozoan Toxoplasma gondii. 

PMID- 26291307
TI  - Robot-assisted primary cementless total hip arthroplasty with a short femoral
      stem: a prospective randomized short-term outcome study.
AB  - BACKGROUND: Recently, two topical issues in total hip arthroplasty (THA) have
      been robot-assisted surgery and use of a short stem. The purpose of this study
      was to evaluate the effects of robotic milling on the accuracy of short femoral
      stem positioning and on the short-term clinical outcome in THA using a
      prospective, randomized design. METHODS: We randomized 54 patients into two
      groups, either robotic milling group or manual rasping group. The patients were
      assessed clinically and radiographically at 8 weeks, 5 months, 12 months, and 24
      months. RESULTS: Robotic milling group had a significantly longer operation time,
      requiring on average 8.9 min for registration and 11.2 min for milling. On the
      other hand, robotic milling group showed superior results in terms of stem
      alignment and leg length equality. Two intraoperative femoral fractures occurred
      only in manual rasping group. Harris hip scores and WOMAC scores at 24 months
      postoperatively were similar in both groups. No complications including stem
      loosening, infection, nerve palsy, or dislocation were encountered in either
      group during the follow-up period. CONCLUSIONS: The present study suggested that
      robot-assisted short stem THA could increase the accuracy of stem alignment,
      improve leg length equality, and help reduce the risk of intraoperative femoral
      fracture as compared with manual rasping. However, the clinical outcome scores
      did not differ between the two groups at the time of short-term follow-up. Long
      term follow-up is needed to determine whether there will be a long-term clinical
      relevance of robot-assisted implantation of short femoral stems in THA.

PMID- 26291308
TI  - Fewer Bacteria Adhere to Softer Hydrogels.
AB  - Clinically, biofilm-associated infections commonly form on intravascular
      catheters and other hydrogel surfaces. The overuse of antibiotics to treat these
      infections has led to the spread of antibiotic resistance and underscores the
      importance of developing alternative strategies that delay the onset of biofilm
      formation. Previously, it has been reported that during surface contact, bacteria
      can detect surfaces through subtle changes in the function of their motors.
      However, how the stiffness of a polymer hydrogel influences the initial
      attachment of bacteria is unknown. Systematically, we investigated poly(ethylene
      glycol) dimethacrylate (PEGDMA) and agar hydrogels that were 20 times thicker
      than the cumulative size of bacterial cell appendages, as a function of Young's
      moduli. Soft (44.05-308.5 kPa), intermediate (1495-2877 kPa), and stiff (5152
      6489 kPa) hydrogels were synthesized. Escherichia coli and Staphylococcus aureus
      attachment onto the hydrogels was analyzed using confocal microscopy after 2 and
      24 h incubation periods. Independent of hydrogel chemistry and incubation time,
      E. coli and S. aureus attachment correlated positively to increasing hydrogel
      stiffness. For example, after a 24 h incubation period, there were 52 and 82%
      fewer E. coli adhered to soft PEGDMA hydrogels than to the intermediate and stiff
      PEGDMA hydrogels, respectively. A 62 and 79% reduction in the area coverage by
      the Gram-positive microbe S. aureus occurred after 24 h incubation on the soft
      versus intermediate and stiff PEGDMA hydrogels. We suggest that hydrogel
      stiffness is an easily tunable variable that could potentially be used
      synergistically with traditional antimicrobial strategies to reduce early
      bacterial adhesion and therefore the occurrence of biofilm-associated infections.

PMID- 26291309
TI  - Accuracy of White Blood Cell Count and C-reactive Protein Levels Related to
      Duration of Symptoms in Patients Suspected of Acute Appendicitis.
AB  - OBJECTIVES: Low levels of white blood cell (WBC) count and C-reactive protein
      (CRP) have been suggested to sufficiently rule out acute appendicitis. The
      diagnostic value of these tests is likely to depend on the duration of
      complaints. The aim of this study was to evaluate the accuracy of these
      inflammatory markers in relation to duration of symptoms in patients suspected of
      acute appendicitis. METHODS: Patients suspected of having acute appendicitis were
      retrospectively selected from five prospective cohorts of patients with acute
      abdominal pain presenting at the emergency department (ED) in two European
      countries. Only adult patients with clinical suspicion of acute appendicitis
      based on medical history, physical examination, and laboratory studies at the
      time of registration in the original cohorts were included in this analysis. WBC
      count and CRP level were determined in all patients and a final diagnosis was
      assigned to every patient by an expert panel based on all available clinical data
      and follow-up. For categories based on symptom duration, the diagnostic accuracy
      of single and combined cutoff values was determined, and negative predictive
      values (NPV) and positive predictive values (PPV) were calculated. Subgroup
      analyses for age (<40 years or >=40 years) and sex were performed. RESULTS: A
      total of 1,024 patients with clinically suspected acute appendicitis were
      included, of whom 580 (57%) were assigned a final diagnosis of appendicitis. No
      value of WBC count, CRP level, or their combination resulted in a NPV of more
      than 90%, regardless of the duration of symptoms. A WBC count of >20 * 10(9) /L
      in combination with symptoms for more than 48 hours was associated with a PPV of
      100%. However, only eight of the 1,024 patients (1%) fulfilled these criteria,
      limiting the clinical applicability. No other cutoff level of WBC count, CRP
      level, or their combination resulted in a PPV of more than 80%, regardless of the
      duration of symptoms. In female patients, normal levels of CRP and WBC count more
      accurately excluded the diagnosis of appendicitis than normal levels did in male
      patients. CONCLUSIONS: No WBC count or CRP level can safely and sufficiently
      confirm or exclude the suspected diagnosis of acute appendicitis in patients who
      present with abdominal pain of 5 days or less in duration.

PMID- 26291310
TI  - Qualitative metasynthesis: a technical exercise or a source of new knowledge?

PMID- 26291311
TI  - KAT5-mediated SOX4 acetylation orchestrates chromatin remodeling during myoblast
      differentiation.
AB  - Transcription factor SOX4 has been implicated in skeletal myoblast
      differentiation through the regulation of Cald1 gene expression; however, the
      detailed molecular mechanism underlying this process is largely unknown. Here, we
      demonstrate that SOX4 acetylation at lysine 95 by KAT5 (also known as Tip60) is
      essential for Cald1 promoter activity at the onset of C2C12 myoblast
      differentiation. KAT5 chromodomain was found to facilitate SOX4 recruitment to
      the Cald1 promoter, which is involved in chromatin remodeling at the promoter.
      Chromatin occupancy analysis of SOX4, KAT5, and HDAC1 indicated that the
      expression of putative SOX4 target genes during C2C12 myoblast differentiation is
      specifically regulated by the molecular switching of the co-activator KAT5 and
      the co-repressor HDAC1 on SOX4 transcriptional activation. 

PMID- 26291312
TI  - A novel lncRNA, LUADT1, promotes lung adenocarcinoma proliferation via the
      epigenetic suppression of p27.
AB  - Long noncoding RNAs (lncRNAs) are known to regulate the development and
      progression of various cancers. However, few lncRNAs have been well characterized
      in lung adenocarcinoma (LUAD). Here, we identified the expression profile of
      lncRNAs and protein-coding genes via microarrays analysis of paired LUAD tissues
      and adjacent non-tumor tissues from five female non-smokes with LUAD. A total of
      498 lncRNAs and 1691 protein-coding genes were differentially expressed between
      LUAD tissues and paired adjacent normal tissues. A novel lncRNA, LUAD transcript
      1 (LUADT1), which is highly expressed in LUAD and correlates with T stage, was
      characterized. Both in vitro and in vivo data showed that LUADT1 knockdown
      significantly inhibited proliferation of LUAD cells and induced cell cycle arrest
      at the G0-G1 phase. Further analysis indicated that LUADT1 may regulate cell
      cycle progression by epigenetically inhibiting the expression of p27. RNA
      immunoprecipitation and chromatin immunoprecipitation assays confirmed that
      LUADT1 binds to SUZ12, a core component of polycomb repressive complex 2, and
      mediates the trimethylation of H3K27 at the promoter region of p27. The negative
      correlation between LUADT1 and p27 expression was confirmed in LUAD tissue
      samples. These data suggested that a set of lncRNAs and protein-coding genes were
      differentially expressed in LUAD. LUADT1 is an oncogenic lncRNA that regulates
      LUAD progression, suggesting that dysregulated lncRNAs may serve as key
      regulatory factors in LUAD progression. 

PMID- 26291313
TI  - Autoregulatory loop between TGF-beta1/miR-411-5p/SPRY4 and MAPK pathway in
      rhabdomyosarcoma modulates proliferation and differentiation.
AB  - The origin of rhabdomyosarcoma (RMS) remains controversial. However, specific
      microRNAs (miRNAs) are downregulated in RMS and it is possible that re-expression
      of these miRNAs may lead to differentiation. Transforming growth factor-beta1
      (TGF-beta1) is known to block differentiation of RMS. We therefore analyzed miRNA
      microarrays of RMS cell lines with or without TGF-beta1 knockdown and identified
      a novel anti-oncogene miR-411-5p. Re-expression of miR-411-5p inhibited RMS cell
      proliferation in vitro and tumorigenicity in vivo. Using a luciferase reporting
      system and sequence analysis, the potential target of miR-411-5p was identified
      as sprouty homolog 4 (SPRY4), which inhibits protein kinase Calpha-mediated
      activation of mitogen-activated protein kinases (MAPKs), especially p38MAPK
      phosphorylation. These results revealed an inverse correlation between TGF
      beta1/SPRY4 and miR-411-5p levels. SPRY4 small interfering RNA and miR-411-5p
      both activated p38MAPK phosphorylation and also promoted apoptosis and myogenic
      differentiation, indicated by increased caspase-3, myosin heavy chain, and myosin
      expression. SPRY4 and miR-411 mRNA levels correlated with TGF-beta1 expression
      levels in RMS tissues, which was confirmed by immunohistochemical staining for
      TGF-beta1, SPRY4, and phosphorylated p38MAPK proteins. Overall, these results
      indicate that miR-411-5p acts as an RMS differentiation-inducing miRNA prompting
      p38MAPK activation via directly downregulating SPRY4. These results establish an
      autoregulatory loop between TGF-beta1/miR-411-5p/SPRY4 and MAPK in RMS, which
      governs the switch between proliferation and differentiation. 

PMID- 26291314
TI  - A rare CYP21A2 mutation in a congenital adrenal hyperplasia kindred displaying
      genotype-phenotype nonconcordance.
AB  - Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency is caused
      by the autosomal recessive inheritance of mutations in the gene CYP21A2. CYP21A2
      mutations lead to variable impairment of the 21-hydroxylase enzyme, which, in
      turn, is associated with three clinical phenotypes, namely, salt wasting, simple
      virilizing, and nonclassical CAH. However, it is known that a given mutation can
      associate with different clinical phenotypes, resulting in a high rate of
      genotype-phenotype nonconcordance. We aimed to study the genotype-phenotype
      nonconcordance in a family with three siblings affected with nonclassical CAH.
      All had hormonal evidence of nonclassical CAH, but this phenotype could not be
      explained by the genotype obtained from commercial CYP21A2 genetic testing, which
      revealed heterozygosity for the maternal 30 kb deletion mutation. We performed
      Sanger sequencing of the entire CYP21A2 gene in this family to search for a rare
      mutation that was not covered by commercial testing and found in the three
      siblings a second, rare c.1097G>A (p.R366H) mutation in exon 8. Computational
      modeling confirmed that this was a mild mutation consistent with nonclassical
      CAH. We recommend that sequencing of entire genes for rare mutations should be
      carried out when genotype-phenotype nonconcordance is observed in patients with
      autosomal recessive monogenic disorders, including CAH.

PMID- 26291315
TI  - Nurse Staffing in Neonatal Intensive Care Units in the United States.
AB  - The neonatal intensive care unit (NICU) is a setting with high nurse-to-patient
      ratios. Little is known about the factors that determine nurse workload and
      assignment. The goals of this study were to (1) develop a measure of NICU infant
      acuity; (2) describe the acuity distribution of NICU infants; (3) describe the
      nurse/infant ratio at each acuity level, and examine the factors other than
      acuity, including nurse qualifications and the availability of physicians and
      other providers, that determined staffing ratios; and (4) explore whether nurse
      qualifications were related to the acuity of assigned infants. In a two-stage
      cohort study, data were collected in 104 NICUs in 2008 by nurse survey (6,038
      nurses and 15,191 infants assigned to them) and administrators reported on unit
      level staffing of non-nurse providers; in a subset of 70 NICUs in 2009-2010,
      census data were collected on four selected shifts (3,871 nurses and 9,276
      infants assigned to them). Most NICU infants (62%) were low-acuity (Levels 1 and
      2); 12% of infants were high-acuity (Levels 4 and 5). The nurse-to-infant ratio
      ranged from 0.33 for the lowest-acuity infants to 0.95 for the highest-acuity
      infants. The staffing ratio was significantly related to the acuity of assigned
      infants but not to nurse education, experience, certification, or availability of
      other providers. There was a significant but small difference in the percentage
      of high-acuity (Levels 4 and 5) infants assigned to nurses with specialty
      certification (15% vs. 12% for nurses without certification). These staffing
      patterns may not optimize patient outcomes in this highly intensive pediatric
      care setting.

PMID- 26291316
TI  - Experimentally Verified Parameter Sets for Modelling Heterogeneous Neocortical
      Pyramidal-Cell Populations.
AB  - Models of neocortical networks are increasingly including the diversity of
      excitatory and inhibitory neuronal classes. Significant variability in cellular
      properties are also seen within a nominal neuronal class and this heterogeneity
      can be expected to influence the population response and information processing
      in networks. Recent studies have examined the population and network effects of
      variability in a particular neuronal parameter with some plausibly chosen
      distribution. However, the empirical variability and covariance seen across
      multiple parameters are rarely included, partly due to the lack of data on
      parameter correlations in forms convenient for model construction. To addess this
      we quantify the heterogeneity within and between the neocortical pyramidal-cell
      classes in layers 2/3, 4, and the slender-tufted and thick-tufted pyramidal cells
      of layer 5 using a combination of intracellular recordings, single-neuron
      modelling and statistical analyses. From the response to both square-pulse and
      naturalistic fluctuating stimuli, we examined the class-dependent variance and
      covariance of electrophysiological parameters and identify the role of the h
      current in generating parameter correlations. A byproduct of the dynamic I-V
      method we employed is the straightforward extraction of reduced neuron models
      from experiment. Empirically these models took the refractory exponential
      integrate-and-fire form and provide an accurate fit to the perisomatic voltage
      responses of the diverse pyramidal-cell populations when the class-dependent
      statistics of the model parameters were respected. By quantifying the parameter
      statistics we obtained an algorithm which generates populations of model neurons,
      for each of the four pyramidal-cell classes, that adhere to experimentally
      observed marginal distributions and parameter correlations. As well as providing
      this tool, which we hope will be of use for exploring the effects of
      heterogeneity in neocortical networks, we also provide the code for the dynamic I
      V method and make the full electrophysiological data set available.

PMID- 26291317
TI  - A new insight into masticatory function and its determinants: a latent class
      analysis.
AB  - OBJECTIVE: Masticatory function is an important factor for preservation of
      general health. Epidemiologic data on masticatory function and its determinants
      among Iranian population are sparse, and no study has evaluated masticatory
      function using latent class analysis (LCA). This study was conducted to
      investigate the masticatory function and its determinants among a large sample of
      Iranian adults. METHODS: In a cross-sectional study among 8691 adults,
      masticatory function was investigated using a validated questionnaire. LCA and
      latent class regression (LCR) were applied to identify classes of masticatory
      function and its potential determinants, respectively. In addition, multigroup
      LCA was conducted based on gender and age categories. RESULTS: In total, 11.24%
      and 24.87% of participants had poor and moderate masticatory function,
      respectively. Males (class size: 14.33%) were more likely to have poor
      masticatory function than females (class size: 2.35%) (P < 0.001). The results of
      LCR showed that higher age [adjusted odds ratio (OR): 1.09, 95% confidence
      interval (95% CI): 1.07-1.11, P < 0.001], male gender (OR: 1.37, 95% CI: 1.01
      1.87, P < 0.05), and low physical activity (OR: 1.41, 95% CI: 1.08-1.85, P <
      0.05) were associated with poor masticatory function. Nonsmokers had a lower
      chance of being in poor masticatory function class than heavy smokers (OR: 0.21,
      95% CI: 0.11-0.38, P < 0.001). CONCLUSION: The prevalence of poor masticatory
      function is high among Iranian adults. Aging, male gender, low levels of physical
      activity, and smoking were found to be associated with poor masticatory function.

PMID- 26291318
TI  - Reference Equation for Respiratory Pressures in Pediatric Population: A
      Multicenter Study.
AB  - Previous studies have proposed only one prediction equation for respiratory
      muscle strength without taking into consideration differences between ages in
      pediatric population. In addition, those researches were single-center studies.
      The objective of this study was to establish reference equations for maximal
      inspiratory pressure (PImax) and maximal expiratory pressure (PEmax) in children
      and teenagers. In a multicenter study, 450 healthy volunteers were evaluated
      (aged 6-18yrs). There were included volunteers with normal lung function. We
      excluded volunteers who could not perform the tests; participated in physical
      activity more than twice a week; were born prematurely; smokers; chronic
      respiratory, cardiologic, and/or neurologic diseases; had acute respiratory
      disease during the prior three weeks. The volunteers were divided into two
      groups: Group 6-11 (6-11yrs) and Group 12-18 (12-18yrs). PImax and PEmax were
      measured according to statement. The mean PImax value was 85.6 (95%IC 83.6-87.6
      cmH2O), and PEmax 84.6 (95%IC 85.5-86.2 cmH2O). The prediction equations for
      PImax and PEmax for Group 6-11 were 37.458-0.559 + (age * 3.253) + (BMI * 0.843)
      + (age * gender * 0.985); and 38.556 + 15.892 + (age * 3.023) + (BMI * 0.579) +
      (age * gender * 0.881), respectively (R2 = 0.34 and 0.31, P<0.001). The equations
      for Group 12-18 were 92.472 + (gender * 9.894) + 7.103, (R2 = 0.27, P = 0.006)
      for PImax; and 68.113 + (gender * 17.022) + 6.46 + (BMI * 0.927), (R2 = 0.34,
      P<0.0001) for PEmax. This multicenter study determined the respiratory muscle
      strength prediction equations for children and teenagers. 

PMID- 26291321
TI  - A lower limb exoskeleton control system based on steady state visual evoked
      potentials.
AB  - OBJECTIVE: We have developed an asynchronous brain-machine interface (BMI)-based
      lower limb exoskeleton control system based on steady-state visual evoked
      potentials (SSVEPs). APPROACH: By decoding electroencephalography signals in real
      time, users are able to walk forward, turn right, turn left, sit, and stand while
      wearing the exoskeleton. SSVEP stimulation is implemented with a visual
      stimulation unit, consisting of five light emitting diodes fixed to the
      exoskeleton. A canonical correlation analysis (CCA) method for the extraction of
      frequency information associated with the SSVEP was used in combination with k
      nearest neighbors. MAIN RESULTS: Overall, 11 healthy subjects participated in the
      experiment to evaluate performance. To achieve the best classification, CCA was
      first calibrated in an offline experiment. In the subsequent online experiment,
      our results exhibit accuracies of 91.3 +/- 5.73%, a response time of 3.28 +/-
      1.82 s, an information transfer rate of 32.9 +/- 9.13 bits/min, and a completion
      time of 1100 +/- 154.92 s for the experimental parcour studied. SIGNIFICANCE: The
      ability to achieve such high quality BMI control indicates that an SSVEP-based
      lower limb exoskeleton for gait assistance is becoming feasible.

PMID- 26291319
TI  - Hepcidin and Host Defense against Infectious Diseases.
AB  - Hepcidin is the master regulator of iron homeostasis in vertebrates. The
      synthesis of hepcidin is induced by systemic iron levels and by inflammatory
      stimuli. While the role of hepcidin in iron regulation is well established, its
      contribution to host defense is emerging as complex and multifaceted. In this
      review, we summarize the literature on the role of hepcidin as a mediator of
      antimicrobial immunity. Hepcidin induction during infection causes depletion of
      extracellular iron, which is thought to be a general defense mechanism against
      many infections by withholding iron from invading pathogens. Conversely, by
      promoting iron sequestration in macrophages, hepcidin may be detrimental to
      cellular defense against certain intracellular infections, although critical in
      vivo studies are needed to confirm this concept. It is not yet clear whether
      hepcidin exerts any iron-independent effects on host defenses. 

PMID- 26291320
TI  - Generation of a Tph2 Conditional Knockout Mouse Line for Time- and Tissue
      Specific Depletion of Brain Serotonin.
AB  - Serotonin has been gaining increasing attention during the last two decades due
      to the dual function of this monoamine as key regulator during critical
      developmental events and as neurotransmitter. Importantly, unbalanced
      serotonergic levels during critical temporal phases might contribute to the onset
      of neuropsychiatric disorders, such as schizophrenia and autism. Despite
      increasing evidences from both animal models and human genetic studies have
      underpinned the importance of serotonin homeostasis maintenance during central
      nervous system development and adulthood, the precise role of this molecule in
      time-specific activities is only beginning to be elucidated. Serotonin synthesis
      is a 2-step process, the first step of which is mediated by the rate-limiting
      activity of Tph enzymes, belonging to the family of aromatic amino acid
      hydroxylases and existing in two isoforms, Tph1 and Tph2, responsible for the
      production of peripheral and brain serotonin, respectively. In the present study,
      we generated and validated a conditional knockout mouse line, Tph2flox/flox, in
      which brain serotonin can be effectively ablated with time specificity. We
      demonstrated that the Cre-mediated excision of the third exon of Tph2 gene
      results in the production of a Tph2null allele in which we observed the near
      complete loss of brain serotonin, as well as the growth defects and perinatal
      lethality observed in serotonin conventional knockouts. We also revealed that in
      mice harbouring the Tph2null allele, but not in wild-types, two distinct Tph2
      mRNA isoforms are present, namely Tph2Delta3 and Tph2Delta3Delta4, with the
      latter showing an in-frame deletion of amino acids 84-178 and coding a protein
      that could potentially retain non-negligible enzymatic activity. As we could not
      detect Tph1 expression in the raphe, we made the hypothesis that the
      Tph2Delta3Delta4 isoform can be at the origin of the residual, sub-threshold
      amount of serotonin detected in the brain of Tph2null/null mice. Finally, we set
      up a tamoxifen administration protocol that allows an efficient, time-specific
      inactivation of brain serotonin synthesis. On the whole, we generated a suitable
      genetic tool to investigate how serotonin depletion impacts on time-specific
      events during central nervous system development and adulthood life. 

PMID- 26291322
TI  - CNV-CH: A Convex Hull Based Segmentation Approach to Detect Copy Number
      Variations (CNV) Using Next-Generation Sequencing Data.
AB  - Copy number variation (CNV) is a form of structural alteration in the mammalian
      DNA sequence, which are associated with many complex neurological diseases as
      well as cancer. The development of next generation sequencing (NGS) technology
      provides us a new dimension towards detection of genomic locations with copy
      number variations. Here we develop an algorithm for detecting CNVs, which is
      based on depth of coverage data generated by NGS technology. In this work, we
      have used a novel way to represent the read count data as a two dimensional
      geometrical point. A key aspect of detecting the regions with CNVs, is to devise
      a proper segmentation algorithm that will distinguish the genomic locations
      having a significant difference in read count data. We have designed a new
      segmentation approach in this context, using convex hull algorithm on the
      geometrical representation of read count data. To our knowledge, most algorithms
      have used a single distribution model of read count data, but here in our
      approach, we have considered the read count data to follow two different
      distribution models independently, which adds to the robustness of detection of
      CNVs. In addition, our algorithm calls CNVs based on the multiple sample analysis
      approach resulting in a low false discovery rate with high precision. 

PMID- 26291323
TI  - Photosynthetic and Growth Response of Sugar Maple (Acer saccharum Marsh.) Mature
      Trees and Seedlings to Calcium, Magnesium, and Nitrogen Additions in the Catskill
      Mountains, NY, USA.
AB  - Decline of sugar maple in North American forests has been attributed to changes
      in soil calcium (Ca) and nitrogen (N) by acidic precipitation. Although N is an
      essential and usually a limiting factor in forests, atmospheric N deposition may
      cause N-saturation leading to loss of soil Ca. Such changes can affect carbon
      gain and growth of sugar maple trees and seedlings. We applied a 22 factorial
      arrangement of N and dolomitic limestone containing Ca and Magnesium (Mg) to 12
      forest plots in the Catskill Mountain region of NY, USA. To quantify the short
      term effects, we measured photosynthetic-light responses of sugar maple mature
      trees and seedlings two or three times during two summers. We estimated maximum
      net photosynthesis (An-max) and its related light intensity (PAR at An-max),
      apparent quantum efficiency (Aqe), and light compensation point (LCP). To
      quantify the long-term effects, we measured basal area of living mature trees
      before and 4 and 8 years after treatment applications. Soil and foliar chemistry
      variables were also measured. Dolomitic limestone increased Ca, Mg, and pH in the
      soil Oe horizon. Mg was increased in the B horizon when comparing the plots
      receiving N with those receiving CaMg. In mature trees, foliar Ca and Mg
      concentrations were higher in the CaMg and N+CaMg plots than in the reference or
      N plots; foliar Ca concentration was higher in the N+CaMg plots compared with the
      CaMg plots, foliar Mg was higher in the CaMg plots than the N+CaMg plots; An-max
      was maximized due to N+CaMg treatment; Aqe decreased by N addition; and PAR at An
      max increased by N or CaMg treatments alone, but the increase was maximized by
      their combination. No treatment effect was detected on basal areas of living
      mature trees four or eight years after treatment applications. In seedlings, An
      max was increased by N+CaMg addition. The reference plots had an open herbaceous
      layer, but the plots receiving N had a dense monoculture of common woodfern in
      the forest floor, which can impede seedling survival. 

PMID- 26291324
TI  - Experience Drives Synchronization: The phase and Amplitude Dynamics of Neural
      Oscillations to Musical Chords Are Differentially Modulated by Musical Expertise.
AB  - Musical expertise is associated with structural and functional changes in the
      brain that underlie facilitated auditory perception. We investigated whether the
      phase locking (PL) and amplitude modulations (AM) of neuronal oscillations in
      response to musical chords are correlated with musical expertise and whether they
      reflect the prototypicality of chords in Western tonal music. To this aim, we
      recorded magnetoencephalography (MEG) while musicians and non-musicians were
      presented with common prototypical major and minor chords, and with uncommon, non
      prototypical dissonant and mistuned chords, while watching a silenced movie. We
      then analyzed the PL and AM of ongoing oscillations in the theta (4-8 Hz) alpha
      (8-14 Hz), beta- (14-30 Hz) and gamma- (30-80 Hz) bands to these chords. We found
      that musical expertise was associated with strengthened PL of ongoing
      oscillations to chords over a wide frequency range during the first 300 ms from
      stimulus onset, as opposed to increased alpha-band AM to chords over temporal MEG
      channels. In musicians, the gamma-band PL was strongest to non-prototypical
      compared to other chords, while in non-musicians PL was strongest to minor
      chords. In both musicians and non-musicians the long-latency (> 200 ms) gamma
      band PL was also sensitive to chord identity, and particularly to the amplitude
      modulations (beats) of the dissonant chord. These findings suggest that musical
      expertise modulates oscillation PL to musical chords and that the strength of
      these modulations is dependent on chord prototypicality. 

PMID- 26291325
TI  - Metformin Induces Apoptosis and Downregulates Pyruvate Kinase M2 in Breast Cancer
      Cells Only When Grown in Nutrient-Poor Conditions.
AB  - INTRODUCTION: Metformin is proposed as adjuvant therapy in cancer treatment
      because of its ability to limit cancer incidence by negatively modulating the
      PI3K/AKT/mTOR pathway. In vitro, in addition to inhibiting cancer cell
      proliferation, metformin can also induce apoptosis. The molecular mechanism
      underlying this second effect is still poorly characterized and published data
      are often contrasting. We investigated how nutrient availability can modulate
      metformin-induced apoptosis in three breast cancer cell lines. MATERIAL AND
      METHODS: MCF7, SKBR3 and MDA-MB-231 cells were plated in MEM medium supplemented
      with increasing glucose concentrations or in DMEM medium and treated with 10 mM
      metformin. Cell viability was monitored by Trypan Blue assay and treatment
      effects on Akt/mTOR pathway and on apoptosis were analysed by Western Blot.
      Moreover, we determined the level of expression of pyruvate kinase M2 (PKM2), a
      well-known glycolytic enzyme expressed in cancer cells. RESULTS: Our results
      showed that metformin can induce apoptosis in breast cancer cells when cultured
      at physiological glucose concentrations and that the pro-apoptotic effect was
      completely abolished when cells were grown in high glucose/high amino acid
      medium. Induction of apoptosis was found to be dependent on AMPK activation but,
      at least partially, independent of TORC1 inactivation. Finally, we showed that,
      in nutrient-poor conditions, metformin was able to modulate the intracellular
      glycolytic equilibrium by downregulating PKM2 expression and that this mechanism
      was mediated by AMPK activation. CONCLUSION: We demonstrated that metformin
      induces breast cancer cell apoptosis and PKM2 downregulation only in nutrient
      poor conditions. Not only glucose levels but also amino acid concentration can
      influence the observed metformin inhibitory effect on the mTOR pathway as well as
      its pro-apoptotic effect. These data demonstrate that the reduction of nutrient
      supply in tumors can increase metformin efficacy and that modulation of PKM2
      expression/activity could be a promising strategy to boost metformin anti-cancer
      effect.

PMID- 26291326
TI  - Recovery of Physiological Traits in Saplings of Invasive Bischofia Tree Compared
      with Three Species Native to the Bonin Islands under Successive Drought and
      Irrigation Cycles.
AB  - Partial leaf shedding induced by hydraulic failure under prolonged drought can
      prevent excess water consumption, resulting in delayed recovery of carbon
      productivity following rainfall. To understand the manner of water use of
      invasive species in oceanic island forests under a fluctuating water regime, leaf
      shedding, multiple physiological traits, and the progress of embolism in the stem
      xylem under repeated drought-irrigation cycles were examined in the potted
      saplings of an invasive species, Bischofia javanica Blume, and three endemic
      native species, Schima mertensiana (Sieb. Et Zucc,) Koitz., Hibiscus glaber
      Matsum, and Distylium lepidotum Nakai, from the Bonin Islands, Japan. The
      progress of xylem embolism was observed by cryo-scanning electron microscopy. The
      samples exhibited different processes of water saving and drought tolerance based
      on the different combinations of partial leaf shedding involved in embolized
      conduits following repeated de-rehydration. Predawn leaf water potential largely
      decreased with each successive drought-irrigation cycle for all tree species,
      except for B. javanica. B. javanica shed leaves conspicuously under drought and
      showed responsive stomatal conductance to VPD, which contributed to recover leaf
      gas exchange in the remaining leaves, following a restored water supply. In
      contrast, native tree species did not completely recover photosynthetic rates
      during the repeated drought-irrigation cycles. H. glaber and D. lepidotum
      preserved water in vessels and adjusted leaf osmotic rates but did not actively
      shed leaves. S. mertensiana exhibited partial leaf shedding during the first
      cycle with an osmotic adjustment, but they showed less responsive stomatal
      conductance to VPD. Our data indicate that invasive B. javanica saplings can
      effectively use water supplied suddenly under drought conditions. We predict that
      fluctuating precipitation in the future may change tree distributions even in
      mesic or moist sites in the Bonin Islands. 

PMID- 26291328
TI  - Context-Dependent Plastic Response during Egg-Laying in a Widespread Newt
      Species.
AB  - Previous research on predator-induced phenotypic plasticity mostly focused on
      responses in morphology, developmental time and/or behaviour during early life
      stages, but the potential significance of anticipatory parental responses has
      been investigated less often. In this study I examined behavioural and maternal
      responses of gravid female smooth newts, Lissotriton vulgaris, in the presence of
      chemical cues originating from invertebrate predators, Acilius sulcatus water
      beetles and Aeshna cyanea dragonfly larvae. More specifically, I tested the
      extent of oviposition preference, plasticity in egg-wrapping behaviour and
      plasticity in egg size when females had the possibility to lay eggs at
      oviposition sites with and without predator cues during overnight trials. I found
      that individuals did not avoid laying eggs in the environment with predator cues;
      however, individuals that deposited eggs into both environments adjusted the size
      of the laid eggs to the perceived environment. Females deposited larger eggs
      earlier in the season but egg size decreased with time in the absence of predator
      cues, whereas individuals laid eggs of average size throughout the investigated
      reproductive period when such cues were present. Also, egg size was found to be
      positively related to hatching success. Individuals did not adjust their wrapping
      behaviour to the presence of predator cues, but females differed in the extent of
      egg-wrapping between ponds. Females' body mass and tail depth were also different
      between ponds, whereas their body size was positively associated with egg size.
      According to these results, female smooth newts have the potential to exhibit
      activational plasticity and invest differently into eggs depending on temporal
      and environmental factors. Such an anticipatory response may contribute to the
      success of this caudate species under a wide range of predator regimes at its
      natural breeding habitats. 

PMID- 26291329
TI  - Multi-lineage differentiation and angiogenesis potentials of pigmented
      villonodular synovitis derived mesenchymal stem cells--pathological implication.
AB  - Pigmented villonodular synovitis (PVNS) is a benign tissue proliferation
      characterized by its hyper-vascularity within the lesion. The true etiology and
      cell source of this disease entity still remain unclear. Mesenchymal stem cells
      (MSCs) exist in various tissues of human body. However, it has not been clarified
      whether MSCs could be isolated from tissue of PVNS. Here, we isolated MSCs from
      PVNS (PVNS-SCs), and by comparing to the MSCs from normal synovium (Syn-SCs) of
      the same individual, we investigated whether PVNS-SCs differed in the capacity
      for multi-differentiation and inducing angiogenesis. We first demonstrated that
      PVNS-SCs existed in the lesion of PVNS of three individuals. Moreover, we showed
      PVNS-SCs had better osteogenic differentiation potential than Syn-SCs, whereas
      Syn-SCs had better capacity for adipogenic and chondrogenic differentiation. By
      genome-wide analysis of gene expression profile using a complementary DNA
      microarray and comparing to Syn-SCs, we identified in PVNS-SCs a distinct gene
      expression profile characterized by up-regulation of genes involved in
      angiogenesis. In vitro and in vivo studies further confirmed that PVNS-SCs had
      better capacities for promoting angiogenesis. In summary, the identification of
      PVNS-SCs in PVNS tissue and their distinct angiogenic potential may help
      elucidate the underlying etiology of this disease.

PMID- 26291327
TI  - Evolution and Design Governing Signal Precision and Amplification in a Bacterial
      Chemosensory Pathway.
AB  - Understanding the principles underlying the plasticity of signal transduction
      networks is fundamental to decipher the functioning of living cells. In
      Myxococcus xanthus, a particular chemosensory system (Frz) coordinates the
      activity of two separate motility systems (the A- and S-motility systems),
      promoting multicellular development. This unusual structure asks how signal is
      transduced in a branched signal transduction pathway. Using combined evolution
      guided and single cell approaches, we successfully uncoupled the regulations and
      showed that the A-motility regulation system branched-off an existing signaling
      system that initially only controlled S-motility. Pathway branching emerged in
      part following a gene duplication event and changes in the circuit structure
      increasing the signaling efficiency. In the evolved pathway, the Frz histidine
      kinase generates a steep biphasic response to increasing external stimulations,
      which is essential for signal partitioning to the motility systems. We further
      show that this behavior results from the action of two accessory response
      regulator proteins that act independently to filter and amplify signals from the
      upstream kinase. Thus, signal amplification loops may underlie the emergence of
      new connectivity in signal transduction pathways. 

PMID- 26291330
TI  - The effect of combined hormonal contraceptives use on brain reactivity during
      response inhibition.
AB  - OBJECTIVES: Cognitive control, which can be described as the ability to moderate
      impulses, has not previously been investigated in users of combined hormonal
      contraception (CHC). Given the suggested modulatory role of ovarian steroids in
      prefrontal dopaminergic function, which in turn taps into cognitive control, this
      randomised, double-blinded, placebo-controlled oral contraceptive trial set out
      to investigate the brain activity pattern during response inhibition in CHC
      users. METHODS: Thirty-four women were randomised to one treatment cycle with a
      levonorgestrel-containing CHC or placebo. The women performed a Go/NoGo task to
      measure brain activity during response inhibition by use of event-related
      functional magnetic resonance imaging (fMRI) prior to and during the CHC/placebo
      treatment cycle. RESULTS: No differences between CHC and placebo users in number
      of correct inhibitions were found during treatment, but only women on CHC
      significantly improved their performance between the baseline and treatment
      assessments. During the treatment cycle CHC users displayed decreased activity in
      the right middle frontal gyrus in comparison with placebo users. No other
      significant activations were evident between treatment groups or within groups.
      CONCLUSION: Overall, CHC use had marginal effects on brain activity during
      response inhibition. If anything, the findings of the study may suggest reduced
      effort or increased efficiency in maintaining orbitofrontal cortex inhibitory
      cognitive control when using a combined oral contraceptive.

PMID- 26291331
TI  - Orange Zinc Germanate with Metallic Ge-Ge Bonds as a Chromophore-Like Center for
      Visible-Light-Driven Water Splitting.
AB  - The efficiency of solar-energy-conversion devices depends on the absorption
      region and intensity of the photon collectors. Organic chromophores, which have
      been widely stabilized on inorganic semiconductors for light trapping, are
      limited by the interface between the chromophore and semiconductor. Herein we
      report a novel orange zinc germanate (Zn-Ge-O) with a chromophore-like structure,
      by which the absorption region can be dramatically expanded. Structural
      characterizations and theoretical calculations together reveal that the origin of
      visible-light response can be attributed to the unusual metallic Ge-Ge bonds
      which act in a similar way to organic chromophores. Benefiting from the enhanced
      light harvest, the orange Zn-Ge-O demonstrates superior capacity for solar-driven
      hydrogen production.

PMID- 26291332
TI  - Zintl-phase Sr3LiAs2H: crystal structure and chemical bonding analysis by the
      electron localizability approach.
AB  - The compound Sr3 LiAs2 H was synthesized by reaction of elemental strontium,
      lithium, and arsenic, as well as LiH as hydrogen source. The crystal structure
      was determined by single-crystal X-ray diffraction: space group Pnma; Pearson
      symbol oP28; a = 12.0340(7), b = 4.4698(2), c = 12.5907(5) A; V = 677.2(1) A(3) ;
      RF  = 0.047 for 1021 reflections and with 36 parameters refined. The positions of
      the hydrogen atoms were first revealed by the electron localizability indicator
      and subsequently confirmed by crystal structure refinement. In the crystal
      structure of Sr3 LiAs2 H the metal atoms are arranged in a Gd3 NiSi2 -type motif,
      whereas the hydrogen atoms are arranged in a distorted tetrahedral environment
      formed by strontium. The calculated band structure revealed that Sr3 LiAs2 H is a
      semiconductor, which is in agreement with its diamagnetic behavior. Thus, Sr3
      LiAs2 H is considered as a (charge-balanced) Zintl phase. 

PMID- 26291333
TI  - A New Class of Safe, Potent, and Specific P-gp Modulator: Flavonoid Dimer FD18
      Reverses P-gp-Mediated Multidrug Resistance in Human Breast Xenograft in Vivo.
AB  - Flavonoid dimer FD18 is a new class of dimeric P-gp modulator that can reverse
      cancer drug resistance. FD18 is a potent (EC50 = 148 nM for paclitaxel), safe
      (selective index = 574), and selective P-glycoprotein (P-gp) modulator. FD18 can
      modulate multidrug resistance toward paclitaxel, vinblastine, vincristine,
      doxorubicin, daunorubicin, and mitoxantrone in human breast cancer LCC6MDR in
      vitro. FD18 (1 MUM) can revert chemosensitivity of LCC6MDR back to parental LCC6
      level. FD18 was 11- to 46-fold more potent than verapamil. FD18 (1 MUM) can
      increase accumulation of doxorubicin by 2.7-fold, daunorubicin (2.1-fold), and
      rhodamine 123 (5.2-fold) in LCC6MDR. FD18 inhibited P-gp-mediated doxorubicin
      efflux and has no effect on influx. FD18 at 1 MUM did not affect the protein
      expression level of P-gp. Pharmacokinetics studies indicated that intraperitoneal
      administration of 45 mg/kg FD18 was enough to maintain a plasma level above EC50
      (148 nM) for more than 600 min. Toxicity studies with FD18 (90 mg/kg, i.p. for 12
      times in 22 days) with paclitaxel (12 mg/kg, i.v. for 12 times in 22 days)
      revealed no obvious toxicity or death in mice. In vivo efficacy studies indicated
      that FD18 (45 mg/kg, i.p. for 12 times in 22 days) together with paclitaxel (12
      mg/kg, i.v. for 12 times in 22 days) resulted in a 46% reduction in LCC6MDR
      xenograft volume (n = 11; 648 +/- 84 mm(3)) compared to paclitaxel control (n =
      8; 1201 +/- 118 mm(3)). There were no animal deaths or significant drop in body
      weight and vital organ wet weight. FD18 can increase paclitaxel accumulation in
      LCC6MDR xenograft by 1.8- to 2.2-fold. The present study suggests that FD18
      represents a new class of safe and potent P-gp modulator in vivo. 

PMID- 26291334
TI  - Brugada Syndrome Phenotype Elimination by Epicardial Substrate Ablation.
AB  - BACKGROUND: Whether Brugada syndrome (BrS) depends on functional epicardial
      substrates, which may be definitively eliminated by radiofrequency ablation,
      remains unknown. METHODS AND RESULTS: Patients with BrS underwent epicardial
      mapping to identify areas of abnormal electrograms as target for radiofrequency
      ablation. Substrate identification consisted in mapping right ventricle
      epicardial surface before and after flecainide (2 mg/kg per 10 minutes). After
      radiofrequency ablation, flecainide and remap confirmed elimination of abnormal
      substrate, BrS ECG pattern, and ventricular tachycardia/ventricular fibrillation
      inducibility. Flecainide testing was performed at each follow-up visits <=6
      months. Fourteen patients with BrS, median age 39 years (30.3-42.3) with
      implantable cardioverter-defibrillator were enrolled. Low-voltage areas (<1.5 mV)
      were commonly identified on the anterior right free wall and right ventricular
      outflow tract, which increased after flecainide from 17.6 cm(2) (12.1-24.2) to
      28.5 cm(2) (21.6-30.2; P=0.001). Similarly, areas with abnormal electrograms
      increased after flecainide from 19.0 (17.5-23.6) to 27.3 cm(2) (24.0-31.2;
      P=0.001). After 23.8 minutes (18.1-28.5) of radiofrequency ablation, abnormal
      electrograms disappeared, whereas low-voltage areas were replaced by scar areas
      (<0.5 mV) of 25.9 cm(2) (19.6-31.0). Substrate elimination resulted in BrS ECG
      pattern disappearance and no ventricular tachycardia/ventricular fibrillation
      inducibility without complications. After a median follow-up of 5 months (3.8
      5.3), ECG remained normal despite flecainide. CONCLUSIONS: In patients with BrS,
      there is a relationship between abnormal ECG pattern, the extent of abnormal
      epicardial substrate, and ventricular tachycardia/ventricular fibrillation
      inducibility. Ablation of the substrate identified in the presence of flecainide
      can eliminate the BrS phenotype and warrants further study.

PMID- 26291335
TI  - Vilazodone in patients with generalized anxiety disorder: a double-blind,
      randomized, placebo-controlled, flexible-dose study.
AB  - Vilazodone is a selective serotonin reuptake inhibitor and a 5-HT1A receptor
      partial agonist that is approved for treatment of major depressive disorder in
      adults in the USA and Mexico. The efficacy, safety, and tolerability of
      vilazodone for generalized anxiety disorder (GAD) were investigated in a clinical
      trial (NCT01766401 ClinicalTrials.gov). Participants (18-70 years, inclusive) who
      met Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text
      revision, criteria for GAD were randomized (1:1) to placebo or flexible-dose
      vilazodone (20-40 mg/day) for 8 weeks of double-blind treatment. Primary and
      secondary efficacy parameters were changes from baseline to week 8 in Hamilton
      Rating Scale for Anxiety and Sheehan Disability Scale total scores, respectively.
      Analysis was based on a mixed-effects model for repeated measures approach on the
      intent-to-treat population. The intent-to-treat population comprised 395 patients
      (placebo=197, vilazodone=198); 77% completed the study. The least squares mean
      difference in change from baseline to week 8 in the Hamilton Rating Scale for
      Anxiety total score was statistically significant for vilazodone versus placebo [
      1.50 (-2.96, -0.04), P=0.0438]. The mean change from baseline to week 8 in the
      Sheehan Disability Scale total score for vilazodone versus placebo was not
      statistically significant. Adverse events were reported in 60% of placebo-treated
      and 83% of vilazodone-treated patients. This was a positive clinical trial of 20
      40 mg/day vilazodone versus placebo in the treatment of GAD.

PMID- 26291336
TI  - Enhancing Lyme Disease Surveillance by Using Administrative Claims Data,
      Tennessee, USA.
AB  - Lyme disease is underreported in the United States. We used insurance
      administrative claims data to determine the value of such data in enhancing case
      ascertainment in Tennessee during January 2011-June 2013. Although we identified
      ~20% more cases of Lyme disease (5/year), the method was resource intensive and
      not sustainable in this low-incidence state. 

PMID- 26291337
TI  - Attenuation of miR-17~92 Cluster in Bronchopulmonary Dysplasia.
AB  - RATIONALE: Bronchopulmonary dysplasia remains a significant cause of neonatal
      morbidity; however, the identification of novel targets to predict or prevent the
      development of bronchopulmonary dysplasia remains elusive. Proper microRNA (miR)
      17~92 cluster is necessary for normal lung development, and alterations in
      expression are reported in other pulmonary diseases. The overall hypothesis for
      our work is that altered miR-17~92 cluster expression contributes to the
      molecular pathogenesis of bronchopulmonary dysplasia. OBJECTIVES: The current
      studies tested the hypothesis that alterations in miR-17~92 cluster and DNA
      methyltransferase expression are present in bronchopulmonary dysplasia. METHODS:
      miR-17~92 cluster expression, promoter methylation, and DNA methyltransferase
      expression were determined in autopsy lung samples obtained from premature
      infants who died with bronchopulmonary dysplasia, or from term/near-term infants
      who died from nonrespiratory causes. Expression of miR-17~92 cluster members miR
      17 and -19b was measured in plasma samples collected in the first week of life
      from a separate cohort of preterm infants at a second institution in whom
      bronchopulmonary dysplasia was diagnosed subsequently. MEASUREMENTS AND MAIN
      RESULTS: Autopsy tissue data indicated that miR-17~92 expression is significantly
      lower in bronchopulmonary dysplasia lungs and is inversely correlated with
      promoter methylation and DNA methyltransferase expression when compared with that
      of control subjects without bronchopulmonary dysplasia. Plasma sample analyses
      indicated that miR-17 and -19b expression was decreased in infants who
      subsequently developed bronchopulmonary dysplasia. CONCLUSIONS: Our data are the
      first to demonstrate altered expression of the miR-17~92 cluster in
      bronchopulmonary dysplasia. The consistency between our autopsy and plasma
      findings further support our working hypothesis that the miR-17~92 cluster
      contributes to the molecular pathogenesis of bronchopulmonary dysplasia.

PMID- 26291339
TI  - Prediction of the optimal set of contacts to fold the smallest knotted protein.
AB  - Knotted protein chains represent a new motif in protein folds. They have been
      linked to various diseases, and recent extensive analysis of the Protein Data
      Bank shows that they constitute 1.5% of all deposited protein structures. Despite
      thorough theoretical and experimental investigations, the role of knots in
      proteins still remains elusive. Nonetheless, it is believed that knots play an
      important role in mechanical and thermal stability of proteins. Here, we perform
      a comprehensive analysis of native, shadow-specific and non-native interactions
      which describe free energy landscape of the smallest knotted protein (PDB id
      2efv). We show that the addition of shadow-specific contacts in the loop region
      greatly enhances folding kinetics, while the addition of shadow-specific contacts
      along the C-terminal region (H3 or H4) results in a new folding route with slower
      kinetics. By means of direct coupling analysis (DCA) we predict non-native
      contacts which also can accelerate kinetics. Next, we show that the length of the
      C-terminal knot tail is responsible for the shape of the free energy barrier,
      while the influence of the elongation of the N-terminus is not significant.
      Finally, we develop a concept of a minimal contact map sufficient for 2efv
      protein to fold and analyze properties of this protein using this map. 

PMID- 26291340
TI  - Contact Freezing of Water by Salts.
AB  - Water is unlikely to crystallize homogeneously at temperatures greater than -34 
      degrees C. Freezing at higher temperatures is heterogeneous-catalyzed by the
      presence of a second substance. If that substance is at an air-water interface,
      then the mode is called contact freezing, and it typically will trigger
      nucleation at a higher temperature than if the substance were wholly immersed
      within the liquid. We find that the impact of salt particles initiates freezing
      in experiments using water droplets at supercoolings of 9 to 16  degrees C. These
      results show that contact freezing nuclei need not be effective as immersion mode
      nuclei. We discuss our results in the context of proposed mechanisms of contact
      freezing. Finally, we use the time scales for diffusion of heat and of ions and
      the propagation of a sound wave through the droplet to estimate that contact
      freezing occurs within 10 ns of impact. 

PMID- 26291341
TI  - Identification and Optimization of Benzimidazole Sulfonamides as Orally
      Bioavailable Sphingosine 1-Phosphate Receptor 1 Antagonists with in Vivo
      Activity.
AB  - We report here a novel series of benzimidazole sulfonamides that act as
      antagonists of the S1P1 receptor, identified by exploiting an understanding of
      the pharmacophore of a high throughput screening (HTS)-derived series of
      compounds described previously. Lead compound 2 potently inhibits S1P-induced
      receptor internalization in a cell-based assay (EC50 = 0.05 MUM), but has poor
      physical properties and metabolic stability. Evolution of this compound through
      structure-activity relationship development and property optimization led to in
      vivo probes such as 4. However, this compound was unexpectedly found to be a
      potent CYP3A inducer in human hepatocytes, and thus further chemistry efforts
      were directed at addressing this liability. By employing a pregnane X receptor
      (PXR) reporter gene assay to prioritize compounds for further testing in human
      hepatocytes, we identified lipophilicity as a key molecular property influencing
      the likelihood of P450 induction. Ultimately, we have identified compounds such
      as 46 and 47, which demonstrate the desired S1P1 antagonist activity while having
      greatly reduced risk of CYP3A induction in humans. These compounds have excellent
      oral bioavailability in preclinical species and exhibit pharmacodynamic effects
      of S1P1 antagonism in several in vivo models following oral dosing. Relatively
      modest antitumor activity was observed in multiple xenograft models, however,
      suggesting that selective S1P1 antagonists would have limited utility as
      anticancer therapeutics as single agents. 

PMID- 26291343
TI  - Synthesis of Isoquinolones Using Visible-Light-Promoted Denitrogenative Alkyne
      Insertion of 1,2,3-Benzotriazinones.
AB  - A visible-light-promoted regioselective denitrogenative insertion of terminal
      alkynes into 1,2,3-benzotriazinones is reported. This mechanistically novel
      process allows the synthesis of substituted isoquinolones in satisfactory
      isolated yields (24 examples, 46-84% yield) at room temperature under visible
      light irradiation with the assistance of a photocatalyst. The proposed single
      electron-transfer pathway was supported by TEMPO trapping, radical clock
      experiments, and Stern-Volmer analysis. 

PMID- 26291342
TI  - Quantum dots based potential-resolution dual-targets electrochemiluminescent
      immunosensor for subtype of tumor marker and its serological evaluation.
AB  - The identification of subtypes of known tumor markers is of great importance for
      clinical diagnosis but still a great challenge in novel detection methodologies
      with simple operation and acceptable sensitivity. This work for the first time
      reported a quantum dots (QDs) based potential-resolved electrochemiluminescent
      (ECL) immunosensor to realize simultaneous detection of dual targets. Because of
      different surface microstructures, dimercaptosuccinic acid stabilized CdTe (DMSA
      CdTe) QDs and TiO2 nanoparticles-glutathione stabilized CdTe (TiO2-GSH-CdTe) QDs
      composites showed a large difference of ECL peak potential (~360 mV), which
      provided an access for potential-resolution detection. The ECL emission on indium
      tin oxide electrodes showed consistent strength during the cyclic scan, and
      intensity data were collected at -0.89 V and -1.25 V (vs Ag/AgCl) for DMSA-CdTe
      QDs and TiO2-GSH-CdTe QDs composites, respectively. The interface modification
      procedures of immunosensor construction were characterized by atomic force
      microscopy. The portion of Lens culinaris lectin affiliated isoform of alpha
      fetoprotein (AFP), AFP-L3%, in total AFP, is recently a novel criteria showing
      even higher sensitivity and specificity than AFP at the early stage of cancer.
      Combined with the enzyme cyclic amplification strategy, linear ranges for AFP-L3
      and AFP dual-targets detection were 3.24 pg mL(-1)-32.4 ng mL(-1) and 1.0 pg mL(
      1)-20 ng mL(-1), with limits of detection of 3.24 pg mL(-1) and 1.0 pg mL(-1),
      respectively. Compared with clinical detection data, the calculated portion of
      AFP-L3% by as-prepared immunosensor showed acceptable accuracy. These results
      open a new avenue for facile and rapid multiple-components detection based on the
      nano-ECL technique and provide a new clinical diagnosis platform for HCC. 

PMID- 26291338
TI  - Randomized Controlled Trial of Minimally Invasive Sacroiliac Joint Fusion Using
      Triangular Titanium Implants vs Nonsurgical Management for Sacroiliac Joint
      Dysfunction: 12-Month Outcomes.
AB  - BACKGROUND: Sacroiliac joint (SIJ) dysfunction is a prevalent cause of chronic,
      unremitting lower back pain. OBJECTIVE: To concurrently compare outcomes after
      surgical and nonsurgical treatment for chronic SIJ dysfunction. METHODS: A total
      of 148 subjects with SIJ dysfunction were randomly assigned to minimally invasive
      SIJ fusion with triangular titanium implants (n = 102) or nonsurgical management
      (n = 46). Pain, disability, and quality-of-life scores were collected at baseline
      and at 1, 3, 6, and 12 months. Success rates were compared using Bayesian
      methods. Crossover from nonsurgical to surgical care was allowed after the 6
      month study visit was complete. RESULTS: Six-month success rates were higher in
      the surgical group (81.4% vs 26.1%; posterior probability of superiority >
      0.9999). Clinically important (>= 15 point) Oswestry Disability Index improvement
      at 6 months occurred in 73.3% of the SIJ fusion group vs 13.6% of the nonsurgical
      management group (P < .001). At 12 months, improvements in SIJ pain and Oswestry
      Disability Index were sustained in the surgical group. Subjects who crossed over
      had improvements in pain, disability, and quality of life similar to those in the
      original surgical group. Adverse events were slightly more common in the surgical
      group (1.3 vs 1.1 events per subject; P = .31). CONCLUSION: This Level 1 study
      showed that minimally invasive SIJ fusion using triangular titanium implants was
      more effective than nonsurgical management at 1 year in relieving pain, improving
      function, and improving quality of life in patients with SIJ dysfunction caused
      by degenerative sacroiliitis or SIJ disruptions. Pain, disability, and quality of
      life also improved after crossover from nonsurgical to surgical treatment.

PMID- 26291344
TI  - Morphological Transformations in Solid Domains of Alkanes on Surfactant
      Solutions.
AB  - Alkanes on surfactant solutions can form three distinct phases at the air
      solution interface, a liquid phase (L), a solid monolayer phase (S1), and a
      hybrid bilayer phase (S2). Phase coexistence between any two, or all three, of
      these phases has been observed by Brewster angle microscopy of tetradecane,
      hexadecane, and their mixtures on solutions of tetradecyltrimethylammonium
      bromide. The morphologies of the domains depend on the competition between line
      tension and electrostatic interactions, which are essentially different depending
      on the pair of phases in contact. Domains of S1 in the L phase are long and thin;
      however, long, thin domains of L in an S1 phase are not stable but break up into
      a string of small circular domains. The bilayer S2 domains are always circular,
      owing to the dominance of line tension on the morphology. 

PMID- 26291345
TI  - Existence of a Correlation Bound s-Type Anion State of C60.
AB  - It is established using high-level electronic structure calculations that C60 has
      an s-type correlation-bound anion state with an electron binding energy of about
      120 meV. Examination of the "singly occupied" natural orbital of the anion
      reveals that about 9% of the charge density of the excess electron is localized
      inside, and about 91% is localized outside the C60 cage. Calculations were also
      carried out for the He@C60, Ne@C60, and H2O@C60 endohedral complexes. For each of
      these species, the s-type anion is predicted to be less strongly bound than for
      C60 itself. 

PMID- 26291346
TI  - Photoswitchable Molecular Rings for Solar-Thermal Energy Storage.
AB  - Solar-thermal fuels reversibly store solar energy in the chemical bonds of
      molecules by photoconversion, and can release this stored energy in the form of
      heat upon activation. Many conventional photoswichable molecules could be
      considered as solar thermal fuels, although they suffer from low energy density
      or short lifetime in the photoinduced high-energy metastable state, rendering
      their practical use unfeasible. We present a new approach to the design of
      chemistries for solar thermal fuel applications, wherein well-known
      photoswitchable molecules are connected by different linker agents to form
      molecular rings. This approach allows for a significant increase in both the
      amount of stored energy per molecule and the stability of the fuels. Our results
      suggest a range of possibilities for tuning the energy density and thermal
      stability as a function of the type of the photoswitchable molecule, the ring
      size, or the type of linkers. 

PMID- 26291347
TI  - Why Cells are Microscopic: A Transport-Time Perspective.
AB  - Physical-chemical reasoning is used to demonstrate that the sizes of both
      prokaryotic and eukaryotic cells are such that they minimize the times needed for
      the macromolecules to migrate throughout the cells and interact/react with one
      another. This conclusion does not depend on a particular form of the crowded
      medium diffusion model, as thus points toward a potential optimization principle
      of cellular organisms. In eukaryotes, size optimality renders the diffusive
      transport as efficient as active transport - in this way, the cells can conserve
      energetic resources that would otherwise be expended in active transport. 

PMID- 26291348
TI  - Epitaxial Cubic Ce2O3 Films via Ce-CeO2 Interfacial Reaction.
AB  - Thin films of reduced ceria supported on metals are often applied as substrates
      in model studies of the chemical reactivity of ceria based catalysts. Of special
      interest are the properties of oxygen vacancies in ceria. However, thin films of
      ceria prepared by established methods become increasingly disordered as the
      concentration of vacancies increases. Here, we propose an alternative method for
      preparing ordered reduced ceria films based on the physical vapor deposition and
      interfacial reaction of Ce with CeO2 films. The method yields bulk-truncated
      layers of cubic c-Ce2O3. Compared to CeO2 these layers contain 25% of perfectly
      ordered vacancies in the surface and subsurface allowing well-defined
      measurements of the properties of ceria in the limit of extreme reduction.
      Experimentally, c-Ce2O3(111) layers are easily identified by a characteristic 4 *
      4 surface reconstruction with respect to CeO2(111). In addition, c-Ce2O3 layers
      represent an experimental realization of a normally unstable polymorph of Ce2O3.
      During interfacial reaction, c-Ce2O3 nucleates on the interface between CeO2
      buffer and Ce overlayer and is further stabilized most likely by the tetragonal
      distortion of the ceria layers on Cu. The characteristic kinetics of the metal
      oxide interfacial reactions may represent a vehicle for making other metastable
      oxide structures experimentally available. 

PMID- 26291349
TI  - Direct In Situ Quantification of HO2 from a Flow Reactor.
AB  - The first direct in situ measurements of hydroperoxyl radical (HO2) at
      atmospheric pressure from the exit of a laminar flow reactor have been carried
      out using mid-infrared Faraday rotation spectroscopy. HO2 was generated by
      oxidation of dimethyl ether, a potential renewable biofuel with a simple
      molecular structure but rich low-temperature oxidation chemistry. On the basis of
      the results of nonlinear fitting of the experimental data to a theoretical
      spectroscopic model, the technique offers an estimated sensitivity of <1 ppmv
      over a reactor exit temperature range of 398-673 K. Accurate in situ measurement
      of this species will aid in quantitative modeling of low-temperature and high
      pressure combustion kinetics. 

PMID- 26291350
TI  - Elucidating Operating Modes of Bulk-Heterojunction Solar Cells from Impedance
      Spectroscopy Analysis.
AB  - We discuss the progress and challenges in the application of impedance
      spectroscopy analysis to determine key processes and parameters in organic bulk
      heterojunction solar cells. When carrier transport or outer interface extraction
      do not severely influence the solar cell performance, a simple method to quantify
      the open-circuit voltage loss caused by the kinetics of charge carrier
      recombination is provided, based on the determination of chemical capacitance and
      recombination resistance. This easily allows distinguishing between energetic and
      kinetic effects on photovoltage, and establishes a benchmark for the performance
      comparison of a set of different cells. A brief discussion of impedance analysis
      in the much less studied case of collection-limited solar cells is introduced. 

PMID- 26291351
TI  - Structural Origins of Conductance Fluctuations in Gold-Thiolate Molecular
      Transport Junctions.
AB  - We report detailed atomistic simulations combined with high-fidelity conductance
      calculations to probe the structural origins of conductance fluctuations in
      thermally evolving Au-benzene-1,4-dithiolate-Au junctions. We compare the
      behavior of structurally ideal junctions (where the electrodes are modeled as
      flat surfaces) to structurally realistic, experimentally representative junctions
      resulting from break-junction simulations. The enhanced mobility of metal atoms
      in structurally realistic junctions results in significant changes to the
      magnitude and origin of the conductance fluctuations. Fluctuations are larger by
      a factor of 2-3 in realistic junctions compared to ideal junctions. Moreover, in
      junctions with highly deformed electrodes, the conductance fluctuations arise
      primarily from changes in the Au geometry, in contrast to results for junctions
      with nondeformed electrodes, where the conductance fluctuations are dominated by
      changes in the molecule geometry. These results provide important guidance to
      experimentalists developing strategies to control molecular conductance, and also
      to theoreticians invoking simplified structural models of junctions to predict
      their behavior. 

PMID- 26291352
TI  - Unusual Bonding in Platinum Carbido Clusters.
AB  - Vibrational spectroscopy and density functional theory calculations are used to
      determine the structures of small gas-phase platinum carbido clusters PtnC(+), n
      = 3-5. The carbon atom is found to prefer three-coordinate binding sites near the
      center of the cluster, in contrast to most previously investigated adatoms on
      transition metal clusters. The Pt3C unit is particularly stable, and binding of
      the carbon atom also leads to significant rearrangement of the metal framework
      when compared to the bare clusters. 

PMID- 26291353
TI  - High Open-Circuit Voltage Solar Cells Based on Organic-Inorganic Lead Bromide
      Perovskite.
AB  - Mesoscopic solar cells, based on solution-processed organic-inorganic perovskite
      absorbers, are a promising avenue for converting solar to electrical energy. We
      used solution-processed organic-inorganic lead halide perovskite absorbers, in
      conjunction with organic hole conductors, to form high voltage solar cells. There
      is a dire need for low-cost cells of this type, to drive electrochemical
      reactions or as the high photon energy cell in a system with spectral splitting.
      These perovskite materials, although spin-coated from solution, form highly
      crystalline materials. Their simple synthesis, along with high chemical
      versatility, allows tuning their electronic and optical properties. By judicious
      selection of the perovskite lead halide-based absorber, matching organic hole
      conductor, and contacts, a cell with a ~ 1.3 V open circuit voltage was made.
      While further study is needed, this achievement provides a general guideline for
      additional improvement of cell performance. 

PMID- 26291354
TI  - Exploiting Structured Environments for Efficient Energy Transfer: The Phonon
      Antenna Mechanism.
AB  - A nontrivial interplay between quantum coherence and dissipative environment
      driven dynamics is becoming increasingly recognized as the key for efficient
      energy transport in photosynthetic pigment-protein complexes, and converting
      these biologically inspired insights into a set of design principles that can be
      implemented in artificial light-harvesting systems has become an active research
      field. Here we identify a specific design principle, the phonon antenna, by which
      interpigment coherence is able to modify and optimize the way that excitations
      spectrally sample their local environmental fluctuations. We provide numerical
      simulations that suggest that the Fenna-Matthews-Olson complex of green sulfur
      bacteria has an excitonic structure that is close to such an optimal operating
      point, and place the phonon antenna concept into a broader context that leads us
      to conjecture that this general design principle might well be exploited in other
      biomolecular systems. 

PMID- 26291355
TI  - Quantum Dot Solar Cells. The Next Big Thing in Photovoltaics.
AB  - The recent surge in the utilization of semiconductor nanostructures for solar
      energy conversion has led to the development of high-efficiency solar cells. Some
      of these recent advances are in the areas of synthesis of new semiconductor
      materials and the ability to tune the electronic properties through size, shape,
      and composition and to assemble quantum dots as hybrid assemblies. In addition,
      processes such as hot electron injection, multiple exciton generation (MEG),
      plasmonic effects, and energy-transfer-coupled electron transfer are gaining
      momentum to overcome the efficiency limitations of energy capture and conversion.
      The recent advances as well as future prospects of quantum dot solar cells
      discussed in this perspective provide the basis for consideration as "The Next
      Big Thing" in photovoltaics. 

PMID- 26291356
TI  - Understanding the Density Functional Dependence of DFT-Calculated Electronic
      Couplings in Organic Semiconductors.
AB  - We present an analysis of the magnitude of density functional theory (DFT)
      calculated intermolecular electronic couplings (transfer integrals) in organic
      semiconductors to give insight into the impact that the choice of functional has
      on the value of this parameter, which is particularly important in the context of
      charge transport. The major factor determining the magnitude of the calculated
      transfer integrals is the amount of nonlocal Hartree-Fock (HF) exchange within a
      given functional, with the transfer integrals increasing by up to a factor of 2
      when going from 0 to 100% HF exchange for a series of conventional functionals.
      We underline that these variations in the transfer integrals are in fact to be
      expected, with the computed transfer integrals evolving linearly with the amount
      of HF exchange. We also use a long-range corrected functional to tune the
      contributions of (semi)local and nonlocal HF exchanges and highlight their
      respective roles as a function of intermolecular separation. 

PMID- 26291357
TI  - Exceptional Mechanical Stability of Highly Porous Zirconium Metal-Organic
      Framework UiO-66 and Its Important Implications.
AB  - Metal-organic frameworks (MOFs) with high porosity usually exhibit weak
      mechanical stabilities, in particular, rather low stabilities against shear
      stress. This limitation remains one of the bottlenecks for certain applications
      of porous MOFs, such as gas storage or separation that requires dense packing of
      the MOF powders under mechanical compression without collapsing the pores. We
      found that UiO-66, a prototypical Zr-MOF with high porosity, exhibits unusually
      high shear stability. Its minimal shear modulus (Gmin = 13.7 GPa) is an order of
      magnitude higher than those of other benchmark highly porous MOFs (e.g., MOF-5,
      ZIF-8, HKUST-1), approaching that of zeolites. Our analysis clearly shows that
      the exceptional mechanical stability of UiO-66 is due to its high framework
      connections (i.e., the high degree of coordination of Zr-O metal centers to the
      organic linkers). Our work thus provides important guidelines for developing new
      porous MOFs targeting at high mechanical stabilities. 

PMID- 26291358
TI  - An Optocatalytic Model for Semiconductor-Catalyst Water-Splitting Photoelectrodes
      Based on In Situ Optical Measurements on Operational Catalysts.
AB  - The optical properties of electrocatalysts are important for photoelectrochemical
      water splitting because colored catalysts on the surface of semiconductor
      photoelectrodes parasitically absorb photons and lower the system efficiency. We
      present a model that describes the coupling of colored oxygen evolution reaction
      (OER) electrocatalyst thin films with semiconductor photoelectrodes. We use this
      model to define an "optocatalytic" efficiency (Phio-c) based on experimental
      optical and electrokinetic data collected in basic solution. Because transition
      metal oxides, hydroxides, and oxyhydroxides often exhibit electrochromism, in
      situ spectroelectrochemistry is used to quantify the optical absorption of active
      NiOx, CoOx, NiCoOx, Ni0.9Fe0.1Ox, and IrOx catalyst films at OER potentials. For
      the highest-activity Ni0.9Fe0.1Ox catalyst, Phio-c is maximized (0.64) for a
      thickness of ~0.4 nm (~2 monolayers). This work quantitatively shows that
      ultrathin catalyst films are appropriate to optimize the performance of water
      splitting photoelectrodes and thus assists in the design and study of efficient
      photoelectrochemical water-splitting devices. 

PMID- 26291359
TI  - Temperature Dependence of Logarithmic-like Relaxational Dynamics of Hydrated
      tRNA.
AB  - The dynamics of RNA within the beta-relaxation region of 10 ps to 1 ns is crucial
      to its biological function. Because of its simpler chemical building blocks and
      the lack of the side methyl groups, faster relaxational dynamics of RNA compared
      to proteins can be expected. However, the situation is actually opposite. In this
      work, the relaxational dynamics of tRNA is measured by quasielastic neutron
      scattering and analyzed using the mode coupling theory, originally developed for
      glass-forming liquids. Our results reveal that the dynamics of tRNA follows a log
      decay within the beta-relaxation region, which is an important trait demonstrated
      by the dynamics of proteins. The dynamics of hydrated tRNA and lysozyme compared
      in the time domain further demonstrate that the slower dynamics of tRNA relative
      to proteins originates from the difference in the folded states of tRNA and
      proteins, as well as the influence of their hydration water. 

PMID- 26291360
TI  - Intermolecular Coulombic Decay in Biology: The Initial Electron Detachment from
      FADH(-) in DNA Photolyases.
AB  - Intermolecular coulombic decay (ICD) is an efficient mechanism of low-energy
      electron generation in condensed phases and is discussed as their potential
      source in living cells, tissues, and materials. The first example of ICD as an
      operating mechanism in real biological systems, that is, in the DNA repair
      enzymes photolyases, is presented. Photolyase function involves light-induced
      electron detachment from a reduced flavin adenine dinucleotide (FADH(-)),
      followed by its transfer to the DNA-lesion triggering repair of covalently bound
      nucleobase dimers. Modern quantum chemical methods are employed to demonstrate
      that the transferred electron is efficiently generated via a resonant ICD process
      between the antenna pigment and the FADH(-) cofactors. 

PMID- 26291361
TI  - Correction to "Thermal Narrowing of the Electronic Bandwidths in Organic
      Molecular Semiconductors: Impact of the Crystal Thermal Expansion".

PMID- 26291362
TI  - A New Paradigm to Half-Metallicity in Graphene Nanoribbons.
AB  - In contrast to the well-recognized transverse-electric-field-induced half
      metallicity in zigzag graphene nanoribbons, here, we demonstrate by first
      principles calculations that zigzag graphene nanoribbons sandwiched between
      hexagonal boron nitride nanoribbons or sheets can be tuned into half-metal simply
      by a bias voltage or a moderate compressive strain. The half-metallicity is
      attributed to an enhanced coupling effect of spontaneous polarization and
      asymmetrical exchange correlation along the ribbon width. The findings should
      open a viable route for efficient spin-resolved band engineering in graphene
      based devices that are compatible with the current technology of the
      semiconductor industry. 

PMID- 26291363
TI  - Intermolecular Interactions in Dye-Sensitized Solar Cells: A Computational
      Modeling Perspective.
AB  - We present a unified overview of our recent activity on the modeling of relevant
      intermolecular interactions occurring in dye-sensitized solar cells (DSCs). The
      DSC is an inherent complex system, whose efficiency is essentially determined by
      the interrelated phenomena occurring at the multiple molecular-semiconductor
      electrolyte heterointerfaces. In this Perspective, we illustrate the basic
      methodology and selected applications of computational modeling of dye-dye and
      dye-coadsorbent intermolecular interactions taking place at the dye-sensitized
      interface. We show that the proposed methodology offers a realistic picture of
      aggregation phenomena among surface-adsorbed dyes and nicely describes
      semiconductor surfaces cosensitized by different dyes. The information acquired
      from this type of studies might constitute the basis for an integrated multiscale
      computational description of the device functioning, including all of the
      possible interdependencies among the device constituents, which may further boost
      the DSCs efficiency. We believe that this direction should be the target of
      future computational research in the DSC field. 

PMID- 26291364
TI  - Multiparticle Exciton Ionization in Shallow Doped Carbon Nanotubes.
AB  - Shallow hole doping in small-diameter semiconducting carbon nanotubes with a
      valley degeneracy is predicted to result in the resonant ionization of excitons
      into free electron-hole pairs. This mechanism, which relies on the chirality of
      the electronic states, causes excitons to decay with high efficiencies where the
      rate scales as the square of the dopant density. Moreover, multiparticle exciton
      ionization can account for delocalized fluorescence quenching when a few holes
      per micrometer of tube length are present. 

PMID- 26291365
TI  - Dynamic Trap Formation and Elimination in Colloidal Quantum Dots.
AB  - Using first-principles simulations on PbS and CdSe colloidal quantum dots, we
      find that surface defects form in response to electronic doping and charging of
      the nanoparticles. We show that electronic trap states in nanocrystals are
      dynamic entities, in contrast with the conventional picture wherein traps are
      viewed as stable electronic states that can be filled or emptied, but not created
      or destroyed. These traps arise from the formation or breaking of atomic dimers
      at the nanoparticle surface. The dimers' energy levels can reside within the
      bandgap, in which case a trap is formed. Fortunately, we are also able to
      identify a number of shallow-electron-affinity cations that stabilize the
      surface, working to counter dynamic trap formation and allowing for trap-free
      doping. 

PMID- 26291366
TI  - Role of Photoexcitation and Field Ionization in the Measurement of Accurate Oxide
      Stoichiometry by Laser-Assisted Atom Probe Tomography.
AB  - The addition of pulsed lasers to atom probe tomography (APT) extends its high
      spatial and mass resolution capability to nonconducting materials, such as
      oxides. For a prototypical metal oxide, MgO, the measured stoichiometry depends
      strongly on the laser pulse energy and applied voltage. Very low laser energies
      (0.02 pJ) and high electric fields yield optimal stoichiometric accuracy.
      Correlated APT and aberration-corrected transmission electron microscopy (TEM)
      are used to establish the high density of corner and terrace sites on MgO sample
      surfaces before and after APT. For MgO, long-lifetime photoexcited holes
      localized at oxygen corner sites can assist in the creation of oxygen neutrals
      that may spontaneously desorb either as atomic O or as molecular O2. The observed
      trends are best explained by the relative field-dependent ionization of
      photodesorbed O or O2 neutrals. These results emphasize the importance of
      considering electronic excitations in APT analysis of oxide materials. 

PMID- 26291367
TI  - Storage of Lithium in Hydrothermally Synthesized GeO2 Nanoparticles.
AB  - Amorphous GeO2 nanoparticles were prepared via a surfactant-assisted hydrothermal
      process. The effect of the reaction temperature and the surfactant concentration
      on the morphology of GeO2 particles were investigated. Particles of less than 300
      nm were obtained when using 1,2-diaminopropane surfactant in a synthesis carried
      out at 180(?)C. The synthesized germanium oxide nanoparticles were evaluated for
      their utility as the active anode material in Li-ion batteries. The electrode
      prepared with this material exhibited a stable capacity ~600 mAh g(-1) at 0.2 C
      rate for up to 150 cycles in a conventional electrolyte containing ethylene
      carbonate (EC). The cyclability of the GeO2 nanoparticle electrode was further
      improved by using a fluorinated ethylene carbonate (FEC) based electrolyte, which
      showed capacities greater than 600 mAh g(-1) and retained more than 96% of their
      capacity after 500 cycles at 0.2 C rate. The effect of different electrolyte
      systems was studied by using electrochemical impedance spectroscopy and electron
      microscopy. 

PMID- 26291368
TI  - Control Mechanisms of Photoisomerization in Protonated Schiff Bases.
AB  - We performed ab initio excited-state molecular dynamics simulations of a gas
      phase photoexcited protonated Schiff base (C1-N2?C3-C4?C5-C6) to search for
      control mechanisms of its photoisomerization. The excited molecule twists by ~90
      degrees  around either the N2C3 bond or the C4C5 bond and relaxes to the ground
      electronic state through a conical intersection with either a trans or cis
      outcome. We show that a large initial distortion of several dihedral angles and a
      specific normal vibrational mode combining pyramidalization and double-bond
      twisting can lead to a preferential rotation of atoms around the C4C5 bond. We
      also show that selective pretwisting of several dihedral angles in the initial
      ground state thermal ensemble (by analogy to a protein pocket) can significantly
      increase the fraction of photoreactive (cis -> trans) trajectories. We
      demonstrate that new ensembles with higher degrees of control over the
      photoisomerization reaction can be obtained by a computational directed evolution
      approach on the ensembles of molecules with the pretwisted geometries. 

PMID- 26291369
TI  - On the Inapplicability of Electron-Hopping Models for the Organic Semiconductor
      Phenyl-C61-butyric Acid Methyl Ester (PCBM).
AB  - Phenyl-C61-butyric acid methyl ester (PCBM) is one of the most popular
      semiconductors in organic photovoltaic cells, but the electron-transport
      mechanism in the microcrystalline domains of this material as well as its
      preferred packing structure remain unclear. Here we use density functional theory
      to calculate electronic-coupling matrix elements, reorganization energies, and
      activation energies for available experimental and model crystal structures. We
      find that the picture of an excess electron hopping from one fullerene to another
      does not apply for any of the crystalline phases, rendering traditional rate
      equations inappropriate. We also find that the cohesive energy increases in the
      order body-centered-cubic < hexagonal < simple cubic < monoclinic < triclinic,
      independently of the type of dispersion correction used. Our results indicate
      that the coupled electron-ion dynamics needs to be solved explicitly to obtain a
      realistic description of charge transfer in this material. 

PMID- 26291370
TI  - What Stabilizes the LinPn Inorganic Double Helices?
AB  - Recently, inorganic double-helical structures based on simple lithium and
      phosphorus salts have been demonstrated. We have analyzed the nature of bonding
      in these double helices of LinPn (n = 7-9). Similar to DNA, noncovalent
      interactions and cooperativity play an important role in stabilizing the
      inorganic double helices. Cooperativity imparts an additional stabilization of
      4.5 to 10.1 kcal/mol per Li-P pair. In addition, the ionicity of Li-P units
      further augments the stability of these inorganic double-helix structures in
      contrast with the canonical base pairs in DNA, where noncovalent interactions
      determine the duplex stability. Unwinding is shown to be unfavorable, and
      cleavage of a few edge Li-P bonds leads to spontaneous self-healing into the
      intact double-helix tract. 

PMID- 26291371
TI  - Effective Mass-Driven Structural Transition in a Mn-Doped ZnS Nanoplatelet.
AB  - Mn doping in ZnS nanoplatelets has been shown to induce a structural transition
      from the wurtzite to the zinc blende phase. We trace the origin of this
      transition to quantum confinement effects, which shift the valence band maximum
      of the wurtzite and zinc blende polymorphs of ZnS at different rates as a
      function of the nanocrystal size, arising from different effective hole masses in
      the two structures. This modifies the covalency associated with Mn incorporation
      and is reflected in the size-dependent binding energy difference for the two
      structures. 

PMID- 26291372
TI  - Seamless and Accurate Modeling of Organic Molecular Materials.
AB  - The near endless possibilities for assembling molecular materials has long posed
      a difficult challenge for theory. All crystal-structure prediction methods
      acknowledge the crucial contribution of van der Waals or dispersion interactions,
      but few go beyond a pairwise additive description of dispersion, ignoring its
      many-body nature. Here we use two databases to show how a many-body approach to
      dispersion can seamlessly model both solid and gas-phase interactions within the
      coveted "chemical accuracy" benchmark, while the underlying pairwise approach
      fails for solid-state interactions due to the absence of many-body polarization
      and energy contributions. Our results show that recently developed methods that
      treat the truly collective nature of dispersion interactions are able to reach
      the accuracy required for predicting molecular materials, when coupled with
      nonempirical density functionals. 

PMID- 26291373
TI  - Unprecedented External Electric Field Effects on S-Nitrosothiols: Possible
      Mechanism of Biological Regulation?
AB  - Reactions of S-nitrosothiols (RSNOs), ubiquitous carriers of nitric oxide NO and
      its physiological activity, are tightly regulated in biological systems, but the
      mechanisms of this regulation are not well understood. Here, we computationally
      demonstrate that RSNO properties can be dramatically altered by biologically
      accessible external electric fields (EEFs) by modulation of the two minor
      antagonistic resonance structures of RSNOs, which have opposite formal charge
      distributions and bonding patterns. As these resonance contributions relate to
      the two competing modes of RSNO reactivity with nucleophiles, via N- or S-atom
      directed nucleophilic attack, EEFs are predicted to be efficient in controlling
      biologically important RSNO reactions with thiols. For instance, EEF catalysis
      might be one of the mechanisms behind the high selectivity of protein trans-S
      nitrosation reactions, or putative nitroxyl HNO formation via RSNO S-thiolation
      reactions. 

PMID- 26291374
TI  - Self-Induced Surfactant Transport along Discontinuous Liquid-Liquid Interfaces.
AB  - While the Marangoni-stress-driven spreading of surfactants along continuous fluid
      interfaces is a well-studied problem, we demonstrate experimentally that swift
      and efficient surfactant transport can also occur along discontinuous interfaces.
      We used chemical surface patterning to create arrays of discrete drops and liquid
      bridges immersed inside a second immiscible liquid. Surface-active compounds
      introduced at one end of the linear array are transported along the array via
      surfactant-induced interfacial convection at a rate by far exceeding diffusion.
      We believe this mechanism to be relevant to the application of surfactants in
      enhanced oil recovery, where oil-water interfaces are likely to be discontinuous.
      Marangoni flows can provide access to dead-end pores and low-permeability regions
      that are otherwise bypassed by conventional pressure-driven waterfloods. 

PMID- 26291375
TI  - Modeling Dye-Sensitized Solar Cells: From Theory to Experiment.
AB  - Density functional theory (DFT) and time-dependent DFT are useful computational
      approaches frequently used in the dye-sensitized solar cell (DSSC) community in
      order to analyze experimental results and to clarify the elementary processes
      involved in the working principles of these devices. Indeed, despite these
      significant contributions, these methods can provide insights that go well beyond
      a purely descriptive aim, especially when suitable computational approaches and
      methodologies for interpreting and validating the computational outcomes are
      developed. In the present contribution, the possibility of using recently
      developed computational approaches to design and interpret the macroscopic
      behavior of DSSCs is exemplified by the study of the performances of three new
      TiO2-based DSSCs making use of organic dyes, all belonging to the expanded
      pyridinium family. 

PMID- 26291376
TI  - Nano-Enabled Photovoltaics. Progress in Materials and Methodologies.

PMID- 26291377
TI  - Inhomogeneous Quenching as a Limit of the Correlation Between Fluorescence
      Polarization and Conformation of Single Molecules.
AB  - The photophysical properties of conjugated polymers (CPs) largely depend on the
      interactions between the CP and its environment. We present a study of two
      polymers with identical conjugated backbones, bare and insulated, that showed
      different fluorescence excitation modulation depth histograms. However, the
      polarization differences are not related to differences in conformation, as
      commonly believed, but to the existence of "dark" chromophores in the bare
      polymer that are statically quenched. This results in inhomogeneous quenching of
      the polymer chain that breaks the correlation between excitation fluorescence
      polarization and conjugated polymer chain conformation. 

PMID- 26291378
TI  - Trinuclear and Tetranuclear Re(I) Rings Connected with Phenylene, Vinylene, and
      Ethynylene Chains: Synthesis, Photophysics, and Redox Properties.
AB  - A series of highly luminescent trinuclear and tetranuclear ring-shaped Re(I)
      complexes wherein the Re units are linked with rigid bidentate phosphine ligands,
      namely, bis(diphenylphosphino)-p-phenylene, -trans-vinylene, and -ethynylene,
      were synthesized and fully characterized. Their strong emissive properties and
      the long lifetimes of their triplet metal-to-ligand charge transfer excited
      states originate primarily from enhanced, rigidity-induced interligand
      interactions between the 2,2'-bipyridine (bpy) ligand and the phenyl groups of
      the phosphine ligands. In addition, another type of interligand interaction was
      also observed between the bpy ligand and the phosphine-bridging group; this
      interaction also strongly affected the photophysical and redox properties of the
      Re-rings. 

PMID- 26291380
TI  - Characterization of the 1,1-HCl Elimination Reaction of Vibrationally Excited
      CD3CHFCl Molecules and Assignment of Threshold Energies for 1,1-HCl and 1,2-DCl
      plus 1,1-HF and 1,2-DF Elimination Reactions.
AB  - Vibrationally excited CD3CHFCl molecules with 96 kcal mol(-1) of energy were
      generated by the recombination of CD3 and CHFCl radicals in a room-temperature
      bath gas. The four competing unimolecular decomposition reactions, namely, 1,1
      HCl and 1,2-DCl elimination and 1,1-HF and 1,2-DF elimination, were observed, and
      the individual rate constants were measured. The product branching fractions are
      0.60, 0.27, 0.09, and 0.04 for 1,2-DCl, 1,1-HCl, 1,2-DF, and 1,1-HF elimination,
      respectively. Electronic structure calculations were used to define models of the
      four transition states. The statistical rate constants calculated from these
      models were compared to the experimental rate constants. The assigned threshold
      energies with +/-2 kcal mol(-1) uncertainty are 60, 72, 65, and 74 kcal mol(-1)
      for the 1,2-DCl, 1,1-HCl, 1,2-DF, and 1,1-HF reactions, respectively. The loose
      structure of the 1,1-HX transition states, which is exemplified by the order of
      magnitude larger pre-exponential factor relative to the 1,2-HX elimination
      reactions, compensates for the high threshold energy; thus, the 1,1-HX
      elimination reaction rates can compete with the 1,2-HX elimination reactions for
      high levels of vibrational excitation in CD3CHFCl. The 1,1-HCl and 1,1-HF
      reactions are observed via the CD2?CDF and CD2?CDCl products formed from
      isomerization of the CD3CF and CD3CCl carbenes. These D-atom migration reactions
      are discussed, and the possibility of tunneling is evaluated. The transition
      states developed from the 1,1-HCl and 1,1-HF reactions of CD3CHFCl are compared
      to models for the HCl and HF elimination reactions of CHF2Cl, CHFCl2, and CH2FCl.

PMID- 26291379
TI  - Monitoring Effect of Human Papillomavirus Vaccines in US Population, Emerging
      Infections Program, 2008-2012.
AB  - In 2007, five Emerging Infections Program (EIP) sites were funded to determine
      the feasibility of establishing a population-based surveillance system for
      monitoring the effect of human papillomavirus (HPV) vaccine on pre-invasive
      cervical lesions. The project involved active population-based surveillance of
      cervical intraepithelial neoplasia grades 2 and 3 and adenocarcinoma in situ as
      well as associated HPV types in women >18 years of age residing in defined
      catchment areas; collecting relevant clinical information and detailed HPV
      vaccination histories for women 18-39 years of age; and estimating the annual
      rate of cervical cancer screening among the catchment area population. The first
      few years of the project provided key information, including data on HPV type
      distribution, before expected effect of vaccine introduction. The project's
      success exemplifies the flexibility of EIP's network to expand core activities to
      include emerging surveillance needs beyond acute infectious diseases. Project
      results contribute key information regarding the impact of HPV vaccination in the
      United States. 

PMID- 26291381
TI  - Progress of Polymers from Renewable Resources: Furans, Vegetable Oils, and
      Polysaccharides.

PMID- 26291382
TI  - Interactions of Polyvinylpyrrolidone with Chlorin e6-Based Photosensitizers
      Studied by NMR and Electronic Absorption Spectroscopy.
AB  - Polyvinylpyrrolidone (PVP) can act as potential drug delivery vehicle for
      porphyrin-based photosensitizers in photodynamic therapy (PDT) to enhance their
      stability and prevent porphyrin self-association. In the present study the
      interactions of PVP (MW 10 kDa) were probed with five different derivatives of
      chlorin e6 (CE6) bearing either one of the amino acids serine, lysine, tyrosine
      or arginine, or monoamino-hexanoic acid as substituent. All derivatives of CE6
      (xCE) formed aggregates of a similar structure in aqueous buffer in the
      millimolar range. In the presence of PVP monomerization of all xCE aggregates
      could be proved by (1)H NMR spectroscopy. xCE-PVP complex formation was confirmed
      by (1)H NMR T2 relaxation and diffusion ordered spectroscopy (DOSY). (1)H(1)H
      NOESY data suggested that the xCE uptake into the PVP polymer matrix is governed
      by hydrophobic interactions. UV-vis absorption and fluorescence emission bands of
      xCE in the micromolar range revealed characteristic PVP-induced bathochromic
      shifts. The presented data point out the potential of PVP as carrier system for
      amphiphilic derivatives of chlorin e6. The capacity of PVP to monomerize xCE
      aggregates may enhance their efficiency as possible photosensitizers in PDT. 

PMID- 26291383
TI  - How does visual manipulation affect obstacle avoidance strategies used by
      athletes?
AB  - Research examining our ability to avoid obstacles in our path has stressed the
      importance of visual input. The aim of this study was to determine if athletes
      playing varsity-level field sports, who rely on visual input to guide motor
      behaviour, are more able to guide their foot over obstacles compared to
      recreational individuals. While wearing kinematic markers, eight varsity athletes
      and eight age-matched controls (aged 18-25) walked along a walkway and stepped
      over stationary obstacles (180 degrees  motion arc). Visual input was manipulated
      using PLATO visual goggles three or two steps pre-obstacle crossing and compared
      to trials where vision was given throughout. A main effect between groups for
      peak trail toe elevation was shown with greater values generated by the controls
      for all crossing conditions during full vision trials only. This may be
      interpreted as athletes not perceiving this obstacle as an increased threat to
      their postural stability. Collectively, findings suggest the athletic group is
      able to transfer their abilities to non-specific conditions during full vision
      trials; however, varsity-level athletes were equally reliant on visual cues for
      these visually guided stepping tasks as their performance was similar to the
      controls when vision is removed. 

PMID- 26291384
TI  - Ocean Research Enabled by Underwater Gliders.
AB  - Underwater gliders are autonomous underwater vehicles that profile vertically by
      changing their buoyancy and use wings to move horizontally. Gliders are useful
      for sustained observation at relatively fine horizontal scales, especially to
      connect the coastal and open ocean. In this review, research topics are grouped
      by time and length scales. Large-scale topics addressed include the eastern and
      western boundary currents and the regional effects of climate variability. The
      accessibility of horizontal length scales of order 1 km allows investigation of
      mesoscale and submesoscale features such as fronts and eddies. Because the
      submesoscales dominate vertical fluxes in the ocean, gliders have found
      application in studies of biogeochemical processes. At the finest scales, gliders
      have been used to measure internal waves and turbulent dissipation. The review
      summarizes gliders' achievements to date and assesses their future in ocean
      observation. 

PMID- 26291386
TI  - Lifetime Occupation and Late-Life Cognitive Performance Among Women.
AB  - We examined whether women who had regular jobs throughout life performed better
      cognitively than older adult housewives. Linear regression was used to compare
      global cognitive performance scores of housewives (G1) and women exposed to work
      of low (G2) and high (G3) complexity. The sample comprised 477 older adult
      Brazilian women, 430 (90.4%) of whom had performed lifelong jobs. In work with
      data, the G2 group's cognitive performance scores were 1.73 points higher (p
      =.03), and the G3 group scored 1.76 points (p =.02) higher, than the G1. In work
      with things and with people, the G3 scored, respectively, 2.04 (p <.01) and 2.21
      (p <.01) cognitive test points higher than the G1. Based on our findings we
      suggest occupation of greater complexity is associated with better cognitive
      performance in women later in life. 

PMID- 26291385
TI  - Integrative analysis of methylome and transcriptome in human blood identifies
      extensive sex- and immune cell-specific differentially methylated regions.
AB  - The relationship between DNA methylation and gene expression is complex and
      elusive. To further elucidate these relations, we performed an integrative
      analysis of the methylome and transcriptome of 4 circulating immune cell subsets
      (B cells, monocytes, CD4(+), and CD8(+) T cells) from healthy females.
      Additionally, in light of the known sex bias in the prevalence of several immune
      mediated diseases, the female datasets were compared with similar public
      available male data sets. Immune cell-specific differentially methylated regions
      (DMRs) were found to be highly similar between sexes, with an average correlation
      coefficient of 0.82; however, numerous sex-specific DMRs, shared by the cell
      subsets, were identified, mainly on autosomal chromosomes. This provides a list
      of highly interesting candidate genes to be studied in disorders with sexual
      dimorphism, such as autoimmune diseases. Immune cell-specific DMRs were mainly
      located in the gene body and intergenic region, distant from CpG islands but
      overlapping with enhancer elements, indicating that distal regulatory elements
      are important in immune cell specificity. In contrast, sex-specific DMRs were
      overrepresented in CpG islands, suggesting that the epigenetic regulatory
      mechanisms of sex and immune cell specificity may differ. Both positive and, more
      frequently, negative correlations between subset-specific expression and
      methylation were observed, and cell-specific DMRs of both interactions were
      associated with similar biological pathways, while sex-specific DMRs were linked
      to networks of early development or estrogen receptor and immune-related
      molecules. Our findings of immune cell- and sex-specific methylome and
      transcriptome profiles provide novel insight on their complex regulatory
      interactions and may particularly contribute to research of immune-mediated
      diseases. 

PMID- 26291387
TI  - Regional cerebral oxygen saturation monitoring for predicting interventional
      outcomes in patients following out-of-hospital cardiac arrest of presumed cardiac
      cause: A prospective, observational, multicentre study.
AB  - AIM: This study investigated the value of regional cerebral oxygen saturation
      (rSO2) monitoring upon arrival at the hospital for predicting post-cardiac arrest
      intervention outcomes. METHODS: We enrolled 1195 patients with out-of-hospital
      cardiac arrest of presumed cardiac cause from the Japan-Prediction of
      Neurological Outcomes in Patients Post-cardiac Arrest Registry. The primary
      endpoint was a good neurologic outcome (cerebral performance categories 1 or 2
      [CPC1/2]) 90 days post-event. RESULTS: A total of 68 patients (6%) had good
      neurologic outcomes. We found a mean rSO2 of 21%+/-13%. A receiver operating
      characteristic curve analysis indicated an optimal rSO2 cut-off of >=40% for good
      neurologic outcomes (area under the curve 0.92, sensitivity 0.81, specificity
      0.96). Good neurologic outcomes were observed in 53% (55/103) and 1% (13/1092) of
      patients with high (>=40%) and low (<40%) rSO2, respectively. Even without return
      of spontaneous circulation (ROSC) upon arrival at the hospital, 30% (9/30) of
      patients with high rSO2 had good neurologic outcomes. Furthermore, 16 patients
      demonstrating ROSC upon arrival at the hospital and low rSO2 had poor neurologic
      outcomes. Multivariate analyses indicated that high rSO2 was independently
      associated with good neurologic outcomes (odds ratio=14.07, P<0.001). Patients
      with high rSO2 showed favourable neurologic prognoses if they had undergone
      therapeutic hypothermia or coronary angiography (CPC1/2, 69% [54/78]). However,
      24% (25/103) of those with high rSO2 did not undergo these procedures and
      exhibited unfavourable neurologic prognoses (CPC1/2, 4% [1/25]). CONCLUSION: rSO2
      is a good indicator of 90-day neurologic outcomes for post-cardiac arrest
      intervention patients.

PMID- 26291388
TI  - Health-care Provider Screening and Advice for Smoking Cessation Among Smokers
      With and Without COPD: 2009-2010 National Adult Tobacco Survey.
AB  - BACKGROUND: Cigarette smoking is the predominant cause of COPD. Quitting can
      prevent development of and complications from COPD. The gold standard in
      clinician delivery of smoking cessation treatments is the 5As (ask, advise,
      assess, assist, arrange). This study assessed prevalence and correlates of self
      reported receipt of the 5A strategies among adult smokers with and without COPD.
      METHODS: Data were analyzed from 20,021 adult past-year cigarette smokers in the
      2009-2010 National Adult Tobacco Survey, a nationally representative telephone
      survey of US adults 18 years of age and older. Past-year receipt of the 5As was
      self-reported by participants who saw a clinician in the past year. Logistic
      regression was used to estimate the likelihood of receipt of each of the 5As by
      COPD status, adjusted for sociodemographic and smoking characteristics. RESULTS:
      Among smokers, those with COPD were more likely than those without COPD to report
      being asked about tobacco use (95.4% vs 85.8%), advised to quit (87.5% vs 59.4%),
      assessed for readiness to quit (63.8% vs 37.9%), offered any assistance to quit
      (58.6% vs 34.0%), and offered follow-up (14.9% vs 5.2%). In adjusted logistic
      regression models, those with COPD were significantly more likely than those
      without COPD to receive each of the 5As. CONCLUSIONS: Health professionals should
      continue to prioritize tobacco cessation counseling and treatment to smokers with
      COPD. Increased system-level changes and insurance coverage for cessation
      treatments could be used to improve the delivery of brief tobacco cessation
      counseling to all smokers, regardless of COPD status.

PMID- 26291389
TI  - Clinical outcomes and mortality associated factors in patients infected with HIV
      receiving a presumptive anti-tuberculosis treatment in a tertiary level hospital
      in Burkina Faso.
AB  - INTRODUCTION: Tuberculosis is the leading cause of death among people living with
      HIV/AIDS (PLHIV) in sub-Saharan Africa. In PLHIV, Smear-Negative Pulmonary
      Tuberculosis (SNPTB) and Extrapulmonary Tuberculosis (EPTB) are predominant.
      Presumptive anti-tuberculosis (anti-TB) treatment is often delayed leading to a
      high mortality rate. OBJECTIVES: To investigate the clinical outcomes of
      presumptive anti-TB treatment in HIV patients suspected of having TB and to
      determine the factors associated with patients' death. METHODS: We conducted a
      retrospective descriptive study from 1 January 2007 to 31 December 2008 in the
      Department of Internal Medicine of the Hospital Yalgado Ouedraogo on patients
      infected with HIV who received a presumptive anti-TB treatment. Defining patients
      with SNPTB or EPTB was based on the 2007 WHO's diagnostic algorithm of SNPTB and
      EPTB. RESULTS: One hundred and sixteen patients of the 383 (30.2%) HIV patients
      hospitalized in this period were suspected of having TB. The average CD4 count
      was 86.1 cells/ul (SD = 42.3). A SNPTB was diagnosed in 67 patients (57.8%) and a
      EPTB in 49 patients (42.2%). The median length of hospitalization duration was
      23.5 days. The average time of initiation of anti-TB treatment after admission
      was 22 days (SD = 9.2 days). Evolution during the hospital stay was favorable for
      65 patients (56.0%), unfavorable for 48 patients (41.4% or 12.5% of all
      hospitalized patients), and 3 patients (2.6%) were treatment defaulters. In a
      multivariate analysis, hospitalization duration longer than 15 days and a delay
      of anti-TB treatment initiation of more than 30 days are independent factors
      associated with patients' deaths. CONCLUSION: An urgent access to TB-diagnostic
      tools and a revision of the International algorithm for the diagnosis and
      treatment of SNPTB and EPTB in the context of HIV could help to reduce the delay
      of anti-TB treatment initiation and the mortality rate of PLHIV in sub-Saharan
      Africa.

PMID- 26291390
TI  - The Universal Language of Cataract Surgery.

PMID- 26291391
TI  - Butylated hydroxyanisole induces distinct expression patterns of Nrf2 and
      detoxification enzymes in the liver and small intestine of C57BL/6 mice.
AB  - Butylated hydroxyanisole (BHA) is widely used as an antioxidant and preservative
      in food, food packaging and medicines. Its chemopreventive properties are
      attributing to its ability to activate the transcription factor NF-E2 p45-related
      factor 2 (Nrf2), which directs central genetic programs of detoxification and
      protection against oxidative stress. This study was to investigate the
      histological changes of Nrf2 and its regulated phase II enzymes Nqo1, AKR1B8, and
      Ho-1 in wild-type (WT) and Nrf2(-/-) mice induced by BHA. The mice were given a
      200mg/kg oral dose of BHA daily for three days. Immunohistochemistry revealed
      that, in the liver from WT mice, BHA increased Nqo1 staining in hepatocytes,
      predominately in the pericentral region. In contrast, the induction of AKR1B8
      appeared mostly in hepatocytes in the periportal region. The basal and inducible
      Ho-1 was located almost exclusively in Kupffer cells. In the small intestine from
      WT mice, the inducible expression patterns of Nqo1 and AKR1B8 were nearly
      identical to that of Nrf2, with more intense staining in the villus than that the
      crypt. Conversely, Keap1 was more highly expressed in the crypt, where the
      proliferative cells reside. Our study demonstrates that BHA elicited differential
      expression patterns of phase II-detoxifying enzymes in the liver and small
      intestine from WT but not Nrf2(-/-) mice, demonstrating a cell type specific
      response to BHA in vivo. 

PMID- 26291392
TI  - Polyhedra structures and the evolution of the insect viruses.
AB  - Polyhedra represent an ancient system used by a number of insect viruses to
      protect virions during long periods of environmental exposure. We present high
      resolution crystal structures of polyhedra for seven previously uncharacterised
      types of cypoviruses, four using ab initio selenomethionine phasing (two of these
      required over 100 selenomethionine crystals each). Approximately 80% of residues
      are structurally equivalent between all polyhedrins (pairwise rmsd ? 1.5 A),
      whilst pairwise sequence identities, based on structural alignment, are as little
      as 12%. These structures illustrate the effect of 400 million years of evolution
      on a system where the crystal lattice is the functionally conserved feature in
      the face of massive sequence variability. The conservation of crystal contacts is
      maintained across most of the molecular surface, except for a dispensable virus
      recognition domain. By spreading the contacts over so much of the protein surface
      the lattice remains robust in the face of many individual changes. Overall these
      unusual structural constraints seem to have skewed the molecule's evolution so
      that surface residues are almost as conserved as the internal residues.

PMID- 26291393
TI  - The Clinical Outcome of Anatomical Reattachment of the TFCC to the Ulnar Fovea
      using an ECU Half-Slip and an Interference Screw.
AB  - We developed an original reattachment technique using a half-slip of the extensor
      carpi ulnaris (ECU) tendon with a very small titanium interference screw for
      chronic foveal avulsion of the TFCC. The clinical outcome of 66 wrists with
      foveal detachment of the TFCC treated by this procedure was examined.A distally
      based ECU half-slip was harvested, inserted into the TFCC, sutured to the remnant
      of the TFCC, and pulled out through a 2.5-mm bone tunnel at the centre of the
      fovea. The ECU half-slip was subsequently anchored to the ulnar fovea with a
      small titanium interference screw. We evaluated 66 wrists of 65 patients with a
      minimum follow-up of 1 year. Ulnar variance was neutral in 47 wrists, negative in
      5 and positive in 14 wrists. Causes of injury were falls in 34 patients, traffic
      accidents in 12, sports activities in 9, labour in 2 and unknown in 8 patients.
      In the positive variance wrists, ulnar shortening was performed before the
      reattachment. The clinical outcome was evaluated using our original DRUJ
      evaluating system.Preoperatively, severe wrist pain was reported in 50 wrists and
      moderate pain in 16 wrists. Severe no-endpoint DRUJ instability was noted in 65
      wrists, while 1 wrist demonstrated moderate DRUJ instability. Only 2 wrists had
      supination loss by 20 degrees. At the final follow-up, no pain was felt in 55
      wrists, mild pain in 3 wrists, and 8 patients had moderate pain. One wrist
      exhibited a 30-degree loss of supination. The DRUJ was stable in 55 wrists,
      mildly unstable in 3, moderately unstable in 4 and severely unstable in 4 wrists.
      There were 50 excellent, 9 good, 3 fair and 4 poor results.The technique of
      anatomical reattachment of the TFCC to the ulnar fovea using an ECU half-slip
      tendon is effective for chronic foveal avulsion of the TFCC with severe DRUJ
      instability. 

PMID- 26291394
TI  - Muscle force prediction: can we rely on musculoskeletal model estimations? A case
      study on push force exertions with the upper limb.

PMID- 26291395
TI  - Efflux transport of chrysin and apigenin sulfates in HEK293 cells overexpressing
      SULT1A3: The role of multidrug resistance-associated protein 4 (MRP4/ABCC4).
AB  - Efflux transport is a critical determinant to the pharmacokinetics of sulfate
      conjugates. Here we aimed to establish SULT1A3 stably transfected HEK293 cells,
      and to determine the contributions of BCRP and MRP transporters to excretion of
      chrysin and apigenin sulfates. The cDNA of SULT1A3 was stably introduced into
      HEK293 cells using a lentiviral vector, generating a sulfonation active cell line
      (i.e., SULT293 cells). Identification of sulfate transporters was achieved
      through chemical inhibition (using chemical inhibitors) and biological inhibition
      (using short-hairpin RNAs (shRNAs)) methods. Sulfated metabolites were rapidly
      generated and excreted upon incubation of SULT293 cells with chrysin and
      apigenin. Ko143 (a selective BCRP inhibitor) did not show inhibitory effects on
      sulfate disposition, whereas the pan-MRP inhibitor MK-571 caused significant
      reductions (38.5-64.3%, p<0.001) in sulfate excretion and marked elevations (160
      243%, p<0.05) in sulfate accumulation. Further, two efflux transporters (BCRP and
      MRP4) expressed in the cells were knocked-down by shRNA-mediated silencing.
      Neither sulfate excretion nor sulfate accumulation was altered in BCRP knocked
      down cells as compared to scramble cells. By contrast, MRP4 knock-down led to
      moderate decreases (17.1-20.6%, p<0.05) in sulfate excretion and increases (125
      135%, p<0.05) in sulfate accumulation. In conclusion, MRP4 was identified as an
      exporter for chrysin and apigenin sulfates. The SULT1A3 modified HEK293 cells
      were an appropriate tool to study SULT1A3-mediated sulfonation and to
      characterize BCRP/MRP4-mediated sulfate transport. 

PMID- 26291396
TI  - Atypical signaling of metabotropic glutamate receptor 1 in human melanoma cells.
AB  - The metabotropic glutamate 1 (mGlu1) receptor has emerged as a novel target for
      the treatment of metastatic melanoma and various other cancers. Our laboratory
      has demonstrated that a selective, non-competitive mGlu1 receptor antagonist
      slows human melanoma growth in vitro and in vivo. In this study, we sought to
      determine if the activation of a canonical G protein-dependent signal
      transduction cascade, which is often used as an output of mGlu1 receptor activity
      in neuronal cells, correlated with mGlu1 receptor-mediated melanoma cell
      viability. Glutamate, the endogenous ligand of mGlu1 receptors, significantly
      increased melanoma cell viability, but did not stimulate phosphoinositide (PI)
      hydrolysis in several human melanoma cell lines. In contrast, melanoma cell
      viability was not increased by quisqualate, a highly potent mGlu1 receptor
      agonist, or DHPG, a selective group I mGlu receptor agonist. Similarly to
      glutamate, quisqualate also failed to stimulate PI hydrolysis in mGlu1 receptor
      expressing melanoma cells. These results suggest that the canonical G protein
      dependent signal transduction cascade is not coupled to mGlu1 receptors in all
      human melanoma cells. On the other hand, dynamin inhibition selectively decreased
      viability of mGlu1 receptor-expressing melanoma cells, suggesting that a
      mechanism requiring internalization may control melanoma cell viability. Taken
      together, these data demonstrate that the approaches commonly used to study mGlu1
      receptor function and signaling in other systems may be inappropriate for
      studying mGlu1 receptor-mediated melanoma cell viability. 

PMID- 26291397
TI  - Allogeneic mesenchymal precursor cells (MPCs) combined with an osteoconductive
      scaffold to promote lumbar interbody spine fusion in an ovine model.
AB  - BACKGROUND: Advances in immunomagnetic cell sorting have enabled isolation and
      purification of pleuripotent stem cells from marrow aspirates and have expanded
      stem cell therapies to include allogeneic sources. PURPOSE: This study aimed to
      determine the safety and efficacy of allogeneic mesenchymal precursor cells
      (MPCs) combined with an osteoconductive scaffold in lumbar interbody spinal
      fusion using an ovine model. STUDY DESIGN: Thirty-two skeletally mature ewes
      underwent a single-level interbody fusion procedure using a Polyetheretherketone
      fusion cage supplemented with either iliac crest autograft (AG) or an
      osteconductive scaffold (Mastergraft Matrix, Medtronic, Memphis, TN, USA) with
      2.5*10(6) MPCs, 6.25*10(6) MPCs, or 12.5*10(6) MPCs. METHODS: Plain radiographs
      and computed tomography scans were scored for bridging bone at multiple points
      during healing and at necropsy. The biomechanical competency of fusion was scored
      by manual palpation and quantified using functional radiographs at necropsy.
      Postnecropsy histopathology and histomorphometric analysis assessed the local
      response to MPC treatment and quantified the volume and connectivity of newly
      formed bridging bone. Safety was assessed by serum biochemistry, hematology, and
      organ histopathology. RESULTS: Mesenchymal precursor cell treatment caused no
      adverse systemic or local tissue responses. All analyses indicated MPCs combined
      with an osteoconductive scaffold achieved similar or better fusion success as AG
      treatment after 16 weeks, and increasing the MPC dose did not enhance fusion.
      Manual palpation of the fusion site indicated more than 75% of MPC-treated and
      65% of AG-treated animals achieved rigid fusion, which was corroborated with
      functional radiography. Computed tomography fusion scores indicated all animals
      in the MPC- and AG-treatment groups were fused at 16 weeks, yet X-ray scores
      indicated only 67% of the AG-treated animals were fused. Histomorphometry
      analyses showed equivalent outcomes for fusion connectivity and bony fusion area
      for MPC- and AG-treated groups. Approximately 6% residual graft material remained
      in the MPC-treated fusion sites at 16 weeks. CONCLUSIONS: Adult allogeneic MPCs
      delivered using an osteoconductive scaffold were both safe and efficacious in
      this ovine spine interbody fusion model. These results support the use
      ofallogeneic MPCs as an alternative to AG for lumbar interbody spinal fusion
      procedures.

PMID- 26291398
TI  - Comparison of agreement of cervical spine degenerative pathology findings in
      magnetic resonance imaging studies.
AB  - BACKGROUND CONTEXT: Magnetic resonance imaging (MRI) is often used in the
      evaluation of degenerative conditions of the cervical spine. However, the
      agreement of interpreting and reporting varying degenerative findings on cervical
      MRI has not been well assessed. PURPOSE: This study aimed to compare the inter
      rater and intra-rater agreement of MRI findings between common degenerative
      findings of the cervical spine. STUDY DESIGN: A retrospective diagnostic study
      was used as study design. PATIENT SAMPLE: The sample consisted of 48 patients who
      underwent routine cervical spine MRI at our institution between January 2011 and
      June 2012. OUTCOME MEASURES: Reviewers evaluated each MRI study at each vertebral
      level for disc hydration, disc space height, central stenosis, foraminal
      stenosis, end plate changes, spondylolisthesis, and cord signal change. METHODS:
      A panel of two orthopedic spine surgeons and four musculoskeletal radiologists
      independently reviewed 48 sets of T2-weighted axial and sagittal MRI sequences
      for a series of preselected criteria, and their findings were compared with those
      of the other panelists to determine inter-rater agreement. Each panelist also re
      reviewed the first 10 studies to determine intra-rater agreement. Absolute inter
      rater and intra-rater agreements were then calculated and compared for different
      findings. A modified analysis ignored disagreements between the least severe
      grades of findings to determine the inter-rater and intra-rater agreements of the
      most clinically important severity grades. RESULTS: Absolute inter-rater
      agreement ranged from 54.6% to 95.0%. Disc hydration (54.6%), central stenosis
      (72.7%), and foraminal stenosis (73.1%) demonstrated the lowest inter-rater
      agreement, whereas spondylolisthesis (95.0%) and cord signal change (92.9%)
      demonstrated the highest agreement. The modified analysis found better inter
      rater agreement, ranging from 80.9% to 95.0%. Absolute intra-rater agreement
      ranged from 74.2% to 94.7%. The modified analysis again found better agreement,
      ranging from 85.0% to 94.7%. As would be expected, overall intra-rater agreement
      (81.6%, 95% CI 78.9%-84.3%) was higher than inter-rater agreement (75.7%, 95% CI
      74.4%-77.0%). The clinical specialty of the reviewer had no significant impact on
      inter- or intra-rater agreement. CONCLUSIONS: MRI findings play an important role
      in the management of patients with cervical spine conditions. For this reason,
      consistent descriptions of these findings are essential and physicians should be
      aware of the relative reliability of these findings. This systematic study
      developed standardized grading criteria and nomenclature for common clinically
      significant MRI findings in the cervical spine. Even in this optimized research
      setting, we found significant ranges in agreement across these MRI findings. In
      the clinical setting, inter- and intra-rater agreements may be lower, and the
      range of agreements between findings may be greater. Physicians should be aware
      of inconsistencies inherent in the interpretation of cervical MRI findings and
      should be aware that some findings demonstrate lower agreement than others.

PMID- 26291399
TI  - Selection of the upper vertebra to be instrumented in the treatment of
      thoracolumbar and lumbar adolescent idiopathic scoliosis by anterior correction
      and fusion surgery using dual-rod instrumentation: a minimum 12-year follow-up
      study.
AB  - BACKGROUND CONTEXT: Consensus regarding the optimal upper vertebra to be
      instrumented during surgical treatment of Lenke 5C thoracolumbar and lumbar
      adolescent idiopathic scoliosis (AIS) remains limited. PURPOSE: This study aimed
      to assess whether a short fusion strategy is appropriate for correction of a
      Lenke 5C AIS curve by anterior correction and fusion surgery using dual-rod
      instrumentation. STUDY DESIGN: This study design used retrospective comparative
      analysis of a prospectively collected, consecutive, non-randomized series of
      patients at a single institution. PATIENT SAMPLE: Thirty consecutive patients
      with Lenke 5C AIS treated with anterior correction and fusion surgery using dual
      rod instrumentation were included. OUTCOME MEASURES: Patient demographics,
      radiographic measurements, and Scoliosis Research Society-22 questionnaire (SRS
      22) scores were the outcome measures for this study. METHODS: Thirty patients
      were treated surgically for AIS with a Lenke 5C curve (mean age, 14.4 years [11
      19 years)]) and followed up for a mean period of 17.2 years (12-23 years).
      Radiographical parameters and clinical outcomes were compared between patients
      treatment with the end vertebra (EV) instrumented (n=14) and those treated by
      short fusion (S group) with instrumentation starting at the vertebra one level
      caudal to the EV (n=16 patients). There were no study-specific biases related to
      conflicts of interest. RESULTS: In the EV group, a mean preoperative Cobb angle
      of 56 degrees  was corrected to 5 degrees  after surgery and to 8 degrees  at the
      final follow-up. In the S group, a mean preoperative Cobb angle of 55 degrees 
      was corrected to 10 degrees  after surgery and 14 degrees  at the final follow
      up. The mean correction rate at the final follow-up was significantly lower in
      the S group (74%) than in the EV group (86%; p=.020). The coronal and sagittal
      balance, thoracic kyphosis, lumbar lordosis, and clinical outcomes evaluated
      using SRS-22 did not differ between the two groups. CONCLUSIONS: The short fusion
      strategy, which involves instrumentation of the vertebra one level caudal to the
      upper EV, can be considered as an alternative to the conventional strategy, which
      includes instrumentation of the upper EV, for treating Lenke 5C curves via
      anterior spinal fusion.

PMID- 26291400
TI  - A cost-utility analysis of sacral anterior root stimulation (SARS) compared with
      medical treatment in patients with complete spinal cord injury with a neurogenic
      bladder.
AB  - BACKGROUND CONTEXT: Sacral anterior root stimulation (SARS) and posterior sacral
      rhizotomy restores the ability to urinate on demand with low residual volumes,
      which is a key for preventing urinary complications that account for 10% of the
      causes of death in patients with spinal cord injury with a neurogenic bladder.
      Nevertheless, comparative cost-effectiveness results on a long time horizon are
      lacking to adequately inform decisions of reimbursement. PURPOSE: This study
      aimed to estimate the long-term cost-utility of SARS using the Finetech-Brindley
      device compared with medical treatment (anticholinergics+catheterization). STUDY
      DESIGN/SETTINGS: The following study design is used for the paper: Markov model
      elaborated with a 10-year time horizon; with four irreversible states: (1)
      initial treatment, (2) year 1 of surgery for urinary complication, (3) year >1 of
      surgery for urinary complication, and (4) death; and reversible states: urinary
      calculi; Finetech-Brindley device failures. PATIENT SAMPLE: The sample consisted
      of theoretical cohorts of patients with a complete spinal cord lesion since >=1
      year, and a neurogenic bladder. OUTCOME MEASURES: Effectiveness was expressed as
      quality adjusted life years (QALYs). Costs were valued in EUR 2013 in the
      perspective of the French health system. METHODS: A systematic review and meta
      analyses were performed to estimate transition probabilities and QALYs. Costs
      were estimated from the literature, and through simulations using the 2013 French
      prospective payment system classification. Probabilistic analyses were conducted
      to handle parameter uncertainty. RESULTS: In the base case analysis (2.5%
      discount rate), the cost-utility ratio was 12,710 EUR per QALY gained. At a
      threshold of 30,000 EUR per QALY the probability of SARS being cost-effective
      compared with medical treatment was 60%. If the French Healthcare System
      reimbursed SARS for 80 patients per year during 10 years (anticipated target
      population), the expected incremental net health benefit would be 174 QALYs, and
      the expected value of perfect information (EVPI) would be 4.735 million EUR. The
      highest partial EVPI is reached for utility values and costs (1.3-1.6 million
      EUR). CONCLUSIONS: Our model shows that SARS using Finetech-Brindley device
      offers the most important benefit and should be considered cost-effective at a
      cost-effectiveness threshold of 30,000 EUR per QALY. Despite a high uncertainty,
      EVPI and partial EVPI may indicate that further research would not be profitable
      to inform decision-making.

PMID- 26291401
TI  - Reliability of a new method for measuring coronal trunk imbalance, the axis-line
      angle technique.
AB  - BACKGROUND CONTEXT: Accurate determination of the extent of trunk imbalance in
      the coronal plane plays a key role in an evaluation of patients with trunk
      imbalance, such as patients with adolescent idiopathic scoliosis. An established,
      widely used practice in evaluating trunk imbalance is to drop a plumb line from
      the C7 vertebra to a key reference axis, the central sacral vertical line (CSVL)
      in full-spine standing anterioposterior radiographs, and measuring the distance
      between them, the C7-CSVL. However, measuring the CSVL is subject to
      intraobserver differences, is error-prone, and is of poor reliability. Therefore,
      the development of a different way to measure trunk imbalance is needed. PURPOSE:
      This study aimed to describe a new method to measure coronal trunk imbalance, the
      axis-line-angle technique (ALAT), which measures the angle at the intersection
      between the C7 plumb line and an axis line drawn from the vertebral centroid of
      the C7 to the middle of the superior border of the symphysis pubis, and to
      compare the reliability of the ALAT with that of the C7-CSVL. STUDY
      DESIGN/SETTING: A prospective study at a university hospital was used. PATIENT
      SAMPLE: The patient sample consisted of sixty-nine consecutively enrolled men and
      women patients, aged 10-18 years, who had trunk imbalance defined as C7-CSVL
      longer than 20 mm on computed full-spine standing anterioposterior radiographs.
      OUTCOME MEASURES: Data were analyzed to determine the correlation between C7-CSVL
      and ALAT measurements and to determine intraobserver and interobserver
      reliabilities. METHODS: Using a picture archiving and communication system, three
      radiologists independently evaluated trunk imbalance on the 69 computed
      radiographs by measuring the C7-CSVL and by measuring the angle determined by the
      ALAT. Data were analyzed to determine the correlations between the two measures
      of trunk imbalance, and to determine intraobserver and interobserver
      reliabilities of each of them. RESULTS: Overall results from the measurements by
      the C7-CSVL and the ALAT were significantly moderately correlated. Intraobserver
      assessments by measuring the C7-CSVL and by doing the ALAT failed to find any
      significant differences between the findings from the first and second
      assessments by the same radiologist. Interobserver assessments significantly
      differed between radiologists 1 and 2 for the first assessment measuring the C7
      CSVL, and between radiologists 2 and 3 for the second assessment measuring the C7
      CSVL. Interobserver assessments by doing the ALAT failed to find any significant
      differences among the three radiologists for either of the two assessments.
      CONCLUSIONS: Our results indicated that using the ALAT, which is simple and
      convenient, is of great value in measuring trunk imbalance. For measuring trunk
      imbalance, the ALAT has essential advantages compared with measuring the C7-CSVL.
      We encourage spine surgeons to consider using the ALAT in evaluating trunk
      imbalance.

PMID- 26291402
TI  - Endocannabinoids, through opioids and prostaglandins, contribute to fever induced
      by key pyrogenic mediators.
AB  - This study aims to explore the contribution of endocannabinoids on the cascade of
      mediators involved in LPS-induced fever and to verify the participation of
      prostaglandins and endogenous opioids in fever induced by anandamide (AEA). Body
      temperature (Tc) of male Wistar rats was recorded over 6h, using a thermistor
      probe. Cerebrospinal fluid concentration of PGE2 and beta-endorphin were measured
      by ELISA after the administration of AEA. Intracerebroventricular administration
      of the CB1 receptor antagonist AM251 (5MUg, i.c.v.), reduced the fever induced by
      IL-1beta (3ng, i.c.v.), TNF-alpha (250ng, i.c.v.), IL-6 (300ng, i.c.v.),
      corticotrophin release factor (CRH; 2.5MUg, i.c.v.) and endothelin (ET)-1 (1pmol,
      i.c.v.), but not the fever induced by PGE2 (250ng, i.c.v.) or PGF2alpha (250ng,
      i.c.v.). Systemic administration of indomethacin (2mgkg(-1), i.p.) or celecoxib
      (5mgkg(-1), p.o.) reduced the fever induced by AEA (1MUg, i.c.v.), while naloxone
      (1mgkg(-1), s.c.) abolished it. The increases of PGE2 and beta-endorphin
      concentration in the CSF induced by AEA were abolished by the pretreatment of
      rats with AM251. These results suggest that endocannabinoids are intrinsically
      involved in the pyretic activity of cytokines (IL-1beta, TNF-alpha, IL-6), CRH
      and ET-1 but not the PGE2 or PGF2alpha induced fevers. However, anandamide via
      CB1 receptor activation induces fever that is dependent on the synthesis of
      prostaglandin and opioids. 

PMID- 26291403
TI  - Men and women differ in inflammatory and neuroendocrine responses to endotoxin
      but not in the severity of sickness symptoms.
AB  - Impaired mood and increased anxiety represent core symptoms of sickness behavior
      that are thought to be mediated by pro-inflammatory cytokines. Moreover,
      excessive inflammation seems to be implicated in the development of
      mood/affective disorders. Although women are known to mount stronger pro
      inflammatory responses during infections and are at higher risk to develop
      depressive and anxiety disorders compared to men, experimental studies on sex
      differences in sickness symptoms are scarce. Thus, the present study aimed at
      comparing physiological and psychological responses to endotoxin administration
      between men and women. Twenty-eight healthy volunteers (14 men, 14 women) were
      intravenously injected with a low dose (0.4 ng/kg) of lipopolysaccharide (LPS)
      and plasma concentrations of cytokines and neuroendocrine factors as well as
      negative state emotions were measured before and until six hours after LPS
      administration. Women exhibited a more profound pro-inflammatory response with
      significantly higher increases in tumor necrosis factor (TNF)-alpha and
      interleukin (IL)-6. In contrast, the LPS-induced increase in anti-inflammatory IL
      10 was significantly higher in men. The cytokine alterations were accompanied by
      changes in neuroendocrine factors known to be involved in inflammation
      regulation. Endotoxin injection induced a significant increase in noradrenaline,
      without evidence for sex differences. The LPS-induced increase in cortisol was
      significantly higher in woman, whereas changes in dehydroepiandrosterone were
      largely comparable. LPS administration also increased secretion of prolactin, but
      only in women. Despite these profound sex differences in inflammatory and
      neuroendocrine responses, men and women did not differ in endotoxin-induced
      alterations in mood and state anxiety or non-specific sickness symptoms. This
      suggests that compensatory mechanisms exist that counteract the more pronounced
      inflammatory response in women, preventing an exaggerated sickness response.
      Disturbance of these compensatory mechanisms by environmental factors such as
      stress may promote the development of affective disorders in women.

PMID- 26291404
TI  - Infectious diseases, IL6 -174G>C polymorphism, and human development.
AB  - Interleukin-6 (IL6) is a pro-inflammatory cytokine that is required for
      resistance against many pathogens. However, sustained IL6 activity can cause
      tissue damage in the periphery and brain. Previous studies have shown that
      populations in disease-endemic regions adapt by selecting the high-producing G
      allele at the -174G>C (rs1800795) polymorphism, while others have linked
      increased IL6 to cognitive impairments. The present study sought to determine
      whether up-regulation of IL6 by the G-allele at rs1800795 polymorphism in disease
      endemic regions was associated with increased cognitive deficits and corollary
      reductions in social, economic, and political development. We tested these
      hypotheses in a global sample of 189 nations with World Health Organization
      ratings for infectious diseases. We also included the Historical Pathogen
      Prevalence index, a measure of national average intelligence (IQ), and the United
      Nation Human Development Index (HDI) including per capita income, life
      expectancy, child mortality, and fertility rate. IL6 -174G>C allele frequencies
      were obtained from 171,168 individuals spanning 84 nations. The high-producing G
      allele frequency was positively correlated with infectious disease ranking
      (r=0.745, P<0.001) and negatively with IQ (r=-0.524, P<0.001) and HDI (r=-0.671,
      P<0.001). These robust findings suggest that in regions with a high pathogen
      burden the need for a strong IL6 response is accompanied by cognitive deficits
      and reduced HDI ranking. 

PMID- 26291406
TI  - The relative importance of relational and scientific characteristics of
      psychotherapy: Perceptions of community members vs. therapists.
AB  - Although client preferences are an integral component of evidence-based practice
      in psychology (American Psychological Association, 2006), relatively little
      research has examined what potential mental health consumers value in the
      psychotherapy they may receive. The present study was conducted to examine
      community members' preferences for the scientific and relational aspects of
      psychotherapy for different types of presenting problems, and how accurately
      therapists perceive these preferences. Community members (n = 200) were surveyed
      about the importance of scientific (e.g., demonstrated efficacy in clinical
      trials) and relational (e.g., therapist empathy) characteristics of psychotherapy
      both for anxiety disorders (e.g., obsessive-compulsive disorder) and disorder
      nonspecific issues (e.g., relationship difficulties). Therapists (n = 199)
      completed the same survey and responded how they expected the average mental
      health consumer would. Results showed that although community members valued
      relational characteristics significantly more than scientific characteristics,
      the gap between these two was large for disorder-nonspecific issues (d = 1.24)
      but small for anxiety disorders (d = .27). Community members rated scientific
      credibility as important across problem types. Therapists significantly
      underestimated the importance of scientific characteristics to community members,
      particularly in the treatment of disorder-nonspecific issues (d = .74).
      Therapists who valued research less in their own practice were more likely to
      underestimate the importance of scientific credibility to community members. The
      implications of the present findings for understanding the nature of client
      preferences in evidence-based psychological practice are discussed.

PMID- 26291405
TI  - Chronic restraint stress triggers dopaminergic and noradrenergic
      neurodegeneration: Possible role of chronic stress in the onset of Parkinson's
      disease.
AB  - Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss
      of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) and, to
      a lesser extent, in the noradrenergic neurons of the locus coeruleus (LC). Most
      cases of PD are idiopathic and sporadic and are believed to be the result of both
      environmental and genetic factors. Here, to the best of our knowledge, we report
      the first evidence that chronic restraint stress (8h/day, 5days/week)
      substantially reduces nigral DA and LC noradrenergic neuronal cell numbers in
      rats. Loss of DA neurons in the SNpc was evident after 2weeks of stress and
      progressed in a time-dependent manner, reaching up to 61% at 16weeks. This
      reduction was accompanied by robust microglial activation and oxidative stress
      and was marked by nitrotyrosine in the SNpc and LC of the midbrain. These results
      indicate that chronic stress triggers DA and noradrenergic neurodegeneration by
      increasing oxidative stress, and that activated microglia in the substantia nigra
      and LC may play an important role in modulating the neurotoxic effects of
      oxidative stress. Taken together, these data suggest that exposure to chronic
      stress triggers DA and noradrenergic neurodegeneration, which is a cause of PD. 

PMID- 26291407
TI  - Adeno-associated virus serotypes for gene therapeutics.
AB  - Gene transfer vectors based on adeno-associated virus (AAV) are showing exciting
      therapeutic promise in early phase clinical trials. The ability to cross-package
      the prototypic AAV2 vector genome into different capsids is a powerful way of
      conferring novel tropism and biology, with evolving capsid engineering
      technologies and directed evolution approaches further enhancing the utility and
      flexibility of these vectors. Novel properties of specific capsids show
      unpredictable species and cell-type specificity. Therefore, full realisation of
      the therapeutic potential of AAV vectors requires the development of more
      therapeutically predictive preclinical methods for evaluating capsid performance.
      This will strongly complement an iterative approach to the evaluation of capsid
      variants in the clinic and, should wherever possible, include the determination
      of gene transfer efficiencies. 

PMID- 26291409
TI  - Protein-specific imaging of posttranslational modifications.
AB  - Protein posttranslational modifications (PTMs) modulate protein function,
      trafficking, and interactions. Many PTMs ubiquitously occurs on hundreds and
      thousands of proteins, which makes cellular imaging of the PTM state of a
      specific protein like looking for a needle in a haystack. A proximity-enabled
      strategy, which exploits the spatial proximity between the PTM and the modified
      protein, has emerged as a valuable tool for protein-specific imaging of PTMs in
      single cells and tissue sections. The protein and the PTM are dually labeled with
      two distinct tags, which enable the generation of the nanometer proximity
      dependent fluorescent signals for visualization. Herein, we review recent
      advances in the methodological developments and the applications of the proximity
      enabled protein-specific imaging in studying phosphorylation, glycosylation, and
      lipidation. 

PMID- 26291408
TI  - Hydrophilic packaging of iron oxide nanoclusters for highly sensitive imaging.
AB  - Superparamagnetic iron oxide nanoparticles (SPIONs) are used as imaging probes to
      provide contrast in magnetic resonance images. Successful use of SPIONs in
      targeted applications greatly depends on their ability to generate contrast, even
      at low levels of accumulation, in the tissue of interest. In the present study,
      we report that SPION nanoclusters packaged to a controlled size by a
      hyperbranched polyglycerol (HPG) can target tissue defects and have a high
      relaxivity of 719 mM(-1) s(-1), which was close to their theoretical maximal
      limit. The resulting nanoclusters were able to identify regions of defective
      vasculature in an ischemic murine hindlimb using MRI with iron doses that were 5
      10 fold lower than those typically used in preclinical studies. Such high
      relaxivity was attributed to the molecular architecture of HPG, which mimics that
      of the water retentive polysaccharide, glycogen. The results of this study will
      be broadly useful in sensitive imaging applications. 

PMID- 26291410
TI  - Rethinking the Standard for Ductal Carcinoma In Situ Treatment.

PMID- 26291411
TI  - Untreated wheat straw: potential source for diverse cellulolytic enzyme secretion
      by Penicillium janthinellum EMS-UV-8 mutant.
AB  - Study describes the production of cellulases by Penicillium janthinellum EMS-UV-8
      using untreated wheat straw (WS), treated WS (acid, alkali, steam exploded,
      organo-solv) and pure cellulosic substrates (avicel, cellulose-II and
      carboxymethyl cellulose). Severely pretreated WS and cellulose-II produced more
      cellulolytic enzymes than untreated samples. XRD and FTIR analysis revels that
      the increase in the amorphous structure of pretreated WS/cellulose increases
      enzyme production. Enzyme samples prepared using different substrates were used
      for the hydrolysis of dilute acid treated wheat straw (DATWS), steam exploded
      wheat straw (SEWS) and avicel. The enzyme prepared using untreated WS gave more
      hydrolysis of DATWS and SEWS than the enzyme prepared using pretreated WS or pure
      cellulosic substrates. This revels that more diverse/potential enzymes were
      secreted by P. janthinellum EMS-UV-8 mutant using untreated WS. This study may
      contribute in production of efficient enzyme mixture/cocktail by single fungal
      strain for economic conversion of biomass to sugars.

PMID- 26291412
TI  - Adsorption of butanol vapor on active carbons with nitric acid hydrothermal
      modification.
AB  - Butanol can be produced from biomass via fermentation and used in vehicles.
      Unfortunately, butanol is toxic to the microbes, and this can slow fermentation
      rates and reduce butanol yields. Butanol can be efficiently removed from
      fermentation broth by gas stripping, thereby preventing its inhibitory effects.
      Original active carbon (AC) and AC samples modified by nitric acid hydrothermal
      modification were assessed for their ability to adsorb butanol vapor. The
      specific surface area and oxygen-containing functional groups of AC were tested
      before and after modification. The adsorption capacity of unmodified AC samples
      was the highest. Hydrothermal oxidation of AC with HNO3 increased the surface
      oxygen content, Brunauer-Emmett-Teller (BET) surface area, micropore, mesopore
      and total pore volume of AC. Although the pore structure and specific surface
      area were greatly improved after hydrothermal oxidization with 4M HNO3, the
      increased oxygen on the surface of AC decreased the dynamic adsorption capacity.

PMID- 26291413
TI  - Competitive adsorption of heavy metals by extracellular polymeric substances
      extracted from Klebsiella sp. J1.
AB  - The adsorption of Cu(2+) and Zn(2+) by extracellular polymeric substances (EPS)
      extracted from Klebsiella sp. J1 and competitive adsorption mechanism were
      investigated. Equilibrium adsorption capacities of Cu(2+) (1.77mMg(-1)) on
      Klebsiella sp. J1 EPS were higher than those of Zn(2+) (1.36mMg(-1)) in single
      systems. The competitive Langmuir and Langmuir-Freundlich isotherm models were
      proven to be effective in describing the experimental data of binary component
      system. The three dimensional sorption surfaces of binary component system
      demonstrated that the presence of Cu(2+) more significantly decreased the
      sorption of Zn(2+), but the sorption of Cu(2+) was not disturbed by the presence
      of Zn(2+). FTIR and EEM results revealed the adsorption sites of Cu(2+) entirely
      overlapped with those of Zn(2+). Cu(2+) and Zn(2+) showed competitive adsorption
      in binary systems, and Cu(2+) was preferentially adsorbed because of the stronger
      complexation ability of the protein-like substances in Klebsiella sp. J1 EPS.

PMID- 26291414
TI  - Researching Applicants Online in the Veterinary Program Admissions Process:
      Perceptions, Practices, and Implications for Curricular Change.
AB  - As the use of social media websites continues to grow among adults 18-34 years
      old, it is necessary to examine the consequences of online disclosure to the
      veterinary admissions processes and to consider the effects on the professional
      integrity of veterinary schools and on the e-professionalism of DVM graduates.
      Prior research has shown that employers, across all fields, routinely use
      information from social media sites to make hiring decisions. In veterinary
      medicine, a little over one-third of private practitioners reported using online
      information in the selection of new associates. However, professional academic
      programs appear to use online information less frequently in the selection
      processes. The current study examines the behaviors and attitudes of veterinary
      medical admissions committees toward the use of applicants' online information
      and profiles in their recruitment and selection process. An online survey was
      distributed to Associate Deans for Academic Affairs at all AAVMC-affiliated
      schools of veterinary medicine. A total of 21 schools completed the survey. The
      results showed that most veterinary schools do not currently use online research
      in their admissions process; however, most admissions committee members feel that
      using online social networking information to investigate applicants is an
      acceptable use of technology. Previous research has suggested that the majority
      of veterinary student applicants view this as an invasion of their privacy. Given
      this discordance, future educational efforts should focus on helping veterinary
      students determine what type of information is appropriate for posting online and
      how to use privacy settings to control their sharing behaviors. 

PMID- 26291415
TI  - A Dermatopathologist's Guide to Troubleshooting Immunohistochemistry--Part 2:
      Troubleshooting Immunohistochemical Tests in the Laboratory.
AB  - Unexpected staining patterns can arise from problems occurring in any of the
      steps required for IHC, some of which are discussed in part I of this CME series.
      Whether used to differentiate benign from malignant tumors, identify tumor
      subtypes, subtypes of hematopoietic malignancies, or identifying targets for
      therapy, the pathologist must be intimately familiar with the potential pitfalls
      that are inherent in the IHC methodology to troubleshoot problems in the
      laboratory, and more importantly, when interpreting immunohistochemical staining,
      to avoid pitfalls of false-positive or false-negative stains. 

PMID- 26291416
TI  - Histopathologic Variants of Cutaneous Squamous Cell Carcinoma In Situ With
      Analysis of Multicentric Subtypes: Possible Relationship to Human Papillomavirus.
AB  - Squamous cell carcinoma in situ (SCCIS) of the skin is relatively common. When
      the authors reviewed 3846 cutaneous SCCIS cases over an 18-month period, they
      found 6 distinct histopathologic subtypes of SCCIS, 5 of which demonstrated
      multicentric variants. Multicentric variants of SCCIS were noted on nongenital
      and nonmucosal skin. All of the multicentric cases that were studied with p16
      immunohistochemistry were positive in the tumor cells, suggesting a possible role
      of human papillomavirus in tumorigenesis. The authors believe that human
      papillomavirus likely plays a part in the development of these multicentric
      cutaneous SCCIS. 

PMID- 26291417
TI  - Usefulness of Random Skin Biopsy as a Diagnostic Tool of Intravascular Lymphoma
      Presenting With Fever of Unknown Origin.
AB  - BACKGROUND: Intravascular B-cell lymphoma (IVBCL) is a rare type of extranodal
      lymphoma in which the lymphoma proliferates within vascular lumen. One of the
      most common presenting symptoms is prolonged fever. Although examination of a
      random skin biopsy from healthy-appearing skin in patients with suspected
      intravascular lymphoma has been reported to be useful, the sensitivity of this
      method for diagnosis is still unknown. OBJECTIVE: To evaluate the usefulness of a
      random skin biopsy in the diagnosis of intravascular lymphoma in the patient
      presenting with fever of unknown origin. MATERIALS AND METHODS: All cases that we
      performed random skin biopsy were retrospectively reviewed from March 2007 to
      June 2012 in Ramathibodi Hospital. The incisional biopsy technique was performed
      in 3 separate locations including 2 specimens from both upper thighs and 1
      specimen from the abdomen. RESULTS: Of the 24 cases that were consulted to
      dermatologist for random skin biopsy, 3 cases (13%) were diagnosed of
      intravascular lymphoma and all presented with prolong fever, weight loss, and
      remarkable deterioration in Eastern Cooperative Oncology Group (ECOG) performance
      status (ECOG score) > 2. Interestingly, 2 cases (8%) were diagnosed with
      cytophagic histiocytic panniculitis from normal-appearing skin and subsequently
      investigated, which leads to the diagnosed of T-cell lymphoma. CONCLUSIONS: In an
      elderly patient with fever of unknown origin and/or weight loss with no evident
      of skin lesion, markedly elevated lactate dehydrogenase, remarkable deterioration
      in ECOG performance status who suspected IVBCL should be consider to perform
      incisional random skin biopsy at least 3 specimens from both thighs and abdomen
      to achieve a high sensitivity. We propose that this technique may serve as an
      important diagnostic tool to obtain the diagnosis of IVBCL. In summary, 5 of 24
      (21%) positive results from random skin biopsy helped diagnoses of lymphoma.

PMID- 26291418
TI  - Lymphocytic Arteritis in Epstein-Barr Virus Vulvar Ulceration (Lipschutz
      Disease): A Report of 7 Cases.
AB  - Epstein-Barr virus (EBV) infection can rarely present as painful genital ulcers,
      mostly in young female adolescents. Typically diagnosed by clinical findings, EBV
      vulvar ulceration (EBVVU) is rarely biopsied. Herein, the authors report the
      histopathology in 8 biopsies from 7 EBVVU patients, all serologically confirmed
      for acute (4/7) or reactivated-chronic (3/7) EBV infection. The 7 women all
      presented with 1 or more painful, punched-out vulvar ulcers. Only patients with
      acute EBV infection showed other clinical findings: fever and/or atypical
      lymphocytosis affected 75% (3/4); lymphadenopathy in 50%; and malaise/fatigue,
      dysuria and/or hepatomegaly in 25%. All reactivated-chronic EBVVU had a solitary
      ulcer, and 2 had history of a similar episode of vulvar ulceration (aphthosis).
      Histopathologically, lymphocytic arteritis was identified in 88% (7/8); a
      submucosal scar was found in the eighth specimen. Other histopathologies included
      venulitis (62%), endarteritis obliterans (38%), thrombosis (25%), neutrophilic
      sebaceous adenitis (25%), and mucosal lymphoid hyperplasia (12%). Dense
      angiocentric CD3 CD4 T-cell lymphocyte-predominant infiltrates were found,
      regionally or diffusely. In 2 specimens, neutrophils compromised half of the
      infiltrate. Minor components of CD8, CD20, and CD30 lymphocytes, CD123
      plasmacytoid monocytes, CD68 macrophages, and plasma cells were present. Small
      vessel endothelium and smooth muscle adjacent to the ulcers faintly expressed
      cytoplasmic EBV latent membrane protein-1 (LMP1). In situ hybridization for early
      EBV mRNA (EBER) identified rare solitary or scattered clustered positive
      lymphocytes in 38%. Polymerase chain reaction for EBV DNA was positive in one
      EBER positive biopsy. EBV infection has been documented in muscular vessel
      vasculitis. Based on the aforementioned, EBVVU appears to be the consequence of
      localized lymphocytic arteritis. 

PMID- 26291419
TI  - Vegetating Plaques on the Lips. Pyostomatitis vegetans.

PMID- 26291420
TI  - Papular Clear Cell Hyperplasia of the Eccrine Duct: A Precursor Lesion of Clear
      Cell Syringoma?
AB  - We report the case of a 77-year-old diabetic patient with asymptomatic papular
      eruption developed over a cutaneous scar after the resection of a squamous cell
      carcinoma. Histological examination revealed a clear cell proliferation involving
      the secretory portion of the eccrine glands. This entity has been previously
      named as papular clear cell hyperplasia of the eccrine duct. This clear cell
      change might be caused by glycogen deposition because of diabetes. We postulate
      that papular clear cell hyperplasia could be a precursor lesion of clear cell
      syringoma. 

PMID- 26291421
TI  - Juvenile Spring Eruption: A Variant of Perniosis?
AB  - Juvenile spring eruption (JSE) is a unique condition that typically affects the
      helices of the ears of boys and young men. The classical clinical picture of JSE
      includes the abrupt onset of lesions after spending time outdoors in the early
      spring. Because of the papulovesicular nature of the rash and the history of sun
      exposure, JSE is considered a variant of polymorphous light eruption. In addition
      to the term "juvenile spring eruption," this entity has also been described under
      other less common terms such as "perniosis juvenilis vernalis aurium" or "spring
      perniosis," which emphasizes the onset in the spring and the possible pathogenic
      role of cold weather. We present a case of likely JSE with histopathologic
      features more consistent with perniosis than polymorphous light eruption and
      present a review the literature. 

PMID- 26291423
TI  - Electrochemical electron paramagnetic resonance utilizing loop gap resonators and
      micro-electrochemical cells.
AB  - A miniaturised electrochemical cell design for Electron Paramagnetic Resonance
      (EPR) studies is reported. The cell incorporates a Loop Gap Resonator (LGR) for
      EPR investigation of electrochemically generated radicals in aqueous (and other
      large dielectric loss) samples and achieves accurate potential control for
      electrochemistry by using micro-wires as working electrodes. The electrochemical
      behaviour of the cell is analysed with COMSOL finite element models and the EPR
      sensitivity compared to a commercial TE011 cavity resonator using 4-hydroxy
      2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPOL) as a reference. The electrochemical
      EPR performance is demonstrated using the reduction of methyl viologen as a redox
      probe in both water and acetonitrile. The data reported herein suggest that sub
      micromolar concentrations of radical species can be detected in aqueous samples
      with accurate potential control, and that subtle solution processes coupled to
      electron transfer, such as comproportionation reactions, can be studied
      quantitatively using EPR. 

PMID- 26291424
TI  - Fatal Accelerated Cirrhosis after Imported HEV Genotype 4 Infection.

PMID- 26291425
TI  - A randomised controlled study comparing valethamate bromide and placebo in
      shortening the duration of active labour.
AB  - The aim of this study is to compare the efficacy and safety of valethamate
      bromide and placebo against placebo in shortening the duration of active labour.
      A prospective randomised trial of 158 low-risk women in spontaneous labour was
      conducted. After evaluation of the patients according to exclusion criteria 30
      women were given valethamate bromide (Group 1) and 32 women were given placebo
      (Group 2). Labour duration was the main outcome measure. The duration of the
      active phase after starting the treatment was similar in the two groups at 225
      and 219 min, respectively. However, differences were not significant between the
      2 groups. Side effects such as tachycardia, flushing of the face and dryness of
      mouth were noted with valethamate bromide administration. In conclusion,
      valethamate bromide did not significantly shortened the duration of active labour
      in nulliparous women with a singleton pregnancy at term. 

PMID- 26291426
TI  - Why babies - what Australian mothers say.
AB  - Earlier studies, mostly overseas, have explored the reasoning and thought
      processes underlying women's desires to conceive. A retrospective qualitative
      study was conducted to explore the motivations and anxieties of an Australian
      sample of women proceeding to a pregnancy and to explore their decision-making
      process. Twenty women over 18 years old who had one or more successful
      pregnancies and were recruited from a tertiary centre and private clinics,
      completed a questionnaire and a semi-structured interview. Thematic analysis was
      applied to the data. Multiple factors motivated women to proceed to a pregnancy
      and including influences arising from society or existing personal relationships,
      goals and desired experiences for parenthood and innate drives and reproductive
      related issues. The motivations of an urban Australian sample to proceed to a
      pregnancy differed little from studies elsewhere. This knowledge may assist in
      dealing with the concerns that underlie any pregnancy allowing for better
      obstetric management. 

PMID- 26291427
TI  - Acute haemothorax after ruptured ectopic pregnancy.

PMID- 26291428
TI  - Polyhydramnios associated with Prader-Willi syndrome.

PMID- 26291429
TI  - Effects of magnetic field gradients on the aggregation dynamics of colloidal
      magnetic nanoparticles.
AB  - We have used low-field (1)H nuclear-magnetic resonance (NMR) spectroscopy and
      molecular dynamics (MD) to investigate the aggregation dynamics of magnetic
      particles in ionic ferrofluids (IFFs) in the presence of magnetic field
      gradients. At the beginning of the experiments, the measured NMR spectra were
      broad and asymmetric, exhibiting two features attributed to different dynamical
      environments of water protons, depending on the local strength of the field
      gradients. Hence, the spatial redistribution of the magnetic particles in the
      ferrofluid caused by the presence of an external magnetic field in a time scale
      of minutes can be monitored in real time, following the changes in the features
      of the NMR spectra during a period of about an hour. As previously reported
      [Heinrich et al., Phys. Rev. Lett., 2011, 106, 208301], in the homogeneous
      magnetic field of a NMR spectrometer, the aggregation of the particles of the IFF
      proceeds in two stages. The first stage corresponds to the gradual aggregation of
      monomers prior to and during the formation of chain-like structures. The second
      stage proceeds after the chains have reached a critical average length, favoring
      lateral association of the strings into hexagonal zipped-chain superstructures or
      bundles. In this work, we focus on the influence of a strongly inhomogeneous
      magnetic field on the aforementioned aggregation dynamics. The main observation
      is that, as the sample is immersed in a certain magnetic field gradient and kept
      there for a time tauinh, magnetophoresis rapidly converts the ferrofluid into an
      aggregation state which finds its correspondence to a state on the evolution
      curve of the pristine sample in a homogeneous field. From the degree of
      aggregation reached at the time tauinh, the IFF sample just evolves thereafter in
      the homogeneous field of the NMR spectrometer in exactly the same way as the
      pristine sample. The final equilibrium state always consists of a colloidal
      suspension of zipped-chain bundles with the chain axes aligned along the magnetic
      field direction. 

PMID- 26291430
TI  - A novel electrochemical immunosensor for the quantitative detection of 5
      hydroxymethylcytosine in genomic DNA of breast cancer tissue.
AB  - A novel electrochemical immunosensor was fabricated for the quantitative
      detection of 5-hydroxymethylcytosine (5-hmC) in genomic DNA based on anti-5-hmC
      antibody, biotin functionalized phos-tag and avidin functionalized alkaline
      phosphatase. It is demonstrated that the levels of 5-hmC are dramatically reduced
      in human breast cancer tissue compared with those in normal tissue. 

PMID- 26291431
TI  - A comparison of two surgical approaches in functional neurosurgery:
      individualized versus conventional stereotactic frames.
AB  - OBJECT: The individualized Starfix(r) miniframe belongs to a new generation of
      stereotactic systems enabling high-precision electrode placement with
      considerably better time-efficiency in deep brain stimulation (DBS). We evaluated
      the usability and reliability of this novel technique in patients with idiopathic
      Parkinson's disease (IPD) and compared surgical and clinical results with those
      obtained in a historical group in which a conventional stereotactic frame was
      employed. METHODS: Sixty patients underwent surgery for implantation of DBS
      electrodes in the subthalamic nucleus. In 31 of them (group I) a conventional
      Zamorano-Dujovny frame was used and in 29 of them (group II) a Starfix(r)
      miniframe was used. Image fusion of preoperatively acquired 3D T1w and T2w 1.5 T
      MR-image series was used for the targeting procedure. Placement of the test
      electrodes and permanent electrodes corresponded to standard functional
      neurosurgery and included microelectrode recording and macrostimulation. Clinical
      (L-Dopa equivalent dose, United Parkinson's disease rating scale part III) and
      time for surgical electrode implantation were evaluated postoperatively in a 3-,
      6- and 12-month follow-up. RESULTS: Twelve months postoperatively, L-Dopa dose
      was significantly reduced from 685.19 to 205.88 mg/day and from 757.92 to 314.42
      mg/day in groups I and II, respectively. A comparable reduction of the LED could
      be observed 1 year after surgery. Motor function has improved in a significant
      and identical manner with 59% (group I) and 61% (group II). Besides clinical
      effects by stimulation therapy there was a significantly reduced surgery time
      required for electrode implantation using the Starfix(r) miniframe (group I:
      234.1 min, group II: 173.6 min; p < 0.001). CONCLUSIONS: Individualized
      miniframes such as the Starfix(r) miniframe allow implantation of DBS electrodes
      in IPD that is equally effective as conventional systems. The time efficiency
      achieved in surgery using of the Starfix(r) system helps to minimize patients'
      discomfort during DBS surgery.

PMID- 26291432
TI  - The cytotoxicity of gold nanoparticles is dispersity-dependent.
AB  - Nanoparticles are generally dispersed in electrolyte solutions for cell research.
      They may be aggregated and thus strongly influence the subsequent bio-effects.
      However, this has been often neglected in nanotoxicity research. In this paper,
      we selected gold nanoparticles as an example and investigated the role of
      dispersity in cytotoxicity. Our data indicated that the cytotoxicity of
      aggregated gold nanoparticles is significantly higher than well-dispersed ones.
      The dispersity-dependent cytotoxicity may be related to the increase of cellular
      endocytosis and reactive oxygen species. These results highlighted the importance
      of the dispersity of nanoparticles in nanotoxicity and nanobiotechnology fields. 

PMID- 26291434
TI  - Bringing a Battlefield Lesson Home.

PMID- 26291433
TI  - Optimized real-time monitoring of glutathione redox status in single pyramidal
      neurons in organotypic hippocampal slices during oxygen-glucose deprivation and
      reperfusion.
AB  - A redox-sensitive Grx1-roGFP2 fusion protein was introduced by transfection into
      single pyramidal neurons in the CA1 subfield of organotypic hippocampal slice
      cultures (OHSCs). We assessed changes in the GSH system in neuronal cytoplasm and
      mitochondria during oxygen-glucose deprivation and reperfusion (OGD/RP), an in
      vitro model of stroke. Pyramidal cells in a narrow range of depths below the
      surface of the OHSC were transfected by gene gun or single-cell electroporation
      with cyto- or mito-Grx1-roGFP2. To mimic the conditions of acute stroke, we
      developed an optimized superfusion system with the capability of rapid and
      reproducible exchange of the solution bathing the OHSCs. Measurements of pO2 as a
      function of tissue depth show that in the region containing the transfected
      cells, the pO2 is well-controlled. We also found that the pO2 changes on the same
      time scale as changes in intracranial pressure, cerebral blood flow, and pO2
      during acute stroke. Determining the reduction potential, EGSH, from the
      ratiometric fluorescence signal requires an absolute intensity measurement during
      calibration of the Grx1-roGFP2. Using the signal from cotransfected tdTomato as
      an internal standard during calibration improves quantitative measurements of
      Grx1-roGFP2 redox status and allows EGSH to be determined. EGSH becomes more
      reducing during OGD and more oxidizing during RP in mitochondria while changes in
      cytoplasm are not significant compared with controls. 

PMID- 26291436
TI  - Sunscreen slow down: The US FDA's sluggish approval of new sunscreens frustrates
      physicians, manufacturers, and consumers.

PMID- 26291435
TI  - The Effect of Dietary Intervention on Irritable Bowel Syndrome: A Systematic
      Review.
AB  - OBJECTIVES: Elimination diets have been used for many years to treat irritable
      bowel syndrome (IBS). These approaches had fallen out of favor until a recent
      resurgence, which was based on new randomized controlled trial (RCT) data that
      suggested it might be effective. The evidence for the efficacy of dietary
      therapies has not been evaluated systematically. We have therefore conducted a
      systematic review to examine this issue. METHODS: MEDLINE, EMBASE, and the
      Cochrane Controlled Trials Register were searched up to December 2013. Trials
      recruiting adults with IBS, which compared any form of dietary restriction or
      addition of an offending food group in patients already on a restricted diet vs.
      placebo, control therapy, or "usual management", were eligible. Dichotomous
      symptom data were pooled to obtain a relative risk of remaining symptomatic after
      therapy as well as the number needed to treat with a 95% confidence interval.
      RESULTS: We identified 17 RCTs involving 1,568 IBS patients that assessed
      elimination diets. Only three RCTs involving 230 patients met our eligibility
      criteria, all of which evaluated different approaches, and thus a meta-analysis
      could not be conducted. CONCLUSIONS: More evidence is needed before generally
      recommending elimination diets for IBS patients.

PMID- 26291437
TI  - HPV vaccine protects at multiple sites, even for some previously exposed.

PMID- 26291438
TI  - Father's age at birth of child may increase child's blood cancer risk.

PMID- 26291439
TI  - Erratum: Notable effects of angiotensin II receptor blocker, valsartan, on acute
      cardiotoxic changes after standard chemotherapy with cyclophosphamide,
      doxorubicin, vincristine, and prednisolone.

PMID- 26291442
TI  - Celebrating a Pearl Anniversary: Message From the President.

PMID- 26291441
TI  - Fluorescence tagging and inducible depletion of PD-L2-expressing B-1 B cells in
      vivo.
AB  - L2pB1 cells are a subpopulation of B-1a B cells that express programmed death
      ligand 2 (PD-L2) as their unique cell surface marker. In mice, about 50% of
      peritoneal B-1a cells are L2pB1 cells. The remaining B-1a cells are L2nB1 (PD-L2(
      ) ) B-1a cells. L2pB1 cells differ from L2nB1 cells in their immunoglobulin
      repertoire, expression of interleukin 10, and their capacity to phagocytose
      phosphatidylcholine. The physiological roles of L2pB1 cells have not been
      investigated owing to the lack of an animal model that allows for specific
      depletion of L2pB1 cells. Here, we report a mouse model that enables specific
      tracking and inducible depletion of L2pB1 cells in vivo. Our data show that
      depletion of L2pB1 cells significantly reduces serum anti-phosphorylcholine (PC)
      IgM levels and IL-10 expression in the peritoneal cavity. This animal model
      provides a tool for the study of the immune regulatory functions of L2pB1 cells
      in health and disease. 

PMID- 26291443
TI  - Toward a better understanding of dental appointment-keeping behavior.
AB  - OBJECTIVE: Broken appointments cause adverse outcomes in healthcare systems: They
      interrupt continuity of care, waste resources, affect workflow, and reduce
      population-wide access to care. A better understanding of dental appointment
      keeping behavior would support efforts toward designing novel interventions aimed
      at reducing rates of broken appointments. METHODS: The authors conducted a
      conceptual review of quantitative and qualitative research on dental appointment
      keeping in the United States. RESULTS: Research in this area is limited.
      Providers tend to use a blunt instrument to improve appointment-keeping: a system
      of reminder calls. There is evidence that patients with higher rates of broken
      dental appointments are the very ones who are most in need of care. Appointment
      keeping barriers are multifactorial and related to social issues. They can be
      described as falling into three overlapping categories: psychological barriers,
      structural barriers, and health literacy barriers. CONCLUSIONS: Appointment
      keeping interventions could simultaneously address social factors that exacerbate
      illness and improve workflow and finances. There arises an opportunity to design
      innovative patient-centered interventions tailored to particular barriers.

PMID- 26291444
TI  - Operationalising the capability approach as an outcome measure in public health:
      The development of the OCAP-18.
AB  - There is growing interest in operationalising the capability approach to measure
      quality of life. This paper reports the results of a research project undertaken
      in 2007 that sought to reduce and refine a longer survey in order to provide a
      summary measure of wellbeing and capability in the realm of public health. The
      reduction and refinement of the questionnaire took place across a number of
      stages, using both qualitative (five focus group discussions and 17 in-depth
      interviews) and quantitative (secondary data analysis, N = 1048 and primary data
      collection using postal surveys and interviews, N = 45) approaches. The
      questionnaire was reduced from its original 60+ questions to 24 questions
      (including demographic questions). Each of Nussbaum's ten Central Human
      Capabilities are measured using one (or more) of the 18 specific capability items
      which are included in the questionnaire (referred to as the OCAP-18). Analysis of
      the questionnaire responses (N = 198) found that respondents differed with
      respect to the levels of capabilities they reported, and that these capabilities
      appear to be sensitive to one's gender, age, income and deprivation decile. An
      index of capability, estimated by assuming equal weight for each capability
      question, found that the average level of capability amongst respondents was
      12.44 (range 3-17.75). This index was found to be highly correlated with a
      measure of health (EQ-5D) and wellbeing (global QoL), although some differences
      were apparent. This project operationalised the capability approach to produce an
      instrument to measure the effectiveness (and cost effectiveness) of public health
      interventions; the resulting OCAP-18 appears to be responsive and measure
      something supplementary to health and wellbeing, thus offers a promising addition
      to the current suite of outcome measures that are available. 

PMID- 26291445
TI  - The value of patient selection in demonstrating treatment effect in stroke
      recovery trials: lessons from the CHIMES study of MLC601 (NeuroAiD).
AB  - OBJECTIVE: The CHIMES Study compared MLC601 to placebo in patients with ischemic
      stroke of intermediate severity in the preceding 72 hours. We aimed to verify if
      patient selection based on two prognostic factors (ie, stroke severity and time
      to treatment) improves detection of a treatment effect with MLC601. METHODS:
      Analyses were performed using data from the CHIMES Study, an international,
      randomized, placebo-controlled, double-blind trial comparing MLC601 to placebo in
      patients with ischemic stroke of intermediate severity in the preceding 72 hours.
      Three subgroups, that is, onset to treatment time (OTT) >=48 hours; baseline
      National Institute of Health Stroke Scale (NIHSS) >=10; both OTT >=48 hours and
      baseline NIHSS >=10, were analyzed using modified Rankin Scale (mRS) <=1 and a
      composite endpoint of mRS <=1, Barthel Index >=95, and NIHSS <=1 at month 3.
      RESULTS: Placebo response rates were lower (ie, worse natural outcome) among
      subgroups with prognostic factors. Conversely, MLC601 treatment effects were
      significantly higher in the subgroups with prognostic factors than for the entire
      cohort, being highest among patients with both OTT >=48 hours and baseline NIHSS
      of 10 to 14: odds ratios of 2.18 (95% CI 1.02 to 4.65) for month 3 mRS <=1 and
      3.88 (95% CI 1.03 to 14.71) for the composite endpoint. CONCLUSIONS: Patients who
      have moderately severe strokes and longer OTT demonstrate better treatment
      effects with MLC601. These factors can guide patient selection in future trials.

PMID- 26291446
TI  - Impact of School Cycles and Environmental Forcing on the Timing of Pandemic
      Influenza Activity in Mexican States, May-December 2009.
AB  - While a relationship between environmental forcing and influenza transmission has
      been established in inter-pandemic seasons, the drivers of pandemic influenza
      remain debated. In particular, school effects may predominate in pandemic seasons
      marked by an atypical concentration of cases among children. For the 2009 A/H1N1
      pandemic, Mexico is a particularly interesting case study due to its broad
      geographic extent encompassing temperate and tropical regions, well-documented
      regional variation in the occurrence of pandemic outbreaks, and coincidence of
      several school breaks during the pandemic period. Here we fit a series of
      transmission models to daily laboratory-confirmed influenza data in 32 Mexican
      states using MCMC approaches, considering a meta-population framework or the
      absence of spatial coupling between states. We use these models to explore the
      effect of environmental, school-related and travel factors on the generation of
      spatially-heterogeneous pandemic waves. We find that the spatial structure of the
      pandemic is best understood by the interplay between regional differences in
      specific humidity (explaining the occurrence of pandemic activity towards the end
      of the school term in late May-June 2009 in more humid southeastern states),
      school vacations (preventing influenza transmission during July-August in all
      states), and regional differences in residual susceptibility (resulting in large
      outbreaks in early fall 2009 in central and northern Mexico that had yet to
      experience fully-developed outbreaks). Our results are in line with the concept
      that very high levels of specific humidity, as present during summer in
      southeastern Mexico, favor influenza transmission, and that school cycles are a
      strong determinant of pandemic wave timing. 

PMID- 26291447
TI  - Rapid, Precise, and Accurate Counts of Symbiodinium Cells Using the Guava Flow
      Cytometer, and a Comparison to Other Methods.
AB  - In studies of both the establishment and breakdown of cnidarian-dinoflagellate
      symbiosis, it is often necessary to determine the number of Symbiodinium cells
      relative to the quantity of host tissue. Ideally, the methods used should be
      rapid, precise, and accurate. In this study, we systematically evaluated methods
      for sample preparation and storage and the counting of algal cells using the
      hemocytometer, a custom image-analysis program for automated counting of the
      fluorescent algal cells, the Coulter Counter, or the Millipore Guava flow
      cytometer. We found that although other methods may have value in particular
      applications, for most purposes, the Guava flow cytometer provided by far the
      best combination of precision, accuracy, and efficient use of investigator time
      (due to the instrument's automated sample handling), while also allowing counts
      of algal numbers over a wide range and in small volumes of tissue homogenate. We
      also found that either of two assays of total homogenate protein provided a
      precise and seemingly accurate basis for normalization of algal counts to the
      total amount of holobiont tissue. 

PMID- 26291448
TI  - Long-term stability of sensitivity to intracortical microstimulation of
      somatosensory cortex.
AB  - OBJECTIVE: The dexterous manipulation of objects depends heavily on somatosensory
      signals from the limb. The development of anthropomorphic robotic arms and of
      algorithms to decode intended movements from neuronal signals has stimulated the
      need to restore somatosensation for use in upper-limb neuroprostheses. Without
      touch and proprioception, patients have difficulty controlling prosthetic limbs
      to a level that justifies the required invasive surgery. Intracortical
      microstimulation (ICMS) through chronically implanted electrode arrays has the
      potential to provide rich and intuitive sensory feedback. This approach to
      sensory restoration requires, however, that the evoked sensations remain stable
      over time. APPROACH: To investigate the stability of ICMS-evoked sensations, we
      measured the ability of non-human primates to detect ICMS over experimental
      sessions that spanned years. MAIN RESULTS: We found that the performance of the
      animals remained highly stable over time, even when they were tested with
      electrodes that had experienced extensive stimulation. SIGNIFICANCE: Given the
      stability of the sensations that it evokes, ICMS may thus be a viable approach
      for sensory restoration.

PMID- 26291449
TI  - Neural Basis of Psychological Growth following Adverse Experiences: A Resting
      State Functional MRI Study.
AB  - Over the past decade, research on the aftereffects of stressful or traumatic
      events has emphasized the negative outcomes from these experiences. However, the
      positive outcomes deriving from adversity are increasingly being examined, and
      such positive changes are described as posttraumatic growth (PTG). To investigate
      the relationship between basal whole-brain functional connectivity and PTG, we
      employed resting-state functional magnetic resonance imaging and analyzed the
      neural networks using independent component analysis in a sample of 33 healthy
      controls. Correlations were calculated between the network connectivity strength
      and the Posttraumatic Growth Inventory (PTGI) score. There were positive
      associations between the PTGI scores and brain activation in the rostral
      prefrontal cortex and superior parietal lobule (SPL) within the left central
      executive network (CEN) (respectively, r = 0.41, p < 0.001; r = 0.49, p < 0.001).
      Individuals with higher psychological growth following adverse experiences had
      stronger activation in prospective or working memory areas within the executive
      function network than did individuals with lower psychological growth (r = 0.40,
      p < 0.001). Moreover, we found that individuals with higher PTG demonstrated
      stronger connectivity between the SPL and supramarginal gyrus (SMG). The SMG is
      one of the brain regions associated with the ability to reason about the mental
      states of others, otherwise known as mentalizing. These findings suggest that
      individuals with higher psychological growth may have stronger functional
      connectivity between memory functions within the CEN and social functioning in
      the SMG, and that their better sociality may result from using more memory for
      mentalizing during their daily social interactions. 

PMID- 26291450
TI  - Riding the R Train into the Cell.

PMID- 26291451
TI  - Systematic Review and Meta-Analysis: Circulating miRNAs for Diagnosis of
      Hepatocellular Carcinoma.
AB  - Because early-stage hepatocellular carcinoma (HCC) is difficult to diagnose using
      the existing techniques, identifying better biomarkers would likely improve the
      patients' prognoses. We performed a systematic review and meta-analysis of
      published studies to appraise the utility of microRNAs (miRNAs) for the early
      diagnosis of HCC. Pertinent literature was collected from the Medline, Embase,
      and Chinese National Knowledge Infrastructure databases. We analyzed 50 studies
      that included 3423 cases of HCC, 2403 chronic hepatic disease (CH) patients, and
      1887 healthy controls in 16 articles. Summary receiver operating characteristic
      analyses of all miRNAs showed an area under the curve (AUC) of 0.82, with 75.8%
      sensitivity and 75.0% specificity in discriminating patients with HCC from
      healthy controls. miR-21 and miR-122 individually distinguished patients with HCC
      from healthy controls, with an AUC of 0.88 for miR-21 and 0.77 for miR-122. The
      sensitivity and specificity for miR-21 were 86.6% and 79.5%, respectively, those
      for miR-122 were 68.0% and 73.3%. We conclude that circulating miRNAs,
      particularly miR-21, and miR-122, are promising biomarkers for the early
      diagnosis of HCC.

PMID- 26291452
TI  - Sensitivity and Specificity of Double-Track Sign in the Detection of Transverse
      Sinus Stenosis: A Multicenter Retrospective Study.
AB  - BACKGROUND: Transverse sinus stenosis (TSS) is common among patients with
      cerebral venous sinus thrombosis. No previous studies have reported on double
      track sign detected on axial Gd-enhanced T1WI in TSS. This study aimed to
      determine the sensitivity and specificity of the double-track sign in the
      detection of TSS. METHODS: We retrospectively reviewed medical records of 383
      patients with transverse sinus thrombosis (TST) and 30 patients with normal
      transverse sinus from 5 participating hospitals in china from January 2008 to
      June 2014. 167 feasible transverse sinuses included in this study were
      categorized into TSS (n = 76), transverse sinus occlusion (TSO) (n = 52) and
      transverse sinus normal (TSN) groups (n = 39) according to imaging diagnosis on
      digital subtraction angiography (DSA) or magnetic resonance venography (MRV).
      Double-track sign on axial Gd-enhanced T1WI was compared among the three groups.
      Sensitivity and specificity of double-track sign in detection of TSS were
      calculated, with final imaging diagnosis of TSS on DSA or MRV as the reference
      standard. RESULTS: Of 383 patients with TST recruited over a 6.5-year period, 128
      patients were enrolled in the study, 255 patients were excluded because of
      insufficient clinical data, imaging finding and delay time, and 30 matched
      patients with normal transverse sinus were enrolled in the control group.
      Therefore, double-track sign assessment was conducted in 167 available transverse
      sinuses of 158 patients. Of the 76 sinuses in TSS group, 51 had double-track
      sign. Of the other 91 sinuses in TSO and TSN groups, 3 had a false-positive
      double-track sign. Thus, double-track sign on axial Gd-enhanced T1WI was 67.1%
      (95% CI 55.3-77.2) sensitive and 96.7% (95% CI 89.9-99.1) specific for detection
      of TSS. CONCLUSIONS: The double-track sign on axial Gd-enhanced T1WI is highly
      specific and moderate sensitive for detection of TSS. Nevertheless, it could be a
      direct sign and might provide an early clue for TSS.

PMID- 26291454
TI  - Association of Pretreatment Anemia with Pathological Response and Survival of
      Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: A Population-Based
      Study.
AB  - BACKGROUND: Anemia related to adjuvant chemotherapy might predict compromised
      survival in patients with breast cancer. The present population-based study was
      to investigate the correlation of pretreatment anemia with pathological response
      and long-term prognosis of breast cancer patients receiving neoadjuvant
      chemotherapy (NCT). METHODS: From 1999 to 2011, a total of 655 patients with
      operable or locally advanced breast cancer who underwent NCT before definitive
      surgery were reviewed. The patients were subdivided into anemic (baseline
      hemoglobin (Hb)<12.0 g/dL) and non-anemic (Hb>=12.0 g/dL) groups. Comparison was
      made between anemic and non-anemic groups concerning the rate of pathological
      complete response (pCR), relapse-free survival (RFS), overall survival (OS) and
      cancer-specific survival (CSS). Logistic and Cox regression models were utilized
      to determine the predictive value of pretreatment anemia in outcomes of patients
      undergoing NCT. RESULTS: 166 women (25.3%) were anemic before treatment. Patients
      in the anemic group were less likely to achieve pCR in NCT than their non-anemic
      counterparts (odds ratio (OR) 0.428, 95% confidence interval (CI) 0.198-0.927, p
      = 0.031). Patients with baseline anemia displayed inferior 10-year RFS (59.1% vs
      66.0%, p = 0.022 by log-rank), OS (75.3% vs 90.9%, p<0.001) and CSS (82.4% vs
      94.4%, p<0.001) compared with those without. After adjustment for confounders,
      pretreatment anemia was demonstrated to correlate with elevated risk of relapse
      (hazard ratio (HR) 1.453, 95% CI 1.077-1.962, p = 0.015), cancer-specific
      mortality (HR 2.961, 95% CI 1.679-5.222, p<0.001) and all-cause mortality (HR
      2.873, 95% CI 1.757-4.699, p<0.001). CONCLUSIONS: Pretreatment anemia was
      associated with worse pathological response to NCT as well as survival status in
      breast cancer. Further studies are warranted to identify optimal interventions
      and improve the prognosis of this subgroup.

PMID- 26291453
TI  - Role for Rab10 in Methamphetamine-Induced Behavior.
AB  - Lipid rafts are specialized, cholesterol-rich membrane compartments that help to
      organize transmembrane signaling by restricting or promoting interactions with
      subsets of the cellular proteome. The hypothesis driving this study was that
      identifying proteins whose relative abundance in rafts is altered by the abused
      psychostimulant methamphetamine would contribute to fully describing the pathways
      involved in acute and chronic effects of the drug. Using a detergent-free method
      for preparing rafts from rat brain striatal membranes, we identified density
      gradient fractions enriched in the raft protein flotillin but deficient in
      calnexin and the transferrin receptor, markers of non-raft membranes. Dopamine D1
      and D2-like receptor binding activity was highly enriched in the raft fractions,
      but pretreating rats with methamphetamine (2 mg/kg) once or repeatedly for 11
      days did not alter the distribution of the receptors. LC-MS analysis of the
      protein composition of raft fractions from rats treated once with methamphetamine
      or saline identified methamphetamine-induced changes in the relative abundance of
      23 raft proteins, including the monomeric GTP-binding protein Rab10, whose
      abundance in rafts was decreased 2.1-fold by acute methamphetamine treatment.
      Decreased raft localization was associated with a selective decrease in the
      abundance of Rab10 in a membrane fraction that includes synaptic vesicles and
      endosomes. Inhibiting Rab10 activity by pan-neuronal expression of a dominant
      negative Rab10 mutant in Drosophila melanogaster decreased methamphetamine
      induced activity and mortality and decreased caffeine-stimulated activity but not
      mortality, whereas inhibiting Rab10 activity selectively in cholinergic neurons
      had no effect. These results suggest that activation and redistribution of Rab10
      is critical for some of the behavioral effects of psychostimulants. 

PMID- 26291455
TI  - Estimating patient-specific soft-tissue properties in a TKA knee.
AB  - Surgical technique is one factor that has been identified as critical to success
      of total knee arthroplasty. Researchers have shown that computer simulations can
      aid in determining how decisions in the operating room generally affect post
      operative outcomes. However, to use simulations to make clinically relevant
      predictions about knee forces and motions for a specific total knee patient,
      patient-specific models are needed. This study introduces a methodology for
      estimating knee soft-tissue properties of an individual total knee patient. A
      custom surgical navigation system and stability device were used to measure the
      force-displacement relationship of the knee. Soft-tissue properties were
      estimated using a parameter optimization that matched simulated tibiofemoral
      kinematics with experimental tibiofemoral kinematics. Simulations using optimized
      ligament properties had an average root mean square error of 3.5 degrees  across
      all tests while simulations using generic ligament properties taken from
      literature had an average root mean square error of 8.4 degrees . Specimens
      showed large variability among ligament properties regardless of similarities in
      prosthetic component alignment and measured knee laxity. These results
      demonstrate the importance of soft-tissue properties in determining knee
      stability, and suggest that to make clinically relevant predictions of post
      operative knee motions and forces using computer simulations, patient-specific
      soft-tissue properties are needed.

PMID- 26291456
TI  - High Transmitter CD4+ T-Cell Count Shortly after the Time of Transmission in a
      Study of African Serodiscordant Couples.
AB  - BACKGROUND: 2013 WHO guidelines recommend starting ART at CD4+ T-cell counts
      <=500 cells/MUL. We present the T-cell counts from adult Africans with HIV
      shortly following transmission to their sexual partners. METHODS: HIV-discordant
      couples in Zambia, Uganda and Rwanda were followed prospectively and received
      couples counseling and condoms. HIV uninfected partners were tested for HIV at
      least quarterly and HIV-infected partners received HIV care and referral for ART
      per national guidelines. Upon diagnosis of incident HIV infection in the
      previously HIV-uninfected partner, a blood sample was collected from both
      partners to measure CD4+ T-cells and perform viral linkage. The estimated date of
      infection (EDI) of the incident case was calculated based on testing history. EDI
      was unknown for suspected transmitting partners. RESULTS: From 2006-2011, 4,705
      HIV-discordant couples were enrolled in this cohort, and 443 cases of incident
      HIV infection were documented. Virus linkage analysis was performed in 374
      transmission pairs, and 273 (73%) transmissions were linked genetically. CD4
      counts in the transmitting partner were measured a median of 56 days after EDI
      (mean:90.5, min:10, max:396). The median CD4 count was 339 cells/MUl (mean:386.4,
      min:15, max:1,434), and the proportion of partners with a CD4+ T-cell count above
      500/MUl was 25% (95% CI:21, 31). CONCLUSIONS: In our cohort of discordant
      couples, 73% of HIV transmissions occurred within the relationship, and the
      transmitter CD4+ T cell count shortly after the transmission event was frequently
      higher than the WHO 2013 ART-initiation guidelines.

PMID- 26291457
TI  - A Widening Gap? Changes in Multiple Lifestyle Risk Behaviours by Socioeconomic
      Status in New South Wales, Australia, 2002-2012.
AB  - BACKGROUND: Socioeconomic inequalities in health outcomes have increased over the
      past few decades in some countries. However, the trends in inequalities related
      to multiple health risk behaviours have been infrequently reported. In this
      study, we examined the trends in individual health risk behaviours and a summary
      lifestyle risk index in New South Wales, Australia, and whether the absolute and
      relative inequalities in risk behaviours by socioeconomic positions have changed
      over time. METHODS: Using data from the annual New South Wales Adult Population
      Health Survey during the period of 2002-2012, we examined four individual risk
      behaviours (smoking, higher than recommended alcohol consumption, insufficient
      fruit and vegetable intake, and insufficient physical activity) and a combined
      lifestyle risk indicator. Socioeconomic inequalities were assessed based on
      educational attainment and postal area-level index of relative socio-economic
      disadvantage (IRSD), and were presented as prevalence difference for absolute
      inequalities and prevalence ratio for relative inequalities. Trend tests and
      survey logistic regression models examined whether the degree of absolute and
      relative inequalities between the most and least disadvantaged subgroups have
      changed over time. RESULTS: The prevalence of all individual risk behaviours and
      the summary lifestyle risk indicator declined from 2002 to 2012. Particularly,
      the prevalence of physical inactivity and smoking decreased from 52.6% and 22% in
      2002 to 43.8% and 17.1% in 2012 (p for trend<0.001). However, a significant trend
      was observed for increasing absolute and relative inequalities in smoking,
      insufficient fruit and vegetable consumption, and the summary lifestyle risk
      indicator. CONCLUSIONS: The overall improvement in health behaviours in New South
      Wales, Australia, co-occurred with a widening socioeconomic gap. IMPLICATIONS:
      Governments should address health inequalities through risk factor surveillance
      and combined strategies of population-wide and targeted interventions.

PMID- 26291460
TI  - Medicine patent pool--pharma philanthropy or PR?
AB  - Merck recently signed an agreement with The Medicines Patent Pool (MPP) to
      license intellectual property relating to pediatric formulations of its integrase
      HIV drug, raltegravir (Ral) (the 'Agreement'). The Agreement is alleged to clear
      the way for cheaper formulations for use in developing and some middle income
      countries and allows for the development of novel pediatric formulations of Ral
      as well as novel combinations. Merck's license is royalty free and under the
      terms of the Agreement, manufacturers anywhere in the world who meet the quality
      assurance criteria, can manufacture and sell pediatric versions of the drug in
      the licensed countries under the agreed conditions without paying a royalty to
      Merck. The Agreement covers at least 92 countries and MPP reports that 98.1% of
      children with HIV in the developing world live in the included countries. The
      Agreement has been criticized as a public relations exercise. The article asks if
      the criticism is justified and explores several aspects of the Agreement in
      addressing the question. 

PMID- 26291458
TI  - Functional Divergence in the Role of N-Linked Glycosylation in Smoothened
      Signaling.
AB  - The G protein-coupled receptor (GPCR) Smoothened (Smo) is the requisite signal
      transducer of the evolutionarily conserved Hedgehog (Hh) pathway. Although
      aspects of Smo signaling are conserved from Drosophila to vertebrates,
      significant differences have evolved. These include changes in its active sub
      cellular localization, and the ability of vertebrate Smo to induce distinct G
      protein-dependent and independent signals in response to ligand. Whereas the
      canonical Smo signal to Gli transcriptional effectors occurs in a G protein
      independent manner, its non-canonical signal employs Galphai. Whether vertebrate
      Smo can selectively bias its signal between these routes is not yet known. N
      linked glycosylation is a post-translational modification that can influence GPCR
      trafficking, ligand responsiveness and signal output. Smo proteins in Drosophila
      and vertebrate systems harbor N-linked glycans, but their role in Smo signaling
      has not been established. Herein, we present a comprehensive analysis of
      Drosophila and murine Smo glycosylation that supports a functional divergence in
      the contribution of N-linked glycans to signaling. Of the seven predicted glycan
      acceptor sites in Drosophila Smo, one is essential. Loss of N-glycosylation at
      this site disrupted Smo trafficking and attenuated its signaling capability. In
      stark contrast, we found that all four predicted N-glycosylation sites on murine
      Smo were dispensable for proper trafficking, agonist binding and canonical signal
      induction. However, the under-glycosylated protein was compromised in its ability
      to induce a non-canonical signal through Galphai, providing for the first time
      evidence that Smo can bias its signal and that a post-translational modification
      can impact this process. As such, we postulate a profound shift in N-glycan
      function from affecting Smo ER exit in flies to influencing its signal output in
      mice. 

PMID- 26291459
TI  - Risk Factors and Outcomes for Postoperative Delirium after Major Surgery in
      Elderly Patients.
AB  - BACKGROUND: Early identification of patients at risk for delirium is important,
      since adequate well timed interventions could prevent occurrence of delirium and
      related detrimental outcomes. The aim of this study is to evaluate prognostic
      factors for delirium, including factors describing frailty, in elderly patients
      undergoing major surgery. METHODS: We included patients of 65 years and older,
      who underwent elective surgery from March 2013 to November 2014. Patients had
      surgery for Abdominal Aortic Aneurysm (AAA) or colorectal cancer. Delirium was
      scored prospectively using the Delirium Observation Screening Scale. Pre- and
      peri-operative predictors of delirium were analyzed using regression analysis.
      Outcomes after delirium included adverse events, length of hospital stay,
      discharge destination and mortality. RESULTS: We included 232 patients. 51 (22%)
      underwent surgery for AAA and 181 (78%) for colorectal cancer. Postoperative
      delirium occurred in 35 patients (15%). Predictors of postoperative delirium
      included: delirium in medical history (Odds Ratio 12 [95% Confidence Interval 2.7
      50]), advancing age (Odds Ratio 2.0 [95% Confidence Interval 1.1-3.8]) per 10
      years, and ASA-score >=3 (Odds Ratio 2.6 [95% Confidence Interval 1.1-5.9]).
      Occurrence of delirium was related to an increase in adverse events, length of
      hospital stay and mortality. CONCLUSION: Postoperative delirium is a frequent
      complication after major surgery in elderly patients and is related to an
      increase in adverse events, length of hospital stay, and mortality. A delirium in
      the medical history, advanced age, and ASA-score may assist in defining patients
      at increased risk for delirium. Further attention to prevention of delirium is
      essential in elderly patients undergoing major surgery.

PMID- 26291461
TI  - BCRP/ABCG2 inhibitors: a patent review (2009-present).
AB  - INTRODUCTION: BCRP/ABCG2 is a polyspecific ATP binding cassette transporter
      involved in multidrug resistance of tumors. Compared with P-glycoprotein/ABCB1
      only a few inhibitors are known. AREAS COVERED: Identification of ABCG2
      inhibitors in compound libraries and efforts made to develop new ABCG2 inhibitors
      are discussed in the review. Additionally, development of new test systems for
      testing ABCG2 activity and medical applications of ABCG2 inhibitors and
      activators are reviewed. EXPERT OPINION: ABCG2 is highly expressed in side
      population cells, which possess stem cell properties and are resistant to
      chemotherapy and radiotherapy. These cells are thought to lead to a relapse after
      chemotherapy. Therefore, inhibition of ABCG2 could have an additional benefit
      besides counteracting multidrug resistance. Among the new chemical entities, the
      bivalent flavonoids seem promising, as selective and broad spectrum inhibitors
      were found within this class of compounds. However, the available pharmacological
      data are rather preliminary.

PMID- 26291462
TI  - An evaluation of US patent 2015065565 (A1) for a new class of SGLT2 inhibitors
      for treatment 1 of type II diabetes mellitus.
AB  - INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a growing and serious global
      health problem. Pharmacological inhibition of the sodium-glucose cotransporter-2
      (SGLT2; SLC5A2) increases urinary glucose excretion, decreasing plasma glucose
      levels in an insulin-independent manner. Agents that inhibit SGLT2 have recently
      become available for clinical therapy of T2DM. AREAS COVERED: The patent claims a
      new class of SGLT2 inhibitors: derivatives of dioxa-bicyclo[3.2.1]octane-2,3,4
      triol (including ertugliflozin; PF-04971729). The invention describes the design,
      synthesis and pharmacological tests related to ertugliflozin, which could
      ultimately lead to efficacious therapy for T2DM alone or in combination with
      other anti-diabetic agents. EXPERT OPINION: Ertugliflozin is likely to be of
      great clinical significance in the near future. Continued analysis of
      ertugliflozin derivatives to now validate safe and efficacious treatment of T2DM
      in a larger number of clinical subjects over an extended period is needed to
      further support clinical utility. Identification, and discussion, of likely
      contra-indications is also needed.

PMID- 26291463
TI  - Synthesis and pharmacological activities of non-flavonoid chromones: a patent
      review (from 2005 to 2015).
AB  - INTRODUCTION: Chromones are one of the major classes of naturally occurring
      compounds. Their chemistry has been widely explored and extensively reviewed. The
      following review intends to give a broad overview of the patented chromones.
      Particular attention has been given to their synthesis, uses and applications in
      last 10 years. AREAS COVERED: The authors provide an overview of the recent
      scientific reports describing the obtaining and study of new chromones. The
      review emphasizes the rationale behind natural sources, synthesis, biological
      activities and structure-activity relationships of the new chromone derivatives.
      The article is based on the literature published from 2005 to 2015 related to the
      development of this family of compounds. The patents presented in this review
      have been collected from multiple electronic databases including SciFinder,
      Espacenet and Mendeley. EXPERT OPINION: Although a great number of chromones have
      been published in bibliographic sources in the last years, there is little
      innovation in the synthetic methodologies. Some natural sources and isolation
      techniques were described. Different pharmacological applications have also been
      claimed. Two of the most studied applications have been the use of these
      compounds as therapeutic agents for cancer and skin diseases. Some safety
      requirements need to be developed in order to find new chemical entities as new
      drugs.

PMID- 26291464
TI  - Copper-Catalyzed Asymmetric Conjugate Addition of Dimethylzinc to Acyl-N
      methylimidazole Michael Acceptors: a Powerful Synthetic Platform.
AB  - An efficient copper-catalyzed enantioselective conjugate addition of dimethylzinc
      to alpha,beta- and alpha,beta,gamma,delta-unsaturated 2-acyl-N-methylimidazoles
      has been achieved using a chiral bidentate hydroxyalkyl-NHC ligand. The reactions
      proceeded with both excellent regio- and enantioselectivity (14 examples, 87-95 %
      ee) to afford the desired 1,4-adducts, which were easily transformed to the
      corresponding aldehydes, esters, and ketones. Subsequently, this powerful
      methodology was therefore successfully applied in the synthesis of natural
      products. Furthermore, an iterative process was also disclosed leading to highly
      desirable 1,3-desoxypropionate skeletons (up to 94 % d.e.).

PMID- 26291465
TI  - Frequent ED utilizers: A case management program to address patient needs.

PMID- 26291466
TI  - Insights into the gold-catalyzed propargyl ester rearrangement/tandem cyclization
      sequence: radical versus gold catalysis-Myers-Saito- versus Schmittel-type
      cyclization.
AB  - A detailed study of the gold-catalyzed tandem 1,3-carboxy migration/allene-enyne
      cycloisomerization was undertaken. It was found that after the initial allene
      formation the selectivity of the reaction is strongly influenced by the
      polarization of the remaining alkyne. Depending on the substitution pattern of
      the starting diynes, either a Schmittel- or a Myers-Saito-type cyclization was
      triggered. The 6-endo-dig Myers-Saito-type cyclization gave access to
      benzo[b]fluorenes, while the Schmittel pathway (5-exo-dig) delivered
      benzofulvenes as final products. In special cases a yet unknown pathway was
      opened by the ambiphilic nature of the allene moiety. In these cases completely
      different products were obtained by the nucleophilic attack of the alkyne moiety
      onto the allene that can also act as an electrophile. Mechanistic studies
      revealed that diradical pathways can be ruled out for this type of tandem
      cyclization reactions and it is shown that both steps of the reaction cascade are
      catalyzed by the gold complex. 

PMID- 26291467
TI  - Scaling behavior of topologically constrained polymer rings in a melt.
AB  - Large scale molecular dynamics simulations on graphic processing units (GPUs) are
      employed to study the scaling behavior of ring polymers with various topological
      constraints in melts. Typical sizes of rings containing 3(1), 5(1) knots and
      catenanes made up of two unknotted rings scale like N(1/3) in the limit of large
      ring sizes N. This is consistent with the crumpled globule model and similar
      findings for unknotted rings. For small ring lengths knots occupy a significant
      fraction of the ring. The scaling of typical ring sizes for small N thus depends
      on the particular knot type and the exponent is generally larger than 0.4.

PMID- 26291468
TI  - Aortic Wall Injury Related to Endovascular Therapy for Aortic Coarctation.
AB  - Aortic wall complications can occur in unrepaired aortic coarctation (CoA) and
      after surgical repair or endovascular treatment. This review summarizes the
      available literature and current understanding of aortic wall injury (AWI)
      surrounding the management of CoA, focusing specifically on acute and follow-up
      AWI after endovascular treatment. There have been 23 reported cases of aortic
      rupture after endovascular treatment for CoA, including angioplasty alone, bare
      metal stenting, and primary covered stent therapy. Even if these published cases
      represent only a minority of ruptures that have actually occurred, the incidence
      is substantially <1%. The incidence of acute aneurysm formation was 0% to 13%
      after angioplasty, 0% to 5% after bare metal stent placement, and <1% after
      covered stent placement. The reported incidence and natural history of both acute
      and new AWI during follow-up after endovascular therapy for CoA varies
      considerably, likely secondary to ascertainment and reporting biases and
      inconsistent definitions. Although important AWI after endovascular treatment of
      CoA seems to be declining in frequency with increasing experience and improving
      technology, it remains one of the most important potential adverse outcomes. Long
      term surveillance for new AWI and monitoring of existing AWI is mandatory, with
      institution of appropriate treatment when necessary. A central research focus in
      this population should be determination of the appropriate treatment for both
      native and recurrent CoA across various ages with regard to limiting recurrent
      CoA and preventing associated aortic wall complications, in addition to
      determining the appropriate treatment of various AWI. Consistent definitions and
      reporting are necessary to truly understand the incidence of, risk factors for,
      and measures protective against AWI after angioplasty or stent implantation for
      CoA. 

PMID- 26291469
TI  - Randomness of Dengue Outbreaks on the Equator.
AB  - A simple mathematical model without seasonality indicated that the apparently
      chaotic dengue epidemics in Singapore have characteristics similar to epidemics
      resulting from chance. Randomness as a sufficient condition for patterns of
      dengue epidemics in equatorial regions calls into question existing explanations
      for dengue outbreaks there. 

PMID- 26291471
TI  - Pseudohalide (SCN(-))-Doped MAPbI3 Perovskites: A Few Surprises.
AB  - Pseudohalide thiocyanate anion (SCN(-)) has been used as a dopant in a
      methylammonium lead tri-iodide (MAPbI3) framework, aiming for its use as an
      absorber layer for photovoltaic applications. The substitution of SCN(-)
      pseudohalide anion, as verified using Fourier transform infrared (FT-IR)
      spectroscopy, results in a comprehensive effect on the optical properties of the
      original material. Photoluminescence measurements at room temperature reveal a
      significant enhancement in the emission quantum yield of MAPbI3-x(SCN)x as
      compared to MAPbI3, suggestive of suppression of nonradiative channels. This
      increased intensity is attributed to a highly edge specific emission from MAPbI3
      x(SCN)x microcrystals as revealed by photoluminescence microscopy. Fluoresence
      lifetime imaging measurements further established contrasting carrier
      recombination dynamics for grain boundaries and the bulk of the doped material.
      Spatially resolved emission spectroscopy on individual microcrystals of MAPbI3
      x(SCN)x reveals that the optical bandgap and density of states at various (local)
      nanodomains are also nonuniform. Surprisingly, several (local) emissive regions
      within MAPbI3-x(SCN)x microcrystals are found to be optically unstable under
      photoirradiation, and display unambiguous temporal intermittency in emission
      (blinking), which is extremely unusual and intriguing. We find diverse blinking
      behaviors for the undoped MAPbI3 crystals as well, which leads us to speculate
      that blinking may be a common phenomenon for most hybrid perovskite materials. 

PMID- 26291472
TI  - Stereoselective and Regiodivergent Allylic Suzuki-Miyaura Cross-Coupling of 2
      Ethoxydihydropyranyl Boronates: Synthesis and Confirmation of Absolute
      Stereochemistry of Diospongin B.
AB  - Oxygen-containing heterocycles such as pyrans are a common substructure present
      in a variety of natural products and pharmaceutical drugs. Highly functionalized
      4- and 6-aryl/heteroaryl dihydropyran derivatives are assembled by a highly
      stereoselective, ligand-controlled regiodivergent sp(3)-sp(2) Suzuki-Miyaura
      cross-coupling of a 2-ethoxy dihydropyranyl boronate derived from a catalytic
      enantioselective inverse-electron-demand oxa[4 + 2] cycloaddition. The scope and
      selectivity of this method were assessed along with an application to a concise
      total synthesis of the diarylheptanoid natural product diospongin B. 

PMID- 26291473
TI  - Characterization of oligocellulose synthesized by reverse phosphorolysis using
      different cellodextrin phosphorylases.
AB  - Much progress was made in the straightforward and eco-friendly enzymatic
      synthesis of shorter cellulose chains (oligocellulose). Here, we report the
      determination of a molar mass distribution of the oligocellulose synthesized from
      cellobiose (CB) and alpha-glucose 1-phosphate by reverse phosphorolysis, using
      enzymes cellodextrin phosphorylase from Clostridium stercorarium or Clostridium
      thermocellum as catalyst. The oligocellulose molar mass distribution was analyzed
      using three different methods: (1)H NMR spectroscopy, matrix assisted laser
      desorption/ionization-time-of-flight mass spectrometry (MALDI-ToF MS) and size
      exclusion chromatography (SEC). The molar mass distribution of the synthesized
      oligocellulose was only dependent on the concentration of cellobiose used in the
      reaction. Data obtained from MALDI-ToF MS and SEC were almost identical and
      showed that oligocellulose synthesized using 10 mM CB has an average degree of
      polymerization (DPn) of ~7, while a DPn of ~14 was achieved when 0.2 mM CB was
      used in the reaction. Because of solvent limitation in SEC analysis, MALDI-ToF MS
      was shown to be the technique of choice for accurate, easy and fast
      oligocellulose molar mass distribution determination. 

PMID- 26291470
TI  - Diffuse Lung Disease in Biopsied Children 2 to 18 Years of Age. Application of
      the chILD Classification Scheme.
AB  - RATIONALE: Children's Interstitial and Diffuse Lung Disease (chILD) is a
      heterogeneous group of disorders that is challenging to categorize. In previous
      study, a classification scheme was successfully applied to children 0 to 2 years
      of age who underwent lung biopsies for chILD. This classification scheme has not
      been evaluated in children 2 to 18 years of age. OBJECTIVES: This multicenter
      interdisciplinary study sought to describe the spectrum of biopsy-proven chILD in
      North America and to apply a previously reported classification scheme in
      children 2 to 18 years of age. Mortality and risk factors for mortality were also
      assessed. METHODS: Patients 2 to 18 years of age who underwent lung biopsies for
      diffuse lung disease from 12 North American institutions were included.
      Demographic and clinical data were collected and described. The lung biopsies
      were reviewed by pediatric lung pathologists with expertise in diffuse lung
      disease and were classified by the chILD classification scheme. Logistic
      regression was used to determine risk factors for mortality. MEASUREMENTS AND
      MAIN RESULTS: A total of 191 cases were included in the final analysis. Number of
      biopsies varied by center (5-49 biopsies; mean, 15.8) and by age (2-18 yr; mean,
      10.6 yr). The most common classification category in this cohort was Disorders of
      the Immunocompromised Host (40.8%), and the least common was Disorders of Infancy
      (4.7%). Immunocompromised patients suffered the highest mortality (52.8%).
      Additional associations with mortality included mechanical ventilation, worse
      clinical status at time of biopsy, tachypnea, hemoptysis, and crackles. Pulmonary
      hypertension was found to be a risk factor for mortality but only in the
      immunocompetent patients. CONCLUSIONS: In patients 2 to 18 years of age who
      underwent lung biopsies for diffuse lung disease, there were far fewer diagnoses
      prevalent in infancy and more overlap with adult diagnoses. Immunocompromised
      patients with diffuse lung disease who underwent lung biopsies had less than 50%
      survival at time of last follow-up.

PMID- 26291474
TI  - Azaphilone and Diphenyl Ether Derivatives from a Gorgonian-Derived Strain of the
      Fungus Penicillium pinophilum.
AB  - Three new azaphilone derivatives, pinophilins D-F (1-3), and one new diphenyl
      ether derivative, hydroxypenicillide (10), together with nine known compounds (4
      9, 11-13), were isolated from the gorgonian-derived fungus Penicillium pinophilum
      XS-20090E18. Their structures including absolute configurations were determined
      by spectroscopic data, chemical conversions, the ECD exciton chirality method,
      and ECD calculations. Compounds 10-13 exhibited inhibitory activity against the
      larval settlement of the barnacle Balanus amphitrite at nontoxic concentrations.
      Compounds 10 and 11 showed cytotoxicity against Hep-2, RD, and HeLa cell lines. 

PMID- 26291475
TI  - Tracking Pertussis and Evaluating Control Measures through Enhanced Pertussis
      Surveillance, Emerging Infections Program, United States.
AB  - Despite high coverage with pertussis-containing vaccines, pertussis remains
      endemic to the United States. There have been increases in reported cases in
      recent years, punctuated by striking epidemics and shifting epidemiology, both of
      which raise questions about current policies regarding its prevention and
      control. Limited data on pertussis reported through the National Notifiable
      Disease Surveillance System have proved insufficient to answer these questions.
      To address shortcomings of national pertussis data, the Emerging Infections
      Program at the US Centers for Disease Control and Prevention launched Enhanced
      Pertussis Surveillance (EPS), which is characterized by systematic case
      ascertainment, augmented data collection, and collection of Bordetella pertussis
      isolates. Data collected through EPS have been instrumental in understanding the
      rapidly evolving epidemiology and molecular epidemiology of pertussis and have
      contributed essential information regarding pertussis vaccines. EPS also serves
      as a platform for conducting critical and timely evaluations of pertussis
      prevention and control strategies, including targeting of vaccinations and
      antimicrobial prophylaxis. 

PMID- 26291476
TI  - Quantum Chemical Investigation of Light-Activated Spin State Change in Pyrene
      Coupled to Oxoverdazyl Radical Center.
AB  - Low-spin ground states and low-lying excited states of higher spin were
      investigated for four pyrene oxoverdazyl monoradicals 1-4 and eight pyrene
      dioxoverdazyl diradicals 5-12. The ground states for quartet and quintet spin
      symmetries that are in reality excited states were found in the region of 565-775
      nm above the respective electronic ground states. We calculated the "adiabatic"
      magnetic exchange coupling constant in the electronic ground state of each
      isolated biradical (5-12) by unrestricted density functional theory. A number of
      hybrid functionals such as B3LYP, PBE0, M06, and M06-2X were used. We also used
      range-separated functionals such as LC-omegaPBE and omegaB97XD to compare their
      effects on the coupling constant and the relative energy of the high-spin state.
      Molecular geometries were optimized for the doublet and quartet spin states of
      every monoradical (1-4), and the broken symmetry and triplet solutions were
      optimized for every biradical (5-12), by systematically using 6-311G, 6
      311G(d,p), and 6-311++G(d,p) basis sets with each functional. The geometry of
      each quintet diradical (5-12) was optimized using 6-311G basis set. B3LYP
      produced the best spin values. The excited state (quartet or quintet)-ground
      state energy difference (DeltaE) increases in the presence of para-phenylene
      connectors. These energy differences were predicted here. The nature of spin
      coupling and consequently the ground state spin agree with spin alternation rule
      and the calculated atomic spin population. The adiabatic coupling constants were
      predicted for the biradicals (5-12) in their electronic ground states. Electron
      paramagnetic resonance parameters were determined at 6-311++G** level for the
      ground state and the quartet state of 1 and compared with the available
      experimental data. Low-lying excited states were found for the radical center
      (oxoverdazyl), pyrene, molecule 1, and diradical 5 by time-dependent density
      functional theory (TDDFT) method using B3LYP hybrid, 6-311++G(d,p) basis set, and
      the molecular geometry in the electronic ground state. Data from these
      calculations were used to discuss possible mechanisms for the achievement of the
      high-spin (excited) states in 1 and 5 and to predict a similar outcome for
      radicals 2-4 and 6-12 upon excitation. A comprehensive mechanism for the first
      excitation is proposed here. In particular, we show that the initial excitation
      of 1 involves large contributions from mixed transitions between pyrene and
      oxoverdazyl moieties, whereas the initial excitation of 5 is basically that of
      only the pyrene fragment. Subsequent internal conversion and intersystem crossing
      are likely to lead to the high-spin states of lower energy. Sample spin-flip
      TDDFT calculations were also done to confirm the energetic location and
      composition of the quartet state of 1 and the quintet state of 5. 

PMID- 26291477
TI  - Polysaccharide-Protein Complexes in a Coarse-Grained Model.
AB  - We construct two variants of coarse-grained models of three hexaoses: one based
      on the centers of mass of the monomers and the other associated with the C4
      atoms. The latter is found to be better defined and more suitable for studying
      interactions with proteins described within alpha-C based models. We determine
      the corresponding effective stiffness constants through all-atom simulations and
      two statistical methods. One method is the Boltzmann inversion (BI) and the
      other, named energy-based (EB), involves direct monitoring of energies as a
      function of the variables that define the stiffness potentials. The two methods
      are generally consistent in their account of the stiffness. We find that the
      elastic constants differ between the hexaoses and are noticeably different from
      those determined for the crystalline cellulose Ibeta. The nonbonded couplings
      through hydrogen bonds between different sugar molecules are modeled by the
      Lennard-Jones potentials and are found to be stronger than the hydrogen bonds in
      proteins. We observe that the EB method agrees with other theoretical and
      experimental determinations of the nonbonded parameters much better than BI. We
      then consider the hexaose-Man5B catalytic complexes and determine the contact
      energies between their the C4-alpha-C atoms. These interactions are found to be
      stronger than the proteinic hydrogen bonds: about four times as strong for
      cellohexaose and two times for mannohexaose. The fluctuational dynamics of the
      coarse-grained complexes are found to be compatible with previous all-atom
      studies by Bernardi et al. 

PMID- 26291478
TI  - Validation of a Dosing Strategy for Cefazolin for Surgery Requiring
      Cardiopulmonary Bypass.
AB  - BACKGROUND: A prospective, single center, open-label study was conducted to
      determine if the standard practice for surgical prophylaxis, which includes
      standardized dosing of cefazolin, at the University of Maryland Medical Center
      (UMMC) is adequate for patients placed on bypass during cardiac surgery. METHODS:
      All patients were given the same standard dosing regimen regardless of weight:
      two grams of cefazolin administered within 1 h of incision, an additional one
      gram injected into the bypass circuit at the onset of bypass, and two grams every
      3 h after the initial dose. Cefazolin serum concentrations were collected
      immediately after incision, after the start of bypass, each hour of bypass, at
      the end of bypass and at sternal closure. RESULTS: Ten patients were consented
      and completed the study with an average age of 62 y, average weight of 84.7 kg
      and average cardiopulmonary bypass time of 116 min. The free serum concentrations
      of cefazolin stayed above the pre-defined inhibitory threshold of 16 mcg/mL
      throughout the procedure for 100% of participants. The mean total serum
      concentration in the blood throughout surgery was 160 mcg/mL. No patients were
      found to have surgical site infections using standard criteria and no adverse
      events were observed. CONCLUSIONS: For patients undergoing cardiac surgery with
      cardiopulmonary bypass, the UMMC dosing regimen surpassed targeted cefazolin
      concentrations during the entire surgical procedure for all patients regardless
      of weight or time on bypass.

PMID- 26291479
TI  - Retraction notice.

PMID- 26291480
TI  - A7RC peptide modified paclitaxel liposomes dually target breast cancer.
AB  - A7R peptide (ATWLPPR), a ligand of the NRP-1 receptor, regulates the
      intracellular signal transduction related to tumor vascularization and tumor
      growth. Here, we designed A7R-cysteine peptide (A7RC) surface modified paclitaxel
      liposomes (A7RC-LIPs) to achieve targeting delivery and inhibition of tumor
      growth and angiogenesis simultaneously. The cytotoxicity, inhibiting
      angiogenesis, and internalization of various liposomes by cells were assessed in
      vitro to confirm the influence of the peptide modification. The accumulations of
      A7RC-LIPs in various xenografts in mice were tracked to further identify the
      function of the peptide on the liposomes' surface. The results confirmed that
      A7RC peptides could enhance the uptake of vesicles by MDA-MB-231 cells, leading
      to stronger cytotoxicity in vitro and higher accumulation of vesicles in MDA-MB
      231 xenografts in vivo. In addition, A7RC peptides enhanced the inhibitory
      effects of LIPs on the HUVEC tubular formation on Matrigel. The A7RC-LIPs may be
      promising drug carriers for anticancer therapy. 

PMID- 26291481
TI  - Reckoning HIV/AIDS care: A longitudinal study of community home-based caregivers
      and clients in Swaziland.
AB  - The article is a descriptive case study of a community home-based care (CHBC)
      organisation in Swaziland that depicts the convergence of CHBC expansion with
      substantially improved health outcomes. Comprised of 993 care supporters who tend
      to 3 839 clients in 37 communities across southern Swaziland, Shiselweni Home
      based Care (SHBC) is illustrative of many resource-limited communities throughout
      Africa that have mobilised, at varying degrees of formality, to address the
      individual and household suffering associated with HIV/AIDS. To better understand
      the potential significance of global and national health policy/programming
      reliance on community health workers (task shifting), we analysed longitudinal
      data on both care supporter and client cohorts from 2008 to 2013. Most CHBC
      studies report data from only one cohort. Foremost, our analysis demonstrated a
      dramatic decline (71.4%) among SHBC clients in overall mortality from 32.2% to
      9.2% between 2008 and 2013. Although the study was not designed to establish
      statistical significance or causality between SHBC expansion and health impact,
      our findings detail a compelling convergence among CHBC, improved HIV health
      practices, and declines in client mortality. Our analysis indicated (1) the
      potential contributions of community health workers to individual and community
      wellbeing, (2) the challenges of task-shifting agendas, above all comprehensive
      support of community health workers/care supporters, and (3) the importance of
      data collection to monitor and strengthen the critical health services assigned
      to CHBC. Detailed study of CHBC operations and practices is helpful also for
      advancing government and donor HIV/AIDS strategies, especially with respect to
      health services decentralisation, in Swaziland and similarly profiled settings. 

PMID- 26291483
TI  - The importance of the p50 NF-kappaB subunit.

PMID- 26291482
TI  - The gut reaction to traumatic brain injury.
AB  - Traumatic brain injury (TBI) is a complex disorder that affects millions of
      people worldwide. The complexity of TBI partly stems from the fact that injuries
      to the brain instigate non-neurological injuries to other organs such as the
      intestine. Additionally, genetic variation is thought to play a large role in
      determining the nature and severity of non-neurological injuries. We recently
      reported that TBI in flies, as in humans, increases permeability of the
      intestinal epithelial barrier resulting in hyperglycemia and a higher risk of
      death. Furthermore, we demonstrated that genetic variation in flies is also
      pertinent to the complexity of non-neurological injuries following TBI. The goals
      of this review are to place our findings in the context of what is known about
      TBI-induced intestinal permeability from studies of TBI patients and rodent TBI
      models and to draw attention to how studies of the fly TBI model can provide
      unique insights that may facilitate diagnosis and treatment of TBI. 

PMID- 26291484
TI  - Superoxide anion-induced pain and inflammation depends on TNFalpha/TNFR1
      signaling in mice.
AB  - Inhibition of tumor necrosis factor-alpha (TNFalpha) and superoxide anion
      production reduces inflammation and pain. The present study investigated whether
      superoxide anion-induced pain depends on TNFalpha signaling and the role of
      superoxide anion in TNFalpha-induced hyperalgesia to clarify the interrelation
      between these two mediators in the context of pain. Intraplantar injection of a
      superoxide anion donor (potassium superoxide) induced mechanical hyperalgesia
      (0.5-5h after injection), neutrophil recruitment (myeloperoxidase activity), and
      overt pain-like behaviors (paw flinching, paw licking, and abdominal writhings)
      in wild-type mice. Tumor necrosis factor receptor 1 deficiency (TNFR1-/-) and
      treatment of wild-type mice with etanercept (a soluble TNFR2 receptor that
      inhibits TNFalpha actions) inhibited superoxide anion-induced pain-like
      behaviors. TNFR1(-/-) mice were also protected from superoxide anion donor
      induced oxidative stress, suggesting the role of this pathway in the maintenance
      of oxidative stress. Finally, we demonstrated that Apocynin (an NADPH oxidase
      inhibitor) or Tempol (a superoxide dismutase mimetic) treatment inhibited
      TNFalpha-induced paw mechanical hyperalgesia and neutrophil recruitment
      (myeloperoxidase activity). These results demonstrate that TNFalpha/TNFR1
      signaling is important in superoxide anion-triggered pain and that TNFalpha/TNFR1
      signaling amplifies the oxidative stress triggered by superoxide anion, which
      contributes to sustaining pain and inflammation. 

PMID- 26291485
TI  - The mechanisms of the effect of light finger touch on postural control.
AB  - The effect of light finger touch on reducing postural sway has been widely
      replicated; however, the mechanism of this effect has not been well understood.
      While the sensory hypothesis states that sensory stimuli available from light
      finger touch is used to automatically diminish postural sway, the suprapostural
      task hypothesis argues that posture is adjusted by the demand imposed by the
      precision requirements of light finger touch. The object of this study was to
      test the sensory and the suprapostural task hypotheses. Thirty-four adults kept
      quiet standing while lightly touching a stable plate using index finger with
      various touch forces (very light touch and light touch), and precision demands
      (low and high demand). Consistent with the sensory hypothesis, postural stability
      was significantly greater with light touch as compared to very light touch, as
      greater touch force results in greater amount of sensory stimuli. Also,
      consistent with the suprapostural task hypothesis, postural stability was
      significantly increased under high precision rather than low precision demand
      conditions. The current results indicated that both hypotheses were valid,
      suggesting that the sensory and the suprapostural task effects can coexist for
      adaptive control of postural sway, and in various scenarios, one is dominant over
      another. 

PMID- 26291486
TI  - A surviving patient after a cumulative dose of 250 g of cyclophosphamide.

PMID- 26291487
TI  - Different Craniofacial Characteristics Predict Upper Airway Collapsibility in
      Japanese-Brazilian and White Men.
AB  - BACKGROUND: OSA pathogenesis is complex and may vary according to ethnicity. The
      anatomic component predisposing to OSA is the result of the interaction between
      bony structure and upper airway soft tissues and can be assessed using passive
      critical closing pressure (Pcrit). We hypothesized that Japanese-Brazilians and
      whites present different predictors of upper airway collapsibility, suggesting
      different causal pathways to developing OSA in these two groups. METHODS: Male
      Japanese-Brazilians (n = 39) and whites (n = 39) matched for age and OSA severity
      were evaluated by full polysomnography, Pcrit, and upper airway and abdomen CT
      scans for determination of upper airway anatomy and abdominal fat, respectively.
      RESULTS: Pcrit was similar between the Japanese-Brazilians and the whites (-1.0
      +/- 3.3 cm H2O vs -0.4 +/- 3.1 cm H2O, P = .325). The Japanese-Brazilians
      presented smaller upper airway bony dimensions (cranial base, maxillary, and
      mandibular lengths), whereas the whites presented larger upper airway soft tissue
      (tongue length and volume) and a greater imbalance between tongue and mandible
      (tongue/mandibular volume ratio). The cranial base angle was associated with
      Pcrit only among the Japanese-Brazilians (r = -0.535, P < .01). The
      tongue/mandibular volume ratio was associated with Pcrit only among the whites (r
      = 0.460, P < .01). Obesity-related variables (visceral fat, BMI, and neck and
      waist circumferences) showed a similar correlation with Pcrit in the Japanese
      Brazilians and the whites. CONCLUSIONS: Japanese-Brazilians and whites present
      different predictors of upper airway collapsibility. Although craniofacial bony
      restriction influenced Pcrit only in the Japanese-Brazilians, an anatomic
      imbalance between tongue and mandible volume influenced Pcrit among the whites.
      These findings may have therapeutic implications regarding how to improve the
      anatomic predisposition to OSA across ethnicities.

PMID- 26291489
TI  - Considerations for randomizing 1 eye or 2 eyes.

PMID- 26291488
TI  - Comparison of satisfaction with care between two different models of HIV care
      delivery in St. Petersburg, Russia.
AB  - Prior to 2010, medical care for people living with HIV/AIDS was provided at an
      outpatient facility near the center of St. Petersburg. Since then, HIV specialty
      clinics have been established in more outlying regions of the city. The study
      examined the effect of this decentralization of HIV care on patients'
      satisfaction with care in clinics of St. Petersburg, Russia. We conducted a cross
      sectional study with 418 HIV-positive patients receiving care at the St.
      Petersburg AIDS Center or at District Infectious Disease Departments (centralized
      and decentralized models, respectively). Face-to-face interviews included
      questions about psychosocial characteristics, patient's satisfaction with care,
      and clinic-related patient experience. Abstraction of medical records provided
      information on patients' viral load. To compare centralized and decentralized
      models of care delivery, we performed bivariate and multivariate analysis.
      Clients of District Infectious Disease Departments spent less time in lines and
      traveling to reach the clinic, and they had stronger relationships with their
      doctor. The overall satisfaction with care was high, with 86% of the sample
      reporting high level of satisfaction. Nevertheless, satisfaction with care was
      strongly and positively associated with the decentralized model of care and
      Patient-Doctor Relationship Score. Patient experience elements such as waiting
      time, travel time, and number of services used were not significant factors
      related to satisfaction. Given the positive association of satisfaction with
      decentralized service delivery, it is worth exploring decentralization as one way
      of improving healthcare services for people living with HIV/AIDS. 

PMID- 26291490
TI  - Expression profiles and interaction suggest TBK1 can be regulated by Nrdp1 in
      response to immune stimulation in large yellow croaker Larimichthys crocea.
AB  - TBK1 has been extensively studied in mammals because of its important roles as a
      molecular bridge, linking the TLRs (TLR3 and TLR4) and RLRs signals to activate
      transcriptional factors IRF3 and IRF7 for IFN-I production. However, the
      information on molecular and functional characteristics of TBK1 in teleosts is
      limited. In this study, the molecular characterization and immune response of
      TBK1 in Larimichthys crocea (named as LcTBK1) as well as its interaction with
      Nrdp1 were investigated. Sequence analysis demonstrated that LcTBK1 included four
      functional motifs, the N-terminal protein kinase domain and ATP-binding site,
      middle ULD and C-terminal coiled-coil domain. The tissue expression profiles
      indicated that LcTBK1 gene was constitutively expressed in the twelve tissues
      examined, with high expression in brain. Temporal expression analysis showed that
      LcTBK1 mRNA was obviously increased in the liver after injection of LPS, Poly I:C
      and inactive Vibrio parahaemolyticus, however, declined at some time points in
      spleen and head-kidney. Furthermore, we found that LcTBK1 can interact with
      LcNrdp1, an E3 ubiquitin ligase that involved in immune response to Cryptocaryon
      irritans infection in L. crocea. The qPCR showed that LcNrdp1 was also
      significantly up-regulated in liver, down-regualted at some time points in spleen
      and head-kidney after LPS, Poly I:C and inactive V. parahaemolyticus injection,
      although the expression patterns of the two genes after the three treatments were
      different in change magnitude and up-regulation timespan. These results suggested
      that LcTBK1 was involved in L. crocea defense against the pathogen infection and
      can be regulated by Nrdp1 in PPRs signaling pathway of fishes.

PMID- 26291491
TI  - Recombinant sialidase NanA (rNanA) cleaves alpha2-3 linked sialic acid of host
      cell surface N-linked glycoprotein to promote Edwardsiella tarda infection.
AB  - Edwardsiella tarda is one of the major pathogenic bacteria affecting both marine
      and freshwater fish species. Sialidase NanA expressed endogenously in E. tarda is
      glycosidase removing sialic acids from glycoconjugates. Recently, the
      relationship of NanA sialidase activity to E. tarda infection has been reported,
      however, the mechanism with which sialidase NanA aids the pathogenicity of E.
      tarda remained unclear. Here, we comprehensively determined the biochemical
      properties of NanA towards various substrates in vitro to provide novel insights
      on the potential NanA target molecule at the host cell. GAKS cell pretreated with
      recombinant NanA showed increased susceptibility to E. tarda infection. Moreover,
      sialidase inhibitor treated E. tarda showed a significantly reduced ability to
      infect GAKS cells. These results indicate that NanA-induced desialylation of cell
      surface glycoconjugates is essential for the initial step of E. tarda infection.
      Among the natural substrates, NanA exhibited the highest activity towards 3
      sialyllactose, alpha2-3 linked sialic acid carrying sialoglycoconjugates.
      Supporting this finding, intact GAKS cell membrane exposed to recombinant NanA
      showed changes of glycoconjugates only in alpha2-3 sialo-linked glycoproteins,
      but not in glycolipids and alpha2-6 sialo-linked glycoproteins. Lectin staining
      of cell surface glycoprotein provided further evidence that alpha2-3 sialo
      linkage of the N-linked glycoproteins was the most plausible target of NanA
      sialidase. To confirm the significance of alpha2-3 sialo-linkage desialylation
      for E. tarda infection, HeLa cells which possessed lower amount of alpha2-3 sialo
      linkage glycoprotein were used for infection experiment along with GAKS cells. As
      a result, infection of HeLa cells by E. tarda was significantly reduced when
      compared to GAKS cells. Furthermore, E. tarda infection was significantly
      inhibited by mannose pretreatment suggesting that the bacterium potentially
      recognizes and binds to mannose or mannose containing chains following
      desialylation. Together, these results suggest that E. tarda may employ
      endogenous NanA to desialylate alpha2-3 glycoproteins on host cells, thus
      revealing one of the potential binding molecules during infection.

PMID- 26291492
TI  - A Gauss-Kronrod-Trapezoidal integration scheme for modeling biological tissues
      with continuous fiber distributions.
AB  - Fibrous biological tissues may be modeled using a continuous fiber distribution
      (CFD) to capture tension-compression nonlinearity, anisotropic fiber
      distributions, and load-induced anisotropy. The CFD framework requires spherical
      integration of weighted individual fiber responses, with fibers contributing to
      the stress response only when they are in tension. The common method for
      performing this integration employs the discretization of the unit sphere into a
      polyhedron with nearly uniform triangular faces (finite element integration or
      FEI scheme). Although FEI has proven to be more accurate and efficient than
      integration using spherical coordinates, it presents three major drawbacks:
      First, the number of elements on the unit sphere needed to achieve satisfactory
      accuracy becomes a significant computational cost in a finite element (FE)
      analysis. Second, fibers may not be in tension in some regions on the unit
      sphere, where the integration becomes a waste. Third, if tensed fiber bundles
      span a small region compared to the area of the elements on the sphere, a
      significant discretization error arises. This study presents an integration
      scheme specialized to the CFD framework, which significantly mitigates the first
      drawback of the FEI scheme, while eliminating the second and third completely.
      Here, integration is performed only over the regions of the unit sphere where
      fibers are in tension. Gauss-Kronrod quadrature is used across latitudes and the
      trapezoidal scheme across longitudes. Over a wide range of strain states, fiber
      material properties, and fiber angular distributions, results demonstrate that
      this new scheme always outperforms FEI, sometimes by orders of magnitude in the
      number of computational steps and relative accuracy of the stress calculation. 

PMID- 26291493
TI  - Potential of BODIPY-cholesterol for analysis of cholesterol transport and
      diffusion in living cells.
AB  - Cholesterol is an abundant and important lipid component of cellular membranes.
      Analysis of cholesterol transport and diffusion in living cells is hampered by
      the technical challenge of designing suitable cholesterol probes which can be
      detected for example by optical microscopy. One strategy is to use intrinsically
      fluorescent sterols, as dehydroergosterol (DHE), having minimal chemical
      alteration compared to cholesterol but giving low fluorescence signals in the UV
      region of the spectrum. Alternatively, one can use dye-tagged cholesterol analogs
      and in particular BODIPY-cholesterol (BChol), whose synthesis and initial
      characterization was pioneered by Robert Bittman. Here, we give a general
      overview of the properties and applications but also limitations of BODIPY-tagged
      cholesterol probes for analyzing intracellular cholesterol trafficking. We
      describe our own experiences and collaborative efforts with Bob Bittman for
      studying diffusion in the plasma membrane (PM) and uptake of BChol in a
      quantitative manner. For that purpose, we used a variety of fluorescence
      approaches including fluorescence correlation spectroscopy and its imaging
      variants, fluorescence recovery after photobleaching (FRAP) and fluorescence loss
      in photobleaching (FLIP). We also describe pulse-chase studies from the PM using
      BChol in direct comparison to DHE. Based on the gathered imaging data, we present
      a two-step kinetic model for sterol transport between PM and recycling endosomes.
      In addition, we highlight the suitability of BChol for determining transport of
      lipoprotein-derived sterol using electron microscopy (EM) and show that this
      approach ideally complements fluorescence studies. 

PMID- 26291494
TI  - Introduction to the special issue: Inhibitors of enzymes involved in lipid
      metabolism.

PMID- 26291495
TI  - Perspectives on the membrane fatty acid unsaturation/pacemaker hypotheses of
      metabolism and aging.
AB  - The membrane pacemaker hypotheses of metabolism and aging are distinct, but
      interrelated hypotheses positing that increases in unsaturation of lipids within
      membranes are correlated with increasing basal metabolic rate and decreasing
      longevity, respectively. The two hypotheses each have evidence that either
      supports or contradicts them, but consensus has failed to emerge. In this review,
      we identify sources of weakness of previous studies supporting and contradicting
      these hypotheses and suggest different methods and lines of inquiry. The link
      between fatty acyl composition of membranes and membrane-bound protein activity
      is a central tenet of the membrane pacemaker hypothesis of metabolism, but the
      mechanism by which unsaturation would change protein activity is not well defined
      and, whereas fatty acid desaturases have been put forward by some as the
      mechanism behind evolutionary differences in fatty acyl composition of
      phospholipids among organisms, there have been no studies to differentiate
      whether desaturases have been more affected by natural selection on aging and
      metabolic rate than have elongases or acyltransferases. Past analyses have been
      hampered by potentially incorrect estimates of the peroxidizability of lipids and
      longevity of study animals, and by the confounding effect of phylogeny. According
      to some authors, body mass may also be a confounding effect that should be taken
      into account, though this is not universally accepted. Further research on this
      subject should focus more on mechanisms and take weaknesses of past studies into
      account. 

PMID- 26291496
TI  - Reliability of measurement of endothelial function across multiple institutions
      and establishment of reference values in Japanese.
AB  - AIMS: For the standardization of flow-mediated vasodilatation (FMD) assessment as
      a clinical tool, validation of its reliability across multiple institutions and
      the establishment of normal/reference values based on reliable data from multiple
      institutions are needed. METHODS AND RESULTS: In Study 1, assessment of FMD (scan
      recording and analysis) using an ultrasonographic semi-automatic measuring system
      (sFMD) was conducted at 18 participating institutions (sFMD-INST) (n = 981). All
      of the brachial arterial scans were also analyzed at a core laboratory (sFMD
      COLB). After 111 subjects with inadequate sFMD recordings were excluded (n =
      880), the correlation between the sFMD-INST and sFMD-COLB improved from R = 0.725
      to R = 0.838 (p < 0.001). In Study 2, based on good-quality sFMD data obtained
      from 6660 subjects without cardiovascular disease (CVD) and 729 subjects with CVD
      from 27 institutions, reference values of sFMD are proposed by the Framingham
      risk score (FRS)-based risk categories and according to gender and age. The
      receiver-operating characteristic curve analysis revealed a significant power of
      sFMD values in reference ranges to discriminate between subjects with and without
      CVD (e.g., area under curve = 0.64 in the FRS-low risk group). CONCLUSIONS: When
      the analysis was limited to cases with clear sFMD recordings, the reliability of
      the sFMD assessment (scan and its analysis) conducted in individual institutions
      appeared to be acceptable. Reference sFMD values (lower cuff occlusion) for the
      Japanese population are proposed based on reliable data derived from multiple
      institutions, and the reference values may identify patients without advanced
      vascular damage.

PMID- 26291497
TI  - Cholesterol trafficking-related serum lipoprotein functions in children with
      cholesteryl ester storage disease.
AB  - OBJECTIVE: Serum lipoproteins influence cell cholesterol content by delivering
      and removing cholesterol to/from cells, functions mainly exerted by LDL and HDL,
      respectively. Especially in the case of HDL, structure and composition are
      crucial for function, beyond serum levels. Cholesteryl ester storage disease
      (CESD) is caused by LIPA gene mutations and reduced activity of lysosomal acid
      lipase (LAL), the enzyme responsible for hydrolysis of cholesteryl esters and TG.
      CESD patients typically present dyslipidaemia, liver damage and premature
      atherosclerosis. The objective of this work was to evaluate serum HDL cholesterol
      efflux capacity (CEC) and serum cholesterol loading capacity (CLC) in CESD
      pediatric patients and to study lipoprotein qualitative modifications. METHODS:
      HDL CEC was evaluated by radioisotopic techniques, serum CLC was measured by a
      fluorimetric assay, HDL subclasses were determined by two-dimensional
      electrophoresis. RESULTS: CESD patients (n = 3) displayed on average increased
      LDL cholesterol (+163%; p = 0.019), TG (+203; p = 0.012), phospholipids (+40%; p
      = 0.024) and lower HDL cholesterol (-57%; p = 0.012) compared to controls (n =
      9). CESD HDL CEC was impaired both as a whole (average reduction of 26%; p <
      0.0001) and with respect to specific membrane cholesterol transporters (-23% for
      aqueous diffusion; p = 0.005; -32% for ABCA1-efflux; p = 0.0002; -60% for SR-BI
      efflux; p < 0.0001; -42% for ABCG1-efflux p = 0.0003). A marked reduction in the
      pre-beta HDL concentration (-69%; p = 0.012) was detected. Finally, CESD serum
      CLC was significantly increased (+21%; p = 0.0007). CONCLUSION: These new data
      demonstrate that the pro-atherogenic modifications of serum include disturbances
      in lipoprotein functions involved in cell cholesterol homeostasis occurring from
      very early age in CESD patients.

PMID- 26291498
TI  - The p53 inhibitor, pifithrin-alpha, disrupts microtubule organization, arrests
      growth, and induces polyploidy in the rainbow trout gill cell line, RTgill-W1.
AB  - Pifithrin-alpha (PFT-alpha) blocks p53-dependent transcription and is an example
      of the many drugs being developed to target the p53 pathway in humans that could
      be released into the environment with potential impacts on aquatic animals if
      they were to become successful pharmaceuticals. In order to understand how p53
      drugs might act on fish, the effects of PFT-alpha on rainbow trout gill
      epithelial cell line, RTgill-W1, were studied. PFT-alpha was not cytotoxic to
      RTgill-W1 in cultures with or without fetal bovine serum (FBS), but at
      5.25MUg/ml, PFT-alpha completely arrested proliferation. When FBS was present,
      PFT-alpha increased the number of polyploid cells over 12days. Those results
      suggest that like in mammals, p53 appears to regulate ploidy in fish. However,
      several effects were seen that have not been observed with mammalian cells. PFT
      alpha caused a transient rise in the mitotic index and a disruption in
      cytoskeletal microtubules. These results suggest that in fish cells PFT-alpha
      affects microtubules either directly through an off-target action on tubulin or
      indirectly through an on-target action on p53-regulated transcription. 

PMID- 26291500
TI  - A porous Zr-cluster-based cationic metal-organic framework for highly efficient
      Cr2O7(2-) removal from water.
AB  - A cationic robust Zr-cluster-based metal-organic framework has been developed for
      the efficient removal of Cr2O7(2-) from aqueous solutions. 

PMID- 26291499
TI  - Postradiation Extraskeletal Osteosarcoma Masquerading as an Axillary Artery
      Pseudoaneurysm.
AB  - BACKGROUND: A 68-year-old woman with a thoracoabdominal aortic aneurysm recently
      status after first-stage elephant trunk procedure with right brachiocephalic
      artery endarterectomy and reimplantation of the innominate and left carotid using
      a 14 * 10-mm branch graft presented to clinic with increasing pain in her right
      arm and shoulder for 2 weeks. She also had a remote history of radiation to the
      right axilla for breast cancer. On physical examination, she had a tender mass
      under her clavicle, numbness in shoulder and right hand weakness. Computed
      tomography scan revealed a 5.3 * 4.3-cm coarsely rim calcified lesion in the
      right axillary region reported as a pseudoaneurysm. METHODS: She was taken to the
      operating room for exploration. After obtaining proximal and distal control, the
      mass revealed to be a solid tumor. The mass was removed, taking care to avoid the
      axillary artery and medial and lateral cords of the brachial plexus. RESULTS:
      Pathology revealed an extraskeletal osteosarcoma. CONCLUSIONS: Extraskeletal
      osteosarcoma is an extremely rare primary bone cancer, making up <1% of all
      osteosarcomas. Less than 350 cases are described in the literature. Of the cases
      described in the literature, less than 5% involve the upper extremity and/or
      thorax. They are aggressive tumors located in the soft tissue and not an
      extension of bone. Treatment involves multimodality therapy with surgical
      resection and adjuvant chemoradiation.

PMID- 26291501
TI  - Mechanics and morphogenesis of fission yeast cells.
AB  - The integration of biochemical and biomechanical elements is at the heart of
      morphogenesis. While animal cells are relatively soft objects which shape and
      mechanics is mostly regulated by cytoskeletal networks, walled cells including
      those of plants, fungi and bacteria are encased in a rigid cell wall which resist
      high internal turgor pressure. How these particular mechanical properties may
      influence basic cellular processes, such as growth, shape and division remains
      poorly understood. Recent work using the model fungal cell fission yeast,
      Schizosaccharomyces pombe, highlights important contribution of cell mechanics to
      various morphogenesis processes. We envision this genetically tractable system to
      serve as a novel standard for the mechanobiology of walled cell. 

PMID- 26291502
TI  - Recommendations for the inclusion of targeted testing to improve the regulatory
      environmental risk assessment of veterinary medicines used in aquaculture.

PMID- 26291503
TI  - Chemotherapy--A Viable Partner for Cancer Immunotherapy?

PMID- 26291504
TI  - Prediction of post-operative range of motion using intra-operative soft tissue
      balance in total knee arthroplasty with navigation.
AB  - This study evaluated the influence of intra-operative soft tissue balance on post
      operative range of motion in patients undergoing posterior-stabilized total knee
      arthroplasty with navigation. After implantation of all components in 31
      consecutive patients, the joint component gap was measured manually with the knee
      at 0 degrees , 90 degrees , and 120 degrees  as guided by a navigation system. We
      designated soft tissue balance as the absolute difference between varus stress
      and valgus stress (medio-lateral laxity). Changes in medio-lateral laxity were
      calculated from 120 degrees  to 90 degrees , 120 degrees  to 0 degrees , and 90
      degrees  to 0 degrees . Correlations among post-operative flexion angles and pre
      operative flexion angles, intra-operative flexion angle after implantation, soft
      tissue balance, and the changes were analyzed. The mean pre- and post-operative
      knee flexion angles were 114 +/- 20 degrees  and 127 +/- 9 degrees ,
      respectively. The mean intra-operative flexion angle was 137 +/- 6 degrees . The
      post-operative flexion angle was positively correlated with the pre-operative
      flexion angle and intra-operative flexion angle after implantation. The change in
      soft tissue balance between 120 degrees  and 90 degrees  showed a positive
      correlation with the post-operative flexion angle. In conclusion, Assessment of
      intra-operative soft tissue balance could predict post-operative flexion angle. 

PMID- 26291505
TI  - Measles Reemergence in Ceara, Northeast Brazil, 15 Years after Elimination.

PMID- 26291506
TI  - Survey of US Veterinary Students on Communicating with Limited English Proficient
      Spanish-Speaking Pet Owners.
AB  - Veterinary schools and colleges generally include communication skills training
      in their professional curriculum, but few programs address challenges resulting
      from language gaps between pet owners and practitioners. Due to shifting US
      demographics, small animal veterinary practices must accommodate an increasing
      number of limited English proficient (LEP) Spanish-speaking pet owners (SSPOs). A
      national survey was conducted to assess the interest and preparedness of US
      veterinary students to communicate with LEP SSPOs when they graduate. This online
      survey, with more than 2,000 first-, second-, and third-year US veterinary
      students, revealed that over 50% of students had worked at a practice or shelter
      that had LEP Spanish-speaking clients. Yet fewer than 20% of these students
      described themselves as prepared to give medical information to an LEP SSPO. Over
      three-fourths of respondents agreed that communication with LEP SSPOs was
      important for veterinarians in general, and two-thirds agreed that communication
      with LEP SSPOs was important for themselves personally. Ninety percent of
      students who described themselves as conversant in Spanish agreed that they would
      be able to communicate socially with SSPOs, while only 55% said they would be
      able to communicate medically with such clients. Overall, two-thirds of students
      expressed interest in taking Spanish for Veterinary Professionals elective course
      while in school, with the strongest interest expressed by those with advanced
      proficiency in spoken Spanish. Bridging language gaps has the potential to
      improve communication with LEP SSPOs in the veterinary clinical setting and to
      improve patient care, client satisfaction, and the economic health of the
      veterinary profession. 

PMID- 26291507
TI  - Autoimmune Metaplastic Atrophic Gastritis: Recognizing Precursor Lesions for
      Appropriate Patient Evaluation.
AB  - Autoimmune metaplastic atrophic gastritis (AMAG) is a significant risk factor for
      pernicious anemia and gastric neoplasia. Still, the histologic features of AMAG
      are frequently overlooked, especially in the early stages of the disease. The
      purpose of our study, therefore, was to catalogue the progression of histologic
      changes that precede the development of AMAG in affected individuals. Over a 2
      year period (2012 to 2014), the diagnosis of AMAG was rendered on material from
      113 patients seen at Johns Hopkins Hospital (~1.8% of "in house" gastric
      biopsies). Prior gastric body biopsies had been performed on 54 (48%) patients in
      the cohort, and the majority of these specimens had also shown AMAG. Eighteen of
      the previous biopsies, however, carried a diagnosis other than AMAG: 13 inactive
      chronic gastritis, 2 acute Helicobacter pylori gastritis, and 1 each of
      eosinophilic gastritis, iron pill gastritis, and proton-pump inhibitor-like
      effect. Upon review of these 18 biopsies, the most common histologic findings
      were heavy full-thickness or deep lamina propria chronic inflammation (12),
      inflammatory destruction of oxyntic glands (12), metaplasia (intestinal, pyloric,
      or pancreatic acinar) (10), prominent lamina propria eosinophils (8), and
      parietal cell pseudohypertrophy (4). At least 2 of these features were present in
      the majority (13, 72%) of the biopsies. In addition, 7 (58%) of these patients
      were also found to have another autoimmune or inflammatory disorder before the
      diagnosis of AMAG. Although subtle, histologic features of developing AMAG are
      identifiable in routine gastric body biopsies. When metaplasia, full-thickness
      chronic inflammation, and/or oxyntic destruction are seen, a note suggesting
      laboratory testing and/or close clinical follow-up in this subset of patients may
      be warranted. 

PMID- 26291508
TI  - Extensively Myxoid and Hyalinized Sinonasal Capillary Hemangiomas: A
      Clinicopathologic Study of 16 Cases of a Distinctive and Potentially Confusing
      Hemangioma Variant.
AB  - Capillary hemangiomas, the most common vascular tumors of the sinonasal region,
      are benign endothelial neoplasms, typically growing in an easily recognized
      lobular pattern. Some sinonasal capillary hemangiomas may show atypical features,
      such as high cellularity or mitotic activity, and represent more challenging
      diagnoses. Over the past several years we have seen in consultation a number of
      examples of sinonasal capillary hemangiomas displaying very striking stromal
      myxoid change and hyalinization, features that have received scant attention in
      the past. Available slides from 16 sinonasal capillary hemangiomas previously
      coded as showing such changes were retrieved from our archives. Submitting
      diagnoses included "query angiofibroma, rule out malignancy" (N=4), "vascular
      polyp, rule out malignancy" (N=3), "query malignant vascular tumor" (N=4),
      "sinonasal hemangiopericytoma" (N=1), and "benign vascular tumor" (N=1).
      Available radiographic studies often showed worrisome features. Grossly, the
      tumors ranged from 1.1 to 6.0 cm and appeared as ulcerated, vascular-appearing
      polyps. Microscopically, the tumors showed striking stromal myxoid change and/or
      hyalinization, which largely obscured the underlying lobular capillary
      arrangement. Within this myxohyaline matrix, a florid capillary proliferation was
      present, frequently with nonatypical mitotic activity. In some instances a
      branching, "hemangiopericytoma-like" vascular pattern was present in areas. The
      overall cellularity was low to moderate, and endothelial atypia or
      hyperchromatism was absent. Ulceration and thrombosis were frequently present.
      Immunostains to CD31, CD34, and SMA highlighted areas of lobular growth pattern
      inapparent on the routinely stained slides. Four tested cases were negative for
      androgen receptors and beta-catenin. Follow-up from 12 patients revealed no local
      recurrences or metastases. Awareness of that sinonasal capillary hemangioma may
      show these unusual stromal changes, and the use of ancillary immunohistochemistry
      to highlight its lobular growth pattern should allow its confident distinction
      from more aggressive endothelial tumors (eg, angiosarcoma) and from
      nonendothelial tumors, including nasopharyngeal angiofibroma, solitary fibrous
      tumor, and sinonasal hemangiopericytoma-like tumor. 

PMID- 26291509
TI  - Tactile Corpuscle-like Bodies in Gastrointestinal-type Mucosa: A Case Series.
AB  - Tactile corpuscle-like bodies (TCLB) are microscopic Schwannian structures that
      simulate the superficial mechanoreceptors of the peripheral nervous system
      (Wagner-Meissner corpuscles). They have been described nearly exclusively in
      peripheral nerve sheath tumors, namely diffuse neurofibromas, and schwannomas but
      also in cellular nevi. There are rare reports of these structures in the
      gastrointestinal tract (predominantly the lower tract), with the presumption that
      they are incidental reactive neural proliferations. We compiled 9 cases showing
      this rare phenomenon in gastrointestinal-type mucosa in nonsyndromic patients to
      further characterize its features. There were 6 men and 3 women (age range, 39 to
      79 y, mean 56 y) with lesions involving esophagus/gastro-esophageal junction
      (n=7), sigmoid colon (n=1), and gastric heterotopia of the cricopharynx (n=1).
      Endoscopic examination was abnormal in 6 of the 7 cases (including changes
      consistent with Barrett esophagus and polypoid/nodular mucosa) and normal in 1 of
      7 cases for which this information was available. The histologic features were
      similar in all cases, with unencapsulated clusters of lamellated and
      concentrically arranged spindle cells in the lamina propria. The foci of TCLB
      ranged in size from <0.1 to 1.5 mm in the greatest dimension. Abnormal
      histopathologic findings were identified in the background mucosa in 6 of 9 cases
      (including Barrett esophagus, active and inactive chronic gastritis,
      enterochromaffin-like cell hyperplasia, and gastric intestinal metaplasia). None
      of the patients showed signs of neurofibromatosis type 1, multiple endocrine
      neoplasia type 2B, Cowden syndrome, or other inherited syndrome. No morbidity
      related to TCLB was reported for the patients with available follow-up. 

PMID- 26291511
TI  - Pleuropulmonary Meningothelial Proliferations: Evidence for a Common
      Histogenesis.
AB  - Primary pleuropulmonary meningothelial proliferations include minute pulmonary
      meningothelial-like nodules (MPMN) and pleural or pulmonary meningiomas (PPM).
      These lesions share histologic, ultrastructural, and immunohistochemical features
      with meningiomas of the central nervous system (CNS). Meningiomas of the CNS
      exhibit a number of genetic abnormalities, most commonly loss of the
      neurofibromatosis (NF) 2 gene on chromosome 22. The molecular changes of
      pleuropulmonary meningothelial proliferations, however, have only rarely been
      investigated. This study explores the status of the NF2 gene in pleuropulmonary
      meningothelial proliferations compared with CNS meningioma using interphase
      fluorescence in situ hybridization. Whole tissue sections of 9 pleuropulmonary
      meningothelial lesions (6 MPMNs and 3 PPMs) and 9 CNS meningiomas were analyzed
      by fluorescence in situ hybridization using a commercially available locus
      specific probe for the NF2 region. Deletion of the NF2 gene was identified in 2
      MPMNs, 1 PPM, and 4 CNS meningiomas. Chromosomal gains of 22q were noted in 2
      cases of MPMN and 1 PPM. Our results indicate that pleuropulmonary meningothelial
      lesions share common genetic pathways with CNS meningiomas. In addition, they
      provide support for the hypothesis that MPMN and PPM are related lesions that may
      arise from the same precursor cell. As for CNS meningiomas, these mutational
      changes may provide additional targets for future personalized therapies. 

PMID- 26291510
TI  - Secretory Breast Carcinoma: A Histopathologic and Genomic Spectrum Characterized
      by a Joint Specific ETV6-NTRK3 Gene Fusion.
AB  - Secretory breast carcinoma (SBC) is a rare breast carcinoma with distinctive
      morphologic features and a recurrent specific chromosomal translocation
      t(12;15)(p13;q25), usually of low histologic grade and favorable prognosis. We
      describe the morphologic and genetic characteristics of 11 cases of SBC from 10
      patients. Histologic and immunohistochemical analyses, fluorescence in situ
      hybridization using break-apart probes specific to ETV6 on 12p13, reverse
      transcription polymerase chain reaction with in-house probes specific to the ETV6
      NTRK3 gene fusion, and DNA copy number variation by array comparative genomic
      hybridization analyses were performed on all cases. Seven cases were of low
      histologic grade, 3 were intermediate, and 1 had high-grade nuclear atypia,
      necrosis, and numerous mitoses. This patient had a fatal outcome. Five cases
      displayed low hormonal receptor expression, whereas the rest had basal-type
      immunoprofiles. All interpretable cases harbored an ETV6-NTRK3 gene fusion by
      reverse transcription polymerase chain reaction and/or an ETV6 rearrangement by
      fluorescence in situ hybridization, with duplication of the oncogenic derivative
      in 2 cases. Array comparative genomic hybridization analysis showed simplex
      genomic profiles. The 2 cases with ETV6-NTRK3 duplication included a gain of 12p
      starting from the ETV6 locus to the telomere, associated with a gain of the 15q
      from the centromere to NTRK3 in 1 case, and in the other a normal profile up to
      NTRK3 on 15q, and then a loss up to the telomere, suggesting loss of
      corresponding normal chromosome 15. These findings provide a novel insight into
      the morphologic and genetic spectrum of SBC, ranging from low-grade to high-grade
      histology, with occasional low hormonal receptor expression, simplex genomic
      profiles, and possible unfavorable course. 

PMID- 26291512
TI  - A Single-Atom-Thick TiO2 Nanomesh on an Insulating Oxide.
AB  - The electronic structures and macroscopic functionalities of two-dimensional (2D)
      materials are often controlled according to their size, atomic structures, and
      associated defects. This controllability is particularly important in ultrathin
      2D nanosheets of transition-metal oxides because these materials exhibit
      extraordinary multifunctionalities that cannot be realized in their bulk
      constituents. To expand the variety of materials with exotic properties that can
      be used in 2D transition-metal-oxide nanosheets, it is essential to investigate
      fabrication processes for 2D materials. However, it remains challenging to
      fabricate such 2D nanosheets, as they are often forbidden because of the crystal
      structure and nature of their host oxides. In this study, we demonstrate the
      synthesis of a single-atom-thick TiO2 2D nanosheet with a periodic array of
      holes, that is, a TiO2 nanomesh, by depositing a LaAlO3 thin film on a
      SrTiO3(001)-(?13*?13)-R33.7 degrees  reconstructed substrate. In-depth
      investigations of the detailed structures, local density of states, and Ti
      valency of the TiO2 nanomesh using scanning tunneling microscopy/spectroscopy,
      scanning transmission electron microscopy, and density functional theory
      calculations reveal an unexpected upward migration of the Ti atoms of the
      substrate surface onto the LaAlO3 surface. These results indicate that the
      truncated TiO5 octahedra on the surface of perovskite oxides are very stable,
      leading to semiconducting TiO2 nanomesh formation. This nanomesh material can be
      potentially used to control the physical and chemical properties of the surfaces
      of perovskite oxides. Furthermore, this study provides an avenue for building
      functional atomic-scale oxide 2D structures and reveals the thin-film growth
      processes of complex oxides. 

PMID- 26291514
TI  - Orientational ordering of Janus colloids in cholesteric liquid crystals.
AB  - In this paper we show that Janus colloids, which are spherical particles with
      hybrid anchoring conditions, have preferable orientations in cholesteric media
      depending on the cholesteric wave vector. Simulations reveal that the tilt angle
      of a particle varies greatly with variation of the particle diameter to the
      cholesteric pitch ratio, which makes it possible to stabilize the appropriate
      particle orientation and to control it by variation of the cholesteric pitch. 

PMID- 26291513
TI  - There Are Sex Differences in the Demographics and Risk Profiles of Emergency
      Department (ED) Patients With Atrial Fibrillation and Flutter, but no Apparent
      Differences in ED Management or Outcomes.
AB  - OBJECTIVES: In non-emergency department (ED) settings, women with atrial
      fibrillation and flutter (AFF) have different presentations, treatments, and
      outcomes than men: they are older, less likely to be treated with rhythm control
      strategies or appropriate anticoagulation, and more likely to have strokes. This
      has not been investigated in ED patients. METHODS: Records from consecutive ED
      patients from January 1 to December 31, 2009, with electrocardiogram-proven AFF
      at two urban hospitals were collected. Review of administrative and clinical data
      identified patient demographics, clinical characteristics, comorbidities, and ED
      treatments. The regional ED database was queried to determine 30-day and 1-year
      follow-up visits, and the provincial vital statistics database was referenced to
      obtain 30-day and 1-year mortality; all outcomes were stratified by sex. The
      primary outcome, which reflected overall appropriateness of ED care, was the
      proportion of patients who were discharged home at their index ED visits, who
      then had unscheduled 30-day ED revisits. Secondary outcomes included the
      proportion of eligible patients who underwent acute rhythm control strategies and
      the proportion of high-risk patients who had previously inadequately
      anticoagulation strategies corrected by the emergency physician. Additional
      outcomes included the ED length of stay (LOS) and 30-day and 1-year rates of
      stroke and death. RESULTS: A total of 1,112 records were reviewed: 470 women
      (42.3%) and 642 men. Women were a median 8 years (interquartile range = 3 to 13
      years) older than men, had higher rates of cardiovascular comorbidities, and were
      more likely to present with atypical symptoms such as weakness or dyspnea. On
      their index ED visits, 50.2% of women and 41.3% of men were admitted. At 30 days,
      39 of 234 (16.7%) women and 55 of 377 (14.6%) men who were discharged at their
      index ED visits had made revisits, for a risk difference of 2.1% (95% confidence
      interval = -3.9% to 8.5%). There were no apparent sex differences in the use of
      acute rhythm control or in the appropriateness of anticoagulation decisions. ED
      LOS was similar between women and men, as were 30-day and 1-year stroke or death
      rates. CONCLUSIONS: Female ED AFF patients were older, had more comorbidities,
      and were more likely to be admitted. However, the overall management and
      outcomes, including 30-day revisits, appeared to be similar to that of males,
      indicating that there appeared to be little sex-based discrepancy in ED care and
      outcomes.

PMID- 26291515
TI  - The association of PTPN22 rs2476601 with juvenile idiopathic arthritis is
      specific to females.
AB  - A preponderance of females develop autoimmune disease, including juvenile
      idiopathic arthritis (JIA), yet the reason for this bias remains elusive.
      Evidence suggests that genetic risk of disease may be influenced by sex. PTPN22
      rs2476601 is associated with JIA and numerous other autoimmune diseases, and has
      been reported to show female-specific association with type 1 diabetes. We
      performed main effect and sex-stratified association analyses to determine
      whether a sex-specific association exists in JIA. As expected, rs2476601 was
      associated with JIA in our discovery (413 cases and 690 controls) and replication
      (1008 cases and 9284 controls) samples. Discovery sample sex-stratified analyses
      demonstrated an association specifically in females (odds ratio (OR)=2.35, 95%
      confidence interval (CI)=1.52-3.63, P=0.00011) but not males (OR=0.91, 95%
      CI=0.52-1.60, P=0.75). This was similarly observed in the replication sample.
      There was evidence for genotype-by-sex interaction (Pinteraction=0.009). The
      association between rs2476601 and JIA appears restricted to females, partly
      accounting for the predominance of females with this disease. 

PMID- 26291516
TI  - Genome-wide association study identifies HLA 8.1 ancestral haplotype alleles as
      major genetic risk factors for myositis phenotypes.
AB  - Autoimmune muscle diseases (myositis) comprise a group of complex phenotypes
      influenced by genetic and environmental factors. To identify genetic risk factors
      in patients of European ancestry, we conducted a genome-wide association study
      (GWAS) of the major myositis phenotypes in a total of 1710 cases, which included
      705 adult dermatomyositis, 473 juvenile dermatomyositis, 532 polymyositis and 202
      adult dermatomyositis, juvenile dermatomyositis or polymyositis patients with
      anti-histidyl-tRNA synthetase (anti-Jo-1) autoantibodies, and compared them with
      4724 controls. Single-nucleotide polymorphisms showing strong associations
      (P<5*10(-8)) in GWAS were identified in the major histocompatibility complex
      (MHC) region for all myositis phenotypes together, as well as for the four
      clinical and autoantibody phenotypes studied separately. Imputation and
      regression analyses found that alleles comprising the human leukocyte antigen
      (HLA) 8.1 ancestral haplotype (AH8.1) defined essentially all the genetic risk in
      the phenotypes studied. Although the HLA DRB1*03:01 allele showed slightly
      stronger associations with adult and juvenile dermatomyositis, and HLA B*08:01
      with polymyositis and anti-Jo-1 autoantibody-positive myositis, multiple alleles
      of AH8.1 were required for the full risk effects. Our findings establish that
      alleles of the AH8.1 comprise the primary genetic risk factors associated with
      the major myositis phenotypes in geographically diverse Caucasian populations.

PMID- 26291517
TI  - The risk of upgrade for atypical ductal hyperplasia detected on magnetic
      resonance imaging-guided biopsy: a study of 100 cases from four academic
      institutions.
AB  - AIMS: To identify variables that can predict upgrade for magnetic resonance
      imaging (MRI)-detected atypical ductal hyperplasia (ADH). METHODS AND RESULTS: We
      reviewed 1655 MRI-guided core biopsies between 2005 and 2013, yielding 100 (6%)
      cases with ADH. The pathological features of ADH and MRI findings were recorded.
      An upgrade was considered when the subsequent surgical excision yielded invasive
      carcinoma (IC) or ductal carcinoma in situ (DCIS). The rate of ADH between
      institutions was 3.3-7.1%, with an average of 6%. A total of 15 (15%) cases had
      upgrade, 12 DCIS and three IC. When all cases were included, only increased
      number of involved cores was statistically significant (P = 0.02). When cases
      with concurrent lobular neoplasia (LN) were excluded (n = 14), increased number
      of ADH foci and increased number of involved cores were statistically significant
      (P = 0.002, P = 0.009). We analysed the data separately from a single institution
      (n = 61). Increased number of foci, increased number of total cores and involved
      cores and larger ADH size predicted upgrade with statistical significance.
      CONCLUSIONS: The incidence of ADH in MRI-guided core biopsy is rare. The rate of
      upgrade is comparable to mammographically detected ADH, warranting surgical
      excision. Similar to mammographically detected lesions, the volume of the ADH
      predicts the upgrade.

PMID- 26291518
TI  - Contribution of Sequence Motif, Chromatin State, and DNA Structure Features to
      Predictive Models of Transcription Factor Binding in Yeast.
AB  - Transcription factor (TF) binding is determined by the presence of specific
      sequence motifs (SM) and chromatin accessibility, where the latter is influenced
      by both chromatin state (CS) and DNA structure (DS) properties. Although SM, CS,
      and DS have been used to predict TF binding sites, a predictive model that
      jointly considers CS and DS has not been developed to predict either TF-specific
      binding or general binding properties of TFs. Using budding yeast as model, we
      found that machine learning classifiers trained with either CS or DS features
      alone perform better in predicting TF-specific binding compared to SM-based
      classifiers. In addition, simultaneously considering CS and DS further improves
      the accuracy of the TF binding predictions, indicating the highly complementary
      nature of these two properties. The contributions of SM, CS, and DS features to
      binding site predictions differ greatly between TFs, allowing TF-specific
      predictions and potentially reflecting different TF binding mechanisms. In
      addition, a "TF-agnostic" predictive model based on three DNA "intrinsic
      properties" (in silico predicted nucleosome occupancy, major groove geometry, and
      dinucleotide free energy) that can be calculated from genomic sequences alone has
      performance that rivals the model incorporating experiment-derived data. This
      intrinsic property model allows prediction of binding regions not only across
      TFs, but also across DNA-binding domain families with distinct structural folds.
      Furthermore, these predicted binding regions can help identify TF binding sites
      that have a significant impact on target gene expression. Because the intrinsic
      property model allows prediction of binding regions across DNA-binding domain
      families, it is TF agnostic and likely describes general binding potential of
      TFs. Thus, our findings suggest that it is feasible to establish a TF agnostic
      model for identifying functional regulatory regions in potentially any sequenced
      genome. 

PMID- 26291520
TI  - Write to Me Please: The Scholarly Importance of Letters to the Editor.

PMID- 26291519
TI  - Population-based study of the effect of gene expression profiling on adjuvant
      chemotherapy use in breast cancer patients under the age of 65 years.
AB  - BACKGROUND: Gene expression profiling (GEP) testing can help to predict the risk
      of cancer recurrence and guide decisions about adjuvant chemotherapy for breast
      cancer (BC). However, no prior US studies have evaluated the relation between GEP
      testing and the use of adjuvant chemotherapy by women treated in a general
      oncology practice. METHODS: Eligible patients were women under the age 65 of
      years who were newly diagnosed with their first stage I or II, hormone receptor
      positive BC between 2006 and 2011 (n = 9405). This retrospective study was
      conducted with a data set consisting of registry data, health claims data, and
      GEP testing results. The distribution of GEP test results was reported in terms
      of the risk of recurrence predicted, and logistic regression was used to assess
      the association of test results with chemotherapy use, with adjustments made for
      multiple patient characteristics. RESULTS: The proportions of tested women with
      low, intermediate, and high recurrence score results were 51%, 39%, and 10%,
      respectively. Among these women, 11%, 47%, and 88%, respectively, received
      adjuvant chemotherapy. There was a significant, positive linear relation of assay
      scores with chemotherapy use within the low and intermediate subgroups after
      adjustments for all other factors (adjusted odds ratios, 1.17 and 1.20,
      respectively). CONCLUSIONS: Adjuvant chemotherapy use after GEP testing is
      generally consistent with the recommended test interpretation for women with a
      high or low predicted risk of recurrence. Chemotherapy use in the intermediate
      risk group increased with Recurrence Score values, and evidence from ongoing
      randomized trials may help to clarify whether this finding reflects optimal
      interpretation of GEP test results. These results demonstrate the principle that
      genomic testing, on the basis of research establishing its utility, can be
      applied appropriately in general practice in accordance with guideline
      recommendations.

PMID- 26291521
TI  - Preserved conceptual implicit memory for pictures in patients with Alzheimer's
      disease.
AB  - The current study examined different aspects of conceptual implicit memory in
      patients with mild Alzheimer's disease (AD). Specifically, we were interested in
      whether priming of distinctive conceptual features versus general semantic
      information related to pictures and words would differ for the mild AD patients
      and healthy older adults. In this study, 14 healthy older adults and 15 patients
      with mild AD studied both pictures and words followed by an implicit test
      section, where they were asked about distinctive conceptual or general semantic
      information related to the items they had previously studied (or novel items).
      Healthy older adults and patients with mild AD showed both conceptual priming and
      the picture superiority effect, but the AD patients only showed these effects for
      the questions focused on the distinctive conceptual information. We found that
      patients with mild AD showed intact conceptual picture priming in a task that
      required generating a response (answer) from a cue (question) for cues that
      focused on distinctive conceptual information. This experiment has helped improve
      our understanding of both the picture superiority effect and conceptual implicit
      memory in patients with mild AD in that these findings support the notion that
      conceptual implicit memory might potentially help to drive familiarity-based
      recognition in the face of impaired recollection in patients with mild AD. 

PMID- 26291523
TI  - Health technology assessment (HTA): a brief introduction of history and the
      current status in the field of cardiology under the economic crisis.
AB  - In a time of economic recession health technology assessment is an established
      aid in decision making in many countries in order to identify cost-containment
      policy options. Moreover, as the volume, complexity, and cost of new medical
      technology increases, the need for evaluating benefits, risks and costs becomes
      increasingly important. In recent years there has been a proliferation of health
      technology assessment initiatives internationally, aimed in introducing
      rationality in the decision-making process, informing reimbursement, providing
      clinical guidance on the use of medical technologies across the world in an
      evidence-based decision-making environment and in pricing decisions. 

PMID- 26291522
TI  - Platelet Activation and Thrombus Formation over IgG Immune Complexes Requires
      Integrin alphaIIbbeta3 and Lyn Kinase.
AB  - IgG immune complexes contribute to the etiology and pathogenesis of numerous
      autoimmune disorders, including heparin-induced thrombocytopenia, systemic lupus
      erythematosus, rheumatoid- and collagen-induced arthritis, and chronic
      glomerulonephritis. Patients suffering from immune complex-related disorders are
      known to be susceptible to platelet-mediated thrombotic events. Though the role
      of the Fc receptor, FcgammaRIIa, in initiating platelet activation is well
      understood, the role of the major platelet adhesion receptor, integrin
      alphaIIbbeta3, in amplifying platelet activation and mediating adhesion and
      aggregation downstream of encountering IgG immune complexes is poorly understood.
      The goal of this investigation was to gain a better understanding of the relative
      roles of these two receptor systems in immune complex-mediated thrombotic
      complications. Human platelets, and mouse platelets genetically engineered to
      differentially express FcgammaRIIa and alphaIIbbeta3, were allowed to interact
      with IgG-coated surfaces under both static and flow conditions, and their ability
      to spread and form thrombi evaluated in the presence and absence of clinically
      used fibrinogen receptor antagonists. Although binding of IgG immune complexes to
      FcgammaRIIa was sufficient for platelet adhesion and initial signal transduction
      events, platelet spreading and thrombus formation over IgG-coated surfaces showed
      an absolute requirement for alphaIIbbeta3 and its ligands. Tyrosine kinases Lyn
      and Syk were found to play key roles in IgG-induced platelet activation events.
      Taken together, our data suggest a complex functional interplay between
      FcgammaRIIa, Lyn, and alphaIIbbeta3 in immune complex-induced platelet
      activation. Future studies may be warranted to determine whether patients
      suffering from immune complex disorders might benefit from treatment with anti
      alphaIIbbeta3-directed therapeutics. 

PMID- 26291524
TI  - Sleep Quality and Emotional Correlates in Taiwanese Coronary Artery Bypass Graft
      Patients 1 Week and 1 Month after Hospital Discharge: A Repeated Descriptive
      Correlational Study.
AB  - BACKGROUND: Poor sleep quality is a common health problem for coronary artery
      bypass graft patients, however few studies have evaluated sleep quality during
      the period immediately following hospital discharge. PURPOSE: The aim of this
      study was to investigate changes in sleep quality and emotional correlates in
      coronary artery bypass graft patients in Taiwan at 1 week and 1 month after
      hospital discharge. METHODS: We used a descriptive correlational design for this
      study. One week after discharge, 87 patients who had undergone coronary artery
      bypass surgery completed two structured questionnaires: the Pittsburgh Sleep
      Quality Index and the Hospital Anxiety and Depression Scale. Three weeks later (1
      month after discharge) the patients completed the surveys again. Pearson
      correlations, t-tests, ANOVA and linear multiple regression analysis were used to
      analyze the data. RESULTS: A majority of the participants had poor sleep quality
      at 1 week (82.8%) and 1 month (66.7%) post-hospitalization, based on the global
      score of the Pittsburgh Sleep Quality Index. Despite poor sleep quality at both
      time-points the sleep quality at 1 month was significantly better than at 1-week
      post hospitalization. Poorer sleep quality correlated with older age, poorer
      heart function, anxiety and depression. The majority of participants had normal
      levels of anxiety at 1 week (69.0%) and 1 month (88.5%) as measured by the
      Hospital Anxiety and Depression Scale. However, some level of depression was seen
      at 1 week (78.1%) and 1 month (59.7%). Depression was a significant predictor of
      sleep quality at 1 week; at 1 month after hospital discharge both anxiety and
      depression were significant predictors of sleep quality. CONCLUSION: Sleep
      quality, anxiety and depression all significantly improved 1 month after hospital
      discharge. However, more than half of the participants continued to have poor
      sleep quality and some level of depression. Health care personnel should be
      encouraged to assess sleep and emotional status in patients after coronary artery
      bypass surgery and offer them appropriate management strategies to improve sleep
      and reduce anxiety and depression.

PMID- 26291526
TI  - Changes in Inner and Outer Retinal Layer Thicknesses after Vitrectomy for
      Idiopathic Macular Hole: Implications for Visual Prognosis.
AB  - PURPOSE: To investigate sequential post-operative thickness changes in inner and
      outer retinal layers in eyes with an idiopathic macular hole (MH). METHODS:
      Retrospective case series. Twenty-four eyes of 23 patients who had received pars
      plana vitrectomy (PPV) for the closure of MH were included in the study. Spectral
      domain optical coherence tomography C-scan was used to automatically measure the
      mean thickness of the inner and outer retinal layers pre-operatively and up to 6
      months following surgery. The photoreceptor outer segment (PROS) length was
      measured manually and was used to assess its relationship with best-corrected
      visual acuity (BCVA). RESULTS: Compared with the pre-operative thickness, the
      inner layers significantly thinned during follow-up (P = 0.02), particularly in
      the parafoveal (P = 0.01), but not perifoveal, area. The post-operative inner
      layer thinning ranged from the ganglion cell layer to the inner plexiform layer
      (P = 0.002), whereas the nerve fiber layer was unaltered. Outer layer thickness
      was significantly greater post-operatively (P = 0.002), and especially the PROS
      lengthened not only in the fovea but also in the parafovea (P < 0.001). Six
      months after surgery, BCVA was significantly correlated exclusively with the
      elongated foveal PROS (R = 0.42, P = 0.03), but not with any of the other
      thickness parameters examined. CONCLUSIONS: Following PPV for MH, retinal inner
      layers other than the nerve fiber layer thinned, suggestive of subclinical
      thickening in the inner layers where no cyst was evident pre-operatively. In
      contrast, retinal outer layer thickness significantly increased, potentially as a
      result of PROS elongation linking tightly with favorable visual prognosis in MH
      eyes.

PMID- 26291527
TI  - MDA-9/Syntenin Control.
AB  - MDA-9/Syntenin is a small PDZ domain containing scaffolding protein with diverse
      array of functions regulating membrane trafficking, cell adhesion, neural, and
      synaptic development, ubiquitination, and exosome biogenesis. An appreciable
      number of studies also established a pivotal role of MDA-9/Syntenin in cancer
      development and progression. In this review, we will discuss the dynamic role of
      MDA-9/Syntenin in regulating normal and abnormal fate of various cellular
      processes.

PMID- 26291525
TI  - STAT2 Knockout Syrian Hamsters Support Enhanced Replication and Pathogenicity of
      Human Adenovirus, Revealing an Important Role of Type I Interferon Response in
      Viral Control.
AB  - Human adenoviruses have been studied extensively in cell culture and have been a
      model for studies in molecular, cellular, and medical biology. However, much less
      is known about adenovirus replication and pathogenesis in vivo in a permissive
      host because of the lack of an adequate animal model. Presently, the most
      frequently used permissive immunocompetent animal model for human adenovirus
      infection is the Syrian hamster. Species C human adenoviruses replicate in these
      animals and cause pathology that is similar to that seen with humans. Here, we
      report findings with a new Syrian hamster strain in which the STAT2 gene was
      functionally knocked out by site-specific gene targeting. Adenovirus-infected
      STAT2 knockout hamsters demonstrated an accentuated pathology compared to the
      wild-type control animals, and the virus load in the organs of STAT2 knockout
      animals was 100- to 1000-fold higher than that in wild-type hamsters. Notably,
      the adaptive immune response to adenovirus is not adversely affected in STAT2
      knockout hamsters, and surviving hamsters cleared the infection by 7 to 10 days
      post challenge. We show that the Type I interferon pathway is disrupted in these
      hamsters, revealing the critical role of interferon-stimulated genes in
      controlling adenovirus infection. This is the first study to report findings with
      a genetically modified Syrian hamster infected with a virus. Further, this is the
      first study to show that the Type I interferon pathway plays a role in inhibiting
      human adenovirus replication in a permissive animal model. Besides providing an
      insight into adenovirus infection in humans, our results are also interesting
      from the perspective of the animal model: STAT2 knockout Syrian hamster may also
      be an important animal model for studying other viral infections, including Ebola
      , hanta-, and dengue viruses, where Type I interferon-mediated innate immunity
      prevents wild type hamsters from being effectively infected to be used as animal
      models. 

PMID- 26291531
TI  - Male Sex is Associated with a Reduced Alveolar Epithelial Sodium Transport.
AB  - Respiratory distress syndrome (RDS) is the most frequent pulmonary complication
      in preterm infants. RDS incidence differs between genders, which has been called
      the male disadvantage. Besides maturation of the surfactant system, Na+ transport
      driven alveolar fluid clearance is crucial for the prevention of RDS. Na+
      transport is mediated by the epithelial Na+ channel (ENaC) and the Na,K-ATPase,
      therefore potential differences in their expression or activity possibly
      contribute to the gender imbalance observed in RDS. Fetal distal lung epithelial
      (FDLE) cells of rat fetuses were separated by sex and analyzed regarding
      expression and activity of the Na+ transporters. Ussing chamber experiments
      showed a higher baseline short-circuit current (ISC) and amiloride-sensitive
      DeltaISC in FDLE cells of female origin. In addition, maximal amiloride-sensitive
      DeltaISC and maximal ouabain-sensitive DeltaISC of female cells were higher when
      measured in the presence of a permeabilized basolateral or apical membrane,
      respectively. The number of FDLE cells per fetus recoverable during cell
      isolation was also significantly higher in females. In addition, lung wet-to-dry
      weight ratio was lower in fetal and newborn female pups. Female derived FDLE
      cells had higher mRNA levels of the ENaC- and Na,K-ATPase subunits. Furthermore,
      estrogen (ER) and progesterone receptor (PR) mRNA levels were higher in female
      cells, which might render female cells more responsive, while concentrations of
      placenta-derived sex steroids do not differ between both genders during fetal
      life. Inhibition of ER-beta abolished the sex differences in Na+ transport and
      female cells were more responsive to estradiol stimulation. In conclusion, a
      higher alveolar Na+ transport, possibly attributable to a higher expression of
      hormone receptors in female FDLE cells, provides an explanation for the well
      known sex-related difference in RDS occurrence and outcome. 

PMID- 26291532
TI  - The Enfacement Illusion Is Not Affected by Negative Facial Expressions.
AB  - Enfacement is an illusion wherein synchronous visual and tactile inputs update
      the mental representation of one's own face to assimilate another person's face.
      Emotional facial expressions, serving as communicative signals, may influence
      enfacement by increasing the observer's motivation to understand the mental state
      of the expresser. Fearful expressions, in particular, might increase enfacement
      because they are valuable for adaptive behavior and more strongly represented in
      somatosensory cortex than other emotions. In the present study, a face was seen
      being touched at the same time as the participant's own face. This face was
      either neutral, fearful, or angry. Anger was chosen as an emotional control
      condition for fear because it is similarly negative but induces less
      somatosensory resonance, and requires additional knowledge (i.e., contextual
      information and social contingencies) to effectively guide behavior. We
      hypothesized that seeing a fearful face (but not an angry one) would increase
      enfacement because of greater somatosensory resonance. Surprisingly, neither
      fearful nor angry expressions modulated the degree of enfacement relative to
      neutral expressions. Synchronous interpersonal visuo-tactile stimulation led to
      assimilation of the other's face, but this assimilation was not modulated by
      facial expression processing. This finding suggests that dynamic, multisensory
      processes of self-face identification operate independently of facial expression
      processing. 

PMID- 26291534
TI  - The impact of thiol peroxidases on redox regulation.
AB  - The biology of glutathione peroxidases and peroxiredoxins is reviewed with
      emphasis on their role in metabolic regulation. Apart from their obvious function
      in balancing oxidative challenge, these thiol peroxidases are not only implicated
      in orchestrating the adaptive response to oxidative stress, but also in
      regulating signaling triggered by hormones, growth factors and cytokines. The
      mechanisms presently discussed comprise dampening of redox-sensitive regulatory
      processes by elimination of hydroperoxides, suppression of lipoxygenase activity,
      committing suicide to save H2O2 for signaling, direct binding to receptors or
      regulatory proteins in a peroxidase activity-independent manner, or acting as
      sensors for hydroperoxides and as transducers of oxidant signals. The various
      mechanistic proposals are discussed in the light of kinetic data, which
      unfortunately are scarce. Taking into account pivotal criteria of a meaningful
      regulatory circuit, kinetic plausibility and specificity, the mechanistic
      concepts implying a direct sensor/transducer function of the thiol peroxidases
      appear most appealing. With rate constants for the reaction with hydroperoxide of
      10(5)-10(8) M(-1) s(-1), thiol peroxidases are qualified as kinetically preferred
      hydroperoxide sensors, and the ability of the oxidized enzymes to react with
      defined protein thiols lends specificity to the transduction process. The
      versatility of thiol peroxidases, however, allows multiple ways of interaction
      with regulatory pathways.

PMID- 26291533
TI  - Testing of UK Populations of Culex pipiens L. for Schmallenberg Virus Vector
      Competence and Their Colonization.
AB  - BACKGROUND: Schmallenberg virus (SBV), an arboviral pathogen of ruminants,
      emerged in northern Europe during 2011 and has subsequently spread across a vast
      geographic area. While Culicoides biting midges (Diptera: Ceratopogonidae) have
      been identified as a biological transmission agent of SBV, the role of mosquitoes
      (Diptera: Culicidae) as potential vectors has not been defined beyond small-scale
      field collections in affected areas. Culex pipiens L. are one of the most
      widespread mosquitoes in northern Europe; they are present on farms across the
      region and have previously been implicated as vectors of several other
      arboviruses. We assessed the ability of three colony lines of Cx. pipiens,
      originating from geographically diverse field populations, to become fully
      infected by SBV using semi-quantitative real-time RT-PCR (sqPCR). FINDINGS: Two
      colony lines of Cx. pipiens were created in the UK ('Brookwood' and 'Caldbeck')
      from field collections of larvae and pupae and characterised using genetic
      markers. A third strain of Cx. pipiens from CVI Wageningen, The Netherlands, was
      also screened during experiments. Intrathoracic inoculation of the Brookwood line
      resulted in infections after 14 days that were characterised by high levels of
      RNA throughout individuals, but which demonstrated indirect evidence of salivary
      gland barriers. Feeding of 322 individuals across the three colony lines on a
      membrane based infection system resulted in no evidence of full dissemination of
      SBV, although infections did occur in a small proportion of Cx. pipiens from each
      line. CONCLUSIONS/SIGNIFICANCE: This study established two novel lines of Cx.
      pipiens mosquitoes of UK origin in the laboratory and subsequently tested their
      competence for SBV. Schmallenberg virus replication and dissemination was
      restricted, demonstrating that Cx. pipiens is unlikely to be an epidemiologically
      important vector of the virus in northern Europe.

PMID- 26291535
TI  - Accuracy of preoperative T and N staging in colon cancer--a national population
      based study.
AB  - AIM: To select patients for neoadjuvant therapy in colon cancer, there is a need
      to improve pre-therapeutic locoregional staging. There are now data showing that
      the TN stage can be adequately assessed by preoperative CT in dedicated centres.
      In Sweden the use of preoperative CT of the abdomen for staging of the primary
      tumour is increasing. The aim of this study was to determine to what extent the
      preoperatively reported radiological TN stage correlates with the
      histopathological TN stage in an entire population. METHOD: Data were collected
      on the preoperative cTN stage according to the radiologist and postoperative pTN
      stage according to the pathologist on all patients operated on for colon cancer
      in Sweden 2007-2010. The correlation between cTN stage and pTN stage was
      calculated using kappa statistics. RESULTS: T stage was compared in 4373 patients
      with cT and pT stage. The correlation coefficient was 0.44, indicating fair
      agreement. The cN and pN correlation coefficient was 0.28, indicating a slight
      correlation. There was no difference in correlation related to age, gender,
      tumour location, body mass index or emergent vs elective surgery. A slight
      difference was seen between different geographical regions. CONCLUSION:
      Preoperative CT in an unselected population does not result in an accurate cTN
      staging as previously reported from dedicated centres. To achieve adequate
      preoperative cTN staging nationally, the education of radiologists and
      optimization of the radiological method will be necessary.

PMID- 26291536
TI  - Different Donor Cell Culture Methods Can Influence the Developmental Ability of
      Cloned Sheep Embryos.
AB  - It was proposed that arresting nuclear donor cells in G0/G1 phase facilitates the
      development of embryos that are derived from somatic cell nuclear transfer
      (SCNT). Full confluency or serum starvation is commonly used to arrest in vitro
      cultured somatic cells in G0/G1 phase. However, it is controversial as to whether
      these two methods have the same efficiency in arresting somatic cells in G0/G1
      phase. Moreover, it is unclear whether the cloned embryos have comparable
      developmental ability after somatic cells are subjected to one of these methods
      and then used as nuclear donors in SCNT. In the present study, in vitro cultured
      sheep skin fibroblasts were divided into four groups: (1) cultured to 70-80%
      confluency (control group), (2) cultured to full confluency, (3) starved in low
      serum medium for 4 d, or (4) cultured to full confluency and then further starved
      for 4 d. Flow cytometry was used to assay the percentage of fibroblasts in G0/G1
      phase, and cell counting was used to assay the viability of the fibroblasts.
      Then, real-time reverse transcription PCR was used to determine the levels of
      expression of several cell cycle-related genes. Subsequently, the four groups of
      fibroblasts were separately used as nuclear donors in SCNT, and the developmental
      ability and the quality of the cloned embryos were compared. The results showed
      that the percentage of fibroblasts in G0/G1 phase, the viability of fibroblasts,
      and the expression levels of cell cycle-related genes was different among the
      four groups of fibroblasts. Moreover, the quality of the cloned embryos was
      comparable after these four groups of fibroblasts were separately used as nuclear
      donors in SCNT. However, cloned embryos derived from fibroblasts that were
      cultured to full confluency combined with serum starvation had the highest
      developmental ability. The results of the present study indicate that there are
      synergistic effects of full confluency and serum starvation on arresting
      fibroblasts in G0/G1 phase, and the short-term treatment of nuclear donor cells
      with these two methods could improve the efficiency of SCNT. 

PMID- 26291538
TI  - Should the Goal for the Treatment of Soil Transmitted Helminth (STH) Infections
      Be Changed from Morbidity Control in Children to Community-Wide Transmission
      Elimination?

PMID- 26291537
TI  - Effects of Inhibiting Dipeptidyl Peptidase-4 (DPP4) in Cows with Subclinical
      Ketosis.
AB  - The inhibition of dipeptidyl peptidase-4 (DPP4) via specific inhibitors is known
      to result in improved glucose tolerance and insulin sensitivity and decreased
      accumulation of hepatic fat in type II diabetic human patients. The metabolic
      situation of dairy cows can easily be compared to the status of human diabetes
      and non-alcoholic fatty liver. For both, insulin sensitivity is reduced, while
      hepatic fat accumulation increases, characterized by high levels of non
      esterified fatty acids (NEFA) and ketone bodies.Therefore, in the present study,
      a DPP4 inhibitor was employed (BI 14332) for the first time in cows. In a first
      investigation BI 14332 treatment (intravenous injection at dosages of up to 3
      mg/kg body weight) was well tolerated in healthy lactating pluriparous cows (n =
      6) with a significant inhibition of DPP4 in plasma and liver. Further testing
      included primi- and pluriparous lactating cows suffering from subclinical ketosis
      (beta-hydroxybutyrate concentrations in serum > 1.2 mM; n = 12). The intension
      was to offer effects of DPP4 inhibition during comprehensive lipomobilisation and
      hepatosteatosis. The cows of subclinical ketosis were evenly allocated to either
      the treatment group (daily injections, 0.3 mg BI 14332/kg body weight, 7 days) or
      the control group. Under condition of subclinical ketosis, the impact of DPP4
      inhibition via BI 14332 was less, as in particular beta-hydroxybutyrate and the
      hepatic lipid content remained unaffected, but NEFA and triglyceride
      concentrations were decreased after treatment. Owing to lower NEFA, the revised
      quantitative insulin sensitivity check index (surrogate marker for insulin
      sensitivity) increased. Therefore, a positive influence on energy metabolism
      might be quite possible. Minor impacts on immune-modulating variables were
      limited to the lymphocyte CD4+/CD8+ ratio for which a trend to decreased values
      in treated versus control animals was noted. In sum, the DPP4 inhibition in cows
      did not affect glycaemic control like it is shown in humans, but was able to
      impact hyperlipemia, as NEFA and TG decreased. 

PMID- 26291539
TI  - Management of Lacrimal Gland Carcinoma: Lessons From the Literature in the Past
      40 Years.
AB  - PURPOSE: To review the published literature on management strategies for lacrimal
      gland carcinomas. METHODS: Review of relevant articles in PubMed published in
      English from the year of 1970 through September 2014. RESULTS: A review of
      literature suggests that treatment strategies for adenoid cystic carcinoma of
      lacrimal gland are varied, but local control does not necessarily prevent future
      delayed distant relapse. Tumor size and histologic features of lacrimal gland
      carcinoma seem to be important prognostic features. With improved imaging
      modalities providing better tumor diagnosis and staging, and availability of more
      focused radiation delivery techniques, multimodality globe sparing management of
      lacrimal gland carcinomas may be possible in selected cases. The availability of
      targeted drugs based on the molecular signature of an individual lacrimal gland
      carcinoma may offer possible targeted treatments for patients with nonresectable
      or metastatic disease. CONCLUSION: Given the rarity of lacrimal gland carcinoma,
      multi-institutional studies and consistent reporting of size and histologic type
      of tumors in the literature may be prudent. Particularly, multimodality globe
      sparing treatment strategies should be studied further.

PMID- 26291540
TI  - Particles with changeable topology in nematic colloids.
AB  - We show that nematic colloids can serve as a highly variable and controllable
      platform for studying inclusions with changeable topology and their effects on
      the surrounding ordering fields. We explore morphing of toroidal and knotted
      colloidal particles into effective spheres, distinctively changing their Euler
      characteristic and affecting the surrounding nematic field, including topological
      defect structures. With toroidal particles, the inner nematic defect eventually
      transitions from a wide loop to a point defect (a small loop). Trefoil particles
      become linked with two knotted defect loops, mutually forming a three component
      link, that upon tightening transform into a two-component particle-defect loop
      link. For more detailed topological analysis, Pontryagin-Thom surfaces are
      calculated and visualised, indicating an interesting cascade of defect rewirings
      caused by the shape morphing of the knotted particles. 

PMID- 26291541
TI  - Acute Respiratory Infections in Travelers Returning from MERS-CoV-Affected Areas.
AB  - We examined which respiratory pathogens were identified during screening for
      Middle East respiratory syndrome coronavirus in 177 symptomatic travelers
      returning to Ontario, Canada, from regions affected by the virus. Influenza A and
      B viruses (23.1%) and rhinovirus (19.8%) were the most common pathogens
      identified among these travelers. 

PMID- 26291542
TI  - One-Legged Cycle Training for Chronic Obstructive Pulmonary Disease. A Pragmatic
      Study of Implementation to Pulmonary Rehabilitation.
AB  - RATIONALE: In patients with chronic obstructive pulmonary disease (COPD),
      partitioned exercise training using one-legged cycling leads to greater
      improvements in peak oxygen uptake than conventional two-legged cycling.
      OBJECTIVES: We evaluated the feasibility of incorporating one-legged cycling as
      the principal aerobic training modality for pulmonary rehabilitation in COPD.
      METHODS: Physiotherapists underwent four teaching sessions about the principles
      and practical implementation of one-legged cycling training. Patients enrolled in
      a pulmonary rehabilitation program underwent 6-8 weeks of training in which one
      legged cycling three times per week was the principal aerobic exercise activity.
      Participants cycled for 15 minutes with each leg, in each session. An incremental
      cardiopulmonary exercise test was completed before and after pulmonary
      rehabilitation along with standard pulmonary rehabilitation outcome measures.
      Participants and physiotherapists completed a satisfaction survey at the end of
      the program. MEASUREMENTS AND MAIN RESULTS: A total of 22 out of 32 participants
      (14 male; mean [SD] age, 66 [7] years; FEV1% predicted, 32 [17]%; median
      [interquartile range] Medical Research Council dyspnea scale, 3.5 [3.0-4.3])
      completed pulmonary rehabilitation. Peak oxygen uptake increased 1.1 (0.4-1.7)
      ml.min(-1).kg(-1) (8%) from baseline (P<0.01). The mean (95% confidence interval)
      6-minute-walk test distance improved by 72 (45-98) m (P=0.001). The change in the
      Chronic Respiratory Questionnaire total score of 1.6 (1.1-2.1; P<0.001) was
      achieved by improvement in all four domains above the clinically important
      difference. All the physiotherapists considered one-legged cycling safe and would
      continue to prescribe it; 75% of participants would recommend it to other
      patients. CONCLUSIONS: One-legged cycling was successfully implemented into a
      "real-life" pulmonary rehabilitation program, demonstrating improvements in
      cardiorespiratory fitness with associated improvement in function for patients
      with moderate/severe COPD. One-legged cycling should be recommended in
      professional pulmonary rehabilitation guidelines as an option for exercise
      training and be available in other pulmonary rehabilitation programs. Clinical
      trial registered with www.clinicaltrials.gov (NCT01930526).

PMID- 26291543
TI  - Structural Relaxation of Photoexcited Quaterthiophenes Probed with Vibrational
      Specificity.
AB  - Ultrafast structural relaxation of photoexcited 2,2':5',2":5",2'''
      quaterthiophene (4T) and 3,3'''-Dihexyl-2,2':5',2":5",2'''-quaterthiophene (DH4T)
      in solution were interrogated with femtosecond stimulated Raman spectroscopy
      (FSRS). Relaxation was observed through time-dependent evolution in frequencies
      and intensity ratios of out-of-phase (Z) and in-phase (YA) intraring C?C
      stretching features. Frequency shifts occurred on time scales of 0.4 and 0.86 ps,
      respectively, dominated by a blue shift in the Z mode (6.2 and 11.5 cm(-1) shifts
      for 4T and DH4T, respectively). Intensity ratios evolved on similar time scales
      due to correlated intensity decreases and increases of Z- and YA-mode features.
      Excited-state quantum-chemical calculations with bithiophene demonstrate that
      mode frequencies are coupled to the torsional dihedral, such that the spectral
      evolution observed reflects excited-state relaxation toward a planar
      conformation. This work demonstrates the power of ultrafast Raman spectroscopy
      for probing dynamics in photoexcited conjugated materials with structural detail
      given the parametric dependence of intraring vibrational modes on interring
      torsional dihedrals. 

PMID- 26291544
TI  - Age and Cohort Patterns of Medical and Nonmedical Use of Controlled Medication
      Among Adolescents.
AB  - OBJECTIVES: We identified peak annual incidence rates for medical and nonmedical
      use of prescription opioid analgesics, stimulants, sedatives, and anxiolytics
      (controlled medication), and explored cohort effects on age of initiation.
      METHODS: Data were gathered retrospectively between 2009 and 2012 from Detroit
      area students (n = 5185). Modal age at the last assessment was 17 years. A meta
      analytic approach produced age-, year-, and cohort-specific risk estimates of
      first-time use of controlled medication. Cox regression models examined cohort
      patterns in age of initiation for medical and nonmedical use with any of 4
      classes of controlled medication (opioid analgesics, stimulants, sedatives, or
      anxiolytics). RESULTS: Peak annual incidence rates were observed at age 16 years,
      when 11.3% started medical use, and 3.4% started using another person's
      prescription for a controlled medication (ie, engaged in nonmedical use). In the
      more recent birth cohort group (1996-2000), 82% of medical users and 76% of
      nonmedical users reported initiating such use by age 12 years. In contrast, in
      the less recent birth cohort group (1991-1995), 42% of medical users and 35% of
      nonmedical users initiated such use by age 12 years. Time to initiation was 2.6
      times less in the more recent birth cohort group (medical use: adjusted hazard
      ratio [aHR] = 2.57 [95% confidence interval {CI} = 2.32-2.85]; nonmedical use:
      aHR = 2.57 [95% CI = 2.17-3.03]). CONCLUSIONS: Peak annual incidence rates were
      observed at age 16 years for medical and nonmedical use. More recent cohorts
      reported initiating both types of use at younger ages. Earlier interventions may
      be needed to prevent adolescent nonmedical use of controlled medication.

PMID- 26291545
TI  - Primary Care-Based Hepatitis C Treatment Outcomes With First-Generation Direct
      Acting Agents.
AB  - OBJECTIVES: Vulnerable, urban populations with a history of substance use
      disorders have a high prevalence of hepatitis C virus (HCV). Primary care-based
      treatment has been proposed to improve access to care. In this study, we present
      outcomes from our urban, primary care-based HCV treatment program in patients
      treated with telaprevir or boceprevir in combination with pegylated-interferon
      and ribavirin ("triple therapy"). METHODS: We collected data from 126 consecutive
      patients with genotype 1 HCV monoinfection seen in our treatment program (2011
      2013). Among the 40 who initiated treatment, we analyzed factors associated with
      achieving a sustained viral response (SVR). RESULTS: During the study period, 40
      patients initiated triple therapy (32%), 80% with recent or past substance use
      disorders. Patients initiating treatment were younger than untreated patients (P
      = 0.002), but otherwise did not differ demographically, or in the severity of
      their liver fibrosis (P > 0.05). An SVR was achieved in 18 patients (45%) and was
      less likely in patients with recent or past substance use disorders or
      psychiatric illness (both P < 0.01). CONCLUSIONS: Nearly one third of patients
      initiated triple therapy with SVR rates comparable to other HCV treatment
      settings, despite a significant burden of mental illness and substance
      dependence. Our experience demonstrates that a primary care-based practice can
      successfully deliver HCV care to a vulnerable population. Additional
      interventions may be needed to improve outcomes in patients with recent or past
      substance use disorders or psychiatric illness.

PMID- 26291546
TI  - Screening Community Pharmacy Patients for Risk of Prescription Opioid Misuse.
AB  - OBJECTIVES: This study tested screening feasibility and described the behavioral,
      mental, and physical health of patients filling prescriptions for opioid
      medications in the community pharmacy setting. METHODS: We conducted a cross
      sectional survey in rural/urban community pharmacies with adult noncancer
      patients. The survey included validated measures for opioid medication misuse
      risk, drug and alcohol use, and physical and mental health problems. Descriptive
      statistics were calculated, and bivariate and multivariable logistic regression
      evaluated relationships between opioid medication misuse risk and patient
      demographics, behavioral, mental, and physical health. RESULTS: A total of 164
      patients completed the survey (87% response rate), revealing positive screens for
      prescription opioid misuse risk (14.3%), illicit drug use (7.3%), hazardous
      alcohol use (21.4%), depression (25.8%), and posttraumatic stress disorder (PTSD;
      17.1%). Bivariate analyses revealed increased odds of a positive opioid
      medication misuse risk score with a positive screen for illicit drug use in the
      previous year (odds ratio = 3.91; 95% confidence interval [CI], 1.05-14.63) and
      PTSD (odds ratio = 6.7; 95% CI, 2.54-17.69). In adjusted multivariable analyses,
      these relationships strengthened such that a positive screen for illicit drug use
      (adjusted odds ratio = 12.96; 95% CI, 2.18-76.9) and PTSD (adjusted odds ratio =
      13.3; 95% CI, 3.48-50.66) increased odds for a positive opioid medication misuse
      risk score. CONCLUSIONS: Findings confirmed the feasibility of screening risk
      factors and positive opioid medication misuse risk among community pharmacy
      patients. Future research should validate these findings as a foundation to
      intervention development.

PMID- 26291547
TI  - Total Synthesis of (-)-Secu'amamine A Exploiting Type II Anion Relay Chemistry.
AB  - A total synthesis of (-)-secu'amamine A has been achieved exploiting Type II
      Anion Relay Chemistry (ARC) to provide the full linear carbon and nitrogen
      skeleton in a single flask with the requisite stereochemistry and functionality.
      A mechanistic rationale is also proposed to account for the stereochemical
      outcome of the key aldol reaction leading to the advanced aza tricyclic core. 

PMID- 26291548
TI  - Nonisotopic reagents for a cost-effective increase in sample throughput of
      targeted quantitative proteomics.
AB  - The new technology of ultrathroughput MS (uMS) transforms the intrinsic
      capability of analyte multiplexing in mass spectrometry (MS) to sample
      multiplexing. Core technological advantages of uMS rely on the decoupled use of
      isotopic quantitation reference and nonisotopic mass coding of samples. These
      advantages include: (1) high sample-throughput potential, (2) utilization of
      minimal amounts of expensive stable isotopes for the quantitation reference, and
      (3) unleashing of the open-source exploration of the chemical structure diversity
      of nonisotopic reagents to significantly enhance the MS detectability of
      analytes. A particular uMS method, ultrathroughput multiple reaction monitoring
      (uMRM), is reported for one-experiment quantitation of a surrogate peptide
      (SVILLGR) of prostate specific antigen (PSA) in multiple serum samples. Following
      derivatization of the pair of spiked, isotopic reference (SVILLGR*) and
      endogenous, native peptide in each sample, all samples were pooled for a step of
      simultaneous enrichment and cleanup of derivatized peptide pairs using
      immobilized antibody. The MS analysis of the pooled sample reported the quantity
      and sample origin of the surrogate peptide. Several analyses with different
      sample throughput were presented, with the highest being 15-in-1. Screening of
      nonisotopic reagents used combinatorial libraries of peptidyl compounds, and the
      reagent selection was based on the derivatization effectiveness and the
      capability of MS signal enhancement for the peptide. The precision, accuracy, and
      linearity of the uMRM MS technology were found to be comparable with standard
      isotope dilution MRM MS. 

PMID- 26291549
TI  - TickNET-A Collaborative Public Health Approach to Tickborne Disease Surveillance
      and Research.
AB  - TickNET, a public health network, was created in 2007 to foster greater
      collaboration between state health departments, academic centers, and the Centers
      for Disease Control and Prevention on surveillance and prevention of tickborne
      diseases. Research activities are conducted through the Emerging Infections
      Program and include laboratory surveys, high-quality prevention trials, and
      pathogen discovery. 

PMID- 26291550
TI  - Ion Pair-pi Interactions.
AB  - We report that anion-pi and cation-pi interactions can occur on the same aromatic
      surface. Interactions of this type are referred to as ion pair-pi interactions.
      Their existence, nature, and significance are elaborated in the context of
      spectral tuning, ion binding in solution, and activation of cell-penetrating
      peptides. The origin of spectral tuning by ion pair-pi interactions is unraveled
      with energy-minimized excited-state structures: The solvent- and pH-independent
      red shift of absorption and emission of push-pull fluorophores originates from
      antiparallel ion pair-pi attraction to their polarized excited state. In
      contrast, the complementary parallel ion pair-pi repulsion is spectroscopically
      irrelevant, in part because of charge neutralization by intriguing proton and
      electron transfers on excited push-pull surfaces. With time-resolved fluorescence
      measurements, very important differences between antiparallel and parallel ion
      pair-pi interactions are identified and quantitatively dissected from
      interference by aggregation and ion pair dissociation. Contributions from
      hydrogen bonding, proton transfer, pi-pi interactions, chromophore twisting, ion
      pairing, and self-assembly are systematically addressed and eliminated by concise
      structural modifications. Ion-exchange studies in solution, activation of cell
      penetrating peptides in vesicles, and computational analysis all imply that the
      situation in the ground state is complementary to spectral tuning in the excited
      state; i.e., parallel rather than antiparallel ion pair-pi interactions are
      preferred, despite repulsion from the push-pull dipole. The overall quite
      complete picture of ion pair-pi interactions provided by these remarkably
      coherent yet complex results is expected to attract attention throughout the
      multiple disciplines of chemistry involved. 

PMID- 26291551
TI  - Vis-Near-IR Spectroscopic and Time-Dependent DFT Study of Reduced Singly Bonded
      C60 Species.
AB  - Reduced fullerenes and fullerene derivatives exhibit intense absorptions in the
      vis-near-IR (vis-NIR) region. The absorptions are sensitive toward the addition
      pattern, number of addends, and oxidation state of the fullerene species and are
      used as an important benchmark for identifying anionic fullerene species. Similar
      absorptions are also shown for the reduced singly bonded C60 species, which are
      electronically different from reduced fullerene derivatives. However, much less
      work has been carried out on the vis-NIR spectroscopic study of the anionic
      singly bonded C60 species, likely due to the difficulty in controlled production
      of these species. Herein, we report the vis-NIR spectroscopic study of the mono-
      and dianions of the singly bonded C60 species (RC60(-), R(-)C60(-), and RC60(2
      *)), which are selectively generated by controlled-potential bulk electrolysis
      (CPE) of the singly bonded C60 dimer and C60 oxazolino heterocycles. Time
      dependent density functional theory (TD-DFT) calculations were performed to
      rationalize the experimental results. 

PMID- 26291552
TI  - Descartes and His Peculiar Sleep Pattern.
AB  - Rene Descartes (1596-1650) was a mathematician, philosopher, and scholar, whose
      work set a foundation for modern science. Among other interests, he focused on
      locating the "core and the seat of the soul" and concluded that the pineal gland
      was such a structure. Recent scientific findings validate Descartes' deep
      interest in pineal gland, appreciating its role as part of the circadian rhythm
      system. On the other hand, the biographical information suggests that Descartes
      had an aberration of the circadian rhythm (delayed sleep phase). Coincidentally,
      this meant that one of the most important things in his private life and one of
      the most significant areas of his research intersected in an overlooked way. 

PMID- 26291553
TI  - Sleep Quality and Recommended Levels of Physical Activity in Older People.
AB  - A minimum level of activity likely to improve sleep outcomes among older people
      has not previously been explored. In a representative UK sample aged 65+ (n =
      926), cross-sectional regressions controlling for appropriate confounders showed
      that walking at or above the internationally recommended threshold of >= 150 min
      per week was significantly associated with a lower likelihood of reporting
      insomnia symptoms (OR = 0.67, 95% CI = 0.45-0.91, p < .05). At a 4-year follow-up
      (n = 577), higher walking levels at baseline significantly predicted a lower
      likelihood of reporting sleep onset (OR = 0.64, 95% CI = 0.42-0.97, p < .05) or
      sleep maintenance (OR = 0.63, 95% CI = 0.41-0.95, p < .05) problems. These
      results are consistent with the conclusion that current physical activity
      guidelines can support sleep quality in older adults. 

PMID- 26291554
TI  - Immunogenicity and safety of a tetravalent dengue vaccine in healthy adults in
      India: A randomized, observer-blind, placebo-controlled phase II trial.
AB  - Dengue is a mosquito-borne viral disease that is endemic in India. We evaluated
      the immunogenicity and safety of recombinant, live-attenuated, tetravalent dengue
      vaccine (CYD-TDV) in Indian adults. In this observer-blind, randomized, placebo
      controlled, Phase II study, adults aged 18-45 years were randomized 2:1 to
      receive CYD-TDV or placebo at 0, 6 and 12 months in sub-cutaneous administration.
      Immunogenicity was assessed using a 50% plaque reduction neutralization test
      (PRNT50) at baseline and 28 days after each study injection. 189 participants
      were enrolled (CYD-TDV [n = 128]; placebo, [n = 61]). At baseline, seropositivity
      rates for dengue serotypes 1, 2, 3 and 4 ranged from 77.0% to 86.9%.
      Seropositivity rates for each serotype increased after each CYD-TDV injection
      with a more pronounced increase after the first injection. In the CYD-TDV group,
      geometric mean titres (GMTs) were 2.38 to 6.11-fold higher after the third
      injection compared with baseline but remained similar to baseline in the placebo
      group. In the CYD-TDV group, the GMTs were 1.66 to 4.95-fold higher and 9.23 to
      24.6-fold higher after the third injection compared with baseline in those who
      were dengue seropositive and dengue seronegative, respectively. Pain was the most
      commonly reported solicited injection site reaction after the first injection in
      both the CYD-TDV (6.3%) and placebo groups (4.9%), but occurred less frequently
      after subsequent injections. No serious adverse events were vaccine-related, no
      immediate unsolicited adverse events, and no virologically-confirmed cases of
      dengue, were reported during the study. The immunogenicity and safety of CYD-TDV
      was satisfactory in both dengue seropositive and seronegative Indian adults.

PMID- 26291555
TI  - TRAF6-Mediated SM22alpha K21 Ubiquitination Promotes G6PD Activation and NADPH
      Production, Contributing to GSH Homeostasis and VSMC Survival In Vitro and In
      Vivo.
AB  - RATIONALE: Vascular smooth muscle cell (VSMC) survival under stressful conditions
      is integral to promoting vascular repair, but facilitates plaque stability during
      the development of atherosclerosis. The cytoskeleton-associated smooth muscle
      (SM) 22alpha protein is involved in the regulation of VSMC phenotypes, whereas
      the pentose phosphate pathway plays an essential role in cell proliferation
      through the production of dihydronicotinamide adenine dinucleotide phosphate.
      OBJECTIVE: To identify the relationship between dihydronicotinamide adenine
      dinucleotide phosphate production and SM22alpha activity in the development and
      progression of vascular diseases. METHODS AND RESULTS: We showed that the
      expression and activity of glucose-6-phosphate dehydrogenase (G6PD) are promoted
      in platelet-derived growth factor (PDGF)-BB-induced proliferative VSMCs. PDGF-BB
      induced G6PD membrane translocation and activation in an SM22alpha K21
      ubiquitination-dependent manner. Specifically, the ubiquitinated SM22alpha
      interacted with G6PD and mediated G6PD membrane translocation. Furthermore, we
      found that tumor necrosis factor receptor-associated factor (TRAF) 6 mediated
      SM22alpha K21 ubiquitination in a K63-linked manner on PDGF-BB stimulation.
      Knockdown of TRAF6 decreased the membrane translocation and activity of G6PD, in
      parallel with reduced SM22alpha K21 ubiquitination. Elevated levels of activated
      G6PD consequent to PDGF-BB induction led to increased dihydronicotinamide adenine
      dinucleotide phosphate generation through stimulation of the pentose phosphate
      pathway, which enhanced VSMC viability and reduced apoptosis in vivo and in vitro
      via glutathione homeostasis. CONCLUSIONS: We provide evidence that TRAF6-induced
      SM22alpha ubiquitination maintains VSMC survival through increased G6PD activity
      and dihydronicotinamide adenine dinucleotide phosphate production. The TRAF6
      SM22alpha-G6PD pathway is a novel mechanism underlying the association between
      glucose metabolism and VSMC survival, which is beneficial for vascular repair
      after injury but facilitates atherosclerotic plaque stability.

PMID- 26291557
TI  - Wisdom and counselling: A note on advising people with HIV/AIDS in Ghana.
AB  - This article raises the question of whether the practice of HIV/AIDS counselling
      in Ghana can be linked to the wisdom that older people are said to have and use
      when they give advice to younger family members. Older people believe they have
      wisdom and life experience that young people should listen to; counsellors hold
      an opposite view about their work, insisting that it is they who listen to people
      with HIV/AIDS to help them make their own decisions. In actual practice, however,
      HIV/AIDS counsellors predominantly give information and advice, for at least
      three reasons. Firstly, clients urgently need a substantial amount of medical
      information about the causes and prevention of HIV in order to assess their
      situation and make decisions. Secondly, the traditional hierarchy between nurse
      and patient is difficult to reverse when the two meet during counselling.
      Thirdly, encouraging the client not to lose hope often takes the form of a pep
      talk, which leaves little room for listening by the counsellor. This paper pleads
      for peer counselling, as a format that combines a relative equality between
      counselling partners with the authoritative knowledge of the counsellor. This
      article is based on anthropological fieldwork among older people in a rural
      community and counsellors in a hospital in the Kwahu region of southern Ghana. 

PMID- 26291556
TI  - Human Engineered Heart Muscles Engraft and Survive Long Term in a Rodent
      Myocardial Infarction Model.
AB  - RATIONALE: Tissue engineering approaches may improve survival and functional
      benefits from human embryonic stem cell-derived cardiomyocyte transplantation,
      thereby potentially preventing dilative remodeling and progression to heart
      failure. OBJECTIVE: Assessment of transport stability, long-term survival,
      structural organization, functional benefits, and teratoma risk of engineered
      heart muscle (EHM) in a chronic myocardial infarction model. METHODS AND RESULTS:
      We constructed EHMs from human embryonic stem cell-derived cardiomyocytes and
      released them for transatlantic shipping following predefined quality control
      criteria. Two days of shipment did not lead to adverse effects on cell viability
      or contractile performance of EHMs (n=3, P=0.83, P=0.87). One month after
      ischemia/reperfusion injury, EHMs were implanted onto immunocompromised rat
      hearts to simulate chronic ischemia. Bioluminescence imaging showed stable
      engraftment with no significant cell loss between week 2 and 12 (n=6, P=0.67),
      preserving <=25% of the transplanted cells. Despite high engraftment rates and
      attenuated disease progression (change in ejection fraction for EHMs, -6.7+/-1.4%
      versus control, -10.9+/-1.5%; n>12; P=0.05), we observed no difference between
      EHMs containing viable and nonviable human cardiomyocytes in this chronic
      xenotransplantation model (n>12; P=0.41). Grafted cardiomyocytes showed enhanced
      sarcomere alignment and increased connexin 43 expression at 220 days after
      transplantation. No teratomas or tumors were found in any of the animals (n=14)
      used for long-term monitoring. CONCLUSIONS: EHM transplantation led to high
      engraftment rates, long-term survival, and progressive maturation of human
      cardiomyocytes. However, cell engraftment was not correlated with functional
      improvements in this chronic myocardial infarction model. Most importantly, the
      safety of this approach was demonstrated by the lack of tumor or teratoma
      formation.

PMID- 26291559
TI  - Temperament and Character Traits in Patients with Behcet's Disease with/without
      Eye Involvement.
AB  - PURPOSE: Ophthalmic involvement may lead to permanent vision loss in 25% of cases
      in patients with BD and it is a main concern in the literature. Although several
      studies have been investigated, the etiology and the cause of the disease and
      attacks are not yet known. This study aimed to investigate the correlation
      between visual impairment and personal characteristics and social circumstances
      in patients with BD. MATERIALS AND METHODS: A total of 153 patients with BD and
      age-and gender-matched 26 healthy control subjects completed the self-report
      Temperament and Character Inventory (TCI), Beck Depression Inventory (BDI), and
      State and Trait Anxiety Inventory (STAI-S and STAI-T). We classified the study
      participants into three groups with respect to severity of eye involvement and
      one control group. Each group was compared with the other two study groups and
      control group. RESULTS: According to TCI, we revealed that there was a trend in
      BD patients with eye involvement + poor prognosis having less disorderliness
      traits than BD patients with eye involvement + good prognosis (p = 0.016). The BD
      patients with eye involvement + poor prognosis had significantly lower attachment
      scores than BD patients with eye involvement + good prognosis (p = 0.005) and
      healthy controls (p = 0.005). The BD with eye involvement + poor prognosis had
      lower empathy scores than healthy controls (p = 0.002). In the way of average TCI
      parameters, only SD was statistically significant. In terms of subdimensions of
      TCI parameters, RD3, SD3, SD5, and C2 were shown to be statistically significant
      among some of the groups. CONCLUSION: BD patients with eye involvement were
      demonstrated to be more extravagant and socially disinterested. It may reflect
      that severe visual loss caused BD patients to be more systematic, depressive,
      self-contained, and exhausted. Considering psychological aspects of BD and its
      visual manifestations may contribute to helping these patients more effectively.

PMID- 26291558
TI  - Structural and functional studies of a Fusarium oxysporum cutinase with
      polyethylene terephthalate modification potential.
AB  - BACKGROUND: Cutinases are serine hydrolases that degrade cutin, a polyester of
      fatty acids that is the main component of plant cuticle. These biocatalysts have
      recently attracted increased biotechnological interest due to their potential to
      modify and degrade polyethylene terephthalate (PET), as well as other synthetic
      polymers. METHODS: A cutinase from the mesophilic fungus Fusarium oxysporum,
      named FoCut5a, was expressed either in the cytoplasm or periplasm of Escherichia
      coli BL21. Its X-ray structure was determined to 1.9A resolution using molecular
      replacement. The activity of the recombinant enzyme was tested on a variety of
      synthetic esters and polyester analogues. RESULTS: The highest production of
      recombinant FoCut5a was achieved using periplasmic expression at 16 degrees C.
      Its crystal structure is highly similar to previously determined Fusarium solani
      cutinase structure. However, a more detailed comparison of the surface properties
      and amino acid interactions revealed differences with potential impact on the
      biochemical properties of the two enzymes. FoCut5a showed maximum activity at 40
      degrees C and pH 8.0, while it was active on three p-nitrophenyl synthetic esters
      of aliphatic acids (C(2), C(4), C(12)), with the highest catalytic efficiency for
      the hydrolysis of the butyl ester. The recombinant cutinase was also found
      capable of hydrolyzing PET model substrates and synthetic polymers. CONCLUSIONS:
      The present work is the first reported expression and crystal structure
      determination of a functional cutinase from the mesophilic fungus F. oxysporum
      with potential application in surface modification of PET synthetic polymers.
      GENERAL SIGNIFICANCE: FoCut5a could be used as a biocatalyst in industrial
      applications for the environmentally-friendly treatment of synthetic polymers.

PMID- 26291560
TI  - OSA Syndrome and Posttraumatic Stress Disorder: Clinical Outcomes and Impact of
      Positive Airway Pressure Therapy.
AB  - BACKGROUND: We sought to determine the impact of OSA syndrome (OSAS) on symptoms
      and quality of life (QoL) among patients with posttraumatic stress disorder
      (PTSD). In addition, we assessed adherence and response to positive airway
      pressure (PAP) therapy in this population. METHODS: This was a case-controlled
      observational cohort study at the Sleep Disorders Center of an academic military
      medical center. Two hundred consecutive patients with PTSD underwent sleep
      evaluations. Patients with PTSD with and without OSAS were compared with 50
      consecutive age-matched patients with OSAS without PTSD and 50 age-matched normal
      control subjects. Polysomnographic data, sleep-related symptoms and QoL measures,
      and objective PAP usage were obtained. RESULTS: Among patients with PTSD, more
      than one-half (56.6%) received a diagnosis of OSAS. Patients with PTSD and OSAS
      had lower QoL and more somnolence compared with the other groups. Patients with
      PTSD demonstrated significantly lower adherence and response to PAP therapy.
      Resolution of sleepiness occurred in 82% of patients with OSAS alone, compared
      with 62.5% of PAP-adherent and 21.4% of nonadherent patients with PTSD and OSAS
      (P < .001). Similarly, posttreatment Functional Outcomes of Sleep Questionnaire
      >= 17.9 was achieved in 72% of patients with OSAS, compared with only 56.3% of
      patients with PTSD and OSA who were PAP adherent and 26.2% who were nonadherent
      (P < .03). CONCLUSIONS: In patients with PTSD, comorbid OSAS is associated with
      worsened symptoms, QoL, and adherence and response to PAP. Given the negative
      impact on outcomes, the possibility of OSAS should be considered carefully in
      patients with PTSD. Close follow-up is needed to optimize PAP adherence and
      efficacy in this at-risk population.

PMID- 26291561
TI  - Evaluation of Nutrition and Physical Activity Policies and Practices in Child
      Care Centers within Rural Communities.
AB  - BACKGROUND: Although some researchers have examined nutrition and physical
      activity policies within urban child care centers, little is known about the
      potentially unique needs of rural communities. METHODS: Child care centers
      serving preschool children located within low-income rural communities (n = 29)
      from seven states (Indiana, Kansas, Michigan, North Dakota, Ohio, South Dakota,
      and Wisconsin) were assessed to determine current nutrition and physical activity
      (PA) practices and policies. As part of a large-scale childhood obesity
      prevention project, the Community Healthy Living Index's previously validated
      Early Childhood Program Assessment Tool was used to collect data. Descriptive
      statistical analysis was conducted to identify high-priority areas. Healthy
      People 2020 and the Academy of Nutrition and Dietetics' recommendations for
      nutrition and PA policies in child care centers were used as benchmarks. RESULTS:
      Reports of not fully implementing (<80% of the time) recommended nutrition
      related policies or practices within rural early child care centers were
      identified. Centers not consistently serving a variety of fruits (48%),
      vegetables (45%), whole grains (41%), limiting saturated fat intake (31%),
      implementing healthy celebration guidelines (41%), involving children in mealtime
      (62%), and referring families to nutrition assistance programs (24%) were
      identified. More than one third of centers also had limited structured PA
      opportunities. Although eligible, only 48% of the centers participated in the
      Child and Adult Care Food Program. CONCLUSIONS: Overall, centers lacked parental
      outreach, staff training, and funding/resources to support nutrition and PA.
      These results provide insight into where child care centers within low-income,
      rural communities may need assistance to help prevent childhood obesity.

PMID- 26291562
TI  - Quality of Life Assessment With Orthotopic Ileal Neobladder Reconstruction After
      Radical Cystectomy: Results From a Prospective Italian Multicenter Observational
      Study.
AB  - OBJECTIVE: To assess health-related quality of life (HRQoL) parameters in
      patients who received radical cystectomy (RC) with ileal orthotopic neobladder
      (IONB) reconstruction and to identify clinic-pathologic predictors of HRQoL.
      PATIENTS AND METHODS: From January 2010 to December 2013, a multicenter,
      retrospective on 174 RC-IONB patients was carried out. All patients completed the
      following questionnaires: the European Organization for Research and Treatment of
      Cancer (EORTC) generic (QLQ-C30) and bladder cancer-specific instruments (QLQ
      BLM30) and the IONB-Patient Reported Outcome (IONB-PRO). Univariate and
      multivariate analyses were computed to identify clinic-pathologic predictors of
      HRQoL. RESULTS: Median age was 66 years (range, 31-83), and 91.4% of patients
      were men. Median follow-up period was 37 months (range, 3-247). The EORTC QLQ-C30
      revealed that age >65 years, absence of urinary incontinence, and absence of
      peripheral vascular disease were independent predictors of deteriorated body
      image. A follow-up > 36 months and the presence of urinary incontinence were
      independent predictors of worsened urinary symptoms, whereas the absence of
      urinary incontinence was an independent predictor of a worsened body image
      according to EORTC QLQ-BLM30 results. A follow-up >36 months and the absence of
      urinary incontinence were independent predictors of better functioning in terms
      of relational life, emotional life, and fatigue as revealed by the IONB-PRO.
      CONCLUSION: Age, presence of urinary incontinence, length of follow-up, and
      comorbidity status may influence postoperative HRQoL and should all be taken into
      account when counseling RC-IONB patients.

PMID- 26291563
TI  - Nonclinical Factors Predict Selection of Initial Observation for Renal Cell
      Carcinoma.
AB  - OBJECTIVE: To determine the rate of observation utilization over time and to
      identify factors influencing its use. MATERIALS AND METHODS: Using the National
      Cancer Data Base, we studied observation utilization in patients diagnosed with
      localized renal cell carcinoma from 2003 to 2010. Relationships between temporal,
      demographic, provider, and clinical factors and the likelihood of observation
      were evaluated using multivariate logistic regression. RESULTS: Of 109,410
      analyzed patients, 7047 (6.4%) underwent observation with stable use over time
      (range, 6.1% to 6.8%). Patient and disease factors were the strongest predictors
      of observation. Specifically, the odds of biopsy were 1.8-11 times higher for
      elderly or comorbid patients and 1.6-8.4 times higher for small (clinical T1a),
      biopsied, or bilateral tumors (P <.01 for all). Racial and socioeconomic factors
      also significantly predicted observation usage. In particular, observation rates
      were higher among poor, African American, and uninsured or socially insured
      patients, with these groups having 1.2-3.5 times higher odds of observation (P
      <.01). Patients receiving care at community, low-volume, or nearby hospitals were
      also significantly more likely to undergo observation (P <.01). CONCLUSION:
      Despite the continued rise in the incidence of incidental renal masses, initial
      observation use has remained stable. In accordance with treatment guidelines,
      observation is preferentially utilized in elderly and comorbid patients. However,
      nonclinical factors also predict observation use, suggesting that utilization may
      be influenced by racial and socioeconomic disparities in health care quality.

PMID- 26291564
TI  - Holmium Laser Enucleation of the Prostate Versus Bipolar Resection of the
      Prostate: A Prospective Randomized Study. "Pros and Cons".
AB  - OBJECTIVE: To compare the safety, efficacy, and applicability of holmium laser
      enucleation of the prostate (HoLEP) and bipolar transurethral resection of the
      prostate (TURPb) procedures, whereas the secondary objective is to find out the
      advantages and disadvantages of each. PATIENTS AND METHODS: A prospective
      randomized study included 120 patients with benign prostatic hyperplasia that
      required intervention. The patients were randomized in 2 equal groups: group A
      managed by HoLEP and group B managed by TURPb. The mean age, International
      Prostate Symptom Score, maximum urine flow, residual urine, operative time, blood
      loss, resected volume, catheterization time, hospital stay, and costs were
      compared. RESULTS: Both groups were comparable regarding the preoperative
      parameters. The mean operative time was statistically significantly longer in the
      HoLEP group. The drop in the hemoglobin level was statistically significantly in
      group B. The mean resected prostatic volume was 61.167 g in the HoLEP group and
      58.8 g in the TURPb group. The catheter was removed after 24 hours in 51 and 36
      patients in groups A and B, respectively. The International Prostate Symptom
      Score at 1 and 12 months and the maximum urine flow at 12 months postoperatively
      were found to be better in the HoLEP group than in the bipolar group, and this
      difference was found to be statistically significant. CONCLUSION: Although the
      HoLEP technique is associated with a relatively longer operative time, it has
      proved to be effective in treating large prostates with minimal morbidity, better
      hemostasis, less blood loss, and better voiding pattern than TURPb after a 12
      month follow-up.

PMID- 26291565
TI  - The Cytotoxicity of Layered Black Phosphorus.
AB  - Black phosphorus (BP), the latest addition to the family of 2D layered materials,
      has attracted much interest owing to potential optoelectronics, nanoelectronics,
      and biomedicine applications. Little is known about its toxicity, such as whether
      it could be as toxic as white phosphorus. In response to the possibility of BP
      employment into commercial products and biomedical devices, its cytotoxicity to
      human lung carcinoma epithelial cells (A549) was investigated. Following a 24 h
      exposure of the cells with different BP concentrations, cell viability
      assessments were conducted using water-soluble tetrazolium salt (WST-8) and
      methylthiazolyldiphenyltetrazolium bromide (MTT) assays. The toxicological
      effects were found to be dose-dependent, with BP reducing cell viabilities to 48%
      (WST-8) and 34% (MTT) at 50 MUg mL(-1) exposure. This toxicity was observed to be
      generally intermediate between that of graphene oxides and exfoliated transition
      metal dichalcogenides (MoS2, WS2, WSe2). The relatively low toxicity paves the
      way to utilization of black phosphorus.

PMID- 26291566
TI  - Considerations for randomizing 1 eye or 2 eyes--reply.

PMID- 26291568
TI  - A RAD-based phylogenetics for Orestias fishes from Lake Titicaca.
AB  - The fish genus Orestias is endemic to the Andes highlands, and Lake Titicaca is
      the centre of the species diversity of the genus. Previous phylogenetic studies
      based on a single locus of mitochondrial and nuclear DNA strongly support the
      monophyly of a group composed of many of species endemic to the Lake Titicaca
      basin (the Lake Titicaca radiation), but the relationships among the species in
      the radiation remain unclear. Recently, restriction site-associated DNA (RAD)
      sequencing, which can produce a vast number of short sequences from various loci
      of nuclear DNA, has emerged as a useful way to resolve complex phylogenetic
      problems. To propose a new phylogenetic hypothesis of Orestias fishes of the Lake
      Titicaca radiation, we conducted a cluster analysis based on morphological
      similarities among fish samples and a molecular phylogenetic analysis based on
      RAD sequencing. From a morphological cluster analysis, we recognised four species
      groups in the radiation, and three of the four groups were resolved as
      monophyletic groups in maximum-likelihood trees based on RAD sequencing data. The
      other morphology-based group was not resolved as a monophyletic group in
      molecular phylogenies, and some members of the group were diverged from its
      sister group close to the root of the Lake Titicaca radiation. The evolution of
      these fishes is discussed from the phylogenetic relationships. 

PMID- 26291570
TI  - [Clinical Assessment of the Glaucomatous Optic Disc. A Practical Guide].

PMID- 26291567
TI  - Vitamin E function and requirements in relation to PUFA.
AB  - Vitamin E (alpha-tocopherol) is recognised as a key essential lipophilic
      antioxidant in humans protecting lipoproteins, PUFA, cellular and intra-cellular
      membranes from damage. The aim of this review was to evaluate the relevant
      published data about vitamin E requirements in relation to dietary PUFA intake.
      Evidence in animals and humans indicates a minimal basal requirement of 4-5 mg/d
      of RRR-alpha-tocopherol when the diet is very low in PUFA. The vitamin E
      requirement will increase with an increase in PUFA consumption and with the
      degree of unsaturation of the PUFA in the diet. The vitamin E requirement related
      to dietary linoleic acid, which is globally the major dietary PUFA in humans, was
      calculated to be 0.4-0.6 mg of RRR-alpha-tocopherol/g of linoleic acid. Animal
      studies show that for fatty acids with a higher degree of unsaturation, the
      vitamin E requirement increases almost linearly with the degree of unsaturation
      of the PUFA in the relative ratios of 0.3, 2, 3, 4, 5 and 6 for mono-, di-, tri-,
      tetra-, penta- and hexaenoic fatty acids, respectively. Assuming a typical intake
      of dietary PUFA, a vitamin E requirement ranging from 12 to 20 mg of RRR-alpha
      tocopherol/d can be calculated. A number of guidelines recommend to increase PUFA
      intake as they have well-established health benefits. It will be prudent to
      assure an adequate vitamin E intake to match the increased PUFA intake,
      especially as vitamin E intake is already below recommendations in many
      populations worldwide. 

PMID- 26291571
TI  - [Macular Spectral Domain Optical Coherence Tomography: Clinical Evaluation].

PMID- 26291569
TI  - Rearrangement and evolution of mitochondrial genomes in parrots.
AB  - Mitochondrial genome rearrangements that result in control region duplication
      have been described for a variety of birds, but the mechanisms leading to their
      appearance and maintenance remain unclear, and their effect on sequence evolution
      has not been explored. A recent survey of mitochondrial genomes in the
      Psittaciformes (parrots) found that control region duplications have arisen
      independently at least six times across the order. We analyzed complete
      mitochondrial genome sequences from 20 parrot species, including representatives
      of each lineage with control region duplications, to document the gene order
      changes and to examine effects of genome rearrangements on patterns of sequence
      evolution. The gene order previously reported for Amazona parrots was found for
      four of the six independently derived genome rearrangements, and a previously
      undescribed gene order was found in Prioniturus luconensis, representing a fifth
      clade with rearranged genomes; the gene order resulting from the remaining
      rearrangement event could not be confirmed. In all rearranged genomes, two copies
      of the control region are present and are very similar at the sequence level,
      while duplicates of the other genes involved in the rearrangement show signs of
      degeneration or have been lost altogether. We compared rates of sequence
      evolution in genomes with and without control region duplications and did not
      find a consistent acceleration or deceleration associated with the duplications.
      This could be due to the fact that most of the genome rearrangement events in
      parrots are ancient, and additionally, to an effect of body size on evolutionary
      rate that we found for mitochondrial but not nuclear sequences. Base composition
      analyses found that relative to other birds, parrots have unusually strong
      compositional asymmetry (AT- and GC-skew) in their coding sequences, especially
      at fourfold degenerate sites. Furthermore, we found higher AT skew in species
      with control region duplications. One potential cause for this compositional
      asymmetry is that parrots have unusually slow mtDNA replication. If this is the
      case, then any replicative advantage provided by having a second control region
      could result in selection for maintenance of both control regions once
      duplicated. 

PMID- 26291572
TI  - [Tropical Ophthalmology].

PMID- 26291574
TI  - Green synthesis of CuO nanoparticles by aqueous extract of Anthemis nobilis
      flowers and their catalytic activity for the A3 coupling reaction.
AB  - CuO nanoparticles (NPs) were prepared by Anthemis nobilis flowers extract as a
      reducing and stabilizing agent and employed in catalyzing an aldehyde-amine
      alkyne coupling reaction. The synthesized CuO NPs was characterized by SEM, EDS,
      XRD, FT-IR and UV-visible techniques. A diverse range of propargylamines were
      obtained in a good to high yield. Furthermore, the separation and reuse of CuO
      NPs was very simple, effective and economical. 

PMID- 26291573
TI  - Highly stable multi-anchored magnetic nanoparticles for optical imaging within
      biofilms.
AB  - Magnetic nanoparticles are the next tool in medical diagnoses and treatment in
      many different biomedical applications, including magnetic hyperthermia as
      alternative treatment for cancer and bacterial infections, as well as the
      disruption of biofilms. The colloidal stability of the magnetic nanoparticles in
      a biological environment is crucial for efficient delivery. A surface that can be
      easily modifiable can also improve the delivery and imaging properties of the
      magnetic nanoparticle by adding targeting and imaging moieties, providing a
      platform for additional modification. The strategy presented in this work
      includes multiple nitroDOPA anchors for robust binding to the surface tied to the
      same polymer backbone as multiple poly(ethylene oxide) chains for steric
      stability. This approach provides biocompatibility and enhanced stability in
      fetal bovine serum (FBS) and phosphate buffer saline (PBS). As a proof of
      concept, these polymer-particles complexes were then modified with a near
      infrared dye and utilized in characterizing the integration of magnetic
      nanoparticles in biofilms. The work presented in this manuscript describes the
      synthesis and characterization of a nontoxic platform for the labeling of near IR
      dyes for bioimaging. 

PMID- 26291575
TI  - Displacement of facial soft tissues in upright versus supine positions.

PMID- 26291576
TI  - Vitamin D and immune function in chronic kidney disease.
AB  - The common causes of death in chronic kidney disease (CKD) patients are
      cardiovascular events and infectious disease. These patients are also predisposed
      to the development of vitamin D deficiency, which leads to an increased risk of
      immune dysfunction. Many extra-renal cells possess the capability to produce
      local active 1,25(OH)2D in an intracrine or paracrine fashion, even without
      kidney function. Vitamin D affects both the innate and adaptive immune systems.
      In innate immunity, vitamin D promotes production of cathelicidin and beta
      defensin 2 and enhances the capacity for autophagy via toll-like receptor
      activation as well as affects complement concentrations. In adaptive immunity,
      vitamin D suppresses the maturation of dendritic cells and weakens antigen
      presentation. Vitamin D also increases T helper (Th) 2 cytokine production and
      the efficiency of Treg lymphocytes but suppresses the secretion of Th1 and Th17
      cytokines. In addition, vitamin D can decrease autoimmune disease activity.
      Vitamin D has been shown to play an important role in maintaining normal immune
      function and crosstalk between the innate and adaptive immune systems. Vitamin D
      deficiency may also contribute to deterioration of immune function and infectious
      disorders in CKD patients. However, it needs more evidence to support the
      requirements for vitamin D supplementation. 

PMID- 26291577
TI  - The dietary monounsaturated to saturated fatty acid ratio modulates the genetic
      effects of GCKR on serum lipid levels in children.
AB  - BACKGROUND: Glucokinase regulator (GCKR) plays important roles in the regulation
      of glucokinase (GK) activity and the metabolism of glucose and lipids. We
      investigated whether the association between GCKR genetic variants with serum
      lipids in Korean adults is replicated in children, and whether these genetic
      influences might be modulated by dietary monounsaturated fatty acid relative to
      saturated fatty acid (MUFA:SFA) ratio. METHODS: We genotyped 711 children for
      GCKR variants, used 7495 adults in KARE database, and analyzed anthropometric,
      biochemical, and dietary measurements. RESULTS: The major allele carriers of
      rs780094 and rs780092 in adults had significantly higher serum total cholesterol
      and triglycerides levels compared to noncarriers. Five variants in children,
      including rs780094 and rs780092, correlated similarly with high total and low
      density lipoprotein (LDL) cholesterol. When the dietary MUFA:SFA ratio was
      dichotomized (MUFA:SFA>=1 or <1), the aggravating effects of the major allele on
      total cholesterol, LDL cholesterol, and triglycerides were only evident in the
      group in which MUFA:SFA ratio was <1. Additionally, we observed that the GCKR
      haplotype with a functional variant, rs1260326, influenced lower total and LDL
      cholesterol in children whose MUFA:SFA ratio was <1. CONCLUSION: We replicated
      the genetic association effect of GCKR on total cholesterol in children, and
      found that the interaction effects between GCKR genetic variants and the dietary
      MUFA:SFA ratio on lipid levels, were commonly observed in Korean adults and
      children.

PMID- 26291578
TI  - Identifying adverse drug event information in clinical notes with distributional
      semantic representations of context.
AB  - For the purpose of post-marketing drug safety surveillance, which has
      traditionally relied on the voluntary reporting of individual cases of adverse
      drug events (ADEs), other sources of information are now being explored,
      including electronic health records (EHRs), which give us access to enormous
      amounts of longitudinal observations of the treatment of patients and their drug
      use. Adverse drug events, which can be encoded in EHRs with certain diagnosis
      codes, are, however, heavily underreported. It is therefore important to develop
      capabilities to process, by means of computational methods, the more unstructured
      EHR data in the form of clinical notes, where clinicians may describe and reason
      around suspected ADEs. In this study, we report on the creation of an annotated
      corpus of Swedish health records for the purpose of learning to identify
      information pertaining to ADEs present in clinical notes. To this end, three key
      tasks are tackled: recognizing relevant named entities (disorders, symptoms,
      drugs), labeling attributes of the recognized entities (negation, speculation,
      temporality), and relationships between them (indication, adverse drug event).
      For each of the three tasks, leveraging models of distributional semantics -
      i.e., unsupervised methods that exploit co-occurrence information to model,
      typically in vector space, the meaning of words - and, in particular,
      combinations of such models, is shown to improve the predictive performance. The
      ability to make use of such unsupervised methods is critical when faced with
      large amounts of sparse and high-dimensional data, especially in domains where
      annotated resources are scarce. 

PMID- 26291579
TI  - A simple approach for the discrimination of surfactants based on the control of
      squaraine aggregation.
AB  - The color of squaraine solution shows a "fingerprint" change upon addition of
      different surfactants. A cross-responsive sensing array based on a small
      molecular probe was applied to discriminate surfactants with 100% confidence
      limits. Furthermore, the probe can selectively detect sodium dodecyl sulfate
      (SDS) with turn-on fluorescence response. 

PMID- 26291580
TI  - Beyond Mendelian randomization: how to interpret evidence of shared genetic
      predictors.
AB  - OBJECTIVE: Mendelian randomization is a popular technique for assessing and
      estimating the causal effects of risk factors. If genetic variants which are
      instrumental variables for a risk factor are shown to be additionally associated
      with a disease outcome, then the risk factor is a cause of the disease. However,
      in many cases, the instrumental variable assumptions are not plausible, or are in
      doubt. In this paper, we provide a theoretical classification of scenarios in
      which a causal conclusion is justified or not justified, and discuss the
      interpretation of causal effect estimates. RESULTS: A list of guidelines based on
      the 'Bradford Hill criteria' for judging the plausibility of a causal finding
      from an applied Mendelian randomization study is provided. We also give a
      framework for performing and interpreting investigations performed in the style
      of Mendelian randomization, but where the choice of genetic variants is
      statistically, rather than biologically motivated. Such analyses should not be
      assigned the same evidential weight as a Mendelian randomization investigation.
      CONCLUSION: We discuss the role of such investigations (in the style of Mendelian
      randomization), and what they add to our understanding of potential causal
      mechanisms. If the genetic variants are selected solely according to statistical
      criteria, and the biological roles of genetic variants are not investigated, this
      may be little more than what can be learned from a well-designed classical
      observational study.

PMID- 26291582
TI  - Cytotoxic activity, DNA damage, cellular uptake, apoptosis and western blot
      analysis of ruthenium(II) polypyridyl complex against human lung decarcinoma A549
      cell.
AB  - A new ruthenium(II) polypyridyl complex [Ru(dmp)2(pddppn)](ClO4)2Ru1 was
      synthesized and characterized. The cytotoxic activity in vitro of the complex was
      evaluated by MTT method. Ru1 shows high effect on the inhibition of the cell
      growth against BEL-7402, HeLa, MG-63 and A549 cells with low IC50 values of 1.6+/
      0.4, 9.0+/-0.8, 1.5+/-0.2 and 1.5+/-0.3 MUM, respectively. The cellular uptake
      indicates that Ru1 can enter into the cytoplasm and accumulate in the cell
      nuclei. Ru1 can induce apoptosis in A549 cells and enhance the levels of reactive
      oxygen species (ROS) and induce the decrease of mitochondrial membrane potential.
      In addition, Ru1 can down-regulate the levels of Bcl-2, Bcl-x, Bak, and Bim
      expression and up-regulate the expression of Bag-1 and Bad. The complex induces
      apoptosis of A549 cells through an intrinsic ROS-mediated mitochondrial
      dysfunction pathway, which was accompanied by regulating the expression of
      caspases and Bcl-2 family proteins.

PMID- 26291581
TI  - Low-level sodium arsenite induces apoptosis through inhibiting TrxR activity in
      pancreatic beta-cells.
AB  - In our previous study, we reported that sodium arsenite induced ROS-dependent
      apoptosis through lysosomal-mitochondrial pathway in pancreatic beta-cells. Since
      the thioredoxin (Trx) system is the key antioxidant factor in mammalian cells, we
      investigate whether the inhibition of Trx system contributes to sodium arsenite
      induced apoptosis in this study. After treatment with low-level (0.25-1MUM)
      sodium arsenite for 96h, the thioredoxin reductase (TrxR) activity was decreased
      significantly in pancreatic INS-1 cells. Following with the inactivation of TrxR,
      ASK1 was released from combining with Trx, which was evidenced by increased
      levels of ASK1 in sodium arsenite-treated INS-1 cells. Subsequently, activated
      ASK1 accelerated the expression of proapoptotic protein Bax and reduced the
      expression of anti-apoptic protein Bcl-2. Finally, low-level sodium arsenite
      induced apoptosis via caspase-3 in INS-1 cells. Knockdown of ASK1 alleviated
      sodium arsenite-induced apoptosis. In summary, the precise molecular mechanisms
      through which arsenic is related to diabetes have not been completely elucidated,
      inactivation of Trx system might provide insights into the underlying mechanisms
      at the environmental exposure levels. 

PMID- 26291583
TI  - Efficacy of Prostate-Specific Antigen Screening: Use of Regression Discontinuity
      in the PLCO Cancer Screening Trial.

PMID- 26291584
TI  - Numerical simulation of blood flow and plaque progression in carotid-carotid
      bypass patient specific case.
AB  - This study describes computer simulation of blood flow and plaque progression
      pattern in a patient who underwent surgical treatment for infected carotid
      prosthetic tube graft using carotid-carotid cross-over bypass. The 3D blood flow
      is governed by the Navier-Stokes equations, together with the continuity
      equation. Mass transfer within the blood lumen and through the arterial wall is
      coupled with the blood flow and is modelled by the convection-diffusion equation.
      Low-density lipoprotein (LDL) transport in lumen of the vessel is described by
      Kedem-Katchalsky equations. The inflammatory process is solved using three
      additional reaction-diffusion partial differential equations. Calculation based
      on a computer simulation showed that flow distribution in the left carotid artery
      (CA) was around 40-50% of the total flow in the right common CA. Also, the left
      CA had higher pressure gradient after surgical intervention. Plaque progression
      simulation predicted development of the atherosclerotic plaque in the position of
      the right common CA and the left internal CA. A novel way of atherosclerotic
      plaque progression modelling using computer simulation shows a potential clinical
      benefit with significant impact on the treatment strategy optimization. 

PMID- 26291585
TI  - Chikungunya Virus in Macaques, Malaysia.

PMID- 26291586
TI  - Role of macromolecules in the safety of use of body wash cosmetics.
AB  - One of the most challenging problems related to the use of surfactants in body
      wash cosmetics is their potential to cause skin irritations. Surfactants can bind
      with proteins, remove lipids from the epidermal surface, contribute to the
      disorganization of liquid crystal structures in the intercellular lipids, and
      interact with living skin cells. These processes can lead to skin irritations and
      allergic reactions, and impair the epidermal barrier function. The present study
      is an attempt to assess the effect of polymers and hydrolysed proteins present in
      the formulations of model body wash cosmetics on product properties. Special
      attention was given to the safety of use of this product type. The study examined
      three macromolecules: polyvinylpyrrolidone (PVP), hydrolysed wheat protein (HWP)
      and polyvinylpyrrolidone/hydrolysed wheat protein crosspolymer (PVP/HWP). The
      addition of the substances under study was found to improve the foaming
      properties of body wash cosmetics, increase their stability during storage, and
      contribute significantly to an improvement in the safety of product use by
      reducing the irritant potential. The strongest ability to reduce the skin
      irritation potential was determined for the formula enriched with the PVP/HWP
      crosspolymer. 

PMID- 26291587
TI  - Organic solvent-free low temperature method of preparation for self assembled
      amphiphilic poly(epsilon-caprolactone)-poly(ethylene glycol) block copolymer
      based nanocarriers for protein delivery.
AB  - Degradation and denaturation of labile biomolecules during preparation of
      micelles by organic solvent at high temperature are some of the limitations for
      fabrication of advanced polymer based protein delivery systems. In this paper,
      effectiveness of heat-chill method for preparation of micelles containing large
      labile biomolecules was investigated using insulin as a model protein molecule.
      Micelles (average size, <120 nm) were prepared using amphiphilic diblock and
      triblock copolymers of poly(ethylene glycol) (PEG) and poly(epsilon-caprolactone)
      (PCL). Micelles were prepared by heating PEG-PCL block copolymers with distilled
      water at 60  degrees C followed by sudden chilling in an ice-water bath. Effects
      of molecular architecture on morphology, stability and protein loading capacity
      of micelles were investigated. Micelles prepared using high molecular weight
      block copolymers exhibited good colloidal stability, encapsulation efficiency and
      insulin release characteristics. Insulin retained its secondary structure after
      micelles preparation as confirmed by CD spectroscopic study. Furthermore, in
      vitro cytotoxicity test suggested that the prepared micellar nanoparticles
      possessed biocompatibility. In a nut shell, heat-chill method of micellar
      nanoparticles preparation is well suited for encapsulating labile proteins and
      other allied biomolecules which degrade in presence of toxic organic solvents and
      at elevated temperatures.

PMID- 26291588
TI  - Sex Differences Among Career Development Awardees in the Attainment of
      Independent Research Funding in a Department of Medicine.
AB  - BACKGROUND: National data suggest that women are overall less likely than men to
      attain independent research funding. However, it remains unclear whether such sex
      differences are also observed in academic institutions that have integrated
      diversity in the workplace as a priority. METHODS: During 1999-2008, all National
      Institutes of Health (NIH) Career Development (K01, K08, or K23) awardees in the
      Department of Medicine at Johns Hopkins University School of Medicine were
      identified to investigate differences in the attainment of independent funding by
      sex, including NIH Research Project Grant (R01) or equivalent awards, (U01, P01,
      P50), and any R award (also R03, R21, R34) through 2012. RESULTS: A similar
      number of men (n = 49) and women (n = 43) received a K award. There were no
      significant sex differences in attaining an R01/equivalent award or any R award.
      The median time to attaining the first R01/equivalent award was similar for men
      and women (5.6 vs. 5.3 years, p = 0.93). The actuarial rate of R01/equivalent
      award attainment at 10 years was 64% overall (56% among men vs. 74% among women;
      log-rank p = 0.41). For any R award, the rate was 72% overall (70% among men vs.
      76% among women; log-rank p = 0.63). In Cox proportional hazards models,
      adjusting for race/ethnicity, age, Doctor of Medicine (MD) degree, and funding
      period, sex was not an independent predictor of R01/equivalent or any R award
      attainment. Interestingly, black race and/or Hispanic ethnicity significantly
      predicted any R award attainment (adjusted hazard ratio [HR] = 2.34, 95%
      confidence interval [CI] 1.02-5.37). CONCLUSIONS: No sex differences were found
      in the attainment of independent funding by K awardees in our study. Future
      studies to investigate the impact of specific diversity initiatives on subsequent
      success in attaining independent research funding are needed.

PMID- 26291589
TI  - Bu-Shen-Jian-Pi-Yi-Qi Therapy Prevents Alcohol-Induced Osteoporosis in Rats.
AB  - Bu-Shen-Jian-Pi-Yi-Qi therapy, which refers to reinforcing kidney, regulating qi,
      and invigorating spleen, is a traditional Chinese medicine, and we investigated
      its efficacy in treatment of alcohol-induced osteoporosis and its underlying
      mechanism. Forty adult male Sprague-Dawley rats were randomly assigned into
      alcohol-supplemented group, JIAN-GU-LING (JGL) group, calcium D3 + alfacalcidol
      group, and sham-treated group. Bone mineral density (BMD), bone mineral content
      (BMC), and bone biomechanical properties were assessed. Biochemical analyses of
      serum and urine specimens were detected. Reverse transcription-polymerase chain
      reaction was used to detect the mRNA level of vitamin D receptor (VDR). There
      were markedly lower bone metabolic markers and biomechanical properties in
      alcohol-supplemented group compared with sham-treated group (all P < 0.05). BMD,
      BMC, 25(OH)D3, and 1,25(OH)2D3 were elevated in JGL group relative to calcium D3
      + alfacalcidol group (all P < 0.05). U-Ca/Cr and U-P/Cr in JGL group were higher
      than those in the calcium D3 + alfacalcidol group (all P < 0.05). VDR mRNA level
      in the JGL group was elevated markedly in comparison with alcohol + calcium D3 +
      alfacalcidol group (P < 0.05). Based on our results, Bu-Shen-Jian-Pi-Yi-Qi
      therapy inhibits bone loss, promotes bone formation, and effectively improves
      bone metabolism in rats with experimental alcoholic osteoporosis. The disease
      reversal is evidenced by increased BMD and BMC, improved biomechanical
      properties, elevated VDR mRNA level, enhanced response sensitivity of 1,
      25(OH)2D3, and reduced S-Ca/P. 

PMID- 26291590
TI  - Differences in the Prediction of Area Under the Curve for a Protease Inhibitor
      Using Trough Versus Peak Concentration: Assessment Using Published
      Pharmacokinetic Data for Indinavir.
AB  - In the present day antiretroviral therapy, Ctrough is a key tool for efficacy
      assessment. The present work explored the feasibility of using Ctrough or Cmax in
      the area under the concentration-time curve (AUC) prediction of indinavir. A
      simple unweighted linear regression model was developed to describe the
      relationship between Cmax versus AUC (r = 0.8101, P < 0.001) and Ctrough versus
      AUC (r = 0.8127, P < 0.001) for indinavir. The regression lines were used to
      predict the AUC values from literature Cmax or Ctrough data of indinavir in HIV
      and healthy subjects. The fold difference, defined as the quotient of the
      observed and predicted AUC values, was evaluated along with statistical
      comparison, including root mean square error (RMSE) prediction for the 2 models.
      The correlation between Cmax versus AUC and Ctrough versus AUC was established.
      Majority of the predicted values for Cmax versus AUC were within 0.75- to 1.5
      fold differences. However, the Ctrough versus AUC model showed larger variability
      with approximately one-third of the predictions within 0.75- to 1.5-fold
      differences. The r value and %RMSE for observed versus predicted AUC for Ctrough
      (r = 0.5925, n = 65, P < 0.001, and RMSE: 67%) were inferior to the Cmax (r =
      0.8773, n = 86, P < 0.001, and RMSE: 46%). In conclusion, Cmax versus AUC and
      Ctrough versus AUC relationships were established for indinavir showing the
      utility of a single concentration time point for therapeutic drug monitoring
      purpose. The Cmax model for indinavir may be more relevant for AUC prediction as
      determined by the statistical criteria.

PMID- 26291591
TI  - Inferior ST-Elevation Acute Myocardial Infarction or an Inferior-Lead Brugada
      like Electrocardiogram Pattern Associated With the Use of Pregabalin and
      Quetiapine?
AB  - The Brugada electrocardiogram pattern is characterized by coved-type ST-elevation
      (>2 mm) in the right precordial leads. We report the case of a 62-year-old man,
      with bipolar disorder, admitted to the emergency department because of dyspnea
      and chest discomfort. The patient was on treatment with pregabalin and
      quetiapine. Unexpectedly, electrocardiogram at admission showed diffuse ST
      elevation, more evident in inferior leads, where a Brugada-like pattern was
      present. The patient underwent coronary angiography with a diagnosis of suspected
      acute coronary syndrome. Coronary angiography, however, showed mild coronary
      artery disease not requiring coronary angioplasty. Echocardiography did not
      reveal left ventricular dysfunction or pericardial effusion. Troponin levels
      remained normal over serial controls. Eventually, chest radiography showed lung
      opacities and consolidation suggestive for pneumonia. To the best of our
      knowledge, this is one of the first cases showing a transient Brugada-like
      electrocardiogram pattern in inferior leads, probably amplified by the
      administration of pregabalin and quetiapine. 

PMID- 26291592
TI  - The Reinfusion of Autogenous Shed Blood After Unilateral Total Knee Arthroplasty
      Using the Perioperative Autologous Transfusion System OrthoPAT.
AB  - This study aims to explore the use of postoperative autogenous shed blood
      reinfusion using Orthopedic Perioperative Autotransfusion System (OrthoPAT)
      system in treating patients undergoing unilateral total knee arthroplasty (TKA).
      Fifty patients undergoing unilateral TKA were enrolled as the experimental group
      A and were treated with reinfusion of autologous shed blood within 6 hours after
      unilateral TKA using OrthoPAT. Accordingly, 50 patients undergoing unilateral TKA
      were selected as the experimental group B and were treated with allogeneic blood
      transfusion. Different indexes were observed at different times. Patients in both
      groups had relatively stable hemodynamics, and there was no postoperative
      coagulopathy. Prothrombin time, thrombin time, and activated partial
      thromboplastin time were lower, and fibrinogen was higher in group A than that in
      group B 24 hours after surgery (all P < 0.05). White blood cell, red blood cell,
      hemoglobin, hematocrit (Hct), and platelet count levels in group A were lower
      than those in group B 12 hours after surgery (all P < 0.05). The postoperative
      complications of the 2 groups have significant difference (P < 0.05).
      Postoperative autogenous shed blood reinfusion using OrthoPAT system in the
      treatment of patients undergoing unilateral TKA may improve the coagulation
      function of patients and reduce the rejection caused by standard allogeneic blood
      transfusion.

PMID- 26291593
TI  - Acute Cholestatic Liver Injury From Hydralazine Intake.
AB  - Hydralazine is a commonly used oral antihypertensive agent. We report a rare case
      of hydralazine-induced hepatotoxicity in the form of subacute hepatic necrosis. A
      75-year-old African American woman presented with jaundice of 7-day duration. She
      was started on hydralazine 100 mg 3 times a day 10 weeks before presentation. On
      physical examination, scleral icterus was noted. Workup revealed elevated liver
      transaminases, alkaline phosphatase, and conjugated bilirubin. She had no history
      of liver disease, and liver function tests had been normal before starting
      hydralazine. Other etiologies, including viruses, common toxins, drugs,
      autoimmune, and copper-induced hepatitis, were excluded. Abdominal imaging
      studies did not show any evidence of intrahepatic or extrahepatic biliary ductal
      dilatation, and no pathologies were seen in the liver and pancreas. The patient's
      liver biopsy revealed extensive lobular hepatitis, significant necrosis, mixed
      inflammatory infiltrate, and no significant fibrosis, supporting a diagnosis of
      drug-induced liver injury. Hydralazine was immediately discontinued. She showed
      improvement of clinical and laboratory abnormalities within 5 days after
      discontinuation of hydralazine. To establish the diagnosis of hydralazine-induced
      liver injury, we used assessment tool outlined by the Council for International
      Organization of Medical Sciences (CIOMS) scale that led to "high probable"
      relationship. Although rare, clinically significant, and potentially life
      threatening liver injury can result from use of hydralazine. Both clinical and
      histological presentations in our patient suggest acute liver injury. The
      hydralazine-induced hepatitis seems to be reversible as discontinuation of the
      drug improves clinical outcomes. We highly recommend monitoring of the liver
      function during hydralazine treatment. 

PMID- 26291594
TI  - Evaluating the Effect of Intracoronary N-Acetylcysteine on Platelet Activation
      Markers After Primary Percutaneous Coronary Intervention in Patients With ST
      Elevation Myocardial Infarction.
AB  - During percutaneous coronary intervention (PCI), trauma occurs in the arterial
      endothelium, resulting in platelet activation and aggregation. As platelet
      aggregation may lead to coronary thrombosis, antiplatelet agents are essential
      adjunctive therapies in patients undergoing PCI. The aim of this study was to
      determine the effect of the intracoronary administration of high-dose N
      acetylcysteine (NAC) for the evaluation of its antiplatelet effects in human
      subjects. In this triple-blind trial, 147 patients undergoing primary PCI were
      enrolled. Finally, 100 patients were randomized to receive high-dose
      intracoronary NAC (100 mg/kg bolus, followed by 10 mg.kg-1.h-1 intracoronary
      continued intravenously for 12 hours) (n = 50) or dextrose solution (n = 50).
      Platelet activation biomarkers were measured before and 24 hours after the
      procedure. Secondary end points, comprising all-cause death, reinfarction, and
      target-vessel revascularization, were assessed at 30 days and 2 years. In
      comparison with the placebo, NAC could not reduce the level of platelet
      activation biomarkers within a 24-hour period after its prescription. Major
      adverse clinical events at 30 days and 2 years were infrequent and not
      statistically different between the 2 groups. Our results revealed that NAC,
      compared with the placebo, did not provide an additional clinical benefit as an
      effective antiplatelet agent after PCI.

PMID- 26291595
TI  - Hepatic Failure in a Patient Receiving Itraconazole for Pulmonary Histoplasmosis
      Case Report and Literature Review.
AB  - Severe cases of itraconazole-induced hepatotoxicity have been reported; however,
      these events are thought to occur very rarely. The available literature is
      comprised largely of individual case reports and small series that do not report
      the itraconazole serum concentration at the time of the severe adverse event or
      apply an objective scale to assess probability of the event being related to drug
      exposure. We report a case of severe hepatotoxicity after 6 months of
      itraconazole therapy for histoplasmosis, resulting in acute hepatic failure
      (aspartate transaminase >20* and alanine transaminase >15* upper limit normal),
      in the setting of therapeutic serum concentrations (5 mg/mL). Both the Naranjo
      probability scale and the Roussel Uclaf causality assessment method were used to
      assess the probability of a causality relationship showing a "probable" and
      "highly probable" association with itraconazole exposure, respectively. The
      available literature describing severe hepatotoxicity resulting in hepatic
      failure associated with itraconazole is also reviewed. 

PMID- 26291596
TI  - Successful Treatment of ANCA-Associated Vasculitis in the Setting of Common
      Variable Immunodeficiency Using Rituximab.
AB  - Autoimmune diseases such as idiopathic thrombocytopenic purpura and autoimmune
      hemolytic anemia have a high reported prevalence in patients with common variable
      immunodeficiency (CVID). We describe the case of a 36-year-old Hispanic man with
      CVID treated with intravenous immunoglobulin, who developed antineutrophilic
      cytoplasmic antibodies (ANCA)-associated vasculitis 15 years after
      immunodeficiency diagnosis. After failing first-line immunosuppressive therapy,
      the patient was successfully treated with rituximab. Although autoimmunity in the
      setting of CVID is well documented, this is the first report to describe a case
      of ANCA-associated vasculitis associated with CVID. Moreover, we report effective
      and safe use of rituximab in a patient with primary immunodeficiency. 

PMID- 26291597
TI  - Application of the Coflex Interlaminar Stabilization in Patients With L5/S1
      Degenerative Diseases: Minimum 4-Year Follow-up.
AB  - The Coflex is one of the representatives of posterior dynamic interspinous
      process device, but no study with the application of Coflex interlaminar
      stabilization in L5/S1 level has been performed. The aim of this study was to
      evaluate the feasibility and validity of the Coflex interlaminar stabilization in
      the treatment of degenerative lumbar diseases on L5/S1 level. A retrospective
      study was conducted for a consecutive series of 33 patients with degenerative
      lumbar spinal stenosis or lumbar disc herniation located in L5/S1 between
      November 2007 and September 2010. Subjects were all received decompressive
      laminectomy with implantation of Coflex device. Clinical effects were evaluated
      by visual analog scale and Oswestry Disability Index. Radiographs were done
      preoperatively, postoperatively, and at final follow-up. The Coflex devices were
      successfully implanted in all subjects. Fourteen cases completed the operations
      by inverting the prosthesis on account of too short S1 spinous processes. During
      the minimum 4-year follow-up period, all patients had obvious improvement in
      clinical effects (P < 0.05). Radiological evaluation revealed that dorsal
      intervertebral space height and intervertebral foramen height of target level
      increased significantly in all cases postoperatively and maintained well to final
      follow-up. In addition, the sagittal range of motion of operated level was
      restricted (P < 0.05), and the range of motion of adjacent segment did not change
      much (P > 0.05). The Coflex is an efficacious dynamic interspinous process device
      for the treatment of degenerative lumbar diseases that can apply to L5/S1.

PMID- 26291598
TI  - Genetic causal attributions for weight status and weight loss during a behavioral
      weight gain prevention intervention.
AB  - PURPOSE: Emerging evidence suggests that attributing one's weight to genetics may
      contribute to the adoption of obesogenic behaviors. We investigated whether
      weight-related genetic attributions were associated with weight change during a
      weight gain prevention intervention. METHODS: Participants (n = 185) were from a
      randomized clinical trial of a digital health weight gain prevention intervention
      for black women ages 25-44 years with body mass index 25.0-34.9 kg/m(2). Weight
      related genetic attributions (weight status attribution and weight loss
      attributions) were measured at baseline and 12 months. RESULTS: Among
      intervention participants, high genetic attribution for weight loss was
      associated with greater weight loss at 12 months (-2.7 vs. 0.5 kg) and 18 months
      (-3.0 vs. 0.9 kg). Among usual-care participants, high genetic attribution for
      weight status was associated with greater 18-month weight gain (2.9 vs. 0.3 kg).
      The intervention reduced the likelihood of high genetic attribution for weight
      loss at 12 months (P = 0.05). Change in the likelihood of genetic attribution was
      not associated with weight change over 12 months. CONCLUSION: Impact of genetic
      attributions on weight differs for those enrolled and not enrolled in an
      intervention. However, weight gain prevention intervention may reduce genetic
      attribution for weight loss.Genet Med 18 5, 476-482.

PMID- 26291599
TI  - What is the role of clinical genetics in the patient-centered medical home?: A
      commentary from the Medical Home Workgroup of the Heartland Regional Genetics and
      Newborn Screening Collaborative.

PMID- 26291600
TI  - Maternal medications in pregnancy and childhood asthma: Causation or association?

PMID- 26291601
TI  - Differential nuclear ATRX expression in sarcomas.
AB  - AIM: Nuclear alpha-thalassemia/mental retardation X-linked (ATRX) loss and
      alternative lengthening of telomeres (ALT) are linked in distinct malignancies.
      We therefore aimed to determine the nuclear ATRX expression correlated with ALT
      in a comprehensive series of sarcomas. METHODS AND RESULTS: A total of 573
      formalin-fixed paraffin-embedded sarcomas comprising 28 entities were
      investigated for nuclear ATRX expression by immunohistochemistry. Telomere
      specific fluorescence in-situ hybridization (FISH) was used to determine the ALT
      phenotype in 50 sarcomas with complete or heterogeneous ATRX loss. Complete
      nuclear ATRX loss was detected in 58 of 573 sarcomas, all high-grade, with the
      highest prevalence in undifferentiated pleomorphic sarcomas (38%) and pleomorphic
      liposarcomas (38%), followed by dedifferentiated liposarcomas (24%),
      osteosarcomas (21%), leiomyosarcomas (17%), myxofibrosarcomas (11%) and malignant
      peripheral nerve sheath tumours (4%). Interestingly, a further 20 sarcomas, all
      belonging to the aforementioned entities with complete ATRX loss, presented with
      a heterogeneous ATRX expression pattern. ALT was observed in 41 of 42 sarcomas
      with complete ATRX loss, but only in two of eight sarcomas with heterogeneous
      expression. CONCLUSION: Nuclear ATRX loss, either complete or heterogeneous, is
      encountered in a considerable number of high-grade sarcomas with non-specific
      genetic alterations. A causal relationship with ALT might be indicated at least
      in cases with a complete nuclear ATRX loss.

PMID- 26291602
TI  - Eosinophils: important players in humoral immunity.
AB  - Eosinophils perform numerous tasks. They are involved in inflammatory reactions
      associated with innate immune defence against parasitic infections and are also
      involved in pathological processes in response to allergens. Recently, however,
      it has become clear that eosinophils also play crucial non-inflammatory roles in
      the generation and maintenance of adaptive immune responses. Eosinophils, being a
      major source of the plasma cell survival factor APRIL (activation and
      proliferation-induced ligand), are essential not only for the long-term survival
      of plasma cells in the bone marrow, but also for the maintenance of these cells
      in the lamina propria which underlies the gut epithelium. At steady state under
      non-inflammatory conditions eosinophils are resident cells of the
      gastrointestinal tract, although only few are present in the major organized
      lymphoid tissue of the gut - the Peyer's patches (PP). Surprisingly, however,
      lack of eosinophils abolishes efficient class-switching of B cells to
      immunoglobulin (Ig)A in the germinal centres of PP. Thus, eosinophils are
      required to generate and to maintain mucosal IgA plasma cells, and as a
      consequence their absence leads to a marked reduction of IgA both in serum and in
      the gut-associated lymphoid tissues (GALT). Eosinophils thus have an essential
      part in long-term humoral immune protection, as they are crucial for the
      longevity of antibody-producing plasma cells in the bone marrow and, in addition,
      for gut immune homeostasis. 

PMID- 26291603
TI  - Scanning electron microscopy of the nail plate in onychomycosis patients with
      negative fungal culture.
AB  - Onychomycosis is a common dermatological problem and can be identified by direct
      microscopic examination and fungal culture. However, the positive rate of fungal
      culture is low. This study investigated the application of scanning electron
      microscopy in the diagnosis of onychomycosis in 20 patients with negative fungal
      culture. In this study, a routine glutaraldehyde fixation method was used to
      prepare specimens for electron microscope examination. Results showed that under
      the scanning electron microscope, significant structural damage was observed in
      the nail plate in all patients. Hyphaes were seen in 70% of cases. A mixture of
      scattered hyphaes, pseudohyphaes, and spores was observed in 30% of cases. A
      mixture of spores and bacteria was observed in 10% of cases. A mixture of hyphaes
      and bacteria was observed in 20% of cases. The typical hyphae pierced a thin
      layer or single layer of corneocytes. Hyphaes could be smooth, sleek, and
      straight with visible separation, or dry, bent, and folded with a smooth surface.
      The diameter of hyphaes was 1-2 um. The scattered spores were the main form of
      spore growth, and the growth of budding spores can be seen attached to the
      surface of layered armor. Most of the bacteria were gathered in clumps on the
      ventral surface, especially in grooves. In conclusion, scanning electron
      microscopy can be used to preliminarily identify the pathogen involved and the
      degree of damage in cases where onychomycosis is clinically diagnosed, but fungal
      culture is negative.

PMID- 26291605
TI  - Knots in soft condensed matter.

PMID- 26291604
TI  - Distinguishing between anti-platelet factor 4/heparin antibodies that can and
      cannot cause heparin-induced thrombocytopenia.
AB  - BACKGROUND: Many patients exposed to heparin develop antibodies against platelet
      factor 4 (PF4) and heparin, yet only those antibodies that activate platelets
      cause heparin-induced thrombocytopenia (HIT). Patients who produce anti
      PF4/heparin antibodies without developing HIT either have antibodies that do not
      cause platelet activation or produce pathogenic antibodies at levels that are
      insufficient to cause HIT. Understanding the differences between anti-PF4/heparin
      antibodies with and without HIT will improve test methods and reduce
      overdiagnosis. AIMS: To investigate the presence of low levels of platelet
      activating antibodies in patients investigated for HIT who had anti-PF4/heparin
      antibodies but failed to cause platelet activation in the (14) C-serotonin
      release assay (SRA). MATERIALS/METHODS: We developed a platelet activation assay
      similar to the SRA using exogenous PF4 without added heparin (PF4-SRA). This
      assay was able to detect low levels of platelet-activating antibodies. We used
      this PF4-SRA to test for platelet-activating antibodies in patients investigated
      for HIT. RESULTS: The PF4-SRA detected platelet-activating antibodies in seven
      (100%) of seven SRA-positive sera even after the samples were diluted until they
      were no longer positive in the standard SRA. Platelet-activating antibodies were
      detected in 14 (36%) of 39 patients who had anti-PF4/heparin antibodies but
      tested negative in the SRA and did not have clinical HIT. The clinical diagnosis
      of HIT was confirmed by chart review and concordant with the SRA results.
      CONCLUSIONS: A subset of heparin-treated patients produce subthreshold levels of
      platelet-activating anti-PF4/heparin antibodies that do not cause HIT. An
      increase in the titer of these pathogenic antibodies, along with permissive
      clinical conditions, could lead to HIT.

PMID- 26291606
TI  - Adequacy of PetrifilmTM Aerobic Count plates supplemented with de Man, Rogosa &
      Sharpe broth and chlorophenol red for enumeration of lactic acid bacteria in
      salami.
AB  - The present study aimed to assess the performance of alternative protocols to
      enumerate lactic acid bacteria (LAB) in salami. Fourteen cultures and two mixed
      starter cultures were plated using six protocols: 1) PetrifilmTM Aerobic Count
      (AC) with MRS broth and chlorophenol red (CR), incubated under aerobiosis or 2)
      under anaerobiosis, 3) MRS agar with CR, 4) MRS agar with bromocresol purple, 5)
      MRS agar at pH5.7, and 6) All Purpose Tween agar. Samples of salami were obtained
      and the LAB microbiota was enumerated by plating according protocols 1, 2, 3 and
      5. Regression analysis showed a significant correlation between the tested
      protocols, based on culture counts (p<0.05). Similar results were observed for
      salami, and no significant differences of mean LAB counts between selected
      protocols (ANOVA, p>0.05). Colonies were confirmed as LAB, indicating proper
      selectivity of the protocols. The results showed the adequacy of PetrifilmTM AC
      supplemented with CR for the enumeration of LAB in salami. 

PMID- 26291607
TI  - The effect of prolonged lateral positioning during routine care on regional lung
      volume changes in preterm infants.
AB  - INTRODUCTION: During routine nursing care, preterm infants are often placed in
      lateral position for several hours, but the effect of this procedure on regional
      lung volume and ventilation is unknown. In our study we examined this effect
      during 3 hrs of lateral positioning in stable preterm infants. METHODS: Preterm
      infants on non-invasive respiratory support were eligible for the study. Infants
      were placed in supine position and subsequently transferred to right or left
      lateral position, according to their individual routine nursing schedule. Changes
      in end-expiratory lung volume (EELV), tidal volume (VT ) and ventilation
      distribution were recorded using electrical impedance tomography (EIT), starting
      10 min before and up to 180 min after the positional change. Additionally, oxygen
      requirement, transcutaneous oxygen saturation and respiratory rate were recorded.
      RESULTS: 15 infants were included (GA 28.9 +/- 2.0 wk, BW 1167 +/- 290 g). EELV
      increased significantly after changing to lateral position, stabilizing at a
      median value of 40.8 (IQR 29.0-99.3) AU/kg at 30 min. This increase could almost
      be exclusively attributed to the non-dependent lung regions. Tidal volume,
      oxygenation, and respiratory rate remained stable. Changing to the right, but not
      the left, lateral position resulted in a rapid but transient shift in ventilation
      to the dependent lung regions. After 180 min there were no differences in
      ventilation distribution between lateral and supine positioning. CONCLUSION: This
      study shows that lateral position up to 3 hours, as part of normal nursing care
      of preterm infants, has no adverse effects on lung volumes and its regional
      distribution.

PMID- 26291608
TI  - A Three-Threshold Learning Rule Approaches the Maximal Capacity of Recurrent
      Neural Networks.
AB  - Understanding the theoretical foundations of how memories are encoded and
      retrieved in neural populations is a central challenge in neuroscience. A popular
      theoretical scenario for modeling memory function is the attractor neural network
      scenario, whose prototype is the Hopfield model. The model simplicity and the
      locality of the synaptic update rules come at the cost of a poor storage
      capacity, compared with the capacity achieved with perceptron learning
      algorithms. Here, by transforming the perceptron learning rule, we present an
      online learning rule for a recurrent neural network that achieves near-maximal
      storage capacity without an explicit supervisory error signal, relying only upon
      locally accessible information. The fully-connected network consists of
      excitatory binary neurons with plastic recurrent connections and non-plastic
      inhibitory feedback stabilizing the network dynamics; the memory patterns to be
      memorized are presented online as strong afferent currents, producing a bimodal
      distribution for the neuron synaptic inputs. Synapses corresponding to active
      inputs are modified as a function of the value of the local fields with respect
      to three thresholds. Above the highest threshold, and below the lowest threshold,
      no plasticity occurs. In between these two thresholds, potentiation/depression
      occurs when the local field is above/below an intermediate threshold. We
      simulated and analyzed a network of binary neurons implementing this rule and
      measured its storage capacity for different sizes of the basins of attraction.
      The storage capacity obtained through numerical simulations is shown to be close
      to the value predicted by analytical calculations. We also measured the
      dependence of capacity on the strength of external inputs. Finally, we quantified
      the statistics of the resulting synaptic connectivity matrix, and found that both
      the fraction of zero weight synapses and the degree of symmetry of the weight
      matrix increase with the number of stored patterns. 

PMID- 26291609
TI  - Successful treatment of sequential therapy in digital Bowen's disease with methyl
      aminolevulinate photodynamic therapy and topical diclofenac 3% in hyaluronan 2.5%
      gel.

PMID- 26291610
TI  - Air Pollution in China: Mapping of Concentrations and Sources.
AB  - China has recently made available hourly air pollution data from over 1500 sites,
      including airborne particulate matter (PM), SO2, NO2, and O3. We apply Kriging
      interpolation to four months of data to derive pollution maps for eastern China.
      Consistent with prior findings, the greatest pollution occurs in the east, but
      significant levels are widespread across northern and central China and are not
      limited to major cities or geologic basins. Sources of pollution are widespread,
      but are particularly intense in a northeast corridor that extends from near
      Shanghai to north of Beijing. During our analysis period, 92% of the population
      of China experienced >120 hours of unhealthy air (US EPA standard), and 38%
      experienced average concentrations that were unhealthy. China's population
      weighted average exposure to PM2.5 was 52 MUg/m3. The observed air pollution is
      calculated to contribute to 1.6 million deaths/year in China [0.7-2.2 million
      deaths/year at 95% confidence], roughly 17% of all deaths in China. 

PMID- 26291611
TI  - Melatonin protects porcine oocyte in vitro maturation from heat stress.
AB  - Melatonin is a pleiotropic molecule which plays an important role in animal
      reproductive activities. Because of the increased global warming, the impact of
      heat stress (HS) on stockbreeding has become an inevitable issue to be solved. To
      investigate the potential effects of melatonin on the in vitro maturation of
      porcine oocyte under the HS, a HS model for porcine oocyte maturation has been
      used in this study and the different concentrations of melatonin (10(-6) -10(-9) 
      m) were also tested for their protective effects on oocytes. The polar body rate,
      the index of the nuclear maturation of the oocytes, and the cleavage rate as well
      as the blastocyst rate were measured to evaluate the developmental competence of
      the oocytes after parthenogenetic activation (PA). The results showed that HS [in
      vitro maturation (IVM) 20-24 hr, 42 degrees C] significantly reduced the polar
      body rate of oocytes and the blastocyte rate of porcine PA embryos, while
      melatonin (10(-7)  m) application not only improved polar body rate and
      blastocyte rate, but also preserved the normal levels of steroid hormone which is
      disrupted by HS. The presence of melatonin (10(-7)  m) during the oocyte
      maturation under the HS reduced reactive oxygen species (ROS) formation, enhanced
      glutathione (GSH) production, inhibited cell apoptosis, and increased the gene
      expressions of SIRT1, AKT2, and Polg2. Importantly, the endogenously occurring
      melatonin of cumulus-oocyte complexes was significantly induced by HS. The
      results indicated that melatonin application effectively protected the oocytes
      from HS. These observations warranted the further studies in vivo regarding to
      improve the reproductive activities of animals under the global warming
      environment. 

PMID- 26291612
TI  - Epithelial-Mesenchymal Transition in Kidney Tubular Epithelial Cells Induced by
      Globotriaosylsphingosine and Globotriaosylceramide.
AB  - Fabry disease is a lysosomal storage disorder caused by deficiency of alpha
      galactosidase A (alpha-gal A), which results in the deposition of
      globotriaosylceramide (Gb3) in the vascular endothelium. Globotriaosylsphingosine
      (lyso-Gb3), a deacylated Gb3, is also increased in the plasma of patients with
      Fabry disease. Renal fibrosis is a key feature of advanced Fabry disease
      patients. Therefore, we evaluated the association of Gb3 and lyso-Gb3
      accumulation and the epithelial-mesenchymal transition (EMT) on tubular
      epithelial cells of the kidney. In HK2 cells, exogenous treatments of Gb3 and
      lyso-Gb3 increased the expression of TGF-beta, EMT markers (N-cadherin and alpha
      SMA), and phosphorylation of PI3K/AKT, and decreased the expression of E
      cadherin. Lyso-Gb3, rather than Gb3, strongly induced EMT in HK2 cells. In the
      mouse renal mesangial cell line, SV40 MES 13 cells, Gb3 strongly induced
      phenotype changes. The EMT induced by Gb3 was inhibited by enzyme alpha-gal A
      treatment, but EMT induced by lyso-Gb3 was not abrogated by enzyme treatment.
      However, TGF-beta receptor inhibitor (TRI, SB525334) inhibited the activation of
      TGF-beta and EMT markers in HK2 cells with Gb3 and lyso-Gb3 treatments. This
      study suggested that increased plasma lyso-Gb3 has a crucial role in the
      development of renal fibrosis through the cell-specific induction of the EMT in
      Fabry disease, and that TRI treatment, alongside enzyme replacement therapy,
      could be a potential therapeutic option for patients with Fabry disease. 

PMID- 26291613
TI  - Evolutionary and Functional Analysis of Old World Primate TRIM5 Reveals the
      Ancient Emergence of Primate Lentiviruses and Convergent Evolution Targeting a
      Conserved Capsid Interface.
AB  - The widespread distribution of lentiviruses among African primates, and the lack
      of severe pathogenesis in many of these natural reservoirs, are taken as evidence
      for long-term co-evolution between the simian immunodeficiency viruses (SIVs) and
      their primate hosts. Evidence for positive selection acting on antiviral
      restriction factors is consistent with virus-host interactions spanning millions
      of years of primate evolution. However, many restriction mechanisms are not virus
      specific, and selection cannot be unambiguously attributed to any one type of
      virus. We hypothesized that the restriction factor TRIM5, because of its unique
      specificity for retrovirus capsids, should accumulate adaptive changes in a virus
      specific fashion, and therefore, that phylogenetic reconstruction of TRIM5
      evolution in African primates should reveal selection by lentiviruses closely
      related to modern SIVs. We analyzed complete TRIM5 coding sequences of 22 Old
      World primates and identified a tightly-spaced cluster of branch-specific
      adaptions appearing in the Cercopithecinae lineage after divergence from the
      Colobinae around 16 million years ago. Functional assays of both extant TRIM5
      orthologs and reconstructed ancestral TRIM5 proteins revealed that this cluster
      of adaptations in TRIM5 specifically resulted in the ability to restrict
      Cercopithecine lentiviruses, but had no effect (positive or negative) on
      restriction of other retroviruses, including lentiviruses of non-Cercopithecine
      primates. The correlation between lineage-specific adaptations and ability to
      restrict viruses endemic to the same hosts supports the hypothesis that
      lentiviruses closely related to modern SIVs were present in Africa and infecting
      the ancestors of Cercopithecine primates as far back as 16 million years ago, and
      provides insight into the evolution of TRIM5 specificity. 

PMID- 26291615
TI  - Response to Benoist et al.: Pathological response to preoperative chemotherapy
      without pelvic irradiation in locally advanced rectal cancer.

PMID- 26291614
TI  - Plant Size as Determinant of Species Richness of Herbivores, Natural Enemies and
      Pollinators across 21 Brassicaceae Species.
AB  - Large plants are often more conspicuous and more attractive for associated
      animals than small plants, e.g. due to their wider range of resources. Therefore,
      plant size can positively affect species richness of associated animals, as shown
      for single groups of herbivores, but studies usually consider intraspecific size
      differences of plants in unstandardised environments. As comprehensive tests of
      interspecific plant size differences under standardised conditions are missing so
      far, we investigated effects of plant size on species richness of all associated
      arthropods using a common garden experiment with 21 Brassicaceae species covering
      a broad interspecific plant size gradient from 10 to 130 cm height. We recorded
      plant associated ecto- and endophagous herbivores, their natural enemies and
      pollinators on and in each aboveground plant organ, i.e. flowers, fruits, leaves
      and stems. Plant size (measured as height from the ground), the number of
      different plant organ entities and their biomass were assessed. Increasing plant
      size led to increased species richness of associated herbivores, natural enemies
      and pollinating insects. This pattern was found for ectophagous and endophagous
      herbivores, their natural enemies, as well as for herbivores associated with
      leaves and fruits and their natural enemies, independently of the additional
      positive effects of resource availability (i.e. organ biomass or number of
      entities and, regarding natural enemies, herbivore species richness). We found a
      lower R2 for pollinators compared to herbivores and natural enemies, probably
      caused by the high importance of flower characteristics for pollinator species
      richness besides plant size. Overall, the increase in plant height from 10 to 130
      cm led to a 2.7-fold increase in predicted total arthropod species richness. In
      conclusion, plant size is a comprehensive driver of species richness of the plant
      associated arthropods, including pollinators, herbivores and their natural
      enemies, whether they are endophagous or ectophagous or associated with leaves or
      fruits. 

PMID- 26291616
TI  - Nitrate Accumulation and Leaching in Surface and Ground Water Based on Simulated
      Rainfall Experiments.
AB  - To evaluate the process of nitrate accumulation and leaching in surface and
      ground water, we conducted simulated rainfall experiments. The experiments were
      performed in areas of 5.3 m2 with bare slopes of 3 degrees  that were treated
      with two nitrogen fertilizer inputs, high (22.5 g/m2 NH4NO3) and control (no
      fertilizer), and subjected to 2 hours of rainfall, with. From the 1st to the 7th
      experiments, the same content of fertilizer mixed with soil was uniformly applied
      to the soil surface at 10 minutes before rainfall, and no fertilizer was applied
      for the 8th through 12th experiments. Initially, the time-series nitrate
      concentration in the surface flow quickly increased, and then it rapidly
      decreased and gradually stabilized at a low level during the fertilizer
      experiments. The nitrogen loss in the surface flow primarily occurred during the
      first 18.6 minutes of rainfall. For the continuous fertilizer experiments, the
      mean nitrate concentrations in the groundwater flow remained at less than 10 mg/L
      before the 5th experiment, and after the 7th experiment, these nitrate
      concentrations were greater than 10 mg/L throughout the process. The time-series
      process of the changing concentration in the groundwater flow exhibited the same
      parabolic trend for each fertilizer experiment. However, the time at which the
      nitrate concentration began to change lagged behind the start time of groundwater
      flow by approximately 0.94 hours on average. The experiments were also performed
      with no fertilizer. In these experiments, the mean nitrate concentration of
      groundwater initially increased continuously, and then, the process exhibited the
      same parabolic trend as the results of the fertilization experiments. The nitrate
      concentration decreased in the subsequent experiments. Eight days after the 12
      rainfall experiments, 50.53% of the total nitrate applied remained in the
      experimental soil. Nitrate residues mainly existed at the surface and in the
      bottom soil layers, which represents a potentially more dangerous pollution
      scenario for surface and ground water. The surface and subsurface flow would
      enter into and contaminate water bodies, thus threatening the water environment. 

PMID- 26291617
TI  - Ovulation Prevalence in Women with Spontaneous Normal-Length Menstrual Cycles - A
      Population-Based Cohort from HUNT3, Norway.
AB  - BACKGROUND: Ovulatory menstrual cycles are essential for women's fertility and
      needed to prevent bone loss. There is a medical/cultural expectation that
      clinically normal menstrual cycles are inevitably ovulatory. Currently within the
      general population it is unknown the proportion of regular, normal-length
      menstrual cycles that are ovulatory. Thus, the objective of this study was to
      determine the population point prevalence of ovulation in premenopausal, normally
      menstruating women. The null hypothesis was that such cycles are ovulatory.
      METHODS: This is a single-cycle, cross-sectional, population-based study-a sub
      study of the HUNT3 health study in the semi-rural county (Nord Trondelag) in mid
      Norway. Participants included >3,700 spontaneously (no hormonal contraception)
      menstruating women, primarily Caucasian, ages 20-49.9 from that county.
      Participation rate was 51.9%. All reported the date previous flow started. A
      single, random serum progesterone level was considered ovulatory if >=9.54 nmol/L
      on cycle days 14 to -3 days before usual cycle length (CL). RESULTS: Ovulation
      was assessed in 3,168 women mean age 41.7 (interquartile range, [IQR] 36.8 to
      45.5), cycle length 28 days (d) (IQR 28 to 28) and body mass index (BMI) 26.3
      kg/m2 (95% CI 26.1 to 26.4). Parity was 95.6%, 30% smoked, 61.3% exercised
      regularly and 18% were obese. 1,545 women with a serum progesterone level on
      cycle days 14 to -3 were presumed to be in the luteal phase. Of these, 63.3% of
      women had an ovulatory cycle (n = 978) and 37% (n = 567) were anovulatory. Women
      with/ without ovulation did not differ in age, BMI, cycle day, menarche age,
      cigarette use, physical activity, % obesity or self-reported health. There were
      minimal differences in parity (96.7% vs. 94.5%, P = 0.04) and major differences
      in progesterone level (24.5 vs. 3.8 nmol/L, P = 0.001). CONCLUSION: Anovulation
      in a random population occurs in over a third of clinically normal menstrual
      cycles.

PMID- 26291619
TI  - Knotting fingerprints resolve knot complexity and knotting pathways in ideal
      knots.
AB  - We use disk matrices to define knotting fingerprints that provide fine-grained
      insights into the local knotting structure of ideal knots. These knots have been
      found to have spatial properties that highly correlate with those of interesting
      macromolecules. From this fine structure and an analysis of the associated planar
      graph, one can define a measure of knot complexity using the number of
      independent unknotting pathways from the global knot type as the knot is trimmed
      progressively to a short arc unknot. A specialization of the Cheeger constant
      provides a measure of constraint on these independent unknotting pathways.
      Furthermore, the structure of the knotting fingerprint supports a comparison of
      the tight knot pathways to the unconstrained unknotting pathways of comparable
      length. 

PMID- 26291618
TI  - Anti-Inflammatory Effects of Ang-(1-7) in Ameliorating HFD-Induced Renal Injury
      through LDLr-SREBP2-SCAP Pathway.
AB  - The angiotensin converting enzyme 2-angiotensin-(1-7)-Mas axis (ACE2-Ang-(1-7)
      Mas axis) is reported to participate in lipid metabolism in kidney, but its
      precise effects and underlying mechanisms remain unknown. We hypothesized that
      Ang-(1-7) reduces lipid accumulation and improves renal injury through the low
      density lipoprotein receptor-sterol regulatory element binding proteins 2-SREBP
      cleavage activating protein (LDLr-SREBP2-SCAP) system by suppressing inflammation
      in high fat diet (HFD)-fed mice. In this study, male C57BL/6 mice were randomized
      into four groups: STD (standard diet)+saline, HFD+saline, HFD+Ang-(1-7) and
      STD+Ang-(1-7). After 10 weeks of feeding, mice were administered Ang-(1-7) or
      saline for two weeks. We found that high inflammation status induced by HFD
      disrupted the LDLr-SREBP2-SCAP feedback system. Treatment of mice fed a high-fat
      diet with Ang-(1-7) induced significant improvement in inflammatory status,
      following the downregulation of LDLr, SREBP2 and SCAP, and then, decreased lipid
      deposition in kidney and improved renal injury. In conclusion, the anti
      inflammatory effect of Ang-(1-7) alleviates renal injury triggered by lipid
      metabolic disorders through a LDLr- SREBP2-SCAP pathway. 

PMID- 26291620
TI  - Third Wave of Influenza A(H7N9) Virus from Poultry, Guangdong Province, China,
      2014-2015.
AB  - Fourteen influenza A(H7N9) viruses were isolated from poultry or the environment
      in live poultry markets in Guangdong Province, China during 2014-2015.
      Phylogenetic analysis showed that all viruses were descended from viruses of the
      second wave of influenza A(H7N9) virus infections during 2013. These viruses can
      be divided into 2 branches. 

PMID- 26291621
TI  - Direct observation of drops on slippery lubricant-infused surfaces.
AB  - For a liquid droplet to slide down a solid planar surface, the surface usually
      has to be tilted above a critical angle of approximately 10 degrees . By
      contrast, droplets of nearly any liquid "slip" on lubricant-infused textured
      surfaces - so termed slippery surfaces - when tilted by only a few degrees. The
      mechanism of how the lubricant alters the static and dynamic properties of the
      drop remains elusive because the drop-lubricant interface is hidden. Here, we
      image the shape of drops on lubricant-infused surfaces by laser scanning confocal
      microscopy. The contact angle of the drop-lubricant interface with the substrate
      exceeds 140 degrees , although macroscopic contour images suggest angles as low
      as 60 degrees . Confocal microscopy of moving drops reveals fundamentally
      different processes at the front and rear. Drops recede via discrete depinning
      events from surface protrusions at a defined receding contact angle, whereas the
      advancing contact angle is 180 degrees . Drops slide easily, as the apparent
      contact angles with the substrate are high and the drop-lubricant interfacial
      tension is typically lower than the drop-air interfacial tension. Slippery
      surfaces resemble superhydrophobic surfaces with two main differences: drops on a
      slippery surface are surrounded by a wetting ridge of adjustable height and the
      air underneath the drop in the case of a superhydrophobic surface is replaced by
      lubricant in the case of a slippery surface. 

PMID- 26291622
TI  - Hot Off the Press: B-lines and Focused Lung Ultrasound to Diagnose Acute Heart
      Failure in Dyspneic Patients.

PMID- 26291623
TI  - Resonance Raman Spectroscopy of the T1 Triplet Excited State of Oligothiophenes.
AB  - The characterization of triplet excited states is essential for research on
      organic photovoltaics and singlet fission. We report resonance Raman spectra of
      two triplet oligothiophenes with n-alkyl substituents, a tetramer and hexamer.
      The spectra of the triplets are more complex than the ground state, and we find
      that density functional theory calculations are a useful starting point for
      characterizing the bands. The spectra of triplet tetrathiophene and hexathiophene
      differ significantly from one another. This observation is consistent with a T1
      excitation that is delocalized over at least five rings in long oligomers. Bands
      in the 500-800 cm(-1) region are greatly diminished for an aggregated sample of
      hexathiophene, likely caused by fast electronic dephasing. These experiments
      highlight the potential of resonance Raman spectroscopy to unequivocally detect
      and characterize triplets in thiophene materials. The vibrational spectra can
      also serve as rigorous standards for evaluating computational methods for excited
      state molecules. 

PMID- 26291624
TI  - DNA Extraction Method Affects the Detection of a Fungal Pathogen in Formalin
      Fixed Specimens Using qPCR.
AB  - Museum collections provide indispensable repositories for obtaining information
      about the historical presence of disease in wildlife populations. The pathogenic
      amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd) has played a
      significant role in global amphibian declines, and examining preserved specimens
      for Bd can improve our understanding of its emergence and spread. Quantitative
      PCR (qPCR) enables Bd detection with minimal disturbance to amphibian skin and is
      significantly more sensitive to detecting Bd than histology; therefore,
      developing effective qPCR methodologies for detecting Bd DNA in formalin-fixed
      specimens can provide an efficient and effective approach to examining historical
      Bd emergence and prevalence. Techniques for detecting Bd in museum specimens have
      not been evaluated for their effectiveness in control specimens that mimic the
      conditions of animals most likely to be encountered in museums, including those
      with low pathogen loads. We used American bullfrogs (Lithobates catesbeianus) of
      known infection status to evaluate the success of qPCR to detect Bd in formalin
      fixed specimens after three years of ethanol storage. Our objectives were to
      compare the most commonly used DNA extraction method for Bd (PrepMan, PM) to
      Macherey-Nagel DNA FFPE (MN), test optimizations for Bd detection with PM, and
      provide recommendations for maximizing Bd detection. We found that successful
      detection is relatively high (80-90%) when Bd loads before formalin fixation are
      high, regardless of the extraction method used; however, at lower infection
      levels, detection probabilities were significantly reduced. The MN DNA extraction
      method increased Bd detection by as much as 50% at moderate infection levels. Our
      results indicate that, for animals characterized by lower pathogen loads (i.e.,
      those most commonly encountered in museum collections), current methods may
      underestimate the proportion of Bd-infected amphibians. Those extracting DNA from
      archived museum specimens should ensure that the techniques they are using are
      known to provide high-quality throughput DNA for later analysis. 

PMID- 26291625
TI  - Bacillus anthracis Diversity and Geographic Potential across Nigeria, Cameroon
      and Chad: Further Support of a Novel West African Lineage.
AB  - Zoonoses, diseases affecting both humans and animals, can exert tremendous
      pressures on human and veterinary health systems, particularly in resource
      limited countries. Anthrax is one such zoonosis of concern and is a disease
      requiring greater public health attention in Nigeria. Here we describe the
      genetic diversity of Bacillus anthracis in Nigeria and compare it to Chad,
      Cameroon and a broader global dataset based on the multiple locus variable number
      tandem repeat (MLVA-25) genetic typing system. Nigerian B. anthracis isolates had
      identical MLVA genotypes and could only be resolved by measuring highly mutable
      single nucleotide repeats (SNRs). The Nigerian MLVA genotype was identical or
      highly genetically similar to those in the neighboring countries, confirming the
      strains belong to this unique West African lineage. Interestingly, sequence data
      from a Nigerian isolate shares the anthrose deficient genotypes previously
      described for strains in this region, which may be associated with vaccine
      evasion. Strains in this study were isolated over six decades, indicating a high
      level of temporal strain stability regionally. Ecological niche models were used
      to predict the geographic distribution of the pathogen for all three countries.
      We describe a west-east habitat corridor through northern Nigeria extending into
      Chad and Cameroon. Ecological niche models and genetic results show B. anthracis
      to be ecologically established in Nigeria. These findings expand our
      understanding of the global B. anthracis population structure and can guide
      regional anthrax surveillance and control planning. 

PMID- 26291627
TI  - Reliable Change Estimates for Assessing Recovery From Concussion Using the ANAM4
      TBI-MIL.
AB  - OBJECTIVE: To establish the reliable change parameters for the Automated
      Neuropsychological Assessment Metrics (ANAM) using a healthy normative sample of
      active duty service members (SMs) and apply the parameters to sample of recently
      deployed SMs. METHODS: Postdeployment neurocognitive performance was compared in
      1893 US Marines with high rates of combat exposure during deployment. Of the
      sample, 289 SMs had data for 2 predeployment assessments and were used as a
      normative subsample and 502 SMs had data for predeployment and postdeployment
      assessments and were used as a deployed subsample. On the basis of self-report,
      the deployed subsample were further classified as concussed (n = 238) or as
      nonconcussed controls (n = 264). Reliable change parameters were estimated from
      the normative sample and applied data for both deployed groups. Postdeployment
      performance was quantified using a general linear model (2 group * 2 time)
      multivariate analysis of variance with repeated measures. RESULTS: Both deployed
      groups demonstrated a pattern of meaningful decreases in performance over time.
      CONCLUSIONS: Information from this effort, specifically the reliable change
      parameters and the base rates of reliable decline, can be used to assist with the
      identification of postdeployment cognitive issues.

PMID- 26291628
TI  - Self-Reported Traumatic Brain Injury, Health and Rate of Chronic Multisymptom
      Illness in Veterans From the 1990-1991 Gulf War.
AB  - BACKGROUND: Traumatic brain injury (TBI) was not considered to be common in the
      1990-1991 Gulf War (GW). Therefore, the relationship between TBI and chronic
      health symptoms experienced by GW veterans is unknown. Health symptoms reported
      by veterans deployed more recently to this region (Operations Enduring and Iraqi
      Freedom) are similar to those of GW veterans and have been primarily attributed
      to TBI. OBJECTIVE: To examine the relationships among self-reported TBI, health
      symptoms, chronic multisymptom illness (CMI), and health-related quality of life
      among GW veterans. PARTICIPANTS: Participants included 1 274 GW veterans from the
      Devens Cohort Study, 156 of whom self-reported a history of TBI (12.2% of the
      sample). DESIGN: Cross-sectional retrospective analysis of existing survey data.
      MAIN MEASURES: A 52-item health symptom checklist and the RAND 36-Item Health
      short Form Survey. RESULTS: Self-reported TBI in GW Veterans is related to
      increased rates of health symptoms, CMI, and poorer health-related quality of
      life. CONCLUSIONS: Gulf War veterans' self-reported exposure to TBI is related to
      increased rates of chronic health symptoms and CMI, which interfere with everyday
      activities of daily living.

PMID- 26291626
TI  - Detection and Tracking of NY-ESO-1-Specific CD8+ T Cells by High-Throughput T
      Cell Receptor beta (TCRB) Gene Rearrangements Sequencing in a Peptide-Vaccinated
      Patient.
AB  - Comprehensive immunological evaluation is crucial for monitoring patients
      undergoing antigen-specific cancer immunotherapy. The identification and
      quantification of T cell responses is most important for the further development
      of such therapies. Using well-characterized clinical samples from a high
      responder patient (TK-f01) in an NY-ESO-1f peptide vaccine study, we performed
      high-throughput T cell receptor beta-chain (TCRB) gene next generation sequencing
      (NGS) to monitor the frequency of NY-ESO-1-specific CD8+ T cells. We compared
      these results with those of conventional immunological assays, such as IFN-gamma
      capture, tetramer binding and limiting dilution clonality assays. We sequenced
      human TCRB complementarity-determining region 3 (CDR3) rearrangements of two NY
      ESO-1f-specific CD8+ T cell clones, 6-8L and 2F6, as well as PBMCs over the
      course of peptide vaccination. Clone 6-8L possessed the TCRB CDR3 gene TCRBV11
      03*01 and BJ02-01*01 with amino acid sequence CASSLRGNEQFF, whereas 2F6 possessed
      TCRBV05-08*01 and BJ02-04*01 (CASSLVGTNIQYF). Using these two sequences as
      models, we evaluated the frequency of NY-ESO-1-specific CD8+ T cells in PBMCs ex
      vivo. The 6-8L CDR3 sequence was the second most frequent in PBMC and was present
      at high frequency (0.7133%) even prior to vaccination, and sustained over the
      course of vaccination. Despite a marked expansion of NY-ESO-1-specific CD8+ T
      cells detected from the first through 6th vaccination by tetramer staining and
      IFN-gamma capture assays, as evaluated by CDR3 sequencing the frequency did not
      increase with increasing rounds of peptide vaccination. By clonal analysis using
      12 day in vitro stimulation, the frequency of B*52:01-restricted NY-ESO-1f
      peptide-specific CD8+ T cells in PBMCs was estimated as only 0.0023%, far below
      the 0.7133% by NGS sequencing. Thus, assays requiring in vitro stimulation might
      be underestimating the frequency of clones with lower proliferation potential.
      High-throughput TCRB sequencing using NGS can potentially better estimate the
      actual frequency of antigen-specific T cells and thus provide more accurate
      patient monitoring. 

PMID- 26291629
TI  - Evaluating the Psychometric Properties of 3 Depression Measures in a Sample of
      Persons With Traumatic Brain Injury and Major Depressive Disorder.
AB  - OBJECTIVES: To explore the psychometric properties of 3 widely used measures of
      depression in a sample of individuals with traumatic brain injury (TBI) and major
      depressive disorder and refine them to maximize efficiency. DESIGN: Secondary
      analysis of data from a randomized controlled trial of cognitive-behavioral
      therapy for depression after TBI. SETTING: Nationwide recruitment from community
      and clinical settings. PARTICIPANTS: One hundred adults within 10 years of
      complicated mild to severe TBI. INTERVENTION: Telephone and in-person cognitive
      behavioral therapy. MAIN MEASURES: Patient Health Questionnaire-9 (PHQ-9),
      Symptom Checklist-20, and Hamilton Depression Rating Scale. RESULTS: We used
      Rasch rating scale analysis and multilevel modeling to investigate the 3
      measures. Measurement properties of each of the depression measures were strong.
      We explored modifications to the rating scales to improve efficiency while
      retaining strong psychometric characteristics. Correlations among these revised
      measures were high. Treatment effects of each revised depression measure were
      compared using a multilevel model, and effect size estimates were comparable
      among the revised PHQ-9, Symptom Checklist-20, and Hamilton Depression Rating
      Scale. CONCLUSIONS: Although each of the 3 measures demonstrated adequate
      reliability, the efficiency of all 3 instruments was improved with rating scale
      analysis. The PHQ-9 required the fewest modifications and functions well as a
      measure of depression among those with TBI.

PMID- 26291630
TI  - Return to Physical Activity Timing and Dual-Task Gait Stability Are Associated 2
      Months Following Concussion.
AB  - OBJECTIVE: The effect of physical activity resumption on functional recovery
      following concussion is poorly understood. We sought to examine the relationship
      between physical activity resumption timing and gait stability 2 months following
      concussion. SETTING: Motion analysis laboratory. PARTICIPANTS: Twenty-nine
      individuals who sustained a concussion and were subsequently allowed to return to
      preinjury levels of physical activity within 2 months postinjury. DESIGN:
      Prospective cohort study. MAIN MEASURES: The return-to-activity day (RTA-day) was
      identified as the first day postinjury that each participant was medically
      cleared to resume regular physical activity. Whole-body center-of-mass (COM)
      motion during single-task and dual-task walking was assessed 2 months postinjury.
      Correlation coefficients were calculated between the RTA-day and single/dual-task
      gait stability as well as symptom severity measurements 2 months postinjury.
      RESULTS: Dual-task medial-lateral COM displacement (r = -0.52, P = .004) and peak
      medial-lateral COM velocity (r = -0.37, P = .048) were significantly correlated
      with RTA-day. Dual-task peak forward velocity and single-task gait stability
      measures were not significantly correlated with RTA-day. CONCLUSIONS: The time of
      RTA-day clearance, within a 2 months postinjury period, is significantly
      correlated with dual-task medial-lateral gait stability measured at the end of
      that period, suggesting that frontal plane gait stability recovery is sensitive
      to the timing of RTA-day.

PMID- 26291631
TI  - Measurement Error in the Immediate Postconcussion Assessment and Cognitive
      Testing (ImPACT): Systematic Review.
AB  - OBJECTIVE: To review the literature on the reliability of the Immediate Post
      Concussion Assessment and Cognitive Testing (ImPACT). DESIGN: Systematic review
      of the relevant literature in PubMed, CINAHL, and PSYCHINFO. Studies were
      evaluated using the STROBE instrument and custom developed items. RESULTS: Search
      yielded 5 943 articles. Ten studies met the inclusion criteria and were reviewed.
      With the exception of processing speed, all composite scores consistently
      exhibited poor to moderate reliability (ie, intraclass correlation coefficient
      <0.80). When considering 2 time points, participants who were misclassified as
      experiencing a "reliable change" in any score ranged between 5% and 26% for
      verbal memory, 2.2% and 19.6% for visual memory, 4% and 24% for processing speed,
      and 4% and 23.2% for reaction time. CONCLUSIONS: The Pearson r correlation
      coefficient and average measures intraclass correlation coefficient may be
      inappropriately utilized to examine the reliability of ImPACT scores. Given the
      poor to moderate reliability of most ImPACT scores, clinicians should be cautious
      when ImPACT is used as a criterion for medical clearance to return to play after
      concussion. Because of its widespread use in concussion-related clinical
      research, researchers must exercise due diligence when utilizing ImPACT to
      evaluate outcomes after concussion or to validate other outcome measures.

PMID- 26291632
TI  - Oculomotor-Based Vision Assessment in Mild Traumatic Brain Injury: A Systematic
      Review.
AB  - OBJECTIVE: The purpose of this article is to synthesize and appraise the evidence
      regarding the use of oculomotor-based vision assessment to identify and monitor
      recovery from mild traumatic brain injury (mTBI). Specific objectives are to (1)
      identify changes in oculomotor-based vision following mTBI; (2) distinguish
      methods of assessment; (3) appraise the level and quality of evidence; and, if
      warranted, (4) determine clinical recommendations for assessment. METHODS: A
      systematic review was undertaken to identify and appraise relevant literature. A
      search was conducted of 7 databases of peer-reviewed literature from January 1990
      to January 2015. Articles were included if study populations were clearly
      identified as having mTBI and used an assessment of oculomotor-based vision.
      Articles with pooled data (eg, mTBI and stroke), addressing afferent visual
      function (eg, visual field deficits) or using single case designs, were excluded.
      RESULTS: Twenty articles were selected for inclusion. Exploratory findings
      suggest that measurements of saccades, smooth pursuit, and vergence are useful in
      detecting changes associated with mTBI. Assessment methods included eye tracker
      protocols, optometric assessment, and the King-Devick test. CONCLUSION: The
      strength of this evidence is not yet sufficient to warrant clinical
      recommendations. Research using rigorous methods is required to develop reliable,
      valid, and clinically useful assessment protocols.

PMID- 26291633
TI  - The Community Balance and Mobility Scale: A Pilot Study Detecting Impairments in
      Military Service Members With Comorbid Mild TBI and Psychological Health
      Conditions.
AB  - OBJECTIVE: To compare the capacity of the Community Balance and Mobility Scale
      (CB&M) to identify balance and mobility deficits in Service Members (SMs) with
      mild traumatic brain injury and comorbid psychological health conditions
      (mTBI/PH) to other commonly used balance assessments. SETTING: A clinical
      research institute that provides a 4-week, outpatient, interdisciplinary program
      for active-duty SMs with mTBI/PH. DESIGN: A nonrandomized, cross-sectional design
      that compared multiple measures between 2 groups-active duty SMs with (n = 8) and
      without (n = 8) the dual diagnosis of mTBI/PH. MAIN MEASURES: Gait speed,
      Activities-specific Balance Confidence scale (ABC), Functional Gait Assessment
      (FGA), and CB&M to assess functional balance among the community-dwelling, TBI
      population. RESULTS: Across all measures, the mTBI/PH group performed
      significantly worse (P <= .01) with the exception of the FGA. The abilities of
      all objective measures to distinguish participants with mTBI/PH from healthy
      controls ranged from fair to excellent (area under the curve [AUC] = 0.66-0.94).
      However, the CB&M showed the largest group differences in effect size (d = 2.6)
      and had the highest discriminate ability (AUC = 0.98; sensitivity 100%;
      specificity 88%). CONCLUSION: The CB&M appears to have higher sensitivity and
      specificity than other measures of balance in SMs with mTBI/PH. A higher cut
      score for the CB&M is needed for this population.

PMID- 26291634
TI  - Therapy Online: A Web-Based Video Support Group for Family Caregivers of
      Survivors With Traumatic Brain Injury.
AB  - OBJECTIVE: This innovative descriptive study explores the benefits of a traumatic
      brain injury (TBI) caregiver support group intervention provided using
      videoconferencing within a password protected Web-based platform. METHODS: Ten
      caregivers of family members with TBI were registered to a password-protected Web
      site (Caring for Others) that provided information about caring for a person with
      TBI and access to a videoconferencing support group intervention program. Where
      needed, caregivers were provided with computer equipment, Internet access, and
      training to negotiate the Web site links. Two groups of 5 caregivers of survivors
      of TBI participated (average age of survivor-20 years, average time since injury
      4.6 years) and met online with a trained clinician weekly for 10 sessions. Using
      directed content analysis, transcripts of each session were coded with NVivo
      software. RESULTS: The content analysis reported group process themes,
      therapeutic interventions used, caregiver outcomes, and the challenges for
      clinicians delivering a therapeutic intervention online. CONCLUSIONS: Traumatic
      brain injury caregivers shared similar concerns and problem-solving strategies
      for managing caregiving tasks. Overall, participants found the sessions helpful
      for managing the emotional impact of caring for a family member with TBI.

PMID- 26291635
TI  - Evidence-Based Practice for the Use of Internal Strategies as a Memory
      Compensation Technique After Brain Injury: A Systematic Review.
AB  - OBJECTIVE: To complete a systematic review of internal memory strategy use with
      people who have brain injury and provide practitioners with information that will
      impact their clinical work. METHODS: A systematic literature search to identify
      published intervention studies that evaluated an internal memory strategy or
      technique to improve memory function of individuals with brain injury. Relevant
      data from reviewed articles were coded using 4 clinical questions targeting
      participants, interventions, research methods, and outcomes. RESULTS: A
      comprehensive search identified 130 study citations and abstracts. Forty-six met
      inclusion/exclusion criteria and were systematically reviewed. Visual imagery was
      most frequently studied, in isolation or in combination with other internal
      strategies. Despite significant variability in research methods and outcomes
      across studies, the evidence provides impetus for use of internal memory
      strategies with individuals following brain injury. CONCLUSIONS: Individuals with
      traumatic brain injury may benefit from internal memory strategy use, and
      clinicians should consider internal memory strategy instruction as part of
      intervention plans. Further research needs to better delineate influences on
      intervention candidacy and outcomes.

PMID- 26291636
TI  - (+)- and (-)-Pestaloxazine A, a Pair of Antiviral Enantiomeric Alkaloid Dimers
      with a Symmetric Spiro[oxazinane-piperazinedione] Skeleton from Pestalotiopsis
      sp.
AB  - A pair of new enantiomeric alkaloid dimers, (+)- and (-)-pestaloxazine A (1),
      with an unprecedented symmetric spiro[oxazinane-piperazinedione] skeleton,
      consisting of 22 carbons and 12 heteroatoms, were isolated from a Pestalotiopsis
      sp. fungus derived from a soft coral. Separation of the enantiomeric alkaloid
      dimers was achieved by chiral HPLC. Their structures including absolute
      configurations were elucidated on the basis of a comprehensive analysis of their
      spectroscopic and X-ray diffraction data and CD calculations. (+)-Pestaloxazine A
      exhibited potent antiviral activity against EV71 with an IC50 value of 14.2 +/-
      1.3 MUM, which was stronger than that of the positive control ribavirin (IC50 =
      256.1 +/- 15.1 MUM). 

PMID- 26291637
TI  - Size characterization and quantification of exosomes by asymmetrical-flow field
      flow fractionation.
AB  - In the past few years extracellular vesicles called exosomes have gained huge
      interest of scientific community since they show a great potential for human
      diagnostic and therapeutic applications. However, an ongoing challenge is
      accurate size characterization and quantification of exosomes because of the lack
      of reliable characterization techniques. In this work, the emphasis was focused
      on a method development to size-separate, characterize, and quantify small
      amounts of exosomes by asymmetrical-flow field-flow fractionation (AF4) technique
      coupled to a multidetection system (UV and MALS). Batch DLS (dynamic light
      scattering) and NTA (nanoparticle tracking analysis) analyses of unfractionated
      exosomes were also conducted to evaluate their shape and internal structure, as
      well as their number density. The results show significant influence of cross
      flow conditions and channel thickness on fractionation quality of exosomes,
      whereas the focusing time has less impact. The AF4/UV-MALS and DLS results
      display the presence of two particles subpopulations, that is, the larger
      exosomes and the smaller vesicle-like particles, which coeluted in AF4 together
      with impurities in early eluting peak. Compared to DLS and AF4-MALS results, NTA
      somewhat overestimates the size and the number density for larger exosome
      population, but it discriminates the smaller particle population. 

PMID- 26291638
TI  - Emerging Infections Program as Surveillance for Antimicrobial Drug Resistance.
AB  - Across the United States, antimicrobial drug-resistant infections affect a
      diverse population, and effective interventions require concerted efforts across
      various public health and clinical programs. Since its onset in 1994, the Centers
      for Disease Control and Prevention Emerging Infections Program has provided
      robust and timely data on antimicrobial drug-resistant infections that have been
      used to inform public health action across a spectrum of partners with regard to
      many highly visible antimicrobial drug-resistance threats. These data span
      several activities within the Program, including respiratory bacterial
      infections, health care-associated infections, and some aspects of foodborne
      diseases. These data have contributed to estimates of national burden, identified
      populations at risk, and determined microbiological causes of infection and their
      outcomes, all of which have been used to inform national policy and guidelines to
      prevent antimicrobial drug-resistant infections. 

PMID- 26291639
TI  - Generation, Characterization, and Reactivity of a Cu(II)-Alkylperoxide/Anilino
      Radical Complex: Insight into the O-O Bond Cleavage Mechanism.
AB  - The reaction of [Cu(I)(TIPT3tren) (CH3CN)]ClO4 (1) and cumene hydroperoxide
      (C6H5C(CH3)2OOH, ROOH) at -60  degrees C in CH2Cl2 gave a Cu(II)
      alkylperoxide/anilino radical complex 2, the formation of which was confirmed by
      UV-vis, resonance Raman, EPR, and CSI-mass spectroscopy. The mechanism of
      formation of 2, as well as its reactivity, has been explored. 

PMID- 26291640
TI  - Introduction of Julian F. Hillyer, Recipient of the Henry Baldwin Ward Medal For
      2015.

PMID- 26291641
TI  - Standing from the Floor in Community-Dwelling Older Adults.
AB  - While considerable research has targeted physical performance in older adults,
      less is known about the ability to rise from the floor among community-dwelling
      elders. The purposes of the study were to (1) examine physical performance
      correlates of timed supine to stand performance and (2) identify the predominant
      motor pattern used to complete floor rise. Fifty-three community-dwelling adults
      over the age of 60 (x = 78.5 +/- 8.5; 36 [68%] females) performed a timed supine
      to stand test and physical performance assessments. Forty-eight subjects (90.6%)
      demonstrated an initial roll with asymmetrical squat sequence when rising to
      stand. Supine to stand performance time was significantly correlated with all
      physical performance tests, including gait speed (r = -.61; p < .001), grip
      strength (r = -.30; p < .05), and Timed Up and Go (TUG) performance (r = .71; p <
      .001). Forty-eight percent of the variance in rise time (p < .001) was attributed
      to TUG velocity. Findings serve to enhance both functional performance assessment
      and floor rise interventions. 

PMID- 26291643
TI  - Evaluation of the Acute Toxicity, Cytotoxicity, and Genotoxicity of Chresta
      martii (Asteraceae).
AB  - Chresta martii (Asteraceae), found in the Xingo region, northeastern Brazil, is
      used in the treatment of gastrointestinal (GIT) and liver disorders and malaria.
      However, there are few studies regarding efficacy and safety of use for this
      species. Thus, the objective of this study was to determine in vivo acute
      toxicity and in vitro cytotoxicity of organic extracts of C. martii as well as in
      vivo genotoxicity of its semipurified fraction. Dried aerial parts of C. martii
      were extracted using three organic solvents (cyclohexane [ECCm], ethyl acetate
      [EACm], and ethanol [EECm]), and these extracts were examined for acute toxicity
      (50-2000 mg/kg ip or po) and cytotoxicity (50 MUg/ml) in carcinogenic human cell
      lines (HL-60, NCIH-292, and MCF-7). The EACm, which showed evidence of toxicity
      (in vivo and in vitro), was fractionated on a silica column, yielding four
      fractions (F1-F4). The F1 was utilized for genotoxicity (50 mg/kg ip), by in vivo
      micronucleus (MN) assay. ECCm showed no indication of acute toxicity or
      occurrence of death, while the LD50 estimated for the extracts (EACm and EECm)
      was 500 mg/kg po and 200 mg/kg ip. The EACm (50 MUg/ml) inhibited growth of tumor
      cells HL-60 (96.54%), NCIH-292 (73.43%), and MCF-7 (15%). The F1 fraction induced
      MN formation in polychromatic erythrocytes of Swiss Webster mice. Organic
      extracts from C. martii exhibited acute toxicity classified as mild to moderate,
      in addition to cytotoxicity (in vitro), while the F1 semipurified fraction
      induced genotoxicity (in vivo). 

PMID- 26291644
TI  - Telling stories and adding scores: Measuring resilience in young children
      affected by maternal HIV and AIDS.
AB  - "Telling stories and adding scores: Measuring resilience in young children
      affected by maternal HIV and AIDS", demonstrates how a concurrent mixed method
      design assisted cross-cultural comparison and ecological descriptions of
      resilience in young South African children, as well as validated alternative ways
      to measure resilience in young children. In a longitudinal randomised control
      trial, which investigated psychological resilience in mothers and children
      affected by HIV/AIDS, we combined a qualitative projective story-telling
      technique (Duss Fable) with quantitative data (Child Behaviour Checklist). The
      children mostly displayed adaptive resilience-related behaviours, although
      maladaptive behaviours were present. Participating children use internal
      (resolve/agency, positive future expectations, emotional intelligence) and
      external protective resources (material resources, positive institutions) to
      mediate adaptation. Children's maladaptive behaviours were exacerbated by
      internal (limited problem-solving skills, negative emotions) and external risk
      factors (chronic and cumulative adversity). 

PMID- 26291645
TI  - Anti-inflammatory tirucallane triterpenoids from Anopyxis klaineana Pierre
      (Engl.), (Rhizophoraceae).
AB  - Phytochemical investigation of the stem bark extract of Anopyxis klaineana was
      carried out by various chromatographic techniques resulting in the isolation and
      characterization of three new tirucallane triterpenoids, namely 3,23
      dioxotirucalla-7,24-dien-21-oic acid (1), 3,4-secotirucalla-23-oxo-4(28)7,24
      trien-3,21-dioic acid (2) and 3,4-secotirucalla-4-hydroxy-23-oxo-7,24-diene-3,21
      dioic acid-21-methyl ester (3), along with nine known compounds (4-12). The
      structural elucidation of the compounds was performed by means of high-resolution
      mass spectrometry (HRMS(n)), nuclear magnetic resonance (NMR), and by comparison
      to literature data. Although none of the isolated compounds showed antibacterial
      efficacy against selected environmental and clinically important pathogenic Gram
      positive and -negative bacteria, they demonstrated moderate DPPH free radical
      scavenging properties. Furthermore, compounds 1 and 7 exhibited remarkable anti
      inflammatory potential in a prostaglandin E2 (PGE2) competitive enzyme
      immunoassay with IC50 values of 3.63 MUM and 10.23 MUM, respectively.

PMID- 26291646
TI  - 19(4->3)-abeo-abietane diterpenoids from Scrophularia dentata Royle ex Benth.
AB  - Five 19(4->3)-abeo-abietane diterpenoids, scrodentoids A-E (1-5), were isolated
      from the whole plant of Scrophularia dentata. Planar structures of scrodentoids A
      E were elucidated mainly by using 1D, 2D NMR and MS data. The absolute
      configurations of compounds 1 and 2 were established using X-ray crystallographic
      analysis. The absolute configurations of other compounds were confirmed using
      HPLC-UV/CD detection. The immunosuppressive effects of compounds 1-5 were studied
      using a ConA-induced splenocyte proliferation model. These compounds
      significantly inhibited ConA-induced splenocyte proliferation, with IC50 values
      in the range of 3.49-133.86 MUM. Compounds 1-5 (IC50>10 MUM) showed no
      discernible cytotoxic activity against B16 or MCF-7 cells.

PMID- 26291647
TI  - The Effect of Smoking on Corneal Endothelial Cells.
AB  - PURPOSE: To investigate the effect of chronic cigarette smoking on the
      endothelial cells of the cornea via non-contact specular microscopy. METHOD: In
      this prospective, cross-sectional study, 25 eyes of 25 chronic smokers and 21
      eyes of 21 age-matched, healthy non-smokers were enrolled. The Fagerstrom Test
      for Nicotine Dependence on Cigarettes was used to determine the nicotine
      dependency level. The level of cotinine, a major metabolite of nicotine, was
      measured in urine samples from the control group to detect whether they were
      passively affected by cigarette smoke. All participants underwent measurement of
      tear break-up time (TBUT), central corneal thickness (CCT), and axial length.
      Endothelial cell density and endothelial cell morphology were evaluated by non
      contact specular microscopy. RESULTS: On average, the cigarette smokers consumed
      19.2 +/- 8.3 cigarettes per day and had been smoking for 14.5 +/- 6.8 years. The
      mean TBUT value was significantly lower in the smoker group compared to the non
      smoker group (p < 0.05). No statistically significant difference was found in the
      mean CCT, mean endothelial cell density, or parameters of endothelial cell
      morphology between smokers and non-smokers. CONCLUSION: This study showed that
      cigarette smoking seems to affect the TBUT value but no effects were found on the
      parameters of corneal endothelial cells.

PMID- 26291642
TI  - Vaccination of healthcare workers: A review.
AB  - Vaccine-preventable diseases are a significant cause of morbidity and mortality.
      As new vaccines are proving to be effective and as the incidence of some
      infections decreases, vaccination practices are changing. Healthcare workers
      (HCWs) are particularly exposed to and play a role in nosocomial transmission,
      which makes them an important target group for vaccination. Most vaccine
      preventable diseases still carry a significant risk of resurgence and have caused
      outbreaks in recent years. While many professional societies favor vaccination of
      HCWs as well as the general population, recommendations differ from country to
      country. In turn, vaccination coverage varies widely for each microorganism and
      for each country, making hospitals and clinics vulnerable to outbreaks. Vaccine
      mandates and non-mandatory strategies are the subject of ongoing research and
      controversies. Optimal approaches to increase coverage and turn the healthcare
      workforce into an efficient barrier against infectious diseases are still being
      debated. 

PMID- 26291648
TI  - Effect of e-Cigarette Use on Cough Reflex Sensitivity.
AB  - BACKGROUND: E-cigarettes (e-cigs) have attained widespread popularity, yet
      knowledge of their physiologic effects remains minimal. The aim of this study was
      to evaluate the effect of a single exposure to e-cig vapor on cough reflex
      sensitivity. METHODS: Thirty healthy nonsmokers underwent cough reflex
      sensitivity measurement using capsaicin cough challenge at baseline, 15 min, and
      24 h after e-cig exposure (30 puffs 30 s apart). The end point of cough challenge
      is the concentration of capsaicin inducing five or more coughs (C5). The number
      of coughs induced by each e-cig inhalation was counted. A subgroup of subjects (n
      = 8) subsequently underwent an identical protocol with a non-nicotine-containing
      e-cig. RESULTS: Cough reflex sensitivity was significantly inhibited (C5
      increased) 15 min after e-cig use (?0.29; 95% CI, ?0.43 to ?0.15; P < .0001); 24
      h later, C5 returned to baseline (0.24; 95% CI, 0.10-0.38; P = .0002 vs post-15
      min value). A subgroup of eight subjects demonstrating the largest degree of
      cough reflex inhibition had no suppression after exposure to a non-nicotine
      containing e-cig (P = .0078 for comparison of ?C5 after nicotine vs non-nicotine
      device). Furthermore, more coughing was induced by the nicotine-containing vs non
      nicotine-containing device (P = .0156). CONCLUSIONS: A single session of e-cig
      use, approximating nicotine exposure of one tobacco cigarette, induces
      significant inhibition of cough reflex sensitivity. Exploratory analysis of a
      subgroup of subjects suggests that nicotine is responsible for this observation.
      Our data, consistent with previous studies of nicotine effect, suggest a dual
      action of nicotine: an immediate, peripheral protussive effect and a delayed
      central antitussive effect. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02203162;
      URL: www.clinicaltrials.gov.

PMID- 26291649
TI  - Na(+)-H(+) exchanger inhibitor prevents early death in hereditary cardiomyopathy.
AB  - Using the UM-X7.1 hereditary cardiomyopathic and muscular dystrophy hamsters
      (HCMH), we tested the effects of lifelong preventive or curative treatments
      during the heart failure phase with the NHE-1 inhibitor EMD 87580 (EMD) or with
      the angiotensin-converting enzyme inhibitor cilazapril on the intracellular Na(+)
      and Ca(2+) overloads, elevated level of NHE-1, necrosis, hypertrophy, heart
      failure, and early death. Our results showed that 310-day pretreatment of 30-day
      old HCMHs with EMD significantly prevented cardiac necrosis, cardiomyocyte
      hypertrophy, and reduced the heart to body mass ratio. This treatment
      significantly prevented Na(+) and Ca(2+) overloads and the increase in NHE-1
      protein level observed in HCMHs. Importantly, this lifelong preventive treatment
      significantly decreased the levels of creatine kinase and prevented early death
      of HCMHs. Curative treatment of hypertrophic 275-day-old HCMHs for 85 days with
      EMD significantly prevented hypertrophy and early death of HCMHs. However,
      treatments with cilazapril did not have any significant effects on the cardiac
      parameters studied or on early death of HCMHs. Our results suggest that the
      increase in the NHE-1 level and the consequent Na(+) and Ca(2+) overloads are
      implicated in the pathological process leading to heart failure and early death
      in HCMHs, and treatment with the NHE-1 inhibitor is promising for preventing
      early death in hereditary cardiomyopathy. 

PMID- 26291650
TI  - Body mass index, physical activity and quality of life of ovarian cancer
      survivors: time to get moving?
AB  - OBJECTIVE: To evaluate the association between body mass index (BMI), physical
      activity (PA) and the quality of life (QoL) of ovarian cancer survivors. METHODS:
      We performed a two-centre cross-sectional study of women who had been treated for
      ovarian cancer between January 2007 and December 2014 at the Royal Cornwall
      Hospital Trust and the Plymouth Hospitals NHS Trust. QoL was assessed using the
      EORTC QLQ-C30 and QLQ-OV28 questionnaires, and PA using the Godin Leisure Time
      Exercise questionnaire. RESULTS: In total, 293 ovarian cancer survivors were
      invited to participate, of which 209 women (71.3%) responded. Thirty-five percent
      of women were overweight and 18% were obese, whilst only 21% met recommendations
      for PA. Obesity was associated with significantly poorer global QoL, physical,
      cognitive and social functioning, a poorer body image and more symptomatology.
      Sedentary behaviour was associated with poorer QoL scores including global QoL,
      physical, role, social and sexual functioning. After adjustment, BMI and PA both
      remained independently associated with QoL scores. CONCLUSION: Obesity and
      inactivity are associated with poorer QoL among ovarian cancer survivors. Future
      interventions promoting PA and weight loss should be evaluated as possible means
      to improve the QoL of this population.

PMID- 26291651
TI  - An Ideal Detector Composed of Two-Dimensional Cd(II)-Triazole Frameworks for
      Nitro-Compound Explosives and Potassium Dichromate.
AB  - The two-dimensional (2D) metal-organic framework (MOF)
      [Cd(TPTZ)(H2O)2(HCOOH)(IPA)2]n (1; TPTZ = {4-[4-(1H-1,2,4-triazol-1
      yl)phenyl]phenyl}-1H-1,2,4-triazole, IPA = isophthalic acid) has been constructed
      with the pi-electron-rich aromatic ligand TPTZ, auxiliary ligand IPA, and the
      metal Cd(2+) ion with a d(10) configuration under solvothermal conditions.
      Complex 1 exhibits a strong ligand-originated photoluminescence emission, which
      is selectively sensitive toward electron-deficient nitroaromatic compounds, such
      as nitrobenzene (NB), 1,3-dinitrobenzene (m-DNB), and 1,4-dinitrobenzene (p-DNB),
      and nitro-aliphatic compounds, such as nitromethane (NM) and
      tris(hydroxymethyl)nitromethane. This property makes complex 1 a potential
      fluorescence sensor for these chemicals. Single-crystal X-ray diffraction studies
      revealed that dinuclear cadmium building units were further bridged by TPTZ
      ligands to give a four-connected uninodal net with the Schlafli symbol of
      [4.6(3).4.6(3).6(2).6(4)].

PMID- 26291652
TI  - Changes in Lateral Comitance After Asymmetric Horizontal Strabismus Surgery.
AB  - IMPORTANCE: Asymmetric horizontal strabismus surgery is often performed to
      correct primary gaze alignment without considering the symptoms that may result
      from misalignment in the patient's side gaze. Surgical choices influence
      alignment in side gaze and may contribute to functional and social deficits.
      OBJECTIVE: To identify the surgical procedures associated with changes of
      alignment in side gaze to help inform surgical planning for patients with
      horizontal strabismus. DESIGN, SETTING, AND PARTICIPANTS: The medical records of
      1081 horizontal strabismus surgical procedures that were performed at Boston
      Children's Hospital during a 2-year period were retrospectively reviewed. Only
      records with strabismus measurements recorded in the right and left gaze before
      and after surgery were included. Data analysis was conducted from September 1,
      2012, through June 7, 2015. MAIN OUTCOMES AND MEASURES: Change in comitance
      (CIC), determined by measuring the horizontal comitance (the difference between
      right- and left-gaze strabismus measurements) before and after surgery. RESULTS:
      The review identified 569 patients who met the inclusion criteria. Of the 491
      patients with comitant preoperative alignment, 59 developed postoperative
      incomitance, of whom 53 (89.9%) had asymmetric surgery. Of the 78 patients with
      incomitant preoperative alignment, 36 patients' (46.2%) deviation had improved to
      comitance after surgery; 32 (88.9%) of these patients had asymmetric surgery.
      Asymmetric 2-muscle surgery had a median CIC of 4.0 while symmetric 2-muscle
      surgery had a median CIC of 1.5 (difference in CIC, 2.5; 95% CI, 2.0-3.0; P <
      .001). A CIC of 25 prism diopters or more was observed in 6 patients who
      underwent asymmetric surgery (0 with symmetric surgery). New postoperative
      incomitance was symptomatic in at least 17 patients (28.8%). CONCLUSIONS AND
      RELEVANCE: Asymmetric strabismus surgery can treat incomitant deviations, but it
      can also create symptomatic incomitant deviations in patients who were previously
      comitant. Surgical planning should include consideration of the potential for
      CIC, including the potential for unsatisfactory appearance in side gaze. Patients
      with binocular vision will be sensitive to diplopia in any gaze direction; in
      such cases, the consequences of asymmetric surgery should be considered with
      particular care.

PMID- 26291653
TI  - A novel in vivo corneal trans-epithelial electrical resistance measurement
      device.
AB  - PURPOSE: To develop a device that is capable of easily measuring corneal
      transepithelial electrical resistance (TER) and changes in the corneal barrier
      function. METHODS: We had previously developed an in vivo method for measuring
      corneal TER using intraocular electrode. This method can be used to precisely
      measure the decline of the corneal barrier function after instillation of
      benzalkonium chloride (BAC). In order to lessen the invasiveness of that
      procedure, we further refined the method for measuring the corneal TER by
      developing electrodes that could be placed on the cornea and in the conjunctival
      sac instead of inserting them into the anterior chamber. TER was then calculated
      by subtracting the electrical resistance, which lacked the corneal epithelial
      input, from the whole electrical resistance that was measured between the
      electrodes. Slit lamp examination and scanning electron microscopy (SEM) were
      used to determine safety of the new device. Corneal TER changes after exposure to
      0.02% BAC were determined using the new device as well as SEM and transmission
      electron microscopy (TEM). RESULTS: Slit lamp examination before and after
      exposure of rabbits' corneas to the sensor confirmed safety of the device. SEM
      examination revealed no difference of the corneal epithelium which exposed to the
      new device with normal corneas. SEM and TEM pictures revealed damaged microvilli
      and tight junctions after instillation of 0.02% BAC. TER change after treatment
      with 0.02%BAC was similar to those determined by the established anterior chamber
      method. CONCLUSION: We succeeded to develop a less invasive device for corneal
      TER measurement in vivo in animals. This new device may be applicable in the
      future for clinical use in humans.

PMID- 26291654
TI  - Two classes of short interfering RNA in RNA silencing.

PMID- 26291655
TI  - The Inhibitory Activity of Plants from Central Argentina on p
      Hydroxyphenylpyruvate Dioxygenase. Isolation and Mechanism of Inhibition of a
      Flavanone from Flourensia oolepis.
AB  - The enzyme 4-hydroxyphenylpyruvate dioxygenase catalyzes the second step in the
      tyrosine degradation pathway. In mammals, this enzyme is the molecular target of
      drugs used for the treatment of metabolic disorders associated with defects in
      the tyrosine catabolism, mainly the fatal hereditary disease tyrosinemia type 1.
      This study evaluated the inhibitory effect of 91 extracts on 4
      hydroxyphenylpyruvate dioxygenase from mostly native plants from central
      Argentina. Flourensia oolepis ethanol extract showed itself to be the most
      effective, and bioguided fractionation yielded pinocembrin (1) as its active
      principle. This flavanone, with an IC50 value of 73.1 uM and a KI of 13.7 uM,
      behaved as a reversible inhibitor of the enzyme and as a noncompetitive
      inhibitor. Molecular modeling studies confirmed the inhibitory potency of 1 and
      explained its activity by means of in silico determination of its binding mode in
      comparison to inhibitors of known activity, cocrystallized with 4
      hydroxyphenylpyruvate dioxygenase. The main structural determinants that confer
      its potency are discussed. Analysis of the binding mode of the flavanone 1 with 4
      hydroxyphenylpyruvate dioxygenase revealed the basis of the noncompetitive
      reversible mechanism of inhibition at the molecular level, which seems to be a
      common feature in this ubiquitous family of natural compounds. The resulting
      information may establish the basis for obtaining novel 4-hydroxyphenylpyruvate
      dioxygenase inhibitors for the treatment of tyrosinemia type 1 and other
      disorders associated with tyrosinase catabolism. 

PMID- 26291656
TI  - The Polyphenolic Composition of Cistus incanus Herbal Tea and Its Antibacterial
      and Anti-adherent Activity against Streptococcus mutans.
AB  - The Mediterranean plant Cistus incanus is rich in polyphenols and has shown
      several pharmacological activities, mainly antibacterial effects. Furthermore, in
      situ studies revealed that a C. incanus infusion reduces the initial bacterial
      adhesion in the oral cavity due to the polyphenols, an indication that C. incanus
      might reduce the risk of caries disease. In the present study, the polyphenols
      from four different commercial C. incanus herbal teas were extracted by
      standardized accelerated solvent extraction for in vitro tests and by an infusion
      for in situ tests. Both extracts were characterized qualitatively and
      quantitatively by high-performance liquid chromatography and only the polyphenol
      content differed slightly. By means of diode array detection and mass
      spectrometry, 29 polyphenols, including ellagitannins, flavanols, and
      glycosylated flavonols, were identified. Thereby, only quantitative but no
      qualitative differences between the four samples were detected. Furthermore, the
      in vitro antibacterial activity of the C. incanus accelerated solvent extracts
      against Streptococcus mutans, one of the primary cariogenic bacterial species,
      was examined using a live/dead assay (BacLight(r)). With this approach, C.
      incanus yielded antibacterial properties. Additional in situ experiments
      indicated that rinses with a C. incanus infusion reduced the initial bacterial
      colonization of enamel samples exposed to oral fluids for over eight hours.
      Furthermore, it was shown by transmission electron microscopy that the
      application of a C. incanus infusion modifies the ultrastructure of the acquired
      enamel pellicle, yielding a more electron-dense morphology. It can be assumed
      that the polyphenols are responsible for the observed effects. 

PMID- 26291657
TI  - Urease inhibitory profile of extracts and chemical constituents of Pistacia
      atlantica ssp. cabulica Stocks.
AB  - The current study was designed to evaluate the urease inhibitory profile of
      extract and fractions of Pistacia atlantica ssp. cabulica Stocks followed by
      bioactivity-guided isolated compounds. The crude extract was found significantly
      active with urease inhibitor (95.40% at 0.2 mg/mL) with IC50 values of 32.0 +/-
      0.28 MUg/mL. Upon fractionation, ethyl acetate fraction displayed 100% urease
      inhibition with IC50 values of 19.9 +/- 0.51 MUg/mL at 0.2 mg/mL. However, n
      hexane and chloroform fractions exhibited insignificant urease inhibition.
      Similarly, the isolated compound, transilitin (1) and dihydro luteolin (2)
      demonstrated marked urease attenuation with 95 and 98% respectively, at 0.15
      mg/mL. Both the isolated compounds showed marked potency with IC50 values of 8.54
      +/- 0.54 and 9.58 +/- 2.22 MUg/mL, respectively. In short, both the extract and
      fractions and isolated compounds showed marked urease inhibition and thus a
      useful natural source of urease inhibition. 

PMID- 26291658
TI  - A novel stereo bioactive metabolite isolated from an endophytic fungus induces
      caspase dependent apoptosis and STAT-3 inhibition in human leukemia cells.
AB  - The present study describes the anti-leukemic potential of a novel stereo
      bioactive secondary metabolite, (R)-5-hydroxy-2-methylchroman-4-one (HMC)
      isolated from a novel endophytic fungus source (Cryptosporiopsis sp. H2-1, NFCCI
      2856), associated with Clidemia hirta. HMC inhibited cell proliferation of
      different cancer cell lines with IC50 values in the range of 8-55 ug/ml. The
      cytotoxicity window of HMC was 6-12 times lower in normal cells as compared to
      susceptible leukemic HL-60, MOLT-4 and K-562 cells. It persuades apoptosis
      through both intrinsic and extrinsic pathways in above leukemic cell lines, which
      was evident through Hoechst staining, Annexin-V binding, cell cycle analysis,
      loss of mitochondrial membrane potential (Deltapsim), release of cytochrome c,
      Bax, Bid, over-expression of apical death receptors, activation of caspase-3,-8,
      9 and PARP (poly ADP ribose polymerase) cleavage. HMC induced caspase dependent
      apoptosis and robustly attenuate transcription factor, p-STAT-3 in myeloid and
      lymphoid leukemia cells. The mechanism of HMC arbitrated inhibition of p-STAT-3
      was due to the activation of ubiquitin dependent degradation of p-STAT-3.
      Therefore, our study not only describes the anti-leukemic potential of HMC but
      also provides insights into how endophytes can be useful in discovery and
      development of novel anticancer therapeutics.

PMID- 26291659
TI  - Efficacy of carvedilol in reversing hypertension induced by chronic intermittent
      hypoxia in rats.
AB  - Animal models of chronic intermittent hypoxia (CIH) mimic the hypertension
      observed in patients with obstructive sleep apnoea. Antihypertensive drugs were
      applied to these animal models to address the physiological mechanism but not to
      revert established hypertension. We aimed to investigate the efficacy of
      carvedilol (CVDL), an unselective beta-blocker that exhibits intrinsic anti
      alpha1-adrenergic and antioxidant activities in a rat model of CIH-induced
      hypertension. The variability of CVDL enantiomers in plasma concentrations was
      also evaluated. Wistar rats with indwelling blood pressure telemeters were
      exposed during their sleep period to 5.6 CIH cycles/h, 10.5 h/day, for 60 days.
      CVDL was administered by gavage beginning on Day 36 of the CIH period and was
      continued for 25 days. R-(+)-CVDL and S-(-)-CVDL plasma concentrations were
      monitored by HPLC. CIH significantly increased diastolic and systolic blood
      pressure by 25.7 and 21.6 mm Hg respectively, while no effect was observed on the
      heart rate (HR). CVDL administration at 10, 30 and 50 mg/kg/day promoted a
      significant reduction in HR but did not affect arterial pressure. The S/(R+S)
      ratio of CVDL enantiomers was lower in rats exposed to CIH. The blockade of the
      sympathetic nervous system together with the putative pleiotropic effects of CVDL
      did not alter the CIH-induced hypertension. Although CIH induced pharmacokinetic
      changes in the R/(R+S) ratio, these effects do not appear to be responsible for
      the inability of CVDL to reverse this particular type of hypertension.

PMID- 26291660
TI  - Current and future treatment strategies for iron overload cardiomyopathy.
AB  - Iron overload cardiomyopathy is the major cause of death in transfusion-dependent
      thalassemia (TDT) patients. Growing evidence demonstrates that combined iron
      chelators, or the combination of an iron chelator with antioxidant(s) are
      effective in diminishing myocardial iron deposition and attenuating cardiac
      dysfunction. This review comprehensively summarizes basic and clinical reports on
      the therapeutic efficacy of combined iron chelators, or the combination of an
      iron chelator with antioxidant(s) on the heart. Promising benefits of these
      treatments in preventing cardiac dysfunction due to iron overload could provide
      extensive insight into future therapeutic strategies for better treatment and
      prevention of cardiomyopathy in TDT patients. 

PMID- 26291661
TI  - Why are second-generation H1-antihistamines minimally sedating?
AB  - H1-antihistamines are widely used in treating allergic disorders, e.g.,
      conjunctivitis, urticaria, dermatitis and asthma. The first-generation H1
      antihistamines have a much greater sedative effect than the second-generation H1
      antihistamines. Researchers could not offer a satisfactory explanations until
      late 1990s when studies showed that second-generation H1-antihistamines were
      substrates of P-glycoprotein. P-glycoprotein, expressed in the blood-brain
      barrier, acts as an efflux pump to decrease the concentration of H1
      antihistamines in the brain, which minimizes drug effects on the central nervous
      system and results in less sedation. P-glycoprotein is found in the apical side
      of the epithelium. It consists of transmembrane domains that bind
      substrates/drugs and nucleotide-binding domains that bind and hydrolyze ATP to
      generate energy for the drug efflux. This review mainly discusses interactions
      between P-glycoprotein and commonly used second-generation H1-antihistamines. In
      addition, it describes other possible determining factors of minimal sedating
      properties of second-generation H1-antihistamines. 

PMID- 26291662
TI  - Effect of combination therapy consisting of enalapril, alpha-lipoic acid, and
      menhaden oil on diabetic neuropathy in a high fat/low dose streptozotocin treated
      rat.
AB  - We have previously demonstrated that treating diabetic rats with enalapril, an
      angiotensin converting enzyme (ACE) inhibitor, alpha-lipoic acid, an antioxidant,
      or menhaden oil, a natural source of omega-3 fatty acids can partially improve
      diabetic peripheral neuropathy. In this study we sought to determine the efficacy
      of combining these three treatments on vascular and neural complications in a
      high fat fed low dose streptozotocin treated rat, a model of type 2 diabetes.
      Rats were fed a high fat diet for 8 weeks followed by a 30 mg/kg dose of
      streptozotocin. Eight weeks after the onset of hyperglycemia diabetic rats were
      treated with a combination of enalapril, alpha-lipoic acid and menhaden oil.
      Diabetic rats not receiving treatment were continued on the high fat diet.
      Glucose clearance was impaired in diabetic rats and significantly improved with
      treatment. Diabetes caused steatosis, elevated serum lipid levels, slowing of
      motor and sensory nerve conduction, thermal hypoalgesia, reduction in
      intraepidermal nerve fiber profiles, decrease in cornea sub-basal nerve fiber
      length and corneal sensitivity and impairment in vascular relaxation to
      acetylcholine and calcitonin gene-related peptide in epineurial arterioles of the
      sciatic nerve. Treating diabetic rats with the combination of enalapril, alpha
      lipoic acid and menhaden oil reversed all these deficits to near control levels
      except for motor nerve conduction velocity which was also significantly improved
      compared to diabetic rats but remained significantly decreased compared to
      control rats. These studies suggest that a combination therapeutic approach may
      be most effective for treating vascular and neural complications of type 2
      diabetes.

PMID- 26291664
TI  - Mirth and laughter elicited by electrical stimulation of the human anterior
      cingulate cortex.
AB  - Laughter is a complex motor behavior that, typically, expresses mirth. Despite
      its fundamental role in social life, knowledge about the neural basis of laughter
      is very limited and mostly based on a few electrical stimulation (ES) studies
      carried out in epileptic patients. In these studies laughter was elicited from
      temporal areas where it was accompanied by mirth and from frontal areas plus an
      anterior cingulate case where laughter without mirth was observed. On the basis
      of these findings, it has been proposed a dichotomy between temporal lobe areas
      processing the emotional content of laughter and anterior cingulate cortex (ACC)
      and motor areas responsible of laughter production. The present study is aimed to
      understand the role of ACC in laughter. We report the effects of stimulation of
      10 rostral, pregenual ACC (pACC) patients in which the ES elicited laughter. In
      half of the patients ES elicited a clear burst of laughter with mirth, while in
      the other half mirth was not evident. This large dataset allow us to offer a more
      reliable picture of the functional contribute of this region in laughter, and to
      precisely localize it in the cingulate cortex. We conclude that the pACC is
      involved in both the motor and the affective components of emotions, and
      challenge the validity of a sharp dichotomy between motor and emotional centers
      for laughing. Finally, we suggest a possible anatomical network for the
      production of positive emotional expressions. 

PMID- 26291663
TI  - Neural networks underlying the metacognitive uncertainty response.
AB  - Humans monitor states of uncertainty that can guide decision-making. These
      uncertain states are evident behaviorally when humans decline to make a
      categorization response. Such behavioral uncertainty responses (URs) have also
      defined the search for metacognition in animals. While a plethora of neuroimaging
      studies have focused on uncertainty, the brain systems supporting a volitional
      strategy shift under uncertainty have not been distinguished from those observed
      in making introspective post-hoc reports of categorization uncertainty. Using
      rapid event-related fMRI, we demonstrate that the neural activity patterns
      elicited by humans' URs are qualitatively different from those recruited by
      associative processes during categorization. Participants performed a one
      dimensional perceptual-categorization task in which an uncertainty-response
      option let them decline to make a categorization response. Uncertainty responding
      activated a distributed network including prefrontal cortex (PFC), anterior and
      posterior cingulate cortex (ACC, PCC), anterior insula, and posterior parietal
      areas; importantly, these regions were distinct from those whose activity was
      modulated by task difficulty. Generally, our results can be characterized as a
      large-scale cognitive control network including recently evolved brain regions
      such as the anterior dorsolateral and medial PFC. A metacognitive theory would
      view the UR as a deliberate behavioral adjustment rather than just a learned
      middle category response, and predicts this pattern of results. These
      neuroimaging results bolster previous behavioral findings, which suggested that
      different cognitive processes underlie responses due to associative learning
      versus the declaration of uncertainty. We conclude that the UR represents an
      elemental behavioral index of metacognition. 

PMID- 26291666
TI  - Is Making a Prognosis for Patients With Drug-induced Liver Injury Putting the
      Cart Before the Horse?

PMID- 26291667
TI  - Trends in the Burden of Nonalcoholic Fatty Liver Disease in a United States
      Cohort of Veterans.
AB  - BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is the leading cause
      of chronic liver disease in the United States. However, few data are available on
      recent trends in the incidence and prevalence of NAFLD in the U.S. METHODS: We
      analyzed the national Veterans Administration databases from 2003 to 2011 and
      calculated the age-adjusted prevalence and incidence of NAFLD for the overall
      sample of patients and by demographic subgroups. We used a previously validated
      algorithm to define NAFLD, which was based on persistent increases in levels of
      liver enzymes in the absence of positive results from tests for hepatitis C or
      hepatitis B or evidence of excessive alcohol use. RESULTS: Of the 9,784,541
      patients with at least 1 visit to the Veterans Administration between 2003 and
      2011, 1,330,600 patients (13.6%) had NAFLD. The annual incidence rates of NAFLD
      remained stable (from 2.2% to 3.2%) during the study duration. The prevalence of
      NAFLD increased from 6.3% in 2003 (95% confidence interval, 6.26%-6.3%) to 17.6%
      in 2011 (95% confidence interval, 17.58%-17.65%), a 2.8-fold increase. The
      incidence and prevalence increased at significantly greater rates in patients
      younger than 45 years vs older patients. CONCLUSIONS: In a U.S. population, the
      annual incidence of NAFLD ranges from 2% to 3%. The prevalence of NAFLD more than
      doubled from 2003 through 2011; it is likely to continue to increase because of a
      steady overall incidence coupled with a rising incidence in younger individuals.

PMID- 26291665
TI  - Current and Future Burden of Chronic Nonmalignant Liver Disease.
AB  - Disease burden is an important indicator of the state of health of a population.
      It can be measured as the frequency (eg, incidence and prevalence) of a condition
      or its effects including fatal and non-fatal health loss from disease (eg,
      disability-adjusted life years) as well as the financial costs (eg, direct
      healthcare costs and indirect healthcare expenditures related to lost income
      because of premature death). Accurate disease burden information is essential for
      policy-making such as prioritization of health interventions and allocation of
      resources. Chronic liver disease (CLD) causes substantial health and economic
      burden in the United States, where nearly 2 million deaths annually are
      attributable to CLD. In the recent past, overall mortality rate of CLD has been
      increasing. Viral hepatitis and alcoholic liver disease are thought to be the
      most common etiologies of chronic liver diseases. More recently, the prevalence
      of nonalcoholic fatty liver disease is rapidly increasing, and nonalcoholic
      steatohepatitis has become a leading indication for liver transplantation. In
      this article, we assemble available data on the burden of CLD in the United
      States, focusing on nonmalignant complications, whereas the impact on mortality
      and healthcare expenses of hepatocellular carcinoma, an important consequence of
      CLD, is discussed elsewhere. 

PMID- 26291668
TI  - An Unusual Skin Manifestation in a Patient With Ulcerative Colitis.

PMID- 26291669
TI  - Unsaturated acyl chains dramatically enhanced cellular uptake by direct
      translocation of a minimalist oligo-arginine lipopeptide.
AB  - The recurring issue with cell penetrating peptides is how to increase direct
      translocation vs. endocytosis, to avoid premature degradation. Acylation by a cis
      unsaturated chain (C22:6) of a short cationic peptide provides a new rational
      design to favour diffuse cytosolic and dense Golgi localisations. 

PMID- 26291670
TI  - JIP4 is a PLK1 binding protein that regulates p38MAPK activity in G2 phase.
AB  - Cell cycle progression from G2 phase into mitosis is regulated by a complex
      network of mechanisms, all of which finally control the timing of Cyclin B/CDK1
      activation. PLK1 regulates a network of events that contribute to regulating G2/M
      phase progression. Here we have used a proteomics approach to identify proteins
      that specifically bind to the Polobox domain of PLK1. This identified a panel of
      proteins that were either associated with PLK1 in G2 phase and/or mitosis, the
      strongest interaction being with the MAPK scaffold protein JIP4. PLK1 binding to
      JIP4 was found in G2 phase and mitosis, and PLK1 binding was self-primed by PLK1
      phosphorylation of JIP4. PLK1 binding is required for JIP4-dependent p38MAPK
      activation in G2 phase during normal cell cycle progression, but not in either G2
      phase or mitotic stress response. Finally, JIP4 is a target for caspase-dependent
      cleavage in mitotically arrested cells. The role for the PLK1-JIP4 regulated
      p38MAPK activation in G2 phase is unclear, but it does not affect either
      progression into or through mitosis. 

PMID- 26291671
TI  - Application of FTIR spectroscopy to the characterization of archeological wood.
AB  - Two archeological wood samples were studied by attenuated total reflectance
      Fourier transform infrared (FTIR-ATR) spectroscopy. They originate from a
      shipwreck in Ribadeo Bay in the northwest of Spain and from a beam wood of an old
      nave of the Cathedral of Segovia in the central Spain. Principal component
      analysis was applied to the transposed data matrix (samples as columns and
      spectral bands as rows) of 43 recorded spectra (18 in the shipwreck and 25 in the
      beam wood). The results showed differences between the two samples, with a larger
      proportion of carbohydrates and smaller proportion of lignin in the beam than in
      the shipwreck wood. Within the beam wood, lignin content was significantly lower
      in the recent than the old tree rings (P=0.005). These variations can be
      attributed to species differences between the two woods (oak and pine
      respectively), with a mixture of guaiacyl and syringyl in hardwood lignin,
      whereas softwood lignin consists almost exclusively of guaiacyl moieties. The
      influence of environmental conditions on the FTIR fingerprint was probably
      reflected by enhanced oxidation of lignin in aerated conditions (beam wood) and
      hydrolysis of carbohydrates in submerged-anoxic conditions (shipwreck wood).
      Molecular characterization by analytical pyrolysis of selected samples from each
      wood type confirmed the interpretation of the mechanisms behind the variability
      in wood composition obtained by the FTIR-ATR. 

PMID- 26291672
TI  - Electrochemical and spectroelectrochemical properties of thiadiazole substituted
      metallo-phthalocyanines.
AB  - 4-Thiadiazole substituted phthalonitrile and peripherally tetra-substituted
      phthalocyanine Cu(II), Fe(II) and Ti(IV)O complexes have been synthesized for the
      first time. Electrochemical properties of these complexes were determined with
      voltammetric and in situ spectroelectrochemical measurements. CuPc has redox
      inactive Cu(2+) center, therefore it gave three Pc based reduction and two Pc
      based oxidation processes. TiOPc and FePc complexes gave metal based redox
      processes in addition to Pc based redox reactions due to the redox activity of
      Ti(4+)O and Fe(2+) metal centers. Although FePc also gave three reduction and two
      oxidation reactions, peak potentials of these processes are different than those
      of CuPc due to the different assignments of the redox reactions. TiOPc went to
      five reduction and one oxidation reactions. Assignments of the redox processes
      were carried out with in situ spectroelectrochemical measurements. Spectra and
      color of the electrogenerated redox species of the complexes were also determined
      with in situ spectroelectrochemical and in situ electrocolorimetric measurements.
      Distinct color differences between the electrogenerated redox species were
      observed, which indicated their possible electrochromic usages. 

PMID- 26291673
TI  - Breast Cancer Mortality After a Diagnosis of Ductal Carcinoma In Situ.
AB  - IMPORTANCE: Women with ductal carcinoma in situ (DCIS), or stage 0 breast cancer,
      often experience a second primary breast cancer (DCIS or invasive), and some
      ultimately die of breast cancer. OBJECTIVE: To estimate the 10- and 20-year
      mortality from breast cancer following a diagnosis of DCIS and to establish
      whether the mortality rate is influenced by age at diagnosis, ethnicity, and
      initial treatment received. DESIGN, SETTING, AND PARTICIPANTS: Observational
      study of women who received a diagnosis of DCIS from 1988 to 2011 in the
      Surveillance, Epidemiology, and End Results (SEER) 18 registries database. Age at
      diagnosis, race/ethnicity, pathologic features, date of second primary breast
      cancer, cause of death, and survival were abstracted for 108,196 women. Their
      risk of dying of breast cancer was compared with that of women in the general
      population. Cox proportional hazards analysis was performed to estimate the
      hazard ratio (HR) for death from DCIS by age at diagnosis, clinical features,
      ethnicity, and treatment. MAIN OUTCOMES AND MEASURES: Ten- and 20-year breast
      cancer-specific mortality. RESULTS: Among the 108 196 women with DCIS, the mean
      (range) age at diagnosis of DCIS was 53.8 (15-69) years and the mean (range)
      duration of follow-up was 7.5 (0-23.9) years. At 20 years, the breast cancer
      specific mortality was 3.3% (95% CI, 3.0%-3.6%) overall and was higher for women
      who received a diagnosis before age 35 years compared with older women (7.8% vs
      3.2%; HR, 2.58 [95% CI, 1.85-3.60]; P < .001) and for blacks compared with non
      Hispanic whites (7.0% vs 3.0%; HR, 2.55 [95% CI, 2.17-3.01]; P < .001). The risk
      of dying of breast cancer increased after experience of an ipsilateral invasive
      breast cancer (HR, 18.1 [95% CI, 14.0-23.6]; P < .001). A total of 517 patients
      died of breast cancer following a DCIS diagnosis (mean follow-up, 7.5 [range, 0
      23.9] years) without experiencing an in-breast invasive cancer prior to death.
      Among patients who received lumpectomy, radiotherapy was associated with a
      reduction in the risk of ipsilateral invasive recurrence at 10 years (2.5% vs
      4.9%; adjusted HR, 0.47 [95% CI, 0.42-0.53]; P < .001) but not of breast cancer
      specific mortality at 10 years (0.8% vs 0.9%; HR, 0.86 [95% CI, 0.67-1.10]; P =
      .22). CONCLUSIONS AND RELEVANCE: Important risk factors for death from breast
      cancer following a DCIS diagnosis include age at diagnosis and black ethnicity.
      The risk of death increases after a diagnosis of an ipsilateral second primary
      invasive breast cancer, but prevention of these recurrences by radiotherapy does
      not diminish breast cancer mortality at 10 years.

PMID- 26291674
TI  - Strain-rate-dependent non-linear tensile properties of the superficial zone of
      articular cartilage.
AB  - AIM OF THE STUDY: The tensile properties of articular cartilage play an important
      role in the compressive behavior and integrity of the tissue. The stress-strain
      relationship of cartilage in compression was observed previously to depend on the
      strain-rate. This strain-rate dependence has been thought to originate mainly
      from fluid pressurization. However, it was not clear to what extent the tensile
      properties of cartilage contribute to the strain-rate dependence in compressive
      behavior of cartilage. The aim of the present study was to quantify the strain
      rate dependent stress-strain relationship and hysteresis of articular cartilage
      in tension. METHODS: Uniaxial tensile tests were performed to examine the strain
      rate dependent non-linear tensile properties of the superficial zone of bovine
      knee cartilage. Tensile specimens were oriented in the fiber direction indicated
      by the India ink method. Seven strain-rates were used in the measurement ranging
      from 0.1 to 80%/s, which corresponded to nearly static to impact joint loadings.
      RESULTS: The experimental data showed substantial strain-rate and strain
      magnitude dependent load response: for a given strain-magnitude, the tensile
      stress could vary by a factor of 1.95 while the modulus by a factor of 1.58 with
      strain-rate; for a given strain-rate, the modulus at 15% strain could be over
      four times the initial modulus at no strain. The energy loss in cartilage tension
      upon unloading exhibited a complex variation with the strain-rate. CONCLUSION:
      The strain-rate dependence of cartilage in tension observed from the present
      study is relatively weaker than that in compression observed previously, but is
      considerable to contribute to the strain-rate dependent load response in
      compression.

PMID- 26291675
TI  - Functional Immune Reconstitution by Interleukin-2 Adjunctive Therapy for
      HIV/Mycobacterial Co-infection.

PMID- 26291676
TI  - A comparative study on biologically and chemically synthesized silver
      nanoparticles induced Heat Shock Proteins on fresh water fish Oreochromis
      niloticus.
AB  - The wide applicability of silver nanoparticles in medicine and pharmaceutical
      industries leads to its over exploitation and thus contaminating our environment.
      Majority of these nanoscale dimension particles finally accumulates in fresh
      water and marine ecosystem. As the nanoparticles behave entirely different from
      its corresponding bulk material, a better understanding of their environmental
      impacts in aquatic ecosystems is inevitable. The study was focused on a
      comparative stress physiology analysis of chemically synthesized silver
      nanoparticles and biogenic silver nanoparticles. Half maximal inhibitory
      concentration of biologically synthesized and chemically synthesized
      nanoparticles was found out (30MUg/mL and 20MUg/mL respectively). The Heat Shock
      Protein (HSP70) secretion was analysed in the fresh water fish Oreochromis
      niloticus after exposing to different concentrations of biologically and
      chemically synthesized silver nanoparticles along with the silver in its ionic
      form. The intense immune-histochemical staining of fish tissues (muscle, kidney
      and liver) analyzed proportionately reflected the stress created. The colour
      intensity was directly proportional to the stress created or the stress protein
      released. High level of HSP70 expression was observed in all of the fish tissues
      exposed to silver ions and chemically synthesized silver nanoparticles, when
      compared to that of biologically synthesized. The results revealed the
      significance of comparatively safe and less toxic biogenic nanoparticles compared
      to the chemically synthesized.

PMID- 26291677
TI  - Toxicity of cobalt ferrite (CoFe2O4) nanobeads in Chlorella vulgaris:
      interaction, adaptation and oxidative stress.
AB  - The potential toxicity of CoFe2O4 nanobeads (NBs) in Chlorella vulgaris was
      observed up to 72h. Algal cell morphology, membrane integrity and viability were
      severely compromised due to adsorption and aggregation of NBs on algal surfaces,
      release of Fe(3+) and Co(2+) ions and possible mechanical damage by NBs.
      Interactions with NBs and effective decrease in ions released by aggregation and
      exudation of algal cells as a self defense mechanism were observed by Fourier
      transform infrared attenuated total reflectance (FTIR-ATR) and inductively
      coupled plasma mass spectrometry (ICP-MS). The results corroborated CoFe2O4 NBs
      induced ROS triggered oxidative stress, leading to a reduction in catalase
      activity, activation of the mutagenic glutathione s-transferase (mu-GST) and acid
      phosphatase (AP) antioxidant enzymes, and an increase in genetic aberrations,
      metabolic and cellular signal transduction dysfunction. Circular dichroism (CD)
      spectra indicated the weak interactions of NBs with BSA, with slight changes in
      the alpha-helix structure of BSA confirming conformational changes in structure,
      hence the potential for functional interactions with biomolecules. Possible
      interferences of CoFe2O4 NBs with assay techniques and components indicated
      CoFe2O4 NBs at lower concentration do not show any significant interference with
      ROS, catalase, mu-GST and no interference with CD measurements. This study showed
      ROS production is one of the pathways of toxicity initiated by CoFe2O4 NBs and
      illustrates the complex processes that may occur between organisms and NBs in
      natural complex ecosystem.

PMID- 26291678
TI  - Multidisciplinary screening of toxicity induced by silica nanoparticles during
      sea urchin development.
AB  - The aim of this study was to investigate the potential toxicity of Silica
      nanoparticles (SiO2 NPs) in seawater by using the sea urchin Paracentrotus
      lividus as biological model. SiO2 NPs exposure effects were identified on the
      sperm of the sea urchin through a multidisciplinary approach, combining
      developmental biology, ecotoxicology, biochemistry, and microscopy analyses. The
      following responses were measured: (i) percentage of eggs fertilized by exposed
      sperm; (ii) percentage of anomalies and undeveloped embryos and larvae; (iii)
      enzyme activity alterations (acetylcholinesterase, AChE) in the early
      developmental stages, namely gastrula and pluteus. Sperms were exposed to
      seawater containing SiO2 NPs suspensions ranging from 0.0001mg/L to 50mg/L.
      Fertilization ability was not affected at any concentration, whereas a
      significant percentage of anomalies in the offspring were observed and quantified
      by means of EC50 at gastrula stage, including undeveloped and anomalous embryos
      (EC50=0.06mg/L), and at pluteus stage, including skeletal anomalies and delayed
      larvae (EC50=0.27mg/L). Moreover, morphological anomalies were observed in larvae
      at pluteus stage, by immunolocalizing molecules involved in larval development
      and neurotoxicity effects - such as acetylated tubulin and choline
      acetyltransferase (ChAT) - and measuring AChE activity. Exposure of sea urchins
      to SiO2 NPs caused neurotoxic damage and a decrease of AChE expression in a non
      dose-dependent manner. In conclusion, through the multidisciplinary approach used
      in this study SiO2 NPs toxicity in sea urchin offspring could be assessed.
      Therefore, the measured responses are suitable for detecting embryo- and larval-
      toxicity induced by these NPs.

PMID- 26291679
TI  - Benzo-alpha-pyrene induced oxidative stress in Caenorhabditis elegans and the
      potential involvements of microRNA.
AB  - In the present study oxidative stress induced by Benzo-alpha-pyrene (BaP)
      exposure and the potential involvements of microRNA were investigated. The
      Caenorhabditis elegans (C. elegans) was applied as model organism. The C. elegans
      at L1-stage were randomly divided into 4 groups and exposed to 0, 0.2, 2.0, and
      20MUM BaP for 30h. Expressions of SKiNhead-1 (SKN-1), gamma-glutamine cysteine
      synthase heavy chain (GCS-1), and their potential regulatory factors in
      insulin/IGF-1/FOXO signaling pathway and the p38 MAPK pathway were analyzed. The
      expressions of potentially involved microRNAs were investigated as well. Results
      demonstrated that expressions of SKN-1 and GCS-1 were altered significantly
      following BaP exposure (P<0.05). Meanwhile, expressions of multiple related
      factors were changed after BaP treatments. The altered factors include AKT-1, DAF
      16, glutathione synthetase (GSS-1), glutathione S-transferase-24 (GST-24),
      mitogen-activated protein kinase kinase-4 (MKK-4), multidrug resistance
      associated protein-1 (MRP-1), and pyruvate dehydrogenase kinase-2 (PDHK-2)
      (P<0.05). In addition, results showed that exposure to BaP led to altered
      expressions of microRNA. Out of the 28 tested microRNAs, expressions of miR-1,
      miR-355, miR-50, miR-51, miR-58, miR-796, miR-797, and miR-84 were modified.
      Findings of the present study include that BaP exposure caused oxidative stress
      in C. elegans. The expressional response of GCS-1 to BaP exposure might be
      independent of the regulation of SKN-1 in C. elegans. The microRNAs might be
      involved in the regulations of SKN-1 and GCS-1 expression following BaP exposure
      in C. elegans.

PMID- 26291680
TI  - Comparison of estimation methods for creating small area rates of acute
      myocardial infarction among Medicare beneficiaries in California.
AB  - Creating local population health measures from administrative data would be
      useful for health policy and public health monitoring purposes. While a wide
      range of options--from simple spatial smoothers to model-based methods--for
      estimating such rates exists, there are relatively few side-by-side comparisons,
      especially not with real-world data. In this paper, we compare methods for
      creating local estimates of acute myocardial infarction rates from Medicare
      claims data. A Bayesian Monte Carlo Markov Chain estimator that incorporated
      spatial and local random effects performed best, followed by a method-of-moments
      spatial Empirical Bayes estimator. As the former is more complicated and time
      consuming, spatial linear Empirical Bayes methods may represent a good
      alternative for non-specialist investigators.

PMID- 26291681
TI  - A descriptive study of the prevalence of parasites and pathogens in Chinese black
      honeybees.
AB  - The Chinese black honey bee is a distinct honey bee subspecies distributed in the
      Xinjiang, Heilongjiang and Jilin Provinces of China. We conducted a study to
      investigate the genetic origin and the parasite/pathogen profile on Chinese black
      honeybees. The phylogenetic analysis indicated that Chinese black honeybees were
      two distinct groups: one group of bees formed a distinct clade that was most
      similar to Apis mellifera mellifera and the other group was a hybrid of the
      subspecies, Apis mellifera carnica, Apis mellifera anatolica and Apis mellifera
      caucasica. This suggests that the beekeeping practices might have promoted gene
      flow between different subspecies. Screening for pathogens and parasites showed
      that Varroa destructor and viruses were detected at low prevalence in Chinese
      black honeybees, compared with Italian bees. Further, a population of pure
      breeding black honeybees, A. m. mellifera, displayed a high degree of resistance
      to Varroa. No Varroa mites or Deformed wing virus could be detected in any
      examined bee colonies. This finding suggests that a population of pure breeding
      Chinese black honeybees possess some natural resistance to Varroa and indicated
      the need or importance for the conservation of the black honeybees in China. 

PMID- 26291682
TI  - Presenting Symptoms Among Black and White Women with Provoked Vulvodynia.
AB  - BACKGROUND: The prevalence of vulvodynia has been reported to be lower in black
      compared to white and Latina women. Use of different terminology to describe
      vulvar pain symptoms may play a role in lower prevalence. The objectives were to
      compare pain descriptors used by black and white women with provoked vulvodynia
      (PVD) to determine the effect of race on symptom reporting. METHODS: Ninety-two
      women, self-identified as black (n = 55) and white (n = 37) with clinically
      confirmed PVD completed a questionnaire containing demographic information and
      vulvar pain characteristics. Variables that were significant with race retained
      in the logistic regression model were included in multivariate analysis to
      determine the effect of race on reporting of vulvar pain symptoms. RESULTS: Of
      statistical significance, white women more often described their pain as burning
      as compared with black women (84% vs. 22%, p <= 0.0001). White women more
      frequently reported their pain as stinging (51% vs. 29%, p = 0.03) and itching
      (32% vs. 15%, p = 0.04) as well, whereas there was a trend for black women to
      more often describe their pain as aching (67% vs. 49%, p = 0.07). Overall, white
      women were 19 times as likely to report their pain as burning (adjusted odds
      ratio [aOR] 18.51, 99% confidence interval [CI] 4.46-76.86). CONCLUSIONS: These
      data suggest that black women are less likely to self-report their vulvar pain as
      burning, the classic symptom of PVD. Cultural influences and different underlying
      pain mechanisms may contribute to differences in symptom reporting by race.

PMID- 26291683
TI  - Estrogen Upregulates Slug to Enhance the Migration of Keratinocytes.

PMID- 26291684
TI  - Circadian Gene Clock Regulates Psoriasis-Like Skin Inflammation in Mice.
AB  - There are several reports suggesting that the pathophysiology of psoriasis may be
      associated with aberrant circadian rhythms. However, the mechanistic link between
      psoriasis and the circadian time-keeping system, "the circadian clock," remains
      unclear. This study determined whether the core circadian gene, Clock, had a
      regulatory role in the development of psoriasis. For this purpose, we compared
      the development of psoriasis-like skin inflammation induced by the Toll-like
      receptor 7 ligand imiquimod (IMQ) between wild-type mice and mice with a loss-of
      function mutation of Clock. We also compared the development of IMQ-induced
      dermatitis between wild-type mice and mice with a loss-of-function mutation of
      Period2 (Per2), another key circadian gene that inhibits CLOCK activity. We found
      that Clock mutation ameliorated IMQ-induced dermatitis, whereas the Per2 mutation
      exaggerated IMQ-induced dermatitis, when compared with wild-type mice associated
      with decreased or increased IL-23 receptor (IL-23R) expression in gamma/delta+ T
      cells, respectively. In addition, CLOCK directly bound to the promoter of IL-23R
      in gamma/delta+ T cells, and IL-23R expression in the mouse skin was under
      circadian control. These findings suggest that Clock is a novel regulator of
      psoriasis-like skin inflammation in mice via direct modulation of IL-23R
      expression in gamma/delta+ T cells, establishing a mechanistic link between
      psoriasis and the circadian clock.

PMID- 26291685
TI  - The pelvic floor muscle hyperalgesia (PFMH) scoring system: a new classification
      tool to assess women with chronic pelvic pain: multicentre pilot study of
      validity and reliability.
AB  - OBJECTIVE: The contribution of pelvic floor muscle tenderness to chronic pelvic
      pain (CPP) is well established in the literature. However pelvic floor muscle
      hyperalgesia (PFMH) is often missed during vaginal examination of women with CPP.
      To our knowledge criteria for diagnosing PFMH has not been established or
      validated so far. The aim of this study is to assess the validity and reliability
      of the PFMH scoring system. STUDY DESIGN: Women with and without PFMH were
      recruited prospectively. Digital pelvic examination was performed to detect any
      pain. All women were asked to report of any discomfort or pain evoked by digital
      palpation of the PFMs and to rate the severity of pain/discomfort as none (grade
      0), mild (grade I) moderate (grade II) or severe (grade III). All women were also
      asked to describe the severity of the pain/discomfort using a visual analogue
      scale (VAS). Following examination a PFMH score was given according to each
      patient's reactions. Intra-observer and inter-observer reliability was assessed.
      Construct and content validity was also determined. RESULTS: 111 (44 symptomatic
      and 67 controls) were recruited. Intraobserver reliability had ICCs between 0.426
      and 0.804. Interobserver reliability had ICCs between 0.724 and 0.917. There was
      a good correlation between PFMH scores and VAS scores (rho 0.994, p<0.01). Total
      scores between symptomatic and controls were significantly different (p<0.01 Mann
      Whitney U test). CONCLUSION: The PFMH scoring system is a simple, reliable, valid
      and easy screening tool for in the assessment of women with CPP.

PMID- 26291686
TI  - Can we predict urinary stress incontinence by using demographic, clinical,
      imaging and urodynamic data?
AB  - OBJECTIVE: It has been claimed that urethral hypermobility and resting urethral
      pressure can largely explain stress incontinence in women. In this study we tried
      to replicate these findings in an unselected cohort of women seen for urodynamic
      testing, including as many potential confounders as possible. STUDY DESIGN: This
      study is a retrospective analysis of data obtained from 341 women. They attended
      for urodynamic testing due to symptoms of pelvic floor dysfunction. We excluded
      from the analysis women with a history of previous anti-incontinence and prolapse
      surgery. All patients had a standardised clinical assessment, 4D transperineal
      pelvic floor ultrasound and multichannel urodynamic testing. Urodynamic stress
      incontinence (USI) was diagnosed by multichannel urodynamic testing. Its severity
      was subjectively graded as mild, moderate and severe. Candidate variables were:
      age, BMI, symptoms of prolapse, vaginal parity, significant prolapse (compartment
      specific), levator avulsion, levator hiatal area, Oxford grading, midurethral
      mobility, maximum urethral pressure (MUP), maximum cough pressure and maximum
      Valsalva pressure reached. RESULTS: On binary logistic regression, the following
      parameters were statistically significant in predicting urodynamic stress
      incontinence: age (P=0.03), significant rectocele (P=0.02), max. abdominal
      pressure reached (negatively, P<0.0001), midurethral mobility (P=0.0004) and MUP
      (negatively, P<0.0001). On multivariate analysis, accounting for multiple
      interdependencies, the following predictors remained significant: max. abdominal
      pressure reached (negatively, P<0.0001), cough pressure (P=0.006), midurethral
      mobility (P=0.003) and MUP (negatively, P<0.0001), giving an R(2) of 0.24.
      CONCLUSIONS: Mid-urethral mobility and MUP are the main predictors of USI.
      Demographic and clinical data are at best weak predictors. Our results suggest
      the presence of major unrecognised confounders.

PMID- 26291687
TI  - Ageing effects on the diameter, nanomechanical properties and tactile perception
      of human hair.
AB  - BACKGROUND: The typical changes to hair associated with ageing are greying,
      thinning, dryness and brittleness. Research on the influence of ageing on hair
      properties will enable a detailed understanding of the natural ageing process.
      METHODS: The studies were carried out using an SEM (scanning electron
      microscope), a TriboIndenter and an artificial finger. Three characteristic
      features of tactile perception that could reflect the perceptual dimensions of
      the fineness, roughness and slipperiness of hair were extracted. The influences
      of ageing on the diameter, surface topography, nanomechanical properties and
      tactile perception of hair were determined. RESULTS: In the three age group hair
      samples, the children's group hair samples have the smallest diameter. The hair
      cuticles in the children and young adult groups were relatively complete and less
      damaged than in the elderly group. The hardness and elastic modulus of the young
      adult group's hair samples were higher than those in the elderly and children's
      groups. For all groups, loss modulus E" was smaller than storage modulus E'.
      Vertical deviations (R) and coefficient of friction (MU) increased, and spectral
      centroid (SC) decreased, with the increase in age. Ageing decreased the tactile
      perception of hair. CONCLUSION: Ageing influences the diameter, surface
      topography, hardness, loss modulus, storage modulus and tactile perception of
      human hair.

PMID- 26291688
TI  - Latent inhibition of conditioned taste aversion in rats with excitotoxic dorsal
      hippocampal lesions.
AB  - The hippocampus plays crucial roles for the acquisition of latent inhibition in
      different associative learning procedures, such as fear conditioning. However,
      the involvement of the hippocampus in the latent inhibition of conditioned taste
      aversion (CTA) is uncertain. Because different subregions of the hippocampus are
      associated with distinct functions, it is possible that specific regions of this
      structure are selectively involved in this learning. To explore the relationship
      between the dorsal hippocampal region and the latent inhibition of CTA, we
      analyzed the behavioral effects of excitotoxic lesions of the dorsal hippocampus
      vs. sham lesions in this paradigm. The results provide no evidence that the
      latent inhibition of CTA is compromised in rats with excitotoxic dorsal
      hippocampal lesions. The differential involvement of specific hippocampal regions
      in the latent inhibition of other associative learning paradigms is briefly
      discussed.

PMID- 26291690
TI  - Molecular knots in biology and chemistry.
AB  - Knots and entanglements are ubiquitous. Beyond their aesthetic appeal, these
      fascinating topological entities can be either useful or cumbersome. In recent
      decades, the importance and prevalence of molecular knots have been increasingly
      recognised by scientists from different disciplines. In this review, we provide
      an overview on the various molecular knots found in naturally occurring
      biological systems (DNA, RNA and proteins), and those created by synthetic
      chemists. We discuss the current knowledge in these fields, including recent
      developments in experimental and, in some cases, computational studies which are
      beginning to shed light into the complex interplay between the structure,
      formation and properties of these topologically intricate molecules. 

PMID- 26291689
TI  - Connectivity-based whole brain dual parcellation by group ICA reveals tract
      structures and decreased connectivity in schizophrenia.
AB  - Mapping brain connectivity based on neuroimaging data is a promising new tool for
      understanding brain structure and function. In this methods paper, we demonstrate
      that group independent component analysis (GICA) can be used to perform a dual
      parcellation of the brain based on its connectivity matrix (cmICA). This dual
      parcellation consists of a set of spatially independent source maps, and a
      corresponding set of paired dual maps that define the connectivity of each source
      map to the brain. These dual maps are called the connectivity profiles of the
      source maps. Traditional analysis of connectivity matrices has been used
      previously for brain parcellation, but the present method provides additional
      information on the connectivity of these segmented regions. In this paper, the
      whole brain structural connectivity matrices were calculated on a 5 mm(3) voxel
      scale from diffusion imaging data based on the probabilistic tractography method.
      The effect of the choice of the number of components (30 and 100) and their
      stability were examined. This method generated a set of spatially independent
      components that are consistent with the canonical brain tracts provided by
      previous anatomic descriptions, with the high order model yielding finer
      segmentations. The corpus-callosum example shows how this method leads to a
      robust parcellation of a brain structure based on its connectivity properties. We
      applied cmICA to study structural connectivity differences between a group of
      schizophrenia subjects and healthy controls. The connectivity profiles at both
      model orders showed similar regions with reduced connectivity in schizophrenia
      patients. These regions included forceps major, right inferior fronto-occipital
      fasciculus, uncinate fasciculus, thalamic radiation, and corticospinal tract.
      This paper provides a novel unsupervised data-driven framework that summarizes
      the information in a large global connectivity matrix and tests for brain
      connectivity differences. It has the potential for capturing important brain
      changes related to disease in connectivity-based disorders.

PMID- 26291692
TI  - Successful Unrelated Stem Cell Transplantation in an Infant With Congenital Acute
      Myelogenous Leukemia FAB M5 Showing Massive Cutaneous Infiltrations--A
      Challenging Multidisciplinary Approach.
AB  - The multidisciplinary management of a male neonate presenting with congenital
      acute myelogenous leukemia of monoblastic phenotype is reported using
      conventional chemotherapy, high dose conditioning, and matched unrelated donor
      stem cell transplantation. These therapies were combined to add a graft versus
      leukemia effect to the treatment. Although chimerism studies showed a decrease of
      donor white blood cells, T-cells remained stable of allogeneic origin. We
      hypothesize that a continuous graft versus leukemia effect results in minimal
      residual disease negativity for now more than 18 months since stem cell
      transplantation.

PMID- 26291693
TI  - Adherence to controller asthma medications: 6-month prevalence across a US
      community pharmacy chain.
AB  - WHAT IS KNOWN AND OBJECTIVE: Non-adherence to controller asthma medications is an
      important public health problem. It is estimated to occur in 30-70% of
      individuals and is a significant risk factor for asthma morbidity and mortality.
      The aim of this study was to determine the level of adherence, as indicated by
      refill rates, to controller asthma medications in a community pharmacy setting.
      METHODS: Secondary analyses of a community pharmacy dispensing database in 15
      locations throughout Utah. RESULTS AND DISCUSSION: The dispensing records of 2193
      patients who received controller medications for asthma in a 12-month period, and
      had a minimum of 6-month potential coverage (180 days) from the date of their
      first receipt of a controller medication in that period, were examined. Using
      standard metrics to gauge adherence, the proportion of days covered (PDC) and the
      medication possession ratio (MPR), the average coverage for controller asthma
      medications across a 6-month period (180 days) was poor, averaging less than 50%
      of days' availability. Standard cut-offs (>=80% medication availability)
      indicated that only 14-16% of patients had 'satisfactory' adherence over their 6
      month follow-on period. Females and older patients had significantly greater
      satisfactory adherence. Medication adherence was significantly greater with
      inhaled corticosteroid (ICS)-long-acting beta2 -agonist (LABA) combinations than
      with ICS alone. WHAT IS NEW AND CONCLUSION: This study confirms the considerable
      scope of the asthma therapy non-adherence problem. Therefore, it is imperative to
      conduct survey-based research linked directly to pharmacy-based dispensing data
      to derive patient behavioural, attitudinal and environmental factors that may
      contribute to the issue, and then pilot and evaluate interventions for change.

PMID- 26291694
TI  - Lack of concordance in parapneumonic effusion management in children in central
      Europe.
AB  - Treatment of parapneumonic effusion in children remains controversial in the
      literature and in clinical practice. The aim of this study was to determine
      whether mutual consensus exists in the diagnosis and treatment of parapneumonic
      effusion in Central European countries. A questionnaire was sent to all directors
      of pediatric respiratory units in four adjacent Central European countries
      (Austria, France, Germany, Switzerland). The response rate was 61.8%. Responses
      reflected acceptable agreement regarding initial diagnostic procedures, as most
      centers performed chest X-ray and biological exams, followed by ultrasound,
      thoracocentesis, or computed tomography. However, antibiotic regimens were very
      heterogeneous, and the survey revealed complete lack of agreement on the
      indications and effusion volume threshold for invasive procedures, such as
      fibrinolytic instillation and thoracoscopy. In conclusion, apart from initial
      diagnostic procedures, this study showed a lack of mutual consensus among the
      four countries regarding the management of pediatric parapneumonic effusion.
      Multicenter prospective trials are clearly needed to acquire more evidence on the
      management of childhood parapneumonic effusion, enabling the development of
      evidence-based algorithms that could help to avoid unnecessary examinations with
      potential long-term side effects, such as radiation exposure at a young age.

PMID- 26291691
TI  - Adipose tissue and metabolic syndrome: too much, too little or neither.
AB  - Obesity is strongly associated with metabolic syndrome. Recent research suggests
      that excess adipose tissue plays an important role in development of the
      syndrome. On the other hand, persons with a deficiency of adipose tissue (e.g.
      lipodystrophy) also manifest the metabolic syndrome. In some animal models,
      expansion of adipose tissue pools mitigates adverse metabolic components (e.g.
      insulin resistance, hyperglycaemia and dyslipidemia). Hence, there are
      conflicting data as to whether adipose tissue worsens the metabolic syndrome or
      protects against it. This conflict may relate partly to locations of adipose
      tissue pools. For instance, lower body adipose tissue may be protective whereas
      upper body adipose tissue may promote the syndrome. One view holds that in either
      case, the accumulation of ectopic fat in muscle and liver is the driving factor
      underlying the syndrome. If so, there may be some link between adipose tissue fat
      and ectopic fat. But the mechanisms underlying this connection are not clear. A
      stronger association appears to exist between excessive caloric intake and
      ectopic fat accumulation. Adipose tissue may act as a buffer to reduce the impact
      of excess energy consumption by fat storage; but once a constant weight has been
      achieved, it is unclear whether adipose tissue influences levels of ectopic fat.
      Another mechanism whereby adipose tissue could worsen the metabolic syndrome is
      through release of adipokines. This is an intriguing mechanism, but the impact of
      adipokines on metabolic syndrome risk factors is uncertain. Thus, many potential
      connections between adipose tissue and metabolic syndrome remain to unravelled. 

PMID- 26291695
TI  - Functional dysconnection in the prefrontal-amygdala circuitry in unaffected
      siblings of patients with bipolar I disorder.
AB  - OBJECTIVES: Bipolar I disorder (BD) is a highly heritable disorder characterized
      by mood swings between high-energy and low-energy states. Amygdala hyperactivity
      and cortical inhibitory hypoactivity [e.g., of the dorsolateral prefrontal cortex
      (dlPFC)] have been found in patients with BD, as evidenced by their abnormal
      resting-state functional connectivity (FC) and glucose utilization (GU). However,
      it has not been determined whether functional abnormalities of the dlPFC-amygdala
      circuit exist in unaffected, healthy siblings of the patients with BD (BDsib).
      METHODS: Twenty euthymic patients with BD, 20 unaffected matching BDsib of the
      patient group, and 20 well-matched healthy control subjects were recruited. We
      investigated seed-based FC (seeds: dlPFC) with resting-state functional magnetic
      resonance imaging and GU in the regions of interest (e.g., dlPFC and amygdala)
      using (18) F-fluorodeoxyglucose positron emission tomography. RESULTS: The FC in
      the dlPFC (right)-amygdala circuit was statistically abnormal in patients with BD
      and BDsib, but only the patients with BD demonstrated hypoactive GU bilaterally
      in the dlPFC and hyperactive GU bilaterally in the amygdala. Facilitating
      differentiation between the BD groups, the altered FC between dlPFC (right) and
      amygdala (left) was even more prominent in the patients with BD (p < 0.05).
      CONCLUSIONS: There was a dysfunctional connection with intact GU in the dlPFC
      amygdala circuit of the BDsib, which highlights the vulnerability in families
      with BD. Diminished top-down control from the bilateral dlPFC, which prevents
      adequate inhibition of limbic hyperactivity, might mediate the development of BD.

PMID- 26291698
TI  - Olmesartan-associated enteropathy: new insights on the natural history? Report of
      two cases.
AB  - INTRODUCTION: The association between olmesartan and an enteropathy
      histologically indistinguishable from untreated celiac disease has recently been
      described. However, pathogenetic mechanisms leading to villous atrophy,
      prevalence, natural history and genetic background of this condition have not yet
      been defined. PATIENTS: We describe here two cases of olmesartan-associated
      enteropathy and discuss some aspects of the natural history of this condition.
      RESULTS: In both patients, an infectious episode seems to have triggered the
      severe malabsorption syndrome which led them to hospitalization. High titer
      positive antinuclear antibodies with homogeneous pattern were found. CONCLUSIONS:
      Our reports add to a growing body of evidence suggesting that olmesartan
      associated enteropathy should be considered in the presence of villous atrophy
      and negative celiac serology and in the diagnostic algorithm of non-responsive
      celiac disease.

PMID- 26291699
TI  - Concomitant colonic disease (Montreal L3) and re-resectional surgery are
      predictors of clinical recurrence following ileocolonic resection for Crohn's
      disease.
AB  - AIM: Ileocolonic resection is reserved for patients with moderate to severe
      Crohn's disease. Postoperative clinical recurrence can occur in up to 55% of
      patients within 5 years. Predicting the risk of recurrence is key in deciding
      upon appropriate treatment strategies. This study aims to determine the incidence
      of postoperative clinical recurrence and predictors of recurrence in a specialist
      institution. METHOD: The clinical case records of 142 patients who underwent
      either a one-stage or two-stage procedure for ileocolonic Crohn's disease from 1
      January 2005 to 31 December 2010 were reviewed. Preoperative, perioperative and
      postoperative variables were extracted. Postoperative clinical recurrence was
      defined as an initiation or change in medical treatment for recurrent symptoms
      with endoscopic or radiological evidence of active disease. Time to clinical
      recurrence was measured in months after surgery. Univariate and multivariate
      analyses were performed. RESULTS: Over the 6-year period, follow-up data were
      obtained on 142 patients over a median of 28.5 months. Clinical recurrence was
      demonstrated in 59 (41.5%) patients. The proportion of patients with clinical
      recurrence at 5 years was 48.2%. Predictors of recurrence included a re-resection
      for recurrent disease [hazard ratio (HR) 1.9; 95% CI 1.1-3.3; P = 0.02] and
      ileocolonic disease (HR 1.7; 95% CI 1.0-2.9; P = 0.05). CONCLUSION: Identifying
      the predictors for postoperative clinical recurrence is important for determining
      the postoperative strategy. This study provides a unique perspective on the
      incidence of recurrence and associated predictors from the perspective of a
      specialist unit.

PMID- 26291697
TI  - Self-Organization of Microcircuits in Networks of Spiking Neurons with Plastic
      Synapses.
AB  - The synaptic connectivity of cortical networks features an overrepresentation of
      certain wiring motifs compared to simple random-network models. This structure is
      shaped, in part, by synaptic plasticity that promotes or suppresses connections
      between neurons depending on their joint spiking activity. Frequently,
      theoretical studies focus on how feedforward inputs drive plasticity to create
      this network structure. We study the complementary scenario of self-organized
      structure in a recurrent network, with spike timing-dependent plasticity driven
      by spontaneous dynamics. We develop a self-consistent theory for the evolution of
      network structure by combining fast spiking covariance with a slow evolution of
      synaptic weights. Through a finite-size expansion of network dynamics we obtain a
      low-dimensional set of nonlinear differential equations for the evolution of two
      synapse connectivity motifs. With this theory in hand, we explore how the form of
      the plasticity rule drives the evolution of microcircuits in cortical networks.
      When potentiation and depression are in approximate balance, synaptic dynamics
      depend on weighted divergent, convergent, and chain motifs. For additive, Hebbian
      STDP these motif interactions create instabilities in synaptic dynamics that
      either promote or suppress the initial network structure. Our work provides a
      consistent theoretical framework for studying how spiking activity in recurrent
      networks interacts with synaptic plasticity to determine network structure. 

PMID- 26291701
TI  - Evidence-Based Abdominal Wall Reconstruction: The Maxi-Mini Approach.
AB  - Complex abdominal wall reconstruction is a high-risk procedure, but it can be
      performed safely if a systematic approach is followed. In this article, the
      authors present their evidence-based technique for abdominal wall reconstruction.
      This approach aims at reducing rates of complications and hernia recurrence,
      starting with critical patient selection; preoperative patient optimization;
      adherence to intraoperative principles including preservation of vascular
      perforators through maintenance of composite tissue with limited undermining;
      direct supported mesh reinforcement of midline musculofascial reapproximation;
      use of percutaneous transfascial suture mesh fixation; careful attention to dead
      space obliteration in any plane; and aggressive soft-tissue resection of
      marginal, undermined, or tenuous skin and subcutaneous tissue. Postoperative
      strategies to decrease complications are also used. The authors' surgical
      technique is described in detail, and pilot data are presented to support the
      authors' approach.

PMID- 26291702
TI  - The Impact of Postoperative Expansion Initiation Timing on Breast Expander
      Capsular Characteristics: A Prospective Combined Clinical and Scanning Electron
      Microscopy Study.

PMID- 26291700
TI  - Chromosome Condensation 1-Like (Chc1L) Is a Novel Tumor Suppressor Involved in
      Development of Histiocyte-Rich Neoplasms.
AB  - Human chromosomal region 13q14 is a deletion hotspot in prostate cancer, multiple
      myeloma, and chronic lymphocytic leukemia. This region is believed to host
      multiple tumor suppressors. Chromosome Condensation 1-like (CHC1L) is located at
      13q14, and found within the smallest common region of loss of heterozygosity in
      prostate cancer. Decreased expression of CHC1L is linked to pathogenesis and
      progression of both prostate cancer and multiple myeloma. However, there is no
      direct evidence for CHC1L's putative tumor suppressing role in current
      literature. Presently, we describe the generation and characterization of Chc1L
      knockout mice. Chc1L-/- mice do not develop cancer at a young age, but bone
      marrow and spleen cells from 8-12 week-old mice display an exaggerated
      proliferative response. By approximately two years of age, knockout and
      heterozygote mice have a markedly increased incidence of tumorigenesis compared
      to wild-type controls, with tumors occurring mainly in the spleen, mesenteric
      lymph nodes, liver and intestinal tract. Histopathological analysis found that
      most heterozygote and knockout mice succumb to either Histiocytic Sarcoma or
      Histiocyte-Associated Lymphoma. Our study suggests that Chc1L is involved in
      suppression of these two histiocyte-rich neoplasms in mice and supports clinical
      data suggesting that CHC1L loss of function is an important step in the
      pathogenesis of cancers containing 13q14 deletion. 

PMID- 26291703
TI  - Midcheek Lift Using Facial Soft-Tissue Spaces of the Midcheek.
AB  - BACKGROUND: This article describes a preperiosteal midcheek lift technique
      performed by means of the midcheek soft-tissue spaces by precise release of the
      retaining ligaments that separate the spaces. METHODS: From November of 2009 to
      June of 2014, 184 patients underwent this procedure. A transcutaneous lower
      eyelid blepharoplasty incision was used to access the preseptal space. Medially,
      the orbicularis oculi origins and tear trough ligament are released sharply,
      connecting the dissection with the premaxillary space. More laterally, the
      orbicularis retaining ligament is released, connecting the dissection with the
      prezygomatic space. With this release, the entire midcheek can be effectively
      lifted. The fat pads were managed by transposition, excision, or with septal
      resets as indicated. Canthopexy is performed routinely to provide lower eyelid
      support. Superolateral traction on the orbicularis oculi elevates the entire
      midcheek, and this was secured to the lateral orbital rim periosteum. In patients
      with significant volume loss in the midcheek, structural fat grafting is
      performed. RESULTS: All patients demonstrated a significant rejuvenation of the
      midcheek with elimination of the eye bags and elevation of the lid-cheek junction
      and the cheek prominence and improvement of the nasolabial folds. The majority of
      the patients (96 percent) were satisfied with the procedure. Complication rates
      were low. Ectropion occurred in 1 percent of patients, and lower lid retraction
      occurred in 1 percent of patients. CONCLUSION: The midcheek lift by means of the
      facial soft-tissue spaces is safe, effective, and long lasting. As the dissection
      is atraumatic, recovery is quick and complications are minimized.

PMID- 26291704
TI  - Face Lift and Lipofilling: Clinical Considerations.

PMID- 26291705
TI  - The Challenges in Presenting Complex Studies.

PMID- 26291706
TI  - Reply: Surgical Treatment and Reconstruction of Nonmelanoma Facial Skin Cancers.

PMID- 26291707
TI  - Reply: Unilateral Cleft Lip Repair Using the Anatomical Subunit Approximation:
      Modifications and Analysis of Early Results in 100 Consecutive Cases.

PMID- 26291708
TI  - Local Flap for Reconstruction of Nonmelanoma Facial Skin Cancer.

PMID- 26291709
TI  - Lycopene Protects against Hypoxia/Reoxygenation Injury by Alleviating ER Stress
      Induced Apoptosis in Neonatal Mouse Cardiomyocytes.
AB  - Endoplasmic reticulum (ER) stress induced apoptosis plays a pivotal role in
      myocardial ischemia/reperfusion (I/R)-injury. Inhibiting ER stress is a major
      therapeutic target/strategy in treating cardiovascular diseases. Our previous
      studies revealed that lycopene exhibits great pharmacological potential in
      protecting against the I/R-injury in vitro and vivo, but whether attenuation of
      ER stress (and) or ER stress-induced apoptosis contributes to the effects remains
      unclear. In the present study, using neonatal mouse cardiomyocytes to establish
      an in vitro model of hypoxia/reoxygenation (H/R) to mimic myocardium I/R in vivo,
      we aimed to explore the hypothesis that lycopene could alleviate the ER stress
      and ER stress-induced apoptosis in H/R-injury. We observed that lycopene
      alleviated the H/R injury as revealed by improving cell viability and reducing
      apoptosis, suppressed reactive oxygen species (ROS) generation and improved the
      phosphorylated AMPK expression, attenuated ER stress as evidenced by decreasing
      the expression of GRP78, ATF6 mRNA, sXbp-1 mRNA, eIF2alpha mRNA and eIF2alpha
      phosphorylation, alleviated ER stress-induced apoptosis as manifested by reducing
      CHOP/GADD153 expression, the ratio of Bax/Bcl-2, caspase-12 and caspase-3
      activity in H/R-treated cardiomyocytes. Thapsigargin (TG) is a potent ER stress
      inducer and used to elicit ER stress of cardiomyocytes. Our results showed that
      lycopene was able to prevent TG-induced ER stress as reflected by attenuating the
      protein expression of GRP78 and CHOP/GADD153 compared to TG group, significantly
      improve TG-caused a loss of cell viability and decrease apoptosis in TG-treated
      cardiomyocytes. These results suggest that the protective effects of lycopene on
      H/R-injury are, at least in part, through alleviating ER stress and ER stress
      induced apoptosis in neonatal mouse cardiomyocytes. 

PMID- 26291710
TI  - RNAi-based therapeutic nanostrategy: IL-8 gene silencing in pancreatic cancer
      cells using gold nanorods delivery vehicles.
AB  - RNA interference (RNAi)-based gene silencing possesses great ability for
      therapeutic intervention in pancreatic cancer. Among various oncogene mutations,
      Interleukin-8 (IL-8) gene mutations are found to be overexpressed in many
      pancreatic cell lines. In this work, we demonstrate IL-8 gene silencing by
      employing an RNAi-based gene therapy approach and this is achieved by using gold
      nanorods (AuNRs) for efficient delivery of IL-8 small interfering RNA (siRNA) to
      the pancreatic cell lines of MiaPaCa-2 and Panc-1. Upon comparing to Panc-1
      cells, we found that the dominant expression of the IL-8 gene in MiaPaCa-2 cells
      resulted in an aggressive behavior towards the processes of cell invasion and
      metastasis. We have hence investigated the suitability of using AuNRs as novel
      non-viral nanocarriers for the efficient uptake and delivery of IL-8 siRNA in
      realizing gene knockdown of both MiaPaCa-2 and Panc-1 cells. Flow cytometry and
      fluorescence imaging techniques have been applied to confirm transfection and
      release of IL-8 siRNA. The ratio of AuNRs and siRNA has been optimized and
      transfection efficiencies as high as 88.40 +/- 2.14% have been achieved. Upon
      successful delivery of IL-8 siRNA into cancer cells, the effects of IL-8 gene
      knockdown are quantified in terms of gene expression, cell invasion, cell
      migration and cell apoptosis assays. Statistical comparative studies for both
      MiaPaCa-2 and Panc-1 cells are presented in this work. IL-8 gene silencing has
      been demonstrated with knockdown efficiencies of 81.02 +/- 10.14% and 75.73 +/-
      6.41% in MiaPaCa-2 and Panc-1 cells, respectively. Our results are then compared
      with a commercial transfection reagent, Oligofectamine, serving as positive
      control. The gene knockdown results illustrate the potential role of AuNRs as non
      viral gene delivery vehicles for RNAi-based targeted cancer therapy applications.

PMID- 26291712
TI  - Disseminated Enteroviral Infection Associated with Obinutuzumab.
AB  - Two cases of disseminated enteroviral infection occurred in patients who received
      the CD20 monoclonal antibody obinutuzumab. Clinical features included hepatitis,
      edema, and a dermatomyositis-like syndrome. These manifestations may be
      unfamiliar to clinicians and are possibly responsive to intravenous
      immunoglobulin. Clinicians should remain vigilant for enteroviral infections in
      patients receiving obinutuzumab. 

PMID- 26291711
TI  - sRNA-Mediated Regulation of P-Fimbriae Phase Variation in Uropathogenic
      Escherichia coli.
AB  - Uropathogenic Escherichia coli (UPEC) are capable of occupying physiologically
      distinct intracellular and extracellular niches within the urinary tract. This
      feat requires the timely regulation of gene expression and small RNAs (sRNAs) are
      known to mediate such rapid adjustments in response to changing environmental
      cues. This study aimed to uncover sRNA-mediated gene regulation in the UPEC
      strain UTI89, during infection of bladder epithelial cells. Hfq is an RNA
      chaperone known to facilitate and stabilize sRNA and target mRNA interactions
      with bacterial cells. The co-immunoprecipitation and high throughput RNA
      sequencing of Hfq bound sRNAs performed in this study, revealed distinct sRNA
      profiles in UPEC in the extracellular and intracellular environments. Our
      findings emphasize the importance of studying regulatory sRNAs in a biologically
      relevant niche. This strategy also led to the discovery of a novel virulence
      associated trans-acting sRNA-PapR. Deletion of papR was found to enhance adhesion
      of UTI89 to both bladder and kidney cell lines in a manner independent of type-1
      fimbriae. We demonstrate PapR mediated posttranscriptional repression of the P
      fimbriae phase regulator gene papI and postulate a role for such regulation in
      fimbrial cross-talk at the population level in UPEC. Our results further
      implicate the Leucine responsive protein (LRP) as a transcriptional activator
      regulating PapR expression. Our study reports, for the first time, a role for
      sRNAs in regulation of P-fimbriae phase variation and emphasizes the importance
      of studying pathogenesis-specific sRNAs within a relevant biological niche. 

PMID- 26291713
TI  - An allolactose trapped at the lacZ beta-galactosidase active site with its
      galactosyl moiety in a (4)H3 conformation provides insights into the formation,
      conformation, and stabilization of the transition state.
AB  - When lactose was incubated with G794A-beta-galactosidase (a variant with a
      "closed" active site loop that binds transition state analogs well) an
      allolactose was trapped with its Gal moiety in a (4)H3 conformation, similar to
      the oxocarbenium ion-like conformation expected of the transition state. The
      numerous interactions formed between the (4)H3 structure and beta-galactosidase
      indicate that this structure is representative of the transition state. This
      conformation is also very similar to that of d-galactono-1,5-lactone, a good
      transition state analog. Evidence indicates that substrates take up the (4)H3
      conformation during migration from the shallow to the deep mode. Steric forces
      utilizing His418 and other residues are important for positioning the O1 leaving
      group into a quasi-axial position. An electrostatic interaction between the O5 of
      the distorted Gal and Tyr503 as well as C-H-pi bonds with Trp568 are also
      significant. Computational studies of the energy of sugar ring distortion show
      that the beta-galactosidase reaction itinerary is driven by energetic
      considerations in utilization of a (4)H3 transition state with a novel (4)C1
      (4)H3-(4)C1 conformation itinerary. To our knowledge, this is the first X-ray
      crystallographic structural demonstration that the transition state of a natural
      substrate of a glycosidase has a (4)H3 conformation.

PMID- 26291714
TI  - Tissue Inhibitor of Metalloproteinase-4 Triggers Apoptosis in Cervical Cancer
      Cells.
AB  - Tissue inhibitor of metalloproteinase-4 (TIMP-4) is a member of extracellular
      matrix (ECM) metalloproteinases inhibitors that has pleiotropic functions.
      However, TIMP-4 roles in carcinogenesis are not well understood. Cell viability
      and flow cytometer assays were employed to evaluate cell death differences
      between H-Vector and H-TIMP-4 cell lines. Immunobloting and semi-quantitative RT
      PCR were used to evaluate the expression of apoptosis regulators. We showed that
      TIMP-4 has apoptosis-sensitizing effects towards several death stimuli.
      Consistent with these findings, regulators of apoptosis from Inhibitors of
      Apoptosis Proteins (IAP), FLICE-like inhibitor proteins (FLIP) and Bcl-2 family
      members were modulated by TIMP-4. In addition, TIMP-4 knockdown resulted in cell
      survival increase after serum deprivation, as assessed by clonogenic cell
      analyses. This report shows that TIMP-4 regulates carcinogenesis through
      apoptosis activation in cervical cancer cells. Understanding TIMP-4 effects in
      tumorigenesis may provide clues for future therapies. 

PMID- 26291715
TI  - Radiation-Induced Liver Injury in Three-Dimensional Conformal Radiation Therapy
      (3D-CRT) for Postoperative or Locoregional Recurrent Gastric Cancer: Risk Factors
      and Dose Limitations.
AB  - PURPOSE: This study examined the status of radiation-induced liver injury in
      adjuvant or palliative gastric cancer radiation therapy (RT), identified risk
      factors of radiation-induced liver injury in gastric cancer RT, analysed the dose
      volume effects of liver injury, and developed a liver dose limitation reference
      for gastric cancer RT. METHODS AND MATERIALS: Data for 56 post-operative gastric
      cancer patients and 6 locoregional recurrent gastric cancer patients treated with
      three-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated
      radiation therapy (IMRT) from Sep 2007 to Sep 2009 were analysed. Forty patients
      (65%) were administered concurrent chemotherapy. Pre- and post-radiation
      chemotherapy were given to 61 patients and 43 patients, respectively. The
      radiation dose was 45-50.4 Gy in 25-28 fractions. Clinical parameters, including
      gender, age, hepatic B virus status, concurrent chemotherapy, and the total
      number of chemotherapy cycles, were included in the analysis. Univariate analyses
      with a non-parametric rank test (Mann-Whitney test) and logistic regression test
      and a multivariate analysis using a logistic regression test were completed. We
      also analysed the correlation between RT and the changes in serum chemistry
      parameters [including total bilirubin, (TB), direct bilirubin (D-TB), alkaline
      phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase
      (AST) and serum albumin (ALB)] after RT. RESULTS: The Child-Pugh grade progressed
      from grade A to grade B after radiotherapy in 10 patients. A total of 16 cases of
      classic radiation-induced liver disease (RILD) were observed, and 2 patients had
      both Child-Pugh grade progression and classic RILD. No cases of non-classic
      radiation liver injury occurred in the study population. Among the tested
      clinical parameters, the total number of chemotherapy cycles correlated with
      liver function injury. V35 and ALP levels were significant predictive factors for
      radiation liver injury. CONCLUSIONS: In 3D-CRT for gastric cancer patients,
      radiation-induced liver injury may occur and affect the overall treatment plan.
      The total number of chemotherapy cycles correlated with liver function injury,
      and V35 and ALP are significant predictive factors for radiation-induced liver
      injury. Our dose limitation reference for liver protection is feasible.

PMID- 26291717
TI  - Band Edge Energetics of Heterostructured Nanorods: Photoemission Spectroscopy and
      Waveguide Spectroelectrochemistry of Au-Tipped CdSe Nanorod Monolayers.
AB  - Conduction and valence band energies (ECB, EVB) for CdSe nanorods (NRs)
      functionalized with Au nanoparticle (NP) tips are reported here, referenced to
      the vacuum scale. We use (a) UV photoemission spectroscopy (UPS) to measure EVB
      for NR films, utilizing advanced approaches to secondary electron background
      correction, satellite removal to enhance spectral contrast, and correction for
      shifts in local vacuum levels; and (b) waveguide-based spectroelectrochemistry to
      measure ECB from onset potentials for electron injection into NR films tethered
      to ITO. For untipped CdSe NRs, both approaches show EVB = 5.9-6.1 eV and ECB =
      4.1-4.3 eV. Addition of Au tips alters the NR band edge energies and introduces
      midgap states, in ways that are predicted to influence the efficiency of these
      nanomaterials as photoelectrocatalysts. UPS results show that Au tipping shifts
      EVB closer to vacuum by up to 0.4 eV, shifts the apparent Fermi energy toward the
      middle of the band gap, and introduces additional states above EVB.
      Spectroelectrochemical results confirm these trends: Au tipping shifts ECB closer
      to vacuum, by 0.4-0.6 eV, and introduces midgap states below ECB, which are
      assigned as metal-semiconductor interface (MSI) states. Characterization of these
      band edge energies and understanding the origins of MSI states is needed to
      design energy conversion systems with proper band alignment between the light
      absorbing NR, the NP catalyst, and solution electron donors and acceptors. The
      complementary characterization protocols presented here should be applicable to a
      wide variety of thin films of heterogeneous photoactive nanomaterials, aiding in
      the identification of the most promising material combinations for
      photoelectrochemical energy conversion. 

PMID- 26291716
TI  - Sex Differences in Dose Escalation and Overdose Death during Chronic Opioid
      Therapy: A Population-Based Cohort Study.
AB  - BACKGROUND: The use of opioids for noncancer pain is widespread, and more than
      16,000 die of opioid-related causes in the United States annually. The patients
      at greatest risk of death are those receiving high doses of opioids. Whether sex
      influences the risk of dose escalation or opioid-related mortality is unknown.
      METHODS AND FINDINGS: We conducted a cohort study using healthcare records of
      32,499 individuals aged 15 to 64 who commenced chronic opioid therapy for
      noncancer pain between April 1, 1997 and December 31, 2010 in Ontario, Canada.
      Patients were followed from their first opioid prescription until discontinuation
      of therapy, death from any cause or the end of the study period. Among patients
      receiving chronic opioid therapy, 589 (1.8%) escalated to high dose therapy and n
      = 59 (0.2%) died of opioid-related causes while on treatment. After multivariable
      adjustment, men were more likely than women to escalate to high-dose opioid
      therapy (adjusted hazard ratio 1.44; 95% confidence interval 1.21 to 1.70) and
      twice as likely to die of opioid-related causes (adjusted hazard ratio 2.04; 95%
      confidence interval 1.18 to 3.53). These associations were maintained in a
      secondary analysis of 285,520 individuals receiving any opioid regardless of the
      duration of therapy. CONCLUSIONS: Men are at higher risk than women for
      escalation to high-dose opioid therapy and death from opioid-related causes. Both
      outcomes were more common than anticipated.

PMID- 26291718
TI  - Complete Genome Sequence of Mulberry Vein Banding Associated Virus, a New
      Tospovirus Infecting Mulberry.
AB  - Mulberry vein banding associated virus (MVBaV) that infects mulberry plants with
      typical vein banding symptoms had been identified as a tentative species of the
      genus Tospovirus based on the homology of N gene sequence to those of
      tospoviruses. In this study, the complete sequence of the tripartite RNA genome
      of MVBaV was determined and analyzed. The L RNA has 8905 nucleotides (nt) and
      encodes the putative RNA-dependent RNA polymerase (RdRp) of 2877 aa amino acids
      (aa) in the viral complementary (vc) strand. The RdRp of MVBaV shares the highest
      aa sequence identity (85.9%) with that of Watermelon silver mottle virus (WSMoV),
      and contains conserved motifs shared with those of the species of the genus
      Tospovirus. The M RNA contains 4731 nt and codes in ambisense arrangement for the
      NSm protein of 309 aa in the sense strand and the Gn/Gc glycoprotein precursor
      (GP) of 1,124 aa in the vc strand. The NSm and GP of MVBaV share the highest aa
      sequence identities with those of Capsicum chlorosis virus (CaCV) and Groundnut
      bud necrosis virus (GBNV) (83.2% and 84.3%, respectively). The S RNA is 3294 nt
      in length and contains two open reading frames (ORFs) in an ambisense coding
      strategy, encoding a 439-aa non-structural protein (NSs) and the 277-aa
      nucleocapsid protein (N), respectively. The NSs and N also share the highest aa
      sequence identity (71.1% and 74.4%, respectively) with those of CaCV.
      Phylogenetic analysis of the RdRp, NSm, GP, NSs, and N proteins showed that MVBaV
      is most closely related to CaCV and GBNV and that these proteins cluster with
      those of the WSMoV serogroup, and that MVBaV seems to be a species bridging the
      two subgroups within the WSMoV serogroup of tospoviruses in evolutionary aspect,
      suggesting that MVBaV represents a distinct tospovirus. Analysis of S RNA
      sequence uncovered the highly conserved 5'-/3'-ends and the coding regions, and
      the variable region of IGR with divergent patterns among MVBaV isolates. 

PMID- 26291719
TI  - Students' unchanging smoking habits in urban and rural areas in the last 15
      years.
AB  - BACKGROUND: Smoking is the main preventable public health problem particularly
      for youth worldwide. The aim of the present study was to determine the prevalence
      of smoking habits among students at secondary and high schools, and to compare
      the findings with those of a study conducted 15 years ago in the same area.
      METHODS: In this cross-sectional study 6212 students (51.2% female; 48.8% male)
      were selected randomly from rural and urban areas in Samsun. All students
      completed a face-to-face questionnaire. RESULTS: The overall prevalence of
      smoking was 13.0% (male students, 18.1%; female students, 8.2%). The mean
      starting age of smoking was 14.1 +/- 1.5 years. Prevalence of smoking was 15.7%
      in urban areas and 8.1% in rural areas. The most important factors for starting
      smoking were social group and families. Compared with a study conducted 15 years
      previously in the same area for male students, smoking prevalence was increased
      in rural, but decreased in urban areas. CONCLUSIONS: Smoking prevalence in
      students in Samsun was similar to that in a study conducted 15 years previously.
      It is important to use anti-smoking campaigns directly targeted at teenager and
      they should be fully informed of the harmful effects of smoking.

PMID- 26291720
TI  - Strongly Coupled Quantum Heat Machines.
AB  - Energy conversion of heat into work at the quantum level is modeled by quantum
      heat machines (QHMs) generally assumed to operate at weak coupling to the baths.
      This supposition is grounded in the separability principle between systems and
      allows the derivation of the evolution equation. In the weak coupling regime, the
      machine's output is limited by the coupling strength, restricting their
      application. Seeking to overcome this limitation, we analyze QHMs in the
      virtually unexplored strong coupling regime here, where separability, as well as
      other standard thermodynamic assumptions, may no longer hold. We show that
      strongly coupled QHMs may be as efficient as their weakly coupled counterparts.
      In addition, we find a novel turnover behavior where their output saturates and
      disappears in the limit of ultrastrong coupling. 

PMID- 26291721
TI  - Science of Water Leaks: Validated Theory for Moisture Flow in Microchannels and
      Nanochannels.
AB  - Water is ubiquitous; the science of its transport in micro- and nanochannels has
      applications in electronics, medicine, filtration, packaging, and earth and
      planetary science. Validated theory for water vapor and two-phase water flows is
      a "missing link"; completing it enables us to define and quantify flow in a set
      of four standard leak configurations with dimensions from the nanoscale to the
      microscale. Here we report the first measurements of water vapor flow rates
      through four silica microchannels as a function of humidity, including under
      conditions when air is present as a background gas. An important finding is that
      the tangential momentum accommodation coefficient (TMAC) is strongly modified by
      surface layers of adsorbed water molecules, in agreement with previous work on
      the TMAC for nitrogen molecules impacting a silica surface in the presence of
      moisture. We measure enhanced flow rates for two-phase flows in silica
      microchannels driven by capillary filling. For the measurement of flows in
      nanochannels we use heavy water mass spectrometry. We construct the theory for
      the flow rates of the dominant modes of water transport through each of the four
      standard configurations and benchmark it against our new measurements in silica
      and against previously reported measurements for nanochannels in carbon
      nanotubes, carbon nanopipes, and porous alumina. The findings show that all
      behavior can be described by the four standard leak configurations and that
      measurements of leak behavior made using other molecules, such as helium, are not
      reliable. Single-phase water vapor flow is overestimated by a helium measurement,
      while two-phase flows are greatly underestimated for channels larger than 100 nm
      or for all channels when boundary slip applies, to an extent that depends on the
      slip length for the liquid-phase flows. 

PMID- 26291722
TI  - Structural Model of the Bilitranslocase Transmembrane Domain Supported by NMR and
      FRET Data.
AB  - We present a 3D model of the four transmembrane (TM) helical regions of
      bilitranslocase (BTL), a structurally uncharacterized protein that transports
      organic anions across the cell membrane. The model was computed by considering
      helix-helix interactions as primary constraints, using Monte Carlo simulations.
      The interactions between the TM2 and TM3 segments have been confirmed by Forster
      resonance energy transfer (FRET) spectroscopy and nuclear magnetic resonance
      (NMR) spectroscopy, increasing our confidence in the model. Several insights into
      the BTL transport mechanism were obtained by analyzing the model. For example,
      the observed cis-trans Leu-Pro peptide bond isomerization in the TM3 fragment may
      indicate a key conformational change during anion transport by BTL. Our
      structural model of BTL may facilitate further studies, including drug discovery.

PMID- 26291723
TI  - Trypanosomes Modify the Behavior of Their Insect Hosts: Effects on Locomotion and
      on the Expression of a Related Gene.
AB  - BACKGROUND: As a result of evolution, the biology of triatomines must have been
      significantly adapted to accommodate trypanosome infection in a complex network
      of vector-vertebrate-parasite interactions. Arthropod-borne parasites have
      probably developed mechanisms, largely still unknown, to exploit the vector
      vertebrate host interactions to ensure their transmission to suitable hosts.
      Triatomines exhibit a strong negative phototaxis and nocturnal activity, believed
      to be important for insect survival against its predators. METHODOLOGY/PRINCIPAL
      FINDINGS: In this study we quantified phototaxis and locomotion in starved fifth
      instar nymphs of Rhodnius prolixus infected with Trypanosoma cruzi or Trypanosoma
      rangeli. T. cruzi infection did not alter insect phototaxis, but induced an
      overall 20% decrease in the number of bug locomotory events. Furthermore, the
      significant differences induced by this parasite were concentrated at the
      beginning of the scotophase. Conversely, T. rangeli modified both behaviors, as
      it significantly decreased bug negative phototaxis, while it induced a 23%
      increase in the number of locomotory events in infected bugs. In this case, the
      significant effects were observed during the photophase. We also investigated the
      expression of Rpfor, the triatomine ortholog of the foraging gene known to
      modulate locomotion in other insects, and found a 4.8 fold increase for T.
      rangeli infected insects. CONCLUSIONS/SIGNIFICANCE: We demonstrated for the first
      time that trypanosome infection modulates the locomotory activity of the
      invertebrate host. T. rangeli infection seems to be more broadly effective, as
      besides affecting the intensity of locomotion this parasite also diminished
      negative phototaxis and the expression of a behavior-associated gene in the
      triatomine vector.

PMID- 26291725
TI  - Acute and chronic role of nitric oxide, renin-angiotensin system and sympathetic
      nervous system in the modulation of calcium sensitization in Wistar rats.
AB  - Principal vasoactive systems - renin-angiotensin system (RAS), sympathetic
      nervous system (SNS), nitric oxide (NO) and prostanoids - exert their vascular
      effects through the changes in calcium levels and/or calcium sensitization. To
      estimate a possible modulation of calcium sensitization by the above vasoactive
      systems, we studied the influence of acute and chronic blockade of particular
      vasoactive systems on blood pressure (BP) changes elicited in conscious
      normotensive rats by acute dose-dependent administration of Rho-kinase inhibitor
      fasudil. Adult male chronically cannulated Wistar rats were used throughout this
      study. The acute inhibition of NO synthase (NOS) by L-NAME enhanced BP response
      to fasudil, the effect being considerably augmented in rats deprived of
      endogenous SNS. The acute inhibition of prostanoid synthesis by indomethacin
      modified BP response to fasudil less than the acute NOS inhibition. The chronic
      NOS inhibition caused moderate BP elevation and a more pronounced augmentation of
      fasudil-induced BP changes compared to the effect of acute NOS inhibition. This
      indicates both short-term and long-term NO-dependent attenuation of calcium
      sensitization. Long-term inhibition of RAS by captopril caused a significant
      attenuation of BP changes elicited by fasudil. In contrast, a long-term
      attenuation of SNS by chronic guanethidine treatment (in youth or adulthood) had
      no effect on BP response to fasudil, suggesting the absence of SNS does not
      affect calcium sensitization in vascular smooth muscle of normotensive rats. In
      conclusion, renin-angiotensin system contributes to the long-term increase of
      calcium sensitization and its effect is counterbalanced by nitric oxide which
      decreases calcium sensitization in Wistar rats. 

PMID- 26291724
TI  - Engraftment of Human Glioblastoma Cells in Immunocompetent Rats through Acquired
      Immunosuppression.
AB  - Transplantation of glioblastoma patient biopsy spheroids to the brain of T cell
      compromised Rowett (nude) rats has been established as a representative animal
      model for human GBMs, with a tumor take rate close to 100%. In immunocompetent
      littermates however, primary human GBM tissue is invariably rejected. Here we
      show that after repeated passaging cycles in nude rats, human GBM spheroids are
      enabled to grow in the brain of immunocompetent rats. In case of engraftment,
      xenografts in immunocompetent rats grow progressively and host leukocytes fail to
      enter the tumor bed, similar to what is seen in nude animals. In contrast,
      rejection is associated with massive infiltration of the tumor bed by leukocytes,
      predominantly ED1+ microglia/macrophages, CD4+ T helper cells and CD8+ effector
      cells, and correlates with elevated serum levels of pro-inflammatory cytokines IL
      1alpha, IL-18 and TNF-alpha [corrected]. We observed that in nude rat brains, an
      adaptation to the host occurs after several in vivo passaging cycles,
      characterized by striking attenuation of microglial infiltration. Furthermore,
      tumor-derived chemokines that promote leukocyte migration and their entry into
      the CNS such as CXCL-10 and CXCL-12 are down-regulated, and the levels of TGF
      beta2 increase. We propose that through serial in vivo passaging in nude rats,
      human GBM cells learn to avoid and or/ suppress host immunity. Such adapted GBM
      cells are in turn able to engraft in immunocompetent rats without signs of an
      inflammatory response.

PMID- 26291726
TI  - Ellagitannins--compounds from pomegranate as possible effector in steroidogenesis
      of rabbit ovaries.
AB  - This study has observed possible effect of ellagitannins - compounds from
      pomegranate on process of steroidogenesis in ovaries. The aim of the study was to
      investigate the possible effect of punicalagin on secretion of steroid hormones -
      progesterone, androstenedione, testosterone and 17beta-estradiol by ovarian
      fragments of rabbits in vitro. Ovarian fragments from sexually mature female New
      Zealand white rabbits (n=20) were incubated without (control group) or with
      punicalagin at various doses 1, 10 and 100 microg.ml(-1) for 24 h. Hormones were
      evaluated by ELISA (The Enzyme-Linked Immunosorbent Assay). Data showed that
      progesterone and 17beta-estradiol (but not androstenedione and testosterone)
      release by rabbit ovarian fragments was significantly affected by punicalagin
      addition at various doses. Punicalagin (at 100 microg.ml(-1)) significantly
      (P<0.05) increased progesterone secretion. On the other hand, the release of
      17beta-estradiol was significantly (P<0.005) decreased by punicalagin addition
      (at 10 microg.ml(-1)). Our results suggest that punicalagin could have dose
      dependent impact on secretion of steroid hormones progesterone and 17beta
      estradiol by rabbit ovarian fragments and it may be effector in process of
      ovarian steroidogenesis. 

PMID- 26291727
TI  - A novel carboxymethylated mercaptotriazinoindole inhibitor of aldose reductase
      interferes with the polyol pathway in streptozotocin-induced diabetic rats.
AB  - The aim of the present work was to study the effect of 3-mercapto-5H-1,2,4
      triazino[5,6-b]indole-5-acetic acid (CMTI), an efficient aldose reductase
      inhibitor, on sorbitol accumulation in selected organs of streptozotocin-induced
      diabetic rats in vivo. In addition, the effect of CMTI on aldose reductase back
      reaction and on sorbitol dehydrogenase was determined. The model of experimental
      diabetes in male Wistar rats induced by streptozotocin was used. Experimental
      diabetes was induced by triple intraperitoneal doses of streptozotocin on three
      consecutive days. In diabetic rats, significant elevation of sorbitol
      concentration in the sciatic nerve and eye lenses was recorded. CMTI administered
      intragastrically (50 mg/kg/day) for five consecutive days significantly inhibited
      sorbitol accumulation in the sciatic nerve, yet it was without effect in eye
      lenses of diabetic animals. For aldose reductase back reaction, the substrate
      affinity of glycerol to aldose reductase was one order lower than that of
      glyceraldehyde in forward reaction. In addition, the back reaction was much
      slower, characterized by V(max) value of about 30 times lower than that of the
      forward reaction. Inhibition of aldose reductase by CMTI was characterized by
      closely related IC(50) values in submicromolar range for both forward and back
      reactions. No significant inhibition of the second enzyme of the polyol pathway,
      sorbitol dehydrogenase, by 100 microM CMTI was recorded (I=0.9+/-2.7 %, n=3). To
      conclude, the presented results showed the ability of CMTI to affect the polyol
      pathway in diabetic rats in vivo and represent thus a further step in a complex
      preclinical evaluation of CMTI as a potential agent for treatment of chronic
      diabetic complications. 

PMID- 26291728
TI  - A Case of Malignant Hyperthermia Captured by Neuromonitoring During a Lumbar
      Endoscopic Discectomy.

PMID- 26291729
TI  - Adverse Hemodynamic Event Due to Floseal Hemostatic Matrix Application.

PMID- 26291730
TI  - Hydrodecarboxylation of Carboxylic and Malonic Acid Derivatives via Organic
      Photoredox Catalysis: Substrate Scope and Mechanistic Insight.
AB  - A direct, catalytic hydrodecarboxylation of primary, secondary, and tertiary
      carboxylic acids is reported. The catalytic system consists of a Fukuzumi
      acridinium photooxidant with phenyldisulfide acting as a redox-active cocatalyst.
      Substoichiometric quantities of Hunig's base are used to reveal the carboxylate.
      Use of trifluoroethanol as a solvent allowed for significant improvements in
      substrate compatibilities, as the method reported is not limited to carboxylic
      acids bearing alpha heteroatoms or phenyl substitution. This method has been
      applied to the direct double decarboxylation of malonic acid derivatives, which
      allows for the convenient use of dimethyl malonate as a methylene synthon.
      Kinetic analysis of the reaction is presented showing a lack of a kinetic isotope
      effect when generating deuterothiophenol in situ as a hydrogen atom donor.
      Further kinetic analysis demonstrated first-order kinetics with respect to the
      carboxylate, while the reaction is zero-order in acridinium catalyst, consistent
      with another finding suggesting the reaction is light limiting and carboxylate
      oxidation is likely turnover limiting. Stern-Volmer analysis was carried out in
      order to determine the efficiency for the carboxylates to quench the acridinium
      excited state. 

PMID- 26291731
TI  - Optically transparent carbon nanotube film electrode for thin layer
      spectroelectrochemistry.
AB  - Carbon nanotube (CNT) film was evaluated as an optically transparent electrode
      (OTE) for thin layer spectroelectrochemistry. Chemically inert CNT arrays were
      synthesized by chemical vapor deposition (CVD) using thin films of Fe and Co as
      catalysts. Vertically aligned CNT arrays were drawn onto a quartz slide to form
      CNT films that constituted the OTE. Adequate conductivity and transparency make
      this material a good OTE for spectroelectrochemistry. These properties could be
      varied by the number of layers of CNTs used to form the OTE. Detection in the
      UV/near UV region down to 200 nm can be achieved using these transparent CNT
      films on quartz. The OTE was characterized by transmission electron microscopy,
      scanning electron microscopy, Raman spectroscopy, UV-visible spectroscopy, cyclic
      voltammetry, electrochemical impedance spectroscopy, and thin layer
      spectroelectrochemistry. Ferricyanide, tris(2,2'-bipyridine) ruthenium(II)
      chloride, and cytochrome c were used as representative redox probes for thin
      layer spectroelectrochemistry using the CNT film OTE, and the results correlated
      well with their known properties. Direct electron transfer of cytochrome c was
      achieved on the CNT film electrode. 

PMID- 26291732
TI  - Copper-Catalyzed N-Benzoylation of Amines via Aerobic C-C Bond Cleavage.
AB  - A general copper/air catalytic system for selectively oxidative C-C bond cleavage
      of 1,2-diarylethan-1-one has been developed, giving aromatic aldehydes and N
      benzoylation products of various amines in moderate to excellent yields. This
      research provides an alternative approach for the N-benzoylation of amine in mild
      and neutral conditions. 

PMID- 26291733
TI  - P(NMe2)3-mediated reductive [1+4] annulation of isatins with enones: a facile
      synthesis of spirooxindole-dihydrofurans.
AB  - A novel P(NMe2)3-mediated reductive [1+4] annulation reaction between isatins and
      enones has been developed, providing the facile synthesis of spirooxindole
      dihydrofurans. This reaction unveils the first practical approach to construct
      five-membered cyclic motifs via a Kukhtin-Ramirez adduct involved [1+4]
      annulation mode. 

PMID- 26291734
TI  - Alternatives to the fixed-set model: A review of appraisal models of emotion.
AB  - Over several decades, appraisal theory has emerged as a prominent theoretical
      framework explaining the elicitation and differentiation of emotions, and has
      stimulated a great deal of theorising and empirical research. Despite the large
      amount of research in this area, there are many aspects of appraisal theory and
      research that remain unclear or problematic. In this review, we identify a common
      assumption of many appraisal theories-the fixed appraisal set-and argue that this
      assumption, combined with a lack of explicit theorising about the predicted
      relationship between appraisals and emotions, leads to a lack of clarity in both
      appraisal models and the empirical testing of those models. We recommend that
      appraisal theorists move in a direction already taken by a small number of
      theorists, and adopt the starting assumption of a variable appraisal set. We
      further suggest that theories of concepts and categorisation may inform
      theorising about appraisal-emotion relationships.

PMID- 26291735
TI  - Breastfeeding as an Exposure Pathway for Perfluorinated Alkylates.
AB  - Perfluorinated alkylate substances (PFASs) are widely used and have resulted in
      human exposures worldwide. PFASs occur in breast milk, and the duration of
      breastfeeding is associated with serum-PFAS concentrations in children. To
      determine the time-dependent impact of this exposure pathway, we examined the
      serum concentrations of five major PFASs in a Faroese birth cohort at birth, and
      at ages 11, 18, and 60 months. Information about the children's breastfeeding
      history was obtained from the mothers. The trajectory of serum-PFAS
      concentrations during months with and without breastfeeding was examined by
      linear mixed models that accounted for the correlations of the PFAS measurements
      for each child. The models were adjusted for confounders such as body size. The
      duration of exclusive breastfeeding was associated with increases of most PFAS
      concentrations by up to 30% per month, with lower increases during partial breast
      feeding. In contrast to this main pattern, perfluorohexanesulfonate was not
      affected by breast-feeding. After cessation of breastfeeding, all serum
      concentrations decreased. This finding supports the evidence of breastfeeding
      being an important exposure pathway to some PFASs in infants. 

PMID- 26291736
TI  - Effect of Culture-Independent Diagnostic Tests on Future Emerging Infections
      Program Surveillance.
AB  - The Centers for Disease Control and Prevention Emerging Infections Program (EIP)
      network conducts population-based surveillance for pathogens of public health
      importance. Central to obtaining estimates of disease burden and tracking
      microbiological characteristics of these infections is accurate laboratory
      detection of pathogens. The use of culture-independent diagnostic tests (CIDTs)
      in clinical settings presents both opportunities and challenges to EIP
      surveillance. Because CIDTs offer better sensitivity than culture and are
      relatively easy to perform, their use could potentially improve estimates of
      disease burden. However, changes in clinical testing practices, use of tests with
      different sensitivities and specificities, and changes to case definitions make
      it challenging to monitor trends. Isolates are still needed for performing strain
      typing, antimicrobial resistance testing, and identifying other molecular
      characteristics of organisms. In this article, we outline current and future EIP
      activities to address issues associated with adoption of CIDTs, which may apply
      to other public health surveillance. 

PMID- 26291737
TI  - In Vitro Radiosensitization of Esophageal Cancer Cells with the Aminopeptidase
      Inhibitor CHR-2797.
AB  - With the increased incidence of esophageal cancer, chemoradiotherapy continues to
      play an important role in the management of this disease. Developing potent
      radiosensitizers is therefore critical for improving outcomes. The use of drugs
      that have already undergone clinical testing is an appealing approach once the
      side effects and tolerated doses are established. Here, we demonstrate that the
      aminopeptidase inhibitor, CHR-2797/tosedostat, increases the radiosensitivity of
      esophageal cancer cell lines (FLO-1 and OE21) in vitro in both normoxic and
      physiologically relevant low oxygen conditions. To our knowledge, the effective
      combination of CHR-2797 with radiation exposure has not been reported previously
      in any cancer cell type. The mechanism of increased radiosensitivity was not
      dependent on the induction of DNA damage or DNA repair kinetics. Our data support
      the need for further preclinical testing of CHR-2797 in combination with
      radiotherapy for the treatment of esophageal cancer. 

PMID- 26291738
TI  - The Effect of Fermented Papaya Preparation on Radioactive Exposure.
AB  - Exposure to ionizing radiation causes cellular damage, which can lead to
      premature cell death or accumulation of somatic mutations, resulting in
      malignancy. The damage is mediated in part by free radicals, particularly
      reactive oxygen species. Fermented papaya preparation (FPP), a product of yeast
      fermentation of Carica papaya Linn, has been shown to act as an antioxidant. In
      this study, we investigated the potential of FPP to prevent radiation-induced
      damage. FPP (0-100 MUg/ml) was added to cultured human foreskin fibroblasts and
      myeloid leukemia (HL-60) cells either before or after irradiation (0-18 Gy).
      After 1-3 days, the cells were assayed for: intracellular labile iron, measured
      by staining with calcein; reactive oxygen species generation, measured with
      dichlorofluorescein diacetate; apoptosis, determined by phosphatidylserine
      exposure; membrane damage, determined by propidium iodide uptake; and cell
      survival, determined by a cell proliferation assay. DNA damage was estimated by
      measuring 8-oxoguanine, a parameter of DNA oxidation, using a fluorescent
      specific probe and by the comet assay. These parameters were also assayed in bone
      marrow cells of mice treated with FPP (by adding it to the drinking water) either
      before or after irradiation. Somatic mutation accumulation was determined in
      their peripheral red blood cells, and their survival was monitored. FPP
      significantly reduced the measured radiation-induced cytotoxic parameters. These
      findings suggest that FPP might serve as a radioprotector, and its effect on DNA
      damage and mutagenicity might reduce the long-term effects of radiation, such as
      primary and secondary malignancy. 

PMID- 26291739
TI  - Complete mitochondrial genome of four pheretimoid earthworms (Clitellata:
      Oligochaeta) and their phylogenetic reconstruction.
AB  - Among oligochaetes, the Pheretima complex within the Megascolecidae is a major
      earthworm group. Recently, however, the systematics of the Pheretima complex
      based on morphology are challenged by molecular studies. Since little comparative
      analysis of earthworm complete mitochondrial genomes has been reported yet, we
      sequenced mitogenomes of four pheretimoid earthworm species to explore their
      phylogenetic relationships. The general earthworm genomic features are also found
      in four earthworms: all genes transcribed from the same strand, the same
      initiation codon ATG for each PCGs, and conserved structures of RNA genes.
      Interestingly we find an extra potential tRNA-leucine (CUN) in Amynthas
      longisiphonus. The earthworm mitochondrial ATP8 exhibits the highest evolutionary
      rate, while the gene CO1 evolves slowest. Phylogenetic analysis based on protein
      coding genes (PCGs) strongly supports the monophyly of the Clitellata, Hirudinea,
      Oligochaeta, Megascolecidae and Pheretima complex. Our analysis, however, reveals
      non-monophyly within the genara Amynthas and Metaphire. Thus the generic
      divisions based on morphology in the Pheretima complex should be reconsidered.

PMID- 26291741
TI  - Comparison of Ganglion Cell and Retinal Nerve Fiber Layer Thickness in Pigment
      Dispersion Syndrome, Pigmentary Glaucoma, and Healthy Subjects with Spectral
      domain OCT.
AB  - PURPOSE: To evaluate the ganglion cell complex (GCC) and retinal nerve fiber
      layer (RNFL) thickness in pigment dispersion syndrome (PDS) and pigmentary
      glaucoma (PG) with RTVue spectral domain optical coherence tomography (SD-OCT).
      METHODS: A total of 102 subjects were enrolled: 29 with PDS, 18 with PG, and 55
      normal subjects. Full ophthalmic examination including visual field analysis was
      performed. SD-OCT was used to analyze GCC superior, GCC inferior, and average
      RNFL thickness. To compare the discrimination capabilities, the areas under the
      receiver operating characteristic curves were assessed. RESULTS: Superior GCC,
      inferior GCC, and RNFL thickness values of patients with PG were statistically
      signicantly lower than those of patients with PDS (p < 0.001) and healthy
      individuals (p < 0.001 for all). No statistically significant difference was
      found between PDS and normal subjects in same parameters (p > 0.05). CONCLUSIONS:
      The SD-OCT-derived GCC and RNFL thickness parameters can be useful to
      discriminate PG from both PDS and normal subjects.

PMID- 26291742
TI  - In utero exposure of mice to diesel exhaust particles affects spatial learning
      and memory with reduced N-methyl-D-aspartate receptor expression in the
      hippocampus of male offspring.
AB  - Diesel exhaust consists of diesel exhaust particles (DEPs) and gaseous compounds.
      Previous studies reported that in utero exposure to diesel exhaust affects the
      central nervous system. However, there was no clear evidence that these effects
      were caused by diesel exhaust particles themselves, gaseous compounds, or both.
      Here, we explored the effects of in utero exposure to DEPs on learning and memory
      in male ICR mice. DEP solutions were administered subcutaneously to pregnant ICR
      mice at a dose of 0 or 200 MUg/kg body weight on gestation days 6, 9, 12, 15, and
      18. We examined learning and memory in 9-to-10-week-old male offspring using the
      Morris water maze test and passive avoidance test. Immediately after the
      behavioral tests, hippocampi were isolated. Hippocampal N-methyl-D-aspartate
      receptor (NR) expression was also measured by quantitative RT-PCR analysis. Mice
      exposed to DEPs in utero showed deficits in the Morris water maze test, but their
      performance was not significantly different from that of control mice in the
      passive avoidance test. In addition, DEP-exposed mice exhibited decreased
      hippocampal NR2A expression. The present results indicate that maternal DEP
      exposure disrupts learning and memory in male offspring, which is associated with
      reduced hippocampal NR2A expression.

PMID- 26291740
TI  - Immunizations in solid organ and hematopoeitic stem cell transplant patients: A
      comprehensive review.
AB  - The Solid Organ Transplantation (SOT) and Haematopoietic Stem Cell
      Transplantation (HSCT) population is continuously increasing as a result of
      broader indications for transplant and improved survival. Infectious diseases,
      including vaccine-preventable diseases, are a significant threat for this
      population, primarily after but also prior to transplantation. As a consequence,
      clinicians must ensure that patients are optimally immunized before
      transplantation, to provide the best protection during the early post
      transplantation period, when immunosuppression is the strongest and vaccine
      responses are poor. After 3-6 months, inactivated vaccines immunization can be
      resumed. By contrast, live-attenuated vaccines are lifelong contraindicated in
      SOT patients, but can be considered in HSCT patients at least 2 years after
      transplantation, if there is no immunosuppression or graft-versus-host-disease.
      However, because of the advantages of live-attenuated over inactivated vaccines-
      and also sometimes the absence of an inactivated alternative--an increasing
      number of prospective studies on live vaccine immunization after transplantation
      are performed and give new insights about safety and immunogenicity in this
      population.

PMID- 26291743
TI  - Crural Bypass for Critical Lower Limb Ischemia with Omniflow II Prosthesis.
AB  - Background Reports about the use of the Omniflow II prosthesis (Bio Nova
      International, Victoria, Australia) in a crural position in patients with
      critical lower limb ischemia are rare. Methods All crural bypass operations were
      registered in a database. Primary end points of the study were amputation-free
      survival, limb salvage, and long-term patency. Results From January 2007 to
      December 2012, we implanted 27 Omniflow II prostheses in the crural position for
      critical lower limb ischemia. Of these, 12 crural bypasses were conducted with
      adjuvant distal arteriovenous fistula as a means to increase bypass flow in the
      presence of severely impaired intraoperative runoff or revision for early
      failure. Fifteen Omniflow II prosthesis bypasses were performed in the crural
      position without fistula. Overall, two patients died postoperatively. The limb
      salvage rate was 92% in the fistula group compared with 60% in the nonfistula
      group after a median observation time of 19 months in patients getting Omniflow
      prosthesis bypasses. Conclusion Omniflow II prosthesis in patients with critical
      lower limb ischemia and absence of sufficient autologous vein is durable.
      Moreover, the use of adjuvant distal arteriovenous fistula may increase the
      chance of limb salvage in this group of patients. 

PMID- 26291744
TI  - Hybrid Operation for Descending Aortic Pathologies Involving Distal Aortic Arch.
AB  - Background A combined endovascular and debranching hybrid procedure was performed
      for descending aortic pathologies involving the distal aortic arch. We reviewed
      our results of this procedure to summarize clinical experiences. Methods From
      April 2009 to April 2013, 36 patients (21 males and 15 females) underwent the
      hybrid operation. Hospital stay and complications were closely monitored after
      operation. Follow-up CT scan was performed at postoperative 3 months and 12
      months. Results The hospital stay ranged from 7 to 25 (15.1 +/- 5.0) days. The
      mean age at operation was 67.6 +/- 4.8 years (range: 60-79 years). In-hospital
      mortality and stroke rates were 2.8% (1/36) and 2.8% (1/36). At a mean follow-up
      of 22 months (4-52 months), the mortality was 0% (0/35). All remaining 35
      patients returned to normal life. During the follow-up period, one patient
      required secondary endovascular reintervention for a type 1 distal endovascular
      leak. Conclusion Hybrid repair for descending aortic pathologies involving the
      distal arch proves to be effective and safe at midterm follow-up with acceptable
      surgical risks and satisfactory results. 

PMID- 26291745
TI  - Effect of Left Atrial Reduction on Restoration and Maintenance of Sinus Rhythm in
      Patients Undergoing Mitral Valve Replacement: A Pilot Study.
AB  - Background This pilot study aimed to evaluate the effectiveness of posterior left
      atrial wall plication (T-plasty) in patients with persistent atrial fibrillation
      (AF) (> 7 days) undergoing mitral valve surgery. Materials and Methods A total of
      60 patients who were scheduled for mitral valve replacement were randomly
      allocated into two groups: one would receive (Group 1; n = 32, mean age; 49.37 +/
      9.00) and one would not receive (Group 2; n = 28; mean age 48.64 +/- 8.6) left
      atrial size reduction using T-plasty technique. Patients with a clear indication
      for combined procedures other than tricuspid valve disease, aortic valve disease,
      and coronary artery stenosis were not included. Follow-up was performed at 6th,
      12th, and 18th months after the operation. Results After the operation, 21
      patients (65.6%) in Group 1 and 13 patients (46.4%) in Group 2 regained sinus
      rhythm (p = 0.13). Mortality did not occur. AF recurrence rates were not
      significantly different between the groups in three follow-ups. Restoration of
      sinus rhythm was significantly more common in Group 1 patients than in Group 2
      patients during follow-up. Patients in Group 1 had lower left atrial volume
      indexes than those in Group 2 at the 6th and 12th months, whereas the difference
      at the 18th month was at the limit of significance. Conclusion We achieved
      satisfactory results using the T-plasty technique for left atrial size reduction
      in terms of mid-term restoration and preservation of normal sinus rhythm in
      patients undergoing mitral valve surgery. Further study may be justified to
      reveal the prognostic importance of the technique described herein. 

PMID- 26291746
TI  - Thoracoscopic Bilateral Bullectomy for Simultaneously Developed Bilateral Primary
      Spontaneous Pneumothorax: Ipsilateral Transmediastinal versus Bilateral
      Sequential Approach.
AB  - Background Simultaneously developed bilateral primary spontaneous pneumothorax
      (BPSP) is an indication for thoracic surgery of both sides. Recently, we have
      reported a new technique for BPSP, which is ipsilateral apicoposterior
      transmediastinal (TM) bullectomy of both sides using video-assisted thoracoscopic
      surgery (VATS), and we compared this TM VATS with bilateral sequential (BS) VATS
      for BPSP. Materials and Methods From June 2003 to May 2014, 11 and 14 patients
      were performed VATS TM and BS bullectomy for BPSP, respectively. We reviewed the
      medical records and compared the clinical data between the two groups. For TM
      group, we first performed the right VATS bullectomy and approached through the
      apicoposterior mediastinal region for contralateral VATS. In the other group,
      conventional BS VATS bullectomy was performed in the lateral decubitus position
      change. Results The mean follow-up was 62.0 +/- 32.6 months. No mortality and
      major complications were observed. The operative time (68.18 +/- 24.93 vs. 96.07
      +/- 37.73, p = 0.046), duration of left pleural drainage (1.00 +/- 0.45 vs. 3.21
      +/- 1.37, p = 0.000), and length of hospital stay (3.82 +/- 1.54 vs. 4.93 +/-
      1.07, p = 0.044) were significantly shorter in the TM group than in the BS group.
      No significant differences were seen in duration of general anesthesia, total
      number of wedge resections and endostaplers used in both lungs, duration of right
      drainage, and postoperative recurrence. Conclusion The TM VATS approach may be a
      safe and feasible modality for BPSP. It may decrease the operative time, patients
      inconvenience such as bilateral multiple wounds and longstanding placement of
      chest tubes, and decrease the hospital stay compared with the BS VATS approach.

PMID- 26291747
TI  - The Munich Lung Transplant Group: Intraoperative Extracorporeal Circulation in
      Lung Transplantation.
AB  - BACKGROUND: This retrospective single-center study aimed to analyze transfusion
      requirements, coagulation parameters, and outcome parameters in patients
      undergoing lung transplantation (LuTx) with intraoperative extracorporeal
      circulatory support, comparing cardiopulmonary bypass (CPB), and extracorporeal
      membrane oxygenation (ECMO). METHODS: Over a 3-year period, 49 of a total of 188
      LuTx recipients were identified being set intraoperatively on either conventional
      CPB (n = 22) or ECMO (n = 27). Intra- and postoperative transfusion and
      coagulation factor requirements as well as early outcome parameters were
      analyzed. RESULTS: LuTx patients on CPB had significantly higher intraoperative
      transfusion requirements when compared with ECMO patients, that is, packed red
      cells (9 units [5-18] vs. 6 units [4-8], p = 0.011), platelets (3.5 units [2-4]
      vs. 2 units [0-3], p = 0.034), fibrinogen (5 g [4-6] vs. 0 g [0-4], p = 0.013),
      prothrombin complex concentrate (3 iU [2-5] vs. 0 iU [0-2], p = 0.001), and
      tranexamic acid (2.5 mg [2-5] vs. 2.0 mg [1-3], p = 0.002). Also, ventilator
      support requirements (21 days [7-31] vs. 5 days [3-21], p = 0.013) and lengths of
      ICU stays (36 days [14-62] vs. 15 days [6-44], p = 0.030) were markedly longer in
      CPB patients. There were no differences in 30-day and 1-year mortality rates.
      CONCLUSION: These data indicate a perioperative advantage of ECMO usage with low
      dose heparinization over conventional CPB for extracorporeal circulatory support
      during LuTx. Long-term outcome is not affected.

PMID- 26291748
TI  - Ruthenium-Catalyzed Oxidant-Free Allylation of Aromatic Ketoximes with Allylic
      Acetates at Room Temperature.
AB  - Substituted aromatic ketoximes reacted efficiently with allylic acetates in the
      presence of {[RuCl2(p-cymene)]2} and AgSbF6 in 1,2-dichloroethane at ambient
      temperature, providing ortho-allyl aromatic ketoximes in a highly regioselective
      manner without an oxidant. In the reaction, the acetate group of allyl acetate
      acts as a base to activate the C-H bond of aromatics. Later, ortho-allyl aromatic
      ketoximes were converted into ortho-allyl aromatic ketones in the presence of
      HCl.

PMID- 26291749
TI  - The Hospital Anxiety and Depression Scale: a pilot study to examine its latent
      structure and the link between psychological state and symptom severity in
      transient ischaemic attack patients.
AB  - Transient ischaemic attack (TIA) is often associated with anxiety and depression,
      which may precipitate secondary stroke and interfere with treatment. The Hospital
      Anxiety and Depression Scale (HADS) is widely used to assess these states and to
      inform the management of any associated psychological problems, but there is
      considerable debate about what it actually measures. The HADS scores from a range
      of different clinical groups have been reviewed in order to assess its
      psychometric properties, but so far, no research has examined either its latent
      structure when used with TIA patients, or the association between symptom
      severity and the test's validity. The aims of this study, therefore, were to
      investigate: (a) the underlying structure of the HADS when used with TIA
      patients; and (b) the impact of symptom severity on the validity of the HADS. The
      HADS and a functional capacity measure were administered by post to a sample of
      542 confirmed TIA patients. Exploratory factor analysis was conducted on the HADS
      scores to establish its underlying structure for this clinical group, and then,
      sub-sample correlations were undertaken between the anxiety/depression scores for
      different levels of functional capacity. Two factors emerged, with 13 of the 14
      HADS items loading significantly on both, suggesting there is a common affective
      state underlying the standard anxiety and depression scales. Further data
      exploration indicated that convergence between these affective states increased
      as functional capacity deteriorated. The results suggest firstly that the HADS
      measures general subjective distress when used with TIA patients, and secondly
      that the higher reported symptom severity in this clinical group may be
      associated with reduced affective differentiation. As the ability to retain clear
      affective discrimination is associated with health and well-being, this could
      provide a focus for post-TIA rehabilitation.

PMID- 26291750
TI  - Regulation of mRNA stability by ARE-binding proteins in synaptic plasticity and
      memory.
AB  - Formation of long-term memories requires coordinated gene expression, which can
      be regulated at transcriptional, post-transcriptional, and translational levels.
      Post-transcriptional stabilization and destabilization of mRNAs provides precise
      temporal and spatial regulation of gene expression, which is critical for
      consolidation of synaptic plasticity and memory. mRNA stability is regulated by
      interactions between the cis-acting elements of mRNAs, such as adenine-uridine
      rich elements (AREs), and the trans-acting elements, ARE-binding proteins
      (AUBPs). There are several AUBPs in the nervous system. Among AUBPs, Hu/ELAV-like
      proteins and AUF1 are the most studied mRNA stabilizing and destabilizing
      factors, respectively. Here, we summarize compelling evidence for critical roles
      of these AUBPs in synaptic plasticity, as well as learning and memory, in both
      vertebrates and invertebrates. Furthermore, we also briefly review the
      deregulations of AUBPs in neurological disorders. 

PMID- 26291751
TI  - Cyphenothrin Flea and Tick Squeeze-On for Dogs: Evaluation of Potential Health
      Risks Based on the Results of Observational Biological Monitoring.
AB  - An observational biomonitoring study was conducted involving adults and children
      in households that purchased and applied a cyphenothrin-containing spot-on
      product for dogs as part of their normal pet care practices. The 3- to 6-yr-old
      children had greater exposure than the adult applicators in the same house, 3.8
      and 0.6 MUg/kg body weight, respectively. The mean measured values in children
      were 13-fold lower than those estimated using the U.S. Environmental Protection
      Agency (EPA) current standard operating procedures (SOP) for pet products
      (assuming 5% dermal absorption), although the maximum absorbed dosage of one
      child on one day was equivalent to the default value derived from the SOPs. With
      regard to potential human health risks, it can be concluded that despite the
      inherent conservatism in both the exposure and toxicology data, the margins of
      exposure (MOE) were consistently greater than 100 for average, 95th percentile,
      and maximum exposures. More specifically, the results of this study demonstrated
      that the MOE were consistently greater than 1,000 for mean exposures and exceeded
      100 for 95th percentile and maximum measured exposures, which clearly indicates a
      reasonable certainty of no harm when using the cyphenothrin spot-on products. It
      is also noteworthy that Sergeant's spot-on products containing cyphenothrin
      currently sold in the United States have lower weight percentages of active
      ingredient and lower applied amounts than those used by all but two of the
      participant households in this study. 

PMID- 26291752
TI  - A Proposed Minimum Standard Set of Outcome Measures for Cataract Surgery.
AB  - IMPORTANCE: Aligning outcome measures for cataract surgery, one of the most
      frequently performed procedures globally, may facilitate international
      comparisons that can drive improvements in the outcomes most meaningful to
      patients. OBJECTIVE: To propose a minimum standard set of outcome measures for
      cataract surgery that enables global comparisons. DESIGN, SETTING, AND
      PARTICIPANTS: A working group of international experts in cataract outcomes and
      registries was convened, along with a patient advocate, to agree on a consensus
      of outcome measures for cataract surgery. In a modified Delphi process, the group
      met regularly between November 10, 2012, and November 21, 2013, to discuss which
      outcomes to include in a standard set. Included factors were based on extant
      literature, existing registries, and the experience of group members. Similarly,
      a series of consensus discussions were held to determine a set of risk factors to
      be gathered for each patient. The final shortlist was compiled into a standard
      set. Analysis was performed from November 22, 2013, to April 5, 2014. MAIN
      OUTCOMES AND MEASURES: Development of a recommended standard set encompassing
      preoperative metrics including patient risk factors, intraoperative factors
      including surgical complications, and postoperative cataract surgery outcomes.
      RESULTS: The recommended standard set encompasses all patients treated for
      cataracts by 1 of 4 surgical approaches (phacoemulsification, sutured manual
      extracapsular cataract extraction, sutureless manual extracapsular cataract
      extraction, or intracapsular cataract extraction). The recommended metrics to be
      recorded preoperatively include demographics, ocular history and comorbidities,
      preoperative visual acuity, and patient-reported visual function. The recommended
      outcomes were split into intraoperative and postoperative metrics. Intraoperative
      outcomes include capsule-related problems, dislocation of lens nucleus fragments
      into the vitreous, and other complications. Postoperative outcomes include visual
      acuity, refractive error, patient-reported visual function, and early and late
      complications of surgery. The suggested follow-up for collection of postoperative
      outcomes is up to 3 months. CONCLUSIONS AND RELEVANCE: A minimum standard set of
      outcome measures for cataract surgery is important for meaningful comparison
      across contexts. The proposed data set is a compromise between all useful data
      and the practicalities of data collection.

PMID- 26291754
TI  - Potential Benefits of Exergaming for Cognition and Dual-Task Function in Older
      Adults: A Systematic Review.
AB  - This paper provides a systematic review of current research findings using
      exergaming as a treatment for improving cognition and dual-task function in older
      adults. A literature search was conducted to collect exergaming intervention
      studies that were either randomized controlled or uncontrolled studies. Of the
      seven identified studies (five randomized controlled studies and two uncontrolled
      studies), three studies focused on cognitive function alone, two studies focused
      on dual-task function alone, and two studies measured both cognitive function and
      dual-task function. Current evidence supports that exergaming improves cognitive
      function and dual-task function, which potentially leads to fall prevention.
      However, it is unclear whether exergaming, which involves both cognitive input
      and physical exercise, has additional benefits compared with traditional physical
      exercise alone. Further studies should include traditional exercise as a control
      group to identify these potential, additional benefits. 

PMID- 26291753
TI  - Defining the Asthma-COPD Overlap Syndrome in a COPD Cohort.
AB  - BACKGROUND: Asthma-COPD overlap syndrome (ACOS) has been recently described by
      international guidelines. A stepwise approach to diagnosis using usual features
      of both diseases is recommended although its clinical application is difficult.
      METHODS: To identify patients with ACOS, a cohort of well-characterized patients
      with COPD and up to 1 year of follow-up was analyzed. We evaluated the presence
      of specific characteristics associated with asthma in this COPD cohort, divided
      into major criteria (bronchodilator test > 400 mL and 15% and past medical
      history of asthma) and minor criteria (blood eosinophils > 5%, IgE > 100 IU/mL,
      or two separate bronchodilator tests > 200 mL and 12%). We defined ACOS by the
      presence of one major criterion or two minor criteria. Baseline characteristics,
      health status (COPD Assessment Test [CAT]), BMI, airflow obstruction, dyspnea,
      and exercise capacity (BODE) index, rate of exacerbations, and mortality up to 1
      year of follow-up were compared between patients with and without criteria for
      ACOS. RESULTS: Of 831 patients with COPD included,125 (15%) fulfilled the
      criteria for ACOS, and 98.4% of them sustained these criteria after 1 year.
      Patients with ACOS were predominantly male (81.6%), with symptomatic mild to
      moderate disease (67%), who were receiving inhaled corticosteroids (63.2%). There
      were no significant differences in baseline characteristics, and only survival
      was worse in patients with non-ACOS COPD after 1 year of follow-up (P < .05).
      CONCLUSIONS: The proposed ACOS criteria are present in 15% of a cohort of
      patients with COPD and these patients show better 1-year prognosis than
      clinically similar patients with COPD with no ACOS criteria. TRIAL REGISTRY:
      ClinicalTrials.gov; No.: NCT01122758; URL: www.clinicaltrials.gov.

PMID- 26291755
TI  - Temperature dependencies of Henry's law constants for different plant
      sesquiterpenes.
AB  - Sesquiterpenes are plant-produced hydrocarbons with important ecological
      functions in plant-to-plant and plant-to-insect communication, but due to their
      high reactivity they can also play a significant role in atmospheric chemistry.
      So far, there is little information of gas/liquid phase partition coefficients
      (Henry's law constants) and their temperature dependencies for sesquiterpenes,
      but this information is needed for quantitative simulation of the release of
      sesquiterpenes from plants and modeling atmospheric reactions in different
      phases. In this study, we estimated Henry's law constants (Hpc) and their
      temperature responses for 12 key plant sesquiterpenes with varying structure
      (aliphatic, mono-, bi- and tricyclic sesquiterpenes). At 25  degrees C, Henry's
      law constants varied 1.4-fold among different sesquiterpenes, and the values were
      within the range previously observed for monocyclic monoterpenes. Hpc of
      sesquiterpenes exhibited a high rate of increase, on average ca. 1.5-fold with a
      10  degrees C increase in temperature (Q10). The values of Q10 varied 1.2-fold
      among different sesquiterpenes. Overall, these data demonstrate moderately high
      variation in Hpc values and Hpc temperature responses among different
      sesquiterpenes. We argue that these variations can importantly alter the emission
      kinetics of sesquiterpenes from plants.

PMID- 26291756
TI  - Kinetic modeling of pH-dependent antimony (V) sorption and transport in iron
      oxide-coated sand.
AB  - Understanding the mechanisms and kinetics controlling the retention and transport
      of antimony (Sb) is prerequisite for evaluating the risk of groundwater
      contamination by the toxic element. In this study, kinetic batch and saturated
      miscible displacement experiments were performed to investigate effects of
      protonation-deprotonation reactions on sorption-desorption and transport of Sb(V)
      in iron oxide-coated sand (IOCS). Results clearly demonstrated that Sb(V)
      sorption was highly nonlinear and time dependent, where both sorption capacity
      and kinetic rates decreased with increasing solution pH. Breakthrough curves
      (BTCs) obtained at different solution pH exhibited that mobility of Sb(V) were
      higher under neutral to alkaline condition than under acidic condition. Because
      of the nonlinear and non-equilibrium nature of Sb(V) retention and transport,
      multi-reaction models (MRM) with equilibrium and kinetic sorption expressions
      were utilized successfully to simulate the experiment data. Equilibrium
      distribution coefficient (Ke) and reversible kinetic retention parameters (k1 and
      k2) of both kinetic sorption and transport experiment showed marked decrease as
      pH increased from 4.0 to 7.5. Surface complexation is suggested as the dominant
      mechanism for the observed pH-dependent phenomena, which need to be incorporated
      into the kinetic models to accurately simulate the reactive transport of Sb(V) in
      vadose zone and aquifers. 

PMID- 26291757
TI  - Quantum chemical study of the photolysis mechanisms of sulfachloropyridazine and
      the influence of selected divalent metal ions.
AB  - Sulfonamides have been found in aquatic environments. Degradation of
      sulfachloropyridazine (SCP) mainly proceeds through direct and indirect
      photolysis in the aquatic environment. However, the mechanisms underlying the
      triplet photolysis of SCP and the influence of metal ions on the photolysis
      mechanism have not yet been fully explained. In this study, we elucidated the
      triplet photolysis mechanisms of SCP and the effects of three selected metal ions
      (Zn(2+), Ca(2+), and Cu(2+)) on the SCP photolysis mechanisms using quantum
      chemical calculation. Optimization of molecular structures and reaction pathways
      analysis of SCP were carried out at the B3LYP/6-31+G(d,p) level of theory. Two
      minimum energy pathways were investigated in the triplet photolysis of SCP. In
      Step 2 of Path-I, the photolysis product of SCP is a sulfur dioxide extrusion
      product, (4-(3-chloro-6-iminopyridazine-1(6H)-yl)aniline). The estimated
      activation energies of Step 2 and Step 3 of Path-I were much higher than in Path
      II. Therefore, Path-II was found as the lowest energy pathway to obtain the SCP
      photoproducts, and Step 2 of Path-II was confirmed as the rate-determining step
      (RDS) in the photolysis mechanism of SCP. For the RDS of Path-II, computations
      with the three metal ions complexes (IM1-Cu(2+), IM1-Ca(2+), and IM1-Zn(2+)) show
      that the metal ions Cu(2+) and Ca(2+) promote triplet-sensitized photolysis of
      SCP by reducing the activation energy of RDS of Path-II, whereas Zn(2+) showed an
      inhibitory effect in photolysis of SCP by increasing the activation energy. 

PMID- 26291758
TI  - Evaluation of concentrations of pharmaceuticals detected in sewage influents in
      Japan by using annual shipping and sales data.
AB  - A year-round monitoring survey of sewage flowing into sewage treatment plants
      located in urban Japan was conducted by targeting seven representative
      pharmaceutical components-atenolol (ATL), ciprofloxacin (CFX), clarithromycin
      (CTM), diclofenac (DCF), diltiazem (DTZ), disopyramide (DSP), and sulpiride (SPR)
      detected in the river environment. For each of these components, two types of
      predicted concentration were estimated on the basis of two types of data (the
      shipping volume and sales volume of each component). The measured concentration
      of each component obtained through the survey and the two types of estimated
      predicted concentration of each component were then compared. The correspondence
      ratio between the predicted concentration estimated from the shipping volume of
      the component and the measured concentration (predicted concentration/measured
      concentration) was, for ATL, 3.1; CFX, 1.4; CTM, 1.4; DCF, 0.2; DTZ, 0.9; DSP,
      11.6; and SPR, 1.1. The correspondence ratio between the predicted concentration
      estimated from the sales volume of the component and the measured concentration
      was, for ATL, 0.5; CFX, 1.1; CTM, 0.8; DCF, 0.1; DTZ, 0.2; DSP, 0.7; and SPR,
      0.8. Although a generally corresponding trend was seen regardless of whether the
      prediction was based on shipping volume or sales volume, the predicted
      concentrations estimated from the shipping volumes of all components expect DSP
      were found, to our knowledge for the first time in Japan, to correspond better
      than those based on sales volumes to the measured concentrations. These findings
      should help to improve the prediction accuracy of concentrations of
      pharmaceutical components in river waters. 

PMID- 26291759
TI  - Source identification, spatio-temporal distribution and ecological risk of
      persistent organic pollutants in sediments from the upper Danube catchment.
AB  - Riverine sediments, collected on a monthly basis during a period of one year,
      from five sites in a mixed land use region of the Czech Republic were analysed
      for chlorinated and brominated persistent organic pollutants (POPs). The region
      is located in the upper catchment of the Danube River. The POPs concentrations
      were as follows: 11-930 pg g(-1) polychlorinated dibenzo-p-dioxins and
      dibenzofurans (PCDDs/Fs), 170-980 pg g(-1) dioxin-like polychlorinated biphenyls
      (dl-PCBs), 34-13,700 pg g(-1) polychlorinated naphthalenes (PCNs), 5.7-29,200 pg
      g(-1) polybrominated diphenylethers (PBDEs) and 0.21-351 ng g(-1)
      hexabromocyclododecanes (HBCDs). Concentrations expressed as toxic equivalents
      (TEQs), for PCDD/F+dl-PCB+PCN (TEQPCDD/F+dl-PCB+PCN) ranged from 0.37 to 19 pg g(
      1). The results revealed a clear spatial separation between sites based on
      concentration and congener profile. There were also some obvious temporal
      patterns of selected POPs, which were related to river flow (seasonality) and
      organic carbon (TOC) of the sediment. Potential sources of POPs include local
      municipalities (flame retardants), some diffuse sources (PCNs and PCDDs/Fs) and
      potential point sources (PBDEs). Risk assessment based on risk quotients (RQ)
      revealed limited to medium ecological risk from PBDEs. TEQPCDD/F+dl-PCB+PCN were
      low relative to other European rivers, hence the risk to aquatic organisms was
      considered to be low. PCNs contributed significantly to overall TEQ in several
      cases.

PMID- 26291760
TI  - Toxic textile dyes accumulate in wild European eel Anguilla anguilla.
AB  - Dyes are used to stain inks, paints, textile, paper, leather and household
      products. They are omnipresent, some are toxic and may threaten our environment,
      especially aquatic ecosystems. The presence of residues of sixteen dyes
      (triarylmethanes, xanthenes, phenothiazines and phenoxazines) and their
      metabolites was analyzed in muscle tissue samples of individual yellow-phased
      European eels (Anguilla anguilla) from 91 locations in Belgian rivers, canals and
      lakes sampled between 2000 and 2009 using ultra performance liquid chromatography
      tandem mass spectrometry. Eel was contaminated by dyes in 77% of the sites.
      Malachite Green, Crystal Violet and Brilliant Green were present in 25-58% of the
      samples. Dye occurrence was related to the distribution of textile and dye
      production industries. This field study is the first large-scale survey to
      document the occurrence of artificial dyes in wildlife. Considering the annual
      amounts of dyes produced worldwide and the unintentional spillage during their
      use, our observations warrant additional research in other parts of the world.
      The presence of these highly toxic dyes in the European eel may form an
      additional threat to this critically endangered species. The contaminated eels
      should be considered as not suitable for consumption. 

PMID- 26291761
TI  - Enantioselective bioaccumulation of hexaconazole and its toxic effects in adult
      zebrafish (Danio rerio).
AB  - Little is known about the bioaccumulation and toxicity of hexaconazole (HEX) in
      spite of the fact that they are indispensable parts for a comprehensive
      assessment of its environmental behavior and toxic effects in organisms of
      freshwater ecosystems. In this study, adult zebrafish were used to study the
      enantioselective bioaccumulation of HEX and its effect endpoints in liver,
      including oxidative stress and the regulation of apoptosis-related gene
      expression. Significant enantioselective bioaccumulation was demonstrated when
      exposed to HEX of 100 and 200 MUg L(-)(1), finding that the (-)-enantiomer tended
      to accumulate in zebrafish more easily than (+)-enantiomer. Activities of
      antioxidant enzymes (SOD, CAT and GPx) and GSH content were all significantly
      decreased when zebrafish were exposed to 50 and 200 MUg L(-1) HEX for 21 d. A
      series of genes of the apoptosis pathway were examined in groups treated with 50
      and 200 MUg L(-)(1) HEX for 21 d using real-time PCR. Significant up-regulation
      of p53, Puma, Apaf-1, caspase-3 and caspase-9 expression and down-regulation of
      Bcl-2/Bax expression ratio were proved. The overall results indicated that
      waterborne HEX was able to produce oxidative stress and induce apoptosis through
      the involvement of caspases in adult zebrafish. The above information will play a
      vital role in the integrated environmental risk assessment of HEX and make its
      toxic mechanism in fish clear.

PMID- 26291762
TI  - Apoptotic neurons induce proliferative responses of progenitor cells in the
      postnatal neocortex.
AB  - Apoptotic cell death is the leading cause of neuronal loss after neonatal brain
      injury. Little is known about the intrinsic capacity of the immature cerebral
      cortex for replacing dead cells. Here we test the hypothesis that neuronal
      apoptosis is able to trigger compensatory proliferation in surrounding cells. In
      order to establish a "pure" apoptotic cell death model and to avoid the
      confounding effects of broken blood-brain barrier and inflammatory reactions, we
      used a diphtheria toxin (DT) and diphtheria toxin receptor (DTR) system to induce
      ablation of layer IV neurons in the rodent somatosensory cortex during the early
      postnatal period. We found that DT-triggered apoptosis is a slowly progressing
      event lasting about for 7 days. While dying cells expressed the morphological
      features of apoptosis, we could not detect immunoreactivity for activated caspase
      3 in these cells. Microglia activation and proliferation represented the earliest
      cellular responses to apoptotic cell death. In addition, we found that induced
      apoptosis triggered a massive proliferation of undifferentiated progenitor cell
      pool including Sox2 as well as NG2 cells. The default differentiation pattern of
      proliferating progenitors appears to be the glial phenotype; we could not find
      evidence for newly generated neurons in response to apoptotic neuronal death.
      These results suggest that mitotically active progenitor populations are
      intrinsically capable to contribute to the repair process of injured cortical
      tissue and may represent a potential target for neuronal replacement strategies.

PMID- 26291763
TI  - Reply to the Editor--LA function is not the only key for best selection of
      candidates for cardiac resynchronization therapy, but LA strain provides valuable
      information!

PMID- 26291764
TI  - Letter to the Editor--Left atrial function may not be an independent predictor
      for CRT response: Implications of ventricular-atrial linking.

PMID- 26291765
TI  - Horizontal DNA transfer from bacteria to eukaryotes and a lesson from
      experimental transfers.
AB  - Horizontal gene transfer (HGT) is widespread among bacteria and plays a key role
      in genome dynamics. HGT is much less common in eukaryotes, but is being reported
      with increasing frequency in eukaryotes. The mechanism as to how eukaryotes
      acquired genes from distantly related organisms remains obscure yet. This paper
      cites examples of bacteria-derived genes found in eukaryotic organisms, and then
      describes experimental DNA transports to eukaryotes by bacterial type 4 secretion
      systems in optimized conditions. The mechanisms of the latter are efficient,
      quite reproducible in vitro and predictable, and thereby would provide insight
      into natural HGT and to the development of new research tools.

PMID- 26291766
TI  - Dynamic stability during running gait termination: Differences in strategies
      between children and adults to control forward momentum.
AB  - Rapid deceleration during running is key for successful participation in most
      childhood activities and sports; this requires modulation of body momentum and
      consequent challenges to postural equilibrium. The purpose of this study was to
      investigate the strategies employed by adults and children to control forward
      momentum and terminate running gait. Sixteen young adults and 15 pre-pubertal
      children completed two tasks as fast as possible: an unobstructed run (RUN) and a
      run and stop (STOP) at a pre-determined location. For STOP, center of mass (COM)
      approach velocity and momentum prior to deceleration and spatiotemporal
      characteristics and COM position during deceleration were compared between
      groups. Position and velocity variables were normalized to height and maximum
      velocity during RUN, respectively. Children used fewer steps with relatively
      longer step length to decelerate over a relatively longer distance and longer
      time than adults. Children approached at higher relative velocity than adults,
      but adults approached with greater momentum. Adults positioned their COM lower
      and more posterior than children throughout deceleration. Our results suggest
      that pre-pubertal children and young adults employ different strategies to
      modulate body momentum, with adults exhibiting mechanics characteristic of a more
      stable strategy. Despite less stable mechanics, children and adults achieved
      similar success. 

PMID- 26291767
TI  - The role of EMT and MET in cancer dissemination.
AB  - Metastatic cancer cells are lethal. Understanding the molecular mechanisms that
      bolster the conversion from benign to malignant progression is key for treating
      these heterogeneous and resistant neoplasms. The epithelial-mesenchymal
      transition (EMT) is a conserved cellular program that alters cell shape, adhesion
      and movement. The shift to a more mesenchymal-like phenotype can promote tumor
      cell intravasation of surrounding blood vessels and emigration to a new organ,
      yet may not be necessary for extravasation or colonization into that environment.
      Lymphatic dissemination, on the other hand, may not require EMT. This review
      presents emerging data on the modes by which tumor cells promote EMT/MET via
      microRNA and prepare the pre-metastatic niche via exosomes. 

PMID- 26291768
TI  - Docetaxel Alone or in Combination With a Therapeutic Cancer Vaccine (PANVAC) in
      Patients With Metastatic Breast Cancer: A Randomized Clinical Trial.
AB  - IMPORTANCE: Previous phase 1 and 2 trials of PANVAC, a poxviral-based cancer
      vaccine, have suggested clinical efficacy in some patients with breast, ovarian,
      and colorectal cancer and have shown evidence of immunologic activity.
      Preclinical data have shown that docetaxel can modify tumor phenotype, making
      tumor cells more amenable to T cell-mediated killing. OBJECTIVE: The goal of this
      study was to determine if the treatment combination of docetaxel and PANVAC
      improves clinical outcomes in patients with metastatic breast cancer compared
      with docetaxel treatment alone. DESIGN, SETTING, AND PARTICIPANTS: Between May
      2006 and February 2012, this open-label, phase 2 randomized clinical trial
      enrolled 48 patients with metastatic breast cancer of all subtypes, without
      limitation on other lines of previous therapy, to receive treatment with either
      docetaxel with PANVAC (arm A) or docetaxel alone (arm B). Final clinical data
      were collected on September 16, 2013. All patients were treated at either the
      National Cancer Institute or the Department of Breast Medical Oncology, MD
      Anderson Cancer Center. MAIN OUTCOMES AND MEASURES: The primary end point was
      progression-free survival (PFS), using a phase 2.5 statistical design, with the
      intent of identifying a trend toward benefit (defined as 1-sided P<=.10) to guide
      a larger trial design. Secondary end points included safety and immunologic
      correlative studies. RESULTS: Forty-eight participants were enrolled: 25 were
      randomized to the combination treatment arm A, and 23 to arm B. No patient
      remained in the study at the time of the final analysis. Patient and tumor
      characteristics were well matched. Analysis of adverse events in both treatment
      arms demonstrated very little difference between the 2 groups. In the combination
      treatment arm (arm A), statistically significant increases were noted in the
      frequency of grades 1 and 2 edema (P=.02, likely related to greater median number
      of docetaxel cycles) and injection-site reactions (P<.001). In the final data
      analysis, median PFS was 7.9 months in arm A vs 3.9 months in arm B (hazard
      ratio, 0.65 [95% CI, 0.34-1.14]; P=.09). CONCLUSIONS AND RELEVANCE: The results
      suggest that the combination of PANVAC with docetaxel in metastatic breast cancer
      may provide a clinical benefit. This study was hypothesis generating and provides
      both rationale and statistical assumptions for a larger definitive randomized
      study. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00179309.

PMID- 26291769
TI  - Word tones cueing morphosyntactic structure: Neuroanatomical substrates and
      activation time-course assessed by EEG and fMRI.
AB  - Previous studies distinguish between right hemisphere-dominant processing of
      prosodic/tonal information and left-hemispheric modulation of grammatical
      information as well as lexical tones. Swedish word accents offer a prime testing
      ground to better understand this division. Although similar to lexical tones,
      word accents are determined by words' morphosyntactic structure, which enables
      listeners to use the tone at the beginning of a word to predict its grammatical
      ending. We recorded electrophysiological and hemodynamic brain responses to words
      where stem tones matched or mismatched inflectional suffixes. Tones produced
      brain potential effects after 136 ms, correlating with subject variability in
      average BOLD in left primary auditory cortex, superior temporal gyrus, and
      inferior frontal gyrus. Invalidly cued suffixes activated the left inferior
      parietal lobe, arguably reflecting increased processing cost of their meaning.
      Thus, interaction of word accent tones with grammatical morphology yielded a
      rapid neural response correlating in subject variability with activations in
      predominantly left-hemispheric brain areas.

PMID- 26291770
TI  - The role of prominence in Spanish sentence comprehension: An ERP study.
AB  - Prominence is the hierarchical relation among arguments that allows us to
      understand 'Who did what to whom' in a sentence. The present study aimed to
      provide evidence about the role of prominence information for the incremental
      interpretation of arguments in Spanish. We investigated the time course of neural
      correlates associated to the comprehension of sentences that require a reversal
      of argument prominence hierarchization. We also studied how the amount of
      available prominence information may affect the incremental build-up of verbal
      expectations. Results of the ERP data revealed that at the disambiguating verb
      region, object-initial sentences (only one argument available) elicited a centro
      parietal negativity with a peak at 400 ms post-onset. Subject-initial sentences
      (two arguments available) yielded a broadly distributed positivity at around 650
      ms. This dissociation suggests that argument interpretation may depend on their
      morphosyntactic features, and also on the amount of prominence information
      available before the verb is encountered.

PMID- 26291771
TI  - Corynebacterium bovis Eye Infections, Washington, USA, 2013.

PMID- 26291772
TI  - Developing from child to adult: Risk factors for poor psychosocial outcome in
      adolescents and young adults with epilepsy.
AB  - INTRODUCTION: Childhood-onset epilepsy during the years of transition to
      adulthood may affect normal social, physical, and mental development, frequently
      leading to psychosocial and health-related problems in the long term. OBJECTIVE:
      This study aimed to describe the main characteristics of patients in transition
      and to identify risk factors for poor psychosocial outcome in adolescents and
      young adults with epilepsy. METHODS: Patients with epilepsy, 15-25years of age,
      who visited the Kempenhaeghe Epilepsy Transition Clinic from March 2012 to
      December 2014 were included (n=138). Predefined risk scores for medical,
      educational/occupational status, and independence/separation/identity were
      obtained, along with individual risk profile scores for poor psychosocial
      outcome. Multivariate linear regression analysis and discriminant analysis were
      used to identify variables associated with an increased risk of poor long-term
      psychosocial outcome. RESULTS: Demographic, epilepsy-related, and psychosocial
      variables associated with a high risk of poor long-term outcome were lower
      intelligence, higher seizure frequency, ongoing seizures, and an unsupportive and
      unstable family environment. Using the aforementioned factors in combination, we
      were able to correctly classify the majority (55.1%) of the patients regarding
      their risk of poor psychosocial outcome. CONCLUSION: Our analysis may allow early
      identification of patients at high risk of prevention, preferably at
      pretransition age. The combination of a chronic refractory epilepsy and an
      unstable family environment constitutes a higher risk of transition problems and
      poor outcome in adulthood. As a consequence, early interventions should be put
      into place to protect youth at risk of poor transition outcome.

PMID- 26291773
TI  - Comparison of short-term effects of midazolam and lorazepam in the intra-amygdala
      kainic acid model of status epilepticus in mice.
AB  - Benzodiazepines remain as the first-line treatment for status epilepticus (SE),
      but debate continues as to the choice and delivery route of pharmacotherapy.
      Lorazepam is currently the preferred anticonvulsant for clinical use, but
      midazolam has become a popular alternative, particularly as it can be given by
      nonintravenous routes. Anticonvulsants are also commonly used to terminate SE in
      animal models. Here, we aimed to compare the efficacy of midazolam with that of
      lorazepam in an experimental model of focal-onset SE. Status epilepticus was
      induced by intra-amygdala microinjection of kainic acid in 8week old C57Bl/6
      mice. Forty minutes later, mice were treated with an intraperitoneal injection of
      either lorazepam or midazolam (8mg/kg). Electroencephalogram (EEG) activity,
      histology, and behavioral tests assessing recovery of function were evaluated and
      compared between groups. Intraperitoneal injection of either lorazepam or
      midazolam resulted in similar patterns of reduced EEG epileptiform activity
      during 1-hour recordings. Damage to the hippocampus and presentation of
      postinsult anxiety-related behavior did not significantly differ between
      treatment groups at 72h. However, return of normal behaviors such as grooming,
      levels of activity, and the evaluation of overall recovery of SE mice were all
      superior at 24h in animals given midazolam compared with lorazepam. Our results
      indicate that midazolam is as effective as lorazepam as an anticonvulsant in this
      model while also providing improved animal recovery after SE. These data suggest
      that midazolam might be considered by researchers as an anticonvulsant in animal
      models of SE, particularly as it appears to satisfy the requirements of refining
      procedures involving experimental animals at early time-points after SE. 

PMID- 26291775
TI  - Etymologia: Surveillance.

PMID- 26291774
TI  - The relevance of neuropsychiatric symptoms and cognitive problems in new-onset
      epilepsy - Current knowledge and understanding.
AB  - Neurobehavioral and cognition problems are highly prevalent in epilepsy, but most
      research studies to date have not adequately addressed the precise nature of the
      relationship between these comorbidities and seizures. To address this complex
      issue and to facilitate collaborative, innovative research in the rising field of
      neurobehavioral comorbidities and cognition disturbances in new-onset epilepsy,
      international epilepsy experts met at the 3rd Halifax International Epilepsy
      Conference & Retreat at White Point, South Shore, Nova Scotia, Canada from
      September 18 to 20, 2014. This Conference Proceedings provides a summary of the
      conference proceedings. Specifically, the following topics are discussed: (i)
      role of comorbidities in epilepsy diagnosis and management, (ii) role of
      antiepileptic medications in understanding the relationship between epilepsy and
      neurobehavioral and cognition problems, and (iii) animal data and diagnostic
      approaches. Evidence to date, though limited, strongly suggests a bidirectional
      relationship between epilepsy and cognitive and psychiatric comorbidities. In
      fact, it is likely that seizures and neurobehavioral problems represent different
      symptoms of a common etiology or network-wide disturbance. As a reflection of
      this shared network, psychiatric comorbidities and/or cognition problems may
      actually precede the seizure occurrence and likely get often missed if not
      screened. 

PMID- 26291776
TI  - Facile Method To Prepare Microcapsules Inspired by Polyphenol Chemistry for
      Efficient Enzyme Immobilization.
AB  - In this study, a method inspired by polyphenol chemistry is developed for the
      facile preparation of microcapsules under mild conditions. Specifically, the
      preparation process includes four steps: formation of the sacrificial template,
      generation of the polyphenol coating on the template surface, cross-linking of
      the polyphenol coating by cationic polymers, and removal of the template. Tannic
      acid (TA) is chosen as a representative polyphenol coating precursor for the
      preparation of microcapsules. The strong interfacial affinity of TA contributes
      to the formation of polyphenol coating through oxidative oligomerization, while
      the high reactivity of TA is in charge of reacting/cross-linking with cationic
      polymer polyethylenimine (PEI) through Schiff base/Michael addition reaction. The
      chemical/topological structures of the resultant microcapsules are simultaneously
      characterized by scanning electron microscopy (SEM), transmission electron
      microscopy (TEM), Fourier Transform infrared spectroscopy (FTIR), X-ray
      photoelectron spectroscopy (XPS), etc. The wall thickness of the microcapsules
      could be tailored from 257+/-20 nm to 486+/-46 nm through changing the TA
      concentration. The microcapsules are then utilized for encapsulating glucose
      oxidase (GOD), and the immobilized enzyme exhibits desired catalytic activity and
      enhanced pH and thermal stabilities. Owing to the structural diversity and
      functional versatility of polyphenols, this study may offer a facile and generic
      method to prepare microcapsules and other kinds of functional porous materials.

PMID- 26291777
TI  - ITPRs/inositol 1,4,5-trisphosphate receptors in autophagy: From enemy to ally.
AB  - ITPRs (inositol 1,4,5-trisphosphate receptors), the main endoplasmic reticulum
      (ER) Ca(2+)-release channels, were originally proposed as suppressors of
      autophagy. Yet, new evidence has accumulated over recent years supporting a
      crucial, stimulatory role for ITPRs in driving the autophagic flux. Here, we
      provide an integrated view on how ITPR-mediated Ca(2+) signaling can have a dual
      impact on autophagy, depending on the characteristics of the spatio-temporal
      Ca(2+) signals, including the existence of ER-mitochondrial and ER-lysosomal
      Ca(2+) signaling microdomains. 

PMID- 26291778
TI  - Regional and Gender Differences and Trends in the Anesthesiologist Workforce.
AB  - BACKGROUND: Concerns have long existed about potential shortages in the
      anesthesiologist workforce. In addition, many changes have occurred in the
      economy, demographics, and the healthcare sector in the last few years, which may
      impact the workforce. The authors documented workforce trends by region of the
      United States and gender, trends that may have implications for the supply and
      demand of anesthesiologists. METHODS: The authors conducted a national survey of
      American Society of Anesthesiologists members (accounting for >80% of all
      practicing anesthesiologists in the United States) in 2007 and repeated it in
      2013. The authors used logistic regression analysis and Seemingly Unrelated
      Regression to test across several indicators under an overarching hypothesis.
      RESULTS: Anesthesiologists in Western states had markedly different patterns of
      practice relative to anesthesiologists in other regions in 2007 and 2013,
      including differences in employer type, the composition of anesthesia teams, and
      the time spent on monitored anesthesia care. The number and proportion of female
      anesthesiologists in the workforce increased between 2007 and 2013, and females
      differed from males in employment arrangements, compensation, and work hours.
      CONCLUSIONS: Regional differences remained stable during this time period
      although the reasons for these differences are speculative. Similarly, how and
      whether the gender difference in work hours and shift to younger
      anesthesiologists during this period will impact workforce needs is uncertain.

PMID- 26291779
TI  - The effect of antenatal magnesium sulfate on left ventricular afterload and
      myocardial function measured using deformation and rotational mechanics imaging.
AB  - OBJECTIVE: Assess the effect of antenatal magnesium sulfate (MgSO4) on left
      ventricular function measured using deformation and rotational mechanics imaging.
      STUDY DESIGN: Infants who received MgSO4 were matched for gestation, birth weight
      and mode of delivery with controls. Echocardiography was carried out on days 1
      and 2 to measure left ventricle longitudinal strain (LV LS), twist, untwist rate,
      ejection fraction (EF), and systemic vascular resistance (SVR). RESULTS: Thirty
      eight infants with a median gestation and birth weight of 27.1 weeks and 923 g
      were included. On day 1, the MgSO4 group (n=19) had a lower SVR and higher LV LS,
      EF, twist and untwist rate than the Control group (n=19) (all P<0.05). There were
      no differences between the groups on day 2. CONCLUSION: Antenatal MgSO4
      administration is associated with a lower SVR and higher myocardial function on
      day 1 in preterm infants <29 weeks gestation.

PMID- 26291780
TI  - The association between umbilical cord abnormalities and the development of non
      reassuring fetal heart rate leading to emergent cesarean deliveries.
AB  - OBJECTIVE: To study the contribution of umbilical cord (UC) abnormalities in
      emergent cesarean deliveries (ECDs) for non-reassuring fetal heart rate (NRFHR)
      and to explore their association with placental histopathology and neonatal
      outcome. STUDY DESIGN: Data from 530 ECDs for NRFHR were reviewed for the
      occurrence of UC abnormalities. Those included the presence of UC entanglements,
      the number and location of loops, true knots and short cord (<50 cm). Multiple UC
      entanglements were defined as ? 2 UC loops. Results were compared with 530
      vaginal deliveries (VD group) matched for maternal age, parity and gestational
      age. Additionally, we compared neonatal outcome and placental histopathology in
      cases of ECDs with a single vs multiple UC entanglements. Neonatal outcome
      consisted of low Apgar score (? 7 at 5 min), cord blood pH ? 7.1 and composite
      neonatal outcome that was defined as one or more of respiratory distress,
      necrotizing enterocolitis, sepsis, transfusion, ventilation, seizure, hypoxic
      ischemic encephalopathy, phototherapy or death. Placental lesions were classified
      as: lesions related to maternal vascular supply, lesions related to fetal
      vascular supply (consistent with fetal thrombo-occlusive disease), and maternal
      and fetal inflammatory responses. RESULTS: UC entanglements, true knots and short
      cords were all more common in the ECD group compared with the VD group, P<0.001,
      P=0.002, P=0.004, respectively. The rate of one loop entanglement did not differ
      between the groups. The rate of multiple UC entanglements was higher in the ECD
      group compared with the VD group, 20.6% vs 6.4%, respectively, P<0.001. ECDs with
      multiple compared with single UC entanglement had higher rate of adverse neonatal
      outcome, P=0.031, and more placental fetal vascular lesions 19.3% vs 8.1%,
      P=0.027, respectively. CONCLUSION: Multiple UC entanglements, true knots and
      short cords were more common in ECDs for NRFHR, suggesting their role in the
      development of fetal placental vascular lesions and adverse neonatal outcome.

PMID- 26291781
TI  - Surfactant foam technology for in situ removal of heavy chlorinated compounds
      DNAPLs.
AB  - The use of surfactant foam for the remediation of a saturated soil contaminated
      with a dense non-aqueous phase liquid (DNAPL) was investigated at bench-scale.
      Despite the presence of the DNAPL, high foam stability was obtained for a mixture
      of cocamidopropyl betaine and dodecylsulfate at 0.05%. Foams were assessed in
      different injection conditions and were compared to commonly used remediation
      methods. Strong foams improved significantly the DNAPL recovery yield, which
      amounted up to 98%, owing to the propagation of a flat foam front, with low
      dissolution (<0.5 g l(-1)) and surfactant consumption (<10 g kg(-1) DNAPL
      recovered). The effects of important parameters (gas to liquid ratio, injection
      velocity, gas nature) and methods for foam production on pressure gradient (?P),
      remediation efficiency and surfactant consumption were investigated. Even for low
      injection velocities (4*10(-4) ms(-1)), capillary numbers were high enough
      (~8*10(-3)) to push the DNAPL efficiently. DNAPL lowered ?P for foam propagation
      because of its destabilising effect. The use of CO2 as gas reduced the ?Ps for
      foam propagation by 35%. ?P were also decreased by 25% for gas to liquid ratios
      lower than 75%, whereas, DNAPL removal remained high. This technology should
      lower spreading risks and treatment costs.

PMID- 26291782
TI  - A diffusivity model for predicting VOC diffusion in porous building materials
      based on fractal theory.
AB  - Most building materials are porous media, and the internal diffusion coefficients
      of such materials have an important influences on the emission characteristics of
      volatile organic compounds (VOCs). The pore structure of porous building
      materials has a significant impact on the diffusion coefficient. However, the
      complex structural characteristics bring great difficulties to the model
      development. The existing prediction models of the diffusion coefficient are
      flawed and need to be improved. Using scanning electron microscope (SEM)
      observations and mercury intrusion porosimetry (MIP) tests of typical porous
      building materials, this study developed a new diffusivity model: the multistage
      series-connection fractal capillary-bundle (MSFC) model. The model considers the
      variable-diameter capillaries formed by macropores connected in series as the
      main mass transfer paths, and the diameter distribution of the capillary bundles
      obeys a fractal power law in the cross section. In addition, the tortuosity of
      the macrocapillary segments with different diameters is obtained by the fractal
      theory. Mesopores serve as the connections between the macrocapillary segments
      rather than as the main mass transfer paths. The theoretical results obtained
      using the MSFC model yielded a highly accurate prediction of the diffusion
      coefficients and were in a good agreement with the VOC concentration measurements
      in the environmental test chamber. 

PMID- 26291783
TI  - Consequences of urban pollution upon skin status. A controlled study in Shanghai
      area.
AB  - OBJECTIVE: After preliminary studies aimed at measuring pertinent biochemical
      parameters, potentially modified in subjects exposed to bad environmental
      conditions, a dedicated study was performed in Shanghai city to evaluate the
      effect of Urban pollution upon human skin and to collect feedback from the
      volunteers under study. METHODS: This study was performed during summer 2008 in
      two different districts of Shanghai, on 159 local residents: 79 subjects from Xu
      Jia Hui (a centre Shanghainese area), more exposed to pollution, and 80 subjects
      from Chong Ming, an agricultural region closely located north of Shanghai (<100
      kms) and less exposed to pollution, according to official data. Biochemical
      parameters were measured on skin, and feedback from volunteers was collected
      through a graduated 'Likert scale' questionnaire under a point scale (strongly
      agree, agree, disagree, strongly disagree and none). RESULTS: The study
      demonstrated significant differences in several biochemical parameters measured
      in Chong Ming area, as compared to Urban area, with an increased ratio of
      squalene/lipids, a lower level of lactic acid and a better cohesion of stratum
      corneum. Both sebum excretion rate and sebum casual levels did not differ between
      the two districts. The volunteer's feedback evidenced a perceived link between
      pollution and their skin problems. CONCLUSION: This study demonstrated a
      significant impact of the pollution upon the skin status, as illustrated by
      changes in superficial biochemical parameters and volunteers' perception.

PMID- 26291784
TI  - Characterization of a Deep-Branching Heterolobosean, Pharyngomonas turkanaensis
      n. sp., Isolated from a Non-Hypersaline Habitat, and Ultrastructural Comparison
      of Cysts and Amoebae Among Pharyngomonas Strains.
AB  - An unusual heterolobosean amoeba, isolate LO, was isolated recently from a sample
      with a salinity of ~40/00, from Lake Turkana in East Africa. 18S rDNA phylogenies
      confirm that isolate LO branches among halophilic amoeboflagellates assigned to
      Pharyngomonas. We examined the ultrastructure of the amoeba and cyst stages of
      isolate LO, as well as the amoebae and cysts of Pharyngomonas kirbyi (isolates
      AS12B and SD1A). The amoebae of all three isolates lacked discrete dictyosomes
      and had discoidal/flattened mitochondrial cristae, but the mitochondria were not
      enrobed by rough endoplasmic reticulum. The cysts of all three isolates showed a
      thick, bipartite cyst wall, and lacked cyst pores. The cysts of isolate LO were
      distinct in that the ectocyst was very loose-fitting, and could contain "crypts".
      No flagellate form of isolate LO has been observed to date, and a salinity-for
      growth experiment showed that isolate LO can grow at 15-1000/00 salinity,
      indicating that it is halotolerant. By contrast, other studied Pharyngomonas
      isolates are amoeboflagellates and true halophiles. Therefore, we propose isolate
      LO as a new species, Pharyngomonas turkanaensis n. sp. It is possible that P.
      turkanaensis descended from halophilic ancestors, and represents a secondary
      reestablishment of a physiology adapted for moderate salinity. 

PMID- 26291785
TI  - Histochemical evidence of beta-chitin in parapodial glandular organs and tubes of
      Spiophanes (Annelida, Sedentaria: Spionidae), and first studies on selected
      Annelida.
AB  - A generic character of the genus Spiophanes (Annelida, Sedentaria: Spionidae) is
      the presence of parapodial glandular organs. Parapodial glandular organs in
      Spiophanes species include secretory cells with cup-shaped microvilli, similar to
      those present in deep-sea inhabiting vestimentiferans and frenulate Siboglinidae.
      These cells are supposed to secrete beta-chitin for tube-building. In this study,
      transverse histological and/or ultrathin sections of parapodial glandular organs
      and tubes of Spiophanes spp. as well as of Glandulospio orestes (Spionidae) and
      Owenia fusiformis (Oweniidae) were examined. Fluorescent markers together with
      confocal laser scanning microscopy, and Raman spectroscopy were used to detect
      chitin in the parapodial glandular organs of Spiophanes and/or in the glands of
      Owenia and Glandulospio. Tubes of these taxa were tested for chitin to elucidate
      the use of it for tube-building. The examinations revealed a distinct labelling
      of the gland contents. Raman spectroscopy documented the presence of beta-chitin
      in both gland types of Spiophanes. The tubes of Spiophanes were found to have a
      grid-like structure that seems to be built with this beta-chitin. Tests of tubes
      of Dipolydora quadrilobata (Spionidae) for chitin were negative. However, the
      results of our study provide strong evidence that Spiophanes species, O.
      fusiformis and probably also G. orestes produce chitin and supposedly use it for
      tube-building. This implies that the production of chitin and its use as a
      constituent part of tube-building is more widespread among polychaetes as yet
      known. The histochemical data presented in this study support previous
      assumptions inferring homology of parapodial glandular organs of Spionidae and
      Siboglinidae based on ultrastructure. Furthermore, transmission electron
      microscopy-based evidence of secretory cells with nail-headed microvilli in O.
      fusiformis suggests homology of parapodial grandular organs across annelids
      including Sipuncula.

PMID- 26291786
TI  - Knotting dynamics of DNA chains of different length confined in nanochannels.
AB  - Langevin dynamics simulations are used to characterize the typical mechanisms
      governing the spontaneous tying, untying and the dynamical evolution of knots in
      coarse-grained models of DNA chains confined in nanochannels. In particular we
      focus on how these mechanisms depend on the chain contour length, Lc, at a fixed
      channel width D = 56 nm corresponding to the onset of the Odijk scaling regime
      where chain backfoldings and hence knots are disfavoured but not suppressed
      altogether. We find that the lifetime of knots grows significantly with Lc, while
      that of unknots varies to a lesser extent. The underlying kinetic mechanisms are
      clarified by analysing the evolution of the knot position along the chain. At the
      considered confinement, in fact, knots are typically tied by local backfoldings
      of the chain termini where they are eventually untied after a stochastic motion
      along the chain. Consequently, the lifetime of unknots is mostly controlled by
      backfoldings events at the chain ends, which is largely independent of Lc. The
      lifetime of knots, instead, increases significantly with Lc because knots can, on
      average, travel farther along the chain before being untied. The observed
      interplay of knots and unknots lifetimes underpins the growth of the equilibrium
      knotting probability of longer and longer chains at fixed channel confinement. 

PMID- 26291787
TI  - Management of Activity in Immune Thrombocytopenia, Fat or Fit?

PMID- 26291788
TI  - UPLC-MS/MS method with automated on-line SPE for the isomer-specific
      quantification of the first-generation anti-HCV protease inhibitors in peripheral
      blood mononuclear cells.
AB  - HCV infection affects over 170 million people worldwide. The current standard for
      treatment of genotype 1 infection is the association of the first generation
      protease inhibitors boceprevir or telaprevir to ribavirin and peginterferon
      alpha. Although the response rate has been improved with these new drugs, some
      pharmacokinetic/pharmacodinamic issues emerged in the past years. To date, some
      analytical methods are available for the quantification of these drugs in plasma;
      however, the real active concentrations of the two drugs are those in
      hepatocytes. Being the withdrawal of hepatocytes too invasive, in this work we
      aimed to develop and validate a chromatographic method coupled with tandem mass
      spectrometry capable of quantifying boceprevir and telaprevir isomers in
      peripheral blood mononuclear cells, used as an "in-vivo" cellular model of
      compartmentalization. The method used an on-line solid phase extraction protocol
      based on the new OSM((r)) platform and was fully validated following FDA
      guidelines. This method showed mean intra- and inter-day inaccuracy and
      imprecision both lower than 15%, high and stable recovery and contained matrix
      effect, with a run time of 6min, comprehensive of SPE extraction. The method was
      then applied on 35 real samples from patients treated with boceprevir or
      telaprevir, with good analytical performances, thus assessing its eligibility for
      a possible future routine use. Peculiar pharmacokinetic data have been observed,
      suggesting the usefulness of investigating intracellular pharmacokinetics of
      these drugs. Further studies will be required to test the correlation of
      intracellular concentrations with effectiveness and toxicity of triple therapy.

PMID- 26291789
TI  - Determination and quantification of 2'-O-fucosyllactose and 3-O-fucosyllactose in
      human milk by GC-MS as O-trimethylsilyl-oxime derivatives.
AB  - Human milk oligosaccharides possess various biological functions by protecting
      the infant from several bacterial and viral infections, modulating the immune
      system, serving as prebiotics and also contributing to the brain development.
      Hence, huge effort is underway by manufacturers to produce infant formulas
      enriched with human milk oligosaccharides which could mimic its diverse
      biological role the most. For this purpose, quantification of the natural
      oligosaccharide composition of the human milk is a key task. This study reports a
      fit for purpose GC-MS method for the quantification of the TMS ether oxime
      derivatives of 2'-O-fucosyllactose and 3-O-fucosyllactose, the two most abundant
      trisaccharides in human milk. The EI fragmentation pattern of the linkage isomers
      is discussed in details, focusing also on specific fragment ions. The GC-MS
      method with external standard calibration was applied for the monitoring of
      concentration changes of the trisaccharides throughout the first week of
      lactation in human milks samples collected from two volunteers. The results
      showed high concentration of both 2'-FL (4525-6266MUg/mL in donor A and 2694
      3551MUg/mL in donor B) and 3-FL (271-441MUg/mL in donor A and 99-208MUg/mL in
      donor B), while no significant change has been observed throughout the one-week
      lactation period. The presented GC-MS method can serve as a quality control
      technique for the infant formulas and also offers an alternative to existing
      chromatographic methods to investigate HMOs in milk samples.

PMID- 26291790
TI  - Simultaneous determination of multiple androgens in mice organs with liquid
      chromatography tandem mass spectrometry.
AB  - Prostate cancer (PCa) is the most commonly diagnosed cancer in men worldwide. It
      is essentially dependent on potent androgens, such as testosterone (T) and
      dihydrotestosterone (DHT). The precursors of T and DHT, which includes
      androstenedione (A4) and dihydroepiandrosterone (DHEA), and also the metabolites
      of DHT, 5alpha-androstane-3alpha,17beta-diol (3alpha-Diol) and 5alpha-androstane
      3beta,17beta-diol (3beta-Diol) are able to affect the development of PCa.
      Therefore, it is important to simultaneously determine all these key androgens.
      This study aims to develop and validate an LC-MS/MS quantification method to
      simultaneously detect and quantify the six related androgens, including T, DHT,
      A4, DHEA, 3alpha-Diol, and 3beta-Diol in limited sample volume. The sample
      preparation involved liquid extraction with methyl tert-butyl ether (MTBE),
      following by chemical derivatisation with hydroxylamine. The limits of
      quantitation for T, DHT, A4, and DHEA were 0.05nM and 3alpha-Diol and 3beta-Diol
      were 0.5nM with S/N ratio of at least 5:1 by using 100MUL samples.

PMID- 26291792
TI  - Pharmacovigilance in China: issues of concern identified through an analysis of
      the Chinese Adverse Drug Reaction Information Bulletin 2001 to 2014.
AB  - WHAT IS KNOWN AND OBJECTIVE: The Adverse Drug Reaction Information Bulletin
      (ADRIB), issued by China Food and Drug Administration (CFDA), is a major source
      of information on drugs causing safety concerns in China. As the publication is
      only published in Chinese, we undertook an analysis of the reports in the ADRIB
      since its first publication in 2001 to give international readers a better
      appreciation of the pharmacovigilance issues addressed. METHODS: Every issue of
      the ADRIB was scrutinized, and the issues addressed as well as the drugs involved
      are summarized and discussed. RESULTS AND DISCUSSION: From 2001 to 2014, 109
      items of ADR information have been reported. The antimicrobial agents were most
      often the subject of discussion. There were 28 traditional Chinese medicines
      (TCMs) discussed. Among the ADRs addressed, the adverse reactions of the skin and
      its appendages were most frequent. About two-fifths of the ADRs arose from the
      inherent properties of the active substance, and a majority of the ADRs were
      caused by off-label use, irrational drug combinations and misuse in special
      populations. WHAT IS NEW AND CONCLUSION: Many of the pharmacovigilance issues
      addressed were similar to those considered by Western Drug Regulatory Agencies.
      The pharmacovigilance issues relating to Chinese traditional medicines are less
      well addressed internationally, and these would be of particular value as the use
      of such medicines increases in the West.

PMID- 26291791
TI  - National survey and community advisory board development for a bipolar disorder
      biobank.
AB  - OBJECTIVES: The aim of the present study was to engage a national advocacy group
      and local stakeholders for guidance in developing a bipolar disorder biobank
      through a web-based survey and a community advisory board. METHODS: The
      Depression and Bipolar Support Alliance and the Mayo Clinic Bipolar Biobank
      conducted a national web-based survey inquiring about interest in participating
      in a biobank (i.e., giving DNA and clinical information). A community advisory
      board was convened to guide establishment of the biobank and identify key
      deliverables from the research project and for the community. RESULTS: Among 385
      survey respondents, funding source (87%), professional opinion (76%), mental
      health consumer opinion (79%), and return of research results (91%) were believed
      to be important for considering study participation. Significantly more patients
      were willing to participate in a biobank managed by a university or clinic
      (78.2%) than one managed by government (63.4%) or industry (58.2%; both p <
      0.001). The nine-member community advisory board expressed interest in research
      to help predict the likelihood of bipolar disorder developing in a child of an
      affected parent and which medications to avoid. The advisory board endorsed the
      use of a comprehension questionnaire to evaluate participants' understanding of
      the study (e.g., longevity of DNA specimens, right to remove samples, accessing
      medical records) as a means to strengthen the informed consent process.
      CONCLUSIONS: These national survey and community advisory data support the merit
      of establishing a biobank to enable studies of disease risk, provided that health
      records and research results are adequately protected. The goals of earlier
      diagnosis and individualized treatment of bipolar disorder were endorsed.

PMID- 26291793
TI  - Evidence for a Common Origin of Blacksmiths and Cultivators in the Ethiopian Ari
      within the Last 4500 Years: Lessons for Clustering-Based Inference.
AB  - The Ari peoples of Ethiopia are comprised of different occupational groups that
      can be distinguished genetically, with Ari Cultivators and the socially
      marginalised Ari Blacksmiths recently shown to have a similar level of genetic
      differentiation between them (FST ~ 0.023 - 0.04) as that observed among multiple
      ethnic groups sampled throughout Ethiopia. Anthropologists have proposed two
      competing theories to explain the origins of the Ari Blacksmiths as (i) remnants
      of a population that inhabited Ethiopia prior to the arrival of agriculturists
      (e.g. Cultivators), or (ii) relatively recently related to the Cultivators but
      presently marginalized in the community due to their trade. Two recent studies by
      different groups analysed genome-wide DNA from samples of Ari Blacksmiths and
      Cultivators and suggested that genetic patterns between the two groups were more
      consistent with model (i) and subsequent assimilation of the indigenous peoples
      into the expanding agriculturalist community. We analysed the same samples using
      approaches designed to attenuate signals of genetic differentiation that are
      attributable to allelic drift within a population. By doing so, we provide
      evidence that the genetic differences between Ari Blacksmiths and Cultivators can
      be entirely explained by bottleneck effects consistent with hypothesis (ii). This
      finding serves as both a cautionary tale about interpreting results from
      unsupervised clustering algorithms, and suggests that social constructions are
      contributing directly to genetic differentiation over a relatively short time
      period among previously genetically similar groups. 

PMID- 26291794
TI  - Changes in Metabolic Hormones in Malaysian Young Adults following Helicobacter
      pylori Eradication.
AB  - BACKGROUND: More than half of the world's adults carry Helicobacter pylori. The
      eradication of H. pylori may affect the regulation of human metabolic hormones.
      The aim of this study was to evaluate the effect of H. pylori eradication on meal
      associated changes in appetite-controlled insulinotropic and digestive hormones,
      and to assess post-eradication changes in body mass index as part of a currently
      on-going multicentre ESSAY (Eradication Study in Stable Adults/Youths) study.
      METHODS: We enrolled 29 H. pylori-positive young adult (18-30 year-old) volunteer
      subjects to evaluate the effect of H. pylori eradication on meal-associated
      changes on eight gastrointestinal hormones, using a multiplex bead assay. Changes
      in body mass index and anthropometric measurements were recorded, pre- and post
      eradication therapy. RESULTS: Pre-prandial active amylin, total peptide YY (PYY)
      and pancreatic polypeptide (PP) levels were significantly elevated 12 months post
      eradication compared with baseline (n = 18; Wilcoxon's signed rank test, p<0.05).
      Four of the post-prandial gut metabolic hormones levels (GLP-1, total PYY, active
      amylin, PP) were significantly higher 12 months post-eradication compared to
      baseline (n = 18; p<0.05). Following H. pylori eradication, the BMI and
      anthropometric values did not significantly change. CONCLUSIONS: Our study
      indicates that H. pylori eradication was associated with long-term disturbance in
      three hormones (active amylin, PP and total PYY) both pre- and post-prandially
      and one hormone (GLP-1) post-prandially. Longer post-eradication monitoring is
      needed to investigate the long-term impact of the observed hormonal changes on
      metabolic homeostasis.

PMID- 26291795
TI  - Hyperprolactinemia: pathophysiology and therapeutic approach.
AB  - Prolactin (PRL) is a hormone, mainly secreted by lactotroph cells of the anterior
      pituitary gland. Recent studies have shown it may also be produced by many
      extrapituitary cells. Its well-recognized PRL plays an important role in
      lactation during pregnancy, but it is involved in other biological functions such
      as angiogenesis, immunoregulation and osmoregulation. Hyperprolactinemia is a
      typical condition producing reproductive dysfunction in both sexes, resulting in
      hypogonadism, infertility and galactorrhea. It may be also asymptomatic.
      Lactotroph adenomas (prolactinoma) is one of the most common cause of PRL excess,
      representing approximately 40% of all pituitary tumors. Several other conditions
      should be excluded before a clear diagnosis of hyperprolactinemia is made.
      Hyperprolactinemia may be secondary to pharmacological or pathological
      interruption of hypothalamic-pituitary dopaminergic pathways or idiopathic.
      Stress, renal failure or hypothyroidism are other frequent conditions to exclude
      in patients with hyperprolactinemia. We will review biochemical characteristics
      and physiological functions of that hormone. Clinical and pharmacological
      approach to hyperprolactinemia will also be discussed. 

PMID- 26291796
TI  - Evaluation of circulating betatrophin levels in gestational diabetes mellitus.
AB  - Experimental data indicate that betatrophin plays a significant role in the
      regulation of lipid metabolism and glucose homeostasis. In recent years,
      considerable attention has focused on the relationship between betatrophin and
      diabetes mellitus in humans. This case-control study included 45 women diagnosed
      with gestational diabetes mellitus (GDM) and 45 pregnant healthy controls. The
      groups were matched for maternal and gestational age and body mass index. Serum
      betatrophin levels were significantly higher in women with GDM (median = 635.8
      ng/L; range: 290-1841.6 ng/L) compared to control subjects (median = 320.1 ng/L;
      range: 94.6-936.8 ng/L; p = 0.001). No significant correlations were observed
      between serum betatrophin levels and clinical or biochemical parameters in the
      control group. However, in the GDM group, serum betatrophin levels were
      positively correlated with weight gain during pregnancy (r = 0.304, p = 0.042),
      systolic blood pressure (r = 0.394, p = 0.007), fasting insulin level (r = 0.348,
      p = 0.019), and homeostatic model assessment insulin resistance (HOMA-IR; r =
      0.311, p = 0.038). Multivariate stepwise linear regression analysis revealed that
      fasting insulin levels (beta = 0.342, p = 0.022) and HOMA-IR (beta = 0.312, p =
      0.037) were independently associated with serum betatrophin levels. 

PMID- 26291797
TI  - The adjuvant effect of metformin and N-acetylcysteine to clomiphene citrate in
      induction of ovulation in patients with Polycystic Ovary Syndrome.
AB  - OBJECTIVES: To assess the adjuvant effect of metformin and N-acetylcysteine (NAC)
      to clomiphene citrate (CC) in induction of ovulation in Polycystic Ovary Syndrome
      (PCOS) patients. STUDY DESIGN: 120 women with PCOS were randomly divided into
      three equal groups: group I received CC only, group II received CC plus NAC and
      group III received CC plus metformin. RESULTS: There was a significant difference
      between group II and other two groups regarding average number of ovulatory
      follicles >18 mm (2.25 versus 1.75 and 1.89, respectively), but no significant
      difference between the three study groups regarding number of intermediate
      follicles 14-18 mm (4, 10 and 4, respectively). There was no significant
      difference between the three study groups regarding occurrence and laterality of
      ovulation, pregnancy rate per cycle but a significant difference between group II
      and other two groups regarding pregnancy rate per patient (20% versus 10% and
      10%, respectively, p value 0.05). There was a highly statistically significant
      difference between group II and other two groups regarding peak endometrial
      thickness (7.3 +/- 1.1 versus 5.4 +/- 0.6 and 5.3 +/- 0.6, respectively).
      CONCLUSIONS: NAC as an adjuvant to CC for induction of ovulation improves
      ovulation and pregnancy rates in PCOS patients with beneficial impacts on
      endometrial thickness.

PMID- 26291799
TI  - Effect of local estrogen therapy (LET) on urinary and sexual symptoms in
      premenopausal women with interstitial cystitis/bladder pain syndrome (IC/BPS).
AB  - The association between vulvodynia and interstitial cystitis/bladder pain
      syndrome (IC/BPS), a chronic, debilitating disease of unknown etiology, may
      involve sex hormone-dependent mechanisms regulating vulvo-vaginal health. We
      aimed to prospectively investigate the effects of 12 weeks of local estrogen
      therapy (LET) on urinary/bladder and sexual symptoms in premenopausal women with
      IC/BPS. Thirty-four women (mean age: 36.1 +/- 8.4) diagnosed with IC/BPS were
      treated vulvo-vaginally three-times/week with estriol 0.5 mg cream and tested by
      validated questionnaires (ICSI/ICPI, pain urgency frequency [PUF], female sexual
      function index [FSFI]) and by cotton swab testing, vaginal health index (VHI) and
      maturation index (MI) before and after treatment. Vulvodynia was present in 94.1%
      of IC/BPS women. A significant positive effect of LET was evident on urinary and
      sexual function (p < 0.001, for both) following 12 weeks, as well as an
      improvement of the VHI (p < 0.001) and the MI (p < 0.04). The results of this
      open study indicate that 12 weeks of local estriol cream at vaginal and
      vestibular level may ameliorate urinary/bladder pain symptoms, as well as may
      improve domains of sexual function. The association between vulvar pain and
      bladder pain could, therefore, be related to a vaginal environment carrying signs
      of hypoestrogenism, but further studies are needed to clarify this issue. 

PMID- 26291798
TI  - Are FSHR polymorphisms risk factors to premature ovarian insufficiency?
AB  - Premature ovarian insufficiency (POI) is an ovarian dysfunction characterized by
      increased FSH levels and amenorrhea before 40 years old. In recent years, the
      search for genetic causes of POI intensified and studies have been published
      relating the presence of mutations and polymorphisms in genes associated with
      development, recruitment and oocyte atresia. The aim of this study was to
      evaluate the presence of FSHR polymorphisms in our population and contribute with
      the elucidation of POI etiology. To achieve it, we have studied 100 patients with
      POI (G1), 60 patients with border line levels of FSH (G2) and 123 controls with
      regular menopause onset. Cytogenetic analysis of patients' samples and genotyping
      of Asn680Ser and Ala307Thr polymorphisms were performed in cases and controls.
      Cytogenetic analysis showed that 92% of G1 patients had normal karyotype, 4%
      presented polymorphic variants, 3% presented mosaic karyotype involving X
      chromosome. In G2, 91.6% had normal karyotype results, 3.2% displayed polymorphic
      variants, and 3.3% presented a mosaic karyotype involving X chromosome.
      Statistical comparison showed that the polymorphic allele of Ala307Thr
      polymorphism is more frequent in patients than in controls (G1: p < 0.001 and G2:
      p = 0.0259). This association has not been previously reported. We concluded that
      Ala307Thr polymorphism in FSHR can be potentially associated to POI development
      and can be considered as a screening marker in patients with ovarian failure
      signals. 

PMID- 26291800
TI  - Levetiracetam ameliorates ovarian function in streptozotocin-induced diabetic
      rats.
AB  - Diabetes mellitus can adversely affect gonadal function. In the present study, we
      aimed to investigate the protective effects and mechanism of action of
      levetiracetam (LEV) on the ovaries in a streptozotocin (STZ)-induced diabetes
      model in rats. Twenty-one adult female rats were assigned to three groups as
      control, diabetes group treated with 1 mL/kg/d saline (STZ + SP) and diabetes
      group treated with 600 mg/kg/d LEV (STZ + LEV). Following 4 weeks treatment,
      blood samples were collected for biochemical analysis and ovariectomy was
      performed for histopathological examination. Plasma anti-Mullerian hormone (AMH),
      glutathione and total anti-oxidant capacity values were significantly lower
      whereas lipid peroxides and transforming growth factor-beta (TGF-beta) values
      were significantly higher in STZ + SP group compared to control. LEV treatment
      successfully decreased lipid peroxidation and TGF-beta levels, and also increased
      anti-oxidant parameters and AMH levels in diabetic rats. Saline-treated rats
      significantly displayed ovarian degeneration and decreased counts of follicles.
      However, treatment of diabetic rats with LEV effectively prevented the
      degenerative changes and follicle loss. Also, LEV suppressed ovarian nuclear
      factor-kappa B (NF-kB) immunoexpression in diabetic rats. Taken together, we
      propose that LEV can ameliorate the adverse effects of diabetes on ovarian
      function via decreasing NF-kB expression and oxidative stress and increasing anti
      oxidant status in rats. 

PMID- 26291801
TI  - Outcomes of treatment with cyclic administration of dienogest after ovarian
      endometriotic cystectomy.
AB  - To evaluate the outcomes of patients treated with cyclic administration of
      dienogest after ovarian endometriotic cystectomy, following the completion of
      treatment. We retrospectively evaluated 26 patients treated with dienogest (2
      mg/day) after cystectomy (revised American Society for Reproductive Medicine [r
      ASRM] stage III-IV) in a pilot study. Dienogest was administered cyclically, for
      a total of six cycles, each comprising three weeks on and one week off. Outcomes
      of interest included severity of menstrual pain and recurrence of cysts at
      baseline, during the immediate post-treatment period and at the final outpatient
      follow-up. The mean outpatient follow-up period was 45.0 months. The visual
      analog scale score for menstrual pain following 6 cycles of dienogest treatment
      was significantly lower than that at baseline; it remained low at the final
      follow-up. The recurrence rates of cysts were 4% and 21% at 24 and 48 months
      after the completion of dienogest treatment, respectively. Six patients with
      recurrent disease were all classified as having r-ASRM stage IV. Our results
      suggest that cyclic dienogest for six months after cystectomy could relieve
      menstrual pain and reduce the recurrence of cysts, for approximately four years.
      The necessary treatment period for patients with r-ASRM stage IV disease requires
      further study. 

PMID- 26291802
TI  - Endogenous thrombin potential in polycystic ovary syndrome: the association to
      body mass index, insulin resistance, and inflammation.
AB  - OBJECTIVES: The objective of this study is to investigate plasma endogenous
      thrombin generation in four different phenotypes of polycystic ovary syndrome
      (PCOS) defined by Body Mass Index (BMI) and insulin resistance (IR). PCOS is
      diagnosed according to the Rotterdam criteria. DESIGN: Multicenter cross
      sectional study. SETTING: Two major University Hospitals in the Capital region of
      Denmark. PATIENTS: Hundred forty-eight European women with PCOS were
      consecutively recruited during April 2010-February 2012. Clinical examination,
      blood sampling, and DEXA scan were performed. MAIN OUTCOME MEASURES: Endogenous
      thrombin potential (ETP). RESULTS: PCOS women with phenotype BMI > 25 + IR have
      increased potential of thrombin generation. ETP is associated with total body fat
      mass, IR, and CRP. CONCLUSIONS: Obese and insulin resistant women with PCOS have
      elevated level of ETP corresponding to increased risk of CVD. ETP is related to
      well-known CVD risk factors in PCOS but not in general to the Rotterdam criteria.

PMID- 26291803
TI  - Papillophlebitis associated with the use of oral contraceptive: a case report.
AB  - We present a 20-year-old female patient with papillophlebitis in the right eye.
      Minimal expansion of the blind spot and nasal peripheral defects in the right eye
      visual field were detected. The patient was using ethinyl estradiol-cyproterone
      acetate for ovarian cyst and menstrual irregularity. An improvement in the
      patient's visual field began within a week after cessation of ethinyl estradiol
      cyproterone acetate. Ophthalmoscopic findings resolved completely in the sixth
      week. This situation suggests that female sex hormones or thromboembolic process
      caused by them may be responsible for the pathogenesis of papillophlebitis. But
      the exact mechanism in the pathogenesis of papillophlebitis is still
      controversial. 

PMID- 26291804
TI  - 1-h Postprandial glucose level is related to the serum anti-Mullerian hormone
      level in women with polycystic ovary syndrome.
AB  - The aim of this study was to evaluate the relationship between the serum anti
      Mullerian hormone (AMH) level and parameters related to insulin resistance in
      Korean women with polycystic ovary syndrome (PCOS). A total of 95 Korean women
      aged 18-33 years who were newly diagnosed with PCOS according to the Rotterdam
      Consensus at a university hospital were included in this study. Blood samples
      were collected from all participants during the early follicular phase using
      tubes without anticoagulants after an overnight fasting to determine the serum
      AMH level and other biochemical parameters, and then a standard 2-h 75-g oral
      glucose tolerance test (OGTT) was performed for all participants. All patients
      with PCOS were divided into two groups based on the serum AMH level: group 1 (AMH
      < 10.0 ng/ml) and group 2 (AMH >= 10.0 ng/ml). The clinical variables were not
      significantly different between the two groups. The mean postprandial glucose
      level at 1 h (PPG1) in group 1 (111.70 +/- 4.9 mg/dl) was significantly lower
      than that in group 2 (136.76 +/- 9.86 mg/dl). No significant differences between
      the two groups were found in the other insulin resistance-related parameters. In
      conclusion, the serum AMH level may be related to PPG1 in women with PCOS. 

PMID- 26291805
TI  - Ovarian stimulation for oocyte cryopreservation for prevention of age-related
      fertility loss: one in five is a low responder.
AB  - Oocyte cryopreservation for age-related fertility loss is gaining interest
      considering the tendency to postpone motherhood in many societies. Little is
      currently known about the actual efficiency of this approach. We aimed to explore
      ovarian response of presumably fertile women undergoing in vitro fertilization
      for this indication. A total of 105 women underwent 151 stimulation cycles at
      mean age 37.7 +/- 2.4. None had known infertility. Mean daily starting FSH dose
      was 371 +/- 110 (225-600). Mean number of mature oocytes cryopreserved at the
      first completed cycle was 9.7 +/- 7.5 (0-43). However, 21% of started cycles were
      either cancelled before egg retrieval or resulted in 0-3 mature oocytes
      retrieved. Therefore, women considering oocyte cryopreservation for prevention of
      age-related fertility decline should be encouraged to perform this procedure at
      younger age than, preferably before 35. 

PMID- 26291806
TI  - Evaluation of the effects of fulvestrant and micronized progesterone on the post
      operative adhesion formation and ovarian reserve in rat model with
      immunohistochemical and biochemical analysis.
AB  - OBJECTIVE: To evaluate the effects of fulvestrant and micronized progesterone on
      post-operative adhesion formation and ovarian reserve in a rat uterine horn
      adhesion. METHODS: In this prospective randomized controlled trial, 32 female
      Wistar albino rats were randomly divided into four groups including control group
      (Group 1), the control adhesion group (Group 2), 1 mg/kg daily intramuscular
      fulvestrant received group (Group 3) and 1 mg/kg daily oral micronized
      progesterone received group (Group 4). The extent and severity of adhesions were
      scored and samples were taken from adhesion areas to investigate the grades of
      adhesions according to the immunohistochemical scoring system. Ovarian reserves
      were measured with anti-Mullerian hormone (AMH) and histological ovarian
      follicles count. RESULTS: The extent, severity and total adhesion scores were
      reduced in all treatment groups compared to control adhesion group (Group 2).
      Similarly, immunohistochemical adhesion scores were lower in the treatment
      groups. AMH and follicle count were significantly found lower in adhesion groups
      compared with control group. However, treatment groups were found to have higher
      ovarian reserve compared to control adhesion group (Group 2). CONCLUSIONS:
      Fulvestrant and micronized progesterone were found to reduce post-operative
      adhesion formations and have decreased detrimental effects of adhesion formation
      on ovarian reserve.

PMID- 26291807
TI  - A possible association between sports and isolated fallopian tube torsion in
      children and adolescent females.
AB  - Isolated fallopian tube torsion (IFTT) is a rare occurrence characterized by the
      rotation of the fallopian tube on its own axis, without twisting the ipsilateral
      ovary. Pre-operative diagnosis is difficult due to the lack of specific clinical
      symptoms and radiological signs. The etiology is to date unknown and only some
      pre-disposing factors have been reported. The history, clinical presentation,
      laboratory findings and surgical treatment of five patients aged 12-16 with IFTT
      were evaluated. All patients came to be examined for worsening abdominal pain,
      nausea or vomiting. 75% of them practiced sports involving sudden changes in body
      position. They all underwent blood tests, ultrasound and Magnetic Resonance and
      then laparoscopy for the persistence of acute symptoms. Laparoscopic
      salpingectomy was performed in three patients. Another two needed a conversion to
      open salpingectomy due to the presence of pelvic adhesions. During the follow-up
      period, every girl was fine. The cause of IFTT is undetermined. In this series, a
      close association between IFTT and sports causing rapid body movements was found.
      The possibility of IFTT should be considered in the differential diagnosis of
      acute abdominal pain in children or adolescent females, especially if they
      practice sports. 

PMID- 26291808
TI  - Discordant Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome in identical twins - a
      case report and implications for reproduction in MRKH women.
AB  - Infertility has previously been considered as an inevitable consequence of Mayer
      Rokitansky-Kuster-Hauser (MRKH) syndrome. With modern assisted reproductive
      technology (ART) techniques becoming increasingly accessible, MRKH women have the
      opportunity for their own genetic offspring. The availability of such technology,
      however, increases the importance of understanding the aetiology of this complex
      condition. The literature debating the relevance of genetic versus post-zygotic
      events in the aetiology of MRKH syndrome is reviewed in the context of this
      report of monozygotic twins discordant for MRKH syndrome. 

PMID- 26291809
TI  - How much weight are women gaining during pregnancy? An Italian cohort study.
AB  - INTRODUCTION: The 2009 Institute of Medicine (IOM) guidelines define adequate
      gestational weight gain (GWG) in the attempt to prevent maternal and neonatal
      adverse outcomes. The aim of this study was to assess whether the IOM guidelines
      are met in pregnant women with different pre-gestational body mass index (BMI).
      METHODS: The study included 230 pregnant women recruited at the University
      Hospital of Pisa (Italy) at their screening visit (24-28 weeks of gestation) for
      gestational diabetes (GDM). GWG was determined at screening time and before
      delivery to be compared with GWG recommended by IOM for each pre-pregnancy BMI
      category. RESULTS: A total of 48% of women had a GWG exceeding IOM
      recommendations. The prevalence of GWG excess was higher in over-weight (OW,
      63.2%) and obese (OB, 63.8%) women as compared to normal-weight (NW, 27.7%; p <
      0.0001) women. The upper limit of the recommended IOM weight gain range was
      already exceeded at screening time in 15.5% of women. The percentage increased
      27% and 18% in OW and OB, respectively, compared with 1.5% in NW (p < 0.001).
      CONCLUSION: About half of pregnant women had a GWG greater than the IOM
      recommended. GWG excess is particularly evident in OW and OB women.

PMID- 26291810
TI  - Assessment of obstructive sleep apnea-hypopnea syndrome risk at the end of
      pregnancy using the Berlin Questionnaire.
AB  - OBJECTIVE: To assess the risk of obstructive sleep apnea-hypopnea syndrome
      (OSAHS) and related factors at the end of pregnancy using the Berlin
      questionnaire. METHODS: A total of 367 women at the end of pregnancy (median
      gestational age 39 weeks) were interviewed with the Berlin questionnaire and a
      general survey containing maternal socio-demographic and anthropometric
      information. Neonatal outcome data were also assessed. RESULTS: Median age for
      the whole sample was 31 years. According to the Berlin questionnaire, 39.8% were
      positive for high risk of OSAHS. Upon bivariate analysis, higher risk of OSAHS
      was significantly related to church attendance, and higher pre-pregnancy body
      mass index (BMI), current BMI, weight, neck and arm circumference and systolic
      blood pressure at survey. Logistic regression analysis found that higher maternal
      pre-pregnancy BMI (OR 2.71 95% CI 1.84-4.00, p < 0.0001) and higher maternal
      weight at survey (OR 3.02, 95% CI 1.78-5.17, p < 0.0001) were significantly
      related to a higher risk of OSAHS. CONCLUSION: The risk of OSAHS is relatively
      high at the end of pregnancy and related to a higher pre-pregnancy BMI and higher
      maternal weight at survey. Further studies are needed to confirm our results with
      a diagnostic tool, such as polysomnography or another similar yet less
      complicated to carry out procedure.

PMID- 26291811
TI  - Effect of oral contraceptives containing estradiol and nomegestrol acetate or
      ethinyl-estradiol and chlormadinone acetate on primary dysmenorrhea.
AB  - OBJECTIVE: To study the three cycles effect on primary dysmenorrhea of the
      monophasic 24/4 estradiol/nomegestrol acetate (E2/NOMAC) and of the 21/7 ethinyl
      estradiol/chlormadinone acetate (EE/CMA) oral contraceptive. The tolerability and
      the effect of both preparations on metabolism and health-related quality of life
      were also evaluated. DESIGN: Prospective observational cohort study. SETTING:
      Tertiary gynecologic center for pelvic pain. PATIENTS: Subjects with primary
      dysmenorrhea requiring an oral contraceptive, who spontaneously selected either
      E2/NOMAC (n = 20) or EE/CMA (n = 20). MAIN OUTCOME MEASURES: Visual Analogue
      Scale (VAS) score for dysmenorrhea, Short Form-36 questionnaire for health
      related quality of life, lipoproteins and days of menstrual bleeding (withdrawal
      bleeding during oral contraceptive). RESULTS: Mean age and body mass index (BMI)
      were similar between the two groups. The final analysis was performed on 34
      women, 15 in E2/NOMAC and 19 in EE/CMA group. Compliance with treatment was
      significantly higher with EE/CMA (100%) than E2/NOMAC (75%) (p = 0.02). Both
      treatments significantly (p < 0.0001) reduced VAS of primary dysmenorrhea,
      similarly (E2/NOMAC by a mean of 74.7%, EE/CMA by a mean of 78.4%; p = 0.973).
      Only E2/NOMAC significantly increased SF-36 score (p = 0.001), both in physical
      (p = 0.001) and mental domains (p = 0.004). The mean number of days of menstrual
      bleeding was significantly reduced in E2/NOMAC group (from 4.86 +/- 1.20 d to
      2.64 +/- 1.59 d, p = 0.0005 versus baseline, p = 0.007 versus EE/CMA group). BMI
      did not vary in either group. E2/NOMAC did not change lipoproteins and
      apoproteins while EE/CMA increased total cholesterol (p = 0.0114), HDL
      cholesterol (p = 0.0008), triglycerides (p = 0.002), apoprotein-A1 (Apo-A1; p =
      0.0006) and apopoprotein-B (Apo-B; p = 0.008), decreasing LDL/HDL ratio (p =
      0.024). CONCLUSIONS: Both oral contraceptives reduced similarly primary
      dysmenorrhea, with E2/NOMAC also reducing withdrawal bleedings and being neutral
      on lipid metabolism.

PMID- 26291812
TI  - Evidence of the activation of unfolded protein response in granulosa and cumulus
      cells during follicular growth and maturation.
AB  - The objective of the present study is to investigate whether unfolded protein
      response (UPR), activated by endoplasmic reticulum (ER) stress, in granulosa
      cells (GC) and cumulus cells (CC) is involved in the process of follicular growth
      and maturation. First, to examine the presence of UPR in growing follicles, the
      expression of spliced form of X-box-binding protein 1 (XBP1(S)) and heat shock 70
      kDa protein 5 (HSPA5) mRNA, typical UPR genes, in mice ovaries were examined by
      in situ hybridization. GC of later stage than large secondary follicles expressed
      both XBP1(S) and HSPA5 mRNA, which was accompanied with the activation of ER
      stress sensor proteins, inositol-requiring enzyme 1 (IRE1) and double-stranded
      RNA-activated protein kinase-like ER kinase (PERK), confirmed by
      immunohistochemistry. Next, to examine the association between the fertilization
      capacity of oocytes and the expression levels of UPR genes in surrounding CC,
      human CC were collected from patients undergoing ICSI. The expression levels of
      XBP1(S) mRNA, quantified by RT-PCR, in CC enclosing human oocytes achieving
      fertilization were two-fold higher, than those in CC enclosing oocytes without
      fertilization capacity. In conclusion, UPR is activated during follicular growth
      and suggested to be involved in the process of follicular growth and maturation. 

PMID- 26291813
TI  - Pre-implantation genetic diagnosis and screening: now and the future.
AB  - Since 1989, the year of the first pre-implantation genetic diagnosis (PGD), many
      developments occurred both in assisted reproduction techniques and in molecular
      tools. While PGD is a well-established and documented application, pre
      implantation genetic screening (PGS) for the detection of aneuploid embryos is
      still debated due to the presence of mosaicism in the embryo, but especially to
      the knowledge of the limits that label an embryo as healthy or as appropriate to
      the life. The aim of this review is to present the state-of-the-art in the field
      of PGD and PGS, illustrating its benefits and limitations, along with biopsy
      techniques and the use of new high-throughput technologies. 

PMID- 26291814
TI  - Examination of angiopoietin-like protein 4, neuropeptide Y, omentin-1 levels of
      obese and non-obese patients with polycystic ovary syndrome.
AB  - The pathogenesis of polycystic ovary syndrome (PCOS) and obesity is not clarified
      yet. But some parameters such as neuropeptide Y (NPY), angiopoietin-like protein
      (Angptl-4), omentin-1 are thought to be involved in this pathogenesis. In this
      study, we aimed to show possible effects of NPY, Angptl-4, omentin-1 throughout
      clinical parameters and hormones. Patients were divided into three groups. Group
      I; healthy volunteers, Group II; non-obese women with PCOS and group III; obese
      women with PCOS. Serum NPY, Angptl-4, free testosterone, total testosterone,
      luteinize hormone, sex hormone binding globulin, estradiol,
      dehydroepiandrosterone sulfate, androstenedione, triglycerides and low density
      lipoprotein cholesterol levels and HOMA-IR, Ferriman-Galwey scores were
      significantly higher in group II when compared with group I and similarly in
      group III when compared with group II (p < 0.005). While comparing all PCOS
      patients (obese + non-obese) with healthy volunteers, omentin-1 and high density
      lipoprotein cholesterol levels were significantly low in PCOS group (p < 0.005).
      As a result of this study, both in the obese and non-obese PCOS patients, there
      was a significant increase in levels of NPY and Angptl-4 and a significant
      decline in omentin-1 when compared to healthy subjects. In conclusion, insulin
      resistance in PCOS patients may be related to the differences of NPY, Angptl-4
      and omentin-1 levels and the effects of these differences on metabolic pathways. 

PMID- 26291815
TI  - Effects of subtelomeric copy number variations in miscarriages.
AB  - PURPOSE: This study was performed on miscarriage samples for chromosome analysis
      to detect copy number variations (CNVs) related to subtelomeric regions, and with
      these results we aimed to adapt multiplex ligation-dependent probe amplification
      (MLPA) method for prenatal diagnosis. MATERIALS AND METHODS: The cell cultures
      and DNA isolations were performed on 60 miscarriage samples. For maternal
      contamination analysis, DNA isolations and quantitative fluorescent polymerase
      chain reactions were done using peripheric blood of mothers who had miscarriages.
      We compared short tandem repeat peak profiles of miscarriage samples and mothers.
      The subtelomeric regions of the chromosomes were assessed using the MLPA method.
      RESULTS: Of 43 miscarriage samples, 19 had normal karyotype (44.2%), 10 had
      numerical abnormalities (23.3%), and 2 had structural abnormalities (4.7%).
      Subtelomeric 16q duplication was determined in 2 of the 30 miscarriage samples
      investigated with MLPA method (6.6%). CONCLUSION: There is no statistically
      significant difference between two groups (p > 0.05). However, the fact that the
      6.6% subtelomeric CNV found in miscarriage samples was not found in controls,
      showed that further studies are required. We recommend that the miscarriage
      samples of the couples with recurrent miscarriage should be analyzed in terms of
      subtelomeric CNV after the exclusion of other clinical reasons.

PMID- 26291816
TI  - Are serum chemerin levels different between obese and non-obese polycystic ovary
      syndrome women?
AB  - The objective of this study is to measure serum chemerin levels in women with
      polycystic ovary syndrome (PCOS) and assess their relationship with clinical,
      metabolic, and hormonal parameters. One hundred eighteen PCOS women and 114
      healthy women were recruited in this study. Their blood pressure, body mass index
      (BMI), waist circumference and waist-to-hip ratio (WHR), fasting insulin (FIN),
      fasting plasma glucose (FPG), blood serum sex hormone, and blood lipid were
      measured. Serum chemerin, leptin, and adiponectin were measured by ELISA. Serum
      chemerin was significantly higher in the obese PCOS group (47.62 +/- 11.27 ng/mL)
      compared with non-obese PCOS (37.10 +/- 9.55 ng/mL) and the obese (33.71 +/- 6.17
      ng/mL) and non-obese (25.78 +/- 6.93 ng/mL) control groups (p < 0.05). Serum
      chemerin was positively related to BMI, waist circumference, WHR, testosterone
      (T), FPG, FIN, homeostasis model assessment of insulin resistance (HOMA-IR),
      total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C), LDL
      C/high-density lipoprotein(HDL-C), TC/HDL-C and serum leptin, while negatively
      related to glucose-to-insulin ratio (G/I), HDL-C, and adiponectin levels.
      Multiple linear regression analysis revealed HOMA-IR, leptin, and TC were the
      significant influencing factors of chemerin levels (p < 0.05). Increased serum
      chemerin in PCOS woman with or without obesity suggested that chemerin may be
      involved in the development of the pathogenesis of PCOS. 

PMID- 26291817
TI  - Luteal phase support in intrauterine insemination cycles: a prospective
      randomized study of 300 mg versus 600 mg intravaginal progesterone tablet.
AB  - Vaginal progesterone (P) has been suggested to be used for luteal phase support
      (LPS) in controlled ovarian stimulation (COH)-intrauterine insemination (IUI)
      cycles, however, no concensus exists about the best P dose. Therefore,
      considering the fecundability rate as the primary end point, our main objective
      was to find the optimal dose of P in COH-IUI cycles, comparing the two groups of
      women, each of which comprised of 100 women either on 300 mg or 600 mg of
      intravaginal P tablets, in a prospective randomized study design. The mean age of
      the women, duration of infertility, basal and day of hCG injection hormone levels
      in the female and sperm parameters were similar in the two study groups. Also,
      duration and dose of gonadotropin given, number of follicles, endometrial
      thickness, the total, ongoing and multiple pregnancy rates were comparable in
      both groups. We, therefore, claim that 300 mg of intravaginal micronized P should
      be the maximum dose of LPS in IUI cycles.

PMID- 26291818
TI  - Effects of early and late treatments of low-intensity, high-frequency mechanical
      vibration on bone parameters in rats.
AB  - Low-intensity, high-frequency mechanical vibration (LHMV) has shown to increase
      bone formation. However, studies comparing the effectiveness of early- and late
      treatments of LHMV to counteract bone loss have not been documented. This study
      was designed to compare the effects of early- and late-treatments of LHMV (at 30
      Hz/0.6 g, 20 min per day/five days per week, for 12 weeks) on bone parameters in
      ovariectomized (Ovx) rats. Thirty days after ovariectomy, 40 adult rats were
      randomly divided into four groups: GI (early control group); GII treated with
      LHMV 3 weeks after Ovx (early treatment); GIII (late control group) and GIV
      treated with LHMV twelve weeks after Ovx (late treatment). Bone mineral density
      (BMD) was analyzed before Ovx and after treatments. Then, animals were killed,
      and the femurs were collected and their length and diaphysis diameter were
      measured; the distal femurs were taken and processed for histomorphometry and
      polarized light microscopy for collagen fibers analysis or subjected to
      immunohistochemistry of cleaved caspase-3 in osteocytes. Statistical analysis was
      done by ANOVA followed by the Bonferroni post hoc test (p < 0.05). BMD was
      similar among the groups before Ovx, but after treatments, it was significantly
      higher in GII and GIV compared with their control groups (p < 0.05). Femur length
      and cortical bone thickness were similar among the groups, but the diaphysis
      diameter of GII was higher compared with GI. Trabecular bone area was higher in
      the vibrated groups, but it was greater in GII (p < 0.05). Also, the vibrated
      groups showed the higher content collagen fibers and lower presence apoptotic
      osteocytes (positive caspase-3 immunoreactivity) when compared with the other
      groups (p < 0.05). These results suggest that both early- and late-treatments
      with LHMV counteract bone loss, being the early treatment more effective than the
      late treatment. 

PMID- 26291819
TI  - Transient psychosis in women on clomiphene, bromocriptine, domperidone and
      related endocrine drugs.
AB  - BACKGROUND: There have been reports of transient psychosis in women medicated for
      gynecologic conditions. OBJECTIVE: The aim of this paper was to explore this
      literature. METHOD: The PubMed and Google Scholar databases were searched for
      relevant case reports Results: The following reports were found: psychosis
      induced by gonadotropin-releasing hormone in the treatment of endometriosis, by
      clomiphene treatment for infertility, by bromocriptine treatment for milk
      suppression and by the withdrawal of domperidone prescribed as a galactologue as
      well as by the withdrawal of estrogen replacement therapy. CONCLUSION: In
      susceptible women, psychotic symptoms can result from treatments that reduce
      estrogen levels, such as leuprolide acetate or clomiphene, or treatments that
      increase dopamine levels (bromocriptine). Psychosis can also be caused indirectly
      when estrogen treatment is discontinued or dopamine antagonism (e.g. domperidone)
      withdrawn. Estrogen-reducing and dopamine-increasing treatments used in
      gynecology need to be carefully monitored.

PMID- 26291820
TI  - S100P regulates trophoblast-like cell proliferation via P38 MAPK pathway.
AB  - S100P was originally isolated from the placenta, and is expressed in very high
      levels in trophoblast cells, but its role on trophoblast cells proliferation has
      not yet been studied. In this study, we aimed to investigate the potential role
      of S100P in human placental development, and the impact of its expression
      regulation on cellular function as well as molecular mechanisms involved in
      trophoblast-like cells. We found that the expression of S100P in first trimester
      placenta was significantly reduced in spontaneous abortion patients with respect
      to normal pregnant women. Up-regulation of S100P in JAR cells promoted JAR cells
      proliferation, and increased the expression of phosphorylated P38 (p-P38) mitogen
      activated protein kinase (MAPK) and p-ERK MAPK. However, the effects of S100P on
      JAR cells proliferation were prevented by P38 inhibitor-SB203580, but not by ERK
      inhibitor-PD98059. These results showed that S100P may have a physiological role
      in normal pregnant development, and regulate trophoblast-like cell proliferation
      via modulating the P38 MAPK pathway. 

PMID- 26291821
TI  - Correction: Rapid Microsatellite Identification from Illumina Paired-End Genomic
      Sequencing in Two Birds and a Snake.

PMID- 26291823
TI  - Fish-Free Diet in Patients with Phenylketonuria Is Not Associated with Early
      Atherosclerotic Changes and Enhanced Platelet Activation.
AB  - BACKGROUND AND PURPOSE: Since patients with phenylketonuria (PKU) have to follow
      a lifelong restriction of natural protein to lower phenylalanine-intake, they
      never eat fish. This diet may lead to a chronic deficit of omega-3 and omega-6
      fatty acids with the risk of early atherosclerotic changes. The aim of the study
      was to analyse the fatty acid profile of PKU patients and to correlate the
      results with surrogate markers of early atherosclerotic changes [enhanced carotid
      intima media thickness (CIMT) and beta-stiffness index] and platelet activation.
      METHODS: In 43 PKU patients and in 58 healthy controls we prospectively examined
      the fatty acid profile, CIMT, beta-stiffness index and platelet activation (flow
      cytometric determination of markers of platelet activation). CIMT was measured
      bilaterally by ultrasound. CIMTmean was defined as the mean value of the sum of
      CIMTleft and CIMTright. RESULTS: Despite of lower HDL-cholesterol and higher
      triglyceride concentrations in the PKU group, there was no significant difference
      in the omega-6 or omega-3 fatty acid profile, CIMT, beta-stiffness index between
      both groups. Platelet activation was not enhanced in the PKU group. CONCLUSIONS:
      Fish-free diet does not induce early atherosclerotic changes or enhanced platelet
      activation in PKU patients.

PMID- 26291822
TI  - Which Way In? The RalF Arf-GEF Orchestrates Rickettsia Host Cell Invasion.
AB  - Bacterial Sec7-domain-containing proteins (RalF) are known only from species of
      Legionella and Rickettsia, which have facultative and obligate intracellular
      lifestyles, respectively. L. pneumophila RalF, a type IV secretion system (T4SS)
      effector, is a guanine nucleotide exchange factor (GEF) of ADP-ribosylation
      factors (Arfs), activating and recruiting host Arf1 to the Legionella-containing
      vacuole. In contrast, previous in vitro studies showed R. prowazekii (Typhus
      Group) RalF is a functional Arf-GEF that localizes to the host plasma membrane
      and interacts with the actin cytoskeleton via a unique C-terminal domain. As RalF
      is differentially encoded across Rickettsia species (e.g., pseudogenized in all
      Spotted Fever Group species), it may function in lineage-specific biology and
      pathogenicity. Herein, we demonstrate RalF of R. typhi (Typhus Group) interacts
      with the Rickettsia T4SS coupling protein (RvhD4) via its proximal C-terminal
      sequence. RalF is expressed early during infection, with its inactivation via
      antibody blocking significantly reducing R. typhi host cell invasion. For R.
      typhi and R. felis (Transitional Group), RalF ectopic expression revealed
      subcellular localization with the host plasma membrane and actin cytoskeleton.
      Remarkably, R. bellii (Ancestral Group) RalF showed perinuclear localization
      reminiscent of ectopically expressed Legionella RalF, for which it shares several
      structural features. For R. typhi, RalF co-localization with Arf6 and PI(4,5)P2
      at entry foci on the host plasma membrane was determined to be critical for
      invasion. Thus, we propose recruitment of PI(4,5)P2 at entry foci, mediated by
      RalF activation of Arf6, initiates actin remodeling and ultimately facilitates
      bacterial invasion. Collectively, our characterization of RalF as an invasin
      suggests that, despite carrying a similar Arf-GEF unknown from other bacteria,
      different intracellular lifestyles across Rickettsia and Legionella species have
      driven divergent roles for RalF during infection. Furthermore, our identification
      of lineage-specific Arf-GEF utilization across some rickettsial species
      illustrates different pathogenicity factors that define diverse agents of
      rickettsial diseases. 

PMID- 26291825
TI  - Response to Fustran et al. 'Postoperative analgesia with continuous wound
      infusion of local anaesthesia vs saline: a double-blind randomized, controlled
      trial in colorectal surgery'.

PMID- 26291824
TI  - Higher Frequency of NK and CD4+ T-Cells in Mucosa and Potent Cytotoxic Response
      in HIV Controllers.
AB  - HIV infection induces immune alterations, mainly in gut mucosa, where the main
      target cells reside. However, the evolution of the infection is variable among
      infected individuals, as evidenced by HIV controllers who exhibit low or
      undetectable viral load in the absence of treatment. The aim of this study was to
      evaluate the frequency, phenotype and activity of T and NK cells in peripheral
      blood and gut mucosa in a cohort of Colombian HIV controllers. Blood and gut
      biopsies were included. The frequency and the activation status of T and NK cells
      were performed by flow cytometry. In addition, Gag-stimulated CD8+ T-cells and
      cytokine-stimulated NK cells were tested for cytotoxic activity. Finally,
      microbial translocation was measured by plasma lipopolysaccharide quantification.
      Compared with HIV-progressors, HIV controllers exhibited higher frequency of CD4+
      T and NK cells, and lower expression of activation molecules in blood and mucosal
      immune cells, as well as lower microbial translocation. An increased production
      of molecules associated with cytotoxic activity of CD8+ T-cells in blood and
      mucosa and a higher percentage of polyfunctional CD8+ T cells in blood were also
      observed in HIV controllers. In addition, an increased activity of NK cells was
      observed in blood. These findings suggest that HIV controllers have a potent
      immune response, mainly mediated by cytotoxic cells that control HIV replication,
      which contribute to reducing alterations at the gut mucosa. 

PMID- 26291826
TI  - Emergence of One-Dimensional Wires of Free Carriers in Transition-Metal
      Dichalcogenide Nanostructures.
AB  - We highlight the emergence of metallic states in two-dimensional transition-metal
      dichalcogenide nanostructures-nanoribbons, islands, and inversion domain
      boundaries-as a widespread and universal phenomenon driven by the polar
      discontinuities occurring at their edges or boundaries. We show that such
      metallic states form one-dimensional wires of electrons or holes, with a free
      charge density that increases with the system size, up to complete screening of
      the polarization charge, and can also be controlled by the specific edge or
      boundary configurations, e.g., through chemisorption of hydrogen or sulfur atoms
      at the edges. For triangular islands, local polar discontinuities occur even in
      the absence of a total dipole moment for the island and lead to an accumulation
      of free carriers close to the edges, providing a consistent explanation of
      previous experimental observations. To further stress the universal character of
      these mechanisms, we show that polar discontinuities give rise to metallic states
      also at inversion domain boundaries. These findings underscore the potential of
      engineering transition-metal-dichalcogenide nanostructures for manifold
      applications in nano- and optoelectronics, spintronics, catalysis, and solar
      energy harvesting. 

PMID- 26291827
TI  - Dual-mode T1 and T2 magnetic resonance imaging contrast agent based on ultrasmall
      mixed gadolinium-dysprosium oxide nanoparticles: synthesis, characterization, and
      in vivo application.
AB  - A new type of dual-mode T1 and T2 magnetic resonance imaging (MRI) contrast agent
      based on mixed lanthanide oxide nanoparticles was synthesized. Gd(3+) ((8)S7/2)
      plays an important role in T1 MRI contrast agents because of its large electron
      spin magnetic moment resulting from its seven unpaired 4f-electrons, and Dy(3+)
      ((6)H15/2) has the potential to be used in T2 MRI contrast agents because of its
      very large total electron magnetic moment: among lanthanide oxide nanoparticles,
      Dy2O3 nanoparticles have the largest magnetic moments at room temperature. Using
      these properties of Gd(3+) and Dy(3+) and their oxide nanoparticles, ultrasmall
      mixed gadolinium-dysprosium oxide (GDO) nanoparticles were synthesized and their
      potential to act as a dual-mode T1 and T2 MRI contrast agent was investigated in
      vitro and in vivo. The D-glucuronic acid coated GDO nanoparticles (davg = 1.0 nm)
      showed large r1 and r2 values (r2/r1 ~ 6.6) and as a result clear dose-dependent
      contrast enhancements in R1 and R2 map images. Finally, the dual-mode imaging
      capability of the nanoparticles was confirmed by obtaining in vivo T1 and T2 MR
      images. 

PMID- 26291828
TI  - An Efficient and Versatile System for Visualization and Genetic Modification of
      Dopaminergic Neurons in Transgenic Mice.
AB  - BACKGROUND & AIMS: The brain dopaminergic (DA) system is involved in fine tuning
      many behaviors and several human diseases are associated with pathological
      alterations of the DA system such as Parkinson's disease (PD) and drug addiction.
      Because of its complex network integration, detailed analyses of physiological
      and pathophysiological conditions are only possible in a whole organism with a
      sophisticated tool box for visualization and functional modification. METHODS &
      RESULTS: Here, we have generated transgenic mice expressing the tetracycline
      regulated transactivator (tTA) or the reverse tetracycline-regulated
      transactivator (rtTA) under control of the tyrosine hydroxylase (TH) promoter, TH
      tTA (tet-OFF) and TH-rtTA (tet-ON) mice, to visualize and genetically modify DA
      neurons. We show their tight regulation and efficient use to overexpress proteins
      under the control of tet-responsive elements or to delete genes of interest with
      tet-responsive Cre. In combination with mice encoding tet-responsive luciferase,
      we visualized the DA system in living mice progressively over time. CONCLUSION:
      These experiments establish TH-tTA and TH-rtTA mice as a powerful tool to
      generate and monitor mouse models for DA system diseases.

PMID- 26291830
TI  - Multidrug-Resistance Related Long Non-Coding RNA Expression Profile Analysis of
      Gastric Cancer.
AB  - The effect of chemotherapy of gastric cancer (GC) remains very poor because of
      multidrug resistance (MDR). However, the mechanisms underlying MDR of GC remains
      far from fully understood. The aim of this study is to illustrate the potential
      mechanisms of the MDR of GC at mainly the long non-coding RNA (lncRNA) level. In
      this study, GC cell line, SGC7901, and two MDR sublines, SGC7901/VCR and
      SGC7901/ADR were subjected to an lncRNA microarray analysis. Bioinformatics and
      verification experiments were performed to investigate the potential lncRNAs
      involved in the development of MDR. Pathway analysis indicated that 15 pathways
      corresponded to down-regulated transcripts and that 20 pathways corresponded to
      up-regulated transcripts (p-value cut-off is 0.05). GO analysis showed that the
      highest enriched GOs targeted by up-regulated transcripts were "system
      development" and the highest esenriched GOs targeted by the down-regulated
      transcripts were "sterol biosynthetic process". Our study is the first to
      interrogate differentially expressed lncRNAs in human GC cell line and MDR
      sublines and indicates that lncRNAs are worthwhile for further study to be the
      novel candidate biomarkers for the clinical diagnosis of MDR and potential
      targets for further therapy. 

PMID- 26291832
TI  - Reprint of "Steroid receptor coactivators as therapeutic targets in the female
      reproductive system".
AB  - The steroid receptor coactivators (SRCs/p160/NCOA) are a family of three
      transcriptional coregulators initially discovered to transactivate the
      transcriptional potency of steroid hormone receptors. Even though SRCs were also
      found to modulate the activity of multiple other transcription factors, their
      function is still strongly associated with regulation of steroid hormone action
      and many studies have found that they are critical for the regulation of
      reproductive biology. In the case of the female reproductive tract, SRCs have
      been found to play crucial roles in its physiology, ranging from ovulation,
      implantation, to parturition. Not surprisingly, SRCs' action has been linked to
      numerous abnormalities and debilitating disorders of female reproductive tissues,
      including infertility, cancer, and endometriosis. Many of these pathologies are
      still in critical need of therapeutic intervention and "proof-of-principle"
      studies have found that SRCs are excellent targets in pathological states.
      Therefore, small molecule modulators of SRCs' activity could be applied in the
      future in the treatment of many diseases of the female reproductive system. 

PMID- 26291829
TI  - 30-Year Trends in Stroke Rates and Outcome in Auckland, New Zealand (1981-2012):
      A Multi-Ethnic Population-Based Series of Studies.
AB  - BACKGROUND: Insufficient data exist on population-based trends in morbidity and
      mortality to determine the success of prevention strategies and improvements in
      health care delivery in stroke. The aim of this study was to determine trends in
      incidence and outcome (1-year mortality, 28-day case-fatality) in relation to
      management and risk factors for stroke in the multi-ethnic population of
      Auckland, New Zealand (NZ) over 30-years. METHODS: Four stroke incidence
      population-based register studies were undertaken in adult residents (aged >=15
      years) of Auckland NZ in 1981-1982, 1991-1992, 2002-2003 and 2011-2012. All used
      standard World Health Organization (WHO) diagnostic criteria and multiple
      overlapping sources of case-ascertainment for hospitalised and non-hospitalised,
      fatal and non-fatal, new stroke events. Ethnicity was consistently self
      identified into four major groups. Crude and age-adjusted (WHO world population
      standard) annual incidence and mortality with corresponding 95% confidence
      intervals (CI) were calculated per 100,000 people, assuming a Poisson
      distribution. RESULTS: 5400 new stroke patients were registered in four 12 month
      recruitment phases over the 30-year study period; 79% were NZ/European, 6% Maori,
      8% Pacific people, and 7% were of Asian or other origin. Overall stroke incidence
      and 1-year mortality decreased by 23% (95% CI 5%-31%) and 62% (95% CI 36%-86%),
      respectively, from 1981 to 2012. Whilst stroke incidence and mortality declined
      across all groups in NZ from 1991, Maori and Pacific groups had the slowest rate
      of decline and continue to experience stroke at a significantly younger age (mean
      ages 60 and 62 years, respectively) compared with NZ/Europeans (mean age 75
      years). There was also a decline in 28-day stroke case fatality (overall by 14%,
      95% CI 11%-17%) across all ethnic groups from 1981 to 2012. However, there were
      significant increases in the frequencies of pre-morbid hypertension, myocardial
      infarction, and diabetes mellitus, but a reduction in frequency of current
      smoking among stroke patients. CONCLUSIONS: In this unique temporal series of
      studies spanning 30 years, stroke incidence, early case-fatality and 1-year
      mortality have declined, but ethnic disparities in risk and outcome for stroke
      persisted suggesting that primary stroke prevention remains crucial to reducing
      the burden of this disease.

PMID- 26291833
TI  - Reprint of "Why both LC-MS/MS and FDA-compliant validation are essential for
      accurate estrogen assays?".

PMID- 26291834
TI  - Reprint of "Use of medroxyprogesterone acetate for hormone therapy in
      postmenopausal women: Is it safe?".
AB  - Medroxyprogesterone acetate (MPA) has been in clinical use for over 30 years, and
      was generally considered to be safe until the results of long-term studies of
      postmenopausal hormone therapy (HT) using treatment with conjugated equine
      estrogens (CEE) combined with MPA and CEE alone suggested that MPA, and perhaps
      other progestogens, may play a role in the increased risk of breast cancer and
      cardiovascular diseases. This review examines critically the safety of MPA in
      terms of breast cancer and cardiovascular disease risk, and its effects on brain
      function. Research into mechanisms by which MPA might cause adverse effects in
      these areas, combined with the available clinical evidence, suggests a small
      increase in relative risk for breast cancer and stroke, and a decline in
      cognitive function, in older women using MPA with an estrogen for postmenopausal
      HT. However, short-term (less than 5 years) use of MPA with an estrogen in the
      years immediately after the onset of menopause for the management of vasomotor
      symptoms does not appear to be associated with any increased risk of these
      disorders. 

PMID- 26291831
TI  - CD4+CD25hiFOXP3+ Regulatory T Cells and Cytokine Responses in Human
      Schistosomiasis before and after Treatment with Praziquantel.
AB  - BACKGROUND: Chronic schistosomiasis is associated with T cell hypo-responsiveness
      and immunoregulatory mechanisms, including induction of regulatory T cells
      (Tregs). However, little is known about Treg functional capacity during human
      Schistosoma haematobium infection. METHODOLOGY: CD4+CD25hiFOXP3+ cells were
      characterized by flow cytometry and their function assessed by analysing total
      and Treg-depleted PBMC responses to schistosomal adult worm antigen (AWA),
      soluable egg antigen (SEA) and Bacillus Calmette-Guerin (BCG) in S. haematobium
      infected Gabonese children before and 6 weeks after anthelmintic treatment.
      Cytokines responses (IFN-gamma, IL-5, IL-10, IL-13, IL-17 and TNF) were
      integrated using Principal Component Analysis (PCA). Proliferation was measured
      by CFSE. PRINCIPAL FINDINGS: S. haematobium infection was associated with
      increased Treg frequencies, which decreased post-treatment. Cytokine responses
      clustered into two principal components reflecting regulatory and Th2-polarized
      (PC1) and pro-inflammatory and Th1-polarized (PC2) cytokine responses; both
      components increased post-treatment. Treg depletion resulted in increased PC1 and
      PC2 at both time-points. Proliferation on the other hand, showed no significant
      difference from pre- to post-treatment. Treg depletion resulted mostly in
      increased proliferative responses at the pre-treatment time-point only.
      CONCLUSIONS: Schistosoma-associated CD4+CD25hiFOXP3+Tregs exert a suppressive
      effect on both proliferation and cytokine production. Although Treg frequency
      decreases after praziquantel treatment, their suppressive capacity remains
      unaltered when considering cytokine production whereas their influence on
      proliferation weakens with treatment.

PMID- 26291835
TI  - Reprint of "In vitro and in vivo evaluation of a 3beta-androsterone derivative as
      inhibitor of 17beta-hydroxysteroid dehydrogenase type 3".
AB  - 17beta-Hydroxysteroid dehydrogenase type 3 (17beta-HSD3 or HSD17B3) catalyzes the
      last step in the biosynthesis of the potent androgen testosterone (T), by
      stereoselectively reducing the C17 ketone of 4-androstene-3,17-dione (4-dione),
      with NADPH as cofactor. Since T plays an important role in androgen-sensitive
      diseases, this enzyme is thus an interesting therapeutic target. In an attempt to
      design compounds to lower the level of T, we synthesized androsterone derivatives
      substituted at position 3 as inhibitors of 17beta-HSD3, and selected one of the
      most potent compounds for additional studies. In an enzymatic assay in
      homogenized and whole HEK-293 cells overexpressing 17beta-HSD3, the inhibitor RM
      532-105 efficiently inhibited the conversion of natural substrate 4-dione (50nM)
      into T with an IC50 of 26nM and 5nM, respectively. Moreover, the inhibitor RM-532
      105 (10mg/kg) reached a plasma concentration of 250ng/mL at 7h (AUC 24h:
      3485ngh/mL) after subcutaneous (s.c.) injection in the rat. In order to mimic the
      human situation in which 4-dione is converted to T in the testis, we used intact
      rats. Treatment for 7 days with 17beta-HSD3 inhibitor RM-532-105 by s.c.
      injection or oral gavage exerted no effect on the testis, prostate and seminal
      vesicle weight and no modification in the levels of plasma steroids. However,
      after this treatment, the concentration of inhibitor in plasma increased
      depending on the dose. We thereafter determined the concentration of inhibitor in
      the testis and we discovered that the compound was slightly present. In fact, at
      10mg/kg, the inhibitor RM-532-105 seems to have difficulty penetrating inside the
      testis and was found to be concentrated in the testicular capsule, and therefore
      unable to inhibit the 17beta-HSD3 located inside the testis. However, with a
      higher dose of 50mg/kg injected s.c. in rats, RM-532-105 significantly decreased
      the level of T and dihydrotestosterone measured in plasma at 2h. 

PMID- 26291836
TI  - Reprint of "In silico methods in the discovery of endocrine disrupting
      chemicals".
AB  - The prevalence of sex hormone-dependent cancers, reproductive problems, obesity,
      and cardiovascular complications has risen especially in the Western world. It
      has been suggested, that the exposure to various endocrine disrupting chemicals
      (EDCs) contributes to the development and progression of these diseases. EDCs can
      interfere with various proteins: nuclear steroid hormone receptors, such as
      estrogen-, androgen-, glucocorticoid- and mineralocorticoid receptors (ER, AR,
      GR, MR), and enzymes that are involved in steroid hormone synthesis and
      metabolism, for example hydroxysteroid dehydrogenases (HSDs). Numerous chemicals
      are known as endocrine disruptors. However, the mechanism of action for most of
      these EDCs is still unknown. It is exhaustive and time consuming to test in vitro
      all chemicals - potential EDCs - used in industry, agriculture or as food
      preservatives against their effects on the endocrine system. Computational
      methods, such as virtual screening, quantitative structure activity relationships
      and docking, are already well recognized and used in drug development. The same
      methods could also aid the research on EDCs. So far, the computational methods in
      the search of EDCs have been retrospective. There are, however, some prospective
      studies reporting the use of in silico methods: five studies reporting the
      identification of previously unknown 17beta-HSD3 inhibitors, MR agonists, and ER
      antagonists/agonists. This review provides an overview of case studies and in
      silico methods that are used in the search of EDCs. This article is part of a
      Special Issue entitled 'CSR 2013'. 

PMID- 26291838
TI  - Self-Assembly, Supramolecular Organization, and Phase Behavior of L-Alanine Alkyl
      Esters (n = 9-18) and Characterization of Equimolar L-Alanine Lauryl Ester/Lauryl
      Sulfate Catanionic Complex.
AB  - A homologous series of l-alanine alkyl ester hydrochlorides (AEs) bearing 9-18 C
      atoms in the alkyl chain have been synthesized and characterized with respect to
      self-assembly, supramolecular structure, and phase transitions. The CMCs of AEs
      bearing 11-18 C atoms were found to range between 0.1 and 10 mM. Differential
      scanning calorimetric (DSC) studies showed that the transition temperatures (Tt),
      enthalpies (DeltaHt) and entropies (DeltaSt) of AEs in the dry state exhibit odd
      even alternation, with the odd-chain-length compounds having higher Tt values,
      but the even-chain-length homologues showing higher values of DeltaHt and
      DeltaSt. In DSC measurements on hydrated samples, carried out at pH 5.0 and pH
      10.0 (where they exist in cationic and neutral forms, respectively), compounds
      with 13-18 C atoms in the alkyl chain showed sharp gel-to-liquid crystalline
      phase transitions, and odd-even alternation was not seen in the thermodynamic
      parameters. The molecular structure, packing properties, and intermolecular
      interactions of AEs with 9 and 10 C atoms in the alkyl chain were determined by
      single crystal X-ray diffraction, which showed that the alkyl chains are packed
      in a tilted interdigitated bilayer format. d-Spacings obtained from powder X-ray
      diffraction studies exhibited a linear dependence on the alkyl chain length,
      suggesting that the other AEs also adopt an interdigitated bilayer structure.
      Turbidimetric, fluorescence spectroscopic, and isothermal titration calorimetric
      (ITC) studies established that in aqueous dispersions l-alanine lauryl ester
      hydrochloride (ALE.HCl) and sodium dodecyl sulfate (SDS) form an equimolar
      complex. Transmission electron microscopic and DSC studies indicate that the
      complex exists as unilamellar liposomes, which exhibit a sharp phase transition
      at ~39  degrees C. The aggregates were disrupted at high pH, suggesting that the
      catanionic complex would be useful to develop a base-labile drug delivery system.
      ITC studies indicated that ALE.HCl forms a strong complex with DNA, suggesting
      that the AEs may find use in DNA therapeutics as well. 

PMID- 26291839
TI  - Laboratory Testing for Middle East Respiratory Syndrome Coronavirus, California,
      USA, 2013-2014.
AB  - Since Middle East respiratory syndrome coronavirus (MERS-CoV) first emerged, the
      California Department of Public Health has coordinated efforts to identify
      possible cases in travelers to California, USA, from affected areas. During 2013
      2014, the department investigated 54 travelers for MERS-CoV; none tested
      positive, but 32 (62%) of 52 travelers with suspected MERS-CoV had other
      respiratory viruses. 

PMID- 26291840
TI  - Deletion status of p16 in effusion smear preparation correlates with that of
      underlying malignant pleural mesothelioma tissue.
AB  - Differentiating malignant pleural mesothelioma (MPM) cells morphologically from
      reactive mesothelial hyperplasia cells is problematic. Homozygous deletion (HD)
      of p16 (CDKN2A), detected by FISH, is a good marker of malignancy and is useful
      to differentiate between these cells. However, the correlation between the p16
      status of effusion smears and that of the underlying MPM tissues has not been
      investigated. We used p16-specific FISH to investigate 20 cases of MPM from which
      both effusion cytologic smears and histologic specimens were available. In five
      cases, histologic specimens included both an invasive component and surface
      mesothelial proliferation. In 14 cases (70%), MPM cells in both tissue sections
      and effusion smears were p16 HD-positive. Conversely, MPM cells in the remaining
      six tumors (30%) were p16 HD-negative in both tissue sections and effusion
      smears. For all five MPM cases with surface mesothelial proliferations and
      invasive components, the effusion smears, surface mesothelial proliferations, and
      invasive MPM components all displayed p16 deletion. Moreover, the extent to which
      p16 was deleted in smears highly correlated with the extent of p16 deletion in
      tissues. The p16 deletion percentages were also similar among smears, tissue
      surface proliferations, and invasive components. In cases with clinical and
      radiologic evidence of a diffuse pleural tumor, detection of p16 deletion in
      cytologic smear samples may permit MPM diagnosis without additional tissue
      examination. However, the absence of p16 deletion in cytologic smear samples does
      not preclude MPM. 

PMID- 26291845
TI  - Vibrational fingerprint mapping reveals spatial distribution of functional groups
      of lignin in plant cell wall.
AB  - Highly lignified vascular plant cell walls represent the majority of cellulosic
      biomass. Complete release of the biomass to deliver renewable energy by physical,
      chemical, and biological pretreatments is challenging due to the "protection"
      provided by polymerized lignin, and as such, additional tools to monitor lignin
      deposition and removal during plant growth and biomass deconstruction would be of
      great value. We developed a hyperspectral stimulated Raman scattering microscope
      with 9 cm(-1) spectral resolution and submicrometer spatial resolution. Using
      this platform, we mapped the aromatic ring of lignin, aldehyde, and alcohol
      groups in lignified plant cell walls. By multivariate curve resolution of the
      hyperspectral images, we uncovered a spatially distinct distribution of aldehyde
      and alcohol groups in the thickened secondary cell wall. These results
      collectively contribute to a deeper understanding of lignin chemical composition
      in the plant cell wall. 

PMID- 26291841
TI  - High-fat Diet Promotes Cardiac Remodeling in an Experimental Model of Obesity.
AB  - BACKGROUND: Although nutritional, metabolic and cardiovascular abnormalities are
      commonly seen in experimental studies of obesity, it is uncertain whether these
      effects result from the treatment or from body adiposity. OBJECTIVE: To evaluate
      the influence of treatment and body composition on metabolic and cardiovascular
      aspects in rats receiving high saturated fat diet. METHODS: Sixteen Wistar rats
      were used, distributed into two groups, the control (C) group, treated with
      isocaloric diet (2.93 kcal/g) and an obese (OB) group, treated with high-fat diet
      (3.64 kcal/g). The study period was 20 weeks. Analyses of nutritional behavior,
      body composition, glycemia, cholesterolemia, lipemia, systolic arterial pressure,
      echocardiography, and cardiac histology were performed. RESULTS: High-fat diet
      associates with manifestations of obesity, accompanied by changes in glycemia,
      cardiomyocyte hypertrophy, and myocardial interstitial fibrosis. After adjusting
      for adiposity, the metabolic effects were normalized, whereas differences in
      morphometric changes between groups were maintained. CONCLUSION: It was concluded
      that adiposity body composition has a stronger association with metabolic
      disturbances in obese rodents, whereas the high-fat dietary intervention is found
      to be more related to cardiac morphological changes in experimental models of
      diet-induced obesity.

PMID- 26291846
TI  - Serving as a Witness in the Court: Trials, Testimony, and Truth.

PMID- 26291847
TI  - Psychological Outcomes After a Sexual Assault Video Intervention: A Randomized
      Trial.
AB  - Sexual assault survivors are at risk for a number of mental and physical health
      problems, including posttraumatic stress disorder and anxiety. Unfortunately, few
      seek physical or mental health services after a sexual assault (Price, Davidson,
      Ruggiero, Acierno, & Resnick, 2014). Mitigating the impact of sexual assault via
      early interventions is a growing and important area of research. This study adds
      to this literature by replicating and expanding previous studies (e.g., Resnick,
      Acierno, Amstadter, Self-Brown, & Kilpatrick, 2007) examining the efficacy of a
      brief video-based intervention that provides psychoeducation and modeling of
      coping strategies to survivors at the time of a sexual assault nurse examination.
      Female sexual assault survivors receiving forensic examinations were randomized
      to standard care or to the video intervention condition (N = 164). The
      participants completed mental health assessments 2 weeks (n = 69) and 2 months (n
      = 74) after the examination. Analyses of covariance revealed that women in the
      video condition had significantly fewer anxiety symptoms at the follow-up
      assessments. In addition, of those participants in the video condition, survivors
      reporting no previous sexual assault history reported significantly fewer
      posttraumatic stress symptoms 2 weeks after the examination than those with a
      prior assault history. Forensic nurses have the unique opportunity to intervene
      immediately after a sexual assault. This brief video intervention is a cost
      effective tool to aid with that process. 

PMID- 26291837
TI  - Connecting the dots: chromatin and alternative splicing in EMT.
AB  - Nature has devised sophisticated cellular machinery to process mRNA transcripts
      produced by RNA Polymerase II, removing intronic regions and connecting exons
      together, to produce mature RNAs. This process, known as splicing, is very
      closely linked to transcription. Alternative splicing, or the ability to produce
      different combinations of exons that are spliced together from the same genomic
      template, is a fundamental means of regulating protein complexity. Similar to
      transcription, both constitutive and alternative splicing can be regulated by
      chromatin and its associated factors in response to various signal transduction
      pathways activated by external stimuli. This regulation can vary between
      different cell types, and interference with these pathways can lead to changes in
      splicing, often resulting in aberrant cellular states and disease. The epithelial
      to mesenchymal transition (EMT), which leads to cancer metastasis, is influenced
      by alternative splicing events of chromatin remodelers and epigenetic factors
      such as DNA methylation and non-coding RNAs. In this review, we will discuss the
      role of epigenetic factors including chromatin, chromatin remodelers, DNA
      methyltransferases, and microRNAs in the context of alternative splicing, and
      discuss their potential involvement in alternative splicing during the EMT
      process. 

PMID- 26291848
TI  - Does Sexual Assault Nurse Examiner (SANE) Training Affect Attitudes of Emergency
      Department Nurses Toward Sexual Assault Survivors?
AB  - There are over 243,800 female sexual assaults in the United States annually. Of
      those who seek healthcare services after being sexually assaulted, 90% present to
      hospitals. Unfortunately, care and services for women who have been sexually
      assaulted are inconsistent. Increased burnout, frustration, and feelings of
      inadequacy can lead healthcare providers to exhibit personal biases or negative
      attitudes toward their patients. The Joint Commission, responsible for
      accreditation of healthcare organizations, has stated that nurses must provide
      competent care to all patients. Therefore, Sexual Assault Nurse Examiner (SANE)
      training needs to be available for emergency department (ED) nurses who care for
      patients who have been sexually assaulted. A survey using the Attitude Toward
      Rape Victims Scale was sent to 1503 ED nurses throughout the United States, from
      the Emergency Nursing Association's mailing list. The results of the survey
      showed that there was a significant difference in attitudes toward the patients
      between SANE-trained emergency nurses and those without training. This study also
      showed that 35.5% of hospitals represented by the respondents did not have SANE
      services available for adult patients who had been sexually assaulted, and
      furthermore, 85.5% of the respondents who cared for adult patients who had been
      sexually assaulted were not SANE trained. The negative attitudes held toward such
      patients as found in this study, coupled with a lack of training provides
      evidence that ED nurses may benefit from education related to appropriate
      treatment for patients who have been sexually assaulted. As evidence-based
      practice becomes the gold standard of care, ensuring that nurses are properly
      trained to care for all patients must be the goal. 

PMID- 26291850
TI  - Solvent Effect on the Pore-Size Dependence of an Organic Electrolyte
      Supercapacitor.
AB  - Organic electrolytes such as tetraethylammonium tetrafluoroborate dissolved in
      acetonitrile (TEA-BF4/ACN) are widely used in commercial supercapacitors and
      academic research, but conflicting experimental results have been reported
      regarding the dependence of surface-area-normalized capacitance on the pore size.
      Here we show from a classical density functional theory the dependence of
      capacitance on the pore size from 0.5 to 3.0 nm for a model TEA-BF4/ACN
      electrolyte. We find that the capacitance-pore size curve becomes roughly flat
      after the first peak around the ion diameter, and the peak capacitance is not
      significantly higher than the large-pore average. We attribute the invariance of
      capacitance with the pore size to the formation of an electric double-layer
      structure that consists of counterions and highly organized solvent molecules.
      This work highlights the role of the solvent molecules in modulating the
      capacitance and reconciles apparently conflicting experimental reports. 

PMID- 26291851
TI  - Voltage Dependent Charge Storage Modes and Capacity in Subnanometer Pores.
AB  - Using molecular dynamics simulations, we show that charge storage in subnanometer
      pores follows a distinct voltage-dependent behavior. Specifically, at lower
      voltages, charge storage is achieved by swapping co-ions in the pore with
      counterions in the bulk electrolyte. As voltage increases, further charge storage
      is due mainly to the removal of co-ions from the pore, leading to a capacitance
      increase. The capacitance eventually reaches a maximum when all co-ions are
      expelled from the pore. At even higher electrode voltages, additional charge
      storage is realized by counterion insertion into the pore, accompanied by a
      reduction of capacitance. The molecular mechanisms of these observations are
      elucidated and provide useful insight for optimizing energy storage based on
      supercapacitors. 

PMID- 26291852
TI  - A (Nearly) Universally Applicable Method for Modeling Noncovalent Interactions
      Using B3LYP.
AB  - B3LYP is the most widely used density-functional theory (DFT) approach because it
      is capable of accurately predicting molecular structures and other properties.
      However, B3LYP is not able to reliably model systems in which noncovalent
      interactions are important. Here we present a method that corrects this
      deficiency in B3LYP by using dispersion-correcting potentials (DCPs). DCPs are
      utilized by simple modifications to input files and can be used in any
      computational package that can read effective-core potentials. Therefore, the
      technique requires no programming. DCPs (developed for H, C, N, and O) produce
      the best results when used in conjunction with 6-31+G(2d,2p) basis sets. The
      B3LYP-DCP approach was tested on the S66, S22, and HSG-A benchmark sets of
      noncovalently interacting dimers and trimers and was found to, on average,
      significantly outperform almost all other DFT-based methods that were designed to
      treat van der Waals interactions. Users of B3LYP who wish to model systems in
      which noncovalent interactions (viz., steric repulsion, hydrogen bonding, pi
      stacking) are present, should consider B3LYP-DCP. 

PMID- 26291853
TI  - Correction to "Quantum Phenomena in Structural Glasses: The Intrinsic Origin of
      Electronic and Cryogenic Anomalies".

PMID- 26291854
TI  - Graphene-Based Chemical Sensors.
AB  - Pioneering research in 2004 by Geim and Novoselov (2010 Nobel Prize winners in
      Physics) of the University of Manchester led to the isolation of a monolayer
      graphene sheet. Graphene is a single-atom-thick sheet of sp(2) hybridized carbon
      atoms that are packed in a hexagonal honeycomb crystalline structure. Graphene is
      the fundamental building block of all sp(2) carbon materials including single
      walled carbon nanotubes, mutliwalled carbon nanotubes, and graphite and is
      therefore interesting from the fundamental standpoint as well as for practical
      applications. One of the most promising applications of graphene that has emerged
      so far is its utilization as an ultrasensitive chemical or gas sensor. In this
      article, we review some of the significant work performed with graphene and its
      derivatives for gas detection and provide a perspective on the challenges that
      need to be overcome to enable commercially viable graphene chemical sensor
      technologies. 

PMID- 26291855
TI  - Electronic Structures of Formic Acid (HCOOH) and Formate (HCOO(-)) in Aqueous
      Solutions.
AB  - The electronic structures of formic acid (HCOOH) and formate (HCOO(-)) have been
      determined in aqueous solutions over a pH range of 1.88-8.87 using a combination
      of X-ray photoelectron spectroscopy (XPS), partial electron-yield X-ray
      absorption spectroscopy (PEY XAS), and density functional theory (DFT). The
      carbon 1s XPS measurements reveal a binding energy shift of -1.3 eV for
      deprotonated HCOO(-) compared with neutral HCOOH. Such distinction between
      neutral HCOOH and deprotonated HCOO(-) cannot be made based solely on the
      respective carbon K-edge PEY XA spectra. Independent of pH, the C1s -> pi* state
      excitations occur at 288.0 eV and may lead to the incorrect conclusion that the
      energy levels of the pi* state are the same for both species. The DFT
      calculations are consistent with the experimental observations and show a shift
      to higher energy for both the occupied C1s (lower binding energy) and unoccupied
      pi* orbitals of deprotonated HCOO(-) compared to neutral HCOOH in aqueous
      solutions. 

PMID- 26291856
TI  - Effect of Dimensionality on the Photocatalytic Behavior of Carbon-Titania
      Nanosheet Composites: Charge Transfer at Nanomaterial Interfaces.
AB  - Due to their unique optoelectronic structure and large specific surface area,
      carbon nanomaterials have been integrated with titania to enhance photocatalysis.
      In particular, recent work has shown that nanocomposite photocatalytic
      performance can be improved by minimizing the covalent defect density of the
      carbon component. Herein, carbon nanotube-titania nanosheet and graphene-titania
      nanosheet composites with low carbon defect densities are compared to investigate
      the role of carbon nanomaterial dimensionality on photocatalytic response. The
      resulting 2D-2D graphene-titania nanosheet composites yield superior electronic
      coupling compared to 1D-2D carbon nanotube-titania nanosheet composites, leading
      to greater enhancement factors for CO2 photoreduction under ultraviolet
      irradiation. On the other hand, 1D carbon nanotubes are shown to be more
      effective titania photosensitizers, leading to greater photoactivity enhancement
      factors under visible illumination. Overall, this work suggests that carbon
      nanomaterial dimensionality is a key factor in determining the spectral response
      and reaction specificity of carbon-titania nanosheet composite photocatalysts. 

PMID- 26291857
TI  - Toward Ab Initio Anharmonic Vibrational Circular Dichroism Spectra in the
      Condensed Phase.
AB  - The first implementation and calculation of anharmonic VCD rotational strengths
      for solvated systems is reported. Our approach, rooted in the polarizable
      continuum model (PCM) and in the second-order vibrational perturbation theory
      (VPT2), permits not only correction for anharmonicity in the signals associated
      with fundamental transitions but also calculation of rotational strengths of
      overtones and combination bands. This allows for a more physically consistent
      comparison between experiment and calculations together with the analysis of
      spectral regions dominated by anharmonic effects. The developed model is applied
      to a few test cases, and the computational outcomes are directly compared with
      experimental data. 

PMID- 26291858
TI  - Developing Plasmonics Under the Infrared Microscope: From Ni Nanoparticle Arrays
      to Infrared Micromesh.
AB  - Microscopes typically collect light over large ranges of angles dispersing
      plasmonic resonances. While this is an advantage for recording spectra of
      microscopic particles, it is a disadvantage for sensing by resonance shifts.
      Adaptations are described herein which enable one to identify, manipulate, and
      examine narrow plasmonic resonances under a microscope. Noting more general
      familiarity with metal nanoparticle arrays, a useful perspective is offered by
      relating the optical transmission of small Ni nanoparticle arrays to that of Ni
      metal films with microhole arrays, i.e., infrared-active mesh. This perspective
      also includes the connection to traditional dispersion studies, a new microscope
      method to measure the propagation length of surface-plasmon-polariton-mediated
      resonances, and the shifting of resonance positions by latex microspheres in the
      holes of mesh. A useful perspective is offered by relating the optical
      transmission of small Ni nanoparticle arrays to that of Ni metal films with
      microhole arrays, i.e., infrared-active mesh. 

PMID- 26291859
TI  - Nanoscale Fluorescence Imaging of Single Amyloid Fibrils.
AB  - Amyloid formation is implicated in a variety of human diseases. It is important
      to perform high-resolution optical imaging of individual amyloid fibrils to
      delineate the structural basis of supramolecular protein assembly. However,
      amyloid fibrils do not lend themselves to the conventional microscopic
      resolution, which is hindered by the diffraction limit. Here we show super
      resolution fluorescence imaging of fluorescently stained amyloid fibrils derived
      from disease-associated human beta2-microglobulin using near-field scanning
      fluorescence microscopy. Using this technique, we were able to resolve the
      fibrils that were spatially separated by ~75 nm. We have also been able to
      interrogate individual fibrils in a fibril-by-fibril manner by simultaneously
      monitoring both nanoscale topography and fluorescence brightness along the length
      of the fibrils. This method holds promise to detect conformational distributions
      and heterogeneity that are believed to correlate with the supramolecular packing
      of misfolded proteins within the fibrils in a diverse conformationally enciphered
      prion strains and amyloid polymorphs. 

PMID- 26291860
TI  - Biocompatible Xanthine-Quadruplex Scaffold for Ion-Transporting DNA Channels.
AB  - Molecular dynamics simulations and adaptive biasing force analysis of the
      quadruplex DNA dynamics in an explicit solvent reveal fundamentally different
      mechanisms of Na(+) transport in xanthine- and guanine-based DNA systems. The
      barrier to the transport of K(+) through the xanthine-based quadruplex is
      significantly lower than those reported for the guanine-based analogs. 

PMID- 26291861
TI  - Photothermal Response of Photoluminescent Silicon Nanocrystals.
AB  - We demonstrate that silicon nanocrystals (Si-NCs) exhibiting relatively high near
      IR photoluminescent quantum yields also exhibit a notable photothermal (PT)
      response. The PT effect has been quantified as a function of NC size, defect
      concentration, and irradiating energy, suggesting that the origin of the PT
      response is a combination of carrier thermalization and defect-mediated heating.
      The PT effect observed under NIR irradiation suggests that Si-NCs could find use
      in combined in vivo PL imaging and PT therapy. 

PMID- 26291862
TI  - Resolving the Electron Transfer Kinetics in the Bacterial Reaction Center by
      Pulse Polarized 2-D Photon Echo Spectroscopy.
AB  - At the heart of photosynthesis is excitation energy transfer toward and charge
      separation within highly conserved reaction centers (RCs). The function
      principles of RCs in purple bacteria offer a blueprint for an optoelectronic
      device, which efficiently utilizes the near-IR region of the solar spectrum. We
      present theoretical modeling of the nonlinear optical response of the bacterial
      RC B. viridis incorporating electron and energy transfer on equal footing. The
      splitting of special pair excitons P is the origin of distinct cross peaks, which
      allow monitoring of the kinetics of charge separation. The xxyy - xyxy signal,
      obtained from sequences of orthogonal polarized laser pulses, highlights the
      kinetics of the secondary, subpicosecond electron transfer from the accessory
      bacteriochlorophyll BClL to the bacteriopheophytine BPL. The increased
      selectivity is explained by the relative orientation of exciton transitions. The
      technique can resolve complex kinetics in congested signals of photosynthetic
      complexes that are otherwise hardly accessible. 

PMID- 26291863
TI  - Improved Sensing with Nanostructures.

PMID- 26291864
TI  - The Effect of the pi-Electron Delocalization Curvature on the Two-Photon Circular
      Dichroism of Molecules with Axial Chirality.
AB  - Herein we report on the theoretical-experimental study of the effect of curvature
      of the pi-electron delocalization on the two-photon circular dichroism (TPCD) of
      a family of optically active biaryl derivatives (S-BINOL, S-VANOL, and S-VAPOL).
      The comparative analysis of the influence of the different transition moments to
      their corresponding TPCD rotatory strength reveals an enhanced contribution of
      the magnetic transition dipole moment on VAPOL. This effect is hereby attributed
      to the additional twist in the pi-electron delocalization on this compound. TPCD
      measurements were done using the double L-scan technique in the picosecond
      regime. Theoretical calculations were completed using modern analytical response
      theory, within a time-dependent density functional theory (TD-DFT) approach, at
      both, B3LYP and CAM-B3LYP levels, with the aug-cc-pVDZ basis set for S-BINOL and
      S-VANOL, and 6-31G* for S-VAPOL. Solvent effects were included by means of the
      polarizable continuum model (PCM) in CH2Cl2. 

PMID- 26291865
TI  - Creating Long-Lived Spin States at Variable Magnetic Field by Means of
      Photochemically Induced Dynamic Nuclear Polarization.
AB  - We have shown that long-lived spin states (LLS) can be selectively populated by
      photogenerated chemically induced dynamic nuclear polarization (CIDNP) over a
      wide range of magnetic fields. Relaxation times of LLS of the beta-CH2 protons in
      N-acetyl histidine and partially deuterated histidine have been measured. Our
      experiments demonstrate that CIDNP enables creating LLS in the amino acid in a
      field range of up to a few Tesla and that their lifetimes can be 45 times longer
      than T1. The advantage of the method is thus two-fold: it allows one to
      accumulate high levels of spin hyperpolarization and to preserve them for periods
      of time far exceeding T1. Therefore, photo-CIDNP is a technique suitable for
      creating long-lived spin order in biologically relevant molecules. 

PMID- 26291866
TI  - Enhanced Vertical Concentration Gradient in Rubbed P3HT:PCBM Graded Bilayer Solar
      Cells.
AB  - Graded bilayer solar cells have proven to be at least as efficient as the bulk
      heterojunctions when it comes to the Poly(3-hexylthiophene) (P3HT) - [6,6]-phenyl
      C61-butyric acid methyl ester (PCBM) donor-acceptor system. However, control of
      the vertical concentration gradient using simple techniques has never been
      reported. We demonstrate that rubbing the P3HT layer prior to PCBM deposition
      induces major morphological changes in the active layer. Using the newly
      introduced energy-dispersive X-ray spectroscopy element mapping technique, we
      found that rubbing P3HT induces the formation of an ideal vertical donor-acceptor
      concentration gradient. Furthermore, the P3HT crystallites undergo a molecular
      reorientation from edge-on to face-on configuration inducing a better charge
      transport in the vertical direction. The combination of these two major
      morphological changes leads to the fabrication of high-performance solar cells
      that exhibit, to date, the record efficiencies for spin-coated graded bilayers
      solar cells. 

PMID- 26291867
TI  - Crumpled Graphene-Encapsulated Si Nanoparticles for Lithium Ion Battery Anodes.
AB  - Submicrometer-sized capsules made of Si nanoparticles wrapped by crumpled
      graphene shells were made by a rapid, one-step capillary-driven assembly route in
      aerosol droplets. Aqueous dispersion of micrometer-sized graphene oxide (GO)
      sheets and Si nanoparticles were nebulized to form aerosol droplets, which were
      passed through a preheated tube furnace. Evaporation-induced capillary force
      wrapped graphene (a.k.a., reduced GO) sheets around the Si particles, and heavily
      crumpled the shell. The folds and wrinkles in the crumpled graphene coating can
      accommodate the volume expansion of Si upon lithiation without fracture, and thus
      help to protect Si nanoparticles from excessive deposition of the insulating
      solid electrolyte interphase. Compared to the native Si particles, the composite
      capsules have greatly improved performance as Li ion battery anodes in terms of
      capacity, cycling stability, and Coulombic efficiency. 

PMID- 26291868
TI  - Design and Characterization of Heteroleptic Ruthenium Complexes Containing
      Benzimidazole Ligands for Dye-Sensitized Solar Cells: The Effect of Fluorine
      Substituents on Photovoltaic Performance.
AB  - We designed heteroleptic ruthenium complexes (RD12-RD15) containing fluoro
      substituted benzimidazole ligands for dye-sensitized solar cells (DSSCs). These
      dyes were synthesized according to a typical one-pot procedure with the
      corresponding ancillary ligands produced in two simple steps; they were prepared
      into DSSC devices according to the same conditions of fabrication. The eventual
      devices show a systematic trend of increasing VOC and decreasing JSC with
      fluorine atoms of increasing number substituted on the ligand. The charge
      extraction results show that upward shifts of the TiO2 potential occurred when
      the fluoro-substituted dyes were sensitized on TiO2 with a systematic trend of
      shift N719 > RD15 (with 5 F) > RD12 (with 2 F) >RD5 (no F); the intensity
      modulated photovoltage spectra indicate that those fluoro substituents retard
      charge recombination with the electron lifetimes (tauR) in the order RD15 > RD12
      > RD5 > N719, consistent with the variation of VOC for the systems. 

PMID- 26291869
TI  - Pushing the Sample-Size Limit of Infrared Vibrational Nanospectroscopy: From
      Monolayer toward Single Molecule Sensitivity.
AB  - While scattering-scanning near-field optical microscopy (s-SNOM) has demonstrated
      its potential to extend infrared (IR) spectroscopy into the nanometer scale, it
      has not yet reached its full potential in terms of spectroscopic sensitivity. We
      combine broadband femtosecond mid-IR excitation with an optimized spectral
      irradiance of ~2 W/cm(2)/ cm(-1) (power/area/bandwidth) and a combination of tip-
      and substrate enhancement to demonstrate single-monolayer sensitivity with
      exceptional signal-to-noise ratio. Using interferometric time domain detection,
      the near-field IR s-SNOM spectral phase directly reflects the molecular
      vibrational resonances and their intrinsic line shapes. We probe the stretching
      resonance of ~1000 carbonyl groups at 1700 cm(-1) in a self-assembled monolayer
      of 16-mercaptohexadecanoic acid (MHDA) on an evaporated gold substrate with
      spectroscopic contrast and sensitivity of ?100 vibrational oscillators. From
      these results we provide a roadmap for achieving true single-molecule IR
      vibrational spectroscopy in s-SNOM by implementing optical antenna resonant
      enhancement, increased spectral pump power, and improved detection schemes. 

PMID- 26291870
TI  - Monitoring Intramolecular Proton Transfer with Two-Dimensional Infrared
      Spectroscopy: A Computational Prediction.
AB  - Proton transfer processes are ubiquitous and play a vital role in a broad range
      of chemical and biochemical phenomena. The ability of two-dimensional infrared
      (2D IR) spectroscopy with a carbon-deuterium (C-D) reporter to monitor the
      kinetics of proton transfer in the model compound malonaldehyde was demonstrated
      computationally. One of the two carbonyl/enol carbon atoms in malonaldehyde was
      labeled with a C-D bond. The C-D stretch vibrational frequency provides ~150 cm(
      1) of sensitivity to the two tautomers of malonaldehyde. Mixed quantum
      mechanics/molecular mechanics simulations employing the self-consistent-charge
      density functional tight binding (SCC-DFTB) method were used to compute 2D IR
      line shapes for the C-D stretch of labeled malonaldehyde in aqueous solution. The
      2D IR spectra reveal cross peaks from the chemical exchange of the proton. The
      kinetics for the growth of the cross-peaks (and the decay of the diagonal peaks)
      precisely match the proton transfer rate observed in the SCC-DFTB simulations. 

PMID- 26291871
TI  - Long-Lived Electronic Coherence of Iodine in the Condensed Phase: Sharp Zero
      Phonon Lines in the B<->X Absorption and Emission of I2 in Solid Xe.
AB  - Our study of B<-X absorption of molecular iodine (I2) isolated in a low
      temperature crystalline xenon has revealed an exceptionally long-lived electronic
      coherence in condensed phase conditions. The visible absorption spectrum shows
      prominent vibronic structure in the form of zero-phonon lines (ZPLs) and phonon
      side bands (PSBs). The resolved spectrum implies weak interaction of the
      chromophore to the lattice degrees of freedom. The coherence extends past the
      vibrational period of the excited state molecule, unlike that observed in any
      condensed phase environment for I2 so far. The ZP transitions from the relaxing B
      state populations were resolved in the hot luminescence when the 532 nm laser was
      used for excitation. 

PMID- 26291872
TI  - Palladium-Catalyzed Trimethylenemethane Cycloaddition of Olefins Activated by the
      sigma-Electron-Withdrawing Trifluoromethyl Group.
AB  - alpha-Trifluoromethyl-styrenes, trifluoromethyl-enynes, and dienes undergo
      palladium-catalyzed trimethylenemethane cycloadditions under mild reaction
      conditions. The trifluoromethyl group serves as a unique sigma-electron
      withdrawing group for the activation of the olefin toward the cycloaddition. This
      method allows for the formation of exomethylene cyclopentanes bearing a
      quaternary center substituted by the trifluoromethyl group, compounds of interest
      for the pharmaceutical, agrochemical, and materials industries. In the diene
      series, the cycloaddition operates in a [3 + 4] and/or [3 + 2] manner to give
      rise to seven- and/or five-membered rings. This transformation greatly improves
      the scope of the TMM cycloaddition technology and provides invaluable insights
      into the reaction mechanism. 

PMID- 26291873
TI  - Gender-Related Differences in Outcomes on Acupuncture and Moxibustion Treatment
      Among Depression Patients.
AB  - OBJECTIVES: This study sought to (1) assess the effectiveness of acupuncture and
      moxibustion with a method of soothing the liver and regulating the mind on the
      quality of life among patients with depression and (2) study the sex differences
      of acupuncture and moxibustion in the treatment of depression on the basis of
      patient-reported outcomes. METHODS: In a single-blind, randomized, controlled
      trial conducted in Guangdong Province, China, in January and December 2010, 163
      patients who met the criteria for depression were enrolled. Eligible patients
      were allocated to three treatment groups (soothing liver and regulating mind
      group, acupoint shallow puncturing group, and non-acupoint shallow puncturing
      group). In all three groups, the treatment was given twice a week for 12 weeks.
      The Hamilton Depression Rating Scale (HAMD) and Symptom Checklist 90 (SCL90) were
      used to quantitatively assess patients before and 1 and 3 months after treatment.
      RESULTS: Non-statistically significant differences in the acupuncture and
      moxibustion therapeutic effects of soothing liver and regulating mind treatment
      were found between men and women (p>0.05). An item-by-item analysis of the SCL90
      and HAMD scores showed sex differences between the efficacy of the soothing liver
      and regulating mind group and the group receiving acupoint shallow puncturing.
      Women obtained lower scores in somatization, interpersonal relationship, anxiety,
      terror, and extremeness items and HAMD scores in the soothing liver and
      regulating mind group than in the acupoint shallow puncturing group (p<0.05),
      while men showed no significant differences between the soothing liver and
      regulating mind group and the acupoint shallow puncturing group (p>0.05).
      CONCLUSIONS: The therapeutic effect of soothing liver and regulating mind is
      similar for both sexes, but women were more sensitive to the efficacy of the
      soothing liver and regulating mind treatment compared with other methods. These
      findings could indicate an important issue to consider for the different
      acupuncture and moxibustion treatments for depression in men and women.

PMID- 26291874
TI  - The effect of cognitive load on hemispheric asymmetries in true and false memory.
AB  - Studies examining hemispheric asymmetries in false memory have shown that the
      right hemisphere (RH) is more susceptible to false memories compared to the left
      hemisphere (LH). Theories suggest that hemispheric asymmetries in true and false
      memory may be due to differences in representational coding and the use of top
      down mechanisms in each hemisphere. In the current study, the Deese-Roediger
      McDermott false memory paradigm was used in conjunction with divided visual field
      presentation to examine the role of top-down mechanisms in hemispheric
      asymmetries of true and false memory. In Experiment 1, participants studied lists
      of related words while completing secondary cognitive load tasks. In Experiment
      2, the secondary tasks were administered during memory retrieval instead of
      memory encoding. Results revealed that cognitive loads imposed during the study
      phase influenced veridical memory in the LH more than the RH, but cognitive loads
      imposed during retrieval did not influence veridical memory in either hemisphere.
      Surprisingly, false memory rates were not influenced by cognitive loads and were
      higher in the LH. These data provide evidence that, at least for veridical
      memory, top-down control mechanisms are used more readily for the encoding of
      information into memory in the LH compared to the RH.

PMID- 26291876
TI  - Solution processable, cross-linked sulfur polymers as solid electrolytes in dye
      sensitized solar cells.
AB  - Inverse-vulcanized polymeric sulfur has been prepared and utilized for solid
      state dye sensitized solar cells. A power conversion efficiency of 1.5% was
      recorded with a short-circuit current of 4.1 mA cm(-2) and an open-circuit
      voltage of 0.75 V under standard AM 1.5G illumination (1000 W m(-2)). The results
      in the present study qualify the new polymeric sulfur material as a future
      candidate as low-cost, hole-transport material for solid-state dye-sensitized
      solar cells. 

PMID- 26291875
TI  - Emerging Infections Program Efforts to Address Health Equity.
AB  - The Emerging Infections Program (EIP), a collaboration between (currently) 10
      state health departments, their academic center partners, and the Centers for
      Disease Control and Prevention, was established in 1995. The EIP performs active,
      population-based surveillance for important infectious diseases, addresses new
      problems as they arise, emphasizes projects that lead to prevention, and develops
      and evaluates public health practices. The EIP has increasingly addressed the
      health equity challenges posed by Healthy People 2020. These challenges include
      objectives to increase the proportion of Healthy People-specified conditions for
      which national data are available by race/ethnicity and socioeconomic status as a
      step toward first recognizing and subsequently eliminating health inequities. EIP
      has made substantial progress in moving from an initial focus on monitoring
      social determinants exclusively through collecting and analyzing data by
      race/ethnicity to identifying and piloting ways to conduct population-based
      surveillance by using area-based socioeconomic status measures. 

PMID- 26291877
TI  - Climate Change Sentiment on Twitter: An Unsolicited Public Opinion Poll.
AB  - The consequences of anthropogenic climate change are extensively debated through
      scientific papers, newspaper articles, and blogs. Newspaper articles may lack
      accuracy, while the severity of findings in scientific papers may be too opaque
      for the public to understand. Social media, however, is a forum where individuals
      of diverse backgrounds can share their thoughts and opinions. As consumption
      shifts from old media to new, Twitter has become a valuable resource for
      analyzing current events and headline news. In this research, we analyze tweets
      containing the word "climate" collected between September 2008 and July 2014.
      Through use of a previously developed sentiment measurement tool called the
      Hedonometer, we determine how collective sentiment varies in response to climate
      change news, events, and natural disasters. We find that natural disasters,
      climate bills, and oil-drilling can contribute to a decrease in happiness while
      climate rallies, a book release, and a green ideas contest can contribute to an
      increase in happiness. Words uncovered by our analysis suggest that responses to
      climate change news are predominately from climate change activists rather than
      climate change deniers, indicating that Twitter is a valuable resource for the
      spread of climate change awareness. 

PMID- 26291878
TI  - Re-Designing of Existing Pharmaceuticals for Environmental Biodegradability: A
      Tiered Approach with beta-Blocker Propranolol as an Example.
AB  - Worldwide, contamination of aquatic systems with micropollutants, including
      pharmaceuticals, is one of the challenges for sustainable management of water
      resources. Although micropollutants are present at low concentrations, many of
      them raise considerable toxicological concerns, particularly when present as
      components of complex mixtures. Recent research has shown that this problem
      cannot be sustainably solved with advanced effluent treatment. Therefore, an
      alternative that might overcome these environmental problems is the design of new
      pharmaceutical molecules or the redesign of existing pharmaceutical molecules
      that present the functionality needed for their application and have improved
      environmental biodegradability. Such redesigning can be performed by small
      molecular changes in the drug molecule with intact drug moiety which could
      incorporate the additional attribute such as biodegradability while retaining its
      pharmacological potency. This proof of concept study provides an approach for the
      rational redesign of a given pharmaceutical (Propranolol as an example). New
      derivatives with small molecular changes as compared to propranolol molecule were
      generated by a nontargeted photolysis process. Generated derivatives with intact
      drug moieties (an aromatic ring and a beta-ethanolamine moiety) were further
      screened for aerobic biodegradability and pharmacological potency. The
      feasibility of the approach of redesigning an existing pharmaceutical through
      nontargeted generation of new derivatives with intact drug moiety and through
      subsequent screening was demonstrated in this study. Application of such
      approaches in turn might contribute to the protection of water resources in a
      truly sustainable manner.

PMID- 26291879
TI  - Regio- and Stereoselective Synthesis of Spiropyrrolizidines and Piperazines
      through Azomethine Ylide Cycloaddition Reaction.
AB  - A series of original spiropyrrolizidine derivatives has been prepared by a one
      pot three-component [3 + 2] cycloaddition reaction of (E)-3-arylidene-1-phenyl
      pyrrolidine-2,5-diones, l-proline, and the cyclic ketones 1H-indole-2,3-dione
      (isatin), indenoquinoxaline-11-one and acenaphthenequinone. We disclose an
      unprecedented isomerization of some spiroadducts leading to a new family of
      spirooxindolepyrrolizidines. Furthermore, these cycloadducts underwent retro-1,3
      dipolar cycloaddition yielding unexpected regioisomers. Upon treatment of the
      dipolarophiles with in situ generated azomethine ylides from l-proline or
      acenaphthenequinone, formation of spiroadducts and unusual polycyclic fused
      piperazines through a stepwise [3 + 3] cycloaddition pathway is observed. The
      stereochemistry of these N-heterocycles has been confirmed by several X-ray
      diffraction studies. Some of these compounds exhibit extensive hydrogen bonding
      in the crystalline state. To enlighten the observed regio- and stereoselectivity
      of the [3 + 2] cycloaddition, calculations using the DFT approach at the B3LYP/6
      31G(d,p) level were carried out. It was found that this reaction is under kinetic
      control. 

PMID- 26291880
TI  - The consideration of indolicidin modification to balance its hemocompatibility
      and delivery efficiency.
AB  - Indolicidin (IL) is an antimicrobial peptide (AMP), which has been utilized as a
      cell penetrating peptide (CPP) for drug delivery. However, the hemolysis
      restricts its clinical application. Therefore, we investigated the delivery
      efficiency and hemocompatibility of IL and its derivatives. The transportation of
      fluorophore to NIH/3T3 cells could be improved either by in accompany with these
      peptides or in the form of peptide-conjugates. The hydrophobicity scales of these
      peptides were calculated according to their residues, which were compared to
      their effects on hemolysis as well as cell uptake efficiency. The results
      suggested that the cell penetrability of IL and its derivatives was related to
      their hydrophobicity scales based on the octanol-interface scale (DeltaGoct-if),
      whereas their hemolysis levels depended on the hydrophobicity scales based on
      interface (DeltaGwif). Consequently, we designed two peptides, IL-R57F89 and
      SAP10, to validate the correlation. These two peptides had similar DeltaGwif;
      however, the DeltaGoct-if of SAP10 was much higher than that of IL-K7F89. Both IL
      R57F89 and SAP10 demonstrated extremely low hemolysis. Compared to the limit cell
      uptake of SAP10, IL-R57F89 greatly promoted the delivery efficiency. These
      results were consistent to our prediction, suggesting that hydrophobicity scales
      should be a useful preliminary guidance for AMP-derived CPP design. 

PMID- 26291881
TI  - Submicron complex lipid carriers for curcumin delivery to intestinal epithelial
      cells: Effect of different emulsifiers on bioaccessibility and cell uptake.
AB  - Submicrometric lipid-based carriers were developed to encapsulate curcumin and
      deliver it to intestinal epithelial cells. A lipid matrix comprising monoolein,
      sunflower oil and water at weight ratio 1:1:1 was selected, upon screening of
      different combinations of amphiphilic molecules, vegetable oils and water,
      because of its high encapsulations efficiency of curcumin, retained over time and
      relatively lower content of amphiphilic molecules. Upon dispersion in aqueous
      phase, the carriers were stabilized by: (a) whey protein isolates (WPI), alone
      and (b) in combination with modified starch (WPI-MS), or by (c) polysorbate 20
      (T20). Whereas T20-stabilized systems exhibited extremely fine particles (120
      nm), WPI and WPI-MS stabilized carriers were characterized by a significantly
      larger mean particle size (270 nm). The thicker macromolecular layer of WPI and
      WPI-MS enabled better (a) physical stability, (b) controlled shell degradation
      during simulated digestion, and (c) curcumin bioaccessibility targeted at the
      intestinal digestion phase than T20-systems. However, uptake studies in HT29 cell
      lines, simulating intestinal epithelial cells, showed that WPI and WPI-MS
      carriers exhibited after 24h a lower relative uptake than T20-stabilized systems
      (about 60% and 80%, respectively), as a consequence of smaller size and higher
      cell adherence of T20 carriers to the cell membrane.

PMID- 26291882
TI  - iRhoms in the brain - a new frontier?

PMID- 26291884
TI  - Comparison of Retinal Nerve Fiber Layer Thickness in Terms of Birth Weight in
      Prematurely Born Children.
AB  - PURPOSE: To study the potential effects of both prematurity and the sub-groups of
      low birth weight on thickness of RNFL. METHODS: Prospective case series of 26
      preterm school-aged children with low birth weight whose retinal nerve fiber
      layer analyses with RTVue-100 Fourier-domain optic coherence tomography were
      performed in 2013 at the Department of Ophthalmology, Erzurum Region Education
      and Training Hospital. RESULTS: The mean retinal nerve fiber layer thicknesses
      were 100.6 +/- 13.3 microns in extremely low birth weight, 103.9 +/- 8.4 microns
      in very low birth weight, and 104.1 +/- 10.8 microns in low birth weight groups.
      There was no significant difference in RNFL among the groups. CONCLUSIONS: No
      significant relationship was found between birth weights and retinal nerve fiber
      layer thickness of preterm children who were appropriate for gestational age.

PMID- 26291883
TI  - Immunization of preterm infants.
AB  - Vaccinations of premature infants are often delayed despite being at an increased
      risk of contracting vaccine preventable diseases. This article reviews the
      current knowledge on the immune response to widely used vaccines, on the
      protection derived from routine immunization and on vaccine safety and
      tolerability in a population of preterm infants. Available data evaluating the
      immune response of preterm infants support early immunization without correction
      for gestational age. For a number of antigens, the antibody response to initial
      doses of vaccines may be lower than that of term infants, but protective
      concentrations are often achieved and memory successfully induced. Vaccines are
      immunogenic, safe and well tolerated in preterm infants. Preterm infants should
      be vaccinated using the same schedules as those usually recommended for full-term
      infants, with the exception of the hepatitis B vaccine, where additional doses
      should be administered in infants receiving the first dose during the first days
      of life if they weighed less than 2000 g because of a documented reduced immune
      response.

PMID- 26291885
TI  - Optimising a model-based approach to inferring fear learning from skin
      conductance responses.
AB  - Anticipatory sympathetic arousal is often inferred from skin conductance
      responses (SCR) and used to quantify fear learning. We have previously provided a
      model-based approach for this inference, based on a quantitative
      Psychophysiological Model (PsPM) formulated in non-linear dynamic equations. Here
      we seek to optimise the inversion of this PsPM. Using two independent fear
      conditioning datasets, we benchmark predictive validity as the sensitivity to
      separate the likely presence or absence of the unconditioned stimulus. Predictive
      validity is optimised across both datasets by (a) using a canonical form of the
      SCR shape (b) filtering the signal with a bi-directional band-pass filter with
      cut off frequencies 0.0159 and 5 Hz, (c) simultaneously inverting two trials (d)
      explicitly modelling skin conductance level changes between trials (e) the choice
      of the inversion algorithm (f) z-scoring estimates of anticipatory sympathetic
      arousal from each participant across trials. The original model-based method has
      higher predictive validity than conventional peak-scoring or an alternative model
      based method (Ledalab), and benefits from constraining the model, optimised data
      preconditioning, and post-processing of ensuing parameters.

PMID- 26291886
TI  - Recruitment of Contralateral Supplementary Motor Area in Functional Recovery
      Following Medial Frontal Lobe Surgery: An fMRI Case Study.
AB  - BACKGROUND AND OBJECTIVE: Supplementary motor area (SMA) syndrome, an executive
      disorder with motor and speech dysfunctions, is rather unpredictable with
      typically a complete or almost complete functional recovery within weeks or
      months. Compensatory mechanisms are associated with contralateral cortical
      recruitment of the lateral premotor circuitry. We sought to investigate the role
      of healthy SMA for motor recovery following surgery in the medial frontal lobe.
      METHODS: A 48-year-old right-handed man presented with focal motor seizures. The
      diagnostic work-up revealed a low-grade glioma at the superior frontal gyrus. The
      patient was operated on with intraoperative monitoring of motor pathways, and
      resection was taken to the functional boundaries. RESULTS: Postoperatively, the
      patient experienced a typical SMA syndrome that almost completely resolved in the
      long term. Motor recovery occurred concurrently with a shift of SMA activation to
      the healthy hemisphere together with an increased lateral premotor circuitry,
      especially for the hand map. CONCLUSION: Our results confirm brain remodeling of
      the lateral premotor cortex, as previously described, and indicate that
      functional improvement is also paralleled with a shift of SMA activation toward
      the healthy hemisphere.

PMID- 26291887
TI  - Subdural Hematoma and Oral Anticoagulation: A Therapeutic Dilemma from the
      Neurosurgical Point of View.
AB  - BACKGROUND: Oral anticoagulation is a common prophylactic therapy for several
      diseases with a high thromboembolic risk. Such medication harbors a possible
      hemorrhage risk, with a special risk for subdural hematoma (SDH). The safety and
      efficacy of resumption of oral anticoagulation versus long-term discontinuation
      has not been fully clarified in patients who experienced SDH while under
      treatment with oral anticoagulation. MATERIAL AND METHODS: We investigated the
      outcome of 49 patients who were identified retrospectively to have a SDH while
      receiving oral anticoagulation. RESULTS: Most bleeding occurred while patients
      were within the recommended therapeutic window for oral anticoagulation.
      Mortality was 15%. The event-free survival probability was higher in the group of
      patients with reinstitution of phenprocoumon therapy than in the group without.
      Over a median follow-up of 32 months, thromboembolic events occurred in 4 of 23
      patients without oral anticoagulation versus in none of 15 patients with
      phenprocoumon; hemorrhagic complications occurred in 1 in 23 versus 3 in 15
      patients. CONCLUSIONS: Reinstitution of oral anticoagulation with phenprocoumon
      after previous SDH appears to have an acceptable risk for hemorrhagic
      complications. Decision making might consider case-by-case differences. To
      establish specific guidelines, prospective large cohort studies are needed.

PMID- 26291888
TI  - Pathophysiology of Minimally Invasive Surgical Approaches: Current Concepts.
AB  - Spine surgery is a continuously evolving field. Traditional posterior midline
      approaches to the lumbar spine are associated with muscle injury. Common
      mechanisms of injury include ischemia, denervation, and mechanical disruption of
      tendinous attachments of lumbar muscles. Muscle injury may be documented with
      chemical markers (creatinine kinase, aldolase, proinflammatory cytokines), by
      imaging studies, or with muscle biopsy. Minimally disruptive surgical approaches
      to the spine have the potential to minimize the trauma to muscular structures and
      thus improve the outcomes of surgery. The impact of minimally invasive spinal
      surgery on long-term clinical outcomes remains unknown. State-of-the-art
      pathophysiology of minimally invasive spine surgery is presented in this review. 

PMID- 26291889
TI  - True Percutaneous Transforaminal Lumbar Interbody Fusion: Case Illustrations,
      Surgical Technique, and Limitations.
AB  - Objective The last decade has seen significant advances in minimally invasive
      techniques for lumbar interbody fusion that have reduced approach-related
      morbidity. Percutaneous lumbar interbody fusion involves a posterior
      transforaminal approach to the disk space with a minimal access port through the
      Kambin triangle. This technique obviates the need for the facetectomy or
      laminectomy required in a traditional transforaminal approach. This article
      describes the surgical technique, potential advantages and limitations, and
      representative case illustrations. Methods Percutaneous transforaminal interbody
      fusion was performed on two patients with axial back and leg pain as a result of
      degenerative disk disease. Diskectomy and interbody cage insertion were completed
      through a tubular dilator placed onto the disk space in the Kambin triangle.
      Posterior fixation was achieved with percutaneous transfacet screws. Clinical
      outcome and postoperative complications are discussed. Results Both patients
      demonstrated significant clinical improvement after surgery with > 1 year follow
      up despite experiencing transient neurologic symptoms. Conclusion Although this
      report demonstrates the feasibility and advantages of the approach, the technique
      is limited by the potential for nerve root injury and pseudoarthrosis. 

PMID- 26291890
TI  - Total syntheses of (-)-isoschizogamine and (-)-2-hydroxyisoschizogamine.
AB  - Total syntheses of (-)-isoschizogamine and (-)-2-hydroxyisoschizogamine are
      described. The synthesis employs two asymmetric Michael additions to establish
      chiral centers at C7 and the quaternary carbon C20. Regioselective reduction of
      the methylthioiminium cation rather than the enamine generates an isoschizogamine
      type pentacyclic skeleton. Acidic hydrolysis of the isoschizogamine-type
      intermediate in the absence of oxygen provides natural (-)-isoschizogamine.
      Conducting the reaction in the presence of oxygen leads to a multistep oxidative
      hydrolysis cascade that affords unnatural (-)-2-hydroxyisoschizogamine. 

PMID- 26291891
TI  - Mapping of functional domains and characterization of the transcription factor
      Cph1 that mediate morphogenesis in Candida albicans.
AB  - Cph1, a transcription factor of the Mitogen Activated Protein (MAP) kinase
      pathway, regulates morphogenesis in human fungal pathogen Candida albicans. Here,
      by following a systemic deletion approach, we have identified functional domains
      and motifs of Cph1 that are involved in transcription factor activity and
      cellular morphogenesis. We found that the N-terminal homeodomain is essential for
      the DNA binding activity; however, C-terminal domain and polyglutamine motif (PQ)
      are indispensable for the transcriptional activation function. Complementation
      analysis of the cph1Delta null mutant using various deletion derivatives revealed
      functional significance of the N- and C-terminal domains and PQ motif in
      filamentation process, chlamydospore formation and sensitivity to the cell wall
      interfering compounds. Genome-wide identification of the Cph1 binding site and
      quantitative RT-PCR transcript analysis in cph1Delta null mutant revealed that a
      number of genes which are associated with the filamentous growth, maintaining
      cell wall organization and mitochondrial function, and the genes of the pH
      response pathway are the transcriptional targets of Cph1. The data also suggest
      that Cph1 may function as a positive or negative regulator depending on the
      morphological state and physiological conditions. Moreover, differential
      expression of the upstream MAP kinase pathway genes in wild type and cph1Delta
      null mutant indicated the existence of a feedback regulation. 

PMID- 26291892
TI  - Investigations into the Immunotoxicity and Allergic Potential Induced by Topical
      Application of N-Butylbenzenesulfonamide (NBBS) in a Murine Model.
AB  - N-Butylbenzene sulfonamide (NBBS) is a commonly used plasticizer found in
      numerous products. Due to its extensive use, lack of adequate toxicological data,
      and suspicion of toxicity based on the presence of structural alerts, it was
      nominated to the National Toxicology Program for comprehensive toxicological
      testing. The purpose of this study was to evaluate the potential for
      hypersensitivity and immune suppression following dermal exposure to NBBS using a
      murine model. NBBS tested negative in a combined irritancy/local lymph node assay
      (LLNA), classifying it as nonirritating and nonsensitizing. To estimate the
      immunosuppressive potential of NBBS, assays that assessed immunotoxicity were
      performed, including the immumnoglobulin (Ig) M response to T-cell-dependent
      antigen sheep red blood cells (SRBC), using the plaque-forming cell (PFC) assay
      and immune cell phenotyping. After a 28-d treatment with NBBS, mice exposed to
      the lowest concentration (25% NBBS) showed a significant increase in IgM
      producing B cells in the spleen. No marked changes were identified in immune cell
      markers in the lymph node. In contrast to body weight, a significant elevation in
      kidney and liver weight was observed following dermal exposure to all
      concentrations of NBBS. These results demonstrate that dermal exposure to NBBS,
      other than liver and kidney toxicity, did not apparently induce immunotoxicity in
      a murine model. 

PMID- 26291893
TI  - The ADAM33 S2 polymorphism is associated with susceptibility to pediatric asthma
      in the Chinese Han population.
AB  - BACKGROUND: The disintegrin and metalloprotease domain containing protein 33
      (ADAM33) is a novel susceptibility gene for asthma and airway
      hyperresponsiveness, particularly in the Asian population. We investigated the
      influence of ADAM33 polymorphisms on the serum levels of ADAM33 and the
      susceptibility to pediatric asthma in the Chinese Han population. METHODS:
      Polymerase chain reaction-restriction fragment length polymorphism analysis was
      employed to study the genotypic distribution of F+1, T1, and S2 in ADAM33 in a
      cohort of 120 pediatric asthma patients and 105 healthy controls. The serum
      levels of secreted ADAM33 protein were measured in all the study subjects using
      the enzyme-linked immunosorbent assay (ELISA). RESULTS: This case-control study
      showed that the distribution of F+1 and T1 genotypes of ADAM33 was not
      significantly different between pediatric asthma patients and healthy controls (p
      > 0.05); however, the genotype and allele frequencies of the S2 polymorphism were
      significantly different between asthmatic patients and healthy controls (both p <
      0.05). In addition, the frequency of CGC and CGG haplotypes exhibited
      statistically significant differences, with lower CGC and higher CGG frequencies
      found in the case group compared to the control group. Finally, in comparison to
      healthy controls, the serum levels of ADAM33 protein were significantly lower in
      patients carrying the S2 polymorphism. CONCLUSION: Our results provide evidence
      that the ADAM33 S2 polymorphism is associated with increased susceptibility to
      pediatric asthma and that the CGG haplotype for the F+1, T1, and S2 polymorphisms
      is associated with an elevated risk of pediatric asthma in the Han population,
      whereas the CGC haplotype appears to confer a protective effect. Our results may
      prove useful for population-based screening to affect early intervention.

PMID- 26291894
TI  - The Trans-Pacific Partnership Agreement and Implications for Access to Essential
      Medicines.

PMID- 26291895
TI  - Editorial Opinion: Please Don't Take My AHRQ Away.

PMID- 26291897
TI  - An In vivo Wound Model Utilizing Bacteriophage Therapy of Pseudomonas aeruginosa
      Biofilms.
AB  - Bacteriophages have been used as effective therapy against bacterial biofilms on
      devices such as catheters, in the lungs such as in cystic fibrosis, and even in
      infected food. Unlike antibiotics, they are bacteria-specific and produce the
      desired effect without systemic complications; they can develop bacterial
      resistance, although in ways different from antibiotics. The present study aimed
      to assess the effect of bacteriophages against multidrug-resistant Pseudomonas
      aeruginosa in a mouse wound model. P. aeruginosa obtained from laboratory culture
      of burn wounds were characterized, harvested, and titrated, and biofilms were
      generated on sterile catheter sections (105 colony forming units/mL).
      Subcutaneous pockets were created on the backs of 24 male albino mice. Animals
      were randomized into 4 groups of 6 each. After evaluating a significant phage
      bacteria interaction in vitro, 2 biofilm-laden catheter sections were implanted
      in subcutaneous pockets in mouse groups C and D. Sterile catheter sections only
      were implanted in group B. Group A had only a subcutaneous pocket without any
      catheter section. Phage cocktail solutions (10 ?'b5L of 107 phage forming
      units/mL) were injected daily in group D pockets only. Groups B and C received 10
      ?'b5L of normal saline. After 10 days, the catheter sections were explanted from
      groups B, C, and D and tissue biopsy was taken from group A pockets and cultured
      for bacterial and phage colony counts. A significant drop in bacterial counts
      from 3.87 x 106 to 3.52 x 104 was observed in group D when compared with group C
      (3.87 x 106 to 3.85 x 105, P less than 0.05) A significant rise in the phage
      counts from 1 x 107 to 6.81 x 108 (P less than 0.05) also was observed in group D
      when compared with the baseline counts, indicating active phage proliferation and
      successful bacterial kill in group D. The present laboratory study could be
      indicative of a new treatment approach for multidrug-resistant bacterial
      infections, including wound infections. 

PMID- 26291898
TI  - Assessing the Validity and Reliability of the Peristomal Skin Lesion Assessment
      Instrument Adapted for Use in Turkey.
AB  - Many ostomy patients experience peristomal skin lesions. A descriptive study was
      conducted to assess the validity, usability, and reliability of the Peristomal
      Skin Lesions Assessment instrument (SACS instrument) adapted to Turkish from
      English. The SACS Instrument consists of 2 main assessments: lesion type
      (utilizing definitions and photographs) and lesion area by location around the
      ostomy. The study was performed in 2 stages: 1) the SACS language was changed and
      its content validity established; and 2) the instrument?'92s content validity and
      inter-observer agreement (consistency) were determined among pairs of nurses who
      used the tool to assess peristomal skin lesions. Patients (included if they were
      >18 years old and receiving treatment/observation at 1 of the 4 participating
      stomatherapy units) and 8 stomatherapy nurses also completed appropriate
      sociodemographic questionnaires. Of the 393 patients screened during the 7-month
      study, 100 (average age 56.74 ?'b1 14.03 years, 55 men) participated; most (79)
      had a planned operation. A little more than half (59) of the patients had
      colorectal cancer and 28 had their stoma site marked preoperatively by a
      stomatherapy nurse. The most common peristomal skin lesion risk factors were
      having an ileostomy and unplanned surgery. The content validity index of the
      entire Turkish SACS instrument was 1, and the inter-observer agreement Kappa
      statistic was very good (K = 0.90, 95% CI 0.80- 0.99). Individual SACS item K
      values ranged from K = 0.84 (95% CI 0.63?'961) to K = 1 (95% CI 1). Most (62.5%)
      nurses found the terms and pictures used in the SACS classification adequate and
      suitable, and 50% believed the Turkish version of the SACS instrument was a valid
      and suitable assessment tool for use by Turkish stomatherapy nurses. Validity and
      reliability studies involving larger and more diverse patient and nurse samples
      are warranted. 

PMID- 26291899
TI  - A Skin-stretching Wound Closure System to Prevent and Manage Dehiscence of High
      tension Flap Donor Sites: A Report of 2 Cases.
AB  - Tension on the suture line of flap donor sites raises the risk of delayed healing
      and wound dehiscence. Closing a large flap donor site without a skin/flap graft
      is a major surgical challenge. Recently, the authors started using a skin
      stretching wound closure system designed to harness both mechanical creep and
      stress-relaxation principles for the management of a variety of surgically closed
      wounds, including flap donor sites. The system consists of a pair of attachment
      plates connected by a long, flexible approximation strap that can be invasively
      (sutured) or noninvasively (by adhesion) secured to the skin wound edges and
      gradually tightened. The care and outcomes of 2 of the 41 patients whose wounds
      were managed with this system at the authors?'92 plastic/reconstructive and wound
      repair center during a period of 7 months are described. The first case involved
      a 20-year-old patient with a 16 cm x 8 cm deep inferior epigastric perforator
      flap to reconstruct a malignant tumor resection of the groin. The second patient
      required a 10 cm x 8 cm anterolateral thigh free-flap to repair a traumatic
      dorsal skin, soft tissue defect. Wounds were assessed and tension adjusted every
      2 or 3 days. Both lesions healed by primary intention and with a good cosmetic
      outcome. Controlled clinical studies are needed to examine the effectiveness,
      efficacy, indications, complications, and cost effectiveness of this closure
      system. 

PMID- 26291900
TI  - Targeted Fluid Minimization Following Initial Resuscitation in Septic Shock: A
      Pilot Study.
AB  - BACKGROUND: IV fluid represents a basic therapeutic intervention for septic
      shock. Unfortunately, the optimal administration of IV fluid to maximize patient
      outcomes and prevent complications is largely unknown. METHODS: Patients with
      septic shock admitted to the medical ICUs of Barnes-Jewish Hospital (January to
      December 2014) requiring vasoactive agents for at least 12 h following initial
      fluid resuscitation were randomized to usual care or to targeted fluid
      minimization (TFM) guided by daily assessments of fluid responsiveness. RESULTS:
      Eighty-two patients were enrolled, 41 to usual care and 41 to TFM. For patients
      randomized to TFM, the net median (interquartile range) fluid balance was less at
      the end of day 3 (1,952 mL [48-5,003 mL] vs 3,124 mL [767-10,103 mL], P = .20)
      and at the end of day 5 (2,641 mL [-1,837 to 5,075 mL] vs 3,616 mL [ -1,513 mL to
      9,746 mL], P = .40). TFM appeared to be safe, as indicated by similar clinical
      outcomes including in-hospital mortality (56.1% vs 48.8%, P = .51), ventilator
      days (8.0 days [3.25-15.25 days] vs 5.0 days [3.0-9.0 days], P = .30), renal
      replacement therapy (41.5% vs 39.0%, P = .82), and vasopressor days (4.0 days
      [2.0-8.0 days] vs 4.0 days [2.0-6.0 days], P = .84). CONCLUSIONS: This pilot
      study suggests that TFM in patients with septic shock can be performed using
      protocol-guided assessments of fluid responsiveness. Larger trials of TFM in
      septic shock are needed. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02473718;
      URL: www.clinicaltrials.gov.

PMID- 26291901
TI  - Pathogens, Metabolic Adaptation, and Human Diseases--An Iron-Thrifty Genetic
      Model.

PMID- 26291902
TI  - AV Block on Exertion: Pulmonary Sarcoidosis with Involvement of the His-Purkinje
      System.

PMID- 26291904
TI  - Disease and Poverty Go Hand in Hand in America.

PMID- 26291903
TI  - Transient Unilateral Neck Swelling After Unusual Exertion.

PMID- 26291905
TI  - Azithromycin for the Prevention of COPD Exacerbations: The Good, Bad, and Ugly.
AB  - Long-term azithromycin therapy has been shown to reduce exacerbations of chronic
      obstructive pulmonary disease (COPD), and is recommended by recent society
      guidelines for use in COPD patients who are at risk for recurrent exacerbations.
      However, concerns about adverse effects have limited its widespread adoption.
      Physicians deciding whether to use long-term azithromycin therapy must weigh each
      patient's individual risk of cardiovascular complications and both the individual
      and population impact of macrolide resistance against the expected benefit. This
      review will summarize evidence on the effectiveness and safety of chronic
      azithromycin for the prevention of COPD exacerbations. 

PMID- 26291906
TI  - Reflections on the Physicians Payment Sunshine Act.

PMID- 26291907
TI  - Chronic Mesenteric Ischemia: A Rare Cause of Chronic Abdominal Pain.
AB  - BACKGROUND: Chronic mesenteric ischemia is a rare disease with nonspecific
      clinical symptoms, such as chronic postprandial abdominal pain and weight loss.
      Diagnostic modalities and revascularization techniques have evolved during the
      past 20 years. The significance of stenosis in a single splanchnic vessel remains
      unclear. Our aims were to assess the outcomes of 2 revascularization techniques
      and report on the diagnostic modalities of splanchnic vessel stenoses. METHODS:
      The demographic data, medical history, technical characteristics, and outcomes of
      the revascularization procedures were recorded for all of the patients admitted
      for endovascular revascularization or open surgical revascularization of the
      splanchnic vessels as treatment for chronic mesenteric ischemia in our tertiary
      referral center since 2000. RESULTS: Fifty-four patients were included in this
      study: 43 received endovascular revascularization, and 11 had open surgical
      revascularization. The symptoms were abdominal pain, weight loss, and diarrhea in
      98%, 53%, and 25% of the cases, respectively. Computed tomography angiography was
      the key diagnostic tool for 60% of the patients. A single-vessel stenosis was
      found in one-third of the patients. Endovascular and open revascularization had
      similar early and late outcomes, and no 30-day mortality was observed. However,
      we did observe higher morbidity in the open revascularization group (73% vs 19%,
      P <.03). CONCLUSIONS: Chronic mesenteric ischemia may be diagnosed in the
      presence of a splanchnic syndrome and stenosis of a single splanchnic vessel,
      typically assessed using computed tomography angiography. In selected patients,
      endovascular revascularization had similar efficacy as, and lower complication
      rates than open revascularization.

PMID- 26291908
TI  - Mobile Menace: Floating Aortic Arch Thrombus.

PMID- 26291909
TI  - Diagnosing Beethoven: A New Take on an Old Patient.

PMID- 26291910
TI  - Electrochemical mineralization of the antibiotic levofloxacin by electro-Fenton
      pyrite process.
AB  - Levofloxacin is a large spectrum antibiotic from fluoroquinolones family, widely
      used and detected in natural waters. Here, this drug was degraded by a novel
      heterogeneous electro-Fenton (EF) process, so-called EF-pyrite, in which pyrite
      powder in suspension regulates the solution pH to 3.0 and supplies 0.2mM Fe(2+)
      as catalyst to the solution. Trials were performed with a stirred boron-doped
      diamond (BDD)/carbon-felt cell under O2 bubbling for cathodic H2O2 generation.
      Hydroxyl radicals formed from water oxidation at the BDD anode and in the bulk
      from Fenton's reaction between Fe(2+) and H2O2 were the main oxidizing agents.
      The effect of applied current and antibiotic concentration over the
      mineralization rate and degree, mineralization current efficiency and specific
      energy consumption was studied. An almost total mineralization was achieved for a
      0.23mM drug solution operating at 300mA for 8h. The kinetic decay of the drug was
      followed by reversed-phase HPLC and obeyed a pseudo-first-order reaction. Ion
      exclusion HPLC analysis of treated solutions revealed that oxalic and oxamic
      acids, the most persistent final products, were the predominant pollutants
      remaining in solution at long electrolysis time. Ion chromatography analysis
      confirmed the release of F(-), NO3(-) and NH4(+) ions during levofloxacin
      mineralization. 

PMID- 26291911
TI  - Rapid degradation of aniline in aqueous solution by ozone in the presence of zero
      valent zinc.
AB  - The effects of Zn(0) dosage from 0.1 to 1.3gL(-1), pH from 2 to 12 and
      temperature from 288 to 318K on the degradation of aniline in aqueous solution by
      ozone in the presence of Zn(0) were investigated through batch experiments. The
      results demonstrated that Zn(0) had a significantly synergistic role in the
      degradation of aniline by ozone. A complete decomposition of the initial aniline
      (10mgL(-1)) was achieved by ozone together with Zn(0) within 25min, and meanwhile
      nearly 70% of the total organic carbon in the solution was removed. The
      decomposition efficiency of aniline markedly increased with an increase of Zn(0)
      dosage. However, temperature exerted a slight impact on the degradation of
      aniline and the optimum removal efficiency of aniline was realized at 298K.
      Aniline was efficiently degraded at all the tested pHs except for 12. Free
      radicals were investigated by electron paramagnetic resonance technique and free
      radical scavengers. H2O2 concentration generated during the reactions was
      analyzed using a photometric method. Based on the results obtained in this study,
      it is proposed that O2(-) instead of OH is the dominant active species
      responsible for the degradation of aniline. It is concluded that ozone combined
      with Zn(0) is an effective and promising approach to the degradation of organic
      pollutants. 

PMID- 26291912
TI  - Removing PAHs from urban runoff water by combining ozonation and carbon nano
      onions.
AB  - Ozone (O3) is a chemical oxidant capable of transforming polycyclic aromatic
      hydrocarbons (PAHs) in urban runoff within minutes but complete oxidation to CO2
      can take days to weeks. We developed and tested a flow-through system that used
      ozone to quickly transform PAHs in a runoff stream and then removed the ozone
      transformed PAHs via adsorption to carbon nano-onions (CNOs). To quantify the
      efficacy of this approach, (14)C-labeled phenanthrene and benzo(a)pyrene, as well
      as a mixture of 16 unlabeled PAHs were used as test compounds. These PAHs were
      pumped from a reservoir into a flow-through reactor that continuously ozonated
      the solution. Outflow from the reactor then went to a chamber that contained CNOs
      to adsorb the ozone-transformed PAHs and allowed clean water to pass. By adding a
      microbial consortium to the CNOs following adsorption, we observed that bacteria
      were able to degrade the adsorbed products and release more soluble,
      biodegradable products back into solution. Control treatments confirmed that
      parent PAH structures (i.e., non-ozonated) were not biologically degraded
      following CNO adsorption and that O3-transformed PAHs were not released from the
      CNOs in the absence of bacteria. These results support the combined use of ozone,
      carbon nano-onions with subsequent biological degradation as a means of removing
      PAHs from urban runoff or a commercial waste stream. 

PMID- 26291913
TI  - Production of a bioflocculant from methanol wastewater and its application in
      arsenite removal.
AB  - A novel bioflocculant (MBF83) prepared using methanol wastewater as nutrient
      resource was systematically investigated in the study. The optimal conditions for
      bioflocculant production were determined to be an inoculum size of 8.6%, initial
      pH of 7.5, and a methanol concentration of 100.8mgL(-1). An MBF83 of 4.61gL(-1)
      was achieved as the maximum yield. MBF83 primarily comprised polysaccharide
      (74.1%) and protein (24.2%). The biopolymer, which was found to be safe in
      zebrafish in toxicity studies, was characterized using Fourier-transform infrared
      spectroscopy and elemental analysis. Additionally, conditions for the removal of
      arsenite by MBF83 were found to be MBF83 at 500mgL(-1), an initial pH of 7.0, and
      a contact time of 90min. Under the optimal conditions, the removal efficiency of
      arsenite was 86.1%. Overall, these findings indicate bioflocculation offers an
      effective alternative method of decreasing arsenite during wastewater treatment. 

PMID- 26291915
TI  - The atmospheric oxidation mechanism of 2-methylnaphthalene.
AB  - The atmospheric oxidation mechanism of 2-methylnaphthalene (2-MN) initiated by OH
      radicals is investigated by using quantum chemistry at BH&HLYP/6-311++G(2df,2p)
      and ROCBS-QB3 levels and kinetic calculations by transient state theory and
      unimolecular reaction theory coupled with master equation (RRKM-ME). This
      reaction is mainly initiated by OH additions, forming adducts Rn (2-MN-n-OH, n =
      1-8). The fates of R1 and R3, representing the alpha- and beta-adducts, are
      examined. The fates of R1 and R3 are found to be drastically different. In the
      atmosphere, R1 reacts with O2via O2 addition to the C2 position to form R1-2OO
      a/s, which will undergo a bimolecular reaction with the atmospheric NO or
      unimolecular isomerization via intramolecular H-shifts, of which the latter is
      found to be dominant and accounts for the formation of dicarbonyl compounds
      observed in experimental studies. The role of the tricyclic radical intermediates
      formed from the ring-closure of R1-2OO is rather limited because their formation
      is endothermic and reversible, being contrary to the important role of the
      analogous bicyclic radical intermediates in the oxidation of benzenes. On the
      other hand, the fate of R3 is similar to that of the benzene-OH adduct, and the
      tricyclic intermediates will play an important role. An oxidation mechanism is
      proposed based on the theoretical predictions, and the routes for the
      experimentally observed products are suggested and compared. 

PMID- 26291914
TI  - Chlorination of tramadol: Reaction kinetics, mechanism and genotoxicity
      evaluation.
AB  - Tramadol (TRA) is one of the most detected analgesics in environmental matrices,
      and it is of high significance to study the reactivity of TRA during chlorination
      considering its potential toxicity to the environment. The chlorine/TRA reaction
      is first order with respect to the TRA concentration, and a combination of first
      order and second-order with respect to chlorine concentration. The pH dependence
      of the observed rate constants (kobs) showed that the TRA oxidation reactivity
      increased with increasing pH. kobs can be quantitatively described by considering
      all active species including Cl2, Cl2O and HOCl, and the individual rate
      constants of HOCl/TRA(0), HOCl/TRAH(+), Cl2/TRA and Cl2O/TRA reactions were
      calculated to be (2.61+/-0.29)*10(3)M(-1)s(-1), 14.73+/-4.17M(-1)s(-1), (3.93+/
      0.34)*10(5)M(-1)s(-1) and (5.66+/-1.83)*10(6)M(-1)s(-1), respectively. Eleven
      degradation products were detected with UPLC-Q-TOF-MS, and the corresponding
      structures of eight products found under various pH conditions were proposed. The
      amine group was proposed to be the initial attack site under alkaline pH
      conditions, where reaction of the deprotonated amine group with HOCl is
      favorable. Under acidic and neutral pH conditions, however, two possible reaction
      pathways were proposed. One is an electrophilic substitution on the aromatic
      ring, and another is an electrophilic substitution on the nitrogen, leading to an
      N-chlorinated intermediate, which can be further oxidized. Finally, the SOS/umu
      test showed that the genotoxicity of TRA chlorination products increased with
      increasing dosage of chlorine, which was mostly attributed to the formation of
      some chlorine substitution products. 

PMID- 26291916
TI  - Innovative methods for parents and clinics to create tools for kids' care
      (IMPACCT Kids' Care) study protocol.
AB  - BACKGROUND: Despite expansions in public health insurance, many children remain
      uninsured or experience gaps in coverage. Community health centers (CHCs) provide
      primary care to many children at risk for uninsurance and are well-positioned to
      help families obtain and retain children's coverage. Recent advances in health
      information technology (HIT) capabilities provide the means to create tools that
      could enhance CHCs' insurance outreach efforts. OBJECTIVE: To present the study
      design, baseline patient characteristics, variables, and statistical methods for
      the Innovative Methods for Parents And Clinics to Create Tools for Kids' Care
      (IMPACCT Kids' Care) study. METHODS/DESIGN: In this mixed methods study, we will
      design, test and refine health insurance outreach HIT tools through a user
      centered process. We will then implement the tools in four CHCs and evaluate
      their effectiveness and barriers and facilitators to their implementation. To
      measure effectiveness, we will quantitatively assess health insurance coverage
      continuity and utilization of healthcare services for pediatric patients in
      intervention CHCs compared to matched control sites using electronic health
      record (EHR) and Oregon Medicaid administrative data over 18months pre- and
      18months post-implementation (n=34,867 children). We will also qualitatively
      assess the implementation process to understand how the tools fit into the
      clinics' workflows and the CHC staff experiences with the tools. CONCLUSIONS:
      This study creates, implements, and evaluates health insurance outreach HIT
      tools. The use of such tools will likely improve care delivery and health
      outcomes, reduce healthcare disparities for vulnerable populations, and enhance
      overall healthcare system performance. ClinicalTrials.gov Identifier:
      NCT02298361.

PMID- 26291917
TI  - Controlling anal incontinence in women by performing anal exercises with
      biofeedback or loperamide (CAPABLe) trial: Design and methods.
AB  - The goals of this trial are to determine the efficacy and safety of two
      treatments for women experiencing fecal incontinence. First, we aim to compare
      the use of loperamide to placebo and second, to compare the use of anal sphincter
      exercises with biofeedback to usual care. The primary outcome is the change from
      baseline in the St. Mark's (Vaizey) Score 24weeks after treatment initiation. As
      a Pelvic Floor Disorders Network (PFDN) trial, subjects are enrolling from eight
      PFDN clinical centers across the United States. A centralized data coordinating
      center supervises data collection and analysis. These two first-line treatments
      for fecal incontinence are being investigated simultaneously using a two-by-two
      randomized factorial design: a medication intervention (loperamide versus
      placebo) and a pelvic floor strength and sensory training intervention (anal
      sphincter exercises with manometry-assisted biofeedback versus usual care using
      an educational pamphlet). Interventionists providing the anal sphincter exercise
      training with biofeedback have received standardized training and assessment.
      Symptom severity, diary, standardized anorectal manometry and health-related
      quality of life outcomes are assessed using validated instruments administered by
      researchers masked to randomized interventions. Cost effectiveness analyses will
      be performed using prospectively collected data on care costs and resource
      utilization. This article describes the rationale and design of this randomized
      trial, focusing on specific research concepts of interest to researchers in the
      field of female pelvic floor disorders and all other providers who care for
      patients with fecal incontinence.

PMID- 26291918
TI  - Serum levels of sex steroids and metabolites following 12 weeks of intravaginal
      0.50% DHEA administration.
AB  - The objective of the present phase III, placebo-controlled, double-blind,
      prospective and randomized study was to confirm the efficacy of daily
      intravaginal administration of 0.50% dehydroepiandrosterone (DHEA; prasterone)
      ovules for 12 weeks on moderate to severe dyspareunia (or pain at sexual
      activity) as most bothersome symptom of vulvovaginal atrophy (VVA) while having
      serum steroid concentrations within normal postmenopausal values. To this end,
      serum levels of DHEA, DHEA-sulfate (DHEA-S), Androst-5-ene-diol-3beta, 17beta
      diol (5-diol), testosterone, dihydrotestosterone (DHT), androstenedione (4
      dione), estrone (E1), estradiol (E2), estrone sulfate (E1-S), androsterone
      glucuronide (ADT-G), and androstane-3alpha, 17beta-diol 17-glucuronide (3alpha
      diol-17G) were measured by validated liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). In agreement with the mechanisms of intracrinology, all
      serum sex steroids and metabolites concentrations after 12 weeks of daily
      intravaginal administration of 0.50% DHEA remain well within the limits of normal
      postmenopausal women. More specifically, the 12-week serum E2 concentration was
      measured at 22% below the average normal postmenopausal value (3.26 versus 4.17
      pg/ml), thus eliminating any fear of E2 exposure outside the vagina. In addition,
      serum E1-S, a particularly reliable indicator of global estrogenic activity,
      shows serum levels practically superimposable to the value observed in normal
      postmenopausal women (219 versus 220 pg/ml). Similarly, serum ADT-G, the major
      metabolite of androgens, remains within normal postmenopausal values. The present
      data confirm the intracellular transformation of DHEA in the vagina resulting in
      local efficacy without any systemic exposure to sex steroids, observations which
      are in agreement with the physiological mechanisms of menopause.

PMID- 26291919
TI  - Arbuscular mycorrhizal symbiosis ameliorates the optimum quantum yield of
      photosystem II and reduces non-photochemical quenching in rice plants subjected
      to salt stress.
AB  - Rice is the most important food crop in the world and is a primary source of food
      for more than half of the world population. However, salinity is considered the
      most common abiotic stress reducing its productivity. Soil salinity inhibits
      photosynthetic processes, which can induce an over-reduction of the reaction
      centres in photosystem II (PSII), damaging the photosynthetic machinery. The
      arbuscular mycorrhizal (AM) symbiosis may improve host plant tolerance to
      salinity, but it is not clear how the AM symbiosis affects the plant
      photosynthetic capacity, particularly the efficiency of PSII. This study aimed at
      determining the influence of the AM symbiosis on the performance of PSII in rice
      plants subjected to salinity. Photosynthetic activity, plant gas-exchange
      parameters, accumulation of photosynthetic pigments and rubisco activity and gene
      expression were also measured in order to analyse comprehensively the response of
      the photosynthetic processes to AM symbiosis and salinity. Results showed that
      the AM symbiosis enhanced the actual quantum yield of PSII photochemistry and
      reduced the quantum yield of non-photochemical quenching in rice plants subjected
      to salinity. AM rice plants maintained higher net photosynthetic rate, stomatal
      conductance and transpiration rate than nonAM plants. Thus, we propose that AM
      rice plants had a higher photochemical efficiency for CO2 fixation and solar
      energy utilization and this increases plant salt tolerance by preventing the
      injury to the photosystems reaction centres and by allowing a better utilization
      of light energy in photochemical processes. All these processes translated into
      higher photosynthetic and rubisco activities in AM rice plants and improved plant
      biomass production under salinity. 

PMID- 26291920
TI  - Assessing the safety effects of multiple roadside treatments using parametric and
      nonparametric approaches.
AB  - This study evaluates the safety effectiveness of multiple roadside elements on
      roadway segments by estimating crash modification factors (CMFs) using the cross
      sectional method. To consider the nonlinearity in crash predictors, the study
      develops generalized nonlinear models (GNMs) and multivariate adaptive regression
      splines (MARS) models. The MARS is one of the promising data mining techniques
      due to its ability to consider the interaction impact of more than one variables
      and nonlinearity of predictors simultaneously. The CMFs were developed for four
      roadside elements (driveway density, poles density, distance to poles, and
      distance to trees) and combined safety effects of multiple treatments were
      interpreted by the interaction terms from the MARS models. Five years of crash
      data from 2008 to 2012 were collected for rural undivided four-lane roadways in
      Florida for different crash types and severity levels. The results show that the
      safety effects decrease as density of driveways and roadside poles increase. The
      estimated CMFs also indicate that increasing distance to roadside poles and trees
      reduces crashes. The study demonstrates that the GNMs show slightly better model
      fitness than negative binomial (NB) models. Moreover, the MARS models
      outperformed NB and GNM models due to its strength to reflect the nonlinearity of
      crash predictors and interaction impacts among variables under different ranges.
      Therefore, it can be recommended that the CMFs are estimated using MARS when
      there are nonlinear relationships between crash rate and roadway characteristics,
      and interaction impacts among multiple treatments. 

PMID- 26291922
TI  - Staging the Axilla in Early Breast Cancer: Will Imaging Replace Surgery?

PMID- 26291923
TI  - Putative Lineage of Novel African Usutu Virus, Central Europe.
AB  - We characterized the complete genome of a putative novel Usutu virus (USUV)
      strain (Usutu-BONN) detected in a dead blackbird from Germany. Genomic analysis
      revealed several unique amino acid substitutions among the polyprotein gene.
      Phylogenetic analyses demonstrated that Usutu-BONN constitutes a putative novel
      African USUV lineage, which was probably recently introduced to central Europe. 

PMID- 26291924
TI  - Training in Infectious Disease Epidemiology through the Emerging Infections
      Program Sites.
AB  - One objective of the Emerging Infections Program (EIP) of the US Centers for
      Disease Control and Prevention is to provide training opportunities in infectious
      disease epidemiology. To determine the extent of training performed since the
      program's inception in 1995, we reviewed training efforts at the 10 EIP sites. By
      2015, all sites hosted trainees (most were graduate public health students and
      physicians) who worked on a variety of infectious disease surveillance and
      epidemiologic projects. Trainee projects at all sites were used for graduate
      student theses or practicums. Numerous projects resulted in conference
      presentations and publications in peer-reviewed journals. Local public health and
      health care partners have also benefitted from EIP presentations and training.
      Consideration should be given to standardizing and documenting EIP training and
      to sharing useful training initiatives with other state and local health
      departments and academic institutions. 

PMID- 26291921
TI  - Cancer stem cells and the tumor microenvironment: interplay in tumor
      heterogeneity.
AB  - Tumor cells able to recapitulate tumor heterogeneity have been tracked, isolated
      and characterized in different tumor types, and are commonly named Cancer Stem
      Cells or Cancer Initiating Cells (CSC/CIC). CSC/CIC are disseminated in the tumor
      mass and are resistant to anti-cancer therapies and adverse conditions. They are
      able to divide into another stem cell and a "proliferating" cancer cell. They
      appear to be responsible for disease recurrence and metastatic dissemination even
      after apparent eradication of the primary tumor. The modulation of CSC/CIC
      activities by the tumor microenvironment (TUMIC) is still poorly known. CSC/CIC
      may mutually interact with the TUMIC in a special and unique manner depending on
      the TUMIC cells or proteins encountered. The TUMIC consists of extracellular
      matrix components as well as cellular players among which endothelial, stromal
      and immune cells, providing and responding to signals to/from the CSC/CIC. This
      interplay can contribute to the mechanisms through which CSC/CIC may reside in a
      dormant state in a tissue for years, later giving rise to tumor recurrence or
      metastasis in patients. Different TUMIC components, including the connective
      tissue, can differentially activate CIC/CSC in different areas of a tumor and
      contribute to the generation of cancer heterogeneity. Here, we review possible
      networking activities between the different components of the tumor
      microenvironment and CSC/CIC, with a focus on its role in tumor heterogeneity and
      progression. We also summarize novel therapeutic options that could target both
      CSC/CIC and the microenvironment to elude resistance mechanisms activated by
      CSC/CIC, responsible for disease recurrence and metastases. 

PMID- 26291925
TI  - Intraductal Carcinoma of the Prostate.

PMID- 26291927
TI  - Editorial Comment.

PMID- 26291928
TI  - Facile Fabrication of N-Doped Graphene as Efficient Electrocatalyst for Oxygen
      Reduction Reaction.
AB  - A facile bottom-up method is reported here for the fabrication of N-doped
      graphene for oxygen reduction. It consists of a two-step calcination strategy and
      uses alpha-hydroxy acids (AHAs) as carbon source and melamine as nitrogen source.
      Three different AHAs, malic acid, tartaric acid, and citric acid, were chosen as
      the carbon sources. The prepared N-doped graphenes have a typical thin layered
      structure with a large specific surface area. It was found that the N content in
      the obtained N-doped graphenes varies from 4.12 to 8.11 at. % depending on the
      AHAs used. All of the samples showed high performance in oxygen reduction
      reaction (ORR). The N-doped graphene prepared from citric acid demonstrated the
      highest electrocatalytic activity, which is comparable to the commercial Pt/C and
      exhibited good durability, attributing to the high pyridinic N content in the
      composite. 

PMID- 26291929
TI  - WHAMM links actin assembly via the Arp2/3 complex to autophagy.
AB  - Macroautophagy (hereafter autophagy) is the process by which cytosolic material
      destined for degradation is enclosed inside a double-membrane cisterna known as
      the autophagosome and processed for secretion and/or recycling. This process
      requires a large collection of proteins that converge on certain sites of the ER
      membrane to generate the autophagosome membrane. Recently, it was shown that
      actin accumulates around autophagosome precursors and could play a role in this
      process, but the mechanism and role of actin polymerization in autophagy were
      unknown. Here, we discuss our recent finding that the nucleation-promoting factor
      (NPF) WHAMM recruits and activates the Arp2/3 complex for actin assembly at sites
      of autophagosome formation on the ER. Using high-resolution, live-cell imaging,
      we showed that WHAMM forms dynamic puncta on the ER that comigrate with several
      autophagy markers, and propels the spiral movement of these puncta by an Arp2/3
      complex-dependent actin comet tail mechanism. In starved cells, WHAMM accumulates
      at the interface between neighboring autophagosomes, whose number and size
      increases with WHAMM expression. Conversely, knocking down WHAMM, inhibiting the
      Arp2/3 complex or interfering with actin polymerization reduces the size and
      number of autophagosomes. These findings establish a link between Arp2/3 complex
      mediated actin assembly and autophagy. 

PMID- 26291935
TI  - State-specific electron transfer: Shake it off.

PMID- 26291936
TI  - Perovskite solar cells: Crystal crosslinking.

PMID- 26291937
TI  - C-H activation: Following directions.

PMID- 26291938
TI  - Metalloproteins: The long and the short of it.

PMID- 26291939
TI  - On the mechanism of vibrational control of light-induced charge transfer in donor
      bridge-acceptor assemblies.
AB  - Nuclear-electronic (vibronic) coupling is increasingly recognized as a mechanism
      of major importance in controlling the light-induced function of molecular
      systems. It was recently shown that infrared light excitation of intramolecular
      vibrations can radically change the efficiency of electron transfer, a
      fundamental chemical process. We now extend and generalize the understanding of
      this phenomenon by probing and perturbing vibronic coupling in several molecules
      in solution. In the experiments an ultrafast electronic-vibrational pulse
      sequence is applied to a range of donor-bridge-acceptor Pt(II) trans-acetylide
      assemblies, for which infrared excitation of selected bridge vibrations during
      ultraviolet-initiated charge separation alters the yields of light-induced
      product states. The experiments, augmented by quantum chemical calculations,
      reveal a complex combination of vibronic mechanisms responsible for the observed
      changes in electron transfer rates and pathways. The study raises new fundamental
      questions about the function of vibrational processes immediately following
      charge transfer photoexcitation, and highlights the molecular features necessary
      for external vibronic control of excited-state processes. 

PMID- 26291940
TI  - Significantly shorter Fe-S bond in cytochrome P450-I is consistent with greater
      reactivity relative to chloroperoxidase.
AB  - Cytochrome P450 (P450) and chloroperoxidase (CPO) are thiolate-ligated haem
      proteins that catalyse the activation of carbon hydrogen bonds. The principal
      intermediate in these reactions is a ferryl radical species called compound I.
      P450 compound I (P450-I) is significantly more reactive than CPO-I, which only
      cleaves activated C-H bonds. To provide insight into the differing reactivities
      of these intermediates, we examined CPO-I and P450-I using variable-temperature
      Mossbauer and X-ray absorption spectroscopies. These measurements indicate that
      the Fe-S bond is significantly shorter in P450-I than in CPO-I. This difference
      in Fe-S bond lengths can be understood in terms of variations in the hydrogen
      bonding patterns within the 'cys-pocket' (a portion of the proximal helix that
      encircles the thiolate ligand). Weaker hydrogen bonding in P450-I results in a
      shorter Fe-S bond, which enables greater electron donation from the axial
      thiolate ligand. This observation may in part explain P450's greater propensity
      for C-H bond activation. 

PMID- 26291941
TI  - Improved performance and stability of perovskite solar cells by crystal
      crosslinking with alkylphosphonic acid omega-ammonium chlorides.
AB  - In the past few years, organic-inorganic halide perovskites have rapidly emerged
      as promising materials for photovoltaic applications, but simultaneously
      achieving high performance and long-term stability has proved challenging. Here,
      we show a one-step solution-processing strategy using phosphonic acid ammonium
      additives that results in efficient perovskite solar cells with enhanced
      stability. We modify the surface of methylammonium lead triiodide (CH3NH3PbI3)
      perovskite by spin-coating its precursor solution in the presence of
      butylphosphonic acid 4-ammonium chloride. Morphological, structural and elemental
      analyses show that the phosphonic acid ammonium additive acts as a crosslink
      between neighbouring grains in the perovskite structure, through strong hydrogen
      bonding of the -PO(OH)2 and -NH3(+) terminal groups to the perovskite surface.
      The additives facilitate the incorporation of the perovskite within a mesoporous
      TiO2 scaffold, as well as the growth of a uniform perovskite layer at the
      surface, enhancing the material's photovoltaic performance from 8.8 to 16.7% as
      well as its resistance to moisture. 

PMID- 26291943
TI  - Catalytic living ring-opening metathesis polymerization.
AB  - In living ring-opening metathesis polymerization (ROMP), a transition-metal
      carbene complex polymerizes ring-strained olefins with very good control of the
      molecular weight of the resulting polymers. Because one molecule of the initiator
      is required for each polymer chain, however, this type of polymerization is
      expensive for widespread use. We have now designed a chain-transfer agent (CTA)
      capable of reducing the required amount of metal complex while still maintaining
      full control over the living polymerization process. This new method introduces a
      degenerative transfer process to ROMP. We demonstrate that substituted
      cyclohexene rings are good CTAs, and thereby preserve the 'living' character of
      the polymerization using catalytic quantities of the metal complex. The resulting
      polymers show characteristics of a living polymerization, namely narrow molecular
      weight distribution, controlled molecular weights and block copolymer formation.
      This new technique provides access to well-defined polymers for industrial,
      biomedical and academic use at a fraction of the current costs and significantly
      reduced levels of residual ruthenium catalyst. 

PMID- 26291942
TI  - A meta-selective C-H borylation directed by a secondary interaction between
      ligand and substrate.
AB  - Regioselective C-H bond transformations are potentially the most efficient method
      for the synthesis of organic molecules. However, the presence of many C-H bonds
      in organic molecules and the high activation barrier for these reactions make
      these transformations difficult. Directing groups in the reaction substrate are
      often used to control regioselectivity, which has been especially successful for
      the ortho-selective functionalization of aromatic substrates. Here, we describe
      an iridium-catalysed meta-selective C-H borylation of aromatic compounds using a
      newly designed catalytic system. The bipyridine-derived ligand that binds iridium
      contains a pendant urea moiety. A secondary interaction between this urea and a
      hydrogen-bond acceptor in the substrate places the iridium in close proximity to
      the meta-C-H bond and thus controls the regioselectivity. (1)H NMR studies and
      control experiments support the participation of hydrogen bonds in inducing
      regioselectivity. Reversible direction of the catalyst through hydrogen bonds is
      a versatile concept for regioselective C-H transformations. 

PMID- 26291944
TI  - Asymmetric assembly of aldose carbohydrates from formaldehyde and glycolaldehyde
      by tandem biocatalytic aldol reactions.
AB  - The preparation of multifunctional chiral molecules can be greatly simplified by
      adopting a route via the sequential catalytic assembly of achiral building
      blocks. The catalytic aldol assembly of prebiotic compounds into stereodefined
      pentoses and hexoses is an as yet unmet challenge. Such a process would be of
      remarkable synthetic utility and highly significant with regard to the origin of
      life. Pursuing an expedient enzymatic approach, here we use engineered D-fructose
      6-phosphate aldolase from Escherichia coli to prepare a series of three- to six
      carbon aldoses by sequential one-pot additions of glycolaldehyde. Notably, the
      pertinent selection of the aldolase variant provides control of the sugar size.
      The stereochemical outcome of the addition was also altered to allow the
      synthesis of L-glucose and related derivatives. Such engineered biocatalysts may
      offer new routes for the straightforward synthesis of natural molecules and their
      analogues that circumvent the intricate enzymatic pathways forged by evolution. 

PMID- 26291945
TI  - Ultrahigh-throughput exfoliation of graphite into pristine 'single-layer'
      graphene using microwaves and molecularly engineered ionic liquids.
AB  - Graphene has shown much promise as an organic electronic material but, despite
      recent achievements in the production of few-layer graphene, the quantitative
      exfoliation of graphite into pristine single-layer graphene has remained one of
      the main challenges in developing practical devices. Recently, reduced graphene
      oxide has been recognized as a non-feasible alternative to graphene owing to
      variable defect types and levels, and attention is turning towards reliable
      methods for the high-throughput exfoliation of graphite. Here we report that
      microwave irradiation of graphite suspended in molecularly engineered oligomeric
      ionic liquids allows for ultrahigh-efficiency exfoliation (93% yield) with a high
      selectivity (95%) towards 'single-layer' graphene (that is, with thicknesses <1
      nm) in a short processing time (30 minutes). The isolated graphene sheets show
      negligible structural deterioration. They are also readily redispersible in
      oligomeric ionic liquids up to ~100 mg ml(-1), and form physical gels in which an
      anisotropic orientation of graphene sheets, once induced by a magnetic field, is
      maintained. 

PMID- 26291946
TI  - Use of a biosynthetic intermediate to explore the chemical diversity of pseudo
      natural fungal polyketides.
AB  - The structural complexity and diversity of natural products make them attractive
      sources for potential drug discovery, with their characteristics being derived
      from the multi-step combination of enzymatic and non-enzymatic conversions of
      intermediates in each biosynthetic pathway. Intermediates that exhibit
      multipotent behaviour have great potential for use as starting points in
      diversity-oriented synthesis. Inspired by the biosynthetic pathways that form
      complex metabolites from simple intermediates, we developed a semi-synthetic
      process that combines heterologous biosynthesis and artificial diversification.
      The heterologous biosynthesis of fungal polyketide intermediates led to the
      isolation of novel oligomers and provided evidence for ortho-quinonemethide
      equivalency in their isochromene form. The intrinsic reactivity of the
      isochromene polyketide enabled us to access various new chemical entities by
      modifying and remodelling the polyketide core and through coupling with indole
      molecules. We thus succeeded in generating exceptionally diverse pseudo-natural
      polyketides through this process and demonstrated an advanced method of using
      biosynthetic intermediates. 

PMID- 26291947
TI  - Synthesis of marmycin A and investigation into its cellular activity.
AB  - Anthracyclines such as doxorubicin are used extensively in the treatment of
      cancers. Anthraquinone-related angucyclines also exhibit antiproliferative
      properties and have been proposed to operate via similar mechanisms, including
      direct genome targeting. Here, we report the chemical synthesis of marmycin A and
      the study of its cellular activity. The aromatic core was constructed by means of
      a one-pot multistep reaction comprising a regioselective Diels-Alder
      cycloaddition, and the complex sugar backbone was introduced through a copper
      catalysed Ullmann cross-coupling, followed by a challenging Friedel-Crafts
      cyclization. Remarkably, fluorescence microscopy revealed that marmycin A does
      not target the nucleus but instead accumulates in lysosomes, thereby promoting
      cell death independently of genome targeting. Furthermore, a synthetic dimer of
      marmycin A and the lysosome-targeting agent artesunate exhibited a synergistic
      activity against the invasive MDA-MB-231 cancer cell line. These findings shed
      light on the elusive pathways through which anthraquinone derivatives act in
      cells, pointing towards unanticipated biological and therapeutic applications. 

PMID- 26291948
TI  - Organocatalytic removal of formaldehyde adducts from RNA and DNA bases.
AB  - Formaldehyde is universally used to fix tissue specimens, where it forms
      hemiaminal and aminal adducts with biomolecules, hindering the ability to
      retrieve molecular information. Common methods for removing these adducts involve
      extended heating, which can cause extensive degradation of nucleic acids,
      particularly RNA. Here, we show that water-soluble bifunctional catalysts
      (anthranilates and phosphanilates) speed the reversal of formaldehyde adducts of
      mononucleotides over standard buffers. Studies with formaldehyde-treated RNA
      oligonucleotides show that the catalysts enhance adduct removal, restoring
      unmodified RNA at 37  degrees C even when extensively modified, while avoiding
      the high temperatures that promote RNA degradation. Experiments with formalin
      fixed, paraffin-embedded cell samples show that the catalysis is compatible with
      common RNA extraction protocols, with detectable RNA yields increased by 1.5-2.4
      fold using a catalyst under optimized conditions and by 7-25-fold compared with a
      commercial kit. Such catalytic strategies show promise for general use in
      reversing formaldehyde adducts in clinical specimens. 

PMID- 26291950
TI  - Erratum: Chemoselective conversion of biologically sourced polyols into chiral
      synthons.

PMID- 26291949
TI  - Corrigendum: Cloud-based simulations on Google Exacycle reveal ligand modulation
      of GPCR activation pathways.

PMID- 26291951
TI  - Seaborgium's complex studies.

PMID- 26291952
TI  - Separating the Laparoscopic Camera Cord From the Monopolar "Bovie" Cord Reduces
      Unintended Thermal Injury From Antenna Coupling: A Randomized Controlled Trial.
AB  - OBJECTIVE(S): The monopolar "Bovie" is used in virtually every laparoscopic
      operation. The active electrode and its cord emit radiofrequency energy that
      couples (or transfers) to nearby conductive material without direct contact. This
      phenomenon is increased when the active electrode cord is oriented parallel to
      another wire/cord. The parallel orientation of the "Bovie" and laparoscopic
      camera cords cause transfer of energy to the camera cord resulting in cutaneous
      burns at the camera trocar incision. We hypothesized that separating the active
      electrode/camera cords would reduce thermal injury occurring at the camera trocar
      incision in comparison to parallel oriented active electrode/camera cords.
      METHODS: In this prospective, blinded, randomized controlled trial, patients
      undergoing standardized laparoscopic cholecystectomy were randomized to separated
      active electrode/camera cords or parallel oriented active electrode/camera cords.
      The primary outcome variable was thermal injury determined by histology from skin
      biopsied at the camera trocar incision. RESULTS: Eighty-four patients
      participated. Baseline demographics were similar in the groups for age, sex,
      preoperative diagnosis, operative time, and blood loss. Thermal injury at the
      camera trocar incision was lower in the separated versus parallel group (31% vs
      57%; P = 0.027). CONCLUSIONS: Separation of the laparoscopic camera cord from the
      active electrode cord decreases thermal injury from antenna coupling at the
      camera trocar incision in comparison to the parallel orientation of these cords.
      Therefore, parallel orientation of these cords (an arrangement promoted by
      integrated operating rooms) should be abandoned. The findings of this study
      should influence the operating room setup for all laparoscopic cases.

PMID- 26291953
TI  - Randomized Controlled Trial of Laparoscopic and Open Nissen Fundoplication in
      Children.
AB  - OBJECTIVE: The aim was to compare recurrence of gastroesophageal reflux disease
      (GERD) in children randomized to laparoscopic (LF) or open Nissen fundoplication
      (OF). BACKGROUND: LF is considered superior to OF by most pediatric surgeons even
      though this has not been shown in any randomized controlled trial in children.
      METHODS: Patients referred for fundoplication between 2003 and 2009 were eligible
      for inclusion in this 2-center, unstratified, randomized, parallel-group study
      conducted in Norway. The main outcome measure was recurrence of GERD, which was
      defined as GERD combined with a reflux index greater than 4 on pH monitoring
      and/or gastroesophageal reflux and/or herniated wrap on upper gastrointestinal
      (UGI) contrast study. Only experienced laparoscopic surgeons performed the LF.
      Postoperative follow-up included 24-hour pH monitoring, UGI contrast study, and a
      clinical examination at 6 months and phone interviews after 1, 2, and 4 years.
      RESULTS: Eighty-seven children were included and randomized to either LF (n = 44)
      or OF (n = 43). Median age was 4.7 years (0.2-15.4) in the LF group and 3.7 years
      (0.2-14.2) in the OF group. Twenty-three patients in both groups were
      neurologically impaired. Median follow-up time was 4.0 years (0.3-8.9).
      Significantly more patients undergoing LF (37%) experienced recurrence of GERD
      compared to those undergoing OF (7%); risk ratio for recurrence in the LF group
      was 5.2 (95% confidence interval: 1.6-16.6) (P = 0.001). CONCLUSIONS: Children
      operated with LF have a higher recurrence rate of GERD than those operated with
      OF.

PMID- 26291954
TI  - The Impact of Operating Room Distractions on Stress, Workload, and Teamwork.
AB  - OBJECTIVE: To investigate whether distractions in the operating room (OR) are
      associated with higher mental workload and stress, and poorer teamwork among OR
      personnel. BACKGROUND: Engaging in multiple tasks can affect performance. There
      is little research on the effect of distractions on surgical team members'
      behavior and cognitive processes. METHODS: Ninety general surgery cases were
      observed in real time. Cases were assessed by a surgeon and a behavioral
      scientist using 4 validated tools: OR Distractions Assessment Form, the
      Observational Teamwork Assessment for Surgery tool, NASA-Task Load Index, and
      short form of the State Trait Anxiety Inventory. Analysis of variance was
      performed to evaluate significant differences between teamwork, workload, and
      stress level among team members. Correlations (Pearson r) were computed to
      evaluate associations between variables. RESULTS: The most prevalent distractions
      were those initiated by external staff, followed by case-irrelevant
      conversations. Case-irrelevant conversations were associated with poorer team
      performance. Irrelevant conversations initiated by surgeons were associated with
      lower teamwork in surgeons (across team skills: r = -0.44 to -0.58, P < 0.05 to
      0.01) and anesthesiologists (r = -0.38 and r = -0.40, for coordination and
      leadership; P < 0.05). Equipment-related distractions correlated with higher
      stress (r = 0.48, P < 0.05) and lower teamwork (across team skills: r = -0.42 to 
      0.50, P < 0.05) in nurses. Acoustic distractions correlated with higher stress in
      surgeons (r = 0.32, P < 0.05) and higher workload in anesthesiologists (r = 0.30,
      P < 0.05). CONCLUSIONS: Although some distractions may be inevitable in the OR,
      they can also be detrimental to the team. A deeper understanding of the effect of
      distractions on teams and their outcomes can lead to targeted quality
      improvement.

PMID- 26291955
TI  - Better Survival But Changing Causes of Death in Patients With Multiple Endocrine
      Neoplasia Type 1.

PMID- 26291956
TI  - Complex Ancestries of Isoprenoid Synthesis in Dinoflagellates.
AB  - Isoprenoid metabolism occupies a central position in the anabolic metabolism of
      all living cells. In plastid-bearing organisms, two pathways may be present for
      de novo isoprenoid synthesis, the cytosolic mevalonate pathway (MVA) and nuclear
      encoded, plastid-targeted nonmevalonate pathway (DOXP). Using transcriptomic data
      we find that dinoflagellates apparently make exclusive use of the DOXP pathway.
      Using phylogenetic analyses of all DOXP genes we inferred the evolutionary
      origins of DOXP genes in dinoflagellates. Plastid replacements led to a DOXP
      pathway of multiple evolutionary origins. Dinoflagellates commonly referred to as
      dinotoms due to their relatively recent acquisition of a diatom plastid, express
      two completely redundant DOXP pathways. Dinoflagellates with a tertiary plastid
      of haptophyte origin, by contrast, express a hybrid pathway of dual evolutionary
      origin. Here, changes in the targeting motif of signal/transit peptide likely
      allow for targeting the new plastid by the proteins of core isoprenoid metabolism
      proteins. Parasitic dinoflagellates of the Amoebophyra species complex appear to
      have lost the DOXP pathway, suggesting that they may rely on their host for
      sterol synthesis. 

PMID- 26291958
TI  - Consistent rationalization of type-2 topoisomerases' unknotting, decatenating,
      supercoil-relaxing actions and their scaling relation.
AB  - How type-2 topoisomerases discern global topology from local properties of DNA is
      not known precisely but the hypothesis that the enzymes selectively pass double
      helix strands at hook-like juxtapositions is promising. Building upon an
      investigation of unknotting and decatenating using an improved wormlike DNA
      model, here we focus primarily on the enzymes' action in narrowing the
      distribution of linking number (Lk) in supercoiled DNA. Consistent with
      experiments, with selective passage at a hooked juxtaposition, the simulated
      narrowing factor RLk diminishes with decreasing DNA circle size but approaches an
      asymptotic RLk ~ 1.7-1.8 for circle size ?3.5 kb. For the larger DNA circles, we
      found that (RLk - 1) ~ 0.42log10RK ~ 0.68log10RL and thus RK ~ (RL)(1.6) holds
      for the computed RLk and knot and catenane reduction factors RK and RL attained
      by selective passage at different juxtaposition geometries. Remarkably, this
      general scaling relation is essentially identical to that observed experimentally
      for several type-2 topoisomerases from a variety of organisms, indicating that
      the different disentangling powers of the topoisomerases likely arise from
      variations in the hooked geometries they select. Taken together, our results
      suggest strongly that type-2 topoisomerases recognize not only the curvature of
      the G-segment but also that of the T-segment. 

PMID- 26291957
TI  - 7-Methoxy-(9H-beta-Carbolin-1-il)-(E)-1-Propenoic Acid, a beta-Carboline Alkaloid
      From Eurycoma longifolia, Exhibits Anti-Inflammatory Effects by Activating the
      Nrf2/Heme Oxygenase-1 Pathway.
AB  - Eurycoma longifolia is an herbal medicinal plant popularly used in Southeast
      Asian countries. In the present study, we show that 7-methoxy-(9H-beta-carbolin-1
      il)-(E)-1-propenoic acid (7-MCPA), a beta-carboline alkaloid isolated from E.
      longifolia, exerted anti-inflammatory effects by activating the nuclear factor-E2
      related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. 7-MCPA inhibited
      lipopolysaccharide (LPS)-induced production of nitric oxide (NO), prostaglandin
      E2 (PGE2 ), and interleukin-6 (IL-6) in RAW264.7 cells and rescued C57BL/6 mice
      from LPS-induced lethality in vivo. LPS-induced expression of inducible nitric
      oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and IL-6 was also significantly
      suppressed by treatment of 7-MCPA in RAW264.7 cells. 7-MCPA induced nuclear
      translocation of Nrf2 and increased transcription of its target genes, such as HO
      1. Treating RAW264.7 cells with 7-MCPA increased the intracellular level of
      reactive oxygen species (ROS) and the phosphorylation level of p38 mitogen
      activated protein kinase (MAPK); however, co-treatment with the antioxidant N
      acetyl-cysteine (NAC) blocked 7-MCPA-induced p38 MAPK phosphorylation. Moreover,
      NAC or SB203580 (p38 MAPK inhibitor) blocked 7-MCPA-induced nuclear translocation
      of Nrf2, suggesting that 7-MCPA activated Nrf2 via a ROS-dependent p38 pathway. 7
      MCPA induced HO-1 protein and mRNA expression and knockdown of Nrf2 with siRNA or
      SB203580 blocked 7-MCPA-mediated induction of HO-1 expression. Inhibiting Nrf2 or
      HO-1 abrogated the anti-inflammatory effects of 7-MCPA in LPS-stimulated RAW264.7
      cells. We also demonstrated that 7-MCPA suppressed LPS-induced nuclear factor
      kappaB (NF-kappaB) activation. These results provide the first evidence that 7
      MCPA exerts its anti-inflammatory effect by modulating the Nrf2 and NF-kappaB
      pathways and may be a potential Nrf2 activator to prevent or treat inflammatory
      diseases.

PMID- 26291959
TI  - Hematopoietic Stem Cell Transplantation for CD40 Ligand Deficiency: Single
      Institution Experience.
AB  - BACKGROUND: X-linked hyper-IgM syndrome (X-HIGM) due to mutations in the gene
      encoding CD40 ligand results in failure of Ig class switching and an increased
      propensity for recurrent sinopulmonary and other infections, and thus decreased
      life expectancy. Allogeneic hematopoietic stem cell transplantation (HSCT) is
      curative, but long-term follow-up data are limited. PROCEDURES: We conducted a
      retrospective analysis of seven patients who have undergone allogeneic HSCT for
      HIGM syndrome at Duke University Medical Center. RESULTS: Median age at
      transplant was 5.2 years (range 0.7-19.3). None of the patients had active
      hepatic or pulmonary disease immediately prior to transplant, but all had a
      history of serious infections. Five patients received myeloablative conditioning,
      and two patients received reduced intensity conditioning. Graft sources included
      bone marrow, peripheral blood, and unrelated umbilical cord blood. Post
      transplantation complications included veno-occlusive disease, hemorrhagic
      cystitis, adenoviremia, and cryptosporidium recurrence in one patient each. Two
      patients developed acute GVHD grades II-IV that resolved promptly with treatment
      and none developed extensive chronic GVHD. All patients are intravenous IgG
      independent and 6/7 have normal antibody titers. Immunoglobulin (Ig) A levels
      normalized in all but one patient and T and B cell numbers and function are
      otherwise normal in all. All patients are alive at a median follow-up of 9.7
      (range 9.7-16.1) years post-transplantation with predominantly donor chimerism
      and no recurrent infections. CONCLUSIONS: Allogeneic HSCT results in excellent
      survival and sustained immune reconstitution in patients with CD40 ligand
      deficiency using both myeloablative and reduced intensity conditioning approaches
      and various graft sources, including bone marrow, peripheral blood, and umbilical
      cord blood.

PMID- 26291960
TI  - An automatic method for atom identification in scanning tunnelling microscopy
      images of Fe-chalcogenide superconductors.
AB  - We describe a computational approach for the automatic recognition and
      classification of atomic species in scanning tunnelling microscopy images. The
      approach is based on a pipeline of image processing methods in which the
      classification step is performed by means of a Fuzzy Clustering algorithm. As a
      representative example, we use the computational tool to characterize the
      nanoscale phase separation in thin films of the Fe-chalcogenide superconductor
      FeSex Te1-x , starting from synthetic data sets and experimental topographies. We
      quantify the stoichiometry fluctuations on length scales from tens to a few
      nanometres. 

PMID- 26291961
TI  - Intelligent DNA machine for the ultrasensitive colorimetric detection of nucleic
      acids.
AB  - As DNA is employed to serve as a smart building block, an increasing interest has
      been devoted to the development of different DNA-based machines for the specific
      purpose, for example, the exploration of inter- or intramolecular interaction. In
      the current contribution, we developed an intelligent DNA machine and its
      operation can be designed to execute the ultrasensitive colorimetric detection of
      target nucleic acids. The DNA machine consists of a hairpin probe (HP) and an
      assistant template (AT). Using p53 gene as the target model to trigger the
      molecular machine operation, cyclic nucleic acid strand displacement
      polymerization (CNDP) was specifically induced, leading to the DNAzyme mediated
      catalytic reaction for signal readout. Specifically, with the help of polymerase
      and nickase, one target molecule was able to drive DNA nano-mechanical devices
      one-by-one through the hybridization/polymerization displacement cycles, and
      every initiated machine continued to operate, causing the dramatic accumulation
      of G-quadruplex-contained products. The G-quadruplex structure after binding to
      hemin could act as a horseradish peroxidase (HRP)-mimicking DNAzyme and catalyzed
      the oxidation of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) by
      H2O2. As a result, an enhanced color change could be detected because of the
      generation of oxidation product ABTS*(+). In this way, the DNA machine has no any
      signal loss and enables the quantitative measurement of p53 DNA with a detection
      limit of 10fM, indicating great promise for unique application in biomedical
      research and early clinical diagnosis. 

PMID- 26291962
TI  - Celecoxib adjunctive therapy for acute bipolar mania: a randomized, double-blind,
      placebo-controlled trial.
AB  - OBJECTIVES: Recent research has focused on the inflammatory cascade as a key
      culprit in the etiology of bipolar disorder. We hypothesized that celecoxib, via
      its anti-inflammatory properties, may have a therapeutic role in mood disorder.
      METHODS: Forty-six inpatients with the diagnosis of acute bipolar mania without
      psychotic features participated in a parallel, randomized, double-blind, placebo
      controlled trial, and underwent six weeks of treatment with either celecoxib (400
      mg daily) or placebo as an adjunctive treatment to sodium valproate. Patients
      were evaluated using the Young Mania Rating Scale (YMRS) and Hamilton Depression
      Rating Scale (HDRS). The primary outcome measure with respect to efficacy was the
      mean decrease in YMRS score from baseline to the study endpoint, which was
      compared between the two groups. RESULTS: A significant difference was observed
      in the change in YMRS scores on Day 42 compared to baseline in the two groups (p
      < 0.001). The changes at the endpoint compared to baseline were -29.78 +/- 21.78
      (mean +/- standard deviation) and -21.78 +/- 7.16 for the celecoxib and placebo
      groups, respectively. A significantly higher remission rate was observed in the
      celecoxib group (87.0%) than the placebo group (43.5%) at Week 6 (p = 0.005).
      General linear model repeated measures demonstrated a significant effect for the
      time * treatment interaction on the YMRS scores [F(2.27,99.98) = 6.67, p =
      0.001]. CONCLUSIONS: Celecoxib is an effective adjuvant therapy in the treatment
      of manic episodes (without psychotic features) of bipolar mood disorder. The mood
      stabilizing role of the drug might be mediated via its action on the inflammatory
      cascade.

PMID- 26291963
TI  - The role of azithromycin in healthcare-associated pneumonia treatment.
AB  - WHAT IS KNOWN AND OBJECTIVE: Healthcare-associated pneumonia (HCAP) is an
      important presentation among hospitalized patients. Standardized definitions of
      this entity are almost a decade old, and practice patterns have shifted from
      published guidelines to include empiric coverage with a macrolide, such as
      azithromycin. Azithromycin is oftentimes included in the empiric treatment
      regimen for HCAP because of the importance of appropriate empiric antimicrobial
      coverage, the perceived concern regarding atypical organisms, potential anti
      inflammatory effects of the medication, and positive clinical data among patients
      with Streptococcal bacteremia. METHODS: In this review, we systematically
      investigate data for each of these topics along with clinical data examining the
      role of azithromycin in HCAP. RESULTS AND DISCUSSION: Our findings indicate that
      atypical organisms are rare in HCAP, that the anti-inflammatory actions of
      azithromycin - although promising - have not produced consistently positive
      effects in many chronic or acute conditions, and that the data available for
      azithromycin use in bacteremia are of low quality. A single-centre cohort
      indicated that the clinical benefits of azithromycin did not extend to HCAP
      compared to community-acquired pneumonia. WHAT IS NEW AND CONCLUSION:
      Additionally, there are newer data emphasizing the potential cardiotoxicity of
      azithromycin, particularly among patients at high risk. All of these data
      indicate that azithromycin should not be part of the standard empiric treatment
      for HCAP.

PMID- 26291964
TI  - Three-dimensional corrective osteotomies of mal-united clavicles--is the
      contralateral anatomy a reliable template for reconstruction?
AB  - In computer-assisted preoperative planning of corrective osteotomies, the
      unaffected contralateral bone often serves as three-dimensional template for the
      reconstruction of mal-united bones. Before applying this approach to new anatomy
      such as the clavicle bone, it is important to study asymmetry between the sides.
      The purpose of this study was to investigate bilateral symmetry of the clavicle
      in healthy cadavers using three-dimensional measurement techniques. Bilateral
      symmetry of 102 clavicles (51 cadavers, mean age: 52.19 years, 37 male) was
      measured based on three-dimensional models reconstructed from computed
      tomography. Besides length, volume, and surface, the side-differences were
      evaluated by considering the mirrored left clavicle as the reconstruction
      template and the right clavicle as the one that will be realigned by osteotomy.
      The relative transformation between the aligned segments was measured to express
      the difference with to three-dimensional translation and rotation. The same
      procedure was repeated using mean-sized clavicles, one for each gender, as the
      template. The contralateral side was a significant more accurate reconstruction
      template compared to a mean-sized clavicle (P < 0.001). Nevertheless, an average
      side-differences with respect to rotation and translation of 8.79 degrees  +/-
      5.2 degrees  and 3.5 mm +/- 2.7 mm, respectively. The left clavicles were
      significant (P = 0.001) longer with 154 mm compared to the right ones (151 mm).
      Three-dimensional differences between the left and right clavicles exist, but can
      be considered as small. Therefore, the contralateral side appears to be a
      reliable reconstruction template, in particular compared to a mean-sized
      clavicle.

PMID- 26291966
TI  - Congenital Recessive Methemoglobinemia Revealed in Adulthood: Description of a
      New Mutation in Cytochrome b5 Reductase Gene.
AB  - Methemoglobinemia can be acquired (oxidizing drugs or chemicals products) or
      inherited either by mutations affecting globin chains [M hemoglobins (M Hbs)] or
      by defects in the enzymatic system involved in the reduction of spontaneous Hb
      oxidation: nicotinamide adenine dinucleotide (NADH)-cytochrome b5 reductase. It
      is encoded by the CYB5R3 gene: there are two phenotypes of autosomal recessive
      congenital methemoglobinemia, in type II CYB5R deficiency is generalized and
      affects all cells, leading to an early onset, whereas in type I, the enzyme
      deficiency is restricted to erythrocytes, usually discovered in infancy but not
      exclusively. We report a new case of methemoglobinemia discovered in a patient
      from Bahrain who exhibited an unknown dyspnea at the age of 37 years without
      trigger events or oxidizing products. We discovered a new mutation in the CYB5R3
      gene: exon 9, codon 266 (delGAG) (GLU) (CYB5R3: c.726_729delGAG) in the
      homozygous state. Appearance of methemoglobinemia in an adult usually suggests an
      acquired cause but our case illustrated that it could also reveal a type I
      mutation of cytochrome b5 reductase. 

PMID- 26291965
TI  - Rhoptry Proteins ROP5 and ROP18 Are Major Murine Virulence Factors in Genetically
      Divergent South American Strains of Toxoplasma gondii.
AB  - Toxoplasma gondii has evolved a number of strategies to evade immune responses in
      its many hosts. Previous genetic mapping of crosses between clonal type 1, 2, and
      3 strains of T. gondii, which are prevalent in Europe and North America,
      identified two rhoptry proteins, ROP5 and ROP18, that function together to block
      innate immune mechanisms activated by interferon gamma (IFNg) in murine hosts.
      However, the contribution of these and other virulence factors in more
      genetically divergent South American strains is unknown. Here we utilized a cross
      between the intermediately virulent North American type 2 ME49 strain and the
      highly virulent South American type 10 VAND strain to map the genetic basis for
      differences in virulence in the mouse. Quantitative trait locus (QTL) analysis of
      this new cross identified one peak that spanned the ROP5 locus on chromosome XII.
      CRISPR-Cas9 mediated deletion of all copies of ROP5 in the VAND strain rendered
      it avirulent and complementation confirmed that ROP5 is the major virulence
      factor accounting for differences between type 2 and type 10 strains. To extend
      these observations to other virulent South American strains representing distinct
      genetic populations, we knocked out ROP5 in type 8 TgCtBr5 and type 4 TgCtBr18
      strains, resulting in complete loss of virulence in both backgrounds. Consistent
      with this, polymorphisms that show strong signatures of positive selection in
      ROP5 were shown to correspond to regions known to interface with host immunity
      factors. Because ROP5 and ROP18 function together to resist innate immune
      mechanisms, and a significant interaction between them was identified in a two
      locus scan, we also assessed the role of ROP18 in the virulence of South American
      strains. Deletion of ROP18 in South American type 4, 8, and 10 strains resulted
      in complete attenuation in contrast to a partial loss of virulence seen for ROP18
      knockouts in previously described type 1 parasites. These data show that ROP5 and
      ROP18 are conserved virulence factors in genetically diverse strains from North
      and South America, suggesting they evolved to resist innate immune defenses in
      ancestral T. gondii strains, and they have subsequently diversified under
      positive selection. 

PMID- 26291967
TI  - Molecular Scanning of beta-Thalassemia in the Southern Region of Central Java,
      Indonesia; a Step Towards a Local Prevention Program.
AB  - Thalassemia is the most prevalent genetic blood disorder worldwide, and
      particularly prevalent in Indonesia. The purpose of this study was to determine
      the spectrum of beta-thalassemia (beta-thal) mutations found in the southern
      region of Central Java, Indonesia. The subjects of the study included 209 beta
      thal Javanese patients from Banyumas Residency, a southwest region of Central
      Java Province. DNA analysis was performed using polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP), amplification refractory
      mutation system (ARMS), and the direct sequencing method. The results showed that
      14 alleles were found in the following order: IVS-I-5 (G > C) (HBB: c.92 + 5G >
      C) 43.5%, codon 26 (Hb E; HBB: c.79G > A) 28.2%, IVS-I-1 (G > A) (HBB: c.92 + 1G
      > A) 5.0%, codon 15 (TGG > TAG) (HBB: c.47G > A) 3.8%, IVS-I-1 (G > T) (HBB: c.92
      + 1G > T) 3.1%, codon 35 (-C) (HBB: c.110delC) 2.4%. The rest, including codons
      41/42 (-TTCT) (HBB: c.126_129delCTTT), codons 8/9 (+G) (HBB: c.27_28insG), codon
      19 (AAC > AGC) (HBB: c.59A > G), codon 17 (AAG > TAG) (HBB: c.52A > T), IVS-I-2
      (T > C) (HBB: c.92 + 2T > C), codons 123/124/125 (-ACCCCACC) (HBB:
      c.370_378delACCCCACCA), codon 40 (-G) (HBB: c.123delG) and Cap +1 (A > C) (HBB:
      c.-50A > C), accounted for up to 1.0% each. The most prevalent alleles would be
      recommended to be used as part of beta-thal screening for the Javanese, one of
      the major ethnic groups in the country. 

PMID- 26291968
TI  - Hb G-Waimanalo [A1] [alpha64(E13)Asp->Asn; HBA1: c.193 G > A] with Decreased
      Oxygen Affinity.
AB  - A clinically asymptomatic 12-year-old girl showed microcytosis in routine
      examination. Cation exchange high performance liquid chromatography (HPLC),
      revealed two additional peaks eluting after Hb A and DNA sequencing uncovered a
      novel heterozygous mutation at codon 64 of the alpha1-globin gene. The hemoglobin
      (Hb) variant was annotated as Hb G-Waimanalo [A1]. Further analyses demonstrated
      a decreased oxygen affinity Hb compared to the normal Hb configuration. 

PMID- 26291969
TI  - Nomenclature Confusion in Deletion Mutations Involving Repetitive Nucleotides: A
      Lesson from HBB Gene Codon 35 (-C) vs. Codon 36 (-C).

PMID- 26291970
TI  - beta-Thalassemia Intermedia Caused by Compound Heterozygosity for Hb Lepore
      Hollandia and beta-Thalassemia is Rare in the Indian Population.
AB  - Compound heterozygosity for one of the Hb Lepore mutations and beta-thalassemia
      (beta-thal) is a rare cause of non transfusion-dependent thalassemia. We report a
      4-year-old boy who presented clinically as homozygous/compound heterozygous beta
      thal intermedia (beta-TI), an impression that was corroborated by the initial
      hemoglobin (Hb) high performance liquid chromatography (HPLC). However, the
      correct diagnosis of a rare compound heterozygous Hb Lepore-Hollandia/beta-thal
      was revealed after parental studies and molecular analyses including beta-globin
      gene sequencing. Our patient highlights the importance of a logical stepwise
      multi modality approach and the vital importance of parental screening and
      molecular studies in accurate characterization of complex hemoglobinopathies.
      Correct diagnosis is especially crucial if pre natal detection is anticipated for
      future pregnancies. Molecular analyses alone may not compensate for the
      unavailability of parental testing. This is because the molecular results may be
      misinterpreted, especially if limited tests are conducted. The infrequent prior
      reports of this combination from distant parts of the Indian subcontinent
      suggests that the origin of Hb Lepore-Hollandia from sporadic mutations occurs in
      isolated families. 

PMID- 26291971
TI  - A Novel Heme Pocket Hemoglobin Variant Associated with Normal Hematology: Hb Zara
      or alpha91(FG3)Leu->Ile (alpha2) (HBA2: c.274C > A).
AB  - We report a new hemoglobin (Hb) variant on the HBA2 gene, Hb Zara
      [alpha91(FG3)Leu->Ile (alpha2); HBA2: c.274C > A], which was found in a Caucasian
      man from Croatia. It was observed by routine cation exchange chromatography as an
      abnormal 21.8% fraction overlapping Hb A2, and associated with normal hematology.
      It was slightly unstable by the standard isopropanol precipitation test. DNA
      analysis revealed the CTT > ATT mutation at codon 91 on an alpha2 gene of a
      normal alpha-globin gene arrangement. This new variant represents the sixth
      described mutation at codon alpha91 and fourth on the alpha2 locus. As a result
      of the slight instability due to the significant role of the alpha91 residue in
      the alpha1beta2 contact, the level of the Hb Zara variant was lower than levels
      observed for several stable variants codified by the alpha2 locus. 

PMID- 26291972
TI  - First Description of a beta-Thalassemia Mutation, -86 (C > G) (HBB: c.-136C > G),
      in a Chinese Family.
AB  - We present the first description of a Chinese family with a beta-thalassemia
      (beta-thal) mutation -86 (C > G) (HBB: c.-136C > G). This mutation changes the
      conserved promoter sequence within the proximal CACCC box of the beta-globin gene
      that leads to a phenotype of beta(+)-thal. The beta-globin haplotype analysis
      revealed that the -86 mutation in our case was linked with haplotype I [+ - - - -
      + +]. This haplotype was commonly found both in the beta-thal mutation and the
      beta(A) gene. Our results suggest that the -86 mutation possibly does not have a
      distinct origin. 

PMID- 26291974
TI  - Incorrect interpretation of AIMS trial analyses: comment on Mathes et al.'s
      'Response to letter ...' (HIV Medicine 2014, 15, 383-384).

PMID- 26291973
TI  - Evaluation of Left Ventricle Function by Regional Fractional Area Change (RFAC)
      in a Mouse Model of Myocardial Infarction Secondary to Valsartan Treatment.
AB  - AIM: Left ventricle (LV) regional fractional area change (RFAC) measured by
      cardiac magnetic resonance (CMR) allows the non-invasive localization and
      quantification of the degree of myocardial infarction (MI), and could be applied
      to assess the effectiveness of pharmacological or regenerative therapies. Here we
      investigate the ability of RFAC to identify regional dysfunction and discriminate
      the effect of pharmacological treatment with valsartan, a selective antagonist of
      angiotensin II type 1 receptor, in a model of MI. METHODS AND RESULTS: C57BL/6N
      mice, undergoing coronary artery ligation, were divided into two groups:
      untreated (MI) or treated with valsartan (MI+Val). Sham-operated mice were used
      as a control. Cardiac dimensions and function were assessed at baseline, 24
      hours, 1 and 4 weeks post surgery by CMR and echocardiography. At sacrifice
      histology and whole-genome gene expression profiling were performed. RFAC was
      able to detect significant differences between treatment groups whereas the
      global ejection fraction was not. RFAC showed greater loss of regional
      contraction in remote non-infarcted myocardium in MI group than in MI+Val group.
      Consistently, in the same region MI+Val mice showed reduced myocyte hypertrophy,
      fibroblast proliferation, and fibrosis and modulation of target genes; in
      addition, left atrium volumes, appendage length and duct contraction were
      preserved. CONCLUSION: In this study, RFAC effectively estimated the degree of
      systolic dysfunction and discriminated the regions preserved by pharmacological
      treatment. RFAC index is a promising tool to monitor changes in LV contraction
      and to assess the effectiveness of therapeutic regimens in clinical settings.

PMID- 26291975
TI  - Defect-Induced Conical Intersections Promote Nonradiative Recombination.
AB  - We apply multireference electronic structure calculations to demonstrate the
      presence of conical intersections between the ground and the first excited
      electronic states of three silicon nanocrystals containing defects characteristic
      of the oxidized silicon surface. These intersections are accessible upon
      excitation at visible wavelengths and are predicted to facilitate nonradiative
      recombination with a rate that increases with decreasing particle size. This work
      illustrates a new framework for identifying defects responsible for nonradiative
      recombination. 

PMID- 26291976
TI  - Plasma Homocysteine, Vitamin B12 and Folate Levels in Multiple System Atrophy: A
      Case-Control Study.
AB  - BACKGROUND: Multiple system atrophy (MSA) is a neurodegenerative disease, and its
      pathological hallmark is the accumulation of alpha-synuclein proteins.
      Homocysteine (Hcy) is an intermediate amino acid generated during the metabolism
      of methionine. Hcy may contribute to the pathogenesis of neurodegenerative
      disorders. Vitamin B12 and folate are cofactors necessary for the methylation of
      homocysteine. METHODS: This study compared the levels of serum Hcy, vitamin B12
      and folate in patients with MSA with those in healthy people to reveal the
      possible association between MSA and plasma levels of Hcy, vitamin B12 and
      folate. We enrolled 161 patients with MSA and 161 healthy people in this study.
      The association between MSA and the levels of Hcy, vitamin B12 and folate were
      analyzed using binary logistic regression. RESULTS: The mean level of Hcy in
      patients with MSA was significantly higher than that in healthy controls (16.23
      +/- 8.09 umol/l vs 14.04 +/- 4.25 umol/l, p < 0.05). After adjusting for age, sex
      and medical history, the odds ratio for Hcy was 1.07 (95% CI = 1.01-1.13, p <
      0.05) for patients with MSA. Vitamin B12 and folate levels were not significantly
      different between patients with MSA and controls. CONCLUSION: Our data suggest
      that higher levels of Hcy may be associated with an increased risk for MSA.

PMID- 26291977
TI  - Functionalized graphene oxide-based thermosensitive hydrogel for magnetic
      hyperthermia therapy on tumors.
AB  - A novel locally injectable, biodegradable, and thermo-sensitive hydrogel made
      from chitosan and beta-glycerophosphate salt was prepared. It incorporated
      polyethylenimine (PEI)-modified super-paramagnetic graphene oxide (GO/IONP/PEI)
      as a form of minimally invasive treatment of cancer lesions by magnetically
      induced local hyperthermia. Doxorubicin (DOX) was mixed into the hydrogel which
      was pre-loaded on GO/IONP/PEI to create a drug delivery system DOX-GO/IONP/PEI
      gel. In addition to the evaluation of in vitro and in vivo antitumor activities,
      the physicochemical properties, magnetic properties and DOX release profile of
      the DOX-GO/IONP/PEI-gel were determined. The aqueous solution of the hydrogel
      showed a sol-gel transition behavior depending on temperature changes.
      Magnetization loops indicated the super-paramagnetic properties of GO/IONP/PEI.
      Compared with free DOX, DOX-GO/IONP/PEI could efficiently pass through cell
      membranes, leading to more apoptosis and demonstrating higher antitumor efficacy
      on MCF-7 cells in vitro. Furthermore, DOX-GO/IONP/PEI-gel intratumorally injected
      (i.t.) showed high antitumor efficacy on tumor-bearing mice in vivo, with no
      obvious toxicity. The antitumor efficacy was higher when combined with an
      alternating magnetic field (AMF), showing that DOX-GO/IONP/PEI-gel under AMF has
      great potential for cancer magnetic hyperthermia therapy. 

PMID- 26291978
TI  - Effect of Traditional Chinese Exercise on Gait and Balance for Stroke: A
      Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: A systematic review is conducted to determine the effect of
      traditional Chinese exercise for patients with stroke. METHODS: Studies are
      obtained from PubMed, Embase, Cochrane Library, EBSCO, Web of Science, and CNKI.
      Only randomized controlled trials were left to evaluate the effects of
      traditional Chinese exercise for patients with stroke, and with no limits on
      study data or language. The primary outcome was the Berg balance score (BBS),
      Functional walking scale. And a random-effects model was used to calculate the
      pooled mean difference (MD) with 95% confidence interval (CI). RESULTS: A total
      of 9 studies on 820 participants conform to the inclusion criteria, whereas eight
      studies on 704 participants are used as data sources for the meta-analysis, all
      trials were published between 2004 and 2013. The BBS indicates that the efficacy
      of traditional Chinese exercise on balance of patients with stroke is better than
      that of other training or no training in short term [MD (95%CI) = 11.85 [5.41,
      18.30], P < 0.00001]. And the short physical performance battery, Functional
      walking scale, limit of stability were observed significant differences on
      balance (p<0.05) and gait (p<0.05) between traditional Chinese exercise and other
      exercises or no exercise. In addition, there is an article showed that some other
      form (physiotherapy exercises focused on balance) significantly improved balance
      ability for stroke patients compared to tai chi chuan practice (Berg test = 0.01,
      Romberg, and standing on one leg). CONCLUSION: In our meta analysis, the positive
      findings of this study suggest traditional Chinese exercise has beneficial
      effects on the balance ability in short term. However, we drew the conclusion
      according to the extreme heterogeneity, and evidence of better quality and from a
      larger sample size is required. Because of the inconsistent outcomes, there are
      short of enough good evidence for patients with stroke to prove the effects of
      traditional Chinese exercise on gait. SYSTEMATIC REVIEW REGISTRATION:
      http://www.crd.york.ac.uk/PROSPERO PROSPERO registration number: CRD42013006474.

PMID- 26291979
TI  - Heart Rate and Heart Rate Variability in Dairy Cows with Different Temperament
      and Behavioural Reactivity to Humans.
AB  - From the 1990s, extensive research was started on the physiological aspects of
      individual traits in animals. Previous research has established two extreme
      (proactive and reactive) coping styles in several animal species, but the means
      of reactivity with the autonomic nervous system (ANS) activity has not yet been
      investigated in cattle. The aim of this study was the characterization of cardiac
      autonomic activity under different conditions in cows with different individual
      characteristics. For this purpose, we investigated heart rate and ANS-related
      heart rate variability (HRV) parameters of dairy cows (N = 282) on smaller- and
      larger-scale farms grouped by (1) temperament and (2) behavioural reactivity to
      humans (BRH). Animals with high BRH scores were defined as impulsive, while
      animals with low BRH scores were defined as reserved. Cardiac parameters were
      calculated for undisturbed lying (baseline) and for milking bouts, the latter
      with the presence of an unfamiliar person (stressful situation). Sympathetic tone
      was higher, while vagal activity was lower in temperamental cows than in calm
      animals during rest both on smaller- and larger-scale farms. During milking, HRV
      parameters were indicative of a higher sympathetic and a lower vagal activity of
      temperamental cows as compared to calm ones in farms of both sizes. Basal heart
      rate did not differ between BRH groups either on smaller- or larger-scale farms.
      Differences between basal ANS activity of impulsive and reserved cows reflected a
      higher resting vagal and lower sympathetic activity of reserved animals compared
      to impulsive ones both on smaller- and larger-scale farms. There was no
      difference either in heart rate or in HRV parameters between groups during
      milking neither in smaller- nor in larger-scale farms. These two groupings
      allowed to draw possible parallels between personality and cardiac autonomic
      activity during both rest and milking in dairy cows. Heart rate and HRV seem to
      be useful for characterisation of physiological differences related to
      temperament and BRH. 

PMID- 26291980
TI  - Impact of Laboratory Practices on Interlaboratory Variability in Therapeutic Drug
      Monitoring of Immunosuppressive Drugs.
AB  - The immunosuppressants cyclosporine, tacrolimus, sirolimus, everolimus, and
      probably also mycophenolic acid require therapeutic drug monitoring (TDM)-guided
      dosing to ensure that blood concentrations are kept within the target range in
      transplant patients. Reliable, accurate, and precise test methods are therefore
      essential to effectively monitor levels and to make proper dose adjustments. Data
      from proficiency testing programs have shown substantial interlaboratory
      variability. Only few attempts have been made to study the underlying causes. The
      aim of this study was to systematically document current practices used for
      immunosuppressant drug TDM in clinical laboratories and identify methodological
      and practice differences, which may cause the variability observed among
      laboratories. Data collection was primarily conducted by a structured Web-based
      survey. Invitations to participate in the survey were distributed to clinical
      laboratories providing immunosuppressant drug TDM. Surveys were completed by 76
      laboratories in 14 countries. The results of our survey suggest that there are 3
      main reasons for interlaboratory variability: (1) lack of standardization of
      laboratory procedures and workflows starting with sample collection and handling,
      (2) lack of use of appropriate reference materials (eg, isotope-labeled internal
      standards for liquid chromatography-tandem mass spectroscopy), and (3) poor
      compliance with internationally accepted good laboratory practice guidelines (eg,
      related to quality control, quality assurance, validation, training of
      personnel). The results of the survey also suggest that interlaboratory
      variability is a multifactorial problem. Technical-level consensus on laboratory
      operational procedures, quality systems, and personnel training will be of great
      importance to improve quality and interlaboratory comparability.

PMID- 26291981
TI  - Identification of MMP-9 as a biomarker for detecting progression of chronic
      obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is a complex immunological disease
      with multiple pathological features that is primarily induced by smoking together
      with additional genetic risk factors. COPD is frequently underdiagnosed; forced
      expiratory volume in the first second (FEV1) is considered to be the main
      diagnostic measure for COPD, yet it is insufficiently sensitive to monitor
      disease progression. Biomarkers capable of monitoring COPD progression and
      severity are needed. In this report, we evaluated matrix metalloproteinase-9 (MMP
      9) as an early marker for the detection and staging of COPD, by assessing the
      mRNA levels of MMP-9 in peripheral blood samples collected from 22 COPD patients,
      6 asymptomatic smokers, and 5 healthy controls. Our results demonstrate that the
      mRNA levels of MMP-9 increased more than two-fold in severe COPD relative to non
      COPD smokers or moderate COPD groups. Moreover, in the very severe COPD group,
      MMP-9 mRNA levels showed a 4-fold increase relative to the non-COPD smokers or
      the moderate COPD groups, while there was a mild increase (~40%) when compared to
      the severe COPD group. Taken together, our results suggest that MMP-9 serves as a
      biomarker for the grade and severity of COPD. 

PMID- 26291982
TI  - Androgen Receptor Gene Polymorphism, Aggression, and Reproduction in Tanzanian
      Foragers and Pastoralists.
AB  - The androgen receptor (AR) gene polymorphism in humans is linked to aggression
      and may also be linked to reproduction. Here we report associations between AR
      gene polymorphism and aggression and reproduction in two small-scale societies in
      northern Tanzania (Africa)--the Hadza (monogamous foragers) and the Datoga
      (polygynous pastoralists). We secured self-reports of aggression and assessed
      genetic polymorphism of the number of CAG repeats for the AR gene for 210 Hadza
      men and 229 Datoga men (aged 17-70 years). We conducted structural equation
      modeling to identify links between AR gene polymorphism, aggression, and number
      of children born, and included age and ethnicity as covariates. Fewer AR CAG
      repeats predicted greater aggression, and Datoga men reported more aggression
      than did Hadza men. In addition, aggression mediated the identified negative
      relationship between CAG repeats and number of children born.

PMID- 26291984
TI  - Sport Engagement by Accelerometry under Field Conditions in German Adolescents:
      Results from GINIPlus.
AB  - INTRODUCTION: Sporting activities differ in their ability to promote moderate-to
      vigorous physical activity (MVPA). To assess adolescents' engagement in sport
      under field conditions we used accelerometers to measure their MVPA levels during
      sport. We pay special attention to differences between team and individual sport
      and between common sports. METHODS: Diary data and 7-day accelerometry from 1054
      Germans ages 15-17 were combined to measure physical activity. 1373 diaried
      episodes of more than 40 common sports were identified from 626 participants and
      grouped into team and individual sport. We modeled the effect of team and
      individual sport, and described levels of MVPA and episodes of no MVPA for all
      recorded sports. RESULTS: German boys and girls averaged 43 (SD 21) and 37 (SD
      24) minutes MVPA per day. Boys got 2.2 times as much MVPA per minute during team
      compared to individual sport (p<0.0001) but there was no significant difference
      for girls. Percent of time spent in MVPA during sport ranged from 6% for weight
      training to 74% for jogging, with individual sports averaging 10-30% and team
      sports 30-50%. 11% of sport episodes had no MVPA: half of episodes of cycling, 5%
      of jogging, and none for tennis or badminton. An episode of individual sport was
      17 times more likely to have no MVPA than an episode of team sport (p<0.0001).
      CONCLUSION: Under field condition, adolescents were active for only a fraction of
      diaried sporting time. As measured by accelerometry, individual sport often
      produced no MVPA. Characteristics of the sport, such as team vs. individual, were
      more predictive of MVPA than were characteristics of the participant, such as
      background activity levels.

PMID- 26291983
TI  - beta-Glucans (Saccharomyces cereviseae) Reduce Glucose Levels and Attenuate
      Alveolar Bone Loss in Diabetic Rats with Periodontal Disease.
AB  - The objective of this study was to assess the effects of oral ingestion of beta
      glucans isolated from Saccharomyces cereviseae on the metabolic profile,
      expression of gingival inflammatory markers and amount of alveolar bone loss in
      diabetic rats with periodontal disease. Diabetes mellitus was induced in 48
      Wistar rats by intraperitoneal injection of streptozotocin (80 mg/kg). After
      confirming the diabetes diagnosis, the animals were treated with beta-glucans (by
      gavage) for 28 days. On the 14th day of this period, periodontal disease was
      induced using a ligature protocol. beta-glucans reduced the amount of alveolar
      bone loss in animals with periodontal disease in both the diabetic and non
      diabetic groups (p < 0.05). beta-glucans reduced blood glucose, cholesterol and
      triacylglycerol levels in diabetic animals, both with and without periodontal
      disease (p < 0.05). Furthermore, treatment with beta-glucans reduced the
      expression of cyclooxygenase-2 and receptor activator of nuclear factor kappa-B
      ligand and increased osteoprotegerin expression in animals with diabetes and
      periodontal disease (p < 0.05). It was concluded that treatment with beta-glucans
      has beneficial metabolic and periodontal effects in diabetic rats with
      periodontal disease. 

PMID- 26291985
TI  - Supersaturation-Limited and Unlimited Phase Spaces Compete to Produce Maximal
      Amyloid Fibrillation near the Critical Micelle Concentration of Sodium Dodecyl
      Sulfate.
AB  - Although various natural and synthetic compounds have been shown to accelerate or
      inhibit the formation of amyloid fibrils, the mechanisms by which they achieve
      these adverse effects in a concentration-dependent manner currently remain
      unclear. Sodium dodecyl sulfate (SDS), one of the compounds that has adverse
      effects on fibrillation, is the most intensively studied. Here we examined the
      effects of a series of detergents including SDS on the amyloid fibrillation of
      beta2-microglobulin at pH 7.0, a protein responsible for dialysis-related
      amyloidosis. In all the detergents examined (i.e., SDS, sodium decyl sulfate,
      sodium octyl sulfate, and sodium deoxycholate), amyloid fibrillation was
      accelerated and inhibited at concentrations near the critical micelle
      concentration (CMC) and higher than CMC, respectively. The most stable
      conformation changed from monomers with a beta-structure to amyloid fibrils with
      a beta-structure and then to alpha-helical complexes with micelles with an
      increase in detergent concentrations. These results suggest that competition
      between supersaturation-limited fibrillation and unlimited mixed micelle
      formation between proteins and micelles underlies the detergent concentration
      dependent complexity of amyloid fibrillation. 

PMID- 26291986
TI  - Follow-up of Contacts of Middle East Respiratory Syndrome Coronavirus-Infected
      Returning Travelers, the Netherlands, 2014.
AB  - Notification of 2 imported cases of infection with Middle East respiratory
      syndrome coronavirus in the Netherlands triggered comprehensive monitoring of
      contacts. Observed low rates of virus transmission and the psychological effect
      of contact monitoring indicate that thoughtful assessment of close contacts is
      prudent and must be guided by clinical and epidemiologic risk factors. 

PMID- 26291987
TI  - Significant role of Psf3 expression in non-small-cell lung cancer.
AB  - The GINS complex associates with cell division cycle (Cdc) protein 45 and mini
      chromosome maintenance (Mcm) proteins 2-7 to form the Cdc45-Mcm-GINS (CMG)
      complex, which is essential for DNA duplication. One member of the GINS complex
      is Psf3. We previously found that increased Psf3 expression was strongly
      associated with poor survival in lung adenocarcinoma. Here, we investigated the
      role of Psf3 expression in non-small-cell lung cancer (NSCLC). We verified Psf3
      expression in human NSCLC tissues (180 patients) and cell lines.
      Immunohistochemical analysis revealed that the overexpression of Psf3 was
      significantly associated with vessel invasion (P = 0.016), lymphatic invasion (P
      = 0.002), and pleural invasion (P = 0.036). The overall survival rate in patients
      with Psf3 overexpression was significantly lower than that in patients without
      Psf3 overexpression (P = 0.006). Multivariate survival analysis revealed Psf3
      expression to be an independent risk factor for an unfavorable outcome (P =
      0.049). A proximal ligation assay showed interactions between Psf3 and other CMG
      components (such as Mcm2 and Cdc45) in both NSCLC specimens and cell lines,
      indicating that Psf3 acted as the CMG complex, which could lead to excessive
      proliferation. Knockdown of Psf3 inhibited the proliferation of both cell lines
      by delaying the S phase, which revealed that Psf3 played an important role in
      cancer proliferation. Thus, Psf3 acted as the CMG complex, promoting excessive
      proliferation. These results suggest that Psf3 inhibition might be a therapeutic
      target for NSCLC with Psf3 overexpression. 

PMID- 26291989
TI  - Patients with multiple sclerosis do not necessarily consume more alcohol or
      tobacco than the general population.
AB  - Purpose Recent papers suggest that patients with multiple sclerosis (MS) are
      prone to alcohol misuse. This may be due to the combination of a lifelong and
      disabling disease with a psychiatric profile typical of MS. The objective of the
      present study was to assess these findings in a culturally different population
      of patients with MS.Method The present case-control transversal study assessed
      168 patients with MS and 168 control subjects from Brazil.Results There were no
      evidence that patients with MS drank more alcohol or, smoked more than did
      controls. In fact, control subjects had a significantly higher alcohol
      consumption. The only trait associated to higher alcohol consumption was anxiety,
      both for patients and controls.Conclusion Unlike previous reports in the
      literature, patients with MS in our study did not drink or smoked more than a
      control population. 

PMID- 26291988
TI  - Species-Specific Serological Detection for Schistosomiasis by Serine Protease
      Inhibitor (SERPIN) in Multiplex Assay.
AB  - BACKGROUND: Both Schistosoma mansoni and Schistosoma haematobium cause
      schistosomiasis in sub-Saharan Africa. We assessed the diagnostic value of
      selected Schistosoma antigens for the development of a multiplex serological
      immunoassay for sero-epidemiological surveillance. METHODOLOGY/PRINCIPAL
      FINDINGS: Diagnostic ability of recombinant antigens from S. mansoni and S.
      haematobium was assessed by Luminex multiplex immunoassay using plasma from
      school children in two areas of Kenya, endemic for different species of
      schistosomiasis. S. mansoni serine protease inhibitor (SERPIN) and Sm-RP26 showed
      significantly higher reactivity to patient plasma as compared to the control
      group. Sm-Filamin, Sm-GAPDH, Sm-GST, Sm-LAP1, Sm-LAP2, Sm-Sm31, Sm-Sm32 and Sm
      Tropomyosin did not show difference in reactivity between S. mansoni infected and
      uninfected pupils. Sm-RP26 was cross-reactive to plasma from S. haematobium
      patients, whereas Sm-SERPIN was species-specific. Sh-SEPRIN was partially cross
      reactive to S. mansoni infected patients. ROC analysis for Sm-RP26, Sm-SERPIN and
      Sh-SERPIN showed AUC values of 0.833, 0.888 and 0.947, respectively. Using
      Spearman's rank correlation coefficient analysis, we also found significant
      positive correlation between the number of excreted eggs and median fluorescence
      intensity (MFI) from the multiplex immunoassays for Sm-SERPIN (rho = 0.430, p
      value = 0.003) and Sh-SERPIN (rho = 0.433, p-value = 0.006).
      CONCLUSIONS/SIGNIFICANCE: Sm-SERPIN is a promising species-specific diagnostic
      antigen. Sh-SEPRIN was partially cross-reactive to S. mansoni infected patients.
      SERPINs showed correlation with the number of excreted eggs. These indicate
      prospects for inclusion of SERPINs in the multiplex serological immunoassay
      system.

PMID- 26291991
TI  - Non-progressive cerebellar ataxia and previous undetermined acute cerebellar
      injury: a mysterious clinical condition.
AB  - Cerebellar ataxias represent a wide group of neurological diseases secondary to
      dysfunctions of cerebellum or its associated pathways, rarely coursing with acute
      onset acquired etiologies and chronic non-progressive presentation. We evaluated
      patients with acquired non-progressive cerebellar ataxia that presented previous
      acute or subacute onset. Clinical and neuroimaging characterization of adult
      patients with acquired non-progressive ataxia were performed. Five patients were
      identified with the phenotype of acquired non-progressive ataxia. Most patients
      presented with a juvenile to adult-onset acute to subacute appendicular and
      truncal cerebellar ataxia with mild to moderate cerebellar or
      olivopontocerebellar atrophy. Establishing the etiology of the acute triggering
      events of such ataxias is complex. Non-progressive ataxia in adults must be
      distinguished from hereditary ataxias. 

PMID- 26291992
TI  - Chronic stage of Marchiafava-Bignami disease.

PMID- 26291994
TI  - Analysis of cerebrospinal fluid in racemose form of neurocysticercosis.
AB  - The present work aimed to evaluate the pattern of CSF alterations in patients
      diagnosed with neurocysticercosis (NCC) in racemose form.Method This is a
      retrospective cohort study of patients with diagnosis of NCC in racemose form.
      CSF samples from 26 patients were analyzed. After patient-chart analysis was
      performed descriptive analysis of case studies and comparison between sexes in
      relation to variables were obtained with CSF by Mann-Whitney and Student's t
      tests.Results The sexes did not differ statistically when compared to pleocytosis
      in CSF. Eosinophils were present in 31% in samples while the ELISA test presented
      80% sensitivity in this case series. Of the patient total, 24 presented a
      meningitis pattern with lymphocytic predominance.Conclusion There was no
      difference in inflammatory pattern between the sexes, with predominance of
      lymphocytic meningitis and 80% sensitivity by ELISA test of CSF patients with
      racemose form of NCC. 

PMID- 26291995
TI  - OnabotulinumtoxinA for trigeminal neuralgia: a review of the available data.
AB  - Trigeminal neuralgia (TN) patients may develop side effects from centrally acting
      drugs, have contraindications for neurosurgical procedures, or experience relapse
      during conventional therapies. OnabotulinumtoxinA (BoNT/A) has been reported to
      be effective for TN, although this finding has been challenged. An overview of
      the available evidence based on a narrative/qualitative analysis of the
      literature is presented. About 90% of patients who receive BoNT/A show an
      improvement, a higher figure than that reported for the placebo effect of BoNT/A
      for other headaches. Tolerability of BoNT/A is good, and its few side-effects are
      transient. The articles reviewed were mainly case reports, case series and open
      label trials; however, randomized controlled trials have endorsed the efficacy of
      BoNT/A for TN. This evidence, together with a better understanding of the
      analgesic mechanisms of BoNT/A and its proven efficacy in treating other pain
      syndromes, supports the use of this toxin as a therapeutic option for TN. 

PMID- 26291996
TI  - Ultrasensitive photoelectrochemical biosensing of multiple biomarkers on a single
      electrode by a light addressing strategy.
AB  - Ultrasensitive multiplexed detection of biomarkers on a single electrode is
      usually a great challenge for electrochemical sensors. Here, a light addressable
      photoelectrochemical sensor (LAPECS) for the sensitive detection of multiple DNA
      biomarkers on a single electrode was reported. The sensor was constructed through
      four steps: (1) immobilization of capture DNA (C-DNA) of different targets on
      different areas of a single large-sized gold film electrode, (2) recognition of
      each target DNA (T-DNA) and the corresponding biotin-labeled probe DNA (P-DNA)
      through hybridization, (3) reaction of the biotin-labeled probe DNA with a
      streptavidin-labeled all-carbon PEC bioprobe, and (4) PEC detection of multiple
      DNA targets one by one via a light addressing strategy. Through this principle,
      the LAPECS can achieve ultrasensitive detection of three DNA sequences related to
      hepatitis B (HBV), hepatitis C (HCV) and human immunodeficiency (HIV) viruses
      with a similar wide calibration range of 1.0 pM ~ 0.01 MUM and a low detection
      limit of 0.7 pM by using one kind of PEC bioprobe. Moreover, the detection
      throughput of LAPECS may be conveniently expanded by simply enlarging the size of
      the substrate electrode or reducing the size of the sensing arrays and the light
      beam. The present work thus demonstrates the promising applications of LAPECS in
      developing portable, sensitive, high-throughput, and cost-effective biosensing
      systems. 

PMID- 26291997
TI  - Towards a new model of attentional biases in the development, maintenance, and
      management of pain.
AB  - Individuals with chronic pain demonstrate attentional biases (ABs) towards pain
      related stimuli. However, the clinical importance of these biases is yet to be
      determined and a sound theoretical model for explaining the role of ABs in the
      development and maintenance of pain is lacking. Within this article, we (1)
      systematically review prospective and experimental research exploring ABs and
      pain outcomes in light of current theoretical models and (2) propose a
      theoretical framework for understanding AB in pain. Across prospective research,
      an attentional pattern of vigilance-avoidance was observed. Interventions
      targeting ABs were less consistent; however, there were promising findings among
      studies that found attentional training effects, particularly for laboratory
      research. The proposed Threat Interpretation Model suggests a relationship
      between threat, interpretation, and stimuli in determining attentional processes,
      which while tentative generates important testable predictions regarding the role
      of attention in pain and builds on previous theoretical and empirical work in
      this area. 

PMID- 26291998
TI  - Do genetic factors improve prediction of postherniotomy pain?

PMID- 26291999
TI  - Reply: To PMID 25599448.

PMID- 26292000
TI  - Diagnostic requirements are necessary before dry needling in the treatment of
      chronic pain.

PMID- 26292001
TI  - Reply: To PMID 25790454.

PMID- 26292002
TI  - Concern regarding use of the term "nonhuman animals" in the article "Ontogeny and
      phylogeny of facial expression of pain".

PMID- 26292003
TI  - Reply: To PMID 25887392.

PMID- 26292004
TI  - Correction to "Grazing Incidence Small-Angle X-ray Scattering Analysis of Initial
      Growth of Planar Organic Molecules Affected by Substrate Surface Energy".

PMID- 26292005
TI  - Tracing Molecular Propagation in Dextran Solutions by Pulsed Field Gradient NMR.
AB  - We have exploited the pulsed field gradient (PFG) technique of NMR to measure
      molecular diffusion in aqueous solutions of a mixture of dextran molecules. From
      detailed studies by fluorescence correlation spectroscopy (FCS), the lighter
      component of such mixtures is known to undergo subdiffusion, up to diffusion path
      lengths on the order of 0.5 MUm. Our studies provide clear evidence of a
      crossover to normal diffusion for diffusion path lengths from this range up to
      about 1 MUm. 

PMID- 26292006
TI  - Atomically Resolved Site-Isolated Catalyst on MgO: Mononuclear Osmium Dicarbonyls
      formed from Os3(CO)12.
AB  - Supported triosmium clusters, formed from Os3(CO)12 on MgO, were treated in
      helium at 548 K for 2 h, causing fragmentation of the cluster frame and the
      formation of mononuclear osmium dicarbonyls. The cluster breakup and the
      resultant fragmented species were characterized by infrared and X-ray absorption
      spectroscopies, and the fragmented species were imaged by scanning transmission
      electron microscopy. The spectra identify the surface osmium complexes as
      Os(CO)2{Osupport}n (n = 3 or 4) (where the braces denote support surface atoms).
      The images show site-isolated Os atoms in mononuclear osmium species on MgO. The
      intensity analysis on the images of the MgO(110) face showed that the Os atoms
      were located atop Mg columns. This information led to a model of the Os(CO)2 on
      MgO(110), with the distances approximated as those determined by EXAFS
      spectroscopy, which are an average over the whole MgO surface; the results imply
      that these complexes were located at Mg vacancies. 

PMID- 26292007
TI  - Electrochemical Synthesis of p-Type CuFeO2 Electrodes for Use in a
      Photoelectrochemical Cell.
AB  - A new electrodeposition route was developed to prepare p-type CuFeO2 as a thin
      film-type electrode for use as a photocathode in a solar water splitting cell.
      The resulting p-CuFeO2 film has a bandgap energy of ca. 1.55 eV, with its
      conduction band edge located at a more negative potential than the reduction
      potential of water. Various photoelectrochemical properties of the p-CuFeO2
      electrode were investigated, and its photoelectrochemical hydrogen production in
      1 M NaOH solution was confirmed by gas chromatography. The incident photon-to
      current conversion efficiency plot confirmed that p-CuFeO2 has the ability to
      utilize the entire range of visible light. 

PMID- 26292008
TI  - Exciton Energy and Charge Transfer in Porphyrin Aggregate/Semiconductor (TiO2)
      Composites.
AB  - A porphyrin aggregate is reported that exhibits novel exciton state properties
      for light-harvesting applications. This porphyrin aggregate enables control of
      energy dissipation of coherent excited states by changing the self-assembly
      pattern. New exciton spectral features create a new route of energy transfer in
      this porphyrin aggregate. The kinetic model of exciton state decay is addressed
      in this Perspective by reporting steady-state and transient emission and
      absorption studies of porphyrin J- and H-aggregates. The porphyrin J-aggregate
      emerges with better spectral coverage and exciton dynamics, which are suitable
      for light-harvesting antenna functions. This motif is explored in a
      photosensitization study of TiO2 semiconductor materials. The transient
      absorption studies show that the J-aggregate improves the photoinduced charge
      separation at the porphyrin/TiO2 interface. The higher charge separation is
      attributed to exciton-coupled charge-transfer processes in porphyrin J
      aggregate/TiO2 hybrid materials. It represents the potential of porphyrin
      aggregates in biomimetic artificial antenna activity. 

PMID- 26292009
TI  - Quantum-Dot-Sensitized Solar Cells: Effect of Nanostructured TiO2 Morphologies on
      Photovoltaic Properties.
AB  - There is a great deal of interest in dye-sensitized solar cells (DSCs) fabricated
      with nanostructured TiO2 electrodes. Many different dye molecules have been
      designed and synthesized to achieve high photovoltaic conversion efficiency.
      Recently, as an alternative to organic dyes, semiconductor quantum dots (QDs)
      have been studied for their light-harvesting capability compared with other
      sensitizers. Accordingly, an attractive configuration to exploit these
      fascinating properties of semiconductor QDs is the quantum-dot-sensitized solar
      cell (QDSC) due to their high photoactivity, process realization, and low cost of
      production. The morphology of TiO2 electrodes included with surface orientation
      is important for satisfactory assembly of QDSCs in order to improve the
      efficiency. Breakthroughs allowing an increase in efficiency will advance on two
      areas of electrode morphology control, namely, (A) TiO2 nanotube electrodes and
      (B) inverse opal TiO2 electrodes. 

PMID- 26292010
TI  - Structure Revealing H/D Exchange with Co-Adsorbed Hydrogen and Water on Gold.
AB  - A fundamental understanding of the interactions between coadsorbed water and
      hydrogen on metallic surfaces is critical to many chemical processes including
      catalysis and electrochemistry. Here, we report on the strong and intricate
      interactions between coadsorbed H/D and water on the close-packed (111) surface
      of gold. Deuterium isotopic labeling shows H/D exchange in H-D2O and D-H2O
      systems, indicating water dissociation and suggesting a nonrandom scrambling
      process by revealing the origin of hydrogen evolution (from surface H atoms or
      from water molecules) during annealing. In this reaction, the protonation of the
      H-bonding ice network (i.e., the formation of (H2O)nH(+)) is energetically
      favorable and is responsible for water dissociation. Density functional theory
      (DFT) modeling suggests that the thermodynamics and structure of the protonated
      clusters are predominant factors for yielding the traceable H2 desorption
      features from the surface interaction with H atoms, providing insights into
      reaction mechanisms. 

PMID- 26292011
TI  - Automated Exploration of Photolytic Channels of HCOOH: Conformational Memory via
      Excited-State Roaming.
AB  - To elucidate the photodissociation mechanism of HCOOH, we systematically explored
      reaction pathways starting from the first excited singlet state (S1) by using
      automated reaction path search methods. All critical points, that is, minima,
      transition states, minimum energy conical intersections, and minima on seam of
      crossing, for the S0, T1, and S1 potential energy surfaces (PESs) obtained in the
      present search were optimized at the CASPT2 level. The structure list obtained by
      the search explained all experimentally reported photolytic channels. A new
      mechanism for the previously suggested but unexplained conformational memory in
      the 193 nm photolysis is proposed, which involves two steps: partial dissociation
      and succeeding roaming of one of H atoms on the S1 PES, followed by
      intramolecular recombination on the S0 PES after radiationless transition through
      a conical intersection at a partially dissociated geometry. This is partially
      similar to the excited-state roaming recently discovered for the NO3 radical. 

PMID- 26292012
TI  - Bulk Heterojunction versus Diffused Bilayer: The Role of Device Geometry in
      Solution p-Doped Polymer-Based Solar Cells.
AB  - We exploit the effect of molecular p-type doping of P3HT in diffused bilayer (DB)
      polymer solar cells. In this alternative device geometry, the p-doping is
      accomplished in solution by blending the F4-TCNQ with P3HT. The p-doping both
      increases the film conductivity and reduces the potential barrier at the
      interface with the electrode. This results in an excellent power conversion
      efficiency of 4.02%, which is an improvement of ~48% over the p-doped standard
      bulk heterojunction (BHJ) device. Combined VOC-light intensity dependence
      measurements and Kelvin probe force microscopy reveal that the DB device
      configuration is particularly advantageous, if compared to the conventional BHJ,
      because it enables optimization of the donor and acceptor layers independently to
      minimize the effect of trapping and to fully exploit the improved transport
      properties. 

PMID- 26292013
TI  - Calculating the Lifetimes of Metastable States with Complex Density Functional
      Theory.
AB  - Among other applications, complex absorbing potentials (CAPs) have proven to be
      useful tools in the theory of metastable states. They facilitate the conversion
      of unbound states of a finite lifetime into normalized bound states with a
      complex energy. Adding CAPs to a conventional Hamiltonian turns it into a non
      Hermitian operator. Recently, we introduced a complex density functional theory
      (CODFT) that extends the Kohn-Sham method to the realm of non-Hermitian systems.
      Here, we combine CAPs with CODFT and present the first application of CODFT to
      metastable systems. In particular, we consider the negative ions of the beryllium
      atom and the nitrogen molecule. Using conventional exchange-correlation
      functionals as functionals of a complex density, the resonance positions and the
      resonance lifetimes are obtained, and they are in line with the findings of other
      studies. 

PMID- 26292014
TI  - Contribution of Femtosecond Laser Spectroscopy to the Development of Advanced
      Optoelectronic Nanomaterials.
AB  - Femtosecond laser spectroscopy has now been a powerful technique for over a
      decade to investigate charge carrier dynamics in nanoscale optoelectronic systems
      with a temporal resolution of 100 fs (10(-13) s) or better. Both transient
      absorption and time-resolved photoluminescence spectroscopy are now popular
      spectroscopic techniques, which are well-established and provide direct insight
      into the charge carrier dynamics of nanomaterials. In this Perspective, we focus
      mainly on the developments with regard to studies of semiconductor
      nanostructures. Controlling the charge carrier dynamics, including hot carrier
      relaxation, trapping, interfacial carrier transfer, carrier multiplication, and
      recombination, is essential for successful energy conversion or photocatalysis,
      to name two major optoelectronic applications. We will show how femtosecond laser
      spectroscopy evolved into techniques that unveil the dynamic charge carrier
      properties of semiconductor nanomaterials toward heterostructures and complex
      nanoarchitectures and that femtosecond time-resolved laser spectroscopy can shine
      light on the path to novel optoelectronic structures and emergent optoelectronic
      technologies. 

PMID- 26292015
TI  - Sulfated Graphene Oxide as a Hole-Extraction Layer in High-Performance Polymer
      Solar Cells.
AB  - In this study, we have rationally designed and successfully developed sulfated
      graphene oxide (GO-OSO3H) with -OSO3H groups attached to the carbon basal plane
      of reduced GO surrounded with edge-functionalized -COOH groups. The resultant GO
      OSO3H is demonstrated to be an excellent hole extraction layer (HEL) for polymer
      solar cells (PSCs) because of its proper work function for Ohmic contact with the
      donor polymer, its reduced basal plane for improving conductivity, and its 
      OSO3H/-COOH groups for enhancing solubility for solution processing. Compared
      with that of GO, the much improved conductivity of GO-OSO3H (1.3 S m(-1) vs 0.004
      S m(-1)) leads to greatly improved fill factor (0.71 vs 0.58) and power
      conversion efficiency (4.37% vs 3.34%) of the resulting PSC devices. Moreover,
      the device performance of GO-OSO3H is among the best reported for intensively
      studied poly(3-hexylthiophene):[6,6]-phenyl-C61 butyric acid methyl ester
      (P3HT:PCBM) devices. Our results imply that judiciously functionalized graphene
      materials can be used to replace existing HEL materials for specific device
      applications with outstanding performance. 

PMID- 26292016
TI  - The Journal of Physical Chemistry Letters, The FIRST Impact.

PMID- 26292017
TI  - Improving Accuracy of Influenza-Associated Hospitalization Rate Estimates.
AB  - Diagnostic test sensitivity affects rate estimates for laboratory-confirmed
      influenza-associated hospitalizations. We used data from FluSurv-NET, a national
      population-based surveillance system for laboratory-confirmed influenza
      hospitalizations, to capture diagnostic test type by patient age and influenza
      season. We calculated observed rates by age group and adjusted rates by test
      sensitivity. Test sensitivity was lowest in adults >65 years of age. For all
      ages, reverse transcription PCR was the most sensitive test, and use increased
      from <10% during 2003-2008 to ~70% during 2009-2013. Observed hospitalization
      rates per 100,000 persons varied by season: 7.3-50.5 for children <18 years of
      age, 3.0-30.3 for adults 18-64 years, and 13.6-181.8 for adults >65 years. After
      2009, hospitalization rates adjusted by test sensitivity were ~15% higher for
      children <18 years, ~20% higher for adults 18-64 years, and ~55% for adults >65
      years of age. Test sensitivity adjustments improve the accuracy of
      hospitalization rate estimates. 

PMID- 26292018
TI  - Development of a Surface Plasmon Resonance Assay for the Characterization of
      Small-Molecule Binding Kinetics and Mechanism of Binding to Kynurenine 3
      Monooxygenase.
AB  - Kynurenine 3-monooxygenase (KMO), a pivotal enzyme in the kynurenine pathway, was
      identified as a potential therapeutic target for treating neurodegenerative and
      psychiatric disorders. In this article, we describe a surface plasmon resonance
      (SPR) assay that delivers both kinetics and the mechanism of binding (MoB) data,
      enabling a detailed characterization of KMO inhibitors for the enzyme in real
      time. SPR assay development included optimization of the protein construct and
      the buffer conditions. The stability and inhibitor binding activity of the
      immobilized KMO were significantly improved when the experiments were performed
      at 10 degrees C using a buffer containing 0.05% n-dodecyl-beta-d-maltoside (DDM)
      as the detergent. The KD values of the known KMO inhibitors (UPF648 and RO61
      8048) from the SPR assay were in good accordance with the biochemical LC/MS/MS
      assay. Also, the SPR assay was able to differentiate the binding kinetics (k(a)
      and k(d)) of the selected unknown KMO inhibitors. For example, the inhibitors
      that showed comparable IC50 values in the LC/MS/MS assay displayed differences in
      their residence time (tau = 1/k(d)) in the SPR assay. To better define the MoB of
      the inhibitors to KMO, an SPR-based competition assay was developed, which
      demonstrated that both UPF648 and RO61-8048 bound to the substrate-binding site.
      These results demonstrate the potential of the SPR assay for characterizing the
      affinity, the kinetics, and the MoB profiles of the KMO inhibitors.

PMID- 26292019
TI  - Manual lateralization in macaques: handedness, target laterality and task
      complexity.
AB  - Non-human primates represent models to understand the evolution of handedness in
      humans. Despite several researches have been investigating non-human primates
      handedness, few studies examined the relationship between target position, hand
      preference and task complexity. This study aimed at investigating macaque
      handedness in relation to target laterality and tastiness, as well as task
      complexity. Seven pig-tailed macaques (Macaca nemestrina) were involved in three
      different "two alternative choice" tests: one low-level task and two high-level
      tasks (HLTs). During the first and the third tests macaques could select a
      preferred food and a non-preferred food, whereas by modifying the design of the
      second test, macaques were presented with no-difference alternative per trial.
      Furthermore, a simple-reaching test was administered to assess hand preference in
      a social context. Macaques showed hand preference at individual level both in
      simple and complex tasks, but not in the simple-reaching test. Moreover, target
      position seemed to affect hand preference in retrieving an object in the low
      level task, but not in the HLT. Additionally, individual hand preference seemed
      to be affected from the tastiness of the item to be retrieved. The results
      suggest that both target laterality and individual motivation might influence
      hand preference of macaques, especially in simple tasks. 

PMID- 26292020
TI  - High power organic cathodes using thin films of electropolymerized benzidine
      polymers.
AB  - Thin films of benzidine polymers were electrochemically deposited directly onto
      conductive substrates by oxidative coupling of di- and trianilinoalkane monomers.
      The electropolymerization and electrochemical properties of the polymers were
      optimized by varying the alkyl linker. Polymer films exhibited two reversible one
      electron transfers at high potentials (>3.3 V vs. Li/Li(+)) and maintained
      discharge capacities in excess of 150 mA h g(-1) even when discharged in under 4
      seconds. 

PMID- 26292021
TI  - Biostimulation by Glycerol Phosphate to Precipitate Recalcitrant Uranium(IV)
      Phosphate.
AB  - Stimulating the microbial reduction of aqueous uranium(VI) to insoluble U(IV) via
      electron donor addition has been proposed as a strategy to remediate uranium
      contaminated groundwater in situ. However, concerns have been raised regarding
      the longevity of microbially precipitated U(IV) in the subsurface, particularly
      given that it may become remobilized if the conditions change to become
      oxidizing. An alternative mechanism is to stimulate the precipitation of poorly
      soluble uranium phosphates via the addition of an organophosphate and promote the
      development of reducing conditions. Here, we selected a sediment sample from a
      U.K. nuclear site and stimulated the microbial community with glycerol phosphate
      under anaerobic conditions to assess whether uranium phosphate precipitation was
      a viable bioremediation strategy. Results showed that U(VI) was rapidly removed
      from solution and precipitated as a reduced crystalline U(IV) phosphate mineral
      similar to ningyoite. This mineral was considerably more recalcitrant to
      oxidative remobilization than the products of microbial U(VI) reduction. Bacteria
      closely related to Pelosinus species may have played a key role in uranium
      removal in these experiments. This work has implications for the stewardship of
      uranium-contaminated groundwater, with the formation of U(IV) phosphates
      potentially offering a more effective strategy for maintaining low concentrations
      of uranium in groundwater over long time periods. 

PMID- 26292022
TI  - A Metal- and Azide-Free Multicomponent Assembly toward Regioselective
      Construction of 1,5-Disubstituted 1,2,3-Triazoles.
AB  - The construction of 1,5-disubstituted 1,2,3-triazoles has been effected through
      the cascade dual C-N bond formation, N-N bond formation and an acyl migration
      based C-C bond formation via the three-component reactions of enaminones,
      tosylhydrazine and primary amines. This metal- and azide-free, regioselective
      synthetic method proceeds in the presence of only molecular iodine. 

PMID- 26292023
TI  - "Wild cannabis": A review of the traditional use and phytochemistry of Leonotis
      leonurus.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Leonotis leonurus, locally commonly known as
      "wilde dagga" (=wild cannabis), is traditionally used as a decoction, both
      topically and orally, in the treatment of a wide variety of conditions such as
      haemorrhoids, eczema, skin rashes, boils, itching, muscular cramps, headache,
      epilepsy, chest infections, constipation, spider and snake bites. The dried
      leaves and flowers are also smoked to relieve epilepsy. The leaves and flowers
      are reported to produce a mild euphoric effect when smoked and have been said to
      have a similar, although less potent, psychoactive effect to cannabis. AIM OF THE
      REVIEW: To amalgamate the botanical aspects, ethnopharmacology, phytochemistry,
      biological activity, toxicity and commercial aspects of the scientific literature
      available on L. leonurus. METHODS: An extensive review of the literature from
      1900 to 2015 was carried out. Electronic databases including Scopus, SciFinder,
      Pubmed, Google Scholar and Google were used as data sources. All abstracts, full
      text articles and books written in English were considered. RESULTS: The
      phytochemistry of particularly the non-volatile constituents of L. leonurus has
      been comprehensively investigated due to interest generated as a result of the
      wide variety of biological effects reported for this plant. More than 50
      compounds have been isolated and characterised. L. leonurus contains mainly
      terpenoids, particularly labdane diterpenes, the major diterpene reported is
      marrubiin. Various other compounds have been reported by some authors to have
      been isolated from the plant, including, in the popular literature only, the
      mildly psychoactive alkaloid, leonurine. Leonurine has however, never been
      reported by any scientific analysis of the extracts of L. leonurus. CONCLUSION:
      Despite the publication of various papers on L. leonurus, there is still,
      however, the need for definitive research and clarification of other compounds,
      including alkaloids and essential oils from L. leonurus, as well as from other
      plant parts, such as the roots which are extensively used in traditional
      medicine. The traditional use by smoking also requires further investigation as
      to how the chemistry and activity are affected by this form of administration.
      Research has proven the psychoactive effects of the crude extract of L. leonurus,
      but confirmation of the presence of psychoactive compounds, as well as isolation
      and characterization, is still required. Deliberate adulteration of L. leonurus
      with synthetic cannabinoids has been reported recently, in an attempt to
      facilitate the marketing of these illegal substances, highlighting the necessity
      for refinement of appropriate quality control processes to ensure safety and
      quality. Much work is therefore still required on the aspect of quality control
      to ensure safety, quality and efficacy of the product supplied to patients, as
      this plant is widely used in South Africa as a traditional medicine. Commercially
      available plant sources provide a viable option for phytochemical research,
      particularly with regard to the appropriate validation of the plant material
      (taxonomy) in order to identify and delimit closely related species such as L.
      leonurus and L. nepetifolia which are very similar in habit.

PMID- 26292024
TI  - Genetic Analysis and Species Specific Amplification of the Artemisinin Resistance
      Associated Kelch Propeller Domain in P. falciparum and P. vivax.
AB  - Plasmodium falciparum resistance to artemisinin has emerged in the Greater Mekong
      Subregion and now poses a threat to malaria control and prevention. Recent work
      has identified mutations in the kelch propeller domain of the P. falciparum K13
      gene to be associated artemisinin resistance as defined by delayed parasite
      clearance and ex vivo ring stage survival assays. Species specific primers for
      the two most prevalent human malaria species, P. falciparum and P. vivax, were
      designed and tested on multiple parasite isolates including human, rodent, and
      non- humans primate Plasmodium species. The new protocol described here using the
      species specific primers only amplified their respective species, P. falciparum
      and P. vivax, and did not cross react with any of the other human malaria
      Plasmodium species. We provide an improved species specific PCR and sequencing
      protocol that could be effectively used in areas where both P. falciparum and P.
      vivax are circulating. To design this improved protocol, the kelch gene was
      analyzed and compared among different species of Plasmodium. The kelch propeller
      domain was found to be highly conserved across the mammalian Plasmodium species. 

PMID- 26292026
TI  - A Comparison of Three Different Thick Epinucleus Removal Techniques in Cataract
      Surgery.
AB  - PURPOSE: To compare the outcomes of cataract surgery performed with three
      different types of the epinucleus removal techniques (safe boat,
      infusion/aspiration (I/A) cannulas, and phacoemulsification tip). METHODS: Ninety
      eyes with thick adhesive epinuclei were randomly subdivided into three groups
      according to epinucleus removal technique: epinucleus floating (safe boat)
      technique, 30 patients; I/A tip, 30 patients; and phaco tip, 30 patients.
      Intraoperative measurements included ultrasound time (UST), mean cumulative
      dissipated ultrasound energy (CDE), and balanced salt solution (BSS) use.
      Clinical measurements were made preoperatively, and at one day, one month and two
      months postoperatively, including the best corrected visual acuity (BCVA), the
      central corneal thickness (CCT), and the endothelial cell count (ECC). RESULTS:
      Intraoperative measurements showed significantly less UST, CDE, and BSS use in
      the safe boat group than in the phaco tip groups (p < 0.05). The percentage of
      endothelial cell loss in the safe boat group was significantly lower than that in
      the phaco tip groups at two months post-cataract surgery (p < 0.05). CONCLUSIONS:
      The safe boat technique is a safer and more effective epinucleus removal
      technique than phaco tip techniques in cases with thick epinucleus.

PMID- 26292025
TI  - Low-dose arsenic-mediated metabolic shift is associated with activation of Polo
      like kinase 1 (Plk1).
AB  - Arsenic is a well-established human carcinogen associated with cancers of the
      skin, liver, lung, kidney, and bladder. Although numerous carcinogenic pathways
      have been proposed, the molecular mechanisms underlying arsenic-associated cancer
      etiology are still elusive. The cellular responses to arsenic exposure are dose
      dependent. It was recently shown that low-dose arsenic leads to a metabolic shift
      from mitochondrial respiration to aerobic glycolysis via inactivation of tumor
      suppressor p53 and activation of NF-kappaB. However, how inactivation of p53,
      activation of NF-kappaB, and metabolic change are coordinated in response to low
      dose arsenic exposure is still not completely understood. Polo-like kinase 1
      (Plk1) is a well- documented regulator in many cell cycle-related events. Herein,
      we showed that low-dose arsenic leads to elevation of Plk1 in an NF-kappaB
      dependent manner and that elevation of Plk1 contributes to the metabolic change
      from oxidative phosphorylation to glycolysis via activation of the PI3K/AKT/mTOR
      pathway. Furthermore, we showed that inhibition/depletion of Plk1 reverses low
      dose arsenic-associated phenotypes, including enhanced cell proliferation,
      activation of the PI3K/AKT/mTOR pathway, and increased glycolysis. Finally,
      inhibition of the PI3K/AKT/mTOR pathway also antagonizes the enhanced glycolytic
      influx due to low-dose arsenic exposure. Our studies support the notion that Plk1
      likely plays a critical role in cellular responses to low-dose arsenic. 

PMID- 26292029
TI  - Psycho-oncology assessment in Chinese populations: a systematic review of quality
      of life and psychosocial measures.
AB  - This systematic review describes psychosocial and quality of life (QOL) measures
      used in psycho-oncology research with cancer patients and caregivers in China.
      Medline and PsycINFO databases were searched (1980-2014). Studies reviewed met
      the following criteria: English language; peer-reviewed; sampled Chinese cancer
      patients/caregivers; developed, validated or assessed psychometric properties of
      psychosocial or QOL outcome measures; and reported validation data. The review
      examined characteristics of measures and participants, translation and cultural
      adaptation processes and psychometric properties of the measures. Ninety five
      studies met review criteria. Common characteristics of studies reviewed were
      they: assessed primarily QOL measures, sampled patients with breast, colorectal,
      or head and neck cancer, and validated existing measures (>80%) originating in
      North America or Europe. Few studies reported difficulties translating measures.
      Regarding psychometric properties of the measures >50% of studies reported
      subscale reliabilities <alpha = 0.70, <50% reported test-retest reliability, and
      <30% reported divergent validity. Few reported sensitivity, specificity or
      responsiveness. Improved accuracy and transparency of reporting for translation,
      cultural adaptation and psychometric testing of psychosocial measures is needed.
      Developing support structures for translating and validating psychosocial
      measures would enable this and ensure Chinese psycho-oncology clinical practice
      and research keeps pace with international focus on patient reported outcome
      measures and data management. 

PMID- 26292027
TI  - Controlled Human Malaria Infection (CHMI) differentially affects cell-mediated
      and antibody responses to CSP and AMA1 induced by adenovirus vaccines with and
      without DNA-priming.
AB  - We have previously shown that a DNA-prime followed by an adenovirus-5 boost
      vaccine containing CSP and AMA1 (DNA/Ad) successfully protected 4 of 15 subjects
      to controlled human malaria infection (CHMI). However, the adenovirus-5 vaccine
      alone (AdCA) failed to induce protection despite eliciting cellular responses
      that were often higher than those induced by DNA/Ad. Here we determined the
      effect of CHMI on pre-CHMI cellular and antibody responses against CSP and AMA1
      expressed as fold-changes in activities. Generally, in the DNA/Ad trial, CHMI
      caused pre-CHMI ELISpot IFN-gamma and CD8+ T cell IFN-gamma responses of the
      protected subjects to fall but among non-protected subjects, CHMI caused rises of
      pre-CHMI ELISpot IFN-gamma but falls of CD8+ T cell IFN-gamma responses. In
      contrast in the AdCA trial, CHMI caused both pre-CHMI ELISpot IFN-gamma and CD8+
      T cell IFN-gamma responses of the AdCA subjects to fall. We suggest that the
      falls in activities are due to migration of peripheral CD8+ T cells to the liver
      in response to developing liver stage parasites, and this fall, in the DNA/Ad
      trial, is masked in ELISpot responses of the non-protected subjects by rises in
      other immune cell types. In addition, CHMI caused falls in antibody activities of
      protected subjects, but rises in non-protected subjects in both trials to CSP,
      and dramatically in the AdCA trial to AMA1, reaching 380 MUg/ml that is probably
      due to boosting by transient blood stage infection before chloroquine treatment.
      Taken together, these results further define differences in cellular responses
      between DNA/Ad and AdCA trials, and suggest that natural transmission may boost
      responses induced by these malaria vaccines especially when protection is not
      achieved.

PMID- 26292028
TI  - Salmonella induces PD-L1 expression in B cells.
AB  - Salmonella persists for a long time in B cells; however, the mechanism(s) through
      which infected B cells avoid effector CD8 T cell responses has not been
      characterized. In this study, we show that Salmonella infects and survives within
      all B1 and B2 cell subpopulations. B cells are infected with a Salmonella
      typhimurium strain expressing an ovalbumin (OVA) peptide (SIINFEKL) to evaluate
      whether B cells process and present Salmonella antigens in the context of MHC-I
      molecules. Our data showed that OVA peptides are presented by MHC class I K(b)
      restricted molecules and the presented antigen is generated through proteasomal
      degradation and vacuolar processing. In addition, Salmonella-infected B cells
      express co-stimulatory molecules such as CD40, CD80, and CD86 as well as
      inhibitory molecules such as PD-L1. Thus, the cross-presentation of Salmonella
      antigens and the expression of activation molecules suggest that infected B cells
      are able to prime and activate specific CD8(+) T cells. However, the Salmonella
      infection-stimulated expression of PD-L1 suggests that the PD-1/PD-L1 pathway may
      be involved in turning off the cytotoxic effector response during Salmonella
      persistent infection, thereby allowing B cells to become a reservoir for the
      bacteria. 

PMID- 26292032
TI  - Retraction for Yang et al., Y4lO of Rhizobium sp. Strain NGR234 Is a Symbiotic
      Determinant Required for Symbiosome Differentiation.

PMID- 26292034
TI  - Analytic Intermodel Consistent Modeling of Volumetric Human Lung Dynamics.
AB  - Human lung undergoes breathing-induced deformation in the form of inhalation and
      exhalation. Modeling the dynamics is numerically complicated by the lack of
      information on lung elastic behavior and fluid-structure interactions between air
      and the tissue. A mathematical method is developed to integrate deformation
      results from a deformable image registration (DIR) and physics-based modeling
      approaches in order to represent consistent volumetric lung dynamics. The
      computational fluid dynamics (CFD) simulation assumes the lung is a poro-elastic
      medium with spatially distributed elastic property. Simulation is performed on a
      3D lung geometry reconstructed from four-dimensional computed tomography (4DCT)
      dataset of a human subject. The heterogeneous Young's modulus (YM) is estimated
      from a linear elastic deformation model with the same lung geometry and 4D lung
      DIR. The deformation obtained from the CFD is then coupled with the displacement
      obtained from the 4D lung DIR by means of the Tikhonov regularization (TR)
      algorithm. The numerical results include 4DCT registration, CFD, and optimal
      displacement data which collectively provide consistent estimate of the
      volumetric lung dynamics. The fusion method is validated by comparing the optimal
      displacement with the results obtained from the 4DCT registration. 

PMID- 26292030
TI  - Establishment of a yeast platform strain for production of p-coumaric acid
      through metabolic engineering of aromatic amino acid biosynthesis.
AB  - Aromatic amino acids are precursors of numerous plant secondary metabolites with
      diverse biological functions. Many of these secondary metabolites are already
      being used as active pharmaceutical or nutraceutical ingredients, and there are
      numerous exploratory studies of other compounds with promising applications. p
      Coumaric acid is derived from aromatic amino acids and, besides being a valuable
      chemical building block, it serves as precursor for biosynthesis of many
      secondary metabolites, such as polyphenols, flavonoids, and some polyketides.
      Here we developed a p-coumaric acid-overproducing Saccharomyces cerevisiae
      platform strain. First, we reduced by-product formation by knocking out
      phenylpyruvate decarboxylase ARO10 and pyruvate decarboxylase PDC5. Second,
      different versions of feedback-resistant DAHP synthase and chorismate mutase were
      overexpressed. Finally, we identified shikimate kinase as another important flux
      controlling step in the aromatic amino acid pathway by overexpressing enzymes
      from Escherichia coli, homologous to the pentafunctional enzyme Aro1p and to the
      bifunctional chorismate synthase-flavin reductase Aro2p. The highest titer of p
      coumaric acid of 1.93 +/- 0.26 g L(-1) was obtained, when overexpressing tyrosine
      ammonia-lyase TAL from Flavobacterium johnsoniaeu, DAHP synthase ARO4(K229L),
      chorismate mutase ARO7(G141S) and E. coli shikimate kinase II (aroL) in
      Deltapdc5Deltaaro10 strain background. To our knowledge this is the highest
      reported titer of an aromatic compound produced by yeast. The developed S.
      cerevisiae strain represents an attractive platform host for production of p
      coumaric-acid derived secondary metabolites, such as flavonoids, polyphenols, and
      polyketides.

PMID- 26292035
TI  - Prevalence of hemoglobin E in Yunnan Province of Southwest China.
AB  - OBJECTIVE: The aim of this study was to investigate the prevalence of hemoglobin
      E (Hb E) as well as the hematological and the phenotypic features of Hb E-related
      disorders in Yunnan Province of Southwest China. METHODS: A total of 30,908
      individuals from more than 30 nationalities who were childbearing population were
      recruited in the present study. Hematological analysis including complete blood
      counts and quantification of Hb levels were performed by capillary
      electrophoresis. The identified carriers were further detected for molecular
      analysis by multiple gap-polymerase chain reactions (gap-PCR) and the PCR-reverse
      dot-blot. RESULTS: Hematological results showed that 345 subjects were identified
      to be Hb E carriers (1.1%). The high incidence of carrying Hb E occurred in
      Achang (25.0%), Jingpo (23.5%), Dai (16.0%), and Lisu (13.6%). After performing
      molecular analysis in 201 carriers, 192 cases (95.5%) were heterozygous Hb E and
      29 cases (14.4%) of Hb E were con-inherited with alpha-thal cases. The other beta
      globin chain mutation included homozygous Hb E (three cases), beta(+)-thal/Hb E
      (one case) and beta(0)-thal/Hb E (five cases). Individuals in Dai had the most
      types of Hb E-related disorders. Severe anemia was observed in cases of beta(+)
      thal/Hb E and beta(0)-thal/Hb E. CONCLUSIONS: There is a high prevalence of Hb E
      among Yunnan populations, especially in ethnic groups. In addition, the spectrums
      of Hb gene mutations would provide a support for the genetic counseling of Hb E
      related disorders among Yunnan populations.

PMID- 26292036
TI  - Obesity Hypoventilation Syndrome: Weighing in on Therapy Options.
AB  - Obesity hypoventilation syndrome is becoming an increasingly encountered
      condition both in respiratory outpatient clinics and in hospitalized patients.
      The health consequences and social disadvantages of obesity hypoventilation
      syndrome are significant. Unfortunately, the diagnosis and institution of
      appropriate therapy is commonly delayed when the syndrome is not recognized or
      misdiagnosed. Positive airway pressure therapy remains the mainstay of treatment
      and is effective in controlling sleep-disordered breathing and improving awake
      blood gases in the majority of individuals. Evidence supporting one mode of
      therapy over another is limited. Both continuous and bilevel therapy modes can
      successfully improve daytime gas exchange, with adherence to therapy an important
      modifiable factor in the response to treatment. Despite adherence to therapy,
      these individuals continue to experience excess mortality primarily due to
      cardiovascular events compared with those with eucapnic sleep apnea using CPAP.
      This difference likely arises from ongoing systemic inflammation secondary to the
      morbidly obese state. The need for a comprehensive approach to managing
      nutrition, weight, and physical activity in addition to reversal of sleep
      disordered breathing is now widely recognized. Future studies need to evaluate
      the impact of a more aggressive and comprehensive treatment plan beyond managing
      sleep-disordered breathing. The impact of early identification and treatment of
      sleep-disordered breathing on the development and reversal of cardiometabolic
      dysfunction also requires further attention.

PMID- 26292037
TI  - Self-assembly of polydimethylsiloxane structures from 2D to 3D for bio-hybrid
      actuation.
AB  - This work aims to demonstrate the feasibility of a novel approach for the
      development of 3D self-assembled polydimethylsiloxane structures, to be used as
      engineered flexible matrices for bio-hybrid actuation. We described the
      fabrication of engineered bilayers, organized in a 3D architecture by means of a
      stress-induced rolling membrane technique. Such structures were provided with ad
      hoc surface topographies, for both cell alignment and cell survival after
      membrane rolling. We reported the results of advanced finite element model
      simulations, predicting the system behavior in terms of overall contraction,
      induced by the contractile activity of muscle cells seeded on the membrane. Then,
      we tested in vitro the structure with primary cardiomyocytes to evaluate the real
      bio-actuator contraction, thus validating the simulation results. At a later
      stage, we provided the samples with a stable fibronectin coating, by covalently
      binding the protein on the polymer surface, thus enabling long-term cultures with
      C2C12 skeletal muscle cells, a more controllable cell type. These tests revealed
      cell viability and alignment on the rolled structures, but also the ability of
      cells to differentiate and to form multinucleated and oriented myotubes on the
      polymer surface, also supported by a fibroblast feeder layer. Our results
      highlighted the possibility of developing 3D rolled PDMS structures,
      characterized by different mechanical properties, as novel bio-hybrid actuators. 

PMID- 26292038
TI  - Decreased Skeletal Muscle Mass is Associated with an Increased Risk of Mortality
      after Radical Nephrectomy for Localized Renal Cell Cancer.
AB  - PURPOSE: We evaluate the association between severe skeletal muscle deficiency or
      sarcopenia, and disease progression, cancer specific mortality and all cause
      mortality in patients with localized renal cell carcinoma treated with radical
      nephrectomy. MATERIALS AND METHODS: The baseline lumbar skeletal muscle index of
      387 patients treated with radical nephrectomy for nonmetastatic renal cell
      carcinoma between 2000 and 2010 was measured on preoperative computerized
      tomography. Sarcopenia was classified according to gender specific consensus
      definitions as male-skeletal muscle index less than 55 cm(2)/m(2) and female
      skeletal muscle index less than 39 cm(2)/m(2). Progression-free, cancer specific
      and overall survival was estimated with the Kaplan-Meier method. Associations
      with progression, cancer specific mortality and all cause mortality were
      summarized with hazard ratios. RESULTS: Of 387 patients 180 (47%) had sarcopenia.
      Patients with sarcopenia were older, more likely to be male (77% vs 56%, p
      <0.001), to have a smoking history (67% vs 55%, p=0.02), and to have nuclear
      grade 3 or greater disease (67% vs 60%, p=0.05), but were otherwise similar to
      patients without sarcopenia. Median postoperative followup was 7.2 years.
      Patients with sarcopenia had inferior 5-year cancer specific survival (79% vs
      85%, p=0.05) compared to those without sarcopenia, as well as significantly worse
      5-year overall survival (65% vs 74%, p= 0.005). As a continuous variable,
      increasing skeletal muscle index was linearly associated with a decreased risk of
      cancer specific mortality and all cause mortality. Moreover, on multivariable
      analysis sarcopenia was associated with increased cancer specific mortality (HR
      1.70, p=0.047) and all cause mortality (HR 1.48, p=0.039). CONCLUSIONS:
      Sarcopenia is independently associated with cancer specific mortality and all
      cause mortality after radical nephrectomy for renal cell carcinoma. These
      findings underscore the importance of assessing skeletal muscle index for risk
      stratification, patient counseling and treatment planning.

PMID- 26292039
TI  - Preoperative Testing for Urethral Sling Surgery for Stress Urinary Incontinence:
      Overuse, Underuse and Cost Implications.
AB  - PURPOSE: We identify areas of overuse and underuse in the preoperative evaluation
      of patients undergoing mid urethral sling surgery. We also estimate the effect of
      overuse of preoperative testing on health care costs. MATERIALS AND METHODS: We
      conducted a retrospective review of women who underwent sling surgery with or
      without concomitant prolapse repair between 2012 and 2013. Physician orders for
      preoperative electrocardiogram, chest x-ray, basic metabolic panel, complete
      blood count, coagulation studies and urinalysis were classified as appropriate or
      inappropriate based on summary guidelines from the American Academy of Family
      Physicians. The additional costs of inappropriate tests were estimated using the
      2014 Medicare clinical laboratory and physician fee schedules. RESULTS: A total
      of 101 women who underwent mid urethral sling surgery were identified and 346
      preoperative tests were ordered. Overall 76% of coagulation profiles, 73% of
      complete blood counts, 47% of basic metabolic panels, 39% of chest x-rays and 21%
      of electrocardiograms ordered did not have an appropriate clinical indication. In
      addition, 6% of electrocardiograms, 22% of chest x-rays and 10% of urinalyses
      were not ordered despite an appropriate indication. The estimated charges of
      overused tests were $1,844.15 for the cohort, or $18 per patient. CONCLUSIONS:
      Preoperative testing is overused as well as underused in patients undergoing
      sling surgery. The greatest variation occurred with the use of
      electrocardiograms, chest x-rays and urinalysis. Poor adherence to national
      guidelines leads to increased health care costs and warrants increased awareness
      in following evidence-based guidelines.

PMID- 26292040
TI  - Improved 5-Factor Prognostic Classification of Patients Receiving Salvage
      Systemic Therapy for Advanced Urothelial Carcinoma.
AB  - PURPOSE: Prognostic factors in patients receiving salvage systemic therapy for
      advanced urothelial carcinoma include performance status, liver metastasis,
      hemoglobin and time since chemotherapy. We investigated the impact of albumin,
      and neutrophil, lymphocyte and platelet counts. MATERIALS AND METHODS: Patient
      level data from 10 phase II trials were used. Cox proportional hazards regression
      was applied to evaluate associations with overall survival. An optimal regression
      model was constructed using forward stepwise selection and risk groups were
      defined using the number of adverse factors. Trial was a stratification factor.
      External validation was done in a separate data set of 5 salvage phase II trials.
      RESULTS: Discovery data were obtained on 708 patients. After adjustment for the 4
      known factors a platelet count of the upper limit of normal or greater and
      albumin less than the lower limit of normal were significant poor prognostic
      factors. Only the addition of albumin was externally validated. For 0 or 1, 2 and
      3 or greater risk factors median overall survival was 8.9, 6.4 and 4.5 months in
      207, 171 and 113 patients in the discovery data set of 491, and 10.6, 10.0 and
      7.0 months in 73, 47 and 47 patients, respectively, in the validation data set of
      167. By adding albumin the c-index improved from 0.610 to 0.639 in the discovery
      set and from 0.616 to 0.646 in the validation set. CONCLUSIONS: Albumin was
      externally validated as a prognostic factor for overall survival after accounting
      for time from prior chemotherapy, hemoglobin, performance status and liver
      metastasis status in patients receiving salvage systemic therapy for advanced
      urothelial carcinoma. The discovery of molecular prognostic factors is a priority
      to further enhance this new preferred 5-factor clinical prognostic model.

PMID- 26292041
TI  - The Presence of Oxalobacter formigenes in the Microbiome of Healthy Young Adults.
AB  - PURPOSE: Oxalobacter formigenes, a member of the human colonic microbiota with a
      major role in net colonic oxalate transport and secretion, is protective against
      the formation of calcium oxalate kidney stones. We describe the prevalence,
      relative abundance and stability of O. formigenes in healthy young adults in the
      United States. MATERIALS AND METHODS: We used HMP (Human Microbiome Project) data
      on fecal samples from 242 healthy young adults who had 1 to 3 study visits.
      Samples underwent whole genomic shotgun sequencing and/or 16S rRNA sequencing.
      Three data sets available from the processed sequence data were studied,
      including whole genomic shotgun metagenomic analysis by alignment to reference
      genomes using shotgun community profiling, or MetaPhlAn
      (http://huttenhower.sph.harvard.edu/metaphlan) or QIIME (http://qiime.org/)
      analysis of the V1-3 or V3-5 16S sequences. RESULTS: O. formigenes was detected
      in fecal samples using whole genomic shotgun and 16S rRNA data. Analysis of the
      whole genomic shotgun data set using shotgun community profiling showed that 29
      of 94 subjects (31%) were O. formigenes positive. V1-3 and V3-5 analyses were
      less sensitive for O. formigenes detection. When present, O. formigenes relative
      abundance varied over 3 log10 and was normally distributed. All assays agreed in
      58 of 66 samples (88%) studied by all 3 methods. Of 14 subjects who were O.
      formigenes positive at baseline 13 (93%) were positive at the followup visit,
      indicating the stability of colonization. CONCLUSIONS: O. formigenes appears to
      be stably present in fewer than half of healthy young adults in the United
      States. It is most sensitively detected by whole genomic shotgun.

PMID- 26292042
TI  - Prognostic Significance of Sarcopenia in Patients with Metastatic Renal Cell
      Carcinoma.
AB  - PURPOSE: Sarcopenia, a novel concept reflecting the degenerative loss of skeletal
      muscle mass, is a critical physiological change during the development of cancer
      cachexia. We retrospectively investigated the prognostic role of sarcopenia in
      patients with metastatic renal cell carcinoma. MATERIALS AND METHODS: Skeletal
      muscle index was calculated using computerized tomography performed at the
      diagnosis of metastatic renal cell carcinoma. Sarcopenia was defined as skeletal
      muscle index less than 43 cm(2)/m(2) for males with a body mass index less than
      25 kg/m(2), less than 53 cm(2)/m(2) for males with a body mass index 25 kg/m(2)
      or greater, and less than 41 cm(2)/m(2) for females. The relationship between
      sarcopenia and overall survival was assessed in 92 patients with metastatic renal
      cell carcinoma using Cox proportional hazards models. The predictive accuracy of
      these models was evaluated using the c-index. RESULTS: A total of 63 (68%)
      patients were classified as having sarcopenia and 52 (57%) died (median overall
      survival 27 months) during followup (median 19 months). A multivariate analysis
      identified sarcopenia as a significant and independent predictor of overall
      survival (HR 2.58, p = 0.015), along with prior nephrectomy (p <0.001), number of
      metastatic sites (p = 0.017), corrected calcium (p = 0.026) and lactate
      dehydrogenase (p = 0.006). The 3-year overall survival rates were 31% and 73% for
      sarcopenic and nonsarcopenic cases, respectively (p <0.001). The integration of
      sarcopenia into the Memorial Sloan Kettering Cancer Center risk model improved
      the c-index from 0.726 to 0.758 (addition of sarcopenia to the original model)
      and 0.755 (substitution of sarcopenia for Karnofsky performance status).
      CONCLUSIONS: Sarcopenia is a significant prognostic factor in metastatic renal
      cell carcinoma.

PMID- 26292044
TI  - Fetal presentation and successful twin vaginal delivery.
AB  - BACKGROUND: Despite the demonstrated safety of a trial of labor for pregnancies
      with a vertex-presenting twin and clinical guidelines in support of this plan,
      the rate of planned cesarean delivery for twin pregnancies remains high. This
      high rate, as well as variation in cesarean rates for twin pregnancies across
      providers, may be influenced strongly by concern about delivery of the second
      twin, particularly when it is in a nonvertex presentation. There are limited data
      in the literature that has examined the impact of the position of the
      nonpresenting twin on successful vaginal delivery or maternal/neonatal morbidity.
      OBJECTIVE: We hypothesized that nonvertex presentation of the second twin would
      be associated with lower rates of successful vaginal birth for those patients
      attempting labor. STUDY DESIGN: This institutional review board-approved,
      retrospective cohort study of women who labored with twin pregnancies in a single
      urban hospital from 2007-2011. We included women with vertex-presenting first
      twins at >32 weeks gestation without a contraindication to labor and excluded
      those with uterine scar or lethal fetal anomaly. Vaginal delivery rates were
      evaluated according to vertex or nonvertex presentation of the second twin at
      admission and again at delivery. Maternal and neonatal morbidities were evaluated
      separately. Logistic regression was used to control for multiple confounders.
      RESULTS: Seven hundred sixteen patients met the inclusion criteria; 349 patients
      (49%) underwent a trial of labor. This included 73% (296/406) of eligible
      vertex/vertex twins and 17% (53/310) eligible vertex/nonvertex twins (P < .01).
      When compared with laboring patients with vertex/vertex-presenting twins, those
      with vertex/nonvertex twins were younger (median age, 32 vs 33 years; P = .05),
      were more often multiparous (60% vs 43%; P = .02), and were less likely to have
      hypertension (13% vs 27%; P = .03). Eighty-five percent of patients with
      nonvertex second twins at admission delivered vaginally, compared with 70% of
      patients with vertex second twins (P = .02). After we controlled for confounders,
      the difference was not statistically significant (adjusted odds ratio, 2.10; 95%
      confidence interval, 0.93-4.73). In the subset of patients with nonvertex second
      twins at delivery, those who initiated labor had an 89% vaginal delivery rate,
      compared with a 56% rate for those who changed from vertex to nonvertex
      presentation during labor (adjusted odds ratio, 19.90; 95% confidence interval,
      3.86-102.78). Labor induction and increasing provider years in practice were also
      significant positive predictors of vaginal birth when the second twin was
      nonvertex at delivery. Maternal and neonatal morbidity was low and similar
      between groups, although 8% of women with nonvertex second twins experienced
      cervical lacerations, compared with 1% with vertex second twins (P = .01).
      CONCLUSION: Patients with nonvertex second twins had comparable, if not higher,
      rates of vaginal delivery than their vertex-presenting counterparts. The higher
      rate of vaginal delivery with stable nonvertex lie and the association with labor
      induction and the physician's years in practice all suggest a role for provider
      selection and delivery planning. These findings and the observed 11% rate of
      intrapartum presentation change support vaginal delivery of the nonvertex second
      twin.

PMID- 26292043
TI  - The Who, How and What of Real-World Penile Implantation in 2015: The PROPPER
      Registry Baseline Data.
AB  - PURPOSE: To date, the published data on patients treated with penile implantation
      generally consist of small series of single surgeon, retrospective experiences
      rather than prospective or large, multicenter evaluations. This study establishes
      a baseline of data collection from the PROPPER (Prospective Registry of Outcomes
      with Penile Prosthesis for Erectile Restoration). The PROPPER is the first large,
      prospective, multicenter, multinational, monitored, and internal review board
      approved study of real-world outcomes for patients with penile implants.
      MATERIALS AND METHODS: Data from the PROPPER study were examined to determine
      patient baseline characteristics and primary and secondary etiologies before
      treatment of erectile dysfunction. Data include type and size of implant
      received, surgical steps/techniques used during implantation, and duration of
      hospital stay. RESULTS: Through April 2, 2015 a total of 1,019 patients were
      enrolled in the study at 11 sites, with radical prostatectomy being the
      predominant etiology in 285 (28%). Of those 285 patients treated with radical
      prostatectomy 280 (98.2%) received an AMS 700TM. Of these patients 65.0% (182 of
      280) had placement of the reservoir in the traditional retropubic space vs 31.8%
      (89 of 280) in a submuscular location. Of those patients not treated with radical
      prostatectomy receiving an AMS 700, fewer underwent reservoir placement in the
      submuscular location (17.7%, 124 of 702, vs 80.9%, 568 of 702; p <0.001). Of
      those patients receiving an AMS 700, those treated with radical prostatectomy and
      those with diabetes had more outpatient admissions (less than 24 hours, 56.8% and
      52.1%, respectively) compared to those with cardiovascular disease and Peyronie's
      disease (42.0% and 35.6%, respectively, p <0.001). CONCLUSIONS: This first-of-its
      kind, large, prospective, multicenter study reveals most penile implant cases in
      North America receive an inflatable penile prosthesis and that radical
      prostatectomy is the most common primary etiology of penile implant surgery.
      Moreover, patients treated with radical prostatectomy were more likely to have
      the reservoir placed in a submuscular location, have a longer operating room time
      and be admitted to the hospital overnight compared with other patient groups.

PMID- 26292045
TI  - Indomethacin as a tocolytic harmful to preterm infant.

PMID- 26292046
TI  - Hospital variation in cesarean delivery rates: contribution of individual and
      hospital factors in Florida.
AB  - BACKGROUND: Primary cesarean deliveries are a major contributor to the large
      increase in cesarean delivery rates in the United States over the past 2 decades
      and are an essential focus for the reduction of related morbidity and costs.
      Studies have shown that primary cesarean delivery rates among low-risk women in
      the United States vary 3-fold across hospitals and are not explained by
      differences in patient case-mix. However, the extent to which maternal vs
      hospital characteristics contribute to this variation remains poorly understood
      because previous studies were limited in scope and did not assess the influence
      of factors such as maternal ethnicity subgroups or prepregnancy obesity.
      OBJECTIVE: We assessed the contribution of individual- and hospital-level risk
      factors to the hospital variation in primary cesarean delivery rates among low
      risk women in Florida. STUDY DESIGN: Our population-based retrospective cohort
      study used Florida's linked birth certificate and hospital discharge records for
      the period of 2004-2011. The study population was comprised of 412,192
      nulliparous, singleton, vertex, live births with labor at 37-40 weeks gestation
      in 122 nonmilitary delivery hospitals. Data were analyzed with logistic mixed
      effects regression with cesarean delivery as the outcome. This approach provided
      adjusted risk estimates at an individual and hospital level and the estimated
      percent of hospital variation statewide that was explained by these factors.
      RESULTS: The primary cesarean delivery rate in the study population was 23.9%,
      with hospital-specific estimates that ranged from 12.8-47.3%. Leading risk
      factors for cesarean delivery were maternal age >=35 years (adjusted relative
      risk, 2.22), prepregnancy obesity (body mass index, >=30 kg/m(2); adjusted
      relative risk, 1.73), medical risk conditions (adjusted relative risk, 1.72),
      labor induction (adjusted relative risk, 1.52), and delivery in hospitals located
      in Miami-Dade County (adjusted relative risk, 1.73). Hospital geographic location
      was a significant effect modifier for prepregnancy obesity, medical conditions,
      and labor induction (P < .05), with a tendency towards lower adjusted relative
      risks for these factors in Miami-Dade County relative to other Florida regions.
      Conversely, Miami-Dade County had an increased prevalence of higher-risk ethnic
      subgroups, such as Cuban or Puerto Rican mothers, and also substantially higher
      adjusted relative risks that were associated with practice-related factors, such
      as delivery during weekday hours. Whereas hospital geographic location
      contributed to 39.6% of the observed variation statewide, the estimated
      contribution of maternal ethnicity ranged from 1.6-15.7% among Florida regions.
      CONCLUSIONS: Hospital geographic location contributes to hospital variation in
      primary cesarean delivery rates among low-risk women in Florida. In contrast to
      previous studies, our findings suggest that individual level risk factors such as
      maternal ethnicity also contribute to some of this variation, with differing
      extent by region. These individual factors likely interact with practice factors
      and add to the variation. This study was limited by not including maternal Bishop
      score before induction or obstetrics provider in the analysis. These were not
      available on the dataset but likely contribute to the variation. Our findings
      suggest potential issues to consider in quality improvement efforts, such as the
      need for future qualitative research that focuses on mothers in higher-risk
      ethnic subgroups and providers in high-rate hospitals, particularly those in
      Miami-Dade County. These studies may help to identify potential cultural
      differences in maternal beliefs and expectations for delivery and maternal
      reasons for differences in obstetrics practices.

PMID- 26292047
TI  - Reply: To PMID 25577672.

PMID- 26292048
TI  - #37: Diagnosis and management of vasa previa.
AB  - Vasa previa occurs when fetal blood vessels that are unprotected by the umbilical
      cord or placenta run through the amniotic membranes and traverse the cervix. If
      membranes rupture, these vessels may rupture, with resultant fetal hemorrhage,
      exsanguination, or even death. Prenatal diagnosis of vasa previa by ultrasound
      scans is approximately 98%. Approximately 28% of prenatally diagnosed cases
      result in emergent preterm delivery. Management of prenatally diagnosed vasa
      previa includes antenatal corticosteroids between 28-32 weeks of gestation,
      considerations for preterm hospitalization at 30-34 weeks of gestation, and
      scheduled delivery at 34-37 weeks of gestation. 

PMID- 26292049
TI  - A cautionary note about Monsel's solution.

PMID- 26292050
TI  - Prenatal aneuploidy screening using cell-free DNA.

PMID- 26292051
TI  - A computational study of the effect of the metal organic framework environment on
      the release of chemically stored nitric oxide.
AB  - The use of copper based metal organic frameworks as a vehicle for the storage and
      delivery of chemically stored nitric oxide has been proposed based on recent
      experiments [J. Am. Chem. Soc., 2012, 134, 3330-3333]. In these experiments
      copper based metal organic frameworks (MOFs) suspended in ethanol catalytically
      convert chemically stored nitric oxide (in the S-nitrosothiol or RSNO form) to
      free nitric oxide at a slow and sustained rate, as compared to a quick release in
      a solution of ethanol containing free copper ions. In order to gain insight on
      the effect of the MOF environment on the catalytic activity, a combination of
      electronic structure calculations on representative clusters and classical
      simulations using a force-field (partly parameterized on the above calculations)
      is used to study a simple RSNO species, S-nitrosomethane (CH3SNO) as well as the
      biologically compatible S-nitrosocysteine, both in the MOF and free copper
      solution. The free energy profiles of bringing the RSNO species to the catalytic
      centers have been compared and related to the different solvation environments of
      the copper catalyst in the complex solvated MOF and in free copper solution.
      Surprisingly, in the case of the simple CH3SNO moiety as well as the S
      nitrosocysteine case, the free energy profile of bringing the first RSNO from the
      center of one of the pores to the catalytic site in the pore is very similar to
      the free solution case. On the other hand, bringing a second RSNO molecule to the
      same catalytic site or to the adjacent catalytic copper site show relatively
      higher barriers. These studies help shed light on the sustained nitric oxide
      release in the MOF environment. 

PMID- 26292052
TI  - Expression profiles of inka2 in the murine nervous system.
AB  - Dynamic rearrangement of the actin cytoskeleton impacts many cellular
      characteristics in both the developing and adult central nervous systems (CNS),
      including the migration and adhesion of highly motile neural progenitor cells,
      axon guidance of immature neurons, and reconstruction of synaptic structures in
      the adult brain. Inka1, a known regulator of actin cytoskeleton reconstruction,
      is predominantly expressed by the neural crest cell lineage and regulates the
      migration and differentiation of these cells. In the present study, we identified
      a novel gene, designated as inka2, which is related to inka1. Inka2/fam212b is an
      evolutionarily conserved gene found in different vertebrate species and
      constitutes a novel gene family together with inka1. Northern blot analysis
      showed that inka2 mRNA was highly enriched in the nervous system. The
      spatiotemporal propagation cell profiles of those cells that expressed inka2
      transcripts were compatible with those of Olig2-positive oligodendrocyte
      progenitor cells, which originate in the ventral ventricular zone during
      embryogenesis. Intense expression of inka2 was also noted in the proliferative
      neuronal progenitors in the developing cerebellum. On the other hand, immature
      newborn neurons in the embryonic brain showed no expression of inka2, except for
      the cells residing in the marginal zone of the embryonic telencephalon, which is
      known to contain transient cells including the non-subplate pioneer neurons and
      Cajal-Retzius cells. As brain development proceeds during the postnatal stage,
      inka2 expression emerged in some populations of immature neurons, including the
      neocortical pyramidal neurons, hippocampal pyramidal neurons, and granule cells
      migrating in the cerebellar cortex. In the adult brain, the expression of inka2
      was interestingly confined in terminally differentiated neurons in the restricted
      forebrain regions. Taken together, as a novel regulator of actin cytoskeletons in
      the CNS, inka2 may be involved in multiple actin-driven processes, including cell
      migration and establishment of neuronal polarity. 

PMID- 26292053
TI  - Fucoxanthin increases lifespan of Drosophila melanogaster and Caenorhabditis
      elegans.
AB  - The pharmacological activation of stress-defense mechanisms is one of the
      perspective ways to increase human lifespan. The goal of the present study was to
      study the effects on lifespan of Drosophila melanogaster and Caenorhabditis
      elegans of two carotenoids: beta-carotene and fucoxanthin, which are bioactive
      natural substances in human diet. In addition, the effects of carotenoids on the
      flies survival were studied under stress conditions, including starvation,
      thermal stress (35 degrees C), oxidative stress (20 mM paraquat), as well as
      locomotor activity, fecundity, and genes expression level. Our results
      demonstrated lifespan extension of flies by both carotenoids. However, the
      positive effects on the lifespan of C. elegans were revealed only for
      fucoxanthin. In presence of carotenoids decreased flies' fecundity, increased
      spontaneous locomotor activity and resistance to oxidative stress were detected.

PMID- 26292054
TI  - Combined abiotic and biotic in-situ reduction of hexavalent chromium in
      groundwater using nZVI and whey: A remedial pilot test.
AB  - The paper describes a pilot remediation test combining two Cr(VI) geofixation
      methods - chemical reduction by nanoscale zero-valent iron (nZVI) and subsequent
      biotic reduction supported by whey. Combination of the methods exploited the
      advantages of both - a rapid decrease in Cr(VI) concentrations by nZVI, which
      prevented further spreading of the contamination and facilitated subsequent use
      of the cheaper biological method. Successive application of whey as an organic
      substrate to promote biotic reduction of Cr(VI) after application of nZVI
      resulted in a further and long-term decrease in the Cr(VI) contents in the
      groundwater. The effect of biotic reduction was observed even in a monitoring
      well located at a distance of 22 m from the substrate injection wells after 10
      months. The results indicated a reciprocal effect of both the phases - nZVI
      oxidized to Fe(III) during the abiotic phase was microbially reduced back to
      Fe(II) and acted as a reducing agent for Cr(VI) even when the microbial density
      was already low due to the consumed substrate. Community analysis with
      pyrosequencing of the 16S rRNA genes further confirmed partial recycling of nZVI
      in the form of Fe(II), where the results showed that the Cr(VI) reducing process
      was mediated mainly by iron-reducing and sulfate-reducing bacteria.

PMID- 26292055
TI  - Immobilization of arsenate in kaolinite by the addition of magnesium oxide: An
      experimental and modeling investigation.
AB  - MgO was chosen as an As(V) immobilization agent and a series of immobilization
      experiments was performed to obtain insights into the behavior of As(V) and MgO
      during leaching tests. Our experimental and modeling results demonstrated that
      As(V) immobilization by MgO consists of the following steps: (i) an increase in
      sample pH, (ii) desorption of As(V) from the samples, and (iii) the re
      immobilization of As(V) by MgO/Mg(OH)2 particles. Regarding the behavior of MgO,
      the modeling results showed that when the MgO dosage was 25 mgMgO/4 g-drysample
      or less, the majority of MgO was used to increase pH, and less than 1% of MgO was
      used to sorb As(V), which was consistent with the result of leaching tests
      showing that a high level of As(V) was leached at the MgO dosages. On the other
      hand, when the MgO dosage was above 25 mgMgO/4 g-drysample, the percentage of MgO
      used for As(V) sorption increased up to 35%, and correspondingly, the As(V)
      leaching level decreased to below 0.01 mgAs/L at an MgO dosage of 75 mgMgO/4 g
      drysample. Additionally, when the MgO dosage was 50 mgMgO/4 g-drysample or more,
      it was found that more than 40% of MgO remained as fresh MgO without undergoing
      chemical reactions.

PMID- 26292056
TI  - Volatile trace compounds released from municipal solid waste at the transfer
      stage: Evaluation of environmental impacts and odour pollution.
AB  - Odour pollution caused by municipal solid waste is a public concern. This study
      quantitatively evaluated the concentration, environmental impacts, and olfaction
      of volatile trace compounds released from a waste transfer station. Seventy-six
      compounds were detected, and ethanol presented the highest releasing rate and
      ratio of 14.76 kg/d and 12.30 g/t of waste, respectively. Life cycle assessment
      showed that trichlorofluoromethane and dichlorodifluoromethane accounted for more
      than 99% of impact potentials to global warming and approximately 70% to human
      toxicity (non-carcinogenic). The major contributor for both photochemical ozone
      formation and ecotoxicity was ethanol. A detection threshold method was also used
      to evaluate odour pollution. Five compounds including methane thiol, hydrogen
      sulphide, ethanol, dimethyl disulphide, and dimethyl sulphide, with dilution
      multiples above one, were considered the critical compounds. Methane thiol showed
      the highest contribution to odour pollution of more than 90%, as indicated by its
      low threshold. Comparison of the contributions of the compounds to different
      environmental aspects indicated that typical pollutants varied based on specific
      evaluation targets and therefore should be comprehensively considered. This study
      provides important information and scientific methodology to elucidate the
      impacts of odourant compounds to the environment and odour pollution.

PMID- 26292057
TI  - Thermal stability and mechanism of decomposition of emulsion explosives in the
      presence of pyrite.
AB  - The reaction of emulsion explosives (ammonium nitrate) with pyrite was studied
      using techniques of TG-DTG-DTA. TG-DSC-MS was also used to analyze samples
      thermal decomposition process. When a mixture of pyrite and emulsion explosives
      was heated at a constant heating rate of 10K/min from room temperature to 350
      degrees C, exothermic reactions occurred at about 200 degrees C. The essence of
      reaction between emulsion explosives and pyrite is the reaction between ammonium
      nitrate and pyrite. Emulsion explosives have excellent thermal stability but it
      does not mean it showed the same excellent thermal stability when pyrite was
      added. Package emulsion explosives were more suitable to use in pyrite shale than
      bulk emulsion explosives. The exothermic reaction was considered to take place
      between ammonium nitrate and pyrite where NO, NO2, NH3, SO2 and N2O gases were
      produced. Based on the analysis of the gaseous, a new overall reaction was
      proposed, which was thermodynamically favorable. The results have significant
      implication in the understanding of stability of emulsion explosives in reactive
      mining grounds containing pyrite minerals. 

PMID- 26292058
TI  - Nanosuspensions as delivery system for gambogenic acid: characterization and in
      vitro/in vivo evaluation.
AB  - Nanosuspensions (NS) can enhance the saturation solubility and dissolution
      velocity of poorly soluble drugs. PEG as a non-ionic surfactant plays an
      important role in surface modification of nanoparticles for prolonging in vivo
      circulation. In this study, anti-solvent precipitation method was introduced to
      prepare gambogenic acid nanosuspensions (GNA-NS) with PVPK30 and PEG2000 as
      stabilizers to settle the disadvantages of GNA. The obtained nanoparticles were
      spherical with a mean particle size of 183.7 nm and a zeta potential of -22.8 mV.
      The entrapment efficiency and drug loading of the resultant formulation were 97.3
      and 29.73%. X-ray diffraction analysis confirmed the amorphous phase of GNA in
      NS. Fourier transform infrared indicated there may be hydrogen bond interaction
      between the drug and excipients. After lyophilization of GNA-NS, the freeze-dried
      powder displayed sufficient long-term physical stability at 4 and 25  degrees C.
      In comparison to GNA solution, in vitro studies of GNA-NS showed much slower
      release and higher cytotoxicity in HepG2 cells. What's more, the pharmacokinetic
      study in rats revealed that the AUC0-infinity and t1/2 of GNA-NS were increased
      2.63- and 1.77-fold than that of the reference formulation. Taken together, in
      vitro/in vivo evaluations showed NS would be an effectively strategy to change
      the poor aqueous solubility and prolong the half-life for GNA. The GNA-NS with
      enhanced bioavailability and drug efficacy provided a promising delivery system
      for the application of GNA.

PMID- 26292059
TI  - Waxy Laryngeal Mass.

PMID- 26292060
TI  - Human exposure to endocrine disrupting chemicals and fertility: A case-control
      study in male subfertility patients.
AB  - BACKGROUND: Dioxins, PCBs, chlorinated pesticides, brominated flame retardants,
      bisphenol A, triclosan, perfluorinated compounds and phthalates are known as
      endocrine disrupting chemicals (EDCs). OBJECTIVES: The aim of our study was to
      investigate whether higher exposure to EDCs is associated with increased
      subfertility in men. METHODS: We measured biomarkers of exposure in 163 men,
      recruited through four fertility clinics. According to WHO guidelines, we used a
      total motility count (TMC) of 20 million as cut-off value. We assigned patients
      to the case group when two semen samples - collected at least one week apart -
      had a TMC<20 and to the control group when both samples had a TMC>=20. To
      estimate the risk of subfertility and alteration in sex hormone concentrations we
      used multivariable-adjusted analysis, using logistic and linear regressions,
      respectively. RESULTS: For an IQR increase in serum oxychlordane, the odds ratio
      for subfertility was 1.98 (95% CI: 1.07; 3.69). Furthermore, men with serum
      levels of BDE209 above the quantification limit had an odds of 7.22 (1.03; 50.6)
      for subfertility compared with those having values below the LOQ. Urinary levels
      of phthalates and triclosan were negatively associated with inhibin B and
      positively with LH. Urinary bisphenol A correlated negatively with testosterone
      levels. CONCLUSIONS: Our study in men showed that internal body concentrations of
      endocrine disrupting chemicals are associated with an increased risk of
      subfertility together with alterations in hormone levels. The results emphasize
      the importance to reduce chemicals in the environment in order to safeguard male
      fertility.

PMID- 26292061
TI  - Using Social Network Analysis to Assess Mentorship and Collaboration in a Public
      Health Network.
AB  - INTRODUCTION: Addressing chronic disease burden requires the creation of
      collaborative networks to promote systemic changes and engage stakeholders.
      Although many such networks exist, they are rarely assessed with tools that
      account for their complexity. This study examined the structure of mentorship and
      collaboration relationships among members of the Healthy Aging Research Network
      (HAN) using social network analysis (SNA). METHODS: We invited 97 HAN members and
      partners to complete an online social network survey that included closed-ended
      questions about HAN-specific mentorship and collaboration during the previous 12
      months. Collaboration was measured by examining the activity of the network on 6
      types of products: published articles, in-progress manuscripts, grant
      applications, tools, research projects, and presentations. We computed network
      level measures such as density, number of components, and centralization to
      assess the cohesiveness of the network. RESULTS: Sixty-three respondents
      completed the survey (response rate, 65%). Responses, which included information
      about collaboration with nonrespondents, suggested that 74% of HAN members were
      connected through mentorship ties and that all 97 members were connected through
      at least one form of collaboration. Mentorship and collaboration ties were
      present both within and across boundaries of HAN member organizations.
      CONCLUSION: SNA of public health collaborative networks provides understanding
      about the structure of relationships that are formed as a result of participation
      in network activities. This approach may offer members and funders a way to
      assess the impact of such networks that goes beyond simply measuring products and
      participation at the individual level.

PMID- 26292062
TI  - Perceptions of the US National Tobacco Quitline Among Adolescents and Adults: A
      Qualitative Study, 2012-2013.
AB  - INTRODUCTION: Tobacco quitlines are critical components of comprehensive tobacco
      control programs. However, use of the US National Tobacco Quitline (1-800-QUIT
      NOW) is low. Promoting quitlines on cigarette warning labels may increase call
      volume and smoking cessation rates but only if smokers are aware of, and
      receptive to, quitline services. METHODS: We conducted qualitative interviews
      with a diverse subset (n = 159) of adolescent (14-17 y) and adult (>=18 y)
      participants of a larger quantitative survey about graphic cigarette warning
      labels (N = 1,590). A convenience sample was recruited from schools and community
      organizations in 6 states. Interviews lasted 30 to 45 minutes and included
      questions to assess basic knowledge and perceptions of the quitline number
      printed on the warning labels. Data were analyzed using content analysis.
      RESULTS: Four themes were identified: available services, caller characteristics,
      quitline service provider characteristics, and logistics. Participants were
      generally knowledgeable about quitline services, including the provision of
      telephone-based counseling. However, some adolescents believed that quitlines
      provide referrals to "rehab." Quitline callers are perceived as highly motivated 
      even desperate - to quit. Few smokers were interested in calling the quitline,
      but some indicated that they might call if they were unable to quit
      independently. It was generally recognized that quitline services are or should
      be free, confidential, and operated by governmental or nonprofit agencies,
      possibly using tobacco settlement funds. CONCLUSION: Future marketing efforts
      should raise awareness of the nature and benefits of quitline services to
      increase use of these services and, consequently, reduce tobacco use, improve
      public health, and reduce tobacco-related health disparities.

PMID- 26292064
TI  - Body Mass Index and Poor Self-Rated Health in 49 Low-Income and Middle-Income
      Countries, By Sex, 2002-2004.
AB  - This study investigated whether the relationship between body mass index (BMI)
      and poor self-rated health differed by sex in low-income countries and middle
      income countries. We analyzed data from the World Health Survey (2002-2004) on
      160,099 participants from 49 low-income and middle-income countries by using
      random-intercept multilevel logistic regressions. We found a U-shaped
      relationship between BMI and poor self-rated health among both sexes in both low
      income and middle-income countries, but the relationship differed by sex in
      strength and direction between low-income countries and middle-income countries.
      Differential perception of body weight and general health might explain some of
      the observed sex differences. 

PMID- 26292063
TI  - Tobacco Use Screening and Counseling During Hospital Outpatient Visits Among US
      Adults, 2005-2010.
AB  - INTRODUCTION: Physicians and health care providers play an important role in
      educating their patients about the health risks of tobacco use and in providing
      effective cessation interventions. Little is known about these practices in
      hospital outpatient settings. The objective of the study was to assess the
      prevalence, correlates, and trends of tobacco use screening and cessation
      assistance offered to US adults during their hospital outpatient clinic visits.
      METHODS: Data for aggregated hospital outpatient visits among patients aged 18
      years or older (N = 148,727) from the 2005-2010 National Hospital Ambulatory
      Medical Care Survey were analyzed. Tobacco use screening was defined as
      documentation of screening for either current tobacco use (cigarettes, cigars,
      snuff, or chewing tobacco) or no current use on the patient record form. Tobacco
      cessation assistance was defined as documentation of either tobacco counseling or
      cessation medications. RESULTS: Tobacco use screening was reported for 63.0%
      (estimated 271 million visits) of hospital outpatient visits, and cessation
      assistance was reported for 24.5% (estimated 17.1 million visits) of visits among
      current tobacco users. From 2005 through 2010, tobacco use screening (P for trend
      = .06) and cessation assistance (P for trend = .17) did not change significantly.
      CONCLUSION: From 2005 through 2010, more than one-third of hospital outpatient
      visits had no screening for tobacco use, and among current tobacco users, only 1
      in 4 received any cessation assistance. Health care providers should consistently
      identify and document their patients' tobacco use status and provide them with
      appropriate tobacco cessation assistance. Opportunities also exist to expand the
      coverage for tobacco cessation.

PMID- 26292065
TI  - Prevalence, Disparities, and Trends in Obesity and Severe Obesity Among Students
      in the School District of Philadelphia, Pennsylvania, 2006-2013.
AB  - INTRODUCTION: Recent analyses suggest that increases in rates of childhood
      obesity have plateaued nationally and may be decreasing among certain populations
      and communities, including Philadelphia, Pennsylvania. We examined 7 years of
      data, including 3 years not previously reported, to assess recent trends in major
      demographic groups. METHODS: We analyzed nurse-measured data from the School
      District of Philadelphia for school years 2006-07 through 2012-13 to assess
      trends in obesity (body mass index [BMI] >=95th percentile) and severe obesity
      (BMI >=120% of the 95th percentile) among all children aged 5 to 18 years for
      whom measurements were recorded. RESULTS: Over 7 school years, the prevalence of
      childhood obesity declined from 21.7% to 20.3% (P = .01); the prevalence of
      severe obesity declined from 8.5% to 7.3% (P < .001). Declines were larger among
      boys than among girls and among African Americans and Asians than among non
      Hispanic whites and Hispanics. Over the final 3 years of study, the prevalence of
      obesity continued to decrease significantly among boys (including African
      Americans and Asians) but increased significantly among Hispanic girls and girls
      in grades kindergarten through 5. At the end of the study period, Hispanics had
      the highest prevalence of obesity among boys (25.9%) and girls (23.0%). The
      prevalence of severe obesity continued to trend downward in boys and decrease
      significantly among girls (including African American girls) but remained highest
      among Hispanic boys (10.1%) and African American girls (8.3%). CONCLUSION: The
      prevalence of obesity and severe obesity continued to decline among children in
      Philadelphia, but in some groups initial reductions were reversed in the later
      period. Further monitoring, community engagement, and targeted interventions are
      needed to address childhood obesity in urban communities.

PMID- 26292066
TI  - Docking studies of flavonoid compounds as inhibitors of beta-ketoacyl acyl
      carrier protein synthase I (Kas I) of Escherichia coli.
AB  - Escherichia coli is one of the most frequent causes of many common bacterial
      infections, including cholecystitis, bacteremia, cholangitis, urinary tract
      infection (UTI), traveler's diarrhea and other clinical infections such as
      neonatal meningitis and pneumonia. The fatty acid biosynthesis is essential for
      the bacterial viability and growth. There are three types of beta-ketoacyl acyl
      carrier protein synthase (KAS) which are important for overcoming the bacterial
      resistance problem. beta-ketoacyl acyl carrier protein synthase I (KAS I) is
      member of the condensing enzyme family, which is a key catalyst in bacterial
      fatty acid biosynthesis, and thus an attractive target for novel antibioticsis
      related to the elongation of unsaturated fatty acids in bacterial fatty acid
      synthesis and can be a good therapeutic target of designing novel antibiotics. In
      this report, we performed docking study of E. coli (KAS I) and 50 flavonoids. Out
      of these 50 flavonoids, there are two compounds, genistein and isorhamnetin, that
      showed the superior binding energy while fully satisfying the conditions of drug
      likeliness. The predicted binding energy of genistein and isorhamnetin toward KAS
      I are -135.76kcal/mol and -132.42kcal/mol, respectively. These energies favorably
      compare to the biding energy of known drugs thiolactomicin and cerulenin that are
      -90.26kcal/mol and -99.64kcal/mol, respectively. The method used was docking with
      the selected E. coli (KAS I-PDB ID-1FJ4) using iGemdock. This was also found to
      obey the Lipinski's guidelines of five and to show the drug likeliness and
      bioavailability. 

PMID- 26292068
TI  - Improved Device Performance of Polymer Solar Cells by Using a Thin Light
      harvesting-Complex Modified ZnO Film as the Cathode Interlayer.
AB  - In this study, a high-performance inverted polymer solar cell (PSC) has been
      fabricated by incorporating a zinc oxide (ZnO)/light-harvesting complex II
      (LHCII) stacked structure as the cathode interlayer. The LHCII not only smoothens
      the film surface of ZnO, improves the contact between ZnO and the photoactive
      layer, but also suppresses the charge carrier recombination at the interface,
      hence all the device parameters of PTB7-based solar cells are simultaneously
      improved, yielding higher power conversion efficiency (PCE) up to 9.01% compared
      with the control one (PCE 8.01%). And the thin LHCII modification layer also
      presents similar positive effects in the PTB7-Th:PC71BM system (PCE from 8.31% to
      9.60%). These results put forward a facile approach to the interfacial
      modification in high-performance PSCs and provide new insight into developing and
      utilizing inexpensive and environmentally friendly materials from the fields of
      biological photosynthesis. 

PMID- 26292067
TI  - Twenty Years of Active Bacterial Core Surveillance.
AB  - Active Bacterial Core surveillance (ABCs) was established in 1995 as part of the
      Centers for Disease Control and Prevention Emerging Infections Program (EIP)
      network to assess the extent of invasive bacterial infections of public health
      importance. ABCs is distinctive among surveillance systems because of its large,
      population-based, geographically diverse catchment area; active laboratory-based
      identification of cases to ensure complete case capture; detailed collection of
      epidemiologic information paired with laboratory isolates; infrastructure that
      allows for more in-depth investigations; and sustained commitment of public
      health, academic, and clinical partners to maintain the system. ABCs has directly
      affected public health policies and practices through the development and
      evaluation of vaccines and other prevention strategies, the monitoring of
      antimicrobial drug resistance, and the response to public health emergencies and
      other emerging infections. 

PMID- 26292070
TI  - Proteome-wide identification of SUMO modification sites by mass spectrometry.
AB  - The protein called 'small ubiquitin-like modifier' (SUMO) is post-translationally
      linked to target proteins at the E-amino group of lysine residues. This
      'SUMOylation' alters the behavior of the target protein, a change that is
      utilized to regulate diverse cellular processes. Understanding the target
      specific consequences of SUMO modification requires knowledge of the location of
      conjugation sites, and we have developed a straightforward protocol for the
      proteome-wide identification of SUMO modification sites using mass spectrometry
      (MS). The approach described herein requires the expression of a mutant form of
      SUMO, in which the residue preceding the C-terminal Gly-Gly (diGly) is replaced
      with a lysine (SUMO(KGG)). Digestion of SUMO(KGG) protein conjugates with
      endoproteinase Lys-C yields a diGly motif attached to target lysines. Peptides
      containing this adduct are enriched using a diGly-Lys (K-E-GG)-specific antibody
      and identified by MS. This diGly signature is characteristic of SUMO(KGG)
      conjugation alone, as no other ubiquitin-like protein (Ubl) yields this adduct
      upon Lys-C digestion. We have demonstrated the utility of the approach in
      SUMOylation studies, but, in principle, it may be adapted for the site-specific
      identification of proteins modified by any Ubl. Starting from cell lysis, this
      protocol can be completed in ~5 d. 

PMID- 26292069
TI  - Melatonin attenuates MPTP-induced neurotoxicity via preventing CDK5-mediated
      autophagy and SNCA/alpha-synuclein aggregation.
AB  - Autophagy is involved in the pathogenesis of neurodegenerative diseases including
      Parkinson disease (PD). However, little is known about the regulation of
      autophagy in neurodegenerative process. In this study, we characterized aberrant
      activation of autophagy induced by neurotoxin 1-methyl-4-phenyl-1, 2, 3, 6
      tetrahydropyridine (MPTP) and demonstrated that melatonin has a protective effect
      on neurotoxicity. We found an excessive activation of autophagy in monkey brain
      tissues and C6 cells, induced by MPTP, which is mediated by CDK5 (cyclin
      dependent kinase 5). MPTP treatment significantly reduced total dendritic length
      and dendritic complexity of cultured primary cortical neurons and melatonin could
      reverse this effect. Decreased TH (tyrosine hydroxylase)-positive cells and
      dendrites of dopaminergic neurons in the substantia nigra pars compacta (SNc)
      were observed in MPTP-treated monkeys and mice. Along with decreased TH protein
      level, we observed an upregulation of CDK5 and enhanced autophagic activity in
      the striatum of mice with MPTP injection. These changes could be salvaged by
      melatonin treatment or knockdown of CDK5. Importantly, melatonin or knockdown of
      CDK5 reduced MPTP-induced SNCA/alpha-synuclein aggregation in mice, which is
      widely thought to trigger the pathogenesis of PD. Finally, melatonin or knockdown
      of CDK5 counteracted the PD phenotype in mice induced by MPTP. Our findings
      uncover a potent role of CDK5-mediated autophagy in the pathogenesis of PD, and
      suggest that control of autophagic pathways may provide an important clue for
      exploring potential target for novel therapeutics of PD. 

PMID- 26292071
TI  - Quantitative measurement of transcriptional inhibition and mutagenesis induced by
      site-specifically incorporated DNA lesions in vitro and in vivo.
AB  - Aberrant transcription induced by DNA damage may confer risk for the development
      of cancer and other human diseases. Traditional methods for measuring lesion
      induced transcriptional alterations often involve extensive colony screening and
      DNA sequencing procedures. Here we describe a protocol for the quantitative
      assessment of the effects of DNA lesions on the efficiency and fidelity of
      transcription in vitro and in mammalian cells. The method is also amenable to
      investigating the influence of specific DNA repair proteins on the biological
      response toward DNA damage during transcription by manipulating their gene
      expression. Specifically, we present detailed, step-by-step procedures, including
      DNA template preparation, in vitro and in vivo transcription, RNA purification,
      reverse-transcription PCR (RT-PCR) and restriction digestion of RT-PCR products.
      Analyses of restriction fragments of interest are performed by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) and polyacrylamide gel
      electrophoresis (PAGE). The entire procedure described in this protocol can be
      completed in 15-20 d. 

PMID- 26292072
TI  - Defining human dendritic cell progenitors by multiparametric flow cytometry.
AB  - Human dendritic cells (DCs) develop from progressively restricted bone marrow
      (BM) progenitors: these progenitor cells include granulocyte, monocyte and DC
      progenitor (GMDP) cells; monocyte and DC progenitor (MDP) cells; and common DC
      progenitor (CDP) and DC precursor (pre-DC) cells. These four DC progenitors can
      be defined on the basis of the expression of surface markers such as CD34 and
      hematopoietin receptors. In this protocol, we describe five multiparametric flow
      cytometry panels that can be used as a tool (i) to simultaneously detect or
      phenotype the four DC progenitors, (ii) to isolate DC progenitors to enable in
      vitro differentiation or (iii) to assess the in vitro differentiation and
      proliferation of DC progenitors. The entire procedure from isolation of cells to
      flow cytometry can be completed in 3-7 h. This protocol provides optimized
      antibody panels, as well as gating strategies, for immunostaining of BM and cord
      blood specimens to study human DC hematopoiesis in health, disease and vaccine
      settings. 

PMID- 26292073
TI  - Diagnosis of iron-deficient states.
AB  - The diagnosis of iron deficiency anemia is typically straightforward, especially
      when classic biochemical and hematological changes are present in a subject at
      risk. It can be challenging in the presence of diseases or when it is due to
      inherited defects of iron metabolism. The identification of iron deficiency prior
      to anemia development is also difficult. New hematological parameters such as
      reticulocyte Hb content have expanded the classic ones such as MCV, MCH and MCHC.
      A variety of hematology analyzers now provide novel parameters to assess cellular
      hypochromia and microcytosis in both reticulocytes and mature red blood cells.
      The repertoire of biochemical markers has also been expanded, with iron,
      transferrin and ferritin being supplemented by circulating transferrin receptor
      and hepcidin. Molecular identification of functional variants of key iron
      metabolism determinants has provided explanations for the heritability of some
      iron metabolism biomarkers. Genetic defects in some of these molecules are
      responsible for hereditary microcytic anemias, also called atypical microcytic
      anemias. In this review, we examine the most significant hematological and
      biochemical markers for iron metabolism, as well as relevant genetic
      polymorphisms and defects affecting iron handling. 

PMID- 26292074
TI  - How many biomarkers to discriminate neurodegenerative dementia?
AB  - A number of cerebrospinal fluid (CSF) biomarkers are currently used for the
      diagnosis of dementia. Opposite changes in the level of amyloid-beta(1-42) versus
      total tau and phosphorylated-tau181 in the CSF reflect the specific pathology of
      Alzheimer's disease (AD) in the brain. This panel of biomarkers has proven to be
      effective to differentiate AD from controls and from the major types of
      neurodegenerative dementia, and to evaluate the progression from mild cognitive
      impairment to AD. In the absence of specific biomarkers reflecting the
      pathologies of the other most common forms of dementia, such as Lewy Body
      disease, Frontotemporal lobar degeneration, Creutzfeldt-Jakob disease, etc., the
      evaluation of biomarkers of AD pathology is used, attempting to exclude rather
      than to confirm AD. Other biomarkers included in the common clinical practice do
      not clearly relate to the underlying pathology: progranulin (PGRN) is a selective
      marker of frontotemporal dementia with mutations in the PGRN gene; the 14-3-3
      protein is a highly sensitive and specific marker for Creutzfeldt-Jakob disease,
      but has to be used carefully in differentiating rapid progressive dementia; and
      alpha-synuclein is an emerging candidate biomarker of the different forms of
      synucleinopathy. This review summarizes several biomarkers of neurodegenerative
      dementia validated based on the neuropathological processes occurring in brain
      tissue. Notwithstanding the paucity of pathologically validated biomarkers and
      their high analytical variability, the combinations of these biomarkers may well
      represent a key and more precise analytical and diagnostic tool in the complex
      plethora of degenerative dementia.

PMID- 26292075
TI  - Barriers to hospital-based clinical adoption of point-of-care testing (POCT): A
      systematic narrative review.
AB  - Recent advances in areas such as biomarker discovery and microfluidic device
      fabrication have allowed clinical testing to be moved ever closer to the site of
      patient care. The development of a range of point-of-care testing (POCT) devices
      that seek to provide the clinician with diagnostic test results more rapidly
      offer the opportunity to enhance the quality of care for the individual patient
      and the population at large. However, there are indications that, notwithstanding
      advances in the technologies that underpin the utility of POCT, their clinical
      uptake and utilization is less than might be expected. Moreover, the nature and
      relative importance of the barriers identified as being impediments to their more
      widespread adoption are not well understood. This article reports the findings
      from a systematic narrative review of published literature sources over the
      period 2000 to January 2014 to identify and categorize the various barriers to
      adoption of POCT devices within the clinical environment. Data from a total of
      six electronic bibliographic databases were accessed and these searches were
      supplemented by scrutinizing the reference lists within the key articles
      identified. A set of 49 key articles were assessed in detail and from these four
      specific categories of barrier to adoption of POCT were identified.
      Identification and categorization of these barriers, along with an assessment of
      their significance to clinical practice, is seen as necessary for developing real
      solutions to ensure appropriate and effective POCT uptake. The most prevalent
      categories were those associated with the economics of adoption and quality
      assurance and regulatory issues, each which were reflected in 65% of the
      literature articles reviewed. Device performance and data management issues were
      cited in 51% of the publications. Staff and operational issues were found within
      35% of articles. The most significant barriers identified concerned higher cost
      per test of POCT in comparison to centralized testing; difficulties in gauging
      the cost-effectiveness of a POCT system and the complexities in making cost
      comparisons with centralized systems; quality assurance issues relating to the
      operation of devices by untrained/non-competent staff; reduced analytical
      performance of POCT devices in comparison to centralized methods; and
      connectivity and data management issues. Complex regulatory requirements for
      accreditation, staff satisfaction levels and friction between clinical groups and
      the effect on existing clinical pathways by alternative testing methods were also
      identified as being significant concerns.

PMID- 26292076
TI  - Adipocyte size as a determinant of metabolic disease and adipose tissue
      dysfunction.
AB  - Obesity is a heterogeneous disease and is associated with comorbidities such as
      type 2 diabetes mellitus, cardiovascular disease and cancer. Several studies have
      examined the role of dysfunctional adipose tissue in the pathogenesis of obesity,
      highlighting the contrasting properties and impact of distinct fat compartments,
      sometimes with contradictory results. Dysfunctional adipose tissue involves
      enlargement, or hypertrophy, of pre-existing fat cells, which is thought to
      confer increases in cardiometabolic risk, independent of the level of obesity per
      se. In this article, we critically analyze available literature that examined the
      ability of adipocyte cell size to predict metabolic disease and adipose tissue
      dysfunction in humans. Many studies demonstrate that increased fat cell size is a
      significant predictor of altered blood lipid profiles and glucose-insulin
      homeostasis independent of adiposity indices. The contribution of visceral
      adiposity to these associations appears to be of particular importance. However,
      available studies are not unanimous and many fat depot-specific aspects of the
      relationship between increased fat cell size and cardiometabolic risk or
      parameters of adipose tissue dysfunction are still unresolved. Methodological
      factors such as the approach used to express the data may represent significant
      confounders in these studies. Additional studies should consider the fact that
      the relationship between fat cell size and common adiposity indices is non
      linear, particularly when reaching the obese range. In conclusion, our analysis
      demonstrates that fat cell size is a significant predictor of the cardiometabolic
      alterations related to obesity. We propose that adipocyte hypertrophy, especially
      in the visceral fat compartment, may represent a strong marker of limited
      hyperplasic capacity in subcutaneous adipose tissues, which in turn is associated
      with the presence of numerous cardiometabolic alterations. 

PMID- 26292077
TI  - Ketamine-Propofol Versus Propofol Alone for Procedural Sedation in the Emergency
      Department: A Systematic Review and Meta-analysis.
AB  - OBJECTIVES: Propofol is an agent commonly used for procedural sedation and
      analgesia (PSA) in the emergency department (ED), but it can cause respiratory
      depression and hypotension. The combination of ketamine-propofol (K-P) is an
      alternative that theoretically provides a reduction in adverse events compared to
      propofol. The primary objective of this review was to determine if K-P has a
      lower frequency of adverse respiratory events in patients undergoing PSA in the
      ED than propofol alone. Secondary objectives were to compare the proportion of
      overall adverse events, sedation time, procedure time, and recovery time between
      K-P and propofol. METHODS: Electronic searches of Medline, EMBASE, Cochrane
      Central Register of Controlled Trials, and CINAHL were conducted and reference
      lists were hand-searched. Randomized controlled trials (RCTs) published in
      English comparing the use of K-P to propofol alone for PSA in the ED were
      included. RESULTS: Six RCTs were included with a combined total of 932 patients
      (K-P = 520, propofol = 412). Five RCTs reported the proportion of adverse
      respiratory events; the pooled estimate revealed fewer adverse respiratory events
      with K-P compared to propofol (29.0% vs. 35.4%; risk ratio [RR] = 0.82; 95%
      confidence interval [CI] = 0.68 to 0.99). There was no significant difference
      with respect to the proportion of overall adverse events (38.8% vs. 42.5%; RR =
      0.88; 95% CI = 0.75 to 1.04). Procedure time was similar when the groups were
      compared. CONCLUSIONS: The premise of combining ketamine with propofol is based
      on the many synergies that theoretically exist between these two agents. In this
      study, K-P had a lower frequency of adverse respiratory events in patients
      undergoing PSA in the ED compared to propofol alone.

PMID- 26292078
TI  - Adsorption and degradation of phenoxyalkanoic acid herbicides in soils: A review.
AB  - The primary aim of the present review on phenoxyalkanoic acid herbicides-2-(2,4
      dichlorophenoxy) acetic acid (2,4-D), 2-(4-chloro-2-methylphenoxy) acetic acid
      (MCPA), (2R)-2-(2,4-dichlorophenoxy) propanoic acid (dichlorprop-P), (2R)-2-(4
      chloro-2-methylphenoxy) propanoic acid (mecoprop-P), 4-(2,4-dichlorophenoxy)
      butanoic acid (2,4-DB), and 4-(4-chloro-2-methylphenoxy) butanoic acid (MCPB)-was
      to compare the extent of their adsorption in soils and degradation rates to
      assess their potential for groundwater contamination. The authors found that
      adsorption decreased in the sequence of 2,4-DB > 2,4-D > MCPA > dichlorprop-P >
      mecoprop-P. Herbicides are predominantly adsorbed as anions-on organic matter and
      through a water-bridging mechanism with adsorbed Fe cations-and their neutral
      forms are adsorbed mainly on organic matter. Adsorption of anions of 2,4-D, MCPA,
      dichlorprop-P, and mecoprop-P is inversely correlated with their lipophilicity
      values, and modeling of adsorption of the compounds based on this relationship is
      possible. The predominant dissipation mechanism of herbicides in soils is
      bacterial degradation. The contribution of other mechanisms, such as degradation
      by fungi, photodegradation, or volatilization from soils, is much smaller. The
      rate of bacterial degradation decreased in the following order: 2,4-D > MCPA >
      mecoprop-P > dichlorprop-P. It was found that 2,4-D and MCPA have the lowest
      potential for leaching into groundwater and that mecoprop-P and dichlorprop-P
      have slightly higher potential. Because of limited data on adsorption and
      degradation of 2,4-DB and MCPB, estimation of their leaching potential was not
      possible.

PMID- 26292079
TI  - Characteristic length of the knotting probability revisited.
AB  - We present a self-avoiding polygon (SAP) model for circular DNA in which the
      radius of impermeable cylindrical segments corresponds to the screening length of
      double-stranded DNA surrounded by counter ions. For the model we evaluate the
      probability for a generated SAP with N segments having a given knot K through
      simulation. We call it the knotting probability of a knot K with N segments for
      the SAP model. We show that when N is large the most significant factor in the
      knotting probability is given by the exponentially decaying part exp(-N/NK),
      where the estimates of parameter NK are consistent with the same value for all
      the different knots we investigated. We thus call it the characteristic length of
      the knotting probability. We give formulae expressing the characteristic length
      as a function of the cylindrical radius rex, i.e. the screening length of double
      stranded DNA. 

PMID- 26292080
TI  - A Prospective Cohort Quality Improvement Study to Reduce the Time to Antibiotics
      for New Fever in Neutropenic Pediatric Oncology Inpatients.
AB  - BACKGROUND: Fever and neutropenia (F&N) is a pediatric oncology emergency due to
      the risk of disseminated infection. Quality improvement (QI) efforts to improve
      time to antibiotics for F&N in the emergency department have been documented, but
      the issue has not been studied in the established inpatient setting. PROCEDURE:
      We undertook a prospective cohort QI study to decrease time to antibiotics for
      neutropenic pediatric oncology inpatients with new fever to <60 min. Our key
      intervention was discussion of a plan in case of new fever, including
      antibiotic(s) to be started, for each patient on rounds. Timing for each step in
      the process, from fever identification to antibiotic administration, was measured
      through the electronic medical record for each fever event. RESULTS: The median
      time to antibiotics during the 3-three month intervention study period was 76.0
      min, although the distribution was skewed due to several long outliers (mean
      142.5, interquartile range 51-206, range 47-593 min). Time to antibiotics was
      significantly shorter when a fever contingency plan was documented in the most
      recent note than not (mean 102 vs. 254 min, P = 0.039). Over the total 2.75 year
      data-collection period, the quarterly percentage of patients receiving
      antibiotics within 60 min has improved from 35 to 65, whereas quarterly mean time
      to antibiotics has improved from 99 to 50 min. CONCLUSIONS: Daily discussion of a
      fever contingency plan appears effective in decreasing the time to antibiotics
      for neutropenic pediatric oncology inpatients with new fever, likely by
      circumventing the need for multi-level discussion of the antibiotic plan when
      fever is identified.

PMID- 26292081
TI  - Image signal-to-noise ratio estimation using adaptive slope nearest-neighbourhood
      model.
AB  - A new technique based on nearest neighbourhood method is proposed. In this paper,
      considering the noise as Gaussian additive white noise, new technique single
      image-based estimator is proposed. The performance of this new technique such as
      adaptive slope nearest neighbourhood is compared with three of the existing
      method which are original nearest neighbourhood (simple method), first-order
      interpolation method and shape-preserving piecewise cubic hermite autoregressive
      moving average. In a few cases involving images with different brightness and
      edges, this adaptive slope nearest neighbourhood is found to deliver an optimum
      solution for signal-to-noise ratio estimation problems. For different values of
      noise variance, the adaptive slope nearest neighbourhood has highest accuracy and
      less percentage estimation error. Being more robust with white noise, the new
      proposed technique estimator has efficiency that is significantly greater than
      those of the three methods. 

PMID- 26292083
TI  - Ambient air pollution, blood mitochondrial DNA copy number and telomere length in
      a panel of diabetes patients.
AB  - CONTEXT: Several previous studies proposed a link between particulate matter (PM)
      pollution and mitochondrial DNA copy number (MtDNAcn) and telomere length (TL).
      However, this evidence is quite limited and inconsistent, especially on how the
      particle size affects the associations and on whether there exists such an
      association with gaseous pollutants. OBJECTIVE: We aimed to investigate the short
      term associations of size-fractionated PM and gaseous pollutants with blood
      MtDNAcn and TL. METHODS: We conducted a longitudinal panel study involving 6
      repeated measurements among 35 Type 2 diabetes patients in Shanghai, China from
      April to June 2013. We measured the real-time concentrations of size-fractionated
      PM (0.25-10 MUm) and criteria gaseous pollutants. Blood MtDNAcn and TL were
      tested by a quantitative real-time PCR-based assay. Linear mixed-effect models
      were used to explore their short-term associations using multiple lag periods,
      after controlling for individual characteristics, time trends and weather
      conditions. RESULTS: In general, there were inverse but statistically non
      significant associations between all pollutants and MtDNAcn. Coarse PM appeared
      to be more closely linked with MtDNAcn than smaller PM. The associations between
      various air pollutants and TL were generally positive but very weak. There were
      no clear lag patterns for these associations. The associations between air
      pollutants and MtDNAcn and TL were strengthened but still not significant among
      those who did not take statins regularly. CONCLUSIONS: This study did not support
      short-term associations of PM or gaseous pollutants with blood MtDNAcn and TL in
      type 2 diabetes patients.

PMID- 26292082
TI  - Comparative teratogenicity analysis of valnoctamide, risperidone, and olanzapine
      in mice.
AB  - OBJECTIVES: Based on the recent findings from animal studies, it has been
      proposed that the therapeutic use of valnoctamide, an anxiolytic drug developed
      in the early 1960s, be extended to treat other neurological disorders such as
      epilepsy and bipolar disease. Given the scarcity of adequate data on its prenatal
      toxicity, a comparative teratogenicity study of valnoctamide and two of the most
      commonly used drugs to treat bipolar disorder, risperidone and olanzapine, was
      carried out in a mouse model system. METHODS: Pregnant dams were treated with the
      aforementioned three drugs at the dose levels calculated as an equal proportion
      of the respective LD50 values of these drugs. The main reproductive indices
      examined included the numbers of implantations and resorptions, viable and dead
      fetuses, and fetal gross, visceral and skeletal abnormalities. RESULTS: The
      outcomes of the present study indicated that olanzapine was the most teratogenic
      of the three drugs, inducing maternal-, embryo-, and fetotoxicity. Risperidone
      also exerted a significant prenatal toxicity, but its adverse effect was less
      pronounced than that induced by olanzapine. Valnoctamide did not show any
      teratogenic effect, even when used in relatively higher dosages than olanzapine
      and risperidone. The observed increased skeletal abnormalities in one of the
      valnoctamide treatment groups were nonspecific and, as such, signaled a modest
      developmental delay rather than an indication that the compound could induce
      structural malformations. CONCLUSIONS: Under our experimental conditions,
      valnoctamide demonstrated the lowest prenatal toxicity of the three tested drugs.

PMID- 26292084
TI  - Tungsten oxide nanowires grown on amorphous-like tungsten films.
AB  - Tungsten oxide nanowires have been synthesized by vacuum annealing in the range
      500-710  degrees C from amorphous-like tungsten films, deposited on a Si(100)
      substrate by pulsed laser deposition (PLD) in the presence of a He background
      pressure. The oxygen required for the nanowires formation is already adsorbed in
      the W matrix before annealing, its amount depending on deposition parameters.
      Nanowire crystalline phase and stoichiometry depend on annealing temperature,
      ranging from W18O49-Magneli phase to monoclinic WO3. Sufficiently long annealing
      induces the formation of micrometer-long nanowires, up to 3.6 MUm with an aspect
      ratio up to 90. Oxide nanowire growth appears to be triggered by the
      crystallization of the underlying amorphous W film, promoting their synthesis at
      low temperatures. 

PMID- 26292085
TI  - Loss and Gain of Natural Killer Cell Receptor Function in an African Hunter
      Gatherer Population.
AB  - Modulating natural killer cell functions in human immunity and reproduction are
      diverse interactions between the killer cell immunoglobulin-like receptors (KIR)
      of Natural Killer (NK) cells and HLA class I ligands on the surface of tissue
      cells. Dominant interactions are between KIR2DL1 and the C2 epitope of HLA-C and
      between KIR2DL2/3 and the C1 epitope of HLA-C. KhoeSan hunter-gatherers of
      Southern Africa represent the earliest population divergence known and are the
      most genetically diverse indigenous people, qualities reflected in their KIR and
      HLA genes. Of the ten KhoeSan KIR2DL1 alleles, KIR2DL1*022 and KIR2DL1*026 likely
      originated in the KhoeSan, and later were transmitted at low frequency to the
      neighboring Zulus through gene flow. These alleles arose by point mutation from
      other KhoeSan KIR2DL1 alleles that are more widespread globally. Mutation of
      KIR2DL1*001 gave rise to KIR2DL1*022, causing loss of C2 recognition and gain of
      C1 recognition. This makes KIR2DL1*022 a more avid and specific C1 receptor than
      any KIR2DL2/3 allotype. Mutation of KIR2DL1*012 gave rise to KIR2DL1*026, causing
      premature termination of translation at the end of the transmembrane domain. This
      makes KIR2DL1*026 a membrane-associated receptor that lacks both a cytoplasmic
      tail and signaling function. At higher frequencies than their parental allotypes,
      the combined effect of the KhoeSan-specific KIR2DL1*022 and KIR2DL1*026 is to
      reduce the frequency of strong inhibitory C2 receptors and increase the frequency
      of strong inhibitory C1 receptors. Because interaction of KIR2DL1 with C2 is
      associated with risk of pregnancy disorder, these functional changes are
      potentially advantageous. Whereas all other KhoeSan KIR2DL1 alleles are present
      on a wide diversity of centromeric KIR haplotypes, KIR2DL1*026 is present on a
      single KIR haplotype and KIR2DL1*022 is present on two very similar haplotypes.
      The high linkage disequilibrium across their haplotypes is consistent with a
      recent emergence for these KIR2DL1 alleles that have distinctive functions. 

PMID- 26292086
TI  - uPAR Expression Pattern in Patients with Urothelial Carcinoma of the Bladder-
      Possible Clinical Implications.
AB  - The objective of the present study was to confirm the expression and localisation
      pattern of the urokinase-type plasminogen activator receptor (uPAR) focusing on
      its possible clinical relevance in patients with urothelial neoplasia of the
      bladder. uPAR is a central molecule in tissue remodelling during cancer invasion
      and metastasis and is an established prognostic marker in various cancer diseases
      other than bladder cancer. Formalin-fixed and paraffin-embedded tumour-tissue
      blocks from 186 patients treated with radical cystectomy were analysed. uPAR
      expression was scored as either negative or positive as well as by the actual
      score. Separate scores were obtained for cancer cells, macrophages and
      myofibroblasts at the invasive front and in tumour core. We were able to confirm,
      in an independent patient cohort, the tissue expression and localisation pattern
      of uPAR as investigated by Immunohistochemistry as well as a significant
      association between uPAR positivity and increasing tumour stage and tumour grade.
      This demonstrates the robustness of our previous and current findings. In
      addition the association between uPAR positive myofibroblasts and poor survival
      was reproduced. The highest hazard ratios for survival were seen for uPAR
      positive myofibroblasts both at the invasive front and in tumour core. Evaluating
      uPAR expression by the actual score showed a significant association between uPAR
      positive myofibroblasts in tumour core and an increased risk of cancer specific
      mortality. Our investigations have generated new and valuable biological
      information about the cell types being involved in tumour invasion and
      progression through the plasminogen activation system. 

PMID- 26292087
TI  - Probing the Structure, Composition, and Spatial Distribution of Ligands on Gold
      Nanorods.
AB  - The structure and size of ligands attached to the surfaces of gold nanorods, such
      as adsorbed surfactants or grafted polymers, are important considerations that
      facilitate the use of such nanoparticles in the human body, in advanced materials
      for energy harvesting, or in devices for single molecule detection. Here, we
      report small-angle neutron scattering (SANS) measurements from surfactant or
      poly(ethylene glycol) (PEG) coated gold nanorods in solution, which
      quantitatively determine the location, structure, and composition of these
      surface layers. In addition, by synthesizing gold nanorods using seed crystals
      which are coated with deuterated cetyltrimethylammonium bromide (dCTAB), we are
      able to exploit the isotopic sensitivity of SANS to study, for the first time,
      the retention of surfactant from the seed crystals to the final gold nanorod
      product, finding that very little exchange of the deuterated with hydrogenated
      surfactant occurs. Finally, we demonstrate that, when Au NRs are PEGylated using
      standard techniques, the surfactant bilayer remains intact, and while mass
      spectrometry detects the presence of both surfactant and PEG, the composition as
      measured from SANS is predominantly that of the surfactant. These measurements
      not only provide new insight into the synthesis and functionalization of gold
      nanorods but provide a quantitative picture of the structure of grafted polymer
      and surfactant layers on gold nanorod surfaces which has implications for the
      fabrication of plasmonic and biomedical materials. 

PMID- 26292088
TI  - Trends in urinary incontinence in women between 4 and 24 months postpartum in the
      EDEN cohort.
AB  - OBJECTIVE: Our aim was to study risk factors associated with the prevalence,
      incidence and remission of urinary incontinence (UI) between 4 and 24 months
      postpartum. DESIGN: Longitudinal study (EDEN cohort). SETTING: Two French
      university hospitals. POPULATION: 1643 women completed the questionnaire at 4
      months and 1409 at 24 months, including 1354 who completed it both times.
      METHODS: Multivariate analyses identified risk factors for UI prevalence at 24
      months postpartum, persistent UI versus remission, de novo UI versus continence,
      de novo UI versus persistent UI, and changes in IU severity between 4 and 24
      months postpartum. MAIN OUTCOME MEASURES: Postnatal UI and Sandvik UI severity
      score. RESULTS: UI prevalence was 20.7% (340/1643) at 4 months and 19.9%
      (280/1409) at 24 months. Significant factors associated with UI at 24 months were
      older age [OR = 1.07/year (95%CI 1.04-1.11)], BMI [2.35 (1.44-3.85) >=30 versus
      <25 kg/m2], higher parity [1.77 (1.14-2.76) >=3 versus 1], breastfeeding [1.54
      (1.08-2.19) >=3 versus < 3 months], pregnant at follow up [3.44 (2.25-5.26)], and
      caesarean delivery [0.62 (0.40-0.97) versus vaginal] [OR, odds ratio (CI,
      confidence interval)]. The likelihood of UI remission at 24 months was 51.9%
      (149/287). Caesarean delivery was associated with increased likelihood of UI
      remission [0.43 (0.19-0.97)]. The risk of de novo UI at 24 months was 12.5%
      (135/1067) and was associated with a new pregnancy [3.63 (2.13-6.20)].
      CONCLUSIONS: Between 4 and 24 months postpartum UI, remission occurred in half of
      the cases. These postnatal UI changes were essentially related to mode of
      delivery and subsequent pregnancy. TWEETABLE ABSTRACT: Postnatal urinary
      incontinence progression is mostly related with mode of delivery and subsequent
      pregnancy.

PMID- 26292089
TI  - Correction: Circadian Cycle-Dependent MeCP2 and Brain Chromatin Changes.

PMID- 26292090
TI  - Levels of Neopterin and other Inflammatory Markers in Obese and Non-Obese
      Patients with Polycystic Ovary Syndrome.
AB  - BACKGROUND: We aimed to measure the levels of inflammatory markers and neopterin
      in obese and non-obese patients with PCOS by using 2 separate control groups with
      matching body mass index (BMI). MATERIAL AND METHODS: A total of 60 women of
      reproductive age with (n=30) and without (n=30) PCOS were included in this study.
      Based on their BMI, patients with PCOS were divided into 2 groups as obese (n=15)
      and non-obese (n=15) PCOS groups. In addition, 2 BMI-matched control groups were
      formed. Neopterin, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6),
      C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (N/L ratio), and vitamin
      B12 were assessed by complete blood count. RESULTS: No significant difference was
      found between patients with PCOS and control subjects in neopterin, IL-6, TNF
      alpha, and CRP levels. However, N/L ratio levels were significantly higher (p
      0.045) and vitamin B12 levels were significantly lower (p 0.033) in patients with
      PCOS compared to control subjects. No statistically significant difference was
      found between obese and non-obese patients with PCOS and control subjects in
      neopterin, IL-6, TNF-alpha, and N/L ratio levels. However, CRP levels were
      significantly higher in obese patients with PCOS compared to obese control
      subjects (p 0.007). CONCLUSIONS: It can be concluded that inflammatory activity
      is increased in patients with PCOS, can lead to an increased risk for
      atherosclerosis, and this increase is not caused by obesity but rather by the
      polycystic ovary syndrome itself. However, studies with larger sample sizes are
      needed in this area.

PMID- 26292091
TI  - Isolation of the PCB-degrading bacteria Mesorhizobium sp. ZY1 and its combined
      remediation with Astragalus sinicus L. for contaminated soil.
AB  - A bacterial strain ZY1 capable of utilizing PCBs as its carbon source was
      isolated from the root nodules of Chinese milk vetch (Astragalus sinicus L.). The
      strain was identified as Mesorhizobium sp. according to its physiological
      biochemical properties and the analysis of its 16S rRNA gene sequence. When the
      initial OD600 was 0.15, 62.7% of 15 mg L(-1) 3,3',4,4'-TCB in a liquid culture
      was degraded by Mesorhizobium sp. ZY1 within 10 days. Mesorhizobium sp. ZY1 also
      greatly increased the biotransformation of soil PCBs. Pot experiments indicated
      that the soil PCB concentrations of a single incubation of strain ZY1 (R) and a
      single planting of A. sinicus (P) decreased by 20.5% and 23.0%, respectively, and
      the concentration of PCBs in soil treated with A. sinicus and strain ZY1
      decreased by 53.1%. We also observed that A. sinicus-Mesorhizobium sp. ZY1
      treatment (PR) improved plant biomass and the concentration of PCBs in plants
      compared with a single A. sinicus planting treatment (P). The results suggest
      that the synergistic association between A. sinicus and PCBs-degrading
      Mesorhizobium sp. ZY1 can stimulate the phytoextraction of PCBs and the
      rhizosphere microflora to degrade PCBs, and might be a promising bioremediation
      strategy for PCB-contaminated soil.

PMID- 26292092
TI  - Transcriptome Analysis of Liangshan Pig Muscle Development at the Growth Curve
      Inflection Point and Asymptotic Stages Using Digital Gene Expression Profiling.
AB  - Animal growth curves can provide essential information for animal breeders to
      optimize feeding and management strategies. However, the genetic mechanism
      underlying the phenotypic differentiation between the inflection point and
      asymptotic stages of the growth curve is not well characterized. Here, we
      employed Liangshan pigs in stages of growth at the inflection point (under
      inflection point: UIP) and the two asymptotic stages (before the inflection
      point: BIP, after the inflection point: AIP) as models to survey global gene
      expression in the longissimus dorsi muscle using digital gene expression (DGE)
      tag profiling. We found Liangshan pigs reached maximum growth rate (UIP) at 163.6
      days of age and a weight of 134.6 kg. The DGE libraries generated 117 million
      reads of 5.89 gigabases in length. 21,331, 20,996 and 20,139 expressed
      transcripts were identified BIP, UIP and AIP, respectively. Among them, we
      identified 757 differentially expressed genes (DEGs) between BIP and UIP, and 271
      DEGs between AIP and UIP. An enrichment analysis of DEGs proved the immune system
      was strengthened in the AIP stage. Energy metabolism rate, global transcriptional
      activity and bone development intensity were highest UIP. Meat from Liangshan
      pigs had the highest intramuscular fat content and most favorable fatty acid
      composition in the AIP. Three hundred eighty (27.70%) specific expression genes
      were highly enriched in QTL regions for growth and meat quality traits. This
      study completed a comprehensive analysis of diverse genetic mechanisms underlying
      the inflection point and asymptotic stages of growth. Our findings will serve as
      an important resource in the understanding of animal growth and development in
      indigenous pig breeds. 

PMID- 26292093
TI  - Serum HER2 Is a Potential Surrogate for Tissue HER2 Status in Gastric Cancer: A
      Systematic Review and Meta-Analysis.
AB  - Determining the expression level of human epidermal growth factor receptor 2
      (HER2) in tumor tissue is of great importance for personalized therapy in gastric
      cancer. Although several studies have investigated whether serum HER2 can serve
      as a surrogate for tissue HER2 status, results have been inconsistent. We
      therefore performed a meta-analysis of published clinical studies in an attempt
      to address this problem. PubMed, Embase, Web of Science, the Cochrane Library and
      Science Direct were queried for eligible studies that could provide sufficient
      data to construct 2 * 2 contingency tables. The quality of the studies included
      in the meta-analysis was assessed in accordance with the revised Quality
      Assessment of Diagnostic Accuracy Studies (QUADAS-2) criteria. The pooled
      sensitivity, specificity and diagnostic odds ratio (DOR) were calculated for the
      eligible studies. The summary receiver operating characteristic (SROC) curve was
      constructed and the area under the SROC (AUSROC) was used to evaluate overall
      diagnostic performance. Eight studies comprising a total of 1170 participants
      were included in our meta-analysis. The pooled sensitivity, specificity and DOR
      were 0.39 (95% CI: 0.21-0.61), 0.98 (95% CI: 0.87-1.00), and 27 (95% CI: 9-81),
      respectively. The AUSROC was 0.77 (95% CI: 0.73-0.80) and Deeks funnel plot
      suggested the absence of publication bias (p = 0.91). Meta-regression analysis
      indicated that threshold effect was the main source of heterogeneity. Assays for
      evaluating serum HER2 levels are highly specific and demonstrate moderate
      diagnostic performance for HER2 tissue status in gastric cancer. 

PMID- 26292094
TI  - Optically Trapped Surface-Enhanced Raman Probes Prepared by Silver Photoreduction
      to 3D Microstructures.
AB  - 3D microstructures partially covered by silver nanoparticles have been developed
      and tested for surface-enhanced Raman spectroscopy (SERS) in combination with
      optical tweezers. The microstructures made by two-photon polymerization of SU-8
      photoresist were manipulated in a dual beam optical trap. The active area of the
      structures was covered by a SERS-active silver layer using chemically assisted
      photoreduction from silver nitrate solutions. Silver layers of different grain
      size distributions were created by changing the photoreduction parameters and
      characterized by scanning electron microscopy. The structures were tested by
      measuring the SERS spectra of emodin and hypericin. 

PMID- 26292095
TI  - Interleukin-18 Down-Regulates Multidrug Resistance-Associated Protein 2
      Expression through Farnesoid X Receptor Associated with Nuclear Factor Kappa B
      and Yin Yang 1 in Human Hepatoma HepG2 Cells.
AB  - Multidrug resistance-associated protein 2 (MRP2) plays an important role in bile
      acid metabolism by transporting toxic organic anion conjugates, including
      conjugated bilirubin, glutathione, sulfate, and multifarious drugs. MRP2
      expression is reduced in cholestatic patients and rodents. However, the molecular
      mechanism of MRP2 down-regulation remains elusive. In this report, we treated
      human hepatoma HepG2 cells with interleukin-18 (IL-18) and measured the
      expression of MRP2, nuclear factor kappa B (NF-kappaB), farnesoid X receptor
      (FXR), and the transcription factor Yin Yang 1 (YY1) by quantitative real-time
      quantitative polymerase chain reaction (PCR) and western blotting. We found that
      expression of MRP2 was repressed by IL-18 at both the mRNA and protein levels in
      a dose- and time-dependent manner. Furthermore, the activated NF-kappaB pathway
      increased YY1 and reduced FXR. These changes were all attenuated in HepG2 cells
      with knockdown of the NF-kappaB subunit, p65. The reduced expression of FXR and
      MRP2 in HepG2 cells that had been caused by IL-18 treatment was also attenuated
      by YY1 knockdown. We further observed significantly elevated IL-18, NF-kappaB,
      and YY1 expression and decreased FXR and MRP2 expression in bile duct-ligated
      Sprague Dawley rat livers. Chromatin immunoprecipitation assays also showed that
      FXR bound to the promoter region in MRP2 was less abundant in liver extracts from
      bile duct-ligated rats than sham-operated rats. Our findings indicate that IL-18
      down-regulates MRP2 expression through the nuclear receptor FXR in HepG2 cells,
      and may be mediated by NF-kappaB and YY1. 

PMID- 26292096
TI  - Body Mass Parameters, Lipid Profiles and Protein Contents of Zebrafish Embryos
      and Effects of 2,4-Dinitrophenol Exposure.
AB  - Morphology and physiology of fish embryos undergo dramatic changes during their
      development until the onset of feeding, supplied only by endogenous yolk
      reserves. For obtaining an insight how these restructuring processes are
      reflected by body mass related parameters, dry weights (dw), contents of the
      elements carbon and nitrogen and lipid and protein levels were quantified in
      different stages within the first four days of embryo development of the
      zebrafish (Danio rerio). The data show age dependent changes in tissue
      composition. Dry weights decreased significantly from 79MUgdw/egg at 0hours post
      fertilization (hpf) to 61 MUgdw/egg after 96 hpf. The amounts of total carbon
      fluctuated between 460 mg g-1 and 540 mg g-1 dw, nitrogen was at about 100 mg g-1
      dw and total fatty acids were between 48-73 mg g-1 dw. In contrast to these
      parameters that remained relatively constant, the protein content, which was 240
      mg g-1 at 0 hpf, showed an overall increase of about 40%. Comparisons of intact
      eggs and dechorionated embryos at stages prior to hatching (24, 30, 48 hpf)
      showed that the differences seen for dry weight and for carbon and nitrogen
      contents became smaller at more advanced stages, consistent with transition of
      material from the chorion to embryo tissue. Further, we determined the effect of
      2,4-dinitrophenol at a subacutely toxic concentration (14 MUM, LC10) as a model
      chemical challenge on the examined body mass related parameters. The compound
      caused significant decreases in phospholipid and glycolipid fatty acid contents
      along with a decrease in the phospholipid fatty acid unsaturation index. No major
      changes were observed for the other examined parameters. Lipidomic studies as
      performed here may thus be useful for determining subacute effects of lipophilic
      organic compounds on lipid metabolism and on cellular membranes of zebrafish
      embryos. 

PMID- 26292097
TI  - Repellent and Contact Toxicity of Alpinia officinarum Rhizome Extract against
      Lasioderma serricorne Adults.
AB  - The repellent and contact toxicities of Alpinia officinarum rhizome extract on
      Lasioderma serricorne adults, and its ability to protect stored wheat flour from
      L. serricorne adults infestation were investigated. The A. officinarum extract
      exhibited strong repellent and contact toxicities against L. serricorne adults.
      The toxicities enhanced significantly with the increasing treatment time and
      treatment dose. The mean percentage repellency value reached 91.3% at class V at
      the dose of 0.20 MUL/cm2 after 48 h of exposure. The corrected mortality reached
      over 80.0% at the dose of 0.16 MUL/cm2 after 48 h of exposure. The A. officinarum
      extract could significantly reduce L. serricorne infestation level against stored
      wheat flour. Particularly, the insect infestation was nil in wheat flour packaged
      with kraft paper bags coated with the A. officinarum extract at the dose of above
      0.05 MUL/cm2. The naturally occurring A. officinarum extract could be useful for
      integrated management of L. serricorne. 

PMID- 26292098
TI  - Reemergence and Autochthonous Transmission of Dengue Virus, Eastern China, 2014.
AB  - In 2014, 20 dengue cases were reported in the cities of Wenzhou (5 cases) and
      Wuhan (15 cases), China, where dengue has rarely been reported. Dengue virus 1
      was detected in 4 patients. Although most of these cases were likely imported,
      epidemiologic analysis provided evidence for autochthonous transmission. 

PMID- 26292101
TI  - Eutrophication potential of lakes: an integrated analysis of trophic state,
      morphometry, land occupation, and land use.
AB  - Despite being inside a protected area, Lake Sumidouro has been impacted by the
      anthropogenic occupation of the surrounding area since the 1970's, compromising
      the ecological integrity of the lake and the sustainable use of natural
      resources. This study examined the current trophic classification of the lake and
      developed methods for improving it through an integrated analysis of morphometric
      and limnological parameters, land use and land occupation in the watershed, and
      eutrophication potential. Data for the limnological parameters, land use and land
      occupation, and morphometric characteristics of Lake Sumidouro were collected in
      the rainy and dry seasons of 2009 and 2010. Depending on the trophic
      classification system used, Lake Sumidouro is classified as oligotrophic to
      hypereutrophic. In our study, the highest concentration of nutrients occurred in
      the rainy season, indicating that high nutrient inputs played an important role
      during this period. Areas of anthropogenic occupation comprised approximately
      62.9% of the total area of the watershed, with pasture and urban settlement as
      the main types of land use. The influent total phosphorus load was estimated to
      be 15,824.3 kg/year. To maintain mesotrophic conditions, this load must be
      reduced by 29.4%. By comparing the isolated use of trophic state indices, this
      study demonstrated that comparing the trophic state classification with
      morphometric analyses, land use and land occupation types in the watershed, and
      potential phosphorus load provided better information to guide management actions
      for restoration and conservation. Furthermore, this approach also allowed for
      evaluating the vulnerability of the environment to the eutrophication process. 

PMID- 26292099
TI  - Differential Host Immune Responses after Infection with Wild-Type or Lab
      Attenuated Rabies Viruses in Dogs.
AB  - METHODOLOGY/PRINCIPAL FINDINGS: The experimental infection of dogs with TriGAS
      induced high levels of VNA in the serum, whereas wt RABV infection did not. Dogs
      infected with TriGAS developed antibodies against the virus including its
      glycoprotein, whereas dogs infected with DRV-NG11 only developed rabies
      antibodies that are presumably specific for the nucleoprotein, (N) and not the
      glycoprotein (G). We show that infection with TriGAS induces early activation of
      B cells in the draining lymph nodes and persistent activation of DCs and B cells
      in the blood. On the other hand, infection with DRV-NG11 fails to induce the
      activation of DCs and B cells and further reduces CD4 T cell production. Further,
      we show that intrathecal (IT) immunization of TriGAS not only induced high levels
      of VNA in the serum but also in the CSF while intramuscular (IM) immunization of
      TriGAS induced VNA only in the serum. In addition, high levels of total protein
      and WBC were detected in the CSF of IT immunized dogs, indicating the transient
      enhancement of blood-brain barrier (BBB) permeability, which is relevant to the
      passage of immune effectors from periphery into the CNS.
      CONCLUSIONS/SIGNIFICANCE: IM infection of dogs with TriGAS induced the production
      of serum VNA whereas, IT immunization of TriGAS in dogs induces high levels of
      VNA in the periphery as well as in the CSF and transiently enhances BBB
      permeability. In contrast, infection with wt DRV-NG11 resulted in the production
      of RABV-reactive antibodies but VNA and antibodies specific for G were absent. As
      a consequence, all of the dogs infected with wt DRV-NG11 succumbed to rabies.
      Thus the failure to activate protective immunity is one of the important features
      of RABV pathogenesis in dogs.

PMID- 26292102
TI  - Invasion of the alien gecko Hemidactylus mabouia(Moureau de Jonnes, 1818) in a
      natural habitat at Praia do Sul Biological Reserve, Ilha Grande, RJ, Brazil.

PMID- 26292100
TI  - Prognostic value of (18) F-fluoroazomycin arabinoside PET/CT in patients with
      advanced non-small-cell lung cancer.
AB  - This study evaluated the prognostic value of positron emission
      tomography/computed tomography (PET/CT) using (18) F-fluoroazomycin arabinoside
      (FAZA) in patients with advanced non-small-cell lung cancer (NSCLC) compared with
      (18) F-fluorodeoxyglucose (FDG). Thirty-eight patients with advanced NSCLC (stage
      III, 23 patients; stage IV, 15 patients) underwent FAZA and FDG PET/CT before
      treatment. The PET parameters (tumor-to-muscle ratio [T/M] at 1 and 2 h for FAZA,
      maximum standardized uptake value for FDG) in the primary lesion and lymph node
      (LN) metastasis and clinical parameters were compared concerning their effects on
      progression-free survival (PFS) and overall survival (OS). In our univariate
      analysis of all patients, clinical stage and FAZA T/M in LNs at 1 and 2 h were
      predictive of PFS (P = 0.021, 0.028, and 0.002, respectively). Multivariate
      analysis also indicated that clinical stage and FAZA T/M in LNs at 1 and 2 h were
      independent predictors of PFS. Subgroup analysis of chemoradiotherapy-treated
      stage III patients revealed that only FAZA T/M in LNs at 2 h was predictive of
      PFS (P = 0.025). The FDG PET/CT parameters were not predictive of PFS. No
      parameter was a significant predictor of OS. In patients with advanced NSCLC,
      FAZA uptake in LNs, but not in primary lesions, was predictive of treatment
      outcome. These results suggest the importance of characterization of LN
      metastases in advanced NSCLC patients. 

PMID- 26292104
TI  - Cultivation of marine shrimp in biofloc technology (BFT) system under different
      water alkalinities.
AB  - The aim of this study was to evaluate the influence of different levels of
      alkalinity for the superintensive cultivation of marine shrimp Litopenaeus
      vannamei in biofloc system. A total of 12 experimental circular units of 1000L
      were used supplied with 850L water from a nursery, populated at a density of 165
      shrimps.m-3 and average weight of 5.6 g. The treatments, in triplicate, consisted
      in four levels of alkalinity in the water: 40, 80, 120 and 160 mg.L-1 of calcium
      carbonate. To correct the alkalinity was used calcium hydroxide (CaOH). It was
      observed a decrease in pH of the water in the treatments with lower alkalinity
      (p<0.05). The total suspended settleable solids were also lower in the treatment
      of low alkalinity. No significant difference was observed in other physico
      chemical and biological parameters in the water quality assessed, as well as the
      zootechnical parameters of cultivation between treatments (p>=0.05). The results
      of survival and growth rate of shrimps were considered suitable for the
      cultivation system used in the different treatments. The cultivation of marine
      shrimp Litopenaeus vannamei in biofloc at density of 165 shrimps.m-3 can be
      performed in waters with alkalinity between 40 and 160 mg.L-1 of CaCO3, without
      compromising the zootechnical indexes of cultivation. 

PMID- 26292105
TI  - Bird assemblage mist-netted in an Atlantic Forest area: a comparison between
      vertically-mobile and ground-level nets.
AB  - Mist nets may be opened at different heights in the forest, but they are seldom
      used over 3 m above the ground. We used two different methods to compare species
      richness, composition, and relative abundance and trophic structure of the bird
      assemblage at Ilha Grande (with a 290 birds standardization): conventional ground
      level nets (0-2.4 m height range) and elevated nets (0-17 m) with an adjustable
      height system (modified from Humphrey et al., 1968) that we call vertically
      mobile nets. There were significant differences in capture frequencies between
      methods for about 20% of the species (Chi-squared test, P<0.05), and the two
      methods caught different assemblages. Ground-level nets recorded less species,
      and they comparatively overestimated mainly Suboscine insectivores and
      underestimated frugivores and nectarivores. Different sampling methods used at
      the same location may result in very different diagnoses of the avifauna present,
      both qualitatively and quantitatively. We encourage studies involving mist net
      sampling to include the upper strata to more accurately represent the avifauna in
      Atlantic Forest. 

PMID- 26292106
TI  - Socioeconomic Disparities and Influenza Hospitalizations, Tennessee, USA.
AB  - We examined population-based surveillance data from the Tennessee Emerging
      Infections Program to determine whether neighborhood socioeconomic status was
      associated with influenza hospitalization rates. Hospitalization data collected
      during October 2007-April 2014 were geocoded (N = 1,743) and linked to
      neighborhood socioeconomic data. We calculated age-standardized annual incidence
      rates, relative index of inequality, and concentration curves for socioeconomic
      variables. Influenza hospitalizations increased with increased percentages of
      persons who lived in poverty, had female-headed households, lived in crowded
      households, and lived in population-dense areas. Influenza hospitalizations
      decreased with increased percentages of persons who were college educated, were
      employed, and had health insurance. Higher incidence of influenza hospitalization
      was also associated with lower neighborhood socioeconomic status when data were
      stratified by race. 

PMID- 26292107
TI  - Stereoselective Iterative Convergent Synthesis of Z-Oligodiacetylenes from
      Propargylic Dithioacetals.
AB  - A series of (t)Bu-substituted Z-oligodiacetylenes (Z-ODAs) are synthesized from
      the reactions of allenyl/propargylic zinc reagents, obtained from the
      corresponding propargylic dithiolanes and BuLi, with dithiolane-substituted
      propargylic aldehydes followed by stereospecific elimination of beta-thioalkoxy
      alcohols under Mitsunobu conditions. The stereochemical assignments are based on
      NOE experiments. The X-ray structure of the hexamer further supports the Z
      configuration for each of the double bonds in these ODAs. The photophysical
      properties of these Z-ODAs have been examined and are compared with known related
      E- and Z-ODAs with different substituents. 

PMID- 26292108
TI  - Fast Synthesis of Thiolated Au25 Nanoclusters via Protection-Deprotection Method.
AB  - This letter reports a new synthesis strategy for atomically precise Au
      nanoclusters (NCs) by using a protection-deprotection method. The key in our
      synthesis strategy is to introduce a surfactant molecule to protect thiolate
      Au(I) complexes during their reduction. The protecting layer provides a good
      steric hindrance and controls the formation rate of thiolated Au NCs, which leads
      to the direct formation of atomically precise Au NCs inside the protecting layer.
      The protecting layer was then removed from the surface of thiolated Au NCs to
      bring back the original functional groups on the NCs. The protection-deprotection
      method is simple and facile and can synthesize high-purity thiolated Au25 NCs
      within 10 min. Our synthesis protocol is fairly generic and can be easily
      extended to prepare Au25 NCs protected by other thiolate ligands. 

PMID- 26292110
TI  - Self-Assembly of Flux-Closure Polygons from Magnetite Nanocubes.
AB  - Well-defined nanoscale flux-closure polygons (nanogons) have been fabricated on
      hydrophilic surfaces from the face-to-face self-assembly of magnetite nanocubes.
      Uniform ferrimagnetic magnetite nanocubes (~86 nm) were synthesized and
      characterized with a combination of electron microscopy, diffraction, and
      magnetization measurements. The nanocubes were subsequently cast onto hydrophilic
      substrates, wherein the cubes lined up face-to-face and formed a variety of
      polygons due to magnetostatic and hydrophobic interactions. The generated
      surfaces consist primarily of three- and four-sided nanogons; polygons ranging
      from two to six sides were also observed. Further examination of the nanogons
      showed that the constraints of the face-to-face assembly of nanocubes often led
      to bowed sides, strained cube geometries, and mismatches at the acute angle
      vertices. Additionally, extra nanocubes were often present at the vertices,
      suggesting the presence of external magnetostatic fields at the polygon corners.
      These nanogons are inimitable nanoscale magnetic structures with potential
      applications in the areas of magnetic memory storage and high-frequency
      magnetics. 

PMID- 26292109
TI  - Why Is Cobalt the Best Transition Metal in Transition-Metal Hangman Corroles for
      O-O Bond Formation during Water Oxidation?
AB  - O-O bond formation catalyzed by a variety of beta-octafluoro hangman corrole
      metal complexes was investigated using density functional theory methods. Five
      transition metal elements, Co, Fe, Mn, Ru, and Ir, that are known to lead to
      water oxidation were examined. Our calculations clearly show that the formal
      Co(V) catalyst has a Co(IV)-corrole(*+) character and is the most efficient water
      oxidant among all eight transition-metal complexes. The O-O bond formation
      barriers were found to change in the following order: Co(V) ? Fe(V) < Mn(V) <
      Ir(V) < Co(IV) < Ru(V) < Ir(IV) < Mn(IV). The efficiency of water oxidation is
      discussed by analysis of the O-O bond formation step. Thus, the global trend is
      determined by the ability of the ligand d-block to accept two electrons from the
      nascent OH(-), as well as by the OH(*) affinity of the TM(IV)?O species of the
      corresponding TM(V)?O.H2O complex. Exchange-enhanced reactivity (EER) is
      responsible for the high catalytic activity of the Co(V) species in its S = 1
      state. 

PMID- 26292111
TI  - Graphene Oxide-Polythiophene Hybrid with Broad-Band Absorption and Photocatalytic
      Properties.
AB  - Hybrid graphene oxide (GO)/poly(3-hexylthiophene-2,5-diyl) (P3HT) sheets are
      assembled via pi-pi interaction and carefully isolated from the nonreacted
      precursors. The mutual influence of the two phases can be sharply manifested in
      this layer-to-layer configuration because it is undiluted by excess of one phase.
      To investigate the optical properties of the hybrid and possible synergistic
      interactions, we applied photothermal deflection spectroscopy (PDS) and pump
      probe techniques. For the first time, the photocatalytic performance of these
      hybrids was investigated to correlate with their optical properties. The GO-P3HT
      hybrid demonstrates broad-band absorption and ultrafast charge transfer (1.4 ps)
      and acts as an excellent photocatalyst for the Mannich reaction (93% yield). 

PMID- 26292112
TI  - Understanding Interfacial Electronic Structure and Charge Transfer: An
      Electrostatic Perspective.
AB  - The challenge of understanding electronic structure and dynamics at organic
      semiconductor interfaces arises from the richness and importance of weak
      interactions in thin films of extended pi-conjugated molecules. In this
      Perspective, I discuss a conceptually simple electrostatic approach toward a
      molecular-level description of the electronic structure and dynamics at a subset
      of such interfaces. Self-assembled monolayers of oriented dipolar molecules
      physisorbed on metal surfaces generate sizable collective electric fields, and
      electrostatics determines the key factors for energy level alignment and
      molecular electronic structure. A rigorous quantum mechanical treatment of such
      interfaces supports this conclusion and sheds light on the subtle interplay of
      the different interfacial interactions. The electrostatic model of the interface
      has the potential to offer also insights into the role of strong collective
      electric fields on interfacial charge-transfer dynamics. 

PMID- 26292113
TI  - Pyrite Nanocrystal Solar Cells: Promising, or Fool's Gold?
AB  - Pyrite-phase iron sulfide (FeS2) nanocrystals were synthesized to form solvent
      based dispersions, or "solar paint," to fabricate photovoltaic devices (PVs).
      Nanocrystals were sprayed onto substrates as absorber layers in devices with
      several different architectures, including Schottky barrier, heterojunction, and
      organic/inorganic hybrid architectures, to explore their viability as a PV
      material. None of the devices exhibited PV response. XRD and Raman spectroscopy
      confirmed the pyrite composition and phase purity of the nanocrystals. The
      electrical conductivity of the nanocrystal films was about 4 to 5 S/cm, more
      typical of metal nanocrystal films than semiconductor nanocrystal films, and the
      lack of PV response appears to derive from the highly conductive surface-related
      defects in pyrite that have been proposed. 

PMID- 26292114
TI  - Memory-Assisted Exciton Diffusion in the Chlorosome Light-Harvesting Antenna of
      Green Sulfur Bacteria.
AB  - Chlorosomes are likely the largest and most efficient natural light-harvesting
      photosynthetic antenna systems. They are composed of large numbers of
      bacteriochlorophylls organized into supramolecular aggregates. We explore the
      microscopic origin of the fast excitation energy transfer in the chlorosome using
      the recently resolved structure and atomistic-detail simulations. Despite the
      dynamical disorder effects on the electronic transitions of the
      bacteriochlorophylls, our simulations show that the exciton delocalizes over the
      entire aggregate in about 200 fs. The memory effects associated to the dynamical
      disorder assist the exciton diffusion through the aggregates and enhance the
      diffusion coefficients as a factor of 2 as compared to the model without memory.
      Furthermore, exciton diffusion in the chlorosome is found to be highly
      anisotropic with the preferential transfer toward the baseplate, which is the
      next functional element in the photosynthetic system. 

PMID- 26292115
TI  - Vibrational Dynamics of a Perylene-Perylenediimide Donor-Acceptor Dyad Probed
      with Femtosecond Stimulated Raman Spectroscopy.
AB  - The ultrafast vibrational dynamics of the photoinduced charge-transfer reaction
      between perylene (Per) and perylene-3,4:9,10-bis(dicarboximide) (PDI) were
      investigated using femtosecond stimulated Raman spectroscopy (FSRS). Specifically
      probing the structural dynamics of PDI following its selective photoexcitation in
      a covalently linked dyad reveals vibrational modes uniquely characteristic to the
      PDI lowest excited singlet state and radical anion between 1000 and 1700 cm(-1).
      A comparison of these vibrations to those of the ground state reveals the
      appearance of new (1*)PDI and PDI(-*) stretching modes in the dyad at 1593 and
      1588 cm(-1), respectively. DFT calculations reveal that these vibrations are
      parallel to the long axis of PDI and thus then may be integral to the charge
      separation reaction. The ability to differentiate excited state from radical
      anion vibrational modes allows the evaluation of the influence of specific modes
      on the charge transfer dynamics in donor-bridge-acceptor systems based on PDI
      molecular constructs. 

PMID- 26292116
TI  - Determination of Singlet Exciton Diffusion Length in Thin Evaporated C60 Films
      for Photovoltaics.
AB  - C60 is used as an electron acceptor in small molecule photovoltaic devices in
      combination with various electron donors. The transport of excitons, i.e., bound
      electron/hole pairs, is an important factor determining the efficiency of such
      devices. Here we investigate the exciton diffusion length in C60 with the
      electrodeless time-resolved microwave conductance (TRMC) technique. Bilayers of
      30 nm Zn-phthalocyanine with a C60 layer with variable thickness are prepared by
      physical vapor deposition. Analysis of the photoconductance with an exciton
      diffusion model yields a diffusion length of 7 nm, and the mobility of holes
      along Zn-Phthalocyanine stacks is close to 1 cm(2)/(V s). From analysis of the
      rise and decay of the TRMC transients, we attribute the photoconductance to
      diffusion and dissociation of singlet excitons rather than triplets. The energy
      transfer rate between C60 molecules exceeds 8 * 10(10) s(-1). Exciton diffusion
      cannot be described by the Forster model due to the close proximity of the
      molecules. 

PMID- 26292117
TI  - Tuning the Interfacial Electronic Structure at Organic Heterojunctions by
      Chemical Design.
AB  - Quantum-chemical techniques are applied to assess the electronic structure at
      donor/acceptor heterojunctions of interest for organic solar cells. We show that
      electrostatic effects at the interface of model 1D stacks profoundly modify the
      energy landscape explored by charge carriers in the photoconversion process and
      that these can be tuned by chemical design. When fullerene C60 molecules are used
      as acceptors and unsubstituted oligothiophenes or pentacene are used as donors,
      the uncompensated quadrupolar electric field at the interface provides the
      driving force for splitting of the charge-transfer states into free charges. This
      quadrupolar field can be either enhanced by switching from a C60 to a perylene
      tetracarboxylic-dianhydride (PTCDA) acceptor or suppressed by grafting electron
      withdrawing groups on the donor. 

PMID- 26292118
TI  - Photoactivatable Synthetic Dyes for Fluorescence Imaging at the Nanoscale.
AB  - The transition from conventional to photoactivatable fluorophores can bring the
      resolution of fluorescence images from the micrometer to the nanometer level.
      Indeed, fluorescence photoactivation can overcome the limitations that
      diffraction imposes on the resolution of optical microscopes. Specifically,
      distinct fluorophores positioned within the same subdiffraction volume can be
      resolved only if their emissions are activated independently at different
      intervals of time. Under these conditions, the sequential localization of
      multiple probes permits the reconstruction of images with a spatial resolution
      that is otherwise impossible to achieve with conventional fluorophores. The
      irreversible photolysis of protecting groups or the reversible transformations of
      photochromic compounds can be employed to control the emission of appropriate
      fluorescent chromophores and allow the implementation of these ingenious
      operating principles for superresolution imaging. Such molecular constructs
      enable the spatiotemporal control that is required to avoid diffraction and can
      become invaluable analytical tools for the optical visualization of biological
      specimens and nanostructured materials with unprecedented resolution. 

PMID- 26292119
TI  - Electrostatic View at the Interface.

PMID- 26292120
TI  - Effect of Tether Conductivity on the Efficiency of Photoisomerization of
      Azobenzene-Functionalized Molecules on Au{111}.
AB  - We establish the role of tether conductivity on the photoisomerization of
      azobenzene-functionalized molecules assembled as isolated single molecules in
      well-defined decanethiolate self-assembled monolayer matrices on Au{111}. We
      designed the molecules so as to tune the conductivity of the tethers that
      separate the functional moiety from the underlying Au substrate. By employing
      surface-enhanced Raman spectroscopy, time-course measurements of surfaces
      assembled with azobenzene functionalized with different tether conductivities
      were independently studied under constant UV light illumination. The decay
      constants from the analyses reveal that photoisomerization on the Au{111} surface
      is reduced when the conductivity of the tether is increased. Experimental results
      are compared with density functional theory calculations performed on single
      molecules attached to Au clusters. 

PMID- 26292121
TI  - Correlating the Polymorphism of Titanyl Phthalocyanine Thin Films with Solar Cell
      Performance.
AB  - The structure of titanyl phthalocyanine (TiOPc) thin films is correlated with
      photovoltaic properties of planar heterojunction solar cells by pairing different
      TiOPc polymorph donor layers with C60 as an acceptor. Solvent annealing and the
      insertion of two different templating layers, namely 1H,1H,2H,2H
      perfluorodecyltrichlorosilane (FDTS) and CuI, prove to be effective methods to
      control the TiOPc thin film structure. The crystal phase of TiOPc thin films was
      identified by combining X-ray reflectivity (XRR) measurements with spectroscopic
      techniques, including absorption and micro-Raman measurements. Implementation of
      a donor layer with an absorption spectrum extending into the near-infrared (NIR)
      led to solar cells with external quantum efficiencies (EQEs) above 27% from
      lambda = 600 - 890 nm, with the best device yielding a power conversion
      efficiency (PCE) of 2.6%. Our results highlight the need to understand the
      relationship between processing parameters and thin film structure, as these have
      important consequences on device performance. 

PMID- 26292122
TI  - Temperature Nonequilibration during Single-Bubble Sonoluminescence.
AB  - Single-bubble sonoluminescence (SBSL) spectra from liquids having low vapor
      pressures, especially mineral acids, are exceptionally rich. During SBSL from
      aqueous sulfuric acid containing dissolved neon, rovibronic emission spectra
      reveal vibrationally hot sulfur monoxide (SO; Tv = 2100 K) that is also
      rotationally cold (Tr = 290 K). In addition to SO, excited neon atom emission
      gives an estimated temperature, for neon, of several thousand Kelvin. This
      nonequilibrated temperature is consistent with dynamically constrained SO
      formation at the liquid-vapor interface of the collapsing bubble. Formation
      occurs via collisions of fast neon atoms (generated within the collapsing bubble)
      with liquid-phase molecular species in the interfacial region, thus allowing for
      a mechanistic understanding of the processes leading to light emission. 

PMID- 26292123
TI  - Nonplanar Perylene Diimides as Potential Alternatives to Fullerenes in Organic
      Solar Cells.
AB  - Perylene diimides (PDIs) are attractive alternatives to fullerenes as electron
      transporters because of their optoelectronic properties, durability, and ease of
      synthesis. Belying this promise, devices that utilize PDIs as electron acceptors
      have low efficiencies. The primary deficiency in such cells is the low short
      circuit current density (JSC), which is traceable to the crystallinity of PDIs.
      Therefore, disrupting the crystallinity without adversely impacting the charge
      transfer properties of PDIs is proposed as an important design principle. This
      has been achieved using a nonplanar perylene. In combination with a hole
      transporting polymer, a device efficiency of 2.77% has been achieved. A 10-fold
      increase in JSC is observed in comparison with a planar PDI, resulting in one of
      the highest JSC values for a solution processed device featuring a PDI. Indeed,
      this is one of the highest efficiencies for devices featuring a nonfullerene as
      the electron transporter. 

PMID- 26292124
TI  - Interaction of Oxygen and Water with the (100) Surface of Pyrite: Mechanism of
      Sulfur Oxidation.
AB  - We present a density-functional study of the adsorption and reactions of oxygen
      and water with the (100) surface of pyrite. We find that dissociative adsorption
      is energetically favorable for oxygen, forming ferryl-oxo, Fe(4+)?O(2-), species.
      These transform easily to ferric-hydroxy, Fe(3+)-OH(-), in the presence of
      coadsorbed water, and the latter fully covers the surface under room conditions.
      A mechanism for surface oxidation is identified, which involves successive
      reactions with molecular oxygen and water, and leads to the complete oxidation of
      a surface sulfur to SO4(2-). The crucial recurring process is the surface O(2-)
      and OH(-) species acting as proton acceptors for incoming water molecules. Using
      a recently proposed method, we examine the oxidation state changes of the surface
      ions and the electron flow during the adsorption and oxidation processes. The
      oxidation mechanism is consistent with isotopic labeling experiments, suggesting
      that the oxygens in SO4(2-) from gas-phase oxidation are derived from water. 

PMID- 26292125
TI  - Gas-Phase Neutral Binary Oxide Clusters: Distribution, Structure, and Reactivity
      toward CO.
AB  - Neutral binary (vanadium-cobalt) oxide clusters are generated and detected in the
      gas phase for the first time. Their reactivities toward carbon monoxide (CO) are
      studied both experimentally and theoretically. Experimental results suggest that
      neutral VCoO4 can react with CO to generate VCoO3 and CO2. Density functional
      theory studies show parallel results as well as provide detailed reaction
      mechanisms. 

PMID- 26292126
TI  - Observation of Extremely High Vibrational Excitation in O2 from Inelastic
      Scattering of Rydberg H Atom with O2.
AB  - The state-resolved differential cross sections for the Rydberg-atom (RA)
      inelastic scattering process H*(n = 46) + O2(v = 0, j = 1,3) -> H*(n') + O2(v',
      j') have been measured by using the H-atom Rydberg tagging time-of-flight (HRTOF)
      technique. Extensive vibrational excitation of O2 products has been observed at
      the two collision energies of 0.64 and 1.55 eV. Experimental results show that
      the O2 products in the low vibrationally excited states are clearly forward
      scattered, whereas those in the highly vibrationally excited states are mainly
      backward-scattered. Partially resolved rotational structures were also observed
      and assigned. The striking observation of extremely high energy transfer from
      translational to vibrational excitation at the backward direction could be
      explained involving charge transfer between proton and O2 molecule and possibly
      complex formation during the scattering process. 

PMID- 26292127
TI  - Liquid Crystallinity and Dimensions of Surfactant-Stabilized Sheets of Reduced
      Graphene Oxide.
AB  - Graphene oxide (GO) flakes dissolved in water can spontaneously form liquid
      crystals. Liquid crystallinity presents an opportunity to process graphene
      materials into macroscopic assemblies with long-range ordering, but most graphene
      electronic functionalities are lost in oxidation treatments. Reduction of GO
      allows recovering functionalities and makes reduced graphene oxide (RGO) of
      greater interest. Unfortunately, chemical reduction of GO generally results in
      the aggregation of the flakes, with no liquid crystallinity observed. We report
      in the present work liquid crystals made of RGO. The addition of surfactants in
      appropriate conditions is used to stabilize the RGO flakes against aggregation
      maintaining their ability to form water-based liquid crystals. Structural and
      thermodynamical studies allow the dimensions of the flakes to be deduced. It is
      found that the thickness and diameter of RGO flakes are close to that of neat GO
      flakes. 

PMID- 26292128
TI  - Heterogeneous Structure, Heterogeneous Dynamics, and Complex Behavior in Two
      Dimensional Liquids.
AB  - Analysis of the metrical and topological features of the local structure in a
      freezing two-dimensional Lennard-Jones system found that in a narrow strip
      [Formula: see text] of thermodynamic states close to the melting line, the liquid
      becomes a complex liquid characterized by a super-Arrhenius increase of
      relaxation times, stretched-exponential decay of correlations in time, and a
      power-law distribution of waiting times for changes in the local order. In
      [Formula: see text], the structure of the liquid and its dynamics are spatially
      heterogeneous; the sizes of ordered clusters are power-law distributed. Those
      features are governed by local structure evolution between solid-like and liquid
      like (disordered) patterns. The liquid inside the strip [Formula: see text] gives
      a unique opportunity to study how heterogeneous structure, dynamics and
      complexity are intertwined with each other on a microscopic level. 

PMID- 26292129
TI  - Design Rules for High-Efficiency Quantum-Dot-Sensitized Solar Cells: A Multilayer
      Approach.
AB  - The effect of multilayer sensitization in quantum-dot (QD)-sensitized solar cells
      is reported. A series of electrodes, consisting of multilayer CdSe QDs were
      assembled on a compact TiO2 layer. Photocurrent measurements along with internal
      quantum efficiency calculation reveal similar electron collection efficiency up
      to a 100 nm thickness of the QD layers. Moreover, the optical density and the
      internal quantum efficiency measurements reveal that the desired surface area of
      the TiO2 electrode should be increased only by a factor of 17 compared with a
      compact electrode. We show that the sensitization of low-surface-area TiO2
      electrode with QD layers increases the performance of the solar cell, resulting
      in 3.86% efficiency. These results demonstrate a conceptual difference between
      the QD-sensitized solar cell and the dye-based system in which dye multilayer
      decreases the cell performance. The utilization of multilayer QDs opens new
      opportunities for a significant improvement of quantum-dot-sensitized solar cells
      via innovative cell design. 

PMID- 26292130
TI  - Electron and Hole Contributions to the Terahertz Photoconductivity of a
      Conjugated Polymer:Fullerene Blend Identified.
AB  - Time-resolved terahertz spectroscopy was employed for the investigation of charge
      transport dynamics in benzothiadiazolo-dithiophene polyfluorene ([2,7-(9,9
      dioctyl-fluorene)-alt-5,5-(4',7'-di-2-thienyl-2',1',3'-benzothiadiazole)]) (APFO
      3) polymers with various chain lengths and in its monomer form, all blended with
      an electron acceptor ([6,6]-phenyl-C61-butyric acid methyl ester, PCBM). Upon
      photoexcitation, charged polaron pairs are created, negative charges are
      transferred to fullerenes, while positive polarons remain on polymers/monomers.
      Vastly different hole mobility in polymer and monomer blends allows us to
      distinguish the hole and electron contributions to the carrier mobility. 

PMID- 26292131
TI  - Viscosity and Wetting Property of Water Confined in Extended Nanospace
      Simultaneously Measured from Highly-Pressurized Meniscus Motion.
AB  - Understanding fluid and interfacial properties in extended nanospace (10-1000 nm)
      is important for recent advances of nanofluidics. We studied properties of water
      confined in fused-silica nanochannels of 50-1500 nm sizes with two types of cross
      section: (1) square channel of nanoscale width and depth, and (2) plate channel
      of microscale width and nanoscale depth. Viscosity and wetting property were
      simultaneously measured from capillary filling controlled by megapascal external
      pressure. The viscosity increased in extended nanospace, while the wetting
      property was almost constant. Especially, water in the square nanochannels had
      much higher viscosity than the plate channel, which can be explained considering
      loosely coupled water molecules by hydrogen bond on the surface within 24 nm.
      This study suggests specificity of fluids two-dimensionally confined in extended
      nanoscale, in which the liquid is highly viscous by the specific water phase,
      while the wetting dynamics is governed by the well-known adsorbed water layer of
      several-molecules thickness. 

PMID- 26292132
TI  - Competition between Ultrafast Energy Flow and Electron Transfer in a Ru(II)
      Loaded Polyfluorene Light-Harvesting Polymer.
AB  - This Letter describes the synthesis and photophysical characterization of a
      Ru(II) assembly consisting of metal polypyridyl complexes linked together by a
      polyfluorene scaffold. Unlike many scaffolds incorporating saturated linkages,
      the conjugated polymer in this system acts as a functional light-harvesting
      component. Conformational disorder breaks the conjugation in the polymer
      backbone, resulting in a chain composed of many chromophore units, whose relative
      energies depend on the segment lengths. Photoexcitation of the polyfluorene by a
      femtosecond laser pulse results in the excitation of polyfluorene, which then
      undergoes direct energy transfer to the pendant Ru(II) complexes, producing
      Ru(II)* excited states within 500 fs after photoexcitation. Femtosecond transient
      absorption data show the presence of electron transfer from PF* to Ru(II) to form
      charge-separated (CS) products within 1-2 ps. The decay of the oxidized and
      reduced products, PF(+*) and Ru(I), through back electron transfer are followed
      using picosecond transient absorption methods. 

PMID- 26292133
TI  - Solvation Stokes-Shift Dynamics Studied by Chirped Femtosecond Laser Pulses.
AB  - The early optical dynamic response, resulting population, and electronic
      coherence are investigated experimentally and modeled theoretically for IR144 in
      solution. The fluorescence and stimulated emission response are studied
      systematically as a function of chirp. The magnitude of the chirp effect on
      fluorescence and stimulated emission is found to depend quadratically on pulse
      energy, even where excitation probabilities range from 0.02 to 5%, in the so
      called "linear excitation regime". Interestingly, the shape of the chirp
      dependence on fluorescence and stimulated emission is found to be independent of
      pulse energy. The chirp dependence reveals dynamics related to solvent
      rearrangement following excitation and also depends on electronic relaxation of
      the chromophore. The experimental results are successfully simulated using a four
      level model in the presence of inhomogeneous broadening of the electronic
      transitions. 

PMID- 26292134
TI  - Molecular Dynamics Simulation Study of the Capacitive Performance of a Binary
      Mixture of Ionic Liquids near an Onion-like Carbon Electrode.
AB  - An equimolar mixture of 1-methyl-1-propylpyrrolidinium
      bis(trifluoromethylsulfonyl)imide ([C3mpy][Tf2N]), 1-methyl-1-butylpiperidinium
      bis(trifluoromethylsulfonyl)imide ([C4mpip][Tf2N]) was investigated by classic
      molecular dynamics (MD) simulation. Differential scanning calorimetry (DSC)
      measurements verified that the binary mixture exhibited lower glass transition
      temperature than either of the pure room-temperature ionic liquids (RTILs).
      Moreover, the binary mixture gave rise to higher conductivity than the neat RTILs
      at lower temperature range. In order to study its capacitive performance in
      supercapacitors, simulations were performed of the mixture, and the neat RTILs
      used as electrolytes near an onion-like carbon (OLC) electrode at varying
      temperatures. The differential capacitance exhibited independence of the
      electrical potential applied for three electrolytes, which is in agreement with
      previous work on OLC electrodes in a different RTILs. Positive temperature
      dependence of the differential capacitance was observed, and it was dominated by
      the electrical double layer (EDL) thickness, which is for the first time
      substantiated in MD simulation. 

PMID- 26292135
TI  - Importance of Correctly Describing Charge-Transfer Excitations for Understanding
      the Chemical Effect in SERS.
AB  - The enhancement mechanism due to the molecule-surface chemical coupling in
      surface-enhanced Raman scattering (SERS) is governed to a large extent by the
      energy difference between the highest occupied molecular orbital (HOMO) of the
      metal and the lowest unoccupied molecular orbital (LUMO) of the molecule. Here,
      we investigate the importance of correctly describing charge-transfer
      excitations, using time-dependent density functional theory (TDDFT), when
      calculating the chemical coupling in SERS. It is well-known that TDDFT, using
      traditional functionals, underestimates the position of charge-transfer
      excitations. Here, we show that this leads to a significant overestimation of the
      chemical coupling mechanism in SERS. Significantly smaller enhancements are found
      using long-range corrected (LC) functionals as compared with a traditional
      generalized gradient approximation (GGA) and hybrid functionals. Enhancement
      factors are found to be smaller than 530 and typically less than 50. Our results
      show that it is essential to correctly describe charge-transfer excitations for
      predicting the chemical enhancement in SERS. 

PMID- 26292136
TI  - Electrochemical Characterization of Water-Soluble Au25 Nanoclusters Enabled by
      Phase-Transfer Reaction.
AB  - We report the synthesis and electrochemical characterization of a new water
      soluble Au25 cluster protected with (3-mercaptopropyl)sulfonate. The presence of
      sulfonate terminal groups on the surface of the cluster enabled facile phase
      transfer of the water-soluble cluster to organic phase by ion-pairing with
      hydrophobic counterions. The phase-transferred form of the water-soluble Au25
      cluster was found to retain its integrity and allowed investigation of its
      electrochemical properties in organic media. The voltammetric investigation of
      the phase-transferred Au25 cluster in mixtures of CH2Cl2 and toluene has revealed
      that the cluster exhibits the characteristic Au25 peak pattern, but the
      electrochemical HOMO-LUMO energy gap of the cluster varies from 1.39 to 1.66 V
      depending on the solvent polarity. The origin of the solvent dependence is
      explained by the electrostatic field effect of the sulfonate anion on the redox
      potentials of the Au25 cluster. 

PMID- 26292137
TI  - Quantum Dynamics of the HO + CO -> H + CO2 Reaction on an Accurate Potential
      Energy Surface.
AB  - Full-dimensional quantum dynamics of the HO + CO -> H + CO2 reaction is
      investigated on a recent global potential energy surface based on a large number
      of ab initio points. The J = 0 reaction probability is small and essentially a
      monotonically increasing function with energy, superimposed by overlapping
      resonances. The reactivity is considerably enhanced by OH vibrational excitation
      while relatively insensitive to CO vibrational excitation. The rate constant
      estimated by the J-shifting approximation indicates a much better agreement with
      experiment than that obtained on a previous potential energy surface. 

PMID- 26292138
TI  - Determination of Excited-State Energies and Dynamics in the B Band of the
      Bacterial Reaction Center with 2D Electronic Spectroscopy.
AB  - Photosynthetic organisms convert photoenergy to chemical energy with near-unity
      quantum efficiency. This occurs through charge transfer in the reaction center,
      which consists of two branches of pigments. In bacteria, both branches are energy
      transfer pathways, but only one is also an electron transfer pathway. One barrier
      to a full understanding of the asymmetry is that the two branches contain excited
      states close in energy that produce overlapping spectroscopic peaks. We apply
      polarization-dependent, 2D electronic spectroscopy to the B band of the oxidized
      bacterial reaction center. The spectra reveal two previously unresolved peaks,
      corresponding to excited states localized on each of the two branches.
      Furthermore, a previously unknown interaction between these two states is
      observed on a time scale of ~100 fs. This may indicate an alternative pathway to
      electron transfer for the oxidized reaction center and thus may be a mechanism to
      prevent energy from becoming trapped in local minima. 

PMID- 26292139
TI  - Realizing Visible Photoactivity of Metal Nanoparticles: Excited-State Behavior
      and Electron-Transfer Properties of Silver (Ag8) Clusters.
AB  - Silver nanoclusters complexed with dihydrolipoic acid (DHLA) exhibit molecular
      like excited-state properties with well-defined absorption and emission features.
      The 1.8 nm diameter Ag nanoparticles capped with Ag8 clusters exhibit
      fluorescence maximum at 660 nm with a quantum yield of 0.07%. Although the
      excited state is relatively short-lived (tau 130 ps), it exhibits significant
      photochemical reactivity. By introducing MV(2+) as a probe, we have succeeded in
      elucidating the interfacial electron transfer dynamics of Ag nanoclusters. The
      formation of MV(+*) as the electron-transfer product with a rate constant of 2.74
      * 10(10) s(-1) confirms the ability of these metal clusters to participate in the
      photocatalytic reduction process. Basic understanding of excited-state processes
      in fluorescent metal clusters paves the way toward the development of biological
      probes, sensors, and catalysts in energy conversion devices. 

PMID- 26292140
TI  - How a Quantum Chemical Topology Analysis Enables Prediction of Electron Density
      Transfers in Chemical Reactions. The Degenerated Cope Rearrangement of
      Semibullvalene.
AB  - Recent works on the reaction mechanism for the degenerated Cope rearrangement
      (DCR) of semibullvalene (SBV) in the ground state prompted us to investigate this
      complex rearrangement in order to assign experimentally observed contrast
      features in the simulated electron distribution. We present a joint use of the
      electron localization function (ELF) and Thom's catastrophe theory (CT) as a
      powerful tool to analyze the electron density transfers along the DCR. The
      progress of the reaction is monitored by the structural stability domains of the
      topology of ELF, while the change between them is controlled by turning points
      derived from CT. The ELF topological analysis shows that the DCR of SBV
      corresponds to asynchronous electron density rearrangement taking place in three
      consecutive stages. We show how the pictures anticipated by drawing Lewis
      structures of the rearrangement correlate with the experimental data and time
      dependent quantum description of the process. 

PMID- 26292141
TI  - An Extended Charge Equilibration Method.
AB  - We present a method for estimating partial atomic charges that uses all of the
      measured ionization energies (first, second, third, etc.) for every atom in the
      periodic table. We build on the charge equilibration (Qeq) method of Rappe and
      Goddard (which used only the first ionization energies) but reduce the number of
      ad hoc parameters from at least one for every type of atom to just two global
      parameters: a dielectric strength and a modified parameter for hydrogen atoms.
      Periodic electrostatic interactions are calculated via Ewald sums, and the
      partial charges are determined by simultaneously solving a system of linear
      equations; no iteration is required. We compare the predicted partial atomic
      charges of this extended charge equilibration (EQeq) scheme against plane-wave
      density-functional theory derived charges determined via the REPEAT method for 12
      diverse metal-organic frameworks (MOFs). We also compare EQeq charges against
      ChelpG charges calculated using nonperiodic MOF fragments, as well as against Qeq
      charges as implemented in Accelrys Materials Studio. We demonstrate that for the
      purpose of ranking MOFs from best to worst for carbon capture applications, EQeq
      charges perform as well as charges derived from electrostatic potentials, but
      EQeq requires only a tiny fraction of the computational cost (seconds vs days for
      the MOFs studied). The source code for the EQeq algorithm is provided. 

PMID- 26292142
TI  - Tunable Ether Production via Coupling of Aldehydes or Aldehyde/Alcohol over
      Hydrogen-Modified Gold Catalysts at Low Temperatures.
AB  - Ethers are an important group of organic compounds that are primarily prepared
      via homogeneous catalysis, which can lead to operational and environmental
      issues. Here we demonstrate the production of ethers via heterogeneous catalysis
      over H adatom-covered gold at temperatures lower than 250 K. Symmetrical ethers
      can be formed via a self-coupling reaction of corresponding aldehydes; for
      example, homocoupling of acetaldehyde and propionaldehyde yields diethyl ether
      and di-n-propyl ether, respectively. In addition, coupling reactions between
      alcohols and aldehydes, with different carbon chain lengths, are observed via the
      production of the corresponding unsymmetrical ethers. A reaction mechanism is
      proposed, suggesting that an alcohol-like intermediate via partial hydrogenation
      of aldehydes on the surface plays a key role in these reactions. These surface
      chemical reactions suggest possible heterogeneous routes to low-temperature
      production of ethers. 

PMID- 26292143
TI  - Equivalent Circuit of Electrons and Holes in Thin Semiconductor Films for
      Photoelectrochemical Water Splitting Applications.
AB  - A simple model for the kinetics of electrons and holes in a thin semiconductor
      film in photoelectrochemical water splitting conditions is discussed, with a
      focus to discriminate between trap-assisted recombination and charge-transfer
      processes. We formulate the kinetic model in terms of the measurements of
      impedance spectroscopy and discuss the application of the results for the
      interpretation of the current potential curve under photogeneration. We provide a
      rigorous structure of the fundamental equivalent circuit for photoelectrochemical
      water splitting systems including a new predicted feature that is a chemical
      capacitance of the minority carriers that can give rise, in combination with
      other standard features, to a total of three arcs in the complex plane. 

PMID- 26292144
TI  - Activation of Metal-Organic Precursors by Electron Bombardment in the Gas Phase
      for Enhanced Deposition of Solid Films.
AB  - The incorporation of gas-phase electron-impact ionization and activation of metal
      organic compounds into atomic layer deposition (ALD) processes is reported as a
      way to enhance film growth with stable precursors. Specifically, it is shown here
      that gas-phase activation of methylcyclopentadienylmanganese tricarbonyl,
      MeCpMn(CO)3, which was accomplished by using a typical nude ion gauge employed in
      many ultrahigh-vacuum (UHV) studies, enhances its dissociative adsorption on
      silicon surfaces, affording the design of ALD cycles with more extensive Mn
      deposition and at lower temperatures. Significantly higher Mn uptakes were
      demonstrated by X-ray photoelectron spectroscopy (XPS) on both silicon dioxide
      films and on Si(100) wafers Ar(+)-sputtered to remove their native oxide layer.
      The effectiveness of this electron-impact activation approach in ALD is explained
      in terms of the cracking patterns seen in mass spectrometry for the metal-organic
      precursor used. 

PMID- 26292145
TI  - When will is not the same as should: The role of modals in reasoning with legal
      conditionals.
AB  - Naive reasoners reject logically valid conclusions from conditional rules if they
      can think of exceptions in which the antecedent is true, but the consequent is
      not. However, when reasoning with legal conditionals (e.g., "If a person kills
      another human, then this person should be punished for manslaughter") people
      hardly consider exceptions but evaluate conclusions depending on their own sense
      of justice. We show that participants' reluctance to consider exceptions in legal
      reasoning depends on the modal auxiliary used. In two experiments we phrased
      legal conditionals either with the modal "should" (i.e., " . . . then this person
      should be punished"), or with "will" (i.e., " . . . then this person will be
      punished") and presented them as modus ponens or modus tollens inferences.
      Participants had to decide whether the offender should or will be punished (modus
      ponens) or whether the offender indeed committed the offence (modus tollens). For
      modus ponens inferences phrased with "should" we replicate previous findings
      showing that participants select conclusions on the basis of their own sense of
      justice (Experiments 1 and 2). Yet, when the legal conditional is phrased with
      the modal "will" this effect is attenuated (Experiments 1 and 2), and exceptions
      are considered (Experiment 1). The modal auxiliary did not affect modus tollens
      inferences.

PMID- 26292146
TI  - Pulmonary Venous Varix.

PMID- 26292147
TI  - Nanoplasmonic imaging of latent fingerprints with explosive RDX residues.
AB  - Explosive detection is a critical element in preventing terrorist attacks,
      especially in crowded and influential areas. It is probably more important to
      establish the connection of explosive loading with a carrier's personal identity.
      In the present work, we introduce fingerprinting as physical personal
      identification and develop a nondestructive nanoplasmonic method for the imaging
      of latent fingerprints. We further integrate the nanoplasmonic response of
      catalytic growth of Au NPs with NADH-mediated reduction of 1,3,5-trinitro-1,3,5
      triazinane (RDX) for the quantitative analysis of RDX explosive residues in
      latent fingerprints. This generic nanoplasmonic strategy is expected to be used
      in forensic investigation to distinguish terrorists that carry explosives. 

PMID- 26292148
TI  - Insertion of Trivalent Lanthanides into Uranyl Vanadate Layers and Frameworks.
AB  - Two new uranyl vanadates have been prepared from hydrothermal reactions and
      structurally characterized by single-crystal X-ray diffraction. The structure of
      (H3O)UO2VO4 (UVO-1) consists of anionic layers containing UO2(2+) pentagonal
      bipyramids coordinated by edge-sharing VO5 square pyramids, with the charge
      balanced by interlaminar H3O(+) cations. Vanadium in (UO2)3(VO4)2(H2O)3 (UVO-2)
      exists as monomeric VO4 tetrahedra coordinating to UO2(2+) pentagonal bipyramids,
      forming a 3D uranyl(VI) vanadate framework. Similar reactions with the addition
      of Ln(NO3)3 (Ln = Nd, Eu) afford the three heterobimetallic lanthanide uranyl
      vanadate frameworks Nd(UO2)3(VO4)3(H2O)11 (NdUVO-1), Eu(UO2)3(VO4)3(H2O)10 (EuUVO
      1), and Eu2(UO2)12(VO4)10(H2O)24 (EuUVO-2). In NdUVO-1 and EuUVO-1, Ln(3+)
      cations are inserted into the interlayer space of UVO-1 substituting for H3O(+)
      and further bridging adjacent layers into 3D frameworks. Similarly, EuUVO-2
      adopts the same sheet topology as UVO-2, with Eu(3+) ions replacing some of the
      interlayer uranyl ions in UVO-2. Our work has demonstrated that uranyl vanadate
      extended structures are excellent hosts for further incorporation of trivalent
      lanthanide/actinide cations and has provided a new way to create new
      heterobimetallic 4f-5f and 5f-5f compounds. 

PMID- 26292149
TI  - Evolutionary significance of ageing in the wild.
AB  - Human lifespan has risen dramatically over the last 150 years, leading to a
      significant increase in the fraction of aged people in the population. Until
      recently it was believed that this contrasted strongly with the situation in wild
      populations of animals, where the likelihood of encountering demonstrably
      senescent individuals was believed to be negligible. Over the recent years,
      however, a series of field studies has appeared that shows ageing can also be
      observed for many species in the wild. We discuss here the relevance of this
      finding for the different evolutionary theories of ageing, since it has been
      claimed that ageing in the wild is incompatible with the so-called non-adaptive
      (non-programmed) theories, i.e. those in which ageing is presumed not to offer a
      direct selection benefit. We show that a certain proportion of aged individuals
      in the population is fully compatible with the antagonistic pleiotropy and the
      disposable soma theories, while it is difficult to reconcile with the mutation
      accumulation theory. We also quantify the costs of ageing using life history data
      from recent field studies and a range of possible metrics. We discuss the merits
      and problems of the different metrics and also introduce a new metric, yearly
      death toll, that aims directly at quantifying the deaths caused by the ageing
      process.

PMID- 26292151
TI  - Cu-based carbene involved in a radical process: a new crossover reaction to
      construct gamma-peroxy esters and 1,4-dicarbonyl compounds.
AB  - Through merging Cu-based carbenes in a radical process, a novel crossover
      reaction has been successfully established, leading to the facile and efficient
      syntheses of various gamma-peroxy esters and 1,4-dicarbonyl compounds.
      Considering that both Cu-based carbene complexes and radicals are extremely
      reactive, and therefore exist only in extraordinarily low concentrations, the
      high selectivity of this coupling reaction is unusual. 

PMID- 26292150
TI  - Multiple Comparisons of Glucokinase Activation Mechanisms of Five Mulberry
      Bioactive Ingredients in Hepatocyte.
AB  - Glucokinase (GK) activity, which is rapidly regulated by glucokinase regulatory
      protein (GKRP) in the liver, is crucial for blood glucose homeostasis. In this
      paper, the GK activation mechanisms of 1-deoxynojrimycin (DNJ), resveratrol
      (RES), oxyresveratrol (OXY), cyanidin-3-glucoside (C3G), and cyanidin-3
      rutinoside (C3R) were compared. The results revealed that DNJ, RES, C3G, and C3R
      could differently improve glucose consumption and enhance intracellular GK
      activities. DNJ and RES significantly promoted GK translocation at 12.5 MUM,
      whereas other ingredients showed moderate effects. DNJ, C3G, and C3R could
      rupture intramolecular hydrogen bonds of GK to accelerate its allosteric
      activation at early stage. RES and OXY could bind to a "hydrophobic pocket" on GK
      to stabilize the active GK at the final stage. Otherwise, RES, OXY, C3G, and C3R
      could interact with GKRP at the F1P binding site to promote GK dissociation and
      translocation. Enzymatic assay showed that RES (15-50 MUM) and OXY (25-50 MUM)
      could significantly enhance GK activities, which was caused by their binding
      properties with GK. Moreover, the most dramatic up-regulation effects on GK
      expression were observed in C3G and C3R groups. This work expounded the
      differences between GK activation mechanisms, and the new findings would help to
      develop new GK activators. 

PMID- 26292152
TI  - Flavors of EGFR-Ras signals impacting intestinal homeostasis.

PMID- 26292154
TI  - Antibody-drug conjugates: Intellectual property considerations.
AB  - Antibody-drug conjugates are highly complex entities that combine an antibody, a
      linker and a toxin. This complexity makes them demanding both technically and
      from a regulatory point of view, and difficult to deal with in their patent
      aspects. This article discusses different issues of patent protection and freedom
      to operate with regard to this promising new class of drugs. 

PMID- 26292155
TI  - Histomorphometry of the newly formed bone after its growth modulation by static
      and dynamic compression using a rat tail model.

PMID- 26292153
TI  - Impaired Cell Cycle Regulation in a Natural Equine Model of Asthma.
AB  - Recurrent airway obstruction (RAO) is a common and potentially debilitating lower
      airway disease in horses, which shares many similarities with human asthma. In
      susceptible horses RAO exacerbation is caused by environmental allergens and
      irritants present in hay dust. The objective of this study was the identification
      of genes and pathways involved in the pathology of RAO by global transcriptome
      analyses in stimulated peripheral blood mononuclear cells (PBMCs). We performed
      RNA-seq on PBMCs derived from 40 RAO affected and 45 control horses belonging to
      three cohorts of Warmblood horses: two half-sib families and one group of
      unrelated horses. PBMCs were stimulated with hay dust extract,
      lipopolysaccharides, a recombinant parasite antigen, or left unstimulated. The
      total dataset consisted of 561 individual samples. We detected significant
      differences in the expression profiles between RAO and control horses.
      Differential expression (DE) was most marked upon stimulation with hay dust
      extract. An important novel finding was a strong upregulation of CXCL13 together
      with many genes involved in cell cycle regulation in stimulated samples from RAO
      affected horses, in addition to changes in the expression of several HIF-1
      transcription factor target genes. The RAO condition alters systemic changes
      observed as differential expression profiles of PBMCs. Those changes also
      depended on the cohort and stimulation of the samples and were dominated by genes
      involved in immune cell trafficking, development, and cell cycle regulation. Our
      findings indicate an important role of CXCL13, likely macrophage or Th17 derived,
      and the cell cycle regulator CDC20 in the immune response in RAO. 

PMID- 26292156
TI  - Iodine deficiency in a study population of pregnant women in Sweden.
AB  - INTRODUCTION: Iodine deficiency in utero may impair neurological development of
      the fetus. In Sweden, iodine nutrition is considered to be adequate in the
      general population. The aim of this study was to evaluate iodine nutrition during
      pregnancy in Sweden. MATERIAL AND METHODS: In this cross-sectional study, the
      total study population (n = 459) consisted of two cohorts (Varmland County, n =
      273, and Uppsala County, n = 186) of pregnant non-smoking women without pre
      gestational diabetes mellitus or known thyroid disease before or during
      pregnancy. Spot urine samples were collected in the third trimester of pregnancy
      for median urinary iodine concentration (UIC) analysis. RESULTS: The median UIC
      in the total study population was 98 MUg/L (interquartile range 57-148 MUg/L).
      CONCLUSIONS: According to WHO/UNICEF/IGN criteria, population-based median UIC
      during pregnancy should be 150-249 MUg/L. Thus, our results indicate insufficient
      iodine status in the pregnant population of Sweden. There is an urgent need for
      further assessments in order to optimize iodine nutrition during pregnancy.

PMID- 26292157
TI  - How the cell got its mitochondria.

PMID- 26292158
TI  - Evolving Paradigms in Classification of Primary Angle Closure Glaucoma.
AB  - PURPOSE: To review the old and existing classification systems for primary angle
      closure disease. METHODS: Literature review and new proposed classification
      system. RESULTS: Existing classification systems have several shortcomings which
      cannot be applied in a clinical setting. This can be addressed by a proposed
      scoring system. CONCLUSION: A scoring system would be most appropriate for any
      clinical setting as well as for prognosticating primary angle closure disease.

PMID- 26292159
TI  - Multifunctional non-coding Epstein-Barr virus encoded RNAs (EBERs) contribute to
      viral pathogenesis.
AB  - Epstein-Barr Virus (EBV) is known as an oncogenic herpesvirus implicated in the
      pathogenesis of various malignancies. It has been reported that EBV non-coding
      RNAs (ncRNAs) including EBV-encoded small RNAs (EBERs) and EBV-miRNAs contribute
      to viral pathogenesis. EBERs that are expressed abundantly in latently EBV
      infected cells have been reported to play significant roles in tumorigenesis by
      EBV. Furthermore, it was demonstrated that the modulation of host innate immune
      signals by EBERs contributes to EBV-mediated pathogenesis including oncogenesis.
      Recently it was demonstrated that EBERs are secreted via exosomes by EBV-infected
      cells. It was also demonstrated that exosomes contain a number of EBV-encoded
      miRNAs. Various mRNAs have been identified as targets for regulation by EBV
      miRNAs in host cells, therefore, EBERs and EBV-miRNAs might function through the
      transfer of exosomes. 

PMID- 26292160
TI  - A Cervico-Thoraco-Lumbar Multibody Dynamic Model for the Estimation of Joint
      Loads and Muscle Forces.
AB  - Computational musculoskeletal models have been developed to predict mechanical
      joint loads on the human spine, such as the forces and moments applied to
      vertebral and facet joints and the forces that act on ligaments and muscles
      because of difficulties in the direct measurement of joint loads. However, many
      whole-spine models lack certain elements. For example, the detailed facet joints
      in the cervical region or the whole spine region may not be implemented. In this
      study, a detailed cervico-thoraco-lumbar multibody musculoskeletal model with all
      major ligaments, separated structures of facet contact and intervertebral disk
      joints, and the rib cage was developed. The model was validated by comparing the
      intersegmental rotations, ligament tensile forces, facet joint contact forces,
      compressive and shear forces on disks, and muscle forces were to those reported
      in previous experimental and computational studies both by region (cervical,
      thoracic, or lumbar regions) and for the whole model. The comparisons
      demonstrated that our whole spine model is consistent with in vitro and in vivo
      experimental studies and with computational studies. The model developed in this
      study can be used in further studies to better understand spine structures and
      injury mechanisms of spinal disorders. 

PMID- 26292161
TI  - Clinicopathologic features and prognostic indicators in Chinese patients with
      myelofibrosis.
AB  - OBJECTIVE: To define the clinicopathologic features, outcome, and prognostic
      indicators of myelofibrosis (MF) in Asian patients. METHODS: Two hundred and
      seventy consecutive Chinese patients (primary MF, n = 207; post-polycythemia vera
      MF, n = 27; and post-essential thrombocythemia MF, n = 36) from seven regional
      referral hospitals were analyzed. RESULTS: The median overall survival (OS) for
      primary MF was 66 months. Multivariate analysis showed that age >65 years (P =
      0.02), platelet count <100 * 10(9)/l (P = 0.001), and leukemic transformation (P
      = 0.001) negatively impacted on OS. The median OS of 63 patients with secondary
      MF was 44 months. In primary MF, the 10-year cumulative risk of leukemic
      transformation was 28%. On multivariate analysis, unfavorable karyotypes
      significantly predicted inferior leukemia-free survival (LFS) (P = 0.03). In
      secondary MF, the 10-year cumulative risk of leukemic transformation was 31%.
      Circulating blasts >=1% significantly predicted inferior LFS (P = 0.04). The
      international prognostic scoring system (IPSS) and dynamic IPSS were not
      significant survival predictors in our cohort. Eighteen patients underwent
      allogeneic hematopoietic stem cell transplantation. The median OS post
      transplantation was merely 19 months. DISCUSSION: Platelet count <100 * 10(9)/l,
      unfavorable karyotypes, and circulating blasts >1% were negative prognostic
      indicators. Conclusion Chinese MF patients were similar to Western patients in
      clinicopathologic features and outcome.

PMID- 26292162
TI  - A Review of Locomotion Systems for Capsule Endoscopy.
AB  - Wireless capsule endoscopy for gastrointestinal (GI) tract is a modern technology
      that has the potential to replace conventional endoscopy techniques. Capsule
      endoscopy is a pill-shaped device embedded with a camera, a coin battery, and a
      data transfer. Without a locomotion system, this capsule endoscopy can only
      passively travel inside the GI tract via natural peristalsis, thus causing
      several disadvantages such as inability to control and stop, and risk of capsule
      retention. Therefore, a locomotion system needs to be added to optimize the
      current capsule endoscopy. This review summarizes the state-of-the-art locomotion
      methods along with the desired locomotion features such as size, speed, power,
      and temperature and compares the properties of different methods. In addition,
      properties and motility mechanisms of the GI tract are described. The main
      purpose of this review is to understand the features of GI tract and diverse
      locomotion methods in order to create a future capsule endoscopy compatible with
      GI tract properties. 

PMID- 26292163
TI  - Factors Contributing to Recovery From Anesthesia and Postoperative Nausea and
      Vomiting.

PMID- 26292164
TI  - Anthropomorphic finger antagonistically actuated by SMA plates.
AB  - Most robotic applications that contain shape memory alloy (SMA) actuators use the
      SMA in a linear or spring shape. In contrast, a novel robotic finger was designed
      in this paper using SMA plates that were thermomechanically trained to take the
      shape of a flexed human finger when Joule heated. This flexor actuator was placed
      in parallel with an extensor actuator that was designed to straighten when Joule
      heated. Thus, alternately heating and cooling the flexor and extensor actuators
      caused the finger to flex and extend. Three different NiTi based SMA plates were
      evaluated for their ability to apply forces to a rigid and compliant object. The
      best of these three SMAs was able to apply a maximum fingertip force of 9.01N on
      average. A 3D CAD model of a human finger was used to create a solid model for
      the mold of the finger covering skin. Using a 3D printer, inner and outer molds
      were fabricated to house the actuators and a position sensor, which were
      assembled using a multi-stage casting process. Next, a nonlinear antagonistic
      controller was developed using an outer position control loop with two inner
      MOSFET current control loops. Sine and square wave tracking experiments
      demonstrated minimal errors within the operational bounds of the finger. The
      ability of the finger to recover from unexpected disturbances was also shown
      along with the frequency response up to 7 rad s(-1). The closed loop bandwidth of
      the system was 6.4 rad s(-1) when operated intermittently and 1.8 rad s(-1) when
      operated continuously. 

PMID- 26292165
TI  - Yeast diversity on grapes in two German wine growing regions.
AB  - The yeast diversity on wine grapes in Germany, one of the most northern wine
      growing regions of the world, was investigated by means of a culture dependent
      approach. All yeast isolates were identified by sequence analysis of the D1/D2
      domain of the 26S rDNA and the ITS region. Besides Hanseniaspora uvarum and
      Metschnikowia pulcherrima, which are well known to be abundant on grapes,
      Metschnikowia viticola, Rhodosporidium babjevae, and Curvibasidium
      pallidicorallinum, as well as two potentially new species related to
      Sporidiobolus pararoseus and Filobasidium floriforme, turned out to be typical
      members of the grape yeast community. We found M. viticola in about half of the
      grape samples in high abundance. Our data strongly suggest that M. viticola is
      one of the most important fermenting yeast species on grapes in the temperate
      climate of Germany. The frequent occurrence of Cu. pallidicorallinum and strains
      related to F. floriforme is a new finding. The current investigation provides
      information on the distribution of recently described yeast species, some of
      which are known from a very few strains up to now. Interestingly yeasts known for
      their role in the wine making process, such as Saccharomyces cerevisiae,
      Saccharomyces bayanus ssp. uvarum, Torulaspora delbrueckii, and Zygosaccharomyces
      bailii, were not found in the grape samples. 

PMID- 26292166
TI  - Multimodal probabilistic generative models for time-course gene expression data
      and Gene Ontology (GO) tags.
AB  - We propose four probabilistic generative models for simultaneously modeling gene
      expression levels and Gene Ontology (GO) tags. Unlike previous approaches for
      using GO tags, the joint modeling framework allows the two sources of information
      to complement and reinforce each other. We fit our models to three time-course
      datasets collected to study biological processes, specifically blood vessel
      growth (angiogenesis) and mitotic cell cycles. The proposed models result in a
      joint clustering of genes and GO annotations. Different models group genes based
      on GO tags and their behavior over the entire time-course, within biological
      stages, or even individual time points. We show how such models can be used for
      biological stage boundary estimation de novo. We also evaluate our models on
      biological stage prediction accuracy of held out samples. Our results suggest
      that the models usually perform better when GO tag information is included. 

PMID- 26292167
TI  - An information-theoretic approach to assess practical identifiability of
      parametric dynamical systems.
AB  - A new approach for assessing parameter identifiability of dynamical systems in a
      Bayesian setting is presented. The concept of Shannon entropy is employed to
      measure the inherent uncertainty in the parameters. The expected reduction in
      this uncertainty is seen as the amount of information one expects to gain about
      the parameters due to the availability of noisy measurements of the dynamical
      system. Such expected information gain is interpreted in terms of the variance of
      a hypothetical measurement device that can measure the parameters directly, and
      is related to practical identifiability of the parameters. If the individual
      parameters are unidentifiable, correlation between parameter combinations is
      assessed through conditional mutual information to determine which sets of
      parameters can be identified together. The information theoretic quantities of
      entropy and information are evaluated numerically through a combination of Monte
      Carlo and k-nearest neighbour methods in a non-parametric fashion. Unlike many
      methods to evaluate identifiability proposed in the literature, the proposed
      approach takes the measurement-noise into account and is not restricted to any
      particular noise-structure. Whilst computationally intensive for large dynamical
      systems, it is easily parallelisable and is non-intrusive as it does not
      necessitate re-writing of the numerical solvers of the dynamical system. The
      application of such an approach is presented for a variety of dynamical systems-
      ranging from systems governed by ordinary differential equations to partial
      differential equations--and, where possible, validated against results previously
      published in the literature.

PMID- 26292169
TI  - Spectroscopic evidence of 'jumping and pecking' of cholinium and H-bond enhanced
      cation-cation interaction in ionic liquids.
AB  - The subtle energy-balance between Coulomb-interaction, hydrogen bonding and
      dispersion forces governs the unique properties of ionic liquids. To measure weak
      interactions is still a challenge. This is in particular true in the condensed
      phase wherein a melange of different strong and directional types of interactions
      is present and cannot be detected separately. For the ionic liquids (2
      hydroxyethyl)-trimethylammonium (cholinium) bis(trifluoro-methylsulfonyl)amide
      and N,N,N-trimethyl-N-propylammonium bis(trifluoromethylsulfonyl)amide which
      differ only in the 2-hydroxyethyl and the propyl groups of the cations, we could
      directly observe distinct vibrational signatures of hydrogen bonding between the
      cation and the anion indicated by 'jumping and pecking' motions of cholinium. The
      assignment could be confirmed by isotopic substitution H/D at the hydroxyl group
      of cholinium. For the first time we could also find direct spectroscopic evidence
      for H-bonding between like-charged ions. The repulsive Coulomb interaction
      between the cations is overcome by cooperative hydrogen bonding between the 2
      hydroxyethyl functional groups of cholinium. This H-bond network is reflected in
      the properties of protic ionic liquids (PILs) such as viscosities and
      conductivities. 

PMID- 26292168
TI  - Selective detection of silver ions using mushroom-like polyaniline and gold
      nanoparticle nanocomposite-based electrochemical DNA sensor.
AB  - A highly sensitive electrochemical DNA biosensor made of polyaniline (PANI) and
      gold nanoparticles (AuNPs) nanocomposite (AuNPs@PANI) has been used for the
      detection of trace concentration of Ag(+). In the presence of Ag(+), with the
      interaction of cytosine-Ag(+)-cytosine (C-Ag(+)-C), cytosine-rich DNA sequence
      immobilized onto the surface of AuNPs@PANI has a self-hybridization and then
      forms a duplex-like structure. The whole detection procedure of Ag(+) based on
      the developed biosensor was evaluated by electrochemical impedance spectroscopy.
      On semi-logarithmic plots of the log Ag(+) concentration versus peak current, the
      results show that the prepared biosensor can detect silver ions at a wide linear
      range of 0.01-100 nM (R = 0.9828) with a detection limit of 10 pM (signal/noise =
      3). Moreover, the fabricated sensor exhibits good selectivity and repeatability.
      The detection of Ag(+) was determined by Ag(+) self-induced conformational change
      of DNA scaffold that involved only one oligonucleotide, showing its convenience
      and availability. 

PMID- 26292170
TI  - Biofilm formation and genetic diversity of Salmonella isolates recovered from
      clinical, food, poultry and environmental sources.
AB  - In the present study, Salmonella isolates (n=40) recovered from clinical, food,
      poultry and environmental sources were characterized for serotype identification,
      genetic diversity and biofilm formation capability. Serotype identification using
      multiplex PCR assay revealed six isolates to be Salmonella Typhimurium, 14 as
      Salmonella Enteritidis, 11 as Salmonella Typhi, and the remaining nine isolates
      unidentified were considered as other Salmonella spp. Most of the Salmonella
      isolates (85%) produced biofilm on polystyrene surfaces as assessed by microtitre
      plate assay. About 67.5% isolates were weak biofilm producers and 17.5% were
      moderate biofilm producers. There was no significant difference in biofilm
      forming ability among the Salmonella isolates recovered from different
      geographical regions or different sources. Among the genetic methods,
      Enterobacterial Repetitive Intergenic Consensus (ERIC) PCR revealed greater
      discriminatory power (DI, 0.943) followed by pulsed field gel electrophoresis
      (PFGE) (DI, 0.899) and random amplification of polymorphic DNA (RAPD) PCR (DI,
      0.873). However, composite analysis revealed the highest discrimination index
      (0.957). Greater discrimination of S. Typhimurium and S. Typhi was achieved using
      PFGE, while ERIC PCR was better for S. Enteritidis and other Salmonella
      serotypes. A strong positive correlation (r=0.992) was observed between biofilm
      formation trait and clustered Salmonella isolates in composite genetic analysis. 

PMID- 26292171
TI  - Mitogen-activated protein kinases and Hedgehog-GLI signaling in cancer: A
      crosstalk providing therapeutic opportunities?
AB  - The Hedgehog-GLI (HH-GLI) signaling is of critical importance during embryonic
      development, where it regulates a number of cellular processes, including
      patterning, proliferation and differentiation. Its aberrant activation has been
      linked to several types of cancer. HH-GLI signaling is triggered by binding of
      ligands to the transmembrane receptor patched and is subsequently mediated by
      transcriptional effectors belonging to the GLI family, whose function is fine
      tuned by a series of molecular interactions and modifications. Several HH-GLI
      inhibitors have been developed and are in clinical trials. Similarly, the mitogen
      activated protein kinases (MAPK) are involved in a number of biological processes
      and play an important role in many diseases including cancer. Inhibiting
      molecules targeting MAPK signaling, especially those elicited by the MEK1/2
      ERK1/2 pathway, have been developed and are moving into clinical trials. ERK1/2
      may be activated as a consequence of aberrant activation of upstream signaling
      molecules or during development of drug resistance following treatment with
      kinase inhibitors such as those for PI3K or BRAF. Evidence of a crosstalk between
      HH-GLI and other oncogenic signaling pathways has been reported in many tumor
      types, as shown by recent reviews. Here we will focus on the interaction between
      HH-GLI and the final MAPK effectors ERK1/2, p38 and JNK in cancer in view of its
      possible implications for cancer therapy. Several reports highlight the existence
      of a consistent crosstalk between HH signaling and MAPK, especially with the
      MEK1/2-ERK1/2 pathway, and this fact should be taken into consideration for
      designing optimal treatment and prevent tumor relapse. 

PMID- 26292172
TI  - Micronucleus frequency in peripheral blood lymphocytes and frailty status in
      elderly. A lack of association with clinical features.
AB  - Frailty is a condition of vulnerability that carries an increased risk of poor
      outcome in elder adults. Frail individuals show fatigue, weight loss, muscle
      weakness, and a reduced physical function, and are known to frequently experience
      disability, social isolation, and institutionalization. Identifying frail people
      is a critical step for geriatricians to provide timely geriatric care and,
      eventually, to improve the quality of life in elderly. The aim of the present
      study is to investigate the association between frailty status and micronucleus
      (MN) frequency, a known marker of genomic instability, in a sample of elder
      adults. Several clinical features were evaluated and their possible association
      with MN frequency was tested. Criteria proposed by Fried were used to identify
      frail subjects. Overall, 180 elder adults entered the study, 93 of them (51.7%)
      frail. No association between MN frequency and frailty status was found under the
      specific conditions tested in this study (mean ratio=1.06; 95% CI 0.96-1.18). The
      inclusion of MN frequency in the Fried's frailty scale minimally improved the
      classification of study subjects according to the multidimensional prognostic
      index (MPI). The presence of genomic instability in the ageing process and in
      most chronic diseases, demands further investigation on this issue. 

PMID- 26292173
TI  - A head-to-head comparison of the de Morton Mobility Index (DEMMI) and Elderly
      Mobility Scale (EMS) in an older acute medical population.
AB  - PURPOSE: To compare the clinimetric properties of the de Morton Mobility Index
      (DEMMI(r)) and the Elderly Mobility Scale (EMS). METHOD: A head-to-head
      comparison of the EMS and DEMMI(r) with 120 consecutive older acute medical
      patients. The DEMMI(r) and EMS were administered within 48 h of hospital
      admission and discharge. RESULTS: At admission, 6% and 15% of participants scored
      the lowest scale score for the DEMMI(r) and EMS, respectively. For the DEMMI(r),
      17% of participants scored within the minimal detectable change of the lowest
      scale score compared to 20% for the EMS at admission. At hospital discharge,
      DEMMI(r) scores were normally distributed and the EMS had a ceiling effect.
      Similar evidence of convergent, discriminant and known groups validity were
      obtained for the DEMMI(r) and EMS. There was no significant difference in
      responsiveness to change between the DEMMI(r) and EMS. The EMS was significantly
      quicker to administer compared to the DEMMI(r). CONCLUSION: The DEMMI(r) and EMS
      are both valid measures of mobility for older acute medical patients. The
      DEMMI(r) has a broader scale width than the EMS with interval level measurement
      and therefore provides a more accurate method for measuring and monitoring
      changes in mobility for older acute medical patients. Implications for
      Rehabilitation Mobility of older acute medical patients. Hospitalised older acute
      medical patients are at "high risk" of mobility decline. Accurate measurement of
      mobility is essential for preventing and treating mobility decline. Many existing
      mobility measures have significant measurement limitations. The DEMMI(r) is a
      more accurate measure of mobility than the EMS in an older acute medical
      population.

PMID- 26292174
TI  - Psychometric properties of the Spanish version of the Cumberland Ankle
      Instability Tool.
AB  - PURPOSE: To estimate the psychometric properties of the Spanish version of the
      Cumberland Ankle Instability Tool (CAIT-Sv). METHOD: One hundred and seventy-one
      subjects participated. The psychometric properties tested for CAIT-Sv were
      internal consistency with Cronbach's alpha (n = 171) in the first measurement;
      test-retest reliability using the intraclass correlation coefficient (ICC2,1) (n
      = 171) in two measurements separated by one week; criterion validity by ICC2,1
      between the original CAIT and CAIT-Sv in two measurements separated by two weeks
      for a subgroup of 54 bilingual subjects; ceiling and floor effects (n = 78
      subjects with a history of at least one ankle sprain), and responsiveness using
      Cohen's d in a subgroup of 25 subjects with a history of at least one ankle
      sprain and a score <=24 points on the CAIT-Sv and treated with a rehabilitation
      program during four weeks. RESULTS: Internal consistency was excellent
      (Cronbach's alpha: 0.8-0.84). Test-retest reliability was high (ICC2,1: 0.95).
      Criterion validity was high (ICC2,1: 0.91; 95% CI: 0.84-0.94; p < 0.001 for
      dominant ankle). There were no ceiling (9%) and floor (0%) effects.
      Responsiveness was moderate (Cohen's d: 0.6995; CI: 0.11-1.27). CONCLUSIONS: CAIT
      Sv is a reliable instrument with high criterion validity to measure the presence
      and severity of chronic ankle instability (CAI) in the Spanish population.
      Implications for Rehabilitation Chronic ankle instability is the most prevalent
      complication after ankle injuries. CAIT is a widely used tool for clinical
      detection of subjects with chronic ankle instability (CAI). In this study, CAIT
      Sv has shown good phsychometric properties for using with Spanish speaking
      individuals.

PMID- 26292175
TI  - Orthognathic Surgery in Patients With Congenital Myopathies and Congenital
      Muscular Dystrophies: Case Series and Review of the Literature.
AB  - PURPOSE: This case series examined preoperative findings and the surgical,
      anesthetic, and postoperative management of 6 patients with congenital myopathies
      (CMs) and congenital muscular dystrophies (CMDs) treated at a tertiary medical
      institution with orthognathic surgery over 15 years to describe pertinent
      considerations for performing orthognathic surgery in these complex patients.
      MATERIALS AND METHODS: According to the institutional review board-approved
      protocol, chart records were reviewed for all orthognathic surgical patients with
      a clinical, genetic, or muscle biopsy-proved diagnosis of CM or CMD. RESULTS: Six
      patients (5 male, 1 female) qualified, and they were treated by 4 surgeons in the
      division of oral and maxillofacial surgery from 1992 through 2007. Average age
      was 19.5 years at the time of orthognathic surgery. Five patients had Class III
      malocclusions and 1 patient had Class II malocclusion. All 6 patients had
      apertognathia with lip incompetence. Nasoendotracheal intubation with a
      difficulty of 0/3 (0=easiest, 3=most difficult) was performed in all cases.
      Routine induction and maintenance anesthetics, including halogenated agents and
      nondepolarizing muscle relaxants, were administered without malignant
      hyperthermia. All 6 patients underwent Le Fort level osteotomies; 4 also had
      mandibular setback surgery with or without balancing mandibular inferior border
      osteotomies. Five patients required planned intensive care unit care
      postoperatively (average, 18.4 days; range, 4 to 65 days). Postoperative
      respiratory complications resulting in major blood oxygen desaturations occurred
      in 5 patients; 4 of these patients required reintubation during emergency code
      response. Five patients required extended postoperative intubation (average, 4.2
      days; range, 3 to 6 days) and ventilatory support. Average hospital length of
      stay was 21.8 days (range, 6 to 75 days). Average postoperative follow-up
      interval was 29.8 weeks (range, 6 to 128 weeks). CONCLUSIONS: Patients with CMs
      or CMDs often have characteristic dentofacial malocclusions that contribute to
      functional problems with feeding and drooling and psychosocial problems.
      Orthognathic surgery, usually bimaxillary, can be judiciously considered in these
      patients; these procedures typically require multidisciplinary pre- and
      postoperative evaluation and care over lengthy hospital stays with a high risk of
      respiratory complications that bear consideration in treatment planning.

PMID- 26292176
TI  - Association of Thyroid Nodule Size and Bethesda Class With Rate of Malignant
      Disease.
AB  - IMPORTANCE: The ability to accurately stratify patients with thyroid nodules
      (TNs) preoperatively is imperative because most TNs are benign. The reliability
      of fine-needle aspiration biopsy (FNAB) in large TNs has been questioned in
      recent literature. OBJECTIVE: To determine whether TN size affects the
      reliability of FNAB results, and to determine the rates of malignant disease of
      each Bethesda class at Penn State Medical Center. DESIGN, SETTING, AND
      PARTICIPANTS: Retrospective electronic medical record review of patients
      undergoing FNAB followed by thyroidectomy from March 2010 through December 2013
      at an academic, tertiary referral center. A total of 297 patients with 326 TNs
      were identified as part of a consecutive series. MAIN OUTCOMES AND MEASURES: The
      primary outcome was to determine the rate of malignant disease of TNs smaller
      than 3.0 cm or 3.0 cm or larger and of each Bethesda class. Statistical analysis
      included chi(2) tests. The secondary outcome was to develop logistic regression
      models to estimate the probability of malignant disease on final pathologic
      diagnosis as predicted by TN size as well as TN size in conjunction with Bethesda
      class. RESULTS: Of the 297 patients, 233 were female (78.4%). The mean (SD) age
      was 51.0 (15.4) years. Of the 326 TNs, 143 were malignant on surgical
      histopathologic analysis (43.7%). The mean TN size was 2.0 (1.4) cm. Rates of
      malignant disease for Bethesda classes 1 to 6 were 0% (95% CI, 0%-26.0%), 6.0%
      (95% CI, 1.7%-14.6%), 30.2% (95% CI, 18.3%-44.3%), 23.5% (95% CI, 14.8%-34.2%),
      72.4% (95% CI, 52.8%-87.3%), and 98.8% (95% CI, 93.5%-99.9%), respectively.
      Overall sensitivity and specificity (excluding class 1 TNs) were 97.2% and 36.8%,
      respectively. The false-negative rate of benign cytologic results was 6.0% (95%
      CI, 1.7%-14.6%); only 1 false-negative result occurred in TNs 3.0 cm or greater.
      Of the TNs smaller than 3.0 cm, 48.4% were malignant compared with 33.3% of TNs
      3.0 cm or greater (P = .049). Both Bethesda class and TN size were significant
      variables (P < .05) within our logistic regression models indicating that higher
      Bethesda class and TN size smaller than about 2.0 cm were associated with
      increased probabilities of malignant disease. CONCLUSIONS AND RELEVANCE: Our
      results suggest that smaller TNs (smaller than about 2.0 cm) are associated with
      increased probabilities of malignant disease irrespective of Bethesda class.
      Routine diagnostic thyroid lobectomy solely owing to TN size of 3.0 cm or greater
      need not be performed.

PMID- 26292177
TI  - Explicit and implicit caregiving interests in expectant fathers: Do endogenous
      and exogenous oxytocin and vasopressin matter?
AB  - Caregiving interest in men (N=46) during the third trimester of their partner's
      pregnancy was examined. The study included both explicit and implicit measures of
      caregiving interest, assessments of basal urinary concentrations of oxytocin and
      vasopressin, and exogenous (intranasal) application of these hormones. Compared
      to control men (N=20), fathers-to-be reported more interest in direct care for
      children. In an immersive virtual environment, fathers-to-be, in comparison to
      control men, stood closer to and tended to spend more time looking at the baby
      related avatars, and stood further away and tended to spend less time looking at
      non-baby-related avatars. Basal oxytocin and vasopressin were not related to
      caregiving interest in fathers-to-be, and were not different from control men.
      When vasopressin was administered, fathers-to-be invested more time watching the
      baby-related avatars compared to control men. No effects were found of exogenous
      oxytocin on the behavior of fathers-to-be and control men in the immersive
      virtual environment. These results point in the direction of an adjustment of
      fathers-to-be for fatherhood, both consciously and unconsciously, and support the
      possible role of vasopressin in human behavior in the transition to fatherhood. 

PMID- 26292178
TI  - Individual cognitive stimulation therapy for dementia: a clinical effectiveness
      and cost-effectiveness pragmatic, multicentre, randomised controlled trial.
AB  - BACKGROUND: Group cognitive stimulation therapy programmes can benefit cognition
      and quality of life for people with dementia. Evidence for home-based, carer-led
      cognitive stimulation interventions is limited. OBJECTIVES: To evaluate the
      clinical effectiveness and cost-effectiveness of carer-delivered individual
      cognitive stimulation therapy (iCST) for people with dementia and their family
      carers, compared with treatment as usual (TAU). DESIGN: A multicentre, single
      blind, randomised controlled trial assessing clinical effectiveness and cost
      effectiveness. Assessments were at baseline, 13 weeks and 26 weeks (primary end
      point). SETTING: Participants were recruited through Memory Clinics and Community
      Mental Health Teams for older people. PARTICIPANTS: A total of 356 caregiving
      dyads were recruited and 273 completed the trial. INTERVENTION: iCST consisted of
      structured cognitive stimulation sessions for people with dementia, completed up
      to three times weekly over 25 weeks. Family carers were supported to deliver the
      sessions at home. MAIN OUTCOME MEASURES: Primary outcomes for the person with
      dementia were cognition and quality of life. Secondary outcomes included
      behavioural and psychological symptoms, activities of daily living, depressive
      symptoms and relationship quality. The primary outcome for the family carers was
      mental/physical health (Short Form questionnaire-12 items). Health-related
      quality of life (European Quality of Life-5 Dimensions), mood symptoms,
      resilience and relationship quality comprised the secondary outcomes. Costs were
      estimated from health and social care and societal perspectives. RESULTS: There
      were no differences in any of the primary outcomes for people with dementia
      between intervention and TAU [cognition: mean difference -0.55, 95% confidence
      interval (CI) -2.00 to 0.90; p-value = 0.45; self-reported quality of life: mean
      difference -0.02, 95% CI -1.22 to 0.82; p-value = 0.97 at the 6-month follow-up].
      iCST did not improve mental/physical health for carers. People with dementia in
      the iCST group experienced better relationship quality with their carer, but
      there was no evidence that iCST improved their activities of daily living,
      depression or behavioural and psychological symptoms. iCST seemed to improve
      health-related quality of life for carers but did not benefit carers' resilience
      or their relationship quality with their relative. Carers conducting more
      sessions had fewer depressive symptoms. Qualitative data suggested that people
      with dementia and their carers experienced better communication owing to iCST.
      Adjusted mean costs were not significantly different between the groups. From the
      societal perspective, both health gains and cost savings were observed.
      CONCLUSIONS: iCST did not improve cognition or quality of life for people with
      dementia, or carers' physical and mental health. Costs of the intervention were
      offset by some reductions in social care and other services. Although there was
      some evidence of improvement in terms of the caregiving relationship and carers'
      health-related quality of life, iCST does not appear to deliver clinical benefits
      for cognition and quality of life for people with dementia. Most people received
      fewer than the recommended number of iCST sessions. Further research is needed to
      ascertain the clinical effectiveness of carer-led cognitive stimulation
      interventions for people with dementia. TRIAL REGISTRATION: Current Controlled
      Trials ISRCTN65945963. FUNDING: This project was funded by the National Institute
      of Health Research (NIHR) Health Technology Assessment (HTA) programme and will
      be published in full in Health Technology Assessment; Vol. 19, No. 64. See the
      NIHR Journals Library website for further information.

PMID- 26292179
TI  - Chondroprotective effect of three different classes of anti-inflammatory agents
      on human osteoarthritic chondrocytes exposed to IL-1beta.
AB  - VA694, a promising cyclooxigenase-2 (COX-2)-inhibiting hybrid drug endowed with
      nitric oxide (NO) releasing properties (NO-COXIB), showed COX-2-selective
      inhibitory effects, associated with interesting anti-inflammatory and anti
      nociceptive activities. Therefore, we studied the effects of VA694 on cartilage
      metabolism, in comparison with Naproxcinod, a COX inhibitor and NO donor (CINOD),
      and Naproxen, a traditional non-steroidal-anti-inflammatory drug (NSAID) on human
      osteoarthritic chondrocyte cultures. IL-1beta-stimulated chondrocytes showed a
      significant decrease in cell viability (P<0.001). VA694, Naproxcinod and Naproxen
      alone didn't significantly affect cell viability, while it restored cell
      viability in cultures stimulated by IL-1beta. The presence of IL-1beta determined
      a significant increase (P<0.001) in PGE2 levels measured by an ELISA assay, and
      in COX-2 and MMP-3, -9, and -13 gene expression analyzed by RT-PCR. VA694,
      Naproxcinod and Naproxen, at both concentrations analyzed, significantly
      counteracted the negative effects induced by IL-1beta. VA694, Naproxcinod and
      Naproxen pre-treatment were able to inhibit IL-1beta-induced NF-kappaB
      activation, when measured as its nuclear translocation (p50 and p65 subunits).
      Naproxcinod and Naproxen pre-treatment didn't affect cytoplasmic NF-kappaB
      levels; VA694 decreased the cytoplasmic levels of both subunits. Our data suggest
      that VA694, Naproxcinod and Naproxen, exert anti-inflammatory and
      chondroprotective effects on OA chondrocytes.

PMID- 26292180
TI  - Total glucosides of paeony can reduce the hepatotoxicity caused by Methotrexate
      and Leflunomide combination treatment of active rheumatoid arthritis.
AB  - OBJECTIVE: Total glucosides of paeony (TGP) have been confirmed to exert anti
      inflammatory and hepatoprotective effects. Methotrexate (MTX) and Leflunomide
      (LEF) combination has a better efficacy in the treatment of active rheumatoid
      arthritis (RA), but hepatotoxicity was observed. In this study, we investigated
      the effect of TGP on hepatic dysfunction caused by MTX and LEF in patients with
      active RA. METHODS: A total of 268 patients with active RA (disease activity
      score in 28 joints, DAS28>3.2) were enrolled in this study. All patients were
      randomly assigned to two groups, the therapeutic group in which patients were
      treated with TGP (1.8 g/day) combined with MTX and LEF (MTX 10mg/week plus LEF
      20mg/day) while in the control group, patients were treated without TGP up to 12
      weeks. The efficacy and liver abnormalities were observed. RESULTS: The incidence
      of abnormal liver function within 12 weeks in TGP group was significantly lower
      than that in control group (11.38% vs 23.26%, P=0.013). The proportion of
      patients with ALT/AST >3 times ULN (upper limits of normal) was significantly
      lower in TGP group than control group (1.63% vs 7.75%, P=0.022). More patients
      achieved remission, good and moderate response in TGP group than control group at
      4, 8 and 12 weeks, but the difference was not significant (P>0.05). The
      proportions of all adverse events were comparable in the two groups except for
      diarrhea. CONCLUSIONS: Our study demonstrates that TGP can significantly reduce
      the incidence and severity of liver damage caused by MTX+LEF in the treatment of
      active RA patients.

PMID- 26292181
TI  - Foodborne Diseases Active Surveillance Network-2 Decades of Achievements, 1996
      2015.
AB  - The Foodborne Diseases Active Surveillance Network (FoodNet) provides a
      foundation for food safety policy and illness prevention in the United States.
      FoodNet conducts active, population-based surveillance at 10 US sites for
      laboratory-confirmed infections of 9 bacterial and parasitic pathogens
      transmitted commonly through food and for hemolytic uremic syndrome. Through
      FoodNet, state and federal scientists collaborate to monitor trends in enteric
      illnesses, identify their sources, and implement special studies. FoodNet's major
      contributions include establishment of reliable, active population-based
      surveillance of enteric diseases; development and implementation of epidemiologic
      studies to determine risk and protective factors for sporadic enteric infections;
      population and laboratory surveys that describe the features of gastrointestinal
      illnesses, medical care-seeking behavior, frequency of eating various foods, and
      laboratory practices; and development of a surveillance and research platform
      that can be adapted to address emerging issues. The importance of FoodNet's
      ongoing contributions probably will grow as clinical, laboratory, and informatics
      technologies continue changing rapidly. 

PMID- 26292182
TI  - Water Dispersible and Biocompatible Porphyrin-Based Nanospheres for Biophotonics
      Applications: A Novel Surfactant and Polyelectrolyte-Based Fabrication Strategy
      for Modifying Hydrophobic Porphyrins.
AB  - The hydrophobility of most porphyrin and porphyrin derivatives has limited their
      applications in medicine and biology. Herein, we developed a novel and general
      strategy for the design of porphyrin nanospheres with good biocompatibility and
      water dispersibility for biological applications using hydrophobic porphyrins. In
      order to display the generality of the method, we used two hydrophobic porphyrin
      isomers as starting material which have different structures confirmed by an X
      ray technique. The porphyrin nanospheres were fabricated through two main steps.
      First, the uniform porphyrin nanospheres stabilized by surfactant were prepared
      by an interfacially driven microemulsion method, and then the layer-by-layer
      method was used for the synthesis of polyelectrolyte-coated porphyrin nanospheres
      to reduce the toxicity of the surfactant as well as improve the biocompatibility
      of the nanospheres. The newly fabricated porphyrin nanospheres were characterized
      by TEM techniques, the electronic absorption spectra, photoluminescence emission
      spectra, dynamic light scattering, and cytotoxicity examination. The resulting
      nanospheres demonstrated good biocompatibility, excellent water dispersibility
      and low toxicity. In order to show their application in biophotonics, these
      porphyrin nanospheres were successfully applied in targeted living cancer cell
      imaging. The results showed an effective method had been explored to prepare
      water dispersible and highly stable porphyrin nanomaterial for biophotonics
      applications using hydrophobic porphyrin. The approach we reported shows obvious
      flexibility because the surfactants and polyelectrolytes can be optionally
      selected in accordance with the characteristics of the hydrophobic material. This
      strategy will expand the applications of hydrophobic porphyrins owning excellent
      properties in medicine and biology. 

PMID- 26292184
TI  - Additive antinociceptive effects of mixtures of the kappa-opioid receptor agonist
      spiradoline and the cannabinoid receptor agonist CP55940 in rats.
AB  - Pain is a significant clinical problem, and there is a need for pharmacotherapies
      that are more effective with fewer adverse effects than currently available
      medications. Cannabinoid receptor agonists enhance the antinociceptive effects of
      MU-opioid receptor agonists; it is unclear whether they impact the effects of
      agonists acting at other opioid receptors. kappa-Opioid receptor agonists have
      antinociceptive effects, but their clinical use is precluded by adverse effects;
      however, their therapeutic potential might be realized if antinociceptive effects
      could be selectively enhanced. In this study, the antinociceptive effects of the
      cannabinoid receptor agonist CP55940 and the kappa-opioid receptor agonist
      spiradoline, alone and in combination, were studied in rats (n=7) using a warm
      water tail-withdrawal procedure. When administered alone, CP55940 (0.032-1.0
      mg/kg) and spiradoline (1.0-32.0 mg/kg) increased tail-withdrawal latency, and
      mixtures of CP55940 and spiradoline (ratios of 1 : 3, 1 : 1, and 3 : 1) produced
      additive effects. It remains to be determined whether this additive interaction
      between a kappa-opioid receptor agonist and a cannabinoid receptor agonist is
      selective for antinociception and whether it can be generalized to other drugs. 

PMID- 26292183
TI  - Autophagy supports color vision.
AB  - Cones comprise only a small portion of the photoreceptors in mammalian retinas.
      However, cones are vital for color vision and visual perception, and their loss
      severely diminishes the quality of life for patients with retinal degenerative
      diseases. Cones function in bright light and have higher demand for energy than
      rods; yet, the mechanisms that support the energy requirements of cones are
      poorly understood. One such pathway that potentially could sustain cones under
      basal and stress conditions is macroautophagy. We addressed the role of
      macroautophagy in cones by examining how the genetic block of this pathway
      affects the structural integrity, survival, and function of these neurons. We
      found that macroautophagy was not detectable in cones under normal conditions but
      was readily observed following 24 h of fasting. Consistent with this, starvation
      induced phosphorylation of AMPK specifically in cones indicating cellular
      starvation. Inhibiting macroautophagy in cones by deleting the essential
      macroautophagy gene Atg5 led to reduced cone function following starvation
      suggesting that cones are sensitive to systemic changes in nutrients and activate
      macroautophagy to maintain their function. ATG5-deficiency rendered cones
      susceptible to light-induced damage and caused accumulation of damaged
      mitochondria in the inner segments, shortening of the outer segments, and
      degeneration of all cone types, revealing the importance of mitophagy in
      supporting cone metabolic needs. Our results demonstrate that macroautophagy
      supports the function and long-term survival of cones providing for their unique
      metabolic requirements and resistance to stress. Targeting macroautophagy has the
      potential to preserve cone-mediated vision during retinal degenerative diseases. 

PMID- 26292185
TI  - Timing of SCH 23390 administration influences extinction of conditioned
      hyperactivity in mice.
AB  - The precise role of the dopamine subtype-1 (D1) receptor in differentially
      mediating extinction-related processes (memory retrieval vs. memory
      reconsolidation) in the conditioned hyperactivity paradigm is unknown. Thus, the
      present experiments determined the effect of a selective D1 receptor antagonist,
      SCH 23390, on extinction of conditioned hyperactivity when SCH 23390 was
      administered immediately after (memory reconsolidation; experiment 1) or before
      (memory retrieval; experiment 2) extinction sessions. Male, Swiss-Webster mice
      received subcutaneous injections of methamphetamine (1.0 mg/kg) associated with
      locomotor activity chambers (paired) or in their home cages (unpaired) during the
      acquisition phase. Following acquisition, paired and unpaired mice received an
      intraperitoneal injection of either vehicle (physiological saline) or SCH 23390
      (0.0125, 0.025, 0.05 mg/kg) immediately after (experiment 1) or received vehicle
      or SCH 23390 (0.05 mg/kg) 30 min before (experiment 2), daily extinction
      sessions. Methamphetamine produced robust conditioned hyperactivity, followed by
      extinction. Furthermore, SCH 23390 (0.05 mg/kg) blocked expression of conditioned
      hyperactivity, without nonspecifically impairing locomotor activity, when
      administered before the extinction session, but did not alter the rate of
      extinction when administered immediately following the sessions. Taken together,
      these results suggest that the D1 receptor is involved in memory retrieval, but
      not memory reconsolidation, processes during extinction of conditioned
      hyperactivity. 

PMID- 26292186
TI  - Neuronal calcium/calmodulin-dependent protein kinase II mediates nicotine reward
      in the conditioned place preference test in mice.
AB  - Several recent studies have indicated the involvement of calcium-dependent
      mechanisms, in particular the abundant calcium-activated kinase,
      calcium/calmodulin-dependent kinase II (CaMKII), in behaviors associated with
      nicotine dependence in mice. Behavioral and biochemical studies have shown that
      CaMKII is involved in acute and chronic nicotine behaviors and nicotine
      withdrawal; however, evidence of a role for CaMKII in nicotine reward is lacking.
      Thus, the goal of the current study was to examine the role of CaMKII in nicotine
      reward. Using pharmacological and genetic tools, we tested nicotine conditioned
      place preference (CPP) in C57Bl/6 mice after administration of CaMKII antagonists
      and in alpha-CaMKII wild-type (+/+) and heterozygote (+/-) mice. CaMKII
      antagonists blocked expression of nicotine CPP, and the preference score was
      significantly reduced in alpha-CaMKII +/- mice compared with their +/+
      counterparts. Further, we assessed CaMKII activity in the ventral tegmental area
      (VTA), nucleus accumbens (NAc), prefrontal cortex, and hippocampus after nicotine
      CPP and found significant increases in CaMKII activity in the mouse VTA and NAc
      that were blocked by CaMKII antagonists. The findings from this study show that
      CaMKII mediates nicotine reward and suggest that increases in CaMKII activity in
      the VTA and NAc are relevant to nicotine reward behaviors. 

PMID- 26292187
TI  - 5-HT2A and mGlu2/3 receptor interactions: on their relevance to cognitive
      function and psychosis.
AB  - Serotonin [5-hydroxytryptamine (5-HT)] and glutamate have both been implicated in
      the pathophysiology of neuropsychiatric disorders but also in the mechanism of
      antipsychotic and hallucinogenic drug actions. Furthermore, close antagonistic
      interactions between 5-HT2A and metabotropic glutamate (mGlu)2/3 receptors have
      been established over the last decades on the basis of numerous
      electrophysiological, biochemical, and behavioral studies. Besides synaptic
      mechanisms, more recent findings suggested that heterodimeric 5-HT2A-mGlu2
      receptor complexes in the prefrontal cortex may account for the functional
      crosstalk between these two receptor subtypes. In this review, we focus on in
      vitro and in-vivo studies documenting the important relationship between 5-HT2A
      and mGlu2/3 receptors, with relevance to both normal behavioral function and
      psychosis. 

PMID- 26292188
TI  - Blockade of GPR55 in the dorsolateral striatum impairs performance of rats in a T
      maze paradigm.
AB  - To investigate the role of GPR55 receptors, which are expressed in human and rat
      striatum (a structure that regulates procedural memory), Wistar rats received
      five training sessions (10 trials/session, 1 session/day) to solve a T-maze
      paradigm. From these data, we constructed learning curves following
      pharmacological manipulation of GPR55. Five minutes before each session, animals
      received bilateral intradorsolateral striatum injections of noladin-ether (3.1
      nmol/l; endogenous agonist of GPR55 and CB1 receptors), CID16020036 (5.6 nmol/l;
      GPR55 antagonist), AM251 (5.6 nmol/l; CB1 antagonist), or a combination of
      noladin-ether with each antagonist. Noladin-ether by itself induced no
      significant changes in the learning curve. Nevertheless, while simultaneously
      blocking CB1 receptors (with AM251), noladin-ether improved acquisition. In
      contrast, while simultaneously blocking GPR55 (with CID16020036), noladin-ether
      weakened acquisition. CID16020036 by itself impaired learning, whereas AM251 by
      itself reduced the efficiency in the task. There were no differences between
      groups in the latency to reach the arms from the starting point; thus, no motor
      coordination impairments interfered with this task. These results strongly
      suggest a role of GPR55 in procedural memory and constitute the first evidence
      indicating that this receptor regulates cognitive processes.

PMID- 26292190
TI  - Cardiotoxicity of anticancer treatments.

PMID- 26292189
TI  - Cocaine-induced reward enhancement measured with intracranial self-stimulation in
      rats bred for low versus high saccharin intake.
AB  - Rats selectively bred for high (HiS) or low (LoS) saccharin intake are a well
      established model of drug-abuse vulnerability, with HiS rats being more likely to
      consume sweets and cocaine than LoS rats. Still, the nature of these differences
      is poorly understood. This study examined whether the motivational consequences
      of cocaine exposure are differentially expressed in HiS and LoS rats by measuring
      intracranial self-stimulation (ICSS) thresholds following acute injections of
      cocaine (10 mg/kg). Reductions in ICSS thresholds following cocaine injection
      were greater in HiS rats than in LoS rats, suggesting that the reward-enhancing
      effects of cocaine are greater in the drug-vulnerable HiS than LoS rats. Higher
      cocaine-induced reward, indicated by lower ICSS thresholds, may explain the
      higher rates of drug consumption in sweet-preferring animal models, providing a
      clue to the etiology of cocaine addiction in vulnerable populations. 

PMID- 26292191
TI  - Relationships between serum asunaprevir concentration and alanine
      aminotransferase elevation during daclatasvir plus asunaprevir for chronic HCV
      genotype 1b infection.
AB  - Alanine aminotransferase (ALT) elevations were the most frequent adverse events
      during all-oral combinations with daclatasvir and asunaprevir for patients with
      hepatitis C virus (HCV) infection, but the underline mechanisms are unclear.
      Seventy patients with chronic HCV genotype 1b infection, who were introduced
      daclatasvir 60 mg once daily plus asunaprevir 100 mg twice daily for 24 weeks,
      were measured serum asunaprevir concentrations at the one point or more of 2, 4,
      and 8 weeks after the start of treatment. In 4 and 8 weeks after the start of
      treatment, asunaprevir concentrations in patients with albumin levels <3.6 g/dl
      at baseline were significantly higher than those in patients with albumin levels
      >=3.6 g/dl. The baseline factors did not affect to ALT severe elevations (>=300
      IU/l). At 2 weeks after the start of treatment, ALT severe elevations with
      asunaprevir concentrations of >=800 ng/ml (54.5%) tended to indicate the higher
      rates than those of <800 ng/ml (17.6%). Furthermore, the discontinuation or
      reduction of asunaprevir improved ALT levels, regardless the significant decrease
      of serum asunaprevir concentrations. In conclusion, serum albumin levels affected
      to serum asunaprevir concentrations, and serum asunaprevir concentrations might
      partly affect to ALT severe elevations. Further large-scale prospective studies
      are needed to investigate the impact of the discontinuation or reduction of
      asunaprevir to help in the design of more effective therapeutic regimens.

PMID- 26292192
TI  - Patient financial responsibility for observation care.
AB  - BACKGROUND: As observation care grows, Medicare beneficiaries are increasingly
      likely to revisit observation care instead of being readmitted. This trend has
      potential financial implications for Medicare beneficiaries because observation
      care-although typically hospital based-is classified as an outpatient service.
      Beneficiaries who are readmitted pay the inpatient deductible only once per
      benefit period. In contrast, beneficiaries who have multiple care episodes under
      observations status are subject to coinsurance at every stay and could accrue
      higher cumulative costs. OBJECTIVES: We were interested in answering the
      question: Do Medicare beneficiaries who revisit observation care pay more than
      they would have had they been readmitted? DESIGN: We used a 20% sample of the
      Medicare Outpatient Standard Analytic File (2010-2012) to determine the total
      cumulative financial liability for Medicare beneficiaries who revisit observation
      care multiple times within a 60-day period. PARTICIPANTS: Participants were fee
      for-service Medicare beneficiaries who had Part A and Part B coverage for a full
      calendar year (or until death) during the study period. MEASUREMENTS: Our primary
      measure was beneficiary financial responsibility for facilities fees. RESULTS: On
      average, beneficiaries with multiple observation stays in a 60-day period had a
      cumulative financial liability of $947.40 (803.62), which is significantly lower
      than the $1100 inpatient deductible (P < 0.01). However, 26.6% of these
      beneficiaries had a cumulative financial liability that exceeded the inpatient
      deductible. CONCLUSIONS: More than a quarter of Medicare beneficiaries with
      multiple observation stays in a 60-day time period have a higher financial
      liability than they would have had under Part A benefits.

PMID- 26292193
TI  - The Frequency of Postreduction Interventions After Successful Enema Reduction of
      Intussusception.
AB  - OBJECTIVES: The objective was to determine the frequency of postreduction,
      hospital-level interventions among children with successful reduction of
      ileocolic intussusception and identify factors that predict the need for such
      interventions. METHODS: This was a retrospective cross-sectional study of
      children who underwent successful enema reduction for ileocolic intussusception
      at a single emergency department. Hospital-level interventions were included if
      they occurred within 24 hours of reduction and were further classified as either
      major (recurrence or possible perforation) or minor (imaging for suspected
      recurrence or administration of parenteral narcotics or antiemetics). Binary
      logistic regression was used to identify predictors for hospital-level
      interventions. RESULTS: A total of 464 children underwent enema reduction. The
      median age was 1.7 years (interquartile range [IQR] = 0.8 to 2.5 years), and 66%
      were male. A total of 435 (94%) were hospitalized with a median hospital stay of
      25 hours (IQR = 19 to 34 hours). Nineteen percent (95% confidence interval [CI] =
      15% to 22%) needed postreduction interventions, including 6% (95% CI = 4% to 9%)
      who required major interventions. The median time to any hospital intervention
      was 9.9 hours (IQR = 6.3 to 16.4 hours). We identified two independent predictors
      for hospital-level interventions: duration of symptoms > 24 hours (adjusted odds
      ratio [OR] = 2.1, 95% CI = 1.3 to 3.4) and location of the intussusception tip at
      (or proximal to) the hepatic flexure (adjusted OR = 1.9, 95% CI = 1.1 to 3.3);
      the latter factor was also a predictor of a major intervention. None of the
      children (95% CI = 0 to 1.0%) had an acute decompensation after an initially
      successful enema reduction. CONCLUSIONS: Clinical decompensation is rare and
      recurrence is relatively low after an uncomplicated reduction of ileocolic
      intussusception. However, one in five children required hospital-level
      interventions after reduction. Children with the intussusception tip at (or
      proximal to) the hepatic flexure, and those with symptoms for longer than 24
      hours, are more likely to require subsequent interventions. Although outpatient
      management appears safe after a period of observation, caregivers should be
      counseled about the risk of ongoing symptoms and recurrence.

PMID- 26292194
TI  - Cotranslational folding of deeply knotted proteins.
AB  - Proper folding of deeply knotted proteins has a very low success rate even in
      structure-based models which favor formation of the native contacts but have no
      topological bias. By employing a structure-based model, we demonstrate that
      cotranslational folding on a model ribosome may enhance the odds to form trefoil
      knots for protein YibK without any need to introduce any non-native contacts. The
      ribosome is represented by a repulsive wall that keeps elongating the protein. On
      ribosome folding proceeds through a a slipknot conformation. We elucidate the
      mechanics and energetics of its formation. We show that the knotting probability
      in on-ribosome folding is a function of temperature and that there is an optimal
      temperature for the process. Our model often leads to the establishment of the
      native contacts without formation of the knot. 

PMID- 26292195
TI  - Effects of pulsed atrazine exposures on autotrophic community structure, biomass,
      and production in field-based stream mesocosms.
AB  - The authors performed a multiple-pulsed atrazine experiment to measure responses
      of autotrophic endpoints in outdoor stream mesocosms. The experiment was designed
      to synthetically simulate worst-case atrazine chemographs from streams in
      agricultural catchments to achieve 60-d mean concentrations of 0 MUg/L (control),
      10 MUg/L, 20 MUg/L, and 30 MUg/L. The authors dosed triplicate streams with
      pulses of 0 MUg/L, 50 MUg/L, 100 MUg/L, and 150 MUg/L atrazine for 4 d, followed
      by 7 d without dosing. This 11-d cycle occurred 3 times, followed by a recovery
      (untreated) period from day 34 to day 60. Mean +/- standard error 60-d atrazine
      concentrations were 0.07 +/- 0.03 MUg/L, 10.7 +/- 0.05 MUg/L, 20.9 +/- 0.24
      MUg/L, and 31.0 +/- 0.17 MUg/L for the control, 10-MUg/L, 20-MUg/L, and 30-MUg/L
      treatments, respectively. Multivariate analyses revealed that periphyton and
      phytoplankton community structure did not differ among treatments on any day of
      the experiment, including during the atrazine pulses. Control periphyton biomass
      in riffles was higher immediately following the peak of the first atrazine pulse
      and remained slightly higher than some of the atrazine treatments on most days
      through the peak of the last pulse. However, periphyton biomass was not different
      among treatments at the end of the present study. Phytoplankton biomass was not
      affected by atrazine. Metaphyton biomass in pools was higher in the controls near
      the midpoint of the present study and remained higher on most days for the
      remainder of the study. Ceratophyllum demersum, a submersed macrophyte, biomass
      was higher in controls than in 20-MUg/L and 30-MUg/L treatments before pulse 3
      but was not different subsequent to pulse 3 through the end of the present study.
      Maximum daily dissolved oxygen (DO, percentage of saturation) declined during
      each pulse in approximate proportion to magnitude of dose but rapidly converged
      among treatments after the third pulse. However, DO increased in controls
      relative to all atrazine treatments during the last 17 d of the experiment,
      likely a result of metaphyton cover in the pools. Finally, atrazine significantly
      limited uptake of PO4(3-) and uptake and/or denitrification of NO3(-) but only
      during pulses; percentage of dose removed from the water column was >85% for P
      and >95% for N after pulse 3 through the end of the present study. Collectively,
      only DO and metaphyton biomass differed at the end of the present study and only
      slightly. Some other endpoints were affected but only during pulses, if at all.
      The high levels of primary production and accumulation of algal biomass in all
      streams suggest that effects of pulses of atrazine at the concentrations used in
      the present study appear transient and likely do not represent ecologically
      significant adverse outcomes to periphyton, phytoplankton, and aquatic
      macrophytes, particularly in agricultural streams subjected to high nutrient
      loads.

PMID- 26292196
TI  - Markers of Psychological Differences and Social and Health Inequalities: Possible
      Genetic and Phenotypic Overlaps.
AB  - Associations between markers of ostensible psychological characteristics and
      social and health inequalities are pervasive but difficult to explain. In some
      cases, there may be causal influence flowing from social and health inequalities
      to psychological differences, whereas sometimes it may be the other way around.
      Here, we focus on the possibility that some markers that we often consider as
      indexing different domains of individual differences may in fact reflect at least
      partially overlapping genetic and/or phenotypic bases. For example, individual
      differences in cognitive abilities and educational attainment appear to reflect
      largely overlapping genetic influences, whereas cognitive abilities and health
      literacy may be almost identical phenomena at the phenotypic, never mind genetic,
      level. We make the case for employing molecular genetic data and quantitative
      genetic techniques to better understand the associations of psychological
      individual differences with social and health inequalities. We illustrate these
      arguments by using published findings from the Lothian Birth Cohort and the
      Generation Scotland studies. We also present novel findings pertaining to
      longitudinal stability and change in older age personality traits and some
      correlates of the change, molecular genetic data-based heritability estimates of
      Neuroticism and Extraversion, and the genetic correlations of these personality
      traits with markers of social and health inequalities.

PMID- 26292197
TI  - Chelator free gallium-68 radiolabelling of silica coated iron oxide nanorods via
      surface interactions.
AB  - The commercial availability of combined magnetic resonance imaging (MRI)/positron
      emission tomography (PET) scanners for clinical use has increased demand for
      easily prepared agents which offer signal or contrast in both modalities. Herein
      we describe a new class of silica coated iron-oxide nanorods (NRs) coated with
      polyethylene glycol (PEG) and/or a tetraazamacrocyclic chelator (DO3A). Studies
      of the coated NRs validate their composition and confirm their properties as in
      vivo T2 MRI contrast agents. Radiolabelling studies with the positron emitting
      radioisotope gallium-68 (t1/2 = 68 min) demonstrate that, in the presence of the
      silica coating, the macrocyclic chelator was not required for preparation of
      highly stable radiometal-NR constructs. In vivo PET-CT and MR imaging studies
      show the expected high liver uptake of gallium-68 radiolabelled nanorods with no
      significant release of gallium-68 metal ions, validating our innovation to
      provide a novel simple method for labelling of iron oxide NRs with a radiometal
      in the absence of a chelating unit that can be used for high sensitivity liver
      imaging. 

PMID- 26292198
TI  - Progression of anemia and its relationship with renal function, blood pressure,
      and erythropoietin in rats with chronic kidney disease.
AB  - BACKGROUND: In chronic kidney disease (CKD), anemia and hypertension are
      significant co-morbidities that contribute to cardiovascular and renal disease
      progression. OBJECTIVE: The purpose of the study was to identify correlations
      between changes in hematologic variables against markers of renal function, blood
      pressure, and erythropoietin (EPO) in a naturally occurring hypertensive model of
      CKD, the Lewis polycystic kidney (LPK) rat. METHODS: Complete blood count,
      systolic blood pressure, urea and creatinine concentration, urinary protein to
      creatinine ratio, and plasma EPO concentration were determined in control Lewis
      (n = 51) and LPK rats (n = 56) aged 6-24 weeks. Renal EPO gene expression and RBC
      osmotic fragility were also documented. Hematopoiesis in spleen and bone marrow
      were assessed. RESULTS: Lewis polycystic kidney rats had increasing urea and
      creatinine concentrations, concurrent with the development of a nonregenerative
      normocytic/normochromic anemia and hypertension, with a significant negative
      correlation between both HGB and HCT with urea concentration and blood pressure
      (P < .01). HCT was also significantly negatively correlated with creatinine
      concentration (P = .014). WBC was significantly negatively correlated with urea
      (P < .01). Plasma EPO concentration was increased and renal EPO mRNA expression
      was significantly upregulated in LPK animals. The former was significantly
      positively correlated with blood pressure and platelet count (P < .05). RBC
      osmotic fragility was normal in LPK rats and there was no evidence for increased
      RBC elimination or extramedullary hematopoiesis. CONCLUSIONS: Marked anemia in
      the LPK CKD rodent model in the presence of elevated EPO suggests inefficient
      erythropoiesis that is correlated with plasma urea concentration and blood
      pressure.

PMID- 26292199
TI  - Imaging of fast chlorophyll fluorescence induction curve (OJIP) parameters,
      applied in a screening study with wild barley (Hordeum spontaneum) genotypes
      under heat stress.
AB  - We quantified the influence of heat stress (HS) on PSII by imaging of parameters
      of the fast chlorophyll fluorescence (CF) induction (OJIP) kinetic of 20
      genotypes of wild barley (Hordeum spontaneum) covering a broad geographical
      spectrum. We developed a standardised screening procedure, allowing a repetitive
      fluorescence measurement of leaf segments. The impact of HS was quantified by
      calculating a Heat Resistance Index (HRI), derived from the decrease of the
      Performance Index (PI) caused by HS treatment and following recovery. For the
      genotype showing the lowest HRI, reduced maximum quantum yield (phiP0) and
      increased relative variable fluorescence of the O-J phase (K-Peak) were detected
      after HS, whereas the basal fluorescence (F0) remained stable. An additional
      feature was a lowered fraction of active (QA-reducing) reaction centres (RCs).
      The disturbances disappeared after one day of recovery. Spatial heterogeneities
      of fluorescence parameters were detected, as the negative effect of HS was
      stronger in the leaf areas close to the leaf tip. The results of this study prove
      that chlorophyll fluorescence imaging (CFI) is suitable for the detection of HS
      symptoms and that imaging of JIP-Test parameters should be considered in future
      screening and phenotyping studies aiming for the characterisation of plant
      genotypes. 

PMID- 26292200
TI  - Effects of Variations in Ligand Density on Cell Signaling.
AB  - Multiple simultaneous interactions between receptors and ligands dictate the
      extracellular and intracellular activities of cells. The concept of programmable
      ligand display is generally used to study the interaction between ligands,
      displayed on surfaces at various densities, with receptors present on cell
      surfaces. Various strategies are discussed here to display ligands on surfaces to
      study their effect on cell behavior. Only very few strategies have been reported
      where this display combines precise control over density with lateral spacing of
      ligands on surfaces. In this review, selected examples of strategies to control
      ligand density and spacing and their implications for biological functions of
      cells are discussed. 

PMID- 26292202
TI  - Control of Skin Potential by Triboelectrification with Ferroelectric Polymers.
AB  - Negatively polarized ferroelectric polymer beta-P(VDF-TrFE) shows higher positive
      triboelectric properties than skin, which could lead to new medical applications.
      Kelvin force microscope measurements and triboelectric nanogenerator
      characterizations are performed to demonstrate this new property. In addition,
      how many negative charges are exchanged by contact electrification between the
      negatively polarized beta-P(VDF-TrFE) and the skin is estimated. 

PMID- 26292201
TI  - Induction of stem-cell-derived functional neurons by NanoScript-based gene
      repression.
AB  - Even though gene repression is a powerful approach to exogenously regulate
      cellular behavior, developing a platform to effectively repress targeted genes,
      especially for stem-cell applications, remains elusive. Herein, we introduce a
      nanomaterial-based platform that is capable of mimicking the function of
      transcription repressor proteins to downregulate gene expression at the
      transcriptional level for enhancing stem-cell differentiation. We developed the
      "NanoScript" platform by integrating multiple gene repression molecules with a
      nanoparticle. First, we show a proof-of-concept demonstration using a GFP
      specific NanoScript to knockdown GFP expression in neural stem cells (NSCs-GFP).
      Then, we show that a Sox9-specific NanoScript can repress Sox9 expression to
      initiate enhanced differentiation of NSCs into functional neurons. Overall, the
      tunable properties and gene-knockdown capabilities of NanoScript enables its
      utilization for gene-repression applications in stem cell biology. 

PMID- 26292203
TI  - Transition-Metal-Free Dehydrosilylative Difluoroamidation of
      Tetrahydroisoquinolines under Mild Conditions.
AB  - Disclosed herein is a dehydrosilylative difluoroamidation of alpha-Csp(3)-H of
      tetrahydroisoquinolines with alpha,alpha-difluoro-alpha-TMS-acetamides. The
      process, which occurs at ambient temperature in the absence of any transition
      metals, provides direct access to a broad range of alpha,alpha-difluoroacetamide
      substituted tertiary amine derivatives in high yields. Moreover, the method was
      successfully applied in the Csp(3)-H-directed difluorophosphorylation and
      difluorocarboxylation under the same conditions. 

PMID- 26292204
TI  - Contact Lens Wearer Demographics and Risk Behaviors for Contact Lens-Related Eye
      Infections--United States, 2014.
AB  - Contact lenses provide safe and effective vision correction for many Americans.
      However, contact lens wearers risk infection if they fail to wear, clean,
      disinfect, and store their contact lenses as directed. Over the past decade, CDC
      has investigated several multistate outbreaks of serious eye infections among
      contact lens wearers, including Acanthamoeba keratitis. Each investigation
      identified frequent contact lens hygiene-related risk behaviors among patients.
      To guide prevention efforts, a population-based survey was used to estimate the
      number of contact lens wearers aged >=18 years in the United States. A separate
      online survey of contact lens wearers assessed the prevalence of contact lens
      hygiene-related risk behaviors. Approximately 99% of wearers reported at least
      one contact lens hygiene risk behavior. Nearly one third of contact lens wearers
      reported having experienced a previous contact lens-related red or painful eye
      requiring a doctor's visit. An estimated 40.9 million U.S. adults wear contact
      lenses, and many could be at risk for serious eye infections because of poor
      contact lens wear and care behaviors. These findings have informed the creation
      of targeted prevention messages aimed at contact lens wearers such as keeping all
      water away from contact lenses, discarding used disinfecting solution from the
      case and cleaning with fresh solution each day, and replacing their contact lens
      case every 3 months. 

PMID- 26292205
TI  - CDC Grand Rounds: Getting Smart About Antibiotics.
AB  - Each year in the United States, approximately two million persons become infected
      with antibiotic-resistant bacteria, at least 23,000 persons die as a direct
      result of these infections, and many more die from conditions complicated by a
      resistant infection. Antibiotic-resistant infections contribute to poor health
      outcomes, higher health care costs, and use of more toxic treatments. Although
      emerging resistance mechanisms are being identified and resistant infections are
      on the rise, new antibiotic development has slowed considerably. 

PMID- 26292206
TI  - Occupational Hydrofluoric Acid Injury from Car and Truck Washing--Washington
      State, 2001-2013.
AB  - Exposure to hydrofluoric acid (HF) causes corrosive chemical burns and
      potentially fatal systemic toxicity. Car and truck wash cleaning products, rust
      removers, and aluminum brighteners often contain HF because it is efficient in
      breaking down roadway matter. The death of a truck wash worker from ingestion of
      an HF-based wash product and 48 occupational HF burn cases associated with car
      and truck washing in Washington State during 2001-2013 are summarized in this
      report. Among seven hospitalized workers, two required surgery, and all but one
      worker returned to the job. Among 48 injured workers, job titles were primarily
      auto detailer, car wash worker, truck wash worker, and truck driver. Because HF
      exposure can result in potentially severe health outcomes, efforts to identify
      less hazardous alternatives to HF-based industrial wash products are warranted. 

PMID- 26292207
TI  - Progress Toward Poliomyelitis Eradication--Nigeria, January 2014-July 2015.
AB  - Since the 1988 launch of global poliomyelitis eradication efforts, four of the
      six World Health Organization (WHO) regions have been certified polio-free.
      Nigeria is one of only three countries, along with Afghanistan and Pakistan,
      where transmission of wild poliovirus (WPV) has never been interrupted. During
      2003-2013, northern Nigeria served as a reservoir for WPV reintroduction into 26
      previously polio-free countries. In 2012, the Nigerian government launched a
      national polio eradication emergency plan to intensify efforts to interrupt WPV
      transmission. This report describes polio eradication activities and progress in
      Nigeria during January 2014-July 2015 and updates previous reports. No WPV cases
      have been reported to date in 2015, compared with a total of six cases reported
      during 2014. Onset of paralysis in the latest reported WPV type 1 (WPV1) case was
      July 24, 2014. Only one case of circulating vaccine-derived poliovirus type 2
      (cVDPV2) has been reported to date in 2015, compared with 20 cVDPV2 cases during
      the same period in 2014. Pending final laboratory testing of 218 remaining
      specimens of 16,617 specimens collected since January 2015, Nigeria could be
      removed from the WHO list of polio-endemic countries in September 2015. Major
      remaining challenges to the national polio eradication program include sustaining
      political support and program funding in the absence of active WPV transmission,
      maintaining high levels of population immunity in hard-to-reach areas, and
      accessing children in security-compromised areas of the northeastern states. 

PMID- 26292208
TI  - Lead Poisoning and Anemia Associated with Use of Ayurvedic Medications Purchased
      on the Internet--Wisconsin, 2015.
AB  - On April 30, 2015, the Wisconsin Division of Public Health (WDPH) was notified by
      a local health department of an elevated blood lead level (BLL) in a female
      patient aged 64 years. All Wisconsin laboratories are required to provide BLL
      testing results performed on any state resident to WDPH, and WDPH and local
      health departments are statutorily mandated to investigate any single BLL >=20
      ug/dL or BLLs that are persistently >=15 ug/dL. Review of medical records
      revealed that the patient had developed progressive fatigue and shortness of
      breath during a period of multiple weeks that prompted inpatient medical
      evaluation. Hemoglobin level was 8.3 g/dL (normal range for age and sex of
      patient = 12.5-15.0 g/dL), and peripheral blood smear showed normochromic,
      normocytic red blood cells with basophilic stippling. A BLL was obtained and
      found to be 85.8 ug/dL. Urine toxic metals tests revealed mercury and aluminum
      levels in the normal range. Combined methylated and inorganic urine arsenic
      levels were slightly elevated at 53.3 ug/L (normal = <18.9 ug/L). The patient was
      discharged for outpatient lead chelation therapy with oral meso-2,3
      dimercaptosuccinic acid. 

PMID- 26292209
TI  - Assessment of the root system of Brassica juncea (L.) czern. and Bidens pilosa L.
      exposed to lead polluted soils using rhizobox systems.
AB  - The purpose of this study was to compare the behavior of the root system of one
      of the most frequently cited species in phytoremediation Indian mustard [Brassica
      juncea (L.) Czern.] and a representative perennial herb (Bidens pilosa L.) native
      of Argentina, for different concentrations of lead in soils through chemical and
      visualization techniques of the rhizosphere. Lead polluted soils from the
      vicinity of a lead recycling plant in the locality of Bouwer, were used in
      juxtaposed rhizobox systems planted with seedlings of B. juncea and B. pilosa
      with homogeneous and heterogeneous soil treatments. Root development, pH changes
      in the rhizosphere, dry weight biomass, lead content of root and aerial parts and
      potential extraction of lead by rhizosphere exudates were determined. In both
      species lead was mainly accumulated in roots. However, although B. juncea
      accumulated more lead than B. pilosa at elevated concentrations in soils, the
      latter achieved greater root and aerial development. No changes in the pH of the
      rhizosphere associated to lead were observed, despite different extractive
      potentials of lead in the exudates of the species analyzed. Our results indicated
      that Indian mustard did not behave as a hyperaccumulator in the conditions of the
      present study. 

PMID- 26292210
TI  - Trans-Reactivation: A New Epigenetic Phenomenon Underlying Transcriptional
      Reactivation of Silenced Genes.
AB  - In order to study the role played by cellular RNA pools produced by homologous
      genomic loci in defining the transcriptional state of a silenced gene, we tested
      the effect of non-functional alleles of the white gene in the presence of a
      functional copy of white, silenced by heterochromatin. We found that non
      functional alleles of white, unable to produce a coding transcript, could
      reactivate in trans the expression of a wild type copy of the same gene silenced
      by heterochromatin. This new epigenetic phenomenon of transcriptional trans
      reactivation is heritable, relies on the presence of homologous RNA's and is
      affected by mutations in genes involved in post-transcriptional gene silencing.
      Our data suggest a general new unexpected level of gene expression control
      mediated by homologous RNA molecules in the context of heterochromatic genes. 

PMID- 26292212
TI  - Correction: The Tinkerbell (Tink) Mutation Identifies the Dual-Specificity MAPK
      Phosphatase INDOLE-3-BUTYRIC ACID-RESPONSE5 (IBR5) as a Novel Regulator of Organ
      Size in Arabidopsis.

PMID- 26292211
TI  - VSX2 and ASCL1 Are Indicators of Neurogenic Competence in Human Retinal
      Progenitor Cultures.
AB  - Three dimensional (3D) culture techniques are frequently used for CNS tissue
      modeling and organoid production, including generation of retina-like tissues. A
      proposed advantage of these 3D systems is their potential to more closely
      approximate in vivo cellular microenvironments, which could translate into
      improved manufacture and/or maintenance of neuronal populations. Visual System
      Homeobox 2 (VSX2) labels all multipotent retinal progenitor cells (RPCs) and is
      known to play important roles in retinal development. In contrast, the proneural
      transcription factor Acheate scute-like 1 (ASCL1) is expressed transiently in a
      subset of RPCs, but is required for the production of most retinal neurons.
      Therefore, we asked whether the presence of VSX2 and ASCL1 could gauge neurogenic
      potential in 3D retinal cultures derived from human prenatal tissue or ES cells
      (hESCs). Short term prenatal 3D retinal cultures displayed multiple
      characteristics of human RPCs (hRPCs) found in situ, including robust expression
      of VSX2. Upon initiation of hRPC differentiation, there was a small increase in
      co-labeling of VSX2+ cells with ASCL1, along with a modest increase in the number
      of PKCalpha+ neurons. However, 3D prenatal retinal cultures lost expression of
      VSX2 and ASCL1 over time while concurrently becoming refractory to neuronal
      differentiation. Conversely, 3D optic vesicles derived from hESCs (hESC-OVs)
      maintained a robust VSX2+ hRPC population that could spontaneously co-express
      ASCL1 and generate photoreceptors and other retinal neurons for an extended
      period of time. These results show that VSX2 and ASCL1 can serve as markers for
      neurogenic potential in cultured hRPCs. Furthermore, unlike hESC-OVs, maintenance
      of 3D structure does not independently convey an advantage in the culture of
      prenatal hRPCs, further illustrating differences in the survival and
      differentiation requirements of hRPCs extracted from native tissue vs. those
      generated entirely in vitro. 

PMID- 26292214
TI  - Higher Trophic Levels Overwhelm Climate Change Impacts on Terrestrial Ecosystem
      Functioning.
AB  - Forest floor food webs play pivotal roles in carbon cycling, but they are rarely
      considered in models of carbon fluxes, including soil carbon dioxide emissions
      (respiration), under climatic warming. The indirect effects of invertebrates on
      heterotrophic (microbial and invertebrate) respiration through interactions with
      microbial communities are significant and will be altered by warming. However,
      the interactive effects of invertebrates and warming on heterotrophic respiration
      in the field are poorly understood. In this study we combined field and common
      garden laboratory approaches to examine relationships between warming, forest
      floor food web structure, and heterotrophic respiration. We found that soil
      animals can overwhelm the effects of warming (to 5 degrees Celsius above ambient)
      on heterotrophic respiration. In particular, the presence of higher trophic
      levels and burrowing detritivores strongly determined heterotrophic respiration
      rates in temperate forest soils. These effects were, however, context-dependent,
      with greater effects in a lower-latitude site. Without isolating and including
      the significant impact of invertebrates, climate models will be incomplete,
      hindering well-informed policy decisions. 

PMID- 26292213
TI  - HbA1c Test as a Tool in the Diagnosis of Gestational Diabetes Mellitus.
AB  - AIMS: Gestational diabetes mellitus (GDM) is a prevalent and potentially serious
      condition which may put both mothers and neonates at risk. The current
      recommendation for diagnosis is the oral glucose tolerance test (OGTT). This
      study aimed to determine the usefulness of HbA1c test as a diagnostic tool for
      GDM as compared to the traditional criteria based on the OGTT. METHODS: This was
      a diagnostic test accuracy study. We performed OGTT and HbA1c test in women
      attending prenatal visits at a tertiary hospital. GDM was defined according to
      WHO1999 or ADA/WHO 2013 criteria. ROC curve was used to evaluate the diagnostic
      performance of HbA1c. Sensitivity, specificity and likelihood ratios for
      different HbA1c cut-off points were calculated. RESULTS: Of the 262 women in the
      third trimester of gestation enrolled in the study, 86 (33%) were diagnosed with
      GDM. Only five of these women presented HbA1c >=48 mmol/mol (6.5%). This cut-off
      point presented 100% specificity but very low sensitivity (7%). Based on ROC
      curve, and considering OGTT as the reference criterion, HbA1c >=40 mmol/mol
      (5.8%) showed adequate specificity in diagnosing GDM (94.9%) but low sensitivity
      (26.4%). Unlike, HbA1c values of 31 mmol/mol (5.0%) presented adequate
      sensitivity (89.7%) but low specificity (32.6%) to detect GDM. For women with
      HbA1c >=40 mmol/mol (5.8%), the positive and negative likelihood ratios were 5.14
      (95%CI 2.49-10.63) and 0.78 (0.68-0.88), respectively. The post-test probability
      of GDM was about 40%, representing a 4.0-fold increase in the mean pre-test
      probability. This cut-off point could eliminate the need for the unpleasant and
      laborious OGTT tests in almost one third of cases, as 38% of patients with GDM
      may be diagnosable by HbA1c test alone. CONCLUSIONS: Our results show that
      combined HbA1c and OGTT measurements may be useful in diagnosing GDM.

PMID- 26292215
TI  - Hyperammonemia in Urinary Tract Infections.
AB  - OBJECTIVES: The present study investigated the incidence of hyperammonemia in
      urinary tract infections and explored the utility of urinary obstruction relief
      and antimicrobial administration to improve hyperammonemia. METHODS: This was an
      observational study. Subjects were patients who were diagnosed with urinary tract
      infection and hospitalized between June 2008 and June 2009. We measured plasma
      ammonia levels on admission in patients who were clinically diagnosed with
      urinary tract infection and hospitalized. We assessed each patient's level of
      consciousness on admission using the Glasgow Coma Scale (GCS) and performed urine
      and blood cultures. We also assessed hearing prior to hospitalization using the
      Eastern Cooperative Oncology Group performance status (ECOG-PS). In cases with
      high ammonia levels on admission, plasma ammonia and GCS were measured 24 hours
      and 5-7 days later. RESULTS: Sixty-seven candidates were enrolled; of these, 60
      cases (89.6%) with bacterial cell counts >=10(4) CFU/mL were studied. Five cases
      (8.3%) presented with high plasma ammonia levels. Cases with hyperammonemia were
      significantly more likely to present with low GCS scores and urinary retention
      rate. All five cases received antimicrobial therapy with an indwelling bladder
      catheter to relieve urinary retention. The case 5 patient died shortly after
      admission due to complicated aspiration pneumonia; in the remaining cases, plasma
      ammonia levels were rapidly normalized and the level of consciousness improved.
      CONCLUSIONS: The occurrence of hyperammonemia in urinary tract infections is not
      rare. The cause of hyperammonemia is urinary retention obstruction. Therefore,
      along with antimicrobial administration, relief of obstruction is important for
      the treatment of hyperammonemia caused by this mechanism.

PMID- 26292216
TI  - Functional equivalence of an evolutionarily conserved RNA binding module.
AB  - Members of the tristetraprolin (TTP) family of proteins participate in the
      regulation of mRNA turnover after initially binding to AU-rich elements in target
      mRNAs. Related proteins from most groups of eukaryotes contain a conserved tandem
      zinc finger (TZF) domain consisting of two closely spaced, similar CCCH zinc
      fingers that form the primary RNA binding domain. There is considerable sequence
      variation within the TZF domains from different family members within a single
      organism and from different organisms, raising questions about sequence-specific
      effects on RNA binding and decay promotion. We hypothesized that TZF domains from
      evolutionarily distant species are functionally interchangeable. The single
      family member expressed in the fission yeast Schizosaccharomyces pombe, Zfs1,
      promotes the turnover of several dozen transcripts, some of which are involved in
      cell-cell interactions. Using knockin techniques, we replaced the TZF domain of
      S. pombe Zfs1 with the equivalent domains from human TTP and the single family
      member proteins expressed in the silkworm Bombyx mori, the pathogenic yeast
      Candida guilliermondii, and the plant Chromolaena odorata. We found that the TZF
      domains from these widely disparate species could completely substitute for the
      native S. pombe TZF domain, as determined by measurement of target transcript
      levels and the flocculation phenotype characteristic of Zfs1 deletion.
      Recombinant TZF domain peptides from several of these species bound to an AU-rich
      RNA oligonucleotide with comparably high affinity. We conclude that the TZF
      domains from TTP family members in these evolutionarily widely divergent species
      are functionally interchangeable in mRNA binding and decay. 

PMID- 26292217
TI  - Galpha13 Switch Region 2 Binds to the Talin Head Domain and Activates
      alphaIIbbeta3 Integrin in Human Platelets.
AB  - Even though GPCR signaling in human platelets is directly involved in hemostasis
      and thrombus formation, the sequence of events by which G protein activation
      leads to alphaIIbbeta3 integrin activation (inside-out signaling) is not clearly
      defined. We previously demonstrated that a conformationally sensitive domain of
      one G protein, i.e. Galpha13 switch region 1 (Galpha13SR1), can directly
      participate in the platelet inside-out signaling process. Interestingly however,
      the dependence on Galpha13SR1 signaling was limited to PAR1 receptors, and did
      not involve signaling through other important platelet GPCRs. Based on the
      limited scope of this involvement, and the known importance of G13 in hemostasis
      and thrombosis, the present study examined whether signaling through another
      switch region of G13, i.e. Galpha13 switch region 2 (Galpha13SR2) may represent a
      more global mechanism of platelet activation. Using multiple experimental
      approaches, our results demonstrate that Galpha13SR2 forms a bi-molecular complex
      with the head domain of talin and thereby promotes beta3 integrin activation.
      Moreover, additional studies provided evidence that Galpha13SR2 is not
      constitutively associated with talin in unactivated platelets, but becomes bound
      to talin in response to elevated intraplatelet calcium levels. Collectively,
      these findings provide evidence for a novel paradigm of inside-out signaling in
      platelets, whereby beta3 integrin activation involves the direct binding of the
      talin head domain to the switch region 2 sequence of the Galpha13 subunit.

PMID- 26292218
TI  - Cleavage and cell adhesion properties of human epithelial cell adhesion molecule
      (HEPCAM).
AB  - Human epithelial cell adhesion molecule (HEPCAM) is a tumor-associated antigen
      frequently expressed in carcinomas, which promotes proliferation after regulated
      intramembrane proteolysis. Here, we describe extracellular shedding of HEPCAM at
      two alpha-sites through a disintegrin and metalloprotease (ADAM) and at one beta
      site through BACE1. Transmembrane cleavage by gamma-secretase occurs at three
      gamma-sites to generate extracellular Abeta-like fragments and at two epsilon
      sites to release human EPCAM intracellular domain HEPICD, which is efficiently
      degraded by the proteasome. Mapping of cleavage sites onto three-dimensional
      structures of HEPEX cis-dimer predicted conditional availability of alpha- and
      beta-sites. Endocytosis of HEPCAM warrants acidification in cytoplasmic vesicles
      to dissociate protein cis-dimers required for cleavage by BACE1 at low pH values.
      Intramembrane cleavage sites are accessible and not part of the structurally
      important transmembrane helix dimer crossing region. Surprisingly, neither
      chemical inhibition of cleavage nor cellular knock-out of HEPCAM using CRISPR
      Cas9 technology impacted the adhesion of carcinoma cell lines. Hence, a direct
      function of HEPCAM as an adhesion molecule in carcinoma cells is not supported
      and appears to be questionable. 

PMID- 26292219
TI  - Transcription Factor Hepatocyte Nuclear Factor-1beta (HNF-1beta) Regulates
      MicroRNA-200 Expression through a Long Noncoding RNA.
AB  - The transcription factor hepatocyte nuclear factor-1beta (HNF-1beta) regulates
      tissue-specific gene expression in the kidney and other epithelial organs.
      Mutations of HNF-1beta produce kidney cysts, and previous studies have shown that
      HNF-1beta regulates the transcription of cystic disease genes, including Pkd2 and
      Pkhd1. Here, we combined chromatin immunoprecipitation and next-generation
      sequencing (ChIP-Seq) with microarray analysis to identify microRNAs (miRNAs)
      that are directly regulated by HNF-1beta in renal epithelial cells. These studies
      identified members of the epithelial-specific miR-200 family (miR-200b/200a/429)
      as novel transcriptional targets of HNF-1beta. HNF-1beta binds to two
      evolutionarily conserved sites located 28 kb upstream to miR-200b. Luciferase
      reporter assays showed that the HNF-1beta binding sites were located within a
      promoter that was active in renal epithelial cells. Mutations of the HNF-1beta
      binding sites abolished promoter activity. RT-PCR analysis revealed that a long
      noncoding RNA (lncRNA) is transcribed from the promoter and encodes the miR-200
      cluster. Inhibition of the lncRNA with siRNAs decreased the levels of miR-200 but
      did not affect expression of the Ttll10 host gene. The expression of the lncRNA
      and miR-200 was decreased in kidneys from HNF-1beta knock-out mice and renal
      epithelial cells expressing dominant-negative mutant HNF-1beta. The expression of
      miR-200 targets, Zeb2 and Pkd1, was increased in HNF-1beta knock-out kidneys and
      in cells expressing mutant HNF-1beta. Overexpression of miR-200 decreased the
      expression of Zeb2 and Pkd1 in HNF-1beta mutant cells. These studies reveal a
      novel pathway whereby HNF-1beta directly contributes to the control of miRNAs
      that are involved in epithelial-mesenchymal transition and cystic kidney disease.

PMID- 26292220
TI  - Cellular interaction and cytotoxicity of the iowa mutation of apolipoprotein A-I
      (ApoA-IIowa) amyloid mediated by sulfate moieties of heparan sulfate.
AB  - The single amino acid mutation G26R in human apolipoprotein A-I (apoA-I) is
      associated with familial amyloid polyneuropathy III. ApoA-I carrying this
      mutation (apoA-IIowa) forms amyloid fibrils in vitro. Heparan sulfate (HS) is a
      glycosaminoglycan that is abundant at the cell surface and in the extracellular
      matrix. Although HS and its highly sulfated domains are involved in aggregation
      of amyloid-beta and accumulate in cerebral amyloid plaques of patients with
      Alzheimer disease and mouse models of this disease, the role of HS in familial
      amyloid polyneuropathy III has never been addressed. Here, we used cell models to
      investigate the possible role of HS in the cytotoxicity of apoA-IIowa amyloid.
      Wild-type CHO cells, but not pgsD-677 cells, an HS-deficient CHO mutant,
      demonstrated uptake of apoA-IIowa amyloid after incubation with the amyloid.
      Addition of sulfated glycosaminoglycans to culture media prevented interaction
      with and cytotoxicity of apoA-IIowa amyloid to CHO cells. Elimination of cell
      surface HS or inhibition of HS sulfation with chemical reagents interfered with
      interaction of apoA-IIowa amyloid with CHO cells. We also found that cellular
      interaction and cytotoxicity of apoA-IIowa amyloid were significantly attenuated
      in CHO cells that stably expressed the human extracellular endoglucosamine 6
      sulfatases HSulf-1 and HSulf-2. Our results thus suggest that cell surface HS
      mediates cytotoxicity of apoA-IIowa amyloid and that enzymatic remodeling of HS
      mitigates the cytotoxicity. 

PMID- 26292221
TI  - Pomalidomide alone or in combination with dexamethasone in Japanese patients with
      refractory or relapsed and refractory multiple myeloma.
AB  - This phase 1, open-label, dose-escalation study investigated the tolerated dose
      (recommended dose), safety, efficacy, and pharmacokinetics of pomalidomide alone
      or pomalidomide plus low-dose dexamethasone in Japanese patients with refractory
      or relapsed and refractory multiple myeloma. Twelve patients were enrolled.
      Patients received pomalidomide 2 mg (Cohort 1) or 4 mg (Cohort 2) orally on day 1
      and days 3-21 of a 28-day cycle. The tolerated dose of pomalidomide was
      determined to be 4 mg given on days 1-21 of a 28-day cycle. Efficacy outcomes
      with pomalidomide plus low-dose dexamethasone were consistent with those of
      previous studies. Responses (partial response or better) were achieved by three
      patients (25%; 1 [17%] in Cohort 1 and 2 [33%] in Cohort 2), and the median time
      to response was 6.4 months overall (9.0 months for Cohort 1 and 4.2 months for
      Cohort 2). The median progression-free survival was 5.5 months overall (5.1
      months for Cohort 1 and not reached for Cohort 2). The most frequently occurring
      grade >=3 adverse events were neutropenia (67%), anemia (25%), lymphopenia (25%),
      and pneumonia (25%), consistent with previous studies of pomalidomide plus low
      dose dexamethasone in refractory or relapsed and refractory multiple myeloma.
      Further investigation of pomalidomide is recommended for Japanese patients with
      refractory or relapsed and refractory multiple myeloma. This study was registered
      with ClinicalTrials.gov (NCT01568294). 

PMID- 26292222
TI  - Cocos nucifera (L.) (Arecaceae): A phytochemical and pharmacological review.
AB  - Cocos nucifera (L.) (Arecaceae) is commonly called the "coconut tree" and is the
      most naturally widespread fruit plant on Earth. Throughout history, humans have
      used medicinal plants therapeutically, and minerals, plants, and animals have
      traditionally been the main sources of drugs. The constituents of C. nucifera
      have some biological effects, such as antihelminthic, anti-inflammatory,
      antinociceptive, antioxidant, antifungal, antimicrobial, and antitumor
      activities. Our objective in the present study was to review the phytochemical
      profile, pharmacological activities, and toxicology of C. nucifera to guide
      future preclinical and clinical studies using this plant. This systematic review
      consisted of searches performed using scientific databases such as Scopus,
      Science Direct, PubMed, SciVerse, and Scientific Electronic Library Online. Some
      uses of the plant were partially confirmed by previous studies demonstrating
      analgesic, antiarthritic, antibacterial, antipyretic, antihelminthic,
      antidiarrheal, and hypoglycemic activities. In addition, other properties such as
      antihypertensive, anti-inflammatory, antimicrobial, antioxidant,
      cardioprotective, antiseizure, cytotoxicity, hepatoprotective, vasodilation,
      nephroprotective, and anti-osteoporosis effects were also reported. Because each
      part of C. nucifera has different constituents, the pharmacological effects of
      the plant vary according to the part of the plant evaluated. 

PMID- 26292223
TI  - Influence of transcutaneous electrical stimulation on heterotopic ossification:
      an experimental study in Wistar rats.
AB  - Heterotopic ossification (HO) is a metaplastic biological process in which there
      is newly formed bone in soft tissues, resulting in joint mobility deficit and
      pain. Different treatment modalities have been tried to prevent HO development,
      but there is no consensus on a therapeutic approach. Since electrical stimulation
      is a widely used resource in physiotherapy practice to stimulate joint mobility,
      with analgesic and anti-inflammatory effects, its usefulness for HO treatment was
      investigated. We aimed to identify the influence of electrical stimulation on
      induced HO in Wistar rats. Thirty-six male rats (350-390 g) were used, and all
      animals were anesthetized for blood sampling before HO induction, to quantify the
      serum alkaline phosphatase. HO induction was performed by bone marrow
      implantation in both quadriceps of the animals, which were then divided into 3
      groups: control (CG), transcutaneous electrical nerve stimulation (TENS) group
      (TG), and functional electrical stimulation (FES) group (FG) with 12 rats each.
      All animals were anesthetized and electrically stimulated twice per week, for 35
      days from induction day. After this period, another blood sample was collected
      and quadriceps muscles were bilaterally removed for histological and calcium
      analysis and the rats were killed. Calcium levels in muscles showed significantly
      lower results when comparing TG and FG (P<0.001) and between TG and CG (P<0.001).
      Qualitative histological analyses confirmed 100% HO in FG and CG, while in TG the
      HO was detected in 54.5% of the animals. The effects of the muscle contractions
      caused by FES increased HO, while anti-inflammatory effects of TENS reduced HO. 

PMID- 26292224
TI  - Evolutionary Consequence of a Trade-Off between Growth and Maintenance along with
      Ribosomal Damages.
AB  - Microorganisms in nature are constantly subjected to a limited availability of
      resources and experience repeated starvation and nutrition. Therefore, microbial
      life may evolve for both growth fitness and sustainability. By contrast,
      experimental evolution, as a powerful approach to investigate microbial
      evolutionary strategies, often targets the increased growth fitness in
      controlled, steady-state conditions. Here, we address evolutionary changes
      balanced between growth and maintenance while taking nutritional fluctuations
      into account. We performed a 290-day-long evolution experiment with a histidine
      requiring Escherichia coli strain that encountered repeated histidine-rich and
      histidine-starved conditions. The cells that experienced seven rounds of
      starvation and re-feed grew more sustainably under prolonged starvation but
      dramatically lost growth fitness under rich conditions. The improved
      sustainability arose from the evolved capability to use a trace amount of
      histidine for cell propagation. The reduced growth rate was attributed to
      mutations genetically disturbing the translation machinery, that is, the
      ribosome, ultimately slowing protein translation. This study provides the
      experimental demonstration of slow growth accompanied by an enhanced affinity to
      resources as an evolutionary adaptation to oscillated environments and verifies
      that it is possible to evolve for reduced growth fitness. Growth economics
      favored for population increase under extreme resource limitations is most likely
      a common survival strategy adopted by natural microbes. 

PMID- 26292225
TI  - Validation of Cut-Points for Evaluating the Intensity of Physical Activity with
      Accelerometry-Based Mean Amplitude Deviation (MAD).
AB  - PURPOSE: Our recent study of three accelerometer brands in various ambulatory
      activities showed that the mean amplitude deviation (MAD) of the resultant
      acceleration signal performed best in separating different intensity levels and
      provided excellent agreement between the three devices. The objective of this
      study was to derive a regression model that estimates oxygen consumption (VO2)
      from MAD values and validate the MAD-based cut-points for light, moderate and
      vigorous locomotion against VO2 within a wide range of speeds. METHODS: 29
      participants performed a pace-conducted non-stop test on a 200 m long indoor
      track. The initial speed was 0.6 m/s and it was increased by 0.4 m/s every 2.5
      minutes until volitional exhaustion. The participants could freely decide whether
      they preferred to walk or run. During the test they carried a hip-mounted tri
      axial accelerometer and mobile metabolic analyzer. The MAD was calculated from
      the raw acceleration data and compared to directly measured incident VO2. Cut
      point between light and moderate activity was set to 3.0 metabolic equivalent
      (MET, 1 MET = 3.5 ml . kg-1 . min-1) and between moderate and vigorous activity
      to 6.0 MET as per standard use. RESULTS: The MAD and VO2 showed a very strong
      association. Within individuals, the range of r values was from 0.927 to 0.991
      providing the mean r = 0.969. The optimal MAD cut-point for 3.0 MET was 91 mg
      (milligravity) and 414 mg for 6.0 MET. CONCLUSION: The present study showed that
      the MAD is a valid method in terms of the VO2 within a wide range of ambulatory
      activities from slow walking to fast running. Being a device-independent trait,
      the MAD facilitates directly comparable, accurate results on the intensity of
      physical activity with all accelerometers providing tri-axial raw data.

PMID- 26292227
TI  - In Situ NMR Study on the Interaction between LiBH4-Ca(BH4)2 and Mesoporous
      Scaffolds.
AB  - We discuss the use of nuclear magnetic resonance (NMR) spectroscopy to
      investigate the physical state of the eutectic composition of LiBH4-Ca(BH4)2 (LC)
      infiltrated into mesoporous scaffolds and the interface effect of various
      scaffolds. Eutectic melting and the melt infiltration of mixed borohydrides were
      observed through in situ NMR. In situ and ex situ NMR results for LC mixed with
      mesoporous scaffolds indicate that LiBH4 and Ca(BH4)2 exist as an amorphous
      mixture inside of the pores after infiltration. Surprisingly, the confinement of
      the eutectic LC mixture within the mesopores is initiated below the melting
      temperature, which indicates a certain interaction between the borohydrides and
      the mesoporous scaffolds. The confined borohydrides remain inside of the pores
      after cooling. These phenomena were not observed in microporous or nonporous
      materials, and this observation highlights the importance of the pore structure
      of the scaffolds. Such surface interactions may be associated with a faster
      dehydrogenation of the nanoconfined borohydrides. 

PMID- 26292228
TI  - Electrochemical Supercapacitor Electrodes from Sponge-like Graphene
      Nanoarchitectures with Ultrahigh Power Density.
AB  - We employed a microwave synthesis process of cobalt phthalocyanine molecules
      templated by acid-functionalized multiwalled carbon nanotubes to create three
      dimensional sponge-like graphene nanoarchitectures suited for ionic liquid-based
      electrochemical capacitor electrodes that operate at very high scan rates. The
      sequential "bottom-up" molecular synthesis and subsequent carbonization process
      took less than 20 min to complete. The 3D nanoarchitectures are able to deliver
      an energy density of 7.1 W.h kg(-1) even at an extra high power density of 48 000
      W kg(-1). In addition, the ionic liquid supercapacitor based on this material
      works very well at room temperature due to its fully opened structures, which is
      ideal for the high-power energy application requiring more tolerance to
      temperature variation. Moreover, the structures are stable in both ionic liquids
      and 1 M H2SO4, retaining 90 and 98% capacitance after 10 000 cycles,
      respectively. 

PMID- 26292226
TI  - Demographic History of Indigenous Populations in Mesoamerica Based on mtDNA
      Sequence Data.
AB  - The genetic characterization of Native American groups provides insights into
      their history and demographic events. We sequenced the mitochondrial D-loop
      region (control region) of 520 samples from eight Mexican indigenous groups. In
      addition to an analysis of the genetic diversity, structure and genetic
      relationship between 28 Native American populations, we applied Bayesian skyline
      methodology for a deeper insight into the history of Mesoamerica. AMOVA tests
      applying cultural, linguistic and geographic criteria were performed. MDS plots
      showed a central cluster of Oaxaca and Maya populations, whereas those from the
      North and West were located on the periphery. Demographic reconstruction
      indicates higher values of the effective number of breeding females (Nef) in
      Central Mesoamerica during the Preclassic period, whereas this pattern moves
      toward the Classic period for groups in the North and West. Conversely, Nef
      minimum values are distributed either in the Lithic period (i.e. founder effects)
      or in recent periods (i.e. population declines). The Mesomerican regions showed
      differences in population fluctuation as indicated by the maximum Inter
      Generational Rate (IGRmax): i) Center-South from the lithic period until the
      Preclassic; ii) West from the beginning of the Preclassic period until early
      Classic; iii) North characterized by a wide range of temporal variation from the
      Lithic to the Preclassic. Our findings are consistent with the genetic variations
      observed between central, South and Southeast Mesoamerica and the North-West
      region that are related to differences in genetic drift, structure, and temporal
      survival strategies (agriculture versus hunter-gathering, respectively).
      Interestingly, although the European contact had a major negative demographic
      impact, we detect a previous decline in Mesoamerica that had begun a few hundred
      years before. 

PMID- 26292229
TI  - Tuning Magnetism and Electronic Phase Transitions by Strain and Electric Field in
      Zigzag MoS2 Nanoribbons.
AB  - Effective modulation of physical properties via external control may open various
      potential nanoelectronic applications of single-layer MoS2 nanoribbons (MoS2NRs).
      We show by first-principles calculations that the magnetic and electronic
      properties of zigzag MoS2NRs exhibit sensitive response to applied strain and
      electric field. Tensile strain in the zigzag direction produces reversible
      modulation of magnetic moments and electronic phase transitions among metallic,
      half-metallic, and semiconducting states, which stem from the energy-level shifts
      induced by an internal electric polarization and the competing covalent/ionic
      interactions. A simultaneously applied electric field further enhances or
      suppresses the strain-induced modulations depending on the direction of the
      electric field relative to the internal polarization. These findings suggest a
      robust and efficient approach to modulating the properties of MoS2NRs by a
      combination of strain engineering and electric field tuning. 

PMID- 26292230
TI  - Homogeneous Nucleation of Methane Hydrate in Microsecond Molecular Dynamics
      Simulations.
AB  - We report atomistically detailed molecular dynamics simulations of homogeneous
      nucleation of methane hydrate in bulk aqueous phase in the absence of any
      interface. Subcritical clusters of water and methane molecules are formed in the
      initial segment of the simulations, which then aggregate to give the critical
      hydrate nucleus. This occurs over time scales of several hundred nanoseconds,
      indicating that the formation and aggregation of subcritical clusters can
      contribute significantly to the overall rate of hydrate nucleation. The clusters
      have elements of sI hydrate structure, such as 5(12) and 5(12)6(2) cages as well
      as other uncommon 5(12)6(3) and 5(12)6(4) cages, but do not possess long-range
      order. Clusters are dynamic in nature and undergo continuous structural
      rearrangements. 

PMID- 26292231
TI  - Unifying the 2e(-) and 4e(-) Reduction of Oxygen on Metal Surfaces.
AB  - Understanding trends in selectivity is of paramount importance for multi-electron
      electrochemical reactions. The goal of this work is to address the issue of 2e(-)
      versus 4e(-) reduction of oxygen on metal surfaces. Using a detailed
      thermodynamic analysis based on density functional theory calculations, we show
      that to a first approximation an activity descriptor, DeltaGOH*, the free energy
      of adsorbed OH*, can be used to describe trends for the 2e(-) and 4e(-) reduction
      of oxygen. While the weak binding of OOH* on Au(111) makes it an unsuitable
      catalyst for the 4e(-) reduction, this weak binding is optimal for the 2e(-)
      reduction to H2O2. We find quite a remarkable agreement between the predictions
      of the model and experimental results spanning nearly 30 years. 

PMID- 26292232
TI  - Intensity Dependent Femtosecond Dynamics in a PBDTTPD-Based Solar Cell Material.
AB  - PBDTTPD is a conjugated polymer with high power conversion efficiency if used in
      organic solar cells together with fullerene derivatives. We have investigated for
      the first time the excited state dynamics of pristine PBDTTPD thin film as well
      as the ultrafast evolution of charge carriers in PBDTTPD:PCBM bulk heterojunction
      blend using femtosecond transient absorption spectroscopy. In the latter, charges
      appear within the time resolution of the experiment (<100 fs), but clean spectral
      signatures allowed to directly follow slower ~1 ps charge separation. Only the
      slower quenching component competes with exciton-exciton and exciton-charge
      annihilation, leading to a reduced yield of charge carriers at high laser
      fluence. Our excellent measuring sensitivity made it possible to reduce pump
      power to a point where annihilation is quasi suppressed. In this case >80% of
      charges survive after 1 ns; the rest recombines (most probably geminately) on the
      200 ps time scale. 

PMID- 26292233
TI  - H + D2 Reaction Dynamics in the Limit of Low Product Recoil Energy.
AB  - Both experiment and theory recently showed that the H + D2(v = 0, j = 0) -> HD(v'
      = 4, j') + D reactions at a collision energy of 1.97 eV display a seemingly
      anomalous HD product angular distribution that moves in the backward direction as
      the value of j' increases and the corresponding energy available for product
      recoil decreases. This behavior was attributed to the presence of a centrifugal
      barrier along the reaction path. Here, we show, using fully quantum mechanical
      calculations, that for low recoil energies, the collision mechanism is nearly
      independent of the HD internal state and the HD product becomes aligned, with its
      rotational angular momentum j' pointing perpendicular to the recoil momentum k'.
      As the kinetic energy to overcome this barrier becomes limited, the three atoms
      adopt a nearly collinear configuration in the transition-state region to permit
      reaction, which strongly polarizes the resulting HD product. These results are
      expected to be general for any chemical reaction in the low recoil energy limit. 

PMID- 26292234
TI  - Dynamics of Dangling Bonds of Water Molecules in pharaonis Halorhodopsin during
      Chloride Ion Transportation.
AB  - Ion transportation via the chloride ion pump protein pharaonis halorhodopsin
      (pHR) occurs through the sequential formation of several intermediates during a
      photocyclic reaction. Although the structural details of each intermediate state
      have been studied, the role of water molecules in the translocation of chloride
      ions inside of the protein at physiological temperatures remains unclear. To
      analyze the structural dynamics of water inside of the protein, we performed time
      resolved Fourier transform infrared (FTIR) spectroscopy under H2O or H2(18)O
      hydration and successfully assigned water O-H stretching bands. We found that a
      dangling water band at 3626 cm(-1) in pHR disappears in the L1 and L2 states. On
      the other hand, relatively intense positive bands at 3605 and 3608 cm(-1) emerged
      upon the formation of the X(N) and O states, respectively, suggesting that the
      chloride transportation is accompanied by dynamic rearrangement of the hydrogen
      bonding network of the internal water molecules in pHR. 

PMID- 26292235
TI  - Acetone-Assisted Oxygen Vacancy Diffusion on TiO2(110).
AB  - We have studied the dynamic relationship between acetone and bridge-bonded oxygen
      (Ob) vacancy (VO) defect sites on the TiO2(110)-1 * 1 surface using scanning
      tunneling microscopy (STM) and density function theory (DFT) calculations. We
      report an adsorbate-assisted VO diffusion mechanism. The STM images taken at 300
      K show that acetone preferably adsorbs on the VO site and is mobile. The
      sequential isothermal STM images directly show that the mobile acetone
      effectively migrates the position of VO by a combination of two acetone diffusion
      channels: one is the diffusion along the Ob row and moving as an alkyl group,
      which heals the initial VO; another is the diffusion from the Ob row to the five
      coordinated Ti(4+) row and then moving along the Ti(4+) row as an acetone, which
      leaves a VO behind. The calculated acetone diffusion barriers for the two
      channels are comparable and agree with experimental results. 

PMID- 26292236
TI  - Improved CO Adsorption Energies, Site Preferences, and Surface Formation Energies
      from a Meta-Generalized Gradient Approximation Exchange-Correlation Functional,
      M06-L.
AB  - A notorious failing of approximate exchange-correlation functionals when applied
      to problems involving catalysis has been the inability of most local functionals
      to predict the correct adsorption site for CO on metal surfaces or to
      simultaneously predict accurate surface formation energies and adsorption
      energies for transition metals. By adding the kinetic energy density tau to the
      density functional, the revTPSS density functional was shown recently to achieve
      a balanced description of surface energies and adsorption energies. Here, we show
      that the older M06-L density functional, also containing tau, provides improved
      surface formation energies and CO adsorption energies over revTPSS for five
      transition metals and correctly predicted the on-top/hollow site adsorption
      preferences for four of the five metals, which was not achieved by most other
      local functionals. Because M06-L was entirely designed on the basis of atomic and
      molecular energies, its very good performance is a confirmation of the
      reasonableness of its functional form. Two GGA functionals with an expansion in
      the reduced gradient that is correct through second order, namely, SOGGA and
      SOGGA11, were also tested and found to produce the best surface formation
      energies of all tested GGA functionals, although they significantly overestimate
      the adsorption energies. 

PMID- 26292237
TI  - Prediction of Absolute Hydroxyl pKa Values for 3-Hydroxypyridin-4-ones.
AB  - pKa values have been calculated for a series of 3-hydroxypyridin-4-one (HPO)
      chelators in aqueous solution using coordination constrained ab initio molecular
      dynamics (AIMD) in combination with thermodynamic integration. This dynamics
      based methodology in which the solvent is treated explicitly at the ab initio
      level has been compared with more commonly used simple, static, approaches.
      Comparison with experimental numbers has confirmed that the AIMD-based approach
      predicts the correct trend in the pKa values and produces the lowest average
      error (~0.3 pKa units). The corresponding pKa predictions made via static quantum
      mechanical calculations overestimate the pKa values by 0.3-7 pKa units, with the
      extent of error dependent on the choice of thermodynamic cycle employed. The use
      of simple quantitative structure property relationship methods gives prediction
      errors of 0.3-1 pKa units, with some values overestimated and some
      underestimated. Beyond merely calculating pKa values, the AIMD simulations
      provide valuable additional insight into the atomistic details of the proton
      transfer mechanism and the solvation structure and dynamics at all stages of the
      reaction. For all HPOs studied, it is seen that proton transfer takes place along
      a chain of three H2O molecules, although direct hydrogen bonds are seen to form
      transiently. Analysis of the solvation structure before and after the proton
      transfer event using radial pair distribution functions and integrated number
      densities suggests that the trends in the pKa values correlate with the strength
      of the hydrogen bond and the average number of solvent molecules in the vicinity
      of the donor oxygen. 

PMID- 26292238
TI  - Image Charge Effects on the Formation of Pickering Emulsions.
AB  - Vigorous mixing of an aqueous particle dispersion with oil usually produces a
      particle-stabilized emulsion (a "Pickering emulsion"), the longevity of which
      depends on the particles' wetting properties. A known exception occurs when
      particles fail to adsorb to the oil-water interface created during mixing because
      of a strong repulsion between charges on the particle surface and similar charges
      on the oil-water interface; in this case, no Pickering emulsion is formed. Here,
      we present experimental evidence that the rarely considered electrostatic image
      force can cause a much bigger hindrance to particle adsorption and prevent the
      formation of Pickering emulsions even when the particle interaction with the
      interface charge is attractive. A simple theoretical estimate confirms the
      observed magnitude of this effect and points at an important limitation of
      Pickering emulsification, a technology with widespread industrial applications
      and increasing popularity in materials research and development. 

PMID- 26292239
TI  - Two-Photon-Induced Selective Decarboxylation of Aspartic Acids D85 and D212 in
      Bacteriorhodopsin.
AB  - The interest in microbial opsins stems from their photophysical properties, which
      are superior to most organic dyes. Microbial rhodopsins like bacteriorhodopsin
      (BR) from Halobacterium salinarum have an astonishingly high cross-section for
      two-photon-absorption (TPA), which is of great interest for technological
      applications such as data storage. Irradiation of BR with intense laser pulses at
      532 nm leads to formation of a bathochromic photoproduct, which is further
      converted to a photochemical species absorbing in the UV range. As demonstrated
      earlier, the photochemical conversions are induced by resonant TPA. However, the
      molecular basis of these conversions remained unresolved. In this work we use
      mass spectroscopy to demonstrate that TPA of BR leads to selective
      decarboxylation of two aspartic acids in the vicinity of the retinal chromphore.
      These photochemical conversions are the basis of permanent two-photon data
      storage in BR and are of critical importance for application of microbial opsins
      in optogenetics. 

PMID- 26292240
TI  - Controlling the Excited-State Reaction Dynamics of a Photochromic Molecular
      Switch with Sequential Two-Photon Excitation.
AB  - Sequential two-photon excitation increases the cycloreversion yield of a
      diarylethene-type photochromic molecular switch compared with one-photon
      excitation. This letter shows for the first time that an optimal delay of ~5 ps
      between primary and secondary excitation events gives the largest enhancement of
      the ring-closing reaction. Pump-probe (PP) and pump-repump-probe (PReP)
      measurements also provide detailed new information about the excited-state
      dynamics. The initially excited molecule must first cross a barrier on the
      excited-state potential energy surface before secondary excitation enhances the
      reaction. The PReP experiments demonstrate that the reaction path of a
      photochromic molecular switch can be selectively controlled through judicious use
      of time-delayed femtosecond laser pulses. 

PMID- 26292241
TI  - Origin of Vibrational Spectroscopic Response at Ice Surface.
AB  - Since the basal plane surface of ice was first observed by sum frequency
      generation, an extraordinarily intense band for the hydrogen(H)-bonded OH
      stretching vibration has been a matter of debate. We elucidate the remarkable
      spectral feature of the ice surface by quantum mechanics/molecular mechanics
      calculations. The intense H-bonded band is originated mostly from the "bilayer
      stitching" modes of a few surface bilayers, through significant intermolecular
      charge transfer. The mechanism of enhanced signal is sensitive to the order of
      the tetrahedral ice structure, as the charge transfer is coupled to the
      vibrational delocalization. 

PMID- 26292242
TI  - Resonance Charges to Encode Selection Rules in Inelastic Electron Tunneling
      Spectroscopy.
AB  - From extensive simulations of a set of covalently grafted phenyl derivatives onto
      Cu(111), we derive a simplistic rule that selectively predicts the onset of
      stretching vibrations in inelastic electron tunneling spectroscopy (IETS) with
      the scanning tunneling microscope. Indeed the rise (extinction) of the highest
      frequency modes is found to correlate to the accumulation (depletion) of pi
      electron density at the metal-organic contact point. This pi electron density can
      be fine-tuned by the usage of (de) activating aromatic substituent at different
      ring positions. This finding provides a simple analysis tool that can be used to
      reveal structural characteristics on the atomic scale by IETS. 

PMID- 26292243
TI  - From Conventional to Phase-Sensitive Vibrational Sum Frequency Generation
      Spectroscopy: Probing Water Organization at Aqueous Interfaces.
AB  - Elucidation of water organization at aqueous interfaces has remained a
      challenging problem. Conventional vibrational sum frequency generation (VSFG)
      spectroscopy and its most recent extension, phase-sensitive VSFG (PS-VSFG), have
      emerged as powerful experimental methods for unraveling structural information at
      various aqueous interfaces. In this Perspective, we briefly describe the two
      possible VSFG detection modes, and we point out features that make these methods
      highly suited to address questions about water organization at air/aqueous
      interfaces. Several important aqueous interfacial systems are discussed to
      illustrate the versatility of these methods. Remaining challenges and exciting
      prospective directions are also presented. 

PMID- 26292244
TI  - DNA Bending through Roll Angles Is Independent of Adjacent Base Pairs.
AB  - We have studied DNA bending for a wide range of DNA sequences by two-dimensional
      adaptive umbrella sampling simulations on adjacent roll angles. Calculated free
      energy surfaces are largely additive and can be well approximated by the sum of
      the one-dimensional free energy surfaces. Cooperativity between adjacent roll
      angles was found to be negligible: less than 1.0 kcal/mol and a small fraction of
      the overall bending energy. Our calculations validate the assumptions underlying
      many popular coarse-grained models for DNA bending, and demonstrate their
      theoretical validity for investigating DNA bending. 

PMID- 26292245
TI  - Hydrogen-Bond Dynamics in a Protic Ionic Liquid: Evidence of Large-Angle Jumps.
AB  - We study the molecular rotation of the protic room-temperature ionic liquid
      ethylammonium nitrate with dielectric relaxation spectroscopy and femtosecond
      infrared spectroscopy (fs-IR) of the ammonium N-H vibrations. The results suggest
      that the rotation of ethylammonium ion takes place via large angular jumps. Such
      nondiffusive reorientational dynamics is unique to strongly hydrogen-bonded
      liquids such as water and indicates that the intermolecular interaction is highly
      directional in this class of ionic liquids. 

PMID- 26292246
TI  - Electron-Lattice Coupling in Armchair Graphene Nanoribbons.
AB  - We report the effects of electron-lattice coupling on the charge density
      distribution study of armchair graphene nanoribbons (GNRs). Here, we perform a
      theoretical investigation explaining the unexpected electronic density states
      observed experimentally. By means of a tight-binding approach with electron
      lattice coupling, we obtained the same characteristic pattern of charge density
      along the C-C bonds suggested by both scanning tunneling and transmission
      electron microscopic measurements. Our results suggest electronic localized
      states whose sizes are dependent on the GNR width. We also show that our model
      rescues the quasi-particle charge-transport mechanism in GNRs. The remarkable
      agreement with experimental evidence allows us to conclude that our model could
      be, in many aspects, a fundamental tool when it comes to the phenomenological
      understanding of the charge behavior in this kind of system. 

PMID- 26292247
TI  - Limitations in Rechargeability of Li-O2 Batteries and Possible Origins.
AB  - Quantitative differential electrochemical mass spectrometry (DEMS) is used to
      measure the Coulombic efficiency of discharge and charge [(e(-)/O2)dis and (e(
      )/O2)chg] and chemical rechargeability (characterized by the O2 recovery
      efficiency, OER/ORR) for Li-O2 electrochemistry in a variety of nonaqueous
      electrolytes. We find that none of the electrolytes studied are truly
      rechargeable, with OER/ORR <90% for all. Our findings emphasize that neither the
      overpotential for recharge nor capacity fade during cycling are adequate to
      assess rechargeability. Coulometry has to be coupled to quantitative measurements
      of the chemistry to measure the rechargeability truly. We show that
      rechargeability in the various electrolytes is limited both by chemical reaction
      of Li2O2 with the solvent and by electrochemical oxidation reactions during
      charging at potentials below the onset of electrolyte oxidation on an inert
      electrode. Possible mechanisms are suggested for electrolyte decomposition, which
      taken together, impose stringent conditions on the liquid electrolyte in Li-O2
      batteries. 

PMID- 26292248
TI  - Filled and Empty Orbital Interactions in a Planar Covalent Organic Framework on
      Graphene.
AB  - The electronic characteristics of a planar covalent organic framework (COF) on
      graphene are investigated by means of dispersion-corrected density functional
      theory. The aromatic central molecule of the COF acts as an electron donor to
      graphene, while the linker of the COF acts as an electron acceptor. The concerted
      interaction between the filled orbitals of the central molecule and empty
      orbitals of the linker promotes the formation of planar COF networks on graphene.
      The calculation results are in very good agreement with experimental findings of
      an ordered hexagonal and square COF planar on graphene, which sheds light on the
      supermolecular assembly mechanism. 

PMID- 26292249
TI  - High-Temperature Chemistry in Solid Oxide Fuel Cells: In Situ Optical Studies.
AB  - Solid oxide fuels cells (SOFCs) are promising devices for versatile and efficient
      power generation with fuel flexibility, but their viability is contingent upon
      understanding chemical and material processes to improve their performance and
      durability. Newly developed in situ optical methods provide new insight into how
      carbon deposition varies with different hydrocarbon and alcohol fuels and depends
      on operating conditions. Some findings, such as heavier hydrocarbon fuels forming
      more carbon than lighter fuels, are expected, but other discoveries are
      surprising. For example, methanol shows a greater tendency to form carbon
      deposits than methane at temperatures below 800  degrees C, and kinetically
      controlled steam reforming with ethanol at high temperatures (~800  degrees C) is
      less detrimental to SOFC performance than operating the device with dry methanol
      as the fuel. In situ optical techniques will continue to provide the chemical
      information and mechanistic insight that is critical for SOFCs to become a viable
      energy conversion technology. 

PMID- 26292250
TI  - First-Principles Identification of Iodine Exchange Mechanism in Iodide Ionic
      Liquid.
AB  - We investigated the microscopic mechanism of ion transport in iodide ionic
      liquid, using first-principles calculations. We show that the desorption barrier
      of polyiodides (I3(-) or I5(-)) from the cation is in a similar energy range as
      or higher than the barrier for the bond dissociation and ensued desorption of
      neutral iodine (I2). This suggests that, instead of the physical diffusion of
      such a negatively charged multiatomic species, the exchange of neutral iodine
      (I2) between the polyiodides can be an easier channel for the movement of
      polyiodide. For the transport of the monoiodide anion (I(-)), we suggest the
      contribution of the Grotthuss-type ion exchange through the intermediately formed
      even-member anion (I2n(-)), in addition to drift and diffusion. As a result, we
      suggest that, instead of the commonly cited diffusion of the triiodide/iodide
      (I3(-)/I(-)) redox couple, the exchange of neutral iodine (I2) and the Grotthuss
      type transport (I(-)) constitute the dominant ion transport mechanism. 

PMID- 26292251
TI  - Optical Interrogation of Complex Interfaces.

PMID- 26292252
TI  - Unraveling the Complex Nature of the Hydrated Electron.
AB  - The structure of the hydrated electron, which is a key species in radiative
      processes in water, has remained elusive. The traditional cavity model has been
      questioned recently, but the newly suggested picture of an electron delocalized
      over a region of enhanced water density is controversial. Here, we present
      results from ab initio molecular dynamics simulations, where not only the excess
      electron but also the valence electrons of the surrounding water molecules are
      described quantum mechanically. Unlike in previous one-electron pseudopotential
      calculations, many-electron interactions are explicitly accounted for. The
      present approach allows for partitioning of the electron solvated in liquid water
      into contributions from an inner cavity, neighboring water molecules, and a
      diffuse tail. We demonstrate that all three of these contributions are sizable
      and, consequently, important, which underlines the complex nature of the hydrated
      electron and warns against oversimplified interpretations based on
      pseudopotential models. 

PMID- 26292253
TI  - Experimental and Theoretical Determination of the Optical Gap of the
      Au144(SC2H4Ph)60 Cluster and the (Au/Ag)144(SC2H4Ph)60 Nanoalloys.
AB  - Au144PET60 and Au144-xAgxPET60 (PET = SC2H4Ph, phenylethylthiolate, and 30 <= x
      <= 53) clusters were studied by optical spectroscopy and linear response time
      dependent density functional theory. Spectra of thin dry films were measured in
      order to reveal the onset for electronic absorption. The optical gap of the
      Au144PET60 cluster was determined at 0.19 +/- 0.01 eV, which agrees well with the
      computed energy for the first optical transition at 0.32 eV for a model cluster
      Au144(SH)60 when the line width of individual transitions is taken into account.
      The optical gaps for the Au144-xAgxPET60 alloy clusters were observed in a range
      of 0.12-0.26 eV, in good agreement with the calculations giving 0.16-0.36 eV for
      the lowest-energy optical transitions for corresponding Au144-xAgx(SH)60 models.
      This indicates that the gap is only moderately affected by doping Au with Ag.
      This work constitutes the first accurate determination of the fundamental
      spectroscopic gap of these compounds. 

PMID- 26292256
TI  - Two Loops Undergoing Concerted Dynamics Regulate the Activity of the ASH1L
      Histone Methyltransferase.
AB  - ASH1L (absent, small, or homeotic-like 1) is a histone methyltransferase (HMTase)
      involved in gene activation that is overexpressed in multiple forms of cancer.
      Previous studies of ASH1L's catalytic SET domain identified an autoinhibitory
      loop that blocks access of histone substrate to the enzyme active site. Here, we
      used both nuclear magnetic resonance and X-ray crystallography to identify
      conformational dynamics in the ASH1L autoinhibitory loop. Using site-directed
      mutagenesis, we found that point mutations in the autoinhibitory loop that
      perturb the structure of the SET domain result in decreased enzyme activity,
      indicating that the autoinhibitory loop is not a simple gate to the active site
      but is rather a key feature critical to ASH1L function. We also identified a
      second loop in the SET-I subdomain of ASH1L that experiences conformational
      dynamics, and we trapped two different conformations of this loop using
      crystallographic studies. Mutation of the SET-I loop led to a large decrease in
      ASH1L enzymatic activity in addition to a significant conformational change in
      the SET-I loop, demonstrating the importance of the structure and dynamics of the
      SET-I loop to ASH1L function. Furthermore, we found that three C-terminal
      chromatin-interacting domains greatly enhance ASH1L enzymatic activity and that
      ASH1L requires native nucleosome substrate for robust activity. Our study
      illuminates the role of concerted conformational dynamics in ASH1L function and
      identifies structural features important for ASH1L enzymatic activity. 

PMID- 26292258
TI  - Molecular detection and genotypic characterization of Toxoplasma gondii in wild
      waterfowls in Jilin Province, Northeastern China.
AB  - Toxoplasma gondii can infect almost warm-blooded animals, including humans.
      Limited information about T. gondii infection in wild waterfowls is available in
      China. The present study was conducted to determine prevalence and genotype T.
      gondii infection in 11 wild waterfowl species in Jilin Province, northeastern
      China. A total of 249 wild waterfowls were sampled between April and July 2013
      from Jilin Province, and the tissue samples were collected for the detection of
      T. gondii by a semi-nested PCR targeting the B1 gene. The positive samples were
      genotyped at 11 genetic markers (SAG1, 5'- and 3'-SAG2, alternative SAG2, SAG3,
      BTUB, GRA6, L358, PK1, c22-8, c29-2, and Apico) using multilocus polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) technology. The
      overall prevalence of T. gondii in the wild waterfowls was 7.2% (18/249, 95%
      confidence interval [CI] 4.0-10.4), with the highest prevalence (22.0%, 95% CI
      10.5-33.5) in Anas formosa, followed by Anas platyrhynchos (20.0%, 95% CI 6.0
      44.0), Falcated teal (12.5%, 95% CI 0.0-35.4), and Fulica atra (4.0%, 95% CI 0.0
      11.7). Of 18 positive samples, only 2 samples (TgWfjl1 and TgWfjl2) were
      genotyped completely, and one genotype, namely ToxoDB #9, was revealed. The
      result of this survey has implications for better understanding of the genetic
      diversity of T. gondii in China. This is the first report of prevalence and
      genotypic characterization of T. gondii in wild waterfowls in northeastern China.

PMID- 26292260
TI  - A comparative study of the effects of vein-joints on the mechanical behaviour of
      insect wings: I. Single joints.
AB  - The flight performance of insects is strongly affected by the deformation of the
      wing during a stroke cycle. Many insects therefore use both active and passive
      mechanisms to control the deformation of their wings in flight. Several studies
      have focused on the wing kinematics, and plenty is known about the mechanism of
      their passive deformability. However, given the small size of the vein-joints,
      accurate direct mechanical experiments are almost impossible to perform. We
      therefore developed numerical models to perform a comparative and comprehensive
      investigation of the mechanical behaviour of the vein-joints under external
      loading conditions. The results illustrate the effect of the geometry and the
      presence of the rubberlike protein resilin on the flexibility of the joints. Our
      simulations further show the contribution of the spikes to the anisotropic
      flexural stiffness in the dorsal and ventral directions. In addition, our results
      show that the cross veins, only in one joint type, help to transfer the stress to
      the thicker longitudinal veins. The deformation pattern and the stress
      distribution in each vein-joint are discussed in detail. This study provides a
      strong background for further realistic modelling of the dragonfly wing
      deformation. 

PMID- 26292259
TI  - Loss of NDRG2 promotes epithelial-mesenchymal transition of gallbladder carcinoma
      cells through MMP-19-mediated Slug expression.
AB  - BACKGROUND & AIMS: Gallbladder carcinoma (GBC) is the most common malignancy of
      the biliary tract and one of the most lethal forms of human cancer. However,
      there is limited information about the molecular pathogenesis of GBC. Here, we
      examined the functional role of the tumor suppressor N-myc downstream-regulated
      gene 2 (NDRG2) and the underlying molecular mechanisms of disease progression in
      GBC. METHODS: Clinical correlations between NDRG2 expression and
      clinicopathological factors were determined by immunohistochemical analysis of
      tumor tissues from 86 GBC patients. Biological functions of NDRG2 and NDRG2
      mediated signaling pathways were determined in GBC cell lines with NDRG2
      knockdown or overexpression. RESULTS: Loss of NDRG2 expression was an independent
      predictor of decreased survival and was significantly associated with a more
      advanced T stage, higher cellular grade, and lymphatic invasion in patients with
      GBC. GBC cells with loss of NDRG2 expression showed significantly enhanced
      proliferation, migration, and invasiveness in vitro, and tumor growth and
      metastasis in vivo. Loss of NDRG2 induced the expression of matrix
      metalloproteinase-19 (MMP-19), which regulated the expression of Slug at the
      transcriptional level. In addition, MMP-19-induced Slug, increased the expression
      of a receptor tyrosine kinase, Axl, which maintained Slug expression through a
      positive feedback loop, and stabilized epithelial-mesenchymal transition of GBC
      cells. CONCLUSIONS: The results of our study help to explain why the loss of
      NDRG2 expression is closely correlated with malignancy of GBC. These results
      strongly suggest that NDRG2 could be a favorable prognostic indicator and
      promising target for therapeutic agents against GBC.

PMID- 26292261
TI  - Synaptopathy--From Biology to Therapy.

PMID- 26292257
TI  - Discovery of Novel Plasmodium falciparum Pre-Erythrocytic Antigens for Vaccine
      Development.
AB  - BACKGROUND: Nearly 100% protection against malaria infection can be achieved in
      humans by immunization with P. falciparum radiation-attenuated sporozoites (RAS).
      Although it is thought that protection is mediated by T cell and antibody
      responses, only a few of the many pre-erythrocytic (sporozoite and liver stage)
      antigens that are targeted by these responses have been identified. METHODOLOGY:
      Twenty seven P. falciparum pre-erythrocytic antigens were selected using
      bioinformatics analysis and expression databases and were expressed in a wheat
      germ cell-free protein expression system. Recombinant proteins were recognized by
      plasma from RAS-immunized subjects, and 21 induced detectable antibody responses
      in mice and rabbit and sera from these immunized animals were used to
      characterize these antigens. All 21 proteins localized to the sporozoite: five
      localized to the surface, seven localized to the micronemes, cytoplasm,
      endoplasmic reticulum or nucleus, two localized to the surface and cytoplasm, and
      seven remain undetermined. PBMC from RAS-immunized volunteers elicited positive
      ex vivo or cultured ELISpot responses against peptides from 20 of the 21
      antigens. CONCLUSIONS: These T cell and antibody responses support our approach
      of using reagents from RAS-immunized subjects to screen potential vaccine
      antigens, and have led to the identification of a panel of novel P. falciparum
      antigens. These results provide evidence to further evaluate these antigens as
      vaccine candidates. TRIAL REGISTRATION: ClinicalTrials.gov NCT00870987
      ClinicalTrials.gov NCT00392015.

PMID- 26292262
TI  - Measuring Patients' Experience of Rehabilitation Services Across the Care
      Continuum. Part II: Key Dimensions.
AB  - OBJECTIVES: To identify key dimensions of patients' experience across the
      rehabilitative care system and to recommend a framework to develop survey items
      that measure the rehabilitative care experience. DATA SOURCES: Data were sourced
      from a literature review that searched MEDLINE (PubMed), CINAHL (Ebsco), and
      PsycINFO (APA PsycNET) databases from 2004 to 2014, the reference lists of the
      final accepted articles, and hand searches of relevant journals. STUDY SELECTION:
      Four reviewers performed the screening process on 2472 articles; 33 were included
      for analysis. Interrater reliability was confirmed through 2 rounds of title
      review and 1 round of abstract review, with an average kappa score of .69. DATA
      EXTRACTION: The final sample of 33 accepted articles was imported into a
      qualitative data analysis software application. Multiple levels of coding and a
      constant comparative methodology generated 6 themes. There were 502 discreet
      survey questions measuring patient experience that were categorized using the
      following dimensions: rehabilitative care ecosystem, client and informal
      caregiver engagement, patient and health care provider relation, pain and
      functional status, group and individual identity, and open ended. DATA SYNTHESIS:
      The most common survey questions examine the care delivery ecosystem (37%), the
      engagement of clients and their informal caregivers (24.9%), and the quality of
      relations between providers and patients (21.7%). Examination of patient's
      functional status and management of pain yielded (15.3%) of the instruments'
      questions. CONCLUSIONS: Currently available instruments and questions that
      measure patients' experience in rehabilitative care are unable to assess the
      performance of rehabilitative delivery systems that aspire to integrate care
      across the continuum. However, question panels derived from our 6 key themes may
      measure the key concepts that define rehabilitative care and facilitate
      measurement of patient experience at the system level.

PMID- 26292263
TI  - Gross Motor Function Measure Evolution Ratio: Use as a Control for Natural
      Progression in Cerebral Palsy.
AB  - OBJECTIVE: To develop a new way to interpret Gross Motor Function Measure (GMFM
      66) score improvement in studies conducted without control groups in children
      with cerebral palsy (CP). DESIGN: The curves, which describe the pattern of motor
      development according to the children's Gross Motor Function Classification
      System level, were used as historical control to define the GMFM-66 expected
      natural evolution in children with CP. These curves have been modeled and
      generalized to fit the curve to particular children characteristics. SETTING:
      Research center. PARTICIPANTS: Not applicable. INTERVENTIONS: Not applicable.
      MEAN OUTCOME MEASURES: Not applicable. RESULTS: Assuming that the GMFM-66 score
      evolution followed the shape of the Rosenbaum curves, by taking into account the
      age and GMFM-66 score of children, the expected natural evolution of the GMFM-66
      score was predicted for any group of children with CP who were <8 years old.
      Because the expected natural evolution could be predicted for a specific group of
      children with CP, the efficacy of a treatment could be determined by comparing
      the GMFM-66 score evolution measured before and after treatment with the expected
      natural evolution for the same period. A new index, the Gross Motor Function
      Measure Evolution Ratio, was defined as follows: Gross Motor Function Measure
      Evolution Ratio=measured GMFM-66 score change/expected natural evolution.
      CONCLUSIONS: For practical or ethical reasons, it is almost impossible to use
      control groups in studies evaluating effectiveness of many therapeutic
      modalities. The Gross Motor Function Measure Evolution Ratio gives the
      opportunity to take into account the expected natural evolution of the gross
      motor function of children with CP, which is essential to accurately interpret
      the therapy effect on the GMFM-66.

PMID- 26292264
TI  - Kinetically stable metal ligand charge transfer complexes as crosslinks in
      nanogels/hydrogels: Physical properties and cytotoxicity.
AB  - A terpyridine end-functionalized 8-arm poly(ethylene glycol) was prepared using
      the reaction of a 4'-aminopentanoxy substituted terpyridine with a p-nitrophenyl
      chloroformate activated PEG-(OH)8. Supramolecular complexation of the polymer
      terpyridine moieties by Fe(2+) ions was investigated using NMR, UV-Vis and
      dynamic light scattering experiments. At low concentrations addition of Fe(2+)
      ions to an aqueous solution of the polymer conjugate afforded nanogels with a
      single size distribution around 250 nm. At concentrations above 3 wt%, and at a
      1:2 metal to ligand molar ratio, hydrogels were formed with increasing mechanical
      properties at increasing polymer concentrations. Using bovine chondrocytes, the
      biocompatibility and potential cytotoxicity of the polymer conjugate, nanogels
      and hydrogels were studied. The polymer conjugate with free ligands was toxic to
      the cells likely due to depletion of essential metal ions. When the terpyridine
      groups were complexed with Fe(2+) ions, both nanogel suspensions and hydrogels
      showed no cytotoxicity in direct contact with chondrocytes. Indirect contact of
      gels with chondrocytes using transwells revealed the absence of toxic components
      by leaching. A Live-Dead assay on chondrocytes encapsulated in the hydrogels
      indicated that the hydrogels are cytocompatible, revealing the potential use of
      these materials for biomedical and pharmaceutical applications. STATEMENT OF
      SIGNIFICANCE: The binding between transition metal ions and ligands with multiple
      binding sites can be almost as strong as covalent bonds. This metal-ligand charge
      transfer (MLCT) complexation was used to crosslink water soluble polymers into
      hydrogels. This approach to novel materials may find applications in the
      biomedical and pharmaceutical fields. Transition metal ions are essential trace
      elements present in tissue but up to now no cytotoxicity data of free ligands are
      available. Data presented show that free ligands are toxic to cells likely by
      depletion of trace metal ions, whereas kinetically stable complexes are not
      cytotoxic even when embedded in hydrogels. These results provide fundamental
      issues to be considered in the design of hydrogels crosslinked through metal
      ligand complexation.

PMID- 26292265
TI  - Charge-conversional zwitterionic copolymer as pH-sensitive shielding system for
      effective tumor treatment.
AB  - A novel pH-responsive gene delivery system for tumor acidity-targeted pDNA
      delivery is prepared by introducing a rapid charge-conversional zwitterionic
      copolymer to the positive surface of PEI/pDNA complexes through electrostatic
      interaction. The shielding system (OEAL) consists of oligoethylenimine (OEI),
      poly(l-aspartate) (PBLA), and poly(l-lysine) (PLL). The charge-conversional
      behavior of the OEAL/PEI/DNA ternary complex is evaluated by zeta potential
      assay. The surface charges of the complexes can change from negative to positive
      in the pH range of 7.4-6.8. Under a simulative in vivo environment, OEAL/PEI/DNA
      exhibits promotion of cellular uptake by tumor cells and enhanced gene
      transfection efficiency because of its good charge-conversional properties.
      Antitumor experiments further show that the pH-responsive charge-conversional
      system can mediate a therapeutic gene that can induce tumor apoptosis (pKH3-rev
      casp-3) to achieve effective tumor inhibition. Accordingly, OEAL can be regarded
      as a promising tumor microenvironment-sensitive gene delivery shielding system
      for antitumor therapy. STATEMENT OF SIGNIFICANCE: This manuscript focused on the
      novel pH-responsive gene delivery system for tumor acidity-targeted pDNA
      delivery. The novel system is prepared by introducing a rapid charge-conversional
      zwitterionic copolymer, consisting of oligoethylenimine, poly(l-aspartate) and
      poly(l-lysine), to the positive surface of PEI/pDNA complexes. The surface
      charges of the complexes can change from negative to positive from pH 7.4 to 6.8.
      OEAL/PEI/DNA shows promoting cellular uptake by tumor cells and enhanced gene
      transfection efficiency. The antitumor experiments further show that the pH
      responsive charge conversional system can mediate pKH3-rev-casp-3 to achieve
      effective tumor inhibition. Accordingly, OEAL can be regarded as a promising
      tumor microenvironment sensitive gene delivery shielding system for antitumor
      therapy.

PMID- 26292266
TI  - A macrophage/fibroblast co-culture system using a cell migration chamber to study
      inflammatory effects of biomaterials.
AB  - Chronic inflammatory reactions hamper the use of biomaterials after implantation.
      Thus, the aim of the study was to develop a novel predictive in vitro
      macrophage/fibroblast co-culture model based on cell migration chambers that
      allows a timely and locally controlled interaction of both cell types to study
      the inflammatory responses of biomaterials in vitro. Here, self-assembled
      monolayers (SAMs) with different wettability and charge properties were used as
      model biomaterials on which co-cultures were established by use of fence chambers
      having internal and external compartments. This allowed establishing separated
      and mixed co-cultures of both cell types before and after removal of the chamber,
      respectively. The key advantages of this novel co-culture model included not only
      to establish a timely-resolved study of cytokine release, but also the ability to
      assess individual macrophage migration in both macrophage mono-cultures and co
      cultures. All inflammatory reactions in terms of macrophage adhesion, macrophage
      migration, foreign body giant cell (FBGC) formation, beta1 integrin expression
      and pro-inflammatory cytokine production were found strongly surface property
      dependent. The results show that the hydrophobic CH3 surface caused the strongest
      inflammatory reactions, whereas the hydrophilic/anionic COOH surface caused the
      least inflammatory response, indicating low and high biocompatibility of the
      surfaces, respectively. Most importantly, we found that both macrophage motility
      and directional movement were increased in the presence of fibroblasts in co
      cultures compared with macrophage mono-cultures. Overall, the novel co-culture
      system provides access to a range of parameters for studying inflammatory
      reactions and reveals how material surface properties affect the inflammatory
      responses. 

PMID- 26292268
TI  - Diet-induced obesity causes ghrelin resistance in reward processing tasks.
AB  - Diet-induced obesity (DIO) causes ghrelin resistance in hypothalamic Agouti
      related peptide (AgRP) neurons. However, ghrelin promotes feeding through actions
      at both the hypothalamus and mesolimbic dopamine reward pathways. Therefore, we
      hypothesized that DIO would also establish ghrelin resistance in the ventral
      tegmental area (VTA), a major site of dopaminergic cell bodies important in
      reward processing. We observed reduced sucrose and saccharin consumption in
      Ghrelin KO vs Ghrelin WT mice. Moreover, DIO reduced saccharin consumption
      relative to chow-fed controls. These data suggest that the deletion of ghrelin
      and high fat diet both cause anhedonia. To assess if these are causally related,
      we tested whether DIO caused ghrelin resistance in a classic model of drug
      reward, conditioned place preference (CPP). Chow or high fat diet (HFD) mice were
      conditioned with ghrelin (1mg/kg in 10ml/kg ip) in the presence or absence of
      food in the conditioning chamber. We observed a CPP to ghrelin in chow-fed mice
      but not in HFD-fed mice. HFD-fed mice still showed a CPP for cocaine (20mg/kg),
      indicating that they maintained the ability to develop conditioned behaviour. The
      absence of food availability during ghrelin conditioning sessions induced a
      conditioned place aversion, an effect that was still present in both chow and HFD
      mice. Bilateral intra-VTA ghrelin injection (0.33MUg/MUl in 0.5MUl) robustly
      increased feeding in both chow-fed and high fat diet (HFD)-fed mice; however,
      this was correlated with body weight only in the chow-fed mice. Our results
      suggest that DIO causes ghrelin resistance albeit not directly in the VTA. We
      suggest there is impaired ghrelin sensitivity in upstream pathways regulating
      reward pathways, highlighting a functional role for ghrelin linking appropriate
      metabolic sensing with reward processing. 

PMID- 26292269
TI  - Incidence, avoidance, and management of pulmonary artery injuries in percutaneous
      transluminal pulmonary angioplasty.

PMID- 26292270
TI  - Long-term evolution of pacemaker dependency after percutaneous aortic valve
      implantation with the corevalve prosthesis.

PMID- 26292267
TI  - The generation of knock-in mice expressing fluorescently tagged galanin receptors
      1 and 2.
AB  - The neuropeptide galanin has diverse roles in the central and peripheral nervous
      systems, by activating the G protein-coupled receptors Gal1, Gal2 and the less
      studied Gal3 (GalR1-3 gene products). There is a wealth of data on expression of
      Gal1-3 at the mRNA level, but not at the protein level due to the lack of
      specificity of currently available antibodies. Here we report the generation of
      knock-in mice expressing Gal1 or Gal2 receptor fluorescently tagged at the C
      terminus with, respectively, mCherry or hrGFP (humanized Renilla green
      fluorescent protein). In dorsal root ganglia (DRG) neurons expressing the highest
      levels of Gal1-mCherry, localization to the somatic cell membrane was detected by
      live-cell fluorescence and immunohistochemistry, and that fluorescence decreased
      upon addition of galanin. In spinal cord, abundant Gal1-mCherry immunoreactive
      processes were detected in the superficial layers of the dorsal horn, and highly
      expressing intrinsic neurons of the lamina III/IV border showed both somatic cell
      membrane localization and outward transport of receptor from the cell body,
      detected as puncta within cell processes. In brain, high levels of Gal1-mCherry
      immunofluorescence were detected within thalamus, hypothalamus and amygdala, with
      a high density of nerve endings in the external zone of the median eminence, and
      regions with lesser immunoreactivity included the dorsal raphe nucleus. Gal2
      hrGFP mRNA was detected in DRG, but live-cell fluorescence was at the limits of
      detection, drawing attention to both the much lower mRNA expression than to Gal1
      in mice and the previously unrecognized potential for translational control by
      upstream open reading frames (uORFs). 

PMID- 26292271
TI  - The impact of overweight/obesity duration on the association between physical
      activity and cardiovascular disease risk: an application of the "fat but fit"
      paradigm.

PMID- 26292272
TI  - Cardiomyocyte-specific deletion of ferroportin using MCK-Cre has no apparent
      effect on cardiac iron homeostasis.

PMID- 26292273
TI  - Role of medical therapy for prognosis in patients with peripheral artery disease.

PMID- 26292274
TI  - Pulmonary fixation sleeve embolism and its acute management.

PMID- 26292275
TI  - Validity of in-hospital mortality data among patients with acute myocardial
      infarction or stroke in National Health Insurance Research Database in Taiwan.
AB  - OBJECTIVE: The aim of this study was to determine the validity of in-hospital
      mortality records in the National Health Insurance Research Database (NHIRD) by
      cross-comparing with death records from the electronic medical records (EMR) of a
      medical center in southern Taiwan. METHODS: Data on patients admitted to the
      medical center for acute myocardial infarction (AMI) or stroke during the years
      2005 to 2010 were extracted from the two databases and cross-linkages with
      patients' characteristics (birth date, gender, admission date, and discharge
      date). While the death record was available in the catastrophic illness registry
      data files (CIRD), we also estimated the insurance status and death record in the
      CIRD subset using confirmed death cases. Additionally, agreement in comorbidities
      between records from the two databases was evaluated. RESULTS: A total of 6197
      cases were successfully linked, with a linkage rate of 96.56% of cases in the
      NHIRD when linked to those from the EMR. Among the linked population, 538 of 682
      patients retrieved as expired in the NHIRD were also so recorded in the EMR. This
      yielded a positive predictive value of 0.79 when the EMR was used as the gold
      standard. Patients having death records in both the CIRD subset and the EMR
      totaled 364, which yielded a percentage positive agreement rate of 76%. The
      consistency in comorbidity diagnoses between the two databases was more than 90%
      among matched cases. CONCLUSIONS: The accuracy of death records in the NHIRD was
      high, and appears to be a valid resource for population research in
      cardiovascular diseases.

PMID- 26292276
TI  - Activating transcription factor 3: A promising therapeutic target for remission
      myocardial ischemia reperfusion injury.

PMID- 26292277
TI  - Plasma pro-brain natriuretic peptide and electrocardiographic changes in
      combination improve risk prediction in persons without known heart disease.
AB  - BACKGROUND: Though the electrocardiogram(ECG) and plasma pro-brain-natriuretic
      peptide (pro-BNP) are widely used markers of subclinical cardiac injury and can
      be used to predict future cardiovascular disease(CVD), they could merely be
      markers of the same underlying pathology. We aimed to determine if ECG changes
      and pro-BNP are independent predictors of CVD and if the combination improves
      risk prediction in persons without known heart disease. METHODS: Pro-BNP and ECG
      were obtained on 5454 persons without known heart disease from the 4th round of
      the Copenhagen City Heart Study, a prospective cohort study. Median follow-up was
      10.4 years. High pro-BNP was defined as above 90th percentile of age and sex
      adjusted levels. The end-points were all-cause mortality and the combination of
      admission with ischemic heart disease, heart failure or CVD death. RESULTS: ECG
      changes were present in 907 persons and were associated with high levels of pro
      BNP. In a fully adjusted model both high pro-BNP and ECG changes remained
      significant predictors: all-cause mortality(high pro-BNP, no ECG changes: HR:
      1.43(1.12-1.82);P=0.005, low pro-BNP, ECG changes: HR: 1.22(1.05-1.42);P=0.009,
      and both high pro-BNP and ECG changes: HR: 1.99(1.54-2.59);P<0.001), CVD
      event(high pro-BNP, no ECG changes: HR: 1.94(1.45-2.58);P<0.001, low pro-BNP, ECG
      changes: HR: 1.55(1.29-1.87);P<0.001, and both high pro-BNP and ECG changes: HR:
      3.86(2.94-5.08);P<0.001). Adding the combination of pro-BNP and ECG changes to a
      fully adjusted model correctly reclassified 33.9%(26.5-41.3);P<0.001 on the
      continuous net reclassification scale for all-cause mortality and 49.7%(41.1
      58.4);P<0.001 for CVD event. CONCLUSION: Combining ECG changes and pro-BNP
      improves risk prediction in persons without known heart disease.

PMID- 26292278
TI  - A Magnetic Wormhole.
AB  - Wormholes are fascinating cosmological objects that can connect two distant
      regions of the universe. Because of their intriguing nature, constructing a
      wormhole in a lab seems a formidable task. A theoretical proposal by Greenleaf et
      al. presented a strategy to build a wormhole for electromagnetic waves. Based on
      metamaterials, it could allow electromagnetic wave propagation between two points
      in space through an invisible tunnel. However, an actual realization has not been
      possible until now. Here we construct and experimentally demonstrate a
      magnetostatic wormhole. Using magnetic metamaterials and metasurfaces, our
      wormhole transfers the magnetic field from one point in space to another through
      a path that is magnetically undetectable. We experimentally show that the
      magnetic field from a source at one end of the wormhole appears at the other end
      as an isolated magnetic monopolar field, creating the illusion of a magnetic
      field propagating through a tunnel outside the 3D space. Practical applications
      of the results can be envisaged, including medical techniques based on magnetism.

PMID- 26292279
TI  - The Wnt Frizzled Receptor MOM-5 Regulates the UNC-5 Netrin Receptor through Small
      GTPase-Dependent Signaling to Determine the Polarity of Migrating Cells.
AB  - Wnt and Netrin signaling regulate diverse essential functions. Using a genetic
      approach combined with temporal gene expression analysis, we found a regulatory
      link between the Wnt receptor MOM-5/Frizzled and the UNC-6/Netrin receptor UNC-5.
      These two receptors play key roles in guiding cell and axon migrations, including
      the migration of the C. elegans Distal Tip Cells (DTCs). DTCs migrate post
      embryonically in three sequential phases: in the first phase along the Antero
      Posterior (A/P) axis, in the second, along the Dorso-Ventral (D/V) axis, and in
      the third, along the A/P axis. Loss of MOM-5/Frizzled function causes third phase
      A/P polarity reversals of the migrating DTCs. We show that an over-expression of
      UNC-5 causes similar DTC A/P polarity reversals and that unc-5 deficits markedly
      suppress the A/P polarity reversals caused by mutations in mom-5/frizzled. This
      implicates MOM-5/Frizzled as a negative regulator of unc-5. We provide further
      evidence that small GTPases mediate MOM-5's regulation of unc-5 such that one
      outcome of impaired function of small GTPases like CED-10/Rac and MIG-2/RhoG is
      an increase in unc-5 function. The work presented here demonstrates the existence
      of cross talk between components of the Netrin and Wnt signaling pathways and
      provides further insights into the way guidance signaling mechanisms are
      integrated to orchestrate directed cell migration. 

PMID- 26292281
TI  - Correction: A Difference-In-Differences Study of the Effects of a New Abandoned
      Building Remediation Strategy on Safety.

PMID- 26292280
TI  - Validity of Diagnostic Codes for Acute Stroke in Administrative Databases: A
      Systematic Review.
AB  - OBJECTIVE: To conduct a systematic review of studies reporting on the validity of
      International Classification of Diseases (ICD) codes for identifying stroke in
      administrative data. METHODS: MEDLINE and EMBASE were searched (inception to
      February 2015) for studies: (a) Using administrative data to identify stroke; or
      (b) Evaluating the validity of stroke codes in administrative data; and (c)
      Reporting validation statistics (sensitivity, specificity, positive predictive
      value (PPV), negative predictive value (NPV), or Kappa scores) for stroke, or
      data sufficient for their calculation. Additional articles were located by hand
      search (up to February 2015) of original papers. Studies solely evaluating codes
      for transient ischaemic attack were excluded. Data were extracted by two
      independent reviewers; article quality was assessed using the Quality Assessment
      of Diagnostic Accuracy Studies tool. RESULTS: Seventy-seven studies published
      from 1976-2015 were included. The sensitivity of ICD-9 430-438/ICD-10 I60-I69 for
      any cerebrovascular disease was >= 82% in most [>= 50%] studies, and specificity
      and NPV were both >= 95%. The PPV of these codes for any cerebrovascular disease
      was >= 81% in most studies, while the PPV specifically for acute stroke was <=
      68%. In at least 50% of studies, PPVs were >= 93% for subarachnoid haemorrhage
      (ICD-9 430/ICD-10 I60), 89% for intracerebral haemorrhage (ICD-9 431/ICD-10 I61),
      and 82% for ischaemic stroke (ICD-9 434/ICD-10 I63 or ICD-9 434&436). For in
      hospital deaths, sensitivity was 55%. For cerebrovascular disease or acute stroke
      as a cause-of-death on death certificates, sensitivity was <= 71% in most studies
      while PPV was >= 87%. CONCLUSIONS: While most cases of prevalent cerebrovascular
      disease can be detected using 430-438/I60-I69 collectively, acute stroke must be
      defined using more specific codes. Most in-hospital deaths and death certificates
      with stroke as a cause-of-death correspond to true stroke deaths. Linking vital
      statistics and hospitalization data may improve the ascertainment of fatal
      stroke.

PMID- 26292282
TI  - Secular Trends of Gestational Diabetes Mellitus and Changes in Its Risk Factors.
AB  - OBJECTIVE: The aim of this study was to evaluate the secular trends of incidence
      of gestational diabetes mellitus (GDM) and insulin treatment for GDM in a Korean
      population and to determine the factors that contribute to the trends in the
      incidence of GDM. STUDY DESIGN: We used data collected by the Health Insurance
      Review & Assessment Service of Korea and analyzed data from women who had given
      birth from 2006 to 2010. We evaluated the trends in the incidence of GDM and GDM
      requiring insulin treatment and the changes in risk factors. RESULTS: There were
      1,824,913 births during the study period, which included 129,666 cases of GDM, an
      incidence of 7.11% over this period. The incidence of GDM increased from 3.86% in
      2007 to 11.83% in 2010, with a continuous increase after adjustment for age.
      However, the number of GDM cases that required insulin treatment decreased
      significantly from 13.87% in 2007 to 5.94% in 2010. The proportion of patients
      who were at an older age and multiparity, 2 GDM risk factors, increased during
      the study period. CONCLUSIONS: In Korea, the incidence of GDM, especially mild
      GDM, increased dramatically during the period from 2006 to 2010. Further efforts
      are needed to monitor this trend and to identify associated factors.

PMID- 26292283
TI  - Human Articular Cartilage Progenitor Cells Are Responsive to Mechanical
      Stimulation and Adenoviral-Mediated Overexpression of Bone-Morphogenetic Protein
      2.
AB  - Articular cartilage progenitor cells (ACPCs) represent a new and potentially
      powerful alternative cell source to commonly used cell sources for cartilage
      repair, such as chondrocytes and bone-marrow derived mesenchymal stem cells
      (MSCs). This is particularly due to the apparent resistance of ACPCs to
      hypertrophy. The current study opted to investigate whether human ACPCs (hACPCs)
      are responsive towards mechanical stimulation and/or adenoviral-mediated
      overexpression of bone morphogenetic protein 2 (BMP-2). hACPCs were cultured in
      fibrin-polyurethane composite scaffolds. Cells were cultured in a defined chondro
      permissive medium, lacking exogenous growth factors. Constructs were cultured,
      for 7 or 28 days, under free-swelling conditions or with the application of
      complex mechanical stimulation, using a custom built bioreactor that is able to
      generate joint-like movements. Outcome parameters were quantification of BMP-2
      and transforming growth factor beta 1 (TGF-beta1) concentration within the cell
      culture medium, biochemical and gene expression analyses, histology and
      immunohistochemistry. The application of mechanical stimulation alone resulted in
      the initiation of chondrogenesis, demonstrating the cells are mechanoresponsive.
      This was evidenced by increased GAG production, lack of expression of
      hypertrophic markers and a promising gene expression profile (significant up
      regulation of cartilaginous marker genes, specifically collagen type II,
      accompanied by no increase in the hypertrophic marker collagen type X or the
      osteogenic marker alkaline phosphatase). To further investigate the resistance of
      ACPCs to hypertrophy, overexpression of a factor associated with hypertrophic
      differentiation, BMP-2, was investigated. A novel, three-dimensional,
      transduction protocol was used to transduce cells with an adenovirus coding for
      BMP-2. Over-expression of BMP-2, independent of load, led to an increase in
      markers associated with hypertropy. Taken together ACPCs represent a potential
      alterative cell source for cartilage tissue engineering applications. 

PMID- 26292284
TI  - Protection against the Metabolic Syndrome by Guar Gum-Derived Short-Chain Fatty
      Acids Depends on Peroxisome Proliferator-Activated Receptor gamma and Glucagon
      Like Peptide-1.
AB  - The dietary fiber guar gum has beneficial effects on obesity, hyperglycemia and
      hypercholesterolemia in both humans and rodents. The major products of colonic
      fermentation of dietary fiber, the short-chain fatty acids (SCFAs), have been
      suggested to play an important role. Recently, we showed that SCFAs protect
      against the metabolic syndrome via a signaling cascade that involves peroxisome
      proliferator-activated receptor (PPAR) gamma repression and AMP-activated protein
      kinase (AMPK) activation. In this study we investigated the molecular mechanism
      via which the dietary fiber guar gum protects against the metabolic syndrome.
      C57Bl/6J mice were fed a high-fat diet supplemented with 0% or 10% of the fiber
      guar gum for 12 weeks and effects on lipid and glucose metabolism were studied.
      We demonstrate that, like SCFAs, also guar gum protects against high-fat diet
      induced metabolic abnormalities by PPARgamma repression, subsequently increasing
      mitochondrial uncoupling protein 2 expression and AMP/ATP ratio, leading to the
      activation of AMPK and culminating in enhanced oxidative metabolism in both liver
      and adipose tissue. Moreover, guar gum markedly increased peripheral glucose
      clearance, possibly mediated by the SCFA-induced colonic hormone glucagon-like
      peptide-1. Overall, this study provides novel molecular insights into the
      beneficial effects of guar gum on the metabolic syndrome and strengthens the
      potential role of guar gum as a dietary-fiber intervention. 

PMID- 26292285
TI  - Opposite Distortions in Interval Timing Perception for Visual and Auditory
      Stimuli with Temporal Modulations.
AB  - When an object is presented visually and moves or flickers, the perception of its
      duration tends to be overestimated. Such an overestimation is called time
      dilation. Perceived time can also be distorted when a stimulus is presented
      aurally as an auditory flutter, but the mechanisms and their relationship to
      visual processing remains unclear. In the present study, we measured interval
      timing perception while modulating the temporal characteristics of visual and
      auditory stimuli, and investigated whether the interval times of visually and
      aurally presented objects shared a common mechanism. In these experiments,
      participants compared the durations of flickering or fluttering stimuli to
      standard stimuli, which were presented continuously. Perceived durations for
      auditory flutters were underestimated, while perceived durations of visual
      flickers were overestimated. When auditory flutters and visual flickers were
      presented simultaneously, these distortion effects were cancelled out. When
      auditory flutters were presented with a constantly presented visual stimulus, the
      interval timing perception of the visual stimulus was affected by the auditory
      flutters. These results indicate that interval timing perception is governed by
      independent mechanisms for visual and auditory processing, and that there are
      some interactions between the two processing systems. 

PMID- 26292286
TI  - Candidate Resistant Genes of Sand Pear (Pyrus pyrifolia Nakai) to Alternaria
      alternata Revealed by Transcriptome Sequencing.
AB  - Pear black spot (PBS) disease, which is caused by Alternaria alternata (Aa), is
      one of the most serious diseases affecting sand pear (Pyrus pyrifolia Nakai)
      cultivation worldwide. To investigate the defense mechanisms of sand pear in
      response to Aa, the transcriptome of a sand pear germplasm with differential
      resistance to Aa was analyzed using Illumina paired-end sequencing. Four
      libraries derived from PBS-resistant and PBS-susceptible sand pear leaves were
      characterized through inoculation or mock-inoculation. In total, 20.5 Gbp of
      sequence data and 101,632,565 reads were generated, representing 44717 genes.
      Approximately 66% of the genes or sequenced reads could be aligned to the pear
      reference genome. A large number (5213) of differentially expressed genes related
      to PBS resistance were obtained; 34 microsatellites were detected in these genes,
      and 28 genes were found to be closely related to PBS resistance. Using a
      transcriptome analysis in response to PBS inoculation and comparison analysis to
      the PHI database, 4 genes (Pbr039001, Pbr001627, Pbr025080 and Pbr023112) were
      considered to be promising candidates for sand pear resistance to PBS. This study
      provides insight into changes in the transcriptome of sand pear in response to
      PBS infection, and the findings have improved our understanding of the resistance
      mechanism of sand pear to PBS and will facilitate future gene discovery and
      functional genome studies of sand pear. 

PMID- 26292287
TI  - Erratum.
AB  - The Journal publishes corrections when they are of significance to patient care,
      scientific data or record-keeping, or authorship, whether that error was made by
      an author, editor, or staff. Errata also appear in the online version and are
      attached to files downloaded from jbjs.org.In the article entitled "The American
      Academy of Orthopaedic Surgeons Evidence-Based Guideline on Management of
      Anterior Cruciate Ligament Injuries" (2015 Apr 15; 97[8]: 672-4), the last name
      of one of the authors was spelled incorrectly. Specifically, "Gregory D. Meyer,
      PhD" should have read "Gregory D. Myer, PhD."

PMID- 26292288
TI  - HIF-1alpha Induces Multidrug Resistance in Gastric Cancer Cells by Inducing MiR
      27a.
AB  - This study aimed to determine the correlation between HIF-1alpha and miR-27a
      expression and to evaluate the effect of inhibition of HIF-1alpha expression on
      miR-27a expression and drug resistance in gastric cancer (GC). In the present
      study, real time-PCR and Western blot were performed to detect the expression of
      HIF-1alpha in GC tissues and cell lines. Then, OCUM-2MD3/L-OHP cells were
      transfected with HIF-1alpha-siRNA, a miR-27a mimic or pcDNA-HIF-1alpha, and cell
      survival was determined via the MTT assay. The expression of HIF-1alpha, miR-27a,
      and MDR-related genes was measured via real time-PCR and Western blot. ChIP and
      dual luciferase activity assays were performed to assess the transcriptional
      regulation of HIF-1alpha and miR-27a. The results revealed that transfection with
      HIF-1alpha-siRNA markedly decreased the levels of miR-27a, resulting in
      dramatically enhanced inhibition of the proliferation rate of OCUM-2MD3/L-OHP
      cells. Compared to non-transfected cells, the survival rate was significantly
      reduced in the cells transfected with HIF-1alpha-siRNA after treatment with L
      OHP. The cell survival rate was significantly increased in OCUM-2MD3/L-OHP cells
      transfected with the miR-27a mimic, whereas HIF-1alpha overexpression did not
      result in any clear change in cell survival. The results of the dual luciferase
      activity assay demonstrated that HIF-1alpha enhances the transcriptional activity
      of the miR27a promoter in cells transfected with a reporter plasmid containing
      the upstream promoter region of miR27a together with pcDNA-HIF-1alpha. ChIP
      analysis suggested that HIF-1alpha directly binds to the promoter region of
      miR27a. Inhibition of HIF-1alpha or miR27a expression decreased MDR1/P-gp, LRP,
      and Bcl-2 expression in OCUM-2MD3/L-OHP cells. Thus, we found that HIF-1alpha is
      closely associated with MDR in GC and that HIF-1alpha may suppress MDR1/P-gp, LRP
      and Bcl-2 expression by inhibiting miR-27a expression. 

PMID- 26292289
TI  - Error analysis and assessment of unsteady forces acting on a flapping wing micro
      air vehicle: free flight versus wind-tunnel experimental methods.
AB  - An accurate knowledge of the unsteady aerodynamic forces acting on a bio
      inspired, flapping-wing micro air vehicle (FWMAV) is crucial in the design
      development and optimization cycle. Two different types of experimental
      approaches are often used: determination of forces from position data obtained
      from external optical tracking during free flight, or direct measurements of
      forces by attaching the FWMAV to a force transducer in a wind-tunnel. This study
      compares the quality of the forces obtained from both methods as applied to a
      17.4 gram FWMAV capable of controlled flight. A comprehensive analysis of various
      error sources is performed. The effects of different factors, e.g., measurement
      errors, error propagation, numerical differentiation, filtering frequency
      selection, and structural eigenmode interference, are assessed. For the forces
      obtained from free flight experiments it is shown that a data acquisition
      frequency below 200 Hz and an accuracy in the position measurements lower than +/
      0.2 mm may considerably hinder determination of the unsteady forces. In general,
      the force component parallel to the fuselage determined by the two methods
      compares well for identical flight conditions; however, a significant difference
      was observed for the forces along the stroke plane of the wings. This was found
      to originate from the restrictions applied by the clamp to the dynamic
      oscillations observed in free flight and from the structural resonance of the
      clamped FWMAV structure, which generates loads that cannot be distinguished from
      the external forces. Furthermore, the clamping position was found to have a
      pronounced influence on the eigenmodes of the structure, and this effect should
      be taken into account for accurate force measurements. 

PMID- 26292290
TI  - Carnosol Inhibits Pro-Inflammatory and Catabolic Mediators of Cartilage Breakdown
      in Human Osteoarthritic Chondrocytes and Mediates Cross-Talk between Subchondral
      Bone Osteoblasts and Chondrocytes.
AB  - AIM: The aim of this work was to evaluate the effects of carnosol, a rosemary
      polyphenol, on pro-inflammatory and catabolic mediators of cartilage breakdown in
      chondrocytes and via bone-cartilage crosstalk. MATERIALS AND METHODS:
      Osteoarthritic (OA) human chondrocytes were cultured in alginate beads for 4 days
      in presence or absence of carnosol (6 nM to 9 MUM). The production of aggrecan,
      matrix metalloproteinase (MMP)-3, tissue inhibitor of metalloproteinase (TIMP)-1,
      interleukin (IL)-6 and nitric oxide (NO) and the expression of type II collagen
      and ADAMTS-4 and -5 were analyzed. Human osteoblasts from sclerotic (SC) or non
      sclerotic (NSC) subchondral bone were cultured for 3 days in presence or absence
      of carnosol before co-culture with chondrocytes. Chondrocyte gene expression was
      analyzed after 4 days of co-culture. RESULTS: In chondrocytes, type II collagen
      expression was significantly enhanced in the presence of 3 MUM carnosol (p =
      0.008). MMP-3, IL-6, NO production and ADAMTS-4 expression were down-regulated in
      a concentration-dependent manner by carnosol (p<0.01). TIMP-1 production was
      slightly increased at 3 MUM (p = 0.02) and ADAMTS-5 expression was decreased from
      0.2 to 9 MUM carnosol (p<0.05). IL-6 and PGE2 production was reduced in the
      presence of carnosol in both SC and NSC osteoblasts while alkaline phosphatase
      activity was not changed. In co-culture experiments preincubation of NSC and SC
      osteoblasts wih carnosol resulted in similar effects to incubation with anti-IL-6
      antibody, namely a significant increase in aggrecan and decrease in MMP-3, ADAMTS
      4 and -5 gene expression by chondrocytes. CONCLUSIONS: Carnosol showed potent
      inhibition of pro-inflammatory and catabolic mediators of cartilage breakdown in
      chondrocytes. Inhibition of matrix degradation and enhancement of formation was
      observed in chondrocytes cocultured with subchondral osteoblasts preincubated
      with carnosol indicating a cross-talk between these two cellular compartments,
      potentially mediated via inhibition of IL-6 in osteoblasts as similar results
      were obtained with anti-IL-6 antibody.

PMID- 26292291
TI  - Association of Human Papillomavirus 31 DNA Load with Risk of Cervical
      Intraepithelial Neoplasia Grades 2 and 3.
AB  - The association between human papillomavirus 31 (HPV31) DNA loads and the risk of
      cervical intraepithelial neoplasia grades 2 and 3 (CIN2-3) was evaluated among
      women enrolled in the atypical squamous cells of undetermined significance
      (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) triage study (ALTS),
      who were monitored semiannually over 2 years and who had HPV31 infections
      detected at >=1 visit. HPV31 DNA loads in the first HPV31-positive samples and in
      a random set of the last positive samples from women with >=2 HPV31-positive
      visits were measured by a real-time PCR assay. CIN2-3 was histologically
      confirmed at the same time as the first detection of HPV31 for 88 (16.6%) of 530
      women. After adjustment for HPV31 lineages, coinfection with other oncogenic
      types, and the timing of the first positive detection, the odds ratio (OR) per 1
      log-unit increase in viral loads for the risk of a concurrent diagnosis of CIN2-3
      was 1.5 (95% confidence interval [CI], 1.2 to 1.9). Of 373 women without CIN2-3
      at the first positive visit who had >=1 later visit, 44 had subsequent diagnoses
      of CIN2-3. The initial viral loads were associated with CIN2-3 diagnosed within 6
      months after the first positive visit (adjusted OR, 1.5 [95% CI, 1.0 to 2.4]) but
      were unrelated to CIN2-3 diagnosed later. For a random set of 49 women who were
      tested for viral loads at the first and last positive visits, changes in viral
      loads were upward and downward among women with and without follow-up CIN2-3
      diagnoses, respectively, although the difference was not statistically
      significant. Results suggest that HPV31 DNA load levels at the first positive
      visit signal a short-term but not long-term risk of CIN2-3. 

PMID- 26292292
TI  - Development of a Pefloxacin Disk Diffusion Method for Detection of
      Fluoroquinolone-Resistant Salmonella enterica.
AB  - Fluoroquinolones (FQs) are among the drugs of choice for treatment of Salmonella
      infections. However, fluoroquinolone resistance is increasing in Salmonella due
      to chromosomal mutations in the quinolone resistance-determining regions (QRDRs)
      of the topoisomerase genes gyrA, gyrB, parC, and parE and/or plasmid-mediated
      quinolone resistance (PMQR) mechanisms including qnr variants, aac(6')-Ib-cr,
      qepA, and oqxAB. Some of these mutations cause only subtle increases in the MIC,
      i.e., MICs ranging from 0.12 to 0.25 mg/liter for ciprofloxacin (just above the
      wild-type MIC of <=0.06 mg/liter). These isolates are difficult to detect with
      standard ciprofloxacin disk diffusion, and plasmid-mediated resistance, such as
      qnr, is often not detected by the nalidixic acid screen test. We evaluated 16
      quinolone/fluoroquinolone disks for their ability to detect low-level-resistant
      Salmonella enterica isolates that are not serotype Typhi. A total of 153
      Salmonella isolates characterized for the presence (n = 104) or absence (n = 49)
      of gyrA and/or parC topoisomerase mutations, qnrA, qnrB, qnrD, qnrS, aac(6')-Ib
      cr, or qepA genes were investigated. All isolates were MIC tested by broth
      microdilution against ciprofloxacin, levofloxacin, and ofloxacin and by disk
      diffusion using EUCAST or CLSI methodology. MIC determination correctly
      categorized all isolates as either wild-type isolates (MIC of <=0.06 mg/liter and
      absence of resistance genes) or non-wild-type isolates (MIC of >0.06 mg/liter and
      presence of a resistance gene). Disk diffusion using these antibiotics and
      nalidixic acid failed to detect some low-level-resistant isolates, whereas the 5
      MUg pefloxacin disk correctly identified all resistant isolates. However,
      pefloxacin will not detect isolates having aac(6')-Ib-cr as the only resistance
      determinant. The pefloxacin disk assay was approved and implemented by EUCAST (in
      2014) and CLSI (in 2015). 

PMID- 26292293
TI  - Evaluation of Surrogate Disk Tests for Detection of Ciprofloxacin and
      Levofloxacin Resistance in Clinical Isolates of Salmonella enterica.
AB  - Detection of fluoroquinolone resistance in Salmonella enterica has become
      increasingly difficult due to evolving resistance mechanisms to this
      antimicrobial class in this organism. We evaluated two quinolone disks and five
      fluoroquinolone disks for their ability to act as a surrogate agent for the
      detection of fluoroquinolone resistance in a collection of 136 S. enterica
      isolates, including 111 with intermediate or resistant ciprofloxacin MICs
      mediated by a variety of resistance mechanisms. Ciprofloxacin, ofloxacin, and
      pefloxacin disks detected all isolates resistant to ciprofloxacin (0% very major
      error) and yielded false resistance (major error) in 8, 4, and 12% of susceptible
      isolates, respectively. Ciprofloxacin and pefloxacin provided clearer
      differentiation of susceptible and resistant isolates. 

PMID- 26292294
TI  - Identification of a Bovine Enteric Calicivirus, Kirklareli Virus, Distantly
      Related to Neboviruses, in Calves with Enteritis in Turkey.
AB  - A calicivirus was detected in neonatal calves with enteritis in Kirklareli,
      Thrace, Turkey. In the full-length genome, Kirklareli virus was related (48%
      nucleotide identity) to bovine enteric caliciviruses (Nebovirus genus). The virus
      was also detected in a herd in Ankara, Central Anatolia, but not in other Turkish
      prefectures. 

PMID- 26292295
TI  - Recurrent Methicillin-Resistant Staphylococcus aureus Cutaneous Abscesses and
      Selection of Reduced Chlorhexidine Susceptibility during Chlorhexidine Use.
AB  - We describe the selection of reduced chlorhexidine susceptibility during
      chlorhexidine use in a patient with two episodes of cutaneous USA300 methicillin
      resistant Staphylococcus aureus abscess. The second clinical isolate harbors a
      novel plasmid that encodes the QacA efflux pump. Greater use of chlorhexidine for
      disease prevention warrants surveillance for resistance. 

PMID- 26292296
TI  - M-Protein Analysis of Streptococcus pyogenes Isolates Associated with Acute
      Rheumatic Fever in New Zealand.
AB  - We applied an emm cluster typing system to group A Streptococcus strains in New
      Zealand, including those associated with acute rheumatic fever (ARF). We observed
      few so-called rheumatogenic emm types but found a high proportion of emm types
      previously associated with pyoderma, further suggesting a role for skin infection
      in ARF. 

PMID- 26292297
TI  - Clonal Diversification and Changes in Lipid Traits and Colony Morphology in
      Mycobacterium abscessus Clinical Isolates.
AB  - The smooth-to-rough colony morphology shift in Mycobacterium abscessus has been
      implicated in loss of glycopeptidolipid (GPL), increased pathogenicity, and
      clinical decline in cystic fibrosis (CF) patients. However, the evolutionary
      phenotypic and genetic changes remain obscure. Serial isolates from nine non-CF
      patients with persistent M. abscessus infection were characterized by colony
      morphology, lipid profile via thin-layer chromatography and matrix-assisted laser
      desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), sequencing
      of eight genes in the GPL locus, and expression level of fadD23, a key gene
      involved in the biosynthesis of complex lipids. All 50 isolates were typed as M.
      abscessus subspecies abscessus and were clonally related within each patient.
      Rough isolates, all lacking GPL, predominated at later disease stages, some
      showing variation within rough morphology. While most (77%) rough isolates
      harbored detrimental mutations in mps1 and mps2, 13% displayed previously
      unreported mutations in mmpL4a and mmpS4, the latter yielding a putative GPL
      precursor. Two isolates showed no deleterious mutations in any of the eight genes
      sequenced. Mixed populations harboring different GPL locus mutations were
      detected in 5 patients, demonstrating clonal diversification, which was likely
      overlooked by conventional acid-fast bacillus (AFB) culture methods. Our work
      highlights applications of MALDI-TOF MS beyond identification, focusing on
      mycobacterial lipids relevant in virulence and adaptation. Later isolates
      displayed accumulation of triacylglycerol and reduced expression of fadD23,
      sometimes preceding rough colony onset. Our results indicate that clonal
      diversification and a shift in lipid metabolism, including the loss of GPL, occur
      during chronic lung infection with M. abscessus. GPL loss alone may not account
      for all traits associated with rough morphology. 

PMID- 26292298
TI  - Evaluation of the RealTime HIV-1, Xpert HIV-1, and Aptima HIV-1 Quant Dx Assays
      in Comparison to the NucliSens EasyQ HIV-1 v2.0 Assay for Quantification of HIV-1
      Viral Load.
AB  - HIV-1 RNA monitoring, both before and during antiretroviral therapy, is an
      integral part of HIV management worldwide. Measurements of HIV-1 viral loads are
      expected to assess the copy numbers of all common HIV-1 subtypes accurately and
      to be equally sensitive at different viral loads. In this study, we compared for
      the first time the performance of the NucliSens v2.0, RealTime HIV-1, Aptima HIV
      1 Quant Dx, and Xpert HIV-1 viral load assays. Plasma samples (n = 404) were
      selected on the basis of their NucliSens v2.0 viral load results and HIV-1
      subtypes. Concordance, linear regression, and Bland-Altman plots were assessed,
      and mixed-model analysis was utilized to compare the analytical performance of
      the assays for different HIV-1 subtypes and for low and high HIV-1 copy numbers.
      Overall, high concordance (>83.89%), high correlation values (Pearson r values of
      >0.89), and good agreement were observed among all assays, although the Xpert and
      Aptima assays, which provided the most similar outputs (estimated mean viral
      loads of 2.67 log copies/ml [95% confidence interval [CI], 2.50 to 2.84 log
      copies/ml] and 2.68 log copies/ml [95% CI, 2.49 to 2.86 log copies/ml],
      respectively), correlated best with the RealTime assay (89.8% concordance, with
      Pearson r values of 0.97 to 0.98). These three assays exhibited greater precision
      than the NucliSens v2.0 assay. All assays were equally sensitive for subtype B
      and AG/G samples and for samples with viral loads of 1.60 to 3.00 log copies/ml.
      The NucliSens v2.0 assay underestimated A1 samples and those with viral loads of
      >3.00 log copies/ml. The RealTime assay tended to underquantify subtype C
      (compared to the Xpert and Aptima assays) and subtype A1 samples. The Xpert and
      Aptima assays were equally efficient for detection of all subtypes and viral
      loads, which renders these new assays most suitable for clinical HIV
      laboratories. 

PMID- 26292299
TI  - Blood Volume Required for Detection of Low Levels and Ultralow Levels of
      Organisms Responsible for Neonatal Bacteremia by Use of Bactec Peds Plus/F, Plus
      Aerobic/F Medium, and the BD Bactec FX System: an In Vitro Study.
AB  - We used an in vitro technique to investigate blood volumes required to detect
      bacteremia and fungemia with low concentrations of an organism. At 1 to 10
      CFU/ml, Escherichia coli, Staphylococcus epidermidis, Staphylococcus aureus,
      Listeria monocytogenes, Candida albicans, and Candida parapsilosis isolates were
      detected in volumes as low as 0.5 ml. Detection of Streptococcus agalactiae and
      detection of bacteremia at <1 CFU/ml were unreliable. 

PMID- 26292300
TI  - Molecular Assay for Detection of Ciprofloxacin Resistance in Neisseria
      gonorrhoeae Isolates from Cultures and Clinical Nucleic Acid Amplification Test
      Specimens.
AB  - We developed a real-time PCR assay to detect single nucleotide polymorphisms
      associated with ciprofloxacin resistance in specimens submitted for nucleic acid
      amplification testing (NAAT). All three single nucleotide polymorphism (SNP)
      targets produced high sensitivity and specificity values. The presence of >=2
      SNPs was sufficient to predict ciprofloxacin resistance in an organism. 

PMID- 26292301
TI  - Acute Hepatic Necrosis Caused by Salmonella enterica Serotype I 4,5,12:-:1,2 in a
      Dog.
AB  - Acute hepatic necrosis was diagnosed in a dog. Gram staining and fluorescence in
      situ hybridization identified Salmonella enterica in the liver, subsequently
      confirmed as S. enterica serotype I 4,5,12:-:1,2. This is the first report of
      acute hepatic necrosis with liver failure caused by Salmonella in a dog. 

PMID- 26292303
TI  - Detection of Neisseria gonorrhoeae Isolates from Tonsils and Posterior
      Oropharynx.
AB  - We examined the factors influencing gonorrhea detection at the pharynx. One
      hundred men infected with Neisseria gonorrhoeae were swabbed from the tonsils and
      posterior oropharynx. N. gonorrhoeae was reisolated from the tonsils and
      posterior oropharynx in 62% and 52%, respectively (P = 0.041). Culture positivity
      was greater with higher gonococcal DNA loads at the tonsils (P = 0.001) and
      oropharynx (P < 0.001). N. gonorrhoeae can be cultured from the tonsils and
      posterior oropharynx with greater isolation rates where gonococcal loads are
      higher. 

PMID- 26292302
TI  - Simultaneous Presence of Insertion Sequence Excision Enhancer and Insertion
      Sequence IS629 Correlates with Increased Diversity and Virulence in Shiga Toxin
      Producing Escherichia coli.
AB  - Although new serotypes of enterohemorrhagic Escherichia coli (EHEC) emerge
      constantly, the mechanisms by which these new pathogens arise and the reasons
      emerging serotypes tend to carry more virulence genes than other E. coli are not
      understood. An insertion sequence (IS) excision enhancer (IEE) was discovered in
      EHEC O157:H7 that promoted the excision of IS3 family members and generating
      various genomic deletions. One IS3 family member, IS629, actively transposes and
      proliferates in EHEC O157:H7 and enterotoxigenic E. coli (ETEC) O139 and O149.
      The simultaneous presence of the IEE and IS629 (and other IS3 family members) may
      be part of a system promoting not only adaptation and genome diversification in
      E. coli O157:H7 but also contributing to the development of pathogenicity among
      predominant serotypes. Prevalence comparisons of these elements in 461 strains,
      representing 72 different serotypes and 5 preassigned seropathotypes (SPT) A to
      E, showed that the presence of these two elements simultaneously was serotype
      specific and associated with highly pathogenic serotypes (O157 and top non-O157
      Shiga toxin-producing Escherichia coli [STEC]) implicated in outbreaks and
      sporadic cases of human illness (SPT A and B). Serotypes lacking one or both
      elements were less likely to have been isolated from clinical cases. Our
      comparisons of IEE sequences showed sequence variations that could be divided
      into at least three clusters. Interestingly, the IEE sequences from O157 and the
      top 10 non-O157 STEC serotypes fell into clusters I and II, while less commonly
      isolated serotypes O5 and O174 fell into cluster III. These results suggest that
      IS629 and IEE elements may be acting synergistically to promote genome plasticity
      and genetic diversity among STEC strains, enhancing their abilities to adapt to
      hostile environments and rapidly take up virulence factors.

PMID- 26292304
TI  - Utility of PCR, Culture, and Antigen Detection Methods for Diagnosis of
      Legionellosis.
AB  - The goal of this retrospective study was to evaluate the performance of different
      diagnostic tests for Legionnaires' disease in a clinical setting where Legionella
      pneumophila PCR had been introduced. Electronic medical records at the Cleveland
      Clinic were searched for Legionella urinary antigen (UAG), culture, and PCR tests
      ordered from March 2010 through December 2013. For cases where two or more test
      methods were performed and at least one was positive, the medical record was
      reviewed for relevant clinical and epidemiologic factors. Excluding repeat
      testing on a given patient, 19,912 tests were ordered (12,569 UAG, 3,747
      cultures, and 3,596 PCR) with 378 positive results. The positivity rate for each
      method was 0.4% for culture, 0.8% for PCR, and 2.7% for UAG. For 37 patients, at
      least two test methods were performed with at least one positive result: 10 (27%)
      cases were positive by all three methods, 16 (43%) were positive by two methods,
      and 11 (30%) were positive by one method only. For the 32 patients with medical
      records available, clinical presentation was consistent with proven or probable
      Legionella infection in 84% of the cases. For those cases, the sensitivities of
      culture, PCR, and UAG were 50%, 92%, and 96%, respectively. The specificities
      were 100% for culture and 99.9% for PCR and UAG. 

PMID- 26292305
TI  - Isolation on Chocolate Agar Culture of Legionella pneumophila Isolates from
      Subcutaneous Abscesses in an Immunocompromised Patient.
AB  - Cutaneous infections due to Legionella species have rarely been reported (L. J.
      Padrnos, J. E. Blair, S. Kusne, D. J. DiCaudo, and J. R. Mikhael, Transpl Infect
      Dis 16:307-314, 2014; P. W. Lowry, R. J. Blankenship, W. Gridley, N. J. Troup,
      and L. S. Tompkins, N Engl J Med 324:109-113, 1991; M. K. Waldor, B. Wilson, and
      M. Swartz, Clin Infect Dis 16:51-53, 1993). Here we report the identification of
      Legionella pneumophila isolates, from subcutaneous abscesses in an
      immunocompromised patient, that grew in an unusual medium for Legionella
      bacteria. 

PMID- 26292306
TI  - One-Step Multiplex PCR Assay for Differentiating Proposed New Species
      "Clostridium neonatale" from Closely Related Species.
AB  - "Clostridium neonatale" sp. nov., previously involved in an outbreak of neonatal
      necrotizing enterocolitis, was recently proposed as a new species of the
      Clostridium genus sensu stricto. We developed a one-step multiplex colony PCR for
      C. neonatale identification and investigated C. neonatale intestinal colonization
      frequency in healthy preterm neonates.

PMID- 26292307
TI  - Incidental Syphilis Diagnosed by Real-Time PCR Screening of Urine Samples.

PMID- 26292308
TI  - A Stewardship Approach To Optimize Antimicrobial Therapy through Use of a Rapid
      Microarray Assay on Blood Cultures Positive for Gram-Negative Bacteria.
AB  - A Gram-negative (GN) blood culture microarray assay with an antimicrobial
      stewardship program (ASP) intervention was evaluated in 126 patients with GN
      bacteremia. The median time to optimal therapy was shorter in the
      postintervention group than in the preintervention group (49.3 h versus 38.5 h,
      respectively; P = 0.0199). ASP can utilize microarray technology to decrease the
      time to optimal antimicrobial therapy. 

PMID- 26292309
TI  - Indirect Tris-EDTA Disk Testing Using Imipenem and Meropenem for Detection of OXA
      48 Carbapenemase Production.

PMID- 26292310
TI  - Mycobacterium tuberculosis pncA Polymorphisms That Do Not Confer Pyrazinamide
      Resistance at a Breakpoint Concentration of 100 Micrograms per Milliliter in
      MGIT.
AB  - Sequencing of the Mycobacterium tuberculosis pncA gene allows for pyrazinamide
      susceptibility testing. We summarize data on pncA polymorphisms that do not
      confer resistance at a susceptibility breakpoint of 100 MUg/ml pyrazinamide in
      MGIT within a cohort of isolates from South Africa and the U.S. Centers for
      Disease Control and Prevention. 

PMID- 26292311
TI  - Evaluation of the BD Max StaphSR Assay for Rapid Identification of Staphylococcus
      aureus and Methicillin-Resistant S. aureus in Positive Blood Culture Broths.
AB  - We evaluated the performance of the BD Max StaphSR assay for the direct detection
      of Staphylococcus aureus from blood culture medium. In a two-center trial, 155
      blood cultures from the BD Bactec FX system and 212 from the bioMerieux
      BacT/Alert system were tested; 170 bottles yielded S. aureus, and all were
      identified correctly by the BD Max StaphSR assay. The assay required
      approximately 2.5 h, thus allowing rapid identification of blood cultures flagged
      positive. 

PMID- 26292312
TI  - Nocardia thailandica Pulmonary Nocardiosis in a Post-Solid Organ Transplant
      Patient.
AB  - Nocardia thailandica is a rare pathogen related to Nocardia asteroides, Nocardia
      neocaledoniensis, and Nocardia caishijiensis that, since its original description
      in 2004, has only been reported to cause wound and ocular infections in humans.
      We report a case of pulmonary nocardiosis caused by Nocardia thailandica in a 66
      year-old solid organ transplant patient from Connecticut, which was identified at
      the molecular taxonomic level by secA1 analysis, 16S rRNA gene sequencing, and
      matrix-assisted laser desorption ionization-time of flight mass spectrometry
      (MALDI-TOF MS). To our knowledge, this is the first reported case of N.
      thailandica in the United States and the first report of pulmonary infection by
      this pathogen in the literature. 

PMID- 26292313
TI  - First Case of Fungemia Due to Pseudozyma aphidis in a Pediatric Patient with
      Osteosarcoma in Latin America.
AB  - We report the first case of blood infection due to Pseudozyma aphidis in Latin
      America. We contribute evidence showing this organism to be a potential human
      pathogen, and we provide new data about its identification, drug susceptibility,
      and treatment outcome. 

PMID- 26292314
TI  - Staphylococcus aureus Colonization and Strain Type at Various Body Sites among
      Patients with a Closed Abscess and Uninfected Controls at U.S. Emergency
      Departments.
AB  - Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is a
      prevalent cause of skin and soft tissue infections (SSTI), but the association
      between CA-MRSA colonization and infection remains uncertain. We studied the
      carriage frequency at several body sites and the diversity of S. aureus strains
      from patients with and without SSTI. Specimens from the nares, throat, rectum,
      and groin of case subjects with a closed skin abscess (i.e., without drainage)
      and matched control subjects without a skin infection (n = 147 each) presenting
      to 10 U.S. emergency departments were cultured using broth enrichment; wound
      specimens were cultured from abscess cases. Methicillin resistance testing and
      spa typing were performed for all S. aureus isolates. S. aureus was found in
      85/147 (57.8%) of abscesses; 49 isolates were MRSA, and 36 were methicillin
      susceptible S. aureus (MSSA). MRSA colonization was more common among cases
      (59/147; 40.1%) than among controls (27/147; 18.4%) overall (P < 0.001) and at
      each body site; no differences were observed for MSSA. S. aureus-infected
      subjects were usually (75/85) colonized with the infecting strain; among MRSA
      infected subjects, this was most common in the groin. The CC8 lineage accounted
      for most of both infecting and colonizing isolates, although more than 16
      distinct strains were identified. Nearly all MRSA infections were inferred to be
      USA300. There was more diversity among colonizing than infecting isolates and
      among those isolated from controls versus cases. CC8 S. aureus is a common
      colonizer of persons with and without skin infections. Detection of S. aureus
      colonization, and especially MRSA, may be enhanced by extranasal site culture. 

PMID- 26292316
TI  - New Diagnostic Insights for Macrorhabdus ornithogaster Infection.
AB  - The aim of this study was to propose the use of a new rapid and user-friendly
      diagnostic tool for the detection of Macrorhabdus ornithogaster infection in
      birds. The current report focuses on the diagnostic feasibility of different
      methods, with particular emphasis on the application of the mini-Flotac technique
      for the diagnosis of M. ornithogaster infection. The mini-Flotac method is
      particularly tailored for epidemiological monitoring and surveillance, where
      large numbers of fecal samples must be rapidly, yet reliably, examined. Gram
      staining, as the standard method, was used to validate the reliability of the
      mini-Flotac method. This tool has not yet been used in avian species or in the
      diagnosis of yeast infections. In our study, M. ornithogaster showed excellent
      performance in a flotation assay, which had not been demonstrated previously. Our
      results suggest that the mini-Flotac method is a valid, sensitive, and
      potentially low-cost alternative technique for use in the diagnosis of this yeast
      infection in birds. 

PMID- 26292315
TI  - Standardization of Quantitative PCR for Human T-Cell Leukemia Virus Type 1 in
      Japan: a Collaborative Study.
AB  - Quantitative PCR (qPCR) analysis of human T-cell leukemia virus type 1 (HTLV-1)
      was used to assess the amount of HTLV-1 provirus DNA integrated into the genomic
      DNA of host blood cells. Accumulating evidence indicates that a high proviral
      load is one of the risk factors for the development of adult T-cell
      leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis.
      However, interlaboratory variability in qPCR results makes it difficult to assess
      the differences in reported proviral loads between laboratories. To remedy this
      situation, we attempted to minimize discrepancies between laboratories through
      standardization of HTLV-1 qPCR in a collaborative study. TL-Om1 cells that harbor
      the HTLV-1 provirus were serially diluted with peripheral blood mononuclear cells
      to prepare a candidate standard. By statistically evaluating the proviral loads
      of the standard and those determined using in-house qPCR methods at each
      laboratory, we determined the relative ratios of the measured values in the
      laboratories to the theoretical values of the TL-Om1 standard. The relative
      ratios of the laboratories ranged from 0.84 to 4.45. Next, we corrected the
      proviral loads of the clinical samples from HTLV-1 carriers using the relative
      ratio. As expected, the overall differences between the laboratories were reduced
      by half, from 7.4-fold to 3.8-fold on average, after applying the correction.
      HTLV-1 qPCR can be standardized using TL-Om1 cells as a standard and by
      determining the relative ratio of the measured to the theoretical standard values
      in each laboratory. 

PMID- 26292317
TI  - Type I Interferons Triggered through the Toll-Like Receptor 3-TRIF Pathway
      Control Coxsackievirus A16 Infection in Young Mice.
AB  - Coxsackievirus A16 (CVA16) is one of the major etiological agents of hand, foot,
      and mouth disease (HFMD) in children. The host defense mechanisms against CVA16
      infection remain almost entirely unknown. Unlike previous observations with
      enterovirus 71 (EV71) infection, here we show that gamma interferon (IFN-gamma)
      or invariant NK T cell deficiency does not affect disease development or the
      survival of CVA16-infected mice. In contrast, type I interferon receptor
      deficiency resulted in the development of more severe disease in mice, and the
      mice had a lower survival rate than wild-type mice. Similarly, a deficiency of
      Toll-like receptor 3 (TLR3) and TRIF, but not other pattern recognition
      receptors, led to the decreased survival of CVA16-infected mice. TLR3-TRIF
      signaling was indispensable for the induction of type I interferons during CVA16
      infection in mice and protected young mice from disease caused by the infection.
      In particular, TRIF-mediated immunity was critical for preventing CVA16
      replication in the neuronal system before disease occurred. IFN-beta treatment
      was also found to compensate for TRIF deficiency in mice and decreased the
      disease severity in and mortality of CVA16-infected mice. Altogether, type I
      interferons induced by TLR3-TRIF signaling mediate protective immunity against
      CVA16 infection. These findings may shed light on therapeutic strategies to
      combat HFMD caused by CVA16 infection. IMPORTANCE: Hand, foot, and mouth disease
      (HFMD) is a major threat to public health in the Asia-Pacific region. Both CVA16
      and EV71 are major pathogens that are responsible for HFMD. The majority of
      research efforts have focused on the more virulent EV71, but little has been done
      with CVA16. Thus far, host immune responses to CVA16 infection have not yet been
      elucidated. The present study discovered an initial molecular mechanism
      underlying host protective immunity against CVA16 infection, providing the first
      explanation for why CVA16 and EV71 cause different clinical outcomes upon
      infection of humans. Therefore, different therapeutic strategies should be
      developed to treat HFMD cases caused by these two viruses.

PMID- 26292318
TI  - A Conserved Gammaherpesvirus Cyclin Specifically Bypasses Host p18(INK4c) To
      Promote Reactivation from Latency.
AB  - Gammaherpesviruses (GHVs) carry homologs of cellular genes, including those
      encoding a viral cyclin that promotes reactivation from latent infection. The
      viral cyclin has reduced sensitivity to host cyclin-dependent kinase inhibitors
      in vitro; however, the in vivo significance of this is unclear. Here, we tested
      the genetic requirement for the viral cyclin in mice that lack the host
      inhibitors p27(Kip1) and p18(INK4c), two cyclin-dependent kinase inhibitors known
      to be important in regulating B cell proliferation and differentiation. While the
      viral cyclin was essential for reactivation in wild-type mice, strikingly, it was
      dispensable for reactivation in mice lacking p27(Kip1) and p18(INK4c). Further
      analysis revealed that genetic ablation of only p18(INK4c) alleviated the
      requirement for the viral cyclin for reactivation from latency. p18(INK4c)
      regulated reactivation in a dose-dependent manner so that the viral cyclin was
      dispensable in p18(INK4c) heterozygous mice. Finally, treatment of wild-type
      cells with the cytokine BAFF, a known attenuator of p18(INK4c) function in B
      lymphocytes, was also able to bypass the requirement for the viral cyclin in
      reactivation. These data show that the gammaherpesvirus viral cyclin functions
      specifically to bypass the cyclin-dependent kinase inhibitor p18(INK4c),
      revealing an unanticipated specificity between a GHV cyclin and a single cyclin
      dependent kinase inhibitor. IMPORTANCE: The gammaherpesviruses (GHVs) cause
      lifelong infection and can cause chronic inflammatory diseases and cancer,
      especially in immunosuppressed individuals. Many GHVs encode a conserved viral
      cyclin that is required for infection and disease. While a common property of the
      viral cyclins is that they resist inhibition by normal cellular mechanisms, it
      remains unclear how important it is that the GHVs resist this inhibition. We used
      a mouse GHV that either contained or lacked a viral cyclin to test whether the
      viral cyclin lost importance when these inhibitory pathways were removed. These
      studies revealed that the viral cyclin was required for optimal function in
      normal mice but that it was no longer required following removal or reduced
      function of a single cellular inhibitor. These data define a very specific role
      for the viral cyclin in bypassing one cellular inhibitor and point to new methods
      to intervene with viral cyclins.

PMID- 26292319
TI  - Intracellular Signaling and Desmoglein 2 Shedding Triggered by Human Adenoviruses
      Ad3, Ad14, and Ad14P1.
AB  - We recently discovered that desmoglein 2 (DSG2) is a receptor for human
      adenovirus species B serotypes Ad3, Ad7, Ad11, and Ad14. Ad3 is considered to be
      a widely distributed human pathogen. Ad3 binding to DSG2 triggers the transient
      opening of epithelial junctions. Here, we further delineate the mechanism that
      leads to DSG2-mediated epithelial junction opening in cells exposed to Ad3 and
      recombinant Ad3 fiber proteins. We identified an Ad3 fiber knob-dependent pathway
      that involves the phosphorylation of mitogen-activated protein (MAP) kinases
      triggering the activation of the matrix-metalloproteinase ADAM17. ADAM17, in
      turn, cleaves the extracellular domain of DSG2 that links epithelial cells
      together. The shed DSG2 domain can be detected in cell culture supernatant and
      also in serum of mice with established human xenograft tumors. We then extended
      our studies to Ad14 and Ad14P1. Ad14 is an important research and clinical object
      because of the recent appearance of a new, more pathogenic strain (Ad14P1). In a
      human epithelial cancer xenograft model, Ad14P1 showed more efficient viral
      spread and oncolysis than Ad14. Here, we tested the hypothesis that a mutation in
      the Ad14P1 fiber knob could account for the differences between the two strains.
      While our X-ray crystallography studies suggested an altered three-dimensional
      (3D) structure of the Ad14P1 fiber knob in the F-G loop region, this did not
      significantly change the fiber knob affinity to DSG2 or the intracellular
      signaling and DSG2 shedding in epithelial cancer cells. IMPORTANCE: A number of
      widely distributed adenoviruses use the epithelial junction protein DSG2 as a
      receptor for infection and lateral spread. Interaction with DSG2 allows the virus
      not only to enter cells but also to open epithelial junctions which form a
      physical barrier to virus spread. Our study elucidates the mechanism beyond virus
      triggered junction opening with a focus on adenovirus serotype 3. Ad3 binds to
      DSG2 with its fiber knob domain and triggers intracellular signaling that
      culminates in the cleavage of the extracellular domain of DSG2, thereby
      disrupting DSG2 homodimers between epithelial cells. We confirmed this pathway
      with a second DSG2-interacting serotype, Ad14, and its recently emerged strain
      Ad14P1. These new insights in basic adenovirus biology can be employed to develop
      novel drugs to treat adenovirus infection as well as be used as tools for gene
      delivery into epithelial tissues or epithelial tumors.

PMID- 26292320
TI  - Breast Milk of HIV-Positive Mothers Has Potent and Species-Specific In Vivo HIV
      Inhibitory Activity.
AB  - Despite the nutritional and health benefits of breast milk, breast milk can serve
      as a vector for mother-to-child HIV transmission. Most HIV-infected infants
      acquire HIV through breastfeeding. Paradoxically, most infants breastfed by HIV
      positive women do not become infected. This is potentially attributed to anti-HIV
      factors in breast milk. Breast milk of HIV-negative women can inhibit HIV
      infection. However, the HIV-inhibitory activity of breast milk from HIV-positive
      mothers has not been evaluated. In addition, while significant differences in
      breast milk composition between transmitting and nontransmitting HIV-positive
      mothers have been correlated with transmission risk, the HIV-inhibitory activity
      of their breast milk has not been compared. This knowledge may significantly
      impact the design of prevention approaches in resource-limited settings that do
      not deny infants of HIV-positive women the health benefits of breast milk. Here,
      we utilized bone marrow/liver/thymus humanized mice to evaluate the in vivo HIV
      inhibitory activity of breast milk obtained from HIV-positive transmitting and
      nontransmitting mothers. We also assessed the species specificity and biochemical
      characteristics of milk's in vivo HIV-inhibitory activity and its ability to
      inhibit other modes of HIV infection. Our results demonstrate that breast milk of
      HIV-positive mothers has potent HIV-inhibitory activity and indicate that breast
      milk can prevent multiple routes of infection. Most importantly, this activity is
      unique to human milk. Our results also suggest multiple factors in breast milk
      may contribute to its HIV-inhibitory activity. Collectively, our results support
      current recommendations that HIV-positive mothers in resource-limited settings
      exclusively breastfeed in combination with antiretroviral therapy. IMPORTANCE:
      Approximately 240,000 children become infected with HIV annually, the majority
      via breastfeeding. Despite daily exposure to virus in breast milk, most infants
      breastfed by HIV-positive women do not acquire HIV. The low risk of breastfeeding
      associated HIV transmission is likely due to antiviral factors in breast milk. It
      is well documented that breast milk of HIV-negative women can inhibit HIV
      infection. Here, we demonstrate, for the first time, that breast milk of HIV
      positive mothers (nontransmitters and transmitters) inhibits HIV transmission. We
      also demonstrate that breast milk can prevent multiple routes of HIV acquisition
      and that this activity is unique to human milk. Collectively, our results support
      current guidelines which recommend that HIV-positive women in resource-limited
      settings exclusively breastfeed in combination with infant or maternal
      antiretroviral therapy.

PMID- 26292321
TI  - Dynamics of HIV-1 RNA Near the Plasma Membrane during Virus Assembly.
AB  - To increase our understanding of the events that lead to HIV-1 genome packaging,
      we examined the dynamics of viral RNA and Gag-RNA interactions near the plasma
      membrane by using total internal reflection fluorescence microscopy. We labeled
      HIV-1 RNA with a photoconvertible Eos protein via an RNA-binding protein that
      recognizes stem-loop sequences engineered into the viral genome. Near-UV light
      exposure causes an irreversible structural change in Eos and alters its emitted
      fluorescence from green to red. We studied the dynamics of HIV-1 RNA by
      photoconverting Eos near the plasma membrane, and we monitored the population of
      photoconverted red-Eos-labeled RNA signals over time. We found that in the
      absence of Gag, most of the HIV-1 RNAs stayed near the plasma membrane
      transiently, for a few minutes. The presence of Gag significantly increased the
      time that RNAs stayed near the plasma membrane: most of the RNAs were still
      detected after 30 min. We then quantified the proportion of HIV-1 RNAs near the
      plasma membrane that were packaged into assembling viral complexes. By tagging
      Gag with blue fluorescent protein, we observed that only a portion, ~13 to 34%,
      of the HIV-1 RNAs that reached the membrane were recruited into assembling
      particles in an hour, and the frequency of HIV-1 RNA packaging varied with the
      Gag expression level. Our studies reveal the HIV-1 RNA dynamics on the plasma
      membrane and the efficiency of RNA recruitment and provide insights into the
      events leading to the generation of infectious HIV-1 virions. IMPORTANCE: Nascent
      HIV-1 particles assemble on plasma membranes. During the assembly process, HIV-1
      RNA genomes must be encapsidated into viral complexes to generate infectious
      particles. To gain insights into the RNA packaging and virus assembly mechanisms,
      we labeled and monitored the HIV-1 RNA signals near the plasma membrane. Our
      results showed that most of the HIV-1 RNAs stayed near the plasma membrane for
      only a few minutes in the absence of Gag, whereas most HIV-1 RNAs stayed at the
      plasma membrane for 15 to 60 min in the presence of Gag. Our results also
      demonstrated that only a small proportion of the HIV-1 RNAs, approximately 1/10
      to 1/3 of the RNAs that reached the plasma membrane, was incorporated into viral
      protein complexes. These studies determined the dynamics of HIV-1 RNA on the
      plasma membrane and obtained temporal information on RNA-Gag interactions that
      lead to RNA encapsidation.

PMID- 26292322
TI  - Functional Comparison of Mx1 from Two Different Mouse Species Reveals the
      Involvement of Loop L4 in the Antiviral Activity against Influenza A Viruses.
AB  - The interferon-induced Mx1 gene is an important part of the mammalian defense
      against influenza viruses. Mus musculus Mx1 inhibits influenza A virus
      replication and transcription by suppressing the polymerase activity of viral
      ribonucleoproteins (vRNPs). Here, we compared the anti-influenza virus activity
      of Mx1 from Mus musculus A2G with that of its ortholog from Mus spretus. We found
      that the antiviral activity of M. spretus Mx1 was less potent than that of M.
      musculus Mx1. Comparison of the M. musculus Mx1 sequence with the M. spretus Mx1
      sequence revealed 25 amino acid differences, over half of which were present in
      the GTPase domain and 2 of which were present in loop L4. However, the in vitro
      GTPase activity of Mx1 from the two mouse species was similar. Replacement of one
      of the residues in loop L4 in M. spretus Mx1 by the corresponding residue of A2G
      Mx1 increased its antiviral activity. We also show that deletion of loop L4
      prevented the binding of Mx1 to influenza A virus nucleoprotein and, hence,
      abolished the antiviral activity of mouse Mx1. These results indicate that loop
      L4 of mouse Mx1 is a determinant of antiviral activity. Our findings suggest that
      Mx proteins from different mammals use a common mechanism to inhibit influenza A
      viruses. IMPORTANCE: Mx proteins are evolutionarily conserved in vertebrates and
      inhibit a wide range of viruses. Still, the exact details of their antiviral
      mechanisms remain largely unknown. Functional comparison of the Mx genes from two
      species that diverged relatively recently in evolution can provide novel insights
      into these mechanisms. We show that both Mus musculus A2G Mx1 and Mus spretus Mx1
      target the influenza virus nucleoprotein. We also found that loop L4 in mouse Mx1
      is crucial for its antiviral activity, as was recently reported for primate MxA.
      This indicates that human and mouse Mx proteins, which have diverged by 75
      million years of evolution, recognize and inhibit influenza A viruses by a common
      mechanism.

PMID- 26292323
TI  - Herpesvirus saimiri MicroRNAs Preferentially Target Host Cell Cycle Regulators.
AB  - In latently infected marmoset T cells, Herpesvirus saimiri (HVS) expresses six
      microRNAs (known as miR-HSURs [H. saimiri U-rich RNAs]). The viral miR-HSURs are
      processed from chimeric primary transcripts, each containing a noncoding U-rich
      RNA (HSUR) and a pre-miRNA hairpin. To uncover the functions of miR-HSURs, we
      identified mRNA targets in infected cells using high-throughput sequencing of RNA
      isolated by cross-linking immunoprecipitation (HITS-CLIP). HITS-CLIP revealed
      hundreds of robust Argonaute (Ago) binding sites mediated by miR-HSURs that map
      to the host genome but few in the HVS genome. Gene ontology analysis showed that
      several pathways regulating the cell cycle are enriched among cellular targets of
      miR-HSURs. Interestingly, miR-HSUR4-3p represses expression of the p300
      transcriptional coactivator by binding the open reading frame of its mRNA. miR
      HSUR5-3p directly regulates BiP, an endoplasmic reticulum (ER)-localized
      chaperone facilitating maturation of major histocompatibility complex class I
      (MHC-I) and the antiviral response. miR-HSUR5-3p also robustly downregulates
      WEE1, a key negative regulator of cell cycle progression, leading to reduced
      phosphorylation of its substrate, cyclin-dependent kinase (Cdk1). Consistently,
      inhibition of miR-HSUR5-3p in HVS-infected cells decreases their proliferation.
      Together, our results shed light on the roles of viral miRNAs in cellular
      transformation and viral latency. IMPORTANCE: Viruses express miRNAs during
      various stages of infection, suggesting that viral miRNAs play critical roles in
      the viral life cycle. Compared to protein-coding genes, the functions of viral
      miRNAs are not well understood. This is because it has been challenging to
      identify their mRNA targets. Here, we focused on the functions of the recently
      discovered HVS miRNAs, called miR-HSURs. HVS is an oncogenic gammaherpesvirus
      that causes acute T-cell lymphomas and leukemias in New World primates and
      transforms human T cells. A better understanding of HVS biology will help advance
      our knowledge of virus-induced oncogenesis. Because numerous cellular miRNAs play
      crucial roles in cancer, viral miRNAs from the highly oncogenic HVS might also be
      important for transformation. Here, we found that the miR-HSURs preferentially
      modulate expression of host cell cycle regulators, as well as antiviral response
      factors. Our work provides further insight into the functions of herpesviral
      miRNAs in virus-induced oncogenesis and latency.

PMID- 26292324
TI  - Adeno-Associated Virus Type 2 Rep68 Can Bind to Consensus Rep-Binding Sites on
      the Herpes Simplex Virus 1 Genome.
AB  - Adeno-associated virus type 2 is known to inhibit replication of herpes simplex
      virus 1 (HSV-1). This activity has been linked to the helicase- and DNA-binding
      domains of the Rep68/Rep78 proteins. Here, we show that Rep68 can bind to
      consensus Rep-binding sites on the HSV-1 genome and that the Rep helicase
      activity can inhibit replication of any DNA if binding is facilitated. Therefore,
      we hypothesize that inhibition of HSV-1 replication involves direct binding of
      Rep68/Rep78 to the HSV-1 genome. 

PMID- 26292325
TI  - Unique Determinants of Neuraminidase Inhibitor Resistance among N3, N7, and N9
      Avian Influenza Viruses.
AB  - Human infections with avian influenza viruses are a serious public health
      concern. The neuraminidase (NA) inhibitors (NAIs) are the frontline anti
      influenza drugs and are the major option for treatment of newly emerging
      influenza. Therefore, it is essential to identify the molecular markers of NAI
      resistance among specific NA subtypes of avian influenza viruses to help guide
      clinical management. NAI-resistant substitutions in NA subtypes other than N1 and
      N2 have been poorly studied. Here, we identified NA amino acid substitutions
      associated with NAI resistance among influenza viruses of N3, N7, and N9 subtypes
      which have been associated with zoonotic transmission. We applied random
      mutagenesis and generated recombinant influenza viruses carrying single or double
      NA substitution(s) with seven internal genes from A/Puerto Rico/8/1934 (H1N1)
      virus. In a fluorescence-based NA inhibition assay, we identified three
      categories of NA substitutions associated with reduced inhibition by NAIs
      (oseltamivir, zanamivir, and peramivir): (i) novel subtype-specific substitutions
      in or near the enzyme catalytic site (R152W, A246T, and D293N, N2 numbering),
      (ii) subtype-independent substitutions (E119G/V and/or D and R292K), and (iii)
      substitutions previously reported in other subtypes (Q136K, I222M, and E276D).
      Our data show that although some markers of resistance are present across NA
      subtypes, other subtype-specific markers can only be determined empirically.
      IMPORTANCE: The number of humans infected with avian influenza viruses is
      increasing, raising concerns of the emergence of avian influenza viruses
      resistant to neuraminidase (NA) inhibitors (NAIs). Since most studies have
      focused on NAI-resistance in human influenza viruses, we investigated the
      molecular changes in NA that could confer NAI resistance in avian viruses grown
      in immortalized monolayer cells, especially those of the N3, N7, and N9 subtypes,
      which have caused human infections. We identified not only numerous NAI-resistant
      substitutions previously reported in other NA subtypes but also several novel
      changes conferring reduced susceptibility to NAIs, which are subtype specific.
      The findings indicate that some resistance markers are common across NA subtypes,
      but other markers need to be determined empirically for each subtype. The study
      also implies that antiviral surveillance monitoring could play a critical role in
      the clinical management of influenza virus infection and an essential component
      of pandemic preparedness.

PMID- 26292326
TI  - Vaccine-Induced Simian Immunodeficiency Virus-Specific CD8+ T-Cell Responses
      Focused on a Single Nef Epitope Select for Escape Variants Shortly after
      Infection.
AB  - Certain major histocompatibility complex class I (MHC-I) alleles (e.g., HLA-B*27)
      are enriched among human immunodeficiency virus type 1 (HIV-1)-infected
      individuals who suppress viremia without treatment (termed "elite controllers"
      [ECs]). Likewise, Mamu-B*08 expression also predisposes rhesus macaques to
      control simian immunodeficiency virus (SIV) replication. Given the similarities
      between Mamu-B*08 and HLA-B*27, SIV-infected Mamu-B*08(+) animals provide a model
      to investigate HLA-B*27-mediated elite control. We have recently shown that
      vaccination with three immunodominant Mamu-B*08-restricted epitopes (Vif RL8, Vif
      RL9, and Nef RL10) increased the incidence of elite control in Mamu-B*08(+)
      macaques after challenge with the pathogenic SIVmac239 clone. Furthermore, a
      correlate analysis revealed that CD8(+) T cells targeting Nef RL10 was correlated
      with improved outcome. Interestingly, this epitope is conserved between SIV and
      HIV-1 and exhibits a delayed and atypical escape pattern. These features led us
      to postulate that a monotypic vaccine-induced Nef RL10-specific CD8(+) T-cell
      response would facilitate the development of elite control in Mamu-B*08(+)
      animals following repeated intrarectal challenges with SIVmac239. To test this,
      we vaccinated Mamu-B*08(+) animals with nef inserts in which Nef RL10 was either
      left intact (group 1) or disrupted by mutations (group 2). Although monkeys in
      both groups mounted Nef-specific cellular responses, only those in group 1
      developed Nef RL10-specific CD8(+) T cells. These vaccine-induced effector memory
      CD8(+) T cells did not prevent infection. Escape variants emerged rapidly in the
      group 1 vaccinees, and ultimately, the numbers of ECs were similar in groups 1
      and 2. High-frequency vaccine-induced CD8(+) T cells focused on a single
      conserved epitope and therefore did not prevent infection or increase the
      incidence of elite control in Mamu-B*08(+) macaques. IMPORTANCE: Since elite
      control of chronic-phase viremia is a classic example of an effective immune
      response against HIV/SIV, elucidating the basis of this phenomenon may provide
      useful insights into how to elicit such responses by vaccination. We have
      previously established that vaccine-induced CD8(+) T-cell responses against three
      immunodominant epitopes can increase the incidence of elite control in SIV
      infected Mamu-B*08(+) rhesus macaques-a model of HLA-B*27-mediated elite control.
      Here, we investigated whether a monotypic vaccine-induced CD8(+) T-cell response
      targeting the conserved "late-escaping" Nef RL10 epitope can increase the
      incidence of elite control in Mamu-B*08(+) monkeys. Surprisingly, vaccine-induced
      Nef RL10-specific CD8(+) T cells selected for variants within days after
      infection and, ultimately, did not facilitate the development of elite control.
      Elite control is, therefore, likely to involve CD8(+) T-cell responses against
      more than one epitope. Together, these results underscore the complexity and
      multidimensional nature of virologic control of lentivirus infection.

PMID- 26292327
TI  - Identification and Mechanism of Action of a Novel Small-Molecule Inhibitor of
      Arenavirus Multiplication.
AB  - Several arenaviruses cause hemorrhagic fever disease in humans and represent
      important public health problems in the regions where these viruses are endemic.
      In addition, evidence indicates that the worldwide-distributed prototypic
      arenavirus lymphocytic choriomeningitis virus (LCMV) is an important neglected
      human pathogen. There are no licensed arenavirus vaccines and current
      antiarenavirus therapy is limited to the use of ribavirin that is only partially
      effective. Therefore, there is an unmet need for novel antiarenaviral
      therapeutics. Here, we report the generation of a novel recombinant LCM virus and
      its use to develop a cell-based high-throughput screen to rapidly identify
      inhibitors of LCMV multiplication. We used this novel assay to screen a library
      of 30,400 small molecules and identified compound F3406 (chemical name: N-[3,5
      bis(fluoranyl)phenyl]-2-[5,7-bis(oxidanylidene)-6-propyl-2-pyrrolidin-1-yl
      [1,3]thiazolo[4,5-d]pyrimidin-4-yl]ethanamide), which exhibited strong anti-LCMV
      activity in the absence of cell toxicity. Mechanism-of-action studies revealed
      that F3406 inhibited LCMV cell entry by specifically interfering with the pH
      dependent fusion in the endosome compartment that is mediated by LCMV
      glycoprotein GP2 and required to release the virus ribonucleoprotein into the
      cell cytoplasm to initiate transcription and replication of the virus genome. We
      identified residue M437 within the transmembrane domain of GP2 as critical for
      virus susceptibility to F3406. IMPORTANCE: Hemorrhagic fever arenaviruses (HFA)
      are important human pathogens that cause high morbidity and mortality in areas
      where these viruses are endemic. In addition, evidence indicates that the
      worldwide-distributed prototypic arenavirus lymphocytic choriomeningitis virus
      (LCMV) is a neglected human pathogen of clinical significance. Concerns posed by
      arenavirus infections are aggravated by the lack of U.S. Food and Drug
      Administration-licensed arenavirus vaccines and current antiarenaviral therapy
      being limited to the off-label use of ribavirin that is only partially effective.
      Here we describe a novel recombinant LCMV and its use to develop a cell-based
      assay suitable for HTS to rapidly identify inhibitors arenavirus multiplication.
      The concepts and experimental strategies we describe in this work provide the
      bases for the rapid identification and characterization of novel anti-HFA
      therapeutics.

PMID- 26292328
TI  - Equine Herpesvirus Type 1 Enhances Viral Replication in CD172a+ Monocytic Cells
      upon Adhesion to Endothelial Cells.
AB  - Equine herpesvirus type 1 (EHV-1) is a main cause of respiratory disease,
      abortion, and encephalomyelopathy in horses. Monocytic cells (CD172a(+)) are the
      main carrier cells of EHV-1 during primary infection and are proposed to serve as
      a "Trojan horse" to facilitate the dissemination of EHV-1 to target organs.
      However, the mechanism by which EHV-1 is transferred from CD172a(+) cells to
      endothelial cells (EC) remains unclear. The aim of this study was to investigate
      EHV-1 transmission between these two cell types. We hypothesized that EHV-1
      employs specific strategies to promote the adhesion of infected CD172a(+) cells
      to EC to facilitate EHV-1 spread. Here, we demonstrated that EHV-1 infection of
      CD172a(+) cells resulted in a 3- to 5-fold increase in adhesion to EC. Antibody
      blocking experiments indicated that alpha4beta1, alphaLbeta2, and alphaVbeta3
      integrins mediated adhesion of infected CD172a(+) cells to EC. We showed that
      integrin-mediated phosphatidylinositol 3-kinase (PI3K) and ERK/MAPK signaling
      pathways were involved in EHV-1-induced CD172a(+) cell adhesion at early times of
      infection. EHV-1 replication was enhanced in adherent CD172a(+) cells, which
      correlates with the production of tumor necrosis factor alpha (TNF-alpha). In the
      presence of neutralizing antibodies, approximately 20% of infected CD172a(+)
      cells transferred cytoplasmic material to uninfected EC and 0.01% of infected
      CD172a(+) cells transmitted infectious virus to neighboring cells. Our results
      demonstrated that EHV-1 infection induces adhesion of CD172a(+) cells to EC,
      which enhances viral replication, but that transfer of viral material from
      CD172a(+) cells to EC is a very specific and rare event. These findings give new
      insights into the complex pathogenesis of EHV-1. IMPORTANCE: Equine herpesvirus
      type 1 (EHV-1) is a highly prevalent pathogen worldwide, causing frequent
      outbreaks of abortion and myeloencephalopathy, even in vaccinated horses. After
      primary replication in the respiratory tract, EHV-1 disseminates via cell
      associated viremia in peripheral blood mononuclear cells (PBMC) and subsequently
      infects the endothelial cells (EC) of the pregnant uterus or central nervous
      system, leading in some cases to abortion and/or neurological disorders.
      Recently, we demonstrated that CD172a(+) monocytic carrier cells serve as a
      "Trojan horse" to facilitate EHV-1 spread from blood to target organs. Here, we
      investigated the mechanism underlying the transmission of EHV-1 from CD172a(+)
      cells to EC. We demonstrated that EHV-1 infection induces cellular changes in
      CD172a(+) cells, promoting their adhesion to EC. We found that both cell-to-cell
      contacts and the secretion of soluble factors by EC activate EHV-1 replication in
      CD172a(+) cells. This facilitates transfer of cytoplasmic viral material to EC,
      resulting mainly in a nonproductive infection. Our findings give new insights
      into how EHV-1 may spread to EC of target organs in vaccinated horses.

PMID- 26292329
TI  - Transition toward Human Cytomegalovirus Susceptibility in Early Human Embryonic
      Stem Cell-Derived Neural Precursors.
AB  - Congenital human cytomegalovirus (HCMV) infection is associated with
      neurodevelopmental disabilities. To dissect the earliest events of infection in
      the developing human brain, we studied HCMV infection during controlled
      differentiation of human embryonic stem cells (hESC) into neural precursors. We
      traced a transition from viral restriction in hESC, mediated by a block in viral
      binding, toward HCMV susceptibility in early hESC-derived neural precursors. We
      further revealed the role of platelet-derived growth factor receptor alpha
      (PDGFRalpha) as a determinant of the developmentally acquired HCMV
      susceptibility. 

PMID- 26292330
TI  - Site-Specific Recombination by SSV2 Integrase: Substrate Requirement and Domain
      Functions.
AB  - SSV-type integrases, encoded by fuselloviruses which infect the hyperthermophilic
      archaea of the Sulfolobales, are archaeal members of the tyrosine recombinase
      family. These integrases catalyze viral integration into and excision from a
      specific site on the host genome. In the present study, we have established an in
      vitro integration/excision assay for SSV2 integrase (Int(SSV2)). Int(SSV2) alone
      was able to catalyze both integration and excision reactions in vitro. A 27-bp
      specific DNA sequence is minimally required for the activity of the enzyme, and
      its flanking sequences influence the efficiency of integration by the enzyme in a
      sequence-nonspecific manner. The enzyme forms a tetramer through interactions in
      the N-terminal part (residues 1 to 80), interacts nonspecifically with DNA and
      performs chemical catalysis in the C-terminal part (residues 165 to 328), and
      appears to recognize and bind the specific site of recombination in the middle
      portion (residues 81 to 164). It is worth noting that an N-terminally truncated
      mutant of Int(SSV2) (residues 81 to 328), which corresponded to the putative
      product of the 3'-end sequence of the Int(SSV2) gene of the integrated SSV2
      genome, was unable to form tetramers but possessed all the catalytic properties
      of full-length Int(SSV2) except for the slightly reduced recombination activity.
      Our results suggest that, unlike lambda integrase, SSV-type integrases alone are
      capable of catalyzing viral DNA recombination with the host genome in a simple
      and reversible fashion. IMPORTANCE: Archaea are host to a variety of viruses. A
      number of archaeal viruses are able to integrate their genome into the host
      genome. Many known archaeal viral integrases belong to a unique type, or the SSV
      type, of tyrosine recombinases. SSV-type integrases catalyze viral integration
      into and excision from a specific site on the host genome. However, the molecular
      details of the recombination process have yet to be fully understood because of
      the lack of an established in vitro recombination assay system. Here we report an
      in vitro assay for integration and excision by SSV2 integrase, a member of the
      SSV-type integrases. We show that SSV2 integrase alone is able to catalyze both
      integration and excision and reveal how different parts of the target DNA and the
      enzyme serve their roles in these processes. Therefore, our results provide
      mechanistic insights into a simple recombination process catalyzed by an archaeal
      integrase.

PMID- 26292331
TI  - Real-Time Classification of Bladder Events for Effective Diagnosis and Treatment
      of Urinary Incontinence.
AB  - Diagnosis of lower urinary tract dysfunction with urodynamics has historically
      relied on data acquired from multiple sensors using nonphysiologically fast
      cystometric filling. In addition, state-of-the-art neuromodulation approaches to
      restore bladder function could benefit from a bladder sensor for closed-loop
      control, but a practical sensor and automated data analysis are not available. We
      have developed an algorithm for real-time bladder event detection based on a
      single in situ sensor, making it attractive for both extended ambulatory bladder
      monitoring and closed-loop control of stimulation systems for diagnosis and
      treatment of bladder overactivity. Using bladder pressure data acquired from 14
      human subjects with neurogenic bladder, we developed context-aware thresholding,
      a novel, parameterized, user-tunable algorithmic framework capable of real-time
      classification of bladder events, such as detrusor contractions, from single
      sensor bladder pressure data. We compare six event detection algorithms with both
      single-sensor and two-sensor systems using a metric termed Conditional
      Stimulation Score, which ranks algorithms based on projected stimulation efficacy
      and efficiency. We demonstrate that adaptive methods are more robust against day
      to-day variations than static thresholding, improving sensitivity and specificity
      without parameter modifications. Relative to other methods, context-aware
      thresholding is fast, robust, highly accurate, noise-tolerant, and amenable to
      energy-efficient hardware implementation, which is important for mapping to an
      implant device. 

PMID- 26292332
TI  - Acoustic Source Analysis of Magnetoacoustic Tomography With Magnetic Induction
      for Conductivity Gradual-Varying Tissues.
AB  - GOAL: As a multiphysics imaging approach, magnetoacoustic tomography with
      magnetic induction (MAT-MI) works on the physical mechanism of magnetic
      excitation, acoustic vibration, and transmission. METHODS: Based on the
      theoretical analysis of the source vibration, numerical studies are conducted to
      simulate the pathological changes of tissues for a single-layer cylindrical
      conductivity gradual-varying model and estimate the strengths of sources inside
      the model. RESULTS: The results suggest that the inner source is generated by the
      product of the conductivity and the curl of the induced electric intensity inside
      conductivity homogeneous medium, while the boundary source is produced by the
      cross product of the gradient of conductivity and the induced electric intensity
      at conductivity boundary. CONCLUSION: For a biological tissue with low
      conductivity, the strength of boundary source is much higher than that of the
      inner source only when the size of conductivity transition zone is small. In this
      case, the tissue can be treated as a conductivity abrupt-varying model, ignoring
      the influence of inner source. Otherwise, the contributions of inner and boundary
      sources should be evaluated together quantitatively. SIGNIFICANCE: This study
      provide basis for further study of precise image reconstruction of MAT-MI for
      pathological tissues.

PMID- 26292333
TI  - Mind the Gap: A Semicontinuum Model for Discrete Electrical Propagation in
      Cardiac Tissue.
AB  - Electrical propagation in cardiac tissue is a discrete or discontinuous
      phenomenon that reflects the complexity of the anatomical structures and their
      organization in the heart, such as myocytes, gap junctions, microvessels, and
      extracellular matrix, just to name a few. Discrete models or microscopic and
      discontinuous models are, so far, the best options to accurately study how
      structural properties of cardiac tissue influence electrical propagation. These
      models are, however, inappropriate in the context of large scale simulations,
      which have been traditionally performed by the use of continuum and macroscopic
      models, such as the monodomain and the bidomain models. However, continuum models
      may fail to reproduce many important physiological and physiopathological aspects
      of cardiac electrophysiology, for instance, those related to slow conduction. In
      this study, we develop a new mathematical model that combines characteristics of
      both continuum and discrete models. The new model was evaluated in scenarios of
      low gap-junctional coupling, where slow conduction is observed, and was able to
      reproduce conduction block, increase of the maximum upstroke velocity and of the
      repolarization dispersion. None of these features can be captured by continuum
      models. In addition, the model overcomes a great disadvantage of discrete models,
      as it allows variation of the spatial resolution within a certain range. 

PMID- 26292335
TI  - Analytical Model and Optimized Design of Power Transmitting Coil for Inductively
      Coupled Endoscope Robot.
AB  - A wireless power transfer system based on the weakly inductive coupling makes it
      possible to provide the endoscope microrobot (EMR) with infinite power. To
      facilitate the patients' inspection with the EMR system, the diameter of the
      transmitting coil is enlarged to 69 cm. Due to the large transmitting range, a
      high quality factor of the Litz-wire transmitting coil is a necessity to ensure
      the intensity of magnetic field generated efficiently. Thus, this paper builds an
      analytical model of the transmitting coil, and then, optimizes the parameters of
      the coil by enlarging the quality factor. The lumped model of the transmitting
      coil includes three parameters: ac resistance, self-inductance, and stray
      capacitance. Based on the exact two-dimension solution, the accurate analytical
      expression of ac resistance is derived. Several transmitting coils of different
      specifications are utilized to verify this analytical expression, being in good
      agreements with the measured results except the coils with a large number of
      strands. Then, the quality factor of transmitting coils can be well predicted
      with the available analytical expressions of self- inductance and stray
      capacitance. Owing to the exact estimation of quality factor, the appropriate
      coil turns of the transmitting coil is set to 18-40 within the restrictions of
      transmitting circuit and human tissue issues. To supply enough energy for the
      next generation of the EMR equipped with a O9.5*10.1 mm receiving coil, the coil
      turns of the transmitting coil is optimally set to 28, which can transfer a
      maximum power of 750 mW with the remarkable delivering efficiency of 3.55%.

PMID- 26292336
TI  - Convex-Optimization-Based Compartmental Pharmacokinetic Analysis for Prostate
      Tumor Characterization Using DCE-MRI.
AB  - Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a powerful
      imaging modality to study the pharmacokinetics in a suspected cancer/tumor
      tissue. The pharmacokinetic (PK) analysis of prostate cancer includes the
      estimation of time activity curves (TACs), and thereby, the corresponding kinetic
      parameters (KPs), and plays a pivotal role in diagnosis and prognosis of prostate
      cancer. In this paper, we endeavor to develop a blind source separation
      algorithm, namely convex-optimization-based KPs estimation (COKE) algorithm for
      PK analysis based on compartmental modeling of DCE-MRI data, for effective
      prostate tumor detection and its quantification. The COKE algorithm first
      identifies the best three representative pixels in the DCE-MRI data,
      corresponding to the plasma, fast-flow, and slow-flow TACs, respectively. The
      estimation accuracy of the flux rate constants (FRCs) of the fast-flow and slow
      flow TACs directly affects the estimation accuracy of the KPs that provide the
      cancer and normal tissue distribution maps in the prostate region. The COKE
      algorithm wisely exploits the matrix structure (Toeplitz, lower triangular, and
      exponential decay) of the original nonconvex FRCs estimation problem, and
      reformulates it into two convex optimization problems that can reliably estimate
      the FRCs. After estimation of the FRCs, the KPs can be effectively estimated by
      solving a pixel-wise constrained curve-fitting (convex) problem. Simulation
      results demonstrate the efficacy of the proposed COKE algorithm. The COKE
      algorithm is also evaluated with DCE-MRI data of four different patients with
      prostate cancer and the obtained results are consistent with clinical
      observations. 

PMID- 26292334
TI  - A Review of Emerging Technologies for the Management of Diabetes Mellitus.
AB  - OBJECTIVE: High prevalence of diabetes mellitus (DM) along with the poor health
      outcomes and the escalated costs of treatment and care poses the need to focus on
      prevention, early detection and improved management of the disease. The aim of
      this paper is to present and discuss the latest accomplishments in sensors for
      glucose and lifestyle monitoring along with clinical decision support systems
      (CDSSs) facilitating self-disease management and supporting healthcare
      professionals in decision making. METHODS: A critical literature review analysis
      is conducted focusing on advances in: 1) sensors for physiological and lifestyle
      monitoring, 2) models and molecular biomarkers for predicting the onset and
      assessing the progress of DM, and 3) modeling and control methods for regulating
      glucose levels. RESULTS: Glucose and lifestyle sensing technologies are
      continuously evolving with current research focusing on the development of
      noninvasive sensors for accurate glucose monitoring. A wide range of modeling,
      classification, clustering, and control approaches have been deployed for the
      development of the CDSS for diabetes management. Sophisticated multiscale,
      multilevel modeling frameworks taking into account information from behavioral
      down to molecular level are necessary to reveal correlations and patterns
      indicating the onset and evolution of DM. CONCLUSION: Integration of data
      originating from sensor-based systems and electronic health records combined with
      smart data analytics methods and powerful user centered approaches enable the
      shift toward preventive, predictive, personalized, and participatory diabetes
      care. SIGNIFICANCE: The potential of sensing and predictive modeling approaches
      toward improving diabetes management is highlighted and related challenges are
      identified.

PMID- 26292337
TI  - Reverse-Time Migration Based Optical Imaging.
AB  - We theoretically demonstrated a new optical imaging technique based on reverse
      time migration (RTM) for reconstructing optical structures in homogeneous media
      for the first time. RTM is a powerful wave-equation-based method to reconstruct
      the image of the structure by modeling the wave propagation inside the media with
      both forward modeling and reverse-time extrapolation. While RTM is commonly used
      with acoustic seismic waves, this paper represents the first effort to develop
      optical RTM imaging method for biomedical research. To refine the image quality,
      we further developed new methods to suppress the low-wavenumber artifact (LWA).
      When compared with the conventional means for LWA suppression such as Laplacian
      filtering, illumination normalization, and the ratio method, our new derivative
      based and power-image methods are able to significantly reduce LWA, resulting in
      high-quality reconstructed images with sufficient contrasts and spatial
      resolutions for structure identification. The optical RTM imaging technique may
      provide a new platform for non-invasive optical imaging of structures in deep
      layers of tissues for biomedical applications. 

PMID- 26292338
TI  - Dictionary-Driven Ischemia Detection From Cardiac Phase-Resolved Myocardial BOLD
      MRI at Rest.
AB  - Cardiac Phase-resolved Blood-Oxygen-Level Dependent (CP-BOLD) MRI provides a
      unique opportunity to image an ongoing ischemia at rest. However, it requires
      post-processing to evaluate the extent of ischemia. To address this, here we
      propose an unsupervised ischemia detection (UID) method which relies on the
      inherent spatio-temporal correlation between oxygenation and wall motion to
      formalize a joint learning and detection problem based on dictionary
      decomposition. Considering input data of a single subject, it treats ischemia as
      an anomaly and iteratively learns dictionaries to represent only normal
      observations (corresponding to myocardial territories remote to ischemia).
      Anomaly detection is based on a modified version of One-class Support Vector
      Machines (OCSVM) to regulate directly the margins by incorporating the dictionary
      based representation errors. A measure of ischemic extent (IE) is estimated,
      reflecting the relative portion of the myocardium affected by ischemia. For
      visualization purposes an ischemia likelihood map is created by estimating
      posterior probabilities from the OCSVM outputs, thus obtaining how likely the
      classification is correct. UID is evaluated on synthetic data and in a 2D CP-BOLD
      data set from a canine experimental model emulating acute coronary syndromes.
      Comparing early ischemic territories identified with UID against infarct
      territories (after several hours of ischemia), we find that IE, as measured by
      UID, is highly correlated (Pearson's r=0.84) with respect to infarct size. When
      advances in automated registration and segmentation of CP-BOLD images and full
      coverage 3D acquisitions become available, we hope that this method can enable
      pixel-level assessment of ischemia with this truly non-invasive imaging
      technique. 

PMID- 26292339
TI  - Structure Tensor Based Analysis of Cells and Nuclei Organization in Tissues.
AB  - Extracting geometrical information from large 2D or 3D biomedical images is
      important to better understand fundamental phenomena such as morphogenesis. We
      address the problem of automatically analyzing spatial organization of cells or
      nuclei in 2D or 3D images of tissues. This problem is challenging due to the
      usually low quality of microscopy images as well as their typically large sizes.
      The structure tensor is a simple and robust descriptor that was developed to
      analyze textures orientation. Contrarily to segmentation methods which rely on an
      object based modeling of images, the structure tensor considers the sample at a
      macroscopic scale, like a continuous medium. We show that this tool allows
      quantifying two important features of nuclei in tissues: their privileged
      orientation as well as the ratio between the length of their main axes. A
      quantitative evaluation of the method is provided for synthetic and real 2D and
      3D images. As an application, we analyze the nuclei orientation and anisotropy on
      multicellular tumor spheroids cryosections. This analysis reveals that cells are
      elongated in a privileged direction that is parallel to the spheroid boundary. A
      MATLAB toolbox and an Icy plugin are available to use the proposed method. 

PMID- 26292340
TI  - Local Multi-Grouped Binary Descriptor With Ring-Based Pooling Configuration and
      Optimization.
AB  - Local binary descriptors are attracting increasingly attention due to their great
      advantages in computational speed, which are able to achieve real-time
      performance in numerous image/vision applications. Various methods have been
      proposed to learn data-dependent binary descriptors. However, most existing
      binary descriptors aim overly at computational simplicity at the expense of
      significant information loss which causes ambiguity in similarity measure using
      Hamming distance. In this paper, by considering multiple features might share
      complementary information, we present a novel local binary descriptor, referred
      as ring-based multi-grouped descriptor (RMGD), to successfully bridge the
      performance gap between current binary and floated-point descriptors. Our
      contributions are twofold. First, we introduce a new pooling configuration based
      on spatial ring-region sampling, allowing for involving binary tests on the full
      set of pairwise regions with different shapes, scales, and distances. This leads
      to a more meaningful description than the existing methods which normally apply a
      limited set of pooling configurations. Then, an extended Adaboost is proposed for
      an efficient bit selection by emphasizing high variance and low correlation,
      achieving a highly compact representation. Second, the RMGD is computed from
      multiple image properties where binary strings are extracted. We cast multi
      grouped features integration as rankSVM or sparse support vector machine learning
      problem, so that different features can compensate strongly for each other, which
      is the key to discriminativeness and robustness. The performance of the RMGD was
      evaluated on a number of publicly available benchmarks, where the RMGD
      outperforms the state-of-the-art binary descriptors significantly. 

PMID- 26292341
TI  - Image Outlier Detection and Feature Extraction via L1-Norm-Based 2D Probabilistic
      PCA.
AB  - This paper introduces an L1-norm-based probabilistic principal component analysis
      model on 2D data (L1-2DPPCA) based on the assumption of the Laplacian noise
      model. The Laplacian or L1 density function can be expressed as a superposition
      of an infinite number of Gaussian distributions. Under this expression, a
      Bayesian inference can be established based on the variational expectation
      maximization approach. All the key parameters in the probabilistic model can be
      learned by the proposed variational algorithm. It has experimentally been
      demonstrated that the newly introduced hidden variables in the superposition can
      serve as an effective indicator for data outliers. Experiments on some publicly
      available databases show that the performance of L1-2DPPCA has largely been
      improved after identifying and removing sample outliers, resulting in more
      accurate image reconstruction than the existing PCA-based methods. The
      performance of feature extraction of the proposed method generally outperforms
      other existing algorithms in terms of reconstruction errors and classification
      accuracy. 

PMID- 26292342
TI  - Subjective and Objective Video Quality Assessment of 3D Synthesized Views With
      Texture/Depth Compression Distortion.
AB  - The quality assessment for synthesized video with texture/depth compression
      distortion is important for the design, optimization, and evaluation of the multi
      view video plus depth (MVD)-based 3D video system. In this paper, the subjective
      and objective studies for synthesized view assessment are both conducted. First,
      a synthesized video quality database with texture/depth compression distortion is
      presented with subjective scores given by 56 subjects. The 140 videos are
      synthesized from ten MVD sequences with different texture/depth quantization
      combinations. Second, a full reference objective video quality assessment (VQA)
      method is proposed concerning about the annoying temporal flicker distortion and
      the change of spatio-temporal activity in the synthesized video. The proposed VQA
      algorithm has a good performance evaluated on the entire synthesized video
      quality database, and is particularly prominent on the subsets which have
      significant temporal flicker distortion induced by depth compression and view
      synthesis process. 

PMID- 26292343
TI  - Graph Matching Based on Stochastic Perturbation.
AB  - This paper presents a novel perspective on characterizing the spectral
      correspondence between the nodes of weighted graphs for image matching
      applications. The algorithm is based on the principal feature components obtained
      by stochastic perturbation of a graph. There are three areas of contributions in
      this paper. First, a stochastic normalized Laplacian matrix of a weighted graph
      is obtained by perturbing the matrix of a sensed graph model. Second, we obtain
      the eigenvectors based on an eigen-decomposition approach, where representative
      elements of each row of this matrix can be considered to be the feature
      components of a feature point. Third, correct correspondences are determined in a
      low-dimensional principal feature component space between the graphs. In order to
      further enhance image matching, we also exploit the random sample consensus
      algorithm, as a post-processing step, to eliminate mismatches in feature
      correspondences. The experiments on synthetic and real-world images demonstrate
      the effectiveness and accuracy of the proposed method. 

PMID- 26292344
TI  - A Cytomorphic Chip for Quantitative Modeling of Fundamental Bio-Molecular
      Circuits.
AB  - We describe a 0.35 MUm BiCMOS silicon chip that quantitatively models fundamental
      molecular circuits via efficient log-domain cytomorphic transistor equivalents.
      These circuits include those for biochemical binding with automatic
      representation of non-modular and loading behavior, e.g., in cascade and fan-out
      topologies; for representing variable Hill-coefficient operation and cooperative
      binding; for representing inducer, transcription-factor, and DNA binding; for
      probabilistic gene transcription with analogic representations of log-linear and
      saturating operation; for gain, degradation, and dynamics of mRNA and protein
      variables in transcription and translation; and, for faithfully representing
      biological noise via tunable stochastic transistor circuits. The use of on-chip
      DACs and ADCs enables multiple chips to interact via incoming and outgoing
      molecular digital data packets and thus create scalable biochemical reaction
      networks. The use of off-chip digital processors and on-chip digital memory
      enables programmable connectivity and parameter storage. We show that published
      static and dynamic MATLAB models of synthetic biological circuits including
      repressilators, feed-forward loops, and feedback oscillators are in excellent
      quantitative agreement with those from transistor circuits on the chip.
      Computationally intensive stochastic Gillespie simulations of molecular
      production are also rapidly reproduced by the chip and can be reliably tuned over
      the range of signal-to-noise ratios observed in biological cells.

PMID- 26292345
TI  - Image Understanding Applications of Lattice Autoassociative Memories.
AB  - Multivariate mathematical morphology (MMM) aims to extend the mathematical
      morphology from gray scale images to images whose pixels are high-dimensional
      vectors, such as remote sensing hyperspectral images and functional magnetic
      resonance images (fMRIs). Defining an ordering over the multidimensional image
      data space is a fundamental issue MMM, to ensure that ensuing morphological
      operators and filters are mathematically consistent. Recent approaches use the
      outputs of two-class classifiers to build such reduced orderings. This paper
      presents the applications of MMM built on reduced supervised orderings based on
      lattice autoassociative memories (LAAMs) recall error measured by the Chebyshev
      distance. Foreground supervised orderings use one set of training data from a
      foreground class, whereas background/foreground supervised orderings use two
      training data sets, one for each relevant class. The first case study refers to
      the realization of the thematic segmentation of the hyperspectral images using
      spatial-spectral information. Spectral classification is enhanced by a spatial
      processing consisting in the spatial correction guided by a watershed
      segmentation computed by the LAAM-based morphological operators. The approach
      improves the state-of-the-art hyperspectral spatial-spectral thematic map
      building approaches. The second case study is the analysis of resting state fMRI
      data, working on a data set of healthy controls, schizophrenia patients with and
      without auditory hallucinations. We perform two experiments: 1) the localization
      of differences in brain functional networks on population-dependent templates and
      2) the classification of subjects into each possible pair of cases. In this data
      set, we find that the LAAM-based morphological features improve over the
      conventional correlation-based graph measure features often employed in fMRI data
      classification.

PMID- 26292346
TI  - Data-Driven Zero-Sum Neuro-Optimal Control for a Class of Continuous-Time Unknown
      Nonlinear Systems With Disturbance Using ADP.
AB  - This paper is concerned with a new data-driven zero-sum neuro-optimal control
      problem for continuous-time unknown nonlinear systems with disturbance. According
      to the input-output data of the nonlinear system, an effective recurrent neural
      network is introduced to reconstruct the dynamics of the nonlinear system.
      Considering the system disturbance as a control input, a two-player zero-sum
      optimal control problem is established. Adaptive dynamic programming (ADP) is
      developed to obtain the optimal control under the worst case of the disturbance.
      Three single-layer neural networks, including one critic and two action networks,
      are employed to approximate the performance index function, the optimal control
      law, and the disturbance, respectively, for facilitating the implementation of
      the ADP method. Convergence properties of the ADP method are developed to show
      that the system state will converge to a finite neighborhood of the equilibrium.
      The weight matrices of the critic and the two action networks are also convergent
      to finite neighborhoods of their optimal ones. Finally, the simulation results
      will show the effectiveness of the developed data-driven ADP methods. 

PMID- 26292347
TI  - A Derivative-Free Riemannian Powell's Method, Minimizing Hartley-Entropy-Based
      ICA Contrast.
AB  - Even though the Hartley-entropy-based contrast function guarantees an unmixing
      local minimum, the reported nonsmooth optimization techniques that minimize this
      nondifferentiable function encounter computational bottlenecks. Toward this,
      Powell's derivative-free optimization method has been extended to a Riemannian
      manifold, namely, oblique manifold, for the recovery of quasi-correlated sources
      by minimizing this contrast function. The proposed scheme has been demonstrated
      to converge faster than the related algorithms in the literature, besides the
      impressive source separation results in simulations involving synthetic sources
      having finite-support distributions and correlated images.

PMID- 26292348
TI  - Automated Cognitive Health Assessment From Smart Home-Based Behavior Data.
AB  - Smart home technologies offer potential benefits for assisting clinicians by
      automating health monitoring and well-being assessment. In this paper, we examine
      the actual benefits of smart home-based analysis by monitoring daily behavior in
      the home and predicting clinical scores of the residents. To accomplish this
      goal, we propose a clinical assessment using activity behavior (CAAB) approach to
      model a smart home resident's daily behavior and predict the corresponding
      clinical scores. CAAB uses statistical features that describe characteristics of
      a resident's daily activity performance to train machine learning algorithms that
      predict the clinical scores. We evaluate the performance of CAAB utilizing smart
      home sensor data collected from 18 smart homes over two years. We obtain a
      statistically significant correlation ( r=0.72) between CAAB-predicted and
      clinician-provided cognitive scores and a statistically significant correlation (
      r=0.45) between CAAB-predicted and clinician-provided mobility scores. These
      prediction results suggest that it is feasible to predict clinical scores using
      smart home sensor data and learning-based data analysis.

PMID- 26292349
TI  - A Prototype of Reflection Pulse Oximeter Designed for Mobile Healthcare.
AB  - This paper introduces a pulse oximeter prototype designed for mobile healthcare.
      In this prototype, a reflection pulse oximeter is embedded into the back cover of
      a smart handheld device to offer the convenient measurement of both heart rate
      (HR) and SpO2 (estimation of arterial oxygen saturation) for home or mobile
      applications. Novel and miniaturized circuit modules including a chopper network
      and a filtering amplifier were designed to overcome the influence of ambient
      light and interferences that are caused by embedding the sensor into a flat
      cover. A method based on adaptive trough detection for improved HR and SpO2
      estimation is proposed with appropriate simplification for its implementation on
      mobile devices. A fast and effective photoplethysmogram validation scheme is also
      proposed. Clinical experiments have been carried out to calibrate and test our
      oximeter. Our prototype oximeter can achieve comparable performance to a clinical
      oximeter with no significant difference revealed by paired t -tests ( p = 0.182
      for SpO2 measurement and p = 0.496 for HR measurement). The design of this pulse
      oximeter will facilitate fast and convenient measurement of SpO2 for mobile
      healthcare.

PMID- 26292350
TI  - Contribution of a Trunk Accelerometer System to the Characterization of Gait in
      Patients With Mild-to-Moderate Parkinson's Disease.
AB  - OBJECTIVE: Gait disturbances like shuffling and short steps are obvious at visual
      observation in patients with advanced Parkinson's disease (PD). However,
      quantitative methods are increasingly used to evaluate the wide range of gait
      abnormalities that may occur over the disease course. The goal of this study was
      to test the ability of a trunk accelerometer system to quantify the effects of PD
      on several gait features when walking at self-selected speed. METHODS: We
      recruited 96 subjects split into three age-matched groups: 32 healthy controls
      (HC), 32 PD patients at Hoehn and Yahr stage < II (PD-1), and 32 patients at
      Hoehn and Yahr stage II-III (PD-2). The following outcomes were extracted from
      the signals of the triaxial accelerometer worn on the lower back: stride length,
      cadence, regularity index, symmetry index, and mechanical powers yielded in the
      cranial-caudal, anteroposterior, and medial-lateral directions. Walking speed was
      measured using a stopwatch. RESULTS: Besides other gait features, the PD-1 and
      the PD-2 groups showed significantly reduced stride length normalized to height
      (p < 0.02) and symmetry index (p < 0.009) in comparison to the HC. Regularity
      index was the only feature significantly decreased in the PD-2 group as compared
      with the two other groups (p < 0.01). The clinical relevance of this finding was
      supported by significant correlations with mobility and gait scales (r is around 
      0.3; p < 0.05). CONCLUSION: Gait quantified by a trunk accelerometer may provide
      clinically useful information for the screening and follow-up of PD patients.

PMID- 26292351
TI  - W2E--Wellness Warehouse Engine for Semantic Interoperability of Consumer Health
      Data.
AB  - Novel health monitoring devices and applications allow consumers easy and
      ubiquitous ways to monitor their health status. However, technologies from
      different providers lack both technical and semantic interoperability and hence
      the resulting health data are often deeply tied to a specific service, which is
      limiting its reusability and utilization in different services. We have designed
      a Wellness Warehouse Engine (W2E) that bridges this gap and enables seamless
      exchange of data between different services. W2E provides interfaces to various
      data sources and makes data available via unified representational state transfer
      application programming interface to other services. Importantly, it includes
      Unifier--an engine that allows transforming input data into generic units
      reusable by other services, and Analyzer--an engine that allows advanced analysis
      of input data, such as combining different data sources into new output
      parameters. In this paper, we describe the architecture of W2E and demonstrate
      its applicability by using it for unifying data from four consumer activity
      trackers, using a test base of 20 subjects each carrying out three different
      tracking sessions. Finally, we discuss challenges of building a scalable Unifier
      engine for the ever-enlarging number of new devices.

PMID- 26292352
TI  - A Memetic Algorithm for Global Optimization of Multimodal Nonseparable Problems.
AB  - It is a big challenging issue of avoiding falling into local optimum especially
      when facing high-dimensional nonseparable problems where the interdependencies
      among vector elements are unknown. In order to improve the performance of
      optimization algorithm, a novel memetic algorithm (MA) called cooperative
      particle swarm optimizer-modified harmony search (CPSO-MHS) is proposed in this
      paper, where the CPSO is used for local search and the MHS for global search. The
      CPSO, as a local search method, uses 1-D swarm to search each dimension
      separately and thus converges fast. Besides, it can obtain global optimum
      elements according to our experimental results and analyses. MHS implements the
      global search by recombining different vector elements and extracting global
      optimum elements. The interaction between local search and global search creates
      a set of local search zones, where global optimum elements reside within the
      search space. The CPSO-MHS algorithm is tested and compared with seven other
      optimization algorithms on a set of 28 standard benchmarks. Meanwhile, some MAs
      are also compared according to the results derived directly from their
      corresponding references. The experimental results demonstrate a good performance
      of the proposed CPSO-MHS algorithm in solving multimodal nonseparable problems.

PMID- 26292353
TI  - Learning A Superpixel-Driven Speed Function for Level Set Tracking.
AB  - A key problem in level set tracking is to construct a discriminative speed
      function for effective contour evolution. In this paper, we propose a level set
      tracking method based on a discriminative speed function, which produces a
      superpixel-driven force for effective level set evolution. Based on kernel
      density estimation and metric learning, the speed function is capable of
      effectively encoding the discriminative information on object appearance within a
      feasible metric space. Furthermore, we introduce adaptive object shape modeling
      into the level set evolution process, which leads to the tracking robustness in
      complex scenarios. To ensure the efficiency of adaptive object shape modeling, we
      develop a simple but efficient weighted non-negative matrix factorization method
      that can online learn an object shape dictionary. Experimental results on a
      number of challenging video sequences demonstrate the effectiveness and
      robustness of the proposed tracking method.

PMID- 26292354
TI  - Distributed Consensus of Stochastic Delayed Multi-agent Systems Under
      Asynchronous Switching.
AB  - In this paper, the distributed exponential consensus of stochastic delayed multi
      agent systems with nonlinear dynamics is investigated under asynchronous
      switching. The asynchronous switching considered here is to account for the time
      of identifying the active modes of multi-agent systems. After receipt of
      confirmation of mode's switching, the matched controller can be applied, which
      means that the switching time of the matched controller in each node usually lags
      behind that of system switching. In order to handle the coexistence of switched
      signals and stochastic disturbances, a comparison principle of stochastic
      switched delayed systems is first proved. By means of this extended comparison
      principle, several easy to verified conditions for the existence of an
      asynchronously switched distributed controller are derived such that stochastic
      delayed multi-agent systems with asynchronous switching and nonlinear dynamics
      can achieve global exponential consensus. Two examples are given to illustrate
      the effectiveness of the proposed method.

PMID- 26292355
TI  - Robotic Billiards: Understanding Humans in Order to Counter Them.
AB  - Ongoing technological advances in the areas of computation, sensing, and
      mechatronics enable robotic-based systems to interact with humans in the real
      world. To succeed against a human in a competitive scenario, a robot must
      anticipate the human behavior and include it in its own planning framework. Then
      it can predict the next human move and counter it accordingly, thus not only
      achieving overall better performance but also systematically exploiting the
      opponent's weak spots. Pool is used as a representative scenario to derive a
      model-based planning and control framework where not only the physics of the
      environment but also a model of the opponent is considered. By representing the
      game of pool as a Markov decision process and incorporating a model of the human
      decision-making based on studies, an optimized policy is derived. This enables
      the robot to include the opponent's typical game style into its tactical
      considerations when planning a stroke. The results are validated in simulations
      and real-life experiments with an anthropomorphic robot playing pool against a
      human.

PMID- 26292356
TI  - Dynamic Behavior of Artificial Hodgkin-Huxley Neuron Model Subject to Additive
      Noise.
AB  - Motivated by neuroscience discoveries during the last few years, many studies
      consider pulse-coupled neural networks with spike-timing as an essential
      component in information processing by the brain. There also exists some
      technical challenges while simulating the networks of artificial spiking neurons.
      The existing studies use a Hodgkin-Huxley (H-H) model to describe spiking
      dynamics and neuro-computational properties of each neuron. But they fail to
      address the effect of specific non-Gaussian noise on an artificial H-H neuron
      system. This paper aims to analyze how an artificial H-H neuron responds to add
      different types of noise using an electrical current and subunit noise model. The
      spiking and bursting behavior of this neuron is also investigated through
      numerical simulations. In addition, through statistic analysis, the intensity of
      different kinds of noise distributions is discussed to obtain their relationship
      with the mean firing rate, interspike intervals, and stochastic resonance. 

PMID- 26292357
TI  - A Multistage Approach for Image Registration.
AB  - Successful image registration is an important step for object recognition, target
      detection, remote sensing, multimodal content fusion, scene blending, and
      disaster assessment and management. The geometric and photometric variations
      between images adversely affect the ability for an algorithm to estimate the
      transformation parameters that relate the two images. Local deformations,
      lighting conditions, object obstructions, and perspective differences all
      contribute to the challenges faced by traditional registration techniques. In
      this paper, a novel multistage registration approach is proposed that is
      resilient to view point differences, image content variations, and lighting
      conditions. Robust registration is realized through the utilization of a novel
      region descriptor which couples with the spatial and texture characteristics of
      invariant feature points. The proposed region descriptor is exploited in a
      multistage approach. A multistage process allows the utilization of the graph
      based descriptor in many scenarios thus allowing the algorithm to be applied to a
      broader set of images. Each successive stage of the registration technique is
      evaluated through an effective similarity metric which determines subsequent
      action. The registration of aerial and street view images from pre- and post
      disaster provide strong evidence that the proposed method estimates more accurate
      global transformation parameters than traditional feature-based methods.
      Experimental results show the robustness and accuracy of the proposed multistage
      image registration methodology. 

PMID- 26292358
TI  - Visual Tracking via Random Walks on Graph Model.
AB  - In this paper, we formulate visual tracking as random walks on graph models with
      nodes representing superpixels and edges denoting relationships between
      superpixels. We integrate two novel graphs with the theory of Markov random
      walks, resulting in two Markov chains. First, an ergodic Markov chain is enforced
      to globally search for the candidate nodes with similar features to the template
      nodes. Second, an absorbing Markov chain is utilized to model the temporal
      coherence between consecutive frames. The final confidence map is generated by a
      structural model which combines both appearance similarity measurement derived by
      the random walks and internal spatial layout demonstrated by different target
      parts. The effectiveness of the proposed Markov chains as well as the structural
      model is evaluated both qualitatively and quantitatively. Experimental results on
      challenging sequences show that the proposed tracking algorithm performs
      favorably against state-of-the-art methods. 

PMID- 26292361
TI  - Cell-of-Origin of Cancer versus Cancer Stem Cells: Assays and Interpretations.
AB  - A tumor originates from a normal cell that has undergone tumorigenic
      transformation as a result of genetic mutations. This transformed cell is the
      cell-of-origin for the tumor. In contrast, an established clinical tumor is
      sustained by subpopulations of self-renewing cancer cells operationally called
      cancer stem cells (CSC) that can generate, intraclonally, both tumorigenic and
      nontumorigenic cells. Identifying and characterizing tumor cell-of-origin and
      CSCs should help elucidate tumor cell heterogeneity, which, in turn, should help
      understand tumor cell responses to clinical treatments, drug resistance, tumor
      relapse, and metastatic spread. Both tumor transplantation and lineage-tracing
      assays have been helpful in characterizing these cancer cell populations,
      although each system has its strengths and caveats. In this article, we briefly
      review and summarize advantages and limitations of both assays in support of a
      combinatorial approach to accurately define the roles of both cancer-initiating
      and cancer-propagating cells. As an aside, we also wish to clarify the
      definitions of cancer cell-of-origin and CSCs, which are often interchangeably
      used by mistake.

PMID- 26292363
TI  - Correction for Aguilar et al., The P25 Protein of Potato Virus X (PVX) Is the
      Main Pathogenicity Determinant Responsible for Systemic Necrosis in PVX
      Associated Synergisms.

PMID- 26292365
TI  - VITAMINES. 1915.

PMID- 26292366
TI  - Final Priority. Rehabilitation Training: Vocational Rehabilitation Workforce
      Innovation Technical Assistance Center. Final priority.
AB  - The Assistant Secretary for Special Education and Rehabilitative Services
      announces a priority under the Rehabilitation Training program. The Assistant
      Secretary may use this priority for competitions in fiscal year 2015 and later
      years. We take this action to provide training and technical assistance to State
      vocational rehabilitation agencies to improve services under the State Vocational
      Rehabilitation Services program and State Supported Employment Services program
      for individuals with disabilities, including those with the most significant
      disabilities, and to implement changes to the Rehabilitation Act of 1973, as
      amended by the Workforce Innovation and Opportunity Act (WIOA), signed into law
      on July 22, 2014.

PMID- 26292367
TI  - Additional Compensation on Account of Children Adopted Out of   Veteran's Family.
      Final rule.
AB  - The Department of Veterans Affairs (VA) is amending its adjudication regulations
      to clarify that a veteran will not receive the dependent rate of disability
      compensation for a child who is adopted out of the veteran's family. This action
      is necessary because applicable VA adjudication regulations are currently
      construed as permitting a veteran, whose former child was adopted out of the
      veteran's family, to receive the dependent rate of disability compensation for
      the adopted-out child, which constitutes an unwarranted award of benefits not
      supported by the applicable statute and legislative history. This document adopts
      as a final rule, without change, the proposed rule published in the Federal
      Register on December 2, 2014.

PMID- 26292368
TI  - Final Priority and Definitions--Rehabilitation Training: Vocational
      Rehabilitation Technical Assistance Center-Target Communities. Final priority and
      definitions.
AB  - The Assistant Secretary for Special Education and Rehabilitative Services
      announces a priority and definitions under the Rehabilitation Training program to
      fund a cooperative agreement to develop and support a Vocational Rehabilitation
      Technical Assistance Center for Targeted Communities (VRTAC-TC). The Assistant
      Secretary may use the priority and definitions for competitions in fiscal year
      (FY) 2015 and later years. We take this action to focus Federal financial
      assistance on an identified national need. We intend the VRTAC-TC to improve the
      capacity of State vocational rehabilitation (VR) agencies and their partners to
      increase participation levels for individuals with disabilities from low-income
      communities and to equip these individuals with the skills and competencies
      needed to obtain high-quality competitive integrated employment.

PMID- 26292362
TI  - DeltaNp63alpha Promotes Breast Cancer Cell Motility through the Selective
      Activation of Components of the Epithelial-to-Mesenchymal Transition Program.
AB  - Cell identity signals influence the invasive capability of tumor cells, as
      demonstrated by the selection for programs of epithelial-to-mesenchymal
      transition (EMT) during malignant progression. Breast cancer cells retain
      canonical epithelial traits and invade collectively as cohesive groups of cells,
      but the signaling pathways critical to their invasive capabilities are still
      incompletely understood. Here we report that the transcription factor
      DeltaNp63alpha drives the migration of basal-like breast cancer (BLBC) cells by
      inducing a hybrid mesenchymal/epithelial state. Through a combination of
      expression analysis and functional testing across multiple BLBC cell populations,
      we determined that DeltaNp63alpha induces migration by elevating the expression
      of the EMT program components Slug and Axl. Interestingly, DeltaNp63alpha also
      increased the expression of miR-205, which can silence ZEB1/2 to prevent the loss
      of epithelial character caused by EMT induction. In clinical specimens, co
      expression of various elements of the DeltaNp63alpha pathway confirmed its
      implication in motility signaling in BLBC. We observed that activation of the
      DeltaNp63alpha pathway occurred during the transition from noninvasive ductal
      carcinoma in situ to invasive breast cancer. Notably, in an orthotopic tumor
      model, Slug expression was sufficient to induce collective invasion of E-cadherin
      expressing BLBC cells. Together, our results illustrate how DeltaNp63alpha can
      drive breast cancer cell invasion by selectively engaging promigratory components
      of the EMT program while, in parallel, still promoting the retention of
      epithelial character.

PMID- 26292370
TI  - Animals on VA property. Final rule.
AB  - The Department of Veterans Affairs (VA) amends its regulation concerning the
      presence of animals on VA property. This final rule expands the current VA
      regulation to authorize the presence of service animals consistent with
      applicable Federal law when these animals accompany individuals with disabilities
      seeking admittance to property owned or operated by VA.

PMID- 26292369
TI  - Medical Devices; Neurological Devices; Classification of the   Computerized
      Cognitive Assessment Aid. Final order.
AB  - The Food and Drug Administration (FDA) is classifying the computerized cognitive
      assessment aid into class II (special controls). The special controls that will
      apply to the device are identified in this order, and will be part of the
      codified language for the computerized cognitive assessment aid's classification.
      The Agency is classifying the device into class II (special controls) in order to
      provide a reasonable assurance of safety and effectiveness of the device.

PMID- 26292371
TI  - Medicare Program; Hospital Inpatient Prospective Payment Systems for Acute Care
      Hospitals and the Long-Term Care Hospital Prospective Payment System Policy
      Changes and Fiscal Year 2016 Rates; Revisions of Quality Reporting Requirements
      for Specific Providers, Including Changes Related to the Electronic Health Record
      Incentive Program; Extensions of the Medicare-Dependent, Small Rural Hospital
      Program and the Low-Volume Payment Adjustment for Hospitals. Final rule; interim
      final rule with comment period.
AB  - We are revising the Medicare hospital inpatient prospective payment systems
      (IPPS) for operating and capital related costs of acute care hospitals to
      implement changes arising from our continuing experience with these systems for
      FY 2016. Some of these changes implement certain statutory provisions contained
      in the Patient Protection and Affordable Care Act and the Health Care and
      Education Reconciliation Act of 2010 (collectively known as the Affordable Care
      Act), the Pathway for Sustainable Growth Reform(SGR) Act of 2013, the Protecting
      Access to Medicare Act of 2014, the Improving Medicare Post-Acute Care
      Transformation Act of 2014, the Medicare Access and CHIP Reauthorization Act of
      2015, and other legislation. We also are addressing the update of the rate-of
      increase limits for certain hospitals excluded from the IPPS that are paid on a
      reasonable cost basis subject to these limits for FY 2016.As an interim final
      rule with comment period, we are implementing the statutory extensions of the
      Medicare dependent,small rural hospital (MDH)Program and changes to the payment
      adjustment for low-volume hospitals under the IPPS.We also are updating the
      payment policies and the annual payment rates for the Medicare prospective
      payment system (PPS) for inpatient hospital services provided by long-term care
      hospitals (LTCHs) for FY 2016 and implementing certain statutory changes to the
      LTCH PPS under the Affordable Care Act and the Pathway for Sustainable Growth
      Rate (SGR) Reform Act of 2013 and the Protecting Access to Medicare Act of
      2014.In addition, we are establishing new requirements or revising existing
      requirements for quality reporting by specific providers (acute care
      hospitals,PPS-exempt cancer hospitals, and LTCHs) that are participating in
      Medicare, including related provisions for eligible hospitals and critical access
      hospitals participating in the Medicare Electronic Health Record (EHR)Incentive
      Program. We also are updating policies relating to the Hospital Value-Based
      Purchasing (VBP) Program, the Hospital Readmissions Reduction Program, and the
      Hospital-Acquired Condition (HAC) Reduction Program.

PMID- 26292372
TI  - Medical Devices; Cardiovascular Devices; Classification of the Esophageal Thermal
      Regulation Device. Final order.
AB  - The Food and Drug Administration (FDA) is classifying the esophageal thermal
      regulation device into class II (special controls). The special controls that
      will apply to the device are identified in this order and will be part of the
      codified language for the esophageal thermal regulation device's classification.
      The Agency is classifying the device into class II (special controls) in order to
      provide a reasonable assurance of safety and effectiveness of the device.

PMID- 26292373
TI  - Designating Additions to the Current List of Tropical Diseases in   the Federal
      Food, Drug, and Cosmetic Act. Final order.
AB  - The Federal Food, Drug, and Cosmetic Act (the FD&C Act) authorizes the Food and
      Drug Administration (FDA or Agency) to award priority review vouchers (PRVs) to
      tropical disease product applicants when the applications meet certain criteria.
      The FD&C Act lists the diseases that are considered to be tropical diseases for
      purposes of obtaining PRVs, and also provides for Agency expansion of that list
      to include other diseases that satisfy the definition of ''tropical diseases'' as
      set forth in the FD&C Act. FDA has determined that Chagas disease and
      neurocysticercosis satisfy this definition, and therefore is adding them to the
      list of designated tropical diseases whose product applications may result in the
      award of PRVs. Sponsors submitting certain applications for the treatment of
      Chagas disease and neurocysticercosis may be eligible to receive a PRV if such
      applications are approved by FDA.

PMID- 26292374
TI  - Resident Rounds: Part III - Case Report: A Non-Syndromic Case of  Multiple
      Unilateral Nodular and Pigmented Basal Cell Carcinomas.
AB  - Although basal cell carcinomas (BCC) are relatively common, particularly in older
      individuals, the development of multiple BCCs at a young age can indicate an
      associated genetic disorder. Several cases of unilateral or segmental BCCs have
      been described in the literature. Some cases have demonstrated concomitant
      syndromic findings while others had unilateral BCCs as the only finding. Herein
      we present a non-syndromic case of multiple unilateral nodular and pigmented BCCs
      in a 61-year-old Hispanic man.

PMID- 26292375
TI  - [Discussion].

PMID- 26292376
TI  - [Discussion].

PMID- 26292377
TI  - [Discussion].

PMID- 26292378
TI  - OUT OF BOUNDS. Using sports as a vehicle for positive change.

PMID- 26292379
TI  - CAN HEPATITIS C BE SEXUALLY TRANSMITTED? Yes. No. Maybe. It's complicated. All of
      the above.

PMID- 26292380
TI  - BLACK; GIFTED, AND WHOLE. The story of a fallen figure in the fight against HIV
      continues to affect us.

PMID- 26292382
TI  - Foreword to the Centenary Edition.

PMID- 26292381
TI  - A NEW TRIPLE THREAT AGAINST THE VIRUS.

PMID- 26292383
TI  - The UK maritime Role 3 medical treatment facility: the Primary Casualty Receiving
      Facility, RFA ARGUS.

PMID- 26292384
TI  - 100 Year Foreword.

PMID- 26292386
TI  - A Royal Marine Company Commander's view of the medical provision in the Falklands
      War.

PMID- 26292385
TI  - Action Stations! 100 years of trauma care on maritime and amphibious operations
      in the Royal Navy.
AB  - Over the past century trauma care within the Royal Navy (RN) has evolved; wartime
      experiences and military medical research have combined to allow significant
      improvement in the care of casualties. This article describes the key maritime
      and amphibious operations that have seen the Royal Navy Medical Service (RNMS)
      deliver high levels of support to wherever the Naval Service has deployed in the
      last 100 years. Key advancements in which progress has led to improved outcomes
      for injured personnel are highlighted--the control and treatment of blood loss,
      wound care, and the prevention and management of organ failure with optimal
      resuscitation. Historians often point out how slowly military medicine progressed
      for the first few thousand years of its recorded history, and how quickly it has
      progressed in the last century. This reflective article will show how the RNMS
      has been an integral part of that story, and how the lessons learnt by our
      predecessors have shaped our modern day doctrine surrounding trauma care.

PMID- 26292387
TI  - The Ship's Doctor in the Royal Navy--100 years of tradition and progress.
AB  - The changing role of the Senior Service over the past century through numerous
      militarily heterogeneous environments and operations has necessitated an
      evolution in the role of the deployed Medical Officer. However: versatility,
      specialist knowledge, caring for a wide and varied patient population of friendly
      and enemy forces, and the dual role of being an officer as well as a doctor, have
      remained consistent. Identifiable changes in military medical officer training,
      the shape of the Defence Medical Services, and modern advances in treatment and
      communication have evolved the Ship's Doctor role from the pre-Second World War
      setting of a contracted Naval Medical Service, through growth, to a shrinking
      cadre again in a return to the contingency operations of today. Still, the role
      today remains attractive to a subset of doctors looking for something more from
      their medical practice; as the nature of conflict changes, so too will the role
      of the Ship's Doctor. The ongoing requirement for flexibility and versatility
      will remain. Medical Officers will continue to meet the need to provide high
      quality care to their patients and, as has always been the case, will continue to
      be drawn to the Service's principal appeal of an exciting world-wide role with
      the potential for unique experiences.

PMID- 26292388
TI  - 100 Years of British military neurosurgery: on the shoulders of giants.
AB  - Death from head injuries has been a feature of conflicts throughout the world for
      centuries. The burden of mortality has been variously affected by the evolution
      in weaponry from war-hammers to explosive ordnance, the influence of armour on
      survivability and the changing likelihood of infection as a complicating factor.
      Surgery evolved from haphazard trephination to valiant, yet disjointed,
      neurosurgery by a variety of great historical surgeons until the Crimean War of
      1853-1856. However, it was events initiated by the Great War of 1914-1918 that
      not only marked the development of modern neurosurgical techniques, but our
      approach to military surgery as a whole. Here the author describes how 100 years
      of conflict and the input and intertwining relationships between the 20th
      century's great neurosurgeons established neurosurgery in the United Kingdom and
      beyond.

PMID- 26292389
TI  - The Royal Naval surgeons in the battle of Coronel.

PMID- 26292390
TI  - Commentary on "Penicillin". 1945.

PMID- 26292391
TI  - James Lind--the father of maritime medicine.

PMID- 26292392
TI  - The end for the 'Roman Sandal': an observational study of methods of securing
      chest drains in a deployed military setting.
AB  - INTRODUCTION: There is ongoing debate regarding the optimal method of securing
      chest drains in trauma patients. Various courses describe methods for chest drain
      insertion, but little has been published to identify the best method to secure
      the drain. AIM: This article aims to examine differences in approach to securing
      chest drains and the security of the methods used. METHOD: Whilst in a deployed
      medical treatment facility, 26 clinicians from various specialties and
      nationalities were asked to secure a pre-placed drain. A 32F drain was placed in
      a manikin and the clinicians were given a chance to prepare their equipment. They
      were given a choice of suture and their attempts were observed by one of the
      researchers. The attempts were timed and photographed. A second researcher, who
      had not observed the technique, then assessed the security of the drain. RESULTS:
      15/26 clinicians used a 'Roman Sandal' technique with 5/26 proving to be
      insecure. Other techniques used showed no failure. The rate of consultant-secured
      failure was 12.5% compared to 40% for registrars and 33% for General Duties
      Medical Officers. CONCLUSIONS: The type of suture used made no difference, but
      the traditional 'Roman Sandal' method was insecure. Knots tied close to the skin
      and those that bit into the drain were shown to be most effective.

PMID- 26292393
TI  - The current thinking on colorectal cancer.
AB  - Colorectal cancer (CRC) is the fourth most common cancer in the UK and the
      incidence has increased over recent decades. Although only 1.5% of cases are
      diagnosed in those aged under 40 years, it remains an important condition to be
      aware of in the military population. Patients who are genetically predisposed can
      have a lifetime risk of 80-100% of developing CRC and are likely to develop
      symptoms during their service. 20% of patients will present with metastatic
      disease. While surgical and oncological treatments have improved outcomes, early
      diagnosis of CRC is essential to reducing mortality. This paper provides an
      overview of the aetiology, investigations and treatment options for CRC.
      Explanation of primary surgical options and the principles of adjuvant therapies
      are included to aid informed discussions with patients.

PMID- 26292394
TI  - The early management of the burned patient in the Naval service.
AB  - Burns represent a perpetual threat in military combat and are a pervasive threat
      in the land, maritime and air arenas. Therefore, it is imperative that military
      clinicians are well versed in managing burns in order to ensure optimal survival
      and recovery. This article aims to explore the epidemiology, pathophysiology,
      assessment and early management of the burned patient with a focus on the austere
      maritime environment and current military guidance.

PMID- 26292395
TI  - Meningitis in service-age personnel.
AB  - The incidence of meningitis is declining in the UK population largely due to
      increased availability of vaccinations against the most common bacterial strains.
      Acute bacterial meningitis, however, is a life-threatening condition and
      distinguishing it from more benign causes of headache and fever is difficult in
      an operational environment due to limited access to diagnostic tests. Despite
      medical advances, the case fatality rate in the United Kingdom in adults with
      invasive meningococcal disease is 10.5%. Acute bacterial meningitis presents with
      the classical triad of fever, neck pain and altered mental state in less than
      half of adults, and in the initial course of the disease it frequently mimics
      common viral illnesses. The aim of this article is to discuss the recognition and
      management of meningitis with special emphasis on the deployed military
      environment.

PMID- 26292396
TI  - Acute tonsillitis and its complications: an overview.
AB  - Acute tonsillitis may be defined as inflammation of the tonsils, predominantly
      due to infection. It is part of the spectrum of pharyngitis, which ranges from
      localised tonsillar infection to generalised infection of the pharynx and
      commonly affects young healthy adults. Simple sore throats secondary to viral or
      bacterial pharyngitis are very common and generally do not require hospital
      admission or antimicrobial treatment. Supportive management in the form of
      analgesia and adequate hydration is often sufficient. However, there is potential
      for life-threatening complications to develop, highlighting the need for basic
      knowledge in the management of these conditions. This article aims to provide an
      overview of acute tonsillitis and its complications, including peritonsillar and
      parapharyngeal abscess formation. Specific attention will be given to the
      pathogenesis, diagnosis, investigation and management of each condition, in
      particular advising on emergency pre-shore treatment and indications for referral
      to an Ear, Nose and Throat Department. We will also summarise important
      guidelines and evidence from the literature to support these management
      decisions.

PMID- 26292397
TI  - The interpretation and management of abnormal liver function tests.
AB  - Liver function tests (LFTs) are frequently requested as part of routine health
      assessments on serving members of the Royal Navy (RN). In common with many
      investigations there are a number of abnormal results in healthy individuals (0.5
      - 9% depending on test and study population). There are established patterns of
      LFT derangement such as cholestatic derangement, hepatocellular derangement, and
      failure of synthetic function. There can be indicators to the cause of the
      derangement by assessing the ratios of elevated assays in relation to one
      another. This article aims to address the definition, potential causes and
      further investigation of common patterns of LFT derangement found in primary care
      in the RN.

PMID- 26292398
TI  - The diagnosis and management of insomnia in the United Kingdom Armed Forces.
AB  - Insomnia is a common condition among patients presenting to primary care
      facilities in both civilian and military populations. This article considers the
      diagnosis, management and clinical considerations of managing this condition,
      along with the occupational and operational considerations for the United Kingdom
      Armed Forces.

PMID- 26292399
TI  - Surgeon Rear Admiral (D) David A Coppock CB OSt J.

PMID- 26292400
TI  - [Several important advances on chromatographic experiment and application in
      early 2015].

PMID- 26292401
TI  - [Application of coating technology in capillary electrophoresis for chiral
      separation].
AB  - Chirality is one of the intrinsic attributes of the nature. Chiral separation and
      analysis are of great importance in many research fields, such as life science,
      environmental science, biological engineering and pharmaceutical engineering.
      Currently, chiral capillary electrophoresis technique used for the
      enantioselective resolution of different kinds of racemates has become one of the
      most distinctive research and application fields. However, the adsorption of the
      analytes (or chiral selectors) on the inner wall of the capillary is a common
      problem in capillary electrophoresis chiral separation. Coating technology,
      namely modification of the inner wall of the capillary, is the simplest and most
      effective way to suppress disadvantageous adsorption, and to improve the
      separation efficiency and analysis repeatability. In this review, the recent
      applications of different coating procedures in chiral analysis are presented,
      and the future developments in this field are also prospected.

PMID- 26292403
TI  - [Simultaneous determination of 23-antibiotics in mariculture water using solid
      phase extraction and high performance liquid chromatography-tandem mass
      spectrometry].
AB  - A method for the determination of 23 antibiotics from 6 categories in water was
      developed by using solid-phase extraction and high performance liquid
      chromatography-tandem mass spectrometry (SPE-HPLC-MS/MS). Water samples were
      enriched and cleaned-up by solid-phase extraction cartridges. The MS detection
      parameters of the analyzed antibiotics, the pH values of loading buffers and the
      volumes of the eluents were optimized by comparing the sample recoveries under
      different conditions. All antibiotics were separated by gradient elution with the
      mobile phases of 0.1% (v/v) formic acid and 1 g/L ammonium formate in water and
      aceto-nitrile-methanol (1:1, v/v) mixture. The eluate was then analyzed by HPLC
      MS/MS in both positive and negative electrospray ionization conditions with
      multiple reaction monitoring (MRM) mode. The method detection limits (MDLs) were
      in the range of 0.1-2.9 ng/L and the recoveries of 23 antibiotics in water ranged
      from 47.3% to 132.6%. The developed method was applied to the analysis of 5 water
      samples from mariculture ponds located in Dongying City, Shandong Province. The
      results showed that the antibiotics could be detected in all water samples. The
      trimethoprim showed the highest detection rate, and the florfenicol had the
      highest mass concentration which reached 261. 0 ng/L. The results showed that the
      developed method is efficient, sensitive and reliable, which is suitable for the
      detection of antibiotics in seawater samples.

PMID- 26292402
TI  - [Preparation of multi-walled carbon nanotubes decorated with Fe3O4 nanoparticles
      for determination of trace pyrethroid pesticides in water and honey samples].
AB  - A magnetic carbon nanotube hybrid material was prepared using a chemical co
      precipitation method. The Fe3O4 nanoparticles were enclosed onto the surface of
      the acid multi-walled carbon nanotubes (AMWNTs), and they were identified as
      Fe3O4/AMWNTs composites. This hybrid materials displayed typical
      superparamagnetic behavior, good dispersibility, and good adsorption capacity for
      pyrethroid pesticides. A magnetic solid-phase microextraction (MSPE) procedure
      based on Fe3O4/AMWNTs composites, combined with gas chromatography, was developed
      for the quantification of six pyrethroid pesticides in water and honey samples.
      Several important parameters affecting the extraction efficiency for six
      pyrethroid pesticides were optimized in sequential order, including ionic
      strength, extraction time and desorption time. Under the optimized conditions,
      this method showed wide linearity ranging from 0.5 ug/L to 50 ug/L with
      correlation coefficients (R2) higher than 0.990. The limits of detection (LODs)
      ranged from 0.07 ug/L to 0.20 ug/L at a singal-to-noise ratio of 3. The relative
      standard deviations (RSDs) ranged from 3. 8% to 8. 1%. Satisfactory recoveries (>
      78.4%) were obtained for the simultaneous analysis of the six pyrethroid
      pesticide residues in river water, fish-pond water and two honey samples. This
      method is sensitive and simple. It can meet the actual requirement for the
      analysis of trace analytes from environmental water and honey samples.

PMID- 26292404
TI  - [Multiresidue analysis of 63 veterinary drugs in meat by dispersive solid-phase
      extraction and high performance liquid chromatography-tandem mass spectrometry].
AB  - A novel multiresidue analytical method has been developed and validated for the
      determination of five classes of veterinary drugs including 18 beta-lactams, 15
      quinolones, 21 sulfonamides, 3 sulfonamide potentiators and 6 antiparasitics in
      meat using dispersive solid-phase extraction (dispersive-SPE) and high
      performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The
      analytes were extracted with a vortex mixer by 0.1 mol/L Na2 EDTA solution and
      acetonitrile containing 1% (v/v) acetic acid, and then the extracts were purified
      using dispersive-SPE with C18 sorbent. Electrospray ionization mass spectrometry
      was operated in positive mode using dynamic multiple reaction monitoring (DMRM)
      for the qualitative and quantitative analysis of the 63 analytes after the
      separation on a Poroshell EC-C18 column (100 mm x 2.1 mm, 2.4 um). The
      correlation coefficients of linear calibration curves were over 0.99 in the
      corresponding concentration ranges. The average recoveries of the 63 analytes
      ranged from 62.2% to 112.0%, and the relative standard deviations (RSDs) were
      3.1%-16.3% in spiked meat (pork, beef and chicken muscle) at three levels. The
      limits of detection (LODs, S/N >= 3) and the limits of quantification (LOQs, S/N
      >= 10) were 0.1-3.0 ug/kg and 0.5-10.0 ug/kg, respectively. The method is simple,
      rapid, sensitive, reliable and suitable for the determination of residues in
      animal products.

PMID- 26292405
TI  - [Determination of 22 acidic dyes in edible packagings by high performance liquid
      chromatography-tandem mass spectrometry].
AB  - A method for the simultaneous determination of 22 acidic dyes (acid yellow 23,
      acid red 18, acid blue 7, etc) in edible packagings was developed using high
      performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The
      samples were extracted with acetonitrile-methanol (5:5, v/v) , and then cleaned
      up with Strata-X-AW solid-phase extractor. The analytes were separated on a
      Zorbax Eclipse Plus C18 column (100 mm x 3.0 mm, 1.8 um) by gradient elution with
      acetonitrile-10 mmol/L ammonium acetate as the mobile phases. The 22 acidic dyes
      were determined by electrospray negative ion source (ESI-), and multiple reaction
      monitoring (MRM) mode. The qualitative analysis was based on the retention times
      and characteristic ion pairs consisting of one parent ion and two fragment ions,
      and the quantitative analysis was carried out by matrix-matched external standard
      method. The results showed that the calibration curves had good linearity for the
      22 acidic dyes, and the correlation coefficients (r2) were larger than 0. 991.
      The limits of quantitation (LOQs, S/N >= 10) were in the range of 0.1-2.0 mg/kg
      in three different matrices (plant capsule, gelatine capsule, oblatum). The
      average recoveries were in the range of 78.4%-109.5% for the 22 acidic dyes with
      the relative standard deviations (RSDs) from 4.6% to 14.5% at three spiked levels
      (1 x LOQ, 2 x LOQ and 10 x LOQ). This method is suitable for the determination of
      acidic dyes in edible packagings with the characteristics of high accuracy and
      precision.

PMID- 26292406
TI  - [Rapid screening and quantitative detection of 11 illegally added antidiabetics
      in health care products by ultra performance liquid chromatography
      quadrupole/electrostatic field orbitrap high resolution mass spectrometry].
AB  - A method for rapid screening and quantification of 11 antidiabetics (nateglinide,
      pioglitazone hydrochloride, gliquidone, gliclazide, glipizide, glibenclamide,
      metformin hydrochloride, repaglinide, phenformin hydrochloride, rosiglitazone
      hydrochloride, glimepiride) illegally added in health care products by ultra
      performance liquid chromatography (UPLC)-quadrupole/ electrostatic field orbitrap
      mass spectrometry was established. The samples were extracted with methanol, and
      separated on an Agilent Poroshell 120 SB-C18 column (100 mm x 4.6 mm, 2.7 um)
      with acetonitrile-10 mmol/L ammonium acetate solution as mobile phases by
      gradient elution. The positive mode was used in the MS detection. The resolution
      of the precursor mass was 70,000, while the resolution of the product mass was
      17,500. The results indicated that the linearity of all the 11 antidiabetics
      ranged from 0.005 mg/L to 0.5 mg/L with the correlation coefficients greater than
      0.99. The limits of detection were confirmed by spiked samples, and were between
      2.7 and 5.1 ug/kg for the 11 antidiabetics. The recoveries were in the range of
      87.3% to 98.3%, with the relative standard deviations in the range of 2.18%
      5.21%. This method is accurate, simple and rapid, and can be used in rapid
      screening and quantitative analysis of the 11 illegally added antidiabetics in
      health care products.

PMID- 26292407
TI  - [Determination of free carcinogenic aromatic amines in textiles by ultra
      performance liquid chromatography-linear ion trap/orbitrap high resolution mass
      spectrometry].
AB  - A method of ultra-performance liquid chromatography-linear ion trap/orbitrap high
      resolution mass spectrometry (UPLC-LTQ/Orbitrap MS) was used to determine 24 free
      carcinogenic aromatic amines in textiles. The main factors influencing the
      method, including the extraction solvent, the extraction temperature and the
      extraction time, were optimized. Under the optimized experimental conditions, the
      analytes were extracted by dichloromethane for 10 min and loaded into a ZORBAX SB
      C18 column (150 mm x 2.1 mm, 5 um) with a gradient elution of methanol and 0.1%
      aqueous formic acid solution, and finally detected by LTQ/Orbitrap MS. The
      screening and quantitative analysis were carried out by the accurate mass of
      quasi-molecular ion and the peak in extracted chromatogram with accurate mass
      respectively. The correlation coefficients (R2) were higher than 0.99. The
      recoveries were 87.8%-105.6% with the RSDs were 1.6%-3.4%. The limits of
      detection were 0.5-1 ug/kg, and the limits of quantification were 1.5-3 ug/kg.
      The proposed method was applied to 14 textile samples containing spandex. 4,4'
      Diaminodiphenylmethane was determined in five samples and the contents were 0.21
      25.6 mg/kg. The results indicate that the developed method is a simple,
      efficient, precise and reliable technique for the determination of free
      carcinogenic aromatic amines in textiles.

PMID- 26292408
TI  - [Exploration on serum metabolic biomarkers of hepatitis B virus infected patients
      based on gas chromatography-mass spectrometry].
AB  - Abstract: The difference of serum metabolome between hepatitis B virus (HBV)
      infected patients and healthy controls was explored for the potential metabolite
      biomarkers of HBV disease using serum metabolomics approach. Totally 30 HBV
      infected patients and 35 healthy controls were enrolled. Gas chromatography-time
      of-flight mass spectrometry (GC-TOFMS), pattern recognition by principal
      component analysis (PCA) and orthogonal partial least squares-discriminant
      analysis (OPLS-DA) were applied in each group. Several metabolites which were
      different between the two groups based on variable importance in projection (VIP)
      value, non-parametric test and screening in databases were identified. Ten
      variables that were significantly different were considered as the potential
      biomarkers, among which five variables (citric acid, aconitic acid, glutamine,
      N,N-dimethylglycine and malonic acid) showed good correlation with HBV patients.
      The area under the receiver operating characteristic curve was 0.975, with good
      specificity and sensitivity. A panel of metabolite markers composed of citric
      acid, aconitic acid, glutamine, N,N-dimethylglycine and malonic acid from GC
      TOFMS were selected to discriminate HBV subjects from their healthy counterparts.
      These biochemical changes provide a novel molecular diagnostic approach which
      could be helpful to further understand the pathogenesis and identify the
      therapeutic target of HBV disease.

PMID- 26292409
TI  - [Comparison of the performances of gas chromatography-quadrupole time of flight
      mass spectrometry and gas chromatography-tandem mass spectrometry in rapid
      screening and confirmation of 208 pesticide residues in fruits and vegetables].
AB  - The performances of gas chromatography-tandem mass spectrometry (GC-MS/MS) and
      gas chromatography quadrupole time of flight mass spectrometry (GC-QTOF/MS) for
      the determination of 208 pesticide residues in fruit and vegetable samples,
      including apple, orange, tomato and cucumber, were compared comprehensively.
      Based on the differences of the two instruments, their respective characteristics
      and scopes of application in the detection of the pesticide residues were
      presented, which provided the reference for the analysis of pesticide residues.
      The performance parameters of the two instruments, such as overall recoveries,
      precisions, limits of detection, linear ranges, identification points and matrix
      effects, were evaluated according to a designed experiment. At three spiked
      levels (5.0, 10.0 and 20.0 ug/kg), the average recoveries for the majority of
      pesticides (93.0%) ranged from 70% to 120% in the four matrices with relative
      standard deviations below 20%. The limits of detection for most of the pesticides
      by GC-MS/MS and GC-Q-TOF/MS were less than 5.0 ug/kg. Compared with GC-QTOF/MS,
      GC-MS/MS showed relatively lower limits of detection and wider linear ranges, and
      its performance was more satisfactory in accurate quantitative analysis due to
      its superior sensitivity. On the other hand, GC-QTOF/MS provided accurate mass
      measurement, which was proved to be an efficient analytical tool on the rapid
      screening and confirmation of a large number of pesticides and non-target
      compounds.

PMID- 26292410
TI  - [Fast analysis of common fatty acids in edible vegetable oils by ultra
      performance convergence chromatography-mass spectrometry].
AB  - A fast analytical method for five common fatty acids in six edible vegetable oils
      was developed by ultra-performance convergence chromatography-mass spectrometry
      (UPC2-MS). The five fatty acids are palmitic acid, stearic acid, oleic acid,
      linoleic acid and linolenic acid. Their contents in the corn oil, sunflower oil,
      soybean oil, tea oil, rapeseed oil and peanut oil were compared. The
      chromatographic separation was performed on an ACQUITY UPC2 BEH 2-EP column (100
      mm x 2.1 mm, 1.7 um) using the mobile phases of carbon dioxide and
      methanol/acetonitrile (1:1, v/v) with gradient elution. The separated compounds
      were detected by negative electrospray ionization ESF-MS. The results showed that
      the reasonable linearities were achieved for all the analytes over the range of
      0.5-100 mg/L with the correlation coefficients (R2) of 0.9985-0.9998. The limits
      of quantification (S/N >= 10) of the five fatty acids were 0.15-0.50 mg/L. The
      recoveries of the five fatty acids at three spiked levels were in the range of
      89.61%-108.50% with relative standard deviations of 0.69%-3.01%. The developed
      method showed high performance, good resolution and fast analysis for the
      underivatized fatty acids. It has been successfully used to detect the five fatty
      acids from corn oil, sunflower oil, soybean oil, tea oil rapeseed oil and peanut
      oil.

PMID- 26292411
TI  - [Electrokinetic chromatographic properties of amphiphilic copolymer poly (styrene
      co-methacrylic acid) self-assembled micelle pseudostationary phase].
AB  - The amphiphilic copolymer poly (styrene-co-methacrylic acid) (P (St-co-MAA)) with
      molar ratios of 6:4 and 7:3 self-assembled to form micelles. The polymeric
      micelles were used as pseudostationary phase (PSP) in micellar electrokinetic
      chromatography ( MEKC). Their physicochemical properties and MEKC performance
      were investigated as well in the present work. The critical micelle concentration
      ( CMC) , polarity, surface charge density and hydrodynamic diameter were used to
      characterize the solution physicochemical properties, while the methylene group
      selectivity was evaluated with n-alkylphenone homologous series. The time window
      and linear solvation energy relationship (LSER) analysis were used to
      characterize the MEKC retention behavior and the selectivity. All of these were
      compared with poly (methyl methacrylate-co-methacrylic acid) (P (MMA-co-MAA))
      with the molar ratio of 7:3 and sodium dodecyl sulfate (SDS) micellar systems.
      The results showed that P ( St-co-MAA) system had the minimum CMC, the widest
      time window and the best methylene group selectivity. LSER analysis results
      showed that the hydrophobic effect was the most important interaction between
      solutes and PSPs, and the hydrogen-bonding acidity was the second significant
      factor on selectivity and MEKC retention behavior. P (St-co-MAA) system,
      especially with the molar ratio of 7 :3, had the highest effective parameter in
      LSER and showed a high separation selectivity of PSP.

PMID- 26292412
TI  - [Determination of nine pesticide residues in vegetables by matrix solid-phase
      dispersion-ultra performance liquid chromatography-tandem mass spectrometry].
AB  - A matrix solid-phase dispersion-ultra performance liquid chromatography-tandem
      mass spectrometry (MSPD-UPLC-MS/MS) method was established for the simultaneous
      deter- mination of carbendiazin, omethoate, carbofuran, aldicarb, chlorpyrifos,
      methamidophos, phorate, parathion and parathion-methyl residues in vegetables.
      The samples were extracted by acetonitrile and separated with salting out method.
      And then the supernatants were purified by matrix solid-phase dispersion for the
      UPLC-MS/MS analysis. The separation was performed on a Waters Acquity UPLC system
      with a BEH C18 column with the gradient elution of acetonitrile and water
      containing 0. 1% (v/v) acetic acid. The nine pesticides were determined in the
      modes of electrospray positive ionization (ESI+) and multiple reaction monitoring
      (MRM). The ana- lytes were quantified by matrix matched standard solution curves.
      The limits of detection (S/N >= 3) were 0.8-4.0 ug/kg. The average recoveries
      were 72.8%-117.4%. The detection rates were 42.0% for chlorpyrifos, 14.0% for
      carbendiazin and 1.5% for dimethoate, and the exces- sive rate of chlorpyrifos
      was 8.0% in the determination of 50 real samples; the other pesticides were not
      detected. The method is simple, accurate and highly reproducible. This method is
      suit- able for the quality control of pesticide residues in risk monitoring of
      the safety of the foods.

PMID- 26292413
TI  - [Spectrum-effect relationship on anti-hepatic fibrosis effect of Radix Hedysari].
AB  - The spectrum-effect relationship on anti-hepatic fibrosis effect of Radix
      Hedysari was explored based on high performance liquid chromatographic technique.
      Hepatic fibrosis was induced in mice by administering a subcutaneous injection of
      carbon tetrachloride-peanut oil (4:6, v/v) continuously for 35 d at a interval of
      5 d (0.1 mL/10 g). And at the same time of modeling, the different extracts of
      Radix Hedysari were administered orally once daily at a dose of 10 g/kg. The
      ethanol extract of Radix Hedysari was specified to be most effective on anti
      hepatic fibrosis by determining the levels of alanine aminotransferase, aspartate
      transami- nase, total-protein, albumin, albumin/globulin (ALT, AST, TP, ALB, and
      A/G) in serum and relative liver weight. Subsequently, the grey relational degree
      analysis and partial least squares analysis were employed to reveal the
      correlation between chromatographic fingerprint of ethanol extract of Radix
      Hedysari from 10 different geographical origins and its anti-hepatic fibrosis
      efficacy. The results suggest that most chemical constituents of Radix Hedysari
      have a high correlation with the effect of anti-hepatic fibrosis (> 0.8), which
      indicates that the effect is related to the various components in Radix Hedysari.
      Adenosine, calycosin and ononin in ethanol extract of Radix Hedysari have been
      identified separately among which adenosine and calycosin made the great
      contribution to the anti-hepatic fibrosis effect.

PMID- 26292414
TI  - [Determination of ethylene glycol bis (2-aminoethyl) ether-N,N,N,N-tetraacetic
      acid in medicine using high performance liquid chromatography].
AB  - A method was developed for the determination of ethylene glycol bis(2-aminoethyl)
      ether-N,N,N,N-tetraacetic acid (EGTA) by high performance liquid chromatography
      (HPLC). The content of EGTA can be determined by that of EGTA-Cu through the
      complexation between EGTA and Cu2+. The chromatographic separation was performed
      on an Ultimate-AQ C18 analytical column (250 mm x 4.6 mm, 5 um) using the mobile
      phase of acetonitrile-ion-pairing reagents (with 0.3% tetrabutyl ammonium
      hydroxide in mass fraction adjusted to pH 6.50 using acetate)-buffered saline (35
      mmol/L sodium acetate of pH 6.50) (20:20:60, v/v/v). The chromatographic
      conditions were as follows: flow rate, 1.50 mL/min; detection wavelength, 245 nm;
      injection volume, 100 uL; column temperature, 40  degrees C. Under the
      conditions, good linear relationships between the mass concentration and the peak
      area of EGTA were observed in the range of 0.10-15.00 mg/L (R = 0.9998). The
      limit of detection (LOD, S/N = 3) and limit of quantitation (LOQ, S/N = 10) were
      determined as 0.05 mg/L and 0.17 mg/L, respectively. The average recoveries were
      98.34%-99.03% with the RSDs of 1.08%-3.33% (n = 9). The results showed that the
      developed method is sensitive, accurate, reproducible and suitable for the
      analysis of EGTA in medicine.

PMID- 26292415
TI  - [Simultaneous determination of 11 constituents in Citrus reticulate 'Chachi' by
      high performance liquid chromatography].
AB  - An HPLC method was developed for the simultaneous determination of 11
      constituents, 5-hydroxymethyl furfural (5-HMF), vicenin-2, hesperidin,
      hesperetin, isosinensetin, sinensetin, tetramethyl-O-isoscutellarein (TEOS),
      nobiletin, 3, 5, 6, 7, 8, 3', 4'-heptamethoxy- flavone (HEPTA), tangeretin, 5
      demethylnobiletin in Citrus reticulate 'Chachi'. The separation was conducted on
      a Hanbon Benatach C18 column (250 mm x 4.6 mm, 5 um) with acetonitrile and 0.2%
      formic acid as mobile phases with gradient elution. The flow rate was 1.0 mL/min.
      The detection wavelength was 280 nm. The column temperature was 25  degrees C.
      The results showed that the correlation coefficients (r) between concentration
      and chromatographic peak area of the 11 constituents were over 0.998 in the
      selected linear ranges. The limits of detection (LODs, S/N = 3) and limits of
      quantification (LOQs, S/N = 10) of the 11 constituents were in the range of
      0.0125-1.25 mg/L and 0.0502-4.99 mg/L, respectively. The average recoveries (n =
      3) of the 11 constituents were in the range of 96.4%-102.4% and the RSDs were
      0.25%-4.01%. The developed method has been successfully applied for the analysis
      of eight samples from different cultivation regions in Guangdong Province. This
      method is simple, accurate and effective for the simultaneous determination of
      the 11 components, and suitable for the quality control of Citrus reticulate
      'Chachi'.

PMID- 26292416
TI  - [Separations of four groups of analogues on cyclofructan based columns].
AB  - The separations of the immunosuppressive reagents, capsaicinoids, vitamin E,
      curcumins on cyclofructan based stationary phases containing polystyrene
      supported native cyclofructan (MCI Gel CRS100), silica supported native
      cyclofructan (Frulic N), silica supported isopropyl carbamate cyclofructan 6
      (Larihc P), silica supported R-naphthylethyl carbamate cyclofructan 6 (Larihc RN)
      in normal phase HPLC mode were studied. From the investigation it showed that the
      column MCI Gel CRS100 was more suitable for the separation in normal phase than
      in hydrophilic interaction liquid chromatography. Derivatized cyclofructan
      stationary phases, Larihc P and Larihc RN, showed better selectivities in
      comparison with the native cyclofructan stationary phases. Trifluoroacetic acid
      had less influence on resolution on cyclofructan based stationary phases in
      normal phase mode.

PMID- 26292417
TI  - [Determination of 11 sulfonamide residues in aquaculture water and sediments by
      high performance liquid chromatography coupled with post-column derivatization].
AB  - An analytical method was developed for the determination of 11 sulfonamide
      compounds in aquaculture water and sediments by high performance liquid
      chromatography (HPLC) coupled with post-column derivatization. The filtered water
      sample was purified and concentrated with HLB cartridge, while the sediment
      sample was extracted with a mixture of methanol and EDTA-McIlvaine buffer (1:1,
      v/v), and then purified and enriched through HLB solid-phase extraction. The
      sulfonamides were separated on a C18 column by HPLC and on-line derivatized with
      a fluorescamine and detected with a fluorescence detector. The parameters of post
      column derivatization system were optimized, and the fluorescamine solution
      concentration, velocity of reagent solution and reaction temperature were 0.2
      g/L, 0.15 mL/min and 50  degrees C, respectively. The calibration curves of the
      method showed good linearity in the range of 0.01-1.0 mg/L, with the correlation
      coefficients (r2) all above 0.99995. The recoveries were 79.3%-100.7% and 74.6%
      95.3% with RSD values of 2.2%-11.0% and 2.6%-10.3% for the 11 sulfonamides in
      aquaculture water and sediments, respectively. The respective limits of detection
      (LODs, S/N = 3) were 0.9-5.5 ng/L and 0.3-1.3 ug/kg and the limits of
      quantification (LOQs, S/N = 10) were 3.0-18.1 ng/L and 1.0-4.4 ug/kg. The method
      can be applied to the determination of sulfonamides in the aquaculture
      environment, and it has a good practicability.

PMID- 26292418
TI  - [Analysis of 1,4-dioxane in drinking water by headspace solid-phase
      microextraction-gas chromatography].
AB  - A method for the detection of trace 1,4-dioxane in drinking water using headspace
      solid-phase microextraction (HS/SPME ) with gas chromatography/flame ionization
      detector (FID) was presented. Both the extraction conditions (SPME fiber,
      extraction temperature, extraction time, pH and sample volume, et al) and the gas
      chromatographic conditions were optimized. The results showed that the best
      response was obtained with 85 um Carboxen-PDMS above 3 mL water in a 20-mL screw
      capped vial containing 3 mL sodium hydroxide solution (600 g/L). The best
      chromatographic separation was obtained on a PTA-5 capillary column (30 m x 0.53
      mm x 3.0 um) which was modified with alkali-bonding and of large pores and thick
      film. The linear range for 1,4-dioxane was 0.50-50.0 ug/L with the correlation
      coefficient (r) of 0.9995. The limit of detection (S/N > 3) was 0.14 ug/L. The
      recoveries for the actual water samples at low, medium and high spiked levels
      were 95.5%-107%, with the relative standard deviations of 1.1%-5.3% (n = 6). The
      developed method is simple, accurate, reproducible and highly sensitive. It is
      suitable for the routine monitoring of trace amount of 1,4-dioxane in the
      drinking water.

PMID- 26292419
TI  - [ESTIMATION OF IONIZING RADIATION EFFECTIVE DOSES IN THE INTERNATIONAL SPACE
      STATION CREWS BY THE METHOD OF CALCULATION MODELING].
AB  - Monitoring of the radiation loading on cosmonauts requires calculation of
      absorbed dose dynamics with regard to the stay of cosmonauts in specific
      compartments of the space vehicle that differ in shielding properties and lack
      means of radiation measurement. The paper discusses different aspects of
      calculation modeling of radiation effects on human body organs and tissues and
      reviews the effective dose estimates for cosmonauts working in one or another
      compartment over the previous period of the International space station
      operation. It was demonstrated that doses measured by a real or personal
      dosimeters can be used to calculate effective dose values. Correct estimation of
      accumulated effective dose can be ensured by consideration for time course of the
      space radiation quality factor.

PMID- 26292420
TI  - [IMMEDIATE RADIOBIOLOGICAL EFFECTS IN MICE FOLLOWING gamma-IRRADIATION BY LOW
      DOSES].
AB  - Outbred CD-1 mice females aged 4 to 4.5-months were investigated in 21-22 hours
      following total gamma-irradiation at 10, 25, 50, 75, 100 and 200 mGy. Loss in
      bone marrow karyocytes, as well as spleen and thymus mass reductions were
      significant in the group of animals irradiated at 50 and 200 mGy and less
      dramatic in mice irradiated at 75 mGy. The orientative-trying behavior reaction
      (OTBR) in the open field tested in 19-20 hours after exposure to 10 and 25 mGy
      was reliably stronger than in the group of biological control; however, emotional
      status (ES) in the animals that received 10 mGy dropped significantly. Mice
      irradiated at 50 mGy were found to weaken the grip of their front limbs. Dose
      levels differing in opposite radiobiological effects on the parameters under
      study were established. Doses in the range from 10 to 25 mGy maximized OTBR and
      ES, while doses of 50, 100 and 200 mGy produced high reactions of the immune and
      hemopoietic organs.

PMID- 26292421
TI  - [COMPREHENSIVE ASSESSMENT OF THE HEMOSTASIS SYSTEM IN TEST-SUBJECTS IN EXPERIMENT
      "MARS-500"].
AB  - The paper is devoted to the hemostasis studies in the course of long-term (520 d)
      isolation in an airtight chamber. Measured parameters included activated partial
      thromboplastin time (APTT), international normalized ratio (INR), thrombin time
      (TT); concentrations of fibrinogen (FBG), plasminogen (PG), Willebrand factor
      (WF), tissue factor pathway inhibitor (TFPI), and tissue plasminogen activator
      (TPA), thrombomodulin (TM); activities of the coagulation cascade factors (II, V,
      VII, X, VIII, IX, XI, XII), antithrombin III (ATIII), protein C (PC), C1
      inhibitor (C1), alpha2-antiplasmin (AP), TPA and TFPI. The investigation revealed
      a diversity of changes in the plasma fibrinogen concentration, slower blood
      coagulation in the intrinsic pathway and the final stage, and a relative rise in
      the activities of ATIII and PC-inhibited factors. The rest parameters showed
      different trends.

PMID- 26292422
TI  - [FREQUENCY-TEMPORAL STRUCTURE OF HUMAN ELECTROENCEPHALOGRAM IN THE CONDITION OF
      ARTIFICIAL HYPOGRAVITY: DRY IMMERSION MODEL].
AB  - Frequency-temporal electroencephalogram (EEG) reactions to hypogravity were
      studied in 7 male subjects at the age of 20 to 27 years. The experiment was
      conducted using dry immersion (DI) as the best known method of simulating the
      space microgravity effects on the Earth. This hypogravity model reproduces
      hypokinesia, i.e. the weight-bearing and mechanic load removal, which is typical
      of microgravity. EEG was recorded by Neuroscan-2 (Compumedics) before the
      experiment (baseline data) and at the end of day 2 in DI. Comparative analysis of
      the EEG frequency-temporal structure was performed with the use of 2 techniques:
      Fourier transform and modified wavelet analysis. The Fourier transform elicited
      that after 2 days in DI the main shifts occurring to the EEG spectral composition
      are a decline in the alpha power and a slight though reliable growth of theta
      power. Similar frequency shifts were detected in the same records analyzed using
      the wavelet transform. According to wavelet analysis, during DI shifts in EEG
      frequency spectrum are accompanied by frequency desorganization of the EEG
      dominant rhythm and gross impairment of total stability of the electrical
      activity with time. Wavelet transform provides an opportunity to quantify changes
      in the frequency-temporal structure of the electrical activity of the brain.
      Quantitative evidence of frequency desorganization and temporal instability of
      EEG wavelet spectrograms may be the key to the understanding of mechanisms that
      drive functional disorders in the brain cortex in the conditions of hypogravity.

PMID- 26292423
TI  - [HEART RHYTHM VARIABILITY ANALYSIS AND ASSESSMENT OF THE SPINAL PAIN SYNDROME
      DURING DRY IMMERSION].
AB  - The spinal pain syndrome appears in cosmonauts on both short and long-duration
      missions. This untoward factor may affect body systems functioning and complicate
      the successful accomplishment of space mission. Purpose of the investigation was
      to examine the lumbar spine and to elucidate whether its condition relates to the
      spinal pain development and changes in heart rate variability (HRV) in the
      microgravity environment. The experiment was conducted in dry immersion as a
      method of microgravity effects simulation. It was shown that in dry immersion
      locomotion reproduces the patterns peculiar for significant gravitational
      unloading. Spinal pain intensity, angles and heights of the lumbar intervertebral
      discs and HRV were measured in 19 selected volunteers. During the experiment, all
      the volunteers developed pains in the back that abated gradually. Pain dependence
      on the height of intervertebral discs and cardiac regulatory mechanisms were
      investigated.

PMID- 26292424
TI  - [EXPERIMENTAL AND THEORETICAL STUDIES OF HUMAN HYPERCAPNIC VENTILATORY RESPONSE
      WITH THE USE OF MATHEMATICAL GAS EXCHANGE MODELING].
AB  - A mathematical model of biotechnical system integrating the human
      cardiorespiratory system with hard- and software was designed to investigate
      breathing control. The model describes dynamics of carbon dioxide and oxygen in 3
      biotechnical system compartments in the course of rebreathing tests. The tests do
      not require tanks with compressed gas and, therefore, can be performed in space
      flights. Results of simulated modeling of the ventilation response in 2 breath
      tests, i.e. to hypercapnia due to rebreathing of a hyperoxic gas mixture and to
      hypercapnia combined with hypoxia due to air rebreathing, are presented. Model
      validity was verified by comparison of the modeling and experimental data. The
      mathematical model made it evident that CO2 partial pressures in tissues, lungs
      and the breathing circuit equalize very fast when initial carbon dioxide
      concentration in the respiration circuit is equal to the end-tidal CO2
      concentrations in man at rest.

PMID- 26292425
TI  - [CYSTEAMINE-INDUCED MODIFICATION OF CYTOGENETIC DAMAGES TO THE CORNEAL EPITHELIUM
      OF MICE EXPOSED TO CORPUSCULAR RADIATION WITH VARYING LINEAR TRANSFER ENERGIES].
AB  - Cytogenetic damages to cells of the corneal epithelium were studied in mice
      exposed to protons (10, 25, 50 and 645 MeV), ions of boron, carbon and neon, and
      X-rays (180 keV) within the dose range from 25 to 750 cGy and injected with a
      radioprotector. Animals were subjected to a single exposure. The protective
      effect of beta-mercaptoethylamine was tested in the experiment. The
      radioprotector (0.2 ml) was introduced intraperitoneally 30 minutes before
      exposure in 350 mI/kg dose. Control animals received the same amount of sodium
      chloride solution. The animals were sacrificed by cervical dislocation in 24 and
      72 hrs. after exposure. It was shown that cysteamine effectively protects in vivo
      corneal epithelium cells of mice exposed to electromagnetic radiation or protons
      in a broad energy spectrum (10 to 645 MeV), and to a broad range of radiation
      doses (25 to 750 cGy), as judged from levels of aberrant mitosis and mitotic
      activity. The radioprotector exhibited the highest effectiveness in animals
      exposed to the doses of 50 to 300 cGy. These findings prove that cysteamine may
      potentially be used for pharmacological protection from protons. The
      radioprotector failed to prevent chromosomal aberrations after exposure to heavy
      charged particles of boron, carbon and neon, which implies the need to design
      radioprotectors against this type of corpuscular radiation specifically.

PMID- 26292426
TI  - [MORPHOLOGICAL ASPECTS OF CHANGES IN THE SPINAL GRAY MATTER DUE TO G-LOADS IN
      EXPERIMENT].
AB  - To study changes in spinal cord structures brought about by g-loads, laboratory
      animals (rats) were rotated on a centrifuge following a special procedure.
      Systematic g-loads along the craniocaudal axis resulted in reactive alterations,
      and also obvious destructive processes in the spinal gray matter (SGM). Light
      optical microscopy discovered that part of neurons had bodies with less intensive
      dying. Electron microscopy showed that among the cytoplasmic structures
      mitochondria were particularly sensitive to g-loads, which could affect
      mitochondrial oxidation. In the lumbar, these changes were observed in every
      segment under study; they were more significant in comparison with those found in
      cervical and thoracic segments of the spinal cord. Interneuron disintegration at
      neural centers revealed itself by the "light" type degeneration of synapses.
      Changes in capillaries included nuclei deformations and destruction of organelles
      in endotheliocytes, pericapillary edema, and erythrocytes sludge in the lumen.
      Inequality of spinal cord changes suggests the mosaic pattern of their
      distribution. Furthermore, their manifestation grew with the cranicaudal gradient
      so that the most conspicuous destructive developments occurred in the lumbar but
      not in the thoracic let alone the cervical segment. Acute g-loads gave rise to
      reactive changes in neurons and interneuron synapses that were the morphological
      markers of increased functional activity of neurons and activation of interneuron
      firing. In addition to the reactive changes, chronic g-loading also produced
      destructive disorders in GSM structures. These changes were not observed
      following acute g-loads and, therefore, resulted from multiple g-exposures and
      were cumulative.

PMID- 26292428
TI  - [THE 6TH INTERNATIONAL CONGRESS "MEDICINE IN SPACE AND EXTREME ENVIRONMENTS"].

PMID- 26292427
TI  - [INVESTIGATION OF IRON, ZINC, STABLE STRONTIUM AND LITHIUM CONTENT IN BIOLOGICAL
      FLUIDS AND TISSUES DURING EXPERIMENTAL SPACE FLIGHT SIMULATION].
AB  - In an experiment with space flight simulation, atomic emission spectral analysis
      with inductively coupled argon plasma was employed to measure iron, zinc, stable
      strontium and lithium in blood serum and its ultrafiltered fraction, and
      excretion with daily urine and hair. Monitoring of serum iron and its ultraviolet
      fraction showed good balance of these parameters in all periods of the
      experiment. Blood serum was found to contain exclusively iron bound with protein
      carriers. In the experiment, serum zinc was distinctively dependent on the
      nutrient status. Stable strontium excretion with daily urine can be a biological
      indicator of its homeostasis. The experiment factors had no effect on the lithium
      form in serum, i.e. lithium was invariably present in the ionized form and in
      quantities equal to ultrafiltered lithium in all blood samples in all periods of
      the experiment.

PMID- 26292429
TI  - ORNAC Strategic Planning: 2015-2018.

PMID- 26292430
TI  - EVALUATING THE USE OF CEILING LIFTS IN THE OPERATING ROOM.
AB  - Healthcare workers make up 11% of British Columbia's workforce and, on an annual
      basis, they account for over 7,500 time-loss claims, 300,000 days of work lost,
      and a cost of more than $50 million in health claims as a result of musculo
      skeletal injuries (MSIs) that occur in the workplace relating to patient care,
      over-exertion, slips, trips and violence. A new acute care hospital was
      constructed in Abbotsford, BC and opened in 2008. During this construction,
      extensive ceiling lift coverage was provided throughout the facility including in
      the operating room (OR). Given a lack of literature and research, around this
      important ergonomic engineering control in the OR environment, a staff survey was
      administered to capture information on the familiarity, usage, and perception of
      the ceiling lifts. Findings were positive and showed that the staff felt ceiling
      lifts were a practical and useful ergonomic engineering control, for the OR
      environment, and that key patient handling tasks were now being carried out with
      the use of ceiling lifts.

PMID- 26292431
TI  - A REFLECTIVE STUDY ON ABORTIONS IN THEATRE.
AB  - This article discusses the concept of conscientious objection in relation to
      surgical terminations of pregnancy. It explores a scrub nurse's duty of care not
      only to the patient but to themselves. It highlights the importance of being self
      aware of one's moral and emotional attitude towards abortions in theatre. Doing
      so enables the nurse/ODP to practice professionally and autonomously, and to
      deliver the highest level of perioperative care whilst respecting their personal
      rights.

PMID- 26292432
TI  - SPOTLIGHT ON ORNAC MEMBERS. AN INTERVIEW WITH ESTHER ENG RN, BN, CPN(C) & ANNE
      CHANG RN, BN, CPN(C) WINNERS OF THE ORNAC PERIOPERATIVE NURSES WEEK CAMPAIGN
      CONTEST.

PMID- 26292434
TI  - Getting Your Name in Lights (almost).

PMID- 26292433
TI  - Changing of the Guard.

PMID- 26292435
TI  - Delirium: The Nurse's Role in Prevention, Diagnosis, and Treatment.
AB  - Delirium is an acute change in mental status typically caused by a medical
      condition. Delirium complicates care, increases safety risks, and has a negative
      impact on patient outcome. By identifying mental status changes early, the nurse
      is in a strategic position to prevent delirium in 30%-40% of at-risk patients. An
      interdisciplinary team approach can prevent, diagnose, and treat delirium to
      improve safety, reduce cost of care, and optimize patient outcomes.

PMID- 26292436
TI  - Symptom-Triggered vs. Fixed-Dosing Management of Alcohol Withdrawal Syndrome.
AB  - A literature review was conducted with the objective of creating evidence-based
      recommendations for use of symptom-triggered therapy (STT) or fixed-schedule
      dosing in treating alcohol withdrawal syndrome in inpatients. Use of STT reduced
      duration of therapy as well as the number of patients requiring treatment or
      medication, potentially reducing costs and risk of adverse medication reactions.

PMID- 26292437
TI  - Women with Type 2 Diabetes and Glycemic Control.
AB  - Mid-life women are vulnerable to the complications associated with diabetes. This
      research examined factors predicting glycemic control. Diabetes knowledge was
      found to be high in the group. Daily self-measurement of blood glucose predicted
      better glycemic control.

PMID- 26292438
TI  - Nurses' Knowledge of Heart Failure: Implications for Decreasing 30-Day Re
      Admission Rates.
AB  - Heart failure affects 5.1 million Americans. It is the leading cause of
      hospitalization in older adults and the most common cause of readmissions, which
      cost approximately $12 billion annually. Readmissions can be reduced through
      increased nurses' knowledge in heart failure.

PMID- 26292439
TI  - Reducing Medication Errors By Educating Nurses on Bar Code Technology.

PMID- 26292440
TI  - Lesson Learned: Don't be Cynical or Grumpy.

PMID- 26292441
TI  - Interactive Learning and Networking At Successful AMSN Convention.

PMID- 26292442
TI  - IV Therapies for Patients with Fluid and Electrolyte Imbalances.

PMID- 26292443
TI  - Collaborative Learning: Student Nurses Caring for Community Residents.

PMID- 26292444
TI  - Emerging Roles for Nurses After Health Care Reform.

PMID- 26292445
TI  - Venous Thromboembolic (VTE) Prophylaxis: Part I.

PMID- 26292446
TI  - VTE Prevention: Development of an Institutional Protocol and the Nurse's Role.
AB  - Venous thromboembolism (VTE), including the combined diseases of deep vein
      thrombosis and pulmonary embolism, is a significant health problem that affects
      mortality, morbidity, and resource expenditure. Multiple guidelines have been
      formulated to address this condition, but broad implementation in health care is
      lacking. Nurses have a pivotal role in VTE prevention through increased
      knowledge, patient advocacy, and implementation/development of institutional VTE
      protocols.

PMID- 26292447
TI  - Impact of SBAR on Nurse Shift Reports and Staff Rounding.
AB  - The Situation-Background-Assessment-Recommendation (SBAR) protocol was used to
      improve shift reports and interdisciplinary rounding. On a medical-surgical unit,
      observations were conducted before and after implementation. Both processes were
      significantly shorter and more consistent. SBAR enabled more focused and
      efficient communication.

PMID- 26292448
TI  - A Power in Clinical Nursing Practice: Concept Analysis on Nursing Intuition.
AB  - Growing evidence suggests intuition in nursing is an important part of effective
      clinical decision making that supports safe patient care. In this article, the
      concept of intuition as it relates to decision-making processes among novice
      nurses is analyzed.

PMID- 26292449
TI  - Attitudes of Nurses Toward Pressure Ulcer Prevention: A Literature Review.
AB  - Despite the existence of accepted guidelines to prevent pressure ulcers,
      interventions are not performed consistently. Many variables, including nurses'
      attitudes, contribute to the development of pressure ulcers. A review of the
      literature on nurses' attitudes toward pressure ulcer prevention is provided.

PMID- 26292450
TI  - We Can Do Better.

PMID- 26292451
TI  - You Bet: There's an App for That!

PMID- 26292452
TI  - Indoor Tanning Legislation: Shaping Policy and Nursing Practice.
AB  - Legislation exists regulating adolescents' use of tanning beds; however, the rate
      at which adolescents use these devices has not been reduced. The purpose of this
      study was to provide an analysis of indoor tanning bed legislation in the United
      States specifically related to legal issues and parental consent along with
      enforcement of current laws. The investigators collected data via review of state
      health department websites or telephone interviews of identified contacts for all
      50 states. Findings reveal wide variation in legislation related to adolescents'
      access to tanning devices and enforcement of violation of legal statutes. Nurses
      and other health care professionals can play key roles in educating families and
      adolescents to the dangers from the use of tanning beds along with being role
      models for proper skin protective behaviors. In addition, nurses should become
      advocates by supporting legislative efforts that ban tanning salons for all
      minors, with the long-term goal of reducing skin cancer caused by ultraviolet
      radiation (UVR) exposure from the use of tanning salons today.

PMID- 26292453
TI  - The Role and Impact of Animals with Pediatric Patients.
AB  - Animal-facilitated therapy (AFT), more specifically known as animal-assisted
      therapy (AAT) or "pet therapy," has had an increased presence in the literature
      with a surge of recent research methodologies exploring this complementary
      alternative medicine (CAM) intervention. However, limited studies have been
      conducted in the pediatric population, with many articles anecdotal in nature. A
      literature review included primary data sources PubMed, PsychINFO, Medline, and
      CINAHL, and yielded positive and beneficial outcomes to be gained through AAT in
      the pediatric population. Primary outcome variables of decreased anxiety and pain
      are the most commonly reported results. Further research studies are indicated to
      include the effects of AFT with children with different diseases and diagnoses.
      Exploration of other psychosocial and physical variables, such as self-esteem,
      would be useful. Interdisciplinary strategies are needed to develop interventions
      to help reduce patient symptoms and treatment-associated stress, as well as to
      facilitate healing and wellness beyond traditional medical treatment plans.
      Complementary therapies are of continued interest to the health care community,
      especially for pediatric nurses. Effective use of animals to facilitate
      conversation, lead discussion, or break communication barriers has been
      demonstrated through both research and anecdotal reports.

PMID- 26292454
TI  - Evolution of Growth Hormone Devices: Matching Devices with Patients.
AB  - Self-injection of growth hormone (GH) by children with GH deficiency can be
      problematic. They may have difficulty manipulating injection devices or preparing
      medication, and injections can be painful and create anxiety. Adherence to daily
      GH injections optimizes treatment benefit. Studies indicate that injection pens
      or needle-free devices enable easy self-injection by children, minimize
      medication reconstitution and storage requirements, and reduce injection pain.
      Newer GH delivery devices potentially encourage improved patient adherence.
      Reviewing features of GH devices will help nurses decide which GH device best
      fits the needs and abilities of pediatric patients. We searched recent medical
      literature about GH device development, about device-associated patient
      preferences and treatment adherence, and comparisons among GH devices. We
      concluded that improved awareness of the strengths and limitations of GH devices
      will enable nurses to guide families in selecting and using GH devices, improving
      adherence and outcomes, and helping children reach full growth potential.

PMID- 26292455
TI  - Adolescent Psychological Birth Trauma Following Cesarean Birth.
AB  - This study explored associations between depressive symptoms, violence exposure,
      and psychological birth trauma (PBT) among 44 adolescents experiencing cesarean
      births. Within 72 hours postpartum, symptoms of PBT were measured via a
      subjective rating of the birth experience and the Impact of Event Scale (IES).
      The Edinburgh Postnatal Depression Scale measured depressive symptoms. Single
      questions assessed violence exposure, including child abuse, partner violence,
      and traumatic life experiences as attribute variables. Adolescents were typically
      single with an unplanned first pregnancy. A similar number of adolescents
      reported a negative or positive birth experience. Correlations between IES
      scores, parity, depressive symptoms, partner violence, gestational age, and a
      negative birth appraisal suggested interconnected prenatal vulnerabilities for
      birth trauma and adverse infant outcomes. Partner violence and depressive
      symptoms need continuous assessment throughout pregnancy. The potential for
      continued symptoms and presence of violence beyond discharge requires follow up
      and education in pediatric settings at well-baby and routine visits.

PMID- 26292456
TI  - Building Theory.

PMID- 26292457
TI  - Transitions from Pediatric to Adult Care: Programs and Resources.
AB  - This third article in a series on the critical issue of the transition from
      pediatric to adult care for young adults with complex chronic conditions offers
      resources, including information about exemplary programs, to pediatric nurses.
      Three hospital-based programs are highlighted, four key Internet resources are
      identified, and five relevant articles are annotated. This information can
      support pediatric nurses in considering transition support options for individual
      teens and their families as well as in developing resources and designing
      programs in their own settings.

PMID- 26292458
TI  - Autoimune Conditions Associated With Type 1 Diabetes.
AB  - Type 1 diabetes is the most commonly seen endocrinopathy in pediatrics. This is
      an autoimmune condition. Children with type 1 diabetes are at much greater risk
      for other autoimmune conditions, particularly autoimmune thyroiditis, most
      commonly Hashimoto's thyroiditis, and celiac disease. It is important for the
      primary care practitioner to be aware of subtle symptoms of these conditions and
      how to screen for them because early treatment of both conditions can lead to
      better diabetes control and improved health in general.

PMID- 26292460
TI  - Too close to call?

PMID- 26292461
TI  - The heart of infection prevention.

PMID- 26292462
TI  - Process management.
AB  - Continuously meeting, and exceeding, the needs of our customers is one of the
      core requirements for any successful organization. This is no different for
      hospital trusts when providing secondary health services within the UK, they are
      continually in the spotlight to save costs and are bring urged to take on the
      role of 'small businesses' and have an independent view of their business and
      their stakeholders.

PMID- 26292463
TI  - Diversities in perceived knowledge and practice of preoperative skin preparation
      in Swedish orthopaedic surgery.
AB  - Preoperative skin preparations may reduce the risk of hospital-acquired
      infections. This cross sectional questionnaire study aimed to identify the
      practice and knowledge of preoperative skin preparation in Swedish orthopaedic
      surgery departments. One hundred and six respondents (response rate 68%) from 13
      Swedish orthopaedic departments reported a diversity of current recommendations
      and evidence, and good knowledge of skin preparations. This study found
      variations in practice and deviations from recommendations, despite high levels
      of knowledge.

PMID- 26292464
TI  - Improving operation notes and postoperative care: an audit of current practice.
AB  - The operation note is the single most important document in surgical practice.
      Ninety one operation notes were assessed on their adherence to guidelines, as
      well as their legibility and ability to inform postoperative care; as judged by
      five different healthcare professionals. Results showed a deficiency in essential
      information and poor legibility overall. Re-audit of 103 operation notes after
      intervention showed an improvement in nearly all criteria measured. The results
      indicate that education about current guidelines and an increase in word
      processing of operation notes improves quality of documentation, and therefore of
      postoperative care.

PMID- 26292465
TI  - Lifting incise drapes off the skin during wound closure can cause contamination.
AB  - Incise drapes adhere well to skin and reduce bacterial migration into the wound.
      We took skin swabs before and after the application of incise drapes during 49
      hip and knee arthroplasty procedures. Contamination was detected under incise
      drapes in four cases (8.1%) and consisted mainly of skin flora. We conclude that
      it is important to clean the skin again with antiseptics if the incise drape is
      removed by the surgeon.

PMID- 26292466
TI  - The first royal appendix abscess drainage.
AB  - On January 22nd 1901, at Osborne House on the Isle of Wight, Queen Victoria,
      nearing her 82nd birthday and having ruled for 64 years, drew her last breath.
      Edward Prince of Wales, 59 years of age, was now King Edward VII. A year of
      mourning was proclaimed and his coronation scheduled for June 26th. It was
      unexpectedly delayed by an attack of royal appendicitis. On Saturday June 14th
      1902, less than two weeks before the coronation, Edward travelled to Aldershot to
      attend a military review. It was a cold, rainy day and the King did not feel
      well. That night, his abdominal discomfort was getting worse and by five next
      morning the King's personal physician, Sir Francis Laking, was called to see him.
      Laking asked Sir Thomas Barlow, Physician-Extraordinary to the King, for a second
      opinion. By now there was fever, rigor and distinct tenderness in the right iliac
      fossa of the very obese abdomen. Under heavy sedation, the King was transferred
      to Windsor Castle, leaving his Queen, Alexandra, to review the parade of 30,000
      soldiers gathered at Aldershot.

PMID- 26292467
TI  - Introduction: The Food and Drug Law Institute Perspective.

PMID- 26292468
TI  - Introduction: The Georgetown Law Perspective.

PMID- 26292469
TI  - The Varieties and Limits of Transparency in U.S. Food Law.

PMID- 26292470
TI  - COOL Story: Country of Origin Labeling and the First Amendment.

PMID- 26292471
TI  - The End of "Patent Medicines"? Thoughts on the Rise of Regulatory Exclusivities.

PMID- 26292472
TI  - Effectively Regulating E-Cigarettes and Their Advertising--And the First
      Amendment.

PMID- 26292473
TI  - 2nd Annual Eric M. Blumberg Memorial Lecture.

PMID- 26292474
TI  - FDA-EPA Public Health Guidance on Fish Consumption: A Case Study on Informal
      Interagency Cooperation in "Shared Regulatory Space".
AB  - This article is a case study on how administrative agencies interact with each
      other in cases of shared regulatory jurisdiction. The theoretical literature on
      the topic of overlapping jurisdiction both (1) makes predictions about how
      agencies are expected to behave when they share jurisdiction, and (2) in recent
      iterations argues that overlapping jurisdiction can confer unique policymaking
      benefits. Through the lens of that theoretical literature, this article examines
      the relations between the Food and Drug Administration (FDA) and the
      Environmental Protection Agency (EPA) regarding the public health risks posed by
      mercury in fish. It concludes that the FDA-EPA case study (1) corroborates the
      extant theoretical accounts of how agencies behave in cases of overlapping
      jurisdiction, (2) supports the conclusion of the recent scholarship that
      overlapping jurisdiction can confer unique policy benefits, and (3) reveals a few
      wrinkles not given adequate treatment in the extant literature.

PMID- 26292475
TI  - Embracing 21st Century Information Sharing: Defining a New Paradigm for the Food
      and Drug Administration's Regulation of Biopharmaceutical Company Communications
      with Healthcare Professionals.
AB  - The Food and Drug Administration (FDA) plays a unique role in protecting the
      public health and minimizing the risk of the distribution of unsafe or
      ineffective medicines in the United States. Perhaps equally as important for
      public health, however, is the need for healthcare professionals to be well
      informed about the benefits and risks of the medicines they prescribe. In this
      way, information sharing is critical to healthcare delivery. FDA's current
      interpretation of laws and regulations governing healthcare communications
      prohibits biopharmaceutical companies from sharing certain accurate, data-driven
      information about FDA-approved uses and medically accepted alternative uses of
      FDA-approved drugs with healthcare professionals. Often, these uses are the
      standard of care for good medical practice and are, accordingly, reimbursed under
      the federal healthcare programs. FDA has failed to describe adequately how
      manufacturers can share truthful and non-misleading information about such uses
      with healthcare professionals and formulary decision makers. This failure could
      impede medical innovation, negatively impact patient care, and increase
      healthcare costs. To improve public health, FDA should reform its current
      approach and provide manufacturers with a clear safe harbor on how to share data
      and information on both approved uses and medically accepted alternative uses of
      FDA-approved drugs with healthcare professionals. This Article describes key
      principles for a new regulatory paradigm.

PMID- 26292476
TI  - Can You Diagnose Me Now? A Proposal to Modify FDA's Regulation of Smartphone
      Mobile Health Applications with a Pre-Market Notification and Application
      Database System.
AB  - Mobile applications provide limitless possibilities for the future of medical
      care. Yet these changes have also created concerns about patient safety. Under
      the Federal Food, Drug, and Cosmetic Act (FDCA), the Food and Drug Administration
      (FDA) has the authority to regulate a much broader spectrum of products beyond
      traditional medical devices like stethoscopes or pacemakers. The regulatory
      question is not if FDA has the statutory. authority to regulate health-related
      software, but rather how it will exercise its regulatory authority. In September
      2013, FDA published guidance on Mobile Medical Applications; in it, the Agency
      limited its oversight to a small subset of medical-related mobile applications,
      referred to as "mobile medical applications." For the guidance to be effective,
      FDA must continue to work directly with all actors--including innovators,
      doctors, and patients--as the market for mobile health applications continues to
      develop. This Article argues that FDA should adopt a two-step plan--a pre-market
      notification program and a mobile medical application database--to aid in the
      successful implementation of its 2013 guidance. By doing so, FDA will ensure that
      this burgeoning market can reach its fullest potential.

PMID- 26292477
TI  - Drugs, Devices & Discovery: Using Fee-Shifting to Resolve the Twombly/Iqbal
      Problem for Parallel Claims Under the FDCA.
AB  - The Supreme Court's decisions in Twombly and Iqbal ushered in a new federal
      pleading standard, requiring plaintiffs to state a "plausible" claim to relief
      before they can access discovery. Plausibility pleading, however, presents a
      unique burden for plaintiffs who have been injured by a Class III medical device.
      In Riegel, the Supreme Court held that state-law claims against device
      manufacturers are preempted unless they "parallel" federal requirements. However,
      the relevant federal requirements are located in the manufacturer's premarket
      approval agreement, which is confidential. Thus, it is nearly impossible for
      plaintiffs to allege a plausible claim against a Class III device manufacturer
      because they do not know what to plead in the first place. The Seventh Circuit
      tried to remedy this Catch-22 by lowering the pleading standards for parallel
      claims. However, its approach misapplies Twombly and Iqbal and overburdens device
      manufacturers. Instead of tinkering with pleading standards, this paper advocates
      a different approach. Congress should create a one-way fee-shifting mechanism
      that allows plaintiffs to access premarket approval agreements if they agree to
      pay the defendant's discovery fees (should their claim prove unsuccessful). Fee
      shifting is a middle-ground approach that would better compensate plaintiffs
      without overdeterring device manufacturers.

PMID- 26292478
TI  - Scouting For Approval: Lessons on Medical Device Regulation in an Era of
      Crowdfunding from Scanadu's "Scout".
AB  - Internet crowdfunding, a new and increasingly popular method of raising capital
      to develop products and businesses, has recently come into conflict with the Food
      and Drug Administration's (FDA's) regulation of medical devices. This Article
      examines the issues that arise when companies pre-sell medical devices via
      crowdfunding campaigns before gaining FDA approval of the devices. Because
      Internet crowdfunding has only been in use for a few years, little has been
      written about it academically, particularly about its interaction with FDA
      regulations. The rising interest in crowdfunding, coupled with the downturn in
      investment in the American medical device industry, make this a salient issue
      that is ripe for FDA review. This Article uses the crowdfunding campaign Scanadu,
      a medical device company, conducted in 2013 to raise money to develop its in-home
      diagnostic device, the "Scout," as a starting point for this analysis. Because it
      is extremely costly to develop a device and obtain FDA approval, medical device
      companies should be able to utilize crowdfunding to raise the necessary capital.
      However, because of the possible dangers medical devices pose, FDA needs to
      review the risks created by allowing companies to crowdfund medical devices and
      should issue guidance to help companies comply with FDA regulations while still
      allowing them to take advantage of the benefits of crowdfunding. This guidance
      should ensure the continued commitment to consumer safety that is at the core of
      FDA regulation.

PMID- 26292482
TI  - Medicare Opt-In/Out Infographic Available on ADA Website.

PMID- 26292479
TI  - Celebrate! National Children's Dental Health Month is Here.

PMID- 26292483
TI  - What's a PPO? What's an EPO? Here's the Difference.

PMID- 26292484
TI  - State: Continuing Education Credits Now Available for Volunteering.

PMID- 26292485
TI  - State Program Provides Student Loan Relief; Deadline to Apply Coming Up Soon.

PMID- 26292487
TI  - Regulation of Mobile Dentistry Depends on You.

PMID- 26292489
TI  - 2015 Changes in Sales and Use Tax Filing and Payments.

PMID- 26292490
TI  - Making Deductions to Exempt Employees' Pay.

PMID- 26292491
TI  - Cooking the Books!

PMID- 26292492
TI  - Are You Ready for a Disaster?

PMID- 26292493
TI  - 'Meth Mouth' in a Non-Methamphetamine User.

PMID- 26292494
TI  - Application of the Basic Tenants of Restorative Dentistry in the Management of a
      Patient Post-Maxillectomy.
AB  - PURPOSE: The purpose of this case report is to demonstrate how the basic tenants
      of restorative dentistry can be applied to effectively and comprehensively treat
      a prosthetic rehabilitation after left maxillectomy for a maxillary squamous cell
      carcinoma. MATERIALS AND METHODS: A 55-year-old female presenting with a T1 NOMO
      left maxillary squamous cell carcinoma was treated surgically and restored over a
      3-year period. RESULTS: Restorative treatment involved treatment planning with
      mounted diagnostic casts and diagnostic wax-up to aid sequencing and execution of
      treatment, including the placement of surgical and interim obturators, endodontic
      therapy, fixed prosthodontic restorations, and placement of a definitive
      obturator. CONCLUSION: By using the basic principles of restorative dentistry
      including occlusion and prosthodontics, the restorative rehabilitation of a
      patient presenting with extensive restorative needs in addition to an acquired
      maxillary defect was successful in re-establishing esthetics and function.

PMID- 26292495
TI  - Innovation, Value and Opportunities: What the MDA Accomplished in 2014.

PMID- 26292496
TI  - How to Become a More Effective Business-Owner: 10 Tips.

PMID- 26292497
TI  - Genesee District Dental Society Receives ADA Golden Apple Award.

PMID- 26292498
TI  - Planning for Retirement.

PMID- 26292499
TI  - Legal Ramifications of 'Cooking the Books'.

PMID- 26292500
TI  - Requiring a Hygienist to 'Clock Out' When a Patient Cancels or No-Shows.

PMID- 26292501
TI  - Refusing Pediatric Referrals.

PMID- 26292502
TI  - RETIREMENT: Starting Down a NEW PATH. A time of change for many MDA members.

PMID- 26292503
TI  - Evaluation of Web-Based Interactive Instruction in Intraoral and Panoramic
      Radiographic Anatomy.
AB  - The objective was to evaluate the effectiveness of Web-based interactive modules
      in the instruction of dental hygiene students on intraoral and panoramic
      radiographic landmarks. The experimental group studied these landmarks as
      presented on interactive Web-based modules instead of in classroom presentations.
      The control group (the previous year's class) received instruction in the
      traditional classroom format. The outcomes measures included quizzes,
      examinations and an in-class project. Independent samples t-tests compared the
      scores of the two groups. A survey was administered to the experimental group to
      determine their perceptions of instruction with the modules. There was no
      significant difference in scores between the two groups on the project (p = .926)
      or the intraoral quiz and exam scores (p = .1 22), but the experimental group
      scored significantly lower on the panoramic outcomes (p = .039). Only 26% of the
      students preferred computer-assisted instruction to classroom instruction. The
      narration and interactive quizzes in the intraoral module may have contributed to
      the similar performance of the experimental and control groups, while their
      absence may have adversely affected the effectiveness of the panoramic module.

PMID- 26292505
TI  - Three Leadership Assumptions Dentists Can't Afford to Make.

PMID- 26292504
TI  - To Brazil and Back: An International Dental Student Exchange Program.

PMID- 26292506
TI  - [GLIATILIN CORRECTION OF WORKING AND REFERENCE SPATIAL MEMORY IMPAIRMENT IN AGED
      RATS].
AB  - This work was aimed at evaluating the influence of gliatilin administration on
      the spatial memory in aged rats. Cognitive function and spatial memory in animals
      was evaluated using radial (8-beam) maze test. Errors of working spatial memory
      and reference memory were used as indicators of impaired cognitive function. It
      was found that aged (24-month) rats compared with younger (6-months) age group
      exhibited cognitive impairment, as manifested by deterioration of short- and long
      term memory processes. Course administration of gliatilin in rats of the older
      age group at a dose of 100 mg/kg resulted in significant improvement of the
      working and reference spatial memory in aged rats.

PMID- 26292507
TI  - [STUDYING NEUROPROTECTIVE ACTIVITY OF GABA CONJUGATE WITH ARACHIDONIC ACID UNDER
      CONDITIONS OF LOCAL PERMANENT BRAIN ISCHEMIA IN RATS].
AB  - We have studied the effect of a GABA conjugate with arachidonic acid (AA) on the
      morphological state of rat brain tissues after left median cerebral artery
      occlusion. The results showed that a 6- and 12-day course administration of the
      GABA - AA conjugate at dose of 2 mg/kg (i.p.) in rats with this model of local
      permanent brain ischemia led to significant recovery processes in brain tissues.
      The tissue morphology pattern in the group of animals treated with the GABSA - AA
      conjugate for 12 days was almost identical to that in intact tissues.

PMID- 26292508
TI  - [COMPARATIVE CARDIOPROTECTIVE EFFICACY OF COENZYME Q10 AND MEXICOR IN
      EXPERIMENTAL MODEL OF MYOCARDIAL INFARCTION IN RATS].
AB  - Cardioprotective efficacy of coenzyme Q10 (CoQ10, ubidecarenone) and mexicor were
      evaluated on the 21st day of experimental myocardial infarction in Wistar rats.
      CoQ10 or mexicor were injected in a dose of 30 mg/kg intravenously 10 min after
      coronary artery occlusion. The observed cardioprotective effects of ubidecarenone
      and mexicor were close. Both drugs equally increased the survival of rats,
      prevented the development of dilatation and hypertrophy of the left ventricle,
      and improved the pump cardiac function.

PMID- 26292509
TI  - [ASSESSMENT OF INDICATORS FOR INTERFERON SYSTEM IN PATIENTS WITH COMMON FORMS OF
      PULMONARY TUBERCULOSIS RECEIVING COMPLEX THERAPY WITH CYCLOFERON].
AB  - We have evaluated the efficacy of cycloferon inclusion in the complex therapy of
      newly diagnosed patients with common forms of pulmonary tuberculosis, based on
      monitoring of the number of monocytes with receptors to interferon-gamma (flow
      cytometry) and the concentration of interferon-gamma in the serum (ELISA). For
      this purpose, a group of 36 patients (18 patients received standard chemotherapy,
      and 18 additionally received 600 mg cycloferon tablets 3 times per week) was
      examined for 3 months. Control group consisted of 18 apparently healthy patients.
      The study did not include patients with multiple or extensively drug-resistant M.
      tuberculosis strains. The analysis of results showed a statistically significant
      positive dynamics of the level of monocyte receptors to interferon-gamma in
      patients receiving cycloferon as manifested by an increase in their number in the
      first 2 months of therapy (period of clinical manifestations of the disease),
      followed by a decrease in the 3rd months of treatment, which corresponds to
      clinical improvement, in contrast to patients treated with standard chemotherapy
      alone.

PMID- 26292510
TI  - [PLANNING THE DESIGN AND ESTIMATING THE RESULTS OF INVESTIGATIONS OF
      BIOEQUIVALENCE OF HIGHLY VARIABLE DRUGS BY EXAMPLE OF ROSUVASTATIN].
AB  - The article gives a definition of highly variable drugs, describes currently
      existing regulatory guidance and approaches to the study of bioequivalence of
      highly variable drugs, and formulates recommendations on the design and
      evaluation of the results of studies of such drugs. These aspects are considered
      by the example of calculations based on actual data from the registration
      dossiers materials for rosuvastatin.

PMID- 26292511
TI  - [STUDYING ACUTE TOXICITY OF NEW RADIOPHARMACEUTICAL 99MTC-AL2O3 NANOCOLLOIDS FOR
      ONCOLOGICAL DIAGNOSTICS].
AB  - The acute toxicity of a new drug based on nanocolloidal gamma alumina labeled
      with technetium-99m (99mTc) has been studied on 80 rats (40 females and 40 males)
      and 80 mice (40 females and 40 males) with intraperitoneal and subcutaneous drug
      administration. A single administration of the pharmacological agent was followed
      by observation of the survival of animals for 14 days with determining tolerable,
      toxic, and lethal doses for intraperitoneal and subcutaneous administration
      according to the Litchfield - Wilcoxon method, establishing the causes of animal
      death within 14 days of observation, and studying the drug influence on the
      general condition and some functional and morphological indices. Based on the
      established boundaries of toxicity and the classification of toxicity, the 99mTc
      Al2O3 nanocolloids can be classified into conditionally moderately toxic
      substances. The actual values of LD5 of the radiopharmaceutical fall in the range
      of large doses. The safety factor for the drug studied significantly exceeds the
      minimum permissible value of 100.

PMID- 26292513
TI  - [JUSTIFICATION OF USING EQUIVALENCE OF THE INDICES OF QUALITY, SAFETY, AND
      EFFICACY IN DEVELOPING BIOANALOGS].
AB  - We describe general principles of demonstrating biosimilarity, as well as
      selecting the biosimilarity margins. Any change in the structure of a biological
      molecule can modify its functional activity. Therefore, therapeutic equivalence
      between a biosimilar product and the corresponding reference product cannot be
      demonstrated using a single criterion. To demonstrate biosimilarity between two
      medicinal products, their various characteristics have to be evaluated which may,
      directly or indirectly, justify that clinically significant differences are
      absent. Insufficient understanding of 6ritical quality attributes brings a risk
      for the biosimilar product developer. This will either increase the number of non
      clinical and clinical tests and trials needed or will result in awareness that
      the manufacturing process needs to be improved at the late stages of development,
      after investing significant resources in the development process. At the same
      time, the specification of the biological medicinal product cannot solely ensure
      safety and efficacy thereof. Properly characterized and controlled manufacturing
      process, which ensures consistency in its attributes not adequately controlled in
      specifications but influencing safety and efficacy profiles and showing their
      relevance in non-clinical tests and clinical trials, is an additional quality
      assurance factor. Justification of all development strategy details, including
      biosimilarity margins, has to be provided each time when the development process
      is initiated or when proceeding to the next steps. All problems encountered by
      the developer have to be resolved in close communication with the regulatory
      authority. In order to increase the quality of investigation and developer's
      adherence to good practices, clinical trial results should be published in
      detail.

PMID- 26292512
TI  - [SQUALENE: PHYSIOLOGICAL AND PHARMACOLOGICAL PROPERTIES].
AB  - The review of literature demonstrates that squalene, known to most experts as an
      intermediate product in the synthesis of cholesterol, has several pharmacological
      properties including hypolipidemic, hepatoprotective, cardioprotective,
      antioxidant, and antitoxicant activity. Squalene is effective in the treatment of
      diabetes mellitus type 2 and can potentiate the activity of some antitumor
      (antiblastoma) preparations and reduce their undesired side effects. This
      bioactive substance has low toxicity and, in therapeutic doses, does not produce
      any damaging action on the human organism. A promising source of raw material for
      the commercial production of squalene is offered by amaranth seed oil.

PMID- 26292514
TI  - [DAUGHTERS OF SUN. MANIA, MELANCHOLY AND LOVE SICKNESS IN ANCIENT MYTH AND
      SCIENTIFIC SOURCES].
AB  - Ancient medical and philosophical sources do not discuss the etiology of
      lovesickness, simply cataloguing its symptoms. The 'informal' connection between
      black bile and lovesickness turns, in later texts, into a disease in whick black
      bile overheats, changing its nature (in CH it is a cold and dry element), burning
      and producing smoke. The article analyze this 'ontological' changement; the
      Pseudoaristotelian Problema XXX can help in reconstructing the sense of the
      mythological stories of Pasiphae, Medea, Ariadne and Phaedra, women bound by a
      close family relationship.

PMID- 26292515
TI  - [YESTERDAY'S CLINICIANS: JUDGEMENTS AND REQUESTS IN THREE LETTERS OF NIGRISOLI,
      MURRI, AND GALDI].
AB  - We present here three interesting documents which allow us to have a quick look
      at some aspects of the professional life of Italian teachers of internal medicine
      at the end of XIX century. A typewritten copy of a letter sent, on 23 February
      1877, by Augusto Murri, professor of internal medicine at the University of
      Bologna, to Francesco Crispi, Speaker of the Italian Parliament. This document
      was enclosed in a letter dated 6 March 1937 from Bartolo Nigrisoli, a distingued
      surgeon of Bologna, to Francesco Galdi, clinician of the University of Pisa. The
      third document is a handwritten reply from Galdi to Nigrisoli. Relevant
      information in all three documents are commented upon.

PMID- 26292516
TI  - [ABORTION AND CHARTER FOR THE EMBRYO BETWEEN THE ANCIENT WORLD AND THE THIRD
      MILLENNIUM].
AB  - In 2012 the Italian Court of Cassation recognized a young woman the right not to
      be born and a compensation for her Down's syndrome. Before her birth, her parents
      asked their gynaecologist for abortion in case he had found any patology
      affecting the baby. The clinical tests didn't reveal the syndrome, so, after the
      baby's birth, the doctor was sued for damages. A similar case had occurred in
      France, where the High Court affirmed that constitution is based on the right to
      live, not to die. A debate was opened, in which the hippocratic oath has been
      used to support the pro vita position. This article focuses on whether, when and
      why the hippocratic tradition allows abortion; when and by whom the embryo was
      considered to be a human being; if, according to the few sources we have, a
      charter for the embryo existed in ancient times.

PMID- 26292517
TI  - [BETWEEN HORROR AND SCIENCE: THE BIRTH OF A CABINET OF PATHOLOGICAL ANATHOMY AT
      THE UNIVERSITY OF PALERMO].
AB  - This paper outlines the history of the Cabinet of Pathological Anathomy at the
      University of Palermo, describes rapidly its current status and analyzes the
      composition of its displays in 1859. It aims to highlight the analogies with
      other collections of a similar kind and to pinpoint potential actions to endorse
      and develop this important scientific asset.

PMID- 26292518
TI  - [MALE, FEMALE, NEUTRUM. SEXUAL IDENTITY, UNCERTAIN SEX AND BIOLOGY].
AB  - For almost 2000 years, human beings have been discussing about gender. New
      scientific evidences give interesting new points of view, partially subverting
      the normal dichotomy described by the "two-gender" theory. In this article, we
      are going to critically review the history of the approach towards people born
      with a Sexual-Differentiation-Disorder, passing through the analysis of the
      Italian National Ethics Committee's opinion, describing the modern scientific
      evidences on the gender-identity development, furthermore ruling out the new
      approach borned from the femminist philosophies, and the new biogiuridical
      experiments borned in Australia and Germany. Would it be possible a world where a
      person could be more then a male or a female?

PMID- 26292519
TI  - RICKETS AT THE MEDICI COURT OF FLORENCE: THE CASE OF DON FILIPPINO (1577-1582).
AB  - Among the children found in the crypt of the Grand Duke Giangastone in S. Lorenzo
      Basilica (Florence), the skeletal remains of a 5-year-old child still wearing his
      fine high social status clothing were recovered. This child of the Medici family
      was identified as Don Filippino (1577-1582), son of the Grand Duke Francesco I
      (1541-1587) and Giovanna from Austria (1547 - 1578). The prince showed several
      pathological deformities of the cranial and post-cranial skeleton, including
      enlargement of the cranium, thinning of the cranial vault bones (craniotabes),
      platybasia and marked bending of femora, tibiae and fibulae. Differential
      diagnosis suggests that Don Filippino was affected by rickets. The occurrence of
      this metabolic disease related to vitamin D deficiency in a Renaissance high
      social class individual can be explained by the practice of very prolonged breast
      feeding, up until two years of age. Maternal milk contains insufficient vitamin D
      ratios and retarded weaning severely exposes children to a higher risk of
      developing rickets, especially if dietary habits are combined with inadequate
      exposure to sunlight. Historical sources describe Don Filippino as frail and
      sickly, with frequent illnesses and persistent slight fevers, and it can be
      supposed that the child was frequently confined indoors, especially in the cold
      season. Integration of osteoarchaeological evidence with historical documentation
      suggests that bone lesions observed in the skeletal remains of Don Filippino are
      compatible with a diagnosis of rickets, caused by the custom of prolonged breast
      feeding associated with inadequate sunlight exposure to sunlight. Historical
      sources describe Don Filippino as frail and sickly, with frequent illnesses and
      persistent slight fevers, and it can be supposed that the child was frequently
      confined indoors, especially in the cold season. Integration of
      osteoarchaeological evidence with historical documentation suggests that bone
      lesions observed in the skeletal remains of Don Filippino are compatible with a
      diagnosis of rickets, caused by the custom of prolonged breast-feeding associated
      with inadequate sunlight exposure.

PMID- 26292520
TI  - [AN ETHNOGRAPHIC STUDY OF MEDICAL PRACTICES AND KNOWELEDGE IN THE NAHUA CONTEST (
      NAUPAN, PUEBLA, MEXICO)].
AB  - In the last thirty years, the improvement of biomedical acculturate had
      influenced the medical tradition of Nauha, in souther-eastern Mexico. The study
      analyses how the constituent elements of biomedical tradition are incorporated
      into new rhetorical, diagnostic and therapeutic strategies, mixed with languages
      and symbols typical of local tradition.

PMID- 26292521
TI  - CORRADO GINI AND THE SCIENTIFIC BASIS OF FASCIST RACISM.
AB  - It is controversial whether the development of Fascist racism was influenced by
      earlier Italian eugenic research. Before the First International Eugenics
      Congress held in London in 1912, Italian eugenics was not characterized by a
      clear program of scientific research. With the advent of Fascism, however, the
      equality "number = strength" became the foundation of its program. This idea,
      according to which the improvement of a nation relies on the amplitude of its
      population, was conceived by statistician Corrado Gini (1884-1965) already in
      1912. Focusing on the problem of the degeneration of the Italian race, Gini had a
      tremendous influence on Benito Mussolini's (1883-1945) political campaign, and
      shaped Italian social sciences for almost two decades. He was also a committed
      racist, as documented by a series of indisputable statements from the primary
      literature. All these findings place Gini in a linking position among early
      Italian eugenics, Fascism and official state racism.

PMID- 26292522
TI  - [THE BLADDER STONE OF CARDINAL PIETRO BASADONNA (1617-1684) IN THE WORDS OF HIS
      PHYSICIAN ROMOLO SPEZIOLI (1642-1723)].
AB  - At the death of Cardinal Pietro Basadonna in 1684, his personal physician Romolo
      Spezioli wrote a report describing the disease, circumstances of death and
      autopsy findings of the illustrious prelate. This document, kept in the
      Biblioteca Civica at Jesi, is a significant attestation of the medical
      terminology and diagnostic and therapeutic procedures of the time. Even with the
      constraints that interpretation of a clinical account dating back over 300 years
      inevitably imposes, perusal of this report suggests that Cardinal Basadonna's
      demise could have been due to septic shock, consequent to a urinary infection
      caused by a bulky bladder stone.

PMID- 26292523
TI  - [The international network and Italian modernization. Ruggero Ceppellini,
      genetics, and HLA].
AB  - The paper reconstructs the scientific career of Ruggero Ceppellini, focusing
      especially on his role in the discovery of the genetic system underlying the
      Human Leucocyte Antigen. From his earliest investigations in blood group
      genetics, Ceppellini quickly became an internationally acknowledged authority in
      the field of immunogenetics--the study of genetics by means of immunological
      tools--and participated to the endeavor that ultimately yelded a new meaning for
      the word: thanks to the pioneering research in the HLA field, immunogenetics
      became the study of the genetic control of immune system. The paper will also
      place Ceppellini's scientific work against the backdrop of the modernization of
      Italian genetics after WWII, resulting from the efforts of a handful of
      scientists to connect to international networks and adopting new methodologies in
      life sciences.

PMID- 26292524
TI  - CROSSOVERS BETWEEN EPIGENESIS AND EPIGENETICS. A MULTICENTER APPROACH TO THE
      HISTORY OF EPIGENETICS (1901-1975).
AB  - The origin of epigenetics has been traditionally traced back to Conrad Hal
      Waddington's foundational work in 1940s. The aim of the present paper is to
      reveal a hidden history of epigenetics, by means of a multicenter approach. Our
      analysis shows that genetics and embryology in early XX century--far from being
      non-communicating vessels--shared similar questions, as epitomized by Thomas Hunt
      Morgan's works. Such questions were rooted in the theory of epigenesis and set
      the scene for the development of epigenetics. Since the 1950s, the contribution
      of key scientists (Mary Lyon and Eduardo Scarano), as well as the discussions at
      the international conference of Gif-sur-Yvette (1957) paved the way for three
      fundamental shifts of focus: 1. From the whole embryo to the gene; 2. From the
      gene to the complex extranuclear processes of development; 3. From cytoplasmic
      inheritance to the epigenetics mechanisms.

PMID- 26292526
TI  - Avian Diseases: The Creation and Evolution of P. Philip Levine's Enduring Gift.
AB  - This account has two aims. The first is to provide a tribute to Dr. Pincus Philip
      Levine, the founder of Avian Diseases. It addresses several facets of the life
      and times of this remarkable and interesting personality, giving some insight
      into the why and how he came to establish the journal. It touches on his
      background; his character; his astute and searching mind; his ability to interact
      with others; his influence on veterinary, and especially avian, medicine; and his
      teaching genius and reveals the positive force he was in his interactions with
      others. Then, it turns to a celebration of the first half-century of the journal
      that he created, essentially single-handedly, and reviews some of the history
      regarding the stimulus, birthing pains, and gradual evolution of the journal
      through a succession of editors, business managers, and supporting casts to the
      publication that we see today, nearly 50 yr later.

PMID- 26292527
TI  - Development and Validation of TaqMan Real-Time Polymerase Chain Reaction Assays
      for the Quantitative and Differential Detection of Wild-Type Infectious
      Laryngotracheitis Viruses from a Glycoprotein G-Deficient Candidate Vaccine
      Strain.
AB  - Infectious laryngotracheitis (ILT) is a significant upper respiratory tract
      disease of chickens with a worldwide distribution. Differentiating between wild
      type and vaccine strains of ILT virus (ILTV) would be useful for enhancing
      disease control, and in the early stages of a disease outbreak molecular
      diagnostic tools for the detection and differentiation of the circulating virus
      could be applied. This study developed TaqMan real-time PCR (qPCR) assays to
      detect and differentiate the glycoprotein G (gG)-deficient (DeltagG) ILTV
      candidate vaccine strain of ILTV from ILTV strains that contain the gG gene. The
      gG+ve and gG-ve ILTV TaqMan assays were used in individual and multiplex format
      to detect, differentiate, and quantitate ILTV DNA in laboratory and clinical
      samples. The assays were highly sensitive and highly specific, with a detection
      limit of 10 viral template copies for each assay. Low interassay coefficients of
      variation were recorded (0.021-0.042 and 0.013-0.039) for gG+ve and gG-ve TaqMan
      assays, respectively. The multiplex assay was successfully used to examine the
      replication kinetics of wild-type and DeltagG strains of ILTV in cultured leghorn
      male hepatoma cells and embryonated hen eggs under coinfection conditions. The
      results showed that the TaqMan qPCR assay, along with the DeltagG ILTV vaccine,
      has the potential to be used in a "Differentiating Infected from Vaccinated
      Animals" strategy for the control and eradication of ILT.

PMID- 26292528
TI  - Genotyping and Classification of Tunisian Strains of Avian Reovirus using RT-PCR
      and RFLP Analysis.
AB  - Since 1998, avian reovirus (ARV) infection has been detected in broiler and
      breeding chicken flocks in Tunisia. The genotype of avian reoviruses was
      established using simple and rapid approaches. Reverse transcription PCR (RT-PCR)
      on both sigma C (sigmaC) and sigma B (sigmaB)-encoding genes followed by
      restriction fragment length polymorphism (RFLP) analyses were used to better
      characterize Tunisian isolated strains. The RT-PCR amplified fragments of 738 and
      540 bp for sigmaC- and sigmaB-encoding genes, respectively, of 15 ARV Tunisian
      strains. DNA fragments amplified from S 1133 vaccine and isolated strains were
      digested with different restrictions enzymes. RFLP on the sigmaC gene indicated
      that the field isolates and the S 1133 vaccine strain have identical profiles
      when separately digested with TaqI, PstI, DdeI, and HincII. Considering the
      sigmaB gene, RFLP profiles were identical with RsaI, BclI, DpnII, and NciI
      restriction enzymes for all the strains. However, using MseI and AciI enzymes, it
      was shown that all tested isolates could be clearly distinguished from the
      vaccine strain. ARV strains could be classified in groups with strong
      relatedness. Strain-typing based on cleavage site results are in agreement with
      ARV clustering based on nucleotide sequences of both the sigmaC and sigmaB genes.
      RT-PCR-RFLP provides a simple and a rapid approach for genotyping ARV isolates,
      especially when a large number of isolates are being studied. Additionally, this
      approach may also determine whether a new variant strain has been introduced into
      a flock or if a given virus strain is being spread from one flock to another.

PMID- 26292529
TI  - First Description of an Extended-Spectrum Cephalosporin- and Fluoroquinolone-
      Resistant Avian Pathogenic Escherichia coli Clone in Algeria.
AB  - Eleven avian pathogenic Escherichia coli (APEC) strains isolated from 2006 to
      2010 from different farms in Algeria and resistant to cephalosporins were
      studied. Their susceptibility to antimicrobials was determined by disk diffusion,
      and the genes responsible for resistance to critical antimicrobials were studied
      by PCR, sequencing, and conjugation. Their genetic profiles were compared by
      pulsed-field gel electrophoresis (PFGE). All strains were resistant to extended
      spectrum cephalosporins, ciprofloxacin, tetracycline, trimethoprim
      sulfamethoxazole, and neomycin and showed the same PFGE profile. For most of
      them, resistance was encoded by a nontransferable group 1 bla(CTX-M) gene, and
      multiple mutations were detected in the quinolone resistance-determining regions.
      The clonal dissemination of this resistant APEC is worrying for animal and public
      health.

PMID- 26292530
TI  - Investigations into Outbreaks of Black Fly Attacks and Subsequent Avian
      Haemosporidians in Backyard-Type Poultry and Other Exposed Avian Species.
AB  - In late spring of 2009 and 2010, there were reports of severe black fly (Simulium
      spp., shown in Fig. 1) outbreaks in various counties in Mississippi, especially
      those in and around the Mississippi River Delta. Complaints were of black flies
      attacking multiple species of backyard poultry and causing high morbidity and
      mortality in affected flocks. At several affected locations, black flies were
      readily observed swarming around and feeding on birds. A large number of these
      parasites were easily trapped on fly strips (Fig. 2). Multifocal to coalescing
      cutaneous hemorrhagic lesions, consistent with fly bites, were seen on the birds.
      Upon necropsy examination, a large number of black flies were also observed in
      the digestive tract (Fig. 3). Although black flies may cause disease directly,
      such as cardiopulmonary collapse and anaphylactoid reactions, detection of
      Leucocytozoon in blood smears (Fig. 4) of affected birds prompted further
      investigations of this protozoan as a cause of disease. Leucocytozoon spp. are
      known to be transmitted by black flies and may be associated with morbidity and
      mortality in birds such as poultry. From June 2009 through July 2012, the
      investigation included a total collection of 1068 individual blood samples,
      representing 371 individual premises in 89 counties/parishes across Mississippi
      (59), Alabama (10), Louisiana (4), and Tennessee (16). Of the 371 premises where
      blood samples were collected, 96 (26%) were either positive or highly suspected
      to be positive for Leucocytozoon spp. by blood smear analysis, and 5 (1.2%) were
      positive for Haemoproteus spp. by blood smear analysis. Attempts to diagnose
      Leucocytozoon spp. by PCR analysis and sequencing were complicated by
      coinfections with two closely related haemosporidians (Haemoproteus spp. and
      Plasmodium spp.). A novel technique involving flow cytometry was also explored.
      This study discusses the black fly field outbreak, the involvement of
      haemosporidians, molecular methods for detection of both the black flies and
      blood parasites, and initial attempts at flow cytometry.

PMID- 26292531
TI  - Protection of Neonatal Broiler Chickens Following in ovo Delivery of
      Oligodeoxynucleotides Containing CpG Motifs (CpG-ODN) Formulated with Carbon
      Nanotubes or Liposomes.
AB  - Unformulated oligodeoxynucleotides (ODN) containing CpG motifs (CpG-ODN) have
      been shown to stimulate the innate immune system against a variety of bacterial,
      viral, and protozoan infections in a variety of vertebrate species. We have
      previously shown that in ovo delivery of unformulated CpG-ODN was able to
      significantly protect neonatal broiler chickens against Escherichia coli or
      Salmonella Typhimurium infections. The objectives of this study were to examine
      the safety and immunoprotective effects of CpG-ODN formulated with 2 types of
      carbon nanotubes (CNTs) or 2 types of lipid-surfactant (LSC) delivery systems in
      neonatal broilers against E. coli septicemia. Embryonated eggs, which had been
      incubated for 18 days, received either 50 MUg of CNT-CpG-ODN, 50 MUg of LSC-CpG
      ODN, 50 MUg of unformulated CpG-ODN, or saline. Four days after exposure to CpG
      ODN (day 1 posthatch), 1 x 10(4) or 1 x 10(5) colony-forming units of a virulent
      strain of E. coli isolated from a turkey with septicemia were inoculated
      subcutaneously in the neck. Clinical signs, pathology, bacterial isolations from
      the air sacs, and mortality were observed for 8 days following challenge with E.
      coli. Bacterial isolations and pathologic observations were conducted immediately
      after birds were dead or euthanatized. The survival rate of birds in groups
      receiving saline following E. coli infection was 20% to 30%. In contrast, birds
      receiving CpG-ODN formulations had a significantly higher survival rate of 60% to
      80% (P < 0.01). Bacterial loads and clinical scores were significantly lower (P <
      0.05) in groups treated with CNT- or LSC-CpG-ODN compared to the groups receiving
      CpG-ODN or saline. Moreover, there is no evidence of any adverse effects of these
      formulations in any organs or in growth rates of birds until 42 days of age. This
      is the first time that CpG-ODN formulated with CNT and LSC have been demonstrated
      to have an immunomodulatory effect against an E. coli infection in neonatal
      broiler chickens following in ovo delivery.

PMID- 26292532
TI  - A Multifactorial Analysis of the Extent to Which Eimeria and Fishmeal Predispose
      Broiler Chickens to Necrotic Enteritis.
AB  - Necrotic enteritis (NE) is an important infectious disease in chickens.
      Predisposing factors play critical roles both in disease outbreaks in the field
      and in models for experimental induction of disease. Systematic manipulation and
      study of predisposing factors help to optimize methods for the experimental
      reproduction of disease. The nature of such factors may play a confounding role
      in challenge models and, therefore, warrant investigation to determine their
      importance in industry-relevant NE reproduction models. In the present study, we
      examined the roles of dietary fishmeal inclusion, Eimeria inoculation (E), and
      Clostridium perfringens challenge (C) on broiler growth performance and induction
      of NE infection. The results showed that E, preceding C, greatly increased the
      severity of NE induced in broiler chickens, but fishmeal addition played only a
      marginal role in the challenge model. Bird performance was significantly affected
      by all three factors during the 35-day experimental period. Fishmeal increased
      body weight, but statistically significant effects of fishmeal were not observed
      on feed conversion ratio (FCR) and feed intake. Both Eimeria and C. perfringens
      significantly reduced body weight gain and feed intake. E but not C led to
      significantly poorer FCR. These findings indicate that dietary fishmeal may be
      removed from the model to allow the performance results of challenged chicks to
      be equivalent to the performance of chicks in the field. In conclusion, the
      present study demonstrates that an NE challenge model without fishmeal is valid
      and removes bird performance bias in the model introduced by feeding high
      fishmeal diets, refining the model to facilitate the yield of more commercially
      relevant results.

PMID- 26292533
TI  - Low Prevalence of netB and tpeL in Historical Clostridium perfringens Isolates
      from Broiler Farms in Alabama.
AB  - The discovery of novel Clostridium perfringens toxins NetB and TpeL has initiated
      questions regarding their role in the pathogenesis of disease. However, data
      showing the prevalence of these genes in C. perfringens populations are limited
      to certain geographical areas. If netB and tpeL are important virulence factors
      for disease worldwide, one would expect to find these genes in isolates from
      other regions as well. To address this hypothesis, C. perfringens isolates
      collected from Alabama broiler farms over 15 yr ago were toxin genotyped using
      PCR. Each isolate was screened for netB and tpeL; the major lethal toxin genes
      cpa, cpb, etx, and ia; and the enterotoxin gene cpe. Results of the assay showed
      all isolates presumed to be C. perfringens were genotypically type A, cpe
      negative except for one broiler litter isolate, which was genotypically type C.
      Only two isolates were positive for netB. Similarly, only two isolates were
      positive for tpeL, one of which was also netB positive. The low incidence
      observed for netB and tpeL indicates that these genes are not significant
      virulence factors for the sampled population.

PMID- 26292534
TI  - A Live Oral Fowl Typhoid Vaccine with Reversible O-Antigen Production.
AB  - Salmonella enterica serovar Gallinarum causes fowl typhoid, recognized worldwide
      as an economically important disease. The current vaccine, 9R, lacks a complete O
      antigen, which is a Salmonella virulence factor, and, in addition, has a number
      of other less well characterized chromosomal mutations. For optimal efficacy, 9R
      is administered by injection. In an effort to develop a vaccine suitable for oral
      administration, we constructed Salmonella Gallinarum strains with a reversible O
      antigen phenotype. In this scenario, the vaccine strain produces full-length O
      antigen at the time it is administered to birds. After the vaccine has had time
      to colonize internal lymphoid tissues, the O-antigen is gradually lost, resulting
      in an attenuated strain. We found that strains carrying single mutations
      conferring this phenotype, Apmi and arabinose-regulated rfc, retained virulence.
      However, a mutant strain carrying both of these mutations was completely
      attenuated and immunogenic in chickens. This work demonstrates a novel approach
      for developing live Salmonella vaccines for poultry.

PMID- 26292535
TI  - Characterization of Salmonella from Commercial Egg-Laying Hen Farms in a Central
      Region of Colombia.
AB  - Salmonellosis affects humans more frequently than any other foodborne disease,
      and it causes severe economic losses in the poultry industry. A cross-sectional
      study was carried out to estimate the prevalence of Salmonella spp. in laying hen
      farms in the Tolima region of Colombia. Fifteen egg-laying hen farms were
      sampled, and a total of 589 samples were cultured to isolate Salmonella spp. A
      total of 14 isolates of Salmonella spp. were recovered from five farms, resulting
      in a prevalence of 33.33% (95%, confidence interval = 14%-53%) at the farm level.
      Salmonella spp. were recovered from eggshells (57.15%, n = 8), feed (28.57%, n =
      4), and environmental samples (14.29%, n = 2). Farm practices, such as the
      milling of feed (odds ratio [OR] = 24) and the storage of eggs in the henhouses
      (OR = 11.25), in addition to the feed type (OR = 7.64) and the use of bamboo for
      construction of the facility (OR = 5.24), were identified as risk factors for
      Salmonella spp. The 14 isolates were identified as Salmonella Enteritidis (n = 6)
      and Salmonella Shannon (n = 8), and both serovars were resistant to a number of
      antibiotics. Pulsed-field gel electrophoresis presented three different XbaI
      macrorestriction patterns. The Salmonella Enteritidis isolates all presented a
      single pattern, whereas the Salmonella Shannon isolates were grouped into two
      distinct patterns. The results indicate that Salmonella spp. could be recovered
      from various sources at laying hen farms, and eggshell contamination is a
      particular concern.

PMID- 26292536
TI  - Seroprevalence and Risk Factors for Exposure of Free-Range Poultry to Avian
      Influenza Viruses in Important Bird Areas in Uganda.
AB  - Avian influenza (AI) viruses cause disease in domestic and wild bird species.
      Although these viruses have been reported to occur in poultry in Uganda, risk
      factors for their introduction and spread were largely unknown. We investigated
      the seroprevalence and risk factors for exposure of free-range poultry to AI
      viruses in Important Bird Areas (IBAs) in the country. A structured questionnaire
      was administered to 664 respondents, and 1342 sera were collected from poultry.
      Sera were analyzed for antibody titers against AI using competitive ELISA. AI
      antibody prevalence was 7.6% (95% confidence interval [CI]: 6.2-9.0) in the Lake
      Victoria Basin, 8.4% (95% CI: 7.0-9.8) in the southwestern region, and none
      (0/432) in the Kyoga region. High proportions of risky practices were observed
      among respondent farmers. Significant predictors for exposure of poultry to AI
      viruses were the source of restocking poultry, method of disposal of inedible
      parts of slaughtered poultry, and waterfowl visits to a nearby body of water. In
      addition, visits by waterbirds to a nearby body of water during October-December
      were more associated with exposure to AI viruses (odds ratio = 3.6; 95% CI: 1.42
      9.23) compared with January-March visits'. These results suggested the existence
      of several risk factors for exposure of free-range to AI viruses in IBAs in
      Uganda.

PMID- 26292537
TI  - Efficacy of Five Commonly Used Disinfectants Against Turkey Arthritis Reovirus.
AB  - Since late 2009, an unusual problem of reovirus-related lameness has been seen in
      market-age tom turkeys in the upper Midwest area of the United States. In this
      study, we determined the efficacy of five commonly used disinfectants (Virocid,
      Keno X5, Synergize, One Stroke, and Tek Trol) against turkey arthritis reoviruses
      (TARVs). For comparison, turkey enteric reovirus (TERV) and chicken arthritis
      reovirus (CARV) were also included. At their recommended concentrations, all five
      disinfectants were found to be effective virucidals, inactivating 99.99% of all
      viruses within 10 min. However, oxidizing agents and quaternary ammonium
      compounds + aldehyde types of disinfectants were more effective, killing the
      viruses in a shorter time (2-5 min) than the other types of disinfectants. These
      results indicate that these disinfectants can be an effective tool in the control
      of these viruses.

PMID- 26292538
TI  - Effects of the Physical Form of Diet on the Outcome of an Artificial Salmonella
      Infection in Broilers.
AB  - To prove the hypothesis that the physical form of diet affects the outcome of an
      artificial infection with Salmonella Enteritidis in broilers, 7-day-old birds
      were allotted to one of four groups and fed botanically, and nearly also
      chemically identical diets, differing in grinding and further compaction. In
      total, two birds from each group (age 14 days) were administered on average 1.06
      x 10(8) colony-forming units (CFU) of Salmonella Enteritidis directly into the
      crop by gavage and immediately put back as "seeder birds" into their respective
      groups. The salmonella status of each bird was analyzed by cloacal swabs, and at
      postmortem examination, cecal content and liver tissue samples were taken.
      Shedding (measured by cloacal swabs) was reduced significantly (P < 0.05) in
      groups offered the coarsely ground and pelleted diet and the diet including whole
      wheat compared with the groups fed the finely ground and pelleted and the
      coarsely ground and extruded diet. Nevertheless, only broilers fed the diet
      containing whole wheat showed a significantly (P < 0.05) lower frequency of
      Salmonella Enteritidis isolation in the cecal content and liver tissue. This diet
      was characterized by the highest percentage of particles > 2 mm. In this study
      the physical form of diet affected the outcome of an artificial infection with
      Salmonella Enteritidis significantly.

PMID- 26292539
TI  - Isolation and Characterization of IgM and IgY Antibodies from Plasma of
      Magellanic Penguins (Spheniscus magellanicus).
AB  - Infectious diseases such as aspergillosis, avian malaria, and viral infections
      are significant threats to the conservation of penguins, leading to morbidity and
      mortality of these birds both in captivity and in the wild. The immune response
      to such infectious diseases is dependent on different mechanisms mediated by
      cells and soluble components such as antibodies. Antibodies or immunoglobulins
      are glycoproteins that have many structural and functional features that mediate
      distinct effector immune functions. Three distinct classes of antibodies have
      been identified in birds: immunoglobulin A (IgA), immunoglobulin M (IgM), and
      immunoglobulin Y (IgY). In this study we aim to establish an efficient laboratory
      method to obtain IgM and IgY antibodies from plasma samples of healthy adult
      Magellanic penguins (Spheniscus magellanicus). The protocol was developed
      combining plasma delipidation, sequential precipitation with caprylic acid and
      ammonium sulfate, and size-exclusion chromatography. The efficiency of the
      protocol and the identity of the purified IgM and IgY antibodies were confirmed
      through enzyme-linked immunosorbent assay, Western blotting, one-dimensional and
      two-dimensional polyacrylamide gel electrophoresis, and lectin binding assay.
      Structural and physicochemical properties of IgM and IgY from Magellanic penguins
      were consistent with those of other avian species. This purification protocol
      will allow for more detailed studies on the humoral immunity of penguins and for
      the development of high specificity serologic assays to test Magellanic penguins
      for infectious pathogens.

PMID- 26292540
TI  - Loss of the Capsule Increases the Adherence Activity but Decreases the Virulence
      of Avibacterium paragallinarum.
AB  - Avibacterium paragallinarum is the causative agent of infectious coryza, an
      important respiratory disease of chickens. The capsule is an important virulence
      determinant of many pathogenic bacteria, but the function of the capsule in Av.
      paragallinarum is not well defined. In this study, acapsular mutants of Av.
      paragallinarum were constructed by inactivation of the hctA gene using the
      TargeTron gene knockout system. The acapsular mutants were found to have greater
      hemagglutination activity than did the wild-type strain. Further, acapsular
      mutants exhibited an increased ability to adhere to DF-1 cells and to form
      biofilms on abiotic surfaces. Virulence assays showed that acapsular mutants were
      less virulent than the wild-type strain. Taken together, these results indicated
      that loss of capsule increases hemagglutination and adhesion activities but
      decreases the virulence of Av. paragallinarum. These results could be valuable to
      further elucidate the function of the capsule and the mechanism of pathogenicity
      of Av. paragallinarum.

PMID- 26292541
TI  - The Mut UL5-I682R Marek's Disease Virus with a Single Nucleotide Mutation Within
      the Helicase-Primase Subunit Gene not only Reduces Virulence but also Provides
      Partial Vaccinal Protection Against Marek's Disease.
AB  - Marek's disease virus (MDV) is an oncogenic herpesvirus that afflicts chickens
      with the disease known as Marek's disease (MD). This virus induces tumors, nerve
      lesions, immunosuppression, and death of affected birds. Vaccines are the primary
      control method for MD but, due to the periodic evolution of field strains, it is
      necessary to explore the development of new MD vaccines. MD vaccines are often
      attenuated MDV strains generated through serial passage in vitro. We previously
      used experimental evolution of MDV to provide a better understanding of the
      genetic basis of attenuation. During complete genome sequencing of evolved MDV
      populations, we identified a point mutation within the UL5 helicase-primase gene
      and created a UL5 recombinant virus that significantly reduced disease incidence
      by 89%-100%. To determine if experimental evolution also identifies mutations
      that provide protective qualities as potential vaccine candidates, we tested the
      UL5 recombinant virus as a vaccine and compared its protection to commercial
      herpesvirus of turkey (HVT) and bivalent (HVT + SB-1) vaccines. Both commercial
      vaccines resulted in higher protection against MD than did the UL5 recombinant
      virus, although the UL5 virus did provide protection against developing MD in 46%
      70% of birds challenged. This indicates that a mutation within the UL5 helicase
      primase gene not only reduces virulence but also confers protection against
      challenge with virulent MDV, providing support that not only can experimental
      evolution identify candidate mutations involved in attenuation but can also
      identify potential candidates for use in vaccine development.

PMID- 26292542
TI  - Protection of Broiler Chicks Housed with Immunized Cohorts Against Infection with
      Eimeria maxima and E. acervulina.
AB  - The use of live oocyst vaccines is becoming increasingly important in the control
      of avian coccidiosis in broilers. Knowledge of the mechanisms employed when
      chicks uptake oocysts and become immune is important for optimizing delivery of
      live vaccines. The current study tests the hypothesis that chicks not initially
      immunized may ingest oocysts by contact with litter containing oocysts shed by
      immunized cohorts. In Experiment 1, day-old broiler chicks were housed in pens
      containing clean litter. In Trial 1, 100% of chicks in some pens were immunized
      with 2.5 X 10(3) Eimeria acervulina oocysts while in other pens only 75% of
      chicks were immunized and remaining cohorts within the pens were not immunized.
      Other pens contained chicks that served as nonimmunized nonchallenged controls or
      nonimmunized challenged controls (NIC). On day 21, birds were given a homologous
      challenge of 6 X 10(5) oocysts. A second identical trial was conducted, except
      birds were immunized with 500 Eimeria maxima oocysts and were challenged with 3 X
      10(3) E. maxima oocysts. In Experiment 2, 100% of chicks in some pens were
      immunized with 500 E. acervulina oocysts while in other pens either 75% or 50% of
      the birds were immunized. On day 14, birds were challenged with 1 X 10(6)
      oocysts. Trial 2 was identical to Trial 1 except that birds were immunized with
      100 E. maxima oocysts and challenged with 1 X 10(6) oocysts. For all experiments
      weight gain, feed conversion ratio (FCR), plasma carotenoids, and litter oocyst
      counts were measured. In Experiment 1, the level of protection in groups
      containing 25% nonimmunized cohorts, as measured by weight gain, carotenoid
      level, FCR, and oocyst litter counts, was identical to groups containing 100%
      immunized chicks. In Experiment 2, pens where 50% or 75% of birds were immunized
      with either E. maxima or E. acervulina were not well protected from decreases in
      weight gain and plasma carotenoids nor from increases in litter oocyst counts
      following a challenge infection administered on day 14 relative to NIC. In
      addition, pens of birds where 100% of chicks were immunized were not well
      protected compared to NIC, and resistance to coccidiosis infection in immunized
      chicks was less than resistance in chicks challenged at 21 days. These results in
      total suggest that, when birds are challenged after 21 days, cohorts are
      protected from detrimental effects of challenge infection. However, when
      challenge infection is given at 14 days, cohorts are not well protected. The
      results support a conclusion that protection to coccidiosis is conveyed to
      cohorts by contact with oocysts shed into the litter by immunized chicks, but
      this resistance may take 14 days to develop.

PMID- 26292543
TI  - Effects of Adaptation of Infectious Bronchitis Virus Arkansas Attenuated Vaccine
      to Embryonic Kidney Cells.
AB  - The population structure of an embryo-attenuated infectious bronchitis virus
      (IBV) Arkansas (Ark) Delmarva Poultry Industry (DPI)-derived vaccine was
      characterized during serial passages in chicken embryo kidney (CEK) cells and
      after back-passage in embryonated chicken eggs (ECE) and in chickens. Both
      conventional and deep-sequencing results consistently showed population changes
      occurred during adaptation to CEK cells. Specifically, 13 amino acid (aa)
      positions seemed to be targets of selection when comparing the vaccine genome
      prior to and after seven passages in CEK (CEKp7). Amino acid changes occurred at
      four positions in the spike (S) gene and, at two positions in the S gene, large
      shifts in frequencies of aa encoding were observed. CEK adaptation shifted the
      virus population towards homogeneity in S. The changes achieved in the S1 gene in
      CEKp7 were maintained after a back-passage in ECE. Outside the S gene, aa changes
      at three positions and large shifts in frequencies at four positions were
      observed. Synonymous nucleotide changes and changes in noncoding regions of the
      genome were observed at eight genome positions. Inoculation of early CEK passages
      into chickens induced higher antibody levels and CEKp4 induced increased
      respiratory signs compared to CEKp7. From an applied perspective, the fact that
      CEK adaptation of embryo-attenuated Ark vaccines reduces population
      heterogeneity, and that changes do not revert after one replication cycle in ECE
      or in chickens, provides an opportunity to improve commercial ArkDPI-derived
      vaccines.

PMID- 26292545
TI  - The Influence of Major Histocompatibility Complex and Vaccination with Turkey
      Herpesvirus on Marek's Disease Virus Evolution.
AB  - Over the last five decades, the pathogenicity of the Marek's disease virus (MDV)
      has evolved from the relatively mild strains (mMDV) observed in the 1960s to the
      more severe very-virulent-plus strains currently observed in today's outbreaks.
      The use of vaccines to control Marek's disease (MD), but not the infection cycle,
      is thought to be the major influence on the evolution of MDV. Selection for
      genetic resistance to MD has also been employed by the industry to control MD in
      the commercial setting but the role of host genetics on the evolution of MDV has
      been difficult to investigate in the field. To investigate the influence of
      vaccination and host resistance we developed a laboratory model to control and
      assess the effects of virus and animal genetics on MDV evolution. A bacterial
      artificial chromosome-derived MDV (Md5B40BAC) was used for in vivo passage (IVP)
      through turkey herpesvirus (HVT)-vaccinated resistant (MHC-B21) and susceptible
      (MHC-B13) genetic chicken lines. During IVP in the vaccinated susceptible line,
      the disease incidence increased from 23% MD in the first IVP to 53% MD during the
      fifth IVP. In the vaccinated resistant line, disease incidence increased from 0%
      MD during the first IVP to 29% MD during the fifth IVP. Although the IVP isolates
      remained relatively mild in the vaccinated resistant chicken line (29% MD) they
      increased from 0% to 63% MD when used to challenge the vaccinated susceptible
      chickens. There was no corresponding increase in disease incidence when the virus
      passed in the vaccinated susceptible genetic line was used to challenge the
      vaccinated resistant line. From this series of experiments we show that a cloned
      MDV (Md5B40BAC) can be selected by serial IVP to induce greater disease incidence
      in vaccinated chickens. This increase in disease incidence occurs in both
      susceptible and resistant chicken lines but is more easily observed in the
      susceptible line. Not surprisingly, both host genetics and vaccination play a
      role in selecting for increased MDV virulence. Our results suggest that the
      progressive increase in MDV virulence is partially masked as it circulates
      through vaccinated resistant genetic lines, but by applying this virus to less
      resistant genetic lines, virus evolution can be clearly observed. We would
      predict that the introduction of more-resistant genetic lines into a commercial
      house contaminated with MDV circulating through susceptible lines would be less
      likely to produce vaccine breaks than placing susceptible lines into a house in
      which previously the MDV was circulating through resistant genetic lines.

PMID- 26292544
TI  - Efficacy, Safety, and Interactions of a Live Infectious Bursal Disease Virus
      Vaccine for Chickens Based on Strain IBD V877.
AB  - Infectious bursal disease (IBD) is a highly contagious disease in young chickens
      which can result in high morbidity and mortality and also in great economic
      losses. The main target for the virus is the lymphoid tissue with a special
      predilection for the bursa of Fabricius. Several vaccines are available to
      control the disease. Intermediate plus vaccines are used in chickens with high
      maternal antibody titers which face high infection pressure. An example of an
      intermediate plus vaccine is a live vaccine based on IBD strain V877. The results
      of an efficacy study in commercial broilers with different levels of maternally
      derived antibodies (MDA) showed that the V877-based IBD vaccine can break through
      maternal antibody titers of higher than 1100 as determined by an IBD ELISA. The
      safety of the vaccine was demonstrated in a study in which specific-pathogen-free
      (SPF) chickens were vaccinated with a tenfold dose of the vaccine strain and a
      tenfold dose of the vaccine strain after five back passages in SPF chickens. The
      vaccine virus caused lesions, as could be expected for an intermediate plus
      vaccine, but the scores were not much higher than the maximal scores allowed for
      mild IBD vaccines in the European Pharmacopoeia, and reversion to virulence was
      absent. In studies in SPF chickens, there were no negative impacts by the IBD
      V877 vaccine on the efficacy of a live QX-like IB vaccine and a live Newcastle
      disease La Sota vaccine in vaccination challenge studies, although the IBD
      vaccine had a negative effect on the antibody response generated by the QX-like
      IB vaccine. It is concluded that the IBD V877 vaccine has the capacity to break
      through high levels of MDA, has a satisfactory safety profile, and interactions
      with other live vaccines are limited. In order to limit bursal lesions after
      vaccination it is recommended to confirm the presence of MDA before vaccinating
      with the V877 vaccine.

PMID- 26292546
TI  - Retrospective Study on the Isolation of Ornithobacterium rhinotracheale from
      Chickens and Turkeys in Central California: 294 cases (2000-12).
AB  - Ornithobacterium rhinotracheale is a rod-shaped, gram-negative, and mostly
      oxidase-positive bacterium that causes respiratory infections in chickens and
      turkeys worldwide and can also spread to nonrespiratory organs. The present
      report analyzes 294 cases in which O. rhinotracheale was isolated from turkeys or
      chickens in central California in the years 2000 through 2012. Two hundred
      sixteen cases were from turkey flocks and 78 from chicken flocks. The median age
      of turkey flocks was 8.7 wk; the median age of chicken flocks was 6.4 wk. From
      turkeys, O. rhinotracheale was more often isolated from August to January than
      during the rest of the year. Chickens cases were more evenly distributed
      throughout the year. The organs with the highest isolation rate were the
      infraorbital sinus and trachea, followed by lungs and air sacs. Isolation from
      other organs was rare. Pure cultures were obtained from relatively more turkey
      organs than chicken organs. The organ from which there was the highest chance to
      obtain a pure culture was the air sac. In 108 turkey flocks (50.0%) and 64
      chicken flocks (82.1%) at least one other respiratory pathogen was detected. The
      most common gross lesions were increased mucus in trachea, caseous or fibrinous
      exudate in the air sacs, consolidated lungs indicating pneumonia, congested and
      edematous lungs, and a flattened trachea. For most types of lesions, the
      percentage of affected turkeys was higher than the percentage of affected
      chickens. The percentage of birds with lesions was higher if other respiratory
      pathogens were present. Overall, the host species (turkey or chicken) was a more
      important factor for the prevalence of most lesions than the detection of other
      respiratory pathogens. The most common histopathologic lesions in the sinus and
      trachea were heterophilic or mononuclear inflammatory cell infiltration. In the
      lungs and air sacs, the inflammation was characterized by heterophilic
      infiltration and/or fibrin accumulation. These results are helpful in selecting
      the most appropriate samples for isolation of O. rhinotracheale. In addition,
      they show the incidence of the bacterium in turkeys and chickens and which
      lesions can be expected after infection with O. rhinotracheale, and they indicate
      that in some cases O. rhinotracheale can be the primary, or at least the major,
      pathogen.

PMID- 26292547
TI  - Investigating Turkey Enteric Picornavirus and Its Association with Enteric
      Disease in Poults.
AB  - Previous research into the viral community in the poultry gastrointestinal tract
      has revealed a number of novel and partially described enteric viruses. It is
      evident that the poultry gut viral community remains minimally characterized and
      incompletely understood. Investigations into the microbiome of the poultry gut
      have provided some insight into the geographical distribution and the rapidly
      evolving taxonomy of the avian enteric picornaviruses. The present investigation
      was undertaken to produce a comparative metagenomic analysis of the gut virome
      from a healthy turkey flock versus a flock placed in the field. This
      investigation revealed a number of enteric picornavirus sequences that were
      present in the commercial birds in the field that were completely absent in the
      healthy flock. A novel molecular diagnostic assay was used to track the shedding
      of field strains of turkey enteric picornavirus in commercial poults inoculated
      with picornavirus-positive intestinal homogenates prepared from turkeys that were
      experiencing moderate enteric disease. The propagation of this novel enteric
      picornavirus in commercial poults resulted in significant reduction in weight
      gain, and suggests that this common inhabitant of the turkey gut may result in
      performance problems or enteric disease in the field.

PMID- 26292548
TI  - Antimicrobial Susceptibility Patterns of Enterococcus faecalis and Enterococcus
      faecium Isolated from Poultry Flocks in Germany.
AB  - Between 2010 and 2011, 145 Enterococcus isolates (Enterococcus faecalis, n = 127;
      Enterococcus faecium, n = 18) were collected during routine bacteriologic
      diagnostics from broilers, layers, and fattening turkeys in Germany showing
      various clinical signs. The susceptibility to 24 antimicrobial agents was
      investigated by broth microdilution test to determine minimum inhibitory
      concentrations (MICs). All E. faecalis isolates (n = 127) were susceptible to the
      beta-lactam antibiotics ampicillin, amoxicillin-clavulanic acid, and penicillin.
      Corresponding MIC with 50% inhibition (MIC50) and MIC with 90% inhibition (MIC90)
      values of these antimicrobial agents were at the lower end of the test range (<=
      4 MUg/ml). In addition, no vancomycin-resistant enterococci (VRE) were found.
      High resistance rates were identified in both Enterococcus species for lincomycin
      (72%-99%) and tetracycline (67%-82%). Half or more than half of Enterococcus
      isolates were resistant to gentamicin (54%-72%) and the macrolide antibiotics
      erythromycin (44%-61%) and tylosin-tartate (44%-56%). Enterococcus faecalis
      isolated from fattening turkeys showed the highest prevalence of antimicrobial
      resistance compared to other poultry production systems. Eighty-nine out of 145
      Enterococcus isolates were resistant to three or more antimicrobial classes.
      Again, turkeys stood out with 42 (8 1%) multiresistant isolates. The most
      frequent resistance patterns of E. faecalis were gentamicin, lincomycin, and
      tetracycline in all poultry production systems.

PMID- 26292549
TI  - Hatchery Spray Cabinet Administration Does Not Damage Avian Coronavirus
      Infectious Bronchitis Virus Vaccine Based on Analysis by Electron Microscopy and
      Virus Titration.
AB  - studies in our laboratory showed that the Arkansas-Delmarva Poultry Industry (Ark
      DPI) vaccine given to 1-day-old chickens by hatchery spray cabinet replicated
      poorly and failed to adequately protect broilers against homologous virus
      challenge, whereas the same vaccine given by eye-drop did replicate and the birds
      were protected following homologous virus challenge. To determine if mechanical
      damage following spray application plays a role in failure of the Ark-DPI
      vaccine, we examined the morphology of three Ark-DPI vaccines from different
      manufacturers using an electron microscope and included a Massachusetts (Mass)
      vaccine as control. One of the Ark-DPI vaccines (vaccine A) and the Mass vaccine
      had significantly (P < 0.005) fewer spikes than the other two Ark-DPI vaccines.
      We also found that the Ark-DPI and Mass vaccines had significantly (P < 0.005)
      fewer spike proteins per virus particle when compared to their respective
      challenge viruses. This observation is interesting and may provide some insight
      into the mechanism behind infectious bronchitis virus attenuation. No obvious
      differences were observed in virus morphology and no consistent trend in the
      number of spikes per virion was found in before- and after-spray samples. We also
      determined the vaccine titer before and after spray in embryonated eggs and found
      that both Ark-DPI and Mass vaccines had a similar drop in titer, 0.40 logi and
      0.310 logi, respec10ively. Based on these data, it appears that mechanical damage
      to the Ark-DPI vaccine is not occurring when delivered by a hatchery spray
      cabinet, suggesting that some other factor is contributing to the failure of that
      vaccine when given by that method.

PMID- 26292550
TI  - Persistence and Tissue Distribution of Infectious Bursal Disease Virus Serotypes
      1 and 2 in Turkeys.
AB  - Two experiments were conducted to determine the persistence and tissue
      distribution of serotypes 1 and 2 of infectious bursal disease virus (IBDV) in
      specific-pathogen-free and vaccinated turkeys. In Experiment 1, three groups of 2
      wk-old turkey poults, including a negative control group, were used. In groups 1
      and 2, 13 poults in each group were challenged with either serotype 1 (STC) or
      serotype 2 (OH) strains using an inoculum of 10(4) 50% embryo infectious dose
      (EID50)/0.2 ml/bird. Thymus, bursa, spleen, kidney, lungs, liver, pancreas,
      caecum, and breast and thigh muscles were sampled at predetermined intervals. The
      bursal tissues from birds inoculated with either serotype were reverse
      transcriptase-PCR (RT-PCR) positive up to 21 days postinoculation (DPI). In both
      groups virus isolation from bursas was possible up to 14 DPI. Except for the
      bursas and spleens in birds inoculated with serotype 1 and bursas in birds
      inoculated with serotype 2, all other tissues were RT-PCR negative. In Experiment
      2, five groups of turkey poults were used. At 4 wk of age, group 1 was challenged
      with a serotype 1 STC strain and group 2 with serotype 2 OH strain using an
      inoculum size of 10(2) EID50/0.2 ml for both serotypes. Groups 3 and 4 were
      vaccinated at 2 wk of age using an inactivated serotype 1 IBDV vaccine. At 2 wk
      postvaccination, groups 3 and 4 were challenged with STC and OH strains
      respectively. From group 1, bursal, spleen, and liver tissues were RT-PCR
      positive up to 14 DPI; breast muscle and kidney tissues were positive up to 7
      DPI; and lungs and pancreatic tissues were positive up to 3 DPI. From group 2,
      bursal tissues were RT-PCR positive up to 14 DPI and lung tissues up to 3 DPI.
      All of the tissue samples collected from groups 3, 4, and 5 were RT-PCR negative.
      Virus could not be isolated from RT-PCR positive bursal homogenate. In this work,
      it was confirmed that the virus persisted in the bursa longer than in any other
      tissues. The difference in the results between Experiments 1 and 2 could be due
      to the age of poults at vaccination and the higher inoculum size used in
      Experiment 1. This study indicates that turkeys are more resistant to IBDV as
      compared to chickens. Viruses of serotypes 1 and 2 infect turkeys and persist in
      bursal tissue for 14 days and RNA was detected up to 21 days.

PMID- 26292551
TI  - Host Specificity and Phylogenetic Relationships of Chicken and Turkey
      Parvoviruses.
AB  - Inoculation of specific-pathogen-free chickens and turkeys with five chicken
      parvoviruses (ChPV) and five turkey parvoviruses (TuPV) resulted in productive
      virus replication only in the homologous host species. A phylogenetic tree based
      on nucleotide sequences of the VP1 gene segment revealed a host-specific
      clustering of the virus strains. These results suggest that the VP1 gene plays an
      essential role in host specificity of ChPV and TuPV strains and could be a
      relevant target sequence for strain classification.

PMID- 26292552
TI  - Protection Conferred by Infectious Coryza Vaccines Against Emergent Avibacterium
      paragallinarum Serovar C-1.
AB  - Infectious coryza is an upper respiratory disease of chickens caused by
      Avibacterium paragallinarum. Outbreaks of infectious coryza caused by Av.
      paragallinarum serovar C-1 isolates in coryza-vaccinated flocks in Ecuador and
      Mexico have been reported. In the current study, the protection conferred by four
      commercially available, trivalent infectious coryza vaccines in chickens
      challenged with a serovar C-1 isolate from an apparent coryza vaccine failure in
      a layer flock in Mexico was evaluated. Only one infectious coryza vaccine
      provided a good protection level (83%) in vaccinated chickens. These results
      might explain the infectious coryza outbreaks in vaccinated flocks that have been
      observed in the field.

PMID- 26292553
TI  - Electron-Beam-Inactivated Vaccine Against Salmonella Enteritidis Colonization in
      Molting Hens.
AB  - Electron-beam (eBeam) irradiation technology has a variety of applications in
      modern society. The underlying hypothesis was that eBeam-inactivated Salmonella
      enterica serovar Enteritidis (SE) cells can serve as a vaccine to control SE
      colonization and shedding in poultry birds. An eBeam dose of 2.5 kGy (kilograys)
      was used to inactivate a high-titer (10(8) colony-forming units [CFU])
      preparation of SE cells. Microscopic studies revealed that the irradiation did
      not damage the bacterial cell membranes. The vaccine efficacy was evaluated by
      administering the eBeam-killed SE cells intramuscularly (1 x 10(6) CFU/bird) into
      50-wk-old single comb white leghorn hens. On day 14 postvaccination, the hens
      were challenged orally with live SE cells (1 x 10(9) CFU) and SE colonization of
      liver, spleen, ceca, and ovaries determined on day 23. Blood samples were
      collected on days 0, 14, and 23 postvaccination and the sera were analyzed to
      quantify SE-specific IgG titers. The vaccinated chickens exhibited significantly
      (P < 0.0001) higher SE-specific IgG antibody responses and reduced SE ceca
      colonization (1.46 +/- 0.39 logi10 CFU/g) compared to nonvaccinated birds (5.32
      +/- 0.32 log10 CFU/g). They also exhibited significantly lower SE colonization of
      the ovaries (1/30), spleen (3/30), liver (4/30), and ceca (7/30) compared to
      nonvaccinated birds. These results provide empirical evidence that eBeam-based SE
      vaccines are immunogenic and are capable of protecting chickens against SE
      colonization. The advantages of eBeam-based vaccine technology are that it is
      nonthermal, avoids the use of formalin, and can be used to generate inactivated
      vaccines rapidly to address strain-specific infections in farms or flocks.

PMID- 26292554
TI  - Mature Turkey Breeder Hens Exposed to Pandemic Influenza H1N1: Resultant Effects
      on Morbidity, Mortality, and Fecundity.
AB  - During the artificial insemination process, turkey breeder hens may become
      infected with influenza virus acquired from humans. The virus has been shown,
      through experimental infection, to localize in the reproductive tract, with
      limited dissemination in other tissues. A limited number of hens were used during
      these studies, and the overall flock morbidity, mortality, and fecundity were not
      able to be determined. The current case follows the progression of clinical signs
      in a flock of commercial breeder hens from onset of egg production losses in one
      house through the subsequent drops in four remaining houses. Each house contained
      approximately 3000 hens and followed a sequential loss of shell quality, reduced
      numbers of eggs, and fertility, while mild clinical signs were observed and
      mortality was slightly increased in a house with concurrent fowl cholera
      (Pasturella multocida) infection.

PMID- 26292555
TI  - Pathological Evaluation of Natural Cases of a Highly Pathogenic Avian Influenza
      Virus, Subtype H5N8, in Broiler Breeders and Commercial Layers in South Korea.
AB  - Outbreaks of highly pathogenic avian influenza (HPAI) virus, subtype H5N8, were
      observed in two different flocks of local broiler breeder farms and a commercial
      layer farm in South Korea. Clinically, the cases were characterized by a gradual
      increase in mortality, slow transmission, and unrecognizable clinical signs of
      HPAI. Gross observations in both cases included hemorrhagic or necrotic lesions
      in internal organs, such as serosal and mucosal membranes, spleen, and pancreas.
      Both cases exhibited similar histopathologic lesions, including multifocal
      malacia in the brain and multifocal or diffuse necrosis in the spleen and
      pancreas. Immunohistochemical results indicated that neurons and glial cells in
      the brain, myocytes in the heart, acinar cells in the pancreas, and mononuclear
      phagocytic cells in several visceral organs were immunopositive for avian
      influenza viral antigen. To experimentally reproduce the low pathogenicity and
      the mortality observed in these two cases, 18 specific-pathogen-free chickens and
      18 commercial layers were divided into an H5N8 virus-inoculated group and a
      contact-exposed group. The mortality of the chickens in the inoculation group was
      50%-100%, whereas the mean time to death was delayed or death did not occur in
      the contact-exposed group. The distributions of the viral antigens and
      histopathologic lesions in the experimental study were similar to those observed
      in the field cases. These findings suggest that the H5N8 virus induces a
      different pattern of pathobiology, including slow transmission and low mortality,
      compared with that of other HPAI viruses. This is the first pathologic
      description of natural cases of H5N8 in South Korea, and it may be helpful in
      understanding the pathobiology of novel H5N8 HPAI viruses.

PMID- 26292556
TI  - 'The Senja Doctor': developing joint GP services among rural communities in
      Northern Norway.
AB  - Senja, the second largest island in Norway, encompasses four municipalities. For
      decades the island has faced serious challenges concerning recruiting and
      retaining general practitioners (GPs). In 2001 the county medical officer
      suggested a plan for improvement of GP service based on inter-municipal
      collaboration. The plan was rejected by the three small and remote municipalities
      of Senja. In 2007, after further deterioration of the situation, one of the small
      municipalities initiated a process to establish a joint service. This was very
      similar to the one previously proposed by the county medical officer. Within the
      next few years all the municipalities gradually announced their interest in the
      development of Senjalegen - the Senja Doctor - an inter-municipal GP service.
      This has resulted in improved continuity of GP care to the population of Senja.
      In this article we present experiences and discuss effects of creating a robust
      professional environment securing support and guidance of young doctors. The
      importance of local involvement and ownership during development of a joint
      healthcare service is also discussed.

PMID- 26292557
TI  - Gold nanoprobe-based non-crosslinking hybridization for molecular diagnostics.
AB  - Non-crosslinking (NCL) approaches using DNA-modified gold nanoparticles for
      molecular detection constitute powerful tools with potential implications in
      clinical diagnostics and tailored medicine. From detection of pathogenic agents
      to identification of specific point mutations associated with health conditions,
      these methods have shown remarkable versatility and simplicity. Herein, the NCL
      hybridization assay is broken down to the fundamentals behind its assembly and
      detection principle. Gold nanoparticle synthesis and derivatization is addressed,
      emphasizing optimal size homogeneity and conditions for maximum surface coverage,
      with direct implications in downstream detection. The detection principle is
      discussed and the advantages and drawbacks of different NCL approaches are
      discussed. Finally, NCL-based applications for molecular detection of clinically
      relevant loci and potential integration into more complex biosensing platforms,
      projecting miniaturization and portability are addressed. 

PMID- 26292558
TI  - Understanding information synthesis in oral surgery for the design of systems for
      clinical information technology.
AB  - An understanding of the processes of clinical decision-making is essential for
      the development of health information technology. In this study we have analysed
      the acquisition of information during decision-making in oral surgery, and
      analysed cognitive tasks using a "think-aloud" protocol. We studied the
      techniques of processing information that were used by novices and experts as
      they completed 4 oral surgical cases modelled from data obtained from electronic
      hospital records. We studied 2 phases of an oral surgeon's preoperative practice
      including the "diagnosis and planning of treatment" and "preparing for a
      procedure". A framework analysis approach was used to analyse the qualitative
      data, and a descriptive statistical analysis was made of the quantitative data.
      The results showed that novice surgeons used hypotheticodeductive reasoning,
      whereas experts recognised patterns to diagnose and manage patients. Novices
      provided less detail when they prepared for a procedure. Concepts regarding
      "signs", "importance", "decisions", and "process" occurred most often during
      acquisition of information by both novices and experts. Based on these results,
      we formulated recommendations for the design of clinical information technology
      that would help to improve the acquisition of clinical information required by
      oral surgeons at all levels of expertise in their clinical decision-making. 

PMID- 26292580
TI  - Structural insights into the interactions of phorbol ester and bryostatin
      complexed with protein kinase C: a comparative molecular dynamics simulation
      study.
AB  - Protein kinase C (PKC) isozymes are important regulatory enzymes that have been
      implicated in many diseases, including cancer, Alzheimer's disease, and in the
      eradication of HIV/AIDS. Given their potential clinical ramifications, PKC
      modulators, e.g. phorbol esters and bryostatin, are also of great interest in the
      drug development. However, structural details on the binding between PKC and its
      modulators, especially bryostatin - the highly potent and non-tumor promoting
      activator for PKCs, are still lacking. Here, we report the first comparative
      molecular dynamics study aimed at gaining structural insight into the mechanisms
      by which the PKC delta cys2 activator domain is used in its binding to phorbol
      ester and bryostatin-1. As anticipated in the phorbol ester binding, hydrogen
      bonds are formed through the backbone atoms of Thr242, Leu251, and Gly253 of PKC.
      However, the opposition of H-bond formation between Thr242 and Gly253 may cause
      the phorbol ester complex to become less stable when compared with the bryostatin
      binding. For the PKC delta-bryostatin complex, hydrogen bonds are formed between
      the Gly253 backbone carbonyl and the C30 carbomethoxy substituent of the ligand.
      Additionally, the indole Nepsilon1 of the highly homologous Trp252 also forms an
      H-bond to the C20 ester group on bryostatin. Backbone fluctuations also suggest
      that this latter H-bond formation may abrogate the transient interaction between
      Trp252 and His269, thus dampening the fluctuations observed on the nearby Zn(2+)
      coordinating residues. This new dynamic fluctuation dampening model can
      potentially benefit future design of new PKC modulators. 

PMID- 26292581
TI  - Noninvasive Discrimination of Coronary Chronic Total Occlusion and Subtotal
      Occlusion by Coronary Computed Tomography Angiography.
AB  - OBJECTIVES: The aim of this study was to investigate whether noninvasive
      discrimination of chronic total occlusion (CTO), a complete interruption of
      coronary artery flow, and subtotal occlusion (STO), a functional total occlusion,
      is feasible using coronary computed tomography angiography (CTA). BACKGROUND: CTO
      and STO may be different in pathophysiology and clinical treatment strategy.
      METHODS: We included 486 consecutive patients (median age 63 years, 82% male) who
      showed a total of 553 completely occluded coronary arteries in coronary CTA. The
      length of occlusion, side branches, shape of proximal stump, and collateral
      vessels were measured as anatomical findings. Transluminal attenuation gradient,
      which reflects intraluminal contrast kinetics and functional extent of collateral
      flow, was measured as a physiological surrogate. All patients were followed by
      invasive coronary angiography. RESULTS: Coronary arteries with CTO showed longer
      occlusion length (cutoff >= 15 mm), higher distal transluminal attenuation
      gradient (cutoff >=-0.9 Hounsfield units [HU]/10 mm), more frequent side
      branches, blunted stump, cross-sectional calcification >= 50%, and collateral
      vessels compared with arteries with STO (p < 0.001, all). The combination of
      these findings could distinguish CTO from STO (c-statistics = 0.88 [95%
      confidence interval: 0.94 to 0.90], sensitivity 83%, specificity 77%, positive
      predictive value 55%, negative predictive value 93%; p < 0.001). Percutaneous
      coronary intervention (PCI) was attempted in 342 arteries and was successful in
      279 arteries (82%). The computed tomography findings could predict the
      unsuccessful PCI (c-statistics = 0.70 [95% confidence interval: 0.65 to 0.75],
      sensitivity 63%, specificity 73%, positive predictive value 91%, negative
      predictive value 31%; p < 0.001). CONCLUSIONS: Noninvasive coronary CTA could
      discern CTO from STO, and also could predict the success of attempted PCI.

PMID- 26292582
TI  - Discrimination of Coronary Subtotal Occlusion and Chronic Total Occlusion by
      Computed Tomographic Angiography.

PMID- 26292583
TI  - Invasive Cardiologists Are Exposed to Greater Left Sided Cranial Radiation: The
      BRAIN Study (Brain Radiation Exposure and Attenuation During Invasive Cardiology
      Procedures).
AB  - OBJECTIVES: This study sought to determine radiation exposure across the cranium
      of cardiologists and the protective ability of a nonlead, XPF (barium
      sulfate/bismuth oxide) layered cap (BLOXR, Salt Lake City, Utah) during
      fluoroscopically guided, invasive cardiovascular (CV) procedures. BACKGROUND:
      Cranial radiation exposure and potential for protection during contemporary
      invasive CV procedures is unclear. METHODS: Invasive cardiologists wore an XPF
      cap with radiation attenuation ability. Six dosimeters were fixed across the
      outside and inside of the cap (left, center, and right), and 3 dosimeters were
      placed outside the catheterization lab to measure ambient exposure. RESULTS:
      Seven cardiology fellows and 4 attending physicians (38.4 +/- 7.2 years of age;
      all male) performed diagnostic and interventional CV procedures (n = 66.2 +/- 27
      cases/operator; fluoroscopy time: 14.9 +/- 5.0 min). There was significantly
      greater total radiation exposure at the outside left and outside center (106.1 +/
      33.6 mrad and 83.1 +/- 18.9 mrad) versus outside right (50.2 +/- 16.2 mrad; p <
      0.001 for both) locations of the cranium. The XPF cap attenuated radiation
      exposure (42.3 +/- 3.5 mrad, 42.0 +/- 3.0 mrad, and 41.8 +/- 2.9 mrad at the
      inside left, inside center, and inside right locations, respectively) to a level
      slightly higher than that of the ambient control (38.3 +/- 1.2 mrad, p = 0.046).
      After subtracting ambient radiation, exposure at the outside left was 16 times
      higher than the inside left (p < 0.001) and 4.7 times higher than the outside
      right (p < 0.001). Exposure at the outside center location was 11 times higher
      than the inside center (p < 0.001), whereas no difference was observed on the
      right side. CONCLUSIONS: Radiation exposure to invasive cardiologists is
      significantly higher on the left and center compared with the right side of the
      cranium. Exposure may be reduced similar to an ambient control level by wearing a
      nonlead XPF cap. (Brain Radiation Exposure and Attenuation During Invasive
      Cardiology Procedures [BRAIN]; NCT01910272).

PMID- 26292586
TI  - A Prospective, Multicenter Study of a Novel Mesh-Covered Carotid Stent: The
      CGuard CARENET Trial (Carotid Embolic Protection Using MicroNet).
AB  - OBJECTIVES: This study sought to evaluate the feasibility of the CGuard Carotid
      Embolic Protective Stent system-a novel thin strut nitinol stent combined with a
      polyethylene terephthalate mesh covering designed to prevent embolic events from
      the target lesion in the treatment of carotid artery lesions in consecutive
      patients suitable for carotid artery stenting. BACKGROUND: The risk of cerebral
      embolization persists throughout the carotid artery stenting procedure and
      remains during the stent healing period. METHODS: A total of 30 consecutive
      patients (age 71.6 +/- 7.6 years, 63% male) meeting the conventional carotid
      artery stenting inclusion criteria were enrolled in 4 centers in Germany and
      Poland. RESULTS: The primary combined endpoint was the procedure success of the
      CGuard system and the number and volume of new lesions on the ipsilateral side
      assessed by diffusion-weighted magnetic resonance imaging at 48 h post-procedure
      and at 30 days. The secondary endpoint was 30-day major adverse cardiac or
      cerebrovascular events (death, stroke, or myocardial infarction). Protection
      devices were used in all procedures. Procedure success was 100%, with 0%
      procedural complications. The 30-day major adverse cardiac or cerebrovascular
      events rate was 0%. New ipsilateral ischemic lesions at 48 h occurred in 37.0% of
      patients and the average lesion volume was 0.039 +/- 0.08 cm(3). The 30-day
      diffusion-weighted magnetic resonance imaging showed complete resolution of all
      but 1 periprocedural lesion and only 1 new minor (0.116 cm(3)) lesion in relation
      to the 48-h scan. CONCLUSIONS: The use of the CGuard system in patients
      undergoing carotid artery stenting is feasible. In addition, the benefit of using
      CGuard may extend throughout the stent healing period.

PMID- 26292584
TI  - Health Status After Transcatheter or Surgical Aortic Valve Replacement in
      Patients With Severe Aortic Stenosis at Increased Surgical Risk: Results From the
      CoreValve US Pivotal Trial.
AB  - OBJECTIVES: This study sought to compare the health status outcomes for patients
      treated with either self-expanding transcatheter aortic valve replacement (TAVR)
      or surgical aortic valve replacement (AVR). BACKGROUND: In patients at increased
      surgical risk, TAVR with a self-expanding bioprosthesis is associated with
      improved 1-year survival compared with AVR. However, elderly patients may be just
      as concerned with quality-of-life improvement as with prolonged survival as a
      goal of treatment. METHODS: Between 2011 and 2012, 795 patients with severe
      aortic stenosis at increased surgical risk were randomized to TAVR or AVR in the
      CoreValve US Pivotal Trial. Health status was assessed at baseline, 1 month, 6
      months, and 1 year using the Kansas City Cardiomyopathy Questionnaire, Medical
      Outcomes Study Short-Form 12 Questionnaire, and EuroQOL 5-dimension
      questionnaire; growth curve models were used to examine changes over time.
      RESULTS: Over the 1-year follow-up period, disease-specific and generic health
      status improved substantially for both treatment groups. At 1 month, there was a
      significant interaction between the benefit of TAVR over AVR and access site.
      Among surviving patients eligible for iliofemoral (IF) access, there was a
      clinically relevant early benefit with TAVR across all disease-specific and
      generic health status measures. Among the non-IF cohort, however, most health
      status measures were similar for TAVR and AVR, although there was a trend toward
      early benefit with TAVR on the Short-Form 12 Questionnaire's physical health
      scale. There were no consistent differences in health status between TAVR and AVR
      at the later time points. CONCLUSIONS: Health status improved substantially in
      surviving patients with increased surgical risk who were treated with either self
      expanding TAVR or AVR. TAVR via the IF route was associated with better early
      health status compared with AVR, but there was no early health status benefit
      with non-IF TAVR compared with AVR. (Safety and Efficacy Study of the Medtronic
      CoreValve(r) System in the Treatment of Symptomatic Severe Aortic Stenosis in
      High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement;
      NCT01240902).

PMID- 26292587
TI  - Cerebral Embolization: The Cost of Doing Invasive Business.

PMID- 26292585
TI  - Inverse Relationship Between Membranous Septal Length and the Risk of
      Atrioventricular Block in Patients Undergoing Transcatheter Aortic Valve
      Implantation.
AB  - OBJECTIVES: This study sought to examine whether imaging of the atrioventricular
      (AV) membranous septum (MS) by computed tomography (CT) can be used to identify
      patient-specific anatomic risk of high-degree AV block and permanent pacemaker
      (PPM) implantation before transcatheter aortic valve implantation (TAVI) with
      self-expandable valves. BACKGROUND: MS length represents an anatomic surrogate of
      the distance between the aortic annulus and the bundle of His and may therefore
      be inversely related to the risk of conduction system abnormalities after TAVI.
      METHODS: Seventy-three consecutive patients with severe aortic stenosis underwent
      contrast-enhanced CT before TAVI. The aortic annulus, aortic valve, and AV
      junction were assessed, and MS length was measured in the coronal view. RESULTS:
      In 13 patients (18%), high-degree AV block developed, and 21 patients (29%)
      received a PPM. Multivariable logistic regression analysis revealed MS length as
      the most powerful pre-procedural independent predictor of high-degree AV block
      (odds ratio [OR]: 1.35, 95% confidence interval [CI]: 1.1 to 1.7, p = 0.01) and
      PPM implantation (OR: 1.43, 95% CI: 1.1 to 1.8, p = 0.002). When taking into
      account pre- and post-procedural parameters, the difference between MS length and
      implantation depth emerged as the most powerful independent predictor of high
      degree AV block (OR: 1.4, 95% CI: 1.2 to 1.7, p < 0.001), whereas the difference
      between MS length and implantation depth and calcification in the basal septum
      were the most powerful independent predictors of PPM implantation (OR: 1.39, 95%
      CI: 1.2 to 1.7, p < 0.001 and OR: 4.9, 95% CI: 1.2 to 20.5, p = 0.03;
      respectively). CONCLUSIONS: Short MS, insufficient difference between MS length
      and implantation depth, and the presence of calcification in the basal septum,
      factors that may all facilitate mechanical compression of the conduction tissue
      by the implanted valve, predict conduction abnormalities after TAVI with self
      expandable valves. CT assessment of membranous septal anatomy provides unique pre
      procedural information about the patient-specific propensity for the risk of AV
      block.

PMID- 26292588
TI  - The Effect of Post-Exercise Ankle-Brachial Index on Lower Extremity
      Revascularization.
AB  - OBJECTIVES: The purpose of this study was to investigate the effect of post
      exercise ankle-brachial index (ABI) on the incidence of lower extremity (LE)
      revascularization, cardiovascular outcomes, and all-cause mortality in patients
      with normal and abnormal resting ABI. BACKGROUND: The clinical and prognostic
      value of post-exercise ABI in the setting of normal or abnormal resting ABI
      remains uncertain. METHODS: A total of 2,791 consecutive patients with ABI
      testing between September 2005 and January 2010 were classified into group 1:
      normal resting (NR)/normal post-exercise (NE); group 2: NR/abnormal post-exercise
      (AE); group 3: abnormal resting (AR)/NE; and group 4: AR/AE. Abnormal post
      exercise ABI was defined as a drop of >20% from resting ABI as per the American
      College of Cardiology/American Heart Association guidelines. The primary endpoint
      was incidence of LE revascularization. Secondary endpoints were major adverse
      cardiovascular events (MACE) and all-cause mortality. Associations between post
      exercise ABI and outcomes were adjusted using multivariable Cox proportional
      hazard and propensity analyses. RESULTS: Compared with group 1 (NR/NE), group 2
      (NR/AE) had increased LE revascularization (propensity-matched adjusted hazard
      ratio [HR]: 6.63, 95% confidence interval [CI]: 3.13 to 14.04; p < 0.001) but no
      differences in MACE or all-cause mortality. When resting ABI was abnormal, group
      4 (AR/AE) compared with group 3 (AR/NE), abnormal post-exercise ABI was still
      associated with increased LE revascularization (adjusted HR: 1.59, 95% CI: 1.11
      to 2.28; p = 0.01), which persisted after propensity matching (adjusted HR: 2.32,
      95% CI: 1.52 to 3.54; p < 0.001). Compared with group 1 (NR/NE) and after
      propensity matching, group 4 (AR/AE) had a significant increase in MACE (adjusted
      HR: 1.44, 95% CI: 1.09 to 1.90; p = 0.009) and a trend toward increased all-cause
      mortality (adjusted HR: 1.37, 95% CI: 0.99 to 1.88; p = 0.052); however, group 3
      (AR/NE) did not. CONCLUSIONS: Post-exercise ABI appears to offer both clinical
      (lower extremity revascularization) and prognostic information in those with
      normal and abnormal resting ABI.

PMID- 26292589
TI  - The Exercise Ankle-Brachial Index: A Leap Forward in Noninvasive Diagnosis and
      Prognosis.

PMID- 26292590
TI  - Acute Thrombogenicity of a Durable Polymer Everolimus-Eluting Stent Relative to
      Contemporary Drug-Eluting Stents With Biodegradable Polymer Coatings Assessed Ex
      Vivo in a Swine Shunt Model.
AB  - OBJECTIVES: This study sought to evaluate whether the permanent fluoropolymer
      coated Xience Xpedition everolimus-eluting stent (Xience-EES) exhibits lower
      acute thrombogenicity compared with contemporary drug-eluting stents (DES) with
      biodegradable polymer coatings in an acute swine shunt model. BACKGROUND:
      Previous pre-clinical and clinical experience suggests that several factors may
      influence the predisposition for acute thrombus formation of polymer-coated DES,
      including stent design and the polymer coating technology. It remains unclear
      whether relevant differences exist with respect to acute thrombogenicity,
      particularly between current commercial stent designs using permanent polymers
      and those using biodegradable polymers. METHODS: An ex vivo carotid to jugular
      arteriovenous porcine shunt model involving a test circuit of 3 in-line stents,
      was used to test acute thrombogenicity, where Xience-EES (n = 24) was compared
      with 4 CE-marked DES with biodegradable polymer coatings (BioMatrix Flex,
      Synergy, Nobori, and Orsiro [n = 6 each]). After 1 h of circulation, platelet
      aggregation in whole mount stents was evaluated by confocal microscopy with
      immunofluorescent staining against dual platelet markers (CD61/CD42b) along with
      scanning electron microscopy. RESULTS: Xience-EES showed the least percentage of
      thrombus-occupied area as compared with the biodegradable polymer-coated DES,
      with a significant difference compared with BioMatrix Flex and Synergy (mean
      differences: [BioMatrix Flex: 15.54, 95% confidence interval [CI]: 11.34 to
      19.75, p < 0.001; Synergy: 8.64, 95% CI: 4.43 to 12.84, p < 0.001; Nobori: 4.22,
      95% CI: -0.06 to 8.49, p = 0.055; Orsiro: 2.95, 95% CI: -1.26 to 7.15, p =
      0.286). The number of cell nuclei on strut surfaces was also the least in Xience
      EES, with a significant difference relative to BioMatrix Flex, Nobori, and Orsiro
      (mean ratios: BioMatrix Flex: 4.73, 95% CI: 2.46 to 9.08, p < 0.001; Synergy:
      1.44, 95% CI: 0.75 to 2.76, p = 0.51; Nobori: 5.97, 95% CI: 3.11 to 11.44, p <
      0.001; Orsiro: 5.16, 95% CI: 2.69 to 9.91, p < 0.001). CONCLUSIONS: Xience-EES's
      overall design confers acute thromboresistance relative to contemporary DES with
      biodegradable coatings, with less platelet aggregation versus BioMatrix Flex and
      Synergy, and less inflammatory cell attachment versus BioMatrix Flex, Nobori, and
      Orsiro, in an ex vivo swine shunt model, which lends support to reported clinical
      findings of lower early stent thrombosis.

PMID- 26292592
TI  - Recurrent Neoatherosclerosis After Bioresorbable Vascular Scaffold Treatment of
      In-Stent Restenosis.

PMID- 26292591
TI  - Stroke With Valve Tissue Embolization During Transcatheter Aortic Valve
      Replacement Treated With Endovascular Intervention.

PMID- 26292593
TI  - Reply: von Willebrand Disease After TAVR: The Missing Link?

PMID- 26292594
TI  - von Willebrand Disease After TAVR: The Missing Link?

PMID- 26292595
TI  - Quantitative Evaluation of Residual Atrial Septal Defect Following Transseptal
      Catheterization for Intracardiac Interventional Procedures.

PMID- 26292596
TI  - Reply: Quantitative Evaluation of Residual Atrial Septal Defect Following
      Transseptal Catheterization for Intracardiac Interventional Procedures.

PMID- 26292597
TI  - Iatrogenic Atrial Septal Defect After MitraClip Therapy.

PMID- 26292598
TI  - Reply: Iatrogenic Atrial Septal Defect After MitraClip Therapy.

PMID- 26292599
TI  - True Fractional Flow Reserve of Left Main Coronary Artery Stenosis in the
      Presence of Downstream Coronary Stenoses.

PMID- 26292600
TI  - Reply: True Fractional Flow Reserve of Left Main Coronary Artery Stenosis in the
      Presence of Downstream Coronary Stenoses.

PMID- 26292601
TI  - The Role of Drug-Eluting Balloons in Bifurcations: The Remaining Variable to Fit
      the Perfect Equation.

PMID- 26292602
TI  - Reply: The Role of Drug-Eluting Balloons in Bifurcations: The Remaining Variable
      to Fit the Perfect Equation.

PMID- 26292603
TI  - Radial Artery in Breast Cancer Survivors: A Possible Choice but Always With
      Caution.

PMID- 26292604
TI  - Do You Fear the First of July?

PMID- 26292605
TI  - Percutaneous Luminal Reconstruction of Giant Saphenous Vein Graft Aneurysm.

PMID- 26292606
TI  - An Unusual Complication After Bioresorbable Scaffold Implantation: Visualization
      of Intramural Hematoma by Optical Coherence Tomography.

PMID- 26292607
TI  - Very Late Thrombosis of a Transcatheter Aortic Valve-in-Valve.

PMID- 26292608
TI  - Performance of Tsol-p27 antigen for the serological diagnosis of cysticercosis in
      Mozambique.
AB  - The diagnosis of neurocysticercosis (NCC) requires expensive neuroimaging
      techniques that are seldom affordable for people in endemic countries.
      Accordingly, there is a need for new low-cost diagnostic methods that offer high
      sensitivity and specificity. In this study, we evaluated Western blot analysis of
      the previously described recombinant antigen Tsol-p27 in relation to a commercial
      or in-house enzyme-linked immunosorbent assay (ELISA) for NCC, and compared the
      results with those provided by a commercial enzyme-linked immunoelectrotransfer
      blot (EITB) assay, which was regarded as the reference standard method. The
      analysed serum samples were obtained from 165 people, 18 of whom were confirmed
      to be NCC positive by EITB. Comparing our Western blot analysis of Tsol-p27 with
      a previous evaluation performed in Central America showed similar specificity
      (96.69% versus 97.8%) and sensitivity (85.71% versus 86.7%). The present results
      indicate that the recombinant Tsol-p27 antigen provides good sensitivity and
      specificity, and might be preferable as a diagnostic antigen in poorly equipped
      laboratories in endemic countries. 

PMID- 26292610
TI  - Erratum: High-frame rate four dimensional optoacoustic tomography enables
      visualization of cardiovascular dynamics and mouse heart perfusion.

PMID- 26292609
TI  - The effect of ankle bracing on lower extremity biomechanics during landing: A
      systematic review.
AB  - OBJECTIVES: To examine the evidence for effect of ankle bracing on lower
      extremity landing biomechanics. DESIGN: Literature review. METHODS: Systematic
      search of the literature on EBSCO health databases. Articles critiqued by two
      reviewers. RESULTS: Ten studies were identified which investigated the effect of
      ankle bracing on landing biomechanics. Overall results suggest that landing
      biomechanics are altered with some brace types but studies disagree as to the
      particular variables affected. CONCLUSIONS: There is evidence that ankle bracing
      may alter lower-extremity landing biomechanics in a manner which predisposes
      athletes to injury. The focus of studies on specific biomechanical variables
      rather than biomechanical patterns, analysis of pooled data means in the presence
      of differing landing styles between participants, variation in landing-tasks
      investigated in different studies, and lack of studies investigating goal
      directed sport-specific landing tasks creates difficulty in interpreting results.
      These areas require further research.

PMID- 26292611
TI  - Redefining clinical risk classification in children with precursor B cell acute
      lymphoblastic leukemia using pre-treatment absolute lymphocyte count.

PMID- 26292612
TI  - Editorial Comment.

PMID- 26292613
TI  - Reply: To PMID 26184880.

PMID- 26292614
TI  - Editorial Comment.

PMID- 26292615
TI  - Biliary complications of arterial chemoembolization of hepatocellular carcinoma.
AB  - RATIONALE AND BACKGROUND: Transarterial chemoembolization (TACE) is the most
      frequently used palliative therapy for unresectable hepatocellular carcinoma
      (HCC). It is a safe and effective procedure with few major and minor
      complications. Rarely, biliary complications are also encountered following TACE.
      The goal of our study was to investigate the incidence and the presentation of
      biliary complications following TACE in patients with HCC. MATERIAL AND METHODS:
      In this retrospective study, data of patients with HCC who underwent TACE between
      June 2002 to December 2014 were obtained from the records. Their detailed
      information about the procedure of TACE, diagnosis of biliary complications and
      subsequent management details were reviewed. RESULT: One hundred and sixty-eight
      patients with HCC underwent 305 procedures of TACE. Of these, biliary
      complications of various severities developed in 6 (3.6%) patients leading to an
      incidence of 1.9% (6/305). Minimal intrahepatic biliary dilatation (IHBD)
      occurred in three, biliary stricture in one and intrahepatic biloma in two
      patients. Supportive management was undertaken for IHBD patients while
      percutaneous aspiration and naso-biliary drainage was performed for the infected
      bilomas. CONCLUSION: Biliary complications following TACE are infrequent.
      Diagnosis should be suspected clinically and confirmed with imaging. Treatment
      depends on the severity. Enforcing specific measures can minimize its frequency.

PMID- 26292616
TI  - Arterial splanchnic aneurysms: Presentation, treatment and outcome in 112
      patients.
AB  - PURPOSE: The purpose of this study was to identify subgroups with different risks
      of progression and their appropriate management among the heterogeneous group of
      112 patients diagnosed with splanchnic aneurysm. METHODS: Using radiology
      databases and medical records of our institution (Hospital Edouard-Herriot, Lyon,
      France), we undertook a retrospective review of all patients diagnosed with
      splanchnic artery aneurysms from 1995 to 2011. Cases were analyzed by aneurysm
      location, etiology and a distinction was also made between true and false
      aneurysms. RESULTS: False aneurysms were more likely than true aneurysms to be
      diagnosed as symptomatic and/or ruptured (TA: 50/66 patients asymptomatic vs. FA:
      16/46 asymptomatic, P<0.05) with a rupture rate of 59% (27/46) which was
      unrelated to the size of aneurysms. Percutaneous treatment was carried in the
      majority of patients with a final success rate of 91%. Peripancreatic true
      aneurysms were associated in 75% of cases with celiac occlusive disease and
      diagnosed mostly in symptomatic patients (7/9: 78%) with a rupture rate of 44%
      unrelated to their size. Radiologic treatment has faced problems due to failure
      of catheterization and incomplete embolization, although there have been cases in
      which delayed occlusion was achieved. Common true aneurysms were incidental
      findings in 87% (57/66) of patients with 3 ruptured aneurysms which were larger
      than 2 cm. Observation in that group was safe: significant growth was seen only
      in one patient and the embolization required was successful. Splanchnic false
      aneurysms and peripancreatic true aneurysms carried a high and an unpredictable
      risk of rupture that warranted prompt endovascular treatment as soon as possible.
      CONCLUSIONS: Stratification by localization and by the true or false appearance
      of the aneurysm was an effective (means of identifying) way to identify subgroups
      with different risks of progression. False aneurysms and peripancreatic true
      aneurysms carried a high and unpredictable risk of rupture. The splanchnic
      aneurysms should have been treated in the case of patients of childbearing age,
      size >= 20 mm, and in the case of liver transplantation. Other splanchnic
      aneurysms should either have been observed, if smaller than 2 cm. In the absence
      of rigorous published comparisons, surgical and endovascular methods should have
      been considered equally suitable in the elective treatment of these patients.

PMID- 26292617
TI  - Supramolecular hydrogels constructed by red-light-responsive host-guest
      interactions for photo-controlled protein release in deep tissue.
AB  - We report a novel red-light-responsive supramolecule. The tetra-ortho-methoxy
      substituted azobenzene (mAzo) and beta-cyclodextrin (beta-CD) spontaneously
      formed a supramolecular complex. The substituted methoxy groups shifted the
      responsive wavelength of the azo group to the red light region, which is in the
      therapeutic window and desirable for biomedical applications. Red light induced
      the isomerization of mAzo and the disassembly of the mAzo/beta-CD supramolecular
      complex. We synthesized a mAzo-functionalized polymer and a beta-CD
      functionalized polymer. Mixing the two polymers in an aqueous solution generated
      a supramolecular hydrogel. Red light irradiation induced a gel-to-sol transition
      as a result of the disassembly of the mAzo/beta-CD complexes. Proteins were
      loaded in the hydrogel. Red light could control protein release from the hydrogel
      in tissue due to its deep penetration depth in tissue. We envision the use of red
      light-responsive supramolecules for deep-tissue biomedical applications. 

PMID- 26292618
TI  - Population difference in the association of BDNF promoter methylation with mild
      cognitive impairment in the Xinjiang Uygur and Han populations.
AB  - BACKGROUND: Mild cognitive impairment (MCI) is a clinical transitional stage
      between normal aging and Alzheimer disease, which leads to memory loss and a
      reduction in cognitive function. Brain derived neurotrophic factor (BDNF) plays
      an important role in neuronal development and plasticity. The aim of this study
      was to explore the association between BDNF promoter methylation and MCI in the
      Xinjiang Uygur and Han populations. METHODS: A DNA methylation assay using
      bisulfite pyrosequencing technology was performed on 96 Uygur and 96 Han Chinese
      individuals from Xinjiang province, China. RESULTS: We found a significantly
      higher BDNF methylation level in Han MCI cases than in Uygur MCI cases in males
      from Xinjiang province (p=0.022). In addition, the methylation level was
      significantly higher in Xinjiang Han healthy Chinese individuals (Northwestern
      China) than in Ningbo Han healthy Chinese individuals (Southeastern China)
      (Female and Male: p=1.17E-05; Female: p=0.020; Male: p=1.37E-04). But our results
      showed no significant association of BDNF methylation with MCI in either the
      Uygur or Han Chinese populations (p>0.05). Further gender-based subgroup analyses
      did not find any significant results (p>0.05). CONCLUSION: Our results indicate
      that different levels of BDNF methylation may be present in different populations
      and environments. This study also provides further information regarding the
      relationship between BDNF methylation levels and MCI in Xinjiang Uygur and Han
      ethnic groups.

PMID- 26292619
TI  - Obsessive-compulsive disorders and anxiety disorders: A comparison of personality
      and emotionality patterns.
AB  - Even though obsessive-compulsive disorders (OCD) and anxiety disorders (AD) have
      been separated in the taxonomy adopted by the fifth edition of the Diagnostic and
      Statistical Manual of Mental Disorders, many issues remain concerning the
      physiopathological similarities and differences between those categories. Our
      objective was therefore to explore and compare their personality and emotional
      features, with the assumption that the distinction of two independent spectrums
      should imply the existence of two partially distinct temperamental profiles. We
      used the Temperament and Character Inventory (TCI-R) and the Positive and
      Negative Emotionality (PNE) scale to compare two groups of patients with OCD
      (n=227) or AD (n=827). The latter group included patients with social anxiety
      disorder, panic disorder, agoraphobia, and generalized anxiety disorder. Most
      temperament, character and emotionality measures showed no significant
      differences between both groups. In the personality measures results, only the
      self-directedness score (TCI-R) was significantly lower in OCD patients but this
      difference was not significant when the comparison was adjusted for the
      depressive scale score and age. Only lower PNE positive affects scores were
      obtained in OCD patients in the adjusted comparisons. These findings suggest that
      OCD and AD are not really distinguishable from the point of view of associated
      personality traits. 

PMID- 26292620
TI  - High estradiol levels improve false memory rates and meta-memory in highly
      schizotypal women.
AB  - Overconfidence in false memories is often found in patients with schizophrenia
      and healthy participants with high levels of schizotypy, indicating an impairment
      of meta-cognition within the memory domain. In general, cognitive control is
      suggested to be modulated by natural fluctuations in oestrogen. However, whether
      oestrogen exerts beneficial effects on meta-memory has not yet been investigated.
      The present study sought to provide evidence that high levels of schizotypy are
      associated with increased false memory rates and overconfidence in false
      memories, and that these processes may be modulated by natural differences in
      estradiol levels. Using the Deese-Roediger-McDermott paradigm, it was found that
      highly schizotypal participants with high estradiol produced significantly fewer
      false memories than those with low estradiol. No such difference was found within
      the low schizotypy participants. Highly schizotypal participants with high
      estradiol were also less confident in their false memories than those with low
      estradiol; low schizotypy participants with high estradiol were more confident.
      However, these differences only approached significance. These findings suggest
      that the beneficial effect of estradiol on memory and meta-memory observed in
      healthy participants is specific to highly schizotypal individuals and might be
      related to individual differences in baseline dopaminergic activity. 

PMID- 26292622
TI  - Oat beta-glucan ameliorates dextran sulfate sodium (DSS)-induced ulcerative
      colitis in mice.
AB  - Ulcerative colitis is a major inflammatory bowel disease (IBD), characterized by
      inflammation within the gastrointestinal tract through chronic or relapsing
      immune system activation. The aim of this study is to investigate the potential
      protective effect of oat beta-glucan (betaG) against colitis induced by DSS in
      mice. Eighty mice were randomly divided into the control group (no DSS, no
      betaG), DSS group (DSS only), DSS + L-betaG group (DSS plus 500 mg per kg betaG),
      and DSS + H-betaG group (DSS plus 1000 mg per kg betaG). Compared with the DSS
      group, administration of betaG significantly reduced clinical symptoms with less
      weight loss, diarrhea and shortening of the colon, the severity of colitis was
      significantly inhibited as evidenced by the reduced disease activity index (DAI)
      and degree of histological damage in colon. Moreover, treatment with betaG not
      only decreased myeloperoxidase activity (MPO), and nitric oxide (NO) and
      malondialdehyde (MDA) levels, but also inhibited mRNA and protein expression of
      pro-inflammatory factors such as TNF-alpha, IL-1beta, IL-6 and iNOS. This
      suggests that oat betaG in diet might exhibit an anti-inflammatory function
      against colitis through inhibition of expression of pro-inflammatory factors. 

PMID- 26292621
TI  - Functional autoantibodies in systemic sclerosis.
AB  - Functional autoantibodies are an emerging field of research that focuses on the
      effects of these immunoglobulins when they bind to their target molecules.
      Accumulating information now exists about the molecular targets and precise
      binding mechanisms of functional autoantibodies as well as about their downstream
      effects. These data raise the need to distinguish functional autoantibodies from
      non-functional autoantibodies with regard to their ability to stimulate or to
      inhibit their target protein via binding. The presence of autoantibodies has been
      documented in autoimmune disorders decades ago, but meanwhile, more and more
      autoantibodies have been identified as functional, acting as pathogenic drivers
      involved in the induction of organ-specific damage in systemic sclerosis as well
      as in other autoimmune disorders. These findings offer new opportunities for the
      development of novel therapeutic strategies. 

PMID- 26292623
TI  - Association of APE1 Gene Asp148Glu Variant with Digestive Cancer: A Meta
      Analysis.
AB  - BACKGROUND: Apurinic/apyrimidinic endonuclease-1 (APE1) is a rate-limiting enzyme
      in DNA base excision repair and has been implicated in carcinogenesis. In this
      study, we summarize available data to examine the susceptibility of APE1 gene
      Asp148Glu variant to digestive cancer via a meta-analysis. MATERIAL AND METHODS:
      Study selection and data abstraction were conducted independently by 2 authors.
      Random-effects model was utilized to pool effect estimates. Heterogeneity and
      publication bias were addressed. RESULTS: Sixteen articles involving 4916
      digestive cancer patients and 7748 controls were qualified for this meta
      analysis. Overall association showed an indicative association between Asp148Glu
      variant and digestive cancer under allelic (odds ratio or OR=1.11; 95% confidence
      interval or CI: 0.99-1.25; P=0.074) and dominant (OR=1.18; 95% CI: 1.00-1.40;
      P=0.056) models, with strong evidence of heterogeneity. Deviation from Hardy
      Weinberg equilibrium was an obvious source of heterogeneity. In subgroup analyses
      by cancer sites, this variant was significantly associated with the increased
      risk for hepatocellular cancer under allelic (OR=1.50; 95% CI: 1.25-1.80;
      P<0.001) and homozygous genotypic (OR=1.55; 95% CI: 1.02-2.29; P=0.028) models.
      There were low probabilities of publication bias for the above comparisons.
      CONCLUSIONS: The results of this meta-analysis collectively suggest that APE1
      gene Asp148Glu variant is not a risk-conferring factor for digestive cancer.
      Further large and well-designed studies are required.

PMID- 26292624
TI  - Calculation of retention time tolerance windows with absolute confidence from
      shared liquid chromatographic retention data.
AB  - Compound identification by liquid chromatography-mass spectrometry (LC-MS) is a
      tedious process, mainly because authentic standards must be run on a user's
      system to be able to confidently reject a potential identity from its retention
      time and mass spectral properties. Instead, it would be preferable to use shared
      retention time/index data to narrow down the identity, but shared data cannot be
      used to reject candidates with an absolute level of confidence because the data
      are strongly affected by differences between HPLC systems and experimental
      conditions. However, a technique called "retention projection" was recently shown
      to account for many of the differences. In this manuscript, we discuss an
      approach to calculate appropriate retention time tolerance windows for projected
      retention times, potentially making it possible to exclude candidates with an
      absolute level of confidence, without needing to have authentic standards of each
      candidate on hand. In a range of multi-segment gradients and flow rates run among
      seven different labs, the new approach calculated tolerance windows that were
      significantly more appropriate for each retention projection than global
      tolerance windows calculated for retention projections or linear retention
      indices. Though there were still some small differences between the labs that
      evidently were not taken into account, the calculated tolerance windows only
      needed to be relaxed by 50% to make them appropriate for all labs. Even then, 42%
      of the tolerance windows calculated in this study without standards were narrower
      than those required by WADA for positive identification, where standards must be
      run contemporaneously. 

PMID- 26292626
TI  - The effect of geometrical presentation of multimodal cation-exchange ligands on
      selective recognition of hydrophobic regions on protein surfaces.
AB  - The effects of spatial organization of hydrophobic and charged moieties on
      multimodal (MM) cation-exchange ligands were examined by studying protein
      retention behavior on two commercial chromatographic media, CaptoTM MMC and
      NuviaTM cPrimeTM. Proteins with extended regions of surface-exposed aliphatic
      residues were found to have enhanced retention on the Capto MMC system as
      compared to the Nuvia cPrime resin. The results further indicated that while the
      Nuvia cPrime ligand had a strong preference for interactions with aromatic
      groups, the Capto MMC ligand appeared to interact with both aliphatic and
      aromatic clusters on the protein surfaces. These observations were formalized
      into a new set of protein surface property descriptors, which quantified the
      local distribution of electrostatic and hydrophobic potentials as well as
      distinguishing between aromatic and aliphatic properties. Using these
      descriptors, high-performing quantitative structure-activity relationship (QSAR)
      models (R(2)>0.88) were generated for both the Capto MMC and Nuvia cPrime
      datasets at pH 5 and pH 6. Descriptors of electrostatic properties were generally
      common across the four models; however both Capto MMC models included descriptors
      that quantified regions of aliphatic-based hydrophobicity in addition to aromatic
      descriptors. Retention was generally reduced by lowering the ligand densities on
      both MM resins. Notably, elution order was largely unaffected by the change in
      surface density, but smaller and more aliphatic proteins tended to be more
      affected by this drop in ligand density. This suggests that modulating the
      exposure, shape and density of the hydrophobic moieties in multimodal
      chromatographic systems can alter the preference for surface exposed aliphatic or
      aromatic residues, thus providing an additional dimension for modulating the
      selectivity of MM protein separation systems. 

PMID- 26292627
TI  - Appropriate models for novel osteoporosis drug discovery and future perspectives.
AB  - INTRODUCTION: Osteoporosis is a common skeletal disorder characterized by
      compromised bone strength and increased fracture risk. It is becoming a growing
      health-economic problem worldwide. Over the past two decades, there has been
      considerable progress in the availability of compounds with antiresorptive or
      anabolic activity on bone. However, existing therapeutic strategies still have
      limitations. AREAS COVERED: In this review, the authors summarize past and
      current approaches for the development of antiresorptive and anabolic agents for
      osteoporosis together with their mechanisms of action. They also provide
      discussion on the application of new technologies for novel osteoporosis drug
      discovery. EXPERT OPINION: Thanks to the recent advances in molecular biology
      over the past few years, novel therapeutic targets for antiresorptive or anabolic
      compounds have been discovered and several promising new drugs are in preclinical
      and clinical development. Despite these advances, the current understanding of
      the mechanisms regulating bone remodeling is far from complete, leaving
      significant drawbacks to the discovery and the clinical development of novel
      therapeutic agents. Hopefully, improvements in functional genomics and
      bioinformatics, along with new technological approaches such as RNA silencing,
      quantitative proteomics, metabolomics, and the use of mesenchymal stem cells,
      will address these issues and widen our options for treating several disorders of
      bone metabolism, including osteoporosis.

PMID- 26292625
TI  - Retention projection enables accurate calculation of liquid chromatographic
      retention times across labs and methods.
AB  - Identification of small molecules by liquid chromatography-mass spectrometry (LC
      MS) can be greatly improved if the chromatographic retention information is used
      along with mass spectral information to narrow down the lists of candidates.
      Linear retention indexing remains the standard for sharing retention data across
      labs, but it is unreliable because it cannot properly account for differences in
      the experimental conditions used by various labs, even when the differences are
      relatively small and unintentional. On the other hand, an approach called
      "retention projection" properly accounts for many intentional differences in
      experimental conditions, and when combined with a "back-calculation" methodology
      described recently, it also accounts for unintentional differences. In this
      study, the accuracy of this methodology is compared with linear retention
      indexing across eight different labs. When each lab ran a test mixture under a
      range of multi-segment gradients and flow rates they selected independently,
      retention projections averaged 22-fold more accurate for uncharged compounds
      because they properly accounted for these intentional differences, which were
      more pronounced in steep gradients. When each lab ran the test mixture under
      nominally the same conditions, which is the ideal situation to reproduce linear
      retention indices, retention projections still averaged 2-fold more accurate
      because they properly accounted for many unintentional differences between the LC
      systems. To the best of our knowledge, this is the most successful study to date
      aiming to calculate (or even just to reproduce) LC gradient retention across
      labs, and it is the only study in which retention was reliably calculated under
      various multi-segment gradients and flow rates chosen independently by labs. 

PMID- 26292628
TI  - One-pot synthesis of podophyllotoxin-thiourea congeners by employing NH2SO3H/NaI:
      Anticancer activity, DNA topoisomerase-II inhibition, and apoptosis inducing
      agents.
AB  - A facile one-pot method for the synthesis of novel podophyllotoxin-thiourea
      congeners has been developed by using NH2SO3H/NaI system. Interestingly, 4beta
      azido podophyllotoxin reduction with concomitant aryl isothiocyanates coupling
      under mild reaction conditions has been achieved. These compounds have been
      investigated for their in vitro cytotoxicity against A549, MDA MB-231, DU-145,
      LNCaP, and HGC-27 cancer cell lines. Some of the representative compounds have
      selectively exhibited cytotoxicity on DU-145 (human prostate cancer) cells and
      the most potent compound was 4a (IC50 of 0.50 +/- 0.03 MUM) with optimal safety
      therapeutic window (81.7 fold) on normal human prostate cell line (RWPE-1, IC50
      of 40.85 +/- 0.78). The flow-cytometric analysis of the compound 4a in prostate
      cancer cells indicated a strong G2/M-phase arrest and significant topoisomerase
      II inhibition activity. Furthermore, these compounds induce apoptosis as observed
      by Acridine Orange and Ethidium Bromide (AO/EB) staining and Annexin V binding
      assay. Molecular docking results of the title compounds with topoisomerase
      IIalpha were presented as theoretical support for the experimental data.

PMID- 26292629
TI  - A simple and efficient dispersion correction to the Hartree-Fock theory (2):
      Incorporation of a geometrical correction for the basis set superposition error.
AB  - One of the most challenging problems in computer-aided drug discovery is the
      accurate prediction of the binding energy between a ligand and a protein. For
      accurate estimation of net binding energy DeltaEbind in the framework of the
      Hartree-Fock (HF) theory, it is necessary to estimate two additional energy
      terms; the dispersion interaction energy (Edisp) and the basis set superposition
      error (BSSE). We previously reported a simple and efficient dispersion
      correction, Edisp, to the Hartree-Fock theory (HF-Dtq). In the present study, an
      approximation procedure for estimating BSSE proposed by Kruse and Grimme, a
      geometrical counterpoise correction (gCP), was incorporated into HF-Dtq (HF-Dtq
      gCP). The relative weights of the Edisp (Dtq) and BSSE (gCP) terms were
      determined to reproduce DeltaEbind calculated with CCSD(T)/CBS or /aug-cc-pVTZ
      (HF-Dtq-gCP (scaled)). The performance of HF-Dtq-gCP (scaled) was compared with
      that of B3LYP-D3(BJ)-bCP (dispersion corrected B3LYP with the Boys and Bernadi
      counterpoise correction (bCP)), by taking DeltaEbind (CCSD(T)-bCP) of small non
      covalent complexes as 'a golden standard'. As a critical test, HF-Dtq-gCP
      (scaled)/6-31G(d) and B3LYP-D3(BJ)-bCP/6-31G(d) were applied to the complex model
      for HIV-1 protease and its potent inhibitor, KNI-10033. The present results
      demonstrate that HF-Dtq-gCP (scaled) is a useful and powerful remedy for
      accurately and promptly predicting DeltaEbind between a ligand and a protein,
      albeit it is a simple correction procedure. 

PMID- 26292630
TI  - Lithium battery lodged in the oesophagus: A report of three paediatric cases.
AB  - BACKGROUND: Over the last years the ingestion of disk batteries has become
      frequent in children with serious consequences. The severity of injuries is
      related to the growing use of new lithium batteries that may cause catastrophic
      damages when lodged in the oesophagus. METHODS: The notes of three consecutive
      children with lithium batteries lodged in the oesophagus, admitted to our
      Institute from 2010 to 2014, were reviewed. Clinical presentation, management,
      and outcome were considered. RESULTS: The first child, a 22-month-old girl, died
      of a sudden exsanguination due to an aorto-oesophageal fistula. The second case,
      a 5-year-old boy, had an exploratory thoracotomy to exclude aortic lesion before
      battery removal, and a spontaneous oesophageal perforation. The third child, a 18
      month-old boy, fully recovered after suffering ulcerative oesophageal burns.
      CONCLUSION: Lithium battery lodged in the oesophagus is a paediatric emergency
      requiring a multidisciplinary approach that can be implemented in a tertiary
      children's hospital.

PMID- 26292631
TI  - Prevalence of dyslipidemia in Japanese patients with rheumatoid arthritis and
      effects of atorvastatin treatment.
AB  - Few studies have examined dyslipidemia in patients with rheumatoid arthritis
      (RA), especially in Japanese cohorts. The aims of this study were to investigate
      the lipid profiles of RA patients, to assess the relationships between lipid
      profiles and RA activity and treatment, and to elucidate the effects of HMG-CoA
      reductase inhibitors (statins) in Japanese patients with RA. A multicenter
      observational study was conducted in 488 patients with RA. Serum total
      cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C)
      and high-density lipoprotein cholesterol (HDL-C) levels, and RA activity as
      assessed by disease activity score 28 (DAS28), and treatment for RA were analyzed
      retrospectively. In statin-treated patients, drug efficacy was also analyzed. The
      prevalence of hyper LDL-C, hyper TG, and hypo HDL-C were 29.3, 24.2, and 10.2%,
      respectively, and the overall prevalence of dyslipidemia was 56.5%. The level of
      HDL-C was inversely correlated with DAS28. Patients treated with low-dose
      glucocorticoids showed significantly higher levels of HDL-C and lower TC/HDL-C
      ratios compared with patients not receiving glucocorticoid treatment. Conversely,
      patients treated with biologic agents showed significantly higher levels of LDL
      C, lower levels of HDL-C, and higher TC/HDL-C ratios. Atorvastatin significantly
      improved lipid profiles after a few months of treatment. The prevalence of
      dyslipidemia in Japanese patients with RA is higher than that in the non-RA
      population. Our result suggests that controlling RA disease activity might
      improve lipid profiles and eventually lower cardiovascular risk. Low-dose
      atorvastatin was effective for treatment of dyslipidemia in RA patients but had
      no apparent effect on RA disease activity.

PMID- 26292633
TI  - Occurrence of Sweet syndrome under anti-TNF.
AB  - We report the occurrence of Sweet's syndrome in a patient treated with adalimumab
      for Crohn's disease. The imputability of adalimumab is at issue. 

PMID- 26292632
TI  - Prevalence of hyperuricemia and its correlates in rural Northeast Chinese
      population: from lifestyle risk factors to metabolic comorbidities.
AB  - The increasing trend of hyperuricemia in urban areas of China has been noted in
      the past decade. However, the prevalence of hyperuricemia in rural China has not
      been extensively investigated. We aimed to estimate the prevalence and risk
      factors of hyperuricemia and the associated comorbidities in rural Northeast
      China. This survey was conducted from July 2012 to August 2013. In this study, a
      total of 11,576 residents from the rural Northeast China were randomly selected
      and examined. Hyperuricemia was defined as serum uric acid >=416 MUmol/l in men
      and >=357 MUmol/l in women. Data regarding the demographic and lifestyle
      characteristics and the blood biochemical indexes of these participants were
      collected by well-trained personnel. The prevalence of hyperuricemia was 10.9 %
      and was more prevalent in men than in women (15.0 vs. 7.3 %, P < 0.001).
      Multivariate logistic regression models revealed that besides age, hyperuricemia
      in men was associated with ethnic minority [OR (95 %): 0.683 (0.472,0.989)],
      physical activity [moderate, OR (95 %): 0.716 (0.596,0.859); high, OR (95 %):
      0.527 (0.354,0.786)], current smoking [OR(95 %):1.380 (1.179,1.616)], and current
      drinking [OR(95 %):0.705 (0.603,0.825)], while in women was only associated with
      ethnic minority [OR(95 %):0.485 (0.262,0.896)]. After adjusting for possible
      confounders, hyperuricemia was related to different subtypes of cardiometabolic
      comorbidities in both gender like abdominal obesity, general obesity,
      hypertriglyceridemia, hypertension, hypercholesterolemia, and low HDL-C. Besides,
      in women only, hyperuricemia was related to diabetes and high LDL-C.
      Hyperuricemia was common among residents living in rural Northeast China
      especially among men. Ethnic minority, physical activity, current smoking, and
      drinking contributed to hyperuricemia in this population. 

PMID- 26292634
TI  - Relationship between temperature and development of Galendromus flumenis (Acari:
      Phytoseiidae), a predator of Banks grass mite (Acari: Tetranychidae).
AB  - The Banks grass mite, Oligonychus pratensis (Banks) (Acari: Tetranychidae), is a
      serious pest of grains, grasses and dates. In order to develop and optimize
      biological control strategies against the Banks grass mite, the survival and
      development of the predator, Galendromus flumenis (Chant) (Acari: Phytoseiidae),
      at eleven constant temperatures between 12 and 44 degrees C were determined. The
      survival rates of G. flumenis (67.4-89.5 %) were highest between 26 and 38
      degrees C although it developed successfully from egg to adult at temperatures
      ranging from 18 to 42 degrees C. The lower temperature threshold (T 0 ) and
      thermal constant (K) for total immature development were 13.3 degrees C and 145.3
      degree-days, respectively. The upper temperature threshold was 44.3 degrees C,
      and the optimal temperature for development was calculated to be 37.5 degrees C.
      These results indicate that G. flumenis is better adapted to high temperatures
      than most predators in the Phytoseiidae. In addition, the thermal requirements
      for total development of G. flumenis was found to be very close to those of O.
      pratensis which indicates that there should be synchrony between the occurrence
      of the prey and the predator. Therefore, the lack of predation observed in the
      field is related to other factors, such as the developmental time between O.
      pratensis and G. flumenis, or the inability of the predator to establish at the
      same time, and in the same location, as the prey.

PMID- 26292635
TI  - Energy dissipative photoprotective mechanism of carotenoid spheroidene from the
      photoreaction center of purple bacteria Rhodobacter sphaeroides.
AB  - Carotenoid spheroidene (SPO) functions for photoprotection in the photosynthetic
      reaction centers (RCs) and effectively dissipates its triplet excitation energy.
      Sensitized cis-to-trans isomerization was proposed as a possible mechanism for a
      singlet-triplet energy crossing for the 15,15'-cis-SPO; however, it has been
      questioned recently. To understand the dissipative photoprotective mechanism of
      this important SPO and to overcome the existing controversies on this issue, we
      carried out a theoretical investigation using density functional theory on the
      possible triplet energy relaxation mechanism through the cis-to-trans
      isomerization. Together with the earlier experimental observations, the possible
      mechanism was discussed for the triplet energy relaxation of the 15,15'-cis-SPO.
      The result shows that complete cis-to-trans isomerization is not necessary.
      Twisting the C15-C15' bond leads to singlet-triplet energy crossing at
      phi(14,15,15',14') = 77 degrees  with an energy 32.5 kJ mol(-1) (7.7 kcal mol(
      1)) higher than that of the T1 15,15'-cis minimum. Further exploration of the
      minimum-energy intersystem crossing (MEISC) point shows that triplet relaxation
      could occur at a less distorted structure (phi = 58.4 degrees ) with the energy
      height of 26.5 KJ mol(-1) (6.3 kcal mol(-1)). Another important reaction
      coordinate to reach the MEISC point is the bond-length alternation. The model
      truncation effect, solvent effect, and spin-orbit coupling were also
      investigated. The singlet-triplet crossing was also investigated for the 13,14
      cis stereoisomer and locked-13,14-cis-SPO. We also discussed the origin of the
      natural selection of the cis over trans isomer in the RC. 

PMID- 26292637
TI  - Erratum to: Surface functionalization by covalent immobilization of an innovative
      carvacrol derivative to avoid fungal biofilm formation.

PMID- 26292636
TI  - What is the main mechanism of tramadol?
AB  - Tramadol is an analgesic that is used worldwide for pain, but its mechanisms of
      action have not been fully elucidated. The majority of studies to date have
      focused on activation of the MU-opioid receptor (MUOR) and inhibition of
      monoamine reuptake as mechanisms of tramadol. Although it has been speculated
      that tramadol acts primarily through activation of the MUOR, no evidence has
      revealed whether tramadol directly activates the MUOR. During the past decade,
      major advances have been made in our understanding of the physiology and
      pharmacology of ion channels and G protein-coupled receptor (GPCR) signaling.
      Several studies have shown that GPCRs and ion channels are targets for tramadol.
      In particular, tramadol has been shown to affect GPCRs. Here, the effects of
      tramadol on GPCRs, monoamine transporters, and ion channels are presented with a
      discussion of recent research on the mechanisms of tramadol. 

PMID- 26292639
TI  - Tumour immunology: Malaria alters B cell lymphomagenesis.

PMID- 26292638
TI  - Translating nucleic acid-sensing pathways into therapies.
AB  - Nucleic acid sensing by innate receptors initiates immune defences against
      viruses and other pathogens. A hallmark of this response is the release of
      interferons (IFNs), which promote protective immunity by inducing IFN-stimulated
      genes (ISGs). A similar ISG signature is found in autoinflammatory and autoimmune
      conditions, indicating that chronic activation of nucleic acid-sensing pathways
      may contribute to these diseases. Here, we review how nucleic acid-sensing
      pathways are currently being targeted pharmacologically with both agonists and
      antagonists. We discuss how an improved understanding of the biology of these
      pathways is leading to novel therapies for infections, cancer, and autoimmune and
      autoinflammatory disorders, and how new therapeutics will, in turn, generate a
      deeper understanding of these complex diseases. 

PMID- 26292642
TI  - Pediatric Branchial Cleft Cysts: A Case Study.

PMID- 26292644
TI  - Effect of obstructive sleep apnea syndrome on corneal thickness.
AB  - Obstructive sleep apnea syndrome (OSAS) might be a risk factor for the
      development of eye disorders. The aim of the study was to evaluate the effect of
      OSAS on central corneal thickness (CCT). A total of 195 patients were enrolled in
      the study, and underwent polysomnography. Patients were divided according to
      their apnea-hypopnea index (AHI) scores into control group (AHI < 5), mild (AHI,
      5-15), moderate (AHI, 15-30), and severe OSAS (AHI > 30) groups. In
      ophthalmological examinations, CCT, auto refractometer measurement, tear break-up
      time, and Schrimer's test results were evaluated. Central corneal thickness was
      significantly decreased in patients with OSAS compared to the control group
      (542.14 +/- 31.21 vs. 569.92 +/- 13.46, p < 0.001). As the severity of OSAS
      increased, CCT decreased (mild OSAS = 567.48 +/- 23 mm, moderate OSAS = 530.21 +/
      30.2 mm, and severe OSAS = 557.97 +/- 16.52 mm, respectively, p < 0.001). The
      mean values of auto refractometer, tear break-up time, and Schrimer's test were
      similar between the groups (p > 0.05). CCT was negatively correlated with AHI,
      oxygen desaturation index, desaturation percentages, and positively correlated
      with minimum oxygen saturation values (p < 0.05). This study showed that central
      corneal thickness is inversely correlated with the severity of OSAS. OSAS affects
      all organ systems particularly cardiovascular and neurological mechanisms.
      Further studies are warranted to evaluate the effect of OSAS treatment on CCT. 

PMID- 26292643
TI  - About the power of biostatistics in sibling analysis-comparison of empirical and
      simulated data.
AB  - The determination of potential sibship is a common task in routine kinship
      analysis, but often the putative parents are not available for analysis anymore.
      Then, a sibling analysis has to be conducted investigating only the potential
      siblings, thus reducing the power of the conclusion. In an attempt to determine
      meaningfulness of biostatistical calculations, 346 dizygotic twin pairs, 30
      confirmed half siblings, and 112 unrelated people (to generate 6216 pair
      comparisons) were studied, all genetically typed using at least the Powerplex(r)
      16 STRs. From every pair, the probabilities for a full sibship (identical
      parents) and half sibship (different fathers) were calculated using a
      commercially available computer program. Additionally, we simulated marker data
      for one million pairs of full sibs, half sibs, and unrelated persons each. Ninety
      five percent of full sibling pairs demonstrated a likelihood ratio (LR) > 9 (W
      value > 90 %) and less than 4% of these showed a LR < 3 (W-value < 75%) for full
      sibship after analysis of 15 STRs. The results for half siblings are less
      unambiguous. Here, only 57% achieved a LR > 9 and 23% a LR < 3. Regarding the
      unrelated pairs, more than 90% had a LR < 1/9 and only 2% reached a LR > 9. All
      in all, our results show that 15 to 20 STRs have sufficient power for analyses in
      kinship. Moreover, our data provide a statistical basis for the determination of
      the information content of a LR/W-value in a sibship case. Investigating an
      identical number of full siblings and unrelated pairs, it could be shown that 92%
      of pairs with a LR > 9 for full sibship probability really are full siblings. So,
      setting a cutoff level for full sibship at LR > 9, less than 10% of pairs will be
      wrongly assumed as full siblings even though they are unrelated.

PMID- 26292645
TI  - Systemic oxygen therapy versus oral enalapril for treatment of diabetic macular
      ischemia: a randomized controlled trial.
AB  - The purpose of this study was to evaluate the structural and functional effects
      of systemic oxygen therapy and enalapril in patients with diabetic macular
      ischemia (DMI). This randomized clinical trial consisted of 105 eyes with DMI
      divided into three groups. Group I received systemic oxygen by face mask at a
      flow rate of 10 L/min; Group II received 5 mg enalapril daily; and Group III
      received placebo tablets for 3 months. Best-corrected visual acuity (BCVA),
      central macular thickness (CMT) measured by optical coherence tomography (OCT),
      extent of foveal avascular zone (FAZ) on fluorescein angiograms, and
      electroretinograms (ERG) were obtained at baseline and after 3 and 6 months.
      Overall, 102 patients completed the study. Baseline characteristics were not
      significantly different among groups. Significant improvement in BCVA and
      decrease in CMT and FAZ occurred at months 3 and 6 in oxygen group compared to
      deterioration in enalapril and control groups (All P values <0.001). ERG
      parameters were significantly better in oxygen group compared to enalapril group
      at months 3 and 6 and better than those in control group at month 3. Normobaric
      oxygen therapy for 3 months in DMI decreased CMT and FAZ and improved BCVA and
      ERG parameters. Enalapril did not show any favorable effect. 

PMID- 26292646
TI  - Selective Control of the Left Hepatic Vein During Laparoscopic Liver Resection:
      Arentius' Ligament Approach.

PMID- 26292640
TI  - The cytoskeleton in cell-autonomous immunity: structural determinants of host
      defence.
AB  - Host cells use antimicrobial proteins, pathogen-restrictive compartmentalization
      and cell death in their defence against intracellular pathogens. Recent work has
      revealed that four components of the cytoskeleton--actin, microtubules,
      intermediate filaments and septins, which are well known for their roles in cell
      division, shape and movement--have important functions in innate immunity and
      cellular self-defence. Investigations using cellular and animal models have shown
      that these cytoskeletal proteins are crucial for sensing bacteria and for
      mobilizing effector mechanisms to eliminate them. In this Review, we highlight
      the emerging roles of the cytoskeleton as a structural determinant of cell
      autonomous host defence.

PMID- 26292647
TI  - Expert Intraoperative Judgment and Decision-Making: Defining the Cognitive
      Competencies for Safe Laparoscopic Cholecystectomy.
AB  - BACKGROUND: Bile duct injuries from laparoscopic cholecystectomy remain a
      significant source of morbidity and are often the result of intraoperative errors
      in perception, judgment, and decision-making. This qualitative study aimed to
      define and characterize higher-order cognitive competencies required to safely
      perform a laparoscopic cholecystectomy. STUDY DESIGN: Hierarchical and cognitive
      task analyses for establishing a critical view of safety during laparoscopic
      cholecystectomy were performed using qualitative methods to map the thoughts and
      practices that characterize expert performance. Experts with more than 5 years of
      experience, and who have performed at least 100 laparoscopic cholecystectomies,
      participated in semi-structured interviews and field observations. Verbal data
      were transcribed verbatim, supplemented with content from published literature,
      coded, thematically analyzed using grounded-theory by 2 independent reviewers,
      and synthesized into a list of items. RESULTS: A conceptual framework was created
      based on 10 interviews with experts, 9 procedures, and 18 literary sources.
      Experts included 6 minimally invasive surgeons, 2 hepato-pancreatico-biliary
      surgeons, and 2 acute care general surgeons (median years in practice, 11 [range
      8 to 14]). One hundred eight cognitive elements (35 [32%] related to situation
      awareness, 47 [44%] involving decision-making, and 26 [24%] action-oriented
      subtasks) and 75 potential errors were identified and categorized into 6 general
      themes and 14 procedural tasks. Of the 75 potential errors, root causes were
      mapped to errors in situation awareness (24 [32%]), decision-making (49 [65%]),
      or either one (61 [81%]). CONCLUSIONS: This study defines the competencies that
      are essential to establishing a critical view of safety and avoiding bile duct
      injuries during laparoscopic cholecystectomy. This framework may serve as the
      basis for instructional design, assessment tools, and quality-control metrics to
      prevent injuries and promote a culture of patient safety.

PMID- 26292648
TI  - Learning Problem-Solving Rules as Search Through a Hypothesis Space.
AB  - Learning to solve a class of problems can be characterized as a search through a
      space of hypotheses about the rules for solving these problems. A series of four
      experiments studied how different learning conditions affected the search among
      hypotheses about the solution rule for a simple computational problem. Experiment
      1 showed that a problem property such as computational difficulty of the rules
      biased the search process and so affected learning. Experiment 2 examined the
      impact of examples as instructional tools and found that their effectiveness was
      determined by whether they uniquely pointed to the correct rule. Experiment 3
      compared verbal directions with examples and found that both could guide search.
      The final experiment tried to improve learning by using more explicit verbal
      directions or by adding scaffolding to the example. While both manipulations
      improved learning, learning still took the form of a search through a hypothesis
      space of possible rules. We describe a model that embodies two assumptions: (1)
      the instruction can bias the rules participants hypothesize rather than directly
      be encoded into a rule; (2) participants do not have memory for past wrong
      hypotheses and are likely to retry them. These assumptions are realized in a
      Markov model that fits all the data by estimating two sets of probabilities.
      First, the learning condition induced one set of Start probabilities of trying
      various rules. Second, should this first hypothesis prove wrong, the learning
      condition induced a second set of Choice probabilities of considering various
      rules. These findings broaden our understanding of effective instruction and
      provide implications for instructional design.

PMID- 26292649
TI  - Evolution of environmental cues for phenotypic plasticity.
AB  - Phenotypically plastic characters may respond to multiple variables in their
      environment, but the evolutionary consequences of this phenomenon have rarely
      been addressed theoretically. We model the evolution of linear reaction norms in
      response to several correlated environmental variables, in a population
      undergoing stationary environmental fluctuations. At evolutionary equilibrium,
      the linear combination of environmental variables that acts as a developmental
      cue for the plastic trait is the multivariate best linear predictor of changes in
      the optimum. However, the reaction norm with respect to any single environmental
      variable may exhibit nonintuitive patterns. Apparently maladaptive, or
      hyperadaptive plasticity can evolve with respect to single environmental
      variables, and costs of plasticity may increase, rather than reduce, plasticity
      in response to some variables. We also find conditions for the evolution of an
      indirect environmental indicator that affects expression of a plastic phenotype,
      despite not influencing natural selection on it. 

PMID- 26292650
TI  - Undifferentiated Laryngeal Carcinoma with Pagetoid Spread.
AB  - Pagetoid spread, is used to define intraepithelial spread of cancer cells, when a
      massive carcinoma is identified beneath the basal membrane. There are only few
      reports of pagetoid spread at the head and neck region. Herein a 74 year old male
      patient with bilateral transglottic laryngeal high grade malignant epithelial
      tumor with pagetoid spread is presented. The tumor was located at the submucosa
      and there was spread of the CK7 and CK19 positive tumor cells into the non
      neoplastic mucosa, which was CK5/6 positive, sparing the basement membrane,
      creating a typical pagetoid pattern. Radiographic and positron emission
      tomography scan examination of the patient was unremarkable at presentation other
      than the laryngeal and neck lesions; but extensive systemic metastasis developed
      at 6 months following operation. To the best of our knowledge no epithelial
      malignancy with pagetoid spread was described at the larynx. Pagetoid spread may
      be a hallmark of very aggressive behavior in laryngeal carcinoma.

PMID- 26292651
TI  - De novo analysis of the transcriptome of Pratylenchus zeae to identify
      transcripts for proteins required for structural integrity, sensation, locomotion
      and parasitism.
AB  - The root lesion nematode Pratylenchus zeae, a migratory endoparasite, is an
      economically important pest of major crop plants (e.g. cereals, sugarcane). It
      enters host roots, migrates through root tissues and feeds from cortical cells,
      and defends itself against biotic and abiotic stresses in the soil and in host
      tissues. We report de novo sequencing of the P. zeae transcriptome using 454 FLX,
      and the identification of putative transcripts encoding proteins required for
      movement, response to stimuli, feeding and parasitism. Sequencing generated
      347,443 good quality reads which were assembled into 10,163 contigs and 139,104
      singletons: 65% of contigs and 28% of singletons matched sequences of free-living
      and parasitic nematodes. Three-quarters of the annotated transcripts were common
      to reference nematodes, mainly representing genes encoding proteins for
      structural integrity and fundamental biochemical processes. Over 15,000
      transcripts were similar to Caenorhabditis elegans genes encoding proteins with
      roles in mechanical and neural control of movement, responses to chemicals,
      mechanical and thermal stresses. Notably, 766 transcripts matched parasitism
      genes employed by both migratory and sedentary endoparasites in host
      interactions, three of which hybridized to the gland cell region, suggesting that
      they might be secreted. Conversely, transcripts for effectors reported to be
      involved in feeding site formation by sedentary endoparasites were conspicuously
      absent. Transcripts similar to those encoding some secretory-excretory products
      at the host interface of Brugia malayi, the secretome of Meloidogyne incognita
      and products of gland cells of Heterodera glycines were also identified. This P.
      zeae transcriptome provides new information for genome annotation and functional
      analysis of possible targets for control of pratylenchid nematodes.

PMID- 26292652
TI  - Global standards for global health in a globalized economy!

PMID- 26292653
TI  - Factors affecting long-term outcome of transoral surgery for submandibular
      stones: a follow-up study of 125 patients.
AB  - OBJECTIVE: To investigate the long-term results of transoral surgery for
      submandibular stones and assess factors that may affect the long-term outcomes.
      STUDY DESIGN: A follow-up study including retrospective review of medical records
      and prospective telephone survey. SETTING: Tertiary Hospital. PARTICIPANTS: A
      total of 125 patients who had undergone transoral surgery for submandibular
      stones and responded to telephone survey. MAIN OUTCOME MEASURES: Recurrent
      obstructive symptoms, tongue paraesthesia. RESULTS: The period between transoral
      surgery and telephone survey was mean 54.8 months. Eighteen (14.4%) of 125
      patients had recurrent obstructive symptoms, and 7 (5.6%) patients showed tongue
      paraesthesia. Proximal stones (P = 0.041) and partially removed stones (P =
      0.003) had significant impact on the development of recurrent obstructive
      symptoms via multivariate analysis. No significant factors for increased risk of
      tongue paraesthesia were identified. Recurred symptoms could be managed by
      subsequent transoral surgeries or conservative management. CONCLUSIONS: Complete
      removal of proximal stones and gland-preserving management of recurred symptoms
      are the essential elements to achieve good long-term outcome of transoral surgery
      for the submandibular stones.

PMID- 26292654
TI  - CNV Analysis Associates AKNAD1 with Type-2 Diabetes in Jordan Subpopulations.
AB  - Previous studies have identified a number of single nucleotide polymorphisms
      (SNPs) associated with type-2 diabetes (T2D), but copy number variation (CNV)
      association has rarely been addressed, especially in populations from Jordan. To
      investigate CNV associations for T2D in populations in Jordan, we conducted a CNV
      analysis based on intensity data from genome-wide SNP array, including 34 T2D
      cases and 110 healthy controls of Chechen ethnicity, as well as 34 T2D cases and
      106 healthy controls of Circassian ethnicity. We found a CNV region in protein
      tyrosine phosphatase receptor type D (PTPRD) with significant association with
      T2D. PTPRD has been reported to be associated with T2D in genome-wide association
      studies (GWAS). We additionally identified 16 CNV regions associated with T2D
      which overlapped with gene exons. Of particular interest, a CNV region in the
      gene AKNA Domain Containing 1 (AKNAD1) surpassed the experiment-wide significance
      threshold. Endoplasmic reticulum (ER)-related pathways were significantly
      enriched among genes which are predicted to be functionally associated with human
      or mouse homologues of AKNAD1. This is the first CNV analysis of a complex
      disease in populations of Jordan. We identified and experimentally validated a
      significant CNVR in gene AKNAD1 associated with T2D. 

PMID- 26292655
TI  - Central venous pressure and liver resection: a systematic review and meta
      analysis.
AB  - BACKGROUND: A liver resection under low central venous pressure (CVP) has become
      standard practice; however, the benefits beyond a reduction in blood loss are not
      well reported. Moreover, the precise method to achieve CVP reduction has not been
      established. A systematic review and meta-analysis of randomized controlled
      trials (RTCs) was performed to assess the effects of CVP on clinical outcome and
      to identify the optimum method of CVP reduction. METHODS: EMBASE, Medline, PubMed
      and the Cochrane database were searched for trials comparing low CVP surgery with
      controls. The primary outcome was post-operative complications within 30 days.
      Secondary outcomes included estimated blood loss (EBL), blood transfusion rates
      and length of stay (LOS). Sub-group analysis was performed to assess the CVP
      reduction method on the outcome. RESULTS: Eight trials were identified. No
      difference was observed in the morbidity rate between the high CVP and control
      groups [odds ratio (OR) = 0.96 (95% confidence interval (CI) 0.66, 1.40) P =
      0.84, I(2) = 0%]. EBL [weighted mean difference (WMD) = -308.63 ml (95% CI 
      474.67, -142.58) P = < 0.001, I(2) = 73%] and blood transfusion rates [OR 0.65
      (95% CI 0.44, 0.97) P = 0.040, I(2) = 37%] were significantly lower in the low
      CVP groups. Neither anaesthetic nor surgical methods of CVP reduction were
      associated with a reduced post-operative morbidity. CONCLUSION: Low CVP surgery
      is associated with a reduction in EBL; however, this does not translate into an
      improvement in post-operative morbidity. The optimum method of CVP reduction has
      not been identified.

PMID- 26292656
TI  - Prophylactic abdominal drainage for pancreatic surgery.
AB  - BACKGROUND: The use of surgical drains has been considered mandatory after
      pancreatic surgery. The role of prophylactic abdominal drainage to reduce
      postoperative complications after pancreatic surgery is controversial.
      OBJECTIVES: To assess the benefits and harms of routine abdominal drainage after
      pancreatic surgery, compare the effects of different types of surgical drains,
      and evaluate the optimal time for drain removal. SEARCH METHODS: We searched The
      Cochrane Library (2015, Issue 3), MEDLINE (1946 to 9 April 2015), EMBASE (1980 to
      9 April 2015), Science Citation Index Expanded (1900 to 9 April 2015), and
      Chinese Biomedical Literature Database (CBM) (1978 to 9 April 2015). SELECTION
      CRITERIA: We included all randomized controlled trials that compared abdominal
      drainage versus no drainage in patients undergoing pancreatic surgery. We also
      included randomized controlled trials that compared different types of drains and
      different schedules for drain removal in patients undergoing pancreatic surgery.
      DATA COLLECTION AND ANALYSIS: Two review authors independently identified the
      trials for inclusion, collected the data, and assessed the risk of bias. We
      performed the meta-analyses using Review Manager 5. We calculated the risk ratio
      (RR) for dichotomous outcomes and the mean difference (MD) for continuous
      outcomes with 95% confidence intervals (CI). For all analyses, we employed the
      random-effects model. MAIN RESULTS: Drain use versus no drain useWe included two
      trials involving 316 participants who were randomized to the drainage group (N =
      156) and the no drainage group (N = 160) after pancreatic surgery. Both trials
      were at high risk of bias. There was inadequate evidence to establish the effect
      of drains on mortality at 30 days (drains 1.3%; no drains 3.8%; RR 0.44; 95% CI
      0.05 to 3.94; two studies; very low-quality evidence), mortality at 90 days (2.9%
      versus 11.6%; RR 0.24; 95% CI 0.05 to 1.10; one study; very low-quality
      evidence), intra-abdominal infection (8.3% versus 14.4%; RR 0.61; 95% CI 0.25 to
      1.46; two studies), wound infection (10.9% versus 11.9%; RR 0.91; 95% CI 0.45 to
      1.86; two studies), morbidity (67.3% versus 65.0%; RR 1.02; 95% CI 0.88 to 1.19;
      two studies), length of hospital stay (MD -0.97 days; 95% CI -1.41 to -0.53; two
      studies), or additional open procedures for postoperative complications (6.3%
      versus 6.4%; RR 0.90, 95% CI 0.15 to 5.32; two studies). There was one drain
      related complication in the drainage group (0.6%). The quality of evidence was
      low, or very low. Type of drainThere were no randomized controlled trials
      comparing one type of drain versus another. Early versus late drain removalWe
      included one trial involving 114 participants with a low risk of postoperative
      pancreatic fistula who were randomized to the early drain removal group (N = 57)
      and the late drain removal group (N = 57) after pancreatic surgery. The trial was
      at high risk of bias. There was no evidence of differences between the two groups
      in the mortality at 30 days (0% for both groups) or additional open procedures
      for postoperative complications (0% versus 1.8%; RR 0.33; 95% CI 0.01 to 8.01).
      The early drain removal group was associated with lower rates of postoperative
      complications (38.5% versus 61.4%; RR 0.63; 95% CI 0.43 to 0.93), shorter length
      of hospital stay (MD -2.10 days; 95% CI -4.17 to -0.03; 21.5% decrease of an
      'average' length of hospital stay) and hospital costs (17.0% decrease of
      'average' hospital costs) than in the late drain removal group. The quality of
      evidence for each of the outcomes was low. AUTHORS' CONCLUSIONS: It is not clear
      whether routine abdominal drainage has any effect on the reduction of mortality
      and postoperative complications after pancreatic surgery. In case of drain
      insertion, low-quality evidence suggests that early removal may be superior to
      late removal for patients with low risk of postoperative pancreatic fistula.

PMID- 26292657
TI  - Phenotype-Guided Natural Products Discovery Using Cytological Profiling.
AB  - Phenotype-guided natural products discovery is emerging as a useful new discovery
      tool that addresses challenges in early, unbiased natural product biological
      annotation. These high-content approaches yield screening results that report
      directly on the impact of test compounds on cellular processes in target
      organisms and can be used to predict the modes of action of bioactive
      constituents from primary screening data. In this study we explored the use of
      our recently implemented cytological profiling platform for the isolation of
      compounds with a specific, predefined mode of action, namely, induction of
      mitotic arrest. Screening of a microbially derived extract library revealed six
      extracts whose cytological profiles clustered closely with those of known
      antimitotic agents from the pure compound training set. Subsequent examination of
      one of these extracts revealed the presence of two separate bioactive
      constituents, each of which possessed a unique cytological profile. The first,
      diketopiperazine XR334 (3), recapitulated the observed antimitotic phenotype of
      the original extract, demonstrating that cytological profiling can be used for
      the targeted isolation of compounds with specific modes of action. The second,
      nocapyrone L (6), possessed a cytological profile that clustered with known
      calcium channel modulators, in line with previous published activities for this
      compound class, indicating that cytological profiling is a flexible and powerful
      platform for the de novo characterization of compound modes of action. 

PMID- 26292658
TI  - Commentary on the 2015 SPR Standards of Evidence.
AB  - We comment on the 2015 Society for Prevention Research standards of evidence
      document, summarizing major changes from the previous 2005 Standards, and point
      to ways in which the Standards could be further improved. We endorse important
      new standards, such as those on testing the causal theory and mechanisms of the
      intervention, improved trial reporting standards, and added attention to scale-up
      research and cost analyses. Despite discussion of replication in the new
      Standards, we are concerned about the lack of stand-alone replication standards,
      and the deletion of an explicit requirement for replication before an
      intervention is considered efficacious. Finally, we are deeply concerned about
      the lack of attention to the unit or level of aggregation of the intervention
      target. It is a major conceptual oversight. The unit targeted by an intervention
      (whether a cell, person, organization, community, state, nation) is a fundamental
      feature shaping intervention theory, research design, data collection, analyses,
      effect sizes, diffusion possibilities and patterns, and scale-up issues. Future
      Standards updates should eliminate the implicit assumption in the current text
      that effective preventive interventions inherently target individual persons. 

PMID- 26292659
TI  - Evaluation of a Community-Based Approach to Strengthen Retention in Early
      Childhood Home Visiting.
AB  - Home visiting (HV) is a strategy for delivering services designed to promote
      positive parenting and prevent exposure to toxic stress during a critical period
      of child development. Home visiting programs are voluntary and family engagement
      and retention in service can influence outcomes. Most participants receive less
      home visits and for a shorter time than prescribed by evidence-based models. The
      purpose of this study was to evaluate community-based enrichment of HV (CBE-HV),
      an approach that was developed and implemented to increase engagement and
      retention in HV. CBE-HV strategies included (1) community engagement, (2)
      ancillary supports for families in HV, and (3) enhancements to a HV program. A
      retrospective, quasi-experimental study was conducted to estimate the effect of
      CBE-HV on the retention of families in a HV program. Comparisons of study
      participants were made post-implementation of CBE-HV (n = 2191) and over time (n
      = 3786)-pre- versus post-CBE-HV implementation in the study communities. The CBE
      HV effect was statistically significant and protective (hazards ratio [HR] 0.77,
      95 % confidence interval [CI]: 0.67, 0.88), indicating that attrition from HV was
      23 % less in the CBE-HV group relative to the post-implementation comparison
      group. In the temporal comparison of study communities, CBE-HV was also
      associated with a significantly lower risk of HV attrition (HR: 0.71, 95 % CI:
      0.56, 0.89). The study demonstrated that CBE-HV is a promising approach to
      achieve stronger retention and engagement in HV. Further research is needed to
      identify the components of CBE-HV approaches that are most effective.

PMID- 26292660
TI  - Nickel and cobalt release from metal alloys of tools--a current analysis in
      Germany.
AB  - BACKGROUND: The former 'EU Nickel Directive' and, since 2009, the REACH
      Regulation (item 27 of Annex XVII) do not include all metallic objects. The
      nickel content of tools is not regulated by the REACH Regulation, even if they
      may come into in prolonged contact with the skin. Tools might be possible sources
      of nickel and cobalt sensitization, and may contribute to elicitation and
      maintenance of hand eczema. OBJECTIVES: To perform a current analysis of the
      frequency of nickel or cobalt release from new handheld tools purchased in
      Germany. METHODS: Six hundred unused handheld tools from the German market were
      investigated with the dimethylglyoxime test for nickel release and with disodium
      1-nitroso-2-naphthol-3,6-disulfonate solution for cobalt release. RESULTS: Nickel
      release was detected in 195 of 600 (32.5%) items, and cobalt in only six (1%) of
      them. Positive nickel results were nearly twice as frequent in tools 'made in
      Germany' than in tools without a mark of origin. Tools made in other European
      countries did not release nickel. Cobalt release was only found in pliers and a
      saw. A correlation was found between price level and nickel release. Among
      toolkits, 34.2% were inhomogeneous concerning nickel release. CONCLUSION: The
      German market currently provides a large number of handheld tools that release
      nickel, especially tools 'made in Germany'. For consumer protection, it seems
      appropriate to include handheld tools in the REACH Regulation on nickel.

PMID- 26292661
TI  - Putative binding sites for arachidonic acid on the human cardiac Kv 1.5 channel.
AB  - BACKGROUND AND PURPOSE: In human heart, the Kv 1.5 channel contributes to
      repolarization of atrial action potentials. This study examined the
      electrophysiological and molecular mechanisms underlying arachidonic acid (AA)
      induced inhibition of the human Kv 1.5 (hKv 1.5) channel. EXPERIMENTAL APPROACH:
      Site-directed mutagenesis was conducted to mutate amino acids that reside within
      the pore domain of the hKv 1.5 channel. Whole-cell patch-clamp method was used to
      record membrane currents through wild type and mutant hKv 1.5 channels
      heterologously expressed in CHO cells. Computer docking simulation was conducted
      to predict the putative binding site(s) of AA in an open-state model of the Kv
      1.5 channel. KEY RESULTS: The hKv 1.5 current was minimally affected at the onset
      of depolarization but was progressively reduced during depolarization by the
      presence of AA, suggesting that AA acts as an open-channel blocker. AA itself
      affected the channel at extracellular sites independently of its metabolites and
      signalling pathways. The blocking effect of AA was attenuated at pH 8.0 but not
      at pH 6.4. The blocking action of AA developed rather rapidly by co-expression of
      Kv beta1.3. The AA-induced block was significantly attenuated in H463C, T480A,
      R487V, I502A, I508A, V512A and V516A, but not in T462C, A501V and L510A mutants
      of the hKv 1.5 channel. Docking simulation predicted that H463, T480, R487, I508,
      V512 and V516 are potentially accessible for interaction with AA. CONCLUSIONS AND
      IMPLICATIONS: AA itself interacts with multiple amino acids located in the pore
      domain of the hKv 1.5 channel. These findings may provide useful information for
      future development of selective blockers of hKv 1.5 channels.

PMID- 26292662
TI  - Melatonin decreases breast cancer metastasis by modulating Rho-associated kinase
      protein-1 expression.
AB  - The occurrence of metastasis, an important breast cancer prognostic factor,
      depends on cell migration/invasion mechanisms, which can be controlled by
      regulatory and effector molecules such as Rho-associated kinase protein (ROCK-1).
      Increased expression of this protein promotes tumor growth and metastasis, which
      can be restricted by ROCK-1 inhibitors. Melatonin has shown oncostatic,
      antimetastatic, and anti-angiogenic effects and can modulate ROCK-1 expression.
      Metastatic and nonmetastatic breast cancer cell lines were treated with melatonin
      as well as with specific ROCK-1 inhibitor (Y27632). Cell viability, cell
      migration/invasion, and ROCK-1 gene expression and protein expression were
      determined in vitro. In vivo lung metastasis study was performed using female
      athymic nude mice treated with either melatonin or Y27832 for 2 and 5 wk. The
      metastases were evaluated by X-ray computed tomography and single photon emission
      computed tomography (SPECT) and by immunohistochemistry for ROCK-1 and
      cytokeratin proteins. Melatonin and Y27632 treatments reduced cell viability and
      invasion/migration of both cell lines and decreased ROCK-1 gene expression in
      metastatic cells and protein expression in nonmetastatic cell line. The numbers
      of 'hot' spots (lung metastasis) identified by SPECT images were significantly
      lower in treated groups. ROCK-1 protein expression also was decreased in
      metastatic foci of treated groups. Melatonin has shown to be effective in
      controlling metastatic breast cancer in vitro and in vivo, not only via
      inhibition of the proliferation of tumor cells but also through direct antagonism
      of metastatic mechanism of cells rendered by ROCK-1 inhibition. When Y27632 was
      used, the effects were similar to those found with melatonin treatment. 

PMID- 26292664
TI  - Quality in Colonoscopy.
AB  - Quality metrics in colonoscopy are a growing area of focus given the development
      of and need for associated reporting and potential financial penalties. Three
      areas specifically have been identified as important by a multi-society task
      force, and the evidence behind each has been presented here. These metrics are
      adenoma detection rate, appropriate screening interval, and cecal intubation
      rate. Additional factors of interest include bowel preparation cleanliness and
      endoscope withdrawal time. Multifaceted interventions have been implemented to
      improve outcomes in colonoscopy with mixed success. Given that there are some
      quality metrics that have been shown to impact colorectal cancer outcomes,
      additional research should focus on disseminating these methods in a consistent
      and effective way across a myriad of practice models and patient populations. 

PMID- 26292663
TI  - Knockdown of NAT12/NAA30 reduces tumorigenic features of glioblastoma-initiating
      cells.
AB  - BACKGROUND: Glioblastoma (GBM) is the most common primary brain malignancy and
      confers a dismal prognosis. GBMs harbor glioblastoma-initiating cells (GICs) that
      drive tumorigenesis and contribute to therapeutic resistance and tumor
      recurrence. Consequently, there is a strong rationale to target this cell
      population in order to develop new molecular therapies against GBM. Accumulating
      evidence indicates that Nalpha-terminal acetyltransferases (NATs), that are
      dysregulated in numerous human cancers, can serve as therapeutic targets.
      METHODS: Microarrays were used to study the expression of several NATs including
      NAT12/NAA30 in clinical samples and stem cell cultures. The expression of
      NAT12/NAA30 was analyzed using qPCR, immunolabeling and western blot. We
      conducted shRNA-mediated knockdown of NAT12/NAA30 gene in GICs and studied the
      effects on cell viability, sphere-formation and hypoxia sensitivity. Intracranial
      transplantation to SCID mice enabled us to investigate the effects of NAT12/NAA30
      depletion in vivo. Using microarrays we identified genes and biochemical pathways
      whose expression was altered upon NAT12/NAA30 down-regulation. RESULTS: While
      decreased expression of the distal 3'UTR of NAT12/NAA30 was generally observed in
      GICs and GBMs, this gene was strongly up-regulated at the protein level in GBM
      and GICs. The increased protein levels were not caused by increased levels of the
      steady state mRNA but rather by other mechanisms. Also, shorter 3'UTR of
      NAT12/NAA30 correlated with poor survival in glioma patients. As well, we
      observed previously not described nuclear localization of this typically
      cytoplasmic protein. When compared to non-silencing controls, cells featuring
      NAT12/NAA30 knockdown exhibited reduced cell viability, sphere-forming ability,
      and mitochondrial hypoxia tolerance. Intracranial transplantation showed that
      knockdown of NAT12/NAA30 resulted in prolonged animal survival. Microarray
      analysis of the knockdown cultures showed reduced levels of HIF1alpha and altered
      expression of several other genes involved in the hypoxia response. Furthermore,
      NAT12/NAA30 knockdown correlated with expressional dysregulation of genes
      involved in the p53 pathway, ribosomal assembly and cell proliferation. Western
      blot analysis revealed reduction of HIF1alpha, phospho-MTOR(Ser2448) and higher
      levels of p53 and GFAP in these cultures. CONCLUSION: NAT12/NAA30 plays an
      important role in growth and survival of GICs possibly by regulating hypoxia
      response (HIF1alpha), levels of p-MTOR (Ser2448) and the p53 pathway.

PMID- 26292665
TI  - Using Genetics to Identify Hereditary Colorectal Polyposis and Cancer Syndromes
      in Your Patient.
AB  - The majority of patients with colorectal polyps and cancer do not have a
      Mendelian cause of the disease. Age, lifestyle, and environmental factors
      interact with complex genetic traits to contribute to the etiology. However,
      approximately 5-10 % of patients with colorectal cancer (CRC) and more than 40 %
      of patients meeting specific clinical features of the hereditary polyposis
      syndromes have a discoverable, actionable genetic cause which will significantly
      alter their medical management. 

PMID- 26292666
TI  - Meta-Analysis-Based Guidance for Dietary Management in Eosinophilic Esophagitis.
AB  - Eosinophilic esophagitis (EoE) is a prevalent chronic esophageal disorder,
      triggered and maintained by immunologically mediated responses against dietary
      antigens. EoE represents the most recent form of food allergy, and its control by
      avoiding offending foods has increasingly appeared as a therapeutic alternative
      to achieve and maintain remission. Dietary therapies have proved equally
      effective in pediatric and adult EoE patients, among whom various types of
      interventions to eliminate or reduce food antigens exposure have been evaluated.
      A recent meta-analysis showed elemental diet as the most effective option to
      induce disease remission, but with a limited application in clinical practice.
      Inconsistency and wide variability in results from skin allergy testing-directed
      food restriction contributed to dissatisfaction with implementation of this
      option, which subsequently was displaced by empiric elimination of common food
      allergens. Such empiric elimination of common food allergens is now recognized as
      the best alternative for dietary treatment, with moderate-to-high efficiency and
      reproducible results. This review provides evidence-based insights into the
      dietary management of EoE. 

PMID- 26292668
TI  - S100A4 hypomethylation affects epithelial-mesenchymal transition partially
      induced by LMP2A in nasopharyngeal carcinoma.
AB  - To identify cellular target genes involved in NPC cell invasion and metastasis,
      gene expression profiles of CNE-1 cells with or without ectopic LMP2A expression
      were compared by using the metastatic gene array. S100 calcium binding protein A4
      (S100A4) was the highest increased one among these genes both in mRNA and protein
      levels of NPC cells. Moreover, S100A4 was upregulated in LMP2A-positive NPC
      tissues. We found that CNE-1-S100A4 showed significantly increased invasion
      ability as compared to the controls both in vitro and in vivo, which indicated
      that S100A4 induced EMT occurrence and promoted metastasis. Notably, the DNA
      hypomethylation of S100A4 was found in LMP2A-positive NPC tissues. Besides,
      inhibition of DNA methyltransferases via 5-Aza-dC stimulated the expression of
      S100A4 in the cells without ectopic LMP2A expression. The methylation changes
      were confirmed by methylation specific PCR (MSP), suggesting that LMP2A ectopic
      expression led to the demethylation of S100A4 promoter. These results
      demonstrated that LMP2A-induced hypomethylation participated in regulating S100A4
      expression in NPC. Our findings provide an evidence for the emerging notion that
      hypomethylation and activation of correlated genes are crucial for metastasis
      progression in cancer. (c) 2015 Wiley Periodicals, Inc.

PMID- 26292669
TI  - Surface evolution of manganese chloride aqueous droplets resulting in self
      suppressed evaporation.
AB  - The exchange kinetics of liquid water, which are of fundamental interest and have
      potential applications, remain unclear. A fantastic and extraordinary phenomenon
      was observed during the evaporation of a water droplet doped with manganese
      chloride. As observed from the evolution of this type of droplet, a thin film was
      formed on the surface with an exothermic phase transition, resulting in self
      suppressed evaporation. The MnCl2-doped water droplets were maintained in a
      relative humidity (RH) of 50% at 40  degrees C for more than a week and for
      longer than two months at a temperature of 25  degrees C. In contrast, a pure
      water droplet can only be sustained for a few minutes. The self-suppressed
      evaporation of doped water may be due to the special hydration of the accumulated
      manganese and chloride ions at the surface, decreasing the surface tension. 

PMID- 26292667
TI  - Rare variant discovery by deep whole-genome sequencing of 1,070 Japanese
      individuals.
AB  - The Tohoku Medical Megabank Organization reports the whole-genome sequences of
      1,070 healthy Japanese individuals and construction of a Japanese population
      reference panel (1KJPN). Here we identify through this high-coverage sequencing
      (32.4 * on average), 21.2 million, including 12 million novel, single-nucleotide
      variants (SNVs) at an estimated false discovery rate of <1.0%. This detailed
      analysis detected signatures for purifying selection on regulatory elements as
      well as coding regions. We also catalogue structural variants, including 3.4
      million insertions and deletions, and 25,923 genic copy-number variants. The
      1KJPN was effective for imputing genotypes of the Japanese population genome
      wide. These data demonstrate the value of high-coverage sequencing for
      constructing population-specific variant panels, which covers 99.0% SNVs of minor
      allele frequency >=0.1%, and its value for identifying causal rare variants of
      complex human disease phenotypes in genetic association studies. 

PMID- 26292670
TI  - Understanding effective care management implementation in primary care: a
      macrocognition perspective analysis.
AB  - BACKGROUND: Care management in primary care can be effective in helping patients
      with chronic disease improve their health status. Primary care practices,
      however, are often challenged with its implementation. Incorporating care
      management involves more than a simple physical process redesign to existing
      clinical care routines. It involves changes to who is working with patients, and
      consequently such things as who is making decisions, who is sharing patient
      information, and how. Studying the range of such changes in "knowledge work"
      during implementation requires a perspective and tools designed to do so. We used
      the macrocognition perspective, which is designed to understand how individuals
      think in dynamic, messy real-world environments such as care management
      implementation. To do so, we used cognitive task analysis to understand
      implementation in terms of such thinking as decision making, knowledge, and
      communication. METHODS: Data collection involved semi-structured interviews and
      observations at baseline and at approximately 9 months into implementation at
      five practices in one physician-owned administratively connected group of
      practices in the state of Michigan, USA. Practices were intervention participants
      in a larger trial of chronic care model implementation. Data were transcribed,
      qualitatively coded and analyzed, initially using an editing approach and then a
      template approach with macrocognition as a guiding framework. RESULTS: Seventy
      four interviews and five observations were completed. There were differences in
      implementation success across the practices, and these differences in
      implementation success were well explained by macrocognition. Practices that used
      more macrocognition functions and used them more often were also more successful
      in care management implementation. CONCLUSIONS: Although care management can
      introduce many new changes into the delivery of primary care clinical practice,
      implementing it successfully as a new complex intervention is possible.
      Macrocognition is a useful perspective for illuminating the elements that
      facilitate new complex interventions with a view to addressing them during
      implementation planning.

PMID- 26292671
TI  - Editorial-nanoparticles for diagnostic imaging and radiotherapy.

PMID- 26292672
TI  - Distinct Responses of Cytotoxic Ganoderma lucidum Triterpenoids in Human
      Carcinoma Cells.
AB  - The medicinal mushroom Ganoderma lucidum is well recognized for its effective
      cancer-preventative and therapeutic properties, while specific components
      responsible for these anticancer effects are not well studied. Six triterpenoids
      that are ganolucidic acid E, lucidumol A, ganodermanontriol, 7-oxo-ganoderic acid
      Z, 15-hydroxy-ganoderic acid S, and ganoderic acid DM were isolated and
      identified from an extract of the mushroom. All compounds reduced cell growth in
      three human carcinoma cells (Caco-2, HepG2, and HeLa cells) dose dependently with
      LC50s from 20.87 to 84.36 MUM. Moreover, the six compounds induced apoptosis in
      HeLa cells with a maximum increase (22%) of sub-G1 accumulations and 43.03%
      apoptotic cells in terminal deoxynucleotidyl transferase dUTP nick end labeling
      (TUNEL) assay (15-hydroxy-ganoderic acid S treatment). Apoptosis was further
      confirmed by annexin-V staining. Four of the compounds also caused apoptosis in
      Caco-2 cells with maximum 9.5% increase of sub-G1 accumulations (7-oxo-ganoderic
      acid Z treatment) and maximum 29.84% apoptotic cells in TUNEL assay (ganoderic
      acid DM treatment). Contrarily, none of the compounds induced apoptosis in HepG2
      cells. The different responses of the three cell lines following these treatments
      indicated that the bioactive properties of these compounds may vary from cells of
      different sites of origin and are likely acting under diverse regulatory
      mechanisms.

PMID- 26292673
TI  - Preterm birth among the Hmong, other Asian subgroups and non-Hispanic whites in
      California.
AB  - BACKGROUND: We investigated very preterm (VPTB) and preterm birth (PTB) risk
      among Hmong women relative to non-Hispanic whites and other Asian subgroups. We
      also examined the maternal education health gradient across subgroups. METHODS:
      California birth record data (2002-2004) were used to analyze 568,652 singleton
      births to white and Asian women. Pearson Chi-square and logistic regression were
      used to assess variation in maternal characteristics and VPTB/PTB risk by
      subgroup. RESULTS: White, Chinese, Japanese, Korean, Asian Indian, and Vietnamese
      women had 36-59% lower odds of VPTB and 30-56% lower odds of PTB than Hmong
      women. Controls for covariates did not substantially diminish these disparities.
      Cambodian, Filipino and Lao/Thai women's odds of VPTB were similar to that of
      Hmong women. But they had higher adjusted odds of PTB compared to the Hmong.
      There was heterogeneity in the educational gradient of PTB, with significant
      differences between the least and most educated women among whites, Chinese,
      Japanese, Asian Indians, Cambodians, and Laoians/Thais. Maternal education was
      not associated with PTB for Hmong, Vietnamese and Korean women, however.
      CONCLUSIONS: Studies of Hmong infant health from the 1980s, the decade
      immediately following the group's mass migration to the US, found no significant
      differences in adverse birth outcomes between Hmong and white women. By the early
      2000s, however, the disparities in VPTB and PTB between Hmong and white women, as
      well as between Hmong and other Asian women had become substantial. Moreover,
      despite gains in post-secondary education among childbearing-age Hmong women, the
      returns to education for the Hmong are negligible. Higher educational attainment
      does not confer the same health benefits for Hmong women as it does for whites
      and other Asian subgroups.

PMID- 26292674
TI  - HypoAware-a brief and partly web-based psycho-educational group intervention for
      adults with type 1 and insulin-treated type 2 diabetes and problematic
      hypoglycaemia: design of a cost-effectiveness randomised controlled trial.
AB  - BACKGROUND: Problematic hypoglycaemia is a significant problem among people with
      insulin-treated type 1 and 2 diabetes mellitus, which adversely affects quality
      of life and leads to high societal costs. Blood glucose awareness training (BGAT)
      is a psycho-educational group intervention that has shown to be effective but
      difficult to implement in clinical practice, due to its demanding nature. The aim
      of this study is to evaluate the cost-effectiveness of the HypoAware intervention
      that has its roots in BGAT and helps patients to effectively recognize, treat and
      prevent hypoglycaemia, while also focussing on the psychosocial consequences of
      living with the constant risk of hypoglycaemia, both for patients and their
      significant others. METHODS/DESIGN: An economic evaluation will be conducted
      alongside a cluster-randomised controlled trial in eight hospitals in the
      Netherlands. We aim to include 154 participants who will either receive HypoAware
      or care as usual. HypoAware consists of three group sessions and is combined with
      two online modules. The primary clinical outcome is severe hypoglycaemia.
      Secondary outcomes include mild hypoglycaemia, hypoglycaemia awareness, fear of
      hypoglycaemia, diabetes distress, anxiety and depression, health-related quality
      of life, diabetes-specific self-efficacy and HbA1c. Utilities will be measured
      using the EQ-5D-5 L questionnaire. Costs will be measured from a societal
      perspective and include health care utilization, medication and lost productivity
      costs. Measurements will be performed at baseline, 2, 4, and 6 months to compare
      both groups, and an additional 12 months for the intervention group only. Process
      outcomes will be gathered after every group meeting via telephone/email contact
      with health care professionals and via the online environment. DISCUSSION:
      HypoAware is expected to significantly reduce episodes of severe hypoglycaemia,
      with subsequent beneficial effects on psychosocial outcomes and health care
      costs. When proven cost-effective, HypoAware will be incorporated in the clinical
      guidelines of Dutch diabetes care. TRIAL REGISTRATION: Dutch Trial Register
      NTR4538.

PMID- 26292675
TI  - Engaging teenagers in improving their health behaviours and increasing their
      interest in science (Evaluation of LifeLab Southampton): study protocol for a
      cluster randomized controlled trial.
AB  - BACKGROUND: Lifestyle and health behaviours are strongly linked to non
      communicable disease risk, but modifying them is challenging. There is an
      increasing recognition that adolescence is an important time for lifestyle and
      health behaviours to become embedded. Improving these behaviours in adolescents
      is important not only for their own health but also for that of their future
      children. LifeLab Southampton has been developed as a purpose-built classroom and
      laboratory in University Hospital Southampton. Secondary school students visit
      LifeLab to learn how childhood, adolescent and parental nutrition influences
      health, understand the impact of their lifestyle on their cardiovascular and
      metabolic health, and to inspire them with the excitement of research and future
      career possibilities in science. The LifeLab visit is part of a programme of work
      linked to the English National Curriculum. Pilot work has indicated that
      attitudes towards health can be changed by such LifeLab sessions. METHODS/DESIGN:
      A cluster randomised controlled trial is being conducted to evaluate the
      effectiveness of the LifeLab intervention, the primary outcome being a
      measurement of the change in nutrition, health and lifestyle literacy from before
      to after the LifeLab intervention. The LifeLab intervention comprises
      professional development for the teachers involved; preparatory lessons for the
      school students, delivered in school; a hands-on practical day at LifeLab,
      including a 'Meet the Scientist' session; post-visit lessons delivered in school;
      and the opportunity to participate in the annual LifeLab Schools' Conference.
      This study aims to recruit approximately 2,500 secondary school students aged 13
      to 14 years from 32 schools (the clusters) from Southampton and neighbouring
      areas. Participating schools will be randomised to control or intervention
      groups. The intervention will be run over two academic school years, with
      baseline questionnaire data collected from students at participating schools at
      the start of the academic year and follow- up questionnaire data collected
      approximately 12 months later. TRIAL REGISTRATION: Evaluation of LifeLab is a
      cluster randomised controlled trial ( ISRCTN71951436 , registered 25 March 2015),
      funded by the British Heart Foundation (PG/14/33/30827).

PMID- 26292692
TI  - Full-movement neuromuscular electrical stimulation improves plantar flexor
      spasticity and ankle active dorsiflexion in stroke patients: a randomized
      controlled study.
AB  - OBJECTIVE: To investigate whether full-movement neuromuscular electrical
      stimulation, which can generate full range of movement, reduces spasticity and/or
      improves motor function more effectively than control, sensory threshold
      neuromuscular electrical stimulation, and motor threshold-neuromuscular
      electrical stimulation in sub-acute stroke patients. DESIGN: A randomized, single
      blind, controlled study. SETTING: Physical therapy room and functional assessment
      room. PARTICIPANTS: A total of 72 adult patients with sub-acute post-stroke
      hemiplegia and plantar flexor spasticity. METHOD: Patients received 30-minute
      sessions of neuromuscular electrical stimulation on the motor points of the
      extensor hallucis and digitorum longus twice a day, five days per week for four
      weeks. MEASURES: Composite Spasticity Scale, Ankle Active Dorsiflexion Score, and
      walking time in the Timed Up and Go Test were assessed at pretreatment,
      posttreatment, and at two-week follow-up. RESULTS: After four weeks of treatment,
      when comparing interclass pretreatment and posttreatment, only the full-movement
      neuromuscular electrical stimulation group had a significant reduction in the
      Composite Spasticity Scale (mean % reduction = 19.91(4.96)%, F = 3.878, p < 0.05)
      and improvement in the Ankle Active Dorsiflexion Score (mean scores = 3.29(0.91),
      F = 3.140, p < 0.05). Furthermore, these improvements were maintained two weeks
      after the treatment ended. However, there were no significant differences in the
      walking time after four weeks of treatment among the four groups (F = 1.861, p >
      0.05). CONCLUSIONS: Full-movement neuromuscular electrical stimulation with a
      stimulus intensity capable of generating full movement can significantly reduce
      plantar flexor spasticity and improve ankle active dorsiflexion, but cannot
      decrease walking time in the Timed Up and Go Test in sub-acute stroke patients.

PMID- 26292691
TI  - Obesity as a Determinant of Staphylococcus aureus Colonization Among Inmates in
      Maximum-Security Prisons in New York State.
AB  - Obesity increases a person's susceptibility to a variety of infections, including
      Staphylococcus aureus infections, which is an important cause of morbidity in
      correctional settings. Using a cross-sectional design, we assessed the
      association between obesity and S. aureus colonization, a risk factor for
      subsequent infection, in New York State maximum-security prisons (2011-2013).
      Anterior nares and oropharyngeal cultures were collected. Structured interviews
      and medical records were used to collect demographic, behavioral, and medical
      data. Body mass index (BMI; weight (kg)/height (m(2))) was categorized as 18.5
      24.9, 25-29.9, 30-34.9, or >=35. The association between BMI and S. aureus
      colonization was assessed using log-binomial regression. Thirty-eight percent of
      638 female inmates and 26% of 794 male inmates had a BMI of 30 or higher. More
      than 40% of inmates were colonized. Female inmates with a BMI of 25-29.9
      (prevalence ratio (PR) = 1.37, 95% confidence interval (CI): 1.06, 1.76), 30-34.9
      (PR = 1.52, 95% CI: 1.17, 1.98), or >=35 (PR = 1.49, 95% CI: 1.13, 1.96) had a
      higher likelihood of colonization than did those with a BMI of 18.5-24.9 after we
      controlled for age, educational level, smoking status, diabetes status, and
      presence of human immunodeficiency virus. Colonization was higher among male
      inmates with a BMI of 30-34.9 (PR = 1.27, 95% CI: 1.01, 1.61). Our findings
      demonstrate an association between BMI and S. aureus colonization among female
      prisoners. Potential contributory biologic and behavioral factors should be
      explored. 

PMID- 26292693
TI  - Identifying depression post-stroke in patients with aphasia: a systematic review
      of the reliability, validity and feasibility of available instruments.
AB  - OBJECTIVE: To identify and critically appraise the evidence for instruments
      assessing depression in stroke patients with aphasia. METHODS: The PubMed,
      CINAHL, Web of Science, Psych Info and Cochrane databases were searched from
      inception until May 2015. RESULTS: Of the 383 titles found in the search, 15
      articles met the inclusion criteria and six instruments were identified: The
      Aphasic Depression Rating Scale, the Clinical Global Impression-Scale, the Stroke
      Aphasic Depression Questionnaire (four versions), the Signs of Depression Scale,
      the Visual Analogue Mood Scale (three versions) and the Visual Analogue Self
      Esteem Scale. Supporting evidence for reliability and validity was limited owing
      to methodological flaws in the studies influencing the ratings of methodological
      quality. Feasibility data were available for all instruments. Rating time of the
      instruments ranged from less than one minute to five minutes, two instruments
      required extensive training. CONCLUSION: A number of instruments to assess
      depressive symptoms in patients with aphasia are available. None of the
      instruments however, were found to be sufficiently investigated and most of the
      studies identified were of low methodological quality. Given the present
      evidence, the Stroke Aphasic Depression Questionnaire-10, the Stroke Aphasic
      Depression Questionnaire-H10 and the Signs of Depression Scale are the most
      feasible and can be recommended for clinical practice.

PMID- 26292694
TI  - Changes in secondary hyperparathyroidism-related biochemical parameters and
      medication use following parathyroidectomy.
AB  - BACKGROUND: Little is known about changes in parathyroid hormone (PTH), calcium
      and phosphorous levels after parathyroidectomy in hemodialysis patients. We
      studied the effects of parathyroidectomy on these biochemical values in a large
      cohort of patients receiving maintenance hemodialysis. METHODS: This
      retrospective cohort study included patients identified in both the United States
      Renal Data System and the database of a large dialysis organization who underwent
      parathyroidectomy in 2007-09, were aged >= 18 years, had Medicare Parts A and B
      as primary payer and had received hemodialysis for >= 1 year pre
      parathyroidectomy. Descriptive statistics were calculated for continuous
      variables; categorical variables were used to characterize the population and
      evaluate monthly laboratory and medication use; median values were calculated for
      laboratory measures. RESULTS: Among 1402 parathyroidectomy patients, mean age was
      48.9 years, 52.4% were males, 58.8% were African American and mean dialysis
      duration was 7.5 years. Median PTH levels increased over the year before
      parathyroidectomy from 1039 to 1661 pg/mL and decreased afterward to 98 pg/mL at
      1 month; levels remained >= 897 pg/mL for 10% of patients. Median calcium levels
      fell from 9.6 mg/dL before to 7.9 mg/dL 1 month after parathyroidectomy; levels
      were <= 7.1 mg/dL for 25% and remained <= 7.2 mg/dL for the lowest 25% at 3
      months. Median phosphorous level was 6.8 mg/dL immediately before
      parathyroidectomy, decreased to 3.8 mg/dL immediately after and reached 5.8 mg/dL
      at 1 year. CONCLUSIONS: While PTH levels dropped after parathyroidectomy for most
      patients, surgery was sometimes ineffective in reducing levels and sometimes led
      to over-suppression. Hypocalcemia could be profound and long lasting, suggesting
      the need for prolonged vigilance.

PMID- 26292695
TI  - The Other Half of Informed Consent: Transplant Education Practices in Dialysis
      Centers.

PMID- 26292697
TI  - Current and future molecular profiling of cancer by next-generation sequencing.
AB  - Advances in the new sequencing technologies have enabled us to explore global
      genetic alterations including driver genes in a wide range of cancers.
      Concordantly, successes of molecular target therapy promoted the validity of
      tumor classification based on the combination of targetable genetic
      abnormalities, and next-generation sequencing-based genetic profiling using
      target gene capturing or multiplex-polymerase chain reaction has already been
      tested or adapted in many cancer centers. Driver gene-based classification may be
      applicable beyond organs, and clinical trials incorporating this genomic
      information, called as a basket trial, have been executed, although it should be
      considered that similar therapeutic efficacies against driver mutations are not
      invariably maintained among different cancer types. Research efforts to identify
      still missing driver genes in rare cancers, to complete functional annotation of
      infrequent driver genes, and multiple-layered omics approaches are further
      expected for better classification of tumor. Emerging clinical interests in the
      development of immunotherapies postulate a new molecular classification of
      tumors. Recent studies reported that total number of mutations and the frequent
      appearance of neo-antigens by protein-coding mutations were associated with a
      better response, and genetic evaluation of both tumor and host immune system by
      sequencing is expected to contribute to the personalized immunotherapies in the
      near future. Lastly intratumoral molecular heterogeneity challenges the current
      'static' molecular classification of tumor. For example, dynamic change in clonal
      constitution within tumor plays an important role in acquired drug resistance. It
      has been extensively explored whether liquid biopsy-based molecular profiling can
      resolve currently confronting difficulties. 

PMID- 26292696
TI  - Assessing Transplant Education Practices in Dialysis Centers: Comparing Educator
      Reported and Medicare Data.
AB  - BACKGROUND AND OBJECTIVES: The Centers for Medicare & Medicaid Services (CMS)
      requires that dialysis centers inform new patients of their transplant options
      and document compliance using the CMS-2728 Medical Evidence Form (Form-2728).
      This study compared reports of transplant education for new dialysis patients
      reported to CMS with descriptions from transplant educators (predominantly
      dialysis nurses and social workers) of their centers' quantity of and specific
      educational practices. The goal was to determine what specific transplant
      education occurred and whether provision of transplant education was associated
      with center-level variation in transplant wait-listing rates. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: Form-2728 data were drawn for 1558 incident
      dialysis patients at 170 centers in the Heartland Kidney Network (Iowa, Kansas,
      Missouri, and Nebraska) in 2009-2011; educators at these centers completed a
      survey describing their transplant educational practices. Educators' own survey
      responses were compared with Form-2728 reports for patients at each corresponding
      center. The association of quantity of transplant education practices used with
      wait-listing rates across dialysis centers was examined using multivariable
      negative binomial regression. RESULTS: According to Form-2728, 77% of patients
      (n=1203) were informed of their transplant options within 45 days. Educators, who
      reported low levels of transplant knowledge themselves (six of 12 questions
      answered correctly), most commonly reported giving oral recommendations to begin
      transplant evaluation (988 informed patients educated, 81% of centers) and
      referrals to external transplant education programs (959 informed patients
      educated, 81% of centers). Only 18% reported having detailed discussions about
      transplant with their patients. Compared with others, centers that used more than
      three educational activities (incident rate ratio, 1.36; 95% confidence interval,
      1.07 to 1.73) had higher transplant wait-listing rates. CONCLUSIONS: While most
      educators inform new patients that transplant is an option, dialysis centers with
      higher wait-listing rates use multiple transplant education strategies.

PMID- 26292698
TI  - The impact of pain control on physical and psychiatric functions of cancer
      patients: a nation-wide survey in Taiwan.
AB  - OBJECTIVE: To investigate the prevalence of pain in cancer patients at different
      disease statuses, the impact of pain on physical and psychiatric functions of
      patients and the satisfaction of pain control of patients at outpatient clinic
      department in Taiwan. METHODS: Short form of the Brief Pain Inventory was used as
      the outcome questionnaire. Unselected patients of different cancers and different
      disease statuses at outpatient clinic department were included. The impacts of
      their current pain control on physical function, psychiatric function and the
      satisfaction of doctors were evaluated. Logistic regression analyses were
      performed to evaluate whether the interference scale performed identically in the
      different analgesic ladders. The dependent variables were satisfaction toward
      physician and treatment. RESULTS: A total of 14 sites enrolled 2075 patients in
      the study. One thousand and fifty-one patients reported pain within the last 1
      week. In patients whose diseases deteriorated, >60% of them need analgesics for
      pain control. Pain influenced physical and psychiatric functions of patients,
      especially in the deteriorated status. More than 80% of patients were satisfied
      about current pain control, satisfaction rate related to disease status, pain
      intensities and treatments for pain. CONCLUSION: Our study found that different
      cancers at different statuses had pain at variable severity. Pain can influence
      physical and psychological functions significantly. More than 75% of subjects
      reported satisfaction over physician and pain management in outpatient clinic
      department patients with cancer pain in Taiwan.

PMID- 26292699
TI  - External validation and comparison of two nomograms predicting the probability of
      Gleason sum upgrading between biopsy and radical prostatectomy pathology in two
      patient populations: a retrospective cohort study.
AB  - The aim of this study is to validate and compare the predictive accuracy of two
      nomograms predicting the probability of Gleason sum upgrading between biopsy and
      radical prostatectomy pathology among representative patients with prostate
      cancer. We previously developed a nomogram, as did Chun et al. In this validation
      study, patients originated from two centers: Toho University Sakura Medical
      Center (n = 214) and Chibaken Saiseikai Narashino Hospital (n = 216). We assessed
      predictive accuracy using area under the curve values and constructed calibration
      plots to grasp the tendency for each institution. Both nomograms showed a high
      predictive accuracy in each institution, although the constructed calibration
      plots of the two nomograms underestimated the actual probability in Toho
      University Sakura Medical Center. Clinicians need to use calibration plots for
      each institution to correctly understand the tendency of each nomogram for their
      patients, even if each nomogram has a good predictive accuracy.

PMID- 26292700
TI  - Smokers in Brazil: who are they?
AB  - BACKGROUND: Brazil has experienced a large decline in smoking prevalence due to
      several tobacco control policies that were implemented in the past 25 years.
      Previous population-wide studies found a consistent reduction over time in daily
      cigarette consumption among all socioeconomic groups. OBJECTIVE: To examine
      changes between 2008 and 2013 in tobacco behaviours and health-related conditions
      of smokers. METHODS: We used data obtained from two nationally-representative
      surveys conducted in 2008 and 2013 to estimate the prevalence of self-reported
      psychological and physical morbidity, and nicotine dependence markers, stratified
      by gender and sociodemographic groups. Generalised linear models were used to
      understand whether absolute differences in prevalence rates over time differed by
      categories of selected variables. RESULTS: For both genders, as smoking
      prevalence declined in Brazil, there has been an increase in the proportion of
      ever smokers who have quit. In addition, remaining smokers seem to be making more
      quitting attempts. Among men with low educational level or younger than 25 years
      old, as compared to their counterparts, cessation rate showed an even greater
      increase over time. Moreover, the proportion of light smokers, which represent
      the vast majority of smokers, did not decrease. The percentage of poor health
      conditions among remaining smokers nevertheless increased, particularly among
      women, which can make future cessation more challenging. CONCLUSIONS: In Brazil,
      quitting rate is increasing, thus suggesting that tobacco control interventions
      implemented in Brazil in the past years seem to be effectively reaching the
      smoking population. This is strong evidence against the 'hardening hypothesis',
      which posits that remaining smokers decrease their willingness and ability to
      quit.

PMID- 26292701
TI  - Tobacco companies' efforts to undermine ingredient disclosure: the Massachusetts
      benchmark study.
AB  - OBJECTIVES: To assess the 'Massachusetts Benchmark Study' (MBS) that the tobacco
      companies presented to the Massachusetts Department of Public Health (MDPH) in
      1999 in response to ingredient disclosure regulations in the state. This case
      study can inform future ingredient disclosure regulations, including
      implementation of Articles 9 and 10 of the WHO Framework Convention on Tobacco
      Control (FCTC). METHODS: We analysed documents available at
      http://legacy.library.ucsf.edu to identify internal communications regarding the
      design and execution of the MBS and internal studies on the relationship between
      tar, nicotine and carbon monoxide and smoke constituents and reviewed
      publications that further evaluated data published as part of the MBS. RESULTS:
      The companies conducted extensive studies of cigarette design factors and
      ingredients that significantly impacted the levels of constituents. While this
      study asserted that by-brand emissions could be estimated reliably from published
      tar, nicotine, and carbon monoxide levels, the tobacco companies were well aware
      that factors beyond tar, nicotine and carbon monoxide influenced levels of
      constituents included in the study. This severely limited the potential
      usefulness of the MBS predictor equations. CONCLUSIONS: Despite promises to
      provide data that would allow regulators to predict constituent data for all
      brands on the market, the final MBS results offered no useful predictive
      information to inform regulators, the scientific community or consumers. When
      implementing FCTC Articles 9 and 10, regulatory agencies should demand detailed
      by-brand information on tobacco product constituents and toxin deliveries to
      users.

PMID- 26292702
TI  - The impact of tobacco expenditures on spending within Turkish households.
AB  - PURPOSE: The aim of this study is to determine whether tobacco spending has a
      'crowding out' effect on food and utility spending within Turkish households. It
      also examines whether tobacco control policies have caused the spending patterns
      of smoking households to become similar to those of non-smoking households.
      METHODS: Using 2007 and 2011 Turkish Household Budget Surveys, we estimated the
      Quadratic Conditional Engel Curve (QCEC) to determine household spending
      patterns. The QCEC was estimated using the Three-Stage Least Square (3SLS) method
      with instrumental variables. RESULTS: In Turkey, smoking households spend nearly
      8% of their monthly budgets on smoking, while the expenditures of non-smoking
      households on food, utilities and housing average 9% more than those of smoking
      households. For both years studied, a crowding out effect was demonstrated
      whereby smoking expenditure results in decreased household expenditure on food,
      housing, durable/non-durable goods and education. CONCLUSIONS: In Turkey,
      households including at least one smoker spend nearly 8% of their monthly budget
      on tobacco, with a converse reduction in spending on food and utilities. While
      tobacco control policies (eg, increasing taxes on tobacco products and extending
      smoking bans) have decreased tobacco consumption, these policies have had limited
      impact on the spending patterns of smoking households.

PMID- 26292703
TI  - Implementation of integrated care for diabetes mellitus type 2 by two Dutch care
      groups: a case study.
AB  - BACKGROUND: Even though previous research has demonstrated improved outcomes of
      integrated care initiatives, it is not clear why and when integrated care works.
      This study aims to contribute to filling this knowledge gap by examining the
      implementation of integrated care for type 2 diabetes by two Dutch care groups.
      METHODS: An embedded single case study was conducted including 26 interviews with
      management staff, care purchasers and health professionals. The Context +
      Mechanism = Outcome Model was used to study the relationship between context
      factors, mechanisms and outcomes. Dutch integrated care involves care groups,
      bundled payments, patient involvement, health professional cooperation and task
      substitution, evidence-based care protocols and a shared clinical information
      system. Community involvement is not (yet) part of Dutch integrated care.
      RESULTS: Barriers to the implementation of integrated care included insufficient
      integration between the patient databases, decreased earnings for some health
      professionals, patients' insufficient medical and policy-making expertise,
      resistance by general practitioner assistants due to perceived competition, too
      much care provided by practice nurses instead of general practitioners and the
      funding system incentivising the provision of care exactly as described in the
      care protocols. Facilitators included performance monitoring via the care chain
      information system, increased earnings for some health professionals, increased
      focus on self-management, innovators in primary and secondary care, diabetes
      nurses acting as integrators and financial incentives for guideline adherence.
      Economic and political context and health IT-related barriers were discussed as
      the most problematic areas of integrated care implementation. The implementation
      of integrated care led to improved communication and cooperation but also to
      insufficient and unnecessary care provision and deteriorated preconditions for
      person-centred care. CONCLUSIONS: Dutch integrated diabetes care is still a work
      in progress, in the academic and the practice setting. This makes it difficult to
      establish whether overall quality of care has improved. Future efforts should
      focus on areas that this study found to be problematic or to not have received
      enough attention yet. Increased efforts are needed to improve the
      interoperability of the patient databases and to keep the negative consequences
      of the bundled payment system in check. Moreover, patient and community
      involvement should be incorporated.

PMID- 26292704
TI  - Crystal structure of the metazoan Nup62*Nup58*Nup54 nucleoporin complex.
AB  - Nuclear pore complexes (NPCs) conduct nucleocytoplasmic transport and gain
      transport selectivity through nucleoporin FG domains. Here, we report a
      structural analysis of the FG Nup62*58*54 complex, which is a crucial component
      of the transport system. It comprises a ~13 nanometer-long trimerization
      interface with an unusual 2W3F coil, a canonical heterotrimeric coiled coil, and
      a kink that enforces a compact six-helix bundle. Nup54 also contains a ferredoxin
      like domain. We further identified a heterotrimeric Nup93-binding module for NPC
      anchorage. The quaternary structure alternations in the Nup62 complex, which were
      previously proposed to trigger a general gating of the NPC, are incompatible with
      the trimer structure. We suggest that the highly elongated Nup62 complex projects
      barrier-forming FG repeats far into the central NPC channel, supporting a barrier
      that guards the entire cross section. 

PMID- 26292705
TI  - Structural basis of pre-mRNA splicing.
AB  - Splicing of precursor messenger RNA is performed by the spliceosome. In the
      cryogenic electron microscopy structure of the yeast spliceosome, U5 small
      nuclear ribonucleoprotein acts as a central scaffold onto which U6 and U2 small
      nuclear RNAs (snRNAs) are intertwined to form a catalytic center next to Loop I
      of U5 snRNA. Magnesium ions are coordinated by conserved nucleotides in U6 snRNA.
      The intron lariat is held in place through base-pairing interactions with both U2
      and U6 snRNAs, leaving the variable-length middle portion on the solvent
      accessible surface of the catalytic center. The protein components of the
      spliceosome anchor both 5' and 3' ends of the U2 and U6 snRNAs away from the
      active site, direct the RNA sequences, and allow sufficient flexibility between
      the ends and the catalytic center. Thus, the spliceosome is in essence a protein
      directed ribozyme, with the protein components essential for the delivery of
      critical RNA molecules into close proximity of one another at the right time for
      the splicing reaction. 

PMID- 26292706
TI  - Covalent organic frameworks comprising cobalt porphyrins for catalytic CO2
      reduction in water.
AB  - Conversion of carbon dioxide (CO2) to carbon monoxide (CO) and other value-added
      carbon products is an important challenge for clean energy research. Here we
      report modular optimization of covalent organic frameworks (COFs), in which the
      building units are cobalt porphyrin catalysts linked by organic struts through
      imine bonds, to prepare a catalytic material for aqueous electrochemical
      reduction of CO2 to CO. The catalysts exhibit high Faradaic efficiency (90%) and
      turnover numbers (up to 290,000, with initial turnover frequency of 9400 hour(
      1)) at pH 7 with an overpotential of -0.55 volts, equivalent to a 26-fold
      improvement in activity compared with the molecular cobalt complex, with no
      degradation over 24 hours. X-ray absorption data reveal the influence of the COF
      environment on the electronic structure of the catalytic cobalt centers. 

PMID- 26292707
TI  - Structure of a yeast spliceosome at 3.6-angstrom resolution.
AB  - Splicing of precursor messenger RNA (pre-mRNA) in yeast is executed by the
      spliceosome, which consists of five small nuclear ribonucleoproteins (snRNPs),
      NTC (nineteen complex), NTC-related proteins (NTR), and a number of associated
      enzymes and cofactors. Here, we report the three-dimensional structure of a
      Schizosaccharomyces pombe spliceosome at 3.6-angstrom resolution, revealed by
      means of single-particle cryogenic electron microscopy. This spliceosome contains
      U2 and U5 snRNPs, NTC, NTR, U6 small nuclear RNA, and an RNA intron lariat. The
      atomic model includes 10,574 amino acids from 37 proteins and four RNA molecules,
      with a combined molecular mass of approximately 1.3 megadaltons. Spp42 (Prp8 in
      Saccharomyces cerevisiae), the key protein component of the U5 snRNP, forms a
      central scaffold and anchors the catalytic center. Both the morphology and the
      placement of protein components appear to have evolved to facilitate the dynamic
      process of pre-mRNA splicing. Our near-atomic-resolution structure of a central
      spliceosome provides a molecular framework for mechanistic understanding of pre
      mRNA splicing. 

PMID- 26292708
TI  - Comparative study of the efficacy of topical steroid and antibiotic combination
      therapy versus oral antibiotic alone when treating acute rhinosinusitis.

PMID- 26292709
TI  - BRACAnalysis CDx as a companion diagnostic tool for Lynparza.
AB  - Lynparza and its companion diagnostic test, BRACAnalysis were approved by the US
      FDA in December 2014 for recurrent ovarian cancer in women with a germline BRCA
      mutation. Women with a deleterious BRCA mutation are predisposed to ovarian
      cancer due to deficient homologous recombination repair. Inhibition of the PARP
      enzyme forces use of an alternate error-prone pathway for repair; PARP trapping
      is another mechanism utilized that blocks cellular replication by trapping
      inactivated PARP onto single-stranded DNA breaks. Although many companion
      diagnostic kits are already in use in oncology, BRACAnaylsis is unique in several
      ways including comprehensive BRCA gene germline profiling, availability to all
      women with ovarian cancer and implications for family members. 

PMID- 26292710
TI  - MLN4924 therapy as a novel approach in cancer treatment modalities.
AB  - MLN4924 is an investigational and a newly discovered small molecule that is a
      potent and selective inhibitor of the NEDD8 (Neural precursor cell-Expressed
      Developmentally down-regulated 8) Activating Enzyme (NAE), a pivotal regulator of
      the Cullin Ring Ligases E3 (CRL), which has been implicated recently in DNA
      damage. MLN4924 effectively inhibits tumour cell growth by inducing all three
      common types of death, namely apoptosis, autophagy and senescence and it was also
      reported that the formation of capillary vessels was significantly suppressed by
      MLN4924.In this review, we are going to highlight the molecular mechanism of
      MLN4924 in cancer therapy and its pros and cons in cancer therapy. 

PMID- 26292711
TI  - Survival trends in T cell prolymphocytic leukemia: A SEER database analysis.

PMID- 26292712
TI  - Fluorescent nanoparticles for the accurate detection of drug delivery.
AB  - INTRODUCTION: The application of intravenously administered nanoparticle (NP)
      therapies is increasingly being explored for a variety of diseases. The key to
      their success lies in a thorough understanding of nanoparticle pharmacological
      behavior, specificity and elimination kinetics. Fluorescent imaging techniques
      provide exciting opportunities to gain insight into such NP behavior in complex
      biological systems, at macroscopic as well as microscopic levels. AREAS COVERED:
      In this review, we will summarize NP labeling methods in relation to their
      established and emerging fluorescent imaging modalities for in vitro, in vivo,
      and ex vivo studies of NP behavior. We will highlight novel applications and
      discuss recent developments in techniques such as fluorescence molecular
      tomography (FMT), Forster resonance energy transfer (FRET), and Raman imaging.
      Finally, we will provide a perspective on the challenges and future directions of
      NP-based fluorescent labeling and imaging in nanotherapeutics. EXPERT OPINION:
      Commonly used in preclinical applications, fluorescent imaging of NPs can be
      achieved with minimal invasiveness and low toxicity in a multiplex fashion.
      Increasingly applied in the study of NP biodistribution, dissociation, and
      elimination behavior, fluorescent imaging allows fluid longitudinal tracking and
      visualization of NP interactions at the level of the whole animal, target
      organs/tissues, and individual cells.

PMID- 26292713
TI  - Thermal stability and unfolding pathways of hyperthermophilic and mesophilic
      periplasmic binding proteins studied by molecular dynamics simulation.
AB  - The ribose binding protein (RBP), a sugar-binding periplasmic protein, is
      involved in the transport and signaling processes in both prokaryotes and
      eukaryotes. Although several cellular and structural studies have been reported,
      a description of the thermostability of RBP at the molecular level remains
      elusive. Focused on the hyperthermophilic Thermoytoga maritima RBP (tmRBP) and
      mesophilic Escherichia coli homolog (ecRBP), we applied molecular dynamics
      simulations at four different temperatures (300, 380, 450, and 500 K) to obtain a
      deeper insight into the structural features responsible for the reduced
      thermostability of the ecRBP. The simulations results indicate that there are
      distinct structural differences in the unfolding pathway between the two homologs
      and the ecRBP unfolds faster than the hyperthermophilic homologs at certain
      temperatures in accordance with the lower thermal stability found experimentally.
      Essential dynamics analysis uncovers that the essential subspaces of ecRBP and
      tmRBP are non-overlapping and these two proteins show different directions of
      motion within the simulations trajectories. Such an understanding is required for
      designing efficient proteins with characteristics for a particular application. 

PMID- 26292714
TI  - Regular consumption of fresh orange juice increases human skin carotenoid
      content.
AB  - Dermal carotenoids are a good indicator of antioxidant status in the body. This
      study aimed to determine whether regular consumption of orange juice could
      increase dermal carotenoids. Two types of orange juice, obtained from regularly
      (CI) and partially (PRD) irrigated trees, were tested to reveal any possible
      association between juice and dermal carotenoids. Soluble solids, titratable
      acidity, and total carotenoids were quantified in the juice; skin carotenoid
      score (SCS) was assessed by Raman spectroscopy. Carotenoid content was 7.3%
      higher in PRD than in CI juice, inducing no difference in SCS. In a first trial
      with daily juice intakes for 25 days, SCS increased linearly (10%) in the
      individual with higher initial SCS, and exponentially (15%) in the individual
      with lower initial SCS. In a second trial, SCS showed a 6.5% increase after 18
      days of drinking juice every other day, but returned to initial values three days
      after last intake. Skin carotenoids can be increased by regular consumption of
      fresh orange juice, while their persistence may depend on the accumulation level,
      environmental conditions or living habits. 

PMID- 26292715
TI  - Ambivalence about supervised injection facilities among community stakeholders.
AB  - BACKGROUND: Community stakeholders express a range of opinions about supervised
      injection facilities (SIFs). We sought to identify reasons for ambivalence about
      SIFs amongst community stakeholders in two Canadian cities. FINDINGS: We used
      purposive sampling methods to recruit various stakeholder representatives (n =
      141) for key informant interviews or focus group discussions. Data were analyzed
      using a thematic process. We identified seven reasons for ambivalence about SIFs:
      lack of personal knowledge of evidence about SIFs; concern that SIF goals are too
      narrow and the need for a comprehensive response to drug use; uncertainty that
      the community drug problem is large enough to warrant a SIF(s); the need to know
      more about the "right" places to locate a SIF(s) to avoid damaging communities or
      businesses; worry that a SIF(s) will renew problems that existed prior to
      gentrification; concern that resources for drug use prevention and treatment
      efforts will be diverted to pay for a SIF(s); and concern that SIF implementation
      must include evaluation, community consultation, and an explicit commitment to
      discontinue a SIF(s) in the event of adverse outcomes. CONCLUSIONS: Stakeholders
      desire evidence about potential SIF impacts relevant to local contexts and that
      addresses perceived potential harms. Stakeholders would also like to see SIFs
      situated within a comprehensive response to drug use. Future research should
      determine the relative importance of these concerns and optimal approaches to
      address them to help guide decision-making about SIFs.

PMID- 26292716
TI  - Dose distribution and tumor control probability in out-of-field lymph node
      stations in intensity modulated radiotherapy (IMRT) vs 3D-conformal radiotherapy
      (3D-CRT) of non-small-cell lung cancer: an in silico analysis.
AB  - BACKGROUND: The advent of IMRT and image-guided radiotherapy (IGRT) in
      combination with involved-field radiotherapy (IF-RT) in inoperable non-small-cell
      lung cancer results in a decreased incidental dose deposition in elective nodal
      stations. While incidental nodal irradiation is considered a relevant by-product
      of 3D-CRT to control microscopic disease this planning study analyzed the impact
      of IMRT on dosimetric parameters and tumor control probabilities (TCP) in
      elective nodal stations in direct comparison with 3D-CRT. METHODS AND MATERIALS:
      The retrospective planning study was performed on 41 patients with NSCLC (stages
      II-III). The CTV was defined as the primary tumor (GTV + 3 mm) and all FDG-PET
      positive lymph node stations. As to the PTV (CTV + 7 mm), both an IMRT plan and a
      3D-CRT plan were established. Plans were escalated until the pre-defined dose
      constraints of normal tissues (spinal cord, lung, esophagus and heart) were
      reached. Additionally, IMRT plans were normalized to the total dose of the
      corresponding 3D-CRT. For two groups of out-of-field mediastinal node stations
      (all lymph node stations not included in the CTV (LNall_el) and those directly
      adjacent to the CTV (LNadj_el)) the equivalent uniform dose (EUD) and the TCP
      (for microscopic disease a D50 of 36.5 Gy was assumed) for the treatment with
      IMRT vs 3D-CRT were calculated. RESULTS: In comparison, a significantly higher
      total dose for the PTV could be achieved with the IMRT planning as opposed to
      conventional 3D-CRT planning (74.3 Gy vs 70.1 Gy; p = 0.03). In identical total
      reference doses, the EUD of LNadj_el is significantly lower with IMRT than with
      3D-CRT (40.4 Gy vs. 44.2 Gy. P = 0.05) and a significant reduction of TCP with
      IMRT vs 3D-CRT was demonstrated for LNall_el and LNadj_el (12.6% vs. 14.8%; and
      23.6% vs 27.3%, respectively). CONCLUSIONS: In comparison with 3D-CRT, IMRT comes
      along with a decreased EUD in out-of-field lymph node stations. This translates
      into a statistically significant decrease in TCP-values. Yet, the combination of
      IF-RT and IMRT leads to a significantly better sparing of normal tissues and
      higher total doses whereas the potential therapeutic drawback of decreased
      incidental irradiation of elective lymph nodes is moderate.

PMID- 26292717
TI  - Real-time analysis of epithelial-mesenchymal transition using fluorescent single
      domain antibodies.
AB  - Vimentin has become an important biomarker for epithelial-mesenchymal transition
      (EMT), a highly dynamic cellular process involved in the initiation of metastasis
      and cancer progression. To date there is no approach available to study
      endogenous vimentin in a physiological context. Here, we describe the selection
      and targeted modification of novel single-domain antibodies, so-called
      nanobodies, to trace vimentin in various cellular assays. Most importantly, we
      generated vimentin chromobodies by combining the binding moieties of the
      nanobodies with fluorescent proteins. Following chromobody fluorescence in a
      cancer-relevant cellular model, we were able for the first time to monitor and
      quantify dynamic changes of endogenous vimentin upon siRNA-mediated knockdown,
      induction with TGF-beta and modification with Withaferin A by high-content
      imaging. This versatile approach allows detailed studies of the spatiotemporal
      organization of vimentin in living cells. It enables the identification of
      vimentin-modulating compounds, thereby providing the basis to screen for novel
      therapeutics affecting EMT. 

PMID- 26292718
TI  - Association of maternal anemia with other risk factors in occurrence of Great
      obstetrical syndromes at university clinics, Kinshasa, DR Congo.
AB  - BACKGROUND: Maternal anemia, a common situation in developing countries, provokes
      impairment of nutrients/oxygen supply to the placenta-fetus unit that leads to
      Great obstetrical syndromes (GOS). In our setting, however, occurrence of GOS has
      been found also depending on variables existing prior to pregnancy such as
      diabetes in family, hypertension in family, previous macrosomia, stillbirth, SGA
      and pre-eclampsia as well as overweight/obesity. Our study thus aimed to
      determine the magnitude of maternal anemia and its association with these pre
      pregnancy high-risk variables in occurrence of GOS. METHODS: This is a cross
      sectional study including women delivered at the University Clinics of Kinshasa,
      DR Congo, 12. during 18 months. Anemia was stated at hemoglobin blood
      concentration < 10 g/dL. Sampled women were checked for pregnancy high-risk
      factors and pregnancy complications. Odds ratios (95% confidence intervals) were
      calculated to establish associations of anemia with various variables.
      Multivariate calculations aimed to isolate variables influencing these
      associations. The p <0.05 was considered significant. RESULTS: The study sample
      included 412 women, among whom 220 (53.4%) were diagnosed anemic. Anemia was
      found significantly linked to malaria, urinary infection, cesarean section,
      prematurity, SGA and stillbirth whose risk was 1.6 - 6.1 times augmented. Anemia
      was also found linked to pre-pregnancy high-risk factors such as age < 18 and >=
      35 years, previous miscarriage, grand multiparity, diabetes in family, previous
      prematurity, overweight/obesity, previous cesarean section and previous pre
      eclampsia, all of them enhancing the link of maternal anemia with complications.
      CONCLUSION: Maternal anemia is very prevalent among pregnant women of our
      setting. It strongly contributes to worsening of morbidities that act with
      pregnancy high-risk factors in raising the risk of cesarean section, prematurity,
      SGA and stillbirth.

PMID- 26292719
TI  - Graphite-Conjugated Pyrazines as Molecularly Tunable Heterogeneous
      Electrocatalysts.
AB  - Condensation of ortho-phenylenediamine derivatives with ortho-quinone moieties at
      edge planes of graphitic carbon generates graphite-conjugated pyrazines (GCPs)
      that are active for oxygen reduction electrocatalysis in alkaline aqueous
      electrolyte. Catalytic rates of oxygen reduction are positively correlated with
      the electrophilicity of the active site pyrazine unit and can be tuned by over 70
      fold by appending electron-withdrawing substituents to the phenylenediamine
      precursors. Discrete molecular analogs containing pyrazine moieties display no
      activity above background under identical conditions. This simple bottom up
      method for constructing molecularly well-defined active sites on ubiquitous
      graphitic solids enables the rational design of tunable heterogeneous catalysts. 

PMID- 26292720
TI  - Transcutaneous auricular vagus nerve stimulation for pediatric epilepsy: study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: Recently, clinical observations reported the potential benefit of
      vagus nerve stimulation (VNS) for pediatric epilepsy. Transcutaneous auricular
      vagus nerve stimulation (ta-VNS) is a newer non-invasive VNS, making it more
      accessible for treating pediatric epilepsy, yet there is limited clinical
      evidence for its effectiveness. METHODS/DESIGN: A three-center, randomized,
      parallel, controlled trial will be carried out to evaluate whether ta-VNS
      improves pediatric epilepsy. Pediatric patients aged 2 to 14 years with epilepsy
      will be recruited and randomly assigned to transcutaneous auricular vagus nerve
      stimulation (ta-VNS) group, transcutaneous auricular non-vagus nerve stimulation
      (tan-VNS) group, and control group with a 1:1: sqrt(2) allocation, as per a
      computer generated randomization schedule stratified by study center using
      permuted blocks of random sizes. We will use Zelen's design, in which
      randomization occurs before informed consent. Patients in the stimulation groups
      will receive tan-VNS or ta-VNS three times a day for 6 months. Patients in the
      control group will not be provided with any stimulation during the 6 months. The
      guardians of the patients are required to keep a detailed diary to record the
      data. Outcome assessment including seizure frequency, electroencephalogram (EEG),
      heart rate variability (HRV) analysis, quality of life (QOL) and adverse events
      will be made at baseline and 2, 4 and 6 months after ta-VNS initiation. The
      seizure frequency and adverse events will be followed up at 1 year and 1.5 years
      after ta-VNS initiation. DISCUSSION: Results of this trial will help clarify
      whether ta-VNS treatment is beneficial for pediatric patients, and will make
      clear whether the anticonvulsive effect of ta-VNS is correlated with the
      improvement of sympathovagal imbalance. TRIAL REGISTRATION:  CLINICAL TRIALS
      IDENTIFIER: NCT02004340 . Registration date: 13 November 2013.

PMID- 26292721
TI  - Design and rationale of the IN CONTROL trial: the effects of real-time continuous
      glucose monitoring on glycemia and quality of life in patients with type 1
      diabetes mellitus and impaired awareness of hypoglycemia.
AB  - BACKGROUND: Hypoglycemia is the main side effect of intensified insulin therapy
      in type 1 diabetes and recognized as a limitation in achieving glycemic targets.
      Patients with impaired awareness of hypoglycemia have a threefold to sixfold
      increased risk of severe hypoglycemia. Real-time continuous glucose monitoring
      may help patients with type 1 diabetes to achieve better glycemic control with
      less hypoglycemic episodes. Accordingly, one may hypothesize that particularly
      type 1 diabetes mellitus patients with impaired awareness of hypoglycemia will
      profit most from this technology with improvements in their quality of life.
      However, this has not yet been established. This trial aims to study the effect
      of real-time continuous glucose monitoring on glycemia and quality of life
      specifically in type 1 diabetes mellitus patients with established impaired
      awareness of hypoglycemia. METHODS/DESIGN: This is a two-center, randomized,
      cross-over trial with a 12-week wash-out period in between intervention periods.
      A total of 52 type 1 diabetes mellitus patients with impaired awareness of
      hypoglycemia according to Gold et al. criteria will be randomized to receive real
      time continuous glucose monitoring or blinded continuous glucose monitoring for
      16 weeks. After a wash-out period, patients will cross over to the other
      intervention. The primary outcome measure is time spent in euglycemia. Secondary
      outcomes include (diabetes-specific) markers of quality of life and other
      glycemic variables. DISCUSSION: It remains unclear whether patients with type 1
      diabetes and impaired awareness of hypoglycemia benefit from real-time continuous
      glucose monitoring in real-life. This study will provide insight into the
      potential benefits of real-time continuous glucose monitoring in this patient
      population. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01787903.

PMID- 26292722
TI  - Inhibition of glycogen synthase kinase-3 beta induces apoptosis and mitotic
      catastrophe by disrupting centrosome regulation in cancer cells.
AB  - Glycogen synthase kinase-3 beta (GSK-3beta) has been investigated as a
      therapeutic target for numerous human diseases including cancer because of their
      diverse cellular functions. Although GSK-3beta inhibitors have been investigated
      as anticancer reagents, precise biological mechanisms remain to be determined. In
      this study, we investigated the anticancer effects of GSK-3beta inhibitors on
      cancer cell lines and observed centrosome dysregulation which resulted in
      abnormal mitosis. Mitotic checkpoints sensed the mitotic abnormalities and
      induced apoptosis. For cells that were inherently resistant to apoptosis, cell
      death distinct from apoptosis was induced. After GSK-3beta inhibitor treatment,
      these cells exhibited characteristic features of mitotic catastrophe, including
      distended and multivesiculated nuclei and inappropriate reductions in cyclin B1
      expression. This suggested that mitotic catastrophe was an alternative mechanism
      in cells resistant to apoptosis. Although the role of GSK-3beta in centrosomes
      has not yet been clarified, phosphorylated GSK-3beta was localised in
      centrosomes. From these data, GSK-3beta seems to regulate centrosome function.
      Thus, we propose that centrosome dysregulation is an important mechanism for the
      anticancer effects of GSK-3beta inhibitors and that mitotic catastrophe serves as
      a safe-guard system to remove cells with any mitotic abnormalities induced by GSK
      3beta inhibition. 

PMID- 26292724
TI  - Tandem mass spectrometry and infrared spectroscopy as a tool to identify peptide
      oxidized residues.
AB  - The final products obtained by the oxidation of small model peptides containing
      the thioether function, either methionine or S-methyl cysteine, have been
      characterized by tandem mass spectrometry and IR Multiple Photon Dissociation
      (IRMPD) spectroscopy. The modified positions have been clearly identified by the
      CID-MS(2) fragmentation mass spectra with or without loss of sulfenic acid, as
      well as by the vibrational signature of the sulfoxide bond at around 1000 cm(-1).
      The oxidation of the thioether function did not lead to the same products in
      these model peptides. The sulfoxide and sulfone (to a lesser extent) have been
      clearly identified as final products of the oxidation of S-methyl-glutathione (GS
      Me). Decarboxylation or hydrogen loss are the major oxidation pathways in GS-Me,
      while they have not been observed in tryptophan-methionine and methionine
      tryptophan (Trp-Met and Met-Trp). Interestingly, tryptophan is oxidized in the
      dipeptide Met-Trp, while that is not the case in the reverse sequence (Trp-Met). 

PMID- 26292723
TI  - Targeting BTK for the treatment of FLT3-ITD mutated acute myeloid leukemia.
AB  - Approximately 20% of patients with acute myeloid leukaemia (AML) have a mutation
      in FMS-like-tyrosine-kinase-3 (FLT3). FLT3 is a trans-membrane receptor with a
      tyrosine kinase domain which, when activated, initiates a cascade of
      phosphorylated proteins including the SRC family of kinases. Recently our group
      and others have shown that pharmacologic inhibition and genetic knockdown of
      Bruton's tyrosine kinase (BTK) blocks AML blast proliferation, leukaemic cell
      adhesion to bone marrow stromal cells as well as migration of AML blasts. The
      anti-proliferative effects of BTK inhibition in human AML are mediated via
      inhibition of downstream NF-kappaB pro-survival signalling however the upstream
      drivers of BTK activation in human AML have yet to be fully characterised. Here
      we place the FLT3-ITD upstream of BTK in AML and show that the BTK inhibitor
      ibrutinib inhibits the survival and proliferation of FLT3-ITD primary AML blasts
      and AML cell lines. Furthermore ibrutinib inhibits the activation of downstream
      kinases including MAPK, AKT and STAT5. In addition we show that BTK RNAi inhibits
      proliferation of FLT3-ITD AML cells. Finally we report that ibrutinib reverses
      the cyto-protective role of BMSC on FLT3-ITD AML survival. These results argue
      for the evaluation of ibrutinib in patients with FLT3-ITD mutated AML. 

PMID- 26292725
TI  - Apigenin induces autophagic cell death in human papillary thyroid carcinoma BCPAP
      cells.
AB  - Apigenin, abundantly present in fruits and vegetables, is recognized as a
      flavonoid with anti-inflammatory, antioxidant and anticancer properties. In this
      study, we first investigated the anti-neoplastic effects of apigenin on papillary
      thyroid carcinoma (PTC) cell line BCPAP cells. Our results show that apigenin
      inhibited the viability of BCPAP cells in a dose-dependent manner. A large body
      of evidence demonstrates that autophagy contributes to cell death in certain
      contexts. In the present study, autophagy was induced by apigenin treatment in
      BCPAP cells, as evidenced by Beclin-1 accumulation, conversion of LC3 protein,
      p62 degradation as well as the significantly increased formation of acidic
      vesicular organelles (AVOs) compared to the control group. 3-MA, an autophagy
      inhibitor, rescued the cells from apigenin-induced cell death. Notably, apigenin
      enhanced production of reactive oxygen species (ROS), and subsequent induction of
      significant DNA damage as monitored by the TUNEL assay. In addition, apigenin
      treatment caused a significant accumulation of cells in the G2/M phase via down
      regulation of Cdc25C expression. Our findings reveal that apigenin inhibits
      papillary thyroid cancer cell viability by the stimulation of reactive oxygen
      species (ROS) production, induction of DNA damage, leading to G2/M cell cycle
      arrest followed by autophagic cell death. Thus, our results provide new insights
      into the molecular mechanisms underlying apigenin-mediated autophagic cell death
      and suggest apigenin as a potential chemotherapeutic agent which is able to fight
      against papillary thyroid cancer. 

PMID- 26292726
TI  - Local coordination state of rare earth in eutectic scintillators for neutron
      detector applications.
AB  - Atomic distribution in phosphors for neutron detection has not been fully
      elucidated, although their ionization efficiency is strongly dependent on the
      state of the rare earth in the matrix. In this work, we examine optical
      properties of Eu-doped 80LiF-20CaF2 eutectics for neutron detector applications
      based on the Eu distribution. At low concentrations, aggregation of Eu cations is
      observed, whereas homogeneous atomic dispersion in the CaF2 layer, to substitute
      Ca(2+) ions, is observed in the eutectics at high concentrations. Eu LIII edge X
      ray absorption fine structure (XAFS) analysis suggests that neutron responses do
      not depend on the amount of Eu(2+) ions. However, transparency, which depends on
      an ordered lamellar structure, is found to be important for a high light yield in
      neutron detection. The results confirm the effectiveness of the basic idea
      concerning the separation of radiation absorbers and activators in particle
      radiation scintillation and present potential for further improvement of novel
      bulk detectors. 

PMID- 26292728
TI  - IWBDA 2014.

PMID- 26292727
TI  - Guided differentiation of bone marrow stromal cells on co-cultured cartilage and
      bone scaffolds.
AB  - Focal chondral defects that result from traumatic injuries to the knee remain one
      of the most common causes of disability in patients. Current solutions for
      healing focal cartilage defects are mainly limited by the production of inferior
      cartilage-like tissue and subsequent delamination due to incomplete healing of
      the subchondral bone. In this experiment a polymeric osteochondral implant for
      guiding autologous bone marrow stem cells (BMSCs) to populate the scaffold to
      create distinctive bone and cartilage tissue is used. The cartilage component
      presents bioactive aligned nanofibers containing chondroitin sulfate and
      hyaluronic acid while the bone component includes hydroxyapatite to promote
      chondrogenic and osteogenic differentiation of the rat BMSCs in vitro. The
      different cartilage and bone components resulted in the elevated expression of
      osteogenic markers such as bone sialoprotein, runt related transcription factor
      2, and bone morphogenetic protein 2 in the deeper bone layer and chondrogenic
      markers such as collagen type II and aggrecan in the cartilage layer. Through
      immunofluorescence imaging, the alignment of the secreted collagen type II
      fibrils and aggrecan was visualized and quantified on the cartilage component of
      the scaffold. These current studies show that the biodegradable biphasic
      osteochondral implant may be effective in promoting more hyaline-like tissue to
      fill in chondral defects of the knee. 

PMID- 26292731
TI  - Limiting replication stress during somatic cell reprogramming reduces genomic
      instability in induced pluripotent stem cells.
AB  - The generation of induced pluripotent stem cells (iPSC) from adult somatic cells
      is one of the most remarkable discoveries in recent decades. However, several
      works have reported evidence of genomic instability in iPSC, raising concerns on
      their biomedical use. The reasons behind the genomic instability observed in iPSC
      remain mostly unknown. Here we show that, similar to the phenomenon of oncogene
      induced replication stress, the expression of reprogramming factors induces
      replication stress. Increasing the levels of the checkpoint kinase 1 (CHK1)
      reduces reprogramming-induced replication stress and increases the efficiency of
      iPSC generation. Similarly, nucleoside supplementation during reprogramming
      reduces the load of DNA damage and genomic rearrangements on iPSC. Our data
      reveal that lowering replication stress during reprogramming, genetically or
      chemically, provides a simple strategy to reduce genomic instability on mouse and
      human iPSC. 

PMID- 26292756
TI  - Upsilon-secretase and LARG mediate distinct RGMa activities to control
      appropriate layer targeting within the optic tectum.
AB  - While a great deal of progress has been made in understanding the molecular
      mechanisms that regulate retino-tectal mapping, the determinants that target
      retinal projections to specific layers of the optic tectum remain elusive. Here
      we show that two independent RGMa-peptides, C- and N-RGMa, activate two distinct
      intracellular pathways to regulate axonal growth. C-RGMa utilizes a Leukemia
      associated RhoGEF (LARG)/Rho/Rock pathway to inhibit axonal growth. N-RGMa on the
      other hand relies on Upsilon-secretase cleavage of the intracellular portion of
      Neogenin to generate an intracellular domain (NeICD) that uses LIM-only protein 4
      (LMO4) to block growth. In the developing tectum (E18), overexpression of C-RGMa
      and dominant-negative LARG (LARG-PDZ) induced overshoots in the superficial
      tectal layer but not in deeper tectal layers. In younger embryos (E12), C-RGMa
      and LARG-PDZ prevented ectopic projections toward deeper tectal layers,
      indicating that C-RGMa may act as a barrier to descending axons. In contrast both
      N-RGMa and NeICD overexpression resulted in aberrant axonal-paths, all of which
      suggests that it is a repulsive guidance molecule. Thus, two RGMa fragments
      activate distinct pathways resulting in different axonal responses. These data
      reveal how retinal projections are targeted to the appropriate layer in their
      target tissue. 

PMID- 26292757
TI  - An essential role for Ink4 and Cip/Kip cell-cycle inhibitors in preventing
      replicative stress.
AB  - Cell-cycle inhibitors of the Ink4 and Cip/Kip families are involved in cellular
      senescence and tumor suppression. These inhibitors are individually dispensable
      for the cell cycle and inactivation of specific family members results in
      increased proliferation and enhanced susceptibility to tumor development. We have
      now analyzed the consequences of eliminating a substantial part of the cell-cycle
      inhibitory activity in the cell by generating a mouse model, which combines the
      absence of both p21(Cip1) and p27(Kip1) proteins with the endogenous expression
      of a Cdk4 R24C mutant insensitive to Ink4 inhibitors. Pairwise combination of
      Cdk4 R24C, p21-null and p27-null alleles results in frequent hyperplasias and
      tumors, mainly in cells of endocrine origin such as pituitary cells and in
      mesenchymal tissues. Interestingly, complete abrogation of p21(Cip1) and
      p27(Kip1) in Cdk4 R24C mutant mice results in a different phenotype characterized
      by perinatal death accompanied by general hypoplasia in most tissues. This
      phenotype correlates with increased replicative stress in developing tissues such
      as the nervous system and subsequent apoptotic cell death. Partial inhibition of
      Cdk4/6 rescues replicative stress signaling as well as p53 induction in the
      absence of cell-cycle inhibitors. We conclude that one of the major physiological
      activities of cell-cycle inhibitors is to prevent replicative stress during
      development. 

PMID- 26292760
TI  - An evaluation of the quality of care for women with low risk pregnanacy: The use
      of evidence-based practice during labour and childbirth in four public hospitals
      in Tehran.
AB  - OBJECTIVE: there is a consensus that the adoption of evidence-based practice
      contributes to the improvement of maternity care. Iranian National Guidelines for
      Normal Childbirth included evidence-based practice and were disseminated to
      hospitals in 2006 but little is known about the success of implementation. This
      study investigates the provision of care during labour and childbirth in
      comparison with national guidelines in four public hospitals in Tehran. DESIGN:
      this was a descriptive evaluation study and investigated the provision of care
      during labour and childbirth using current evidence-based practice as the
      indicator of quality. PARTICIPANTS AND SETTING: the observational and interview
      data were collected using checklist and interview guide based upon standards for
      evidence-based care in four public hospitals in Tehran. In 24 women who were
      admitted in normal labour, practices were observed until the end of the third
      stage of labour, to determine concordance with Iranian National Guidelines for
      Normal Childbirth. A further 100 postpartum woman were interviewed about their
      care during labour and childbirth in the early postpartum period before discharge
      from the postnatal ward. FINDINGS: beneficial and lifesaving practices such as
      assessing mothers' well-being; removal of the placenta in the third stage of
      labour, as well as skin-to-skin contact and early initiating of breast feeding
      were recorded in most cases. However, the use of practices such as routine
      augmentation and induction of labour, fundal pressure, conducting routine
      episiotomy were noted. KEY CONCLUSIONS: this evaluation study shows good practice
      and areas for improvement as practices fail to meet evidence based standards.
      Thus, there is potential for quality improvement and economic savings in Tehran
      maternity hospitals. However closing the gap between guidelines based on best
      evidence and actual clinical practice in childbirth is a challenge. Practical
      solutions to enable implementation of evidence-based guidelines for normal
      childbirth in low risk women require further studies, especially from the
      providers' perspective. IMPLICATIONS FOR PRACTICE: national programs which focus
      on organisational framework, interventions to change providers' attitudes towards
      the development of a culture of birth as a normal and physiological process are
      more likely to be important in the Iranian context. Involving professional
      midwives more in the care for normal childbirth may help to improve quality of
      care during normal labour and childbirth in terms of evidence-based practice.

PMID- 26292759
TI  - Ube2s regulates Sox2 stability and mouse ES cell maintenance.
AB  - Sox2 has a critical role in embryonic stem (ES) cell maintenance and
      differentiation. Interestingly, its activity is highly dosage-dependent. Although
      transcriptional regulation of Sox2 has been extensively studied, the mechanisms
      orchestrating its degradation remain unclear. In this study, we identified
      ubiquitin-conjugating enzyme E2S (Ube2s) as a novel effector for Sox2 protein
      degradation. Ube2s mediates K11-linked polyubiquitin chain formation at the Sox2
      K123 residue, thus marking it for proteasome-mediated degradation. Besides its
      role in fine-tuning the precise level of Sox2, Ube2s reinforces the self-renewing
      and pluripotent state of ES cells. Importantly, it also represses Sox2-mediated
      ES cell differentiation toward the neural ectodermal lineage. 

PMID- 26292761
TI  - HEALTH PROFESSIONALS' USER EXPERIENCE OF THE INTELLIGENT BED IN PATIENTS' HOMES.
AB  - BACKGROUND: The intelligent bed is a medical bed with several home healthcare
      functions. It includes, among others, an "out of bed" detector, a moisture
      detector, and a catheter bag detector. The design purpose of the intelligent bed
      is to assist patients in their daily living, facilitate the work of clinical
      staff, and improves the quality of care. The aim of this sub-study of the iCare
      project was to explore how health professionals (HPs) experience and use the
      intelligent bed in patients' homes. METHODS: The overall research design is
      inspired by case study methodology. A triangulation of data collection techniques
      has been used: log book, documentation study, participant observations (n = 45
      hr), and qualitative interviews (n = 23). The data have been analyzed by means of
      Nvivo 9.0. FINDINGS: We identified several themes: HP transformation from passive
      technology recipient to innovator; individualized care; work flow redesign; and
      sensor technology intruding on patient privacy. CONCLUSIONS: It is suggested that
      functions of the intelligent bed can result in more individualized care, workflow
      redesign, and time savings for the health professionals in caring for elderly
      patients. However, the technology intruded on patients' privacy.

PMID- 26292758
TI  - Principles of antibody-mediated TNF receptor activation.
AB  - From the beginning of research on receptors of the tumor necrosis factor (TNF)
      receptor superfamily (TNFRSF), agonistic antibodies have been used to stimulate
      TNFRSF receptors in vitro and in vivo. Indeed, CD95, one of the first cloned
      TNFRSF receptors, was solely identified as the target of cell death-inducing
      antibodies. Early on, it became evident from in vitro studies that valency and
      Fcgamma receptor (FcgammaR) binding of antibodies targeting TNFRSF receptors can
      be of crucial relevance for agonistic activity. TNFRSF receptor-specific
      antibodies of the IgM subclass and secondary cross-linked or aggregation prone
      dimeric antibodies typically display superior agonistic activity compared with
      dimeric antibodies. Likewise, anchoring of antibodies to cell surface-expressed
      FcgammaRs potentiate their ability to trigger TNFRSF receptor signaling. However,
      only recently has the relevance of oligomerization and FcgammaR binding for the
      in vivo activity of antibody-induced TNFRSF receptor activation been
      straightforwardly demonstrated in vivo. This review discusses the crucial role of
      oligomerization and/or FcgammaR binding for antibody-mediated TNFRSF receptor
      stimulation in light of current models of TNFRSF receptor activation and
      especially the overwhelming relevance of these issues for the rational
      development of therapeutic TNFRSF receptor-targeting antibodies. 

PMID- 26292763
TI  - An update on barriers to adolescent human papillomavirus vaccination in the USA.
AB  - Human papillomavirus is the most common sexually transmitted infection in the
      USA. It is the primary cause of almost all cervical cancers as well as several
      other cancers that affect both men and women. Adolescents of both genders can now
      prevent transmission of the most common oncogenic strains of human papillomavirus
      by obtaining a safe, three-dose vaccine series. However, despite its potential to
      save lives and reduce severe morbidity, many US adolescents have not been
      vaccinated. This is in contrast to other countries where high rates of
      vaccination are already reducing rates of cervical intra-epithelial neoplasia and
      genital warts. This article describes barriers recently reported among families
      in the USA and concludes with suggestions for improving uptake. 

PMID- 26292762
TI  - Primary care in Switzerland: evolution of physicians' profile and activities in
      twenty years (1993-2012).
AB  - BACKGROUND: According to the Organization for Economic Cooperation and
      Development, the Swiss healthcare system is one of the most effective in the
      world. Yet, as other occidental countries, it has to face the increase of chronic
      diseases frequency and its resulting cost, particularly for primary care (PC).
      However very few consistent data are available to describe PC features and its
      evolution over time. The aim of this study is to describe the evolution of the
      Swiss PC physicians' (PCPs) profile and activities between 1993 and 2012.
      METHODS: The date come from two independent European surveys carried out in
      Switzerland respectively in 1993 and 2012. Both surveys were cross-sectional ones
      and based on representative samples of 200 PCPs, interviewed by questionnaire.
      RESULTS: In 20 years, PCPs became older (median age 46 vs 56, p < 0.001) and more
      feminized (7 % vs 22 %, p < 0.001). Nowadays, they more often work in group
      practices (28 % vs 52 % in 2012, p < 0.001) and are more involved in other paid
      activities (28 % vs 66 % in 2012, p < 0.001). All the PCPs have a computer in
      2012 (78 % in 1993, p < 0.001) and it is mostly used for keeping records of
      consultations (47 %). The number of daily face-to-face contacts with patients
      decreased from 31 to 24 but the average length rose from 15 to 20 min (p <
      0.001). PCPs provide fewer pediatric and gynecological services but their
      activity remains globally unchanged in other domains. The frequency of meetings
      with other disciplines decreased significantly (e.g. once/month face-to-face
      meets with ambulatory specialists: 78 % vs 23 % in 2012, p < 0.001). The
      involvement of PCPs in follow-up and treatment of chronic disease globally little
      differed. In 2012, 8.5 % of the PCPs never performed any chirurgical acts (vs 0 %
      in 1993, p < 0.001). CONCLUSION: This study showed a substantial evolution of
      Swiss PC over the last twenty years in terms of socio-demographic, organizational
      and service provided. The main changes include: feminization and ageing, lower
      diversity in services provided, fewer but longer consultations. These changes may
      have important implications for patients' management and will need to be
      considered for health planning purposes.

PMID- 26292764
TI  - Therapeutic drug monitoring for either oral or intravenous busulfan when combined
      with pre- and post-transplantation cyclophosphamide.
AB  - Busulfan (Bu)/cyclophosphamide (Cy) is a standard conditioning platform for
      allogeneic transplantation. We developed a strategy separating the Cy into two
      pre/post-transplantation doses (PTCy), providing myeloablative conditioning and
      single-agent graft-versus-host disease (GVHD) prophylaxis. We investigated the
      impact of Bu route on treatment-related toxicity for 131 consecutive adult
      patients. Busulfan was administered in four daily divided doses either orally (n
      = 72) or intravenously (n = 59) with pharmacokinetics on the first-dose and as
      necessary on subsequent doses to achieve a target area-under-the-concentration
      curve (AUC) of 800-1400 MUmol*min/L per dose. BuCy/PTCy with pharmacokinetics is
      well-tolerated with low treatment-related toxicity. Hepatic veno-occlusive
      disease incidence was 6% with two fatal events. Bu administration route in the
      context of BuCy/PTCy did not statistically impact hepatotoxicity, GVHD, relapse,
      disease-free survival, or overall survival. The BuCy/PTCy platform has a low
      incidence of treatment-related toxicity, including hepatotoxicity, in hematologic
      malignancies when using pharmacokinetics for a target AUC of 800-1400
      MUmol*min/L, irrespective of Bu administration route. 

PMID- 26292766
TI  - Localization of heat shock protein 110 in canine mammary gland tumors.
AB  - Heat shock proteins (HSPs) function as molecular chaperones in the regulation of
      protein folding, conformation, and assembly; in addition, they also protect cells
      from protein-protein aggregation resulting from cellular stress. Recently, HSPs
      were shown to be overexpressed in several human cancer cells compared with normal
      cells. HSPs are considered to be related to apoptosis-associated proteins, and
      inhibition of apoptosis promotes tumor growth. Canine mammary gland tumors have
      received a great deal of attention from researchers due to the many common
      biological and histological characteristics that they share with human tumors. We
      previously confirmed that HSP110 is a canine mammary gland tumor antigen and
      reported that HSP110 mRNA expression significantly increased in tumor tissue. We
      have now created a functional recombinant canine HSP110 protein and a rabbit anti
      HSP110 polyclonal antibody. This recombinant protein can refold heat-denatured
      firefly luciferase at 42 degrees C. Immunohistochemical analysis showed that
      HSP110 was mainly localized in the cytoplasm of epithelial and interstitial cells
      in canine mammary gland tumors. Extensive genomic research has revealed genetic
      similarities between humans and dogs; comparative oncological studies between
      these species have made remarkable progress. The results reported here contribute
      valuable oncological knowledge for the development of novel therapeutic methods
      in both veterinary science and human medicine. 

PMID- 26292767
TI  - Neurofilament Accumulation in Rabbit Retinas.
AB  - An eosinophilic body (EB) was observed in the inner nuclear layer and the outer
      plexiform layer of the anterior dorsal region of the retina in New Zealand White,
      Japanese White and Dutch rabbits. Immunohistochemistry confirmed that the EB was
      an accumulation of neurofilaments (NFs). Ultrastructurally, intermediate
      filaments of approximately 10 nm in diameter were observed in the EB, but there
      were no intracellular organelles. These results suggested that the NFs had
      accumulated in the neurites of the horizontal cells in the retina. This is the
      first description of a new pattern of NF accumulation in the mammalian retina.
      The prevalence of the EBs increased significantly in 44-56-week-old male Dutch
      rabbits (38.9 %) compared with 18-23-week-old (12.9 %) rabbits, suggesting that
      the formation of EBs in the rabbit retina could be an age-related change. 

PMID- 26292768
TI  - Equine Cutaneous Mast Cell Tumours Exhibit Variable Differentiation,
      Proliferation Activity and KIT Expression.
AB  - Equine cutaneous mast cell tumours (CMCTs) are generally considered to be benign
      skin lesions, although recurrent and multicentric tumours have been described.
      For canine CMCTs, grading and prognostic approaches are well established and
      aberrant KIT expression as well as high proliferation indices are associated with
      poor outcome. However, in the case of equine CMCTs, morphological features,
      proliferative activity and KIT expression pattern have not been assessed or
      related to biological behaviour, and there is discussion as to whether CMCTs are
      true neoplastic processes. The present study describes 45 equine CMCTs in terms
      of their morphology and KIT and PCNA expression by immunohistochemistry. KIT
      expression was classified as membranous (I), cytoplasmic and focally stippled
      (II) or diffuse cytoplasmic (III). A large proportion of the tumours were
      multinodular or diffuse dermal infiltrates of mast cells with mild anisokaryosis,
      a low proliferative rate and a dominance of KIT pattern I, representing well
      differentiated CMCTs. In approximately one third of the cases, the mast cells
      exhibited more infiltrative growth, moderate to marked anisokaryosis and a higher
      degree of proliferation. These were classified as poorly differentiated CMCTs and
      exhibited only KIT patterns II and III. These findings indicate that there is a
      subgroup of poorly differentiated equine CMCTs, in which there is an association
      between aberrant KIT expression, high proliferative rate and potential aggressive
      behaviour, all features that confirm at least the poorly differentiated CMCT as a
      true neoplastic processes. 

PMID- 26292765
TI  - Large granular lymphocytes are universally increased in human, macaque, and
      feline lentiviral infection.
AB  - Large granular lymphocytes (LGLs) have only been anecdotally reported in HIV
      infection. We previously reported an LGL lymphocytosis in FIV-infected cats
      associated with a rise in FIV proviral loads and a marked neutropenia that
      persisted during chronic infection. Extensive immunophenotyping of peripheral
      blood mononuclear cells in cats chronically infected with FIV were identified
      LGLs as CD8lo(+)FAS(+); this cell population expanded commensurate with viral
      load. CD8lo(+)FAS(+) cells expressed similar levels of interferon-gamma compared
      to CD8lo(+)FAS(+) cells from FIV-naive control animals, yet CD3E expression,
      which was increased on total CD8(+) T cells in FIV-infected cats, was decreased
      on CD8lo(+)FAS(+) cells. Down-modulation of CD3 expression was reversed after
      culturing PBMC for 3 days in culture with ConA/IL-2. We identified CD8lo(+)FAS(+)
      LGLs to be polyclonal T cells lacking CD56 expression. Blood smears from HIV
      infected individuals and SIVmac239-infected rhesus macaques revealed increased
      LGLs compared to HIV/SIV negative counterparts. In humans, there was no
      correlation with viral load or treatment and in macaques the LGLs arose in acute
      SIV infection with increases in viremia. This is the first report describing and
      partially characterizing LGL lymphocytosis in association with lentiviral
      infections in three different species. 

PMID- 26292769
TI  - Benefits and Risks for People and Livestock of Keeping Companion Animals:
      Searching for a Healthy Balance.
AB  - The mission of the CALLISTO (Companion Animals multisectoriaL interprofessionaL
      Interdisciplinary Strategic Think tank On zoonoses) project was to provide an
      overview of the current situation on the role of companion animals as a source of
      infectious diseases for people and food animals. It also aimed to identify
      knowledge and technology gaps for the most important zoonoses and propose
      targeted actions to reduce the risk of zoonotic diseases transmitted via
      companion animals. After a 3-year study, its members have developed practical
      recommendations for improved data collection on companion animal numbers and the
      mechanisms for disease surveillance in companion animals. They highlight the
      importance of introducing a system for the unique identification of dogs and
      other companion animals with an implanted microchip transponder and storage of
      the details it contains on an internationally accessible online database. Their
      report also emphasises the need for balanced communication with the public on the
      risks and benefits of pet ownership and the value of the 'One Health' concept to
      encourage closer collaboration between veterinary and human medical
      professionals. 

PMID- 26292770
TI  - Mucocutaneous Inflammatory Pseudotumours in Simultaneous Mycobacterium avium
      subsp. avium and Mycobacterium avium subsp. hominissuis Infection in a Cat.
AB  - Mycobacterial spindle cell 'pseudotumour' has been described only once in cats.
      This unique proliferation of spindle-shaped histiocytes containing Mycobacterium
      avium is associated with extensive subcutaneous lesions. We report mycobacterial
      pseudotumour with invasion of muscular and subcutaneous tissues in a 1-year-old
      female domestic longhair cat. Lesions involved the facial muscles and nasal
      cavity, making surgical excision impossible. Necropsy examination revealed
      additional nodules in the subcutis and muscles of the trunk and submandibular
      lymph nodes. Genotyping of organisms within these lesions revealed simultaneous
      infection with Mycobacterium avium subsp. avium and Mycobacterium avium subsp.
      hominissuis. The microscopical appearance of the granulomas was identical,
      regardless of the strain of bacterium or anatomical location. 

PMID- 26292771
TI  - Corrigendum to "Development of a loop-mediated isothermal amplification method
      for the rapid detection of the dioxin-degrading bacterium Ochrobactrum antropi in
      soil" [J. Environ. Manag. 161 (2015) 1-8].

PMID- 26292772
TI  - Optimization of wastewater treatment plant operation for greenhouse gas
      mitigation.
AB  - This study deals with the determination of optimal operation of a wastewater
      treatment system for minimizing greenhouse gas emissions, operating costs, and
      pollution loads in the effluent. To do this, an integrated performance index that
      includes three objectives was established to assess system performance. The
      ASMN_G model was used to perform system optimization aimed at determining a set
      of operational parameters that can satisfy three different objectives. The
      complex nonlinear optimization problem was simulated using the Nelder-Mead
      Simplex optimization algorithm. A sensitivity analysis was performed to identify
      influential operational parameters on system performance. The results obtained
      from the optimization simulations for six scenarios demonstrated that there are
      apparent trade-offs among the three conflicting objectives. The best optimized
      system simultaneously reduced greenhouse gas emissions by 31%, reduced operating
      cost by 11%, and improved effluent quality by 2% compared to the base case
      operation. 

PMID- 26292773
TI  - Anaerobic digestion of tomato processing waste: Effect of alkaline pretreatment.
AB  - The objective of the work was to assess the effect of mild alkaline pretreatment
      on the anaerobic biodegradability of tomato processing waste (TPW). Experiments
      were carried out in duplicate BMP bottles using a pretreatment contact time of 4
      and 24 h and a 1% and 5% NaOH dosage. The cumulative methane production during a
      30 d period was recorded and modelled. The alkaline pretreatment did not
      significantly affect methane production in any of the treatments in comparison to
      the control. The average methane production for all runs was 320 NmL/gVS. Based
      on first order kinetic modelling, the alkaline pretreatment was found to slow
      down the rate of methanogenesis, mainly in the two reactors with the highest NaOH
      dosage. The biodegradability of the substrates ranged from 0.75 to 0.82 and from
      0.66 to 0.72 based on two different approaches. 

PMID- 26292774
TI  - Dye adsorption of cotton fabric grafted with PPI dendrimers: Isotherm and kinetic
      studies.
AB  - In this research, the cotton fabrics grafted with two generations of the
      poly(propylene imine) dendrimers were applied to adsorb textile dyes from aqueous
      solutions. Direct Red 80 (anionic dye), Disperse Yellow 42 (nonionic dye) and
      Basic Blue 9 (cationic dye) were selected as model dyes. The effect of various
      experimental parameters such as initial concentration of dyes, charge of dyes
      molecule, salt and pH was investigated on the adsorption process. Furthermore,
      kinetics and equilibrium of the adsorption process on the grafted samples were
      studied. It was found that maximum adsorption of anionic and disperse dyes took
      place at around pH 3, while cationic dye could be adsorbed at around pH 11. The
      Langmuir equation was able to describe the mechanism of dyes adsorption. In
      addition, the second-order equation was found to be fit with the kinetics data.
      Interestingly, it seems that the dye adsorption of the grafted fabrics is
      strongly pH dependent. 

PMID- 26292775
TI  - Application of an electrochemical treatment for EDDS soil washing solution
      regeneration and reuse in a multi-step soil washing process: Case of a Cu
      contaminated soil.
AB  - Soil washing is an extensively used process for remediation of heavy metals
      contaminated soils. However the amount of fresh washing solution to be used
      represents a significant economical drawback of this process. This paper
      investigates the application of an electrochemical process (Fe/Fe electrodes
      couple) for the regeneration of a spent EDDS solution, containing Cu and major
      competitor cations (Ca, Fe, Mg, and Mn). The effect of current density, pH and
      conductivity of the washing solution on the recovery process performances was
      investigated. Current density showed the highest influence on Cu, Mg and Mn
      removal yields. Maximum removal yields reached 99% for Cu, 77% for Mn and 49% for
      Mg. No influence of the investigated parameters on Ca removal was observed, while
      an increase of Fe concentration due to anode dissolution occurred.
      Characterization of sludge produced from the 2 h electrochemical test (5 mA cm(
      2), pH = 8, 8 mS cm(-1)) displayed concentrations of 2.8 g kg(-1) for Ca, 0.4 g
      kg(-1) for Cu, 535.6 g kg(-1) for Fe, 2.6 g kg(-1) for Mg. TCLP tests at pH 2.88
      and 4.93 showed a low leaching percentage (Ca, 10-21%; Cu, 6-12%; Fe, 0.22% Mg,
      27-36%). Multi-washing tests were carried out to assess the decrease of the
      chelating ability of the regenerated washing solution and the Cu extraction
      efficiency. 

PMID- 26292776
TI  - CO2 sequestration using waste concrete and anorthosite tailings by direct mineral
      carbonation in gas-solid-liquid and gas-solid routes.
AB  - Mineral carbonation (MC) represents a promising alternative for sequestering CO2.
      In this work, the CO2 sequestration capacity of the available calcium-bearing
      materials waste concrete and anorthosite tailings is assessed in gas-solid-liquid
      and gas-solid routes using 18.2% flue CO2 gas. The objective is to screen for a
      better potential residue and phase route and as the ultimate purpose to develop a
      cost-effective process. The results indicate the possibility of removing 66% from
      inlet CO2 using waste concrete for the aqueous route. However, the results that
      were obtained with the carbonation of anorthosite were less significant, with 34%
      as the maximal percentage of CO2 removal. The difference in terms of reactivity
      could be explained by the accessibility to calcium. In fact, anorthosite presents
      a framework structure wherein the calcium is trapped, which could slow the
      calcium dissolution into the aqueous phase compared to the concrete sample, where
      calcium can more easily leach. In the other part of the study concerning gas
      solid carbonation, the results of CO2 removal did not exceed 15%, which is not
      economically interesting for scaling up the process. The results obtained with
      waste concrete samples in aqueous phase are interesting. In fact, 34.6% of the
      introduced CO2 is converted into carbonate after 15 min of contact with the gas
      without chemical additives and at a relatively low gas pressure. Research on the
      optimization of the aqueous process using waste concrete should be performed to
      enhance the reaction rate and to develop a cost-effective process. 

PMID- 26292777
TI  - Serum levels of 9alpha,11beta-PGF2 and cysteinyl leukotrienes are useful
      biomarkers of anaphylaxis.

PMID- 26292778
TI  - Effective treatment of house dust mite-induced allergic rhinitis with 2 doses of
      the SQ HDM SLIT-tablet: Results from a randomized, double-blind, placebo
      controlled phase III trial.
AB  - BACKGROUND: The SQ HDM SLIT-tablet (ALK) has been developed for treatment of
      house dust mite (HDM)-induced respiratory allergic disease. OBJECTIVE: This trial
      investigated the efficacy and safety of the SQ HDM SLIT-tablet in adults with
      moderate-to-severe HDM-induced allergic rhinitis (AR). METHODS: The trial was a
      randomized, double-blind, placebo-controlled phase III trial conducted in 12
      European countries including 992 adults with moderate-to-severe HDM-induced AR
      despite treatment with pharmacotherapy. Subjects were randomized 1:1:1 to 1 year
      of daily treatment with placebo, 6 SQ-HDM, or 12 SQ-HDM. The primary end point
      was the total combined rhinitis score (ie, the sum of rhinitis symptom and
      medication scores) during the efficacy assessment period (approximately the last
      8 weeks of the treatment period). Key secondary end points were rhinitis
      symptoms, medication scores, quality of life, and the combined
      rhinoconjunctivitis score. RESULTS: Analysis of the primary end point (observed
      data) demonstrated absolute reductions in total combined rhinitis score of 1.18
      (P = .002) and 1.22 (P = .001) compared with placebo for 6 SQ-HDM and 12 SQ-HDM,
      respectively. The statistically significant treatment effect was evident from 14
      weeks of treatment onward. For all key secondary end points, efficacy was
      confirmed for 12 SQ-HDM, with statistically significant reductions of rhinitis
      symptoms and medication scores, improved quality of life, and a reduced combined
      rhinoconjunctivitis score in the efficacy assessment period compared with
      placebo. The treatment was well tolerated. CONCLUSION: The trial confirmed the
      efficacy and favorable safety profile of both 6 SQ-HDM and 12 SQ-HDM in adults
      with HDM-induced AR. The treatment effect was present from 14 weeks of treatment
      onward.

PMID- 26292780
TI  - Failure mode and effects analysis of witnessing protocols for ensuring
      traceability during IVF.
AB  - Traceability of cells during IVF is a fundamental aspect of treatment, and
      involves witnessing protocols. Failure mode and effects analysis (FMEA) is a
      method of identifying real or potential breakdowns in processes, and allows
      strategies to mitigate risks to be developed. To examine the risks associated
      with witnessing protocols, an FMEA was carried out in a busy IVF centre, before
      and after implementation of an electronic witnessing system (EWS). A
      multidisciplinary team was formed and moderated by human factors specialists.
      Possible causes of failures, and their potential effects, were identified and
      risk priority number (RPN) for each failure calculated. A second FMEA analysis
      was carried out after implementation of an EWS. The IVF team identified seven
      main process phases, 19 associated process steps and 32 possible failure modes.
      The highest RPN was 30, confirming the relatively low risk that mismatches may
      occur in IVF when a manual witnessing system is used. The introduction of the EWS
      allowed a reduction in the moderate-risk failure mode by two-thirds (highest RPN
      = 10). In our experience, FMEA is effective in supporting multidisciplinary IVF
      groups to understand the witnessing process, identifying critical steps and
      planning changes in practice to enable safety to be enhanced. 

PMID- 26292779
TI  - Endemic mycoses in patients with STAT3-mutated hyper-IgE (Job) syndrome.

PMID- 26292781
TI  - [Systemic and localized infection by Candida species in patients with rheumatic
      diseases receiving anti-TNF therapy].
AB  - OBJECTIVE: To evaluate the prevalence of systemic and localized infection by
      Candida species and its possible association with demographic, clinical and
      laboratory manifestations and therapy in patients with rheumatic diseases taking
      TNF blockers. METHODS: Consecutive patients with rheumatic diseases receiving
      anti-TNF agents were included. The following risk factors up to four weeks prior
      to the study were analyzed: use of antibiotics, immunosuppressant drugs,
      hospitalization and invasive procedures. All subjects were evaluated for clinical
      complaints, specific blood cultures were obtained for fungi and blood samples
      were collected for Candida spp. detection by polymerase chain reaction. RESULTS:
      194 patients [67 with rheumatoid arthritis (RA), 47 with ankylosing spondylitis
      (AS), 36 with juvenile idiopathic arthritis (JIA), 28 with psoriatic arthritis
      and 16 with other conditions] were included. The average age of patients was 42+/
      16 years, with 68 (35%) male and mean disease duration of 15+/-10 years. Sixty
      four (33%) patients were receiving adalimumab, 59 (30%) etanercept and 71 (36%)
      infliximab. Eighty-one percent of patients were concomitantly taking
      immunosuppressants drugs. At the time of the study, only one (0.5%) patient had
      localized fungal infection (vaginal candidiasis). None of the patients included
      had systemic candidiasis with positive blood cultures for fungi or PCR positive
      for Candida spp. in peripheral blood sample. CONCLUSIONS: This was the first
      study to assess the prevalence of invasive and localized fungal disease by
      candida in a significant number of patients with rheumatic diseases on anti-TNF
      therapy, and demonstrated low risk of candidiasis, despite the high prevalence of
      immunosuppressive drug use.

PMID- 26292782
TI  - Comparison of full-field digital mammography and digital breast tomosynthesis in
      ultrasonography-detected breast cancers.
AB  - OBJECTIVE: To determine what percentage of cancers, detected by screening
      ultrasonography (US), were detectable by full-field digital mammography (FFDM)
      and digital breast tomosynthesis (DBT). MATERIALS AND METHODS: Eighty-four
      consecutive women in whom mammography was negatively interpreted and
      supplementary screening US initially detected breast cancers at outside hospitals
      underwent both FFDM and DBT. We excluded cases with overt suspicious findings on
      repeat mammography and ineligible cases. In the remaining 41 cases, three
      radiologists who were blinded to tumor location, even though they were aware that
      they had breast cancers independently reviewed both FFDM and DBT. The reference
      standard was the reference FFDM made by two unblinded reviewers who were aware of
      the tumor location and shape on DBT, US, and magnetic resonance imaging (MRI).
      The visibility score based on the correct marking was compared between FFDM and
      DBT. RESULTS: Among the 41 cases, the cancers were visible in 25 (61.0%) on FFDM
      and in 34 (82.9%) on DBT (P = 0.047) by the unblinded review. In the blinded
      analysis, the cancers were significantly more "constantly visible" in the three
      radiologists on DBT than on FFDM [53.7% (22/41) vs. 26.8% (11/41), respectively,
      P = 0.013]. The dominant lesion type was "focal asymmetry" on DBT (39.0%) and
      "asymmetry" on FFDM (31.7%). CONCLUSIONS: Our analysis suggests that 54% of
      cancers that were detected by US and were not evident on 2D mammography were
      detectable by screening using DBT. Additional 29% of cancers were visualized on
      DBT, when the area of concern was known.

PMID- 26292783
TI  - Different levels of precision in studies on the alimentary tract content of
      omnivorous fish affect predictions of their food niche and competitive
      interactions.
AB  - The food niche partitioning of omnivorous fish is commonly estimated on the basis
      of the alimentary tract content (ATC). However, since omnivorous fish utilise
      different ecological formations, data relating to ATC are very noisy, since an
      identified ATC comprises remains that can be determined according to the species
      level, determined only according to general food categories (i.e. higher
      taxonomic levels) as well as amounts of fragmented and digested remains that
      cannot be determined taxonomically. Thus, a variety of scales of precision can be
      applied during work on ATC. Up until now, there has been no evidence as to
      whether and how precision in ATC estimation can affect the results. This study
      aims at assessing how three different options of the same database influence the
      effectiveness and concurrency of indexes commonly used to describe the food niche
      of fish. The options include: (1) only general (higher than species level) food
      categories; (2) categories of different levels of generality; and (3) only
      detailed (species level) food categories. The study shows that the use of
      detailed (species level) food categories only, with the exclusion of general food
      categories, is the best method to recognise food niche partitioning and
      competitive interactions among fish. The food categories estimated in detail were
      cladocerans, and the possibility to use cladocerans as specific markers to find
      similarities in fish diets is discussed. 

PMID- 26292785
TI  - Safety reporting through a comprehensive and pragmatic pharmcovigilance process
      for India and emerging markets: an industry perspective.
AB  - INTRODUCTION: Pharmacovigilance (PV) deals with the drug-related adverse
      reactions ensuring patients' safety. Emerging markets of India, South East Asia
      (SEA), Russia, Latin America (LA), Middle East and North Africa (MENA) have
      developed their own PV programs. However, under/manual reporting accompanied with
      lack of awareness regarding adverse drug reactions (ADRs) are major drawbacks
      that continue to exist due to lack of co-ordination and disparity in the
      regulatory approach. AREAS COVERED: Of the 118 studies identified using various
      databases, 60 were included for the review. The authors discuss the present PV
      scenario of India, SEA, Russia, LA and MENA, and explain a basic process for
      uniform PV data input-output across industry, which includes data collection,
      analysis, processing, causality assessment and data distribution systems. EXPERT
      OPINION: As the number of clinical trials conducted are rising in the emerging
      markets, there is a need to understand and implement a robust PV system, where
      electronically globalized, evidence based, public health oriented and regulatory
      compliant PV system is established. This would also improve transparency in
      system and ensure enhancement in safety data reporting ensuring premature and
      trouble-free detection of ADRs. It might result in implementing various PV
      boosting activities, which could yield robust patient safety data from India and
      emerging markets.

PMID- 26292786
TI  - Sonorensin: A new bacteriocin with potential of an anti-biofilm agent and a food
      biopreservative.
AB  - The emergence of antibiotic resistant bacteria has led to exploration of
      alternative therapeutic agents such as ribosomally synthesized bacterial peptides
      known as bacteriocins. Biofilms, which are microbial communities that cause
      serious chronic infections, form environments that enhance antimicrobial
      resistance. Bacteria in biofilm can be upto thousand times more resistant to
      antibiotics than the same bacteria circulating in a planktonic state. In this
      study, sonorensin, predicted to belong to the heterocycloanthracin subfamily of
      bacteriocins, was found to be effectively killing active and non-multiplying
      cells of both Gram-positive and Gram-negative bacteria. Sonorensin showed marked
      inhibition activity against biofilm of Staphylococcus aureus. Fluorescence and
      electron microscopy suggested that growth inhibition occurred because of
      increased membrane permeability. Low density polyethylene film coated with
      sonorensin was found to effectively control the growth of food spoilage bacteria
      like Listeria monocytogenes and S. aureus. The biopreservative effect of
      sonorensin coated film showing growth inhibition of spoilage bacteria in chicken
      meat and tomato samples demonstrated the potential of sonorensin as an
      alternative to current antibiotics/ preservatives. 

PMID- 26292787
TI  - Dermatitis in the Fringe-Toed Lizard, Acanthodactylus nilsoni Rastegar-Pouyani,
      1998 (Sauria: Lacertidae) Associated with Fusarium proliferatum.
AB  - From July to October 2013, nine out of 40 Acanthodactylus nilsoni collected from
      Western Iran, showed clinical signs of dermatitis in the dorsal and ventral
      surface of neck and fingers. Therefore, the aim of this survey was to identify
      the fungal flora colonizing the skin of A. nilsoni using morphological and
      molecular studies. Nine isolates of Fusarium were obtained from infected lizard
      samples and identified as Fusarium proliferatum through study of morphological
      characters. In the present study, selected F. proliferatum isolates (USMGFSC 230
      112, USMGFSC 186-113, and USMGFSC 33-114) were examined and phylogenetically
      analysed on the basis of partial sequences of the tef1 and tub2 genes. Sequence
      analysis supported the morphological data, and all isolates were placed within F.
      proliferatum species. This is the first report on morphological and molecular
      identification of F. proliferatum isolated from lizards' dermatitis in Iran.

PMID- 26292788
TI  - Recent advances in orthostatic hypotension presenting orthostatic dizziness or
      vertigo.
AB  - Orthostatic hypotension (OH), a proxy for sympathetic adrenergic failure, is the
      most incapacitating sign of autonomic failure. Orthostatic dizziness (OD) is
      known to be the most common symptom of OH. However, recent studies have
      demonstrated that 30-39 % of patients with OH experienced rotatory vertigo during
      upright posture (i.e., orthostatic vertigo, OV), which challenges the dogma that
      OH induces dizziness and not vertigo. A recent population-based study on
      spontaneously occurring OD across a wide age range showed that the one-year and
      lifetime prevalence of OD was 10.9 and 12.5 %, respectively. Approximately 83 %
      of patients with OD had at least one abnormal autonomic function test result. So
      far, 11 subtypes of OD have been proposed according to the pattern of autonomic
      dysfunction, and generalized autonomic failure of sympathetic adrenergic and
      parasympathetic cardiovagal functions was the most common type. Four different
      patterns of OH, such as classic, delayed, early, and transient type have been
      found in patients with OD. The head-up tilt test and Valsalva maneuver should be
      performed for a comprehensive evaluation of sympathetic adrenergic failure in
      patients with OD/OV. This review summarizes current advances in OH presenting
      OD/OV, with a particular focus on the autonomic dysfunction associated with OD. 

PMID- 26292789
TI  - Source localization of intermittent rhythmic delta activity in a patient with
      acute confusional migraine: cross-spectral analysis using standardized low
      resolution brain electromagnetic tomography (sLORETA).
AB  - Acute confusional migraine (ACM) shows typical electroencephalography (EEG)
      patterns of diffuse delta slowing and frontal intermittent rhythmic delta
      activity (FIRDA). The pathophysiology of ACM is still unclear but these patterns
      suggest neuronal dysfunction in specific brain areas. We performed source
      localization analysis of IRDA (in the frequency band of 1-3.5 Hz) to better
      understand the ACM mechanism. Typical IRDA EEG patterns were recorded in a
      patient with ACM during the acute stage. A second EEG was obtained after recovery
      from ACM. To identify source localization of IRDA, statistical non-parametric
      mapping using standardized low-resolution brain electromagnetic tomography was
      performed for the delta frequency band comparisons between ACM attack and non
      attack periods. A difference in the current density maximum was found in the
      dorsal anterior cingulated cortex (ACC). The significant differences were widely
      distributed over the frontal, parietal, temporal and limbic lobe, paracentral
      lobule and insula and were predominant in the left hemisphere. Dorsal ACC
      dysfunction was demonstrated for the first time in a patient with ACM in this
      source localization analysis of IRDA. The ACC plays an important role in the
      frontal attentional control system and acute confusion. This dysfunction of the
      dorsal ACC might represent an important ACM pathophysiology.

PMID- 26292790
TI  - Rituximab as a first-line treatment in pediatric neuromyelitis optica spectrum
      disorder.

PMID- 26292791
TI  - Safety and efficacy of primary central nervous system lymphoma treatment in
      elderly population.
AB  - Elderly patients represent an important subgroup in primary central nervous
      system lymphoma (PCNSL) that accounts for approximately half the cases.
      Furthermore age represents one of the heaviest prognostic factors and in some
      cases it has more effect on survival than therapies. We performed a retrospective
      analysis to assess the toxicity and the efficacy of high-dose methotrexate
      (HDMTX) chemotherapy in a PCNSL population older than 70 years. Seventeen
      consecutive immunocompetent patients older than 70 years, with histologically
      confirmed PCNSL, without systemic involvement, treated with HDMTX at our
      institution between May 2005 and April 2013, were retrospectively evaluated. Main
      outcome measures were acute toxicity and tumour response. No evidence of
      haematological toxicity was recorded in 47 % of patients and no deaths related to
      toxicity grade were reported. Patients achieved a partial response after 3 cycles
      of chemotherapy in 53 % of cases. The median overall survival (m-OS) from
      diagnosis was 20.9 months (range 5.2-34 months), with OS-12 of 58.8 % and an OS
      24 of 45.4 %. Since there is no standard of care in the treatment of PCNSL in
      elderly population, it should be taken into account that elderly patients not
      always can be considered "fragile" and the general tendency to less treat to
      avoid severe toxicity should not be the rule.

PMID- 26292792
TI  - Effect of cassava bioethanol by-product and crude palm oil in Brahman x Thai
      native yearling heifer cattle diets: II. Carcass characteristics and meat
      quality.
AB  - This experiment was conducted to determine the effects of cassava bioethanol by
      product (CEP) and crude palm oil (CPO) on the carcass characteristics and meat
      quality of yearling heifer cattle. Eighteen crossbred Brahman * Thai heifers were
      randomly allotted to 2 * 3 factorial arrangement consisting of two levels of CEP
      (15 or 30 %, LCEP or HCEP) and 3 levels of CPO (0, 2, and 4 %). The results
      obtained showed that lean meat was greater (P < 0.05) in HCEP-fed cattle, but
      bone percentage and lean/bone ratio were less (P < 0.05) than LCEP-fed cattle.
      Carcass fat (P < 0.05) and fat content (P < 0.01) were significantly increased
      with levels of dietary CPO. Diets with 4 % CPO supplementation had better effects
      on redness (a*, P < 0.01) and chroma (C*, P < 0.001) values. In conclusion, up to
      30 % CEP can be used to improve lean carcass and 4 % CPO can improve the redness
      of the meat. 

PMID- 26292793
TI  - Capturing patients' experiences to change Parkinson's disease care delivery: a
      multicenter study.
AB  - Capturing patients' perspectives has become an essential part of a quality of
      care assessment. The patient centeredness questionnaire for PD (PCQ-PD) has been
      validated in The Netherlands as an instrument to measure patients' experiences.
      This study aims to assess the level of patient centeredness in North American
      Parkinson centers and to demonstrate the PCQ-PD's potential as a quality
      improvement instrument. 20 Parkinson Centers of Excellence participated in a
      multicenter study. Each center asked 50 consecutive patients to complete the
      questionnaire. Data analyses included calculating case mix-adjusted scores for
      overall patient centeredness (scoring range 0-3), six subscales (0-3), and
      quality improvement (0-9). Each center received a feedback report on their
      performance. The PCQ-PD was completed by 972 PD patients (median 50 per center,
      range 37-58). Significant differences between centers were found for all
      subscales, except for emotional support (p < 0.05). The information subscale
      (mean 1.62 SD 0.62) and collaboration subscale (mean 2.03 SD 0.58) received the
      lowest experience ratings. 14 centers (88 %) who returned the evaluation survey
      claimed that patient experience scores could help to improve the quality of care.
      Nine centers (56 %) utilized the feedback to change specific elements of their
      care delivery process. PD patients are under-informed about critical care issues
      and experience a lack of collaboration between healthcare professionals. Feedback
      on patients' experiences facilitated Parkinson centers to improve their delivery
      of care. These findings create a basis for collecting patients' experiences in a
      repetitive fashion, intertwined with existing quality of care registries.

PMID- 26292794
TI  - Retinopathy during interferon-beta treatment for multiple sclerosis: case report
      and review of the literature.
AB  - The onset of new visual symptoms in patients with multiple sclerosis is often
      associated with a neuro-ophthalmologic manifestation of the disease. However,
      other possible differential diagnoses need to be ruled out, including drug
      induced retinal side effects. Although uncommon, retinal side effects of
      interferon-beta formulations may occur, and need to be promptly recognized and
      treated by neurologists. In this manuscript, we report the case of a 37-year-old
      woman affected by multiple sclerosis diagnosed with interferon beta-associated
      retinopathy and we review the literature with regard to the epidemiology,
      clinical presentation, management and follow-up of interferon beta-associated
      retinopathy. Interferon-beta induced retinopathy seems to be an uncommon and a
      dose-related side effect in multiple sclerosis patients. Retinopathy tends to
      completely resolve after treatment discontinuation. Neurologists must be aware
      that immune-modulatory drugs, in particular interferon beta, have been reported
      to cause retinal side effects. In multiple sclerosis patients complaining of new
      visual symptoms during interferon-beta treatment, it is thus advisable to perform
      an ophthalmological assessment to rule out and properly manage retinopathy. 

PMID- 26292795
TI  - The Perception of Benefit of Vocalization on Sport Performance When Producing
      Maximum Effort.
AB  - OBJECTIVES/HYPOTHESIS: The purpose of this study was to describe athlete belief
      of performance benefit when using voice during force production tasks and to
      determine if vocalization during effortful tasks was correlated to perception of
      voice impairment. The hypotheses were as follows: (1) there is a belief among
      athletes that voicing during high-effort tasks improves performance and (2) the
      use of the voice during high-effort tasks is correlated with the perception of
      voice impairment. STUDY DESIGN: An anonymous, online survey was used to query
      presence and timing of voicing during force production. The Voice Handicap Index
      10 and a visual analog scale for perceived phonatory effort were included in the
      survey. METHODS: The data obtained from the survey were evaluated using
      descriptive statistics and analysis of variance. Correlation coefficients were
      calculated to determine if there was a relationship between voice production and
      the perception of voice disorder. RESULTS: Three hundred seventy-eight
      participants' survey responses were used in the data analyses. The results
      indicated that 56% of the participating athletes indicated belief that the
      production of voice during maximum effort provided a performance advantage. There
      was no correlation between individuals who used voice during force production and
      the perception of voice impairment. CONCLUSIONS: Findings indicated that most
      athletes believe that producing voice during maximum effort improves performance
      without a perception of voice impairment. Further research should be completed to
      objectively measure force production in both grunt and nongrunt trials
      concurrently with measures of vocal function.

PMID- 26292796
TI  - Effectiveness of Chewing Technique on the Phonation of Female Speech-Language
      Pathology Students: A Pilot Study.
AB  - OBJECTIVES: The purpose of this study was to determine how use of the vocal
      facilitating technique, chewing, affected the phonation of speech-language
      pathology (SLP) students. STUDY DESIGN: A pretest-posttest randomized control
      group design was used. METHODS: Twenty-seven healthy female SLP students were
      randomly assigned into either an experimental group or a control group. The
      experimental group practiced chewing exercises across 18 weeks, whereas the
      control group received no vocal facilitating techniques. Both groups completed
      pre- and post- objective voice assessment measures (aerodynamic measurement,
      acoustic analysis, voice range profile, and Dysphonia Severity Index).
      Differences between pre- and post-data were compared between the experimental and
      control group using an independent sample t test. RESULTS: Compared to the
      control group, chewing resulted in a significant decrease in jitter and noise-to
      harmonic ratio (NHR), a significant increase in fundamental frequency (fo), a
      significant expansion of the voice range profile, and a significant increase in
      Dysphonia Severity Index (DSI). Shimmer and maximum phonation time (MPT) were not
      significantly different between groups. CONCLUSIONS: The results of this pilot
      study suggest that the vocal facilitating technique, chewing, may improve
      objective vocal measures in healthy female SLP students.

PMID- 26292797
TI  - Quantification of Porcine Vocal Fold Geometry.
AB  - OBJECTIVE: The aim of this study was to quantify porcine vocal fold medial
      surface geometry and three-dimensional geometric distortion induced by freezing
      the larynx, especially in the region of the vocal folds. STUDY DESIGN: The medial
      surface geometries of five excised porcine larynges were quantified and reported.
      METHODS: Five porcine larynges were imaged in a micro-CT scanner, frozen, and
      rescanned. Segmentations and three-dimensional reconstructions were used to
      quantify and characterize geometric features. Comparisons were made with geometry
      data previously obtained using canine and human vocal folds as well as geometries
      of selected synthetic vocal fold models. RESULTS: Freezing induced an overall
      expansion of approximately 5% in the transverse plane and comparable levels of
      nonuniform distortion in sagittal and coronal planes. The medial surface of the
      porcine vocal folds was found to compare reasonably well with other geometries,
      although the compared geometries exhibited a notable discrepancy with one set of
      published human female vocal fold geometry. CONCLUSIONS: Porcine vocal folds are
      qualitatively geometrically similar to data available for canine and human vocal
      folds, as well as commonly used models. Freezing of tissue in the larynx causes
      distortion of around 5%. The data can provide direction in estimating uncertainty
      due to bulk distortion of tissue caused by freezing, as well as quantitative
      geometric data that can be directly used in developing vocal fold models.

PMID- 26292798
TI  - Linguistic Adaptation, Reliability, Validation, and Responsivity of the Chinese
      Version of Reflux Symptom Index.
AB  - OBJECTIVES: Currently, there is no cost-effective tool available to diagnose
      laryngopharyngeal reflux (LPR) in the developing country of China. The aim of
      this study was to achieve a linguistic adaptation of the Chinese version of the
      Reflux Symptom Index (RSI-CH). STUDY DESIGN: A nonrandomized, controlled,
      prospective trial. METHODS: A total of 107 patients at the outpatient clinic of
      Peking University People's Hospital were enrolled. They were asked to fill out
      the RSI-CH and underwent fiber-optic laryngoscopy to complete the Reflux Finding
      Score (RFS). Patients underwent pH monitoring if the RSI-CH was greater than 13
      or if the RFS was not less than 7. Patients were treated with Omeprazole 20 mg
      twice a day for 3 months if the pH monitoring was positive. The reliability
      (Cronbach alpha coefficient and Spearman correlation analysis), validity
      (sensitivity, specificity, and positive and negative predictive values), and
      responsivity of RSI-CH were determined. RESULTS: RSI-CH had a good reliability
      (Cronbach alpha coefficient was greater than .7, whereas the test-retest validity
      for the total score and for each item were 0.750-0.971. The scale had a good
      criterion validity. The consistency (66.7%), sensitivity (61.76%), and
      specificity (75%), and the positive and negative predictive values (80.8% and
      53.6%) were considered good. The RSI-CH scores changed from 15 to 7 after
      treatment, and the average score of the controlled group was 6.5. CONCLUSIONS:
      The RSI-CH developed and validated by this study can be used as an effective
      diagnostic tool in identifying differentiating LPR diseases in patients whose
      native language is Chinese.

PMID- 26292799
TI  - Treatment of Acute Vocal Fold Injury With Platelet-Rich Plasma.
AB  - OBJECTIVES: Platelet-rich plasma (PRP) is a reliable and has low side-effect
      profile and has beneficial effects on wound healing. Its investigatory effects on
      wound-healing process were shown on various tissues. The aim of the present study
      was to evaluate effectiveness of PRP application on scar tissue of acute vocal
      fold injury. MATERIALS AND METHODS: Twenty-four Wistar rats were used in the
      study. The entire layer of the lamina propria down to the thyroarytenoid muscle
      of 10 subjects was unilaterally injured by with a microscissor. Gelfoam-absorbed
      PRP was applied on the injured area for 10 minutes. Control group consisted of
      rats unilaterally injured using a microscissor, and gelfoam with normal saline
      was applied on the injured area. Following sacrifice, the larynxes were carefully
      dissected and removed for histopathologic examination. After excised larynx
      experiments, serial sections were prepared from vocal fold. Hematoxylin eosin and
      immunohistochemical staining were done for epithelial growth factor receptor
      (EGFR), fibroblast growth factor receptor (FGFR1), and vascular endothelial
      growth factor (VEGF) staining for histopathologic examinations. RESULTS: There
      was not a significant difference between the two groups for lymphocyte. Although
      collagen and VEGF were higher in the study group, there was not a significant
      difference between the groups (P > 0.05). There was a significant difference
      between control and study groups for EGFR and FGFR1(P < 0.05). CONCLUSIONS: PRP
      has beneficial effects on wound healing. PRP accelerates epithelization of
      injured rat vocal folds by inducing EGFR secretion. PRP is an autogenous,
      reliable, low side-effect profile, easily harvested material. PRP may be useful
      to prevent scar formation.

PMID- 26292800
TI  - Reduced blastocyst formation in reduced culture volume.
AB  - PURPOSE: The aim of this prospective sibling oocyte study was to evaluate whether
      reduced culture volume improves blastocyst formation. METHODS: Twenty-three
      patients with extended embryo culture until day 5 were selected for the study.
      After injection, 345 sibling oocytes were individually cultured in either 25 or 7
      MUl droplets of Origio cleavage medium under oil. On day 3 of development,
      embryos were transferred to droplets with the corresponding volume of Origio
      blastocyst culture medium. Fertilization and embryo quality on day 3 and day 5/6
      were evaluated. RESULTS: No statistically significant difference (p = 0.326) in
      fertilization rate was observed (81.3 versus 83.0 %). There was no significant
      difference in terms of the number of excellent and good-quality embryos obtained
      on day 3 between both groups (p = 0.655). Embryo culture in 25 MUl droplets led
      to more embryos with a higher cell number when compared to 7 MUl culture (p =
      0.024). On day 3, 132 and 131 embryos were considered for further culture until
      day 5/6. Blastulation rates were significantly higher in the 25 MUl group (75.0
      versus 61.6 %; p = 0.017) and significantly more day 5 embryos with excellent and
      good quality were found in this group (54.5 versus 40.5 %; p = 0.026). Finally,
      the utilization rates expressed per mature oocyte (41.4 versus 29.8 %; p =
      0.043), per fertilized oocyte (50.7 versus 36.6 %; p = 0.023), and per day 3
      embryo undergoing extended culture to day 5/6 (54.5 versus 39.7 %; p = 0.019)
      were all significantly higher in the 25 MUl group. CONCLUSION: Reduced culture
      volume (7 MUl) negatively impacts early development by reducing the cell number
      on day 3 and both blastocyst formation and quality.

PMID- 26292801
TI  - Role of ethanol-derived acetaldehyde in operant oral self-administration of
      ethanol in rats.
AB  - RATIONALE: The role of ethanol-derived acetaldehyde has not been examined yet on
      performance in a model of operant oral self-administration. However, previous
      studies reported that an acetaldehyde-sequestering agent, D-penicillamine (DP)
      and an inhibitor of catalase-mediated acetaldehyde production, 3-amino-1,2,4
      triazole (3-AT) reduce voluntary ethanol consumption. OBJECTIVES: The aim of our
      investigation was to evaluate the effects of DP and 3-AT on acquisition and
      maintenance of oral operant ethanol self-administration. METHODS: Using operant
      chambers, rats learned to nose poke in order to receive ethanol solution (5-10 %
      v/v) under an FR1 schedule of reinforcement in which discrete light and tone cues
      were presented during ethanol delivery. RESULTS: DP and 3-AT impair the
      acquisition of ethanol self-administration, whereas its maintenance is not
      affected neither by drug given alone for both 10 or 5 % ethanol nor by drugs
      association for 5 % ethanol. Moreover, when the concentration of ethanol was
      diminished from 10 to 5 %, rats increased the rate of self-administration
      behaviour. CONCLUSIONS: These findings suggest that brain acetaldehyde plays a
      critical role during acquisition of operant self-administration in ethanol-naive
      rats. In contrast, during the maintenance phase, acetaldehyde could contribute to
      ethanol self-administration by a combined mechanism: On one hand, its lack (by DP
      or 3-AT) might result in further ethanol-seeking and taking and, on the other,
      inhibition of ethanol metabolism (by 3-AT) might release an action of the un
      metabolised fraction of ethanol that does not overall result in compromising
      maintenance of ethanol self-administration.

PMID- 26292802
TI  - Glutamatergic system abnormalities in posttraumatic stress disorder.
AB  - RATIONALE: Accumulating evidence suggests involvement of the glutamatergic system
      in the biological mechanisms of posttraumatic stress disorder (PTSD), but few
      studies have demonstrated an association between glutamatergic system
      abnormalities and PTSD diagnosis or severity. OBJECTIVE: We aimed to examine
      whether abnormalities in serum glutamate and in the glutamine/glutamate ratio
      were associated with PTSD diagnosis and severity in severely injured patients at
      risk for PTSD and major depressive disorder (MDD). METHODS: This is a nested case
      control study in TPOP (Tachikawa project for prevention of posttraumatic stress
      disorder with polyunsaturated fatty acid) trial. Diagnosis and severity of PTSD
      were assessed 3 months after the accidents using the Clinician-Administered PTSD
      Scale. The associations of glutamate levels and the glutamine/glutamate ratio
      with diagnosis and severity of PTSD and MDD were investigated by univariate and
      multiple linear regression analyses. RESULTS: Ninety-seven of 110 participants
      (88 %) completed assessments at 3 months. Serum glutamate levels were
      significantly higher for participants with full or partial PTSD than for
      participants without PTSD (p = 0.049) and for participants with MDD than for
      participants without MDD (p = 0.048). Multiple linear regression analyses showed
      serum glutamate levels were significantly positively associated with PTSD
      severity (p = 0.02) and MDD severity (p = 0.03). The glutamine/glutamate ratio
      was also significantly inversely associated with PTSD severity (p = 0.03), but
      not with MDD severity (p = 0.07). CONCLUSIONS: These findings suggest that the
      glutamatergic system may play a major role in the pathogenesis of PTSD and the
      need for new treatments targeting the glutamatergic system to be developed for
      PTSD.

PMID- 26292804
TI  - Generalisation within specialization: inter-individual diet variation in the only
      specialized salamander in the world.
AB  - Specialization is typically inferred at population and species level but in the
      last decade many authors highlighted this trait at the individual level, finding
      that generalist populations can be composed by both generalist and specialist
      individual. Despite hundreds of reported cases of individual specialization there
      is a complete lack of information on inter-individual diet variation in
      specialist species. We studied the diet of the Italian endemic Spectacled
      Salamander (Salamandrina perspicillata), in a temperate forest ecosystem, to
      disclose the realised trophic niche, prey selection strategy in function of
      phenotypic variation and inter-individual diet variation. Our results showed that
      Salamandrina is highly specialized on Collembola and the more specialized
      individuals are the better performing ones. Analyses of inter-individual diet
      variation showed that a subset of animals exhibited a broader trophic niche,
      adopting different foraging strategies. Our findings reflects the optimal
      foraging theory both at population and individual level, since animals in better
      physiological conditions are able to exploit the most profitable prey, suggesting
      that the two coexisting strategies are not equivalent. At last this species,
      feeding on decomposers of litter detritus, could play a key role determining
      litter retention rate, nutrient cycle and carbon sequestration. 

PMID- 26292803
TI  - Immunological Consequences of JAK Inhibition: Friend or Foe?
AB  - Over the last decade, unparalleled advances have been made within the field of
      'Philadelphia chromosome'-negative myeloproliferative neoplasms (MPN) regarding
      both disease pathogenesis and therapeutic targeting. The discovery of deregulated
      JAK-STAT signalling in MPN led to the rapid development of JAK inhibitor agents,
      targeting both mutated and wild-type JAK, which have significantly altered the
      therapeutic paradigm for patients with MPN. Although the largest population
      treated with these agents incorporates those with myelofibrosis, increasing data
      supports potential usage in other MPNs such as essential thromocythaemia and
      polycythaemia vera. Many MPNs are associated with a hyperinflammatory state and
      deregulation of immune homeostasis. Over the last few years, research has focused
      on attempting to decipher the complex and context-dependent changes that
      contribute to this immune deregulation. Moreover, very recent studies have
      demonstrated significant JAK inhibitor-mediated effects within the T cell,
      natural killer cell and dendritic cell compartments following exposure to JAK
      inhibitors. In parallel, case reports of infections occurring following exposure
      to ruxolitinib, many of which are atypical, have focused research efforts on
      delineating JAK inhibitor-associated immunological consequences. Within this
      review article, we will describe what is currently known about MPN-associated
      immune deregulation and JAK inhibitor-mediated immunomodulation. 

PMID- 26292805
TI  - Effects of limiting fluid intake on clinical and laboratory outcomes in patients
      with heart failure. Results of a meta-analysis of randomized controlled trials.
AB  - BACKGROUND: The guidelines of the Scientific Societies of Cardiology recommend
      limiting fluid intake as a nonpharmacological measure for the management of
      chronic heart failure (HF). However, many patients with HF may suffer from severe
      thirst. A meta-analysis was performed to evaluate the effect of limiting fluid
      consumption based on various clinical and laboratory outcomes in patients with
      chronic HF. METHODS: Only randomized controlled trials comparing liberal and
      restricted fluid oral intake in patients with HF were included. Primary outcomes
      were HF hospitalizations and all-cause mortality. Secondary outcomes were the
      sensation of thirst, the duration of therapy with intravenous diuretics, and the
      serum levels of creatinine, sodium, and B-type natriuretic peptide (BNP).
      RESULTS: Six studies met the inclusion criteria. Significant heterogeneity was
      detected for the majority of outcomes. In 5 studies, patients with restricted
      fluid intake compared to patients with free consumption of beverages had similar
      rehospitalization and mortality rates. There were no differences regarding
      patients' sense of thirst (4 studies), duration of intravenous diuretic treatment
      (2 studies), serum creatinine levels (5 studies), and serum sodium levels (5
      studies). Serum BNP levels were significantly higher in the group with free fluid
      intake (4 studies). CONCLUSION: In patients with HF, liberal fluid consumption
      does not seem to exert an unfavorable impact on HF rehospitalizations or all
      cause mortality. Further randomized controlled trials are warranted to
      definitively confirm the present findings.

PMID- 26292806
TI  - DNA methylation loci associated with atopy and high serum IgE: a genome-wide
      application of recursive Random Forest feature selection.
AB  - BACKGROUND: The prevalence of allergic diseases are increasing worldwide,
      emphasizing the need to elucidate their pathogeneses. The aims of this study were
      to use a two-stage design to identify DNA methylation levels at cytosine
      phosphate-guanine (CpG) sites across the genome associated with atopy and high
      serum immunoglobulin E (IgE), then to replicate our findings in an independent
      cohort. METHODS: Atopy was assessed via skin prick tests and high serum IgE.
      Methylation levels were measured from whole blood using the Illumina Infinium
      HumanMethylation450 BeadChip from 18-year-old women (n = 245) and men (n = 122)
      in the Isle of Wight birth cohort. After data cleaning and processing, and
      removing probes with possible single nucleotide polymorphisms, DNA methylation
      levels from 254,460 CpG sites from the 245 women were subjected to recursive
      Random Forest feature selection for stage 1. The sites selected from stage 1 were
      tested in stage 2 for associations with atopy and high IgE levels (>200 kU/L) via
      logistic regression adjusted for predicted cell-type proportions and sex. Sites
      significantly associated with atopy in stage 2 underwent replication tests in the
      independent Swedish birth cohort BAMSE (n = 464). RESULTS: In stage 1, 62 sites
      were selected, of which 22 were associated with atopy in stage 2 (P-value range
      6.5E-9 to 1.4E-5) and 12 associated with high IgE levels (P-value range 1.1E-5 to
      7.1E-4) at the Bonferroni adjusted alpha (0.05/62 = 0.0008). Of the 19 available
      sites, 13 were replicated. CONCLUSIONS: We identified 13 novel epigenetic loci
      associated with atopy and high IgE that could serve as candidate loci for future
      studies; four were within genes with known roles in the immune response
      (cg04983687 in the body of ZFPM1, cg18219873 in the 5'UTR of PRG2, cg27469152 in
      the 3'UTR of EPX, and cg09332506 in the body of COPA).

PMID- 26292807
TI  - Neutrophil count is associated with survival in localized prostate cancer.
AB  - BACKGROUND: Increasing evidence suggests a close relationship between systemic
      inflammation and cancer development and progression. The neutrophil to lymphocyte
      ratio (NLR) has been shown to be an independent prognostic indicator in various
      advanced and localized cancers. We investigated the influence of markers of
      systemic inflammation such as leucocyte counts and metabolic co-morbidities on
      overall survival (OS) after radiotherapy for localized prostate cancer. METHODS:
      We conducted a retrospective study of patients with localized prostate cancer
      treated with definitive external beam radiotherapy or brachytherapy. Univariate
      and multivariate cox proportional hazards models were used to investigate the
      influence of the following factors on OS: age, neutrophil and lymphocyte counts,
      neutrophil-to-lymphocyte ratio (NLR), Cancer of the Prostate Risk Assessment
      (CAPRA) score as well as comorbidities associated with inflammation such as
      cardiac history, diabetes and use of a statin. A stepwise selection of variable
      based on the Akaike information criterion (AIC) was used for multivariate
      analysis. RESULTS: In total, 1772 pts were included; blood count data was
      available for 950 pts. Median age was 68 years (44-87). Actuarial 5 years OS and
      biochemical recurrence-free survival (BRFS) for the 1772 patients were 93% and
      95%, respectively, with a median follow-up of 44 months (1-156). On univariate
      analysis, neutrophil count (p = 0.04), cardiac history (p = 0.008), age (p =
      0.001) and CAPRA (p = 0.0002) were associated with OS. Lymphocytes, NLR and
      comorbidities other than cardiac history were not associated with mortality. On
      multivariate analysis, neutrophil count (HR = 1.18, 95 % CI: 1.017-1.37, p =
      0.028), age (HR = 1.06, 95 % CI: 1.01-1.1, p = 0.008) and CAPRA (HR = 1.16, 95 %
      CI: 1.03-1.31, p = 0.015) were independent predictors of OS. CONCLUSION:
      Neutrophil count, as a possible marker of systemic inflammation, appear to be an
      independent prognostic factor for overall mortality in localized prostate cancer.
      A validation cohort is needed to corroborate these results.

PMID- 26292809
TI  - Mandibular condylar morphology for bruxers with different grinding patterns.
AB  - OBJECTIVES: The purpose of this study was to investigate the mandibular condylar
      morphology for bruxers with different grinding patterns. METHOD: Condylar
      sectional morphology and condylar position of 30 subjects were determined by two
      viewers using cone beam computed tomography (CBCT) image data sets. The grinding
      patterns during sleep bruxism (SB) were determined objectively using a Brux
      checker device.Chi-square tests were used for statistical analysis for the
      condylar morphology type between different tooth grinding patterns. Spearman's
      rank correlation coefficient was used for correlation analysis between condylar
      position and the canine guidance area during SB. RESULTS: Theincidence of
      condylarmorphologicaldivergence from idealwas35%.There isa significant difference
      in distribution of condylar morphology type between the group grinding (GG) and
      GG combined with mediotrusive side grinding (MG) (p < 0.05). There was no
      significant correlation between condylar position and canine guidance area during
      bruxism. DISCUSSION: MG during SB is associated with condylar morphology that is
      considered not to be ideal.

PMID- 26292808
TI  - Ultrastructural and functional fate of recycled vesicles in hippocampal synapses.
AB  - Efficient recycling of synaptic vesicles is thought to be critical for sustained
      information transfer at central terminals. However, the specific contribution
      that retrieved vesicles make to future transmission events remains unclear. Here
      we exploit fluorescence and time-stamped electron microscopy to track the
      functional and positional fate of vesicles endocytosed after readily releasable
      pool (RRP) stimulation in rat hippocampal synapses. We show that most vesicles
      are recovered near the active zone but subsequently take up random positions in
      the cluster, without preferential bias for future use. These vesicles non
      selectively queue, advancing towards the release site with further stimulation in
      an actin-dependent manner. Nonetheless, the small subset of vesicles retrieved
      recently in the stimulus train persist nearer the active zone and exhibit more
      privileged use in the next RRP. Our findings reveal heterogeneity in vesicle fate
      based on nanoscale position and timing rules, providing new insights into the
      origins of future pool constitution. 

PMID- 26292832
TI  - Towards an understanding of medical student resilience in longitudinal integrated
      clerkships.
AB  - BACKGROUND: Resilience is required to succeed academically, overcome challenges
      during clinical training and cope positively with stress in future professional
      life. With medical students at high risk of mental illness, socially accountable
      medical schools are seeking to foster student resilience. This exploratory study
      proposes a conceptual framework for student resilience in longitudinal integrated
      clerkships (LICs). METHODS: This qualitative study sought to understand student
      resilience during the first year of clinical training in a rural LIC where there
      were consistent anecdotal reports of high student resilience. In-depth interviews
      were conducted with a purposive sample of 19 medical students, professional staff
      and clinician teachers. An interpretive approach was used to analyse the data
      with emerging concepts compared to define evolving theoretical constructs, and
      develop a conceptual framework. RESULTS: LIC students experienced adversity
      during the first clinical year of the medical course due to challenges
      encountered in the learning environment. This distress was moderated by: a
      secure, supportive learning environment; their profound learning journey; and
      utilisation of organisational structures to stay on course. CONCLUSION: This
      triad of inter-related themes forms a conceptual model that challenges simplistic
      notions that medical courses should focus solely on providing tangible and
      emotional supports for students. How LIC programs may contribute to student
      wellbeing is discussed through the lenses of agentic, reflective and
      transformative learning.

PMID- 26292834
TI  - Loss of the sulfate transporter Slc13a4 in placenta causes severe fetal
      abnormalities and death in mice.

PMID- 26292833
TI  - Direct reprogramming of mouse fibroblasts into cardiomyocytes with chemical
      cocktails.
AB  - The direct conversion, or transdifferentiation, of non-cardiac cells into
      cardiomyocytes by forced expression of transcription factors and microRNAs
      provides promising approaches for cardiac regeneration. However, genetic
      manipulations raise safety concerns and are thus not desirable in most clinical
      applications. The discovery of full chemically induced pluripotent stem cells
      suggest the possibility of replacing transcription factors with chemical
      cocktails. Here, we report the generation of automatically beating cardiomyocyte
      like cells from mouse fibroblasts using only chemical cocktails. These chemical
      induced cardiomyocyte-like cells (CiCMs) express cardiomyocyte-specific markers,
      exhibit sarcomeric organization, and possess typical cardiac calcium flux and
      electrophysiological features. Genetic lineage tracing confirms the fibroblast
      origin of these CiCMs. Further studies show the generation of CiCMs passes
      through a cardiac progenitor stage instead of a pluripotent stage. Bypassing the
      use of viral-derived factors, this proof of concept study lays a foundation for
      in vivo cardiac transdifferentiation with pharmacological agents and possibly
      safer treatment of heart failure. 

PMID- 26292835
TI  - Efficiency of Collisional O2 + N2 Vibrational Energy Exchange.
AB  - By following the scheme of the Grid Empowered Molecular Simulator (GEMS), a new
      O2 + N2 intermolecular potential, built on ab initio calculations and
      experimental (scattering and second virial coefficient) data, has been coupled
      with an appropriate intramolecular one. On the resulting potential energy surface
      detailed rate coefficients for collision induced vibrational energy exchanges
      have been computed using a semiclassical method. A cross comparison of the
      computed rate coefficients with the outcomes of previous semiclassical
      calculations and kinetic experiments has provided a foundation for characterizing
      the main features of the vibrational energy transfer processes of the title
      system as well as a critical reading of the trajectory outcomes and kinetic data.
      On the implemented procedures massive trajectory runs for the proper interval of
      initial conditions have singled out structures of the vibrational distributions
      useful to formulate scaling relationships for complex molecular simulations. 

PMID- 26292836
TI  - Impact of the Crystallite Orientation Distribution on Exciton Transport in Donor
      Acceptor Conjugated Polymers.
AB  - Conjugated polymers are widely used materials in organic photovoltaic devices.
      Owing to their extended electronic wave functions, they often form
      semicrystalline thin films. In this work, we aim to understand whether
      distribution of crystallographic orientations affects exciton diffusion using a
      low-band-gap polymer backbone motif that is representative of the donor/acceptor
      copolymer class. Using the fact that the polymer side chain can tune the dominant
      crystallographic orientation in the thin film, we have measured the quenching of
      polymer photoluminescence, and thus the extent of exciton dissociation, as a
      function of crystal orientation with respect to a quenching substrate. We find
      that the crystallite orientation distribution has little effect on the average
      exciton diffusion length. We suggest several possibilities for the lack of
      correlation between crystallographic texture and exciton transport in
      semicrystalline conjugated polymer films. 

PMID- 26292837
TI  - Sexual Behaviors and Transmission Risks Among People Living with HIV: Beliefs,
      Perceptions, and Challenges to Using Treatments as Prevention.
AB  - Antiretroviral therapy (ART) improves the health of people living with HIV and
      can reduce infectiousness, preventing HIV transmission. The potential preventive
      benefits of ART are undermined by beliefs that it is safe to have condomless sex
      when viral load is below levels of detection (infectiousness beliefs and risk
      perceptions). In this study, we hypothesized that infectiousness beliefs and HIV
      transmission risk perceptions would prospectively predict people living with HIV
      engaging in more condomless sex with HIV-negative and unknown HIV status sex
      partners. Sexually active HIV-positive men (n = 538, 76 %) and women (n = 166, 24
      %) completed computerized interviews of sexually transmitted infection (STI)
      symptoms and diagnoses, unannounced pill counts for medication adherence, medical
      chart-abstracted HIV viral load, and 28 daily cell-phone-delivered prospective
      sexual behavior assessments. Results showed that a total of 313 (44 %)
      participants had engaged in condomless sex with HIV-negative/unknown status sex
      partners, and these individuals demonstrated higher rates of STI symptoms and
      diagnoses. Two-thirds of participants who had condomless sex with HIV
      negative/unknown status partners had not disclosed their HIV status.
      Multivariable logistic regression models showed that beliefs regarding viral load
      and HIV infectiousness and perceptions of lower risk of HIV transmission
      resulting from HIV viral suppression predicted condomless sex with potentially
      uninfected partners over and above sex behaviors with HIV-positive partners and
      STI symptoms/diagnoses. Interventions that address HIV status disclosure and
      aggressively treat STI in sexually active people living with HIV should routinely
      accompany the use of HIV treatments as prevention.

PMID- 26292838
TI  - The Role of Facial and Body Hair Distribution in Women's Judgments of Men's
      Sexual Attractiveness.
AB  - Facial and body hair are some of the most visually conspicuous and sexually
      dimorphic of all men's secondary sexual traits. Both are androgen dependent,
      requiring the conversion of testosterone into dihydrotestosterone via the enzyme
      5alpha reductase 2 for their expression. While previous studies on the
      attractiveness of facial and body hair are equivocal, none have accounted as to
      how natural variation in their distribution may influence male sexual
      attractiveness. In the present study, we quantified men's facial and body hair
      distribution as either very light, light, medium, or heavy using natural
      photographs. We also tested whether women's fertility influenced their
      preferences for beards and body hair by comparing preferences among heterosexual
      women grouped according their fertility (high fertility, low fertility, and
      contraceptive use). Results showed that men with more evenly and continuously
      distributed facial hair from the lower jaw connecting to the mustache and
      covering the cheeks were judged as more sexually attractive than individuals with
      more patchy facial hair. Men with body hair were less attractive than when clean
      shaven, with the exception of images depicting some hair around the areolae,
      pectoral region, and the sternum that were significantly more attractive than
      clean-shaven bodies. However, there was no effect of fertility on women's
      preferences for men's beard or body hair distribution. These results suggest that
      the distribution of facial and body hair influences male attractiveness to women,
      possibly as an indication of masculine development and the synthesis of
      testosterone into dihydrotestosterone via 5alpha reductase. 

PMID- 26292839
TI  - Female-to-Male Transsexual Individuals Demonstrate Different Own Body
      Identification.
AB  - Transsexualism is characterized by feelings of incongruity between one's natal
      sex and one's gender identity. It is unclear whether transsexual individuals have
      a body image that is more congruent with their gender identity than their sex
      assigned at birth (natal sex) and, if so, whether there are contributions from
      perceptual dysfunctions. We compared 16 pre-hormone treatment female-to-male
      transsexual (FtM) individuals to 20 heterosexual female and 20 heterosexual male
      controls on a visual identification task. Participants viewed photographs of
      their own body that were morphed by different degrees to bodies of other females
      or males, and were instructed to rate "To what degree is this picture you?" We
      also tested global vs. local visual processing using the inverted faces task. FtM
      differed from both control groups in demonstrating higher self-identification
      ratings for bodies morphed to the sex congruent with their gender identity, and
      across a broad range of morph percentages. This difference was more pronounced
      for longer viewing durations. FtM showed reduced accuracy for upright faces
      compared with female controls for short duration stimuli, but no advantage for
      inverted faces. These results suggest different own body identification in FtM,
      consisting of a relatively diffuse identification with body images congruent with
      their gender identity. This is more likely accounted for by conscious, cognitive
      factors than perceptual differences.

PMID- 26292840
TI  - Correlates of a Single-Item Indicator Versus a Multi-Item Scale of Outness About
      Same-Sex Attraction.
AB  - In this study, we investigated if a single-item indicator measured the degree to
      which people were open about their same-sex attraction ("out") as accurately as a
      multi-item scale. For the multi-item scale, we used the Outness Inventory, which
      includes three subscales: family, world, and religion. We examined correlations
      between the single- and multi-item measures; between the single-item indicator
      and the subscales of the multi-item scale; and between the measures and
      internalized homonegativity, social attitudes towards homosexuality, and
      depressive symptoms. In addition, we calculated Tjur's R (2) as a measure of
      predictive power of the single-item indicator, multi-item scale, and subscales of
      the multi-item scale in predicting two health-related outcomes: depressive
      symptoms and condomless anal sex with multiple partners. There was a strong
      correlation between the single- and multi-item measures (r = 0.73). Furthermore,
      there were strong correlations between the single-item indicator and each
      subscale of the multi-item scale: family (r = 0.70), world (r = 0.77), and
      religion (r = 0.50). In addition, the correlations between the single-item
      indicator and internalized homonegativity (r = -0.63), social attitudes towards
      homosexuality (r = -0.38), and depression (r = -0.14) were higher than those
      between the multi-item scale and internalized homonegativity (r = -0.55), social
      attitudes towards homosexuality (r = -0.21), and depression (r = -0.13). Contrary
      to the premise that multi-item measures are superior to single-item measures, our
      collective findings indicate that the single-item indicator of outness performs
      better than the multi-item scale of outness.

PMID- 26292841
TI  - Osteogenic properties of a short BMP-2 chimera peptide.
AB  - Bone morphogenetic proteins (BMPs) play a key role in bone and cartilage
      formation. For these properties, BMPs are employed in the field of tissue
      engineering to induce bone regeneration in damaged tissues. To overcome drawbacks
      due to the use of entire proteins, synthetic peptides derived from their parent
      BMPs have come out as promising molecules for biomaterial design. On the
      structural ground of the experimental BMP-2 receptor complexes reported in the
      literature, we designed three peptides, reproducing the BMP-2 region responsible
      for the binding to the type II receptor, ActRIIB. These peptides were
      characterized by NMR, and the structural features of the peptide-receptor binding
      interface were highlighted by docking experiments. Peptide-receptor binding
      affinities were analyzed by means of ELISA and surface plasmon resonance
      techniques. Furthermore, cellular assays were performed to assess their
      osteoinductive properties. A chimera peptide, obtained by combining the sequence
      portions 73-92 and 30-34 of BMP-2, shows the best affinity for ActRIIB in the
      series and represents a good starting point for the design of new compounds able
      to reproduce osteogenic properties of the parent BMP-2.

PMID- 26292842
TI  - Cholesterol conjugation potentiates the antiviral activity of an HIV
      immunoadhesin.
AB  - Immunoadhesins are engineered proteins combining the constant domain (Fc) of an
      antibody with a ligand-binding (adhesion) domain. They have significant potential
      as therapeutic agents, because they maintain the favourable pharmacokinetics of
      antibodies with an expanded repertoire of ligand-binding domains: proteins,
      peptides, or small molecules. We have recently reported that the addition of a
      cholesterol group to two HIV antibodies can dramatically improve their antiviral
      potency. Cholesterol, which can be conjugated at various positions in the
      antibody, including the constant (Fc) domain, endows the conjugate with affinity
      for the membrane lipid rafts, thus increasing its concentration at the site where
      viral entry occurs. Here, we extend this strategy to an HIV immunoadhesin,
      combining a cholesterol-conjugated Fc domain with the peptide fusion inhibitor
      C41. The immunoadhesin C41-Fc-chol displayed high affinity for Human Embryonic
      Kidney (HEK) 293 cells, and when tested on a panel of HIV-1 strains, it was
      considerably more potent than the unconjugated C41-Fc construct. Potentiation of
      antiviral activity was comparable to what was previously observed for the
      cholesterol-conjugated HIV antibodies. Given the key role of cholesterol in lipid
      raft formation and viral fusion, we expect that the same strategy should be
      broadly applicable to enveloped viruses, for many of which it is already known
      the sequence of a peptide fusion inhibitor similar to C41. Moreover, the sequence
      of heptad repeat-derived fusion inhibitors can often be predicted from genomic
      information alone, opening a path to immunoadhesins against emerging viruses.

PMID- 26292843
TI  - "Am I Becoming a Serial Killer?" A Case Study of Cognitive Behavioral Therapy for
      Mental Illness Anxiety.
AB  - BACKGROUND: Although mental illness anxiety is described in the literature, there
      is very little information on which to draw when treating individuals who present
      with fears and worries about mental health. In fact, we identified no previous
      case descriptions focused on this form of anxiety and treated from a cognitive
      behavioral perspective. AIMS: The current case study aims to advance the
      understanding of the clinical picture of mental illness anxiety, and facilitate
      the understanding of how cognitive behavioral techniques for health anxiety can
      be effectively adapted and implemented for such a case. METHOD: A case study
      approach was adopted in which a baseline condition and repeated assessments were
      conducted during an 8-week treatment and 2-month follow-up period. In the current
      case study, we discuss the assessment, conceptualization, and cognitive
      behavioral treatment of a 24-year old woman who presented with mental illness
      anxiety. Several common health anxiety assessment tools and cognitive behavioural
      techniques were adapted for her particular clinical presentation. RESULTS:
      Consistent with research evidence for health anxiety, significant improvements in
      health anxiety and anxiety sensitivity were seen after eight sessions of therapy
      and maintained at 2-month follow-up. CONCLUSIONS: The results provide preliminary
      evidence that cognitive behavioral techniques for health anxiety can be
      effectively and efficiently adapted for mental illness anxiety. However, the lack
      of available research pertaining to mental illness anxiety contributes to
      challenges in conceptualization, assessment and treatment.

PMID- 26292844
TI  - Differential rates of phenotypic introgression are associated with male
      behavioral responses to multiple signals.
AB  - Sexual selection on multiple signals may lead to differential rates of signal
      introgression across hybrid zones if some signals contribute to reproductive
      isolation but others facilitate gene flow. Competition among males is one
      powerful form of sexual selection, but male behavioral responses to multiple
      traits have not been considered in a system where traits have introgressed
      differentially. Using playbacks, mounts, and a reciprocal experimental design, we
      tested the hypothesis that male responses to song and plumage in two subspecies
      of red-backed fairy-wren (Malurus melanocephalus) explain patterns of
      differential signal introgression (song has not introgressed, whereas plumage
      color has introgressed asymmetrically). We found that males of both subspecies
      discriminated symmetrically between subspecies' songs at a long range, but at a
      close range, we found that aggression was equal for both subspecies' plumage and
      songs. Taken together, our results suggest that male behavioral responses hinder
      the introgression of song, but allow for the observed asymmetrical introgression
      of plumage. Our results highlight how behavioral responses are a key component of
      signal evolution when recently divergent taxa come together, and how differential
      responses to multiple signals may lead to differential signal introgression and
      novel trait combinations. 

PMID- 26292845
TI  - Endoscopic posterior graft laryngotracheal reconstruction - our initial
      experience of surgical technique in six children.

PMID- 26292846
TI  - Systematic review on the use of matrix-bound sealants in pancreatic resection.
AB  - BACKGROUND: Pancreatic fistula is a potentially life-threatening complication
      after a pancreatic resection. The aim of this systematic review was to evaluate
      the role of matrix-bound sealants after a pancreatic resection in terms of
      preventing or ameliorating the course of a post-operative pancreatic fistula.
      METHODS: A systematic search was performed in the literature from May 2005 to
      April 2015. Included were clinical studies using matrix-bound sealants after a
      pancreatic resection, reporting a post-operative pancreatic fistula (POPF)
      according to the International Study Group on Pancreatic Fistula classification,
      in which grade B and C fistulae were considered clinically relevant. RESULTS: Two
      were studies on patients undergoing pancreatoduodenectomy (sealants n = 67,
      controls n = 27) and four studies on a distal pancreatectomy (sealants n = 258,
      controls n = 178). After a pancreatoduodenectomy, 13% of patients treated with
      sealants versus 11% of patients without sealants developed a POPF (P = 0.76), of
      which 4% versus 4% were clinically relevant (P = 0.87). After a distal
      pancreatectomy, 42% of patients treated with sealants versus 52% of patients
      without sealants developed a POPF (P = 0.03). Of these, 9% versus 12% were
      clinically relevant (P = 0.19). CONCLUSIONS: The present data do not support the
      routine use of matrix-bound sealants after a pancreatic resection, as there was
      no effect on clinically relevant POPF. Larger, well-designed studies are needed
      to determine the efficacy of sealants in preventing POPF after a
      pancreatoduodenectomy.

PMID- 26292847
TI  - Shells and Bones: A Forensic Medicine Study of the Association of Terrestrial
      Snail Allopeas micra with Buried Human Remains in Brazil.
AB  - Little is known regarding the scavenger fauna associated with buried human
      corpses, particularly in clandestine burials. We report the presence of 20 shells
      of the terrestrial snail Allopeas micra, within hollow bones of human remains
      buried for 5 years, during the process of collecting DNA material. The fact that
      a large number of shells of A. micra had been found in the corpse and in the
      crime scene supports the assumption that there was no attempt to remove the
      corpse from the area where the crime occurred. Despite this, our observations
      cannot be used to estimate the postmortem interval because there is no precise
      knowledge about the development of this species. This is the first record of a
      terrestrial snail associated with a human corpse and its role in this forensic
      medicine case. 

PMID- 26292850
TI  - Inducible Expression of Agrobacterium Virulence Gene VirE2 for Stringent
      Regulation of T-DNA Transfer in Plant Transient Expression Systems.
AB  - Agrotransfection with viral vectors is an effective solution for the transient
      production of valuable proteins in plants grown in contained facilities.
      Transfection methods suitable for field applications are desirable for the
      production of high-volume products and for the transient molecular reprogramming
      of plants. The use of genetically modified (GM) Agrobacterium strains for plant
      transfections faces substantial biosafety issues. The environmental biosafety of
      GM Agrobacterium strains could be improved by regulating their T-DNA transfer via
      chemically inducible expression of virE2, one of the essential Agrobacterium
      virulence genes. In order to identify strong and stringently regulated promoters
      in Agrobacterium strains, we evaluated isopropyl-beta-d-thiogalactoside-inducible
      promoters Plac, Ptac, PT7/lacO, and PT5/lacOlacO and cumic acid-inducible
      promoters PlacUV5/CuO, Ptac/CuO, PT5/CuO, and PvirE/CuO. Nicotiana benthamiana
      plants were transfected with a virE2-deficient A. tumefaciens strain containing
      transient expression vectors harboring inducible virE2 expression cassettes and
      containing a marker green fluorescent protein (GFP) gene in their T-DNA region.
      Evaluation of T-DNA transfer was achieved by counting GFP expression foci on
      plant leaves. The virE2 expression from cumic acid-induced promoters resulted in
      47 to 72% of wild-type T-DNA transfer. Here, we present efficient and tightly
      regulated promoters for gene expression in A. tumefaciens and a novel approach to
      address environmental biosafety concerns in agrobiotechnology. 

PMID- 26292849
TI  - Salsalate attenuates diet induced non-alcoholic steatohepatitis in mice by
      decreasing lipogenic and inflammatory processes.
AB  - BACKGROUND AND PURPOSE: Salsalate (salicylsalicylic acid) is an anti-inflammatory
      drug that was recently found to exert beneficial metabolic effects on glucose and
      lipid metabolism. Although its utility in the prevention and management of a wide
      range of vascular disorders, including type 2 diabetes and metabolic syndrome has
      been suggested before, the potential of salsalate to protect against non
      alcoholic steatohepatitis (NASH) remains unclear. The aim of the present study
      was therefore to ascertain the effects of salsalate on the development of NASH.
      EXPERIMENTAL APPROACH: Transgenic APOE*3Leiden.CETP mice were fed a high-fat and
      high-cholesterol diet with or without salsalate for 12 and 20 weeks. The effects
      on body weight, plasma biochemical variables, liver histology and hepatic gene
      expression were assessed. KEY RESULTS: Salsalate prevented weight gain, improved
      dyslipidemia and insulin resistance and ameliorated diet-induced NASH, as shown
      by decreased hepatic microvesicular and macrovesicular steatosis, reduced hepatic
      inflammation and reduced development of fibrosis. Salsalate affected lipid
      metabolism by increasing beta-oxidation and decreasing lipogenesis, as shown by
      the activation of PPAR-alpha, PPAR-gamma co-activator 1beta, RXR-alpha and
      inhibition of genes controlled by the transcription factor MLXIPL/ChREBP.
      Inflammation was reduced by down-regulation of the NF-kappaB pathway, and
      fibrosis development was prevented by down-regulation of TGF-beta signalling.
      CONCLUSIONS AND IMPLICATIONS: Salsalate exerted a preventive effect on the
      development of NASH and progression to fibrosis. These data suggest a clinical
      application of salsalate in preventing NASH.

PMID- 26292851
TI  - The Protective Effect of alpha-Hederin, the Active Constituent of Nigella sativa,
      on Lung Inflammation and Blood Cytokines in Ovalbumin Sensitized Guinea Pigs.
AB  - In the present study, the preventive effect of two different concentrations of
      alpha-hederin, the active constituent of Nigella sativa, on lung inflammation and
      blood cytokines in ovalbumin sensitized guinea pigs was examined. Forty eight
      male adult guinea pigs were divided into control (C), sensitized (S) and
      sensitized pretreated groups; with thymoquinone (S+TQ), low dose (S+LAH) and high
      dose of alpha-hederin (S+HAH) and inhaled fluticasone propionate (S+FP). The lung
      histopathology and blood levels of IL-4, IFN-gamma and IL-17 were assessed.
      Compared to sensitized animals, all pathological changes improved significantly
      in pretreated groups (p < 0.001 to p < 0.05). These improvements in alpha-hederin
      pretreated groups were similar to S+TQ and S+FP groups except cellular
      infiltration in S+LAH and S+HAH groups which was lower than S+TQ group (p <
      0.05). The blood IL-4 and IL-17 levels in S+HAH groups showed a significant
      decrease compared to S group (p < 0.05) which were similar to S+TQ and S+FP
      groups. The level of IFN-gamma in S+LAH and S+HAH groups increased significantly
      compared to S group (p < 0.05) which was higher than S+FP group (p < 0.05). Blood
      IL-4 in S+HAH group was significantly lower than S+LAH group (p < 0.05). In
      conclusion, alpha-hederin could attenuate the lung inflammation and improve the
      changes of cytokines like thymoquinone and fluticasone in used dosages.

PMID- 26292852
TI  - Neural correlates of reactive aggression in children with attention
      deficit/hyperactivity disorder and comorbid disruptive behaviour disorders.
AB  - OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is often linked with
      impulsive and aggressive behaviour, indexed by high comorbidity rates between
      ADHD and disruptive behaviour disorders (DBD). The present study aimed to
      investigate underlying neural activity of reactive aggression in children with
      ADHD and comorbid DBD using functional neuroimaging techniques (fMRI). METHOD:
      Eighteen boys with ADHD (age 9-14 years, 10 subjects with comorbid DBD) and 18
      healthy controls were administered a modified fMRI-based version of the 'Point
      Subtraction Aggression Game' to elicit reactive aggressive behaviour. Trials
      consisted of an 'aggression phase' (punishment for a fictitious opponent) and an
      'outcome phase' (presentation of the trial outcome). RESULTS: During the
      aggression phase, higher aggressive responses of control children were
      accompanied by higher activation of the ventral anterior cingulate cortex and the
      temporoparietal junction. Patients displayed inverted results. During the outcome
      phase, comparison between groups and conditions showed differential activation in
      the dorsal striatum and bilateral insular when subjects gained points. Losing
      points was accompanied by differential activation of regions belonging to the
      insula and the middle temporal sulcus. CONCLUSION: Data support the hypothesis
      that deficient inhibitory control mechanisms are related to increased impulsive
      aggressive behaviour in young people with ADHD and comorbid DBD.

PMID- 26292853
TI  - Re: Benefit in Regionalization of Care for Patients Treated with Nephrectomy: A
      Nationwide Inpatient Sample.

PMID- 26292854
TI  - Re: Significance of ERBB2 Overexpression in Therapeutic Resistance and Cancer
      Specific Survival in Muscle-Invasive Bladder Cancer Patients Treated with
      Chemoradiation-Based Selective Bladder-Sparing Approach.

PMID- 26292855
TI  - Re: Contemporary Cost-Effectiveness Analysis Comparing Sequential bacillus
      Calmette-Guerin and Electromotive Mitomycin versus bacillus Calmette-Guerin Alone
      for Patients with High-Risk Non-Muscle-Invasive Bladder Cancer.

PMID- 26292856
TI  - Re: Association between Cannabis Use and the Risk of Bladder Cancer: Results from
      the California Men's Health Study.

PMID- 26292857
TI  - Re: Yield of Urinary Tract Cancer Diagnosis with Repeat CT Urography in Patients
      with Hematuria.

PMID- 26292858
TI  - Re: Complications following Surgery with or without Radiotherapy or Radiotherapy
      Alone for Prostate Cancer.

PMID- 26292859
TI  - Re: Androgen Receptor Gene Aberrations in Circulating Cell-Free DNA: Biomarkers
      of Therapeutic Resistance in Castration-Resistant Prostate Cancer.

PMID- 26292860
TI  - Re: Randomized Clinical Trial of Brewed Green and Black Tea in Men with Prostate
      Cancer Prior to Prostatectomy.

PMID- 26292861
TI  - Re: Postoperative Radiation Therapy for Patients at High-Risk of Recurrence after
      Radical Prostatectomy: Does Timing Matter?

PMID- 26292862
TI  - Re: CMTM3 Inhibits Human Testicular Cancer Cell Growth through Inducing Cell
      Cycle Arrest and Apoptosis.

PMID- 26292863
TI  - Re: Urinary Incontinence and Erectile Dysfunction after Robotic versus Open
      Radical Prostatectomy: A Prospective, Controlled, Nonrandomised Trial.

PMID- 26292864
TI  - Re: Electrosurgical Management of Hunner Ulcers in a Referral Center's
      Interstitial Cystitis Population.

PMID- 26292865
TI  - Re: Urgency after a Sling: Review of the Management.

PMID- 26292866
TI  - Re: What is the Most Bothersome Lower Urinary Tract Symptom? Individual- and
      Population-Level Perspectives for both Men and Women.

PMID- 26292867
TI  - Re: Trigonal versus Extratrigonal Botulinum Toxin-A: A Systematic Review and Meta
      Analysis of Efficacy and Adverse Events.

PMID- 26292868
TI  - Re: Prevalence of Myofascial Chronic Pelvic Pain and the Effectiveness of Pelvic
      Floor Physical Therapy.

PMID- 26292869
TI  - Re: Role of Urodynamics before Prolapse Surgery.

PMID- 26292870
TI  - Re: The Impact of Obstructive Sleep Apnea Syndrome on Nocturnal Urine Production
      in Older Men with Nocturia.

PMID- 26292871
TI  - Re: Safety and Efficacy of Desmopressin for the Treatment of Nocturia in Elderly
      Patients: A Cohort Study.

PMID- 26292872
TI  - Re: Prevalence of Urinary Incontinence and Associated Factors in Nursing Home
      Residents.

PMID- 26292873
TI  - Re: Can Treatment of Nocturia Increase Testosterone Level in Men with Late Onset
      Hypogonadism?

PMID- 26292874
TI  - Re: Urinary Incontinence and Prevalence of High Depressive Symptoms in Older
      Black versus White Women.

PMID- 26292875
TI  - Re: Relationship between Benign Prostatic Hyperplasia/Lower Urinary Tract
      Symptoms and Total Serum Testosterone Level in Healthy Middle-Aged Eugonadal Men.

PMID- 26292876
TI  - Re: Insulin Resistance is an Independent Predictor of Severe Lower Urinary Tract
      Symptoms and of Erectile Dysfunction: Results from a Cross-Sectional Study.

PMID- 26292877
TI  - Re: Is Type-2 Diabetes Mellitus Associated with Overactive Bladder Symptoms in
      Men with Lower Urinary Tract Symptoms?

PMID- 26292878
TI  - Re: 5alpha-Reductase Type 1 Modulates Insulin Sensitivity in Men.

PMID- 26292879
TI  - Re: Graft and Patient Survival Outcomes of a Third Kidney Transplant.

PMID- 26292880
TI  - Re: Testosterone Products: Drug Safety Communication - FDA Cautions about Using
      Testosterone Products for Low Testosterone due to Aging; Requires Labeling Change
      to Inform of Possible Increased Risk of Heart Attack and Stroke.

PMID- 26292881
TI  - Re: Characteristics of Genitourinary Injuries Associated with Pelvic Fractures
      during Operation Iraqi Freedom and Operation Enduring Freedom.

PMID- 26292882
TI  - Re: Effects of Long-Term Androgen Replacement Therapy on the Physical and Mental
      Statuses of Aging Males with Late-Onset Hypogonadism: A Multicenter Randomized
      Controlled Trial in Japan (EARTH Study).

PMID- 26292883
TI  - Re: Surgical Correction of Persistent Peyronie's Disease following Collagenase
      Clostridium histolyticum Treatment.

PMID- 26292884
TI  - Re: Screening and Monitoring in Men Prescribed Testosterone Therapy in the U.S.,
      2001-2010.

PMID- 26292885
TI  - Re: Impact of Sperm Morphology on the Likelihood of Pregnancy after Intrauterine
      Insemination.

PMID- 26292886
TI  - Re: Delayed Postoperative Hematoma Formation after Inflatable Penile Prosthesis
      Implantation.

PMID- 26292887
TI  - Re: Alternative Placement of Penile Prosthesis Reservoir and AUS Pressure
      Regulating Balloon.

PMID- 26292889
TI  - Re: Increased Frequency of Aneuploidy in Long-Lived Spermatozoa.

PMID- 26292888
TI  - Re: Status of Sperm Morphology Assessment: An Evaluation of Methodology and
      Clinical Value.

PMID- 26292890
TI  - Re: Micro-Electrophoresis: A Noninvasive Method of Sperm Selection Based on
      Membrane Charge.

PMID- 26292891
TI  - Re: Analysis of Semen Parameters in Male Referrals: Impact of Reference Limits,
      Stratification by Fertility Categories, Predictors of Change, and Comparison of
      Normal Semen Parameters in Subfertile Couples.

PMID- 26292892
TI  - Re: Emotional and Behavioral Functioning in Children with Bladder Exstrophy
      Epispadias Complex: A Developmental Perspective.

PMID- 26292893
TI  - Re: Long-Term Fate of the Bladder after Isolated Bladder Neck Procedure.

PMID- 26292894
TI  - Re: Bladder Capacity as a Predictor of Voided Continence after Failed Exstrophy
      Closure.

PMID- 26292896
TI  - Re: TERT Promoter Mutations and Telomerase Reactivation in Urothelial Cancer.

PMID- 26292897
TI  - Re: SAHA Triggered MET Activation Contributes to SAHA Tolerance in Solid Cancer
      Cells.

PMID- 26292898
TI  - Re: Image-Guided Robot-Assisted Prostate Ablation Using Water Jet
      Hydrodissection: Initial Study of a Novel Technology for Benign Prostatic
      Hyperplasia.

PMID- 26292899
TI  - Re: A Human Prostatic Bacterial Isolate Alters the Prostatic Microenvironment and
      Accelerates Prostate Cancer Progression.

PMID- 26292900
TI  - Erratum.

PMID- 26292903
TI  - The clinical use of DNA methyltransferase inhibitors in myelodysplastic
      syndromes.
AB  - Myelodysplastic syndromes (MDS) include a heterogeneous group of acquired
      hematopoietic malignancies characterized by ineffective hematopoiesis, peripheral
      cytopenias, and a varying propensity for progression to acute myeloid leukemia.
      Patients with higher risk MDS have dismal outcomes and treatment options are very
      limited. Aside from allogeneic hematopoietic cell transplantation, the only
      potentially curative treatment, DNA methyltransferase inhibitors (DNMTIs) are the
      only intervention that prolongs overall survival in patients with higher risk
      MDS. The clinical use of DNMTIs in MDS was one of the earliest successful
      attempts at epigenetic reprogramming of cancer. In this review, we discuss the
      clinical use of DNMTIs in MDS highlighting the current challenges and
      controversies and future directions of research needed to explore the full
      therapeutic potential of these agents. 

PMID- 26292904
TI  - Complexity of NOTCH1 juxtamembrane insertion mutations in T-cell acute
      lymphoblastic leukemia.

PMID- 26292905
TI  - Author's response to a letter to the editor.

PMID- 26292906
TI  - Maxillary sinus volumes of patients with unilateral cleft lip and palate.
AB  - BACKGROUND AND OBJECTIVE: Studies about maxillary sinuses of cleft lip-palate
      patients have increased since sinusitis is commonly observed in these patients.
      It is evident that maxillary sinus will be morphologically affected in these
      patients. And anatomic differences may be a cause or at least a contributor of
      sinusitis. The aim of this study was to compare maxillary sinus volumes of the
      non-syndromic patients with unilateral cleft lip-palate and control group by
      using Cone-Beam computed tomography. METHODS: Tomography scans of 44 unilateral
      cleft lip-palate patients (18 right and 26 left) with age and gender matched 45
      control patients were evaluated for the study. The images used in the study were
      part of the diagnostic records collected due to dental treatment needs. All
      tomographs were obtained in supine position by using Cone-Beam computed
      tomography (NewTom 5G, QR, Verona, Italy). The patient-specific Hounsfield values
      were set to include the largest amount of voxels in the sinuses volume
      calculation individually. All data were measured in mm(3). RESULTS: There was no
      statistically difference between the gender and age distributions of the groups.
      No statistically significant difference was found on the cleft and non-cleft
      side, the right and left side of the unilateral cleft lip-palate patients and the
      control group (P>0.05). For the inter group comparison, mean maxillary sinus
      volumes volume of unilateral cleft lip-palate patients (9894.55+/-4171.44mm(3))
      was statistically smaller than the control group (11,977.90+/-4484.93mm(3))
      (P<0.05). CONCLUSION: Maxillary sinus volumes were effected negatively in
      unilateral cleft lip-palate patients when compared with the healthy control
      group. No difference was found on the cleft, non-cleft side and the right-left
      side of the unilateral cleft lip-palate patients.

PMID- 26292907
TI  - Outcomes variability in non-emergent esophageal foreign body removal: Is daytime
      removal better?
AB  - OBJECTIVE: The objective of this study is to investigate differences between
      esophageal foreign body removal performed during standard operating room hours
      and those performed after-hours in asymptomatic patients. METHODS: A
      retrospective chart review at a tertiary children's hospital identified 264 cases
      of patients with non-emergent esophageal foreign bodies between 2006 and 2011.
      Variables pertaining to procedure and recovery times, hospital charges,
      complications, length of stay, American Society of Anesthesiology (ASA)
      classification, and presence of mucosal injury were summarized and compared
      between cases performed during standard operating hours and those performed after
      hours. RESULTS: Cases performed during standard hours had significantly longer
      average wait times compared with after-hours cases (13.1h versus 9.0h, p<0.001).
      No other clinical characteristics or outcomes were significantly different
      between groups. Longer wait times are not associated with mucosal injury or
      postoperative complications. CONCLUSION: There were no significant differences in
      procedure time, charges, or safety in after-hours removal of non-emergent
      esophageal foreign bodies compared to removal during standard operating hours. OR
      wait time was about 4h longer during standard hours compared with after-hours.
      This study could not assess the factors to determine the impact in differences in
      hospital resource utilization or work force, which may be significant between
      these two groups.

PMID- 26292908
TI  - Point of care susceptibility testing in primary care - does it lead to a more
      appropriate prescription of antibiotics in patients with uncomplicated urinary
      tract infections? Protocol for a randomized controlled trial.
AB  - BACKGROUND: Urinary tract infection (UTI) is a common infection in primary care
      and is the second leading reason for prescription of antibiotics in Denmark. The
      diagnosis is often based on symptoms and urine dip-stick, which has limited
      validity, causing the risk of unnecessary antibiotic prescription. Additionally,
      with increasing antibiotic resistance, the risk of choosing an antibiotic to
      which an infecting pathogen is resistant is rising. Combined point-of-care-tests
      (POCT) for urine culture and susceptibility testing have been developed and
      validated for primary care, and performing such a test in all patients with
      suspected UTI in primary care seems rational in order to reduce the use of
      inappropriate antibiotics. However, the clinical effect of the culture and
      susceptibility test has not yet been investigated. This study aims to investigate
      whether POCT urine culture and susceptibility testing decreases the inappropriate
      use of antibiotics and leads to faster patient recovery. METHODS/DESIGN:
      Randomized controlled open label trial of two diagnostic approaches. 750 patients
      with symptoms of uncomplicated UTI, consecutively contacting their general
      practitioner (GP), randomized to either POCT urine culture and susceptibility
      testing and targeted treatment or POCT urine culture without susceptibility
      testing and empirical treatment. Treatment is started when the POCT is read. The
      two groups are compared with regard to appropriate choice of antibiotics,
      clinical remission, and microbiological cure rates. DISCUSSION: The results of
      this study may provide important evidence to recommend POCT culture and
      susceptibility testing in all patients with suspected uncomplicated UTI. This
      could become an additional strategy to fight antibiotic resistance. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT02323087 .

PMID- 26292909
TI  - Antiepileptic drug withdrawal in medically and surgically treated patients: a
      meta-analysis of seizure recurrence and systematic review of its predictors.
AB  - AIM: Many seizure-free patients consider withdrawal of antiepileptic drugs, both
      when seizure control is achieved by medication alone, or once they became seizure
      free following epilepsy surgery. The risk of recurrence is consequently of very
      important prognostic value. However, estimations of recurrence risks are outdated
      for both populations. In addition, although many publications have reported
      predictors of seizure relapse, no comprehensive overview of prognostic factors is
      available. METHODS: A systematic review of the databases of PubMed and EMBASE was
      conducted, identifying articles on antiepileptic drug withdrawal in patient
      cohorts. Recurrence risk meta-analyses were performed for both populations at
      one, two, three to four, and five or more years of follow-up. Within the selected
      articles, studies presenting multivariable analysis of predictors were
      identified; all studied predictors were listed, as well as all significant
      independent predictors. The quality of separate analyses of predictors was
      assessed. RESULTS: There was no significant difference of long-term cumulative
      recurrence risk between surgical and medication-only populations, with
      respectively 29% and 34% recurrences. In medication-only treated patients, 25
      factors have been reported as significant independent predictors; 12 have been
      reported in surgical cohorts. The quality of most analyses of predictors was low
      to moderate. No predictor was consistently found among all analyses, and for most
      predictors, study results were contradictory. CONCLUSION: No consistent set of
      predictors could be identified because a large number of variables have been
      identified in the literature, many studies reported contradicting results, study
      populations varied considerably, and the quality of the original studies was
      often low. Meta-analysis of individual participant data is necessary, because it
      allows for (1) correction for differences in follow-up duration between subjects
      and studies, (2) a study of interaction effects, (3) calculation of more accurate
      estimates valid across several populations, and (4) the assessment of each
      predictor's effect size.

PMID- 26292910
TI  - Children and adolescents who stutter: Further investigation of anxiety.
AB  - PURPOSE: Despite the greatly increased risk of social anxiety disorder in adults
      who stutter, there is no clear indication of the time of onset of this disorder
      in childhood and adolescence. The purpose of this study was to explore this issue
      further using the Revised Children's Manifest Anxiety Scale (RCMAS), so that
      appropriate interventions can be developed prior to adulthood. This is the first
      time the RCMAS has been completed by children younger than 11 years. Using the
      same test for both school-age children and adolescents can potentially identify
      when anxiety starts to develop from age 6 years through to adulthood. METHODS:
      The RCMAS was administered to 18 school-age boys, five school-age girls, 41
      adolescent boys and nine adolescent girls who were seeking treatment for their
      stuttering. Participants also rated the severity of their own stuttering.
      RESULTS: All mean scaled scores on the four RCMAS subscales and Total Anxiety
      scores were within normal limits. However, for both groups of boys, scores on the
      Lie Scale were significantly higher than scores on the other three subscales.
      CONCLUSIONS: Experts suggest high scores on the RCMAS Lie Scale are indicative of
      participants attempting to present themselves in a positive light and so cast
      doubt on the veracity of their other responses on the test. One interpretation,
      then, is that the boys were concealing true levels of anxiety about their
      stuttering. The results suggest why findings of anxiety studies in children and
      adolescents to date are equivocal. Clinical implications are discussed.
      EDUCATIONAL OBJECTIVES: The reader will be able to: (a) discuss why understanding
      when anxiety starts in people who stutter is important, (b) describe the function
      of the RCMAS Lie sub scale and (c) summarize the possible implications of the
      RCMAS findings in this study.

PMID- 26292911
TI  - Predictive factors for conservative treatment failure in grade IV pediatric blunt
      renal trauma.
AB  - BACKGROUND: Most children with grade IV renal injury are treated using a
      conservative approach with a high success rate. However, a small minority of
      patients with grade IV renal injury require urological intervention because of
      symptomatic urinomas. The challenge lies in predicting which of the patients
      receiving initial conservative treatment may require delayed interventional
      management because of urological complications. OBJECTIVE: To identify clinical
      factors and radiological features associated with the need for urological
      intervention in grade IV pediatric, blunt renal trauma patients who were
      initially treated with a conservative approach. STUDY DESIGN: The medical records
      of consecutive 26 children presenting to our center between 1996 and 2014 with
      grade IV renal injury, were retrospectively reviewed. Clinical factors,
      radiological features on computed tomography (CT), use of urological
      intervention, and patient outcomes were analyzed. RESULTS: The population
      algorithm of this study is shown in the figure. The patients who required
      urological intervention had a higher transfusion rate and larger perinephric
      hematomas (>2.2 cm) than those who did not require intervention. The main
      laceration was located in the antero-medial portion of the kidney, and
      intravascular contrast extravasation was observed more often in patients who
      underwent urological intervention compared with patients with successful
      conservative management. DISCUSSION: The authors recommend the use of cautious
      observation and timely imaging studies for unresolved or expanding urinomas in
      children with grade IV renal trauma with predictive factors. Moreover, most
      patients received urological intervention 4-8 days after the trauma. Therefore,
      it is suggested that a follow-up image study for early detection of urological
      complications should be conducted 4-5 days after trauma in grade IV renal trauma
      children with predictive factors. If none of these factors are observed on the
      initial CT or during the clinical course, follow-up imaging study may be avoided
      during hospitalization. CONCLUSION: The need for transfusion, and the presence of
      specific image features on initial CT, such as the main laceration location in
      the antero-medial portion of kidney, intravascular contrast extravasation, and a
      large perinephric hematoma, served as useful predictive factors for urological
      intervention in grade IV pediatric blunt renal trauma patients who were initially
      treated with a conservative approach. The findings indicate that early detection
      and appropriate intervention should be considered a priority in the conservative
      treatment of grade IV pediatric renal trauma with predictive factors.

PMID- 26292913
TI  - Smoking and morphology of calcific deposits affect the outcome of needle
      aspiration of calcific deposits (NACD) for calcific tendinitis of the rotator
      cuff.
AB  - INTRODUCTION: Although NACD has proven to be an effective minimal invasive
      treatment for calcific tendinitis of the rotator cuff, little is known about the
      factors associated with treatment failure or the need for multiple procedures.
      METHODS: Patients with symptomatic calcific tendinitis who were treated by NACD
      were evaluated in a retrospective cohort study. Demographic details, medical
      history, sonographic and radiographic findings were collected from patient files.
      Failure of NACD was defined as the persistence of symptoms after a follow-up of
      at least six months. NACD procedures performed within six months after a previous
      NACD procedure were considered repeated procedures. Multivariate logistic
      regression analysis was used to determine factors associated with treatment
      failure and multiple procedures. RESULTS: 431 patients (277 female; mean age
      51.4+/-9.9 years) were included. Smoking (adjusted odds ratio (AOR): 1.7, 95% CI
      1.0-2.7, p=0.04) was significantly associated with failure of NACD. Patients with
      Gartner and Heyer (GH) type I calcific deposits were more likely to need multiple
      NACD procedures (AOR: 3.4, 95% CI 1.6-7.5, p<0.01) compared to patients with type
      III calcific deposits. Partial thickness rotator cuff tears were of no influence
      on the outcome of NACD or the number of treatments necessary. CONCLUSION: Smoking
      almost doubled the chance of failure of NACD and the presence of GH type I
      calcific deposits significantly increased the chance of multiple procedures.
      Partial thickness rotator cuff tears did not seem to affect the outcome of NACD.
      Based on the findings in this study, the importance of quitting smoking should be
      emphasized prior to NACD and partial thickness rotator cuff tears should not be a
      reason to withhold patients NACD.

PMID- 26292912
TI  - Nadir creatinine in posterior urethral valves: How high is low enough?
AB  - INTRODUCTION: Large retrospective studies of people with posterior urethral
      valves (PUV) have reported chronic renal insufficiency (CRI) in up to one third
      of the participants and end-stage renal failure in up to one quarter of them.
      Nadir creatinine (lowest creatinine during the first year following diagnosis) is
      the recognised prognostic indicator for renal outcome in PUV, the most commonly
      used cut-off being 1 mg/dl (88.4 umol/l). OBJECTIVE: To conduct a statistical
      analysis of nadir creatinine in PUV patients in order to identify the optimal cut
      off level as a prognostic indicator for CRI. STUDY DESIGN: Patients treated by
      endoscopic valve ablation at the present institution between 1993 and 2004 were
      reviewed. Chronic renal insufficiency was defined as CKD2 or higher. Statistical
      methods included receiver operating characteristic (ROC) curve analysis, Fisher
      exact test and diagnostic utility tests. Statistical significance was defined as
      P < 0.05. RESULTS AND DISCUSSION: Nadir creatinine was identified in 96 patients.
      The median follow-up was 9.4 (IQR 7.0, 13.4) years. A total of 29 (30.2%)
      patients developed CRI, with nine (9.4%) reaching end-stage renal failure. On ROC
      analysis, Nadir creatinine was highly prognostic for future CRI, with an Area
      Under the Curve of 0.887 (P < 0.001). Renal insufficiency occurred in all 10
      (100%) patients with nadir creatinine >88.4 umol/l compared with 19 of 86 (22.2%)
      patients with lower nadir creatinine (P < 0.001). As a test for future CRI, a
      nadir creatinine cut-off of 88.4 umol/l gave a specificity of 100%, but poor
      sensitivity of 34.5%. Lowering the cut-off to 75 umol/l resulted in improvement
      in all diagnostic utility tests (Table). All 14 (100%) patients with nadir
      creatinine >75 umol/l developed CRI, compared with 15 of 82 (18.3%) patients with
      lower nadir creatinine (P < 0.001). Sensitivity only approached 95% at 35 umol/l,
      at which level specificity was low (Table). Two out of 36 (5.6%) patients with
      nadir creatinine <35 umol/l developed CRI. Multivariate analysis found recurrent
      UTI (OR 4.733; CI 1.297-17.280) and nadir creatinine >75 umol/l (OR 48.988; CI
      4.9-490.11) to be independent risk factors for progression to CRI. Using cut-off
      values of 35 umol/l and 75 umol/l, patients can be stratified into low-,
      intermediate- and high-risk groups, with development of CRI in 5.3%, 28.3% and
      100%, respectively (P <0.001). The stage of CKD was higher in higher risk groups.
      CONCLUSION: Patients with nadir creatinine >75 umol/l (0.85 mg/dl) should be
      considered at high risk for CRI, while patients with nadir creatinine <=35 umol/l
      (0.4 mg/dl) should be considered low risk. Patients with nadir creatinine between
      these two values have an intermediate risk of CRI.

PMID- 26292915
TI  - The Treachery of Images.

PMID- 26292914
TI  - Comparison of the Diagnostic Performances of Three Techniques of ROI Placement
      for ADC Measurements in Pancreatic Adenocarcinoma.
AB  - RATIONALE AND OBJECTIVES: To prospectively investigate and compare three
      techniques of region of interest (ROI) placement for apparent diffusion
      coefficient (ADC) measurements in patients with pancreatic ductal adenocarcinoma
      (PDAC). MATERIALS AND METHODS: Twenty-one patients with surgical pathology-proven
      PDAC and 18 healthy volunteers were included. Respiratory-triggered single-shot
      echo-planar diffusion-weighted imaging (b values = 0, 600 s/mm(2)) was used to
      calculate the ADC maps across all participants. Three readers independently
      measured the ADCs according to three ROI methods: whole-volume, single-slice, and
      small solid samples of tumor. Mean ADCs for the healthy pancreas were calculated
      using three measurements from pancreatic head to tail, and ADCs of distal
      pancreas to the tumor were also measured. The interobserver variability for the
      three techniques was measured using the interclass correlation coefficient. The
      diagnostic performances were calculated and compared using the receiver operating
      characteristic curves (ROC). RESULTS: All the ADCs measured from the three ROI
      placements on PDAC were significantly lower than that from the normal pancreas.
      ADCs of solid tumor samples were significantly lower than that measured from
      whole volume or single slice (both P < .001). Only the ADCs measured from the
      solid sample ROI placements on tumor were observed significantly lower than the
      ADC of distal pancreatic parenchyma (P = .005). Areas under the ROC for the
      identification of PDAC, based on small solid samples, single-slice and whole
      volume ROIs, respectively, were 0.939, 0.791, and 0.735. CONCLUSIONS: ADC based
      on the small solid samples of tumor provided the highest diagnostic performance
      in assessing PDAC and was more accurate than ADCs measured from single-slice or
      whole-volume ROI.

PMID- 26292916
TI  - Adaptive Tutorials Versus Web-Based Resources in Radiology: A Mixed Methods
      Comparison of Efficacy and Student Engagement.
AB  - RATIONALE AND OBJECTIVES: Diagnostic imaging is under-represented in medical
      curricula globally. Adaptive tutorials, online intelligent tutoring systems that
      provide a personalized learning experience, have the potential to bridge this
      gap. However, there is limited evidence of their effectiveness for learning about
      diagnostic imaging. MATERIALS AND METHODS: We performed a randomized mixed
      methods crossover trial to determine the impact of adaptive tutorials on
      perceived engagement and understanding of the appropriate use and interpretation
      of common diagnostic imaging investigations. Although concurrently engaged in
      disparate blocks of study, 99 volunteer medical students (from years 1-4 of the 6
      year program) were randomly allocated to one of two groups. In the first arm of
      the trial on chest X-rays, one group received access to an adaptive tutorial,
      whereas the other received links to an existing peer-reviewed Web resource. These
      two groups crossed over in the second arm of the trial, which focused on computed
      tomography scans of the head, chest, and abdomen. At the conclusion of each arm
      of the trial, both groups completed an examination-style assessment, comprising
      questions both related and unrelated to the topics covered by the relevant
      adaptive tutorial. Online questionnaires were used to evaluate student
      perceptions of both learning resources. RESULTS: In both arms of the trial, the
      group using adaptive tutorials obtained significantly higher assessment scores
      than controls. This was because of higher assessment scores by senior students in
      the adaptive tutorial group when answering questions related to topics covered in
      those tutorials. Furthermore, students indicated significantly better engagement
      with adaptive tutorials than the Web resource and rated the tutorials as a
      significantly more valuable tool for learning. CONCLUSIONS: Medical students
      overwhelmingly accept adaptive tutorials for diagnostic imaging. The tutorials
      significantly improve the understanding of diagnostic imaging by senior students.

PMID- 26292917
TI  - Professionalism: Intent is Definitive.

PMID- 26292918
TI  - Reflective Writing: A Potential Tool to Improve Interprofessional Teamwork with
      Radiologists.
AB  - RATIONALE AND OBJECTIVES: Studies show that problems with interprofessional
      collaboration can result in adverse patient outcomes. These problems are common
      in the field of radiology, where technology has decreased opportunities for
      direct communication and collaboration with referring physicians. To our
      knowledge, critical reflection has not been studied as an intervention to better
      understand one's own and/or others' roles in the context of an interprofessional
      team, or more specifically, to improve interprofessional collaboration between
      radiologists and other physicians. MATERIALS AND METHODS: We trialed a reflective
      journaling assignment in our fourth year medical student general radiology
      elective. Student journal content was scored by percentage of comments reflecting
      on elective experiences versus recounting events. Content was categorized as
      "reflection" using an established measurement tool. Reflective content was
      evaluated to identify common themes. RESULTS: A total of 31 journals (178 entries
      and 26,749 words) were analyzed. Reflective content accounted for 43% of overall
      content and was subdivided into three categories: insight into one's own role and
      responsibilities as an ordering physician (20%), insight into a radiologist's
      role and responsibilities (12%), and thoughts on improving interprofessional
      collaboration with radiologists (11%). CONCLUSIONS: Reflective writing allows
      students to explore their own role and responsibilities in the context of an
      interprofessional team and may improve interprofessional teamwork with
      radiologists.

PMID- 26292919
TI  - Intensive care nurses' self-reported practice of intravenous fluid bolus therapy.
AB  - OBJECTIVE: To describe self-reported practice of fluid bolus therapy by intensive
      care nurses. RESEARCH METHODOLOGY: Multi-choice questionnaire of intensive care
      nurses conducted in July, 2014. SETTING: Major university tertiary referral
      centre. FINDINGS: 141 (64%) intensive care nurses responded. The majority of
      respondents identified 4% albumin as the commonest fluid bolus type and stated a
      fluid bolus was 250ml; however fluid bolus volume varied from 100ml to 1000ml.
      Hypotension was identified as the primary physiological trigger for a fluid
      bolus. In the hour following a fluid bolus for hypotension almost half of
      respondents expected an 'increase in mean arterial pressure of 0-10mmHg'; for
      oliguria, >60% expected an 'increase in urinary output of '0.5-1ml/kg/hour'; for
      low CVP, 50% expected 'an increase in CVP of 3-4mmHg'; and, for tachycardia, 45%
      expected a 'decrease in heart rate of 11-20beats/minute'. Finally, 7-10% of
      respondents were 'unsure' about the physiological response to a fluid bolus.
      CONCLUSION: Most respondents identified fluid bolus therapy to be at least 250ml
      of 4% albumin given as quickly as possible; however, volumes from 100 to 1000ml
      were also accepted. There was much uncertainty about the expected physiological
      response to fluid bolus therapy according to indication.

PMID- 26292920
TI  - Clinical management for patients admitted to a critical care unit with severe
      sepsis or septic shock.
AB  - BACKGROUND: The Surviving Sepsis Campaign promotes the use of norepinephrine as
      the first-line inotropic support for patients presenting with severe sepsis or
      septic shock in cases of persistent hypotension, despite adequate fluid
      resuscitation. However, there is little published evidence on how much
      noradrenaline is administered to such patients when admitted to the intensive
      care unit (ICU). The authors report the clinical management of this group of
      patients, with a special focus on the total amount and duration of norepinephrine
      infusion required. METHODS: A chart review of the admission records of an ICU in
      Hong Kong was carried out in 2013. A total of 5000 patients were screened by
      their diagnosis of severe sepsis or septic shock (in the admissions book) between
      1 January 2011 and 31 December 2013. A total of 150 of these were identified and
      100 included in the study after simultaneous in-depth reviews of their case notes
      by two of the investigators. The analysis covers those with severe sepsis or
      septic shock who required ICU admission for further care. Clinical management and
      outcomes were analysed. RESULTS: 100 patients (median age 61.6; M/F ratio 2:1)
      met the inclusion criteria. The mean ICU stay was 13.4 days (range=1-371). 14
      patients (14%) died in the ICU, with a 28-day mortality rate of 22%. The mean
      period of mechanical ventilation was 6.1 days (range=0-137). 91.5% (n=43) of
      patients had been operated on immediately before admission to the ICU, and the
      majority of these operations had been of the emergency type (97.7%, n=43). The
      mean total volumes of crystalloid and colloid administered were 3420ml and 478ml,
      respectively. The mean wean-off period for norepinephrine infusion was
      4234minutes (70.5hours). All patients were prescribed norepinephrine for
      persistent hypotension despite adequate fluid resuscitation, and the mean total
      amount administered was 87,211mg. Final multiple linear and logistic regression
      analysis showed different clinical outcomes associated with different covariates,
      which included: (1) total amount of crystalloid given, positively associated with
      the total amount and duration of norepinephrine infusion; (2) duration of
      mechanical ventilation, positively associated with the type of operation the
      patient had undergone; (3) 28-day mortality rate, positively associated with the
      INR. CONCLUSIONS: What this study adds to knowledge about patients suffering from
      severe sepsis or septic shock: (1) the mean duration of norepinephrine infusion
      for septic shock patients in an ICU is almost three days; (2) the more
      crystalloid is required to correct hypoperfusion, the higher the dosage and
      longer the duration of norepinephrine infusion will be necessary; (3) the longer
      the patient's INR, the higher the chances of death within 28 days. Since not all
      patients have their body weight measured on or after admission to the ICU, we
      suggest further research into indirect estimation of body weight by other means,
      such as anthropometric measures, to guide the use of drugs and nutritional
      support in the ICU. In addition, APACHE scores should be included in further
      studies to compare the severity of the patient's condition in other research.
      Furthermore, since this study does not cover university hospital ICUs, we suggest
      that further research concerning such patients should compare and reflect
      similarities and differences between public and university hospitals in the
      territory.

PMID- 26292921
TI  - Eosinophilia--A rare possible adverse reaction during anti-tumor necrosis factor
      alpha therapy for psoriasis.
AB  - The current use of tumor necrosis factor (TNF)-alpha inhibitors in
      rheumatological, dermatological and gastroenterological diseases has increased
      considerably in recent years. Different reports have been communicated regarding
      specific risks and side effects during treatment with TNF-alpha inhibitors.
      Eosinophilia has been linked to TNF-alpha inhibitors by several recent reports,
      although it is not listed as a possible adverse reaction in the product
      information of the drug. The aim of the present study was to evaluate the
      eosinophil count in patients diagnosed with psoriasis and treated with
      adalimumab. Based on the results of the present study, eosinophilia remains a
      rare adverse reaction during psoriasis treatment with TNF-alpha antagonists.

PMID- 26292922
TI  - Preparation, characterization, and phosphate removal and recovery of magnetic
      MnFe2O4 nano-particles as adsorbents.
AB  - Phosphate removal is an important method for controlling eutrophication in bodies
      of water. Adsorption is an effective phosphate removal approach. In this
      research, the adsorbent, namely, MnFe2O4, was prepared through the improved co
      precipitation method and investigated in terms of phosphate removal. MnFe2O4 was
      characterized by scanning electron microscopy, vibrating sample magnetometry, X
      ray diffraction, and Fourier transform infrared spectroscopy. Phosphate
      adsorption by MnFe2O4, desorption of adsorbed MnFe2O4 with the regeneration of
      desorbed MnFe2O4, and phosphate recovery were researched. Experimental results
      showed that adding the appropriate amount of polyethylene glycol to MnFe2O4
      precursors during preparation inhibited the agglomeration of MnFe2O4 between
      particles because of the magnetic property of MnFe2O4 etc. High crystallinity and
      strong magnetism were achieved by MnFe2O4 at low temperatures. Average particle
      size was 5.1 nm. The hysteresis loops confirmed the ferrimagnetic behaviour of
      MnFe2O4 with a high saturation magnetization (i.e. 26.27 emu/g). The adsorption
      mechanism of phosphate was mainly physical. The prepared MnFe2O4 had a spinel
      structure. The proposed technique achieved a phosphate removal rate of 96.06%. A
      considerable amount of phosphate was desorbed from the adsorbed MnFe2O4 in 15
      w/v% NaOH solution. The adsorption capacity of the desorbed MnFe2O4 could be
      restored to 96.73% in 10 w/v% NaNO3 solution through ion exchange. A sustainable
      phosphate source was recovered via hydroxyapatite crystallization in the
      desorption solution, which contained an abundant amount of phosphate as seed for
      suitable recovery condition. This finding suggested that MnFe2O4 could be a
      promising adsorbent for efficient phosphate removal. 

PMID- 26292923
TI  - Early investigational beta3 adreno-receptor agonists for the management of the
      overactive bladder syndrome.
AB  - INTRODUCTION: Antimuscarinic drugs form the mainstay of medical treatment for
      Overactive bladder Syndrome (OAB). With a proven efficacy but poor tolerability,
      other treatment modalities have been sought. Recent concerns regarding cumulative
      anticholinergic load and risk of dementia have provided further impetus to find
      novel OAB treatments. beta3-adrenoceptor (beta3-AR) agonists improve OAB symptoms
      by relaxing bladder tissue. As such, the search is underway to develop beta3-AR
      agonist drugs for the treatment of OAB. AREAS COVERED: The authors discuss
      studies on the only approved beta3-AR agonist, mirabegron, followed by reports on
      beta3-AR agonists in development, namely ritobegron and solabegron. The authors
      also discuss the early investigations of novel and putative beta3-AR agonist
      drugs which are being assessed for management of OAB, including
      aryloxypropanolamine, TRK-380, AJ-9677, BRL37344 and CL 316,243. These
      investigations have also highlighted alternative unexpected modes of beta3-AR
      action. EXPERT OPINION: There are a number of beta3-ARs in the pipeline but it is
      uncertain which, if any, will come to market and aid in the management of OAB. A
      picture of a beta3-AR dual action which was unknown previously is emerging.
      Overall, the authors believe that it is an exciting time for the pharmacological
      management of OAB with new drugs on the horizon which could potentially improve
      the patient's quality of life.

PMID- 26292925
TI  - An unusual cause of aggression and anxiety in a patient with Down syndrome.

PMID- 26292926
TI  - Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS)
      development after Amanita phalloides intoxication.

PMID- 26292927
TI  - Warfarin prophylaxis in migraine without aura but not in primary exercise
      headache.

PMID- 26292928
TI  - Framingham Risk Scores for coronary heart disease in a cohort of Saudi Arabian
      men and women with spinal cord injury.
AB  - People with spinal cord injury (SCI) are at increased risk of developing coronary
      heart disease (CHD). This study aimed at predicting CHD risk in a cohort of Saudi
      patients with SCI in comparison with patients without SCI and to correlate
      different demographic and clinical factors with Framingham Risk Score (FRS) in
      SCI patients. The study was conducted at the rehabilitation and the main
      hospitals of King Fahad Medical City, Riyadh, Saudi Arabia; on sixty patients
      with SCI and sixty controls of age >=20 years. FRS was calculated on a web-based
      calculator. For the SCI group, sub-groups were made for statistical analysis
      based on gender, cigarette smoking, neurological level and completeness of
      injury. The mean FRS for the SCI group (2 +/- 7.9) was significantly higher (P <
      0.001) than the control group (-2.24 +/- 3.4). The 10-year risk of developing CHD
      was low in 90 % of the SCI group and 100 % of the controls. The age, systolic
      blood pressure (SBP) and serum total cholesterol had a positive correlation to
      FRS in SCI patients and females had a significantly higher mean FRS than males (P
      = 0.03). There was no significant relation of resultant FRS with time since SCI,
      smoking history and neurological level or completeness of injury. Our sample of
      Saudi patients with SCI had a higher FRS as compared to controls, however,
      majority had a low risk of developing CHD in next 10 years. The age, SBP and
      total cholesterol surfaced as positive predictors of CHD in SCI patients. Time
      since SCI, smoking, and neurological level or completeness of injury did not
      influence the resultant FRS and thus the development of CHD. 

PMID- 26292929
TI  - Treatment of cauda equina syndrome caused by lumbar disc herniation with
      percutaneous endoscopic lumbar discectomy.
AB  - To evaluate the feasibility and clinical efficacy of percutaneous endoscopic
      lumbar discectomy (PELD) for cauda equina syndrome (CES) caused by disc
      herniation. 16 patients with CES caused by LDH at the early and middle stages of
      Shi's classification were selected as the objects of study, who underwent PELD.
      Clinical outcomes were assessed using the Macnab criteria and the visual analogue
      scale (VAS). The VAS for leg pain and back pain significantly decreased from
      preoperative scores of 7.67 +/- 1.23 and 7.52 +/- 1.42, respectively, to
      postoperative scores of 1.71 +/- 0.53 and 3.18 +/- 0.72. Thirteen patients showed
      favorable results. Complications included one patient of motor weakness, and one
      patient developed an ipsilateral recurrent herniation who finally acquired
      satisfactory result after reoperation. Hence, PELD could be used as an
      alternative surgical method for the treatment of CES in properly selected cases
      and appropriate patient selection and a reasonable surgical approach will give
      rise to better outcomes. 

PMID- 26292930
TI  - Topical Niosome Gel of Zingiber cassumunar Roxb. Extract for Anti-inflammatory
      Activity Enhanced Skin Permeation and Stability of Compound D.
AB  - An extract of Zingiber cassumunar Roxb. (ZC) was encapsulated in niosomes of
      which a topical gel was formed. (E)-4-(3',4'-dimethoxyphenyl)but-3-en-1-ol or
      compound D detected by a gradient HPLC was employed as the marker and its
      degradation determined to follow zero-order kinetics. Niosomes significantly
      retarded thermal-accelerated decomposition of compound D in the gel (p < 0.05)
      but did not change the activation energy of compound D. Niosomes enhanced in
      vitro permeation rate of compound D from the gel. Topical applications of ZC
      noisome gel gave a faster change in tail flick latency than piroxicam gel and
      hydrocortisone cream (p < 0.05) while there were insignificant differences in
      anti-inflammatory activity up to 6 h using croton oil-induced ear edema model in
      mice (p > 0.05). Thus, encapsulation of ZC extract in niosomes enhanced chemical
      stability and skin permeation with comparable topical anti-inflammatory effects
      to steroid and NSAID. 

PMID- 26292924
TI  - Large-scale RNA-Seq Transcriptome Analysis of 4043 Cancers and 548 Normal Tissue
      Controls across 12 TCGA Cancer Types.
AB  - The Cancer Genome Atlas (TCGA) has accrued RNA-Seq-based transcriptome data for
      more than 4000 cancer tissue samples across 12 cancer types, translating these
      data into biological insights remains a major challenge. We analyzed and compared
      the transcriptomes of 4043 cancer and 548 normal tissue samples from 21 TCGA
      cancer types, and created a comprehensive catalog of gene expression alterations
      for each cancer type. By clustering genes into co-regulated gene sets, we
      identified seven cross-cancer gene signatures altered across a diverse panel of
      primary human cancer samples. A 14-gene signature extracted from these seven
      cross-cancer gene signatures precisely differentiated between cancerous and
      normal samples, the predictive accuracy of leave-one-out cross-validation (LOOCV)
      were 92.04%, 96.23%, 91.76%, 90.05%, 88.17%, 94.29%, and 99.10% for BLCA, BRCA,
      COAD, HNSC, LIHC, LUAD, and LUSC, respectively. A lung cancer-specific gene
      signature, containing SFTPA1 and SFTPA2 genes, accurately distinguished lung
      cancer from other cancer samples, the predictive accuracy of LOOCV for TCGA and
      GSE5364 data were 95.68% and 100%, respectively. These gene signatures provide
      rich insights into the transcriptional programs that trigger tumorigenesis and
      metastasis, and many genes in the signature gene panels may be of significant
      value to the diagnosis and treatment of cancer. 

PMID- 26292931
TI  - Physical-Chemical Characterization and Formulation Considerations for Solid Lipid
      Nanoparticles.
AB  - Pure glyceryl mono-oleate (GMO) (lipid) and different batches of GMO commonly
      used for the preparation of GMO-chitosan nanoparticles were characterized by
      modulated differential scanning calorimetry (MDSC), cryo-microscopy, and cryo-X
      ray powder diffraction techniques. GMO-chitosan nanoparticles containing
      poloxamer 407 as a stabilizer in the absence and presence of polymers as
      crystallization inhibitors were prepared by ultrasonication. The effect of
      polymers (polyvinyl pyrrolidone (PVP), Eudragits, hydroxyl propyl methyl
      cellulose (HPMC), polyethylene glycol (PEG)), surfactants (poloxamer), and oils
      (mineral oil and olive oil) on the crystallization of GMO was investigated. GMO
      showed an exothermic peak at around -10 degrees C while cooling and another
      exothermic peak at around -12 degrees C while heating. It was followed by two
      endothermic peaks between 15 and 30 C, indicative of GMO melting. The results are
      corroborated by cryo-microscopy and cryo-X-ray. Significant differences in
      exothermic and endothermic transition were observed between different grades of
      GMO and pure GMO. GMO-chitosan nanoparticles resulted in a significant increase
      in particle size after lyophilization. MDSC confirmed that nanoparticles showed
      similar exothermic crystallization behavior of lipid GMO. MDSC experiments showed
      that PVP inhibits GMO crystallization and addition of PVP showed no significant
      increase in particle size of solid lipid nanoparticle (SLN) during
      lyophilization. The research highlights the importance of extensive physical
      chemical characterization for successful formulation of SLN. 

PMID- 26292932
TI  - [Histiocytic diseases in childhood and adolescence].
AB  - Histiocytic diseases are generally rare with a variable clinical course and
      variable morphology which often have a peak frequency of occurrence in childhood
      and adolescence. Histiocytoses are subdivided into Langerhans cell histiocytosis
      and the so-called non-Langerhans cell histiocytosis, such as juvenile
      xanthogranuloma, Erdheim-Chester disease and Rosai-Dorfman disease. The most
      common forms of histiocytosis in childhood are Langerhans cell histiocytosis and
      juvenile xanthogranuloma. In contrast, forms of histiocytosis which occur more
      frequently in adulthood, such as Erdheim-Chester disease and Rosai-Dorfman
      disease are rare in childhood. Some forms of histiocytosis harbor BRAFv600E
      mutations. In Langerhans cell histiocytosis they have been found in 50-55 % of
      the cases examined and in Erdheim-Chester disease in up to 100 % of cases. In the
      remaining forms of histiocytosis (especially juvenile xanthogranuloma and Rosai
      Dorfman disease) BRAF mutations could not be detected. A prognostic relevance
      could not be shown so far; however, in individual cases a mutation analysis of
      BRAF could provide help in the differential diagnostic considerations or the
      option of a therapy approach with BRAF inhibitors.

PMID- 26292933
TI  - [Differential diagnostic specific skin infiltrates in chronic myelomonocytic
      leukemia].
AB  - A 72-year-old male patient presented with multiple erythematous plaques on the
      lower arms, lower legs and feet. The patient suffered from rheumatoid arthritis
      and accompanying interstitial granulomatous dermatitis under treatment with
      tocilizumab. Several months prior to presentation a chronic myelomonocytic
      leukemia (CMML) had been diagnosed. The skin biopsy showed a perivascular
      infiltration of medium-sized cells with positivity for CD123, CD303 and CD4 with
      a low proliferation activity so that a diagnosis of a CMML-associated
      proliferation of plasmacytoid dendritic cells was made. The differential
      diagnosis of specific cutaneous infiltrates in CMML is discussed. 

PMID- 26292934
TI  - Liquid/liquid interface layering of 1-butanol and [bmim]PF6 ionic liquid: a
      nonlinear vibrational spectroscopy and molecular dynamics simulation study.
AB  - IR-visible sum-frequency generation (IV-SFG) vibrational spectroscopy and a
      molecular dynamics (MD) simulation were used to study the local layering order at
      the interface of 1-butanol-d9 and 1-butyl-3-methylimidazolium hexafluorophosphate
      ([bmim]PF6), a room-temperature ionic liquid (RTIL). The presence of a local non
      polar layer at the interface of the two polar liquids was successfully
      demonstrated. In the SFG spectra of 1-butanol-d9, we observed significant
      reduction and enhancement in the strength of the CD3 symmetric stretching (r(+))
      mode and the antisymmetric stretching (r(-)) mode peaks, respectively. The
      results can be well explained by the presence of an oppositely oriented quasi
      bilayer structure of butanol molecules, where the bottom layer is strongly bound
      by hydrogen-bonding with the PF6(-) anion. MD simulations reveal that the
      hydrogen-bonding of butanol with the PF6(-) anion causes the preferential
      orientation of the butanols; the restriction on the rotational distribution of
      the terminal methyl group along their C3 axis enhances the r(-) mode. As for the
      [bmim](+) cations, the SFG spectra taken within the CH stretch region indicate
      that the butyl chain of [bmim](+) points away from the bulk RTIL phase to the
      butanol phase at the interface. Combining the SFG spectroscopy and MD simulation
      results, we propose an interfacial model structure of layering, in which the
      butyl chains of the butanol molecules form a non-polar interfacial layer with the
      butyl chains of the [bmim](+) cations at the interface. 

PMID- 26292935
TI  - Epidemiology and emm types of invasive group A streptococcal infections in
      Finland, 2008-2013.
AB  - Invasive Streptococcus pyogenes (group A streptococcus, GAS) infections are a
      major global cause of morbidity and mortality. We analysed the surveillance data
      on invasive GAS and the microbiological characteristics of corresponding isolates
      to assess the incidence and emm type distribution of invasive GAS infections in
      Finland. Cases defined as patients with isolations of blood and cerebrospinal
      fluid S. pyogenes are mandatorily notified to the National Infectious Disease
      Registry and sent to the national reference laboratory for emm typing.
      Antimicrobial data were collected through the network including all clinical
      microbiology laboratories. Pulsed-field gel electrophoresis (PFGE) analysis was
      performed to assess clonality. In total, 1165 cases of invasive GAS were reported
      in Finland during 2008-2013; the median age was 52 years (range, 0-100) and 54%
      were male. The overall day 7 case fatality rate was 5.1% (59 cases). The average
      annual incidence was 3.6 cases per 100,000 population. A total of 1122 invasive
      GAS isolates (96%) were analysed by emm typing; 72 different emm types were
      identified, of which emm28 (297 isolates, 26%), emm89 (193 isolates, 12%) and
      emm1 (132 isolates, 12%) were the most common types. During 2008-2013, an
      increase of erythromycin resistance (1.9% to 8.7%) and clindamycin (0.9% to 9.2%)
      was observed. This resistance increase was in parallel with the introduction of a
      novel clone emm33 into Finland. The overall incidence of invasive GAS infections
      remained stable over the study period in Finland. We identified clonal spread of
      macrolide-resistant invasive emm33 GAS type, highlighting the importance of
      molecular surveillance.

PMID- 26292936
TI  - Low serum hyaluronic acid levels associated with spontaneous HBsAg clearance.
AB  - PURPOSE: The pathophysiological underlying mechanism of spontaneous HBsAg
      clearance in hepatitis B virus (HBV) infected patients is largely unknown.
      However, serum hyaluronic acid (sHA) plays a role in liver fibrosis progression
      and reversely could serve as a potential biomarker for HBsAg clearance. This
      study investigates whether low sHA is associated with HBsAg loss in non-Asian HBV
      patients. METHODS: Non-Asian women living in Amsterdam with known chronic HBV
      infection between 1990-2003 were invited for a single follow-up visit at the
      Municipal Health Service Amsterdam between September 2011 to May 2012. Serum
      hyaluronic acid and liver stiffness measurement together with clinical
      evaluation, biochemical and virologic blood tests were performed. RESULTS: Of the
      160 women, HBsAg loss occurred in 38 (23 %) patients between diagnosis and follow
      up. sHA levels were lower in HBsAg negative patients compared to HBsAg positive
      patients (14.5 [9.4-27.2] ng/mL vs 25.0 [12.3-42.5] ng/mL, p <0.01). A similar
      distinction in sHA between low and high HBV DNA was noted. sHA had a significant
      discriminatory ability to differentiate between HBsAg positive and HBsAg negative
      patients, (AUC 0.65 [95 % CI 0.55-0.75], p < 0.01). In multivariable analysis
      only sHA level was associated with HBsAg loss (OR 0.4 [0.2-0.9]). Finally, F3-F4
      fibrosis (cut-off >8.1 kPa) was diagnosed in 3 % in HBsAg negative patients
      compared to 10 % in HBsAg positive patients (p = 0.15). CONCLUSION: Serum HA
      levels are lower in patients who experience spontaneous HBsAg loss compared to
      HBsAg positive patients.

PMID- 26292937
TI  - Erratum to: Species distribution and in vitro antifungal susceptibility profiles
      of yeast isolates from invasive infections during a Portuguese multicenter
      survey.

PMID- 26292939
TI  - Effects of various fibre-rich extracts on cholesterol binding capacity during in
      vitro digestion of pork patties.
AB  - Intake of foods containing high levels of cholesterol harms human health, and an
      increase in the intake of dietary fibre (DF) may mitigate these negative effects.
      The co-products obtained from fruit juice extraction (lemon, grapefruit and
      pomegranate), lemon ice-cream production and tiger nut "horchata" (beverage) have
      been used for the production of fibre-rich extracts used as dietary fibre
      sources. The purpose of this study was to examine the effect of these fibre
      source additions on cholesterol retention during the in vitro digestion of pork
      patties. The control patties were prepared without fibre addition and for the
      rest of patties a 10% of each DF was added. The pork patties were then passed
      through an in vitro digestion model that simulated the composition of the mouth,
      stomach and small intestine juices. After digestion and centrifugation the
      product separated into 3 phases (oily, aqueous and pellet phase). The effect of
      each DF on the phase distribution and the amount of cholesterol retained in each
      phase were evaluated. All DFs studied showed an increase in the cholesterol
      retained in the pellet phase. The pomegranate DF showed a better result (32%
      cholesterol retained in the pellet phase). The application of these fibre-rich
      extracts in food elaboration processes due to their healthy properties could be
      very interesting if one of the most important properties that can be highlighted
      is their ability to adsorb cholesterol. 

PMID- 26292940
TI  - US drug agency approves drug for low sexual desire in women.

PMID- 26292938
TI  - Rheostatic Regulation of the SERCA/Phospholamban Membrane Protein Complex Using
      Non-Coding RNA and Single-Stranded DNA oligonucleotides.
AB  - The membrane protein complex between sarco(endo)plasmic reticulum Ca(2+)-ATPase
      (SERCA) and phospholamban (PLN) is a prime therapeutic target for reversing
      cardiac contractile dysfunctions caused by calcium mishandling. So far, however,
      efforts to develop drugs specific for this protein complex have failed. Here, we
      show that non-coding RNAs and single-stranded DNAs (ssDNAs) interact with and
      regulate the function of the SERCA/PLN complex in a tunable manner. Both in HEK
      cells expressing the SERCA/PLN complex, as well as in cardiac sarcoplasmic
      reticulum preparations, these short oligonucleotides bind and reverse PLN's
      inhibitory effects on SERCA, increasing the ATPase's apparent Ca(2+) affinity.
      Solid-state NMR experiments revealed that ssDNA interacts with PLN specifically,
      shifting the conformational equilibrium of the SERCA/PLN complex from an
      inhibitory to a non-inhibitory state. Importantly, we achieved rheostatic control
      of SERCA function by modulating the length of ssDNAs. Since restoration of Ca(2+)
      flux to physiological levels represents a viable therapeutic avenue for
      cardiomyopathies, our results suggest that oligonucleotide-based drugs could be
      used to fine-tune SERCA function to counterbalance the extent of the pathological
      insults. 

PMID- 26292941
TI  - Heterogeneous lineage marker expression in naive embryonic stem cells is mostly
      due to spontaneous differentiation.
AB  - Populations of cultured mouse embryonic stem cells (ESCs) exhibit a subfraction
      of cells expressing uncharacteristically low levels of pluripotency markers such
      as Nanog. Yet, the extent to which individual Nanog-negative cells are
      differentiated, both from ESCs and from each other, remains unclear. Here, we
      show the transcriptome of Nanog-negative cells exhibits expression of classes of
      genes associated with differentiation that are not yet active in cells exposed to
      differentiation conditions for one day. Long non-coding RNAs, however, exhibit
      more changes in expression in the one-day-differentiated cells than in Nanog
      negative cells. These results are consistent with the concept that Nanog-negative
      cells may contain subpopulations of both lineage-primed and differentiated cells.
      Single cell analysis showed that Nanog-negative cells display substantial and
      coherent heterogeneity in lineage marker expression in progressively nested
      subsets of cells exhibiting low levels of Nanog, then low levels of Oct4, and
      then a set of lineage markers, which express intensely in a small subset of these
      more differentiated cells. Our results suggest that the observed enrichment of
      lineage-specific marker gene expression in Nanog-negative cells is associated
      with spontaneous differentiation of a subset of these cells rather than the more
      random expression that may be associated with reversible lineage priming. 

PMID- 26292942
TI  - Compassionate use of orphan drugs.
AB  - BACKGROUND: EU regulation 726/2004 authorises manufacturers to provide drugs to
      patients on a temporary basis when marketing authorisation sought centrally for
      the entire EU is still pending. Individual Member States retain the right to
      approve and implement such 'compassionate use' programmes which companies will
      usually provide for free. Nevertheless some companies have opted not to partake
      in such programmes, in effect restricting access to drugs for patients in need.
      Here we survey the state of compassionate use programmes in the EU with
      particular reference to the rare disease field, and provide legal and ethical
      arguments to encourage their increased compassionate use in the EU and beyond. We
      contend that if enacted, these recommendations will be mutually beneficial to
      companies as well as patients. METHODS: Requests for information from the
      European Medicines Agency were made under the UK Freedom of Information Act 2000.
      Legal, ethical and economic/pragmatic analysis identified means by which
      provision of therapy in compassionate use programmes might be increased. RESULTS:
      More than 50 notifications of compassionate use programmes have been submitted to
      the EMA by Member States since 2006. About 40 % relate to orphan drugs. As there
      is a compulsory register of programmes but not of outcomes, their success is
      difficult to evaluate but, for example, the French programme expedited treatment
      for more than 20,000 (orphan and non-orphan) patients over a period of three
      years. CONCLUSION: Compelling self-interested, legal and ethical arguments can be
      mounted to encourage manufacturers to offer therapies on a compassionate use
      basis and these are often equally applicable to provision on a humanitarian aid
      basis. The EU's compassionate use programmes are instrumental in ensuring
      continuity of access to drugs until approval and reimbursement decisions are
      finalised. We propose the creation of a registry of drugs offered on a
      compassionate use basis; further transparency would allow such programmes to be
      evaluated and direct patients to sources of treatment.

PMID- 26292943
TI  - Stereospecific Coupling of Boronic Esters with N-Heteroaromatic Compounds.
AB  - A protocol for the stereospecific coupling of chiral secondary and tertiary
      boronic esters with lithiated N-heteroaromatics is described. The process
      involves initial boronate complex formation followed by addition of Troc-Cl,
      which activates the nitrogen and induces 1,2-migration. Oxidative workup
      furnishes the coupled product with >98% es. 

PMID- 26292944
TI  - Production and characterisation of Epstein-Barr virus helicase-primase complex
      and its accessory protein BBLF2/3.
AB  - The helicase-primase complex is part of the lytic DNA replication machinery of
      herpesviruses, but up to now, almost nothing is known about its structure. For
      Epstein-Barr virus it consists in the helicase BBLF4, the primase BSLF1 and the
      accessory protein BBLF2/3. The accessory protein shows only weak sequence
      homology within the herpesvirus family but may be related to an inactive B-family
      polymerase. BSLF1 belongs to the archaeo-eukaryotic primase family, whereas the
      helicase BBLF4 has been related either to Dda helicases of caudovirales or to
      Pif1 helicases. We produced the helicase-primase complex in insect cells using a
      baculovirus coding for all three proteins simultaneously. The soluble monomeric
      helicase-primase complex containing the three proteins with 1:1:1 stoichiometry
      showed ATPase activity, which is strongly stimulated in the presence of ssDNA
      oligomers. Furthermore, we expressed BBLF2/3 as soluble monomeric protein and
      performed small-angle X-ray scattering experiments which yielded an envelope
      whose shape is compatible with B-family polymerases.

PMID- 26292946
TI  - Too Much Medicine: Time to Stop Indiscriminate Cancer Screening.

PMID- 26292945
TI  - Putative phage-display epitopes of the porcine epidemic diarrhea virus S1 protein
      and their anti-viral activity.
AB  - Porcine epidemic diarrhea virus (PEDV) is a pathogen of swine that causes severe
      diarrhea and dehydration resulting in substantial morbidity and mortality in
      newborn piglets. Phage display is a technique with wide application, in
      particular, the identification of key antigen epitopes for the development of
      therapeutic and diagnostic reagents and vaccines. To identify antigen epitopes
      with specificity for PEDV, a monoclonal antibody (MAb-5E12) against the
      immunodominant region of the PEDV Spike protein (S1) was used as the target for
      biopanning a 12-mer phage display, random peptide library. After multiple rounds
      of biopanning and stringent washing, three phage-displayed peptides, designated
      L, W and H, were identified that recognize MAb-5E12. Sequence analysis showed
      that the one or more of the peptides exhibited partial sequence similarity to the
      native S1 sequence 'MQYVYTPTYYML' (designated peptide M) at position 201-212. In
      combination with software analysis for the prediction of B cell epitopes, aa 201
      212 exhibited characteristics of a linear epitope on the PEDV S1 protein. In
      contrast to peptide M, a consensus motif 'PxxY' was identified on both peptides L
      and W, and on the S1 protein, but not on peptide H. Peptide M and the MAb-5E12
      recognizing peptides L and W significantly inhibited the adsorption of PEDV on
      the cell surface as monitored through plaque-reduction assays. Furthermore, data
      from real-time PCR and indirect immunofluorescence assays were consistent with
      the ability of peptides M, L and W to block viral protein expression and thereby
      function as antiviral agents for PEDV. 

PMID- 26292947
TI  - Unipolar versus Bipolar Hemiarthroplasty for Displaced Femoral Neck Fractures in
      the Elderly: Is There a Difference?
AB  - INTRODUCTION: Hip hemiarthoplasties are commonly performed for displaced femoral
      neck fractures. Considerable differences of opinion exists regarding the choice
      between unipolar and bipolar designs. The main theoretical advantage of a bipolar
      over a unipolar prosthesis is the reduction of acetabular erosion due to movement
      taking place within the implant rather than at the acetabular implant interface.
      It is thus hypothesised that bipolar prostheses lead to better long-term
      functional outcomes with less complications. In this study, we aimed to compare
      unipolar (Moore's) and bipolar hemiarthroplasty looking specifically for
      differences in 1) pain and functional hip scores; 2) rates of acetabular erosion,
      component migration and revision surgery; and 3) rates of postoperative
      morbidity. MATERIALS AND METHODS: Inclusion criteria were 1) age more than or
      equal to 65 years; 2) displaced femoral neck fracture of non-pathologic origin;
      3) normal cognitive function; 4) ambulatory with or without assistive devices
      prior to the fracture; and 5) treated with a primary prosthetic replacement. Of
      the 193 patients that were available for review, 118 were in the Moore's group
      and 75 in the bipolar group. Postoperatively, patients were assessed with regards
      to pain, satisfaction, Modified Harris hip score and Oxford hip score. Standard
      anteroposterior pelvis and lateral hip radiographs were obtained at regular
      intervals. These were analysed specifically with regards to acetabular erosion
      and component migration. RESULTS: There was no significant difference between a
      Moore's and a bipolar prosthesis regarding hip pain, functional hip scores, rates
      of acetabular erosion, component migration, revision surgery and complications
      rates. CONCLUSION: Use of the more expensive bipolar prosthesis in elderly and
      premorbidly ambulant patient is not justified.

PMID- 26292948
TI  - Fasting during Ramadan and Associated Changes in Glycaemia, Caloric Intake and
      Body Composition with Gender Differences in Singapore.
AB  - INTRODUCTION: Millions of Muslim patients with diabetes mellitus (DM) fast during
      Ramadan. However, little is known about the metabolic impact of Ramadan fasting.
      We aimed to study the changes in body composition and metabolic profile in this
      group of patients. MATERIALS AND METHODS: We studied 29 Southeast Asian Muslim
      patients with type 2 diabetes; all underwent pre-Ramadan education. Study
      variables were weight change, body composition (using multifrequency bioimpedance
      method, InBody S20(r), Biospace, South Korea), blood pressure (BP), glycated
      haemoglobin (HbA1c), fasting lipid profile, and caloric intake assessment using
      FoodWorks(r) nutrient analysis software. RESULTS: Twenty-three subjects fasted
      >=15 days; mean +/- SD: 57 +/- 11 years; 52% were males. HbA1c improved
      significantly (8.6 +/- 2.4% pre-Ramadan vs 8.0 +/- 2.3% end-Ramadan, P = 0.017).
      Despite similar body weight, there was reduction in body fat mass (BFM) (30.9 +/-
      11 kg vs 29.2 +/- 12.2 kg, P = 0.013). Multivariate analysis suggested that the
      reduction in HbA1c was attributed by reduction in BFM (beta = -0.196, P = 0.034).
      There was no change in visceral adiposity (visceral fat area (VFA)) but
      stratification by gender showed a reduction amongst females (137.6 +/- 24.5 cm2
      to 132.5 +/- 25.7 cm2, P = 0.017). These changes occurred despite similar total
      caloric intake (1473.9 +/- 565.4 kcal vs 1473.1 +/- 460.4 kcal, P = 0.995), and
      proportion of carbohydrate (55.4 +/- 6.3% vs 53.3 +/- 7.5%, P = 0.25) and protein
      intake (17.6 +/- 4.1% vs 17.3 +/- 5.4%, P = 0.792), before and during Ramadan
      respectively, but with increased proportion of fat intake (11.9 +/- 2.4% vs 13 +/
      11.7%, P = 0.04). Seven out of 23 patients had medications adjusted to avert
      symptomatic hypoglycaemia but none of the patients developed severe
      hypoglycaemia. CONCLUSION: Ramadan fasting can be practiced safely with prior
      patient education and medication adjustment. It also confers modest benefits on
      metabolic profile and body composition, especially among females.

PMID- 26292949
TI  - How do English-speaking Cancer Patients Conceptualise Personhood?
AB  - INTRODUCTION: Understanding personhood or "what makes you, you" is pivotal to the
      provision of person-centred care. Yet the manner that personhood is conceived
      amongst patients varies significantly. This study aims to investigate conceptions
      of personhood in a multiracial, multicultural, multireligious setting. MATERIALS
      AND METHODS: A mixed-methods study was conducted at National Cancer Centre
      Singapore, from January 2013 to April 2013. We used a validated questionnaire
      where English-speaking oncology patients rated the importance of 26 features of
      "personhood" on a 10-point Likert scale from 0 to 9, with 9-points being
      extremely important. This was followed by a semi-structured interview. Analysis
      of transcripts using the Grounded Theory revealed original data that inspired
      novel ideas about the nature of personhood, which precipitated a further study in
      April 2014. RESULTS: Our initial study of 100 patients revealed that personhood
      is conceived in a unique and novel manner. To study this, we interviewed a
      further 40 patients using a supplemental question to our original questionnaire.
      Our data affirmed our initial findings and evidenced a change in conceptions of
      personhood. CONCLUSION: Our evidence supports the Ring Theory of Personhood,
      which suggests that personhood is defined by innate, individual, relational,
      societal elements. It also evidences that personhood is temporally and
      contextually sensitive allowing for better appreciation of the evolving goals of
      care that frequently occur at end-of- life. Most importantly, this study reminds
      healthcare professionals on the importance of "treating persons" and looking
      beyond familial interests in maintaining the interests and dignity of the
      patient.

PMID- 26292950
TI  - Epidemiology and Clinical Evolution of Liver Cirrhosis in Singapore.
AB  - INTRODUCTION: Liver cirrhosis is a common cause of morbidity and mortality and an
      important burden on the healthcare system. There is limited literature on liver
      cirrhosis in Singapore. We aimed to describe the epidemiology and clinical
      characteristics of cirrhotic patients seen in an ambulatory setting in a tertiary
      referral centre. MATERIALS AND METHODS: This is a retrospective observational
      cohort study of cirrhotic patients attending the ambulatory clinic of Singapore's
      largest tertiary hospital over 5 years. Cirrhosis was diagnosed on characteristic
      radiological features and/or histology. Aetiology of cirrhosis was determined by
      history, serology, biochemistry and/or histology. Data on decompensation events
      and death were retrieved from computerised hospital records. RESULTS: The study
      included 564 patients with median follow-up of 85 months. Mean age was 60.9 +/-
      12.5 years with 63.8% males. Main aetiologies of cirrhosis were chronic hepatitis
      B (CHB) (63.3%), alcohol (11.2%), cryptogenic (9%) and chronic hepatitis C (CHC)
      (6.9%). CHB was the predominant aetiology in Chinese and Malays whereas alcohol
      was the main aetiology in Indians. CHC cirrhosis was more common in Malays than
      other races. Majority had compensated cirrhosis with 76.8%/18.3%/5%; Child-Pugh
      A/B/C respectively. Decompensation events occurred in 155 patients (27.5%) and
      106 of them (18.8%) died. Diagnosis of cirrhosis via surveillance ultrasound was
      associated with improved 10-year survival. Age at diagnosis, portal vein
      thrombosis, Child-Pugh class and decompensation within 1 year of diagnosis were
      independent predictors of mortality. CONCLUSION: CHB is the primary cause of
      liver cirrhosis in Singapore. The major aetiologies of cirrhosis vary amongst the
      different ethnic groups. Cirrhotics with advanced age, portal vein thrombosis,
      poorer liver function and early decompensation have a higher mortality risk.

PMID- 26292951
TI  - Five Patients with Medullary Thyroid Carcinoma Presenting as Asymptomatic
      Elevation of Carcinoembryonic Antigen Level.

PMID- 26292952
TI  - An Alternative Diagnosis: Bartonella Neuroretinitis.

PMID- 26292953
TI  - Re: An Alternative Diagnosis: Bartonella Neuroretinitis.

PMID- 26292954
TI  - Associate Professor Dr Vijayan Appasamy (1953 - 2015).

PMID- 26292955
TI  - Measurement of early changes in anterior chamber morphology after cataract
      extraction measured by anterior segment optical coherence tomography.
AB  - OBJECTIVE: To evaluate the serial changes in anterior chamber depth (ACD) and
      angle parameters early after cataract surgery using anterior segment optical
      coherence tomography (ASOCT). METHODS: This was a retrospective chart review,
      case-control study; 150 eyes of 106 patients who underwent cataract surgery.
      Based on ACD and angle findings, the eyes were classified into two groups, open
      angle eyes (87 eyes) and narrow-angle eyes (63 eyes). ASOCT was used to measure
      ACD and angle parameters (angle opening distance, angle recess area, trabecular
      iris space area, and trabecular iris angle (TIA [1]). Serial changes in each
      group were measured before and 1 day, 1 week, and 1 month after cataract surgery,
      and the differences between the two groups were compared. RESULTS: ACD and all
      angle parameters in both groups at each examination time after cataract surgery
      were significantly different from the preoperative values (p < 0.01). In
      addition, all angle parameters significantly differed between the two groups at
      each examination time after cataract surgery (p < 0.001). However, ACD after
      surgery was not significantly different, irrespective of ACD before surgery. ACD
      and TIA500 both showed significantly greater changes from before surgery to 1 day
      after surgery in narrow-angle eyes compared to open-angle eyes (p < 0.001).
      CONCLUSIONS: Cataract surgery increases ACD and all angle parameters early after
      the surgery. However, the degree of angle widening in narrow-angle eyes was not
      as much as that in open-angle eyes, suggesting that factors other than the lens
      influence the angle closure.

PMID- 26292956
TI  - Organoboron-Promoted Regioselective Glycosylations in the Synthesis of a Saponin
      Derived Pentasaccharide from Spergularia ramosa.
AB  - Organoboron-mediated regioselective glycosylations were employed as key steps in
      the total synthesis of a branched pentasaccharide from a saponin natural product.
      The ability to use organoboron activation to differentiate OH groups in an
      unprotected glycosyl acceptor, followed by substrate-controlled reactions of the
      obtained disaccharide, enabled a streamlining of the synthesis relative to a
      protective group-based approach. This study revealed a matching/mismatching
      effect of the relative configuration of donor and acceptor on the efficiency of a
      regioselective glycosylation reaction, a problem that was solved through the
      development of a novel boronic acid-amine copromoter system for glycosyl acceptor
      activation. 

PMID- 26292957
TI  - Serum markers of CYFRA 21-1 and C-reactive proteins in oral squamous cell
      carcinoma.
AB  - BACKGROUND: CYFRA 21-1 (cytokeratin 19 fragment) and C-reactive proteins (CRP)
      were separately reported to be associated with prognosis of head and neck
      squamous cell carcinoma. The combined roles of CYFRA 21-1 and CRP levels were
      rarely investigated in oral squamous cell carcinoma (OSCC). The purpose of the
      present study was to analyze the relationship between preoperative levels of both
      CYFRA 21-1 and CRP, with clinicopathological factors and prognosis in OSCC
      patients. METHODS: A retrospective study was performed on 130 OSCC patients
      between December 2010 and June 2013. Their serum CYFRA 21-1 and CRP levels were
      measured preoperatively. RESULTS: CYFRA 21-1 level of >=3.3 ng/mL and CRP level
      of >=5.0 mg/L were significantly associated with pathological tumor status
      (P<0.001), tumor depth (>10 vs. <=10 mm, P=0.001), bone invasion (P=0.001), skin
      invasion (P=0.006), pathologic nodal metastasis (P=0.012), and disease-free
      survival (P=0.009). Higher CYPFRA 21-1 and CRP levels were also associated with
      higher risks of distant metastasis (log-rank test, P=0.013, (HR [95% CI]) 1.692
      [1.097-2.414]). CONCLUSIONS: Preoperative CYFRA 21-1 and CRP levels are probable
      candidates as biomarkers for risk stratification in OSCC.

PMID- 26292958
TI  - Clinical symptoms of lumbar spinal stenosis associated with morphological
      parameters on magnetic resonance images.
AB  - PURPOSE: This study aimed to investigate the association between the clinical
      symptoms of central lumbar spinal stenosis (CLSS) and morphological parameters
      using magnetic resonance imaging (MRI) data. METHODS: We retrospectively reviewed
      117 patients who visited our pain clinic from 2009 to 2013 and were diagnosed as
      CLSS. All patients underwent MRI of the L-spine and we measured the dural sac
      cross-sectional area (DSA), spinal canal cross-sectional area (SCA), ligamentum
      flavum cross-sectional area (LFA) and ligamentum flavum thickness (LFT) at the
      most stenotic intervertebral level on MRI. Clinical outcomes were investigated
      using the patient-assessed quantitative measurement of visual analog scale (VAS)
      and subjective disability was assessed by the Oswestry Disability Index (ODI).
      Additionally, subjective walking distance (SWD) was also collected from
      electronic medical records. RESULTS: There were no statistically significant
      correlations found between the VAS score and the DSA, SCA, LFA, and LFT. A
      statistically significant linear association existed between the DSA and SCA and
      the subjective walking distance (r=0.201, P=0.045 and r=0.198, P=0.049,
      respectively) indicating that the larger the DSA or SCA, the longer the SWD
      before the occurrence of claudication. The LFA and LFT were significantly
      correlated with the ODI score (r=0.249, P=0.007 and r=0.250, P=0.007,
      respectively). CONCLUSION: Larger LFA and LFT values are associated with higher
      ODI values. A larger DSA and SCA are associated with a longer SWD before
      claudication occurs. To evaluate CLSS patients, clinicians should more carefully
      inspect the integral morphological parameters than the individual morphological
      parameters.

PMID- 26292959
TI  - Effect of pre-procedural interrupted apixaban on heparin anticoagulation during
      catheter ablation for atrial fibrillation: a prospective observational study.
AB  - PURPOSE: Effective intraprocedural anticoagulation is considered essential to
      minimize the risk of thromboembolism in catheter ablation (CA) of atrial
      fibrillation (AF). The effect of interrupted apixaban on intraprocedural heparin
      dosing requirements and levels of achieved anticoagulation with heparin has not
      been well studied. The purpose of the present study was to compare heparin
      administration and activated clotted times (ACTs) for patients undergoing CA for
      AF treated with interrupted apixaban before the procedure with patients on
      uninterrupted warfarin. METHODS: Consecutive patients undergoing CA for AF
      treated with interrupted apixaban or uninterrupted warfarin were prospectively
      enrolled. Heparin administration determined by a standard protocol and normalized
      to patient weight and procedure duration, as well as rapidity, and degree of
      anticoagulation with heparin (as measured by mean ACT, peak ACT, time to ACT
      >=300 s, and time to ACT >=350 s) were compared between the groups. RESULTS:
      Forty-eight patients were enrolled (25 apixaban and 23 warfarin). Heparin
      administered by bolus (51.3 +/- 21.5 vs 27.8 +/- 9.6 units/kg/h; p < 0.001) and
      mean heparin drip rate (25.3 +/- 3.6 vs 20.7 +/- 2.4 units/kg/h; p < 0.001) were
      significantly higher in the apixaban group compared to the warfarin group.
      Despite greater heparin administration, apixaban patients achieved a
      significantly lower mean ACT (332.3 +/- 17.0 vs 384.5 +/- 53.9; p < 0.001) and
      peak ACT (369.5 +/- 22.6 vs 432.3 +/- 75.8, p < 0.001) compared to the warfarin
      group. The time to ACT >=350 s (66.7 +/- 35.8 vs 26.9 +/- 34.0; p < 0.001) was
      significantly longer for apixaban-treated patients. Outcome differences persisted
      after analysis using linear models and Cox proportional hazard regression with
      adjustment for propensity scores. CONCLUSIONS: A standard intraprocedural heparin
      protocol results in delayed and lower levels of anticoagulation as measured by
      the ACT for interrupted apixaban-treated patients in comparison to those on
      uninterrupted warfarin during CA of AF.

PMID- 26292960
TI  - Cook and Chill: Effect of Temperature on the Performance of Nonequilibrated Blood
      Glucose Meters.
AB  - BACKGROUND: Exposure to extreme temperature can affect the performance of blood
      glucose monitoring systems. The aim was to determine the non-equilibrated
      performance of these systems at extreme high and low temperatures that can occur
      in daily life. METHODS: The performances of 5 test systems, (1) Abbott FreeStyle
      Freedom Lite, (2) Roche AccuChek Aviva, (3) Bayer Contour, (4) LifeScan OneTouch
      Verio, and (5) Sanofi BG Star, were compared after "cooking" (50 degrees C for 1
      hour) or "chilling" (-5 degrees C for 1 hour) with room temperature controls (23
      degrees C) using whole blood with glucose concentrations of 50, 100, and 200
      mg/dl. RESULTS: The equilibration period (time from the end of incubation to when
      the test system is operational) was between 1 and 8 minutes, and each test system
      took between 15 and 30 minutes after incubation to obtain stable measurements at
      room temperature. Incubating the strips at -5 degrees C or 50 degrees C had
      little effect on the glucose measurement, whereas incubating the meters
      introduced bias in performance between 0 and 15 minutes but not subsequently,
      compared to room temperature controls and at all 3 glucose levels. CONCLUSIONS:
      Compensating technologies embedded within blood glucose monitoring systems
      studied here perform well at extreme temperatures. People with diabetes need to
      be alerted to this feature to avoid perceptions of malperformance of their
      devices and the possible inability to get blood glucose readings on short notice
      (eg, during time of suspected rapid change or before an unplanned meal).

PMID- 26292961
TI  - Mixed Influence of Electronic Health Record Implementation on Diabetes Order
      Patterns for Michigan Medicaid Adults.
AB  - BACKGROUND: These 2011-2013 analyses examined the authors' hypothesis that
      relative diabetes care order changes would be measured after electronic health
      record (EHR) implementation for 291 Medicaid adults who received all of their
      office-based care at one midwestern federally qualified health center (FQHC) over
      a 24-month period (n = 2727 encounters, 2489 claims). METHOD: Beneficiary
      sociodemographic, clinical, and claims data were validated with clinic EHR and
      state Medicaid claims linked to providers' national identifier numbers. Overall
      pre-post order rate comparisons, and a series of controlled within group binary
      logistic models were conducted under penalized maximum likelihood estimation
      terms. RESULTS: After EHR implementation, both the overall order rates and odds
      ratios of per beneficiary hemoglobin A1C (HbA1C) orders increased significantly
      (ie, from mean of 0.65 [SD = 1.19] annual tests to 0.96 tests [SD = 1.24] [P <
      .001]). Although the overall post-EHR order rates of dilated eye exams and
      microalbumin urine tests appeared fairly stable, the odds of eye exam orders
      being placed at the claims level decreased significantly (OR = 0.774, P = .0030).
      CONCLUSIONS: These mixed results provide evidence of the varied diabetes care
      ordering patterns likely seen from increased office use of EHR technologies. The
      authors attempt to explain these post-EHR differences (or lack of) that generally
      resemble some of the authors' results from another funded project. Ideally, these
      findings provide Medicaid and health care officials with a more realistic
      indication of how EHRs may, or may not, influence diabetes care ordering patterns
      for vulnerable lower-income primary health care consumers.

PMID- 26292963
TI  - Plexin-D1/Semaphorin 3E pathway may contribute to dysregulation of vascular tone
      control and defective angiogenesis in systemic sclerosis.
AB  - INTRODUCTION: The vascular and nervous systems have several anatomic and
      molecular mechanism similarities. Emerging evidence suggests that proteins
      involved in transmitting axonal guidance cues, including members of class III
      semaphorin (Sema3) family, play a critical role in blood vessel guidance during
      physiological and pathological vascular development. Sema3E is a natural
      antiangiogenic molecule that causes filopodial retraction in endothelial cells,
      inhibiting cell adhesion by disrupting integrin-mediated adhesive structures. The
      aim of the present study was to investigate whether in systemic sclerosis (SSc)
      Plexin-D1/Sema3E axis could be involved in the dysregulation of vascular tone
      control and angiogenesis. METHODS: Sema3E levels were measured by quantitative
      colorimetric sandwich ELISA in serum samples from 48 SSc patients, 45 subjects
      with primary Raynaud's phenomenon (pRP) and 48 age-matched and sex-matched
      healthy controls. Immunofluorescence staining on skin sections from 14 SSc
      patients and 12 healthy subjects was performed to evaluate Sema3E and Plexin-D1
      expression. Western blotting was used to assess Plexin-D1/Sema3E axis in human
      SSc and healthy dermal microvascular endothelial cells (SSc-MVECs and H-MVECs,
      respectively) at basal condition and after stimulation with recombinant human
      vascular endothelial growth factor (VEGF), SSc and healthy sera. Capillary
      morphogenesis on Matrigel was performed on H-MVECs treated with healthy, pRP or
      SSc sera in the presence of Sema3E and Plexin-D1 soluble peptides. RESULTS: Serum
      Sema3E levels were significantly higher both in pRP subjects and SSc patients
      than in controls. In SSc, Sema3E levels were significantly increased in patients
      with early nailfold videocapillaroscopy (NVC) pattern compared to active/late
      patterns and pRP, and in patients without digital ulcers versus those with
      ulcers. In SSc skin, Sema3E expression was strongly increased in the
      microvascular endothelium. Cultured SSc-MVECs showed higher levels of
      phosphorylated Plexin-D1 and Sema3E expression than H-MVECs, and stimulation with
      SSc sera increased phosphorylated Plexin-D1 and Sema3E in H-MVECs. The addition
      of Sema3E-binding Plexin-D1 soluble peptide significantly attenuated the
      antiangiogenic effect of SSc sera on H-MVECs. CONCLUSIONS: Our findings suggest
      that Plexin-D1/Sema3E axis is triggered in SSc endothelium and may have a role in
      the dysregulation of angiogenesis and vascular tone control by inducing neuro
      vascular mechanism alterations clinically evident in particular in the early
      disease phases.

PMID- 26292964
TI  - Binocular function to increase visual outcome in patients implanted with a
      diffractive trifocal intraocular lens.
AB  - BACKGROUND: To evaluate binocular visual outcome for near, intermediate and
      distance compared to monocular visual outcome at the same distances in patients
      implanted with a diffractive trifocal intraocular lens (IOL). METHODS: The study
      comprised of 100 eyes of 50 patients that underwent bilateral refractive lens
      exchange or cataract surgery with implantation of a multifocal diffractive IOL
      (AT LISA tri 839MP, Carl Zeiss Meditech, Germany). A complete ophthalmological
      examination was performed preoperatively and 3 month postoperatively. The main
      outcome measures were monocular and binocular uncorrected distance (UDVA),
      corrected distance (CDVA), uncorrected intermediate (UIVA), and uncorrected near
      visual acuities (UNVA), keratometry, and manifest refraction. RESULTS: The mean
      age was 59.28 years +/- 9.6 [SD] (range 44-79 years), repectively. There was
      significant improvement in UDVA, UIVA, UNVA and CDVA. Comparing the monocular
      results to the binocular results there was a statistical significant better
      binocular outcome in all distances (UDVA p = 0.036; UIVA p < 0.0001; UNVA p =
      0.001). The postoperative manifest refraction was in 86 % of patients within +/-
      0.50 [D]. CONCLUSIONS: The trifocal IOL improved near, intermediate, and distance
      vision compared to preoperatively. In addition a statistical significant increase
      for binocular visual function in all distances could be found. TRIAL
      REGISTRATION: German Clinical Trials Register (DRKS) DRKS00007837.

PMID- 26292962
TI  - Cortical activity differs between position- and force-control knee extension
      tasks.
AB  - Neural control differs between position- and force-control tasks as evident from
      divergent effects of fatigue and pain. Unlike force-control tasks, position
      control tasks focus on a postural goal to maintain a joint angle. Cortical
      involvement is suggested to be less during postural control, but whether this
      differs between position- and force-control paradigms remains unclear. Coherence
      estimates the functional communication between spatially distinct active regions
      within the cortex (cortico-cortical coherence; CCC) and between the cortex and
      muscles (corticomuscular coherence; CMC). We investigated whether cortical
      involvement differed between force-control and more posturally focused, position
      control tasks. Seventeen adults performed position- and force-control knee
      extensor efforts at a submaximal load (10 % maximum voluntary contraction).
      Surface electromyography was recorded from the right knee extensor and flexor
      muscles and brain activity using electroencephalography (EEG). CCC and CMC in the
      beta (13-30 Hz) and gamma (30-45 Hz) frequency bands were calculated between
      combinations of intra- and inter-hemispheric pairs of electrodes, and between
      four EEG electrodes that approximated the left motor cortical area, and right
      knee extensor EMG, respectively. Differences in EEG power and muscle activity
      were also calculated. CCC was greater across distributed regions in the force
      control task. Beta EEG power in the left hemisphere was higher for the position
      control task. Although averaged CMC data differed between tasks, there was no
      task difference for individual CMC data. Muscle activity and force did not differ
      between tasks. The results demonstrate differential cortical contributions to
      control force- versus position-control tasks. This might contribute to
      differences in performance outcomes of these tasks that have been shown
      previously. 

PMID- 26292965
TI  - Simple synthesis of highly catalytic carbon-free MnCo2O4@Ni as an oxygen
      electrode for rechargeable Li-O2 batteries with long-term stability.
AB  - An effective integrated design with a free standing and carbon-free architecture
      of spinel MnCo2O4 oxide prepared using facile and cost effective hydrothermal
      method as the oxygen electrode for the Li-O2 battery, is introduced to avoid the
      parasitic reactions of carbon and binder with discharge products and reaction
      intermediates, respectively. The highly porous structure of the electrode allows
      the electrolyte and oxygen to diffuse effectively into the catalytically active
      sites and hence improve the cell performance. The amorphous Li2O2 will then
      precipitate and decompose on the surface of free-standing catalyst nanorods.
      Electrochemical examination demonstrates that the free-standing electrode without
      carbon support gives the highest specific capacity and the minimum capacity
      fading among the rechargeable Li-O2 batteries tested. The Li-O2 cell has
      demonstrated a cyclability of 119 cycles while maintaining a moderate specific
      capacity of 1000 mAh g(-1). Furthermore, the synergistic effect of the fast
      kinetics of electron transport provided by the free-standing structure and the
      high electro-catalytic activity of the spinel oxide enables excellent performance
      of the oxygen electrode for Li-O2 cells. 

PMID- 26292966
TI  - Factors affecting dural penetration and prognosis in patients admitted to
      emergency department with cranial gunshot wound.
AB  - PURPOSE: To explore the effect of admission physical examination findings,
      anamnesis, and computed tomography on dural penetration and prognosis in patients
      with cranial gunshot wound (CGW). METHODS: In this study, the medical data of 56
      subjects who were admitted to the Emergency Department of Dicle University
      Hospital with CGWs between January 2011 and December 2013 were retrospectively
      reviewed. The effects of type of incident (suicidal vs non-suicidal), pupil
      diameter and light reflex, hemodynamic status, type (bullet or pellet), velocity,
      trajectory of foreign material, trauma scores, and imaging findings on dural
      penetration and mortality were explored. RESULTS: The mean age of the study
      population was 24.8 +/- 13.50 years. Thirty (53.6 %) patients had penetrating
      injuries and 26 (46.4 %) had non-penetrating injuries; 9 (16.1 %) patients died
      and 47 (83.9 %) survived. Suicidal injury, pupil diameter and light reflex,
      bullet as foreign material, and high velocity and lateral trajectory of foreign
      material significantly affected dural penetration and mortality (p < 0.05). In
      addition, dural penetration, bilobar, multilobar, or bihemispheric involvement of
      brain parenchyma, presence of intracranial hemorrhage, subarachnoid hemorrhage,
      ventricular hemorrhage, fracture, shift, edema, and trauma scores significantly
      affected mortality (p < 0.05). CONCLUSIONS: In CGWs, dural penetration and
      prognosis can be predicted by physical examination findings and patient
      characteristics on initial admission.

PMID- 26292967
TI  - Ubiquitination switches EphA2 vesicular traffic from a continuous safeguard to a
      finite signalling mode.
AB  - Autocatalytic phosphorylation of receptor tyrosine kinases (RTKs) enables
      diverse, context-dependent responses to extracellular signals but comes at the
      price of autonomous, ligand-independent activation. Using a conformational
      biosensor that reports on the kinase activity of the cell guidance ephrin
      receptor type-A (EphA2) in living cells, we observe that autonomous EphA2
      activation is suppressed by vesicular recycling and dephosphorylation by protein
      tyrosine phosphatases 1B (PTP1B) near the pericentriolar recycling endosome. This
      spatial segregation of catalytically superior PTPs from RTKs at the plasma
      membrane is essential to preserve ligand responsiveness. Ligand-induced
      clustering, on the other hand, promotes phosphorylation of a c-Cbl docking site
      and ubiquitination of the receptor, thereby redirecting it to the late
      endosome/lysosome. We show that this switch from cyclic to unidirectional
      receptor trafficking converts a continuous suppressive safeguard mechanism into a
      transient ligand-responsive signalling mode. 

PMID- 26292968
TI  - miR-526b targets 3' UTR of MMP1 mRNA.
AB  - Regulation of matrix metalloproteinases (MMPs) is important for many
      physiological processes involving cancers, inflammation, tissue remodeling and
      skin aging. Here, we report the novel finding that the expression of MMP1 mRNA is
      downregulated by the overexpression of miR-526b which is a member of chromosome
      19 microRNA cluster (C19MC). Our analysis using reporter constructs containing
      the 3' untranslated region (3' UTR) of MMP1 and its mutant form showed that the
      region from 377-383 in the 3' UTR of MMP1 is critical for targeting by miR-526b.
      In addition, the expression pattern of miR-526b and MMP1 mRNA showed reverse
      relation between adult dermal and neonatal fibroblasts. We show for the first
      time that miR-526b, an miRNA belonging to C19MC, can target the 377-383 region of
      the MMP1 3' UTR. 

PMID- 26292971
TI  - Advanced Anticorrosion Coating Materials Derived from Sunflower Oil with
      Bifunctional Properties.
AB  - High-performance barrier films preventing permeation of moisture, aggressive
      chloride ions, and corrosive acids are important for many industries ranging from
      food to aviation. In the current study, pristine sunflower oil was used to form
      uniform adherent films on iron (Fe) via a simple single-step thermal treatment
      (without involving any initiator/mediator/catalyst). Oxidation of oil on heating
      results in a highly conjugated (oxidized) crystalline lamellar network with
      interlayer separation of 0.445 nm on Fe. The electrochemical corrosion tests
      proved that the coating exhibits superior anticorrosion performance with high
      coating resistance (>10(9) ohm cm2) and low capacitance values (<10(-10) F cm(
      2)) as compared to bare Fe, graphene, and conducting polymer based coatings in 1
      M hydrochloric acid solutions. The electrochemical analyses reveal that the oil
      coatings developed in this study provided a two-fold protection of passivation
      from the oxide layer and barrier from polymeric films. It is clearly observed
      that there is no change in structure, morphology, or electrochemical properties
      even after a prolonged exposure time of 80 days. This work indicates the prospect
      of developing highly inert, environmentally green, nontoxic, and micrometer level
      passivating barrier coatings from more sustainable and renewable sources, which
      can be of interest for numerous applications.

PMID- 26292969
TI  - Exploring the treatment delay in the care of patients with ST-elevation
      myocardial infarction undergoing acute percutaneous coronary intervention: a
      cross-sectional study.
AB  - BACKGROUND: A short delay between diagnosis and treatment for patients diagnosed
      with ST-elevation myocardial infarction (STEMI) is vital to prevent cardiac
      damage and mortality. The objective of this study was to explore the treatment
      delay and associated factors in the management of patients diagnosed with STEMI
      going for percutaneous coronary intervention (PCI). METHODS: In a cross-sectional
      multicenter study, the treatment delay (time between first electrocardiogram and
      start of PCI procedure) of STEMI patients in seven PCI centers in the Netherlands
      was measured. Data were analyzed by means of multivariable generalized linear
      models, accounting for a non-normally distributed outcome and clustering of
      patients within centers. RESULTS: In total, 1017 patient charts were included.
      The majority of the patients (78.7%) were treated within the guideline
      recommended time target of 90 min. Overall, the median treatment delay was 64 min
      (interquartile range 47-82). A significantly prolonged delay was found among
      patients of whom their first electrocardiogram was performed at a general
      practitioner's practice (+23.9 min; 95% confidence interval 9.9-40.8) or in
      hospital (+9.5 min; 95% confidence interval 2.5-17.3), patients requiring
      interhospital transfer (+14.6 min; 95% confidence interval 7.6-22.4) or
      presenting with acute heart failure on admission (+17.6 min; 95% confidence
      interval 7.9-28.7). CONCLUSIONS: Despite a short median delay between first
      electrocardiogram and PCI, the time targets are occasionally exceeded for
      patients diagnosed with STEMI. To further improve the process of care, PCI
      centers should focus on improving regional STEMI care networks, involving general
      practitioners, emergency departments and referring hospitals.

PMID- 26292973
TI  - SCN9A-associated congenital insensitivity to pain and anosmia in an Irish
      patient.

PMID- 26292972
TI  - Iron oxides in human spleen.
AB  - Iron is an essential element for fundamental cell functions and a catalyst for
      chemical reactions. Three samples extracted from the human spleen were
      investigated by scanning (SEM) and transmission electron microscopy (TEM),
      Mossbauer spectrometry (MS), and SQUID magnetometry. The sample with diagnosis of
      hemosiderosis (H) differs from that referring to hereditary spherocytosis and the
      reference sample. SEM reveals iron-rich micrometer-sized aggregate of various
      structures-tiny fibrils in hereditary spherocytosis sample and no fibrils in
      hemochromatosis. Hematite and magnetite particles from 2 to 6 MUm in TEM with
      diffraction in all samples were shown. The SQUID magnetometry shows different
      amount of diamagnetic, paramagnetic and ferrimagnetic structures in the tissues.
      The MS results indicate contribution of ferromagnetically split sextets for all
      investigated samples. Their occurrence indicates that at least part of the sample
      is magnetically ordered below the critical temperature. The iron accumulation
      process is different in hereditary spherocytosis and hemosiderosis. This fact may
      be the reason of different iron crystallization. 

PMID- 26292974
TI  - Models of Ion Solvation Thermodynamics in Ethylene Carbonate and Propylene
      Carbonate.
AB  - Ethylene carbonate (EC) and propylene carbonate (PC) are organic solvents used
      extensively in energy storage applications such as lithium-ion batteries and
      supercapacitors. Using statistical mechanical theory and computer simulations,
      this paper compares and contrasts the thermodynamics of ion solvation in EC and
      PC with the behavior observed in water. The EC and PC solvents are modeled with
      the AMBER (GAFF) force field. Ion-solvent interactions are treated with two point
      charge models: one using an existing Lennard-Jones ion parameter set optimized
      for solvation in water, and the other based on high-level quantum calculations on
      ion-solvent dimers and fitting to a Buckingham-type potential form. The second
      model produces a coordination number for the Li(+) ion in closer agreement with
      experiment. Neither model yields consistently accurate solvation thermodynamic
      quantities (free energies, enthalpies, and entropies), however. The simulations
      and thermodynamic analysis illustrate key physical aspects of the solvation; the
      studies also point to necessary modifications of these simple models. In
      particular, the calculations show that polarization and associated dispersion
      forces are important and that well-optimized polarizable or quantum models are
      likely required to accurately reproduce condensed-phase properties of ions in
      these technologically important solvents. 

PMID- 26292975
TI  - Covalent Triazine-Based Frameworks as Visible Light Photocatalysts for the
      Splitting of Water.
AB  - Covalent triazine-based frameworks (CTFs) with a graphene-like layered morphology
      have been controllably synthesized by the trifluoromethanesulfonic acid-catalyzed
      nitrile trimerization reactions at room temperature via selecting different
      monomers. Platinum nanoparticles are well dispersed in CTF-T1, which is ascribed
      to the synergistic effects of the coordination of triazine moieties and the
      nanoscale confinement effect of CTFs. CTF-T1 exhibits excellent photocatalytic
      activity and stability for H2 evolution in the presence of platinum under visible
      light irradiation (lambda >= 420 nm). The activity and stability of CTF-T1 are
      comparable to those of g-C3 N4 . Importantly, as a result of the tailorable
      electronic and spatial structures of CTFs that can be achieved through the
      judicial selection of monomers, CTFs not only show great potential as organic
      semiconductor for photocatalysis but also may provide a molecular-level
      understanding of the inherent heterogeneous photocatalysis. 

PMID- 26292976
TI  - Improvements in Interpersonal Functioning Following Interpersonal Psychotherapy
      (IPT) with Adolescents and their Association with Change in Depression.
AB  - BACKGROUND: This study adds to the body of evidence regarding the theoretical
      underpinnings of interpersonal psychotherapy and the mechanisms through which it
      impacts upon depression in adolescents. AIMS: The aims were to determine whether
      the interpersonal constructs proposed to underpin interpersonal psychotherapy do
      indeed change in response to this therapy and whether such changes are associated
      with changes in depression in young people. METHOD: Thirty-nine adolescents, aged
      13-19 years, with a primary diagnosis of major depressive disorder, were randomly
      assigned in blocks to group or individual treatment. Assessments were conducted
      at pre and posttreatment, and 12-month follow-up. RESULTS: The results supported
      the hypotheses, with significant improvements in social skills, social
      functioning, and the quality of parent-adolescent relationships, and an increase
      in secure attachment style and decrease in insecure attachment style being
      evident following treatment. Benefits were maintained at 12-month follow-up.
      Adolescents who showed greater reductions in depressive symptoms over this period
      tended to also show greater improvement in parent reported social skills, quality
      of the parent-adolescent relationship, and attachment style from pretreatment to
      12-month follow-up. CONCLUSIONS: The findings are consistent with the proposed
      underpinnings of interpersonal psychotherapy. Adolescents showed significant
      improvements in interpersonal functioning and changes in attachment style
      following treatment, and changes in social skills, parent-adolescent conflict and
      attachment style were associated with reductions in depression. As such, the
      results add to the body of knowledge regarding the construct validity of
      interpersonal psychotherapy as an intervention for depression in young people.
      Clinical implications and directions for future research are discussed.

PMID- 26292977
TI  - A role for 12/15-lipoxygenase-derived proresolving mediators in postoperative
      ileus: protectin DX-regulated neutrophil extravasation.
AB  - Resolution of inflammation is an active counter-regulatory mechanism involving
      polyunsaturated fatty acid-derived proresolving lipid mediators. Postoperative
      intestinal motility disturbances, clinically known as postoperative ileus, occur
      frequently after abdominal surgery and are mediated by a complex inflammation of
      the intestinal muscularis externa. Herein, we tested the hypothesis that
      proresolving lipid mediators are involved in the resolution of postoperative
      ileus. In a standardized experimental model of postoperative ileus, we detected
      strong expression of 12/15-lipoxygenase within the postoperative muscularis
      externa of C57BL/6 mice, predominately located within CX3CR1(+)/Ly6C(+)
      infiltrating monocytes rather than Ly6G(+) neutrophils. Mass spectrometry
      analyses demonstrated that a 12/15-lipoxygenase increase was accompanied by
      production of docosahexaenoic acid-derived lipid mediators, particularly
      protectin DX and resolvin D2, and their common precursor 17-hydroxy
      docosahexaenoic acid. Perioperative administration of protectin DX, but not
      resolvin D2 diminished blood-derived leukocyte infiltration into the surgically
      manipulated muscularis externa and improved the gastrointestinal motility. Flow
      cytometry analyses showed impaired Ly6G(+)/Ly6C(+) neutrophil extravasation after
      protectin DX treatment, whereas Ly6G(-)/Ly6C(+) monocyte numbers were not
      affected. 12/15-lipoxygenase-deficient mice, lacking endogenous protectin DX
      synthesis, demonstrated increased postoperative leukocyte levels. Preoperative
      intravenous administration of a docosahexaenoic acid-rich lipid emulsion reduced
      postoperative leukocyte infiltration in wild-type mice but failed in 12/15
      lipoxygenase-deficient mice mice. Protectin DX application reduced leukocyte
      influx and rescued 12/15-lipoxygenase-deficient mice mice from postoperative
      ileus. In conclusion, our results show that 12/15-lipoxygenase mediates
      postoperative ileus resolution via production of proresolving docosahexaenoic
      acid-derived protectin DX. Perioperative, parenteral protectin DX or
      docosahexaenoic acid supplementation, as well as modulation of the 12/15
      lipoxygenase pathway, may be instrumental in prevention of postoperative ileus. 

PMID- 26292980
TI  - The use of mobile technology in health libraries: a summary of a UK-based survey.
AB  - BACKGROUND: Health libraries have changed over the past fifteen years in the
      format of the information they provide. This is driven by developments in
      technology. OBJECTIVES: To conduct a survey of NHS health libraries in the United
      Kingdom in order to summarise how mobile technologies are being used, how they
      are promoted and how they are delivered, highlighting good practice and solutions
      to issues. METHODS: An online survey was carried out in 2013 and sent to academic
      and NHS web-based discussion lists. There were 199 responses. RESULTS: Main
      replies were from large Acute Hospital Trusts. Only 18% of respondents had
      conducted research into use of mobile technology (MT) within their Trust. Forty
      per cent of Trusts offered clinical point of care tools, 29% mobile catalogues,
      and 30% had mobile enabled web sites. Libraries utilised third-party partnerships
      rather than develop their own applications or tools. Seventy per cent of Trusts
      promoted new MT services via e-mail. Network restrictions were the main barrier
      to development as well as finance and expertise. CONCLUSIONS: Uptake and
      development of MT is sporadic and driven by individuals. There is an opportunity
      for collaboration and sharing resources and expertise. There are benefits to
      adopting user-friendly resources.

PMID- 26292979
TI  - Neutrophil contributions to the induction and regulation of the acute
      inflammatory response in teleost fish.
AB  - Neutrophils are essential to the acute inflammatory response, where they serve as
      the first line of defense against infiltrating pathogens. We report that, on
      receiving the necessary signals, teleost (Carassius auratus) neutrophils leave
      the hematopoietic kidney, enter into the circulation, and dominate the initial
      influx of cells into a site of inflammation. Unlike mammals, teleost neutrophils
      represent <5% of circulating leukocytes during periods of homeostasis. However,
      this increases to nearly 50% immediately after intraperitoneal challenge with
      zymosan, identifying a period of neutrophilia that precedes the peak influx of
      neutrophils into the challenge site at 18 h after injection). We demonstrate that
      neutrophils at the site of inflammation alter their phenotype throughout the
      acute inflammatory response, and contribute to both the induction and the
      resolution of inflammation. However, neutrophils isolated during the
      proinflammatory phase (18 h after injection) produced robust respiratory burst
      responses, released inflammation-associated leukotriene B(4), and induced
      macrophages to increase reactive oxygen species production. In contrast,
      neutrophils isolated at 48 h after infection (proresolving phase) displayed low
      levels of reactive oxygen species, released the proresolving lipid mediator
      lipoxin A(4), and downregulated reactive oxygen species production in macrophages
      before the initiation of apoptosis. Lipoxin A(4) was a significant contributor to
      the uptake of apoptotic cells by teleost macrophages and also played a role, at
      least in part, in the downregulation of macrophage reactive oxygen species
      production. Our results highlight the contributions of neutrophils to both the
      promotion and the regulation of teleost fish inflammation and provide added
      context for the evolution of this hematopoietic lineage.

PMID- 26292981
TI  - Heat tolerance in Drosophila subobscura along a latitudinal gradient: Contrasting
      patterns between plastic and genetic responses.
AB  - Susceptibility to global warming relies on how thermal tolerances respond to
      increasing temperatures through plasticity or evolution. Climatic adaptation can
      be assessed by examining the geographic variation in thermal-related traits. We
      studied latitudinal patterns in heat tolerance in Drosophila subobscura reared at
      two temperatures. We used four static stressful temperatures to estimate the
      thermal death time (TDT) curves, and two ramping assays with fast and slow
      heating rates. Thermal death time curves allow estimation of the critical thermal
      maximum (CT(max)), by extrapolating to the temperature that would knock down the
      flies almost "instantaneously," and the thermal sensitivity to increasing
      stressful temperatures. We found a positive latitudinal cline for CT(max), but no
      clinal pattern for knockdown temperatures estimated from the ramping assays.
      Although high-latitude populations were more tolerant to an acute heat stress,
      they were also more sensitive to prolonged exposure to less stressful
      temperatures, supporting a trade-off between acute and chronic heat tolerances.
      Conversely, developmental plasticity did not affect CT(max) but increased the
      tolerance to chronic heat exposition. The patterns observed from the TDT curves
      help to understand why the relationship between heat tolerance and latitude
      depends on the methodology used and, therefore, these curves provide a more
      complete and reliable measurement of heat tolerance.

PMID- 26292978
TI  - Parainflammation, chronic inflammation, and age-related macular degeneration.
AB  - Inflammation is an adaptive response of the immune system to noxious insults to
      maintain homeostasis and restore functionality. The retina is considered an
      immune-privileged tissue as a result of its unique anatomic and physiologic
      properties. During aging, the retina suffers from a low-grade chronic oxidative
      insult, which sustains for decades and increases in level with advancing age. As
      a result, the retinal innate-immune system, particularly microglia and the
      complement system, undergoes low levels of activation (parainflammation). In many
      cases, this parainflammatory response can maintain homeostasis in the healthy
      aging eye. However, in patients with age-related macular degeneration, this
      parainflammatory response becomes dysregulated and contributes to macular damage.
      Factors contributing to the dysregulation of age-related retinal parainflammation
      include genetic predisposition, environmental risk factors, and old age.
      Dysregulated parainflammation (chronic inflammation) in age-related macular
      degeneration damages the blood retina barrier, resulting in the breach of retinal
      immune privilege, leading to the development of retinal lesions. This review
      discusses the basic principles of retinal innate-immune responses to endogenous
      chronic insults in normal aging and in age-related macular degeneration and
      explores the difference between beneficial parainflammation and the detrimental
      chronic inflammation in the context of age-related macular degeneration. 

PMID- 26292983
TI  - Functional swallowing outcomes following treatment for oropharyngeal carcinoma: a
      systematic review of the evidence comparing trans-oral surgery versus non
      surgical management.
AB  - BACKGROUND: Trans-oral surgical and non-surgical management options for
      oropharyngeal squamous cell carcinoma (OPSCC) appear to offer similar survival
      outcomes. Functional outcomes, in particular swallowing, have become of
      increasing interest in the debate regarding treatment options. Contemporary
      reviews on function following treatment frequently include surrogate markers and
      limit the value of comparative analysis. OBJECTIVES OF REVIEW: A systematic
      review was performed to establish whether direct comparisons of swallowing
      outcomes could be made between trans-oral surgical approaches (trans-oral laser
      microsurgery (TLM)/trans-oral robotic surgery (TORS)) and (chemo)radiotherapy
      ((C)RT). TYPE OF REVIEW: Systematic review. SEARCH STRATEGY: MEDLINE, Embase and
      Cochrane databases were interrogated using the following MeSH terms:
      antineoplastic protocols, chemotherapy, radiotherapy, deglutition disorders,
      swallowing, lasers, and trans-oral surgery. EVALUATION METHOD: Two authors
      performed independent systematic reviews and consensus was sought if opinions
      differed. The WHO ICF classification was applied to generate analysis based
      around body functions and structure, activity limitations and participation
      restriction. RESULTS: Thirty-seven citations were included in the analysis.
      Twenty-six papers reported the outcomes for OPSCC treatment following primary
      (C)RT in 1377 patients, and 15 papers following contemporary trans-oral
      approaches in 768 patients. Meta-analysis was not feasible due to varying
      methodology and heterogeneity of outcome measures. Instrumental swallowing
      assessments were presented in 13/26 (C)RT versus 2/15 TLM/TORS papers. However,
      reporting methods of these studies were not standardised. This variety of outcome
      measures and the wide-ranging intentions of authors applying the measures in
      individual studies limit any practical direct comparisons of the effects of
      treatment on swallowing outcomes between interventions. CONCLUSIONS: From the
      current evidence, no direct comparisons could be made of swallowing outcomes
      between the surgical and non-surgical modalities. Swallowing is a
      multidimensional construct, and the range of assessments utilised by authors
      reflects the variety of available reporting methods. The MD Anderson Dysphagia
      Inventory is a subjective measure that allows limited comparison between the
      currently available heterogeneous data, and is explored in detail. The findings
      highlight that further research may identify the most appropriate tools for
      measuring swallowing in patients with OPSCC. Consensus should allow their
      standardised integration into future studies and randomised control trials.

PMID- 26292982
TI  - Further evidence for sustained systemic inflammation in xenograft recipients
      (SIXR).
AB  - INTRODUCTION: In pig-to-baboon heart/artery patch transplantation models,
      adequate costimulation blockade prevents a T-cell response. After heart
      transplantation, coagulation dysfunction (thrombocytopenia, reduced fibrinogen,
      increased D-dimer) and inflammation (increased C-reactive protein [CRP]) develop.
      We evaluated whether coagulation dysfunction and/or inflammation can be detected
      following pig artery patch transplantation. METHODS: Baboons received heart (n =
      8) or artery patch (n = 16) transplants from genetically engineered pigs and a
      costimulation blockade-based regimen. Heart grafts functioned for 15-130 days.
      Artery recipients were euthanized after 28-84 days. Platelet counts, fibrinogen,
      D-dimer, and CRP were measured. RESULTS: Thrombocytopenia and reduced fibrinogen
      developed only in recipients of hearts not expressing a coagulation-regulatory
      protein (n = 4), but not in other heart or patch recipients. However, in heart
      recipients (n = 8), there were sustained increases in D-dimer (<0.5 to 1.9 ug/ml
      [P < 0.01]) and CRP (0.26-2.2 mg/dl [P < 0.01]). In recipients of artery patches,
      there were also sustained increases in D-dimer (<0.5 to 1.4 ug/ml [P < 0.01]) and
      CRP (0.26 to 1.5 mg/dl [P < 0.001]). An IL-6R antagonist suppressed the increase
      in CRP, but not D-dimer. CONCLUSION: The pig artery patch model has proved
      valuable for determining immunosuppressive regimens that prevent sensitization to
      pig antigens. This model also provides information on the sustained systemic
      inflammation in xenograft recipients (SIXR). An IL-6R antagonist may help
      suppress this response.

PMID- 26292984
TI  - Mouse Models of Hepatitis B Virus Pathogenesis.
AB  - The host range of hepatitis B virus (HBV) is limited to humans and chimpanzees.
      As discussed in the literature, numerous studies in humans and chimpanzees have
      generated a great deal of information on the mechanisms that cause viral
      clearance, viral persistence, and disease pathogenesis during acute or chronic
      HBV infection. Relevant pathogenetic studies have also been performed in those
      few species representing natural hosts of hepadnaviruses that are related to HBV,
      such as the woodchuck hepatitis virus and the duck hepatitis virus. Further
      insight has been gained from multidisciplinary studies in transgenic or humanized
      chimeric mouse models expressing and/or replicating HBV to varying degrees. We
      provide here a concise summary of the available HBV mouse models as well as of
      the contributions of these models to our understanding of HBV pathogenesis. 

PMID- 26292985
TI  - Transmission and Institutional Infection Control of Tuberculosis.
AB  - Tuberculosis (TB) transmission control in institutions is evolving with increased
      awareness of the rapid impact of treatment on transmission, the importance of the
      unsuspected, untreated case of transmission, and the advent of rapid molecular
      diagnostics. With active case finding based on cough surveillance and rapid drug
      susceptibility testing, in theory, it is possible to be reasonably sure that no
      patient enters a facility with undiagnosed TB or drug resistance. Droplet nuclei
      transmission of TB is reviewed with an emphasis on risk factors relevant to
      control. Among environmental controls, natural ventilation and upper-room
      ultraviolet germicidal ultraviolet air disinfection are the most cost-effective
      choices, although high-volume mechanical ventilation can also be used. Room air
      cleaners are generally not recommended. Maintenance is required for all
      engineering solutions. Finally, personal protection with fit-tested respirators
      is used in many situations where administrative and engineering methods cannot
      assure protection. 

PMID- 26292987
TI  - Patentability of Stem Cells in the United States.
AB  - Until recently, the patentability of stem cells was well established within the
      judicial and statutory framework in the United States. However, the shifting
      landscape of patent law, particularly with regard to patent-eligible subject
      matter under 35 U.S.C. S101, presents new challenges to the patentability of stem
      cells. In this paper, we discuss the legal precedent that paved the way for stem
      cell patents, including Diamond v. Chakrabarty and In re Bergy. Additionally, we
      review recent Supreme Court cases and recent guidance issued by the U.S. Patent
      and Trademark Office that impose new limitations on patent-eligible subject
      matter and thereby threaten the patentability of stem cells in the United States.

PMID- 26292986
TI  - Molecular Mechanisms of Preeclampsia.
AB  - Preeclampsia is a pregnancy-specific disease characterized by new onset
      hypertension and proteinuria after 20 wk of gestation. It is a leading cause of
      maternal and fetal morbidity and mortality worldwide. Exciting discoveries in the
      last decade have contributed to a better understanding of the molecular basis of
      this disease. Epidemiological, experimental, and therapeutic studies from several
      laboratories have provided compelling evidence that an antiangiogenic state owing
      to alterations in circulating angiogenic factors leads to preeclampsia. In this
      review, we highlight the role of key circulating antiangiogenic factors as
      pathogenic biomarkers and in the development of novel therapies for preeclampsia.

PMID- 26292989
TI  - Predictive Value of Estimated Tumor Volume Measured by Ultrasonography for Occult
      Central Lymph Node Metastasis in Papillary Thyroid Carcinoma.
AB  - The clinical and prognostic value of tumor volume in various solid tumors has
      been investigated. However, there have been few studies on the clinical impact of
      tumor volume in papillary thyroid carcinoma (PTC). This study was performed to
      investigate the predictive value of estimated tumor volume measured by
      ultrasonography for occult central neck metastasis (OCNM) of PTC. A total of 264
      patients with clinically node-negative PTC on ultrasonography and computed
      tomography who underwent total thyroidectomy in conjunction with at least
      ipsilateral prophylactic central neck dissection were enrolled in this study.
      Tumor volume was derived with the formula used to calculate ellipsoids from two
      orthogonal scans during 2-D ultrasonography at initial aspiration biopsy. We
      retrospectively evaluated demographic characteristics, pre-operative
      ultrasonographic features (tumor size, volume and multifocality) and pathologic
      results. The OCNM rate was 35.6%; estimated tumor volume was used to predict OCNM
      (p = 0.035). At 0.385 mL, sensitivity and specificity were 51.1% and 66.5%, and
      the area under the curve for OCNM detection was 0.610. In multivariate analysis,
      tumor volume, but not size, was an independent predictive factor for OCNM (odds
      ratio = 1.83, p = 0.029). The other factors were extrathyroidal extension (odds
      ratio = 2.39, p = 0.004) and male gender (odds ratio = 3.90, p < 0.001). The
      estimated tumor volume of PTC measured by ultrasonography could be a pre
      operative predictor of OCNM.

PMID- 26292990
TI  - Domestic Homicide: Neuropsychological Profiles of Murderers Who Kill Family
      Members and Intimate Partners.
AB  - Domestic homicide is the most extreme form of domestic violence and one of the
      most common types of homicide. The objective was to examine differences between
      spontaneous domestic homicide and nondomestic homicide offenders regarding
      demographics, psychiatric history, crime characteristics, and neuropsychological
      status, utilizing neuropsychological test data from forensic examinations of 153
      murderers. Using standard crime classification criteria, 33% committed
      spontaneous domestic homicides (SDH) and 61% committed nondomestic homicides
      (NDH). SDH offenders were more likely to manifest psychotic disorders, but less
      likely to be diagnosed with antisocial personality disorder or to have prior
      felony convictions. SDH offenders manifested significantly worse
      neuropsychological impairments than NDH offenders. The mean number of victims was
      lower for the SDH than the NDH group and only 14% of SDH offenders used a
      firearm, whereas 59% of NDH offenders used a firearm. These findings corroborate
      the notion that spontaneous domestic homicide may represent a discernible
      criminological phenotype. 

PMID- 26292988
TI  - Integrative review on the non-invasive management of lower urinary tract symptoms
      in men following treatments for pelvic malignancies.
AB  - AIM: To develop a non-invasive management strategy for men with lower urinary
      tract symptoms (LUTS) after treatment for pelvic cancer, that is suitable for use
      in a primary healthcare context. METHODS: PubMed literature searches of LUTS
      management in this patient group were carried out, together with obtaining a
      consensus of management strategies from a panel of authors for the management of
      LUTS from across the UK. RESULTS: Data from 41 articles were investigated and
      collated. Clinical experience was sought from authors where there was no clinical
      evidence. The findings discussed in this paper confirm that LUTS after the cancer
      treatment can significantly impair men's quality of life. While many men recover
      from LUTS spontaneously over time, a significant proportion require long-term
      management. Despite the prevalence of LUTS, there is a lack of consensus on best
      management. This article offers a comprehensive treatment algorithm to manage
      patients with LUTS following pelvic cancer treatment. CONCLUSION: Based on
      published research literature and clinical experience, recommendations are
      proposed for the standardisation of management strategies employed for men with
      LUTS after the pelvic cancer treatment. In addition to implementing the
      algorithm, understanding the rationale for the type and timing of LUTS management
      strategies is crucial for clinicians and patients.

PMID- 26292991
TI  - The neuronal component of gray matter damage in multiple sclerosis: A [(11)
      C]flumazenil positron emission tomography study.
AB  - OBJECTIVE: Using positron emission tomography (PET) with [(11) C]flumazenil
      ([(11) C]FMZ), an antagonist of the central benzodiazepine site located within
      the GABAA receptor, we quantified and mapped neuronal damage in the gray matter
      (GM) of patients with multiple sclerosis (MS) at distinct disease stages. We
      investigated the relationship between neuronal damage and white matter (WM)
      lesions and evaluated the clinical relevance of this neuronal PET metric.
      METHODS: A cohort of 18 MS patients (9 progressive and 9 relapsing-remitting) was
      compared to healthy controls and underwent neurological and cognitive
      evaluations, high-resolution dynamic [(11) C]FMZ PET imaging and brain magnetic
      resonance imaging. [(11) C]FMZ binding was estimated using the partial saturation
      protocol providing voxel-wise absolute quantification of GABAA receptor
      concentration. PET data were evaluated using a region of interest (ROI) approach
      as well as on a vertex-by-vertex basis. RESULTS: [(11) C]FMZ binding was
      significantly decreased in the cortical GM of MS patients, compared to controls (
      10%). Cortical mapping of benzodiazepine receptor concentration ([(11) C]FMZ
      Bmax) revealed significant intergroup differences in the bilateral parietal
      cortices and right frontal areas. ROI analyses taking into account GM volume
      changes showed extensive decrease in [(11) C]FMZ binding in bilateral parietal,
      cingulate, and insular cortices as well as in the thalami, amygdalae, and
      hippocampi. These changes were significant in both progressive and relapsing
      remitting forms of the disease and correlated with WM T2-weighted lesion load.
      [(11) C]FMZ cortical binding correlated with cognitive performance.
      INTERPRETATION: This pilot study showed that PET with [(11) C]FMZ could be a
      promising and sensitive quantitative marker to assess and map the neuronal
      substrate of GM pathology in MS.

PMID- 26292992
TI  - Know your limits? Climate extremes impact the range of Scots pine in unexpected
      places.
AB  - BACKGROUND AND AIMS: Although extreme climatic events such as drought are known
      to modify forest dynamics by triggering tree dieback, the impact of extreme cold
      events, especially at the low-latitude margin ('rear edge') of species
      distributional ranges, has received little attention. The aim of this study was
      to examine the impact of one such extreme cold event on a population of Scots
      pine (Pinus sylvestris) along the species' European southern rear-edge range
      limit and to determine how such events can be incorporated into species
      distribution models (SDMs). METHODS: A combination of dendrochronology and field
      observation was used to quantify how an extreme cold event in 2001 in eastern
      Spain affected growth, needle loss and mortality of Scots pine. Long-term
      European climatic data sets were used to contextualize the severity of the 2001
      event, and an SDM for Scots pine in Europe was used to predict climatic range
      limits. KEY RESULTS: The 2001 winter reached record minimum temperatures
      (equivalent to the maximum European-wide diurnal ranges) and, for trees already
      stressed by a preceding dry summer and autumn, this caused dieback and large
      scale mortality. Needle loss and mortality were particularly evident in south
      facing sites, where post-event recovery was greatly reduced. The SDM predicted
      European Scots pine distribution mainly on the basis of responses to maximum and
      minimum monthly temperatures, but in comparison with this the observed effects of
      the 2001 cold event at the southerly edge of the range limit were unforeseen.
      CONCLUSIONS: The results suggest that in order to better forecast how
      anthropogenic climate change might affect future forest distributions,
      distribution modelling techniques such as SDMs must incorporate climatic
      extremes. For Scots pine, this study shows that the effects of cold extremes
      should be included across the entire distribution margin, including the southern
      'rear edge', in order to avoid biased predictions based solely on warmer climatic
      scenarios.

PMID- 26292993
TI  - The developmental genetics of biological robustness.
AB  - BACKGROUND: Living organisms are continuously confronted with perturbations, such
      as environmental changes that include fluctuations in temperature and nutrient
      availability, or genetic changes such as mutations. While some developmental
      systems are affected by such challenges and display variation in phenotypic
      traits, others continue consistently to produce invariable phenotypes despite
      perturbation. This ability of a living system to maintain an invariable phenotype
      in the face of perturbations is termed developmental robustness. Biological
      robustness is a phenomenon observed across phyla, and studying its mechanisms is
      central to deciphering the genotype-phenotype relationship. Recent work in yeast,
      animals and plants has shown that robustness is genetically controlled and has
      started to reveal the underlying mechinisms behind it. SCOPE AND CONCLUSIONS:
      Studying biological robustness involves focusing on an important property of
      developmental traits, which is the phenotypic distribution within a population.
      This is often neglected because the vast majority of developmental biology
      studies instead focus on population aggregates, such as trait averages. By
      drawing on findings in animals and yeast, this Viewpoint considers how studies on
      plant developmental robustness may benefit from strict definitions of what is the
      developmental system of choice and what is the relevant perturbation, and also
      from clear distinctions between gene effects on the trait mean and the trait
      variance. Recent advances in quantitative developmental biology and high
      throughput phenotyping now allow the design of targeted genetic screens to
      identify genes that amplify or restrict developmental trait variance and to study
      how variation propagates across different phenotypic levels in biological
      systems. The molecular characterization of more quantitative trait loci affecting
      trait variance will provide further insights into the evolution of genes
      modulating developmental robustness. The study of robustness mechanisms in
      closely related species will address whether mechanisms of robustness are
      evolutionarily conserved.

PMID- 26292994
TI  - Development and evolution of extreme synorganization in angiosperm flowers and
      diversity: a comparison of Apocynaceae and Orchidaceae.
AB  - BACKGROUND AND AIMS: Apocynaceae and Orchidaceae are two angiosperm families with
      extreme flower synorganization. They are unrelated, the former in eudicots, the
      latter in monocots, but they converge in the formation of pollinia and
      pollinaria, which do not occur in any other angiosperm family, and for which
      extreme synorganization of floral organs is a precondition. In each family
      extensive studies on flower development and evolution have been performed;
      however, newer comparative studies focusing on flower synorganization and
      involving both families together are lacking. SCOPE: For this study an extensive
      search through the morphological literature has been conducted. Based on this and
      my own studies on flowers in various Apocynaceae and Orchidaceae and complex
      flowers in other angiosperms with scanning electron microscopy and with microtome
      section series, a review on convergent floral traits in flower development and
      architecture in the two families is presented. KEY FINDINGS: There is a tendency
      of protracted development of synorganized parts in Apocynaceae and Orchidaceae
      (development of synorganization of two or more organs begins earlier the more
      accentuated it is at anthesis). Synorganization (or complexity) also paves the
      way for novel structures. One of the most conspicuous such novel structures in
      Apocynaceae is the corona, which is not the product of synorganization of
      existing organs; however, it is probably enhanced by synorganization of other,
      existing, floral parts. In contrast to synorganized parts, the corona appears
      developmentally late. CONCLUSIONS: Synorganization of floral organs may lead to a
      large number of convergences in clades that are only very distantly related. The
      convergences that have been highlighted in this comparative study should be
      developmentally investigated directly in parallel in future studies.

PMID- 26292996
TI  - Distal Communication by Chimpanzees (Pan troglodytes): Evidence for Common
      Ground?
AB  - van der Goot et al. (2014) proposed that distal, deictic communication indexed
      the appreciation of the psychological state of a common ground between a signaler
      and a receiver. In their study, great apes did not signal distally, which they
      construed as evidence for the human uniqueness of a sense of common ground. This
      study exposed 166 chimpanzees to food and an experimenter, at an angular
      displacement, to ask, "Do chimpanzees display distal communication?" Apes were
      categorized as (a) proximal or (b) distal signalers on each of four trials. The
      number of chimpanzees who communicated proximally did not statistically differ
      from the number who signaled distally. Therefore, contrary to the claim by van
      der Goot et al., apes do communicate distally.

PMID- 26292995
TI  - Importance of the alternative oxidase (AOX) pathway in regulating cellular redox
      and ROS homeostasis to optimize photosynthesis during restriction of the
      cytochrome oxidase pathway in Arabidopsis thaliana.
AB  - BACKGROUND AND AIMS: The importance of the alternative oxidase (AOX) pathway,
      particularly AOX1A, in optimizing photosynthesis during de-etiolation, under
      elevated CO2, low temperature, high light or combined light and drought stress is
      well documented. In the present study, the role of AOX1A in optimizing
      photosynthesis was investigated when electron transport through the cytochrome c
      oxidase (COX) pathway was restricted at complex III. METHODS: Leaf discs of wild
      type (WT) and aox1a knock-out mutants of Arabidopsis thaliana were treated with
      antimycin A (AA) under growth-light conditions. To identify the impact of AOX1A
      deficiency in optimizing photosynthesis, respiratory O2 uptake and photosynthesis
      related parameters were measured along with changes in redox couples, reactive
      oxygen species (ROS), lipid peroxidation and expression levels of genes related
      to respiration, the malate valve and the antioxidative system. KEY RESULTS: In
      the absence of AA, aox1a knock-out mutants did not show any difference in
      physiological, biochemical or molecular parameters compared with WT. However,
      after AA treatment, aox1a plants showed a significant reduction in both
      respiratory O2 uptake and NaHCO3-dependent O2 evolution. Chlorophyll fluorescence
      and P700 studies revealed that in contrast to WT, aox1a knock-out plants were
      incapable of maintaining electron flow in the chloroplastic electron transport
      chain, and thereby inefficient heat dissipation (low non-photochemical quenching)
      was observed. Furthermore, aox1a mutants exhibited significant disturbances in
      cellular redox couples of NAD(P)H and ascorbate (Asc) and consequently
      accumulation of ROS and malondialdehyde (MDA) content. By contrast, WT plants
      showed a significant increase in transcript levels of CSD1, CAT1, sAPX, COX15 and
      AOX1A in contrast to aox1a mutants. CONCLUSIONS: These results suggest that AOX1A
      plays a significant role in sustaining the chloroplastic redox state and
      energization to optimize photosynthesis by regulating cellular redox homeostasis
      and ROS generation when electron transport through the COX pathway is disturbed
      at complex III.

PMID- 26292998
TI  - Antimicrobial Effects of Blueberry, Raspberry, and Strawberry Aqueous Extracts
      and their Effects on Virulence Gene Expression in Vibrio cholerae.
AB  - The antimicrobial effects of aqueous extracts of blueberry, raspberry, and
      strawberry on 13 pathogenic bacteria were evaluated. The minimum inhibitory
      concentrations and minimum bactericidal concentrations of the extracts were
      determined before and after neutralization to pH 7.03 +/- 0.15. Both Gram
      positive and Gram-negative pathogenic bacteria were selectively inhibited by the
      non-neutralized berries. Blueberry was the best inhibitor, and Vibrio and
      Listeria were the most sensitive bacteria. After neutralization, blueberry
      affected only Vibrio and Listeria, whereas the antimicrobial activities of
      raspberry and strawberry were abolished. The total contents of phenolics,
      flavonoids, and proanthocyanidins in the extracts were measured with colorimetric
      methods and were highest in strawberry, followed by raspberry, and then
      blueberry. We also studied the effects of sub-bactericidal concentrations of the
      three berry extracts on virulence gene expression in Vibrio cholerae. Real-time
      quantitative reverse transcription-polymerase chain reaction revealed that the
      three berry extracts effectively repressed the transcription of the tcpA gene.
      Raspberry also repressed the transcription of the ctxA gene, whereas blueberry
      and strawberry did not. However, the three berry extracts did not affect the
      transcription of toxT. These results suggest that the three berry extracts exert
      potent antimicrobial effects and inhibit the expression of the virulence factors
      of V. cholerae.

PMID- 26292999
TI  - The mandibles of castrated male rhesus macaques (Macaca mulatta): The effects of
      orchidectomy on bone and teeth.
AB  - OBJECTIVES: The objectives of this study were to evaluate the long-term effects
      of orchidectomy and low testosterone on the craniofaciodental development and
      maintenance of skeletal and oral health in rhesus macaques. MATERIALS AND
      METHODS: Mandibles of four castrated and intact age-matched male rhesus monkeys
      (Macaca mulatta) from Cayo Santiago were compared for mandibular morphology and
      teeth, abnormalities, pathology, and cortical bone thickness and density using a
      digital sliding caliper and analysis of three-dimensional X-ray images. RESULTS:
      Although all four castrates were generally comparable to intact males in overall
      mandible and teeth size, there were some significant differences. In the
      castrates, (1) the distance between the two rami was narrower than in intact
      males leading to a relatively narrower and longer face; (2) both the mandibular
      body and ramus had thinner cortical bone leading to less total bone mass; and (3)
      the canines and molar teeth were slender with lower and less robust tooth cusps.
      In addition, the alveolar bone of two geriatric castrates was greatly receded
      with signs of periodontitis more severe than in intact aged males. Old castrates
      also had severe temporomandibular joint osteoarthritis. DISCUSSION: The findings
      suggest the importance of testosterone in craniofaciodental development, and
      maintenance of skeletal and oral health in male macaques. These results suggest
      that dental health professionals might want to include in their medical history
      questionnaires whether or not male patients have taken hormone (testosterone)
      replacement therapy.

PMID- 26293000
TI  - Impact of rituximab maintenance and maintenance schedule on prognosis in first
      line treatment of follicular lymphoma. Retrospective analysis from Czech Lymphoma
      Study Group (CLSG) database.
AB  - Rituximab maintenance (RM) improves time to progression (PFS) in advanced
      follicular lymphoma (FL), but the impact of various RM schedules remains unknown.
      This study performed a retrospective evaluation of RM given for up to 2 years vs
      observation in 319 untreated FL patients (stage II-IV; grade 1-3A) responding to
      RCHOP induction and a comparison of two different RM schedules (RM8=eight doses
      given every 3 months and RM12=12 doses given every 2 months). A total of 183
      patients received RM and 136 patients were observed; 5-year PFS was better in the
      RM arm, 74.1% vs 52.3% (p<0.001), which was projected in 5-year OS 93.8% vs 87.5%
      (p=0.005). However, 5-year PFS was similar in both the RM8 (n=54) and RM12 (n=56)
      arms. In the first line, RM significantly prolongs PFS and OS in FL, but
      different RM schedules bring a similar benefit.

PMID- 26293001
TI  - Validation of an integral conceptual model of frailty in older residents of
      assisted living facilities.
AB  - OBJECTIVE: The aim of this cross-sectional study was to examine the validity of
      an integral model of the associations between life-course determinants,
      disease(s), frailty, and adverse outcomes in older persons who are resident in
      assisted living facilities. METHODS: Between June 2013 and May 2014 seven
      assisted living facilities were contacted. A total of 221 persons completed the
      questionnaire on life-course determinants, frailty (using the Tilburg Frailty
      Indicator), self-reported chronic diseases, and adverse outcomes disability,
      quality of life, health care utilization, and falls. Adverse outcomes were
      analyzed with sequential (logistic) regression analyses. RESULTS: The integral
      model is partially validated. Life-course determinants and disease(s) affected
      only physical frailty. All three frailty domains (physical, psychological,
      social) together affected disability, quality of life, visits to a general
      practitioner, and falls. Contrary to the model, disease(s) had no effect on
      adverse outcomes after controlling for frailty. Life-course determinants affected
      adverse outcomes, with unhealthy lifestyle having consistent negative effects,
      and women had more disability, scored lower on physical health, and received more
      personal and informal care after controlling for all other predictors.
      CONCLUSION: The integral model of frailty is less useful for predicting adverse
      outcomes of residents of assisted living facilities than for community-dwelling
      older persons, because these residents are much frailer and already have access
      to healthcare facilities. PRACTICAL IMPLICATIONS: The present study showed that a
      multidimensional assessment of frailty, distinguishing three domains of frailty
      (physical, psychological, social), is beneficial with respect to predicting
      adverse outcomes in residents of assisted living facilities.

PMID- 26292997
TI  - Beery VMI performance in autism spectrum disorder.
AB  - Few studies have examined the visuomotor integration (VMI) abilities of
      individuals with autism spectrum disorder (ASD). An all-male sample consisting of
      56 ASD participants (ages 3-23 years) and 36 typically developing (TD)
      participants (ages 4-26 years) completed the Beery-Buktenica Developmental Test
      of Visual-Motor Integration (Beery VMI) as part of a larger neuropsychological
      battery. Participants were also administered standardized measures of
      intellectual functioning and the Social Responsiveness Scale (SRS), which
      assesses autism and autism-like traits. The ASD group performed significantly
      lower on the Beery VMI and on all IQ measures compared to the TD group. VMI
      performance was significantly correlated with full scale IQ (FSIQ), performance
      IQ (PIQ), and verbal IQ (VIQ) in the TD group only. However, when FSIQ was taken
      into account, no significant Beery VMI differences between groups were observed.
      Only one TD participant scored 1.5 standard deviations (SDs) below the Beery VMI
      normative sample mean, in comparison to 21% of the ASD sample. As expected, the
      ASD group was rated as having significantly higher levels of social impairment on
      the SRS compared to the TD group across all major domains. However, level of
      functioning on the SRS was not associated with Berry VMI performance. These
      findings demonstrate that a substantial number of individuals with ASD experience
      difficulties compared to TD in performing VMI-related tasks, and that VMI is
      likely affected by general cognitive ability. The fact that lowered Beery VMI
      performance occurred only within a subset of individuals with ASD and did not
      correlate with SRS would indicate that visuomotor deficits are not a core feature
      of ASD, even though they present at a higher rate of impairment than observed in
      TD participants.

PMID- 26293002
TI  - Wishful thinking in preschoolers.
AB  - The current experiment sought to demonstrate the presence of wishful thinking-
      when wishes influence beliefs--in young children. A sample of 77 preschoolers
      needed to predict, eight times in a row, which of two plastic eggs, one
      containing one toy and the other containing three toys, would be drawn by a
      blinded experimenter. On the four trials in which the children could not keep the
      content of the egg drawn, they were equally likely to predict that either egg
      would be drawn. By contrast, on the four trials in which the children got to keep
      the content of the egg, they were more likely to predict that the egg with three
      toys would be drawn. Any effort the children exerted would be the same across
      conditions, so that this demonstration of wishful thinking cannot be accounted
      for by an effort heuristic. One group of children--a subgroup of the 5-year-olds-
      did not engage in wishful thinking. Children from this subgroup instead used the
      representativeness heuristic to guide their answers. This result suggests that
      having an explicit representation of the outcome inhibits children from engaging
      in wishful thinking in the same way as explicit representations constrain the
      operation of motivated reasoning in adults.

PMID- 26293003
TI  - Adult-onset photosensitivity: clinical significance and epilepsy syndromes
      including idiopathic (possibly genetic) photosensitive occipital epilepsy.
AB  - To evaluate the clinical associations of adult-onset photosensitivity, we studied
      the clinical and EEG data of patients who were referred due to a possible first
      seizure and who had a photoparoxysmal response on their EEG. Patients with
      clinical evidence of photosensitivity before the age of 20 were excluded. Of a
      total of 30 patients, four had acute symptomatic seizures, two had vasovagal
      syncope, and 24 were diagnosed with epilepsy. Nine of the 24 patients had
      idiopathic (genetic) generalized epilepsies and predominantly generalized
      photoparoxysmal response, but also rare photically-induced seizures, while 15 had
      exclusively, or almost exclusively, reflex photically-induced occipital seizures
      with frequent secondary generalization and posterior photoparoxysmal response.
      Other important differences included a significantly older age at seizure onset
      and paucity of spontaneous interictal epileptic discharges in patients with
      photically-induced occipital seizures; only a quarter of these had occasional
      occipital spikes, in contrast to the idiopathic (genetic) generalized epilepsy
      patients with typically generalized epileptic discharges. On the other hand, both
      groups shared a positive family history of epilepsy, common seizure threshold
      modulators (such as tiredness and sleep deprivation), normal neurological
      examination and MRI, a generally benign course, and good response to valproic
      acid. We demonstrated that photosensitivity can first occur in adult life and
      manifest, either as idiopathic (possibly genetic) photosensitive occipital
      epilepsy with secondary generalization or as an EEG, and less often, a
      clinical/EEG feature of idiopathic (genetic) generalized epilepsies.
      Identification of idiopathic photosensitive occipital epilepsy fills a diagnostic
      gap in adult first-seizure epileptology and is clinically important because of
      its good response to antiepileptic drug treatment and fair prognosis. 

PMID- 26293004
TI  - New treatments for levodopa-induced motor complications.
AB  - Levodopa (l-dopa)-induced motor complications, including motor fluctuations and
      dyskinesia, affect almost all patients with Parkinson's disease (PD) at some
      point during the disease course, with relevant implications in global health
      status. Various dopaminergic and nondopaminergic pharmacological approaches as
      well as more invasive strategies including devices and functional surgery are
      available to manage such complications. In spite of undisputable improvements
      during the last decades, many patients remain significantly disabled, and a fully
      satisfying management of l-dopa-induced motor complications is still an important
      unmet need of PD therapy. This article reviews the recent trial results published
      from 2013 to April 2015 about pharmacological and nonpharmacological
      interventions to treat motor complications. Randomized controlled trials
      conducted in patients suffering from already established complications showed
      that new levodopa (l-dopa) formulations such as intrajejunal l-dopa-carbidopa
      infusion and bilayered extended-release l-dopa-carbidopa (IPX066) can improve
      motor fluctuations. Positive results were also obtained with a new monoamine
      oxidase B (MAO-B) inhibitor (safinamide) and a catechol-O-methyltransferase COMT
      inhibitor (opicapone). Pilot data suggest that new formulations of dopamine
      agonists (inhaled apomorphine) are also of potential interest. The development of
      novel nondopaminergic adenosine A2A antagonists (istradefylline, preladenant, and
      tozadenant) to treat motor fluctuations showed conflicting results in phase 2 and
      phase 3 trials. For dyskinesia, trials with new amantadine extended-release
      formulations confirmed the interest of the glutamatergic N-methyl-d-aspartate
      (NMDA) antagonist approach. Positive pilot antidyskinetic effects were also
      recently reported using serotonin agents such as eltoprazine and glutamate mGluR5
      modulators such as mavoglurant. However, the translation to clinical practice of
      such innovative concepts remains challenging, because subsequent phase 2 trials
      conducted to confirm the antidyskynetic effects of mavoglurant failed, leading to
      the interruption of the development of this compound for this indication.

PMID- 26293006
TI  - Celiac Disease and Type 1 Diabetes in Adults: Is This a High-Risk Group for
      Screening?
AB  - The association between celiac disease (CD), an autoimmune condition involving
      intestinal inflammation related to gluten ingestion, and type 1 diabetes has long
      been recognized. CD prevalence rates 4 to 6 times greater in adults with type 1
      diabetes than in the general population. Much of the existing literature focuses
      on important implications related to the impact of a gluten-free diet on short
      term outcomes in metabolic control and quality of life. Canadian Diabetes
      Association guidelines recommend targeted CD screening in patients with type 1
      diabetes who have classic symptoms, such as abdominal pain, bloating, diarrhea,
      unexplained weight loss or labile metabolic control; however, a significant
      proportion (40% to 60%) of patients may have mild or absent symptoms. Recent
      evidence suggests that adult patients with both conditions are at higher risk for
      diabetes microvascular comorbidities, increased mortality and impaired bone
      health if the CD is untreated. The purpose of this review is to describe the
      association between CD and type 1 diabetes and to summarize recent literature
      that evaluates risks in patients with both conditions. 

PMID- 26293007
TI  - Obliterative Endoaneurysmorrhaphy with Stent Graft Preservation for Treatment of
      Type II Progressive Endoleak.
AB  - OBJECTIVE/BACKGROUND: Persistent type II endoleak (EL II) with sac enlargement
      after endovascular repair of abdominal aortic aneurysm requires treatment to
      prevent rupture. Embolization is not always effective. Conversion to open repair
      with stent graft (SG) explantation is a high risk option. The aim of this study
      was to evaluate the feasibility and immediate results of an alternative technique
      combining obliterative endoaneurysmorrhaphy (OEA) with SG preservation. METHODS:
      The open surgical technique combined sacotomy, ligation of all patent back
      bleeding vessels and SG preservation. The aneurysmal shell was tightly closed
      over the SG to protect it from the intestines. An intra-aortic occlusion balloon
      was used when clamping was required. RESULTS: Twelve patients were treated with
      the OEA technique at Amiens University Hospital. All 12 procedures were
      successful. Four patients had previously undergone unsuccessful transarterial or
      translumbar embolization. Aortic clamping was performed in four cases. No SG
      migration or graft dislocation was observed. Follow up computed tomography scan
      at a median of 12 months showed shrinkage of the aneurysm sac with stable
      diameters and no recurrence of EL II in all cases. CONCLUSION: The OEA technique
      is an alternative option for the treatment of progressive EL II, which can be
      particularly useful after failure of embolization.

PMID- 26293008
TI  - Accurate detection of binary toxin producer from Clostridium difficile by matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry.
AB  - Thirsty-six binary toxin producers were detected with 2 genotypes (cdtA(+) and
      cdtB(+)) among 265 Clostridium difficile isolates by multiplex PCR. The rate of
      accurate differentiation between these 2 genotypes was 100% by 6-peak cluster
      analysis of spectra generated by Bruker Biotyper matrix-assisted laser desorption
      ionization/time-of-flight mass spectrometry. 

PMID- 26293005
TI  - Current and future antimicrobial treatment of gonorrhoea - the rapidly evolving
      Neisseria gonorrhoeae continues to challenge.
AB  - Neisseria gonorrhoeae has developed antimicrobial resistance (AMR) to all drugs
      previously and currently recommended for empirical monotherapy of gonorrhoea. In
      vitro resistance, including high-level, to the last option ceftriaxone and
      sporadic failures to treat pharyngeal gonorrhoea with ceftriaxone have emerged.
      In response, empirical dual antimicrobial therapy (ceftriaxone 250-1000 mg plus
      azithromycin 1-2 g) has been introduced in several particularly high-income
      regions or countries. These treatment regimens appear currently effective and
      should be considered in all settings where local quality assured AMR data do not
      support other therapeutic options. However, the dual antimicrobial regimens,
      implemented in limited geographic regions, will not entirely prevent resistance
      emergence and, unfortunately, most likely it is only a matter of when, and not
      if, treatment failures with also these dual antimicrobial regimens will emerge.
      Accordingly, novel affordable antimicrobials for monotherapy or at least
      inclusion in new dual treatment regimens, which might need to be considered for
      all newly developed antimicrobials, are essential. Several of the recently
      developed antimicrobials deserve increased attention for potential future
      treatment of gonorrhoea. In vitro activity studies examining collections of
      geographically, temporally and genetically diverse gonococcal isolates, including
      multidrug-resistant strains particularly with resistance to ceftriaxone and
      azithromycin, are important. Furthermore, understanding of effects and biological
      fitness of current and emerging (in vitro induced/selected and in vivo emerged)
      genetic resistance mechanisms for these antimicrobials, prediction of resistance
      emergence, time-kill curve analysis to evaluate antibacterial activity,
      appropriate mice experiments, and correlates between genetic and phenotypic
      laboratory parameters, and clinical treatment outcomes, would also be valuable.
      Subsequently, appropriately designed, randomized controlled clinical trials
      evaluating efficacy, ideal dose, toxicity, adverse effects, cost, and
      pharmacokinetic/pharmacodynamics data for anogenital and, importantly, also
      pharyngeal gonorrhoea, i.e. because treatment failures initially emerge at this
      anatomical site. Finally, in the future treatment at first health care visit will
      ideally be individually-tailored, i.e. by novel rapid phenotypic AMR tests and/or
      genetic point of care AMR tests, including detection of gonococci, which will
      improve the management and public health control of gonorrhoea and AMR.
      Nevertheless, now is certainly the right time to readdress the challenges of
      developing a gonococcal vaccine.

PMID- 26293009
TI  - Summary of recent BNCT Polish programme and future plans.
AB  - In this work we present Polish achievements on the ground of BNCT research.
      Starting from preliminary built therapeutic stand at MARIA reactor going through
      designing of unique detectors for in-phantom and in-beam measurements for mixed
      radiation fields and finally coming to boron carriers synthesizing and
      examination in cellular and animal models. Now it is planned to restart research
      on boron compounds in specially designed BIMA line, to set up epithermal neutron
      irradiation facility for BNCT research and education and to improve recombination
      detectors for neutron beams characterisation. 

PMID- 26293010
TI  - Fibrin tissue adhesive for face- and necklift.
AB  - INTRODUCTION: Although available for decades, fibrin-based tissue adhesives
      (FTAs) have enjoyed only variable popularity in aesthetic surgery since their
      introduction in the 1980s. Whilst benefits in facelift surgery have been reported
      for a range of measures, including expanding haematoma, oedema and ecchymosis,
      irrefutable evidence has not yet been forthcoming. We instigated a prospective
      study to test the hypothesis that an underappreciated property of FTA, namely its
      ability to distribute tension, would reduce complications and revision due to
      early relapse. PATIENTS AND METHODS: The study group comprised 100 consecutive
      facelifts with FTA. The comparative group comprised the immediate preceding 100
      patients who underwent similar interventions, but with drains instead of FTA. All
      surgery was undertaken by the senior author using standard techniques and
      statistical analysis employing Fisher's exact test. RESULTS: The groups were
      comparable in age, gender distribution, co-morbidity and declared cigarette
      smoking. Complications were recorded in 24 patients with significantly more in
      the comparative group (p = 0.048), particularly hypertrophic scarring (p =
      0.029). Although there appeared a greater prevalence of revision and cutaneous
      necrosis in the comparative group, these did not reach statistical significance.
      DISCUSSION: To the many published benefits, we can add that FTA can reduce
      complications, particularly hypertrophic scarring, and it now forms an important
      part of our facelift practice.

PMID- 26293011
TI  - Skin Cancers as Contraindication to Organ Transplantation.
AB  - The period of preparing patients for organ transplantation is a suitable time for
      dermatologic screening and examination that guarantee early diagnosis and easier
      treatment of precancerous states and skin cancers. In most cases, diagnosis of
      skin cancer in the pretransplantation period is not a contraindication to
      transplantation. Knowledge of risk factors and etiopathogenesis of skin cancers
      after transplantation make it easier to point out patients with increased risk of
      skin carcinogenesis. Patients with skin phototype I-III (Fitzpatrick
      classification) and with high cumulative doses of ultraviolet radiation have an
      increased risk of skin cancers. Patients who had skin cancers in the past should
      be carefully examined, and the skin cancer histopathology should be analyzed in
      detail. These examinations have to be done from the clinical, surgical, and
      histopathologic aspects. It helps dermatologists to estimate the risk and predict
      the patient's health after a possible organ transplantation. Basal cell carcinoma
      and squamous cell carcinoma that are present before transplantation indicate the
      possibility of similar cancer occurrence after transplantation; however, they are
      not a contraindication to transplantation after treatment of the primary foci.
      The waiting period to transplantation in the case of melanoma in situ takes 2
      years, but in more serious forms of melanoma this time is prolonged to >= 5-10
      years. Different skin cancers have a 3-year asymptomatic period to renewed
      indication for transplantation.

PMID- 26293012
TI  - Knowledge Attitudes and Behaviors About Organ Donation Among First- and Sixth
      class Medical Students: A Study From Turkey.
AB  - OBJECTIVES: The aim of this study is to determine the knowledge, attitude, and
      behaviors of Erciyes University School of Medicine students regarding organ
      donation. MATERIALS AND METHODS: This descriptive study was conducted in 2014 on
      Erciyes University School of Medicine first- and sixth-grade students via
      questionnaire. It was to be conducted on all 490 students; in total, 464 students
      were enrolled-304 from first grade and 160 from sixth grade. Data were analyzed
      using descriptive statistics, chi(2) test, and binary logistic regression
      analysis. RESULTS: The mean age was 20.9 +/- 2.8 years and it was found that
      48.9% were male, 65.5% were in first grade; 50.0% of the students who
      participated in the study were considering donating their organs and this rate is
      45.4% in the first grade and 58.8% at sixth grade. Those who donated their organs
      were 3.4% in the entire group and were 1.6% and 6.9% consequently in first and
      sixth grades. Those who are; at the sixth grade, female gender, those who feel
      themselves responsible for the donation of society, who think organ donation is
      appropriate in terms of religion and conversations within family about organ
      donations significantly want organ donation more statistically. However, grade
      and gender had no effect on wishing donating organs according to binary logistic
      regression analysis. The rate of feeling themselves responsible from the donation
      in society was 73.9% and finding organ donation appropriate in terms of religion
      was 75.6% and there wasn't significant difference between first and sixth grades.
      CONCLUSION: Although there are increases in many variables about this issue at
      sixth grade, students are unable to gain sufficient attitude and behavior about
      organ donation. Training can be planned during medical educations in terms of
      gaining attitudes and behaviors about the issue.

PMID- 26293013
TI  - Risk Behavior and Reciprocity of Organ Donation Attitudes in Young Men.
AB  - BACKGROUND: Lack of donor organs remains a major obstacle in organ
      transplantation. Our aim was to evaluate (1) the association between engaging in
      high-risk recreational activities and attitudes toward organ donation and (2) the
      degree of reciprocity between organ acceptance and donation willingness in young
      men. METHODS: A 17-item, close-ended survey was offered to male conscripts ages
      18 to 26 years in all Swiss military conscription centers. Predictors of organ
      donation attitudes were assessed in bivariate analyses and multiple logistic
      regression. Reciprocity of the intentions to accept and to donate organs was
      assessed by means of donor card status. RESULTS: In 1559 responses analyzed,
      neither motorcycling nor practicing extreme sports reached significant
      association with donor card holder status. Family communication about organ
      donation, student, or academic profession and living in a Latin linguistic region
      were predictors of positive organ donation attitudes, whereas residence in a
      German-speaking region and practicing any religion predicted reluctance.
      Significantly more respondents were willing to accept than to donate organs,
      especially among those without family communication concerning organ donation.
      CONCLUSIONS: For the first time, it was shown that high-risk recreational
      activities do not influence organ donation attitudes. Second, a considerable
      discrepancy in organ donation reciprocity was identified. We propose that
      increasing this reciprocity could eventually increase organ donation rates.

PMID- 26293014
TI  - Organ Donation Among Health Care Providers: Is Giving and Receiving Similar?
AB  - BACKGROUND: Health care providers encourage organ donation on a regular basis.
      The objective of this study was to analyze the coherence of the attitudes of
      health care providers toward organ donation, their willingness to receive organs
      and the differences among different health care practitioners and other hospital
      workers regarding to this ethical issue. METHODS: A 33-question survey was
      conducted among staff members from 9 different health care institutions in
      different sites from North and Central America. The confidential and anonymous
      questionnaire addressed personal opinions regarding organ donation as well as
      other ethical/religious issues. RESULTS: Of 858 surveys conducted, 853 were
      completed. Among the participants, physicians accounted for 21.1% (n = 180),
      nurses 37.1% (n = 317), and other hospital workers 41.7% (n = 356). Respondents
      were almost equally divided into organ donors 45.7% (n = 392) and nondonors 53.7%
      (n = 461). Doctors and nurses were significantly more likely to be organ donors
      than other hospital workers (P < .043). An overwhelming majority of responders
      would accept an organ transplant if required (90.2%; n = 774). Organ donors were
      more likely to accept an organ transplant if required than nonorgan donors (96.4%
      [n = 370] vs 88.7% [n = 400], respectively; P < .001). CONCLUSIONS: Among health
      care providers, physicians and nurses tended to be more likely to be in favor of
      organ donation. The majority of the participants were willing to accept an organ,
      and there was a statistical correlation between disposition to donation and
      willingness to receive an organ.

PMID- 26293015
TI  - Withdrawn: Simulated Donor Family Encounters at Organ Transplantation
      Coordinators In-service Training Course: Process and Impact Evaluation.
AB  - OBJECTIVE: The study was aimed at introducing the modified version of the organ
      transplantation coordinator course including simulated donor family encounters
      (SDFEs), communication skills, and evaluating the participants' opinions,
      achievement levels, and how they implemented what they learned in the course in
      their work settings. METHODS: The course was modified using the ADDIE (analysis,
      design, development, implementation, and evaluation) model and was evaluated in
      three steps: The participants' views were obtained using the course overall
      evaluation form and communication skills evaluation form, their success was
      assessed with the post-test and SDFEs evaluation form, and the effects of what
      they learned during the course on their work settings were assessed through phone
      interviews. At this step, the participants were asked to write letters about the
      targets they intended to achieve in their work settings. The letters were
      analyzed with the content analysis method, and a questionnaire consisting of 105
      targets was developed. A year later the participants were telephoned and asked to
      what extent they achieved their targets. RESULTS: The participants' satisfaction
      from the whole course was high (x: 8.65 +/- 1.06). In the communication skills
      evaluation form, the participants stated that they would mainly use their
      communication and empathy skills during donor family encounters. The
      participants' mean post-test score was high (x: 96.0 +/- 3.8). During the SDFEs,
      70% of the respondents' performance was considered sufficient. Telephone
      interviews conducted with the questionnaire revealed that 77.6% of the targets
      were fulfilled. CONCLUSION: It can be said that the course affected the
      participants in terms of implementing their knowledge and communication skills
      related to family encounters.

PMID- 26293016
TI  - Living Kidney Donor Transplantation in a Resource-limited Country: The Ivory
      Coast Experience.
AB  - Renal transplantation that offers a good quality of life still is not performed
      by the majority of countries of black Africa. We started a pilot project of renal
      transplantation in Ivory Coast 2 years ago. The present paper reports the
      preliminary results, difficulties related to the program, and perspectives
      regarding its expansion. Ten living related kidney transplantations have been
      performed over a 2-year period. Recipients and their respective donors were male.
      The mean age of the recipients was 42.8 years (22-57), and the mean age of the
      donors was 29.4 years (22-43). The mean number of mismatches was 3.2 (0-6). None
      was immunized. Recipients and donors were all EBV IgG positive and CMV IgG
      positive. All but 1 case were induced with basiliximab. The mean graft and
      patient survival time was 16.6 months (6-26). The mean cold ischemic time was
      2.27 hours (1-3.32). The mean serum creatinine at discharge was 241.87 MUmol/L
      (115.18-1063.2), at 6 months was 117.20 MUmol/l (95.6-139.9), at 12 months was
      104.55 MUmol/L (62.02-132.9), and at 24 months was 104.55 MUmol/L (62.02-132.9).
      The mean cyclosporine through level (C0) at 6 months was 137.57 ng/mL (70-366),
      at 12 months was 117.33 ng/mL (62-197), and at 24 months was 78 ng/mL. The mean
      cyclosporine 2-hour post-administration concentration levels (C2) at 6 months was
      764.9 ng/mL (430-1421), at 12 months was 937.17 ng/mL (483-1292), and at 24
      months was 690.66 ng/mL (488-853). Main complications were sepsis, adenovirus
      hemorrhagic cystitis, new-onset diabetes after transplantation, delayed graft
      function, polycythemia, and cytomegalovirus infection. No clinical rejection was
      diagnosed over the 2-year period. Patient and graft survival was 100% at a mean
      post-transplantation time of approximately 16.6 months.

PMID- 26293017
TI  - First Look: One Year Since Inception of Regional Share 35 Policy.
AB  - BACKGROUND: More than 10,000 patients are awaiting liver transplantation, and
      more than 1300 die waiting yearly. The Share 35 policy was implanted 1 year ago
      with expectations to decrease waitlist mortality. The purpose of our study was to
      look at waitlist outcomes and organ usage. METHODS: We compared data from the
      United Network of Organ Sharing before and after the initiation of Share 35,
      looking at waitlist mortality, organs shared with Model for End-Stage Liver
      Disease (MELD) score >= 35, organ discards, travel distance, cold ischemia time,
      MELD score at transplantation, donor characteristics, and waitlist times. The
      chi(2) test was used to compare the data from two time periods. RESULTS:
      Comparing the 1-year periods, we found no change in waitlist mortality rate;
      transplants in MELD score >= 35 increased from 19% to 27% and decreased in MELD
      score 15 to 34 from 74% to 67%; high-risk donors increased from 13% to 17%; and a
      40% decrease in time on the waitlist before removal because of death from 58 to
      35 days. CONCLUSIONS: One year since Share 35, there has been no change in
      waitlist mortality rate. Unfortunately, it will take several years to know the
      impact of Share 35 on changes in patient life-years saved.

PMID- 26293018
TI  - Urgency or Outcome as Guiding Principle for the Allocation of Deceased Donor
      Livers: A Questionnaire Survey Among Outpatients of a University Medical
      Department in Germany.
AB  - INTRODUCTION: The sickest-first principle has been pursued in the allocation of
      donor livers for transplantation with the introduction of algorithms based on the
      model of end-stage liver disease (MELD) score. In Germany outcomes of liver
      transplantation appear to be negatively influenced by the transplantation of
      patients with very high MELD scores and the use of donor organs with lower
      quality. Therefore, some have claimed, allocation should be based more on outcome
      oriented criteria. METHODS: A survey with binary questions (yes/no) regarding the
      appreciation of values concerning the allocation of donor livers was performed
      among general medical outpatients of a university hospital. End-stage liver
      disease patients were excluded. Two hundred four returned forms were analyzed.
      Percentages of valid answers are given. RESULTS: In this study, 88%, 73%, and 41%
      of subjects answered they would be willing to undergo transplantation with an
      estimated outcome of 20%, 50%, and 80% 1-year mortality rate, respectively, for
      themselves. Choosing a possible recipient between 2 case examples, 68% of valid
      answers voted for the case with higher age and urgency and lower long-term
      survival. Seventy percent said urgency was more important than long-term outcome
      as a criterion for organ allocation. Under the assumption that urgency-based
      allocation would decrease average long-term survival of liver transplantation,
      58% refused to deny even the sickest patients transplantation. Seventy-eight
      percent said that patients likely to achieve 50% long-term survival should not be
      denied liver transplantation. CONCLUSION: In our study a majority of subjects
      prioritize urgency and granting a chance to avert imminent death over long-term
      survival per procedure. Equitable distribution of chances for survival may be
      estimated more than outcome maximization in terms of aggregate life-years gained.

PMID- 26293019
TI  - Is It Useful to Measure Efficiency Indices of a Deceased-Donor Kidney Transplant
      Program in One Intensive Care Unit?
AB  - BACKGROUND: Before 2010, donor detection rate and donor conversion rate at our
      tertiary level care institution were low. To assess the effectiveness of the
      implemented organizational changes, an analysis of organizational indicators with
      the use of the DOPKI (Improving the Knowledge and Practices in Organ Donation)
      project was conducted. METHODS: Three groups of DOPKI indicators were used:
      indicators of the potential for deceased organ donation, indicators on areas for
      improvement in the deceased donation process, and indicators of program
      effectiveness. We compared the 3-year period before instituting organizational
      measures with the 3-year period after the changes. RESULTS: Significant
      differences in almost all DOPKI indicators were found. Most importantly, the
      number of actual donors has increased significantly, pointing to the
      effectiveness of the organizational measures that we put in place in 2010. In
      addition, the study highlights the value of the use of DOPKI indicators in one
      intensive care unit to improve the transplant program on a hospital level.
      CONCLUSIONS: We conclude by arguing that despite the lack of a uniform national
      database, DOPKI indicators could still be useful for improving the quality of
      donor programs.

PMID- 26293020
TI  - Retrospective Study of the Hungarian National Transplant Team's Cardiorespiratory
      Capacity.
AB  - The low availability of donor organs requires long-term successful
      transplantation as an accepted therapy for patients with end-stage renal and
      liver diseases. The health benefits of regular physical activity are well known
      among healthy individuals as well as patients under rehabilitation programs. Our
      aim was to describe the cardiorespiratory capacity of the Hungarian National
      Transplant Team. Twenty-five kidney (n = 21) or liver (n = 4) transplant athletes
      participated in this study. Maximal cardiorespiratory capacity (VO2max) was
      measured on a treadmill with the use of gas analysis. After a resting pulmonary
      function test, subjects completed a vita maxima test until exhaustion. Aerobic
      capacity of transplant athletes was higher than the age- and sex-predicted
      cardiorespiratory fitness (VO2max, 109.9 +/- 21.7% of the predicted values; P =
      .0101). Resting respiratory function indicators exceeded 80% of predicted age-
      and sex-matched normal values. There were positive correlations between VO2max
      and workload (r(2) = 0.40; P = .0463), metabolic equivalent (r(2) = 0.72; P <
      .0001), and oxygen pulse (r(2) = 0.30; P = .0039). However, age showed negative
      correlation with VO2max (r(2) = 0.32; P = .0031), and there was no significant
      correlation between graft age and maximal oxygen consumption (r(2) = 0.15; P =
      .4561). Although the small amount of participants can not represent the general
      kidney and liver transplant population, the excellent cardiorespiratory
      performance suggests that a normal level of physical capacity is available after
      transplantation and can be even higher with regular physical activity. This
      favorable physiologic background leads to a state that provides proper graft
      oxygenization, which is an important factor in long-term graft survival.

PMID- 26293021
TI  - Wedge Versus Core Biopsy at Time Zero: Which Provides Better Predictive Value for
      Delayed Graft Function With the Remuzzi Histological Scoring System?
AB  - BACKGROUND: Histopathological features on time-zero renal biopsies correlate with
      graft outcome after renal transplantation. With increasing numbers of marginal
      donors, assessment of pre-implantation graft quality is essential. The
      clinician's choice of wedge or core biopsy is performed without evidence of
      efficacy or safety. This study aims to compare the information derived from wedge
      biopsy versus core biopsy. METHODS: Prospective evaluation of 37 wedge biopsies
      and 30 core biopsies was performed. Histopathological data were collected on
      number of glomeruli and arterioles observed, and Remuzzi scoring for
      glomerulosclerosis, tubular atrophy, interstitial fibrosis, and arteriolar
      narrowing was performed. Clinical data on delayed graft function (DGF) were also
      collated. Sensitivity, specificity, and positive and negative predictive values
      for DGF were compared. RESULTS: Patient demographics between the two cohorts were
      comparable. No complications of biopsies occurred; 81% of wedge biopsies versus
      50% of core biopsies had >10 glomeruli (P = .01), whereas 32% of wedge biopsies
      and 57% of core biopsies had >2 arterioles (P = .02). Wedge biopsies were more
      likely to identify pathology with more glomerulosclerosis, tubular atrophy (P <
      .01), and interstitial fibrosis (P < .01). There was a non-significant trend
      toward high Remuzzi scores in wedge biopsy (22% versus 7% with Remuzzi >= 4; P =
      .12). The sensitivity and positive predictive value of Remuzzi >= 4 for
      predicting DGF was better on wedge biopsy (45.5% versus 0%; P < .01 and 62.5%
      versus 0%; P < .01, respectively). CONCLUSIONS: Wedge biopsies were safe and
      superior to core biopsies for identifying clinically significant
      histopathological findings on pre-implantation renal biopsy. We believe that the
      wedge biopsy is the method of choice for time-zero biopsies.

PMID- 26293022
TI  - Early Sirolimus Conversion as Rescue Therapy in Kidneys With Prolonged Delayed
      Graft Function in Deceased Donor Renal Transplant.
AB  - BACKGROUND: Increasing rate of delayed graft function (DGF) is seen with the use
      of Donation after circulatory death (DCD) and extended criteria donor (ECD)
      kidneys. Use of calcineurin inhibitors (CNIs) may add to insult by causing acute
      and chronic nephrotoxicity ultimately leading to primary non-function (PNF). We
      report our experience of early sirolimus (SRL) conversion in such cases in an
      attempt to salvage graft function. METHODS: Retrospective study to analyze the
      impact of early conversion of SRL in patients with prolonged DGF. Two groups were
      identified: a study (SRL) group with 14 patients and a historic control (CNI)
      group with 28 patients case-matched based on donor and recipient characteristics.
      RESULTS: SRL group included 8 ECD donors with mean DGF duration of 42.3 +/- 38.3
      days and were converted to SRL 46.6 +/- 20.6 days post-transplantation. CNI group
      had DGF duration of 26.5 +/- 9.9 days (P = .03). Mean recipient eGFR (mL/min per
      1.73 m(2)) was 12.2 +/- 4.3 pre-SRL and 26.0 +/- 11.5, 34.1 +/- 17.3 and 28.6 +/-
      14.3 at 3, 12 and 24 months post-SRL conversion respectively. Seven patients
      achieved sustained good graft function (mean Cr at 1 year of 140 MUmol/L). The
      mean eGFR of the case-matched control group was 31.7 +/- 11.7, 36.3 +/- 14.1, and
      34.9 +/- 13.9 over the same time period (P = .104, .540, and .217). CONCLUSION:
      Conversion to SRL in patients with prolonged DGF may help salvage renal graft
      function and achieve long-term graft survival in some cases where conventional
      treatment has failed. We suggest a prospective study of this targeted group to
      validate such benefit.

PMID- 26293023
TI  - Influence of Hydroxyethyl Starch on Renal Function After Orthotopic Liver
      Transplantation.
AB  - BACKGROUND: Postoperative renal impairment (RI) is one of the most common
      complications in orthotopic liver transplantation (OLT), and it occurs in 17% to
      95% of the patients who undergo the surgery. METHODS: We reviewed 394 consecutive
      patients who underwent OLT. On the basis of the preoperative renal function level
      (presence of renal failure (RF): SCr >1.5 mg/dL before OLT), the patients were
      divided into an RF group and a non-RF group. In each group, the patients were
      subdivided into 4 subgroups according to the type and dosage of the intra
      operative use of HES (hydroxyethyl starch). The changing tendency of the SCr
      (serum creatinine) of each group and the ratio of the change in the SCr within
      the first postoperative week were compared. RESULTS: In total, 139 of 394
      patients (35%) had RI within the first week after OLT (RI group); 104 patients
      (75%) in the RI group and 181 patients (71%) in the non-RI group required HES
      transfusions. The multivariate logistic regression analysis identified old age, a
      low pre-operative platelet level, and massive red blood cell transfusions as risk
      factors for the postoperative development of RI. The changing tendency of the SCr
      and the ratio of change in the SCr among the different HES subgroups showed no
      significant difference in the RF group or in the non-RF group. CONCLUSIONS:
      Perioperative use of HES 200/0.5 or HES 130/0.4 has no significant effect on
      renal function in the first postoperative week in patients undergoing OLT.

PMID- 26293024
TI  - Osthole Preconditioning Protects Rats Against Renal Ischemia-Reperfusion Injury.
AB  - BACKGROUND: Renal ischemia-reperfusion (I/R) injury is a major cause of acute
      kidney injury. The pathogenetic mechanisms of renal I/R injury involve
      inflammation, oxidative stress, and apoptosis. Osthole, a natural coumarin
      derivative, has potential anti-inflammatory effects. This study investigated the
      effect of osthole on renal I/R injury and its potential mechanism. METHODS: We
      induced renal I/R injury by clamping the left renal artery for 45 min followed by
      reperfusion, along with a contralateral nephrectomy. We randomly assigned 30 rats
      to 3 groups (n = 10): sham-operated, vehicle-treated I/R, and osthole-treated
      I/R. We treated rats intra-peritoneally with osthole (40 mg/kg) or vehicle (40
      mg/kg) 45 min before renal ischemia. We harvested serum and kidneys at 24 h after
      reperfusion. Renal function and histological changes were assessed. The
      expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8), and
      interleukin-6 (IL-6) in renal tissue and serum were examined by means of RT-PCR
      and ELISA, respectively. The expression of p-p85, p85, p-Akt, Akt, p-p65, and p65
      were measured by means of Western blotting. RESULTS: Osthole pre-treatment
      significantly attenuated renal dysfunction, renal histological changes, NF-kappaB
      activation, and the expression of TNF-alpha, IL-8, and IL-6 induced by I/R
      injury, but the activation of PI3K/Akt signaling was further increased.
      CONCLUSIONS: Osthole pre-treatment protects rats against renal I/R injury by
      suppressing NF-kappaB activation, which is involved in PI3K/Akt signaling
      activation. Thus, osthole may be a novel practical strategy to prevent renal I/R
      injury.

PMID- 26293025
TI  - Transduced Heme Oxygenase-1 Fusion Protein Reduces Renal Ischemia/Reperfusion
      Injury Through Its Antioxidant and Antiapoptotic Roles in Rats.
AB  - INTRODUCTION: Heme oxygenase-1 (HO-1) has a protective role against
      ischemia/reperfusion (I/R) injury. METHODS: We produced an HO-1 fusion protein
      mediated by cell penetrated peptide PEP-1, also known as PEP-1-HO-1 fusion
      protein, and investigated its role in renal I/R injury in rats. Male Sprague
      Dawley rats were subjected to 45 minutes of ischemia by occluding the bilateral
      renal arteries and 6 hours of reperfusion to prepare the model of renal I/R.
      Animals were randomized to receive PEP-1-HO-1 fusion protein or equal volume of
      physiologic saline 30 minutes before ischemia. RESULTS: Administration of PEP-1
      HO-1 fusion protein resulted in a significant increase in HO-1 expression. His
      probe expression (1 part of the PEP-1-HO-1 fusion protein) was only observed in
      PEP-1-HO-1-treated animals. I/R caused renal dysfunction and increases in
      malondialdehyde level and cell apoptosis, and decreased superoxide dismutase
      activity. Treatment of PEP-1-HO-1 fusion protein reversed these changes.
      Furthermore, administration of PEP-1-HO-1 inhibited the I/R-induced increase in
      nuclear factor-kappaB activation. CONCLUSIONS: These findings suggest that
      transduction of PEP-1-HO-1 attenuates renal I/R injury in rats, which might be
      partly attributable to its antioxidant and antiapoptotic effects.

PMID- 26293026
TI  - Effects of Allopurinol and Apocynin on Renal Ischemia-Reperfusion Injury in Rats.
AB  - BACKGROUND: This study evaluated the effects of allopurinol (ALP), a xanthine
      oxidase inhibitor, and apocynin (APC), a NADPH oxidase inhibitor, administered
      alone or together, on kidney damage caused by renal ischemia-reperfusion (IR) in
      rats. METHODS: Thirty rats were randomly assigned to 5 groups. Group 1 was a sham
      group. Group 2 was the renal IR control group (30-min ischemia followed by 24-h
      reperfusion). In groups 3 and 4, ALP or APC, respectively, was administered 1 h
      before the ischemia. In group 5, ALP and APC were co-administered. Blood urea
      nitrogen (BUN) and serum creatinine (Cr), renal tissue malondialdehyde (MDA) and
      superoxide dismutase (SOD), and histological changes were evaluated. RESULTS: A
      significant increase in BUN and Cr level, and histological damage was seen in the
      IR control group, indicating renal injury. Elevated MDA and decreased SOD levels
      in the IR control group demonstrated that renal damage occurred through oxidative
      stress. Pretreatment with ALP or APC alone or together prevented IR-induced renal
      damage. However, there was no significant difference between treatment with a
      single drug and co-administration of ALP and APC. CONCLUSIONS: The use of ALP
      and/or APC before ischemia may be beneficial to ameliorate renal IR injury.

PMID- 26293027
TI  - Pretreatment With Erythropoietin Attenuates Intestinal Ischemia Reperfusion
      Injury by Further Promoting PI3K/Akt Signaling Activation.
AB  - BACKGROUND: Erythropoietin (EPO) has been shown to be beneficial in resolution of
      acute inflammation and intestinal ischemia/reperfusion (IR) injury is featured by
      the excessive immune response. The current research is designed to evaluate the
      effect and potential mechanisms of EPO on the intestinal IR injury. Therefore,
      the effect of EPO on intestinal IR injury was examined by the change of
      intestinal histology; the expression of pro-inflammatory cytokines tumor necrosis
      factor alpha (TNF-alpha), interleukin 1beta (IL-1beta), and interferon gamma (IFN
      gamma); and the protein levels of EPOR, p-EPOR, p85, p-p85, Akt, p-Akt,
      IkappaBeta-alpha, p-p65, and p65. MATERIALS AND METHODS: Thirty male Sprague
      Dawley rats were randomly divided into three groups: sham group (sham), IR-saline
      group (IRI), and the IR-EPO group (EPO). Rats were treated with EPO (5000 U/kg) 1
      hour before IR induction. A rat model of IR injury was established by ligating
      the superior mesenteric artery for 30 minutes, followed by reperfusion for 1
      hour. Intestinal histology, pro-inflammatory cytokines, and mediators were
      assessed. The effect of EPO on PI3K/Akt/NF-kappaB signaling and EPOR were also
      measured. RESULTS: EPO significantly decreased the pathologic changes of
      intestinal and reduced the elevation of pro-inflammatory cytokines TNF-alpha, IL
      1beta, and IFN-gamma in intestinal and serum caused by IR which was associated
      with suppressing NF-kappaB activation by further promoting activation of PI3K/Akt
      signaling. CONCLUSIONS: EPO ameliorated the acute intestinal injury caused by IR,
      which was associated with further activating PI3K/Akt signaling to suppress NF
      kappaBeta-mediating inflammation. Our findings suggest that EPO could be useful
      for preventing IR-induced intestinal injury.

PMID- 26293028
TI  - Rapamycin Attenuates Mouse Liver Ischemia and Reperfusion Injury by Inhibiting
      Endoplasmic Reticulum Stress.
AB  - The roles of endoplasmic reticulum (ER) stress in liver ischemia and reperfusion
      injury (IRI) have been well recognized. However, the impact of rapamycin (Rapa),
      a broadly used immunosuppressive agent in human liver transplantation, on ER
      stress during IRI remains unclear. This study was designed to investigate the
      roles of Rapa in the regulation of ER stress in vivo and in vitro. In a mouse
      liver partial warm ischemia and reperfusion mode, we demonstrated that Rapa
      markedly protected livers from IRI, as evidenced by serum alanine
      aminotransferase (sALT) levels and liver histology. Then we also confirmed the
      protection of Rapa from thapsigargin (Tg)-induced cell death in primary
      hepatocytes. Both in vivo and in vitro experiments showed that the ER stress
      markers were markedly up-regulated by IRI and Tg treatment, whereas they were
      down-regulated by Rapa pretreatment, as monitored by Western blot at the protein
      levels and by quantitative reverse transcription polymerase chain reaction (RT
      PCR) at the messenger RNA (mRNA) levels. In addition, it was also revealed that
      Rapa was able to remarkably inhibit the mammalian target of rapamycin (mTOR)
      pathway and enhance autophagy both in IR-stressed livers and Tg-treated primary
      hepatocytes. Thus, these results suggest that Rapa protects livers from IRI
      through inhibiting the ER stress pathway.

PMID- 26293029
TI  - 5-HT Receptor Antagonism Attenuates the Ischemia-Reperfusion Injury After Rabbit
      Lung Preservation.
AB  - The success of lung transplantation is threatened by the appearance of ischemia
      reperfusion injury, which is characterized by increased vascular permeability. 5
      Hydroxytryptamine (5-HT; serotonin) is known to produce microvascular leakage in
      the systemic circulation, but its possible role in ischemia-reperfusion injury
      after lung preservation has not been reported. In this work we measured the
      release of 5-HT during a 24-hour rabbit lung preservation, and the effect of
      methiothepin (antagonist of the majority of 5-HT receptors) and SB204741
      (antagonist of 5-HT2B/2C receptors) on the modified capillary filtration
      coefficient (mKf,c) was evaluated at the end of this period. Our results showed
      that the highest release rate of 5-HT occurred during the first 15 minutes after
      the lung harvesting and progressively decreased in the following time intervals.
      The baseline mKf,c greatly increased after 24 hours of lung preservation, and
      this increment was partially reduced by methiothepin and even more by SB204741.
      We concluded that 5-HT may play an important role in the ischemia-reperfusion
      process after lung preservation. 

PMID- 26293030
TI  - Carnosol Is a Potent Lung Protective Agent: Experimental Study on Mice.
AB  - INTRODUCTION: Oxidative stress has been implicated in various disease states and
      ischemia/reperfusion injury is a direct consequence of oxidative stress in lung
      transplantation. Because the success rate of organ transplantation in which
      ischemia/reperfusion is inevitable is highly influenced by oxidative stress,
      development of strategies to control oxidative stress would be beneficial. Here
      we identified natural compounds to reduce oxidative stresses in isolated mouse
      lungs. METHODS: We screened compounds associated with antioxidative stress in 200
      plant extracts by monitoring the activities of nuclear factor erythroid 2-related
      factor 2 (NRF2). Compounds found to ameliorate antioxidative stress were enriched
      and mice were administered the extract orally every day for 1 week. Then, the
      lungs were isolated and cultured in the culture medium at 37  degrees C. Lung
      damage was monitored by lactate dehydrogenase (LDH) released in the culture
      medium. Arterial (left ventricle) blood gas levels were also monitored after
      hilar clamping. RESULTS: We found that Callicarpa longissima extract was rich in
      NRF2 activators. The responsible compounds were carnosic acid and its oxidative
      product, carnosol. Carnosol induced heme-oxygenase 1 (HO-1) expression, which is
      downstream of NRF2, more efficiently than carnosic acid. CONCLUSIONS: Lungs from
      mice treated with C longissima extract were less damaged than those from control
      mice and accompanied by HO-1 induction. These results suggest that carnosol is a
      candidate compound to increase the success rate of lung transplantation.

PMID- 26293031
TI  - Relationship of Changes in Cystatin-C With Serum Creatinine and Estimated
      Glomerular Filtration Rate in Kidney Transplantation.
AB  - BACKGROUND: Serum creatinine (S-Cr) is the most commonly used marker for the
      assessment of renal function in kidney transplantation (KTx). Cystatin-C (Cys-C)
      has been proposed as an alternative marker of renal function for the estimated
      glomerular filtration rate (eGFR), which seems to be more accurate than S-Cr. The
      aim of this study was to investigate the relationship between changes in S-Cr,
      Cys-C, and eGFR measurements in KT patients during the early post-transplantation
      (post-Tx) period. METHODS: Fifty consecutive patients, aged 15 to 70 years, were
      subjected to KT. Blood samples were collected at stable time-points on pre-Tx and
      post-Tx days 2, 6, and 14 and in the third month. Cys-C and S-Cr levels were
      measured, and GFR was estimated at all time-points using the Cockcroft-Gault and
      Le Bricon equations. RESULTS: S-Cr and Cys-C levels decreased significantly post
      Tx in all time-point determinations compared with pre-Tx levels. Both markers
      showed a parallel decrease, reaching normal levels in the third month. Estimated
      GFR post-Tx by S-Cr and Cys-C exhibited a parallel progressive increase without
      significant difference between the calculations. Correlation between S-Cr and Cys
      C in all time-point determinations was positive and of high significance using
      Pearson's correlation (r = 0.969, P < .01; r = 0.951, P < .01; r = 0.969, P <
      .01; r = 0.701, P < .01). Also, the correlation between the eGFR by Cys-C and S
      Cr was positive and of high significance in all post-Tx calculations (r = 0.896,
      P < .01; r = 0.935, P < .01; r = 0.929, P < .01; r = 0.861, P < .01). Ten
      recipients had acute rejection and were treated successfully with antirejection
      therapy. Their S-Cr, cys-C, and eGFR results were analyzed separately and showed
      a significant difference from no-rejection patients, with Cys-C being more
      sensitive to earlier eGFR changes. CONCLUSION: Cystatin-C is an alternative and
      accurate marker of renal function in KT patients showing similar diagnostic
      characteristics to S-Cr. However, Cys-C appears superior to S-Cr in reflecting
      early GFR temporary changes, which is critical for the early detection of acute
      rejection.

PMID- 26293032
TI  - Molecular Profile of Mitochondrial Dysfunction in Kidney Transplant Biopsies Is
      Associated With Poor Allograft Outcome.
AB  - BACKGROUND: In kidney transplantation (KT), progression of chronic histological
      damage with subclinical inflammation is associated with poor long-term allograft
      survival. The role of nonimmunological pathways in chronic allograft injury has
      not been fully assessed. METHODS: We analyzed a public microarray dataset that
      used 1-year protocol kidney transplant biopsy specimens to investigate whether
      nonimmunological genes and pathways might influence long-term allograft outcome.
      The selected microarray dataset included 3 patient/sample groups based on their
      histological findings: normal histology (n = 25), interstitial fibrosis alone (IF
      alone, n = 24), and interstitial fibrosis with inflammation (IF+i, n = 16). The
      IF+i group had lower death-censored graft survival and renal function in patients
      with a mean follow-up of 4 years. We performed statistical analysis comparing
      gene expression patterns in the 3 group samples. RESULTS: Gene cluster enrichment
      and group-specific expression patterns demonstrated a divergent pattern between
      mitochondrial and immune response genes, with downregulation of mitochondrial
      genes in the IF+i group. Gene ontological analysis of the downregulated
      mitochondrial genes identified generation of precursor metabolite and energy, and
      response to oxidative stress as the most significant biological processes. The
      transcription regulation pathway analysis of downregulated gene cluster
      demonstrated transcription factors involved in mitochondrial biogenesis.
      CONCLUSIONS: The molecular signature of mitochondrial dysfunction reflects
      mitochondrial energetic insufficiency, and inadequate antioxidant response
      involved in mitochondria biogenesis pathways is associated with IF+i and worse
      long-term allograft survival. Thus, mitochondria function impairment appears to
      be an important nonimmune factor involved in chronic allograft injury.

PMID- 26293034
TI  - Predictive Role of Neutrophil Gelatinase-Associated Lipocaline in Donor-Specific
      Antibody-Positive and Donor-Specific Antibody-Negative Renal Transplant Patients.
AB  - BACKGROUND: Renal transplantation is the best choice for the treatment of
      dialysis patients with end-stage renal failure because it provides better quality
      of life and more life time. However, despite successful surgical techniques,
      immunological issues in kidney transplantation are not completely resolved. Thus,
      after transplantation, patients must be followed up closely. Although patient
      follow-up with the use of creatinine and renal biopsy are common, it is thought
      that biopsy is too invasive and that creatinine is unreliable. Hence, new
      parameters that correlate with the patient's immunological condition are needed
      in clinical monitoring. METHODS: One of the biomarkers that has been studied
      recently is neutrophil gelatinase-associated lipocalin (NGAL). Its diagnostic
      value in cases of acute renal failure, delayed graft function, and IgA
      nephropathy is widely investigated. However, data are insufficient as to whether
      NGAL can be used for follow-up in the chronic process after renal
      transplantation. We aimed to investigate the predictive value of NGAL in terms of
      rejection in donor-specific antibody (DSA)-positive and DSA-negative renal
      transplant patients. Ninety patients were included. RESULTS: We found that
      rejection rates were higher in patients whose NGAL values were >= 50 and DSA
      positive. Delayed graft function was seen more frequently in patients whose NGAL
      values were >= 50. CONCLUSIONS: An increase in NGAL level does not always
      indicate renal injury because NGAL is also an acute-phase reactant. NGAL cannot
      be used alone to diagnose rejection, but, if NGAL level is high, it is necessary
      to study DSA, and sub-clinical rejection must be researched.

PMID- 26293033
TI  - Serum MicroRNA-99a Helps Detect Acute Rejection in Renal Transplantation.
AB  - BACKGROUND: MicroRNAs (miRNAs) are short, single-stranded, non-coding RNAs, and
      they are becoming increasingly known as potential biomarkers for a variety of
      pathologies. However, the significance of circulating miRNAs in renal
      transplantation patients needs further studies. MATERIALS AND METHODS: An miRNA
      array was used to profile the serum miRNAs of stable transplantation patients and
      transplantation patients with acute rejection (AR). We performed quantitative
      real-time polymerase chain reaction with the serum samples from 12 patients with
      AR, 11 control transplantation patients without rejection, and 15 transplantation
      patients with delayed graft function (DGF) for validation. Receiver operator
      characteristic analysis was used to assess the diagnostic capacity of serum
      miRNA. RESULTS: The miR-99a, miR-100, miR-151a, let-7a, let-7c, and let-7f were
      deregulated in the serum of the patients with AR. In the validation set, only miR
      99a and miR-100 were upregulated in the AR group. We further evaluated the
      expression levels of miR-99a and miR-100 in the DGF group. Only miR-99a was
      observed with the potent diagnostic value in discriminating AR patients from
      stable patients (area under the curve [AUC] = 0.750, 95% confidence interval [CI]
      = 0.529-0.971, P = .042) and DGF patients (AUC = 0.811, 95% CI = 0.600-1.000, P =
      .006). CONCLUSION: Serum miR-99a may serve as a biomarker of AR in renal
      transplantation patients. Further studies are required to confirm the results.

PMID- 26293035
TI  - Measurement of Internal and External Pressure of Transplanted Kidney: An
      Underestimated Method of Diagnosis for Renal Grafts.
AB  - Hardness, or tensity (tonus), of transplanted kidney can change in the course of
      various pathologic conditions. Manual examination (with palpation), which is most
      frequently used to evaluate this transplanted organ, is not objective. First
      attempts of objective evaluation were described in the medical literature in the
      1980s. They consisted of evaluation of intrarenal pressure by puncturing the
      kidney, connecting an intravenous drip line, and measuring the pressure in
      centimeters of water column. Examination of a group of subjects revealed
      significant differences in mean measurements, especially in patients with acute
      rejection process compared with the control group. However, use of this method
      was not continued, owing to its invasiveness. Our own diagnostic method,
      described here, is measurement of external kidney pressure (tonus). Two types of
      devices (tonometers) are described, as well as a project of a future tonometer
      functioning on the basis of electronically measured differences in values of
      forces used above the graft and above the symmetric part of the abdomen causing
      identical deflection of abdominal wall. Thirty-two patients (including control
      group) were examined with the use of this method. Statistically significant
      differences were revealed between patients with acute graft rejection and chronic
      graft nephropathy compared with the control group. The method described here can
      be a valuable supplement to other currently used noninvasive means of renal graft
      evaluation, including ultrasonography, Doppler, and elastographic examinations. 

PMID- 26293036
TI  - Impact of Renal Transplantation and Nephrectomy on Urinary Soluble Klotho
      Protein.
AB  - BACKGROUND: Klotho is a single-pass transmembrane protein predominantly expressed
      in the kidneys. The soluble form of klotho has been shown to participate in
      various pathophysiological activities. However, information regarding the
      kinetics of soluble klotho remains limited. We herein assessed serial changes in
      the amounts of 24-hour urinary excreted soluble klotho among renal transplant
      recipients and concomitant living donors before and after transplantation.
      METHODS: A total of 15 recipients and donors were included in the current study,
      and the amounts of urinary soluble klotho were quantified using a sandwich enzyme
      linked immunosorbent assay. RESULTS: Urine samples were available in 6 of the 15
      recipients prior to the procedure. The amounts of urinary klotho in these 6
      recipients and overall living donors at the baseline were 58.6 ng/day (IR: 29.3
      142) and 698.8 ng/day (IR: 62.3-1619.5), respectively. Those in the recipients on
      postoperative day 2 (median 522.3 ng/day; IR 337.1-1168.5, P < .05) and day 5
      (median 723.2 ng/day; IR 254.7-1238.6, P < .05) were significantly higher than
      the baseline values. Among the living donors, only a transient increase was
      observed in the amounts of urinary klotho on postoperative day 2. CONCLUSION: The
      current data regarding the urinary soluble klotho in recipients support the
      hypothesis that the kidney is a major source of urinary soluble klotho among the
      numerous components of the urinary tract. In living donors, the complex nature of
      events associated with acute reductions in the renal mass may modulate the
      release of soluble klotho from the kidneys into the urine.

PMID- 26293037
TI  - Evolution of Renal Transplant Practice Over the Past Decade: A U.K. Center
      Experience.
AB  - OBJECTIVE: As renal transplantation continues to evolve, there appears to be a
      change in both donor and recipient populations. Traditional markers of high-risk
      donor (e.g. donation after cardiac death [DCD]/expanded criteria donor [ECD]) and
      recipient (e.g. obese, highly sensitized) operations appear to be more common
      without any noticeable worsening of patient outcome. The present study aimed to
      compare outcome and define the change in donor and recipient populations for
      cadaveric transplants over a 10-year period at a large U.K. center. METHODS:
      Single-center analysis of all adult patients undergoing cadaveric renal
      transplantation between January 2004 and January 2014 (n = 754). Transplants were
      divided into 3 groups (early, middle, and late) depending on the era, with donor,
      recipient and outcomes compared. RESULTS: There were considerable changes in both
      donor and recipient factors between the 3 eras, with a greater proportion of high
      risk operations performed, as reflected by significant increases in Donor Risk
      Index (median: 1.11-1.16, P = .022), and the proportions of ECD (22.2%-33.9%, P =
      .003) and DCD kidneys (10.8%-19.4% P = .011). However, 1-year graft survival was
      comparable between the eras, with a decrease in the average 1-year serum
      creatinine between the early and late cohort (median: 161 MUmol/L vs 132 MUmol/L,
      P < .001). There was no significant increase in body mass index (BMI) in either
      the donor or recipient population across the eras. CONCLUSION: Improvement in
      transplant outcome continues despite a greater proportion of transplants
      previously considered as high risk being performed. This is likely to reflect a
      considerable improvement in pre- and postoperative management. BMI remains a
      major continuing block to transplantation.

PMID- 26293038
TI  - Evolution of Renal Function in Renal Allograft Recipients Under Various
      Everolimus-Based Immunosuppressive Regimens.
AB  - BACKGROUND: Long-term allograft survival is a major challenge in kidney
      transplantation. This study sought to estimate the evolution of renal function in
      patients receiving different immunosuppressive regimens based on everolimus
      (EVR). METHODS: Ninety-nine renal allograft recipients were included in a 12
      month open-label, noninterventional, prospective, single-center study. Patients
      were divided into 2 groups, de novo and late conversion to EVR. RESULTS: Group A
      included 40 patients under calcineurin inhibitor (CNI) plus EVR. Median time
      posttransplantation was 33.06 months (interquartile range 18.25 to 42.85). Mean
      estimated glomerular filtration rate (eGFR) the first month posttransplantation
      (using Modification of Diet in Renal Disease formula) was 54.89 +/- 19.08 mL/min,
      and mean proteinuria was 0.54 +/- 0.38 g/24 h. At the end of follow up, mean eGFR
      and mean proteinuria significantly improved (65.49 +/- 20.79 mL/min; P = .011 and
      0.157 +/- 0.089 g/24 h; P = .002, respectively). Group B consisted of 59
      patients; 49 of them initially received mycophenolic acid (MPA) plus CNI, and 10
      had been on azathioprine plus CNI. Initial immunosuppression was switched to MPA
      plus EVR in 49 patients, CNI plus EVR in 4 patients, and EVR in 6 patients, in a
      median time of 37 months (interquartile range 14.75 to 112.5)
      posttransplantation. Main indications for conversion were malignancies and biopsy
      proven chronic allograft injury. Mean eGFR 1 month posttransplantation and at the
      time of conversion were 50.79 +/- 17.83 mL/min and 57.39 +/- 19.17 mL/min,
      respectively (P = .014). After conversion, mean eGFR increased (66 +/- 24.89
      mL/min; P = .006). Mean proteinuria was 0.509 +/- 0.530 g/24 h the first
      posttransplantation month, and it remained stable at 0.415 +/- 0.431 g/24 h until
      study completion. Two acute rejection episodes occurred. At the end of follow-up,
      patient and death-censored graft survival were 97% and 100%, respectively.
      CONCLUSIONS: In kidney transplant recipients, EVR either de novo or after
      conversion with or without CNI is a safe and effective treatment that preserves
      renal function.

PMID- 26293039
TI  - Transplantation of Restored Kidneys From Unrelated Donors After Resection of
      Renal Cell Carcinoma: Results From 10 Patients.
AB  - PURPOSE: To relieve the chronic shortage of donor kidneys, we conducted a
      prospective kidney transplantation trial using kidneys removed from 10 unrelated
      patients (51 to 79 years of age) who had undergone nephrectomy for small renal
      cell carcinoma (1.5 to 3.9 cm) of low-to-moderate complexity based on RENAL
      (radius, exophytic/endophytic properties, nearness of tumor to the collecting
      system or sinus in millimeters, anterior/posterior location relative to polar
      lines) nephrometry (objective description helpful for operative indication and
      planning). METHODS: Donors were selected from among 15 patients who opted to
      undergo nephrectomy for small renal cell carcinoma. A total of 76 dialysis
      patients 34 to 85 years of age who agreed to undergo restored kidney
      transplantation were recruited as transplant candidates. RESULTS: In stage 1 (5
      cases), high-risk patients were selected without human leukocyte antigen testing,
      and accelerated acute rejection occurred in 4 of 5 recipients. This trial was
      subsequently extended with human leukocyte antigen testing, and an additional 5
      patients were enrolled in stage 2. Eight recipients, including 4 recipients with
      a history of renal transplantation, experienced rejection; 1 patient resumed
      dialysis 35 months after transplantation. The most recent serum creatinine levels
      ranged from 1.10 to 3.19 mg/dL in the 9 recipients with functioning grafts and
      from 0.84 to 4.68 mg/dL in the 10 donors. No tumor recurrence was noted at 32 to
      58 months after surgery in either the recipients or the donors. CONCLUSIONS:
      Restored kidney transplantation using kidneys with a small renal tumor seems
      suitable for carefully selected high-risk recipients and, in particular, elderly
      kidneys can also function well. Avoiding cancer transmission, fair recipient
      selection, close follow-up, and a well-organized tracking system warrant further
      study.

PMID- 26293040
TI  - Long-term Outcomes of ABO-Incompatible Living Donor Kidney Transplantation: A
      Comparative Analysis.
AB  - BACKGROUND: Although ABO-incompatible kidney transplantation has become more
      common due to organ shortage, few studies on long-term outcomes have been
      performed in the Korean population. METHODS: A retrospective review of medical
      records was conducted for individuals who underwent living donor kidney
      transplantation at Asan Medical Center from February 2009 to January 2012.
      RESULTS: A total of 469 patients were included; the mean age was 42.8 +/- 11.8
      years, and the median follow-up period was 45 (range, 1-65) months. ABO
      incompatible recipients (73) were compared with ABO-compatible patients (396).
      Patient survival was similar between the ABO-incompatible group (97.3% and 95.9%
      at 1 and 3 years) and the ABO-compatible group (99.0% and 98.5% at 1 and 3 years;
      P = .136). Death-censored graft survival was also comparable between groups
      (98.6% vs 99.7% at 1 year; 98.6% vs 98.7% at 3 years; P = .386). Graft function,
      acute rejection, and postoperative complications were not significantly different
      between groups. Additionally, high body mass index and multiple human leukocyte
      antigen mismatches were significant risk factors for acute rejection (OR: 1.08,
      95% CI: 1.01-1.16, P = .033; and OR: 1.20, 95% CI: 1.02-1.40, P = .025,
      respectively). CONCLUSION: ABO-incompatible kidney transplantation could be a
      safe option when ABO-compatible donors are not available.

PMID- 26293041
TI  - Dual Kidney Transplantation From Pediatric Donors to Adult Recipients.
AB  - BACKGROUND: The organ shortage is a global problem. A potential approach to
      expanding the deceased donor pool is to harvest organs from pediatric patients.
      METHODS: Seven cases of dual kidney transplantation from pediatric donors to
      adult recipients were performed between 2012 and 2014 in our center. The proximal
      end of the donor aorta (AO) was anastomosed to the right common iliac artery or
      external artery. The proximal end of the donor inferior vena cava (IVC) was
      anastomosed to the right external iliac vein. Recipients received basiliximab or
      antithymocyte globulin as induction therapy, followed by tacrolimus,
      mycophenolate mofetil, and prednisone. Prophylactic anticoagulation was not
      universal in our study. RESULTS: During the 21-month study period, both patient
      and graft survivals were 100%. No patient showed thrombotic complications.
      Complications included an acute rejection episode in 1 patient, urine leakage in
      2, and anticoagulation related hemorrhage in 1. All recipients had excellent
      graft function with normal serum creatinine ranging from 0.49 to 1.45 mg/dL and
      estimated glomerular filtration rate ranging from 56.89 to 145.27 mL/min/1.73
      m(2). CONCLUSIONS: Dual kidney transplantation from pediatric donors to adult
      recipients is a promising way to expand the donor pool. Using the proximal end of
      the AO/IVC for anastomosis brings satisfactory results.

PMID- 26293042
TI  - Assessment of the Changes in Health-related Quality of Life After Kidney
      Transplantation in a Cohort of 232 Thai Patients.
AB  - AIM: The aim of this study was to investigate QoL of these patients before and
      after KT and to determine relationships between basic factors of gender, age,
      educational background, marital status, income, and QoL of patients after
      undergoing KT. METHODS: A retrospective study to determine HQoL of 232 ESRD
      patients who received KT in a single center in Thailand. HQoL was determined by 3
      methods: WHO questionnaires, EQ5D questionnaires, and visual analog scale (VAS)
      questionnaires. Other important demographic information including gender, age,
      education, marital status, and family income were recorded. Pre- and post-KT HQoL
      was scored and compared. The Pearson method was used to calculate correlation
      statistics. RESULTS: WHO QoL is significantly improved in all domains including
      physical health, psychological health, social health, and environmental health
      after KT (P < .001). EQ5D QoL is also significantly improved after KT for the
      categories of self-mobility, self-care, pain, distress, anxiety, and depression.
      The mean score of VAS before KT was 40.98 and rose to 83.10 after KT (P < .001).
      Gender and marital status were not significantly correlated with quality of life.
      The level of education and average income of the family are positively correlated
      with increased QoL after KT (P < .01 and P < .001). However, age is negatively
      correlated with increased QoL (P < .05). CONCLUSION: Successful KT leads to a
      significant increase of HQoL as determined by 3 independent measurements. The
      improvement is shown by better physical health, psychosocial health,
      environmental health, and functional abilities of the transplant recipients. Our
      results confirm that KT should be the treatment of choice for patients with ESRD.

PMID- 26293043
TI  - Midterm Outcome of Living-Related Kidney Transplantation From Aged Donors: A
      Single-Center Experience.
AB  - BACKGROUND: Kidney transplantation (KT) is the most effective treatment of end
      stage renal disease (ESRD). Using grafts from aged donors is increasing
      worldwide. Our aim was to better understand the safety and effectiveness of aged
      living donors. METHODS: First, 482 cases with living-related kidney
      transplantation were analyzed retrospectively. The cases were divided into 2
      groups by donor age >= 55 years (aged donor group, 136 cases) and <55 years
      (young donor group, 346 cases). Then donor and recipient characteristics were
      summarized. In addition, the renal function of graft was compared between young
      donor group and aged donor group. Finally, patient and graft survivals were
      examined with the use of Kaplan-Meier analysis and compared with the use of the
      log-rank test. RESULTS: The mean donor estimated glomerular filtration rate
      (eGFR) was lower in the aged donor group compared with in the young donor group.
      After KT, the mean eGFR of the graft in the recipient was also lower in the aged
      donor group than in the young donor group. To confirm the effect of aged kidney
      grafts on renal function, we measured proteinuria. Compared with the young donor
      group, in the aged donor group incidence of proteinuria and 24-hour urinary
      protein were significantly higher. However, the incidence of delayed graft
      function was not significantly different between the 2 groups. We found that aged
      kidney grafts had no significant effect on long-term patient and graft survivals.
      CONCLUSIONS: With the current lack of organs, aged kidney grafts are an
      acceptable alternative. Use of organs from aged donors safely expands the living
      donor pool.

PMID- 26293044
TI  - Early or Late Conversion From Tac-BD to Tac-BD in Renal Transplantation: When is
      the Right Time?
AB  - BACKGROUND: Increasing numbers of renal transplant recipients are converted from
      Prograf (Astellas Pharma, Tokyo, Japan) (tacrolimus twice daily [Tac-BD]) to
      Advagraf (Astellas) (tacrolimus once daily [Tac-QD]), but the optimal time for
      conversion is as yet unclear. This study aimed to investigate the correlation
      between the time of conversion from Tac-BD to Tac-QD after renal transplant and
      the dosing requirements, tacrolimus levels, renal function, and clinical
      outcomes. METHODS: Since September 2008, 125 renal transplant patients were
      converted from Tac-BD to Tac-QD and followed up for 2 years after conversion.
      Patients were split into early (0 to 12 months) and late (>12 months) conversion
      groups. Demographics, Tac-QD dose, trough levels, graft function, and patient and
      graft outcome were prospectively collected. RESULTS: Forty-four patients (35.2%)
      were converted early (3.82 +/- 3.24 months), whereas 81 (64.8%) patients were
      converted late (77.35 +/- 53.71 months). Tac-BD dose before conversion was higher
      in the early group (8.70 +/- 6.34 vs 4.44 +/- 2.15 mg) as was the initial Tac-QD
      dose (8.66 +/- 6.20 vs 4.37 +/- 2.04 mg, P < .0001), and remained higher for 18
      months after conversion, as did the serum tacrolimus trough level levels. Renal
      function, acute rejection, and patient and graft survival were comparable between
      the groups. CONCLUSIONS: Patients can be safely converted to Tac-QD within the
      first year post-transplantation, without adverse effects on clinical outcome,
      despite the higher doses and tacrolimus levels for the first 18 months.

PMID- 26293045
TI  - Association Between Interleukin-2 -330 T/G Polymorphism and Acute Renal Graft
      Rejection: A Meta-analysis.
AB  - BACKGROUND: Interleukin-2 (IL-2) -330 T/G promoter polymorphism is involved in
      the acute rejection (AR) risk of kidney transplantation. However, results from
      published studies on the association between recipient IL-2-330 T/G polymorphism
      and AR risk are conflicting and inconclusive. METHODS: We searched Medline,
      Embase, Web of Science, and Cochrane Central Register from their inceptions
      through January 2015 for relevant studies. Data concerning publication
      information, population characteristics, and transplant information were
      extracted. Odds ratios (ORs) were calculated for the association between IL-2-330
      T/G polymorphism and AR risk. RESULTS: This meta-analysis included 8 case-control
      studies with 1,405 cases of renal transplant recipients. The pooled estimate
      showed that IL-2-330 T/G polymorphism was not associated with AR risk: TT vs
      TG+GG: OR(fixed,) 0.93; 95% confidence interval [CI], 0.72-1.21; P = .60; GG vs
      TG+TT: OR(fixed), 1.15; 95% CI, 0.76-1.72; P = .51; TG vs TT+GG: OR(fixed), 1.01;
      95% CI, 0.78-1.31; P = .91; T vs G: OR(fixed), 0.93; 95% CI, 0.77-1.13; P = .48.
      None of subgroup analyses yielded significant results in the association between
      IL-2-330 T/G polymorphism and AR risk. Meta-regression confirmed that there was
      no significant correlation between the preselected trial characteristics and our
      study results. CONCLUSIONS: This meta-analysis suggests that IL-2-330 T/G
      polymorphism may not be associated with AR risk in renal transplant recipients.

PMID- 26293046
TI  - Eculizumab for Treatment of Refractory Antibody-Mediated Rejection in Kidney
      Transplant Patients: A Single-Center Experience.
AB  - Antibody-mediated rejection (AMR) is responsible for up to 20%-30% of acute
      rejection episodes after kidney transplantation. In several cases, conventional
      therapies including plasmapheresis, intravenous immunoglobulin, and anti-CD20
      therapy can resolve AMR successfully. But in some cases the load of
      immunoglobulins that can activate complement cascade may submerge the routine
      desensitization therapy and result in the formation of membrane attack complexes.
      Eculizumab, a monoclonal antibody against C5, was reported to be an option in
      cases with severe AMR that are resistant to conventional therapy. Here, we
      present 8 cases that were resistant to conventional therapy and in which
      eculizumab was given as a salvage treatment. Given the bad prognosis for renal
      transplants displaying acute injury progressing rapidly to cortical necrosis on
      the biopsy, the prompt use of eculizumab could have the advantage of immediate
      effects by stopping cellular injury. This can provide a therapeutic window to
      allow conventional treatment modalities to be effective and prevent early graft
      loss. 

PMID- 26293047
TI  - Primary and Recurrent Focal Segmental Glomerulosclerosis Closely Link to Serum
      Soluble Urokinase-type Plasminogen Activator Receptor Levels.
AB  - BACKGROUND: Serum soluble urokinase-type plasminogen activator receptor (suPAR)
      is implicated in the pathogenesis of native and recurrent focal segmental
      glomerulosclerosis (FSGS). It is elevated in two-thirds of subjects with primary
      FSGS, but not in people with other glomerular diseases that can differentiate
      FSGS and other glomerular diseases. METHODS: We measured the serum soluble
      urokinase receptor levels and determined their association with clinical and
      pathologic data in 86 patients with primary FSGS, 5 repeat renal biopsy FSGS, and
      6 recurrent FSGS post-transplantation. Healthy controls and patients with minimal
      change disease and membranous nephropathy were used as controls. The suPAR levels
      were measured by commercial enzyme-linked immunosorbent assay kits. RESULTS:
      Patients with primary FSGS (median: 4232, interquartile range 1299-9714 pg/mL)
      had significantly higher levels of suPAR than those of patients with minimal
      change disease (median: 2784 pg/mL), membranous nephropathy (median: 3478 pg/mL),
      and healthy individuals (median: 1994 pg/mL). There was no significant difference
      in suPAR levels between the 65 patients with minimal change disease and 85
      patients with membranous nephropathy. The suPAR levels increased in the 5
      repeated renal biopsy FSGS and 6 recurrent FSGS post-transplantation.
      CONCLUSIONS: The suPAR levels were significantly but positively correlated with
      FSGS, not only primary FSGS but also recurrent FSGS post-transplantation, but
      negatively correlated with other glomerular diseases. Thus, suPAR levels can
      differentiate primary FSGS and other glomerular diseases.

PMID- 26293048
TI  - Flexible Ureterorenoscopy and Laser Lithotripsy for the Treatment of Allograft
      Kidney Lithiasis.
AB  - OBJECTIVE: To evaluate the safety and effectiveness of flexible ureterorenoscopy
      (F-URS) and laser lithotripsy for the treatment of allograft kidney lithiasis.
      PATIENTS AND METHODS: In a retrospective analysis of 897 consecutive renal
      transplantations that were performed at our center between February 2008 and
      December 2014, 6 patients were found to have allograft lithiasis. F-URS and laser
      lithotripsy were performed 6 times on 5 patients (twice for 1 patient who had
      stone recurrence after 6 months). Percutaneous nephrolithotomy was used for the
      remaining patient. Patient demographics and stone characteristics (age, sex,
      stone size, stone analysis, location, history of shockwave lithotripsy) and
      perioperative measures (duration of operation, fluoroscopic imaging, success and
      complication rates) were reviewed. In addition, the technical difficulties of
      standard F-URS procedures in transplanted kidneys were reviewed and some
      facilitative techniques were defined to increase the success rate. RESULTS: A
      total of 5 patients underwent 6 F-URS procedures and laser lithotripsy operations
      for renal graft lithiasis. The mean stone size was 9.2 mm (7.5-11 mm). The mean
      operation and fluoroscopy times were calculated as 55 minutes (40-70 minutes) and
      57.5 seconds (40-80 seconds), respectively. Treatment was successful in all
      patients and no severe complications or mortality occurred. One patient
      experienced transient hematuria and recovered within 36 hours. CONCLUSION: F-URS
      is a safe, effective, and minimally invasive treatment modality for small- and
      medium-sized stones in allograft kidney lithiasis.

PMID- 26293049
TI  - Accuracy of Inpatient International Classification of Diseases, Ninth Revision,
      Clinical Modification Coding for Cytomegalovirus After Kidney Transplantation.
AB  - BACKGROUND: International Classification of Diseases, Ninth Revision, Clinical
      Modification (ICD-9-CM) coding for cytomegalovirus (CMV) has been used as a proxy
      for active CMV infection or disease occurring in the inpatient setting in
      retrospective studies of kidney transplant recipients using large amounts of
      administrative data. However, the accuracy of inpatient CMV coding has not been
      determined. METHODS: We identified 393 kidney transplant recipients who were
      readmitted to Barnes-Jewish Hospital in St. Louis, Missouri from January 1, 2007
      to December 31, 2011 to determine the accuracy of the ICD-9-CM diagnosis code for
      CMV (078.5) in identifying active CMV infection or disease (asymptomatic viremia,
      CMV syndrome, or tissue-invasive CMV disease) in the inpatient setting, using
      microbiological, histopathologic, or ophthalmologic evidence for CMV as the gold
      standard. RESULTS: The sensitivity and positive predictive value of CMV coding in
      identifying active CMV infection or disease were 0.77 and 0.71, respectively. The
      specificity and negative predictive value were both 0.98. The sensitivity of CMV
      coding in identifying CMV syndrome or tissue-invasive CMV disease was 0.93.
      CONCLUSIONS: CMV coding had good accuracy in identifying active CMV infection or
      disease among readmitted kidney transplant recipients in our hospital. Further
      validation studies of CMV coding in other hospitals are needed to obtain more
      generalizable estimates of the accuracy of CMV coding.

PMID- 26293050
TI  - BK Virus Nephropathy in Kidney Transplantation: An Approach Proposal and Update
      on Risk Factors, Diagnosis, and Treatment.
AB  - BK virus belongs to Polyomaviridae family; it causes 95% of nephropathy cases
      related to polyomavirus, with the other 5% caused by JC virus. Nephropathy
      jeopardizes graft function, causing a premature failure of the graft in 1%-10% of
      patients with kidney transplants. Nowadays, antiviral effective treatment is
      unknown, which is why blood and urine screening of renal transplantation patients
      has become the most important recommendation to guide the decrease of
      immunosuppression, and the only proven method to decrease poor outcomes.
      Different interventions, such as cidofovir, leflunomide, fluoroquinolones, and
      intravenous immunoglobulin, have been attempted with no improvement at all. This
      review aims to summarize the most relevant features of BK virus, historical
      issues, transmission mechanisms, risk factors, and therapeutic interventions. 

PMID- 26293051
TI  - Late-Onset BK Viruria in Renal Transplant Recipients.
AB  - BACKGROUND: Most cases of BK virus (BKV) infections emerge within the 1st years
      of kidney transplantation. We aimed to determine the prevalence of late-onset BKV
      infection and whether there are any differences between risk factors in early and
      late BKV infections. METHODS: In this single-center retrospective study, we
      reviewed 300 kidney transplant recipients that were under regular follow-up and
      selected recipients with BKV infection and recorded associated risk factors,
      connection with immunosuppression, and responses to modification of treatment.
      RESULTS: BKV was detected within the 1st 5 years after transplantation in 20
      patients (6.6%, group 1) and after 5 years in 15 patients (5.0%, group 2). There
      were no significant differences between the 2 groups regarding age, sex, sex
      mismatches, donor type, BKV elimination time, serum creatinine, and estimated
      glomerular filtration rate at the times of BKV detection and last follow-up
      visit. In group 1, 2 recipients had biopsy-proven BKV-associated nephropathy
      (BKVAN), 3 recipients had BK viruria and viremia without BKVAN (biopsy proven),
      and 15 recipients (75%) had only BK viruria. In group 2, all of the patients had
      only BK viruria. In this group, on detection of BK viruria and immediate
      modification of immunosuppressive regimens prevented BK viremia. CONCLUSIONS:
      Routine screening of renal transplant recipients for BKV was indicated not only
      during the 1st 5 years, but also for the full follow-up period after
      transplantation.

PMID- 26293052
TI  - Prospective Evaluation of Rapid Antigen Tests for Diagnosis of Respiratory Viral
      Pathogens.
AB  - Acute respiratory infection is a frequently transmitted illness of concern to
      doctors and patients. Considering its airborne transmission, early diagnosis of
      such disease is particularly important. This study explored respiratory viral
      infections with influenza virus, parainfluenza virus, respiratory syncytial
      virus, human metapneumovirus, human bocavirus, coronavirus, and other early
      diagnostic substances as confirmed by literature resources. This study also used
      the corresponding monoclonal antibodies that were produced with the use of
      hybridoma technology, which were fixed on the chip after purification, for
      further serum detection. Using this method, a new technique to simultaneously
      detect 6 kinds of febrile respiratory viruses in a protein chip was developed.
      The accuracy rate of this method can be >99.65%. This product is inexpensive and
      capable of high-precision and high-throughput screening, which are prominent
      advantages. 

PMID- 26293053
TI  - WITHDRAWN: Natural Killer Cell Activating Receptor NKG2D Is Involved in the
      Immunosuppressant Effect of Mycophenolate Mofetil and Infection of Hepatitis B
      Virus.
AB  - In this study we investigated whether mycophenolate mofetil (MMF), a new
      immunosuppressant, and its metabolite mycophenolic acid (MPA) influence the
      activity of liver resident natural killer (NK) cells, resulting in increased
      susceptibility to hepatitis B virus (HBV) infection. We isolated the hepatic NK
      cells of C57BL/6 and C57BL/6JTgN (A1b1HBV) 44Bri) transgenic mice administered
      MMF in the presence or absence of interleukin (IL)-15, or incubated isolated
      hepatic NK cells in the presence or absence of MPA and used RT-PCR,
      immunolabeling to assess the expression of NK receptors Ly49A, NKG2A and NKG2D,
      and cytokine ELISA and [(3)H]-TdR-release assay to assess the activation and
      cytotoxic capacity of NK cells. After treatment of MMF in the presence or absence
      of IL-15, HBsAg titer was also measured in C57BL/6JTgN (A1b1HBV) 44Bri)
      transgenic mice. After both MPA and MMF treatments, NK cytotoxicity was reduced,
      NKG2D and Ly49A expression was down-regulated, but NKG2A was up-regulated. Down
      regulation of NKG2D could be ameliorated by IL-15, and in HBV-transgenic mice,
      MMF treatment impaired NK cell activity, but did not influence virus replication,
      whereas IL-15 treatment depressed HBsAg titer. MPA and MMF mediate down
      regulation of NKG2D in vitro and vivo, restricting the cytotoxic capacity of NK
      cells. Regulation of NKG2D may be important in the effect of immunosuppressant on
      NK cell activity and involved in HBV infection.

PMID- 26293054
TI  - Clinical Utility of Viral Load in the Management of Cytomegalovirus Infection in
      Solid Organ Transplant Patients in Kuwait.
AB  - BACKGROUND: Infection with human cytomegalovirus (CMV) in solid organ transplant
      patients remains an unresolved challenge, despite improvements in
      immunosuppressive therapy, post-transplantation care, viral prevention, and
      therapy. METHODS: We conducted quantitative real-time polymerase chain reaction
      (PCR) assays of CMV on plasma samples of 1,168 patients in Kuwait who received
      solid organ transplants from 2012 to 2014 to detect and monitor CMV DNA viral
      load. RESULTS: Of the 1,168 patients, 180 (15.4%) were positive for CMV DNA.
      Among the CMV DNA-positive patients, 119 (66.1%) remained without symptoms and 61
      (33.9%) developed CMV-related symptoms. During the follow-up period, peak viral
      loads were significantly (P < .05) higher in symptomatic patients (mean 970
      copies/mL; range, 15-625,000 copies/mL) than in asymptomatic patients (<150
      copies/mL; range, 67-2,650 copies/mL). Many symptomatic patients (n = 57) were
      successfully treated, and their viral loads declined. However, some symptomatic
      patients had irregular viral-load kinetics, with prolonged periods of symptoms
      despite CMV treatment; we excluded the possibility of drug resistance in these
      patients, because there was no evidence of clinical resistance to treatment.
      CONCLUSIONS: Quantitative real-time PCR of CMV DNA is useful in monitoring CMV
      infection and the effectiveness of CMV treatment in renal transplant recipients
      in Kuwait.

PMID- 26293055
TI  - Bacterial Infections in Renal Transplant Recipients.
AB  - BACKGROUND: Patients after kidney transplantation are highly susceptible to
      infections owing to immunosuppression as well as other risk factors--extended
      hospitalization, Foley catheterization, and double J catheter insertion among
      others. Bacterial infections, especially shortly after operation, are a major
      threat to the graft function. The aims of this study were to identify risk
      factors of bacterial infections after kidney transplantation and to determine the
      impact of those infections on the subsequent renal function. METHODS: One hundred
      twenty patients who underwent kidney transplantation in 2013 and 2014 were
      examined in our study for possible risk factors of bacterial infections and for
      possible outcome of such infections on their future condition. RESULTS: Among 120
      patients under observation, 50 (41.7%) had early infectious complications (during
      hospitalization), 41 (82%) of which were urinary tract infections (UTI). The
      second most common infectious complication was infection of the surgical wound.
      Statistically significant results were obtained only for patient's age and
      duration of hospital stay (P = .001 and P = .000004, respectively). Bacterial
      infection resulted in longer hospital stay, higher reoperation risk, and lower
      creatinine clearance in the 14 days after transplantation (P = .000004, P =
      .0142, and P = .0455, respectively). CONCLUSION: Bacterial infections influence
      mainly the short-term condition of kidney transplant recipients: extended
      hospital stay, decreased early creatinine clearance, and enhanced risk of
      reoperation. The most common risk factors, such as Foley catheterization, double
      J catheter insertion, and diabetes, were not significant in our observation.

PMID- 26293056
TI  - Successful Renal Transplantation, Bone Mineral Densitometry, and Affecting
      Factors.
AB  - BACKGROUND: Successful renal transplantation corrects many disorders of bone and
      mineral metabolism owing to the normalization of serum levels of calcium and
      phosphorus and restoration of calcitriol production. However, successful
      transplantation does not guarantee complete resolution of the pre-transplantation
      osteopathy. METHODS: This study evaluated 100 patients who underwent successful
      renal transplantation. We determined the possible risk factors for osteoporosis
      among 72 male and 28 female renal transplant patients of mean age 32.3 +/- 10.0
      years with 81% of them recipients of living-related grafts. Bone mineral
      densitometry (BMD) was performed in all patients before and >= 1 year after
      transplantation. Routine test results and demographic data were recorded.
      RESULTS: At the time of transplantation 76% of the patients had osteoporosis or
      osteopeni and only 24% of them had normal BMD in 4 regions (femur neck, lumber,
      radius, and ultradistal). After transplantation, 70% of them had osteopororosis
      or osteopeni and 30% were normal. After renal transplantation, BMD scores
      increased (P > .05) although the diagnosis of the bone disease did not change (P
      < .05). Only preexisting osteodystrophy and smoking were found to be important
      risk factors for post-transplantation osteoporosis. CONCLUSIONS: After renal
      transplantation, BMD scores increased whereas the diagnosis of bone disease did
      not change statistically. We found that medical management of
      osteopenia/osteoporosis before transplantation and smoking habit are the main
      factors to prevent post-transplantation osteoporosis. Further long-term studies
      may be more helpful for evaluating the risk factors of post-transplantation
      osteoporosis.

PMID- 26293057
TI  - Pre-Transplant Erythropoiesis-Stimulating Agent Hypo-Responsiveness and Post
      Transplant Anemia.
AB  - BACKGROUND: At the time of kidney transplantation (KT), almost all patients have
      anemia caused by low levels of endogenous erythropoietin (EPO), along with
      several other factors. After KT, anemia improves because of secretion of EPO from
      the allograft. But some recipients have persistent anemia. Whether or not
      erythropoiesis-stimulating agent (ESA) hypo-responsiveness before KT affects post
      transplant anemia (PTA) remains unknown. METHODS: Sixty-eight patients received
      KT between January 2007 and July 2012 through the Department of Urology at Kobe
      University Hospital, and 35 of these patients were enrolled. Exclusion criteria
      included age <18 years, unknown ESA dosage at transplantation, ESA start within 1
      year after transplantation, and other criteria. We evaluated post-transplant
      hemoglobin (Hb) levels from the pre-transplant ESA responsive index (ERI): pre
      transplant ESA dosage/Hb * body weight at 1 year after transplantation. RESULTS:
      The mean (+/- SD) Hb of all patients rose from 11.3 +/- 1.0 mg/dL to 12.7 +/- 1.4
      mg/dL at 1 year after transplantation (P < .01). The pre-transplant low ERI group
      (<10) showed significantly higher hemoglobin levels compared with the pre
      transplant high ERI group (>= 10; 12.9 +/- 1.14 mg/dL versus 11.8 +/- 1.76 mg/dL,
      respectively; P = .03). CONCLUSIONS: ESA hypo-responsiveness before KT carried
      over after KT. Low pre-transplant ERI might be a sentinel marker for PTA.

PMID- 26293058
TI  - Hyperleptinemia Is a Risk Factor for the Development of Central Arterial
      Stiffness in Kidney Transplant Patients.
AB  - BACKGROUND: Arterial stiffness could cause adverse outcomes in kidney transplant
      (KT) patients. Leptin has a role in influencing vascular smooth muscle that may
      contribute to atherosclerosis. The aim of this study was to evaluate the
      relationship between fasting serum leptin concentration and carotid-femoral pulse
      wave velocity (cfPWV) in KT patients. MATERIALS AND METHODS: Fasting blood
      samples were obtained from 55 KT patients and 65 subjects from the outpatient
      department were enrolled as the control group. The cfPWV values of >10 m/s were
      used to define as the high arterial stiffness group and <10 m/s as the low
      arterial stiffness group. The predictive ability of leptin for arterial stiffness
      of KT was assessed using receiver operating characteristic (ROC) curve and
      multivariate logistic regression analyses. RESULTS: Kidney transplant patients
      had lower hemoglobin, but higher blood urea nitrogen, creatinine, total
      cholesterol, diastolic blood pressure, intact parathyroid hormone levels, and
      leptin levels than controls. Although cfPWV levels were higher in KT patients,
      there is no difference of cfPWV levels between KT patients and control (P =
      .595). Fifteen KT patients (27.3%) were defined in the high arterial stiffness
      group, and serum leptin level was higher in the high arterial stiffness group
      compared with the low arterial stiffness group in KT patients (P < .001).
      Multivariate logistic regression analysis showed that leptin (odds ratio: 1.044,
      95% confidence interval [CI]: 1.016-1.072, P = .002) was an independent predictor
      of arterial stiffness in KT patients. The sensitivity, specificity, positive
      predictive value, negative predictive value, and area under the ROC curve
      predicting arterial stiffness in KT patients were 73.33%, 87.5%, 68.7%, 89.7%,
      and 0.828 (95% CI: 0.703-0.917, P < .001), and the leptin cut-off value was 74.14
      ng/mL. CONCLUSION: Serum fasting leptin level could predict the development of
      central arterial stiffness of KT patients.

PMID- 26293059
TI  - Twelve-Month and Five-Year Analyses of Risk Factors for New-Onset Diabetes After
      Transplantation in a Group of Patients Homogeneous for Immunosuppression.
AB  - OBJECTIVE: In the case of new-onset diabetes after transplantation (NODAT)
      development, it is suitable to reduce calcineurin inhibitors and corticosteroids.
      But change of immunosuppression can be counterproductive and can cause
      development of rejection and leads to further NODAT aggravation. METHODS: We
      retrospectively evaluated risk factors after kidney transplantation. Comparison
      groups were homogeneous in terms of administered immunosuppression, and
      individual monitored parameters were not distorted by the immunosuppression
      administered. RESULTS: In the 12-month analysis we identified these risk factors
      for NODAT: age at the time of transplantation, 50-59 years (P = .0034); age at
      the time of transplantation, >= 60 years (P < .0001); positive family anamnesis
      for diabetes mellitus type 2 (P < .0001); body mass index at the time of
      transplantation, >= 30 kg/m(2) (P = .0236); prediabetes before transplantation (P
      < .0009); and proteinuria, >0.15 g/d (P < .0002). In the 5-year analysis, we
      identified patients who were diagnosed with NODAT after the 1st year. We
      identified age >= 50 years at the time of transplantation to be an independent
      risk factors for NODAT. CONCLUSIONS: It is advisable to carry out the oral
      glucose tolerance test even in patients with physiologic levels of fasting
      glycemia.

PMID- 26293060
TI  - Renal Cell Cancer in a European Regional Renal Transplant Population: Is There a
      Role for Immediate Native Renal Radiological Surveillance Before and After
      Transplantation?
AB  - BACKGROUND: The risk of the development of renal cell cancer (RCC) in renal
      transplant recipients is several times higher than the general population. There
      can often be a delay between initial radiological imaging and patients undergoing
      renal transplantation. We present and evaluate the prevalence and clinical
      characteristics of RCC in renal transplant recipients at a single UK transplant
      center, with particular focus on tumors diagnosed in the immediate post-operative
      period, that is, likely present before transplantation. METHODS: This is a
      retrospective cohort study examining all renal transplant recipients with the
      diagnosis of RCC of native and/or graft kidneys followed up in a single UK
      transplant center. RESULTS: Between January 2002 and April 2014, 1386 patients
      underwent renal transplantation. 19 of 1386 patients had development of RCC
      (1.4%): 17 native and 2 graft tumors. The mean interval between pre-operative
      native renal imaging and transplantation was 3.5 years in 13 of 19 patients
      (range, 1-10 years). Six patients had no documented renal imaging before their
      renal transplant. The median time from transplantation to diagnosis of RCC was 5
      years (range, 1 month to 30 years). In 5 patients (26.3%), RSS developed within 6
      months of undergoing renal transplantation. CONCLUSIONS: In our study, we
      identified several patients with RCC diagnosed shortly after surgery, which
      raised the possibility that this was present before transplantation. With
      transplant recipients at increased risk of development of RCC and early detection
      key in the management of RCC, there appears to be a role for native renal
      radiological screening for patients undergoing renal transplantation.

PMID- 26293061
TI  - Mesh Hood Fascial Closure Is a Safe Alternative to Prevent Renal Allograft
      Compartment Syndrome During Kidney Transplantation.
AB  - BACKGROUND: Renal allograft compartment syndrome (RACS) is an under recognized
      yet important complication of kidney transplantation that can lead to early graft
      dysfunction and loss. The use of mesh for prevention and treatment of RACS in
      very selective circumstances has been documented previously in small case
      reports. However, it is unknown whether patient and graft survival rates are
      similar in patients undergoing renal transplantation with mesh placement for the
      prevention or treatment of RACS. The purpose of our study was to examine the risk
      factors, indications, and outcomes of mesh hood fascial closure (MHFC) use in the
      context of RACS prevention. METHODS: All patients who underwent kidney
      transplantation in our center between 2009 and 2013 were reviewed. Patients with
      mesh placed at the time of initial transplantation and secondarily at the time of
      reoperation were identified. Patient characteristics, Doppler ultrasound
      findings, and overall patient and graft survival rates were compared among
      patients with and without mesh placement. RESULTS: Of 600 patients who received a
      kidney transplant, 134 patients underwent mesh placement, 123 primarily and 11
      secondarily. Our overall 1-year patient and graft survival rates compared between
      those with and without MHFC were, respectively, 97.5% and 94.8% compared to 98.5%
      and 95.5% with P > .05. Our mesh removal rate was 6% (8/134), and the rate of
      mesh infection was 1.6% (2/134). CONCLUSIONS: We are the first to report the
      outcomes of MHFC for the prevention of RACS in patients undergoing renal
      transplantation. We found that MHFC in select circumstances has minimal risks and
      similar overall patient and graft survival rates when mesh is not used.
      Prospective studies to better understand the pathophysiology of RACS will aid in
      determining objective clinical indications for MHFC to improve allograft
      survival.

PMID- 26293062
TI  - Management of Complicated Ureteric Strictures After Renal Transplantation: Case
      Series of Pyelovesicostomy With Boari Flap.
AB  - Ureteric strictures are the most common urologic complication following renal
      transplantation. Different management options exist, ranging from temporizing
      drainage with ureteric stent or percutaneous nephrostomy tube to endoscopic
      interventions and open surgical repair. Although minimally invasive procedures
      are typically preferred, they often have a short duration of efficacy and
      multiple treatments are required. Open surgical repair allows for definitive
      management with minimal risk to the transplant. We review our experience with
      complicated ureteral strictures refractory to endoscopic management. We
      identified 10 renal transplant recipients who developed ureteric strictures that
      failed multiple endoscopic treatments. All 10 of these strictures were managed by
      means of pyelovesicostomy with the use of a Boari flap. The median time to
      ureteric stricture diagnosis was 2.5 months with a median of 4 endoscopic
      procedures before surgery. Median time from stricture diagnosis to surgical
      repair was 53 months. Overall success was 100%, with graft function being
      salvaged in all cases and no stricture recurrence after a mean follow-up of 18
      months. We present a case series of complex ureteric strictures after renal
      transplantation managed by means of pyelovesicostomy with the use of Boari flap
      after failed endoscopic management. We demonstrate the safety and effectiveness
      of this approach of to treat complex ureteric strictures. 

PMID- 26293063
TI  - Predictive Value of Unenhanced Computerized Tomography for Detecting
      Hepatosteatosis in Living Liver Donors.
AB  - OBJECTIVE: Macrovesicular hepatosteatosis is related to post-transplantation
      complications, so preoperative hepatosteatosis determination plays a critical
      role in donor selection. The aim of this study was to evaluate the efficacy of
      unenhanced computerized tomography (CT) in determining hepatosteatosis in liver
      donor candidates. METHODS: Information about donor candidates was retrospectively
      reviewed. In this screening, 27 donor candidates who underwent liver biopsy
      because of suspected hepatosteatosis in routine abdominal CT examination before
      transplantation, were reviewed. Liver biopsies and CT images were reevaluated by
      an experienced pathologist and radiologist. Macrovesicular hepatosteatosis was
      graded according to percentage and divided into 3 groups. Three radiologic liver
      attenuation indices were used: 1) hepatic attenuation value (CT(L)); 2) the
      difference between hepatic attenuation and spleen attenuation (CT(L-S)); and 3)
      the ratio of hepatic attenuation to splenic attenuation (CT(L/S)). RESULTS:
      CT(L), CT(L-S), and CT(L/S) values of donors with hepatosteatosis were
      significantly higher than the donors without hepatosteatosis. In receiver
      operating characteristic analysis, the optimal cutoff value of these indices for
      determining hepatosteatosis were; 42.5, -5, and 0.98, respectively. At these
      cutoff values, the sensitivity and specificity of these indices were calculated
      to be 80% and 75%, 93.3% and 83.3%, and 93.3% and 83.3%, respectively. There were
      no statistical differences between their diagnostic performances. When these 3
      indices were used for detect significant hepatosteatosis (>20%) it was observed
      that hepatosteatosis of only one donor could not be determined whereas it was
      seen that specificity was decreased markedly. CONCLUSIONS: Despite the high
      diagnostic yield of unenhanced CT, it is not suitable to use alone for assessment
      of hepatosteatosis in clinical practice.

PMID- 26293064
TI  - Postoperative Psychiatric Complications in Living Liver Donors.
AB  - BACKGROUND: To understand the impact of psychologic variables on donor quality of
      life, we studied long-term data on postoperative psychiatric complications in
      living liver donors. This study is a focused psychological investigation of
      diagnoses, treatments, and long-term clinical courses of living liver donors with
      psychiatric complications. METHODS: Of the 142 donors who underwent live-donor
      liver transplantation at Nagoya University Hospital between April 2004 and July
      2014, we investigated those without a history of mental illness who had developed
      such illness after transplantation and required psychiatric treatment. RESULTS: A
      total of 6 (4.2%) donors developed the following psychiatric complications after
      transplantation: major depressive disorder (n = 2), panic disorder (n = 2),
      conversion disorder (n = 1), and substance use disorder (n = 1). Concerning
      psychiatric treatment, all donors received antianxiety drugs, 3 took
      antidepressants, and supportive psychiatric therapy was concomitantly provided to
      all subjects. The average treatment period was 53.3 months. Regarding subject
      outcomes, 3 donors achieved remission, and the other 3 continued treatment. All
      subjects showed improvement in Global Assessment of Functioning Scale.
      CONCLUSION: It is important to accurately diagnose postoperative psychiatric
      complications and provide long-term treatment in close coordination with
      transplant surgeons.

PMID- 26293065
TI  - Surgical Management of Large Spontaneous Portosystemic Splenorenal Shunts During
      Liver Transplantation: Splenectomy or Left Renal Vein Ligation?
AB  - OBJECTIVE: Management of splenorenal shunt (SRS) during whole liver
      transplantation is still controversial. Splenectomy (SP) permits its radical
      removal, at the price of a specific related morbidity. Left renal vein ligation
      (LRVL) performs a downstream ligation with potential renal repercussions. This
      study aimed to compare these techniques regarding portal revascularization and
      postoperative outcomes. METHODS: From 1994 to 2012, 22 SPs and 7 LRVLs were
      performed for large SRS (>1 cm) management. RESULTS: There was no difference in
      operating times or transfusion rates. In both groups, efficient portal flow was
      initially obtained in all cases. After a median follow-up of 79 months, 2
      patients in the SP group presented an altered portal flow owing to persistence of
      a not disconnected mesentericogonadic or splenorenal shunt. Postoperative
      morbidity, including infection and portal vein thrombosis, was not significantly
      different (32% vs 14%). SP allowed a faster correction of the thrombocytopenia.
      The LRVL group had a moderate and temporary impairment of renal function.
      CONCLUSIONS: SP and LRVL represent 2 effective procedures to avoid vascular steal
      in the presence of SRS, but they require a patent portal vein. SP appears to be
      associated to specific but acceptable intraoperative morbidity, permits treatment
      of associated splenic artery aneurysm, and enables a faster correction of
      thrombocytopenia. However, the presence of a remote hilum SRS or another large
      portosystemic shunt represents a cause of failure of the procedure. LRVL is a
      safer and less demanding procedure that can suppress portal steal whatever the
      location of the SRS, but at the price of moderate renal morbidity.

PMID- 26293066
TI  - Comparison of Intraoperative Changes in Blood Glucose According to Model for End
      stage Liver Disease Score During Living Donor Liver Transplantation.
AB  - BACKGROUND: Recipients of liver transplantation (LT) may experience disturbance
      of blood glucose balance, which is aggravated by various exogenous factors. The
      Model for End-stage Liver Disease (MELD) score is an indicator of the severity of
      pretransplantation liver disease. In this study, we investigated the role of the
      MELD score in intraoperative changes in blood glucose in patients undergoing
      living donor LT (LDLT). METHODS: Perioperative data from 280 patients undergoing
      LDLT were reviewed, including glucose-related data. Intraoperatively, blood
      glucose levels were checked every hour, and the mean values at each phase of LDLT
      were calculated. Patients were divided into high and low MELD groups. An unpaired
      t-test and repeated measures analysis of variance (RMANOVA) were used in
      intergroup and intragroup comparisons of perioperative blood glucose. RESULTS:
      The high MELD group consisted of 79 patients. Both the time sequential change
      during LDLT and the interaction between perioperative blood glucose and MELD
      score were significant (RMANOVA with multivariate adjustment; P < .05).
      Pretransplant blood glucose levels did not differ between the 2 groups, but the
      mean levels of blood glucose were lower and the incidence of hypoglycemia was
      higher in the high compared with the low MELD group during all phases of LDLT (P
      < .05). CONCLUSIONS: Blood glucose levels progressively increased during LDLT
      with an interaction with the MELD score. Patients with a high MELD score had low
      blood glucose levels and a greater incidence of intraoperative hypoglycemia. MELD
      score is a useful determinant of intraoperative blood glucose levels in LDLT
      patients.

PMID- 26293067
TI  - Impact of 6% Starch 130/0.4 and 4% Gelatin Infusion on Kidney Function in Living
      Donor Liver Transplantation.
AB  - BACKGROUND: Since the first liver transplantation, pretransplantation or post
      transplantation renal problems are still among the main causes of mortality and
      morbidity. The aim of this study was to evaluate the effects of fluid replacement
      solutions used intraoperatively on renal functions in elective living-donor liver
      transplantation. METHODS: After Ethics Committee approval, informed consents were
      obtained from patients. Patients with normal renal functions and scheduled for
      elective living-donor-liver transplantation were included in the study. Patients
      were randomly allocated to infusion with 6% hydroxyehylstarch 130/40 (HES group)
      and 4% Gelofusine (GEL group). Blood samples were obtained before the induction
      of anesthesia (baseline), at the end of the operation, and postoperative days 1
      and 4. Different estimated glomerular filtration rate (eGFR) formulas using
      creatinine (modification of renal disease, chronic kidney disease-epidemiology
      collaboration and Cockraud Gault) were used to calculate the eGFR. RESULTS:
      Thirty-six patients were included in the study (GEL group = 18; HES group = 18).
      Patient characteristics, modified end stage liver disease-Child Pugh score,
      American Society of anaesthesiologist scores, and intraoperative data were
      similar between groups. Postoperative measurements showed that creatinine was
      significantly higher in the GEL group compared with the baseline, which was not
      the case for the HES group. Similarly, postoperative eGFR levels, as measured
      using MDRD and CKD-EPI, were found to be significantly lower in the GEL group.
      Postoperative urine albumin:creatinine ratios were significantly higher in the
      GEL group compared with baseline. Total crystalloid amount used, colloid, blood,
      fresh frozen plasma values, extubation, and intensive care unit (ICU) and
      hospital stay were similar in both groups. Postreperfusion syndrome developed in
      6 patients in each group. CONCLUSION: In conclusion, Gelofusine seem to cause
      more impairment in renal functions in elective living-donor liver
      transplantation.

PMID- 26293068
TI  - Quantification of Both Platelet Count and Fibrinogen Concentration Using Maximal
      Clot Firmness of Thromboelastometry During Liver Transplantation.
AB  - BACKGROUND: Rotation thromboelastometry (ROTEM(r)) is increasingly used in liver
      transplantation (LT). Of the ROTEM(r) parameters, maximum clot firmness (MCF) of
      EXTEM (MCFEXT) and INTEM (MCFINT) are influenced by both platelet count (PLT) and
      fibrinogen concentration (FIB), whereas MCF of FIBTEM (MCFFIB) is solely
      influenced by FIB. We aimed to determine whether using MCFs of thromboelastometry
      could reliably predict both PLT and FIB and to evaluate their relations in
      patients with thrombocytopenia and hypofibrinogenemia during LT. METHODS: A total
      of 4100 retrospective ROTEM(r) assays with simultaneous standard laboratory tests
      performed during LT were analyzed in 295 patients. The optimal cut-off values of
      PLT and FIB according to the ROTEM(r) transfusion guideline were determined by
      area under the curve (AUC) of receiver operating characteristic (ROC) curve
      analysis. RESULTS: MCFEXT and MCFINT showed good correlation with platelet count
      (r = 0.79 and 0.80, respectively, P < .001) and with fibrinogen concentration (r
      = 0.67 and 0.66, respectively, P < .001). MCFFIB and fibrinogen concentration
      were highly correlated (r = 0.84, P < .001). Additionally, PLT and FIB were
      calculated mathematically: PLT (/MUL) = 14827 + 3.93 (MCFEXT)(2.5); FIB (mg/dL) =
      63 + 0.00082 (MCFEXT)(3.0); FIB (mg/dL) = 29 + 13.3 MCFFIB. MCFEXT <35 mm
      predicted PLT of 43 * 10(3)/MUL (AUC = 0.89) and FIB of 91 mg/dL (AUC = 0.78),
      whereas MCFEXT <45 mm predicted PLT of 52 * 10(3)/MUL (AUC = 0.89) and FIB of 121
      mg/dL (AUC = 0.86), MCFFIB <8 mm predicted FIB of 128 mg/dL (AUC = 0.94). MCFINT
      showed almost the same cut-off values as MCFEXT. CONCLUSIONS: Both PLT and FIB
      can be reliably quantified by MCFs of thromboelastometry, reducing the needs for
      additional laboratory tests to know values of thrombocytopenia and
      hypofibrinogenemia in patients undergoing LT.

PMID- 26293069
TI  - Comparison of Postoperative Analgesic Requirements in Living Donors and Patients
      Undergoing Similar Surgical Procedures.
AB  - BACKGROUND: More factors affect pain perception of donors than patients. We
      prospectively evaluated postoperative pain intensity and analgesic requirements
      in living kidney donors and patients with renal cell carcinoma undergoing
      laparoscopic nephrectomy with similar surgical procedures. MATERIAL AND METHODS:
      The study included 30 living kidney donors and 30 patients with renal cell
      carcinoma undergoing laparoscopic nephrectomy from March 2013 to August 2014. All
      of the participants underwent similar surgical procedures under general
      anesthesia. Data including participants' demographics, surgical data,
      postoperative analgesic requirements, visual analog scale scores at rest and
      during coughing at postoperative 0.5, 2, 4, 8, 12, 24, and 48 hours, side
      effects, and overall satisfaction degree were compared between the 2 groups.
      RESULTS: Time to the first tramadol request was significantly shorter in the
      donors. The donors received more intravenous doses of tramadol than the patients.
      Visual analog scale scores at 2 and 4 hours at rest and at 2, 4, and 8 hours
      during coughing after extubation were significantly higher in the donors. There
      were no significant differences between the groups according to the number of
      participants given pethidine, time to pethidine rescue, and adverse effects. The
      overall satisfaction degree was comparable between the 2 groups. CONCLUSIONS:
      There were significant differences with respect to postoperative pain intensity
      and analgesic requirements in living kidney donors and patients undergoing
      retroperitoneal laparoscopic nephrectomy with similar surgical procedures.

PMID- 26293070
TI  - Intraoperative Continuous Veno-Venous Hemofiltration Facilitates Surgery in Liver
      Transplant Patients With Acute Renal Failure.
AB  - INTRODUCTION: We have aggressively used continuous veno-venous hemofiltration
      (CVVH) on high model for end-stage liver disease (MELD) score liver transplant
      patients with acute kidney injury and hypothesized that the addition of
      intraoperative CVVH therapy would improve overall outcomes. METHODS: We performed
      a retrospective review of all adult, single organ, liver transplant recipients
      requiring preoperative renal replacement therapy between January 1, 2011 and June
      1, 2013. Intraoperative and perioperative records and laboratory values were
      collected and used to create a database of these patients. Patients were grouped
      according to whether or not they underwent CVVH at the time of liver
      transplantation. RESULTS: Twenty-one patients with new-onset renal failure
      requiring preoperative renal replacement therapy received a liver transplant
      alone. Fourteen received intraoperative CVVH and 7 patients did not. The average
      MELD score was similar between groups (34 for intraoperative CVVH vs 35; P = .8).
      Preoperative sodium and potassium were higher for the group receiving
      intraoperative CVVH, but still fell within normal ranges. Preoperative lactate
      levels were higher in the group that received intraoperative CVVH (4.7 vs 2.0
      mmol/L; P = .01). Intraoperative CVVH did not decrease intraoperative transfusion
      requirements or intensive care unit (ICU) and hospital lengths of stay.
      Differences in reoperative rates did not reach statistical significance. All
      patients were weaned off renal replacement therapy. One-year patient survival
      rate was 86% for intraoperative CVVH versus 71% without. CONCLUSION: The
      judicious use of intraoperative CVVH therapy may permit patients with increasing
      severity of illness to achieve outcomes comparable with less ill patients.

PMID- 26293071
TI  - Single-Center Experience of Consecutive 522 Cases of Hepatic Artery Anastomosis
      in Living-Donor Liver Transplantation.
AB  - OBJECTIVE: The aim of this study was to clarify risk factors and outcome of
      hepatic arterial complication after living-donor liver transplantations (LDLT).
      METHODS: From 2004 to 2010, 522 consecutive LDLTs were performed. We used
      univariate and multivariate analysis to identify the risk factor on a
      retrospective basis, and then analysis was performed for adult cases. Hepatic
      arterial complication included thrombosis, stenosis, and pseudoaneurysm. RESULTS:
      The arterial complication rate was 4.79% (25 cases). Each complication was 9
      thromboses, 14 stenoses, and 2 pseudoaneurysms. Preoperative hemoglobin was
      significantly associated with thrombosis (P = .021), and arterial size with
      stenosis (P = .037). We could not find any association between arterial
      complications and biliary stricture. However, the outcome of biliary stricture
      treatment was associated with arterial stenosis. Of 9 cases with thrombosis, 7
      patients underwent rearterialization and 2 were treated with low-molecular-weight
      heparin (LMWH). Of 14 stenosis cases, 2 patients were treated with the use of
      balloon dilatation, 10 patients were observed under LMWH, and 2 patients
      underwent retransplantation. In cases of pseudoaneurysm, 1 patient underwent
      revision of the aneurysm and the other was observed. CONCLUSIONS: In our cohort,
      preoperative low hemoglobin level was a risk factor for thrombosis and artery
      size a risk factor for stenosis.

PMID- 26293072
TI  - Thrombin-activatable Fibrinolysis Inhibitor (TAFI) as a Novel Prognostic Factor
      After Orthotropic Liver Transplantation: A Pilot Study.
AB  - BACKGROUND: Thrombin-activatable fibrinolysis inhibitor (TAFI), a liver-produced
      coagulation factor, has been associated with higher mortality in cirrhotic
      patients, but there has not been any description of its role in perioperative
      care in liver transplantation cases. METHODS: A total of 21 patients were
      included. Serum TAFI levels were determined at 3 time points: preoperatively
      (TAFI pre), immediately postoperative (TAFI PO), and 24 hours postoperatively
      (TAFI 24 h). The main outcome was the physiological pattern of TAFI in the
      perioperative period of liver transplantation. The secondary outcomes were the
      association between TAFI and early allograft dysfunction (EAD) as well as that of
      TAFI and 6-month mortality. RESULTS: TAFI levels increased at the 24-hour time
      point, compared to the other 2 time points (TAFI pre, P = .007; TAFI PO, P =
      .0001). Early allograft dysfunction occurred in 2 of 21 patients, both
      demonstrating lower TAFI 24 h levels compared to those who did not develop this
      complication (3.0 +/- 0.2 vs 1.5 +/- 0.3; P = .0001). Three patients who died all
      demonstrated lower levels of TAFI pre (1.3 +/- 0.1 vs 2.5 +/- 0.5; P = .001) and
      TAFI PO (1.2 +/- 0.1 vs 2.4 +/- 0.4; P = .001) compared to the survivors.
      CONCLUSIONS: These findings suggest that the determination of TAFI levels-both
      pre- and postoperatively-may be of clinical relevance in liver transplant
      recipients.

PMID- 26293073
TI  - Outcomes of Early Conversion From Prograf to Generic Tacrolimus in Adult Living
      Donor Liver Transplant Recipients.
AB  - The aim of this study was to evaluate the safety and efficacy of early conversion
      from the reference tacrolimus (Prograf; Astellas Pharma, Tokyo, Japan) to the
      generic tacrolimus (Tacrobell(r):Chong Kun Dang Pharma, Seoul, Korea) in a cohort
      of adult living donor liver transplant (LDLT) recipients at a single institution.
      Between March 2010 and May 2012, a 1:1 dose conversion was performed 2 to 4 weeks
      after LDLT with dose adjustments targeted to achieve trough concentrations within
      the therapeutic range. Tacrolimus doses and trough levels, laboratory parameters,
      and adverse events were assessed. A total of 149 patients were enrolled. The
      median transplant duration was 22 days (range; 15-28 days). During a median
      follow-up of 17.3 months after conversion, there were 3 episodes of acute
      rejection, all of which responded to high-dose steroids. No adverse events were
      serious enough to stop the drug. In comparison with the control group maintained
      on Prograf, there were no significant differences in outcomes. In conclusion,
      early conversion from the reference to generic tacrolimus is safe and effective
      in stable adult LDLT patients. 

PMID- 26293074
TI  - Effect of Perioperative Terlipressin on Postoperative Renal Function in Patients
      Who Have Undergone Living Donor Liver Transplantation: A Meta-Analysis of
      Randomized Controlled Trials.
AB  - BACKGROUND: Recent studies have shown the efficacy of terlipressin on
      postoperative renal function in patients who have undergone living donor liver
      transplantation (LDLT). OBJECTIVES: To evaluate the effect of perioperative
      terlipressin on postoperative renal function in patients who have undergone LDLT
      and to analyze the hemodynamic data during transplantation surgery. STUDY DESIGN:
      A meta-analysis. METHODS: We assessed the postoperative peak serum creatinine
      level and changes in the hemodynamic data (e.g. the mean arterial pressure, heart
      rate, and systemic vascular resistance). We collected randomized controlled
      trials from PubMed, EMBASE Drugs and Pharmacology, Cochrane Controlled Trials
      Register, and Cochrane Database on Systematic Reviews. Analysis was conducted
      using RevMan 5.2. Data from each trial were pooled and weighted by their mean
      differences and corresponding 95% confidence intervals (CI). A heterogeneity
      assessment was performed. RESULTS: Three trials (151 patients) were included. The
      difference in the mean (95% CI) peak serum creatinine (mg/dL) levels
      postoperatively was not significant between the intervention and control groups
      (weighted mean difference [WMD]: -0.27; CI: -0.55-0.01; P = .06). Terlipressin
      significantly decreased heart rate during the anhepatic phase (WMD: -6.58; 95%
      CI: -8.85 to -4.31; P < .00001) with a low heterogeneity (I(2) = 41%) and
      significantly decreased heart rate during the neohepatic phase (WMD: -9.82; 95%
      CI: -11.96 to -7.68; P < .00001), although the heterogeneity was high (I(2) >
      50%). CONCLUSIONS: An intravenous infusion of terlipressin perioperatively for
      LDLT has no effect on the creatinine values postoperatively. Larger randomized
      controlled trials on terlipressin infusions during liver transplantation are
      needed.

PMID- 26293075
TI  - Rapid Detection of Bloodstream Pathogens in Liver Transplantation Patients With
      FilmArray Multiplex Polymerase Chain Reaction Assays: Comparison With
      Conventional Methods.
AB  - BACKGROUND: Bloodstream infection (BSI) is an important concern in transplant
      patients. Early intervention with appropriate antimicrobial therapy is critical
      to better clinical outcome; however, there is significant delay when conventional
      identification methods are used. METHODS: We aimed to determine the diagnostic
      performance of the FilmArray Blood Culture Identification Panel, a recently
      approved multiplex polymerase chain reaction assay detecting 24 BSI pathogens and
      3 resistance genes, in comparison with the performances of conventional
      identification methods in liver transplant (LT) patients. A total of 52 defined
      sepsis episodes (signal-positive by blood culture systems) from 45 LT patients
      were prospectively studied. RESULTS: The FilmArray successfully identified 37 of
      39 (94.8%) bacterial and 3 of 3 (100%) yeast pathogens in a total of 42 samples
      with microbial growth, failing to detect only 2 of 39 (5.1%) bacterial pathogens
      that were not covered by the test panel. The FilmArray could also detect
      additional pathogens in 3 samples that had been reported as having monomicrobial
      growth, and it could detect Acinetobacter baumannii in 2 samples suspected of
      skin flora contamination. The remaining 8 blood cultures showing a positive
      signal but yielding no growth were also negative by this assay. Results of MecA,
      KPC, and VanA/B gene detection were in high accordance. The FilmArray produced
      results with significantly shorter turnaround times (1.33 versus 36.2, 23.6, and
      19.5 h; P < .05) than standard identification methods, Vitek II, and Vitek MS,
      respectively. CONCLUSIONS: This study showed that the FilmArray appeared as a
      reliable alternative diagnostic method with the potential to mitigate problems
      with protracted diagnosis of the BSI pathogens in LT patients.

PMID- 26293076
TI  - Incidence and Predictors of Increased Coronary Calcium Scores in Liver Transplant
      Recipients.
AB  - BACKGROUND: Cardiovascular complications in liver transplant recipients are
      common. A coronary calcium score >400 determined by coronary computed tomographic
      angiography (coronary CT) provides useful information for predicting
      postoperative cardiovascular complications in liver transplant recipients.
      However, little is known about the association between risk factors and increased
      coronary calcium scores in coronary CT preformed as a preoperative cardiovascular
      evaluation before liver transplantation. We evaluated the incidence and
      cardiovascular risk factors of a coronary calcium score >400 in liver transplant
      recipients. METHODS: Between 2013 and 2014, 548 liver transplant recipients were
      analyzed retrospectively. Preoperative cardiovascular assessments and laboratory
      data were collected with coronary calcium scores. Univariate and multivariate
      logistic regression analyses were performed to evaluate cardiovascular risk
      factors of a coronary calcium score >400 in coronary CT. RESULTS: The total mean
      coronary calcium score was 103 +/- 358. Of the 548 recipients, 41 (7.5%) had a
      coronary calcium score >400. The mean coronary calcium score in patients with a
      coronary calcium score >400 was 999.7 +/- 892.1, and the mean coronary calcium
      score in patients with a coronary calcium score <= 400 was 30.1 +/- 70.9. In
      multivariate logistic regression analysis, predictors of a coronary calcium score
      >400 in liver transplant recipients were age (odds ratio [OR] = 1.05, P = .029),
      male sex (OR = 14.42, P = .009), and diabetes mellitus (OR = 2.04, P = .040).
      CONCLUSIONS: We found that old age, male sex, and diabetes mellitus were
      predictors of a coronary calcium score >400, which is associated with
      cardiovascular complications after liver transplantation. This study can provide
      useful information for preoperative cardiovascular evaluation in liver transplant
      recipients.

PMID- 26293077
TI  - Hepatocellular Carcinoma in the Setting of Chronic Hepatitis B Virus Infection:
      Tumor Recurrence and Survival Rates After Liver Transplantation.
AB  - BACKGROUND: Higher rates of hepatocellular carcinoma (HCC) recurrence after liver
      transplantation (LT) in patients with chronic hepatitis B virus (HBV) infection
      have been reported. This can influence their selection for LT and post-LT
      monitoring. OBJECTIVE: The aim of this work was to compare the rates of post-LT
      HCC recurrence and survival in HBV and non-HBV patients with the use of the
      United Network for Organ Sharing (UNOS) database. METHODS: After accessing the
      UNOS database, we analyzed patients with HCC stage T2 who underwent LT from
      cadaveric donors on or after August 24, 1998. Propensity score matching based on
      age, Model for End-Stage Liver Disease (MELD), and donor risk index was used to
      match HBV-HCC patients to HCC patients with other underlying liver diseases:
      hepatitis C virus (HCV), alcoholic liver disease (ALD), both HCV + ALD, and
      nonalcoholic steatohepatitis (NASH). Kaplan-Meier plots and multivariable
      analysis (with the use of propensity score, age, sex, and race) were used to
      assess post-LT HCC recurrence and overall survival. RESULTS: A total of 4,480 HCC
      patients were matched. Their average age was 57 +/- 7.8 years and average
      calculated MELD score was 13. Within 5 years of LT, 5.5% of patients had HCC
      recurrence and 20% died. HBV-HCC patients had 1.9 and 1.8 times higher hazard of
      tumor recurrence compared with ALD and NASH patients, respectively, and a 32%
      lower hazard of death than patients with HCV + ALD. There was no evidence of any
      other significant difference in HCC recurrence or survival among the etiology
      groups. CONCLUSIONS: HCC recurrence and survival rates following LT for HCC
      patients with chronic HBV infection are similar to those of HCC patients with
      other underlying liver diseases. These findings support LT as a viable option for
      HCC-HBV patients.

PMID- 26293078
TI  - Extreme Hyperlactatemia After Heart Transplantation: One Center's Experience.
AB  - INTRODUCTION: Hyperlactatemia may occur early after cardiac surgery and is
      correlated with prognosis. This study was conducted to analyze the perioperative
      variables and postoperative outcomes among heart transplant recipients with
      extremely high lactate levels (>15 mmol/L). METHODS: The single-center medical
      records of heart transplantation from June 2006 to May 2013 were retrospectively
      reviewed for patient characteristics, perioperative hemodynamic variables,
      arterial blood gas analysis data, and postoperative mortality. RESULTS: Among 58
      consecutive heart transplant recipients, lactate levels over the detectable upper
      limit (>15 mmol/L) were identified in 12 patients after intensive care unit
      admission, with peak time at 1.9 +/- 2.0 (range 0-6.1) hours. The maximal
      preoperative lactate level was 3.1 mmol/L, and most (11/12) postoperative lactate
      levels returned to <4 mmol/L at 27.5 +/- 12.8 hours after surgery (range 15-58,
      median 24), displaying a trend toward delayed extubation time in 10 recipients (P
      < .01). Blood glucose levels elevated significantly from preoperative 148.9 +/-
      45.2 to 375.7 +/- 96.9 mg/dL at peak lactate level (P < .01). Four patients died
      in the ICU (range 5-32 days), 4 died after discharge (range 5-57 months), with 6
      in total surviving over 1 year. CONCLUSION: Extreme hyperlactatemia commonly
      occurred early after heart transplantation and mostly recovered within 30 hours;
      however, with delayed extubation time after operation.

PMID- 26293079
TI  - Toxoplasma gondii Serology and Outcomes After Heart Transplantation: Contention
      in the Literature.
AB  - BACKGROUND: Toxoplasma gondii is an endemic pathogen to which approximately half
      of healthy patients develop antibodies. Toxoplasma serology is routinely assessed
      prior to heart transplantation. It has been suggested that donor or recipient
      toxoplasma serologic status may be associated with poor long-term outcomes post
      transplantation, but current literature reveals conflicting results. METHODS:
      From 1995 to 2012 at our single center, we retrospectively reviewed 785 heart
      transplant patients for pre-transplantation T. gondii serology. Patients were
      divided into T. gondii seronegative and seropositive groups. Subgroups in each
      group were created based on whether the donor was seropositive or seronegative.
      We assessed survival, freedom from nonfatal major adverse cardiac events, and
      freedom from cardiac allograft vasculopathy at 5 years post-transplantation.
      RESULTS: No significant difference was found between 5-year outcomes of pre
      transplant T. gondii seronegative and T. gondii seropositive recipients post
      heart transplantation. However, in the donor-seropositive/recipient-seronegative
      subgroup (D+/R-), there was a significantly lower 5-year survival rate compared
      to the cohort of donor-seronegative/recipient-seronegative (D-/R-) patients (60%
      vs 87%, P = .04). After adjustment by multivariate analysis, D+/R- status
      conferred a trend towards increased mortality (HR 3.0, P = .06). CONCLUSIONS:
      Toxoplasma serology prior to heart transplantation does not appear to impact post
      transplantation outcome. However, toxoplasma seronegative patients who receive
      toxoplasma seropositive hearts appear to have poorer 5-year survival compared to
      toxoplasma seronegative patients who received toxoplasma seronegative hearts. Due
      to the small sample size, the association between T. gondii serology mismatch and
      long-term survival warrants further study.

PMID- 26293080
TI  - Novel Method of Infection Prophylaxis in Heart Transplantation by Retrosternal
      Gentamycin Sponge Application.
AB  - BACKGROUND: Surgical wound infections are more frequent in patients undergoing
      heart transplantation than in other heart surgery patients. There is a wide
      spread of sternal wound infection incidence in transplant patients ranging from
      4% to 40%. It is first study describing local gentamicin sponge application
      during heart transplantation procedure. MATERIALS AND METHODS: We enrolled 75
      patients in a retrospective, single-center study, including 25 patients who
      underwent orthotopic heart transplantation (heart transplant group) and 50 in the
      cardiac surgery group. They were in mean age of 49 +/- 12 years and 51 +/- 13
      years in heart transplantation and cardiac surgery group, respectively. A
      gentamicin sponge was inserted intraoperatively between sternal borders before
      chest closure in all heart transplantation patients. RESULTS: There was 1 early
      death (4%) on postoperative day 7 owing to Clostridium difficile infection in the
      heart transplant group. There was 1 death (2%) in the cardiac surgery group owing
      to multiorgan failure secondary to perioperative heart ischemia. There was
      neither bacterial sternal wound infection nor sternal instability in the heart
      transplant group. None of the patients who had gentamicin sponge applied had
      wound healing problems. Two patients (4%) had a deep sternal wound infection in
      the cardiac surgery group, who had no sponge application; 1 (2%) was treated by
      surgical debridement and active drainage and 1 (2%) by vacuum therapy. There were
      11 patients (44%) discharged on insulin therapy in the heart transplant group and
      21 (21%) in the cardiac surgery group. Mean overall postoperative hospital stay
      was 35 +/- 19 days in the heart transplant group and 10 +/- 4 days in the cardiac
      surgery group. CONCLUSIONS: Gentamicin sponge is an effective local infection
      prophylaxis in heart transplant patients.

PMID- 26293081
TI  - Lung Donation After Controlled Circulatory Determination of Death: A Review of
      Current Practices and Outcomes.
AB  - BACKGROUND: Since the first reported series in 1995, transplantation of lungs
      recovered through donation after circulatory determination of death (DCDD) has
      steadily increased. In some European and Australian centers, controlled DCDD
      accounts for 15% to 30% of all transplanted lungs. Several transplant centers
      have reported early and midterm outcomes similar to those associated with the use
      of donors after brain death. Despite these encouraging reports, less than 2% of
      all lung transplants in the United States are performed using donors after
      circulatory determination of death. METHODS: An electronic search from January
      1990 to January 2014 was performed to identify series reporting lung transplant
      outcomes using controlled DCDD. Data from these publications were analyzed in
      terms of donor characteristics, donation after circulatory determination of death
      protocols, recipients' characteristics, and early and midterm outcomes. RESULTS:
      Two hundred twenty-two DCDDs were transplanted into 225 recipients. The rate of
      primary graft dysfunction grade 3 ranged from 3% to 36%. The need for
      extracorporeal membrane oxygenation support after transplantation ranged from 0%
      to 18%. The average intensive care unit stay ranged from 4 to 8.5 days and the
      average hospital stay ranged from 14 to 35 days. Thirty-day mortality ranged from
      0% to 11% and 1-year survival from 88% to 100%. CONCLUSION: Under clinical
      protocols developed and strictly applied by several experienced lung transplant
      programs, lungs from controlled DCDD have produced outcomes very similar to those
      observed with brain death donors.

PMID- 26293082
TI  - Prevalence and Diagnosis of Chronic Kidney Disease in Maintenance Lung Transplant
      Patients: ICEBERG Study.
AB  - BACKGROUND: Chronic renal dysfunction (CRD) after lung transplantation (LT) is a
      common and noteworthy complication associated with increased morbidity and
      mortality rates. The study objectives were to determine the prevalence of CRD
      according to different diagnostic criteria and describe its therapeutic
      management. METHODS: This observational, multicenter, retrospective study
      included LT patients with >= 2 years of evolution. CRD was defined according to 2
      different methods: (1) by the physician's subjective clinical criteria and (2) by
      analytical criteria (estimated glomerular filtration rate [eGFR] by Modification
      of Diet in Renal Disease of <= 59 mL/min). RESULTS: We included 113 patients;
      65.5% were men and the mean age at transplant was 49.1 (12.6) years. At 6 months
      after transplant, approximately half of patients had CRD according to analytical
      criteria, and, at 2 years after transplantation, the prevalence rose to 80%.
      Although clinical prevalence and analytical prevalence were similar (68.8% and
      78.6%), a weak concordance was observed (Kappa index: 0.6). Among patients who
      were not classified as having CRD according to clinical criteria, 40.0% (14/35)
      were diagnosed with CRD according to analytical criteria. None of the patients
      underwent renal biopsy, and 5.1% of patients required dialysis. In 77.0% of
      patients with clinical CRD diagnosis, the immunosuppressive regimen was modified:
      reduction of isolated calcineurin inhibitors (CNIs) (35.0%), CNIs decreased with
      mycophenolic acid change (23.3%), and CNIs lowering with mammalian target of
      rapamycin introduction (6.7%). In a multivariate logistic regression model, the
      independent factors associated with CRD were an older recipient age, low body
      mass index (BMI) at transplant, treatment with cyclosporine/azathioprine, and low
      eGFR at the first month after transplant. CONCLUSIONS: We found a high incidence
      of CRD at the first year after transplantation, which increased subsequently.
      Moreover, CRD was considerably underestimated by physicians' subjective clinical
      criteria. End points related to CRD development were older age, low BMI,
      azathioprine use, and low eGFR during the first month after transplant. The
      latter finding provides an opportunity to implement prevention strategies.

PMID- 26293084
TI  - Lung Transplantation for Lymphangioleiomyomatosis in a Single Japanese Institute,
      With a Focus on Late-onset Complications.
AB  - BACKGROUND: Although late-onset complications are important factors related to
      inadequate outcomes of lung transplantation (LTx), little is known about them.
      The results of LTx for lymphangioleiomyomatosis (LAM) patients, which is a large
      cohort of LTx recipients in Japan, especially with late-onset complications, are
      reported. METHODS: Thirteen consecutive LTx cases with LAM at our institute were
      evaluated, and those with late-onset complications were identified. RESULTS: The
      5-year survival rate was 69.2%. There were 4 cases with late-onset complications.
      Case 1: A 35-year-old woman who underwent right single LTx and sustained
      uncontrollable massive chylous ascites. She underwent placement of a peritoneal
      venous shunt, and the ascites was controlled. Unfortunately, she died of small
      cell cervical cancer (SCCC) 43 months after the LTx. Case 2: A 50-year-old woman
      who underwent left single LTx had pneumothorax of the native lung 16 months after
      the LTx. She underwent operative repair of the right lung with a polyglycolic
      acid (PGA) sheet. She had no recurrence of pneumothorax 1 year after the
      operation. Case 3: A 33-year-old woman, who underwent left single LTx, had
      recurrence of LAM in the transplanted lung 2 years after the LTx. She was started
      on sirolimus. Case 4: A 47-year-old woman, who underwent right single LTx,
      developed repeated high fevers. She developed an acute abdomen, and swollen
      subcutaneous lymph nodes were found. After lymph node biopsy, she was diagnosed
      as having post-transplant lymphoproliferative disorder, and she died 8 months
      after the LTx. CONCLUSION: It is hoped that these reports and the knowledge
      gained from them help improve the outcomes of LTx recipients.

PMID- 26293083
TI  - Incidence of Hepatitis E Antibodies in Swedish Lung Transplant Recipients.
AB  - BACKGROUND: Hepatitis E virus (HEV) is an important cause of acute and chronic
      hepatitis in solid organ transplant recipients, especially liver transplant
      recipients. However, less is known of the incidence and prevalence of HEV in lung
      transplant recipients. METHODS: In a prospective study, 62 patients were observed
      during the first year after lung transplantation. Sera were analyzed for anti-HEV
      immunoglobulin G (IgG) and IgM at 12 months after transplantation. Samples
      positive for anti-HEV were also analyzed for HEV RNA by polymerase chain
      reaction. Pretransplantation samples were analyzed for patients with detectable
      anti-HEV 1 year after transplantation. RESULTS: Eight patients (13%) had anti-HEV
      IgG at the 12-month follow-up sample. HEV RNA could not be detected in any of
      these samples. One of these patients seroconverted during the follow-up without
      developing acute or chronic hepatitis. CONCLUSIONS: Our results show that the
      prevalence of HEV antibodies among Swedish lung transplant recipients is similar
      when compared to the general population. It also suggests that the risk for HEV
      antibody seroconversion during first year is limited.

PMID- 26293085
TI  - Transition of Decade in Short Bowel Syndrome in China: Yesterday, Today, and
      Tomorrow.
AB  - BACKGROUND: Short bowel syndrome (SBS) patients need long-term parenteral
      nutrition or intestine transplantation. With the development of medicine,
      society, and economy over the past decade, characteristics of these patients
      might have undergone some changes. To study the issue, we conducted this
      retrospective study. METHODS: A retrospective study was conducted from January 1,
      2004, to January 1, 2014, in an intestinal rehabilitation and transplant center.
      A total of 335 SBS patients were hospitalized at our center. The patients in the
      1st 5 years were classified into group A (n = 123) and the next 5 years into
      group B (n = 212). Demographic data, medical history, and etiology of each
      patient were collected. RESULTS: The average age of group B (45.5 +/- 20.5 y) was
      significantly higher than that of group A (39.6 +/- 15.5 y). In both groups
      together, the average residual small intestine was 63.3 +/- 44.3 cm and body mass
      index (BMI) was 18.1 +/- 3.6 kg/m(2). The BMI of group B was significantly higher
      than that of group A. In serum biochemical indexes, indirect bilirubin, serum
      transferrin, fibronectin, cholesterol, blood urea nitrogen, and creatinine of the
      2 groups were significantly different. In the etiology of SBS, the mesenteric
      vascular disease and trauma decreased but radiation enteritis and nonterminal
      cancer increased. CONCLUSIONS: During the past decade, SBS patients had changed a
      lot, especially in etiology and nutritional status. In the future, the increasing
      number of nonterminal cancer and radiation enteritis patients might compromise
      the choice of intestine transplantation, and more new methods to prevent
      cholestasis need to be explored.

PMID- 26293086
TI  - Multicenter Evaluation of Current Knowledge of Intestinal Transplantation and
      Rehabilitation Among Trainee Physicians.
AB  - BACKGROUND: The management of intestinal failure has evolved dramatically over
      the last 2 decades. In addition, improved management of patients requiring
      parenteral nutrition-associated liver disease is creating a paradigm shift in
      both intestinal failure management and in the evolving indications for intestinal
      transplantation. OBJECTIVES: We conducted an evaluation measuring current
      awareness among house officers (HO) regarding nutritional and transplant
      principles in the management of intestinal disease. Our goal was to use board
      style questions with a single correct response to measure current knowledge level
      between HO. METHODS: A survey was distributed to HO via email to measure
      knowledge regarding 3 areas: principles of intestinal failure (PI), medical
      management of intestinal disease (MI), and transplantation for intestinal disease
      (TI). This was evaluated at 3 busy nontransplant centers (NTC) and a tertiary
      care intestine transplant center (TC). Statistical analysis was conducted using
      the independent samples t test and multiple linear regression analysis. RESULTS:
      Surveys were distributed to a total of 1068 HO; 208 (19.47%) responded. We
      received 139 responses (67%) from NTC and 69 (33%) from TC. 82% were postgraduate
      year (PGY) 1-3 and 18% were PGY 4-7. Of the respondents, 27% correctly answered
      questions regarding PI, 40% about MI, and 21% on TI. HO in NTC demonstrated more
      knowledge regarding PI than those in TC (P = .000). There was, otherwise, no
      difference between PGY 1-3 and PGY 4-7 (P > .05). CONCLUSIONS: This evaluation
      demonstrates potential deficiencies in the basic understanding of issues
      surrounding intestinal disease that can be used for implementation of an
      educational program regarding intestinal disease and transplantation.

PMID- 26293087
TI  - Evaluation of the Potential Risk of Hepatitis B Virus Transmission in Skin
      Allografting.
AB  - INTRODUCTION: Skin transplantation is associated with potential risk of
      infectious disease transmission; however, the exclusion of donors owing to
      hepatitis B virus (HBV) infection will worsen the shortage of allograft skin
      supply. We report a paired study to evaluate the potential risk of HBV
      transmission in skin allografting. METHODS: The presence of HBV DNA in the serum
      and skin from 37 burn patients with chronic HBV infection (CHB) was monitored by
      a HBV polymerase chain reaction (PCR) and the positive rates were compared by
      Fisher's exact probability test. RESULTS: There was a high consistency in the HBV
      serology profile between HBV DNA PCR (83.78%) and the clinical HBV test. Only 2
      patients who were positive for hepatitis B surface antigen, hepatitis B e
      antigen, and hepatitis B core antibody had detectable HBV DNA in the skin tissue;
      however, no hepatitis B surface antigen was detected as examined by
      immunohistochemistry staining. There was a significant difference between the
      positive rates of HBV DNA in the serum and skin (chic(2) = 27.03; P < .001).
      CONCLUSIONS: The potential risk for HBV transmission by skin allografting is very
      low. Given that China has a large population of patients with HBV, the acceptance
      of skin from donors with CHB to the skin bank would increase the number of tissue
      donations to meet the urgent medical need for skin transplantation.

PMID- 26293088
TI  - Is Mexico Ready for Face Transplantation?
AB  - With the limitations of surgical reconstructive procedures, the growing number of
      gunshot wounds, burns, and work accidents in Mexico that result in complex facial
      deformities leaves only 1 option-face transplantation. The National Institute of
      Medical Sciences and Nutrition "Salvador Zubiran" (INCMNSZ) has performed
      transplants since 1971. We at INCMNSZ undertook the 1st bilateral upper-limb
      transplantation in Latin America in 2012. We are willing to continue in this
      manner toward conducting face transplantation at our institute. To this end, we
      identified and solved various challenges. The 1st challenge was acceptance and
      inclusion of vascularized composite allotransplantation (VCA) within general
      Mexican health law and approval of the face transplantation procedure.
      Subsequently, the health ministry provided a license to INCMNSZ to perform the
      procedure. The 2nd challenge concerned who would pay for the procedure. The costs
      will be paid by the patient (1st-party payer), social security institutions (2nd
      party payers), and the health ministry (3rd-party payer). The 3rd challenge was
      to maintain ongoing surgical training of the team using cadavers. The fourth
      challenge was to locate donors; toward this end, we developed a campaign for
      promoting face donation in social media, making a comic book, and training organ
      and tissue coordinators to further VCA. Thus, INCMNSZ has the legal,
      administrative, medical, and surgical wherewithal to accomplish face
      transplantation. 

PMID- 26293089
TI  - Galectin-9 in Combination With EX-527 Prolongs the Survival of Cardiac Allografts
      in Mice After Cardiac Transplantation.
AB  - Galectin-9 (Gal-9), a member of the galectin family, has a variety of biologic
      activities. However, its role in allografts is not fully clarified yet. The
      relationship between interleukin-17 (IL-17) and Gal-9 and the role of Gal-9 in
      T(H)17-cell differentiation also remain unclear. We built a murine cardiac
      transplantation model, which we treated with Gal-9 and/or EX-527, a specific
      Sirtuin-1 inhibitor. Afterwards, flow-cytometric analysis and reverse
      transcription polymerase chain reaction were used to detect the number of T(H)17
      cells and the expression of key factors involved in the differentiation of T(H)17
      cells; in addition, the survival times of cardiac transplanted mice in different
      groups were recorded. The levels of circulating T(H)17 cells were found to
      increase in the peripheral blood of mice that exhibited acute rejection (AR)
      after heart transplantation, which was determined to be correlated with the
      rejection grade. Gal-9 or EX-527 can inhibit the activation and differentiation
      of T(H)17 cells and effectively suppress T(H)17-cell-mediated AR. These data
      provide new evidence for the potential regulatory effects of Gal-9 in alloimmune
      responses in a murine model of heart transplantation, and suggest the combined
      use of galectin-9 and EX-527 may be a powerful method to induce tolerance of
      fully mismatched murine cardiac allografts.

PMID- 26293090
TI  - Effects of Monocyte Chemotactic Protein-1 and Nuclear Factor of Kappa B Pathway
      in Rejection of Cardiac Allograft in Rat.
AB  - BACKGROUND: Graft rejection is a key obstacle to successful heart
      transplantation. We sought to investigate the expression and role of monocyte
      chemotactic protein-1 (MCP-1) in rejection of cardiac allografts, as well as the
      role of the nuclear factor of kappa B (NF-kappaB) pathway. METHODS: Heterotopic
      cervical heart transplantation was performed using a modified cuff-technique.
      Recipient rats (n = 12) underwent acute rejection (AR) without any treatment (AR
      group). The remaining rats (3 groups; n = 12/group) were treated with
      Cyclosporine A (CsA; CsA group), immunologic tolerance (IT; IT group), and
      pyrrolidine dithiocarbamate (PDTC; NF-kappaB inhibitor; PDTC group). We studied
      the inflammatory infiltration and myocardial fibrosis of cardiac allografts with
      hematoxylin-eosin (HE) and Masson staining, and detected the expression of MCP-1
      by immunohistochemistry and Western blotting. Cardiac allograft vasculopathy
      (CAV) also was evaluated using van Gieson staining. RESULTS: The survival time of
      the PDTC group (142.37 +/- 24.28 days) was significantly longer than that of the
      AR group (6.54 +/- 2.47 days; P = .00073) and the CsA group (93.51 +/- 20.17
      days; P = .0052). Myocardial fibrosis and CAV in the PDTC group were
      significantly attenuated compared with the CsA group (P < .01). The expression of
      MCP-1 in the IT group was markedly lower than in the other 3 groups (P < .05).
      The expression of MCP-1 in the PDTC group was also significantly lower than the
      CsA group (1.15 +/- 0.27 vs 1.58 +/- 0.17; P = .016). CONCLUSION: These findings
      suggest that the expression level of MCP-1 could be monitored to reflect the
      severity of cardiac allograft rejection. PDTC can significantly prevent the
      rejection of cardiac allografts by inhibiting MCP-1 expression via the
      suppression of the NF-kappaB pathway.

PMID- 26293091
TI  - Identification of Suitable Reference Genes for Normalization of Real-Time
      Quantitative Polymerase Chain Reaction in an Intestinal Graft-Versus-Host Disease
      Mouse Model.
AB  - BACKGROUND: With the development of real-time quantitative polymerase chain
      reaction (RT-qPCR) and intensive research on acute graft-versus-host disease
      (GVHD), selecting the best reference gene for normalization of RT-qPCR analysis
      in a GVHD model becomes more and more important. In this study, we aimed to
      identify suitable reference genes for mRNA studies in an intestinal GVHD mouse
      model after bone marrow transplantation (BMT). METHODS: BALB/c recipients
      received 7.5 Gy total body irradiation (TBI) followed by injection of 5 * 10(6)
      bone marrow cells, without infusion of spleen cells for BMT, with infusion of 5 *
      10(5) or 2.5 * 10(6) spleen cells for mild or moderate GVHD, respectively.
      Healthy mice were chosen as normal control subjects. Duodenum, jejunum, ileum,
      colon, and small intestine were collected at days 7, 14, 21, and 28 after
      transplantation. Transcription levels of 9 candidate genes, B2M, SDHA, HPRT,
      ACTB, GAPDH, HMBS, TBP, YWHAZ, and RPLP0, in each tissue were measured with the
      use of RT-qPCR. Combined data from these tissues in each group were defined as
      all samples. The expression stability of these genes was analyzed with the use of
      Genorm, Normfinder, Bestkeeper, and DeltaCt. RESULTS: Our results showed that in
      all samples, ACTB and HMBS displayed the highest and lowest expression levels,
      respectively. Genorm identified HRPT and SDHA as the most stable reference genes,
      whereas Normfinder and DeltaCt method showed HPRT as the most stably expressed
      gene. Bestkeeper ranked YWHAZ and HPRT as the top 2 most suitable genes. In
      conclusion, HPRT was recommended as the most suitable reference gene after
      comprehensive ranking, suggesting that it could be used as an internal control
      for mRNA studies in intestinal GVHD after BMT.

PMID- 26293092
TI  - Improved Cuff Technique for Establishing a Mouse-Rat Heterotopic Cardiac
      Xenotransplantation Model.
AB  - BACKGROUND: The small animal model of cardiac transplantation is the most common
      model in organ transplantation studies. The cervical heterotopic transplantation
      is widely performed because this allows for direct observation of the graft
      heartbeat and contributes to early prediction of graft rejection. OBJECTIVE: A
      mouse-rat cervical heterotopic cardiac xenotransplantation model was modified
      with respect to the anesthesia method, cardiac graft harvesting method, and
      perioperative treatment. These improvements ensure the stability and reliability
      of xenotransplantation models for in vivo studies of immune-mediated graft
      rejection. METHODS: After establishing isoflurane inhalation anesthesia, the
      donors' hearts were harvested. The experimental method involved separate ligation
      of the left and right superior venae cavae; the other blood vessels were ligated
      in a cluster. Both the donor and recipient animals were placed on a heating pad
      intraoperatively to maintain a body temperature of 37-40  degrees C. The model
      establishment was divided into 3 stages: practice, stabilization, and
      stereotyping. The surgical success rate and operation time were recorded.
      Specimens were harvested at different time points for histopathological
      examination. RESULTS: The anesthetic effect of isoflurane was well maintained,
      and no animals died of adverse anesthetic events. Body temperature was maintained
      at 37-40  degrees C which effectively shortened the time to restoration. The
      modification of the cardiac graft harvesting method is conducive to rebeating of
      the donor heart. The success rates in the stabilization and stereotyping stages
      were significantly higher than that in the practice stage (P < .05). The
      operation time in the stabilization and stereotyping stages were significantly
      shorter than those in the practice stage (P < .05). Histopathological examination
      revealed thrombosis formation, interstitial hemorrhage, and inflammatory cell
      infiltration in the donor hearts. CONCLUSION: Our findings suggest that the mouse
      rat cervical heterotopic cardiac xenotransplantation model is the ideal animal
      model for studying xenograft rejection.

PMID- 26293093
TI  - Antiproteinuric Effects of Green Tea Extract on Tacrolimus-Induced Nephrotoxicity
      in Mice.
AB  - INTRODUCTION: It has been reported that proteinuria is an early predictive marker
      in detection of tacrolimus (TAC) nephrotoxicity. The aim of this study was to
      investigate the antiproteinuric effects of green tea extract (GTE) on TAC-induced
      acute nephrotoxicity in mice. METHODS: The mice (n = 20) were divided into 4
      groups (n = 5 per group); control group mice were intraperitoneally (IP) injected
      with 0.9% saline, TAC group mice were IP injected with TAC 1 mg/kg, and inducible
      nitric oxide synthase (iNOS) inhibitor group mice were given in addition NG-nitro
      L-arginine-methyl ester 12 mmol/L by subcutaneous injection. TAC-GTE group mice
      were given TAC by IP injection and GTE 100 mg/kg by subcutaneous injection.
      RESULTS: The 24-hour urine protein amounts were significantly increased in TAC
      group mice (36.1 +/- 9.9 mg/d) compared with control group mice (13.3 +/- 5.4
      mg/d) and significantly decreased in TAC-GTE group mice (19.1 +/- 6.9 mg/d, P <
      .01) compared with TAC group mice. The nitric oxide (NO) production by TAC was
      significantly suppressed by GTE and iNOS inhibitor injection. Renal tissue
      malondialdehyde (MDA) level was significantly increased in the TAC group compared
      with the control group and was significantly decreased in the TAC-GTE group
      compared with that of the TAC group. The antioxidant enzyme activities of
      superoxide dismutase and catalase were significantly suppressed in the TAC group
      compared with the control group and were restored in the GTE injection group.
      CONCLUSIONS: GTE treatment has beneficial antiproteinuric effects on TAC-induced
      acute renal injury in mice.

PMID- 26293094
TI  - Improved Proliferation and Differentiation of Bone Marrow Mesenchymal Stem Cells
      Into Vascular Endothelial Cells With Sphingosine 1-Phosphate.
AB  - The practical use of bone marrow mesenchymal stem cells (MSCs), considered to be
      the best candidate in the field of regenerative medicine, is limited by the low
      efficiency of MSC differentiation. Sphingosine 1-phosphate (S1P) could promote
      proliferation, survival, and differentiation of many types of cells, but its
      effects on MSCs remain elusive. In this study, S1P was added during primary MSCs
      (PR-MSCs) culture and the effects of S1P on proliferation, survival, and
      differentiation of PR-MSCs were evaluated. The results showed that S1P could
      improve PR-MSCs proliferation activity in a concentration-dependent manner, and
      the apoptosis of PR-MSCs cultured in hypoxia was significantly reduced in the S1P
      treated group compared to the control group. After being cultured with vascular
      endothelial growth factor for 7 days, the specific genes of endothelial cells
      were highly expressed in S1P-treated PR-MSCs compared to control group, which
      coincided with the augumented production of hepatocyte growth factor, stromal
      cell-derived factor-1, and insulin-like growth factor-1. In summary, our results
      suggest that S1P can promote proliferation, survival, and differentiation into
      vascular endothelial cells of PR-MSCs. These results will promote the clinical
      application of PR-MSCs and deepen our understanding of the function mechanism of
      S1P.

PMID- 26293095
TI  - Nicotinamide Facilitates Mesenchymal Stem Cell Differentiation Into Insulin
      Producing Cells and Homing to Pancreas in Diabetic Mice.
AB  - OBJECTIVE: This study aimed to investigate the effect of nicotinamide on
      differentiation of mesenchymal stem cells (MSCs) into insulin-producing cells
      (IPCs) in vivo in mice and on homing of MSCs to the pancreas after being
      intravenously infused. METHODS: Streptozotocin (STZ)-induced diabetic Balb/c mice
      received syngeneic transplantation of carboxyfluorescein succinimidyl ester
      (CFSE)-labeled bone marrow MSCs into the liver or tail vein. Nicotinamide was
      intraperitoneally injected into mice at a dose of 500 mg/kg body weight per day
      after STZ administration. Mice who received saline solution injection instead of
      nicotinamide were involved as control. RESULTS: Mice that received nicotinamide
      injection showed lower blood glucose, higher serum insulin, and more improved
      glucose tolerance compared with the control group. Immunohistochemistry analysis
      showed that higher levels of insulin staining and higher percentages of
      CFSE+/insulin+ cells were observed in the liver and pancreas sections of mice who
      received nicotinamide injection compared with the control group. The percentage
      of CFSE+/insulin+ cells was positively correlated with serum insulin level. Real
      time polymerase chain reaction results showed that the implanted MSCs in mice who
      received nicotinamide injection exhibited higher levels of beta-cell-related gene
      expression than the control group. More CFSE-labeled MSCs appeared in the
      pancreas of mice who received nicotinamide injection compared with the control
      group after being intravenously infused, whereas the amount of CFSE-labeled MSCs
      in the liver was not affected by nicotinamide injection. CONCLUSIONS:
      Nicotinamide facilitates MSCs differentiating into functional IPCs in vivo in
      diabetic mice and promotes intravenously infused MSCs to home to the pancreas.

PMID- 26293096
TI  - Mesenchymal Stem Cell Modulates T Follicular Helper Cell to Induce
      Immunotolerance of Islet Allograft.
AB  - OBJECTIVE: To verify whether mesenchymal stem cells protected the islet allograft
      via modulating follicular B helper T cells (Tfh) cells. METHODS: The recipient
      mice were divided into 5 groups. Group A: the diabetic group (n = 12); Group B:
      islets alone group (n = 12); Group C: MSCs and islets co-transplanted group (n =
      12, MSCs = 0.5 * 10(6)); Group D: MSCs and islets co-transplanted group (n = 12,
      MSCs = 1 * 10(6)); Group E: MSCs and islets co-transplanted group (n = 12, MSCs =
      2 * 10(6)); One control group of normal NOD mice was set as well. ELISA was used
      to examine the autoantibody level of GAD65 Ab, insulin autoantibodies, and
      insulin. The Tfh count was determined by fluorescence-activated cell sorting. The
      insulin expression of islet grafts, the infiltration of lymphocytes, and the Tfh
      cells were observed via hematoxylin and eosin staining and immunohistochemical
      staining. RESULTS: There was significant prolonged graft survival and more
      insulin expression of islet grafts observed in the co-transplant group. A lower
      level of the Tfh cells and autoantibody GAD65 Ab, insulin autoantibodies were
      also presented in the co-transplant group (P < .01). The infiltration of
      lymphocytes in the co-transplant group was notably less than in the islet-alone
      group (P < .01). CONCLUSIONS: Mesenchymal stem cells were able to protect the
      islet allograft by regulating the follicular helper T cells.

PMID- 26293097
TI  - 2-Methoxyestradiol: A Hormonal Metabolite Modulates Stimulated T-Cells Function
      and proliferation.
AB  - BACKGROUND: 2-Methoxyestradiol (2ME2) is an endogenous metabolite of estrogen
      that is nonestrogenic and has been studied in cancer as an antimitotic agent that
      is beneficial by its selectivity for cancer cells without toxicity to
      nonmalignant cells. Because the effect of 2ME2 in a transplant rejection setting
      remains unknown, we hypothesized that 2ME2 can inhibit stimulated T-cell
      function. METHODS: Human peripheral blood mononuclear cells (PBMCs) were cultured
      and pretreated with 2ME2 before stimulation. The cultured medium was collected
      for enzyme-linked immunosorbent assays, and whole-cell lysates were collected for
      Western immunoblotting. Proliferation and apoptosis assays were performed and
      analyzed by means of flow cytometry. RESULTS: Tumor necrosis factor -alpha and
      interferon-gamma cytokine production in 2ME2-treated stimulated PBMCs were
      modestly reduced relative to control samples. T-cell proliferation was blunted by
      treatment with 2ME2, and a decrease in apoptosis correlated with a decrease in
      caspase-9 activity. Additionally, 2ME2 was able to block stress-induced
      senescence caused by stimulation of T-cells. CONCLUSIONS: 2ME2 is a hormone-based
      therapy that blunts stimulated T-cell proliferation and does not induce apoptosis
      or stress-induced senescence. Stimulated T-cells treated with 2ME2 are still able
      to produce normal levels of cytokines. Therefore, 2ME2 may lead to an oral
      immunomodulatory adjunct therapy with a low side effect profile for individuals
      undergoing transplantation.

PMID- 26293099
TI  - RE: Anesthetic Management for Resection of Hepatic Paraganglioma Metastatic From
      the Donor Organ in an Orthotopic Liver Transplant Recipient: A Case Report.

PMID- 26293098
TI  - Distribution of Porcine Endogenous Retrovirus in Different Organs of the Hybrid
      of a Landrace and a Jeju Domestic Pig in Korea.
AB  - Xenotransplantation offers a solution to the shortage of available organs for
      transplantation, and the pig represents an ideal source of such organs. However,
      porcine endogenous retrovirus (PERV), whose genome is integrated in pigs, has
      been suggested to pose a potential risk of xenotransmission. Expression of PERVs
      in different organs of pigs was carefully measured at DNA, mRNA, and protein
      levels, providing information valuable for the application of pig organs in
      xenotransplantation. An analysis of PERV DNA showed that a very similar number of
      PERV copies was present in the genome of all organs, whereas mRNA and protein
      levels of PERV varied depending on the organ, with kidney, liver, and spleen
      expressing high levels of both mRNA and protein. In contrast, mRNA and protein
      levels were dissimilar in the lung and brain, where mRNA levels were low but
      protein levels were high. This discrepancy indicates that mRNA levels are not
      always reflected in protein expression. In addition, the difference between mRNA
      and protein highlights the importance of choosing the proper analysis method for
      diagnosing viral infection. In summary, this study provides insight into the
      distribution of PERV in various organs at the DNA, mRNA, and protein levels, and
      also informs the proper selection of tissues or organs for future clinical
      xenotransplantation. 

PMID- 26293100
TI  - Re: Complete Clinical Remission of Psoriasis 6 Months After Renal
      Transplantation.

PMID- 26293101
TI  - Response.

PMID- 26293102
TI  - Heart Transplantation for End-Stage Heart Failure Due to Cardiac Sarcoidosis.

PMID- 26293103
TI  - Response.

PMID- 26293105
TI  - Response.

PMID- 26293104
TI  - Re: Impact of Donor-to-Recipient Weight Ratio on Survival After Bilateral Lung
      Transplantation.

PMID- 26293106
TI  - RE: Marginal Donors in Renal Transplantation.

PMID- 26293107
TI  - Response.

PMID- 26293108
TI  - The effect of topical treatment and psoriasis severity on serum retinol-binding
      protein-4 levels.
AB  - OBJECTIVE: Psoriasis has been considered as chronic systemic disease. Retinol
      binding protein-4 (RBP-4) might play a role in psoriasis and its comorbidities.
      The aim of this study was to investigate the associations between serum RBP-4
      levels and disease severity, indicators of inflammation or metabolic syndrome and
      changes after topical treatment in psoriatic patients. METHODS: Thirty-seven
      patients with relapse of plaque-type psoriasis and 16 healthy volunteers were
      examined. Blood samples were collected before and after 14 days of therapy. Serum
      RBP-4 concentrations were examined by enzyme-linked immunosorbent assay for
      correlation with psoriasis area and severity index (PASI), body mass index (BMI),
      inflammatory and biochemical markers and with efficacy of topical treatment.
      RESULTS: RBP-4 serum levels were increased in psoriatics compared to the
      controls, but without statistical significance (p = 0.2). No significant
      correlations between investigated adipokine and several indicators of metabolic
      disorders, nor BMI or PASI were found. A significant negative correlation with
      CRP was noted. After topical treatment serum RBP-4 level did not significantly
      change (p = 0.3), despite clinical improvement. CONCLUSION: RBP-4 might have a
      protective role in terms of chronic inflammation and comorbidities of psoriasis.
      The adipokine is presumably not useful in determining severity and the
      effectiveness of antipsoriatic treatment.

PMID- 26293109
TI  - Evaluating the effect of biofilm thickness on nitrification in moving bed biofilm
      reactors.
AB  - This study evaluates the effect of biofilm thickness on the nitrifying activity
      in moving bed biofilm reactors (MBBRs) in a controlled environment. In-depth
      understanding of biofilm properties in MBBRs and their effect on the overall
      treatment efficiency is the key to optimizing process stability and efficiency.
      However, evaluating biofilm properties in continuously operated MBBRs can be
      extremely challenging. This study uses a carrier design which enables comparison
      of four different biofilm thicknesses, in otherwise equally operated lab-scale
      MBBRs. The results show that within the studied range (200-500 um) and specific
      operation conditions, biofilm thickness alone had no significant effect on the
      overall ammonium removal. The nitrate production, however, decreased with a
      decreasing biofilm thickness, and the ratio between nitrite and ammonia-oxidizing
      activity decreased both with increasing load and decreasing oxygen concentration
      for all thicknesses. The suggestion that nitratation is disfavoured in thin
      biofilms is an interesting contribution to the current research being performed
      on nitrite-oxidizing bacteria inhibition for deammonification applications. By
      indicating that different groups of bacteria respond differently to biofilm
      thickness, this study accentuates the importance of further evaluation of these
      complex systems. 

PMID- 26293110
TI  - Novel glucocorticoid receptor agonists in the treatment of asthma.
AB  - INTRODUCTION: Inhaled corticosteroids are the only drugs that effectively
      suppress the airway inflammation, but they can induce considerable systemic and
      adverse effects when they are administered chronically at high doses.
      Consequently, the pharmaceutical industry is still searching for newer entities
      with an improved therapeutic index. AREAS COVERED: Herein, the authors review the
      research in the glucocorticoid field to identify ligands of the glucocorticoid
      receptor (GR). These ligands preferentially induce transrepression with little or
      no transactivating activity, in order to have a potent anti-inflammatory action
      and a low side-effects profile. EXPERT OPINION: Several agents have been
      synthesized, but few have been tested in experimental models of asthma.
      Furthermore, only three (BI-54903, GW870086X and AZD5423) have entered clinical
      development, although the development of at least one of them (BI-54903) was
      discontinued. The reason for the limited success so far obtained is that the
      model of transactivation versus transrepression is a too simplistic
      representation of GR activity. It is difficult to uncouple the therapeutic and
      harmful effects mediated by GR, but some useful information that might change the
      current perspective is appearing in the literature. The generation of gene
      expression 'fingerprints' produced by different GR agonists in target and off
      target human tissues could be useful in identifying drug candidates with an
      improved therapeutic ratio.

PMID- 26293111
TI  - Silicon photonic crystal thermal emitter at near-infrared wavelengths.
AB  - Controlling thermal emission with resonant photonic nanostructures has recently
      attracted much attention. Most of the work has concentrated on the mid-infrared
      wavelength range and/or was based on metallic nanostructures. Here, we
      demonstrate the experimental operation of a resonant thermal emitter operating in
      the near-infrared (~1.5 MUm) wavelength range. The emitter is based on a doped
      silicon photonic crystal consisting of a two dimensional square array of holes
      and using silicon-on-insulator technology with a device-layer thickness of 220
      nm. The device is resistively heated by passing current through the photonic
      crystal membrane. At a temperature of ~1100 K, we observe relatively sharp
      emission peaks with a Q factor around 18. A support structure system is
      implemented in order to achieve a large area suspended photonic crystal thermal
      emitter and electrical injection. The device demonstrates that weak absorption
      together with photonic resonances can be used as a wavelength-selection mechanism
      for thermal emitters, both for the enhancement and the suppression of emission. 

PMID- 26293112
TI  - A biochemical screening approach to putatively differentiate mammalian pathogenic
      Oomycota species in the clinical laboratory.
AB  - The report of four novel mammalian pathogenic species of the genus Lagenidium
      prompted us to study the use of biochemical assays to differentiate the Oomycota
      mammalian pathogens Pythium insidiosum and Lagenidium spp. We investigated the
      reaction of 23 Lagenidium and eight Pythium species in various biochemical
      assays. Because the morphological features of the Oomycota species are similar to
      those of species in the Entomophthoramycota and Mucormycota, five fungal species
      with coenocytic hyphae were also included. We found that mammalian and plant
      isolates of Pythium spp. all hydrolysed sucrose, but Lagenidium species and the
      fungal strains did not. In addition, both Pythium spp. and Lagenidium spp. were
      found to be maltose-positive, whereas fungal strains did not hydrolyse this
      sugar. The fungal species and thermo-sensitive Lagenidium giganteum and
      Lagenidium humanum were urease-negative, but the mammalian Lagenidium spp. and
      Pythium spp. hydrolysed urea within 24  h. These findings suggest these assays
      can be used for the presumptive differentiation of mammalian Oomycota species in
      the laboratory.

PMID- 26293113
TI  - Roles of the TonB1 and TonB2 proteins in haemin iron acquisition and virulence in
      Riemerella anatipestifer.
AB  - Two TonB systems in Riemerella anatipestifer were found and characterized as
      ExbB1-ExbD1-TonB1 and ExbB2-ExbD2-ExbD2'-TonB2, but the significance of two sets
      of TonB complexes in R. anatipestifer is not clear. In this study, by deleting
      the tonB1 or tonB2 gene of R. anatipestifer strain CH3, we investigated the roles
      of the TonB1 and TonB2 proteins in iron acquisition and virulence. The results
      showed that strain CH3 could utilize haemin as the sole iron source in the
      presence of l-cysteine, but haemin iron acquisition was defective in the
      CH3DeltatonB1 mutant, and the deletion of either tonB1 or tonB2 significantly
      reduced adhesion to and invasion of Vero cells. Animal experiments indicated that
      the LD50 of the CH3DeltatonB1 and CH3DeltatonB2 mutants in ducklings was ~224-
      and ~87-fold, respectively, higher than that of the WT CH3 strain. Additional
      analysis indicated that blood bacterial loading of ducklings infected with
      CH3DeltatonB1 or CH3DeltatonB2 decreased significantly compared with that found
      for WT CH3-infected ducklings. Thus, our results indicated that the TonB1, but
      not TonB2 protein, is involved in haemin iron acquisition and that both TonB
      proteins are necessary for optimal bacterial virulence. 

PMID- 26293114
TI  - Influence of personality psychology on outcome of total hip arthroplasty: a cross
      sectional study on 69 patients.
AB  - AIM: Patient's satisfaction after total hip arthroplasty is influenced by many
      surgical and rehabilitation aspects, but is not available in the literature, a
      study that analyses the correlation between patient's psychology and clinical
      results of this procedure. The aim of this study was to investigate the
      relationship between memory of pain, clinical outcome and subjective satisfaction
      with the Multidimensional Health Locus of Control. METHODS: We conducted a cross
      sectional study on a cohort of 69 patients operated of total hip arthroplasty in
      our department from November 2008 to August 2011. Pre- and post-operative hip
      function was assessed by the Harris Hip Score. At the follow-up visit, patient
      satisfaction was assessed by means of the Patient Satisfaction Questionnaire. The
      memory of pain was evaluated by a modified questionnaire of pain experience.
      Multidimensional Health Locus of Control was evaluated in all patients, and
      results were connected with patient's subjective satisfaction and pain indexes.
      RESULTS: Patients were divided into two groups about patient satisfaction, those
      with GPS > 15 and those with GPS <= 15. Patients very satisfied showed a
      significantly higher mean value of IHLC. Regarding pain experience, patients were
      divided into two categories: those recalling less pain with OvP score <=11 (Q1 <
      3, avg. score Q2-Q4 <= 3) and those recalling more pain with OvP score >11. IHLC
      score resulted significantly higher in patients recalling less pain. DISCUSSION:
      Multidimensional Health Locus of Control can be considered a predictor of
      patient's satisfaction after an invasive surgical procedure as total hip
      arthroplasty.

PMID- 26293115
TI  - Enhanced electrochemical performance of a ZnO-MnO composite as an anode material
      for lithium ion batteries.
AB  - A ZnO-MnO composite was synthesized using a simple solvothermal method combined
      with a high-temperature treatment. To observe the phase change during the heating
      process, in situ high-temperature XRD analysis was performed under vacuum
      conditions. The results indicated that ZnMn2O4 transformed into the ZnO-MnO
      composite phase starting from 500  degrees C and that this composite structure
      was retained until 700  degrees C. The electrochemical performances of the ZnO
      MnO composite electrode were evaluated through galvanostatic discharge-charge
      tests and cyclic voltammetry analysis. Its initial coulombic efficiency was
      significantly improved to 68.3% compared to that of ZnMn2O4 at 54.7%.
      Furthermore, the ZnO-MnO composite exhibited improved cycling performance and
      enhanced rate capability compared with untreated ZnMn2O4. To clarify the
      discharge-charge mechanism of the ZnO-MnO composite electrode, the structural
      changes during the charge and discharge processes were also investigated using ex
      situ XRD and TEM. 

PMID- 26293116
TI  - Peptidylarginine deiminase type 4 deficiency reduced arthritis severity in a
      glucose-6-phosphate isomerase-induced arthritis model.
AB  - Peptidyl arginine deiminase 4 (PAD4) is an enzyme that is involved in protein
      citrullination, and is a target for anti-citrullinated peptide antibodies (ACPAs)
      in rheumatoid arthritis (RA). Genetic polymorphisms in the PADI4 gene encoding
      PAD4 are associated with RA susceptibility. We herein analyzed the roles of PADI4
      in inflammatory arthritis using a glucose-6-phosphate isomerase (GPI)-induced
      arthritis (GIA) model in Padi4 knockout (KO) mice. Arthritis severity, serum anti
      GPI antibody titers, and IL-6 concentrations were significantly reduced in Padi4
      KO mice. The frequency of Th17 cells was decreased in GPI-immunized Padi4 KO
      mice, whereas WT and Padi4-deficient naive CD4(+) T cells displayed the same
      efficiencies for Th17 cell differentiation in vitro. In addition, the numbers of
      myeloid lineage cells were reduced with the increased expression of pro-apoptotic
      genes in GPI-immunized Padi4 KO mice. Furthermore, the survival of Padi4
      deficient neutrophils was impaired in vitro. Our results suggest that PADI4
      exacerbates arthritis with diverse immunological modifications. 

PMID- 26293118
TI  - Causal effect of vitamin D on prostate cancer using Mendelian randomization
      approach.

PMID- 26293117
TI  - The detection of significant prostate cancer is correlated with the Prostate
      Imaging Reporting and Data System (PI-RADS) in MRI/transrectal ultrasound fusion
      biopsy.
AB  - PURPOSE: To evaluate the performance of real-time MRI/ultrasound (MRI/US) fusion
      guided targeted biopsy (TB) in men with primary and repeat biopsies and correlate
      the prostate cancer detection rate (CDR) with the PI-RADS score. METHODS:
      Analysis included 408 consecutive men with primary and prior negative biopsies
      who underwent TB and 10-core random biopsy (RB) between January 2012 and January
      2015. TB was performed with a real-time MRI/US fusion platform with sensor-based
      registration. Clinically significant PCa was defined as Gleason score (GS) >= 7
      or GS 6 with maximal cancer core length >= 4 mm for TB and according to Epstein
      criteria for RB. RESULTS: The overall CDR was 56 % (227/408). The CDR for primary
      biopsy was 74 % (60/81) and 57 % (67/117), 49 % (62/126), 45 % (38/84) for
      patients with 1, 2 and >= 3 prior negative biopsies. CDRs correlated with PI-RADS
      2/3/4/5 were 16 % (5/32), 26 % (29/113), 62 % (94/152) and 89 % (99/111),
      respectively. The rates of significant tumors in relation to PI-RADS 2/3/4/5 were
      60 % (3/5), 66 % (19/29), 74 % (70/94), 95 % (94/99). In 139 (61 %) cases with
      radical prostatectomy (RP), the rates of >= pT3 tumors in correlation with PI
      RADS 4 and 5 were 20 % (11/56) and 49 % (32/65). PI-RADS constituted the
      strongest predictor of significant PCa detection (p < 0.007). CONCLUSIONS: Real
      time MRI/US fusion-guided TB combined with RB improved PCa detection in patients
      with primary and repeat biopsies. The CDR was strongly correlated with a rising
      PI-RADS score, values of 4 and 5 increasing the detection of clinically
      significant tumors and leading to a higher histological stage after RP.

PMID- 26293119
TI  - Charge trapping and de-trapping in isolated CdSe/ZnS nanocrystals under an
      external electric field: indirect evidence for a permanent dipole moment.
AB  - Single nanoparticle studies of charge trapping and de-trapping in core/shell
      CdSe/ZnS nanocrystals incorporated into an insulating matrix and subjected to an
      external electric field demonstrate the ability to reversibly modulate the
      exciton dynamics and photoluminescence blinking while providing indirect evidence
      for the existence of a permanent ground state dipole moment in such nanocrystals.
      A model assuming the presence of energetically deep charge traps physically
      aligned along the direction of the permanent dipole is proposed in order to
      explain the dynamics of nanocrystal blinking in the presence of a permanent
      dipole moment. 

PMID- 26293120
TI  - Non-fecalith-induced appendicitis: etiology, imaging, and pathology.
AB  - This study aims to document the imaging and pathology findings in non-fecalith
      induced appendicitis. We reviewed the imaging and pathologic findings in 40
      patients with histologically proven purulent appendicitis seen over a 2-year
      period. Findings documented were (1) total appendiceal involvement, (2)
      predominant appendiceal tip involvement, (3) presence of a fecalith, and (4)
      presence of lymphoid hyperplasia. There were a total of 40 patients, 28 males and
      12 females. The age range was 2-18 years with a mean of 11.5 years. Twenty-two
      (55 %) patients demonstrated classic purulent appendicitis of the whole appendix,
      20 (91 %) of these appendices had a fecalith. Eighteen (45 %) patients
      demonstrated purulent appendicitis confined to or predominately involving the tip
      of the appendix, and all 18 (100 %) patients demonstrated marked lymphoid
      hyperplasia. Only two (11 %) of these appendices had a fecalith. Overall, a
      fecalith was found in only 55 % of our cases, while 45 % demonstrated no
      fecalith, but rather marked lymphoid hyperplasia. Lymphoid hyperplasia appeared
      to be the underlying predisposing cause of purulent appendicitis in these cases.

PMID- 26293121
TI  - High-frequency hearing, tinnitus, and patient satisfaction with stapedotomy: A
      randomized prospective study.
AB  - Otosclerosis is a common disorder that leads to conductive hearing loss. Most
      patients with otosclerosis also have tinnitus, and surgical treatment is known to
      improve hearing as well as tinnitus. Some patients however experience worsening
      of tinnitus after the operation, but there are no known factors that allow
      surgeons to predict who will be at risk. In this prospective observational study
      on 133 patients undergoing stapedotomy, we show that postoperative air conduction
      thresholds at very high stimulus frequencies predict improvement of tinnitus, as
      assessed with proportional odds logistic regression models. Young patients were
      significantly more likely to experience reduction of tinnitus and patients whose
      tinnitus became better were also more satisfied with the outcome of the
      operation. These findings have practical importance for patients and their
      surgeons. Young patients can be advised that surgery is likely to be beneficial
      for their tinnitus, but a less positive message should be conveyed to older
      patients. 

PMID- 26293122
TI  - Etiopathogenesis of Basedow's disease. Trends and current aspects.
AB  - Basedow's disease (BD) owes its name to the German physician Karl Adolph von
      Basedow, who described in 1840 the clinical picture of exophthalmic toxic goitre.
      More than one century after the seminal paper of Karl von Basedow, the ultimate
      cause of BD remains to be fully elucidated. In the last years, evidence was
      accumulated indicating that BD is a polygenic and multifactorial disease that
      develops as a result of a complex interplay between genetic susceptibility and
      environmental and endogenous factors, which leads to the loss of immune tolerance
      to thyroid antigens and in particular to the TSH receptor. Our aim is to review
      the current knowledge on the pathogenesis of BD. To this purpose, we will firstly
      focus our attention on the role of genetic factors (the HLA complex, the genes
      encoding for thyroglobulin, the TSH receptor, CD40, CTLA-4 and PTPN22), and of
      environmental factors (iodine, infections, psychological stress, gender, smoking,
      thyroid damage, vitamin D, selenium, immune modulating agents) as possible causes
      of BD. Taking advantage of the experimental animal models of BD, we will then
      focus on the immunological mechanisms leading to the loss of tolerance in BD. The
      pathogenic role played by the chemokine system will be also reviewed. 

PMID- 26293125
TI  - India health minister lists measures to meet nation's need for doctors.

PMID- 26293123
TI  - Human neural stem cells alleviate Alzheimer-like pathology in a mouse model.
AB  - BACKGROUND: Alzheimer's disease (AD) is an inexorable neurodegenerative disease
      that commonly occurs in the elderly. The cognitive impairment caused by AD is
      associated with abnormal accumulation of amyloid-beta (Abeta) and
      hyperphosphorylated tau, which are accompanied by inflammation. Neural stem cells
      (NSCs) are self-renewing, multipotential cells that differentiate into distinct
      neural cells. When transplanted into a diseased brain, NSCs repair and replace
      injured tissues after migration toward and engraftment within lesions. We
      investigated the therapeutic effects in an AD mouse model of human NSCs (hNSCs)
      that derived from an aborted human fetal telencephalon at 13 weeks of gestation.
      Cells were transplanted into the cerebral lateral ventricles of neuron-specific
      enolase promoter-controlled APPsw-expressing (NSE/APPsw) transgenic mice at 13
      months of age. RESULTS: Implanted cells extensively migrated and engrafted, and
      some differentiated into neuronal and glial cells, although most hNSCs remained
      immature. The hNSC transplantation improved spatial memory in these mice, which
      also showed decreased tau phosphorylation and Abeta42 levels and attenuated
      microgliosis and astrogliosis. The hNSC transplantation reduced tau
      phosphorylation via Trk-dependent Akt/GSK3beta signaling, down-regulated Abeta
      production through an Akt/GSK3beta signaling-mediated decrease in BACE1, and
      decreased expression of inflammatory mediators through deactivation of microglia
      that was mediated by cell-to-cell contact, secretion of anti-inflammatory factors
      generated from hNSCs, or both. The hNSC transplantation also facilitated synaptic
      plasticity and anti-apoptotic function via trophic supplies. Furthermore, the
      safety and feasibility of hNSC transplantation are supported. CONCLUSIONS: These
      findings demonstrate the hNSC transplantation modulates diverse AD pathologies
      and rescue impaired memory via multiple mechanisms in an AD model. Thus, our data
      provide tangible preclinical evidence that human NSC transplantation could be a
      safe and versatile approach for treating AD patients.

PMID- 26293124
TI  - The training and detraining effect of high-intensity interval training on post
      exercise hypotension in young overweight/obese women.
AB  - PURPOSE: Studies evaluating the response in blood pressure (BP) following high
      intensity interval training (HIIT) are scant even though there has been extensive
      work done on the BP response following acute and chronic low- to moderate
      intensity aerobic and resistance exercise in both hypertensive and normotensive
      individuals. The present study sought to investigate the training and detraining
      effects of short-term HIIT on the post-exercise hypotension (PEH) response in
      overweight/obese young women. METHOD: Twenty young untrained women volunteered
      for the study. Participants performed six HIIT sessions on a treadmill within 2
      weeks (week 1: 10 * 1 min and week 2: 15 * 1 min intervals at 90-95% HRmax,
      separated by 1 min active recovery at 70% HRmax each session) and detrained for 2
      weeks. Post-exercise BP was measured for 1 h following the first and last HIIT
      sessions. RESULTS: Participants were normotensive (SBP: 119.2 +/- 5.60 mmHg; DBP:
      78.8 +/- 4.12 mmHg) and had a BMI greater than 25 kg m(-2). The magnitude of the
      systolic hypotensive response was slightly greater after the six sessions HIIT
      compared to pre-training (5.04 and 4.28 mmHg, respectively), and both would be
      considered clinically significant (>3 mmHg decrease). After 2 weeks, detraining
      the PEH response was not clinically significant (1.08 mmHg decrease). The
      magnitude of the DBP response was only clinically significant following post- and
      detraining (4.26 and 3.87 mmHg, respectively). CONCLUSION: The findings suggest
      that six HIIT sessions is sufficient to affect clinically significant PEH
      responses in young, overweight/obese women; however, the training effects are
      lost within 2 weeks of detraining.

PMID- 26293126
TI  - Stable isotope labeling strategy based on coding theory.
AB  - We describe a strategy for stable isotope-aided protein nuclear magnetic
      resonance (NMR) analysis, called stable isotope encoding. The basic idea of this
      strategy is that amino-acid selective labeling can be considered as "encoding and
      decoding" processes, in which the information of amino acid type is encoded by
      the stable isotope labeling ratio of the corresponding residue and it is decoded
      by analyzing NMR spectra. According to the idea, the strategy can diminish the
      required number of labelled samples by increasing information content per sample,
      enabling discrimination of 19 kinds of non-proline amino acids with only three
      labeled samples. The idea also enables this strategy to combine with information
      technologies, such as error detection by check digit, to improve the robustness
      of analyses with low quality data. Stable isotope encoding will facilitate NMR
      analyses of proteins under non-ideal conditions, such as those in large complex
      systems, with low-solubility, and in living cells. 

PMID- 26293127
TI  - GLP-1 receptor agonists in type 1 diabetes: a proof-of-concept approach.
AB  - AIMS: To test potential efficacy of liraglutide, a GLP-1 receptor agonist, in
      subjects with type 1 diabetes (T1DM). METHODS: We have recruited nine T1DM
      patients (age 40.1 +/- 6.4 years, duration of diabetes 19.2 +/- 8.8 years, BMI
      24.3 +/- 3.5 kg/m(2), HbA1c 8.2 +/- 1.0 %-66 +/- 11 mmol/mol, daily insulin dose:
      0.6 +/- 0.1 IU/kg) on continuous subcutaneous insulin therapy with undetectable C
      peptide. In addition to existing treatment was administered in single-blind (a)
      therapy subcutaneously with 0.1 ml of saline solution for 3 days and (b) 0.1 ml
      of liraglutide (0.6 mg/day) for a further 3 days with daily glucose excursions
      recorded by continuous glucose monitoring. RESULTS: Adding liraglutide resulted
      in a significant reduction in mean blood glucose (138 +/- 29 vs. 163 +/- 29
      mg/dl, p < 0.0001) and standard deviation (42 +/- 9 vs. 60 +/- 15 mg/dl, p <
      0.0001). The area under the curve (AUC) for blood glucose >140 mg/dl was also
      significantly reduced (22.2 +/- 16.4 vs. 41.1 +/- 19.7 mg/dl h, p < 0.05) with no
      difference in AUC for blood glucose <70 mg/dl (liraglutide 0.7 +/- 0.9 mg/dl h;
      placebo: 0.8 +/- 1.4 mg/dl h, p = NS). Finally, adding liraglutide reduced daily
      insulin requirement (37.5 +/- 17.2 vs. 42.9 +/- 22.4 UI/day, p < 0.01).
      CONCLUSIONS: Short-term treatment with liraglutide, in T1DM, reduces average
      blood glucose, blood glucose variability and daily insulin requirement without
      increasing risk of hypoglycemia.

PMID- 26293128
TI  - Contrast-enhanced angiographic cone-beam computed tomography without pre-diluted
      contrast medium.
AB  - INTRODUCTION: Contrast-enhanced cone-beam computed tomography (CBCT) has been
      introduced and accepted as a useful technique to evaluate delicate vascular
      anatomy and neurovascular stents. Current protocol for CBCT requires quantitative
      dilution of contrast medium to obtain adequate quality images. Here, we introduce
      simple methods to obtain contrast-enhanced CBCT without quantitative contrast
      dilution. METHODS: A simple experiment was performed to estimate the change in
      flow rate in the internal carotid artery during the procedure. Transcranial
      doppler (TCD) was used to evaluate the velocity change before and after
      catheterization and fluid infusion. In addition, 0.3 cm(3)/s (n = 3) and 0.2
      cm(3)/s (n = 7) contrast infusions were injected and followed by saline flushes
      using a 300 mmHg pressure bag to evaluate neurovascular stent and host arteries.
      RESULTS: Flow velocities changed -15 +/- 6.8 % and +17 +/- 5.5 % from baseline
      during catheterization and guiding catheter flushing with a 300 mmHg pressure
      bag, respectively. Evaluation of the stents and vascular structure was feasible
      using this technique in all patients. Quality assessment showed that the 0.2
      cm(3)/s contrast infusion protocol was better for evaluating the stent and host
      artery. CONCLUSION: Contrast-enhanced CBCT can be performed without quantitative
      contrast dilution. Adequate contrast dilution can be achieved with a small saline
      flush and normal blood flow.

PMID- 26293129
TI  - Alterations in white matter volume and its correlation with clinical
      characteristics in patients with generalized anxiety disorder.
AB  - INTRODUCTION: Only a few morphological studies have focused on changes in white
      matter (WM) volume in patients with generalized anxiety disorder (GAD). We
      evaluated alterations in WM volume and its correlation with symptom severity and
      duration of illness in adults with GAD. METHODS: The 44 subjects were comprised
      of 22 patients with GAD (13 males and nine females) diagnosed using the
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text
      Revision (DSM-IV-TR) and 22 age-matched healthy controls (13 males and nine
      females). High-resolution magnetic resonance imaging (MRI) data were processed by
      voxel-based morphometry (VBM) analysis based on diffeomorphic anatomical
      registration using the exponentiated Lie algebra (DARTEL) algorithm in SPM8.
      RESULTS: Patients with GAD showed significantly reduced WM volume, particularly
      in the dorsolateral prefrontal cortex (DLPFC), anterior limb of the internal
      capsule (ALIC), and midbrain. In addition, DLPFC volume was negatively correlated
      with GAD-7 score and illness duration. ALIC volume was negatively correlated with
      GAD-7 score. Female patients had significantly less orbitofrontal cortex volume
      compared to that in male patients. CONCLUSION: The findings demonstrate localized
      changes in WM volume associated with cognitive and emotional dysfunction in
      patients with GAD. The finding will be helpful for understanding the
      neuropathology in patients with GAD.

PMID- 26293131
TI  - Honor Killing: Where Pride Defeats Reason.
AB  - Honor killings are graceless and ferocious murders by chauvinists with an
      antediluvian mind. These are categorized separately because these killings are
      committed for the prime reason of satisfying the ego of the people whom the
      victim trusts and always looks up to for support and protection. It is for this
      sole reason that honor killings demand strict and stern punishment, not only for
      the person who committed the murder but also for any person who contributed or
      was party to the act. A positive change can occur with stricter legislation and
      changes in the ethos of the society we live in today.

PMID- 26293130
TI  - Supratentorial white matter blurring associated with voltage-gated potassium
      channel-complex limbic encephalitis.
AB  - INTRODUCTION: Limbic encephalitis (LE) associated with voltage-gated potassium
      channel-complex antibodies (VGKC-LE) is frequently non-paraneoplastic and
      associated with marked improvement following corticosteroid therapy. Mesial
      temporal lobe abnormalities are present in around 80 % of patients. If associated
      or preceded by faciobrachial dystonic seizures, basal ganglia signal changes may
      occur. In some patients, blurring of the supratentorial white matter on T2
      weighted images (SWMB) may be seen. The purpose of this study was to evaluate the
      incidence of SWMB and whether it is specific for VGKC-LE. METHODS: Two
      experienced neuroradiologists independently evaluated signal abnormalities on
      FLAIR MRI in 79 patients with LE while unaware on the antibody type. RESULTS:
      SWMB was independently assessed as present in 10 of 36 (28 %) compared to 2 (5 %)
      of 43 non-VGKC patients (p = 0.009). It was not related to the presence of LGI1
      or CASPR2 proteins of VGKC antibodies. MRI showed increased temporomesial FLAIR
      signal in 22 (61 %) VGKC compared to 14 (33 %) non-VGKC patients (p = 0.013), and
      extratemporomesial structures were affected in one VGKC (3 %) compared to 11 (26
      %) non-VGKC patients (p = 0.005). CONCLUSION: SWMB is a newly described MRI sign
      rather specific for VGKC-LE.

PMID- 26293132
TI  - Intrapancreatic bile duct metastasis from colon cancer after resection of liver
      metastasis with intrabiliary growth: a case report.
AB  - An extremely rare case of intrapancreatic bile duct metastasis from sigmoid colon
      adenocarcinoma is herein presented. Sigmoid colon cancer (T3, N0, M0, stage IIA)
      had been diagnosed and treated by sigmoidectomy in October 1993. In December
      2002, a liver metastasis with intrabiliary growth was found, and this was treated
      by extended right hepatic lobectomy and caudate lobectomy with extrahepatic bile
      duct resection. In February 2014, intrapancreatic bile duct metastasis was found,
      and this was treated by subtotal stomach-preserving pancreatoduodenectomy. The
      intrapancreatic metastasis was judged to have arisen from cancer cell
      implantation, either by spontaneous shedding of cancer cells or as a complication
      of percutaneous transhepatic biliary drainage. Twelve months have passed since
      the last surgical intervention, and there has been no sign of local recurrence or
      distant metastasis. Differential diagnosis between intrahepatic
      cholangiocarcinoma and intrabiliary growth of a liver metastasis originating from
      colorectal adenocarcinoma is difficult but very important for determining the
      therapeutic strategy. Careful examination is needed to diagnose intrahepatic
      biliary dilatation, especially for patients with a history of carcinoma in the
      digestive tract and even if years have passed since curative resection of the
      digestive tract cancer. Aggressive surgical management for localized recurrence
      of a hepatic metastasis from colorectal adenocarcinoma may improve patient
      survival. 

PMID- 26293134
TI  - All-solid-state lithium-oxygen battery with high safety in wide ambient
      temperature range.
AB  - There is need to develop high energy storage devices with high safety to satisfy
      the growing industrial demands. Here, we show the potential to realize such
      batteries by assembling a lithium-oxygen cell using an inorganic solid
      electrolyte without any flammable liquid or polymer materials. The lithium-oxygen
      battery using Li1.575Al0.5Ge1.5(PO4)3 solid electrolyte was examined in the pure
      oxygen atmosphere from room temperature to 120  degrees C. The cell works at room
      temperature and first full discharge capacity of 1420 mAh g(-1) at 10 mA g(-1)
      (based on the mass of carbon material in the air electrode) was obtained. The
      charge curve started from 3.0 V, and that the majority of it lay below 4.2 V. The
      cell also safely works at high temperature over 80  degrees C with the improved
      battery performance. Furthermore, fundamental data of the electrochemical
      performance, such as cyclic voltammogram, cycle performance and rate performance
      was obtained and this work demonstrated the potential of the all-solid-state
      lithium-oxygen battery for wide temperature application as a first step. 

PMID- 26293133
TI  - Regional and global forcing of glacier retreat during the last deglaciation.
AB  - The ongoing retreat of glaciers globally is one of the clearest manifestations of
      recent global warming associated with rising greenhouse gas concentrations. By
      comparison, the importance of greenhouse gases in driving glacier retreat during
      the most recent deglaciation, the last major interval of global warming, is
      unclear due to uncertainties in the timing of retreat around the world. Here we
      use recently improved cosmogenic-nuclide production-rate calibrations to
      recalculate the ages of 1,116 glacial boulders from 195 moraines that provide
      broad coverage of retreat in mid-to-low-latitude regions. This revised history,
      in conjunction with transient climate model simulations, suggests that while
      several regional-scale forcings, including insolation, ice sheets and ocean
      circulation, modulated glacier responses regionally, they are unable to account
      for global-scale retreat, which is most likely related to increasing greenhouse
      gas concentrations. 

PMID- 26293135
TI  - Principle and Performance of Gas Self-inducing Reactors and Applications to
      Biotechnology.
AB  - Gas-liquid contacting is an important unit operation in chemical and biochemical
      processes, but the gas utilization efficiency is low in conventional gas-liquid
      contactors especially for sparingly soluble gases. The gas self-inducing impeller
      is able to recycle gas in the headspace of a reactor to the liquid without
      utilization of additional equipment such as a gas compressor, and thus, the gas
      utilization efficiency is significantly enhanced. Gas induction is caused by the
      low pressure or deep vortex at a sufficiently high impeller speed, and the speed
      at which gas induction starts is termed the critical speed. The critical impeller
      speed, gas-induction flow rate, power consumption, and gas-liquid mass transfer
      are determined by the impeller design and operation conditions. When the reactor
      is operated in a dead-end mode, all the introduced gas can be completely used,
      and this feature is especially favorable to flammable and/or toxic gases. In this
      article, the principles, designs, characteristics of self-inducing reactors, and
      applications to biotechnology are described.

PMID- 26293136
TI  - Country characteristics and acute diarrhea in children from developing nations: a
      multilevel study.
AB  - BACKGROUND: Each year 2.5 billion cases of diarrheal disease are reported in
      children under five years, and over 1,000 die. Country characteristics could play
      a role on this situation. We explored associations between country
      characteristics and diarrheal disease in children under 5 years of age, adjusting
      by child, mother and household attributes in developing countries. METHODS: This
      study included 348,706 children from 40 nations. We conducted a multilevel
      analysis of data from the Demographic and Health Surveys and the World Bank.
      RESULTS: The prevalence of acute diarrhea was 14 %. Country inequalities (OR =
      1.335; 95 % CI 1.117-1.663) and country's low income (OR = 1.488; 95 % CI 1.024
      2.163) were associated with diarrhea, and these country characteristics changed
      the associations of well-known determinants of diarrhea. Specifically, living in
      poor countries strengthens the association of poor household wealth and mother's
      lack of education with the disease. Other factors associated with diarrhea were
      female sex of the child (OR = 0.922; 95 % CI 0.900-0.944), age of the child (OR =
      0.978; 95 % CI 0.978-0.979), immunization status (OR = 0.821; 95 % CI 0.799
      0.843), normal birthweight (OR = 0.879; 95 % CI 0.834-0.926), maternal age (OR =
      0.987; 95 % CI 0.985-0.989), lack of maternal education (OR = 1.416; 95 % CI
      1.283-1.564), working status of the mother (OR = 1.136; 95 % CI 1.106-1.167),
      planned pregnancy (OR = 0.774; 95 % CI 0.753-0.795), a nuclear family structure
      (OR = 0.949; 95 % CI 0.923-0.975), and household wealth (OR = 0.948; 95 % CI
      0.921-0.977). CONCLUSIONS: Inequalities and lack of resources at the country
      level in developing countries -but not health expenditure- were associated with
      acute diarrhea, independently of child, family and household features. The broad
      environment considerably modifies well-known social determinants of acute
      diarrhea and public health campaigns designed to target diarrhea should consider
      macro characteristics of the country.

PMID- 26293137
TI  - Geographic distribution of HCV genotypes in Libya and analysis of risk factors
      involved in their transmission.
AB  - BACKGROUND: Hepatitis C virus (HCV) genotypes have been shown to be differently
      distributed between distinct geographical areas. Libya is a large country has the
      longest coast in the Mediterranean basin. Information regarding hepatitis C
      genotypes and subtypes circulating in Libya are not well known. The objectives of
      this study were to determine the frequency of various HCV genotypes cross Libya
      and the demographic and attributable risk factors associated with HCV
      transmission among Libyan population. METHODS: A cross-sectional study was
      carried out on patients with recently confirmed HCV infection. A total of 3,227
      serum samples enrolled at 19 collection center cross Libya. 1,756 belonged to
      Tripoli region, 452 to West region 355 to North region, 181 South regions and 483
      East region. The samples were tested by type specific genotyping assay and
      correlated with demographic and potential risk factors within the studied
      populations. RESULTS: A total of 20 discrete genotypes and subtypes were
      identified among the Libyan population ranging from 11.5 to 0.3% cross the
      country. Genotype 1 was the most frequent among all regions (19.7-40.5%),
      reaching the highest value in Tripoli region, followed by genotype 4 which was
      more prevalent in the South (49.3%) and West (40.0%) regions. Genotype 3, was
      higher in Tripoli (21.3%) and East (15.9%) regions while genotype 2, common in
      North (23.6%) and South (22.5%) regions. However, we found evidence that there is
      a changing relative prevalence of HCV genotypes in relation to age, gender and
      the mode of transmission which is reflected in the predominance of certain
      genotypes among Libyan population. CONCLUSIONS: Different HCV genotypes were
      isolated form Libyan population including newly emerged ones. The prevalence of
      the genotypes varied by geographic region and influenced by demographic and risk
      factors. Knowing the frequency and distribution of the genotypes would provide
      key information on understanding the spread of HCV in Libya and this could be
      greatly reflected on national plans and future strategies for infection
      prevention.

PMID- 26293139
TI  - Peripheral lamina cribrosa depth in primary open-angle glaucoma: a swept-source
      optical coherence tomography study of lamina cribrosa.
AB  - PURPOSE: To investigate peripheral lamina cribrosa depth (PLCD) and its vertical
      horizontal difference in eyes with primary open-angle glaucoma (POAG). METHODS:
      Patients with POAG (n=90 eyes) and age-matched healthy individuals (n=90 eyes)
      underwent swept-source optical coherence tomography (SS-OCT) scans centered at
      the optic discs. The PLCD was defined as the vertical distance between the most
      peripheral visible end of anterior lamina cribrosa (LC) surface and the reference
      plane connecting the Bruch's membrane openings. The PLCD in each quadrant region
      and the vertical-horizontal PLCD difference were compared between the POAG and
      healthy eyes. The clinical factors associated with increased PLCD were evaluated.
      RESULTS: The PLCD was significantly larger in the POAG eyes than the control eyes
      at the horizontal (P=0.034) and vertical (P=0.001) meridians. The vertical PLCD
      was significantly larger than the horizontal PLCD, both in the POAG eyes
      (P<0.001) and in the control eyes (P=0.003). However, the vertical-horizontal
      PLCD difference was significantly larger in the POAG eyes (47+/-60 MUm) than in
      the control eyes (18+/-54 MUm, P=0.001). Multivariate regression showed a
      significant association of male gender (P=0.005), increased baseline IOP
      (P=0.043), and decreased MD of VF (P=0.025) with increased PLCD. CONCLUSIONS: The
      peripheral LC was displaced more posteriorly in the POAG eyes compared with the
      age-matched healthy eyes. In the POAG eyes, the peripheral LC was displaced more
      posteriorly at the vertical meridian than at the horizontal meridian. The
      peripheral LC in the vertical meridian might have increased IOP-related strain
      (deformation) compared with horizontal meridian in glaucomatous eyes.

PMID- 26293138
TI  - Advances in retinal ganglion cell imaging.
AB  - Glaucoma is one of the leading causes of blindness worldwide and will affect 79.6
      million people worldwide by 2020. It is caused by the progressive loss of retinal
      ganglion cells (RGCs), predominantly via apoptosis, within the retinal nerve
      fibre layer and the corresponding loss of axons of the optic nerve head. One of
      its most devastating features is its late diagnosis and the resulting
      irreversible visual loss that is often predictable. Current diagnostic tools
      require significant RGC or functional visual field loss before the threshold for
      detection of glaucoma may be reached. To propel the efficacy of therapeutics in
      glaucoma, an earlier diagnostic tool is required. Recent advances in retinal
      imaging, including optical coherence tomography, confocal scanning laser
      ophthalmoscopy, and adaptive optics, have propelled both glaucoma research and
      clinical diagnostics and therapeutics. However, an ideal imaging technique to
      diagnose and monitor glaucoma would image RGCs non-invasively with high
      specificity and sensitivity in vivo. It may confirm the presence of healthy RGCs,
      such as in transgenic models or retrograde labelling, or detect subtle changes in
      the number of unhealthy or apoptotic RGCs, such as detection of apoptosing
      retinal cells (DARC). Although many of these advances have not yet been
      introduced to the clinical arena, their successes in animal studies are
      enthralling. This review will illustrate the challenges of imaging RGCs, the main
      retinal imaging modalities, the in vivo techniques to augment these as specific
      RGC-imaging tools and their potential for translation to the glaucoma clinic. 

PMID- 26293140
TI  - Hyperopic refractive errors as a prognostic factor in intermittent exotropia
      surgery.
AB  - Purpose: To evaluate and compare surgical outcomes with respect to refractive
      errors in strabismus surgery for the treatment of intermittent exotropia (IXT).
      METHODS: The medical records of patients with IXT who were treated by one surgeon
      from January 2005 and June 2011 were reviewed. Three hundred and thirty-three IXT
      patients were included and divided into three groups according to preoperative
      refractive error: IXT with hyperopia (group I), IXT with emmetropia (group II),
      and IXT with myopia (group III). The surgical outcomes with respect to sensory
      and motor criteria were compared among the three groups. RESULTS: The surgical
      success rates according to motor criteria and sensory and motor criteria combined
      were higher in groups I (29 patients) and III (124 patients) than in group II
      (180 patients) at postoperative 3 and 6 months and at the last follow-up.
      Stereopsis was significantly better in groups II and III than in group I
      preoperatively (P=0.002 by one-way analysis of variance test); however, the
      difference was not significant postoperatively. Twenty patients in group I
      (69.0%) were prescribed undercorrected hyperopic spectacles postoperatively,
      while only 22 patients in group III (17.7%) were prescribed spectacles with more
      myopic power than their refractive errors. CONCLUSION: In the surgical treatment
      of IXT, hyperopia was not an indicator of poor prognosis. Taking into
      consideration the age effect, follow-up period after IXT surgery, and stereopsis
      improvement, hyperopic refractive error is rather a good prognostic factor.

PMID- 26293141
TI  - Blepharitis: remains a diagnostic enigma. A role for tea tree oil shampoo?

PMID- 26293143
TI  - The accuracy of the Edinburgh visual loss diagnostic algorithm.
AB  - PURPOSE: To assess the diagnostic accuracy of the Edinburgh visual loss
      algorithm. METHODS: This was a prospective study. Patients referred to the
      Edinburgh Eye Pavilion with visual loss were assessed using the Edinburgh Visual
      Loss Algorithm by either a medical student, an inexperienced ophthalmology
      trainee or an optometrist in the Lothian Optometry Treat and Teach clinic.
      Accuracy of this 'algorithm-assisted' diagnosis was then compared with the 'gold
      standard' diagnosis, made by an experienced ophthalmologist. Accuracy of the pre
      algorithm diagnosis, made by the referrer, was also compared with the algorithm
      assisted diagnosis. RESULTS: All patients referred with visual loss were eligible
      for inclusion. Seventy patients were assessed; two were excluded. Pre-algorithm
      accuracy of referral of patients with visual loss was 51% (30/59). Overall, the
      algorithm-assisted diagnosis was correct 84% (57/68) of the time. The algorithm
      correctly diagnosed: retina in 71% of cases (5/7), macula in 86% (25/29),
      peripheral retina in 100% (2/2), optic nerve in 71% (5/7), media opacity in 89%
      (16/18), post chiasmal in 100% (4/4), and refractive error in 0% (0/1). Accuracy
      of diagnosis was similar for each algorithm user; medical student 81%,
      inexperienced ophthalmology trainee 84% and optometrist 92%. DISCUSSION: The
      baseline diagnostic accuracy of clinicians who are inexperienced in ophthalmology
      rose from 51 to 84% when patients were assessed using the algorithm. This
      algorithm significantly improves the diagnostic accuracy of referrals to the
      hospital eye service, regardless of the user's previous ophthalmic experience. We
      hope we have demonstrated its potential as a learning tool for inexperienced
      clinicians.

PMID- 26293142
TI  - Periodic acid-Schiff staining demonstrates fungi in chronic anterior blepharitis.
AB  - PURPOSE: To evaluate the presence of fungi in patients with chronic anterior
      blepharitis with periodic acid-Schiff (PAS) staining of the eyelashes in addition
      to the conventional methods of fungal cultures and direct microscopy. METHODS:
      Nineteen patients with chronic anterior blepharitis of seborrheic or mixed
      seborrheic/staphylococcal type and 11 healthy age- and sex-matched controls were
      included in this prospective, nonrandomized, cross-sectional study. Blepharitis
      was diagnosed based on clinical evidence of greasy scales between the cilia, lid
      margin erythema, conjunctival hyperemia, telangiectasia, thickening, or
      irregularity of the eyelid margins by slit-lamp biomicroscopy. Eyelash samples
      were obtained by epilation with a sterile forceps and evaluated with PAS
      staining, fungal cultures, and direct microscopy. RESULTS: We demonstrated fungal
      elements with PAS staining in 79% of the blepharitis group (hyphae and/or spores)
      and 18% of the control group. The difference was statistically significant
      (P=0.002). Four patients in the blepharitis group (21%) had positive cultures for
      fungi. The isolated fungi were Penicillium species (2 cases), Candida species (1
      case), and Trichophyton verrucosum (1 case). Direct microscopic examination
      revealed Demodex mites in 42.1% of the blepharitis group. No culture growth or
      Demodex mites were observed in the control group. CONCLUSIONS: We have shown
      fungi with PAS staining in the majority of patients with chronic anterior
      blepharitis. Further controlled studies are necessary to clarify the role of
      fungi in the etiopathogenesis of blepharitis.

PMID- 26293144
TI  - Utilizing the concept of geste antagoniste for conservative management of oro
      mandibular tardive dyskinesia: a case report and mini-review.
AB  - OBJECTIVE: This case report highlights the implication of the concept of "geste
      antagoniste" in conservatively managing oromotor dysfunction and its
      complications. CLINICAL PRESENTATION: A 66-year-old female with a 1-year history
      of tardive dyskinesia (TD) was referred to the Craniofacial Pain Department (CPC)
      at Tufts University School of Dental Medicine for management of sore
      labial/lingual mucosa secondary to excessive daytime involuntary activity of the
      tongue, lips, and mandible. A detailed head/neck examination revealed excessive
      involuntary movements of the tongue, lips, and mandible with generalized
      tenderness of her masticatory muscles. No TMJ or bone pathology was evident in a
      panoramic radiograph. INTERVENTION: A lower daytime appliance with bilateral
      posterior contacts was fabricated to protect her oral mucosa. On reevaluation,
      excessive movement of the jaw/tongue was significantly reduced with the presence
      of the appliance in her mouth. Face/neck muscle tenderness was also greatly
      reduced. CONCLUSION: The use of oral appliance therapy in TD patients plays an
      important role in protecting the teeth/oral mucosa. The subsequent inhibition of
      excessive motor activity is proposed and should be further investigated.

PMID- 26293145
TI  - Smart Fiber Membrane for pH-Induced Oil/Water Separation.
AB  - Wastewater contaminated with oil or organic compounds poses threats to the
      environment and humans. Efficient separation of oil and water are highly desired
      yet still challenging. This paper reports the fabrication of a smart fiber
      membrane by depositing pH-responsive copolymer fibers on a stainless steel mesh
      through electrospinning. The cost-effective precursor material poly(methyl
      methacrylate)-block-poly(4-vinylpyridine) (PMMA-b-P4VP) was synthesized using
      copper(0)-mediated reversible-deactivation radical polymerization. The pH
      responsive P4VP and the underwater oleophilic/hydrophilic PMMA confer the as
      prepared membrane with switchable surface wettability toward water and oil. The
      three-dimensional network structure of the fibers considerably strengthens the
      oil/water wetting property of the membrane, which is highly desirable in the
      separation of oil and water mixtures. The as-prepared fiber membrane accomplishes
      gravity-driven pH-controllable oil/water separations. Oil selectively passes
      through the membrane, whereas water remains at the initial state; after the
      membrane is wetted with acidic water (pH 3), a reverse separation is realized.
      Both separations are highly efficient, and the membrane also exhibits switchable
      wettability after numerous cycles of the separation process. This cost-effective
      and easily mass-produced smart fiber membrane with excellent oil-fouling
      repellency has significant potential in practical applications, such as water
      purification and oil recovery. 

PMID- 26293146
TI  - Metformin intervention in obese non-diabetic patients with breast cancer: phase
      II randomized, double-blind, placebo-controlled trial.
AB  - Previous observational studies have suggested that metformin in diabetes patients
      may reduce breast cancer risk more than the reductions from other anti-diabetes
      medications. This randomized, double-blind, placebo-controlled trial was
      performed to evaluate the efficacy of metformin for controlling physical and
      metabolic profiles related to prognosis and adverse events in non-diabetic breast
      cancer patients. Female breast cancer patients (N = 105), at least 6 months post
      mastectomy, with obesity (>=25 kg/m(2)) and/or pre-diabetes (fasting blood sugar
      levels >=100 mg/dL), were randomly assigned to three groups (placebo, metformin
      500 mg, and metformin 1000 mg) stratified by tamoxifen use. A linear mixed model
      for repeated measurements among three groups and ANOVA for profile differences
      during 6 months of treatment were used for the intention-to-treat analysis. The
      metformin 1000 mg group had a significantly greater decline in glucose and HbA1c
      levels between treatment weeks 0 and 6 month (p = 0.008 and 0.009, respectively),
      and the declines increased with an increase in body mass index (BMI) level (p
      interaction with BMI = 0.007 and 0.067, respectively). A marginally significant
      different effect from the metformin 1000 mg treatment was detected for glucose
      and HbA1c levels (p interaction = 0.084 and 0.063, respectively) in the intention
      to-treat analysis. Metformin 1000 mg treatment had a favorable effect on
      controlling glucose and HbA1C levels in obese non-diabetic breast cancer
      patients, indicating prognostic importance. Further trials are needed to
      elucidate the risk-benefit ratio of long-term use of metformin.

PMID- 26293147
TI  - Supervised physical exercise improves VO2max, quality of life, and health in
      early stage breast cancer patients: a randomized controlled trial.
AB  - Breast cancer patients suffer impairment in cardiorespiratory fitness after
      treatment for primary disease, affecting patients' health and survival. The aim
      of this study was to evaluate the ability of a pragmatic exercise intervention to
      improve cardiorespiratory fitness of breast cancer patients after primary
      treatment. Between February 2013 and December 2014, 94 women with early stage (I
      III) breast cancer, 1-36 months post-chemotherapy, and radiotherapy were randomly
      assigned to an intervention program (EX) combining supervised aerobic and
      resistance exercise (n = 44) or usual care (CON) (n = 45) for 12 weeks. Primary
      study endpoint was VO2max. Secondary endpoints were muscle strength, shoulder
      range of motion, body composition, and quality of life (QoL). Assessments were
      undertaken at baseline, 12-week, and 6-month follow-ups. Eighty-nine patients
      aged 29-69 years were assessed at baseline and 12 weeks. The EX group showed
      significant improvements in VO2max, muscle strength, percent fat, and lean mass
      (p <= 0.001 in all cases) and QoL compared with usual care (CON). Apart from body
      composition, improvements were maintained for the EX at 6-month follow-up. There
      were no adverse events during the testing or exercise intervention program. A
      combined exercise intervention produced considerable improvement in
      cardiorespiratory fitness, physical function, and quality of life in breast
      cancer patients previously treated with chemotherapy and radiation therapy.
      Importantly, most of these benefits were maintained 6 months after ceasing the
      supervised exercise intervention.

PMID- 26293148
TI  - Does every emergency department patient need a blood lactate?

PMID- 26293149
TI  - Nothing fishy about this bone.

PMID- 26293150
TI  - Towards evidence-based emergency medicine:best BETs from the Manchester Royal
      Infirmary. BET 1: Do patients with a clinically suspected subsegmental pulmonary
      embolism need anticoagulation therapy?
AB  - A short cut review was carried out to establish whether the incidence of
      recurrent venous thromboembolism and mortality is lower among patients with
      isolated subsegmental pulmonary embolism who are treated with anticoagulant
      therapy compared with those who are not treated with anticoagulant therapy. We
      identified six studies that were directly relevant to the question. All of these
      studies were observational in nature and included only a small number of patients
      with isolated subsegmental pulmonary embolism who were not treated with
      anticoagulants. Of those studies, only two included patients with confirmed
      isolated subsegmental pulmonary embolism that were not treated with
      anticoagulation. Among the 47 patients meeting those criteria, no recurrent
      venous thromboembolism was noted within 3 months. The author, date and country of
      publication, patient group studied, study type, relevant outcomes, results and
      study weaknesses of these papers are tabulated. The clinical bottom line is that
      the limited available evidence suggests that the incident of recurrent venous
      thromboembolism is very low in patients with isolated subsegmental pulmonary
      embolism. However, this is based on limited data from small observational
      studies. Further evidence from larger trials is necessary before a recommendation
      can be made to withhold anticoagulation in this situation. 

PMID- 26293152
TI  - Towards evidence-based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 2: The use of age-related D-dimers to rule out deep vein
      thrombosis.
AB  - A short cut review was carried out to establish whether the use of age-adjusted D
      dimer cut-offs is better than the standard, unadjusted diagnostic cut-off for
      excluding the diagnosis of deep vein thrombosis (DVT) in the Emergency
      Department. Three studies were directly relevant to the question. The author,
      date and country of publication, patient group studied, study type, relevant
      outcomes, results and study weaknesses of these papers are tabulated. The
      clinical bottom line is that the use of an age-adjusted D-dimer cut-off in
      patients aged over 50 years increases the ability to safely exclude DVT in
      patients with low clinical probability without the need for ultrasound scanning.

PMID- 26293154
TI  - Purification and Characterization of Nk-3FTx: A Three Finger Toxin from the Venom
      of North East Indian Monocled Cobra.
AB  - Snake venom three finger toxins (3FTxs) are a non-enzymatic family of venom
      proteins abundantly found in elapids. We have purified a 7579.5 +/- 0.591 Da 3FTx
      named as Nk-3FTx from the venom of Naja kaouthia of North East India origin. The
      primary structure was determined by a combination of N-terminal sequencing and
      electrospray ionization liquid chromatography-mass spectrometry/mass
      spectrometry. Biochemical and biological characterization reveal that it is
      nontoxic to human cell lines and exhibit mild anticoagulant activity when tested
      on citrated human plasma. Nk-3FTx was found to affect the compound action
      potential (CAP) and nerve conduction velocity of isolated toad sciatic nerve.
      This is the first report of a non-conventional 3FTx from Naja kaouthia venom that
      reduces CAP for its neurotoxic effect. Further studies can be carried out to
      understand the mechanism of action and to explore its potential therapeutic
      application.

PMID- 26293153
TI  - Optimizing senior's surgical care - Elder-friendly Approaches to the Surgical
      Environment (EASE) study: rationale and objectives.
AB  - BACKGROUND: It is estimated that seniors (>=65 years old) account for >50% of
      acute inpatient hospital days and are presenting for surgical evaluation of acute
      illness in increasing numbers. Unfortunately, conventional acute care models
      rarely take into account needs of the elderly population. The failure to consider
      these special needs have resulted in poor outcomes, longer lengths of hospital
      stay and have likely increased the need for institutional care. Acute Care for
      the Elderly models on medical wards have demonstrated decreased cost, length of
      hospital stay, readmissions and improved cognition, function and patient/staff
      satisfaction. We hypothesize that specific Elder-friendly Approaches to the
      Surgical Environment (EASE) interventions will similarly improve health outcomes
      in a cost-effective manner. METHODS/DESIGN: Prospective, before-after study with
      a concurrent control group. Four cohorts of 140 consecutively-screened older
      patients (>=65 years old) will be enrolled (560 patients in total). The EASE
      interventions involves co-locating all older surgical patients on a single unit,
      involving an interdisciplinary care team (including a geriatric specialist) in
      the development of individual care plans, implementing evidence-informed elder
      friendly practices, use of a reconditioning program, and optimizing discharge
      planning. Subjects will be followed via chart review for their hospital stay, and
      will then complete in-person or telephone interviews at 6 weeks and 6 months
      after discharge. Measured outcomes include clinical (postoperative major in
      hospital complication or death [primary composite outcome]; death or readmission
      within 30-days of initial discharge; length of hospital stay), humanistic
      (quality of life; functional, cognitive, and nutritional status) and economic
      (health care resource utilization and costs) endpoints. Within-site mean change
      scores will be computed for the composite primary outcome and the overall
      covariate-adjusted between-site pre-post difference will be the dependent
      variable analyzed using generalized linear mixed model procedures including
      adjustment for clustering. DISCUSSION: Our findings will generate new knowledge
      on outcomes from acute surgical care in older patients and validate a novel elder
      friendly surgical model including assessment of both clinical and economic
      benefits. If effective, we expect the EASE initiatives to be generalizable to
      other surgical centres. TRIAL REGISTRATION: Clinicaltrials.govidentifier:
      NCT02233153.

PMID- 26293155
TI  - Low Bandgap Semiconducting Copolymer Nanoparticles by Suzuki Cross-Coupling
      Polymerization in Alcoholic Dispersed Media.
AB  - The synthesis and formulation of organic semiconductors for the emerging
      technology of organic electronics requires the use of preparative methods and
      solvents being environment friendly. Today most of the active layer materials for
      the organic photovoltaic devices and modules are using chlorinated solvents,
      which are toxic and hazardous. In this work, the synthesis of poly[N-9'
      heptadecanyl-2,7-carbazole-alt-5,5-(4,7-di-2-thienyl-2',1',3'-benzothiadiazole]
      (PCDTBT) in propan-1-ol is presented as the dispersant continuous phase in the
      presence of poly(vinylpyrrolidone) used as stabilizer. Suzuki-Miyaura
      polycondensation of 9-(9-heptadecanyl)-9H-carbazole-2,7-diboronic acid
      bis(pinacol) ester and 4,7-bis(2-bromo-5-thienyl)-2,1,3-benzothiadiazole in
      alcohol dispersion yields colloidally stable nanoparticles of PCDTBT with
      particles size of 330-1300 nm, depending on the stabilizer concentration. Other
      reaction parameters are also discussed such as the amount of base or Pd catalyst.

PMID- 26293156
TI  - Comparison Between Ultrasonography-Guided Popliteal Sciatic Nerve Block and
      Spinal Anesthesia for Hallux Valgus Repair.
AB  - BACKGROUND: We aimed to compare the efficacy, postoperative pain scores, adverse
      effects, additional analgesic requirements, and patient satisfaction scores of
      ultrasonography-guided sciatic nerve block by popliteal approach with spinal
      anesthesia for hallux valgus correction surgery. METHODS: Sixty patients
      scheduled for hallux valgus correction surgery were enrolled in this prospective
      randomized study. Unilateral spinal block was performed on patients in the spinal
      anesthesia group. Popliteal block group patients received popliteal sciatic nerve
      block with guidance by both nerve stimulator and ultrasonography. Durations of
      anesthetic and operative interventions and time until the initiation of surgery
      were recorded for both groups. Pain magnitude of the patients at the 2nd, 4th,
      6th, 12th, and 24th hours following anesthetic interventions were assessed with a
      visual analog scale (VAS). Adverse effects such as postoperative urinary
      retention and postdural puncture headache were recorded. Also, patient
      satisfaction was recorded. Patients were interviewed by phone for anesthetic and
      operative complications at 72 hours postoperatively. RESULTS: Spinal anesthesia
      group patients exhibited hypotension, bradycardia, postdural puncture headache,
      and urinary retention rates of 6.6%, 3.3%, 10%, and 3.3%, respectively. Popliteal
      block group patients showed none of these adverse effects. Moreover, VAS scores
      of the patients at the 2nd, 4th, 6th, and 12th hours were significantly lower (P
      < .001, P = .003, P < .001, P <.001, respectively), postoperative first analgesic
      requirement times were significantly longer (P < .001), and pain satisfaction
      scores were significantly higher (P < .001) in the popliteal block group.
      CONCLUSION: Given the complications related to spinal anesthesia and its
      insufficiency to maintain analgesia postoperatively, we believe the preferred
      anesthetic method should be peripheral nerve blocks for hallux valgus correction
      surgeries. LEVEL OF EVIDENCE: Level I, randomized prospective study.

PMID- 26293157
TI  - Orientation of the Subtalar Joint: Measurement and Reliability Using
      Weightbearing CT Scans.
AB  - BACKGROUND: Up to 60% of patients with an osteoarthritic ankle joint develop
      talar tilt with progression of the osteoarthritic process. The configuration of
      the subtalar joint, in particular the posterior facet, may contribute to the
      development of this wear pattern. Recently, the subtalar vertical angle (SVA) was
      used to describe the posterior facet of the subtalar joint in the frontal plane.
      The aim of this work was to analyze if the orientation of the subtalar joint may
      influence the type of asymmetric ankle osteoarthritis. METHODS: In total, 60
      ankles were retrospectively analyzed including 40 osteoarthritic patients and 20
      healthy controls. The osteoarthritic ankles were divided into 4 groups: varus
      ankle joints with (incongruent) or without (congruent) a tilted talus and valgus
      ankle joints with (incongruent) or without (congruent) a tilted talus. The
      orientation of the subtalar joint was described using the SVA. The SVA was
      determined for every patient using weightbearing CT scans. Additionally, the
      inter- and intraobserver reliability was assessed using intraclass correlation
      coefficients (ICCs). RESULTS: The inter- and intraobserver reliability was
      excellent (ICC > 0.989 and >0.975, respectively). The varus groups (incongruent
      and congruent) had significantly lower SVA values, that is, more varus
      orientation of the subtalar joint than the valgus groups (P < .05). The SVA of
      the control group was between the values of the varus and valgus ankles.
      CONCLUSION: The SVA provided a reliable and consistent method to assess the
      varus/valgus configuration of the posterior facet of the subtalar joint. In our
      cohort, varus osteoarthritis of the ankle joint occurred with varus orientation
      of the subtalar joint whereas in patients with valgus osteoarthritis, valgus
      orientation of the subtalar joint was found. Our data suggest that the subtalar
      joint orientation may be a risk factor for the development of ankle joint
      osteoarthritis. LEVEL OF EVIDENCE: Level III, retrospective case control study.

PMID- 26293159
TI  - Sensitive detection of piperazinyl phenothiazine drugs by field-amplified sample
      stacking in capillary electrophoresis with dispersive liquid-liquid
      microextraction.
AB  - A rapid, simple and sensitive method for the detection of piperazinyl
      phenothiazine drugs using dispersive liquid-liquid microextraction (DLLME)
      combined with field-amplified sample stacking (FASS) in CE was developed.
      Sensitivity parameters that affect the extraction and FASS efficiency, such as
      the type and volume of disperser solvent, extraction time, addition of salt, and
      efficiency of FASS, were investigated and optimized. Note that the conductivity
      ratio between BGE and sample zone was measured to be 2300. Under optimal
      extraction and stacking conditions, the calibration curve, which ranged from 0.3
      to 160 ng/mL, demonstrated good linearity with a correlation coefficient r?
      0.9900. The LODs of prochlorperazine (Pcp), trifluoperazine (Tfp), perphenazine
      (Ppa), and fluphenazine (Fpa) at an S/N of 3 were 0.1, 0.1, 0.07, and 0.08 ng/mL,
      respectively. An approximately 1000-fold to 2500-fold improvement in sensitivity
      was achieved for the four tested analytes compared to conventional CZE without
      DLLME. The recoveries of all phenothiazines in urine and plasma ranged from 85.7
      to 107.6% and 95.6 to 105.4%, respectively. The proposed method was demonstrated
      to be a rapid and convenient method for the determination of four piperazinyl
      phenothiazine drugs in human urine and plasma.

PMID- 26293158
TI  - Inhibition of SCD1 impairs palmitate-derived autophagy at the step of
      autophagosome-lysosome fusion in pancreatic beta-cells.
AB  - Autophagy is indispensable for the proper architecture and flawless functioning
      of pancreatic beta-cells. A growing body of evidence indicates reciprocal
      communication between autophagic pathways, apoptosis, and intracellular lipids.
      The way in which elevated levels of free saturated or unsaturated FAs contribute
      to progressive beta-cell failure remains incompletely understood. Stearoyl-CoA
      desaturase (SCD)1, a key regulatory enzyme in biosynthesis of MUFAs, was shown to
      play an important role in regulation of beta-cell function. Here, we investigated
      whether SCD1 activity is engaged in palmitate-induced pancreatic beta-cell
      autophagy. We found augmented apoptosis and diminished autophagy upon cotreatment
      of INS-1E cells with palmitate and an SCD1 inhibitor. Furthermore, we found that
      additional treatment of the cells with monensin, an inhibitor of autophagy at the
      step of fusion, exacerbates palmitate-induced apoptosis. Accordingly, diminished
      SCD1 activity affected the accumulation, composition, and saturation status of
      cellular membrane phospholipids and neutral lipids. Such an effect was
      accompanied by aberrant endoplasmic reticulum stress, mitochondrial injury, and
      decreases in insulin secretion and cell proliferation. Our data reveal a novel
      mechanism by which the inhibition of SCD1 activity affects autophagosome-lysosome
      fusion because of perturbations in cellular membrane integrity, thus leading to
      an aberrant stress response and beta-cell failure. 

PMID- 26293160
TI  - Searching PubMed for a broad subject area: how effective are palliative care
      clinicians in finding the evidence in their field?
AB  - OBJECTIVES: Health professionals must be able to search competently for evidence
      to support practice. We sought to understand how palliative care clinicians
      construct searches for palliative care literature in PubMed, to quantify search
      efficacy in retrieving a set of relevant articles and to compare performance
      against a Palliative CareSearch Filter (PCSF). METHODS: Included studies from
      palliative care systematic reviews formed a test set. Palliative care clinicians
      (n = 37) completed a search task using PubMed. Individual clinician searches were
      reconstructed in PubMed and combined with the test set to calculate retrieval
      sensitivity. PCSF performance in the test set was also determined. RESULTS: Many
      clinicians struggled to create useful searches. Twelve used a single search term,
      17 narrowed the search inappropriately and 8 confused Boolean operators. The mean
      number of test set citations (n = 663) retrieved was 166 (SD = 188), or 25%
      although 76% of clinicians believed they would find more than 50% of the
      articles. Only 8 participants (22%) achieved this. Correlations between retrieval
      and PubMed confidence (r = 0.13) or frequency of use (r = -0.18) were weak.
      CONCLUSIONS: Many palliative care clinicians search PubMed ineffectively.
      Targeted skills training and PCSF promotion may improve evidence retrieval.

PMID- 26293162
TI  - Response to: 'In the idiopathic inflammatory myopathies, reactive oxygen species
      are at the crossroad between immune and non-immune cell mediated mechanisms' by
      Meyer et al.

PMID- 26293161
TI  - Incidence of skin and soft tissue infections in ambulatory and inpatient
      settings, 2005-2010.
AB  - BACKGROUND: The emergence of community-associated methicillin-resistant S. aureus
      was associated with dramatically increased skin and soft tissue infection (SSTI)
      incidence in the first few years of the 21(st) century in the U.S. However,
      subsequent trends are poorly understood. METHODS: We examined ambulatory and
      inpatient data of over 48 million persons years aged 0-64 years from the
      HealthCore Integrated Research Database (HIRD) between 2005 and 2010. Data were
      extracted from medical, pharmacy, and eligibility databases. We quantified SSTI
      incidence, type, and complications and comparative incidence trends for urinary
      tract infections (UTIs) and pneumonia. RESULTS: A total of 2,301,803 SSTIs were
      identified. Most SSTIs (95 %) were treated in the ambulatory setting and most (60
      %) were categorized as abscesses or cellulitis. During the study period, SSTI
      incidence remained relatively stable from 47.9 (95 % CI: 47.8-48.1) cases/1,000
      PY in 2005 to 48.5 cases/1,000 PY (95 % CI: 48.3-48.6) in 2010). Persons aged 45
      64 years had the highest incidence of both ambulatory-treated and inpatient
      treated SSTIs (51.2 (95 % CI: 51.1-51.3) and 3.87 (95 % CI: 3.84-3.90)
      cases/1,000 PY, respectively). SSTI complications such as myositis, gangrene, and
      sepsis occurred in 0.93 % (95 % CI: 0.92-0.94 %) and 16.92 % (95 % CI: 16.87
      16.97 %) of ambulatory-treated and inpatient-treated patients, respectively. SSTI
      incidence was approximately twice that of UTIs and tenfold of that of pneumonia.
      CONCLUSIONS: Among our large, diverse population of persons less than 65 years,
      SSTI incidence 2005 through 2010 has remained relatively constant at
      approximately 4.8 SSTIs per 100 person years, suggesting that previously observed
      increases in SSTI incidence remain sustained.

PMID- 26293163
TI  - Efficacy and safety of subcutaneous tabalumab, a monoclonal antibody to B-cell
      activating factor, in patients with systemic lupus erythematosus: results from
      ILLUMINATE-2, a 52-week, phase III, multicentre, randomised, double-blind,
      placebo-controlled study.
AB  - OBJECTIVES: To evaluate the efficacy and safety of tabalumab, a human IgG4
      monoclonal antibody that neutralises membrane and soluble B-cell activating
      factor (BAFF). METHODS: This randomised, placebo-controlled study enrolled 1124
      patients with moderate-to-severe systemic lupus erythematosus (SLE) (Safety of
      Estrogens in Lupus Erythematosus National Assessment- SLE Disease Activity Index
      >=6 at baseline). Patients received standard of care plus subcutaneous study
      drug, starting with a loading dose (240 mg) at week 0 and followed by 120 mg
      every 2 weeks (120 Q2W), 120 mg every 4 weeks (120 Q4W) or placebo. Primary
      endpoint was proportion achieving SLE Responder Index 5 (SRI-5) improvement at
      week 52. RESULTS: Clinical characteristics were balanced across groups. The
      primary endpoint was met with 120 Q2W (38.4% vs 27.7%, placebo; p=0.002), but not
      with the less frequent 120 Q4W regimen (34.8%, p=0.051). Although key secondary
      endpoints (time to severe flare, corticosteroid sparing and fatigue) were not
      met, patients treated with tabalumab had greater SRI-5 response rates in a
      serologically active subset and improvements in more stringent SRI cut-offs,
      SELENA-SLEDAI, Physician's Global Assessment, anti-double-stranded DNA
      antibodies, complement, total B cells and immunoglobulins. The incidences of
      deaths, serious adverse events (AEs), and treatment-emergent AEs were similar in
      the 120 Q2W, 120 Q4W and placebo groups, but depression and suicidal ideation,
      albeit rare events, were more commonly reported with tabalumab. CONCLUSION: SRI-5
      was met with 120 Q2W and although key secondary endpoints were not met, numerous
      other secondary endpoints significantly improved in addition to pharmacodynamic
      evidence of BAFF pathway blockade. The safety profile for tabalumab was similar
      to placebo, except for depression and suicidality, which were uncommon. TRIAL
      REGISTRATION NUMBER: NCT01205438.

PMID- 26293164
TI  - The circadian life of nocturnal water use: when late-night decisions help improve
      your day.

PMID- 26293165
TI  - Hearing loss in survivors of childhood head and neck rhabdomyosarcoma: a long
      term follow-up study.
AB  - OBJECTIVES: To determine the hearing status of survivors treated for head and
      neck rhabdomyosarcoma (HNRMS) at long-term follow-up. DESIGN: Cross-sectional
      long-term follow-up study. SETTING: Tertiary comprehensive cancer centre.
      PARTICIPANTS: Survivors treated for HNRMS during childhood in two concurrent
      cohorts; survivors in London had been treated with external beam radiotherapy
      (EBRT-based local therapy); survivors in Amsterdam were treated with AMORE
      (Ablative surgery, MOuld technique afterloading brachytherapy and surgical
      REconstruction) if feasible, otherwise EBRT (AMORE-based local therapy). MAIN
      OUTCOME MEASURES: We assessed hearing status of HNRMS survivors at long-term
      follow-up. Hearing thresholds were obtained by pure-tone audiometry. METHODS: We
      assessed the hearing thresholds, the number of patients with clinically relevant
      hearing loss and hearing impairment graded according to the Common Terminology
      Criteria for Adverse Events version 4.0 (CTCAEv4) and Boston criteria.
      Furthermore, we compared hearing loss between survivors treated with EBRT-based
      local therapy (London) and AMORE-based local therapy (Amsterdam). RESULTS:
      Seventy-three survivors were included (median follow-up 11 years). We found
      clinically relevant hearing loss at speech frequencies in 19% of survivors.
      Multivariable analysis showed that survivors treated with EBRT-based treatment
      and those with parameningeal tumours had significantly more hearing impairment,
      compared to survivors treated with AMORE-based treatment and non-parameningeal
      tumours. CONCLUSIONS: One in five survivors of HNRMS developed clinically
      relevant hearing loss. AMORE-based treatment resulted in less hearing loss
      compared to EBRT-based treatment. As hearing loss was highly prevalent and also
      occurred in survivors with orbital primaries, we recommend systematic
      audiological follow-up in all HNRMS survivors.

PMID- 26293166
TI  - Bacterial meningitis: an update of new treatment options.
AB  - The outcome of bacterial meningitis critically depends on the rapid initiation of
      bactericidal antibiotic therapy and adequate management of septic shock. In
      community-acquired meningitis, the choice of an optimum initial empirical
      antibiotic regimen depends on the regional resistance patterns. Pathogens
      resistant to antibacterials prevail in nosocomial bacterial meningitis.
      Dexamethasone is recommended as adjunctive therapy for community-acquired
      meningitis in developed countries. In comatose patients, aggressive measures to
      lower intracranial pressure <20 mmHg (in particular, external ventriculostomy,
      osmotherapy and temporary hyperventilation) were effective in a case-control
      study. Although many experimental approaches were protective in animal models,
      none of them has been proven effective in patients. Antibiotics, which are
      bactericidal but do not lyse bacteria, and inhibitors of matrix
      metalloproteinases or complement factor C5 appear the most promising therapeutic
      options. At present, vaccination is the most efficient method to reduce disease
      burden. Palmitoylethanolamide appears promising to enhance the resistance of the
      brain to infections. 

PMID- 26293167
TI  - Falsification Testing of Instrumental Variables Methods for Comparative
      Effectiveness Research.
AB  - OBJECTIVES: To demonstrate how falsification tests can be used to evaluate
      instrumental variables methods applicable to a wide variety of comparative
      effectiveness research questions. STUDY DESIGN: Brief conceptual review of
      instrumental variables and falsification testing principles and techniques
      accompanied by an empirical application. Sample STATA code related to the
      empirical application is provided in the Appendix. EMPIRICAL APPLICATION:
      Comparative long-term risks of sulfonylureas and thiazolidinediones for
      management of type 2 diabetes. Outcomes include mortality and hospitalization for
      an ambulatory care-sensitive condition. Prescribing pattern variations are used
      as instrumental variables. CONCLUSIONS: Falsification testing is an easily
      computed and powerful way to evaluate the validity of the key assumption
      underlying instrumental variables analysis. If falsification tests are used,
      instrumental variables techniques can help answer a multitude of important
      clinical questions.

PMID- 26293169
TI  - An Improved Equation for TBS and ADD: Establishing a Reliable Postmortem Interval
      Framework for Casework and Experimental Studies.
AB  - Megyesi et al.'s (J Forensic Sci, 2005, 50, 618) paper was important to forensic
      anthropology as it introduced a quantitative framework for estimating time since
      death in human cadavers, based upon physical appearance by way of scoring on a
      novel scale. However, errors concerning rounding, temperature scale, and
      incorrect use of a statistical regression model render their predictive formula
      unusable. Based upon only their more reliable data, a more appropriate regression
      model to predict accumulated degree days (ADD) from total body score (TBS) is
      presented. The new model is also a superior fit (r(2)  = 0.91) and produces
      markedly narrower confidence intervals than the original, which also allowed
      impossible, negative ADD values. Explanations of the shortcomings in the original
      analysis and calculations are presented, which it is hoped will help forensic
      scientists avoid making similar mistakes. 

PMID- 26293170
TI  - A double-blinded, randomized, vehicle-controlled study to access skin
      tolerability and efficacy of an anti-inflammatory moisturizer in treatment of
      acne with 0.1% adapalene gel.
AB  - INTRODUCTION: Topical retinoids are considered to be the first-line agents and
      maintenance therapy of acne; however, irritation side effects are major concern
      issues. Noncomedogenic moisturizers are sometimes added to relieve cutaneous
      irritations. This study aimed to compare tolerability and efficacy of
      moisturizers containing licochalcone A, l-carnitine and 1,2-decanediol (active
      formulation) with a placebo in mild to moderate severe acne in Asian subjects.
      METHODS: This was an 8-week double-blind, prospective, randomized controlled
      study. All patients (n = 120) were randomized equally into three groups: (A)
      adapalene gel, (B) adapalene gel with the active formulation and (C) adapalene
      gel with the placebo. The severity of acne, skin bioengineering measurements and
      skin tolerability were recorded during the study. RESULTS: Compared to baseline,
      the active formulation group showed significant reductions in inflammatory
      lesions and total lesions at the end of the study without flare-up. Moreover,
      skin irritations were less detected than in the other two groups by corneometer
      and transepidermal water loss measurements. CONCLUSIONS: The concomitant usage of
      adapalene gel and the moisturizer containing licochalcone A, l-carnitine and 1,2
      decanediol could reduce undesirable side effects without interfering the efficacy
      of adapalene. This moisturizer may be superior to placebo to prevent cutaneous
      irritations and enhance patients' adherence to acne medications.

PMID- 26293171
TI  - European Heart Rhythm Association/Heart Failure Association joint consensus
      document on arrhythmias in heart failure, endorsed by the Heart Rhythm Society
      and the Asia Pacific Heart Rhythm Society.

PMID- 26293172
TI  - Dual inducer signal recognition by an Mlc homologue.
AB  - The Mlc transcription factor in Escherichia coli controls the expression of the
      phosphotransferase system genes implicated in the transport of glucose into the
      cell. Transport of glucose derepresses Mlc-repressed genes by provoking the
      sequestration of Mlc to the membrane, via an interaction with the
      dephosphorylated EIIB domain of the glucose transporter, PtsG. NagC, a paralogue
      of Mlc in E. coli, regulates the use of the amino sugar N-acetylglucosamine
      (GlcNAc). Both Mlc and NagC are members of the ROK (Repressors, ORFs and Kinases)
      family. Vibrio cholerae expresses a close orthologue of Mlc, VC2007, which
      represses the Mlc target, ptsG, in E. coli. However, VC2007 is not sensitive to
      growth on glucose but responds to growth on N-acetylglucosamine (GlcNAc). We show
      that growth on GlcNAc generates two different signals, which relieve VC2007
      repression of ptsG in E. coli. The majority of the loss of repression is due to
      VC2007 interacting with dephosphorylated NagE, the GlcNAc-specific transporter.
      However, a minor part is due to VC2007 binding GlcNAc6P. These two inducing
      signals are independent and can be separated by mutations in VC2007 eliminating
      sensitivity to one or other signal. In addition we show that, although most
      induction of Mlc-repressed genes is dependent upon the interaction of Mlc with
      PtsG in E. coli, Mlc can also bind to NagE, but it is not sensitive to GlcNAc6P.
      These observations shed light on how ROK family homologues have evolved in their
      ability to sense glucose and GlcNAc and of the shift between recognition of
      different categories of inducer. 

PMID- 26293173
TI  - Leveraging nanotechnology for enrichment of circulating tumor cells in vivo.

PMID- 26293174
TI  - Does Articaine Provide an Advantage over Lidocaine in Patients with Symptomatic
      Irreversible Pulpitis? A Systematic Review and Meta-analysis.
AB  - INTRODUCTION: Achieving profound pulpal anesthesia can be difficult in patients
      with symptomatic irreversible pulpitis. This study provides a systematic review
      and meta-analysis to address the population, intervention, comparison, outcome
      (PICO) question: in adults with symptomatic irreversible pulpitis who are
      undergoing endodontic treatment, what is the comparative efficacy of articaine
      compared with lidocaine in reducing pain and incidence of adverse events?
      METHODS: A protocol was prepared and registered on PROSPERO. Electronic searches
      were conducted in MEDLINE, Scopus, Cochrane Library, and ClinicalTrials.gov by
      using strict inclusion and exclusion criteria. Two independent reviewers assessed
      eligibility for inclusion and quality. Weighted anesthesia success rates and 95%
      confidence intervals (CIs) were estimated and compared by using a random-effects
      model. RESULTS: Two hundred seventy-five studies were initially identified from
      the search; 10 double-blind, randomized clinical trials met the inclusion
      criteria. For combined studies, articaine was more likely than lidocaine to
      achieve successful anesthesia (odds ratio [OR], 2.21; 95% CI, 1.41-3.47; P =
      .0006; I(2) = 40%). Maxillary infiltration subgroup analysis showed no
      significant difference between articaine and lidocaine (OR, 3.99; 95% CI, 0.50
      31.62; P = .19; I(2) = 59%). For combined mandibular anesthesia studies articaine
      was superior to lidocaine (OR, 2.20; 95% CI, 1.40-3.44; P = .0006; I(2) = 30%),
      with further subgroup analysis showing no difference for mandibular block
      anesthesia (OR, 1.44; 95% CI, 0.87-2.38; P = .16; I(2) = 0%). When used for
      supplemental infiltration after successful mandibular block anesthesia, articaine
      was significantly more effective than lidocaine (OR, 3.55; 95% CI, 1.97-6.39; P <
      .0001; I(2) = 9%). There were no reports of adverse events. CONCLUSIONS: This
      systematic review of double-blind, randomized clinical trials provides level 1
      evidence to support the use of articaine for patients with symptomatic
      irreversible pulpitis. There is a significant advantage to using articaine over
      lidocaine for supplementary infiltration after mandibular block anesthesia but no
      advantage when used for mandibular block anesthesia alone or for maxillary
      infiltration.

PMID- 26293175
TI  - Erratum to: Extraneural metastases in glioblastoma patients: two cases with YKL
      40-positive glioblastomas and a meta-analysis of the literature.

PMID- 26293176
TI  - Gas holdup in cyclone-static micro-bubble flotation column.
AB  - The present work has been carried out to investigate the effect of process
      variables on gas holdup and develop an empirical equation and a neural network
      model for online process control of the gas holdup based on the operating
      variables. In this study, the effect of process variables (nozzle diameter,
      circulation pressure, aeration rate, and frother dosage) on gas holdup in a
      cyclone-static micro-bubble flotation column of an air/oily wastewater system was
      investigated. Gas holdup was estimated using a pressure difference method and an
      empirical equation was proposed to predict gas holdup. A general regression
      neural network (GRNN) model was also introduced to predict gas holdup for the
      cyclone-static micro-bubble flotation column. The predictions from the empirical
      equation and the GRNN are in good agreement with the experiment data for gas
      holdup, while the GRNN provides higher accuracy and stability compared with that
      of the empirical equation. 

PMID- 26293177
TI  - Cognition in individuals at risk for Parkinson's: Parkinson associated risk
      syndrome (PARS) study findings.
AB  - OBJECTIVES: The Parkinson Associated Risk Syndrome Study identified a cohort of
      healthy adults with hyposmia and dopamine transporter binding reduction to
      characterize individuals at risk for Parkinson's disease (PD). We describe the
      cognitive profile of this cohort. METHODS: Individuals older than 50 y without PD
      were recruited. Two hundred twenty-five completed cognitive testing and were
      included in the final analysis. A neuropsychological test battery was
      administered and normative scores created for global cognition, memory, executive
      function/working memory, processing speed/attention, visuospatial abilities, and
      language domains. Other non-motor symptoms (constipation, depression, anxiety,
      and rapid eye movement sleep behavior disorder) were assessed through
      questionnaires. RESULTS: Individuals with both hyposmia and reduced dopamine
      transporter binding (n = 38) had lower mean scores for global cognition,
      executive function/working memory, and memory compared with all other
      participants (n = 187). In separate multivariate logistic regression models,
      lower global cognition (odds ratio, 1.97, P = 0.004), and specifically executive
      function/working memory (odds ratio, 1.84, P = 0.004) scores were associated with
      membership in the hyposmia with dopamine transporter reduction group. Combining
      hyposmia with relative impairment on specific cognitive domains increased the
      odds of dopamine transporter binding reduction compared with hyposmia alone, with
      the greatest increase in odds for hyposmia plus executive function/working memory
      relative impairment (68% increase in odds from 4.14 to 6.96). CONCLUSION: Changes
      in global cognitive abilities, and specifically executive function/working
      memory, are present in individuals at risk for PD. Combining non-motor features,
      including cognition, improves prediction of dopamine transporter binding
      reduction.

PMID- 26293179
TI  - Males matter: Increased home range size is associated with the number of resident
      males after controlling for ecological factors in wild Assamese macaques.
AB  - OBJECTIVES: There is increasing evidence of male resource defense during
      intergroup encounters in non-human primates. Only few studies showed a
      reproductive benefit of having more males in a group, and evidence only comes
      from territorial species, or from species with relatively small male group sizes
      where males are less prone to suffer from collective action problems. We
      investigated the effect of male group size on home range size and female
      reproductive success in a non-territorial species with male dispersal and large
      male group sizes. METHODS: We studied one wild group of Assamese macaques (Macaca
      assamensis) by following them almost daily (June 2006-September 2012) and
      collected spatial, behavioral, climate and spatiotemporal data on food plants.
      RESULTS: Among ecological factors, decreasing rainfall and a statistical
      interaction between food abundance and distribution were positively related to
      home range size. After controlling for ecological predictors, we found that male
      group size but not overall group size had a significant positive effect on full
      and core home range size. A simple correlation analysis suggests that such an
      increase in home range area, presumably increasing access to food resources, can
      be associated with increased female fecundity measured as the proportion or the
      number of females conceiving in a given year. DISCUSSION: Within the limitations
      of this study, the results suggest that male resource defense could be a strategy
      benefitting both sexes if male reproductive skew was low and many males benefited
      from increased female fertility.

PMID- 26293178
TI  - Inhibition of Lactate Transport Erases Drug Memory and Prevents Drug Relapse.
AB  - BACKGROUND: Drug memories that associate drug-paired stimuli with the effects of
      abused drugs contribute to relapse. Exposure to drug-associated contexts causes
      consolidated drug memories to be in a labile state, during which manipulations
      can be given to impair drug memories. Although substantial evidence demonstrates
      the crucial role of neuronal signaling in addiction, little is known about the
      contribution of astrocyte-neuron communication. METHODS: Rats were trained for
      cocaine-induced conditioned place preference (CPP) or self-administration and
      microinjected with the glycogen phosphorylation inhibitor 1,4-dideoxy-1,4-imino-D
      arabinitol into the basolateral amygdala (BLA) immediately after retrieval. The
      concentration of lactate was measured immediately after retrieval via
      microdialysis, and the CPP score and number of nosepokes were recorded 24 hours
      later. Furthermore, we used antisense oligodeoxynucleotides to disrupt the
      expression of astrocytic lactate transporters (monocarboxylate transporters 1 and
      2) in the BLA after retrieval, tested the expression of CPP 1 day later, and
      injected L-lactate into the BLA 15 minutes before retrieval to rescue the effects
      of the oligodeoxynucleotides. RESULTS: Injection of 1,4-dideoxy-1,4-imino-D
      arabinitol into the BLA immediately after retrieval prevented the subsequent
      expression of cocaine-induced CPP, decreased the concentration of lactate in the
      BLA, and reduced the number of nosepokes for cocaine self-administration.
      Disrupting the expression of monocarboxylate transporters 1 and 2 in the BLA also
      caused subsequent deficits in the expression of cocaine-induced CPP, which was
      rescued by pretreatment with L-lactate. CONCLUSIONS: Our results suggest that
      astrocyte-neuron lactate transport in the BLA is critical for the reconsolidation
      of cocaine memory.

PMID- 26293180
TI  - Minimally resective epilepsy surgery in MRI-negative children.
AB  - AIM: Performing epilepsy surgery on children with non-lesional brain MRI often
      results in large lobar or multilobar resections. The aim of this study was to
      determine if smaller resections result in a comparable rate of seizure freedom.
      METHODS: We reviewed 25 children who had undergone focal corticectomies
      restricted to one aspect of a single lobe or the insula at our institution within
      a 5.5-year period. Data collected in the comprehensive non-invasive pre-surgical
      evaluation (including scalp video-EEG, volumetric MRI, functional MRI, EEG source
      localization, and SPECT and PET), as well as from invasive recordings performed
      in each patient, was reviewed. Data from each functional modality was identified
      as convergent or divergent with the epileptogenic zone using image
      coregistration. Specific biomarkers (from extra-operative and invasive testing)
      previously indicated to be indicative of focal epileptogenicity were used to
      further tailor each resection to an epileptogenic epicentre. Tissue pathology and
      postoperative outcomes were obtained from all 25 patients. RESULTS: Two years
      postoperatively, 15/25 (60%) children were seizure-free, three (12%) experienced
      >90% reduction in seizure frequency, two (8%) had a 50-90% reduction in seizure
      frequency, and the remaining five (20%) had no change in seizure burden. There
      was no significant difference in outcome based on numerous pre- and postoperative
      factors including location of resection, the number of preoperative functional
      tests providing convergent data, and tissue pathology. CONCLUSION: In MRI
      negative children with focal epilepsy, an epileptogenic epicentre within a larger
      epileptogenic zone can be identified when specific biomarkers are recognized on
      non-invasive and invasive testing. When such children undergo resection of a
      small, well-defined epileptogenic epicentre, favourable outcomes can be achieved.

PMID- 26293182
TI  - How Should the Prevalence of Urinary Incontinence Be Determined in a Female
      Population?

PMID- 26293181
TI  - Unexpected Long-term Improvements in Urinary and Erectile Function in a Large
      Cohort of Men with Self-reported Outcomes Following Radical Prostatectomy.
AB  - BACKGROUND: It is generally assumed that if a man does not regain urinary
      continence or erectile function within 12 mo of radical prostatectomy (RP), then
      the chance of subsequent recovery is low. OBJECTIVE: To determine the probability
      of achieving good urinary function (UF) or erectile function (EF) up to 48 mo
      postoperatively in men who reported poor UF or EF at 12 mo after RP. DESIGN,
      SETTING, AND PARTICIPANTS: We identified 3187 patients who underwent RP from 2007
      through 2013 at a tertiary institution and had extended multidisciplinary follow
      up with patient-reported UF and EF scores at >=12 mo. INTERVENTION: Open or
      minimally invasive RP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary
      outcome was good UF as defined by a urinary score >=17 (range: 0-21) or good EF
      as defined by a modified International Index of Erectile Function-6 score >=22
      (range: 1-30). The probability of functional recovery beyond 12 mo was determined
      by Kaplan-Meier analyses. RESULTS AND LIMITATIONS: Among patients incontinent at
      12 mo, the probability of achieving good UF at 24, 36, and 48 mo was 30%, 49%,
      and 59%. In patients experiencing erectile dysfunction at 12 mo, the probability
      of recovering EF at 24, 36, and 48 mo was 22%, 32%, and 40%. On multivariable
      analyses, 12-mo functional score and age were associated with recovery, but only
      score was consistently significant. CONCLUSIONS: Men with incontinence or
      erectile dysfunction at 12 mo have higher than anticipated rates of subsequent
      functional improvement. Probability of recovery is strongly influenced by score
      at 12 mo. Further research should address the impact of ongoing multidisciplinary
      follow-up care on our observed rates of recovery. PATIENT SUMMARY: Many prostate
      cancer patients continue to recover urinary and erectile function after 12 mo.
      The level of functional recovery by 12 mo is associated with long-term recovery
      and should be discussed by the physician and patient when deciding on
      rehabilitative interventions.

PMID- 26293183
TI  - Natural estrogens in dairy products: Determination of free and conjugated forms
      by ultra high performance liquid chromatography with tandem mass spectrometry.
AB  - Natural estrogens are synthesized by mammals in different amounts depending on
      the developmental stage and pregnancy/lactation period, and they may pass into
      milk, where they are mostly present as glucuronated and sulfated forms. In modern
      dairy practices, about 75% of milk is produced from pregnant cows; therefore, the
      amount of hormones that may pass into milk could be of concern. While estrogen
      determination in milk has been investigated in depth, the individual
      determination of estrogens and their conjugated forms in dairy products has not
      been fully addressed. The aim of this work was to develop and assess a sensitive
      method, using the peculiar retention properties of graphitized carbon black, to
      extract natural free estrogens and their major conjugated metabolites, without
      any enzymatic cleavage, from yogurt, cheese, and butter. The free and conjugated
      estrogens were eluted in two distinct fractions from the solid-phase extraction
      cartridge and analyzed separately by ultra high performance liquid chromatography
      coupled to tandem mass spectrometry. Recoveries were higher than 80% for all the
      three sample typologies. The highest matrix effects were observed for butter,
      which was richest in lipid content, but was below 30%. A survey on some
      commercial dairy products suggests that production processes decreased estrogen
      content. 

PMID- 26293184
TI  - Functional characterization of two new STAT3 mutations associated with hyper-IgE
      syndrome in a Mexican cohort.
AB  - Hyper-IgE syndrome (HIES) is an immunodeficiency disorder that is characterized
      by distinctive immunologic and non-immunologic manifestations. Although mutations
      in signal transducer and activator of transcription 3 (STAT3) have been
      associated with HIES, the exact nature of the relationship is unknown. Here, we
      characterized the functional activity of STAT3 and its mutations in 11 Mexican
      patients with autosomal dominant HIES. STAT3 phosphorylation was evaluated by
      flow cytometry, and in silico analyses were performed to estimate the impact of
      allelic mutations on the DNA binding and SH2 domains of the STAT3 protein.
      Electrophoretic mobility shift assays were used to assess whether the STAT3
      mutants could bind to the consensus oligonucleotide target in vitro. Two novel
      mutations [g.58891A>T (Asn395Tyr) and g.59078A>T (Asn425Tyr)] as well as one
      possible somatic mosaicism were found in several of the patients who bore some
      remarkable features. However, there were no direct correlations between genotypes
      and HIES clinical features. STAT3 phosphorylation was found to be lower in the
      patient cohort than in healthy controls. Moreover, the mutated STAT3 proteins
      could bind to the Sp1, but not to the STAT3, consensus sequence. From these
      functional studies, the STAT3 mutations found in our patient cohort were
      concluded to be deleterious for normal STAT3 function. 

PMID- 26293185
TI  - Elevation of the maxillary sinus membrane for de-novo bone formation: First
      results of a prospective study in humans.
AB  - PURPOSE: Sinus floor elevation via the lateral window approach represents a
      reliable technique for bone augmentation in the atrophic posterior maxilla. It is
      known that sinus membrane elevation leads to new bone formation. This prospective
      clinical study compared a specific technique in sinus membrane elevation with a
      conventional sinus floor augmentation (xenogenous/autogenous bone) in a human
      split mouth model. METHODS: Five edentulous patients with highly atrophic
      posterior maxillae were included in this study. On one maxillary side a
      degradable PDLLA-membrane was placed to create a space underneath the sinus
      membrane. Contralateral a mixture of autogenous and xenogenous bone was used for
      sinus floor augmentation. A two-stage procedure was carried out. The following
      variables were assessed: bone regeneration on cone-beam computed tomography (cone
      beam CT), implant success, prosthetic comfort and patient satisfaction. Bone
      biopsies were taken with simultaneous implant placement. The samples were
      histologically analyzed. RESULTS: Cone-beam CTs revealed new bone formation on
      both sides. Thirty implants were placed, 15 in the augmented region and 15 in the
      non-augmented side. Thirty bone biopsies were taken and evaluated. Vital new bone
      was detected on the experimental side (osteoinductivity). On the conventional
      side a mixture of autogenous and residual bone substitute material was seen
      (osteoconductivity). Implant survival was 100% so far. Patient's satisfaction was
      high and prosthetic complications were not encountered. CONCLUSION: As it
      provides the highest rate of bone formation, autogenous bone in combination with
      bone substitute material can be considered as a very reliable standard procedure
      in sinus floor augmentation. The specific sinus membrane elevation technique as
      presented here showed satisfying results and might be a suitable alternative for
      maxillary sinus augmentation.

PMID- 26293186
TI  - Aberrant facial flushing following monobloc fronto-facial distraction.
AB  - BACKGROUND: Patients with syndromic forms of craniosynostosis may experience
      functional problems such as raised intracranial pressure, proptosis, obstructive
      sleep apnoea and failure to thrive. The monobloc fronto-facial advancement with
      osteogenic distraction is increasingly used to correct these functional problems
      in one procedure as well as improve appearance. The authors report the phenomenon
      of post operative aberrant facial flushing - an unusual and previously unreported
      complication of the procedure. METHODS: The case notes of 80 consecutive patients
      undergoing fronto-facial advancement by distraction using the rigid external
      distraction device (RED) were reviewed for features of aberrant facial flushing.
      RESULTS: Four out of eighty individuals developed facial flushing after monobloc
      fronto-facial distraction using the rigid external distractor (RED) frame. All
      were female with Crouzon or Pfeiffer syndromes causing the severe functional
      problems for which they underwent the surgery. They were aged 6-8 years.
      Following removal of the frame, they developed intermittent but severe facial
      flushing. The flushing spontaneously settled in three patients after up to four
      years but persists in the other child seven years after her surgery. CONCLUSION:
      Aberrant facial flushing is a rare but significant complication of monobloc
      fronto-facial surgery. It occurred in 4 of our 80 (5%) patients. The skull base
      osteotomies essential for the procedure are made anterior to the pterygopalatine
      ganglion and it is our contention that damage from these was responsible for a
      neuropraxia of its efferent nerve branches. A review of the autonomic control of
      the facial vascular system suggests that the phenomenon is due to an unequal
      process of recovery that leaves the cutaneous vasodilating parasympathetic or
      beta-adrenergic innervation relatively unopposed - a situation that persists
      until with time a normal balance of autonomic input is achieved.

PMID- 26293187
TI  - A three-dimensional comparison of the pharyngeal airway after mandibular
      distraction osteogenesis and bilateral sagittal split osteotomy.
AB  - PURPOSE: The goal of this retrospective study was to examine the radiological
      changes in the pharyngeal airway following mandibular distraction osteogenesis
      (DO) and bilateral sagittal split osteotomy (BSSO). MATERIAL AND METHODS: Between
      2005 and 2009, a total of 41 nonsyndromic patients underwent a mandibular
      osteotomy (nDO = 23; nBSSO = 18). Digital volume tomography images were created
      for preoperative and postoperative evaluations of both groups. The Dolphin 3D
      program was used for comparative analysis of the pharyngeal airways. RESULTS:
      After DO, the airway volumes (VOL) improved by 6.8 mL. In comparison, an
      improvement of 5.9 mL was observed as result of BSSO. The minimum axial areas
      (AREA) of the enlargements increased by 109.1 mm(2) with DO and 103.1 mm(2) with
      BSSO. The airway areas (SA) increased by 193.8 mm(2) with DO and 185.2 mm(2) with
      BSSO. There were no significant differences between two surgical procedures in
      terms of the parameters describe above (pVOL = 0.358; pAREA = 0.752; pSA =
      0.777). However, the initial preoperative values (pVOL = 0.020; pAREA = 0.005)
      and the patients' ages (pAREA = 0.042; pSA = 0.007) did have significant effects
      on the postoperative values. CONCLUSION: Both DO and BSSO expanded the pharyngeal
      airways of all nonsyndromic patients.

PMID- 26293188
TI  - Selective neck dissection for neck residue of nasopharyngeal carcinoma: A
      prospective study.
AB  - PURPOSE: Cervical residue or recurrence of nasopharyngeal carcinoma (NPC) is
      traditionally treated with radical neck dissection (RND). Because cervical
      residue patients with NPC exhibit better prognoses than patients with neck
      recurrence, selective neck dissection (SND) rather than RND may be the optimal
      treatment for these patients. This study was designed to evaluate the efficacy of
      SND for the management of neck residue of NPC. MATERIAL AND METHODS: Between
      January 2008 and July 2013, a total of 69 patients were assigned to undergo
      either RND or SND in the Department of Head and Neck Surgery at Fudan University
      Cancer Center. The patients' clinical and pathological characteristics,
      complications, and treatment outcomes were evaluated and analyzed. RESULTS: Our
      study consisted of 69 patients, including 51 in the RND group and 18 in the SND
      group. There was no significant difference in any clinical or pathological
      characteristic between the two groups. The overall survival (OS), disease-free
      survival (DFS), and regional-free survival of all the patients were 79.70%,
      61.43%, and 83.30%, respectively, at 3 years and 66.81%, 47.43%, and 78.67%,
      respectively, at 5 years. No statistically significant difference was found in
      the OS, DFS, or regional-free survival between the RND and SND groups. The total
      complication rate was much lower in the SND group (11.11%) than in the RND group.
      The patients in the RND group experienced longer hospitalization and
      postoperative hospitalization than those in the SND group. CONCLUSION: SND was
      demonstrated to be safe and effective for the treatment of neck residue of NPC.
      The results indicated that patients with neck residue disease who are at stage II
      to III with a single enlarged lymph node (<1 cm) and only one positive
      pathological lymph node may benefit the most from SND.

PMID- 26293189
TI  - Endoscopic-assisted gland preserving therapy for the management of parotid gland
      sialolithiasis: Our preliminary experience.
AB  - OBJECTIVE: To analyze the efficacy and safety of sialendoscopy and a combined
      transoral or transcutaneous and sialendoscopic approach in the removal of parotid
      gland sialoliths. METHODS: This retrospective study included 29 patients
      diagnosed with parotid gland sialolithiasis who required endoscopic-assisted
      gland preserving therapy. Ultrasonography and computed tomography were used to
      diagnose parotid sialolithiasis. The use of interventional sialendoscopy,
      sialendoscopic-transoral, or sialendoscopic-transcutaneous procedures was
      determined by the characteristics of the parotid gland stones. RESULTS: The
      stones were extracted by interventional sialendoscopy in nine patients. The
      transoral procedure was performed in 15 patients with large stones which were
      impacted in the ductal wall. The remaining five patients were managed through an
      external approach via a local incision under sialendoscopy. No postoperative
      complications occurred. The parotid glands were functioning normally after the
      procedures. CONCLUSION: The combined sialendoscopic-transoral and sialendoscopic
      transcutaneous operation appears to be a good alternative for parotid gland
      sialolithiasis in the absence of lithotripsy devices. This type of therapy can,
      therefore, decrease the rate of parotidectomy.

PMID- 26293190
TI  - Modified facelift approach combined with a superficial musculoaponeurotic system
      flap in the treatment of benign parotid tumors.
AB  - PURPOSE: The purpose of this study was to investigate the adequacy of a modified
      facelift incision combined with an SMAS flap for the resection of benign parotid
      lesions in terms of cosmesis and incidence of Frey's syndrome. MATERIALS AND
      METHODS: A hundred patients who underwent superficial parotidectomy were divided
      into 2 groups according to approach: Blair incision (57 cases) and modified
      facelift incision (43 cases). In the latter group, 36 patients were reconstructed
      with a superficial musculoaponeurotic system (SMAS) flap. During follow-up,
      patients were asked to rate their satisfaction with their postoperative
      appearance using a 1 to 3 scale. RESULTS: Clinical Frey's syndrome was present in
      8.5% of patients with SMAS flap, and in 19% patients without SMAS flap (p =
      0.16). The average cosmetic outcome score for patients who underwent a modified
      facelift approach combined with an SMAS flap was 2.87, whereas patients whose
      tumors were approached through a Blair incision reported a lower score of 2.1 (p
      < 0.005). CONCLUSION: A modified facelift incision combined with an SMAS flap
      improved the cosmetic appearance of patients who underwent extrafacial or
      superficial parotidectomy. In addition, this flap seems to reduce the occurrence
      of Frey's syndrome.

PMID- 26293191
TI  - A 3D morphometric follow-up analysis after frontoorbital advancement in non
      syndromic craniosynostosis.
AB  - OBJECTIVE: Frontoorbital advancement (FOA) in patients with non-syndromic
      craniosynostosis mainly addresses the aesthetic and functional correction of the
      frontoorbital region. To help define the operative strategy and any follow-up
      assessments after surgical correction, objective parameters describing the
      critical regions of skull deformity are essential. Based on 3D morphometric
      analysis, new parameters for the documentation of changes of the frontoorbital
      bandeau were developed in a prospective study. METHODS AND MATERIALS: In a
      prospective series, 13 children with non-syndromic craniosynostosis (seven
      metopic, four unilateral coronal, and two bilateral coronal) treated with
      frontoorbital advancement, underwent detailed morphometric and volumetric
      evaluation using a 3D light optical scan system (3D-Shape, Erlangen, Germany).
      Measurements were obtained preoperatively and at 3, 6 and 12 months
      postoperatively with newly developed parameters generated by cephalometric
      analysis software (Onyx Ceph, Image Instruments, Chemnitz, Germany). RESULTS: In
      most patients, frontoorbital advancement resulted in stable long-term results
      without growth inhibition and with normalization or improvement of ongoing skull
      development. The mean frontal angle was 145 degrees  and the frontoparietal angle
      137-140 degrees . The cephalic index was normalized or markedly improved. Head
      circumference and head height increased significantly (p = 0.001 and p = 0.002,
      respectively). These changes were confirmed in all postoperative measurements.
      CONCLUSION: During the 12-month follow-up period all angle parameters proved to
      be stable and no major impairment of normal skull growth was observed after FOA.
      The frontoorbital angle is a useful parameter in evaluating long-term outcome.
      The frontoparietal angle is important for the stability of the frontoparietal
      region, in which a certain growth inhibition may be observed postoperatively.

PMID- 26293192
TI  - Impact of Actinomyces naeslundii on bisphosphonate-related osteonecrosis of the
      jaws in ovariectomized rats with periodontitis.
AB  - Bisphosphonates-related osteonecrosis of the jaws (BRONJ) is a severe
      complication of BPs therapy with unknown pathogenesis. This study aimed to
      evaluate the impact of Actinomyces naeslundii (A. naeslundii) on the progression
      of BRONJ in ovariectomized (OVX) rat model with periodontal diseases. Sixty rats
      were randomly assigned into four groups. All rats underwent bilateral
      ovariectomy. Six weeks after surgery, animals with periodontitis induced by
      ligature placement were administrated with normal saline (NS), NS &A. naeslundii
      inoculation, zolecdronic acid (ZA) and ZA &A. naeslundii inoculation for 12
      weeks, respectively. Loads of total bacteria and A. naeslundii in the mouth were
      assessed by real time PCR. After sacrifice, the mandibles were harvested for
      micro-computed tomography (micro-CT) and histological examination. Real-time PCR
      demonstrated that A. naeslundii was not routinely found in the rats and ZA
      treatment did not promote its accumulation. Micro-CT examination disclosed that
      ligature placement induced significant alveolar bone loss, which was greatly
      attenuated by ZA treatment and aggravated by A. naeslundii. Histological
      assessment demonstrated that ZA treatment increased the risk of developing BRONJ
      like disease but this condition was not worsen with the presence of A.
      naeslundii. Our study suggested that oral A. naeslundii inoculation aggravated
      periodontal disease but not BRONJ in our animal model. 

PMID- 26293193
TI  - Long-term skeletal and dental stability after orthognathic surgery of the maxillo
      mandibular complex in Class II patients with transverse discrepancies.
AB  - INTRODUCTION: Two-jaw surgery has become the standard procedure for correcting
      skeletal maxillo-mandibular discrepancies in adults. However, only a few studies
      have reported on the long-term stability of bimaxillary orthognathic surgery in
      patients with Class II malocclusion and transverse discrepancies. In this study,
      the long-term outcome of two-piece maxillary treatment during bimaxillary surgery
      in patients with skeletal Class II malocclusion was examined and the results are
      discussed. MATERIAL AND METHODS: Dental plaster casts and lateral cephalograms of
      47 patients were collected in five phases of treatment: baseline (t1),
      preoperatively (t2), postoperatively (t3), at the end of orthodontic treatment
      (t4), and at the time of long-term follow-up (t5), and were retrospectively
      analyzed. RESULTS: At follow-up all patients showed a Class I occlusion. The
      maxillary width was, on average, enlarged by 2.7 mm surgically. During the
      following 8.8 years after treatment, 1.7 mm were lost. The cephalometric analyses
      showed no severe changes in the sagittal maxillary position for the duration of
      follow-up. The sagittal mandibular position (SNB) was changed significantly by
      the mandibular advancement from 75.4 degrees  to 77.8 degrees  and remained
      stable for 8.8 years postoperatively. CONCLUSION: Bimaxillary surgery with two
      piece maxillary treatment in patients with Class II malocclusion leads to stable
      long-term occlusal results in the sagittal plane. The transverse enlargement
      achieved by intraoperative widening does not remain stable over the years. A
      relapse of about 60% of the surgically expanded transverse width is seen. In
      Class II deformities without an open bite, where extended transverse enlargement
      is necessary, a two-step procedure with primary surgically-assisted rapid palatal
      expansion followed by one-piece surgery should be planned.

PMID- 26293194
TI  - [Gene therapy as a treatment concept for inherited retinal diseases].
AB  - BACKGROUND: Gene therapy for inherited retinal diseases (IRDs) is currently being
      validated in several clinical trials and is becoming a promising therapeutic
      option for these previously incurable diseases. OBJECTIVES: The aim of this
      review is to give an overview of the concept, the application and the challenges
      associated with gene therapy. In particular, the pertinence of gene therapy for
      IRDs will be highlighted along with ongoing clinical trials in the field.
      MATERIAL AND METHODS: A systematic review of relevant entries on gene therapy and
      on gene therapy for IRDs, in particular in PubMed and ClinicalTrials.gov.
      RESULTS: Gene therapy is emerging not only as a therapy for monogenetic retinal
      diseases but also for complex genetic diseases, such as neovascular age-related
      macular degeneration. The discovery of adeno-associated viral vectors (AAVs) has
      marked a great improvement for IRD gene therapy. All clinical studies since 2006
      demonstrated the safety and initial efficacy; however, not all expectations based
      on very successful preclinical studies were met. CONCLUSION: In future we can
      expect gene therapy to continue to become more clinically relevant. More than
      ever, it is now essential to generate precise characterizations of the natural
      disease progression of IRDs through observational or retrospective studies in
      order to guarantee a most effective study design.

PMID- 26293195
TI  - [Surgical treatment with an artificial iris].
AB  - Iris defects with their disturbed pupillary function, visual impairment and glare
      constitute a therapeutic challenge in surgical reconstruction. A new therapeutic
      option for distinctive defects consists in the implantation of a custom-made
      silicone iris. This new and challenging therapy provides the opportunity to
      achieve an individual, aesthetically appealing and good functional result for the
      patient. 

PMID- 26293196
TI  - The Effect of Preintervention Preparation on Pain and Anxiety Related to
      Peripheral Cannulation Procedures in Children.
AB  - This study was performed to determine the effect of several preintervention
      preparation practices on pain and anxiety related to the peripheral cannulation
      procedure in children ages 9-12 years. The study included 60 Turkish children (28
      female, 32 male, randomly selected by lot), 30 of whom were included in the
      intervention group and 30 of whom were included in the control group. The
      children's demographic data were collected by a data collection form prepared by
      the researcher. The children in the intervention group read the training manual
      before peripheral cannulation, and the procedure was demonstrated on a teddy
      bear. Their level of pain was assessed using the Wong-Baker Faces Rating Scale,
      and their level of anxiety was determined by the Spielberger State-Trait Anxiety
      Inventory for Children, before and during the procedure in both groups. Results
      showed that while anxiety and pain scores increased during the actual procedure
      compared to the preparatory procedure in the control group (anxiety t = -4.957,
      pain Z(a) = -4.048), anxiety and pain scores decreased during the actual
      procedure in the intervention group compared to the preparatory procedure
      (anxiety t = 7.896, pain t = 6.196). When the pain and anxiety scores were
      examined, it was found that both anxiety and pain scores in the intervention
      group were significantly lower than in the control group. In conclusion, children
      in this study experienced pain and situational anxiety during peripheral
      cannulation, and this pain can be reduced by preparing the child in advance of
      the procedure. It is suggested that children should be informed about and able to
      practice the procedure on a toy or model before peripheral cannulation.
      Preparation of the children to painful procedures in accordance with their
      cognitive development can reduce anxiety and pain. 

PMID- 26293197
TI  - In Lumbar Fusion Patients, How Does Establishing a Comfort Function Goal
      Preoperatively Impact Postoperative Pain Scores?
AB  - The purpose of this feasibility study was to determine the impact of establishing
      a comfort function goal preoperatively on postoperative pain scores and opiate
      requirements in lumbar fusion patients. A comfort function goal is defined as the
      pain score identified by the patient describing the level of pain tolerance to
      participate in healing activities such as deep breathing, ambulation and
      participation in activities of daily living. The design was prospective,
      nonrandomized, intervention group (n = 30) compared with retrospective chart
      review as control group (n = 30). Sample included patients scheduled for routine
      lumbar fusion in an urban southeastern hospital. The study intervention
      established a comfort function goal during a routine preoperative patient
      education class. No significant difference in pain score or opiate requirement
      was found for these data. However, a fundamental clinical question arose
      surrounding opiate requirements and dosing management. In our hospital, the norm
      for postoperative pain management is to categorize pain scores as mild (1-3),
      moderate (4-6), and severe (7-10) pain. Physician orders commonly use this
      differential to order opiate dose ranges. In this sample, the mean pain score for
      the intervention group at home is 5.8 and the mean comfort function goal is 4.9.
      Based on normative categories of pain scores, if a patient's baseline of
      tolerable pain is 4.9, this has potential impact on clinician responses to
      managing pain, as 4.9-5.8 is, for this patient, perhaps a mild range of pain, not
      moderate. If a patient reports a pain score of 7, and their norm is 5.8, the
      delta is only 1.2. Does this imply that the patient is experiencing mild or
      severe pain? Does the nurse deliver a dose of pain medication that is in the mild
      or severe dose range? 

PMID- 26293198
TI  - Safety and efficacy of commonly used antiemetics.
AB  - INTRODUCTION: Clinicians use antiemetic drugs in a multitude of scenarios.
      Despite the differences in subspecialty and etiology of the nausea, practitioners
      of all subspecialties use the same drugs in similar ways to provide relief for
      their patients. AREAS COVERED: Multiple classes of antiemetics are used
      frequently but no single treatment course works for all types of patients. The
      complex etiology of nausea often requires a multimodal approach that targets the
      same symptom through different sites of action. Antiemetics have unique side
      effects and safety profiles which are covered in this review. Antihistamines,
      phenothiazines, corticosteroids, benzamindes, anticholinergic, neurokinin-1
      antagonists, 5-HT3 receptor antagonist and cannabinoids are discussed. These
      drugs were evaluated based on an in-depth literature review including a review of
      the original research that led to many of the drugs initial FDA approval, via
      internet and PubMed searches. EXPERT OPINION: The key to providing relief for
      patients suffering from nausea and vomiting is to consider multiple drugs to
      approach the nausea in a systematic way. Anesthesiologists identify patients who
      are at high risk of nausea and vomiting based on physical characteristics and
      surgical procedures. Oncologists treat nausea based on the prescribed
      chemotherapeutics regimen and known risk of emesis while palliative care
      physicians and others balance the etiology of the nausea while optimizing
      patients other co morbid conditions.

PMID- 26293200
TI  - Development of a novel proton dosimetry system using an array of fiber-optic
      Cerenkov radiation sensors.
AB  - This study describes the development and evaluation of a new dosimetric system
      for proton therapy using an array of fiber-optic Cerenkov radiation sensors
      (AFCRS). The AFCRS was superior to a conventional, multi-layer ion chamber (MLIC)
      system in real-time data acquisition and cost effectiveness. 

PMID- 26293199
TI  - Distinct partitioning of ALS associated TDP-43, FUS and SOD1 mutants into
      cellular inclusions.
AB  - Amyotrophic lateral sclerosis is a rapidly progressing neurodegenerative disease
      associated with protein misfolding and aggregation. Most cases are characterized
      by TDP-43 positive inclusions, while a minority of familial ALS cases are instead
      FUS and SOD1 positive respectively. Cells can generate inclusions of variable
      type including previously characterized aggresomes, IPOD or JUNQ structures
      depending on the misfolded protein. SOD1 invariably forms JUNQ inclusions but it
      remains unclear whether other ALS protein aggregates arise as one of these
      previously described inclusion types or form unique structures. Here we show that
      FUS variably partitioned to IPOD, JUNQ or alternate structures, contain a mobile
      fraction, were not microtubule dependent and initially did not contain ubiquitin.
      TDP-43 inclusions formed in a microtubule independent manner, did not contain a
      mobile fraction but variably colocalized to JUNQ inclusions and another alternate
      structure. We conclude that the RNA binding proteins TDP-43 and FUS do not
      consistently fit the currently characterised inclusion models suggesting that
      cells have a larger repertoire for generating inclusions than currently thought,
      and imply that toxicity in ALS does not stem from a particular aggregation
      process or aggregate structure. 

PMID- 26293201
TI  - Prospective surveillance study of haemophilia A patients switching from
      moroctocog alfa or other factor VIII products to moroctocog alfa albumin-free
      cell culture (AF-CC) in usual care settings.
AB  - This prospective, open-label, postauthorisation safety surveillance study
      assessed clinically significant inhibitor development in patients with severe
      haemophilia A transitioning from moroctocog alfa or other factor VIII (FVIII)
      replacement products to reformulated moroctocog alfa (AF-CC). Males aged >= 12
      years with severe haemophilia A (FVIII:C) < 1 IU/dl), > 150 exposure days (EDs)
      to recombinant or plasma-derived FVIII products, and no detectable inhibitor at
      screening were enrolled. Primary end point was the incidence of clinically
      significant FVIII inhibitor development. Secondary end points included annualised
      bleeding rate (ABR), less-than-expected therapeutic effect (LETE), and FVIII
      recovery. Patients were assigned to one of two cohorts based on whether they were
      transitioning to moroctocog alfa (AF-CC) from moroctocog alfa (cohort 1; n=146)
      or from another recombinant or plasma-derived FVIII product (cohort 2; n=62).
      Mean number of EDs on study was 94 (range, 1-139). Six positive FVIII inhibitor
      results, as determined by local laboratories, were reported in four patients;
      none were confirmed by a central laboratory, no inhibitor-related clinical
      manifestations were reported, and all anti-FVIII antibody assays were negative.
      Median ABRs were 23.4 and 3.4 in patients categorised at baseline as following on
      demand and prophylactic regimens, respectively; 86.5% of bleeding episodes
      resolved after one infusion. LETE incidence was 0.06% and 0.19% in the on-demand
      and prophylaxis settings, respectively. FVIII recovery remained constant
      throughout the study. No new safety concerns were identified. This study found no
      increased risk of clinically significant FVIII inhibitor development in patients
      transitioning from moroctocog alfa or other FVIII replacement products to
      moroctocog alfa (AF-CC).

PMID- 26293202
TI  - Oligonucleotides containing a ribo-configured cyclohexanyl nucleoside: probing
      the role of sugar conformation in base pairing selectivity.
AB  - The synthesis and a preliminary evaluation of the pairing properties of ribo
      cyclohexanyl nucleic acids (r-CNA) is herein reported. Incorporation of a single
      r-CNA nucleotide into natural duplexes did not enhance their stability, while a
      very high pairing selectivity for RNA was found. As deduced by comparative
      analysis of Tm and NMR data, a relationship between pairing selectivity and
      conformational preferences of the "sugar" moiety of r-CNA (and more generally of
      six-membered nucleic acids) was suggested. 

PMID- 26293203
TI  - Establishment and genetic characterization of a novel mixed-phenotype acute
      leukemia cell line with EP300-ZNF384 fusion.
AB  - Herein, we describe the establishment and characterization of the first mixed
      phenotype acute leukemia cell line (JIH-5). The JIH-5 cell line was established
      from leukemia cells with B lymphoid/myeloid phenotype from a female mixed
      phenotype acute leukemia patient. JIH-5 cells exhibit an immunophenotype
      comprised of myeloid and B lymphoid antigens. Whole-exome sequencing revealed
      somatic mutations in nine genes in JIH-5 cells. Transcriptional sequencing of JIH
      5 cells identified EP300-ZNF384 fusion transcript, which is a recurrent
      alteration in B cell acute lymphoblastic leukemia. Our results suggest that the
      JIH-5 cell line may serve as a tool for the study of mixed-phenotype acute
      leukemia or EP300-ZNF384. 

PMID- 26293205
TI  - The nature of photogenerated charge separation among different crystal facets of
      BiVO4 studied by density functional theory.
AB  - Charge separation among different crystal facets of a semiconductor has been
      observed experimentally, but the underlying reasons behind this phenomenon are
      unknown. In this work, the activation energies of carrier hopping and the
      mobility of electron/hole transport along seven low-index crystal orientations of
      bulk BiVO4 have been calculated using a small polaron model. The calculated
      mobility and our previous experimental results reveal that there is a parallel
      relationship between the carrier mobility along the crystal axis and the carrier
      preferred accumulation on the corresponding crystal facets. It is proposed that
      the mobility of electrons (or holes) along the crystal axis [hkl] might be
      essentially related to the charge separation among the indices of corresponding
      facets (hkl); namely, the mobility of electrons (or holes) along the crystal axis
      [hkl] is the largest among all possible crystal axes, and the photogenerated
      electrons (or holes) tend to be accumulated on the indices of the corresponding
      facet (hkl) when the surface factors like surface band bending, surface energetic
      differences, etc. are not considered. 

PMID- 26293204
TI  - Enhanced marine sulphur emissions offset global warming and impact rainfall.
AB  - Artificial fertilisation of the ocean has been proposed as a possible
      geoengineering method for removing carbon dioxide from the atmosphere. The
      associated increase in marine primary productivity may lead to an increase in
      emissions of dimethyl sulphide (DMS), the primary source of sulphate aerosol over
      remote ocean regions, potentially causing direct and cloud-related indirect
      aerosol effects on climate. This pathway from ocean fertilisation to aerosol
      induced cooling of the climate may provide a basis for solar radiation management
      (SRM) geoengineering. In this study, we investigate the transient climate impacts
      of two emissions scenarios: an RCP4.5 (Representative Concentration Pathway 4.5)
      control; and an idealised scenario, based on RCP4.5, in which DMS emissions are
      substantially enhanced over ocean areas. We use mini-ensembles of a coupled
      atmosphere-ocean configuration of CESM1(CAM5) (Community Earth System Model
      version 1, with the Community Atmosphere Model version 5). We find that the
      cooling effect associated with enhanced DMS emissions beneficially offsets
      greenhouse gas induced warming across most of the world. However, the rainfall
      response may adversely affect water resources, potentially impacting human
      livelihoods. These results demonstrate that changes in marine phytoplankton
      activity may lead to a mixture of positive and negative impacts on the climate. 

PMID- 26293206
TI  - Acute resolution of pulmonary alveolar infiltrates in 10 dogs with pulmonary
      hypertension treated with sildenafil citrate: 2005-2014.
AB  - OBJECTIVE: To describe clinical canine patients with naturally occurring
      pulmonary hypertension and radiographic pulmonary alveolar infiltrates before and
      after treatment with sildenafil. ANIMALS: Ten client-owned dogs. METHODS: A
      retrospective analysis of dogs with echocardiographically-determined pulmonary
      hypertension and pulmonary alveolar infiltrates on thoracic radiographs was
      performed before (PRE) and after (POST) sildenafil therapy. Clinical scores,
      pulmonary alveolar infiltrate scores and tricuspid regurgitation gradients were
      analyzed PRE and POST sildenafil. RESULTS: Pulmonary alveolar infiltrates
      associated with pulmonary hypertension developed in a diffusely patchy
      distribution (10/10). Sixty percent of dogs had a suspected diagnosis of
      interstitial pulmonary fibrosis as the etiology of pulmonary hypertension. Median
      PRE clinical score was 4 (range: 3-4) compared to POST score of 0 (0-2) (p =
      0.005). Median alveolar infiltrate score PRE was 10 (5-12) compared to POST score
      of 4 (0-6) (p = 0.006). Median tricuspid regurgitation gradient PRE was 83 mmHg
      (57-196) compared to 55 mmHg POST (33-151) (p = 0.002). CONCLUSIONS: A subset of
      dogs with moderate to severe pulmonary hypertension present with diffuse, patchy
      alveolar infiltrates consistent with non-cardiogenic pulmonary edema. The typical
      clinical presentation is acute dyspnea and syncope, often in conjunction with
      heart murmurs suggestive of valvular insufficiency. This constellation of signs
      may lead to an initial misdiagnosis of congestive heart failure or pneumonia;
      however, these dogs clinically and radiographically improve with the initiation
      of sildenafil.

PMID- 26293207
TI  - Developing Quinoidal Fluorophores with Unusually Strong Red/Near-Infrared
      Emission.
AB  - Despite the dominant position of aromatic fluorophores, we report herein the
      design and synthesis of quinoidal fluorophores based on rarely emissive quinoidal
      bithiophene. Quinoidal bitheno[3,4-b]thiophene, QBTT-C6, consisting of cruciform
      fused (E)-1,2-bis(5-hexylthiophen-2-yl)ethene and quinoidal bithiophene, shows a
      fluorescence quantum yield of 8.5%, 25-fold higher than that of the parent
      quinoidal QBT chromophore, but its maximum emission is at similar wavelengths.
      QBTT-Ar's featuring intramolecular charge transfer can further shift the maximum
      emission into the near-infrared region. The intramolecular charge transfer is
      programmably enhanced by tuning the substituents on the aryl groups from the
      electron-withdrawing trifluoromethyl to the electron-donating methoxy groups.
      Unexpectedly, a positive relationship between intramolecular charge transfer and
      fluorescence quantum yield is observed; as a result, QBTT-FL gives an
      unprecedentedly high fluorescence quantum yield of up to 53.1% for quinoidal
      oligothiophenes. With detailed photophysical and theoretical investigations, we
      demonstrate that the nonradiative intersystem crossing (S1 -> T2) is
      significantly restrained in QBTT-Ar's, which can be attributed to the faster
      reverse intersystem crossing (T2 -> S1) characteristic of a small activation
      energy. This work reveals the possibility for developing red/near-infrared
      fluorophores from the less explored quinoidal molecules because of their
      intrinsically narrow bandgaps. 

PMID- 26293208
TI  - Coma associated with nelarabine in an elderly patient with T-cell acute
      lymphoblastic leukemia and severe chronic renal disease.

PMID- 26293210
TI  - Information processing in computer-assisted interventions: 5th international
      conference, 2014.

PMID- 26293209
TI  - Efficient CRISPR/Cas9-mediated biallelic gene disruption and site-specific
      knockin after rapid selection of highly active sgRNAs in pigs.
AB  - Genetic engineering in livestock was greatly enhanced by the emergence of
      clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR
      associated 9 (Cas9), which can be programmed with a single-guide RNA (sgRNA) to
      generate site-specific DNA breaks. However, the uncertainties caused by wide
      variations in sgRNA activity impede the utility of this system in generating
      genetically modified pigs. Here, we described a single blastocyst genotyping
      system to provide a simple and rapid solution to evaluate and compare the sgRNA
      efficiency at inducing indel mutations for a given gene locus. Assessment of
      sgRNA mutagenesis efficiencies can be achieved within 10 days from the design of
      the sgRNA. The most effective sgRNA selected by this system was successfully used
      to induce site-specific insertion through homology-directed repair at a frequency
      exceeding 13%. Additionally, the highly efficient gene deletion via the selected
      sgRNA was confirmed in pig fibroblast cells, which could serve as donor cells for
      somatic cell nuclear transfer. We further showed that direct cytoplasmic
      injection of Cas9 mRNA and the favorable sgRNA into zygotes could generate
      biallelic knockout piglets with an efficiency of up to 100%. Thus, our method
      considerably reduces the uncertainties and expands the practical possibilities of
      CRISPR/Cas9-mediated genome engineering in pigs. 

PMID- 26293211
TI  - Multiscale modeling of tumor growth induced by circadian rhythm disruption in
      epithelial tissue.
AB  - We propose a multiscale chemo-mechanical model of cancer tumor development in
      epithelial tissue. The model is based on the transformation of normal cells into
      a cancerous state triggered by a local failure of spatial synchronization of the
      circadian rhythm. The model includes mechanical interactions and a chemical
      signal exchange between neighboring cells, as well as a division of cells and
      intercalation that allows for modification of the respective parameters following
      transformation into the cancerous state. The numerical simulations reproduce
      different dephasing patterns--spiral waves and quasistationary clustering, with
      the latter being conducive to cancer formation. Modification of mechanical
      properties reproduces a distinct behavior of invasive and localized carcinoma.

PMID- 26293214
TI  - Moisture dipole over the Tibetan Plateau during the past five and a half
      centuries.
AB  - The South Asian Monsoon and mid-latitude Westerlies are two important controls on
      Tibetan Plateau (TP) fresh water resources. Understanding their interaction
      requires long-term information on spatial patterns in moisture variability on the
      TP. Here we develop a network of 23 moisture-sensitive tree-ring chronologies
      from major juniper forests in a north-south transect on the eastern TP. Over the
      past five and a half centuries, we find that these chronologies cluster into two
      groups, North and South, of ~33 degrees  N. Southern and northern regional
      chronology subsets are positively and significantly correlated with May-June
      Palmer Drought Severity Indices (PDSI). The meridional moisture stress gradient
      reconstructed from these data suggests substantial stochastic variation, yet
      persistent moisture stress differences are observed between 1463-1502 CE and 1693
      1734 CE. Identification of these patterns provides clues linking them with forced
      or intrinsic tropical-extratropical interactions and thus facilitates studies of
      interannual-decadal dipole variations in hydroclimate over the TP. 

PMID- 26293213
TI  - The Structure of the Holo-Acyl Carrier Protein of Leishmania major Displays a
      Remarkably Different Phosphopantetheinyl Transferase Binding Interface.
AB  - The genome of Leishmania major encodes a type II fatty acid biosynthesis pathway
      for which no structural or biochemical information exists. Here, for the first
      time, we have characterized the central player of the pathway, the acyl carrier
      protein (LmACP), using nuclear magnetic resonance (NMR). Structurally, the LmACP
      molecule is similar to other type II ACPs, comprising a four-helix bundle,
      enclosing a hydrophobic core. Dissimilarities in sequence, however, exist in
      helix II (recognition helix) of the protein. The enzymatic conversion of apo
      LmACP into the holo form using type I (Escherichia coli AcpS) and type II (Sfp
      type) phosphopantetheinyl transferases (PPTs) is relatively slow. Mutagenesis
      studies underscore the importance of the residues present at the protein-protein
      interaction interface of LmACP in modulating the activity of PPTs. Interestingly,
      the cognate PPT for this ACP, the L. major 4'-phosphopantetheinyl transferase
      (LmPPT), does not show any enzymatic activity toward it, though it readily
      converts other type I and type II ACPs into their holo forms. NMR chemical shift
      perturbation studies suggest a moderately tight complex between LmACP and its
      cognate PPT, suggesting inhibition. We surmise that the unique surface of LmACP
      might have evolved to complement its cognate enzyme (LmPPT), possibly for the
      purpose of regulation. 

PMID- 26293212
TI  - Ivabradine and Bisoprolol on Doppler-derived Coronary Flow Velocity Reserve in
      Patients with Stable Coronary Artery Disease: Beyond the Heart Rate.
AB  - INTRODUCTION: Coronary flow velocity reserve (CFVR) is an important prognostic
      marker in patients with stable coronary artery disease (CAD). Beta-blockers and
      ivabradine have been shown to improve CFVR in patients with stable CAD, but their
      effects were never compared. The aim of the current study was to compare the
      effects of bisoprolol and ivabradine on CFVR in patients with stable CAD.
      METHODS: Patients in sinus rhythm with stable CAD were enrolled in this
      prospective, randomized, double-blind trial. Patients had to be in a stable
      condition for at least 15 days before enrollment, on their usual therapy.
      Patients who were receiving beta-blockers or ivabradine entered a 2-week washout
      period from these drugs before randomization. Transthoracic Doppler-derived CFVR
      was assessed in left anterior descending coronary artery, and was calculated as
      the ratio of hyperemic to baseline diastolic coronary flow velocity (CFV).
      Hyperemic CFV was obtained using dipyridamole administration using standard
      protocols. After CFVR assessment, patients were randomized to ivabradine or
      bisoprolol and entered an up-titration phase, and CFVR was assessed again 1 month
      after the end of the up-titration phase. RESULTS: Fifty-nine patients (38 male,
      21 female; mean age 69 +/- 9 years) were enrolled. Transthoracic Doppler-derived
      assessment of CFV and CFVR was successfully performed in all patients. Baseline
      characteristics were similar between the bisoprolol and ivabradine groups. No
      patient dropped out during the study. At baseline, rest and hyperemic peak CFV as
      well as CFVR was not significantly different in the ivabradine and bisoprolol
      groups. After the therapy, resting peak CFV significantly decreased in both the
      ivabradine and bisoprolol groups, but there was no significant difference between
      the groups (ivabradine group 20.7 +/- 4.6 vs. 22.8 +/- 5.2, P < 0.001; bisoprolol
      group 20.1 +/- 4.1 vs. 22.1 +/- 4.3, P < 0.001). However, hyperemic peak CFV
      significantly increased in both groups, but to a greater extent in patients
      treated with ivabradine (ivabradine: 70.7 +/- 9.4 vs. 58.8 +/- 9.2, P < 0.001;
      bisoprolol: 65 +/- 8.3 vs. 58.7 +/- 8.2, P < 0.001). Accordingly, CFVR
      significantly increased in both groups (ivabradine 3.52 +/- 0.64 vs. 2.67 +/-
      0.55, P < 0.001; bisoprolol 3.35 +/- 0.70 vs. 2.72 +/- 0.55, P < 0.001), but it
      was significantly higher in ivabradine group, despite a similar decrease in heart
      rate (63 +/- 7 vs. 61 +/- 6; P not significant). CONCLUSION: Ivabradine improves
      hyperemic peak CFV and CFVR to a greater extent than bisoprolol in patients with
      stable CAD, despite a similar decrease in heart rate. These data demonstrate that
      the benefits from ivabradine therapy go beyond the heart rate. This could be due
      to a different mechanism such as diastolic perfusion time, isovolumic ventricular
      relaxation, end-diastolic pressure, and collaterals. FUNDING: Servier.

PMID- 26293215
TI  - Mobile phone text message reminders: Measuring preferences of people with
      antipsychotic medication.
AB  - Mobile technology use, including Short Messaging Service (SMS) text messaging,
      has increased in health care services. Preferences regarding the type or timing
      of text messages sent by healthcare providers to people with antipsychotic
      medication have not yet been fully investigated. This study examines the
      relationship between patients' demographic characteristics and the tailored
      messages they select. The study ("Mobile.Net", ISRCTN: 27704027) includes a
      structured analysis of a random sub-sample of participants who received messages
      for 12months. The data were collected in 24 sites and 45 psychiatric hospitals in
      Finland and analyzed with descriptive statistics and Poisson regression models.
      The study sample involved 562 people on antipsychotic medication, and a total of
      2112 text messages (2 to 25 monthly) were analysed. Regarding message content,
      there was no significant variation in the proportions relating to 'medication',
      'treatment appointments' or 'free time'. Monday was the most popular day to
      receive messages and morning was preferred to later in the day. Age was most
      closely associated with 'number of messages' and 'time of messages'. Older women
      and younger men preferred higher numbers of messages (p=0.0031). Participants
      preferred positive, encouraging and slightly humorous messages. The findings
      suggest that messages may be acceptable for difficult to access groups in follow
      up. This type of intervention may be useful for various types of patients
      especially for younger males. To further support the evidence about factors
      related to message utilization and use, it is important to evaluate the
      effectiveness of text messages in psychiatric care.

PMID- 26293216
TI  - Overexpression of SPAG9 in human gastric cancer is correlated with poor
      prognosis.
AB  - Sperm associated antigen 9 (SPAG9) protein has been found to play an important
      role in cancer progression but the involved mechanisms are still obscure. Its
      clinical significance in human gastric cancers remains unexplored. In the present
      study, SPAG9 expression was analyzed in 147 gastric cancer specimens. We observed
      weak staining in normal gastric mucosa and positive staining in 65 out of 147
      (44.2 %) cancer samples. Overexpression of SPAG9 correlated with local invasion
      (p = 0.0101), lymph node metastasis (p = 0.0488), TNM stage (p = 0.0002), and
      relapse (p = 0.0018). Importantly, SPAG9 overexpression correlated with poor
      overall survival (p = 0.0008). Furthermore, we performed siRNA knockdown of SPAG9
      in HGC-27 cells with high endogenous expression and transfected SPAG9 plasmid in
      SGC-7901 cell line with low endogenous level. SPAG9 overexpression promoted while
      its depletion inhibited cell proliferation, cell cycle transition, and invasive
      cell growth. SPAG9 overxpression also increased chemoresistance to 5-
      fluorouracil (5-FU) in SGC-7901 cells. Further analysis showed that SPAG9
      knockdown downregulated and its overexpression upregulated cyclin D1, MMP9, and p
      p38 expression. In conclusion, SPAG9 overexpression in gastric cancer correlates
      with poor prognosis and contributes to gastric cancer cell proliferation,
      invasion, and chemoresistance. SPAG9 promotes gastric cancer invasion, possibly
      through p38-MMP9 signaling pathways.

PMID- 26293218
TI  - Response letter to "What can be more prognostic than the pTNM category assessed
      in radical cystectomy samples?" by Sukosd F, Ivanyi B and Pajor L.

PMID- 26293217
TI  - Expression of miRNAs in adenoid cystic carcinomas of the breast and salivary
      glands.
AB  - Despite their similar histomorphologic appearance, adenoid cystic carcinomas of
      the breast and salivary glands (bACCs and sACCs, respectively) are clinically and
      pathologically diverse. We studied the expression levels of 18 microRNAs (miRNAs)
      in bACCs and sACCs and control normal breast and salivary gland tissues (bNs and
      sNs, respectively) by quantitative real-time polymerase chain reaction on
      formalin-fixed paraffin embedded tissues. miRNAs showing significant differences
      between the study groups were selected for target prediction. Increased
      expression of miR-17 and miR-20a was found in bACCs compared with bNs (p(miR-17)
      = 0.017 and p(miR-20a) = 0.024, respectively), while the expression level of let
      7b and miR-193b was lower in sACCs compared with normal sNs (p let-7b = 0.032 and
      p(miR-193b) = 0.023, respectively). Expression of miR-23b and miR-27b differed
      between normal breast and normal salivary gland tissue (p(miR-23b) = 0.007 and
      p(miR-27b) = 0.024, respectively), but not between bACCs and sACCs. The potential
      target mRNAs CCND1 and BCL2 were identified as reported targets of let-7b, miR
      193b, miR-17, and miR-20a. Expression of their corresponding proteins cyclin D1
      and Bcl-2 was studied by immunohistochemistry. We found both proteins
      overexpressed in bACCs as well as sACCs in comparison with corresponding normal
      tissues. However, expression of cyclin D1 and Bcl-2 proteins was not
      significantly different between bACCs and sACCs or between bNs and sNs. Although
      no differences in miRNA levels were found between bACCs and sACCs, in both
      organs, miRNA expression level was highly different between tumor tissue and
      control tissue.

PMID- 26293219
TI  - [A Study of 2-Mercaptobenzothiazole (2-MBT) and HBM values for 2-MBT in the urine
      of adults and children: Opinion of the "Human Biomonitoring" Commission of the
      German Federal Environment Agency].
AB  - 2-Mercaptobenzothiazole (2-MBT, CAS No. 149-30-4) is mainly used as a
      vulcanization accelerator in the production of rubber. Other applications are as
      a fungicide in paints and varnishs and for the external treatment of animals.
      Because of its manifold application in consumer products, for example in
      soothers, exposure of the general population to 2-MBT can't be excluded. For the
      purpose of a toxicological evaluation of a possible body burden, the German HBM
      commission derived HBM-I values for 2-MBT in the urine of children and adults.
      The no observed adverse effect level of 94 mg/kg bw/d from a subchronic oral
      study with mice was used as the point of departure. After considering a total
      assessment factor of 350, a tolerable daily intake of 0.3 mg/kg bw/d was deduced
      for humans. Considering further the percentage of 2-MBT and its glucuronide
      excreted in urine together with the body weight proportional urine volume leads
      to an HBM-I value for 2-MBT of 4.5 mg/l urine for children and 7 mg/l urine for
      adults.

PMID- 26293220
TI  - [Development of telemedical solutions based on the electronic case record (EFA)].
AB  - Efficient communication among doctors who cooperatively support their patients is
      a prerequisite for implementing effective intersectoral treatment processes. In
      order to achieve this, IT is becoming increasingly important. With IT systems
      doctors want to exchange information concerning a patient's case (e.g. doctors'
      letters, medication prescriptions, etc.). Furthermore, more and more IT-based
      applications that support the treatment process between patient and doctor (e.g.
      telemedicine solutions) are being developed. The development of the electronic
      case record (elektronische FallAkte) has yielded concepts and solutions for a
      structured case-based information exchange. Furthermore, it has led to
      infrastructure solutions that support service-based applications for telemedical
      applications. The "elektronische FallAkte" is an initiative of health
      institutions that have been organized into the association "Verein elektronische
      FallAkte". In this paper, concepts and realizations of the "elektronische
      FallAkte", as well as service-based applications on that infrastructure are
      described. 

PMID- 26293221
TI  - [Telemedicine in Germany].

PMID- 26293222
TI  - One-year Patient-reported Outcomes After Arthroscopic Rotator Cuff Repair Do Not
      Correlate With Mild to Moderate Psychological Distress.
AB  - BACKGROUND: Patients with shoulder and rotator cuff pathology who exhibit greater
      levels of psychological distress report inferior preoperative self-assessments of
      pain and function. In several other areas of orthopaedics, higher levels of
      distress correlate with a higher likelihood of persistent pain and disability
      after recovery from surgery. To our knowledge, the relationship between
      psychological distress and outcomes after arthroscopic rotator cuff repair has
      not been similarly investigated. QUESTIONS/PURPOSES: (1) Are higher levels of
      preoperative psychological distress associated with differences in outcome scores
      (visual analog scale [VAS] for pain, Simple Shoulder Test, and American Shoulder
      and Elbow Surgeons score) 1 year after arthroscopic rotator cuff repair? (2) Are
      higher levels of preoperative psychological distress associated with less
      improvement in outcome scores (VAS for pain, Simple Shoulder Test, and American
      Shoulder and Elbow Surgeons score) 1 year after arthroscopic rotator cuff repair?
      (3) Does the prevalence of psychological distress in a population with full
      thickness rotator cuff tears change when assessed preoperatively and 1 year after
      arthroscopic rotator cuff repair? METHODS: Eighty-five patients with full
      thickness rotator cuff tears were prospectively enrolled; 70 patients (82%) were
      assessed at 1-year followup. During the study period, the three participating
      surgeons performed 269 rotator cuff repairs; in large part, the low overall rate
      of enrollment was related to two surgeons enrolling only two patients total in
      the initial 14 months of the study. Psychological distress was quantified using
      the Distress Risk Assessment Method questionnaire, and patients completed self
      assessments including the VAS for pain, the Simple Shoulder Test, and the
      American Shoulder and Elbow Surgeons score preoperatively and 1 year after
      arthroscopic rotator cuff repair. Fifty of 85 patients (59%) had normal levels of
      distress, 26 of 85 (31%) had moderate levels of distress, and nine of 85 (11%)
      had severe levels of distress. Statistical models were used to assess the effect
      of psychological distress on patient self-assessment of shoulder pain and
      function at 1 year after surgery. RESULTS: With the numbers available, distressed
      patients were not different from nondistressed patients in terms of postoperative
      VAS for pain (1.9 [95% confidence interval {CI}, 1.0-2.8] versus 1.0 [95% CI, 0.5
      1.4], p = 0.10), Simple Shoulder Test (9 [95% CI, 8.1-10.4] versus 11 [95% CI,
      10.0-11.0], p = 0.06), or American Shoulder and Elbow Surgeons scores (80 [95%
      CI, 72-88] versus 88 [95% CI, 84-92], p = 0.08) 1 year after arthroscopic rotator
      cuff repair. With the numbers available, distressed patients also were not
      different from nondistressed patients in terms of the amount of improvement in
      scores between preoperative assessment and 1-year followup on the VAS for pain (3
      [95% CI, 2.2-4.1] versus 2 [95% CI, 1.4-2.9], p = 0.10), Simple Shoulder Test
      (5.2 [95% CI, 3.7-6.6] versus 5.0 [95% CI, 4.2-5.8], p = 0.86), or American
      Shoulder and Elbow Surgeons scale (38 [95% CI, 29-47] versus 30 [95% CI, 25-36],
      p = 0.16). The prevalence of psychological distress in our patient population was
      lower at 1 year after surgery 14 of 70 (20%) versus 35 of 85 (41%) preoperatively
      (odds ratio, 0.36; 95% CI, 0.17-0.74; p = 0.005). CONCLUSIONS: Mild to moderate
      levels of distress did not diminish patient-reported outcomes to a clinically
      important degree in this small series of patients with rotator cuff tears. This
      contrasts with reports from other areas of orthopaedic surgery and may be related
      to a more self-limited course of symptoms in patients with rotator cuff disease
      or possibly to a beneficial effect of rotator cuff repair on sleep quality or
      other unrecognized determinants of psychosocial status. LEVEL OF EVIDENCE: Level
      I, prognostic study.

PMID- 26293223
TI  - CORR Insights((r)): Otto Aufranc Award: Large Heads Do Not Increase Damage at the
      Head-neck Taper of Metal-on-polyethylene Total Hip Arthroplasties.

PMID- 26293224
TI  - CORR Insights((r)): Regional Intraosseous Administration of Prophylactic
      Antibiotics is More Effective Than Systemic Administration in a Mouse Model of
      TKA.

PMID- 26293225
TI  - Correction to "Three-Step Synthesis of Ethyl Canthinone-3-carboxylates from Ethyl
      4-Bromo-6-methoxy-1,5-naphthyridine-3-carboxylate via a Pd-Catalyzed Suzuki
      Miyaura Coupling and a Cu-Catalyzed Amidation Reaction".

PMID- 26293226
TI  - CoMOGrad and PHOG: From Computer Vision to Fast and Accurate Protein Tertiary
      Structure Retrieval.
AB  - The number of entries in a structural database of proteins is increasing day by
      day. Methods for retrieving protein tertiary structures from such a large
      database have turn out to be the key to comparative analysis of structures that
      plays an important role to understand proteins and their functions. In this
      paper, we present fast and accurate methods for the retrieval of proteins having
      tertiary structures similar to a query protein from a large database. Our
      proposed methods borrow ideas from the field of computer vision. The speed and
      accuracy of our methods come from the two newly introduced features- the co
      occurrence matrix of the oriented gradient and pyramid histogram of oriented
      gradient- and the use of Euclidean distance as the distance measure. Experimental
      results clearly indicate the superiority of our approach in both running time and
      accuracy. Our method is readily available for use from this website:
      http://research.buet.ac.bd:8080/Comograd/. 

PMID- 26293227
TI  - A basic model for training of microscopic and endoscopic transsphenoidal
      pituitary surgery: the Egghead.
AB  - BACKGROUND: Transsphenoidal endoscopic surgery has gained popularity in the last
      2 decades and is becoming a standard technique for resection of pituitary
      adenomas. In contrast to their ENT colleagues, neurosurgical residents have
      practically no endoscopic experience when they reach the training stage for
      transsphenoidal procedures. We have developed an affordable method for repetitive
      training in endoscopic (and microscopic) work in a narrow channel, allowing
      training of the basic movements needed for resection of pituitary adenoma.
      METHODS: In collaboration with colleagues in the ENT Department, Cantonal
      Hospital St. Gall, and the Technical University of Zurich, a three-dimensional
      model of the nasal cavity was developed and patented. The Egghead model consists
      of a 3D synthetic reconstruction of the head nasal cavity and sphenoid sinus. A
      boiled egg represents the sella. For validation, 17 neurosurgical residents from
      the Department of Neurosurgery, University Hospital of Basel, and Department of
      Neurosurgery, Cantonal Hospital of St. Gall, St. Gall, Switzerland, and two
      experts performed a standardized procedure mimicking a transsphenoidal pituitary
      procedure by dissecting a corridor to the egg yolk and resecting it, respecting
      the surrounding egg white. This procedure was performed under both microscopic
      and video-endoscopic visualization. A score for the precision and speed of the
      surgical performance was developed and used. RESULTS: The model allows repetitive
      training of the resection of the egg yolk under sparing of the egg white after
      careful opening of the shell. The validation data showed a steeper learning curve
      using the endoscopic technique than performing the same task using the
      microscope. After three repetitions, the quality of resection was better with the
      endoscopic technique. CONCLUSIONS: Our model, the Egghead, is affordable, offers
      tactile feedback and allows infinite repetitions in basic training for pituitary
      surgery. It can be used for training of advanced neurosurgical residents, who
      thus far have very few possibilities of acquiring endoscopic experience.

PMID- 26293228
TI  - Intraforaminal ozone therapy and particular side effects: preliminary results and
      early warning.
AB  - BACKGROUND: The term "low back pain syndrome" represents a complex nosological
      entity. The therapeutic approach is often only symptomatic and not etiologic.
      METHODS: Since 2013, 186 patients (97 males and 89 females, mean age 59.8 years)
      have undergone microsurgery for lumbar disc hernia or lumbar segmental stenosis.
      Among these patients, 23 had been previously treated with ozone therapy by the
      intraforaminal approach and 28 by intraforaminal steroid injections in other
      hospitals between 12 and 24 months before our clinical evaluation. These patients
      received 16 applications in an 8-week period (standard therapy). RESULTS: During
      the surgery, many hard adhesions between the soft tissues and bony structures
      were unexpectedly discovered. In particular, it was noted that the root
      contracted and had firm adhesions to the dural sac and/or fragmented disc, which
      were difficult to resolve. These specific pathological patterns were observed
      only in the patients who received ozone injections by the intraforaminal
      approach. We did not find any pathological abnormalities in the patients who did
      not receive any injections or who received intraforaminal steroid injections.
      Thus, we could exclude that the tissue damage was due to the mechanical action of
      the needle. CONCLUSION: It is important to assert that ozone therapy procedures
      can be associated with several major complications. Therefore, performing a
      revision of the guidelines and protocols for ozone therapy application is
      indispensable.

PMID- 26293230
TI  - Consultants will have seven day rotas by 2020, government says in response to
      open letter.

PMID- 26293229
TI  - Coronary artery visibility in free-breathing young children on non-gated chest
      CT: impact of temporal resolution.
AB  - BACKGROUND: Dual-source CT allows scanning of the chest with high pitch and high
      temporal resolution, which can improve the detection of proximal coronary
      arteries in infants and young children when scanned without general anesthesia,
      sedation or beta-blockade. OBJECTIVE: To compare coronary artery visibility
      between higher and standard temporal resolution. MATERIALS AND METHODS: We
      analyzed CT images in 93 children who underwent a standard chest CT angiographic
      examination with reconstruction of images with a temporal resolution of 75 ms
      (group 1) and 140 ms (group 2). RESULTS: The percentage of detected coronary
      segments was higher in group 1 than in group 2 when considering all segments
      (group 1: 27%; group 2: 24%; P = 0.0004) and proximal segments (group 1: 37%;
      group 2: 32%; P = 0.0006). In both groups, the highest rates of detection were
      observed for the left main coronary artery (S1) (group 1: 65%; group 2: 58%) and
      proximal left anterior descending coronary artery (S2) (group 1: 43%; group 2:
      42%). Higher rates of detection were seen in group 1 for the left main coronary
      artery (P = 0.03), proximal right coronary artery (P = 0.01), proximal segments
      of the left coronary artery (P = 0.02) and proximal segments of the left and
      right coronary arteries (P = 0.0006). CONCLUSION: Higher temporal resolution
      improved the visibility of proximal coronary arteries in pediatric chest CT.

PMID- 26293231
TI  - Adenovirus 36 DNA in human adipose tissue.
AB  - Recent studies have suggested a possible correlation between obesity and
      adenovirus 36 (Adv36) infection in humans. As information on adenoviral DNA
      presence in human adipose tissue are limited, we evaluated the presence of Adv36
      DNA in adipose tissue of 21 adult overweight or obese patients. Total DNA was
      extracted from adipose tissue biopsies. Virus detection was performed using PCR
      protocols with primers against specific Adv36 fiber protein and the viral
      oncogenic E4orf1 protein nucleotide sequences. Sequences were aligned with the
      NCBI database and phylogenetic analyses were carried out with MEGA6 software.
      Adv36 DNA was found in four samples (19%). This study indicates that some
      individuals carry Adv36 in the visceral adipose tissue. Further studies are
      needed to determine the specific effect of Adv36 infection on adipocytes, the
      prevalence of Adv36 infection and its relationship with obesity in the
      perspective of developing a vaccine that could potentially prevent or mitigate
      infection. 

PMID- 26293232
TI  - The role of fatness on physical fitness in adolescents with and without Down
      syndrome: The UP&DOWN study.
AB  - BACKGROUND/OBJECTIVES: Adolescents with Down syndrome (DS) exhibit higher levels
      of fatness and low levels of physical fitness compared with those without DS. In
      adolescents without DS, fatness is tightly associated with physical fitness, but
      this association is unclear in adolescents with DS. The aim of this study was to
      examine the association between several markers of fatness and physical fitness
      in a relative large sample of adolescents with and without DS. SUBJECTS/METHODS:
      A total of 111 adolescents with DS (41 females) aged 11-20 years participated in
      this cross-sectional study. We also included a sex-matched control group (ratio
      1:2) of 222 adolescents without DS aged 12-18 years, participating in the UP&DOWN
      Study. The Assessing Level of Physical Activity (ALPHA) health-related fitness
      test battery for adolescents was used to assess fatness and physical fitness.
      RESULTS: Our results show that fatness is not associated with low levels of
      physical fitness in adolescents with DS (that is, 3 of the 16 analyses identified
      differences in physical fitness variables by groups of fatness). In contrast,
      fatness, as expected, is associated with levels of physical fitness in
      adolescents without DS (that is, 13 of the 16 analyses identified differences in
      physical fitness variables by groups of fatness). CONCLUSIONS: The present
      finding contributes to new knowledge by suggesting that the role of fatness on
      physical fitness is different in adolescents with and without DS, and
      consequently, the poor levels of physical fitness in adolescents with DS may be
      due to the syndrome rather than the high prevalence of obesity from this
      population.

PMID- 26293234
TI  - Nutritional quality and child-oriented marketing of breakfast cereals in
      Guatemala.
AB  - OBJECTIVES: Food marketing has been implicated as an important driver of obesity.
      However, few studies have examined food marketing in low- and middle-income
      countries (LMICs). This study documents the prevalence of advertising on cereal
      boxes in Guatemala and examines associations between various marketing strategies
      and nutritional quality. METHODS: One box from all available cereals was
      purchased from a supermarket located in an urban area in Guatemala City,
      Guatemala. A content analysis was performed to document child-oriented marketing
      practices, product claims and health-evoking images. The Nutrient Profile Model
      (NPM) was used to calculate an overall nutrition score for each cereal (the
      higher the score, the lower the nutritional quality). RESULTS: In all, 106
      cereals were purchased, and half of the cereals featured child-oriented marketing
      (54, 50.9%). Cereals had a mean (+/-s.d.) of 5.10+/-2.83 product claims per
      cereal, and most cereals (102, 96.2%) contained health-evoking images. Child
      oriented cereals had, on average, higher NPM scores (13.0+/-0.55 versus 7.90+/
      0.74, P<0.001) and sugar content (10.1+/-0.48 versus 6.19+/-0.50 g/30 g, P<0.001)
      compared with non-child oriented cereals. Cereals with health claims were not
      significantly healthier than those without claims. CONCLUSIONS: In Guatemala,
      cereals targeting children were generally of poor nutritional quality. Cereals
      displaying health claims were also not healthier than those without such claims.
      Our findings support the need for regulations restricting the use of child
      oriented marketing and health claims for certain products.

PMID- 26293235
TI  - Management of Cardiovascular Risk in Patients with Chronic Inflammatory Diseases:
      Current Evidence and Future Perspectives.
AB  - An increased risk of cardiovascular disease (CVD) has been observed in a range of
      chronic inflammatory diseases (CID), including rheumatoid arthritis (RA),
      psoriasis, inflammatory bowel diseases (IBD), and systemic lupus erythematosus
      (SLE). The increased risk of CVDs and reduced life expectancy in these conditions
      has stimulated considerable research and started an ongoing discussion on the
      need for a multidisciplinary approach and dedicated guidelines on CVD prevention
      in these patients. In addition, the possibility of inhibiting inflammation as a
      means to preventing CVD in these patients has gained considerable interest in
      recent years. We briefly summarize the current level of evidence of the
      association between CIDs and CVD and cardiovascular risk management
      recommendations. Perspectives of ongoing and planned trials are discussed in
      consideration of potential ways to improve primary and secondary CVD prevention
      in patients with CID. 

PMID- 26293233
TI  - Little appetite for obesity: meta-analysis of the effects of maternal obesogenic
      diets on offspring food intake and body mass in rodents.
AB  - BACKGROUND: There is increasing recognition that maternal effects contribute to
      variation in individual food intake and metabolism. For example, many
      experimental studies on model animals have reported the effect of a maternal
      obesogenic diet during pregnancy on the appetite of offspring. However, the
      consistency of effects and the causes of variation among studies remain poorly
      understood. METHODS: After a systematic search for relevant publications, we
      selected 53 studies on rats and mice for a meta-analysis. We extracted and
      analysed data on the differences in food intake and body weight between offspring
      of dams fed obesogenic diets and dams fed standard diets during gestation. We
      used meta-regression to study predictors of the strength and direction of the
      effect sizes. RESULTS: We found that experimental offspring tended to eat more
      than control offspring but this difference was small and not statistically
      significant (0.198, 95% highest posterior density (HPD)=-0.118-0.627). However,
      offspring from dams on obesogenic diets were significantly heavier than offspring
      of control dams (0.591, 95% HPD=0.052-1.056). Meta-regression analysis revealed
      no significant influences of tested predictor variables (for example, use of
      choice vs no-choice maternal diet, offspring sex) on differences in offspring
      appetite. Dietary manipulations that extended into lactation had the largest
      effect on body weight. Subgroup analysis revealed that high protein to non
      protein ratio of the maternal diet may promote increased body weight in
      experimental offspring in comparison with control offspring; low protein content
      in the maternal chow can have opposite effect. CONCLUSIONS: Exposure to maternal
      obesogenic diets in early life is not likely to result in a substantial change in
      offspring appetite. Nevertheless, we found an effect on offspring body weight,
      consistent with permanent alterations of offspring metabolism in response to
      maternal diet. Additionally, it appears that protein content of the obesogenic
      diet and timing of manipulation modulate the effects on offspring body weight in
      later life.

PMID- 26293236
TI  - Comment on: "pharmacokinetics and tolerability of the novel oral prostacyclin IP
      receptor agonist selexipag".

PMID- 26293237
TI  - Authors' reply to Srinivas: "pharmacokinetics and tolerability of the novel oral
      prostacyclin IP receptor agonist selexipag".

PMID- 26293239
TI  - Oxygen Evolution Catalyzed by Nickel-Iron Oxide Nanocrystals with a
      Nonequilibrium Phase.
AB  - Mixed nickel-iron oxides are of great interest as electrocatalysts for the oxygen
      evolution reaction (OER), the kinetically challenging half-reaction required for
      the generation of hydrogen gas from water via electrolysis. Previously, we had
      reported the synthesis of single crystal, soluble nickel-iron oxide nanoparticles
      over a wide range of nickel:iron compositions, with a metastable cubic rock salt
      phase ([Ni,Fe]O) that can be isolated despite the low solubility of iron in cubic
      nickel oxide at ambient temperatures. Here, activity for OER was examined,
      catalyzed by these [Ni,Fe]O nanoparticles integrated with indium tin oxide (ITO)
      electrodes. Because the as-prepared [Ni,Fe]O nanoparticles are oleate-capped, the
      surface ligands needed to be removed to induce adherence to the ITO substrate,
      and to enable charge transfer and contact with water to enable OER catalysis. Two
      different approaches were taken to reduce or eliminate the coverage of oleate
      ligands in these films: UV irradiation (254 nm) and air plasma. UV irradiation
      proved to lead to better results in terms of stable and OER-active films at pH
      13. Kinetic analysis revealed that the Tafel slopes of these nanoparticle
      [Ni,Fe]O OER electrodes were limited by the electrochemical surface area and were
      found to be within the range of 30 to 50 mV/decade. Across the four compositions
      of Ni:Fe studied, from 24:76 to 88:12, the observed overpotential at 10 mA/cm2
      for the OER in basic conditions decreased from 0.47 to 0.30 V as the proportion
      of nickel increased from 24% to 88%.

PMID- 26293238
TI  - Designing and implementing a socioeconomic intervention to enhance TB control:
      operational evidence from the CRESIPT project in Peru.
AB  - BACKGROUND: Cash transfers are key interventions in the World Health
      Organisation's post-2015 global TB policy. However, evidence guiding TB-specific
      cash transfer implementation is limited. We designed, implemented and refined a
      novel TB-specific socioeconomic intervention that included cash transfers, which
      aimed to support TB prevention and cure in resource-constrained shantytowns in
      Lima, Peru for: the Community Randomized Evaluation of a Socioeconomic
      Intervention to Prevent TB (CRESIPT) project. METHODS: Newly-diagnosed TB
      patients from study-site healthposts were eligible to receive the intervention
      consisting of economic and social support. Economic support was provided to
      patient households through cash transfers on meeting the following conditions:
      screening for TB in household contacts and MDR TB in patients; adhering to TB
      treatment and chemoprophylaxis; and engaging with CRESIPT social support
      (household visits and community meetings). To evaluate project acceptability,
      quantitative and qualitative feedback was collected using a mixed-methods
      approach during formative activities. Formative activities included
      consultations, focus group discussions and questionnaires conducted with the
      project team, project participants, civil society and stakeholders. RESULTS: Over
      7 months, 135 randomly-selected patients and their 647 household contacts were
      recruited from 32 impoverished shantytown communities. Of 1299 potential cash
      transfers, 964 (74 %) were achieved, 259 (19 %) were not achieved, and 76 (7 %)
      were yet to be achieved. Of those achieved, 885/964 (92 %) were achieved
      optimally and 79/964 (8 %) sub-optimally. Key project successes were identified
      during 135 formative activities and included: strong multi-sectorial
      collaboration; generation of new evidence for TB-specific cash transfer; and the
      project being perceived as patient-centred and empowering. Challenges included:
      participant confidence being eroded through cash transfer delays, hidden account
      charges and stigma; access to the initial bank-provider being limited; and
      conditions requiring participation of all TB-affected household members (e.g.
      community meetings) being hard to achieve. Refinements were made to improve
      project acceptability and future impact: the initial bank-provider was changed;
      conditional and unconditional cash transfers were combined; cash transfer sums
      were increased to a locally-appropriate, evidence-based amount; and cash transfer
      size varied according to patient household size to maximally reduce mitigation of
      TB-related costs and be more responsive to household needs. CONCLUSIONS: A novel
      TB-specific socioeconomic intervention including conditional cash transfers has
      been designed, implemented, refined and is ready for impact assessment, including
      by the CRESIPT project. The lessons learnt during this research will inform
      policy-makers and decision-makers for future implementation of related
      interventions.

PMID- 26293240
TI  - Television watching and colorectal cancer survival in men.
AB  - PURPOSE: To assess the association between pre- and postdiagnostic time spent
      sitting watching TV as well as other sedentary behaviors (other sitting at home
      and at work/driving) and mortality from colorectal cancer or other causes, and
      overall mortality. METHODS: We followed stage I-III colorectal cancer patients
      from the Health Professionals Follow-up Study (1986-2010). Cox models were used
      to calculate hazard ratios (HRs) and 95 % confidence intervals (CIs). RESULTS: A
      total of 926 and 714 patients were included in the analysis of pre- and
      postdiagnostic TV watching, respectively, and 471 and 325 died during follow-up.
      Prolonged prediagnostic TV viewing was associated with increased risk of
      colorectal cancer-specific mortality independent of leisure-time physical
      activity. The HRs (95 % CIs) for 0-6, 7-13, 14-20, and >=21 h/week were 1.00
      (referent), 0.84 (0.56-1.25), 1.15 (0.75-1.78), and 2.13 (1.31-3.45) (p trend =
      0.01). The association was observed primarily among overweight and obese
      individuals. Prediagnostic TV watching was also associated with overall mortality
      within 5 years of diagnosis, largely due to the association with colorectal
      cancer mortality. Other prediagnostic sitting at home or at work/driving was not
      associated with mortality. Postdiagnostic TV viewing was associated with a
      nonsignificantly increased risk of colorectal cancer-specific mortality (HR for
      >=21 vs 0-6 h/week = 1.45; 95 % CI 0.73-2.87) adjusting for TV viewing before
      diagnosis. CONCLUSION: Prolonged prediagnostic TV watching is associated with
      higher colorectal cancer-specific mortality independent of leisure-time physical
      activity among colorectal cancer patients.

PMID- 26293242
TI  - Rare fibrolipoma of the tongue: a case report.
AB  - INTRODUCTION: Lipoma is a benign tumor infrequent in the oral cavity,
      particularly in the tongue: indeed, lipomas only represent approximately 0.3% of
      all tongue neoplasia. Compared to conventional lipoma, fibrolipoma of the tongue
      is a very rare lesion that accounts for around 25-40% of tongue lipomas, and
      until now, to the best of our knowledge, only 14 cases have been described in
      which histological diagnosis of fibrolipoma was specifically confirmed. We report
      the case of a patient with a voluminous fibrolipoma of the tongue, treated by
      means of surgical excision. Fibrolipoma excision, like that described in this
      report, sometimes may be laborious, because fibrous bands appear to be focally
      infiltrating adjacent tissues, giving rise to some doubts about the nature of the
      lesion. CASE PRESENTATION: We report the case of a voluminous fibrolipoma of the
      tongue in a 71-year-old Caucasian woman. CONCLUSIONS: Because of its histological
      characteristics, abundance of connective and secondary changes/atrophy,
      fibrolipoma may appear as infiltrating adjacent tissues and may cause doubts of
      differential diagnosis with malignant infiltrating lesions. Surgical excision is
      the elective treatment. However, an accurate differential diagnosis, postsurgical
      histological examination and careful follow-up are required.

PMID- 26293243
TI  - The Effect of ADAM8 on the Proliferation and Apoptosis of Hepatocytes and
      Hepatoma Carcinoma Cells.
AB  - This study was undertaken to evaluate the effect of ADAM8 on the proliferation
      and apoptosis of hepatocytes and hepatoma carcinoma cells during hepatocellular
      carcinoma (HCC) progression. The expression of ADAM8 was significantly increased
      with good correlation of PCNA expression increasing and cells apoptosis
      decreasing during the progression of HCC in the liver of mice. Proliferation
      experiment in vitro showed that recombinant ADAM8 could induce the expression of
      PCNA in L02 cells, but not in HepG2 cells. Apoptosis experiment in vitro showed
      that recombinant ADAM8 did not induce or inhibit the expression of apoptosis
      related factors Bcl2, Bax, and Caspase3 in L02 cells, but significantly induced
      the expression of Bcl2, inhibited the expression of Bax and Caspase3 in HepG2
      cells. In conclusion, our study suggested that ADAM8 could promote the
      proliferation of normal hepatocytes and render hepatoma carcinoma cells more
      resistant to apoptosis to play important roles during the progression of HCC.
      ADAM8; Proliferation; Apoptosis.

PMID- 26293241
TI  - Exposure to environmental chemicals and heavy metals, and risk of pancreatic
      cancer.
AB  - PURPOSE: Exposure to various chemicals and heavy metals has been associated with
      risk of different cancers; however, data on whether such exposures may increase
      the risk of pancreatic cancer (PC) are very limited and inconclusive. We examined
      PC risk with self-reported exposures to chemicals and heavy metals. METHODS: The
      design was a clinic-based, case-control study of data collected from 2000 to 2014
      at Mayo Clinic in Rochester, Minnesota, USA. Cases were rapidly ascertained
      patients diagnosed with pancreatic ductal adenocarcinoma (n = 2,092). Controls
      were cancer-free patients in primary care clinics (n = 2,353), frequency-matched
      to cases on age, race, sex, and state/region of residence. Cases and controls
      completed identical risk factor questionnaires, which included yes/no questions
      about regular exposure to pesticides, asbestos, benzene, chlorinated
      hydrocarbons, chromium, and nickel. Unconditional logistic regression was used to
      estimate odds ratios (ORs) and 95% confidence intervals (CI) comparing those who
      affirmed exposure to each of the chemicals/heavy metals to those who reported no
      regular exposure, adjusting for potential confounders. RESULTS: Self-reported
      regular exposure to pesticides was associated with increased odds of PC (OR 1.21,
      95% CI 1.02-1.44). Regular exposure to asbestos (OR 1.54, 95% CI 1.23-1.92),
      benzene (OR 1.70, 95% CI 1.23-2.35), and chlorinated hydrocarbons (OR 1.63, 95%
      CI 1.32-2.02) also was associated with higher odds of PC. Chromium and nickel
      exposures were not significantly associated with PC. CONCLUSIONS: These findings
      add to the limited data suggesting that exposure to pesticides, asbestos,
      benzene, and chlorinated hydrocarbons may increase PC risk. They further support
      the importance of implementing strategies that reduce exposure to these
      substances.

PMID- 26293244
TI  - Cyclic Polymer with Alternating Monomer Sequence.
AB  - Cyclic polymers with alternating monomer sequence are synthesized for the first
      time based on the ring-closure strategy. Well-defined telechelic alternating
      polymers are synthesized by reversible addition-fragmentation chain transfer
      polymerization by copolymerizing the electron acceptor monomer of N
      benzylmaleimide and donor monomer of styrene with a feed ratio of 1 between them.
      The corresponding cyclic alternating polymers are then produced by the UV-induced
      Diels-Alder click reaction to ring-close the linear alternating polymer
      precursors under highly diluted reaction solution. 

PMID- 26293245
TI  - Evidence for seasonal reproduction in UK domestic cats.
AB  - OBJECTIVES: The aims of this study were to analyse a large body of data obtained
      by the Royal Society for the Prevention of Cruelty to Animals (RSPCA) Greater
      Manchester Animal Hospital on the breeding pattern of owned domestic cats in the
      UK, and to provide clear statistical evidence of whether seasonal variation
      remains present in temperate climates. METHODS: The total number of cats spayed
      and the number of cats found to be pregnant were recorded on a monthly basis from
      December 2005 to July 2014 by the RSPCA Greater Manchester Animal Hospital. The
      percentage of cats found to be pregnant was calculated for each month and the 8.5
      years of data were binned into calendar months. The mean and SD of the monthly
      pregnancy rate was calculated for each calendar month bin, as was the difference
      between the mean percentage of detected pregnancies and the global mean. The Z
      score for each month's difference was then calculated. RESULTS: Data were
      available for 5414 cats neutered during the 8.5 consecutive years of this study.
      A global average of 8.9% of cats spayed were found to be pregnant. The mean
      calendar month pregnancy rate exhibited a very significant variation, with the
      highest positive deviation being in April (Z score +2.9) and the highest negative
      deviation being in November/December (Z score -4.5). When aggregated into 3 month
      averages, an extremely significant difference between 'spring' and 'winter'
      months of >7 SE (P <<0.01) was found. CONCLUSIONS AND RELEVANCE: This study
      provides clear statistical evidence, from a large data set, that seasonal
      breeding patterns are still present under UK temperate conditions. We discuss the
      impact that this has on charity rescue shelters and propose that a campaign
      targeted at clients of animal welfare charities encouraging autumn neutering will
      be the most cost-effective method of cat population control, and help relieve the
      demand on welfare charity resources.

PMID- 26293246
TI  - Limited Proteolysis Combined with Stable Isotope Labeling Reveals Conformational
      Changes in Protein (Pseudo)kinases upon Binding Small Molecules.
AB  - Likely due to conformational rearrangements, small molecule inhibitors may
      stabilize the active conformation of protein kinases and paradoxically promote
      tumorigenesis. We combined limited proteolysis with stable isotope labeling MS to
      monitor protein conformational changes upon binding of small molecules. Applying
      this method to the human serine/threonine kinase B-Raf, frequently mutated in
      cancer, we found that binding of ATP or its nonhydrolyzable analogue AMP-PNP, but
      not ADP, stabilized the structure of both B-Raf(WT) and B-Raf(V600E). The ATP
      competitive type I B-Raf inhibitor vemurafenib and the type II inhibitor
      sorafenib stabilized the kinase domain (KD) but had distinct effects on the Ras
      binding domain. Stabilization of the B-Raf(WT) KD was confirmed by
      hydrogen/deuterium exchange MS and molecular dynamics simulations. Our results
      are further supported by cellular assays in which we assessed cell viability and
      phosphorylation profiles in cells expressing B-Raf(WT) or B-Raf(V600E) in
      response to vemurafenib or sorafenib. Our data indicate that an overall
      stabilization of the B-Raf structure by specific inhibitors activates MAPK
      signaling and increases cell survival, helping to explain clinical treatment
      failure. We also applied our method to monitor conformational changes upon
      nucleotide binding of the pseudokinase KSR1, which holds high potential for
      inhibition in human diseases. 

PMID- 26293247
TI  - Determinants of emergency response responsibility perceptions in the local public
      health workforce after China's health sector restructuring.
AB  - BACKGROUND: Local health departments are the backbone of public health emergency
      (PHE) response plans. The front line of emergency response preparedness is
      people. Role perceptions of individual staff members of a given organization
      strongly affect response probability and performance. Therefore, the aim of this
      study was to determine local public health employees' perceptions of emergency
      response responsibilities, identify factors that influence their perception, and
      indicate the challenges and bottlenecks of PHE response in the Health Inspection
      Institution (HII) after its separation from China's multiple Centers for Disease
      Control and Prevention (CDC). METHODS: We used a stratified randomized sample
      survey to examine HII workers' knowledge of their own duties concerning PHE
      response in 17 facilities in Heilongjiang, a province in northeastern China. Data
      were collected from May to July 2010 using a 9-item combined question inquiring
      about the workers' statutory duties. RESULTS: Of 348 administered surveys, 309
      were returned for an overall response rate of 88.8%. Overall, the correct
      recognition rate of PHE responsibilities was low. Some HII workers were confused
      about their responsibilities required by law, regulations, and emergency response
      plans. A quarter of all the respondents had the lowest knowledge for PHE
      responsibilities. Factors influencing their perceptions of responsibilities were
      department, work experience in a CDC, and PHE response experience. CONCLUSIONS:
      To improve preparedness for a PHE, efforts are needed to train, support, and
      monitor the workers' knowledge and competencies in PHEs as part of an
      organizational change; the worker's knowledge of their responsibilities should be
      measured and used as an indicator of preparedness for a PHE, and training should
      be undertaken where there are deficiencies. Management should also encourage
      workers in the departments of food hygiene/school health surveillance to be more
      involved in PHE preparedness and response issues.

PMID- 26293288
TI  - Recombinant osteoprotegerin effects during orthodontic movement in a rat model.
AB  - BACKGROUND AND OBJECTIVES: Anchorage is one of the most challenging sides in
      orthodontics. The use of biological modulators that inhibit osteoclasts could be
      a solution to address these problems and provide new adjunctive approaches. The
      aim of this study was to assess the effectiveness of recombinant osteoprotegerin
      fusion protein (OPG-Fc) in orthodontic anchorage. MATERIALS AND METHODS: Two
      groups of male Sprague-Dawley rats were utilized. The animals in the experimental
      group received twice-weekly injections with high dose of OPG-Fc (5.0mg/kg) in
      mesial and distal mucosa of the first molars, and those in the control group
      received no drugs. Right first maxillary molars were mesialized using a
      calibrated nickel-titanium spring connected to an anterior mini-screw. Tooth
      movement was measured by two blinded observers using scanned and magnified stone
      casts. Receptor activator of nuclear factor kappaB (RANK), run-related
      transcription factor 2 (Runx2), type I collagen, vimentin, matrix
      metalloproteinases 2 and 9, S100 protein and the putative mechanoproteins acid
      sensing ion channel (ASIC2) and transient receptor potential vainilloid 4 (TRPV4)
      were evaluated using immunohistochemistry. RESULTS: OPG-Fc group showed an
      important decreased in mesial molar movement with only 52%, 31%, and 22% of the
      total mesial molar movement compared with control group at Days 7, 14, and 21,
      respectively (P < 0.001). RANK ligand and Runx2 positive cells were severely
      reduced after OPG-Fc treatment. Periodontal ligament architecture, cell
      arrangement, and immunohistochemical patter for vimentin, type I collagen and the
      mechanoproteins TRPV4 and ASIC2 were altered by tooth movement and all these
      parameters altered by the applied treatment. CONCLUSIONS: OPG-Fc effectively
      inhibits osteoclastogenesis resulting in improved bone quantity and orthodontic
      anchorage. Based on present results, OPG-Fc could have clinical utility in
      preventing undesired tooth movements.

PMID- 26293290
TI  - Temporally divergent significant meanings, biographical disruption and self
      management for chronic joint pain.
AB  - Self-management is recommended by policy and clinical guidelines as a way to
      contend with the growing incidence of osteoarthritis-related joint pain in an
      ageing population. Sociologists assert that self-management is as much about lay
      strategies for dealing with the biographically disruptive qualities of chronic
      illness as opposed to solely complying with medical regimens. The original
      concept of biographical disruption coined by Bury is not uncontested. Chronic
      joint pain has been characterised as featuring 'co-existing meanings' of
      significance and consequence. The former conferring no biographical disruption
      due to osteoarthritis being associated with 'normal ageing' and the latter
      causing biographical disruption due to the corporeal limitations joint pain
      imparts, which, in turn, can influence whether, why and how self-management is
      undertaken. This article reports findings from repeat interviews and a diary
      study completed by 22 participants with chronic knee pain. We explore the co
      existing but temporally divergent 'meanings as significance' associated with knee
      pain. Participants describe the onset and current experience of the pain in terms
      of biographical normality (retrospective or contemporaneous meanings). Future
      meanings as significance are mediated by cultural beliefs about ageing and
      current physical consequences of the condition, and also have a distinct
      character of their own. Knee pain is associated with the possibility of
      disability and harbours a distinct risk; potential disruption to everyday social
      relationships, notably relating to care and dependency. In turn, future meanings
      of significance influence the preventative self-management strategies that people
      utilise. We argue for a more cogent theoretical understanding of temporal
      dimensions of biographical disruption, biographical work and subsequent self
      management by utilising and extending the thought of Bury, and Corbin and
      Strauss. Doing so helps to understand patient self-management strategies and
      facilitates self-management support in clinical settings for osteoarthritis and
      potentially other chronic conditions.

PMID- 26293291
TI  - Promoter-specific regulation of PPARGC1A gene expression in human skeletal
      muscle.
AB  - The goal of this study was to identify unknown transcription start sites of the
      PPARGC1A (PGC-1alpha) gene in human skeletal muscle and investigate the promoter
      specific regulation of PGC-1alpha gene expression in human skeletal muscle. Ten
      amateur endurance-trained athletes performed high- and low-intensity exercise
      sessions (70  min, 70% or 50% o2max). High-throughput RNA sequencing and exon
      exon junction mapping were applied to analyse muscle samples obtained at rest and
      after exercise. PGC-1alpha promoter-specific expression and activation of
      regulators of PGC-1alpha gene expression (AMPK, p38 MAPK, CaMKII, PKA and CREB1)
      after exercise were evaluated using qPCR and western blot. Our study has
      demonstrated that during post-exercise recovery, human skeletal muscle expresses
      the PGC-1alpha gene via two promoters only. As previously described, the
      additional exon 7a that contains a stop codon was found in all samples.
      Importantly, only minor levels of other splice site variants were found (and not
      in all samples). Constitutive expression PGC-1alpha gene occurs via the canonical
      promoter, independent of exercise intensity and exercise-induced increase of
      AMPK(Thr172) phosphorylation level. Expression of PGC-1alpha gene via the
      alternative promoter is increased of two orders after exercise. This post
      exercise expression is highly dependent on the intensity of exercise. There is an
      apparent association between expression via the alternative promoter and
      activation of CREB1.

PMID- 26293289
TI  - Retroviral integration: Site matters: Mechanisms and consequences of retroviral
      integration site selection.
AB  - Here, we review genomic target site selection during retroviral integration as a
      multistep process in which specific biases are introduced at each level. The
      first asymmetries are introduced when the virus takes a specific route into the
      nucleus. Next, by co-opting distinct host cofactors, the integration machinery is
      guided to particular chromatin contexts. As the viral integrase captures a local
      target nucleosome, specific contacts introduce fine-grained biases in the
      integration site distribution. In vivo, the established population of proviruses
      is subject to both positive and negative selection, thereby continuously
      reshaping the integration site distribution. By affecting stochastic proviral
      expression as well as the mutagenic potential of the virus, integration site
      choice may be an inherent part of the evolutionary strategies used by different
      retroviruses to maximise reproductive success. 

PMID- 26293292
TI  - A 2-cycle audit on the feasibility, efficacy and patient acceptance of 21
      emergency sphenopalatine artery ligations under local anaesthesia: Our
      Experience.

PMID- 26293294
TI  - Review of integrase strand transfer inhibitors for the treatment of human
      immunodeficiency virus infection.
AB  - Integrase strand transfer inhibitors (INSTIs) are oral antiretroviral agents used
      against HIV infection. There are three agents available, including raltegravir,
      elvitegravir and dolutegravir, some of which are available as combination
      medications with other antiretroviral drugs. The efficacy and safety of INSTIs in
      treatment-naive and experienced HIV-infected patients have been established by
      multiple studies. Based on the current practice guidelines, INSTI-based regimens
      are considered as one of the first-line therapies for treatment-naive HIV
      infected patients. There are new INSTIs in development to improve the resistance
      profile and to decrease the frequency of drug administration. 

PMID- 26293293
TI  - Four Degrees of Separation: Social Contacts and Health Providers Influence the
      Steps to Final Diagnosis of Active Tuberculosis Patients in Urban Uganda.
AB  - BACKGROUND: Delay in tuberculosis (TB) diagnosis adversely affects patients'
      outcomes and prolongs transmission in the community. The influence of social
      contacts on steps taken by active pulmonary TB patients to seek a diagnosis has
      not been well examined. METHODS: A retrospective study design was use to enroll
      TB patients on treatment for 3 months or less and aged >=18 years from 3 public
      clinics in Kampala, Uganda, from March to July 2014. Social network analysis was
      used to collect information about social contacts and health providers visited by
      patients to measure the number of steps and time between onset of symptoms and
      final diagnosis of TB. RESULTS: Of 294 TB patients, 58 % were male and median age
      was 30 (IQR: 24-38) years. The median number of steps was 4 (IQR: 3, 7)
      corresponding to 70 (IQR: 28,140) days to diagnosis. New patients had more steps
      and time to diagnosis compared retreatment patients (5 vs. 3, P < 0.0001; 84 vs.
      46 days P < 0.0001). Fifty-eight percent of patients first contacted persons in
      their social network. The first step to initiate seeking care accounted for 41 %
      of the patients' time to diagnosis while visits to non-TB providers and TB
      providers (without a TB diagnosis) accounted for 34 % and 11 % respectively. New
      TB patients vs. retreatment (HR: 0.66, 95 % CI; 1.11, 1.99), those who first
      contacted a non-TB health provider vs. contacting social network (HR: 0.72 95 %
      CI; 0.55, 0.95) and HIV seronegative vs. seropositive patients (HR: 0.70, 95 %
      CI; 0.53, 0.92) had a significantly lower likelihood of a timely final diagnosis.
      CONCLUSIONS: There were four degrees of separation between the onset of symptoms
      in a TB patient and a final diagnosis. Both social and provider networks of
      patients influenced the diagnostic pathways. Most delays occurred in the first
      step which represents decisions to seek help, and through interactions with non
      TB health providers. TB control programs should strengthen education and active
      screening in the community and in health care settings to ensure timely diagnosis
      of TB.

PMID- 26293295
TI  - Single newborn screen or routine second screening for primary congenital
      hypothyroidism.
AB  - Routine second screening of most newborns at 8-14 days of life for a panel of
      newborn conditions occurs in 12 U.S. states, while newborns in the other states
      typically undergo only a single routine newborn screen. The study objective was
      to evaluate screening consequences for primary congenital hypothyroidism (CH) in
      one- and two-screen states according to laboratory practices and medical or
      biochemical characteristics of screen-positive cases. Individual-level medical
      and biochemical data were retrospectively collected and analyzed for 2251 primary
      CH cases in one-screen (CA, WI) and two-screen (AL, DE, MD, OR, TX) states.
      Aggregate data were collected and analyzed for medical and biochemical
      characteristics of all screened newborns in the states. Among the states
      evaluated in this study, the detection rate of primary CH was higher in the one
      screen states. In the two-screen states, 11.5% of cases were detected on the
      second screen. In multivariate analyses, only race/ethnicity was a significant
      predictor of cases identified on the first versus second screen, which likely
      reflects a physiologic difference in primary CH presentation. Newborn screening
      programs must heed the potential for newborns with CH not being detected by a
      single screen, particularly newborns of certain races/ethnicities. If the two
      screen states converted to a single screen using their current algorithms,
      newborns currently identified on the routine second screen would presumably not
      be detected, resulting in probable delayed diagnosis and treatment. However,
      based on the one-screen state experiences, with appropriate modifications in
      screening method and algorithm, the two-screen states might convert to single
      screen operation for CH without loss in performance.

PMID- 26293296
TI  - What triggers colour change? Effects of background colour and temperature on the
      development of an alpine grasshopper.
AB  - BACKGROUND: Colour polymorphisms are a fascinating facet of many natural
      populations of plants and animals, and the selective processes that maintain such
      variation are as relevant as the processes which promote their development.
      Orthoptera, the insect group that encompasses grasshoppers and bush crickets,
      includes a particularly large number of species that are colour polymorphic with
      a marked green-brown polymorphism being particularly widespread. Colour
      polymorphism has been associated with the need for crypsis and background
      matching and background-dependent homochromy has been described in a few species.
      However, when and how different environmental conditions influence variation in
      colour remains poorly understood. Here we test for effects of background colour
      and ambient temperature on the occurrence of colour morph switches (green to
      brown or brown to green) and developmental darkening in the alpine dwelling club
      legged grasshopper Gomphocerus sibiricus. RESULTS: We monitored individually
      housed nymphae across three of their four developmental stages and into the first
      week after final ecdysis. Our data show an absence of colour morph switches in G.
      sibiricus, without a single switch observed in our sample. Furthermore, we test
      for an effect of temperature on colouration by manipulating radiant heat, a
      limiting factor in alpine habitats. Radiant heat had a significant effect on
      developmental darkening: individuals under low radiant heat tended to darken,
      while individuals under high radiant heat tended to lighten within nymphal
      stages. Young imagoes darkened under either condition. CONCLUSIONS: Our results
      indicate a plastic response to a variable temperature and indicate that melanin,
      a multipurpose pigment responsible for dark colouration and presumed to be
      costly, seems to be strategically allocated according to the current
      environmental conditions. Unlike other orthopterans, the species is apparently
      unable to switch colour morphs (green/brown) during development, suggesting that
      colour morphs are determined genetically (or very early during development) and
      that other processes have to contribute to crypsis and homochromy in this
      species.

PMID- 26293297
TI  - Topical steroid therapy induces pro-tolerogenic changes in Langerhans cells in
      human skin.
AB  - We have investigated the efficacy of conditioning skin Langerhans cells (LCs)
      with agents to promote tolerance and reduce inflammation, with the goal of
      improving the outcomes of antigen-specific immunotherapy. Topical treatments were
      assessed ex vivo, using excised human breast skin maintained in organ bath
      cultures, and in vivo in healthy volunteers by analysing skin biopsies and
      epidermal blister roof samples. Following topical treatment with a
      corticosteroid, tumour necrosis factor-alpha levels were reduced in skin biopsy
      studies and blister fluid samples. Blister fluid concentrations of monocyte
      chemoattractant protein-1, macrophage inflammatory proteins -1alpha and 1beta and
      interferon-gamma inducible protein-10 were also reduced, while preserving levels
      of interleukin-1alpha (IL-1alpha), IL-6, IL-8 and IL-10. Steroid pre-treatment of
      the skin reduced the ability of LCs to induce proliferation, while supernatants
      showed an increase in the IL-10/interferon-gamma ratio. Phenotypic changes
      following topical steroid treatment were also observed, including reduced
      expression of CD83 and CD86 in blister-derived LCs, but preservation of the
      tolerogenic signalling molecules immunoglobulin-like transcript 3 and programmed
      death-1. Reduced expression of HLA-DR, CD80 and CD86 were also apparent in LCs
      derived from excised human skin. Topical therapy with a vitamin D analogue
      (calcipotriol) and steroid, calcipotriol alone or vitamin A elicited no
      significant changes in the parameters studied. These experiments suggest that pre
      conditioning the skin with topical corticosteroid can modulate LCs by blunting
      their pro-inflammatory signals and potentially enhancing tolerance. We suggest
      that such modulation before antigen-specific immunotherapy might provide an
      inexpensive and safe adjunct to current approaches to treat autoimmune diseases.

PMID- 26293298
TI  - A direct fate exclusion mechanism by Sonic hedgehog-regulated transcriptional
      repressors.
AB  - Sonic hedgehog (Shh) signaling patterns the vertebrate spinal cord by activating
      a group of transcriptional repressors in distinct neural progenitors of somatic
      motor neuron and interneuron subtypes. To identify the action of this network, we
      performed a genome-wide analysis of the regulatory actions of three key ventral
      determinants in mammalian neural tube patterning: Nkx2.2, Nkx6.1 and Olig2.
      Previous studies have demonstrated that each factor acts predominantly as a
      transcriptional repressor, at least in part, to inhibit alternative progenitor
      fate choices. Here, we reveal broad and direct repression of multiple alternative
      fates as a general mechanism of repressor action. Additionally, the repressor
      network targets multiple Shh signaling components providing negative feedback to
      ongoing Shh signaling. Analysis of chromatin organization around Nkx2.2-, Nkx6.1-
      and Olig2-bound regions, together with co-analysis of engagement of the
      transcriptional activator Sox2, indicate that repressors bind to, and probably
      modulate the action of, neural enhancers. Together, the data suggest a model for
      neural progenitor specification downstream of Shh signaling, in which Nkx2.2 and
      Olig2 direct repression of alternative neural progenitor fate determinants, an
      action augmented by the overlapping activity of Nkx6.1 in each cell type.
      Integration of repressor and activator inputs, notably activator inputs mediated
      by Sox2, is probably a key mechanism in achieving cell type-specific
      transcriptional outcomes in mammalian neural progenitor fate specification. 

PMID- 26293299
TI  - An Nfic-hedgehog signaling cascade regulates tooth root development.
AB  - Coordination between the Hertwig's epithelial root sheath (HERS) and apical
      papilla (AP) is crucial for proper tooth root development. The hedgehog (Hh)
      signaling pathway and Nfic are both involved in tooth root development; however,
      their relationship has yet to be elucidated. Here, we establish a timecourse of
      mouse molar root development by histological staining of sections, and we
      demonstrate that Hh signaling is active before and during root development in the
      AP and HERS using Gli1 reporter mice. The proper pattern of Hh signaling activity
      in the AP is crucial for the proliferation of dental mesenchymal cells, because
      either inhibition with Hh inhibitors or constitutive activation of Hh signaling
      activity in transgenic mice leads to decreased proliferation in the AP and
      shorter roots. Moreover, Hh activity is elevated in Nfic(-/-) mice, a root defect
      model, whereas RNA sequencing and in situ hybridization show that the Hh
      attenuator Hhip is downregulated. ChIP and RNAscope analyses suggest that Nfic
      binds to the promoter region of Hhip. Treatment of Nfic(-/-) mice with Hh
      inhibitor partially restores cell proliferation, AP growth and root development.
      Taken together, our results demonstrate that an Nfic-Hhip-Hh signaling pathway is
      crucial for apical papilla growth and proper root formation. This discovery
      provides insight into the molecular mechanisms regulating tooth root development.

PMID- 26293300
TI  - Defining the three cell lineages of the human blastocyst by single-cell RNA-seq.
AB  - Here, we provide fundamental insights into early human development by single-cell
      RNA-sequencing of human and mouse preimplantation embryos. We elucidate conserved
      transcriptional programs along with those that are human specific. Importantly,
      we validate our RNA-sequencing findings at the protein level, which further
      reveals differences in human and mouse embryo gene expression. For example, we
      identify several genes exclusively expressed in the human pluripotent epiblast,
      including the transcription factor KLF17. Key components of the TGF-beta
      signalling pathway, including NODAL, GDF3, TGFBR1/ALK5, LEFTY1, SMAD2, SMAD4 and
      TDGF1, are also enriched in the human epiblast. Intriguingly, inhibition of TGF
      beta signalling abrogates NANOG expression in human epiblast cells, consistent
      with a requirement for this pathway in pluripotency. Although the key
      trophectoderm factors Id2, Elf5 and Eomes are exclusively localized to this
      lineage in the mouse, the human orthologues are either absent or expressed in
      alternative lineages. Importantly, we also identify genes with conserved
      expression dynamics, including Foxa2/FOXA2, which we show is restricted to the
      primitive endoderm in both human and mouse embryos. Comparison of the human
      epiblast to existing embryonic stem cells (hESCs) reveals conservation of
      pluripotency but also additional pathways more enriched in hESCs. Our analysis
      highlights significant differences in human preimplantation development compared
      with mouse and provides a molecular blueprint to understand human embryogenesis
      and its relationship to stem cells. 

PMID- 26293301
TI  - Control of vertebrate core planar cell polarity protein localization and dynamics
      by Prickle 2.
AB  - Planar cell polarity (PCP) is a ubiquitous property of animal tissues and is
      essential for morphogenesis and homeostasis. In most cases, this fundamental
      property is governed by a deeply conserved set of 'core PCP' proteins, which
      includes the transmembrane proteins Van Gogh-like (Vangl) and Frizzled (Fzd), as
      well as the cytoplasmic effectors Prickle (Pk) and Dishevelled (Dvl). Asymmetric
      localization of these proteins is thought to be central to their function, and
      understanding the dynamics of these proteins is an important challenge in
      developmental biology. Among the processes that are organized by the core PCP
      proteins is the directional beating of cilia, such as those in the vertebrate
      node, airway and brain. Here, we exploit the live imaging capabilities of Xenopus
      to chart the progressive asymmetric localization of fluorescent reporters of
      Dvl1, Pk2 and Vangl1 in a planar polarized ciliated epithelium. Using this
      system, we also characterize the influence of Pk2 on the asymmetric dynamics of
      Vangl1 at the cell cortex, and we define regions of Pk2 that control its own
      localization and those impacting Vangl1. Finally, our data reveal a striking
      uncoupling of Vangl1 and Dvl1 asymmetry. This study advances our understanding of
      conserved PCP protein functions and also establishes a rapid, tractable platform
      to facilitate future in vivo studies of vertebrate PCP protein dynamics. 

PMID- 26293303
TI  - FOXF1 inhibits hematopoietic lineage commitment during early mesoderm
      specification.
AB  - The molecular mechanisms orchestrating early mesoderm specification are still
      poorly understood. In particular, how alternate cell fate decisions are regulated
      in nascent mesoderm remains mostly unknown. In the present study, we investigated
      both in vitro in differentiating embryonic stem cells, and in vivo in
      gastrulating embryos, the lineage specification of early mesodermal precursors
      expressing or not the Forkhead transcription factor FOXF1. Our data revealed that
      FOXF1-expressing mesoderm is derived from FLK1(+) progenitors and that in vitro
      this transcription factor is expressed in smooth muscle and transiently in
      endothelial lineages, but not in hematopoietic cells. In gastrulating embryos,
      FOXF1 marks most extra-embryonic mesoderm derivatives including the chorion, the
      allantois, the amnion and a subset of endothelial cells. Similarly to the in
      vitro situation, FOXF1 expression is excluded from the blood islands and blood
      cells. Further analysis revealed an inverse correlation between hematopoietic
      potential and FOXF1 expression in vivo with increased commitment toward primitive
      erythropoiesis in Foxf1-deficient embryos, whereas FOXF1-enforced expression in
      vitro was shown to repress hematopoiesis. Altogether, our data establish that
      during gastrulation, FOXF1 marks all posterior primitive streak extra-embryonic
      mesoderm derivatives with the remarkable exception of the blood lineage. Our
      study further suggests that this transcription factor is implicated in actively
      restraining the specification of mesodermal progenitors to hematopoiesis. 

PMID- 26293302
TI  - Arabidopsis HECATE genes function in phytohormone control during gynoecium
      development.
AB  - The fruit, which develops from the fertilised gynoecium formed in the innermost
      whorl of the flower, is the reproductive organ and one of the most complex
      structures of an angiosperm plant. Phytohormones play important roles during
      flower and fruit patterning, morphogenesis and growth, and there is emerging
      evidence for a cross-talk between different classes of plant hormones throughout
      these processes. Here, we show that the bHLH transcription factors HECATE 1
      (HEC1), HEC2 and HEC3, which have previously been identified as essential
      components of transmitting tract formation, affect both auxin and cytokinin
      responses during reproductive tissue development. We find that HEC1 interacts
      with SPATULA (SPT) to control carpel fusion and that both transcription factors
      restrict sensitivity to cytokinin in the gynoecium. In addition, HEC1 is tightly
      integrated into the auxin-signalling network at the levels of biosynthesis,
      transport and transcriptional response. Based on this data, we propose that HEC1
      acts as a local modulator of auxin and cytokinin responses to control gynoecium
      development in Arabidopsis. 

PMID- 26293304
TI  - Ttk69 acts as a master repressor of enteroendocrine cell specification in
      Drosophila intestinal stem cell lineages.
AB  - In adult Drosophila midgut, intestinal stem cells (ISCs) periodically produce
      progenitor cells that undergo a binary fate choice determined primarily by the
      levels of Notch activity that they receive, before terminally differentiating
      into enterocytes (ECs) or enteroendocrine (EE) cells. Here we identified Ttk69, a
      BTB domain-containing transcriptional repressor, as a master repressor of EE cell
      specification in the ISC lineages. Depletion of ttk69 in progenitor cells induced
      ISC proliferation and caused all committed progenitor cells to adopt EE fate,
      leading to the production of supernumerary EE cells in the intestinal epithelium.
      Conversely, forced expression of Ttk69 in progenitor cells was sufficient to
      prevent EE cell specification. The expression of Ttk69 was not regulated by Notch
      signaling, and forced activation of Notch, which is sufficient to induce EC
      specification of normal progenitor cells, failed to prevent EE cell specification
      of Ttk69-depleted progenitors. Loss of Ttk69 led to derepression of the acheate
      scute complex (AS-C) genes scute and asense, which then induced prospero
      expression to promote EE cell specification. These studies suggest that Ttk69
      functions in parallel with Notch signaling and acts as a master repressor of EE
      cell specification in Drosophila ISC lineages primarily by suppressing AS-C
      genes. 

PMID- 26293307
TI  - Noncanonical roles for Tropomyosin during myogenesis.
AB  - For skeletal muscle to produce movement, individual myofibers must form stable
      contacts with tendon cells and then assemble sarcomeres. The myofiber precursor
      is the nascent myotube, and during myogenesis the myotube completes guided
      elongation to reach its target tendons. Unlike the well-studied events of
      myogenesis, such as myoblast specification and myoblast fusion, the molecules
      that regulate myotube elongation are largely unknown. In Drosophila, hoi polloi
      (hoip) encodes a highly conserved RNA-binding protein and hoip mutant embryos are
      largely paralytic due to defects in myotube elongation and sarcomeric protein
      expression. We used the hoip mutant background as a platform to identify novel
      regulators of myogenesis, and uncovered surprising developmental functions for
      the sarcomeric protein Tropomyosin 2 (Tm2). We have identified Hoip-responsive
      sequences in the coding region of the Tm2 mRNA that are essential for Tm2 protein
      expression in developing myotubes. Tm2 overexpression rescued the hoip myogenic
      phenotype by promoting F-actin assembly at the myotube leading edge, by restoring
      the expression of additional sarcomeric RNAs, and by promoting myoblast fusion.
      Embryos that lack Tm2 also showed reduced sarcomeric protein expression, and
      embryos that expressed a gain-of-function Tm2 allele showed both fusion and
      elongation defects. Tropomyosin therefore dictates fundamental steps of
      myogenesis prior to regulating contraction in the sarcomere. 

PMID- 26293305
TI  - Coordinate post-transcriptional repression of Dpp-dependent transcription factors
      attenuates signal range during development.
AB  - Precise control of the range of signalling molecule action is crucial for correct
      cell fate patterning during development. For example, Drosophila ovarian germline
      stem cells (GSCs) are maintained by exquisitely short-range BMP signalling from
      the niche. In the absence of BMP signalling, one GSC daughter differentiates into
      a cystoblast (CB) and this fate is stabilised by Brain tumour (Brat) and Pumilio
      (Pum)-mediated post-transcriptional repression of mRNAs, including that encoding
      the Dpp transducer, Mad. However, the identity of other repressed mRNAs and the
      mechanism of post-transcriptional repression are currently unknown. Here, we
      identify the Medea and schnurri mRNAs, which encode transcriptional regulators
      required for activation and/or repression of Dpp target genes, as additional Pum
      Brat targets, suggesting that tripartite repression of the transducers is
      deployed to desensitise the CB to Dpp. In addition, we show that repression by
      Pum-Brat requires recruitment of the CCR4 and Pop2 deadenylases, with knockdown
      of deadenylases in vivo giving rise to ectopic GSCs. Consistent with this, Pum
      Brat repression leads to poly(A) tail shortening and mRNA degradation in tissue
      culture cells, and we detect a reduced number of Mad and shn transcripts in the
      CB relative to the GSC based on single molecule mRNA quantitation. Finally, we
      show generality of the mechanism by demonstrating that Brat also attenuates pMad
      and Dpp signalling range in the early embryo. Together our data serve as a
      platform for understanding how post-transcriptional repression restricts
      interpretation of BMPs and other cell signals in order to allow robust cell fate
      patterning during development. 

PMID- 26293309
TI  - Patterns of activity adaptation in humeral trabecular bone in Neolithic humans
      and present-day people.
AB  - OBJECTIVE: The annual turnover rate of trabecular bone by far exceeds that of
      cortical bone and, therefore, is very sensitive to its daily loading regime. Here
      we test the hypothesis that the study of the trabecular bone architecture of the
      human humerus is able to differentiate between different habitual manual
      activities. MATERIALS AND METHODS: For this purpose, we compared the trabecular
      architecture of the humeral head in a Neolithic population to that of a sample of
      contemporary Europeans using micro-computed tomography (microCT). We defined in
      each specimen a spherical volume of interest with a diameter of 57.5 +/- 2.5% of
      the maximal diameter of the humeral head to metrically analyze the bulk of
      humeral head trabecular architecture. We subsequently quantified the trabecular
      architectures in the VOIs, measuring seven standard 3D-morphometric parameters,
      and used univariate and multivariate statistical analyses for comparisons within
      and between populations. RESULTS: Univariate statistical analysis showed
      significant differences in a combination of 3D-morphometric parameters. A
      principal components analysis of the 3D-morphometrics of the trabecular
      architectures separated the Neolithic from the contemporary samples on the basis
      of differences in their gross trabecular architecture, including differences in
      the bone volume fraction (BV/TV), the number of trabeculae per unit length (Tb
      N), and the distance between trabeculae (Tb Sp). DISCUSSION: We interpret the
      significant differences found in the humeral trabecular bone of the Neolithic and
      the contemporary group as likely reflecting the distinct manual working routines.
      The trabecular bone configuration in the Neolithic sample shows presumably
      functional signatures of prehistoric subsistence techniques and activity levels.

PMID- 26293308
TI  - Immunohistochemical analysis of hippocampal butyrylcholinesterase: Implications
      for regional vulnerability in Alzheimer's disease.
AB  - Studies of acetylcholine degrading enzymes acetylcholinesterase (AChE) and
      butyrylcholinesterase (BChE) in Alzheimer's disease (AD) have suggested their
      potential role in the development of fibrillar amyloid-beta (Abeta) plaques
      (amyloid plaques). A recent genome-wide association study analysis identified a
      novel association between genetic variations in the BCHE locus and amyloid
      burden. We studied BChE immunoreactivity in hippocampal tissue sections from AD
      and control cases, and examined its relationship with amyloid plaques,
      neurofibrillary tangles (NFT), dystrophic neurites (DN) and neuropil threads
      (NT). Compared to controls, AD cases had greater BChE immunoreactivity in
      hippocampal neurons and neuropils in CA2/3, but not in the CA1, CA4 and dentate
      gyrus. The majority of amyloid plaques (> 80%, using a pan-amyloid marker X-34)
      contained discrete neuritic clusters which were dual-labeled with antibodies
      against BChE and phosphorylated tau (clone AT8). There was no association between
      overall regional BChE immunoreaction intensity and amyloid plaque burden. In
      contrast to previous reports, BChE was localized in only a fraction (~10%) of
      classic NFT (positive for X-34). A similar proportion of BChE-immunoreactive
      pyramidal cells were AT8 immunoreactive. Greater NFT and DN loads were associated
      with greater BChE immunoreaction intensity in CA2/3, but not in CA1, CA4 and
      dentate gyrus. Our results demonstrate that in AD hippocampus, BChE accumulates
      in neurons and plaque-associated neuritic clusters, but only in a small
      proportion of NFT. The association between greater neurofibrillary pathology
      burden and markedly increased BChE immunoreactivity, observed selectively in
      CA2/3 region, could reflect a novel compensatory mechanism. Since CA2/3 is
      generally considered more resistant to AD pathology, BChE upregulation could
      impact the cholinergic modulation of glutamate neurotransmission to
      prevent/reduce neuronal excitotoxicity in AD hippocampus. 

PMID- 26293306
TI  - The receptor tyrosine kinase Pvr promotes tissue closure by coordinating corpse
      removal and epidermal zippering.
AB  - A leading cause of human birth defects is the incomplete fusion of tissues, often
      manifested in the palate, heart or neural tube. To investigate the molecular
      control of tissue fusion, embryonic dorsal closure and pupal thorax closure in
      Drosophila are useful experimental models. We find that Pvr mutants have defects
      in dorsal midline closure with incomplete amnioserosa internalization and
      epidermal zippering, as well as cardia bifida. These defects are relatively mild
      in comparison to those seen with other signaling mutants, such as in the JNK
      pathway, and we demonstrate that JNK signaling is not perturbed by altering Pvr
      receptor tyrosine kinase activity. Rather, modulation of Pvr levels in the
      ectoderm has an impact on PIP3 membrane accumulation, consistent with a link to
      PI3K signal transduction. Polarized PI3K activity influences protrusive activity
      from the epidermal leading edge and the protrusion area changes in accord with
      Pvr signaling intensity, providing a possible mechanism to explain Pvr mutant
      phenotypes. Tissue-specific rescue experiments indicate a partial requirement in
      epithelial tissue, but confirm the essential role of Pvr in hemocytes for
      embryonic survival. Taken together, we argue that inefficient removal of the
      internalizing amnioserosa tissue by mutant hemocytes coupled with impaired
      midline zippering of mutant epithelium creates a situation in some embryos
      whereby dorsal midline closure is incomplete. Based on these observations, we
      suggest that efferocytosis (corpse clearance) could contribute to proper tissue
      closure and thus might underlie some congenital birth defects. 

PMID- 26293310
TI  - Developing nanocrystals for cancer treatment.
AB  - Nanocrystals are carrier-free solid drug particles that are sized in the
      nanometer range and have crystalline characteristics. Due to high drug loading
      (as high as 100%) - free of organic solvents or solubilizing chemicals -
      nanocrystals have become attractive in the field of drug delivery for cancer
      treatment. Top-down and bottom-up approaches have been developed for preparing
      anticancer nanocrystals. In this review, preparation methods and in vivo
      performance of anticancer nanocrystals are discussed first, followed by an
      introduction of hybrid nanocrystals in cancer theranostics. 

PMID- 26293311
TI  - Gardening gone awry: Aberrant spine pruning disrupts long-range networks.

PMID- 26293312
TI  - Possible association between Takotsubo cardiomyopathy, sepsis, and diabetes
      mellitus: a still open question.

PMID- 26293313
TI  - Uncovering the Role of Metal Catalysis in Tetrazole Formation by an In Situ
      Cycloaddition Reaction: An Experimental Approach.
AB  - Using an experimental approach, the role of metal catalysis has been investigated
      in the in situ cycloaddition reaction of nitrile with azide to form tetrazoles.
      It has been shown that metal catalysis serves to activate the cyano group in the
      nitrile reagent by a coordinative interaction.

PMID- 26293314
TI  - The importance of botanical treatments in traditional societies and challenges in
      developing countries.
AB  - Epilepsy is one of the most common neurological conditions worldwide, with many
      affected persons found in Asia, Latin America, and sub-Saharan Africa. Relatedly,
      the large majority found in these regions does not receive the appropriate
      therapy with antiepileptic drugs (AEDs), stemming from various reasons among
      which are lack of access to AEDs, social stigma, and negative cultural attitudes.
      The presence of epilepsy resistant to the available AEDs coupled with the
      frequent AED side effects has further fueled the widespread and growing use of
      botanicals as alternative therapy in several traditional societies in these
      developing countries since people with epilepsy (PWE) consider them as safe and
      effective. There have, however, been few botanicals that have been examined for
      their pharmacological activities related to traditional uses, and there is hardly
      any conclusive evidence regarding their efficacy in humans or knowledge about the
      exact mechanism(s) of action. This review discusses some botanical treatments
      that have been used for epilepsy in developing countries and the challenges
      faced. This article is part of a Special Issue entitled "Botanicals for
      Epilepsy". 

PMID- 26293316
TI  - Percutaneous tibial nerve stimulation in faecal incontinence.

PMID- 26293315
TI  - Percutaneous tibial nerve stimulation versus sham electrical stimulation for the
      treatment of faecal incontinence in adults (CONFIDeNT): a double-blind,
      multicentre, pragmatic, parallel-group, randomised controlled trial.
AB  - BACKGROUND: Percutaneous tibial nerve stimulation (PTNS) is a new ambulatory
      therapy for faecal incontinence. Data from case series suggest it has beneficial
      outcomes in 50-80% patients; however its effectiveness against sham electrical
      stimulation has not been investigated. We therefore aimed to assess the short
      term efficacy of PTNS against sham electrical stimulation in adults with faecal
      incontinence. METHODS: We did a double-blind, multicentre, pragmatic, parallel
      group, randomised controlled trial (CONtrol of Faecal Incontinence using Distal
      NeuromodulaTion [CONFIDeNT]) in 17 specialist hospital units in the UK that had
      the skills to manage patients with faecal incontinence. Eligible participants
      aged 18 years or older with substantial faecal incontinence for whom conservative
      treatments (such as dietary changes and pelvic floor exercises) had not worked,
      were randomly assigned (1:1) to receive either PTNS (via the Urgent PC
      neuromodulation system) or sham stimulation (via a transcutaneous electrical
      nerve stimulation machine to the lateral forefoot) once per week for 12 weeks.
      Randomisation was done with permuted block sizes of two, four, and six, and was
      stratified by sex and then by centre for women. Patients and outcome assessors
      were both masked to treatment allocation for the 14-week duration of the trial
      (but investigators giving the treatment were not masked). The primary outcome was
      a clinical response to treatment, which we defined as a 50% or greater reduction
      in episodes of faecal incontinence per week. We assessed this outcome after 12
      treatment sessions, using data from patients' bowel diaries. Analysis was by
      intention to treat, and missing data were multiply imputed. This trial is
      registered with the ISRCTN registry, number 88559475, and is closed to new
      participants. FINDINGS: Between Jan 23, 2012, and Oct 31, 2013, we randomly
      assigned 227 eligible patients (of 373 screened) to receive either PTNS (n=115)
      or sham stimulation (n=112). 12 patients withdrew from the trial: seven from the
      PTNS group and five from the sham group (mainly because they could not commit to
      receiving treatment every week). Two patients (one in each group) withdrew
      because of an adverse event that was unrelated to treatment (exacerbation of
      fibromyalgia and rectal bleeding). 39 (38%) of 103 patients with full data from
      bowel diaries in the PTNS group had a 50% or greater reduction in the number of
      episodes of faecal incontinence per week compared with 32 (31%) of 102 patients
      in the sham group (adjusted odds ratio 1.28, 95% CI 0.72-2.28; p=0.396). No
      serious adverse events related to treatment were reported in the trial. Seven
      mild, related adverse events were reported in each treatment group, mainly pain
      at the needle site (four in PTNS, three in sham). INTERPRETATION: PTNS given for
      12 weeks did not confer significant clinical benefit over sham electrical
      stimulation in the treatment of adults with faecal incontinence. Further studies
      are warranted to determine its efficacy in the long term, and in patient
      subgroups (ie, those with urgency). FUNDING: National Institute for Health
      Research.

PMID- 26293317
TI  - Acute mesenteric ischemia: Utility of endovascular techniques.
AB  - INTRODUCTION: Acute mesenteric ischemia (AMI) has a high mortality. Early
      diagnosis and treatment are very important. In our institution there is a
      therapeutic protocol that includes endovascular techniques (ET) in patients with
      AMI without peritoneal irritation at diagnosis. The aim of this study was to
      evaluate the use of ET in conjunction with conventional surgery in the management
      of potentially reversible IMA diagnosed by computed tomography (CT-angiography).
      METHODS: Observational, descriptive and retrospective study that evaluated the
      use of ET in patients with AMI (arterial origin) in 2 periods (before and after
      the application of a protocol that includes ET), between 2009-2013. All patients
      were diagnosed by a CT-angiography, as the diagnostic technique of choice,
      because of the clinical and analytical suspicion. RESULTS: Our series included 73
      patients with IMA diagnosed by CT-angiography (45: 2009-2011; 28: 2012-2013).
      Leukocytosis was common (82%), high lactate levels are less frequent (47% vs.
      53%). There were 49 patients with IMA without peritoneal irritation. In 51% bowel
      resection surgery was performed (44% survival); 18%: revascularization by ET
      (survival 67%); 31%: palliative treatment (0% survival). 33% of patients
      undergoing first-line RVI needed a surgical rescue (bowel resection). The overall
      mortality was 67% (2009-2011) vs. 62% (2012-2013). CONCLUSIONS: Since the
      protocol application, there is a higher indication of ET in patients with AMI
      without peritoneal irritation, showing a decreased mortality. With ET
      application, there is a higher survival in these patients. In our experience, the
      use of ET in cases of AMI without peritoneal irritation at diagnosis, may
      increase survival.

PMID- 26293320
TI  - FDA issues warnings to duodenoscope makers linked to infection outbreaks.

PMID- 26293318
TI  - Firing-rate resonances in the peripheral auditory system of the cricket, Gryllus
      bimaculatus.
AB  - In many communication systems, information is encoded in the temporal pattern of
      signals. For rhythmic signals that carry information in specific frequency bands,
      a neuronal system may profit from tuning its inherent filtering properties
      towards a peak sensitivity in the respective frequency range. The cricket Gryllus
      bimaculatus evaluates acoustic communication signals of both conspecifics and
      predators. The song signals of conspecifics exhibit a characteristic pulse
      pattern that contains only a narrow range of modulation frequencies. We examined
      individual neurons (AN1, AN2, ON1) in the peripheral auditory system of the
      cricket for tuning towards specific modulation frequencies by assessing their
      firing-rate resonance. Acoustic stimuli with a swept-frequency envelope allowed
      an efficient characterization of the cells' modulation transfer functions. Some
      of the examined cells exhibited tuned band-pass properties. Using simple
      computational models, we demonstrate how different, cell-intrinsic or network
      based mechanisms such as subthreshold resonances, spike-triggered adaptation, as
      well as an interplay of excitation and inhibition can account for the
      experimentally observed firing-rate resonances. Therefore, basic neuronal
      mechanisms that share negative feedback as a common theme may contribute to
      selectivity in the peripheral auditory pathway of crickets that is designed
      towards mate recognition and predator avoidance. 

PMID- 26293319
TI  - Lentivirus-mediated shRNA interference of clusterin blocks proliferation,
      motility, invasion and cell cycle in the ovarian cancer cells.
AB  - BACKGROUND: In a previous analysis on the patients with ovarian cancers, we have
      found that clusterin is a biomarker associated with ovarian cancer in vivo and
      may be a prognostic factor associated with adverse outcome. Here, we explored the
      effect of lentivirus-mediated shRNA interference of clusterin, investigated
      whether clusterin was associated with adverse outcome of ovarian cancer cells in
      vitro. METHODS: OVCAR-3 and TOV-21G cell lines were infected with the lentivirus
      for delivering clusterin shRNA, and the stably transfected cells were selected.
      The effect of clusterin silencing was detected by western blotting assay. The
      proliferation, clonability, migration, invasion and cell cycle of two cell lines
      were detected separately by MTT assay, clone formation assay, scratch assay,
      transwell assay and fluorescence-activated cell sorting. RESULTS: Following
      clusterin silencing with shRNA, the expression of clusterin in two cell lines
      were decreased. And the proliferation, clonability, migration, invasion of these
      two cell lines were down-regulated apparently. The cell cycle of two cell lines
      was disturbed, cells in G1 phase was increased, but cells in G2 and S phase was
      decreased. CONCLUSIONS: The expression of clusterin is significantly correlated
      with the biological characteristics of ovarian cancer cells, it may be a
      potential molecular for ovarian cancer treatment.

PMID- 26293321
TI  - Retinol and Alpha-tocopherol in the Colostrum of Lactating Tunisian Women
      Delivering Prematurely: Associations with Maternal Characteristics.
AB  - BACKGROUND: This study aims to assess vitamin A and E concentrations in the
      premature colostrum of lactating Tunisian women and to identify maternal
      characteristics that may affect these concentrations. METHODS: Human colostrum
      was obtained from 105 mothers who gave birth prematurely in the Centre for
      Maternity and Neonatology of Tunis (Tunisia). Retinol and alpha-tocopherol were
      analyzed in the colostrum and in plasma by high-performance liquid
      chromatography. RESULTS: Retinol and alpha-tocopherol concentrations were 57.5 +/
      50.1 MUg/dL and 1222 +/- 772 MUg/dL in the colostrum, respectively, and 51.7 +/-
      20.0 MUg/dL and 1351 +/- 772 MUg/dL in plasma, respectively. Concentrations of
      each vitamin in the colostrum were positively correlated with their respective
      concentrations in plasma (r = 0.415, p = 0.001 for retinol and r = 0.392, p =
      0.003 for alpha-tocopherol). In multivariate analysis, colostrum vitamin A was
      associated with plasma vitamin A and preeclampsia, while colostrum vitamin E was
      associated with plasma vitamin E, gestational age, and preeclampsia. CONCLUSION:
      In Tunisian women, colostrum vitamin A and E levels are close to the average
      values reported in the literature. The levels are too low to cover the needs of
      very low birth weight (VLBW) infants, particularly in women with plasma vitamin
      deficiencies, preeclampsia, or very premature delivery. Given the undeniable
      beneficial effects of human colostrum, whenever feasible, VLBW infants should be
      fed colostrum. Infant vitamin A and E requirements should be met by milk
      fortification or supplementation.

PMID- 26293322
TI  - Risk factors for homicide victimization in post-genocide Rwanda: a population 
      based case- control study.
AB  - BACKGROUND: Homicide is one of the leading causes of mortality in the World.
      Homicide risk factors vary significantly between countries and regions. In
      Rwanda, data on homicide victimization is unreliable because no standardized
      surveillance system exists. This study was undertaken to identify the risk
      factors for homicide victimization in Rwanda with particular attention on the
      latent effects of the 1994 genocide. METHODS: A population-based matched case
      control study was conducted, with subjects enrolled prospectively from May 2011
      to May 2013. Cases of homicide victimization were identified via police reports,
      and crime details were provided by law enforcement agencies. Three controls were
      matched to each case by sex, 5-year age group and village of residence.
      Socioeconomic and personal background data, including genocide exposure, were
      provided via interview of a family member or through village administrators.
      Conditional logistic regression, stratified by gender status, was used to
      identify risk factors for homicide victimization. RESULTS: During the study
      period, 156 homicide victims were enrolled, of which 57 % were male and 43 % were
      female. The most common mechanisms of death were wounds inflicted by sharp
      instruments (knives or machetes; 41 %) followed by blunt force injuries (36.5 %).
      Final models indicated that risk of homicide victimhood increased with victim
      alcohol drinking patterns. There was a dose response noted for alcohol use: for
      minimal drinking versus none, adjusted odds ratio (aOR) = 3.1, 95%CI: 1,3-7.9;
      for moderate drinking versus none, aOR = 10.1, 95%CI: 3.7-24.9; and for heavy
      drinking versus none, aOR = 11.5, 95%CI: 3.6-36.8. Additionally, having no
      surviving parent (aOR = 2.7, 95%CI: 1.1-6.1), previous physical and/or sexual
      abuse (aOR = 28.1, 95%CI: 5.1-28.3) and drinking illicit brew and/or drug use
      (aOR = 7.7, 95%CI: 2.4-18.6) were associated with a higher risk of being killed.
      The test of interaction revealed that the variables that were significantly
      associated with a higher risk of homicide victimhood, did not exhibit any
      difference according to sex of the victim. However, the effect of belonging to a
      religion differed between women and men, but was significantly protective for
      both (aOR = 0.002, 95%CI: 0.001-0.054 and aOR = 0.20, 95%CI: 0.052-0.509,
      respectively). CONCLUSION: Homicide victims in Rwanda are relatively young and
      the proportion of female victims is one of the highest globally. Contrary to the
      initial study considerations, genocide exposure (either as a survivor or
      perpetrator) was not a significant predictor of homicide victimization. Rather,
      risk factors were similar to those described in other countries, regardless of
      gender status. Sensitizing communities against alcohol heavy drinking, and
      illicit brew drinking and/or drug abuse and physical or sexual violence could
      reduce the homicide rate in Rwanda.

PMID- 26293323
TI  - A low grade fibromyxoid sarcoma originating from the masseter muscle: a case
      report.
AB  - INTRODUCTION: Low grade fibromyxoid sarcoma is a distinctive variant of
      fibrosarcoma. We recently experienced a rare case of low grade fibromyxoid
      sarcoma arising in the masseter muscle. CASE PRESENTATION: A 63-year-old Korean
      woman with a large growing mass in her right parotid gland area for 1 year
      visited our clinic. Complete removal of the tumor was achieved by parotidectomy
      with facial nerve preservation. The tumor measured over 4cm with pathologic
      findings compatible with low grade fibromyxoid sarcoma. CONCLUSIONS: Low grade
      fibromyxoid sarcoma is an extremely rare tumor, and report of the present case is
      noteworthy since it represents a rare localization of low grade fibromyxoid
      sarcoma in the head and neck. Close follow up on a long-term basis is considered
      necessary because of its high potential to metastasize.

PMID- 26293324
TI  - "Everywhere but not specifically somewhere": a qualitative study on why the right
      to health is not explicit in the post-2015 negotiations.
AB  - BACKGROUND: The Millennium Development Goals expire at the end of 2015 and global
      negotiations are underway to finalise the post-2015 Sustainable Development
      Goals. Much activism has occurred encouraging a post-2015 health and development
      goal embedded in the highest attainable standard of health ('right to health').
      Despite this, the right to health was absent in three key post-2015
      intergovernmental Sustainable Development Goal proposals in 2014, one of which
      was reinforced by the United Nations General Assembly in September 2014 as the
      guiding document for ongoing interstate negotiations. This article examines why
      it appears the right to health, so far, is not gaining direct expression in post
      2015 discussion. METHODS: This qualitative research is part of a broader study
      using thematic and discourse analysis examining the high-level policy debate on
      health goals in the discourse of the formulation of the post-2015 Sustainable
      Development Goals. Key-informant interviews were conducted in two interview
      rounds in 2013 and 2014, with participants from multilateral and other
      organisations (government, academia, civil society and philanthropy) responsible
      for health in the post-2015 development agenda (or the post-2015 development
      agenda more broadly). This study synthesises data from both interview rounds on
      Health and Human Rights in post-2015 Sustainable Development Goal negotiations.
      RESULTS: Six reasons why the right to health may not have gained effective
      traction in the unfolding post-2015 Member State negotiations were found. The
      first three reasons relate to broader issues surrounding human rights' (including
      sexual and reproductive health and rights) positioning within international
      relations discourse, and the second three relate to the challenges of
      transforming the human right to health into a practically applied post-2015
      health goal. CONCLUSIONS: This paper reports the views of participants, many of
      who sit at the interface of United Nations and Member State negotiations, on the
      right to health's location (and projected trajectory) at two temporal junctions
      in evolving post-2015 negotiations. The interviews provide insight into high
      level hesitancy that the right to health be expressly incorporated in the final
      post-2015 health and development goal, as well as documents participants' doubt
      that rights language will explicitly frame the broader Sustainable Development
      Goals, their targets and indicators.

PMID- 26293325
TI  - When patients with epilepsy or "epilepsy" might need a pacemaker.

PMID- 26293326
TI  - Brain tumor clinical trials imaging: a (well-standardized) picture is worth a
      thousand words.

PMID- 26293327
TI  - Everolimus effectively blocks pulmonary metastases from meningioma.

PMID- 26293329
TI  - Diagnosis and Staging of Medication-Related Osteonecrosis of the Jaw.
AB  - The relationship between osteonecrosis of the jaw and bisphosphonate therapy was
      initially established more than 10 years ago. Since that time our understanding
      of this disease process has evolved as the direct result of clinical, basic
      science, and animal research initiatives. Medication-related osteonecrosis of the
      jaw (MRONJ) is a well-known entity now known to be associated with various
      antiresorptive therapies and recently with antiangiogenic medications. This
      article reviews the recently modified diagnostic criteria for MRONJ with a focus
      on the clinical, histopathologic, and imaging characteristics of this disease
      process.

PMID- 26293330
TI  - Pediatric Vascular Tumors of the Head and Neck.
AB  - Oral and maxillofacial surgeons are often involved in the diagnosis and treatment
      of vascular neoplasms of the head and neck. An incorrect diagnosis may lead to
      improper or unnecessary treatment. This article reviews the diagnosis and
      management of vascular tumors. 

PMID- 26293331
TI  - Preventive Strategies for Patients at Risk of Medication-related Osteonecrosis of
      the Jaw.
AB  - For patients at risk of osteonecrosis of the jaw (ONJ), information can be
      provided by the pharmaceutical manufacturer, pharmacist, prescribing physician,
      dentist, and oral and maxillofacial surgeon. Prevention strategies to reduce the
      incidence of osteonecrosis should be applied as soon as it is determined that a
      patient will be placed on antiresorptive medication. Proper screening involves a
      comprehensive oral examination with radiographs followed by oral hygiene
      instruction and necessary dental treatment; surgical techniques and adjunctive
      therapies that favor optimum healing of bone and soft tissue decrease the risk of
      ONJ. No dental procedures are absolutely contraindicated. 

PMID- 26293332
TI  - Conditions for sustainability of Academic Collaborative Centres for Public Health
      in the Netherlands: a mixed methods design.
AB  - BACKGROUND: Contemporary research should increasingly be carried out in the
      context of application. Nowotny called this new form of knowledge production Mode
      2. In line with Mode-2 knowledge production, the Dutch government in 2006
      initiated the so-called Academic Collaborative Centres (ACC) for Public Health.
      The aim of these ACCs is to build a regional, sustainable knowledge-sharing
      network to deliver socially robust knowledge. The present study aims to highlight
      the enabling and constraining push and pull factors of these ACCs in order to
      assess whether the ACCs are able to build and strengthen a sustainable integrated
      organizational network between public health policy, practice, and research.
      METHODS: Our empirical analysis builds on a mixed methods design. Quantitative
      data was derived from records of a survey sent to all 11 ACCs about personnel
      investments, number and nature of projects, and earning power. Qualitative data
      was derived from 21 in-depth interviews with stakeholders involved. The
      interviews were tape-recorded, transcribed, and manually coded as favourable or
      unfavourable pull or push factors. RESULTS: The extra funding appeared to be the
      most enabling push factor. The networks secured external grants for about 150
      short- and long-term Mode-2 knowledge production projects in the past years.
      Enabling pull factors improved, especially the number of policy-driven short-term
      research projects. Exchange agents were able to constructively deal with the
      constraining push factors, like university's publication pressure and budget
      limitations. However, the constraining pull factors like local government's
      involvement and their low demand for scientific evidence were difficult to
      overcome. CONCLUSIONS: A clear improvement of the organizational networks was
      noticed whereby the ACC's were pushed rather than pulled. Efforts are needed to
      increase the demand for scientific and socially robust evidence from policymakers
      and to resolve the regime differences between the research and policy systems, in
      order to make the bidirectionality of the links sustainable.

PMID- 26293334
TI  - A combinatorial systematic evolution of ligands by exponential enrichment method
      for selection of aptamer against protein targets.
AB  - Aptamers are synthetic DNA recognition elements which form unique conformations
      that enable them to bind specifically to their targets. In the present study, an
      attempt was made to standardize a new modified combinatorial method comprising of
      Ni-NTA affinity Systematic Evolution of Ligands by Exponential Enrichment (SELEX;
      based on affinity between His tag protein and Ni-NTA), membrane SELEX (based on
      immobilization of protein on nitrocellulose membrane), and microtiter plate based
      SELEX (to monitor affinity and to enrich the selected aptamers) for protein
      targets. For experimental evaluation, staphylococcal interotoxin B was the
      molecule chosen. The new combinatorial method enhanced selection ability up to
      51.20 % in comparison with individual conventional procedures. Employing this
      method following six rounds of selection, high-affinity aptamers with very
      different properties could be obtained with a dissociation constant (K d) value
      as low as 34.72 +/- 25.09 nM. The optimal aptamers could be employed in
      fluorescence binding assay, enzyme-linked oligonucleotide assays, and aptamer
      based Western blot assay for characterization and detection. These results pave a
      potential path without using of any robotics for high-throughput generation of
      aptamers with advantages in terms of rapidity, simplicity, and ease in handling.

PMID- 26293333
TI  - Human collagen XV is a prominent histopathological component of sinusoidal
      capillarization in hepatocellular carcinogenesis.
AB  - BACKGROUND: Increased expression of collagen XV has been reported in
      hepatocellular carcinogenesis in mice. The aim of this study was to confirm the
      previous murine findings in human hepatocellular carcinoma (HCC) specimens, along
      with the histopathological distribution of collagen XV in tumoral tissues.
      METHODS: Sixty-three primary HCC specimens were examined. Immunostaining of
      collagen XV and quantitative reverse transcriptional PCR of COL15A1, which
      encodes collagen XV, were performed. RESULTS: Positive staining of collagen XV
      was observed in all tumoral regions, regardless of differentiation level or
      pathological type of HCC, along the sinusoid-like endothelium, whereas collagen
      XV was not expressed in any non-tumoral region. The intensity score of collagen
      XV immunostaining and the mRNA value of COL15A1 were significantly correlated.
      COL15A1 expression in tumors was 3.24-fold higher than in non-tumoral regions.
      Multivariate analysis showed that COL15A1 expression was significantly higher in
      the absence of hepatitis virus and moderately differentiated HCC. CONCLUSIONS:
      COL15A1 mRNA was up-regulated in HCC and collagen XV was expressed along the
      sinusoid-like endothelium of HCC but not in non-tumoral regions, which implies
      that collagen XV contributes to the capillarization of HCC.

PMID- 26293335
TI  - Characteristics of a novel thermophilic heterotrophic bacterium, Anoxybacillus
      contaminans HA, for nitrification-aerobic denitrification.
AB  - A strain bacterium that is thermophilic, heterotrophic nitrifying, and aerobic
      denitrifying was isolated and identified as Anoxybacillus contaminans HA for the
      first time. The identification was based on morphological and physiological
      characterizations, together with phylogenetic analysis of 16S rDNA sequence. The
      strain possessed excellent tolerance to high temperatures, with 55  degrees C as
      its optimum and 60  degrees C as viable. Moreover, NH4 (+)-N and NO3 (-)-N could
      be efficiently removed under thermophilic and solely aerobic conditions, with
      little intermediate accumulation. Average removal efficiencies of NH4 (+)-N and
      NO3 (-)-N at 55  degrees C reached 71.0 and 74.7 %, respectively, with removal
      rates of 5.83 and 32.08 mg l(-1) h(-1), respectively. Single-factor experiments
      suggested that the optimal conditions for both heterotrophic nitrification and
      aerobic denitrification were glucose as carbon source, NH4 (+)-N range of 50-200
      mg l(-1), and wide NO3 (-)-N range of 200-1000 mg l(-1). These results indicated
      that strain HA had heterotrophic nitrification and aerobic denitrification
      abilities, as well as the notable ability to remove ammonium under thermophilic
      condition. Thus, this strain has potential application in waste-gas treatment. 

PMID- 26293336
TI  - Enzymatic technologies for remediation of hydrophobic organic pollutants in soil.
AB  - Worldwide there are numerous contaminated sites as a result of the widespread
      production and use of chemicals in industrial and military activities as well as
      poor schemes of waste disposal and accidental spillages. The implementation of
      strategies for decontamination and restoration of polluted sites has become a
      priority, being bioremediation with biological agents a promising alternative.
      Enzyme-based technologies offer several advantages over the use of microbial
      cells, provided that the biocatalyst meets specific requirements: efficiency to
      remove the target pollutant/s, non-dependency on expensive coenzymes or
      cofactors, enzyme stability, and an affordable production system. In this mini
      review, the direct application of enzymes for in situ soil bioremediation is
      explored, and also novel ex situ enzymatic technologies are presented. This new
      perspective provides a valuable insight into the different enzymatic alternatives
      for decontamination of soils. Examples of recent applications are reported,
      including pilot-scale treatments and patented technologies, and the principles of
      operation and the main requirements associated are described. Furthermore, the
      main challenges regarding the applicability of enzymatic technologies for
      remediation of hydrophobic organic pollutants from soil are discussed. 

PMID- 26293337
TI  - Hydrolysis of by-product adenosine diphosphate from 3'-phosphoadenosine-5'
      phosphosulfate preparation using Nudix hydrolase NudJ.
AB  - 3'-Phosphoadenosine-5'-phosphosulfate (PAPS) is the obligate cosubstrate and
      source of the sulfonate group in the chemoenzymatic synthesis of heparin, a
      clinically used anticoagulant drug. Previously, we have developed a method to
      synthesize PAPS with Escherichia coli crude extracts, which include three
      overexpressed enzymes and a fourth unidentified protein. The unknown protein
      degrades adenosine diphosphate (ADP), the by-product of PAPS synthesis reaction.
      To further understand and control the process of in vitro enzymatic PAPS
      synthesis, we decide to identify the fourth protein and develop a defined method
      to synthesize PAPS using purified enzymes. Here, we show that the purified Nudix
      hydrolase NudJ degrades ADP at high efficiency and serves as the fourth enzyme in
      PAPS synthesis. Under the defined condition of PAPS synthesis, all of the 10-mM
      ADP is hydrolyzed to form adenosine monophosphate (AMP) in a 15-min reaction. ADP
      is a better substrate for NudJ than adenosine triphosphate (ATP). Most
      importantly, the purified NudJ does not cleave the product PAPS. The removal of
      ADP makes the PAPS peak more separable from other components in the
      chromatographic purification process. This developed enzymatic approach of PAPS
      production will contribute to the chemoenzymatic synthesis of heparin. 

PMID- 26293338
TI  - Diversity of phosphorylases in glycoside hydrolase families.
AB  - Phosphorylases are useful catalysts for the practical preparation of various
      sugars. The number of known specificities was 13 in 2002 and is now 30. The
      drastic increase in available genome sequences has facilitated the discovery of
      novel activities. Most of these novel phosphorylase activities have been
      identified through the investigations of glycoside hydrolase families containing
      known phosphorylases. Here, the diversity of phosphorylases in each family is
      described in detail. 

PMID- 26293339
TI  - Erratum to: Development and performance assessment of a qualitative SYBR(r) green
      real-time PCR assay for the detection of Aspergillus versicolor in indoor air.

PMID- 26293340
TI  - The other side of epilepsy.

PMID- 26293341
TI  - A novel cell-printing method and its application to hepatogenic differentiation
      of human adipose stem cell-embedded mesh structures.
AB  - We report a cell-dispensing technique, using a core-shell nozzle and an absorbent
      dispensing stage to form cell-embedded struts. In the shell of the nozzle, a
      cross-linking agent flowed continuously onto the surface of the dispensed bioink
      in the core nozzle, so that the bioink struts were rapidly gelled, and any
      remnant cross-linking solution during the process was rapidly absorbed into the
      working stage, resulting in high cell-viability in the bioink strut and stable
      formation of a three-dimensional mesh structure. The cell-printing conditions
      were optimized by manipulating the process conditions to obtain high mechanical
      stability and high cell viability. The cell density was 1 * 10(7) mL(-1), which
      was achieved using a 3-wt% solution of alginate in phosphate-buffered saline, a
      mass fraction of 1.2 wt% of CaCl2 flowing in the shell nozzle with a fixed flow
      rate of 0.08 mL min(-1), and a translation velocity of the printing nozzle of 10
      mm s(-1). To demonstrate the applicability of the technique, preosteoblasts and
      human adipose stem cells (hASCs) were used to obtain cell-laden structures with
      multi-layer porous mesh structures. The fabricated cell-laden mesh structures
      exhibited reasonable initial cell viabilities for preosteoblasts (93%) and hASCs
      (92%), and hepatogenic differentiation of hASC was successfully achieved. 

PMID- 26293342
TI  - Magnetic octadecyl-based matrix solid-phase dispersion coupled with gas
      chromatography with mass spectrometry in a proof-of-concept determination of
      multi-class pesticide residues in carrots.
AB  - A novel procedure is put forward based on the combination of the well-established
      matrix solid-phase dispersion and the magnetic and sorption properties of
      magnetic octadecyl in the presence of n-octanol and was employed in a proof-of
      concept sample preparation and determination of several classes of pesticide
      residues in carrots. The procedure does not require the transfer of blend to
      cartridge and subsequent packing, nor any co-sorbent for extract clean up. The
      hydrophobic magnetic nanoparticles utilized as a sorbent, can be retrieved by n
      octanol under the application of a magnetic field due to hydrophobic
      interactions. Elution of pesticide residues is then carried out with an organic
      solvent. A total of 26 pesticides were included in this procedure and the target
      compounds were analyzed using gas chromatography with mass spectrometry in the
      selective ion monitoring mode. The average extraction recoveries obtained from
      carrot samples fortified at three different concentrations (20, 50, and 500
      MUg/kg) were 77-107%. The estimated limits of quantitation for most target
      analytes were in the low MUg/kg level. The study demonstrates that the proposed
      extraction procedure is simple and effective, avoiding a clean-up step for the
      sample preparation of vegetable. 

PMID- 26293343
TI  - Rnaset2 inhibits melanocyte outgrowth possibly through interacting with shootin1.
AB  - BACKGROUND: Impaired dendrite outgrowth of melanocytes is one of the reasons
      triggering vitiligo. RNASET2 was identified as one of the risk genes for vitiligo
      in a GWAS study conducted in the Chinese Han population. However, the role of
      Rnaset2 in the outgrowth of melanocytes is rarely studied. OBJECTIVE: This study
      is to investigate the effects of Rnaset2 in regulating the outgrowth of
      melanocytes and its interacting proteins. METHODS: Stress conditions (UV
      irradiation, hydrogen peroxide, and lipopolysaccharides) were applied to primary
      human epidermal melanocytes (HEMs) and epidermal keratinocytes (HEKs). HEKs with
      Rnaset2 overexpression were co-cultured with HEMs. Rnaset2 expression levels were
      detected by ELISA. HEMs, HEKs and A375 cells were treated with recombinant
      Rnaset2 protein and actin network was observed with fluorescence microscope. Cell
      migration assay was performed using nuclepore filters after incubating A375 cells
      with recombinant Rnaset2 protein. Human proteome microarray was performed to
      identify proteins interacting with Rnaset2. Co-immunoprecipitation was conducted
      to verify the results. RESULTS: Our results showed that after exposing to stress
      conditions, Rnaset2 expression and secretion by HEKs and HEMs were increased. Co
      culture of HEKs and HEMs showed that outgrowth of HEMs was inhibited by Rnaset2
      overexpression in HEKs. Additionally, human recombinant Rnaset2 protein treatment
      altered the actin network of HEMs, HEKs and A375 cells. The migration of A375
      cells was also inhibited by human recombinant Rnaset2 protein treatment. Human
      proteome microarray identified shootin1, an important protein involved in axon
      outgrowth, as one of the interacting proteins of Rnaset2. Co-immunoprecipitation
      confirmed that Rnaset2 interacted with shootin1 in vitro. CONCLUSION: Rnaset2
      inhibits melanocyte outgrowth through interacting with shootin1 and this effect
      may be associated with vitiligo pathogenesis. Rnaset2 may be a potential
      therapeutic target for vitiligo.

PMID- 26293344
TI  - Gold Nanomaterials at Work in Biomedicine.

PMID- 26293345
TI  - Evaluation of the diagnostic accuracy of nonstructural protein 1 Ag-based tests
      for dengue virus in Asian population: a meta-analysis.
AB  - BACKGROUND: Nonstructural protein 1 (NS1) Ag-based tests are useful for detecting
      dengue virus (DENV), but there is lack of evidence on the diagnostic accuracy of
      NS1 Ag-based tests in Asian population. Thus, we conducted this meta-analysis to
      obtain the overall estimated and summarized performance of the NS1 Ag-based tests
      in the detection of DENV in Asia. METHODS: PubMed, Embase and Medline were
      searched for studies that evaluated the diagnostic validity of NS1 Ag-based tests
      between January 1990 and November 2014. Data were analyzed by Meta-Disc and STATA
      software. RESULTS: A total of 18 studies including 3342 dengue cases and 1904
      control cases which fulfilled the inclusion criteria were considered for
      analysis. The pooled sensitivity and specificity for NS1 Ag-based tests was 66 %
      (95 % CI 64.5-67.5) and 97.9 % (95 % CI 97.3-100), respectively. STRIP has the
      overall highest sensitivity (72.9 %, 95 % CI 70.1-75.5). According to viral
      serotype, the test with the highest sensitivity for DENV1, DENV2 and DENV3 were
      Platelia (83.7 %, 95 % CI 79.7-87.1), Panbio (71.8 %, 95 % CI 65.5-80.9) and
      STRIP (81.9 %, 95 % CI 75.5-87.2) respectively. The highest sensitivity for
      primary infection was Platelia (95.1 %, 95 % CI 92.6-96.9) and for secondary
      infection was STRIP (64 %, 95 % CI 53.2-73.9). CONCLUSION: Our meta-analysis
      suggests that NS1 Ag-based test is a good diagnostic method for DENV with a high
      specificity. However, viral serotype, serological status, clinical severity and
      the duration of illness are the main factors influencing the diagnostic accuracy.

PMID- 26293346
TI  - Sacrificial adhesive bonding: a powerful method for fabrication of glass
      microchips.
AB  - A new protocol for fabrication of glass microchips is addressed in this research
      paper. Initially, the method involves the use of an uncured SU-8 intermediate to
      seal two glass slides irreversibly as in conventional adhesive bonding-based
      approaches. Subsequently, an additional step removes the adhesive layer from the
      channels. This step relies on a selective development to remove the SU-8 only
      inside the microchannel, generating glass-like surface properties as demonstrated
      by specific tests. Named sacrificial adhesive layer (SAB), the protocol meets the
      requirements of an ideal microfabrication technique such as throughput,
      relatively low cost, feasibility for ultra large-scale integration (ULSI), and
      high adhesion strength, supporting pressures on the order of 5 MPa. Furthermore,
      SAB eliminates the use of high temperature, pressure, or potential, enabling the
      deposition of thin films for electrical or electrochemical experiments. Finally,
      the SAB protocol is an improvement on SU-8-based bondings described in the
      literature. Aspects such as substrate/resist adherence, formation of bubbles, and
      thermal stress were effectively solved by using simple and inexpensive
      alternatives. 

PMID- 26293347
TI  - Replication dynamics in fission and budding yeasts through DNA polymerase
      tracking.
AB  - The dynamics of eukaryotic DNA polymerases has been difficult to establish
      because of the difficulty of tracking them along the chromosomes during DNA
      replication. Recent work has addressed this problem in the yeasts
      Schizosaccharomyces pombe and Saccharomyces cerevisiae through the engineering of
      replicative polymerases to render them prone to incorporating ribonucleotides at
      high rates. Their use as tracers of the passage of each polymerase has provided a
      picture of unprecedented resolution of the organization of replicons and
      replication origins in the two yeasts and has uncovered important differences
      between them. Additional studies have found an overlapping distribution of DNA
      polymorphisms and the junctions of Okazaki fragments along mononucleosomal DNA.
      This sequence instability is caused by the premature release of polymerase delta
      and the retention of non proof-read DNA tracts replicated by polymerase alpha.
      The possible implementation of these new experimental approaches in multicellular
      organisms opens the door to the analysis of replication dynamics under a broad
      range of genetic backgrounds and physiological or pathological conditions.

PMID- 26293348
TI  - Cellular deficiency in the RGS10 protein facilitates chemoresistant ovarian
      cancer.
AB  - More than 30 regulators of G protein signaling (RGS) proteins encompass the RGS
      protein superfamily of critical regulators essential to cellular homeostasis.
      There is enormous structural and functional diversity among the RGS superfamily,
      and as such they serve a wide range of functions in regulating cell biology and
      physiology. Recent evidence has suggested roles for multiple RGS proteins in
      cancer initiation and progression, which has prompted research toward the
      potential modulation of these proteins as a new approach in cancer therapy. This
      article will discuss basic RGS molecular pharmacology, summarize the cellular
      functions and epigenetic regulation of RGS10, review ovarian cancer chemotherapy
      and describe the role of RGS10 in ovarian cancer survival signaling. 

PMID- 26293349
TI  - Non-quantitative adjustment of offspring sex ratios in pollinating fig wasps.
AB  - Fig wasp is one of the most well known model systems in examining whether or not
      the parents could adjust their offspring sex ratio to maximize their gene
      frequency transmission in next generations. Our manipulative experiments showed
      that, in all of the five pollinator wasps of figs (Agaonidae) that have different
      averages of foundress numbers per syconium, almost the same proportions of male
      offspring are produced in the experiment that foundresses deposit one hour then
      are killed with ether (66.1%-70.1%) and over the lifespan of each foundress
      (14.0%-21.0%). The foundresses tend to deposit their male eggs prior to female
      eggs. The observed increase in the proportion of male offspring as a function of
      foundress number results from density-dependent interference competition among
      the foundresses. These results showed that the selection of gene frequency
      transmission through the behavioral adjustment in the evolution of sex ratio does
      not exist in these five fig wasps. The results here implied that genetic
      adjustment mechanisms of the sex ratio of fig wasps can only be triggered to be
      on or off and that the foundresses can not quantitatively adjust their sex ratio
      according to increased environmental selection pressure. 

PMID- 26293350
TI  - Synthesis of BiOI@(BiO)2CO3 facet coupling heterostructures toward efficient
      visible-light photocatalytic properties.
AB  - In this paper, BiOI@(BiO)2CO3 facet coupling heterostructures were synthesized
      via exfoliation and ion exchange, and characterized by X-ray diffraction (XRD)
      patterns, scanning electron microscopy (SEM), high-resolution transmission
      electron microscopy (HRTEM), UV-vis diffuse reflectance spectra (DRS), X-ray
      photoelectron spectroscopy (XPS), photoluminescence (PL) spectra and valence-band
      XPS spectra. With the reaction time increasing, more BiOI can be transformed to
      (BiO)2CO3, and BiOI@(BiO)2CO3 facet coupling heterostructures were obtained. The
      photocatalytic results showed that BiOI@(BiO)2CO3 displays much higher
      photocatalytic activity than BiOI and (BiO)2CO3 under visible-light. The
      photocatalytic mechanism study revealed that BiOI@(BiO)2CO3 has strong adsorption
      for RhB molecules due to the ultrathin nanosheets and higher BET, and displays
      better separation efficiency of photoinduced charge carriers and higher
      photocurrent due to the {001}/{001} facet coupling. 

PMID- 26293351
TI  - The Psychosocial and Independent Living Donor Advocate Evaluation and Post
      surgery Care of Living Donors.
AB  - Solid organ transplantation as a treatment for end stage organ failure has been
      an accepted treatment option for decades. Despite advances in medicine and
      technology, and increased awareness of organ donation and transplantation, the
      gap between supply and demand continues to widen. Living donation has been an
      option that has increased the number of transplants despite the continued
      shortage of deceased organs. In the early 2000s live donor transplantation
      reached an all-time high in the United States. As a result, a consensus meeting
      was convened in 2000 to increase the oversight of living donor transplantation.
      Both the Centers for Medicare and Medicaid Services and the United Network for
      Organ Sharing developed regulations that transplant programs performing live
      donor transplantation. These regulations and guidelines involve the education,
      evaluation, informed consent process and living donor follow-up care. Two areas
      in which had significant changes included the psychosocial and the independent
      living donor advocate (ILDA) evaluation. The purpose of this paper was to outline
      the current regulations and guidelines associated with the psychosocial and ILDA
      evaluation as well as provide further recommendations for the administration of a
      high quality evaluation of living donors. The goals and timing of the evaluation
      and education of donors; qualifications of the health care providers performing
      the evaluation; components of the evaluation; education provided to donors;
      documentation of the evaluation; participation in the selection committee
      meeting; post-decline and post-donation care of donors is described. Caveats
      including the paired donor exchange programs and non-directed and directed
      donation are also considered. 

PMID- 26293352
TI  - Modern treatment in Parkinson's disease, a personal approach.
AB  - There are many guidelines available concerning the treatment of Parkinson's
      disease. Most of these advocate treating young-onset patients with a dopamine
      agonist and older patients with levodopa. The rationale behind this
      recommendation has its origins in the side effects associated with each of these
      drug classes: whilst levodopa leads to dyskinesia, which may not be relevant for
      patients with a limited life-expectancy, dopamine agonists have a much longer
      plasma half life which probably leads to more continuous dopamine receptor
      stimulation and thus decreases the occurrence and severity of dyskinesia.
      However, the side effects associated with the use of dopamine agonists, such as
      sleepiness, orthostatic problems, hallucinations and impulse control disorders
      are a drawback. In this overview, the hypothesis will be put forward that perhaps
      such a strict distinction is no longer needed. A new idea may be the early
      combination of levodopa with a dopamine agonist which would provide good clinical
      efficacy and, because of the relatively low doses involved, would reduce the side
      effects associated with both substances. MAO-B inhibitors may be a good option
      for early treatment and especially for patients who experience first motor
      fluctuations. Similarly, and particularly if a wearing-off symptom is present,
      COMT inhibitors smoothen and prolong the action of levodopa. More invasive
      escalation therapy comes into play when patients reach the advanced stages with
      problems of insufficient motor control, such as bradykinesia, rigidity and
      resting tremor, combined with on-time dyskinesia. The use of all oral and
      invasive treatment has to be individualized to gain a good motor and non-motor
      control and especially a good quality of life. 

PMID- 26293353
TI  - Deciphering common and specific transcriptional immune responses in pea towards
      the oomycete pathogens Aphanomyces euteiches and Phytophthora pisi.
AB  - BACKGROUND: Root rot caused by Aphanomyces euteiches is one of the most
      destructive pea diseases while a distantly related species P. pisi has been
      recently described as the agent of pea and faba bean root rot. These two oomycete
      pathogens with different pathogenicity factor repertories have both evolved
      specific mechanisms to infect pea. However, little is known about the genes and
      mechanisms of defence against these pathogens in pea. In the present study, the
      transcriptomic response of pea to these two pathogens was investigated at two
      time points during early phase of infection using a Medicago truncatula
      microarray. RESULTS: Of the 37,976 genes analysed, 574 and 817 were
      differentially expressed in response to A. euteiches at 6 hpi and 20 hpi,
      respectively, while 544 and 611 genes were differentially regulated against P.
      pisi at 6 hpi and 20 hpi, respectively. Differentially expressed genes associated
      with plant immunity responses were involved in cell wall reinforcement, hormonal
      signalling and phenylpropanoid metabolism. Activation of cell wall modification,
      regulation of jasmonic acid biosynthesis and induction of ethylene signalling
      pathway were among the common transcriptional responses to both of these
      oomycetes. However, induction of chalcone synthesis and the auxin pathway were
      specific transcriptional changes against A. euteiches. CONCLUSIONS: Our results
      demonstrate a global view of differentially expressed pea genes during compatible
      interactions with P. pisi and A. euteiches at an early phase of infection. The
      results suggest that distinct signalling pathways are triggered in pea by these
      two pathogens that lead to common and specific immune mechanisms in response to
      these two oomycetes. The generated knowledge may eventually be used in breeding
      pea varieties with resistance against root rot disease.

PMID- 26293355
TI  - Catalyst Control of Selectivity in CO2 Reduction Using a Tunable Heterobimetallic
      Effect.
AB  - A tunable bimetallic effect on product selectivity in catalytic CO2 reduction was
      identified using N-heterocyclic carbene-ligated Cu complexes. While the
      monometallic Cu-only system catalyzes hydroboration of CO2 with pinacolborane to
      produce formate exclusively, introducing a bimetallic effect with analogous Cu
      Fe, Cu-W, and Cu-Mo catalysts produces mixtures of formate and CO. Within a
      series of isosteric catalysts, the selectivity of CO versus formate was
      controlled by tuning the electronic nature of the Cu/M pairing, with high
      selectivity for CO being achieved using a Cu-Mo catalyst. 

PMID- 26293354
TI  - Genetic structure of the Kuwaiti population revealed by paternal lineages.
AB  - OBJECTIVE: We analyzed the Y-chromosome haplogroup diversity in the Kuwaiti
      population to gain a more complete overview of its genetic landscape. METHOD: A
      sample of 117 males from the Kuwaiti population was studied through the analysis
      of 22 Y-SNPs. The results were then interpreted in conjunction with those of
      other populations from the Middle East, South Asia, North and East Africa, and
      East Europe. RESULTS: The analyzed markers allowed the discrimination of 19
      different haplogroups with a diversity of 0.7713. J-M304 was the most frequent
      haplogroup in the Kuwaiti population (55.5%) followed by E-M96 (18%). They
      revealed a genetic homogeneity between the Kuwaiti population and those of the
      Middle East (FST  = 6.1%, P-value < 0.0001), although a significant correlation
      between genetic and geographic distances was found (r = 0.41, P-value = 0.009).
      Moreover, the nonsignificant pairwise FST genetic distances between the Kuwait
      population on the one hand and the Arabs of Iran and those of Sudan on the other,
      corroborate the hypothesis of bidirectional gene flow between Arabia and both
      Iran and Sudan. CONCLUSION: Overall, we have revealed that the Kuwaiti population
      has experienced significant gene flow from neighboring populations like Saudi
      Arabia, Iran, and East Africa. Therefore, we have confirmed that the population
      of Kuwait is genetically coextensive with those of the Middle East.

PMID- 26293356
TI  - Receptors, G proteins, and integration of calcium signalling.

PMID- 26293357
TI  - Thermal stability and conformation of antiparallel duplexes formed by P
      stereodefined phosphorothioate DNA/LNA chimeric oligomers with DNA and RNA
      matrices.
AB  - 3'-O-(2-Thio-4,4-pentamethylene-1,3,2-oxathiaphospholane) derivatives of LNA-type
      nucleosides (LNA-OTPs, 2a-d; B' = Thy, Ade(Bz), Cyt(Bz), Gua(dmf), respectively)
      were synthesized and separated into pure P-diastereomers. X-ray analysis allowed
      for assignment of the absolute configuration of the phosphorus atom in the
      detritylated, fast-eluting diastereomer 2a. The diastereomerically pure LNA-OTP
      monomers were used in solid phase synthesis of P-stereodefined chimeric PS
      (DNA/LNA) 11-mers containing 2-3 LNA units. Formally, among the phosphorothioate
      oligomers the biggest enhancement in thermal stability of Watson-Crick paired
      duplexes was found for [SP-PS]-(DNA/LNA)/RNA duplexes (on average 8.2  degrees C
      per LNA nucleotide), followed by [RP-PS]-(DNA/LNA)/RNA (6.3  degrees C), [RP-PS]
      (DNA/LNA)/DNA (3.8  degrees C) and [SP-PS]-(DNA/LNA)/DNA (2.4  degrees C per LNA
      nucleotide). However, detailed analysis of the thermal dissociation data showed
      that the thermal stability of (PS-LNA)-containing duplexes does not depend on the
      spatial orientation of the sulfur atoms. This conclusion received support from CD
      measurements.

PMID- 26293359
TI  - Positron emission tomography: An additional prognostic tool in dilated
      cardiomyopathy?

PMID- 26293358
TI  - Prognostic value of heart rate response during regadenoson stress myocardial
      perfusion imaging in patients with end stage renal disease.
AB  - BACKGROUND: Blunted heart rate response (HRR) to vasodilator stress agents is
      associated with worse outcomes. There are limited data assessing the effect of
      impaired HRR to regadenoson among patients with end-stage renal disease (ESRD)
      undergoing stress myocardial perfusion imaging (MPI). METHODS: We prospectively
      followed patients with ESRD enrolled in the ASSUAGE and ASSUAGE-CKD trials. HRR
      was defined as 100*(peak stress heart rate-resting heart rate)/resting heart
      rate. Study cohort was dichotomized to blunted and normal HRR groups according to
      an established median HRR value <28% or >=28%, which were propensity-score
      matched based on 22 clinical and imaging covariates. The Primary endpoint was all
      cause death. The secondary cardiac-specific endpoints included: (1) the composite
      endpoint of cardiac death or myocardial infarction; (2) the composite endpoint of
      cardiac death, myocardial infarction, or late (>90 days) coronary
      revascularization. RESULTS: There were 303 patients followed for 35 +/- 10
      months. In the entire cohort, there was a stepwise increase in the rates of death
      and all secondary endpoints with worsening HRR (P values <=.001). Blunted HRR
      (<28%) was associated with increased risk of death (unadjusted hazard ratio 4.10
      [1.98-8.46], P < .001) and all secondary endpoints (P <= .001). After
      multivariate adjustment, HRR remained an independent predictor of mortality and
      secondary endpoints whether used as continuous or dichotomous variable, and added
      incremental prognostic value for all-cause death (P = .046). Blunted HRR was
      associated with increased event rate among patients with normal myocardial
      perfusion (P = .001) and abnormal perfusion (P = .053). In the propensity-matched
      cohort of 132 patients (66 in each group), blunted HRR was associated with
      significant increase in all-cause death (21% vs. 5%, HR 5.09 [1.46-17.7],
      P=.011), and similarly for the secondary endpoints. CONCLUSION: Blunted HRR
      (<28%) to regadenoson is a strong and independent predictor of death and
      cardiovascular events in patients with ESRD and adds incremental prognostic
      value.

PMID- 26293360
TI  - Expanding the Horizons of Nuclear Cardiology: Disease Management.

PMID- 26293361
TI  - Prevention of enamel demineralization with a novel fluoride strip: enamel surface
      composition and depth profile.
AB  - There is no topically applicable low concentration fluoride delivery device
      available for caries prevention. This study was aimed to assess the use of a low
      concentration (1450 ppm) fluoride strip as an effective fluoride delivery system
      against enamel demineralization. The enamel surface composition and calcium
      deficient hydroxyapatite or toothpaste treatments were investigated using X-ray
      photoelectron spectroscopy. In vitro enamel demineralization was assayed using a
      pH cycling model and the dissolution of calcium ions from the treated specimens
      was quantified using ion chromatography. After 24-hr fluoride-strip treatment,
      the enamel was covered with a CaF2 layer which showed a granular morphology of 1
      MUm in size. Below the CaF2 layer was a region of mixed fluorapatite and CaF2.
      Fluoride infiltrated extensively in enamel to produce highly fluorinated
      fluorohydroxyapatite. In comparison, low-fluoride-level fluorinated
      fluorohydroxyapatite was formed on the enamel specimen exposed to toothpaste. The
      treatments with the fluoride strip as short as 1 hr significantly inhibited
      enamel demineralization. The fluoride strip was effective for topical fluoride
      delivery and inhibited in vitro demineralization of enamel by forming CaF2 and
      fluoride-containing apatites at the enamel surface. It exhibited the potential as
      an effective fluoride delivery device for general use in prevention of caries. 

PMID- 26293363
TI  - Office Bearers of the Australian and New Zealand Society of Nephrology.

PMID- 26293364
TI  - 2015 Keynote Speakers.

PMID- 26293366
TI  - 2015 Seminar Speakers.

PMID- 26293365
TI  - 2015 ANZSN Society Sponsors.

PMID- 26293362
TI  - Advanced MRI for carotid plaque imaging.
AB  - Atherosclerosis is the ubiquitous underling pathological process that manifests
      in heart attack and stroke, cumulating in the death of one in three North
      American adults. High-resolution magnetic resonance imaging (MRI) is able to
      delineate atherosclerotic plaque components and total plaque burden within the
      carotid arteries. Using dedicated hardware, high resolution images can be
      obtained. Combining pre- and post-contrast T1, T2, proton-density, and
      magnetization-prepared rapid acquisition gradient echo weighted fat-saturation
      imaging, plaque components can be defined. Post-processing software allows for
      semi- and fully automated quantitative analysis. Imaging correlation with
      surgical specimens suggests that this technique accurately differentiates plaque
      features. Total plaque burden and specific plaque components such as a thin
      fibrous cap, large fatty or necrotic core and intraplaque hemorrhage are accepted
      markers of neuroischemic events. Given the systemic nature of atherosclerosis,
      emerging science suggests that the presence of carotid plaque is also an
      indicator of coronary artery plaque burden, although the preliminary data
      primarily involves patients with stable coronary disease. While the availability
      and cost-effectiveness of MRI will ultimately be important determinants of
      whether carotid MRI is adopted clinically in cardiovascular risk assessment, the
      high accuracy and reliability of this technique suggests that it has potential as
      an imaging biomarker of future risk. 

PMID- 26293368
TI  - ANZSN Program at a Glance.

PMID- 26293367
TI  - 2015 Abstract Reviewers.

PMID- 26293370
TI  - ANZSN ASM Detailed Program.

PMID- 26293369
TI  - Additional Meetings at a Glance.

PMID- 26293371
TI  - Nephrology and Transplantation Update Course.

PMID- 26293372
TI  - Renal Dietitians Day Workshop.

PMID- 26293373
TI  - ANZSN Renal Scientists Workshop.

PMID- 26293375
TI  - 51st Annual Scientific Meeting of the Australian and New Zealand Society of
      Nephrology, 7-9 September 2015, National Convention Centre, Canberra, Australia.

PMID- 26293374
TI  - Renal Genetics Interest Group - 3rd Annual Renal Genetics Symposium.

PMID- 26293376
TI  - Adjuvant Therapy for Gallbladder Cancer: an Analysis of the National Cancer Data
      Base.
AB  - BACKGROUND: The role of adjuvant therapy in patients with resected gallbladder
      cancer (GBC) is unclear. METHODS: The American College of Surgeons National
      Cancer Data Base was used to identify patients with resected GBC (pathologic
      stage 1-3) from 1998 to 2006 (n = 6690). We compared three groups: surgery only
      (S, 78.6 %), surgery plus adjuvant chemotherapy (AC, 6.2 %), and surgery plus
      adjuvant chemotherapy and radiation therapy (ACR, 15.1 %). Univariate and Cox
      regression analyses were used to determine factors influencing overall survival
      and the use of adjuvant therapy. RESULTS: ACR was associated with improved
      survival for all patients (HR 0.77, 95 % CI 0.66-0.90), especially node-positive
      patients (HR 0.64, 95 % CI 0.53-0.78); AC was not associated with changes in
      survival. Patients were less likely to have their lymph nodes examined if they
      had any comorbidities, lower income, or were treated at community cancer centers
      (all p < 0.05). Among patients with unknown lymph node status, those with T2 or
      T3 disease saw improved survival with ACR (T2: HR 0.79, 95 % CI 0.63-0.99; T3: HR
      0.43, 95 % CI 0.30-0.62), while AC did not affect survival. CONCLUSION: ACR is
      associated with improved survival for patients with node-positive GBC, as well as
      those with T2 or T3 GBC with unknown lymph node status.

PMID- 26293377
TI  - Gene-expression analysis of matrix metalloproteinases 1 and 2 and their tissue
      inhibitors in chronic periapical inflammatory lesions.
AB  - BACKGROUND: Periapical inflammatory lesions have been investigated previously,
      but understanding of pathogenesis of these lesions (granulomas and radicular
      cysts) at the molecular level is still questionable. Matrix metalloproteinases
      (MMPs) are enzymes involved in the development of periapical pathology,
      specifically inflammation and tissue destruction. To elucidate pathogenesis of
      periapical granulomas and radicular cysts, we undertook a detailed analysis of
      gene expression of MMP-1, MMP-2 and their tissue inhibitors, TIMP-1 and TIMP-2.
      METHODS: A total of 149 samples were analyzed using real-time PCR (59 radicular
      cysts, 50 periapical granulomas and 40 healthy gingiva samples as controls) for
      expression of MMP-1, MMP-2, TIMP-1 and TIMP-2 genes. The determination of best
      reference gene for expression analysis of periapical lesions was done using a
      panel of 12 genes. RESULTS: We have shown that beta-actin and GAPDH are not the
      most stable reference controls for gene expression analysis of inflammatory
      periapical tissues and healthy gingiva. The most suitable reference gene was
      determined to be SDHA (a succinate dehydrogenase complex, subunit A, flavoprotein
      [Fp]). We found that granulomas (n = 50) and radicular cysts (n = 59) exhibited
      significantly higher expression of all four examined genes, MMP-1, MMP-2, TIMP-1,
      and TIMP-2, when compared to healthy gingiva (n = 40; P < 0.05). CONCLUSION: This
      study has confirmed that the expression of MMP-1, MMP-2, TIMP-1, and TIMP-2 genes
      is important for the pathogenesis of periapical inflammatory lesions. Since the
      abovementioned markers were not differentially expressed in periapical granulomas
      and radicular cysts, the challenge of finding the genetic differences between the
      two lesions still remains.

PMID- 26293379
TI  - Management of pulmonary toxicity associated with targeted anticancer therapies.
AB  - INTRODUCTION: Targeted anticancer therapies act by interfering with defined
      molecular entities and/or biologic pathways. Because of their more specific
      mechanism of action, adverse events (AEs) on healthy tissues are intended to be
      minimal, resulting in a different toxicity profile from that observed with
      conventional cytotoxic chemotherapy. Pulmonary AEs are rare but potentially life
      threatening and it is, therefore, critical to recognize early on and manage
      appropriately. AREAS COVERED: In this review, we aim to offer an overview of both
      more frequent and rare pulmonary AEs caused by targeted anticancer therapies and
      discuss possible treatment algorithms. Anti-vascular endothelial growth factor,
      anti-human epidermal growth factor receptor and anti-CD20 therapy will be
      reviewed, as well as immune checkpoint inhibitors, anaplastic lymphoma kinase
      inhibitors and mammalian target of rapamycin inhibitors. EXPERT OPINION: Novel
      agents used in the treatment of cancer have specific side-effects, the result of
      allergic reactions, on-target and off-target effects. Clinical syndromes
      associated with pulmonary toxicity vary from bronchospasms, hypersensitivity
      reactions, pneumonitis, acute respiratory distress, lung bleeding, pleural
      effusion to pneumothorax. Knowledge of risk factors, a high index of suspicion
      and a complete diagnostic work-up are essential for limiting the risk of these
      events becoming life threatening. The development of treatment algorithms is
      extremely helpful in managing these events. It is probable that these toxicities
      will be even more frequent with the introduction of combination therapies with
      the obvious challenge of discerning the responsible agent.

PMID- 26293378
TI  - Plk1 relieves centriole block to reduplication by promoting daughter centriole
      maturation.
AB  - Centrosome overduplication promotes mitotic abnormalities, invasion and
      tumorigenesis. Cells regulate the number of centrosomes by limiting centriole
      duplication to once per cell cycle. The orthogonal orientation between a mother
      and a daughter centriole, established at the time of centriole duplication, is
      thought to block further duplication of the mother centriole. Loss of orthogonal
      orientation (disengagement) between two centrioles during anaphase is considered
      a licensing event for the next round of centriole duplication. Disengagement
      requires the activity of Polo-like kinase 1 (Plk1), but how Plk1 drives this
      process is not clear. Here we employ correlative live/electron microscopy and
      demonstrate that Plk1 induces maturation and distancing of the daughter
      centriole, allowing reduplication of the mother centriole even if the original
      daughter centriole is still orthogonal to it. We find that mother centrioles can
      undergo reduplication when original daughter centrioles are only ~80 nm apart,
      which is the distance centrioles normally reach during prophase. 

PMID- 26293380
TI  - Low-dose fludarabine with or without darbepoetin alfa in patients with chronic
      lymphocytic leukemia and comorbidity: primary results of the CLL9 trial of the
      German CLL Study Group.
AB  - This study was planned as a phase 3 trial to investigate low-dose fludarabine
      with or without darbepoetin alfa in older patients with previously untreated or
      treated chronic lymphocytic leukemia (CLL) and comorbidity. Due to slow
      recruitment, the study was terminated prematurely after accrual of 97 patients
      who, on average, were 74 years old and had a cumulative illness rating scale
      (CIRS) total score of 5. We report toxicity and efficacy of the study treatment.
      Grade 3-5 neutropenia and infection were observed in 25% and 10% of patients,
      respectively. Response was seen in 73% (5% complete remissions). Median event
      free and overall survival was 12.2 and 44.8 months, respectively. No differences
      in outcome were found for patients treated with versus without darbepoetin alfa.
      In subjects with progressive/recurrent CLL during or after study treatment,
      overall survival was similar for patients receiving chemotherapy versus
      chemoimmunotherapy as salvage treatment. 

PMID- 26293382
TI  - Shame-based appeals in a tobacco control public health campaign: potential harms
      and benefits.

PMID- 26293383
TI  - Is it not time to reveal the secret sauce of nicotine addiction?

PMID- 26293386
TI  - Correction to Formation of Giant Unilamellar Proteo-Liposomes by Osmotic Shock.

PMID- 26293387
TI  - Highly Transparent, Visible-Light Photodetector Based on Oxide Semiconductors and
      Quantum Dots.
AB  - Highly transparent phototransistors that can detect visible light have been
      fabricated by combining indium-gallium-zinc oxide (IGZO) and quantum dots (QDs).
      A wide-band-gap IGZO film was used as a transparent semiconducting channel, while
      small-band-gap QDs were adopted to absorb and convert visible light to an
      electrical signal. Typical IGZO thin-film transistors (TFTs) did not show a
      photocurrent with illumination of visible light. However, IGZO TFTs decorated
      with QDs showed enhanced photocurrent upon exposure to visible light. The device
      showed a responsivity of 1.35*10(4) A/W and an external quantum efficiency of
      2.59*10(4) under illumination by a 635 nm laser. The origin of the increased
      photocurrent in the visible light was the small band gap of the QDs combined with
      the transparent IGZO films. Therefore, transparent phototransistors based on IGZO
      and QDs were fabricated and characterized in detail. The result is relevant for
      the development of highly transparent photodetectors that can detect visible
      light.

PMID- 26293381
TI  - Inhibitor development in non-severe haemophilia across Europe.
AB  - Evidence about inhibitor formation in non-severe haemophilia and the potential
      role for clotting factor concentrate type is scant. It was the aim of this study
      to report inhibitor development in non-severe haemophilia patients enrolled in
      the European Haemophilia Safety Surveillance (EUHASS) study. Inhibitors are
      reported quarterly and total treated patients annually. Incidence rates and 95%
      confidence intervals (95% CI) were calculated according to diagnosis and
      concentrate used. Between 1-10-2008 and 31-12-2012, 68 centres reported on 7,969
      patients with non-severe haemophilia A and 1,863 patients with non-severe
      haemophilia B. For haemophilia A, 37 inhibitors occurred in 8,622 treatment
      years, resulting in an inhibitor rate of 0.43/100 treatment years (95% CI 0.30
      0.59). Inhibitors occurred at a median age of 35 years, after a median of 38
      exposure days (EDs; P25-P75: 20-80); with 72% occurring within the first 50 EDs.
      In haemophilia B, one inhibitor was detected in 2,149 treatment years, resulting
      in an inhibitor rate of 0.05/100 years (95% CI 0.001-0.26). This inhibitor
      developed at the age of six years, after six EDs. The rate of inhibitors appeared
      similar across recombinant and plasma derived factor VIII (FVIII) concentrates.
      Rates for individual concentrates could not be calculated at this stage due to
      low number of events. In conclusion, inhibitors in non-severe haemophilia occur
      three times more frequently than in previously treated patients with severe
      haemophilia at a rate of 0.43/100 patient years (haemophilia A) and 0.05/100
      years (haemophilia B). Although the majority of inhibitors developed in the first
      50 EDs, inhibitor development continued with increasing exposure to FVIII.

PMID- 26293388
TI  - Vision Amniotic Leak Detector (ALD) to Eliminate Amniotic Fluid Leakage as a
      Cause of Vaginal Wetness in Pregnancy: A NICE Medical Technology Guidance.
AB  - In prelabour rupture of membranes (PROM) or preterm PROM the amniotic membranes
      rupture prior to labour. Where this is not overt a speculum examination is
      undertaken to confirm diagnosis. The Vision Amniotic Leak Detector (ALD) is a
      panty liner that can diagnose amniotic fluid as a cause of vaginal wetness. It
      was evaluated by the UK National Institute for Health and Care Excellence (NICE)
      as part of the Medical Technologies Evaluation Programme. The sponsor
      (CommonSense Ltd) identified five studies, of which three were deemed within
      scope by the External Assessment Centre (EAC). Two of these three used an
      inappropriate comparator. The EAC recalculated the diagnostic accuracy of Vision
      ALD using speculum examination as the comparator: sensitivity of 97% (95% CI 93
      99%), negative predictive value of 96% (95% CI 92-98%). A negative result would
      therefore allow patients to be discharged with confidence. In the sponsor's cost
      consequence model only patients with a positive Vision ALD result would have a
      speculum examination, producing a cost saving of around L10 per patient. The EAC
      felt that some costs were unjustified and the model did not include infection
      outcomes or use in a community setting. The EAC revised the sponsor's model and
      found the results were most sensitive to clinician costs. Vision ALD was
      associated with savings of around L15-L25 per patient when administration in
      lower-cost community healthcare avoided a referral to a higher-cost secondary
      care centre. NICE published guidance MTG15 in July 2013 recommending that the
      case for adopting Vision ALD was supported by the evidence.

PMID- 26293389
TI  - Sherlock 3CG((r)) Tip Confirmation System for Placement of Peripherally Inserted
      Central Catheters: A NICE Medical Technology Guidance.
AB  - In current clinical practice, peripherally inserted central catheters (PICCs) are
      typically inserted using external anatomical measurements and a confirmatory
      chest X-ray, or using fluoroscopy. The Sherlock 3CG((r)) Tip Confirmation System
      (TCS) allows magnetic tracking of the PICC tip during insertion and confirmation
      of the final location using ECG, meaning that most patients will not require a
      chest X-ray or fluoroscopy. The Sherlock 3CG((r)) TCS was evaluated in 2014 by
      the UK National Institute for Health and Care Excellence (NICE) as part of the
      Medical Technologies Evaluation Programme. The company (C.R. Bard Ltd) identified
      four abstracts, one paper pending publication and questionnaire data from NHS
      users of the Sherlock 3CG((r)) TCS. None of the evidence included a comparator
      arm. Placement accuracy of PICCs using the Sherlock 3CG((r)) TCS where a chest X
      ray was also used ranged from 79.5 to 100 %. The company reported that 9 out of
      16 NHS centres that used the Sherlock 3CG((r)) TCS were no longer using chest X
      rays to routinely confirm PICC tip location. The evidence did not report the need
      for catheter repositioning, re-insertion, staff time savings, treatment delays,
      length of stay, quality of life outcomes or complications. The company's model
      found that the Sherlock 3CG((r)) TCS was cost saving by GBP25.67 per patient
      compared to blind bedside PICC insertion. The External Assessment Centre (EAC)
      adapted the company's model to test alternative assumptions for nurse time,
      theatre cost, malposition rate and reinsertion method, and found that the
      Sherlock 3CG((r)) TCS was cost incurring by GBP9.37 per patient compared to blind
      bedside PICC insertion. The use of the Sherlock 3CG((r)) TCS in the UK NHS
      compared to blind PICC insertion using a confirmatory chest X-ray appears to
      hover around being cost neutral. Staff time and accuracy were key drivers in the
      model: evidence for these is sparse and the reality will vary in different
      situations. If evidence became available for outcomes after the initial
      insertion, such as replacement, complications and adverse events, the cost
      implications may change. The direction of this potential change is not known.
      NICE published guidance MTG24 in March 2015 recommending that the case for
      adoption of Sherlock 3CG((r)) TCS was supported by the evidence. 

PMID- 26293391
TI  - Inflammation and Atherosclerosis Are Associated With Hypertension in Kidney
      Transplant Recipients.
AB  - The aim of the current study was to evaluate risk factors associated with
      hypertension in kidney transplant recipients. The authors recruited 92
      consecutive kidney transplant recipients and 30 age-matched patients with chronic
      kidney disease without history of cardiovascular events. Twenty-four-hour
      ambulatory blood pressure monitoring, pulse wave velocity, and carotid ultrasound
      were performed. Serum levels of log-transformed interleukin 6 (Log IL-6), soluble
      tumor necrosis factor receptor 2, and intercellular adhesion molecule 1 were
      determined. Twenty-four-hour systolic blood pressure (SBP) (P=.0001), Log IL-6
      (P=.011), and total number of carotid plaques (P=.013) were higher, while the
      percentage decline of SBP from day to night was lower in kidney transplant
      recipients (P=.003). Independent predictors of 24-hour SBP were urinary
      protein/creatinine ratio and circulating monocytes (P=.001), while Log IL-6,
      serum creatinine, and total number of carotid plaques (P=.0001) were independent
      predictors of percentage decline of SBP from day to night. These results suggest
      that subclinical atherosclerosis and systemic inflammation are associated with
      hypertension after transplantation. 

PMID- 26293405
TI  - Therapeutic advances in tremor.
AB  - Although tremor is a highly prevalent movement disorder, progress in this field
      is limited because of the poor understanding of many of the underlying
      conditions. This review summarizes recent treatment attempts since 2013. For
      essential tremor, recent innovations are phase I or II studies of Octanol,
      several clinically relevant refinements for deep brain stimulation, and the
      development of the new magnetic resonance imaging guided focused ultrasound
      technique. Further new invasive and noninvasive electrical and magnetic
      stimulation techniques have been tested for essential tremor and parkinsonian
      tremor. For multiple sclerosis tremor, some open-label observations have shown
      positive results (natalizumab, dalfampridine, levetiracetam), whereas controlled
      trials using cannabinoids have been negative. Functional tremor has shown a
      positive response to retrainment. Neuroprosthetic devices have been tested in a
      variety of tremor conditions. Several promising medical and surgical treatment
      trials are underway and will be completed shortly.

PMID- 26293390
TI  - Screening for cystic fibrosis in New York State: considerations for algorithm
      improvements.
AB  - Newborn screening for cystic fibrosis (CF), a chronic progressive disease
      affecting mucus viscosity, has been beneficial in both improving life expectancy
      and the quality of life for individuals with CF. In New York State from 2007 to
      2012 screening for CF involved measuring immunoreactive trypsinogen (IRT) levels
      in dried blood spots from newborns using the IMMUCHEM(TM) Blood Spot Trypsin-MW
      ELISA kit. Any specimen in the top 5% IRT level underwent DNA analysis using the
      InPlex((r)) CF Molecular Test. Of the 1.48 million newborns screened during the 6
      year time period, 7631 babies were referred for follow-up. CF was confirmed in
      251 cases, and 94 cases were diagnosed with CF transmembrane conductance
      regulated-related metabolic syndrome or possible CF. Nine reports of false
      negatives were made to the program. Variation in daily average IRT was observed
      depending on the season (4-6 ng/ml) and kit lot (<3 ng/ml), supporting the use of
      a floating cutoff. The screening method had a sensitivity of 96.5%, specificity
      of 99.6%, positive predictive value of 4.5%, and negative predictive value of
      99.5%. CONCLUSION: Considerations for CF screening algorithms should include IRT
      variations resulting from age at specimen collection, sex, race/ethnicity,
      season, and manufacturer kit lots. WHAT IS KNOWN: Measuring IRT level in dried
      blood spots is the first-tier screen for CF. Current algorithms for CF screening
      lead to substantial false-positive referral rates. WHAT IS NEW: IRT values were
      affected by age of infant when specimen is collected, race/ethnicity and sex of
      infant, and changes in seasons and manufacturer kit lots The prevalence of CF in
      NYS is 1 in 4200 with the highest prevalence in White infants (1 in 2600) and the
      lowest in Black infants (1 in 15,400).

PMID- 26293406
TI  - Dual-chamber pacemakers for treating symptomatic bradycardia due to sick sinus
      syndrome without atrioventricular block: a systematic review and economic
      evaluation.
AB  - BACKGROUND: Bradycardia [resting heart rate below 60 beats per minute (b.p.m.)]
      can be caused by conditions affecting the natural pacemakers of the heart, such
      as sick sinus syndrome (SSS) and atrioventricular (AV) blocks. People suffering
      from bradycardia may present with palpitations, exercise intolerance and
      fainting. The only effective treatment for patients suffering from symptomatic
      bradycardia is implantation of a permanent pacemaker. OBJECTIVE: To appraise the
      clinical effectiveness and cost-effectiveness of dual-chamber pacemakers compared
      with single-chamber atrial pacemakers for treating symptomatic bradycardia in
      people with SSS and no evidence of AV block. DATA SOURCES: All databases
      (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Health
      Technology Assessment database, NHS Economic Evaluations Database) were searched
      from inception to June 2014. METHODS: A systematic review of the clinical and
      economic literature was carried out in accordance with the general principles
      published by the Centre for Reviews and Dissemination. Randomised controlled
      trials (RCTs) evaluating dual-chamber and single-chamber atrial pacemakers and
      economic evaluations were included. Pairwise meta-analysis was carried out. A de
      novo economic model was developed. RESULTS: Of 493 references, six RCTs were
      included in the review. The results were predominantly influenced by the largest
      trial DANPACE. Dual-chamber pacing was associated with a statistically
      significant reduction in reoperation [odds ratio (OR) 0.48, 95% confidence
      interval (CI) 0.36 to 0.63] compared with single-chamber atrial pacing. The
      difference is primarily because of the development of AV block requiring upgrade
      to a dual-chamber device. The risk of paroxysmal atrial fibrillation was also
      reduced with dual-chamber pacing compared with single-chamber atrial pacing (OR
      0.75, 95% CI 0.59 to 0.96). No statistically significant difference was found
      between the pacing modes for mortality, heart failure, stroke, chronic atrial
      fibrillation or quality of life. However, the risk of developing heart failure
      may vary with age and device. The de novo economic model shows that dual-chamber
      pacemakers are more expensive and more effective than single-chamber atrial
      devices, resulting in a base-case incremental cost-effectiveness ratio (ICER) of
      L6506. The ICER remains below L20,000 in probabilistic sensitivity analysis,
      structural sensitivity analysis and most scenario analyses and one-way
      sensitivity analyses. The risk of heart failure may have an impact on the
      decision to use dual-chamber or single-chamber atrial pacemakers. Results from an
      analysis based on age (> 75 years or <= 75 years) and risk of heart failure
      indicate that dual-chamber pacemakers dominate single-chamber atrial pacemakers
      (i.e. are less expensive and more effective) in older patients, whereas dual
      chamber pacemakers are dominated by (i.e. more expensive and less effective)
      single-chamber atrial pacemakers in younger patients. However, these results are
      based on a subgroup analysis and should be treated with caution. CONCLUSIONS: In
      patients with SSS without evidence of impaired AV conduction, dual-chamber
      pacemakers appear to be cost-effective compared with single-chamber atrial
      pacemakers. The risk of developing a complete AV block and the lack of tools to
      identify patients at high risk of developing the condition argue for the
      implantation of a dual-chamber pacemaker programmed to minimise unnecessary
      ventricular pacing. However, considerations have to be made around the risk of
      developing heart failure, which may depend on age and device. STUDY REGISTRATION:
      This study is registered as PROSPERO CRD42013006708. FUNDING: The National
      Institute for Health Research Health Technology Assessment programme.

PMID- 26293407
TI  - Post-Ebolavirus disease syndrome: what do we know?
AB  - As the current Zaire ebolavirus disease outbreak in West Africa fades, the health
      problems of the more than 16,500 survivors have come to light. A wide range of
      mental and physical symptoms may occur during the convalescence stage. Reported
      symptoms of "post-Ebolavirus disease syndrome" (PEVDS) include chronic joint and
      muscle pain, fatigue, anorexia, hearing loss, blurred vision, headache, sleep
      disturbances, low mood and short-term memory problems. PEVDS has been associated
      with a decrease in functionality and difficulties to return to work. Further
      studies are needed to fully categorize the clinical spectrum of PEVDS. Diagnostic
      criteria and surrogate markers for the early diagnosis of PEVDS, and
      implementation of specialized health services to treat and follow-up survivors
      are also needed. 

PMID- 26293408
TI  - Rhodium Complex and Enzyme Couple Mediated Electrochemical Detection of
      Adenosine.
AB  - Adenosine is one of the nucleoside which plays an important role in signal
      transduction and neuromodulation. This work proposes a simple electrochemical
      assay, comprising two enzymes and rhodium complex based electron transfer
      mediator, for the detection of adenosine. Sequential reaction of adenosine
      deaminase and L-glutamic dehydrogenase and the supporting cycle between beta-NADH
      and mediator enable quantitative analysis of adenosine. Role of electron transfer
      mediator is the conveyance of proton from electrode to beta-NAD(+) for
      regeneration of beta-NADH. The electrochemical characteristics of electron
      transfer mediator were also studied. Real-time adenosine detection was carried
      out using this multiple enzyme based chronoamperometric assay. The analysis
      results show a low limit of detection (140 MUM) and good correspondence between
      current signal and the adenosine concentration (R (2) = 0.997).

PMID- 26293409
TI  - Lactic Acid and Biosurfactants Production from Residual Cellulose Films.
AB  - The increasing amounts of residual cellulose films generated as wastes all over
      the world represent a big scale problem for the meat industry regarding to
      environmental and economic issues. The use of residual cellulose films as a
      feedstock of glucose-containing solutions by acid hydrolysis and further
      fermentation into lactic acid and biosurfactants was evaluated as a method to
      diminish and revalorize these wastes. Under a treatment consisting in sulfuric
      acid 6% (v/v); reaction time 2 h; solid liquid ratio 9 g of film/100 mL of acid
      solution, and temperature 130  degrees C, 35 g/L of glucose and 49% of
      solubilized film was obtained. From five lactic acid strains, Lactobacillus
      plantarum was the most suitable for metabolizing the glucose generated. The
      process was scaled up under optimized conditions in a 2-L bioreactor, producing
      3.4 g/L of biomass, 18 g/L of lactic acid, and 15 units of surface tension
      reduction of a buffer phosphate solution. Around 50% of the cellulose was
      degraded by the treatment applied, and the liqueurs generated were useful for an
      efficient production of lactic acid and biosurfactants using L. plantarum.
      Lactobacillus bacteria can efficiently utilize glucose from cellulose films
      hydrolysis without the need of clarification of the liqueurs.

PMID- 26293410
TI  - Early intervention and identification strategies for young people at risk of
      developing mental health issues: working in partnership with schools in
      Birmingham, UK.
AB  - AIM: This study explores the mental health needs of teachers and how these might
      impact on their capacity to provide early identification and intervention
      strategies to support their student's emotional well-being. METHOD: The present
      study surveyed a sample of UK teachers (N = 320) to explore the impact of work
      related stress on their mental health and their ability to provide early
      intervention support for their students. RESULTS: Our survey showed high levels
      of work-related stress due to time pressures and excessive workloads; many
      teachers failed to seek help for their stress often due to stigmatic attitudes
      and fear of negative response by senior management. Such factors led some to
      withdraw from taking on extra responsibilities with regard to student support and
      to consider leaving the teaching profession altogether. Coping mechanisms
      included the use of alcohol and tobacco, with only a small minority receiving
      access to psychological therapies. CONCLUSION: High levels of work-related stress
      in teachers can have serious consequences for their mental health and impede
      their ability to provide effective early intervention support for their student's
      emotional well-being. Improvements in mental health training for teachers and
      greater assistance for their own mental health needs are necessary.

PMID- 26293411
TI  - Synthetic Cannabinoid Abuse in Adolescents: A Case Series.
AB  - BACKGROUND: Synthetic cannabinoids, referred to as "Bonzai" in Turkey, are
      relatively new recreational drugs of abuse. Although the use of synthetic
      cannabinoids has been dramatically increasing in young populations in many
      countries, their adverse effects are not well known. OBJECTIVES: To report on the
      clinical features and social history of pediatric patients with a diagnosis of
      synthetic cannabinoid intoxication and to highlight the dangers of these drugs to
      public health. METHODS: We retrospectively reviewed 16 cases presenting to our
      Emergency Department (ED) with synthetic cannabinoid intoxication in the last 10
      months. Usage characteristics and the psychoactive, physical, and metabolic
      effects of synthetic cannabinoids were analyzed. RESULTS: The mean age of the 16
      patients with a diagnosis of synthetic cannabinoid intoxication was 15.4 +/- 1.7
      years (15 males, 1 female). The most common physical symptoms were eye redness,
      nausea/vomiting, sweating, and altered mental status; the main psychoactive
      findings were agitation, anxiety, hallucinations, and perceptual changes. We
      observed hypotension and bradycardia in 8 (50%) and 5 (31.3%) of the patients,
      respectively. Although most patients were discharged from the ED, 25% were
      transferred to an intensive care unit. They all had reduced school attendance and
      performance. The rates of cigarette smoking and alcohol drinking were also
      significantly higher. CONCLUSION: Synthetic cannabinoids are unsafe and
      potentially harmful drugs of abuse; they may even cause life-threatening effects.
      It is important for pediatricians to be familiar with the signs and symptoms of
      consumption of synthetic cannabinoid products. Education of parents, teachers,
      and adolescents about the potential health risks of using these products is
      essential.

PMID- 26293412
TI  - Emergency Hospital Admissions for Initial Febrile Urinary Tract Infection: Do
      Patient Demographics Matter?
AB  - BACKGROUND: In 2011, the American Academy of Pediatrics revised practice
      parameters regarding febrile urinary tract infection (fUTI) in children aged 2-24
      months. The Section on Urology opposed the omission of voiding cystourethrogram
      (VCUG), and expressed concern that potential untoward consequences of deferring
      VCUG may be most felt by children on Medicaid. OBJECTIVE: We ascertained imaging
      and characteristics of children presenting to the Emergency Department (ED) with
      initial fUTI to determine the impact of patient demographics on admissions for
      pyelonephritis. METHODS: Children aged 2-24 months presenting to the ED with
      initial fUTI were identified. Demographics, insurance status, laboratory studies,
      renal-bladder ultrasound (RBUS), VCUG, and hospital admission status were
      evaluated. RESULTS: Three-hundred fifty patients met inclusion criteria; 88
      (25.1%) were admitted. Admitted patients were significantly (p < 0.001) younger
      (mean 0.31 +/- 0.33 years) than those managed as outpatients (mean 0.91 +/- 0.7
      years). On univariate analysis, male gender (p < 0.001), Medicaid insurance (p <
      0.05), and non-Hispanic race (p < 0.05) were associated with admission. Race
      retained significance on multivariate analysis; Caucasian children were 2.35
      times (95% confidence interval [CI] 0.79-7.23) and African-American children 3.8
      times more likely to be admitted than Hispanic patients (95% CI 1.88-7.63).
      Children with abnormal RBUS were 12.8 times more likely to require admission (95%
      CI 4.44-37.0). Medicaid was also independently predictive of admission; such
      patients were 2.6 times more likely to be admitted than those with private
      insurance (95% CI 1.15-5.88). CONCLUSIONS: Abnormal ultrasound, non-Hispanic
      race, and public insurance were strongly associated with hospital admission in
      children presenting to the ED with initial febrile urinary tract infection.

PMID- 26293413
TI  - M-Mode Ultrasound Applications for the Emergency Medicine Physician.
AB  - BACKGROUND: M-mode or "motion" mode is a form of ultrasound imaging that is of
      high clinical utility in the emergency department. It can be used in a variety of
      situations to evaluate motion and timing, and can document tissue movement in a
      still image when the recording of a video clip is not feasible. OBJECTIVES: In
      this article we describe several straightforward and easily performed
      applications for the emergency physician to incorporate M-mode into his or her
      practice, including the evaluation for: 1) pneumothorax, 2) left ventricular
      systolic function, 3) cardiac tamponade, and 4) hypertrophic cardiomyopathy.
      DISCUSSION: The emergency physician and other point-of-care ultrasound providers
      can use this versatile function in the evaluation of patients for a number of
      critical cardiopulmonary diagnoses. CONCLUSION: A great deal of important
      information may be obtained with M-mode imaging through views and measurements
      that are relatively easy to obtain.

PMID- 26293415
TI  - [Radiation therapy and immunomodulation: Focus on experimental data].
AB  - The immunosuppressive effects of radiation therapy have long been the only ones
      considered. It has been demonstrated that exposure to ionizing radiation induces
      the release of tumour antigens which activates both the innate immune system and
      the adaptive immune response of the host. The purpose of tumour immunotherapy is
      based on the principle that reversal of tolerance to immunogenic tumours would be
      able to activate an immune response against tumour cells. Preclinical data and
      clinical studies early phase suggest a potential therapeutic benefit of
      immunotherapy combined with radiation therapy. The objective of this article is
      to review how tumour cells interact with the immune system and how ionizing
      radiation modulate this interaction and finally the combination of perspectives
      of immunotherapy and ionizing radiation by focusing on existing clinical data. 

PMID- 26293416
TI  - Multimodal cancer imaging using lanthanide-based upconversion nanoparticles.
AB  - Multimodal nanoprobes that integrate different imaging modalities in one nano
      system could offer synergistic effect over any modality alone to satisfy the
      higher requirements on the efficiency and accuracy for clinical diagnosis and
      medical research. Upconversion nanoparticles (UCNPs), particularly lanthanide
      (Ln)-based NPs have been regarded as an ideal building block for constructing
      multimodal bioprobes due to their fascinating properties. In this review, we
      first summarize recent advances in the optimizations of existing UCNPs. In
      particular, we highlight the applications of Ln-based UCNPs for multimodal cancer
      imaging in vitro and in vivo. The explorations of UCNPs-based multimodal
      nanoprobes for targeting diagnosis and imaging-guided therapeutics are also
      presented. Finally, the challenges and perspectives of Ln-based UCNPs in this
      rapid growing field are discussed. 

PMID- 26293417
TI  - Trends in stroke admission and mortality rates from 1983 to 2013 in central
      Ghana.
AB  - BACKGROUND: Accumulating data based on model-derived estimates suggest rising
      rates of stroke in sub-Saharan Africa over the next several decades. Stroke is a
      leading cause of death, disability, and dementia worldwide. Directly enumerated
      hospital-based data on the longitudinal trajectory of stroke admissions and
      deaths in sub-Saharan Africa could help hospital administrators, public health
      officials, and government policy-makers with planning and utilization of scarce
      resources. OBJECTIVE: To evaluate 30-year trends in stroke admission and
      mortality rates in central Ghana. METHODS: We undertook a retrospective analysis
      of data on stroke admissions and mortality at a tertiary referral hospital in
      central Ghana between 1983 and 2013. Rates of stroke admissions and mortality
      were expressed as stroke admissions or deaths divided by total number of hospital
      admissions or deaths respectively. Yearly crude case fatality from stroke was
      calculated and predictors of stroke mortality were determined using Cox
      proportional hazards regression analysis. RESULTS: Over the period, there were
      12,233 stroke admissions with equal gender distribution. The rate of stroke
      admissions increased progressively from 5.32/1000 admissions in 1983 to
      13.85/1000 admissions in 2010 corresponding to a 260% rise over the period.
      Stroke mortality rates also increased from 3.40/1000 deaths to 6.66/1000 deaths
      over the 30-year period. The average 28-day mortality over the period was 41.1%.
      Predictors of in-patient mortality were increasing age-aHR of 1.31 (1.16-1.47)
      for age>80years compared with <40years and admissions in 2000's compared with
      1980's; aHR of 1.32 (1.26-1.39). Of the 1132 stroke patients with neuroimaging
      data: 569 (50.3%) had intracerebral hemorrhage, 382 (33.7%) had ischemic stroke
      and 181 (16.0) had sub-arachnoid hemorrhage. Patients with ischemic stroke were
      significantly older than those with ICH and SAH respectively. CONCLUSION: Rates
      of stroke admission and mortality have increased steadily over the past three
      decades in central Ghana. More intensive risk modification and optimization of
      acute stroke care are urgently needed to stem these worrisome trends.

PMID- 26293418
TI  - Serum NSE and multiple sclerosis.

PMID- 26293414
TI  - Mitochondrial function in ageing: coordination with signalling and
      transcriptional pathways.
AB  - Mitochondrial dysfunction entailing decreased energy-transducing capacity and
      perturbed redox homeostasis is an early and sometimes initiating event in ageing
      and age-related disorders involving tissues with high metabolic rate such as
      brain, liver and heart. In the central nervous system (CNS), recent findings from
      our and other groups suggest that the mitochondrion-centred hypometabolism is a
      key feature of ageing brains and Alzheimer's disease. This hypometabolic state is
      manifested by lowered neuronal glucose uptake, metabolic shift in the astrocytes,
      and alternations in mitochondrial tricarboxylic acid cycle function. Similarly,
      in liver and adipose tissue, mitochondrial capacity around glucose and fatty acid
      metabolism and thermogenesis is found to decline with age and is implicated in
      age-related metabolic disorders such as obesity and type 2 diabetes mellitus.
      These mitochondrion-related disorders in peripheral tissues can impact on brain
      functions through metabolic, hormonal and inflammatory signals. At the cellular
      level, studies in CNS and non-CNS tissues support the notion that instead of
      being viewed as autonomous organelles, mitochondria are part of a dynamic network
      with close interactions with other cellular components through energy- or redox
      sensitive cytosolic kinase signalling and transcriptional pathways. Hence, it
      would be critical to further understand the molecular mechanisms involved in the
      communication between mitochondria and the rest of the cell. Therapeutic
      strategies that effectively preserves or improve mitochondrial function by
      targeting key component of these signalling cascades could represent a novel
      direction for numerous mitochondrion-implicated, age-related disorders. 

PMID- 26293419
TI  - High-Intensity Telemedicine Decreases Emergency Department Use for Ambulatory
      Care Sensitive Conditions by Older Adult Senior Living Community Residents.
AB  - BACKGROUND: Emergency department (ED) visits for ambulatory care sensitive
      conditions (ACSCs) are common among older adults. The high-intensity telemedicine
      model of care has been proposed as an innovative approach to expand access to
      acute illness care, thereby preventing ED visits. The aim of this study was to
      assess the effect of a high-intensity telemedicine program for senior living
      community (SLC) residents on the rate of ED use for ACSCs. METHODS: We performed
      a prospective cohort study at a primary care geriatrics practice that provides
      care to 22 SLCs. Six SLCs selected as intervention facilities, with the remaining
      SLCs serving as controls. Consenting practice patients at intervention facilities
      could have patient-to-provider, real-time, or store-and-forward high-intensity
      telemedicine services to diagnose and treat illnesses. The primary outcome was
      the rate of ED visits for which the primary diagnosis was an "ambulatory-care
      sensitive" condition by the Institute of Medicine, which we compared between
      control and intervention participants. RESULTS: During the study period, control
      participants had 310 ED visits for ACSCs, for a rate of 0.195 visits/person-year.
      Intervention participants visited the ED for ACSCs 85 times, for a rate of 0.138
      visits/person-year [unadjusted rate ratio (RR): 0.71, 95% confidence interval
      (CI): 0.53-0.94]. Among intervention participants, ED use for ACSCs decreased at
      an annual rate of 34% (RR: 0.661, 95% CI: 0.444-0.982), whereas, in the control
      group there was no statistically significant change in ED use over time (RR:
      1.01, 95% CI: 0.90-1.14). CONCLUSIONS: Providing acute illness care by high
      intensity telemedicine to older adults residing in SLCs significantly decreases
      the rate of ED use for ACSCs over 1 year, compared with no change in the rate of
      ED use for ACSCs among the control group.

PMID- 26293420
TI  - Polypharmacy in Nursing Home Residents: What Is the Way Forward?

PMID- 26293421
TI  - Bipedality from locomotor autonomy to adulthood in captive olive baboon (Papio
      anubis): Cross-sectional follow-up and first insight into the impact of body mass
      distribution.
AB  - OBJECTIVE: Despite that the biomechanics of standing and walking bipedally has
      been extensively studied in nonhuman primates, the morphological features that
      may constrain, or facilitate, the control of balance and thus of the spontaneous
      occurrence of bipedal behavior are poorly known. We aim to test the relationship
      between body mass distribution and bipedal behavior using a nonhuman primate
      species, the olive baboon, Papio anubis, raised in captivity. MATERIALS AND
      METHODS: We collected quantitative data on the frequency and duration of
      bipedalism together with morphometrics on a sample of 22 individuals. We used
      ontogenetic changes as a natural experiment that provides insights into the
      impact of morphology. Specifically we focus on 1) quantifying how body mass
      distribution changes from infancy to adulthood in baboons; and 2) whether the
      different patterns of mass distribution influence the behavioral variables, i.e.,
      a) the frequency and b) the duration of bouts of bipedal behavior realized in
      different activity contexts. RESULTS: With regard to assisted bipedal behaviors,
      the duration and frequency of bouts of standing, contrary to walking, are
      significantly related to age. With regard to unassisted bipedal behaviors, no
      correlation to age is observed; the bout duration of walking is strongly
      correlated to body mass and mass distribution, contrary to the frequency of
      walking as well as the bout duration and frequency of bipedal standing.
      DISCUSSION: Our results suggest a close relationship between the pattern of mass
      distribution and the mechanism of balance control in the spontaneous bipedal
      walking of baboons. The mechanical effects of the pattern of mass distribution on
      the ability to perform bipedally in extant nonhuman primates are discussed in the
      context of the evolution toward habitual bipedalism.

PMID- 26293422
TI  - Comments about the paper entitled "Lessons to be learned from an analysis of
      ammonium nitrate disasters in the last 100 years" by Pittman et al. (J. Hazard.
      Mater. 280 (2014) 472-477).

PMID- 26293423
TI  - First case of mesh infection due to Coccidioides spp. and literature review of
      fungal mesh infections after hernia repair.
AB  - Fungal mesh infections are a rare complication of hernia repairs with mesh. The
      first case of Coccidioides spp. mesh infection is described, and a systematic
      literature review of all known fungal mesh infections was performed. Nine cases
      of fungal mesh infection are reviewed. Female and male patients are equally
      represented, median age is 49.5 years, and critical illness and preinfection
      antibiotic use were common. Fungal mesh infections are rare, but potentially
      fatal, complications of hernias repaired with mesh.

PMID- 26293424
TI  - Demography still dictates destiny for children with disabilities.

PMID- 26293425
TI  - Keeping sex workers safe.

PMID- 26293426
TI  - Preventing unsafe abortions through task shifting and sharing.

PMID- 26293428
TI  - India's medical education system hit by scandals.

PMID- 26293429
TI  - Key donors to reinstate health funding to Zambia.

PMID- 26293430
TI  - Global surgery.

PMID- 26293431
TI  - Edgar Rodas.

PMID- 26293432
TI  - Infective endocarditis and antibiotic prophylaxis.

PMID- 26293433
TI  - Infective endocarditis and antibiotic prophylaxis.

PMID- 26293434
TI  - Infective endocarditis and antibiotic prophylaxis.

PMID- 26293435
TI  - Infective endocarditis and antibiotic prophylaxis.

PMID- 26293436
TI  - Infective endocarditis and antibiotic prophylaxis.

PMID- 26293437
TI  - Infective endocarditis and antibiotic prophylaxis.

PMID- 26293438
TI  - Infective endocarditis and antibiotic prophylaxis - Authors' reply.

PMID- 26293439
TI  - Department of Error.

PMID- 26293427
TI  - The Vancouver Consensus: antiretroviral medicines, medical evidence, and
      political will.

PMID- 26293441
TI  - Department of Error.

PMID- 26293440
TI  - Department of Error.

PMID- 26293442
TI  - China's medical research integrity.

PMID- 26293443
TI  - A comparative study of different modalities of treatment in nicotine dependence
      syndrome.
AB  - There are different modalities for management of Nicotine dependence, but it is
      still inconclusive which is the best modality for the treatment of Nicotine
      dependence syndrome (NDS). In this background the present study was carried out
      to assess the efficacy and to compare different modalities for the treatment of
      NDS. METHODS: Patients diagnosed as NDS as per ICD-10 were taken up for study.
      These patients were administered proforma to elicit sociodemographic details,
      Fagerstrom test for Nicotine Dependence, Questionnaire of Smoking Urges-Brief and
      breath analysis was done using carbon monoxide meter. Assessment was done at base
      line and at weekly follow-ups for 12 weeks. Patients were divided into six groups
      randomly. Group A received BUP at a dose of 150mg/day for 3 days; subsequently
      increased to 300mg/day, Group B: for initial 6 weeks Nicotine gum of 4mg every 1
      2 hourly was used and next 6 weeks every 2-4 hourly was used, Group C: BI, Group
      D: BI+BUP, Group E: BI+NRT, Group F received BUP+NRT+BI. RESULTS: The quit rates
      at end of the study were BUP-30%, NRT-26.66%, BI-23.33%, BI+BUP-43.33%, BI+NRT
      33.33%, and BI+BUP+NRT-50%. BI+BUP+NRT had 2-3 times more quit rates than the
      individual modality treatment group. CONCLUSION: There was no statistically
      significant difference between the study groups, but there was clinical
      difference in quit rates. Among the groups BI+BUP+NRT had higher quit rates
      compared to other groups. Combination modalities yield better quit rates than
      individual modalities.

PMID- 26293444
TI  - Analyzing Information Seeking and Drug-Safety Alert Response by Health Care
      Professionals as New Methods for Surveillance.
AB  - BACKGROUND: Patterns in general consumer online search logs have been used to
      monitor health conditions and to predict health-related activities, but the
      multiple contexts within which consumers perform online searches make significant
      associations difficult to interpret. Physician information-seeking behavior has
      typically been analyzed through survey-based approaches and literature reviews.
      Activity logs from health care professionals using online medical information
      resources are thus a valuable yet relatively untapped resource for large-scale
      medical surveillance. OBJECTIVE: To analyze health care professionals'
      information-seeking behavior and assess the feasibility of measuring drug-safety
      alert response from the usage logs of an online medical information resource.
      METHODS: Using two years (2011-2012) of usage logs from UpToDate, we measured the
      volume of searches related to medical conditions with significant burden in the
      United States, as well as the seasonal distribution of those searches. We
      quantified the relationship between searches and resulting page views. Using a
      large collection of online mainstream media articles and Web log posts we also
      characterized the uptake of a Food and Drug Administration (FDA) alert via
      changes in UpToDate search activity compared with general online media activity
      related to the subject of the alert. RESULTS: Diseases and symptoms dominate
      UpToDate searches. Some searches result in page views of only short duration,
      while others consistently result in longer-than-average page views. The response
      to an FDA alert for Celexa, characterized by a change in UpToDate search
      activity, differed considerably from general online media activity. Changes in
      search activity appeared later and persisted longer in UpToDate logs. The volume
      of searches and page view durations related to Celexa before the alert also
      differed from those after the alert. CONCLUSIONS: Understanding the information
      seeking behavior associated with online evidence sources can offer insight into
      the information needs of health professionals and enable large-scale medical
      surveillance. Our Web log mining approach has the potential to monitor responses
      to FDA alerts at a national level. Our findings can also inform the design and
      content of evidence-based medical information resources such as UpToDate.

PMID- 26293445
TI  - Effect of new neuronal growth factor on healing of sciatic nerve in rats.
AB  - OBJECTIVE: The study aimed to investigate the effect of a new peptide new nerve
      growth factor (NNGF) on the healing of divided sciatic nerves in rats. MATERIAL
      AND METHODS: Twenty Sprague-Dawley rats of 250-300g were divided into two groups
      (group 1 - study group and group 2 - control group). Under ketamine intramuscular
      anesthesia sciatic nerves were exposed, divided and repaired using 10/0 dexon.
      Study animals had 10mg/kg body weight of NNGF added to the repair.
      Electromyographic studies of the hind libs were carried out after 8weeks. The
      average stimulation was 50mA for 200MUS and four twitches (T) were recorded. The
      animals were euthanized and the sciatic nerves were removed for histological
      analysis. RESULTS: There were no deaths in either of the groups.
      Electromyographic study showed that in the control group the average T1-T4 was
      0.587+/-0.17% and in the study group the average was 87.89+/-5.02% (p value of
      0.001). Histologically the control group showed regenerated axons sprouting from
      the proximal segment of cut nerve with empty endoneurial channels, while in the
      study group whole nerve trunks were seen within endoneurial channels. CONCLUSION:
      This study shows that the NNGF has a positive influence on the experimental
      healing of sciatic nerves in animals.

PMID- 26293446
TI  - How to spend the summer? Free-living dormice (Glis glis) can hibernate for 11
      months in non-reproductive years.
AB  - Edible dormice are arboreal rodents adapted to yearly fluctuations in seed
      production of European beech, a major food source for this species. In years of
      low beech seed abundance, dormice skip reproduction and non-reproductive dormice
      fed ad libitum in captivity can display summer dormancy in addition to winter
      hibernation. To test whether summer dormancy, that is, a very early onset of
      hibernation, actually occurs in free-living dormice, we monitored core body
      temperature (Tb) over ~12 months in 17 animals during a year of beech seeding
      failure in the Vienna Woods. We found that 8 out of 17 dormice indeed re-entered
      hibernation as early as in June/July, with five of them having extreme
      hibernation durations of 11 months or more (total range: 7.8-11.4 months). Thus,
      we show for the first time that a free-living mammal relying on natural food
      resources can continuously hibernate for >11 months. Early onset of hibernation
      was associated with high body mass in the spring, but the distribution of
      hibernation onset was bimodal with prolonged hibernation starting either early
      (prior to July 28) or late (after August 30). This could not be explained by
      differences in body mass alone. Animals with a late hibernation onset continued
      to maintain high nocturnal Tb's throughout summer but used short, shallow torpor
      bouts (mean duration 7.44 +/- 0.9 h), as well as occasional multiday torpor for
      up to 161 h.

PMID- 26293447
TI  - Triggering final follicular maturation--hCG, GnRH-agonist or both, when and to
      whom?
AB  - Controlled ovarian hyperstimulation (COH) which combines GnRH antagonist co
      treatment and GnRH-agonist (GnRHa) trigger has become a common tool aiming to
      eliminate severe early OHSS and to support the concept of an OHSS-free clinic.
      However, due to the reported significantly reduced clinical, efforts have been
      made to improve reproductive outcome. One of the suggested optional strategies
      aiming to improve outcome was the addition of low-dose (1500 IU) HCG bolus,
      administered, concomitant, 35 h or 5 days after the triggering bolus of GnRHa.
      All these regimens were demonstrated to rescue the luteal phase, resulting in
      improved reproductive outcome in patients at risk to develop severe OHSS,
      compared to GnRHa trigger alone, however, with the questionable ability to
      eliminate severe OHSS.Moreover, following the observations demonstrating
      comparable or even better oocyte?embryos quality following GnRHa, compared to hCG
      trigger, and the different effects of LH and hCG on the downstream signaling of
      the LH receptor, GnRHa is now offered concomitant to the standard hCG trigger
      dose to improve oocyte/embryo yield and quality. GnRHa and hCG may be offered
      either concomitantly, 35-37 h prior to oocyte retrieval (dual trigger), or 40 h
      and 34 h prior to oocyte retrieval, respectively (double trigger). 

PMID- 26293448
TI  - Remitting seronegative symmetrical synovitis with pitting edema syndrome in
      individuals with type 2 diabetes mellitus or impaired glucose tolerance.
AB  - An association between remitting seronegative symmetrical synovitis with pitting
      edema (RS3PE) syndrome and insulin or dipeptidyl peptidase-4 (DPP4) inhibitor
      therapy were previously reported. We encountered four cases of RS3PE syndrome
      with type 2 diabetes mellitus or impaired glucose tolerance (IGT) without insulin
      or DPP4 inhibitor medication. 

PMID- 26293449
TI  - Serum omentin-1 levels as a possible risk factor of mortality in patients with
      diabetes on haemodialysis.
AB  - AIM: The main cause of mortality in haemodialysis (HD) patients is cardiovascular
      disease. Serum omentin-1 level was found to be associated with cardio-metabolic
      disorders. The aim of this study was to examine the role of omentin-1 as a
      predictor of mortality in a group of diabetes positive HD patients. METHODS: A
      total of 120 prevalent HD patients were included in the study from December 2012
      to May 2014. Patients were divided into two groups according to the presence or
      absence of diabetes. Venous blood samples were taken at months 0 and 18 following
      an overnight fast (prior to a midweek HD session). Serum omentin-1 level was
      assessed by enzyme-linked immunosorbent assay. RESULTS: A total of 84 HD patients
      were analysed at the end of an 18-month follow-up. Omentin-1 levels of HD
      patients with diabetes were found to be lower than of HD patients without
      diabetes (9.1+/-5.8 ng/mL vs. 11.4+/-4.1 ng/mL, respectively; P=0.015) at the end
      of follow-up. Omentin-1 levels of survived patients with diabetes were found to
      be higher than of nonsurvived patients with diabetes (16.5+/-10.1 ng/mL vs.
      12.9+/-5.3 ng/mL, respectively; P=0.045). During follow-up, 36 patients (30%)
      died, of whom 25 had diabetes (34%). CONCLUSIONS: Serum omentin-1 levels were
      significantly lower in HD patients with diabetes. A decrease in omentin-1 levels
      could be an independent mortality risk factor in this patient group. Further
      investigation in a greater number of patients is needed.

PMID- 26293450
TI  - Acceptance of sexual minorities, discrimination, social capital and health and
      well-being: a cross-European study among members of same-sex and opposite-sex
      couples.
AB  - BACKGROUND: Awareness of health disparities based on sexual orientation has
      increased in the past decades, and many official public health agencies
      throughout Europe call for programs addressing the specific needs of lesbian, gay
      and bisexual (LGB) individuals. However, the acceptance of LGB individuals varies
      significantly in different countries, which potentially influences health and
      well-being in this population. We explored differences in self-rated health and
      subjective well-being between individuals living in same-sex and opposite-sex
      couples. We also examined the effects of discrimination and country-level
      variations in LGB acceptance on health and well-being and the potential mediating
      role of social capital in these associations. METHODS: Using the 2010 European
      Social Survey (n = 50,781), 315 individuals living with a same-sex partner were
      matched and compared with an equal number of individuals living in opposite-sex
      couples. We performed structural equation modeling analyses to estimate path
      coefficients, mediations and interactions. RESULTS: LGB acceptance was
      significantly related to better self-rated health and subjective well-being among
      all individuals, and these associations were partially mediated by individual
      social capital. No differences in these associations were found between
      individuals living in same-sex and opposite-sex couples. Sexuality-based
      discrimination had an additional significantly negative effect on self-related
      health and subjective well-being. CONCLUSIONS: The findings of this study suggest
      a negative association between exposure to discrimination based on sexual
      orientation and both health and well-being of individuals living in same-sex
      couples. Members of same-sex couples and opposite-sex couples alike may benefit
      from living in societies with a high level of LGB acceptance to promote better
      health and well-being.

PMID- 26293451
TI  - Efficacy of add-on therapy of aliskiren to an angiotensin II receptor blocker on
      renal outcomes in advanced-stage chronic kidney disease: a prospective,
      randomized, open-label study.
AB  - BACKGROUND: Combination therapy of aliskiren and an angiotensin II receptor
      blocker (ARB) has been reported to be effective for reducing the level of
      proteinuria. However, it remains unclear whether this combination therapy
      contributes to suppression of kidney disease progression. The aim of this study
      was to investigate the effect of aliskiren on hard renal endpoints, when added to
      an ARB, in patients with advanced chronic kidney disease (CKD). METHODS: The
      study design was a prospective, randomized open-label design. 83 CKD patients (52
      men and 31 women) were enrolled and assigned randomly to an aliskiren add-on
      group (n = 42) or control group (n = 41). Entry criteria included elevated serum
      creatinine >= 1.5 mg/dl, urine protein excretion (>= 1+ on urine dipstick test),
      and hypertension. All participants were treated with an ARB. The follow-up period
      was 12 months. 12 participants were withdrawn during the study period and the
      study was terminated in January 2012 as a consequence of the results of the
      interim analysis of the ALTITUDE study. RESULTS: Nine patients in the aliskiren
      group and seven patients in the control group started dialysis. Doubling of the
      serum creatinine level occurred in one patient in the control group. A Cox
      proportional hazards test showed that dual blockade of the renin-angiotensin
      aldosterone system with aliskiren and ARB was not associated with improvement in
      hard renal endpoints. CONCLUSION: We conclude that aliskiren add-on therapy to an
      ARB may not give any benefit and, therefore, should not be recommended in CKD
      patients.

PMID- 26293452
TI  - Metacognition and evidence analysis instruction: an educational framework and
      practical experience.
AB  - The role of metacognitive skills in the evidence analysis process has received
      little attention in the research literature. While the steps of the evidence
      analysis process are well defined, the role of higher-level cognitive operations
      (metacognitive strategies) in integrating the steps of the process is not well
      understood. In part, this is because it is not clear where and how metacognition
      is implicated in the evidence analysis process nor how these skills might be
      taught. The purposes of this paper are to (a) suggest a model for identifying
      critical thinking and metacognitive skills in evidence analysis instruction
      grounded in current educational theory and research and (b) demonstrate how
      freely available systematic review/meta-analysis tools can be used to focus on
      higher-order metacognitive skills, while providing a framework for addressing
      common student weaknesses. The final goal of this paper is to provide an
      instructional framework that can generate critique and elaboration while
      providing the conceptual basis and rationale for future research agendas on this
      topic.

PMID- 26293453
TI  - Comparing the immune response to a novel intranasal nanoparticle PLGA vaccine and
      a commercial BPI3V vaccine in dairy calves.
AB  - BACKGROUND: There is a need to improve vaccination against respiratory pathogens
      in calves by stimulation of local immunity at the site of pathogen entry at an
      early stage in life. Ideally such a vaccine preparation would not be inhibited by
      the maternally derived antibodies. Additionally, localized immune response at the
      site of infection is also crucial to control infection at the site of entry of
      virus. The present study investigated the response to an intranasal bovine
      parainfluenza 3 virus (BPI3V) antigen preparation encapsulated in PLGA (poly dl
      lactic-co-glycolide) nanoparticles in the presence of pre-existing anti-BPI3V
      antibodies in young calves and comparing it to a commercially available BPI3V
      respiratory vaccine. RESULTS: There was a significant (P < 0.05) increase in
      BPI3V-specific IgA in the nasal mucus of the BPI3V nanoparticle vaccine group
      alone. Following administration of the nanoparticle vaccine an early immune
      response was induced that continued to grow until the end of study and was not
      observed in the other treatment groups. Virus specific serum IgG response to both
      the nanoparticle vaccine and commercial live attenuated vaccine showed a
      significant (P < 0.05) rise over the period of study. However, the cell mediated
      immune response observed didn't show any significant rise in any of the treatment
      groups. CONCLUSION: Calves administered the intranasal nanoparticle vaccine
      induced significantly greater mucosal IgA responses, compared to the other
      treatment groups. This suggests an enhanced, sustained mucosal-based
      immunological response to the BPI3V nanoparticle vaccine in the face of pre
      existing antibodies to BPI3V, which are encouraging and potentially useful
      characteristics of a candidate vaccine. However, ability of nanoparticle vaccine
      in eliciting cell mediated immune response needs further investigation. More
      sustained local mucosal immunity induced by nanoparticle vaccine has obvious
      potential if it translates into enhanced protective immunity in the face of virus
      outbreak.

PMID- 26293455
TI  - Eight in 10 GPs say indemnity fees are limiting their out-of-hours work.

PMID- 26293454
TI  - Is self-weighing an effective tool for weight loss: a systematic literature
      review and meta-analysis.
AB  - BACKGROUND: There is a need to identify effective behavioural strategies for
      weight loss. Self-weighing may be one such strategy. PURPOSE: To examine the
      effectiveness of self-weighing for weight loss. METHODS: A systematic review and
      meta-analysis of randomised controlled trials that included self-weighing as an
      isolated intervention or as a component within an intervention. We used sub
      groups to analyse differences in frequency of weighing instruction (daily and
      weekly) and also whether including accountability affected weight loss. RESULTS:
      Only one study examined self-weighing as a single strategy and there was no
      evidence it was effective (-0.5 kg 95 % CI -1.3 to 0.3). Four trials added self
      weighing/self-regulation techniques to multi-component programmes and resulted in
      a significant difference of -1.7 kg (95 % CI -2.6 to -0.8). Fifteen trials
      comparing multi-component interventions including self-weighing compared with no
      intervention or minimal control resulted in a significant mean difference of -3.4
      kg (95 % CI -4.2 to -2.6). There was no significant difference in the
      interventions with weekly or daily weighing. In trials which included
      accountability there was significantly greater weight loss (p = 0.03).
      CONCLUSIONS: There is a lack of evidence of whether advising self-weighing
      without other intervention components is effective. Adding self-weighing to a
      behavioural weight loss programme may improve weight loss. Behavioural weight
      loss programmes that include self-weighing are more effective than minimal
      interventions. Accountability may improve the effectiveness of interventions that
      include self-weighing.

PMID- 26293456
TI  - Social distance and anonymity modulate fairness consideration: An ERP study.
AB  - Previous research indicated that fairness consideration can be influenced by
      social distance. However, it is not clear whether social distance and anonymity
      have an interactive impact on fairness evaluation during asset distribution and
      whether these processes can be documented in brain activity. Using a modified
      ultimatum game combined with measures of event related potential (ERP), we
      examined how social distance and anonymity modulate brain response to inequality.
      At the behavior level, we found that acceptance rate and reaction time can be
      substantially modified by social distance and anonymity. Feedback-related
      negativity, an ERP component associated with conflict between cognitive and
      emotion motives, was more negative in response to unfairness than fairness from
      strangers; however, it showed an opposite trend for unfair offers provided by
      friends, suggesting that the influence of social distance on fairness perception
      is relatively fast. The P300 in response to fair offers was more positive when
      the proposers made offers when uncertain about partner identity than when certain
      about partner identity. These results suggest that unfairness is evaluated in a
      fast conflict detection stage and a slower stage that integrates more complex
      social contextual factors such as anonymity. 

PMID- 26293457
TI  - N-acetylglucosaminyltransferase V modulates radiosensitivity and migration of
      small cell lung cancer through epithelial-mesenchymal transition.
AB  - N-acetylglucosaminyltransferase V (Gnt-V) has been linked to the migration of
      various human cancers. Recently we have found that inhibition of Gnt-V increases
      the radiosensitivity of cancer cells. However, the mechanisms by which Gnt-V
      mediates radiosensitivity and migration, especially in small cell lung cancer
      (SCLC) remain unknown. In our study, two SCLC cell lines (H1688 and H146) were
      used to investigate whether Gnt-V modulated the radiosensitivity and migration of
      SCLC cells through the epithelial-mesenchymal transition (EMT). The results
      showed that the expression of Gnt-V correlated with the N stage in patients with
      SCLC. Overexpression of Gnt-V led to a further increase in the relative viable
      cell number and survival fraction with a decrease in apoptosis rate and Bax/Bcl-2
      ratio, when the cells were treated with irradiation. By contrast, knockdown of
      Gnt-V with irradiation resulted in a further decrease in the relative viable cell
      number and survival fraction but an increase in apoptosis rate and Bax/Bcl-2
      ratio. Cells expressing high levels of Gnt-V increased migration whereas low
      levels of Gnt-V suppressed cell migration. Besides, the transient knockdown of
      ZEB2 led to an increase in radiosensitivity and an inhibition in the migration of
      SCLC cells. Furthermore, Gnt-V was negatively correlated with E-cadherin
      expression but positively correlated with N-cadherin, vimentin and ZEB2
      expression. Finally, an in vivo study revealed that upregulation of Gnt-V caused
      tumour growth more quickly, as well as the expression of EMT-related markers (N
      cadherin, vimentin and ZEB2). Taken together, the study suggested that an
      elevation of Gnt-V could lead to the radiosensitivity and migration of SCLC cells
      by inducing EMT, thereby highlighting Gnt-V as a potential therapeutic target for
      the prevention of EMT-associated tumour radioresistance and migration.

PMID- 26293458
TI  - Promoting Health by Addressing Basic Needs: Effect of Problem Resolution on
      Contacting Health Referrals.
AB  - Members of vulnerable populations have heightened needs for health services. One
      advantage of integrating health risk assessment and referrals into social service
      assistance systems such as 2-1-1 is that such systems help callers resolve
      problems in other areas (e.g., housing). Callers to 2-1-1 in Missouri (N= 1,090)
      with at least one behavioral risk factor or cancer screening need were randomly
      assigned to one of three health referral interventions: verbal referrals only,
      verbal referrals + a tailored mailed reminder, or verbal referrals + telephone
      health navigator. After 1 month, we assessed whether the nonhealth problems that
      prompted the 2-1-1 call had been resolved. Logistic regression estimated effects
      of having the problem resolved on calling a health referral. Callers were
      predominantly female (85%) and had a high school education or less (61%); nearly
      half (47%) had incomes under $10,000. The most common service requests were for
      utility assistance (35%), home/family problems (23%), and rent/mortgage
      assistance (12%). At follow-up, 38% of callers reported that all problems
      prompting their 2-1-1 call had been resolved, and 24% reported calling a health
      referral. Resolving all problems prompting the 2-1-1 call was associated with a
      higher odds of contacting a health referral (odds ratio = 1.44, 95% confidence
      interval [1.02, 2.05]) compared to people whose problems were not resolved.
      Multifaceted interventions that help meet non-health-related needs and provide
      support in reaching health-related goals may promote health in vulnerable
      populations. 

PMID- 26293459
TI  - Adolescent (Mis)Perceptions About Nicotine Addiction: Results From a Mixed
      Methods Study.
AB  - PURPOSE: Despite evidence that adolescents become addicted to nicotine even after
      limited use, adolescents believe they can experiment with or smoke cigarettes for
      a few years and easily quit. The goal of this study was to examine adolescents'
      understanding of the definition and process of nicotine addiction using a mixed
      methods approach.Method A total of 367 adolescents with and without smoking
      experience rated the perceived risk for addiction, still being a smoker in 5
      years, and ability to quit smoking. A subsample of adolescents (N= 41) were
      interviewed about their conceptualization and understanding of nicotine
      addiction. Within-participants analyses of variance were conducted to assess
      differences in perceptions of addiction across the three scenarios; thematic
      analyses of interviews were conducted to assess adolescents' understanding of
      addiction.Results Adolescents rated their perceived risk for addiction, still
      being a smoker in 5 years, and ability to quit as significantly different from
      one another for three different scenarios (F= 7.81, 47.78, and 70.27,
      respectively;p< .001). Seven themes describing how youth conceptualize and
      understand addiction emerged from the interview data, including skepticism and
      uncertainty about addiction, how smoking makes a person feel, and family and
      friends' experiences. CONCLUSION: While adolescents have received the message
      that cigarettes are addictive, they are uncertain regarding the definition of
      addiction and have not recognized that addiction means experiencing difficulty
      quitting and continuing to smoke longer than expected. Findings suggest the need
      for comprehensive messaging regarding nicotine addiction in educational,
      clinical, and intervention settings and for product warning messages aimed at
      reducing and preventing tobacco use.

PMID- 26293460
TI  - Concussion Education in U.S. Collegiate Sport: What Is Happening and What Do
      Athletes Want?
AB  - Concussion education for athletes has the potential to play a role in reducing
      the health burden of concussions from sport by modifying individual risk-related
      behaviors. In U.S. collegiate sport, decisions about content and delivery of
      concussion education are left up to the individual institution. This may result
      in a high degree of variability in what educational materials athletes receive
      and is particularly problematic as few concussion education programs have
      demonstrated efficacy. Health educators can play an important role in working
      collaboratively with sports medicine clinicians to design and evaluate evidence
      based concussion education materials for athletes that meet their learning needs.
      As a first step in this process, the present study characterizes the content,
      source, and delivery modalities of concussion currently being provided to U.S.
      collegiate athletes. It also describes the reported concussion education
      preferences of a sample of U.S. collegiate athletes. Participants were 789
      athletic trainers from 276 schools and 325 athletes from four schools. Results
      indicated that education is most frequently provided by athletic trainers but
      that many athletes would also like coaches and physicians to be involved in this
      process. Athletes also indicated a preference for content provision across a
      range of topics, including athletic and academic consequences of continued play
      with a concussion. Implications for the design and delivery of concussion
      education for athletes are discussed. 

PMID- 26293461
TI  - Prediction of Causal Candidate Genes in Coronary Artery Disease Loci.
AB  - OBJECTIVE: Genome-wide association studies have to date identified 159
      significant and suggestive loci for coronary artery disease (CAD). We now report
      comprehensive bioinformatics analyses of sequence variation in these loci to
      predict candidate causal genes. APPROACH AND RESULTS: All annotated genes in the
      loci were evaluated with respect to protein-coding single-nucleotide polymorphism
      and gene expression parameters. The latter included expression quantitative trait
      loci, tissue specificity, and miRNA binding. High priority candidate genes were
      further identified based on literature searches and our experimental data. We
      conclude that the great majority of causal variations affecting CAD risk occur in
      noncoding regions, with 41% affecting gene expression robustly versus 6% leading
      to amino acid changes. Many of these genes differed from the traditionally
      annotated genes, which was usually based on proximity to the lead single
      nucleotide polymorphism. Indeed, we obtained evidence that genetic variants at
      CAD loci affect 98 genes which had not been linked to CAD previously.
      CONCLUSIONS: Our results substantially revise the list of likely candidates for
      CAD and suggest that genome-wide association studies efforts in other diseases
      may benefit from similar bioinformatics analyses.

PMID- 26293464
TI  - An In Vitro Cynomolgus Vascular Surrogate System for Preclinical Drug Assessment
      and Human Translation.
AB  - OBJECTIVES: The predictive value of animal and in vitro systems for drug
      development is limited, particularly for nonhuman primate studies as it is
      difficult to deduce the drug mechanism of action. We describe the development of
      an in vitro cynomolgus macaque vascular system that reflects the in vivo biology
      of healthy, atheroprone, or advanced inflammatory cardiovascular disease
      conditions. APPROACH AND RESULTS: We compare the responses of the in vitro human
      and cynomolgus vascular systems to 4 statins. Although statins exert beneficial
      pleiotropic effects on the human vasculature, the mechanism of action is
      difficult to investigate at the tissue level. Using RNA sequencing, we quantified
      the response to statins and report that most statins significantly increased the
      expression of genes that promote vascular health while suppressing inflammatory
      cytokine gene expression. Applying computational pathway analytics, we identified
      statin-regulated biological themes, independent of cholesterol lowering, that
      provide mechanisms for off-target effects, including thrombosis, cell cycle
      regulation, glycogen metabolism, and ethanol degradation. CONCLUSIONS: The
      cynomolgus vascular system described herein mimics the baseline and inflammatory
      regional biology of the human vasculature, including statin responsiveness, and
      provides mechanistic insight not achievable in vivo.

PMID- 26293463
TI  - Association of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) With
      Cardiovascular Risk in Primary Prevention.
AB  - OBJECTIVE: Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an
      important role in the modulation of low-density lipoprotein metabolism. This
      study was conducted to evaluate the relationship between serum PCSK9
      concentrations and measures of vascular health, subclinical atherosclerosis, and
      adverse cardiovascular events. The relationship between traditional risk factors
      and PCSK9 concentrations was also examined. APPROACH AND RESULTS: The cohort
      consisted of 1527 middle-aged men enrolled in the Firefighters and Their
      Endothelium (FATE) study, who were free of vascular disease and followed up over
      a mean period of 7.2+/-1.7 years. Baseline evaluation included assessment of
      traditional cardiovascular risk factors and measurements of flow-mediated
      dilation, reactive hyperemic velocity time integral, and carotid intima-media
      thickness. Biochemical parameters, including serum PCSK9 concentrations, were
      analyzed to determine predictors of vascular measures and to evaluate the role of
      PCSK9 in the occurrence of adverse cardiovascular events. Multivariate linear
      regression analyses indicated that body mass index, insulin, low-density
      lipoprotein-cholesterol, and triglycerides were independent predictors of PCSK9.
      Further modeling revealed no correlation between PCSK9 concentration and carotid
      intima media thickness, flow-mediated dilation, or reactive hyperemic velocity
      time integral. Analyses indicated no significant association between PCSK9
      concentrations and cardiovascular event occurrences. CONCLUSIONS: Although
      correlated with low-density lipoprotein-cholesterol, insulin, and triglycerides,
      PCSK9 was not associated with measures of vascular function or structure. There
      was also no significant relationship between PCSK9 concentrations and
      cardiovascular events. Thus, although PCSK9 is an important therapeutic target to
      reduce circulating low-density lipoprotein-cholesterol concentrations, it is
      unlikely to be a biomarker of atherosclerotic risk or vascular health.

PMID- 26293462
TI  - Residential Proximity to Major Roadways Is Associated With Increased Levels of
      AC133+ Circulating Angiogenic Cells.
AB  - OBJECTIVES: Previous studies have shown that residential proximity to a roadway
      is associated with increased cardiovascular disease risk. Yet, the nature of this
      association remains unclear, and its effect on individual cardiovascular disease
      risk factors has not been assessed. The objective of this study was to determine
      whether residential proximity to roadways influences systemic inflammation and
      the levels of circulating angiogenic cells. APPROACH AND RESULTS: In a cross
      sectional study, cardiovascular disease risk factors, blood levels of C-reactive
      protein, and 15 antigenically defined circulating angiogenic cell populations
      were measured in participants (n=316) with moderate-to-high cardiovascular
      disease risk. Attributes of roadways surrounding residential locations were
      assessed using geographic information systems. Associations between road
      proximity and cardiovascular indices were analyzed using generalized linear
      models. Close proximity (<50 m) to a major roadway was associated with lower
      income and higher rates of smoking but not C-reactive protein levels. After
      adjustment for potential confounders, the levels of circulating angiogenic cells
      in peripheral blood were significantly elevated in people living in close
      proximity to a major roadway (CD31(+)/AC133(+), AC133(+), CD34(+)/AC133(+), and
      CD34(+)/45(dim)/AC133(+) cells) and positively associated with road segment
      distance (CD31(+)/AC133(+), AC133(+), and CD34(+)/AC133(+) cells), traffic
      intensity (CD31(+)/AC133(+) and AC133(+) cells), and distance-weighted traffic
      intensity (CD31(+)/34(+)/45(+)/AC133(+) cells). CONCLUSIONS: Living close to a
      major roadway is associated with elevated levels of circulating cells positive
      for the early stem marker AC133(+). This may reflect an increased need for
      vascular repair. Levels of these cells in peripheral blood may be a sensitive
      index of cardiovascular injury because of residential proximity to roadways.

PMID- 26293466
TI  - beta3 Integrin Promotes Long-Lasting Activation and Polarization of Vascular
      Endothelial Growth Factor Receptor 2 by Immobilized Ligand.
AB  - OBJECTIVE: During neovessel formation, angiogenic growth factors associate with
      the extracellular matrix. These immobilized factors represent a persistent
      stimulus for the otherwise quiescent endothelial cells (ECs), driving directional
      EC migration and proliferation and leading to new blood vessel growth. Vascular
      endothelial growth factor receptor 2 (VEGFR2) is the main mediator of
      angiogenesis. Although VEGFR2 signaling has been deeply characterized, little is
      known about its subcellular localization during neovessel formation. Aim of this
      study was the characterization and molecular determinants of activated VEGFR2
      localization in ECs during neovessel formation in response to matrix-immobilized
      ligand. APPROACH AND RESULTS: Here we demonstrate that ECs stimulated by
      extracellular matrix-associated gremlin, a noncanonical VEGFR2 ligand, are
      polarized and relocate the receptor in close contact with the angiogenic factor
      enriched matrix both in vitro and in vivo. GM1 (monosialotetrahexosylganglioside)
      positive planar lipid rafts, beta3 integrin receptors, and the intracellular
      signaling transducers focal adhesion kinase and RhoA (Ras homolog gene family,
      member A) cooperate to promote VEGFR2 long-term polarization and activation.
      CONCLUSIONS: A ligand anchored to the extracellular matrix induces VEGFR2
      polarization in ECs. Long-lasting VEGFR2 relocation is closely dependent on lipid
      raft integrity and activation of beta3 integrin pathway. The study of the
      endothelial responses to immobilized growth factors may offer insights into the
      angiogenic process in physiological and pathological conditions, including
      cancer, and for a better engineering of synthetic tissue scaffolds to blend with
      the host vasculature.

PMID- 26293465
TI  - Plasma Levels of Soluble Interleukin-2 Receptor alpha: Associations With Clinical
      Cardiovascular Events and Genome-Wide Association Scan.
AB  - OBJECTIVE: Interleukin (IL) -2 receptor subunit alpha regulates lymphocyte
      activation, which plays an important role in atherosclerosis. Associations
      between soluble IL-2Ralpha (sIL-2Ralpha) and cardiovascular disease (CVD) have
      not been widely studied and little is known about the genetic determinants of sIL
      2Ralpha levels. APPROACH AND RESULTS: We measured baseline levels of sIL-2Ralpha
      in 4408 European American (EA) and 766 African American (AA) adults from the
      Cardiovascular Health Study (CHS) and examined associations with baseline CVD
      risk factors, subclinical CVD, and incident CVD events. We also performed a
      genome-wide association study for sIL-2Ralpha in CHS (2964 EAs and 683 AAs) and
      further combined CHS EA results with those from two other EA cohorts in a meta
      analysis (n=4464 EAs). In age, sex- and race- adjusted models, sIL-2Ralpha was
      positively associated with current smoking, type 2 diabetes mellitus,
      hypertension, insulin, waist circumference, C-reactive protein, IL-6, fibrinogen,
      internal carotid wall thickness, all-cause mortality, CVD mortality, and incident
      CVD, stroke, and heart failure. When adjusted for baseline CVD risk factors and
      subclinical CVD, associations with all-cause mortality, CVD mortality, and heart
      failure remained significant in both EAs and AAs. In the EA genome-wide
      association study analysis, we observed 52 single-nucleotide polymorphisms in the
      chromosome 10p15-14 region, which contains IL2RA, IL15RA, and RMB17, that reached
      genome-wide significance (P<5*10(-8)). The most significant single-nucleotide
      polymorphism was rs7911500 (P=1.31*10(-75)). The EA meta-analysis results were
      highly consistent with CHS-only results. No single-nucleotide polymorphisms
      reached statistical significance in the AAs. CONCLUSIONS: These results support a
      role for sIL-2Ralpha in atherosclerosis and provide evidence for multiple
      associated single-nucleotide polymorphisms at chromosome 10p15-14.

PMID- 26293467
TI  - MicroRNA-15b/16 Attenuates Vascular Neointima Formation by Promoting the
      Contractile Phenotype of Vascular Smooth Muscle Through Targeting YAP.
AB  - OBJECTIVE: To investigate the functional role of the microRNA (miR)-15b/16 in
      vascular smooth muscle (SM) phenotypic modulation. APPROACH AND RESULTS: We found
      that miR-15b/16 is one of the most abundant mRs expressed in contractile vascular
      smooth muscle cells (VSMCs). However, when contractile VSMCs get converted to a
      synthetic phenotype, miR-15b/16 expression is significantly reduced. Knocking
      down endogenous miR-15b/16 in VSMCs attenuates SM-specific gene expression but
      promotes VSMC proliferation and migration. Conversely, overexpression of miR
      15b/16 promotes SM contractile gene expression while attenuating VSMC migration
      and proliferation. Consistent with this, overexpression of miR-15b/16 in a rat
      carotid balloon injury model markedly attenuates injury-induced SM
      dedifferentiation and neointima formation. Mechanistically, we identified the
      potent oncoprotein yes-associated protein (YAP) as a downstream target of miR
      15b/16 in VSMCs. Reporter assays validated that miR-15b/16 targets YAP's 3'
      untranslated region. Moreover, overexpression of miR-15b/16 significantly
      represses YAP expression, whereas conversely, depletion of endogenous miR-15b/16
      results in upregulation of YAP expression. CONCLUSIONS: These results indicate
      that miR-15b/16 plays a critical role in SM phenotypic modulation at least partly
      through targeting YAP. Restoring expression of miR-15b/16 would be a potential
      therapeutic approach for treatment of proliferative vascular diseases.

PMID- 26293468
TI  - Monocyte-Derived Dendritic Cells Upregulate Extracellular Catabolism of
      Aggregated Low-Density Lipoprotein on Maturation, Leading to Foam Cell Formation.
AB  - OBJECTIVE: Although dendritic cells are known to play a role in atherosclerosis,
      few studies have examined the contribution of the wide variety of dendritic cell
      subsets. Accordingly, their roles in atherogenesis remain largely unknown. We
      investigated the ability of different dendritic cell subsets to become foam cells
      after contact with aggregated low-density lipoprotein (LDL; the predominant form
      of LDL found in atherosclerotic plaques). APPROACH AND RESULTS: We demonstrate
      that both murine and human monocyte-derived dendritic cells use exophagy to
      degrade aggregated LDL, leading to foam cell formation, whereas monocyte
      independent dendritic cells are unable to clear LDL aggregates by this mechanism.
      Exophagy is a catabolic process in which objects that cannot be internalized by
      phagocytosis (because of their size or association with extracellular structures)
      are initially digested in an extracellular acidic lytic compartment.
      Surprisingly, we found that monocyte-derived dendritic cells upregulate exophagy
      on maturation. This contrasts various forms of endocytic internalization in
      dendritic cells, which decrease on maturation. Finally, we show that our in vitro
      results are consistent with dendritic cell lipid accumulation in plaques of an
      ApoE(-/-) mouse model of atherosclerosis. CONCLUSIONS: Our results show that
      monocyte-derived dendritic cells use exophagy to degrade aggregated LDL and
      become foam cells, whereas monocyte-independent dendritic cells are unable to
      clear LDL deposits. Furthermore, we find that exophagy is upregulated on
      dendritic cell maturation. Thus, exophagy-mediated foam cell formation in
      monocyte-derived dendritic cells could play a significant role in atherogenesis.

PMID- 26293470
TI  - Earlier switching from intravenous to oral antibiotics owing to electronic
      reminders.
AB  - Paper-based interventions have been shown to stimulate switching from intravenous
      (i.v.) to oral (p.o.) antibiotic therapies. Shorter i.v. durations are associated
      with a lower risk of iatrogenic infections as well as reduced workload and costs.
      The purpose of this study was to determine whether automated electronic reminders
      are able to promote earlier switching. In this controlled before-and-after study,
      an algorithm identified patients who were eligible for i.v.-to-p.o. switch 60 h
      after starting i.v. antimicrobials. Reminders offering guidance on the re
      assessment of initial i.v. therapy were displayed within the electronic health
      records in 12 units during the intervention period (year 2012). In contrast, no
      reminders were visible during the baseline period (2011) and in the control group
      (17 units). A total of 22863 i.v. antibiotic therapies were analysed; 6082
      (26.6%) were switched to p.o. THERAPY: In the intervention group, 757 courses of
      i.v. antibiotics were administered for a mean +/- standard deviation duration of
      5.4 +/- 8.1 days before switching to p.o. antibiotics in the baseline period, and
      794 courses for 4.5 +/- 5.5 days in the intervention period (P = 0.004),
      corresponding to a 17.5% reduction of i.v. administration time. In contrast, in
      the control group the duration increased; 2240 i.v. antibiotics were administered
      for a mean duration of 4.0 +/- 5.9 days in the baseline period, and 2291 for 4.3
      +/- 5.8 days in the intervention period (P = 0.03). Electronic reminders fostered
      earlier i.v.-to-p.o. switches, thereby reducing the duration of initial i.v.
      therapies by nearly a day.

PMID- 26293469
TI  - Post-Transcriptional Regulation of Endothelial Nitric Oxide Synthase Expression
      by Polypyrimidine Tract-Binding Protein 1.
AB  - OBJECTIVE: Endothelial nitric oxide synthase (eNOS) is an important regulator of
      vascular function and its expression is regulated at post-transcriptional levels
      through a yet unknown mechanism. The purpose of this study is to elucidate the
      post-transcriptional factors regulating eNOS expression and function in
      endothelium. APPROACHES AND RESULTS: To elucidate the molecular basis of tumor
      necrosis factor (TNF)-alpha-mediated eNOS mRNA instability, biotinylated eNOS 3'
      untranslational region (UTR) was used to purify its associated proteins by RNA
      affinity chromatography from cytosolic fractions of TNF-alpha-stimulated human
      umbilical vein endothelial cells (HUVECs). We identified 2 cytosolic proteins,
      with molecular weight of 52 and 57 kDa, which specifically bind to eNOS 3'-UTR in
      response to TNF-alpha stimulation. Matrix-assisted laser desorption ionization
      time-of-flight mass spectrometric analysis identified the 57-kDa protein as
      polypyrimidine tract-binding protein 1 (PTB1). RNA gel mobility shift and UV
      cross-linking assays demonstrated that PTB1 binds to a UCUU-rich sequence in eNOS
      3'-UTR, and the C-terminal half of PTB1 is critical to this interaction.
      Importantly, PTB1 overexpression leads to decreased activity of luciferase gene
      fused with eNOS 3'-UTR as well as reduced eNOS expression and activity in human
      ECs. In HUVECs, we show that TNF-alpha markedly increased PTB1 expression,
      whereas adenovirus-mediated PTB1 overexpression decreased eNOS mRNA stability and
      reduced protein expression and endothelium-dependent relaxation. Furthermore,
      knockdown of PTB1 substantially attenuated TNF-alpha-induced destabilization of
      eNOS transcript and downregulation of eNOS expression. CONCLUSIONS: These results
      indicate that PTB1 is essential for regulating eNOS expression at post
      transcriptional levels and suggest a novel therapeutic target for treatment of
      vascular diseases associated with inflammatory endothelial dysfunction.

PMID- 26293471
TI  - Epileptic activity is a surrogate for an underlying etiology and stopping the
      activity has a limited impact on developmental outcome.
AB  - The concept of epileptic encephalopathy is important in clinical practice, but
      its relevance to an individual must be assessed in the appropriate context.
      Except in rare situations, epileptic activity is a surrogate for an underlying
      etiology, and stopping the activity has a limited impact on developmental
      outcome. Labeling a group of epilepsies as "the epileptic encephalopathies,"
      risks minimizing the impact of epileptic activity on cognition and behavior more
      widely in epilepsy. Similarly, describing the encephalopathy associated with many
      infantile onset epilepsies as "epileptic" may be misleading. Finally,
      concentrating on the epileptic activity alone and not considering the wider
      consequences of the underlying etiology on cognitive and behavioral development,
      may focus research efforts and the search for improved therapies on too narrow a
      target. Therefore, epileptic encephalopathies should not be considered as a
      specific group of epilepsies but, rather, the concept of epileptic encephalopathy
      should be applicable to all types of epilepsies and epilepsy syndromes, whenever
      it is relevant in the clinical course of a particular individual, at any age. 

PMID- 26293472
TI  - Investigating nephrotoxicity of polymyxin derivatives by mapping renal
      distribution using mass spectrometry imaging.
AB  - Colistin and polymyxin B are effective treatment options for Gram-negative
      resistant bacteria but are used as last-line therapy due to their dose-limiting
      nephrotoxicity. A critical factor in developing safer polymyxin analogues is
      understanding accumulation of the drugs and their metabolites, which is currently
      limited due to the lack of effective techniques for analysis of these challenging
      molecules. Mass spectrometry imaging (MSI) allows direct detection of targets
      (drugs, metabolites, and endogenous compounds) from tissue sections. The
      presented study exemplifies the utility of MSI by measuring the distribution of
      polymyxin B1, colistin, and polymyxin B nonapeptide (PMBN) within dosed rat
      kidney tissue sections. The label-free MSI analysis revealed that the nephrotoxic
      compounds (polymyxin B1 and colistin) preferentially accumulated in the renal
      cortical region. The less nephrotoxic analogue, polymyxin B nonapeptide, was more
      uniformly distributed throughout the kidney. In addition, metabolites of the
      dosed compounds were detected by MSI. Kidney homogenates were analyzed using
      LC/MS/MS to determine total drug exposure and for metabolite identification. To
      our knowledge, this is the first time such techniques have been utilized to
      measure the distribution of polymyxin drugs and their metabolites. By
      simultaneously detecting the distribution of drug and drug metabolites, MSI
      offers a powerful alternative to tissue homogenization analysis and label or
      antibody-based imaging. 

PMID- 26293473
TI  - Spontaneous regression of intracranial aneurysm following remote ruptured
      aneurysm treatment with pipeline stent assisted coiling.
AB  - Spontaneous aneurysm regression is a rare phenomenon. We present the interesting
      case of a 54-year-old woman who was admitted with a Hunt/Hess grade IV, Fisher
      grade III subarachnoid hemorrhage and multiple intracranial aneurysms. She was
      treated with coiling of the largest paraclinoid aneurysm and placement of a flow
      diverting pipeline embolization device that covered all internal carotid artery
      (ICA) aneurysms. A follow-up angiogram at 6 months showed remodeling of the ICA
      with complete obliteration of all treated aneurysms. A distant, untreated, right
      frontal M2 aneurysm regressed spontaneously, after the flow was diverted away
      from it with the stent. The literature is reviewed, and potential
      pathophysiological mechanisms leading to aneurysm regression are discussed. 

PMID- 26293474
TI  - Isolation of Genetically Tractable Most-Wanted Bacteria by Metaparental Mating.
AB  - Metagenomics has rapidly advanced our inventory and appreciation of the genetic
      potential inherent to the gut microbiome. However it is widely accepted that two
      key constraints to further genetic dissection of the gut microbiota and host
      microbe interactions have been our inability to recover new isolates from the
      human gut, and the paucity of genetically tractable gut microbes. To address this
      challenge we developed a modular RP4 mobilisable recombinant vector system and an
      approach termed metaparental mating to support the rapid and directed isolation
      of genetically tractable fastidious gut bacteria. Using this approach we isolated
      transconjugants affiliated with Clostridium cluster IV (Faecalibacterium and
      Oscillibacter spp.), Clostridium cluster XI (Anaerococcus) and Clostridium XIVa
      (Blautia spp.) and group 2 ruminococci amongst others, and demonstrated that the
      recombinant vectors were stably maintained in their recipient hosts. By a similar
      approach we constructed fluorescently labelled bacterial transconjugants
      affiliated with Clostridium cluster IV (including Flavonifractor and
      Pseudoflavonifractor spp.), Clostridium XIVa (Blautia spp.) and Clostridium
      cluster XVIII (Clostridium ramosum) that expressed a flavin mononucleotide-based
      reporter gene (evoglow-C-Bs2). Our approach will advance the integration of
      bacterial genetics with metagenomics and realize new directions to support a more
      mechanistic dissection of host-microbe associations relevant to human health and
      disease. 

PMID- 26293475
TI  - N6-methyladenine functions as a potential epigenetic mark in eukaryotes.
AB  - N(6)-methyladenine (6mA) is one of the most abundant types of DNA methylation,
      and plays an important role in bacteria; however, its roles in higher eukaryotes,
      such as plants, insects, and mammals, have been considered less important. Recent
      studies highlight that 6mA does indeed occur, and that it plays an important role
      in eukaryotes, such as worm, fly, and green algae, and thus the regulation of 6mA
      has emerged as a novel epigenetic mechanism in higher eukaryotes. Despite this
      intriguing development, a number of important issues regarding its biological
      roles are yet to be addressed. In this review, we focus on the 5mC and 6mA
      modifications in terms of their production, distribution, and the erasure of 6mA
      in higher eukaryotes including mammals. We perform an analysis of the potential
      functions of 6mA, hence widening understanding of this new epigenetic mark in
      higher eukaryotes, and suggesting future studies in this field.

PMID- 26293476
TI  - Design of inhibitors of BCRP/ABCG2.
AB  - BCRP/ABCG2, a second member of ABC transporter subclass G, has been shown to be
      overexpressed in several solid tumors, acute myelogenous leukemia and chronic
      myeloid leukemia. A variety of chemically unrelated anticancer drugs have been
      found to be transported by ABCG2 leading to their lower intracellular
      accumulation and hence causing chemoresistance. Until now several efforts have
      been taken to identify potent and selective inhibitors of ABCG2. Recent studies
      carried out to deign BCRP inhibitors have been able to point out the effect of
      the substitution pattern in compound scaffolds on the potency, selectivity and
      cytotoxicity of ABCG2 inhibitors. 

PMID- 26293477
TI  - Rapid Particle Patterning in Surface Deposited Micro-Droplets of Low Ionic
      Content via Low-Voltage Electrochemistry and Electrokinetics.
AB  - Electrokinetic phenomena are a powerful tool used in various scientific and
      technological applications for the manipulation of aqueous solutions and the
      chemical entities within them. However, the use of DC-induced electrokinetics in
      miniaturized devices is highly limited. This is mainly due to unavoidable
      electrochemical reactions at the electrodes, which hinder successful
      manipulation. Here we present experimental evidence that on-chip DC manipulation
      of particles between closely positioned electrodes inside micro-droplets can be
      successfully achieved, and at low voltages. We show that such manipulation, which
      is considered practically impossible, can be used to rapidly concentrate and
      pattern particles in 2D shapes in inter-electrode locations. We show that this is
      made possible in low ion content dispersions, which enable low-voltage
      electrokinetics and an anomalous bubble-free water electrolysis. This phenomenon
      can serve as a powerful tool in both microflow devices and digital microfluidics
      for rapid pre-concentration and particle patterning. 

PMID- 26293478
TI  - Knowledge, attitudes and practices on Rift Valley fever among agro pastoral
      communities in Kongwa and Kilombero districts, Tanzania.
AB  - BACKGROUND: Rift valley fever (RVF) is a re-emerging viral vector-borne disease
      with rapid global socio-economic impact. A large RVF outbreak occurred in
      Tanzania in 2007 and affected more than half of the regions with high (47 %) case
      fatality rate. Little is known about RVF and its dynamics. A cross sectional
      study was conducted to assess the knowledge, attitudes and practices regarding
      RVF in Kongwa and Kilombero districts, Tanzania. METHODS: We conducted a cross
      sectional survey among a randomly selected sample of individuals in 2011. We
      administered questionnaires to collect data on demographic characteristics,
      knowledge on symptoms, mode of transmission, prevention, attitudes and health
      seeking practices. RESULTS: A total of 463 community members participated in this
      study. The mean (+/-SD) age was 39.8 +/- 14.4 years and 238 (51.4 %) were female.
      Majority of respondents had heard of RVF. However, only 8.8 % knew that
      mosquitoes were transmitting vectors. Male respondents were more likely to have
      greater knowledge about RVF. A small proportion mentioned clinical signs and
      symptoms of RVF in animals while 73.7 % mentioned unhealthy practices related to
      handling and consumption of dead animals. Thorough boiling of milk and cooking of
      meat were commonly mentioned as preventive measures for RVF. Majority (74.6 %)
      sought care for febrile illness at health facilities. Few (24.3 %) reported the
      use of protective gears to handle dead/sick animal while 15.5 % were consuming
      dead animals. CONCLUSION: Our study highlights the need to address the limited
      knowledge about RVF and promoting appropriate and timely health seeking
      practices. Rift valley fever outbreaks can be effectively managed with
      collaborative efforts of lay and professional communities with a shared
      perception that it poses a serious threat to public and animal health. The fact
      that this study was conducted in "high risk transmission areas" warrants further
      inquiry in other geographic regions with relatively low risk of RVF.

PMID- 26293479
TI  - Transition metal-catalyzed allylic substitution reactions with unactivated
      allylic substrates.
AB  - The transition metal-catalyzed allylic substitution of unactivated allylic
      substrates (allylic alcohols, allylic ethers and allylic amines) is rapidly
      becoming an important area of research. There are several advantages to using
      these substrates in allylic substitution reactions: the use of unactivated
      alcohols minimizes the production of waste by-products and reaction steps; and
      allylic ethers and allylic amines are useful substrates because of their
      stability and their presence in numerous biologically active compounds. Research
      in this field has therefore gained widespread attention for promoting the
      development of efficient and environmentally benign procedures for the formation
      of C-C, C-N and C-O bonds. 

PMID- 26293480
TI  - Pyrene Based Chemosensor for Selective Sensing of Fluoride in Aprotic and Protic
      Environment.
AB  - A new aromatic hydrazone based on pyrene-1-aldehyde was synthesized and
      characterized by (1)H NMR and mass spectrometric analyses. The sensing properties
      of the hydrazone were studied by absorption and fluorescence studies in the
      aprotic solvent DMSO. It was capable of visual and fluorescent detection of
      fluoride over competitive ions (Cl(-), Br(-), H2PO4 (-), AcO(-)). Moreover, the
      in-situ prepared iron(III) complex of the hydrazone was investigated as a turn
      off fluorescent fluoride sensor in aqueous medium by displacement mechanism. 

PMID- 26293481
TI  - Homeostatic effect of p-chloro-diphenyl diselenide on glucose metabolism and
      mitochondrial function alterations induced by monosodium glutamate administration
      to rats.
AB  - The metabolic syndrome is a group of metabolic alterations considered a worldwide
      public health problem. Organic selenium compounds have been reported to have many
      different pharmacological actions, such as anti-hypercholesterolemic and anti
      hyperglycemic. The aim of this study was to evaluate the effect of p-chloro
      diphenyl diselenide (p-ClPhSe)2, an organic selenium compound, in a model of
      obesity induced by monosodium glutamate (MSG) administration in rats. The rats
      were treated during the first ten postnatal days with MSG and received (p
      ClPhSe)2 (10 mg/kg, intragastrically) from 45th to 51 th postnatal day. Glucose,
      lipid and lactate levels were determined in plasma of rats. Glycogen levels and
      activities of tyrosine aminotransferase, hexokinase, citrate synthase and glucose
      6-phosphatase (G-6-Pase) were determined in livers of rats. Renal G-6-Pase
      activity was also determined. The purine content [Adenosine triphosphate (ATP),
      adenosine diphosphate (ADP) and adenosine monophosphate] and mitochondrial
      functionality in the liver were also investigated. p-(ClPhSe)2 did not alter the
      reduction in growth performance and in the body weight caused by MSG but reduced
      epididymal fat deposition of rats. p-(ClPhSe)2 restored glycemia, triglycerides,
      cholesterol and lactate levels as well as the glucose metabolism altered in rats
      treated with MSG. p-(ClPhSe)2 restored hepatic mitochondrial dysfunction and the
      decrease in citrate synthase activity and ATP and ADP levels caused by MSG in
      rats. In summary, (p-ClPhSe)2 had homeostatic effects on glucose metabolism and
      mitochondrial function alterations induced by MSG administration to rats.

PMID- 26293482
TI  - A Phenotypic Analysis of Regulatory T Cells and Uterine NK Cells from First
      Trimester Pregnancies and Associations with HLA-G.
AB  - PROBLEM: The prevalence of regulatory T cells and NK cells expressing activation
      and HLA-G receptors, and the influence of in vivo sHLA-G and mHLAG on HLA-G
      receptors expressed by NK cells in the uterine compartment is unclear. METHOD OF
      STUDY: KIR2DL4 and/or ILT2 expression on regulatory T cells and NK cells from the
      placental bed and peripheral blood in first trimester was assessed using flow
      cytometry. Expression of mHLA-G on trophoblast cells and sHLA-G in 'uterine' and
      peripheral blood was determined with ELISA and flow cytometry, and specific
      associations with expression levels of cognate receptors or activation markers on
      immune cells were determined. RESULTS: In the placental bed, CD45RA surface
      expression on Tregs was similar to peripheral Tregs in pregnant women, but T
      cells with lower CD4 and CD8 expression were accumulated. HLA-G receptor
      expression was increased on NK cells from 'uterine blood'. Soluble HLA-G was
      significantly increased in 'uterine blood' compared with peripheral blood, but no
      correlation was found between sHLA-G and mHLA-G in the uterine compartment. A
      correlation was found between sHLA-G and the fraction of KIR2DL4-positive NK
      cells in the uterine compartment, and a tendency was observed between mHLA-G and
      the fraction of ILT2-positive NK cells in the uterine compartment. CONCLUSION:
      The NK subset in the placental bed displays a unique phenotype that may be
      influenced by mHLA-G on trophoblast cells and locally accumulated sHLA-G in the
      uterus.

PMID- 26293483
TI  - Selective Catalytic Hydrogenation of Heteroarenes with N-Graphene-Modified Cobalt
      Nanoparticles (Co3O4-Co/NGr@alpha-Al2O3).
AB  - Cobalt oxide/cobalt-based nanoparticles featuring a core-shell structure and
      nitrogen-doped graphene layers on alumina are obtained by pyrolysis of
      Co(OAc)2/phenanthroline. The resulting core-shell material (Co3O4-Co/NGr@alpha
      Al2O3) was successfully applied in the catalytic hydrogenation of a variety of N
      heteroarenes including quinolines, acridines, benzo[h], and 1,5-naphthyridine as
      well as unprotected indoles. The peculiar structure of the novel heterogeneous
      catalyst enables activation of molecular hydrogen at comparably low temperature.
      Both high activity and selectivity were achieved in these hydrogenation
      processes, to give important building blocks for bioactive compounds as well as
      the pharmaceutical industry. 

PMID- 26293484
TI  - Computational Modeling of Neuronal Current MRI Signals with Rat Somatosensory
      Cortical Neurons.
AB  - Magnetic field generated by active neurons has recently been considered to
      determine location of neuronal activity directly with magnetic resonance imaging
      (MRI), but controversial results have been reported about detection of such small
      magnetic fields. In this study, multiple neuronal morphologies of rat tissue were
      modeled to investigate better estimation of MRI signal change produced by
      neuronal magnetic field (NMF). Ten pyramidal neurons from layer II to VI of rat
      somatosensory area with realistic morphology, biophysics, and neuronal density
      were modeled to simulate NMF of neuronal tissue, from which effects of NMF on MRI
      signals were obtained. Neuronal current MRI signals, which consist of relative
      magnitude signal change (RMSC) and phase signal change (PSC), were at least three
      and one orders of magnitude less than a tissue with single neuron type,
      respectively. Also, a reduction in voxel size could increase signal alterations.
      Furthermore, with selection of zenith angle of external main magnetic field
      related to tissue surface near to 90 degrees , RMSC could be maximized. This
      value for PSC would be 90 degrees  for small voxel size and zero degree for large
      ones. 

PMID- 26293485
TI  - MetaObtainer: A Tool for Obtaining Specified Species from Metagenomic Reads of
      Next-generation Sequencing.
AB  - Reads classification is an important fundamental problem in metagenomics study.
      With the development of next-generation sequencing, metagenome samples can be
      generated using much less money and time. However, the short reads generated by
      next-generation sequencing make the problem of reads classification much more
      difficult than before. None of the existing tools can assign NGS short reads to
      each genome accurately, which limit their use in real application. Fortunately,
      in many applications, it is meaningless to separate all the species in the
      metagenome sample from each other. That is because we usually only focus on some
      specified species categories in the sample and do not care about the others.
      There is no existing tool that is designed technically for obtaining specified
      species from short metagenome reads generated by next-generation sequencing. In
      this paper, we propose a tool named MetaObtainer to obtain the specified species
      from next-generation sequencing short reads. The tool synthesizes some of newest
      technologies for processing of short reads, so it can have better performance
      than other tools. It can (1) deal with next-generation sequencing reads which are
      shorter than 100 bp with very high accuracy (both of precision and recall are
      more than 90%); (2) find unknown species using the reference genomes of species
      which are similar with it; (3) perform well when reads of specified species are
      very few in the dataset; (4) handle genomes of similar abundance levels as well
      as different abundance levels (1:10); and (5) obtain multiple species categories
      from metagenome sample.

PMID- 26293486
TI  - [Pilon fractures].
AB  - Pilon fractures are articular fractures of the distal tibia which involve the
      weight bearing part of the ankle joint. Assessment of the fracture is carried out
      with computed tomography and evaluation of the skin and soft tissue damage. In
      joint-preserving surgical reconstruction, treatment of the soft tissue damage has
      priority. The surgical approaches are preferably local and when necessary
      multiple (up to three) and performed simultaneously but the localization also
      depends on the trauma-induced damage. The surgical strategy includes joint
      distraction, sequential joint reconstruction and joint axis correction as well as
      early non-weight bearing joint mobilization. 

PMID- 26293488
TI  - Tracing temperature in a nanometer size region in a picosecond time period.
AB  - Irradiation of materials with either swift heavy ions or slow highly charged ions
      leads to ultrafast heating on a timescale of several picosecond in a region of
      several nanometer. This ultrafast local heating result in formation of
      nanostructures, which provide a number of potential applications in
      nanotechnologies. These nanostructures are believed to be formed when the local
      temperature rises beyond the melting or boiling point of the material.
      Conventional techniques, however, are not applicable to measure temperature in
      such a localized region in a short time period. Here, we propose a novel method
      for tracing temperature in a nanometer region in a picosecond time period by
      utilizing desorption of gold nanoparticles around the ion impact position. The
      feasibility is examined by comparing with the temperature evolution predicted by
      a theoretical model. 

PMID- 26293487
TI  - Antimicrobial activities of actinomycetes isolated from unexplored regions of
      Sundarbans mangrove ecosystem.
AB  - BACKGROUND: New broad spectrum antimicrobial agents are urgently needed to combat
      frequently emerging multi drug resistant pathogens. Actinomycetes, the most
      talented group of microorganisms isolated from unexplored regions of the world
      may be the ultimate solution to this problem. Thus the aim of this study was to
      isolate several bioactive actinomycetes strains capable of producing
      antimicrobial secondary metabolite from Sundarbans, the only mangrove tiger land
      of the world. RESULTS: Fifty four actinomycetes were isolated and analyzed for
      antimicrobial activity against fifteen test organisms including three
      phytopathogens. Nine morphologically distinct and biologically active isolates
      were subjected to polyphasic identification study.16 s rDNA sequencing indicated
      eight isolates to reveal maximum similarity to the genus streptomyces, whereas
      one isolate presented only 93.57% similarity with Streptomyces albogriseolus NRRL
      B-1305(T). Seventy-one carbon sources and twenty-three chemical sources
      utilization assay revealed their metabolic relatedness. Among these nine isolates
      three specific strains were found to have notably higher degree of antimicrobial
      potential effective in a broader range including phyto-pathogenic fungus. Finally
      the strain SMS_SU21, which showed antimicrobial activity with MIC value of 0.05
      mg ml(-1) and antioxidant activity with IC50 value of 0.242 +/- 0.33 mg ml(-1)
      was detected to be the most potential one. True prospective of this strain was
      evaluated utilizing GC-MS and the bioactive compound responsible for
      antimicrobial activity was purified. CONCLUSION: Rare bioactive actinomycetes
      were isolated from unexplored heritage site. Antimicrobial compound has also been
      identified and purified which is active against a broad range of pathogens.

PMID- 26293489
TI  - Correlation Between Daam2 Expression Changes and Demyelination in Guillain-Barre
      Syndrome.
AB  - Wnt signaling has been implicated in developmental and regenerative myelination
      of the CNS and PNS. The present translational investigation was undertaken to
      assess whether a soluble factor like Wnt may be responsible for the critically
      important skeletal muscle neuromuscular junction-Schwann cell communication.
      Specifically, three key aspects were examined: (a) whether the expression of
      Daam2, disheveled-associated activator of morphogenesis, a key Wnt signaling
      downstream effector, and PIP5K is changed in the demyelinating conditions and
      under different stages of progress of clinical recovery of patients with Guillain
      Barre syndrome; (b) whether critical protein interactions of Daam2 with
      disheveled and Arf6 are changed; and (c) whether expression of c-Jun/Krox, a key
      negative regulator of remyelination, is changed. Daam2 was elevated in acute
      presentation in GB syndrome. Reduction occurred with clinical improvement of the
      patients. With progressive clinical improvement, c-Jun/Krox expression
      significantly reduced with time. Wnt signaling likely causes immediate early gene
      activation and transcriptional shutdown of factors critical for formation and
      maintenance of myelination. Whether the findings of the present study are
      specific to pathophysiology of demyelination in acute infectious
      polyradiculopathy and multiple sclerosis or a generalized aspect of demyelinating
      diseases merits to be examined in future studies. 

PMID- 26293491
TI  - One-Pot Fabrication of Dendritic NiO@carbon-nitrogen Dot Electrodes for Screening
      Blood Glucose Level in Diabetes.
AB  - Selective and sensitive glucose sensors with fast response for screening diabetic
      blood level are demanded. In this paper, the one-pot nanoarchitecture of
      dendritic NiO@carbon-nitrogen (C-N) dots (designated as NCD) sphere-wrapping Ni
      foam electrodes are reported as an effective and sensitive glucose sensor in
      blood samples. In this construction design, the NCD sphere electrode with
      excessive surface defects, large fractions of catalytic active sites, high
      surface area, and mobility of electron transfer through the actively surface NCD
      sphere can massively enhance the electrocatalytic activity for nonenzymatic
      glucose detection in diabetic blood. This portable sensor enables highly
      sensitive recognition of glucose detection (~0.01 * 10-6 m) over a wider linear
      range (~0.005-12 * 10-3 m) with rapid response time of a few seconds. The key
      result is that the engineered NCD sphere electrodes function as simple, easy-to
      use electrochemical sensing assays of glucose levels in diabetic blood patients
      with a wide range of precision or linearity, recyclability, and excellent
      selectivity, even in the presence of potentially interfering organic (ascorbic
      acid, uric acid, dopamine, lactose, maltose, and sucrose) and inorganic (NaCl,
      Na2 SO4 , KCl, and K2 SO4 ) species. The results demonstrate the potential for
      the electrochemical sensors to be used in preventing serious health problems
      associated with diabetes mismanagement.

PMID- 26293490
TI  - Association between inhaler use and risk of haemoptysis in patients with non
      cystic fibrosis bronchiectasis.
AB  - BACKGROUND AND OBJECTIVE: Inhaled medications have been widely applied to
      patients with airflow limiting non-cystic fibrosis (non-CF) bronchiectasis.
      However, the association between the use of inhalers and the development of
      haemoptysis has rarely been explored. The objective of this study was to assess
      the association between the risk of haemoptysis and the use of inhalers in
      patients with non-CF bronchiectasis. METHODS: A nested case-control study was
      performed using a national claims database from 1 January 2009 to 31 December
      2011. Inhalers including inhaled corticosteroids (ICS), long-acting beta2
      agonists (LABA), long-acting muscarinic antagonists (LAMA), short-acting beta2
      agonists (SABA), short-acting muscarinic antagonists (SAMA) and their
      combinations were tested for the risk of clinically significant haemoptysis
      events. RESULTS: Among the 62 530 eligible new users of inhalers with non-CF
      bronchiectasis, 6180 patients with haemoptysis and 27 486 strictly matched
      controls were selected. In the unadjusted analyses, SAMA, LAMA, SABA and ICS/LABA
      significantly increased the risk of haemoptysis. After adjustment for other
      inhaled respiratory medications, comorbidities, health-care utilization and
      concomitant medications, SAMA, SABA and LAMA consistently increased the risk of
      haemoptysis (SAMA: odds ratio (OR), 1.6; 95% confidence interval (CI), 1.1-1.4;
      LAMA: OR, 1.2; 95% CI: 1.1-1.2; SABA: OR, 1.2; 95% CI: 1.1-1.2). The association
      between anticholinergics (SAMA and LAMA) and risk of haemoptysis showed a dose
      dependent trend (P for trend, <0.001). CONCLUSIONS: The use of SABA and inhaled
      anticholinergics in patients with non-CF bronchiectasis increased the risk of
      haemoptysis. The risk-benefit ratio of inhaled bronchodilators should be
      considered in the haemoptysis-susceptible population.

PMID- 26293492
TI  - Furfuralcohol Co-Polymerized Urea Formaldehyde Resin-derived N-Doped Microporous
      Carbon for CO2 Capture.
AB  - Carbon-based adsorbent is considered to be one of the most promising adsorbents
      for CO2 capture form flue gases. In this study, a series of N-doped microporous
      carbon materials were synthesized from low cost and widely available urea
      formaldehyde resin co-polymerized with furfuralcohol. These N-doped microporous
      carbons showed tunable surface area in the range of 416-2273 m(2) g(-1) with
      narrow pore size distribution within less than 1 nm and a high density of the
      basic N functional groups (2.93-13.92 %). Compared with the carbon obtained from
      urea resin, the addition of furfuralcohol apparently changed the surface chemical
      composition and pore size distribution, especially ultramicropores as can be
      deduced from the X-ray photoelectron spectroscopy (XPS), Fourier transform
      infrared (FT-IR), and pore size distribution measurements and led to remarkable
      improvement on CO2 adsorption capacity. At 1 atm, N-doped carbons activated at
      600  degrees C with KOH/UFFC weight ratio of 2 (UFFA-2-600) showed the highest
      CO2 uptake of 3.76 and 1.57 mmol g(-1) at 25 and 75  degrees C, respectively. 

PMID- 26293493
TI  - Realization of Dirac Cones in Few Bilayer Sb(111) Films by Surface Modification.
AB  - We report the first-principle study on the recovery and linearization of Dirac
      cones in the electronic band structures of a few bilayer Sb(111) films (n-BL Sb)
      by surface modification. Due to the interaction between the surface states on the
      two surfaces of a free-standing film, the distorted Dirac cone in n-BL Sb(111) (n
      < 5) disappears. We demonstrate that the Dirac cone can be restored by
      functionalizing one surface with certain atoms including H, Ag, and Au, to reduce
      the inter-surface interaction. We further show that an ideal Dirac cone with
      linear dispersion of topological surface states near the zone center can be
      realized by functionalizing both surfaces of the film with oxygen, which enhances
      spin-orbital coupling. The realization of Dirac cone by surface functionalization
      shows promise for applications of topologic materials to spintronic devices and
      their operation in complicated conditions. 

PMID- 26293494
TI  - Solution-Processed Cu2ZnSn(S,Se) 4 Thin-Film Solar Cells Using Elemental Cu, Zn,
      Sn, S, and Se Powders as Source.
AB  - Solution-processed approach for the deposition of Cu2ZnSn (S,Se)4 (CZTSSe)
      absorbing layer offers a route for fabricating thin film solar cell that is
      appealing because of simplified and low-cost manufacturing, large-area coverage,
      and better compatibility with flexible substrates. In this work, we present a
      simple solution-based approach for simultaneously dissolving the low-cost
      elemental Cu, Zn, Sn, S, and Se powder, forming a homogeneous CZTSSe precursor
      solution in a short time. Dense and compact kesterite CZTSSe thin film with high
      crystallinity and uniform composition was obtained by selenizing the low
      temperature annealed spin-coated precursor film. Standard CZTSSe thin film solar
      cell based on the selenized CZTSSe thin film was fabricated and an efficiency of
      6.4 % was achieved. 

PMID- 26293495
TI  - The Antibacterial Activity of Ta-doped ZnO Nanoparticles.
AB  - A novel photocatalyst of Ta-doped ZnO nanoparticles was prepared by a modified
      Pechini-type method. The antimicrobial study of Ta-doped ZnO nanoparticles on
      several bacteria of Gram-positive Bacillus subtilis (B. subtilis) and
      Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli)
      and Pseudomonas aeruginosa (P. aeruginosa) were performed using a standard
      microbial method. The Ta-doping concentration effect on the minimum inhibitory
      concentration (MIC) of various bacteria under dark ambient has been evaluated.
      The photocatalytical inactivation of Ta-doped ZnO nanoparticles under visible
      light irradiation was examined. The MIC results indicate that the incorporation
      of Ta(5+) ions into ZnO significantly improve the bacteriostasis effect of ZnO
      nanoparticles on E. coli, S. aureus, and B. subtilis in the absence of light.
      Compared to MIC results without light irradiation, Ta-doped ZnO and pure ZnO
      nanoparticles show much stronger bactericidal efficacy on P. aeruginosa, E. coli,
      and S. aureus under visible light illumination. The possible antimicrobial
      mechanisms in Ta-doped ZnO systems under visible light and dark conditions were
      also proposed. Ta-doped ZnO nanoparticles exhibit more effective bactericidal
      efficacy than pure ZnO in dark ambient, which can be attributed to the
      synergistic effect of enhanced surface bioactivity and increased electrostatic
      force due to the incorporation of Ta(5+) ions into ZnO. Based on the
      antibacterial tests, 5 % Ta-doped ZnO is a more effective antimicrobial agent
      than pure ZnO. 

PMID- 26293496
TI  - Dynamics of Optically-Generated Carriers in Si (100) and Si (111) Substrate-Grown
      GaAs/AlGaAs Core-Shell Nanowires.
AB  - GaAs/Al0.1Ga0.9As core-shell nanowires (CSNWs), with average lateral size of 125
      nm, were grown on gold nanoparticle-activated Si (100) and Si (111) substrates
      via molecular beam epitaxy. Room temperature-photoluminescence (RT-PL) from the
      samples showed bulk-like GaAs and Al0.1Ga0.9As bandgap emission peaks at 1.43 and
      1.56 eV, respectively. Higher PL emission intensity of the sample on Si (111)
      compared to that on Si (100) is attributed to uniform Al0.1Ga0.9As shell
      passivation of surface states on Si (111)-grown CSNWs. Carrier dynamics in two
      different temporal regimes were studied. In the sub-nanosecond time scale (300
      500 ps), time-resolved radiative recombination efficiency of carriers was
      examined. In the 0-4 ps range, surface field-driven ballistic transport of
      carriers was probed in terms of the radiated terahertz (THz) waves. Time-resolved
      PL measurements at 300 K revealed that the carrier recombination lifetime of the
      GaAs core on Si (100)-grown CSNWs is 333 ps while that on Si (111)-grown sample
      is 500 ps. Ultrafast photoexcitation of GaAs core on the two samples generated a
      negligible difference in the intensity and bandwidth of emitted THz radiation.
      This result is ascribed to the fact that the deposited GaAs material on both
      substrates produced samples with comparable NW densities and similar GaAs core
      average diameter of about 75 nm. The samples' difference in GaAs core's carrier
      recombination lifetime did not influence THz emission since the two processes
      involve distinct mechanisms. The THz spectrum of CSNWs grown on Si (111)
      exhibited Fabry-Perot modes that originated from multiple reflections of THz
      waves within the Si substrate. 

PMID- 26293497
TI  - Characteristic changes of saliva and taste in burning mouth syndrome patients.
AB  - BACKGROUND: Burning mouth syndrome (BMS) is characterized by chronic pain with a
      burning sensation of the tongue and oral mucosa and reported to be often
      accompanied by subjective xerostomia and dysgeusia. Since the etiology of BMS has
      not been elucidated, to understand the characteristics of BMS, we measured some
      components of saliva and taste sensitivity and compared the measured values
      between BMS and healthy subjects. METHODS: Unstimulated saliva was collected from
      15 female BMS patients and 30 healthy women. The flow rate, viscosity
      (spinnability) and concentration of secretory IgA (SIgA) of saliva and serum
      antioxidant capacity were measured. The recognition thresholds for sweet, salty,
      sour, bitter, and umami tastes were measured by whole-mouth method. The
      statistical analyses were performed using Student's t-test, and P < 0.05 was
      considered to be significant. RESULTS: In BMS group, the flow rate of saliva was
      significantly lower and the spinnability was significantly higher compared with
      healthy group. The secreted amount of SIgA per min and serum antioxidant capacity
      was significantly lower in the patients. The threshold for sourness in patients
      was significantly higher, while those for other tastes did not differ from
      healthy group. CONCLUSIONS: BMS patients showed lower salivary flow and higher
      salivary spinnability. These results together with decreased SIgA amount, suggest
      that BMS may be relevant to the deterioration of salivary condition, which could
      in turn affect taste function. Furthermore, the lower antioxidant capacity in
      patient's serum suggests that it can serve as a diagnostic tool for BMS.

PMID- 26293498
TI  - Bronchiectasis in Germany: a population-based estimation of disease prevalence.

PMID- 26293499
TI  - Maternal body mass index, neonatal lung function and respiratory symptoms in
      childhood.
AB  - Recent studies have shown that maternal obesity is associated with increased risk
      of wheezing in the offspring. We assessed whether impaired neonatal lung function
      could explain this association. We measured neonatal lung function in 2606
      children of our prospective birth cohort. Information about daily symptoms of
      wheezing was obtained using questionnaires. Consultations and prescriptions for
      wheezing illnesses were derived from general practitioner patient files. Higher
      maternal body mass index (BMI) was associated with increased risk of wheezing in
      the first year of life and more consultations and prescriptions for wheezing
      illnesses until the age of 5 years. Lung function could partially explain the
      association with wheezing in the first year of life. Adding respiratory
      resistance to the model decreased the incidence rate ratio from 1.023 (95% CI
      1.008-1.039) to 1.015 (95% CI 0.998-1.032). Anthropometrics of the 5-year-olds
      largely explained the association with consultations. Intermediates or
      confounders could not explain the association with prescriptions. There is an
      association between higher maternal BMI and increased risk of wheezing illnesses.
      In the first year of life, it is largely explained by an impaired lung function
      in early life, especially in children of nonatopic mothers. At the age of 5
      years, infant lung function is of minor influence in this association.

PMID- 26293500
TI  - Poor standardisation of plethysmographic specific airways resistance measurement
      despite widespread use.

PMID- 26293501
TI  - Infant respiratory infections and later respiratory hospitalisation in childhood.
AB  - Acute respiratory infections (ARI) cause significant morbidity in infancy. We
      sought to quantify the relationship between ARI and development of respiratory
      morbidity in early childhood. Population-based longitudinal hospitalisation data
      were linked to perinatal, birth and death records for 145,580 Western Australian
      children from 1997 to 2002. We conducted Cox regression with sensitivity analyses
      to quantify the risk of recurrent ARI in infancy for respiratory hospitalisation
      after the age of 3 years. ARI in infancy was significantly related to respiratory
      hospitalisation before (hazard ratio (HR) 3.5, 95% CI 3.1-3.8) and after (HR 3.0,
      95% CI 2.6-3.4) adjusting for known risk factors including maternal smoking
      during pregnancy, season of birth, delivery mode and gestational age. We noted a
      dose response with the number and length of infant ARI hospitalisations and
      increasing risk with no effect modification by gestational age. Results were
      similar when later respiratory hospitalisations were restricted to asthma
      hospitalisations only. Recurrent hospitalisations for ARI in infancy
      significantly increase the risk of respiratory morbidity and asthma requiring
      hospitalisation after the age of 3 years in a dose-response fashion. The increase
      in relative risk is not modified by gestational age. Efforts to reduce the
      occurrence of infant ARI are likely to have significant public health benefits.

PMID- 26293502
TI  - Diagnosis of COPD before cardiac surgery.

PMID- 26293503
TI  - Severe pulmonary hypertension in lung disease: phenotypes and response to
      treatment.
AB  - Pulmonary hypertension (PH) due to lung disease (World Health Organization (WHO)
      group 3) is common, but severe PH, arbitrarily defined as mean pulmonary artery
      pressure >=35 mmHg is reported in only a small proportion. Whether these should
      be treated as patients in WHO group 1 (i.e. pulmonary arterial hypertension) with
      PH-targeted therapies is unknown. We compared the phenotypic characteristics and
      outcomes of 118 incident patients with severe PH and lung disease with 74
      idiopathic pulmonary arterial hypertension (IPAH) patients, all treated with
      pulmonary vasodilators. Lung disease patients were older, more hypoxaemic, and
      had lower gas transfer, worse New York Heart Association functional class and
      lower 6-min walking distance (6MWD) than IPAH patients. Poorer survival in those
      with lung disease was driven by the interstitial lung disease (ILD) cohort. In
      contrast to IPAH, where significant improvements in 6MWD and N-terminal pro-brain
      natruiretic peptide (NT-proBNP) occurred, PH therapy in severe PH lung disease
      did not lead to improvement in 6MWD or functional class, but neither was
      deterioration seen. NT-proBNP decreased from 2200 to 1596 pg.mL(-1) (p=0.015).
      Response varied by lung disease phenotype, with poorer outcomes in patients with
      ILD and emphysema with preserved forced expiratory volume in 1 s. Further study
      is required to investigate whether vasodilator therapy may delay disease
      progression in severe PH with lung disease.

PMID- 26293504
TI  - Matrix-Assisted Transplantation of Functional Beige Adipose Tissue.
AB  - Novel, clinically relevant, approaches to shift energy balance are urgently
      needed to combat metabolic disorders such as obesity and diabetes. One promising
      approach has been the expansion of brown adipose tissues that express uncoupling
      protein (UCP) 1 and thus can uncouple mitochondrial respiration from ATP
      synthesis. While expansion of UCP1-expressing adipose depots may be achieved in
      rodents via genetic and pharmacological manipulations or the transplantation of
      brown fat depots, these methods are difficult to use for human clinical
      intervention. We present a novel cell scaffold technology optimized to establish
      functional brown fat-like depots in vivo. We adapted the biophysical properties
      of hyaluronic acid-based hydrogels to support the differentiation of white
      adipose tissue-derived multipotent stem cells (ADMSCs) into lipid-accumulating,
      UCP1-expressing beige adipose tissue. Subcutaneous implantation of ADMSCs within
      optimized hydrogels resulted in the establishment of distinct UCP1-expressing
      implants that successfully attracted host vasculature and persisted for several
      weeks. Importantly, implant recipients demonstrated elevated core body
      temperature during cold challenges, enhanced respiration rates, improved glucose
      homeostasis, and reduced weight gain, demonstrating the therapeutic merit of this
      highly translatable approach. This novel approach is the first truly clinically
      translatable system to unlock the therapeutic potential of brown fat-like tissue
      expansion. 

PMID- 26293506
TI  - Anti-CD3/Anti-CXCL10 Antibody Combination Therapy Induces a Persistent Remission
      of Type 1 Diabetes in Two Mouse Models.
AB  - Anti-CD3 therapy of type 1 diabetes results in a temporary halt of its
      pathogenesis but does not constitute a permanent cure. One problem is the
      reinfiltration of islets of Langerhans with regenerated, autoaggressive
      lymphocytes. We aimed at blocking such a reentry by neutralizing the key
      chemokine CXCL10. Combination therapy of diabetic RIP-LCMV and NOD mice with anti
      CD3 and anti-CXCL10 antibodies caused a substantial remission of diabetes and was
      superior to monotherapy with anti-CD3 or anti-CXCL10 alone. The combination
      therapy prevented islet-specific T cells from reentering the islets of Langerhans
      and thereby blocked the autodestructive process. In addition, the local immune
      balance in the pancreas was shifted toward a regulatory phenotype. A sequential
      temporal inactivation of T cells and blockade of T-cell migration might
      constitute a novel therapy for patients with type 1 diabetes. 

PMID- 26293505
TI  - Exercise and Weight Loss Improve Muscle Mitochondrial Respiration, Lipid
      Partitioning, and Insulin Sensitivity After Gastric Bypass Surgery.
AB  - Both Roux-en-Y gastric bypass (RYGB) surgery and exercise can improve insulin
      sensitivity in individuals with severe obesity. However, the impact of RYGB with
      or without exercise on skeletal muscle mitochondria, intramyocellular lipids, and
      insulin sensitivity index (SI) is unknown. We conducted a randomized exercise
      trial in patients (n = 101) who underwent RYGB surgery and completed either a 6
      month moderate exercise (EX) or a health education control (CON) intervention. SI
      was determined by intravenous glucose tolerance test. Mitochondrial respiration
      and intramyocellular triglyceride, sphingolipid, and diacylglycerol content were
      measured in vastus lateralis biopsy specimens. We found that EX provided
      additional improvements in SI and that only EX improved cardiorespiratory
      fitness, mitochondrial respiration and enzyme activities, and cardiolipin profile
      with no change in mitochondrial content. Muscle triglycerides were reduced in
      type I fibers in CON, and sphingolipids decreased in both groups, with EX showing
      a further reduction in a number of ceramide species. In conclusion, exercise
      superimposed on bariatric surgery-induced weight loss enhances mitochondrial
      respiration, induces cardiolipin remodeling, reduces specific sphingolipids, and
      provides additional improvements in insulin sensitivity. 

PMID- 26293508
TI  - Automated adaptive inference of phenomenological dynamical models.
AB  - Dynamics of complex systems is often driven by large and intricate networks of
      microscopic interactions, whose sheer size obfuscates understanding. With limited
      experimental data, many parameters of such dynamics are unknown, and thus
      detailed, mechanistic models risk overfitting and making faulty predictions. At
      the other extreme, simple ad hoc models often miss defining features of the
      underlying systems. Here we develop an approach that instead constructs
      phenomenological, coarse-grained models of network dynamics that automatically
      adapt their complexity to the available data. Such adaptive models produce
      accurate predictions even when microscopic details are unknown. The approach is
      computationally tractable, even for a relatively large number of dynamical
      variables. Using simulated data, it correctly infers the phase space structure
      for planetary motion, avoids overfitting in a biological signalling system and
      produces accurate predictions for yeast glycolysis with tens of data points and
      over half of the interacting species unobserved. 

PMID- 26293507
TI  - Notch1 and Notch2 in Podocytes Play Differential Roles During Diabetic
      Nephropathy Development.
AB  - Notch pathway activation in podocytes has been shown to play an important role in
      diabetic kidney disease (DKD) development; however, the receptors and ligands
      involved in the process have not been identified. Here, we report that
      conditional deletion of Notch1 in podocytes using NPHS2(cre)Notch1(flox/flox)
      animals resulted in marked amelioration of DKD. On the contrary, podocyte
      specific genetic deletion of Notch2 had no effect on albuminuria and mesangial
      expansion. Notch1-null podocytes were protected from apoptosis and
      dedifferentiation in vitro, likely explaining the protective phenotype in vivo.
      Deletion of Notch1 in podocytes also resulted in an increase in Notch2
      expression, indicating an interaction between the receptors. At the same time,
      transgenic overexpression of Notch2 in podocytes did not induce phenotypic
      changes, while constitutive expression of Notch1 caused rapid development of
      albuminuria and glomerulosclerosis. In summary, our studies indicate that Notch1
      plays a distinct (nonredundant) role in podocytes during DKD development. 

PMID- 26293510
TI  - Extended release, 6-month formulations of leuprolide acetate for the treatment of
      advanced prostate cancer: achieving testosterone levels below 20 ng/dl.
AB  - INTRODUCTION: Luteinizing hormone-releasing hormone agonists such as leuprolide
      acetate (LA) are the most frequently utilized treatment of advanced prostate
      cancer as the regimen for achieving androgen deprivation therapy (ADT). The
      efficacy of LA is determined by extent of testosterone (T) suppression in
      prostate cancer patients. Although, the historical castrate T suppression target
      has been defined as < 50 ng/dl, this level may not be as low as required to
      deliver equivalent suppression as achieved by surgical castration. Recent studies
      have demonstrated that a T level as low as 20 ng/dl may produce improved clinical
      outcomes. AREAS COVERED: LA is available in long-acting formulations that deliver
      active drug over the course of 1-6 months from a single-dose administration. The
      technologies utilized to provide sustained drug delivery differ: one mode of
      administration uses microspheres, which encapsulate the drug and are injected as
      a suspension intramuscularly; another mode of administration uses a liquid
      polymer that creates a single, solid depot after injection subcutaneously. This
      article will review the safety and efficacy of both 6-month LA formulations, as
      well as their impact in prostate cancer treatment. EXPERT OPINION: As the
      understanding of optimal T castrate level evolves and may be refined pending new
      data from contemporaneous trials, achievement and maintenance of T levels well
      below 50 ng/dl may be important in evaluating potential differences in ADT
      regimens.

PMID- 26293511
TI  - Evolocumab in the treatment of dyslipidemia: pre-clinical and clinical
      pharmacology.
AB  - INTRODUCTION: Statins are the mainstay of lipid-lowering therapies targeted at
      reducing cardiovascular risk. However, they do not completely obviate risk, not
      all patients tolerate them, and they are not sufficiently effective in patients
      with very high plasma levels of low-density lipoprotein-cholesterol (LDL-C) such
      as those with familial hypercholesterolemia (FH) or patients with elevated plasma
      levels of lipoprotein(a) [Lp(a)]. Recent advances in the understanding of
      lipoprotein metabolism have led to the development of the proprotein convertase
      subtilisin/kexin type 9 (PCSK9) inhibitors including evolocumab , which lowers
      plasma levels of LDL-C by 50 - 75% as monotherapy or in combination with statin
      therapy. AREAS COVERED: We discuss in this review the rationale and background
      behind the development of evolocumab, and its pharmacodynamics and
      pharmacokinetics. We then discuss the current state-of-play of relevant clinical
      trials. EXPERT OPINION: The dramatic reduction in plasma levels of LDL-C
      attributable to evolocumab is anticipated to translate into lower rates of
      atherosclerotic cardiovascular disease, but this hypothesis remains to be proven.
      Also to be established are the long-term safety and economic benefits of
      evolocumab. PCSK9 inhibitors will also probably provide a valuable option for
      patients with statin intolerance, those with FH and patients with elevated plasma
      levels of Lp(a).

PMID- 26293512
TI  - Myelodysplastic syndromes following therapy with hypomethylating agents (HMAs):
      development of acute erythroleukemia may not influence assessment of treatment
      response.
AB  - This study followed 28 patients with myelodysplastic syndromes (MDS) who showed a
      rise of bone marrow (BM) erythroids to >= 50% following three cycles (1-60) of
      hypomethylating agent (HMA) therapy. If BM blasts were calculated as a percentage
      of non-erythroids, 12 (42.9%) patients met the diagnostic criteria for acute
      erythroleukemia, erythroid/myeloid (AEL). However, none of the patients showed
      clonal cytogenetic evolution or new mutations. When compared to 47 de novo AEL
      patients, these 12 patients were less anemic and thrombocytopenic, had less
      complex karyotypes (p = 0.044) and showed a longer survival, either calculated
      from diagnosis (p < 0.001) or from the time of AEL (p = 0.005). These findings
      illustrate that >= 50% erythroids may appear in BM post-HMA therapy, likely a
      combination of reduction of BM granulocytes (p < 0.001) and promotion of normal
      or abnormal erythroid proliferation. Enumeration of blasts as a percentage of non
      erythroid cells may lead to a diagnosis of AEL and mis-interpretation as disease
      progression.

PMID- 26293513
TI  - Tapentadol immediate-release for acute postbunionectomy pain: a phase 3,
      randomized, double-blind, placebo-controlled, parallel-group study in Taiwan.
AB  - OBJECTIVE: To evaluate the efficacy and safety of tapentadol immediate-release
      (IR) for treating acute pain following orthopedic bunionectomy surgery in a
      Taiwanese population. METHODS: This was a phase 3, randomized, double-blind,
      placebo-controlled, parallel-group bridging study in which Taiwanese patients (N
      = 60) with moderate-to-severe pain following bunionectomy were randomized (1:1:1)
      to receive tapentadol IR 50 or 75 mg or placebo orally every 4-6 hours over a 72
      hour period. The primary endpoint was the sum of pain intensity difference over
      48 hours (SPID48), analyzed using analysis of variance. RESULTS: Out of 60
      patients randomized (mainly women [96.7%]; median age 44 years), 41 (68.3%)
      completed the treatment. Mean SPID48 values were significantly higher for
      tapentadol IR (p <= 0.006: 50 mg, p <= 0.004: 75 mg) compared with placebo.
      Between-group differences in LS means of SPID48 (vs. placebo) were tapentadol IR
      50 mg: 105.6 (95% CI: 32.0; 179.2); tapentadol IR 75 mg: 126.6 (95% CI: 49.5;
      203.7). Secondary endpoints including SPID at 12, 24, and 72 hours, time to first
      use of rescue medication, cumulative distribution of responder rates, total pain
      relief and sum of total pain relief and sum of pain intensity difference at 12,
      24, 48, and 72 hours, and patient global impression of change showed numerically
      better results supporting that tapentadol IR (50 and 75 mg) was more efficacious
      than placebo in relieving acute pain. The most frequent treatment emergent
      adverse events reported in >= 10% patients in either group were dizziness,
      nausea, and vomiting. A limitation of this study may possibly include more
      controlled patient monitoring through 4-6 hour dosing intervals, which reflects
      optimal conditions and thus may not approximate real-world clinical practice.
      However, all treatment groups would be equally affected by such bias of frequent
      monitoring, if any, since it was a randomized and double-blind study.
      CONCLUSIONS: Tapentadol IR treatment significantly relieved acute postoperative
      pain and was well tolerated in a Taiwanese population. ClinicalTrials.gov
      identifier: NCT01813890.

PMID- 26293514
TI  - The role of platelets in inflammation.
AB  - There is growing recognition of the critical role of platelets in inflammation
      and immune responses. Recent studies have indicated that antiplatelet medications
      may reduce mortality from infections and sepsis, which suggests possible clinical
      relevance of modifying platelet responses to inflammation. Platelets release
      numerous inflammatory mediators that have no known role in haemostasis. Many of
      these mediators modify leukocyte and endothelial responses to a range of
      different inflammatory stimuli. Additionally, platelets form aggregates with
      leukocytes and form bridges between leukocytes and endothelium, largely mediated
      by platelet P-selectin. Through their interactions with monocytes, neutrophils,
      lymphocytes and the endothelium, platelets are therefore important coordinators
      of inflammation and both innate and adaptive immune responses. 

PMID- 26293515
TI  - Electrochemical Synthesis of Binary and Ternary Niobium-Containing Oxide
      Electrodes Using the p-Benzoquinone/Hydroquinone Redox Couple.
AB  - New electrochemical synthesis methods have been developed to obtain layered
      potassium niobates, KNb3O8 and K4Nb6O17, and perovskite-type KNbO3 as film-type
      electrodes. The electrodes were synthesized from aqueous solutions using the
      redox chemistry of p-benzoquinone and hydroquinone to change the local pH at the
      working electrode to trigger deposition of desired phases. In particular, the
      utilization of electrochemically generated acid via the oxidation of hydroquinone
      for inorganic film deposition was first demonstrated in this study. The layered
      potassium niobates could be converted to (H3O)Nb3O8 and (H3O)4Nb6O17 by cationic
      exchange, which, in turn, could be converted to Nb2O5 by heat treatment. The
      versatility of the new deposition method was further demonstrated for the
      formation of CuNb2O6 and AgNbO3, which were prepared by the deposition of KNb3O8
      and transition metal oxides, followed by thermal and chemical treatments.
      Considering the lack of solution-based synthesis methods for Nb-based oxide
      films, the methods reported in this study will contribute greatly to studies
      involving the synthesis and applications of Nb-based oxide electrodes. 

PMID- 26293519
TI  - Effect of food on the pharmacokinetics of piperaquine and dihydroartemisinin.
AB  - BACKGROUND AND OBJECTIVE: Piperaquine-dihydroartemisinin combination therapy has
      established efficacy for the treatment of malaria; however, a more comprehensive
      understanding of the pharmacokinetic properties and factors contributing to inter
      and intra-individual variability is critical to optimize clinical use. This
      study assessed the effects of food on the pharmacokinetics of combination
      piperaquine-dihydroartemisinin administration in healthy volunteers. METHODS:
      This was an open-label, single-dose, parallel-group study. Participants were
      randomly allocated to receive oral piperaquine-dihydroartemisinin either after an
      overnight fast or immediately after a standardized, high-fat, high-calorie meal.
      Blood samples were collected for analysis of plasma piperaquine and
      dihydroartemisinin concentrations, which were utilized for calculation of
      pharmacokinetic parameters, using a standard model-independent approach. RESULTS:
      Consumption of a high-fat, high-calorie meal resulted in substantial increases in
      the extent of exposure to piperaquine (ratio between area under the plasma
      concentration-time curve [AUC] values from 0 to 168 h in the fed and fasted
      states [AUC0-168 h FED/AUC0-168 h FASTED] = 299 %, 90 % confidence interval [CI]
      239-374 %). This likely reflects an increase in the oral bioavailability of the
      drug, directly related to the fat content of the meal. Co-administration of food
      was also found to result in both delayed and enhanced absorption of
      dihydroartemisinin (ratio between AUC values from time zero to infinity in the
      fed and states [AUCinfinity FED/AUCinfinity FASTED] = 142 %, 90 % CI 113-178 %;
      ratio between mean transit time [MTT] values in the fed and fasted states
      [MTTFED/MTTFASTED] = 135 %, 90 % CI 114-160 %). CONCLUSION: Although food was
      found to significantly impact on the pharmacokinetics of piperaquine and
      dihydroartemisinin, given the low fat content of standard meals within endemic
      regions and the anorexic effects of malaria infection, these results are unlikely
      to impact on the clinical utility of these drugs. However, co-administration of
      food with these anti-malarials by populations consuming a typical Western diet
      should be avoided to reduce the risk of toxic side effects. It is therefore a
      general recommendation that piperaquine-dihydroartemisinin not be administered
      within +/-3 h of food consumption.

PMID- 26293520
TI  - Higher risk of sulfonylurea-associated hypoglycemic symptoms in women with type 2
      diabetes mellitus.
AB  - BACKGROUND: Although some evidence suggests that women may be at greater risk for
      hypoglycemia, no conclusion has been reached, and female sex has not been taken
      into account in antidiabetic drug-induced hypoglycemia. This study aimed to
      determine whether females are at a higher risk of sulfonylurea (SU)-associated
      hypoglycemia in daily clinical practice. METHODS: The incidence of adverse
      reactions of SU was investigated in 2119 Japanese patients who participated in
      the Drug Event Monitoring project of the Japan Pharmaceutical Association, which
      was conducted in Kumamoto prefecture. A multiple logistic regression analysis was
      used to determine the association between the incidence of hypoglycemic symptoms
      and female sex, with adjusted odds ratios (ORs) and 95 % confidence intervals (95
      % CIs). RESULTS: Female sex was found to be significantly associated with
      hypoglycemic symptoms (female vs. male; OR 2.04; 95 % CI 1.22-3.41; p = 0.007).
      The concomitant use of other antihyperglycemic agents (>=2 vs. 0 concomitant
      drug; OR 2.80; 95 % CI 1.17-6.67; p = 0.021), a shorter duration of diabetes
      medication (<3 vs. >=24 months; OR 4.14; 95 % CI 1.06-16.14; p = 0.041) and a
      longer follow-up period (OR 1.02; 95 % CI 1.00-1.04; p = 0.041) were identified
      as risk factors for hypoglycemia that were specific to females. CONCLUSION: To
      the best of our knowledge, this is the first report to focus on female sex as a
      potential risk factor for SU-associated hypoglycemia. Our results support the
      importance of individualized therapy, which may be effective not only for
      reducing the risk of hypoglycemia in females but also the risk of its
      consequences, such as cardiovascular disease, dementia and increased mortality.

PMID- 26293522
TI  - What Is Happening in the Area of Device-Based Blood Pressure Treatment?

PMID- 26293521
TI  - Interactions between CYP3A5*3 and POR*28 polymorphisms and lipid lowering
      response with atorvastatin.
AB  - BACKGROUND AND OBJECTIVE: The polymorphic enzyme P450 oxidoreductase (POR)
      transfers electrons from nicotinamide adenine dinucleotide phosphate (NADPH) to
      cytochrome P450 (CYP) 3A enzyme s, which metabolize atorvastatin. This suggests
      that variations in the CYP3A5 and POR genes may influence the response to
      statins. We aimed to investigate the association and interactions between
      CYP3A5*3 and POR*28 polymorphisms and the lipid-lowering effects of atorvastatin
      in a Chinese population. METHODS: Genotypes were determined by polymerase chain
      reaction (PCR) with restriction fragment length polymorphism analysis and by PCR
      with direct sequencing analysis for 179 hyperlipidaemic patients treated with
      atorvastatin 20 mg once daily for 4 weeks. Serum levels of triglycerides (TGs),
      total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high
      density lipoprotein cholesterol (HDL-C) were determined before and after
      treatment. RESULTS: For the 179 patients (including 100 males), the variant
      allele frequencies of CYP3A5*3 and POR*28 were 73.75 and 41.62 %, respectively.
      Among all patients, no significant association was found between CYP3A5*3
      polymorphisms and TG, TC, LDL-C and HDL-C levels before and after treatment with
      20 mg of atorvastatin daily for 4 weeks. Homozygotes for the POR*28 T allele
      showed a significantly lower mean concentration of LDL-C than homozygotes for the
      POR*28 C allele (POR*28 TT vs POR*28 CC: 2.46 +/- 0.37 vs 2.69 +/- 0.49 mmol/L, P
      = 0.019) after treatment with atorvastatin 20 mg daily for 4 weeks. After
      adjustment for age, sex and body mass index, CYP3A5 non-expressors who were
      POR*28 wild-type homozygotes showed significantly higher mean TC and LDL-C levels
      than those who were POR*28 variant homozygotes, both at baseline (*3/CC vs *3/TT;
      TC: 7.30 +/- 0.73 vs 6.94 +/- 0.36 mmol/L, P = 0.026; LDL-C: 3.88 +/- 0.70 vs
      3.47 +/- 0.46 mmol/L, P = 0.009) and after atorvastatin treatment (*3/CC vs
      *3/TT; TC: 6.03 +/- 0.64 vs 5.69 +/- 0.34 mmol/L, P = 0.017; LDL-C: 2.80 +/- 0.62
      vs 2.43 +/- 0.40 mmol/L, P = 0.008). CYP3A5 non-expressors who were POR*28 wild
      type homozygotes showed significantly higher TC and LDL-C levels at baseline
      (*3/CC vs *1/CC; TC: 7.30 +/- 0.73 vs 6.95 +/- 0.41 mmol/L, P = 0.010; LDL-C:
      3.88 +/- 0.70 vs 3.55 +/- 0.39 mmol/L, P = 0.010) and showed higher TC levels
      after atorvastatin treatment (*3/CC vs *1/CC; 6.03 +/- 0.64 vs 5.73 +/- 0.27
      mmol/L, P = 0.012), in comparison with patients expressing CYP3A5 who were POR*28
      wild-type homozygotes. CYP3A5 non-expressors who were POR*28 heterozygotes showed
      significantly lower percentage changes in TC from baseline than those expressing
      CYP3A5 who were POR*28 heterozygotes (*3/CT vs *1/CT; 16.77 +/- 3.13 vs 18.40 +/-
      4.16 mmol/L, P = 0.031). CONCLUSION: POR*28 is associated with a poorer response
      to atorvastatin, but there is no association of the latter with CYP3A5*3. POR*28
      single nucleotide polymorphisms are associated with greater increases in the
      effect on plasma lipids in non-expressors of CYP3A5. Besides CYP3A5*3 genetic
      polymorphism, POR*28 genetic polymorphism might also be responsible for the
      marked interindividual variability in the lipid-lowering response to
      atorvastatin.

PMID- 26293523
TI  - Copper-catalyzed cyanation of aryl iodides with alpha-cyanoacetates via C-CN bond
      activation.
AB  - A Cu(I)-catalyzed cyanation reaction of aryl iodides with alpha-cyanoacetates is
      reported herein, which uses alpha-cyanoacetates as the nontoxic and easy-handling
      CN source through copper-mediated C-CN bond cleavage. This reaction enables
      access to aryl nitriles with an array of functional groups on the aromatic ring
      in good to excellent yields.

PMID- 26293541
TI  - The phospholipase A2 activity of peroxiredoxin 6 promotes cancer cell death
      induced by tumor necrosis factor alpha in hepatocellular carcinoma.
AB  - In this study, we used proteomic profiling to compare hepatocellular carcinoma
      (HCC) and peri-tumoral tissues to identify potential tumor markers of HCC. We
      identified eight differentially expressed proteins (>3-fold), including
      Peroxiredoxin 6 (PRDX6). PRDX6 is a bifunctional enzyme with both peroxidase and
      calcium-independent phospholipase A2 (iPLA2) activity. We found that peri-tumoral
      tissues expressed higher levels of PRDX6 mRNA (n = 59, P = 0.018) and protein (n
      = 265, P < 0.001) than HCC tissues, and that decreased expression of PRDX6 in HCC
      tissues was an independent risk factor indicating a poor prognosis (n = 145, P =
      0.007). Combining the examination of serum PRDX6 with alpha-fetoprotein improved
      the diagnostic sensitivity of tests for HCC compared to alpha-fetoprotein alone
      (85.0% vs 50.0%, n = 40). We found that PRDX6 induced S phase arrest in HCC cells
      and inhibited HCC tumorigenicity in mice injected with cancer cells. When treated
      with H2 O2 , PRDX6 inhibited apoptosis. When treated with tumor necrosis factor
      alpha (TNF-alpha), PRDX6 promoted apoptosis. Inhibition of iPLA2 activity of
      PRDX6 decreased the apoptosis induced by TNF-alpha. In conclusion, PRDX6
      inhibited the carcinogenesis of HCC, and the iPLA2 activity of PRDX6 promoted
      cancer cell death induced by TNF-alpha. (c) 2015 Wiley Periodicals, Inc.

PMID- 26293542
TI  - A salutogenic program to enhance sense of coherence and quality of life for older
      people in the community: A feasibility randomized controlled trial and process
      evaluation.
AB  - OBJECTIVE: To determine the feasibility of a salutogenesis-based self-care
      program on quality of life, sense of coherence, activation and resilience among
      older community dwellers. METHODS: This is a feasibility randomized controlled
      trial. Sixty-four older community-dwellers were recruited from a Singapore senior
      activity center and randomly assigned to intervention and control groups. The
      intervention group attended a 12-week Resource Enhancement and Activation
      Program. The outcomes were assessed with the Chinese versions of World Health
      Organization Quality of Life Scale, Sense of Coherence, Patient Activation
      Measure, and Connor-Davidson Resilience Scale. Process evaluation was conducted
      using focus groups with the intervention group. RESULTS: At the end of the
      program, the intervention group showed significant improvement in the Sense of
      Coherence scale and the psychological subscale of the WHO Quality of Life scale
      compared with the control group. Three themes emerged from the process
      evaluation: participation in the program, reflection on the experience, and
      improving the experience. CONCLUSION: A salutogenic self-care approach could be a
      potential health promotion strategy for older people. PRACTICE IMPLICATIONS: With
      improved sense of coherence and psychological aspect of quality of life, older
      people's self-care ability may improve, leading to better health and better
      quality of life.

PMID- 26293543
TI  - Computational classification models for predicting the interaction of compounds
      with hepatic organic ion importers.
AB  - Hepatic transporters, a major determinant of pharmacokinetics, have been used to
      profile drug properties like efficacy. Among hepatic transporters, importers
      alter the concentration of the drug by facilitating the transport of a drug into
      a cell. Despite vast pharmacokinetic studies, the interacting mechanisms of the
      importers with its substrates or inhibitors are not well understood. Hence, we
      developed compound binary classification models of whether a compound is binder
      or nonbinder to a hepatic transporter with experimental data of 284 compounds for
      four representative hepatic importers, OATP1B1, OATP1B3, OAT2, and OCT1. Support
      Vector Machine (SVM) along with Genetic Algorithm (GA) was used to construct the
      classification models of binder versus nonbinder for each target importer. To
      construct the models, we prepared two data sets, a training data set from Fujitsu
      database (284 compounds) and an external validation data set from ChEMBL database
      (1738 compounds). Since an experimental classification criterion between binder
      and nonbinder has some ambiguity, there is an intrinsic limitation to expect high
      predictability of the binary classification models developed with the
      experimental data. The predictability of the classification models calculated
      with external validation sets were obtained as 77.72%, 84.31%, 84.21%, and 76.38
      for OATP1B1, OATP1B3, OAT2, and OCT1, respectively. 

PMID- 26293544
TI  - Selection of reference genes for quantitative real-time polymerase chain reaction
      in porcine embryos.
AB  - To study gene expression and to determine distinctive characteristics of embryos
      produced by different methods, normalisation of the gene(s) of interest against
      reference gene(s) has commonly been employed. Therefore, the present study aimed
      to assess which reference genes tend to express more stably in single porcine
      blastocysts produced in vivo (IVO) or by parthenogenetic activation (PA), in
      vitro fertilisation (IVF) and somatic cell nuclear transfer (SCNT) using
      different analysis programs, namely geNorm, Normfinder and Bestkeeper. Commonly
      used reference genes including 18S rRNA (18S), H2A histone family, member Z
      (H2A), hypoxanthine phosphoribosyltransferase1 (HPRT1), glyceraldehyde-3
      phosphate dehydrogenase (GAPDH), ribosomal protein 4 (RPL4), peptidylprolyl
      isomerase A (PPIA), beta actin (ACTB), succinate dehydrogenase complex, subunit A
      (SDHA) and hydroxymethylbilane synthase (HMBS2) were analysed; most of them
      resulted in significantly (P<0.05) different cycle threshold (CT) values in
      porcine embryos except for SDHA and H2A. In evaluation of stable reference genes
      across in vivo and in vitro porcine blastocysts, three kinds of programs showed
      slightly different results; however, there were similar patterns about the
      rankings of more or less stability overall. In conclusion, SDHA and H2A were
      determined as the most appropriate reference genes for reliable normalisation in
      order to find the comparative gene expression in porcine blastocysts produced by
      different methods, whereas 18S was regarded as a less-stable reference gene. The
      present study has evaluated the stability of commonly used reference genes for
      accurate normalisation in porcine embryos to obtain reliable results.

PMID- 26293545
TI  - Glycation, carbonyl stress and AGEs inhibitors: a patent review.
AB  - INTRODUCTION: The glycation process, comprising a series of reactions, results in
      the formation of heterogeneous adducts, known as advanced glycation end products
      (AGEs). AGEs are involved in several pathologies, including diabetes-associated
      late complications, atherosclerosis, Alzheimer's disease and inflammatory
      arthritis. Several inhibitors of AGEs and/or reactive carbonyl species have been
      identified from various sources, including natural products and synthetic
      molecules, and have been investigated for their mechanism of action. AREAS
      COVERED: This review covers the literature on AGEs inhibitors published as
      patents between 2001 and 2014. Initially, the earlier reported molecules with
      AGEs inhibitory properties, their mechanism of actions and reported adverse
      effects are discussed. The main focus has been on the chemical structures,
      methods for evaluation of the activity, modes of action, pharmacokinetics and
      therapeutic outcomes. The potential of these AGEs inhibitors in the treatment and
      management of a number of diseases are also discussed in this review. EXPERT
      OPINION: The reactive carbonyl species and AGEs have recently emerged as novel
      therapeutic targets for the prevention and treatment of several diseases.
      Currently, the major concerns with the use of AGEs inhibitors as therapeutic
      agents are low effectiveness, poor pharmacokinetics and undesirable side effects.
      Many of the AGEs inhibitors reviewed here possess potent antiglycation activity
      and are devoid of undesirable side effects. These small molecules inhibitors can,
      therefore, serve as scaffolds for the development and designing of new AGEs
      inhibitors as clinical agents.

PMID- 26293546
TI  - Prenatal Exposure to Phthalic Acid Induces Increased Blood Pressure, Oxidative
      Stress, and Markers of Endothelial Dysfunction in Rat Offspring.
AB  - Previous studies have reported the harmful effects of exposure to phthalic acid
      (PA) on heart. No studies have reported the effects of prenatal PA exposure on
      the structure or function of heart. The current study aimed to investigate the
      effects of prenatal PA exposure on the markers of oxidative stress and cardiac
      structure in rats' offspring. Twenty-four pregnant rats were randomly categorized
      into three groups of control, exposed to 2.5 and 5 % PA. The morphometric
      properties of coronary arteries, markers of oxidative stress, and NOS activity
      were measured in offspring rats. By a dose-dependent manner, the body weight
      (BW), heart weight (HW), and HW/BW of the intervention groups were reduced and
      their heart rate and blood pressure were conversely increased compared to the
      control group. Also, the wall thickness, cross-sectional area of the aorta and
      septal branch of the descending left coronary artery were significantly increased
      in the intervention group. In addition, PA significantly increased the level of
      malondialdehyde and decreased the level of superoxide dismutase and glutathione
      peroxidase, compared to the control group. This study revealed that prenatal
      exposure of rats to PA causes vascular dysfunction, increasing oxidative stress,
      and reduction in cardiac nitric oxide synthetase activity among offspring rats.

PMID- 26293547
TI  - Atomic pair distribution function: a revolution in the characterization of
      nanostructured pharmaceuticals.

PMID- 26293549
TI  - Discussion.

PMID- 26293548
TI  - Injectable shear-thinning hydrogels used to deliver endothelial progenitor cells,
      enhance cell engraftment, and improve ischemic myocardium.
AB  - OBJECTIVES: The clinical translation of cell-based therapies for ischemic heart
      disease has been limited because of low cell retention (<1%) within, and poor
      targeting to, ischemic myocardium. To address these issues, we developed an
      injectable hyaluronic acid (HA) shear-thinning hydrogel (STG) and endothelial
      progenitor cell (EPC) construct (STG-EPC). The STG assembles as a result of
      interactions of adamantine- and beta-cyclodextrin-modified HA. It is shear
      thinning to permit delivery via a syringe, and self-heals upon injection within
      the ischemic myocardium. This directed therapy to the ischemic myocardial border
      zone enables direct cell delivery to address adverse remodeling after myocardial
      infarction. We hypothesize that this system will enhance vasculogenesis to
      improve myocardial stabilization in the context of a clinically translatable
      therapy. METHODS: Endothelial progenitor cells (DiLDL(+) VEGFR2(+) CD34(+)) were
      harvested from adult male rats, cultured, and suspended in the STG. In vitro
      viability was quantified using a live-dead stain of EPCs. The STG-EPC constructs
      were injected at the border zone of ischemic rat myocardium after acute
      myocardial infarction (left anterior descending coronary artery ligation). The
      migration of the enhanced green fluorescent proteins from the construct to
      ischemic myocardium was analyzed using fluorescent microscopy. Vasculogenesis,
      myocardial remodeling, and hemodynamic function were analyzed in 4 groups:
      control (phosphate buffered saline injection); intramyocardial injection of EPCs
      alone; injection of the STG alone; and treatment with the STG-EPC construct.
      Hemodynamics and ventricular geometry were quantified using echocardiography and
      Doppler flow analysis. RESULTS: Endothelial progenitor cells demonstrated
      viability within the STG. A marked increase in EPC engraftment was observed 1
      week postinjection within the treated myocardium with gel delivery, compared with
      EPC injection alone (17.2 +/- 0.8 cells per high power field (HPF) vs 3.5 cells
      +/- 1.3 cells per HPF, P = .0002). A statistically significant increase in
      vasculogenesis was noted with the STG-EPC construct (15.3 +/- 5.8 vessels per
      HPF), compared with the control (P < .0001), EPC (P < .0001), and STG (P < .0001)
      groups. Statistically significant improvements in ventricular function, scar
      fraction, and geometry were noted after STG-EPC treatment compared with the
      control. CONCLUSIONS: A novel injectable shear-thinning HA hydrogel seeded with
      EPCs enhanced cell retention and vasculogenesis after delivery to ischemic
      myocardium. This therapy limited adverse myocardial remodeling while preserving
      contractility.

PMID- 26293550
TI  - Is the extraction by Whatman FTA filter matrix technology and sequencing of large
      ribosomal subunit D1-D2 region sufficient for identification of clinical fungi?
AB  - Although conventional identification of pathogenic fungi is based on the
      combination of tests evaluating their morphological and biochemical
      characteristics, they can fail to identify the less common species or the
      differentiation of closely related species. In addition these tests are time
      consuming, labour-intensive and require experienced personnel. We evaluated the
      feasibility and sufficiency of DNA extraction by Whatman FTA filter matrix
      technology and DNA sequencing of D1-D2 region of the large ribosomal subunit gene
      for identification of clinical isolates of 21 yeast and 160 moulds in our
      clinical mycology laboratory. While the yeast isolates were identified at species
      level with 100% homology, 102 (63.75%) clinically important mould isolates were
      identified at species level, 56 (35%) isolates at genus level against fungal
      sequences existing in DNA databases and two (1.25%) isolates could not be
      identified. Consequently, Whatman FTA filter matrix technology was a useful
      method for extraction of fungal DNA; extremely rapid, practical and successful.
      Sequence analysis strategy of D1-D2 region of the large ribosomal subunit gene
      was found considerably sufficient in identification to genus level for the most
      clinical fungi. However, the identification to species level and especially
      discrimination of closely related species may require additional analysis. 

PMID- 26293551
TI  - Direct Admission to Hospital: A Mixed Methods Survey of Pediatric Practices,
      Benefits, and Challenges.
AB  - BACKGROUND: Direct admissions account for 25% of pediatric unscheduled
      hospitalizations. Despite this, our knowledge of direct admission practices and
      safety is limited. This study aimed to characterize direct admission practices,
      benefits, and challenges at a diverse sample of hospitals and to identify
      diagnoses most appropriate for this admission approach. METHODS: We conducted a
      national survey at a stratified random sample of 177 US hospitals using both
      closed and open-ended questions. Descriptive statistics were calculated to
      summarize numeric responses, while qualitative content analysis was performed to
      identify emergent themes. RESULTS: Responses were received from 108 hospitals
      (61%). Hospitals represented all geographic regions and employed varied emergency
      medicine and inpatient care models. One hundred three respondents (95%) reported
      that their hospitals accepted direct admissions, and 45 (50%) expressed the view
      that more children should be admitted directly. Perceived benefits included the
      following: improved efficiency; patient and physician satisfaction; earlier
      access to pediatric-specific care; continuity of care; and reduced risk of
      nosocomial infection. Risks and challenges included the following: difficulties
      determining admission appropriateness; inconsistent processes; provision of
      timely care; and patient safety. Populations and diagnoses reported as most
      appropriate and inappropriate for direct admission varied considerably across
      respondents. CONCLUSIONS: While respondents described benefits of direct
      admission for both patients and health care systems, many also reported
      challenges and safety concerns. Our results may inform subsequent epidemiologic
      and patient-centered outcomes research to evaluate the safety and effectiveness
      of direct admissions.

PMID- 26293552
TI  - Antimicrobial effect and biocompatibility of novel metallic nanocrystalline
      implant coatings.
AB  - AIM: The present in vitro study was designed to evaluate the surface
      characteristics, biocompatibilities and antimicrobial effects of experimental
      titanium implant surfaces, coated by nanocrystalline silver, copper, and bismuth.
      Biocompatible and antimicrobial implant modifications could result in reduced
      biofilm formation on implant surfaces and therefore in less periimplant
      inflammation. FINDINGS: Titanium discs (thickness 1 mm and 12 mm in diameter)
      were coated by pulsed magnetron-sputtering of nanocrystalline metals (bismuth,
      copper, and silver). Bismuth coatings revealed higher surface roughness values in
      comparison to silver and copper coatings via atomic force microscopy. Ion release
      after 168 h in culture medium was analyzed by inductively coupled plasma-mass
      spectrometry and showed significant different amounts of released copper (>120
      000 ug/L), silver (550 ug/L) or bismuth (80 ug/L). No cytotoxic effect on HaCaT
      cell proliferation was detected on the uncoated Ti/TiO2 reference surfaces, the
      bismuth coatings and silver coatings. In contrast, copper-coated discs showed a
      strong cytotoxic effect. All three coatings exhibited antimicrobial effects by
      trend in the fluorometric Resazurin testing and significant localized
      antibacterial effects in live/dead microscopy after incubation of the specimens
      for 150 min in bacterial solution of S. epidermidis. CONCLUSIONS: The tested
      metallic implant coatings (silver and bismuth) allowed surface modifications that
      may improve therapeutic approaches to biofilm prevention on dental implants. (c)
      2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2015. (c)
      2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1571
      1579, 2016.

PMID- 26293553
TI  - Transcriptional Responses and Mechanisms of Copper-Induced Dysfunctional
      Locomotor Behavior in Zebrafish Embryos.
AB  - Copper-induced delayed hatching and dysfunctional movement had been reported
      previously, and unbalanced free copper was found in the body of humans with
      Alzheimer's disease and other neural diseases, but details of the underlying
      mechanisms are still unknown. In this study, zebrafish (Danio rerio) embryos
      exposed to over 3.9 MUM of copper-exhibited delayed hatching and significantly
      dysfunctional movement. Using high-throughput in situ hybridization screening and
      by conducting an in-depth analysis of gene characterization in embryos exposed to
      copper, we found that copper caused neural crest defects from the initiation
      stage of neurogenesis, and embryos younger than the 70% epiboly stage were
      sensitive to copper toxicity. The myelination of Schwann cells, other than
      melanophores, cartilage, and neurons, was inhibited by copper during
      neurogenesis. In addition, axon guidance was blocked by copper. Downregulated
      cdx4-hox might have contributed to the neurogenesis-related defects. Moreover,
      copper inhibited the differentiation of muscle fibers and myotomes but not the
      specification of muscle progenitors. In summary, our data reveal a novel
      molecular mechanism for copper-inhibited locomotor behavior in embryos, in which
      copper blocks functional muscle fiber specification during myogenesis and
      inhibits the specification of axons and Schwann cell myelination during
      neurogenesis. A combination of these processes results in dysfunctional locomotor
      behavior in zebrafish embryos exposed to copper.

PMID- 26293555
TI  - Updated recommendations on the management of gastrointestinal disturbances during
      iron chelation therapy with Deferasirox in transfusion dependent patients with
      myelodysplastic syndrome - Emphasis on optimized dosing schedules and new
      formulations.
AB  - Myelodysplastic syndromes (MDS) are oligoclonal hematopoietic disorders
      characterized by peripheral cytopenias with anemias being the most prevalent
      feature. The majority of patients will depend on regular transfusions of packed
      red blood cells (PRBC) during the course of the disease. Particularly patients
      with MDS and low risk for transformation into acute myeloid leukemia and low risk
      of early death will receive PRBC transfusions on a regular basis, which puts them
      at high risk for transfusional iron overload. Transfusion dependence has been
      associated with negative impact on organ function and reduced life expectancy.
      Recently, several retrospective but also some prospective studies have indicated,
      that transfusion dependent patients with MDS might benefit from consequent iron
      chelation with regard to morbidity and mortality. However, low treatment
      adherence due to adverse events mainly gastrointestinal in nature is an important
      obstacle in achieving sufficient iron chelation in MDS patients. Here, we will
      summarize and discuss the existing data on Deferasirox in low risk MDS published
      so far and provide recommendations for optimal management of gastrointestinal
      adverse events during iron chelation aiming at improving treatment compliance
      and, hence, sufficiently removing excess iron from the patients. 

PMID- 26293554
TI  - Chronic Exposure to Particulate Chromate Induces Premature Centrosome Separation
      and Centriole Disengagement in Human Lung Cells.
AB  - Particulate hexavalent chromium (Cr(VI)) is a well-established human lung
      carcinogen. Lung tumors are characterized by structural and numerical chromosome
      instability. Centrosome amplification is a phenotype commonly found in solid
      tumors, including lung tumors, which strongly correlates with chromosome
      instability. Human lung cells exposed to Cr(VI) exhibit centrosome amplification
      but the underlying phenotypes and mechanisms remain unknown. In this study, we
      further characterize the phenotypes of Cr(VI)-induced centrosome abnormalities.
      We show that Cr(VI)-induced centrosome amplification correlates with numerical
      chromosome instability. We also show chronic exposure to particulate Cr(VI)
      induces centrosomes with supernumerary centrioles and acentriolar centrosomes in
      human lung cells. Moreover, chronic exposure to particulate Cr(VI) affects the
      timing of important centriolar events. Specifically, chronic exposure to
      particulate Cr(VI) causes premature centriole disengagement in S and G2 phase
      cells. It also induces premature centrosome separation in interphase. Altogether,
      our data suggest that chronic exposure to particulate Cr(VI) targets the protein
      linkers that hold centrioles together. These centriolar linkers are important for
      key events of the centrosome cycle and their premature disruption might underlie
      Cr(VI)-induced centrosome amplification. 

PMID- 26293556
TI  - Time for action on atrial fibrillation.

PMID- 26293557
TI  - Preventing Alzheimer's disease is difficult.

PMID- 26293558
TI  - Corrections.

PMID- 26293559
TI  - Risks of stenting in patients with extracranial and intracranial vertebral artery
      stenosis.

PMID- 26293560
TI  - Fighting cerebral palsy in Africa.

PMID- 26293561
TI  - Peter Rothwell: aspirin(g) physician with a little stroke of genius.

PMID- 26293562
TI  - Sandrine Andrieu.

PMID- 26293563
TI  - Testing times ahead.

PMID- 26293564
TI  - The dying of the light.

PMID- 26293566
TI  - Innate and adaptive immune responses in the CNS.
AB  - Almost every disorder of the CNS is said to have an inflammatory component, but
      the precise nature of inflammation in the CNS is often imprecisely defined, and
      the role of CNS-resident cells is uncertain compared with that of cells that
      invade the tissue from the systemic immune compartment. To understand
      inflammation in the CNS, the term must be better defined, and the response of
      tissue to disturbances in homoeostasis (eg, neurodegenerative processes) should
      be distinguished from disorders in which aberrant immune responses lead to CNS
      dysfunction and tissue destruction (eg, autoimmunity). Whether the inflammatory
      tissue response to injury is reparative or degenerative seems to be dependent on
      context and timing, as are the windows of opportunity for therapeutic
      intervention in inflammatory CNS diseases. 

PMID- 26293567
TI  - Mitochondrial dysfunction and seizures: the neuronal energy crisis.
AB  - Seizures are often the key manifestation of neurological diseases caused by
      pathogenic mutations in 169 of the genes that have so far been identified to
      affect mitochondrial function. Mitochondria are the main producers of ATP needed
      for normal electrical activities of neurons and synaptic transmission.
      Additionally, they have a central role in neurotransmitter synthesis, calcium
      homoeostasis, redox signalling, production and modulation of reactive oxygen
      species, and neuronal death. Hypotheses link mitochondrial failure to seizure
      generation through changes in calcium homoeostasis, oxidation of ion channels and
      neurotransmitter transporters by reactive oxygen species, a decrease in neuronal
      plasma membrane potential, and reduced network inhibition due to interneuronal
      dysfunction. Seizures, irrespective of their origin, represent an excessive acute
      energy demand in the brain. Accordingly, secondary mitochondrial dysfunction has
      been described in various epileptic disorders, including disorders that are
      mainly of non-mitochondrial origin. An understanding of the reciprocal relation
      between mitochondrial dysfunction and epilepsy is crucial to select appropriate
      anticonvulsant treatment and has the potential to open up new therapeutic
      approaches in the subset of epileptic disorders caused by mitochondrial
      dysfunction. 

PMID- 26293568
TI  - The Effectiveness of Mobile Phone-Based Care for Weight Control in Metabolic
      Syndrome Patients: Randomized Controlled Trial.
AB  - BACKGROUND: Overweight and obesity, due to a Westernized diet and lack of
      exercise, are serious global problems that negatively affect not only personal
      health, but national economies as well. To solve these problems, preventative
      based approaches should be taken rather than medical treatments after the
      occurrence of disease. The improvement of individual life habits, through
      continuous care, is thus a paramount, long-term treatment goal. This study
      describes the effects of ubiquitous health care (uHealth care) or SmartCare
      services in the treatment of weight loss and obesity. OBJECTIVE: The aim of this
      study is to evaluate the effect of SmartCare services on weight loss compared to
      the effects of existing outpatient treatments in obese patients with metabolic
      syndrome. METHODS: Metabolic syndrome patients who met the inclusion/exclusion
      criteria were enrolled in the study and randomized into an intervention or
      control group. The intervention group was provided with remote monitoring and
      health care services in addition to the existing treatment. The control group was
      provided with only the existing treatment. Pedometers were given to all of the
      patients. Additionally, mobile phones and body composition monitors were provided
      to the intervention group while body weight scales were provided to the control
      group. The patients visited the hospitals at 12 and 24 weeks following the
      baseline examination to receive efficacy and safety evaluations. RESULTS: Mean
      weight reduction from baseline to week 24 was measured as a primary efficacy
      evaluation parameter and was found to be 2.21 kg (SD 3.60) and 0.77 kg (SD 2.77)
      in the intervention and control group, respectively. The intervention group had a
      larger decrement compared to the control group (P<.001). Among the secondary
      efficacy evaluation parameters, body mass index (BMI) (P<.001), body fat rate
      (P=.001), decrement of waist measurement (P<.001), and diet habit (P=.012)
      improvement ratings from baseline to week 24 were found to be superior in the
      intervention group compared with the control group. The proportion of patients
      whose body weight decreased by >=10%, lipid profiles, blood pressure, prevalence
      of metabolic syndrome, change in the number of metabolic syndrome elements,
      smoking rate, drinking rate, and physical activity were not statistically
      significant between the groups. CONCLUSIONS: The efficacy of SmartCare services
      was confirmed as the intervention group that received both SmartCare services and
      the existing treatment had superior results compared with the control group that
      only received the existing treatment. Importantly, no specific problems with
      respect to safety concerns were observed. SmartCare service is thus an effective
      way to control the weight of obese patients with metabolic syndrome. TRIAL
      REGISTRATION: Clinicaltrials.gov NCT01344811;
      https://clinicaltrials.gov/ct2/show/NCT01344811 (Archived by Webcite at
      http://www.webcitation.org/6alT2MmIB).

PMID- 26293569
TI  - Older age is associated with greater central aortic blood pressure following the
      exercise stress test in subjects with similar brachial systolic blood pressure.
AB  - Brachial systolic pressure (BSP) is often monitored during exercise by the stress
      test; however, central systolic pressure (CSP) is thought to be a more direct
      measure of cardiovascular events. Although some studies reported that exercise
      and aging may play roles in changes of both BSP and CSP, the relationship between
      BSP and CSP with age following the exercise stress test remains unclear. The aim
      of this study was to evaluate the effect of age on the relationship between BSP
      and CSP measured after exercise. Ninety-six subjects underwent the diagnostic
      treadmill exercise stress test, and we retrospectively divided them into the
      following 3 groups by age: the younger age group (43 +/- 4 years), middle age
      group (58 +/- 4 years), and older age group (70 +/- 4 years). Subjects exercised
      according to the Bruce protocol, to achieve 85 % of their age-predicted maximum
      heart rate or until the appearance of exercise-associated symptoms. BSP, CSP, and
      pulse rate (PR) were measured using a HEM-9000AI (Omron Healthcare, Japan) at
      rest and after exercise. BSP, CSP, and PR at rest were not significantly
      different among the 3 groups (p = 0.92, 0.21, and 0.99, respectively). BSP and PR
      immediately after exercise were not significantly different among the groups (p =
      0.70 and 0.38, respectively). However, CSP immediately after exercise was 144 +/-
      18 mmHg (younger age), 149 +/- 17 mmHg (middle age), and 158 +/- 19 mmHg (older
      age). CSP in the older age group was significantly higher than that in the
      younger age group (p < 0.01). Despite similar BSPs in all age groups after
      exercise, CSP was higher in the older age group. Therefore, older subjects have a
      higher CSP after exercise, which is not readily assessed by conventional
      measurements of BSP. 

PMID- 26293571
TI  - Enteroscopic findings of Celiac Disease and their correlation with mucosal
      histopathologic changes.
AB  - BACKGROUND AND AIMS: Single Balloon Enteroscopy enables us to examine the small
      bowel for various diseases. It provides a view of the intestinal mucosa with
      biopsy capability, which may be helpful in search of a mucosal disease such as
      Celiac Disease. Celiac Disease is a proximal enteropathy developed in genetically
      susceptible individuals to wheat protein gluten. Examination of the duodenum and
      proximal jejunum are mostly diagnostic. We aimed to review enteroscopic findings
      of the patients with Celiac Disease. PATIENTS AND METHODS: Consecutive adult
      patients (>18y) who needed intestinal or duodenal biopsy for the diagnosis of the
      Celiac Disease were included. Single Balloon Enteroscopy system was used to enter
      the proximal jejunum. All of the patients had biopsies in order to diagnose
      Celiac Disease. RESULTS: Single Balloon Enteroscopy was performed in 33 patients.
      Twenty two (66.7%) subjects were diagnosed as Celiac Disease. The most common
      endoscopic abnormality in Celiac Disease was mucosal atrophy in 20 patients
      (90.9%), continuous involvement was the most common presentation (36.4%). All of
      the patients with Celiac Disease exhibited at least one endoscopic change.
      CONCLUSIONS: This study confirmed the patchy nature of the disease with mostly
      diffuse involvement of the small bowel. However, any endoscopic abnormality can
      be found in every patient with Celiac Disease. Analysis of images from either
      conventional upper endoscopy or capsule endoscopy may aid the diagnosis.

PMID- 26293570
TI  - Effects of liraglutide, a glucagon-like peptide-1 analog, on left ventricular
      remodeling assessed by cardiac magnetic resonance imaging in patients with acute
      myocardial infarction undergoing primary percutaneous coronary intervention.
AB  - The clinical efficacy of glucagon-like peptide-1 (GLP-1) analogs in patients with
      acute myocardial infarction (AMI) is uncertain. The purpose of the present study
      was to evaluate the effects of the GLP-1 analog liraglutide on left ventricular
      (LV) remodeling in patients with AMI. We retrospectively evaluated the effects of
      liraglutide on LV remodeling assessed by cardiac magnetic resonance imaging
      (CMRI) in 15 patients with type 2 diabetes who were successfully treated with
      primary percutaneous coronary intervention (PCI) for AMI. Patients were divided
      into two groups based on their hypoglycemic medication: liraglutide use (group L;
      n = 6) or standard therapy (group S; n = 9). The CMRI findings in the early phase
      and at the 6-month follow-up were compared. At the 6-month follow-up, group S
      showed increases in LV end-diastolic (from 64 to 74 mL/m(2), p = 0.08) and end
      systolic (from 38 to 45 mL/m(2), p = 0.13) volume indexes, whereas no such
      increase was observed in group L. The LV mass index (LVMI) was significantly
      smaller in group L than in group S at baseline (64 vs. 75 g/m(2), p = 0.05) and
      at follow-up (56 vs. 78 g/m(2), p = 0.009). Multivariate regression analysis
      showed that liraglutide use was an independent negative predictor of LVMI (beta =
      -0.720, p = 0.003). In conclusion, liraglutide may be able to prevent the
      progression of LV remodeling and is associated with a lower LV mass in diabetic
      patients with AMI undergoing primary PCI. 

PMID- 26293572
TI  - Ethical requirements for musculoskeletal research involving human subjects.

PMID- 26293573
TI  - The effect of the facilitated tucking position in reducing vaccination-induced
      pain in newborns.
AB  - BACKGROUND: This study was conducted to evaluate the pain perceptions of newborns
      during the hepatitis B (HBV) vaccinations performed in the facilitated tucking
      position and the classical holding position, respectively. METHODS: The
      randomized controlled experimental study was conducted between 1 September 2014
      and 30 December 2014 at the neonatal intensive care unit of a Turkish university
      hospital. One group of infants was held in the facilitated tucking position (the
      treatment group; n = 30) during HBV vaccination; infants in the other group were
      held in the classical holding position (the control group; n = 30) during HBV
      vaccination. The Neonatal Infant Pain Scale (NIPS) scores of the infants in the
      treatment and control groups were compared during procedure. Also, the infants'
      physiological parameters were compared before, during, and after the procedure.
      Descriptive statistics, a chi-square test, and an independent samples t-test were
      used to assess the data. RESULTS: The mean pain scores of infants vaccinated in
      the facilitated tucking position (2.83 +/- 1.18) were significantly statistically
      lower than the scores of infants vaccinated in the classical holding position
      (6.47 +/- 1.07) (p < 0.05). CONCLUSIONS: The pain perceptions of newborns held in
      the facilitated tucking position during HBV vaccination were lower. The
      facilitated tucking position, a non-pharmacological method, is recommended as an
      effective and useful method for reducing pain during the procedure.

PMID- 26293574
TI  - Unraveling the Role of Huntingtin in Breast Cancer Metastasis.
AB  - BACKGROUND: Huntingtin (HTT) is mutated in Huntington's disease but is
      ubiquitously expressed, and mutant HTT influences cancer progression. We
      investigated wild-type HTT function during breast cancer. METHODS: We analyzed
      HTT and ZO1 expression as well as the HTT phosphoserine 421-activated form (S421
      P-HTT) in human breast cancer tissues by quantitative reverse transcription
      polymerase chain reaction and immunohistochemistry. We performed in vitro
      migration and invasion assays as well as in vivo tail vein injections of the
      metastatic 4T1 cells in BALB/c mice (n = 11 per group). We analyzed tumor
      progression in knock-in mice with modified S421 crossed with the MMTV-PyVT
      mammary cancer model (at least n = 12 per group). Data were analyzed with
      unpaired t tests, analysis of variance, Pearson or Spearman correlation, and Mann
      Whitney or Kruskal-Wallis tests. All statistical tests were two-sided. RESULTS:
      Levels of HTT and of S421-P-HTT are abnormally low in poorly differentiated and
      metastatic human breast cancers. HTT expression is downregulated in invasive
      compared with in situ carcinoma (P < .001). In BALB/c mice, silencing of HTT
      promotes lung colonization by a metastatic mammary cancer cell line (P = .005)
      and S421-unphosphorylatable-HTT accelerates cancer progression. HTT interacts
      with ZO1 and regulates both its expression and its localization to tight
      junctions. In human breast tumors, the patterns of HTT and ZO1 expression are
      similar (Pearson correlation coefficient = 0.66, P < .001). CONCLUSIONS: HTT may
      inhibit breast tumor dissemination through maintenance of ZO1 at tight junctions.
      Downregulation of HTT transcript and protein levels is a prognostic factor for
      poor prognosis and metastasis development.

PMID- 26293575
TI  - Reliever salbutamol use as a measure of exacerbation risk in chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Debate exists regarding which endpoints most sensitively reflect day
      to-day variation in chronic obstructive pulmonary disease (COPD) symptoms and are
      most useful in clinical practice to predict COPD exacerbations. We hypothesized
      that short-acting beta2-agonist (SABA) reliever use would predict short- and long
      term exacerbation risk in COPD patients. METHODS: We performed a retrospective
      analysis of data from a study (ClinicalTrials.gov registration: NCT00419744)
      comparing budesonide/formoterol 320/9 MUg with formoterol 9 MUg (both twice
      daily) in patients with moderate-to-very-severe COPD; reliever salbutamol 90 MUg
      was provided. First occurrence of reliever use >4 (low), >10 (medium), and >20
      (high) inhalations/day was assessed as a predictor of short-term (3-week)
      exacerbation risk. Mean daily reliever use in the week preceding the 2-month
      visit was investigated as a predictor of the long-term (10-month) exacerbation
      risk, using intervals of 2-5, 6-9, and >=10 inhalations/day. RESULTS: Overall,
      810 patients were included (61 % male; mean age 63.2 years; post-bronchodilator
      forced expiratory volume in 1 s 37.7 % of predicted). First occurrence of low,
      medium, or high reliever use was predictive of an exacerbation within the
      following 3 weeks; exacerbation risk increased significantly with increasing
      reliever use. Mean reliever use over 1 week was predictive of long-term
      exacerbation risk. Patients with mean use of 2-5, 6-9, and >=10 inhalations/day
      exhibited 21 %, 67 %, and 135 % higher exacerbation rates, respectively, in the
      following 10 months, compared with <2 inhalations/day. Budesonide/formoterol was
      associated with lower short- and long-term exacerbation risk than formoterol in
      all reliever-use groups. CONCLUSIONS: SABA reliever use is a predictor of short-
      and long-term exacerbation risk in moderate-to-very-severe COPD patients with a
      history of exacerbations receiving budesonide/formoterol or formoterol.

PMID- 26293576
TI  - CD146 as an adverse prognostic factor in uterine sarcoma.
AB  - BACKGROUND: Uterine sarcoma is an aggressive malignancy with a poor prognosis.
      This study aimed to determine the expression of CD146, P53, and Ki-67 in uterine
      sarcoma and to evaluate their prognostic significance. METHODS: We
      retrospectively analyzed the prognosis and clinicopathologic features of 68
      patients with uterine sarcoma. Immunohistochemical analyses of CD146, P53, and Ki
      67 were performed in tissue samples collected from these patients and their
      relationship with prognosis was investigated. RESULTS: The 5-year overall
      survival (OS) rate was 46 %. Endometrial stromal sarcoma (ESS) patients had a
      better prognosis than leiomyosarcoma (LMS) patients, with a 2-year survival rate
      of 82 %. The membrane and cytoplasm of tumor cells exhibited CD146 overexpression
      in 8 (32 %) ESS cases, which was less than the 25 (69.4 %) cases observed in LMS
      and 2 (28.6 %) in MMMT. CD146 overexpression in the membrane and cytoplasm of
      tumor cells was closely related to lymph node metastasis (P = 0.021) and Ki-67
      overexpression (P = 0.0053); there was no significant correlation with age, tumor
      size, International Federation of Obstetrics and Gynecology stage, or P53
      overexpression in LMS. CONCLUSIONS: CD146, P53, and Ki-67 are overexpressed in
      uterine sarcoma. CD146 expression correlates with lymph node metastasis and is
      associated with poor OS in LMS; it may be a potential prognostic marker for LMS.

PMID- 26293577
TI  - Observation of risk factors, clinical manifestations and genetic characterization
      of recent Newcastle Disease Virus outbreak in West Malaysia.
AB  - BACKGROUND: Newcastle disease virus remains a constant threat in commercial
      poultry farms despite intensive vaccination programs. Outbreaks attributed to ND
      can escalate and spread across farms and states contributing to major economic
      loss in poultry farms. RESULTS: Phylogenetic analysis in our study showed that
      eleven of the samples belonged to genotype VIId. All farms were concurrently
      positive with two immunosuppressive viruses; Infectious Bursal Disease Virus
      (IBDV) and Marek's Disease Virus (MDV). Amino acid sequence analysis confirmed
      that eleven of the samples had sequence motifs for velogenic/mesogenic strains;
      three were lentogenic. CONCLUSION: In conclusion, no new NDV genotype was
      isolated from the 2011 NDV outbreak. This study suggests that the presence of
      other immunosuppressive agents such as IBD and MDV could have contributed to the
      dysfunction of the immune system of the chickens, causing severe NDV outbreaks in
      2011. Risk factors related to biosecurity and farm practices appear to have a
      significant role in the severity of the disease observed in affected farms.

PMID- 26293579
TI  - High Court rules against Birmingham University in investigation of leading
      diabetologist.

PMID- 26293578
TI  - Foxp3-modified bone marrow mesenchymal stem cells promotes liver allograft
      tolerance through the generation of regulatory T cells in rats.
AB  - BACKGROUND: The transcription factor forkhead box P3 (Foxp3) is a master
      regulatory gene necessary for the development and function of CD4(+)CD25(+)
      regulatory T cells (Tregs). Mesenchymal stem cells (MSC) have recently emerged as
      promising candidates for cell-based immunosuppression/tolerance induction
      protocols. Thus, we hypothesized that MSC-based Foxp3 gene therapy would improve
      immunosuppressive capacity of MSC and induce donor-specific allograft tolerance
      in rat's liver allograft model. METHODS: The present study utilized a lentivirus
      vector to overexpress the therapeutic gene Foxp3 on MSC. In vivo, Injections of 2
      * 10(6) MSC, FUGW-MSC or Foxp3-MSC into the portal vein were carried out
      immediately after liver transplantation. RESULTS: Successful gene transfer of
      Foxp3 in MSC was achieved by lentivirus carrying Foxp3 and Foxp3-MSC engraftment
      in liver allograft was confirmed by fluorescence microscopy. Foxp3-MSC treatment
      significantly inhibited the proliferation of allogeneic ACI CD4(+) T cells to
      splenocytes (SC) from the same donor strain or third-party BN rat compared with
      MSC. Foxp3-MSC suppressive effect on the proliferation of CD4(+) T cells is
      contact dependent and associated with Programmed death ligand 1(PD-L1)
      upregulation in MSC. Co-culture of CD4(+) T cells with Foxp3-MSC results in a
      shift towards a Tregs phenotype. More importantly, Foxp3-MSC monotherapy achieved
      donor-specific liver allograft tolerance and generated a state of
      CD4(+)CD25(+)Foxp3(+) Tregs-dependent tolerance. CONCLUSION: Foxp3-engineered MSC
      therapy seems to be a promising and attractive cell therapy approach for inducing
      immunosuppression or transplant tolerance.

PMID- 26293581
TI  - Emerging drugs in refractory colorectal cancer.
AB  - Colorectal cancer is the third leading cause of cancer-related deaths in the
      western world. Despite therapeutic advances, the prognosis of metastatic
      colorectal cancer patients remains poor due to intrinsic or acquired tumor drug
      resistance. The main mechanisms of tumor drug resistance are represented by
      genetic and epigenetic alterations. This leads to tumor refractoriness during
      treatment or disease progression following response to first-line therapy.
      Strategies to combat chemorefractory tumors involve the development of selective
      inhibitors of drug-resistant phenotypes, the epigenetic resensitization of drug
      resistant cancer cells and new cytotoxic drugs devoid of cross resistance with
      first-line cytotoxics. The use of drug combination regimens may also increase
      treatment efficacy, and the exploitation of specific phenomena such as oncogenic
      and nononcogenic addiction or synthetic lethality represents another potential
      approach in combating tumor drug resistance. Clinical trials based on such
      strategies in mCRC patients whose tumors progressed following first-line
      chemotherapy are discussed herein. 

PMID- 26293580
TI  - Attacking cancer's Achilles heel: antagonism of anti-apoptotic BCL-2 family
      members.
AB  - Malignant cells routinely violate cellular checkpoints that should initiate cell
      death in normal cells by triggering pro-apoptotic members of the BCL-2 family of
      proteins. To escape such death inducing signals, cancer cells often select for
      upregulation of anti-apoptotic BCL-2 family members including BCL-2, BCL-XL , BFL
      1, BCL-W and MCL-1. These family members prevent death by sequestering pro
      apoptotic molecules. To counter this resistance mechanism, small molecule
      inhibitors of anti-apoptotic BCL-2 family members have been under development.
      These molecules have shown promise in pre-clinical and clinical testing to
      overcome apoptotic resistance, prompting cancer cells to undergo apoptosis.
      Alternatively, other strategies have taken advantage of the normal regulatory
      machinery controlling anti-apoptotic molecules and have used inhibitors of
      signaling pathways to down-modulate the expression of anti-apoptotic molecules,
      thus tilting the balance in cancer cells to cell death. This review explores
      recent developments and strategies aimed at antagonizing anti-apoptotic BCL-2
      family member action to promote the induction of cell death in cancer therapy.

PMID- 26293582
TI  - Tranexamic acid evokes pain by modulating neuronal excitability in the spinal
      dorsal horn.
AB  - Tranexamic acid (TXA) is an antifibrinolytic agent widely used to reduce blood
      loss during surgery. However, a serious adverse effect of TXA is seizure due to
      inhibition of gamma-aminobutyric acid (GABA) and glycine receptors in cortical
      neurons. These receptors are also present in the spinal cord, and antagonism of
      these receptors in spinal dorsal horn neurons produces pain-related phenomena,
      such as allodynia and hyperalgesia, in experimental animals. Moreover, some
      patients who are injected intrathecally with TXA develop severe back pain.
      However, the effect of TXA on spinal dorsal horn neurons remain poorly
      understood. Here, we investigated the effects of TXA by using behavioral measures
      in rats and found that TXA produces behaviors indicative of spontaneous pain and
      mechanical allodynia. We then performed whole-cell patch-clamp experiments that
      showed that TXA inhibits GABAA and glycine receptors in spinal dorsal horn
      neurons. Finally, we also showed that TXA facilitates activation of the
      extracellular signal-regulated kinase in the spinal cord. These results indicated
      that TXA produces pain by inhibiting GABAA and glycine receptors in the spinal
      dorsal horn. 

PMID- 26293583
TI  - Efficacy of orally administered Silexan in patients with anxiety-related
      restlessness and disturbed sleep--A randomized, placebo-controlled trial.
AB  - The anxiolytic effect of Silexan, a patented active substance with an essential
      oil produced from Lavandula angustifolia flowers, was investigated in patients
      with anxiety-related restlessness and disturbed sleep. 170 out-patients with a
      diagnosis of restlessness (ICD-10 R45.1), a Hamilton Anxiety Scale (HAMA) total
      score >=18 points and >=2 points for HAMA items 'Tension' and 'Insomnia'
      participated in this randomized, double-blind trial and received 80mg Silexan or
      placebo once daily for 10 weeks. Patients with clinically important other
      psychiatric or neurological disorders potentially interfering with the assessment
      of treatment efficacy were excluded. Outcome variables were the HAMA as well as
      the Pittsburgh Sleep Quality Index (PSQI), the Zung Self-rating Anxiety Scale, a
      State Check inventory and the Clinical Global Impressions questionnaire. In the
      Silexan group the HAMA total score decreased from an average of 25.5+/-6.0 points
      at baseline to 13.7+/-7.0 points at treatment end, compared to a decrease from
      26.5+/-6.1 to 16.9+/-9.8 for placebo, corresponding to decreases of 12.0 and 9.3
      points (marginal means), respectively (group difference: p=0.03, ANCOVA with
      factor treatment and baseline value as covariate). In all outcome measures the
      treatment effect of Silexan was more pronounced than with placebo. According to
      the HAMA, 48.8% and 33.3% of the patients were responders (Silexan, placebo;
      reduction >=50%; p=0.04) and 31.4% and 22.6% achieved remission (HAMA<10;
      p=0.20). 33.7% (Silexan) and 35.7% (placebo) of the participants reported adverse
      events. The study confirms the calming and anxiolytic efficacy of Silexan. 

PMID- 26293584
TI  - Cognitive impairment in remitted and non-remitted depressive patients: A follow
      up comparison between first and recurrent episodes.
AB  - Cognitive impairment is a core symptom of depressive disorders associated with
      poor social function. New research is needed to analyze depression-related
      symptoms in cognitive impairment and to observe if they are reversible or not
      during clinical remission in patients with or without previous episodes. None of
      the previous studies has analyzed the differences between first and recurrent
      episodes in a long-term follow-up study related with remission state. The aim of
      our study was to compare cognitive performance and assess the impact of previous
      depressive episodes in a sample of patients in acute phase and in remission six
      month later. 79 depressive patients were assessed at baseline. The instruments
      used for clinical and cognitive assessment were: Hamilton Depression Rating
      Scale, Mini-Mental State Examination and the Clinical Global Impression Rating
      Scales, Trail Making Test parts A and B, Digital Span subtest of WAIS, Stroop
      Colour Word Test, Tower of London, Controlled Verbal Fluency Task, Semantic
      Verbal Fluency and Finger Tapping Test. A repeated measures MANCOVA with
      education as covariate was used. No differences were found at baseline between
      first episode and recurrent depressive patients. At six month, remitted patients
      scored significant better in TMT-A, TMT-B, Animals and Tower of London total
      time. Remitted first depressive patients scored significant worse than remitted
      recurrent depressive patients. The main finding of the study is the effect of
      remission on cognitive function despite previous episodes. However first episode
      remitted patients seemed to have poor access to long term memory than recurrent
      remitted patients. 

PMID- 26293585
TI  - Isolation of methicillin-resistant Staphylococcus aureus from small ruminants and
      their meat at slaughter and retail level in Greece.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) presents major health risk for
      humans causing serious nosocomial and community-acquired infections. Asymptomatic
      food-producing animal carriers and their meat may represent potential reservoirs
      for human infections. The aim of this study was to investigate the prevalence of
      MRSA in small ruminants raised under free-range conditions and their meat at
      slaughter and retail level in Northern Greece. Staphylococcus aureus was isolated
      from 9.6% of the examined samples. All isolates were resistant at least to one
      antibiotic, whereas 59.3% of them were multidrug resistant (MDR) exhibiting
      resistance to three or more antibiotic classes. The higher resistance rates were
      observed against penicillin (100%), tetracycline (74%), clindamycin (59.3%) and
      erythromycin (51.9%). Resistance to cefoxitin was exhibited by 22.2% of the
      isolates, but only one isolate was found to carry the mecA gene and belonged to
      spa type t127. This is the first time this type of Staph. aureus is isolated in
      Greece from the surface of a small ruminant's carcass. The presence of multidrug
      resistant Staph. aureus, and especially MRSA, in small ruminants and their meat,
      represents a potential threat for the spread of this pathogen in the community.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first report on
      methicillin-resistant Staphylococcus aureus in small ruminants and their meat at
      slaughter level in Greece, elucidating a possible vehicle food for transmission
      to humans. These results suggest that human or animal sources could be involved
      in meat contamination and thus sources of contamination require investigation to
      control the dispersion of MRSA in the community.

PMID- 26293586
TI  - New salivary anti-haemostatics containing protective epitopes from Ornithodoros
      moubata ticks: Assessment of their individual and combined vaccine efficacy.
AB  - Ornithodoros moubata is the main vector of the pathogens causing African swine
      fever and human relapsing fever in Africa. The development of an efficient
      vaccine against this tick would facilitate its control and the prevention of the
      diseases it transmits to a considerable extent. Previous efforts to identify
      vaccine target candidates led us to the discovery of novel salivary proteins that
      probably act as anti-haemostatics at the host-tick interface, including a
      secreted phospholipase A2 (PLA2), a 7DB-like protein (7DB-like), a riboprotein
      60S L10 (RP-60S), an apyrase (APY), and a new platelet aggregation inhibitor
      peptide, designated mougrin (MOU). In this work, the corresponding recombinant
      proteins were expressed in Escherichia coli and their individual vaccine efficacy
      was tested in rabbit vaccination trials. All of them, except the less immunogenic
      RP-60S, induced strong humoral responses that reduced tick feeding and survival,
      providing vaccine efficacies of 44.2%, 43.2% and 27.2%, 19.9% and 17.3% for PLA2,
      APY, MOU, RP-60S and 7DB-like, respectively. In the case of the more protective
      recombinant antigens (PLA2, APY and MOU), the immunodominant protective linear B
      cell epitopes were identified and their combined vaccine efficacy was tested in a
      second vaccine trial using different adjuvants. In comparison with the best
      efficacy of individual antigens, the multicomponent vaccine increased vaccine
      efficacy by 13.6%, indicating additive protective effects rather than a
      synergistic effect. Tick saliva inoculated during natural tick-host contacts had
      a boosting effect on vaccinated animals, increasing specific antibody levels and
      protection. 

PMID- 26293587
TI  - Power and conflict: the effect of a superior's interpersonal behaviour on
      trainees' ability to challenge authority during a simulated airway emergency.
AB  - A key factor that may contribute to communication failures is status asymmetry
      between team members. We examined the effect of a consultant anaesthetist's
      interpersonal behaviour on trainees' ability to effectively challenge clearly
      incorrect clinical decisions. Thirty-four trainees were recruited to participate
      in a video-recorded scenario of an airway crisis. They were randomised to a group
      in which a confederate consultant anaesthetist's interpersonal behaviour was
      scripted to recreate either a strict/exclusive or an open/inclusive communication
      dynamic. The scenario allowed trainees four opportunities to challenge clearly
      wrong decisions. Performances were scored using the modified Advocacy-Inquiry
      Score. The highest median (IQR [range]) score was 3.0 (2.2-4.0 [1.0-5.0]) in the
      exclusive communication group, and 3.5 (3.0-4.5 [2.5-6.0]) in the inclusive
      communication group (p = 0.06). The study did not show a significant effect of
      consultant behaviour on trainees' ability to challenge their superior. It did
      demonstrate trainees' inability to challenge their seniors effectively, resulting
      in critical communication gaps. 

PMID- 26293588
TI  - Epileptic encephalopathies: Optimizing seizure control and developmental outcome.
AB  - Cognitive and developmental outcomes in patients with epileptic encephalopathy
      are hypothesized to result from an interplay between the underlying epileptic
      pathologic substrate and the acquired consequences of frequent and repetitive
      seizures and epileptiform discharges that often straddle the interictal and ictal
      boundaries. This article briefly reviews the evidence related to this assumption,
      presents critical questions that need to be answered to clarify this
      relationship, and advances a set of concrete steps that may help improve
      developmental patient outcomes. 

PMID- 26293589
TI  - Zero-Determinant Strategies in Iterated Public Goods Game.
AB  - Recently, Press and Dyson have proposed a new class of probabilistic and
      conditional strategies for the two-player iterated Prisoner's Dilemma, so-called
      zero-determinant strategies. A player adopting zero-determinant strategies is
      able to pin the expected payoff of the opponents or to enforce a linear
      relationship between his own payoff and the opponents' payoff, in a unilateral
      way. This paper considers zero-determinant strategies in the iterated public
      goods game, a representative multi-player game where in each round each player
      will choose whether or not to put his tokens into a public pot, and the tokens in
      this pot are multiplied by a factor larger than one and then evenly divided among
      all players. The analytical and numerical results exhibit a similar yet different
      scenario to the case of two-player games: (i) with small number of players or a
      small multiplication factor, a player is able to unilaterally pin the expected
      total payoff of all other players; (ii) a player is able to set the ratio between
      his payoff and the total payoff of all other players, but this ratio is limited
      by an upper bound if the multiplication factor exceeds a threshold that depends
      on the number of players. 

PMID- 26293591
TI  - Extremely bulky amide ligands in main group chemistry.
AB  - The search for extremely sterically demanding monodentate amide ligands to access
      main group complexes in low-coordination numbers and highly reactive bonding
      modes is an area of intense research interest. The recent development of three
      classes of sterically demanding, monodentate amide ligands - the m-terphenyl
      anilides [N(R){C6H3Ar2-2,6}](-) (Ar = aryl, R = H, methyl, silyl), substituted
      carbazol-9-yl and the extremely bulky amides [N(R)(Ar')](-) (Ar' = 2,6-{C(H)Ph2}
      4-R'-C6H2, R = silyl, aryl, silyloxy, R' = alkyl) is facilitating the isolation
      of stable species with new coordination modes for the main group elements. These
      compounds are of fundamental importance not only from the investigation of their
      structure and bonding, but also the investigation of their reactivity highlights
      the potential for small molecule activation chemistry under mild conditions and
      applications in catalysis. This review reports on the recent developments for
      these compounds with emphasis on their synthesis, structure and reactivity. 

PMID- 26293590
TI  - Optogenetic control of cell signaling pathway through scattering skull using
      wavefront shaping.
AB  - We introduce a non-invasive approach for optogenetic regulation in biological
      cells through highly scattering skull tissue using wavefront shaping. The
      wavefront of the incident light was systematically controlled using a spatial
      light modulator in order to overcome multiple light-scattering in a mouse skull
      layer and to focus light on the target cells. We demonstrate that illumination
      with shaped waves enables spatiotemporal regulation of intracellular Ca(2+) level
      at the individual-cell level. 

PMID- 26293592
TI  - An Exploratory and Comparative Evaluation on the Spatial Perception of Two
      Densities of Multioccupancy Hospital Rooms.
AB  - OBJECTIVE: The objective of this article was to explore interior spatial
      qualifications on patient perception of two densities of multioccupancy hospital
      rooms. BACKGROUND: The research setting of this study was the three- and six
      person capacity hospital rooms used for treatment of patients at a large hospital
      in a major metropolitan city in Turkey. METHOD: The subjects used in the study
      were randomly selected from among patients treated in the surgical medical
      sciences' departments of the hospital. Accordingly, a research questionnaire was
      applied to a total of 101 subjects. RESULTS: Results have shown that the three
      person rooms were assessed more positively for privacy, functional, and
      perceptual qualifications compared to the six-person rooms. An increase in the
      number of persons and interior units of rooms affects negatively the auditory
      privacy and privacy areas of other patients. CONCLUSION: Consequently, although
      these rooms with different spatial sizes were very similar for concentration of
      persons and commodities, six-person rooms were perceived to be more crowded than
      three-person rooms.

PMID- 26293593
TI  - The relationship between alcohol consumption and menstrual cycle: a review of the
      literature.
AB  - Alcohol use affects men and women differently, with women being more affected by
      the health effects of alcohol use (NIAAA, 2011). Yet, a dearth of information
      investigating the alcohol use in women exists (SAMSHA, 2011). In particular, one
      dispositional factor hypothesized to contribute to alcohol consumption in women
      is the menstrual cycle. However, only 13 empirical papers have considered the
      menstrual cycle as related to alcohol consumption in women. These studies fall
      out with somewhat mixed findings suggesting that the premenstrual week is
      associated with increased, decreased, or no change in alcohol consumption, likely
      due to methodological differences in menstrual cycle determination and measures
      of alcohol consumption. These methodological differences and possible other
      contributing factors are discussed here with recommendations for future research
      in this area. Understanding the contribution of the menstrual cycle to alcohol
      consumption is one step in addressing an important women's health concern. 

PMID- 26293595
TI  - The Journal of Mammary Gland Biology and Neoplasia into the future - the
      potential of plasticity and pluripotency.

PMID- 26293596
TI  - Innovate, Inform, Integrate: VicHealth is transforming to meet innovation and the
      new health promotion challenges.

PMID- 26293594
TI  - Exome Sequencing of SLC30A2 Identifies Novel Loss- and Gain-of-Function Variants
      Associated with Breast Cell Dysfunction.
AB  - The zinc (Zn) transporter ZnT2 (SLC30A2) is expressed in specialized secretory
      cells including breast, pancreas and prostate, and imports Zn into mitochondria
      and vesicles. Mutations in SLC30A2 substantially reduce milk Zn concentration
      ([Zn]) and cause severe Zn deficiency in exclusively breastfed infants. Recent
      studies show that ZnT2-null mice have low milk [Zn], in addition to profound
      defects in mammary gland function during lactation. Here, we used breast milk
      [Zn] to identify novel non-synonymous ZnT2 variants in a population of lactating
      women. We also asked whether specific variants induce disturbances in
      intracellular Zn management or cause cellular dysfunction in mammary epithelial
      cells. Healthy, breastfeeding women were stratified into quartiles by milk [Zn]
      and exonic sequencing of SLC30A2 was performed. We found that 36% of women tested
      carried non-synonymous ZnT2 variants, all of whom had milk Zn levels that were
      distinctly above or below those in women without variants. We identified 12 novel
      heterozygous variants. Two variants (D(103)E and T(288)S) were identified with
      high frequency (9 and 16%, respectively) and expression of T(288)S was associated
      with a known hallmark of breast dysfunction (elevated milk sodium/potassium
      ratio). Select variants (A(28)D, K(66)N, Q(71)H, D(103)E, A(105)P, Q(137)H,
      T(288)S and T(312)K) were characterized in vitro. Compared with wild-type ZnT2,
      these variants were inappropriately localized, and most resulted in either 'loss
      of-function' or 'gain-of-function', and altered sub-cellular Zn pools, Zn
      secretion, and cell cycle check-points. Our study indicates that SLC30A2 variants
      are common in this population, dysregulate Zn management and can lead to breast
      cell dysfunction. This suggests that genetic variation in ZnT2 could be an
      important modifier of infant growth/development and reproductive health/disease.
      Importantly, milk [Zn] level may serve as a bio-reporter of breast function
      during lactation.

PMID- 26293597
TI  - Evolutionary developmental pathology and anthropology: A new field linking
      development, comparative anatomy, human evolution, morphological variations and
      defects, and medicine.
AB  - We introduce a new subfield of the recently created field of Evolutionary
      Developmental-Anthropology (Evo-Devo-Anth): Evolutionary-Developmental-Pathology
      and-Anthropology (Evo-Devo-P'Anth). This subfield combines experimental and
      developmental studies of nonhuman model organisms, biological anthropology,
      chordate comparative anatomy and evolution, and the study of normal and
      pathological human development. Instead of focusing on other organisms to try to
      better understand human development, evolution, anatomy, and pathology, it places
      humans as the central case study, i.e., as truly model organism themselves. We
      summarize the results of our recent Evo-Devo-P'Anth studies and discuss long
      standing questions in each of the broader biological fields combined in this
      subfield, paying special attention to the links between: (1) Human anomalies and
      variations, nonpentadactyly, homeotic transformations, and "nearest neighbor" vs.
      "find and seek" muscle-skeleton associations in limb+facial muscles vs. other
      head muscles; (2) Developmental constraints, the notion of "phylotypic stage,"
      internalism vs. externalism, and the "logic of monsters" vs. "lack of
      homeostasis" views about human birth defects; (3) Human evolution, reversions,
      atavisms, paedomorphosis, and peromorphosis; (4) Scala naturae, Haeckelian
      recapitulation, von Baer's laws, and parallelism between phylogeny and
      development, here formally defined as "Phylo-Devo parallelism"; and (5) Patau,
      Edwards, and Down syndrome (trisomies 13, 18, 21), atavisms, apoptosis, heart
      malformations, and medical implications.

PMID- 26293598
TI  - Solution NMR Experiment for Measurement of (15)N-(1)H Residual Dipolar Couplings
      in Large Proteins and Supramolecular Complexes.
AB  - NMR residual dipolar couplings (RDCs) are exquisite probes of protein structure
      and dynamics. A new solution NMR experiment named 2D SE2 J-TROSY is presented to
      measure N-H RDCs for proteins and supramolecular complexes in excess of 200 kDa.
      This enables validation and refinement of their X-ray crystal and solution NMR
      structures and the characterization of structural and dynamic changes occurring
      upon complex formation. Accurate N-H RDCs were measured at 750 MHz (1)H resonance
      frequency for 11-mer 93 kDa (2)H,(15)N-labeled Trp RNA-binding attenuator protein
      tumbling with a correlation time tauc of 120 ns. This is about twice as long as
      that for the most slowly tumbling system, for which N-H RDCs could be measured,
      so far, and corresponds to molecular weights of ~200 kDa at 25  degrees C.
      Furthermore, due to the robustness of SE2 J-TROSY with respect to residual (1)H
      density from exchangeable protons, increased sensitivity at (1)H resonance
      frequencies around 1 GHz promises to enable N-H RDC measurement for even larger
      systems. 

PMID- 26293600
TI  - Gastrointestinal stromal tumor presenting as gastroduodenal intussusception.

PMID- 26293599
TI  - KANSL1 gene disruption associated with the full clinical spectrum of 17q21.31
      microdeletion syndrome.
AB  - BACKGROUND: Chromosome 17q21.31 microdeletion syndrome is a multisystem genomic
      disorder caused by a recurrent 600-kb-long deletion, or haploinsufficiency of the
      chromatin modifier gene KANSL1, which maps to that region. Patients with KANSL1
      intragenic mutations have been reported to display the major clinical features of
      17q21.31 microdeletion syndrome. However, they did not exhibit the full clinical
      spectrum of this disorder, which might indicate that an additional gene or genes,
      located in the 17q21.31 locus, might also be involved in the syndrome's
      phenotype. METHODS: Conventional and molecular karyotypes were performed on a
      female patient with intellectual disability, agenesis of the corpus callosum,
      heart defects, hydronephrosis, hypotonia, pigmentary skin anomalies and facial
      dysmorphic features. FISH analysis was conducted for chromosomal breakpoint
      localization. qRT-PCR was applied for the comparative gene expression of KANSL1
      gene in the patient and a control group. RESULTS: Herein, we present the first
      report of disruption and haploinsufficiency of the KANSL1 gene, secondary to a
      t(1;17)(q12;q21)dn chromosomal translocation in a girl that also carried a de
      novo ~289-kb deletion on 16p11.2. KANSL1 gene expression studies and comparative
      clinical analysis of patients with 17q21.31 deletions and intragenic KANSL1 gene
      defects indicate that KANSL1 dysfunction is associated with the full spectrum of
      the 17q21.31 microdeletion syndrome, which includes characteristic facial
      features, hypotonia, intellectual disability, and structural defects of the
      brain, heart and genitourinary system, as well as, musculoskeletal and
      neuroectodermal anomalies. Moreover, we provide further evidence for the
      overlapping clinical phenotype of this condition with the cardio-facio-cutaneous
      (CFC) syndrome. CONCLUSIONS: KANSL1 gene haploinsufficiency is necessary and
      sufficient to cause the full spectrum of the 17q21.31 microdeletion syndrome. We
      hypothesize that the KANSL1 gene might have an effect on the Ras/mitogen
      activated protein kinase (MAPK) pathway activity, which is known to be
      deregulated in the CFC syndrome. This pathway has a crucial role in the
      development of the heart and craniofacial morphology, as well as the skin, eye,
      brain and musculoskeletal systems.

PMID- 26293601
TI  - [Sonographic fracture diagnostics].
AB  - BACKGROUND: In clinically suspected fractures taking radiographs is the standard
      procedure but the indications should be strictly limited. Ultrasound offers a
      safe and radiation-free alternative for fracture diagnostics. OBJECTIVES:
      Sensitivity and specificity of sonographic fracture diagnostics and safety of
      sonographic algorithms for fracture evaluation. METHODS: Presentation of useful
      applications for sonographic fracture evaluation and establishment of sonographic
      algorithms for safe fracture diagnosis. RESULTS: In children distal forearm
      fractures can be diagnosed solely by ultrasound (sensitivity 96 % and specificity
      97 %). The sonographic fat pad sign (SOFA) has been proven to be a useful primary
      screening tool for occult fractures of the pediatric elbow. A positive fat pad
      sign (SOFA+) is indicative of a fracture and radiographic diagnostics are
      necessary (sensitivity 97 % and specificity 91 %). Ultrasonography is also useful
      to exclude subcapital humeral fractures (sensitivity 94 % and specificity 100 %)
      and for correct estimation of displacement when present. CONCLUSIONS: Sonographic
      algorithms for fracture evaluation (SAFE) offer a safe diagnosis and guidance of
      the therapeutic course of certain pediatric fractures, thereby reducing
      unnecessary radiation exposure.

PMID- 26293602
TI  - [Diffusion-weighted imaging and diffusion tensor imaging in preoperative
      diagnostics].
AB  - The extent of anisotropy and the direction of diffusion of H protons characterize
      the tissue structure and qualitative and quantitative evaluation of the
      appropriate parameters provide inferences for the membrane permeability, axon
      thickness, integrity and connectivity. The technique of fiber tracking is
      implemented in the presurgical diagnostics for lesions in the brain to show the
      relationship of the lesion to the fiber system. The benefit of this technique for
      preoperative and intraoperative localization of the pyramidal tracts, the primary
      motor areas, the optic radiation and the speech regions could be confirmed. In
      focal gliomas the fibers are often displaced to the edge of the tumor; however,
      in diffusely growing tumors the fiber system is infiltrated by tumor cells. In
      high-grade gliomas destruction of the fibers often occurs. Limitations are always
      present in brain regions where several fiber systems cross in different
      directions, such as the centrum semiovale. Appropriate neuroanatomical knowledge
      must be present in order to be able to immediately recognize such possible
      deviant pathways of the fiber tracking. 

PMID- 26293603
TI  - Can functional hologenomics aid tackling current challenges in plant breeding?
AB  - Molecular plant breeding usually overlooks the genetic variability that arises
      from the association of plants with endophytic microorganisms, when looking at
      agronomic interesting target traits. This source of variability can have crucial
      effects on the functionality of the organism considered as a whole (the
      holobiont), and therefore can be selectable in breeding programs. However, seeing
      the holobiont as a unit for selection and improvement in breeding programs
      requires novel approaches for genotyping and phenotyping. These should not focus
      just at the plant level, but also include the associated endophytes and their
      functional effects on the plant, to make effective desirable trait screenings.
      The present review intends to draw attention to a new research field on
      functional hologenomics that if associated with adequate phenotyping tools could
      greatly increase the efficiency of breeding programs. 

PMID- 26293604
TI  - Toward understanding the evolution of vertebrate gene regulatory networks:
      comparative genomics and epigenomic approaches.
AB  - Vertebrates, as most animal phyla, originated >500 million years ago during the
      Cambrian explosion, and progressively radiated into the extant classes. Inferring
      the evolutionary history of the group requires understanding the architecture of
      the developmental programs that constrain the vertebrate anatomy. Here, I review
      recent comparative genomic and epigenomic studies, based on ChIP-seq and
      chromatin accessibility, which focus on the identification of functionally
      equivalent cis-regulatory modules among species. This pioneer work, primarily
      centered in the mammalian lineage, has set the groundwork for further studies in
      representative vertebrate and chordate species. Mapping of active regulatory
      regions across lineages will shed new light on the evolutionary forces
      stabilizing ancestral developmental programs, as well as allowing their variation
      to sustain morphological adaptations on the inherited vertebrate body plan. 

PMID- 26293605
TI  - Satellite non-coding RNAs: the emerging players in cells, cellular pathways and
      cancer.
AB  - For several decades, transcriptional inactivity was considered as one of the
      particular features of constitutive heterochromatin and, therefore, of its major
      component, satellite DNA sequences. However, more recently, succeeding evidences
      have demonstrated that these sequences can indeed be transcribed, yielding
      satellite non-coding RNAs with important roles in the organization and regulation
      of genomes. Since then, several studies have been conducted, trying to understand
      the function(s) of these sequences not only in the normal but also in cancer
      genomes. It is thought that the association between cancer and satncRNAs is
      mostly due to the influence of these transcripts in the genome instability, a
      hallmark of cancer. The few reports on satellite DNA transcription in cancer
      contexts point to its overexpression; however, this scenario may be far more
      complex, variable, and influenced by a number of factors and the exact role of
      satncRNAs in the oncogenic process remains poorly understood. The greater is the
      knowledge on the association of satncRNAs with cancer, the greater would be the
      opportunity to assist cancer treatment, either by the design of effective
      therapies targeting these molecules or by using them as biomarkers in cancer
      diagnosis, prognosis, and with predictive value.

PMID- 26293607
TI  - Chimeric peptide constructs comprising linear B-cell epitopes: application to the
      serodiagnosis of infectious diseases.
AB  - Linear B-cell epitopes are ideal biomarkers for the serodiagnosis of infectious
      diseases. However, the long-predicted diagnostic value of epitopes has not been
      realized. Here, we demonstrated a method, diagnostic epitopes in four steps
      (DEIFS), that delivers a combination of epitopes for the serodiagnosis of
      infectious diseases with a high success rate. Using DEIFS for malaria, we
      identified 6 epitopes from 8 peptides and combined them into 3 chimeric peptide
      constructs. Along with 4 other peptides, we developed a rapid diagnostic test
      (RDT), which is able to differentiate Plasmodium falciparum (P. falciparum) from
      Plasmodium vivax (P. vivax) infections with 95.6% overall sensitivity and 99.1%
      overall specificity. In addition to applications in diagnosis, DEIFS could also
      be used in the diagnosis of virus and bacterium infections, discovery of vaccine
      candidates, evaluation of vaccine potency, and study of disease progression. 

PMID- 26293606
TI  - Structural and functional liaisons between transposable elements and satellite
      DNAs.
AB  - Transposable elements (TEs) and satellite DNAs (satDNAs) are typically identified
      as major repetitive DNA components in eukaryotic genomes. TEs are DNA segments
      able to move throughout a genome while satDNAs are tandemly repeated sequences
      organized in long arrays. Both classes of repetitive sequences are extremely
      diverse, and many TEs and satDNAs exist within a genome. Although they differ in
      structure, genomic organization, mechanisms of spread, and evolutionary dynamics,
      TEs and satDNAs can share sequence similarity and organizational patterns, thus
      indicating that complex mutual relationships can determine their evolution, and
      ultimately define roles they might have on genome architecture and function.
      Motivated by accumulating data about sequence elements that incorporate features
      of both TEs and satDNAs, here we present an overview of their structural and
      functional liaisons. 

PMID- 26293608
TI  - Can the cardiovascular family history reported by our patients be trusted? The
      Norwegian Stroke in the Young Study.
AB  - BACKGROUND AND PURPOSE: Family history (FH) is used as a marker for inherited
      risk. Using FH for this purpose requires the FH to reflect true disease in the
      family. The aim was to analyse the concordance between young and middle-aged
      ischaemic stroke patients' reported FH of cardiovascular disease (CVD) with their
      parents' own reports. METHODS: Ischaemic stroke patients aged 15-60 years and
      their eligible parents were interviewed using a standardized questionnaire.
      Information of own CVD and FH of CVD was registered. Concordance between patients
      and parents was tested by kappa statistics, sensitivity, specificity, predictive
      values and likelihood ratios. Regression analyses were performed to identify
      patient characteristics associated with non-concordance of replies. RESULTS:
      There was no difference in response rate between fathers and mothers (P = 0.355).
      Both parents responded in 57 cases. Concordance between patient and parent
      reports was good, with kappa values ranging from 0.57 to 0.7. The patient
      reported FH yielded positive predictive values of 75% or above and negative
      predictive values of 90% or higher. The positive likelihood ratios (LR+) were 10
      or higher and negative likelihood ratios (LR-) were generally 0.5 or lower.
      Interpretation regarding peripheral arterial disease was limited due to low
      parental prevalence. Higher age was associated with impaired concordance between
      patient and parent reports (odds ratio 1.05; 95% confidence interval 1.01-1.09; P
      = 0.020). CONCLUSIONS: The FH provided by young and middle-aged stroke patients
      is in good concordance with parental reports. FH is an adequate proxy to assess
      inherited risk of CVD in young stroke patients.

PMID- 26293609
TI  - Antibacterial and anti-biofilm activity of mouthrinses containing cetylpyridinium
      chloride and sodium fluoride.
AB  - BACKGROUND: Cetylpyridinium chloride (CPC) and sodium fluoride augment oral
      hygiene by inactivating bacteria and inhibiting enamel demineralisation,
      respectively. However, there are few reports in the literature documenting the
      antibacterial efficacy of their combined use in mouthrinses. We have used six
      experimental systems to compare the antibacterial effects of mouthrinses
      containing 0.075% CPC (test rinse, TR) or 0.075% CPC with sodium fluoride (test
      fluoride rinse, TFR). RESULTS: Effects against planktonic bacteria were
      determined using viable counting (for Streptococcus mutans and salivary
      bacteria), a redox dye (for Actinomyces viscosus and salivary bacteria) and
      viable counting (for ex vivo oral rinses). Effects against saliva-derived
      biofilms were quantified using confocal microscopy and differential viable
      counting. Inhibition of biofilm formation was evaluated by pre-treating
      hydroxyapatite coupons with mouthrinses prior to inoculation. Otherwise-identical
      controls without CPC (control rinse and control fluoride rinse, CR and CFR,
      respectively), were included throughout. Compared to the controls, TFR and TR
      demonstrated significant antimicrobial effects in the redox assays, by viable
      counts (>3 log reductions) and in oral rinse samples (>1.25 log reductions, p <
      0.05). TFR and TR also significantly reduced the viability of oral biofilms. Pre
      treatment of hydroxyapatite with TFR and TR significantly inhibited biofilm
      formation (>3 log difference, p < 0.05). Overall, there were no consistent
      differences in the activities of TR and TFR. CONCLUSIONS: Sodium fluoride did not
      influence the antibacterial and anti-biofilm potency of CPC-containing
      formulations, supporting the combined use of CPC and sodium fluoride in
      mouthrinses to control oral bacteria and protect tooth enamel.

PMID- 26293610
TI  - MicroRNA-142-3p and microRNA-142-5p are downregulated in hepatocellular carcinoma
      and exhibit synergistic effects on cell motility.
AB  - MicroRNAs (miRNAs), an important class of small non-coding RNAs, regulate gene
      expression at the post-transcriptional level. miRNAs are involved in a wide range
      of biological processes and implicated in different diseases, including cancers.
      In this study, miRNA profiling and qRT-PCR validation revealed that miR-142-3p
      and miR-142-5p were significantly downregulated in hepatocellular carcinoma (HCC)
      and their expression levels decreased as the disease progressed. The ectopic
      expression of miR-142 significantly reduced HCC cell migration and invasion.
      Overexpression of either miR-142-3p or miR-142-5p suppressed HCC cell migration,
      and overexpression of both synergistically inhibited cell migration, which
      indicated that miR-142-3p and miR-142-5p may cooperatively regulate cell
      movement. miR-142-3p and miR-142-5p, which are mature miRNAs derived from the 3'-
      and 5'-strands of the precursor miR-142, target distinct pools of genes because
      of their different seed sequences. Pathway enrichment analysis showed a strong
      association of the putative gene targets of miR-142-3p and miR-142-5p with
      several cell motility-associated pathways, including those regulating actin
      cytoskeleton, adherens junctions, and focal adhesion. Importantly, a number of
      the putative gene targets were also significantly upregulated in human HCC cells.
      Moreover, overexpression of miR-142 significantly abrogated stress fiber
      formation in HCC cells and led to cell shrinkage. This study shows that mature
      miR-142 pairs collaboratively regulate different components of distinct signaling
      cascades and therefore affects the motility of HCC cells. 

PMID- 26293611
TI  - Corrigendum: Programmed cell death 5 mediates HDAC3 decay to promote genotoxic
      stress response.

PMID- 26293612
TI  - Antiplatelet therapy in acute coronary syndromes.
AB  - INTRODUCTION: Coronary thrombosis is a frequent cause of death and myocardial
      infarction most often explained by superimposition of a platelet-rich thrombus on
      existing coronary artery disease. Therefore, antiplatelet drugs are essential in
      the treatment and secondary prevention of acute coronary syndromes (ACS) and
      during percutaneous coronary intervention. Several novel antiplatelet drugs are
      now available. AREAS COVERED: For several years, aspirin and clopidogrel remained
      the cornerstone of treatment for ACS. However, prasugrel and ticagrelor have a
      more consistent, faster-acting and more potent antiplatelet effect than
      clopidogrel, which translates into improved clinical outcomes, although at the
      expense of an increased bleeding risk. Importantly, some patients experience
      cardiovascular events despite current antiplatelet treatment, because platelet
      activation may occur via pathways not inhibited by these agents. Therefore,
      improved antiplatelet strategies are warranted. EXPERT OPINION: Despite
      undisputable benefits of current antiplatelet strategies, a considerable number
      of patients continue to experience adverse thrombotic events, although clinical
      outcomes have been improved with new oral P2Y12 antagonists. New drugs have been
      developed, including intravenous P2Y12 antagonists and oral antagonist targeting
      the protease-activated receptor-1 platelet activation pathway stimulated by
      thrombin. This review provides an overview of current and novel antiplatelet
      strategies and also discusses unmet needs related to antiplatelet therapy for
      ACS.

PMID- 26293613
TI  - T-cell prolymphocytic leukemia: survival improves with alemtuzemab, but stem cell
      transplant eligibility 'counts' even more.

PMID- 26293614
TI  - Contact activation of C3 enables tethering between activated platelets and
      polymorphonuclear leukocytes via CD11b/CD18.
AB  - Complement component C3 has a potential role in thrombotic pathologies. It is
      transformed, without proteolytic cleavage, into C3(H2O) upon binding to the
      surface of activated platelets. We hypothesise that C3(H2O) bound to activated
      platelets and to platelet-derived microparticles (PMPs) contributes to platelet
      PMN complex (PPC) formation and to the binding of PMPs to PMNs. PAR-1 activation
      of platelets in human whole blood from normal individuals induced the formation
      of CD16+/CD42a+ PPC. The complement inhibitor compstatin and a C5a receptor
      antagonist inhibited PPC formation by 50 %, while monoclonal antibodies to
      C3(H2O) or anti-CD11b inhibited PPC formation by 75-100 %. Using plasma protein
      depleted blood and blood from a C3-deficient patient, we corroborated the
      dependence on C3, obtaining similar results after reconstitution with purified
      C3. By analogy with platelets, PMPs isolated from human serum were found to
      expose C3(H2O) and bind to PMNs. This interaction was also blocked by the anti
      C3(H2O) and anti-CD11b monoclonal antibodies, indicating that C3(H2O) and CD11b
      are involved in tethering PMPs to PMNs. We confirmed the direct interaction
      between C3(H2O) and CD11b by quartz crystal microbalance analysis using purified
      native C3 and recombinant CD11b/CD18 and by flow cytometry using PMP and
      recombinant CD11b. Transfectants expressing CD11b/CD18 were also shown to
      specifically adhere to surface-bound C3(H2O). We have identified contact
      activated C3(H2O) as a novel ligand for CD11b/CD18 that mediates PPC formation
      and the binding of PMPs to PMNs. Given the various roles of C3 in thrombotic
      reactions, this finding is likely to have important pathophysiological
      implications. 

PMID- 26293615
TI  - Coupling Oxygen Consumption with Hydrocarbon Oxidation in Bacterial
      Multicomponent Monooxygenases.
AB  - A fundamental goal in catalysis is the coupling of multiple reactions to yield a
      desired product. Enzymes have evolved elegant approaches to address this grand
      challenge. A salient example is the biological conversion of methane to methanol
      catalyzed by soluble methane monooxygenase (sMMO), a member of the bacterial
      multicomponent monooxygenase (BMM) superfamily. sMMO is a dynamic protein complex
      of three components: a hydroxylase, a reductase, and a regulatory protein. The
      active site, a carboxylate-rich non-heme diiron center, is buried inside the 251
      kDa hydroxylase component. The enzyme processes four substrates: O2, protons,
      electrons, and methane. To couple O2 activation to methane oxidation, timely
      control of substrate access to the active site is critical. Recent studies of
      sMMO, as well as its homologues in the BMM superfamily, have begun to unravel the
      mechanism. The emerging and unifying picture reveals that each substrate gains
      access to the active site along a specific pathway through the hydroxylase.
      Electrons and protons are delivered via a three-amino-acid pore located adjacent
      to the diiron center; O2 migrates via a series of hydrophobic cavities; and
      hydrocarbon substrates reach the active site through a channel or linked set of
      cavities. The gating of these pathways mediates entry of each substrate to the
      diiron active site in a timed sequence and is coordinated by dynamic interactions
      with the other component proteins. The result is coupling of dioxygen consumption
      with hydrocarbon oxidation, avoiding unproductive oxidation of the reductant
      rather than the desired hydrocarbon. To initiate catalysis, the reductase
      delivers two electrons to the diiron(III) center by binding over the pore of the
      hydroxylase. The regulatory component then displaces the reductase, docking onto
      the same surface of the hydroxylase. Formation of the hydroxylase-regulatory
      component complex (i) induces conformational changes of pore residues that may
      bring protons to the active site; (ii) connects hydrophobic cavities in the
      hydroxylase leading from the exterior to the diiron active site, providing a
      pathway for O2 and methane, in the case of sMMO, to the reduced diiron center for
      O2 activation and substrate hydroxylation; (iii) closes the pore, as well as a
      channel in the case of four-component BMM enzymes, restricting proton access to
      the diiron center during formation of "Fe2O2" intermediates required for
      hydrocarbon oxidation; and (iv) inhibits undesired electron transfer to the Fe2O2
      intermediates by blocking reductase binding during O2 activation. This mechanism
      is quite different from that adopted by cytochromes P450, a large class of heme
      containing monooxygenases that catalyze reactions very similar to those catalyzed
      by the BMM enzymes. Understanding the timed enzyme control of substrate access
      has implications for designing artificial catalysts. To achieve multiple
      turnovers and tight coupling, synthetic models must also control substrate
      access, a major challenge considering that nature requires large, multimeric,
      dynamic protein complexes to accomplish this feat. 

PMID- 26293616
TI  - Population Pharmacokinetic Modeling of Canagliflozin in Healthy Volunteers and
      Patients with Type 2 Diabetes Mellitus.
AB  - BACKGROUND AND OBJECTIVES: Canagliflozin is an orally active, reversible,
      selective sodium-glucose co-transporter-2 inhibitor. A population pharmacokinetic
      (popPK) model of canagliflozin, including relevant covariates as sources of inter
      individual variability, was developed to describe phase I, II, and III data in
      healthy volunteers and in patients with type 2 diabetes mellitus (T2DM). METHODS:
      The final analysis included 9061 pharmacokinetic (PK) samples from 1616
      volunteers enrolled in nine phase I, two phase II, and three phase III studies
      and was performed using NONMEM((r)) 7.1. Inter-individual variability was
      evaluated using an exponential model and the residual error model was additive in
      the log domain. The first-order conditional estimation method with interaction
      was applied and the model was parameterized in terms of rate constants. Covariate
      effects were explored graphically on empirical Bayes estimates of PK parameters,
      as shrinkage was low. Clinical relevance of statistically significant covariates
      was evaluated. The predictive properties of the model were illustrated by
      prediction-corrected visual predictive checks. RESULTS: A two-compartment PK
      model with lag-time and sequential zero- and first-order absorption and first
      order elimination best described the observed data. Sex, age, and weight on
      apparent volume of distribution of the central compartment, body mass index on
      first-order absorption rate constant, and body mass index and over-encapsulation
      on lag-time, and estimated glomerular filtration rate (eGFR, by MDRD equation),
      dose, and genetic polymorphism (carriers of UGT1A9*3 allele) on elimination rate
      constant were identified as statistically significant covariates. The prediction
      corrected visual predictive checks revealed acceptable predictive performance of
      the model. CONCLUSION: The popPK model adequately described canagliflozin PK in
      healthy volunteers and in patients with T2DM. Because of the small magnitude of
      statistically significant covariates, they were not considered clinically
      relevant. However, dosage adjustments are recommended for T2DM patients with
      renal impairment (eGFR >=60 mL/min/1.73 m(2): 100 or 300 mg/day; eGFR of 45 to
      <60 mL/min/1.73 m(2): 100 mg/day).

PMID- 26293617
TI  - Reliability of In Vitro and In Vivo Methods for Predicting the Effect of P
      Glycoprotein on the Delivery of Antidepressants to the Brain.
AB  - As the effect of P-glycoprotein (P-gp) transport on antidepressant delivery has
      been extensively evaluated using in vitro cellular and in vivo rodent models, an
      increasing number of publications have addressed the effect of P-gp in limiting
      brain penetration of antidepressants and causing treatment-resistant depression
      in current clinical therapies. However, contradictory results have been observed
      in different systems. It is of vital importance to understand the potential for
      drug interactions related to P-gp at the blood-brain barrier (BBB), and whether
      coadministration of a P-gp inhibitor together with an antidepressant is a good
      clinical strategy for dosing of patients with treatment-resistant depression. In
      this review, the complicated construction of the BBB, the transport mechanisms
      for compounds that cross the BBB, and the basic characteristics of
      antidepressants are illustrated. Further, the reliability of different systems
      related to antidepressant brain delivery, including in vitro bidirectional
      transport cell lines, in vivo Mdr1 knockout mice, and chemical inhibition studies
      in rodents are analyzed, supporting a low possibility that P-gp affects currently
      marketed antidepressants when these results are extrapolated to the human BBB.
      These findings can also be applied to other central nervous system drugs. 

PMID- 26293619
TI  - Immunoscoring by correlating MHC class II and TCR expression: high level immune
      functions represented by the KIRP dataset of TCGA.
AB  - The Cancer Genome Atlas (TCGA) is primarily oriented towards revealing the status
      of cancer cells but TCGA RNASeq data have the potential of representing gene
      expression for a variety of cells that are included during RNA preparation, i.e.,
      cells that cannot be removed from the microenvironment during cancer sample
      isolation. Thus, we seek to determine whether RNASeq data can be used to pioneer
      greater precision for immunoscoring. We obtained the RNASeq results for HLA class
      II genes, the class II transactivator (CIITA) and T-cell receptor (TCR) alpha
      segments. The data indicated strong degrees of correlation of HLA class II
      expression with TCR expression. Furthermore, biomarkers of professional antigen
      presenting cells also correlated with TCR expression, with the kidney renal
      papillary cell carcinoma (KIRP) dataset indicative of the highest level, immune
      function microenvironment. These analyses indicate that an immune function
      signature, with probable internal HLA class II-TCR verifications, can be obtained
      from individual TCGA samples; this in turn indicates that such signatures might
      provide a basis for correlations with prognosis or for convenient indications of
      therapy options, such as tumor-infiltrating lymphocyte availability for ex-vivo
      amplification. Although tumor immunoscoring has been proposed, the above analysis
      represents the first immunoscoring approach that correlates antigen presentation
      capacity with TCR mRNA expression. 

PMID- 26293620
TI  - Docetaxel-Loaded Fluorescent Liquid-Crystalline Nanoparticles for Cancer
      Theranostics.
AB  - Here, we describe a novel monoolein-based cubosome formulation engineered for
      possible theranostic applications in oncology. The Docetaxel-loaded nanoparticles
      were stabilized in water by a mixture of commercial Pluronic (poly(ethylene
      oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer) F108
      (PF108) and rhodamine- and folate-conjugated PF108 so that the nanoparticles
      possess targeting, therapeutic, and imaging properties. Nanoparticles were
      investigated by DLS, cryo-TEM, and SAXS to confirm their structural features. The
      fluorescent emission characterization of the proposed formulation indicated that
      the rhodamine conjugated to the PF108 experiences an environment less polar than
      water (similar to chloroform), suggesting that the fluorescent fragment is buried
      within the poly(ethylene oxide) corona surrounding the nanoparticle. Furthermore,
      these nanoparticles were successfully used to image living HeLa cells and
      demonstrated a significant short-term (4 h incubation) cytotoxicity effect
      against these cancer cells. Furthermore, given their analogy as nanocarriers for
      molecules of pharmaceutical interest and to better stress the singularities of
      these bicontinuous cubic nanoparticles, we also quantitatively evaluated the
      differences between cubosomes and multilamellar liposomes in terms of surface
      area and hydrophobic volume. 

PMID- 26293618
TI  - Pharmacokinetic Properties of Anticancer Agents for the Treatment of Central
      Nervous System Tumors: Update of the Literature.
AB  - Despite significant improvement in outcomes for patients with hematologic
      malignancies and solid tumors over the past 10 years, patients with primary or
      metastatic brain tumors continue to have a poor prognosis. A primary reason for
      this is the inability of many chemotherapeutic drugs to penetrate into the brain
      and brain tumors at concentrations high enough to exert an antitumor effect
      because of unique barriers and efflux transporters. Several studies have been
      published recently examining the central nervous system pharmacokinetics of
      various anticancer drugs in patients with primary and metastatic brain tumors. To
      summarize recent advances in the field, this review critically presents studies
      published within the last 9 years examining brain and cerebrospinal fluid
      penetration of clinically available anticancer agents for patients with central
      nervous system tumors. 

PMID- 26293621
TI  - High frequency of mismatch repair deficiency among pediatric high grade gliomas
      in Jordan.
AB  - Biallelic mismatch repair deficiency (bMMRD) is a cancer predisposition syndrome
      affecting primarily individuals from consanguinous families resulting in multiple
      childhood cancers including high grade gliomas (HGG). This is the first study to
      assess the prevalence of bMMRD among patients with HGG in countries where
      consanguinity is high. We collected molecular and clinical information on all
      children diagnosed with HGG and supratentorial primitive neuroectodermal tumors
      (sPNET) between 2003 and 2013 at King Hussein Cancer Center, Jordan. Comparison
      was made to a similar cohort from Toronto. Clinical data regarding presence of
      cafe au lait macules(CAL), family history of cancer, consanguinity, pathology and
      treatment were collected. Tumors were centrally reviewed and tested for MMRD by
      immunohistochemistry of the corresponding proteins. Forty-two patients fulfilled
      the inclusion criteria, including 36 with HGG. MMRD was observed in 39% of HGG of
      whom 79% also lost MMR staining in the corresponding normal cells suggestive of
      bMMRD. P53 dysfunction was highly enriched in MMR deficient tumors (p =
      0.0003).The frequency of MMRD was significantly lower in Toronto cohort (23%, p =
      0.03). Both evidence of CAL and consanguinity correlated with bMMRD (p = 0.005
      and 0.05,respectively) but family history of cancer didn't. HGG with all three
      bMMRD risk factors had evidence of MMRD and all children affected by multiple
      bMMRD related cancers had identical gene loss by immunohistochemical staining. In
      Jordan, the frequency of clinical and immunohistochemical alterations suggestive
      of bMMRD in pediatric HGG is high. Genetic testing will enable appropriate
      counseling and cancer screening to improve survival of these patients.

PMID- 26293622
TI  - Clinical Correlates of Posterior Reversible Encephalopathy Syndrome in Pregnancy.
AB  - The authors aimed to determine whether clinical findings of preeclampsia predict
      magnetic resonance imaging (MRI) diagnosis of posterior reversible encephalopathy
      syndrome (PRES). The course among preeclamptics/eclamptics with clinically
      suspected PRES with vs without MRI diagnosis of PRES was compared. Of 46 patients
      who underwent MRI (eight eclamptics, 38 preeclamptics), five eclamptics (62.5%)
      and four preeclamptics (10.5%) had confirmed PRES (P=.004). Patients with PRES
      were younger (26 years vs 31 years, P=.008) and had a higher prevalence of
      thrombocytopenia (33% vs 8%, P=.04), a greater prevalence of proteinuria (100% vs
      61%, P=.04), and higher peak systolic and diastolic blood pressures (P<.05). As
      opposed to findings from previous reports, PRES was not seen uniformly among
      eclamptic women and was found in 10.5% of preeclamptics with clinical suspicion
      of PRES in this study. Given that no single or set of findings were reliable
      predictors of PRES, consideration for rigorous management of hypertension should
      be applied to all patients with preeclampsia and eclampsia.

PMID- 26293623
TI  - First detection of the presence of naturally occurring grapevine downy mildew in
      the field by a fluorescence-based method.
AB  - Early detection of fungal pathogen presence in the field would help to better
      time or avoid some of the fungicide treatments used to prevent crop production
      losses. We recently introduced a new phytoalexin-based method for a non-invasive
      detection of crop diseases using their fluorescence. The causal agent of
      grapevine downy mildew, Plasmopara viticola, induces the synthesis of stilbenoid
      phytoalexins by the host, Vitis vinifera, early upon infection. These stilbenoids
      emit violet-blue fluorescence under UV light. A hand-held solid-state UV-LED
      based field fluorimeter, named Multiplex 330, was used to measure stilbenoid
      phytoalexins in a vineyard. It allowed us to non-destructively detect and monitor
      the naturally occurring downy mildew infections on leaves in the field. 

PMID- 26293624
TI  - Cost comparison of two implantable cardiac monitors in two different settings:
      Reveal XT in a catheterization laboratory vs. Reveal LINQ in a procedure room.
AB  - AIMS: Implantable cardiac monitors (ICMs) are used for long-term heart rhythm
      monitoring, e.g. to diagnose unexplained syncope or for detection of suspected
      atrial and ventricular arrhythmias. The newest ICM, Reveal LINQTM (Medtronic
      Inc.), is miniaturized and inserted with a specific insertion tool kit. The
      procedure is therefore minimally invasive and can be moved from catheterization
      laboratory (cath lab) to a less resource intensive setting. This study aims to
      assess the change in procedure costs when performed outside the cath lab. METHODS
      AND RESULTS: A bottom-up costing methodology was used. Data were collected from
      interviews with physicians, cath lab managers, and financial controllers.
      Hospitals in the Netherlands, France, and the UK were included in this study. The
      cost comparison of a Reveal XT implantation in a cath lab setting vs. a Reveal
      LINQ insertion outside a cath lab resulted in an estimated reduction of ?662 for
      the UK, ?682 for the Netherlands, and ?781 for France. These cost savings were
      primarily realized through fewer staff, less equipment, and overhead costs. The
      net effect on savings depends on the price differential between these two
      technologies. The patient care pathway can be improved due to the possibility to
      move the procedure out of the cath lab. CONCLUSION: Inserting the miniaturized
      version of the ICM is simpler and faster, and the procedure can take place
      outside the cath lab in a less resource intensive environment. Hospitals save
      resources when the higher price of the Reveal LINQ does not outweigh these
      savings.

PMID- 26293625
TI  - Ambulatory cardiac arrhythmias in relation to mild hypokalaemia and prognosis in
      community dwelling middle-aged and elderly subjects.
AB  - AIMS: Severe hypokalaemia can aggravate arrhythmia tendency and prognosis, but
      less is known about risk of mild hypokalaemia, which is a frequent finding. We
      examined the associations between mild hypokalaemia and ambulatory cardiac
      arrhythmias and their prognosis. METHODS AND RESULTS: Subjects from the cohort of
      the 'Copenhagen Holter Study' (n = 671), with no history of manifest
      cardiovascular (CV) disease or stroke, were studied. All had laboratory tests and
      48-h ambulatory electrocardiogram (ECG) recording. The median follow-up was 6.3
      years. p-Potassium was inversely associated with frequency of premature
      ventricular complexes (PVCs) especially in combination with diuretic treatment (r
      = -0.22, P = 0.015). Hypokalaemia was not associated with supraventricular
      arrhythmias. Subjects at lowest quintile of p-potassium (mean 3.42, range 2.7-3.6
      mmol/L) were defined as hypokalaemic. Cardiovascular mortality was higher in the
      hypokalaemic group (hazard ratio and 95% confidence intervals: 2.62 (1.11-6.18)
      after relevant adjustments). Hypokalaemia in combination with excessive PVC
      worsened the prognosis synergistically; event rates: 83 per 1000 patient-year in
      subjects with both abnormalities, 10 and 15 per 1000 patient-year in those with
      one abnormality, and 3 per 1000 patient-year in subjects with no abnormality. One
      variable combining hypokalaemia with excessive supraventricular arrhythmias gave
      similar results in univariate analysis, but not after multivariate adjustments.
      CONCLUSION: In middle-aged and elderly subjects with no manifest heart disease,
      mild hypokalaemia is associated with increased rate of ventricular but not
      supraventricular arrhythmias. Hypokalaemia interacts synergistically with
      increased ventricular ectopy to increase the risk of adverse events.

PMID- 26293643
TI  - Overexpression of ubiquitin carboxyl terminal hydrolase-L1 enhances multidrug
      resistance and invasion/metastasis in breast cancer by activating the MAPK/Erk
      signaling pathway.
AB  - Multidrug resistant (MDR) cancer cells overexpressing P-glycoprotein (P-gp)
      exhibit enhanced invasive/metastatic ability as compared with the sensitive
      cells. We aimed to clarify the mechanism underlying this observation and found
      that during the development of drug resistance to adriamycin in MCF7 cells, the
      elevated expression of UCH-L1 coincides with the up-regulation of MDR1, CD147,
      MMP2, and MMP9 as well as increased cellular migration/invasion. Overexpression
      of UCH-L1 in MCF7 cells up-regulated MDR1, CD147, MMP2, and MMP9, which conferred
      MDR and promoted migration/invasion. On the other hand, silencing of UCH-L1 in
      MCF7/Adr cells led to the opposite effect. Immunohistochemistry in 203 breast
      cancer samples revealed that UCH-L1 expression is positively correlated with P
      gp, CD147, MMP2, and MMP9 expression and standard tumor spread indicators. Kaplan
      Meier survival analysis indicated a correlation between UCH-L1 expression and
      shorter recurrent and survival times. Moreover, UCH-L1-overexpressing clones
      treated with U0126 (an Erk1/2-specific inhibitor) significantly decreased the
      expression of MDR1, CD147, MMP2, and MMP9. These data indicate that UCH-L1 may
      assume a dual role, because it had intrinsic stimulatory effects on tumor
      migration/invasion and increased MDR. (c) 2015 Wiley Periodicals, Inc.

PMID- 26293645
TI  - Is there a stronger graft-versus-leukemia effect using HLA-haploidentical donors
      compared with HLA-identical siblings?
AB  - Haploidentical hematopoietic stem cell transplants (HSCTs) are increasingly used,
      but it is unknown whether they have a stronger graft-versus-leukemia (GVL)
      effect. We analyzed 10 679 acute leukemia patients who underwent HSCT from an HLA
      matched sibling donor (MSD, n=9815) or a haploidentical donor (?2 HLA-antigen
      disparity, n=864) between 2007 and 2012, reported to the European Group for Blood
      and Marrow Transplantation. In a Cox regression model, acute and chronic graft
      versus-host disease (GVHD) was added as time-dependent variables. There was no
      difference in probability of relapse between recipients of haploidentical and MSD
      grafts. Factors of importance for relapse after T-cell-replete grafts included
      remission status at HSCT, Karnofsky score ?80, acute GVHD of grade II or higher
      and chronic GVHD (P<10(-5)). Patients with post-transplant cyclophosphamide
      (n=194) had similar outcome as other T-cell-replete haploidentical transplants
      (n=369). Non-relapse mortality was significantly higher in the haploidentical
      group compared with that in MSD patients (P<10(-5)). Leukemia-free survival was
      superior in the MSD patients receiving T-cell-replete (P<10(-5)) or T-cell
      depleted grafts (P=0.0006). The risk of relapse was the same in acute leukemia
      patients who received haploidentical donor grafts as in those given MSD
      transplants, suggesting a similar GVL effect. 

PMID- 26293644
TI  - Comparative Effectiveness of Web-Based vs. Educator-Delivered HIV Prevention for
      Adolescent Substance Users: A Randomized, Controlled Trial.
AB  - BACKGROUND: Young people who engage in substance use are at risk for becoming
      infected with HIV and diseases with similar transmission dynamics. Effective
      disease prevention programs delivered by prevention specialists exist but are
      rarely provided in systems of care due to staffing/resource constraints and
      operational barriers-and are thus of limited reach. Web-based prevention
      interventions could possibly offer an effective alternative to prevention
      specialist-delivered interventions and may enable widespread, cost-effective
      access to evidence-based prevention programming. Previous research has shown the
      HIV/disease prevention program within the Web-based therapeutic education system
      (TES) to be an effective adjunct to a prevention specialist-delivered
      intervention. The present study was the first randomized, clinical trial to
      evaluate the comparative effectiveness of this Web-based intervention as a
      standalone intervention relative to a traditional, prevention specialist
      delivered intervention. METHODS: Adolescents entering outpatient treatment for
      substance use participated in this multi-site trial. Participants were randomly
      assigned to either a traditional intervention delivered by a prevention
      specialist (n=72) or the Web-delivered TES intervention (n=69). Intervention
      effectiveness was assessed by evaluating changes in participants' knowledge about
      HIV, hepatitis, and sexually transmitted infections, intentions to engage in
      safer sex, sex-related risk behavior, self-efficacy to use condoms, and condom
      use skills. FINDINGS: Participants in the TES intervention achieved significant
      and comparable increases in HIV/disease-related knowledge, condom use self
      efficacy, and condom use skills and comparable decreases in HIV risk behavior
      relative to participants who received the intervention delivered by a prevention
      specialist. Participants rated TES as easier to understand. CONCLUSION: This
      study indicates that TES is as effective as HIV/disease prevention delivered by a
      prevention specialist. Because technology-based interventions such as TES have
      high fidelity, are inexpensive and scalable, and can be implemented in a wide
      variety of settings, they have the potential to greatly increase access to
      effective prevention programming.

PMID- 26293649
TI  - Service user and clinical perspectives of psychiatric advance directives in New
      Zealand.
AB  - Advance care planning is becoming an increasingly important feature of health
      service provision. Although the New Zealand Mental Health Commission has
      advocated strongly for the provision of advance directives in mental health
      services, little is known about clinician or service user views on advance
      directives. The aim of the study was to survey the perspectives of service users
      and clinicians on the use of psychiatric advance directives. The study used an
      anonymous online survey to collect data from 110 mental health service users and
      175 clinicians. Survey items included existing knowledge, preferred content and
      potential benefits of advance directives. Descriptive statistics and intergroup
      comparisons were conducted. Over 90% of service users and clinicians agreed that
      they support advance directives in mental health. There were similarities in the
      preferred content of an advance directive across the two groups, particularly
      regarding the notification of support persons, cultural support and preferred
      methods of de-escalation. Significant differences in opinion were found regarding
      the use of coercive measures and the ability of mental health legislation to
      override advance directives. The results indicate strong support for the use of
      advance directives within New Zealand mental health services, as well as for
      further research in the area. 

PMID- 26293648
TI  - The influence of simulated cataract on retinal vessel oximetry measurements.
AB  - PURPOSE: To assess the impact of human crystalline lens opacification and
      yellowing, similar to that observed in patients with cataracts, on retinal vessel
      blood oxygen saturation measurements using custom manufactured soft contact
      lenses. METHODS: Ten healthy, non-smoking individuals were enrolled for this
      study. All subjects underwent digital blood pressure measurements, assessment of
      non-contact intra-ocular pressure, pupil dilation and retinal vessel oximetry
      using dual-wavelength photography (Oximetry Module, Imedos Systems). To simulate
      lens changes, three different contact lenses were inserted, one to simulate
      opacities followed by two more lenses to simulate different levels of lens
      yellowing (Cantor & Nissel). RESULTS: The measurements obtained showed an
      opposite change in arterial and venous oxygen saturation and optical density
      ratio across conditions, resulting in a statistically significant difference in
      arterial minus venous oxygen saturation value (p = 0.003). However, this
      difference was only significant for the 'opacity' condition but not for the
      'yellowing' conditions. CONCLUSION: Lenticular changes such as cataracts can
      impact on spectrophotometric analysis in particular dual-wavelength retinal
      vessel oximetry. Hence, lenticular assessment and cataract grading should be
      considered when assessing elderly individuals and patient groups developing
      cataract earlier in life such as those suffering from diabetes mellitus.

PMID- 26293646
TI  - Targeting IL-17A in multiple myeloma: a potential novel therapeutic approach in
      myeloma.
AB  - We have previously demonstrated that interleukin-17A (IL-17) producing T helper
      17 cells are significantly elevated in blood and bone marrow (BM) in multiple
      myeloma (MM) and IL-17A promotes MM cell growth via the expression of IL-17
      receptor. In this study, we evaluated anti-human IL-17A human monoclonal antibody
      (mAb), AIN457 in MM. We observe significant inhibition of MM cell growth by
      AIN457 both in the presence and the absence of BM stromal cells (BMSCs). Although
      IL-17A induces IL-6 production, AIN457 significantly downregulated IL-6
      production and MM cell adhesion in MM-BMSC co-culture. AIN457 also significantly
      inhibited osteoclast cell differentiation. More importantly, in the SCIDhu model
      of human myeloma administration of AIN457 weekly for 4 weeks after the first
      detection of tumor in mice led to a significant inhibition of tumor growth and
      reduced bone damage compared with isotype control mice. To understand the
      mechanism of action of anti-IL-17A mAb, we report, here, that MM cells express IL
      17A. We also observed that IL-17A knockdown inhibited MM cell growth and their
      ability to induce IL-6 production in co-cultures with BMSC. These pre-clinical
      observations suggest efficacy of AIN457 in myeloma and provide the rationale for
      its clinical evaluation for anti-myeloma effects and for improvement of bone
      disease. 

PMID- 26293647
TI  - Indication and management of allogeneic stem cell transplantation in primary
      myelofibrosis: a consensus process by an EBMT/ELN international working group.
AB  - The aim of this work is to produce recommendations on the management of
      allogeneic stem cell transplantation (allo-SCT) in primary myelofibrosis (PMF). A
      comprehensive systematic review of articles released from 1999 to 2015 (January)
      was used as a source of scientific evidence. Recommendations were produced using
      a Delphi process involving a panel of 23 experts appointed by the European
      LeukemiaNet and European Blood and Marrow Transplantation Group. Key questions
      included patient selection, donor selection, pre-transplant management,
      conditioning regimen, post-transplant management, prevention and management of
      relapse after transplant. Patients with intermediate-2- or high-risk disease and
      age <70 years should be considered as candidates for allo-SCT. Patients with
      intermediate-1-risk disease and age <65 years should be considered as candidates
      if they present with either refractory, transfusion-dependent anemia, or a
      percentage of blasts in peripheral blood (PB) >2%, or adverse cytogenetics. Pre
      transplant splenectomy should be decided on a case by case basis. Patients with
      intermediate-2- or high-risk disease lacking an human leukocyte antigen (HLA)
      matched sibling or unrelated donor, should be enrolled in a protocol using HLA
      non-identical donors. PB was considered the most appropriate source of
      hematopoietic stem cells for HLA-matched sibling and unrelated donor transplants.
      The optimal intensity of the conditioning regimen still needs to be defined.
      Strategies such as discontinuation of immune-suppressive drugs, donor lymphocyte
      infusion or both were deemed appropriate to avoid clinical relapse. In
      conclusion, we provided consensus-based recommendations aimed to optimize allo
      SCT in PMF. Unmet clinical needs were highlighted. 

PMID- 26293650
TI  - TBK1 inhibitors: a review of patent literature (2011 - 2014).
AB  - INTRODUCTION: TANK-binding kinase 1 (TBK1) is a noncanonical IkappaB kinase
      family member that regulates the innate immune response. Misregulation of TBK1
      activity can promote inflammatory disorders and oncogenesis; therefore, TBK1
      inhibitors are considered a promising therapy for inflammation and cancer. AREAS
      COVERED: In this review, the authors provide information on the role of TBK1 in
      human health and on recently developed inhibitors from patents granted from 2011
      to 2014. The reader will gain an understanding of the mechanisms of TBK1 function
      as well as the structure and biological activity of recently developed TBK1
      inhibitors. Google and NCBI search engines were used to find relevant patents and
      clinical information using "TBK1 inhibitor" as the search term. EXPERT OPINION:
      The role of TBK1 in various diseases has prompted the further investigation of
      significant targets. Although research on TBK1 inhibitors has increased over the
      last few years, only a few inhibitors of this kinase have been identified. In
      addition, almost all of the chemical inhibitors are modified from different
      scaffolds and/or chemotypes of pyrimidine. Specifically, compound BX795 is the
      representative one, which was first patented as a potent TBK1 inhibitor. Even
      though some compounds have displayed interesting potential inhibition and
      selectivity of TBK1 in vitro and in in vivo trials, the development of more
      efficient and selective TBK1 inhibitors is still required.

PMID- 26293651
TI  - Effect of intra-uterine growth restriction on long-term fertility in boars.
AB  - The present study assessed the effect of birthweight on reproductive performance,
      including a possible mechanism, in male pigs. Ten newborn male piglets, including
      five normal birthweight (NBW) piglets and five intra-uterine growth restricted
      (IUGR) piglets, were used in the study. All piglets were weaned on Day 28 and fed
      the same diet during the experiment (10 months). Average daily weight gain, feed
      intake and the feed conversion ratio were higher in NBW than IUGR piglets.
      Similarly, testis volume and the number of Leydig and Sertoli cells in the distal
      portion of the testes were higher in NBW than IUGR piglets (P<0.05). Semen volume
      (P<0.05) and the total number of spermatozoa per ejaculate (P=0.08) were lower in
      IUGR boars. Testosterone concentrations on Day 141 and prostaglandin E2
      concentrations on Days 82 and 141 were higher in IUGR than NBW boars (P<0.05).
      The malondialdehyde content of seminal plasma was higher in IUGR boars, whereas
      sperm glutathione peroxidase activity was lower in IUGR versus NBW boars
      (P<0.05). Expression of DNA methyltransferase (Dnmt) genes Dnmt1, Dnmt3a, histone
      lysine N-methyltransferase (Suv39h2), and lysine (K)-specific demethylase Kdm4a
      was upregulated in testes from IUGR boars. These findings suggest that growth
      restriction affects sperm production via reproductive organ development and
      epigenetic regulation.

PMID- 26293652
TI  - Outcomes and Complications of Lead Removal: Can We Establish a Risk
      Stratification Schema for a Collaborative and Effective Approach?
AB  - BACKGROUND: Removal of an entire cardiovascular implantable electronic device is
      associated with morbidity and mortality. We sought to establish a risk
      classification scheme according to the outcomes of transvenous lead removal in a
      single center, with the goal of using that scheme to guide electrophysiology lab
      versus operating room extraction. METHODS: Consecutive patients undergoing
      transvenous lead removal from January 2001 to October 2012 at Mayo Clinic were
      retrospectively reviewed. RESULTS: A total of 1,378 leads were removed from 652
      (age 64 +/- 17 years, M 68%) patients undergoing 702 procedures. Mean (standard
      deviation) lead age was 57.6 (58.8) months. Forty-four percent of leads required
      laser-assisted extraction. Lead duration (P < 0.001) and an implantable
      cardioverter defibrillator (ICD) lead (P < 0.001) were associated with the need
      for laser extraction and procedure failure (P < 0.0001 and P = 0.02). The major
      complication rate was 1.9% and was significantly associated with longer lead
      duration (odds ratio: 1.2, 95% confidence interval: 1.1-1.3; P < 0.001). High
      risk patients (with a >10-year-old pacing or a >5-year-old ICD lead) had
      significantly higher major events than moderate-risk (with pacing lead 1-10 years
      old or ICD lead 1-5 years old) and low-risk (any lead <=1-year-old) patients
      (5.3%, 1.2%, and 0%, respectively; P < 0.001). CONCLUSIONS: Transvenous lead
      removal is highly successful, with few serious procedural complications. We
      propose a risk stratification scheme that may categorize patients as low,
      moderate, and high risk for lead extraction. Such a strategy may guide which
      extractions are best performed in the operating room.

PMID- 26293653
TI  - Medicaid IBCLC Service Coverage following the Affordable Care Act and the Center
      for Medicare and Medicaid Services Update.
AB  - BACKGROUND: International Board Certified Lactation Consultants (IBCLCs) are
      associated with increased rates and duration of breastfeeding. Recent US
      legislation offers opportunities for private and public insurers to include IBCLC
      services as a covered benefit. OBJECTIVE: To explore US states' Medicaid coverage
      of IBCLC services following January 2014 legislative expansions of coverage for
      preventive health services. METHODS: To assess IBCLC reimbursement practices, 20
      states, stratified by Medicaid expansion (yes/no) and 3-month exclusive
      breastfeeding rates, were selected to participate. An electronic survey was sent
      to Medicaid and Maternal Health Directors, breastfeeding coordinators, and
      Special Supplemental Nutrition Program for Women, Infants, and Children (WIC)
      coordinators between July and December 2014. Email follow-ups clarified missing
      or ambiguous responses. RESULTS: Of the 15 states responding, 9 had Medicaid
      expansion. None of the states permitted IBCLCs to bill for services autonomously.
      In 9 states, IBCLC services were covered with some type of stipulation, for
      example, billing under a physician. Of the 9 states with IBCLC coverage, 7 had
      accepted Medicaid expansion. States with higher rates of exclusive breastfeeding
      were also more likely to provide IBCLC coverage. CONCLUSION: Recent legislative
      changes to public and private insurance that could expand coverage of IBCLCs have
      not yielded appreciable changes, particularly in states without Medicaid
      expansion. There is a need for research on the effects of adopting expanded
      coverage for IBCLCs and advocacy to do so.

PMID- 26293654
TI  - Community-Based Participatory Initiatives to Increase Breastfeeding Rates in
      Indiana.
AB  - In 2012, the Centers for Disease Control and Prevention awarded the Indiana State
      Department of Health funding for breastfeeding activities. The grant, issued in
      part in response to the 2011 Surgeon General's Call to Action to Support
      Breastfeeding, focused on providing funding and technical support to small
      community-based organizations to address challenges encountered by breastfeeding
      mothers. Indiana used the funds to develop the Community Breastfeeding Support
      Initiative (CBSI). The goal was to provide funding and technical support to small
      community-based organizations to carry out self-selected projects in their
      communities. The 13 CBSI programs served 1345 individual clients (n = 3664
      visits) during the 9-month period. This article provides valuable information
      about collaboration at the state level and the supporting infrastructure in place
      to carry out this project. Our findings about the number of clients served,
      number of visits, community-specific programs and activities, and lessons learned
      can be used by other organizations as they plan breastfeeding support programs
      for their community. 

PMID- 26293655
TI  - Assessment of an automated capillary system for Plasmodium vivax microsatellite
      genotyping.
AB  - BACKGROUND: Several platforms have been used to generate the primary data for
      microsatellite analysis of malaria parasite genotypes. Each has relative
      advantages but share a limitation of being time- and cost-intensive. A
      commercially available automated capillary gel cartridge system was assessed in
      the microsatellite analysis of Plasmodium vivax diversity in the Peruvian Amazon.
      METHODS: The reproducibility and accuracy of a commercially-available automated
      capillary system, QIAxcel, was assessed using a sequenced PCR product of 227 base
      pairs. This product was measured 42 times, then 27 P. vivax samples from Peruvian
      Amazon subjects were analyzed with this instrument using five informative
      microsatellites. Results from the QIAxcel system were compared with a Sanger-type
      sequencing machine, the ABI PRISM((r)) 3100 Genetic Analyzer. RESULTS:
      Significant differences were seen between the sequenced amplicons and the results
      from the QIAxcel instrument. Different runs, plates and cartridges yielded
      significantly different results. Additionally, allele size decreased with each
      run by 0.045, or 1 bp, every three plates. QIAxcel and ABI PRISM systems differed
      in giving different values than those obtained by ABI PRISM, and too many (i.e.
      inaccurate) alleles per locus were also seen with the automated instrument.
      CONCLUSIONS: While P. vivax diversity could generally be estimated using an
      automated capillary gel cartridge system, the data demonstrate that this system
      is not sufficiently precise for reliably identifying parasite strains via
      microsatellite analysis. This conclusion reached after systematic analysis was
      due both to inadequate precision and poor reproducibility in measuring PCR
      product size.

PMID- 26293656
TI  - Impact of abdominal drainage systems on postoperative complication rates
      following liver transplantation.
AB  - BACKGROUND: Depending on the extent of surgery, coagulation status and the number
      of anastomoses, drains are routinely used during liver transplantation. The aim
      of this study was to compare different drain types with regard to abdominal
      complication rates. METHODS: All consecutive full-size orthotopic liver
      transplantations (LTX) performed over a 7-year period were included in this
      retrospective analysis. Abdominal drain groups were divided into open-circuit
      drains and closed-circuit drains. Data are reported as total number (%) or median
      (range); for all comparisons a p value <0.05 was considered statistically
      significant. RESULTS: A total of 256 LTX [age 56.89 (0.30-75.21) years; MELD 14.5
      (7-40)] was included; 56 (21.8 %) patients received an open-circuit Easy Flow
      Drain (Group 1) and 200 (78.2 %) a closed-circuit Robinson Drainage System (Group
      2). For Groups 1 and 2, overall infection rates were 78.6 and 56 % (p = 0.001),
      abdominal infection rates 50.82 and 21.92 % (p = 0.001), yeast infection rates 37
      and 23 % (p = 0.02), abdominal bleeding rates 26.78 and 17 % (p = 0.07), biliary
      complication rates 14.28 and 13.5 % (p = 0.51), respectively. CONCLUSIONS: In
      this retrospective series, open-circuit drains were associated with more
      abdominal complications, mainly due to intraabdominal infections, than were
      closed-circuit drains.

PMID- 26293657
TI  - Cognitive behavioral group intervention for pain and well-being in children with
      juvenile idiopathic arthritis: a study of feasibility and preliminary efficacy.
AB  - BACKGROUND: Pain is still a part of everyday living for several children with
      juvenile idiopathic arthritis (JIA) despite improvement in treatment.
      Psychological interventions may contribute to diminish pain complaints and
      improve well-being in children with JIA. Only few studies have investigated the
      efficacy of psychological therapy in children with arthritis and with mixed
      results. The aim of the study was to evaluate the feasibility and preliminary
      efficacy of a cognitive behavioral therapy group intervention for children with
      JIA and their parents. METHODS: Nineteen children with JIA and their parents were
      allocated to six sessions' group cognitive-behavioral therapy (n = 9) or a
      waitlist control condition (n = 10). Results were measured from self-reported
      scales and one-week pain diaries. Clinical data was collected by a
      rheumatologist. RESULTS: The participation rate was low; 33 % of the invited
      families participated. However, the participants rated the intervention's
      credibility and satisfaction with the intervention as high. The dropout rate was
      low and attendance rate high. Increased quality of life and improvements in
      adaptive pain cognitions was reported in the intervention condition compared to
      the waitlist condition, whereas no differences were found for pain and functional
      disability. The disease activity increased in the treatment condition but not in
      the control condition. CONCLUSIONS: The feasibility of this study seemed high
      with regards to the acceptability of the families participating in the
      intervention. However, the feasibility in general was challenged by
      implementation problems with a low participation rate. A reduction in pain after
      the intervention was not found even though pain management was the main target in
      the intervention. Preliminary analysis showed that although the severity of the
      disease status increased, an increase in quality of life, reduction in pain
      catastrophizing, and an improvement in adaptive pain cognitions (the beliefs in
      controlling pain and self-efficacy) were seen in the intervention condition. The
      study highlights the importance of considering the disease status when evaluating
      the efficacy of a psychological intervention in children with arthritis.
      Conclusions on the strength of the efficacy require further research in a large,
      randomized controlled trial.

PMID- 26293658
TI  - Breast cancer tumour growth modelling for studying the association of body size
      with tumour growth rate and symptomatic detection using case-control data.
AB  - INTRODUCTION: A large body size is associated with larger breast cancer tumours
      at diagnosis. Standard regression models for tumour size at diagnosis are not
      sufficient for unravelling the mechanisms behind the association. METHODS: Using
      Swedish case-control data, we identified 1352 postmenopausal women with incident
      invasive breast cancer diagnosed between 1993 and 1995. We used a novel
      continuous tumour growth model, which models tumour sizes at diagnosis through
      three submodels: for tumour growth, time to symptomatic detection, and screening
      sensitivity. Tumour size at other time points is thought of as a latent variable.
      RESULTS: We quantified the relationship between body size with tumour growth and
      time to symptomatic detection. High body mass index and large breast size are,
      respectively, significantly associated with fast tumour growth rate and delayed
      time to symptomatic detection (combined P value = 5.0 * 10(-5) and individual P
      values = 0.089 and 0.022). We also quantified the role of mammographic density in
      screening sensitivity. CONCLUSIONS: The times at which tumours will be
      symptomatically detected may vary substantially between women with different
      breast sizes. The proposed tumour growth model represents a novel and useful
      approach for quantifying the effects of breast cancer risk factors on tumour
      growth and detection.

PMID- 26293659
TI  - Human trafficking and health: a cross-sectional survey of NHS professionals'
      contact with victims of human trafficking.
AB  - OBJECTIVES: (1) To estimate the proportion of National Health Service (NHS)
      professionals who have come into contact with trafficked people and (2) to
      measure NHS professionals' knowledge and confidence to respond to human
      trafficking. DESIGN: A cross-sectional survey. SETTING: Face-to-face mandatory
      child protection and/or vulnerable adults training sessions at 10 secondary
      healthcare provider organisations in England, and meetings of the UK College of
      Emergency Medicine. PARTICIPANTS: 782/892 (84.4%) NHS professionals participated,
      including from emergency medicine, maternity, mental health, paediatrics and
      other clinical disciplines. MEASURES: Self-completed questionnaire developed by
      an expert panel. Questionnaire asks about prior training and contact with
      potential victims of trafficking, perceived and actual human trafficking
      knowledge, confidence in responding to human trafficking, and interest in future
      human trafficking training. RESULTS: 13% participants reported previous contact
      with a patient they knew or suspected of having been trafficked; among maternity
      services professionals this was 20.4%. However, 86.8% (n=679) reported lacking
      knowledge of what questions to ask to identify potential victims and 78.3%
      (n=613) reported that they had insufficient training to assist trafficked people.
      71% (n=556), 67.5% (n=528) and 53.4% (n=418) lacked confidence in making
      appropriate referrals for men, women and children, respectively, who had been
      trafficked. 95.3% (n=746) of respondents were unaware of the scale of human
      trafficking in the UK, and 76.5% (n=598) were unaware that calling the police
      could put patients in more danger. Psychometric analysis showed that subscales
      measuring perceived knowledge, actual knowledge and confidence to respond to
      human trafficking demonstrated good internal consistency (Cronbach's alphas 0.93,
      0.63 and 0.64, respectively) and internal correlations. CONCLUSIONS: NHS
      professionals working in secondary care are in contact with potential victims of
      human trafficking, but lack knowledge and confidence in how to respond
      appropriately. Training is needed, particularly for maternity staff, on how to
      identify and respond to victims' needs, including through making safe referrals.

PMID- 26293660
TI  - Segmentation of the lateral femoral notch sign with MRI using a new measurement
      technique.
AB  - BACKGROUND: The goal of this present study was to precisely determine the
      dimension and location of the impaction fracture on the lateral femoral condyle
      in patients with an ACL rupture. METHODS: All patients with post-injury bi-plane
      radiographs and MRI images after sustaining a tear to the anterior cruciate
      ligament were included. Lateral radiographs of the affected knee were inspected
      for a lateral femoral notch sign. MRIs of patients with a lateral condylopatellar
      sulcus >=1.5 mm were used to segment and measure the lateral condylopatellar
      sulcus. The MRI examination was interpreted by an expert in musculoskeletal
      radiology. The study was approved by the ethics committee of the state of
      Salzburg. RESULTS: A "lateral femoral notch sign"was seen in 50 patients. The
      average total surface area of the lateral femoral condyle was 3271.7 mm(2) (SD
      739.5 mm(2)). The defect had a mean surface area of 266.1 mm(2) (SD 125.5 mm(2)),
      a mean volume of 456.5 mm(3) (SD 278.5 mm(3)), a mean depth of 3.0 mm (SD 0.8
      mm). On average 169 mm(2) (SD 99.6 mm(2)) of the surface of the condyle were
      affected by the impaction fracture which corresponds to 5.2% (SD 2.8%) of the
      surface of the lateral femoral condyle. In 51 % the impaction fracture was
      located in the central-external area of the femoral condyle. CONCLUSIONS: In
      cases of a clinically suspected ACL rupture lateral radiographs of the knee
      should be checked for a lateral femoral notch sign further MRI for confirmation
      should be performed. Knowing of the precise defect on the lateral femoral condyle
      is an additionally valuable information, as concomitant injuries to a rupture of
      the anterior cruciate ligament increase the risk for early-onset osteoarthritis
      in the future.

PMID- 26293661
TI  - Histoprotective effect of vitamin D against carbon tetrachloride nephrotoxicity
      in rats.
AB  - This study investigated the protective effect of vitamin D against carbon
      tetrachloride (CCl4)-induced nephrotoxicity in rats. Adult male Wistar albino
      rats were divided into four groups ((A) control; (B) 10-week exposure to CCl4;
      (C) 10-week exposure to CCl4 + vitamin D treatment; and (D) 10-week exposure to
      CCl4 + 12 weeks of vitamin D treatment). The CCl4 dose (1.5 ml kg(-1)) was
      injected subcutaneously twice a week, while the 0.5 mg kg(-1) dose of vitamin D
      was administered intraperitoneally every day, as appropriate for each group.
      Whole animal and kidney weights as well as serum urea, creatinine, and glucose
      levels were measured. Kidney tissue sections were stained with hematoxylin-eosin,
      Masson's trichrome, and periodic acid-Schiff. Tubular and glomerular degeneration
      were detected in the kidney tissues of CCl4-treated rats, together with
      dilatation and vacuolization within the tubules and hemorrhage in the
      intertubular region. In the kidney glomeruli; congestion, atrophy, and adhesion
      to parietal layer were observed. Tissue disorganization and aggregation of
      Bowman's capsules were noted. Mononuclear cell infiltration was observed between
      the glomeruli and the tubules. In contrast, the kidney sections and functional
      parameters of vitamin D-treated rats were similar to the controls, suggesting
      that vitamin D treatment is able to reduce renal damage. 

PMID- 26293663
TI  - The validity of clinical practice guidelines for empirical use of oseltamivir for
      influenza in Thai children.
AB  - BACKGROUND: Clinical practice guidelines for influenza have been implemented to
      maximise the appropriate use of empirical oseltamivir; however, good predictive
      values are required. METHODS: Between October 2011 and September 2013, children
      aged < 15 years who presented at the Bamrasnaradura Infectious Diseases Institute
      with an influenza-like illness plus either (i) pneumonia or (ii) being in a
      higher risk group for influenza complications were prospectively enrolled.
      Respiratory specimens were taken for real-time polymerase chain reaction testing
      (RT-PCR). Clinical characteristics, laboratory data and oseltamivir therapy were
      recorded. RESULTS: 85 cases were enrolled. Of these, the proportions of those
      with pneumonia, who were aged < 2 years and who had underlying diseases were
      74.1%, 56.5% and 38.8%, respectively. RT-PCR detected respiratory syncytial
      virusamong (35.3%), influenza (22.3by%), adenovirus (14.1%), human
      metapneumovirus (5.9%), para-influenza (3.5%) and no viruses (25.9 %). Pneumonia
      (OR 0.16, 95% CI 0.05-0.50) and having two clinical criteria (OR 0.24, 95% CI
      0.08-0.76) were significantly negative predictors of influenza. Having cluster
      transmissions (OR 5.18, 95% CI 1.38-19.37) and a monocyte proportion >7% (OR
      3.58, 95% CI 1.15-11.17) were significantly positive predictors of influenza. The
      mean (SD) percentage of influenza-like illness during the study period was 7.04
      (2.02). CONCLUSIONS: Clinical criteria guidelines yielded a low predictive value
      (22.3%) for influenza in children. Seasonality, cluster transmission, white blood
      cell and differential counts may be helpful in diagnosing influenza. Nonetheless,
      empirical oseltamivir should not be delayed for those in need.

PMID- 26293662
TI  - Mutations in PIGY: expanding the phenotype of inherited
      glycosylphosphatidylinositol deficiencies.
AB  - Glycosylphosphatidylinositol (GPI)-anchored proteins are ubiquitously expressed
      in the human body and are important for various functions at the cell surface.
      Mutations in many GPI biosynthesis genes have been described to date in patients
      with multi-system disease and together these constitute a subtype of congenital
      disorders of glycosylation. We used whole exome sequencing in two families to
      investigate the genetic basis of disease and used RNA and cellular studies to
      investigate the functional consequences of sequence variants in the PIGY gene.
      Two families with different phenotypes had homozygous recessive sequence variants
      in the GPI biosynthesis gene PIGY. Two sisters with c.137T>C (p.Leu46Pro) PIGY
      variants had multi-system disease including dysmorphism, seizures, severe
      developmental delay, cataracts and early death. There were significantly reduced
      levels of GPI-anchored proteins (CD55 and CD59) on the surface of patient-derived
      skin fibroblasts (~20-50% compared with controls). In a second, consanguineous
      family, two siblings had moderate development delay and microcephaly. A
      homozygous PIGY promoter variant (c.-540G>A) was detected within a 7.7 Mb region
      of autozygosity. This variant was predicted to disrupt a SP1 consensus binding
      site and was shown to be associated with reduced gene expression. Mutations in
      PIGY can occur in coding and non-coding regions of the gene and cause variable
      phenotypes. This article contributes to understanding of the range of disease
      phenotypes and disease genes associated with deficiencies of the GPI-anchor
      biosynthesis pathway and also serves to highlight the potential importance of
      analysing variants detected in 5'-UTR regions despite their typically low
      coverage in exome data. 

PMID- 26293664
TI  - Assessing the association between homocysteine and cognition: reflections on
      Bradford Hill, meta-analyses, and causality.
AB  - Hyperhomocysteinemia is a recognized risk factor for cognitive decline and
      incident dementia in older adults. Two recent reports addressed the cumulative
      epidemiological evidence for this association but expressed conflicting opinions.
      Here, the evidence is reviewed in relation to Sir Austin Bradford Hill's criteria
      for assessing "causality," and the latest meta-analysis of the effects of
      homocysteine-lowering on cognitive function is critically examined. The meta
      analysis included 11 trials, collectively assessing 22,000 individuals, that
      examined the effects of B vitamin supplements (folic acid, vitamin B12, vitamin
      B6) on global or domain-specific cognitive decline. It concluded that
      homocysteine-lowering with B vitamin supplements has no significant effect on
      cognitive function. However, careful examination of the trials in the meta
      analysis indicates that no conclusion can be made regarding the effects of
      homocysteine-lowering on cognitive decline, since the trials typically did not
      include individuals who were experiencing such decline. Further definitive trials
      in older adults experiencing cognitive decline are still urgently needed.

PMID- 26293666
TI  - Evaluation of the peripapillary retinal nerve fiber layer and ganglion cell-inner
      plexiform layer measurements in patients with iron deficiency anemia with optical
      coherence tomography.
AB  - OBJECTIVE: To evaluate the thickness of the peripapillary retinal fiber layer
      (RNFL) and macula ganglion cell-inner plexiform layer (GCL+) using optical
      coherence tomography (OCT) in patients with iron deficiency (ID) anemia. METHODS:
      This study included 73 eyes of 39 patients with ID anemia and 68 eyes of 34 age-
      and sex-matched healthy subjects. The measurements included the peripapillary
      RNFL thicknesses as average, 4 quadrant and 12 clock-hour (CH) based and macula
      GCL+ thicknesses as average and 6 quadrant based. All measurements were completed
      with Cirrus HD-OCT and the results were compared between the groups. RESULTS: A
      total of 73 eyes of 39 patients with ID anemia and 68 eyes of 34 healthy subjects
      were included to the study. Regarding peripapillary RNFL thicknesses of the study
      and control patients, the values of average and quadrants revealed no significant
      differences between the groups. In CH sectors comparison, peripapillary RNFL
      thicknesses were significantly decreased only in CH4 (68.7 +/- 14.5 MUm in study
      versus 72.0 +/- 13.4 MUm in control patients, p = 0.049) and CH5 (93.4 +/-
      20.0MUm in study versus 102.2 +/- 20.1 MUm in control patients, p = 0.01)
      sectors. All measured quadrants were statistically similar, when macula GCL+
      thicknesses were compared between the groups. When the correlations between
      peripapillary RNFL and macula GCL+ thicknesses and serum hemoglobin and ferritin
      levels of study and control patients were calculated, the only statistically
      significant parameter was the correlation of peripapillary RNFL thickness in CH10
      sector with serum ferritin level (p = 0.032, Spearman correlation coefficient:
      0.369). CONCLUSION: The study revealed that peripapillary RNFL is thinner in
      nasal-inferior quadrant in patients with ID anemia. The measurements of macula
      GCL+ thicknesses were similar between the groups. Analyzing the retinal layers
      using OCT may provide valuable information in neurodegenerative events.

PMID- 26293669
TI  - Oncocytic Variant of Medullary Thyroid Carcinoma.

PMID- 26293667
TI  - Detection of carbapenemase activity using VITEK MS: interplay of carbapenemase
      type and period of incubation.

PMID- 26293670
TI  - Should epileptiform discharges be treated?
AB  - To evaluate the impact of epileptiform discharges (EDs) that do not occur within
      seizure patterns--such as spikes, sharp waves or spike waves--on cognitive
      function and to discuss the circumstances under which treatment of EDs might be
      considered. Methods used in this article is "Review of the literature". EDs may
      disrupt short-term cognition in humans. Frequent EDs for a prolonged period can
      potentially impair long-term cognitive function in humans. However, there is
      conflicting evidence on the impact of EDs on long-term cognitive outcome because
      this relationship may be confounded by multiple factors such as underlying
      etiology, seizures, and medication effects. Limitations of existing studies
      include the lack of standardized ED quantification methods and of widely accepted
      automated spike quantification methods. Although there is no solid evidence for
      or against treatment of EDs, a non-evidence-based practical approach is
      suggested. EDs in otherwise asymptomatic individuals should not be treated
      because the risks of treatment probably outweigh its dubious benefits. A
      treatment trial for EDs may be considered when there is cognitive dysfunction or
      regression or neurologic symptoms that are unexplained by the underlying
      etiology, comorbid conditions, or seizure severity. In patients with cognitive or
      neurologic dysfunction with epilepsy or EDs, treatment may be warranted to
      control the underlying epileptic syndrome. EDs may cause cognitive or neurologic
      dysfunction in humans in the short term. There is conflicting evidence on the
      impact of EDs on long-term cognitive outcome. There is no evidence for or against
      treatment of asymptomatic ED.

PMID- 26293668
TI  - TRIM28 as a novel transcriptional elongation factor.
AB  - TRIM28 is a multidomain protein with versatile functions in transcription and DNA
      repair. Recently it was shown that this factor plays unanticipated roles in
      transcriptional elongation. TRIM28 was shown to stabilize the pausing of RNA
      polymerase II (Pol II) close to the transcriptional start site in many
      unactivated genes, permitting Pol II accumulation and readying genes for
      induction. In addition, the factor was shown to respond rapidly to signals
      accompanying transcriptional activation permitting the productive elongation of
      RNA by previously paused Pol II. We discuss here critical regulatory mechanisms
      of TRIM28 in transcriptional control and DNA repair that may illuminate the novel
      roles of this factor in pausing and elongation of Pol II. 

PMID- 26293678
TI  - Efficacy of a Multicomponent Positive Psychology Self-Help Intervention: Study
      Protocol of a Randomized Controlled Trial.
AB  - BACKGROUND: Positive psychology interventions have been found to enhance well
      being and decrease clinical symptomatology. However, it is still unknown how
      flourishing can also be increased. Although multicomponent interventions seem to
      be necessary for this purpose, different formats can be used. A cost-effective
      approach could be a positive psychology-based self-help book with tailored email
      support to reach large target groups and to prevent dropout. OBJECTIVE: This
      study will evaluate the efficacy of a comprehensive multicomponent self-help
      intervention with or without email support on well-being and flourishing, and
      will seek to determine the working mechanisms underlying the intervention.
      METHODS: In this 3-armed, parallel, randomized controlled trial, 396 participants
      with low or moderate levels of well-being and without clinical symptomatology
      will be randomly assigned to (1) a self-help book condition with weekly email
      support, (2) a self-help book condition without email support but with a weekly
      information email, or (3) a waiting list control condition. Online measurements
      will be assessed at baseline, at post-test (3 months after baseline), and at 6
      and 12 months after baseline. RESULTS: The primary outcomes are well-being and
      flourishing (ie, high levels of well-being). Secondary outcomes are the well
      being components included in the intervention: positive emotion, use of
      strengths, optimism, self-compassion, resilience, and positive relations. Other
      measures include depressive and anxiety symptoms, personality traits, direct
      medical and non-medical costs, life-events, and client satisfaction. CONCLUSIONS:
      This study will add knowledge to the efficacy and cost-effectiveness of a
      multicomponent positive psychology intervention. We will also explore who can
      benefit most from this intervention. If the intervention is found to be
      effective, our results will be especially relevant for public mental health
      services, governments, and primary care. TRIAL REGISTRATION: The Netherlands
      Trial Register NTR4297;
      http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4297 (Archived by
      WebCite at http://webcitation.org/6Uwb5SUUM).

PMID- 26293680
TI  - Infection dynamics in frog populations with different histories of decline caused
      by a deadly disease.
AB  - Pathogens can drive host population dynamics. Chytridiomycosis is a fungal
      disease of amphibians that is caused by the fungus Batrachochytrium dendrobatidis
      (Bd). This pathogen has caused declines and extinctions in some host species
      whereas other host species coexist with Bd without suffering declines. In the
      early 1990s, Bd extirpated populations of the endangered common mistfrog, Litoria
      rheocola, at high-elevation sites, while populations of the species persisted at
      low-elevation sites. Today, populations have reappeared at many high-elevation
      sites where they presently co-exist with the fungus. We conducted a capture-mark
      recapture (CMR) study of six populations of L. rheocola over 1 year, at high and
      low elevations. We used multistate CMR models to determine which factors (Bd
      infection status, site type, and season) influenced rates of frog survival,
      recapture, infection, and recovery from infection. We observed Bd-induced
      mortality of individual frogs, but did not find any significant effect of Bd
      infection on the survival rate of L. rheocola at the population level. Survival
      and recapture rates depended on site type and season. Infection rate was highest
      in winter when temperatures were favourable for pathogen growth, and differed
      among site types. The recovery rate was high (75.7-85.8%) across seasons, and did
      not differ among site types. The coexistence of L. rheocola with Bd suggests that
      (1) frog populations are becoming resistant to the fungus, (2) Bd may have
      evolved lower virulence, or (3) current environmental conditions may be
      inhibiting outbreaks of the fatal disease.

PMID- 26293681
TI  - Association between Helicobacter pylori infection and osteoporosis: a systematic
      review and meta-analysis.

PMID- 26293677
TI  - Differences in the clinical courses of pediatric and adult pilocytic astrocytomas
      with progression: a single-institution study.
AB  - PURPOSE: Pilocytic astrocytoma (PA) is a World Health Organization grade I
      neoplasm that generally follows a benign course. However, in some patients, PA
      exhibits an aggressive clinical course. Here, we examined the clinical course of
      pediatric and adult PAs with progression at a single institution. METHODS:
      Between 1995 and 2013, 39 patients with PA were treated. Nineteen were pediatric
      patients (mean age, 12 years; range, 1-17 years) with a male-to-female patient
      ratio of 10:9, while 20 were adults (mean age, 36.4 years; range, 19-65 years)
      with a male-to-female ratio of 9:11. We analyzed and compared tumor location,
      extent of tumor resection, adjuvant treatment, and clinical course in all
      patients. RESULTS: In the 19 pediatric patients, tumors were located in the
      cerebellar vermis, cerebellar hemisphere, optic pathways plus hypothalamus,
      hypothalamus, brainstem, and the temporal lobe in 6 (31.6%), 5 (26.3%), 3
      (15.8%), 2 (10.5%), and 2 (10.5%) patients and 1 (5.3%) patient, respectively.
      The mass was totally, subtotally, or partially resected in 11 (57.9%), 2 (10.5%),
      and 4 (21.1%) patients, respectively; biopsies were performed in 2 (10.5%)
      patients. Immediate postoperative adjuvant treatment was carried out in 6
      patients. Tumor progression was detected in 3 patients at 3.0, 4.6, and 5.2 years
      after treatment, respectively, without significant symptoms. In the 20 adult
      patients, tumors were located in the cerebellar hemisphere, cerebellar vermis,
      hypothalamus, brainstem, cerebral hemisphere, and lateral ventricle in 5 (25%), 4
      (20%), 3 (15%), 3 (15%), 3 (15%), and 2 (10%) patients, respectively. The mass
      was totally, subtotally, or partially resected in 11 (55%) and 6 (30%) patients
      and 1 (5%) patient, respectively; biopsies were performed in 2 patients.
      Immediate adjuvant treatment was carried out in 2 patients. Progression was
      detected in 3 patients at 0.3, 0.9, and 2.5 years after treatment, respectively,
      with progressive neurologic symptoms. There was one case of disease-related
      mortality during follow-up among the adult patients. CONCLUSION: Most of the PA
      cases evaluated in this study were benign. However, tumor progression in adult
      PAs followed a more aggressive clinical course than those in pediatric PAs.

PMID- 26293679
TI  - Dimensions of distress tolerance and the moderating effects on mindfulness-based
      stress reduction.
AB  - BACKGROUND AND OBJECTIVES: This study examined the relationship between distress
      tolerance and psychosocial changes among individuals participating in Mindfulness
      Based Stress Reduction (MBSR). The objective of the analysis was to discern
      whether individuals with lower distress tolerance measured before MBSR showed
      larger reductions in perceived stress following MBSR. DESIGN AND METHODS: Data
      were collected from a sample of convenience (n = 372) using a quasi-experimental
      design. Participants completed self-report measures immediately prior to course
      enrollment and following course completion. RESULTS: Perceived stress, distress
      tolerance, and mood states showed favorable changes from pre- to post-MBSR in the
      current study. Baseline distress tolerance significantly moderated reductions on
      perceived stress, supporting the primary hypothesis that individuals with lower
      baseline distress tolerance evidenced a greater decline in perceived stress
      following MBSR. For a one-unit increase on the self-reported baseline Distress
      Tolerance Scale, reported perceived stress scores decreased by 2.5 units (p <
      .0001). CONCLUSIONS: The finding that individuals with lower baseline distress
      tolerance evidenced a greater decline in perceived stress may offer hints about
      who is most likely to benefit from MBSR and other mindfulness-based treatments.
      Identifying moderators of treatment outcomes may yield important benefits in
      matching individuals to treatments that are most likely to work for them.

PMID- 26293676
TI  - Synchronous glioblastoma and medulloblastoma in a child with mismatch repair
      mutation.
AB  - Synchronous primary malignant brain tumors are rare. We present a 5-year-old boy
      with synchronous glioblastoma and medulloblastoma. Both tumor samples had
      positive p53 stain and loss of PMS2 and MLH1 stains. The child had multiple cafe
      au lait spots and a significant family history of cancer. After subtotal
      resection of both tumors, he received craniospinal radiation with concomitant
      temozolomide followed by chemotherapy, alternating cycles of
      cisplatin/lomustine/vincristine with temozolomide. Then, he started maintenance
      treatment with cis-retinoic acid (100 mg/m(2)/day for 21 days). He remained
      asymptomatic for 34 months despite a follow-up brain MRI consistent with
      glioblastoma relapse 9 months before his death. Cis-retinoic acid may have
      contributed to prolong survival in this child with a probable biallelic mismatch
      repair syndrome. 

PMID- 26293671
TI  - Tauroursodeoxycholic acid dampens oncogenic apoptosis induced by endoplasmic
      reticulum stress during hepatocarcinogen exposure.
AB  - Hepatocellular carcinoma (HCC) is characterized by the accumulation of unfolded
      proteins in the endoplasmic reticulum (ER), which activates the unfolded protein
      response (UPR). However, the role of ER stress in tumor initiation and
      progression is controversial. To determine the impact of ER stress, we applied
      tauroursodeoxycholic acid (TUDCA), a bile acid with chaperone properties. The
      effects of TUDCA were assessed using a diethylnitrosamine-induced mouse HCC model
      in preventive and therapeutic settings. Cell metabolic activity, proliferation
      and invasion were investigated in vitro. Tumor progression was assessed in the
      HepG2 xenograft model. Administration of TUDCA in the preventive setting reduced
      carcinogen-induced elevation of alanine and aspartate aminotransferase levels,
      apoptosis of hepatocytes and tumor burden. TUDCA also reduced eukaryotic
      initiation factor 2alpha (eIf2alpha) phosphorylation, C/EBP homologous protein
      expression and caspase-12 processing. Thus, TUDCA suppresses carcinogen-induced
      pro-apoptotic UPR. TUDCA alleviated hepatic inflammation by increasing NF-kappaB
      inhibitor IkappaBalpha. Furthermore, TUDCA altered the invasive phenotype and
      enhanced metabolic activity but not proliferation in HCC cells. TUDCA
      administration after tumor development did not alter orthotopic tumor or
      xenograft growth. Taken together, TUDCA attenuates hepatocarcinogenesis by
      suppressing carcinogen-induced ER stress-mediated cell death and inflammation
      without stimulating tumor progression. Therefore, this chemical chaperone could
      represent a novel chemopreventive agent. 

PMID- 26293673
TI  - The proteomic investigation reveals interaction of mdig protein with the
      machinery of DNA double-strand break repair.
AB  - To investigate how mineral dust-induced gene (mdig, also named as mina53, MINA,
      or NO52) promotes carcinogenesis through inducing active chromatin, we performed
      proteomics analyses for the interacting proteins that were co-immunoprecipitated
      by anti-mdig antibody from either the lung cancer cell line A549 cells or the
      human bronchial epithelial cell line BEAS-2B cells. On SDS-PAGE gels, three to
      five unique protein bands were consistently observed in the complexes pulled-down
      by mdig antibody, but not the control IgG. In addition to the mdig protein,
      several DNA repair or chromatin binding proteins, including XRCC5, XRCC6, RBBP4,
      CBX8, PRMT5, and TDRD, were identified in the complexes by the proteomics
      analyses using both Orbitrap Fusion and Orbitrap XL nanoESI-MS/MS in four
      independent experiments. The interaction of mdig with some of these proteins was
      further validated by co-immunoprecipitation using antibodies against mdig and its
      partner proteins, respectively. These data, thus, provide evidence suggesting
      that mdig accomplishes its functions on chromatin, DNA repair and cell growth
      through interacting with the partner proteins. 

PMID- 26293674
TI  - Glucose transporter isoform 1 expression enhances metastasis of malignant
      melanoma cells.
AB  - The glucose transporter isoform 1 (GLUT1; SLC2A1) is a key rate-limiting factor
      in the transport of glucose into cancer cells. Enhanced GLUT1 expression and
      accelerated glycolysis have been found to promote aggressive growth in a range of
      tumor entities. However, it was unknown whether GLUT1 directly impacts
      metastasis. Here, we aimed at analyzing the expression and function of GLUT1 in
      malignant melanoma. Immunohistochemical analysis of 78 primary human melanomas on
      a tissue micro array showed that GLUT1 expression significantly correlated with
      the mitotic activity and a poor survival. To determine the functional role of
      GLUT1 in melanoma, we stably suppressed GLUT1 in the murine melanoma cell line
      B16 with shRNA. GLUT1 suppressed melanoma cells revealed significantly reduced
      proliferation, apoptosis resistance, migratory activity and matrix
      metalloproteinase 2 (MMP2) expression. In a syngeneic murine model of hepatic
      metastasis, GLUT1-suppressed cells formed significantly less metastases and
      showed increased apoptosis compared to metastases formed by control cells.
      Treatment of four different human melanoma cell lines with a pharmacological
      GLUT1 inhibitor caused a dose-dependent reduction of proliferation, apoptosis
      resistance, migratory activity and MMP2 expression. Analysis of MAPK signal
      pathways showed that GLUT1 inhibition significantly decreased JNK activation,
      which regulates a wide range of targets in the metastatic cascade. In summary,
      our study provides functional evidence that enhanced GLUT1 expression in melanoma
      cells favors their metastatic behavior. These findings specify GLUT1 as an
      attractive therapeutic target and prognostic marker for this highly aggressive
      tumor. 

PMID- 26293683
TI  - Novel iron-containing phosphate binders for treatment of hyperphosphatemia.
AB  - INTRODUCTION: Hyperphosphatemia is a frequent complication of chronic kidney
      disease and is associated with increased mortality. Despite side effects, risk of
      accumulation and high costs, phosphate binders (PBs) have become the crucial
      cornerstone of therapy. The iron-containing PB sucroferric oxyhydroxide (SO) and
      ferric citrate hydrate (FCH) have entered the market and other candidates are
      prior market entry. AREAS COVERED: A literature search was performed using
      MEDLINE and EMBASE databases to identify references on iron-containing PB with
      particular regard to efficacy, safety and potential benefits. Additional hand
      searches were conducted along with a full-text review of any citation that
      appeared relevant. EXPERT OPINION: On the highly competitive market, where the
      'ideal' PB is still unknown, novel substances that offer clear benefits over
      available drugs are desired. Although SO and FCH showed similar efficacy and
      safety compared to sevelamer, head-to-head studies with lanthanum carbonate are
      absent. Clinical 1-year data in a limited patient cohort suggested improved
      adherence for SO and a large randomized controlled trial showed significant
      reduction in hospitalizations and costs for FCH. Additional large randomized
      controlled trials have now to prove these possible advantages. Cost-effectiveness
      in comparison to other PB and the exclusion of significant harms under long-term
      treatment will determine the future use of both drugs.

PMID- 26293672
TI  - Genomic deletion of chromosome 12p is an independent prognostic marker in
      prostate cancer.
AB  - Deletion of 12p is a recurrent alteration in prostate cancer, but the prevalence
      and clinical consequences of this alteration have not been studied in detail.
      Dual labeling fluorescence in situ hybridization using probes for 12p13 (CDKN1B;
      p27) and centromere 12 as a reference was used to successfully analyze more than
      3700 prostate cancers with clinical follow-up data assembled in a tissue
      microarray format. CDKN1B was selected as a probe because it is located in the
      center of the deletion, which spans > 10 Mb and includes > 50 genes in 80% of
      cancers with 12p deletion. Deletion of 12p was found in 13.7% of cancers and
      included 13.5% heterozygous and 0.2% homozygous deletions. 12p deletion were
      linked to advanced tumor stage (p < 0.0001), high Gleason grade (p < 0.0001),
      rapid tumor cell proliferation (p < 0.0001), lymph node metastasis (p = 0.0004),
      and biochemical recurrence (p = 0.0027). Multivariate analysis including pT stage
      (p < 0.0001), Gleason grade (p < 0.0001), pN status (p = 0.0001), preoperative
      PSA levels (p = 0.0001), and resection margin status (p = 0.0001) revealed an
      independent prognostic value of 12p deletion (p = 0.0014). Deletion of 12p was
      unrelated to the ERG fusion status. Deletion of 12p was only marginally linked to
      reduced p27 expression, which by itself was unrelated to clinical outcome. This
      argues against p27 as the key target gene of 12p deletions. In summary, the
      results of our study demonstrate that 12p deletion is frequent in prostate cancer
      and provides independent prognostic information. 12p deletion analysis alone, or
      in combination with other prognostic parameters may thus have clinical utility. 

PMID- 26293682
TI  - Association between bone indices assessed by DXA, HR-pQCT and QCT scans in post
      menopausal women.
AB  - Quantitative computed tomography (QCT), high-resolution peripheral QCT (HR-pQCT)
      and dual X-ray absorptiometry (DXA) scans are commonly used when assessing bone
      mass and structure in patients with osteoporosis. Depending on the imaging
      technique and measuring site, different information on bone quality is obtained.
      How well these techniques correlate when assessing central as well as distal
      skeletal sites has not been carefully assessed to date. One hundred and twenty
      five post-menopausal women aged 56-82 (mean 63) years were studied using DXA
      scans (spine, hip, whole body and forearm), including trabecular bone score
      (TBS), QCT scans (spine and hip) and HR-pQCT scans (distal radius and tibia).
      Central site measurements of areal bone mineral density (aBMD) by DXA and
      volumetric BMD (vBMD) by QCT correlated significantly at the hip (r = 0.74, p <
      0.01). Distal site measurements of density at the radius as assessed by DXA and
      HR-pQCT were also associated (r = 0.74, p < 0.01). Correlations between distal
      and central site measurements of the hip and of the tibia and radius showed weak
      to moderate correlation between vBMD by HR-pQCT and QCT (r = -0.27 to 0.54). TBS
      correlated with QCT at the lumbar spine (r = 0.35) and to trabecular indices of
      HR-pQCT at the radius and tibia (r = -0.16 to 0.31, p < 0.01). There was moderate
      to strong agreement between measuring techniques when assessing the same skeletal
      site. However, when assessing correlations between central and distal sites, the
      associations were only weak to moderate. Our data suggest that the various
      techniques measure different characteristics of the bone, and may therefore be
      used in addition to rather than as a replacment for imaging in clinical practice.

PMID- 26293684
TI  - A kwashiorkor case due to the use of an exclusive rice milk diet to treat atopic
      dermatitis.
AB  - Although several cases of severe hypoalbuminemia resulting from rice milk have
      been described in the past, today the use of rice milk without nutritional
      counseling to treat eczema is still a continuing, poor practice. We describe a
      kwashiorkor case in an infant with severe eczema exclusively fed with rice milk.
      It is well documented that rice milk is not a sufficient protein source.
      Moreover, only a small portion of eczema is triggered by food allergy. In
      conclusion this case raises the importance of managing dietary changes facing
      food allergies with responsibility for specialized consensus among pediatricians,
      nutritionists, endocrinologists and allergists all of them specialist
      professionals. 

PMID- 26293665
TI  - SNP55, a new functional polymorphism of MDM2-P2 promoter, contributes to allele
      specific expression of MDM2 in endometrial cancers.
AB  - BACKGROUND: The functional single nucleotide polymorphism (SNP) in the MDM2
      promoter region, SNP309, is known to be associated with various diseases,
      particularly cancer. Although many studies have been performed to demonstrate the
      mechanism of allele-specific expression (ASE) on SNP309, they have only utilized
      in vitro techniques. It is unknown whether ASE of MDM2 is ascribed solely to
      SNP309, in vivo. METHODS: We attempted to evaluate ASE of MDM2 in vivo using post
      labeling followed by automated capillary electrophoresis under single-strand
      conformation polymorphism conditions. For measuring a quantitative difference, we
      utilized the SNPs on the exons of MDM2 as markers, the status of which was
      heterozygous in a large population. To address the cause of ASE beyond 20%, we
      confirmed sequences of both MDM2-3'UTR and promoter regions. We assessed the SNP
      which might be the cause of ASE using biomolecular interaction analysis and
      luciferase assay. RESULTS: ASE beyond 20% was detected in endometrial cancers,
      but not in cancer-free endometria samples only when an SNP rs1690916 was used as
      a marker. We suspected that this ASE in endometrial cancer was caused by the
      sequence heterogeneity in the MDM2-P2 promoter, and found a new functional
      polymorphism, which we labelled SNP55. There was no difference between cancer
      free endometria and endometrial cancer samples neither for SNP55 genotype
      frequencies nor allele frequencies, and so, SNP55 alone does not affect
      endometrial cancer risk. The SNP55 status affected the DNA binding affinity of
      transcription factor Sp1 and nuclear factor kappa-B (NFkappaB). Transcriptional
      activity of the P2 promoter containing SNP55C was suppressed by NFkappaB p50
      homodimers, but that of SNP55T was not. Only ASE-positive endometrial cancer
      samples displayed nuclear localization of NFkappaB p50. CONCLUSIONS: Our findings
      suggest that both the SNP55 status and the NFkappaB p50 activity are important in
      the transcriptional regulation of MDM2 in endometrial cancers.

PMID- 26293688
TI  - Change in QRS Morphology during Extrasystole Ablation: What is the Mechanism?

PMID- 26293685
TI  - An empowerment intervention for Indigenous communities: an outcome assessment.
AB  - BACKGROUND: Empowerment programs have been shown to contribute to increased
      empowerment of individuals and build capacity within the community or workplace.
      To-date, the impact of empowerment programs has yet to be quantified in the
      published literature in this field. This study assessed the Indigenous-developed
      Family Wellbeing (FWB) program as an empowerment intervention for a child safety
      workforce in remote Indigenous communities by measuring effect sizes. The study
      also assessed the value of measurement tools for future impact evaluations.
      METHODS: A three-day FWB workshop designed to promote empowerment and workplace
      engagement among child protection staff was held across five remote north
      Queensland Indigenous communities. The FWB assessment tool comprised a set of
      validated surveys including the Growth and Empowerment Measure (GEM), Australian
      Unity Wellbeing Index, Kessler psychological distress scale (K10) and Workforce
      engagement survey. The assessment was conducted pre-intervention and three months
      post-intervention. RESULTS: The analysis of pre-and post-surveys revealed that
      the GEM appeared to be the most tangible measure for detecting positive changes
      in communication, conflict resolution, decision making and life skill
      development. The GEM indicated a 17 % positive change compared to 9 % for the
      Australian Unity Wellbeing Index, 5 % for the workforce engagement survey and
      less than 1 % for K10. CONCLUSIONS: This study extended qualitative research and
      identified the best measurement tool for detecting the outcomes of empowerment
      programs. The GEM was found the most sensitive and the most tangible measure that
      captures improvements in communication, conflict resolution, decision making and
      life skill development. The GEM and Australian Unity Wellbeing Index could be
      recommended as routine measures for empowerment programs assessment among similar
      remote area workforce.

PMID- 26293675
TI  - Molecular and clinical profiles of syndecan-1 in solid and hematological cancer
      for prognosis and precision medicine.
AB  - Syndecan-1 (SDC1, CD138) is a key cell surface adhesion molecule essential for
      maintaining cell morphology and interaction with the surrounding
      microenvironment. Deregulation of SDC1 contributes to cancer progression by
      promoting cell proliferation, metastasis, invasion and angiogenesis, and is
      associated with relapse through chemoresistance. SDC1 expression level is also
      associated with responses to chemotherapy and with prognosis in multiple solid
      and hematological cancers, including multiple myeloma and Hodgkin lymphoma. At
      the tissue level, the expression levels of SDC1 and the released extracellular
      domain of SDC1 correlate with tumor malignancy, phenotype, and metastatic
      potential for both solid and hematological tumors in a tissue-specific manner.
      The SDC1 expression profile varies among cancer types, but the differential
      expression signatures between normal and cancer cells in epithelial and stromal
      compartments are directly associated with aggressiveness of tumors and patient's
      clinical outcome and survival. Therefore, relevant biomarkers of SDC signaling
      may be useful for selecting patients that would most likely respond to a
      particular therapy at the time of diagnosis or perhaps for predicting relapse. In
      addition, the reciprocal expression signature of SDC between tumor epithelial and
      stromal compartments may have synergistic value for patient selection and the
      prediction of clinical outcome. 

PMID- 26293686
TI  - Comparative Assessment of Different Health Utility Measures in Systemic Lupus
      Erythematosus.
AB  - In a time of increasing economic constraints, it is crucial that health systems
      optimize their resource use to ensure that they generate the maximum possible
      health gain. Therefore, it is necessary for health interventions to be evaluated
      and compared across therapeutic boundaries. Undertaking such an evaluation a
      generic utility-based measure is required. But it remains uncertain whether the
      utility values obtained by direct or indirect methods are comparable and which
      approach is the most appropriate in Systemic Lupus Erythematosus (SLE)
      population. In the study, we compared the utility values obtained by an indirect
      method (EQ-5D) with direct utility instruments, the standard gamble (SG) and
      visual analog scale (VAS), in SLE patients. The correlations between VAS, EQ-5D
      and LupusQoL were significant; relative good intraclass correlations or kappa
      coefficients indicated the reliability of these instruments. A model
      incorporating the SLEDAI scores and LupusQoL domains of emotional health and pain
      was a good predictor of VAS. SLEDAI score was a good predictor in the SG
      regression model. These findings suggested that the VAS and EQ-5D might be valid
      and reliable measures to assess health related quality of life in SLE patients
      and represent promising outcome measures for future research in this population. 

PMID- 26293687
TI  - Review article: BK virus in systemic lupus erythematosus.
AB  - BK virus (BKV) is a human polyomavirus with a seroprevalence of 60-80 % in the
      general population. In renal transplant patients, it is known to cause renal
      failure, ureteric stenosis and hemorrhagic cystitis. In bone marrow transplant
      patients, it is evident that BKV can also cause hemorrhagic cystitis along with
      BK virus nephropathy (BKVN) in the native kidneys, with subsequent renal failure.
      However, little is known about BVKN in non-transplanted immune-compromised
      patients, such as systemic lupus erythematosus (SLE) who may have underlying
      nephritis and have a compromised immune system due to therapy and/or systemic
      illness. Thus, this article will focus on the clinical aspects of BKV and its
      association in patients with SLE. 

PMID- 26293689
TI  - Radiation therapy and neutropenia.

PMID- 26293690
TI  - By suppressing the expression of anterior pharynx-defective-1alpha and -1beta and
      inhibiting the aggregation of beta-amyloid protein, magnesium ions inhibit the
      cognitive decline of amyloid precursor protein/presenilin 1 transgenic mice.
AB  - Alzheimer's disease (AD) is associated with a magnesium ion (Mg(2+)) deficit in
      the serum or brain. However, the mechanisms regulating the roles of Mg(2+) in the
      pathologic condition of AD remain unknown. We studied whether brain Mg(2+) can
      decrease beta-amyloid (Abeta) deposition and ameliorate the cognitive decline in
      a model of AD, the APPswe/PS1DE9 transgenic (Tg) mouse. We used a recently
      developed compound, magnesium-L-threonate (MgT), for a treatment that resulted in
      enhanced clearance of Abeta in an anterior pharynx-defective (APH)-1alpha/-1beta
      dependent manner. To further explore how MgT treatment inhibits cognitive decline
      in APP/PS1 Tg mice, the critical molecules for amyloid precursor protein (APP)
      cleavage and signaling pathways were investigated. In neurons, ERK1/2 and
      PPARgamma signaling pathways were activated by MgT treatment, which in turn
      suppressed (by >80%) the expression of APH-1alpha/-1beta, which is responsible
      for the deposition of Abeta and potentially contributes to the memory deficit
      that occurs in AD. More important, Abeta oligomers in the cerebrospinal fluid
      (CSF) further promoted the expression of APH-1alpha/-1beta (by >2.5-fold), which
      enhances the gamma-cleavage of APP and Abeta deposition during AD progression.
      These findings provide new insights into the mechanisms of AD progression and are
      instrumental for developing better strategies to combat the disease.

PMID- 26293692
TI  - Graphene-Based Materials for Lithium-Ion Hybrid Supercapacitors.
AB  - Lithium-ion hybrid supercapacitors (LIHSs), also called Li-ion capacitors, have
      attracted much attention due to the combination of the rapid charge-discharge and
      long cycle life of supercapacitors and the high energy-storage capacity of
      lithium-ion batteries. Thus, LIHSs are expected to become the ultimate power
      source for hybrid and all-electric vehicles in the near future. As an electrode
      material, graphene has many advantages, including high surface area and porous
      structure, high electric conductivity, and high chemical and thermal stability,
      etc. Compared with other electrode materials, such as activated carbon, graphite,
      and metal oxides, graphene-based materials with 3D open frameworks show higher
      effective specific surface area, better control of channels, and higher
      conductivity, which make them better candidates for LIHS applications. Here, the
      latest advances in electrode materials for LIHSs are briefly summarized, with an
      emphasis on graphene-based electrode materials (including 3D graphene networks)
      for LIHS applications. An outlook is also presented to highlight some future
      directions. 

PMID- 26293694
TI  - Sensitive determination of glucose in Dulbecco's modified Eagle medium by high
      performance liquid chromatography with 1-phenyl-3-methyl-5-pyrazolone
      derivatization: application to gluconeogenesis studies.
AB  - A new pre-column derivative high-performance liquid chromatography (HPLC) method
      for determination of d-glucose with 3-O-methyl-d-glucose (3-OMG) as the internal
      standard was developed and validated in order to study the gluconeogenesis in
      HepG2 cells. Samples were derivatized with 1-phenyl-3-methy-5-pyrazolone at 70
      degrees C for 50 min. Glucose and 3-OMG were extracted by liquid-liquid
      extraction and separated on a YMC-Triart C18 column, with a gradient mobile phase
      composed of acetonitrile and 20 mm ammonium acetate solution containing 0.09% tri
      ethylamine at a flow rate of 1.0 mL/min. The eluate were detected using a UV
      detector at 250 nm. The assay was linear over the range 0.39-25 MUm (R(2) =
      0.9997, n = 5) and the lower limit of quantitation was 0.39 MUm (0.070 mg/mL).
      Intra- and inter-day precision and accuracy were <15% and within +/-3%,
      respectively. After validation, the HPLC method was applied to investigate the
      gluconeogenesis in Dulbecco's modified Eagle medium (DMEM) cultured HepG2 cells.
      Glucose concentration was determined to be about 1-2.5 MUm in this
      gluconeogenesis assay. In conclusion, this method has been shown to determine
      small amounts of glucose in DMEM successfully, with lower limit of quantitation
      and better sensitivity when compared with common commercial glucose assay kits.

PMID- 26293693
TI  - Management of Children with Severe, Severe-profound, and Profound Sensorineural
      Hearing Loss.
AB  - Management of children with severe, severe-profound, and profound sensorineural
      hearing loss is best achieved using a family-centered approach by a team of
      health professionals, including audiologists, speech pathologists,
      otolaryngologists, pediatricians, genetic counselors, and early intervention
      programs. Early diagnosis and intervention offers the best chance for speech and
      language acquisition. Although hearing aids can provide some of the needed
      information, they are often not sufficient for spoken language development and a
      cochlear implant is needed. This must be combined with a strong audiology and
      speech therapy rehabilitation program. 

PMID- 26293696
TI  - Reflections on the true nature of spatial clusters in myelodysplastic syndromes.

PMID- 26293697
TI  - Vive la resistance: reviving resistance for 21st century conservation.
AB  - Confronted with increasing anthropogenic change, conservation in the 21st century
      requires a sound understanding of how ecological systems change during
      disturbance. We highlight the benefits of recognizing two distinct components of
      change in an ecological unit (i.e., ecosystem, community, population):
      'resistance', the ability to withstand disturbance; and 'resilience', the
      capacity to recover following disturbance. By adopting a 'resistance-resilience'
      framework, important insights for conservation can be gained into: (i) the key
      role of resistance in response to persistent disturbance, (ii) the intrinsic
      attributes of an ecological unit associated with resistance and resilience, (iii)
      the extrinsic environmental factors that influence resistance and resilience,
      (iv) mechanisms that confer resistance and resilience, (v) the post-disturbance
      status of an ecological unit, (vi) the nature of long-term ecological changes,
      and (vii) policy-relevant ways of communicating the ecological impacts of
      disturbance processes. 

PMID- 26293698
TI  - A Cd(ii) based metal organic framework: a photosensitive current conductor.
AB  - A novel cadmium(ii) based metal organic framework, [Cd(3-bpd)(SCN)2]n () where 3
      bpd = 1,4-bis(3-pyridyl)-2,3-diaza-1,3-butadiene has been synthesized and
      characterized by elemental analysis, various spectroscopic techniques, TGA and
      single crystal X-ray diffraction analysis. X-ray analysis shows the formation of
      an undulated polymeric two-dimensional network parallel to the (0 -1 1) plane.
      Current conduction properties of have been explored in the dark and in the
      presence of light. The study shows that current conduction of the complex
      increases with the increase of the incident light intensity. On progression of
      intensity of glancing radiation the photosensitivity of has been increased. The
      time dependent light response on charge carrier conduction reveals that complex
      may uncover new ground to explore in optoelectronic switching applications. 

PMID- 26293691
TI  - Dynamic subnuclear relocalisation of WRKY40 in response to Abscisic acid in
      Arabidopsis thaliana.
AB  - WRKY18, WRKY40 and WRKY60 are members of the WRKY transcription factor family and
      function as transcriptional regulators in ABA signal transduction in Arabidopsis
      thaliana. Here we show that WRKY18 and WRKY40, but not WRKY60, co-localise with
      PIF3, PIF4 and PHYB to Phytochrome B-containing nuclear bodies (PNBs).
      Localisation to the PNBs is phosphorylation-dependent and is inhibited by the
      general Ser/Thr-kinase inhibitor Staurosporine. Upon ABA treatment, WRKY40
      relocalises from PNBs to the nucleoplasm in an OST1-dependent manner. This
      stimulus-induced relocalisation was not observed in response to other abiotic or
      biotic stimuli, including NaCl, MeJA or flg22 treatment. Bimolecular fluorescence
      complementation experiments indicate that while PIF3, PIF4 and PHYB physically
      interact in these bodies, PHYB, PIF3 and PIF4 do not interact with the two WRKY
      transcription factors, which may suggest a more general role for these bodies in
      regulation of transcriptional activity. 

PMID- 26293695
TI  - Influence of cell polarity on early development of the sea urchin embryo.
AB  - BACKGROUND: Establishment and maintenance of cell polarity is critical for normal
      embryonic development. Previously, it was thought that the echinoderm embryo
      remained relatively unpolarized until the first asymmetric division at the 16
      cell stage. Here, we analyzed roles of the cell polarity regulators, the PAR
      complex proteins, and how their disruption in early development affects later
      developmental milestones. RESULTS: We found that PAR6, aPKC, and CDC42 localize
      to the apical cortex as early as the 2-cell stage and that this localization is
      retained through the gastrula stage. Of interest, PAR1 also colocalizes with
      these apical markers through the gastrula stage. Additionally, PAR1 was found to
      be in complex with aPKC, but not PAR6. PAR6, aPKC, and CDC42 are anchored in the
      cortical actin cytoskeleton by assembled myosin. Furthermore, assembled myosin
      was found to be necessary to maintain proper PAR6 localization through subsequent
      cleavage divisions. Interference with myosin assembly prevented the embryos from
      reaching the blastula stage, while transient disruptions of either actin or
      microtubules did not have this effect. CONCLUSIONS: These observations suggest
      that disruptions of the polarity in the early embryo can have a significant
      impact on the ability of the embryo to reach later critical stages in
      development.

PMID- 26293700
TI  - Examining Nutrition Knowledge of Bariatric Surgery Patients: What Happens to
      Dietary Knowledge over Time?
AB  - BACKGROUND: Nutrition education is a standard of care in bariatric surgery
      clinical practice guidelines. Despite its known importance, no studies have
      documented the trajectory of nutrition knowledge over the course of the bariatric
      surgery process. Primary objectives included determining changes in bariatric
      surgery nutrition knowledge scores from the pre-surgical phase to 1-month post
      surgical intervention and investigating the impact of time on nutrition education
      retention in bariatric patients. Secondary objectives focused on the relationship
      between patients' pre-operative anxiety and depression on nutrition knowledge
      retention. METHODS: Prior to data collection, patients attended a nutrition
      education class and met with a registered dietitian. One hundred and nineteen
      consented patients eligible for bariatric surgery completed a nutrition knowledge
      questionnaire, Eating After Bariatric Surgery (EABS) prior to and 1 month
      following bariatric surgery. RESULTS: Analyses revealed (1) patients' nutrition
      knowledge (measured by EABS) significantly increased from the pre-operative phase
      (M = 46.9; SD = 14.4) to the post-operative phase ((M = 56.9; SD = 14.1), t(118)
      = -8.01, p < .001); (2) time between the nutrition education class and patients'
      surgery significantly impacted knowledge retained; (3) patients with higher pre
      operative levels of depression and anxiety had significantly lower post-operative
      nutrition knowledge; and (4) gender differences in terms of patients' nutrition
      knowledge. CONCLUSIONS: This study confirmed that dietary knowledge significantly
      improves following surgical intervention. Furthermore, increased time in between
      receiving nutrition knowledge and surgery resulted in less retained knowledge 1
      month post-op. Future education interventions for bariatric surgery programs
      should focus on addressing these factors to optimize patient knowledge and
      information retention after surgery.

PMID- 26293701
TI  - Use of a bibliometric literature review to assess medical research capacity in
      post-conflict and developing countries: Somaliland 1991-2013.
AB  - OBJECTIVES: Effective healthcare systems require high-quality research to guide
      evidence-based interventions and strategic planning. In low- and middle-income
      countries, especially those emerging from violent conflict, research capacity
      often lags behind other aspects of health system development. Here, we sought to
      bibliometrically review health-related research output in Somaliland, a post
      conflict self-declared, autonomous nation on the Horn of Africa, as a means of
      assessing research capacity. METHODS: We reviewed articles on health-related
      research conducted in Somaliland between 1991 and 2013 that included a
      description of the experimental design, and articles were published in either a
      peer-reviewed journal or as part of a scholarly programme receiving formal
      review. We did not include policy or social science research that did not enrol
      or interact with subjects from Somaliland. Using online databases, all studies
      meeting minimum eligibility criteria were reviewed in regard to Somaliland-based
      co-authorship, topic of research and specific measures of quality. RESULTS: A
      total of 37 studies were included in this review. Of these, only 19 (51%)
      included co-authorship by Somaliland-based researchers. Of the 21 studies
      reporting ethical approval, 16 (64%) received approval from the Somalia or
      Somaliland Ministry of Health, while five received approval from a university or
      national commission. More than two-thirds of published research was limited to a
      few areas of investigation with most (19, 51%) following basic cross-sectional
      study designs. The number of articles published per year increased from 0 to 1 in
      the years 1991-2007 to a maximum of 8 in 2013. CONCLUSIONS: Research activity in
      Somaliland is extremely limited. Investigators from high-income countries have
      largely directed the research agenda in Somaliland; only half of the included
      studies list co-authors from institutions in Somaliland. Leadership and
      governance of health research in Somaliland is required to define national
      priorities, promote scholarly activity and guide the responsible conduct of
      research. The methods used here to assess research capacity may be generalisable
      to other low- and middle-income countries and post-conflict settings to measure
      the impact of research capacity-building efforts.

PMID- 26293702
TI  - Corrigendum: miR-218 is essential to establish motor neuron fate as a downstream
      effector of Isl1-Lhx3.

PMID- 26293703
TI  - Irrigation fluid extravasation during operative hysteroscopy.

PMID- 26293704
TI  - Factors associated with hospital admission after rotator cuff repair: the role of
      peripheral nerve blockade.
AB  - STUDY OBJECTIVE: The objective was to analyze the impact of a peripheral nerve
      block in addition to general anesthesia on hospital admission after surgical
      rotator cuff repair. DESIGN: This was a population-based outcome study. The cost
      effectiveness of ambulatory rotator cuff repair relies on the discharge of
      patients on the day of surgery. As the impact of a peripheral nerve block in
      addition to general anesthesia on this outcome is unknown, we sought to elucidate
      this subject using population-based data. PATIENTS AND METHODS: Information on
      patients undergoing rotator cuff surgery under general anesthesia with or without
      the addition of a peripheral nerve block (GN vs G) from a retrospective database
      provided by Premier Perspective, Inc, Charlotte, NC (http://www.premierinc.com),
      was analyzed. Using multilevel multivariable regressions, we evaluated the
      independent impact of the type of anesthesia on the outcomes hospital admission,
      combined major complications, and increased hospital costs. RESULTS: We
      identified 27,201 patients who underwent surgical rotator cuff repair.
      Approximately 89% (24,240) of patients were discharged on the day of surgery,
      whereas 11% (2961) were admitted to the hospital. The admission rates for the GN
      group were 9.1% and 11.2% for the G group (P=.0001). The multivariable regression
      models showed that patients with the addition of a peripheral nerve block had 18%
      less risk of being admitted to the hospital (relative risk [RR]=0.82; 95%
      confidence interval [CI], 0.74-0.91; P=.0003) compared with those without this
      intervention. Differences in risk for combined major complications (RR=1.00; 95%
      CI, 0.83-1.20; P=.9751) or increased hospital costs (RR=0.97; 95% CI, 0.93-1.02;
      P=.2538) were nonsignificant. DISCUSSION: For patients undergoing surgical
      rotator cuff repair under general anesthesia, the addition of a peripheral nerve
      block may be associated with a reduction in the need for postoperative hospital
      admission after ambulatory surgery. Although the reason for this finding has to
      remain speculative, better pain control may play a role.

PMID- 26293705
TI  - A Metric for Reducing False Positives in the Computer-Aided Detection of Breast
      Cancer from Dynamic Contrast-Enhanced Magnetic Resonance Imaging Based Screening
      Examinations of High-Risk Women.
AB  - Magnetic resonance imaging (MRI)-enabled cancer screening has been shown to be a
      highly sensitive method for the early detection of breast cancer. Computer-aided
      detection systems have the potential to improve the screening process by
      standardizing radiologists to a high level of diagnostic accuracy. This
      retrospective study was approved by the institutional review board of Sunnybrook
      Health Sciences Centre. This study compares the performance of a proposed method
      for computer-aided detection (based on the second-order spatial derivative of the
      relative signal intensity) with the signal enhancement ratio (SER) on MRI-based
      breast screening examinations. Comparison is performed using receiver operating
      characteristic (ROC) curve analysis as well as free-response receiver operating
      characteristic (FROC) curve analysis. A modified computer-aided detection system
      combining the proposed approach with the SER method is also presented. The
      proposed method provides improvements in the rates of false positive markings
      over the SER method in the detection of breast cancer (as assessed by FROC
      analysis). The modified computer-aided detection system that incorporates both
      the proposed method and the SER method yields ROC results equal to that produced
      by SER while simultaneously providing improvements over the SER method in terms
      of false positives per noncancerous exam. The proposed method for identifying
      malignancies outperforms the SER method in terms of false positives on a
      challenging dataset containing many small lesions and may play a useful role in
      breast cancer screening by MRI as part of a computer-aided detection system. 

PMID- 26293707
TI  - Evaluation of the Toxicity, AChE Activity and DNA Damage Caused by Imidacloprid
      on Earthworms, Eisenia fetida.
AB  - Imidacloprid is a well-known pesticide and it is timely to evaluate its toxicity
      to earthworms (Eisenia fetida). In the present study, the effect of imidacloprid
      on reproduction, growth, acetylcholinesterase (AChE) and DNA damage in earthworms
      was assessed using an artificial soil medium. The median lethal concentration
      (LC50) and the median number of hatched cocoons (EC50) of imidacloprid to
      earthworms was 3.05 and 0.92 mg/kg respectively, the lowest observed effect
      concentration of imidacloprid about hatchability, growth, AChE activity and DNA
      damage was 0.02, 0.5, 0.1 and 0.5 mg/kg, respectively. 

PMID- 26293708
TI  - Demonstrating correction of low levels of astigmatism with realistic scenes.
AB  - PURPOSE AND METHOD: Modern standard visual acuity tests are primarily designed as
      diagnostic tools for use during subjective refraction and normally bear little
      relation to real-world situations. We have developed a methodology to create
      realistic rendered scenes that demonstrate potential vision improvement in a
      relevant and engaging way. Low-cylindrical refractive error can be made more
      noticeable by optimizing the contrast and spatial frequencies, and by testing
      four different visual perception skills: motion tracking, pattern recognition,
      visual clutter differentiation and contrast sensitivity. Using a 1.00DC lens
      during iteration, we created a range of still and video scenes before optimizing
      to a selection 3-D rendered street scenes. These were assessed on everyday
      relevance, emotional and visual engagement and sensitivity to refractive
      correction for low-cylinder astigmats (0.75-1.00DC, n=74) wearing best spherical
      equivalent correction and then with astigmatism corrected. RESULTS AND
      CONCLUSIONS: The most promising visual elements involved or combined optimized
      textures, distracting patterns behind text, faces at a distance, and oblique
      text. 91.9% of subjects (95% CI: 83.2, 97.0) reported an overall visual
      improvement when viewing the images with astigmatic correction, and 96% found the
      images helpful to determine which type of contact lens to use. Our method, which
      combines visual science with design thinking, takes a new approach to creating
      vision tests. The resultant test scenes can be used to improve patient
      interaction and help low cylinder astigmats see relevant, every-day benefits in
      correcting low levels (0.75 & 1.00DC) of astigmatism.

PMID- 26293709
TI  - Fractal dimension (df) as a new structural biomarker of clot microstructure in
      different stages of lung cancer.
AB  - Venous thromboembolism (VTE) is common in cancer patients, and is the second
      commonest cause of death associated with the disease. Patients with chronic
      inflammation, such as cancer, have been shown to have pathological clot
      structures with modulated mechanical properties. Fractal dimension (df) is a new
      technique which has been shown to act as a marker of the microstructure and
      mechanical properties of blood clots, and can be performed more readily than
      current methods such as scanning electron microscopy (SEM). We measured df in 87
      consecutive patients with newly diagnosed lung cancer prior to treatment and 47
      matched-controls. Mean group values were compared for all patients with lung
      cancer vs controls and for limited disease vs extensive disease. Results were
      compared with conventional markers of coagulation, fibrinolysis and SEM images.
      Significantly higher values of df were observed in lung cancer patients compared
      with controls and patients with extensive disease had higher values than those
      with limited disease (p< 0.05), whilst conventional markers failed to distinguish
      between these groups. The relationship between df of the incipient clot and
      mature clot microstructure was confirmed by SEM and computational modelling:
      higher df was associated with highly dense clots formed of smaller fibrin fibres
      in lung cancer patients compared to controls. This study demonstrates that df is
      a sensitive technique which quantifies the structure and mechanical properties of
      blood clots in patients with lung cancer. Our data suggests that df has the
      potential to identify patients with an abnormal clot microstructure and greatest
      VTE risk. 

PMID- 26293710
TI  - Refractory primary medication nonadherence: Prevalence and predictors after
      pharmacist counseling at hospital discharge.
AB  - Successful secondary prevention of cardiovascular disease relies on medication
      therapy; thus, minimizing nonadherence is a focus for improving patient outcomes.
      Receipt of discharge medication counseling has been associated with improved drug
      knowledge and adherence. We evaluated the prevalence and predictors of
      postdischarge primary nonadherence (not filling new prescriptions) in patients
      who received discharge medication counseling by a pharmacist (ie, refractory to
      intervention) as part of a randomized controlled trial. Of 341 patients, 9.4% of
      patients did not fill all prescriptions after discharge. Patients who were living
      alone were more likely to not fill their medications compared to those who were
      married or cohabitating (odds ratio [OR]: 2.2, 95% confidence interval [CI]: 1.01
      4.8, P = 0.047). Patients who were discharged with greater than 10 medications
      were also more likely to demonstrate primary nonadherence (OR: 2.3, 95% CI: 1.05
      4.98, P = 0.036). Patients with lower income were less likely to fill
      prescriptions in univariate analysis (P = 0.04) but not multivariable analysis.
      Our study demonstrates that among patients hospitalized for acute cardiovascular
      events, primary medication nonadherence persisted despite discharge medication
      counseling. Targeted or multimodal approaches that address patient-specific
      barriers, such as cost, social isolation, and polypharmacy, in addition to
      discharge counseling, may further facilitate adherence.

PMID- 26293711
TI  - Venous thromboembolism prophylaxis during and following caesarean section: a
      survey of clinical practice.
AB  - BACKGROUND: Caesarean section (CS) is a significant risk factor for venous
      thromboembolism; however, the optimal method of thromboprophylaxis around the
      time of CS is unknown. AIMS: To examine current thromboprophylaxis practice
      during and following CS in Australia and New Zealand, and the willingness of
      obstetricians to participate in a randomised controlled trial (RCT) comparing
      different methods of thromboprophylaxis after CS. MATERIALS AND METHODS: An
      online survey was sent to fellows and trainees of the Royal Australian and New
      Zealand College of Obstetricians and Gynaecologists. RESULTS: There were 488
      responses from currently practising obstetricians (response rate 23.4%). During
      CS, 48% and 80% of obstetricians recommended intermittent pneumatic compression
      (IPC) and elastic stockings (ES), respectively. Following CS, 96-97% of
      obstetricians recommended early ambulation, 87-90% recommended ES, 23-36%
      recommended IPC, and 42-65% recommended low molecular weight heparin (LMWH)
      depending on clinical factors. Increased BMI (OR 3.42; 95% CI 2.87-4.06),
      emergency CS (OR 1.88; 95% CI 1.67-2.16) and older maternal age (OR 1.37; 95% CI
      1.26-1.49) were associated with more frequent LMWH use. Of obstetricians who
      prescribed LMWH, 70% adjusted the dose depending on maternal weight. LMWH therapy
      was most commonly recommended until discharge from hospital (31%), <5 days (24%)
      and 5-7 days (15%). Most obstetricians (58-79%) were willing to enrol women in a
      RCT, but less likely if the woman had an increased BMI or emergency CS.
      CONCLUSIONS: There is considerable variation in clinical practice regarding
      thromboprophylaxis during and following CS. Obstetricians support a RCT to assess
      different methods of thromboprophylaxis following CS.

PMID- 26293740
TI  - Large epidemic thresholds emerge in heterogeneous networks of heterogeneous
      nodes.
AB  - One of the famous results of network science states that networks with
      heterogeneous connectivity are more susceptible to epidemic spreading than their
      more homogeneous counterparts. In particular, in networks of identical nodes it
      has been shown that network heterogeneity, i.e. a broad degree distribution, can
      lower the epidemic threshold at which epidemics can invade the system. Network
      heterogeneity can thus allow diseases with lower transmission probabilities to
      persist and spread. However, it has been pointed out that networks in which the
      properties of nodes are intrinsically heterogeneous can be very resilient to
      disease spreading. Heterogeneity in structure can enhance or diminish the
      resilience of networks with heterogeneous nodes, depending on the correlations
      between the topological and intrinsic properties. Here, we consider a plausible
      scenario where people have intrinsic differences in susceptibility and adapt
      their social network structure to the presence of the disease. We show that the
      resilience of networks with heterogeneous connectivity can surpass those of
      networks with homogeneous connectivity. For epidemiology, this implies that
      network heterogeneity should not be studied in isolation, it is instead the
      heterogeneity of infection risk that determines the likelihood of outbreaks. 

PMID- 26293741
TI  - HSP-90 expression as a predictor of response to radiotherapy in head and neck
      cancer patients.
AB  - INTRODUCTION AND OBJECTIVES: HSP-90 is an intracellular protein that protects the
      cell from environmental stress situations. The overexpression of HSP-90 isoforms
      could serve as a mechanism of resistance to radiotherapy for tumour cells. We
      studied this effect in a sample of head and neck tumours. METHODS: We included 87
      patients diagnosed with oral cavity, oropharynx, larynx and hypopharynx tumours.
      We studied the expression of the HSP-90 isoforms by real-time PCR on pre
      treatment biopsy samples. We analysed the relationship between HSP-90 expression
      levels and local relapse of the tumour with CRT decision trees. RESULTS: The
      expression levels of the inducible citosolic isoform (HSP90AA) allowed the
      definition of 2 groups of patients with different rates of local relapse. The
      group with a low expression level showed a 2.9% local relapse rate, while the
      group with a high expression level showed a 38.2% rate. Survival curves showed
      differences in time to local relapse for both groups of patients. These
      differences did not reach statistical significance. CONCLUSIONS: Radiotherapy
      response was related to expression levels of HSP-90 in a sample of head and neck
      cancer patients. This result could prove useful in the selection of treatments
      for this group of patients.

PMID- 26293742
TI  - Safety of Methylphenidate and Atomoxetine in Children with Attention
      Deficit/Hyperactivity Disorder (ADHD): Data from the Italian National ADHD
      Registry.
AB  - OBJECTIVE: The aim of this study was to assess the type and frequency of adverse
      events (AEs) in children with attention-deficit/hyperactivity disorder (ADHD)
      treated with methylphenidate or atomoxetine over a 5-year period in a large
      naturalistic study. METHODS: We draw on data from the Italian ADHD Registry, a
      national database for postmarketing phase IV pharmacovigilance of ADHD
      medications across 90 centers. AEs were defined as severe or mild as per the
      classification of the Italian Medicines Agency. AE frequency in the two treatment
      groups was compared using incidence rates per 100 person-years (IR100PY) and
      incidence rate ratios (IRRs). Mantel-Haenszel adjusted IRRs were calculated to
      control for psychiatric comorbidity. RESULTS: A total of 1350 and 753
      participants (aged 6-18 years, mean age 10.7 +/- 2.8) were treated with
      methylphenidate and atomoxetine, respectively, from 2007 to 2012. Ninety
      participants (7 %) were switched from methylphenidate to atomoxetine, and 138 (18
      %) from atomoxetine to methylphenidate. Thirty-seven children treated with
      atomoxetine and 12 with methylphenidate had their medication withdrawn. Overall,
      645 patients (26.8 %) experienced at least one mild AE (including decreased
      appetite and irritability, for both drugs) and 95 patients (3.9 %) experienced at
      least one severe AE (including severe gastrointestinal events). IR100PY were
      significantly higher in the atomoxetine-treated group compared with the
      methylphenidate-treated group for a number of mild and severe AEs and for any
      severe or mild AEs. After controlling for comorbidities, IRR was still
      significantly higher in the atomoxetine group compared with the methylphenidate
      group for a number of mild (decreased appetite, weight loss, abdominal pain,
      dyspepsia, stomach ache, irritability, mood disorder and dizziness) and severe
      (gastrointestinal, neuropsychiatric, and cardiovascular) AEs. CONCLUSIONS: In
      this naturalistic study, methylphenidate had a better safety profile than
      atomoxetine.

PMID- 26293743
TI  - Network Meta-Analysis and Cost-Effectiveness Analysis of New Generation
      Antidepressants.
AB  - BACKGROUND: Major depressive disorder (MDD) impacts health, quality of life and
      workplace productivity. Antidepressant treatment is the primary therapeutic
      intervention. This study assessed the efficacy and tolerability of new generation
      antidepressants and their cost-effectiveness in the Singapore healthcare system.
      METHODS: We conducted a systematic search for head-to-head randomised controlled
      trials on ten antidepressants (agomelatine, duloxetine, escitalopram,
      fluvoxamine, fluoxetine, mirtazapine, paroxetine, sertraline, trazodone and
      venlafaxine) employed as monotherapy in acute MDD management. We performed a
      network meta-analysis to compare their relative efficacy. The outcome measures
      for efficacy were response and remission rate, and mean change in Hamilton
      Depression Rating Scale (HDRS) score; and for tolerability, study withdrawal
      rates due to adverse events. To evaluate their relative cost effectiveness, a
      decision tree simulating a cohort of MDD patients using antidepressant as
      monotherapy was constructed from a societal perspective over 6 months. We used
      effectiveness data from our network meta-analysis and local data on resource use
      for depression in Singapore. The incremental cost expected for each additional
      quality-adjusted life-year (QALY) gained was calculated and presented as the
      incremental cost-effectiveness ratio (ICER). RESULTS: We identified 76 relevant
      articles for the network meta-analysis. Of the ten agents included in the
      analysis, mirtazapine and agomelatine were most efficacious in achieving response
      and remission, respectively. Mirtazapine and duloxetine resulted in the greatest
      magnitude of change in the HDRS score. Agomelatine, escitalopram and sertraline
      were the best tolerated of the drugs analysed, while duloxetine was the least
      well tolerated drug. Using a composite outcome of efficacy (response and
      remission rates) and tolerability, agomelatine, escitalopram and mirtazapine were
      the favoured treatments. In the cost-effectiveness analysis, apart from
      agomelatine, all the treatments were dominated by mirtazapine. Against
      mirtazapine, agomelatine was not cost effective given that its ICER exceeded the
      threshold value. CONCLUSION: Agomelatine, escitalopram and mirtazapine had
      favourable balance between efficacy and tolerability. In addition, mirtazapine
      was a cost-effective option in the Singapore healthcare system.

PMID- 26293746
TI  - Erratum to: Oxycodone/Naloxone PR: A Review in Severe Refractory Restless Legs
      Syndrome.

PMID- 26293745
TI  - A Common Reference-Based Indirect Comparison Meta-Analysis of Buccal versus
      Intranasal Midazolam for Early Status Epilepticus.
AB  - BACKGROUND: Intranasal and buccal midazolam have recently emerged as possible
      alternatives to intravenous or rectal diazepam or intravenous lorazepam in the
      treatment of early status epilepticus (SE). However, to date no randomized
      controlled trial (RCT) has directly compared intranasal midazolam with buccal
      midazolam. OBJECTIVE: The aim of this study was to indirectly compare intranasal
      midazolam with buccal midazolam in the treatment of early SE using common
      reference-based indirect comparison meta-analyses. METHODS: RCTs comparing
      intranasal or buccal midazolam versus either intravenous or rectal diazepam for
      early SE were systematically searched. Random-effects Mantel-Haenszel meta
      analyses were performed to obtain odds ratios (ORs) for the efficacy and safety
      of intranasal or buccal midazolam versus either intravenous or rectal diazepam.
      Adjusted indirect comparisons were then made between intranasal and buccal
      midazolam using the obtained results. RESULTS: Fifteen studies, with a total of
      1662 seizures in 1331 patients (some studies included patients with more than one
      episode of SE) were included; 1303 patients were younger than 16 years. Indirect
      comparisons showed no difference between intranasal and buccal midazolam for
      seizure cessation (OR 0.98, 95% CI 0.32-3.01, comparator: intravenous diazepam;
      OR 0.87, 95% CI 0.46-1.64, comparator: rectal diazepam). For serious adverse
      effects, we found a large width and asymmetrical distribution of confidence
      intervals around the obtained OR of 2.81 (95% CI 0.39-20.12; comparator: rectal
      diazepam). No data were available for OR using intravenous diazepam as the
      comparator. CONCLUSIONS: Indirect comparisons suggest that intranasal and buccal
      midazolam share similar efficacy in the treatment of early SE in children.
      Intranasal midazolam should be used with caution and under clinical monitoring of
      vital functions. RCTs directly comparing intranasal midazolam with buccal
      midazolam are required to confirm these findings.

PMID- 26293747
TI  - The Utility of Repeating Automated Blood Pressure Measurements in the Primary
      Care Office.

PMID- 26293744
TI  - The Use of Continuous Treatment Versus Placebo or Intermittent Treatment
      Strategies in Stabilized Patients with Schizophrenia: A Systematic Review and
      Meta-Analysis of Randomized Controlled Trials with First- and Second-Generation
      Antipsychotics.
AB  - BACKGROUND: Although continuous treatment with antipsychotics is still
      recommended as the gold standard treatment paradigm for all patients with
      schizophrenia, some clinicians question whether continuous antipsychotic
      treatment is necessary, or even justified, for every patient with schizophrenia
      who has been stabilized on antipsychotics. OBJECTIVE: The primary objectives of
      this systematic review and meta-analysis were (i) to compare
      relapse/hospitalization risks of stabilized patients with schizophrenia under
      active versus intermittent or placebo treatment conditions; (ii) to examine the
      role of several study characteristics, possibly intervening in the relationship
      between relapse risk and treatment condition; and (iii) to examine whether time
      to relapse is associated with antipsychotic treatment duration. METHODS: A
      systematic literature search, using the MEDLINE database (1950 until November
      2014), was conducted for English-language published randomized controlled trials,
      covering a follow-up time period of at least 6 months, and investigating
      relapse/rehospitalization and/or time-to-relapse rates with placebo or
      intermittent treatment strategies versus continuous treatment with oral and long
      acting injectable first- or second-generation antipsychotics (FGAs/SGAs) in
      stabilized patients with schizophrenia. Additional studies were identified
      through searches of reference lists of other identified systematic reviews and
      Cochrane reports. Two meta-analyses (placebo versus continuous and intermittent
      versus continuous treatment) were performed to obtain an optimal estimation of
      the relapse/hospitalization risks of stabilized patients with schizophrenia under
      these treatment conditions and to assess the role of study characteristics. For
      time-to-relapse data, a descriptive analysis was performed. RESULTS: Forty-eight
      reports were selected as potentially eligible for our meta-analysis. Of these, 21
      met the inclusion criteria. Twenty-five records, identified through Cochrane and
      other systematic reviews and fulfilling the inclusion criteria, were added,
      resulting in a total of 46 records. Stabilized patients with schizophrenia who
      have been exposed for at least 6 months to intermittent or placebo strategies,
      respectively, have a 3 (odds ratio [OR] 3.36; 95% CI 2.36-5.45; p < 0.0001) to 6
      (OR 5.64; 95% CI 4.47-7.11; p < 0.0001) times increased risk of relapse, compared
      with patients on continuous treatment. The availability of rescue medication (p =
      0.0102) was the only study characteristic explaining systematic differences in
      the OR for relapse between placebo versus continuous treatment across studies.
      Studies reporting time-to-relapse data show that the time to (impending) relapse
      is always significantly delayed with continuous treatment, compared with placebo
      or intermittent treatment strategies. Although the interval between treatment
      discontinuation and symptom recurrence can be highly variable, mean time-to
      relapse data seem to indicate a failure of clinical stability before 7-14 months
      with intermittent and before 5 months with placebo treatment strategies. For all
      reports included in this systematic review, median time-to-relapse rates in the
      continuous treatment group were not estimable as <50% of the patients in this
      treatment condition relapsed before the end of the study. CONCLUSIONS: With
      continuous treatment, patients have a lower risk of relapse and remain relapse
      free for a longer period of time compared with placebo and intermittent treatment
      strategies. Moreover, 'success rates' in the intermittent treatment conditions
      are expected to be an overestimate of actual outcome rates. Therefore, continuous
      treatment remains the 'gold standard' for good clinical practice, particularly
      as, until now, only a few and rather general valid predictors for relapse in
      schizophrenia are known and subsequent relapses may contribute to functional
      deterioration as well as treatment resistance in patients with schizophrenia.

PMID- 26293748
TI  - Enzymatic characterization and gene identification of aconitate isomerase, an
      enzyme involved in assimilation of trans-aconitic acid, from Pseudomonas sp. WU
      0701.
AB  - trans-Aconitic acid is an unsaturated organic acid that is present in some plants
      such as soybean and wheat; however, it remains unclear how trans-aconitic acid is
      degraded and/or assimilated by living cells in nature. From soil, we isolated
      Pseudomonas sp. WU-0701 assimilating trans-aconitic acid as a sole carbon source.
      In the cell-free extract of Pseudomonas sp. WU-0701, aconitate isomerase (AI; EC
      5.3.3.7) activity was detected. Therefore, it seems likely that strain
      Pseudomonas sp. WU-0701 converts trans-aconitic acid to cis-aconitic acid with
      AI, and assimilates this via the tricarboxylic acid cycle. For the
      characterization of AI from Pseudomonas sp. WU-0701, we performed purification,
      determination of enzymatic properties and gene identification of AI. The
      molecular mass of AI purified from cell-free extract was estimated to be ~ 25 kDa
      by both SDS/PAGE and gel filtration analyses, indicating that AI is a monomeric
      enzyme. The optimal pH and temperature of purified AI for the reaction were 6.0 
      degrees C and 37  degrees C, respectively. The gene ais encoding AI was cloned on
      the basis of the N-terminal amino acid sequence of the protein, and Southern blot
      analysis revealed that only one copy of ais is located on the bacterial genome.
      The gene ais contains an ORF of 786 bp, encoding a polypeptide of 262 amino
      acids, including the N-terminal 22 amino acids as a putative periplasm-targeting
      signal peptide. It is noteworthy that the amino acid sequence of AI shows 90% and
      74% identity with molybdenum ABC transporter substrate-binding proteins of
      Pseudomonas psychrotolerans and Xanthomonas albilineans, respectively. This is
      the first report on purification to homogeneity, characterization and gene
      identification of AI. DATABASE: The nucleotide sequence of ais described in this
      article is available in the DDBJ/EMBL/GenBank nucleotide sequence databases under
      the Accession No. LC010980.

PMID- 26293749
TI  - Gender Differences Related to Attitudes Toward Suicide and Suicidal Behavior.
AB  - This descriptive study examined gender differences related to attitudes toward
      suicide among randomly selected urban residents. Data was collected using a
      standardized questionnaire through face-to-face interview. Our findings revealed
      that men hold more pro preventive attitudes to help persons with suicidal
      thoughts (80.3 %, p = 0.05) and agreed that suicidal attempts are impulsive (78.6
      %, p = 0.01). However, they hold permissive attitude to help persons with
      incurable diseases and expressing death wishes to die (66 %, p = 0.05). A
      majority of men (78.6 %) than women agreed that "suicidal attempt is essentially
      a cry for help" (chi (2) = 11.798, p = 0.05). These gender differences need to be
      taken into consideration when developing appropriate programs to prevent suicide.
      Further, decriminalizing the law, high-quality research and raising awareness
      about suicide prevention among the general population is crucial in developing
      countries like India. 

PMID- 26293750
TI  - Predictors of Outreach Meetings Among Substance Using Homeless Youth.
AB  - Homeless youth have high rates of substance use and often lack connection to
      social services. Outreach is critical for connecting youth to services, but
      factors influencing their outreach engagement are unknown. This study examined
      predictors of meetings with outreach workers among 79 non-service connected,
      substance using homeless youth between 14 and 24 years of age. Results provide
      direction to service providers in that older age, higher levels of depressive
      symptoms, fewer drug-related problems, and no use of hard drugs within the prior
      30 days predicted higher meeting attendance. Future research is needed testing
      strategies that overcome barriers to outreach engagement.

PMID- 26293751
TI  - Multiple myeloma and bone marrow mesenchymal stem cells' crosstalk: Effect on
      translation initiation.
AB  - Multiple myeloma (MM) malignant plasma cells reside in the bone marrow (BM) and
      convert it into a specialized pre-neoplastic niche that promotes the
      proliferation and survival of the cancer cells. BM resident mesenchymal stem
      cells (BM-MSCs) are altered in MM and in vitro studies indicate their
      transformation by MM proximity is within hours. The response time frame suggested
      that protein translation may be implicated. Thus, we assembled a co-culture model
      of MM cell lines with MSCs from normal donors (ND) and MM patients to test our
      hypothesis. The cell lines (U266, ARP-1) and BM-MSCs (ND, MM) were harvested
      separately after 72 h of co-culture and assayed for proliferation, death, levels
      of major translation initiation factors (eIF4E, eIF4GI), their targets, and
      regulators. Significant changes were observed: BM-MSCs (ND and MM) co-cultured
      with MM cell lines displayed elevated proliferation and death as well as
      increased expression/activity of eIF4E/eIF4GI; MM cell lines co-cultured with MM
      MSCs also displayed higher proliferation and death rates coupled with augmented
      translation initiation factors; in contrast, MM cell lines co-cultured with ND
      MSCs did not display elevated proliferation only death and had no changes in
      eIF4GI levels/activity. eIF4E expression was increased in one of the cell lines.
      Our study demonstrates that there is direct dialogue between the MM and BM-MSCs
      populations that includes translation initiation manipulation and critically
      affects cell fate. Future research should be aimed at identifying therapeutic
      targets that may be used to minimize the collateral damage to the cancer
      microenvironment and limit its recruitment into the malignant process. (c) 2015
      Wiley Periodicals, Inc.

PMID- 26293753
TI  - Ecological interactions on macroevolutionary time scales: clams and brachiopods
      are more than ships that pass in the night.
AB  - Competition among organisms has ecological and evolutionary consequences.
      However, whether the consequences of competition are manifested and measureable
      on macroevolutionary time scales is equivocal. Marine bivalves and brachiopods
      have overlapping niches such that competition for food and space may occur.
      Moreover, there is a long-standing debate over whether bivalves outcompeted
      brachiopods evolutionarily, because brachiopod diversity declined through time
      while bivalve diversity increased. To answer this question, we estimate the
      origination and extinction dynamics of fossil marine bivalve and brachiopod
      genera from the Ordovician through to the Recent while simultaneously accounting
      for incomplete sampling. Then, using stochastic differential equations, we assess
      statistical relationships among diversification and sampling dynamics of
      brachiopods and bivalves and five paleoenvironmental proxies. None of these
      potential environmental drivers had any detectable influence on brachiopod or
      bivalve diversification. In contrast, elevated bivalve extinction rates causally
      increased brachiopod origination rates, suggesting that bivalves have suppressed
      brachiopod evolution. 

PMID- 26293752
TI  - Amelioration of experimentally induced diabetic nephropathy and renal damage by
      nilotinib.
AB  - Diabetes mellitus is an ever growing world-wide health problem. The patient has
      to stick to a firm life-long therapeutic regimen, otherwise diabetic
      complications will develop. Diabetic nephropathy (DN) is one of the most common
      diabetic complications and it requires careful medical attendance. Nilotinib
      hydrochloride is a protein tyrosine kinase inhibitor reported to have numerous
      therapeutic efficacies besides being an anticancer. In the current study, single
      I.P. streptozotocin (50 mg/kg) injection was used to induce type I diabetes
      mellitus in male Sprague-Dawley rats. After 8 weeks, significant deterioration of
      renal function with urinary excretion of nephrin, podocalyxin, and albumin was
      observed. Daily oral administration of nilotinib (20 mg/kg) for 8 weeks
      significantly improved signs of DN on all investigated scales. On a biochemical
      scale, kidney functions, albuminuria, urinary nephrin, podocalyxin excretion, and
      host oxidant/antioxidant balance significantly improved. Kidney content of nitric
      oxide, expression of toll-like receptors 4 and NF-kappaB/p65 activity
      significantly declined as well. On a histopathological scale, alpha-smooth muscle
      actin and nestin expression significantly declined. Meanwhile, area of fibrosis
      significantly declined as seen with significant reduction in accumulation of
      extracellular matrix components and kidney content of collagen. Ultimately, such
      improvements were accompanied by significant restoration of normal kidney
      physiology and function. In conclusion, nilotinib can hinder progression of DN
      through various mechanisms. Reduction of oxidative stress, enhancement of host
      antioxidant defense system, reduction of inflammation, angiogenesis, tissue
      hypoxia, and pro-fibrogenic biomarker expression can be implicated in the
      beneficial therapeutic outcome observed with nilotinib therapy.

PMID- 26293754
TI  - A Web Based Cardiovascular Disease Detection System.
AB  - Cardiovascular Disease (CVD) is one of the most catastrophic and life threatening
      health issue nowadays. Early detection of CVD is an important solution to reduce
      its devastating effects on health. In this paper, an efficient CVD detection
      algorithm is identified. The algorithm uses patient demographic data as inputs,
      along with several ECG signal features extracted automatically through signal
      processing techniques. Cross-validation results show a 98.29 % accuracy for the
      decision tree classification algorithm. The algorithm has been integrated into a
      web based system that can be used at anytime by patients to check their heart
      health status. At one end of the system is the ECG sensor attached to the
      patient's body, while at the other end is the detection algorithm. Communication
      between the two ends is done through an Android application. 

PMID- 26293755
TI  - Perinatal mental health: Fathers - the (mostly) forgotten parent.
AB  - INTRODUCTION: The importance of parental mental health as a determinant of infant
      and child outcomes is increasingly acknowledged. Yet, there is limited
      information regarding paternal mental health during the perinatal period. The aim
      of this review is to summarize existing clinical research regarding paternal
      mental health in the perinatal period in various contexts, and its possible
      impact on infant development. METHOD: An electronic literature search was
      conducted using MEDLINE and PubMed databases. Key texts were used to cross-check
      for any further articles of interest. RESULTS: Men are at increased risk of
      mental health problems during the transition to fatherhood, as well as during the
      perinatal period. Paternal mental health during the perinatal period has been
      shown to impact on their child's emotional and behavioral development. However,
      research addressing the needs of fathers with mental illness and the impact of
      their illness on their infant and family has been limited. CONCLUSIONS: A
      paradigm shift is required, from a focus on women following childbirth and women
      with pre-existing psychiatric disorders, to a broader family perspective with the
      focus firmly on parent-infant relationships. This paradigm shift needs to involve
      greater research into the fathering role and paternal mental illness during the
      perinatal period, including further studies into risk factors, impact on the
      family system, and the most appropriate form of intervention and service
      provision.

PMID- 26293756
TI  - Physiological Growth, Remodeling Potential, and Preserved Function of a Novel
      Bioprosthetic Tricuspid Valve: Tubular Bioprosthesis Made of Small Intestinal
      Submucosa-Derived Extracellular Matrix.
AB  - BACKGROUND: Prosthetic valves currently used in children lack the ability to grow
      with the patient and often require multiple reoperations. Small intestinal
      submucosa-derived extracellular matrix (SIS-ECM) has been used successfully as a
      patch for repair in various tissues, including vessels, valves, and myocardium.
      OBJECTIVES: This study sought to assess the remodeling potential of a tubular
      tricuspid valve (TV) bioprosthesis made of SIS-ECM by evaluating its growth,
      structure, and function in a growing ovine model. METHODS: A total of 12 3-month
      old lambs were studied for a period of 3 or 8 months. SIS-ECM TVs were placed in
      8 lambs; conventional bioprosthetic valves and native valves (NV) were studied as
      controls. All lambs underwent serial echocardiography, measuring annulus diameter
      and valve and right ventricular function. RESULTS: The SIS-ECM valves
      demonstrated an incremental increase in annular diameter similar to NV. SIS-ECM
      valve function was normal in 7 of 8; 1 valve had severe regurgitation due to a
      flail leaflet. Explanted SIS-ECM valves approximated native tissue in gross
      appearance. Histopathology demonstrated migration of resident mesenchymal cells
      into the scaffold and trilaminar ECM organization similar to an NV, without
      inflammation or calcification at 8 months. Ex vivo mechanical testing of SIS-ECM
      valve tissue showed normalization of the elastic modulus by 8 months.
      CONCLUSIONS: In an ovine model, tubular SIS-ECM TV bioprostheses demonstrate
      "growth" and a cell-matrix structure similar to mature NVs while maintaining
      normal valve function. The SIS-ECM valve may provide a novel solution for TV
      replacement in children and adults.

PMID- 26293757
TI  - In Search of Living Valve Substitutes.

PMID- 26293759
TI  - Fate Versus Flow: Wall Shear Stress in the Aortopathy Associated With Bicuspid
      Aortic Valves.

PMID- 26293758
TI  - Valve-Related Hemodynamics Mediate Human Bicuspid Aortopathy: Insights From Wall
      Shear Stress Mapping.
AB  - BACKGROUND: Suspected genetic causes for extracellular matrix (ECM) dysregulation
      in the ascending aorta in patients with bicuspid aortic valves (BAV) have
      influenced strategies and thresholds for surgical resection of BAV aortopathy.
      Using 4-dimensional (4D) flow cardiac magnetic resonance imaging (CMR), we have
      documented increased regional wall shear stress (WSS) in the ascending aorta of
      BAV patients. OBJECTIVES: This study assessed the relationship between WSS and
      regional aortic tissue remodeling in BAV patients to determine the influence of
      regional WSS on the expression of ECM dysregulation. METHODS: BAV patients (n =
      20) undergoing ascending aortic resection underwent pre-operative 4D flow CMR to
      regionally map WSS. Paired aortic wall samples (i.e., within-patient samples
      obtained from regions of elevated and normal WSS) were collected and compared for
      medial elastin degeneration by histology and ECM regulation by protein
      expression. RESULTS: Regions of increased WSS showed greater medial elastin
      degradation compared to adjacent areas with normal WSS: decreased total elastin
      (p = 0.01) with thinner fibers (p = 0.00007) that were farther apart (p = 0.001).
      Multiplex protein analyses of ECM regulatory molecules revealed an increase in
      transforming growth factor beta-1 (p = 0.04), matrix metalloproteinase (MMP)-1 (p
      = 0.03), MMP-2 (p = 0.06), MMP-3 (p = 0.02), and tissue inhibitor of
      metalloproteinase-1 (p = 0.04) in elevated WSS regions, indicating ECM
      dysregulation in regions of high WSS. CONCLUSIONS: Regions of increased WSS
      correspond with ECM dysregulation and elastic fiber degeneration in the ascending
      aorta of BAV patients, implicating valve-related hemodynamics as a contributing
      factor in the development of aortopathy. Further study to validate the use of 4D
      flow CMR as a noninvasive biomarker of disease progression and its ability to
      individualize resection strategies is warranted.

PMID- 26293761
TI  - New Insights and Clarity for Peripartum Heart Failure and Recovery in the Modern
      Era.

PMID- 26293760
TI  - Clinical Outcomes for Peripartum Cardiomyopathy in North America: Results of the
      IPAC Study (Investigations of Pregnancy-Associated Cardiomyopathy).
AB  - BACKGROUND: Peripartum cardiomyopathy (PPCM) remains a major cause of maternal
      morbidity and mortality. OBJECTIVES: This study sought to prospectively evaluate
      recovery of the left ventricular ejection fraction (LVEF) and clinical outcomes
      in the multicenter IPAC (Investigations of Pregnancy Associated Cardiomyopathy)
      study. METHODS: We enrolled and followed 100 women with PPCM through 1 year post
      partum. The LVEF was assessed by echocardiography at baseline and at 2, 6, and 12
      months post-partum. Survival free from major cardiovascular events (death,
      transplantation, or left ventricular [LV] assist device) was determined.
      Predictors of outcome, particularly race, parameters of LV dysfunction (LVEF),
      and remodeling (left ventricular end-diastolic diameter [LVEDD]) at presentation,
      were assessed by univariate and multivariate analyses. RESULTS: The cohort was
      30% black, 65% white, 5% other; the mean patient age was 30 +/- 6 years; and 88%
      were receiving beta-blockers and 81% angiotensin-converting enzyme inhibitors or
      angiotensin receptor blockers. The LVEF at study entry was 0.35 +/- 0.10, 0.51 +/
      0.11 at 6 months, and 0.53 +/- 0.10 at 12 months. By 1 year, 13% had experienced
      major events or had persistent severe cardiomyopathy with an LVEF <0.35, and 72%
      achieved an LVEF >=0.50. An initial LVEF <0.30 (p = 0.001), an LVEDD >=6.0 cm (p
      < 0.001), black race (p = 0.001), and presentation after 6 weeks post-partum (p =
      0.02) were associated with a lower LVEF at 12 months. No subjects with both a
      baseline LVEF <0.30 and an LVEDD >=6.0 cm recovered by 1 year post-partum,
      whereas 91% with both a baseline LVEF >=0.30 and an LVEDD <6.0 cm recovered (p <
      0.00001). CONCLUSIONS: In a prospective cohort with PPCM, most women recovered;
      however, 13% had major events or persistent severe cardiomyopathy. Black women
      had more LV dysfunction at presentation and at 6 and 12 months post-partum.
      Severe LV dysfunction and greater remodeling at study entry were associated with
      less recovery. (Investigations of Pregnancy Associated Cardiomyopathy [IPAC];
      NCT01085955).

PMID- 26293762
TI  - Temporal Trends and Factors Associated With Cardiac Rehabilitation Referral Among
      Patients Hospitalized With Heart Failure: Findings From Get With The Guidelines
      Heart Failure Registry.
AB  - BACKGROUND: Current guidelines recommend cardiac rehabilitation (CR) in medically
      stable outpatients with heart failure (HF); however, temporal trends and factors
      associated with CR referral among these patients in real-world practice are not
      entirely known. OBJECTIVES: The purpose of this study was to assess proportional
      use, temporal trends, and factors associated with CR referral at discharge among
      patients admitted with decompensated HF. METHODS: Using data from a national Get
      With the Guidelines-Heart Failure registry, we assessed the temporal trends in CR
      referral among eligible patients with HF with reduced ejection fraction (HFrEF)
      and HF with preserved ejection fraction (HFpEF) at discharge after HF
      hospitalization between 2005 and 2014. On multivariable analysis, we also
      assessed patient- and hospital-level characteristics that are associated with CR
      referral. RESULTS: Among 105,619 HF patients (48% with HFrEF, 52% with HFpEF),
      10.4% (12.2% with HFrEF, 8.8% with HFpEF) received CR referral at discharge. A
      significant increase in CR referral rates was observed among both HFpEF and HFrEF
      patients over the study period (ptrend <0.0001 for HFrEF, HFpEF, and overall).
      Compared with patients discharged without CR referral, patients referred for CR
      were younger, predominantly men, and more likely to receive evidence-based HF
      therapies at discharge. On multivariable analysis, younger age, fewer comorbid
      conditions, and in-hospital procedures such as coronary artery bypass grafting,
      percutaneous coronary intervention, and cardiac valve surgery were most strongly
      associated with CR referral. CONCLUSIONS: Only one-tenth of eligible HF patients
      received CR referral at discharge after hospitalization for HF. The proportional
      use of CR referral is increasing over time among both HFrEF and HFpEF patients.
      Further strategies to improve physician and patient awareness in regard to the
      benefit of CR should be used to increase CR referral among patients with HF.

PMID- 26293763
TI  - Temporal Trends and Factors Associated With Cardiac Rehabilitation Referral Among
      Patients Hospitalized With Heart Failure: Awaiting the Uptick.

PMID- 26293765
TI  - Cord Blood Samples: A Less Explored Tool in Early Diagnosis of Neonatal
      Cardiovascular Disease.

PMID- 26293764
TI  - Serum Biomarkers of Inflammation, Fibrosis, and Cardiac Function in Facilitating
      Diagnosis, Prognosis, and Treatment of Anti-SSA/Ro-Associated Cardiac Neonatal
      Lupus.
AB  - BACKGROUND: Cardiac manifestations of neonatal lupus (cardiac NL) include
      congenital heart block and cardiomyopathy. Several candidate biomarkers were
      evaluated in cases at risk for cardiac NL on the basis of potential roles in
      inflammation, fibrosis, and cardiac dysfunction: C-reactive protein (CRP); NT-pro
      B-type natriuretic peptide (NT-proBNP); troponin I; matrix metalloproteinase
      (MMP)-2; urokinase plasminogen activator (uPA); urokinase plasminogen activator
      receptor (uPAR); plasminogen; and vitamin D. OBJECTIVES: Identification of
      maternal and fetal biomarkers associated with development and morbidity of
      cardiac NL should provide clues to pathogenesis with translational implications
      for management. METHODS: Cord (139) and maternal (135) blood samples collected
      during pregnancies at risk for cardiac NL were available for study. Levels of
      cord and maternal CRP, cord NT-proBNP, and cord troponin I were evaluated using
      multiplex assays. Cord and maternal vitamin D were assessed by liquid
      chromatography-mass spectrometry. MMP-2, uPA, uPAR, and plasminogen were
      evaluated using ELISA. RESULTS: Cord CRP, NT-proBNP, MMP-2, uPA, uPAR, and
      plasminogen levels were higher in cardiac NL-affected fetuses than in unaffected
      cases, independent of maternal rheumatic disease, season at highest risk of
      cardiac NL development, and medications taken during pregnancy. These biomarkers
      were positively associated with a disease severity score derived from known risk
      factors for mortality in cardiac NL. Maternal CRP and cord troponin I levels did
      not differ between the groups. Cord and maternal vitamin D levels were not
      significantly associated with cardiac NL, but average maternal vitamin D level
      during pregnancy was positively associated with longer time to postnatal
      pacemaker placement. CONCLUSIONS: These data support the association of fetal
      reactive inflammatory and fibrotic components with development and morbidity of
      cardiac NL. Following CRP and NT-proBNP levels after birth can potentially
      monitor severity and progression of cardiac NL. MMP-2 and the
      uPA/uPAR/plasminogen cascade provide therapeutic targets to decrease fibrosis.
      Although decreased vitamin D did not confer increased risk, given the positive
      influence on postnatal outcomes, maternal levels should be optimized.

PMID- 26293766
TI  - Cardiac Fibrosis in Patients With Atrial Fibrillation: Mechanisms and Clinical
      Implications.
AB  - Atrial fibrillation (AF) is associated with structural, electrical, and
      contractile remodeling of the atria. Development and progression of atrial
      fibrosis is the hallmark of structural remodeling in AF and is considered the
      substrate for AF perpetuation. In contrast, experimental and clinical data on the
      effect of ventricular fibrotic processes in the pathogenesis of AF and its
      complications are controversial. Ventricular fibrosis seems to contribute to
      abnormalities in cardiac relaxation and contractility and to the development of
      heart failure, a common finding in AF. Given that AF and heart failure frequently
      coexist and that both conditions affect patient prognosis, a better understanding
      of the mutual effect of fibrosis in AF and heart failure is of particular
      interest. In this review paper, we provide an overview of the general mechanisms
      of cardiac fibrosis in AF, differences between fibrotic processes in atria and
      ventricles, and the clinical and prognostic significance of cardiac fibrosis in
      AF. 

PMID- 26293767
TI  - Time to Change Our Focus: Defining, Promoting, and Impacting Cardiovascular
      Population Health.
AB  - Despite numerous groundbreaking advances in the field, cardiovascular disease
      remains the leading cause of mortality in the United States, accounting for more
      than 787,000 deaths per year. Already leading the world in per capita healthcare
      expenditure, U.S. medical costs related to cardiovascular disease are projected
      to triple by 2030, to over $800 billion annually. The medical community's
      traditional disproportionate focus on treating cardiovascular disease, relative
      to promoting cardiovascular health, is an important contributor to these
      expenses. To ensure continued reductions in the burden of cardiovascular disease,
      as well as the overall sustainability of the healthcare system, a paradigm shift
      that places more emphasis on cardiovascular health promotion throughout the life
      course is required. This review will discuss the current definitions of
      cardiovascular health, as well as strategies for promoting and impacting
      cardiovascular health at both the local and national level. 

PMID- 26293768
TI  - Picking a Fellowship: Getting Your Priorities Straight in a Timely Fashion.

PMID- 26293769
TI  - Exercise Cardiac Output Limitation in Pectus Excavatum.

PMID- 26293770
TI  - Vagal Modulation of Atrial Fibrillation.

PMID- 26293771
TI  - Reply: Vagal Modulation of Atrial Fibrillation.

PMID- 26293772
TI  - Less Dyspnea Is Better Than More Dyspnea: More or Less?

PMID- 26293773
TI  - 1-Year Results From the NOTION Randomized Clinical Trial: No News Is Good News?

PMID- 26293774
TI  - Reply: 1-Year Results From the NOTION Randomized Clinical Trial: Weighing
      Complications Against Functional Outcomes.

PMID- 26293775
TI  - Identification and characterization of microRNAs expressed in human breast cancer
      chemo-resistant MCF-7/Adr cells by Solexa deep-sequencing technology.
AB  - BACKGROUND/AIM: Breast cancer is the most common type of tumor in female and
      chemoresistance has been a major clinical obstacle to the treatment in clinical
      patients. miRNA was one of the factors demonstrated to play certain roles in
      chemoesistance in breast cancer. In this study, we exploited Solexa deep
      sequencing technology to identify differentially expressed miRNA from samples in
      vitro, trying to find novel relationship between miRNA and chemoresistance in
      breast cancer. METHODS: The human breast cancer MCF-7 cell line was pulse
      selected with doxorubicin (10 pulses, once a week for 4h, with 1MUM doxorubicin)
      to generate MCF-7/Adr cells. Total RNA was extracted from the treated and
      untreated MCF-7 cells and subsequently subjected to real time PCR. Two small RNA
      libraries of MCF7NON and MCF7ADR were established to record the Solexa sequencing
      results of the PCR products above. All the sequencing results were verified by
      Stem-loop real-time PCR. GO annotation and KEGG analysis program were exploited
      to enrich the differentially expressed miRNAs. RESULTS: The results showed that
      214,822 and 378,597 reads were mapped in the MCF7ADR and MCF7NON libraries when
      aligned to hairpin structure respectively. Meanwhile, 1323 and 520 reads were
      mapped when aligned to mature sequences. In addition, 310 known mature miRNAs
      were coexpressed in both libraries. Comparing the MCF7ADR group to the MCF7NON
      group, 18 miRNAs were significantly differentially expressed. GO annotation and
      KEGG analysis showed that the target genes were enriched in regulation of
      transcription and development as well as Wnt signaling pathway, MAPK signaling
      pathway and TGF-beta signaling pathway. CONCLUSION: The results proved that the
      Solexa deep sequencing was a powerful and reliable platform to analyze small
      RNAs. And further investigation should be conducted for the biological process
      and pathways that have been identified and more efforts should be made to
      research the mechanism of chemoresistance in breast cancer.

PMID- 26293777
TI  - Chimpanzee lip-smacking facilitates cooperative behaviour.
AB  - Signalling plays an important role in facilitating and maintaining affiliative or
      cooperative interactions in social animals. Social grooming in primates is an
      example of an interaction that requires coordination between partners but little
      is known about communicative behaviours facilitating this activity. In this
      study, we analysed the communication of wild chimpanzees of Budongo Forest,
      Uganda, as they entered and maintained a naturally occurring cooperative
      interaction: social grooming. We found that lip-smacking, a distinct multimodal
      oral gesture produced during grooming, coordinated this activity. Lip-smacking at
      the beginning of grooming bouts was significantly more often followed by longer
      and reciprocated bouts than silent grooming initiations. Lip-smacks were more
      likely to be produced when the risk of termination of the interaction by the
      recipient was high, for instance when grooming vulnerable body parts. Groomers
      were also more likely to produce lip-smacks during face-to-face grooming where
      the visual aspect of the signal could be perceived. Data are consistent with the
      hypothesis that chimpanzee lip-smacks function to coordinate and prolong social
      grooming, suggesting that this oral signal is an example of a communicative
      behaviour facilitating cooperative behaviour in chimpanzees. 

PMID- 26293779
TI  - Argentines' collective memories of the military Junta of 1976: differences and
      similarities across generations and ideology.
AB  - Although memories about a nation's past usually are semantic in nature, a
      distinction needs to be made between lived and distant semantic collective
      memories. The former refers to memories of community-relevant events occurring
      during the lifetime of the rememberer, whereas the latter to memories of distant
      events. Does the content of lived and distant semantic collective memories
      differ? Employing both free and cued recall, we examined the memories of younger
      and older Argentines of the Military Junta of 1976. We also examined the effects
      of political ideology. Content analysis indicated that (1) lived semantic
      collective memories were more likely to contain personal recollections than
      distant semantic collective memories, even though those with distant semantic
      collective memories could have incorporated memories of the parent's personal
      experience in their recollections, (2) lived semantic collective memories
      contained more causal statements, and (3) those on the Right with distant
      semantic collective memories were more likely to claim that they "Don't know" or
      offer positive accounts of the Junta, suggesting a need to "defend" the
      reputation of those on the Right. The results are discussed in terms of the goals
      and plans different generations might have when recollecting their nation's past.

PMID- 26293778
TI  - A clinicopathological study of episomal papillomavirus infection of the human
      placenta and pregnancy complications.
AB  - Viral infections are known to adversely affect pregnancy, but scant attention has
      been given to human papilloma virus (HPV) infection. We aimed to determine the
      molecular and histopathological features of placental HPV infection, in
      association with pregnancy complications including fetal growth restriction, pre
      maturity, pre-eclampsia, and diabetes. Three hundred and thirty-nine placentae
      were selected based on the presence or absence of pregnancy complications. Five
      independent methods were used to identify HPV in the placenta, namely,
      immunohistochemistry for L1 viral capsid, in situ hybridization to high-risk HPV
      DNA, PCR, western blotting, and transmission electron microscopy. Pregnancy
      complications and uterine cervical smear screening results were correlated with
      placental HPV histopathology. In this study, which was deliberately biased
      towards complications, HPV was found in the decidua of 75% of placentae (253/339)
      and was statistically associated with histological acute chorioamnionitis
      (P<0.05). In 14% (35/253) of the HPV positive cases, HPV L1 immunoreactivity also
      occurred in the villous trophoblast where it was associated with a
      lymphohistiocytic villitis (HPV-LHV), and was exclusively of high-risk HPV type.
      HPV-LHV significantly associated with fetal growth restriction, preterm delivery,
      and pre-eclampsia (all P<0.05). All cases of pre-eclampsia (20/20) in our cohort
      had high-risk placental HPV. A further 55 cases (22%, 55/253) of HPV positive
      placentae had minimal villous trophoblast HPV L1 immunoreactivity, but a
      sclerosing pauci-immune villitis, statistically associated with diabetes (49.1%,
      27/55, P<0.05). For women with placental HPV, 33% (69/207) had an HPV-related
      positive smear result before pregnancy compared with (9.4% 8/85) of women with
      HPV-negative placentae (P=0.0001). Our findings support further investigations to
      determine if vaccination of women and men will improve pregnancy outcomes. 

PMID- 26293780
TI  - Helical rearrangement of photoactivated rhodopsin in monomeric and dimeric forms
      probed by high-angle X-ray scattering.
AB  - Light-induced helical rearrangement of vertebrate visual rhodopsin was directly
      monitored by high-angle X-ray scattering (HAXS), ranging from Q (= 4pi sin
      theta/lambda) = 0.03 A(-1) to Q = 1.5 A(-1). HAXS of nanodiscs containing a
      single rhodopsin molecule was performed before and after photoactivation of
      rhodopsin. The intensity difference curve obtained by HAXS agreed with that
      calculated from the crystal structure of dark state rhodopsin and metarhodopsin
      II, indicating that the conformational change of monomeric rhodopsin in the
      membrane is consistent with that occurring in the crystal. On the other hand, the
      HAXS intensity difference curve of nanodiscs containing two rhodopsin molecules
      was significantly reduced, similar to that calculated from the crystal structure
      of the deprotonated intermediate, without a large conformational change. These
      results suggest that rhodopsin is dimerized in the membrane and that the
      interaction between rhodopsin molecules modulates structural changes. 

PMID- 26293781
TI  - Cutaneous anthrax: evaluation of 28 cases in the Eastern Anatolian region of
      Turkey.
AB  - CONTEXT: Anthrax is an endemic disease in developing countries. Human cases are
      usually associated with animal products. About 95% of naturally acquired cases
      are cutaneous anthrax. OBJECTIVE: In this study, cutaneous anthrax cases from the
      Elazig province (the Eastern Anatolian region) of Turkey seen in our hospital
      within a 6-year period were evaluated with respect to epidemiological and
      clinical features, diagnosis, treatment and outcome. METHODS: Twenty-eight
      patients with cutaneous anthrax observed between January 2009 and December 2014
      were investigated retrospectively. The diagnosis of cutaneous anthrax was based
      on detailed history, dermatologic findings, including painless, ulcers covered by
      a characteristic black eschar and/or microbiological procedures, including Gram
      stain and culture of materials obtained from the lesions. RESULTS: Of the 28
      patients followed up with cutaneous anthrax diagnosis, 14 (50%) were female and
      14 (50%) were male. The mean age of the cases was 39.6 years (age range 17-65
      years). The patients have an incubation period in the range of 1-9 days (mean 4.6
      +/- 0.5 days). The cases were seen between April and November of each year during
      the study period. Twenty-three cases (82%) had a history of contact with animals
      or animal products. Twenty patients (71.4%) showed malignant pustules and eight
      (28.6%) malignant edema. Bacillus anthracis was isolated in three cases (10.7%)
      and Gram stain smear were positive in five cases (17.8%). All patients were
      treated successfully with penicillin or ciprofloxacin. Systemic corticosteroids
      were added to the antibiotic treatment in six patients with malignant edema.
      Sepsis no developed in patients, all the cases recovered. CONCLUSION: Anthrax is
      still a serious public health problem in Turkey. Cutaneous anthrax must always be
      kept in mind when characteristic lesions such as a painless ulcer with vesicles,
      edema, and a history of contact with animals or animal products are observed in
      an individual. Early and correct diagnosis significantly affects course of the
      disease. Protective precautions such as vaccination of animals against anthrax
      and education of the population would reduce the incidence of the disease.

PMID- 26293783
TI  - Seizing control of epileptic activity can improve outcome.
AB  - In epileptic encephalopathy, the seizures and interictal epileptiform activity
      create additional neurocognitive dysfunction beyond that due to the underlying
      etiology. Treatment leading to a reduction in seizures or interictal
      abnormalities may help improve neurocognitive function in these situations. The
      focus of our discussion is reviewing data that support the concept that treatment
      can impact outcome independent of the etiology in some cases. 

PMID- 26293782
TI  - EGCG induces G-CSF expression and neutrophilia in experimental sepsis.
AB  - A major green tea component, epigallocatechin-3-gallate (EGCG), has been proven
      protective against lethal sepsis in experimental setting, but its protective
      mechanisms remain incompletely understood. Here, we provide evidence to support
      EGCG's capacities in stimulating G-CSF production and neutrophilia in vivo. In an
      animal model of sepsis, EGCG significantly elevated peritoneal levels of G-CSF
      and several chemokines (e.g., MCP-1/CCL2 and MIP-1gamma/CCL9), and consequently
      increased peritoneal neutrophil numbers (neutrophilia) at a late stage. In vitro,
      EGCG divergently affected HMGB1-mediated production of several chemokines:
      reducing CXCL15 and RANTES/CCL5, but elevating G-CSF and MIP-1alpha/CCL3
      production by peritoneal macrophages. Similarly, it significantly induced the
      expression and secretion of G-CSF and MIP-1alpha/CCL3 in human peripheral blood
      mononuclear cells. Based on our preliminary data, it may be important to search
      for anti-inflammatory and G-CSF-stimulating agents for the clinical management of
      inflammatory diseases. 

PMID- 26293785
TI  - Physical health of singleton children born after frozen embryo transfer using
      slow freezing: a 3-year follow-up study.
AB  - STUDY QUESTION: Are there differences in the physical health of singleton
      children born after frozen embryo transfer (FET) compared with children born
      after fresh embryo transfer (fresh ET)? SUMMARY ANSWER: Register-based health
      indicators were similar among FET and fresh ET singletons during a 3-year follow
      up. WHAT IS KNOWN ALREADY: Large cohort studies have shown that perinatal
      outcomes are similar or even better in FET than fresh ET children. The early
      childhood morbidity among FET and fresh ET children has been shown to be quite
      similar, but so far these studies have been small. The short-term health outcomes
      of assisted reproductive technology (ART) children have been shown to be slightly
      worse compared with spontaneously conceived children. STUDY DESIGN, SIZE,
      DURATION: This register-based study includes women who had undergone ART
      treatments leading to singleton live births (n = 4758 children) in 1995-2006. A
      10% random sample of women with spontaneous pregnancies from the Finnish Medical
      Birth Register (FMBR) served as the reference group (n = 31 137 children). The
      children were identified through the FMBR by using the mother's personal
      identification (ID) number. Children's ID numbers were linked with two nationwide
      registries; the Finnish Hospital Discharge Register and the Cause-of-Death
      Register at Statistics Finland. Information on all visits was received until 2009
      using ICD-10 codes. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study includes
      1825 children born after FET, 2933 children born after fresh ET and 31 137
      children born after spontaneous pregnancies. The risk estimates for diseases were
      adjusted for the child's year of birth and maternal age, parity, socio-economic
      status and prematurity. The study focused on the differences between FET and
      fresh ET children. MAIN RESULTS AND THE ROLE OF CHANCE: Most health indicators
      were similar among FET and fresh ET children during the 3-year follow-up. The
      most common discharge diagnoses, including gastroenteritis and colitis, otitis,
      upper and lower respiratory diseases, asthma and allergies were similar between
      the ART groups. A large proportion of FET children (70.1%) and fresh ET children
      (69.9%) had visited a hospital at least once (P = 0.877). The risk of hospital
      admission did not differ between the two groups after adjusting for premature
      births [adjusted odds ratio (aOR) 1.01; 0.88-1.17]. Comparing with children born
      after spontaneously conceived pregnancies, the risk of hospital admission was
      slightly increased in the ART group, even after adjusting for premature births
      (aOR 1.10; 1.02-1.19). LIMITATIONS, REASONS FOR CAUTION: Due to the study design,
      we were not able to control for some parental background factors, such as the
      cause and length of infertility. Furthermore, the health registries do not
      include data on the growth of the children. Our findings are generalizable only
      to the slow-freezing method. WIDER IMPLICATIONS OF THE FINDINGS: Our study
      provides further evidence of the safety of embryo cryopreservation. The early
      physical health of FET children is similar to that of children born after fresh
      ET. STUDY FUNDING/COMPETING INTERESTS: This study was funded by the University
      Hospital of Oulu and Helsinki, Finland. The National Institute for Health and
      Welfare (THL) covered the data linkages and the work of Mika Gissler. There are
      no competing interests to be reported.

PMID- 26293784
TI  - Polymorphic variation of hypoxia inducible factor-1 A (HIF1A) gene might
      contribute to the development of knee osteoarthritis: a pilot study.
AB  - BACKGROUND: Osteoarthritis (OA) is a multifactorial degenerative condition of the
      whole joint with a complex pathogenesis whose development and progression is
      significantly mediated by interactions between the joint cartilage and articular
      tissues, particularly, proinflammatory mediators and oxidative stress, which
      results in cartilage deterioration and subchondral bone destruction. HIF-1 alpha
      regulates oxygen homeostasis in hypoxic tissues such as joint cartilage;
      efficiency of transcriptional activity of the HIF1A gene is strongly influenced
      by the presence of polymorphic variants. Given the loss of articular cartilage
      and with intention to restore damaged tissue, WISP-1 participates in the
      development of subchondral bone; further, its expression is highly increased in
      chondrocytes of OA patients. The aim of this study was to evaluate gene
      frequencies of HIF1A and WISP1 polymorphisms in Mexican patients suffering from
      knee OA. METHODS: We determined HIF1A rs11549465 (P582S), rs11549467 (A588T), and
      rs2057482 (C191T), and WISP1 rs2929970 (A2364G) polymorphisms in 70 Mexican
      patients with knee OA and compare them to those present in 66 ethnically matched
      healthy controls. Genotyping for these polymorphisms was performed by Real-Time
      PCR using TaqMan probes. RESULTS: Gene frequencies exhibited a significant
      increase of the CC genotype of rs11549465 polymorphism in knee OA patients as
      compared with those present in controls (P = 0.003 OR = 5.7, 95% CI = 1.7-21.6);
      CT genotype and T allele showed decreased frequency in the knee OA group vs. the
      controls (P = 0.003 OR = 0.2, CI = 0.05-0.6; and P = 0.004 OR = 0.2, CI = 0.05
      0.65, respectively). Allele frequencies of the other polymorphic variants were
      similar in both patients and controls. CONCLUSIONS: These results suggest that
      the presence of the rs11549465 SNP (HIF1A) plays a role protective in the loss of
      articular cartilage in our population, and offers the possibility to further
      study the molecular mechanisms within cartilage and subchondral bone.

PMID- 26293786
TI  - Detection of Acanthamoeba on the ocular surface in a Spanish population using the
      Schirmer strip test: pathogenic potential, molecular classification and
      evaluation of the sensitivity to chlorhexidine and voriconazole of the isolated
      Acanthamoeba strains.
AB  - Pathogenic strains of Acanthamoeba are causative agents of a sight-threatening
      infection of the cornea known as Acanthamoeba keratitis, which is often
      associated with the misuse of contact lenses. However, there is still a question
      remaining to be answered, which is whether these micro-organisms are present on
      the ocular surface of healthy individuals. Therefore, the aim of this study was
      to determine the presence of Acanthamoeba on the ocular surface in healthy
      patients and also in those with other ocular surface infections. Sterile Schirmer
      test strips were used to collect samples from a group of patients who attended an
      ophthalmology consultation at the Hospital del Norte, Icod de los Vinos,
      Tenerife, Canary Islands. Most of the patients (46 individuals, 79.31  %)
      presented ocular surface pathologies such as blepharitis or conjunctivitis; the
      rest did not present any pathology. None of the patients included in the study
      wore contact lenses. The collected samples were cultured in 2  % non-nutrient
      agar plates and positive plates were then cultured in axenic conditions for
      further analyses. Molecular analysis classified all isolated strains as belonging
      to Acanthamoeba genotype tbl4, and osmotolerance and thermotolerance assays
      revealed that all strains were potentially pathogenic. Furthermore, all strains
      were assayed for sensitivity against voriconazole and chlorhexidine. Assays
      showed that both drugs were active against the tested strains. In conclusion, the
      Schirmer strip test is proposed as an effective tool for the detection of
      Acanthamoeba on the ocular surface. 

PMID- 26293788
TI  - Dental materials used for metal-free restorations: Recent advances and future
      challenges.

PMID- 26293787
TI  - Discovery and mapping of genomic regions governing economically important traits
      of Basmati rice.
AB  - BACKGROUND: Basmati rice, originated in the foothills of Himalayas, commands a
      premium price in the domestic and international markets on account of its unique
      quality traits. The complex genetic nature of unique traits of Basmati as well as
      tedious screening methodologies involved in quality testing have been serious
      constraints to breeding quality Basmati. In the present study, we made an attempt
      to identify the genomic regions governing unique traits of Basmati rice. RESULTS:
      A total of 34 Quantitative Trait Loci (QTLs) for 16 economically important traits
      of Basmati rice were identified employing F(2), F(3) and Recombinant Inbred Line
      (RIL) mapping populations derived from a cross between Basmati370 (traditional
      Basmati) and Jaya (semi-dwarf rice). Out of which, 12 QTLs contributing to more
      than 15 % phenotypic variance were identified and considered as major effect
      QTLs. Four major effect QTLs coincide with the already known genes viz., sd1,
      GS3, alk1 and fgr governing plant height, grain size, alkali spreading value and
      aroma, respectively. For the remaining major QTLs, candidate genes were predicted
      as auxin response factor for filled grains, soluble starch synthase 3 for
      chalkiness and VQ domain containing protein for grain breadth and grain weight
      QTLs, based on the presence of non-synonymous single nucleotide polymorphism
      (SNPs) that were identified by comparing Basmati genome sequence with that of
      Nipponbare. CONCLUSIONS: To the best of our knowledge, the current study is the
      first attempt ever made to carry out genome-wide mapping for the dissection of
      the genetic basis of economically important traits of Basmati rice. The promising
      QTLs controlling important traits in Basmati rice, identified in this study, can
      be used as candidates for future marker-assisted breeding.

PMID- 26293789
TI  - Localized peritonitis from perforated sigmoid diverticulum in a non-reducible
      inguinal hernia. Case report.

PMID- 26293790
TI  - Structured hands-on workshop decreases the over-detection rate of obstetrical
      anal sphincter injuries.
AB  - PURPOSE: The purpose of this study was to assess the effect of a structured hands
      on workshop on the detection rate of obstetric anal sphincter injuries. METHODS:
      All physicians attending the delivery ward in our institution participated in a
      structured obstetric anal sphincter injury hands-on workshop developed by Dr.
      Ranee Thakar and Dr. Abdul Sultan which demonstrated proper identification and
      techniques for obstetric anal sphincter injury detection and repair. We
      retrospectively reviewed the electronic records of all singleton-pregnancy women
      who delivered vaginally (vertex presentation) during the 2 years prior to and 1
      year following the workshop to assess the workshop's effect on the rate of
      detection of obstetric anal sphincter injuries. RESULTS: Overall, 20,484 women
      met the inclusion criteria during the study period and were eligible for final
      analysis. There were no significant differences in patient's characteristics
      between the groups. Women in the pre-workshop group had a higher rate of
      obstetric anal sphincter injuries than the post-workshop group (0.4 vs. 0.2 %, p
      = 0.005). On multivariate analysis, factors independently associated with a
      decreased risk for obstetric anal sphincter injuries were deliveries in the post
      workshop period (odds ratio 0.43, 95 % confidence interval 0.24-0.79, p = 0.006),
      parity (odds ratio 0.37, 95 % confidence interval 0.25-0.54, p < 0.001), and
      spontaneous vaginal delivery (odds ratio 0.43, 95 % confidence interval 0.26
      0.71, p = 0.001). CONCLUSIONS: A proper detection of obstetric anal sphincter
      injuries may depend on the experience of the assessor. A structured hands-on
      workshop is important to avoid over diagnosis third-degree perineal tears.

PMID- 26293791
TI  - Long-term surveillance of locally advanced rectal cancer patients with
      neoadjuvant chemoradiation and aggressive surgical treatment of recurrent
      disease: a consecutive single-centre experience.
AB  - PURPOSE: The aim of this study was to analyse the long-term outcome of rectal
      cancer patients who submitted to preoperative chemoradiation with consecutive
      intensive follow-up and aggressive surgical treatment of recurrent disease.
      METHODS: Patients with locally advanced (cT3-4 Nx M0-1) mid/low rectal cancer
      were treated at a tertiary university hospital with preoperative long-course
      chemoradiation followed by resection (according to a prospective study protocol).
      After resection, all patients were urged to participate in a standardised, risk
      independent intensive follow-up program. All curatively treated patients (n =
      153, 96 %) were included in our long-term analysis with respect to curative re
      resection of recurrent disease. RESULTS: Of 153 patients, 143 (93 %) participated
      in our follow-up program: 63 % were surveyed longer than 5 years after primary
      therapy (mean follow-up 75 months, 95 % CI 67.8-82.2). Fifty-five (36 %) patients
      developed cancer recurrence (mean 27.8 months, 95 % CI 20.6-34.9, range 3-108),
      giving a disease-free survival rate of 68.5 and 60.7 % at 5 and 10 years; 21 (38
      %) patients were re-resected curatively and 58 (38 %) patients died during the
      observation period, giving an overall survival rate of 70.8 and 57.5 % at 5 and
      10 years. Multivariate analysis found tumour differentiation (P < 0.01),
      operative procedure (P < 0.05) and downstaging (P < 0.01) to be independent
      variables influencing overall survival. CONCLUSIONS: The combination of
      multimodal therapy and aggressive surgical treatment of metastases including
      repeated re-resections in curative intention is relevant in order to chronify the
      disease. Thus, both intensive and extended follow-up beyond 5 years appear to be
      mandatory.

PMID- 26293793
TI  - Comparative studies of the immunogenicity and protective potential of biofilm vs
      planktonic Staphylococcus aureus vaccine against bovine mastitis using non
      invasive mouse mastitis as a model system.
AB  - This study was undertaken to compare the immunogenicity and protective potential
      of biofilm vs planktonic Staphylococcus aureus vaccine for the prevention of
      mastitis using the mouse as a model system. Mice immunized with formalin-killed
      whole cell vaccine of S. aureus residing in a biofilm when delivered via an
      intramammary route produced a cell mediated immune response. Mice immunized with
      this biofilm vaccine showed significant reductions in colonization by S. aureus
      in mammary glands, severity of clinical symptoms and tissue damage in mammary
      glands in comparison with the mice immunized with formalin-killed whole cells of
      planktonic S. aureus. The planktonic vaccine administered by a subcutaneous route
      produced a significantly higher humoral immune response (IgG1 and IgG) than the
      biofilm vaccine. However, considering the host response, tissue damage, the
      clinical severity and colonization of S. aureus in mammary glands, the biofilm
      vaccine performed better in immunogenicity and protective potential when
      administered by the intramammary route. 

PMID- 26293792
TI  - Poly(D, L-lactide-co-glycolide) nanoparticles as delivery agents for photodynamic
      therapy: enhancing singlet oxygen release and photototoxicity by surface PEG
      coating.
AB  - Poly(D, L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) are being considered
      as nanodelivery systems for photodynamic therapy. The physico-chemical and
      biological aspects of their use remain largely unknown. Herein we report the
      results of a study of PLGA NPs for the delivery of the model hydrophobic
      photosensitizer ZnTPP to HeLa cells. ZnTPP was encapsulated in PLGA with high
      efficiency and the NPs showed negative zeta potentials and diameters close to 110
      nm. Poly(ethylene glycol) (PEG) coating, introduced to prevent opsonization and
      clearance by macrophages, decreased the size and zeta potential of the NPs by
      roughly a factor of two and improved their stability in the presence of serum
      proteins. Photophysical studies revealed two and three populations of ZnTPP and
      singlet oxygen in uncoated and PEGylated NPs, respectively. Singlet oxygen is
      confined within the NPs in bare PLGA while it is more easily released into the
      external medium after PEG coating, which contributes to a higher
      photocytotoxicity towards HeLa cells in vitro. PLGA NPs are internalized by
      endocytosis, deliver their cargo to lysosomes and induce cell death by apoptosis
      upon exposure to light. In conclusion, PLGA NPs coated with PEG show high
      potential as delivery systems for photodynamic applications. 

PMID- 26293794
TI  - Laparoscopic pyloroplasty is a safe and effective first-line surgical therapy for
      refractory gastroparesis.
AB  - INTRODUCTION: Surgical options for symptomatic delayed gastric emptying include
      gastric stimulator implantation, subtotal gastrectomy, and pyloroplasty.
      Pyloroplasty has been shown to improve gastric emptying yet is seldom described
      as a primary treatment for gastroparesis. We present a single-institution
      experience of laparoscopic Heineke-Mikulicz pyloroplasty (LP) as treatment for
      gastroparesis. METHODS AND PROCEDURES: A prospective foregut surgery database was
      queried for LP over a 5-year period. Charts were reviewed for indications,
      complications, symptom score, and outcomes. Gastroparesis was defined by (1)
      abnormal gastric emptying study, (2) endoscopic visualization of retained food
      after prolonged NPO status, or (3) clinical symptoms suspicious of vagal nerve
      injury following complex re-operative foregut surgery. Results were analyzed
      using a paired T test and single-factor ANOVA. RESULTS: One hundred and seventy
      seven LP patients were identified and reviewed. One hundred and five had a
      concurrent fundoplication for objective reflux. There were no intraoperative
      complications or conversions to laparotomy. Overall morbidity rate was 6.8% with
      four return to OR and two confirmed leaks (1.1% leak rate). Average length of
      stay was 3.5 days, and readmission rate was 7%. Eighty-six percent had
      improvement in GES with normalization in 77%. Gastric emptying half-time
      decreased from 175 +/- 94 to 91 +/- 45 min. Nineteen patients (10.7%) had
      subsequent surgical interventions: gastric stimulator implantation (12), feeding
      jejunostomy and/or gastrostomy tube (6), or subtotal gastrectomy (4). Symptom
      severity scores for nausea, vomiting, bloating, abdominal pain, and early satiety
      decreased significantly at 3 months. CONCLUSION: Laparoscopic pyloroplasty
      improves or normalizes gastric emptying in nearly 90% of gastroparesis patients
      with very low morbidity. It significantly improves symptoms of nausea, vomiting,
      bloating, and abdominal pain. Some patients may go on to another surgical
      treatment for GP, but it remains a safe and less invasive alternative to a
      subtotal gastrectomy in these clinically challenging patients.

PMID- 26293795
TI  - The first clinical use of domestically produced Chinese minimally invasive
      surgical robot system "Micro Hand S".
AB  - BACKGROUND: Robot-assisted minimally invasive surgery (MIS) has shown tremendous
      advances over the traditional technique. However, current commercialized systems
      are complicated and huge, which vastly raises system cost and requirements for
      operation room. Central South University in collaboration with Tianjin University
      developed one domestically produced Chinese minimally invasive surgical (MIS)
      robot system "Micro Hand S" in 2013. Recently, our center launched the first
      clinical trials of the robot, including one case of robotic gastric perforation
      repair and two cases of robotic appendectomy. METHODS: In march 2014, one patient
      with gastric perforation and two patients with acute appendicitis who underwent
      robotic perforation repair and robotic appendectomy respectively. In these
      procedures, we firstly use "Micro Hand S" robot system. All of the patients were
      followed for 3 months, Total robotic operation time, Intra-operative blood loss
      and pre- and postoperative changes in routine blood test, liver function test,
      renal function test and major complications were recorded. RESULTS: "Micro Hand
      S" succeeded in accomplishing operations. No intraoperative complications or
      technical problems were encountered. At a three-month follow-up, patients were
      found to be progressing well, without evidence of adverse reactions. CONCLUSIONS:
      The domestic surgical robot system which was verified as safe and effective
      through these trials. The proposed design method is an effective way to solve
      some of drawbacks that exist in the former generations of the da Vinci surgical
      system.

PMID- 26293796
TI  - Comparative analysis of pathologic processes developing in mice housed in SPF vs
      non-SPF conditions and treated with cyclophosphamide and dsDNA preparation.
AB  - In our earlier studies, we observed that when mice are treated with
      cyclophosphamide and fragmented exogenous dsDNA (18-30 h post cytostatic
      treatment), they develop a very characteristic set of symptoms and 80-90% of such
      animals succumb within 6-25 days. This was called "delayed death" phenomenon, and
      the gap between cyclophosphamide and DNA injections required for such phenotype
      to develop was termed "death window". We established that mice succumbed to multi
      organ failure, which was caused by systemic inflammation and sepsis. These
      processes unfolded along with accidental involution of lymphoid organs, which
      resulted from the failure of CD34(+) hematopoietic stem cells to differentiate
      into lymphoid lineage progenitors. Here we compare SPF and non-SPF animals, and
      demonstrate that the major cause of systemic inflammation and sepsis observed
      upon such treatments is activation of an opportunistic infection. Mice of the
      same strain (CBA) housed under SPF conditions do not develop the characteristic
      symptoms, nor do they become moribund. Yet, regardless of the breeding
      conditions, upon synergistic action of cyclophosphamide and dsDNA, CD34(+)
      hematopoietic stem cells consistently fail to give rise to lymphoid lineage
      progenitors. We demonstrate that this differentiation defect is reversible and
      that population of lymphoid progenitors is restored by day 29 after
      cyclophosphamide injection.

PMID- 26293797
TI  - Possible role of TGF beta1 in inflammatory pseudotumor associated with multiple
      neuroendocrine tumors of the small intestine.
AB  - INTRODUCTION: Inflammatory myofibroblastic tumors (IMTs), a rare condition of
      unknown etiology, have often been reported to be associated with specific
      infections or malignant tumors. The question of whether IMT themselves are an
      inflammatory or a neoplastic process is still going on. CASE REPORT: A 57-year
      old female patient was transferred to our hospital with ileus caused by a
      mesenterial tumor. Intraoperatively, the mesenteric mass and the dependent small
      intestine segment, as well as a suspect hepatic lesion, were resected. The
      histopathological investigation revealed 8 malignant neuroendocrine tumors (NET)
      of the small intestine with lymphatic and hepatic metastasis and a mesenteric
      IMT. The postoperative course was uneventful, and the patient was discharged on
      the 18th postoperative day. The last follow-up after 30 months showed no
      recurrence of the IMT but clinical and radiological evidence of a persistent
      hepatic metastasis of the NETs. While plasma Chromogranin A remained suppressed
      by Sandostatin, the TGF beta1 level was markedly elevated. DISCUSSION: Based on
      the current literature and our previous experiences, we can state that IPT are an
      aberrant secondary immunological process possibly induced by excessive TGF beta1
      and not a neoplasia. Nevertheless, the tumorous behavior points to a continuity
      between inflammation and neoplasia. Differential diagnoses and the potential
      molecular pathogenesis are further discussed.

PMID- 26293798
TI  - Tankyrase 2 (TNKS2) polymorphism associated with risk in developing non-small
      cell lung cancer in a Chinese population.
AB  - OBJECTIVES: We investigated the association between poly(ADP-ribose) polymerase
      Tankyrase 2 (TNKS2) single-nucleotide polymorphisms (SNPs) and the risk of
      developing non-small cell lung cancer (NSCLC) in a Han Chinese population.
      METHODS: Five-hundred NSCLC cases and 500 healthy controls were genotyped for
      four TNKS2 tagging SNPs (rs1538833, rs1538833, rs1340420, and rs1340420). The
      association between genotype and NSCLC risk was evaluated by computing the odds
      ratio (OR) and 95% confidence interval (CI) using multivariate unconditional
      logistic regression analyses. RESULTS: Individual alleles of the four TNKS2 SNPs
      were not associated with NSCLC risk in the studied Chinese population. However,
      patients carrying TNKS2 rs1340420 G/G and A/G genotypes were associated with a
      lower risk of developing NSCLC and adenocarcinoma (OR=0.14; 95% CI=0.02-1.15 and
      OR=0.11; 95% CI=0.03-0.91, respectively), whereas females patients homozygous for
      the TNKS2 rs1770474 T allele, a rare type, were associated with a higher risk of
      developing squamous-cell carcinoma (SCC) (OR=4.67; 95% CI=0.87-25.01).
      CONCLUSION: TNKS2 rs1340420 SNP was associated with lower NSCLC risk, whereas
      rs1770474 SNP was associated with higher SCC risk, suggesting that these two SNPs
      may be useful predictors of risk of developing NSCLC and SCC in this Chinese
      population.

PMID- 26293799
TI  - Cribriform-morular variant of papillary thyroid carcinoma.
AB  - Cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is a rare
      morphologic entity. This tumor is usually associated with familial adenomatous
      polyposis (FAP), but rarely may be sporadic. This neoplasm commonly occurs in
      young females. The majority of patients present with gradually enlarging painless
      neck mass. There is no specific imaging finding of CMV-PTC, and the diagnosis is
      exclusively made on pathologic examination. A multitude of cytologic features of
      CMV-PTC are described, which includes hypercellularity, cribriform pattern,
      papillary arrangement of tall columnar cells, morules, spindle cells, clear and
      ground-glass nuclei, hyaline material, hemosiderin-laden histiocytes, and absence
      of colloid in the background. CMV-PTC is histologically characterized by the
      papillary growth of tall columnar cells, cribriform pattern without colloid,
      spindle cells, squamoid morules, and nuclear clearing. The immunoreactivity for
      beta-catenin and biotin-positive nuclear clearing may indicate CMV-PTC. Total
      thyroidectomy for familial or lobectomy for sporadic cases is usually the
      treatment for CMV-PTC. It carries a better prognosis than the other aggressive
      variants of papillary thyroid carcinoma. In this review, we discuss the current
      knowledge on CMV-PTC and its clinical relevance. 

PMID- 26293800
TI  - Radiographic natural course of lumbar degenerative spondylolisthesis and its risk
      factors related to the progression and onset in a 15-year community-based cohort
      study: the Miyama study.
AB  - BACKGROUND: The natural history and risk factors for lumbar degenerative
      spondylolisthesis (DS) remain unclear. Because it is important for physicians to
      take these factors into account to ensure accurate decisions regarding surgical
      methods, this study aimed to elucidate the natural course and risk factors for
      the progression of DS. METHODS: This is a prospective observation and case
      control study of 15-year follow-up in a rural mountainous cohort in Wakayama,
      Japan. In 1990 and 2005, a total of 200 participants (baseline age, range 40-75)
      were subjected to anteroposterior and lateral radiographs of the lumbar spine,
      which were acquired with patients in a standing position. The prevalence of DS
      (slip >=3 mm) at baseline and the incidence of DS at 15-year follow-up were
      recorded. Risk factors at baseline for progression of L4 slip (>=3 mm) over the
      15-year period were determined by multiple logistic regression analysis. RESULTS:
      The overall prevalence of DS in 1990 was 10 % (20/200), and by spinal level was
      as follows: one case at L3, 14 cases at L4, and five at L5. In 2005, the overall
      prevalence of DS had risen to 22.5 % (45/200). Thus the incidence of de novo DS
      during the 15-year period was estimated at 14 % (25/180). Progression of the L4
      slip (>=3 mm), regardless of baseline condition, was observed in 23 participants
      after 15 years. In multiple regression analysis, significant risk factors for L4
      slip progression were identified as age less than 60 years, female sex, lumbar
      axis sacral distance, facet sagittalization, and existence of slip at baseline.
      CONCLUSIONS: We successfully elucidated the risk factors for the progression of
      DS in a general population. Moreover, the results of this study identified
      preventive factors as well as risk factors for slip progression. This study
      provides useful information for physicians treating DS.

PMID- 26293801
TI  - Opportunities for improvement: anticoagulation in patients undergoing total knee
      or hip replacement.
AB  - BACKGROUND: According to guidelines, initiation of pharmacological
      thromboprophylaxis after total knee or hip replacement is recommended and
      associated with improved patient outcomes. However, data on how these
      recommendations are followed in clinical practice are sparse. METHODS: All
      patients undergoing first-time total knee or hip replacement in Denmark 2008-2011
      were identified. By cross-referencing Danish nationwide registries, quantitative
      use of anticoagulants administered orally and subcutaneously post-discharge was
      assessed by number of claimed prescriptions after surgery. Logistic regression
      analysis was used to identify factors associated with initiation of prophylaxis.
      RESULTS: A total of 50,389 patients were included in the study (median age 69,
      inter-quartile range 62-76). Novel oral anticoagulants were initiated in 14.7 %
      of the patients and heparins/fondaparinux in 2.3 % of the patients. The use of
      anticoagulants increased from 6.3 % in 2008 to 30.0 % of patients in 2011. Among
      patients initiating prophylaxis with a novel oral anticoagulant post-discharge,
      almost all were treated according to guidelines in terms of treatment duration.
      Factors significantly associated with an increased chance of prophylaxis among
      total hip replacement patients were: age (per 10-year increments) and female
      gender. CONCLUSIONS: Use of pharmacological thromboprophylaxis after total knee
      or hip replacement was low, but increasing during the study period. This is
      probably due to increased availability of novel oral anticoagulants. Further
      initiatives to increase guideline recommended use of prophylactic anticoagulation
      after orthopaedic surgery are warranted.

PMID- 26293802
TI  - Hyperleptinemia suppresses aggravation of arthritis of collagen-antibody-induced
      arthritis in mice.
AB  - BACKGROUND: Leptin is an adipocytokine produced by adipocytes and controlling
      body weight. It is unclear whether leptin works as a proinflammatory or an anti
      inflammatory cytokine. We investigated the effects of hyperleptinemia on leptin
      transgenic (LepTg) mice in terms of cartilage destruction, bone destruction,
      joint synovitis, and serum cytokine levels by using a mouse model of collagen
      antibody-induced arthritis (CAIA). METHODS: CAIA was induced for female age
      matched 6- to 8-week-old C57BL/6 J control mice and LepTg mice. Mice were
      injected intraperitoneally with 5 mg of a combination of monoclonal antibody
      specific for type II collagen on day 0 and 12.5 mg of lipopolysaccharide (LPS) on
      day 3. Clinical evaluation of arthritis was monitored for 14 days, and hind paws
      were examined clinically and histologically. Serum cytokine levels of interleukin
      (IL)-1beta, IL-6, IL-10, and IL-17 and tumor necrosis factor alpha (TNF-alpha)
      were also analyzed on days 0 and 5. Moreover, THP-1 cells, which are human
      monocytic cell line derived from an acute monocytic leukemia patient, were
      cultured and differentiated into macrophages. The effects of leptin on messenger
      RNA (mRNA) expression of IL-6 were examined by real-time quantitative polymerase
      chain reaction (RT-PCR). RESULTS: Serum leptin concentrations were approximately
      ninefold higher in LepTg mice (62.0 +/- 20.7 ng/ml) than in control mice (7.2 +/-
      0.5 ng/ml). Severity of clinical paw swelling, arthritis score, synovial
      hyperplasia, and cartilage damage were suppressed in LepTg mice with CAIA.
      Although serum cytokine levels of IL-1beta, IL-17, and IL-10 and TNF-alpha showed
      no significant changes in two mice, serum levels of IL-6 in LepTg mice were
      suppressed at day 5. Moreover, in vitro study showed that IL-6 elevation
      following LPS exposure in THP-1 cells was suppressed with high leptin
      concentrations. CONCLUSION: Our finding suggests that hyperleptinemia suppress IL
      6 responses and progression of joint inflammation. Leptin may play an anti
      inflammatory role under hyperleptinemia.

PMID- 26293803
TI  - Bedaquiline and delamanid in tuberculosis.
AB  - INTRODUCTION: In recent years, a pressing need to develop new, effective and safe
      drugs against tuberculosis (TB) has continued. Poor adherence to a long
      therapeutic regimen against TB, intermittent drug use, errors in medical
      prescriptions, low quality of old TB drugs and ineffective TB control have led to
      the emergence of resistant TB. AREAS COVERED: Two new drugs have gained
      importance and seem promising against resistant TB: bedaquiline and delamanid.
      This review summarizes the main characteristics of these two drugs and their role
      in TB management. EXPERT OPINION: Bedaquiline and delamanid appear to be
      promising new anti-TB drugs. Due to a mechanism of action that is different from
      that of other available drugs, their efficacy has appeared optimal in cases of
      adults with resistant pulmonary TB. Although their pharmacokinetic and
      pharmacodynamic profiles seem optimal, potential cardiologic side effects such as
      QT-interval prolongation have been associated with their use. However, specific
      studies performed in the pediatric population are needed to confirm these
      results. This seems particularly important considering the long duration of TB
      treatment required for resistant TB as well as the potential interactions with
      other drugs included in anti-TB regimens or administered for an underlying
      comorbidity.

PMID- 26293804
TI  - TPGS/Phospholipids Mixed Micelles for Delivery of Icariside II to Multidrug
      Resistant Breast Cancer.
AB  - The biggest challenge for the treatment of multidrug resistant cancer is to
      deliver a high concentration of anticancer drugs to cancer cells. Icariside II is
      a flavonoid from Epimedium koreanum Nakai with remarkable anticancer properties,
      but poor solubility and significant efflux from cancer cells limited its clinical
      use. In our previous study, a self-assembled mixture of micelles (TPGS-Icariside
      II-phospholipid complex) was successfully constructed, which could substantially
      increase the solubility of Icariside II and inhibit the efflux on Caco-2 cells.
      In this study, we evaluate the anticancer effect of the mixed micelles
      encapsulating Icariside II (Icar-MC) on MCF-7/ADR, a multidrug-resistant breast
      cancer cell line. The cellular uptake of the micelles was confirmed by
      fluorescent coumarin-6-loaded micelles. The IC50 of Icar-MC in MCF-7/ADR was 2
      fold less than the free drug. The in vitro study showed Icar-MC induced more
      apoptosis and lactate dehydrogenase release. Intravenous injection of Icar-MC
      into nude mice bearing MCF-7/ADR xenograft resulted in a better antitumor
      efficacy compared with the administration of free drug, without causing
      significant body weight changes in mice. The antitumor effect was further
      verified by magnetic resonance imaging and immunohistochemical assays for Ki-67,
      a proliferative indicator. Moreover, Icar-MC treatment also elevated Bax/Bcl-2
      ratio and the expressions of cleaved caspase-3, -8, -9 and AIFM1 in tumors. This
      study suggests that phospholipid/TPGS mixed micelles might be a suitable drug
      delivery system for Icariside II to treat multidrug resistant breast cancer.

PMID- 26293805
TI  - Inhibition of 4NQO-Induced Oral Carcinogenesis by Dietary Oyster Shell Calcium.
AB  - Oyster has gained much attention recently for its anticancer activity but it is
      unclear whether calcium, the major antitumor ingredient in oyster shell, is
      responsible for the anticarcinogenic role of the oyster. To address this issue,
      C57BL/6 mice were fed with the carcinogen 4-nitroquinoline-1-oxide (4NQO, 50
      ug/mL) and normal diet or a diet containing oyster powder, oyster calcium, or
      calcium depleted oyster powder. The tongue tissue specimens isolated from these
      mice were histologically evaluated for hyperplasia, dysplasia, and papillary
      lesions, and then analyzed for proliferation and differentiation markers by
      immunohistochemistry. The results showed that mice on the diet containing oyster
      calcium significantly reduced rates of tumors in the tongue and proliferation and
      enhanced differentiation in the oral epithelium compared with the diet containing
      calcium depleted oyster powder. These results suggest that calcium in oyster
      plays a critical role in suppressing formation of oral squamous cell carcinoma
      and proliferation and promoting differentiation of the oral epithelium. 

PMID- 26293806
TI  - "A Somali girl is Muslim and does not have premarital sex. Is vaccination really
      necessary?" A qualitative study into the perceptions of Somali women in the
      Netherlands about the prevention of cervical cancer.
AB  - INTRODUCTION: Participation in Human Papillomavirus (HPV) vaccination and
      Papanicolaou Screening (Pap smears) is low among ethnic minorities in the
      Netherlands and hardly any information is available about the cervical cancer
      prevention methods of Somali women living in the diaspora. This qualitative
      study, based on the Health Belief Model (HBM) and an intersectionality-based
      framework, explores the perceptions of Somali women living in the Netherlands
      regarding measures to prevent cervical cancer. METHODS: Semi-structured
      interviews have been conducted with young Somali women aged 17-21 years (n = 14)
      and Somali mothers aged 30-46 years (n = 6). Two natural group discussions have
      been conducted with 12 and 14 Somali mothers aged 23-66 years. The collected data
      has been analyzed thematically for content. RESULTS: In this study, we have
      identified perceived barriers to the use of preventive measures across three
      major themes: (1) Somali women and preventive healthcare; (2) Language,
      knowledge, and negotiating decisions; and (3) Sexual standards, culture, and
      religion. Many issues have been identified across these themes, e.g., distrust of
      the Dutch health care system or being embarrassed to get Pap smears due to Female
      Genital Mutilation (FGM) and having a Dutch, male practitioner; or a perceived
      low susceptibility to HPV and cancer because of the religious norms that prohibit
      sex before marriage. CONCLUSIONS: Current measures in the Netherlands to prevent
      women from developing cervical cancer hardly reach Somali women because these
      women perceive these kinds of preventative measures as not personally relevant.
      Dutch education strategies about cervical cancer deviate from ways of exchanging
      information within the Somali community. Teachers can provide culturally
      sensitive information to young Somali women in schools. For Somali mothers, oral
      education (e.g., poetry or theater) about the Dutch health care system and men's
      roles in HPV transmission may be useful. An intersectional approach, grounded in
      the HBM, is recommended to promote equal access to preventive health care for
      Somali women.

PMID- 26293807
TI  - Copy number variation in exportin-4 (XPO4) gene and its association with
      histological severity of non-alcoholic fatty liver disease.
AB  - A recent genome-wide copy number (CNV) scan identified a 13q12.11 duplication in
      the exportin-4 (XPO4) gene to be associated with non-alcoholic steatohepatitis
      (NASH). We sought to confirm the finding in a larger cohort and to assess the
      serum XPO4 pattern in a broad spectrum of non-alcoholic fatty liver disease
      (NAFLD) cases. We analysed 249 NAFLD patients and 232 matched controls using
      TaqMan assay and serum XPO4 was measured. Copy number distribution was as
      follows: copy number neutral (NAFLD: 53.8%, controls: 68.6%), copy number losses
      (NAFLD: 13.3%, controls: 12.9%), copy number gains (NAFLD: 32.9%, controls:
      18.5%). CNV gain was significantly associated with a greater risk of NAFLD
      (adjusted OR 2.22, 95% CI 1.42-3.46, P = 0.0004) and NASH (adjusted OR 2.33, 95%
      CI 1.47-3.68, P = 0.0003). Interestingly, subjects carrying extra copy number
      showed significantly higher serum ALT and triglyceride (P < 0.05). Serum XPO4
      levels progressively declined (P = 0.043) from controls (24.6 ng/mL) to simple
      steatosis (20.8 ng/mL) to NASH (13.8 ng/mL). In conclusion, XPO4 CNV duplication
      was associated with histological severity of NAFLD, and accompanied by changes in
      serum XPO4 levels providing insights into NAFLD pathogenesis, and has the
      potential for biomarker development. 

PMID- 26293808
TI  - Role of gross tumor volume in the prognosis of non-small cell lung cancer treated
      with 3D conformal radiotherapy: a meta-analysis.
AB  - PURPOSE: Three-dimensional conformal radiotherapy (3D-CRT) has become widely
      applied in patients with non-small cell lung cancer (NSCLC), and gross tumor
      volume (GTV) is a reliable index for predicting prognosis in patients with NSCLC.
      This meta-analysis investigated the association between GTV and prognosis in
      patients with NSCLC after 3D-CRT. METHODS: Electronic bibliographic databases
      were searched to identify articles related to NSCLC and 3D-CRT. The search
      results were carefully screened, using predetermined selection criteria, to
      select the most relevant studies. Newcastle-Ottawa Scale criteria were applied by
      2 reviewers independently to evaluate the quality of the methodology of each
      included article., Based on GTV, each patient was assigned to either the study
      group (large GTV [>=112 cm(3)]) or the control group (small GTV [<112 cm(3)]),
      and the mean rates of overall survival (OS) and survival at 1, 3, and 5 years
      were calculated in each group. Summary hazard ratio (HR) with 95% CI was
      calculated. FINDINGS: The data from 10 cohort studies were incorporated into the
      current meta-analysis (1473 patients; study group, 773; control group, 700). The
      OS in the study group was significantly less than that in the control group (HR =
      1.52; 95% CI, 1.10-1.94; P < 0.01). The study and control groups also had
      significantly different survival rates at 1 year (HR = 1.27; 95% CI, 1.10-1.46, P
      = 0.01), 3 years (HR = 2.06; 95% CI, 1.63-2.61; P < 0.01), and 5 years (HR =
      2.25; 95% CI, 1.63-3.10; P < 0.01). Findings from funnel plots and Egger tests of
      the OS and 3-year survival rate suggested no publication bias. With respect to
      the 1- and 5-year survival rates, however, the funnel plots and Egger tests
      demonstrated publication bias among the included studies. IMPLICATIONS: The
      relatively small number of studies and small sample size, as well as the lack of
      a specific and standard method of defining small and large GTV, may have
      influenced the credibility and reliability of our results. The findings suggest
      that GTV influences prognosis in patients with NSCLC after 3D-CRT. However,
      further studies with larger sample sizes are needed to confirm our finding that a
      larger GTV is negatively associated with NSCLC prognosis after 3D-CRT.

PMID- 26293810
TI  - Facile Synthesis of Single Crystal Vanadium Disulfide Nanosheets by Chemical
      Vapor Deposition for Efficient Hydrogen Evolution Reaction.
AB  - A facile chemical vapor deposition method to prepare single-crystalline VS2
      nanosheets for the hydrogen evolution reaction is reported. The electrocatalytic
      hydrogen evolution reaction (HER) activities of VS2 show an extremely low
      overpotential of -68 mV at 10 mA cm(-2), small Tafel slopes of ~34 mV decade(-1),
      as well as high stability, demonstrating its potential as a candidate non-noble
      metal catalyst for the HER.

PMID- 26293809
TI  - Intracellular amyloid beta oligomers impair organelle transport and induce
      dendritic spine loss in primary neurons.
AB  - INTRODUCTION: Synaptic dysfunction and intracellular transport defects are early
      events in Alzheimer's disease (AD). Extracellular amyloid beta (Abeta) oligomers
      cause spine alterations and impede the transport of proteins and organelles such
      as brain-derived neurotrophic factor (BDNF) and mitochondria that are required
      for synaptic function. Meanwhile, intraneuronal accumulation of Abeta precedes
      its extracellular deposition and is also associated with synaptic dysfunction in
      AD. However, the links between intracellular Abeta, spine alteration, and
      mechanisms that support synaptic maintenance such as organelle trafficking are
      poorly understood. RESULTS: We compared the effects of wild-type and Osaka
      (E693Delta)-mutant amyloid precursor proteins: the former secretes Abeta into
      extracellular space and the latter accumulates Abeta oligomers within cells.
      First we investigated the effects of intracellular Abeta oligomers on dendritic
      spines in primary neurons and their tau-dependency using tau knockout neurons. We
      found that intracellular Abeta oligomers caused a reduction in mushroom, or
      mature spines, independently of tau. We also found that intracellular Abeta
      oligomers significantly impaired the intracellular transport of BDNF,
      mitochondria, and recycling endosomes: cargoes essential for synaptic
      maintenance. A reduction in BDNF transport by intracellular Abeta oligomers was
      also observed in tau knockout neurons. CONCLUSIONS: Our findings indicate that
      intracellular Abeta oligomers likely contribute to early synaptic pathology in AD
      and argue against the consensus that Abeta-induced spine loss and transport
      defects require tau.

PMID- 26293813
TI  - On health governance and (in)equity.

PMID- 26293811
TI  - Exometabolom analysis of breast cancer cell lines: Metabolic signature.
AB  - Cancer cells show characteristic effects on cellular turnover and DNA/RNA
      modifications leading to elevated levels of excreted modified nucleosides. We
      investigated the molecular signature of different subtypes of breast cancer cell
      lines and the breast epithelial cell line MCF-10A. Prepurification of cell
      culture supernatants was performed by cis-diol specific affinity chromatography
      using boronate-derivatized polyacrylamide gel. Samples were analyzed by
      application of reversed phase chromatography coupled to a triple quadrupole mass
      spectrometer. Collectively, we determined 23 compounds from RNA metabolism, two
      from purine metabolism, five from polyamine/methionine cycle, one from histidine
      metabolism and two from nicotinate and nicotinamide metabolism. We observed major
      differences of metabolite excretion pattern between the breast cancer cell lines
      and MCF-10A, just as well as between the different breast cancer cell lines
      themselves. Differences in metabolite excretion resulting from cancerous
      metabolism can be integrated into altered processes on the cellular level.
      Modified nucleosides have great potential as biomarkers in due consideration of
      the heterogeneity of breast cancer that is reflected by the different molecular
      subtypes of breast cancer. Our data suggests that the metabolic signature of
      breast cancer cell lines might be a more subtype-specific tool to predict breast
      cancer, rather than a universal approach. 

PMID- 26293812
TI  - Influence of parental factors on adolescents' transition to first sexual
      intercourse in Nairobi, Kenya: a longitudinal study.
AB  - BACKGROUND: Several studies have demonstrated a link between young people's
      sexual behavior and levels of parental monitoring, parent-child communication,
      and parental discipline in Western countries. However, little is known about this
      association in African settings, especially among young people living in high
      poverty settings such as urban slums. The objective of the study was to assess
      the influence of parental factors (monitoring, communication, and discipline) on
      the transition to first sexual intercourse among unmarried adolescents living in
      urban slums in Kenya. METHODS: Longitudinal data collected from young people
      living in two slums in Nairobi, Kenya were used. The sample was restricted to
      unmarried adolescents aged 12-19 years at Wave 1 (weighted n = 1927). Parental
      factors at Wave 1 were used to predict adolescents' transition to first sexual
      intercourse by Wave 2. Relevant covariates including the adolescents' age, sex,
      residence, school enrollment, religiosity, delinquency, and peer models for risk
      behavior were controlled for. Multivariate logistic regression models were used
      to assess the associations of interest. All analyses were conducted using Stata
      version 13. RESULTS: Approximately 6% of our sample transitioned to first sexual
      intercourse within the one-year study period; there was no sex difference in the
      transition rate. In the multivariate analyses, male adolescents who reported
      communication with their mothers were less likely to transition to first sexual
      intercourse compared to those who did not (p < 0.05). This association persisted
      even after controlling for relevant covariates (OR: <=0.33; p < 0.05). However,
      parental monitoring, discipline, and communication with their fathers did not
      predict transition to first sexual intercourse for male adolescents. For female
      adolescents, parental monitoring, discipline, and communication with fathers
      predicted transition to first sexual intercourse; however, only communication
      with fathers remained statistically significant after controlling for relevant
      covariates (OR: 0.30; 95% C.I.: 0.13-0.68). CONCLUSION: This study provides
      evidence that cross-gender communication with parents is associated with a delay
      in the onset of sexual intercourse among slum-dwelling adolescents. Targeted
      adolescent sexual and reproductive health programmatic interventions that include
      parents may have significant impacts on delaying sexual debut, and possibly
      reducing sexual risk behaviors, among young people in high-risk settings such as
      slums.

PMID- 26293814
TI  - Electronic cigarette use in young people in Great Britain 2013-2014.
AB  - OBJECTIVES: The recent growth in the market for electronic cigarettes (e
      cigarettes) has led to concerns over their use by young people. It is therefore
      important to examine trends in the perception and use of e-cigarettes and
      conventional cigarettes in this group. STUDY DESIGN: Two-wave cross-sectional
      survey design. METHODS: Young people aged 11-18 in Great Britain were surveyed
      online by YouGov in 2013 and 2014. Use of e-cigarettes, together with perceived
      health harms and intention to use were assessed and compared in relation to
      cigarette smoking history, age and gender. RESULTS: Ever-use of e-cigarettes
      increased significantly from 4.6% (95% CI 3.8-5.7) in 2013 to 8.2% (95% CI 7.0
      9.6) in 2014. Monthly or more use of e-cigarettes increased from 0.9% (95% CI 0.5
      1.5) to 1.7 (1.2-2.4), but remained rare in never-smokers at under 0.2%. The
      proportion of young people who perceived e-cigarettes to be less harmful to users
      than cigarettes fell from 73.4% (95% CI 71.0-75.8) to 66.9% (95% CI 64.5-69.2),
      while the proportion who considered e-cigarettes to cause similar levels of harm
      increased from 11.8% (95% CI 10.0-13.5) to 18.2% (95% CI 16.3-20.1). Of the 8.2%
      of e-cigarette ever-users in 2014, 69.8% (95% CI 62.2%-77.3%) had smoked a
      cigarette prior to using an e-cigarette, while 8.2% (95% CI 4.1%-12.2%) first
      smoked a cigarette after e-cigarette use. CONCLUSIONS: A growing proportion of
      young people in Great Britain believe e-cigarettes are as harmful as smoking
      tobacco. Use of e-cigarettes by young people is increasing, but is largely
      confined to those who smoke.

PMID- 26293816
TI  - Ultra-Structural Alterations in In Vitro Produced Four-Cell Bovine Embryos
      Following Controlled Slow Freezing or Vitrification.
AB  - Cryopreservation is the process of freezing and preserving cells and tissues at
      low temperatures. Controlled slow freezing and vitrification have successfully
      been used for cryopreservation of mammalian embryos. We investigated the effect
      of these two cryopreservation methods on in vitro produced four-cell stage bovine
      embryos which were classified according to their quality and separated into three
      groups. The first group was maintained as untreated controls (n = 350). Embryos
      of the second (n = 385) and the third (n = 385) groups were cryopreserved either
      by controlled slow freezing or by vitrification. Embryos in groups 2 and 3 were
      thawed after 1 day. Hundred embryos were randomly selected from the control
      group, and 100 morphologically intact embryos from the second and third group
      were thawed after 1 day and cultured to observe the development up to the
      blastocyst stage. The blastocyst development rate was 22% in the control group,
      1% in the slow-freezing group and 3% in the vitrification group. Remaining
      embryos of all three groups were examined by light microscopy, transmission
      electron microscopy and immunofluorescence confocal microscopy with subsequent
      histological staining procedures. Cryopreservation caused degenerative changes at
      the ultra-structural level. Compared with vitrification, slow freezing caused an
      increased mitochondrial degeneration, cytoplasmic vacuolization, disruption of
      the nuclear and plasma membrane integrity, organelle disintegration, cytoskeletal
      damage, a reduced thickness of the zona pellucida and a formation of fractures in
      the zona pellucida. Further studies are required to understand and decrease the
      harmful effects of cryopreservation. 

PMID- 26293815
TI  - A community resource of experimental data for NMR / X-ray crystal structure
      pairs.
AB  - We have developed an online NMR / X-ray Structure Pair Data Repository. The NIGMS
      Protein Structure Initiative (PSI) has provided many valuable reagents, 3D
      structures, and technologies for structural biology. The Northeast Structural
      Genomics Consortium was one of several PSI centers. NESG used both X-ray
      crystallography and NMR spectroscopy for protein structure determination. A key
      goal of the PSI was to provide experimental structures for at least one
      representative of each of hundreds of targeted protein domain families. In some
      cases, structures for identical (or nearly identical) constructs were determined
      by both NMR and X-ray crystallography. NMR spectroscopy and X-ray diffraction
      data for 41 of these "NMR / X-ray" structure pairs determined using conventional
      triple-resonance NMR methods with extensive sidechain resonance assignments have
      been organized in an online NMR / X-ray Structure Pair Data Repository. In
      addition, several NMR data sets for perdeuterated, methyl-protonated protein
      samples are included in this repository. As an example of the utility of this
      repository, these data were used to revisit questions about the precision and
      accuracy of protein NMR structures first outlined by Levy and coworkers several
      years ago (Andrec et al., Proteins 2007;69:449-465). These results demonstrate
      that the agreement between NMR and X-ray crystal structures is improved using
      modern methods of protein NMR spectroscopy. The NMR / X-ray Structure Pair Data
      Repository will provide a valuable resource for new computational NMR methods
      development.

PMID- 26293817
TI  - Sudden and Fatal Malfunction of a Durata Defibrillator Lead due to External
      Insulation Failure.
AB  - Defibrillator lead malfunction can be a disastrous complication, leading to loss
      of protection from sudden cardiac death in a high-risk patient population.
      Recognition of lead-specific risk for failure can assist in development of
      focused screening or surveillance, as in the case of the Riata lead (St. Jude
      Medical, St. Paul, MN, USA) or the Sprint Fidelis lead (Medtronic Inc.,
      Minneapolis, MN, USA). A case of defibrillation failure secondary to a Durata
      lead insulation failure is presented. A brief review of the literature and
      current St. Jude Medical implantable cardiac defibrillator lead design is
      presented. Identification of arcing is identified as a potential sign of
      catastrophic insulation failure. 

PMID- 26293819
TI  - Oxidative Stress and Metabolism: The NF-Erythroid 2 p45-Related Factor 2:Kelch
      like ECH-Associated Protein 1 System and Regulatory T Lymphocytes in Ischemic
      AKI.

PMID- 26293818
TI  - Recent insights into the morphological diversity in the amniote primary and
      secondary palates.
AB  - The assembly of the upper jaw is a pivotal moment in the embryonic development of
      amniotes. The upper jaw forms from the fusion of the maxillary, medial nasal, and
      lateral nasal prominences, resulting in an intact upper lip/beak and nasal
      cavities; together called the primary palate. This process of fusion requires a
      balance of proper facial prominence shape and positioning to avoid craniofacial
      clefting, whilst still accommodating the vast phenotypic diversity of adult
      amniotes. As such, variation in craniofacial ontogeny is not tolerated beyond
      certain bounds. For clarity, we discuss primary palatogenesis of amniotes into in
      two categories, according to whether the nasal and oral cavities remain connected
      throughout ontogeny or not. The transient separation of these cavities occurs in
      mammals and crocodilians, while remaining connected in birds, turtles and
      squamates. In the latter group, the craniofacial prominences fuse around a
      persistent choanal groove that connects the nasal and oral cavities.
      Subsequently, all lineages except for turtles, develop a secondary palate that
      ultimately completely or partially separates oral and nasal cavities. Here, we
      review the shared, early developmental events and highlight the points at which
      development diverges in both primary and secondary palate formation.

PMID- 26293820
TI  - T Lymphocyte-Specific Activation of Nrf2 Protects from AKI.
AB  - T lymphocytes are established mediators of ischemia reperfusion (IR)-induced AKI,
      but traditional immune principles do not explain their mechanism of early action
      in the absence of alloantigen. Nrf2 is a transcription factor that is crucial for
      cytoprotective gene expression and is generally thought to have a key role in
      dampening IR-induced AKI through protective effects on epithelial cells. We
      proposed an alternative hypothesis that augmentation of Nrf2 in T cells is
      essential to mitigate oxidative stress during IR-induced AKI. We therefore
      generated mice with genetically amplified levels of Nrf2 specifically in T cells
      and examined the effect on antioxidant gene expression, T cell activation,
      cytokine production, and IR-induced AKI. T cell-specific augmentation of Nrf2
      significantly increased baseline antioxidant gene expression. These mice had a
      high frequency of intrarenal CD25(+)Foxp3(+) regulatory T cells and decreased
      frequencies of CD11b(+)CD11c(+) and F4/80(+) cells. Intracellular levels of TNF
      alpha, IFN-gamma, and IL-17 were significantly lower in CD4(+) T cells with high
      Nrf2 expression. Mice with increased T cell expression of Nrf2 were significantly
      protected from functional and histologic consequences of AKI. Furthermore,
      adoptive transfer of high-Nrf2 T cells protected wild-type mice from IR injury
      and significantly improved their survival. These data demonstrate that T cell
      specific activation of Nrf2 protects from IR-induced AKI, revealing a novel
      mechanism of tissue protection during acute injury responses. 

PMID- 26293823
TI  - Donor-Specific HLA Antibody IgG Subclasses Are Associated with Phenotypes of
      Antibody-Mediated Rejection in Sensitized Renal Allograft Recipients.

PMID- 26293824
TI  - A workable model for the management of hyperglycemia in non-critically ill
      patients in an Asian population.
AB  - OBJECTIVE: The clinical efficacy of applying a western model for managing
      hyperglycemia in hospitalized patients in Asia has not been studied. METHODS: For
      this observational case-control study, we divided six medical wards into two
      groups, an intervention group and a control group. The intervention group,
      consisting three medical wards on the same floor, received care under a computer
      assisted consulting model in which special care was automatically indicated for
      patients who had two successive high glucose measurements in 1 day. The control
      group, consisting of another three medical wards distributed on different floors,
      received regular care. Outcome measures were baseline and post-intervention
      patient-day weighted mean glucose, percentage of patient-day weighted glucose
      >=180 mg/dL, proportion of glucose level 100-180 mg/dL, and prevalence of
      inpatient hyperglycemia (>180 mg/dL) and hypoglycemia (individual measurement <70
      mg/dL and patient-day with any measurement <70 mg/dL). RESULTS: At baseline, the
      patient-day weighted mean glucose level was 181.6 mg/dL. All parameters were
      comparable between the intervention and control groups with the exception of
      prevalence of hypoglycemia, which was found to be higher in the intervention
      group. After intervention, patient-day weighted mean glucose levels for
      intervention and control groups were 169.9 mg/dL and 176.7 mg/dL, respectively (p
      < 0.001). The intervention group had a reduction in hypoglycemia and the control
      group an increase. CONCLUSION: This computer-assisted consulting model was found
      to be potentially very workable for the management of inpatient hyperglycemia in
      hospitals with high patient volumes in Asia.

PMID- 26293821
TI  - Hepcidin as a Major Component of Renal Antibacterial Defenses against
      Uropathogenic Escherichia coli.
AB  - The iron-regulatory peptide hepcidin exhibits antimicrobial activity. Having
      previously shown hepcidin expression in the kidney, we addressed its role in
      urinary tract infection (UTI), which remains largely unknown. Experimental UTI
      was induced in wild-type (WT) and hepcidin-knockout (Hepc-/-) mice using the
      uropathogenic Escherichia coli CFT073 strain. Compared with infected WT mice,
      infected Hepc-/- mice showed a dramatic increase in renal bacterial load.
      Moreover, bacterial invasion was significantly dampened by the pretreatment of WT
      mice with hepcidin. Infected Hepc-/- mice exhibited decreased iron accumulation
      in the renal medulla and significant attenuation of the renal inflammatory
      response. Notably, we demonstrated in vitro bacteriostatic activity of hepcidin
      against CFT073. Furthermore, CFT073 repressed renal hepcidin, both in vivo and in
      cultured renal cells, and reduced phosphorylation of SMAD kinase in vivo,
      suggesting a bacterial strategy to escape the antimicrobial activities of
      hepcidin. In conclusion, we provide new mechanisms by which hepcidin contributes
      to renal host defense and suggest that targeting hepcidin offers a strategy to
      prevent bacterial invasion. 

PMID- 26293822
TI  - IgG Donor-Specific Anti-Human HLA Antibody Subclasses and Kidney Allograft
      Antibody-Mediated Injury.
AB  - Antibodies may have different pathogenicities according to IgG subclass. We
      investigated the association between IgG subclasses of circulating anti-human HLA
      antibodies and antibody-mediated kidney allograft injury. Among 635 consecutive
      kidney transplantations performed between 2008 and 2010, we enrolled 125 patients
      with donor-specific anti-human HLA antibodies (DSA) detected in the first year
      post-transplant. We assessed DSA characteristics, including specificity, HLA
      class specificity, mean fluorescence intensity (MFI), C1q-binding, and IgG
      subclass, and graft injury phenotype at the time of sera evaluation. Overall, 51
      (40.8%) patients had acute antibody-mediated rejection (aABMR), 36 (28.8%)
      patients had subclinical ABMR (sABMR), and 38 (30.4%) patients were ABMR-free.
      The MFI of the immunodominant DSA (iDSA, the DSA with the highest MFI level) was
      6724+/-464, and 41.6% of patients had iDSA showing C1q positivity. The
      distribution of iDSA IgG1-4 subclasses among the population was 75.2%, 44.0%,
      28.0%, and 26.4%, respectively. An unsupervised principal component analysis
      integrating iDSA IgG subclasses revealed aABMR was mainly driven by IgG3 iDSA,
      whereas sABMR was driven by IgG4 iDSA. IgG3 iDSA was associated with a shorter
      time to rejection (P<0.001), increased microcirculation injury (P=0.002), and C4d
      capillary deposition (P<0.001). IgG4 iDSA was associated with later allograft
      injury with increased allograft glomerulopathy and interstitial fibrosis/tubular
      atrophy lesions (P<0.001 for all comparisons). Integrating iDSA HLA class
      specificity, MFI level, C1q-binding status, and IgG subclasses in a Cox survival
      model revealed IgG3 iDSA and C1q-binding iDSA were strongly and independently
      associated with allograft failure. These results suggest IgG iDSA subclasses
      identify distinct phenotypes of kidney allograft antibody-mediated injury. 

PMID- 26293825
TI  - Dermoscopic changes in melanocytic nevi in patients receiving immunosuppressive
      and biologic treatments: results of a prospective case-control study.
AB  - BACKGROUND: The immune system restrains benign melanocytic lesions, however the
      relationship between immunosuppression and changes in nevi is not known.
      OBJECTIVES: We sought to investigate the development of new nevi in patients
      using immunosuppressive agents, to evaluate any size or dermoscopic changes in
      existent nevi, and to evaluate any risk of developing melanoma. METHODS: There
      were 266 melanocytic lesions in 103 patients undergoing immunosuppressive therapy
      and 180 melanocytic lesions matched for age, sex, race, and Fitzpatrick skin type
      in 60 healthy control subjects. RESULTS: Nevus counts increased from baseline in
      the treatment group (P < .001) as did nevus size (P = .046) but the increase
      compared with the control group only remained statistically significant for nevus
      numbers (P = .001). There was a statistically significant appearance of
      dermoscopic changes in the nevi of immunosuppressed patients compared with
      healthy control subjects (P < .001). Ten lesions were excised including 6 because
      of significant dermoscopic change during treatment and all were benign.
      LIMITATIONS: Follow-up duration was short and the number of patients was small.
      CONCLUSION: Immunosuppressive therapy was associated with increased nevus counts
      and changed dermoscopic appearance but as none of the changed and subsequently
      excised nevi were malignant, continued monitoring for invasive features is a
      reasonable alternative to excision.

PMID- 26293826
TI  - Preparation of solid-solution type Fe-Co nanoalloys by synchronous deposition of
      Fe and Co using dual arc plasma guns.
AB  - We succeeded in the efficient preparation of well-dispersed Fe-Co nanoalloys
      (NAs) using the arc plasma deposition method. Synchronous shots of dual arc
      plasma guns were applied to a carbon support to prepare the solid-solution type
      Fe-Co NAs having an approximately 1 : 1 atomic ratio. The alloy structures with
      and without a reductive thermal treatment under a hydrogen atmosphere were
      examined using X-ray powder diffraction, scanning transmission electron
      microscopy (STEM) combined with energy-dispersive X-ray analysis, high resolution
      STEM, and magnetic measurements, suggesting that highly crystalline spherical
      particles of ordered B2-type Fe-Co NAs form by the thermal treatment of the
      deposited grains.

PMID- 26293828
TI  - How incorrect is the use of adrenaline auto-injectors?

PMID- 26293827
TI  - Test-retest reproducibility of [(11)C]PBR28 binding to TSPO in healthy control
      subjects.
AB  - PURPOSE: The PET radioligand [(11)C]PBR28 binds to the translocator protein
      (TSPO), a marker of brain immune activation. We examined the reproducibility of
      [(11)C]PBR28 binding in healthy subjects with quantification on a regional and
      voxel-by-voxel basis. In addition, we performed a preliminary analysis of diurnal
      changes in TSPO availability. METHODS: Twelve subjects were examined using a high
      resolution research tomograph and [(11)C]PBR28, six in the morning and afternoon
      of the same day, and six in the morning on two separate days. Regional volumes of
      distribution (V T) were derived using a region-of-interest based two-tissue
      compartmental analysis (2TCM), as well as a parametric approach. Metabolite
      corrected arterial plasma was used as input function. RESULTS: For the whole
      sample, the mean absolute variability in V T in the grey matter (GM) was 18.3 +/-
      12.7 %. Intraclass correlation coefficients in GM regions ranged from 0.90 to
      0.94. Reducing the time of analysis from 91 to 63 min yielded a variability of
      16.9 +/- 14.9 %. There was a strong correlation between the parametric and 2TCM
      derived GM values (r = 0.99). A significant increase in GM V T was observed
      between the morning and afternoon examinations when using secondary methods of
      quantification (p = 0.028). In the subjects examined at the same time of the day,
      the absolute variability was 15.9 +/- 12.2 % for the 91-min 2TCM data.
      CONCLUSION: V T of [(11)C]PBR28 binding showed medium reproducibility and high
      reliability in GM regions. Our findings support the use of parametric approaches
      for determining [(11)C]PBR28 V T values, and indicate that the acquisition time
      could be shortened. Diurnal changes in TSPO binding in the brain may be a
      potential confounder in clinical studies and should be investigated further.

PMID- 26293829
TI  - Antibiotic treatment strategies for community-acquired pneumonia in adults.

PMID- 26293830
TI  - Barley landraces are characterized by geographically heterogeneous genomic
      origins.
AB  - BACKGROUND: The genetic provenance of domesticated plants and the routes along
      which they were disseminated in prehistory have been a long-standing source of
      debate. Much of this debate has focused on identifying centers of origins for
      individual crops. However, many important crops show clear genetic signatures of
      multiple domestications, inconsistent with geographically circumscribed centers
      of origin. To better understand the genetic contributions of wild populations to
      domesticated barley, we compare single nucleotide polymorphism frequencies from
      803 barley landraces to 277 accessions from wild populations. RESULTS: We find
      that the genetic contribution of individual wild populations differs across the
      genome. Despite extensive human movement and admixture of barley landraces since
      domestication, individual landrace genomes indicate a pattern of shared ancestry
      with geographically proximate wild barley populations. This results in landraces
      with a mosaic of ancestry from multiple source populations rather than discrete
      centers of origin. We rule out recent introgression, suggesting that these
      contributions are ancient. The over-representation in landraces of genomic
      segments from local wild populations suggests that wild populations contributed
      locally adaptive variation to primitive varieties. CONCLUSIONS: This study
      increases our understanding of the evolutionary process associated with the
      transition from wild to domesticated barley. Our findings indicate that
      cultivated barley is comprised of multiple source populations with unequal
      contributions traceable across the genome. We detect putative adaptive variants
      and identify the wild progenitor conferring those variants.

PMID- 26293831
TI  - Cost-effective optimization of real-time PCR-based detection of Campylobacter and
      Salmonella with inhibitor tolerant DNA polymerases.
AB  - AIMS: The aim of this study was to cost-effectively improve detection of
      foodborne pathogens in PCR inhibitory samples through the use of alternative DNA
      polymerases. METHODS AND RESULTS: Commercially available polymerases (n = 16) and
      PCR master mixes (n = 4) were screened on DNA purified from bacterial cells in
      two validated real-time PCR assays for Campylobacter and Salmonella. The five
      best performing (based on: limit of detection (LOD), maximum fluorescence, shape
      of amplification curves and amplification efficiency) were subsequently applied
      to meat and faecal samples. The VeriQuest qPCR master mix performed best for both
      meat and faecal samples (LODs of 10(2) and 10(4) CFU ml(-1) in the purest and
      crudest DNA extractions respectively) compared with Tth (LOD = 10(2)-10(3) and
      10(5)-10(6) CFU ml(-1)). AmpliTaqGold and HotMasterTaq both performed well (LOD =
      10(2)-10(4) CFU ml(-1)) with meat samples and poorly (LOD = 10(3)-10(6) CFU ml(
      1)/not detected) with faecal samples. CONCLUSIONS: Applying the VeriQuest qPCR
      master mix in the two tested real-time PCR assays could allow for simpler sample
      preparation and thus a reduction in cost. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This work exemplifies a cost-effective strategy for optimizing real-time PCR
      based assays. However, a DNA polymerase suitable for one assay and sample type is
      not necessarily optimal for other assays or sample types.

PMID- 26293832
TI  - Corrigendum: Processing of visually evoked innate fear by a non-canonical
      thalamic pathway.

PMID- 26293833
TI  - Increased circulating adiponectin in males with chronic HCV hepatitis.
AB  - BACKGROUND: Increased levels of adiponectin, a major adipokine with insulin
      sensitizing properties showing a strong sexual dimorphism, have been reported in
      individuals with chronic HCV infection (CHC), but data are limited by small
      samples and lack of control for the genetic background and hepatic fibrosis. The
      aim of this study was to compare adiponectin levels between CHC patients and
      accurately matched controls. METHODS: We considered 184 CHC patients, matched
      (1:1) for age, gender, body mass index, and Adiponectin genotype (ADIPOQ) with
      healthy individuals. To control for the severity of liver disease, a second
      control group consisting of 95 patients with histological nonalcoholic fatty
      liver disease (NAFLD) further matched (1:1) for severe fibrosis was exploited.
      ADIPOQ genotype was evaluated by Taqman assays, serum adiponectin measured by
      ELISA. RESULTS: Serum adiponectin was higher in CHC patients than in healthy
      individuals (9.0+/-5.0 MUg/ml vs. 7.3+/-4.0 MUg/ml; p=0.001; adjusted estimate
      +1.8, 1.7-2.9; p=0.001), and than in NAFLD patients (8.3+/-4.5 MUg/ml vs. 6.0+/
      4.2 MUg/ml; p<0.001; adjusted estimate +0.8, 0.2-1.4, p=0.006). After
      stratification for sex, serum adiponectin was higher in males with CHC than in
      healthy individuals and NAFLD patients (p<0.005 for both), whereas the difference
      was not significant in females. CONCLUSIONS: CHC is associated with increased
      serum adiponectin independently of age, body mass, diabetes, ADIPOQ genotype, and
      of severe liver fibrosis, particularly in men.

PMID- 26293834
TI  - Rituximab in autoimmune thrombotic thrombocytopenic purpura: A success story.
AB  - Despite a significant improvement of thrombotic thrombocytopenic purpura (TTP)
      prognosis since the use of plasma exchange, morbidity and mortality remained
      significant because of poor response to standard treatment or exacerbations and
      relapses. Rituximab, a chimeric monoclonal antibody directed against the B
      lymphocyte CD20 antigen, has shown a particular interest in this indication.
      Recent studies also reported strong evidence for its efficiency in the prevention
      of relapses. This review addresses these recent progresses and still opened
      questions in this topic: should rituximab be proposed in all patients at the
      acute phase? Should all patients benefit from a preemptive treatment? Is the
      infectious risk acceptable in this context? 

PMID- 26293835
TI  - Biphenotypic Primary Liver Carcinomas: Assessing Outcomes of Hepatic Directed
      Therapy.
AB  - BACKGROUND: Primary liver carcinomas with hepatocellular and cholangiocellular
      differentiation (b[HB]-PLC) are rare. Surgery offers the best prognosis, but
      there is a paucity of literature to guide therapy for patients with advanced or
      unresectable disease. This study aimed to evaluate outcomes of hepatic-directed
      therapy compared with those of systemic chemotherapy and surgery. METHODS: A
      retrospective evaluation of patients with b(HB)-PLC from 1 January 2008 to 1
      September 2014 was conducted. The patients were divided into the following four
      groups: transplantation (TX) group, surgical resection (SX) group, hepatic
      directed (HD) group, and systemic chemotherapy alone (SC) group. Overall and
      progression-free survival, treatment response, and clinicopathologic data were
      analyzed. RESULTS: The study included 79 patients (37 females) with an average
      age of 62 years. The number of patients in each group were as follows: TX group
      (n = 6), SX group (n = 27), HD group (n = 18), and SC group (n = 28). The mean
      follow-up periods were 33 months for the TX group, 17 months for the SX group, 14
      months for the HD group, and 7 months for the SX group. Overall, 28 % of the
      patients had cirrhosis and 35 % had viral hepatitis. The candidates for surgery
      comprised 42 % of the patients. The HD group (n = 18) had a significantly greater
      objective response than the SC group (n = 28) (47 vs. 6 %; p = 0.02). Two
      patients who underwent hepatic arterial infusion pump treatment were downstaged
      to resection. A trend toward improved OS/PFS was observed in the HD group versus
      the SC group, although statistically significant. The SX group had significantly
      improved survival (p < 0.001) as did the transplanted patients. CONCLUSIONS:
      Although surgery offers the best survival for b(HB)-PLC patients, only a minority
      are candidates for surgery. Because HD therapy showed a superior objective
      response over SC therapy, it may offer a survival advantage and may downstage
      patients for surgical resection or transplantation.

PMID- 26293836
TI  - A Patent Cranial End of the Ductus Venosus Can Result in Hemorrhage when
      Performing a Lesser Omentectomy-Omental Bursectomy Procedure.
AB  - BACKGROUND: In the surgical management of peritoneal metastases, a complete
      cytoreduction with all visible tumor removed is a necessary part of successful
      long-term management. One peritonectomy procedure that is occasionally
      accompanied by hemorrhage is the lesser omentectomy-omental bursectomy procedure.
      In the past, the cause of this unforeseen complication of cytoreductive surgery
      was not understood. METHODS: The anatomy of the lesser omentectomy-omental
      bursectomy procedure was reviewed. The bleeding was determined to be originating
      from the superior aspect of the omental bursa and intimately associated with the
      left hepatic vein. RESULTS: In performing this peritonectomy, it is necessary to
      clear the fissure defined by segments 2 and 3 of the liver with the left caudate
      lobe of the liver. This is the fissure defined by the ligamentum venosum. In
      dissecting the ligamentum venosum to its cranial end, this structure was found to
      be patent at its entrance into the left hepatic vein in some patients. Removal of
      the specimen requires transection of the ligamentum venosum as it enters the left
      hepatic vein. Transection of the ligament venosum at its cranial end can result
      in hemorrhage as a part of the lesser omentectomy-omental bursectomy procedure.
      CONCLUSIONS: The ligamentum venosum should be identified within the fissure where
      it is anatomically located. As the specimen is removed from the superior aspect
      of the omental bursa, the attachments between the ligamentum venosum and the left
      hepatic vein should be ligated prior to the transection.

PMID- 26293837
TI  - Perioperative Blood Transfusion and the Prognosis of Pancreatic Cancer Surgery:
      Systematic Review and Meta-analysis.
AB  - BACKGROUND: Perioperative blood transfusion (PBT) is common in pancreatic
      surgery. Recent studies have suggested that PBT may be associated with worse long
      term outcomes. METHODS: A systematic review and meta-analysis of studies
      comparing long-term clinical outcomes of cancer patients undergoing curative
      intent pancreatic surgery with regard to occurrence of PBT was performed.
      RESULTS: A total of 23 studies (4339 patients) were included in the systematic
      review, and 19 studies (3646 patients) were included in the meta-analysis. Nearly
      half (45.8 %) of all patients were female (range 25-60 %), and median age ranged
      from 59 to 72 years. About half (46.5 %, range 19-72 %) of the patients were
      transfused. Most had pancreatic ductal adenocarcinoma (69.5 %), while others had
      ampullary carcinoma (15.0 %), cholangiocarcinoma (7.4 %), or exocrine tumors of
      pancreas (8.1 %). Most (91.1 %) underwent pancreaticoduodenectomy, while the
      remaining patients underwent a total or distal pancreatectomy. The 5-year overall
      survival for all patients ranged from 0 to 65 %. Thirteen and nine of 19 studies
      reported a detrimental effect of PBT on survival on univariable and multivariable
      analysis, respectively. Overall, PBT was associated with shorter overall survival
      (pooled odds ratio 2.43, 95 % confidence interval 1.90-3.10); this finding was
      reproduced in sensitivity analysis. CONCLUSIONS: Patients receiving PBT had
      significantly lower 5-year survival after curative-intent pancreatic surgery.
      Further research should focus on implementing guidelines for and discerning
      factors associated with the poor outcomes after PBT.

PMID- 26293838
TI  - Genetic alterations in uterine fibroids - a new direction for pharmacological
      intervention?
AB  - INTRODUCTION: Though uterine leiomyomas (UL) (syn.: fibroids) are by far the most
      frequent human symptomatic tumors their pathogenesis still remains to be
      elucidated. From the detection of microscopically visible alterations of
      chromosomal structure and molecular cytogenetic analyses, as well as from
      transcriptome and genome analyses, a picture of a heterogeneous group of benign
      clonal smooth muscle neoplasms emerges that, for clinical as well as histological
      reasons, have been summarized under the headline 'UL'. AREAS COVERED: In this
      review, the authors address the background of genetic alterations identified in
      UL as well their possible clinical significance. EXPERT OPINION: Of the emerging
      genetic subgroups of UL those characterized by chromosomal alterations targeting
      high mobility group protein AT-hook 2 gene (10 - 20%) and those with point
      mutations of mediator subcomplex 12 (60 - 70%) predominate. Mechanistic models as
      to how these changes molecularly contribute to tumor development are lagging far
      behind their identification. Nevertheless, the different sizes of both types of
      myomas, their different tendency to occur as single or multiple tumors, and even
      a different probability to undergo malignant transformation suggest that in the
      future the clinical management of patients with fibroids will benefit from
      distinguishing between these latter as well as other more rare subgroups.

PMID- 26293839
TI  - Novel Equations for Estimating Lean Body Mass in Peritoneal Dialysis Patients.
AB  - ? OBJECTIVES: To develop and validate equations for estimating lean body mass
      (LBM) in peritoneal dialysis (PD) patients. ? METHODS: Two equations for
      estimating LBM, one based on mid-arm muscle circumference (MAMC) and hand grip
      strength (HGS), i.e., LBM-M-H, and the other based on HGS, i.e., LBM-H, were
      developed and validated with LBM obtained by dual-energy X-ray absorptiometry
      (DEXA). The developed equations were compared to LBM estimated from creatinine
      kinetics (LBM-CK) and anthropometry (LBM-A) in terms of bias, precision, and
      accuracy. The prognostic values of LBM estimated from the equations in all-cause
      mortality risk were assessed. ? RESULTS: The developed equations incorporated
      gender, height, weight, and dialysis duration. Compared to LBM-DEXA, the bias of
      the developed equations was lower than that of LBM-CK and LBM-A. Additionally,
      LBM-M-H and LBM-H had better accuracy and precision. The prognostic values of LBM
      in all-cause mortality risk based on LBM-M-H, LBM-H, LBM-CK, and LBM-A were
      similar. ? CONCLUSIONS: Lean body mass estimated by the new equations based on
      MAMC and HGS was correlated with LBM obtained by DEXA and may serve as practical
      surrogate markers of LBM in PD patients.

PMID- 26293840
TI  - Biomarkers Associated with Vascular Calcification in Peritoneal Dialysis.
AB  - ? BACKGROUND: Vascular calcification is strongly associated with cardiovascular
      disease and mortality. However, some factors related to vascular calcification in
      patients with end-stage renal disease receiving peritoneal dialysis (PD) remain
      unknown. This study aimed to evaluate the associations of osteoprotegerin (OPG),
      osteopontin (OPN), osteocalcin (OCN), fibroblast growth factor 23 (FGF-23),
      magnesium, and phosphate clearance with vascular calcification in PD subjects,
      assessed by plain radiographs. ? METHODS: Simple vascular calcification scores
      (SVCS) obtained from plain X-rays of the pelvis and hands, and the Kauppila Index
      (KI) from lateral lumbar X-rays were assessed in 76 adults receiving PD for >= 6
      months (43 women, median age 39 years, median time on PD 1.4 years). Levels of
      OPG, OPN, OCN, and FGF-23 were determined by luminometry. ? RESULTS: Serum OPG
      levels were higher in subjects with vascular calcification (n = 22 with SVCS > 3;
      n = 19 with KI > 7) compared with those with less calcification (p < 0.001).
      Spearman's correlation coefficients between OPG and SVCS and KI were r = 0.49 and
      r = 0.51, respectively (both p < 0.001). Subjects with vascular calcification had
      significantly lower renal phosphate clearance. Multiple regression analysis
      showed that vascular calcification assessed by SVCS was associated with age (r =
      0.2, p = 0.042), diabetes mellitus (r = 2.4, p < 0.001), body mass index (BMI) (r
      = 0.09, p = 0.037), and OPG (r = 0.22, p = 0.001). Vascular calcification
      assessed by KI was associated with age (r = 0.16, p < 0.001), time on PD (r =
      0.54, p = 0.001) and OPG (r = 0.08, p = 0.04). Osteocalcin, OPN, FGF-23, and
      magnesium were not associated with vascular calcification. ? CONCLUSIONS: Higher
      levels of OPG were consistently associated with vascular calcification in
      subjects on PD.

PMID- 26293841
TI  - Volume-Based Peritoneal Dialysis Prescription Guide to Achieve Adequacy Targets.
AB  - ? BACKGROUND: The use of automated and continuous ambulatory peritoneal dialysis
      (APD and CAPD) prescriptions (Rxs) to achieve adequate uremic toxin and fluid
      removal targets is important for attaining optimal patient outcomes. One approach
      for predicting such Rxs is the use of kinetic modeling. ? METHODS: Demographic
      data and peritoneal membrane characteristics derived from a peritoneal
      equilibration test (PET) were available from 1,005 patients in North American
      centers who participated in a national adequacy initiative in 1999. Twelve
      patient subgroups were identified according to peritoneal membrane transport type
      and tertiles of total body water, assumed equal to urea distribution volume
      (Vurea). Each patient was then modeled using PD Adequest 2.0 to be treated by 12
      CAPD and 34 APD Rxs using both glucose and icodextrin solutions to achieve
      adequacy targets of weekly urea Kt/V of 1.7 and 1 L of daily ultrafiltration
      (UF). Residual kidney function (RKF) was assumed to be 0, 2, 4, and 6 mL/min.
      Feasible peritoneal dialysis (PD) Rxs were identified where: 1) the 95%
      confidence limit achieved the goal of meeting the targets for urea Kt/V, daily
      UF, and both in 85%, 75%, and 70% of patients, respectively; 2) average PD
      solution dextrose concentration was < 2.5%; and 3) the number of daytime
      exchanges was minimized. ? RESULTS: Feasible PD Rxs were similar when RKF was >=
      2 mL/min, allowing condensed recommendations based on RKF >= 2 mL/min or < 2
      mL/min. Individuals with lower or slower membrane transport required relatively
      greater 24-h solution volumes to achieve adequacy targets when RKF fell below 2
      mL/min. With increasing Vurea, there was disproportionately greater dependence on
      RKF to achieve targets. While multiple Rxs achieving urea Kt/V and daily UF goals
      were identified for all membrane transport types, use of icodextrin in the long
      dwell reduced the need for a midday exchange in APD, glucose exposure, required
      fill and 24-h dwell volumes, irrespective of RKF and Vurea. While these benefits
      were most notable in high and high-average transporters, similar results were
      also seen in low and low-average transporters. ? CONCLUSIONS: Kinetic modeling
      identified multiple APD and CAPD Rxs that achieved adequate uremic solute and
      fluid removal for patients, irrespective of RKF and Vurea. Use of icodextrin
      rather than glucose in the long dwell reduced the complexity of the PD regimen,
      total glucose exposure, and 24-h total treatment solution volumes. Irrespective
      of modeling, adequacy of any PD prescription should be based upon individual
      clinical evaluation both for volume and solute removal.

PMID- 26293842
TI  - Reverse Epidemiology of Blood Pressure in Peritoneal Dialysis Associated with
      Dynamic Deterioration of Left Ventricular Function.
AB  - ? BACKGROUND: Reverse epidemiology of blood pressure (BP) in end-stage kidney
      disease (ESKD) is manifested as higher mortality at lower blood pressure. We
      hypothesize that this phenomenon is partially mediated by deterioration of
      cardiac structure and function. ? METHODS: Seventy-seven prevalent ESKD patients
      starting renal replacement therapy on peritoneal dialysis (PD) from 2007 to 2012
      were evaluated for the primary outcome of all-cause mortality. Longitudinal data
      were obtained from 1,930 patient-encounters including monthly clinic BP and
      serial echocardiograms. Generalized linear mixed models using data from the last
      observation moving backward, and time-to-event analysis using time-varying Cox
      survival models to estimate mortality risk at different blood pressure categories
      were applied. ? RESULTS: There were 39 males (50.6%). Mean age was 51 years
      (standard deviation [SD] = 15). During follow-up, 20 patients (25%) died. As
      compared to systolic blood pressure (SBP) of 140-159 mmHg, unadjusted risk of
      mortality was 7.3 (95% confidence interval [CI]: 1.5-35.7, p = 0.008) at level <
      120 mmHg. Systolic BP trended down to an average of 117 mmHg prior to death in
      non-survivors as compared to 141 mmHg in survivors (p < 0.05). In non-survivors,
      percentage with concentric left ventricular hypertrophy (LVH) decreased by 20% at
      the expense of a 20% reciprocal increase in eccentric hypertrophy associated with
      a 30% increase in percentage with low ejection fraction (EF) (< 50%). After
      adjusting for EF, risk of mortality at SBP < 120 mmHg attenuated to 3.4 (95% CI:
      0.7-17.7, p = 0.14). ? CONCLUSION: We conclude that higher mortality associated
      with lower BP may be mediated in part by worsening heart function in ESKD
      patients receiving PD.

PMID- 26293843
TI  - Non-malignant T-cells lacking multiple pan-T markers can be found in lymph nodes.
AB  - In order to observe and ascertain the properties of a sub-group of T cells in the
      lymph node (LN) from seven patients who did not suffer from T cell
      lymphoproliferative disorders (T-LPDs), the expression levels of several pan-T
      markers were evaluated by multiparameter flow cytometry (FC) and the clonality of
      these T-cells was evaluated by both FC analysis and PCR assessment. It turned out
      that multiple pan-T-cell markers such as CD2, CD5 and CD7 were found to be lost
      in these T cells. The majority of them were positive for TCRalphabeta, only a
      minority of them being positive for TCRgammadelta. A subset of these T-cells were
      positive for CD4 or CD8 or dual-negative for CD4 and CD8. Oligoclonality was
      detected in one case by FC, while clonal TCR rearrangement was detected in three
      cases. Absence of multiple pan-T-cell markers could be found in benign T cells in
      LNs.

PMID- 26293844
TI  - Inter- and intra-observer variability in the classification of extracapsular
      extension in p16 positive oropharyngeal squamous cell carcinoma nodal metastases.
AB  - OBJECTIVE: Discern inter- and intra-observer variability in the classification of
      extracapsular extension (ECE) in p16+ oropharyngeal (OP) SCC comparing
      pathologists' own criteria versus those of a well-defined classification system.
      METHODS: Five pathologists reviewed 50 digitally scanned nodal metastasis slides
      in three Rounds. Round One was by their own criteria as ECE present or absent,
      and Rounds Two and Three were with a defined ECE system: Grade 0 (no ECE), 0c (no
      ECE - thick capsule; no infiltration), 1 (ECE - cells beyond capsule), and 2
      (soft tissue metastasis - cells in soft tissue without residual node). Round
      Three assessed intra-observer variability after an 8 month washout period.
      RESULTS: In Round One, all five agreed on only 48% of cases (n=24). Fleiss's
      Kappa value was 0.508 (95% CI: 0.357-0.644). For Rounds Two and Three, Grades 0
      and 0c and Grades 1 and 2 were separately grouped as ECE absent or present. In
      Round Two, all five agreed on 68% of cases (n=34). Fleiss' Kappa was 0.635 (95%
      CI: 0.472-0.783), indicating statistically significantly better agreement. In
      Round Three, all five agreed on 64% of cases (n=32) giving a Fleiss's Kappa of
      0.639. Pathologists agreed with their prior reads in approximately 90% of cases
      (average n=45.4, range n=42-49), an average intra-observer Cohen's Kappa of 0.8
      (range: 0.68-0.95). Inter- and intra-observer variability rates for
      classification of soft tissue metastasis (ECE2) were substantially worse.
      CONCLUSION: There is substantial inter-, and modest intra-, observer variability
      among head and neck pathologists for ECE in p16+ OPSCC, which is modestly
      improved by a defined system.

PMID- 26293845
TI  - Impact of the new IADPSG gestational diabetes diagnostic criteria on pregnancy
      outcomes in Western Australia.
AB  - BACKGROUND: There is debate as to the most appropriate diagnostic criteria to
      diagnose gestational diabetes mellitus (GDM). The proposed International
      Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria have
      recently been endorsed by various bodies, but there remains no national
      consensus. AIM: To assess the perinatal outcomes of women with GDM classified
      according to the 1998 Australasian Diabetes in Pregnancy Society (ADIPS) criteria
      compared to those with GDM by the IADPSG criteria. MATERIALS AND METHODS: Results
      of glucose tolerance tests performed between January 2011 and January 2014 were
      linked with the perinatal data of those who delivered singleton fetuses after 24
      weeks' gestation. Analysed data included birthweight, gestational age at birth,
      macrosomia, mode of delivery, perinatal mortality, nursery admission, maternal
      body mass index, and gestational weight gain. RESULTS: Of 3571 women, 466 (13%)
      and 559 (16%) met the criteria for the 1998 ADIPS and IADPSG criteria for GDM,
      respectively. Those with GDM according to the IADPSG criteria only (6%) were more
      obese (95% CI 2.3-4.8 kg/m(2) ), delivered neonates on average 106 g heavier (95%
      CI 19-193 g) and had more fetal macrosomia (18% vs 11%, P = 0.002) than those
      with normal glucose tolerance. CONCLUSIONS: The IADPSG criteria for GDM
      identified a group of women at previously unrecognised increased risk of adverse
      perinatal outcomes. Adopting the IADPSG criteria would increase the number of
      women diagnosed with GDM by 20%; however, the improvements in perinatal
      morbidity, in addition to potential long-term benefits, may justify the increase
      in healthcare workload.

PMID- 26293847
TI  - Informatics Systems and Tools to Facilitate Patient-centered Care Coordination.
AB  - INTRODUCTION: There is a growing international focus on patient- centered care. A
      model designed to facilitate this type of care in the primary care setting is the
      patient-centered medical home. This model of care strives to be patient-focused,
      comprehensive, team-based, coordinated, accessible, and focused on quality and
      safety of care. OBJECTIVE: The objective of this paper is to identify the current
      status and future trends of patient-centered care and the role of informatics
      systems and tools in facilitating this model of care. METHODS: In this paper we
      review recent scientific literature of the past four years to identify trends and
      state of current evidence when it comes to patient-centered care overall, and
      more specifically medical homes. RESULTS: There are several studies that indicate
      growth and development in seven informatics areas within patient-centered care,
      namely clinical decision support, registries, team care, care transitions,
      personal health records, telehealth, and measurement. In some cases we are still
      lacking large randomized clinical trials and the evidence base is not always
      solid, but findings strongly indicate the potential of informatics to support
      patient-centered care. CONCLUSION: Current evidence indicates that advancements
      have been made in implementing and evaluating patient-centered care models.
      Technical, legal, and practical challenges still remain. Further examination of
      the impact of patient-centered informatics tools and systems on clinical outcomes
      is needed.

PMID- 26293848
TI  - Health Information Technology Coordination to Support Patient-centered Care
      Coordination.
AB  - OBJECTIVE: To select papers published in 2014, illustrating how information
      technology can contribute to and improve patient-centered care coordination.
      METHOD: The two section editors performed a literature review from Medline and
      Web of Science to select a list of candidate best papers on the use of
      information technology for patient-centered care coordination. These papers were
      peer-reviewed by external reviewers and three of them were selected as "best
      papers". RESULTS: The first selected paper reports a qualitative study exploring
      the gap between current practices of care coordination in various settings and
      idealized longitudinal care plans. The second selected paper illustrates several
      unintended consequences of HIT designed to improve care coordination. The third
      selected paper shows that advanced analytic techniques in medical informatics can
      be instrumental in studying patient-centered care coordination. CONCLUSIONS: The
      realization of true patient-centered care coordination is dependent upon a number
      of factors. Standardization of clinical documentation and HIT interoperability
      across organization and settings is a critical prerequisite for HIT to support
      patient-centered care coordination. Enabling patient involvement is an efficient
      means for goal setting and health information sharing. Additionally, unintended
      consequences of HIT tools (both positive and negative) must be measured and taken
      into account for quality improvement.

PMID- 26293846
TI  - Instigation of endothelial Nlrp3 inflammasome by adipokine visfatin promotes
      inter-endothelial junction disruption: role of HMGB1.
AB  - Recent studies have indicated that the inflammasome plays a critical role in the
      pathogenesis of vascular diseases. However, the pathological relevance of this
      inflammasome activation, particularly in vascular cells, remains largely unknown.
      Here, we investigated the role of endothelial (Nucleotide-binding Oligomerization
      Domain) NOD-like receptor family pyrin domain containing three (Nlrp3)
      inflammasomes in modulating inter-endothelial junction proteins, which are
      associated with endothelial barrier dysfunction, an early onset of obesity
      associated endothelial injury. Our findings demonstrate that the activation of
      Nlrp3 inflammasome by visfatin markedly decreased the expression of inter
      endothelial junction proteins including tight junction proteins ZO-1, ZO-2 and
      occludin, and adherens junction protein VE-cadherin in cultured mouse vascular
      endothelial (VE) cell monolayers. Such visfatin-induced down-regulation of
      junction proteins in endothelial cells was attributed to high mobility group box
      protein 1 (HMGB1) release derived from endothelial inflammasome-dependent caspase
      1 activity. Similarly, in the coronary arteries of wild-type mice, high-fat diet
      (HFD) treatment caused a down-regulation of inter-endothelial junction proteins
      ZO-1, ZO-2, occludin and VE-cadherin, which was accompanied with enhanced
      inflammasome activation and HMGB1 expression in the endothelium as well as
      transmigration of CD43(+) T cells into the coronary arterial wall. In contrast,
      all these HFD-induced alterations in coronary arteries were prevented in mice
      with Nlrp3 gene deletion. Taken together, these data strongly suggest that the
      activation of endothelial Nlrp3 inflammasomes as a result of the increased
      actions of injurious adipokines such as visfatin produces HMGB1, which act in
      paracrine or autocrine fashion to disrupt inter-endothelial junctions and
      increase paracellular permeability of the endothelium contributing to the early
      onset of endothelial injury during metabolic disorders such as obesity or high
      fat/cholesterol diet. 

PMID- 26293850
TI  - A 2015 Medical Informatics Perspective on Health and Clinical Management: Will
      Cloud and Prioritization Solutions Be the Future of Health Data Management?
AB  - OBJECTIVES: Summarize current excellent research and trends in the field of
      Health and Clinical management. METHODS: Synopsis of the articles selected for
      the IMIA Yearbook 2015 RESULTS: Three papers from international peer-reviewed
      journals have been selected for the Health and Clinical Management section.
      CONCLUSION: Telemedicine is still very active in Health and clinical management,
      but the new tendencies on which we focus this year were firstly the introduction
      of cloud for health data management, with some specific security problems, and
      secondly an emerging expectation of prioritization tools in health care
      Management.

PMID- 26293849
TI  - Health Informatics via Machine Learning for the Clinical Management of Patients.
AB  - OBJECTIVES: To review how health informatics systems based on machine learning
      methods have impacted the clinical management of patients, by affecting clinical
      practice. METHODS: We reviewed literature from 2010-2015 from databases such as
      Pubmed, IEEE xplore, and INSPEC, in which methods based on machine learning are
      likely to be reported. We bring together a broad body of literature, aiming to
      identify those leading examples of health informatics that have advanced the
      methodology of machine learning. While individual methods may have further
      examples that might be added, we have chosen some of the most representative,
      informative exemplars in each case. RESULTS: Our survey highlights that, while
      much research is taking place in this high-profile field, examples of those that
      affect the clinical management of patients are seldom found. We show that
      substantial progress is being made in terms of methodology, often by data
      scientists working in close collaboration with clinical groups. CONCLUSIONS:
      Health informatics systems based on machine learning are in their infancy and the
      translation of such systems into clinical management has yet to be performed at
      scale.

PMID- 26293851
TI  - Mobile Applications for Patient-centered Care Coordination: A Review of Human
      Factors Methods Applied to their Design, Development, and Evaluation.
AB  - OBJECTIVES: To examine if human factors methods were applied in the design,
      development, and evaluation of mobile applications developed to facilitate
      aspects of patient-centered care coordination. METHODS: We searched MEDLINE and
      EMBASE (2013-2014) for studies describing the design or the evaluation of a
      mobile health application that aimed to support patients' active involvement in
      the coordination of their care. RESULTS: 34 papers met the inclusion criteria.
      Applications ranged from tools that supported self-management of specific
      conditions (e.g. asthma) to tools that provided coaching or education. Twelve of
      the 15 papers describing the design or development of an app reported the use of
      a human factors approach. The most frequently used methods were interviews and
      surveys, which often included an exploration of participants' current use of
      information technology. Sixteen papers described the evaluation of a patient
      application in practice. All of them adopted a human factors approach, typically
      an examination of the use of app features and/or surveys or interviews which
      enquired about patients' views of the effects of using the app on their behaviors
      (e.g. medication adherence), knowledge, and relationships with healthcare
      providers. No study in our review assessed the impact of mobile applications on
      health outcomes. CONCLUSION: The potential of mobile health applications to
      assist patients to more actively engage in the management of their care has
      resulted in a large number of applications being developed. Our review showed
      that human factors approaches are nearly always adopted to some extent in the
      design, development, and evaluation of mobile applications.

PMID- 26293852
TI  - Human Factors and Ergonomics in the Design of Health Information Technology:
      Trends and Progress in 2014.
AB  - OBJECTIVE: To summarize significant contributions to the research on human
      factors and organizational issues in medical informatics. METHODS: An extensive
      search using PubMed/Medline and Web of Science(r) was conducted to identify the
      scientific contributions, published in 2014, to human factors and organizational
      issues in medical informatics, with a focus on health information technology
      (HIT) usability. The selection process comprised three steps: (i) 15 candidate
      best papers were selected by the two section editors, (ii) external reviewers
      from a pool of international experts reviewed each candidate best paper, and
      (iii) the final selection of three best papers was made by the editorial board of
      the IMIA Yearbook. RESULTS: Noteworthy papers published in 2014 describe an
      efficient, easy to implement, and useful process for detecting and mitigating
      human factors and ergonomics (HFE) issues of HIT. They contribute to promote the
      HFE approach with interventions based on rigorous and well-conducted methods when
      designing and implementing HIT. CONCLUSION: The application of HFE in the design
      and implementation of HIT remains limited, and the impact of incorporating HFE
      principles on patient safety is understudied. Future works should be conducted to
      advance this field of research, so that the safety and quality of patient care
      are not compromised by the increasing adoption of HIT.

PMID- 26293853
TI  - A Systematic Investigation on Barriers and Critical Success Factors for Clinical
      Information Systems in Integrated Care Settings.
AB  - OBJECTIVES: Clinical Information Systems (CIS) have ever since the introduction
      of information technology in healthcare played an important role to support
      healthcare professionals and the process of treatment. With the rise of the
      concept of integrated care organizational borders, the sole focus on data
      aggregation or healthcare professionals as users disappear more and more. The
      manuscript discusses the concept of CISs and investigates critical success
      factors for CISs in the context of integrated care and in the course of time.
      METHODS: In order to identify critical success factors and barriers for CISs a
      systematic literature review was conducted based on the results from PubMed and
      Cochrane, using MaxQDA. Search results were thereby limited to reviews or meta
      analysis. RESULTS: We have found 1919 references of which 40 met the inclusion
      criteria. The analysis of the manuscripts resulted in a comprehensive list of
      success factors and barriers related to CISs in integrated care settings. Most
      barriers were user-related whereas for the success factors an even distribution
      of organizational, technical and user-related factors was observed. The vast
      majority of publications was focused on healthcare professionals. CONCLUSION: It
      is important to incorporate experiences made/ collected over time, as the
      problems encountered seem to remain almost unvaried. In order to support further
      systematic investigations on the topic it is necessary to rethink existing
      concepts and definitions to realign them with the ideas of integrated care.

PMID- 26293854
TI  - Findings from the Clinical Information Systems Perspective.
AB  - OBJECTIVE: To summarize recent research and to propose a selection of best papers
      published in 2014 in the field of Clinical Information Systems (CIS). METHOD: A
      query with search terms from the Medical Subject Headings (MeSH) catalog as well
      as additional free text search terms was designed to identify relevant
      publications in the field of clinical information systems from PubMed and Web of
      Science(r). The retrieved articles were then categorized in a multi-pass review
      carried out separately by the section editors. The final selection of 15
      candidate papers was then peerreviewed by Yearbook editors and external
      reviewers. Based on the review results the four best papers were then selected at
      the best papers selection meeting with the IMIA Yearbook editorial board.
      RESULTS: The query was carried out in mid-January 2015, yielding a combined
      result set of 1525 articles which were published in 722 different journals. Among
      these articles two main thematic sections were identified: i) Interoperability
      from a syntactical and semantic point of view as well as from a longterm
      preservation and organizational/legal point of view and ii) secondary use of
      existing health data in all its shades. Here, patient safety was a major scope of
      application. CONCLUSIONS: CIS have become mature over the last years. The focus
      has now moved beyond data acquisition for just supporting the local care
      workflows. Actual research efforts in the CIS domain comprise the breakdown of
      information silos, the reduction of barriers between different systems of
      different care providers and secondary use of accumulated health data for
      multiple purposes.

PMID- 26293855
TI  - Physiological Signal Processing for Individualized Anti-nociception Management
      During General Anesthesia: a Review.
AB  - OBJECTIVE: The aim of this paper is to review existing technologies for the
      nociception / anti-nociception balance evaluation during surgery under general
      anesthesia. METHODS: General anesthesia combines the use of analgesic, hypnotic
      and muscle-relaxant drugs in order to obtain a correct level of patient non
      responsiveness during surgery. During the last decade, great efforts have been
      deployed in order to find adequate ways to measure how anesthetic drugs affect a
      patient's response to surgical nociception. Nowadays, though some monitoring
      devices allow obtaining information about hypnosis and muscle relaxation, no gold
      standard exists for the nociception / anti-nociception balance evaluation.
      Articles from the PubMed literature search engine were reviewed. As this paper
      focused on surgery under general anesthesia, articles about nociception
      monitoring on conscious patients, in post-anesthesia care unit or in intensive
      care unit were not considered. RESULTS: In this article, we present a review of
      existing technologies for the nociception / anti-nociception balance evaluation,
      which is based in all cases on the analysis of the autonomous nervous system
      activity. Presented systems, based on sensors and physiological signals
      processing algorithms, allow studying the patients' reaction regarding anesthesia
      and surgery. CONCLUSION: Some technological solutions for nociception /
      antinociception balance monitoring were described. Though presented devices could
      constitute efficient solutions for individualized anti-nociception management
      during general anesthesia, this review of current literature emphasizes the fact
      that the choice to use one or the other mainly relies on the clinical context and
      the general purpose of the monitoring.

PMID- 26293856
TI  - How Sensor, Signal, and Imaging Informatics May Impact Patient Centered Care and
      Care Coordination.
AB  - OBJECTIVE: This synopsis presents a selection for the IMIA (International Medical
      Informatics Association) Yearbook 2015 of excellent research in the broad field
      of Sensor, Signal, and Imaging Informatics published in the year 2014, with a
      focus on patient centered care coordination. METHODS: The two section editors
      performed a systematic initial selection and a double blind peer review process
      to select a list of candidate best papers in the domain published in 2014, from
      the PubMed and Web of Science databases. A set of MeSH keywords provided by
      experts was used. This selection was peer-reviewed by external reviewers.
      RESULTS: The review process highlighted articles illustrating two current trends
      related to care coordination and patient centered care: the enhanced capacity to
      predict the evolution of a disease based on patient-specific information can
      impact care coordination; similarly, better perception of the patient and his
      treatment could lead to enhanced personalized care with a potential impact on
      care coordination. CONCLUSIONS: This review shows the multiplicity of angles from
      which the question of patient-centered care can be addressed, with consequences
      on care coordination that will need to be confirmed and demonstrated in the
      future.

PMID- 26293858
TI  - Computerized Clinical Decision Support: Contributions from 2014.
AB  - OBJECTIVE: To summarize recent research and propose a selection of best papers
      published in 2014 in the field of computerized clinical decision support for the
      Decision Support section of the IMIA yearbook. METHOD: A literature review was
      performed by searching two bibliographic databases for papers related to clinical
      decision support systems (CDSSs) and computerized provider order entry systems in
      order to select a list of candidate best papers to be then peer-reviewed by
      external reviewers. A consensus meeting between the two section editors and the
      editorial team was finally organized to conclude on the selection of best papers.
      RESULTS: Among the 1,254 returned papers published in 2014, the full review
      process selected four best papers. The first one is an experimental contribution
      to a better understanding of unintended uses of CDSSs. The second paper describes
      the effective use of previously collected data to tailor and adapt a CDSS. The
      third paper presents an innovative application that uses pharmacogenomic
      information to support personalized medicine. The fourth paper reports on the
      long-term effect of the routine use of a CDSS for antibiotic therapy.
      CONCLUSIONS: As health information technologies spread more and more
      meaningfully, CDSSs are improving to answer users' needs more accurately. The
      exploitation of previously collected data and the use of genomic data for
      decision support has started to materialize. However, more work is still needed
      to address issues related to the correct usage of such technologies, and to
      assess their effective impact in the long term.

PMID- 26293859
TI  - Management of Dynamic Biomedical Terminologies: Current Status and Future
      Challenges.
AB  - OBJECTIVES: Controlled terminologies and their dependent artefacts provide a
      consensual understanding of a domain while reducing ambiguities and enabling
      reasoning. However, the evolution of a domain's knowledge directly impacts these
      terminologies and generates inconsistencies in the underlying biomedical
      information systems. In this article, we review existing work addressing the
      dynamic aspect of terminologies as well as their effects on mappings and semantic
      annotations. METHODS: We investigate approaches related to the identification,
      characterization and propagation of changes in terminologies, mappings and
      semantic annotations including techniques to update their content. RESULTS AND
      CONCLUSION: Based on the explored issues and existing methods, we outline open
      research challenges requiring investigation in the near future.

PMID- 26293860
TI  - Knowledge Representation and Management. From Ontology to Annotation. Findings
      from the Yearbook 2015 Section on Knowledge Representation and Management.
AB  - OBJECTIVE: To summarize the best papers in the field of Knowledge Representation
      and Management (KRM). METHODS: A comprehensive review of medical informatics
      literature was performed to select some of the most interesting papers of KRM
      published in 2014. RESULTS: Four articles were selected, two focused on
      annotation and information retrieval using an ontology. The two others focused
      mainly on ontologies, one dealing with the usage of a temporal ontology in order
      to analyze the content of narrative document, one describing a methodology for
      building multilingual ontologies. CONCLUSION: Semantic models began to show their
      efficiency, coupled with annotation tools.

PMID- 26293857
TI  - Personalization and Patient Involvement in Decision Support Systems: Current
      Trends.
AB  - OBJECTIVES: This survey aims at highlighting the latest trends (2012-2014) on the
      development, use, and evaluation of Information and Communication Technologies
      (ICT) based decision support systems (DSSs) in medicine, with a particular focus
      on patient-centered and personalized care. METHODS: We considered papers
      published on scientific journals, by querying PubMed and Web of ScienceTM.
      Included studies focused on the implementation or evaluation of ICT-based tools
      used in clinical practice. A separate search was performed on computerized
      physician order entry systems (CPOEs), since they are increasingly embedding
      patient-tailored decision support. RESULTS: We found 73 papers on DSSs (53 on
      specific ICT tools) and 72 papers on CPOEs. Although decision support through the
      delivery of recommendations is frequent (28/53 papers), our review highlighted
      also DSSs only based on efficient information presentation (25/53). Patient
      participation in making decisions is still limited (9/53), and mostly focused on
      risk communication. The most represented medical area is cancer (12%). Policy
      makers are beginning to be included among stakeholders (6/73), but integration
      with hospital information systems is still low. Concerning knowledge
      representation/management issues, we identified a trend towards building
      inference engines on top of standard data models. Most of the tools (57%)
      underwent a formal assessment study, even if half of them aimed at evaluating
      usability and not effectiveness. CONCLUSIONS: Overall, we have noticed
      interesting evolutions of medical DSSs to improve communication with the patient,
      consider the economic and organizational impact, and use standard models for
      knowledge representation. However, systems focusing on patient-centered care
      still do not seem to be available at large.

PMID- 26293861
TI  - Ethical Issues of Social Media Usage in Healthcare.
AB  - OBJECTIVE: Social media, web and mobile technologies are increasingly used in
      healthcare and directly support patientcentered care. Patients benefit from
      disease self-management tools, contact to others, and closer monitoring.
      Researchers study drug efficiency, or recruit patients for clinical studies via
      these technologies. However, low communication barriers in socialmedia, limited
      privacy and security issues lead to problems from an ethical perspective. This
      paper summarizes the ethical issues to be considered when social media is
      exploited in healthcare contexts. METHODS: Starting from our experiences in
      social-media research, we collected ethical issues for selected social-media use
      cases in the context of patient-centered care. Results were enriched by
      collecting and analyzing relevant literature and were discussed and interpreted
      by members of the IMIA Social Media Working Group. RESULTS: Most relevant issues
      in social-media applications are confidence and privacy that need to be carefully
      preserved. The patient-physician relationship can suffer from the new information
      gain on both sides since private information of both healthcare provider and
      consumer may be accessible through the Internet. Physicians need to ensure they
      keep the borders between private and professional intact. Beyond, preserving
      patient anonymity when citing Internet content is crucial for research studies.
      CONCLUSION: Exploiting medical social-media in healthcare applications requires a
      careful reflection of roles and responsibilities. Availability of data and
      information can be useful in many settings, but the abuse of data needs to be
      prevented. Preserving privacy and confidentiality of online users is a main
      issue, as well as providing means for patients or Internet users to express
      concerns on data usage.

PMID- 26293862
TI  - Health Social Media and Patient-Centered Care: Buzz or Evidence? Findings from
      the Section "Education and Consumer Health Informatics" of the 2015 Edition of
      the IMIA Yearbook.
AB  - OBJECTIVE: To summarize the 2014 state of the art in the areas related to
      consumer health informatics and social media. METHODS: We conducted a systematic
      review of articles published in 2014 in PubMed with a predefined set of queries.
      We identified 439 articles relevant for the review. The two section editors
      independently screened those papers taking into account their relevance to the
      topics covered by the section. In a second step, they jointly selected the 20
      most representative papers as candidate best papers. Candidate best papers were
      then submitted for full review and scoring by external reviewers. Based on the
      scoring, section editors together with the IMIA Yearbook editorial board selected
      the four best papers published in 2014 in consumer health informatics. RESULTS:
      Helping patients acquire a healthier lifestyle is a crucial part of patient
      empowerment. In this line of work, new studies are exploring the efficacy of
      online health interventions for patient behavioral change. The special case of
      smoking cessation for consumers with low socio-economic status is particularly
      noticeable. Another study has explored how an online intervention can reduce the
      anxiety of women who experience an abnormal mammography. The team of
      PatientsLikeMe has studied how online support groups could play a role in the
      quality of life of organ transplant recipients. The patient perspective of online
      forums' users is also analyzed in the domain of anticoagulation therapy.
      CONCLUSIONS: Online health interventions, many of them using social media, have
      confirmed their potential to impact consumer behavioral change. However, there
      are still many methodological issues that need to be addressed in order to prove
      cost-effectiveness.

PMID- 26293863
TI  - From Molecules to Patients: The Clinical Applications of Translational
      Bioinformatics.
AB  - OBJECTIVE: In order to realize the promise of personalized medicine,
      Translational Bioinformatics (TBI) research will need to continue to address
      implementation issues across the clinical spectrum. In this review, we aim to
      evaluate the expanding field of TBI towards clinical applications, and define
      common themes and current gaps in order to motivate future research. METHODS:
      Here we present the state-of-the-art of clinical implementation of TBI-based
      tools and resources. Our thematic analyses of a targeted literature search of
      recent TBI-related articles ranged across topics in genomics, data management,
      hypothesis generation, molecular epidemiology, diagnostics, therapeutics and
      personalized medicine. RESULTS: Open areas of clinically-relevant TBI research
      identified in this review include developing data standards and best practices,
      publicly available resources, integrative systemslevel approaches, user-friendly
      tools for clinical support, cloud computing solutions, emerging technologies and
      means to address pressing legal, ethical and social issues. CONCLUSIONS: There is
      a need for further research bridging the gap from foundational TBI-based theories
      and methodologies to clinical implementation. We have organized the topic themes
      presented in this review into four conceptual foci - domain analyses, knowledge
      engineering, computational architectures and computation methods alongside three
      stages of knowledge development in order to orient future TBI efforts to
      accelerate the goals of personalized medicine.

PMID- 26293864
TI  - Bioinformatics Methods and Tools to Advance Clinical Care. Findings from the
      Yearbook 2015 Section on Bioinformatics and Translational Informatics.
AB  - OBJECTIVES: To summarize excellent current research in the field of
      Bioinformatics and Translational Informatics with application in the health
      domain and clinical care. METHOD: We provide a synopsis of the articles selected
      for the IMIA Yearbook 2015, from which we attempt to derive a synthetic overview
      of current and future activities in the field. As last year, a first step of
      selection was performed by querying MEDLINE with a list of MeSH descriptors
      completed by a list of terms adapted to the section. Each section editor has
      evaluated separately the set of 1,594 articles and the evaluation results were
      merged for retaining 15 articles for peer-review. RESULTS: The selection and
      evaluation process of this Yearbook's section on Bioinformatics and Translational
      Informatics yielded four excellent articles regarding data management and genome
      medicine that are mainly tool-based papers. In the first article, the authors
      present PPISURV a tool for uncovering the role of specific genes in cancer
      survival outcome. The second article describes the classifier PredictSNP which
      combines six performing tools for predicting disease-related mutations. In the
      third article, by presenting a high-coverage map of the human proteome using high
      resolution mass spectrometry, the authors highlight the need for using mass
      spectrometry to complement genome annotation. The fourth article is also related
      to patient survival and decision support. The authors present datamining methods
      of large-scale datasets of past transplants. The objective is to identify chances
      of survival. CONCLUSIONS: The current research activities still attest the
      continuous convergence of Bioinformatics and Medical Informatics, with a focus
      this year on dedicated tools and methods to advance clinical care. Indeed, there
      is a need for powerful tools for managing and interpreting complex, large-scale
      genomic and biological datasets, but also a need for user-friendly tools
      developed for the clinicians in their daily practice. All the recent research and
      development efforts contribute to the challenge of impacting clinically the
      obtained results towards a personalized medicine.

PMID- 26293865
TI  - Clinical Research Informatics: Recent Advances and Future Directions.
AB  - OBJECTIVES: To summarize significant developments in Clinical Research
      Informatics (CRI) over the past two years and discuss future directions. METHODS:
      Survey of advances, open problems and opportunities in this field based on
      exploration of current literature. RESULTS: Recent advances are structured
      according to three use cases of clinical research: Protocol feasibility, patient
      identification/ recruitment and clinical trial execution. DISCUSSION: CRI is an
      evolving, dynamic field of research. Global collaboration, open metadata, content
      standards with semantics and computable eligibility criteria are key success
      factors for future developments in CRI.

PMID- 26293866
TI  - Information Technology for Clinical, Translational and Comparative Effectiveness
      Research. Findings from the Yearbook 2015 Section on Clinical Research
      Informatics.
AB  - OBJECTIVES: To summarize excellent current research in the field of
      Bioinformatics and Translational Informatics with application in the health
      domain and clinical care. METHOD: We provide a synopsis of the articles selected
      for the IMIA Yearbook 2015, from which we attempt to derive a synthetic overview
      of current and future activities in the field. As last year, a first step of
      selection was performed by querying MEDLINE with a list of MeSH descriptors
      completed by a list of terms adapted to the section. Each section editor has
      evaluated separately the set of 1,594 articles and the evaluation results were
      merged for retaining 15 articles for peer-review. RESULTS: The selection and
      evaluation process of this Yearbook's section on Bioinformatics and Translational
      Informatics yielded four excellent articles regarding data management and genome
      medicine that are mainly tool-based papers. In the first article, the authors
      present PPISURV a tool for uncovering the role of specific genes in cancer
      survival outcome. The second article describes the classifier PredictSNP which
      combines six performing tools for predicting disease-related mutations. In the
      third article, by presenting a high-coverage map of the human proteome using high
      resolution mass spectrometry, the authors highlight the need for using mass
      spectrometry to complement genome annotation. The fourth article is also related
      to patient survival and decision support. The authors present datamining methods
      of large-scale datasets of past transplants. The objective is to identify chances
      of survival. CONCLUSIONS: The current research activities still attest the
      continuous convergence of Bioinformatics and Medical Informatics, with a focus
      this year on dedicated tools and methods to advance clinical care. Indeed, there
      is a need for powerful tools for managing and interpreting complex, large-scale
      genomic and biological datasets, but also a need for user-friendly tools
      developed for the clinicians in their daily practice. All the recent research and
      development efforts contribute to the challenge of impacting clinically the
      obtained results towards a personalized medicine.

PMID- 26293867
TI  - Recent Advances in Clinical Natural Language Processing in Support of Semantic
      Analysis.
AB  - OBJECTIVES: We present a review of recent advances in clinical Natural Language
      Processing (NLP), with a focus on semantic analysis and key subtasks that support
      such analysis. METHODS: We conducted a literature review of clinical NLP research
      from 2008 to 2014, emphasizing recent publications (2012-2014), based on PubMed
      and ACL proceedings as well as relevant referenced publications from the included
      papers. RESULTS: Significant articles published within this time-span were
      included and are discussed from the perspective of semantic analysis. Three key
      clinical NLP subtasks that enable such analysis were identified: 1) developing
      more efficient methods for corpus creation (annotation and de-identification), 2)
      generating building blocks for extracting meaning (morphological, syntactic, and
      semantic subtasks), and 3) leveraging NLP for clinical utility (NLP applications
      and infrastructure for clinical use cases). Finally, we provide a reflection upon
      most recent developments and potential areas of future NLP development and
      applications. CONCLUSIONS: There has been an increase of advances within key NLP
      subtasks that support semantic analysis. Performance of NLP semantic analysis is,
      in many cases, close to that of agreement between humans. The creation and
      release of corpora annotated with complex semantic information models has greatly
      supported the development of new tools and approaches. Research on non-English
      languages is continuously growing. NLP methods have sometimes been successfully
      employed in real-world clinical tasks. However, there is still a gap between the
      development of advanced resources and their utilization in clinical settings. A
      plethora of new clinical use cases are emerging due to established health care
      initiatives and additional patient-generated sources through the extensive use of
      social media and other devices.

PMID- 26293868
TI  - Clinical Natural Language Processing in 2014: Foundational Methods Supporting
      Efficient Healthcare.
AB  - OBJECTIVE: To summarize recent research and present a selection of the best
      papers published in 2014 in the field of clinical Natural Language Processing
      (NLP). METHOD: A systematic review of the literature was performed by the two
      section editors of the IMIA Yearbook NLP section by searching bibliographic
      databases with a focus on NLP efforts applied to clinical texts or aimed at a
      clinical outcome. A shortlist of candidate best papers was first selected by the
      section editors before being peer-reviewed by independent external reviewers.
      RESULTS: The clinical NLP best paper selection shows that the field is tackling
      text analysis methods of increasing depth. The full review process highlighted
      five papers addressing foundational methods in clinical NLP using clinically
      relevant texts from online forums or encyclopedias, clinical texts from
      Electronic Health Records, and included studies specifically aiming at a
      practical clinical outcome. The increased access to clinical data that was made
      possible with the recent progress of de-identification paved the way for the
      scientific community to address complex NLP problems such as word sense
      disambiguation, negation, temporal analysis and specific information nugget
      extraction. These advances in turn allowed for efficient application of NLP to
      clinical problems such as cancer patient triage. Another line of research
      investigates online clinically relevant texts and brings interesting insight on
      communication strategies to convey health-related information. CONCLUSIONS: The
      field of clinical NLP is thriving through the contributions of both NLP
      researchers and healthcare professionals interested in applying NLP techniques
      for concrete healthcare purposes. Clinical NLP is becoming mature for practical
      applications with a significant clinical impact.

PMID- 26293870
TI  - Modelling, Simulation and Social Network Data: What's New for Public Health and
      Epidemiology Informatics?

PMID- 26293869
TI  - Public Health and Epidemiology Informatics: Recent Research and Trends in the
      United States.
AB  - OBJECTIVES: To survey advances in public health and epidemiology informatics over
      the past three years. METHODS: We conducted a review of English-language research
      works conducted in the domain of public health informatics (PHI), and published
      in MEDLINE between January 2012 and December 2014, where information and
      communication technology (ICT) was a primary subject, or a main component of the
      study methodology. Selected articles were synthesized using a thematic analysis
      using the Essential Services of Public Health as a typology. RESULTS: Based on
      themes that emerged, we organized the advances into a model where applications
      that support the Essential Services are, in turn, supported by a socio-technical
      infrastructure that relies on government policies and ethical principles. That
      infrastructure, in turn, depends upon education and training of the public health
      workforce, development that creates novel or adapts existing infrastructure, and
      research that evaluates the success of the infrastructure. Finally, the
      persistence and growth of infrastructure depends on financial sustainability.
      CONCLUSIONS: Public health informatics is a field that is growing in breadth,
      depth, and complexity. Several Essential Services have benefited from
      informatics, notably, "Monitor Health," "Diagnose & Investigate," and "Evaluate."
      Yet many Essential Services still have not yet benefited from advances such as
      maturing electronic health record systems, interoperability amongst health
      information systems, analytics for population health management, use of social
      media among consumers, and educational certification in clinical informatics.
      There is much work to be done to further advance the science of PHI as well as
      its impact on public health practice.

PMID- 26293886
TI  - Congenital Chagas disease as an ecological model of interactions between
      Trypanosoma cruzi parasites, pregnant women, placenta and fetuses.
AB  - The aim of this paper is to discuss the main ecological interactions between the
      parasite Trypanosoma cruzi and its hosts, the mother and the fetus, leading to
      the transmission and development of congenital Chagas disease. One or several
      infecting strains of T. cruzi (with specific features) interact with: (i) the
      immune system of a pregnant woman whom responses depend on genetic and
      environmental factors, (ii) the placenta harboring its own defenses, and,
      finally, (iii) the fetal immune system displaying responses also susceptible to
      be modulated by maternal and environmental factors, as well as his own genetic
      background which is different from her mother. The severity of congenital Chagas
      disease depends on the magnitude of such final responses. The paper is mainly
      based on human data, but integrates also complementary observations obtained in
      experimental infections. It also focuses on important gaps in our knowledge of
      this congenital infection, such as the role of parasite diversity vs host genetic
      factors, as well as that of the maternal and placental microbiomes and the
      microbiome acquisition by infant in the control of infection. Investigations on
      these topics are needed in order to improve the programs aiming to diagnose,
      manage and control congenital Chagas disease. 

PMID- 26293885
TI  - The Architecture of the TIR Domain Signalosome in the Toll-like Receptor-4
      Signaling Pathway.
AB  - Activated Toll-like receptors (TLRs) cluster in lipid rafts and induce pro- and
      anti-tumor responses. The organization of the assembly is critical to the
      understanding of how these key receptors control major signaling pathways in the
      cell. Although several models for individual interactions were proposed, the
      entire TIR-domain signalosome architecture has not been worked out, possibly due
      to its complexity. We employ a powerful algorithm, crystal structures and
      experimental data to model the TLR4 and its cluster. The architecture that we
      obtain with 8 MyD88 molecules provides the structural basis for the MyD88
      templated myddosome helical assembly and receptor clustering; it also provides
      clues to pro- and anti-inflammatory signaling pathways branching at the
      signalosome level to Mal/MyD88 and TRAM/TRIF pro- and anti-inflammatory pathways.
      The assembly of MyD88 death domain (DD) with TRAF3 (anti-viral/anti-inflammatory)
      and TRAF6 (pro-inflammatory) suggest that TRAF3/TRAF6 binding sites on MyD88 DD
      partially overlap, as do IRAK4 and FADD. Significantly, the organization
      illuminates mechanisms of oncogenic mutations, demonstrates that almost all TLR4
      parallel pathways are competitive and clarifies decisions at pathway branching
      points. The architectures are compatible with the currently-available
      experimental data and provide compelling insights into signaling in cancer and
      inflammation pathways. 

PMID- 26293887
TI  - Cost-Effectiveness Modeling in Multiple Sclerosis: Playing Around with Non
      Healthcare Costs?

PMID- 26293888
TI  - Impact of Small Renal Ischemia in Hypertension Development: Renovascular
      Hypertension Caused by Small Branch Artery Stenosis.

PMID- 26293889
TI  - Central Somatosensory Networks Respond to a De Novo Innervated Penis: A Proof of
      Concept in Three Spina Bifida Patients.
AB  - INTRODUCTION: Spina bifida (SB) causes low spinal lesions, and patients often
      have absent genital sensation and a highly impaired sex life. TOMAX (TO MAX-imize
      sensation, sexuality and quality of life) is a surgical procedure whereby the
      penis is newly innervated using a sensory nerve originally targeting the inguinal
      area. Most TOMAX-treated SB patients initially experience penile stimulation as
      inguinal sensation, but eventually, the perception shifts to penis sensation with
      erotic feelings. The brain mechanisms mediating this perceptual shift, which are
      completely unknown, could hold relevance for understanding the brain's role in
      sexual development. AIM: The aim of this study was to study how a newly perceived
      penis would be mapped onto the brain after a lifelong disconnection. METHODS:
      Three TOMAX-treated SB patients participated in a functional magnetic resonance
      imagery experiment while glans penis, inguinal area, and index finger were
      stimulated with a paint brush. MAIN OUTCOME MEASURE: Brush stimulation-induced
      activation of the primary somatosensory cortex (SI) and functional connectivity
      between SI and remote cerebral regions. RESULTS: Stimulation of the re-innervated
      side of the glans penis and the intact contralateral inguinal area activated a
      very similar location on SI. Yet, connectivity analysis identified distinct SI
      functional networks. In all three subjects, the middle cingulate cortex (MCC) and
      the parietal operculum-insular cortex (OIC) were functionally connected to SI
      activity during glans penis stimulation, but not to SI activity induced by
      inguinal stimulation. CONCLUSIONS: Investigating central somatosensory network
      activity to a de novo innervated penis in SB patients is feasible and
      informative. The consistent involvement of MCC and OIC above and beyond the brain
      network expected on the basis of inguinal stimulation suggests that these areas
      mediate the novel penis sensation in these patients. The potential role of MCC
      and OIC in this process is discussed, along with recommendations for further
      research.

PMID- 26293891
TI  - Reservoir sediments: a sink or source of chemicals at the surface water
      groundwater interface.
AB  - This study delineates the physical, chemical, and biological effects resulting
      from anthropogenic and endogenic activities in a sensitive dammed reservoir
      situated in a semi-arid region. The reservoir is characterized by two major flow
      regimes: a wet fill hydrologic regime and a dry spill one. A seasonal sampling
      campaign was carried out over a period of 2 years (2011-2013) where water samples
      were collected across the water column and from piezometers just outside the
      perimeter of the reservoir. Similarly, sediments were collected from the
      corresponding areas beneath the water column. The water samples were analyzed for
      environmental isotopic ratios, elemental composition, and physical, biological
      and chemical parameters, whereas the sediment and algal samples were subjected to
      physical, mineralogical, spectroscopic, and microscopic analyses. This
      investigation indicated that the dam had resulted in the alteration of the
      biogeochemical cycle of nutrients as well as the degradation of the sediment and
      water quality. The hydrological and biogeochemical processes were found to induce
      vertical downward transport of chemicals towards the fine grained calcareous
      sediments during the fill mode, whereas the sediments acted as a source of a
      chemical flux upward through the water column and downward towards the
      groundwater during the spill mode. The geomorphological characteristics of the
      reservoir enhanced the strong hydrological connectivity between the surface water
      and the groundwater where the reservoir responded quickly to natural and
      anthropogenic changes in the upper watershed. The water and sediments in the
      sensitive spill mode were of poor quality and should receive more attention due
      to the potential hazard for the associated hydro-project and the sustainability
      of the agricultural soil in the long term. Thus, a safe water and sediment
      management plan should be implemented in order to improve the dam functionality
      and to safeguard the precious water resources.

PMID- 26293890
TI  - Atypical role of sprouty in p21 dependent inhibition of cell proliferation in
      colorectal cancer.
AB  - Sprouty (SPRY) appears to act as a tumor suppressor in cancer, whereas we
      reported that SPRY2 functions as a putative oncogene in colorectal cancer (CRC)
      [Oncogene, 2010, 29: 5241-5253]. In general, various studies established
      inhibition of cell proliferation by SPRY in cancer. The mechanisms by which SPRY
      regulates cell proliferation in CRC are investigated. We demonstrate, for the
      first time, suppression of SPRY2 augmented EGF-dependent oncogenic signaling,
      however, surprisingly decreased cell proliferation in colon cancer cells. Our
      data suggest that cell cycle inhibitor p21(WAF1/CIP1) transcriptional activity
      being regulated by SPRY2. Indeed, suppression of SPRY2 significantly increased
      p21(WAF1/CIP1) mRNA and protein expression as well as p21(WAF1/CIP1) promoter
      activity. Conversely, overexpressing SPRY2 triggered a decrease in p21(WAF1/CIP1)
      promoter activity. Concurrent down-regulation of both SPRY1 and SPRY2 also
      increased p21(WAF1/CIP1) expression in colon cancer cells. Increased nuclear
      localization of p21(WAF1/CIP1) in SPRY2 downregulated colon cancer cells may
      explain the inhibition of cell proliferation in colon cancer cells. Underscoring
      the biological relevance of these findings in SPRY1 and SPRY2 mutant mouse,
      recombination of floxed SPRY1 and SPRY2 alleles in mouse embryonic fibroblasts
      (MEFs) resulted in increased expression and nuclear localization of
      p21(WAF1/CIP1) and decreased cell proliferation. In CRC, the relationship of SPRY
      with p21 may provide unique strategies for cancer prevention and treatment. (c)
      2015 The Authors. Molecular Carcinogenesis published by Wiley Periodicals, Inc.

PMID- 26293892
TI  - Common toad Rhinella arenarum (Hensel, 1867) and its importance in assessing
      environmental health: test of micronuclei and nuclear abnormalities in
      erythrocytes.
AB  - Anthropogenic activities may generate significant changes in the integrity of
      aquatic ecosystems, so long-term monitoring of populations that inhabit them is
      crucial. Counting micronucleated erythrocytes (MN) and erythrocytic nuclear
      abnormalities (ENA) in peripheral blood is a widely used method for detecting
      chromosomal damage due to chemical agents in the water. We analyzed MN and ENA
      frequency in blood obtained from the common toad Rhinella arenarum populations in
      sites with different degrees of environmental degradation. The results of this
      study indicate that there is an association between the frequency of micronuclei
      and nuclear abnormalities and the degree of environmental alteration recorded for
      the sites studied. 

PMID- 26293893
TI  - Climate change effects on extreme flows of water supply area in Istanbul: utility
      of regional climate models and downscaling method.
AB  - This study investigates the climate change impact on the changes of mean and
      extreme flows under current and future climate conditions in the Omerli Basin of
      Istanbul, Turkey. The 15 regional climate model output from the EU-ENSEMBLES
      project and a downscaling method based on local implications from geophysical
      variables were used for the comparative analyses. Automated calibration algorithm
      is used to optimize the parameters of Hydrologiska Byrans Vattenbalansavdel-ning
      (HBV) model for the study catchment using observed daily temperature and
      precipitation. The calibrated HBV model was implemented to simulate daily flows
      using precipitation and temperature data from climate models with and without
      downscaling method for reference (1960-1990) and scenario (2071-2100) periods.
      Flood indices were derived from daily flows, and their changes throughout the
      four seasons and year were evaluated by comparing their values derived from
      simulations corresponding to the current and future climate. All climate models
      strongly underestimate precipitation while downscaling improves their
      underestimation feature particularly for extreme events. Depending on
      precipitation input from climate models with and without downscaling the HBV also
      significantly underestimates daily mean and extreme flows through all seasons.
      However, this underestimation feature is importantly improved for all seasons
      especially for spring and winter through the use of downscaled inputs. Changes in
      extreme flows from reference to future increased for the winter and spring and
      decreased for the fall and summer seasons. These changes were more significant
      with downscaling inputs. With respect to current time, higher flow magnitudes for
      given return periods will be experienced in the future and hence, in the planning
      of the Omerli reservoir, the effective storage and water use should be sustained.

PMID- 26293894
TI  - The statistical evaluation and comparison of ADMS-Urban model for the prediction
      of nitrogen dioxide with air quality monitoring network.
AB  - In many countries, road traffic is one of the main sources of air pollution
      associated with adverse effects on human health and environment. Nitrogen dioxide
      (NO2) is considered to be a measure of traffic-related air pollution, with
      concentrations tending to be higher near highways, along busy roads, and in the
      city centers, and the exceedances are mainly observed at measurement stations
      located close to traffic. In order to assess the air quality in the city and the
      air pollution impact on public health, air quality models are used. However,
      firstly, before the model can be used for these purposes, it is important to
      evaluate the accuracy of the dispersion modelling as one of the most widely used
      method. The monitoring and dispersion modelling are two components of air quality
      monitoring system (AQMS), in which statistical comparison was made in this
      research. The evaluation of the Atmospheric Dispersion Modelling System (ADMS
      Urban) was made by comparing monthly modelled NO2 concentrations with the data of
      continuous air quality monitoring stations in Kaunas city. The statistical
      measures of model performance were calculated for annual and monthly
      concentrations of NO2 for each monitoring station site. The spatial analysis was
      made using geographic information systems (GIS). The calculation of statistical
      parameters indicated a good ADMS-Urban model performance for the prediction of
      NO2. The results of this study showed that the agreement of modelled values and
      observations was better for traffic monitoring stations compared to the
      background and residential stations. 

PMID- 26293895
TI  - Inhibition of human 67-kDa laminin receptor sensitizes multidrug resistance colon
      cancer cell line SW480 for apoptosis induction.
AB  - The adhesion mediated drug resistance in cancer cells resulted from adhesion of
      the extracellular matrix is a major cause for multidrug resistance (MDR) and
      leads chemotherapeutic failure for colon cancer. In this study, we explored the
      role of 67-kDa laminin receptor (67LR) in chemotherapeutic drug resistance in
      colon cancer cells. SiRNA-mediated knockdown of 67LR decreased the cell adhesion
      when laminins were applied. Moreover, 67LR knockdown increased the expression of
      pro-apoptotic gene Bax but inhibited the expression of anti-apoptotic gene Bcl-2.
      Enhanced apoptosis was observed in 67LR siRNA-transfected SW480 cell when the
      cell was treated with doxorubicin for apoptosis induction. Furthermore, MTT assay
      revealed that the IC50 of chemotherapeutic toward SW480 cell adhesion to laminins
      was reduced after 67LR knockdown, indicating there was a significant increase of
      drug sensitivity in SW480 cell. In conclusion, our study demonstrated that 67LR
      plays a considerable role in the development of colon cancer MDR. 

PMID- 26293896
TI  - Loss of beta-arrestin1 expression predicts unfavorable prognosis for non-small
      cell lung cancer patients.
AB  - We aimed to study the expression status of beta-arrestin1 in non-small cell lung
      cancer (NSCLC) specimens and its clinicopathologic significance. The correlation
      between beta-arrestin1 and the tumor migration biomarker E-cadherin, as well as
      smoking index were studied. A total of 152 patients with NSCLC who undergone
      surgery were enrolled. Altogether, 88 lung squamous cell lung cancer (SCC)
      specimens and 64 adenocarcinoma (ADC) specimens were tested for
      immunohistochemistry. Patients' survival was analyzed by the Kaplan-Meier method.
      Univariate and multivariate analyses were performed to determine independent
      prognostic factors. Spearman rank correlation test was used to show data
      associations. For SCC patients, the expression of beta-arrestin1 was either lost
      (56 of 88, 63.6 %) or low (32 of 88, 36.4 %), which was significantly and
      negatively associated with E-cadherin expression (P = 0.017). The similar
      correlation existed between smoking index and beta-arrestin1 expression (P =
      0.044). For ADC patients, the deletion of beta-arrestin1 expression was rare (4
      of 64, 6.3 %). Loss of beta-arrestin1 expression indicated poorer survival for
      both SCC (P = 0.026) and ADC patients (P = 0.006). beta-arrestin1 expression was
      detected in the other ADC specimens but showed no significant correlation with
      survival. In SCC patients, the loss expression of beta-arrestin1 was frequently
      observed, and beta-arrestin1 expression was significantly correlated with the
      smoking index and E-cadherin expression, which all indicated beta-arrestin1's
      significant clinicopathologic role. However, beta-arrestin1 was expressed in most
      ADC patients, but its clinicopathologic role seemed to be obscure and might need
      further exploration. 

PMID- 26293897
TI  - IL-22 promotes the proliferation of cancer cells in smoking colorectal cancer
      patients.
AB  - Chronic cigarette smoking increases the risk of developing colorectal cancer
      (CRC) and causes higher mortality of CRC patients. To improve our understanding
      of the underlying mechanism and devise treatment strategies specifically targeted
      at chronic smoking CRC patients, we examined the immune system of healthy and CRC
      patients who are complete nonsmokers or chronic primary smokers. We found that
      the serum concentrations of CRC nonsmokers and CRC smokers were skewed toward
      Th17-type cytokines, including interleukin (IL)-17 and IL-22. Notably, smoking
      CRC subjects had significantly higher levels of IL-22 than nonsmoking CRC
      patients. We also observed higher percentages of CCR4(+)CCR6(+) Th17 cells in
      circulating blood and higher secretion of IL-17 and IL-22 by peripheral blood
      mononuclear cells (PBMCs) of nonsmoking CRC and smoking CRC patients, compared to
      healthy individuals. Again, we observed elevated IL-17 and IL-22 secretion by CRC
      smokers than nonsmokers. Since IL-22 has been shown to stimulate tumorigenesis,
      which was also replicated in our experiments using cancer cell line model, we
      tested whether CRC patients' cell culture supernatant could also support tumor
      growth using this model. We found that both HT29 cells and LoVo cells had the
      highest proliferation in the supernatant from smoking CRC patients. Moreover, the
      proliferation of LoVo cells in smoking CRC supernatant was significantly higher
      than that in nonsmoking CRC supernatant. In addition, we found that the IL-22
      concentration in normal gut tissue of the smoking CRC patients was significantly
      increased compared to that in nonsmoking CRC subjects, while no significant
      differences were observed in tumor tissues. Our results suggest that chronic
      smokers may have higher risk for CRC and worse prognosis due to dysregulated IL
      22 production. 

PMID- 26293899
TI  - The clinical utility of RFA in esophageal and cardia cancer patients with severe
      malignant obstruction.
AB  - Malignant obstruction of esophageal and cardia cancer greatly affects the
      prognosis and life quality of patients. However, no better regimens have been
      reported up to now. In recent years, radiofrequency ablation (RFA) has been
      prospectively proven in the management of some tumors. So, we investigated the
      impact of RFA on the malignant obstruction of esophageal and cardia cancer. In
      this study, we evaluated the operation duration, ablation duration, immediate
      compilations, etc., and followed up for 12 months. Our findings showed that there
      existed no technical problems in all 22 patients with a mean operation duration
      of 58 min and mean ablation duration of 23 min. No complication was observed in
      addition to postoperative low pressure in one patient and retrostenal pain in
      another patient. Importantly, all 22 patients obtained complete remission with
      normal diet and felt no sense of obstruction. Mean hospitalization time was 3
      days and then the 12-month follow-up continued. To our relief, re-obstruction was
      not observed in all patients for 2 months. In conclusion, the entire effect of
      RFA was satisfactory, and patients can obtain a better life quality, less pains,
      and complications. So RFA should be advocated and greatly investigated by more
      institutes and hospitals. 

PMID- 26293898
TI  - The anti-ovarian cancer activity by WYE-132, a mTORC1/2 dual inhibitor.
AB  - Epithelial ovarian cancer is the most common and lethal gynecological cancer in
      USA and around the world, causing major mortality annually. In the current study,
      we investigated the potential anti-ovarian cancer activity of WYE-132, a
      mammalian target of rapamycin (mTOR) complex 1/2 (mTORC1/2) dual inhibitor. Our
      results showed that WYE-132 potently inhibited proliferation of primary and
      established human ovarian cancer cells. Meanwhile, WYE-132 induced caspase
      dependent apoptosis in ovarian cancer cells. At the molecular level, WYE-132
      blocked mTORC1/2 activation and inhibited expression of mTOR-regulated genes
      (cyclin D1 and hypoxia-inducible factor 1alpha). Interestingly, introducing a
      constitutively active AKT (caAKT), which restored mTORC1/2 activation in WYE-132
      treated ovarian cancer cells, only mitigated (but not abolished) WYE-132-mediated
      growth inhibition and apoptosis. Further studies showed that WYE-132 inhibited
      sphingosine kinase-1 (SphK1) activity, leading to pro-apoptotic ceramide
      production in ovarian cancer cells. Meanwhile, WYE-132-induced cytotoxicity
      against ovarian cancer cells was inhibited by sphingosine-1-phosphate (S1P) but
      was aggravated by SphK1 inhibitor SKI-II or C6 ceramide. In vivo, WYE-132
      inhibited ovarian cancer cell growth, and its activity was further enhanced when
      co-administrated with paclitaxel (Taxol). These results demonstrate that WYE-132
      inhibits ovarian cancer cell proliferation through mTOR-dependent and mTOR
      independent mechanisms and indicate a potential value of WYE-132 in ovarian
      cancer treatment. 

PMID- 26293900
TI  - The role of life history traits in mammalian invasion success.
AB  - Why some organisms become invasive when introduced into novel regions while
      others fail to even establish is a fundamental question in ecology. Barriers to
      success are expected to filter species at each stage along the invasion pathway.
      No study to date, however, has investigated how species traits associate with
      success from introduction to spread at a large spatial scale in any group. Using
      the largest data set of mammalian introductions at the global scale and recently
      developed phylogenetic comparative methods, we show that human-mediated
      introductions considerably bias which species have the opportunity to become
      invasive, as highly productive mammals with longer reproductive lifespans are far
      more likely to be introduced. Subsequently, greater reproductive output and
      higher introduction effort are associated with success at both the establishment
      and spread stages. High productivity thus supports population growth and invasion
      success, with barriers at each invasion stage filtering species with
      progressively greater fecundity. 

PMID- 26293901
TI  - The Role of the Situation Model for Rereading Benefits in Korean-German
      Bilinguals.
AB  - This study examines whether rereading effects transfer across two different
      languages at the passage level. Fluent Korean-German bilinguals read passages
      twice either in the same language or a different language, and passages shared
      either words or situations. The dependent measure was the overall reading time
      for the second passage reading. Repetition effects were found only for passages
      in which situation models were preserved, although the translation altered the
      surface form and the textbase, demonstrating that the situation model plays an
      important role in bilingual repetition effects and that the context-dependent
      model Raney (Psychon Bull Rev 10:15-28, 2003) provides a theoretically meaningful
      guide for explaining rereading effects. 

PMID- 26293902
TI  - Underdiagnosis of depression in an economically deprived population in Macao,
      China.
AB  - INTRODUCTION: Previous literature revealed an association between low income and
      depression. Despite the availability of effective treatments, depression is often
      underdiagnosed and undertreated. This study was designed to evaluate the
      prevalence of depressive symptoms and their impact on health-related quality of
      life (HRQoL) in a low-income population in Macao. METHODS: This cross-sectional
      study targeted the adult beneficiaries of local food bank program. The program
      was established to provide food assistance to the residents who had low income
      but were ineligible for government financial assistance. All data were collected
      through interview and questionnaires. The Patient Health Questionnaire (PHQ-9)
      was used for assessing depressive symptoms. Information about depression
      diagnosis was obtained by the self-report method. HRQoL levels were measured by
      the 12-item Short-Form Health Survey, Version 2.0. RESULTS: A total of 272 study
      participants were included for analysis. Based on the PHQ-9 scores, 27.6% of the
      participants suffered from moderate to severe depressive symptoms. Among them,
      76% were not diagnosed with depression. Those with moderate to severe depressive
      symptoms had significantly lower levels of HRQoL (P < 0.001). Anxiety disorders
      (OR = 9.71, 95% CI = 2.36-40.06), migraine (OR = 3.88, 95% CI = 1.55-9.73), and
      poor to fair self-rated health (OR = 6.30, 95% CI = 1.95-20.40) were the
      independent factors associated with moderate to severe depressive symptoms.
      DISCUSSION: Underdiagnosis of depression was prevalent in this low-income
      population. There is a need to raise their awareness of mental disorders and
      improve their access to mental health services.

PMID- 26293903
TI  - Translational Research--Addressing the Challenge of Healthcare Transitions for
      Adolescents With Special Health Care Needs.

PMID- 26293904
TI  - A Clinical Home for Preexposure Prophylaxis: Diverse Health Care Providers'
      Perspectives on the "Purview Paradox".
AB  - BACKGROUND: One barrier to wider preexposure prophylaxis (PrEP) availability is
      uncertainty about the most appropriate providers and practice settings for
      offering PrEP. METHODS: The authors conducted in-depth interviews with 30
      clinicians--primary care and HIV specialists--in the New York City (NYC) region
      to explore issues related to PrEP rollout, including who should provide it and in
      what settings. RESULTS: A diverse group favored offering PrEP in non-HIV
      specialty settings in order to reach high-risk HIV-negative individuals. Yet, for
      each clinical skill or ancillary service deemed important for providing PrEP-
      knowledge of the medications, ability to assess and counsel around sexual risk
      behavior, and ability to provide support for retention and medication adherence-
      participants were divided in whether they thought primary care
      providers/practices could achieve it. Five participants strongly favored
      providing PrEP in HIV care practices. CONCLUSION: Although there may be multiple
      "homes" for PrEP, implementation research is needed to identify the most
      effective delivery approaches.

PMID- 26293905
TI  - HIV Viral Load Monitoring Frequency and Risk of Treatment Failure among
      Immunologically Stable HIV-Infected Patients Prescribed Combination
      Antiretroviral Therapy.
AB  - The authors sought to assess whether viral load (VL) monitoring frequency was
      associated with differential rates of virologic failure (VF) among HIV Outpatient
      Study (HOPS) participants seen during 1999 to 2013, who had maintained VL <50
      copies/mL, CD4 counts >=300 cells/mm(3), and been prescribed a stable combination
      antiretroviral regimen for at least 2 years. The authors required VL and CD4
      testing to have occurred regularly for the entire 2-year period. The authors
      assessed rates of VF comparing patients who maintained a frequent VL testing (>=3
      VLs) to those who shifted to a less frequent schedule (2 VL) after the 2-year
      period. Virologic failure was observed among 116 of 573 participants. The authors
      did not detect statistically significant difference in frequency of VF among
      patients undergoing frequent (21.0%) versus less frequent VL testing (19.6%),
      even after multivariable adjustment. Biannual VL monitoring for stable patients
      with aviremia could generate substantial cost savings without the increased risk
      of VF. 

PMID- 26293906
TI  - Effect of C-type natriuretic peptide on maturation and developmental competence
      of immature mouse oocytes in vitro.
AB  - In vitro maturation (IVM) of oocytes is an important assisted reproductive
      technology for infertility treatment and livestock breeding programs. Because of
      asynchronous nuclear and cytoplasmic maturation, the developmental competence of
      oocytes matured in vitro is compromised. C-Type natriuretic peptide (CNP), which
      has been proved to be an inhibitor of oocyte maturation, provides a new
      alternative to optimise synchronisation of nuclear and cytoplasmic maturation and
      improve developmental capacity of immature oocytes in vitro. To investigate the
      effect of temporary meiotic arrest mediated by CNP on maturation and subsequent
      development of immature oocytes, immature mouse oocytes from small antral
      follicles were temporarily arrested in meiosis by CNP (0, 5, 10 and 50nM) for 24h
      and then matured for 16h. CNP treatment significantly increased the oocyte
      maturation rate from less than half to above 80%. After IVF, temporary meiotic
      arrest mediated by 10 and 50nM CNP significantly improved fertilisation and
      blastocyst rate of oocytes matured in vitro up to approximately 55% and 30%
      respectively. Moreover, this positive effect of CNP was attributed, in part, to
      an increase in the number of mature oocytes with aligned chromosomes and a normal
      spindle. The present findings indicate the potential to use CNP to improve the
      efficiency of oocyte IVM.

PMID- 26293908
TI  - Collapsin response mediator protein 3 increases the dendritic arborization of
      hippocampal neurons.

PMID- 26293907
TI  - Expression of hepatic Fibroblast Growth Factor 19 is enhanced in Primary Biliary
      Cirrhosis and correlates with severity of the disease.
AB  - Cholestasis induces adaptive mechanisms protecting the liver against bile acids
      (BA) toxicity including modulation of BA synthesis. Whether fibroblast growth
      factor 19 (FGF19) or farnesoid X receptor (FXR) dependent signaling are involved
      in the regulation of BA homeostasis in primary biliary cirrhosis (PBC) remains
      unknown. Here we analyzed hepatic expression of FGF19 and other genes relevant to
      the adaptive response to cholestasis in tissues from non-cirrhotic (n = 24) and
      cirrhotic (n = 21) patients along with control tissues (n = 21). Moreover we
      searched for relationships between serum FGF19 and laboratory/clinical findings
      in 51 patients. Hepatic FGF19 mRNA expression was increased in non-cirrhotic and
      cirrhotic tissues (9-fold,p = 0.01; 69-fold,p < 0.0001, respectively). Protein
      levels of FGF19, FGF receptor 4, FXR and short heterodimer partner were increased
      in cirrhotic livers (9-fold, p < 0.001; 3.5-fold,p = 0.007; 2.4-fold,p < 0.0001;
      2.8-fold,p < 0.0001 vs controls, respectively) which was accompanied by down
      regulation of CYP7A1 (50% reduction, p = 0.006). Serum and liver levels of FGF19
      correlated with worse liver biochemistry, BAs, quality of life and Mayo Risk
      Score. Serum FGF19 was elevated in UDCA non-responders. We conclude that PBC
      induces characteristic changes in liver expression of BAs synthesis regulatory
      molecules. FGF19 correlates with severity of liver disease and can potentially
      serve as an indicator of chronic cholestatic liver injury. 

PMID- 26293909
TI  - Social influences on unconscious plagiarism and anti-plagiarism.
AB  - People are more likely to unconsciously plagiarise ideas from a same-sex partner
      than a different-sex partner, and more likely to unconsciously plagiarise if
      recalling alone rather than in the presence of their partner [Macrae, C. N.,
      Bodenhausen, G. V., & Calvini, G. (1999). Contexts of cryptomnesia: May the
      source be with you. Social Cognition, 17, 273-297. doi:
      10.1521/soco.1999.17.3.273 ]. Two sets of experiments explore these phenomena,
      using extensions of the standard unconscious plagiarism paradigm. In Experiment
      1A participants worked together in same- or different-sex dyads before trying to
      recall their own ideas or their partner's ideas. More source errors were evident
      for same-sex dyads (Experiment 1A), but this effect was absent when participants
      recalled from both sources simultaneously (Experiment 1B). In Experiment 2A,
      participants recalled ideas from a single source either alone or in the presence
      of the partner, using an extended-recall task. Partner presence did not affect
      the availability of ideas, but did reduce the propensity to report them as task
      compliant, relative to a partner-present condition. Simultaneous recall from both
      sources removed this social effect (Experiment 2B). Thus social influences on
      unconscious plagiarism are apparent, but are influenced by the salience of the
      alternate source at retrieval.

PMID- 26293910
TI  - Characterization of the effects of C-terminal pro-sequence on self-inactivation
      of Stereum purpureum endopolygalacturonase I.
AB  - Endpolygalacturonase I from Stereum purpureum has been identified as a causative
      substance for the silver-leaf disease in apples. It possesses a unique pro
      sequence in the C-terminal region that lacks endpolygalacturonases from any other
      origin. In this study, we analyzed and compared enzymatic characteristics between
      pro-form (pro-endoPG I) and mature form processed by V8 protease (endoPG I) and
      described the suppression activity of the pro-sequence. Of note, the optimal pH
      for pro-endoPG I activity shifted to pH 4.0 from pH 4.5-5.0 of endoPG I. The
      kinetic parameters indicated that the activity inhibition resulted from a pH
      independent decrease of substrate affinity and pH-dependent deterioration of
      velocity by the pro-sequence. Analysis of site-directed mutations within pro
      endoPG I showed that its alpha-helical structure includes two glutamates (E364
      and E366) and alanine (A365), and its orientation by prolines (especially P348)
      in the pro-sequence played a significant role in its suppression activity. As for
      mutations in the mature domain, a marked reduction of suppression was observed
      for enzymes with mutations in H150, R220 and K253, indicating that the pro
      sequence interacts with the active cleft by a few ionic bonds. 

PMID- 26293911
TI  - Motility modulation by the small non-coding RNA SroC in Salmonella Typhimurium.
AB  - Bacterial regulatory networks of gene expression include the interaction of
      diverse types of molecules such as the small non-coding RNAs (sRNAs) and their
      cognate messenger RNAs (mRNAs). In this study, we demonstrated that the
      Salmonella Typhimurium sRNA SroC is significantly expressed between the late
      exponential and stationary phase of growth in an rpoS-dependent manner. The
      expression of flagellar genes predicted as targets of this sRNA was
      quantitatively analyzed in both a DeltasroC mutant and a SroC-overexpressing
      (pSroC) strain. Deletion of sroC increased flagellar gene expression (i.e. flhBAE
      and fliE). Conversely, overexpression of SroC reduced flhBAE and fliE expression.
      These observations correlated with phenotypic evaluation of motility, where sroC
      deletion slightly increased motility, which in turn, was drastically reduced upon
      overexpression of SroC. The effects of deletion and overexpression of sroC in
      biofilm formation were also examined, where the DeltasroC and pSroC strains
      exhibited a reduced and increased ability to form biofilm, respectively.
      Furthermore, electron microscopy revealed that the wild-type strain
      overexpressing SroC had a non-flagellated phenotype. Taken together, our results
      showed that S. Typhimurium sRNA SroC modulates the flagellar synthesis by down
      regulating the expression of flhBAE and fliE genes. 

PMID- 26293912
TI  - An ethanolamine kinase Eki1 affects radial growth and cell wall integrity in
      Trichoderma reesei.
AB  - Ethanolamine kinase (ATP:ethanolamine O-phosphotransferase, EC 2.7.1.82)
      catalyzes the committed step of phosphatidylethanolamine synthesis via the CDP
      ethanolamine pathway. The functions of eki genes that encode ethanolamine kinase
      have been intensively studied in mammalian cells, fruit flies and yeast. However,
      the role of the eki gene has not yet been characterized in filamentous fungi. In
      this study, Treki1, an ortholog of Saccharomyces cerevisiae EKI1, was identified
      and functionally characterized using a target gene deletion strategy in
      Trichoderma reesei. A Treki deletion mutant was less sensitive to cell wall
      stressors calcofluor white and Congo red and released fewer protoplasts during
      cell wall digestion than the parent strain QM9414. Further transcription analysis
      showed that the expression levels of five genes that encode chitin synthases were
      drastically increased in the DeltaTreki1 mutant. The chitin content was also
      increased in the null mutant of Treki1 comparing to the parent strain. In
      addition, the DeltaTreki1 mutant exhibited defects in radial growth, conidiation
      and the accumulation of ethanolamine. The results indicate that Treki1 plays a
      key role in growth and development and in the maintenance of cell wall integrity
      in T. reesei. 

PMID- 26293913
TI  - Catalytic function of the mycobacterial binuclear iron monooxygenase in acetone
      metabolism.
AB  - Mycobacteria such as Mycobacterium smegmatis strain mc(2)155 and Mycobacterium
      goodii strain 12523 are able to grow on acetone and use it as a source of carbon
      and energy. We previously demonstrated by gene deletion analysis that the mimABCD
      gene cluster, which encodes a binuclear iron monooxygenase, plays an essential
      role in acetone metabolism in these mycobacteria. In the present study, we
      determined the catalytic function of MimABCD in acetone metabolism. Whole-cell
      assays were performed using Escherichia coli cells expressing the MimABCD
      complex. When the recombinant E. coli cells were incubated with acetone, a
      product was detected by gas chromatography (GC) analysis. Based on the retention
      time and the gas chromatography-mass spectrometry (GC-MS) spectrum, the reaction
      product was identified as acetol (hydroxyacetone). The recombinant E. coli cells
      produced 1.02 mM of acetol from acetone within 24 h. Furthermore, we demonstrated
      that MimABCD also was able to convert methylethylketone (2-butanone) to 1-hydroxy
      2-butanone. Although it has long been known that microorganisms such as
      mycobacteria metabolize acetone via acetol, this study provides the first
      biochemical evidence for the existence of a microbial enzyme that catalyses the
      conversion of acetone to acetol.

PMID- 26293914
TI  - Properties and evolution of emission in molecular aggregates of a perylene
      ammonium derivative in polymer matrices.
AB  - Size-dependent fluorescent properties of aggregates of a perylene ammonium
      derivative (PeryAm) were studied by steady-state and time-resolved spectroscopic
      methods. Quantitative analyses of aggregated states in aqueous solution indicated
      that the aggregation proceeded through dimer units of PeryAm. The fluorescence of
      the aggregate in the PVA film prepared from the aqueous solution continuously
      redshifted with an increase in the concentration of PeryAm in the mother liquor
      while keeping the absorption spectra in almost the same band shapes. Fluorescence
      anisotropy values of aggregates in the PVA film were dependent on the monitoring
      wavelength, and time profiles of the fluorescence at longer wavelengths showed a
      rapid increase just after the pulsed excitation. These results indicated
      efficient energy transfer to the stable sites in aggregates. Fluorescence
      microscopy images showed that aggregates were segregated in the PVA film and the
      color of the emission was dependent on the size of the aggregate. Under the
      steady-state irradiation, the emission color of the aggregates changed from green
      to yellow, which was attributable to the association of a small cluster of PeryAm
      with the green emission resulting in the formation of yellow-colored aggregates.
      On the basis of these results, we have discussed the mechanisms and dynamics of
      the aggregation and size-dependent emission in aggregates. 

PMID- 26293915
TI  - Knee buckling (negative myoclonus) associated with clozapine: Is there a dose
      threshold?

PMID- 26293922
TI  - PtdIns(3,4,5)P3-Dependent Activation of the mTORC2 Kinase Complex.
AB  - mTOR serves as a central regulator of cell growth and metabolism by forming two
      distinct complexes, mTORC1 and mTORC2. Although mechanisms of mTORC1 activation
      by growth factors and amino acids have been extensively studied, the upstream
      regulatory mechanisms leading to mTORC2 activation remain largely elusive. Here,
      we report that the pleckstrin homology (PH) domain of SIN1, an essential and
      unique component of mTORC2, interacts with the mTOR kinase domain to suppress
      mTOR activity. More importantly, PtdIns(3,4,5)P3, but not other PtdInsPn species,
      interacts with SIN1-PH to release its inhibition on the mTOR kinase domain,
      thereby triggering mTORC2 activation. Mutating critical SIN1 residues that
      mediate PtdIns(3,4,5)P3 interaction inactivates mTORC2, whereas mTORC2 activity
      is pathologically increased by patient-derived mutations in the SIN1-PH domain,
      promoting cell growth and tumor formation. Together, our study unravels a PI3K
      dependent mechanism for mTORC2 activation, allowing mTORC2 to activate AKT in a
      manner that is regulated temporally and spatially by PtdIns(3,4,5)P3.
      SIGNIFICANCE: The SIN1-PH domain interacts with the mTOR kinase domain to
      suppress mTOR activity, and PtdIns(3,4,5)P3 binds the SIN1-PH domain to release
      its inhibition on the mTOR kinase domain, leading to mTORC2 activation. Cancer
      patient-derived SIN1-PH domain mutations gain oncogenicity by loss of suppressing
      mTOR activity as a means to facilitate tumorigenesis.

PMID- 26293923
TI  - Acute Traumatic Coagulopathy Accompanying Isolated Traumatic Brain Injury is
      Associated with Worse Long-Term Functional and Cognitive Outcomes.
AB  - BACKGROUND: Approximately one-third of patients with isolated traumatic brain
      injury (iTBI) present with acute traumatic coagulopathy (ATC). ATC is associated
      with increased morbidity and mortality. Its effects on long-term functional and
      cognitive outcomes are not as well characterized. METHODS: Data from the
      Citicoline Brain Injury Treatment Trial (COBRIT) were analyzed retrospectively.
      Exclusion criteria were renal failure or malignancy, and any extracranial injury
      severity score >3. ATC was defined as INR > 1.3, PTT > 38 s, or platelets < 100
      K, determined at baseline, and during the first 7 days of hospitalization.
      RESULTS: Six hundred forty-seven patients were included; 21 % were found to have
      ATC. Highest incidence occurred at baseline, and Day Two. Forty-two percent of
      ATC patients had a GCS < 8, compared with 11.3 % of non-ATC patients (p < 0.001).
      A significantly higher proportion of ATC patients was transfused blood products,
      required greater than 4L of fluids, demonstrated hyperthermia and hypothermia,
      were hypotensive and demonstrated elevated lactate when compared to non-ATC
      patients. In-hospital mortality, mean hospital length of stay, incidence of DVT
      and seizures were also significantly higher in ATC patients. A significantly
      lower portion of ATC patients had good outcomes on the GOS-E (i.e., score > 6),
      and the DRS (i.e., score < 2) at 180 days, for which ATC was found to be an
      independent predictor with binary logistic regression. ATC patients also
      performed significantly worse on several components of the CVLT-II at 180 days.
      CONCLUSIONS: ATC accompanying iTBI is associated with worse functional and
      cognitive outcomes at 180 days.

PMID- 26293924
TI  - Effect of distraction osteogenesis in patient with tibial shortening after
      initial union of Congenital Pseudarthrosis of the Tibia (CPT): a preliminary
      study.
AB  - BACKGROUND: The purpose of our retrospective study was to evaluate the
      preliminary result of distraction osteogenesis in patient with tibial shortening
      after initial union of Congenital Pseudarthrosis of the Tibia (CPT). METHODS: All
      the CPT cases with tibial shortening after initial union managed by proximal
      tibial lengthening using Ilizarov technique were identified. All the patient
      charts and radiograms were reviewed. RESULTS: Between March 2007 and January
      2012, 11 CPT cases were included with an average follow-up of 41 months (range,
      34-51 months). The mean age at surgery was 8.5 years (range, 3.9-14.5y). The
      average length of discrepancy was 5.6 cm (range, 2.0-8.2 cm). Eight (8) cases had
      radiological findings of proximal tibial dysplasia, while the other 3 cases had
      not. The average distraction length gained was 5.3 cm (range, 3.5-8.0 cm) with a
      mean elongation rate of 21.4% (range, 15-30%). The Healing Index (HI) was 63.1
      d/cm (range, 47-77 d/cm). In the 8 patients with proximal tibial dysplasia, 5
      cases had lateral callus, 3 had central callus, and poor bone regeneration was
      observed in all of them with an average HI of 67 d/cm. In the other 3 patients
      without proximal tibial dysplasia, concave shaped callus was identified with an
      average HI of 52.7 d/cm. None of the patients had re-fracture, nonunion, axis
      deviation or angulation of the distraction area. Ankle joint stiffness was found
      in 2 of the patients. No evidence of knee contracture was detected. There were 5
      cases with pin-tract infection which was managed by pin-tract nurse and oral
      administration of antibiotics. CONCLUSIONS: We concluded that proximal tibial
      lengthening after initial union of CPT was effective for management of tibial
      shortening, however it was characterized by poor bone regeneration with different
      types of callus from normal, greater healing index and prolonged fixator wearing.
      We recommended that tibial lengthening could be considered when the limb length
      discrepancy (LLD) was more than 4 cm in younger children after primary union of
      CPT.

PMID- 26293926
TI  - Interplay between pathogenicity island carriage, resistance profile and plasmid
      acquisition in uropathogenic Escherichia coli.
AB  - This study aimed to characterize the relationship between pathogenicity islands
      (PAIs), single virulence genes and resistance among uropathogenic Escherichia
      coli, evaluating the resistance plasmid carriage fitness cost related to PAIs.
      For 65 urinary E. coli, antimicrobial susceptibility and extended-spectrum beta
      lactamase production were determined with the Vitek 2 Advanced Expert system.
      Phylogroup determination, detection of PAIs and virulence genes papAH, papC,
      sfa/foc, afa/dra, iutA, kpsMII, cnf1, eaeA, hlyA, stx1 and stx2, plasmid replicon
      typing and screening for plasmidic resistance determinants qnr, aac(6')-Ib-cr,
      qepA and bla(CTX-M) were carried out by PCR. Conjugation was performed between a
      donor carrying IncF, IncK and bla(CTX-M-15), and receptors carrying one to six
      PAIs. The relative fitness of transconjugants was estimated by pairwise
      competition experiments. PAI IV(536) (68 %), gene iutA (57 %) and resistance to
      ampicillin were the most prevalent traits. PAI I(536), PAI II(536), PAI III(536)
      and PAI II(J96) were exclusively associated with susceptibility to
      amoxicillin/clavulanic acid, cefotaxime, ceftazidime, ciprofloxacin, gentamicin
      and trimethoprim/sulfamethoxazole, and were more prevalent in strains susceptible
      to ampicillin and cefalotin. PAI IV(536), PAI II(CFT073) and PAI I(CFT073) were
      more prevalent among isolates showing resistance to amoxicillin/clavulanic acid,
      cefalotin, cefotaxime, ceftazidime and gentamicin. An inverse relationship was
      observed between the number of plasmids and the number of PAIs carried.
      Transconjugants were obtained for receptors carrying three or fewer PAIs. The
      mean relative fitness rates of these transconjugants were 0.87 (two PAIs), 1.00
      (one PAI) and 1.09 (three PAI). The interplay between resistance, PAI carriage
      and fitness cost of plasmid acquisition could be considered PAI specific, and not
      necessarily associated with the number of PAIs.

PMID- 26293925
TI  - Observer blind randomised controlled trial of a tailored home exercise programme
      versus usual care in people with stable inflammatory immune mediated neuropathy.
AB  - BACKGROUND: Inflammatory neuropathies such as Guillain-Barre syndrome, chronic
      inflammatory demyelinating polyradiculoneuropathy and paraproteinaemic
      demyelinating neuropathy are a heterogenous group of peripheral nerve disorders
      that affect around one to two people per 100,000. Whilst treatments such as
      intravenous immunoglobulin, plasma exchange and corticosteroids have generally
      positive results, long-term residual symptoms and associated activity limitations
      are common. There is currently no standardised care for patients with ongoing
      activity limitation and participation restriction as a result of inflammatory
      neuropathy IN but data from observational studies and a randomised controlled
      trial suggest that exercise either alone or as part of a multidisciplinary
      rehabilitation programme may be beneficial in improving activity limitation.
      Tailoring the intervention for participants following physiotherapy assessment
      and incorporating patient preference for type and location of exercise may be
      important. METHODS/DESIGN: The current study is a pragmatic, prospective,
      parallel observer-blind, randomised controlled trial to evaluate the efficacy and
      cost-effectiveness of a twelve week tailored home exercise programme versus
      advice and usual care. Seventy adults with stable immune mediated inflammatory
      neuropathy IN will be recruited to the study from two main sources: patients
      attending selected specialist peripheral nerve clinics in the South East and West
      Midlands of England and people with who access the GAIN charity website or
      newsletter. Participants will be randomised to receive either advice about
      exercise and usual care or a 12 week tailored home exercise programme. The
      primary outcome of activity limitation and secondary outcomes of fatigue, quality
      of life, self-efficacy, illness beliefs, mood and physical activity will be
      assessed via self-report questionnaire at baseline, 12 weeks and 12 months post
      intervention. Cost effectiveness and cost utility will be assessed via interview
      at baseline and 12 months post intervention. Intention to treat analysis will be
      our primary model for efficacy analysis. Semi-structured interviews will be
      conducted with a selected sample of participants in order to explore the
      acceptability of the intervention and factors affecting adherence to the exercise
      programme. DISCUSSION: This is the first randomised controlled trial to compare
      the efficacy and cost-effectiveness of tailored home exercise with advice about
      exercise and usual care for adults with inflammatory neuropathy. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN13311697.

PMID- 26293927
TI  - Assessing fidelity to treatment delivery in the ICONS (Identifying Continence
      OptioNs after Stroke) cluster randomised feasibility trial.
AB  - BACKGROUND: The implementation of strategies to monitor and enhance treatment
      fidelity is of paramount importance in trials of complex interventions. A recent
      framework published by the National Institutes of Health Behavior Change
      Consortium recommends addressing five areas of treatment fidelity, one of which
      is delivery of treatment. This study aimed to explore fidelity to treatment
      delivery of the ICONS intervention (a systematic voiding programme [SVP]). This
      included exploring the feasibility of a method to assess fidelity to treatment
      delivery and collecting preliminary evidence of the level of fidelity to SVP
      delivery in order to inform strategies for improving fidelity in a future trial.
      METHODS: Delivery of treatment was recorded by nurses through completion of daily
      clinical logs, which included: a voiding interval, proposed voiding times and
      actual voiding times. The a priori method for assessment of fidelity - comparing
      actual voiding times with proposed voiding times - was trialled on a small amount
      of data. Due to errors in documentation of the voiding intervals and proposed
      voiding times it was not possible to assess fidelity directly as planned. A new
      method was devised, which included identification of 'key quality indicators'.
      RESULTS: This new approach to assessing fidelity used key quality indicators
      based upon presence of the data needed to make the comparison between proposed
      and actual voiding times. The proportion of clinical logs with correct
      documentation of voiding intervals and proposed voiding times was less than 40 %.
      For clinical logs with correct documentation, an actual voiding time within 30
      min of the proposed voiding time was identified on approximately 55 % of
      occasions. CONCLUSIONS: Lessons learnt from this study have implications for the
      future ICONS definitive trial and for other trials of complex interventions.
      Implementation of a complex intervention may often deviate from what is intended.
      While careful consideration should be given to the best method of fidelity
      assessment, an iterative approach allowing flexibility to adapt pre-planned
      methods is recommended within feasibility trials. As fidelity to treatment
      delivery in the ICONS feasibility trial appeared to be relatively low, more
      attention to implementation strategies will be required in the definitive trial.
      TRIAL REGISTRATION: Identifier: ISRCTN08609907 ; date registered: 07/07/2010.

PMID- 26293930
TI  - ENERGY DEVELOPMENT. Big Archaeology fights Big Oil to preserve ancient landscape.

PMID- 26293928
TI  - Forestry in the Anthropocene.

PMID- 26293931
TI  - POLAR SCIENCE. War over Belgian polar station.

PMID- 26293932
TI  - ANIMAL WELFARE. New rules may end U.S. chimpanzee research.

PMID- 26293933
TI  - ENERGY. As Arctic drilling starts, Shell-funded researchers keep watch.

PMID- 26293934
TI  - BEHIND THE NUMBERS. Rethinking the time 'lost' to red tape.

PMID- 26293935
TI  - The supplement sleuth.

PMID- 26293936
TI  - ECOLOGY. A most unusual (super)predator.

PMID- 26293937
TI  - ASTROPHYSICS. Probing the dark side.

PMID- 26293938
TI  - MICROBIOME. Plant microbiome blueprints.

PMID- 26293939
TI  - CELL SIGNALING. Lipids link ion channels and cancer.

PMID- 26293940
TI  - MEDICINE. Global control of hepatitis C virus.

PMID- 26293941
TI  - BIOSECURITY. Assessing the bioweapons threat.

PMID- 26293942
TI  - BIOTECHNOLOGY. Genetically engineered trees: Paralysis from good intentions.

PMID- 26293943
TI  - Isolated tribes: Contact misguided.

PMID- 26293944
TI  - Isolated tribes: Human rights first.

PMID- 26293945
TI  - Drought threatens California's levees.

PMID- 26293946
TI  - GEOMORPHOLOGY. Comment on "Tectonic control of Yarlung Tsangpo Gorge revealed by
      a buried canyon in Southern Tibet".
AB  - Wang et al. (Reports, 21 November, 2014, p. 978) describe a buried canyon
      upstream of the Yarlung Tsangpo Gorge and argue that rapid erosion of the gorge
      was merely a passive response to rapid uplift at ~2.5 million years ago (Ma). We
      view these data as an expected consequence emerging from feedbacks between
      erosion and crustal rheology active well before 2.5 Ma. 

PMID- 26293947
TI  - GEOMORPHOLOGY. Response to Comment on "Tectonic control of Yarlung Tsangpo Gorge
      revealed by a buried canyon in Southern Tibet".
AB  - In their Comment, Zeitler et al. do not challenge our results or interpretation.
      Our study does not disprove coupling between tectonic uplift and erosion but
      suggests that this coupling cannot be the sole explanation of rapid uplift in the
      Himalayan syntaxes. 

PMID- 26293948
TI  - Forest health. Forest health in a changing world. Introduction.

PMID- 26293949
TI  - FOREST HEALTH. Battling a giant killer.

PMID- 26293950
TI  - FOREST HEALTH. The new North.

PMID- 26293951
TI  - FOREST HEALTH. Second Act.

PMID- 26293952
TI  - Forest health and global change.
AB  - Humans rely on healthy forests to supply energy, building materials, and food and
      to provide services such as storing carbon, hosting biodiversity, and regulating
      climate. Defining forest health integrates utilitarian and ecosystem measures of
      forest condition and function, implemented across a range of spatial scales.
      Although native forests are adapted to some level of disturbance, all forests now
      face novel stresses in the form of climate change, air pollution, and invasive
      pests. Detecting how intensification of these stresses will affect the trajectory
      of forests is a major scientific challenge that requires developing systems to
      assess the health of global forests. It is particularly critical to identify
      thresholds for rapid forest decline, because it can take many decades for forests
      to restore the services that they provide. 

PMID- 26293953
TI  - Boreal forest health and global change.
AB  - The boreal forest, one of the largest biomes on Earth, provides ecosystem
      services that benefit society at levels ranging from local to global. Currently,
      about two-thirds of the area covered by this biome is under some form of
      management, mostly for wood production. Services such as climate regulation are
      also provided by both the unmanaged and managed boreal forests. Although most of
      the boreal forests have retained the resilience to cope with current
      disturbances, projected environmental changes of unprecedented speed and
      amplitude pose a substantial threat to their health. Management options to reduce
      these threats are available and could be implemented, but economic incentives and
      a greater focus on the boreal biome in international fora are needed to support
      further adaptation and mitigation actions. 

PMID- 26293954
TI  - Temperate forest health in an era of emerging megadisturbance.
AB  - Although disturbances such as fire and native insects can contribute to natural
      dynamics of forest health, exceptional droughts, directly and in combination with
      other disturbance factors, are pushing some temperate forests beyond thresholds
      of sustainability. Interactions from increasing temperatures, drought, native
      insects and pathogens, and uncharacteristically severe wildfire are resulting in
      forest mortality beyond the levels of 20th-century experience. Additional
      anthropogenic stressors, such as atmospheric pollution and invasive species,
      further weaken trees in some regions. Although continuing climate change will
      likely drive many areas of temperate forest toward large-scale transformations,
      management actions can help ease transitions and minimize losses of socially
      valued ecosystem services. 

PMID- 26293955
TI  - Increasing human dominance of tropical forests.
AB  - Tropical forests house over half of Earth's biodiversity and are an important
      influence on the climate system. These forests are experiencing escalating human
      influence, altering their health and the provision of important ecosystem
      functions and services. Impacts started with hunting and millennia-old megafaunal
      extinctions (phase I), continuing via low-intensity shifting cultivation (phase
      II), to today's global integration, dominated by intensive permanent agriculture,
      industrial logging, and attendant fires and fragmentation (phase III). Such
      ongoing pressures, together with an intensification of global environmental
      change, may severely degrade forests in the future (phase IV, global
      simplification) unless new "development without destruction" pathways are
      established alongside climate change-resilient landscape designs. 

PMID- 26293956
TI  - Planted forest health: The need for a global strategy.
AB  - Several key tree genera are used in planted forests worldwide, and these
      represent valuable global resources. Planted forests are increasingly threatened
      by insects and microbial pathogens, which are introduced accidentally and/or have
      adapted to new host trees. Globalization has hastened tree pest emergence,
      despite a growing awareness of the problem, improved understanding of the costs,
      and an increased focus on the importance of quarantine. To protect the value and
      potential of planted forests, innovative solutions and a better-coordinated
      global approach are needed. Mitigation strategies that are effective only in
      wealthy countries fail to contain invasions elsewhere in the world, ultimately
      leading to global impacts. Solutions to forest pest problems in the future should
      mainly focus on integrating management approaches globally, rather than single
      country strategies. A global strategy to manage pest issues is vitally important
      and urgently needed. 

PMID- 26293957
TI  - QUANTUM SIMULATION. Localization-delocalization transition in the dynamics of
      dipolar-coupled nuclear spins.
AB  - Nonequilibrium dynamics of many-body systems are important in many scientific
      fields. Here, we report the experimental observation of a phase transition of the
      quantum coherent dynamics of a three-dimensional many-spin system with dipolar
      interactions. Using nuclear magnetic resonance (NMR) on a solid-state system of
      spins at room-temperature, we quench the interaction Hamiltonian to drive the
      evolution of the system. Depending on the quench strength, we then observe either
      localized or extended dynamics of the system coherence. We extract the critical
      exponents for the localized cluster size of correlated spins and diffusion
      coefficient around the phase transition separating the localized from the
      delocalized dynamical regime. These results show that NMR techniques are well
      suited to studying the nonequilibrium dynamics of complex many-body systems. 

PMID- 26293958
TI  - ASTROPHYSICS. Atom-interferometry constraints on dark energy.
AB  - If dark energy, which drives the accelerated expansion of the universe, consists
      of a light scalar field, it might be detectable as a "fifth force" between normal
      matter objects, in potential conflict with precision tests of gravity. Chameleon
      fields and other theories with screening mechanisms, however, can evade these
      tests by suppressing the forces in regions of high density, such as the
      laboratory. Using a cesium matter-wave interferometer near a spherical mass in an
      ultrahigh-vacuum chamber, we reduced the screening mechanism by probing the field
      with individual atoms rather than with bulk matter. We thereby constrained a wide
      class of dark energy theories, including a range of chameleon and other theories
      that reproduce the observed cosmic acceleration. 

PMID- 26293960
TI  - ECOLOGICAL THEORY. A general consumer-resource population model.
AB  - Food-web dynamics arise from predator-prey, parasite-host, and herbivore-plant
      interactions. Models for such interactions include up to three consumer activity
      states (questing, attacking, consuming) and up to four resource response states
      (susceptible, exposed, ingested, resistant). Articulating these states into a
      general model allows for dissecting, comparing, and deriving consumer-resource
      models. We specify this general model for 11 generic consumer strategies that
      group mathematically into predators, parasites, and micropredators and then
      derive conditions for consumer success, including a universal saturating
      functional response. We further show how to use this framework to create simple
      models with a common mathematical lineage and transparent assumptions. Underlying
      assumptions, missing elements, and composite parameters are revealed when classic
      consumer-resource models are derived from the general model. 

PMID- 26293959
TI  - ASTROPHYSICS. Exclusion of leptophilic dark matter models using XENON100
      electronic recoil data.
AB  - Laboratory experiments searching for galactic dark matter particles scattering
      off nuclei have so far not been able to establish a discovery. We use data from
      the XENON100 experiment to search for dark matter interacting with electrons.
      With no evidence for a signal above the low background of our experiment, we
      exclude a variety of representative dark matter models that would induce
      electronic recoils. For axial-vector couplings to electrons, we exclude cross
      sections above 6 * 10(-35) cm(2) for particle masses of m(chi) = 2 GeV/c(2).
      Independent of the dark matter halo, we exclude leptophilic models as an
      explanation for the long-standing DAMA/LIBRA signal, such as couplings to
      electrons through axial-vector interactions at a 4.4sigma confidence level,
      mirror dark matter at 3.6sigma, and luminous dark matter at 4.6sigma.

PMID- 26293961
TI  - HUMAN IMPACTS. The unique ecology of human predators.
AB  - Paradigms of sustainable exploitation focus on population dynamics of prey and
      yields to humanity but ignore the behavior of humans as predators. We compared
      patterns of predation by contemporary hunters and fishers with those of other
      predators that compete over shared prey (terrestrial mammals and marine fishes).
      Our global survey (2125 estimates of annual finite exploitation rate) revealed
      that humans kill adult prey, the reproductive capital of populations, at much
      higher median rates than other predators (up to 14 times higher), with
      particularly intense exploitation of terrestrial carnivores and fishes. Given
      this competitive dominance, impacts on predators, and other unique predatory
      behavior, we suggest that humans function as an unsustainable "super predator,"
      which-unless additionally constrained by managers-will continue to alter
      ecological and evolutionary processes globally.

PMID- 26293962
TI  - PARASITIC PLANTS. Probing strigolactone receptors in Striga hermonthica with
      fluorescence.
AB  - Elucidating the signaling mechanism of strigolactones has been the key to
      controlling the devastating problem caused by the parasitic plant Striga
      hermonthica. To overcome the genetic intractability that has previously
      interfered with identification of the strigolactone receptor, we developed a
      fluorescence turn-on probe, Yoshimulactone Green (YLG), which activates
      strigolactone signaling and illuminates signal perception by the strigolactone
      receptors. Here we describe how strigolactones bind to and act via ShHTLs, the
      diverged family of alpha/beta hydrolase-fold proteins in Striga. Live imaging
      using YLGs revealed that a dynamic wavelike propagation of strigolactone
      perception wakes up Striga seeds. We conclude that ShHTLs function as the
      strigolactone receptors mediating seed germination in Striga. Our findings enable
      access to strigolactone receptors and observation of the regulatory dynamics for
      strigolactone signal transduction in Striga. 

PMID- 26293963
TI  - An alternative splicing event amplifies evolutionary differences between
      vertebrates.
AB  - Alternative splicing (AS) generates extensive transcriptomic and proteomic
      complexity. However, the functions of species- and lineage-specific splice
      variants are largely unknown. Here we show that mammalian-specific skipping of
      polypyrimidine tract-binding protein 1 (PTBP1) exon 9 alters the splicing
      regulatory activities of PTBP1 and affects the inclusion levels of numerous
      exons. During neurogenesis, skipping of exon 9 reduces PTBP1 repressive activity
      so as to facilitate activation of a brain-specific AS program. Engineered
      skipping of the orthologous exon in chicken cells induces a large number of
      mammalian-like AS changes in PTBP1 target exons. These results thus reveal that a
      single exon-skipping event in an RNA binding regulator directs numerous AS
      changes between species. Our results further suggest that these changes
      contributed to evolutionary differences in the formation of vertebrate nervous
      systems. 

PMID- 26293964
TI  - SIGNAL TRANSDUCTION. Membrane potential modulates plasma membrane phospholipid
      dynamics and K-Ras signaling.
AB  - Plasma membrane depolarization can trigger cell proliferation, but how membrane
      potential influences mitogenic signaling is uncertain. Here, we show that plasma
      membrane depolarization induces nanoscale reorganization of phosphatidylserine
      and phosphatidylinositol 4,5-bisphosphate but not other anionic phospholipids. K
      Ras, which is targeted to the plasma membrane by electrostatic interactions with
      phosphatidylserine, in turn undergoes enhanced nanoclustering. Depolarization
      induced changes in phosphatidylserine and K-Ras plasma membrane organization
      occur in fibroblasts, excitable neuroblastoma cells, and Drosophila neurons in
      vivo and robustly amplify K-Ras-dependent mitogen-activated protein kinase (MAPK)
      signaling. Conversely, plasma membrane repolarization disrupts K-Ras
      nanoclustering and inhibits MAPK signaling. By responding to voltage-induced
      changes in phosphatidylserine spatiotemporal dynamics, K-Ras nanoclusters set up
      the plasma membrane as a biological field-effect transistor, allowing membrane
      potential to control the gain in mitogenic signaling circuits. 

PMID- 26293965
TI  - TRANSCRIPTION. Allosteric transcriptional regulation via changes in the overall
      topology of the core promoter.
AB  - Many transcriptional activators act at a distance from core promoter elements and
      work by recruiting RNA polymerase through protein-protein interactions. We show
      here how the prokaryotic regulatory protein CueR both represses and activates
      transcription by differentially modulating local DNA structure within the
      promoter. Structural studies reveal that the repressor state slightly bends the
      promoter DNA, precluding optimal RNA polymerase-promoter recognition. Upon
      binding a metal ion in the allosteric site, CueR switches into an activator
      conformation. It maintains all protein-DNA contacts but introduces torsional
      stresses that kink and undertwist the promoter, stabilizing an A-form DNA-like
      conformation. These factors switch on and off transcription by exerting dynamic
      control of DNA stereochemistry, reshaping the core promoter and making it a
      better or worse substrate for polymerase. 

PMID- 26293967
TI  - A risk worth taking.

PMID- 26293966
TI  - TRANSCRIPTION. Structures of the RNA polymerase-sigma54 reveal new and conserved
      regulatory strategies.
AB  - Transcription by RNA polymerase (RNAP) in bacteria requires specific promoter
      recognition by sigma factors. The major variant sigma factor (sigma(54))
      initially forms a transcriptionally silent complex requiring specialized
      adenosine triphosphate-dependent activators for initiation. Our crystal structure
      of the 450-kilodalton RNAP-sigma(54) holoenzyme at 3.8 angstroms reveals
      molecular details of sigma(54) and its interactions with RNAP. The structure
      explains how sigma(54) targets different regions in RNAP to exert its inhibitory
      function. Although sigma(54) and the major sigma factor, sigma(70), have similar
      functional domains and contact similar regions of RNAP, unanticipated differences
      are observed in their domain arrangement and interactions with RNAP, explaining
      their distinct properties. Furthermore, we observe evolutionarily conserved
      regulatory hotspots in RNAPs that can be targeted by a diverse range of
      mechanisms to fine tune transcription. 

PMID- 26293968
TI  - Silver(I)-Catalyzed Dearomatization of Alkyne-Tethered Indoles: Divergent
      Synthesis of Spirocyclic Indolenines and Carbazoles.
AB  - A high-yielding, divergent approach to generate either spirocyclic indolenines or
      carbazoles from a common indole-tethered propargyl alcohol precursor is
      described, with mechanistic insight provided. Either product can be obtained upon
      treatment with different Ag(I) catalysts at rt. An unexpected hydration reaction
      to afford (+/-)-actinopolymorphol B is also reported. 

PMID- 26293969
TI  - The effect of spectral filters on VEP and alpha-wave responses.
AB  - PURPOSE: Spectral filters are used to treat light sensitivity in individuals with
      traumatic brain injury (TBI); however, the effect of these filters on normal
      visual function has not been elucidated. Thus, the current study aimed to
      determine the effect of spectral filters on objectively-measured visual-evoked
      potential (VEP) and alpha-wave responses in the visually-normal population.
      METHODS: The full-field (15 degrees H*17 degrees V), pattern-reversal VEP (20'
      check size, mean luminance 52cd/m(2)) was administered to 20 visually-normal
      individuals. They were tested with four Intuitive-Colorimeter-derived, broad
      band, spectral filters (i.e., gray/neutral density, blue, yellow, and red), which
      produced similar luminance values for the test stimulus. The VEP N75 and P100
      latencies, and VEP amplitude, were recorded. Power spectrum analysis was used to
      derive the respective powers at each frequency, and peak frequency, for the
      selected 9-11Hz components of the alpha band. RESULTS: Both N75 and P100
      latencies increased with the addition of each filter when compared to baseline.
      Additionally, each filter numerically reduced intra-session amplitude variability
      relative to baseline. There were no significant effects on either the mean VEP
      amplitude or alpha wave parameters. CONCLUSIONS: The Intuitive Colorimeter
      filters significantly increased both N75 and P100 latencies, an effect which is
      primarily attributable (~75%) to luminance, and in some cases, specific spectral
      effects (e.g., blue and red). VEP amplitude and alpha power were not
      significantly affected. These findings provide an important reference to which
      either amplitude or power changes in light-sensitive, younger clinical groups can
      be compared.

PMID- 26293970
TI  - Ictal onset on intracranial EEG: Do we know it when we see it? State of the
      evidence.
AB  - OBJECTIVE: A major limitation of intracranial electroencephalography (iEEG) is
      recording from a confined region. This may falsely localize seizure onset if the
      distinction between ictal onset zone, proximity, and spread is unclear, or if the
      ictal rhythm is not clearly identified. Delineation of the ictal onset zone is
      crucial for surgical success. We appraised the evidence to determine whether
      specific iEEG ictal patterns are associated with the ictal onset zone. METHODS:
      We searched Embase for articles in English until September 30, 2014, with MeSH
      keywords related to intracranially implanted electrodes and seizures. Two authors
      independently screened abstracts, reviewed full text articles, and abstracted
      data. The association between seizure outcome and type of ictal onset pattern
      (IOP), and its extent, location, and spread were explored visually or by
      univariate analysis when sufficient data were provided. Methodologic quality of
      each study was assessed. RESULTS: We reviewed 1,987 abstracts from which 21
      articles were analyzed. Fifteen IOPs were reported. Low frequency high amplitude
      repetitive spiking (LFRS) was the most frequently reported IOP by studies that
      dealt with mesial temporal lobe epilepsy (mTLE) and investigated with depth
      electrodes. In neocortical epilepsy, low voltage fast activity (LVFA) was the
      most commonly described IOP. Delta activity was an infrequently reported IOP and
      was described mostly as a spread pattern. SIGNIFICANCE: LFRS is associated with
      good surgical outcome in mTLE and has a strong relation with mesial temporal
      pathology and its severity. LVFA is associated with neocortical temporal epilepsy
      and focal LVFA is associated with better surgical outcome. Electrodecrement may
      be associated with regional or widespread onsets. Rhythmic delta is a propagation
      rhythm rather than an IOP. Focal IOPs and slower propagation times are associated
      with better outcomes. The quality of the studies is suboptimal and there are
      methodological problems. Interobserver agreement is poorly documented.

PMID- 26293971
TI  - Synthesis and Screening of Human Monoamine Oxidase-A Inhibitor Effect of New 2
      Pyrazoline and Hydrazone Derivatives.
AB  - A group of 3,5-diaryl-2-pyrazoline and hydrazone derivatives was prepared via the
      reaction of various chalcones with hydrazide compounds in ethanol. Twenty
      original compounds were synthesized. Ten of these original compounds have a
      pyrazoline structure, nine of these original compounds have a hydrazone
      structure, and one of these original compounds has a chalcone structure.
      Structural elucidation of the compounds was performed by IR, (1)H NMR, (13)C NMR,
      mass spectral data, and elemental analyses. These compounds were tested for their
      inhibitory activities toward the A and B isoforms of human monoamine oxidase
      (MAO). Except for 3k and 6c, all compounds were found to be competitive,
      reversible, and selective inhibitors for either one of the isoforms (hMAO-A or
      MAO-B). Compounds 3k and 6c were found to be competitive, reversible, but non
      selective MAO inhibitors. Compound 6h showed hMAO-B inhibitory activity whereas
      the others potently inhibited hMAO-A. Compound 5c showed higher selectivity than
      the standard drug moclobemide. According to the experimental K(i) values,
      compounds 6i, 6d, and 6a exhibited the highest inhibitory activity toward hMAO-A.
      The AutoDock 4.2 program was employed to perform automated molecular docking. The
      calculated results obtained computationally were in good agreement with the
      experimental values.

PMID- 26293972
TI  - Radiological Evaluation and Endovascular Treatment of Hemoptysis.
AB  - Hemoptysis can be a life-threatening condition that warrants urgent investigation
      and intervention. Common causes include bronchiectasis, chronic obstructive
      pulmonary disease, tuberculosis, and malignancy. Computed tomography angiography
      is an accurate imaging modality for assessment of hemoptysis. The bronchial
      arteries are the source of bleeding in most cases of hemoptysis, and bronchial
      artery embolization is the treatment of choice. The aim of this article is to
      summarize the pathophysiology, causes, initial management, and diagnostic
      approach of hemoptysis. Endovascular treatment of hemoptysis, technique, embolic
      materials, outcomes, complications, and follow-up of patients are discussed. 

PMID- 26293973
TI  - Metastatic Disease to the Breast From Extramammary Malignancies: A Multimodality
      Pictorial Review.
AB  - This pictorial review demonstrates imaging features of extramammary malignancies
      metastatic to the breast seen with multiple modalities, including mammography,
      ultrasound, computed tomography (CT), positron emission tomography, and magnetic
      resonance imaging. Although rare, metastases to the breast may have a distinct
      imaging appearance from the appearance of primary breast cancers. They are
      important to identify because they can mimic benign breast disease and their
      treatment differs from that of primary breast cancer. Metastatic disease to the
      breast most commonly appears as a single round or oval mass with circumscribed
      margins. Sonographically it is usually hypoechoic, and with CT or magnetic
      resonance imaging it usually enhances. In contrast with primary breast cancer,
      breast metastases do not demonstrate spiculated margins and rarely have
      associated calcifications. A variety of clinical presentations of breast
      metastases are reviewed, including presentation with a palpable mass, detection
      at screening mammography, and detection with CT or positron emission tomography. 

PMID- 26293974
TI  - Effects of combined oleic acid and fluoride at sub-MIC levels on EPS formation
      and viability of Streptococcus mutans UA159 biofilms.
AB  - Despite the widespread use of fluoride, dental caries, a biofilm-related disease,
      remains an important health problem. This study investigated whether oleic acid,
      a monounsaturated fatty acid, can enhance the effect of fluoride on extracellular
      polysaccharide (EPS) formation by Streptococcus mutans UA159 biofilms at sub
      minimum inhibitory concentration levels, via microbiological and biochemical
      methods, confocal fluorescence microscopy, and real-time PCR. The combination of
      oleic acid with fluoride inhibited EPS formation more strongly than did fluoride
      or oleic acid alone. The superior inhibition of EPS formation was due to the
      combination of the inhibitory effects of oleic acid and fluoride against
      glucosyltransferases (GTFs) and GTF-related gene (gtfB, gtfC, and gtfD)
      expression, respectively. In addition, the combination of oleic acid with
      fluoride altered the bacterial biovolume of the biofilms without bactericidal
      activity. These results suggest that oleic acid may be useful for enhancing
      fluoride inhibition of EPS formation by S. mutans biofilms, without killing the
      bacterium. 

PMID- 26293975
TI  - Broadband silicon optical modulator using a graphene-integrated hybrid plasmonic
      waveguide.
AB  - Graphene is an excellent electronic and photonic material for developing
      electronic-photonic integrated circuits in Si-based semiconductor devices with
      ultra wide operational bandwidth. As an extended application, here we propose a
      broadband silicon optical modulator using a graphene-integrated hybrid plasmonic
      waveguide, and investigate the optical characteristics numerically at a
      wavelength of 1.55 MUm. The optical device is based on the surface plasmon
      polariton absorption of graphene. By electrically tuning the graphene's
      refractive index as low as that of a noble metal, the hybrid plasmonic waveguide
      supports a strongly confined highly lossy hybrid long-range surface plasmon
      polariton strip mode, and hence light coupled from an input waveguide experiences
      significant power attenuation as it propagates along the waveguide. Over the
      entire C-band from 1.530 to 1.565 MUm wavelengths, the on/off extinction ratio is
      larger than 13.7 dB. This modulator has the potential to play a key role in
      realizing graphene-Si waveguide-based integrated photonic devices. 

PMID- 26293976
TI  - Prospective study of telomere length and LINE-1 methylation in peripheral blood
      cells: the role of B vitamins supplementation.
AB  - PURPOSE: Deficiencies of folate, vitamins B12 and D are common age-related
      conditions. Vitamin B12 and folate are necessary for DNA methylation. Telomeres
      appear to be regulated by DNA methylation. Here, we study the effect of B
      vitamins supplementation on telomere length and global DNA methylation in a
      prospective study. METHODS: In total, 60 elderly subjects were supplemented for 1
      year with either vitamin B12, B6, folate, vitamin D and calcium (group A n = 31)
      or only vitamin D and calcium (group B n = 29). LINE-1 methylation, relative
      telomere length (T/S), vitamin B12, folate, homocysteine (tHcy) , 5
      methyltetrahydrofolate (5-methylTHF), S-adenosylhomocysteine (SAH), S
      adenosylmethionine (SAM), cystathionine and vitamin D were quantified before and
      after supplementation. RESULTS: At baseline, tHcy was high, vitamin D was low,
      and T/S did not differ between groups A and B. Vitamin supplementation increased
      LINE-1 methylation in group A at site 317 but reduced LINE-1 methylation in group
      B at site 327. There was no correlation between T/S and LINE-1 methylation at
      baseline. Multiple backward regression analysis revealed baseline tHcy and 5
      methylTHF are significant predictors of T/S. After supplementation in group B but
      not in group A, LINE-1 methylation correlated inversely with T/S, and LINE-1
      methylation variation was an independent predictor of T/S variation. B vitamins
      decreased tHcy significantly in group A. Multiple backward regression analysis
      showed 5-methylTHF in group A and tHcy in group B were significant predictors for
      LINE-1 methylation. At baseline, the lower LINE-1 methylation observed in
      subjects with 5-methylTHF >10 nmol/l was in agreement with a reduced methyl group
      transfer due to a lower SAM formation. In group B, an increase in telomere length
      was correlated with lower LINE-1 methylation. Subjects with hyperhomocysteinemia
      >12 umol/L had compared to those with normal tHcy a reduced LINE-1 methylation
      accompanied by a higher SAM and SAH (that inhibits demethylation of SAM) as well
      as lower 5-methylTHF. Additionally, subjects with tHcy > 12 umol/L had longer
      telomeres when compared with subjects having tHcy < 12 umol/L. CONCLUSIONS: The
      results suggest a possible effect of B vitamins for telomere biology in blood
      cells. Suboptimal B vitamins status and hyperhomocysteinemia are associated with
      altered DNA methylation and telomere length. These data have to be confirmed in
      future studies.

PMID- 26293978
TI  - Host homeostatic responses to alcohol-induced cellular stress in animal models of
      alcoholic liver disease.
AB  - Humans develop various clinical phenotypes of severe alcoholic liver disease,
      including alcoholic hepatitis and cirrhosis, generally after decades of heavy
      drinking. In such individuals, following each episode of drinking, their livers
      experience heightened intracellular and extracellular stresses that are closely
      associated with alcohol consumption and alcohol metabolism. This article focuses
      on the latest advances made in animal models on evolutionarily conserved
      homeostatic mechanisms for coping with and resolving these stress conditions. The
      mechanisms discussed include the stress-activated protein kinase JNK, energy
      regulator AMPK, autophagy and the inflammatory response. Over time, the host may
      respond variably to stress with protective mechanisms that are critical in
      determining an individual's vulnerability to developing severe alcoholic liver
      disease. A systematic review of these mechanisms and their temporal changes in
      animal models provides the basis for general conclusions, and raises questions
      for future studies. The relevance of these data to human conditions is also
      discussed.

PMID- 26293977
TI  - Validation of the FSA nutrient profiling system dietary index in French adults
      findings from SUVIMAX study.
AB  - PURPOSE: Population-wide nutritional recommendations give guidance on food
      groups' consumption, though a wide variability in nutritional quality within
      groups may subsist. Nutrient profiling systems may help capturing such
      variability. We aimed to apply and validate a dietary index based on the British
      Food Standards Agency nutrient profiling system (FSA-NPS DI) in French middle
      aged adults. METHODS: Dietary data were collected through repeated 24-h dietary
      records in participants of the Supplementation en Vitamines et Mineraux
      Antioxydants study (N = 5882). An aggregated dietary index at the individual
      level was computed using the FSA-NPS for each food consumed as well as compliance
      to the French nutritional guidelines using the Programme National Nutrition Sante
      Guideline Score (PNNS-GS). Cross-sectional associations between FSA-NPS DI and
      nutrient intake, PNNS-GS, socio-demographic factors, lifestyle and nutritional
      biomarkers were computed using ANOVAs. RESULTS: The FSA-NPS DI was able to
      characterize the quality of the diets at the individual level in terms of
      nutrient intake and of adherence to nutritional recommendations: +37.6 % in beta
      carotene intakes between subjects with a healthier diet versus subjects with a
      poorer diet, +42.8 % in vitamin C intakes; +17 % in PNNS-GS, all P < 0.001. FSA
      NPS-DI was also associated with nutritional status at the biological level: +21.4
      % in beta-carotene levels between subjects with a healthier diet versus subjects
      with a poorer diet, +12.8 % in vitamin C levels, all P < 0.001. CONCLUSIONS: The
      FSA-NPS DI is a useful and validated tool to discriminate individuals according
      to the quality of the diet, accounting for nutritional quality within food
      groups. Taking into account nutritional quality of individual foods allows
      monitoring change in dietary patterns beyond food groups.

PMID- 26293979
TI  - Portal hypertensive gastropathy with a focus on management.
AB  - Portal hypertensive gastropathy (PHG) is a painless condition of gastric mucosal
      ectasia and impaired mucosal defense, commonly seen in patients with elevated
      portal pressures. While it is typically asymptomatic and incidentally discovered
      on upper endoscopy, acute and chronic bleeding may occur. There are no definitive
      recommendations for treatment of asymptomatic PHG. Non-selective beta-blockers
      represent the mainstay of therapy for chronic bleeding, while somatostatin and
      vasopressin and their derivatives may be used in conjunction with supportive
      measures for acute bleeding. Salvage therapy with transjugular intrahepatic
      portosystemic shunt or rarely surgical shunt is appropriate when medical
      management fails. The role of endoscopic therapy for PHG is controversial. Liver
      transplantation should be considered as a final resort in cases of refractory
      bleeding due to PHG. 

PMID- 26293983
TI  - [Erectile dysfunction, PDE5A inhibitors and melanoma].

PMID- 26293982
TI  - Atomic View of Filament Growth in Electrochemical Memristive Elements.
AB  - Memristive devices, with a fusion of memory and logic functions, provide good
      opportunities for configuring new concepts computing. However, progress towards
      paradigm evolution has been delayed due to the limited understanding of the
      underlying operating mechanism. The stochastic nature and fast growth of
      localized conductive filament bring difficulties to capture the detailed
      information on its growth kinetics. In this work, refined programming scheme with
      real-time current regulation was proposed to study the detailed information on
      the filament growth. By such, discrete tunneling and quantized conduction were
      observed. The filament was found to grow with a unit length, matching with the
      hopping conduction of Cu ions between interstitial sites of HfO2 lattice. The
      physical nature of the formed filament was characterized by high resolution
      transmission electron microscopy. Copper rich conical filament with decreasing
      concentration from center to edge was identified. Based on these results, a clear
      picture of filament growth from atomic view could be drawn to account for the
      resistance modulation of oxide electrolyte based electrochemical memristive
      elements. 

PMID- 26293981
TI  - The effectiveness of dentifrices without and with sodium lauryl sulfate on
      plaque, gingivitis and gingival abrasion--a randomized clinical trial.
AB  - OBJECTIVES: The aim of this study was to compare the efficacy of a dentifrice
      without sodium lauryl sulfate (SLS) to a dentifrice with SLS in young adults aged
      18-34 years on gingivitis. MATERIAL AND METHODS: One hundred twenty participants
      (non-dental students) with a moderate gingival inflammation (bleeding on probing
      at 40-70 % of test sites) were included in this randomized controlled double
      blind clinical trial. According to randomization, participants had to brush their
      teeth either with dentifrice without SLS or with SLS for 8 weeks. The primary
      outcome was bleeding on marginal probing (BOMP). The secondary outcomes were
      plaque scores and gingival abrasion scores (GA) as well as a visual analogue
      scale (VAS) score at exit survey. Baseline and end differences were analysed by
      univariate analysis of covariance (ANCOVA) test, between group differences by
      independent t test and within groups by paired sample t test. RESULTS: BOMP
      improved within groups from on average 0.80 at baseline to 0.60 in the group
      without SLS and to 0.56 in the group with SLS. No statistical difference for
      BOMP, plaque and gingival abrasion was found between both groups. VAS scores for
      taste, freshness and foaming effect were significantly in favour of the SLS
      containing dentifrice. CONCLUSION: The test dentifrice without SLS was as
      effective as a regular SLS dentifrice on gingival bleeding scores and plaque
      scores. There was no significant difference in the incidence of gingival
      abrasion. CLINICAL RELEVANCE: In patients diagnosed with gingivitis, a dentifrice
      without SLS seems to be equally effective compared to a dentifrice with SLS and
      did not demonstrate any significant difference in gingival abrasion. In patient
      with recurrent aphthous ulcers, the absence of SLS may even be beneficial.
      However, participants indicate that they appreciate the foaming effect of a
      dentifrice with SLS more.

PMID- 26293980
TI  - Fibroblast growth factor receptor signaling in kidney and lower urinary tract
      development.
AB  - Fibroblast growth factor receptors (FGFRs) and FGF ligands are highly expressed
      in the developing kidney and lower urinary tract. Several classic studies showed
      many effects of exogenous FGF ligands on embryonic renal tissues in vitro and in
      vivo. Another older landmark publication showed that mice with a dominant
      negative Fgfr fragment had severe renal dysplasia. Together, these studies
      revealed the importance of FGFR signaling in kidney and lower urinary tract
      development. With the advent of modern gene targeting techniques, including
      conditional knockout approaches, several publications have revealed critical
      roles for FGFR signaling in many lineages of the kidney and lower urinary tract
      at different stages of development. FGFR signaling has been shown to be critical
      for early metanephric mesenchymal patterning, Wolffian duct patterning including
      induction of the ureteric bud, ureteric bud branching morphogenesis, nephron
      progenitor survival and nephrogenesis, and bladder mesenchyme patterning. FGFRs
      pattern these tissues by interacting with many other growth factor signaling
      pathways. Moreover, the many genetic Fgfr and Fgf animal models have structural
      defects mimicking numerous congenital anomalies of the kidney and urinary tract
      seen in humans. Finally, many studies have shown how FGFR signaling is critical
      for kidney and lower urinary tract patterning in humans.

PMID- 26293984
TI  - Egg intake and cancers of the breast, ovary and prostate: a dose-response meta
      analysis of prospective observational studies.
AB  - Evidence suggests that egg intake may be implicated in the aetiology of sex
      hormone-related cancers. However, dose-response relationships between egg intake
      and such cancers are unclear. Thus, we conducted a dose-response meta-analysis to
      summarise the dose-response relationships between egg consumption and the risk of
      breast, prostate and gynaecological cancers. A literature search was performed
      using PubMed and Embase up to April 2015 to identify relevant prospective
      observational studies. Summary relative risk (RR) and 95% CI were estimated using
      a random-effects model. For breast cancer, the linear dose-response meta-analysis
      found a non-significantly increased risk (RR for an increase of 5 eggs
      consumed/week: 1.05, 95% CI 0.99, 1.11, n 16,023 cases). Evidence for non
      linearity was not statistically significant (P non-linearity= 0.50, n 15,415
      cases) but consuming >= 5 eggs/week was significantly associated with an
      increased risk of breast cancer compared with no egg consumption, with the
      summary RR being 1.04 (95% CI 1.01, 1.07) for consuming 5 eggs/week and 1.09 (95%
      CI 1.03, 1.15) for consuming about 9 eggs/week. For other cancers investigated,
      the summary RR for an increase of 5 eggs consumed/week was 1.09 (95% CI 0.96,
      1.24, n 2636 cases) for ovarian cancer; 1.47 (95% CI 1.01, 2.14, n 609 cases) for
      fatal prostate cancer, with evidence of small-study effects (P Egger= 0.04). No
      evidence was found for an association with the risk of total prostate cancer.
      While our conclusion was tempered by the potential for publication bias and
      confounding, high egg intake may be associated with a modestly elevated risk of
      breast cancer, and a positive association between egg intake and ovarian and
      fatal prostate cancers cannot be ruled out.

PMID- 26293985
TI  - Erratum to: Concept Analysis: Health-Promoting Behaviors Related to Human
      Papilloma Virus Infection.
AB  - The article to which this erratum refers was published in Nursing Forum. 50:75
      82, 2015 (10.1111/nuf.12094)The authors regret to report that two co-authors
      names were missing in the final published version of this paper. The complete
      authors and their affiliations for this paper are follows:Tonna McCutcheon, APRN
      BC, Gina Schaar, DNP, RN, and Karen L. Parker, RN, PhD.Tonna McCutcheon, APRN-BC,
      is DNP student at the University of Southern Indiana; Gina Schaar, DNP, RN, is
      Assistant Professor at the College of Nursing and Health Professions, University
      of Southern Indiana; and Karen L. Parker, RN, PhD, is with College of Nursing and
      Health Professions, University of Southern Indiana, IN.

PMID- 26293986
TI  - A Van Der Waals Homojunction: Ideal p-n Diode Behavior in MoSe2.
AB  - A MoSe2 p-n diode with a van der Waals homojunction is demonstrated by stacking
      undoped (n-type) and Nb-doped (p-type) semiconducting MoSe2 synthesized by
      chemical vapor transport for Nb substitutional doping. The p-n diode reveals an
      ideality factor of ~1.0 and a high external quantum efficiency (~52%), which
      increases in response to light intensity due to the negligible recombination rate
      at the clean homojunction interface. 

PMID- 26293987
TI  - Imaging Fibrosis and Separating Collagens using Second Harmonic Generation and
      Phasor Approach to Fluorescence Lifetime Imaging.
AB  - In this paper we have used second harmonic generation (SHG) and phasor approach
      to auto fluorescence lifetime imaging (FLIM) to obtain fingerprints of different
      collagens and then used these fingerprints to observe bone marrow fibrosis in the
      mouse femur. This is a label free approach towards fast automatable detection of
      fibrosis in tissue samples. FLIM has previously been used as a method of contrast
      in different tissues and in this paper phasor approach to FLIM is used to
      separate collagen I from collagen III, the markers of fibrosis, the largest
      groups of disorders that are often without any effective therapy. Often
      characterized by an increase in collagen content of the corresponding tissue, the
      samples are usually visualized by histochemical staining, which is pathologist
      dependent and cannot be automated. 

PMID- 26293988
TI  - Factors associated with avoidable hospitalisation of children younger than 2
      years old: the 2006 Brazilian National Demographic Health Survey.
AB  - INTRODUCTION: Ambulatory Care Sensitive Conditions (ACSC) are conditions for
      which hospitalisation is thought to be avoidable with the use of effective
      preventive care and early disease management. The objective of this study was to
      estimate the rate of avoidable hospitalisations in children younger than 24
      months of age participating in a Brazilian national representative survey and to
      identify the risk factors for such hospitalisations. METHODS: We analysed data
      from a cross-sectional study of 1901 children from the 2006 Brazilian National
      Demographic Health Survey of Women and Children (NDHS). The children's
      socioeconomic, biological and maternal characteristics, nutritional status, and
      access to healthcare were tested; variables with p < 0.20 were selected to fit a
      Poisson regression. RESULTS: The prevalence of avoidable hospitalisation was
      11.8% (95% Confidence Interval [CI], 9.0, 15.2); the prevalence was higher in the
      Southeast (40.1%) and Northwest (21.7%) macro-regions. The multivariate model
      identified five risk factors for avoidable hospitalisation: male gender
      (Prevalence Ratio [PR] = 1.48, p = 0.004), low socioeconomic level (PR = 1.51, p
      = 0.005), children from mothers younger than 20 years of age (PR = 1.41, p =
      0.031), not breastfed within the first hour of life (PR = 1.29, p = 0.034), and
      neonatal hospitalisation (PR = 1.66, p = 0.043). CONCLUSIONS: To decrease the
      costs associated with avoidable hospitalisations, health managers and
      professionals should focus their efforts on providing effective primary
      healthcare to families of low socioeconomic levels, particularly prenatal and
      paediatric care, as well as encouraging breastfeeding and supporting young
      mothers. Strategies to improve children's health by controlling such
      hospitalisations in Brazil should consider all residence areas and geopolitical
      macro-regions.

PMID- 26293989
TI  - Hemoglobinopathies and Leg Ulcers.
AB  - Major hemoglobinopathies, including sickle cell anemia, are becoming a global
      health issue. Leg ulcers are the most common cutaneous manifestation of sickle
      cell disease and an important contributor to morbidity burden in this population.
      Leg ulcers following sickling disorders are extremely painful, and hard to heal.
      The clinical evidence for the optimal management of these ulcers is limited.
      Treating the cause and the strategies to prevent sickling are the mainstay of
      treatment. The basic principles of wound bed preparation and compression therapy
      is beneficial in these patients. 

PMID- 26293990
TI  - [Is it a matter of habit?].

PMID- 26293991
TI  - Behavioural phenotypes in translation.

PMID- 26293994
TI  - Bochdalek Congenital Diaphragmatic Hernia in an Adult Sheep.
AB  - Congenital diaphragmatic hernia (CDH) is a rare condition. The aetiology of CDH
      is often unclear. In our case, a hollow mass was noted on MRI. Cardiac ejection
      fraction was diminished (47.0%) compared to 60.5% (average of 10 other normal
      animals, P < 0.05). The final diagnosis of congenital diaphragmatic hernia
      (Bochdalek type) was made when the sheep underwent surgery. The hernia was right
      sided and contained the abomasum. Lung biopsy demonstrated incomplete development
      with a low number of bronchopulmonary segments and vessels. The likely cause of
      this hernia was genetic malformation. 

PMID- 26293995
TI  - Does Anterior Fat Pad Removal Reduce the Incidence of Atrial Fibrillation after
      CABG? A Meta-Analysis of Randomized Controlled Trials.
AB  - BACKGROUND: Atrial fibrillation (AF) is a common complication after coronary
      artery bypass grafting (CABG). Several prospective randomized controlled trials
      (RCTs) have evaluated the effect of intact and removed anterior fat pads on the
      incidence of AF after CABG with conflicting results. We collected these RCTs and
      conducted a meta-analysis to determine whether anterior fat pad removal is
      effective in preventing the new onset of AF after CABG. METHODS AND RESULTS:
      Prospective RCTs were collected for analysis and the main outcomes include the
      occurrence of AF after CABG, total hospital stay, and major complications.
      Statistical analysis was conducted using RevMan 5.0.18 software (The Cochrane
      Collaboration), and pooled estimates of the effect were reported as risk ratios
      (RRs) or mean differences (MDs) with their 95% confidence intervals (CIs). The
      results of this meta-analysis indicate that anterior fat pad removal was not
      associated with a decreased risk of occurrence of AF after CABG (RR = 1.34, 95%
      CI: 0.88-2.03; P = 0.18), and it also did not increase the risk of major
      complications (RR = 1.05, 95% CI: 0.75-1.47; P = 0.79) or lengthen total hospital
      stay (MD = 0.06, 95% CI: -0.46 to 0.58; P = 0.83) compared with the control
      group. CONCLUSION: Anterior fat pad removal did not decrease the risk of the
      occurrence of AF after CABG despite its safety and convenience, and it should not
      be used to prevent new-onset AF after CABG unless new evidence is provided.

PMID- 26293997
TI  - Bronchodilators, receptors and cross-talk: Together is better?
AB  - The most widely used maintenance therapies in chronic obstructive pulmonary
      disease (COPD) are long-acting muscarinic antagonists (LAMAs), and a number of
      these drugs are now available in combination with long-acting beta2-agonists
      (LABAs). LAMAs inhibit the parasympathetic muscarinic pathway, while LABAs, as
      sympathomimetics, reduce airway smooth muscle (ASM) tone. As well as directly
      controlling the constriction and relaxation of ASM, muscarinic and adrenergic
      receptors are found on inflammatory cells, and drugs that target these receptors
      may also reduce inflammation in COPD. Evidence suggests that the muscarinic and
      adrenergic pathways cross-talk at the level of neuronal input to the ASM via
      second-messenger pathways within ASM cells. Although the cross-talk is not
      completely understood, pharmacologically targeting both pathways in COPD can
      maximize bronchodilation. Combining LAMAs and LABAs demonstrated improved
      efficacy compared with the individual therapies and so, for greater convenience,
      several fixed-dose combinations for once-daily use have been developed. These
      fixed-dose combinations demonstrate improvements in both lung-function and
      patient-reported outcomes compared with well-established monotherapies, with
      similar tolerability profiles to the individual agents. 

PMID- 26293996
TI  - Downregulated Poly-C binding protein-1 is a novel predictor associated with poor
      prognosis in Acute Myeloid Leukemia.
AB  - BACKGROUND: Depletion of Poly-C binding protein-1(PCBP1) is implicated in various
      human malignancies. However, the underlying biological effect of PCBP1 in
      cancers, including acute myeloid leukemia (AML), still remains elusive. The
      purpose of this study was to examine the expression and clinical outcome of
      PCBP1in acute myeloid leukemia. METHODS: Bone marrow fluids of 88 newly diagnosed
      AML patients were sampled, and the PCBP1 mRNA expression level was evaluated
      using quantitative RT-PCR. The association between PCBP1 expression and
      clinicopathological features or the survival status of the patients was assessed
      by Chi-square test and Kaplan-Meier method. RESULTS: Comparing newly diagnosed
      AML patients to normal healthy donors, PCBP1 expression was significantly
      decreased in AML patients (P < 0.001). Conversely, PCBP1 expression had
      accordingly recovered back to normal in patients with complete remission (P <
      0.001). Clinical feature analyses showed that PCBP1 expression was negatively
      correlated with white blood cell count (P = 0.024). In addition, patients with
      low PCBP1 expression had poor disease-free survival (11.8% vs. 45.3%; P = 0.01)
      and overall survival (18.2% vs. 42.4%; P = 0.032), respectively. CONCLUSIONS:
      Taken together, our results showed for the first time that expression of PCBP1
      was down-regulated in newly diagnosed AML patients and might be an independent
      prognostic marker in AML and should to be further investigated.

PMID- 26293998
TI  - Staff experiences of caring for patients with extended-spectrum beta-lactamase
      producing bacteria: A qualitative study.
AB  - BACKGROUND: Patients who become carriers of antibiotic-resistant bacteria are
      sometimes stigmatized by health professionals. Staff members' fears of becoming
      infected could affect their willingness to care for these patients. METHODS: The
      purpose of this study was to increase the knowledge of what it means for staff in
      acute care settings and nursing homes to care for patients with extended-spectrum
      beta-lactamase (ESBL)-producing bacteria. Assistant nurses, registered nurses,
      and physicians from acute care settings and nursing homes were interviewed. A
      modified version of Grounded Theory was used for the analysis. RESULTS: The
      analysis resulted in the core category "to operate as an expert in a chaotic
      environment" in acute care settings. Despite a lack of resources, hospital staff
      try to provide the best possible care for patients with ESBL. The analysis of the
      interviews in the nursing homes resulted in the core category "the employee who,
      despite uncertainty, provides good care." Despite some fear, and a lack of
      knowledge, the study participants tried to provide the residents with good care.
      CONCLUSION: Staff in acute care settings and nursing homes must have adequate
      knowledge and reasonable working conditions to be able to provide high-quality
      care for patients and residents who are ESBL carriers.

PMID- 26293999
TI  - Do high-touch surfaces in public spaces pose a risk for influenza transmission? A
      virologic study during the peak of the 2009 influenza A(H1N1) pandemic in Geneva,
      Switzerland.

PMID- 26294000
TI  - Spatio-temporal impacts of dairy lagoon water reuse on soil: heavy metals and
      salinity.
AB  - Diminishing freshwater resources have brought attention to the reuse of degraded
      water as a water resource rather than a disposal problem. The spatial impact and
      sustainability of dairy lagoon water reuse from concentrated animal feeding
      operations (CAFOs) has not been evaluated at field scale. The objective of this
      study is to monitor the impact of dairy lagoon water blended with recycled water
      on a 32 ha field near San Jacinto, CA from 2007 to 2011. Spatial monitoring was
      based on soil samples collected at locations identified from apparent soil
      electrical conductivity (ECa) directed sampling. Soil samples were taken at depth
      increments of 0-0.15, 0.15-0.3, 0.3-0.6, 0.6-0.9, 0.9-1.2, 1.2-1.5, and 1.5-1.8 m
      at 28 sample sites on 7-11 May 2007 and again on 31 May - 2 June 2011 after 4
      years of irrigation with the blended waters. Chemical analyses included salinity
      (electrical conductivity of the saturation extract, ECe), pHe (pH of the
      saturation extract), SAR (sodium adsorption ratio), trace elements (As, B, Mo,
      Se), and heavy metals (Cd, Cu, Mn, Ni, Zn). Results indicate a decrease in mean
      values of pHe at all depth increments; a decrease in ECe and SAR above a depth of
      0.15 m, but an increase below 0.15 m; a decrease in all trace elements except B,
      which increased throughout the 1.8 m profile; and the accumulation of Cd, Mn, and
      Ni at all depth increments, while Cu was readily leached from the 1.8 m profile.
      Zinc showed little change. The results focused concern on the potential long-term
      agronomic effect of salinity, SAR, and B, and the long-term environmental threat
      of salinity and Cu to detrimentally impact groundwater. The accumulation of Cd,
      Mn, and Ni in the soil profile raised concern since it provided a potential
      future source of metals for leaching. The long-term sustainability of dairy
      lagoon water reuse hinges on regular monitoring to provide spatial feedback for
      site-specific management. 

PMID- 26294001
TI  - Periprosthetic fractures: concepts of biomechanical in vitro investigations.
AB  - PURPOSE: Experimental in vitro studies investigating periprosthetic fractures
      after joint replacement are used increasingly. The purpose of this review was to
      deliver a condensed survey of studies in order to provide researchers with an
      overview of relevant scientific results and their clinical relevance. METHODS: A
      literature search was conducted to obtain all available papers dealing with
      periprosthetic fractures, with particular attention being paid to articles with
      an experimental research design. Study goals, scientific methods and results,
      their interpretation and clinical relevance were assessed and compared. The main
      focus was on comparability with clinical fracture patterns and physiological
      joint loads. RESULTS: Excluding duplicates, 24 studies with regard to artificial
      hip, knee and shoulder joints were found dating back to August 2000. Almost all
      studies were performed quasi-statically and without consideration of muscle
      forces and thus reflect selected loading conditions and no dynamic situation
      during activities of daily living (ADL). Various experimental protocols were
      used, differing in the choice of experimental material, implant and fixation
      system and load application. CONCLUSIONS: In vitro studies regarding
      periprosthetic fracture research allow controlling for disturbances, such as
      clinically occurring risk factors like reduced bone mineral density (BMD) or
      greater patient age. Notwithstanding, due to methodological differences,
      comparisons between studies were possible to a limited degree only. For this
      reason, and because of quasi-static loading typically applied, results can only
      be partially applied to clinical practice.

PMID- 26294002
TI  - Fathers of orthopaedics in Germany (eighteenth and early nineteenth centuries):
      Lorenz Heister in Helmsted; Johann Friedrich Dieffenbach in Berlin; Heine and
      family in Wurzburg.
AB  - In orthopaedic medicine in Germany, Lorenz Heister, practicing in the eighteenth
      century, is considered one of the fathers of German surgery and is renowned for
      his books on management of hemorrhage, wounds, fractures, bandaging,
      instrumentation and surgery. After Heister, at the beginning of the nineteenth
      century, orthopaedic medicine in Germany developed uniformly. In a period when
      few doctors were interested in a separate discipline of orthopaedics, Germany led
      in this field. Heine devoted himself to the development of the new profession of
      orthopaedics, and in 1816, he opened the first orthopaedic institute on German
      soil in the former monastery of St. Stephen, which later became known as the
      Karolinen-Institut. Along with Heine and his family, the special development of
      orthopaedics in Berlin may be attributed to the work of Dieffenbach who, in 1832,
      became professor at the University of Berlin and in 1840 director of the Clinical
      Institute for Surgery at Charite Hospital. 

PMID- 26294003
TI  - Abnormalities in Plasma Phospholipid Fatty Acid Profiles of Patients with
      Hepatocellular Carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related
      death worldwide. In the present study, we aimed to profile the possible changes
      in plasma phospholipid fatty acid composition of HCC patients, and to identify
      the fatty acid biomarkers that could distinguish HCC patients from healthy
      controls. A total of 37 plasma samples from healthy controls and HCC patients
      were collected and their phospholipid fatty acid profiles were characterized by
      gas chromatography-mass spectrometry followed by multivariate statistical
      analysis. Twenty-five fatty acids were identified and quantified, their
      proportions varied greatly between two groups, suggesting each group has its own
      fatty acid pattern. Orthogonal partial least squares discriminant analysis in
      terms of fatty acid profiles showed that HCC patients could be clearly
      distinguished from healthy controls. More importantly, linoleic acid (18:2n-6),
      oleic acid (18:1n-9), arachidonic acid (20:4n-6) and palmitic acid (16:0) were
      identified as the potential fatty acid biomarkers of HCC patients. Additionally,
      to further identify the major cause of the abnormality of plasma fatty acid
      profile, fatty acid distributions of cancerous tissue and its surrounding tissue
      from 42 HCC patients were also examined. Due to have similar variation trend of
      major fatty acid biomarkers, linoleic acid (18:2n-6), oleic acid (18:1n-9),
      abnormalities in plasma phospholipid fatty acid profiles of HCC patients may be
      mainly attributed to the alternation of intrinsic fatty acid metabolism caused by
      cancer per se, but not to the differences in dietary factors.

PMID- 26294004
TI  - Evaluation of phosphate-solubilizing bacteria on the growth and grain yield of
      rice (Oryza sativa L.) cropped in northern Iran.
AB  - AIMS: This study aimed to evaluate the efficiency of four phosphate-solubilizing
      bacteria (PSB) on the growth and yield of rice under different soil conditions.
      METHODS: Bacterial strains were Rahnella aquatillis (KM977991), Enterobacter sp.
      (KM977992), Pseudomonas fluorescens and Pseudomonas putida. These studies were
      conducted on different rice cultivars ('Shiroodi', 'Tarom' and 'Tarom Hashemi')
      in both pot and field experiments. Measurements started from transplanting and
      continued throughout the growing season in field experiments. RESULTS: Single PSB
      inoculations in field trials increased grain yield, biological yield, total
      number of stems hill(-1) , number of panicles hill(-1) and plant height by 8.50
      26.9%, 12.4-30.9%, 20.3-38.7%, 22.1-36.1% and 0.85-3.35% in experiment 1, by 7.74
      14.7%, 4.22-12.6%, 6.67-16.7%, 4.0-15.4% and 3.15-4.20% in experiment 2 and by
      23.4-37%, 16.1-36.4%, 30.2-39.1%, 28.8-34% and 2.11-4.55% in experiment 3,
      respectively, compared to the control. Our results indicate that the application
      of triple super phosphate together with PSB inoculations resulted in reducing the
      use of chemical fertilizers (about 67%) and increasing fertilizer use efficiency.
      CONCLUSIONS: This study clearly indicates that these PSBs can be used as
      biofertilizers in ecological rice agricultural systems. SIGNIFICANCE AND IMPACT
      OF THE STUDY: To the best of our knowledge, this is first report on the
      association of Rahnella aquatilis with rice and also the application of a
      mathematical model to evaluate the effect of PSBs on rice growth.

PMID- 26294006
TI  - Corrigendum: Revealing the planar chemistry of two-dimensional heterostructures
      at the atomic level.

PMID- 26294005
TI  - Meta-analysis of modifiable risk factors for Alzheimer's disease.
AB  - BACKGROUND: The aetiology of Alzheimer's disease (AD) is believed to involve
      environmental exposure and genetic susceptibility. The aim of our present
      systematic review and meta-analysis was to roundly evaluate the association
      between AD and its modifiable risk factors. METHODS: We systematically searched
      PubMed and the Cochrane Database of Systematic Reviews from inception to July
      2014, and the references of retrieved relevant articles. We included prospective
      cohort studies and retrospective case-control studies. RESULTS: 16,906 articles
      were identified of which 323 with 93 factors met the inclusion criteria for meta
      analysis. Among factors with relatively strong evidence (pooled population >5000)
      in our meta-analysis, we found grade I evidence for 4 medical exposures
      (oestrogen, statin, antihypertensive medications and non-steroidal anti
      inflammatory drugs therapy) as well as 4 dietary exposures (folate, vitamin E/C
      and coffee) as protective factors of AD. We found grade I evidence showing that
      one biochemical exposure (hyperhomocysteine) and one psychological condition
      (depression) significantly increase risk of developing AD. We also found grade I
      evidence indicative of complex roles of pre-existing disease (frailty, carotid
      atherosclerosis, hypertension, low diastolic blood pressure, type 2 diabetes
      mellitus (Asian population) increasing risk whereas history of arthritis, heart
      disease, metabolic syndrome and cancer decreasing risk) and lifestyle (low
      education, high body mass index (BMI) in mid-life and low BMI increasing the risk
      whereas cognitive activity, current smoking (Western population), light-to
      moderate drinking, stress, high BMI in late-life decreasing the risk) in
      influencing AD risk. We identified no evidence suggestive of significant
      association with occupational exposures. CONCLUSIONS: Effective interventions in
      diet, medications, biochemical exposures, psychological condition, pre-existing
      disease and lifestyle may decrease new incidence of AD.

PMID- 26294007
TI  - In Vivo Measurement of Cervical Spinal Cord Deformation During Traumatic Spinal
      Cord Injury in a Rodent Model.
AB  - The spinal cord undergoes physical deformation during traumatic spinal cord
      injury (TSCI), which results in biological damage. This study demonstrates a
      novel approach, using magnetic resonance imaging and image registration
      techniques, to quantify the three-dimensional deformation of the cervical spinal
      cord in an in vivo rat model. Twenty-four male rats were subjected to one of two
      clinically relevant mechanisms of TSCI (i.e. contusion and dislocation) inside of
      a MR scanner using a novel apparatus, enabling imaging of the deformed spinal
      cords. The displacement fields demonstrated qualitative differences between
      injury mechanisms. Three-dimensional Lagrangian strain fields were calculated,
      and the results from the contusion injury mechanism were deemed most reliable.
      Strain field error was assessed using a Monte Carlo approach, which showed that
      simulated normal strain error experienced a bias, whereas shear strain error did
      not. In contusion injury, a large region of dorso-ventral compressive strain was
      observed under the impactor which extended into the ventral region of the spinal
      cord. High tensile lateral strains under the impactor and compressive lateral
      strains in the lateral white matter were also observed in contusion. The ability
      to directly observe and quantify in vivo spinal cord deformation informs our
      knowledge of the mechanics of TSCI. 

PMID- 26294008
TI  - A Well-Controlled Nucleus Pulposus Tissue Culture System with Injection Port for
      Evaluating Regenerative Therapies.
AB  - In vitro evaluation of nucleus pulposus (NP) tissue regeneration would be useful,
      but current systems for NP culture are not ideal for injections. The aim of this
      study was to develop a long-term culture system for NP tissue that allows
      injections of regenerative agents. Bovine caudal NPs were harvested and placed in
      the newly designed culture system. After equilibration of the tissue to 0.3 MPa
      the volume was fixed and the tissue was cultured for 28 days. The cell viability
      and extracellular matrix composition remained unchanged during the culture period
      and gene expression profiles were similar to those obtained in earlier studies.
      Furthermore, to test the responsiveness of bovine caudal NPs in the system,
      samples were cultured for 4 days and injected twice (day 1 and 3) with (1) PBS,
      (2) Link-N, for regeneration, and (3) TNF-alpha, for degeneration. It was shown
      that TNF-alpha increased COX2 gene expression, whereas no effect of Link-N was
      detected. In conclusion, the newly designed system allows long-term culture of NP
      tissue, wherein tissue reactions to injected stimulants can be observed.

PMID- 26294009
TI  - Fluid-Structure Interaction Model of a Percutaneous Aortic Valve: Comparison with
      an In Vitro Test and Feasibility Study in a Patient-Specific Case.
AB  - Transcatheter aortic valve replacement (TAVR) represents an established recent
      technology in a high risk patient base. To better understand TAVR performance, a
      fluid-structure interaction (FSI) model of a self-expandable transcatheter aortic
      valve was proposed. After an in vitro durability experiment was done to test the
      valve, the FSI model was built to reproduce the experimental test. Lastly, the
      FSI model was used to simulate the virtual implant and performance in a patient
      specific case. Results showed that the leaflet opening area during the cycle was
      similar to that of the in vitro test and the difference of the maximum leaflet
      opening between the two methodologies was of 0.42%. Furthermore, the FSI
      simulation quantified the pressure and velocity fields. The computed strain
      amplitudes in the stent frame showed that this distribution in the patient
      specific case is highly affected by the aortic root anatomy, suggesting that the
      in vitro tests that follow standards might not be representative of the real
      behavior of the percutaneous valve. The patient-specific case also compared in
      vivo literature data on fast opening and closing characteristics of the aortic
      valve during systolic ejection. FSI simulations represent useful tools in
      determining design errors or optimization potentials before the fabrication of
      aortic valve prototypes and the performance of tests. 

PMID- 26294011
TI  - Automotive shredder residue (ASR) management: An overview.
AB  - On the basis of statistical data, approximately 6.5 million tons of ELVs were
      produced in Europe in 2011. ELVs are processed according to a treatment scheme
      comprising three main phases: depollution, dismantling and shredding. The ferrous
      fraction represents about 70-75% of the total shredded output, while nonferrous
      metals represent about 5%. The remaining 20-25% is referred to as automotive
      shredder residue (ASR). ASR is largely landfilled due to its heterogeneous and
      complex matrix. With a start date of January 1st 2015, the European Directive
      2000/53/EC establishes the reuse and recovery of a minimum of 95% ELV total
      weight. To reach these targets various post-shredder technologies have been
      developed with the aim of improving recovery of materials and energy from ASR. In
      order to evaluate the environmental impacts of different management options of
      ELVs, the life cycle assessment (LCA) methodology has been applied taking into
      account the potential implication of sustainable design of vehicles and treatment
      of residues after shredding of ELVs. Findings obtained reveal that a combination
      of recycling and energy recovery is required to achieve European targets, with
      landfilling being viewed as the least preferred option. The aim of this work is
      to provide a general overview of the recent development of management of ELVs and
      treatment of ASR with a view to minimizing the amount of residues disposed of in
      landfill.

PMID- 26294010
TI  - Cellular and Nuclear Alignment Analysis for Determining Epithelial Cell
      Chirality.
AB  - Left-right (LR) asymmetry is a biologically conserved property in living
      organisms that can be observed in the asymmetrical arrangement of organs and
      tissues and in tissue morphogenesis, such as the directional looping of the
      gastrointestinal tract and heart. The expression of LR asymmetry in embryonic
      tissues can be appreciated in biased cell alignment. Previously an in vitro
      chirality assay was reported by patterning multiple cells on microscale defined
      geometries and quantified the cell phenotype-dependent LR asymmetry, or cell
      chirality. However, morphology and chirality of individual cells on
      micropatterned surfaces has not been well characterized. Here, a Python-based
      algorithm was developed to identify and quantify immunofluorescence stained
      individual epithelial cells on multicellular patterns. This approach not only
      produces results similar to the image intensity gradient-based method reported
      previously, but also can capture properties of single cells such as area and
      aspect ratio. We also found that cell nuclei exhibited biased alignment. Around
      35% cells were misaligned and were typically smaller and less elongated. This new
      imaging analysis approach is an effective tool for measuring single cell
      chirality inside multicellular structures and can potentially help unveil
      biophysical mechanisms underlying cellular chiral bias both in vitro and in vivo.

PMID- 26294012
TI  - Tourism and solid waste generation in Europe: A panel data assessment of the
      Environmental Kuznets Curve.
AB  - The relationship between tourism growth and municipal solid waste (MSW)
      generation has been, until now, the subject of little research. This is puzzling
      since the tourism sector is an important MSW generator and, at the same time, is
      willing to avoid negative impacts from MSW mismanagement. This paper aims to
      provide tools for tourism and MSW management by assessing the effects of tourism
      volume, tourism quality and tourism specialization on MSW generation in the UE.
      This is done using the Environmental Kuznets Curve (EKC) framework. The study
      considers a panel data for 32 European economies in the 1997-2010 periods.
      Empirical results support the EKC hypothesis for MSW and shows that northern
      countries tend to have lower income elasticity than less developed countries;
      furthermore, results confirm a non-linear and significant effect of tourism
      arrivals, expenditure per tourist and tourism specialization on MSW generation. 

PMID- 26294013
TI  - The quest for targeted therapy in fragile X syndrome.
AB  - Fragile X syndrome (FXS) is the most common, monogenetic cause of intellectual
      disability and autism-spectrum disorders. Although there is no effective therapy,
      greater understanding of disturbed neuronal pathways has introduced options for
      targeted therapy. But whereas many FXS phenotypes were improved in preclinical
      studies with drugs targeting these pathways in the FXS mouse model, attempts to
      translate these animal-model success stories into treatment of patients in
      clinical trials have been extremely disappointing. Complicating factors,
      particularly in animal studies, include mouse inbred strains, variability in
      functional studies between laboratories, publication bias and lack of reliable
      and objective primary outcome measures in both mice and patients. Possibly most
      important, however, is one factor that has been little explored: the complexity
      of the molecular imbalance in FXS and the need to simultaneously target several
      different disturbed pathways and different cellular compartments. New, well
      conceived animal studies should generate more productive approaches in the quest
      for targeted therapy for FXS. 

PMID- 26294014
TI  - Single-cell ATAC-seq: strength in numbers.
AB  - Single-cell ATAC-seq detects open chromatin in individual cells. Currently data
      are sparse, but combining information from many single cells can identify
      determinants of cell-to-cell chromatin variation. 

PMID- 26294016
TI  - Editorial overview: biotic interactions: the diverse and dynamic nature of
      perception and response in plant interactions: from cells to communities.

PMID- 26294015
TI  - Stem cell mobilization chemotherapy with gemcitabine is effective and safe in
      myeloma patients with bortezomib-induced neurotoxicity.
AB  - Vinorelbine chemotherapy with granulocyte-colony stimulating factor (G-CSF)
      stimulation is a widely applied non-myelosuppressive mobilization regimen in
      Switzerland for myeloma patients, but its neurotoxic potential limits its use in
      patients with bortezomib-induced polyneuropathy. In this single-center study, we
      alternatively evaluated safety and effectiveness of gemcitabine chemotherapy with
      G-CSF for mobilization of autologous stem cells. Between March 2012 and February
      2013, all bortezomib-pretreated myeloma patients planned to undergo first-line
      high-dose melphalan chemotherapy received a single dose of 1250 mg/m2
      gemcitabine, with G-CSF started on day 4. The 24 patients in this study had
      received a median of four cycles of bortezomib-dexamethason-based induction.
      Bortezomib-related polyneuropathy was identified in 21 patients (88%) by clinical
      evaluation and a standardized questionnaire. Administration of gemcitabine
      mobilization did not induce new or aggravate pre-existing neuropathy. Stem cell
      mobilization was successful in all 24 patients, with a single day of apheresis
      being sufficient in 19 patients (78%). The median yield was 9.51*10(6) CD34+
      cells/kg. Stem collection could be accomplished at day 8 in 67%. Our data suggest
      that single-dose gemcitabine together with G-CSF is an effective mobilization
      regimen in myeloma patients and a safe alternative non-myelosuppressive
      mobilization chemotherapy for myeloma patients with bortezomib-induced
      polyneuropathy.

PMID- 26294017
TI  - Prediction of subsequent miscarriage risk in women who present with a viable
      pregnancy at the first early pregnancy scan.
AB  - OBJECTIVES: To generate and evaluate a new prediction model for miscarriage in
      women who present with a viable intrauterine pregnancy (IUP) at the primary early
      pregnancy scan and to compare this new model to a previously published model.
      MATERIALS AND METHODS: Data were collected prospectively from women presenting to
      the early pregnancy unit with a viable IUP between November 2006 and January
      2013. More than 30 historical, clinical and ultrasonographic variables were
      recorded on a standardised datasheet at the first visit. Women were followed
      until the final outcome was known at the end of the first trimester: viable IUP
      or miscarriage. A new multinomial logistic regression model was developed
      retrospectively on training cases and tested prospectively on test cases. The
      performance of the new prediction model was evaluated using receiver operating
      characteristic (ROC) curves and compared to a previously published model. After
      removing cases with missing values for the model of Oates, the area under the ROC
      curve (AUC) was also calculated for the new model and the Oates model. RESULTS: A
      total of 1115 consecutive first-trimester women presented to the early pregnancy
      unit. Eight hundred and sixty-two women with a viable IUP at the first scan whose
      outcome was known at the end of the first trimester were included in the final
      analysis. Five hundred and sixty-six women were included in the training set and
      296 in the test set. 92.1% were viable and 7.9% had miscarried at the end of the
      first trimester. The most significant independent prognostic variables for the
      logistic regression model were as follows: maternal age, embryonic heart rate
      (EHR), logarithm [gestational sac (GS) volume/crown-rump length (CRL)], CRL and
      the presence or absence of clots per vagina (PV) at presentation. The performance
      of the new model compared with the Oates model gave an AUC of 0.870 vs 0.847 for
      the training set and 0.783 vs 0.744 for the test set. After removing cases with
      missing values for the model of Oates 2013, the performance of the new model
      compared to the Oates model gave an AUC of 0.887 vs 0.861 for the training set
      and 0.816 vs 0.734 for the test set (P-value <0.04). CONCLUSIONS: We have
      developed a new prediction model which indicates the likelihood of miscarriage.
      In women who present with a viable IUP at the primary scan, advancing maternal
      age in the presence of clots PV increases the probability of subsequent
      miscarriage. Whereas, in women with a higher EHR in the presence of an increased
      GS volume/CRL ratio, the likelihood of subsequent miscarriage is reduced. This
      new model outperforms the previously published model developed in our unit.

PMID- 26294018
TI  - Recognition deficits in mice carrying mutations of genes encoding BLOC-1 subunits
      pallidin or dysbindin.
AB  - Numerous studies have implicated DTNBP1, the gene encoding dystrobrevin-binding
      protein or dysbindin, as a candidate risk gene for schizophrenia, though this
      relationship remains somewhat controversial. Variation in dysbindin, and its
      location on chromosome 6p, has been associated with cognitive processes,
      including those relying on a complex system of glutamatergic and dopaminergic
      interactions. Dysbindin is one of the seven protein subunits that comprise the
      biogenesis of lysosome-related organelles complex 1 (BLOC-1). Dysbindin protein
      levels are lower in mice with null mutations in pallidin, another gene in the
      BLOC-1, and pallidin levels are lower in mice with null mutations in the
      dysbindin gene, suggesting that multiple subunit proteins must be present to form
      a functional oligomeric complex. Furthermore, pallidin and dysbindin have similar
      distribution patterns in a mouse and human brain. Here, we investigated whether
      the apparent correspondence of pallid and dysbindin at the level of gene
      expression is also found at the level of behavior. Hypothesizing a mutation
      leading to underexpression of either of these proteins should show similar
      phenotypic effects, we studied recognition memory in both strains using the novel
      object recognition task (NORT) and social novelty recognition task (SNRT). We
      found that mice with a null mutation in either gene are impaired on SNRT and NORT
      when compared with wild-type controls. These results support the conclusion that
      deficits consistent with recognition memory impairment, a cognitive function that
      is impaired in schizophrenia, result from either pallidin or dysbindin mutations,
      possibly through degradation of BLOC-1 expression and/or function. 

PMID- 26294035
TI  - Carbon dioxide level and form of soil nitrogen regulate assimilation of
      atmospheric ammonia in young trees.
AB  - The influence of carbon dioxide (CO2) and soil fertility on the physiological
      performance of plants has been extensively studied, but their combined effect is
      notoriously difficult to predict. Using Coffea arabica as a model tree species,
      we observed an additive effect on growth, by which aboveground productivity was
      highest under elevated CO2 and ammonium fertilization, while nitrate
      fertilization favored greater belowground biomass allocation regardless of CO2
      concentration. A pulse of labelled gases ((13)CO2 and (15)NH3) was administered
      to these trees as a means to determine the legacy effect of CO2 level and soil
      nitrogen form on foliar gas uptake and translocation. Surprisingly, trees with
      the largest aboveground biomass assimilated significantly less NH3 than the
      smaller trees. This was partly explained by declines in stomatal conductance in
      plants grown under elevated CO2. However, unlike the (13)CO2 pulse, assimilation
      and transport of the (15)NH3 pulse to shoots and roots varied as a function of
      interactions between stomatal conductance and direct plant response to the form
      of soil nitrogen, observed as differences in tissue nitrogen content and biomass
      allocation. Nitrogen form is therefore an intrinsic component of physiological
      responses to atmospheric change, including assimilation of gaseous nitrogen as
      influenced by plant growth history. 

PMID- 26294036
TI  - Metamorphic remodeling of the olfactory organ of the African clawed frog, Xenopus
      laevis.
AB  - The amphibian olfactory system undergoes massive remodeling during metamorphosis.
      The transition from aquatic olfaction in larvae to semiaquatic or airborne
      olfaction in adults requires anatomical, cellular, and molecular modifications.
      These changes are particularly pronounced in Pipidae, whose adults have
      secondarily adapted to an aquatic life style. In the fully aquatic larvae of
      Xenopus laevis, the main olfactory epithelium specialized for sensing water-borne
      odorous substances lines the principal olfactory cavity (PC), whereas a separate
      olfactory epithelium lies in the vomeronasal organ (VNO). During metamorphosis,
      the epithelium of the PC is rearranged into the adult "air nose," whereas a new
      olfactory epithelium, the adult "water nose," forms in the emerging middle cavity
      (MC). Here we performed a stage-by-stage investigation of the anatomical changes
      of the Xenopus olfactory organ during metamorphosis. We quantified cell death in
      all olfactory epithelia and found massive cell death in the PC and the VNO,
      suggesting that the majority of larval sensory neurons is replaced during
      metamorphosis in both sensory epithelia. The moderate cell death in the MC shows
      that during the formation of this epithelium some cells are sorted out. Our
      results show that during MC formation some supporting cells, but not sensory
      neurons, are relocated from the PC to the MC and that they are eventually
      eliminated during metamorphosis. Together our findings illustrate the structural
      and cellular changes of the Xenopus olfactory organ during metamorphosis.

PMID- 26294038
TI  - Electron Hopping through Redox Moieties Anchored to Well-Defined Nanostructures.

PMID- 26294037
TI  - Rapid and sensitive detection of calreticulin type 1 and 2 mutations by real-time
      quantitative PCR.
AB  - BACKGROUND: The majority of patients with JAK2 V617F-negative essential
      thrombocythemia or primary myelofibrosis harbor mutations involving the
      calreticulin (CALR) gene. These mutations are located in CALR exon 9 and lead to
      a frameshift with subsequent alteration of the CALR protein C-terminus. They have
      emerged as valuable molecular markers for the diagnosis of clonal
      myeloproliferative diseases. Although a variety of CALR mutations have been
      described, two mutations, denoted type 1 and type 2, account for around 85 % of
      cases. The type 1 mutation encompasses a 52 bp deletion and the type 2 mutation a
      5 bp TTGTC insertion. METHODS: This work describes the development and testing of
      quantitative real-time PCRs (qPCRs) for detecting these two mutations. RESULTS:
      The final type 1 CALR qPCR displayed a sensitivity of <0.1 % mutant alleles and
      the type 2 CALR qPCR had a sensitivity of <0.01 % mutant alleles. Additionally,
      two new CALR mutations are reported. CONCLUSION: These sensitive and specific
      qPCRs should be helpful in establishing the diagnosis and in monitoring minimal
      residual disease in patients during or after therapy.

PMID- 26294039
TI  - Editorial Comment on "Use of Hormone Testing for the Diagnosis and Evaluation of
      Male Hypogonadism and Monitoring of Testosterone Therapy: Application of Hormone
      Testing Guideline Recommendations in Clinical Practice".

PMID- 26294041
TI  - Ethnic Discrimination, Acculturative Stress, and Family Conflict as Predictors of
      Depressive Symptoms and Cigarette Smoking Among Latina/o Youth: The Mediating
      Role of Perceived Stress.
AB  - Latino youth can experience a range of cultural (i.e., ethnic discrimination and
      acculturative stress) and familial (i.e. family conflict) risk factors that can
      contribute to their perceived stress, thereby increasing their risk for
      depressive symptoms and cigarette smoking. To understand the mechanisms by which
      ethnic discrimination, acculturative stress and family conflict influence the
      risk for depressive symptoms and cigarette smoking of youth, the current study
      investigated the mediating role of perceived stress in these associations. The
      data came from a longitudinal study of acculturation and substance use with 1919
      Latino adolescents (52% female; 84% 14 year-olds; 87% U.S. born). Structural
      equation modeling indicated that discrimination and family conflict (Time 1)
      related with higher perceived stress (Time 2), which, in turn, related with more
      depressive symptoms and smoking (Time 3). The results suggest that perceived
      stress might be one mechanism by which ethnic discrimination and family conflict
      contribute to Latino youth symptoms of depression and cigarette smoking. The
      findings highlight the need for prevention and intervention strategies that help
      youth manage their general perceived stress and/or focus on stress reduction
      techniques.

PMID- 26294040
TI  - Persistent alterations of gene expression profiling of human peripheral blood
      mononuclear cells from smokers.
AB  - The number of validated biomarkers of tobacco smoke exposure is limited, and none
      exist for tobacco-related cancer. Additional biomarkers for smoke, effects on
      cellular systems in vivo are needed to improve early detection of lung cancer,
      and to assist the Food and Drug Administration in regulating exposures to tobacco
      products. We assessed the effects of smoking on the gene expression using human
      cell cultures and blood from a cross-sectional study. We profiled global
      transcriptional changes in cultured smokers' peripheral blood mononuclear cells
      (PBMCs) treated with cigarette smoke condensate (CSC) in vitro (n = 7) and from
      well-characterized smokers' blood (n = 36). ANOVA with adjustment for covariates
      and Pearson correlation were used for statistical analysis in this study. CSC in
      vitro altered the expression of 1 178 genes (177 genes with > 1.5-fold-change) at
      P < 0.05. In vivo, PBMCs of heavy and light smokers differed for 614 genes (29
      with > 1.5-fold-change) at P < 0.05 (309 remaining significant after adjustment
      for age, race, and gender). Forty-one genes were persistently altered both in
      vitro and in vivo, 22 having the same expression pattern reported for non-small
      cell lung cancer. Our data provides evidence that persistent alterations of gene
      expression in vitro and in vivo may relate to carcinogenic effects of cigarette
      smoke, and the identified genes may serve as potential biomarkers for cancer. The
      use of an in vitro model to corroborate results from human studies provides a
      novel way to understand human exposure and effect. (c) 2015 Wiley Periodicals,
      Inc.

PMID- 26294042
TI  - How Do My Friends Matter? Examining Latino Adolescents' Friendships, School
      Belonging, and Academic Achievement.
AB  - Are Latino adolescents' friendships an untapped resource for academic achievement
      or perhaps one of the reasons why these youth struggle academically? Using data
      from the National Longitudinal Study of Adolescent Health (N = 6782; 7th through
      12th graders; 52.9 % female), we examined whether the process of Latino students'
      school belonging mediated the relationships between the context of friendships
      (i.e., friendship network indicators) and their academic outcomes (i.e., a
      context-process-outcomes model), and tested whether the process-context link
      varied by friends' characteristics (i.e., GPA and problem behavior; social
      capital). Moreover, we tested whether all relationships varied across the four
      largest Latino subgroups in the U.S. (i.e., Mexican, Central/South American,
      Puerto Rican, and Cuban). Our findings indicate that being nominated as a friend
      by peers and perceiving to have friends exerted both direct effects on school
      belonging in all but one of the Latino ethnic samples (i.e., Puerto Rican
      samples) and indirect effects on academic achievement in the full Latino,
      Mexican, and Central/South American samples. As such, school belonging was more
      likely to explain the links between academic achievement with nominations by
      peers as a friend and perceived friends than with having close-knit friendship
      groups. However, having a close-knit group of average or low-achieving friends
      predicted more school belonging for Mexican youth, but less school belonging for
      Cubans. Our findings suggest that friendships may be particularly beneficial for
      the school belonging process of highly marginalized groups in the U.S. (i.e.,
      Mexican-origin). 

PMID- 26294044
TI  - Novel Rod Domain Duplication in Dystrophin Resulting in X-Linked Dilated
      Cardiomyopathy.
AB  - BACKGROUND: X-linked dilated cardiomyopathy is a rare, cardio-specific form of
      dystrophinopathy allelic to Duchenne and Becker muscular dystrophy that results
      in heart failure without skeletal muscle weakness. PATIENT DESCRIPTION: We
      describe a previously healthy 16-year-old boy who presented with palpitations
      progressing to heart failure who was ultimately found to have a novel duplication
      of exons 13-16 in the dystrophin gene resulting in diagnosis of X-linked dilated
      cardiomyopathy. RESULTS: The patient was diagnosed with X-linked dilated
      cardiomyopathy through clinical diagnosis and genetic testing. CONCLUSION: X
      linked dilated cardiomyopathy shares genotypic overlap with Duchenne and Becker
      muscular dystrophy, with its distinctive feature being a lack of progressive
      muscular weakness.

PMID- 26294043
TI  - Cas9-Guide RNA Directed Genome Editing in Soybean.
AB  - Recently discovered bacteria and archaea adaptive immune system consisting of
      clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR
      associated (Cas) endonuclease has been explored in targeted genome editing in
      different species. Streptococcus pyogenes Cas9-guide RNA (gRNA) was successfully
      applied to generate targeted mutagenesis, gene integration, and gene editing in
      soybean (Glycine max). Two genomic sites, DD20 and DD43 on chromosome 4, were
      mutagenized with frequencies of 59% and 76%, respectively. Sequencing randomly
      selected transgenic events confirmed that the genome modifications were specific
      to the Cas9-gRNA cleavage sites and consisted of small deletions or insertions.
      Targeted gene integrations through homology-directed recombination were detected
      by border-specific polymerase chain reaction analysis for both sites at callus
      stage, and one DD43 homology-directed recombination event was transmitted to T1
      generation. T1 progenies of the integration event segregated according to
      Mendelian laws and clean homozygous T1 plants with the donor gene precisely
      inserted at the DD43 target site were obtained. The Cas9-gRNA system was also
      successfully applied to make a directed P178S mutation of acetolactate synthase1
      gene through in planta gene editing. 

PMID- 26294045
TI  - Ongoing Cerebral Vasculitis During Treatment of Rocky Mountain Spotted Fever.
AB  - BACKGROUND: Rocky Mountain spotted fever is a tickborne infection that produces a
      systemic small-vessel vasculitis; its prognosis is excellent if appropriate
      treatment is initiated early. Because the advent of effective antirickettsial
      therapies predates the widespread use of brain magnetic resonance imaging, there
      are limited data on the effect of untreated Rocky Mountain spotted fever
      infection on neuroimaging studies. PATIENT DESCRIPTION: We describe a 7-year-old
      girl with delayed treatment of Rocky Mountain spotted fever who suffered severe
      neurological impairment. Serial brain magnetic resonance images revealed a
      progressive "starry sky appearance," which is proposed to result from the same
      small vessel vasculitis that causes the characteristic skin rash of this
      infection. CONCLUSION: Neurological injury can continue to occur despite specific
      antirickettsial therapy in Rocky Mountain spotted fever. This child's clinical
      features raise questions about the optimal management of this infection,
      particularly the utility of immune modulating therapies in cases of delayed
      treatment and neurological involvement.

PMID- 26294046
TI  - TUBA1A Mutation Associated With Eye Abnormalities in Addition to Brain
      Malformation.
AB  - OBJECTIVE: We describe the case of a boy with a TUBA1A mutation presenting with
      microphthalmia and congenital cataracts in addition to microcephaly and severe
      brain malformation. METHODS: A boy presented in early infancy with
      microphthalmia, congenital cataracts, and microcephaly. His neurological course
      included severe hypotonia and drug-resistant epilepsy. Magnetic resonance imaging
      of the brain revealed a complex malformation that included agenesis of the corpus
      callosum, severely hypoplastic cerebellar vermis, mildly hypoplastic and
      dysplastic cerebellar hemispheres, mildly hypoplastic brainstem, mild posterior
      simplified cerebral gyral pattern, dysplastic basal ganglia and thalami,
      hypoplastic optic nerves, and absent olfactory bulbs. RESULTS: TUBA1A genetic
      testing was conducted and revealed a previously unreported heterozygous 808G>T
      missense mutation. Parental genetic testing was negative, indicating that the
      child's mutation was de novo. CONCLUSION: The TUBA1A gene encodes tubulin alpha
      1A, a protein with an important role in microtubule function and stability. Human
      mutations can result in a wide spectrum of brain malformations including
      lissencephaly, microlissencephaly, cerebellar hypoplasia, agenesis of the corpus
      callosum, pachygyria and polymicrogyria. Although TUBA1A is expressed in both
      developing brain and retinal tissue, there are no reported cases of TUBA1A
      mutations in association with major developmental ophthalmologic abnormalities.

PMID- 26294047
TI  - Calorimetric determination of the magnetic phase diagram of underdoped ortho II
      YBa2Cu3O6.54 single crystals.
AB  - The recent discovery of a charge order in underdoped YBa2Cu3Oy raised the
      question of the interplay between superconductivity and this competing phase.
      Understanding the normal state of high-temperature superconductors is now an
      essential step towards the description of the pairing mechanism in those
      materials and determining the upper critical field is therefore of fundamental
      importance. We present here a calorimetric determination of the field-temperature
      phase diagram in underdoped YBa2Cu3Oy single crystals. We show that the specific
      heat saturates in high magnetic fields. This saturation is consistent with a
      normal state without any significant superconducting contribution and a total
      Sommerfeld coefficient gammaN~6.5+/-1.5 mJ mol(-1) K(-2) putting strong
      constraints on the theoretical models for the Fermi surface reconstruction. 

PMID- 26294048
TI  - Natural disturbance reduces disease risk in endangered rainforest frog
      populations.
AB  - Natural disturbances can drive disease dynamics in animal populations by altering
      the microclimates experienced by hosts and their pathogens. Many pathogens are
      highly sensitive to temperature and moisture, and therefore small changes in
      habitat structure can alter the microclimate in ways that increase or decrease
      infection prevalence and intensity in host populations. Here we show that a
      reduction of rainforest canopy cover caused by a severe tropical cyclone
      decreased the risk of endangered rainforest frogs (Litoria rheocola) becoming
      infected by a fungal pathogen (Batrachochytrium dendrobatidis). Reductions in
      canopy cover increased the temperatures and rates of evaporative water loss in
      frog microhabitats, which reduced B. dendrobatidis infection risk in frogs by an
      average of 11-28% in cyclone-damaged areas, relative to unaffected areas. Natural
      disturbances to the rainforest canopy can therefore provide an immediate benefit
      to frogs by altering the microclimate in ways that reduce infection risk. This
      could increase host survival and reduce the probability of epidemic disease
      outbreaks. For amphibian populations under immediate threat from this pathogen,
      targeted manipulation of canopy cover could increase the availability of warmer,
      drier microclimates and therefore tip the balance from host extinction to
      coexistence. 

PMID- 26294049
TI  - Effect of a high intake of cheese on cholesterol and metabolic syndrome: results
      of a randomized trial.
AB  - BACKGROUND: Cheese is generally rich in saturated fat, which is associated with
      increased risk for cardiovascular diseases. Nevertheless, recent reports suggest
      that cheese may be antiatherogenic. OBJECTIVE: The goal of this study was to
      assess whether intake of two types of Norwegian cheese, with widely varying fat
      and calcium content, might influence factors of the metabolic syndrome and serum
      cholesterol levels differently. DESIGN: A total of 153 participants were
      randomized to one of three groups: Gamalost((r)), a traditional fat- and salt
      free Norwegian cheese (50 g/day), Gouda-type cheese with 27% fat (80 g/day), and
      a control group with a limited cheese intake. Blood samples, anthropometric
      measurements, blood pressure, and questionnaires about lifestyle and diet were
      obtained at inclusion and end. RESULTS: At baseline, there were no differences
      between the groups in relevant baseline characteristics, mean age 43, 52.3%
      female. After 8 weeks' intervention, there were no changes in any of the
      metabolic syndrome factors between the intervention groups compared with the
      control group. There were no increases in total- or LDL cholesterol in the cheese
      groups compared with the control. Stratified analysis showed that those in the
      Gouda group with metabolic syndrome at baseline had significant reductions in
      total cholesterol at the end of the trial compared with control (-0.70 mmol/L,
      p=0.013), and a significantly higher reduction in mean triglycerides. In the
      Gamalost group, those who had high total cholesterol at baseline had a
      significant reduction in total cholesterol compared with control (-0.40 mmol/L,
      p=0.035). CONCLUSIONS: In conclusion, cholesterol levels did not increase after
      high intake of 27% fat Gouda-type cheese over 8 weeks' intervention, and
      stratified analysis showed that participants with metabolic syndrome had reduced
      cholesterol at the end of the trial.

PMID- 26294050
TI  - Stochastic binding of Staphylococcus aureus to hydrophobic surfaces.
AB  - The adhesion of pathogenic bacteria to surfaces is of immense importance for
      health care applications. Via a combined experimental and computational approach,
      we studied the initiation of contact in the adhesion process of the pathogenic
      bacterium Staphylococcus aureus. AFM force spectroscopy with single cell
      bacterial probes paired with Monte Carlo simulations enabled an unprecedented
      molecular investigation of the contact formation. Our results reveal that
      bacteria attach to a surface over distances far beyond the range of classical
      surface forces via stochastic binding of thermally fluctuating cell wall
      proteins. Thereby, the bacteria are pulled into close contact with the surface as
      consecutive proteins of different stiffnesses attach. This mechanism greatly
      enhances the attachment capability of S. aureus. It, however, can be manipulated
      by enzymatically/chemically modifying the cell wall proteins to block their
      consecutive binding. Our study furthermore reveals that fluctuations in protein
      density and structure are much more relevant than the exact form of the binding
      potential. 

PMID- 26294051
TI  - Seizures associated with intentional severe nutmeg intoxication.

PMID- 26294052
TI  - Primary Care Providers' Knowledge and Practices of Diabetes Management During
      Ramadan.
AB  - There are an estimated 3.5 million Muslims in North America. During the holy
      month of Ramadan, healthy adult Muslims are to fast from predawn to after sunset.
      While there are exemptions for older and sick adults, many adults with diabetes
      fast during Ramadan. However, there are risks associated with fasting and
      specific management considerations for patients with diabetes. We evaluated
      provider practices and knowledge regarding the management of patients with
      diabetes who fast during Ramadan. A 15-question quality improvement survey based
      on a literature review and the American Diabetes Association guidelines was
      developed and offered to providers at the outpatient primary care and geriatric
      clinics at an inner-city hospital in New York City. Forty-five providers
      completed the survey. Most respondents did not ask their Muslim patients with
      diabetes if they were fasting during the previous Ramadan. Knowledge of fasting
      practices during Ramadan was variable, and most felt uncomfortable managing
      patients with diabetes during Ramadan. There is room for improvement in educating
      providers about specific cultural and medical issues regarding fasting for
      patients with diabetes during Ramadan. 

PMID- 26294053
TI  - Radiographic identification of the primary structures of the ankle syndesmosis.
AB  - PURPOSE: The purpose of this study was to quantitatively describe the locations
      of the syndesmotic ligaments and the tibiofibular articulating cartilage surfaces
      on standard radiographic views using reproducible radiographic landmarks and
      reference axes. METHODS: Twelve non-paired ankles were dissected to identify the
      anterior-inferior tibiofibular ligament (AITFL), posterior-inferior tibiofibular
      ligament (PITFL), interosseous tibiofibular ligament (ITFL), and the cartilage
      surfaces of the syndesmosis. Structures were marked with 2-mm radiopaque spheres
      prior to obtaining lateral and mortise radiographs. Measurements were performed
      by two independent raters to assess intra- and interobserver reliability via
      intraclass correlation coefficients (ICCs). RESULTS: Measurements demonstrated
      excellent agreement between observers and across trials (all ICCs >= 0.960). On
      the lateral view, the AITFL tibial origin was 9.6 +/- 1.5 mm superior and
      posterior to the anterior tibial plafond. Its fibular insertion was 4.4 +/- 1.7
      mm superior and posterior to the anterior fibular tubercle. The centre of the
      tibial cartilage facet of the tibiofibular contact zone was 8.4 +/- 2.1 mm
      posterior and superior to the anterior plafond. The proximal and distal aspects
      of the ITFL tibial attachment were 45.9 +/- 7.9 and 12.4 +/- 3.4 mm proximal to
      the central plafond, respectively. The superficial and deep PITFL coursed
      anterior and distally from the posterior tibia to fibula. On the mortise view,
      the AITFL tibial attachment centre was 5.6 +/- 2.4 mm lateral and superior to the
      lateral extent of the plafond (4.3 mm lateral, 3.3 mm superior), and its fibular
      insertion was 21.2 +/- 2.1 mm superior and medial to the inferior tip of the
      lateral malleolus. CONCLUSIONS: Quantitative radiographic guidelines describing
      the locations of the primary syndesmotic structures demonstrated excellent
      reliability and reproducibility. Defined guidelines provide additional clinically
      relevant information regarding the radiographic anatomy of the syndesmosis and
      may assist with preoperative planning, augment intraoperative navigation, and
      provide additional means for objective postoperative assessment.

PMID- 26294054
TI  - The role of high tibial osteotomy in the treatment of knee laxity: a
      comprehensive review.
AB  - PURPOSE: The purpose of this study is to review the indications for and outcomes
      of high tibial osteotomy in the treatment of patients with chronic knee laxity.
      METHODS: A comprehensive literature review was performed to identify surgical
      indications and results of high tibial osteotomy for the treatment of chronic
      knee laxity. RESULTS: Four distinct situations were identified in which a high
      tibial osteotomy may be advantageous: (1) anterior laxity with varus
      osteoarthritis, (2) chronic anterior laxity in the setting of varus with lateral
      ligamentous laxity, (3) chronic anterior laxity in the setting of a high tibial
      slope, and (4) chronic posterior laxity or posterolateral corner injury. A total
      of 24 studies were included in this report, including reports of the treatment of
      410 knees as well as several review articles. The most frequently reported
      indication for that addition of HTO was anterior laxity in the setting of varus
      OA, which was noted to have good results, minimizing anterior knee laxity and
      allowing return to sports, while reducing the progression of osteoarthritis. More
      advanced cases in which lateral structures have also become stretched and
      incompetent are an excellent indication for HTO, with the need for subsequent
      lateral procedures dependent on the degree of varus laxity and especially
      hyperextension that is present. Excessive tibial slope has been identified as a
      cause of ACL reconstruction failure, and some authors have recommended addressing
      very high slope in revision cases. In knees with chronic posterior or
      posterolateral instability, correction of alignment first is generally
      recommended, with subsequent ligamentous procedures performed when instability
      persists. CONCLUSIONS: Knees with chronic instability pose a difficult treatment
      challenge. In all cases, the contribution of coronal plane alignment to varus
      valgus knee stability must be carefully considered and addressed prior to
      ligament surgery. Sagittal plane alignment is also key and must not be
      overlooked. Such considerations drive the indication for osteotomy as well as the
      type of osteotomy that is chosen. Level of evidence IV.

PMID- 26294055
TI  - Eccentric and isometric shoulder rotator cuff strength testing using a hand-held
      dynamometer: reference values for overhead athletes.
AB  - PURPOSE: In order to provide science-based guidelines for injury prevention or
      return to play, regular measurement of isometric and eccentric internal (IR) and
      external (ER) rotator strength is warranted in overhead athletes. However, up to
      date, no normative database exists regarding these values, when measured with a
      hand-held dynamometer. Therefore, the purpose of the study was to provide a
      normative database on isometric and eccentric rotator cuff (RC) strength values
      in a sample of overhead athletes, and to discuss gender, age and sports
      differences. METHODS: A HHD was used to measure RC strength in 201 overhead
      athletes between 18 and 50 years old from three different sports disciplines:
      tennis, volleyball and handball. Isometric as well as eccentric strength was
      measured in different shoulder positions. Outcome variables of interest were
      isometric ER and IR strength, eccentric ER strength, and intermuscular strength
      ratios ER/IR. RESULTS: Our results show significant side, gender and sports
      discipline differences in the isometric and eccentric RC strength. However, when
      normalized to body weight, gender differences often are absent. In general,
      strength differences are in favour of the dominant side, the male athletes and
      handball. Intermuscular ER/IR ratios showed gender, sports, and side differences.
      CONCLUSION: This normative database is necessary to help the clinician in the
      evaluation of RC strength in healthy and injured overhead athletes. In view of
      the preventive screening and return-to-play decisions in overhead athletes,
      normalization to body weight and calculating intermuscular ratios are key points
      in this evaluation. LEVEL OF EVIDENCE: Diagnostic study, Level III.

PMID- 26294056
TI  - Bone mineral decreases in the calcanei in men after arthroscopic shoulder
      surgery: a prospective study over 5 years.
AB  - PURPOSE: It is well known that injuries and surgical procedures in the lower
      extremities affect bone mineral both in the injured limb and in the contralateral
      limb. The possible effect on bone mineral after upper extremity surgery is not
      well studied, and the aim of this study was to study the effect on bone mineral
      in the calcanei after arthroscopic shoulder surgery. METHODS: Twenty-two men
      scheduled for arthroscopic shoulder surgery underwent bone mineral area (BMA)
      mass measurements in both calcanei using the Calscan DXL device prior to surgery
      and after 6, 18, 36 and 60 months. On every occasion, the Tegner activity score
      and EuroQoL 5-dimensions (EQ-5D) were assessed. RESULTS: During 5 years, there
      was a significant decrease in the BMA in both calcanei (p = 0.003). The Tegner
      activity score decreased from preinjury to the operation and did not increase
      significantly after the operation. The EQ-5D increased significantly after the
      operation. CONCLUSION: The bone mineral in the calcanei in men during the 5-year
      study period decreased more than the expected age-dependent decline after
      arthroscopic shoulder surgery. There was an increase in health-related quality of
      life as measured with the EQ-5D after arthroscopic Bankart reconstruction. LEVEL
      OF EVIDENCE: Case-control study, Level III.

PMID- 26294057
TI  - Effects of femoral bone tunnel characteristics on graft-bending angle in double
      bundle anterior cruciate ligament reconstruction: a comparison of the outside-in
      and transportal techniques.
AB  - PURPOSE: Bone tunnel creation techniques influence the 3-dimensional (3D)
      position of bone tunnels and graft-bending angle in anterior cruciate ligament
      (ACL) reconstruction. This study assessed graft-bending angle and 3D
      characteristics of femoral bone tunnels and compared them between outside-in (OI)
      and transportal (TP) techniques. METHODS: Participants comprised 64 patients who
      underwent anatomic double-bundle ACL reconstruction, allocated to OI and TP
      groups (n = 32 each). The graft orientation plane exhibiting the largest graft
      bending angle at the femoral tunnel aperture with the knee in extension was
      reconstructed from CT data using 3D imaging software. In this plane, graft
      bending angle was compared between the OI and TP techniques. RESULTS: Although
      positionings of the intra-articular apertures of the femoral and tibial bone
      tunnels were similar, several spatial parameters of bone tunnels differed between
      techniques. Graft-bending angles of both anteromedial and posterolateral bundles
      were significantly more acute with the OI technique than with the TP technique.
      On coronal-plane CT, angle of the bone tunnel axis relative to the distal
      condylar axis correlated negatively with graft-bending angle, while in the axial
      plane, angle of the bone tunnel axis relative to the posterior condylar axis
      correlated positively with graft-bending angle. Lysholm score, pivot shift test,
      and anteroposterior laxity at >2.5-year follow-up demonstrated no significant
      differences between techniques. DISCUSSION: Different bone tunnel directions in
      OI and TP techniques substantially affected graft-bending angle , despite similar
      positionings of the intra-articular apertures. Graft-bending angle with the OI
      technique was acute, but risk of posterior blowout of the lateral femoral condyle
      was decreased. Surgeons should create the femoral tunnel while considering an
      obtuse graft-bending angle without increasing the risk of posterior blowout.
      LEVEL OF EVIDENCE: III.

PMID- 26294058
TI  - Role of Msi1 and MAML1 in Regulation of Notch Signaling Pathway in Patients with
      Esophageal Squamous Cell Carcinoma.
AB  - PURPOSE: Developmental pathways such as Wnt and Notch are involved in different
      cellular functions from the cell cycle regulation to self-renewal. Therefore,
      aberrations in these pathways may cause tumorigenesis. Msi1 has a critical
      regulatory role for the Wnt and Notch pathways. In the present study, we have
      assessed the probable correlation between the Msi1 and MAML1 in esophageal
      squamous cell carcinoma (ESCC) progression and metastasis. METHODS: Levels of
      Msi1 and MAML1 mRNA expression in 51 ESCC patients were compared to the normal
      tissues using real-time polymerase chain reaction (PCR). RESULTS: Nine out of 51
      (17.6 %) cases had Msi1/MAML1 overexpression, and there was a significant
      correlation between such overexpressed cases and tumor location (p = 0.013).
      CONCLUSIONS: We showed that there is not any direct correlation and feedback
      between the Msi1 and MAML1 in ESCC patients.

PMID- 26294060
TI  - Selective Protection of Secondary Amines as the N-Phenyltriazenes. Application to
      Aminoglycoside Antibiotics.
AB  - Selective protection of secondary amines as triazenes in the presence of multiple
      primary amines is demonstrated, with subsequent protection of the primary amines
      as either azides or carbamates in the same pot. Aminoglycoside antibiotic
      examples reveal broad functional group compatibility. The triazene group is
      removed with trifluoroacetic acid and, because of the low barrier to rotation,
      affords sharp (1)H NMR spectra at room temperature. 

PMID- 26294059
TI  - Preoperative Intrasac Thrombus Load Predicts Worse Outcome after Elective
      Endovascular Repair of Abdominal Aortic Aneurysms.
AB  - PURPOSE: To evaluate the impact of two-dimensional and three-dimensional
      preoperative morphologic features analyzed on computed tomography (CT)
      angiography on midterm outcome in patients with abdominal aortic aneurysms (AAAs)
      treated with endovascular aneurysm repair (EVAR). MATERIALS AND METHODS: A
      retrospective analysis was conducted using a prospectively collected database.
      Morphologic features considered as potentially influencing outcomes were maximum
      aortic diameter, thrombus area, overall aneurysm volume, and intrasac thrombus
      volume. Outcome measures were all perioperative and midterm AAA-related
      reinterventions and all-cause mortality. RESULTS: Investigators reviewed 191
      preoperative CT angiography scans. Mean maximum aortic diameter was 58 mm;
      thrombus area, 49.6%; aortic volume, 159.36 cm(3); and thrombus volume, 58.6%.
      Technical success was achieved in all cases. No reintervention was required in
      the perioperative period, and there was no perioperative mortality. At a mean
      follow-up of 32 months +/- 16.8 (range, 3-66 mo), mortality rate was 9.4%, AAA
      related death was 0, and reintervention rate was 8.9%. Causes of reintervention
      included type I endoleak (n = 3 [1.6%]), type II endoleak (n = 7 [3.7%]), type
      III endoleak (n = 1 [0.5%]), endograft limb thrombosis (n = 4 [2.1%]), and access
      vessel thrombosis (n = 2; 1%). Greater thrombus area (> 60%) and thrombus volume
      (> 59%) were predictors for reintervention (P = .005 and P = .0034). Greater
      maximum aortic diameter (> 59 mm) and aortic volume (> 159 cm(3)) were related to
      higher reintervention rate without statistical significance (P = .62 and P =
      .12). Aortic volume was a predictor of any adverse event, reintervention, and all
      cause mortality after EVAR (P = .03). CONCLUSIONS: Thrombus area and volume are
      related to higher rates of reintervention. Maximum aortic diameter was related to
      a higher reintervention rate, but this was not significant.

PMID- 26294061
TI  - Inter- and Intra-individual Variability in Response to Transcranial Direct
      Current Stimulation (tDCS) at Varying Current Intensities.
AB  - BACKGROUND: Translation of transcranial direct current stimulation (tDCS) from
      research to clinical practice is hindered by a lack of consensus on optimal
      stimulation parameters, significant inter-individual variability in response, and
      in sufficient intra-individual reliability data. OBJECTIVES: Inter-individual
      differences in response to anodal tDCS at a range of current intensities were
      explored. Intra-individual reliability in response to anodal tDCS across two
      identical sessions was also investigated. METHODS: Twenty-nine subjects
      participated in a crossover study. Anodal-tDCS using four different current
      intensities (0.2, 0.5, 1 and 2 mA), with an anode size of 16 cm2, was tested. The
      0.5 mA condition was repeated to assess intra-individual variability. TMS was
      used to elicit 40 motor-evoked potentials (MEPs) before 10 min of tDCS, and 20
      MEPs at four time-points over 30 min following tDCS. RESULTS: ANOVA revealed no
      main effect of TIME for all conditions except the first 0.5 mA condition, and no
      differences in response between the four current intensities. Cluster analysis
      identified two clusters for the 0.2 and 2 mA conditions only. Frequency
      distributions based on individual subject responses (excitatory, inhibitory or no
      response) to each condition indicate possible differential responses between
      individuals to different current intensities. Test-retest reliability was
      negligible (ICC(2,1) = -0.50). CONCLUSIONS: Significant inter-individual
      variability in response to tDCS across a range of current intensities was found.
      2 mA and 0.2 mA tDCS were most effective at inducing a distinct response.
      Significant intra-individual variability in response to tDCS was also found. This
      has implications for interpreting results of single-session tDCS experiments.

PMID- 26294062
TI  - 'I-wave' Recruitment Determines Response to tDCS in the Upper Limb, but Only So
      Far.
AB  - BACKGROUND: Anodal transcranial direct current stimulation (a-tDCS) can
      facilitate primary motor cortex (M1), but the modulation of motor evoked
      potentials (MEPs) by a-tDCS varies between participants, and may depend on the
      balance between early versus late I-wave recruitment, as assessed by the
      difference in MEP latency between latero-medial and anterior-posterior cortical
      currents induced by transcranial magnetic stimulation (TMS). OBJECTIVE: To date,
      the dependence of tDCS after-effects on I-wave recruitment has only been
      investigated in intrinsic hand muscles. In order to better understand the effects
      of tDCS across the upper limb, the present study examined I-wave recruitment and
      MEP modulation by a-tDCS or dual-hemisphere tDCS in muscles of the forearm
      (Extensor Carpi Radialis; ECR) and proximal upper limb (Biceps Brachii; BB).
      METHODS: We conducted a randomized double-blind study with 18 healthy adults.
      Each received anodal, dual-hemisphere, or sham tDCS over M1 in separate sessions
      (tDCS, 1 mA for 15 min). RESULTS: Linear regression analyzes showed a-tDCS
      modulated MEP size dependent on the latency difference in the ECR (P = 0.01) but
      not BB (P = 0.28). Individuals with small MEP latency differences showed the
      expected facilitation of ECR MEPs after a-tDCS, whereas those with large MEP
      latency differences had suppressed ECR MEPs after a-tDCS. This relationship was
      not present after dual-hemisphere or sham tDCS in either muscle (all P > 0.32).
      CONCLUSIONS: I-wave recruitment can predict the after-effects of a-tDCS in the
      distal but not proximal upper limb. These findings provide further insight into
      the variability of tDCS after-effects, and the relationship between I-wave
      recruitment and putative mechanisms of tDCS.

PMID- 26294063
TI  - Altered PCA3 and TMPRSS2-ERG expression in histologically benign regions of
      cancerous prostates: a systematic, quantitative mRNA analysis in five prostates.
AB  - BACKGROUND: PCA3 and TMPRSS2-ERG are commonly overexpressed biomarkers in
      prostate cancer, but reports have emerged demonstrating altered expression also
      in areas outside the tumour foci in cancerous prostates. Our aim was to measure
      PCA3 and TMPRSS2-ERG expression systematically in all regions of prostate cross
      sections, matching the data to corresponding tissue morphology. METHODS: TMPRSS2
      ERG and PCA3 mRNA levels were measured with quantitative reverse-transcription
      PCR assays in 270 samples from cross-sections of five radical prostatectomy
      specimens. ERG expression was examined by immunohistochemistry. RESULTS: TMPRSS2
      ERG mRNAs were detected in three patients and in 15 tissue samples in total.
      These included two carcinoma samples and 13 histologically benign samples, eight
      of which were located next to malignant tumours or PIN (prostatic intraepithelial
      neoplasia) lesions and five of which did not reside in the vicinity of any
      evident carcinoma foci. ERG protein expression was limited to areas of TMPRSS2
      ERG mRNA expression, but did not identify all of them. PCA3 expression was
      detected in all five cross-sections, with statistically significant, three-fold
      higher expression in carcinoma regions. CONCLUSIONS: TMPRSS2-ERG expression was
      detected in carcinoma foci, regions next to them, and in samples not adjacent to
      carcinoma foci. Claimed as a cancer-associated phenomenon, this fusion gene
      measurement could, if validated with a larger cohort, be utilized as an addition
      to histological analysis to predict current or future cancer risk in men with
      negative biopsies. Molecular changes outside the carcinoma foci are also
      indicated for PCA3, as its expression was only moderately increased in the
      carcinoma regions.

PMID- 26294064
TI  - A questionnaire to measure women's experiences with pregnancy, birth and
      postnatal care: instrument development and assessment following a national survey
      in Norway.
AB  - BACKGROUND: The Norwegian authorities monitor the quality of public health-care
      services, including from the patients' perspective. The aim of this paper is to
      describe the development and psychometric properties of a pregnancy- and
      maternity-care patients' experiences questionnaire (PreMaPEQ). METHODS: The
      PreMaPEQ and data collection procedures were developed based on a literature
      review, reference group activities, user interviews, cognitive interviews and a
      pilot test. The PreMaPEQ was then used in a national survey that included a
      retest distribution. The participants were identified from the hospital records
      where the birth took place. The invitation to take part was sent by mail and the
      questionnaire was distributed in electronic (i.e. via the Internet) and
      (subsequently) paper forms. The completed questionnaires were assessed using
      descriptive statistics, explorative factor analyses, psychometric measures and
      confirmatory factor analysis (CFA). RESULTS: The PreMaPEQ response rate for the
      national sample was 56.6% (N = 4904), and retest data were provided by 123 women.
      Statistics and theoretical considerations were used to construct 16 scales,
      covering the following 4 phases of the care: pregnancy control (4 scales), the
      delivery (3 scales), the postnatal hospital stay (5 scales) and the services in
      the public health clinic (4 scales). All scales had a Cronbach's alpha of >0.7,
      and all but three scales had an intraclass correlation coefficient for test
      retest stability of >0.700. CFA revealed a satisfactory fit between the
      questionnaire data and the model, with a four-factor solution of the care
      experiences with pregnancy, birth and postnatal care. CFA provided support for
      the suggested structures, and demonstrated that the first-order factors are
      indicators of a second-order factor. CONCLUSION: The PreMaPEQ appears to be an
      acceptable, valid and reliable tool for collecting women's experiences of the
      whole course of maternity care in health systems that have features in common
      with the Norwegian health system.

PMID- 26294065
TI  - Limonene inhibits streptococcal biofilm formation by targeting surface-associated
      virulence factors.
AB  - The present study explores the efficacy of limonene, a cyclic terpene found in
      the rind of citrus fruits, for antibiofilm potential against species of the genus
      Streptococcus, which have been deeply studied worldwide owing to their multiple
      pathogenic efficacy. Limonene showed a concentration-dependent reduction in the
      biofilm formation of Streptococcus pyogenes (SF370), with minimal biofilm
      inhibitory concentration (MBIC) of 400 MUg ml - 1. Limonene was found to possess
      about 75-95 % antibiofilm activity against all the pathogens tested, viz.
      Streptococcus pyogenes (SF370 and 5 clinical isolates), Streptococcus mutans
      (UA159) and Streptococcus mitis (ATCC 6249) at 400 MUg ml - 1 concentration.
      Microscopic analysis of biofilm architecture revealed a quantitative breach in
      biofilm formation. Results of a surface-coating assay suggested that the possible
      mode of action of limonene could be by inhibiting bacterial adhesion to surfaces,
      thereby preventing the biofilm formation cascade. Susceptibility of limonene
      treated Streptococcus pyogenes to healthy human blood goes in unison with gene
      expression studies in which the mga gene was found to be downregulated. Anti
      cariogenic efficacy of limonene against Streptococcus mutans was confirmed, with
      inhibition of acid production and downregulation of the vicR gene. Downregulation
      of the covR, mga and vicR genes, which play a critical role in regulating surface
      associated proteins in Streptococcus pyogenes and Streptococcus mutans,
      respectively, is yet further evidence to show that limonene targets surface
      associated proteins. The results of physiological assays and gene expression
      studies clearly show that the surface-associated antagonistic mechanism of
      limonene also reduces surface-mediated virulence factors. 

PMID- 26294066
TI  - Development of the scale of hygiene behaviors for nursing students.
AB  - BACKGROUND: There is a need to have an appropriate instrument to measure the
      hygiene behaviors for nursing students. This study was carried out to develop a
      Hygiene Behavior Scale (HBS). METHODS: The population of the study is composed of
      the students of students of nursing department. A total of 416 participants were
      included in this study. The students in the sampling group were asked to write a
      composition containing their feelings and thoughts about hygiene. These
      compositions were analysed and 87 items about positive and negative behaviors
      were determined. These items were presented to expert opinion and after necessary
      editions, reliability and validity analyses were conducted. RESULTS: The
      resulting HBS consists of 25 items across the following three domains: Personal
      hygiene, handwashing technique and food-related hygiene . The final model in
      confirmatory factor analysis showed that this 25-item HBS indicated a good fit of
      the model. The value of the Cronbach's a for the total scale was 0.90.
      CONCLUSIONS: The HBS is determined to be quite highly valid and reliable,
      sufficient measuring instrument to determine hygiene behaviors of nursing
      students.

PMID- 26294067
TI  - IgD multiple myeloma: Clinical, biological features and prognostic value of the
      serum free light chain assay.
AB  - IgD multiple myeloma (MM) is a rare subtype of myeloma, it affects less than 2%
      of patients with MM. To evaluate the clinical and prognostic attributes of serum
      free light chains (sFLCs) analysis, we examined 17 cases of IgD MM. From 1998 to
      2012, we obtained 1250 monoclonal gammapathies including 590 multiple myeloma and
      17 patients had IgD MM. With preponderance of men patients with a mean age at
      diagnosis of: 59+/-12years. Patients with IgD MM have a short survival (Median
      survival=9months). The presenting features included: bone pain (75%),
      lymphadenopathy (16%), hepatomegaly (25%), splenomegaly (8%), associated AL
      amyloidosis (6%), renal impairment function (82%), infections (47%),
      hypercalcemia (37%) and anemia (93%). Serum electrophoresis showed a subtle M
      spike (Mean=13.22+/-10g/L) in all patients associated to a hypogammaglobulinemia.
      There was an over-representation of Lambda light chain (65%); high serum beta2
      microglobulin in 91% and Bence Jones proteinuria was identified in 71%. The
      median rate of sFLCs kappa was 19.05mg/L and 296.75mg/L for sFLCs lambda. sFLCR
      was abnormal in 93% of patients and it showed concordance between baseline sFLCR
      and the survival (P=0.034). The contribution of FLC assay is crucial for the
      prognosis of patients with IgD MM. 

PMID- 26294068
TI  - Chemokine C-C motif ligand 18 expression correlates with tumor malignancy in
      breast cancer.
AB  - PURPOSE OF THE STUDY: To investigate whether CCL18 is involved in breast cancer,
      and the relationship between CCL18 and MVD (MVD was recognized by CD34) which is
      a well-accepted angiogenic maker of multiple cancers including breast cancer.
      PATIENTS AND METHODS: Immunohistochemistry staining for CCL18 and CD34 was
      performed on 179 cases, including 29 normal cases as control, 47 cases with
      benign breast diseases, and 103 cases with breast cancer. RESULTS: We found that
      CCL18 was significantly up-regulated in breast cancer samples as compared with
      benign tumors or normal breast tissues. Moreover, the expression level of CCL18
      increased with the size of tumors, the number of lymph node metastasis, and
      advancing tumor stage, suggesting that CCL18 expression correlates with tumor
      malignancy scales. At the same time, we found that MVD was also significantly
      over-expressed in cancer tissues as compared with normal control group and benign
      tumor group, but it was not significantly differentially expressed among tumors
      with different malignancy scale like CCL18, while the expression of MVD in CCL18
      positive breast cancer cases was higher than in the CCL18 negative breast cancer
      cases (P=0.016, P<0.05). CONCLUSION: CCL18 is involved in the development of
      breast cancer. CCL18 is a better biomarker than MVD in determining whether the
      tumor is malignant and the severity of malignancy of breast cancer.

PMID- 26294069
TI  - Prediction of enzyme inhibition and mode of inhibitory action based on
      calculation of distances between hydrogen bond donor/acceptor groups of the
      molecule and docking analysis: An application on the discovery of novel effective
      PTP1B inhibitors.
AB  - PTP1B is a protein tyrosine phosphatase involved in insulin receptor
      desensitization. PTP1B inhibition prolongs the activated state of the receptor,
      practically enhancing the effect of insulin. Thus PTP1B has become a drug target
      for the treatment of type II diabetes. PTP1b is an enzyme with multiple binding
      sites for competitive and allosteric inhibitors. Prediction of inhibitory action
      using docking analysis has limited success in case of enzymes with multiple
      binding sites, since the selection of the right crystal structure depends on the
      kind of inhibitor. In the present study, a two-step strategy for the prediction
      of PTP1b inhibitory action was applied to 12 compounds. Based on the study of
      known inhibitors, we isolated the structural characteristics required for binding
      to each binding site. As a first step, 3D-structures of the molecules were
      produced and their structural parameters were measured and used for prediction of
      the binding site of the compound. These results were used for the selection of
      the appropriate crystal structure for docking analysis of each compound, and the
      final prediction was based on the estimated binding energies. This strategy
      effectively predicted the activity of all compounds. A linear correlation was
      found between estimated binding energy and inhibition measured in vitro (r = 
      0.894). 

PMID- 26294071
TI  - Plasmonic nanograting enhanced quantum dots excitation for cellular imaging on
      chip.
AB  - We present the design and integration of a two-dimensional (2D) plasmonic
      nanogratings structure on the electrode of colloidal quantum dot-based light
      emitting diodes (QDLEDs) as a compact light source towards arrayed on-chip
      imaging of tumor cells. Colloidal quantum dots (QDs) were used as the emission
      layer due to their unique capabilities, including multicolor emission, narrow
      bandwidth, tunable emission wavelengths, and compatibility with silicon
      fabrication. The nanograting, based on a metal-dielectric-metal plasmonic
      waveguide, aims to enhance the light intensity through the resonant reflection of
      surface plasmon (SP) waves. The key parameters of plasmonic nanogratings,
      including periodicity, slit width, and thicknesses of the metal and dielectric
      layers, were designed to tailor the frequency bandgap such that it matches the
      wavelength of operation. We fabricated QDLEDs with the integrated nanogratings
      and demonstrated an increase in electroluminescence intensity, measured along the
      direction perpendicular to the metal electrode. We found an increase of 34.72% in
      QDLED electroluminescence intensity from the area of the pattern and an increase
      of 32.63% from the photoluminescence of QDs deposited on a metal surface. We
      performed ex vivo transmission-mode microscopy to evaluate the nucleus-cytoplasm
      ratios of MDA-MB 231 cultured breast cancer cells using QDLEDs as the light
      source. We showed wavelength dependent imaging of different cell components and
      imaging of cells at higher magnification using enhanced emission from QDLEDs with
      integrated plasmonic nanogratings. 

PMID- 26294070
TI  - Low-dose isoflavone aglycone alleviates psychological symptoms of menopause in
      Japanese women: a randomized, double-blind, placebo-controlled study.
AB  - PURPOSE: Many studies have demonstrated the effectiveness of isoflavones on
      menopausal symptoms; however, these mostly used high dosages. Because high-dose
      isoflavone may result in endometrial hyperplasia, we investigated whether low
      dose isoflavone aglycone alleviates menopausal symptoms similarly to high
      dosages. METHODS: We conducted a randomized, double-blind, placebo-controlled
      study in 90 healthy women aged 40-60 years who had at least one menopausal
      symptom on the Menopausal Symptom Scale (MSS). The participants were randomized
      to receive active tablets containing ultralow-dose (12.5 mg/day; n = 30) or low
      dose (25 mg/day; n = 30) isoflavone aglycone, or placebo (n = 30) tablets, for 8
      weeks. Their menopausal symptoms were evaluated using MSS, Hospital Anxiety and
      Depression Scale (HADS), and Athens Insomnia Scale (AIS) before, and 4 and 8
      weeks after treatment. RESULTS: Eighty-seven women (97 %) completed the 8-week
      treatment. In the low-dose group, significant improvement was observed from
      baseline, in the following parameters: (1) HADS-depression subscale score, (2)
      AIS score, (3) MSS-somatic symptom score after 4 and 8 weeks of treatment, and
      (4) MSS-vasomotor symptom score after 8 weeks of treatment. The changes in scores
      on HADS-depression subscale and AIS from baseline to 8 weeks were significantly
      higher in the low-dose group than in the placebo group. CONCLUSIONS: Low-dose (25
      mg/day) isoflavone aglycone significantly alleviated symptoms of depression and
      insomnia in Japanese middle-aged women. Clinical Trial Registration UMIN-CTR
      UMIN000011876.

PMID- 26294072
TI  - Factors to consider in the choice of intrathecal drug in the treatment of
      neuropathic pain.
AB  - Medication selection for neuropathic pain follows a path of evidence, with
      respect to appreciating the patient's entry into the pain care algorithm. As we
      decide how to approach neuropathic pain, the considerations for intrathecal
      therapy medication selection are bound by catheter location, region of pain, and
      patient selection, to name a few. Future research and the 2016 polyanalgesic
      consensus conference may further provide patient care through a mindful eye on
      the improvement of patient safety and a reduction of the societal needs of
      opioids. 

PMID- 26294073
TI  - Olodaterol + tiotropium bromide for the treatment of chronic obstructive
      pulmonary disease.
AB  - A solid scientific rationale and an increasing body of clinical evidence for
      combining a beta2-agonist with an antimuscarinic agent in COPD fully support the
      opinion that patients not controlled by a single bronchodilator should be given
      two bronchodilators with different mechanisms of action. Tiotropium is an
      established choice for the management of patients with stable COPD, and
      olodaterol is a new effective and safe once-daily long-acting beta2-agonist. The
      parallel bronchodilating modes of action of olodaterol and tiotropium make them
      an attractive combination in COPD. The large ongoing TOviTO Phase III trial
      program is documenting the efficacy and safety of olodaterol/tiotropium fixed
      dose combination delivered via the Respimat Soft Mist Inhaler as maintenance
      therapy in patients with moderate to very severe COPD. However, we must still
      know whether this fixed-dose combination will affect exacerbations and
      hospitalizations, and ultimately death, and also the precise estimates of its
      relative cardiovascular safety. 

PMID- 26294074
TI  - Serelaxin a novel treatment for acute heart failure.
AB  - Acute heart failure (AHF) represents a major healthcare burden with a high risk
      of in-hospital and post-discharge mortality, which remained almost unchanged in
      the last few decades, underscoring the need of new treatments. Relaxin is a
      naturally occurring human peptide initially identified as a reproductive hormone
      and has been shown to play a key role in the maternal hemodynamic and renal
      adjustments that accommodate pregnancy. Recently, the new molecule serelaxin, a
      recombinant form of the naturally occurring hormone relaxin has been studied in
      patients hospitalized for AHF. In addition to vasodilation, serelaxin has anti
      oxidative, anti-inflammatory and connective tissue regulating properties. In
      preclinical studies, it reduced both systemic and renal vascular resistance and,
      in the clinical trials Pre-RELAX-AHF and RELAX-AHF, it improved dyspnea and signs
      of congestion. In addition, serelaxin was associated with a reduction of 180-day
      mortality. The aim of this review is to summarize the pharmacological properties
      of serelaxin and the results of the preclinical and clinical studies. 

PMID- 26294075
TI  - Novel treatment options for juvenile idiopathic arthritis.
AB  - The purpose of this review is to summarize the newer and possible future
      treatments for the arthritis and systemic features in children with juvenile
      idiopathic arthritis (JIA), including evidence supporting their efficacy and
      safety. 

PMID- 26294076
TI  - Biosimilar regulation in the EU.
AB  - In the EU, the EMA has been working with biosimilars since 1998. This experience
      is crystallized in the extensive set of guidelines, which range from basic
      principles to details of clinical trials. While the guidance may appear
      complicated, it has enabled the development of biosimilars, of which 21 have
      managed to get marketing authorization. Currently marketed biosimilars in the EU
      have a good track record in safety and traceability. No biosimilars have been
      withdrawn from the market because of safety concerns. The most controversial
      issues with biosimilars are immunogenicity and extrapolation of therapeutic
      indications. The available data for these topics do not raise concerns among EU
      regulators. Interchangeability and substitution are regulated by individual EU
      member states. 

PMID- 26294079
TI  - How should we evaluate non-pharmacological treatments in child and adolescent
      psychiatry?

PMID- 26294077
TI  - [Pharmacological aspects of pain research in Germany].
AB  - In spite of several approved analgesics, the therapy of pain still constitutes a
      challenge due to the fact that the drugs do not exert sufficient efficacy or are
      associated with severe side effects. Therefore, the development of new and
      improved painkillers is still of great importance. A number of highly qualified
      scientists in Germany are investigating signal transduction pathways in pain,
      effectivity of new drugs and the so far incompletely investigated mechanisms of
      well-known analgesics in preclinical and clinical studies. The highlights of
      pharmacological pain research in Germany are summarized in this article. 

PMID- 26294078
TI  - Early childhood psychological factors and risk for bedwetting at school age in a
      UK cohort.
AB  - There is evidence for a link between psychological factors and bedwetting, but
      the direction of this association is unclear. Using data on 8769 children from
      the Avon Longitudinal Study of Parents and Children, we examined whether
      difficult temperament (Toddler Temperament Scale at 24 months; Emotionality
      Activity Sociability Questionnaire at 38 months) and psychological problems
      (Revised Rutter Parent Scale for Preschool Children at 42 months) are linked to
      bedwetting at school age. We examined the association between these risk factors
      and different patterns of bedwetting from 4 to 9 years using multinomial
      regression. Difficult temperament and psychological problems in early childhood
      were associated with increased odds of bedwetting at 4-9 years. The strongest
      associations were most often found for the pattern of bedwetting that was both
      frequent (at least twice a week) and persistent (up to age 9) e.g. the
      temperament traits of 'adaptability' and 'mood' were associated with a 33 %
      increase (95 % confidence interval = 1.14-1.55) and a 27 % increase (1.10-1.47)
      respectively in the odds of persistent and frequent bedwetting per one standard
      deviation increase in risk score. Early behaviour problems (e.g. conduct problems
      [1.43 (1.25, 1.63)] and hyperactivity [1.29 (1.11, 1.50), p < 0.001]) were also
      associated with frequent and persistent bedwetting, but there was less evidence
      that early emotional difficulties were risk factors for bedwetting. Adjustment
      for confounders did not alter these conclusions. The presence of difficult
      temperament and behaviour problems in early childhood might help to identify
      children who will continue to experience bedwetting at school age. 

PMID- 26294080
TI  - MicroRNA-107 contributes to post-stroke angiogenesis by targeting Dicer-1.
AB  - Previous studies have suggested that microRNA-107 (miR-107) regulates cell
      migration in tumor and promotes Hypoxia Inducible Factor 1alpha (HIF1alpha)
      regulated angiogenesis under hypoxia. We found that miR-107 was strongly
      expressed in ischemic boundary zone (IBZ) after permanent middle cerebral artery
      occlusion (pMCAO) in rats and inhibition of miR-107 could reduce capillary
      density in the IBZ after stroke. Such finding led us to hypothesize that miR-107
      might regulate post-stroke angiogenesis and therefore serve as a therapeutic
      target. We also found that antagomir-107, a synthetic miR-107 inhibitor,
      decreased the number of capillaries in IBZ and increased overall infarct volume
      after pMCAO in rats. We demonstrated that miR-107 could directly down-regulate
      Dicer-1, a gene that encodes an enzyme essential for processing microRNA (miRNA)
      precursors. This resulted in translational desupression of VEGF (vascular
      endothelial growth factor) mRNA, thereby increasing expression of endothelial
      cell-derived VEGF (VEGF165/VEGF164), leading to angiogenesis after stroke. This
      process might be a protective mechanism for ischemia-induced cerebral injury and
      miR-107 might be used as a novel tool in stroke treatment. 

PMID- 26294081
TI  - Determining criminal responsibility: How relevant are insight and personal
      attitudes to mock jurors?
AB  - High levels of insight are interpreted as indications of a treatment compliance
      and good outcome by clinical professionals. However, it is unclear whether a
      defendant's insight plays a role in the decision-making of jurors when
      determining criminal responsibility. It may be the case that personal biases and
      attitudes toward the mentally ill and the insanity defense are more relevant in
      such decisions. This study examines the influence of two core dimensions of
      insight and personal attitudes on juror decision-making. Participants read trial
      scenarios describing a defendant who is accused of a violent crime and is
      diagnosed with schizophrenia. Assigning a verdict of not criminally responsible
      to the defendant was not influenced by insight, but instead, by supportive
      attitudes of the insanity defense and higher attributions of blame to external
      factors and to psychological factors. These findings highlight the need for
      continued investigation in the area of extra-legal factors that guide legal
      decision-making when defendants have a mental disorder. 

PMID- 26294082
TI  - Differential immune responses in mice infected with the tissue-dwelling nematode
      Trichinella zimbabwensis.
AB  - To improve diagnostic tools, immunotherapies and vaccine development for
      trichinellosis surveillance and control there is a need to understand the host
      immune responses induced during infection with Trichinella zimbabwensis, a tissue
      dwelling nematode. In this study, we sought to determine immune responses induced
      in mice during T. zimbabwensis infection. The parasite strain used (Code ISS1209)
      was derived from a naturally infected crocodile (Crocodylus niloticus) and is the
      main Trichinella species prevalent in southern Africa. Sixty 6- to 8-week-old
      female BALB/c mice were randomly assigned to two equal groups: T. zimbabwensis
      infected (n= 30) and the non-infected control group (n= 30). Levels of serum
      tumour necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), interleukin-4
      (IL-4) as well as parasite-specific IgM, IgG, IgG1, IgG2a, IgG2b and IgG3
      antibody responses were determined using enzyme-linked immunosorbent assay
      (ELISA). The cytokines and antibodies provided information on T-helper 1 (Th1)-
      and Th2-type, T-regulatory and antibody responses. Results showed that during the
      intestinal stage of infection, higher levels of parasite-specific IgM, IgG, IgG1
      (P <  0.05) and IL-10 and TNF-alpha (P <  0.001) were observed in the Trichinella
      infected group compared with the non-infected control group. In the parasite
      establishment and tissue migration phases, levels of IgG1 and IgG3 were elevated
      (P <  0.001), while those of IgM (P <  0.01) declined on days 21 and 35 post
      infection (pi) compared to the enteric phase. Our findings show that distinct
      differences in Th1- and Th2-type and T-regulatory responses are induced during
      the intestinal, tissue migration and larval establishment stages of T.
      zimbabwensis infection. 

PMID- 26294083
TI  - A homologue of vitamin K epoxide reductase in Solanum lycopersicum is involved in
      resistance to osmotic stress.
AB  - Vitamin K epoxide reductase (VKOR) exists widely in the chloroplasts of higher
      plants and plays important roles in redox regulation. However, investigations of
      plant VKOR function have primarily focused on VKOR from Arabidopsis, and
      knowledge concerning this function is therefore quite limited. In this study,
      Solanum lycopersicum was used to study the function of VKOR. Transcription level
      analysis revealed that SlVKOR (S. lycopersicum VKOR) expression was upregulated
      by salt or drought stress. To further investigate the function of SlVKOR in
      plants, we generated sense and antisense transgenic S. lycopersicum homozygotes
      at T2 generation plants. Compared with wild-type (WT) plants, the leaf disks of
      the SlVKOR overexpression plants retained a much higher percentage of chlorophyll
      after salt or drought treatment, whereas the antisense transgenic plants
      displayed an opposite response. The overexpressed plants displayed lower levels
      of H2O2 and superoxide anion radical (O2(.-)) than WT plants, whereas antisense
      plants accumulated considerably more H2O2 and O2(.-). The activities of reactive
      oxygen scavenger enzymes, including superoxide dismutase, peroxidase, ascorbate
      peroxidase and catalase, were consistent with the accumulation of reactive oxygen
      species. Based on these results, we suggest that SlVKOR is involved in resistance
      to salt or drought stress.

PMID- 26294084
TI  - Self-Protection of Electrochemical Storage Devices via a Thermal Reversible Sol
      Gel Transition.
AB  - Thermal self-protected intelligent electrochemical storage devices are fabricated
      using a reversible sol-gel transition of the electrolyte, which can decrease the
      specific capacitance and increase and enable temperature-dependent charging and
      discharging rates in the device. This work represents proof of a simple and
      useful concept, which shows tremendous promise for the safe and controlled power
      delivery in electrochemical devices. 

PMID- 26294085
TI  - Intensity tunable infrared broadband absorbers based on VO2 phase transition
      using planar layered thin films.
AB  - Plasmonic and metamaterial based nano/micro-structured materials enable
      spectrally selective resonant absorption, where the resonant bandwidth and
      absorption intensity can be engineered by controlling the size and geometry of
      nanostructures. Here, we demonstrate a simple, lithography-free approach for
      obtaining a resonant and dynamically tunable broadband absorber based on vanadium
      dioxide (VO2) phase transition. Using planar layered thin film structures, where
      top layer is chosen to be an ultrathin (20 nm) VO2 film, we demonstrate broadband
      IR light absorption tuning (from ~90% to ~30% in measured absorption) over the
      entire mid-wavelength infrared spectrum. Our numerical and experimental results
      indicate that the bandwidth of the absorption bands can be controlled by changing
      the dielectric spacer layer thickness. Broadband tunable absorbers can find
      applications in absorption filters, thermal emitters, thermophotovoltaics and
      sensing. 

PMID- 26294086
TI  - Oral, maxillary, and cranial impalement injury by a crossbow arrow.

PMID- 26294087
TI  - Prognostic influence of spontaneous tumor rupture on hepatocellular carcinoma
      after interval hepatectomy.
AB  - BACKGROUND: Spontaneous tumor rupture (STR) is a life-threatening complication of
      hepatocellular carcinoma (HCC). Yet, interval partial hepatectomy (PH) is
      feasible in selected patients after hemostasis for the rupture event. Little is
      known, however, about the extent of negative prognostic impact STR had on these
      patients after resection. Our aim was to determine the impact of STR on the
      oncologic outcome of interval PH for ruptured HCC, and the prognostic value of
      STR on the current tumor node metastasis (TNM) classification. STUDY DESIGN: From
      1989 to 2010, 84 of 364 patients (23%) with STR received staged PH.
      Clinicopathologic variables associated with STR were identified by logistic
      regression analysis and ruptured tumor size with prognostic impact was determined
      by receiver operating characteristic analysis. Comparison of survival curves was
      performed after stratification by the American Joint Committee on Cancer/TNM, 7th
      edition. RESULTS: Ruptured HCC had substantially worse survival than nonruptured
      tumor (5-year overall survival: 22.3% vs 53.4% P < .001). Anti-HCV status (hazard
      ratio [HR]: 3.225 confidence interval [95% CI]: 1.175-8.847, P = .023), platelet
      count (HR: 1.003, CI 1.0001-1.006, P = .042), tumor size (HR: 1.089, CI 1.025
      1.156, P = .006) and microvascular invasion (HR 2.377, CI 1.255-4.502, P = .008)
      were independently associated with STR. When stratified by the TNM system after
      excluding STR as a component of T-staging, ruptured HCC had worse survival
      outcomes than nonruptured HCC in T1-T2 disease and tumors <=10 cm only. A
      receiver operating characteristic analysis confirmed that STR had no additional
      adverse prognostic impact over other tumor features when size > 10 cm (area under
      curve 0.65, P < .001). CONCLUSION: STR affects the outcome of PH for T1-T2
      disease or tumor <=10 cm only. Assigning all resectable ruptured tumors to T4 may
      overestimate the severity of disease.

PMID- 26294088
TI  - Normothermic extracorporeal liver perfusion for donation after cardiac death
      (DCD) livers.
AB  - BACKGROUND: The susceptibility of extended criteria livers to ischemia
      reperfusion injury is a major obstacle in organ cold preservation. Normothermic
      extracorporeal liver perfusion (NELP) has been investigated to reduce ischemic
      damage, restore physiologic function, and assess viability of the liver prior to
      transplant. The goal of this study is to compare physiological parameters of
      livers maintained continuously on NELP to those preserved in cold solution.
      METHODS: Livers from 9 female landrace pigs were subjected to either 20 minutes
      (W20-NELP), 40 minutes (W40-NELP), or 60 minutes (W60-NELP) of warm ischemia
      followed by 6 hours of NELP followed by a 2-hour NELP evaluation phase. This was
      compared with 3 livers subjected to 40 minutes of warm ischemia time followed by
      6 hours of cold storage (W40-Cold) and a 2-hour NELP evaluation phase. Groups
      were compared with the 2-way analysis of variance test. RESULTS: NELP stabilized
      transaminases accompanied by significant improvement in bile production and
      decline in lactate and INR values in all W-NELP groups. Histologic analysis
      demonstrated significant improvement from 0 hour (mild-to-moderate sinusoidal
      dilation and zone 3 necrosis) to the end of the NELP run (minimal necrosis and
      mild IRI). Comparison of W40-NELP and W40-Cold revealed greater bile production
      and oxygen extraction ratio in W40-NELP. In contrast, markers of cellular and
      functional damage were increased in the W40-Cold group. CONCLUSION: NELP improves
      metabolic and functional parameters of livers with either short or extended warm
      ischemia times compared with livers subjected to comparable cold ischemia times.

PMID- 26294089
TI  - Test-retest reliability and agreement of physical fall risk assessment tools in
      adults with intellectual disabilities.
AB  - BACKGROUND: Physical decline and high rates of inactivity lead to an increased
      risk of falling in the intellectual disability (ID) population. It is important
      therefore to develop interventions to prevent falls and to develop valid and
      reliable assessment tools, which are suitable for use with people with ID.
      Targeting the most important fall risk factors such as strength, balance and gait
      measurement is important, yet there is a paucity of previous research on testing
      the feasibility and reliability of strength, balance and gait assessments with
      people with ID. AIMS: The aims of this study are (i) to describe the test-retest
      reliability and agreement [standard error of measurement (SEM)] of slightly
      adapted fall risk assessments and (ii) to describe the test-retest reliability
      and SEM of these tests in younger and older age groups and mild/moderate and
      severe/profound ID-level groups. METHODS: Residents of a German residential
      facility for people with ID were asked to take part. The study has a test-retest
      design, whereby all participants were tested twice, with 7 days in-between the
      first (T1) and second (T2) testing days. The 'timed up and go', '30-second chair
      stand', 'handgrip' and 'Romberg balance test' were all performed. Intraclass
      correlation coefficient (ICC) (2,1) values and SEM were calculated for the full
      sample, two age groups (split at the age of 60 years) and mild/moderate and
      severe/profound ID-level groups. RESULTS: A total of 37 residents with a mean age
      of 59.3 years (standard deviation = 17.7) performed the tests on both testing
      days. Mainly moderate to excellent ICC values were found for all tests for the
      full sample and in all groups (0.59-0.97). Different SEM values were found for
      full sample and sub-groups. CONCLUSION: Strength, balance and gait assessment
      tools, which are easy to use and understand, were found to be reliable in adults
      with ID. The SEM is most important for interpreting the real effects of an
      intervention. Further analyses will be required to gain more information about
      the SEM in different age groups or ID-level groups.

PMID- 26294091
TI  - Systemic EBV-positive lymphoproliferative disease of childhood.

PMID- 26294090
TI  - Myelodysplastic syndromes: 2015 Update on diagnosis, risk-stratification and
      management.
AB  - DISEASE OVERVIEW: The myelodysplastic syndromes (MDS) are a very heterogeneous
      group of myeloid disorders characterized by peripheral blood cytopenias and
      increased risk of transformation to acute myelogenous leukemia (AML). MDS occurs
      more frequently in older males and in individuals with prior exposure to
      cytotoxic therapy. DIAGNOSIS: Diagnosis of MDS is based on morphological evidence
      of dysplasia upon visual examination of a bone marrow aspirate and biopsy.
      Information obtained from additional studies such as karyotype, flow cytometry,
      or molecular genetics is complementary but not diagnostic. Risk-stratification:
      Prognosis of patients with MDS can be calculated using a number of scoring
      systems. In general, all these scoring systems include analysis of peripheral
      cytopenias, percentage of blasts in the bone marrow, and cytogenetic
      characteristics. The most commonly used system still is probably the
      International Prognostic Scoring System (IPSS). IPSS is being replaced by the new
      revised score IPSS-R. RISK-ADAPTED THERAPY: Therapy is selected based on risk,
      transfusion needs, percent of bone marrow blasts, and more recently cytogenetic
      and mutational profiles. Goals of therapy are different in lower risk patients
      than in higher risk. In lower risk, the goal is to decrease transfusion needs and
      transformation to higher risk disease or AML, as well as to improve survival. In
      higher risk, the goal is to prolong survival. Current available therapies include
      growth factor support, lenalidomide, hypomethylating agents, intensive
      chemotherapy, and allogeneic stem cell transplantation. The use of lenalidomide
      has significant clinical activity in patients with lower risk disease, anemia,
      and a chromosome 5 alteration. 5-Azacitidine and decitabine have activity in
      higher risk MDS. 5-Azacitidine has been shown to improve survival in higher risk
      MDS. A number of new molecular lesions have been described in MDS that may serve
      as new therapeutic targets or aid in the selection of currently available agents.
      Additional supportive care measures may include the use of prophylactic
      antibiotics and iron chelation. Management of progressive or refractory disease:
      At the present time there are no approved interventions for patients with
      progressive or refractory disease particularly after hypomethylating based
      therapy. Options include participation in a clinical trial or cytarabine based
      therapy and stem cell transplantation.

PMID- 26294092
TI  - Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk
      stratification and management.

PMID- 26294093
TI  - Building spatial composite indicators to analyze environmental health
      inequalities on a regional scale.
AB  - BACKGROUND: Reducing health inequalities involves the identification and
      characterization of social and exposure factors and the way they accumulate in a
      given area. The areas of accumulation then allow for prioritization of
      interventions. The present study aims to build spatial composite indicators based
      on the aggregation of environmental, social and health indicators and their inter
      relationships. METHOD: Preliminary work was carried out firstly to homogenize
      spatial coverage, and secondly to study spatial variation of environmental (EI),
      socioeconomic (SI) and health (HI) indicators. The aggregation of the different
      indicators was performed using several methodologies for which results and
      decision-makers' usability were compared. RESULTS: Four methodologies were
      tested: 1) A simple summation of normalized HI, EI and SI indicators (IC), 2) the
      sum of the normalized HI, EI and SI indicators weighted by the first principal
      component of a Principal Component Analysis (IC PCA), 3) the sum of normalized
      and weighted indicators of the first principal component of Local Principal
      Component Analysis (IC LPCA), and 4) the sum of normalized and weighted
      indicators of the first principal component of a Geographically Weighted
      Principal Component Analysis (IC GWPCA). CONCLUSION: The GWPCA is particularly
      adapted to taking into account the spatial heterogeneity and the spatial
      autocorrelation between SI, EI and HI. This approach invalidates the basic
      assumptions of many standard statistical analyses. Where socioeconomic indicators
      present high deprivation and where they are associated with potential modifiable
      health determinants, decision-makers can prioritize these areas for reducing
      inequalities by controlling the socioeconomic and health determinants.

PMID- 26294095
TI  - The impact of dementia on the use of general practitioners among the elderly in
      Norway.
AB  - OBJECTIVE: To assess the use of general practitioners (GPs), in elderly home
      dwelling persons in Norway and explore the impact of cognitive decline, age, and
      living situation. DESIGN: Prospective longitudinal study. SETTING: Data were
      collected from municipalities in four counties in Norway in the period from
      January 2009 to August 2012. SUBJECTS: Home-dwelling persons 70 years of age or
      older, receiving in-home care. MAIN OUTCOME MEASURES: Use of GPs over a period of
      18 months related to cognitive state, functional status, neuropsychiatric
      symptoms, and demographics. RESULTS: A total of 599 persons were included. The
      mean annual number of consultations per participant was 5.6 (SD = 5.4). People
      with moderate to severe dementia had fewer consultations per year compared with
      those with mild or no dementia (3.7 versus 5.8 per year, p = 0.004). In the
      multivariate model higher age predicted fewer consultations while affective
      neuropsychiatric symptoms were associated with an increase in frequency of
      consultations. The most frequent reason to consult a GP was cardiovascular
      diseases (36.8% of all consultations), followed by musculoskeletal complaints
      (12.1%) and psychiatric diagnoses (8.7%). CONCLUSION: Our study shows that the
      home-dwelling elderly with moderate to severe dementia in Norway consult their GP
      less often than persons with mild or no dementia. This could indicate a need for
      better interaction between the municipal care and social services and the general
      practitioners.

PMID- 26294094
TI  - Targeted Resequencing of 29 Candidate Genes and Mouse Expression Studies
      Implicate ZIC3 and FOXF1 in Human VATER/VACTERL Association.
AB  - The VATER/VACTERL association describes the combination of congenital anomalies
      including vertebral defects, anorectal malformations, cardiac defects,
      tracheoesophageal fistula with or without esophageal atresia, renal
      malformations, and limb defects. As mutations in ciliary genes were observed in
      diseases related to VATER/VACTERL, we performed targeted resequencing of 25
      ciliary candidate genes as well as disease-associated genes (FOXF1, HOXD13, PTEN,
      ZIC3) in 123 patients with VATER/VACTERL or VATER/VACTERL-like phenotype. We
      detected no biallelic mutation in any of the 25 ciliary candidate genes; however,
      identified an identical, probably disease-causing ZIC3 missense mutation
      (p.Gly17Cys) in four patients and a FOXF1 de novo mutation (p.Gly220Cys) in a
      further patient. In situ hybridization analyses in mouse embryos between E9.5 and
      E14.5 revealed Zic3 expression in limb and prevertebral structures, and Foxf1
      expression in esophageal, tracheal, vertebral, anal, and genital tubercle
      tissues, hence VATER/VACTERL organ systems. These data provide strong evidence
      that mutations in ZIC3 or FOXF1 contribute to VATER/VACTERL. 

PMID- 26294096
TI  - An evaluation of Snoezelen((r)) compared to 'common best practice' for allaying
      the symptoms of wandering and restlessness among residents with dementia in aged
      care facilities.
AB  - Snoezelen has become an increasingly popular therapy in residential aged care
      facilities in Australia and elsewhere, despite no conclusive evidence of its
      clinical efficacy. This paper reports on an evaluation of the use of Snoezelen
      compared to 'common best practice' for allaying the dementia related behaviors of
      wandering and restlessness in two residential aged care facilities in Victoria,
      Australia. Sixteen residents had their behavior and responses to Snoezelen or
      'common best practice' observed and recorded over three time periods. The
      Wilcoxon signed-rank test showed there was a significant improvement in behaviors
      immediately after the intervention and after 60 min. However, no significant
      differences were found between residents receiving Snoezelen and 'common best
      practice' interventions for the reduction of the dementia related behaviors. 

PMID- 26294097
TI  - The MEPPP Framework: A Framework for Monitoring and Evaluating Participatory
      Planning Processes.
AB  - Evaluating participatory processes, participatory planning processes especially,
      can be challenging. Due to their complexity, these processes require a specific
      approach to evaluation. This paper proposes a framework for evaluating projects
      that have adopted a participatory planning approach: the monitoring and
      evaluation of participatory planning processes (MEPPP) framework. The MEPPP
      framework is applied to one case study, a participatory planning process in the
      Rwenzori region in Uganda. We suggest that this example can serve as a guideline
      for researchers and practitioners to set up the monitoring and evaluation of
      their participatory planning process of interest by following six main phases:
      (1) description of the case, (2) clarification of the M&E viewpoint(s) and
      definition of the M&E objective(s), (3) identification of the context, process
      and outputs/outcomes analytical variables, (4) development of the M&E methods and
      data collection, (5) data analysis, and (6) sharing of the M&E results. Results
      of the application of the MEPPP framework in Uganda demonstrate the ability of
      the framework to tackle the complexity of participatory planning processes.
      Strengths and limitations of the MEPPP framework are also discussed. 

PMID- 26294098
TI  - Chinese EFL teachers' knowledge of basic language constructs and their self
      perceived teaching abilities.
AB  - The present study examined the knowledge and skills of basic language constructs
      among elementary school teachers who were teaching English as a Foreign Language
      (EFL) in China. Six hundred and thirty in-service teachers completed the adapted
      Reading Teacher Knowledge Survey. Survey results showed that English teachers'
      self-perceived ability to teach vocabulary was the highest and self-perceived
      ability to teach reading to struggling readers was the lowest. Morphological
      knowledge was positively correlated with teachers' self-perceived teaching
      abilities, and it contributed unique variance even after controlling for the
      effects of ultimate educational attainment and years of teaching. Findings
      suggest that elementary school EFL teachers in China, on average, were able to
      display implicit skills related to certain basic language constructs, but less
      able to demonstrate explicit knowledge of other skills, especially sub-lexical
      units (e.g., phonemic awareness and morphemes). The high self-perceived ability
      of teaching vocabulary and high scores on syllable counting reflected the focus
      on larger units in the English reading curriculum.

PMID- 26294100
TI  - Antifungal modes of action of tea tree oil and its two characteristic components
      against Botrytis cinerea.
AB  - AIMS: The essential oil of Melaleuca alternifolia (tea tree) has been evaluated
      as a potential eco-friendly antifungal agent against Botrytis cinerea. In this
      study, we investigated the antifungal activity and mode of action of tea tree oil
      (TTO) and its components against B. cinerea. METHODS AND RESULTS: Of the
      components we tested in contact phase, terpinen-4-ol had the highest antifungal
      activity, followed by TTO, alpha-terpineol, terpinolene, then 1,8-cineole. As one
      of characteristic components of TTO, terpinen-4-ol treatment led to pronounced
      alterations in mycelial morphology, cellular ultrastructure, membrane
      permeability under scanning electron microscope, transmission electron microscope
      and fluorescent microscope, and also reduced the ergosterol content of fungi. As
      another characteristic component, 1,8-cineole caused serious intracellular damage
      but only slightly affected B. cinerea otherwise. When terpinen-4-ol and 1,8
      cineole were used together, the synergistic antifungal activity was significantly
      higher than either component by itself. CONCLUSIONS: The results of our study
      confirmed that terpinen-4-ol and 1,8-cineole act mainly on the cell membranes and
      organelles of B. cinerea, respectively, and when combined are similar to TTO in
      antifungal activity due to their differences. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Understanding the mechanism of terpinen-4-ol and 1,8-cineole antifungal
      action to B. cinerea is helpful for investigation on their synergistic effect and
      explaining antifungal action modes of TTO.

PMID- 26294099
TI  - Inactivation of tumor suppressor gene pten in early and advanced gallbladder
      cancer.
AB  - BACKGROUND: PTEN is a tumor suppressor gene that regulates the PTEN/PI3k/AKT/mTOR
      pathway, which is frequently altered in human cancers including gallbladder
      cancer (GBC). To determine the frequency of PTEN expression in GBC and to
      establish its relation to clinical and morphological parameters and survival in
      GBC. METHODS: The immunohistochemical expression of PTEN was studied in 108 GBC.
      All the cases included areas of non-tumor mucosa adjacent to the tumor. RESULTS:
      The group was comprised of 108 patients, 91 women (84.3%) and 17 men (15.7%) with
      an average age of 65.2 years (SD +/- 12.3 years). Thirty-five cases (33%) were
      early carcinomas (EC) and the remaining 73 (67%) were advanced cases (AC). All
      the internal controls were positive (moderate or intense in 96.3%). Only in three
      AC (4.1%) was there a complete absence of PTEN immunohistochemical expression.
      There were no significant differences in relation between PTEN expression and
      tumor infiltration or degree of differentiation. The three patients with PTEN
      inactivation died before 10 months; however, the other patients with AC had a
      survival of 53% at 10 months. DISCUSSION: Loss of PTEN expression was observed in
      4.1% of the advanced GBC. All the patients with this alteration died before 10
      months. PTEN inactivation could be a rare event, but with a poor prognosis in
      advanced GBC.

PMID- 26294101
TI  - Pars plana vitrectomy with juxtapapillary laser photocoagulation versus
      vitrectomy without juxtapapillary laser photocoagulation for the treatment of
      optic disc pit maculopathy: the results of the KKESH International Collaborative
      Retina Study Group.
AB  - BACKGROUND/AIMS: To compare the functional and anatomic outcomes of pars plana
      vitrectomy (PPV) with juxtapapillary laser photocoagulation (JLP) versus
      vitrectomy without JLP in optic disc pit maculopathy. METHODS: This was a
      multicentre, retrospective study of 46 consecutive patients with optic disc pit
      maculopathy presenting at tertiary eye centres between 1992 and 2012. Indications
      for surgery included distorted or decreased vision. Surgical intervention
      included PPV, posterior vitreous detachment, with or without gas tamponade.
      Twenty-four patients received laser photocoagulation at the temporal edge of the
      optic disc pit (group A) and 22 patients had no laser (group B). Postoperative
      best-corrected visual acuity (BCVA) and optical coherence tomography findings
      were the main outcome measures. RESULTS: Mean follow-up was 44 months (range 12
      98 months). BCVA in group A improved significantly from 0.7 logMAR (20/100)
      preoperatively to 0.5 logMAR (20/60) postoperatively (p=0.017). In group B, BCVA
      improved from 0.7 logMAR (20/100) preoperatively to 0.4 logMAR (20/40)
      postoperatively (p=0.014). The difference in final BCVA between groups was not
      statistically significant (p=0.693). The mean central macular thickness (CMT) in
      group A improved significantly from 750 MUm preoperatively to 309 MUm at last
      follow-up (p<0.0001). The mean CMT in group B improved from 616 MUm
      preoperatively to 291 MUm at last follow-up (p=0.028). The difference in final
      CMT between groups was not statistically significant (p=0.747). CONCLUSIONS: PPV
      with JLP for optic disc pit maculopathy had similar functional and anatomic
      outcomes compared with vitrectomy without JLP.

PMID- 26294102
TI  - Anterior segment morphology after acute primary angle closure treatment: a
      randomised study comparing iridoplasty and medical therapy.
AB  - PURPOSE: To compare the effect of argon laser peripheral iridoplasty (ALPI) and
      conventional medical therapy in the immediate treatment of acute primary angle
      closure (APAC) using anterior segment optical coherence tomography (ASOCT).
      METHODS: In this single tertiary centre, prospective comparative study, we
      randomised 30 consecutive patients with unilateral APAC into two groups: ALPI and
      medical treatment (n=15 each). Immediately before and 1 h after either
      intervention, ASOCT imaging was performed. Custom software was used to measure
      pupil diameter, anterior chamber depth, iris curvature (I-Curv), iris area (I
      Area), and the angle opening distance (AOD750), trabecular iris space area
      (TISA750) and the iris thickness at 750 um from the scleral spur. The main
      outcome measure was the change in anterior segment biometrical parameters.
      RESULTS: The mean age of the patients was 62.8+/-7.7 years; 13 (43.3%) were male.
      APAC eyes treated with ALPI had a larger increase in AOD750 (p=0.002) and TISA750
      (p=0.006); a smaller increase in I-Area (p=0.004) and a decrease in I-Curv
      (p=0.001) after treatment compared with those eyes which received medical
      therapy. An optimal model consisting of age, gender, pretreatment and post
      treatment pupil diameter, treatment modality and pretreatment I-Curv explained
      53.2% of the variance in AOD750 change after treatment, with the treatment
      modality accounting for 35.0% and I-Curv accounting for 12.4% of the variability.
      CONCLUSIONS: We observed a greater increase in angle width after ALPI compared
      with after medical treatment in eyes with APAC. Treatment modality and
      pretreatment I-Curv were the most significant predictors of angle width change
      after treatment.

PMID- 26294103
TI  - C21orf2 is mutated in recessive early-onset retinal dystrophy with macular
      staphyloma and encodes a protein that localises to the photoreceptor primary
      cilium.
AB  - BACKGROUND/AIM: We have noted a phenotype of early-onset retinal dystrophy with
      macular staphyloma but without high myopia. The aim of this study is to report
      the underlying genetic mutations and the subcellular localisation of the gene
      product in the retina. METHODS: Retrospective case series (2012-2015);
      immunohistochemical analyses of mammalian retina for in situ protein
      localisation. RESULTS: All three probands were first noted to have decreased
      vision at 3-6 years old which worsened over time. At ages 39, 37 and 12 years
      old, all had similar retinal findings: dystrophic changes (retinal pigment
      epithelium mottling, vessel narrowing), macular staphyloma (despite only mild
      myopia or high hyperopia), and non-recordable electroretinography. All harboured
      homozygous mutations in C21orf2, a gene recently suggested to be associated with
      retinal dystrophy but of unknown function. Two had a frameshift deletion
      c.436_466del (p.Glu146Serfs*6). The third had a missense mutation affecting a
      highly conserved residue (p.Cys61Tyr) and was short (below the 3rd percentile)
      and obese (50th percentile for weight despite short stature). Immunohistochemical
      studies in human, pig and mouse retinas localised C21orf2 protein to the ciliary
      structures of the photoreceptor cell (the daughter basal body, the centriole
      adjacent to the basal body, and the connecting cilium). CONCLUSIONS: This retinal
      dystrophy phenotype is caused by recessive mutations in C21orf2 and can be
      considered a retinal ciliopathy as C21orf2 encodes a protein that localises to
      photoreceptor ciliary structures. The short stature and obesity noted in the
      youngest girl suggest that for some patients biallelic C21orf2 mutations may
      result in syndromic ciliopathy.

PMID- 26294104
TI  - New associations of classic acute macular neuroretinopathy.
AB  - PURPOSE: To describe novel underlying associations of classic acute macular
      neuroretinopathy (AMN). METHODS: Multimodal imaging case series evaluating
      patients with classic AMN lesions and previously unreported underlying
      aetiologies. RESULTS: Six patients were included (five women, one man, mean age
      30+/-7 years). Mean distance best corrected visual acuity at initial presentation
      was 0.21+/-0.3 logMAR (mean Snellen acuity: 20/30, range 20/15-20/100) and at
      last follow-up visit 0.09+/-0.17 logMAR (Snellen acuity: 20/20, range 20/15
      20/60). All cases but one had bilateral lesions and showed typical parafoveal
      hyporeflective lesions on infrared imaging, which corresponded to the hyper
      reflectivity in the Henle's layer with attenuation of the external limiting
      membrane, the ellipsoid zone and interdigitation zone. Underlying diseases
      included thrombocytopenia and anaemia associated with dengue fever, acute
      lymphoblastic leukaemia, chronic kidney disease and ulcerative colitis, while
      Valsalva-like manoeuvre was found to be a potential trigger. Other novel
      associations included the use of lisdexamphetamine. CONCLUSIONS: Classic AMN may
      be associated with leukaemia, dengue fever, ulcerative colitis and chronic kidney
      disease, probably as a result of chorioretinal hypoxia in the setting of
      thrombocytopenia and anaemia. Adrenergic agonists such as lisdexamphetamine may
      also contribute to the manifestation of AMN.

PMID- 26294105
TI  - Risk of optic pathway glioma in children with neurofibromatosis type 1 and optic
      nerve tortuosity or nerve sheath thickening.
AB  - BACKGROUND/AIMS: Optic nerve tortuosity and nerve and sheath thickening are
      observed on MRI in some patients with neurofibromatosis type 1 (NF-1). This study
      aimed to determine if tortuosity and thickening are associated with the
      development of optic pathway glioma (OPG) and subsequent vision loss. METHODS:
      Children with NF-1 who underwent brain MRI between 1992 and 2005, and had at
      least 1 year of subsequent visual acuity (VA) follow-up, were identified
      retrospectively. The baseline MRI was independently reviewed by three
      neuroradiologists for consensus assessment. Tortuosity was identified using
      validated operational criteria. Optic nerve and sheath thicknesses and VA at last
      follow-up were directly measured. RESULTS: Of 132 evaluable children, seven (5%)
      had tortuosity on baseline MRI. 20 subjects (15%) ultimately developed OPG at a
      median of 1.9 years (range 7 months-8.0 years) following the baseline MRI.
      Subjects with tortuosity were significantly more likely to develop OPG than those
      without tortuosity (57% vs 13%, p=0.01). In subjects who developed OPG, the
      prevalence of tumour-related vision loss was not significantly different between
      those with and without baseline tortuosity (14% vs 4%, p=0.28). No difference
      existed between mean baseline optic nerve (2.3 vs 2.2 mm) or sheath (5.2 vs 5.4
      mm) thicknesses comparing subjects who did and did not develop OPG. CONCLUSIONS:
      Optic nerve tortuosity at baseline is associated with OPG development among
      patients with NF-1, but does not predispose to aggressive OPG with associated
      vision loss. Neither nerve nor sheath thickening at baseline is associated with
      OPG development.

PMID- 26294106
TI  - Management of advanced corneal ectasias.
AB  - Corneal ectasias include a group of disorders characterised by progressive
      thinning, bulging and distortion of the cornea. Keratoconus is the most common
      disease in this group. Other manifestations include pellucid marginal
      degeneration, Terrien's marginal degeneration, keratoglobus and ectasias
      following surgery. Advanced ectasias usually present with loss of vision due to
      high irregular astigmatism. Management of these disorders is difficult due to the
      peripheral location of ectasia and associated severe corneal thinning. Newer
      contact lenses such as scleral lenses are helpful in a selected group of
      patients. A majority of these cases requires surgical intervention. This review
      provides an update on the current treatment modalities available for management
      of advanced corneal ectasias. 

PMID- 26294107
TI  - Histological features of Cytomegalovirus-related corneal graft infections, its
      associated features and clinical significance.
AB  - AIM: To describe the histological features of ITALIC! Cytomegalovirus (CMV)
      related corneal graft infections, its associated features and clinical
      significance. METHODS: This was a retrospective histological study of 48
      consecutive cases of failed repeat penetrating keratoplasty cases with a clinical
      diagnosis of allograft rejection from 2011 to 2013. CMV infection was confirmed
      with CMV antibody immunohistochemistry (IHC) and electron microscopy. Additional
      CD163 and CD68 IHCs for macrophages were also performed. Clinical data and
      previous graft histology were then reviewed. RESULTS: Mean incidence of CMV
      infection in corneal graft rejection buttons was 6.3% per year. 3/48 graft
      buttons were CMV antibody positive. Histological features of CMV graft infection
      include: (1) stromal keratocytes with cytopathic changes; (2) lack of
      inflammation, only occasional macrophages present and (3) absence of
      vascularisation. None of the patients had a history of active CMV infection.
      CONCLUSION: CMV infection is not limited as endotheliitis, but extends into the
      corneal stroma, and is a potential reservoir for graft infection, especially in
      partial thickness endothelial surgery. Clinical features are often non-specific,
      although glaucoma was present in our patients. CMV-infected grafts showed CD163
      positive M2 macrophages in close association with the infected keratocytes,
      suggesting that the macrophage may be important in CMV graft infection.
      Histological examination with CMV IHC is a useful method to detect CMV infection
      postoperatively. Post penetrating keratoplasty, CMV systemic treatment with
      valganciclovir can prevent graft infection and failure. Boston keratoprosthesis
      may be a potential alternative surgery in active CMV infections that obviates the
      need for systemic therapy.

PMID- 26294109
TI  - Stratifying Risk for Renal Insufficiency Among Lithium-Treated Patients: An
      Electronic Health Record Study.
AB  - Although lithium preparations remain first-line treatment for bipolar disorder,
      risk for development of renal insufficiency may discourage their use. Estimating
      such risk could allow more informed decisions and facilitate development of
      prevention strategies. We utilized electronic health records from a large New
      England health-care system between 2006 and 2013 to identify patients aged 18
      years or older with a lithium prescription. Renal insufficiency was identified
      using the presence of renal failure by ICD9 code or laboratory-confirmed
      glomerular filtration rate below 60 ml/min. Logistic regression was used to build
      a predictive model in a random two-thirds of the cohort, which was tested in the
      remaining one-third. Risks associated with aspects of pharmacotherapy were also
      examined in the full cohort. We identified 1445 adult lithium-treated patients
      with renal insufficiency, matched by risk set sampling 1 : 3 with 4306 lithium
      exposed patients without renal insufficiency. In regression models, features
      associated with risk included older age, female sex, history of smoking, history
      of hypertension, overall burden of medical comorbidity, and diagnosis of
      schizophrenia or schizoaffective disorder (p<0.01 for all contrasts). The model
      yielded an area under the ROC curve exceeding 0.81 in an independent testing set,
      with 74% of renal insufficiency cases among the top two risk quintiles. Use of
      lithium more than once daily, lithium levels greater than 0.6 mEq/l, and use of
      first-generation antipsychotics were independently associated with risk. These
      results suggest the possibility of stratifying risk for renal failure among
      lithium-treated patients. Once-daily lithium dosing and maintaining lower lithium
      levels where possible may represent strategies for reducing risk.

PMID- 26294110
TI  - Saccharothrix lopnurensis sp. nov., a filamentous actinomycete isolated from
      sediment of Lop Nur.
AB  - A novel actinomycete strain, designated YIM LPA2h(T), was isolated from a
      sediment sample collected from Lop Nur, Xinjiang Uygur Autonomous Region, North
      West China. The taxonomic position of strain YIM LPA2h(T) was investigated by a
      polyphasic approach. The morphological and chemotaxonomic properties of the
      isolate were in accordance with the members of the genus Saccharothrix. The 16S
      rRNA gene sequence of the strain showed highest similarities to Saccharothrix
      yanglingensis (98.6 %), Saccharothrix longispora (98.4 %) and Saccharothrix
      hoggarensis (98.3 %). However, the DNA-DNA hybridization values between the new
      isolate YIM LPA2h(T) and S. yanglingensis, S. longispora and S. hoggarensis were
      significantly below 70 %. Strain YIM LPA2h(T) was found to contain meso
      diaminopimelic acid as diagnostic diamino acid. The major sugars in whole-cell
      hydrolysates were rhamnose, galactose, mannose, glucose and fructose. The major
      polar lipids were identified as phosphatidylethanolamine,
      phosphatidylhydroxylethanolamine, diphosphatidylglycerol, phosphatidylinositol
      and phosphatidylinositol mannoside. The predominant respiratory menaquinones were
      MK-9 (H4) and MK-10 (H4). The major fatty acids were C17:1 omega8c (15 %), iso
      C15:0 (12 %), anteiso-C15:0 (12 %) and summed feature 3 (C16:1 omega6c/C16:1
      omega7c, 10 %). The genomic DNA G+C content of strain YIM LPA2h(T) was determined
      to be 75 mol %. The genotypic and phenotypic results suggest that strain YIM
      LPA2h(T) represents a novel species of the genus Saccharothrix, for which the
      name Saccharothrix lopnurensis sp. nov. is proposed. The type strain is YIM
      LPA2h(T) (=CGMCC 4.7246(T)=KCTC 39545(T)).

PMID- 26294108
TI  - Neuroimaging of Fear-Associated Learning.
AB  - Fear conditioning has been commonly used as a model of emotional learning in
      animals and, with the introduction of functional neuroimaging techniques, has
      proven useful in establishing the neurocircuitry of emotional learning in humans.
      Studies of fear acquisition suggest that regions such as amygdala, insula,
      anterior cingulate cortex, and hippocampus play an important role in acquisition
      of fear, whereas studies of fear extinction suggest that the amygdala is also
      crucial for safety learning. Extinction retention testing points to the
      ventromedial prefrontal cortex as an essential region in the recall of the safety
      trace, and explicit learning of fear and safety associations recruits additional
      cortical and subcortical regions. Importantly, many of these findings have
      implications in our understanding of the pathophysiology of psychiatric disease.
      Recent studies using clinical populations have lent insight into the changes in
      regional activity in specific disorders, and treatment studies have shown how
      pharmaceutical and other therapeutic interventions modulate brain activation
      during emotional learning. Finally, research investigating individual differences
      in neurotransmitter receptor genotypes has highlighted the contribution of these
      systems in fear-associated learning. 

PMID- 26294111
TI  - Genetic, immune and vasoactive factors in the vascular dysfunction associated
      with hypertension in pregnancy.
AB  - INTRODUCTION: Preeclampsia (PE) is a major complication of pregnancy that could
      lead to maternal and fetal morbidity and mortality. The pathophysiological
      mechanisms of PE are not completely understood, but recent research has begun to
      unravel some of the potential mechanisms. AREAS COVERED: Genetic polymorphisms
      and altered maternal immune response may cause impaired remodeling of the spiral
      arteries; a potential early defect in PE. Inadequate invasion of cytotrophoblasts
      into the decidua leads to reduced uteroplacental perfusion pressure (RUPP) and
      placental ischemia/hypoxia. Placental ischemia causes the release of biologically
      active factors such as anti-angiogenic factors, inflammatory cytokines, reactive
      oxygen species, hypoxia-inducible factors, and angiotensin II receptor
      autoantibodies. These vasoactive factors could cause systemic vascular
      endotheliosis and consequent increase in vascular resistance and blood pressure,
      glomerular endotheliosis causing proteinuria, cerebrovascular endotheliosis
      causing cerebral edema, seizures and visual disturbances, and hepatic
      endotheliosis, which may contribute to the manifestations of HELLP syndrome. PE
      associated vascular endotheliosis causes a decrease in vasodilator mediators such
      as nitric oxide, prostacyclin and endothelium-derived hyperpolarizing factor, an
      increase in vasoconstrictors such as endothelin-1, angiotensin II and thromboxane
      A2, and enhanced mechanisms of vascular smooth muscle contraction such as
      intracellular Ca(2+), protein kinase C and Rho-kinase. Changes in matrix
      metalloproteinase activity and extracellular matrix cause vascular remodeling and
      further vasoconstriction. EXPERT OPINION: Some of the genetic, immune and
      vasoactive factors involved in vascular endotheliosis could be used as biomarkers
      for early detection, and as potential targets for prevention and treatment of PE.

PMID- 26294112
TI  - Cross-platform assessment of genomic imbalance confirms the clinical relevance of
      genomic complexity and reveals loci with potential pathogenic roles in diffuse
      large B-cell lymphoma.
AB  - Genomic copy number alterations (CNAs) in diffuse large B-cell lymphoma (DLBCL)
      have roles in disease pathogenesis, but overall clinical relevance remains
      unclear. Herein, an unbiased algorithm was uniformly applied across three genome
      profiling datasets comprising 392 newly-diagnosed DLBCL specimens that defined 32
      overlapping CNAs, involving 36 minimal common regions (MCRs). Scoring criteria
      were established for 50 aberrations within the MCRs while considering peak
      gains/losses. Application of these criteria to independent datasets revealed
      novel candidate genes with coordinated expression, such as CNOT2, potentially
      with pathogenic roles. No one single aberration significantly associated with
      patient outcome across datasets, but genomic complexity, defined by imbalance in
      more than one MCR, significantly portended adverse outcome in two of three
      independent datasets. Thus, the standardized scoring of CNAs currently developed
      can be uniformly applied across platforms, affording robust validation of genomic
      imbalance and complexity in DLBCL and overall clinical utility as biomarkers of
      patient outcome. 

PMID- 26294113
TI  - Epitope analysis of antidesmoglein 1 autoantibodies from patients with pemphigus
      foliaceus across different activity stages.
AB  - BACKGROUND: Pemphigus foliaceus (PF) and pemphigus vulgaris (PV) are closely
      related, but clinically distinct, autoimmune blistering diseases caused by
      autoantibodies against desmoglein (Dsg)1 and Dsg3, respectively. Using
      ethylenediaminetetraacetic acid (EDTA)-treated Dsg3 enzyme-linked immunosorbent
      assay (ELISA) we have shown that the proportion of anti-Dsg3 antibodies against
      calcium-dependent epitopes decreased upon shifting to the inactive phase in
      patients with PV. OBJECTIVES: To analyse the epitope profiles of anti-Dsg1
      antibodies across the different activity stages of PF. METHODS: We evaluated five
      patients with PF who retained high serum levels of anti-Dsg1 antibodies in the
      inactive phase. Sera were obtained in both the active and inactive phases, and
      were analysed by EDTA-treated and exfoliative toxin-treated ELISAs. To map the
      epitopes of anti-Dsg1 antibodies, immunoprecipitation-immunoblotting was
      performed using a set of Dsg1/Dsg2 domain-swapped molecules. RESULTS: Anti-Dsg1
      antibodies against the calcium-dependent epitopes of Dsg1 were the predominant
      antibodies in both the active and inactive phases. The proportion of anti-Dsg1
      antibodies against the calcium-dependent epitopes did not change upon shifting to
      the inactive phase. The results of immunoprecipitation-immunoblotting showed that
      most of the anti-Dsg1 antibodies bound to the extracellular domains (EC)1-2 of
      Dsg1. CONCLUSIONS: In patients with PF, the calcium-dependent epitopes on EC1 and
      EC2 of Dsg1 contained definitively pathogenic and nonpathogenic epitopes. The
      disease activity might be differentially controlled by the antibodies between PF
      and PV depending on the presence or absence of the nonpathogenic epitope.

PMID- 26294114
TI  - Long-term healthy lifestyle patterns and tooth loss studied in a Swedish cohort
      of middle-aged and older people.
AB  - The promotion of a healthy lifestyle has become an issue of public health
      importance in the context of ageing populations and increasing prevalence of
      chronic diseases. OBJECTIVE: (i) To estimate changes in use of fluoridated tooth
      paste, use of tooth picks, smoking and alcohol consumption and (ii) to examine
      whether experience with incident or prevalent tooth loss predict healthy
      lifestyle transitions from age 50 to 70. METHOD: In 1992, 6346 individuals born
      in 1942 agreed to participate in a prospective cohort study and 3585 completed
      follow-up questionnaires in 1997, 2002, 2007 and 2012. Statistical analyses were
      conducted by chi-square statistics, Cochran's Q and logistic regression. RESULTS:
      In total, 15.7% and 74.0% reported incident (tooth loss only in 2012) and
      prevalent tooth loss (tooth loss in 1992 and 2012). Significant differences
      occurred between the 1992 and 2012 prevalence of using toothpicks (from 48.3% to
      69.1%), smoking (from 26.9% to 10.1%) and alcohol consumption (from 41.5% to
      50.5%), 29% and 15.6% increased use of toothpicks and alcohol consumption,
      whereas 15.5% stopped daily smoking. Increased use of fluoridated tooth paste,
      smoking cessation and failure to increase use of toothpicks was associated with
      prevalent tooth loss between age 50 and 70. CONCLUSION: This study revealed
      positive and negative trends in oral health behaviours over a 20-year period in
      persons aged 50 at baseline. Mixed support was obtained for the assumption that
      oral health promoting lifestyle transitions follow experience with tooth loss.
      Older people with tooth loss experience could benefit from targeted counselling
      aimed at coping with oral diseases.

PMID- 26294115
TI  - Chromatin in 3D: progress and prospects for plants.
AB  - Methods that use high-throughput sequencing have begun to reveal features of the
      three-dimensional structure of genomes at a resolution that goes far beyond that
      of traditional microscopy. Integration of these methods with other molecular
      tools has advanced our knowledge of both global and local chromatin packing in
      plants, and has revealed how patterns of chromatin packing correlate with the
      genomic and epigenomic landscapes. This update reports recent progress made in
      this area in plants, and suggests new research directions. 

PMID- 26294133
TI  - Population genetic diversity and hybrid detection in captive zebras.
AB  - Zebras are members of the horse family. There are three species of zebras: the
      plains zebra Equus quagga, the Grevy's zebra E. grevyi and the mountain zebra E.
      zebra. The Grevy's zebra and the mountain zebra are endangered, and hybridization
      between the Grevy's zebra and the plains zebra has been documented, leading to a
      requirement for conservation genetic management within and between the species.
      We characterized 28 microsatellite markers in Grevy's zebra and assessed cross
      amplification in plains zebra and two of its subspecies, as well as mountain
      zebra. A range of standard indices were employed to examine population genetic
      diversity and hybrid populations between Grevy's and plains zebra were simulated
      to investigate subspecies and hybrid detection. Microsatellite marker
      polymorphism was conserved across species with sufficient variation to enable
      individual identification in all populations. Comparative diversity estimates
      indicated greater genetic variation in plains zebra and its subspecies than
      Grevy's zebra, despite potential ascertainment bias. Species and subspecies
      differentiation were clearly demonstrated and F1 and F2 hybrids were correctly
      identified. These findings provide insights into captive population genetic
      diversity in zebras and support the use of these markers for identifying hybrids,
      including the known hybrid issue in the endangered Grevy's zebra. 

PMID- 26294134
TI  - Changes of Cardiac Function During Ultradistance Trail Running.
AB  - Previous studies have noted reversible cardiac dysfunction during marathon races,
      but few data are available concerning ultradistance trail running. The aim of
      this study was to assess echocardiographic parameters during ultradistance trail
      running. We performed an observational study in 66 participants to the 80-km
      Ecotrail of Paris Ile de France. All subjects had echocardiographic examinations
      before the race and on arrival, and 28 of them underwent serial echocardiographic
      examinations during the race (21 and 53 km). A single experienced physician
      performed all echocardiographic examinations, and the same protocol was always
      used (conventional 2-dimensional and Doppler left ventricular parameters and
      longitudinal strain). All echocardiographic parameters of left ventricular (LV)
      systolic function were significantly decreased on arrival (p <=0.002). A
      significant reduction of LV systolic function was observed in 48% of study
      subjects on arrival. No significant modification was observed at 21 or at 53 km,
      and only global longitudinal strain was significantly decreased (p = 0.0008). At
      arrival, mitral E/A ratio and average mitral tissue Doppler imaging e' wave were
      significantly decreased (p = 0.0001 and p = 0.0004, respectively), but these
      changes were observed from 21 km. In conclusion, ultradistance trail running can
      lead to abnormalities of LV systolic and diastolic functions in amateur runners.
      Diastolic dysfunction arises earlier than systolic dysfunction. Left ventricular
      systolic dysfunction occurred in 48% of the study subjects and was detected early
      by assessment of longitudinal strain. 

PMID- 26294135
TI  - Computed Tomographic and Morphologic Features of Syphilis of the Aorta.
AB  - This report describes certain computed tomographic and morphologic features of
      syphilitic aortitis in 2 patients in whom the process involved the entire
      thoracic aorta. 

PMID- 26294136
TI  - The Effects of Dextromethorphan on Driving Performance and the Standardized Field
      Sobriety Test.
AB  - Dextromethorphan (DXM) is abused most commonly among adolescents as a
      recreational drug to generate a dissociative experience. The objective of the
      study was to assess driving with and without DXM ingestion. The effects of one
      time maximum daily doses of DXM 120 mg versus a guaifenesin 400 mg dose were
      compared among 40 healthy subjects using a crossover design. Subjects' ability to
      drive was assessed by their performance in a driving simulator (STISIM(r) Drive
      driving simulator software) and by conducting a standardized field sobriety test
      (SFST) administered 1-h postdrug administration. The one-time dose of DXM 120 mg
      did not demonstrate driving impairment on the STISIM(r) Drive driving simulator
      or increase SFST failures compared to guaifenesin 400 mg. Doses greater than the
      currently recommended maximum daily dose of 120 mg are necessary to perturb
      driving behavior.

PMID- 26294137
TI  - Parkinson's disease (PD) with dementia and falls is improved by AChEI? A
      preliminary study report.
AB  - BACKGROUND/OBJECTIVE: Advanced PD is often associated with cognitive impairment
      and frequent falls. We describe a suggestive case report of PD associated with
      mild cognitive impairment (MCI) and falls. The aim of our study was to test
      alteration in balance potentially related to use of acetylcholinesterase
      inhibitor (AchEI). We address this hypothesis after keeping the patient in stable
      dosage of dopamine agonist. METHODS/MEASUREMENTS: We describe an initial
      pharmacological management in a 78-year-old man affected by Parkinson disease
      (PD) associated with mild cognitive impairment (MCI) and history of falls. The
      diagnosis of PD was also confirmed by SPECT with DATSCAN, after CT-brain
      exclusion of potential other causes of the symptoms. Cognitive and motor
      performances of the patient were initially evaluated by Mini Mental Examination
      State Examination (MMSE), Short Physical Performance Battery (SPPB) and Romberg
      test. We also recorded gait parameters using an accelerometer, while balance and
      stability were assessed by stabilometric platform with open and closed eyes. We
      repeated cognitive and motor tests and gait and balance evaluation after stable
      dosage of dopamine agonist before and after introduction of AchEI. RESULTS: After
      starting dopamine agonist therapy, there was a significant improvement in gait
      parameters (speed, stride/min, stride length, swing duration, and decrease in
      gait cycle duration and rolling duration). When stable dosage of dopamine agonist
      was reached, AchEI was introduced obtaining not only a significant improvement of
      cognitive performance, but also a significant positive change in balance.
      CONCLUSION AND RELEVANCE: We hypothesize that AchEI could improve stability,
      balance and postural instability in addition to cognitive performance in PD with
      MCI and balance deficits.

PMID- 26294139
TI  - Dimension-Controlled Assemblies Comprising pi-Electronic Systems.

PMID- 26294138
TI  - Generalized periodic discharges and 'triphasic waves': A blinded evaluation of
      inter-rater agreement and clinical significance.
AB  - OBJECTIVES: Generalized periodic discharges (GPDs) are associated with
      nonconvulsive seizures. Triphasic waves (TWs), a subtype of GPDs, have been
      described in relation to metabolic encephalopathy and not felt to be associated
      with seizures. We sought to establish the consistency of use of this descriptive
      term and its association with seizures. METHODS: 11 experts in continuous EEG
      monitoring scored 20 cEEG samples containing GPDs using Standardized Critical
      Care EEG Terminology. In the absence of patient information, the inter-rater
      agreement (IRA) for EEG descriptors including TWs was assessed along with raters'
      clinical EEG interpretation and compared with actual patient information.
      RESULTS: The IRA for 'generalized' and 'periodic' was near-perfect (kappa=0.81),
      but fair for 'triphasic' (kappa=0.33). Patients with TWs were as likely to
      develop seizures as those without (25% vs 26%, N.S.) and surprisingly, patients
      with TWs were less likely to have toxic-metabolic encephalopathy than those
      without TWs (55% vs 79%, p<0.01). CONCLUSIONS: While IRA for the terms
      "generalized" and "periodic" is high, it is only fair for TWs. EEG interpreted as
      TWs presents similar risk for seizures as GPDs without triphasic appearance. GPDs
      are commonly associated with metabolic encephalopathy, but 'triphasic' appearance
      is not predictive. SIGNIFICANCE: Conventional association of 'triphasic waves'
      with specific clinical conditions may lead to inaccurate EEG interpretation.

PMID- 26294140
TI  - Improving outpatient care in pediatrics: A challenge.

PMID- 26294141
TI  - Art as an instrument to understand the difference between information, knowledge
      and knowing.

PMID- 26294142
TI  - Prevalence of vulvovaginitis and relation to physical findings in girls assessed
      for suspected child sexual abuse.
AB  - INTRODUCTION: The presence of sexually transmitted infections (STIs) in patients
      with suspected sexual abuse is uncommon in the field of pediatrics. OBJECTIVES:
      To establish the prevalence of anogenital findings and their relation to the
      presence of STIs in girls referred for suspected child sexual abuse. MATERIAL AND
      METHODS: Retrospective study conducted between January 1st, 2003 and December
      31st, 2013. Physical findings and detection of STIs in girls with suspected child
      sexual abuse were analyzed. RESULTS: One thousand thirty-four patients were
      included. Their median age was 7.9 years old. Anogenital findings were classified
      as class I (normal):38.4%, class II (nonspecific):38.1%, class III
      (specific):19.9% and class IV (definitive):3.6%. STIs were observed in 42
      patients (4.1%). A relation was established between STIs and the classification
      of physical findings: 10 (class II: 9; class III: 1) Neisseria gonorrhoeae, 17
      (class I: 2; class II: 8; class III: 7) Chlamydia trachomatis, 15 (class I: 2;
      class II: 10; class III: 3) Trichomonas vaginalis. Statistically significant
      differences for Trichomonas vaginalis (p= 0.01) and Neisseria gonorrhoeae (p <
      0.0001) were observed, with predominance of nonspecific clinical signs. Both
      nonspecific and specific findings were similarly observed for Chlamydia
      trachomatis (p= 0.03). CONCLUSIONS: Most cases of girls with suspected child
      sexual abuse had normal or nonspecific anogenital findings. The prevalence of
      STIs in these girls is low. Trichomonas vaginalis and Neisseria gonorrhoeae were
      related to nonspecific findings, while both nonspecific and specific findings
      were observed for Chlamydia trachomatis.

PMID- 26294143
TI  - Efficacy and safety of a decision rule for using antibiotics in children with
      pneumonia and vaccinated against pneumococcus. A randomized controlled trial.
AB  - INTRODUCTION: Although most cases of pneumonia in children younger than 5 years
      old have a viral nature, in everyday practice, they are frequently treated with
      antibiotics. A clinical decision rule (BPS:Bacterial Pneumonia Score) proved to
      be effective for identifying which children with pneumonia required antibiotics,
      but its performance has not been assessed in the population vaccinated against
      pneumococcal disease. Our objective was to assess whether using the BPS would
      allow to reduce antibiotic use compared to routine management of children with
      community acquired pneumonia vaccinated against pneumococcal disease. MATERIAL
      AND METHODS: Randomized, controlled, partially-blinded clinical trial with
      parallel groups comparing two approaches in the management of children aged 3-60
      months old in an outpatient setting because of pneumonia, who had been vaccinated
      with the pneumococcal conjugate vaccine.The BPS group received antibiotics with a
      BPS >4 points; while the control group was administered antibiotics at the
      discretion of the treating physician. The estimated sample size was calculated
      as, at least, 30 patients per group. The rate of antibiotic use and the clinical
      course were compared in both groups. RESULTS: Sixty-five patients (33 in the BPS
      group and 32 in the control group) were included; their average age was 17.5
      months old. Antibiotic use was significantly higher in the control group than in
      the BPS group (21/32 versus 9/33; OR: 5.09; 95% CI: 1.57-16.85; p= 0.001). Seven
      patients had an unfavorable course (three in the BPS group, and four in the
      control group). CONCLUSION: The use of the BPS allowed to reduce antibiotic use
      in the initial management of patients with pneumonia vaccinated against
      pneumococcal disease, without increasing the probability of an unfavorable course
      of the disease.

PMID- 26294144
TI  - Health-related quality of life in children with and without chronic conditions: A
      multicenter study.
AB  - INTRODUCTION: Chronic conditions (CCs) in the early stages of life may have an
      impact on various dimensions of health-related quality of life (HRQoL) in
      children. OBJECTIVE: To compare HRQoL in children with confirmed CCs, reported
      CCs, and without CC. POPULATION AND METHOD: Cross-sectional study conducted in
      2012 in the context of a larger research study carried out at schools in Cordoba
      and Bahia Blanca, and at Hospital Italiano of Buenos Aires and Hospital Prof. Dr.
      Juan P. Garrahan at Buenos Aires. The presence of a chronic condition was
      established by medical diagnosis at the hospital or as reported by
      schoolchildren's caregivers. Eight-to-twelve year-old children completed the
      KIDSCREEN-52 questionnaire on HRQoL, a pubertal development scale, and a family
      financial resource scale. The association between CCs and HRQoL adjusted by sex,
      age, pubertal development, maternal education level, and socioeconomic level was
      estimated. RESULTS: Six hundred and seventy children/ caregiver dyads
      participated; 13.3% (n= 89) had confirmed CCs, 14.5% (n= 97) were schoolchildren
      with reported CCs, and the rest corresponded to healthy schoolchildren. Their
      average age was 10.2 years old (standard deviation= 1.01); 54.8% were girls.
      Having a confirmed CC was associated with a higher frequency of low physical
      wellbeing (odds ratio |-OR-|: 2.61; 95% confidence interval |-95% CI-|:1.43
      4.76), while the presence of a reported CC was associated with a low score in
      psychological well-being (OR: 1.96; 95% CI: 1.06-3.63), self-perception (OR:
      2.22; 95% CI: 1.28-3.87), and parent relations (OR: 2.04; 95% CI: 1.21-3.44).
      CONCLUSIONS: Children with confirmed CCs showed a higher frequency of physical
      discomfort, and those with reported CCs showed discomfort in psychosocial areas
      compared to children without CCs.

PMID- 26294145
TI  - Parental perception of psychophysical health, nutritional status and oral health
      in relation to sociodemographic characteristics in children in Bariloche,
      Argentina: an epidemiological study.
AB  - INTRODUCTION: There is evidence of an association between social determinants and
      child health. OBJECTIVE: To identify sociodemographic characteristics related to
      child health inequalities and to analize the cumulative effect on health of risk
      factors based on these characteristics. POPULATION AND METHODS: We evaluated 4-13
      year-old children in Bariloche between June 2008 and May 2009. The following
      sociodemographic characteristics were taken into account: socioeconomic level,
      maternal education, adolescent pregnancy, medical coverage, unsafeness, and
      family habits. We assessed parental perception of physical, and social and
      emotional health, nutritional status and oral health in relation to these
      characteristics and the accumulation of risk factors. We used survey,
      anthropometry and oral examination. RESULTS: One hundred and eighty students
      participated. The level of maternal education was associated with the child's
      physical, social and emotional, and oral health. The percentage of children with
      missing teeth or cavities reached 77% among those whose mothers had, at most,
      completed primary school, compared to 13% among those whose mothers had completed
      tertiary school or university. The possibility of perceiving a non-optimal
      physical, and social and emotional health increased 1.8 and 1.4 times with each
      risk factor, respectively, and the possibility of having missing teeth or
      cavities was twice as much with each additional risk factor. Overweight and
      obesity was observed in 27.3% and 8.7% of students, respectively, and no
      relationship was found with sociodemographic characteristics. CONCLUSIONS: A low
      family socioeconomic level and a low maternal education level were associated
      with a higher prevalence of unfavorable health outcomes. Multiple risk factors
      have an cumulative effect on parental perception of physical, social and
      emotional, and oral health.

PMID- 26294146
TI  - Assessment of 200 pediatric patients exposed to rabies risk.
AB  - BACKGROUND/PURPOSE: Rabies is still an important health problem particularly in
      underdeveloped or developing countries. In this study, the aim was to investigate
      demographic characteristics and vaccination schedules of cases suspected of
      having rabies and admitted to the Pediatric Emergency Clinic of our hospital,
      which serves as one of the Rabies Vaccination Centers in our province. METHODS:
      In our study, medical records of 200 patients admitted to the Pediatric Emergency
      Clinic with suspicion of risk of contact with the rabies virus were
      retrospectively analyzed. RESULTS: Of those 200 cases, rabies risk was found to
      be greater in the 5-9 year old group. There was a history of having been bitten
      by dogs in 68.5% of cases, cat scratch in 29.5%, and contact with other animals
      in 2%. While 76% of animals were stray animals, only 11% of them had an owner and
      had been vaccinated, and were under supervision. Rabies vaccination only had been
      administered to 42.5% of admitted patients, tetanus and rabies vaccination to
      51.5%, tetanus; rabies vaccination and human rabies immune globulin were
      administered to 6%. Post-exposure prophylaxis was found to have been given as
      recommended to 83.5% of cases. CONCLUSION: Rabies remains an important public
      health problem in developing countries Like ours. We consider that public
      awareness should be raised; local authorities should devote efforts to control
      stray animals and supervise such services, and updated guidance and training
      should be provided to the concerned health staff to reduce the risk of rabies.

PMID- 26294148
TI  - Impact of the time of diagnosis on the postoperative outcome of newborn infants
      with congenital heart disease in a public hospital in Argentina.
AB  - Congenital heart diseases account for 13% of child mortality, and late diagnosis
      increases morbidity and mortality. The objective of this study was to assess the
      impact of the time of diagnosis in newborn infants on the postoperative course.
      The time of diagnosis was classified into prenatal, before or after discharge
      from the maternity center. Two hundred ninety-nine patients were included; their
      gestational age was 38 +/- 2.6 weeks and their birth weight was 3.22 +/- 0.6 kg.
      Two hundred sixty-six patients underwent surgery, 13 were excluded due to the
      characteristics of the lesion, and 10 because of hemodynamic collapse, while 10
      were treated at the Cath Lab or were operated beyond the neonatal period. Only 19
      patients (7%) were diagnosed before birth; most were patients who had health
      insurance, lived in the City of Buenos Aires or in capital cities of other
      provinces. The time of diagnosis was not associated with differences in
      mortality; however, an association was observed with a poor preoperative clinical
      status, with 3.6% of patients who died before surgery. Postoperative survival was
      89.5%; overall survival was 83%. 

PMID- 26294149
TI  - Implementation in Buenos Aires City of a program to prevent neurological damage
      caused by hypoxic-ischemic encephalopathy: Therapeutic hypothermia.
AB  - Therapeutic hypothermia is the standard of care for hypoxic-ischemic
      encephalopathy (HIE). This treatment was implemented at a regional level by the
      perinatal network of the City of Buenos Aires. The following are the objectives
      of this article: 1. To describe the implementation of the network's hypothermia
      treatment program; 2. To report treatment-associated complications, adverse
      events and mortality. The program was implemented in stages: 1) 2009-2010.
      Training and instruction on how to use the equipment. 2) 20102014. Treatment and
      follow-up of patients with moderate or severe HIE. Up to October 2014, 27 newborn
      infants received hypothermia treatment with moderate (n= 15) and severe (n= 12)
      HIE. None of the patients died during treatment. Three newborn infants were lost
      to follow-up. Among the 16 survivors older than one year old, three have severe
      neurological disability. Program implementation was plausible. It is imperative
      to train health care providers on how to identify patients with HIE. 

PMID- 26294150
TI  - Refusal to have children vaccinated: A challenge to face.
AB  - Vaccinations are a critical public health tool. However, a significant number of
      people decide not to get vaccinated or refuse to have their children immunized.
      Physicians who recommend people who have an indication for vaccination not to get
      vaccinated go against official immunization programs, contradict sound scientific
      evidence, and put themselves at medical/legal risks because of their
      prescriptions. Parents who decide not to have their children vaccinated make this
      decision based on ideological or religious beliefs, or because of fads or
      snobbism, among other reasons, and this behavior affects their children's
      epidemiological protection and makes them prone to getting the disease. Health
      effects of this kind are harmful for both those children and the community.
      Education and the adequate dissemination among the population, epidemiological
      and adverse event surveillance, a clear legal frame stating responsibilities,
      rights and obligations, and an informed consent for non vaccination, among other
      things, are tools that may help to eradicate such behavior. The best way to
      prevent vaccine-related adverse events is to eradicate disease so that
      vaccination is no longer necessary.

PMID- 26294147
TI  - Characteristics of pediatric intensive care residency programs in Argentina: A
      national survey.
AB  - INTRODUCTION: Pediatric intensive care residency programs have been in place in
      Argentina for just a few years. Knowing their status offers the possibility to
      establish strategies to help with professional development and training.
      OBJECTIVES: 1) To describe the characteristics of pediatric intensive care
      residency programs across Argentina. 2) To assess whether certain characteristics
      are related to a higher vacancy filling rate. 3) To assess job placement in the
      hospital where residents are trained. DESIGN: Descriptive, observational study.
      National survey. INCLUSION CRITERIA: Pediatric intensive care residency programs
      in place between April 1st, 2014 and May 31st, 2014. RESULTS: Thirty-one
      residency programs were analyzed. Only 11/31 had an annual hospitalization volume
      >400 patients. There were no guidelines and/or criteria for care in 9/31. The
      program suited the national reference framework in 17/31. There was no head of
      residents or resident trainer in 13/31. Only 5/31 had been certified by the
      Ministry of Health. There were 65 vacancies; this number increased in the past
      four years; vacancy filling rate decreased from 59% in 2009 to 30% in 2013. Sixty
      percent of residents got a job in the pediatric intensive care unit where they
      were trained. A multivariate logistic regression analysis identified the outcome
      measure annual hospitalization volume >400 patients as an independent predictor
      of vacancy filling rate >60%. CONCLUSIONS: 1) Vacancy filling is deficient. 2)
      The number of certified residency programs is scarce. 3) Pediatric intensive care
      units with a higher number of hospitalizations were associated with a higher
      vacancy filling rate. 4) More than half of residents got a job in the pediatric
      intensive care unit where they were trained.

PMID- 26294151
TI  - Presumed perinatal ischemic stroke: A review.
AB  - The risk of stroke is actually highest during the perinatal period. However, some
      newborn infants may have no signs indicative of the need of brain imaging, or
      brain images taken may not be sensitive enough to diagnose ischemic injuries; so,
      the diagnosis of stroke may be delayed several months or years. The neurological
      picture in patients with perinatal stroke detected through neuroimaging months or
      years after the neonatal period is called presumed perinatal ischemic stroke.
      Although a presumed perinatal ischemic stroke is just a confirmation of the
      existence of an important level of underdiagnosis in relation to perinatal
      stroke, establishing the extent of this condition has allowed to improve
      knowledge on perinatal ischemic vascular disease. 

PMID- 26294152
TI  - [Update on leukoreduction therapies as alternatives for the treatment of severe
      pertussis].

PMID- 26294153
TI  - [Patient safety: Glossary].
AB  - Patient safety and quality of care has become a challenge for health systems.
      Health care is an increasingly complex and risky activity, as it represents a
      combination of human, technological and organizational processes. It is
      necessary, therefore, to take effective actions to reduce the adverse events and
      mitigate its impact. This glossary is a local adaptation of key terms and
      concepts from the international bibliographic sources. The aim is providing a
      common language for assessing patient safety processes and compare them. 

PMID- 26294154
TI  - [Bioethics colection: A new contribution in Archivos].

PMID- 26294156
TI  - [Bazex-Dupre-Christol syndrome: Case series].
AB  - Bazex-Dupre-Christol syndrome is an X-linked dominantly inherited disorder
      characterized by congenital hypotrichosis, hypohidrosis, follicular atrophoderma,
      multiple milia and basal cell carcinomas. We present a girl and her family with
      this syndrome. Our patient, her 5 month old brother and her 17 year old brother
      had multiple milia and scalp and eyebrows hypotrichosis. Her 8 year old brother
      had multiple milia and follicular atrophoderma. Her mother had hypohidrosis and
      congenital scalp and eyebrows hypotrichosis, as well as a right paranasal lesion
      suggestive of basal cell carcinoma. We emphasize the importance of precise
      diagnosis and clinical follow up of these patients due to the possibility of
      developing basal cell carcinomas. 

PMID- 26294157
TI  - [Clinical and epidemiological characteristics of ocular trauma in children under
      14 years of age].
AB  - Pediatric ocular trauma is common and the leading cause of non congenital
      unilateral blindness. The information in developing countries is scarce. The
      objective of this case series is to describe clinical and epidemiological
      characteristics of ocular trauma in children under 14 years of age who visited
      Hospital Dr. Rodolfo Robles Valverde in Guatemala City in 2010. In this study 119
      patients were included. School-aged (7-9 years) male gender was the most
      affected. Closed globe injury was the commonest. The most frequent objects
      causing the lesions were: wooden objects, toys and chemicals. Trauma occurred
      most frequently at home. Twenty one of the patients were surgically intervened.
      Education and prevention programs for pediatric ocular trauma are necessary. 

PMID- 26294158
TI  - [Hyaline fibromatosis syndrome: case report of two siblings].
AB  - Hyaline fibromatosis syndrome is a rare autosomal recessive disease characterized
      by the presence of contracture and joint pain, hyperpigmented plaques and nodules
      and gingival hypertrophy. These findings are the result of the accumulation of a
      hyaline amorphous material similar to collagen type VI in different tissues. This
      syndrome includes systemic hyalinosis and juvenile hyaline fibromatosis, two
      entities that for years were considered separately. However, it has been
      documented that the cause of both entities is located in the same gene and the
      clinical features and age of presentation are overlapped. In this study two cases
      of sisters from a same colombian family affected by the disease are presented. 

PMID- 26294160
TI  - [Posterior reversible encephalopathy in a girl with systemic lupus erythematosus:
      Report of a case].
AB  - Posterior reversible encephalopathy is a rare disease in children. Clinical
      manifestations include headache, seizures, visual disturbances and altered
      consciousness associated with typical magnetic resonance images of the nervous
      system. The syndrome usually manifests in patients with eclampsia, solid organ
      transplantation, haematologic, renal and autoimmune diseases among other less
      common causes and it is often triggered after a hypertensive crisis or use of
      immunosuppressive drugs. Less common pathogenic factors as blood transfusion, use
      of immunoglobulins or an underlying infection can be associated. In this case a
      girl with systemic lupus erythematosus and exposed to multiple etiopathogenic
      factors developed posterior reversible encephalopathy. 

PMID- 26294159
TI  - [Cerebellar cognitive affective syndrome].
AB  - INTRODUCTION: The diagnosis of Cerebellar Cognitive Affective Syndrome should be
      considered in patients with cerebellar lesions who also suffer cognitive deficits
      associated with visuospatial or executive neuropsychological disorders,
      expressive language disorders and affective disorders. CLINICAL CASE: A 16 year
      old adolescent diagnosed with Attention Deficit Hyperactivity Disorder at the age
      of 7 presents with emotional instability, apathy, and speech and reading
      difficulties. Neuropsychological tests show visuospatial difficulties. A brain
      magnetic resonance imaging is performed due to impaired coordination and fine
      motor movements and shows atrophy of the cerebellar vermis. The clinical picture
      suggests a diagnosis of Cerebellar Cognitive Affective Syndrome. The cerebellum
      is mostly known for its motor role. However, it is also involved in higher
      cognitive functions, expression of emotion and behavioral regulation. Cerebellar
      Cognitive Affective Syndrome is a relatively unknown diagnosis and should be
      included in the differential diagnosis of neuropsychiatric disorders with
      cerebellar lesion.

PMID- 26294161
TI  - [Occult arterial hypertension after repaired aortic coarctation].
AB  - Coarctation of the aorta, repaired in childhood, is a congenital heart disease
      frequently seen in adulthood. In these patients there is a higher incidence of
      hypertension during daily activities and exercise despite a correct surgical
      repair. Since hypertension may only be seen by ambulatory blood pressure
      monitoring (occult arterial hypertension) we should also look for indirect signs,
      such as the development of left ventricular hypertrophy.

PMID- 26294162
TI  - [Linear immunoglobulin A bullous dermatosis: Two cases report].
AB  - Linear immunoglobulin A bullous dermatosis is a rare entity with frequent
      spontaneous resolution. It usually presents in children with average age of 4.5
      years. Its incidence is about 0.5-2.3 cases/million individuals/year. It is,
      after dermatitis herpetiformis, the most frequent paediatric blister disorder. It
      usually appears in bouts with acute development of vesicles in strings of pearls;
      affecting the perioral area and genitalia. Diagnosis is based on the clinical
      signs and symptoms and biopsy of the skin with subepidermal blister and a linear
      band of immunoglobulin A in the direct immunofluorescence. Often, diagnosis is
      made late because of the unawareness of this disease. 

PMID- 26294163
TI  - Rupture and displacement of umbilical arterial catheter: Bilateral arterial
      occlusion in a very low birth weight preterm.
AB  - Umbilical vessel catheterization is a common procedure in Neonatal Intensive Care
      Units, especially in very low birthweight infants. Rarely, umbilical artery
      catheters break, and the retained fragments can cause thrombosis, infection,
      distal embolization, and even death. Herein, we describe a neonate with
      clinically significant bilateral limb ischemia developing after removal of a
      broken umbilical artery catheter. He was under vasodilator treatment in addition
      to fibrinolytic and anticoagulants. The evolution was favourable. 

PMID- 26294164
TI  - [Intussusception in infant with diagnostic botulism: A case report].
AB  - Botulism is an important public health problem in Argentina. It is a potentially
      fatal disease, and its diagnosis may be difficult. There are rare presentation
      forms of the disease, such as acute abdomen. We present a 4-month baby with a 3
      day constipation condition, associated with weakness and abnormal eating attitude
      in the last 12 hours. The baby presented preserved muscle tone, with no changes
      in sucking or deglutition according to the mother's observations. Altered
      sensorium and acute abdomen were found; the patient was entered into the
      operating room with presumptive diagnosis of intussusception, which was confirmed
      by pneumatic desinvagination. During hospitalization, the patient did not make
      good progress and presented weak cry, progressive hypotonia and respiratory
      failure requiring intensive care. Clostridium botulinum was isolated from the
      stool sample and botulinum toxin type A was isolated from serum. The patient was
      treated with equine botulinum toxin. Twenty five days after admission, he was
      totally recovered.

PMID- 26294165
TI  - [Polydactyly, holoprosencephaly, cleft lip and cleft palate are not always what
      they seem: Case report].
AB  - We report a male infant with midline defects, congenital heart disease and
      polydactyly, features suggestive of trisomy 13. However, the report of the
      karyotype was normal. By clinical findings the final diagnosis was likely to be
      Pseudotrisomy 13. Although the prognosis is poor in both conditions, the genetic
      study is always necessary to establish an adequate genetic counseling. Although
      there are syndromes with similar presentation as Meckel syndrome, Smith-Lemli
      Opitz syndrome, Pallister-Hall syndrome and hydrolethalus, it is possible to make
      a diagnostic approach based on the perinatal history, birth weight, survival
      time, and some characteristics of each syndrome. However, limitations may exist
      to perform genetic studies in some countries, therefore the clinical criteria may
      be relevant.

PMID- 26294166
TI  - [Beta thalassemia intermedia: clinical characteristics and molecular analysis.
      Case series].
AB  - Beta thalassemia intermedia is a quantitative haemoglobinopathy covering a broad
      clinical spectrum, that results from the presence of one or two HBB gene
      mutations associated with secondary and/or tertiary genetic modifiers. We analyze
      the clinical and laboratory features of 29 patients with beta thalassemia
      intermedia, assessed over a period of 23 years. Median age was 10.8 years (range:
      0.34-60.4). Hypochromic microcytic anemia was seen in 100% of the patients, while
      only 17.2% had splenomegaly and occasional transfusion requirement. The molecular
      analysis of patients detected: 3 with two HBB affected genes; 2 with one HBB
      affected gene and alpha quadruplicate/triplicate genes; 23 with one HBB affected
      gene and alpha triplicate genes and 1 with two HBB affected genes and
      polymorphisms of gamma genes. The adequate identification of these patients
      enables us to give appropriate genetic counseling and implementation of regular
      clinical follow up.

PMID- 26294167
TI  - [Acheiropodia: first case report in Argentina].
AB  - Acheiropodia is a very rare disease with autosomal recessive inheritance
      characterized by limb reduction defects. It has been described mainly in Brazil.
      The aim of this report is to describe the first reported cases in Argentina in
      two affected twins. Patients were reported to the National Registry of Congenital
      Anomalies of Argentina (RENAC). Both twins had limb reduction defect including
      hands, forearms, feet and fibulae. These patients are the first reported cases of
      acheiropodia syndrome in Argentina. Immigration from Brazil could explain this
      case in our population. 

PMID- 26294168
TI  - Anti-cancer activity of trans-chalcone in osteosarcoma: Involvement of Sp1 and
      p53.
AB  - Osteosarcoma is the most common bone cancer. Although the emergence of multidrug
      therapies has improved available treatments for osteosarcoma, approximately 30%
      of patients will still develop metastasis. Currently, much anticancer therapy
      uses drugs that affect oncogenes/tumor suppressor genes, such as p53 (up
      regulation) and Sp1 (down-regulation). Chalcones are secondary metabolites of
      plants and have been demonstrated to induce apoptosis in human cancer cells.
      Building on this knowledge, we evaluated the ability of trans-chalcone to reduce
      viability, to induce apoptosis, and to alter gene expression of p53 and Sp1 in
      human osteosarcoma cell lines. We found that treatment of trans-chalcone
      inhibited growth of osteosarcoma cells in a dose- and time-dependent manner, with
      significant inhibition at 10 MUM after 48 h; apoptosis was also induced in a dose
      dependent manner, with 1.9- and 3.6-fold induction at 10 MUM and 50 MUM,
      respectively, compared to non-treated cells. Further experiments suggest that
      trans-chalcone affected Sp1 down-regulation at the transcriptional level, whereas
      trans-chalcone up-regulated p53 expression at the post-translational level. trans
      chalcone and its derivatives could be important in the development of future
      clinical trials in osteosarcoma. (c) 2015 Wiley Periodicals, Inc.

PMID- 26294169
TI  - The impact of Advanced Life Support in Obstetrics (ALSO) training in low-resource
      countries.
AB  - OBJECTIVE: To examine the effects of the Advanced Life Support in Obstetrics
      (ALSO) program on maternal outcomes in four low-income countries. METHODS: Data
      were obtained from single-center, longitudinal cohort studies in Colombia,
      Guatemala, and Honduras, and from an uncontrolled prospective trial in Tanzania.
      RESULTS: In Colombia, maternal morbidity and the number of near misses increased
      after ALSO training, but maternal mortality decreased. In Guatemala, sustained
      reductions in overall maternal mortality and mortality from postpartum hemorrhage
      (PPH) were recorded after ALSO implementation. In Honduras, there was a
      significant decrease in episiotomy rates, and increases in active management of
      the third stage of labor (AMTSL), vacuum-assisted delivery, and reported comfort
      managing obstetric emergencies. In Tanzania, the frequency of PPH and severe PPH
      decreased after training, while management improved. CONCLUSION: In low-income
      countries, ALSO training was associated with decreased in-hospital maternal
      mortality, episiotomy use, and PPH. AMTSL and vacuum-assisted vaginal delivery
      increased in frequency after ALSO training.

PMID- 26294170
TI  - Robotic nerve-sparing radical hysterectomy for locally advanced cervical cancer
      after neoadjuvant chemotherapy.
AB  - OBJECTIVE: To evaluate the feasibility and safety of robotic nerve-sparing
      radical hysterectomy for locally advanced cervical cancer (LACC). METHODS: In a
      retrospective study, data were analyzed for patients treated for cervical cancer
      at a center in Beijing, China, between December 2011 and September 2013. Patients
      were subdivided into those with early-stage disease (FIGO stage IA2-IB1) who were
      treated by robotic surgery (group 1), and those with LACC (stage IB2-IIB) who
      were treated by robotic surgery after neoadjuvant chemotherapy (NACT; group 2).
      Therapeutic outcomes and complications were compared. RESULTS: Group 1 included
      32 patients and group 2 included 22 patients. Two patients in group 2 did not
      respond to NACT and did not undergo surgery. The operative outcomes and
      incidences of complications did not differ significantly between the two groups
      (P>0.05 for all). There were no differences in nodal yield, lengths of
      parametrium removed, or vaginal cuff length (P>0.05 for all). During a mean
      follow-up of 26months, no patient experienced recurrence. CONCLUSION: Robotic
      nerve-sparing radical hysterectomy was found to be feasible and safe for LACC
      after NACT. A larger case series with longer follow-up data is needed to justify
      its widespread application.

PMID- 26294171
TI  - Probability of cesarean delivery after successful external cephalic version.
AB  - OBJECTIVE: To identify factors associated with cesarean delivery following
      successful external cephalic version (ECV). METHODS: In a prospective study, data
      were obtained for ECV procedures performed at Cruces University Hospital, Spain,
      between March 2002 and June 2012. Women with a singleton pregnancy who had a
      successful, uncomplicated ECV and whose delivery was assisted at the study
      hospital, with the fetus in cephalic presentation, were included. A multivariate
      model of risk factors of cesarean delivery was developed. RESULTS: Among 627
      women included, 92 (14.7%) delivered by cesarean. A cesarean was performed among
      33 (8.5%) of 387 women with spontaneous labor versus 59 (24.6%) of 240 who were
      induced (P < 0.001). Multivariate analysis showed that higher BMI (P = 0.006),
      labor induction (P = 0.001), and prior cesarean (P < 0.001) were associated with
      cesarean. Time between ECV and delivery was inversely associated with probability
      of cesarean during the first 2 weeks. Thus, the probabilities of cesarean
      delivery on the first day were 0.53 (95% CI 0.35-0.71) and 0.34 (95% CI 0.18
      0.51) following induced and spontaneous labor, respectively. On the seventh day,
      the probabilities were 0.23 (95% CI 0.15-0.32) and 0.12 (95% CI 0.07-0.18),
      respectively. CONCLUSION: Following ECV, induction of labor, an interval of less
      than 2 weeks to delivery, BMI, and previous cesarean were associated with an
      increased risk of cesarean.

PMID- 26294172
TI  - Pharmacokinetics and Tolerability of Rufinamide Following Single and Multiple
      Oral Doses and Effect of Food on Pharmacokinetics in Healthy Chinese Subjects.
AB  - BACKGROUND: Rufinamide is a triazole derivative that is structurally unrelated to
      currently marketed antiepileptic medications for add-on treatment of seizures in
      the setting of Lennox-Gastaut syndrome in patients from the age of 4 years.
      OBJECTIVE: The purpose of this study was to determine the pharmacokinetic and
      safety profile of single and multiple doses of rufinamide in healthy Chinese
      subjects. The effects of food and gender on the pharmacokinetic properties of
      rufinamide were also evaluated. METHODS: In the single-dose study, volunteers
      were randomly assigned to 4 dose groups and received a single dose of 200, 400,
      800, 1200 mg rufinamide tablets under fasting condition. Ten subjects in the 200
      mg dose group were randomly assigned to either a high-fat or non-high-fat
      breakfast group in each study period. The drug administration was separated by a
      washout period of 7 calendar days. In the multiple-dose study, 10 subjects were
      administered on an empty stomach rufinamide 200 mg twice daily for 6 consecutive
      days. Liquid chromatography tandem mass spectrometry (LC-MS/MS) method was
      applied to determine plasma concentration of rufinamide. Pharmacokinetic
      parameters, including the maximum plasma concentration (C max), the time to peak
      concentration (t max), the area under the plasma concentration versus time curve
      from time 0 to the last measurable concentration (AUC0-t ) and from time 0 to
      infinity (AUC0-infinity), terminal elimination half-life (t 1/2), apparent volume
      of distribution (V d), apparent clearance (CL), average residence time (MRT),
      area under the plasma concentration versus time curve from time 0 to the last
      measurable concentration at steady state (AUCss), peak concentration (C max,ss)
      and trough level concentration (C min,ss) at steady state were calculated using
      non-compartmental models. Tolerability was assessed based on investigator
      inquiries, spontaneous reports and clinical evaluations. RESULTS: Rufinamide
      displayed a dose-dependent, but sub-proportional increase in exposure following
      single-dose and repeated dose administration. After administration of single dose
      of 200, 400, 800 and 1200 mg, without food, the rufinamide mean C max (standard
      deviation, SD) was 1806.5 (526.4), 2490 (564.8), 3719 (976.1) and 4166 (1187.1)
      MUg/L, respectively. Mean AUC0-t (SD) was 34,571 (9484), 56,246 (18,077), 89,022
      (23,379) and 107,316 (34,766) MUg.h/L, respectively. While in fed condition at
      the dosage of 200 mg, mean C max (SD) and mean AUC0-t (SD) were 2363 (582) MUg/L
      and 40,593 (10,516) MUg.h/L, respectively. After administration of multiple
      doses, arithmetic mean (SD) values of C max and AUC0-t were 3566 (873) MUg/L and
      62,803 (19,873) MUg.h/L, respectively. The steady state was achieved by day 3 of
      multiple dosing after 2 daily doses (twice a day), the corresponding accumulation
      factor (AUCss/AUC0-t) was 0.9057. Although there were no substantial effects on
      exposure resulting from gender differences, a notable food effect was observed,
      with AUC and C max increased by 17.4 and 30.8 %, respectively. Single- and
      multiple-dose phases were generally safe and well tolerated. CONCLUSION: Overall,
      15 % (6/40) of subjects experienced a mild indisposition with no serious adverse
      events. On single and multiple dosing, rufinamide exhibited nonlinear
      pharmacokinetics and was well tolerated in healthy Chinese subjects.

PMID- 26294173
TI  - The intestinal epithelium as guardian of gut barrier integrity.
AB  - A single layer of epithelial cells separates the intestinal lumen from the
      underlying sterile tissue. It is exposed to a multitude of nutrients and a large
      number of commensal bacteria. Although the presence of commensal bacteria
      significantly contributes to nutrient digestion, vitamin synthesis and tissue
      maturation, their high number represents a permanent challenge to the integrity
      of the epithelial surface keeping the local immune system constantly on alert. In
      addition, the intestinal mucosa is challenged by a variety of enteropathogenic
      microorganisms. In both circumstances, the epithelium actively contributes to
      maintaining host-microbial homeostasis and antimicrobial host defence. It deploys
      a variety of mechanisms to restrict the presence of commensal bacteria to the
      intestinal lumen and to prevent translocation of commensal and pathogenic
      microorganisms to the underlying tissue. Enteropathogenic microorganisms in turn
      have learnt to evade the host's immune system and circumvent the antimicrobial
      host response. In the present article, we review recent advances that illustrate
      the intense and intimate host-microbial interaction at the epithelial level and
      improve our understanding of the mechanisms that maintain the integrity of the
      intestinal epithelial barrier. 

PMID- 26294174
TI  - The ethics of killing human/great-ape chimeras for their organs: a reply to Shaw
      et al.
AB  - The aim of this paper is to critically examine David Shaw, Wybo Dondorp, and
      Guido de Wert's arguments in favour of the procurement of human organs from
      human/nonhuman-primate chimeras, specifically from great-ape/human chimeras. My
      main claim is that their arguments fail and are in need of substantial revision.
      To prove this I first introduce the topic, and then reconstruct Shaw et al.'s
      position and arguments. Next, I show that Shaw et al.: (1) failed to properly
      apply the subsidiarity and proportionality principles; (2) neglected species
      overlapping cases in their ethical assessment; (3) ignored the ethics literature
      on borderline persons; and (4) misunderstood McMahan's two-tiered moral theory.
      These mistakes render an important part of their conclusions either false or
      problematic to the point that they would no longer endorse them. Finally I will
      briefly mention a possible multipolar solution to the human organ shortage
      problem that would reduce the need for chimeras' organs. 

PMID- 26294175
TI  - The Oxidation of Pyrrole.
AB  - The dearomatization of heterocycles has been a powerful means for producing
      functional molecules in synthesis. In the case of pyrroles, reductive methods
      (such as the Birch reduction) have been most widely exploited, while oxidative
      methods are generally dismissed as too difficult or unpredictable to be useful.
      However, since the early twentieth century considerable research has been carried
      out on the controlled oxidation of pyrroles to give highly functionalized
      products, using a variety of oxidants. This review presents a summary of all work
      up until the present day in the area of pyrrole oxidation, looking at the use of
      peroxide, singlet oxygen, hypervalent iodine reagents, a range or organic and
      inorganic oxidants, and electrochemical approaches. It also offers some
      perspective on the potential future role of pyrrole oxidation in synthesis. 

PMID- 26294176
TI  - Dynamics of H Atom Production from Photodissociation of Acetic Acid-d(1).
AB  - Detailed dissociation dynamics of H(D) from acetic acid-d1 (CH3COOD) has been
      investigated upon electronic excitation to the (1)(n,pi*), S1 state at 205 nm by
      measuring laser-induced fluorescence spectra of the fragment H(D) atoms. In
      addition, quantum yields for the H(D) atom dissociation channels, CH3COO + D and
      CH2COOD + H, were measured, which are 0.07 +/- 0.03 and 0.17 +/- 0.03,
      respectively. From the Doppler broadened spectra, the center-of-mass
      translational energy releases into products were obtained. To determine the
      detailed dissociation dynamics, two-dimensional potential energy surfaces along
      the reaction coordinate including the coordinate directly coupled to the
      dissociation coordinate were examined by employing quantum chemical calculations.
      For the CH3COO + D channel, the coupled coordinate is the dihedral angle of D
      against the COO plane. The dissociation of D(H) from acetic acid should take
      place along the triplet surface via surface crossing from the initially excited
      S1 state. Along the triplet surface, an exit channel barrier exists, which
      originates from the structural difference between the T1 and the product
      asymptotes, especially the dihedral angle of D against the COO plane. The
      observed translational energy releases were successfully estimated by the barrier
      impulsive model based upon the calculated two-dimensional potential energy
      surfaces at the B3LYP/cc-pVDZ level of theory. 

PMID- 26294177
TI  - Diplonemids.
AB  - Lukes et al. introduce an enigmatic group of unicellular eukaryotes called the
      diplonemids, which according to recent surveys may be widespread in marine
      ecosystems. 

PMID- 26294178
TI  - North American velvet ants form one of the world's largest known Mullerian
      mimicry complexes.
AB  - Color mimicry is often celebrated as one of the most straightforward examples of
      evolution by natural selection, as striking morphological similarity between
      species evolves in response to a shared predation pressure. Recently, a large
      North American mimetic complex was described that included 65 species of
      Dasymutilla velvet ants (Hymenoptera: Mutillidae). Beyond those 65 species,
      little is known about how many species participate in this unique Mullerian
      complex, though several other arthropods are thought to be involved as Mullerian
      mimics (spider wasps) and Batesian mimics (beetles, antlions, and spiders; see
      references in). Mullerian mimicry is similarity in appearance or phenotype among
      harmful species, while Batesian mimicry is similarity in which not all species
      are harmful. Here, we investigate the extent of the velvet ant mimicry complex
      beyond Dasymutilla by examining distributional and color pattern similarities in
      all of the 21 North American diurnal velvet ant genera, including 302 of the 361
      named species (nearly 84%), as well as 16 polymorphic color forms and an
      additional 33 undescribed species. Of the 351 species and color forms that were
      analyzed (including undescribed species), 336 exhibit some morphological
      similarities and we hypothesize that they form eight distinct mimicry rings
      (Figure 1A; Supplemental Information). Two of these eight mimicry rings, red
      headed Timulla and black-headed Timulla, were not documented in earlier
      assessments of mimicry in velvet ants, and are newly described here. These
      findings identify one of the largest known Mullerian mimicry systems worldwide
      and provide a novel system to test hypotheses about aposematism and mimicry,
      especially those regarding the evolution of imperfect mimicry.

PMID- 26294179
TI  - Whistled Turkish alters language asymmetries.
AB  - Whistled languages represent an experiment of nature to test the widely accepted
      view that language comprehension is to some extent governed by the left
      hemisphere in a rather input-invariant manner. Indeed, left-hemisphere
      superiority has been reported for atonal and tonal languages, click consonants,
      writing and sign languages. The right hemisphere is specialized to encode
      acoustic properties like spectral cues, pitch, and melodic lines and plays a role
      for prosodic communicative cues. Would left hemisphere language superiority
      change when subjects had to encode a language that is constituted by acoustic
      properties for which the right hemisphere is specialized? Whistled Turkish uses
      the full lexical and syntactic information of vocal Turkish, and transforms this
      into whistles to transport complex conversations with constrained whistled
      articulations over long distances. We tested the comprehension of vocally vs.
      whistled identical lexical information in native whistle-speaking people of
      mountainous Northeast Turkey. We discovered that whistled language comprehension
      relies on symmetric hemispheric contributions, associated with a decrease of left
      and a relative increase of right hemispheric encoding mechanisms. Our results
      demonstrate that a language that places high demands on right-hemisphere typical
      acoustical encoding creates a radical change in language asymmetries. Thus,
      language asymmetry patterns are in an important way shaped by the physical
      properties of the lexical input.

PMID- 26294180
TI  - Is the expression of sense and antisense transgenes really sufficient for
      artificial piRNA production?
AB  - Animals have evolved an elegant defense system against a diverse range of selfish
      elements such as transposons. In animal germ line cells, PIWI proteins and small
      RNAs associated with PIWI proteins (piRNAs) are at the heart of this defense
      system. piRNAs are 23-30-nt-long small RNAs that act as sequence-specific guides
      for PIWI proteins. PIWI proteins possess a slicer activity that is guided by
      piRNAs; the PIWI-piRNA complex thus silences transposon activity by cleaving
      transposon RNAs. At present, how de novo piRNA production occurs against a new
      non-self element is largely unknown. A recent study by Itou et al. using reporter
      transgenic mice concluded that the concomitant expression of sense and antisense
      RNA transcripts is sufficient for piRNA production. Our bioinformatic analysis
      using the same piRNA datasets, however, demonstrates that the introduction of the
      antisense reporter construct alone produces transgene-derived piRNAs, which is
      inconsistent with a part of the conclusions of Itou et al.

PMID- 26294181
TI  - Reply to Shoji and Katsuma.
AB  - Our paper reports a novel strategy for the artificial introduction of DNA
      methylation in mouse gonocytes. The manuscript presents data showing that the
      concomitant expression of sense and anti-sense of EGFP transgenes in embryonic
      male germ cells induces gene silencing via the piRNA pathway and that the
      expression of an antisense Dnmt3L transgene induces silencing of the endogenous
      Dnmt3L gene.

PMID- 26294182
TI  - Neural Circuits: From Structure to Function and Back.
AB  - The new field of connectomics aims to obtain fine-grained anatomical connectivity
      data for vertebrate brains. A recent study highlights the types of experiments
      that will be necessary in order to draw conclusions about function from
      anatomical connectivity. 

PMID- 26294183
TI  - Vision Science: Can Rhodopsin Cure Blindness?
AB  - Outer retinal degeneration is the leading cause of blindness in the developed
      world. A new study now demonstrates that ectopic expression of human rhodopsin in
      the inner retina, mediated by viral gene therapy, can restore light sensitivity
      and some vision to mice blind from outer retinal degeneration. 

PMID- 26294184
TI  - Physiology: Female Flies Have the Guts for Reproduction.
AB  - Females of many species adjust their diet to support the energetic requirements
      of egg production. New research shows how, in flies, females remodel their gut
      and modify gut physiology too. 

PMID- 26294185
TI  - Category Learning: Top-Down Effects Are Not Unique to Humans.
AB  - Human infants use top-down information to learn the sound category of their
      language. A new study using an artificial language containing species-specific
      vocalizations shows that songbirds may rely on a similar mechanism. 

PMID- 26294186
TI  - Invertebrate Neurobiology: Bridging the Gap with a Local Command Interneuron.
AB  - A recent study has identified a command interneuron that controls the motor
      sequence for searching behavior in stick insect. The findings have implications
      for context-dependent behavioral selection. 

PMID- 26294187
TI  - Cytokinetic Abscission: Timing the Separation.
AB  - New work identifies components of the abscission checkpoint that prevent
      premature severing of the bridge connecting cells at the end of cell division.
      Kinase activities allow the membrane remodeling machinery to take their mark, but
      prevent them from leaving the starting block. 

PMID- 26294188
TI  - Plant Architecture: The Long and the Short of Branching in Potato.
AB  - A new report details the interaction between two isoforms of an important
      BRANCHED1 (BRC1) transcription factor gene in potato. The regular long form
      inhibits lateral branching, like BRC1 in other species, but a modified protein
      that originates from alternative BRC1 splicing inhibits the long form and
      promotes lateral branching. 

PMID- 26294189
TI  - Evolution: Anti-speciation in Walking Sticks.
AB  - The interplay between selection and genetic exchange at a color locus between
      populations of Timema walking sticks acts as an anti-speciation phenotype. This
      actively counteracts speciation and offers a general mechanism to explain the
      porous nature of species boundaries. 

PMID- 26294190
TI  - Neurodegeneration: A Leg Up on TDP-43.
AB  - TDP-43 is a key disease protein for amyotrophic lateral sclerosis but how it
      drives motor neuron degeneration remains unresolved. A new study has modeled TDP
      43 age-dependent axonal death in the Drosophila leg and used a powerful forward
      genetic screen to identify three novel suppressor genes. 

PMID- 26294191
TI  - Catalysis on singly dispersed bimetallic sites.
AB  - A catalytic site typically consists of one or more atoms of a catalyst surface
      that arrange into a configuration offering a specific electronic structure for
      adsorbing or dissociating reactant molecules. The catalytic activity of adjacent
      bimetallic sites of metallic nanoparticles has been studied previously. An
      isolated bimetallic site supported on a non-metallic surface could exhibit a
      distinctly different catalytic performance owing to the cationic state of the
      singly dispersed bimetallic site and the minimized choices of binding
      configurations of a reactant molecule compared with continuously packed
      bimetallic sites. Here we report that isolated Rh1Co3 bimetallic sites exhibit a
      distinctly different catalytic performance in reduction of nitric oxide with
      carbon monoxide at low temperature, resulting from strong adsorption of two
      nitric oxide molecules and a nitrous oxide intermediate on Rh1Co3 sites and
      following a low-barrier pathway dissociation to dinitrogen and an oxygen atom.
      This observation suggests a method to develop catalysts with high selectivity. 

PMID- 26294192
TI  - Introduction: Goodness and Human Life.

PMID- 26294194
TI  - Switching wormlike micelles of selenium-containing surfactant using redox
      reaction.
AB  - A novel redox-switchable wormlike micellar system was developed based on a
      mixture of selenium-containing zwitterionic surfactant and commercially available
      anionic surfactant sodium dodecyl sulfate, which reversibly and quickly responds
      to H2O2 and vitamin C, and shows circulatory gel/sol transition, reflecting
      changes in aggregate morphology from entangled worms to vesicles. 

PMID- 26294193
TI  - Vitamin D, serum 25(OH)D, LL-37 and polymorphisms in a Canadian First Nation
      population with endemic tuberculosis.
AB  - BACKGROUND: Canadian First Nation populations have experienced endemic and
      epidemic tuberculosis (TB) for decades. Vitamin D-mediated induction of the host
      defence peptide LL-37 is known to enhance control of pathogens such as
      Mycobacterium tuberculosis. OBJECTIVE: Evaluate associations between serum levels
      of 25-hydroxy vitamin D (25(OH)D) and LL-37, in adult Dene First Nation
      participants (N = 34) and assess correlations with single nucleotide
      polymorphisms (SNPs) in the vitamin D receptor (VDR) and vitamin D binding
      protein (VDBP). DESIGN: Venous blood was collected from all participants at
      baseline (winter and summer) and in conjunction with taking vitamin D supplements
      (1,000 IU/day) (winter and summer). Samples were analysed using ELISA for
      concentrations of vitamin D and LL-37, and SNPs in the VDR and VDBP regions were
      genotyped. RESULTS: Circulating levels of 25(OH)D were not altered by vitamin D
      supplementation, but LL-37 levels were significantly decreased. VDBP and VDR SNPs
      did not correlate with serum concentrations of 25(OH)D, but LL-37 levels
      significantly decreased in individuals with VDBP D432E T/G and T/T, and with VDR
      SNP Bsm1 T/T genotypes. CONCLUSIONS: Our findings suggest that vitamin D
      supplementation may not be beneficial as an intervention to boost innate immune
      resistance to M. tuberculosis in the Dene population.

PMID- 26294195
TI  - A descriptive analysis of aspartate and alanine aminotransferase rise and fall
      following acetaminophen overdose.
AB  - CONTEXT: Risk prediction following acetaminophen (paracetamol, APAP) overdose is
      based on serum APAP, aspartate aminotransferase (AST), and alanine
      aminotransferase (ALT) levels. One recently proposed risk stratification tool,
      the APAPxAT multiplication product, uses either AST or ALT, whichever is higher,
      yet their interrelation is not well known following APAP-induced hepatic injury.
      OBJECTIVE: To describe the kinetics of AST and ALT release into and disappearance
      from the circulation following APAP overdose. MATERIALS AND METHODS: An
      observational case series of adult patients with peak AST or ALT > 100 IU/L
      attributable to APAP toxicity. Cases were identified by electronic search of
      hospital laboratory database and by discharge diagnosis corroborated by
      structured explicit medical record review. RESULTS: Of 68 cases identified (mean
      age (SD): 39 (18) years, 63% female, and 21% ethanol co-ingested), 28 (41%)
      developed hepatotoxicity (peak AST or ALT > 1000 IU/L), 28 (41%) coagulopathy
      (international normalized ratio or INR > 2), and 21 (31%) both. Three patients
      (4%) were transferred for liver transplantation and ultimately six (8.8%) died.
      Serum AST and ALT activity rose in a closely aligned 1:1 AST:ALT ratio, but fell
      at distinctly different rates: AST activity fell with a half-life (interquartile
      range [IQR]) of 15.1 (12.2, 19.4) hours, and ALT 39.6 (32.9, 47.6) hours. Using
      an aminotransferase falling to below 50% of peak as the basis for discontinuing
      acetylcysteine would have resulted in antidotal treatment being stopped 24 (IQR:
      9.6, 40) hours earlier (and in no cases later) using AST rather than ALT. Only
      six patients had an AST:ALT ratio greater than 2:1 at the time of acetylcysteine
      administration; of these six, four died and one survivor developed coagulopathy.
      DISCUSSION: AST and ALT release into the circulation appears tightly linked and
      numerically similar, except in the sickest patients. Once the aminotransferases
      peak, AST returns to baseline more quickly. CONCLUSION: Either AST or ALT can be
      used for early risk stratification tools when only one is known. Any criterion
      for N-AC discontinuation should be based on the decline of AST rather than ALT,
      with a potential benefit measured in days.

PMID- 26294196
TI  - Molecular bio-dosimetry for carcinogenic risk assessment in survivors of Bhopal
      gas tragedy.
AB  - December 2014 marked the 30th year anniversary of Bhopal gas tragedy. This sudden
      and accidental leakage of deadly poisonous methyl isocyanate (MIC) gas instigated
      research efforts to understand the nature, severity of health damage and
      sufferings of 570 000 ailing survivors of this tragedy. In a decade-long period,
      our systematic laboratory investigations coupled with long-term molecular
      surveillance studies have comprehensively demonstrated that the risk of
      developing an environmental associated aberrant disease phenotype, including
      cancer, involves complex interplay of genomic and epigenetic reprogramming. These
      findings poised us to translate this knowledge into an investigative framework of
      "molecular biodosimetry" in a strictly selected cohort of MIC exposed
      individuals. A pragmatic cancer risk-assessment strategy pursued in concert with
      a large-scale epidemiological study might unfold molecular underpinnings of host
      susceptibility and exposureresponse relationship. The challenges are enormous,
      but we postulate that the study will be necessary to establish a direct
      initiation-promotion paradigm of environmental carcinogenesis. Given that
      mitochondrial retrograde signaling-induced epigenetic reprogramming is apparently
      linked to neoplasticity, a cutting-edge tailored approach by an expert pool of
      biomedical researchers will be fundamental to drive these strategies from
      planning to execution. Validating the epigenomic signatures will hopefully result
      in the development of biomarkers to better protect human lives in an overburdened
      ecosystem, such as India, which is continuously challenged to meet population
      demands. Besides, delineating the mechanistic links between MIC exposure and
      cancer morbidity, our investigative strategy might help to formulate suitable
      regulatory policies and measures to reduce the overall burden of occupational and
      environmental carcinogenesis. 

PMID- 26294197
TI  - Application of eye-tracking in the testing of drivers: A review of research.
AB  - Recording and analyzing eye movements provide important elements for
      understanding the nature of the task of driving a vehicle. This article reviews
      the literature on eye movement strategies employed by drivers of vehicles
      (vehicle control, evaluation of the situation by analyzing essential visual
      elements, navigation). Special focus was placed on the phenomenon of conspicuity,
      the probability of perceiving an object in the visual field and the factors that
      determine it. The article reports the methods of oculographic examination, with
      special emphasis on the non-invasive technique using corneal reflections, and the
      criteria for optimal selection of the test apparatus for drivers in experimental
      conditions (on a driving simulator) and in real conditions. Particular attention
      was also paid to the helmet - or glass-type devices provided with 1 or 2 high
      definition (HD) camcorders recording the field of vision and the direction of
      gaze, and the non-contact devices comprising 2 or 3 cameras and an infrared
      source to record eye and head movements, pupil diameter, eye convergence
      distance, duration and frequency of eyelid blinking. A review of the studies
      conducted using driver eye-tracking procedure was presented. The results, in
      addition to their cognitive value, can be used with success to optimize the
      strategy of drivers training. 

PMID- 26294198
TI  - Meconium samples used to assess infant exposure to the components of ETS during
      pregnancy.
AB  - OBJECTIVES: The aim of the study was to use meconium samples to assess fetal
      exposure to compounds present in environmental tobacco smoke (ETS). MATERIAL AND
      METHODS: In order to assess fetal exposure to toxic tobacco smoke compounds,
      samples of meconium from the offspring of women with different levels of tobacco
      smoke exposure, and the samples of saliva from the mothers were analyzed.
      Thiocyanate ion as a biomarker of tobacco smoke exposure, and other ions that are
      indices of such exposure were determined by means of ion chromatography. RESULTS:
      The results of ion chromatography analysis of the meconium and maternal saliva
      samples for the presence of cations and anions (including thiocyanate ion)
      indicate that the concentration level of specific ions depends on the intensity
      of environmental tobacco smoke exposure of pregnant women. CONCLUSIONS: Based on
      the results, it can be concluded that meconium samples can be used to determine
      the substances from tobacco smoke. The results confirm the effect of smoking
      during pregnancy on the presence and content of substances from tobacco smoke.

PMID- 26294199
TI  - Preliminary study to explore gene-PM2.5 interactive effects on respiratory system
      in traffic policemen.
AB  - OBJECTIVES: Traffic-related particulate matter (PM) is one of the major sources
      of air pollution in metropolitan areas. This study is to observe the interactive
      effects of gene and fine particles (particles smaller than 2.5 MUm - PM2.5) on
      the respiratory system and explore the mechanisms linking PM2.5 and pulmonary
      injury. MATERIAL AND METHODS: The participants include 110 traffic policemen and
      101 common populations in Shanghai, China. Continuous 24 h individual-level PM2.5
      is detected and the pulmonary function, high-sensitivity C-reactive protein (hs
      CRP), Clara cell protein 16 (CC16) and the polymorphism in CXCL3, NME7 and C5
      genes are determined. The multiple linear regression method is used to analyze
      the association between PM2.5 and health effects. Meanwhile, the interactive
      effects of gene and PM2.5 on lung function are analyzed. RESULTS: The individual
      PM2.5 exposure for traffic policemen was higher than that in the common
      population whereas the forced expiratory volume in 1 s (FEV1), the ratio of FEV1
      to forced vital capacity (FEV1/FVC) and lymphocytes are lower. In contrast, the
      hs-CRP level is higher. In the adjusted analysis, PM2.5 exposure was associated
      with the decrease in lymphocytes and the increase in hs-CRP. The allele
      frequencies for NME7 and C5 have significant differences between FEV1/FVC <= 70%
      and FEV1/FVC > 70% participants. The results didn't find the interaction effects
      of gene and PM2.5 on FEV1/FVC in all the 3 genes. CONCLUSIONS: The results
      indicated that traffic exposure to high levels of PM2.5 was associated with
      systemic inflammatory response and respiratory injury. Traffic policemen
      represent a high risk group suffering from the respiratory injury.

PMID- 26294200
TI  - Occupational exposure to diisocyanates in polyurethane foam factory workers.
AB  - OBJECTIVES: The aim of the study was to evaluate health effects of occupational
      exposure to diisocyanates (DIC) among polyurethane foam products factory workers.
      MATERIAL AND METHODS: Thirty workers had a physical examination, skin prick tests
      with common allergens, allergen-specific immunoglobulin E (IgE) antibodies to
      diisocyanates and pulmonary function tests. Concentrations of selected
      isocyanates in the workplace air samples as well as concentration of their
      metabolites in the urine samples collected from the workers of the plant were
      determined. RESULTS: The most frequent work-related symptoms reported by the
      examined subjects were rhinitis and skin symptoms. Sensitization to at least 1
      common allergen was noted in 26.7% of the subjects. Spirometry changes of
      bronchial obstruction of a mild degree was observed in 5 workers. The specific
      IgE antibodies to toluene diisocyanate (TDI) and 4,4'-methylenebis(phenyl
      isocyanate) (MDI) were not detected in any of the patients' serum. Cellular
      profiles of the collected induced sputum (ISP) did not reveal any abnormalities.
      Air concentrations of TDI isomers ranged 0.2-58.9 MUg/m3 and in 7 cases they
      exceeded the Combined Exposure Index (CEI) value for those compounds.
      Concentrations of TDI metabolites in post-shift urine samples were significantly
      higher than in the case of pre-shift urine samples and in 6 cases they exceeded
      the British Biological Monitoring Guidance Value (BMGV - 1 MUmol amine/mol
      creatinine). We didn't find a correlation between urinary concentrations of TDI,
      concentrations in the air and concentrations of toluenediamine (TDA) in the post
      shift urine samples. Lack of such a correlation may be an effect of the
      respiratory protective equipment use. CONCLUSIONS: Determination of specific IgE
      in serum is not sensitive enough to serve as a biomarker. Estimation of
      concentrations of diisocyanate metabolites in urine samples and the presence of
      work-related allergic symptoms seem to be an adequate method for occupational
      exposure monitoring of DIC, which may help to determine workers at risk as well
      as to recognize hazardous workplaces.

PMID- 26294201
TI  - Re-initiating professional working activity after myocardial infarction in
      primary percutaneous coronary intervention networks era.
AB  - OBJECTIVES: To investigate the aspects of return to work, socio-economic and
      quality of life aspects in 145 employed patients under 60 years of age treated
      with primary percutaneous coronary intervention for acute ST-elevation myocardial
      infarction. MATERIAL AND METHODS: During hospital treatment demographic and
      clinical data was collected. Data about major adverse cardiovascular events,
      rehabilitation, sick leave, discharge from job and retirement, salary, major life
      events and estimation of quality of life after myocardial infarction were
      obtained after follow-up (mean: 836+/-242 days). RESULTS: Average sick leave was
      126+/-125 days. Following myocardial infarction, 3.4% of patients were discharged
      from their jobs while 31.7% retired. Lower salary was reported in 17.9% patients,
      major life events in 9.7%, while 40.7% estimated quality of life as worse
      following the event. Longer hospitalization was reported in patients transferred
      from surrounding counties, those with inferior myocardial wall and right coronary
      artery affected. Age, hyperlipoproteinemia and lower education degree were
      connected to permanent working cessation. Significant salary decrease was
      observed in male patients. Employer type was related to sick leave duration.
      Impaired quality of life was observed in patients who underwent in-hospital
      rehabilitation and those from surrounding counties. Longer sick leave was
      observed in patients with lower income before and after myocardial infarction.
      These patients reported lower quality of life after myocardial infarction.
      CONCLUSIONS: Inadequate health policy and delayed cardiac rehabilitation after
      myocardial infarction may lead to prolonged hospitalization and sick leave as
      well as lower quality of life after the event, regardless of optimal treatment in
      acute phase of disease.

PMID- 26294202
TI  - Association between sleep duration and sleep quality, and metabolic syndrome in
      Taiwanese police officers.
AB  - OBJECTIVES: This study's objective was to examine association between sleep
      duration and sleep quality, and metabolic syndrome (MetS) and its components in
      Taiwanese male police officers. MATERIAL AND METHODS: Male police officers who
      underwent annual health examinations were invited to join the study and
      eventually a total of 796 subjects was included in it. The study subjects were
      divided into 5 groups according to the length (duration) of sleep: < 5, 5-5.9, 6
      6.9, 7-7.9 and >= 8 h per day, and the global Pittsburgh Sleep Quality Index was
      used to categorize their sleep quality as good or poor. To analyze the
      association between sleep problems and MetS, adjusted odds ratio and respective
      95% confidence intervals (CI) were computed. RESULTS: The prevalence of MetS in
      Taiwanese male police officers was 24.5%. Abdominal obesity had the highest
      proportion (36.2%) among 5 components of MetS. More than 1/2 of the police
      officers (52.3%) had poor sleep quality. Police officers with higher scores of
      sleep disturbances had a higher prevalence of MetS (p = 0.029) and abdominal
      obesity (p = 0.009). After adjusting for age, low-density lipoprotein
      cholesterol, smoking status, alcohol drinking habit, physical habitual exercise,
      snoring and type of shift work, the police officers who slept less than 5 h were
      88% more likely to suffer from abdominal obesity than those who slept 7-7.9 h
      (95% CI: 1.01-3.5). Sleep quality was not associated with MetS and its
      components. CONCLUSIONS: The police officers who slept less than 5 h were more
      likely to experience abdominal obesity in Taiwan, and those with higher scores of
      sleep disturbances had a higher prevalence of MetS and abdominal obesity. It is
      recommended that police officers with short sleep duration or sleep disturbances
      be screened for MetS and waist circumference in order to prevent cardiovascular
      diseases.

PMID- 26294203
TI  - The prevalence of asthma work relatedness: Preliminary data.
AB  - OBJECTIVES: About 5-10% of asthmatics do not respond well to standard treatment
      plan. Occupational exposure may be one of the factors that can be linked with
      treatment failure. The aim of the study was to assess the prevalence of work
      related asthma (WRA) among adult asthmatics under follow up in an outpatient
      allergy clinic and to create a useful tool for detecting individuals with
      possible WRA. MATERIAL AND METHODS: Preliminary 5-question questionnaire designed
      to recognize WRA was presented to 300 asthmatics. All patients with positive
      preliminary verification along with 50 subjects from control group were asked to
      fill up a detailed questionnaire. The WRA was diagnosed by positive match for
      asthma symptoms in combination with workplace exposure indicated in the detailed
      WRA questionnaire followed by confirmation of each WRA case by detailed exposure
      analysis. RESULTS: Work-related asthma was recognized in 63 subjects (21% of
      study group). The preliminary questionnaire has 76.9% sensitivity and 94%
      specificity in recognition of WRA. Occupational exposure to irritants is a risk
      factor of WRA recognition (relative risk (RR) = 2.09 (1.44:3.03)). Working in
      exposure-free environment is a factor against WRA recognition (RR = 0.38
      (0.24:0.61)). Among subjects with work-related asthma, the uncontrolled course of
      the disease is significantly more frequent (p = 0.012). Subjects with WRA more
      often report sickness absenteeism due to asthma than those without WRA (9.6% vs.
      3.2%, respectively), but the observed differences did not reach the statistical
      significance. CONCLUSIONS: Short 5-question questionnaire seems to be a promising
      tool to detect individuals with possible work-related asthma in the outpatient
      setting for further evaluation and additional attention.

PMID- 26294204
TI  - Broken heart as work-related accident: Occupational stress as a cause of
      takotsubo cardiomyopathy in 55-year-old female teacher - Role of automated
      function imaging in diagnostic workflow.
AB  - Takotsubo cardiomiopathy (TTC) (known also as "ampulla cardiomyopathy," "apical
      ballooning" or "broken heart syndrome") is connected with a temporary systolic
      left ventricular dysfunction without the culprit coronary lesion. Takotsubo
      cardiomyopathy was first described in 1990 in Japan after octopus trapping pot
      with a round bottom and narrow neck similar in shape to left ventriculogram in
      TTC patients. The occurrence of TTC is usually precipitated by a stressful event
      with a clinical presentation mimicking myocardial infarction: chest pain, ST-T
      segment elevation or T-wave inversion, a rise in cardiac troponin, and
      contractility abnormalities in echocardiography. A left ventricular dysfunction
      is transient and improves within a few weeks. Takotsubo cardiomyopathy typically
      occurs in postmenopausal women and the postulated mechanism is catecholamine
      overstimulation. Moreover, the distribution of contractility impairments usually
      does not correspond with typical region supplied by a single coronary artery.
      Therefore, the assessment of regional pattern of systolic dysfunction with
      speckle-tracking echocardiography and automated function imaging (AFI) technique
      may be important in diagnosis of TTC and may improve our insight into its
      patophysiology. We described a 55-year-old female teacher with TTC diagnosed
      after acute psychological stress in workplace. The provoking factor related with
      occupational stress and pattern of contraction abnormalities documented with AFI
      technique including basal segments of left ventricle make this case atypical. 

PMID- 26294205
TI  - Assessment of foetal wellbeing in pregnant women subjected to pelvic floor muscle
      training: a controlled randomised study.
AB  - INTRODUCTION AND HYPOTHESIS: The objective was to assess foetal wellbeing in
      pregnant women subjected to pelvic floor muscle training (PFMT) by evaluating the
      acute and chronic effects of the procedure using the Doppler method. METHODS:
      Ninety-six primigravidae with singleton pregnancies and at a low risk of
      pregnancy complications were randomised to either intervention with PFMT or no
      intervention. The final analysis included 26 women in the intervention group and
      33 in the control group. Women from the intervention group were subjected to a
      daily PFMT program. Evidence of possible foetal risk was assessed by Doppler and
      the control group received standard care. The protocol was conducted from 20 to
      36 weeks' gestation. The pulsatility indices (PI) of the uterine, umbilical and
      middle cerebral arteries were determined at 28, 32 and 36 weeks' gestation. The
      acute effects were determined by comparing the values obtained before and after
      exercise in the group subjected to PFMT and the chronic effects were determined
      by comparing the resting values of the trained group with those of the control
      group. RESULTS: The results obtained showed normal values for the three
      gestational ages in both groups, with no difference between groups. Comparison
      before and after exercise showed a significant decline in the PI of uterine
      artery at 36 weeks without changes in the flow of umbilical and middle cerebral
      arteries. CONCLUSION: Pelvic floor muscle training in low-risk primigravidae with
      singleton pregnancies was associated with a significant decline in PI of the
      uterine artery after exercise, while no significant changes in the flow of the
      middle cerebral and umbilical arteries were found. The PFMT may be recommended to
      women as a first-line measure to prevent of urinary incontinence during
      pregnancy.

PMID- 26294206
TI  - Assessing the learning curve of robotic sacrocolpopexy.
AB  - INTRODUCTION AND HYPOTHESIS: The aim was to evaluate the learning curve of
      robotic sacrocolpopexy, adjusted for surgical risk. METHODS: The charts of 145
      robotic sacrocolpopexies performed by urogynecologists at Mayo Clinic, Rochester,
      MN, USA, from 2007 to 2013, were reviewed. Outcomes of interest included
      operative time, intraoperative complications, and postoperative complications
      with a Clavien-Dindo grade 2 or higher. Risk-adjusted cumulative summation
      analysis was performed by comparing a calculated complication risk score with
      observed patient outcomes, and then cumulatively recalculating the rate of
      expected vs observed complications after each procedure. Proficiency was defined
      as the point at which the surgeon's complication rates were better than expected,
      given the patient's risk factors. RESULTS: The median operative time decreased
      significantly, from 5.3 to 3.6 h, during the 7-year period, and plateaued after
      the first 60 cases. A higher ASA classification was associated with an increased
      risk of intraoperative complications (p = 0.02), and a higher Charlson
      comorbidity index was associated with an increased risk of intraoperative or
      postoperative complications (p = 0.01). In risk-adjusted CUSUM analyses,
      accounting for these factors, and for body-mass index and vaginal parity,
      proficiency was identified at 55 cases for intraoperative complications and 84
      cases for intraoperative or postoperative complications. CONCLUSIONS: Operative
      time plateaued after the first 60 cases, whereas complication rates continued to
      decrease beyond this. Proficiency, as determined by a risk-adjusted CUSUM
      analysis for complication rates, was achieved after approximately 84 cases.
      Evaluation of postoperative complications in addition to intraoperative
      complications, in a risk-adjusted model, is critical in depicting the surgical
      learning curve.

PMID- 26294207
TI  - Effect of vaginal infiltration with ornipressin or saline on intraoperative blood
      loss during vaginal prolapse surgery: a randomised controlled trial.
AB  - INTRODUCTION AND HYPOTHESIS: Hydrodissection incorporating different types of
      vasoconstrictors is commonly used in vaginal prolapse surgery. There is little
      evidence as to whether it adds clinical value or whether it exposes the patient
      to unnecessary risk. The aim of this study was to compare the effect of a
      vasoconstrictor compared with saline alone on operative blood loss and
      cardiovascular parameters in a randomised clinical trial setting. METHODS:
      Patients undergoing vaginal prolapse surgery were randomised to an ornipressin
      (Por-8, Ferring) solution or saline alone for hydrodissection. The surgeon and
      patient were blinded to the solution used. Operative blood loss was accurately
      quantified and blood pressure and pulse readings recorded Pre, intra- and
      postoperatively. RESULTS: Eighty women were randomised. There was a statistically
      significant difference in the median blood loss: 35 ml (1-209 ml) in the
      ornipressin group compared with 81 ml (2-328 ml) in the saline group, p = 0.03.
      There was no statistically significant difference in the median pre and
      postoperative blood pressure or pulse rate between groups. CONCLUSIONS: The use
      of a vasoconstrictor (ornipressin) resulted in a statistically significant
      decrease in operative blood loss during vaginal prolapse surgery. This occurred
      without any significant changes in measured cardiovascular parameters.

PMID- 26294208
TI  - Gold standard: a failed concept.

PMID- 26294210
TI  - The Neuronal Pentraxin-2 Pathway Is an Unrecognized Target in Human
      Neuroblastoma, Which Also Offers Prognostic Value in Patients.
AB  - Neuronal pentraxins (NPTX) and their corresponding receptors (NPTXR) have been
      studied as synapse-associated proteins in the nervous system, but their role in
      cancer is largely unknown. By applying a multidisciplinary, high-throughput
      proteomic approach, we have recently identified a peptide ligand motif for
      targeted drug delivery to neuroblastoma. Here, we report the sequence similarity
      between this peptide and a conserved portion of the pentraxin domain that is
      involved in the homo- and hetero-oligomerization of NPTX2 and NPTXR. We show
      that, in comparison with normal tissues, NPTX2 and NPTXR are overexpressed in
      vivo in mouse models, as well as in human Schwannian stroma-poor, stage IV
      neuroblastoma. Both proteins are concentrated in the vicinity of tumor blood
      vessels, with NPTXR also present on neuroblastic tumor cells. In vivo targeting
      of NPTX2 and NPTXR with the selected peptide or with specific antibodies reduces
      tumor burden in orthotopic mouse models of human neuroblastoma. In vitro
      interference with this ligand/receptor system inhibits the organization of
      neuroblastoma cells in tumor-like masses in close contact with vascular cells, as
      well as their adhesion to normal microenvironment-derived cells, suggesting a
      role in the cross-talk between tumor and normal cells in the early steps of
      neuroblastoma development. Finally, we show that NPTX2 is a marker of poor
      prognosis for neuroblastoma patients.

PMID- 26294209
TI  - CD38-Expressing Myeloid-Derived Suppressor Cells Promote Tumor Growth in a Murine
      Model of Esophageal Cancer.
AB  - Myeloid-derived suppressor cells (MDSC) are an immunosuppressive population of
      immature myeloid cells found in advanced-stage cancer patients and mouse tumor
      models. Production of inducible nitric oxide synthase (iNOS) and arginase, as
      well as other suppressive mechanisms, allows MDSCs to suppress T-cell-mediated
      tumor clearance and foster tumor progression. Using an unbiased global gene
      expression approach in conditional p120-catenin knockout mice (L2
      cre;p120ctn(f/f)), a model of oral-esophageal cancer, we have identified CD38 as
      playing a vital role in MDSC biology, previously unknown. CD38 belongs to the ADP
      ribosyl cyclase family and possesses both ectoenzyme and receptor functions. It
      has been described to function in lymphoid and early myeloid cell
      differentiation, cell activation, and neutrophil chemotaxis. We find that CD38
      expression in MDSCs is evident in other mouse tumor models of esophageal
      carcinogenesis, and CD38(high) MDSCs are more immature than MDSCs lacking CD38
      expression, suggesting a potential role for CD38 in the maturation halt found in
      MDSC populations. CD38(high) MDSCs also possess a greater capacity to suppress
      activated T cells, and promote tumor growth to a greater degree than CD38(low)
      MDSCs, likely as a result of increased iNOS production. In addition, we have
      identified novel tumor-derived factors, specifically IL6, IGFBP3, and CXCL16,
      which induce CD38 expression by MDSCs ex vivo. Finally, we have detected an
      expansion of CD38(+) MDSCs in peripheral blood of advanced-stage cancer patients
      and validated targeting CD38 in vivo as a novel approach to cancer therapy.

PMID- 26294211
TI  - Androgen-Regulated SPARCL1 in the Tumor Microenvironment Inhibits Metastatic
      Progression.
AB  - Prostate cancer is a leading cause of cancer death in men due to the subset of
      cancers that progress to metastasis. Prostate cancers are thought to be hardwired
      to androgen receptor (AR) signaling, but AR-regulated changes in the prostate
      that facilitate metastasis remain poorly understood. We previously noted a marked
      reduction in secreted protein, acidic and rich in cysteine-like 1 (SPARCL1)
      expression during invasive phases of androgen-induced prostate growth, suggesting
      that this may be a novel invasive program governed by AR. Herein, we show that
      SPARCL1 loss occurs concurrently with AR amplification or overexpression in
      patient-based data. Mechanistically, we demonstrate that SPARCL1 expression is
      directly suppressed by androgen-induced AR activation and binding at the SPARCL1
      locus via an epigenetic mechanism, and these events can be pharmacologically
      attenuated with either AR antagonists or HDAC inhibitors. We establish using the
      Hi-Myc model of prostate cancer that in Hi-Myc/Sparcl1(-/-) mice, SPARCL1
      functions to suppress cancer formation. Moreover, metastatic progression of Myc
      CaP orthotopic allografts is restricted by SPARCL1 in the tumor microenvironment.
      Specifically, we show that SPARCL1 both tethers to collagen in the extracellular
      matrix (ECM) and binds to the cell's cytoskeleton. SPARCL1 directly inhibits the
      assembly of focal adhesions, thereby constraining the transmission of cell
      traction forces. Our findings establish a new insight into AR-regulated prostate
      epithelial movement and provide a novel framework whereby SPARCL1 in the ECM
      microenvironment restricts tumor progression by regulating the initiation of the
      network of physical forces that may be required for metastatic invasion of
      prostate cancer.

PMID- 26294214
TI  - Akt Kinase-Interacting Protein 1 Signals through CREB to Drive Diffuse Malignant
      Mesothelioma.
AB  - Diffuse malignant mesothelioma (DMM) is a tumor of serosal membranes with
      propensity for progressive local disease. Because current treatment options are
      largely ineffective, novel therapeutic strategies based on molecular mechanisms
      and the disease characteristics are needed to improve the outcomes of patients
      with this disease. Akt kinase interacting protein 1 (Aki1; Freud-1/CC2D1A) is a
      scaffold protein for the PI3K-PDK1-Akt signaling module that helps determine
      receptor signal selectivity for EGFR. Aki1 has been suggested as a therapeutic
      target, but its potential has yet to be evaluated in a tumor setting. Here, we
      report evidence supporting its definition as a therapeutic target in DMM. In cell
      based assays, Aki1 silencing decreased cell viability and caused cell-cycle
      arrest of multiple DMM cell lines via effects on the PKA-CREB1 signaling pathway.
      Blocking CREB activity phenocopied Aki1 silencing. Clinically, Aki1 was expressed
      in most human DMM specimens where its expression correlated with phosphorylated
      CREB1. Notably, Aki1 siRNA potently blocked tumor growth in an orthotopic
      implantation model of DMM when administered directly into the pleural cavity of
      tumor-bearing mice. Our findings suggest an important role for the Aki1-CREB axis
      in DMM pathogenesis and provide a preclinical rationale to target Aki1 by
      intrathoracic therapy in locally advanced tumors.

PMID- 26294212
TI  - Hypoxia Drives Breast Tumor Malignancy through a TET-TNFalpha-p38-MAPK Signaling
      Axis.
AB  - Hypoxia is a hallmark of solid tumors that drives malignant progression by
      altering epigenetic controls. In breast tumors, aberrant DNA methylation is a
      prevalent epigenetic feature associated with increased risk of metastasis and
      poor prognosis. However, the mechanism by which hypoxia alters DNA methylation or
      other epigenetic controls that promote breast malignancy remains poorly
      understood. We discovered that hypoxia deregulates TET1 and TET3, the enzymes
      that catalyze conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine
      (5hmC), thereby leading to breast tumor-initiating cell (BTIC) properties. TET1/3
      and 5hmC levels were closely associated with tumor hypoxia, tumor malignancy, and
      poor prognosis in breast cancer patients. Mechanistic investigations showed that
      hypoxia leads to genome-wide changes in DNA hydroxymethylation associated with
      upregulation of TNFalpha expression and activation of its downstream p38-MAPK
      effector pathway. Coordinate functions of TET1 and TET3 were also required to
      activate TNFalpha-p38-MAPK signaling as a response to hypoxia. Our results reveal
      how signal transduction through the TET-TNFalpha-p38-MAPK signaling axis is
      required for the acquisition of BTIC characteristics and tumorigenicity in vitro
      and in vivo, with potential implications for how to eradicate BTIC as a
      therapeutic strategy.

PMID- 26294216
TI  - Middle Cerebral Artery Occlusion Presenting as Upper Limb Monochorea.
AB  - BACKGROUND: Hemichorea is usually caused by a structural lesion in the
      contralateral basal ganglia or subthalamic nuclei or it develops as a form of a
      neurologic complication including hyperglycemia. We report a rare case of a
      patient who developed choreic movement in the right upper extremity associated
      with a contralateral middle cerebral artery (MCA) occlusion. METHODS: A 76-year
      old man presented with chorea in the right upper limb, known as monochorea, which
      occurred after recovery from losing consciousness while standing. He was found to
      have idiopathic orthostatic hypotension. His diffusion-weighted magnetic
      resonance imaging did not show signal changes indicative of acute ischemic
      lesions. A left carotid artery angiogram showed occlusion of the left MCA. (123)I
      N-isopropyl-4-iodoamphetamine single-photon emission computed tomography of the
      brain showed marked hypoperfusion in the left MCA territory. His cerebrovascular
      reserve capacity determined using acetazolamide was relatively decreased in this
      territory. This decrease in cerebrovascular reserve capacity, however, did not
      require surgical treatment, such as extracranial-intracranial bypass surgery.
      RESULTS: The recurrence of chorea was not observed after antiplatelet therapy and
      instruction on how to cope with orthostatic hypotension. CONCLUSIONS: It is
      considered that transient hemodynamic ischemia in the right basal ganglia
      thalamocortical circuits because of the combination of MCA occlusion and
      hypotension was the underlying cause of the monochorea in this patient.Vascular
      imaging studies for early identification of occlusion or severe stenosis of
      cerebral major arteries should be carried out in patients acutely presenting with
      chorea, even in the absence of other clinical signs.

PMID- 26294213
TI  - Notch1 Activation or Loss Promotes HPV-Induced Oral Tumorigenesis.
AB  - Viral oncogene expression is insufficient for neoplastic transformation of human
      cells, so human papillomavirus (HPV)-associated cancers will also rely upon
      mutations in cellular oncogenes and tumor suppressors. However, it has been
      difficult so far to distinguish incidental mutations without phenotypic impact
      from causal mutations that drive the development of HPV-associated cancers. In
      this study, we addressed this issue by conducting a functional screen for genes
      that facilitate the formation of HPV E6/E7-induced squamous cell cancers in mice
      using a transposon-mediated insertional mutagenesis protocol. Overall, we
      identified 39 candidate driver genes, including Notch1, which unexpectedly was
      scored by gain- or loss-of-function mutations that were capable of promoting
      squamous cell carcinogenesis. Autochthonous HPV-positive oral tumors possessing
      an activated Notch1 allele exhibited high rates of cell proliferation and tumor
      growth. Conversely, Notch1 loss could accelerate the growth of invasive tumors in
      a manner associated with increased expression of matrix metalloproteinases and
      other proinvasive genes. HPV oncogenes clearly cooperated with loss of Notch1,
      insofar as its haploinsufficiency accelerated tumor growth only in HPV-positive
      tumors. In clinical specimens of various human cancers, there was a consistent
      pattern of NOTCH1 expression that correlated with invasive character, in support
      of our observations in mice. Although Notch1 acts as a tumor suppressor in mouse
      skin, we found that oncogenes enabling any perturbation in Notch1 expression
      promoted tumor growth, albeit via distinct pathways. Our findings suggest caution
      in interpreting the meaning of putative driver gene mutations in cancer, and
      therefore therapeutic efforts to target them, given the significant contextual
      differences in which such mutations may arise, including in virus-associated
      tumors.

PMID- 26294215
TI  - Small-Molecule NSC59984 Restores p53 Pathway Signaling and Antitumor Effects
      against Colorectal Cancer via p73 Activation and Degradation of Mutant p53.
AB  - The tumor-suppressor p53 prevents cancer development via initiating cell-cycle
      arrest, cell death, repair, or antiangiogenesis processes. Over 50% of human
      cancers harbor cancer-causing mutant p53. p53 mutations not only abrogate its
      tumor-suppressor function, but also endow mutant p53 with a gain of function
      (GOF), creating a proto-oncogene that contributes to tumorigenesis, tumor
      progression, and chemo- or radiotherapy resistance. Thus, targeting mutant p53 to
      restore a wild-type p53 signaling pathway provides an attractive strategy for
      cancer therapy. We demonstrate that small-molecule NSC59984 not only restores
      wild-type p53 signaling, but also depletes mutant p53 GOF. NSC59984 induces
      mutant p53 protein degradation via MDM2 and the ubiquitin-proteasome pathway.
      NSC59984 restores wild-type p53 signaling via p73 activation, specifically in
      mutant p53-expressing colorectal cancer cells. At therapeutic doses, NSC59984
      induces p73-dependent cell death in cancer cells with minimal genotoxicity and
      without evident toxicity toward normal cells. NSC59984 synergizes with CPT11 to
      induce cell death in mutant p53-expressing colorectal cancer cells and inhibits
      mutant p53-associated colon tumor xenograft growth in a p73-dependent manner in
      vivo. We hypothesize that specific targeting of mutant p53 may be essential for
      anticancer strategies that involve the stimulation of p73 in order to efficiently
      restore tumor suppression. Taken together, our data identify NSC59984 as a
      promising lead compound for anticancer therapy that acts by targeting GOF-mutant
      p53 and stimulates p73 to restore the p53 pathway signaling.

PMID- 26294217
TI  - Risk Factors for Multiple Myeloma: A Systematic Review of Meta-Analyses.
AB  - The epidemiology of multiple myeloma (MM) is an increasingly investigated field,
      with many controversies. This systematic review aims to synthesize meta-analyses
      examining risk factors for MM so as to provide a comprehensive, parsimonious
      summary of the current evidence. Eligible meta-analyses were sought in PubMed
      adopting a predefined algorithm, without any restriction of publication language;
      end-of-search date was October 10, 2014. The selection of eligible studies and
      data extraction were performed by working in pairs, independently and blindly to
      each other; in case of disagreement, consensus with the whole team was reached.
      Among the 22 ultimately included meta-analyses, 9 examined occupational factors,
      4 assessed aspects of lifestyle (smoking, alcohol, body mass index), 5 evaluated
      the presence of other diseases, and 4 addressed genetic factors as potential risk
      factors of MM. A vast compendium of significant associations arose, including
      farming, occupation as a firefighter, occupation as a hairdresser, exposures to
      chemicals or pesticides, overweight and obesity, patterns of alcohol intake,
      pernicious anemia, ankylosing spondylitis, gene promoter methylation, and
      polymorphisms. In conclusion, MM is a multifactorial disease, encompassing a wide
      variety of risk factors that span numerous life aspects. Further accumulation of
      evidence through meta-analyses is anticipated in this rapidly growing field. 

PMID- 26294218
TI  - Does facilitated Advance Care Planning reduce the costs of care near the end of
      life? Systematic review and ethical considerations.
AB  - BACKGROUND: While there is increasing evidence that Advance Care Planning has the
      potential to strengthen patient autonomy and improve quality of care near the end
      of life, it remains unclear whether it could also reduce net costs of care. AIM:
      This study aims to describe the cost implications of Advance Care Planning
      programmes and discusses ethical conflicts arising in this context. DESIGN: We
      conducted a systematic review based on the Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses statement. DATA SOURCES: We systematically
      searched the databases PubMed, NHS EED, EURONHEED, Cochrane Library and EconLit.
      We included empirical studies (no limitation to study type) that investigated the
      cost implications of Advance Care Planning programmes involving professionally
      facilitated end-of-life discussions. RESULTS AND DISCUSSION: Seven studies met
      our inclusion criteria. Four of them used a randomised controlled design, one
      used a before-after design and two were observational studies. Six studies found
      reductions in costs of care ranging from USD1041 to USD64,827 per patient,
      depending on the study period and the cost measurement. One study detected no
      differences in costs. Studies varied considerably regarding the Advance Care
      Planning intervention, patient selection and costs measured which may explain
      some of the variations in findings. NORMATIVE APPRAISAL: Looking at the impact of
      Advance Care Planning on costs raises delicate ethical issues. Given the
      increasing pressure to reduce expenditures, there may be concerns that cost
      considerations could unduly influence the sensitive communication process, thus
      jeopardising patient autonomy. Safeguards are proposed to reduce these risks.
      CONCLUSION: The limited data indicate net cost savings may be realised with
      Advance Care Planning. Methodologically robust trials with clearly defined
      Advance Care Planning interventions are needed to make the costs and returns of
      Advance Care Planning transparent.

PMID- 26294219
TI  - PET/CT versus conventional CT for detection of lymph node metastases in patients
      with locally advanced bladder cancer.
AB  - BACKGROUND: We studied patients treated with radical cystectomy for locally
      advanced bladder cancer to compare the results of both preoperative positron
      emission tomography/computed tomography (PET/CT) and conventional CT with the
      findings of postoperative histopathological evaluation of lymph nodes. METHODS:
      Patients who had bladder cancer and were candidates for cystectomy underwent
      preoperative PET/CT using 18-fluorodeoxyglucose (FDG) and conventional CT. The
      results regarding lymph node involvement were independently evaluated by two
      experienced radiologists and were subsequently compared with histopathology
      results, the latter of which were reassessed by an experienced uropathologist
      (HO). RESULTS: There were 54 evaluable patients (mean age 68 years, 47 [85%]
      males and 7 [15%] females) with pT and pN status as follows: < pT2-14 (26%), pT2
      10 (18%), and > pT2-30 (56%); pN0 37 (69%) and pN+ 17 (31%). PET/CT showed
      positive lymph nodes in 12 patients (22%), and 7 of those cases were confirmed by
      histopathology; the corresponding results for conventional CT were 11 (20%) and 7
      patients (13%), respectively. PET/CT had 41% sensitivity, 86% specificity, 58%
      PPV, and 76% NPV, whereas the corresponding figures for conventional CT were 41%,
      89%, 64%, and 77%. Additional analyses of the right and left side of the body or
      in specified anatomical regions gave similar results. CONCLUSIONS: In this study,
      PET/CT and conventional CT had similar low sensitivity in detecting and
      localizing regional lymph node metastasis in bladder cancer.

PMID- 26294220
TI  - The estimated incidence of induced abortion in Kenya: a cross-sectional study.
AB  - BACKGROUND: The recently promulgated 2010 constitution of Kenya permits abortion
      when the life or health of the woman is in danger. Yet broad uncertainty remains
      about the interpretation of the law. Unsafe abortion remains a leading cause of
      maternal morbidity and mortality in Kenya. The current study aimed to determine
      the incidence of induced abortion in Kenya in 2012. METHODS: The incidence of
      induced abortion in Kenya in 2012 was estimated using the Abortion Incidence
      Complications Methodology (AICM) along with the Prospective Morbidity Survey
      (PMS). Data were collected through three surveys, (i) Health Facilities Survey
      (HFS), (ii) Prospective Morbidity Survey (PMS), and (iii) Health Professionals
      Survey (HPS). A total of 328 facilities participated in the HFS, 326 participated
      in the PMS, and 124 key informants participated in the HPS. Abortion numbers,
      rates, ratios and unintended pregnancy rates were calculated for Kenya as a whole
      and for five geographical regions. RESULTS: In 2012, an estimated 464,000 induced
      abortions occurred in Kenya. This translates into an abortion rate of 48 per
      1,000 women aged 15-49, and an abortion ratio of 30 per 100 live births. About
      120,000 women received care for complications of induced abortion in health
      facilities. About half (49%) of all pregnancies in Kenya were unintended and 41%
      of unintended pregnancies ended in an abortion. CONCLUSION: This study provides
      the first nationally-representative estimates of the incidence of induced
      abortion in Kenya. An urgent need exists for improving facilities' capacity to
      provide safe abortion care to the fullest extent of the law. All efforts should
      be made to address underlying factors to reduce risk of unsafe abortion.

PMID- 26294222
TI  - Atomic-scale luminescence measurement and theoretical analysis unveiling electron
      energy dissipation at a p-type GaAs(110) surface.
AB  - Luminescence of p-type GaAs was induced by electron injection from the tip of a
      scanning tunnelling microscope into a GaAs(110) surface. Atomically-resolved
      photon maps revealed a significant reduction in luminescence intensity at surface
      electronic states localized near Ga atoms. Theoretical analysis based on first
      principles calculations and a rate equation approach was performed to describe
      the perspective of electron energy dissipation at the surface. Our study reveals
      that non-radiative recombination through the surface states (SS) is a dominant
      process for the electron energy dissipation at the surface, which is suggestive
      of the fast scattering of injected electrons into the SS. 

PMID- 26294221
TI  - Open partial horizontal laryngectomy for salvage after failure of CO2 laser
      assisted surgery for glottic carcinoma.
AB  - Total laryngectomy (TL) is often still recommended as a salvage approach for
      recurrent laryngeal squamous cell carcinoma (LSCC). Considering LSCC recurrences
      after the failure of primary transoral laser microsurgery (TLM), open partial
      horizontal laryngectomy (OPHL) could be a valid alternative to TL in selected
      patients. The aim of the present study was to analyze retrospectively the
      oncological outcome of a consecutive series of 17 patients treated at the
      Otolaryngology Unit of Vittorio Veneto Hospital (Italy) with OPHL after primary
      TLM had failed. Nine patients (53 %) had no further recurrences after salvage
      OPHL. Eight patients had a second recurrence of LSCC after OPHL, and five of them
      were cured by further salvage treatment, while the other three died of their
      disease. We found an overall and disease-specific survival both of 82 % and a
      loco-regional control rate and an ultimate organ preservation rate of 82 and 70
      %, respectively. Patients who underwent two-stage bilateral cordectomy for
      primary glottic carcinoma showed a trend towards a higher rate of second
      recurrences, a lower ultimate organ preservation rate and a shorter disease-free
      survival after salvage OPHL. Further studies on larger cohorts of patients are
      needed to identify potential clinical and/or pathological prognostic parameters
      capable of pinpointing patients at higher risk of second recurrences after
      salvage OPHL in cases where TLM has failed. A salvage TL might be reasonably
      proposed as a first salvage choice in such cases.

PMID- 26294223
TI  - How close are we to revealing the etiology of Parkinson's disease?

PMID- 26294224
TI  - Signalling Events and Associated Pathways Related to the Mammalian Sperm
      Capacitation.
AB  - Capacitation is a biological phenomenon occurring prior to fertilization and is a
      multiple event process. Many physiological and biochemical changes takes place
      during the process; these changes are related to lipid composition of membrane,
      intracellular modulation of ion concentration, protein phosphorylation, sperm
      movement and membrane permeability. These events occur when the sperm is exposed
      to the new environment of ion concentration in the female reproductive tract.
      Ions such as bicarbonate and calcium facilitate capacitation by activating
      adenylyl cyclase, thus initiating protein kinase A (PKA) signalling cascade.
      Extracellular-regulated kinase pathway is activated by ligand binding to the
      membrane receptors and intracellular activation by reactive oxygen species (ROS).
      Activation of these pathways leads to the phosphorylation of different proteins,
      which is associated with events such as capacitation, hyperactivation and
      acrosome reaction that are essential for successful fertilization. Extensive
      studies were carried out on protein phosphorylation in relation to capacitation,
      but its role still remains ambiguous. 

PMID- 26294225
TI  - Antiviral Strategies Based on Lethal Mutagenesis and Error Threshold.
AB  - The concept of error threshold derived from quasispecies theory is at the basis
      of lethal mutagenesis, a new antiviral strategy based on the increase of virus
      mutation rate above an extinction threshold. Research on this strategy is
      justified by several inhibitor-escape routes that viruses utilize to ensure their
      survival. Successive steps in the transition from an organized viral quasispecies
      into loss of biologically meaningful genomic sequences are dissected. The
      possible connections between theoretical models and experimental observations on
      lethal mutagenesis are reviewed. The possibility of using combination of virus
      specific mutagenic nucleotide analogues and broad-spectrum, non-mutagenic
      inhibitors is evaluated. We emphasize the power that quasispecies theory has had
      to stimulate exploration of new means to combat pathogenic viruses. 

PMID- 26294226
TI  - Climate change on the Tibetan Plateau in response to shifting atmospheric
      circulation since the LGM.
AB  - The Tibetan Plateau (TP) is primarily influenced by the northern hemispheric
      middle latitude Westerlies and the Indian summer monsoon (ISM). The extent, long
      distance effects and potential long-term changes of these two atmospheric
      circulations are not yet fully understood. Here, we analyse modern airborne
      pollen in a transition zone of seasonally alternating dominance of the Westerlies
      and the ISM to develop a pollen discrimination index (PDI) that allows us to
      distinguish between the intensities of the two circulation systems. This index is
      applied to interpret a continuous lacustrine sedimentary record from Lake Nam Co
      covering the past 24 cal kyr BP to investigate long-term variations in the
      atmospheric circulation systems. Climatic variations on the central TP widely
      correspond to those of the North Atlantic (NA) realm, but are controlled through
      different mechanisms resulting from the changing climatic conditions since the
      Last Glacial Maximum (LGM). During the LGM, until 16.5 cal kyr BP, the TP was
      dominated by the Westerlies. After 16.5 cal kyr BP, the climatic conditions were
      mainly controlled by the ISM. From 11.6 to 9 cal kyr BP, the TP was exposed to
      enhanced solar radiation at the low latitudes, resulting in greater water
      availability. 

PMID- 26294227
TI  - Naloxone access increases, as does price.

PMID- 26294229
TI  - Alirocumab approved to help lower LDL cholesterol.

PMID- 26294230
TI  - Pharmacy technician's vigilance spurs drug recall.

PMID- 26294231
TI  - Summaries of Safety Labeling Changes Approved By FDA-Boxed Warnings Highlights
      April-June 2015.

PMID- 26294232
TI  - ASHP Past President Thomas J. Garrison dies at 75.

PMID- 26294233
TI  - Correction.

PMID- 26294234
TI  - Involving pharmacy students in writing a pharmacy newsletter.

PMID- 26294235
TI  - New pharmacy accreditation program.

PMID- 26294236
TI  - ASHP Foundation's Visiting Leaders Program.

PMID- 26294237
TI  - Simeprevir and sofosbuvir for treatment of hepatitis C infection.
AB  - PURPOSE: The pharmacology, pharmacokinetics, efficacy, safety, costs, and place
      in therapy of simeprevir and sofosbuvir in the management of hepatitis C virus
      (HCV) infection are reviewed. SUMMARY: Sofosbuvir and simeprevir are classified
      as direct-acting agents because they target specific proteins essential to the
      replication of HCV. Phase III trials demonstrated that simeprevir in combination
      with peginterferon alfa and ribavirin was superior to placebo combined with
      peginterferon alfa and ribavirin in achieving a sustained virological response in
      both treatment-naive patients and patients who relapsed after treatment with
      peginterferon alfa-2a or alfa-2b and ribavirin. Q80K polymorphism substantially
      decreases the efficacy of simeprevir. Clinical trials revealed that sofosbuvir in
      combination with ribavirin was superior to peginterferon plus ribavirin against
      HCV genotype 2 infection and as effective as peginterferon plus ribavirin against
      HCV genotype 3 infection. These findings were significant because they
      demonstrated the effectiveness of an anti-HCV regimen that did not include
      peginterferon alfa. Sofosbuvir has much better adverse-effect and drug
      interaction profiles than previous hepatitis C antiviral agents. Both simeprevir
      and sofosbuvir are approved for the treatment of chronic hepatitis C in
      combination with other antiviral medications. Simeprevir has been approved
      specifically for patients infected with HCV genotype 1 with compensated liver
      disease (including cirrhosis) in combination with peginterferon alfa-2a or alfa
      2b and ribavirin. Sofosbuvir has shown efficacy in HCV genotypes 1-4. CONCLUSION:
      Simeprevir and sofasbuvir have advantages in response rates and convenient dosage
      forms and frequency compared with other HCV treatments; however, they are more
      expensive than previous HCV therapies.

PMID- 26294238
TI  - Role of anaplastic lymphoma kinase inhibition in the treatment of non-small-cell
      lung cancer.
AB  - PURPOSE: Published data on the clinical efficacy, safety, dosage and
      administration, and costs of the anaplastic lymphoma kinase (ALK) inhibitors
      crizotinib and ceritinib in the treatment of non-small-cell lung cancer (NSCLC)
      are reviewed and compared. SUMMARY: The ALK protein functions as a transmembrane
      receptor tyrosine kinase; rearrangements of the ALK gene are associated with the
      development of NSCLC with adenocarcinoma histology. Crizotinib is an oral
      tyrosine kinase inhibitor approved in 2011 as a first-line therapy for patients
      with metastatic ALK mutation-driven NSCLC. Significantly improved response rates
      and progression-free survival (PFS) have been reported with the use of crizotinib
      therapy versus standard chemotherapy, but mutations conferring resistance to
      treatment develop in most cases. The second-generation ALK inhibitor ceritinib
      was approved in 2014 for the treatment of ALK-mutated NSCLC in patients who are
      intolerant or develop resistance to crizotinib. In a clinical trial of ceritinib
      involving 130 patients with ALK-positive NSCLC, the majority of whom had
      experienced disease progression during crizotinib use, patients receiving at
      least 400 mg of ceritinib daily had an overall response rate of 56% and median
      PFS of seven months. Adverse effects commonly reported with the use of either
      drug include visual disturbances, gastrointestinal disorders (e.g., diarrhea),
      and liver enzyme abnormalities. CONCLUSION: The tyrosine kinase inhibitors
      crizotinib and ceritinib provide an effective treatment approach for patients
      with ALK-mutated NSCLC. Efficacy data for both crizotinib and ceritinib indicate
      improved response rates and PFS with the use of either drug as an alternative to
      standard chemotherapy.

PMID- 26294239
TI  - Outcomes of pharmacist-assisted management of antiretroviral therapy in patients
      with HIV infection: A risk-adjusted analysis.
AB  - PURPOSE: The impact of pharmacist-assisted management (PAM) of pharmacotherapy
      for patients with human immunodeficiency virus (HIV) infection was investigated.
      METHODS: A retrospective cohort analysis was conducted to evaluate antiretroviral
      therapy (ART) outcomes in treatment-naive patients initiated on ART at an HIV
      clinic. Eligible patients enrolled in the clinic during the period 1999-2013 were
      classified into two groups: those referred to a clinic-based HIV pharmacist for
      initiation of ART (the PAM group) and those managed by a primary care provider
      (the control group). The primary study objective was the median time to viral
      suppression; secondary objectives included the durability of response to the
      first ART regimen. Relative hazards for the events of interest were estimated
      using a marginal structural Cox proportional hazards model and Kaplan-Meier
      curves, with inverse probability weights used to control for selection and
      confounding bias. RESULTS: Patients referred for PAM services (n = 819) typically
      had higher baseline viral loads and lower CD4+ cell counts than those in the
      control group (n = 436). The likelihood of viral suppression during the first two
      years after ART initiation was significantly higher in the PAM group versus the
      control group (hazard ratio, 1.37; 95% confidence interval, 1.18-1.59; p <
      0.0001). The median durability of the first ART regimen was 100 months in the PAM
      group versus 44 months in the control group (p > 0.05). CONCLUSION: In treatment
      naive patients, suppression of HIV viral load occurred earlier when pharmacists
      assisted with initiating ART than when ART was initiated without that assistance.

PMID- 26294240
TI  - Frequency of and risk factors for medication errors by pharmacists during order
      verification in a tertiary care medical center.
AB  - PURPOSE: The frequency of and risk factors for medication errors by pharmacists
      during order verification in a tertiary care medical center were reviewed.
      METHODS: This retrospective, secondary database study was conducted at a large
      tertiary care medical center in Houston, Texas. Inpatient and outpatient
      medication orders and medication errors recorded between July 1, 2011, and June
      30, 2012, were reviewed. Independent variables assessed as risk factors for
      medication errors included workload (mean number of orders verified per
      pharmacist per shift), work environment (type of day, type of shift, and mean
      number of pharmacists per shift), and nonmodifiable characteristics of the
      pharmacist (type of pharmacy degree obtained, age, number of years practicing,
      and number of years at the institution). RESULTS: A total of 1,887,751 medication
      orders, 92 medication error events, and 50 pharmacists were included in the
      study. The overall error rate was 4.87 errors per 100,000 verified orders. An
      increasing medication error rate was associated with an increased number of
      orders verified per pharmacist (p = 0.007), the type of shift (p = 0.021), the
      type of day (p = 0.002), and the mean number of pharmacists per shift (p =
      0.001). Pharmacist demographic variables were not associated with risk of error.
      The number of orders per shift was identified as a significant independent risk
      factor for medication errors (p = 0.019). CONCLUSION: An increase in the number
      of orders verified per shift was associated with an increased rate of pharmacist
      errors during order verification in a tertiary care medical center.

PMID- 26294241
TI  - Pharmacy residents' preparedness for the emotional challenges of patient care.
AB  - PURPOSE: Results of a survey to determine levels of pharmacy resident exposure to
      and preparedness for emotionally unsettling clinical scenarios are presented.
      METHODS: A pretested electronic survey was distributed to 1501 U.S. pharmacy
      residency program directors (RPDs), who were asked to complete the survey and
      forward it to residents in their programs. Both respondent groups provided
      perspectives on pharmacy residents' frequency of exposure to and preparedness for
      nine scenarios that could potentially be emotionally unsettling to pharmacy
      residents (e.g., a patient's death, participation in a response to a
      cardiorespiratory arrest). RPDs and residents were queried regarding training
      methods used by their programs to prepare trainees to cope with emotionally
      unsettling events. RESULTS: A total of 940 responses were received. Overall,
      resident-reported ex posure to the nine scenarios listed in the survey was
      infrequent. Majorities of both RPDs and residents (85.2% and 67.1%, respectively)
      indicated that residents could be better prepared for the emotional challenges of
      patient care. The most common method of training was a one-on-one discussion
      between a preceptor and a resident on an as-needed basis. No training was
      reported by 30% and 40% of RPDs and residents, respectively. CONCLUSION: The
      majority of RPD and resident respondents indicated that residents could be better
      prepared for the emotional challenges of patient care. The most commonly reported
      method of training for coping with emotional challenges was a one-on-one
      discussion between a preceptor and a resident on an as-needed basis.

PMID- 26294242
TI  - Implementation of a custom alert to prevent medication-timing errors associated
      with computerized prescriber order entry.
AB  - PURPOSE: The implementation of a custom alert to prevent medication-timing errors
      associated with the use of a computerized prescriber order-entry (CPOE) system is
      described. METHODS: In early 2013, Virginia Mason Medical Center began work to
      modify the CPOE system to make it impossible for a medication-timing error to
      occur. A visual control, a custom alert that forced prescribers to "self-inspect
      with pause" (a soft-stop override) before signing an order that may result in a
      medication-timing error, was developed. The prescriber could choose to modify the
      order to skip the next dose or change the start date or time of the order, cancel
      the order, or continue without altering the order. The custom alert was designed
      to fire only for medications that are administered once or twice daily. The
      effectiveness of the intervention was evaluated with interrupted time series
      before-and-after analysis of medication-timing errors. Outcomes measured included
      the proportion of errors that were corrected by the prescriber before signing the
      order and the number of medication-timing errors that reached patients. RESULTS:
      The proportion of orders where a prescriber modified the order as a result of the
      alert increased from 12% before the intervention to 29% postintervention (p >
      0.001), and this percentage continued to increase at five months postintervention
      (p < 0.001). The percentage of medication-timing errors that reached the patient
      decreased by 50% in the postintervention period. CONCLUSION: Medication-timing
      errors associated with the use of a CPOE system were corrected through
      implementation of a customized alert.

PMID- 26294243
TI  - Development of a metrics dashboard for monitoring involvement in the 340B Drug
      Pricing Program.
AB  - PURPOSE: An electronic tool to support hospital organizations in monitoring and
      addressing financial and compliance challenges related to participation in the
      340B Drug Pricing Program is described. SUMMARY: In recent years there has been
      heightened congressional and regulatory scrutiny of the federal 340B program,
      which provides discounted drug prices on Medicaid-covered drugs to safety net
      hospitals and other 340B-eligible healthcare organizations, or "covered
      entities." Historically, the 340B program has lacked a metrics-driven reporting
      framework to help covered entities capture the value of 340B program involvement,
      community benefits provided to underserved populations, and costs associated with
      compliance with 340B eligibility requirements. As part of an initiative by a
      large health system to optimize its 340B program utilization and regulatory
      compliance efforts, a team of pharmacists led the development of an electronic
      dashboard tool to help monitor 340B program activities at the system's 340B
      eligible facilities. After soliciting input from an array of internal and
      external 340B program stakeholders, the team designed the dashboard and
      associated data-entry tools to facilitate the capture and analysis of 340B
      program-related data in four domains: cost savings and revenue, program
      maintenance costs, community benefits, and compliance. CONCLUSION: A large health
      system enhanced its ability to evaluate and monitor 340B program-related
      activities through the use of a dashboard tool capturing key metrics on cost
      savings achieved, maintenance costs, and other aspects of program involvement.

PMID- 26294244
TI  - A cup of cool water.

PMID- 26294245
TI  - ASHP Guidelines on the Design of Database-Driven Clinical Decision Support:
      Strategic Directions for Drug Database and Electronic Health Records Vendors.

PMID- 26294248
TI  - A possible new paradigm? A survey-based assessment of the use of thawed group A
      plasma for trauma resuscitation in the United States.
AB  - BACKGROUND: Although evidence supporting this practice is limited, some centers
      use thawed group A plasma for the initial resuscitation of trauma patients. STUDY
      DESIGN AND METHODS: To better understand the current use of plasma in trauma
      resuscitation, a survey was developed, validated, and distributed via e-mail to
      121 American trauma centers. RESULTS: A total of 61 responses were received. Most
      were from Level 1 trauma centers (56/61, 92%) in urban settings (47/61, 77%).
      Virtually all centers reported maintaining A thawed plasma inventory (59/61,
      97%). Among the 56 Level 1 trauma center respondents, most keep thawed A
      immediately available (49/56, 88%) and many use group A plasma for trauma
      recipients of unknown ABO group (34/49, 69%). Half of the surveyed centers
      implemented this practice within the past year. The majority do not limit the
      amount of A plasma that can be administered to a patients of unknown ABO group
      (21/34, 62%), and most do not titer for anti-B (27/34, 79%). CONCLUSION: The
      majority of Level 1 trauma centers maintain thawed plasma inventories and use
      group A plasma for trauma recipients of unknown ABO group. Most centers do not
      limit the amount of group A plasma used in this situation or titer the anti-B.

PMID- 26294249
TI  - Response to the comments on "Human health risk assessment of pharmaceuticals and
      personal care products in plant tissue due to biosolids and manure amendments,
      and wastewater irrigation".

PMID- 26294250
TI  - Myth busting? Effects of embryo positioning and egg turning on hatching success
      in the water snake Natrix maura.
AB  - It is a common belief that reptile eggs should not be turned after oviposition
      once the embryo has attached itself to the inner membrane of the shell as it
      might kill developing embryos. Here, we used 338 eggs from 32 clutches of the
      water snake Natrix maura to (1) thoroughly describe natural clutch arrangement,
      (2) experimentally assess the effects of natural embryo positioning and (3) egg
      turning on embryo metabolism, hatching success, and hatchling phenotype. Clutches
      contained, on average, 59% of embryos located at the top, 28% at the bottom, and
      14% on a side of the egg. Larger females laid larger clutches with higher
      proportion of top located embryos. Top embryos displayed higher metabolic rates
      (heart rates), shorter incubation time, and produced lighter and shorter snakes
      than bottom embryos. Egg turning did not significantly influence egg development,
      hatching success or hatchling phenotypes. However, post-birth mortality was
      significantly higher in turned (37.5%) compared to unturned (4.5%) embryos,
      providing support to the common belief that eggs should not be moved from their
      natural position. 

PMID- 26294251
TI  - Reductions in aggression and violence following cognitive behavioural anger
      treatment for detained patients with intellectual disabilities.
AB  - BACKGROUND: Aggression is a significant problem amongst people with intellectual
      disabilities (ID), particularly those residing in hospital settings. Anger is
      related to aggression in secure services working people with ID, and the
      effectiveness of psychological interventions in reducing anger has been
      demonstrated in this population. However, no studies have systematically examined
      whether levels of aggression reduce following anger treatment with people with ID
      detained in secure settings. METHOD: This programme evaluation study concerns
      individually delivered cognitive anger treatment delivered to 50 patients (44 men
      and 6 women) with mild to borderline ID, delivered twice weekly for 18 sessions
      in a specialist forensic hospital service. Aggressive incidents and physical
      assault data were obtained from records 12 months pre-treatment and 12 months
      post-treatment. RESULTS: Following completion of treatment, the total number of
      aggressive incidents recorded in patients' files fell by 34.5%, and the post
      treatment reduction in the number of physical assaults was 55.9%. Analysis of the
      data partitioned into 6-month blocks over the 24-month study period showed that
      significant reductions in aggressive and violent incidents occurred in the
      assessment intervals following anger treatment. CONCLUSIONS: These findings
      reinforce the efficacy of cognitive behavioural anger treatment for detained
      patients with ID and histories of aggression; and despite its methodical
      limitations the study indicates the ecological validity of this treatment
      approach.

PMID- 26294252
TI  - Point mutation impairs centromeric CENH3 loading and induces haploid plants.
AB  - The chromosomal position of the centromere-specific histone H3 variant CENH3
      (also called "CENP-A") is the assembly site for the kinetochore complex of active
      centromeres. Any error in transcription, translation, modification, or
      incorporation can affect the ability to assemble intact CENH3 chromatin and can
      cause centromere inactivation [Allshire RC, Karpen GH (2008) Nat Rev Genet 9
      (12):923-937]. Here we show that a single-point amino acid exchange in the
      centromere-targeting domain of CENH3 leads to reduced centromere loading of CENH3
      in barley, sugar beet, and Arabidopsis thaliana. Haploids were obtained after
      cenh3 L130F-complemented cenh3-null mutant plants were crossed with wild-type A.
      thaliana. In contrast, in a noncompeting situation (i.e., centromeres possessing
      only mutated or only wild-type CENH3), no uniparental chromosome elimination
      occurs during early embryogenesis. The high degree of evolutionary conservation
      of the identified mutation site offers promising opportunities for application in
      a wide range of crop species in which haploid technology is of interest. 

PMID- 26294253
TI  - Geometrically controlled snapping transitions in shells with curved creases.
AB  - Curvature and mechanics are intimately connected for thin materials, and this
      coupling between geometry and physical properties is readily seen in folded
      structures from intestinal villi and pollen grains to wrinkled membranes and
      programmable metamaterials. While the well-known rules and mechanisms behind
      folding a flat surface have been used to create deployable structures and shape
      transformable materials, folding of curved shells is still not fundamentally
      understood. Shells naturally deform by simultaneously bending and stretching, and
      while this coupling gives them great stability for engineering applications, it
      makes folding a surface of arbitrary curvature a nontrivial task. Here we discuss
      the geometry of folding a creased shell, and demonstrate theoretically the
      conditions under which it may fold smoothly. When these conditions are violated
      we show, using experiments and simulations, that shells undergo rapid snapping
      motion to fold from one stable configuration to another. Although material
      asymmetry is a proven mechanism for creating this bifurcation of stability, for
      the case of a creased shell, the inherent geometry itself serves as a barrier to
      folding. We discuss here how two fundamental geometric concepts, creases and
      curvature, combine to allow rapid transitions from one stable state to another.
      Independent of material system and length scale, the design rule that we
      introduce here explains how to generate snapping transitions in arbitrary
      surfaces, thus facilitating the creation of programmable multistable materials
      with fast actuation capabilities. 

PMID- 26294255
TI  - Polo-like kinase and its inhibitors: Ready for the match to start?
AB  - Polo-like kinases (Plks) plays a central role in the normal cell cycle and their
      upregulation has been shown to play a role in the pathogenesis of multiple human
      cancers. Preclinical work demonstrates that targeting Plk has a significant
      impact on the treatment of both solid and hematologic malignancies in vitro and
      in vivo. We review here the basic science and clinical work to date with the Plks
      as well as future directions with this novel class of mitotic inhibitors.

PMID- 26294254
TI  - Velocities of unloaded muscle filaments are not limited by drag forces imposed by
      myosin cross-bridges.
AB  - It is not known which kinetic step in the acto-myosin ATPase cycle limits
      contraction speed in unloaded muscles (V0). Huxley's 1957 model [Huxley AF (1957)
      Prog Biophys Biophys Chem 7:255-318] predicts that V0 is limited by the rate that
      myosin detaches from actin. However, this does not explain why, as observed by
      Barany [Barany M (1967) J Gen Physiol 50(6, Suppl):197-218], V0 is linearly
      correlated with the maximal actin-activated ATPase rate (vmax), which is limited
      by the rate that myosin attaches strongly to actin. We have observed smooth
      muscle myosin filaments of different length and head number (N) moving over
      surface-attached F-actin in vitro. Fitting filament velocities (V) vs. N to a
      detachment-limited model using the myosin step size d=8 nm gave an ADP release
      rate 8.5-fold faster and ton (myosin's attached time) and r (duty ratio) ~10-fold
      lower than previously reported. In contrast, these data were accurately fit to an
      attachment-limited model, V=N.v.d, over the range of N found in all muscle types.
      At nonphysiologically high N, V=L/ton rather than d/ton, where L is related to
      the length of myosin's subfragment 2. The attachment-limited model also fit well
      to the [ATP] dependence of V for myosin-rod cofilaments at three fixed N.
      Previously published V0 vs. vmax values for 24 different muscles were accurately
      fit to the attachment-limited model using widely accepted values for r and N,
      giving d=11.1 nm. Therefore, in contrast with Huxley's model, we conclude that V0
      is limited by the actin-myosin attachment rate.

PMID- 26294256
TI  - Getting Off on the Right Foot: The Many Roles of the Psychosocial Evaluation in
      the Bariatric Surgery Practice.
AB  - A thorough and specialized pre-operative psychosocial assessment is an important
      part of a comprehensive bariatric treatment protocol. Over time, the presurgical
      psychosocial evaluation has evolved from a cut-and-dried process of recommending
      whether a patient should or should not undergo surgery to a more nuanced and
      multifaceted process that serves multiple functions. In this article, we review
      the many ways in which the pre-operative psychosocial evaluation can enhance
      patient outcomes and adjustment and even the functioning of the interdisciplinary
      bariatric surgery team.

PMID- 26294257
TI  - Morus nigra leaf extract improves glycemic response and redox profile in the
      liver of diabetic rats.
AB  - Diabetes mellitus (DM) is a chronic metabolic disorder characterized by
      hyperglycemia and alterations in the carbohydrate, lipid, and protein metabolism.
      DM is associated with increased oxidative stress and pancreatic beta cell damage,
      which impair the production of insulin and the maintenance of normoglycemia.
      Inhibiting oxidative damage and controlling hyperglycemia are two important
      strategies for the prevention of diabetes. The pulp and leaf extracts of mulberry
      (Morus nigra L.) have abundant total phenolics and flavonoids, and its
      antioxidant potential may be an important factor for modulating oxidative stress
      induced by diabetes. In this study, DM was induced by intraperitoneal injection
      of alloxan monohydrate (135 mg kg(-1)). Female Fischer rats were divided into
      four groups: control, diabetic, diabetic pulp, and diabetic leaf extract. Animals
      in the diabetic pulp and diabetic leaf extract groups were treated for 30 days
      with M. nigra L. pulp or leaf extracts, respectively. At the end of treatment,
      animals were euthanized and, liver and blood samples were collected for analysis
      of biochemical and metabolic parameters. Our study demonstrated that treatment of
      diabetic rats with leaf extracts decreased the superoxide dismutase
      (SOD)/catalase (CAT) ratio and carbonylated protein levels by reducing oxidative
      stress. Moreover, the leaf extract of M. nigra L. decreased the matrix
      metalloproteinase (MMP)-2 activity, increased insulinemia, and alleviated
      hyperglycemia-induced diabetes. In conclusion, our study found that the leaf
      extract of M. nigra L. improved oxidative stress and complications in diabetic
      rats, suggesting the utility of this herbal remedy in the prevention and
      treatment of DM. 

PMID- 26294259
TI  - In Response to Letter to the Editor: Torsney KM, Cocker DM, Slesser AAP (2015)
      The Modern Surgeon and Competency Assessment: Are the Workplace-Based Assessments
      Evidence-Based?

PMID- 26294260
TI  - Species differences in metabolism of EPZ015666, an oxetane-containing protein
      arginine methyltransferase-5 (PRMT5) inhibitor.
AB  - 1. Metabolite profiling and identification studies were conducted to understand
      the cross-species differences in the metabolic clearance of EPZ015666, a first-in
      class protein arginine methyltransferase-5 (PRMT5) inhibitor, with anti
      proliferative effects in preclinical models of Mantle Cell Lymphoma. EPZ015666
      exhibited low clearance in human, mouse and rat liver microsomes, in part by
      introduction of a 3-substituted oxetane ring on the molecule. In contrast, a
      higher clearance was observed in dog liver microsomes (DLM) that translated to a
      higher in vivo clearance in dog compared with rodent. 2. Structure elucidation
      via high resolution, accurate mass LC-MS(n) revealed that the prominent
      metabolites of EPZ015666 were present in hepatocytes from all species, with the
      highest turnover rate in dogs. M1 and M2 resulted from oxidative oxetane ring
      scission, whereas M3 resulted from loss of the oxetane ring via an N-dealkylation
      reaction. 3. The formation of M1 and M2 in DLM was significantly abrogated in the
      presence of the specific CYP2D inhibitor, quinidine, and to a lesser extent by
      the CYP3A inhibitor, ketoconazole, corroborating data from human recombinant
      isozymes. 4. Our data indicate a marked species difference in the metabolism of
      the PRMT5 inhibitor EPZ015666, with oxetane ring scission the predominant
      metabolic pathway in dog mediated largely by CYP2D.

PMID- 26294258
TI  - Metabolomic analysis of exercise effects in the POLG mitochondrial DNA mutator
      mouse brain.
AB  - Mitochondrial DNA (mtDNA) mutator mice express a mutated form of mtDNA polymerase
      gamma that results an accelerated accumulation of somatic mtDNA mutations in
      association with a premature aging phenotype. An exploratory metabolomic analysis
      of cortical metabolites in sedentary and exercised mtDNA mutator mice and wild
      type littermate controls at 9-10 months of age was performed. Pathway analysis
      revealed deficits in the neurotransmitters acetylcholine, glutamate, and
      aspartate that were ameliorated by exercise. Nicotinamide adenine dinucleotide
      (NAD) depletion and evidence of increased poly(adenosine diphosphate-ribose)
      polymerase 1 (PARP1)activity were apparent in sedentary mtDNA mutator mouse
      cortex, along with deficits in carnitine metabolites and an upregulated
      antioxidant response that largely normalized with exercise. These data highlight
      specific pathways that are altered in the brain in association with an
      accelerated age-related accumulation of somatic mtDNA mutations. These results
      may have relevance to age-related neurodegenerative diseases associated with
      mitochondrial dysfunction, such as Alzheimer's disease and Parkinson's disease
      and provide insights into potential mechanisms of beneficial effects of exercise
      on brain function. 

PMID- 26294262
TI  - Complementary Flavonoid Prenylations by Fungal Indole Prenyltransferases.
AB  - Flavonoids are found mainly in plants and exhibit diverse biological and
      pharmacological activities, which can often be enhanced by prenylations. In
      plants, such reactions are catalyzed by membrane-bound prenyltransferases. In
      this study, the prenylation of nine flavonoids from different classes by a
      soluble fungal prenyltransferase (AnaPT) involved in the biosynthesis of the
      prenylated indole alkaloid acetylaszonalenin is demonstrated. The behavior of
      AnaPT toward flavonoids regarding substrate acceptance and prenylation positions
      clearly differs from that of the indole prenyltransferase 7-DMATS. The two
      enzymes are therefore complementary in flavonoid prenylations. 

PMID- 26294261
TI  - Dual antiplatelet therapy with clopidogrel and aspirin for secondary stroke
      prevention.
AB  - Stroke is a major public health concern worldwide, and 25 % of stroke victims
      would have another stroke. Although administration of antiplatelet agents has
      been confirmed to be one of the major approaches for secondary prevention of
      noncardioembolic stroke, the short-term or long-term use of aspirin plus
      clopidogrel for secondary stroke prevention remains to be controversial. This
      article aims at providing a comprehensive review of the evidence on the use of
      aspirin plus clopidogrel for secondary stroke prevention, with special focus on
      important studies that may impact clinical practice of treating patients with
      stroke or transient ischemic attack. 

PMID- 26294264
TI  - Regulatory watch: What drives differences in review times among CDER divisions?

PMID- 26294263
TI  - A new small molecule inhibits Streptococcus mutans biofilms in vitro and in vivo.
AB  - AIMS: The aim of this study was to identify new small molecules that can inhibit
      Streptococcus mutans biofilms by in vitro and in vivo model. METHODS AND RESULTS:
      We evaluated the effect of a small molecule 2-amino-imidazole/triazole conjugate
      (2-AI/T) on the formation of Strep. mutans biofilms by culturing in 96-well
      plates. Toxicity was assessed through cell culture and intragastrically
      administering to mice. The anti-biofilm and anti-caries effects were investigated
      in vivo. The inhibitive mechanism was detected by isobaric tag for relative and
      absolute quantification (itraq) and RT-QPCR. In vitro and in vivo study revealed
      that 2-AI/T significantly inhibited biofilm formation of Strep. mutans and is
      more so than inhibiting planktonic cells without toxicity. The ribosome and
      histidine metabolism pathways of Strep. mutans were significantly regulated by
      this compound. CONCLUSIONS: These results suggest that the 2-AI/T conjugate is a
      potent inhibitor that can be potentially developed into a new drug to treat and
      prevent dental caries. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first
      study to use small molecule from marine natural products, to protect from dental
      caries in vivo. It has potential broad range application in clinical caries
      prevention, or as a bioactive ingredient for food applications.

PMID- 26294265
TI  - Why is it hard to terminate failing projects in pharmaceutical R&D?
AB  - 'Quick-kill' strategies in pharmaceutical research and development aim to reduce
      late-stage attrition by bringing project termination decisions forward, to an
      earlier point in the process. How can the barriers to implementing such
      strategies be overcome? 

PMID- 26294266
TI  - Deal watch: Celgene bets big on Scripps-originated autoimmunity candidate.

PMID- 26294267
TI  - Operating Profitability of For-Profit and Not-for-Profit Florida Community
      Hospitals During Medicare Policy Changes, 2000 to 2010.
AB  - Medicare Advantage was implemented in 2004 and the Recovery Audit Contractor
      (RAC) program was implemented in Florida during 2005. Both increase surveillance
      of medical necessity and deny payments for improper admissions. The purpose of
      the present study was to determine their potential impact on for-profit (FP) and
      not-for-profit (NFP) hospital operating margins in Florida. FP hospitals were
      expected to be more adversely affected as admissions growth has been one strategy
      to improve stock performance, which is not a consideration at NFPs. This study
      analyzed Florida community hospitals from 2000 through 2010, assessing changes in
      pre-tax operating margin (PTOM). Florida Agency for Health Care Administration
      data were analyzed for 104 community hospitals (62 FPs and 42 NFPs). Academic,
      public, and small hospitals were excluded. A mixed-effects model was used to
      assess the association of RAC implementation, organizational and payer type
      variables, and ownership interaction effects on PTOM. FP hospitals began the
      period with a higher average PTOM, but converged with NFPs during the study
      period. The average Medicare Advantage effect was not significant for either
      ownership type. The magnitude of the RAC variable was significantly negative for
      average PTOM at FPs (-4.68) and positive at NFPs (0.08), meaning RAC was
      associated with decreasing PTOM at FP hospitals only. RAC complements other
      Medicare surveillance systems that detect medically unnecessary admissions,
      coding errors, fraud, and abuse. Since its implementation in Florida, average FP
      and NFP operating margins have been similar, such that the higher margins
      reported for FP hospitals in the 1990s are no longer evident. 

PMID- 26294268
TI  - Open-Loop Audio-Visual Stimulation (AVS): A Useful Tool for Management of
      Insomnia?
AB  - Audio Visual Stimulation (AVS), a form of neurofeedback, is a non-pharmacological
      intervention that has been used for both performance enhancement and symptom
      management. We review the history of AVS, its two sub-types (close- and open
      loop), and discuss its clinical implications. We also describe a promising new
      application of AVS to improve sleep, and potentially decrease pain. AVS research
      can be traced back to the late 1800s. AVS's efficacy has been demonstrated for
      both performance enhancement and symptom management. Although AVS is commonly
      used in clinical settings, there is limited literature evaluating clinical
      outcomes and mechanisms of action. One of the challenges to AVS research is the
      lack of standardized terms, which makes systematic review and literature
      consolidation difficult. Future studies using AVS as an intervention should; (1)
      use operational definitions that are consistent with the existing literature,
      such as AVS, Audio-visual Entrainment, or Light and Sound Stimulation, (2)
      provide a clear rationale for the chosen training frequency modality, (3) use a
      randomized controlled design, and (4) follow the Consolidated Standards of
      Reporting Trials and/or related guidelines when disseminating results.

PMID- 26294269
TI  - Neurofeedback in Learning Disabled Children: Visual versus Auditory
      Reinforcement.
AB  - Children with learning disabilities (LD) frequently have an EEG characterized by
      an excess of theta and a deficit of alpha activities. NFB using an auditory
      stimulus as reinforcer has proven to be a useful tool to treat LD children by
      positively reinforcing decreases of the theta/alpha ratio. The aim of the present
      study was to optimize the NFB procedure by comparing the efficacy of visual (with
      eyes open) versus auditory (with eyes closed) reinforcers. Twenty LD children
      with an abnormally high theta/alpha ratio were randomly assigned to the Auditory
      or the Visual group, where a 500 Hz tone or a visual stimulus (a white square),
      respectively, was used as a positive reinforcer when the value of the theta/alpha
      ratio was reduced. Both groups had signs consistent with EEG maturation, but only
      the Auditory Group showed behavioral/cognitive improvements. In conclusion, the
      auditory reinforcer was more efficacious in reducing the theta/alpha ratio, and
      it improved the cognitive abilities more than the visual reinforcer.

PMID- 26294270
TI  - Comparison of International Prognostic Index and NCCN-IPI in 324 patients with de
      novo diffuse large B-cell lymphoma: a multi-center retrospective analysis.

PMID- 26294271
TI  - Early warning signs for saddle-escape transitions in complex networks.
AB  - Many real world systems are at risk of undergoing critical transitions, leading
      to sudden qualitative and sometimes irreversible regime shifts. The development
      of early warning signals is recognized as a major challenge. Recent progress
      builds on a mathematical framework in which a real-world system is described by a
      low-dimensional equation system with a small number of key variables, where the
      critical transition often corresponds to a bifurcation. Here we show that in high
      dimensional systems, containing many variables, we frequently encounter an
      additional non-bifurcative saddle-type mechanism leading to critical transitions.
      This generic class of transitions has been missed in the search for early
      warnings up to now. In fact, the saddle-type mechanism also applies to low
      dimensional systems with saddle-dynamics. Near a saddle a system moves slowly and
      the state may be perceived as stable over substantial time periods. We develop an
      early warning sign for the saddle-type transition. We illustrate our results in
      two network models and epidemiological data. This work thus establishes a
      connection from critical transitions to networks and an early warning sign for a
      new type of critical transition. In complex models and big data we anticipate
      that saddle-transitions will be encountered frequently in the future. 

PMID- 26294272
TI  - [Security of hospital infusion practices: From an a priori risk analysis to an
      improvement action plan].
AB  - OBJECTIVES: Infusion in care units, and all the more in intensive care units, is
      a complex process which can be the source of many risks for the patient. Under
      cover of an institutional approach for the improvement of the quality and safety
      of patient healthcare, a risk mapping infusion practices was performed. METHODS:
      The analysis was focused on intravenous infusion situations in adults, the a
      priori risk assessment methodology was applied and a multidisciplinary work group
      established. RESULTS: Forty-three risks were identified for the infusion process
      (prescription, preparation and administration). The risks' assessment and the
      existing means of control showed that 48% of them would have a highly critical
      patient security impact. Recommendations were developed for 20 risks considered
      to be most critical, to limit their occurrence and severity, and improve their
      control level. An institutional action plan was developed and validated in the
      Drug and Sterile Medical Devices Commission. CONCLUSION: This mapping allowed the
      realization of an exhaustive inventory of potential risks associated with the
      infusion. At the end of this work, multidisciplinary groups were set up to work
      on different themes and regular quarterly meetings were established to follow the
      progress of various projects. Risk mapping will be performed in pediatric and
      oncology unit where the risks associated with the handling of toxic products is
      omnipresent.

PMID- 26294273
TI  - [Hospital pharmacists' perception of pharmacovigilance in Quebec].
AB  - OBJECTIVES: To assess the pharmacovigilance perception of Quebec's hospital
      pharmacists. METHODS: Cross-sectional study. A questionnaire with 16 questions
      was developed in order to assess respondents' perception of their ability to
      practice pharmacovigilance, factors that can influence adverse drug reactions
      reporting and measures to increase reporting rate. The online questionnaire was
      sent to hospital pharmacist from Quebec in April 2014. The results were presented
      in the form of descriptive data. RESULTS: A total of 179/252 (71%) hospital
      pharmacists responded. More than 90% of respondents considered that they were
      able to practice all activities related to pharmacovigilance. During one year of
      practice, 98% of respondents faced at least one serious or unexpected adverse
      drug reaction and 77% notified at least one adverse drug reaction to Health
      Canada. The factors encouraging more than 89% of respondents to notify were: the
      severity, the rapidity of onset, the visibility of the reaction, the fact that
      the adverse drug reaction was unexpected or due to a recent marketed drug. More
      than 69% of respondents considered the overwork as the principal obstacle to the
      notification. The majority of respondents supported the implementation of 13/14
      measures in order to increase reporting rate. CONCLUSION: Hospital pharmacists
      from Quebec presented a favorable ability to practice pharmacovigilance. Analysis
      of their perception of pharmacovigilance helped to identify improvements, such as
      the implementation of a pharmacovigilance coordinator in the health center.

PMID- 26294274
TI  - Filling the gap: Micro-C accesses the nucleosomal fiber at 100-1000 bp
      resolution.
AB  - The fine three-dimensional structure of the nucleosomal fiber has remained
      elusive to genome-wide chromosome conformation capture (3C) approaches. A new
      study mapping contacts at the single nucleosome level (Micro-C) reveals
      topological interacting domains along budding yeast chromosomes. These domains
      encompass one to five consecutive genes and are delimited by highly active
      promoters. 

PMID- 26294275
TI  - The Potential of High-throughput Metagenomic Sequencing of Aquatic Bacterial
      Communities to Estimate the Postmortem Submersion Interval.
AB  - Human remains can be discovered in freshwater or marine ecosystems, circumstances
      where insects and other invertebrates have infrequently been used for
      understanding the time of postmortem submersion. In this study, the
      identification and succession of epinecrotic bacterial communities on vertebrate
      remains were described during decomposition in a temperate headwater stream
      during two seasons (summer and winter). Bacterial communities were characterized
      with 454 pyrosequencing and analyzed at phyletic and generic taxonomic
      resolutions. There was a significant increase in genera richness over
      decomposition during both seasons. Additionally, multivariate statistical
      modeling revealed significant differences in bacterial communities between
      seasons at both taxonomic resolutions and siginificant genera differences among
      sampling days within each season, suggesting a succession of these communities.
      These data are the first to describe aquatic bacterial succession using high
      throughput metagenomic sequencing on vertebrate remains submerged in a freshwater
      habitat, and provide initial evidence for their potential use in forensic
      investigations.

PMID- 26294276
TI  - Practical Applications for Maintenance of Certification Products in Child and
      Adolescent Residency Training.
AB  - OBJECTIVE: The authors evaluated whether Maintenance of Certification (MOC)
      Performance-in-Practice products in training increases trainee knowledge of MOC
      processes and is viewed by trainees as a useful activity. METHODS: Six child and
      adolescent psychiatry fellowships used MOC products in continuity clinics to
      assess their usefulness as training tools. Two surveys assessed initial knowledge
      of MOC and usefulness of the activity. RESULTS: Forty-one fellows completed the
      initial survey. A majority of first-year fellows indicated lack of awareness of
      MOC in contrast to a majority of second-year fellows who indicated some
      awareness. Thirty-five fellows completed the second survey. A majority of first-
      and second-year fellows found the activity easy to execute and would change
      something about their practice as a result. CONCLUSIONS: Using MOC products in
      training appears to be a useful activity that may assist training programs in
      teaching the principles of self- and peer-learning.

PMID- 26294278
TI  - Comparison of significant single nucleotide polymorphisms selections in GWAS for
      complex traits.
AB  - The goal of this study was to compare significant SNP selection approaches in the
      context of complex traits based on SNP estimates obtained by models: a model
      fitting a single SNP (M1), a model fitting a single SNP and a random polygenic
      effect (M2), the nonparametric CAR score (M3), a SNP-BLUP model with random
      effects of all SNPs fitted simultaneously (M4). There were 46,267 SNPs tested in
      a population of 2601 Holstein Friesian bulls, four traits (milk and fat yields,
      somatic cell score, non-return rate for heifers) were considered. The numbers of
      SNPs selected as significant differed among models. M1 selected a very large
      number of SNPs, except for a NRH in which no SNPs were significant. M2 and M3
      both selected similar and low number of SNPs for each trait. M4 selected more
      SNPs than M2 and M3. Considering linkage disequilibrium between SNPs, for MY M2
      and M3 selected SNPs more highly correlated with each other than in the case of
      M4, while for FY M3 selection contained more correlated SNPs than M2 and M4. In
      conclusion, if the research interest is to identify SNPs not only with strong,
      but also with moderate effects on a complex trait a multiple-SNP model is
      recommended. Such models are capable of accounting for at least a part of linkage
      disequilibrium between SNPs through the design matrix of SNP effects. Functional
      annotation of SNPs significant in M4 reveals good correspondence between selected
      polymorphisms and functional information as well as with QTL mapping results.

PMID- 26294277
TI  - Genetic association and interaction between the IRF5 and TYK2 genes and systemic
      lupus erythematosus in the Han Chinese population.
AB  - OBJECTIVES: The purpose of this case-control study was to investigate whether
      polymorphisms and gene-gene interactions of the two type I interferon (IFN) genes
      (IRF5 and TYK2) are the susceptible factors of systemic Lupus erythematosus (SLE)
      in the Han Chinese population. METHODS: The four variants [rs2004640, rs2070197,
      rs10954213 and exon6 insertion/deletion (in/de)] of IRF5 gene and five single
      nucleotide polymorphisms (SNPs) (rs280500, rs280519, rs2304256, rs8108236,
      rs12720270) of TYK2 gene were examined in a cohort of 642 SLE patients and 642
      healthy controls. Genotyping was conducted using polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) and confirmed by direct
      sequencing in 10 % sample randomly. RESULTS: Rs2070197 was not polymorphic in
      this study, and was excluded in further analysis. Significant association was
      found for loci on IRF5 (rs2004640: p = 0.0003, p corr = 0.0012) and TYK2
      (rs280500: p = 8.83 * 10(-6), p corr = 4.41 * 10(-5); rs2304256: p = 3.71 * 10(
      6), p corr = 1.85 * 10(-5); rs8108236: p = 0.0004, p corr = 0.002), but not for
      other SNPs. Significant association was also observed for genotypes of IRF5
      (rs2004640, p = 0.0009, p corr = 0.0036) and TYK2 SNPs (rs280500: p = 5.21 * 10(
      5), p corr = 2.61 * 10(-4); rs2304256: p = 7.72 * 10(-6), p corr = 3.86 * 10(-5);
      rs8108236: p = 0.002, p corr = 0.01). Nevertheless, two haplotypes based on the 3
      variants [exon6(in/de), rs10954213, rs2004640] of IRF5 (DAG and IAT) could define
      protective or susceptibility haplotype in SLE. Similarly, three haplotypes
      containing 5 SNPs (rs280500, rs280519, rs2304256, rs8108236, rs12720270) of TYK2
      (GATAT, AGGAT and GAGGT) may also be associated with SLE in Han Chinese.
      Additionally, the gene-gene interaction analysis was conducted on the IRF5 and
      TYK2 SNPs. And a three-way interaction between TYK2 rs280500, rs2304256 and IRF5
      rs10954213 and SLE was found (p < 0.0001). CONCLUSIONS: Genetic associations and
      gene-gene interactions of IRF5 and TYK2 were significantly detected in Han
      Chinese with SLE. Our results had important implications for future research on
      the role of type I IFN function in SLE susceptibility.

PMID- 26294279
TI  - Molecular basis of hypohidrotic ectodermal dysplasia: an update.
AB  - Recent advances in understanding the molecular events underlying hypohidrotic
      ectodermal dysplasia (HED) caused by mutations of the genes encoding proteins of
      the tumor necrosis factor alpha (TNFalpha)-related signaling pathway have been
      presented. These proteins are involved in signal transduction from ectoderm to
      mesenchyme during development of the fetus and are indispensable for the
      differentiation of ectoderm-derived structures such as eccrine sweat glands,
      teeth, hair, skin, and/or nails. Novel data were reviewed and discussed on the
      structure and functions of the components of TNFalpha-related signaling pathway,
      the consequences of mutations of the genes encoding these proteins, and the
      prospect for further investigations, which might elucidate the origin of HED.

PMID- 26294281
TI  - The impact of hand reflexology on pain, anxiety and satisfaction during minimally
      invasive surgery under local anaesthetic: a randomised controlled trial.
AB  - BACKGROUND: Elevated patient anxiety during surgery is linked to a range of
      suboptimal treatment outcomes. Reflexology has been reported to be effective in
      reducing pre and post-operative anxiety and post-operative pain. OBJECTIVES: To
      explore whether the addition of hand reflexology to treatment as usual during
      minimally invasive varicose vein surgery under local anaesthetic impacted upon
      patient reported anxiety and pain during surgery, and patient satisfaction with
      treatment. DESIGN: Randomised controlled trial. SETTING: Private outpatient
      clinic specialising in venous conditions. PARTICIPANTS: 137 participants were
      assessed for eligibility. One hundred patients were recruited (mean age 47.8
      years, 83% female). Participants received endovenous thermal ablation and/or
      phlebectomy for the treatment of varicose veins. Inclusion criteria included age
      (between 18 and 80) and receiving endovenous thermal ablation and/or phlebectomy
      for the treatment of varicose veins under local anaesthetic. Exclusion criteria
      included the presence of leg ulcers and receiving microsclerotherapy or foam
      sclerotherapy treatments, being unwilling to enter into the randomisation process
      and arriving late at the clinic. METHODS: Participants were randomly allocated to
      either treatment as usual (control group) or intra-operative hand reflexology
      during minimally invasive varicose vein surgery under local anaesthetic.
      Participants in the reflexology group received a session of intra-operative hand
      reflexology which began in the operating theatre, prior to analgesic injections
      and continued until surgery was complete. It was not possible to blind the
      participants, researchers or theatre staff to group allocation due to the
      modifications required to the operating theatre for participants in the
      reflexology group. The researcher could not be blinded due to the role they
      played in the trial organisation. RESULTS: Of the 137 participants screened for
      eligibility, 7 participants declined to participate and a further 30 did not meet
      the inclusion criteria, giving a recruitment rate of 93%. Fifty participants were
      randomised to the reflexology group and fifty participants were randomised to the
      control group. Intra-operative anxiety was significantly lower in the reflexology
      group (mean score of 3.24 on an 11-point rating scale) than the control group
      (mean score of 5.0, p<.001). CONCLUSIONS: Intra-operative hand reflexology is a
      useful adjunct to local anaesthetic varicose vein surgery, with participants in
      the reflexology group reporting significantly lower intra-operative anxiety and
      shorter pain duration than participants receiving treatment as usual.

PMID- 26294280
TI  - Genetic control of bacterial biofilms.
AB  - Nearly all bacterial species, including pathogens, have the ability to form
      biofilms. Biofilms are defined as structured ecosystems in which microbes are
      attached to surfaces and embedded in a matrix composed of polysaccharides, eDNA,
      and proteins, and their development is a multistep process. Bacterial biofilms
      constitute a large medical problem due to their extremely high resistance to
      various types of therapeutics, including conventional antibiotics. Several
      environmental and genetic signals control every step of biofilm development and
      dispersal. From among the latter, quorum sensing, cyclic diguanosine-5'
      monophosphate, and small RNAs are considered as the main regulators. The present
      review describes the control role of these three regulators in the life cycles of
      biofilms built by Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella
      enterica serovar Typhimurium, and Vibrio cholerae. The interconnections between
      their activities are shown. Compounds and strategies which target the activity of
      these regulators, mainly quorum sensing inhibitors, and their potential role in
      therapy are also assessed.

PMID- 26294282
TI  - Translocation and dissemination to target neurons of botulinum neurotoxin type B
      in the mouse intestinal wall.
AB  - Botulinum neurotoxins (BoNTs) are responsible for severe flaccid paralysis
      (botulism), which in most cases enter the organism via the digestive tract and
      then disseminate into the blood or lymph circulation to target autonomic and
      motor nerve endings. The passage way of BoNTs alone or in complex forms with
      associated nontoxic proteins through the epithelial barrier of the digestive
      tract still remains unclear. Here, we show using an in vivo model of mouse
      ligated intestinal loop that BoNT/B alone or the BoNT/B C-terminal domain of the
      heavy chain (HCcB), which interacts with cell surface receptors, translocates
      across the intestinal barrier. The BoNT/B or HCcB translocation through the
      intestinal barrier occurred via an endocytosis-dependent mechanism within 10-20
      min, because Dynasore, a potent endocytosis inhibitor, significantly prevented
      BoNT/B as well as HCcB translocation. We also show that HCcB or BoNT/B
      specifically targets neuronal cells and neuronal extensions in the intestinal
      submucosa and musculosa expressing synaptotagmin, preferentially cholinergic
      neurons and to a lower extent other neuronal cell types, notably serotonergic
      neurons. Interestingly, rare intestinal epithelial cells accumulated HCcB
      suggesting that distinct cell types of the intestinal epithelium, still
      undefined, might mediate efficient translocation of BoNT/B. 

PMID- 26294283
TI  - Curcumin Increases HSP70 Expression in Primary Rat Cortical Neuronal Apoptosis
      Induced by gp120 V3 Loop Peptide.
AB  - Neuronal cell dysfunction and apoptosis are the main causes of the invasion of
      the central nervous system by human immunodeficiency virus type 1 (HIV-1),
      although the underlying mechanism has not been well understood. Recent research
      has shown that curcumin might play an important role in regulating HIV-1
      development. Heat shock protein 70 (HSP70), a protein induced by heat, was
      reported to inhibit apoptosis through various cell signaling pathways in brain.
      Overexpression of HSP70 could effectively protected neurons in many animal and
      cellular models of dementia. In the present study, the expression of HSP70 in the
      gp120 V3 loop peptide-induced neuronal apoptosis was investigated. Our results
      demonstrated that gp120 V3 loop peptide could induce primary rat cortical
      neuronal apoptosis. We also found that curcumin could increase HSP70 expression.
      In addition, the expression level of both HSP70 mRNA and HSP70 protein were
      dependent on the curcumin dose in the rat cortical neurons. Curcumin could
      improve HSP70 expression in gp120 V3 loop peptide-induced primary rat cortical
      neuronal apoptosis. In general, our results indicated that curcumin played an
      important role in the gp120 V3 loop peptide induced neuronal apoptosis by
      regulating HSP70. 

PMID- 26294285
TI  - A Ratiometric Luminescent Thermometer Co-doped with Lanthanide and Transition
      Metals.
AB  - Herein, we report the fabrication of a sensitive ratiometric and colorimetric
      luminescent thermometer with a wide operating-temperature range, from cryogenic
      temperatures up to high temperatures, through the combination of lanthanide and
      transition metal complexes. Benefiting from the transition metal complex as a
      self-reference, the lanthanide content in the mixed-coordination complex,
      Eu0.05(Mebip-mim bromine)0.15Zn0.95(Mebip-mim bromine)1.9, was lowered to 5%.

PMID- 26294284
TI  - Orthosteric, Allosteric and Biased Signalling at the Relaxin-3 Receptor RXFP3.
AB  - Relaxin-3 is a neuropeptide that has roles in stress, memory and appetite
      regulation. The peptide acts on its cognate receptor RXFP3 to induce coupling to
      inhibitory G proteins to inhibit adenylyl cyclase and activate MAP-kinases such
      as ERK1/2, p38MAPK and JNK. Other relaxin family peptides can activate the
      receptor to produce alternative patterns of signalling and there is an allosteric
      modulator 135PAM1 that displays probe-selectivity. There are now a variety of
      selective peptide agonists and antagonists that will assist in the determination
      of the physiological roles of the relaxin-RXFP3 system and its potential as a
      drug target. 

PMID- 26294286
TI  - Photocatalytic Properties of TiO2: Evidence of the Key Role of Surface Active
      Sites in Water Oxidation.
AB  - Photocatalytic activity of oxide semiconductors is commonly considered in terms
      of the effect of the band gap on the light-induced performance. The present work
      considers a combined effect of several key performance-related properties (KPPs)
      on photocatalytic activity of TiO2 (rutile), including the chemical potential of
      electrons (Fermi level), the concentration of surface active sites, and charge
      transport, in addition to the band gap. The KPPs have been modified using defect
      engineering. This approach led to imposition of different defect disorders and
      the associated KPPs, which are defect-related. This work shows, for the first
      time, a competitive influence of different KPPs on photocatalytic activity that
      was tested using oxidation of methylene blue (MB). It is shown that the increase
      of oxygen activity in the TiO2 lattice from 10(-12) Pa to 10(5) Pa results in (i)
      increase in the band gap from 2.42 to 2.91 eV (direct transitions) or 2.88 to 3
      eV (indirect transitions), (ii) increase in the population of surface active
      sites, (iii) decrease of the Fermi level, and (iv) decrease of the charge
      transport. It is shown that the observed changes in the photocatalytic activity
      are determined by two dominant KPPs: the concentration of active surface sites
      and the Fermi level, while the band gap and charge transport have a minor effect
      on the photocatalytic performance. The effect of the defect-related properties on
      photoreactivity of TiO2 with water is considered in terms of a theoretical model
      offering molecular-level insight into the process. 

PMID- 26294288
TI  - Probing relevant ingredients in mean-field approaches for the athermal rheology
      of yield stress materials.
AB  - Although the notion of mechanical noise is expected to play a key role in the non
      linear rheology of athermally sheared amorphous systems, its characterization has
      so far remained elusive. Here, we show using molecular dynamic simulations that
      in spite of the presence of strong spatio-temporal correlations in the system,
      the local stress exhibits normal diffusion under the effect of the mechanical
      noise in the finite driving regime. The diffusion constant appears to be
      proportional to the mean plastic activity. Our data suggests that the
      corresponding proportionality constant is density independent, and can be
      directly related to the specific form of the rheological flow curve, pointing the
      way to a generic way of modeling mechanical noise in mean-field equations. 

PMID- 26294287
TI  - Bacterial Transformation and the Origins of Epidemics in the Interwar Period: The
      Epidemiological Significance of Fred Griffith's "Transforming Experiment".
AB  - Frederick Griffith (1879-1941) was an English bacteriologist at the Pathological
      Laboratory of the Ministry of Health in London who believed that progress in the
      epidemiology and control of infectious diseases would come only with more precise
      knowledge of the identity of the causative microorganisms. Over the years,
      Griffith developed and expanded a serological technique for identifying
      pathogenic microorganisms, which allowed the tracing of the sources of infectious
      disease outbreaks: slide agglutination. Yet Griffith is not remembered for his
      contributions to the biology and epidemiology of infectious diseases so much as
      for discovering the phenomenon known as 'transformation'. Griffith's discovery,
      for many, was a pure case of serendipity whose biological relevance had also
      largely escaped him. In this paper, I argue that the key to understanding the
      significance of bacterial transformation - and the scientific legacy of Fred
      Griffith - rests not only on it initiating a cascade of events leading to
      molecular genetics but also on its implications for epidemiology based on the
      biology of host-parasite interactions. Looking at Griffith's entire career,
      instead of focusing only on the transformation study, we can better appreciate
      the place of the latter within Griffith's overall contributions. Presented in
      this way, Griffith's experiment on bacterial transformation also ceases to appear
      as an anomaly, which in turn leads us to rethink some of the most prevalent
      historical conceptions about his work.

PMID- 26294289
TI  - Statistical comparison of dissolution profiles.
AB  - Statistical methods to assess similarity of dissolution profiles are introduced.
      Sixteen groups of dissolution profiles from a full factorial design were used to
      demonstrate implementation details. Variables in the design include drug
      strength, tablet stability time, and dissolution testing condition. The 16 groups
      were considered similar when compared using the similarity factor f2 (f2 > 50).
      However, multivariate ANOVA (MANOVA) repeated measures suggested statistical
      differences. A modified principal component analysis (PCA) was used to describe
      the dissolution curves in terms of level and shape. The advantage of the modified
      PCA approach is that the calculated shape principal components will not be
      confounded by level effect. Effect size test using omega-squared was also used
      for dissolution comparisons. Effects indicated by omega-squared are independent
      of sample size and are a necessary supplement to p value reported from the MANOVA
      table. Methods to compare multiple groups show that product strength and
      dissolution testing condition had significant effects on both level and shape.
      For pairwise analysis, a post-hoc analysis using Tukey's method categorized three
      similar groups, and was consistent with level-shape analysis. All these methods
      provide valuable information that is missed using f2 method alone to compare
      average profiles. The improved statistical analysis approach introduced here
      enables one to better ascertain both statistical significance and clinical
      relevance, supporting more objective regulatory decisions. 

PMID- 26294290
TI  - New Delhi metallo-beta-lactamase and OXA-48 carbapenemases in Gram-negative
      bacilli isolates in Libya.

PMID- 26294293
TI  - Strontium ranelate as an adjuvant for fracture healing: clinical, radiological,
      and ultrasound findings in a randomized controlled study on wrist fractures.
AB  - This randomized and controlled study evaluated the effect of therapy with
      strontium ranelate on callus formation in wrist fractures and its incidence in
      wrist recovery. Radiographic healing, progression of clinical recovery, and
      callus quality with ultrasound were evaluated. No statistically significant
      benefit of therapy was found. INTRODUCTION: Fracture prevention is the main goal
      of any therapy for osteoporosis. Various drugs used in osteoporosis treatment
      have the theoretical premises to promote fracture healing and osseointegration.
      In this study, the effect of strontium ranelate on callus formation in wrist
      fractures was evaluated and whether it could lead to clinically relevant
      modification of wrist recovery; having strontium ranelate osteoinductive
      properties, it could be used, if effective, as an adjunct in fracture healing for
      a faster and functionally better recovery and, at the same time, in starting
      proper therapy in osteoporotic patients with fragility fractures. METHODS: We
      considered only patients older than 60 years who had suffered wrist fracture and
      received nonoperative treatment with manual reduction of the fracture and cast
      for 35 days. Forty patients were included and randomly assigned to one of two
      groups: group A [patients treated with calcium (1200 mg/day) and vitamin D (800
      IU/day)] and group B [patients treated with calcium (1200 mg/day) and vitamin D
      (800 IU/day) associated with strontium ranelate 2 g daily]. Radiographic healing
      was evaluated through the bone callus formation, cortical continuity, and density
      of the callus. A clinical evaluation using Castaing's criteria was carried out 2
      and 3 months following the fracture together with an ultrasound study of callus
      density and vessels. RESULTS: A parametric analysis of the X-ray data, clinical
      evaluation, and ultrasonography results showed that there were no statistically
      significant differences in the two groups (p > 0.05 for all data). CONCLUSION: In
      analyzing the data obtained, we concluded that strontium ranelate administered in
      acute phase did not improve nor accelerate wrist fracture healing in our
      population.

PMID- 26294291
TI  - Inflammation and the bone-vascular axis in end-stage renal disease.
AB  - Bone loss and vascular calcification coincide in patients with end-stage renal
      disease, similar as to what is observed in the general population. In the present
      bone biopsy study, we provide further evidence that (micro-)inflammation may
      represent a common soil for both diseases. INTRODUCTION: Vascular calcification
      is a common complication of end-stage renal disease (ESRD) and is predictive of
      subsequent cardiovascular disease and mortality. Mounting evidence linking bone
      disorders with vascular calcification has contributed to the development of the
      concept of the bone-vascular axis. Inflammation is involved in the pathogenesis
      of both disorders. The aim of the present study was to evaluate the relationship
      between aortic calcification, inflammation, and bone histomorphometry in patients
      with ESRD. METHODS: Parameters of inflammation and mineral metabolism were
      assessed in 81 ESRD patients (55 +/- 13 year, 68 % male) referred for renal
      transplantation. Static bone histomorphometry parameters were determined on
      transiliac bone biopsies performed during the transplant procedure. Aortic
      calcification was quantified on lateral lumbar X-rays using the Kauppila method.
      RESULTS: Aortic calcification, low bone turnover, and low bone area were observed
      in 53, 37, and 21 % of patients respectively. Inflammatory markers were found to
      be independently associated with aortic calcification (hsIL-6) and low bone area
      (TNF-alpha). Low bone area associated with aortic calcification, independent of
      age, diabetes, and inflammation. CONCLUSIONS: Low bone area and inflammation
      associates with aortic calcification, independent of each other and traditional
      risk factors. Our data emphasize the role of (micro-)inflammation in the bone
      vascular axis in CKD.

PMID- 26294292
TI  - Elevated incidence of fractures in women with invasive breast cancer.
AB  - This study evaluates the incidence of bone fractures in women with BC.We found
      that women with invasive breast cancer are at an increased risk for bone
      fractures, with fractures most commonly occurring at lower extremity and
      vertebral sites. The risk is further increased in women undergoing cancer
      therapy. INTRODUCTION: Bone loss and fractures in breast cancer have generally
      been attributed to aromatase inhibitor use. This study assessed the incidence of
      fractures after invasive breast cancer diagnosis and evaluated bone density and
      FRAX risk calculation at time of fracture occurrence. METHODS: Retrospective
      cohort study of women with invasive breast cancer [June 2003-December 2011] who
      participated in an academic hospital based genetic biobank. Demographic and
      clinical characteristics were abstracted from the electronic medical record
      (EMR). RESULTS: A total of 422 women with invasive breast cancer were assessed;
      79 (28 %) sustained fractures during the observation period; fractures occurred
      at multiple skeletal sites in 27 cases (116 fractures). The incidence of
      fractures was 40 per 1000 person-years. Women who sustained fractures were mostly
      white and had a family history of osteoporosis (36.9 %, p = 0.03) or history of a
      prior fracture (6/79, p = 0.004). Fractures occurred 4.0 years (range 0-12 years)
      after cancer diagnosis. Fracture cases had femoral neck bone mineral density
      (BMD) of 0.72 + 0.12 g/cm(2), T-score of -1.2, that is, within the low bone mass
      range. Fractures most commonly occurred in lower extremities, vertebral, and
      wrist sites. Hip fractures accounted for 11 % of fractures, occurring at a median
      age of 61 years. CONCLUSIONS: Fractures occur shortly after commencing cancer
      therapy. Rapid bone loss associated with cancer therapy may precipitate
      fractures. Fractures occur at relatively higher BMD in BC. Occurrence of
      fractures in invasive breast cancer raises the possibility of cancer-induced
      impairment in bone quality.

PMID- 26294294
TI  - Reducing glucocorticoid dosage improves serum osteocalcin in patients with
      rheumatoid arthritis-results from the TOMORROW study.
AB  - Decreasing the daily dose of glucocorticoids improved bone metabolic marker
      levels in patients with rheumatoid arthritis. However, changes in disease
      activity did not influence bone metabolism. Bone metabolism might thus remain
      uncontrolled even if disease activity is under good control. Decreasing
      glucocorticoid dosage appears important for improving bone metabolism.
      INTRODUCTION: Patients with rheumatoid arthritis (RA) develop osteoporosis more
      frequently than healthy individuals. Bone resorption is increased and bone
      formation is inhibited in patients with RA, and glucocorticoid negatively affects
      bone metabolism. We aimed to investigate factors influencing bone metabolic
      markers in patients with RA. METHODS: We started the 10-year prospective cohort
      Total Management of Risk Factors in Rheumatoid Arthritis Patients to Lower
      Morbidity and Mortality (TOMORROW) study in 2010. We compared changes in urinary
      cross-linked N-telopeptide of type I collagen (uNTx) and serum osteocalcin (OC),
      as markers of bone resorption and formation, respectively, in 202 RA patients and
      age- and sex-matched volunteers between 2010 and 2011. We also investigated
      factors influencing DeltauNTx and DeltaOC in the RA group using multivariate
      analysis. RESULTS: Values of DeltauNTx were significantly lower in patients with
      RA than in healthy controls (-0.51 vs. 7.41 nmol bone collagen equivalents
      (BCE)/mmol creatinine (Cr); p = 0.0013), whereas DeltaOC values were
      significantly higher in RA patients (0.94 vs. 0.37 ng/ml; p = 0.0065). Changes in
      prednisolone dosage correlated negatively with DeltaOC (beta = -0.229, p =
      0.001), whereas changes in disease activity score, bisphosphonate therapy, and
      period of biologics therapy did not correlate significantly with DeltaOC. No
      significant correlation was seen between DeltauNTx and change in prednisolone
      dosage. CONCLUSIONS: Decreased glucocorticoid dosage improved bone metabolic
      markers in RA, but disease activity, bisphosphonate therapy, and period of
      biologics therapy did not influence levels of bone metabolic markers. Decreasing
      glucocorticoid dosage appears important for improving bone metabolic marker
      profiles in patients with RA.

PMID- 26294296
TI  - Tumor Texture Analysis in PET: Where Do We Stand?

PMID- 26294295
TI  - Comparison of 18F-FDG PET/CT for Systemic Staging of Newly Diagnosed Invasive
      Lobular Carcinoma Versus Invasive Ductal Carcinoma.
AB  - Although guidelines such as those of the National Comprehensive Cancer Network
      consider (18)F-FDG PET/CT for systemic staging of newly diagnosed stage III
      breast cancer patients, factors in addition to stage may influence the utility of
      PET/CT. Because invasive lobular carcinoma (ILC) is less conspicuous than
      invasive ductal carcinoma (IDC) on (18)F-FDG PET, we hypothesized that tumor
      histology may be one such factor. We evaluated PET/CT systemic staging of
      patients newly diagnosed with ILC compared with IDC. METHODS: In this
      Institutional Review Board-approved retrospective study, our Hospital Information
      System was screened for ILC patients who underwent PET/CT in 2006-2013 before
      systemic or radiation therapy. Initial stage was determined from examination,
      mammography, ultrasound, MR, or surgery. PET/CT was performed to identify
      unsuspected distant metastases. A sequential cohort of stage III IDC patients was
      evaluated for comparison. Upstaging rates were compared using the Pearson chi(2)
      test. RESULTS: The study criteria were fulfilled by 146 ILC patients. PET/CT
      revealed unsuspected distant metastases in 12 (8%): 0 of 8 with initial stage I,
      2 of 50 (4%) stage II, and 10 of 88 (11%) stage III. Upstaging to IV by PET/CT
      was confirmed by biopsy in all cases. Three of 12 upstaged patients were upstaged
      only by the CT component of the PET/CT, as the metastases were not (18)F-FDG
      avid. In the comparison stage III IDC cohort, 22% (20/89) of patients were
      upstaged to IV by PET/CT. All 20 demonstrated (18)F-FDG-avid metastases. The
      relative risk of PET/CT revealing unsuspected distant metastases in stage III IDC
      patients was 1.98 times (95% confidence interval, 0.98-3.98) that of stage III
      ILC patients (P = 0.049). For (18)F-FDG-avid metastases, the relative risk of
      PET/CT revealing unsuspected (18)F-FDG-avid distant metastases in stage III IDC
      patients was 2.82 times (95% confidence interval, 1.26-6.34) that of stage III
      ILC patients (P = 0.007). CONCLUSION: (18)F-FDG PET/CT was more likely to reveal
      unsuspected distant metastases in stage III IDC patients than in stage III ILC
      patients. In addition, some ILC patients were upstaged by non-(18)F-FDG-avid
      lesions visible only on the CT images. Overall, the impact of PET/CT on systemic
      staging may be lower for ILC patients than for IDC patients.

PMID- 26294297
TI  - Quantification of 11C-Laniquidar Kinetics in the Brain.
AB  - Overexpression of the multidrug efflux transport P-glycoprotein may play an
      important role in pharmacoresistance. (11)C-laniquidar is a newly developed
      tracer of P-glycoprotein expression. The aim of this study was to develop a
      pharmacokinetic model for quantification of (11)C-laniquidar uptake and to assess
      its test-retest variability. METHODS: Two (test-retest) dynamic (11)C-laniquidar
      PET scans were obtained in 8 healthy subjects. Plasma input functions were
      obtained using online arterial blood sampling with metabolite corrections derived
      from manual samples. Coregistered T1 MR images were used for region-of-interest
      definition. Time-activity curves were analyzed using various plasma input
      compartmental models. RESULTS: (11)C-laniquidar was metabolized rapidly, with a
      parent plasma fraction of 50% at 10 min after tracer injection. In addition, the
      first-pass extraction of (11)C-laniquidar was low. (11)C-laniquidar time-activity
      curves were best fitted to an irreversible single-tissue compartment (1T1K) model
      using conventional models. Nevertheless, significantly better fits were obtained
      using 2 parallel single-tissue compartments, one for parent tracer and the other
      for labeled metabolites (dual-input model). Robust K1 results were also obtained
      by fitting the first 5 min of PET data to the 1T1K model, at least when 60-min
      plasma input data were used. For both models, the test-retest variability of
      (11)C-laniquidar rate constant for transfer from arterial plasma to tissue (K1)
      was approximately 19%. CONCLUSION: The accurate quantification of (11)C
      laniquidar kinetics in the brain is hampered by its fast metabolism and the
      likelihood that labeled metabolites enter the brain. Best fits for the entire 60
      min of data were obtained using a dual-input model, accounting for uptake of
      (11)C-laniquidar and its labeled metabolites. Alternatively, K1 could be obtained
      from a 5-min scan using a standard 1T1K model. In both cases, the test-retest
      variability of K1 was approximately 19%.

PMID- 26294298
TI  - The Theranostic PSMA Ligand PSMA-617 in the Diagnosis of Prostate Cancer by
      PET/CT: Biodistribution in Humans, Radiation Dosimetry, and First Evaluation of
      Tumor Lesions.
AB  - PET imaging with the prostate-specific membrane antigen (PSMA)-targeted
      radioligand (68)Ga-PSMA-11 is regarded as a significant step forward in the
      diagnosis of prostate cancer (PCa). More recently, a PSMA ligand was developed
      that can be labeled with (68)Ga, (111)In, (177)Lu, and (90)Y. This ligand, named
      PSMA-617, therefore enables both diagnosis and therapy of PCa. The aims of this
      evaluation were to clinically investigate the distribution of (68)Ga-PSMA-617 in
      normal tissues and in PCa lesions as well as to evaluate the radiation exposure
      by the radioligand in PET imaging. METHODS: Nineteen patients, most of them with
      recurrent PCa, were referred for (68)Ga-PSMA-617 PET/CT. The quantitative
      assessment of tracer uptake of several organs and of 53 representative tumor
      lesions was performed in 15 patients at 1 and 3 h after injection. In 4
      additional patients, the same procedure was conducted at 5 min, 1 h, 2 h, 3 h, 4
      h, and 5 h after injection. On the basis of the data for these 4 patients (mean
      injected dose, 231 MBq), the radiation exposure of a (68)Ga-PSMA-617 PET/CT was
      identified. RESULTS: Intense tracer uptake was observed in the kidneys and
      salivary glands. In 14 of 19 patients (73.7%), at least 1 lesion suspected of
      being a tumor was detected at 3 h after injection. Of 53 representative tumor
      lesions selected at 3 h after injection, 47 lesions were visible at 1 h after
      injection. The mean tumor-to-background ratio for maximum standardized uptake
      value was 20.4 +/- 17.3 (range, 2.3-84.0) at 1 h after injection and 38.2 +/-
      38.6 (range, 3.6-154.3) at 3 h after injection. The average radiation exposure
      (effective dose) was approximately 0.021 mSv/MBq. CONCLUSION: Within healthy
      organs, the kidneys and salivary glands showed the highest (68)Ga-PSMA-617
      uptake. The radiation exposure was relatively low. (68)Ga-PSMA-617 shows PCa
      lesions with high contrast. Images obtained between 2 and 3 h after injection
      seem to be the best option with regard to radiotracer uptake and tumor contrast.
      Later images can help to clarify unclear lesions.

PMID- 26294299
TI  - 18F-Fluoride PET in the Assessment of Malignant Bone Disease.

PMID- 26294303
TI  - 90Y-DOTATOC as a Therapeutic Option for Complex Recurrent or Progressive
      Meningiomas.
AB  - The standard treatment of meningiomas is surgery or radiotherapy. Complex,
      especially recurrent or progressive cases, may exhibit tumor growth involving
      critical neurovascular structures or diffuse growth, resulting in limited
      efficacy and higher risk of standard treatment. We evaluated whether somatostatin
      receptor-targeted radionuclide therapy with (90)Y-DOTATOC may be a therapeutic
      option. METHODS: Fifteen patients with recurrent or progressive meningiomas after
      multimodal pretreatment or unfavorable medical risk profile were treated with
      systemic (90)Y-DOTATOC. Endpoints were progression-free survival and toxicity.
      RESULTS: Usually applied doses were 7,400 MBq/m(2) of (90)Y-DOTATOC in 2
      fractions. Mean observation time was 49.7 mo (range, 12-137 mo). Overall median
      progression-free survival was at least 24 mo. Toxicity was moderate, mostly
      hematologic (n = 8) and transient. CONCLUSION: (90)Y-DOTATOC therapy is feasible
      and may represent a promising second- or third-line option for complex
      meningiomas, which are progressive or otherwise not treatable with a reasonable
      risk-benefit ratio.

PMID- 26294304
TI  - Nanoparticles for Cardiovascular Imaging and Therapeutic Delivery, Part 2:
      Radiolabeled Probes.
AB  - Nanoparticulate imaging agents and therapeutics have proven to be valuable tools
      in preclinical cardiovascular disease research. Because of their distinct
      properties and significant functional versatility, nanoparticulate imaging agents
      afford certain capabilities that are typically not provided by traditional small
      molecule agents. This review is the second in a two-part series covering
      nanoparticulate imaging agents and theranostics. It highlights current examples
      of radiolabeled nanoparticulate probes in preclinical cardiovascular research and
      demonstrates their utility in applications such as blood pool imaging and
      molecular imaging of ischemia, angiogenesis, atherosclerosis, and inflammation.
      These agents provide valuable insight into the molecular and cellular mechanisms
      of cardiovascular disease and illustrate both the limitations and the significant
      potential of nanoparticles in diagnostic and therapeutic applications. Further
      technologic development to improve performance, address safety concerns, and
      fulfil regulatory obligations is required for clinical translation of these
      emergent technologies. 

PMID- 26294306
TI  - Delay in the diagnosis of tuberculosis.

PMID- 26294305
TI  - Improved RT-PCR Assay to Quantitate the Pri-, Pre-, and Mature microRNAs with
      Higher Efficiency and Accuracy.
AB  - Understanding of the functional significance of microRNAs (miRNAs) requires
      efficient and accurate detection method. In this study, we developed an improved
      miRNAs quantification system based on quantitative real-time polymerase chain
      reaction (qRT-PCR). This method showed higher efficiency and accuracy to survey
      the expression of primary miRNAs (pri-miRNAs), precursor miRNAs (pre-miRNAs), and
      mature miRNAs. Instead of relative quantification method, we quantified the pri
      miRNAs and pre-miRNAs with absolute qRT-PCR based on SYBR Green I fluorescence.
      This improvement corrected for the inaccuracy caused by the differences in
      amplicon length and PCR efficiency. We also used SYBR Green method to quantify
      mature miRNAs based on the stem-loop qRT-PCR method. We extended the pairing part
      of the stem-loop reverse transcript (RT) primer from 6 to 11 bp, which greatly
      increased the efficiency of reverse transcription PCR (RT-PCR). The performance
      of the improved RT primer was tested using synthetic mature miRNAs and tissue RNA
      samples. Results showed that the improved RT primer demonstrated dynamic range of
      seven orders of magnitude and sensitivity of detection of hundreds of copies of
      miRNA molecules. 

PMID- 26294301
TI  - Multimodality Brain Tumor Imaging: MR Imaging, PET, and PET/MR Imaging.
AB  - Standard MR imaging and CT are routinely used for anatomic diagnosis in brain
      tumors. Pretherapy planning and posttreatment response assessments rely heavily
      on gadolinium-enhanced MR imaging. Advanced MR imaging techniques and PET imaging
      offer physiologic, metabolic, or functional information about tumor biology that
      goes beyond the diagnostic yield of standard anatomic imaging. With the advent of
      combined PET/MR imaging scanners, we are entering an era wherein the
      relationships among different elements of tumor metabolism can be simultaneously
      explored through multimodality MR imaging and PET imaging. The purpose of this
      review is to provide a practical and clinically relevant overview of current
      anatomic and physiologic imaging of brain tumors as a foundation for further
      investigations, with a primary focus on MR imaging and PET techniques that have
      demonstrated utility in the current care of brain tumor patients. 

PMID- 26294307
TI  - AUDITORY TEMPORAL PROCESSING TESTS - NORMATIVE DATA FOR POLISH-SPEAKING ADULTS.
AB  - BACKGROUND: Several subjects exposed to neurotoxins in the workplace need to be
      assessed for central auditory deficit. Although central auditory processing tests
      are widely used in other countries, they have not been standardized for the
      Polish population. The aim of the study has been to evaluate the range of
      reference values for 3 temporal processing tests: the duration pattern test
      (DPT), the frequency pattern test (FPT) and the gaps in noise test (GIN).
      MATERIAL AND METHODS: The study included 76 normal hearing individuals (38 women,
      38 men) at the age of 18 to 54 years old (mean +/- standard deviation: 39.4+/
      9.1). All study participants had no history of any chronic disease and underwent
      a standard ENT examination. RESULTS: The reference range for the DPT was
      established at 55.3% or more of correct answers, while for the FPT it stood at
      56.7% or more of correct answers. The mean threshold for both cars in the GIN
      test was defined as 6 ms. In this study there were no significant associations
      between the DPT, FPT and GIN results and age or gender. Symmetry between the ears
      in the case of the DPT, FPT and GIN was found. CONCLUSIONS: Reference ranges
      obtained in this study for the DPT and FPT in the Polish population are lower
      than reference ranges previously published for other nations while the GIN test
      results correspond to those published in the related literature. Further
      investigations are needed to explain the discrepancies between normative values
      in Poland and other countries and adapt tests for occupational medicine purposes.

PMID- 26294309
TI  - WORKING TIME INTERVALS AND TOTAL WORK TIME ON NURSING POSITIONS IN POLAND.
AB  - BACKGROUND: For the last few years a topic of overwork on nursing posts has given
      rise to strong discussions. The author has set, herself a goal of answering the
      question if it is a result of real overwork of this particular profession or
      rather commonly assumed frustration of this professional group. The aim of this
      paper is to conduct the analysis of working time on chosen nursing positions in
      relation to measures of time being used as intervals in the course of conducting
      standard professional activities during one working day. MATERIAL AND METHODS:
      Research material consisted of documentation of work time on chosen nursing
      workplaces, compiled between 2007-2012 within the framework of a nursing course
      at the Pomeranian Medical University in Szczecin. As a method of measurement a
      photograph of a working day has been used. Measurements were performed in
      institutions located in 6 voivodeships in Poland. RESULTS: Results suggest that
      only 6.5% of total of surveyed representatives of nurse profession spends proper
      amount of time (meaning: a time set by the applicable standards) on work
      intervals during a working day. CONCLUSIONS: The scale of the phenomenon
      indicates excessive workload for nursing positions, which along with a longer
      periodof time, longer working hours may cause decrease in efficiency of work and
      cause a drop in quality of provided services.

PMID- 26294308
TI  - CIGARETTE SMOKING AMONG 17-18 YEAR OLD ADOLESCENTS - PREVALENCE AND ASSOCIATION
      WITH SOCIODEMOGRAPHIC, FAMILIAL, SPORT, AND SCHOLASTIC. FACTORS.
AB  - BACKGROUND: Though adolescence is recognised as a critical period for smoking
      prevention, there is a lack of research focused on this issue in Kosovo. The aim
      of this study has been to examine the gender-specific factors of influence
      (predictors) for smoking among adolescents in Pristina, Kosovo. MATERIAL AND
      METHODS: The study sample comprised 1002 adolescents at the age of 17-18 (366
      boys, 636 girls), all of whom were in the school's 12th grade. The predictors
      included sociodemographic variables, familial (i.e.,parental) monitoring,
      parents' educational background, and sport-related factors. The Chi2 and forward
      stepwise logistic regression analyses with a dichotomous criterion (smoking vs.
      non-smoking) were applied. RESULTS: The incidence of smoking was high (31% and
      40% smokers, including 7% and 12% daily smokers for girls and boys,
      respectively). The regression model revealed more frequent absence from
      school(odds ratio (OR): 1.544; 95% confidence interval (Ci): 1.063-2.243), more
      unexcused school absences (OR: 1.360; 95% CI: 1.029-1.796), and frequent parental
      questioning (OR: 1.530; 95% CI: 1.020-2.295) to be significant predictors'of
      smoking among boys. For girls, a higher risk of smoking was associated with lower
      scholastic achievement (OR: 1.467; 95% CI: 1.089-1.977), more frequent absence
      from school (OR: 1.565; 95% CI: 1.137-2.155), increased conflict with parents
      (OR: 1.979; 95% CI: 1.405-2.789),and a self-declared perception of less parental
      care (OR: 0.602; 95% CI: 0.377-0.962). Sports were not found to be strongly
      related to smoking. However, a high riskof daily smoking was found among boys who
      participated in team sports and subsequently quit. CONCLUSIONS: This study
      reinforces the need for gender- and culture-specific approaches to studying the
      factors that influence smoking among adolescents.

PMID- 26294310
TI  - [ASSESSMENT OF THE AUDIBILITY AREA OF AUDITORY DANGER SIGNALS PRODUCED BY
      INDUSTRIAL TRUCK].
AB  - BACKGROUND: The aim of the study was to answer the question what is the
      audibility area of auditory danger signal emitted by an industrial truck in the
      noisy environment. MATERIAL AND METHODS: The sound pressure level of the signal
      produced by the truck horn was measured in 12 directions around the truck, at a
      distance of 2 to 10 m. It was analyzed, in which places around the truck,
      auditory danger signal emitted by this truck can be reliably recognized
      (according to PN-EN ISO 7731). The analysis included 2 types of masking noise.
      RESULTS: The calculated audibility area in the presence of one type of the noise
      is about 2-8 m in front of the truck and up to about 3 m on both sides of the
      truck. Furthermore, itis audible from the rear of the truck, in the range of
      about 1.5-10 m and 3-7 m, respectively onthe right and left axes of the truck. In
      the case of high-frequencynoise, despite of its.higher A-weighted equivalent
      sound'pressure level (12.5 dB), the audibility area is not significantly
      different. CONCLUSIONS: The presented method of analysis allowed to determine the
      audibility area of auditory danger signal in the case of considered industrial
      truck, at the specific workplace. This method can be used in the future to
      evaluate any auditory danger signal at the workplace, where noise is present. The
      caselstudy showed that it is possible to encounter a situation where the use of
      hearing protection devices at the workplace cannot affect the audibility area.

PMID- 26294311
TI  - [TECHNICAL ASPECTS OF EXPOSURE TO MAGNETIC FIELDS OF EXTREMELY LOW FREQUENCIES
      (ELF) IN BIOMEDICAL RESEARCH].
AB  - BACKGROUND: Experiments on the electromagnetic field influence on organisms are
      an important part of biophysical studies. It is an interdisciplinary research
      spanning biology and medicine with the engineering in generation and measurement
      of electromagnetic fields. The aim of the study consists the analysis of
      parameters estimations and measurements of extremely low frequency magnetic field
      (ELF MF) as well as exposure systems parameters in biomedical research. MATERIAL
      AND METHODS: Experiments were performed on 2 most popular low magnetic field
      exposure systems: the solenoid and Helmholtz coils. A theoretical analysis and a
      measurement verification of the magnetic field distribution inside the systems
      were carried out to evaluate the homogeneity of the magnetic field. Additional
      factors, vibrations and temperature changes, affecting the assessment of the
      biological effects of magnetic field exposure were also examined. RESULTS: Based
      on the study results, a comparative analysis of solenoids and Helmholtz coils as
      the magnetic field exposure systems was presented. Proposals for the description
      of magnetic field exposure were also formulated. CONCLUSIONS: The authors
      emphasize the importance of a conscious choice of exposure conditions and their
      explicit description. These are fundamental requirements for both the
      reproduction of experiniental conditions and the verification of results.

PMID- 26294312
TI  - [ASSESSMENT OF OCCUPATIONAL EXPOSURE TO RADIO FREQUENCY ELECTROMAGNETIC FIELDS].
AB  - BACKGROUND: European Union Directive 2013/35/UE provides for the implementation
      of EU regulations into national legislation. Our aim is to assess actual health
      hazards from radiofrequency eldctromagnetic field (RF EMF) (range: 100 kHz - 300
      GHz) and indicate workplaces with the highest risk to employee health. MATERIAL
      AND METHODS: Data from measurements of RF EMF performed by the Laboratory of
      Electromagnetic Hazards in Nofer Institute of Occupational Medicine (Lodz,
      Poland) were analyzed. The analysis covered the results of electric field
      intensity (E) for over 450 selected items. The ranges of protection zones and the
      extent to which maximum admissible intensity (MAI) values were also analyzed. The
      determinations and'measurements of EMF in the work environment met the
      requirements of Polish Standard, while Polish regulations on the MAI values were
      used as the criterion for the assessment of the exposure. RESULTS: The highest
      values of E field intensity at workplaces were measured for: electrosurgery, to
      400 V/m, and short-wave diathermy units, to 220 V/m, dielectric welders to 240
      V/m, within the FM radio antenna systems, to 180 V/m. The widest protection zones
      were noted for prototype research instruments, short-wave diathermy units, and
      dielectric welders. The most excessive (up to 12-fold MAI) values were recorded
      for dielectric welders, short-wave diathermy units (up to 11-fold) and microwave
      diathermy units (up to 8-fold). CONCLUSIONS: Our results have confirmed the high
      RF EMF values for physiotherapists, operators of dielectric welders, and mast
      maintenance workers in radio com munication facilities (especially radio and TV
      broadcasting stations).

PMID- 26294313
TI  - [TYPE A BEHAVIOUR AS A PREDICTOR OF BURNOUT AND JOB SATISFACTION IN INTENSIVE
      CARE UNITS NURSES].
AB  - BACKGROUND: Working at intensive care unit (ICU) is one ot the most difticult and
      taxing nursing speciaites. It demans not only extensive knowledge and
      professional skills but also specific personality temperamental dispositions. The
      aim of the study was to verify if typeA behavior (TAB) is a predictor ofburnout
      and job satisfaction in ICU nurses and if this effect still exists after
      controlling for selected demographic and job characteristics. MATERIAL AND
      METHODS: The study group consisted of 99 nurses (77 women), aged 24-58 (mean (M)
      = 32.33; standard deviation (SD) = 8:81) working at ICU. The following tools were
      used: to measure TAB - Type A Behavior Survey BWZ by Wrzesniewski; job burnout -
      the Oldenburg Burnout Inventory OLBI by Demerouti et al.; and job satisfaction -
      the Job Satisfaction Scale by Zalewska. RESULTS: The results of hierarchical
      regression analyses showed that after controlling for selected demographic and
      job characteristics, tendency for aggressibn was a predictor of higher
      exhaustion, disengagement and lower job satisfaction. Achievement striving and
      tendency to dominate were related to higher job satisfaction and lower
      exhaustion, respectively. Significant predictors of professional functioning were
      also: duty work system, place of living and gender. CONCLUSIONS: The results of
      the study.confirmed that all 3 content features of TAB were significant
      predictors of job functioning of ICU nurses. They also indicate that considering
      TAB in the context of individual adjustment to the environment of the job at ICU
      would be a valuable direction forfuture research.

PMID- 26294314
TI  - [THE APPLICATION OF SHORT-TERM EFFICIENCY ANALYSIS IN DIAGNOSING OCCUPATIONAL
      VOICE DISORDERS].
AB  - BACKGROUND: An objective determination of the range of vocal efficiency is rather
      difficult. The aim of the study was to assess the possibility of application of
      short-term acoustic efficiency analysis in diagnosing occupational voice
      disorders. MATERIAL AND METHODS: The study covered 98 people (87 women and 11
      men) diagnosed with occupational dysphonia throuigh videostroboscopic
      examination. The control group comprised 100 people (81 women and 19 men) with
      normal voices. The short-term acoustic analysis was carried out by means of
      DiagnoScope software, including classical parameters (Jitter group, Shimmer group
      and the assessment of noise degree NHR), as well as new short-term efficiency
      parameters determined in a short time period during sustained phonation of the
      vowel "a." The results were then compared. Results: The values of all the
      examined classical parameters were considerably higher in the study group of
      pathological voices than in the control group of normal voices (p = 0.00). The
      aerodynamic parameter, maximum phonation time, was significantly shorter by over
      0.5 s in the study group than in the control group. The majority of the acoustic
      efficiency parameters were also considerably worse in the study group of subjects
      with occupational dysphonia than in the control group (p = 0.00). Moreover, the
      correlation between the efficiency parameters and most of the classical acoustic
      parameters in the study group implies that for the voices with occupational
      pathology the decreased efficiency of the vocal apparatus is reflected in the
      acoustic voice structure. CONCLUSIONS: Effliciency parameters determined during
      short-term acoustic analysis can be an objective indicator of the decreased
      phonatory function of the larnx, useful in diagnosing occupational vocal
      pathology.

PMID- 26294315
TI  - [ORGANOPHOSPHORUS FLAME RETARDANTS - TOXICITY AND INFLUENCE ON HUMAN HEALTH].
AB  - Organophosphorus flame retardants (flame retardants, FRs) have been used for
      several decades in many industries, including the production of dyes, varnishes,
      adhesives, synthetic resins, polyvinyl chloride, hydraulic fluids, plastics and
      textiles. Their importance in recent times has increased due to i.a.,
      significantly reduced use of polybrominated diphenyl ethers (PBDEs) - persistent
      organic pollutants, dangerous for the environment. The aim of this study was to
      review the available literature data concerning phosphorous FRs primarily for
      neurotoxic, fertility, reproductive and carcinogenic effects. The analysis
      concerned the following most commonly used substances: tris(2
      ethylhexyl)phosphate (TEHP), tris(2-butoxyethyl)phosphate (TBEP), triphenyl
      phosphate (TPP), tris(2-chloroethyl)phosphate (TCEP), tetrakis(hydroxymethyl)
      phosphonium chloride (THPC), tributyl phosphate (TBP), tricresyl phosphate (TCP),
      tris(2-chloroisopropyl)phosphate (TCPP), tris(1,3-dichloroisopropyl)phosphate
      (TDCP) and tetrakis(hydroxymethyl)phosphonium sulphate (THPS). In animal studies
      neurotoxic effects were found after exposure to TBEP, THPC, TBP and TCP, while in
      humans they were observed only after exposure to TCP. TCEP, THPS, TBP, TCP and
      TDCP caused disorders in fertility and/or fetal development of animals. Adverse
      effects on reproduction in humans may be caused by TPP, TCP, and TDCP. In
      laboratory animals the development of tumors was observed after high doses of
      TEHP, TCEP, TBP and TDCP. None of these compounds is classified as a human
      carcinogen. The environmental toxicity of phosphate FRs is low (except for TPP,
      TCEP and TBEP). They are not stable compounds, in living organisms they are
      metabolised and quickly excreted. Therefore, they can be used as an alternative
      to PBDEs.

PMID- 26294316
TI  - [METHOTREXATE - GENOTOXIC AND TERATOGENIC FOR MEDICAL STAFF OF ONCOLOGY WARDS?].
AB  - Methotrexate (MTX) is one of the most widely used cytostatic drugs belonging to
      the folic acid antagonists. It is a substance non-classified as a carcinogen in
      the European Union and by the International Agency for Research on Cancer (IARC)
      as there is no evidence of its carcinogenicity to humans and animals.
      Nevertheless, MTX has been placed on the list of dangerous drugs used in
      chemotherapy, mainly due to geniotoxic and teratogenic effects, causing
      developmental toxicity and reproductive toxicity. Methotrexate was determined in
      the hospital ward air during the preparation of a medicament at a level of 0.3
      mg/m3, as well as on protective gloves and preparatory room surfaces. In most
      research projects MTX was identified in the urine of health care workers,
      pharmacists and nursing staff. The highest cumulative concentration of MTX in 112
      urine samples was 1416 mg in workers preparing infusions for patients. Studies
      carried out in pharmacies revealed the presence of MTX in 60% of tests, and the
      maximum concentration of 15 ng/cm2 surface of the tray to count tablets. Legal
      exposure limit values for MTX in the work environment have not yet been
      established. Occupational exposure limits have been established by some
      manufacturers at the level of 0.0003-0.0025 mg/m3. There is an urgent need to
      establish normative values. It should also be emphasized that MTX is absorbed
      through the skin, which may significantly-increase the exposure and measuring its
      concentration in the work environment may not be sufficient to estimate the
      actual exposure.

PMID- 26294317
TI  - [ORGANIZATIONAL COMMITMENT AND WORK ENGAGEMENT - THEORETICAL CONCEPTIONS AND
      TERMINOLOGICAL PROBLEMS].
AB  - Engagement in professional activities and positive attitudes towards an
      organization are of significant importance to functioning and health of
      employees. Studies analysing the phenomena of employees' engagement and their
      relations with an organization undergo a dynamic development in both
      international and Polish research. Two theoretical conceptions: organizational
      commitment (by Meyer and Allen) and work engagement (by Schaufeli and Bakker)
      have become prominent in the field. They capture 2 similar, albeit distinct
      constructs. In English-language journals academics concentrate on theoretical and
      empirical analyses of similarities and differences between the 2 concepts, while
      in Polish publications scholars also have to deal with the issue of the original
      term translation. The problem lies mostly in Polish nomenclature of the
      dimensions proposed in both of these conceptions. Lack of common translations for
      different studies may cause confusion in this area of research. In the paper
      authors present a review of Polish translations of terms used in the discussed
      conceptions and a linguistic analysis of terms, both in English and in Polish.
      Authors provide solutions which could help to clarify terminology in Polish
      language publications concerning organizational commitment and work engagement.
      This allows for further development of research in this field.

PMID- 26294318
TI  - Factors affecting the occurrence of canine parvovirus in dogs.
AB  - Canine parvovirus (CPV) is the most important enteric virus infecting canids
      worldwide. The purpose of this study was to detect CPV in naturally infected dogs
      from several veterinary clinics distributed throughout Portugal between 2012 and
      2014 and to identify risk factors associated with CPV infection. From 209 dogs
      suspected of being infected with CPV, historical data and clinical signs were
      collected. Fecal samples were screened for CPV by PCR assay and those positive
      were confirmed by sequencing. The data was analyzed using logistic regression to
      investigate associations between each of the predisposing factors and CPV status.
      Of the samples collected, 77.5% tested CPV-positive. Statistical analysis showed
      that animals in the three age categories (p<0.001) were at list 12 times more
      likely to be CPV-positive than older animals. The anthelminthic treatment
      [OR=0.45, p=0.04] and the rectal temperature (hypothermia, [OR=0.12, p=0.004])
      contributed to decrease the likelihood of the dogs be infected with CPV. On the
      other hand, clinical signs such as depression [OR=4.4, p=0.02] and dehydration
      status [OR=2.38, p=0.001] made dogs more likely to be CPV-infected. The results
      indicate that although having a high morbidity, only 18% of the Portuguese dog
      population died in the study. Some of the risk factors identified in this study
      have not been commonly reported, yet they are easy to obtain and can be used as
      prognostic indicators in the veterinary practice. 

PMID- 26294319
TI  - Human dignity and the physician's conscience.

PMID- 26294321
TI  - Surface-confined Ullmann coupling of thiophene substituted porphyrins.
AB  - The covalent coupling of (5,10,15,20-tetrabromothien-2-ylporphyrinato)zinc(II)
      (TBrThP) molecules on the Ag(111) surface has been investigated under ultra-high
      vacuum conditions, using scanning tunnelling microscopy and x-ray photoelectron
      spectroscopy. The findings provide atomic-level insight into surface-confined
      Ullmann coupling of thiophene substituted porphyrins, analyzing the progression
      of organometallic intermediate to final coupled state. Adsorption of the TBrThP
      molecules on the Ag(111) surface at room temperature is found to result in the
      reductive dehalogenation of the bromothienyl substituents and the subsequent
      formation of single strand and crosslinked coordination networks. The coordinated
      substrate atoms bridge the proximal thienyl groups of the organometallic
      intermediate, while the cleaved bromine atoms are bound on the adjacent Ag(111)
      surface. The intermediate complex displays a thermal lability at ~423 K that
      results in the dissociation of the proximal thienyl groups with the concomitant
      loss of the surface bound bromine. At the thermally induced dissociation of the
      intermediate complex the resultant thienylporphyrin derivatives covalently
      couple, leading to the formation of a polymeric network of thiophene linked and
      meso-meso fused porphyrins. 

PMID- 26294320
TI  - Validating self-report and proxy reports of the Dexamethasone Symptom
      Questionnaire -Chronic for the evaluation of longer-term corticosteroid toxicity.
AB  - PURPOSE: In brain tumours, brain metastases or advanced cancer; treatment with
      corticosteroids, side effects can add to symptoms. These are best assessed by
      patients, complementing clinical assessment. We assessed the feasibility and
      validity of the Dexamethasone Symptom Questionnaire-Chronic (DSQ-Chronic),
      patient and caregiver versions. METHODS: A longitudinal cohort study was
      conducted, collecting clinician-rated toxicity, performance status, dexamethasone
      dose and DSQ-Chronic (patient and caregiver versions) at baseline, then 2, 4 and
      8 weeks later. Patients had a primary malignant brain tumour, brain metastases,
      or advanced cancer; Karnofsky Performance Status >=40 and predicted survival >=8
      weeks. Analysis included questionnaire completion rates, frequency and severity
      of dexamethasone-attributable side effects, agreement between patient and
      caregiver ratings, comparison with clinician-rated toxicity and correlation with
      performance status. RESULTS: Sixty-six patients were recruited (mean age 60
      years), with their caregivers. Completion of questionnaires was over 90% for the
      dyad at baseline but dropped over time, with caregiver completion rates higher at
      all timepoints. Agreement between patients and proxies was fair to moderate, and
      while proxies systematically overestimated symptom severity on DSQ-chronic total
      scores, the bias was less than 10 points. Patient and clinician agreement was
      higher for more objective symptoms. CONCLUSION: The DSQ-Chronic is feasible when
      the patient is relatively well. As capacity to complete the DSQ-Chronic
      diminishes, caregivers can be proxy-raters. Clinicians capture corticosteroid
      toxicities, which may not be obvious to the patient. The DSQ-Chronic, patient and
      caregiver versions, are useful tools to be used with clinician assessment.

PMID- 26294322
TI  - How and Why Does Ni(0) Promote Smooth Etheric C-O Bond Cleavage and C-C Bond
      Formation? A Theoretical Study.
AB  - Ni-catalyzed cross-coupling between aryl alkyl ethers (ArOR) and Grignard
      reagents (RMgBr), known since 1979, proceeds under mild conditions in many cases.
      Although the reaction routes of various synthetic protocols involving transition
      metal-catalyzed C-O bond activation have been elucidated, the mechanism of this
      etheric Kumada-Tamao-Curriu reaction remains enigmatic. This is because oxidative
      addition of inert etheric C-O to Ni(0) is thermodynamically and kinetically
      unfavorable, making it hard to explain the observed high reactivity of ether
      toward Ni catalysts. In this work, we used DFT calculations to identify a
      plausible reaction pathway by the Ni(0)-ate complex, which enables smooth C-O
      bond cleavage and R-group transfer with reasonable activation barriers; this
      mechanism also accounts for the ineffectiveness of Pd catalysts. These results
      throw new light on both C-O activation and cross-coupling, and should be valuable
      for further rational development of the methodologies.

PMID- 26294324
TI  - Comparison of MRI and high-resolution transvaginal sonography for the local
      staging of cervical cancer.
AB  - PURPOSE: The aim of this prospective study was to compare the diagnostic accuracy
      of transvaginal sonography (TVS) with that of MRI in the local staging of
      cervical cancer. METHODS: All consecutive patients diagnosed with invasive
      carcinoma of the cervix over a 3-year period underwent MRI of the pelvis and TVS
      according to a standardized protocol. RESULTS: In total, 46 patients were
      recruited to the study. We found a strong correlation between MRI and TVS in the
      assessment of tumor volume in both early-stage and advanced-stage disease (p <
      0.0001). Both MRI and TVS had a sensitivity of 80%, a specificity of 50%, and a
      diagnostic accuracy of 63.6% for the detection of stromal invasion in early-stage
      disease. For the detection of parametrial invasion, we found sensitivity rates of
      40% for MRI and 86% for TVS; specificity rates of 78.8% for MRI and 20% for TVS;
      and diagnostic accuracy rates of 89% for MRI and 78.7% for TVS. A matched-sample
      analysis revealed that there was no statistically significant difference between
      MRI and TVS in the assessment of stromal or parametrial invasion (p = 0.06).
      CONCLUSIONS: TVS performed by a dedicated gynecologic radiologist is a feasible
      and economic imaging modality with a diagnostic accuracy comparable to that of
      MRI. It may be used as an adjunct to MRI for the local staging of invasive
      cervical cancer or to allow for rapid and confident triage of patients into
      operative and nonoperative categories for management in the gynecologic
      outpatient setting.

PMID- 26294326
TI  - HIV prevention among street-based sex workers (SSWs) in Chongqing, China:
      interviews with SSWs, clients and healthcare providers.
AB  - Street-based female sex workers (SSWs) are subjected to a relatively high risk of
      HIV transmission, even higher than establishment-based female sex workers in
      China. However, very few HIV intervention programmes have targeted this
      particular group to date. Based in Southwest China, this study aims to identify
      perceived barriers, demands and suggestions on HIV prevention from the
      perspectives of SSWs, clients and healthcare providers in Chongqing. Face-to
      face, in-depth interviews were conducted in July 2008 with 23 participants. They
      were recruited by purposive, convenience sampling and included 12 SSWs, 5 male
      clients, 4 government healthcare providers and 2 outreach workers from a
      community-based non-governmental organisation. Thematic analysis was used. SSWs
      were largely rural-to-urban migrants with a low socioeconomic status. Most of
      their clients shared a similar background. Both SSWs and their clients
      demonstrated a low awareness of HIV infection and a lack of understanding of
      effective preventive strategies. Financial hardships, lack of family support,
      fear of police arrest and stigma in relation to sex work were identified as SSWs'
      major barriers for accessing healthcare services. Both SSWs and their clients
      indicated an urgent demand for accessing adequate HIV prevention and care
      programmes. On the other hand, government organisations trying to provide
      services to this group have also encountered obstacles, specifically their
      limited ability to establish mutual trust. Programmes provided by community-based
      non-governmental organisation, however, were perceived to be more attractive. In
      conclusion, there remains a substantial gap between the need of adequate HIV
      prevention services for SSWs and their clients and what is currently available.
      Strengthening inter-sectoral collaboration, providing specifically tailored
      health services, actively involving SSW peers and their clients, and reducing
      stigma in the society are keys to meet this urgent demand by SSWs in China.

PMID- 26294327
TI  - Precipitated and chemically-crosslinked laccase over polyaniline nanofiber for
      high performance phenol sensing.
AB  - The present study aims at fabricating a laccase (LAC) based amperometric
      biosensor for detection of phenolic compounds. LAC was immobilized into the
      porous matrix of polyaniline nanofibers (PANFs) in a three-step process,
      consisting of enzyme adsorption, precipitation, and crosslinking (EAPC).
      Immobilized LAC on PANF in the form of EAPC was highly active and stable when
      compared to control samples of 'enzyme adsorption (EA)' and 'enzyme adsorption
      and crosslinking (EAC)' samples. For example, the activity of EAPC was 19.7 and
      15.1 times higher than those of EA and EAC per unit weight of PANF, respectively.
      After 6days at room temperature, EAPC maintained 100% of its initial activity,
      while EA and EAC retained only 7.7% and 11% of their initial activities,
      respectively. When the samples were subjected to the heat treatment at 60 degrees
      C over 3h, EAPC maintained 74% of its initial activity, while EA and EAC retained
      around 1% of their initial activities, respectively. To demonstrate the feasible
      application of EAPC in biosensors, the enzyme electrodes were prepared and used
      for detection of phenolic compounds, which are environmentally hazardous
      chemicals. The sensitivities of biosensors with EA, EAC, and EAPC were 20.3+/
      5.9, 26.6+/-5.4 and 518+/-11MUAmM(-1)cm(-2), respectively. At 50 degrees C for
      5h, EAPC electrode maintained 80% of its initial sensitivity, while EA and EAC
      electrode showed 0% and 19% of their initial sensitivities, respectively. Thus,
      LAC-based biosensor using EAPC protocol with PANFs showed a great promise for
      developing a highly sensitive and stable biosensor for detection of phenolic
      compounds. 

PMID- 26294325
TI  - Transcriptomic analysis of pancreatic cancer cells in response to metformin and
      aspirin: an implication of synergy.
AB  - Metformin and aspirin have been studied extensively as cancer preventative and
      therapeutic agents. However, the underlying molecular mechanisms for the
      inhibitory effects of pancreatic cancer development remain undefined. To gain
      further insight into their biological function in pancreatic cancer, we conducted
      a transcriptomic analysis using RNA sequencing to assess the differential gene
      expression induced by metformin (5 mM) and aspirin (2 mM), alone or in
      combination, after treatment of PANC-1 cells for 48 hours. Compared to an
      untreated control, metformin down-regulated 58 genes and up-regulated 91 genes,
      aspirin down-regulated 12 genes only, while metformin plus aspirin down-regulated
      656 genes and up-regulated 449 genes (fold-change > 2, P < 10(-5)). Of the top 10
      genes (fold-change > 10, P < 10(-10)) regulated by metformin plus aspirin,
      PCDH18, CCL2, RASL11A, FAM111B and BMP5 were down-regulated >= 20-fold, while
      NGFR, NPTX1, C7orf57, MRPL23AS1 and UNC5B were up-regulated >= 10-fold. Ingenuity
      Pathway Analysis (IPA) revealed that the pathways, "cholesterol biosynthesis",
      "cell cycle: G1/S checkpoint regulation", and "axonal guidance signaling" were
      the most statistically significant pathways modulated by metformin plus aspirin.
      Although the results need further functional validation, these data provide the
      first evidence for the synergistic action between metformin and aspirin in
      modulating the transcriptional profile of pancreatic cancer cells. 

PMID- 26294329
TI  - A comparative study of matched pair designs with two binary endpoints.
AB  - We study matched pair designs with two binary endpoints under three different
      approaches. Power approximation and sample size calculation are derived under
      these situations and facilitated by R programs. An adaptive design with sample
      size re-estimation is also presented. Through extensive simulations, we provide
      general guidelines for practitioners to choose the best approach according to the
      ranges of the interested parameters in the sense of feasibility and robustness.
      Application to a cancer chemotherapy trial is illustrated.

PMID- 26294328
TI  - Predicting Short-Term Remembering as Boundedly Optimal Strategy Choice.
AB  - It is known that, on average, people adapt their choice of memory strategy to the
      subjective utility of interaction. What is not known is whether an individual's
      choices are boundedly optimal. Two experiments are reported that test the
      hypothesis that an individual's decisions about the distribution of remembering
      between internal and external resources are boundedly optimal where optimality is
      defined relative to experience, cognitive constraints, and reward. The theory
      makes predictions that are tested against data, not fitted to it. The experiments
      use a no-choice/choice utility learning paradigm where the no-choice phase is
      used to elicit a profile of each participant's performance across the strategy
      space and the choice phase is used to test predicted choices within this space.
      They show that the majority of individuals select strategies that are boundedly
      optimal. Further, individual differences in what people choose to do are
      successfully predicted by the analysis. Two issues are discussed: (a) the
      performance of the minority of participants who did not find boundedly optimal
      adaptations, and (b) the possibility that individuals anticipate what, with
      practice, will become a bounded optimal strategy, rather than what is boundedly
      optimal during training.

PMID- 26294330
TI  - Applications of temporal kernel canonical correlation analysis in adherence
      studies.
AB  - Adherence to medication is often measured as a continuous outcome but analyzed as
      a dichotomous outcome due to lack of appropriate tools. In this paper, we
      illustrate the use of the temporal kernel canonical correlation analysis (tkCCA)
      as a method to analyze adherence measurements and symptom levels on a continuous
      scale. The tkCCA is a novel method developed for studying the relationship
      between neural signals and hemodynamic response detected by functional MRI during
      spontaneous activity. Although the tkCCA is a powerful tool, it has not been
      utilized outside the application that it was originally developed for. In this
      paper, we simulate time series of symptoms and adherence levels for patients with
      a hypothetical brain disorder and show how the tkCCA can be used to understand
      the relationship between them. We also examine, via simulations, the behavior of
      the tkCCA under various missing value mechanisms and imputation methods. Finally,
      we apply the tkCCA to a real data example of psychotic symptoms and adherence
      levels obtained from a study based on subjects with a first episode of
      schizophrenia, schizophreniform or schizoaffective disorder.

PMID- 26294331
TI  - The blood pressure effect and related plasma levels of flavan-3-ols in
      spontaneously hypertensive rats.
AB  - We studied the short-term antihypertensive effect of flavan-3-ols (-)
      epicatechin, (+)-catechin and (-)-catechin, in spontaneously hypertensive rats
      (SHR). Plasma metabolites and the corresponding plasma antioxidant capacity were
      determined. All the assayed flavan-3-ols decreased systolic blood pressure (SBP)
      in SHR. Their antihypertensive effects were less pronounced than that of
      Captopril (50 mg kg(-1)) and were not shown in normotensive Wistar-Kyoto rats. 6
      mg kg(-1) (-)-epicatechin caused the maximum decrease in SBP. The maximum effects
      of the catechin monomers were observed post-administration of 0.5 mg kg(-1) of
      flavan-3-ols, (-)-catechin being the least effective among the three assayed
      compounds. Glucuronide and methyl glucuronide metabolites were obtained in the
      flavan-3-ol treated SHR, but it was not possible to relate the antihypertensive
      effect of the assayed flavan-3-ols with a concrete plasma metabolite or with
      their antioxidant effect. In conclusion, the studied flavan-3-ols could be
      responsible for the antihypertensive effect of cocoa products. 

PMID- 26294332
TI  - Evaluating frequency of PML-RARA mutations and conferring resistance to arsenic
      trioxide-based therapy in relapsed acute promyelocytic leukemia patients.
AB  - The aim of the study is to better understand the mechanism of relapse and
      acquired clinical resistance to arsenic trioxide (ATO) and/or all-trans retinoic
      acid (ATRA). Thirty relapsed acute promyelocytic leukemia (APL) patients were
      followed. Fifteen patients experienced two or more relapses; nine patients had
      clinical resistance to ATO-based therapy. The frequency and clinical significance
      of promyelocytic leukemia (PML)-retinoic acid receptor alpha (RARA) mutational
      status using Sanger sequencing were evaluated. Overall, eight different types of
      mutations in the RARA region (V218D, R272Q, T278A, T291I, N299D, R294W, A300G,
      and L220_F228delinsP) were identified in 11 patients. Eight missense mutations
      (L211P, C213R, S214L, A216V, L217F, D219H, S221G, and D241G) were found in the
      PML portion of PML-RARA in 14 patients, with A216V as the predominant mutation.
      Eight patients were found to harbor both PML and RARA mutations over the course
      of the disease. The PML-region mutations were associated with response to ATO
      based therapy (P < 0.0001), number of relapses (P = 0.001), and early relapse (P
      = 0.013). Notably, one case sampled at nine different time points showed
      alternating clonal dominance over the course of treatment. This study
      demonstrated frequent mutations of PML-RARA and supported a clonal selection
      model in relation to APL relapse and ATO resistance. 

PMID- 26294333
TI  - Thou shalt not tweet unprofessionally: an appreciative inquiry into the
      professional use of social media.
AB  - BACKGROUND: Social media may blur the line between socialisation and professional
      use. Traditional views on medical professionalism focus on limiting motives and
      behaviours to avoid situations that may compromise care. It is not surprising
      that social media are perceived as a threat to professionalism. OBJECTIVE: To
      develop evidence for the professional use of social media in medicine. METHODS: A
      qualitative framework was used based on an appreciative inquiry approach to
      gather perceptions and experiences of 31 participants at the 2014 Social Media
      Summit. RESULTS: The main benefits of social media were the widening of networks,
      access to expertise from peers and other health professionals, the provision of
      emotional support and the ability to combat feelings of isolation. CONCLUSIONS:
      Appreciative inquiry is a tool that can develop the positive practices of
      organisations and individuals. Our results provide evidence for the professional
      use of social media that may contribute to guidelines to help individuals realise
      benefits and avoid harms.

PMID- 26294334
TI  - Management of Severe Insulin Resistance in Patients with Type 1 Diabetes.
AB  - Managing severe insulin resistance (IR) in patients with type 1 diabetes (T1DM)
      can be challenging for both clinicians and patients. As average weight for
      patients with T1DM has increased in recent decades, IR in this population has
      become more widespread. Currently, almost 50 % of patients with T1DM are
      overweight or obese. While intensive insulin therapy is associated with reduction
      in complications, aggressive treatment can lead to weight gain. With increasing
      weight, insulin can become less effective to control glycemia, resulting in
      higher insulin doses and hence more weight gain. Novel strategies to break this
      vicious cycle are needed. This review will investigate current research on
      insulin formulations, lifestyle modification, adjunct therapies, and surgery that
      may help better manage patients with T1DM and IR. 

PMID- 26294337
TI  - A comparison of drug eluting stent biocompatibility between third generation
      NOBORI biolimus A9-eluting stent and second generation XIENCE V everolimus
      eluting stent in a porcine coronary artery model.
AB  - BACKGROUND AND PURPOSE: NOBORI biolimus A9-eluting stent (BES) is the third
      generation drug eluting stent (DES) with only abluminal biodegradable polymer.
      Recent clinical trials have indicated that the BES is non-inferior to the XIENCE
      V everolimus-eluting stent (EES). Meanwhile, potential superiority of
      biodegradable polymer BES over current generation DES has not been addressed. The
      aim of this preclinical study was to assess and compare the biocompatibility of
      both BES and EES in porcine coronary arteries. METHODS AND MATERIALS: BES with
      length of 24-mm (n=9) and EES with length of 23-mm (n=9) were both implanted in
      porcine coronary arteries. At 28 days endothelium-dependent vasomotion was
      assessed by acetylcholine (Ach) and subsequently measurements of endothelial
      superoxide production, histological evaluations and microarray gene analyses were
      performed. RESULTS: Angiographic and histological in-stent stenoses were
      significantly suppressed in BES compared with EES. Histopathological assessment
      showed lower inflammatory score as well as fibrin and injury scores in BES as
      compared with EES. On the contrary, paradoxical vasoconstriction to Ach was
      frequently observed in EES-treated vessels compared with BES-treated vessels.
      Additionally, gene expressions of inflammatory cytokines and chemokines were
      upregulated in vessels treated with EES compared with BES in microarray pathway
      specific analyses. CONCLUSIONS: Implantation of BES revealed less inflammation
      and foreign-body immunoreaction than EES, suggesting more enhanced
      biocompatibility of BES compared with EES at 28 days in porcine coronary
      arteries.

PMID- 26294335
TI  - Beta Cell Function and the Nutritional State: Dietary Factors that Influence
      Insulin Secretion.
AB  - Approximately 366 million people worldwide have been diagnosed with type-2
      diabetes (T2D). Chronic insulin resistance, decreased functional beta-cell mass,
      and elevated blood glucose are defining characteristics of T2D. Great advances
      have been made in understanding the pathogenesis of T2D with respect to the
      effects of dietary macronutrient composition and energy intake on beta-cell
      physiology and glucose homeostasis. It has been further established that obesity
      is a leading pathogenic factor for developing insulin resistance. However,
      insulin resistance may not progress to T2D unless beta-cells are unable to secret
      an adequate amount of insulin to compensate for decreased insulin sensitivity.
      Therefore, pancreatic beta-cell dysfunction plays an important role in the
      development of overt diabetes. This paper reviews recent research findings on the
      effects of several micronutrients (zinc, vitamin D, iron, vitamin A), leucine,
      and the phytochemical, genistein on pancreatic beta-cell physiology with emphasis
      on their effects on insulin secretion, specifically in the context of T2D. 

PMID- 26294336
TI  - Novel Therapies in Development for Diabetic Macular Edema.
AB  - Diabetic macular edema (DME) secondary to diabetic retinopathy (DR) is a major
      cause for functional visual loss in the developed world. Laser photocoagulation
      has been used for decades in the treatment of DME. However, the advent of anti
      vascular endothelial growth factor (anti-VEGF) has revolutionized the treatment
      of DME. Three important anti-VEGF agents whose efficacy has been well established
      via phase III clinical trials include ranibizumab, bevacizumab, and aflibercept.
      However, even in the era of anti-VEGF therapies, there are some challenges that
      retina specialists have to confront in managing patients with DME. These include
      the need for frequent treatment and an unpredictable response to therapy. There
      is evidence to suggest that pathways other than the VEGF pathway may be playing a
      role in the development of DME. Thus, extensive research is focused on
      development of novel agents that target these pathways. This review focuses on
      novel therapeutic agents in development, which may be used as a monotherapy or in
      combination with anti-VEGF agents, for the management of DME in the future. 

PMID- 26294338
TI  - Laparoscopic pancreatoduodenectomy does not completely mitigate increased
      perioperative risks in elderly patients.
AB  - BACKGROUND: Elderly patients undergoing open pancreatoduodenectomy (OPD) are at
      increased risk for surgical morbidity and mortality. Whether totally laparoscopic
      pancreatoduodenectomy (TLPD) mitigates these risks has not been evaluated.
      METHODS: A retrospective review of outcomes in patients submitted to
      pancreatoduodenectomy during 2007-2014 was conducted (n = 860). Outcomes in
      elderly patients (aged >=70 years) were compared with those in non-elderly
      patients with respect to risk-adjusted postoperative morbidity and mortality.
      Differences in outcomes between patients submitted to OPD and TLPD, respectively,
      were evaluated in the elderly subgroup. RESULTS: In elderly patients, the
      incidences of cardiac events (odds ratio [OR] 3.21, P < 0.001), respiratory
      events (OR 1.68, P = 0.04), delayed gastric emptying (DGE) (OR 1.73, P = 0.003),
      increased length of stay (LoS, 1 additional day) (P < 0.001), discharge
      disposition other than home (OR 8.14, P < 0.001) and blood transfusion (OR 1.48,
      P = 0.05) were greater than in non-elderly patients. Morbidity and mortality did
      not differ between the OPD and TLPD subgroups of elderly patients. In elderly
      patients, OPD was associated with increased DGE (OR 1.80, P = 0.03), LoS (1
      additional day; P < 0.001) and blood transfusion (OR 2.89, P < 0.001) compared
      with TLPD. CONCLUSIONS: Elderly patients undergoing TLPD experience rates of
      mortality, morbidity and cardiorespiratory events similar to those in patients
      submitted to OPD. In elderly patients, TLPD offers benefits by decreasing DGE,
      LoS and blood transfusion requirements.

PMID- 26294339
TI  - Mild-temperature thermochemical pretreatment of green macroalgal biomass: Effects
      on solubilization, methanation, and microbial community structure.
AB  - The effects of mild-temperature thermochemical pretreatments with HCl or NaOH on
      the solubilization and biomethanation of Ulva biomass were assessed. Within the
      explored region (0-0.2M HCl/NaOH, 60-90 degrees C), both methods were effective
      for solubilization (about 2-fold increase in the proportion of soluble organics),
      particularly under high-temperature and high-chemical-dose conditions. However,
      increased solubilization was not translated into enhanced biogas production for
      both methods. Response surface analysis statistically revealed that HCl or NaOH
      addition enhances the solubilization degree while adversely affects the
      methanation. The thermal-only treatment at the upper-limit temperature (90
      degrees C) was estimated to maximize the biogas production for both methods,
      suggesting limited potential of HCl/NaOH treatment for enhanced Ulva
      biomethanation. Compared to HCl, NaOH had much stronger positive and negative
      effects on the solubilization and methanation, respectively. Methanosaeta was
      likely the dominant methanogen group in all trials. Bacterial community structure
      varied among the trials according primarily to HCl/NaOH addition. 

PMID- 26294340
TI  - Adequacy of peripheral blood stem cell mobilization in patients with relapsed B
      cell non-Hodgkin lymphoma treated with bendamustine.

PMID- 26294341
TI  - Can Clinical Assessment of Locomotive Body Function Explain Gross Motor
      Environmental Performance in Cerebral Palsy?
AB  - Gross Motor Function Classification System has discriminative purposes but does
      not assess short-term therapy goals. Locomotion Stages (LS) classify postural
      body functions and independent activity components. Assessing the relation
      between Gross Motor Function Classification System level and Locomotion Stages
      will make us understand if clinical assessment can explain and predict motor
      environmental performance in cerebral palsy. A total of 462 children were
      assessed with both scales. High reliability and strong negative correlation (
      0.908) for Gross Motor Function Classification System and Locomotion Stages at
      any age was found. Sensitivity was 83%, and specificity and positive predictive
      value were 100% within the same age range. Regression analysis showed detailed
      probabilities for the realization of the Gross Motor Function Classification
      System depending on the Locomotion Stages and the age group. Postural body
      function measure with Locomotion Stages is reliable, sensitive, and specific for
      gross motor function and able to predict environmental performance. 

PMID- 26294344
TI  - The Untapped Potential of Tunneled Pleural Catheters.
AB  - BACKGROUND: Tunneled pleural catheters (TPCs) are routinely used for outpatient
      drainage of malignant pleural effusions, although use in recurrent pleural
      effusions resulting from nonmalignant conditions requires further evaluation. We
      hypothesized that TPCs could decrease inpatient admission rates for exacerbations
      of nonmalignant pleural effusions. METHODS: A retrospective chart review was done
      of patients with TPCs inserted for recurrent nonmalignant pleural effusions.
      Patients were set up with home care nursing support and catheter draining two to
      three times per week and were then followed on an outpatient basis until
      spontaneous pleurodesis and catheter removal. Data collection included
      demographics, comorbidities, and hospital admission rates relative to TPC
      placement as well as removal. RESULTS: Thirty-seven patients with recurrent,
      nonmalignant pleural effusions were enrolled (17 female and 20 male patients).
      Patients had comorbid conditions including hypertension (86%), chronic kidney
      disease (59%), congestive heart failure (67%), liver disease (11%), and
      malnutrition (22%), and most patients (89%) had multiples of these conditions.
      Total admissions for pleural effusion exacerbations decreased from 59 to 15 in
      the 1 year before and after TPC placement and from 42 to 6 in the respective 3
      month periods (p < 0.0001). Six of the 37 patients still had TPCs in place; for
      the remaining 31 patients, admissions decreased from 60 to 9 in the 1-year
      periods before and after TPC removal and from 33 to 2 in the respective 3-month
      periods (p < 0.0001); no patients required subsequent pleural interventions.
      CONCLUSIONS: The study results support TPC placement in recurrent nonmalignant
      pleural effusions refractory to medical management as an effective and plausible
      management option.

PMID- 26294342
TI  - Role of endothelial TRPV4 channels in vascular actions of the endocannabinoid, 2
      arachidonoylglycerol.
AB  - BACKGROUND AND PURPOSE: Metabolites of the endocannabinoid, 2
      arachidonoylglycerol (2-AG) have been postulated to act as endogenous activators
      of TRPV4, a Ca(2+) -permeable cation channel that plays a critical role in
      endothelium-dependent relaxation. However, it is unclear if TRPV4 contributes to
      the vascular actions of 2-AG. EXPERIMENTAL APPROACH: Isometric tension recording
      of rat small mesenteric arteries and aortae were used to assess the effect of 2
      AG and the synthetic TRPV4 activator, GSK1016790A (GSK) on vascular reactivity.
      Changes in intracellular Ca(2+) concentration and single-channel currents were
      measured in TRPV4-expressing human coronary endothelial cells. KEY RESULTS: In
      mesenteric arteries, endothelium-dependent relaxation to both 2-AG and GSK was
      attenuated by structurally distinct TRPV4 antagonists, HC067047, RN1734 and
      ruthenium red. The responses were inhibited by KCa inhibitors (apamin +
      charybdotoxin) and a gap junction inhibitor (18alpha-glycyrrhetinic acid). In
      contrast to GSK, 2-AG elicited considerable relaxation independently of the
      endothelium or TRPV4. Inhibition of 2-AG metabolism via monoacylglycerol lipase
      and COX (by MAFP and indomethacin) caused potentiation, while cytochrome P450 and
      lipoxygenase inhibitors had no effect on 2-AG relaxation. In coronary endothelial
      cells, 2-AG (with and without MAFP) induced HC067047-sensitive increases in
      intracellular Ca(2+) concentration. 2-AG also increased TRPV4 channel opening in
      inside-out patches. However, in aortae, GSK induced a relaxation sensitive to
      HC067047 and ruthenium red, whereas 2-AG induced contractions. CONCLUSIONS AND
      IMPLICATIONS: These data suggest that 2-AG can directly activate endothelial
      TRPV4, which partly contributes to the relaxant response to 2-AG. However, the
      functional role of TRPV4 is highly dependent on the vascular region.

PMID- 26294343
TI  - Ultrafast electron dynamics at the Dirac node of the topological insulator
      Sb2Te3.
AB  - Topological insulators (TIs) are a new quantum state of matter. Their surfaces
      and interfaces act as a topological boundary to generate massless Dirac fermions
      with spin-helical textures. Investigation of fermion dynamics near the Dirac
      point (DP) is crucial for the future development of spintronic devices
      incorporating topological insulators. However, research so far has been
      unsatisfactory because of a substantial overlap with the bulk valence band and a
      lack of a completely unoccupied DP. Here, we explore the surface Dirac fermion
      dynamics in the TI Sb2Te3 by time- and angle-resolved photoemission spectroscopy
      (TrARPES). Sb2Te3 has an in-gap DP located completely above the Fermi energy
      (EF). The excited electrons in the upper Dirac cone stay longer than those below
      the DP to form an inverted population. This was attributed to a reduced density
      of states (DOS) near the DP. 

PMID- 26294345
TI  - Comparison of 3-Year Outcomes for Coronary Artery Bypass Graft Surgery and Drug
      Eluting Stents: Does Sex Matter?
AB  - BACKGROUND: Several randomized controlled trials and observational studies have
      compared outcomes for coronary artery bypass graft (CABG) surgery and drug
      eluting stents (DES), but these studies have not thoroughly investigated the
      relative difference in outcomes by sex. We aimed to compare 3-year outcomes
      (mortality, mortality/myocardial infarction/stroke, and repeat revascularization)
      for CABG surgery and percutaneous coronary interventions with DES by sex.
      METHODS: A total of 4,532 women (2,266 pairs of CABG and DES patients) and 11,768
      men (5,884 pairs) were propensity matched separately using multiple patient risk
      factors and were compared with respect to 3-year outcomes. RESULTS: Both women
      and men receiving DES had significantly higher mortality rates (adjusted hazard
      ratio, 1.28; 95% confidence interval, 1.06 to 1.54 and adjusted hazard ratio,
      1.22; 95% confidence interval, 1.06 to 1.41, respectively) and myocardial
      infarction/mortality/stroke rates (adjusted hazard ratio, 1.40; 95% confidence
      interval, 1.19 to 1.64 and adjusted hazard ratio, 1.36; 95% confidence interval,
      1.20 to 1.54, respectively) with DES. The advantage for CABG surgery was also
      present for several preselected patient subgroups. Men had consistently lower
      adverse outcome rates than women for both procedures. For example, the mortality
      rates for CABG and DES for men were 8.0% and 9.1%, compared with respective rates
      of 11.8% and 13.7% for women. CONCLUSIONS: For women, the advantage of CABG
      surgery over DES is very similar to what was found for men, and this advantage
      persisted for patients with and without high-risk characteristics.

PMID- 26294346
TI  - Risky Business: Taking the Stigma Out of High-Risk Donation in Lung
      Transplantation.
AB  - BACKGROUND: Outcomes data for high-risk donors (HRD) for transplantation are
      limited. We sought to elucidate the outcomes of lung transplant (LTx) recipients
      who received HRDs. METHODS: We retrospectively reviewed the United Network for
      Organ Sharing (UNOS) registry from January 2005 to June 2013 to identify patients
      undergoing LTx. The Student t test and chi(2) test were used to identify
      differences in outcomes. A Cox proportional hazard model was developed to
      identify independent predictors of outcomes for HRD recipients. RESULTS: We
      identified 12,737 patients who underwent LTx. A total of 999 (7.8%) recipients
      received allografts from HRDs. Recipients in both the HRD and the non-HRD (NHRD)
      groups were similar. The HRDs had significantly higher rates of negative social
      behaviors and were likely to be thin young males who had died traumatically.
      Survival analysis demonstrated no survival benefit for patients receiving
      allografts from NHRDs (p = 0.63). Interestingly, HRDs did not have significantly
      higher viral loads, including hepatitis C virus (HCV) antibody, hepatitis B core
      antibody (HBcV), or hepatitis B surface antigen. When controlling for age, sex,
      and lung allocation score of the recipient, HRD status was not significantly
      detrimental to survival. CONCLUSIONS: Recipients receiving allografts from HRDs
      had at least equivalent survival to NHRD recipients. Our study supports the use
      of high-risk donation given limited resources. Centers interested in using these
      donors should educate prospective recipients willing to consider this option.

PMID- 26294347
TI  - Endobronchial Valves in the Treatment of Persistent Air Leaks.
AB  - BACKGROUND: Endobronchial valves (EBVs) are a useful adjunct in the management
      algorithm of patients with persistent pulmonary air leaks. They are increasingly
      used in the management of postsurgical parenchymal air leaks and carry a
      humanitarian use device exemption for this purpose. We report our experience with
      EBVs in the management of patients with bronchopleural fistula secondary to
      postsurgical intervention and spontaneous pneumothorax from medical
      comorbidities. METHODS: An institutional review board-approved retrospective
      review was conducted of our single-center EBV experience. Patients were
      categorized as postsurgical versus medical. Data collected included demographic
      characteristics, indication for and number of valves placed, and chest tube
      duration before and after valve placement to evaluate overall resolution of air
      leak. Success was defined as resolution of air leak. RESULTS: A total of 14 valve
      placement procedures were performed. Mean age was 60 years and 10 patients were
      men. Eight represented prolonged leaks secondary to postsurgical complications
      and six were secondary to medical comorbidities. Indications for placement of
      valves in medical patients included persistent leak secondary to lung biopsy,
      ruptured bleb disease, and pneumothorax after cardiopulmonary resuscitation.
      Postsurgical indications included leaks secondary to lung biopsy, lobectomy, and
      ruptured bleb disease. A median of two valves were placed per procedure. A
      postprocedure median length of stay of 14.5 days was observed in the surgical
      group compared with 15 days in the medical group. Overall success rate was 57%
      (surgical group, 62.5%; medical group, 50%). CONCLUSIONS: EBVs are a useful
      adjunct in the management of persistent pulmonary air leaks, particularly when
      conventional interventions are contraindicated or not ideal. EBVs are well
      tolerated in the critically ill, have few known complications, are removable, and
      do not preclude future surgical intervention. Future studies should evaluate EBV
      efficacy versus the natural course of persistent pulmonary air leaks and their
      impact on cost and length of stay.

PMID- 26294349
TI  - Sudden Death Due To Acute Cocaine Toxicity-Excited Delirium in a Body Packer.
AB  - Excited delirium denotes a life-threatening medical condition characterized by
      the acute onset of agitated and violent behavior that often results in a sudden
      and unexplained death. Cocaine-induced excited delirium refers to fatal cocaine
      intoxication with the following symptoms occurring sequentially: hyperthermia,
      delirium with agitation, respiratory arrest, and death. We present a case of
      cocaine-induced excited delirium in a cocaine "body packer" or a "mule",
      specifically an individual who attempts to smuggle cocaine within the body.
      Investigators at the scene initially suspected homicide due to the victim's sharp
      and blunt force injuries. Three rubber packets containing cocaine were removed
      from the victim's rectum. Blood toxicological analysis revealed an alcohol
      concentration of 0.016 g/100 and cocaine >1 mg/L. The forensic pathologist should
      consider cocaine-induced excited delirium when an individual exhibits aggressive
      behavior, unexpected strength, and resistance to pain who dies suddenly. Further
      analysis should be performed during the scene investigation and autopsy for
      evidence of body packing.

PMID- 26294348
TI  - A Compact DNA Cube with Side Length 10 nm.
AB  - A small and compact DNA cube with zeptoliter volume is constructed by means of a
      generalized DNA brick concept using short synthetic oligonucleotides with varying
      lengths. By mimicking design principles from the DNA origami technique, the DNA
      cube offers higher stability and assembly yields compared to other approaches.
      Its potential application as nanoscale fluorescent probe is demonstrated using
      super-resolution imaging. 

PMID- 26294350
TI  - Subtyping of the Legionella pneumophila "Ulm" outbreak strain using the CRISPR
      Cas system.
AB  - In 2009/2010 an outbreak of Legionnaires' disease with 64 cases including four
      fatalities took place in the city of Ulm/Neu-Ulm in Germany. L. pneumophila
      serogroup 1, mAb type Knoxville, sequence type (ST) 62 was identified as the
      epidemic strain. This strain was isolated from eight patients and from a cooling
      tower in the city of Ulm. Based on whole genome sequencing data from one patient
      strain, we identified an Lvh type IV secretion system containing a CRISPR-Cas
      system. The CRISPR sequence contains 38 spacer DNA sequences. We used these
      variable DNA spacers to further subtype the outbreak strain as well as six
      epidemiologically unrelated strains of CRISPR-Cas positive ST62 strains isolated
      at various regions in Germany. The first 12 spacer DNAs of eight patient isolates
      and three environmental isolates from the suspected source of infection were
      analyzed and found to be identical. Spacer DNAs were identified in further six
      epidemiologically unrelated patient isolates of L. pneumophila of ST62 in
      addition to the 12 "core" spacers. The presence of new spacer DNAs at the 5' site
      downstream of the first repeat indicates that these CRISPR-Cas systems seem to be
      functional. PCR analysis revealed that not all L. pneumophila sg1 ST62 strains
      investigated exhibited a CRISPR-Cas system. In addition, we could demonstrate
      that the CRISPR-Cas system is localized on a genomic island (LpuGI-Lvh) which can
      be excised from the chromosome and therefore may be transferable horizontally to
      other L. pneumophila strains. 

PMID- 26294351
TI  - Hyperinsulinism and polycystic ovary syndrome (PCOS): role of insulin clearance.
AB  - PURPOSE: Insulin resistance and compensatory hyperinsulinism are the predominant
      metabolic defects in polycystic ovary syndrome (PCOS). However, hyperinsulinism,
      as well as being compensatory, can also express a condition of reduced insulin
      clearance. Our aim was to evaluate the differences in insulin action and
      metabolism between women with PCOS (with normal glucose tolerance) and age- and
      BMI-matched women with prediabetes (without hyperandrogenism and ovulatory
      disorders). METHODS: 22 women with PCOS and 21 age/BMI-matched women with
      prediabetes were subjected to a Hyperinsulinemic-euglycemic clamp and an Oral
      Glucose tolerance Test (OGTT). Insulin sensitivity was assessed by the glucose
      infusion rate during clamp (M value); insulin secretion by Insulinogenic index,
      Oral Disposition Index (DIo) and AUC(2h-insulin) during OGTT; and insulin
      clearance by the metabolic clearance rate of insulin (MCRI) during clamp.
      RESULTS: Women with PCOS showed significantly higher levels of AUC(2h-insulin) (p
      < 0.011), Insulinogenic Index (p < 0.001), DIo (p = 0.002) and significantly
      lower levels of AUC(2h-glucos)e (p = 0.001). No difference was found between the
      two groups regarding insulin sensitivity (M value). Lower levels of MCRI were
      found in women with PCOS [420 (IQR 227-588) vs. 743 (IQR 597-888) ml m(-2) min(
      1): p < 0.001]. Furthermore, in the PCOS group, a strong independent inverse
      correlation was only observed between MCRI and AUC(2h-insulin) (PCOS: beta:
      0.878; p < 0.001; Prediabetes: beta:-0.501; p = 0.019). CONCLUSIONS: Our study
      suggests that in normoglycemic women with PCOS there is peripheral insulin
      sensitivity similar to that of women with prediabetes. What sets PCOS apart is
      the hyperinsulinism, today still simplistically defined "compensatory"; actually
      this is mainly related to decreased insulin clearance whose specific causes and
      dynamics have yet to be clarified.

PMID- 26294352
TI  - Association of human telomerase reverse transcriptase gene polymorphisms, serum
      levels, and telomere length with renal cell carcinoma risk and pathology.
AB  - Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of the
      human telomerase and plays a key role in telomere restitution and gene
      regulation. Evidence suggests that hTERT is linked with the risk and progression
      of several malignancies, but there are no comprehensive data in renal cell
      carcinoma (RCC). In this case-control study, we assessed seven polymorphic hTERT
      gene variants (MNS16A, rs2736100, rs2736098, rs7726159, rs2853677, rs13172201,
      and rs10069690), hTERT serum levels, and the telomere length of 663 individuals,
      including 243 with clear cell RCC and 420 age- and gender-matched healthy
      controls. The SL and SS genotypes of MNS16A were associated with a decreased risk
      for RCC on the multivariable logistic regression analysis (SL-OR 0.72, SS-OR
      0.37, P < 0.001). The GG genotype of rs2736098 was associated with a decreased
      risk for RCC compared with AA (OR 0.18, P < 0.001). Both telomere length and
      hTERT serum levels increased with every G allele in rs2736098 (P = 0.008).
      Pretherapeutic hTERT serum levels were higher in patients with advanced tumor
      stages (P = 0.037) and distant metastases (P = 0.006). Rs2736100, rs7726159,
      rs2853677, rs13172201, and rs10069690 were not linked with RCC risk, and none of
      the polymorphisms was associated with RCC pathology. In conclusion, the
      polymorphic number of tandem repeats in hTERT (MNS16A) and rs2736098 may be
      linked with the risk for RCC. Rs2736098 may have an important role in telomere
      length restitution and serum hTERT levels may represent a novel biomarker for
      RCC. (c) 2015 Wiley Periodicals, Inc.

PMID- 26294354
TI  - Comparison of transcatheter aortic valve and surgical bioprosthetic valve
      durability: A fatigue simulation study.
AB  - Transcatheter aortic valve (TAV) intervention is now the standard-of-care
      treatment for inoperable patients and a viable alternative treatment option for
      high-risk patients with symptomatic aortic stenosis. While the procedure is
      associated with lower operative risk and shorter recovery times than traditional
      surgical aortic valve (SAV) replacement, TAV intervention is still not considered
      for lower-risk patients due in part to concerns about device durability. It is
      well known that bioprosthetic SAVs have limited durability, and TAVs are
      generally assumed to have even worse durability, yet there is little long-term
      data to confirm this suspicion. In this study, TAV and SAV leaflet fatigue due to
      cyclic loading was investigated through finite element analysis by implementing a
      computational soft tissue fatigue damage model to describe the behavior of the
      pericardial leaflets. Under identical loading conditions and with identical
      leaflet tissue properties, the TAV leaflets sustained higher stresses, strains,
      and fatigue damage compared to the SAV leaflets. The simulation results suggest
      that the durability of TAVs may be significantly reduced compared to SAVs to
      about 7.8 years. The developed computational framework may be useful in
      optimizing TAV design parameters to improve leaflet durability, and assessing the
      effects of underexpanded, elliptical, or non-uniformly expanded stent deployment
      on TAV durability. 

PMID- 26294355
TI  - The effects of age and gender on the lumbopelvic rhythm in the sagittal plane in
      309 subjects.
AB  - Frequent upper body bending is associated with low back pain (LBP). The complex
      flexion movement, combining lumbar and pelvic motion, is known as "lumbopelvic
      rhythm" and can be quantified by dividing the change in the lumbar spine
      curvature by the change in pelvic orientation during flexion movement (L/P
      ratio). This parameter is clinically essential for LBP prevention, for diagnostic
      procedures and therapy; however, the effects of age and gender, in detail, are
      unknown. The Epionics SPINE system, utilizing strain-gauge technology and
      acceleration sensors, was used to assess lumbar lordosis and sacrum orientation
      during standing and lumbar angle and sacrum orientation during maximal upper body
      flexion in 309 asymptomatic subjects (age: 20-75 yrs; ?: 134; ?: 175). The
      effects of age and gender on these characteristics as well as on the resultant
      range of flexion (RoF) and lumbopelvic rhythm were investigated. Aging
      significantly reduced lumbar lordosis by 8.2 degrees  and sacrum orientation by
      6.6 degrees  during standing in all subjects. With aging, the lumbar RoF
      decreased by 7.7 degrees , whereas the pelvic RoF compensated for this effect and
      increased by 7.0 degrees . The L/P ratio decreased from 0.80 to 0.65 with age;
      however, this decrease was only significant in men. Gender affected sacrum
      orientation in standing and in flexion as well as the L/P ratio. This study
      demonstrated the effects of age and gender on lordosis, sacrum orientation and
      lumbopelvic rhythm. These findings are of importance for the individual
      prevention of LBP, and provide a baseline for differentiating symptomatic from
      asymptomatic age- and gender-matched subjects.

PMID- 26294356
TI  - Comparison of friction and wear of articular cartilage on different length
      scales.
AB  - The exceptional tribological properties of articular cartilage are still far from
      being fully understood. Articular cartilage is able to withstand high loads and
      provide exceptionally low friction. Although the regeneration abilities of the
      tissue are very limited, it can last for many decades. These biomechanical
      properties are realized by an interplay of different lubrication and wear
      protection mechanisms. The deterioration of cartilage due to aging or injury
      leads to the development of osteoarthritis. A current treatment strategy focuses
      on supplementing the intra-articular fluid with a saline solution containing
      hyaluronic acid. In the work presented here, we investigated how changing the
      lubricating fluid affects friction and wear of articular cartilage, focusing on
      the boundary and mixed lubrication as well as interstitial fluid pressurization
      mechanisms. Different length and time scales were probed by atomic force
      microscopy, tribology and profilometry. We compared aqueous solutions with
      different NaCl concentrations to a viscosupplement containing hyaluronic acid
      (HA). In particular, we found that the presence of ions changes the frictional
      behavior and the wear resistance. In contrast, hyaluronic acid showed no
      significant impact on the friction coefficient, but considerably reduced wear.
      This study confirms the previous notion that friction and wear are not
      necessarily correlated in articular cartilage tribology and that the main role of
      HA might be to provide wear protection for the articular surface. 

PMID- 26294358
TI  - Pressurized Martian-Like Pure CO2 Atmosphere Supports Strong Growth of
      Cyanobacteria, and Causes Significant Changes in their Metabolism.
AB  - Surviving of crews during future missions to Mars will depend on reliable and
      adequate supplies of essential life support materials, i.e. oxygen, food, clean
      water, and fuel. The most economical and sustainable (and in long term, the only
      viable) way to provide these supplies on Martian bases is via bio-regenerative
      systems, by using local resources to drive oxygenic photosynthesis. Selected
      cyanobacteria, grown in adequately protective containment could serve as pioneer
      species to produce life sustaining substrates for higher organisms. The very high
      (95.3 %) CO2 content in Martian atmosphere would provide an abundant carbon
      source for photo-assimilation, but nitrogen would be a strongly limiting
      substrate for bio-assimilation in this environment, and would need to be
      supplemented by nitrogen fertilizing. The very high supply of carbon, with rate
      limiting supply of nitrogen strongly affects the growth and the metabolic
      pathways of the photosynthetic organisms. Here we show that modified, Martian
      like atmospheric composition (nearly 100 % CO2) under various low pressure
      conditions (starting from 50 mbar to maintain liquid water, up to 200 mbars)
      supports strong cellular growth. Under high CO2 / low N2 ratio the filamentous
      cyanobacteria produce significant amount of H2 during light due to
      differentiation of high amount of heterocysts.

PMID- 26294353
TI  - MUC1 (CD227): a multi-tasked molecule.
AB  - Mucin 1 (MUC1 [CD227]) is a high-molecular weight (>400 kDa), type I membrane
      tethered glycoprotein that is expressed on epithelial cells and extends far above
      the glycocalyx. MUC1 is overexpressed and aberrantly glycosylated in
      adenocarcinomas and in hematological malignancies. As a result, MUC1 has been a
      target for tumor immunotherapeutic studies in mice and in humans. MUC1 has been
      shown to have anti-adhesive and immunosuppressive properties, protects against
      infections, and is involved in the oncogenic process as well as in cell
      signaling. In addition, MUC1 plays a key role in the reproductive tract, in the
      immune system (affecting dendritic cells, monocytes, T cells, and B cells), and
      in chronic inflammatory diseases. Evidence for all of these roles for MUC1 is
      discussed herein and demonstrates that MUC1 is truly a multitasked molecule.

PMID- 26294359
TI  - Tolosa-Hunt syndrome: an arcane pathology of cavernous venous sinus.
AB  - Tolosa-Hunt syndrome, an idiopathic granulomatous inflammation of the cavernous
      sinus, is primarily a diagnosis of exclusion. The majority of patients present
      with unilateral orbital pain and features suggestive of paralysis of one or more
      of the cranial nerves passing through the cavernous sinus and/or superior orbital
      fissure. MRI of the head may show unilateral enhancement of the cavernous sinus
      and orbital apex. Treatment is with high-dose intravenous steroids followed by
      tapering oral steroids. Rapid amelioration of pain within 24-48 h supports this
      rare diagnosis. Resolution of neuropathies may take longer. We describe a case of
      a young man who presented with left periorbital pain, complete ophthalmoplaegia
      and ptosis of the left eye. MRI showed enhancement of the left cavernous sinus
      and orbital apex. High dose steroids led to complete resolution of pain, while
      ptosis and ophthalmoplaegia improved gradually. 

PMID- 26294360
TI  - Spinal epidural abscess and meningitis following short-term epidural
      catheterisation for postoperative analgaesia.
AB  - We present a case of a patient with a spinal epidural abscess (SEA) and
      meningitis following short-term epidural catheterisation for postoperative pain
      relief after a laparoscopic sigmoid resection. On the fifth postoperative day, 2
      days after removal of the epidural catheter, the patient developed high fever,
      leucocytosis and elevated C reactive protein. Blood cultures showed a methicillin
      sensitive Staphylococcus aureus infection. A photon emission tomography scan
      revealed increased activity of the spinal canal, suggesting S. aureus meningitis.
      A gadolinium-enhanced MRI showed a SEA that was localised at the epidural
      catheter insertion site. Conservative management with intravenous flucloxacillin
      was initiated, as no neurological deficits were seen. At last follow-up, 8 weeks
      postoperatively, the patient showed complete recovery. 

PMID- 26294361
TI  - Partial malrotation of the bowel in an adult patient presenting with abdominal
      pain.

PMID- 26294362
TI  - Hydatid disease of bone: a dangerous crippling disease.

PMID- 26294363
TI  - Hepatic abscess as a paradoxical response to antituberculous chemotherapy for
      tubercular lymphadenitis.
AB  - Tubercular liver abscess developing as a paradoxical reaction (PR) to
      antitubercular therapy (ATT) is relatively uncommon in the absence of
      disseminated disease and immunocompromised status of the host even in countries
      such as India where the disease is rampant. We report a rare case of hepatic
      abscess that developed paradoxically during antituberculous therapy for
      tubercular lymphadenitis in a 30-year-old woman who tested negative for HIV.
      Diagnosis was performed with the help of ultrasonography (USG)-guided aspiration
      of the abscess followed by cytopathological examination and PCR confirmation of
      the disease from the USG-guided aspirate. The patient responded well to oral
      corticosteroid therapy without any alteration of the ongoing ATT regimen. Details
      of the case and other relevant literature regarding the pathogenesis of this
      event are discussed in detail. 

PMID- 26294365
TI  - Income gradients within child and adolescent antisocial behaviours.
AB  - BACKGROUND: Low income is a widely studied risk factor for child and adolescent
      behavioural difficulties. Previous research on this relationship has produced
      mixed findings. AIMS: To investigate the level, shape and homogeneity of income
      gradients in different types of antisocial behaviour. METHOD: A representative
      sample of 7977 British children and adolescents, aged 5-16 years, was analysed.
      Hypotheses concerning the shapes and homogeneity of the relationships between
      family socioeconomic status and multiple antisocial behaviour outcomes, including
      clinical diagnoses of oppositional-defiant disorder, conduct disorder and symptom
      subscales, such as irritability and hurtfulness, were tested by structural
      equation models. RESULTS: Consistent income gradients were demonstrated across
      all antisocial behaviours studied. Disorder prevalence and mean symptom counts
      decreased across income quintiles in a non-linear fashion. CONCLUSIONS: Our
      findings emphasise that income gradients are similar across different forms of
      antisocial behaviour and indicate that income may lead to greater behavioural
      differences in the mid-income range and less variation at low- and high-income
      extremes.

PMID- 26294364
TI  - The effect of experimentally induced sedentariness on mood and psychobiological
      responses to mental stress.
AB  - BACKGROUND: Evidence suggests a link between sedentary behaviours and depressive
      symptoms. Mechanisms underlying this relationship are not understood, but
      inflammatory processes may be involved. Autonomic and inflammatory responses to
      stress may be heightened in sedentary individuals contributing to risk, but no
      study has experimentally investigated this. AIMS: To examine the effect of
      sedentary time on mood and stress responses using an experimental design. METHOD:
      Forty-three individuals were assigned to a free-living sedentary condition and to
      a control condition (usual activity) in a cross-over, randomised fashion and were
      tested in a psychophysiology laboratory after spending 2 weeks in each condition.
      Participants completed mood questionnaires (General Health Questionnaire and
      Profile of Mood States) and wore a motion sensor for 4 weeks. RESULTS: Sedentary
      time increased by an average of 32 min/day (P = 0.01) during the experimental
      condition compared with control. Being sedentary resulted in increases in
      negative mood independent of changes in moderate to vigorous physical activity
      (DeltaGHQ = 6.23, DeltaPOMS = 2.80). Mood disturbances were associated with
      greater stress-induced inflammatory interleukin-6 (IL-6) responses (beta = 0.37).
      CONCLUSIONS: Two weeks of exposure to greater free-living sedentary time resulted
      in mood disturbances independent of reduction in physical activity. Stress
      induced IL-6 responses were associated with changes in mood.

PMID- 26294366
TI  - Six-year longitudinal course and outcomes of subtypes of depression.
AB  - BACKGROUND: Clinical and aetiological heterogeneity have impeded our
      understanding of depression. AIMS: To evaluate differences in psychiatric and
      somatic course between people with depression subtypes that differed clinically
      (severity) and aetiologically (melancholic v. atypical). METHOD: Data from
      baseline, 2-, 4- and 6-year follow-up of The Netherlands Study of Depression and
      Anxiety were used, and included 600 controls and 648 people with major depressive
      disorder (subtypes: severe melancholic n = 308; severe atypical n = 167; moderate
      n = 173, established using latent class analysis). RESULTS: Those with the
      moderate subtype had a significantly better psychiatric clinical course than the
      severe melancholic and atypical subtype groups. Suicidal thoughts and anxiety
      persisted longer in those with the melancholic subtype. The atypical subtype
      group continued to have the highest body mass index and highest prevalence of
      metabolic syndrome during follow-up, although differences between groups became
      less pronounced over time. CONCLUSIONS: Course trajectories of depressive
      subtypes mostly ran parallel to each other, with baseline severity being the most
      important differentiator in course between groups.

PMID- 26294367
TI  - Empathy in individuals clinically at risk for psychosis: brain and behaviour.
AB  - BACKGROUND: Empathy is a basic human ability, and patients with schizophrenia
      show dysfunctional empathic abilities on the behavioural and neural level. AIMS:
      These dysfunctions may precede the onset of illness; thus, it seems mandatory to
      examine the empathic abilities in individuals at clinical high risk for
      psychosis. METHOD: Using functional magnetic resonance imaging, we measured 15
      individuals at clinical high risk of psychosis (CHR group) and compared their
      empathy performance with 15 healthy volunteers and 15 patients with
      schizophrenia. RESULTS: Behavioural data analysis indicated no significant
      deficit in the CHR group. Functional data analysis revealed hyperactivation in a
      frontotemporoparietal network including the amygdala in the CHR group compared
      with the other two groups. CONCLUSIONS: Despite normal behavioural performance,
      the CHR group activated the neural empathy network differently and specifically
      showed hyperactivation in regions critical for emotion processing. This could
      suggest a compensatory mechanism reflecting emotional hypersensitivity or
      dysfunctional emotion regulation. Further investigations should clarify the role
      of these neural alterations for development and exacerbation of psychosis.

PMID- 26294369
TI  - Complications and mortality in patients with schizophrenia and diabetes:
      population-based cohort study.
AB  - BACKGROUND: The long-term outcome of patients with both diabetes and
      schizophrenia remains unclear. AIMS: To explore whether having schizophrenia
      increases the risk of advanced complications and mortality in people with
      diabetes. METHOD: This is a population-based matched cohort study using Taiwan's
      National Health Insurance Research Database. A total of 11 247 participants with
      diabetes and schizophrenia and 11 247 participants with diabetes but not
      schizophrenia were enrolled. We used Cox proportional hazard models to determine
      the effect of schizophrenia on macrovascular and microvascular complications, and
      all-cause mortality. RESULTS: The adjusted hazard ratios were 1.49 (95% CI 1.32
      1.68) for macrovascular complications, 1.05 (95% CI 0.91-1.21) for microvascular
      complications and 3.68 (95% CI 3.21-4.22) for all-cause mortality in patients
      with diabetes and schizophrenia compared with those patients with diabetes but
      not schizophrenia. CONCLUSIONS: Patients with both diabetes and schizophrenia had
      an increased risk of macrovascular complications and all-cause mortality but did
      not have statistically significant elevated risk of microvascular complications.

PMID- 26294368
TI  - Non-replication of the association between 5HTTLPR and response to psychological
      therapy for child anxiety disorders.
AB  - BACKGROUND: We previously reported an association between 5HTTLPR genotype and
      outcome following cognitive-behavioural therapy (CBT) in child anxiety (Cohort
      1). Children homozygous for the low-expression short-allele showed more positive
      outcomes. Other similar studies have produced mixed results, with most reporting
      no association between genotype and CBT outcome. AIMS: To replicate the
      association between 5HTTLPR and CBT outcome in child anxiety from the Genes for
      Treatment study (GxT Cohort 2, n = 829). METHOD: Logistic and linear mixed
      effects models were used to examine the relationship between 5HTTLPR and CBT
      outcomes. Mega-analyses using both cohorts were performed. RESULTS: There was no
      significant effect of 5HTTLPR on CBT outcomes in Cohort 2. Mega-analyses
      identified a significant association between 5HTTLPR and remission from all
      anxiety disorders at follow-up (odds ratio 0.45, P = 0.014), but not primary
      anxiety disorder outcomes. CONCLUSIONS: The association between 5HTTLPR genotype
      and CBT outcome did not replicate. Short-allele homozygotes showed more positive
      treatment outcomes, but with small, non-significant effects. Future studies would
      benefit from utilising whole genome approaches and large, homogenous samples.

PMID- 26294370
TI  - Criminal justice pathways to psychiatric care for psychosis.
AB  - BACKGROUND: Some patients are at higher risk of contact with criminal justice
      agencies when experiencing a first episode of psychosis. AIMS: To investigate
      whether violence explains criminal justice pathways (CJPs) for psychosis in
      general, and ethnic vulnerability to CJPs. METHOD: Two-year population-based
      survey of people presenting with a first-episode of psychosis. A total of 481
      patients provided information on pathways to psychiatric care. The main outcome
      was a CJP at first contact compared with other services on the care pathway.
      RESULTS: CJPs were more common if there was violence at first presentation (odds
      ratio (OR) = 4.23, 95% CI 2.74-6.54, P<0.001), drug use in the previous year (OR
      = 2.28, 95% CI 1.50-3.48, P<0.001) and for high psychopathy scores (OR = 2.54,
      95% CI 1.43-4.53, P = 0.002). Compared with White British, CJPs were more common
      among Black Caribbean (OR = 2.97, 95% CI 1.54-5.72, P<0.001) and Black African
      patients (OR = 1.95, 95% CI 1.02-3.72, P = 0.01). Violence mediated 30.2% of the
      association for Black Caribbeans, but was not a mediator for Black African
      patients. These findings were sustained after adjustment for age, marital status,
      gender and employment. CONCLUSIONS: CJPs were more common in violent
      presentations, for greater psychopathy levels and drug use. Violence
      presentations did not fully explain ethnic vulnerability to CJPs.

PMID- 26294374
TI  - Dynamic moduli of magneto-sensitive elastomers: a coarse-grained network model.
AB  - The viscoelastic properties of magneto-sensitive elastomers (MSEs) in a low
      frequency regime are studied using a coarse-grained network model. The proposed
      model takes into account the mechanical coupling between magnetic particles
      included in a whole network structure and magnetic interactions between them. We
      show that the application of a constant uniform magnetic field leads to the
      splitting of the relaxation spectrum into two branches for the motions of the
      particles parallel and perpendicular to the field. The shear dynamic moduli G'
      and G'' of MSEs are calculated as a function of frequency. The values of G' and
      G'' are shown to depend on the direction of the shear deformation with respect to
      the magnetic field. For instance, both G' and G'' decrease if the magnetic field
      is applied parallel to the shear velocity (D-geometry) and increase if it is
      applied along the shear gradient (G-geometry). The latter prediction is in a
      qualitative agreement with existing experimental data. The theory allows us to
      analyse experimental data and to extract the structural characteristics of MSEs. 

PMID- 26294371
TI  - Investigating trajectories of social recovery in individuals with first-episode
      psychosis: a latent class growth analysis.
AB  - BACKGROUND: Social disability is a hallmark of severe mental illness yet
      individual differences and factors predicting outcome are largely unknown. AIM:
      To explore trajectories and predictors of social recovery following a first
      episode of psychosis (FEP). METHOD: A sample of 764 individuals with FEP were
      assessed on entry into early intervention in psychosis (EIP) services and
      followed up over 12 months. Social recovery profiles were examined using latent
      class growth analysis. RESULTS: Three types of social recovery profile were
      identified: Low Stable (66%), Moderate-Increasing (27%), and High-Decreasing
      (7%). Poor social recovery was predicted by male gender, ethnic minority status,
      younger age at onset of psychosis, increased negative symptoms, and poor
      premorbid adjustment. CONCLUSIONS: Social disability is prevalent in FEP,
      although distinct recovery profiles are evident. Where social disability is
      present on entry into EIP services it can remain stable, highlighting a need for
      targeted intervention.

PMID- 26294373
TI  - Alteration of the RANKL/RANK/OPG System in Periprosthetic Osteolysis with Septic
      Loosening.
AB  - The pathogenesis of periprosthetic osteolysis with septic loosening remains
      incompletely understood. The purpose of this study was to investigate whether
      expression of the RANKL/RANK/OPG system is altered in septic interface membranes
      (SIMs). Seventeen cases with a SIM, 26 cases with an aseptic interface membrane
      (AIM), and 12 cases with a normal synovium (NS) were assessed. Scanning and
      transmission electron microscopy (SEM and TEM, respectively) were used to observe
      the microscopic morphology of three tissue conditions. Differences in RANKL,
      RANK, and OPG expression at the mRNA level were assessed by real-time
      quantitative PCR, and differences at the protein level were assessed by
      immunohistochemical staining and Western blotting. SEM showed wear debris widely
      distributed on the AIM surface, and TEM showed Bacillus activity in the SIM.
      RANKL expression and the RANKL/OPG ratio were significantly increased in SIMs.
      Imbalance in the RANKL/RANK/OPG system is related to periprosthetic osteolysis
      with septic loosening but is not the only possible pathogenic mechanism. 

PMID- 26294375
TI  - Recent progress in the use of zebrafish for novel cardiac drug discovery.
AB  - INTRODUCTION: Cardiovascular disease is the leading cause of morbidity and
      mortality worldwide, thereby putting a large burden on our healthcare costs.
      Using both human genetic approaches, as well as forward and reverse genetic
      strategies in animal models, significant progress has been made to unravel the
      genetic and molecular etiology of human cardiovascular disease that is crucial to
      define novel therapeutic targets. In this context, the zebrafish has emerged as
      an important in vivo vertebrate animal system to study and to model human
      cardiovascular diseases as well as for in vivo cardiovascular drug discovery.
      AREAS COVERED: This review describes the rationale for using the in vivo model
      system zebrafish in whole-organism-based drug discovery strategies. It also
      highlights recent developments in the fields of drug target identification,
      disease modeling, and automation of high-throughput small compound screening.
      EXPERT OPINION: Novel genome-editing techniques such as the clustered regularly
      interspaced short palindromic repeat/Cas9 (CRISPR/Cas9) and transcription
      activator-like effector nuclease (TALEN) technologies allow highly efficient and
      reliable disease modeling in the in vivo system zebrafish. The ambition of
      developing personalized therapeutic options will clearly be fostered by the
      establishment of animal disease models that accurately simulate the patient's
      situation and the use of these disease models in 'next-generation' high
      throughput small compound screens to define treatment options tailored to
      individual needs. To define suitable targets for therapeutic modulation, systems
      biology approaches that study complex biological systems as an integrated whole
      will pave the way to successful in vivo disease modeling and future drug
      discovery.

PMID- 26294376
TI  - Cyclopropane fatty acid synthase from Oenococcus oeni: expression in Lactococcus
      lactis subsp. cremoris and biochemical characterization.
AB  - Bacterial cyclopropane fatty acid synthases (CFA synthases) catalyze the transfer
      of a methyl group from S-adenosyl-L-methionine (AdoMet) to the double bond of a
      lipid chain, thereby forming a cyclopropane ring. CFAs contribute to resistance
      to acidity, dryness, and osmotic imbalance in many bacteria. This work describes
      the first biochemical characterization of a lactic acid bacterium CFA synthase.
      We have overexpressed Oenococcus oeni CFA synthase in E. coli in order to purify
      the enzyme. The optimum cyclopropanation activity was obtained at pH 5.6 and 35.8
      degrees C. The high K(m) (AdoMet) value obtained (2.26 mM) demonstrates the low
      affinity of O. oeni enzyme toward the L. lactis subsp. cremoris unsaturated
      phospholipids. These results explain the partial complementation of the L. lactis
      subsp. cremoris cfa mutant by the O. oeni cfa gene and suggest a probable
      substrate specificity of the O. oeni enzyme. The current study reveals an
      essential hypothesis about the specificity of O. oeni CFA synthase which could
      play a key function in the acid tolerance mechanisms of this enological
      bacterium.

PMID- 26294377
TI  - Backbone resonance assignments of the human p73 DNA binding domain.
AB  - p53, p63, p73 family of proteins are transcription factors with crucial roles in
      regulating cellular processes such apoptosis, proliferation, differentiation, and
      DNA damage response. The three family members have both overlapping and unique
      biological functions. Sequence and structural homology are greatest in the DNA
      binding domains (DBD), which is the site of the majority of p53 mutations.
      Structurally unstable p53 DBD mutants can associate with themselves or p63 and
      p73 DBDs, impeding tumor suppressor functions. Evidence suggests that these
      proteins associate to form amyloid-like oligomers and fibrils through an
      aggregation-prone sequence within the DBDs. Despite having high sequence and
      structure similarities, p63 and p73 DBDs appear to have considerably lower
      tendencies to be incorporated into p53 aggregates, relative to p53. The backbone
      resonance assignments of p73 DBD reported here complement those previously
      reported for p53 and p63, allowing comparisons and providing molecular insights
      into their biological functions and roles in aggregation and tumor development. 

PMID- 26294379
TI  - Introduction to this Issue: Children's Eyewitness Memory and Testimony in
      Context.

PMID- 26294378
TI  - Long lifespans have evolved with long and monounsaturated fatty acids in birds.
AB  - The evolution of lifespan is a central question in evolutionary biology, begging
      the question why there is so large variation among taxa. Specifically, a central
      quest is to unravel proximate causes of ageing. Here, we show that the degree of
      unsaturation of liver fatty acids predicts maximum lifespan in 107 bird species.
      In these birds, the degree of fatty acid unsaturation is positively related to
      maximum lifespan across species. This is due to a positive effect of
      monounsaturated fatty acid content, while polyunsaturated fatty acid content
      negatively correlates with maximum lifespan. Furthermore, fatty acid chain length
      unsuspectedly increases with maximum lifespan independently of degree of
      unsaturation. These findings tune theories on the proximate causes of ageing
      while providing evidence that the evolution of lifespan in birds occurs in
      association with fatty acid profiles. This suggests that studies of proximate and
      ultimate questions may facilitate our understanding of these central evolutionary
      questions. 

PMID- 26294380
TI  - Gating Out Misinformation: Can Young Children Follow Instructions to Ignore False
      Information?
AB  - The current study investigated the effects of misinformation on children's memory
      reports after practice with the logic-of-opposition instruction at time of test.
      Four- and 6-year-old children participated in a play event in Session 1. During a
      two-week delay, parents presented their children with either misinformation or
      correct information about the play event. Prior to a memory interview in Session
      2, some misled children were given a developmentally appropriate logic-of
      opposition instruction to not report information provided by their parents.
      Results indicated that children were misled by the incorrect information, but
      that the logic-of-opposition instruction aided in the children's retrieval of the
      original memory, particularly for the 6-year-olds. Implications of the results
      for memory malleability and social demand effects in children are discussed.

PMID- 26294381
TI  - Simulating Memory Impairment for Child Sexual Abuse.
AB  - The current study investigated effects of simulated memory impairment on recall
      of child sexual abuse (CSA) information. A total of 144 adults were tested for
      memory of a written CSA scenario in which they role-played as the victim. There
      were four experimental groups and two testing sessions. During Session 1,
      participants read a CSA story and recalled it truthfully (Genuine group), omitted
      CSA information (Omission group), exaggerated CSA information (Commission group),
      or did not recall the story at all (No Rehearsal group). One week later, at
      Session 2, all participants were told to recount the scenario truthfully, and
      their memory was then tested using free recall and cued recall questions. The
      Session 1 manipulation affected memory accuracy during Session 2. Specifically,
      compared with the Genuine group's performance, the Omission, Commission, or No
      Rehearsal groups' performance was characterized by increased omission and
      commission errors and decreased reporting of correct details. Victim blame
      ratings (i.e., victim responsibility and provocativeness) and participant gender
      predicted increased error and decreased accuracy, whereas perpetrator blame
      ratings predicted decreased error and increased accuracy. Findings are discussed
      in relation to factors that may affect memory for CSA information.

PMID- 26294382
TI  - The Effects of Practice on Children's Ability to Apply Ground Rules in a
      Narrative Interview.
AB  - Despite the widespread use of ground rules in forensic interview guidelines, it
      is unknown whether children retain and apply these rules throughout narrative
      interviews. We evaluated the capacity of 260 five- to nine-year-olds to utilize
      three ground rules. At the beginning of the interview all children heard the
      rules; half also practiced them. Children then responded to open-ended prompts
      about a repeated laboratory event and were assessed for their application of the
      rules. Logistic regressions revealed that practice only benefitted the use of the
      "don't know" rule. Although the children accurately answered "don't understand"
      and "correct me" practice questions, practice appeared to give no greater benefit
      than just hearing the rules. Results suggest that the current format of ground
      rule practice in interview guidelines is appropriate for the "don't know" rule,
      but the other rules may require more extensive practice with this age group.

PMID- 26294383
TI  - Preparing Children for Court: Effects of a Model Court Education Program on
      Children's Anticipatory Anxiety.
AB  - The current study examined whether a pretrial preparation program, consisting of
      legal knowledge education, stress inoculation training, and a mock trial, is
      associated with decreased anticipatory anxiety of child witnesses. One hundred
      and ninety-three 4- to 17-year-olds who were awaiting impending legal proceedings
      attended Kids' Court School in Las Vegas, NV, one to two weeks before their court
      appearances. Participants completed a measure of anticipatory court-related
      anxiety before and after the intervention. As predicted, children's anticipatory
      anxiety decreased significantly from pretest to posttest. Results demonstrate the
      promise of a brief, unbiased, standardized program for reducing system-induced
      stress on child witnesses, while maintaining the integrity of the legal process.
      This study serves as a springboard to guide future research, practice, policy,
      and implementation on a larger scale.

PMID- 26294384
TI  - Improving the Credibility of Child Sexual Assault Victims in Court: The Impact of
      a Sexual Assault Nurse Examiner.
AB  - The present study investigated the influence of a sexual assault nurse examiner's
      (SANE's) testimony on mock juror perceptions of a child or adolescent victim of
      child sexual assault. Community members (N = 252, 156 females) read a fictional
      criminal trial summary of a child sexual assault case in which the victim was 6
      or 15 years old and the prosecution presented medical testimony from a SANE or a
      traditional registered nurse (RN), or did not present medical testimony. Mock
      jurors were more likely to render guilty verdicts when a SANE testified compared
      with the other two testimony conditions. In addition, pro-victim judgments (e.g.,
      sympathy toward the victim) and negative defendant judgments (e.g., anger toward
      the defendant) mediated this relation. Finally, cognitive network representations
      of the case demonstrated that the RN and no-medical-testimony groups were similar
      and the SANE group was distinct from the other two conditions. We discuss these
      results in terms of the implications of SANE testimony in child sexual assault
      court cases.

PMID- 26294385
TI  - Support Person Presence and Child Victim Testimony: Believe it or Not.
AB  - This study examined the effects of support person presence on participants'
      perceptions of an alleged child sexual abuse victim and defendant. Two hundred
      jury-eligible community members (n = 100 males) viewed a DVD of an 11-year-old
      girl's simulated courtroom testimony either with or without a female support
      person seated next to her. Participants found the child victim to be less
      accurate and trustworthy, and the defendant to be less guilty and less likely to
      have sexually abused children, when the support person was present. Participants
      who viewed the female support person (n = 100) believed that she had probably
      coached and spent a great deal of time with the child victim before testifying.
      Female participants perceived the child to be more accurate, and the defendant to
      be more guilty and likely to have sexually abused children, than male
      participants. The degree to which the child victim's testimonial behavior
      violated participants' expectancies mediated the negative relation between
      support person presence and child victim accuracy and trustworthiness. Support
      person presence was positively associated with expectancy violation, which in
      turn was negatively associated with child victim accuracy and trustworthiness.
      These preliminary findings suggest that seating a support person next to an
      alleged child victim in court may have the unintended effect of decreasing the
      child's perceived credibility and, if replicated, suggest that alternative
      seating arrangements might be necessary.

PMID- 26294386
TI  - Religion-Related Child Maltreatment: A Profile of Cases Encountered by Legal and
      Social Service Agencies.
AB  - Religion can foster, facilitate, and be used to justify child maltreatment. Yet
      religion-related child abuse and neglect have received little attention from
      social scientists. We examined 249 cases of religion-related child maltreatment
      reported to social service agencies, police departments, and prosecutors' offices
      nationwide. We focused on cases involving maltreatment perpetrated by persons
      with religious authority, such as ministers and priests; the withholding of
      medical care for religious reasons; and abusive attempts to rid a child of
      supposed evil. By providing a descriptive statistical profile of the major
      features of these cases, we illustrate how these varieties of religion-related
      child maltreatment occur, who the victims and perpetrators are, and how religion
      related child abuse and neglect are reported and processed by the social service
      and criminal justice systems. We end with a call for greater research attention
      to these important offenses against children.

PMID- 26294387
TI  - Blessed be the Children: A Case-Control Study of Sexual Abusers in the Catholic
      Church.
AB  - Individuals working in churches and other youth-serving institutions have a
      unique level of access to children, yet the problem of sexual abuse in
      institutional settings has received scant research attention. To address this
      gap, we analyzed data from a large sample of clergy (N = 1,121) and applied a
      social-ecological model of offending to identify risk factors for sexual abuse
      perpetration. Using a case-control study design that compared clergy sexual
      abusers with three control groups of clergy, this study focuses specifically on
      individual-, relationship-, and community-level factors associated with a higher
      risk of abuse in professional populations. Findings revealed that clergy sexual
      abusers tended to have more truncated pre-seminary dating histories, and that
      their dating and sexual partners were more likely to have been male than female.
      Self-reported sexual abuse history was associated with a greater likelihood of
      sexual abuse perpetration among clergy. Clergy abusers tended to be more involved
      with youth and adolescents in their ministries; however, they were observed to
      relate less well to youth and adolescents than their clergy counterparts. Given
      widespread changes in our cultural understanding of abuse as well as more
      specific changes in the organizational approach to seminary education, these
      differences underscore the role that youth-serving institutions and society can
      have in the primary prevention of child sexual abuse.

PMID- 26294389
TI  - The third principal direction besides armchair and zigzag in single-layer black
      phosphorus.
AB  - Armchair and zigzag are two popular principal directions in many quasi-two
      dimensional nanostructures such as graphene, hexagonal boron nitride, and black
      phosphorus. To date, nearly all published works discuss the anisotropy for
      physical quantities based on the comparison between quantity values in these two
      principal directions in single-layer black phosphorus. However, in the present
      work, by analyzing the directional dependence for the Young's modulus with an
      analytic formula, we explore the third principal direction with a direction angle
      phi(tp) = 0.268pi, besides the armchair and zigzag directions. This new principal
      direction is determined by the puckered configuration of black phosphorus. The
      largest Young's modulus value is neither in the armchair, nor in the zigzag
      direction. Instead it is the third principle direction along which the Young's
      modulus has the maximum value. This work reveals that armchair and zigzag
      directions are not enough for the discussion of anisotropic properties in the
      single-layer black phosphorus, and it is crucial to include this new principal
      direction for anisotropy discussions.

PMID- 26294388
TI  - Dual effects of fibroblast growth factor 21 on hepatic energy metabolism.
AB  - The aim of this study was to investigate the mechanisms by which fibroblast
      growth factor 21 (FGF21) affects hepatic integration of carbohydrate and fat
      metabolism in Siberian hamsters, a natural model of adiposity. Twelve aged
      matched adult male Siberian hamsters maintained in their long-day fat state since
      birth were randomly assigned to one of two treatment groups and were continuously
      infused with either vehicle (saline; n=6) or recombinant human FGF21 protein (1
      mg/kg per day; n=6) for 14 days. FGF21 administration caused a 40% suppression
      (P<0.05) of hepatic pyruvate dehydrogenase complex (PDC), the rate-limiting step
      in glucose oxidation, a 34% decrease (P<0.05) in hepatic acetylcarnitine
      accumulation, an index of reduced PDC flux, a 35% increase (P<0.05) in long-chain
      acylcarnitine content (an index of flux through beta-oxidation) and a 47%
      reduction (P<0.05) in hepatic lipid content. These effects were underpinned by
      increased protein abundance of PD kinase-4 (PDK4, a negative regulator of PDC),
      the phosphorylated (inhibited) form of acetyl-CoA carboxylase (ACC, a negative
      regulator of delivery of fatty acids into the mitochondria) and the
      transcriptional co-regulators of energy metabolism peroxisome proliferator
      activated receptor gamma co-activator alpha (PGC1alpha) and sirtuin-1. These
      findings provide novel mechanistic basis to support the notion that FGF21 exerts
      profound metabolic benefits in the liver by modulating nutrient flux through both
      carbohydrate (mediated by a PDK4-mediated suppression of PDC activity) and fat
      (mediated by deactivation of ACC) metabolism, and therefore may be an attractive
      target for protection from increased hepatic lipid content and insulin resistance
      that frequently accompany obesity and diabetes. 

PMID- 26294391
TI  - Comparative accuracy of preoperative tumor size assessment on mammography,
      sonography, and MRI: Is the accuracy affected by breast density or cancer
      subtype?
AB  - PURPOSE: To compare the accuracy of preoperative breast tumor size measurements
      obtained on three imaging modalities (mammography [MM], sonography [US], and MRI)
      with those obtained on final pathologic examination for different breast
      densities and various tumor types. METHODS: Records from patients who underwent
      breast cancer lumpectomy between 2008 and 2012 and in whom tumor was seen on all
      three imaging modalities were retrospectively reviewed for maximum tumor size
      measurements. Patients with positive tumor margins and those who had undergone
      neoadjuvant chemotherapy were excluded. Tumor size measurements obtained on the
      three imaging modalities were compared for accuracy with those obtained during
      the final pathologic examination. Differences were analyzed for the whole group
      and for subgroups according to breast density and tumor type. RESULTS: In total,
      57 patients were included, in whom wire-localization lumpectomy was performed
      without neoadjuvant chemotherapy; negative surgical margins for tumor were
      obtained, and tumor was preoperatively visualized on all three imaging
      modalities. The mean (+/- SEM) tumor size measured on MRI was significantly
      greater than that measured on pathology (p < 0.001), whereas the sizes measured
      on US and MM were not statistically significantly different from that measured on
      pathology (p = 0.62 and p = 0.57). Tumor size measured on MRI was greater than
      that measured on both US and MM (p = 0.003 and p < 0.001). Compared with the
      measurements obtained on pathology, that obtained on US showed moderate agreement
      (Lin concordance correlation coefficient [CCC], 0.71; 95% confidence interval
      [CI], 0.56-0.82); poorer agreement was found for the sizes obtained on MM (CCC,
      0.58; 95% CI, 0.38-0.72) and MRI (CCC, 0.50; 95% CI, 0.31-0.65). No difference in
      comparative accuracy of size measurement was noted between dense and nondense
      breast tissue. MRI overestimated tumor size in ductal cancers (p < 0.001) and
      slightly underestimated it in lobular cancers. CONCLUSIONS: Preoperative MRI
      significantly overestimated tumor size. Measurements obtained on US and MM were
      more accurate irrespective of breast density, with US measurements being slightly
      more accurate than MM measurements.

PMID- 26294390
TI  - A thiol-disulfide oxidoreductase of the Gram-positive pathogen Corynebacterium
      diphtheriae is essential for viability, pilus assembly, toxin production and
      virulence.
AB  - The Gram-positive pathogen Corynebacterium diphtheriae exports through the Sec
      apparatus many extracellular proteins that include the key virulence factors
      diphtheria toxin and the adhesive pili. How these proteins attain their native
      conformations after translocation as unfolded precursors remains elusive. The
      fact that the majority of these exported proteins contain multiple cysteine
      residues and that several membrane-bound oxidoreductases are encoded in the
      corynebacterial genome suggests the existence of an oxidative protein-folding
      pathway in this organism. Here we show that the shaft pilin SpaA harbors a
      disulfide bond in vivo and alanine substitution of these cysteines abrogates SpaA
      polymerization and leads to the secretion of degraded SpaA peptides. We then
      identified a thiol-disulfide oxidoreductase (MdbA), whose structure exhibits a
      conserved thioredoxin-like domain with a CPHC active site. Remarkably, deletion
      of mdbA results in a severe temperature-sensitive cell division phenotype. This
      mutant also fails to assemble pilus structures and is greatly defective in toxin
      production. Consistent with these defects, the DeltamdbA mutant is attenuated in
      a guinea pig model of diphtheritic toxemia. Given its diverse cellular functions
      in cell division, pilus assembly and toxin production, we propose that MdbA is a
      component of the general oxidative folding machine in C. diphtheriae. 

PMID- 26294393
TI  - Flexible Transparent Films Based on Nanocomposite Networks of Polyaniline and
      Carbon Nanotubes for High-Performance Gas Sensing.
AB  - A flexible, transparent, chemical gas sensor is assembled from a transparent
      conducting film of carbon nanotube (CNT) networks that are coated with
      hierarchically nanostructured polyaniline (PANI) nanorods. The nanocomposite film
      is synthesized by in-situ, chemical oxidative polymerization of aniline in a
      functional multiwalled CNT (FMWCNT) suspension and is simultaneously deposited
      onto a flexible polyethylene terephthalate (PET) substrate. An as-prepared
      flexible transparent chemical gas sensor exhibits excellent transparency of 85.0%
      at 550 nm using the PANI/FMWCNT nanocomposite film prepared over a reaction time
      of 8 h. The sensor also shows good flexibility, without any obvious decrease in
      performance after 500 bending/extending cycles, demonstrating high-performance,
      portable gas sensing at room temperature. This superior performance could be
      attributed to the improved electron transport and collection due to the CNTs,
      resulting in reliable and efficient sensing, as well as the high surface-to
      volume ratio of the hierarchically nanostructured composites. The excellent
      transparency, improved sensing performance, and superior flexibility of the
      device, may enable the integration of this simple, low-cost, gas sensor into
      handheld flexible transparent electronic circuitry and optoelectronic devices. 

PMID- 26294392
TI  - Divergent modulation of Rho-kinase and Ca(2+) influx pathways by Src family
      kinases and focal adhesion kinase in airway smooth muscle.
AB  - BACKGROUND AND PURPOSE: The importance of tyrosine kinases in airway smooth
      muscle (ASM) contraction is not fully understood. The aim of this study was to
      investigate the role of Src-family kinases (SrcFK) and focal adhesion kinase
      (FAK) in GPCR-mediated ASM contraction and associated signalling events.
      EXPERIMENTAL APPROACH: Contraction was recorded in intact or alpha-toxin
      permeabilized rat bronchioles. Phosphorylation of SrcFK, FAK, myosin light-chain
      20 (MLC20 ) and myosin phosphatase targeting subunit-1 (MYPT-1) was evaluated in
      cultured human ASM cells (hASMC). [Ca(2+) ]i was evaluated in Fura-2 loaded
      hASMC. Responses to carbachol (CCh) and bradykinin (BK) and the contribution of
      SrcFK and FAK to these responses were determined. KEY RESULTS: Contractile
      responses in intact bronchioles were inhibited by antagonists of SrcFK, FAK and
      Rho-kinase, while after alpha-toxin permeabilization, they were sensitive to
      inhibition of SrcFK and Rho-kinase, but not FAK. CCh and BK increased
      phosphorylation of MYPT-1 and MLC20 and auto-phosphorylation of SrcFK and FAK.
      MYPT-1 phosphorylation was sensitive to inhibition of Rho-kinase and SrcFK, but
      not FAK. Contraction induced by SR Ca(2+) depletion and equivalent [Ca(2+) ]i
      responses in hASMC were sensitive to inhibition of both SrcFK and FAK, while
      depolarization-induced contraction was sensitive to FAK inhibition only. SrcFK
      auto-phosphorylation was partially FAK-dependent, while FAK auto-phosphorylation
      was SrcFK-independent. CONCLUSIONS AND IMPLICATIONS: SrcFK mediates Ca(2+) 
      sensitization in ASM, while SrcFK and FAK together and individually influence
      multiple Ca(2+) influx pathways. Tyrosine phosphorylation is therefore a key
      upstream signalling event in ASM contraction and may be a viable target for
      modulating ASM tone in respiratory disease.

PMID- 26294394
TI  - 200 Million Thymocytes and I: A Beginner's Survival Guide to T Cell Development.
AB  - T lymphocytes (T cells) are essential for proper adaptive immune responses. They
      perform a variety of functions in defenses against pathogens, and notably
      control, positively or negatively, other cells involved in immune responses. T
      cells develop in the thymus from bone marrow-derived precursors. These precursors
      (thymocytes) proliferate, rearrange the genes encoding subunits of the T cell
      antigen receptor, which endow them with their unique antigen specificity, and
      undergo various degrees of pre-programming for their functions in immune
      responses. Thus, analyzing T cell development in the thymus is essential for
      understanding their functions in immune responses. In addition, the thymus
      constitutes an attractive experimental model to analyze mechanisms of cell
      proliferation, differentiation and survival, all of which are involved in
      thymocyte development. This chapter presents a quick overview of the key events
      characterizing intrathymic T cell development, as an introduction for readers
      entering this field of study. 

PMID- 26294395
TI  - Development of gammadelta T Cells, the Special-Force Soldiers of the Immune
      System.
AB  - While the functions of alphabeta T cells in host resistance to pathogen infection
      are understood in far more detail than those of gammadelta lineage T cells,
      gammadelta T cells perform critical, essential functions during immune responses
      that cannot be compensated by alphabeta T cells. Accordingly, it is essential to
      understand how the development of gammadelta T cells is controlled so that their
      generation and function might be manipulated in future for therapeutic benefit.
      This introductory chapter will cover the basic processes that underlie gammadelta
      T cell development in the thymus, as well as the current understanding of how
      they are controlled. 

PMID- 26294396
TI  - Genetic Tools to Study T Cell Development.
AB  - Genetics tools, and especially the ability to enforce, by transgenesis, or
      disrupt, by homologous recombination, gene expression in a cell-specific manner,
      have revolutionized the study of immunology and propelled the laboratory mouse as
      the main model to study immune responses. Perhaps more than any other aspect of
      immunology, the study of T cell development has benefited from these
      technologies. This brief chapter summarizes genetic tools specific to T cell
      development studies, focusing on mouse strains with lineage- and stage-specific
      expression of the Cre recombinase, or expressing unique antigen receptor
      specificities. It ends with a broader discussion of strategies to enforce ectopic
      lineage and stage-specific gene expression. 

PMID- 26294397
TI  - Assessment of T Cell Development by Flow Cytometry.
AB  - T cell development is a complex multistep process that requires the coordinated
      activation of distinct signaling responses and the regulated progression of
      developing cells (thymocytes) through key stages of maturation. Although
      sophisticated techniques such as fetal thymus organ culture, in vitro thymocyte
      culture, and multi-parameter flow cytometric analysis are now widely employed to
      evaluate thymocyte maturation by experienced laboratories, defects in T cell
      development can usually be identified with more simplified screening methods.
      Here, we provide a basic protocol for assessment of T cell development that will
      enable laboratories with access to a four parameter flow cytometer to screen
      mouse strains, including those generated from embryonic stem cells with targeted
      gene mutations, for thymocyte maturation defects. 

PMID- 26294398
TI  - Flow Cytometry Analysis of Thymic Epithelial Cells and Their Subpopulations.
AB  - The parenchyma of the thymus is compartmentalized into the cortex and the
      medulla, which are constructed by cortical thymic epithelial cells (cortical
      TECs, cTECs) and medullary thymic epithelial cells (mTECs), respectively. cTECs
      and mTECs essentially and differentially regulate the development and repertoire
      selection of T cells. Consequently, the biology of T cell development and
      selection includes the study of TECs in addition to the study of developing T
      cells and other hematopoietic cells including dendritic cells. In this chapter,
      we describe the methods for flow cytometric analysis and sorting of TECs and
      their subpopulations, including cTECs and mTECs. 

PMID- 26294399
TI  - Identifying the Spatial Relationships of Thymic Stromal and Thymocyte Subsets by
      Immunofluorescence Analysis.
AB  - Immunofluorescence analysis of thymic tissue sections is an indispensable
      technique for visualizing spatial relationships among thymocyte and stromal cell
      subsets. The thymus is organized into distinct microenvironmental zones in which
      particular thymic epithelial cell (TEC) subsets support specific stages of
      thymocyte maturation. Conversely, thymocytes and lymphoid tissue inducer cells
      support functional maturation of TECs. The composition and organization of TECs
      change during ontogeny to generate a maximally functional organ in the young
      adult. Deterioration of thymic architecture and stromal organization occurs with
      age as the thymus undergoes involution. Such changes can be monitored by
      immunofluorescent staining of thymic sections obtained at different ages
      throughout the life-span. Here we describe methods to generate frozen or paraffin
      embedded thymic tissue sections for multicolor immunofluorescence staining using
      antibodies to surface and/or cytoplasmic antigens. 

PMID- 26294400
TI  - Purification of Thymocyte and T Cell Subsets.
AB  - Many analytical or cell culture procedures require homogeneous starting cell
      populations that cannot be obtained directly from organ dissection. Here, we
      describe two enrichment procedures to achieve this goal and discuss their
      respective advantages in specific experimental contexts. Notes in this chapter
      include some tips on how to determine the appropriate level of purity (see Note 1
      ). 

PMID- 26294401
TI  - Retroviral Transduction of T Cells and T Cell Precursors.
AB  - Transduction of lymphoid progenitors with retroviral or lentiviral vectors is a
      powerful experimental strategy to tease out the role of a gene or pathway in T
      cell development via gain-of-function or loss-of-function strategies. Here we
      discuss different approaches to use this powerful technology, and present some
      protocols that we use to transduce murine HSCs, thymocytes, and lymphoid cell
      lines with these viral vectors. 

PMID- 26294402
TI  - Bone Marrow and Fetal Liver Radiation Chimeras.
AB  - Radiation chimeras are prepared by subjecting recipient mice to sublethal or
      lethal dose of irradiation and injecting them with hematopoietic stem cells (HSC)
      from untreated donor mice. HSC can be obtained from bone marrow or fetal liver.
      This technique is a powerful tool when coupled with gene targeting strategies to
      investigate function of HSCs, thymocyte development, and T cell function. This
      protocol describes how to produce bone marrow or fetal liver chimeras. 

PMID- 26294403
TI  - In Vitro Analyses of T Cell Effector Differentiation.
AB  - In vitro culture is an important complement, or substitute, to in vivo approaches
      in order to study T cell effector differentiation. Here, we describe culture
      conditions that generate specific effector cell types by exposing naive T cells
      to appropriate cytokine signals. 

PMID- 26294404
TI  - Studying T Cell Development in Thymic Slices.
AB  - Recently, tissue slices have been adapted to study both mouse and human T cell
      development. Thymic slices combine and complement the strengths of existing
      organotypic culture systems to study thymocyte differentiation. Specifically, the
      thymic slice system allows for high throughput experiments and the ability to
      introduce homogenous developmental intermediate populations into an environment
      with a well-established cortex and medulla. These qualities make thymic slices a
      highly versatile and technically accessible model to study thymocyte development.
      Here we describe methods to prepare, embed, and slice thymic lobes to study T
      cell development in situ. 

PMID- 26294405
TI  - FTOC-Based Analysis of Negative Selection.
AB  - Potentially harmful T cell precursors are removed from the conventional T cell
      pool by negative selection. This process can involve the induction of apoptosis,
      anergy, receptor editing or deviation into a regulatory T cell lineage. As such
      this process is essential for the health of an organism through its contribution
      to central and peripheral tolerance. While a great deal is known about the
      process, the precise mechanisms that regulate negative selection are not clear.
      Furthermore, the signals that distinguish the different forms of negative
      selection are not fully understood. Numerous models exist with the potential to
      address these questions in vitro and in vivo. This chapter describes methods of
      fetal thymic organ culture designed to analyze the signals that determine these
      unique cell fates. 

PMID- 26294406
TI  - Reconstituted Thymus Organ Culture.
AB  - Reconstituted thymus organ culture is based on fetal thymus organ culture (FTOC).
      Purified thymocyte populations, from genetically modified mice or even from other
      species, are cultured in vitro with thymic lobes depleted of their endogenous
      thymocytes (by 2'-deoxyguanosine treatment) to form a new thymus. This potent and
      timesaving method is distinct from FTOC, which assesses development of unmodified
      thymic lobes, and reaggregate thymic organ culture, in which epithelial cells are
      separately purified before being aggregated with thymocytes. 

PMID- 26294407
TI  - Induction of T Cell Development In Vitro by Delta-Like (Dll)-Expressing Stromal
      Cells.
AB  - Recreating the thymic microenvironment in vitro poses a great challenge to
      immunologists. Until recently, the only approach was to utilize the thymic tissue
      in its three-dimensional form and to transfer the hematopoietic progenitors into
      this tissue to generate de novo T cells. With the advent of OP9-DL cells (bone
      marrow-derived cells that are transduced to express Notch ligand, Delta-like),
      hematopoietic stem cells (HSC) could be induced to differentiate into T cells in
      culture for the first time outside of the thymic tissue on a monolayer. We, as
      well as others, asked whether the ability to support T cell development in vitro
      in a monolayer is unique to BM-derived OP9 cells, and showed that provision of
      Delta-like expression to thymic epithelial cells and fibroblasts also allowed for
      T cell development. This provides the opportunity to design an autologous
      coculture system where the supportive stromal and the hematopoietic components
      are both derived from the same individual, which has obvious clinical
      implications. In this chapter, we describe methods for establishing a primary
      murine dermal fibroblast cell population that is transduced to express Delta-like
      4, and describe the conditions for its coculture with HSCs to support T cell
      lineage initiation and expansion, while comparing it to the now classic OP9-DL
      coculture. 

PMID- 26294408
TI  - In Vitro Analysis of Thymocyte Signaling.
AB  - From the moment a developing thymocyte expresses a TCR, it is subjected to
      numerous interactions with self-peptide/MHC complexes that determine its ultimate
      fate. These include death by neglect, negative selection (apoptosis and lineage
      deviation), positive selection, and lineage commitment. The identification of
      signals that govern these unique cell fates requires the ability to assess the
      activity, level of expression, subcellular location, and the molecular
      associations of numerous proteins within the developing T cell. Thus, this
      chapter describes methods designed to analyze thymocyte signaling under various
      types of peptide-based stimulation in vitro. 

PMID- 26294409
TI  - Molecular Analysis of Mouse T Cell Receptor alpha and beta Gene Rearrangements.
AB  - PCR on genomic DNA isolated from lymphocyte populations is an invaluable
      technique to analyze T cell receptor (TCR) alpha and beta gene rearrangements.
      Although this approach is powerful, it also has limitations that must be
      accounted for in experimental design and data interpretation. Here, we provide
      background required for understanding these limitations, and then outline
      standard PCR methods that can be used for analysis of TCRalpha and beta gene
      rearrangements in mice. 

PMID- 26294410
TI  - Intrathymic Injection.
AB  - Intrathymic injection is used in several T cell-associated immunological studies
      to deliver cells or other substances directly into the thymus. Here, we describe
      the intrathymic injection procedure involving surgical incision of the mouse with
      or without a thoracotomy. Though this procedure can result in poor recovery,
      postsurgical complications, and distress to the animal, it is actually a simple
      procedure that can be carried out relatively easily and quickly with experience. 

PMID- 26294411
TI  - Analysis of Cell Proliferation and Homeostasis Using EdU Labeling.
AB  - Determination of cellular proliferation and population turnover is an important
      tool for research on lymphoid cell function. Historically this has been done
      using radiolabeled nucleotides or nucleoside analogs, such as BrdU (5-bromo-2
      deoxyuridine), that are incorporated into nascent DNA during S-phase. Recently, a
      new procedure was developed to label nascent DNA using EdU (5-Ethynyl-2
      deoxyuridine). This new method overcomes limitations imposed by the procedure
      used to detect BrdU because EdU detection is based on an easily performed
      chemical reaction that does not require DNA denaturation, is quick and
      reproducible, and has a superior signal-to-noise ratio. This technique offers a
      wide range of opportunities to analyze cellular proliferation, population
      homeostasis, and cell marking procedures. 

PMID- 26294412
TI  - Characterization and Isolation of Human T Cell Progenitors.
AB  - During their development, human T cells undergo similar genomic changes and pass
      through the same developmental checkpoints as developing thymocytes in the mouse.
      The difference between both species, however, is that some of these developmental
      stages are characterized by different phenotypic markers and as a result,
      evidence emerges that the molecular regulation of human T cell development subtly
      differs from the mouse [1-4]. In this chapter, we describe in detail how the
      different stages of human T cell development can be characterized and isolated
      using specific surface markers. 

PMID- 26294414
TI  - Humanized Mice to Study Human T Cell Development.
AB  - While in vitro models exist to study human T cell development, they still lack
      the precise environmental stimuli, such as the exact combination and levels of
      cytokines and chemokines, that are present in vivo. Moreover, studying the homing
      of hematopoietic stem (HSC) and progenitor (HPC) cells to the thymus can only be
      done using in vivo models. Although species-specific differences exist,
      "humanized" models are generated to circumvent these issues. In this chapter, we
      focus on the humanized mouse models that can be used to study early T cell
      development. Models that study solely mature T cells, such as the SCID-PBL (Tary
      Lehmann et al., Immunol Today 16:529-533) are therefore not discussed here, but
      have recently been reviewed (Shultz et al., Nat Rev Immunol 12:786-798).

PMID- 26294413
TI  - Approaches to Study Human T Cell Development.
AB  - Not only is human T cell development characterized by unique changes in surface
      marker expression, but it also requires specific growth factors and conditions to
      mimic and study T cell development in vitro. In this chapter, we provide an
      overview of the specific aspects that need attention when performing T cell
      differentiation cultures with human progenitors. 

PMID- 26294415
TI  - Using the Zebrafish Model to Study T Cell Development.
AB  - While zebrafish have for some time been regarded as a powerful model organism
      with which to study early events in hematopoiesis, recent evidence suggests that
      it also ideal for unraveling the molecular requirements for T cell development in
      the thymus. Like mammals, zebrafish possess an adaptive immune system, comprising
      B lymphocytes as well as both the gammadelta and alphabeta lineages of T cells,
      which develop in the thymus. Moreover, the molecular processes underlying T cell
      development in zebrafish appear to be remarkably conserved. Thus, findings in the
      zebrafish model will be of high relevance to the equivalent processes in mammals.
      Finally, molecular processes can be interrogated in zebrafish far more rapidly
      than is possible in mammals because the zebrafish possesses many unique
      advantages. These unique attributes, and the methods by which they can be
      exploited to investigate the role of novel genes in T cell development, are
      described here. 

PMID- 26294416
TI  - Mini vs. Standard Implants for Mandibular Overdentures: A Randomized Trial.
AB  - A mandibular implant-retained overdenture is considered a first-choice treatment
      for edentulism. However, some aspects limit the use of standard implants-for
      example, the width of edentulous ridges, chronic diseases, fear, or costs. This
      randomized trial compared mandibular overdentures retained by 2 or 4 mini
      implants with standard implants, considering oral health-related quality of life
      (OHRQoL), patient satisfaction, and complications such as lost implant. In sum,
      120 edentulous men and women (mean age, 59.5 +/- 8.5 y) randomly received 4 mini
      implants, 2 mini-implants, or 2 standard implants. Participants provided data
      regarding OHRQoL and satisfaction until 12 mo. Clinical parameters, including
      implant survival rate, were also recorded. Both 2 and 4 mini-implants led to
      better OHRQoL, compared with 2 standard implants. Treatment with 4 mini-implants
      was more satisfying than 2 standard implants, with 2 mini-implants presenting
      intermediate results. Implant survival rate was 89%, 82%, and 99% for 4 mini
      implants, 2 mini-implants, or 2 standard implants, respectively. Overdentures
      retained by 4 or 2 mini-implants can achieve OHRQoL and satisfaction at least
      comparable with that of 2 standard implants. However, the survival rate of mini
      implants is not as high as that of standard implants (ClinicalTrials.gov
      NCT01411683). 

PMID- 26294417
TI  - An update on the efficacy of endobronchial valve therapy in the management of
      hyperinflation in patients with chronic obstructive pulmonary disease.
AB  - Lung volume reduction surgery has been shown to be effective in patients with
      heterogeneous emphysema, but is also associated with a relatively high
      perioperative morbidity and mortality. Accordingly, several novel and potentially
      less invasive methods for bronchoscopic lung volume reduction have been
      developed. Endobronchial valve (EBV) therapy is one such therapeutic approach in
      patients with advanced emphysema. It has been the most widely studied technique
      over the past years and represents an effective treatment option for patients
      with severe heterogeneous upper- or lower-lobe-predominant emphysema. The choice
      of EBV therapy largely depends on the distribution of emphysema and the presence
      or absence of interlobar collateral ventilation. Adequate patient selection and
      technical success of valve implantation with the intention of lobar exclusion are
      predictive factors for positive outcomes. This review attempts to highlight the
      milestones in the development of bronchoscopic lung volume reduction with one-way
      valve implantation over the past few years. 

PMID- 26294418
TI  - The role of inhaled prostacyclin in treating acute respiratory distress syndrome.
AB  - Acute respiratory distress syndrome (ARDS) is a syndrome of acute lung injury
      that is characterized by noncardiogenic pulmonary edema and severe hypoxemia
      second to a pathogenic impairment of gas exchange. Despite significant advances
      in the area, mortality remains high among ARDS patients. High mortality and a
      limited spectrum of therapeutic options have left clinicians searching for
      alternatives, spiking interest in selective pulmonary vasodilators (SPVs).
      Despite the lack of robust evidence, SPVs are commonly employed for their
      therapeutic role in improving oxygenation in patients who have developed
      refractory hypoxemia in ARDS. While inhaled epoprostenol (iEPO) also impacts
      arterial oxygenation by decreasing ventilation-perfusion (V/Q) mismatching and
      pulmonary shunt flow, this effect is not different from inhaled nitric oxide
      (iNO). The most effective and safest dose for yielding a clinically significant
      increase in PaO2 and reduction in pulmonary artery pressure (PAP) appears to be
      20-30 ng/kg/min in adults and 30 ng/kg/min in pediatric patients. iEPO appears to
      have a ceiling effect above these doses in which no additional benefit may be
      derived. iNO and iEPO have shown similar efficacy profiles; however, they differ
      with respect to cost and ease of therapeutic administration. The most beneficial
      effects of iEPO have been seen in adult patients with secondary ARDS as compared
      with primary ARDS, most likely due to the difference in etiology of the two
      disease states, and in patients suffering from baseline right ventricular heart
      failure. Although iEPO has demonstrated improvements in hemodynamic parameters
      and oxygenation in ARDS patients, due to the limited number of randomized
      clinical trials and the lack of studies investigating mortality, the use of iEPO
      cannot be recommended as standard of care in ARDS. iEPO should be reserved for
      those refractory to traditional therapies. 

PMID- 26294419
TI  - Reconstruction of hypopharyngeal non-circumferential defects with a submental
      island flap after hypopharyngeal carcinoma ablation, our experience of 13 cases.

PMID- 26294420
TI  - The size-brightness correspondence: evidence for crosstalk among aligned
      conceptual feature dimensions.
AB  - The same core set of cross-sensory correspondences connecting stimulus features
      across different sensory channels are observed, regardless of the modality of the
      stimulus with which the correspondences are probed. This observation suggests
      that correspondences involve modality-independent representations of aligned
      conceptual feature dimensions and predicts a size-brightness correspondence in
      which smaller is aligned with brighter. This suggestion accommodates cross
      sensory congruity effects where contrasting feature values are specified verbally
      rather than perceptually (e.g., where the words WHITE and BLACK interact with the
      classification of high- and low-pitch sounds). Experiment 1 brings these two
      issues together in assessing a conceptual basis for correspondences. The names of
      bright/white and dark/black substances were presented in a speeded brightness
      classification task, in which the two alternative response keys differed in size.
      A size-brightness congruity effect was confirmed, with substance names classified
      more quickly when the relative size of the response key needing to be pressed was
      congruent with the brightness of the named substance (e.g., when yoghurt was
      classified as a bright substance by pressing the smaller of two keys). Experiment
      2 assesses the proposed conceptual basis for this congruity effect by requiring
      the same named substances to be classified according to their edibility (with all
      of the bright/dark substances having been selected for their
      edibility/inedibility, respectively). The predicted absence of a size-brightness
      congruity effect, along with other aspects of the results, supports the proposed
      conceptual basis for correspondences and speaks against accounts in which
      modality-specific perceptuomotor representations are entirely responsible for
      correspondence-induced congruity effects. 

PMID- 26294421
TI  - Identification of residues in ABCG2 affecting protein trafficking and drug
      transport, using co-evolutionary analysis of ABCG sequences.
AB  - ABCG2 is an ABC (ATP-binding cassette) transporter with a physiological role in
      urate transport in the kidney and is also implicated in multi-drug efflux from a
      number of organs in the body. The trafficking of the protein and the mechanism by
      which it recognizes and transports diverse drugs are important areas of research.
      In the current study, we have made a series of single amino acid mutations in
      ABCG2 on the basis of sequence analysis. Mutant isoforms were characterized for
      cell surface expression and function. One mutant (I573A) showed disrupted
      glycosylation and reduced trafficking kinetics. In contrast with many ABC
      transporter folding mutations which appear to be 'rescued' by chemical chaperones
      or low temperature incubation, the I573A mutation was not enriched at the cell
      surface by either treatment, with the majority of the protein being retained in
      the endoplasmic reticulum (ER). Two other mutations (P485A and M549A) showed
      distinct effects on transport of ABCG2 substrates reinforcing the role of TM
      helix 3 in drug recognition and transport and indicating the presence of
      intracellular coupling regions in ABCG2. 

PMID- 26294424
TI  - Stewing in Not-So-Good Juices: Interactions of Skeletal Muscle With Adipose
      Secretions.

PMID- 26294422
TI  - Cardiac Resynchronization Therapy Reduces Subcellular Heterogeneity of Ryanodine
      Receptors, T-Tubules, and Ca2+ Sparks Produced by Dyssynchronous Heart Failure.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) is a major advance for
      treatment of patients with dyssynchronous heart failure (DHF). However, our
      understanding of DHF-associated remodeling of subcellular structure and function
      and their restoration after CRT remains incomplete. METHODS AND RESULTS: We
      investigated subcellular heterogeneity of remodeling of structures and proteins
      associated with excitation-contraction coupling in cardiomyocytes in DHF and
      after CRT. Three-dimensional confocal microscopy revealed subcellular
      heterogeneity of ryanodine receptor (RyR) density and the transverse tubular
      system (t-system) in a canine model of DHF. RyR density at the ends of lateral
      left ventricular cardiomyocytes was higher than that in cell centers, whereas the
      t-system was depleted at cell ends. In anterior left ventricular cardiomyocytes,
      however, we found a similar degree of heterogeneous RyR remodeling, despite
      preserved t-system. Synchronous heart failure was associated with marginal
      heterogeneity of RyR density. We used rapid scanning confocal microscopy to
      investigate effects of heterogeneous structural remodeling on calcium signaling.
      In DHF, diastolic Ca(2+) spark density was smaller at cell ends versus centers.
      After CRT, subcellular heterogeneity of structures and function was reduced.
      CONCLUSIONS: RyR density exhibits remarkable subcellular heterogeneity in DHF.
      RyR remodeling occurred in lateral and anterior cardiomyocytes, but remodeling of
      t-system was confined to lateral myocytes. These findings indicate that different
      mechanisms underlie remodeling of RyRs and t-system. Furthermore, we suggest that
      ventricular dyssynchrony exacerbates subcellular remodeling in heart failure. CRT
      efficiently reduced subcellular heterogeneity. These results will help to explain
      remodeling of excitation-contraction coupling in disease and restoration after
      CRT.

PMID- 26294425
TI  - SIRT3 Directs Carbon Traffic in Muscle to Promote Glucose Control.

PMID- 26294426
TI  - A Dash of Salt-Inducible Kinase 1 Keeps Insulin Levels in Check.

PMID- 26294427
TI  - Diabetic Nephropathy: Emerging Biomarkers for Risk Assessment.

PMID- 26294428
TI  - New Insights on the Role of SERCA During Vessel Remodeling in Metabolic Syndrome.

PMID- 26294430
TI  - Erratum. Exercise Effects on White Adipose Tissue: Beiging and Metabolic
      Adaptations. Diabetes 2015;64:2361-2368.

PMID- 26294431
TI  - Erratum. Blood and Islet Phenotypes Indicate Immunological Heterogeneity in Type
      1 Diabetes. Diabetes 2014;63:3835-3845.

PMID- 26294429
TI  - GLP-1 Cleavage Product Reverses Persistent ROS Generation After Transient
      Hyperglycemia by Disrupting an ROS-Generating Feedback Loop.
AB  - The assumption underlying current diabetes treatment is that lowering the level
      of time-averaged glucose concentrations, measured as HbA1c, prevents
      microvascular complications. However, 89% of variation in risk of retinopathy,
      microalbuminuria, or albuminuria is due to elements of glycemia not captured by
      mean HbA1c values. We show that transient exposure to high glucose activates a
      multicomponent feedback loop that causes a stable left shift of the glucose
      concentration-reactive oxygen species (ROS) dose-response curve. Feedback loop
      disruption by the GLP-1 cleavage product GLP-1(9-36)(amide) reverses the
      persistent left shift, thereby normalizing persistent overproduction of ROS and
      its pathophysiologic consequences. These data suggest that hyperglycemic spikes
      high enough to activate persistent ROS production during subsequent periods of
      normal glycemia but too brief to affect the HbA1c value are a major determinant
      of the 89% of diabetes complications risk not captured by HbA1c. The phenomenon
      and mechanism described in this study provide a basis for the development of both
      new biomarkers to complement HbA1c and novel therapeutic agents, including GLP
      1(9-36)(amide), for the prevention and treatment of diabetes complications. 

PMID- 26294433
TI  - Comment on Pellegrinelli et al. Human Adipocytes Induce Inflammation and Atrophy
      in Muscle Cells During Obesity. Diabetes 2015;64:3121-3134.

PMID- 26294435
TI  - Comment on Rickels et al. Loss-of-Function Mutations in ABCA1 and Enhanced beta
      Cell Secretory Capacity in Young Adults. Diabetes 2015;64:193-199.

PMID- 26294437
TI  - Comment on Faerch et al. GLP-1 Response to Oral Glucose Is Reduced in
      Prediabetes, Screen-Detected Type 2 Diabetes, and Obesity and Influenced by Sex:
      The ADDITION-PRO Study. Diabetes 2015;64:2513-2525.

PMID- 26294439
TI  - Comment on Sharma. Mitochondrial Hormesis and Diabetic Complications. Diabetes
      2015;64:663-672.

PMID- 26294441
TI  - Multivalent linkers for improved covalent binding of oligonucleotides to dye
      doped silica nanoparticles.
AB  - This paper describes the fabrication of oligonucleotide-coated Cy5-doped silica
      nanoparticles using a combination of multivalent linkers and their use in surface
      based DNA sandwich hybridization assays. Dipodal silane is introduced as a means
      to fabricate amine-coated silica nanoparticles and its advantages compared to
      monopodal silanes are discussed. The use of dipodal silane in conjunction with
      three different polymer linkers (oxidized dextran, linear and 8-arm polyethylene
      glycol (PEG)) to immobilize single-stranded DNA to Cy5-doped nanoparticles is
      investigated and dynamic light scattering measurements and Fourier transform
      infrared spectroscopy are used to follow the progression of the functionalization
      of the nanoparticles. We observe a significant improvement in the binding
      stability of the single-stranded DNA when the dipodal silane and 8-arm PEG are
      used in combination, when compared to alternative conjugation strategies. Both
      8mer and 22mer oligonucleotides are securely conjugated to the high-brightness
      nanoparticles and their availability to hybridize with a complementary strand is
      confirmed using solution-based DNA hybridization experiments. In addition, a full
      surface-based sandwich assay demonstrates the potential these nanoparticles have
      in the detection of less than 500 femtomolar of a DNA analogue of micro RNA, miR
      451. 

PMID- 26294442
TI  - Runtastic PRO app: an excellent all-rounder for logging fitness.

PMID- 26294443
TI  - Effects of regular physical exercise training in adults with chronic kidney
      disease (PEDro synthesis).

PMID- 26294444
TI  - Consensus on the criteria needed for creating a rare-disease patient registry. A
      Delphi study.
AB  - BACKGROUND: Patient registries (PRs) are important tools for public-health
      surveillance and rare-disease research. The purpose of this study is to identify
      the most important criteria for the creation of a rare-disease PR that could be
      used by public-health authorities to develop health policies. METHODS: A
      consensus-development Delphi study was used, with participants selected for their
      expertize in rare diseases and registries. Participants were asked to complete a
      questionnaire on the most important criteria for creating PRs. Three rounds were
      performed. RESULTS: Agreement was reached on half the questions in the first
      round and on 89% of questions in the final round, with a total expert
      participation rate of around 60% by the final stage. This study made it possible
      to reach a broader consensus starting from experts' initial assessment of the
      features that should be considered for the creation of a rare-disease PR.
      CONCLUSION: The consensus method used made it possible to define the
      characteristics of a PR based on expert opinion within a rare-disease framework.
      This study may serve as a guide for helping other researchers plan and build a
      rare-disease PR.

PMID- 26294446
TI  - Usability of PDF based Digital Textbooks to the Physically Disabled University
      Student.
AB  - Digital textbooks have been expected for providing multimedia information that
      the print textbooks could not handle. The original digital textbook can be
      fabricated relatively easily by using Epub or DAISY. Print textbooks are,
      however, employed as textbooks in the most of lectures in universities.
      Therefore, it is considered necessary to convert the content of the print
      textbook to the digital textbook simply and in a short time. In this paper, the
      digital textbook using PDF files of the print textbook was suggested as one of
      simple and practical solution to provide an alternative textbook for the
      physically disabled university student who has difficulty handling the print
      textbook. Then usability of the suggested method was evaluated experimentally
      from the point of workload. Result of the experiment indicates that the digital
      textbook fabricated as the alternative one for the print textbook by the
      suggested method has a potential to reduce workload for the physically disabled
      university students. In addition, the digital textbook with larger LCD display
      needs less workload than the print textbook. Then, there are not so much
      difference in the workload between the print book which is smaller than the print
      textbook and the digital book made from the print book. 

PMID- 26294447
TI  - Paper-Based Textbooks with Audio Support for Print-Disabled Students.
AB  - Utilizing invisible 2-dimensional codes and digital audio players with a 2
      dimensional code scanner, we developed paper-based textbooks with audio support
      for students with print disabilities, called "multimodal textbooks." Multimodal
      textbooks can be read with the combination of the two modes: "reading printed
      text" and "listening to the speech of the text from a digital audio player with a
      2-dimensional code scanner." Since multimodal textbooks look the same as regular
      textbooks and the price of a digital audio player is reasonable (about 30 euro),
      we think multimodal textbooks are suitable for students with print disabilities
      in ordinary classrooms. 

PMID- 26294448
TI  - ICT Learning Technologies for Disabled People: Recommendations for Good Practice.
AB  - The use of ICT in education is becoming increasingly important and has potential
      advantages to disabled learners if the technologies are appropriately designed,
      including for accessibility and usability, and used. This paper presents the
      first sets of recommendations for learning technologies for disabled people aimed
      at disabled learners, teachers, developers and educational institutions
      respectively. They were developed as part of the work of the Enable Network for
      ICT Learning for Disabled People and involved input from both experts and end
      users. The concise format facilitates production in a variety of formats and
      languages for accessibility and wide distribution. The paper discusses the
      recommendations and their relationship to existing guidelines. 

PMID- 26294449
TI  - Supporting Blind Students in STEM Education in Austria.
AB  - Equal access to education will foster a knowledge society for all. In particular
      for the ICT based information society a benchmark has been set to raise the
      numbers of graduates in science, technology, engineering and mathematics (STEM)
      study courses by 15% (748.000) per year, asking for increased efforts in Europe
      (http://ec.europa.eu/education/policy/strategic-framework/index_en.htm). This
      holds even more true for people with disabilities who a) participate in and
      graduate from STEM at a much lower number and b) face a much higher unemployment
      rate, in particular in STEM related fields. This asks for sound and well-founded
      education - first and foremost in math - for people with disability and here
      especially for blind people. 

PMID- 26294450
TI  - A network of peers and practices for addressing Learner Variability: UDLnet.
AB  - Grounded on new research in neuroscience and the Design for All principles,
      Universal Design for Learning (UDL) constitutes an educational approach that
      promotes access, participation and progress in the general curriculum for all
      learners. The difficulty is in all cases translating the UDL principles and
      guidelines into practice. Though the UDL policy context supports a shift to
      inclusion, professionals need more support to develop their practice. In order to
      bridge the gap between policies and practice the UDLnet network aspires to
      address this necessity collecting and creating good practices under the framework
      of Universal Design for Learning. This paper presents the UDLnet project, its
      aims, the methodological framework, as well as the envisaged themes. UDLnet is a
      European network that aims to contribute to the improvement of teachers' practice
      in all areas of their work, combining ICT skills with UDL-based innovations in
      pedagogy, curriculum, and institutional organization. 

PMID- 26294451
TI  - Innovative methods and tools for professionals working in supported living
      services for intellectually disabled persons.
AB  - Autonomy of mid-seriously and seriously intellectually disabled persons is
      encouraged both by legislations on human rights and the modern social care and
      services. The process leading to the maximum possible autonomy is illustrated by
      a developmental spiral in our model. Specialty of the development is that the
      personal educational projects are realized during everyday activities. The
      process requires conscious professionals with an empowering and motivating
      attitude, with adult relationship to the intellectually disabled persons and
      versatile skills and tools. In this educational relationship the social
      professional and the supported person are equal partners moving together along
      the spiral of human development. An innovative tool-battery has been developed
      aiding support-staff in the 'pedagogical' task embedded into everyday social
      services. The tool-battery and its first application in supported living services
      of the Hungarian Down Foundation are introduced in this paper. 

PMID- 26294452
TI  - Evidence-based development and first usability testing of a social serious game
      based multi-modal system for early screening for atypical socio-cognitive
      development.
AB  - At current, screening for, and diagnosis of, autism spectrum disorders (ASD) are
      based on purely behavioral data; established screening tools rely on human
      observation and ratings of relevant behaviors. The research and development
      project in the focus of this paper is aimed at designing, creating and evaluating
      a social serious game based multi-modal, interactive software system for
      screening for high functioning cases of ASD at kindergarten age. The aims of this
      paper are (1) to summarize the evidence-based design process and (2) to present
      results from the first usability test of the system. Game topic, candidate
      responses, and candidate game contents were identified via an iterative
      literature review. On this basis, the 1<sup>st</sup> partial prototype of the
      fully playable game has been created, with complete data recording functionality
      but without the decision making component. A first usability test was carried out
      on this prototype (n=13). Overall results were unambiguously promising. Although
      sporadic difficulties in, and slightly negative attitudes towards, using the game
      occasionally arose, these were confined to non-target-group children only. The
      next steps of development include (1) completing the game design; (2) carrying
      out first large-n field test; (3) creating the first prototype of the decision
      making component. 

PMID- 26294454
TI  - Applicability of standard eye-tracking technique in people with intellectual
      disability: methodological conclusions from a series of studies.
AB  - Although considerable amount of evidence suggest that info-communication
      technologies have important potential to promote higher level of adaptive
      functioning and more efficient learning in people with intellectual disability
      (ID), very little is known about how people with ID scan visually the visual user
      interfaces of digital tools. Eye-tracking technique is widely used to study
      visual scanning processes and is used more and more extensively in assistive and
      educational technologies, too. Therefore, it is important to explore and
      understand the limitations and potentials of applying eye-tracking technique in
      people with ID. The present paper aims this by analyzing data from 4 studies
      (n=38/38 and n=15/30), via contrasting data from people with ID with data from
      neurotypical (NT) control subjects along 3 variables, indicative of the
      applicability of eye-tracking technique. Results strongly suggest that there are
      specific difficulties in using eye-tracking in people with ID, showing
      considerable individual variability but depending also on the nature of the
      actual task. Consequentially, using eye-tracking in this group expectedly
      requires special considerations and specific solutions. 

PMID- 26294453
TI  - Evidence-based development and evaluation of mobile cognitive support apps for
      people on the autism spectrum: methodological conclusions from two R+D projects.
AB  - A growing body of evidence confirms that mobile digital devices have key
      potentials as assistive/educational tools for people with autism spectrum
      disorders. The aim of this paper is to outline key aspects of development and
      evaluation methodologies that build on, and provide systematic evidence on
      effects of using such apps. We rely on the results of two R+D projects, both
      using quantitative and qualitative methods to support development and to evaluate
      developed apps (n=54 and n=22). Analyzing methodological conclusions from these
      studies we outline some guidelines for an 'ideal' R+D methodology but we also
      point to important trade-offs between the need for best systematic evidence and
      the limitations on development time and costs. We see these trade-offs as a key
      issue to be resolved in this field. 

PMID- 26294455
TI  - Developing an Animal Counting Game in Second Life for a Young Adult with Down
      Syndrome.
AB  - Down syndrome is caused by trisomy of all or part of human chromosome 21 (HSA21)
      and is the most common genetic cause of significant intellectual disability. It
      is the most common chromosome abnormality in humans, occurring in about one per
      1000 babies born each year. It is typically associated with physical growth
      delays, characteristic facial features, and mild to moderate intellectual
      disability [1]. The average IQ of a young adult with Down syndrome is 50,
      equivalent to the mental age of an 8- or 9-year-old child, but this varies widely
      [2]. The purpose of this study is to create a tool in the virtual world Second
      Life [3] to develop basic counting skills for young adults with Down syndrome.
      Following an international literature review, our project explored and used pre
      programmed equipment, Linden Scripting Language, tables and intellectual
      interfaces with educational intentions. The study suggests that the product will
      not only aid the development of counting skills for young adults with Down
      syndrome, but will also create an entertaining environment for all visitors,
      furthermore promoting imagination and motivation within a virtual community. 

PMID- 26294456
TI  - Delivering beneficial impacts in Assistive Technology: Improving government's
      approach to innovation.
AB  - Society typically relies on the industrial sector to supply product and service
      innovations through the free market system. In some areas of free market failure
      deemed important to society - such as Assistive Technology - governments
      intervene by applying alternative innovation systems. This paper contends that
      governments consistently and inappropriately support an exploratory grant
      approach led by academia which generates knowledge in conceptual and prototype
      states, and instead should shift to a procurement contract approach led by
      industry which designs, tests and deploys commercial products and services. 

PMID- 26294457
TI  - Cost-effectiveness of powered wheelchairs: findings of a study.
AB  - This study surveyed a sample of 79 wheelchair users who had obtained powered
      wheelchairs from the National Health Service in an Italian Region in the period
      2008-2013. The wheelchair prescriptions had been done on the basis of an
      assessment protocol agreed with the Local Health Authority. Follow-up interviews
      were carried out at the users' homes, in order to collect information about the
      wheelchair use and its effectiveness, usefulness and economic impact. The
      instruments used in the interviews included an introductory questionnaire
      (describing the wheelchair use), the QUEST (measuring the user's satisfaction),
      the PIADS (measuring the psychosocial impact, in terms of perceived changes in
      ability, adaptability and self-esteem), the FABS/M (detecting environmental
      facilitators and barriers) and the SCAI (estimating the economic impact).
      Overall, positive outcomes were detected for most users, especially in relation
      to their satisfaction and the psychosocial impact. A number of barriers were
      identified in various settings (at home, in public places, in natural spaces, in
      public transportation) that sometimes restrict the user mobility and thus may
      claim for corrective actions. Several environmental factors acting as
      facilitators were also identified. In relation to the economic impact, the
      provision of a powered wheelchair generated remarkable savings in social costs
      for most of the users, on average about 36.000 Euros per person on a projected 5
      years span. This estimate results from the comparison between the social cost of
      the intervention (sum of the costs of all material and human resources involved
      in the provision and usage of the wheelchair) and the cost of non-intervention
      (the presumed social cost incurred in case no powered wheelchair had been
      provided and the user had to carry on with just a manual wheelchair). The study
      was also an opportunity to develop and try out a follow-up method that proved
      applicable within service delivery practice. 

PMID- 26294458
TI  - Comparing three knowledge communication strategies - Diffusion, Dissemination and
      Translation - through randomized controlled studies.
AB  - This paper describes a series of three randomized controlled case studies
      comparing the effectiveness of three strategies for communicating new research
      based knowledge (Diffusion, Dissemination, Translation), to different Assistive
      Technology (AT) stakeholder groups. Pre and post intervention measures for level
      of knowledge use (unaware, aware, interested, using) via the LOKUS instrument,
      assessed the relative effectiveness of the three strategies. The latter two
      approaches were both more effective than diffusion but also equally effective.
      The results question the value added by tailoring research findings to specific
      audiences, and instead supports the critical yet neglected role for relevance in
      determining knowledge use by stakeholders. 

PMID- 26294459
TI  - Testing usability of Mobile Shower Commodes for adults with Spinal Cord Injury:
      research method and overview.
AB  - This paper provides an overview of research to develop a new questionnaire
      testing mobile shower commode usability. It describes the methodology used to
      develop the questionnaire, and reports significant findings that have been
      published in peer-reviewed journals. Implications of the research and
      recommendations for further research on mobile shower commode usability are
      discussed. 

PMID- 26294460
TI  - Level Of Knowledge Use Survey (LOKUS): A validated instrument for tracking
      knowledge uptake and use.
AB  - Researchers working in fields intending to generate beneficial socio-economic
      impacts are increasingly challenged to demonstrate evidence that the findings
      from their studies have value to audiences beyond the peer academic community.
      These diverse and diffuse target audiences may include clinicians, consumers,
      manufacturers and information brokers. This paper summarizes a project that
      designed, constructed and validated a web-based instrument for collecting and
      analyzing self-reported data on knowledge use. The Level Of Knowledge Use Survey
      instrument is valid and reliable for measuring uptake of new knowledge and for
      tracking changes in level of knowledge use over time. 

PMID- 26294461
TI  - The Cooperate Assistive Teamwork Environment for Software Description Languages.
AB  - Versatile description languages such as the Unified Modeling Language (UML) are
      commonly used in software engineering across different application domains in
      theory and practice. They often use graphical notations and leverage visual
      memory for expressing complex relations. Those notations are hard to access for
      people with visual impairment and impede their smooth inclusion in an engineering
      team. Existing approaches provide textual notations but require manual
      synchronization between the notations. This paper presents requirements for an
      accessible and language-aware team work environment as well as our plan for the
      assistive implementation of Cooperate. An industrial software engineering team
      consisting of people with and without visual impairment will evaluate the
      implementation. 

PMID- 26294462
TI  - Are mainstream mobile technologies bringing about new opportunities for people
      with disabilities? Insights from three case studies.
AB  - The market of mobile technologies has considerably increased in the past few
      years and the costs have consequently decreased. This rapid technological
      evolution can be seen in two different ways from the perspective of people with
      disability: on the one side it represents a great opportunity to create new
      solutions for improving independence; on the other it may represent a source of
      social exclusion if appropriate assistive solutions are not available to make
      technology usable by people with disability. This paper describe three case
      studies of persons with disabilities that have undergone an Assistive Technology
      assessment at the DAT service of Fondazione Don Gnocchi (Milan, Italy) involving
      the use of mobile ICT based Assistive Technologies. In all the three cases the
      appropriate solution for performing the desired activities is represented by a
      combination of mainstream products and assistive products. The three use cases
      described support the idea that mobile technologies can be powerful and versatile
      instruments to create assistive solutions for improving independence in daily
      life. 

PMID- 26294463
TI  - Can We Fix The Web?
AB  - This paper reports on an innovative approach to facilitating the expedient
      reporting of web accessibility issues using volunteers. The aim of the Fix the
      Web website and project is not to replace existing formal methods of reporting
      inaccessible websites, but to provide an easy, informal way by which users with
      disabilities can report inaccessible websites quickly and can be assured that a
      volunteer on their behalf will take the issue up with the website owner or
      administrator. Fix the Web was launched in 2010 and from a small start has gone
      onto success in dealing with nearly 150 inaccessible websites. The results of an
      analysis of reports of inaccessible websites received by the Fix the Web are also
      presented and the practical benefits and limitations of using an informal
      approach to achieve accessibility are discussed. 

PMID- 26294464
TI  - Better Questions, Better Answers: Structured Web Accessibility Evaluations for
      Non-Experts.
AB  - Large scale benchmarking of web accessibility can benefit from human input to
      complement results produced by automatic evaluation tools. This paper presents a
      novel method that enables non-experts to provide input on web accessibility. The
      semi-automatic approach guides the evaluators through a structured process with
      clear instructions. We present a template to describe different types of user
      input and an outline of the empirical validation. 

PMID- 26294465
TI  - Accessible Web Design - The Power of the Personal Message.
AB  - The aim of this paper is to describe ongoing research being carried out to enable
      people with visual impairments to communicate directly with designers and
      specifiers of hobby and community web sites to maximise the accessibility of
      their sites. The research started with an investigation of the accessibility of
      community and hobby web sites as perceived by a group of visually impaired end
      users. It is continuing with an investigation into how to best to communicate
      with web designers who are not experts in web accessibility. The research is
      making use of communication theory to investigate how terminology describing
      personal experience can be used in the most effective and powerful way. By
      working with the users using a Delphi study the research has ensured that the
      views of the visually impaired end users is successfully transmitted. 

PMID- 26294466
TI  - Smart Houses and Uncomfortable Homes.
AB  - In order for smart houses to achieve acceptance from potential beneficiaries they
      will need to match the users' expectation that their house is also their home,
      with the sense of privacy and control that this implies. Designers of this
      technology will need to be aware of findings in this regard from fields such as
      architecture and design ethnography. 

PMID- 26294467
TI  - A plug&play Brain Computer Interface solution for AAL systems.
AB  - We present a complete BCI-enabled (Brain Computer Interface) solution for Ambient
      Assisted Living system control. BCI are alternative, augmentative communication
      means capable of exploiting just the brain waveforms to infer intent, thus
      potentially posing as a technological bridge capable of overcoming limitations in
      the usual neuromuscular pathways. The module was completely developed in a
      customized way, encompassing hardware and software components. We demonstrate the
      effectiveness of the approach on a practical control scenario in which the user
      can issue 4 different commands, at his own pace and will, in real-time. No
      initial calibration is necessary, in line with the aimed plug&play approach.
      Results are very promising, especially in false positives rejection, well
      improving over literature. 

PMID- 26294468
TI  - Open Ambient Intelligence Environments.
AB  - The present impact of ambient intelligence concepts in eInclusion is first
      briefly reviewed. Suggestions and examples of how ambient intelligent
      environments should be specified, designed and used to favour independent living
      of people with activity limitations are presented. 

PMID- 26294469
TI  - BRIDGeViz: Towards an Interactive Data Visualization Tool for Exploration of
      Indoor Daily Life of an Older Adult.
AB  - Interactive data visualization could be beneficial to gain insight into the data
      concerning the inhabitant and the environment collected by an ambient assisted
      living system. In this paper we present BRIDGeViz that is a web-based interactive
      visualization tool for the BRIDGe AAL system. It is an effort to help caregivers,
      the main target users, to explore the daily life dynamics of the inhabitant in
      order to detect life trends, deviation from daily norms, and search for potential
      causes of a problem. BRIDGeViz provides two main views and visualizations: the
      overview visualization for a holistic view of long-term data and the detailed
      view for a day-level detailed exploration. The visualizations are enriched by
      interaction mechanisms and some analytic support such as searching for similar
      days. We also conducted a user study with a demo version of our tool with a
      positive overall feedback. 

PMID- 26294470
TI  - Assessing User Needs and Requirements for Assistive Robots at Home.
AB  - 'Robots in healthcare' is a very trending topic. This paper gives an overview of
      currently and commonly used methods to gather user needs and requirements in
      research projects in the field of assistive robotics. Common strategies between
      authors are presented as well as examples of exceptions, which can help future
      researchers to find methods suitable for their own work. Typical problems of the
      field are discussed and partial solutions are proposed. 

PMID- 26294471
TI  - Designing an Assistive Learning Aid for Writing Acquisition: A Challenge for
      Children with Dyslexia.
AB  - In Pakistan, the biggest challenge is to provide high quality education to the
      individuals with learning disabilities. Besides the well known affordance issue,
      there is a lack of awareness regarding the term dyslexia and remedial teaching
      training that causes the identification as well as remediation of the dyslexic
      individuals at early stages in Pakistan. The research was focused to exploit the
      benefits of using the modern mobile technology features in providing a learning
      platform for young dyslexic writers. Based on potential usability requirements of
      young dyslexic writers stated by remedial teachers of dyslexics, an android based
      application is designed and implemented using the usability engineering process
      model to encourage the learning process and help dyslexic children improve their
      fundamental handwriting skill. In addition, a handwriting learning algorithm
      based on concepts of machine learning is designed and implemented to decide the
      learning content, evaluate the learning performance, display the performance
      results and record the learning growth to show the strengths and weaknesses of a
      dyslexic child. The research was also aimed to assess the usability of the
      learner-centered application by the targeted population by conducting a user
      acceptance test to evaluate their learning experience and benefits of the
      developed application to dyslexic users. The results of the evaluation provided
      by the participants revealed that application has potential benefits to foster
      the learning process and help children with dyslexia by improving their
      foundational writing skills. 

PMID- 26294472
TI  - Using a Participatory Action Research Design to Develop an Application Together
      with Young Adults with Spina Bifida.
AB  - INTRODUCTION: Young adults with spina bifida often have cognitive difficulties.
      As a result, young adults with disabilities are facing challenges with respect to
      housing, education, relationships and vocation which increases risk of
      unemployment. AIM: The aim is to describe a method to develop a smartphone
      application together with young adults with spina bifida as an assistive
      technology for cognition. METHOD: In a Participatory Action Research approach,
      young adults (n = 5) with spina bifida were individually interviewed with
      Canadian Occupational Performance Measure (COPM). The participants' restrictions
      in everyday life activities, identified by COPM, were discussed in a focus group
      formed by the young adults and the result was analyzed using qualitative content
      analysis. Developing the application the principles of Human-Centered-Design and
      Universal Design was followed. RESULT: An application made for iOS with a focus
      on usability and worthiness, done by creating a clear and intuitive interface,
      with a calendar function useful for example to initiate and plan social
      activities was developed. CONCLUSION: The method seems useful when the outcome
      from the project, a beta version of an application for iOS Smartphone, was
      achieved in agreement with the participants. The study highlight the importance
      of involving individuals with disabilities when developing smartphone
      applications.

PMID- 26294473
TI  - Conceptual Design of Haptic-Feedback Navigation Device for Individuals with
      Alzheimer's Disease.
AB  - Wayfinding ability in older adults with Alzheimer's disease (AD) is progressively
      impaired due to ageing and deterioration of cognitive domains. Usually, the sense
      of direction is deteriorated as visuospatial and spatial cognition are associated
      with the sensory acuity. Therefore, navigation systems that support only visual
      interactions may not be appropriate in case of AD. This paper presents a concept
      of wearable navigation device that integrates the haptic-feedback technology to
      facilitate the wayfinding of individuals with AD. The system provides the
      simplest instructions; left/right using haptic signals, as to avoid users'
      distraction during navigation. The advantages of haptic/tactile modality for
      wayfinding purpose based on several significant studies are presented. As
      preliminary assessment, a survey is conducted to understand the potential of this
      design concept in terms of (1) acceptability, (2) practicality, (3) wearability,
      and (4) environmental settings. Results indicate that the concept is highly
      acceptable and commercially implementable. A working prototype will be developed
      based on the results of the preliminary assessment. Introducing a new method of
      navigation should be followed by continuous practices for familiarization
      purpose. Improved navigability allows the good performance of activities of daily
      living (ADLs) hence maintain the good quality of life in older adults with AD. 

PMID- 26294474
TI  - Applying guidelines for evaluating digital technologies for people living with
      dementia: A case study.
AB  - Affordable solutions are needed to offer the growing population of people
      diagnosed with dementia support to maintain independence. Assistive technology
      has the potential to address this issue but devices should be tailored to the
      needs of this population. Previous work has focused on the design of such
      technologies and in new work evaluation (trial) guidelines are proposed to offer
      consistency amongst researchers looking to test completed products with intended
      users. The guidelines are implemented as trial protocol guidance and are applied
      to an existing protocol as a case example of how the guidelines could be used.
      Differences between the protocol and the guidelines are highlighted and provide
      evidence as to the potential usefulness of the document in informing an
      evaluation. The need for further development of the guidelines is also discussed
      and the authors state their intention to collaborate internationally in order to
      evolve the framework to the stage where it can be published as an accessible
      resource. 

PMID- 26294475
TI  - Persons with Dementia and Their Caregivers Using GPS.
AB  - The aim of the study is to generate knowledge on the use of Global Positioning
      Systems (GPS) to support autonomy and independence for persons with dementia. By
      studying a larger cohort of persons with dementia (n=208) and their caregivers,
      this study provides essential knowledge for planning and implementing GPS
      technology as a part of public health care services. Commercially available GPS
      technology was provided to the cohort of 208 persons with dementia from nineteen
      different Norwegian municipalities. The participants used GPS when performing
      outdoor activities as part of their daily life during a period of time between
      2012 and 2014. Their family caregivers were instructed on how to use the GPS
      technology for locating the participants. The study documents that using GPS for
      locating persons with dementia provide increased safety for the person with
      dementia, their family caregivers and their professional caregivers. Furthermore
      the results confirm that by using GPS, persons with dementia may maintain their
      autonomy, enjoy their freedom and continue their outdoor activities despite the
      progression of the disease. Preconditions for successful implementation are that
      health professionals are trained to assess the participant's needs, that ethical
      dilemmas are considered, that caregivers have adequate knowledge about using the
      technology and that procedures and routines for administrating the GPS and
      locating persons with dementia are established. Early intervention and close
      collaboration between persons with dementia, family caregivers and professional
      caregivers are important for successful implementation of GPS in public health
      care. 

PMID- 26294476
TI  - Guidelines and Options for Computer Access from a Reclined Position.
AB  - Many people can benefit from working in a reclined position when accessing a
      computer. This can be due to disabilities involving musculoskeletal weakness, or
      the need to offload pressure on the spine or elevate the legs. Although there are
      "reclining workstations" on the market that work for some people, potentially
      better solutions tailored to individual needs can be configured at modest cost by
      following some basic principles. 

PMID- 26294477
TI  - Stepwise Approach to Accessible MOOC Development.
AB  - Developing resources for online learning in its many guises and more recently for
      MOOCs has been discussed across the educational sector, usually by individuals
      working for one institution or organisation. Rarely are there discussions that
      highlight the issues of collaborative working on content that is delivered over a
      period of weeks for a wide range of abilities and skills. In particular there is
      a reluctance to face the issues presented by barriers to access for those with
      disabilities and even the issues that could arise should an academic be unable to
      access the development platform to present content. This paper aims to approach
      these issues by providing guidance in a series of practical steps that highlight
      an inclusive design approach. 

PMID- 26294478
TI  - DigiPlace4all: an online peer support community for digital skills.
AB  - The DigiPlace4all online peer support community supports people with disabilities
      in developing digital literacy skills needed to transition from Vocational and
      Educational Training (VET) to mainstream education & employment. It facilitates
      the development of informal one-to-one peer support relationships between members
      who can post and respond to requests and offers of peer support and share
      information on a range of associated topics. It is active in Ireland, Belgium,
      Poland and Bulgaria and is being spread internationally. 

PMID- 26294479
TI  - Maximizing Employment Outcomes through the Use of "Lower-Tech" Assistive
      Technology & Rehabilitation Engineering.
AB  - For many people with disabilities, Assistive Technology tools and Rehabilitation
      Engineering principles are key to successful employment outcomes. At the same
      time, employers and service providers are often under the impression that
      accommodations and AT solutions require high-tech, complicated, and expensive
      technologies. This paper discusses how creative problem solving and a "keep it
      simple" mindset can result in very functional low-cost solutions. 

PMID- 26294480
TI  - Usability of RemindMe - An Interactive Web-Based Mobile Reminder Calendar: A
      Professional's Perspective.
AB  - AIM: The aim of the study was to examine the usability of an interactive web
      based mobile reminder calendar (RemindMe) developed for supporting individuals in
      organizing, planning and executing activities in everyday life, from the
      perspectives of professionals. METHODS AND MATERIAL: Eleven professionals working
      in community services evaluated the usability of RemindMe in their clinical
      practice. Data were collected using semi-structured interviews and analysed with
      inductive qualitative analysis. RESULTS: The professionals perceived that
      RemindMe was useful, easy to use, and intuitive. There was a need among
      professionals for a web-based reminder calendar that requires the active
      acknowledgement of reminders. RemindMe's feedback system offering self-monitored
      information based on the user's interaction with the system supported the
      professionals in discussions, evaluation, and follow-up based on the needs of the
      persons with cognitive impairments. CONCLUSION: The results indicate that
      RemindMe may be potentially useful to professionals who provide support to
      individuals with cognitive impairments. However, further research is needed to
      evaluate experience of using RemindMe from the perspective of individuals with
      cognitive impairments.

PMID- 26294481
TI  - Ontology-based Semantic Support to Improve Accessibility of Graphics.
AB  - We aim to ease the process of authoring accessible graphics as well as taking a
      first step towards the long-term goal of allowing blind persons to access
      graphics autonomously. We are developing and experimenting with a hierarchical
      set of knowledge bases related to the presentation of visual objects and cues in
      the form of ontologies that will act as the formal, axiomatic underpinnings of an
      accessibility layer or, later on, a graphics reader/browser for blind and
      visually impaired people. The concept and prototypes of smart (or communicative)
      graphics [1], in which readers obtain information about the syntactic and
      semantic content through the use of e.g. a natural language interface, should be
      expanded by exploiting the benefits of formal semantics supported by domain- and
      task-aware ontologies describing the elements, visual cues and relations used for
      visualization or visual display. 

PMID- 26294482
TI  - Magnetic, Angular Rate and Gravity Sensor System Fusion for Orientation
      Estimation.
AB  - This paper presents the development of a fusion strategy to integrate and
      calibrate signals from magnetometers, gyroscopes and accelerometers to implement
      a magnetic, angular rate and gravity (MARG) sensor system. The aim of such
      algorithms is to capture signals from the individual sensors and identify,
      compensate and reduce external and internal errors such as bias, scale factor and
      drifts, which highly depend on the noise levels. The necessary calibrations to
      ensure the reliability of captured data are also presented. The orientation data
      obtained by the proposed algorithm will be compared with a commercial motion
      capture system, which are currently being used by researchers in biomechanical
      analysis and in clinical motor rehabilitation studies. 

PMID- 26294483
TI  - A Comparative Study on Java Technologies for Focus and Cursor Handling in
      Accessible Dynamic Interactions.
AB  - For an interactive application, supporting and guiding the user in fulfilling
      tasks is most important. The behavior of the application that will guide users
      through the procedures until they finish the task has to be designed intuitively
      and well guiding, especially if the users has only restricted or no access to the
      visual and spatial arrangement on the screen. Therefore, the focus/cursor
      management plays an important role for orientation and navigating through the
      interaction. In the frame of ongoing research on a software tool supporting blind
      people in more efficiently doing mathematical calculations, we researched how
      Java technologies support implementing an accessible Graphical User Interface
      (GUI) with an additional focus on usable accessibility in terms of guiding blind
      users through the process of solving mathematical calculations. We used Java
      Swing [1] and Eclipse SWT [2] APIs for creating a series of prototypes. We tested
      a) accessibility and usability of the prototypes for blind people when using
      screen reader software and refreshable Braille display and b) the implementation
      support to developers provided by both technologies. It turned out that Eclipse
      SWT API delivered best results under Windows operating system. 

PMID- 26294484
TI  - Designing GUIs for low vision by simulating reduced visual acuity: reduced
      resolution versus shrinking.
AB  - The visual uniqueness of information carrying icon and text elements has received
      little attention in the HCI research literature. The information carrying
      elements of graphical designs must be visually unique in order to be visually
      recognizable. This is increasingly important with the diversity of form factors
      and types of information displays. This paper explores two simple strategies for
      testing visual designs by simulating low visual acuity, namely by reducing the
      resolution and by shrinking. Two case studies demonstrate that low vision
      simulation by shrinking is more effective than reducing the resolution. Moreover,
      the case studies show how the low vision simulation can help identify design
      aspects that need attention. Design shrinking is not a substitute for user
      testing on actual user groups, but meant as a tool for early screening of designs
      and an aid for designers to help understand the effects of their design. The
      method can also be used as a tool for communicating design problems and
      justifying design decisions to stakeholders of a project through presentations
      and reports. 

PMID- 26294485
TI  - An Identification Procedure for Behavioral Analysis in a Multi-User environment.
AB  - As the average age of the EU population increases, ICT solutions are going to
      play a key role in order to find answers to the new challenges the demographic
      change is carrying on. At the University of Parma an AAL (Ambient Assisted
      Living) system named CARDEA has been developed during the last 10 years. Within
      CARDEA, behavioral analysis is carried out, based on environmental sensors. If
      multiple users live in the same environment, however, data coming from sensors
      need to be properly tagged: in this paper, a simple technique for such tagging is
      proposed, which exploits the same wireless transmission used for transmitting
      data, thus not requiring additional hardware components and avoiding more complex
      and expensive (radio)localization techniques. Preliminary results are shown,
      featuring a satisfactory accuracy. 

PMID- 26294486
TI  - Tele-care robot for assisting independent senior citizens who live at home.
AB  - In the last twenty years most developed countries face dramatic demographic
      changes, and predominantly the rapid aging of their population. As the share of
      elderly people is climbing while the number of care providers is declining, the
      aging problem is becoming an increasingly important social and economic
      challenge. The supply of care at home, utilizing affordable tele-care systems and
      smart home technologies, is one of the promising strategies to cope with
      challenges posed by these demographic changes. The goal of this paper is to
      present a tele-care robot (TCR) aimed to assist Senior citizens who live
      independently at their home, that need assistance in daily life activities. The
      idea of the proposed system is that a caregiver, operating from a central
      location, will be able to service between 10 to 20 patients living at their home,
      by using the tele-care robot. The robot will possess motion control capabilities
      to move inside the house of each patient and alert in case that emergency events
      occur. The robot will allow the care provider to communicate remotely with the
      patient using audio and video equipment installed on the robot. By using the
      robot, the caregiver will be able to examine several times during the day the
      well-being of the patient, his medication consumption, and his overall
      functionality. 

PMID- 26294487
TI  - Self-tuning behavioral analysis in AAL "FOOD" project pilot environments.
AB  - Behavioral analysis, based on unobtrusive monitoring through environmental
      sensors, is expected to increase health awareness of AAL systems. In this paper,
      techniques for assessing behavioral quantitative features are discussed, suitable
      for detecting behavioral anomalies in an unsupervised fashion, i.e., with no need
      of defining target reference behaviors and of tuning user-specific threshold
      parameters. Such technique is being exploited for analyzing data coming from a
      set of European pilot sites, in the framework of the EU/AAL-JP project "FOOD",
      specifically focused at kitchen activity. Simple results are illustrated,
      suitable for proof-of-concept validation. 

PMID- 26294488
TI  - Combining apps targeting professionals and senior citizens to improve housing
      accessibility and influence housing provision policies.
AB  - Two separate apps that address the increasingly important issue of accessible
      housing for senior citizens have been developed in different project settings.
      One of the apps was developed to facilitate the process for professional raters
      to assess housing accessibility in the context of individual housing adaptations.
      The other app was developed for senior citizens to raise their awareness of
      possible accessibility problems in their current dwelling and in other apartments
      within the available housing stock. Both apps were developed with a high degree
      of active user involvement in processes utilizing multiple state of the art
      methods. The results are two well accepted prototype apps perceived as user
      friendly and appropriate for the intended user groups. By combining these two
      apps, our ambition is for the professional raters to benefit by gaining knowledge
      of their clients' perceived needs and desires, and for senior citizens to benefit
      by getting access to a database of professionally rated dwellings. The ultimate
      goal is the generation of sound knowledge reflecting the needs and desires of
      senior citizens and professional requirements regarding accessible housing as a
      means to inform and influence housing provision policies. 

PMID- 26294489
TI  - How to live independently with or without technology?
AB  - This qualitative study aims to identify how Finnish elderly, aged 65-82, consider
      technology as part of their life and how the learning of using technology is
      happening. Thematic interviews were carried out and transcribed to text. Content
      analysis was done and common elements were found. The analysis was done in
      researcher triangulation to enhance the reliability of the data extraction. Two
      main categories were named: lived life and the role of ICT/ICT AT, ICT support
      and education. We can conclude that the results showed that there is a need to
      integrate ICT/ICT AT education into the daily life and rehabilitation of elderly.
      The most common need to use ICT is to be connected and to be able to follow the
      society. Also open discussion is needed concerning the divide between older and
      younger citizens. Based on the results the non-users who don't want to use
      technology also need to be considered in society by developing new service
      solutions for all. If being positive towards using technology this study showed
      that ICT skills can positively affect feeling of self-determination and quality
      of life. 

PMID- 26294490
TI  - Platform for frail elderly people supporting information and communication.
AB  - There is a growing need for technology to support the frail elderly living
      independently in home situations. Several telecommunication systems already
      exist. These systems are developed mainly from the perspective of healthcare
      professionals and focus on efficient delivery of healthcare services. They hardly
      meet the specific needs of the frail elderly. In this project a platform with
      specific needs of the frail elderly people has been designed, running on standard
      PCs. This system supports living independently, social participation, wellbeing,
      and asking for care services. The platform was evaluated and subjects assess the
      system as user friendly, and supportive for their independence and self-reliance.
      They recommend it to other users. 

PMID- 26294491
TI  - Distributed cognition, dementia, and technology.
AB  - The devastating effects of dementia result from cognitive degradation, in
      particular, working-memory (short-term memory) and planning processes. In
      supporting people with dementia, carers must take over these cognitive functions
      on behalf of the other person. This is an exhausting job. Technology may be able
      to offer assistance here. Its development will be encouraged by viewing cognition
      as a distributed process, and not just as something that happens inside one
      person's head. This paper argues for this approach, with examples from existing
      technical and non-technical systems of support for people with dementia which
      have been proven to work. 

PMID- 26294492
TI  - Mapping City Accessibility: Review and Analysis.
AB  - The paper presents an analysis of prototypes, studies, and applications for the
      mapping of city accessibility, focusing mainly on sidewalks accessibility.
      Moreover, it presents the results of two focus groups that we organized both with
      electric and with manual wheelchairs to attain requirements and insights to
      design a user-friendly app for the collection and visualization of information
      about the accessibility of urban pedestrian pathways. 

PMID- 26294493
TI  - SIMON: Integration of mobility and parking solutions for people with
      disabilities.
AB  - Mobility and parking in urban areas are often difficult for people with
      disabilities. Obstacles include lack of accessible information on routes,
      transport alternatives and parking availability, as well as fraud in the use of
      the specific services intended for these citizens. The SIMON project aims to
      improve this situation through the integration of different ICT solutions. SIMON
      is enhancing the European Parking Card for disable people with contactless
      technologies and integrates mobile solutions to support user unique
      identification in existing parking areas whilst preserving privacy. SIMON will
      also promote better mobility solutions for mobility including information,
      navigation and access to restricted areas. 

PMID- 26294495
TI  - ODINS: On-Demand Indoor Navigation System RFID Based.
AB  - This paper presents an On-Demand Indoor Navigation System (ODINS) based on RFID
      technology. ODINS is a distributed infrastructure where a set of information
      points (Fixed Stations - FS) provides the direction to a user who has to reach
      the destination point he/she has previously selected. ODINS system is proposed
      for residencies hosting people with mild cognitive disabilities and elderly but
      it can be also applied to structures where people could be disoriented. The
      destination is configured at some reception points or it is a predefined (e.g.
      the bed room or a selected "safe" point). The destination is associated with a
      RFID disposable bracelet assigned to her/him. The path is algorithmically
      computed and spread to all FSs. Every time the user is disoriented, she/he can
      search for the closest FS that displays the right directition. FSs should be
      located in strategic positions and provide a user-friendly interface such as
      bright arrows. The complexity is "system-side" making ODINS usable for everyone. 

PMID- 26294494
TI  - Examples of the application of the cause-effect ergonomic evaluation model to the
      wheelchair cushions.
AB  - This article highlights the potential of the application of the cause-effect
      model for the ergonomic evaluation in the field of cushions. User involvement in
      the prescription and development of assistive devices have been identified a key
      aspect for positive interventions, although the reality is that we lack of
      systematic approaches and examples of best practices. The potential benefits are
      identified for the development of new products and in the prescription process.
      Additional research would be necessary to better link the characteristics of the
      cushions and users with the biomechanical and physiological performance of the
      interface cushion-user and the consequences measured in health, user perception
      and activity performance. This article shows examples of the relationship in this
      three levels from the point of view of the user perception. 

PMID- 26294496
TI  - Barriers and Facilitators to Uptake of Assistive Technologies: Summary of a
      Literature Exploration.
AB  - This paper aims to highlight some of the issues that arise with the uptake of
      assistive technology as found in the literature across four different domains:
      Telehealth; Telecare; Augmentative and Alternative Communication; and Education.
      The authors were not looking so much at service delivery models as user centred
      experiences and key words that were used to describe outcomes. The results showed
      remarkable similarities in the concerns of patients, families, users and other
      stakeholders. However, different terminologies across the fields highlighted the
      gulf between the fields, with professional 'silo-ing' of expertise occurring.
      There is a necessity for increased collaboration that could allow for knowledge
      sharing and enhanced assessment, uptake and continued use of assistive
      technologies for all potential users. 

PMID- 26294497
TI  - The Assistance Dog System in Finland. An Overview of the Current Situation and
      Suggestions.
AB  - This paper describes the current situation of the assistance dog system in
      Finland; problems, development needs, benefits of assistance dogs and suggestions
      for a new system. 

PMID- 26294498
TI  - Progress of the European Assistive Technology Information Network.
AB  - The European Assistive Technology Information Network (EASTIN), launched in 2005
      as the result of a collaborative EU project, provides information on Assistive
      Technology products and related material through the website www.eastin.eu. In
      the past few years several advancements have been implemented on the EASTIN
      website thanks to the contribution of EU funded projects, including a
      multilingual query processing component for supporting non expert users, a user
      rating and comment facility, and a detailed taxonomy for the description of ICT
      based assistive products. Recently, within the framework of the EU funded project
      Cloud4All, the EASTIN information system has also been federated with the Unified
      Listing of assistive products, one of the building blocks of the Global Public
      Inclusive Infrastructure initiative. 

PMID- 26294499
TI  - Collaboration between Industrial Designers and Design Engineers - Comparing the
      Understanding of Design Intent.
AB  - This paper describes a case study comparing the understanding of design intent
      between industrial designers and design engineers. The study is based on the
      hypothesis that it is not all aspects of the design intent that are equally
      difficult to share between industrial designers and design engineers in the
      product development process. The study builds on five semi-structured interviews,
      where two industrial designers and three design engineers were interviewed about
      different aspects of the design intent. Based on our results, there seem to be
      indications that the more complex and abstract elements of industrial design
      knowledge such as the meaning, semantics, values, emotions and social aspects of
      the product are less shared by the design engineers. Moreover, the results also
      indicate that the different aspects of the design intent are perceived
      separately, rather than as part of a whole by the design engineers. The
      connection between the different aspects of the design intent is not shared
      between the industrial designer and design engineer making the shared knowledge
      less meaningful to the design engineers. The results of this study cannot be
      claimed to be conclusive due to the limited empirical material. Further
      investigation and analytically richer data are required in order to verify and
      broaden the findings. More case studies have therefore been planned in order to
      understand the area better. 

PMID- 26294500
TI  - Balancing game universes for playing without sight or hearing.
AB  - Equal access to cultural activities is important for inclusion and computer
      gaming is one of the most common activities in digital culture. However, many
      people with impairments are excluded from participating. While parallel game
      universes (PGUs) provide a method to achieve equal access, the question is: how
      can a balanced collaborative real-time game be designed with the help of PGU for
      playing without sight or hearing? Balance is a central concept in game design and
      is important to avoid perceived cheating or disadvantages due to individual or
      environmental differences. The question was examined with a design science
      approach, where a game prototype was created in two iterations with a structured
      design method and evaluated using interviews and observations. In this first step
      of a more long-term study, ten experienced gamers without impairments were
      selected with purposive sampling to provide relevant data through simulation of
      temporary impairments or environmental issues, which can affect many or all
      gamers. By sorting out these issues first, later testing with actual blind and
      deaf gamers can focus on more specific issues for each group. The ten
      participants played either without sight or hearing. The results confirm the use
      of PGUs for creating a balanced experience but also finds that while multiplayer
      feel is not optimal, it is a reasonable trade-off for universal access for blind
      and deaf being able to play together. The results also show that a help system
      and equal understanding of the game play between the blind and deaf players are
      important aspects to achieve game balance. Further research should be done
      involving actual blind and deaf gamers, and similar evaluations of game balance
      should be conducted with users having other types of impairments. 

PMID- 26294501
TI  - Embedded systems for supporting computer accessibility.
AB  - Nowadays, customized AT software solutions allow their users to interact with
      various kinds of computer systems. Such tools are generally available on personal
      devices (e.g., smartphones, laptops and so on) commonly used by a person with a
      disability. In this paper, we investigate a way of using the aforementioned AT
      equipments in order to access many different devices without assistive
      preferences. The solution takes advantage of open source hardware and its core
      component consists of an affordable Linux embedded system: it grabs data coming
      from the assistive software, which runs on the user's personal device, then,
      after processing, it generates native keyboard and mouse HID commands for the
      target computing device controlled by the end user. This process supports any
      operating system available on the target machine and it requires no specialized
      software installation; therefore the user with a disability can rely on a single
      assistive tool to control a wide range of computing platforms, including
      conventional computers and many kinds of mobile devices, which receive input
      commands through the USB HID protocol. 

PMID- 26294502
TI  - Emergent Application on Smart Phone for Deaf, Language Dysfunction and
      Foreigners: -  Communication method to perform swift rescue report by refined
      icons with GPS technology.
AB  - This paper discusses the efficiency of the Emergent Application on Smart Phones
      (EASP). In an initial survey, hearing impaired people are asked to explain their
      difficulties in an emergency situation. With this survey as background, an
      application with five steps is implemented on Smart Phone touch panels using
      outcome icons and pictograms to communicate to a call centre in the fire brigade.
      The evaluation results with EASP application by deaf people found that it was
      about five times quicker to report an emergency using this tool, than it by using
      text message input. 

PMID- 26294503
TI  - Versatile Text Extraction System for Text-to-Speech Reading Assistant Camera.
AB  - Wearable camera device translating the text in the scene into speech is one of
      the most anticipated devices for the visually-impaired. The users would probably
      want to read any text using such a device. Although various scene text extraction
      methods have been developed so far, the target objects are most often limited to
      simple signboards, small memos, etc. We propose a versatile scene text extraction
      method that can handle a wide variety of targets including complex signboards
      with many text lines. Experimental results show that our system runs at a video
      rate and can extract densely arranged text lines even with some distortion and
      shading. A locally-adaptive binarization technique contributes to the better
      quality of extracted text images. 

PMID- 26294505
TI  - Visual functioning of aging care professionals and the influence of light, a
      brief literature study.
AB  - Ageing is an important factor that affects visual functioning. In the Netherlands
      the average age in healthcare facilities is on increase. The current study is a
      preliminary literature review regarding the influence of light on the visual
      functioning of the aging workforce and their related tasks. 

PMID- 26294504
TI  - Validation of Mobility of Pedestrians with Low Vision Using Graphic Floor Signs
      and Voice Guides.
AB  - Some people with low vision or elderly persons tend to walk while watching a
      nearby floor, therefore, they often overlook or hard to read suspended signs. In
      this study, we propose two kinds of voice guides, and an experiment is conducted
      by participants with low vision using these voice guides and graphic floor signs
      in order to investigate effectiveness of these combinations. In clock position
      method (CP), each direction of near facilities are described in using an analogy
      of a 12-hour clock. Meanwhile, in numbering method (NU), near facilities are put
      the number in clockwise order, however, each direction are only illustrated in a
      crossing sign. As a result of an experiment, it is showed that both voice guides
      are effective for pedestrians with low vision. NU is used as a complement of
      graphic floor signs. Meanwhile, CP is used independently with graphic floor
      signs, however, there is a risk in the case of using in the environment where
      pedestrians are easy to mistake the reference direction defined by the sounding
      speaker. 

PMID- 26294506
TI  - Creating healthy nursing home environment via lighting interventions: a
      theoretical approach.
AB  - In the Netherlands long-term care facilities made investments in order to improve
      the well-being of their residents and to support healthcare professionals in
      their daily task. Light is one of the technical solutions that might be
      contribute to support the well-being of older residents in long-term care
      facilities. This study investigates which possibilities are available to enrich
      the current situation to support the well-being, activities of daily living, and
      quality of life of older residents from lighting perspective. The light
      measurements show that the conditions are low and the value of 750 lux mainly
      reached on measurements points close to the window area. In this field study the
      light conditions are improved through a static lighting system. Further research
      is needed in order to investigate how the new light plan affect the quality of
      life and to define light guidelines for long-term care facilities. 

PMID- 26294507
TI  - Measurements of speech intelligibility in common rooms for older adults as a
      first step towards acoustical guidelines.
AB  - Adapting the built environment to the needs of nursing- or care-home residents
      has become common practice. Even though hearing loss due to ageing is a normal
      occurring biological process, little research has been performed on the effects
      of room acoustic parameters on the speech intelligibility for older adults. This
      article presents the results of room acoustic measurements in common rooms for
      older adults and the effect on speech intelligibility. Perceived speech
      intelligibility amongst the users of the rooms was also investigated. The results
      have led to ongoing research at Utrecht University of Applied Sciences and
      Eindhoven University of Technology, aimed at the development of acoustical
      guidelines for elderly care facilities. 

PMID- 26294508
TI  - Development of the Environmental Observation scale for the Visual Impaired.
AB  - In order to raise awareness of professional care, an Environmental Observation
      scale for the Visual Impaired (EOVI) was developed. It is the purpose of this
      tool that professional caregivers learn to observe the nursing home environment
      and consequently propose and discuss potential changes in the short and long
      term. The mean time of filling out the EOVI in eight wards of a nursing home by
      two student researchers was 17 minutes (min mean 12, max mean 22,5). All of 10
      optometry students reported that the EOVI changed their awareness. 

PMID- 26294509
TI  - The influence of dry eye and office environment on visual functioning.
AB  - Environmental factors, such as high airflow and low relative humidity, are known
      to promote dry eye symptoms during reading tasks in office workers. These
      symptoms are associated with an adverse impact on daily activities at work. This
      study reports on the relationship between eye symptoms and environmental factors
      in 294 employees at one office location. 

PMID- 26294510
TI  - Using a Pressure Mapping System to Evaluate Contact Pressure on Hands During Use
      of Axillary Crutches.
AB  - The aim of this study was to evaluate different handles used in axillary crutches
      with a Pressure Mapping System. The Grip Versatek system from Tekscan Inc. was
      used to measure the levels and the distribution of contact pressure in the hands
      during a simulated activity of ambulation with crutches. The sample included ten
      able-bodied subjects: five men and five women. The results show that the
      different models of handles appear to have influenced the pressure levels
      measured during the activity. Therefore, the measurement equipment provides
      parameters that allow the comparison among different designs and assess their
      contribution to the comprehension of the demands of ergonomic handles. 

PMID- 26294511
TI  - PONS - Mobility Assistance on Footpaths for Public Transportation.
AB  - This paper presents an ongoing project targeting mobility support for users of
      public transportation including people with limited mobility. Existing approaches
      in this field mostly offer non-continuous guidance during the whole journey
      including multiple rides with different vehicles and footpaths in between at
      transfer points. Especially people with limited mobility, like people with
      disabilities and elderly people, or travelers who are not familiar with the
      specific route or transfer point, like tourists, often struggle with public
      transportation. They crave for a seamless approach covering all links of the
      mobility chain - the sequence of sections of the whole route - and providing
      comprehensive assistance throughout the whole journey. Previous projects and
      widespread experiences of project partners revealed that especially footpath
      sections are lacking proper support. In particular, the consortium identified
      three problem areas in existing approaches when dealing with footpath sections:
      (1) A lack of information, (2) a lack of orientation and (3) a lack of provision
      of services. In order to bridge (lat. PONS) these gaps in the mobility chain, new
      paradigms and technology concepts are developed to tackle the shortcomings on
      footpaths and combined in a toolkit to help developers of applications with focus
      on pedestrian navigation and public transport to improve their solutions with
      sustainable and state-of-the-art approaches. 

PMID- 26294512
TI  - Biomechanics and Physiology for Propelling Wheelchair Uphill Slope.
AB  - A vertical slope of sidewalks significantly inhibits to the mobility of manual
      wheelchair users in their daily life. International guidelines of the vertical
      slope are specified approximately 4% or 5% (1:20) gradient or less as preferred,
      and allow 8.3% (1:12) as its maximum when it is impossible. Relevant research of
      the physical strain for wheelchair users with pushing on slopes, and the validity
      assessment of slope guidelines have been investigated. However, the analysis for
      the effect of a slope distance and their transient performance are still
      remained. The purpose of this study is to clarify the physiological and
      biomechanical characteristics of manual wheelchair users that propelling a
      wheelchair on an uphill slope. We measured these data by a metabolic analysis
      system, a heart rate monitor system and an instrumented wheelchair wheel. Sixteen
      unimpaired subjects (non-wheelchair users) were examined to investigate the
      effect of a long slope with 120m distance and 8% gradient. And five wheelchair
      users with cervical cord injury were examined to evaluate the influence of
      different gradients (5%, 6.7%, 8.3%, 10% and 12.5%) with 3m length in laboratory.
      Our experimental results of the long slope showed that wheelchair propulsion
      velocity and power increased considerably at the beginning of the slope where the
      peak mean value of them were 0.96 m/s and 70.8W and they decreased linearly to
      0.55m/s and 33.6W at final interval. A mean oxygen uptake and heart rate were
      increased as the distance increased and their results indicated the extremely
      high exercise intensity at a final interval that were 1.2liter /min and 152bpm.
      While wheelchair pushing cadence reduced after an initial interval, mean of
      strokes per10m increased to compensate the decrease of upper limb's power. The
      results of different gradients indicated that the normalized power of subjects
      with cervical cord injury was significant difference between each subject in the
      ability to climb a slope. Mean normalized power were 0.23W/kg on a 5% slope,
      0.24W/kg on 6.7%, and 0.26W/kg on 8.3% respectively. Based on these findings, we
      examined the relationship between the theoretical normalized power and the lowest
      velocity to climb a slope, and we might indicate the ability to push on an uphill
      slope for the persons with manual wheelchair user. 

PMID- 26294513
TI  - Agile Walker.
AB  - The goal of the Agile Walker is to improve the outdoor mobility of healthy
      elderly people with some mobility limitations. It is a newly developed, all
      terrain walker, equipped with an electric drive system and speed control that can
      assists elderly people to walk outdoors or to hike. The walker has a unique
      product design with an attractive look that will appeal to "active-agers"
      population. This paper describes product design requirements and the development
      process of the Agile Walker, its features and some preliminary testing results. 

PMID- 26294514
TI  - Way-Finding Support in Public Transport Environments provided by the NAMO Mobile
      Travel Assistance System.
AB  - The NAMO travel assistance system is a mobile application providing support for
      elder travellers in public transport and on foot. The system combines technical
      and human support during the journey, especially in situations where many seniors
      experience orientation difficulties. Several approaches to way-finding and
      orientation support have been developed. This paper introduces the different
      approaches and presents the results of the extensive user evaluations, leading to
      recommendations for future development of mobile travel assistance applications
      for seniors. 

PMID- 26294515
TI  - How to Accomplish the Assistive Technology Service Delivery Process for Adults in
      Order to Obtain the Best Outcomes - A Literature Review.
AB  - In order to gain knowledge about which methods in the assistive technology
      service delivery process or parts hereof that result in positive outcomes, a
      literature review was accomplished. 20 publications were included. Some evidence
      was found that user involvement in the service delivery process and training in
      assistive device use had a positive impact on outcomes. Also professionals'
      higher assistive device expertise seems to result in better outcomes. More
      research within the field is needed, especially studies that compare the
      effectiveness and cost-effectiveness of specific methods applying controlled
      study designs. 

PMID- 26294516
TI  - Assessing Service Delivery Systems for Assitive Technology in Brazil using HEART
      Study quality indicators.
AB  - BACKGROUND: recently in Brazil, there have been investments and improvements in
      the service delivery system for assistive technology provision. However, there is
      little documentation of this process, or evidence that users are being involved
      appropriately. OBJECTIVE: to understand how a ssistive technology service
      provision currently functions in Belo Horizonte city, Brazil, in order to provide
      context-specific interventions and recommendations to improve services. METHOD:
      Qualitative research design, including visits to key institutions and semi
      structured interviews with key stakeholders. Interview questions were divided
      with two purposes: 1) Exploratory, aiming to understand present service
      functioning; 2) Evaluative, aiming to assess staff difficulties in applying best
      existing best practices. RESULTS: Assistive Technology services in Belo Horizonte
      fall under the 'medical model' definition of service delivery developed by AAATE.
      It was also found that staff lack training and knowledge support to assess user
      requirements and involve them during the decision process. Additionally, there is
      no follow up stage after the device is delivered. CONCLUSIONS: The study clearly
      defines the service provision function and the staff difficulties at Belo
      Horizonte city, providing information for further studies.

PMID- 26294517
TI  - The relationship between the key elements of Donabedian's conceptual model within
      the field of assistive technology.
AB  - Previous research has suggested that there is a relationship between the three
      key components of Donabedian's conceptual model for quality assessments:
      structure of care, process, and outcome of care. That is, structure predicted
      both process and outcome of care, and better processes predict better functional
      outcomes and user satisfaction. The results in this study involving samples of
      Danish and Norwegian scooter users indicate that structure predicts what goes on
      in the service delivery process. However, the results do not support that
      structural differences or differences in the service delivery process predict the
      outcomes of the scooter interventions. 

PMID- 26294518
TI  - Implementing UNCRPD - Barrier Free Access to Buildings in NRW - Database and
      Signet "NRW Inklusiv".
AB  - UNCRD [1] has reemphasized the relevance of barrier free accessibility to
      infrastructures. Article 9 deals with accessibility of the manmade environment
      including buildings. Although accessibility has been required by people with
      disabilities for decades the existing built infrastructure often lacks adequate
      accessibility. If at all, it addresses requirements for users of wheelchairs but
      not for users with sensory or cognitive challenges. In this paper the development
      of a survey and publication of data from buildings is reported. The methodology
      is based on user participation and inclusion and follows a civil society
      approach, embedded in the overall strategy for inclusion in North Rhine
      Westphalia (Germany). The internet portal presenting the information to the
      public is a first step to improve accessibility. An award on this data basis is
      proposed as incentive. 

PMID- 26294519
TI  - Developing Deep Water Excercise Equipment for Low Back Pain (LBP) Patients:
      medical validation experiences.
AB  - Authors describe a joint work of practicing physicians and rehabilitation
      specialist engineers. In our work we wanted to prove the efficacy of deep-water
      physiotherapy among the hydrotherapy treatments in patients with degenerative
      chronic low back pain, by monitoring both objective and subjective parameters. On
      the other hand, we are also seeking the possibilities of developing a water
      exercise tool which can spare the shoulders, can be used in deep water and is
      suitable for helping the three-dimensional movements of the spine without
      burdening the upper limbs and shoulders. 

PMID- 26294520
TI  - Proposal for SVG2DOT: -  An Interoperable Tactile Graphics Creation System Using
      SVG outputs from Inkscape.
AB  - For this study, I developed a software that converts SVG outputs from Inkscape to
      tactile graphics. Inkscape is easy to learn because it can be manipulated like
      any other typical drawing application and has a layer function which is enables
      robust support in the creation of tactile graphics In a simple evaluation, it is
      confirmed that the method of drawing a master in Inkscape and converting it with
      SVG2DOT was nearly as efficient as using a conventional tactile graphics drawing
      application. 

PMID- 26294521
TI  - Visibility of LED Blocks Mounted on Crosswalk Boundaries for low Visual Capacity.
AB  - According to the WHO, about 80% of visually impaired persons in the world are
      with low visual capacity. It is considered that LVs' safe independent mobility
      will be improved as employing Tactile Walking Surface Indicators (TWSIs). In the
      night, guidelines for constructing warning blocks, a kind of tactile surface
      indicator, have not been well established. Therefore, crossing crosswalks is one
      of the most dangerous situations for visually impaired persons. We thus developed
      novel LED blocks that indicate crosswalk boundaries between sidewalks and
      roadways. This study addresses the LED blocks under various environmental
      illuminations and illumination from the opposite side of the crossing. 

PMID- 26294522
TI  - Development of a Portable Two-Way Communication and Information Device for
      Deafblind People.
AB  - This paper presents research on the development of a wearable two-way
      communication and information device for deafblind people who use tactile
      communications methods, namely the British deafblind manual alphabet and/or
      Braille. The device has two components: a glove worn by the deafblind person and
      a handheld display with keypad to be used by their hearing and sighted
      communication partner. Users can send messages using pressure sensors embedded in
      the glove and receive them by means of vibration on the palm. The two components
      are linked by Bluetooth and the use of Bluetooth to communicate with computers,
      mobile phones and other Bluetooth enabled devices is being investigated. The
      design was informed by feedback obtained from a survey of deafblind people and
      interviews with staff in two organisations for deafblind people. Research and
      development of the device is still ongoing. 

PMID- 26294523
TI  - Wearable technology to help with visual challenges - two case studies.
AB  - Today as embedded computing technology and sensors become cheaper and smaller
      wearable technologies experience an unprecedented boom. This article presents two
      wearable systems that aim to help people with low vision and the blind in
      performing everyday tasks and doing sports. DIGIGLASSES is a project aimed at
      creating a pair of augmented reality digital glasses that present controlled
      light and contrast levels and marks selectable features on the field of vision to
      aid in everyday tasks. BLINDTRACK is guidance system that uses wireless
      localization and an innovative haptic feedback belt to guide blind runners along
      the running track. Both systems are briefly presented along with the most
      relevant technical details and user feedback where applicable. Both projects were
      funded by the EU FP7. Corresponding author V. Kalman: viktor.kalman@ateknea.com. 

PMID- 26294524
TI  - 2D Presentation Techniques of Mind-maps for Blind Meeting Participants.
AB  - Mind-maps, used as ideation technique in co-located meetings (e.g. in
      brainstorming sessions), which meet with increased importance in business and
      education, show considerably accessibility challenges for blind meeting
      participants. Besides an overview of general aspects of accessibility issues in
      co-located meetings, this paper focuses on the design and development of
      alternative non-visual presentation techniques for mind-maps. The different
      aspects of serialized presentation techniques (e.g. treeview) for Braille and
      audio rendering and two dimensional presentation techniques (e.g. tactile two
      dimensional array matrix and edge-projection method [1]) are discussed based on
      the user feedback gathered in intermediate tests following a user centered design
      approach. 

PMID- 26294525
TI  - Operational Assistance for Elderly People by Using Audio Rhythms.
AB  - Recently, Information Technology (IT) machines with complicated function are
      requiring better user assistance, particularly for elderly people. It is
      necessary to reduce the psychological load such as a sense of insecurity and
      impatience in operation, as well as the cognitive load. One approach to reduce
      psychological load is voice guidance. However many elderly people may become
      confused due to the speed of guidance. Sometimes it is too fast or too slow.
      Ideally it must synchronize to the user's operational pace reflecting context of
      use. This research focuses on enhanced operational rhythm to reduce psychological
      load on the elderly when using a Multiple Function Printer (MFP), which requires
      the user to navigate between quite a few settings. Evaluation was carried out by
      observing elderly subjects using an MFP interface whilst hearing a metronome at a
      tempo of 40, 60 and 120 bpm (beats per minute). The number of operational errors
      and overall time taken were recorded along with subjective evaluation via
      interviews with the subjects. The results showed that providing audio rhythm is
      effective, however a rhythm which is too fast produces a negative effect. 

PMID- 26294526
TI  - Beyond qualitative and subjective techniques to assess usability of banking
      interfaces for senior citizens.
AB  - Senior citizens can benefit from banking services but the lack of usability
      hampers this possibility. New approaches based on physiological response, eye
      tracking and user movement analysis can provide more information during interface
      interaction. This research shows the differences depending on user knowledge and
      use of technology, gender and type of interface. 

PMID- 26294527
TI  - Automatic Quiz Generation for the Elderly.
AB  - According to the literature, ageing causes declines in sensory, perceptual, motor
      and cognitive abilities. The combination of reduced vision, hearing, memory and
      mobility contributes to isolation and depression. We argue that memory games have
      potential for enhancing the cognitive ability of the elderly and improving their
      life quality. In our earlier research, we designed tangible tabletop games to
      help the elderly remember and talk about the past. In this paper, we report on
      our further research in the automatic generation of quizzes based on Wikipedia
      and other online resources for entertainment and memory training of the elderly. 

PMID- 26294528
TI  - SHARON: a Simulator of Human Activities, ROutines and Needs.
AB  - In a few decades, requests for assistance to the elderly will increase the
      already high health care costs. Within this context, a possible solution is
      represented by smart environments where services help dwellers' life. The
      development of smart technologies requires large datasets for training,
      validation or testing. Since the data collection from real smart homes has high
      costs the authors developed SHARON - a Simulator of Human Activity, ROutines and
      Needs. This software aims to support such projects, virtually reproducing
      environments and behaviors of the dwellers. This work proposes and validates a
      behavioral model able reproduce decisions and human habits, starting from an
      available data set or an interview. Physiological parameters and habits are
      merged with a probabilistic approach, choosing the most likely activity. With
      respect to other behavioral simulators available in the literature, SHARON is
      focused on routines and activities generation, based on user defined high level
      parameters. Within the evaluation phase it was applied a cross-validation
      approach, by simulating 300 days starting from a training set of 23 days and
      testing with the remaining 7 days validation set. As expected, results prove the
      simulated data correctly reproduce the activities routine distributions, in
      particular the more regular ones. 

PMID- 26294529
TI  - Deciding to apply for, receiving and starting to use assistive technology devices
      - an enigmatic journey: -  A qualitative study of the experiences of older
      individuals.

PMID- 26294531
TI  - 4D-Joystick - New Possibilities for Persons with Motor Disabilities.
AB  - The 4D-Joystick is a new type of Assistive Technology which enables people with
      severe motor disabilities to fully control remote controlled (RC) toys i.e.
      MODELS: In 2013 the authors started to develop a feasibility study and built the
      first prototype of the 4D-Joystick which allowed to control up to 4 analogue and
      up to 2 digital channels. The second prototype of the 4D-Joystick allows to
      control up 4 analogue channels and 4 digital channels concurrently with very low
      latency. Furthermore the second prototype of 4D-Joystick supports functionality
      like Dual Rates, Expo, Invert and Dead Zone on each channel which offers
      additional adaptability to the users' needs. This is sufficient to control
      complex RC Models like airplanes, helicopters, multicopters, boats and cars.
      Furthermore the 4D-Joystick offers an interface to the open source software
      AsTeRICS. In combination with AsTeRICS the 4D-Joystick can be used as music
      instrument, a computer game controller and a computer input device. This paper
      discusses the second prototype of the 4D-Joystick and its functionality.

PMID- 26294530
TI  - ICT based technology to support play for children with severe physical
      disabilities.
AB  - INTRODUCTION: Play is important for a child's development. Children with severe
      physical disabilities experience difficulties engaging in play. With the progress
      of technology the possibilities to support play are increasing. The purpose of
      this review was to gain insight into the possibilities and availability of ICT
      based technology to support play in children with severe physical disabilities.
      METHODS: A systematic literature search within the databases PubMed, CINAHL, IEEE
      and ERIC was carried out. Three reviewers assessed titles and abstracts
      independently. Additionally, Google Scholar, conference proceedings and reference
      lists were used. RESULTS AND CONCLUSION: The included publications reported on 27
      different technologies, which can be classified into three main groups; robots,
      virtual reality systems and computer systems. There are several options that may
      have great potential in supporting play for this target group.

PMID- 26294532
TI  - Sweet Cheese. Back to the Physical World.
AB  - Sweet Cheese (switches) is a physical device that brings back the virtual
      keyboards to the physical world. Although the virtual keyboards are useful for
      people with motor impairment, they require to be used in a windowed environment.
      This is sometimes impossible due to the imposed full screen mode. We present in
      this paper our solution that mixes advantages of both physical and virtual
      keyboards. 

PMID- 26294533
TI  - Human-computer interface using a head mounted camera and IR markers.
AB  - This paper describes an alternative way to control the selection of items in
      computing devices. A survey of the issues of the current state-of-the art is
      performed and a solution is presented based on a cheap, head-mounted, IR
      sensitive camera tracking IR LEDs. Benefits related to this approach are
      indicated, initial performance results are presented from which we can conclude
      the feasibility of the proposed solution. 

PMID- 26294534
TI  - Supporting shoulder rehabilitation - designing simple devices aiding
      physiotherapy.
AB  - The authors present simple devices which can facilitate and improve shoulder
      rehabilitation following various conditions. These commercially available and
      easily assembled functional aids improve patient experience and allow the bulk of
      the rehabilitation to take place in the patients' home environment. 

PMID- 26294535
TI  - How assistive technology changes the brain: the critical role of hippocampal
      striatal interactions during cognitive training.
AB  - Recent studies found structural changes of the brain during cognitive training.
      These changes may be important when assistive technologies are used, for example,
      to boost memory and navigation abilities in patients with neurocognitive
      disorders. In this study, we show that extensive training with a platformer game
      simulating navigation and real-life spatial abilities, patients with Alzheimer's
      disease and amnestic mild cognitive impairmant exhibit an increased volume of the
      caudate nucleus in contrast to healthy individuals who display increased
      hippocampal volumes. These results raise the possibility that cognitive training
      and assistive technology may induce compensatory changes of brain structure in
      memory disorders. 

PMID- 26294536
TI  - Can Disability Code Activation Promote Sustainable Development in Egypt... After
      the Arab Spring?
AB  - In January 2011, Egypt followed Tunisia in its Uprisal against the ruling
      oppressive regimes in search for democracy, freedom and better living conditions.
      The movement, later known as the Arab Spring, had implications on the country's
      economic and political systems. Hence, the need to adopt Sustainable Development
      strategies and that in order to ensure all people well being, and the
      implementation of their human rights. This would only be realized when the built
      environment would become accessible to vulnerable people, as well as to persons
      with disabilities and would enable them to participate and be included in various
      living activities. This paper reviews the impact of the Egyptian disability code,
      that was published 2003, and how its activation could help to provide the
      environment that supports persons with disabilities, and allows their
      integration. Key Words: Disability Code; Sustainable Development; Arab Spring;
      Accessible Enabling Environment, People with Disabilities Integration. 

PMID- 26294537
TI  - The role of emotional intelligence in vocational rehabilitation with special
      respect to physically and cognitively disabled persons.
AB  - In the past several years we have done a research about the processes and the
      actors of workforce rehabilitation in Hungary. We have discovered some strengths
      and flaws of that processes, and based on that research we would like to see a
      turning point in the near future. We think that one of the keys of the success in
      the processes of the rehabilitation of workforce is the attitude of the positive
      psychology. Based on our researches the emotional competences and psychological
      immunity have been found to have very important and special roles in the personal
      side of the rehabilitation process. The attitude of the employers and the society
      to the rehabilitation is also important based also on the emotional awareness. 

PMID- 26294538
TI  - Service composition towards increasing end-user accessibility.
AB  - This paper presents the Cloud4all Service Synthesizer Tool, a framework that
      enables efficient orchestration of accessibility services, as well as their
      combination into complex forms, providing more advanced functionalities towards
      increasing the accessibility of end-users with various types of functional
      limitations. The supported services are described formally within an ontology,
      enabling, thus, semantic service composition. The proposed service composition
      approach is based on semantic matching between services specifications on the one
      hand and user needs/preferences and current context of use on the other hand. The
      use of automatic composition of accessibility services can significantly enhance
      end-users' accessibility, especially in cases where assistive solutions are not
      available in their device. 

PMID- 26294540
TI  - Walking Characteristics of Persons with Visually Impairment Crossing
      Intersections with Audible Pedestrian Signals.
AB  - The authors have been continuously researching tactile walking surface indicators
      and audible pedestrian signals used for crossing intersections. A pedestrian
      walks to the opposite side of the crosswalk using audible pedestrian signals. The
      position where the audible pedestrian signal is set up clearly influences the
      pedestrian's path. We performed an intersection crossing experiment with road
      noise for different positions where the audible pedestrian signal was set up.
      Vehicle road noise is thought to influence walking pedestrians. However, we could
      not clearly separate the difference of where the audible pedestrian signal was
      set up from the influence of the road noise. We therefore conducted the
      experiment with no road noise in the intersection to determine the difference of
      the position where the audible pedestrian signal was set up. The research results
      were compared with and without road noise to specify the road noise influence. 

PMID- 26294539
TI  - A qualitative study to evaluate strategies for changes in the assistive
      technology service delivery in Flanders.

PMID- 26294541
TI  - Intuitive tactile algorithms to guide blind runners by means of a belt with
      vibrators.
AB  - Visually impaired people do not have equal possibilities to practice sports. In
      the case of running they need a sighted guide. This paper compare different
      possibilities for indicating direction to blind people by means of a belt that
      transmits tactile messages, and defines design requirements based on
      anthropometric analysis. The results shows that intuitive tactile messages are
      achieved with tactile stimuli applied in the ventral section, from the iliac
      crests to the navel. 

PMID- 26294543
TI  - Locating assistive technology research in a clinical setting: an occupational
      perspective.
AB  - Peer research was used to identify the experience and perceptions of assistive
      technology and telecare adoption in a UK healthcare context. A narrative account
      of participation and learning is intended to provoke further dialogue. There have
      been a range of policy and implementation initiatives that are within the direct
      experience of organisational actors over the last 15 years and this engagement
      allows for specific reflection on the service achievements and some of the
      barriers to implementation of technology changes in rehabilitation practice and
      service design. Insights are presented that suggest a reification of research
      priorities and a need to align technology, through patient and public engagement,
      to provider priorities. In addition, an improvement in adoption would be based on
      sustained capacity building within the Occupational Therapy workforce and a re
      focus on specific knowledge sharing and learning about technology. Given the
      shared desire to promote the sustained adoption of appropriate technology for
      assistance and rehabilitation it is suggested the voice of practitioners is
      strengthened through research and knowledge exchange in the clinical setting. 

PMID- 26294542
TI  - Validation of the ULCEAT methodology by applying it in retrospect to the
      Roboticbed.
AB  - BACKGROUND: In answer to the increasing demand for care by the Japanese oldest
      portion of the population, an extensive programme of life support robots is under
      development, advocated by the Japanese government. Roboticbed<sup>(r)</sup> (RB)
      is developed to facilitate patients in their daily life in making independent
      transfers from and to the bed. The bed is intended both for elderly and persons
      with a disability. OBJECTIVE: The purpose of this study is to examine the
      validity of the user and user's life centred clinical evaluation of assistive
      technology (ULCEAT) methodology. To support user centred development of life
      support robots the ULCEAT method was developed. By means of the ULCEAT method the
      target users and the use environment were re-established in an earlier study.
      METHOD: The validity of the method is tested by re-evaluating the development of
      RB in retrospect. Six participants used the first prototype of RB (RB1) and eight
      participants used the second prototype of RB (RB2). RESULTS: The results
      indicated that the functionality was improved owing to the end-user evaluations.
      Therefore, we confirmed the content validity of the proposed ULCEAT method.
      CONCLUSION: In this study we confirmed the validation of the ULCEAT methodology
      by applying it in retrospect to RB using development process. This method will be
      used for the development of Life-support robots and prototype assistive
      technologies.

PMID- 26294544
TI  - ICT services for prolonging independent living of the elderly with cognitive
      impairments - IN LIFE concept.
AB  - Older people with cognitive impairment need support in their everyday living. IN
      LIFE an EC co-funded project aims to organize large-scale and multi-country pilot
      applications, by providing interoperable, open, personalised and seamless ICT
      solutions that support older persons in all key home activities, communication,
      health maintenance, travel, mobility and socialisation tasks, with novel,
      scalable and viable business models. 

PMID- 26294545
TI  - A conceptual framework related to ICT-AT competence development: The theoretical
      foundations of ENTELIS.
AB  - This paper provides an overview of the construction of a conceptual framework
      regarding ICT-Assistive Technology (ICT-AT) competence development, designed to
      gain awareness of the elements involved and to facilitate the understanding and
      exchange among stakeholders of the ENTELIS (European Network for Technology
      Enhanced Learning in an Inclusive Society) project. The framework was designed
      based on the basic principles of Activity Theory, which however have been adapted
      and adjusted to the project's objectives. Hence, it includes a map of actors and
      other parameters functioning in a person surrounding "ecosystem", and it allows
      us to understand and map roles, expectations, barriers, as well as to devise
      solutions to tackle digital divide. Taking as a starting and central point the
      person and his/her wish to self-determination and fulfilment (quality of life)
      and the related needs, it provides a map of how the various concepts and
      variables interact within the theoretical and methodological perspective of the
      collection, description and assessment of experiences in ICT-AT education and
      competences development of persons with disabilities (PwD) of all ages. The
      conceptual framework represents two interacting learning activity systems: (a)
      the internal system of the end-user, which includes the end-user and his/her
      needs, the setting where learning takes place and the other actors involved, and
      (b) the external system, which embraces the internal system but also wider issues
      of policy and practice and experiences and 'actors' that contribute to the
      development and use of ICT and ICT-AT skills in all areas of life. The elements
      of these systems and their interaction provide the basis for analysing
      experiences and advancing knowledge relevant for bridging the digital divide. 

PMID- 26294546
TI  - Views and considerations on ICT-AT competences development within the ENTELIS
      project: The Case of Cyprus.
AB  - This submission presents part of the EU funded project ENTELIS (European Network
      for Technology Enhanced Learning in an Inclusive Society), which aims to address
      issues of digital divide and digital equity for people with disabilities of all
      ages, and to increase participation and social inclusion. This paper presents the
      main activities and outcomes of the research work package of the project (WP3),
      from one of the partner countries, Cyprus. The aim of the conducted research was
      to identify the conceptions and beliefs of end-users, trainers, and
      service/technology providers and professionals, on the multifaceted relation
      between ICT/ICT-AT (Information Communication Technology - Assistive Technology)
      and learning of technology. Data collection involved the development and
      administration of three semi-structured interview protocols, one for each group
      of participants, in five different European countries. Results have been compiled
      to develop a State-of-Art Report on ICT and ICT-AT education and learning,
      highlighting the main trends, as well the main present barriers, emergent and
      future needs in terms of analysis, acquisition and reinforcing of digital
      competences bridging the worlds of education and work. 

PMID- 26294547
TI  - Mainstream ICT Can Support Children and Adolescents with ADHD and/or Autism in
      Their Everyday Activities.
AB  - This exploratory case study investigated how ICT can support children with ADHD
      and/or autism and their families in their daily activities. We focus in
      particular on the suitability of mainstream technology for such support. Two
      cases are presented, and implications for practice are discussed. The findings
      indicate that mainstream ICT can be of assistance, but that its implementation
      can be challenging in particular in regards to elaborate technological setup
      routines, vulnerability to malfunction, and time needed for assessment, training
      and follow-up. The work continues in the ongoing R&D-project Is it possible?. 

PMID- 26294548
TI  - E-inclusion: Digital equality - young people with disabilities.
AB  - The United Nations' position is that digital access is a matter involving
      equality between groups of people, the securing of democratic rights, and equal
      opportunities for all citizens. This study investigates digital equality in
      school and leisure between young people with and without disabilities. A cross
      sectional design with group comparisons was applied. Participants were young
      people (10-18 years of age) with disabilities (n=389) and a reference group in
      about the same ages. Data were collected by a survey focusing on access to and
      engagement in ICT activities in school and during leisure time. The results
      demonstrated young people with disabilities had restricted participation in
      computer use in educational activities, in comparison to young people in general.
      During leisure time young people with disabilities had a leading position
      compared to the reference group with respect to internet use in a variety of
      activities. Beneficial environmental conditions at home (and the reverse in
      schools) are discussed as parts of the explanation for the differing engagement
      levels at home and in school, and among young people with disabilities and young
      people in general. CONCLUSION: Schools need to prioritise use of ICT by young
      people with disabilities.

PMID- 26294549
TI  - Introducing LUDI: a research network on play for children with disabilities.
AB  - This paper presents LUDI, an interdisciplinary network of research centred on the
      topic of play for children with disabilities. The primary aim of the network is
      to ensure the theme is given the widest recognition as an independent field of
      research and intervention. Currently, the network comprises over 80 researchers
      and practitioners from 27 European countries. It is funded by the EU COST
      Programme through the means of an interdisciplinary Action started in May 2014
      and lasting four years. The present contribution will discuss the scientific and
      social background and their implications that lead to the creation of the
      network, activities carried out during the first year of the Action and
      introduces the expected results of the ongoing activities. 

PMID- 26294550
TI  - Feasibility of using MIRA with adult patients presenting with upper limb motor
      dysfunction post neurological damage.
AB  - Computer-based technology is an emerging modality to facilitate upper limb
      rehabilitation post neurological damage. A feasibility project using MIRA
      technology in an adult outpatient neurophysiotherapy service was conducted. Ten
      patients trialled nine MIRA games that promoted discrete and continuous
      unilateral and bilateral upper limb movements. The effect of MIRA use on usual
      service operation as well as any adverse events was noted. Patient views of using
      MIRA were explored through self-reported questionnaires. For six patients,
      comparison of amount and frequency of active upper limb exercises using MIRA and
      typical prescribed upper limb exercises was made. Use of MIRA did not negatively
      affect service operation and was not associated with any adverse event reporting.
      The majority of patients enjoyed using MIRA and felt that it was a useful
      modality to supplement existing prescribed upper limb exercises. Those with
      previous experience of technology expressed the most positive feedback. There is
      evidence that MIRA tasks may facilitate intensive repetitive upper limb
      movements, although some patients reported in-exercise discomfort. In conclusion,
      it was feasible to use MIRA with adult patients post neurological damage
      presenting with upper limb motor dysfunction, particularly those patients with
      proximal upper limb motor dysfunction previously familiar with computer use or
      gaming experience. 

PMID- 26294551
TI  - Measuring Benefits of Telepresence robot for Individuals with Motor Impairments.
AB  - The telepresence robot is a type of technology used to socialize with people in
      remote places. If this technology is efficient, it could be an alternative means
      to attend social activities such as going to school and work for people who have
      difficulty to go out because of motor impairments. The objective of this study is
      to investigate the effect of using a telepresence robot in the marketplace by
      individuals with motor impairments. Three participants were involved with trial
      use for attending university courses for a month and the initial results are
      shown. 

PMID- 26294552
TI  - Usability of a New Writing Assistive Device for Persons with Cervical Spinal Cord
      Injury.
AB  - The hand function for persons with cervical spinal cord injury (PCSCI) is most
      frequently cause difficulties in leading normal lives. The purpose of this study
      was to test the usability of a new writing assistive device (NWAD) for PCSCI. To
      access its usability, the authors design usability testing method and test the
      NWAD to five individuals with cervical spinal cord injury. From the usability
      testing, we have found number of issues that lead us to key design concept about
      developing the NWAD. The NWAD will be redesigned based on the result of the
      present study. We expect that the NWAD will help PCSCI use their affected hand
      better and improve the level of independence and quality of life. 

PMID- 26294553
TI  - Assistive Technology as an artificial intelligence opportunity: Case study of
      letter-based, head movement driven communication.
AB  - We studied an artificial intelligent assisted interaction between a computer and
      a human with severe speech and physical impairments (SSPI). In order to speed up
      AAC, we extended a former study of typing performance optimization using a
      framework that included head movement controlled assistive technology and an
      onscreen writing device. Quantitative and qualitative data were collected and
      analysed with mathematical methods, manual interpretation and semi-supervised
      machine video annotation. As the result of our research, in contrast to the
      former experiment's conclusions, we found that our participant had at least two
      different typing strategies. To maximize his communication efficiency, a more
      complex assistive tool is suggested, which takes the different methods into
      consideration. 

PMID- 26294554
TI  - Development of Integrated Public Administration Custom Services in Hungary.
AB  - The paper is a case-study introducing a national project in Hungary establishing
      a countrywide public administration customer service system where accessibility
      was a key issue. Starting from the concept the paper describes the methods and
      organisational background how accessible design was integrated in the planning
      method and gives a feedback of site experiences. 

PMID- 26294555
TI  - Assistive Technology: Creating and Engaging Collaborative Communities.
AB  - This paper outlines the remit of the UK Engineering and Physical Sciences
      Research Council KT-EQUAL (Knowledge Transfer for Extending Quality of Life for
      older and disabled people) programme. Case examples drawing on the range of
      activities undertaken by KT-EQUAL highlight where assistive technology
      developments have been facilitated, the value of network activities and an
      underpinning model of engagement and collaboration. Given an increasing emphasis
      on the impact of research the model and innovative approaches deployed by KT
      EQUAL are even more crucial in future developments which aim to ensure that
      research can be used to benefit society. 

PMID- 26294556
TI  - Knowledge Exchange: selecting research opportunities through estimation.
AB  - A systematic way to select new ideas for research and development between two
      organisations is reported. It was applied to ideas that were generated from acute
      clinical settings by Occupational Therapists with a view to collaborate with
      nearby university academics from many disciplines. The process, assessment
      factors, use of ordinal scales with thresholding and an arbitrary formula are
      described. Challenges in the approach are discussed. Suitability for use by
      others in the AT field, other care related or even very different contexts is
      noted with some adaption and caveats. 

PMID- 26294557
TI  - A Unified Semantic Framework for the description of assistive technologies.
AB  - This paper presents the Semantic Alignment Tool, a unified, classified,
      ontological framework, for the description of assistive solutions that comprises
      information from different sources automatically. The Semantic Alignment Tool is
      a component of the Cloud4All/GPII infrastructure that enables users to add and/or
      modify descriptions of assistive technologies and align their specific settings
      with similar settings in an ontological model based on ISO 9999. The current work
      presents the interaction of the Semantic Alignment Tool with external sources
      that contain descriptions and metadata for Assistive Technologies (ATs) in order
      to achieve their synchronization in the same semantic model. 

PMID- 26294558
TI  - Building an effective ontology for assistive technology.
AB  - The aim of this paper was to develop and validate an ontology for one class of
      assistive technology (AT), namely physically controllable pointing devices, using
      the Delphi method. Six occupational therapists with AT expertise identified
      important items and categories to the pointing device prescription through a
      three-round, structured process consisting of responses to a series of
      questionnaires. The intraclass correlation coefficient (ICC) was used to assess
      the interrater reliability of items included in categories related to the
      pointing devices and to the user profile. During the first round, the ICC ranged
      from 0.19 to 0.97; this improved to ICCs ranging from 0.72 to 1.0 during the
      second round. A full consensus was reached by the experts during the final round
      which included 218 items, divided into five categories, for the pointing device
      list, and 168 items, divided into six categories, for the user profile list. This
      ontology is expected to help achieve a more systematic regulation of the AT
      field, leading to greater standardization and increased knowledge sharing. 

PMID- 26294559
TI  - Hybrid Instruction Method of Brush Strokes with Haptic Device.
AB  - This paper proposes an instruction method of brush strokes utilizing haptic
      devices. Focusing attention to the magnitude difference between the horizontal
      and the vertical in brush strokes, we introduced a position/force hybrid scheme
      for determining traction forces to be fed back to users: the horizontal component
      of the force was given to reduce the horizontal position deviation of a learner
      from an expert, and the vertical component was given as reaction forces of the
      expert-exerted forces. As an example, a bush stroke experiment was conducted for
      some Brahmi characters. 

PMID- 26294560
TI  - Improving quality of life through ICT for the facilitation of daily activities
      and home medical monitoring.
AB  - The potential of Information and Communication Technologies to improve the
      overall quality of life of all citizens cannot be underestimated. In particular,
      in the context of Ambient Intelligent environments, technological developments
      provide a great opportunity for the integration and the improvement of quality of
      life of people from vulnerable groups (patients, elderly, people with
      disabilities). In this context, the paper presents the aims, objectives and
      preliminary results of a National research project in Greece, named KRIPIS
      "Quality of Life", implemented by three research Institutes of FORTH, targeting
      post-heart attack elderly patients at their home environments. 

PMID- 26294561
TI  - Developing movement recognition application with the use of Shimmer sensor and
      Microsoft Kinect sensor.
AB  - Nowadays the development of virtual reality-based application is one of the most
      dynamically growing areas. These applications have a wide user base, more and
      more devices which are providing several kinds of user interactions and are
      available on the market. In the applications where the not-handheld devices are
      not necessary, the potential is that these can be used in educational,
      entertainment and rehabilitation applications. The purpose of this paper is to
      examine the precision and the efficiency of the not-handheld devices with user
      interaction in the virtual reality-based applications. The first task of the
      developed application is to support the rehabilitation process of stroke patients
      in their homes. A newly developed application will be introduced in this paper,
      which uses the two popular devices, the Shimmer sensor and the Microsoft Kinect
      sensor. To identify and to validate the actions of the user these sensors are
      working together in parallel mode. For the problem solving, the application is
      available to record an educational pattern, and then the software compares this
      pattern to the action of the user. The goal of the current research is to examine
      the extent of the difference in the recognition of the gestures, how precisely
      the two sensors are identifying the predefined actions. This could affect the
      rehabilitation process of the stroke patients and influence the efficiency of the
      rehabilitation. This application was developed in C# programming language and
      uses the original Shimmer connecting application as a base. During the working of
      this application it is possible to teach five-five different movements with the
      use of the Shimmer and the Microsoft Kinect sensors. The application can
      recognize these actions at any later time. This application uses a file-based
      database and the runtime memory of the application to store the saved data in
      order to reach the actions easier. The conclusion is that much more precise data
      were collected from the Microsoft Kinect sensor than the Shimmer sensors. 

PMID- 26294562
TI  - Developing movement therapy application with Microsoft Kinect control for
      supporting stroke rehabilitation.
AB  - The topic of this article and work was to create an application for movement
      therapy, which can help the rehabilitation of stroke patients. The application
      makes it possible to make unique exercises for different patients, adapting to
      the special personal needs. The developed real time gesture analyzing algorithm
      works in the background of the application, which has not yet spread on the field
      of medical devices. I deal with one part of this wide field in my dissertation,
      with the rehabilitation gesture analyzing. The data received from the Kinect
      sensor is processed by a location based gesture analyzing algorithm, and the
      results show that the software is suitable for the improvement of the
      rehabilitation process. It was a key aspect to create a simple interface. I
      achieved this with the use of the C# language and WPF technology. 

PMID- 26294563
TI  - Users' Perception and Readiness of the eChez-Soi In-Home Telerehabilitation
      Platform.
AB  - This longitudinal preliminary study aims to describe the components and features
      of the eChez-Soi home-based telerehabilitation platform, and present preliminary
      results on practitioners' readiness for and perception of its usability. Four
      patients receiving chemotherapy treatments for lung cancer followed an 8-week
      home-based telerehabilitation program with the new eChez-Soi platform and four
      healthy adults used it for 2 weeks. The users' perception was very good, with an
      overall satisfaction rate of 4.6+/-0.4 (max. score=5) for the patients, 4.8+/-0.2
      for the healthy adults and 4.4+/-0.3 for the practitioners. Total practitioner
      telehealth readiness was 73.5+/-9.1 (max score=85), suggesting that certain
      items, for at least one practitioner, may adversely impact the use of telehealth.
      These preliminary results support the usability of this new platform and suggest
      that practitioner telehealth readiness is reinforced with experience. 

PMID- 26294564
TI  - Structures, snacks, sprints, and socialising: strategies to increase writing
      output for AT Practitioners.
AB  - Assistive Technology Practitioners are often engaged in research, evaluation and
      other reporting activities, but struggle to complete publications reporting the
      work. This paper presents three evidence-based strategies for increasing writing
      output: (i) write to a structure; (ii) use snacks and sprints, and (iii) get
      social. These strategies may be useful for AT Practitioners wanting to increase
      their writing output. 

PMID- 26294565
TI  - Developing User-Centered Continuous Professional Education for ATD Service
      Personnel.
AB  - BACKGROUND: Finnish Assistive Technology Device Service centers raised the
      question about education to the full-time workers of ATD Services. They nominated
      a group which included representatives of universities, ATD Service centers and
      national authorities. This small group drew up background questionnaires
      concerning the education, its content and length. Three universities started the
      education, the aim of which was to learn new methods to develop their own work,
      learning by doing at work with their superiors. This continuous professional
      education corresponded to 30 ECTS credits and lasted 10 months. RESULTS: Based on
      the feedback from the guiding group of CPE, students and their superiors, this
      type of education is needed. It met its goals by giving students methods to
      develop their work and broaden their view on ATD service when having discussions
      with other experts. Continuous professional education needs to be developed
      further and it could also be part of joined European education with national
      elements.

PMID- 26294566
TI  - A Participatory Research Approach to develop an Arabic Symbol Dictionary.
AB  - The purpose of the Arabic Symbol Dictionary research discussed in this paper, is
      to provide a resource of culturally, environmentally and linguistically suitable
      symbols to aid communication and literacy skills. A participatory approach with
      the use of online social media and a bespoke symbol management system has been
      established to enhance the process of matching a user based Arabic and English
      core vocabulary with appropriate imagery. Participants including AAC users, their
      families, carers, teachers and therapists who have been involved in the research
      from the outset, collating the vocabularies, debating cultural nuances for
      symbols and critiquing the design of technologies for selection procedures. The
      positive reaction of those who have voted on the symbols with requests for early
      use have justified the iterative nature of the methodologies used for this part
      of the project. However, constant re-evaluation will be necessary and in depth
      analysis of all the data received has yet to be completed. 

PMID- 26294567
TI  - Development of Augmentative and Alternative Communication Assessment Tools for
      Patients with ALS.
AB  - ALS patients usually use augmentative and alternative communication tools to
      communicate with other people, but the assessment tools, including the selection
      of an input switch, are very difficult to operate. In this study, we developed a
      novel device to measure the physical ability of patients to operate the input
      switch with a push lever. The study focused on the amount of pushing and the
      power required to operate the input switch, and the effectiveness was verified. 

PMID- 26294568
TI  - A User and Their Family's Perspective of The Use of a Low-Tech Vs A High-Tech AAC
      System.
AB  - This qualitative case study describes a 9-year-old child, diagnosed with
      homonymous hemianopia, left side weakness and seizures that has been followed by
      Access to Communication and Technology Unit in Malta for 5 years. The child
      previously used a communication book and now uses an iPad as a speech generating
      device. A semi-structured interview was utilised with the parent to explore
      preference for each AAC system and the reasons for it. The impact of each AAC
      system on the family and on the child's communication skills, and perceived
      barriers in the implementation of the AACs were also explored. The child's own
      experience using the AAC systems was also investigated using a structured
      interview format. Talking Mats was used to support the child's understanding of
      the questions and to explore her perspectives on the two AAC systems using Yes-No
      responses. The parent interview was analysed thematically and represented
      visually using a thematic network. This was compared with child responses. Four
      organising themes emerged including barriers, benefits, facilitators, and
      expectations. Specific barriers included self-funding in order to provide the
      child with the best fit high-tech AAC. Perceived benefits for both AAC systems
      were that it increased her communicative intent. The child's mother perceived
      access to increased vocabulary and capacity for sentence building, operational
      autonomy as well as voice output as a benefit of the SGD. The child's results
      indicated a preference for the high-tech AAC because she found it easier to
      navigate than the low-tech AAC. 

PMID- 26294569
TI  - Daily activity patterns of people provided with a dynamic arm support.
AB  - Dynamic arm supports are provided to support activities of daily living in people
      with limited upper extremity function. A cross-sectional study was performed in
      the Netherlands involving people who were provided with a dynamic arm support in
      2012-2013. An adapted version of the Life-Habits questionnaire was used to assess
      daily activity patterns. Twenty-three subjects filled in the questionnaire. Tasks
      people perform themselves in daily life include tasks as eating, drinking, and
      communication tasks. Participants vary in the need for assistance in order to
      perform certain tasks. This individual character of daily activity performance is
      important to bear in mind during the provision of dynamic arm supports. More
      complex tasks in the field of personal care and household are often performed by
      caregivers. These are regarded a challenge for the field of assistive technology
      and/or robotics. 

PMID- 26294570
TI  - Possibilities of the ErgoScope high fidelity work simulator in skill assessment,
      skill development and vocational aptitude tests of physically disabled persons.
AB  - The aim of this paper - based on the extensive experiences of the authors gained
      by using one particular work simulator - is to present some promising
      possibilities of the application of this (and any other similar) work simulator
      in the field of skill assessment, skill development and vocational aptitude tests
      of physically disabled persons. During skill assessment and development, as parts
      of the therapy, the focus is on the disabled functions. During vocational
      aptitude tests, however, the focus is already on the functions that remained
      intact and therefore can be the basis of returning to work. Some factual examples
      are provided to realize the proposed possibilities in practice. 

PMID- 26294571
TI  - The Importance of Technical Devices in the Self-care of Upper Limbs Amputees.
AB  - The National Institute of Medical Rehabilitation (NIMR) is engaged in the
      rehabilitation of posttraumatic patients, including also attending traumatic
      cases with amputated upper limbs. The lack of upper limbs is a great obstacle in
      essential functioning for the injured, and that is why we give high priority to
      planning, constructing and individually adopting appliances for aiding everyday
      life. Special literature gives distinguished attention to operative techniques
      and the possibilities of prosthetic devices, but no professional articles present
      any special devices needed for discharging everyday vital functions. The purpose
      of this lecture is to present the results of our follow-up examination aimed at
      upper limbs amputees reeducated since 1994 at the NIMR (9 patients). Case studies
      conclude that the prosthetic care plays a surprisingly small part in the self
      sufficiency of the injured. Claims to individual appliances are already more
      considerable but these cannot be obtained in normal commerce because of
      unprofitable production in view of users so few in number. 

PMID- 26294572
TI  - Eye-tracking and EMG supported 3D Virtual Reality - an integrated tool for
      perceptual and motor development of children with severe physical disabilities: a
      research concept.
AB  - Letting children with severe physical disabilities (like Tetraparesis spastica)
      to get relevant motional experiences of appropriate quality and quantity is now
      the greatest challenge for us in the field of neurorehabilitation. These motional
      experiences may establish many cognitive processes, but may also cause additional
      secondary cognitive dysfunctions such as disorders in body image, figure
      invariance, visual perception, auditory differentiation, concentration, analytic
      and synthetic ways of thinking, visual memory etc. Virtual Reality is a
      technology that provides a sense of presence in a real environment with the help
      of 3D pictures and animations formed in a computer environment and enable the
      person to interact with the objects in that environment. One of our biggest
      challenges is to find a well suited input device (hardware) to let the children
      with severe physical disabilities to interact with the computer. Based on our own
      experiences and a thorough literature review we have come to the conclusion that
      an effective combination of eye-tracking and EMG devices should work well. 

PMID- 26294573
TI  - Service Dogs for People with Spinal Cord Injury: Outcomes Regarding Functional
      Mobility and Important Occupations.
AB  - No research using standardized tests based on direct observations along with
      longitudinal studies have shown the effects of service dogs on persons with
      mobility impairment. Our research objectives were to document the consequences of
      the use of the service dog on wheelchair propelling, grasping objects, shoulder
      pain, occupational performance, reintegration into normal living and psychosocial
      impacts for people with spinal cord injury (SCI). A cross sectional study was
      conducted with 45 males and 21 females with SCI (average age = 41.2). They were
      assessed in their homes and their communities, two to five years after they
      received their service dogs. Observations were based on four testing methods. An
      ongoing longitudinal study is reported, based on 9 months (n = 8 to 16) of data
      from four standardised questionnaires. Results demonstrate that services dogs are
      an efficient assistive technology for persons with SCI. 

PMID- 26294574
TI  - Support Services for Informal Caregivers: First Results of Expert Interviews with
      Providers in the City of Vienna.
AB  - The burden of informal caregivers can be potentially reduced with support
      services targeting them primarily. But when it comes to the utilization of such
      services, there are still barriers on the side of suppliers and demanders that
      leads to the fact that too less concerned people are making use of it. Expert
      interviews were done with offering institutions in the City of Vienna to find out
      more about the types of offered support services, consideration of special
      circumstances, utilization behavior, awareness, benefit, costs and future
      development. This paper is presenting the preliminary results of the data
      analysis of the first round of interviews that shows the status quo of
      utilization of support services for informal caregivers in the City of Vienna. 

PMID- 26294575
TI  - Acceptance Criteria of Ambient Assistant Living Technologies.
AB  - Ambient Assisted Living (AAL) is a growing field resulting from aging populations
      in the majority of the well-developed regions of the world. AAL technologies aim
      at supporting independent living at home and therefore, include a wide variety of
      innovations. However, even though AAL technologies are on the rise, the
      acceptance of them among the elderly population is still low. In order to
      elaborate acceptance criteria, the state of the art on opinions and perceptions
      of elderly people about AAL technologies, is summarized. A total of eleven
      acceptance criteria are excerpted from this and a diagram is created to show
      their connections. This information can be helpful for the developers of future
      AAL technologies, so that they have a better idea of aspects they have to
      consider to improve the acceptance of their technology. The excerpted criteria
      are illustrated based on the FEARLESS - life comfort system, which is an image
      based fall detection system as an example for a recently developed AAL
      technology. 

PMID- 26294576
TI  - RelaxedCare - Connecting people in care situations: User involvement to collect
      informal caregivers needs.
AB  - "How is my mom doing right now?" Answering this question in a quick, clear way
      without the need of calling or stopping by could take away a lot of stress from
      informal caregivers. The RelaxedCare system aims to develop a solution built upon
      an existing AAL platform, using a multi-level pattern recognition approach to
      detect the current state of an assisted person, and then to communicate the state
      in a pervasive and unobtrusive way (i.e. lava lamp, smartphone widget, picture
      frame) to the caregiver. For the development of the RelaxedCare system a user
      centred design approach has been chosen applying especially the ISO 9241-210 [3]
      and the user-inspired innovation process [2]. A first technical prototype was
      evaluated with representative end users in lab trials via usability testing to
      find out, how the generated ideas match with the end user needs. The results show
      that the project is on the correct path. The majority of participants approved,
      that the RelaxedCare system supports the informal caregiver in a worry-free way
      to care for the assisted person (thus allowing the older generation to live
      longer in their own homes). 19 of 25 participants felt an advantage by using the
      system in their care situation in general. Overall 18 of them rate the advantage
      of the usage at home positively and 20 of them rate the usage positively, if they
      use it on the way. Also interesting is that in total 19 participants could
      imagine, that there would be an improvement of the care situation for their own
      family through the RelaxedCare system. 

PMID- 26294577
TI  - YouDo - we help! - An Open Information and Training Platform for Informal
      Caregivers.
AB  - The number of people in need of care increases constantly, and in the coming few
      years many seniors will depend on their close relatives for their care needs.
      These relatives very often need support to fulfill their role as informal
      caregivers. The YouDo prototype presented in this paper aims to provide special
      training programs for informal caregivers in order to help them to improve the
      quality of their nursing. This work illustrates first development concepts, used
      methods and techniques towards a modular, extensible and user adaptable
      multimodal information and training platform. 

PMID- 26294578
TI  - Modes of independence while informal caregiving.
AB  - This paper is about understanding and conceptualizing the notion of independence
      in the context of caregiving. Based on the current studies and on our
      ethnographic and design research in an AAL project (TOPIC) we introduce a model
      of independence consisting of four dimensions: action, finance, decision, and
      emotion. These interrelated dimensions are described and discussed in the setting
      of informal caregiving. Some additional examples are shown to illustrate how to
      reduce the dependence of informal caregivers before concluding the paper. 

PMID- 26294579
TI  - Goal setting for cerebral palsy children in context therapy: improve reliability
      when linking to ICF.
AB  - The linking process of information to ICF is a common task in different
      strategies used in rehabilitation practise but is a time consuming process mainly
      due to reliability issues. This work aims to developed additional rules to those
      already published in order to improve reliability of the linking process to ICF.
      The results are encouraging and this work could help to develop information
      technologies tools for facilitate this process. 

PMID- 26294580
TI  - Bioimpedance based monitoring system for people with neurogenic dysfunction of
      the urinary bladder.
AB  - Patients with impaired bladder volume sensation have the necessity to monitor
      bladder level in order to avoid urinary tract infections and urinary reflux that
      can lead to renal failure. In this paper the the effectiveness of an embedded and
      wearable solution for bladder volume monitoring using the bioimpedance
      measurement is tested. Data are streamed real-time using Bluetooth wireless
      technology. The bioimpedance measurements on a healthy subject prove the
      effectiveness of the proposed solution. In the future the system will be
      evaluated in real world scenarios with patients affected by spinal paralysis and
      bladder neurogenic dysfunction. 

PMID- 26294581
TI  - Advancing Telemedicine Services for the Aging Population: The challenge of
      Interoperability.
AB  - We reflect on our experiences in two projects in which we developed interoperable
      telemedicine applications for the aging population. While technically data
      exchange could be implemented technically, uptake was impeded by a lack of
      working procedures. We argue that development of interoperable health technology
      for the aging population should go accompanied by a thorough study into working
      protocols by consulting all end-users and stakeholders. 

PMID- 26294582
TI  - PUMA project: Active involving of end users to achieve a smart solution to
      prevent pressure ulcer.
AB  - This paper shows the benefits to include spinal cord injury users and the other
      stakeholders during the development of a new system to prevent pressure ulcers.
      The complementary of information has been key and has enhanced the possibility to
      achieve market acceptance and introduction. 

PMID- 26294583
TI  - Effectiveness of IPMS tool for handling chronic low back pain with sitting
      workplace employees.
AB  - Effectiveness of IPMS tool for handling chronic low back pain with sitting
      workplace employees. 

PMID- 26294585
TI  - Example of the application of the PERSONA methodology in the definition of needs
      and requirements for the WeTakeCare system.
AB  - In user-centred design and marketing, personas are fictional characters created
      to represent the different user types that might use a site, brand, or product in
      a similar way [1]. As in other projects, the main application and use value of
      the persona approach in WeTakeCare project has been to depict and thus make
      "vivid" the characters and the milieus created and selected. It has helped to
      better understand and communicate the differences among the potential users. It
      has also helped to understand the heterogeneity and diversity of the users' lives
      and to focus on how to meet their actual needs [2]. 

PMID- 26294586
TI  - On the Use of Dance as a Rehabilitation Approach for Children with Cerebral
      Palsy: A Single Case Study.
AB  - Cerebral Palsy (CP) is the most common motor disability in childhood. It is a
      group of permanent disorders that affect child development causing disorders of
      movement and posture and activity limitations. The impairment of psychomotor
      skills of children with Cerebral Palsy is attributed to a permanent alteration
      occurred in non-progressive brain development of the fetus or nursing infant.
      Some motor related symptoms can be treated using proper physical therapy.
      However, one of the biggest problems of the usual physical therapy is adherence
      to therapy. Ballet can be an alternative or a complement to physiotherapy, with
      the added attraction of not being part of a to therapy, but a fun activity with
      the extra reward associated with the realization of an artistic activity. For
      some years the ballet is used as therapeutically valuable for both children with
      cerebral palsy: Intensive ballet training can generate changes in the
      sensorimotor cortex. Ballet is characterized by a complex process of movements
      that have to be in a musical rhythm (hence have to be precise), in which there is
      an overall coordination of the muscles. It is also a highly motivating and
      rewarding activity that allows many children with CP sharing the activities of
      their peers without special needs. Objective measurements of the Full Port de
      Bras movement has been chosen as an index of improvement. The results shows
      progressive improvements of the execution in a single case. 

PMID- 26294587
TI  - Effect of Tire Pressure to Physical Workload at Operating a Manual Wheelchair.
AB  - It is often experienced that low tire pressure of the wheelchair not only
      increases running resistance, but also reduces parking brake performance. In this
      study, the required driving forces for different tire pressures were
      experimentally measured and evaluated. It was indicated from the result that the
      wheelchair with proper tire pressure could be run with less workload of
      wheelchair-user. Then it was also indicated that the wheelchair with a lower tire
      pressure needed more workload of wheelchair-user even on hard level surface. 

PMID- 26294588
TI  - Conceptualizing Everyday Mobility of Older People as Basis for the Development of
      a Pedestrian Assistance System.
AB  - For older persons, everyday mobility is an important aspect of living an
      independent and self-determined life. Especially with increasing age most of the
      everyday ways in urban areas are covered by foot. The more severe is the fact
      that older pedestrians are among the most vulnerable road users. This is the
      starting point of the research group FANS aiming for developing a pedestrian
      assistance system for older road users. Therefore, it is necessary to understand
      the difficulties older pedestrians encounter. In order to do so, everyday
      mobility of this group will be conceptualized using the Constraints Approach by
      Hagerstrand and the Theory of Structuration by Giddens. Currently, two focus
      groups have been carried out that have been analyzed according to Hagerstand's
      and Gidden's considerations. Hereinafter, the category system that has been
      derived from the theoretical considerations will be presented and an outlook will
      be given. 

PMID- 26294589
TI  - Advanced work capacity testing.
AB  - The aim of this study is to describe an accurate work capacity testing which can
      be used in the industry, as well as in rehabilitation process. The first part of
      this paper is dealing with the NIOSH lifting equation, which is a tool used by
      occupational health and safety professionals. The second part of this paper
      summarizes the features and applications of the "ErgoScope" work simulator.
      Static and dynamic strength of upper and lower limbs, as well as whole body
      efforts can be measured. The equipment makes it possible to evaluate pushing,
      pulling, lifting and carrying activities comprising reaching, bending and
      stooping movements. In the third part of this paper we demonstrate handgrip force
      data recorded using the "ErgoScope" work simulator comparing with handgrip force
      data published in the literature. "ErgoScope" work simulator is capable to
      measure handgrip and pinch forces, suitable to evaluate fine motor skills, hand
      and finger dexterity, as well as reaction times. 

PMID- 26294590
TI  - A Functional Analysis Of An Assistive Device Information Database in Flanders: A
      Qualitative Study.
AB  - Since 1989-1990, Vlibank is the Flemish AT information database managed by the
      Flemish government and aims to have a complete overview of AT devices in
      Flanders. The growing AT market increases the need for unbiased information on
      AT. However, maintaining and keeping a database up-to-date is a very challenging
      task. Because of recent changes in policy, the Flemish government needs to be
      able to reimburse a bigger group of AT devices, but also the changing needs of a
      larger group of people, regardless of their age. Because the crucial role of an
      AT information database in the selection of AT devices and the effectiveness of
      the service delivery, a functional analysis of an online information database is
      made. This paper describes the qualitative part of the study, in particular the
      focus groups that were held to gather views of three groups of stakeholders.
      Preliminary results indicate that there is consensus on the information needs
      next to product information and on the use of generic questions as a selection
      tool for AT devices. The biggest issue raised is the difficulty of keeping an
      information database up-to-date, especially for individualized devices. All
      participants, except one, are very wary of the use of user ratings and reviews. 

PMID- 26294591
TI  - Virtual Reality in Assessing the Supportive Environment that Promotes
      Navigability of Persons with Alzheimer's disease.
AB  - Spatial cognition and representation in persons with Alzheimer's disease (AD) is
      usually impaired, alongside with cognitive impairment. It is important to provide
      the supportive environments that support their ability of wayfinding to maintain
      the daily activities and autonomy. The aim of this paper is to emphasize how
      Virtual Reality (VR) system is used to assess the improved environmental design
      that promotes spatial navigability in persons with AD. The importance of
      supportive environments and significant studies that used VR in the wayfinding
      interventions is presented. The paper proposed a strategy to use Virtual
      Environment (VE), replacing the traditional assessment in the design development
      phase of supportive environment. Results from the preliminary valuation using
      interview show positive feedback by the medical experts, since immersive VE
      allows the experience being in actual environment. Also, the proposed strategy
      may reduce the costly and time-consuming design process. An evidence-based
      validation involving persons with AD will be conducted to investigate the
      effectiveness of this assessment strategy by comparing the individuals'
      navigational performances in both real and VE. 

PMID- 26294592
TI  - Bridging the gap between high school and University studies for student with
      disability.
AB  - The choice of the university program represents an important and difficult step
      for a large part of high school students, especially for those who have to change
      city and lifestyle to follow their ambitions. In particular, for students with
      disabilities this choice is even more complicated due to their specific needs
      concerning both their educational and everyday life. In order to bridge the gap
      between high school and the University of Pisa, supporting the students during
      the selection of the program and their stay in Pisa, this paper presents a new
      model for matching the needs of the students and the existing services in Pisa,
      with particular attention to those with disabilities. It is based on
      questionnaires to assess the needs of the students and an accessible website to
      make available information about places and services offered in Pisa and its
      surrounding. 

PMID- 26294593
TI  - Real-time Pedestrian Crossing Recognition for Assistive Outdoor Navigation.
AB  - Navigation in urban environments can be difficult for people who are blind or
      visually impaired. In this project, we present a system and algorithms for
      recognizing pedestrian crossings in outdoor environments. Our goal is to provide
      navigation cues for crossing the street and reaching an island or sidewalk
      safely. Using a state-of-the-art Multisense S7S sensor, we collected 3D
      pointcloud data for real-time detection of pedestrian crossing and generation of
      directional guidance. We demonstrate improvements to a baseline, monocular-camera
      based system by integrating 3D spatial prior information extracted from the
      pointcloud. Our system's parameters can be set to the actual dimensions of real
      world settings, which enables robustness of occlusion and perspective
      transformation. The system works especially well in non-occlusion situations, and
      is reasonably accurate under different kind of conditions. As well, our large
      dataset of pedestrian crossings, organized by different types and situations of
      pedestrian crossings in order to reflect real-word environments, is publicly
      available in a commonly used format (ROS bagfiles) for further research. 

PMID- 26294594
TI  - Occupational therapy research on technology in Scandinavia. A research proposal.

PMID- 26294595
TI  - Development of Communication Assistive Technology for Persons with Deaf-Blindness
      and Physical Limitation.
AB  - The purpose of this study was to develop a system that will provide communication
      assistance to persons with deaf-blindness and physical limitation, so that they
      will be able to communicate with others without the help of an interpreter. With
      this communication system, a person with deaf-blindness and physical limitation
      uses a control switch to perform input operations based on the duration of the
      operating time and combination of long and short pulses. When the input is
      correctly performed, the user receives a feedback from the tablet computer as
      vibratory stimuli. Similarly, the message that other person's input with a
      Bluetooth keyboard is transmitted to the user as vibration stimuli. Following the
      development, we conducted a one-year assessment of the developed communication
      system in an actual environment with the cooperation of one person with deaf
      blindness and physical limitation. . We confirmed that our developed system was
      useful for such a person, and understood that we must improve upon several
      aspects. We shall pursue further study, and will aim at providing a better
      communication environment for persons with deaf-blindness and physical limitation
      in future. 

PMID- 26294596
TI  - Communication Robots for Elderly People and Their Families to Support Their Daily
      Lives - Case Study of Two Families Living with the Communicaton Robot.
AB  - The aim of this project is to analyze how two families (one is living with a
      senior with physical disabilities and the other is living with seniors) feel
      about using the human-type communication robot "Palro" and what they demand for
      the improvement through their 3 weeks usage. All of them liked Palro and its
      programs, but needed some new programs. They pointed out that Palro sometimes had
      problems in the facial or voice recognition systems. Palro is useful in the area
      of self-care and social isolation. 

PMID- 26294597
TI  - Development of safety concept of electric wheelchair driving support system based
      on assessment of risk.
AB  - In this research, we pay attention to the electric wheelchair driving support. We
      look at the functional safety of the electric wheelchair. Based on intrinsically
      safe electric wheelchair, we add driving support system to increase functional
      safety. The driving support system processes the environmental information sensor
      data including the 3D laser Range scanner and biological monitoring sensor data
      including electrooculogram, and assists avoidance of dangerous objects. We have
      developed safety concept that based on assessment of risk. 

PMID- 26294598
TI  - Technologies Closely Connected to Citizens' Health - Methodology, User
      Involvement and Health Care Technologies.

PMID- 26294599
TI  - A Brief Introduction of Assistive Technology Service Delivery System in Republic
      of Korea.
AB  - Social participation of People with Disability in Republic of Korea has been
      grown last few years. Also demand of Assistive Technology has been increased as
      well. Responding these needs, the public benefits of Assistive Technology Device
      in Republic of Korea in 2014 was USD 1.7 billion which had been increased by 27
      percent during the last five years. Despite an increase in the budget, effort to
      build Assistive Technology Service Delivery System (ATSDS) was not enough.
      Therefore, Ministry of Health and Welfare in Korea decided to build ATSDS in
      Republic of Korea in 2009. In this paper, the process of establishing ATSDS and
      2014 outcomes of ATSDS are presented in details. For more than six years efforts
      of establishing national-wide ATSDS, nine Assistive Technology Centers were
      actively running in their delivery of service in 2014. As of 2014 outcomes of
      ATSDS, 14,056 cases were delivered through nine Assistive Technology Centers. The
      presence of ATSDS proved increase in accessibility for Assistive Technology for
      People with Disability followed by improvement of the quality of life of them. 

PMID- 26294600
TI  - Comfort, Stability and Body Posture in Wheelchair Cushions: a preliminary study
      with able bodied subjects.
AB  - Long term wheelchair usage has been related to a number of problems, among which
      pressure ulcers are one of most concern. The design of wheelchair seat cushions
      has been of increasing interest among researchers, as it can influence seat
      interface pressure and user's comfort. The aim of this study was to investigate
      the subjects' perception comfort, stability and body posture of six different
      commercially available wheelchair cushions. The evaluation was through a
      questionnaire, where the subjects rate their perceptions on a ten point visual
      analog scale after staying seated in the cushion for two minutes. The results
      shows that the Roho<sup>TM</sup> aircell cushion was preferred by the users,
      while the least preferred one was the water cushion. Individuals' subjective
      perceptions may compliment objective data on seat interface pressure, thus
      contributing to a more complete view of the users' experience during wheelchair
      cushion usage. 

PMID- 26294601
TI  - Development of the SORRI-BAURU Posterior Walker.
AB  - This study aimed to report on the design and development of a low cost Reverse
      Walker through a participative development cycle with people undergoing
      rehabilitation. The creation and fundamentals of the concept are described, as
      well as the development of prototypes and their provision to subjects with
      mobility problems. The Reverse Walker benefits the user by promoting a more
      upright posture and favoring the development of postural balance. Enhancing the
      mobility of people with disabilities may benefit their independence, social
      participation and quality of life. 

PMID- 26294603
TI  - Multiple ANN Recognizers for Adaptive Recognition of the Speech of Dysarthric
      Patients in AAL Systems.
AB  - People suffering from neuromuscular disorders are one of the main target groups
      of speech-controlled Ambient Assisted Living systems. However, the speech of
      these patients is often distorted because of the dysarthric symptoms of the
      disease. The dysarthria is known to become worse as the disease progresses. We
      propose a framework for an adaptive speech recognition system that may be able to
      follow the slow deterioration of speech quality without risking the accuracy of
      the system from incorrect data. 

PMID- 26294602
TI  - Use of Robotic Pets in Providing Stimulation for Nursing Home Residents with
      Dementia.
AB  - Trial experiments utilized robotic pets to facilitate self-reliance in nursing
      home residents. A remote-control robot modeled clear and meaningful behaviors to
      elderly residents. Special attention was paid to its effects on mental and social
      domains. Employing the robot as a gaze target and center of attention created a
      cue to initiate a communication channel between residents who normally show no
      interest in each other. The Sony AIBO robot in this study uses commercially
      available wireless equipment, and all its components are easily accessible to any
      medical or welfare institution interested in additional practice of these
      activities. 

PMID- 26294604
TI  - Experiences of using powered wheelchair or powered scooter and accessibility in
      housings.
AB  - OBJECTIVE: To describe powered wheelchair (PW) and powered scooter (PS) users'
      experiences of accessibility and housing adaptions in their homes. METHOD: A
      qualitative research approach with focus group methodology was used. Four focus
      groups were created, with men and women as well as PW and PS users in different
      groups. Applying a descriptive approach, data were analysed according to the
      principles described by Krueger and Casey. FINDINGS: With a specific focus on how
      PW and PS and housing adaptations operate together, the findings of this paper
      formed two categories: "Possibility of receiving housing adaptations according to
      individual needs" and "Importance of receiving the correct type of PW and PS in
      relation to individual needs". CONCLUSION: It is vital to acknowledge the
      characteristics and requirements of PW and PS as well as housing adaptations in
      order to optimize the use of such devices in the home, as a prerequisite for
      independence, activity and participation. The provision of PW and PS and housing
      adaptations should be considered and planned simultaneously, applying an
      explicitly user-centred perspective. Additionally, the collaboration between the
      different actors involved should be improved.

PMID- 26294605
TI  - AAL@MEO: Interactive Digital-TV to Support Home Care.
AB  - This paper presents the evaluation of the AAL@MEO, an application to aggregate
      technological solutions supporting home care. This application is intended to be
      integrated in the MEO service, which is a Portuguese commercial service of
      Internet Protocol TV. The use of a TV set at home as the central interaction and
      communication system is advantageous for elderly users that do not have a close
      relationship with technological advances but are used to control their TV set.
      The results of the evaluation of the AAL@MEO show that elderly users are willing
      for new services and have a milder rejection towards the interaction with the TV
      set. However, the interaction mechanisms based on a remote control with multiple
      functions need further developments. 

PMID- 26294606
TI  - BrailleEasy: One-handed Braille Keyboard for Smartphones.
AB  - The evolution of mobile technology is moving at a very fast pace. Smartphones are
      currently considered a primary communication platform where people exchange voice
      calls, text messages and emails. The human-smartphone interaction, however, is
      generally optimized for sighted people through the use of visual cues on the
      touchscreen, e.g., typing text by tapping on a visual keyboard. Unfortunately,
      this interaction scheme renders smartphone technology largely inaccessible to
      visually impaired people as it results in slow typing and higher error rates.
      Apple and some third party applications provide solutions specific to blind
      people which enables them to use Braille on smartphones. These applications
      usually require both hands for typing. However, Brailling with both hands while
      holding the phone is not very comfortable. Furthermore, two-handed Brailling is
      not possible on smartwatches, which will be used more pervasively in the future.
      Therefore, we develop a platform for one-handed Brailing consisting of a custom
      keyboard called BrailleEasy to input Arabic or English Braille codes within any
      application, and a BrailleTutor application for practicing. Our platform
      currently supports Braille grade 1, and will be extended to support contractions,
      spelling correction, and more languages. Preliminary analysis of user studies for
      blind participants showed that after less than two hours of practice,
      participants were able to type significantly faster with the BrailleEasy keyboard
      than with the standard QWERTY keyboard. 

PMID- 26294607
TI  - Development of a Daily Life Support System for Elderly Persons with Dementia in
      the Care Facility.
AB  - Taking care for dementia persons with BPSD is burdening on caregivers. To reduce
      caregivers' burdens and improve dementia persons' quality of life, monitoring and
      communication intervention system has been proposed. A part of the system,
      wandering and falling down detection system has been developed. It is designed
      based on the requirement of the caregivers working in the care facility.
      Functional test was carried out and had positive impressions from the caregivers.

PMID- 26294608
TI  - Checking dwelling performance for Aging-in-Place.
AB  - About 90% of persons aged 55 and older would prefer to stay in their current
      residences as long as possible because older adults value their independence.
      However, aging-in-place is not always a choice. Recently, the Dutch government
      tightened the criteria for older adults to be admitted in a nursing home.
      Throughout the past 5 years TNO was requested by the trade association for
      building service contractors in the Netherlands to develop a number of tools for
      building service professionals. The 'dwelling check' was developed as a 'basic'
      check on the possibility for aging-in-place. A pilot study was conducted to
      assess the added value of the dwelling check for older adults. During this pilot
      study the occupants of over 200 dwellings were interviewed by 11 building
      services contractors using the dwelling check. Based on these interviews a
      personal advice was written. After which the interviewees were asked to evaluate
      this service, comprising the interview and written advice. The dwelling check
      contributed most to the awareness of and interest in possible alterations for
      aging-in-place. In a few cases the decision (17%) or even action (5%) was taken
      to make alterations. Overall the dwelling check was rated 8 out of 10 by the
      interviewees and may therefore be considered of added value. 

PMID- 26294609
TI  - Improving Assistive Technology Service by Using 3D Printing: Three Case Studies.
AB  - Assistive technology services are essential for adapting assistive devices to the
      individual needs of users with disabilities. In this study, we attempted to apply
      three-dimensional (3D) printing technology to three actual cases, and to study
      its use, effectiveness, and future applications. We assessed the usefulness of 3D
      printing technology by categorizing its utilization after reviewing the outcomes
      of these case studies. In future work, we aim to gather additional case studies
      and derive information on using 3D printing technology that will enable its
      effective application in the process of assistive technology services. 

PMID- 26294610
TI  - Education in care and technology, a facilitator of interdisciplinary research and
      development.
AB  - OBJECTIVE: Application of technology in care is hindered by two factors; a
      critical attitude of care professionals towards the use of technology as part of
      care delivery and a lack of knowledge of care practice by technology developers.
      Technological developments may provide adequate solutions to support care
      provision. The principles of user centred design and development, traditionally
      used in the development of assistive technology, may provide powerful tools to
      support care provision. Interdisciplinary research will be needed to take full
      benefit. Educational programs to support this development are lacking. Main
      content of this paper: Six organisations of higher education have taken the
      initiative to organize a training program to support professionals active in the
      care or in the technology domain that enables them to become involved in
      interdisciplinary research and development. RESULTS: a European program to
      educate a professional master in Care and Technology has been developed and is
      described in this paper. Accreditation of the program is initiated. CONCLUSION:
      Alumni of such a program may form a European network of professionals that are
      active in developing new solutions to support people with special needs and
      contribute to the generation of new business.

PMID- 26294611
TI  - New Tools to Convert PDF Math Contents into Accessible e-Books Efficiently.
AB  - New features in our math-OCR software to convert PDF math contents into
      accessible e-books are shown. A method for recognizing PDF is thoroughly
      improved. In addition, contents in any selected area including math formulas in a
      PDF file can be cut and pasted into a document in various accessible formats,
      which is automatically recognized and converted into texts and accessible math
      formulas through this process. Combining it with our authoring tool for a
      technical document, one can easily produce accessible e-books in various formats
      such as DAISY, accessible EPUB3, DAISY-like HTML5, Microsoft Word with math
      objects and so on. Those contents are useful for various print-disabled students
      ranging from the blind to the dyslexic. 

PMID- 26294612
TI  - Study on the Good Level of Legibility of Japanese Characters in Graphic Floor
      Signs.

PMID- 26294615
TI  - Assistive Technology. Building Bridges. Preface.

PMID- 26294616
TI  - Draft Genome Sequence of Pseudomonas sp. Strain LFM046, a Producer of Medium
      Chain-Length Polyhydroxyalkanoate.
AB  - Pseudomonas sp. LFM046 is a medium-chain-length polyhydroxyalkanoate (PHAMCL)
      producer capable of using various carbon sources (carbohydrates, organic acids,
      and vegetable oils) and was first isolated from sugarcane cultivation soil in
      Brazil. The genome sequence was found to be 5.97 Mb long with a G+C content of
      66%. 

PMID- 26294617
TI  - Draft Genome Sequence of Veillonella tobetsuensis ATCC BAA-2400T Isolated from
      Human Tongue Biofilm.
AB  - Here, we report the draft genome sequence of Veillonella tobetsuensis ATCC-BAA
      2400(T). This bacterium has the remarkable ability to form oral biofilms. The
      genome is predicted to encode the necessary enzymes involved in the pathway that
      facilitates the conversion of lactate to propionate. 

PMID- 26294618
TI  - Complete Genome Sequences of the Three African Horse Sickness Virus Strains from
      a Commercial Trivalent Live Attenuated Vaccine.
AB  - This is a report of the complete genome sequences of plaque-selected isolates of
      each of the three virus strains included in a South African commercial trivalent
      African horse sickness attenuated live virus vaccine. 

PMID- 26294619
TI  - Draft Genome Sequence of Brevibacillus brevis DZQ7, a Plant Growth-Promoting
      Rhizobacterium with Broad-Spectrum Antimicrobial Activity.
AB  - Brevibacillus brevis DZQ7 is a plant growth-promoting rhizobacterium (PGPR)
      isolated from tobacco rhizosphere. Here, we report the draft genome sequence of
      B. brevis DZQ7. Several functional genes related to antimicrobial activity were
      identified in the genome. 

PMID- 26294620
TI  - Complete Genome Sequence of Classical Swine Fever Virus Strain JSZL, Belonging to
      a New Subgenotype, 2.1d, Isolated in China in 2014.
AB  - The complete genome sequence of classic swine fever virus (CSFV) strain JSZL was
      determined in this study. JSZL was originally isolated from an immune pig farm in
      Jiangsu Province, China. JSZL is more closely related to subgenotype 2.1b than to
      2.1a and 2.1c. Importantly, JSZL was classified into a new subgenotype, 2.1d. 

PMID- 26294621
TI  - Complete Genome Sequence of the Novel Temperate Clostridium difficile Phage
      phiCDIF1296T.
AB  - Clostridium difficile contains many integrated and extrachromosomal genetic
      elements. In this study, we determined, annotated, and analyzed the complete
      genome of the C. difficile bacteriophage phiCDIF1296T using single-molecule real
      time sequencing technology. To our knowledge, this represents the largest genome
      (131 kb) of a temperate C. difficile phage recognized so far. 

PMID- 26294622
TI  - Characterization of Novel HIV-1 Intersubtype CRF01_AE/C and A1/C Recombinants
      from India.
AB  - We report here three novel HIV-1 intersubtype recombinants from India. One among
      those is a recombinant between subtype C and CRF01_AE and another two between A1
      and C. A recombinant virus with CRF01_AE is reported for the first time from
      India. 

PMID- 26294623
TI  - Draft Genome Sequence of Bacillus cytotoxicus CVUAS 2833, a Very Close Relative
      to Type Strain NVH 391-98 Isolated from a Different Location.
AB  - We report the draft genome sequence of Bacillus cytotoxicus CVUAS 2833, isolated
      from potato puree in Germany (2007), which is-despite its clearly different
      source-very similar to the type strain B. cytotoxicus NVH 391-98 isolated in
      France (average nucleotide identity, 99.5%). 

PMID- 26294624
TI  - Complete Genome Sequence of a Bell Pepper Endornavirus Isolate from Canada.
AB  - Bell pepper endornavirus (BPEV) is a double-stranded RNA virus infecting
      economically important crops, such as peppers. Next-generation sequencing of
      small RNAs extracted from the leaves of a pepper plant showing mild viral
      symptoms, along with subsequent analysis, identified BPEV. The complete genome of
      this isolate was cloned and sequenced. 

PMID- 26294625
TI  - Draft Genome Sequence of Antarctic Pseudomonas sp. Strain KG01 with Full
      Potential for Biotechnological Applications.
AB  - We report here the draft genome sequence of a free-living psychrotolerant,
      Pseudomonas sp. strain KG01, isolated from an Antarctic soil sample and
      displaying interesting antimicrobial and surfactant activities. The sequence is
      6.3 Mb long and includes 5,648 predicted-coding sequences. 

PMID- 26294626
TI  - Draft Genome Sequence of a Community-Associated Methicillin-Resistant Panton
      Valentine Leukocidin-Positive Staphylococcus aureus Sequence Type 30 Isolate from
      a Pediatric Patient with a Lung Infection in Brazil.
AB  - The sequence of methicillin-resistant Staphylococcus aureus strain B6 (sequence
      type 30 [ST30], spa type t433, staphylococcal chromosomal cassette mec element
      [SCCmec] type IVc, Panton-Valentine leukocidin [PVL] positive), isolated from a
      pediatric patient with a lung infection in Niteroi, Rio de Janeiro, Brazil, is
      described here. The draft genome sequence includes a 2.8-Mb chromosome,
      accompanied by a 20-kb plasmid containing blaZ and two small cryptic plasmids. 

PMID- 26294627
TI  - Draft Genome Sequences of 19 Salmonella enterica Serovar Typhimurium [4,5:i:-]
      Strains Resistant to Nalidixic Acid from a Long-Term Outbreak in Italy.
AB  - Here, we present the draft genome sequences of 19 Salmonella enterica serovar
      Typhimurium monophasic variant [4,5:i:-] strains involved in a long-term
      salmonellosis outbreak that occurred in central Italy in 2013 to 2014. 

PMID- 26294628
TI  - Draft Genome Sequence of a Staphylococcus aureus Strain Isolated from a Cow with
      Clinical Mastitis.
AB  - We report here the draft genome of Staphylococcus aureus causing clinical
      mastitis in a cow from India. It is a major causative agent of mastitis and,
      further, livestock-associated strains are emerging as a potential threat to
      public health, thereby warranting studies to understand the genome of this deadly
      pathogen. 

PMID- 26294629
TI  - Genome Sequence of a Burkholderia pseudomallei Clinical Isolate from a Patient
      with Community-Acquired Pneumonia and Septicemia.
AB  - Here, we report the draft genome sequence of Burkholderia pseudomallei
      CM_Manipal, the causative agent of melioidosis isolated from a diabetic patient
      in Manipal, southern India. The draft genome consists of 107 contigs and is
      7,209,157 bp long. A total of 5,600 coding sequences (CDSs), 60 tRNAs, 12 rRNAs,
      and one noncoding RNA (ncRNA) were predicted from this assembly. 

PMID- 26294630
TI  - Complete Genome Sequence of Acinetobacter baumannii Strain B8342, a Motility
      Positive Clinical Isolate.
AB  - Acinetobacter baumannii is an emerging Gram-negative pathogen responsible for
      health care-associated infections. In this study, we determined the genome of a
      motility-positive clinical strain, B8342, isolated from a hospital in southern
      India. The B8342 genome, which is 3.94 Mbp, was generated by de novo assembly of
      PacBio long-read sequencing data. 

PMID- 26294631
TI  - First Complete Genome Sequence of Pseudomonas aeruginosa (Schroeter 1872) Migula
      1900 (DSM 50071T), Determined Using PacBio Single-Molecule Real-Time Technology.
AB  - The first complete genome sequence of the type strain Pseudomonas aeruginosa
      (Schroeter 1872) Migula 1900 (DSM 50071(T)) was determined in a single contig by
      PacBio RS II. The genome (6,317,050 bp, G+C content of 66.52%) contained 10 sets
      of >1,000-bp identical sequence pairs and 183 tandem repeats. 

PMID- 26294632
TI  - Draft Genome Sequence of the Phenol-Degrading Bacterium Pseudomonas putida H.
AB  - In this study, we report the draft genome of Pseudomonas putida H, a well-known
      bacterium capable of degrading various aromatic compounds. Its genome size is
      6,065 Mbp with a GC content of 61.6%. This work will aid future studies on this
      versatile bacterium. 

PMID- 26294633
TI  - Draft Genome Sequence of Parabacteroides goldsteinii with Putative Novel Metallo
      beta-Lactamases Isolated from a Blood Culture from a Human Patient.
AB  - Parabacteroides goldsteinii was isolated from a blood culture. Genomic DNA was
      sequenced using a MiSeq sequencer and assembled using the SPAdes genome
      assembler. The draft genome sequence was 6,851,868 bp, spanning 282 contigs of
      5,253 coding sequences, 66 tRNAs, and 5 rRNAs. Several putative novel metallo
      beta-lactamases were discovered. 

PMID- 26294635
TI  - Complete Genome Sequence of Achromobacter xylosoxidans MN001, a Cystic Fibrosis
      Airway Isolate.
AB  - The genome of Achromobacter xylosoxidans MN001, a strain isolated from sputum
      derived from an adult cystic fibrosis patient, was sequenced using combined
      single-molecule real-time and Illumina sequencing. Assembly of the complete
      genome resulted in a 5,876,039-bp chromosome, representing the smallest A.
      xylosoxidans genome sequenced to date. 

PMID- 26294634
TI  - Complete Genome Sequence of the Nonpathogenic Soil-Dwelling Bacterium Clostridium
      sporogenes Strain NCIMB 10696.
AB  - Clostridium sporogenes is a harmless spore-forming anaerobe that is widely
      distributed in soil/water and in the intestines of humans and animals. It is
      extensively used as a safe model to test the suitability of new preservative
      methods by the food industry and has potential to deliver therapeutic agents to
      tumors. 

PMID- 26294636
TI  - Complete Genome Sequence of a Foot-and-Mouth Disease Virus of Serotype A Isolated
      from Vietnam in 2013.
AB  - The complete genome sequence of a foot-and-mouth disease virus (FMDV) found in an
      isolate collected in northern Vietnam in 2013 appears to be closely related to a
      genetic cluster formed with isolates from China, Mongolia, and Russia in 2013.
      All of these are classified to fall within the Sea-97 lineage, for which little
      complete genome data are available. 

PMID- 26294637
TI  - Genome Sequence of Devriesea agamarum, Isolated from Agamid Lizards with
      Dermatitis.
AB  - We report the genome sequence of Devriesea agamarum strain IMP2, isolated from
      the liver of a female Agama impalearis. This actinobacterium is associated with
      septicemia and dermatitis in agamid lizards. Availability of this genome sequence
      will contribute to the understanding of this pathogen's virulence. 

PMID- 26294638
TI  - Complete Genome Sequence of Prevotella intermedia Strain 17-2.
AB  - Prevotella intermedia, a Gram-negative black-pigmented anaerobic rod, is
      frequently isolated from not only periodontal pockets but also purulent
      infections. We report here the complete genome sequence of P. intermedia strain
      17-2, which is a non-exopolysaccharide-producing variant obtained from
      exopolysaccharide (EPS)-producing P. intermedia strain 17 stock culture. 

PMID- 26294639
TI  - Draft Genome Sequence of a Bacillus Bacterium from the Atacama Desert Wetlands
      Metagenome.
AB  - We report here the draft genome sequence of a Bacillus bacterium isolated from
      the microflora of Nostoc colonies grown at the Andean wetlands in northern Chile.
      We consider this genome sequence to be a molecular tool for exploring microbial
      relationships and adaptation strategies to the prevailing extreme conditions at
      the Atacama Desert. 

PMID- 26294640
TI  - Complete Genome Sequence of Acinetobacter baumannii Strain B8300, Which Displays
      High Twitching Motility.
AB  - Acinetobacter baumannii has emerged as an important nosocomial pathogen causing
      health care-associated infections. In this study, we determined the genome of a
      twitching-positive clinical strain, B8300, isolated from a hospital in southern
      India. De novo assembly of PacBio long-read sequencing data generated the B8300
      genome that consists of a chromosome of 3.82 Mbp and a plasmid of 25.15 kbp. 

PMID- 26294641
TI  - Complete Genome Sequence of the Type Strain Corynebacterium epidermidicanis DSM
      45586, Isolated from the Skin of a Dog Suffering from Pruritus.
AB  - The complete genome sequence of Corynebacterium epidermidicanis DSM 45586
      comprises 2,692,072 bp with 58.06% G+C content. The annotation revealed 2,466
      protein-coding regions, including genes for surface-anchored proteins with Cna B
      type or bacterial Ig-like domains and for an adhesive SpaABC-type pilus with
      similarity to fimbrial subunits of Corynebacterium resistens DSM 45100. 

PMID- 26294642
TI  - Seizure Frequency Can Alter Brain Connectivity: Evidence from Resting-State fMRI.
AB  - BACKGROUND AND PURPOSE: The frequency of seizures is an important factor that can
      alter functional brain connectivity. Analysis of this factor in patients with
      epilepsy is complex because of disease- and medication-induced confounders.
      Because patients with hot-water epilepsy generally are not on long-term drug
      therapy, we used seed-based connectivity analysis in these patients to assess
      connectivity changes associated with seizure frequency without confounding from
      antiepileptic drugs. MATERIALS AND METHODS: Resting-state fMRI data from 36
      patients with hot-water epilepsy (18 with frequent seizures [>2 per month] and 18
      with infrequent seizures [<=2 per month]) and 18 healthy age- and sex-matched
      controls were analyzed for seed-to-voxel connectivity by using 106 seeds. Voxel
      wise paired t-test analysis (P < .005, corrected for false-discovery rate) was
      used to identify significant intergroup differences between these groups.
      RESULTS: Connectivity analysis revealed significant differences between the 2
      groups (P < .001). Patients in the frequent-seizure group had increased
      connectivity within the medial temporal structures and widespread areas of poor
      connectivity, even involving the default mode network, in comparison with those
      in the infrequent-seizure group. Patients in the infrequent-seizure group had
      focal abnormalities with increased default mode network connectivity and
      decreased left entorhinal cortex connectivity. CONCLUSIONS: The results of this
      study suggest that seizure frequency can alter functional brain connectivity,
      which can be visualized by using resting-state fMRI. Imaging features such as
      diffuse network abnormalities, involvement of the default mode network, and
      recruitment of medial temporal lobe structures were seen only in patients with
      frequent seizures. Future studies in more common epilepsy groups, however, will
      be required to further establish this finding.

PMID- 26294643
TI  - Therapeutic Internal Carotid Artery Occlusion for Large and Giant Aneurysms: A
      Single Center Cohort of 146 Patients.
AB  - BACKGROUND AND PURPOSE: At our institution, patients with large or giant ICA
      aneurysms are preferably treated with endovascular ICA balloon occlusion.
      Alternative treatment or conservative treatment is offered only for patients who
      cannot tolerate permanent ICA occlusion. In this observational study, we report
      the clinical and imaging results of ICA occlusion for aneurysms in a large single
      center patient cohort. MATERIALS AND METHODS: Between January 1995 and January
      2015, occlusion of the ICA was considered in 146 patients with large or giant ICA
      aneurysms. Ninety-six patients (66%) passed the angiographic test occlusion, and,
      in 88 of these 96 patients (92%), the ICA was permanently occluded. In 11 of 88
      patients with angiographic tolerance, ICA occlusion was performed with the
      patient under general anesthesia without clinical testing. RESULTS: There was 1
      hypoperfusion infarction after hypovolemic shock from a large retroperitoneal
      hematoma (complication rate 1.1% [95% CI, 1%-6.8%]). The mean imaging and
      clinical follow-up was 35 months (median 18 months; range, 3-180 months). On the
      latest MR imaging, 87 of 88 aneurysms (99%) were completely occluded and 61 of 80
      aneurysms (76%) were decreased in size or completely obliterated. Of 62 patients
      who presented with cranial nerve dysfunction by mass effect of the aneurysm, 30
      (48%) were cured, 25 (40%) improved, 6 (10%) were unchanged, and 1 patient (2%)
      was hemiplegic after a complication. CONCLUSIONS: ICA occlusion for large and
      giant aneurysms after angiographic test occlusion was safe and effective. Two
      thirds of eligible patients passed the angiographic test. Most aneurysms shrunk,
      and most cranial nerve dysfunctions were cured or improved.

PMID- 26294644
TI  - Mechanical Thrombectomy Using the New ERIC Retrieval Device Is Feasible,
      Efficient, and Safe in Acute Ischemic Stroke: A Swiss Stroke Center Experience.
AB  - BACKGROUND AND PURPOSE: Intravenous thrombolysis and mechanical thrombectomy
      predominantly using stent retrievers have been shown to effectively restore
      cerebral blood flow and improve functional outcome in patients with acute
      ischemic stroke. We sought to determine the safety and feasibility of mechanical
      thrombectomy using the new ERIC retrieval device. MATERIALS AND METHODS: We
      identified 36 consecutive patients from our Stroke Center registry with acute
      ischemic stroke who were treated with the new ERIC retriever from September 2013
      to December 2014. Patients with ischemic stroke meeting the following criteria
      were eligible: onset-to-treatment time of <=4.5 hours or wake-up stroke (n = 10)
      with relevant CT perfusion mismatch, NIHSS score of >=4, and proof of large
      vessel occlusion in the anterior circulation on CT angiography. We assessed the
      baseline characteristics including age, sex, comorbidities, stroke severity, site
      of vessel occlusion, presence of tissue at risk, and treatment-related parameters
      such as onset-to-treatment time, recanalization grade, and outcome. RESULTS: The
      mean age was 70 +/- 13 years, and the median NIHSS score on admission was 18
      (interquartile range, 10-20). Seventeen of 36 patients were on platelet
      inhibitors or anticoagulants before endovascular treatment (47.2%); 20 patients
      received intravenous thrombolysis (55.5%). The ERIC was used as the sole
      retriever in 28 patients (77.8%) and as a rescue device in 8. Excellent
      recanalization was achieved in 30/36 patients (83.3%) with TICI 3 in 19/36 and 2b
      in 11/36, respectively. Median procedural time in these patients was 90 minutes
      (interquartile range, 58-133 minutes). No intraprocedural complications occurred.
      CONCLUSIONS: In this observational study, the new ERIC retrieval device was
      technically feasible, safe, and effective in acute ischemic stroke with large
      vessel occlusion.

PMID- 26294645
TI  - One-Year Angiographic Follow-Up after WEB-SL Endovascular Treatment of Wide-Neck
      Bifurcation Intracranial Aneurysms.
AB  - BACKGROUND AND PURPOSE: Endovascular coiling of wide-neck intracranial aneurysms
      is associated with low rates of initial angiographic occlusion and high rates of
      recurrence. The WEB intrasaccular device has been developed specifically for this
      indication. To date, there has been no report of the long-term follow-up of a
      series of patients with aneurysms treated with this type of device, to our
      knowledge. Our aim was to evaluate a 1-year follow-up of angiographic results in
      a prospective single-center series of patients treated with the WEB-Single-Layer
      (SL) device. MATERIALS AND METHODS: All patients treated with the WEB-SL device
      in our center between August 2013 and May 2014 were prospectively included. One
      year angiographic outcomes were assessed. Results at follow-up were graded as
      complete occlusion, neck remnant, or residual aneurysm. RESULTS: Eight patients
      with 8 unruptured wide-neck aneurysms were enrolled in this study. Average dome
      width was 7.5 mm (range, 5.4-10.7 mm), and average neck size was 4.9 mm (range,
      2.6-6.5 mm). One-year angiographic follow-up obtained in all aneurysms included 1
      complete aneurysm occlusion (12.5%), 6 neck remnants (75%), and 1 aneurysm
      remnant (12.5%). Of 8 aneurysms, worsening of aneurysm occlusion was observed in
      2 (25%) by compression of the WEB device. There was no angiographic recurrence of
      initially totally occluded aneurysms. No bleeding was observed during the follow
      up period. CONCLUSIONS: Endovascular therapy of intracranial aneurysms with the
      WEB-SL device allows treatment of wide-neck aneurysms with a high rate of neck
      remnant at 1 year, at least partially explained by WEB compression. Initial size
      selection and technologic improvements could be an option for optimization of
      aneurysm occlusion in WEB-SL treatment.

PMID- 26294646
TI  - Nigrosome 1 Detection at 3T MRI for the Diagnosis of Early-Stage Idiopathic
      Parkinson Disease: Assessment of Diagnostic Accuracy and Agreement on Imaging
      Asymmetry and Clinical Laterality.
AB  - BACKGROUND AND PURPOSE: In the early stages of idiopathic Parkinson disease,
      motor symptoms are usually asymmetric. We aimed to assess the feasibility of
      nigrosome 1 detection at 3T MR imaging to analyze the agreement of its asymmetry
      and clinical laterality. MATERIALS AND METHODS: High-resolution 3D multiecho
      imaging was performed at 3T MR imaging in 13 healthy subjects and 24 patients
      with idiopathic Parkinson disease confirmed by N-3-fluoropropyl-2-beta
      carbomethoxy-3-beta-(4-iodophenyl) nortropane ((18)F-FP-CIT) PET. The nigrosome 1
      detection findings by using the MR imaging data were rated as "normal," "possibly
      abnormal," and "abnormal" by 2 independent reviewers. The degree of (18)F-FP-CIT
      binding was visually assessed in the caudate nucleus and putamen on PET images.
      Clinical laterality was evaluated by scores of the Unified Parkinson Disease
      Rating Scale, Part III. Asymmetry of the affected nigrosome 1 and the degree of
      (18)F-FP-CIT binding were analyzed for agreement with clinical laterality.
      RESULTS: The diagnostic sensitivity, specificity, and accuracy of the nigrosome 1
      detection at 3T MR imaging was 100%, 84.6%, and 94.6%, respectively. Interrater
      agreements for the abnormality and asymmetry of nigrosome 1 were excellent (kappa
      = 0.863 and 0.835, respectively). In patients with idiopathic Parkinson disease,
      the agreement of asymmetry between clinical laterality and nigrosome 1 detection
      was good (kappa = 0.724). The degree of the (18)F-FP-CIT PET binding showed fair
      agreement (kappa = 0.235) with clinical laterality. CONCLUSIONS: The abnormality
      involving nigrosome 1 can be detected at 3T MR imaging with an accuracy of 94.6%.
      The clinical laterality is in high concordance with the laterality of the
      nigrosome 1 detection at 3T (kappa = 0.724).

PMID- 26294647
TI  - Fusion of Freehand SPECT and Ultrasound to Perform Ultrasound-Guided Fine-Needle
      Aspiration Cytology of Sentinel Nodes in Head and Neck Cancer.
AB  - BACKGROUND AND PURPOSE: Criteria for ultrasound-guided fine-needle aspiration
      cytology (USgFNAC) for the detection of occult lymph node metastasis in patients
      with clinically negative head and neck cancer are based on the morphology of
      cervical lymph nodes. To improve the selection of lymph nodes for USgFNAC, we
      examined the feasibility of fused freehand single-photon emission tomography
      ultrasound-guided fine-needle cytology (freehand SPECT-USgFNAC) of sentinel nodes
      in patients with early stage oral and head and neck skin cancer. MATERIALS AND
      METHODS: Six patients with early-stage head and neck cancer (4 oral and 2 head
      and neck skin cancers) and a clinically negative neck who were scheduled for
      transoral or local excision and a sentinel node procedure underwent USgFNAC and
      freehand SPECT-USgFNAC preoperatively. RESULTS: All freehand SPECT sonographic
      examinations were technically successful in terms of identifying sentinel nodes.
      All aspirates of sentinel nodes obtained by freehand SPECT-USgFNAC contained
      substantial radioactivity, confirming puncture of the sentinel nodes. USgFNAC
      evaluated 13 lymph nodes; freehand SPECT-USgFNAC, 19 nodes; and sentinel node
      biopsy, 13 nodes. Three sentinel nodes were histopathologically positive and were
      selected for aspiration cytology by freehand SPECT-USgFNAC, but not by
      conventional ultrasound. The cytologic examination findings of the aspirations
      were negative or inconclusive. CONCLUSIONS: Freehand SPECT ultrasound can
      identify sentinel nodes and could potentially improve USgFNAC in patients with
      head and neck cancer by better selection of lymph nodes at highest risk of having
      metastases (sentinel nodes), but its sensitivity is limited by sampling error and
      insufficient aspirated material for cytology.

PMID- 26294648
TI  - 3D Printing of Intracranial Aneurysms Using Fused Deposition Modeling Offers
      Highly Accurate Replications.
AB  - BACKGROUND AND PURPOSE: As part of a multicenter cooperation (Aneurysm-Like
      Synthetic bodies for Testing Endovascular devices in 3D Reality) with focus on
      implementation of additive manufacturing in neuroradiologic practice, we
      systematically assessed the technical feasibility and accuracy of several
      additive manufacturing techniques. We evaluated the method of fused deposition
      modeling for the production of aneurysm models replicating patient-specific
      anatomy. MATERIALS AND METHODS: 3D rotational angiographic data from 10 aneurysms
      were processed to obtain volumetric models suitable for fused deposition
      modeling. A hollow aneurysm model with connectors for silicone tubes was
      fabricated by using acrylonitrile butadiene styrene. Support material was
      dissolved, and surfaces were finished by using NanoSeal. The resulting models
      were filled with iodinated contrast media. 3D rotational angiography of the
      models was acquired, and aneurysm geometry was compared with the original patient
      data. RESULTS: Reproduction of hollow aneurysm models was technically feasible in
      8 of 10 cases, with aneurysm sizes ranging from 41 to 2928 mm(3) (aneurysm
      diameter, 3-19 mm). A high level of anatomic accuracy was observed, with a mean
      Dice index of 93.6% +/- 2.4%. Obstructions were encountered in vessel segments of
      <1 mm. CONCLUSIONS: Fused deposition modeling is a promising technique, which
      allows rapid and precise replication of cerebral aneurysms. The porosity of the
      models can be overcome by surface finishing. Models produced with fused
      deposition modeling may serve as educational and research tools and could be used
      to individualize treatment planning.

PMID- 26294650
TI  - Foreign Body Emboli following Cerebrovascular Interventions: Clinical,
      Radiographic, and Histopathologic Features.
AB  - Foreign material emboli following cerebral, cardiac, and peripheral
      catheterizations have been reported since the mid-1990s. Catheter coatings have
      been frequently implicated. The most recent surge of interest in this phenomenon
      within the neurointerventional community is associated with procedures using flow
      diversion devices for the treatment of cerebral aneurysms. Following coil
      supported Pipeline embolization in 4 cases and stent-supported coiling in 1, 5
      patients developed multiple subcentimeter enhancing lesions, usually with
      surrounding edema and variable magnetic susceptibility in the vascular
      territories of the treated aneurysms. Conventional angiography findings were
      unrevealing. Laboratory work-up showed mild CSF protein elevation with no
      leukocytosis. Brain biopsy in 2 cases revealed granulomatous angiitis encasing
      foreign material, identical in stain appearance to a polyvinylpyrrolidone
      catheter coating. Corticosteroid administration typically produced clinical
      improvement. A heterogeneous radiographic and clinical course was noted, with
      rise and fall in the number of enhancing lesions in 2 patients and persistence in
      others. The etiology may be related to widespread adoption of increasingly
      sophisticated catheterization techniques.

PMID- 26294649
TI  - Hyperintense Dentate Nuclei on T1-Weighted MRI: Relation to Repeat Gadolinium
      Administration.
AB  - BACKGROUND AND PURPOSE: A hyperintense appearance of the dentate nucleus on T1
      weighted MR images has been related to various clinical conditions, but the
      etiology remains indeterminate. We aimed to investigate the possible associations
      between a hyperintense appearance of the dentate nucleus on T1-weighted MR images
      in patients exposed to radiation and factors including, but not limited to, the
      cumulative number of contrast-enhanced MR images, amount of gadolinium
      administration, dosage of ionizing radiation, and patient demographics. MATERIALS
      AND METHODS: The medical records of 706 consecutive patients who were treated
      with brain irradiation at The Johns Hopkins Medical Institutions between 1995 and
      2010 were blindly reviewed by 2 readers. RESULTS: One hundred eighty-four
      subjects were included for dentate nuclei analysis. Among the 184 subjects who
      cumulatively underwent 2677 MR imaging studies following intravenous gadolinium
      administration, 103 patients had hyperintense dentate nuclei on precontrast T1
      weighted MR images. The average number of gadolinium-enhanced MR imaging studies
      performed in the group with normal dentate nuclei was significantly lower than
      that of the group with hyperintense dentate nuclei. The average follow-up time
      was 62.5 months. No significant difference was observed between hyperintense and
      normal dentate nuclei groups in terms of exposed radiation dose, serum creatinine
      and calcium/phosphate levels, patient demographics, history of chemotherapy, and
      strength of the scanner. No dentate nuclei abnormalities were found on the
      corresponding CT scans of patients with hyperintense dentate nuclei (n = 44). No
      dentate nuclei abnormalities were found in 53 healthy volunteers. CONCLUSIONS:
      Repeat performance of gadolinium-enhanced studies likely contributes to a long
      standing hyperintense appearance of dentate nuclei on precontrast T1-weighted-MR
      images.

PMID- 26294651
TI  - Whole-Brain N-Acetylaspartate Concentration Is Preserved during Mild Hypercapnia
      Challenge.
AB  - BACKGROUND AND PURPOSE: Although NAA is often used as a marker of neuronal health
      and integrity in neurologic disorders, its normal response to physiologic
      challenge is not well-established and its changes are almost always attributed
      exclusively to brain pathology. The purpose of this study was to test the
      hypothesis that the neuronal cell marker NAA, often used to assess neuronal
      health and integrity in neurologic disorders, is not confounded by (possibly
      transient) physiologic changes. Therefore, its decline, when observed by using
      (1)H-MR spectroscopy, can almost always be attributed exclusively to brain
      pathology. MATERIALS AND METHODS: Twelve healthy young male adults underwent a
      transient hypercapnia challenge (breathing 5% CO2 air mixture), a potent
      vasodilator known to cause a substantial increase in CBF and venous oxygenation.
      We evaluated their whole-brain NAA by using nonlocalizing proton MR spectroscopy,
      venous oxygenation with T2-relaxation under spin-tagging MR imaging, CBF with
      pseudocontinuous arterial spin-labeling, and the cerebral metabolic rate of
      oxygen, during normocapnia (breathing room air) and hypercapnia. RESULTS: There
      was insignificant whole-brain NAA change (P = .88) from normocapnia to
      hypercapnia and back to normocapnia in this cohort, as opposed to highly
      significant increases: 28.0 +/- 10.3% in venous oxygenation and 49.7 +/- 16.6% in
      global CBF (P < 10(-4)); and a 6.4 +/- 10.9% decrease in the global cerebral
      metabolic rate of oxygen (P = .04). CONCLUSIONS: Stable whole-brain NAA during
      normocapnia and hypercapnia, despite significant global CBF and cerebral
      metabolic rate of oxygen changes, supports the hypothesis that global NAA changes
      are insensitive to transient physiology. Therefore, when observed, they most
      likely reflect underlying pathology resulting from neuronal cell
      integrity/viability changes, instead of a response to physiologic changes.

PMID- 26294652
TI  - Emergency Stenting of the Extracranial Internal Carotid Artery in Combination
      with Anterior Circulation Thrombectomy in Acute Ischemic Stroke: A Retrospective
      Multicenter Study.
AB  - BACKGROUND AND PURPOSE: Several small case series reported a favorable clinical
      outcome for emergency stent placement in the extracranial internal carotid artery
      combined with mechanical thrombectomy in acute stroke. The rate of
      postinterventional symptomatic intracranial hemorrhages was reported to be as
      high as 20%. Therefore, we investigated the safety and efficacy of this technique
      in a large multicentric cohort. MATERIALS AND METHODS: The data bases of 4 German
      stroke centers were screened for all patients who received emergency stent
      placement of the extracranial internal carotid artery in combination with
      mechanical thrombectomy of the anterior circulation between 2007 and 2014. The
      primary outcome measure was the rate of symptomatic intracranial hemorrhage
      according to the European Cooperative Acute Stroke Study III criteria; secondary
      outcome measures included the angiographic revascularization results and clinical
      outcome. RESULTS: One hundred seventy patients with a median age of 64 years
      (range, 25-88 years) were treated. They presented after a median of 98 minutes
      (range, 52-160 minutes) with a median NIHSS score of 15 (range, 12-19).
      Symptomatic intracranial hemorrhages occurred in 15/170 (9%) patients; there was
      no statistically significant difference among groups pertaining to age, sex,
      intravenous rtPA, procedural timings, and the rate of successful recanalization.
      In 130/170 (77%) patients, a TICI score of >= 2b could be achieved. The in
      hospital mortality rate was 19%, and 36% of patients had a favorable outcome at
      follow-up. CONCLUSIONS: Emergency stent placement in the extracranial internal
      carotid artery in combination with anterior circulation thrombectomy is effective
      and safe. It is not associated with a significantly higher risk of symptomatic
      intracranial hemorrhage compared with published series for mechanical
      thrombectomy alone.

PMID- 26294653
TI  - Independent Poor Prognostic Factors for True Progression after Radiation Therapy
      and Concomitant Temozolomide in Patients with Glioblastoma: Subependymal
      Enhancement and Low ADC Value.
AB  - BACKGROUND AND PURPOSE: Subependymal enhancement and DWI have been reported to be
      useful MR imaging markers for identifying true progression. Our aim was to
      determine whether the subependymal enhancement pattern and ADC can differentiate
      true progression from pseudoprogression in patients with glioblastoma multiforme
      treated with concurrent chemoradiotherapy by using temozolomide. MATERIALS AND
      METHODS: Forty-two patients with glioblastoma multiforme with newly developed or
      enlarged enhancing lesions on the first follow-up MR images obtained within 2
      months of concurrent chemoradiotherapy completion were included. Subependymal
      enhancement was analyzed for the presence, location, and pattern (local or
      distant relative to enhancing lesions). The mean ADC value and the fifth
      percentile of the cumulative ADC histogram were determined. A multiple logistic
      regression analysis was performed to identify independent factors associated with
      true progression. RESULTS: Distant subependymal enhancement (ie, extending >1 cm
      or isolated from the enhancing lesion) was significantly more common in true
      progression (n = 24) than in pseudoprogression (n = 18) (P = .042). The fifth
      percentile of the cumulative ADC histogram was significantly lower in true
      progression than in pseudoprogression (P = .014). Both the distant subependymal
      enhancement and the fifth percentile of the cumulative ADC histogram were
      independent factors associated with true progression (P = .041 and P = .033,
      respectively). Sensitivity and specificity for the diagnosis of true progression
      were 83% and 67%, respectively, by using both factors. CONCLUSIONS: Both the
      distant subependymal enhancement and the fifth percentile of the cumulative ADC
      histogram were significant independent factors predictive of true progression.

PMID- 26294654
TI  - A Feasibility Study of Tumor Motion Estimate With Regional Deformable
      Registration Method for 4-Dimensional Radiation Therapy of Lung Cancer.
AB  - This study aims to employ 4-dimensional computed tomography to quantify
      intrafractional tumor motion for patients with lung cancer to improve target
      localization in radiation therapy. A multistage regional deformable registration
      was implemented to calculate the excursion of gross tumor volume (GTV) during a
      breathing cycle. GTV was initially delineated on 0% phase of 4-dimensional
      computed tomography manually, and a subregion with 20 mm margin supplemented to
      GTV was generated with Eclipse treatment planning system (Varian Medical Systems,
      Palo Alto, California). The structures, together with the 4-dimensional computed
      tomography set, were exported into an in-house software, with which a 3-stage B
      spline deformable registration was carried out to map the subregion and warp GTV
      contour to other breathing phases. The center of mass of the GTV was computed
      using the contours, and the tumor motion was appraised as the excursion of the
      center of mass between 0% phase and other phases. Application of the algorithm to
      the 10 patients showed that clinically satisfactory outcomes were achievable with
      a spatial accuracy around 2 mm for GTV contour propagation between adjacent
      phases and 3 mm between opposite phases. The tumor excursion was determined in
      the vast range of 1 mm through 1.6 cm, depending on the tumor location and tumor
      size. Compared to the traditional whole image-based registration, the regional
      method was found computationally a factor of 5 more efficient. The proposed
      technique has demonstrated its capability in extracting thoracic tumor motion and
      should find its application in 4-dimensional radiation therapy in the future to
      maximally utilize the available spatial-temporal information.

PMID- 26294655
TI  - Effect of shRNA-Mediated Gene Silencing of Bmi-1 Expression on Chemosensitivity
      of CD44+ Nasopharyngeal Carcinoma Cancer Stem-Like Cells.
AB  - In this study, we investigate the effect of short hairpin RNA-mediated gene
      silencing of Bmi-1 expression on chemosensitivity of CD44(+) nasopharyngeal
      carcinoma cancer stem-like cells. The sequence-specific short hairpin RNA
      lentivirus targeting at human Bmi-1 was synthesized and used to infect CD44(+)
      nasopharyngeal cells that were sorted by flow cytometry. We also employed flow
      cytometry to detect transfection efficiency. Real-time polymerase chain reaction
      was used to detect Bmi-1 and its downstream repressor genes p16(INK4a) and
      p14(ARF) messenger RNA, while each protein expression level of Bmi-1, p16(INK4a),
      p14(ARF), and p53 was confirmed by Western blotting protocol. Tumor spheroid
      assay was used to evaluate the self-renewal capacity. 3-(4,5-dimethylthiazol-2
      yl)-2, 5-diphenyltetrazolium bromide assay and colony formation assay were
      applied to detect proliferation capacity and colony-forming capacity under
      different concentrations of chemotherapeutic drugs 5-fluorouracil or cisplatin.
      Transwell cell migration and invasion assay were employed to observe migration
      and invasion capacity after cells were exposed to cisplatin for 24 hours. The
      constructed short hairpin RNA lentivirus targeting Bmi-1 gene successfully
      infected into the CD44(+) nasopharyngeal carcinoma cells and effectively
      inhibited the Bmi-1 messenger RNA and protein expression level, while the
      expression level of Bim-1 target genes, p16(INK4a), p14(ARF), and p53 was
      significantly increased (P < .05). Notably, the proliferation, colony formation,
      migration, and invasion capabilities of the sequence-specific short hairpin RNA
      lentivirus-infected CD44(+) nasopharyngeal carcinoma cells reduced significantly
      under chemotherapeutic treatments (P < .05). Our results indicated that Bmi-1 may
      play an important role in the chemosensitivity of CD44(+) nasopharyngeal
      carcinoma cancer stem-like cells. Bmi-1 may be a potential new target for the
      treatment of nasopharyngeal carcinoma displaying chemotherapy resistance.

PMID- 26294656
TI  - Platelets Play Differential Role During the Initiation and Progression of
      Autoimmune Neuroinflammation.
AB  - RATIONALE: Platelets are known to participate in vascular pathologies; however,
      their role in neuroinflammatory diseases, such as multiple sclerosis (MS), is
      unknown. Autoimmune CD4 T cells have been the main focus of studies of MS,
      although the factors that regulate T-cell differentiation toward pathogenic T
      helper-1/T helper-17 phenotypes are not completely understood. OBJECTIVE: We
      investigated the role of platelets in the modulation of CD4 T-cell functions in
      patients with MS and in mice with experimental autoimmune encephalitis, an animal
      model for MS. METHODS AND RESULTS: We found that early in MS and experimental
      autoimmune encephalitis, platelets degranulated and produced soluble factors
      serotonin (5-hydroxytryptamine), platelet factor 4, and platelet-activating
      factor, which specifically stimulated differentiation of T cells toward
      pathogenic T helper-1, T helper-17, and interferon-gamma/interleukin-17-producing
      CD4 T cells. At the later stages of MS and experimental autoimmune encephalitis,
      platelets became exhausted in their ability to produce proinflammatory factors
      and stimulate CD4 T cells but substantially increased their ability to form
      aggregates with CD4 T cells. Formation of platelet-CD4 T-cell aggregates involved
      the interaction of CD62P on activated platelets with adhesion molecule CD166 on
      activated CD4 T cells, contributing to downmodulation of CD4 T-cell activation,
      proliferation, and production of interferon-gamma. Blocking of formation of
      platelet-CD4 T-cell aggregates during progression of experimental autoimmune
      encephalitis substantially enhanced proliferation of CD4 T cells in the central
      nervous system and the periphery leading to exacerbation of the disease.
      CONCLUSION: Our study indicates differential roles for platelets in the
      regulation of functions of pathogenic CD4 T cells during initiation and
      progression of central nervous system autoimmune inflammation.

PMID- 26294659
TI  - Handheld Thermoacoustic Scanning System Based on a Linear-array Transducer.
AB  - To receive the information necessary for imaging, traditional microwave-induced
      thermoacoustic imaging systems (MITISs) use a type of circular-scanning mode
      using single or arc detectors. However, the use of MITISs for body scanning is
      complicated by restrictions in space and imaging time. A linear-array detector,
      the most widely used transducer in medical ultrasound imaging systems for body
      scanning, is a possible alternative to MITISs for scanning biological tissues,
      such as from the breast or limbs. In this paper, a handheld MITIS, based on a
      linear-array detector and a multiple data acquisition system, is described, and
      the capacity of the system is explored experimentally. First, the vertical and
      lateral resolution of the system is discussed. Next, real-time imaging of a
      moving object, obtained with an image capture rate of 20 frame/s, is described.
      Finally, a phantom experiment is detailed, investigating the overall imaging
      capability. The results show that this system achieves rapid scanning with a
      large field of view. The system has the obvious advantages of being handheld, not
      using coupled fluids, and achieving real-time imaging with a large field of view,
      which make this MITIS more suitable for clinical applications.

PMID- 26294658
TI  - Mextli proteins use both canonical bipartite and novel tripartite binding modes
      to form eIF4E complexes that display differential sensitivity to 4E-BP
      regulation.
AB  - The eIF4E-binding proteins (4E-BPs) are a diverse class of translation regulators
      that share a canonical eIF4E-binding motif (4E-BM) with eIF4G. Consequently, they
      compete with eIF4G for binding to eIF4E, thereby inhibiting translation
      initiation. Mextli (Mxt) is an unusual 4E-BP that promotes translation by also
      interacting with eIF3. Here we present the crystal structures of the eIF4E
      binding regions of the Drosophila melanogaster (Dm) and Caenorhabditis elegans
      (Ce) Mxt proteins in complex with eIF4E in the cap-bound and cap-free states. The
      structures reveal unexpected evolutionary plasticity in the eIF4E-binding mode,
      with a classical bipartite interface for Ce Mxt and a novel tripartite interface
      for Dm Mxt. Both interfaces comprise a canonical helix and a noncanonical helix
      that engage the dorsal and lateral surfaces of eIF4E, respectively. Remarkably,
      Dm Mxt contains a C-terminal auxiliary helix that lies anti-parallel to the
      canonical helix on the eIF4E dorsal surface. In contrast to the eIF4G and Ce Mxt
      complexes, the Dm eIF4E-Mxt complexes are resistant to competition by bipartite
      4E-BPs, suggesting that Dm Mxt can bind eIF4E when eIF4G binding is inhibited.
      Our results uncovered unexpected diversity in the binding modes of 4E-BPs,
      resulting in eIF4E complexes that display differential sensitivity to 4E-BP
      regulation. 

PMID- 26294657
TI  - Myeloid Suppressor Cells Accumulate and Regulate Blood Pressure in Hypertension.
AB  - RATIONALE: Chronic inflammation is a major contributor to the progressive
      pathology of hypertension, and T-cell activation is required for the genesis of
      hypertension. However, the precise role of myeloid cells in this process is
      unclear. OBJECTIVE: To characterize and understand the role of peripheral myeloid
      cells in the development of hypertension. METHODS AND RESULTS: We examined
      myeloid cells in the periphery of hypertensive mice and found that increased
      numbers of CD11b(+)Gr1(+) myeloid cells in blood and the spleen are a
      characteristic of 3 murine models of experimental hypertension (angiotensin II, L
      NG-nitroarginine methyl ester, and high salt). These cells express surface
      markers and transcription factors associated with immaturity and
      immunosuppression. Also, they produce hydrogen peroxide to suppress T-cell
      activation. These are characteristics of myeloid-derived suppressor cells
      (MDSCs). Depletion of hypertensive MDSCs increased blood pressure and renal
      inflammation. In contrast, adoptive transfer of wild-type MDSCs to hypertensive
      mice reduced blood pressure, whereas the transfer of nicotinamide adenine
      dinucleotide phosphate oxidase 2-deficient MDSCs did not. CONCLUSION: The
      accumulation of MDSCs is a characteristic of experimental models of hypertension.
      MDSCs limit inflammation and the increase of blood pressure through the
      production of hydrogen peroxide.

PMID- 26294660
TI  - Association between visceral and subcutaneous adipose depots and incident
      cardiovascular disease risk factors.
AB  - BACKGROUND: Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT)
      vary in volume and quality. We evaluated whether fat volume or attenuation
      (indirect measure of quality) predicts metabolic risk factor changes. METHODS AND
      RESULTS: Framingham Heart Study Multi-detector Computed Tomography Substudy
      participants (n=1730, 45% women) were followed up over a mean of 6.2 years.
      Baseline VAT and SAT volume (in cm(3)) and attenuation (in Hounsfield units) were
      assessed. Outcomes included blood pressure, lipids, and glucose. We constructed
      multivariable regression models predicting change from baseline to follow-up.
      Baseline VAT was associated with metabolic risk factors at follow-up. Per 500
      cm(3) increase in baseline VAT, glucose was 2.34 mg/dL higher (95% confidence
      interval, 1.71-2.97) and high-density lipoprotein was 1.62 mg/dL lower (95%
      confidence interval, 0.97-2.28) in women (P<0.0001 for both). These findings
      remained significant after adjustment for body mass index. Results for SAT were
      similar although less striking. Lower (more negative) fat attenuation was
      associated with more adverse metabolic profiles at follow-up. For example, per 5
      unit decrease in baseline VAT Hounsfield units, log triglycerides increased by
      0.08 mg/dL (95% confidence interval, 0.05-0.12; P=0.005), which remained
      significant after adjustment for baseline VAT. Among men, VAT and SAT Hounsfield
      units were associated with changes in cardiovascular disease risk factors but
      were mostly attenuated after baseline volume adjustment. CONCLUSIONS: VAT volume
      and SAT volume are associated with incident metabolic risk factors beyond overall
      adiposity. Decreases in fat attenuation are also associated with incident risk
      factors. These findings suggest that both volume and quality of VAT and SAT
      contribute to metabolic risk.

PMID- 26294661
TI  - Percutaneous Treatment of Recurrent In-Stent Restenosis of Carotid Artery
      Stenting: A Case Report and State-of-the-Art Review.
AB  - BACKGROUND: Restenosis after carotid artery stenting (CAS) is a poorly described
      phenomenon. Studies have reported a variable incidence ranging from 4% to 19.7%
      at 1 year of follow-up. Doppler Ultrasound (DUS) is now routinely used in the
      follow-up after CAS and endarterectomy with optimal accuracy in detecting
      significant restenosis, compared to digital subtraction angiography (DSA). CASE
      REPORT: We reported the case of a 76-year-old patient with evidence of recurrent
      severe in-stent restenosis (ISR) of the left internal carotid artery (ICA). In
      April 2007, due to evidence at DUS of severe left ICA disease, the patient
      underwent CAS. In January 2009, due to DUS evidence of severe ISR, the patient
      underwent balloon angioplasty. In September 2011, DUS showed a severe ISR with a
      peak systolic velocity (PSV) of 436 cm/s; in June 2012 angiography showed a sub
      expanded stent in the middle medial side with severe ISR (70%). Multiple
      inflations were performed and a slight residual sub-expansion of the lateral side
      of the stent was observed. Post-procedural DUS showed a reduction of PSV to 283
      cm/s and 266 cm/s at 1-month follow-up. An increasing value (322 cm/s) was
      noticed at 3-month follow-up DUS, while at 6-month follow-up DUS showed an
      important increase to 483 cm/s. Strict follow-up was adopted because of the
      patient's refusal of further treatment. CONCLUSIONS: Criteria for diagnosis of
      restenosis are not well established. The optimal treatment is still debated and
      no indications have been established, due to the lack of sufficient data.
      Approaches to ISR include percutaneous transluminal angioplasty, cutting-balloon
      angioplasty (CB-PTA), stenting, and drug-eluting balloon (DEB) angioplasty.
      Several studies indicate that endovascular treatment, including balloon
      angioplasty and (CB-PTA) alone or in conjunction with stenting, is the preferred
      strategy.

PMID- 26294662
TI  - Blood glucose fluctuation during Ramadan fasting in adolescents with type 1
      diabetes: findings of continuous glucose monitoring.

PMID- 26294663
TI  - Arterial Wall Elastic Properties and Endothelial Dysfunction in the Diabetic Foot
      Syndrome in Patients With Type 2 Diabetes.

PMID- 26294664
TI  - Limb salvage in patients with diabetes is not a temporary solution but a life
      changing procedure.

PMID- 26294665
TI  - Erroneous diabetes diagnosis: a case of HbA1c interference.

PMID- 26294666
TI  - A High-Throughput Method for the Analysis of Larval Developmental Phenotypes in
      Caenorhabditis elegans.
AB  - Caenorhabditis elegans postembryonic development consists of four discrete larval
      stages separated by molts. Typically, the speed of progression through these
      larval stages is investigated by visual inspection of the molting process. Here,
      we describe an automated method to monitor the timing of these discrete phases of
      C. elegans maturation, from the first larval stage through adulthood, using
      bioluminescence. The method was validated with a lin-42 mutant strain that shows
      delayed development relative to wild-type animals and with a daf-2 mutant that
      shows an extended second larval stage. This new method is inherently high
      throughput and will finally allow dissecting the molecular machinery governing
      the speed of the developmental clock, which has so far been hampered by the lack
      of a method suitable for genetic screens. 

PMID- 26294667
TI  - Preferential Breakpoints in the Recovery of Broken Dicentric Chromosomes in
      Drosophila melanogaster.
AB  - We designed a system to determine whether dicentric chromosomes in Drosophila
      melanogaster break at random or at preferred sites. Sister chromatid exchange in
      a Ring-X chromosome produced dicentric chromosomes with two bridging arms
      connecting segregating centromeres as cells divide. This double bridge can break
      in mitosis. A genetic screen recovered chromosomes that were linearized by
      breakage in the male germline. Because the screen required viability of males
      with this X chromosome, the breakpoints in each arm of the double bridge must be
      closely matched to produce a nearly euploid chromosome. We expected that most
      linear chromosomes would be broken in heterochromatin because there are no vital
      genes in heterochromatin, and breakpoint distribution would be relatively
      unconstrained. Surprisingly, approximately half the breakpoints are found in
      euchromatin, and the breakpoints are clustered in just a few regions of the
      chromosome that closely match regions identified as intercalary heterochromatin.
      The results support the Laird hypothesis that intercalary heterochromatin can
      explain fragile sites in mitotic chromosomes, including fragile X. Opened rings
      also were recovered after male larvae were exposed to X-rays. This method was
      much less efficient and produced chromosomes with a strikingly different array of
      breakpoints, with almost all located in heterochromatin. A series of circularly
      permuted linear X chromosomes was generated that may be useful for investigating
      aspects of chromosome behavior, such as crossover distribution and interference
      in meiosis, or questions of nuclear organization and function. 

PMID- 26294668
TI  - Regulation of Telomere Length Requires a Conserved N-Terminal Domain of Rif2 in
      Saccharomyces cerevisiae.
AB  - The regulation of telomere length equilibrium is essential for cell growth and
      survival since critically short telomeres signal DNA damage and cell cycle
      arrest. While the broad principles of length regulation are well established, the
      molecular mechanism of how these steps occur is not fully understood. We
      mutagenized the RIF2 gene in Saccharomyces cerevisiae to understand how this
      protein blocks excess telomere elongation. We identified an N-terminal domain in
      Rif2 that is essential for length regulation, which we have termed BAT domain for
      Blocks Addition of Telomeres. Tethering this BAT domain to Rap1 blocked telomere
      elongation not only in rif2Delta mutants but also in rif1Delta and rap1C-terminal
      deletion mutants. Mutation of a single amino acid in the BAT domain,
      phenylalanine at position 8 to alanine, recapitulated the rif2Delta mutant
      phenotype. Substitution of F8 with tryptophan mimicked the wild-type
      phenylalanine, suggesting the aromatic amino acid represents a protein
      interaction site that is essential for telomere length regulation. 

PMID- 26294669
TI  - The role of apolipoprotein A-IV in regulating glucagon-like peptide-1 secretion.
AB  - Both glucagon-like peptide-1 (GLP-1) and apolipoprotein A-IV (apoA-IV) are
      produced from the gut and enhance postprandial insulin secretion. This study
      investigated whether apoA-IV regulates nutrient-induced GLP-1 secretion and
      whether apoA-IV knockout causes compensatory GLP-1 release. Using lymph-fistula
      mice, we first determined lymphatic GLP-1 secretion by administering apoA-IV
      before an intraduodenal Ensure infusion. apoA-IV changed neither basal nor Ensure
      induced GLP-1 secretion relative to saline administration. We then assessed GLP-1
      in apoA-IV-/- and wild-type (WT) mice administered intraduodenal Ensure. apoA-IV
      /- mice had comparable lymph flow, lymphatic triglyceride, glucose, and protein
      outputs as WT mice. Intriguingly, apoA-IV-/- mice had higher lymphatic GLP-1
      concentration and output than WT mice 30 min after Ensure administration.
      Increased GLP-1 was also observed in plasma of apoA-IV-/- mice at 30 min. apoA-IV
      /- mice had comparable total gut GLP-1 content relative to WT mice under fasting,
      but a lower GLP-1 content 30 min after Ensure administration, suggesting that
      more GLP-1 was secreted. Moreover, an injection of apoA-IV protein did not
      reverse the increased GLP-1 secretion in apoA-IV-/- mice. Finally, we assessed
      gene expression of GLUT-2 and the lipid receptors, including G protein-coupled
      receptor (GPR) 40, GPR119, and GPR120 in intestinal segments. GLUT-2, GPR40 and
      GPR120 mRNAs were unaltered by apoA-IV knockout. However, ileal GPR119 mRNA was
      significantly increased in apoA-IV-/- mice. GPR119 colocalizes with GLP-1 in
      ileum and stimulates GLP-1 secretion by sensing OEA, lysophosphatidylcholine, and
      2-monoacylglycerols. We suggest that increased ileal GPR119 is a potential
      mechanism by which GLP-1 secretion is enhanced in apoA-IV-/- mice. 

PMID- 26294670
TI  - Short- and long-term regulation of intestinal Na+/H+ exchange by Toll-like
      receptors TLR4 and TLR5.
AB  - Inappropriate activation of pattern recognition receptors has been described as a
      potential trigger in the development of inflammatory bowel disease (IBD). In this
      study, we evaluated the activity and expression of Na(+)/H(+) exchanger (NHE)
      subtypes in T84 intestinal epithelial cells during Toll-like receptor 4 (TLR4)
      activation by monophosphoryl lipid A and TLR5 by flagellin. NHE activity and
      intracellular pH were evaluated by spectrofluorescence. Additionally, kinase
      activities were evaluated by ELISA, and siRNA was used to specifically inhibit
      adenylyl cyclase (AC). Monophosphoryl lipid A (MPLA) (0.01-50.00 MUg/ml) and
      flagellin (10-500 ng/ml) inhibited NHE1 activity in a concentration-dependent
      manner (MPLA short term -25.2 +/- 5.0%, long term -31.9 +/- 4.0%; flagellin short
      term -14.9 +/- 2.0%, long term -19.1 +/- 2.0%). Both ligands triggered AC3, PKA,
      PLC, and PKC signal molecules. Long-term exposure to flagellin and MPLA induced
      opposite changes on NHE3 activity; flagellin increased NHE3 activity (~10%) with
      overexpression of membrane protein, whereas MPLA decreased NHE3 activity (-17.3
      +/- 3.0%). MPLA and flagellin simultaneously had synergistic effects on NHE
      activity. MPLA and flagellin impaired pHi recovery after intracellular
      acidification. The simultaneous exposure to MPLA and flagellin induced a
      substantial pHi reduction (-0.55 +/- 0.03 pH units). Activation of TLR4 and TLR5
      exerts marked inhibition of NHE1 activity in intestinal epithelial cells.
      Transduction mechanisms set into motion during TLR4-mediated and long-term TLR5
      mediated inhibition of NHE1 activity involve AC3, PKA, PLC, and PKC. However,
      short- and long-term TLR4 activation and TLR5 activation might use different
      signaling pathways. The physiological alterations on intestinal epithelial cells
      described here may be useful in the development of better IBD therapeutics. 

PMID- 26294672
TI  - PAR-2 activation enhances weak acid-induced ATP release through TRPV1 and ASIC
      sensitization in human esophageal epithelial cells.
AB  - Esophageal visceral hypersensitivity has been proposed to be the pathogenesis of
      heartburn sensation in nonerosive reflux disease. Protease-activated receptor-2
      (PAR-2) is expressed in human esophageal epithelial cells and is believed to play
      a role in inflammation and sensation. PAR-2 activation may modulate these
      responses through adenosine triphosphate (ATP) release, which is involved in
      transduction of sensation and pain. The transient receptor potential vanilloid
      receptor 1 (TRPV1) and acid-sensing ion channels (ASICs) are both acid-sensitive
      nociceptors. However, the interaction among these molecules and the mechanisms of
      heartburn sensation are still not clear. We therefore examined whether ATP
      release in human esophageal epithelial cells in response to acid is modulated by
      TRPV1 and ASICs and whether PAR-2 activation influences the sensitivity of TRPV1
      and ASICs. Weak acid (pH 5) stimulated the release of ATP from primary human
      esophageal epithelial cells (HEECs). This effect was significantly reduced after
      pretreatment with 5-iodoresiniferatoxin (IRTX), a TRPV1-specific antagonist, or
      with amiloride, a nonselective ASIC blocker. TRPV1 and ASIC3 small interfering
      RNA (siRNA) transfection also decreased weak acid-induced ATP release.
      Pretreatment of HEECs with trypsin, tryptase, or a PAR-2 agonist enhanced weak
      acid-induced ATP release. Trypsin treatment led to the phosphorylation of TRPV1.
      Acid-induced ATP release enhancement by trypsin was partially blocked by IRTX,
      amiloride, or a PAR-2 antagonist. Conversely, acid-induced ATP release was
      augmented by PAR-2 activation through TRPV1 and ASICs. These findings suggested
      that the pathophysiology of heartburn sensation or esophageal hypersensitivity
      may be associated with the activation of PAR-2, TRPV1, and ASICs. 

PMID- 26294671
TI  - Intestinal DMT1 is critical for iron absorption in the mouse but is not required
      for the absorption of copper or manganese.
AB  - Divalent metal-ion transporter-1 (DMT1) is a widely expressed iron-preferring
      membrane-transport protein that serves a critical role in erythroid iron
      utilization. We have investigated its role in intestinal metal absorption by
      studying a mouse model lacking intestinal DMT1 (i.e., DMT1(int/int)).
      DMT1(int/int) mice exhibited a profound hypochromic-microcytic anemia,
      splenomegaly, and cardiomegaly. That the anemia was due to iron deficiency was
      demonstrated by the following observations in DMT1(int/int) mice: 1) blood iron
      and tissue nonheme-iron stores were depleted; 2) mRNA expression of liver
      hepcidin (Hamp1) was depressed; and 3) intraperitoneal iron injection corrected
      the anemia, and reversed the changes in blood iron, nonheme-iron stores, and
      hepcidin expression levels. We observed decreased total iron content in multiple
      tissues from DMT1(int/int) mice compared with DMT1(+/+) mice but no meaningful
      change in copper, manganese, or zinc. DMT1(int/int) mice absorbed (64)Cu and
      (54)Mn from an intragastric dose to the same extent as did DMT1(+/+) mice but the
      absorption of (59)Fe was virtually abolished in DMT1(int/int) mice. This study
      reveals a critical function for DMT1 in intestinal nonheme-iron absorption for
      normal growth and development. Further, this work demonstrates that intestinal
      DMT1 is not required for the intestinal transport of copper, manganese, or zinc. 

PMID- 26294673
TI  - Glial cell line-derived neurotrophic factor promotes barrier maturation and wound
      healing in intestinal epithelial cells in vitro.
AB  - Recent data suggest that neurotrophic factors from the enteric nervous system are
      involved in intestinal epithelial barrier regulation. In this context the glial
      cell line-derived neurotrophic factor (GDNF) was shown to affect gut barrier
      properties in vivo directly or indirectly by largely undefined processes in a
      model of inflammatory bowel disease (IBD). We further investigated the potential
      role and mechanisms of GDNF in the regulation of intestinal barrier functions.
      Immunostaining of human gut specimen showed positive GDNF staining in enteric
      neuronal plexus and in enterocytes. In Western blots of the intestinal epithelial
      cell lines Caco2 and HT29B6, significant amounts of GDNF were detected,
      suggesting that enterocytes represent an additional source of GDNF. Application
      of recombinant GDNF on Caco2 and HT29B6 cells for 24 h resulted in significant
      epithelial barrier stabilization in monolayers with immature barrier functions.
      Wound-healing assays showed a significantly faster closure of the wounded areas
      after GDNF application. GDNF augmented cAMP levels and led to significant
      inactivation of p38 MAPK in immature cells. Activation of p38 MAPK signaling by
      SB-202190 mimicked GDNF-induced barrier maturation, whereas the p38 MAPK
      activator anisomycin blocked GDNF-induced effects. Increasing cAMP levels had
      adverse effects on barrier maturation, as revealed by permeability measurements.
      However, increased cAMP augmented the proliferation rate in Caco2 cells, and GDNF
      induced proliferation of epithelial cells was abrogated by the PKA inhibitor H89.
      Our data show that enterocytes represent an additional source of GDNF synthesis.
      GDNF contributes to wound healing in a cAMP/PKA-dependent manner and promotes
      barrier maturation in immature enterocytes cells by inactivation of p38 MAPK
      signaling. 

PMID- 26294674
TI  - Maximal Admission Core Lesion Compatible With Favorable Outcome in Acute Stroke
      Patients Undergoing Endovascular Procedures.
AB  - BACKGROUND AND PURPOSE: Multiparametric imaging is meant to identify
      nonreversible lesions and predict on admission the minimum final infarct volume,
      a strong predictor of outcome. We aimed to confirm this hypothesis and define the
      maximal admission lesion volume compatible with favorable outcome (MALCOM).
      METHODS: We studied patients with internal carotid artery/middle cerebral artery
      occlusion selected with multiparametric computed tomography/magnetic resonance
      imaging, who underwent endovascular procedures. Admission infarct core was
      measured on initial cerebral blood volume-computed tomography perfusion or
      diffusion weighted imaging-magnetic resonance imaging. We defined percentage of
      lesion growth (final lesion admission core/admission core) and MALCOM: cutoff
      admission core volume above which probability of modified Rankin Scale 0 to 2 is
      <10%. RESULTS: Fifty-seven patients were studied (29 magnetic resonance imaging
      and 28 computed tomography perfusion). Mean core volume was 28+/-22 mL, and
      recanalization thrombolysis in cerebral ischemia 2b-3 was 77%. At 24 hours, mean
      infarct volume was 64+/-97 mL, and at 3 months modified Rankin Scale 0 to 2 was
      45%. Median lesion growth was smaller in recanalizers (16.7% versus 198.3%;
      P<0.01). MALCOM was 39 mL. When recanalization was achieved, 64% of patients
      within MALCOM (<39 mL) achieved favorable outcome, whereas despite recanalization
      only 12% of patients beyond MALCOM (>39 mL) achieved modified Rankin Scale 0 to 2
      (P=0.01). A regression model adjusted for age and recanalization showed that the
      only predictor of favorable outcome was having admission core lesion below MALCOM
      (OR: 9.3, 95% CI: 1.9-46.4; P<0.01). Analysis according to imaging modality
      showed that computed tomography-cerebral blood volume allowed larger MALCOM (42
      mL) than magnetic resonance-diffusion weighted imaging (29 mL). In octogenarians,
      MALCOM (15 mL) was lower in younger patients (40 mL). CONCLUSIONS: Admission
      lesion core is associated with final infarct volume and is a strong predictor of
      favorable outcome. MALCOM according to imaging modality and patient age could be
      set and used on admission to select candidates for endovascular procedures.

PMID- 26294675
TI  - Spouses of Stroke Survivors Report Reduced Health-Related Quality of Life Even in
      Long-Term Follow-Up: Results From Sahlgrenska Academy Study on Ischemic Stroke.
AB  - BACKGROUND AND PURPOSE: The consequences for the family of stroke survivor are
      generally studied in a short-term perspective. The aim of this study was to
      assess long-term aspects of health-related quality of life among spouses of
      stroke survivors. METHODS: Data on stroke survivors, controls, and spouses were
      collected from the 7-year follow-up of the Sahlgrenska Academy Study on Ischemic
      Stroke (SAHLSIS). The health-related quality of life of spouses was assessed by
      the Short Form-36, and the characteristics of stroke survivors were assessed
      using the National Institutes of Health Stroke Scale, the Mini-Mental State
      Examination, the Hospital Anxiety and Depression Scale, the Barthel Index, and
      the modified Rankin Scale. RESULTS: Dyads of 248 stroke survivors aged <70 at
      stroke onset and 245 dyads of matched controls were included. Spouses of stroke
      survivors and spouses of controls had a median age of 64 and 65, respectively;
      proportion of men was 35% and 34%, respectively. The spouses of stroke survivors
      reported lower scores in all the mental domains (P=0.045; P<0.001), as well as in
      the domains of general health (P=0.013) and physical role (P=0.006), compared
      with the spouses of controls. Predictors of poor physical health of the spouses
      were their own age and the level of global disability of the stroke survivor.
      Predictors of poor mental health of the spouses were depressive symptoms,
      cognitive impairment, and global disability among the stroke survivors.
      CONCLUSIONS: The health-related quality of life of spouses of stroke survivors is
      reduced not only during the first years but also in the long-term perspective.

PMID- 26294677
TI  - Prevalence and Risk Factors of Acute Incidental Infarcts.
AB  - BACKGROUND AND PURPOSE: The study of silent stroke has been limited to imaging of
      chronic infarcts; acute incidental infarcts (AII) detected on brain magnetic
      resonance imaging have been less investigated. This study aims to describe
      prevalence and risk factors of AII in a community and a clinic-based population.
      METHODS: Subjects were drawn from 2 ongoing studies: Epidemiology of Dementia in
      Singapore study, which is a subsample from a population-based study, and a clinic
      based case-control study. Subjects from both studies underwent similar clinical
      and neuropsychological assessments and brain magnetic resonance imaging.
      Prevalence of AII from these studies was determined. Subsequently, risk factors
      of AII were examined using multivariable logistic regression models. RESULTS: AII
      were seen in 7 of 623 (1.2%) subjects in Epidemiology of Dementia in Singapore
      (mean age, 70.9+/-6.8 years; 45% men) and in 12 of 389 (3.2%) subjects (mean age,
      72.1+/-8.3 years; 46% men) in the clinic-based study. AII were present in 0.8% of
      subjects with no cognitive impairment, 1.9% of those with cognitive impairment
      not dementia, and 4.2% of subjects with dementia. Significant association of AII
      was found with cerebral microbleeds (>=5) in the Epidemiology of Dementia in
      Singapore (odds ratio, 6.76; 95% confidence interval, 1.28-35.65; P=0.02) and in
      the clinic-based cohort (odds ratio, 4.65; 95% confidence interval, 1.39-15.53;
      P=0.01). There was no association of AII with hypertension, diabetes mellitus, or
      hyperlipidemia. CONCLUSIONS: AII are more likely to be present in those with
      cognitive impairment. Although a cause-effect relationship between the presence
      of AII and cognitive impairment is plausible, the association may be because of
      under-reporting of symptoms by individuals with cognitive impairment. The
      association between AII and cerebral microbleeds may indicate cerebral
      vasculopathy, independent of traditional vascular risk factors.

PMID- 26294678
TI  - Alcohol Use-Related Problems Among a Rural Indian Population of West Bengal: An
      Application of the Alcohol Use Disorders Identification Test (AUDIT).
AB  - AIMS: To examine alcohol use and related problems among a rural subset of the
      Indian population. METHODS: The Alcohol Use Disorders Identification Test (AUDIT)
      was used as part of Health and Demographic Surveillance of 36,611 individuals
      aged >=18 years. From this survey data on 3671 current alcohol users were
      analysed using bivariate and multivariate ordered logit regression. RESULTS: Over
      19% of males and 2.4% of females were current alcohol users. Mean ethanol
      consumption on a typical drinking day among males was estimated to be higher
      (96.3 gm) than females (56.5 gm). Mean AUDIT score was 11 among current alcohol
      users. AUDIT showed in the ordered logit regression estimated alcohol use-related
      problems to be low among women, Scheduled Tribes and unmarried people, whereas
      alcohol use-related problems registered high among Muslims. CONCLUSION: This
      rural population appears to be in need of an effective intervention program,
      perhaps targeting men and the household, aimed at reducing the level of alcohol
      use and related problems.

PMID- 26294676
TI  - Fluoxetine Maintains a State of Heightened Responsiveness to Motor Training Early
      After Stroke in a Mouse Model.
AB  - BACKGROUND AND PURPOSE: Data from both humans and animal models suggest that most
      recovery from motor impairment after stroke occurs in a sensitive period that
      lasts only weeks and is mediated, in part, by an increased responsiveness to
      training. Here, we used a mouse model of focal cortical stroke to test 2
      hypotheses. First, we investigated whether responsiveness to training decreases
      over time after stroke. Second, we tested whether fluoxetine, which can influence
      synaptic plasticity and stroke recovery, can prolong the period over which large
      training-related gains can be elicited after stroke. METHODS: Mice were trained
      to perform a skilled prehension task to an asymptotic level of performance after
      which they underwent stroke induction in the caudal forelimb area. The mice were
      then retrained after a 1- or 7-day delay with and without fluoxetine. RESULTS:
      Recovery of prehension after a caudal forelimb area stroke was complete if
      training was initiated 1 day after stroke but incomplete if it was delayed by 7
      days. In contrast, if fluoxetine was administered at 24 hours after stroke, then
      complete recovery of prehension was observed even with the 7-day training delay.
      Fluoxetine seemed to mediate its beneficial effect by reducing inhibitory
      interneuron expression in intact premotor cortex rather than through effects on
      infarct volume or cell death. CONCLUSIONS: There is a gradient of diminishing
      responsiveness to motor training over the first week after stroke. Fluoxetine can
      overcome this gradient and maintain maximal levels of responsiveness to training
      even 7 days after stroke.

PMID- 26294679
TI  - Balance Confidence and Fear of Falling Avoidance Behavior Are Most Predictive of
      Falling in Older Adults: Prospective Analysis.
AB  - BACKGROUND: Evidence suggests that there are several fall predictors in the
      elderly population, including previous fall history and balance impairment. To
      date, however, the role of psychological factors has not yet been thoroughly
      vetted in conjunction with physical factors as predictors of future falls.
      OBJECTIVE: The purpose of this study was to determine which measures, physical
      and psychological, are most predictive of falling in older adults. DESIGN: This
      was a prospective cohort study. METHODS: Sixty-four participants (mean age=72.2
      years, SD=7.2; 40 women, 24 men) with and without pathology (25 healthy, 17 with
      Parkinson disease, 11 with cerebrovascular accident, 6 with diabetes, and 5 with
      a cardiovascular diagnosis) participated. Participants reported fall history and
      completed physical-based measures (ie, Berg Balance Scale, Dynamic Gait Index,
      self-selected gait speed, Timed "Up & Go" Test, Sensory Organization Test) and
      psychological-based measures (ie, Fear of Falling Avoidance Behavior
      Questionnaire, Falls Efficacy Scale, Activities-specific Balance Confidence
      Scale). Contact was made 1 year later to determine falls during the subsequent
      year (8 participants lost at follow-up). RESULTS: Using multiple regression, fall
      history, pathology, and all measures were entered as predictor candidates. Three
      variables were included in the final model, explaining 49.2% of the variance:
      Activities-specific Balance Confidence Scale (38.7% of the variance), Fear of
      Falling Avoidance Behavior Questionnaire (5.6% additional variance), and Timed
      "Up & Go" Test (4.9% additional variance). LIMITATIONS: Falls were based on
      participant recall rather than a diary. CONCLUSIONS: Balance confidence was the
      best predictor of falling, followed by fear of falling avoidance behavior, and
      the Timed "Up & Go" Test. Fall history, presence of pathology, and physical tests
      did not predict falling. These findings suggest that participants may have had a
      better sense of their fall risk than with a test that provides a snapshot of
      their balance.

PMID- 26294680
TI  - Effectiveness and Cost-Effectiveness of Different Weekly Frequencies of Pilates
      for Chronic Low Back Pain: Randomized Controlled Trial.
AB  - BACKGROUND: The Pilates method has been recommended to patients with low back
      pain, but the evidence on effectiveness is inconclusive. In addition, there is
      still no evidence for the cost-effectiveness of this method or for the ideal
      number of sessions to achieve the highest effectiveness. OBJECTIVE: The aim of
      this study will be to investigate the effectiveness and cost-effectiveness of the
      Pilates method with different weekly frequencies in the treatment of patients
      with nonspecific low back pain. DESIGN: This is a randomized controlled trial
      with blinded assessor. SETTING: This study will be conducted at a physical
      therapy clinic in Sao Paulo, Brazil. PARTICIPANTS: Two hundred ninety-six
      patients with nonspecific low back pain between the ages of 18 and 80 years will
      be assessed and randomly allocated to 4 groups (n=74 patients per group).
      INTERVENTION: All groups will receive an educational booklet. The booklet group
      will not receive additional exercises. Pilates group 1 will follow a Pilates
      based program once a week, Pilates group 2 will follow the same program twice a
      week, and Pilates group 3 will follow the same program 3 times a week. The
      intervention will last 6 weeks. MEASUREMENTS: A blinded assessor will evaluate
      pain, quality-adjusted life-years, general and specific disability,
      kinesiophobia, pain catastrophizing, and global perceived effect 6 weeks, 6
      months, and 12 months after randomization. LIMITATIONS: Therapists and patients
      will not be blinded. CONCLUSIONS: This will be the first study to investigate
      different weekly frequencies of treatment sessions for nonspecific low back pain.
      The results of this study will contribute to a better definition of treatment
      programs for this population.

PMID- 26294681
TI  - Are CMS G-Code Functional Limitation Severity Modifiers Responsive to Change
      Across an Episode of Outpatient Rehabilitation?
AB  - BACKGROUND: The Centers for Medicare & Medicaid Services has mandated
      rehabilitation professionals to document patients' impairment levels. There is no
      evidence of responsiveness to change of functional limitation severity modifier
      codes. OBJECTIVE: The purpose of this study was to assess the validity of G-code
      functional limitation severity modifier codes in determining change in function.
      DESIGN: This was a retrospective observational study. METHODS: Patients completed
      the Activity Measure for Post-Acute Care (AM-PAC) and were assigned G-codes, with
      severity modifiers based on AM-PAC scores at initial and follow-up visits.
      Patients were classified as having AM-PAC scores in the upper or lower range for
      each severity modifier, and sensitivity, specificity, and positive and negative
      predictive values for change in severity modifier level and odds of changing by
      one severity modifier level using a change in AM-PAC score of at least 1 minimal
      detectable change at the 95% confidence interval (MDC95) as the standard were
      determined. RESULTS: Sensitivity and specificity of change in severity modifier
      in determining change in function were dependent on patients' initial AM-PAC
      scores. Improvement in severity modifier level was 2.2 to 4.5 times more likely
      with scores at the higher end of the range within a severity modifier level than
      with scores in the lower end of the range. Decline in severity modifier level was
      2.7 to 4.8 times more likely with scores at the lower end of the range within a
      severity modifier than with scores in the higher end of the range. LIMITATIONS:
      Data were from one health care system, and most patients had orthopedic
      conditions. The MDC95 for AM-PAC tool may not be the best standard for defining
      functional change. CONCLUSIONS: The G-code functional limitation severity
      modifier system may not be valid for determining change in function and is not
      recommended for determining if patients have changed over the course of
      outpatient therapy.

PMID- 26294682
TI  - Characteristics of US-Licensed Foreign-Educated Physical Therapists.
AB  - BACKGROUND: Foreign-educated physical therapists are often viewed as one possible
      solution to the current shortage of physical therapists, yet there is very little
      research regarding these individuals. OBJECTIVE: The purpose of this study was to
      describe those physical therapists who are licensed in the United States but who
      were educated in another country. This description includes their country of
      education, their employment patterns, and the reasons they decided to emigrate
      and work as a physical therapist in the United States. DESIGN: A cross-sectional
      survey was conducted. METHODS: An electronic survey was sent to all physical
      therapists currently licensed in the United States who had been educated in
      another country. Those who had been licensed within the last 5 years are
      reported. RESULTS: The results of the survey indicated that the typical foreign
      educated physical therapist is female, aged 32.2 years, and was born and trained
      in either the Philippines or India. A majority of foreign-educated physical
      therapists obtained their first license in New York, Michigan, Illinois, Texas,
      or Florida. The most common reasons cited as to why a particular jurisdiction was
      chosen for initial employment were "recruiter recommendation," "family, spouse,
      partner, or friends," "ease of the licensure process," and "ability to secure a
      visa sponsor." A majority of foreign-educated physical therapists in this study
      initially worked in a skilled nursing facility, a long-term care or extended care
      facility, or a home health setting. LIMITATIONS: Only those foreign-educated
      physical therapists licensed within the last 5 years are reported. CONCLUSIONS:
      This study is the first to report on foreign-educated physical therapists in the
      United States. The findings of this study will provide important and useful
      information to others dealing with physical therapy professional and workforce
      issues.

PMID- 26294683
TI  - Effectiveness of Manual Therapy and Therapeutic Exercise for Temporomandibular
      Disorders: Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Manual therapy (MT) and exercise have been extensively used to treat
      people with musculoskeletal conditions such as temporomandibular disorders (TMD).
      The evidence regarding their effectiveness provided by early systematic reviews
      is outdated. PURPOSE: The aim of this study was to summarize evidence from and
      evaluate the methodological quality of randomized controlled trials that examined
      the effectiveness of MT and therapeutic exercise interventions compared with
      other active interventions or standard care for treatment of TMD. DATA SOURCES:
      Electronic data searches of 6 databases were performed, in addition to a manual
      search. STUDY SELECTION: Randomized controlled trials involving adults with TMD
      that compared any type of MT intervention (eg, mobilization, manipulation) or
      exercise therapy with a placebo intervention, controlled comparison intervention,
      or standard care were included. The main outcomes of this systematic review were
      pain, range of motion, and oral function. Forty-eight studies met the inclusion
      criteria and were analyzed. DATA EXTRACTION: Data were extracted in duplicate on
      specific study characteristics. DATA SYNTHESIS: The overall evidence for this
      systematic review was considered low. The trials included in this review had
      unclear or high risk of bias. Thus, the evidence was generally downgraded based
      on assessments of risk of bias. Most of the effect sizes were low to moderate,
      with no clear indication of superiority of exercises versus other conservative
      treatments for TMD. However, MT alone or in combination with exercises at the jaw
      or cervical level showed promising effects. LIMITATIONS: Quality of the evidence
      and heterogeneity of the studies were limitations of the study. CONCLUSIONS: No
      high-quality evidence was found, indicating that there is great uncertainty about
      the effectiveness of exercise and MT for treatment of TMD.

PMID- 26294685
TI  - Scoring criteria for portable monitor recordings: a comparison of four hypopnoea
      definitions in a population-based cohort.
AB  - RATIONALE: Limited-channel portable monitors (PMs) are increasingly used as an
      alternative to polysomnography (PSG) for the diagnosis of obstructive sleep
      apnoea (OSA). However, recommendations for the scoring of PM recordings are still
      lacking. Pulse-wave amplitude (PWA) drops, considered as surrogates for EEG
      arousals, may increase the detection sensitivity for respiratory events in PM
      recordings. OBJECTIVES: To investigate the performance of four different
      hypopnoea scoring criteria, using 3% or 4% oxygen desaturation levels, including
      or not PWA drops as surrogates for EEG arousals, and to determine the impact of
      measured versus reported sleep time on OSA diagnosis. METHODS: Subjects drawn
      from a population-based cohort underwent a complete home PSG. The PSG recordings
      were scored using the 2012 American Academy of Sleep Medicine criteria to
      determine the apnoea-hypopnoea index (AHI). Recordings were then rescored using
      only parameters available on type 3 PM devices according to different hypopnoea
      criteria and patients-reported sleep duration to determine the 'portable monitor
      AHIs' (PM-AHIs). MAIN RESULTS: 312 subjects were included. Overall, PM-AHIs
      showed a good concordance with the PSG-based AHI although it tended to slightly
      underestimate it. The PM-AHI using 3% desaturation without PWA drops showed the
      best diagnostic accuracy for AHI thresholds of >= 5/h and >= 15/h (correctly
      classifying 94.55% and 93.27% of subjects, respectively, vs 80.13% and 87.50%
      with PWA drops). There was a significant but modest correlation between PWA drops
      and EEG arousals (r=0.20, p=0.0004). CONCLUSION: Interpretation of PM recordings
      using hypopnoea criteria which include 3% desaturation without PWA drops as EEG
      arousal surrogate showed the best diagnosis accuracy compared with full PSG.

PMID- 26294684
TI  - Facilitating Community-Based Exercise for People With Stroke: Cross-Sectional e
      Survey of Physical Therapist Practice and Perceived Needs.
AB  - BACKGROUND: Educating people with stroke about community-based exercise programs
      (CBEPs) is a recommended practice that physical therapists are well positioned to
      implement. OBJECTIVE: The aim of this study was to evaluate the provision of
      education about CBEPs to people with stroke, barriers to providing education, and
      preferences for resources to facilitate education among physical therapists in
      neurological practice. DESIGN: A cross-sectional e-survey of physical therapists
      treating adults with stroke in Ontario, Canada, was conducted. METHODS: A link to
      the questionnaire was emailed to physical therapists in a provincial stroke
      network, a provincial physical therapy association, and on hospital and previous
      research lists. RESULTS: Responses from 186 physical therapists were analyzed.
      The percentage of respondents who reported providing CBEP education was 84.4%.
      Only 36.6% reported typically providing education to >=7 out of 10 patients with
      stroke. Physical (90.5%) and preventative (84.6%) health benefits of exercise
      were most frequently discussed. Therapists reported most commonly delivering
      education at discharge (73.7%). Most frequently cited barriers to educating
      patients were a perceived lack of suitable programs (53.2%) and a lack of
      awareness of local CBEPs (23.8%). Lists of CBEPs (94.1%) or brochures (94.1%)
      were considered to be facilitators. The percentage of physical therapists
      providing CBEP education varied across acute, rehabilitation, and public
      outpatient settings. LIMITATIONS: The percentage of physical therapists providing
      education may have been overestimated if respondents who deliver CBEP education
      were more likely to participate and if participants answered in a socially
      desirable way. CONCLUSIONS: Even though a high proportion of physical therapists
      provide CBEP education, education is not consistently delivered to the majority
      of patients poststroke. Although a CBEP list or brochure would facilitate
      education regarding existing CBEPs, efforts to implement CBEPs are needed to help
      overcome the lack of suitable programs.

PMID- 26294686
TI  - Regulation of alternative splicing in Drosophila by 56 RNA binding proteins.
AB  - Alternative splicing is regulated by RNA binding proteins (RBPs) that recognize
      pre-mRNA sequence elements and activate or repress adjacent exons. Here, we used
      RNA interference and RNA-seq to identify splicing events regulated by 56
      Drosophila proteins, some previously unknown to regulate splicing. Nearly all
      proteins affected alternative first exons, suggesting that RBPs play important
      roles in first exon choice. Half of the splicing events were regulated by
      multiple proteins, demonstrating extensive combinatorial regulation. We observed
      that SR and hnRNP proteins tend to act coordinately with each other, not
      antagonistically. We also identified a cross-regulatory network where splicing
      regulators affected the splicing of pre-mRNAs encoding other splicing regulators.
      This large-scale study substantially enhances our understanding of recent models
      of splicing regulation and provides a resource of thousands of exons that are
      regulated by 56 diverse RBPs. 

PMID- 26294687
TI  - Extensive cross-regulation of post-transcriptional regulatory networks in
      Drosophila.
AB  - In eukaryotic cells, RNAs exist as ribonucleoprotein particles (RNPs). Despite
      the importance of these complexes in many biological processes, including
      splicing, polyadenylation, stability, transportation, localization, and
      translation, their compositions are largely unknown. We affinity-purified 20
      distinct RNA-binding proteins (RBPs) from cultured Drosophila melanogaster cells
      under native conditions and identified both the RNA and protein compositions of
      these RNP complexes. We identified "high occupancy target" (HOT) RNAs that
      interact with the majority of the RBPs we surveyed. HOT RNAs encode components of
      the nonsense-mediated decay and splicing machinery, as well as RNA-binding and
      translation initiation proteins. The RNP complexes contain proteins and mRNAs
      involved in RNA binding and post-transcriptional regulation. Genes with the
      capacity to produce hundreds of mRNA isoforms, ultracomplex genes, interact
      extensively with heterogeneous nuclear ribonuclear proteins (hnRNPs). Our data
      are consistent with a model in which subsets of RNPs include mRNA and protein
      products from the same gene, indicating the widespread existence of auto
      regulatory RNPs. From the simultaneous acquisition and integrative analysis of
      protein and RNA constituents of RNPs, we identify extensive cross-regulatory and
      hierarchical interactions in post-transcriptional control. 

PMID- 26294689
TI  - The impact of interruptions on the duration of nursing interventions: a direct
      observation study in an academic emergency department.
AB  - BACKGROUND: Interruptions to nursing workload may contribute to procedural
      failures and clinical errors impacting quality/safety of care, but the impact of
      interruptions on the duration of these activities has not been closely
      scrutinised. This study analyses the effect of interruptions to care provided by
      nurses and clinical technicians on the length of clinical procedures and
      interventions (excluding the length of the interruption). METHODS: An
      observational time study of the effect of interruptions on common nursing
      interventions in the emergency department (ED) of a large academic medical centre
      was conducted. This study used direct observations of nurses and clinical
      technicians while delivering care to patients. RESULTS: The average time spent on
      an uninterrupted intervention was 296.47 s (median:185.15, SD:319.05), while
      interrupted interventions took 682.02 s (median:589.63, SD:504.59). Controlling
      for intervention type and other potential confounding factors using multiple
      linear regression found that interrupted interventions were 121.36 s (95% CI
      79.57 to 163.15) longer, a 19 percentage point increase (95% CI 11.31 to 26.89),
      than an intervention without (excluding the length of the interruption).
      Family/patient interruptions effected duration the most while staff interruptions
      affected the intervention time the least. DISCUSSION: Our findings are consistent
      with outcomes of studies in non-healthcare domains, but are contrary to a study
      of ED physicians, suggesting differential responses to interruptions by
      physicians and nurses. Future studies on interruptions in healthcare should thus
      be discipline specific. Though the effect of interruptions on intervention length
      is only about 2 min, in an ED setting, this can increase patient risks and costs.
      To better focus efforts to reduce interruptions future research should focus on
      further separation of interruption type (eg, urgent vs routine or unnecessary).

PMID- 26294690
TI  - The untidy margins of ethical approval.

PMID- 26294688
TI  - DIS3 shapes the RNA polymerase II transcriptome in humans by degrading a variety
      of unwanted transcripts.
AB  - Human DIS3, the nuclear catalytic subunit of the exosome complex, contains
      exonucleolytic and endonucleolytic active domains. To identify DIS3 targets
      genome-wide, we combined comprehensive transcriptomic analyses of engineered
      HEK293 cells that expressed mutant DIS3, with Photoactivatable Ribonucleoside
      Enhanced Cross-Linking and Immunoprecipitation (PAR-CLIP) experiments. In cells
      expressing DIS3 with both catalytic sites mutated, RNAs originating from
      unannotated genomic regions increased ~2.5-fold, covering ~70% of the genome and
      allowing for thousands of novel transcripts to be discovered. Previously
      described pervasive transcription products, such as Promoter Upstream Transcripts
      (PROMPTs), accumulated robustly upon DIS3 dysfunction, representing a significant
      fraction of PAR-CLIP reads. We have also detected relatively long putative
      premature RNA polymerase II termination products of protein-coding genes whose
      levels in DIS3 mutant cells can exceed the mature mRNAs, indicating that
      production of such truncated RNA is a common phenomenon. In addition, we found
      DIS3 to be involved in controlling the formation of paraspeckles, nuclear bodies
      that are organized around NEAT1 lncRNA, whose short form was overexpressed in
      cells with mutated DIS3. Moreover, the DIS3 mutations resulted in misregulation
      of expression of ~50% of transcribed protein-coding genes, probably as a
      secondary effect of accumulation of various noncoding RNA species. Finally, cells
      expressing mutant DIS3 accumulated snoRNA precursors, which correlated with a
      strong PAR-CLIP signal, indicating that DIS3 is the main snoRNA-processing
      enzyme. EXOSC10 (RRP6) instead controls the levels of the mature snoRNAs.
      Overall, we show that DIS3 has a major nucleoplasmic function in shaping the
      human RNA polymerase II transcriptome. 

PMID- 26294691
TI  - Club drugs: what's happening?

PMID- 26294692
TI  - High rates of recreational drug use in men who have sex with men.

PMID- 26294693
TI  - Can we use postal surveys with anonymous testing to monitor chlamydia prevalence
      in young women in England? Pilot study incorporating randomised controlled trial
      of recruitment methods.
AB  - OBJECTIVES: Chlamydia prevalence in the general population is a potential outcome
      measure for the evaluation of chlamydia control programmes. We carried out a
      pilot study to determine the feasibility of using a postal survey for population
      based chlamydia prevalence monitoring. METHODS: Postal invitations were sent to a
      random sample of 2000 17-year-old to 18-year-old women registered with a general
      practitioner in two pilot areas in England. Recipients were randomised to receive
      either a self-sampling kit (n=1000), a self-sampling kit and offer of L5 voucher
      on return of sample (n=500) or a self-sampling kit on request (n=500).
      Participants returned a questionnaire and self-taken vulvovaginal swab sample for
      unlinked anonymous Chlamydia trachomatis testing. Non-responders were sent a
      reminder letter 3 weeks after initial invitation. We calculated the participation
      rate (number of samples returned/number of invitations sent) and cost per sample
      returned (including cost of consumables and postage) in each group. RESULTS: A
      total of 155/2000 (7.8%) samples were returned with consent for testing.
      Participation rates varied by invitation group: 7.8% in the group who were
      provided with a self-sampling kit, 14% in the group who were also offered a
      voucher and 1.0% in the group who were not sent a kit. The cost per sample
      received was lowest (L36) in the group who were offered both a kit and a voucher.
      CONCLUSIONS: The piloted survey methodology achieved low participation rates.
      This approach is not suitable for population-based monitoring of chlamydia
      prevalence among young women in England. STUDY REGISTRATION NUMBER: (UKCRN ID
      10913).

PMID- 26294694
TI  - Bilothorax as a complication of percutaneous transhepatic biliary drainage.
AB  - We report two cases of bilothorax that occurred as a complication of percutaneous
      transhepatic biliary drainage. In an 86-year-old woman who had undergone
      percutaneous transhepatic biliary drainage for obstructive jaundice, bilothorax
      occurred after accidental removal of the tube. She recovered with chest drainage
      only. An 83-year-old man who had undergone percutaneous transhepatic biliary
      drainage for cholecystitis developed bilothorax with infection. He recovered with
      thoracoscopic curettage. Although bilothorax is a rare complication of
      percutaneous transhepatic biliary drainage, appropriate diagnosis and prompt
      treatment is important, especially when bilothorax is accompanied by infection. 

PMID- 26294696
TI  - High-dose vitamin D supplementation and liver histology in NASH.

PMID- 26294695
TI  - Faecal haemoglobin and faecal calprotectin as indicators of bowel disease in
      patients presenting to primary care with bowel symptoms.
AB  - OBJECTIVE: In primary care, assessing which patients with bowel symptoms harbour
      significant disease (cancer, higher-risk adenoma or IBD) is difficult. We studied
      the diagnostic accuracies of faecal haemoglobin (FHb) and faecal calprotectin
      (FC) in a cohort of symptomatic patients. DESIGN: From October 2013 to March
      2014, general practitioners were prompted to request FHb and FC when referring
      patients with bowel symptoms to secondary care. Faecal samples were analysed for
      haemoglobin (EIKEN OC-Sensor io) and calprotectin (BUHLMANN Calprotectin ELISA).
      Patients triaged to endoscopy were investigated within 6 weeks. All clinicians
      and endoscopists were blind to the faecal test results. The diagnostic accuracies
      of FHb and FC for identification of significant bowel disease were assessed.
      RESULTS: 1043 patients returned samples. FHb was detectable in 57.6% (median 0.4
      ug/g, 95% CI 0.4 to 0.8; range 0-200). FC at 50 ug/g or above was present in
      60.0%. 755 patients (54.6% women, median age 64 years (range 16-90, IQR 52-73))
      returned samples and completed colonic investigations. 103 patients had
      significant bowel disease; the negative predictive values of FHb for colorectal
      cancer, higher-risk adenoma and IBD were 100%, 97.8% and 98.4%, respectively.
      Using cut-offs of detectable FHb and/or 200 ug/g FC detected two further cases of
      IBD, one higher-risk adenoma and no additional cancers. CONCLUSIONS: In primary
      care, undetectable FHb is a good 'rule-out' test for significant bowel disease
      and could guide who requires investigation.

PMID- 26294697
TI  - Not Calm and Aminoff Suffering Syndrome in Advanced Alzheimer's Disease.
AB  - We studied 183 patients with advanced dementia who had been admitted to the
      Geriatric-Internal Medicine Department of a general hospital, with a 1 year
      follow-up evaluated by Mini-Suffering State Examination (MSSE) scores on first
      days after admission. The not calm compared to calm patients with advanced
      dementia had a high suffering level (6.12 +/- 2.16 versus 3.21 +/- 1.71) with a
      statistically significant difference (P = 0.001). The not calm patients were
      sicker, a higher percentage had fever (P = 0.005), elevated levels of white blood
      cells WBC (P = 0.003) and C-reactive protein (CRP) (P = 0.020). The Kaplan-Meier
      function analysis showed a shorter survival of not calm versus calm advanced
      dementia patients, with a statistically significant difference (Log Rank [Mantel
      Cox] P = 0.002). Not calm in advanced dementia patients is the first item of the
      MSSE and is a very important symptom of Aminoff Suffering Syndrome. 

PMID- 26294698
TI  - Partnering With a Family Advisor to Improve Communication in a Pediatric
      Intensive Care Unit.
AB  - Inadequate communication between medical teams and families can lead to errors
      and poor-quality care. The objective was to understand why communication between
      the clinical team and families was not occurring consistently in the pediatric
      intensive care unit and improve the system using a multidisciplinary improvement
      team including a family advisor. This improvement project used Lean Six Sigma.
      The team observed updates and collected documented communication, survey,
      interview, and focus group data from families and staff. Root causes of failures
      included lack of assigned responsibility, lack of defined daily update, and lack
      of a daily communication standard. Process changes were implemented, resulting in
      an increased mean documented communication rate from 13% pre intervention to 65%
      post intervention that was sustained for more than 2 years (P < .001). Including
      a family advisor as an equal member of an improvement team provides family
      empowerment and a greater chance of success in complex areas.

PMID- 26294699
TI  - Evaluation of Eradication Rates for Macrolide-Based Treatment of Helicobacter
      pylori Infection in an Era of Increasing Resistance.

PMID- 26294700
TI  - Cardiovascular disease in military populations: introduction and overview.

PMID- 26294701
TI  - Screening for cardiac disease in potential recruits to the British Army.
AB  - The British Army screens potential recruits for disease, including cardiovascular
      disease, at the pre-employment medical assessment in the Army Selection Centres.
      The epidemiology of cardiovascular disease in the Armed Forces coupled with the
      high physical demand placed on the cardiovascular system, often in remote
      locations make screening desirable. This is particularly pertinent as servicemen
      and women die from cardiovascular disease each year. To evaluate this particular
      screening system it is essential to understand the aim of the system, how it is
      designed and how screening systems in general are evaluated. The efficacy of a
      screening test is quantified using the measurements of sensitivity, specificity
      and likelihood ratios. These measurements are defined and the pitfalls associated
      with evaluating a screening system are described. The different screening tests
      used to identify cardiac disease and their individual strengths and weaknesses,
      are illustrated. Finally the article reviews the previous British Army recruit
      cardiac screening system, that used a stereotyped history and physical
      examination and the newer system that replaced it, which includes the
      incorporation of the 12-lead ECG and on site echocardiography in individuals
      revealing abnormalities on history, examination or ECG. 

PMID- 26294702
TI  - Clinical and Translational Research: Expanding Opportunities!

PMID- 26294703
TI  - Solid pseudopapillary neoplasm of the pancreas head in a pregnant woman: safe
      pancreaticoduodenectomy postpartum.
AB  - Solid pseudopapillary neoplasms (SPNs) of the pancreas are rare and typically
      arise in young women. The optimal management of a pregnant woman suspected of
      having an SPN of the pancreas head is unclear. We report such a case where close
      monitoring for tumor growth was done during pregnancy and a successful
      pancreaticoduodenectomy was performed after term delivery. 

PMID- 26294705
TI  - A Vets Recovery.

PMID- 26294704
TI  - Inflammatory Markers in Recent Onset Psychosis and Chronic Schizophrenia.
AB  - BACKGROUND: Immune markers have been associated with schizophrenia, but few
      studies have examined multiple markers in both recent onset and chronic
      schizophrenia patients. METHODS: The sample of 588 individuals included 79 with
      recent onset psychosis, 249 with chronic schizophrenia, and 260 controls. A
      combined inflammation score was calculated by principal components factor
      analysis of the levels of C-reactive protein, Pentraxin 3, and IgG antibodies to
      gliadin, casein, and Saccharomyces cerevisiae measured in blood samples.
      Inflammation scores among groups were compared by multivariate analyses. RESULTS:
      The chronic schizophrenia group showed significant elevations in the combined
      inflammation score compared with controls. The recent onset group surprisingly
      showed a reduction in the combined inflammation score. Consistent with these
      findings, the chronic schizophrenia group had significantly increased odds of a
      combined inflammation score greater than the 75th and the 90th percentile of that
      of the controls. The recent onset group had significantly increased odds of a
      combined inflammation score less than the 10th and the 25th percentile level of
      the controls. CONCLUSIONS: The recent onset of psychosis may be associated with
      inherent deficits in innate immunity. Individuals later in the course of disease
      may have increased levels of innate immunity. The reasons for these changes are
      not known with certainty but may be related to compensatory increases as the
      disease progresses. Longitudinal studies are needed to determine the course of
      immune abnormalities in schizophrenia and their role in the clinical
      manifestations of the disorder.

PMID- 26294707
TI  - Structural housing elements associated with home injuries in children.
AB  - OBJECTIVE: To quantify unintentional injuries associated with housing elements
      among children less than 18 years old treated in US hospital emergency
      departments. METHODS: The National Electronic Injury Surveillance System (NEISS)
      coding manual was reviewed, and all product codes that identified products
      permanently affixed to a home (housing elements) were identified. A query of the
      2008 NEISS data for children under 18 determined the numbers of cases by severity
      code for each identified housing element. Housing elements were then tabulated by
      the number of cases for each severity code. The top 10 cases by severity code,
      (1) hospitalised or (2) treated in emergency departments, were included in a case
      review. Ten per cent of all cases or a minimum of 100 cases were randomly
      selected for review for each of the identified housing elements to assess if the
      case description could inform prevention efforts. RESULTS: Twelve housing
      elements (bathtub, cabinet, carpet, ceiling/wall, counter, door, fence, floor,
      nail, porch, stairs and window) were identified as the leading causes of injuries
      resulting in hospitalisations or emergency department visits. A list of potential
      interventions was generated based on the review of the case histories. Suggested
      changes for NEISS coding are also offered to enhance future prevention research.
      CONCLUSIONS: NEISS is a valuable tool to identify home injury risks and inform
      design decisions for housing elements. Improved understanding of housing elements
      associated with injuries has the potential to enhance home inspection forms.
      However, interpretation of NEISS results is limited by lack of clarity about how
      the housing element was involved in the injury event.

PMID- 26294706
TI  - Longitudinal Course of Clients With Co-occurring Schizophrenia-Spectrum and
      Substance Use Disorders in Urban Mental Health Centers: A 7-Year Prospective
      Study.
AB  - OBJECTIVE: A previous longitudinal study in rural New Hampshire showed that
      community mental health center clients with co-occurring schizophrenia-spectrum
      and substance use disorders (SZ/SUD) improved steadily and substantially over 10
      years. The current study examined 7 years of prospective clinical and functional
      outcomes among inner-city Connecticut (CT) community mental health center clients
      with SZ/SUD. METHOD: Participants were 150 adults with SZ/SUD, selected for high
      service needs, in 2 inner-city mental health centers in CT. Initially, all
      received integrated mental health and substance abuse treatments for at least the
      first 3 years as part of a clinical trial. Assessments at baseline and yearly
      over 7 years measured progress toward 6 target clinical and functional outcomes:
      absence of psychiatric symptoms, remission of substance abuse, independent
      housing, competitive employment, social contact with non-users of substances, and
      life satisfaction. RESULTS: The CT SZ/SUD participants improved significantly on
      5 of the 6 main outcomes: absence of psychiatric symptoms (45%-70%), remission of
      substance use disorders (8%-61%), independent housing (33%-47%), competitive
      employment (14%-28%), and life satisfaction (35%-53%). Only social contact with
      nonusers of substances was unimproved (14%-17%). CONCLUSIONS: Many urban
      community mental health center clients with SZ/SUD and access to integrated
      treatment improve significantly on clinical, vocational, residential, and life
      satisfaction outcomes over time, similar to clients with SZ/SUD in rural areas.
      Thus, the long-term course for people with SZ/SUD is variable but often quite
      positive.

PMID- 26294709
TI  - Resilient health care: turning patient safety on its head.
AB  - The current approach to patient safety, labelled Safety I, is predicated on a
      'find and fix' model. It identifies things going wrong, after the event, and aims
      to stamp them out, in order to ensure that the number of errors is as low as
      possible. Healthcare is much more complex than such a linear model suggests. We
      need to switch the focus to what we have come to call Safety II: a concerted
      effort to enable things to go right more often. The key is to appreciate that
      healthcare is resilient to a large extent, and everyday performance succeeds much
      more often than it fails. Clinicians constantly adjust what they do to match the
      conditions. Facilitating work flexibility, and actively trying to increase the
      capacity of clinicians to deliver more care more effectively, is key to this new
      paradigm. At its heart, proactive safety management focuses on how everyday
      performance usually succeeds rather than on why it occasionally fails, and
      actively strives to improve the former rather than simply preventing the latter. 

PMID- 26294708
TI  - Relationships between community social capital and injury in Canadian
      adolescents: a multilevel analysis.
AB  - BACKGROUND: Characteristics of social environments are potential risk factors for
      adolescent injury. Impacts of social capital on the occurrence of such injuries
      have rarely been explored. METHODS: General health questionnaires were completed
      by 8910 youth aged 14 years and older as part of the 2010 Canadian Health
      Behaviour in School-Aged Children study. These were supplemented with community
      level data from the 2006 Canada Census of Population. Multilevel logistic
      regression models with random intercepts were fit to examine associations of
      interest. The reliability and validity of variables used in this analysis had
      been established in past studies, or in new analyses that employed factor
      analysis. RESULTS: Between school differences explained 2% of the variance in the
      occurrence of injuries. After adjustment for all confounders, community social
      capital did not have any impact on the occurrence of injuries in boys: OR: 1.01,
      95% CI 0.80 to 1.29. However, living in areas with low social capital was
      associated with lower occurrence of injuries in girls (OR 0.78, 95% CI 0.63 to
      0.96). Other factors that were significantly related to injuries in both genders
      were younger age, engagement in more risky behaviours, and negative behavioural
      influences from peers. CONCLUSIONS: After simultaneously taking into account the
      influence of community-level and individual-level factors, community levels of
      social capital remained a relatively strong predictor of injury among girls but
      not boys. Such gender effects provide important clues into the social aetiology
      of youth injury.

PMID- 26294710
TI  - Migrant Workers in Asia Pacific and Their Rights to Health.

PMID- 26294711
TI  - FVIII-VWF dos-a-dos.
AB  - In this issue of Blood, back-to-back (dos-a-dos) papers by Chiu et al and Yee et
      al present complementary findings of structural investigations into the
      interaction between factor VIII (FVIII) and von Willebrand factor (VWF). The
      binding of FVIII to VWF contributes in a major way to the regulation of
      hemostasis.

PMID- 26294712
TI  - Quantitative FDG-PET: a new biomarker in PMBCL.
AB  - In this issue of Blood, Ceriani et al introduce, in primary mediastinal B-cell
      lymphoma (PMBCL), a new prognostic factor measured on pretreatment 18F
      fluorodeoxyglucose (18FDG)-positron emission tomography (PET)/computed tomography
      (CT): the total lesion glycolysis (TLG), which is an index of the glucose uptake
      by the total tumor burden. This paper is part of the International Extranodal
      Lymphoma Study Group (IELSG) 26 prospective study designed to evaluate the role
      of PET in the treatment of PMBCL.

PMID- 26294713
TI  - Small clots with large impact.
AB  - In this issue of Blood, Kirstine Sogaard and colleagues report on the relevance
      of splanchnic vein thrombosis (SVT) as a marker of occult malignant disease.

PMID- 26294714
TI  - Engineered T cells can fight malignant T cells.
AB  - In this issue of Blood, Mamonkin and colleagues report genetically engineered T
      cells with specificity for the lineage marker CD5 selectively kill T-lymphoma but
      not normal T cells, although both express the CD5 target antigen.

PMID- 26294716
TI  - New mutation in hairy cell leukemia.
AB  - In this issue of Blood, Dietrich et al make the first observation of the presence
      of deleterious CDKN1B mutation in 16% of patients with hairy cell leukemia (HCL).
      Furthermore, in the majority of patients, the CDKN1B mutation was clonal,
      suggesting that this mutation plays a role in the pathogenesis of HCL.

PMID- 26294715
TI  - Dicing up T-ALL.
AB  - In this issue of Blood, Junker et al delineate a novel signaling axis involving
      miR-21 and the tumor suppressor Pdcd4 that is essential for Notch-mediated
      induction of T-cell acute lymphoblastic leukemia (T-ALL).

PMID- 26294717
TI  - Cladribine for mastocytosis: benefits and risks.
AB  - In this issue of Blood, Barete et al report the safety and efficacy of cladribine
      in 68 adult patients with mastocytosis.

PMID- 26294718
TI  - Platelet GPVI repairs its own damage.
AB  - In this issue of Blood, Gros et al report that glycoprotein VI (GPVI) promotes
      the proinflammatory role of platelets by increasing neutrophil secretion and
      toxicity while at the same time repairing the vascular damage inflicted by
      neutrophil activation, thereby maintaining vascular integrity. Significantly,
      this effect is independent of hemostasis.

PMID- 26294719
TI  - Prognostic relevance of MYD88 mutations in CLL: the jury is still out.

PMID- 26294720
TI  - The predictive strength of next-generation sequencing MRD detection for relapse
      compared with current methods in childhood ALL.

PMID- 26294722
TI  - Over 50 Years of Fibrinogen Concentrate.
AB  - March 2013 represented the 50th anniversary of the first license granted for a
      fibrinogen concentrate. In this review, we look at the history of bleeding
      management that led to the development of fibrinogen concentrate, discuss its
      current use, and consider future developments for this product. 

PMID- 26294723
TI  - A phase II multi-center trial of pentostatin plus cyclophosphamide with
      ofatumumab in older previously untreated chronic lymphocytic leukemia patients.

PMID- 26294724
TI  - CD14+ cells from peripheral blood positively regulate hematopoietic stem and
      progenitor cell survival resulting in increased erythroid yield.
AB  - Expansion of erythroblasts from human peripheral blood mononuclear cells is 4- to
      15-fold more efficient than that of CD34(+) cells purified from peripheral blood
      mononuclear cells. In addition, purified CD34(+) and CD34(-) populations from
      blood do not reconstitute this erythroid yield, suggesting a role for feeder
      cells present in blood mononuclear cells that increase hematopoietic output.
      Immunodepleting peripheral blood mononuclear cells for CD14(+) cells reduced
      hematopoietic stem and progenitor cell expansion. Conversely, the yield was
      increased upon co-culture of CD34(+) cells with CD14(+) cells (full contact or
      transwell assays) or CD34(+) cells re-constituted in conditioned medium from
      CD14(+) cells. In particular, CD14(++)CD16(+) intermediate monocytes/macrophages
      enhanced erythroblast outgrowth from CD34(+) cells. No effect of CD14(+) cells on
      erythroblasts themselves was observed. However, 2 days of co-culturing CD34(+)
      and CD14(+) cells increased CD34(+) cell numbers and colony-forming units 5-fold.
      Proliferation assays suggested that CD14(+) cells sustain CD34(+) cell survival
      but not proliferation. These data identify previously unrecognized erythroid and
      non-erythroid CD34(-) and CD34(+) populations in blood that contribute to the
      erythroid yield. A flow cytometry panel containing CD34/CD36 can be used to
      follow specific stages during CD34(+) differentiation to erythroblasts. We have
      shown modulation of hematopoietic stem and progenitor cell survival by CD14(+)
      cells present in peripheral blood mononuclear cells which can also be found near
      specific hematopoietic niches in the bone marrow.

PMID- 26294726
TI  - Growth differentiation factor 15 (GDF15) promotes osteoclast differentiation and
      inhibits osteoblast differentiation and high serum GDF15 levels are associated
      with multiple myeloma bone disease.

PMID- 26294725
TI  - Pediatric T-cell lymphoblastic leukemia evolves into relapse by clonal selection,
      acquisition of mutations and promoter hypomethylation.
AB  - Relapsed precursor T-cell acute lymphoblastic leukemia is characterized by
      resistance against chemotherapy and is frequently fatal. We aimed at
      understanding the molecular mechanisms resulting in relapse of T-cell acute
      lymphoblastic leukemia and analyzed 13 patients at first diagnosis, remission and
      relapse by whole exome sequencing, targeted ultra-deep sequencing, multiplex
      ligation dependent probe amplification and DNA methylation array. Compared to
      primary T-cell acute lymphoblastic leukemia, in relapse the number of single
      nucleotide variants and small insertions and deletions approximately doubled from
      11.5 to 26. Targeted ultra-deep sequencing sensitively detected subclones that
      were selected for in relapse. The mutational pattern defined two types of
      relapses. While both are characterized by selection of subclones and acquisition
      of novel mutations, 'type 1' relapse derives from the primary leukemia whereas
      'type 2' relapse originates from a common pre-leukemic ancestor. Relapse-specific
      changes included activation of the nucleotidase NT5C2 resulting in resistance to
      chemotherapy and mutations of epigenetic modulators, exemplified by SUZ12, WHSC1
      and SMARCA4. While mutations present in primary leukemia and in relapse were
      enriched for known drivers of leukemia, relapse-specific changes revealed an
      association with general cancer-promoting mechanisms. This study thus identifies
      mechanisms that drive progression of pediatric T-cell acute lymphoblastic
      leukemia to relapse and may explain the characteristic treatment resistance of
      this condition.

PMID- 26294727
TI  - Toll-like receptor stimulation in splenic marginal zone lymphoma can modulate
      cell signaling, activation and proliferation.
AB  - Recent studies on splenic marginal zone lymphoma identified distinct mutations in
      genes belonging to the B-cell receptor and Toll-like receptor signaling pathways,
      thus pointing to their potential implication in the biology of the disease.
      However, limited data is available regarding the exact role of TLRs. We aimed at
      characterizing the expression pattern of TLRs in splenic marginal zone lymphoma
      cells and their functional impact on the activation, proliferation and viability
      of malignant cells in vitro. Cells expressed significant levels of TLR1, TLR6,
      TLR7, TLR8, TLR9 and TLR10 mRNA; TLR2 and TLR4 showed a low, variable pattern of
      expression among patients whereas TLR3 and TLR5 mRNAs were undetectable; mRNA
      specific for TLR signaling molecules and adapters was also expressed. At the
      protein level, TLR1, TLR6, TLR7, TLR9 and TLR10 were detected. Stimulation of
      TLR1/2, TLR2/6 and TLR9 with their respective ligands triggered the activation of
      IRAK kinases, MAPK and NF-kappaB signaling pathways, and the induction of CD86
      and CD25 activation molecules, although in a heterogeneous manner among different
      patient samples. TLR-induced activation and cell viability were also inhibited by
      a specific IRAK1/4 inhibitor, thus strongly supporting the specific role of TLR
      signaling in these processes. Furthermore, TLR2/6 and TLR9 stimulation also
      significantly increased cell proliferation. In conclusion, we demonstrate that
      splenic marginal zone lymphoma cells are equipped with functional TLR and
      signaling molecules and that the stimulation of TLR1/2, TLR2/6 and TLR9 may play
      a role in regulating disease pathobiology, likely promoting the expansion of the
      neoplastic clone.

PMID- 26294728
TI  - Ligand-induced STAT3 signaling increases at relapse and is associated with
      outcome in pediatric acute myeloid leukemia: a report from the Children's
      Oncology Group.

PMID- 26294729
TI  - Competing risk survival analysis in patients with symptomatic Waldenstrom
      macroglobulinemia: the impact of disease unrelated mortality and of rituximab
      based primary therapy.

PMID- 26294730
TI  - Clinical profile and treatment outcome of older (>75 years) patients with
      systemic AL amyloidosis.
AB  - Systemic AL amyloidosis, a disease with improving outcomes using novel therapies,
      is increasingly recognized in the elderly but treatment and outcomes have not
      been systematically studied in this group of patients in whom comorbidities and
      frailty may compound morbidity and mortality. We report the outcomes of 295
      patients with systemic AL amyloidosis >=75 years seen at the UK National
      Amyloidosis Centre from 2005-2012. The median age was 78.5 years. The median
      overall survival was 20 months. Two hundred and thirty-eight patients received
      chemotherapy and 57 elected for supportive care only (overall survival - 24 and
      8.4 months, respectively). On intention-to-treat analysis, 44% achieved a
      hematologic response including a very good partial response or better in 23%. The
      median overall survival was 6.2 years in patients achieving very good partial
      response or better at the 6-month landmark analysis and 1.5 years in non
      responders. Factors independently indicating a poor prognosis were: cardiac
      involvement, performance status >=2; systolic blood pressure <100 mmHg and, on
      landmark analysis, achieving less than a very good partial response. Treatment of
      systemic AL amyloidosis in the elderly is challenging. Deep clonal responses are
      associated with excellent survival and organ responses. Achieving a response to
      the first-line regimen appears particularly important as outcomes of non
      responders are similar to those of untreated patients. Prospective trials with
      lower toxicity, outpatient treatment regimens are needed.

PMID- 26294731
TI  - Abnormal Hedgehog pathway in myelodysplastic syndrome and its impact on patients'
      outcome.

PMID- 26294732
TI  - Gene-expression and in vitro function of mesenchymal stromal cells are affected
      in juvenile myelomonocytic leukemia.
AB  - An aberrant interaction between hematopoietic stem cells and mesenchymal stromal
      cells has been linked to disease and shown to contribute to the pathophysiology
      of hematologic malignancies in murine models. Juvenile myelomonocytic leukemia is
      an aggressive malignant disease affecting young infants. Here we investigated the
      impact of juvenile myelomonocytic leukemia on mesenchymal stromal cells.
      Mesenchymal stromal cells were expanded from bone marrow samples of patients at
      diagnosis (n=9) and after hematopoietic stem cell transplantation (n=7; from 5
      patients) and from healthy children (n=10). Cells were characterized by
      phenotyping, differentiation, gene expression analysis (of controls and samples
      obtained at diagnosis) and in vitro functional studies assessing immunomodulation
      and hematopoietic support. Mesenchymal stromal cells from patients did not differ
      from controls in differentiation capacity nor did they differ in their capacity
      to support in vitro hematopoiesis. Deep-SAGE sequencing revealed differential
      mRNA expression in patient-derived samples, including genes encoding proteins
      involved in immunomodulation and cell-cell interaction. Selected gene expression
      normalized during remission after successful hematopoietic stem cell
      transplantation. Whereas natural killer cell activation and peripheral blood
      mononuclear cell proliferation were not differentially affected, the suppressive
      effect on monocyte to dendritic cell differentiation was increased by mesenchymal
      stromal cells obtained at diagnosis, but not at time of remission. This study
      shows that active juvenile myelomonocytic leukemia affects the immune response
      related gene expression and function of mesenchymal stromal cells. In contrast,
      the differential gene expression of hematopoiesis-related genes could not be
      supported by functional data. Decreased immune surveillance might contribute to
      the therapy resistance and progression in juvenile myelomonocytic leukemia.

PMID- 26294733
TI  - Homozygous knockout of the piezo1 gene in the zebrafish is not associated with
      anemia.

PMID- 26294735
TI  - Clinical profile associated with infections in patients with chronic lymphocytic
      leukemia. Protective role of immunoglobulin replacement therapy.

PMID- 26294734
TI  - Small-molecule nociceptin receptor agonist ameliorates mast cell activation and
      pain in sickle mice.
AB  - Treatment of pain with morphine and its congeners in sickle cell anemia is
      suboptimal, warranting the need for analgesics devoid of side effects, addiction
      and tolerance liability. Small-molecule nociceptin opioid receptor ligands show
      analgesic efficacy in acute and chronic pain models. We show that AT-200, a high
      affinity nociceptin opioid receptor agonist with low efficacy at the mu opioid
      receptor, ameliorated chronic and hypoxia/reoxygenation-induced mechanical,
      thermal and deep tissue/musculoskeletal hyperalgesia in HbSS-BERK sickle mice.
      The antinociceptive effect of AT-200 was antagonized by SB-612111, a nociceptin
      opioid receptor antagonist, but not naloxone, a non-selective mu opioid receptor
      antagonist. Daily 7-day treatment with AT-200 did not develop tolerance and
      showed a sustained anti-nociceptive effect, which improved over time and led to
      reduced plasma serum amyloid protein, neuropeptides, inflammatory cytokines and
      mast cell activation in the periphery. These data suggest that AT-200 ameliorates
      pain in sickle mice via the nociceptin opioid receptor by reducing inflammation
      and mast cell activation without causing tolerance. Thus, nociceptin opioid
      receptor agonists are promising drugs for treating pain in sickle cell anemia. 

PMID- 26294736
TI  - Mutated JAK kinases and deregulated STAT activity are potential therapeutic
      targets in cutaneous T-cell lymphoma.

PMID- 26294737
TI  - Assessing patients' anticoagulation preferences for the treatment of cancer
      associated thrombosis using conjoint methodology.
AB  - Low molecular weight heparins have demonstrated superiority over coumarins in the
      extended treatment of cancer-associated thrombosis and are recommended as first
      line therapy in clinical guidelines. Non-vitamin K oral antagonists are yet to be
      evaluated against low molecular weight heparin for this indication. Nevertheless,
      a perception that patients favor oral anticoagulants over injections may lead to
      an increased prescribing of warfarin or non-vitamin K oral antagonists despite
      the evidence gap. There has been no evaluation of cancer patient preferences for
      anticoagulants and whether such an evidence gap is an acceptable trade-off for
      patients prescribed orals. We conducted a study to assess what features are most
      important to CAT patients regarding their choice of anticoagulant. Two modules
      were applied: Initial in-depth interviews with 9 patients diagnosed with cancer
      associated thrombosis, and thereafter quantitative research, where a further 100
      patients completed a choice-based-conjoint exercise, where 15 different scenarios
      were presented to identify the most important attributes of an anticoagulant.
      Seventy percent of the patients were treated with injected medication (low
      molecular weight heparin) and 30% with oral medications. Patients most valued an
      anticoagulant with minimal interference with their cancer treatment (39%), low
      thrombosis recurrence rate (24%), and low risk of major bleed (19%). Preference
      for oral administration over injection had moderate importance (13%). The results
      show that patients prefer an anticoagulant that does not interfere with their
      cancer treatment, suggesting the primacy of the cancer disease over venous
      thromboembolism in these patients. Patients also favor efficacy and safety over
      convenience of route of administration.

PMID- 26294739
TI  - Working long hours is associated with higher risk of stroke, study shows.

PMID- 26294738
TI  - Karyotype evolution and acquisition of FLT3 or RAS pathway alterations drive
      progression of myelodysplastic syndrome to acute myeloid leukemia.

PMID- 26294740
TI  - Intralesional Vitamin D Injection May Be an Effective Treatment Option for Warts.
AB  - BACKGROUND: Plantar warts are typically resistant to treatment. In recent years,
      treatments have included administration of intralesional tuberculin; measles,
      mumps, rubella vaccine; and Candida albicans antigen immunotherapy. To the best
      of our knowledge, there are no reports of intralesional vitamin D administration
      for the treatment of warts. AIM: To evaluate the efficacy and safety of
      intralesional vitamin D treatment for plantar warts. METHODS: Twenty patients
      with single or multiple plantar warts were included in this study. Vitamin D(3)
      (0.2 mL, 7.5 mg/mL) was injected into the base of the warts after prilocaine (0.1
      mL, 20 mg/mL) injection. A maximum of 5 warts were treated in 1 session, with at
      maximum 2 injections performed at 4-week intervals. RESULTS: In total, 16 of 20
      patients (80%) showed complete resolution of warts, and 1 patient showed partial
      resolution. Three patients failed to show any response. No recurrence or serious
      adverse effects were observed. CONCLUSION: Intralesional vitamin D(3) may be an
      effective treatment option for warts.

PMID- 26294741
TI  - Antitumor Effects and Mechanisms of AZD4547 on FGFR2-Deregulated Endometrial
      Cancer Cells.
AB  - Uncontrolled activation of FGFRs induces the progression of various cancers. It
      was recently reported that FGFR2-activating mutants are implicated in about 12%
      of endometrial carcinomas. AZD4547, a potent pan-FGFR inhibitor, is currently
      being evaluated in clinical trials for several FGFR-driven cancers. However,
      AZD4547 has not been examined yet against FGFR2 mutant-driven endometrial
      cancers. Thus, we evaluated the activity of AZD4547 against four different
      endometrial cancer cells, including AN3-CA, MFE296, MFE280, and HEC1A, where all
      but HEC1A cells express distinctive FGFR2 mutations. We found that AZD4547
      exhibits potent antiproliferative activity (EC50 = 31 nmol/L) against AN3-CA
      cells harboring FGFR2-K310R/N550K mutant. Analysis using a phospho-kinase array
      revealed that AZD4547 blocks FGFR2 downstream signaling, such as p38, ERK1/2,
      JNK, p70S6K, and PLCgamma. Moreover, oral administration of AZD4547 (30 mg/kg,
      every day) remarkably delayed tumor growth in a mouse xenograft model of AN3-CA
      cells. Unbiased reporter gene assay showed that AZD4547 antagonizes the aFGF
      induced activation of several transcription factors, including EGR1, ELK-1/SRF,
      AP-1, and NFkappaB. Genome-wide transcriptome analysis revealed that AZD4547
      perturbs a number of transcriptions, and EGR1 was identified as one of the major
      targets of AZD4547. The significance of the FGFR2-EGR1 axis in endometrial cancer
      progression has not been reported. In addition, using kinome-wide inhibition
      profiling analysis, we first identified potential new target kinases of AZD4547,
      including MAP4K3, MAP4K5, IRR, RET, and FLT3. Our study demonstrated that AZD4547
      exhibits its therapeutic activity against endometrial cancer cells by perturbing
      various regulatory mechanisms related to FGFR signaling.

PMID- 26294742
TI  - Antibody Format and Drug Release Rate Determine the Therapeutic Activity of
      Noninternalizing Antibody-Drug Conjugates.
AB  - The development of antibody-drug conjugates (ADC), a promising class of
      anticancer agents, has traditionally relied on the use of antibodies capable of
      selective internalization in tumor cells. We have recently shown that also
      noninternalizing antibodies, coupled to cytotoxic drugs by means of disulfide
      linkers that can be cleaved in the tumor extracellular environment, can display a
      potent therapeutic activity. Here, we have compared the tumor-targeting
      properties, drug release rates, and therapeutic performance of two ADCs, based on
      the maytansinoid DM1 thiol drug and on the F8 antibody, directed against the
      alternatively spliced Extra Domain A (EDA) domain of fibronectin. The antibody
      was used in IgG or in small immune protein (SIP) format. In both cases, DM1 was
      coupled to unpaired cysteine residues, resulting in a drug-antibody ratio of 2.
      In biodistribution studies, SIP(F8)-SS-DM1 accumulated in the tumor and cleared
      from circulation more rapidly than IgG(F8)-SS-DM1. However, the ADC based on the
      IgG format exhibited a higher tumor uptake at later time points (e.g., 33%IA/g
      against 8%IA/g at 24 hours after intravenous administration). In mouse plasma,
      surprisingly, the ADC products in IgG format were substantially more stable
      compared with the SIP format (half-lives >48 hours and <3 hours at 37 degrees C,
      respectively), revealing a novel mechanism for the control of disulfide-based
      drug release rates. Therapy experiments in immunocompetent mice bearing murine F9
      tumors revealed that SIP(F8)-SS-DM1 was more efficacious than IgG(F8)-SS-DM1 when
      the two products were compared either in an equimolar basis or at equal milligram
      doses.

PMID- 26294743
TI  - Differences in Expression of Key DNA Damage Repair Genes after Epigenetic-Induced
      BRCAness Dictate Synthetic Lethality with PARP1 Inhibition.
AB  - The triple-negative breast cancer (TNBC) subtype represents a cancer that is
      highly aggressive with poor patient outcome. Current preclinical success has been
      gained through synthetic lethality, targeting genome instability with PARP
      inhibition in breast cancer cells that harbor silencing of the homologous
      recombination (HR) pathway. Histone deacetylase inhibitors (HDACi) are a class of
      drugs that mediate epigenetic changes in expression of HR pathway genes. Here, we
      compare the activity of the pan-HDAC inhibitor suberoylanilide hydroxamic acid
      (SAHA), the class I/IIa HDAC inhibitor valproic acid (VPA), and the HDAC1/2
      specific inhibitor romidepsin (ROMI) for their capability to regulate DNA damage
      repair gene expression and in sensitizing TNBC to PARPi. We found that two of the
      HDACis tested, SAHA and ROMI, but not VPA, indeed inhibit HR repair and that
      RAD51, BARD1, and FANCD2 represent key proteins whose inhibition is required for
      HDACi-mediated therapy with PARP inhibition in TNBC. We also observed that
      restoration of BRCA1 function stabilizes the genome compared with mutant BRCA1
      that results in enhanced polyploid population after combination treatment with
      HDACi and PARPi. Furthermore, we found that overexpression of the key HR protein
      RAD51 represents a mechanism for this resistance, promoting aberrant repair and
      the enhanced polyploidy observed. These findings highlight the key components of
      HR in guiding synthetic lethality with PARP inhibition and support the rationale
      for utilizing the novel combination of HDACi and PARPi against TNBC in the
      clinical setting.

PMID- 26294744
TI  - Integrating Image-Based High-Content Screening with Mouse Models Identifies 5
      Hydroxydecanoate as a Neuroprotective Drug for Paclitaxel-Induced Neuropathy.
AB  - Chemotherapy-induced neurotoxicity is a common adverse effect of cancer
      treatment. No medication has been shown to be effective in the prevention or
      treatment of chemotherapy-induced neurotoxicity. This study aimed to discover
      potential neuroprotective drugs for paclitaxel-induced neurotoxicity. An image
      based high-content platform was first developed to screen for potential
      neuroprotective drugs. The screening system comprised of automated image
      acquisition and multiparameter analysis, including neuronal viability, neurite
      outgrowth, and synaptogenesis. By this platform, we obtained a candidate list
      from compound libraries. In the drug screening from compound libraries of ion
      channel ligands, REDOX and GABAergic ligands, 5-hydroxydecanoate (5-HD) exhibited
      the most significant neuroprotective effects against paclitaxel-induced
      neurotoxicity in both cortical and dorsal root ganglion (DRG) neurons. In mouse
      behavioral tests, 5-HD restored the thermal sensitivity and alleviated mechanical
      allodynia induced by paclitaxel. Electron micrographs of sciatic nerve revealed
      that 5-HD reduced the damages caused by paclitaxel in the nonmyelinated and
      smaller myelinated fibers. The mechanistic study on DRG neurons suggested that 5
      HD rescued the dysregulation of intracellular calcium homeostasis provoked by
      paclitaxel. Importantly, 5-HD did not jeopardize the antitumor effect of
      paclitaxel in tumor xenograft models. In conclusion, we established an imaged
      based high-content screening platform and a protocol for verifying the
      neuroprotective effect in vivo, by which 5-HD was identified and validated as a
      potential neuroprotective drug for paclitaxel-induced neuropathy.

PMID- 26294745
TI  - A Novel Inhibitor of AKT1-PDPK1 Interaction Efficiently Suppresses the Activity
      of AKT Pathway and Restricts Tumor Growth In Vivo.
AB  - The serine/threonine kinase AKT/PKB has a critical role in the regulation of cell
      proliferation. Because AKT signaling is deregulated in numerous human
      malignancies, it has become an attractive anticancer drug target. A number of
      small molecule AKT kinase inhibitors have been developed; however, severe side
      effects have prevented their use in clinical trials. To find inhibitors of AKT1
      signaling with principally novel mechanism of action, we carried out a live cell
      based screen for small molecule inhibitors of physical interaction between AKT1
      and its primary activator PDPK1. The screen revealed one molecule-NSC156529,
      which downregulated AKT1 signaling, efficiently decreased the proliferation of
      human cancer cells in vitro, and substantially inhibited the growth of prostate
      tumor xenografts in vivo. Interestingly, the treated tumor xenografts exhibited
      higher expression level of normal prostate differentiation markers but did not
      show augmented cell death, suggesting that the identified compound primarily
      enhances the differentiation of malignant cells toward normal prostate epithelium
      and thus poses as an attractive lead compound for developing novel antitumor
      agents with less cytotoxic side effects.

PMID- 26294746
TI  - Archaic inheritance: supporting high-altitude life in Tibet.
AB  - The Tibetan Plateau, often called the roof of the world, sits at an average
      altitude exceeding 4,500 m. Because of its extreme altitude, the Plateau is one
      of the harshest human-inhabited environments in the world. This, however, did not
      impede human colonization, and the Tibetan people have made the Tibetan Plateau
      their home for many generations. Many studies have quantified their markedly
      different physiological response to altitude and proposed that Tibetans were
      genetically adapted. Recently, advances in sequencing technologies led to the
      discovery of a set of candidate genes which harbor mutations that are likely
      beneficial at high altitudes in Tibetans. Since then, other studies have further
      characterized this impressive adaptation. Here, in this minireview, we discuss
      the progress made since the discovery of the genes involved in Tibetans'
      adaptation to high altitude with a particular emphasis on describing the series
      of studies that led us to conclude that archaic human DNA likely contributed to
      this impressive adaptation.

PMID- 26294747
TI  - The cerebral venous system and hypoxia.
AB  - Most hypobaric hypoxia studies have focused on oxygen delivery and therefore
      cerebral blood inflow. Few have studied venous outflow. However, the volume of
      blood entering and leaving the skull (~700 ml/min) is considerably greater than
      cerebrospinal fluid production (0.35 ml/min) or edema formation rates and slight
      imbalances of in- and outflow have considerable effects on intracranial pressure.
      This dynamic phenomenon is not necessarily appreciated in the currently taught
      static "Monro-Kellie" doctrine, which forms the basis of the "Tight-Fit"
      hypothesis thought to underlie high altitude headache, acute mountain sickness,
      and high altitude cerebral edema. Investigating both sides of the cerebral
      circulation was an integral part of the 2007 Xtreme Everest Expedition. The
      results of the relevant studies performed as part of and subsequent to this
      expedition are reviewed here. The evidence from recent studies suggests a
      relative venous outflow insufficiency is an early step in the pathogenesis of
      high altitude headache. Translation of knowledge gained from high altitude
      studies is important. Many patients in a critical care environment develop
      hypoxemia akin to that of high altitude exposure. An inability to drain the
      hypoxemic induced increase in cerebral blood flow could be an underappreciated
      regulatory mechanism of intracranial pressure. 

PMID- 26294748
TI  - Pharmacology of acute mountain sickness: old drugs and newer thinking.
AB  - Pharmacotherapy in acute mountain sickness (AMS) for the past half century has
      largely rested on the use of carbonic anhydrase (CA) inhibitors, such as
      acetazolamide, and corticosteroids, such as dexamethasone. The benefits of CA
      inhibitors are thought to arise from their known ventilatory stimulation and
      resultant greater arterial oxygenation from inhibition of renal CA and generation
      of a mild metabolic acidosis. The benefits of corticosteroids include their broad
      based anti-inflammatory and anti-edemagenic effects. What has emerged from more
      recent work is the strong likelihood that drugs in both classes act on other
      pathways and signaling beyond their classical actions to prevent and treat AMS.
      For the CA inhibitors, these include reduction in aquaporin-mediated
      transmembrane water transport, anti-oxidant actions, vasodilation, and anti
      inflammatory effects. In the case of corticosteroids, these include protection
      against increases in vascular endothelial and blood-brain barrier permeability,
      suppression of inflammatory cytokines and reactive oxygen species production, and
      sympatholysis. The loci of action of both classes of drug include the brain, but
      may also involve the lung as revealed by benefits that arise with selective
      administration to the lungs by inhalation. Greater understanding of their
      pluripotent actions and sites of action in AMS may help guide development of
      better drugs with more selective action and fewer side effects. 

PMID- 26294749
TI  - Effect of hypertension and carotid occlusion on brain parenchymal arteriole
      structure and reactivity.
AB  - We studied the effect of hypertension and chronic hypoperfusion on brain
      parenchymal arteriole (PA) structure and function. PAs were studied isolated and
      pressurized from 18-wk-old Wistar-Kyoto (WKY18; n = 8) and spontaneously
      hypertensive stroke prone (SHRSP18; n = 8) and 5-wk-old prehypertensive (SHRSP5;
      n = 8) rats. In separate groups, unilateral common carotid artery occlusion
      (UCCAo) was performed for 4 wk to cause chronic hypoperfusion in 18-wk-old WKY
      (WKY18-CH; n = 8) and SHRSP (SHRSP18-CH; n = 8). UCCAo caused PAs to have
      significantly diminished myogenic tone (31 +/- 3 vs. 14 +/- 6% at 60 mmHg; P <
      0.05) and reactivity to pressure from WKY18-CH vs. WKY18 animals. The effect of
      UCCAo was limited to normotensive animals, as there was little effect of chronic
      hypoperfusion on vascular reactivity or percent tone in PAs from SHRSP18 vs.
      SHRSP18-CH animals (53 +/- 4 vs. 41 +/- 3%; P > 0.05). However, PAs from SHRSP18
      and SHRSP5 animals had significantly greater tone compared with WKY18, suggesting
      an effect of strain and not hypertension per se on PA vasoconstriction.
      Structurally, PAs from SHRSP18 and SHRSP5 animals had similar sized lumen
      diameters, but increased wall thickness and distensibility compared with WKY18.
      Interestingly, chronic hypoperfusion did not affect the structure of PAs from
      either WKY18-CH or SHRSP18-CH animals. Thus PAs responded to UCCAo with active
      vasodilation, but not structural remodeling, an effect that was absent in SHRSP.
      The increased tone of PAs from SHRSP animals, combined with lack of response to
      chronic hypoperfusion, may contribute to the propensity for ischemic lesions and
      increased perfusion deficit during hypertension. 

PMID- 26294751
TI  - Opposing effects of shear-mediated dilation and myogenic constriction on artery
      diameter in response to handgrip exercise in humans.
AB  - While the impact of changes in blood flow and shear stress on artery function are
      well documented, the acute effects of increases in arterial pressure are less
      well described in humans. The aim of this study was to assess the effect of 30
      min of elevated blood pressure, in the absence of changes in shear stress or
      sympathetic nervous system (SNS) activation, on conduit artery diameter. Ten
      healthy male subjects undertook three sessions of 30 min unilateral handgrip
      exercise at 5, 10, and 15% of maximal voluntary contractile (MVC) strength.
      Brachial artery shear rate and blood flow profiles were measured simultaneously
      during exercise in the active and contralateral resting arms. Bilateral brachial
      artery diameter was simultaneously assessed before and immediately postexercise.
      In a second experiment, six subjects repeated the 15% MVC condition while
      continuous vascular measurements were collected during muscle sympathetic nerve
      activity (MSNA) assessment using peroneal microneurography. We found that
      unilateral handgrip exercise at 5, 10, and 15% MVC strength induced stepwise
      elevations in blood pressure (P < 0.01, Deltamean arterial pressure: 7.06 +/-
      2.44, 8.50 +/- 2.80, and 18.35 +/- 3.52 mmHg, P < 0.01). Whereas stepwise
      increases were evident in shear rate in the exercising arm (P < 0.001), no
      changes were apparent in the nonexercising limb (P = 0.42). Brachial artery
      diameter increased in the exercising arm (P = 0.02), but significantly decreased
      in the nonexercising arm (P = 0.03). At 15% MVC, changes in diameter were
      significantly different between arms (interaction effect: P = 0.01), whereas this
      level of exertion produced no significant changes in MSNA. We conclude that acute
      increases in transmural pressure, independent of shear rate and changes in SNS
      activation, reduce arterial caliber in normotensive humans in vivo. These changes
      in diameter were mitigated by exercise-induced elevations in shear rate in the
      active limb. 

PMID- 26294752
TI  - Older people are no more likely to refuse cancer treatment than younger patients,
      survey finds.

PMID- 26294750
TI  - The effects of age and resistance loading on skeletal muscle ribosome biogenesis.
AB  - The hypertrophic response to resistance training is generally attenuated with
      aging; yet the mechanisms regulating this phenomenon are largely unknown. Several
      studies to date have shown blunted translational efficiency following acute
      resistance exercise in older adults; however, the effects on translational
      capacity (i.e., ribosome biogenesis) have not yet been examined. Thus the purpose
      of this study was to examine changes in markers of ribosome biogenesis following
      an acute bout of resistance loading (RL; 9 sets * 10 repetitions of knee
      extensions) in younger (Y; n = 14; 39.2 +/- 4.1 yr) and older (O; n = 12; 75.7 +/
      5.7 yr) adults. Vastus lateralis biopsies were taken pre- and 24 h post-RL, and
      muscle samples were analyzed for total RNA content, 45S pre-rRNA expression,
      ribosomal protein content, and levels of signaling proteins that regulate
      ribosome biogenesis. Before RL, O had higher total RNA content (+28%; P < 0.05),
      a trend toward higher 45S pre-rRNA expression (+59%; P = 0.08), and greater
      protein content of several ribosomal components (~ +50-80%; P < 0.05) than Y.
      However, 24 h post-RL, only Y increased 45S pre-rRNA expression (+34%; P < 0.01),
      possibly driven by higher basal p-Rb (Ser780) (+61%; P = 0.10), and a robust
      transcription initiation factor (TIF)-1a response (+75%; P < 0.05). RL tended to
      increase protein components of the 40S ribosomal subunit in Y only (~ +20-25%; P
      <= 0.12). Overall, the data suggest blunted ribosome biogenesis in response to RL
      in O, which may be a potential mechanism driving the age-related attenuation of
      resistance training-induced hypertrophy. 

PMID- 26294753
TI  - Fear Biases in Emotional Face Processing Following Childhood Trauma as a Marker
      of Resilience and Vulnerability to Depression.
AB  - There is a high prevalence of depression in adults with a history of childhood
      maltreatment. A negative cognitive bias is implicated in the etiology of
      depressive symptomatology and has also been found in physically abused children
      who show preferential processing of anger. However, how these biases mediate the
      link between childhood maltreatment and adult depression has not yet been
      clarified. This study involved 36 patients with depression (19 with and 17
      without a history of childhood maltreatment) and 40 healthy controls (18 with and
      22 without a history of childhood maltreatment). All participants were assessed
      using a facial emotion recognition task. Healthy individuals with a history of
      childhood maltreatment made significantly more errors in recognizing fear than
      anger. This difference between the number of errors for fear and anger was higher
      in healthy abused individuals than healthy nonabused individuals and depressed
      abused individuals. Resilient individuals with a history of childhood
      maltreatment but who have not developed depression show absence of a fear bias,
      which may help explain why they do not manifest depressive symptoms, despite
      their experiences of childhood maltreatment. In contrast, other individuals who
      become vulnerable to depression after childhood maltreatment show an amplified
      bias toward fear. 

PMID- 26294754
TI  - Implementing Comprehensive School Health in Alberta, Canada: the principal's
      role.
AB  - Comprehensive School Health (CSH) is an internationally recognized framework that
      moves beyond the individual to holistically address school health, leading to the
      development of health-enhancing behaviors while also improving educational
      outcomes. Previous research has suggested that principal support for CSH
      implementation is essential, but this role has yet to be explored. Therefore, the
      purpose of this research was to examine the role of the principal in the
      implementation of a CSH project aimed at creating a healthy school culture. This
      research was guided by the grounded ethnography method. Semi-structured
      interviews were conducted with APPLE School principals (n = 29) to qualitatively
      explore their role in creating a healthy school culture. A model consisting of
      five major themes emerged, suggesting that the principal played a fluid role
      throughout the CSH implementation process. Principals (i) primed the cultural
      change; (ii) communicated the project's importance to others; (iii) negotiated
      concerns and collaboratively planned; (iv) held others accountable to the change,
      while enabling them to take ownership and (v) played an underlying supportive
      role, providing positive recognition and establishing ongoing commitment. This
      research provides recommendations to help establish effective leadership
      practices in schools, conducive to creating a healthy school culture.

PMID- 26294755
TI  - Health promoting leadership practices in four Norwegian industries.
AB  - The aim of this article is to address health promoting leadership; what do
      leaders actually do to promote health at work? Leadership practice plays a
      crucial role in the workplace and greatly affects the working environment and
      working conditions. Through a theoretical and empirical approach, we seek to find
      characteristics/patterns of health promoting leadership. The definition of health
      promoting leadership is a democratic and supportive leadership style, where
      leaders seek to motivate and inspire their employees. The study in this article
      is based on qualitative research methods. We have investigated and compared
      leadership practice in four different organizations/industries in Norway:
      construction, oil and gas, health care and cleaning. These organizations and
      professions are quite different, and thus leadership must be understood and
      developed within its context. However, we found some generic characteristics of
      health promoting leadership: hands-on, accessible, supportive, inclusive and
      democratic. Current literature only rarely addresses how leadership affects
      health promotion at work. Consequently, more knowledge is needed about how
      leaders really succeed in creating healthy workplaces and healthy employees.

PMID- 26294756
TI  - Thermal Degradation of Synthetic Cathinones: Implications for Forensic
      Toxicology.
AB  - The synthetic cathinones represent an important class of designer drugs. The
      widespread attention and publicity associated with these psychostimulants have
      resulted in numerous legislative actions at state and federal levels throughout
      the USA. These amphetamine-like compounds are characterized by a beta-keto
      functional group. Although the synthetic cathinones share many properties of
      their phenethylamine counterparts, the presence of the ketone moiety is
      responsible for a number of unique and distinct differences in terms of their
      chemical characteristics and properties. Thermal degradation of methcathinone was
      first reported several decades ago but has received limited attention. In this
      study, we identified in situ thermal degradation products for 18 cathinones
      during gas chromatography-mass spectrometry (GC-MS) analysis. Oxidative
      degradation arises from the loss of two hydrogens, yielding a characteristic 2 Da
      mass shift. Degradation products were characterized by prominent iminium base
      peaks with mass-to-charge ratios 2 Da lower than the parent drug, and in the case
      of the pyrrolidine-containing cathinones, prominent molecular ions arising from
      the 2,3-enamine. Chromatographic and mass spectroscopic data are described for 4
      ethylmethcathinone, 4-methylethcathinone, buphedrone, butylone, ethcathinone,
      ethylone, flephedrone, 3,4-methylenedioxy-alpha-pyrrolidinobutiophenone, 3,4
      methylenedioxypyrovalerone, mephedrone, methcathinone, methedrone, methylone, 4
      methyl-alpha-pyrrolidinobutiophenone, naphyrone, pentedrone, pentylone and
      pyrovalerone. Degradation was minimized by lowering injection temperatures,
      residence time in the inlet and eliminating active sites during chromatographic
      analysis. Chromatographic and mass spectral data for the cathinone degradation
      products are presented and discussed within the context of forensic toxicological
      analysis, selection of appropriate instrumental methods and implications for the
      interpretation of results. 

PMID- 26294757
TI  - Would judicial consent for assisted dying protect vulnerable people?

PMID- 26294758
TI  - Mental capacity as a safeguard in assisted dying: clarity is needed.

PMID- 26294759
TI  - 45,X/46,XY Mosaicism and Possible Association With Hypothyroidism in Males.
AB  - Mosaicism has a wide phenotypic spectrum but frequently manifests as the normal
      male phenotype. Its association with short stature has been well recognized and
      appears to respond effectively to growth hormone therapy. We present 2
      phenotypically normal males who both initially presented with short stature and
      were found to have hypothyroidism. They were treated for hypothyroidism but their
      growth did not improve as expected. Further testing revealed 45,X/46,XY mosaicism
      in both males. We propose that a potential link exists between 45,X/46,XY
      mosaicism and hypothyroidism, which has not been previously described in the
      literature. Furthermore, it may be beneficial to evaluate for other disorders
      such as 45,X/46,XY mosaicism in young males with short stature and hypothyroidism
      if their growth does not improve once they become euthyroid. 

PMID- 26294760
TI  - Late ELISA Testing in Infants Born to HIV-Positive Mothers.
AB  - We present the case of a young boy who was born to a human immunodeficiency virus
      (HIV)-positive mother and originally found to be uninfected. Evidence-based
      guidelines were followed regarding the mother's prenatal and infant's postnatal
      care, including the avoidance of breast milk. HIV DNA polymerase chain reaction
      qualitative tests were obtained at birth, 6 weeks and 4 months, and were all
      negative. He also received 6 weeks of prophylactic zidovudine. Despite these
      measures, his health began to decline at 17 months of age and antibody and
      serology tests performed at this time confirmed HIV infection. Guidelines no
      longer recommend routine antibody testing at 18 months of age to confirm the
      absence of infection in exposed infants with a record of negative virology in the
      first year of life. Based on this case and others we propose that this test be
      added back to the national guidelines for the early detection and prompt
      treatment of HIV infection in infants born to HIV-positive mothers. 

PMID- 26294761
TI  - Effect of "Pink Eye" Label on Parents' Intent to Use Antibiotics and Perceived
      Contagiousness.
AB  - Parents of children who presented for a pediatrics appointment responded to a
      clinical vignette that described a child with symptoms consistent with acute
      viral conjunctivitis. In a 2 * 2 randomized survey design, the physician in the
      vignette either used the term "pink eye" or "eye infection" to describe the
      symptoms, and either told parents that antibiotics are likely ineffective at
      treating the symptoms or did not discuss effectiveness. When the symptoms were
      referred to as "pink eye," parents remained interested in antibiotics, despite
      being informed about their ineffectiveness. By contrast, when the symptoms were
      referred to as an "eye infection," information about antibiotic ineffectiveness
      significantly reduced interest, Mdiff = 1.63, P < .001. Parents who received the
      "pink eye" label also thought that the symptoms were more contagious and were
      less likely to believe that their child could go to child care, compared with
      parents who received the "eye infection" label, Mdiff = 0.37, P = .38.

PMID- 26294762
TI  - Impaired dNTPase activity of SAMHD1 by phosphomimetic mutation of Thr-592.
AB  - SAMHD1 is a cellular protein that plays key roles in HIV-1 restriction and
      regulation of cellular dNTP levels. Mutations in SAMHD1 are also implicated in
      the pathogenesis of chronic lymphocytic leukemia and Aicardi-Goutieres syndrome.
      The anti-HIV-1 activity of SAMHD1 is negatively modulated by phosphorylation at
      residue Thr-592. The mechanism underlying the effect of phosphorylation on anti
      HIV-1 activity remains unclear. SAMHD1 forms tetramers that possess
      deoxyribonucleotide triphosphate triphosphohydrolase (dNTPase) activity, which is
      allosterically controlled by the combined action of GTP and all four dNTPs. Here
      we demonstrate that the phosphomimetic mutation T592E reduces the stability of
      the SAMHD1 tetramer and the dNTPase activity of the enzyme. To better understand
      the underlying mechanisms, we determined the crystal structures of SAMHD1
      variants T592E and T592V. Although the neutral substitution T592V does not
      perturb the structure, the charged T592E induces large conformational changes,
      likely triggered by electrostatic repulsion from a distinct negatively charged
      environment surrounding Thr-592. The phosphomimetic mutation results in a
      significant decrease in the population of active SAMHD1 tetramers, and hence the
      dNTPase activity is substantially decreased. These results provide a mechanistic
      understanding of how SAMHD1 phosphorylation at residue Thr-592 may modulate its
      cellular and antiviral functions. 

PMID- 26294763
TI  - Recapitulating the Structural Evolution of Redox Regulation in Adenosine 5'
      Phosphosulfate Kinase from Cyanobacteria to Plants.
AB  - In plants, adenosine 5'-phosphosulfate (APS) kinase (APSK) is required for
      reproductive viability and the production of 3'-phosphoadenosine 5'
      phosphosulfate (PAPS) as a sulfur donor in specialized metabolism. Previous
      studies of the APSK from Arabidopsis thaliana (AtAPSK) identified a regulatory
      disulfide bond formed between the N-terminal domain (NTD) and a cysteine on the
      core scaffold. This thiol switch is unique to mosses, gymnosperms, and
      angiosperms. To understand the structural evolution of redox control of APSK, we
      investigated the redox-insensitive APSK from the cyanobacterium Synechocystis sp.
      PCC 6803 (SynAPSK). Crystallographic analysis of SynAPSK in complex with either
      APS and a non-hydrolyzable ATP analog or APS and sulfate revealed the overall
      structure of the enzyme, which lacks the NTD found in homologs from mosses and
      plants. A series of engineered SynAPSK variants reconstructed the structural
      evolution of the plant APSK. Biochemical analyses of SynAPSK, SynAPSK H23C
      mutant, SynAPSK fused to the AtAPSK NTD, and the fusion protein with the H23C
      mutation showed that the addition of the NTD and cysteines recapitulated thiol
      based regulation. These results reveal the molecular basis for structural changes
      leading to the evolution of redox control of APSK in the green lineage from
      cyanobacteria to plants.

PMID- 26294764
TI  - Two-step Ligand Binding in a (betaalpha)8 Barrel Enzyme: SUBSTRATE-BOUND
      STRUCTURES SHED NEW LIGHT ON THE CATALYTIC CYCLE OF HisA.
AB  - HisA is a (betaalpha)8 barrel enzyme that catalyzes the Amadori rearrangement of
      N'-[(5'-phosphoribosyl)formimino]-5-aminoimidazole-4-carboxamide ribonucleotide
      (ProFAR) to N'-((5'-phosphoribulosyl) formimino)-5-aminoimidazole-4-carboxamide
      ribonucleotide (PRFAR) in the histidine biosynthesis pathway, and it is a
      paradigm for the study of enzyme evolution. Still, its exact catalytic mechanism
      has remained unclear. Here, we present crystal structures of wild type Salmonella
      enterica HisA (SeHisA) in its apo-state and of mutants D7N and D7N/D176A in
      complex with two different conformations of the labile substrate ProFAR, which
      was structurally visualized for the first time. Site-directed mutagenesis and
      kinetics demonstrated that Asp-7 acts as the catalytic base, and Asp-176 acts as
      the catalytic acid. The SeHisA structures with ProFAR display two different
      states of the long loops on the catalytic face of the structure and demonstrate
      that initial binding of ProFAR to the active site is independent of loop
      interactions. When the long loops enclose the substrate, ProFAR adopts an
      extended conformation where its non-reacting half is in a product-like
      conformation. This change is associated with shifts in a hydrogen bond network
      including His-47, Asp-129, Thr-171, and Ser-202, all shown to be functionally
      important. The closed conformation structure is highly similar to the
      bifunctional HisA homologue PriA in complex with PRFAR, thus proving that
      structure and mechanism are conserved between HisA and PriA. This study clarifies
      the mechanistic cycle of HisA and provides a striking example of how an enzyme
      and its substrate can undergo coordinated conformational changes before
      catalysis.

PMID- 26294765
TI  - Structure of the Legionella Effector, lpg1496, Suggests a Role in Nucleotide
      Metabolism.
AB  - Pathogenic Gram-negative bacteria use specialized secretion systems that
      translocate bacterial proteins, termed effectors, directly into host cells where
      they interact with host proteins and biochemical processes for the benefit of the
      pathogen. lpg1496 is a previously uncharacterized effector of Legionella
      pneumophila, the causative agent of Legionnaires disease. Here, we crystallized
      three nucleotide binding domains from lpg1496. The C-terminal domain, which is
      conserved among the SidE family of effectors, is formed of two largely alpha
      helical lobes with a nucleotide binding cleft. A structural homology search has
      shown similarity to phosphodiesterases involved in cleavage of cyclic
      nucleotides. We have also crystallized a novel domain that occurs twice in the N
      terminal half of the protein that we term the KLAMP domain due to the presence of
      homologous domains in bacterial histidine kinase-like ATP binding region
      containing proteins and S-adenosylmethionine-dependent methyltransferase
      proteins. Both KLAMP structures are very similar but selectively bind 3',5'-cAMP
      and ADP. A co-crystal of the KLAMP1 domain with 3',5'-cAMP reveals the
      contribution of Tyr-61 and Tyr-69 that produces pi-stacking interactions with the
      adenine ring of the nucleotide. Our study provides the first structural insights
      into two novel nucleotide binding domains associated with bacterial virulence.

PMID- 26294766
TI  - MEF2D deficiency in neonatal cardiomyocytes triggers cell cycle re-entry and
      programmed cell death in vitro.
AB  - The cardiomyocyte cell cycle is a poorly understood process. Mammalian
      cardiomyocytes permanently withdraw from the cell cycle shortly after birth but
      can re-enter the cell cycle and proliferate when subjected to injury within a
      brief temporal window in the neonatal period. Thus, investigating the mechanisms
      of cell cycle regulation in neonatal cardiomyocytes may provide critical insight
      into the molecular events that prevent adult myocytes from proliferating in
      response to injury or stress. MEF2D is a key transcriptional mediator of
      pathological remodeling in the adult heart downstream of various stress-promoting
      insults. However, the specific gene programs regulated by MEF2D in cardiomyocytes
      are unknown. By performing genome-wide transcriptome analysis using MEF2D
      depleted neonatal cardiomyocytes, we found a significant impairment in the cell
      cycle, characterized by the up-regulation of numerous positive cell cycle
      regulators. Expression of Pten, the primary negative regulator of PI3K/Akt, was
      significantly reduced in MEF2D-deficient cardiomyocytes and found to be a direct
      target gene of MEF2D. Consistent with these findings mutant cardiomyocytes showed
      activation of the PI3K/Akt survival pathway. Paradoxically, prolonged deficiency
      of MEF2D in neonatal cardiomyocytes did not trigger proliferation but instead
      resulted in programmed cell death, which is likely mediated by the E2F
      transcription factor. These results demonstrate a critical role for MEF2D in cell
      cycle regulation of post-mitotic, neonatal cardiomyocytes in vitro. 

PMID- 26294768
TI  - AGXT2L1 is down-regulated in heptocellular carcinoma and associated with abnormal
      lipogenesis.
AB  - AIMS: To clarify the clinical implications and functional role of the alanine
      glyoxylate aminotransferase 2-like 1 (AGXT2L1) gene in hepatocellular carcinoma
      (HCC). METHODS AND RESULTS: We confirmed that AGXT2L1 was down-regulated in liver
      cancer samples by immunohistochemical (IHC) staining. We also demonstrated that
      this down-regulation was associated with several clinicopathological features
      such as alpha fetoprotein (AFP) serum level and T stage. Furthermore, we showed
      with Kaplan-Meier analysis that expression of AGXT2L1 in tumour samples was
      significantly correlated with patient prognosis. The bioinformatic tool indicated
      that AGXT2L1 plays a role in the lipid metabolic process of HCC tissue, while
      siRNA silenced the expression of AGXT2L1 in HCC 97H and LM3 cells, confirming
      that down-regulation of AGXT2L1 promotes the lipogenesis of cancer cells.
      CONCLUSIONS: For the first time, we have shown that AGXT2L1 is down-regulated in
      HCC and its low expression indicates a poor prognosis. Our findings also
      demonstrated that AGXT2L1 is a crucial gene in the abnormal lipogenesis of HCC
      tissue.

PMID- 26294767
TI  - The Plasma Membrane Calcium Pump in Pancreatic Cancer Cells Exhibiting the
      Warburg Effect Relies on Glycolytic ATP.
AB  - Evidence suggests that the plasma membrane Ca(2+)-ATPase (PMCA), which is
      critical for maintaining a low intracellular Ca(2+) concentration ([Ca(2+)]i),
      utilizes glycolytically derived ATP in pancreatic ductal adenocarcinoma (PDAC)
      and that inhibition of glycolysis in PDAC cell lines results in ATP depletion,
      PMCA inhibition, and an irreversible [Ca(2+)]i overload. We explored whether this
      is a specific weakness of highly glycolytic PDAC by shifting PDAC cell (MIA PaCa
      2 and PANC-1) metabolism from a highly glycolytic phenotype toward mitochondrial
      metabolism and assessing the effects of mitochondrial versus glycolytic
      inhibitors on ATP depletion, PMCA inhibition, and [Ca(2+)]i overload. The highly
      glycolytic phenotype of these cells was first reversed by depriving MIA PaCa-2
      and PANC-1 cells of glucose and supplementing with alpha-ketoisocaproate or
      galactose. These culture conditions resulted in a significant decrease in both
      glycolytic flux and proliferation rate, and conferred resistance to ATP depletion
      by glycolytic inhibition while sensitizing cells to mitochondrial inhibition.
      Moreover, in direct contrast to cells exhibiting a high glycolytic rate,
      glycolytic inhibition had no effect on PMCA activity and resting [Ca(2+)]i in
      alpha-ketoisocaproate- and galactose-cultured cells, suggesting that the
      glycolytic dependence of the PMCA is a specific vulnerability of PDAC cells
      exhibiting the Warburg phenotype.

PMID- 26294769
TI  - Socioeconomic gradient in work disability in diabetes: evidence from three
      occupational cohorts.
AB  - BACKGROUND: The role of socioeconomic status in work disability among employees
      with diabetes is not well known. We examined the association between
      socioeconomic status and work disability among employees with and without
      diabetes taking into account comorbid conditions. METHODS: We used individual
      participant data from three occupational cohorts from Finland, France and the UK
      (employees with diabetes, n=2170, age-matched and sex-matched controls without
      diabetes, n=4340). In all cohorts, survey data were linked with register data and
      the employees were followed up on average for 4.4 years. Socioeconomic status was
      based on occupational titles. Work disability (sickness absence and disability
      pension) was indexed as the numbers of disability days and episodes. The study
      specific estimates were pooled using meta-analysis and effect modifications were
      studied with meta-regression. RESULTS: The average numbers of disability days and
      episodes per year were 1.5-3.5 times higher for persons with diabetes compared to
      those without. Among persons with diabetes, the risk of work disability was
      almost four times higher in the lowest compared to the highest occupational
      position (relative index of inequality (RII) for days 3.82; 95% CI 2.77 to 5.56;
      RII for episodes 3.80; 95% CI 3.13 to 4.61). This association was consistent in
      both sexes and regardless of comorbid conditions. In relative terms, the
      association of socioeconomic status and work disability was similar among those
      free of diabetes. CONCLUSIONS: A strong socioeconomic gradient in work disability
      was observed among people with and without diabetes.

PMID- 26294770
TI  - Widening inequalities in self-rated health by material deprivation? A trend
      analysis between 2001 and 2011 in Germany.
AB  - BACKGROUND: Research on inequalities in health has shown a strong association
      between the lack of standard of living (defined as material deprivation) and self
      rated health (SRH). In this study, we sought to further examine this association
      in a trend analysis of relative and absolute inequalities in SRH as defined by
      material deprivation in Germany. METHODS: Data were obtained from the German
      Socio-Economic Panel (GSOEP) between 2001 and 2011. Material deprivation was
      measured on the basis of 11 living standard items missing due to financial
      reasons. We used the relative index of inequality (RII) and slope index of
      inequality (SII) to measure inequalities in SRH by material deprivation,
      calculating pooled interval logistic regression with robust SEs. Stepwise models
      were estimated, including demographic and socioeconomic variables, to assess
      their inter-relation with inequalities in SRH by material deprivation. RESULTS:
      The results showed a steady increase in poor SRH over the 10-year duration of the
      study. A quadratic (inverted U-shaped) trend was observed in material deprivation
      in the standards of living, which rose from 2001 to 2005, and then declined in
      2011. A similar but non-significant trend was found in relative and absolute
      inequalities in SRH by material deprivation, which increased from 2001 to 2005
      and then declined. CONCLUSIONS: Inequality in SRH by material deprivation was
      relatively stable; however, an observed quadratic trend coincided with active and
      passive labour market reforms in Germany in early 2005.

PMID- 26294772
TI  - Clinical Utility of SMBG: Recommendations on the Use and Reporting of SMBG in
      Clinical Research.

PMID- 26294773
TI  - Trevor Orchard: Fruitful Contributions to Diabetes Epidemiology.

PMID- 26294774
TI  - Euglycemic Diabetic Ketoacidosis: A Predictable, Detectable, and Preventable
      Safety Concern With SGLT2 Inhibitors.

PMID- 26294775
TI  - Alcohol Consumption and the Risk of Type 2 Diabetes: A Systematic Review and Dose
      Response Meta-analysis of More Than 1.9 Million Individuals From 38 Observational
      Studies.
AB  - OBJECTIVE: Observational studies indicate that moderate levels of alcohol
      consumption may reduce the risk of type 2 diabetes. In addition to providing an
      updated summary of the existing literature, this meta-analysis explored whether
      reductions in risk may be the product of misclassification bias. RESEARCH DESIGN
      AND METHODS: A systematic search was undertaken, identifying studies that
      reported a temporal association between alcohol consumption and the risk of type
      2 diabetes. No restrictions were placed upon the language or date of publication.
      Non-English publications were, where necessary, translated using online
      translation tools. Models were constructed using fractional polynomial regression
      to determine the best-fitting dose-response relationship between alcohol intake
      and type 2 diabetes, with a priori testing of sex and referent group
      interactions. RESULTS: Thirty-eight studies met the selection criteria,
      representing 1,902,605 participants and 125,926 cases of type 2 diabetes. A
      conventional noncurrent drinking category was reported by 33 studies, while five
      reported a never-drinking category. Relative to combined abstainers, reductions
      in the risk of type 2 diabetes were present at all levels of alcohol intake <63
      g/day, with risks increasing above this threshold. Peak risk reduction was
      present between 10-14 g/day at an 18% decrease in hazards. Stratification of
      available data revealed that reductions in risk may be specific to women only and
      absent in studies that adopted a never-drinking abstention category or sampled an
      Asian population region. CONCLUSIONS: Reductions in risk among moderate alcohol
      drinkers may be confined to women and non-Asian populations. Although based on a
      minority of studies, there is also the possibility that reductions in risk may
      have been overestimated by studies using a referent group contaminated by less
      healthy former drinkers.

PMID- 26294776
TI  - Erratum. Predictive Low-Glucose Insulin Suspension Reduces Duration of Nocturnal
      Hypoglycemia in Children Without Increasing Ketosis. Diabetes Care 2015;38:1197
      1204.

PMID- 26294778
TI  - Comment on Inzucchi et al. Management of Hyperglycemia in Type 2 Diabetes, 2015:
      A Patient-Centered Approach. Update to a Position Statement of the American
      Diabetes Association and the European Association for the Study of Diabetes.
      Diabetes Care 2015;38:140-149.

PMID- 26294779
TI  - Response to Comment on Inzucchi et al. Management of Hyperglycemia in Type 2
      Diabetes, 2015: A Patient-Centered Approach. Update to a Position Statement of
      the American Diabetes Association and the European Association for the Study of
      Diabetes. Diabetes Care 2015;38:140-149.

PMID- 26294780
TI  - Comment on Tone et al. Six-Week Versus Twelve-Week Antibiotic Therapy for
      Nonsurgically Treated Diabetic Foot Osteomyelitis: A Multicenter Open-Label
      Controlled Randomized Study. Diabetes Care 2015;38:302-307.

PMID- 26294781
TI  - Response to Comment on Tone et al. Six-Week Versus Twelve-Week Antibiotic Therapy
      for Nonsurgically Treated Diabetic Foot Osteomyelitis: A Multicenter Open-Label
      Controlled Randomized Study. Diabetes Care 2015;38:302-307.

PMID- 26294782
TI  - Comment on Anjana et al. Incidence of Diabetes and Prediabetes and Predictors of
      Progression Among Asian Indians: 10-Year Follow-up of the Chennai Urban Rural
      Epidemiology Study (CURES). Diabetes Care 2015;38:1441-1448.

PMID- 26294783
TI  - Response to Comment on Anjana et al. Incidence of Diabetes and Prediabetes and
      Predictors of Progression Among Asian Indians: 10-Year Follow-up of the Chennai
      Urban Rural Epidemiology Study (CURES). Diabetes Care 2015;38:1441-1448.

PMID- 26294784
TI  - Comment on Tang et al. Effects of Insulin Glargine and Liraglutide Therapy on
      Liver Fat as Measured by Magnetic Resonance in Patients With Type 2 Diabetes: A
      Randomized Trial. Diabetes Care 2015;38:1339-1346.

PMID- 26294785
TI  - Response to Comment on Tang et al. Effects of Insulin Glargine and Liraglutide
      Therapy on Liver Fat as Measured by Magnetic Resonance in Patients With Type 2
      Diabetes: A Randomized Trial. Diabetes Care 2015;38:1339-1346.

PMID- 26294786
TI  - Antivirals in combination with corticosteroids compared to corticosteroids alone
      improve facial recovery in severe Bell's palsy... and possibly more?

PMID- 26294787
TI  - Short-course antimicrobial therapy may be clinically similar to a longer course
      for complicated intra-abdominal infections.

PMID- 26294788
TI  - Directly observed treatment is not the only solution for poor adherence and low
      cure of tuberculosis.

PMID- 26294791
TI  - Antiageing concepts and cardiovascular disease.

PMID- 26294789
TI  - European Evidence-based Consensus: Inflammatory Bowel Disease and Malignancies.

PMID- 26294790
TI  - Association of growth differentiation factor 11/8, putative anti-ageing factor,
      with cardiovascular outcomes and overall mortality in humans: analysis of the
      Heart and Soul and HUNT3 cohorts.
AB  - AIMS: Growth differentiation factor 11 and/or its homologue growth
      differentiation factor 8 (GDF11/8) reverses age-related cardiac hypertrophy and
      vascular ageing in mice. We investigated whether GDF11/8 associates with
      cardiovascular outcomes, left ventricular hypertrophy (LVH), or age in humans.
      METHODS AND RESULTS: We measured plasma GDF11/8 levels in 928 participants with
      stable ischaemic heart disease in the Heart and Soul study. We adjudicated heart
      failure hospitalization, stroke, myocardial infarction, death, and their
      composite endpoint. Left ventricular hypertrophy was evaluated by
      echocardiography. We used multivariable Cox proportional hazards models to
      compare rates of cardiovascular events and death across GDF11/8 quartiles and
      logistic regression models to evaluate the association between GDF11/8 and LVH.
      Four hundred and fifty participants (48.5%) experienced a cardiovascular event or
      death during 8.9 years of follow-up. The adjusted risk of the composite endpoint
      was lower in the highest compared with the lowest GDF11/8 quartile [hazard ratio
      (HR), 0.45; 95% confidence interval (CI), 0.33-0.60; P < 0.001]. We replicated
      this relationship of GDF11/8 to adverse events in 971 participants in the HUNT3
      cohort (adjusted HR, 0.34; 95% CI, 0.23-0.51; P < 0.001). Left ventricular
      hypertrophy was present in 368 participants (39.7%) at baseline. Participants in
      the highest quartile of GDF11/8 were less likely to have LVH than those in the
      lowest quartile (adjusted OR, 0.55; 95% CI, 0.35-0.86; P = 0.009). GDF11/8 levels
      were lower in older individuals (P < 0.001). CONCLUSION: In patients with stable
      ischaemic heart disease, higher GDF11/8 levels are associated with lower risk of
      cardiovascular events and death. Our findings suggest that GDF11/8 has similar
      cardioprotective properties in humans to those demonstrated in mice.

PMID- 26294792
TI  - Intrathoracic vertical overhanging approach for placement of an endo-stapler
      during single-port video-assisted thoracoscopic lobectomy?.
AB  - Single-port video-assisted thoracoscopic lobectomy is still difficult for most
      thoracic surgeons. Placement of an endo-stapler is one of the key issues when
      handling the bronchus or pulmonary vessels through one incision, especially if it
      would interfere with the traction belt. Therefore, we developed a novel method
      with an intrathoracic vertical overhanging approach to make the placement of the
      endo-stapler easier during single-port video-assisted thoracoscopic surgery
      lobectomy, and share our experience in this paper. 

PMID- 26294793
TI  - Biomarkers of iron metabolism are independently associated with impaired glucose
      metabolism and type 2 diabetes: the KORA F4 study.
AB  - OBJECTIVE: Iron has been suggested to play a role in the etiology of type 2
      diabetes mellitus (T2DM). Except for ferritin, evidence is sparse for other
      markers of iron metabolism that are regulated differently and might act through
      independent pathways. We therefore investigated the associations of serum
      ferritin, transferrin, soluble transferrin receptor (sTfR), transferrin
      saturation (TSAT), sTfR-to-log10ferritin (sTfR-F) index, and iron with impaired
      glucose metabolism (IGM/'prediabetes'), T2DM, and four continuous glucose and
      insulin traits. DESIGN AND METHODS: Data from 2893 participants of the population
      based Cooperative Health Research in the Region of Augsburg (KORA) F4 study
      (Germany) was investigated through regression analysis. The results were adjusted
      for socio-demographic, life-style, and obesity measures as well as metabolic,
      inflammatory, and other iron biomarkers following a step-wise approach. Non
      linearity was tested by adding a non-linear spline component to the model.
      RESULTS: Ferritin and transferrin were positively associated with IGM (fourth vs
      first sex-specific quartile: ferritin odds ratio (OR)=2.08 (95% CI 1.43-3.04) and
      transferrin OR=1.89 (95% CI 1.32-2.70)), T2DM (ferritin OR=1.98 (95% CI 1.22
      3.22) and transferrin OR=2.42 (95% CI 1.54-3.81)), and fasting as well as 2-h
      glucose. TSAT (OR=0.55 (95% CI 0.34-0.88)) and iron (OR=0.61 (95% CI 0.38-0.97))
      were inversely associated with T2DM, sTfR-F-index was inversely associated with
      IGM (OR=0.67 (95% CI 0.48-0.95)). There was no strong evidence for non-linear
      relationships. CONCLUSIONS: The observed associations of several markers of iron
      metabolism with hyperglycemia and insulin resistance suggest that iron stores as
      well as iron-related metabolic pathways contribute to the pathogenesis of IGM and
      T2DM. Moreover, TSAT levels are decreased in T2DM patients.

PMID- 26294795
TI  - Differential effects of viral silencing suppressors on siRNA and miRNA loading
      support the existence of two distinct cellular pools of ARGONAUTE1.

PMID- 26294794
TI  - Adrenal suppression in patients taking inhaled glucocorticoids is highly
      prevalent and management can be guided by morning cortisol.
AB  - CONTEXT: Up to 3% of US and UK populations are prescribed glucocorticoids (GC).
      Suppression of the hypothalamo-pituitary-adrenal axis with the potential risk of
      adrenal crisis is a recognized complication of therapy. The 250 MUg short
      Synacthen stimulation test (SST) is the most commonly used dynamic assessment to
      diagnose adrenal insufficiency. There are challenges to the use of the SST in
      routine clinical practice, including both the staff and time constraints and a
      significant recent increase in Synacthen cost. METHODS: We performed a
      retrospective analysis to determine the prevalence of adrenal suppression due to
      prescribed GCs and the utility of a morning serum cortisol for rapid assessment
      of adrenal reserve in the routine clinical setting. RESULTS: In total, 2773
      patients underwent 3603 SSTs in a large secondary/tertiary centre between 2008
      and 2013 and 17.9% (n=496) failed the SST. Of 404 patients taking oral, topical,
      intranasal or inhaled GC therapy for non-endocrine conditions, 33.2% (n=134) had
      a subnormal SST response. In patients taking inhaled GCs without additional GC
      therapy, 20.5% (34/166) failed an SST and suppression of adrenal function
      increased in a dose-dependent fashion. Using receiver operating characteristic
      curve analysis in patients currently taking inhaled GCs, a basal cortisol >=348
      nmol/l provided 100% specificity for passing the SST; a cortisol value <34 nmol/l
      had 100% sensitivity for SST failure. Using these cut-offs, 50% (n=83) of SSTs
      performed on patients prescribed inhaled GCs were unnecessary. CONCLUSION:
      Adrenal suppression due to GC treatment, particularly inhaled GCs, is common. A
      basal serum cortisol concentration has utility in helping determine which
      patients should undergo dynamic assessment of adrenal function.

PMID- 26294796
TI  - Mutant Cullin causes cardiovascular compromise.

PMID- 26294797
TI  - Reply to Tennant and Post.

PMID- 26294798
TI  - Production of False-Positive Immunoglobulin M Antibodies to Hepatitis A Virus in
      Autoimmune Events.

PMID- 26294799
TI  - From Big Data to Knowledge in the Social Sciences.
AB  - One of the challenges associated with high-volume, diverse datasets is whether
      synthesis of open data streams can translate into actionable knowledge.
      Recognizing that challenge and other issues related to these types of data, the
      National Institutes of Health developed the Big Data to Knowledge or BD2K
      initiative. The concept of translating "big data to knowledge" is important to
      the social and behavioral sciences in several respects. First, a general shift to
      data-intensive science will exert an influence on all scientific disciplines, but
      particularly on the behavioral and social sciences given the wealth of behavior
      and related constructs captured by big data sources. Second, science is itself a
      social enterprise; by applying principles from the social sciences to the conduct
      of research, it should be possible to ameliorate some of the systemic problems
      that plague the scientific enterprise in the age of big data. We explore the
      feasibility of recalibrating the basic mechanisms of the scientific enterprise so
      that they are more transparent and cumulative; more integrative and cohesive; and
      more rapid, relevant, and responsive.

PMID- 26294800
TI  - Macromolecular Design via an Organocatalytic, Monomer-Specific and Temperature
      Dependent "On/Off Switch". High Precision Synthesis of Polyester/Polycarbonate
      Multiblock Copolymers.
AB  - The employment of a monomer-specific "on/off switch" was used to synthesize a
      nine-block copolymer with a predetermined molecular weight and narrow
      distribution (D = 1.26) in only 2.5 h. The monomers consisted of a six-membered
      cyclic carbonate (i.e., 2-allyloxymethyl-2-ethyl-trimethylene carbonate (AOMEC))
      and epsilon-caprolactone (epsilonCL), which were catalyzed by 1,5,7
      triazabicyclo[4.4.0]-dec-5-ene (TBD). The dependence of polymerization rate with
      temperature was different for the two monomers. Under similar reaction
      conditions, the ratio of the apparent rate constant of AOMEC and epsilonCL
      [kpapp(AOMEC)/kpapp(epsilonCL)] changes from 400 at T = -40  degrees C to 50 at T
      = 30  degrees C and 10 at T = 100  degrees C. Therefore, by decreasing the
      copolymerization temperature from 30  degrees C to -40  degrees C, the conversion
      of epsilonCL can be switched "off", and by increasing the temperature to 30 
      degrees C, the conversion of epsilonCL can be switched "on" again. The addition
      of AOMEC at T = -40  degrees C results in the formation of a pure carbonate
      block. The cyclic addition of AOMEC to a solution of epsilonCL along with a
      simultaneous temperature change leads to the formation of multiblock copolymers.
      This result provides a new straightforward synthetic route to degradable
      multiblock copolymers, yielding new interesting materials with endless structural
      possibilities.

PMID- 26294801
TI  - Statistical Analysis of Q-matrix Based Diagnostic Classification Models.
AB  - Diagnostic classification models have recently gained prominence in educational
      assessment, psychiatric evaluation, and many other disciplines. Central to the
      model specification is the so-called Q-matrix that provides a qualitative
      specification of the item-attribute relationship. In this paper, we develop
      theories on the identifiability for the Q-matrix under the DINA and the DINO
      models. We further propose an estimation procedure for the Q-matrix through the
      regularized maximum likelihood. The applicability of this procedure is not
      limited to the DINA or the DINO model and it can be applied to essentially all Q
      matrix based diagnostic classification models. Simulation studies are conducted
      to illustrate its performance. Furthermore, two case studies are presented. The
      first case is a data set on fraction subtraction (educational application) and
      the second case is a subsample of the National Epidemiological Survey on Alcohol
      and Related Conditions concerning the social anxiety disorder (psychiatric
      application).

PMID- 26294802
TI  - Statistical analysis of bivariate failure time data with Marshall-Olkin Weibull
      models.
AB  - This paper discusses parametric analysis of bivariate failure time data, which
      often occur in medical studies among others. For this, as in the case of
      univariate failure time data, exponential and Weibull models are probably the
      most commonly used ones. However, it is surprising that there seem no general
      estimation procedures available for fitting the bivariate Weibull model to
      bivariate right-censored failure time data except some methods for special
      situations. We present and investigate two general but simple estimation
      procedures, one being a graphical approach and the other being a marginal
      approach, for the problem. An extensive simulation study is conducted to assess
      the performances of the proposed approaches and shows that they work well for
      practical situations. An illustrative example is provided.

PMID- 26294803
TI  - Alcohol and Other Drug Use in Middle School: The Interplay of Gender, Peer
      Victimization, and Supportive Social Relationships.
AB  - The current study examined the impact of supportive social relationships (i.e.,
      teacher support, adult support, school relatedness) and peer victimization on
      middle school students' substance use. Over 3,000 middle school students reported
      on alcohol, cigarette, and marijuana use, supportive social relationships, and
      instances in which they were the victim of aggressive behavior. Mixed-effects
      logit regression analyses revealed complementary patterns of results across types
      of substances. Students who perceived high levels of social support were less
      likely to report alcohol and drug use initiation, particularly at low levels of
      peer victimization. Gender moderated the negative effect of peer victimization,
      with highly victimized boys most likely to report alcohol, cigarette, and
      marijuana use. Results indicated a complex interplay of social influences and
      moderating variables in predicting early onset alcohol and other drug use, one
      that researchers should consider when studying adolescents' decisions to use
      alcohol and other drugs.

PMID- 26294804
TI  - Oligosilanylsilatranes.
AB  - Oligosilanes with attached silatranyl units were obtained by reactions of
      potassium oligosilanides with a silatranyl triflate. Interaction between Si and N
      atoms was observed in the 29Si NMR spectra (upfield-shifted SiO3 resonances) and
      in the solid-state structures (Si-N distances between 2.29 and 2.16 A). The Si-N
      interaction can be "switched off" either by protonation of the nitrogen lone pair
      or by potassium silanide formation caused by trimethylsilyl group cleavage in the
      presence of potassium tert-butoxide.

PMID- 26294805
TI  - Wagner-Meerwein-Type Rearrangements of Germapolysilanes - A Stable Ion Study.
AB  - The rearrangement of tris(trimethylsilyl)silyltrimethylgermane 1 to give
      tetrakis(trimethylsilyl)germane 2 was investigated as a typical example for Lewis
      acid catalyzed Wagner-Meerwein-type rearrangements of polysilanes and
      polygermasilanes. Direct 29Si NMR spectroscopic evidence is provided for several
      cationic intermediates during the reaction. The identity of these species was
      verified by independent synthesis and NMR characterization, and their
      transformation was followed by NMR spectroscopy.

PMID- 26294806
TI  - Halide-Mediated Ortho-Deprotonation Reactions Applied to the Synthesis of 1,2-
      and 1,3-Disubstituted Ferrocene Derivatives.
AB  - The ortho-deprotonation of halide-substituted ferrocenes by treatment with
      lithium tetramethylpiperidide (LiTMP) has been investigated. Iodo-, bromo-, and
      chloro-substituted ferrocenes were easily deprotonated adjacent to the halide
      substituents. The synthetic applicability of this reaction was, however, limited
      by the fact that, depending on the temperature and the degree of halide
      substitution, scrambling of both iodo and bromo substituents at the ferrocene
      core took place. Iodoferrocenes could not be transformed selectively into ortho
      substituted iodoferrocenes since, in the presence of LiTMP, the iodo substituents
      scrambled efficiently even at -78  degrees C, and this process had occurred
      before electrophiles had been added. Bromoferrocene and certain monobromo
      substituted derivatives, however, could be efficiently ortho-deprotonated at low
      temperature and reacted with a number of electrophiles to afford 1,2- and 1,2,3
      substituted ferrocene derivatives. For example, 2-bromo-1-iodoferrocene was
      synthesized by ortho-deprotonation of bromoferrocene and reaction with the
      electrophiles diiodoethane and diiodotetrafluoroethane, respectively. In this and
      related cases the iodide scrambling process and further product deprotonation due
      to the excess LiTMP could be suppressed efficiently by running the reaction at
      low temperature and in inverse mode. In contrast to the low-temperature process,
      at room temperature bromo substituents in bromoferrocenes scrambled in the
      presence of LiTMP. Chloro- and 1,2-dichloroferrocene could be ortho-deprotonated
      selectively, but in neither case was scrambling of a chloro substituent observed.
      As a further application of this ortho-deprotonation reaction, a route for the
      synthesis of 1,3-disubstituted ferrocenes was developed. 1,3-Diiodoferrocene was
      accessible from bromoferrocene in four steps. On a multigram scale an overall
      yield of 41% was achieved. 1,3-Diiodoferrocene was further transformed into
      symmetrically 1,3-disubstituted ferrocenes (1,3-R2Fc; R = CHO, COOEt, CN,
      CH=CH2).

PMID- 26294809
TI  - Corrigendum to "The Analysis of Sialylation, N-Glycan Branching, and Expression
      of O-Glycans in Seminal Plasma of Infertile Men".

PMID- 26294807
TI  - The Clinical and Pathological Significance of Nectin-2 and DDX3 Expression in
      Pancreatic Ductal Adenocarcinomas.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant disease, but the
      genetic basis of PDAC is still unclear. In this study, Nectin-2 and DDX3
      expression in 106 PDAC, 35 peritumoral tissues, 55 benign pancreatic lesions, and
      13 normal pancreatic tissues were measured by immunohistochemical methods.
      Results showed that the percentage of positive Nectin-2 and DDX3 expression was
      significantly higher in PDAC tumors than in peritumoral tissues, benign
      pancreatic tissues, and normal pancreatic tissues (P < 0.01). The percentage of
      cases with positive Nectin-2 and DDX3 expression was significantly lower in PDAC
      patients without lymph node metastasis and invasion and having TNM stage I/II
      disease than in patients with lymph node metastasis, invasion, and TNM stage
      III/IV disease (P < 0.05 or P < 0.01). Positive DDX3 expression is associated
      with poor differentiation of PDAC. Kaplan-Meier survival analysis showed that
      positive Nectin-2 and DDX3 expression were significantly associated with survival
      in PDAC patients (P < 0.001). Cox multivariate analysis revealed that positive
      Nectin-2 and DDX3 expression were independent poor prognosis factors in PDAC
      patients. In conclusion, positive Nectin-2 and DDX3 expression are associated
      with the progression and poor prognosis in PDAC patients. 

PMID- 26294808
TI  - Carboxyhemoglobin Formation in Preterm Infants Is Related to the Subsequent
      Development of Bronchopulmonary Dysplasia.
AB  - OBJECTIVE: To evaluate the usefulness of carboxyhemoglobin (CO-Hb) levels as a
      biomarker to predict the development and severity of bronchopulmonary dysplasia
      (BPD). METHODS: Twenty-five infants born at <33 wk of gestational age or with a
      birth weight of <1,500 g were enrolled. CO-Hb levels were measured between
      postnatal days 5 and 8, 12 and 15, 19 and 22, and 26 and 29. Urinary levels of 8
      hydroxydeoxyguanosine (8-OHdG), advanced oxidation protein products, and Nepsilon
      (hexanoyl) lysine were measured between postnatal days 5 and 8 and 26 and 29.
      Receiver operating characteristic (ROC) analysis was used to compare the
      biomarkers' predictive values. RESULTS: Compared with infants in the no-or-mild
      BPD group, infants with moderate-to-severe BPD exhibited higher CO-Hb levels
      during the early postnatal period and higher 8-OHdG levels between postnatal days
      5 and 8. Using ROC analysis to predict the development of moderate-to-severe BPD,
      the area under the curve (AUC) for CO-Hb levels between postnatal days 5 and 8
      was higher than AUCs for the urinary markers. CONCLUSIONS: CO-Hb levels during
      the early postnatal period may serve as a practical marker for evaluating
      oxidative stress and the severity of subsequently developing BPD.

PMID- 26294810
TI  - Improving Low-Income Preschoolers' Theory of Mind: A Training Study.
AB  - This study examined the efficacy of training theory of mind via storybook
      interactions focused on characters' mental states (i.e., beliefs and emotions) in
      a sample of 73 low-income preschoolers, and determined if training transferred to
      social competence. Children in the experimental group participated in
      experimenter-led book interactions in which characters' false beliefs and
      emotions were discussed. Children in the first control group were read the same
      stories, but without the embedded discussions; children in the second control
      group were not read books. Children's false belief understanding, emotion
      understanding, and social competence were assessed at pretest, an immediate
      posttest, and a delayed posttest two months later. Children in the experimental
      group outperformed both controls on false belief understanding, but not emotion
      understanding or social competence, at both posttests.

PMID- 26294813
TI  - The ch in children stands for cherish.

PMID- 26294811
TI  - Gene-environment interaction on neural mechanisms of orthographic processing in
      Chinese children.
AB  - The ability to process and identify visual words requires efficient orthographic
      processing of print, consisting of letters in alphabetic languages or characters
      in Chinese. The N170 is a robust neural marker for orthographic processes. Both
      genetic and environmental factors, such as home literacy, have been shown to
      influence orthographic processing at the behavioral level, but their relative
      contributions and interactions are not well understood. The present study aimed
      to reveal possible gene-by-environment interactions on orthographic processing at
      the behavioral and neural level in a normal children sample. Sixty 12 year old
      Chinese children from a 10-year longitudinal sample underwent an implicit visual
      word color decision task on real words and stroke combinations. The ERP analysis
      focused on the increase of the occipito-temporal N170 to words compared to stroke
      combinations. The genetic analysis focused on two SNPs (rs1419228, rs1091047) in
      the gene DCDC2 based on previous findings linking these 2 SNPs to orthographic
      coding. Home literacy was measured previously as the number of children's books
      at home, when the children were at the age of 3. Relative to stroke combinations,
      real words evoked greater N170 in bilateral posterior brain regions. A
      significant interaction between rs1091047 and home literacy was observed on the
      changes of N170 comparing real words to stroke combinations in the left
      hemisphere. Particularly, children carrying the major allele "G" showed a similar
      N170 effect irrespective of their environment, while children carrying the minor
      allele "C" showed a smaller N170 effect in low home-literacy environment than
      those in good environment.

PMID- 26294815
TI  - Eastern Cape treatment dysfunction boosts virulent new XDR-TB strain.

PMID- 26294816
TI  - The risky lives of South Africa's children: Why so many die or are traumatised.

PMID- 26294817
TI  - Carbohydrate loading in the preoperative setting.
AB  - Nutrition support is an evolving field, and modern clinical nutrition practice
      should actively incorporate strategies to enhance various clinical outcomes. In
      surgical patients, clinical benefits can be maximised by nutritional support
      protocols that minimise and manage the perioperative fasting period. This
      approach, which includes the perioperative provision of clear carbohydrate
      containing fluids, has been shown to be safe, is evidence based, and is supported
      by many professional societies. Such a strategy has been shown to aid the
      anaesthetic process and maintain an optimal metabolic state, including improved
      insulin sensitivity and blunted muscle catabolic activity. Some important
      consequences of this improved metabolic control include shorter hospital stay and
      fewer postoperative complications. A proactive multidisciplinary team approach is
      essential to use this nutrition support strategy with success across a hospital's
      surgical service.

PMID- 26294818
TI  - Recommendations for the treatment and prevention of malaria: Update for the 2015
      season in South Africa.
AB  - Notified malaria cases in South Africa (SA) decreased significantly over the past
      14 years, from over 60 000 in the 1999/2000 malaria season to less than 13 000 in
      2013/2014. However, the past two seasons have seen increases in both local and
      imported cases. Mozambique contributes the highest number of imported cases in
      SA. This update provides recommendations for malaria treatment and prevention (in
      travellers and residents) for 2015.

PMID- 26294819
TI  - Chronic pancreatitis, depression and substance use disorders: A not uncommon
      combination.
AB  - Chronic pancreatitis (CP) is a progressive and debilitating disease. A
      potentially important consideration is the relationship between CP, depression
      and substance use disorders, which seems to be circular and multiplicative. Pain
      management is a critical component of intervention, and it would seem that in the
      context of chronic illness this requires a biopsychosocial approach aiming for a
      tailored intervention that strikes an appropriate therapeutic balance.

PMID- 26294820
TI  - 'Over-servicing 'underservicing' and 'abandonment': What is the law?
AB  - The Ethical Rules and Policy Document of the Health Professions Council of South
      Africa (HPCSA) do not define 'over-servicing', 'underservicing' and 'abandonment.
      The HPCSA Guidelines on Over-servicing, Perverse Incentives and Related Matters
      define 'over-service' only. The converse of this definition can be used to define
      'underservicing'. The courts do not refer to these concepts, but apply general
      rules regarding professional negligence and malpractice based on what a
      reasonably competent doctor in the same position would do. In deciding the
      standard to be adopted, the courts may consult the ethical rules of the medical
      profession, but are not bound to take them into account.

PMID- 26294821
TI  - The Global Status Report on Violence Prevention 2014: Where to for the South
      African health sector?

PMID- 26294822
TI  - Prevention of Liver Fibrosis and Cancer in Africa: The PROLIFICA project--a
      collaborative study of hepatitis B-related liver disease in West Africa.

PMID- 26294823
TI  - Need for services for the care and prevention of congenital disorders in South
      Africa as the country's epidemiological transition evolves.

PMID- 26294824
TI  - Dementia in rural South Africa: A pressing need for epidemiological studies.

PMID- 26294825
TI  - The Vaccine and Cervical Cancer Screen project 2 (VACCS 2): Linking cervical
      cancer screening to a two-dose HPV vaccination schedule in the South-West
      District of Tshwane, Gauteng, South Africa.
AB  - BACKGROUND: Cervical cancer is a preventable disease with a high prevalence in
      South Africa (SA), where screening is opportunistic. Primary prevention is now
      possible through HPV vaccination. In VACCS 1 the feasibility of linking cervical
      cancer with HPV vaccination was demonstrated. OBJECTIVES: To investigate the
      feasibility of linking HPV self-testing with a two-dose HPV vaccination schedule
      and to compare results with VACCS 1. METHODS: The project was conducted in five
      schools in the South-West District of Tshwane, Gauteng, SA. Leaflet information
      on cervical cancer and screening was provided, with requests for consent and
      assent for a two-dose HPV vaccination of schoolgirls. Female caregivers were
      invited to take part in HPV self-screening. RESULTS: Of 965 girls invited for
      vaccination, 519 (53.7%) had full consent and 518 (99.8%) received at least one
      vaccine dose. The invited uptake rate was 53.7% and 495 girls received both
      doses, giving a completion rate of 95.4% v. 82.6% in VACCS 1. Of 1 135 self
      screen kits handed out, 560 (49.3%) were not returned. The mean age (standard
      deviation) of the 160 women who participated in self-screening was 38.7 (7.7)
      years. HPV testing was negative in 116 women (72.5%), 15 women (9.4%) tested
      positive for HPV 16 and/or 18, and 27 (16.9%) were positive for non-16/18
      oncogenic HPV. CONCLUSION: Data from the VACCS projects suggest that school-based
      vaccine programmes can be successfully implemented. A two-dose schedule allowed
      for higher completion rates. Linking self-collected HPV screening to HPV
      vaccination is feasible, is a promising and viable screening strategy, and
      reached the appropriate age group for screening.

PMID- 26294826
TI  - Traumatic brain injury, the hidden pandemic: A focused response to family and
      patient experiences and needs.
AB  - INTRODUCTION: Traumatic brain injury (TBI) has many potential cognitive,
      behavioural and psychological consequences, and contributes significantly to the
      national burden of disease and to ongoing violent behaviour. Few resources are
      available for the rehabilitation of patients with TBI in South Africa, and access
      to rehabilitation facilities in the public sector is limited. Consequently, it is
      the families impacted on by TBI that ultimately carry the care and rehabilitation
      burden once survivors are discharged from hospital. Families are generally ill
      equipped to cope with the complex and potentially long-term disabilities that
      accompany brain injury. METHODS: Reviewing interviews with 175 family members and
      354 patients recovering from TBI helped identify the key challenges that the
      survivors of TBI and their families face. RESULTS: Nine problem areas were
      identified that formed the basis for development of a discharge resource, the S
      Plan, which serves to inform patients and carers and provide practical solutions
      for the problems they face. CONCLUSION: The experiences of TBI survivors and
      their family members served to inform the development of simple, integrated
      coping strategies, namely two S-Plan tools, one for survivors and their
      families/caregivers and the other for care workers, in conjunction with
      counselling and support group processes. The S-Plan constitutes a discharge
      resource to inform patients and carers and provide practical solutions for the
      problems they face in caring for family members who have suffered TBI.

PMID- 26294827
TI  - Hypertension, end-stage renal disease and mesangiocapillary glomerulonephritis in
      methamphetamine users.
AB  - BACKGROUND: Methamphetamine abuse has risen dramatically in South Africa. The
      chronic effects of abuse on the kidneys and blood pressure have not been
      documented. This study reviewed patients referred for evaluation of kidney
      disease and/or hypertension, who had been abusing methamphetamines. METHODS: The
      records of patients referred to the renal unit between 2005 and 2013 who had been
      using methamphetamines were retrospectively reviewed. Patient demographics,
      biophysical parameters, blood pressure, renal function, renal ultrasound and
      biopsy findings, complications of chronic kidney disease and comorbidities were
      recorded. RESULTS: Forty-seven patients were included in the study. Their mean
      age was 29 years. Hypertension was present in 42 (89.4%) of patients, with
      malignant hypertension in 21 (44.7%). Forty-five (95.7%) had chronic kidney
      disease (CKD), and 26 (55.3%) had end-stage renal disease. Renal biopsies were
      performed in 24 patients. Twelve (50.0%) of the biopsies showed hypertensive
      changes and 14 (58.3%) mesangiocapillary glomerulonephritis type 1, with
      deposition of IgM and C3 complement. CONCLUSION: Methamphetamine use is
      associated with severe hypertension, mesangiocapillary glomerulonephritis and
      CKD.

PMID- 26294828
TI  - Emergency care research priorities in South Africa.
AB  - BACKGROUND: Emergency care research is rarely undertaken in low- and middle
      income countries. A manageable 'road map' for research in South African (SA)
      emergency care is needed to address research gaps. OBJECTIVE: To identify,
      collate and prioritise research topics from identified knowledge gaps in
      emergency care in SA. METHODS: Seventy-six individuals were invited to
      participate in a modified Delphi study. Participants were requested to suggest
      important research topics before rating them. Consensus was achieved when >75% of
      participants strongly agreed or disagreed. Participants then ranked the agreed
      statements before selecting the most appropriate methodology relating to study
      design, funding and collaboration. RESULTS: Three hundred and fifty topics were
      suggested by 31 participants. Topics were collated into 123 statements before
      participants rated them. Consensus was achieved for 39 statements. The highest
      ranked priority in the prehospital group was to determine which prehospital
      interventions improve outcomes in critically ill patients. The competence of
      emergency care providers in performing common lifesaving skills was deemed the
      most important in clinical emergency care. Implementing and reviewing quality
      improvement systems scored the highest under general systems and safety
      management. Only 22 statements achieved consensus regarding study design. The
      National Department of Health was the preferred funding source, while private
      organisations and emergency care societies were identified as possible
      collaborative partners. CONCLUSION: This study provides expert consensus on
      priority research areas in emergency care in SA as a guide for emergency care
      providers to ensure evidence-based care that is relevant to the SA population.

PMID- 26294829
TI  - Oral v. pulse intravenous cyclophosphamide: A retrospective analysis of adverse
      events in a setting with a high burden of infectious disease.
AB  - BACKGROUND: Cyclophosphamide (CPM) is still considered to be the first-line
      treatment for many life-threatening autoimmune conditions. It does, however,
      carry a significant risk of serious adverse events, especially infections. At
      present CPM is administered as either a daily oral dose (DOC) or an intravenous
      pulse (PIVC). There is uncertainty regarding the safety profiles of both regimens
      in settings with a high burden of infectious diseases. OBJECTIVE: To compare the
      frequency and nature of adverse events related to the use of DOC and PIVC in such
      a setting. METHODS: A cohort of patients treated with CPM for autoimmune diseases
      at Tygerberg Academic Hospital, Cape Town, South Africa, from 1 January 2008 to
      31 May 2013 was studied. We compared participants receiving DOC and PIVC with
      regard to disease characteristics and the occurrence of major adverse events.
      RESULTS: A total of 134 participants (92 DOC and 42 PIVC) were included.
      Participants in the DOC group were treated for longer (174 v. 101 days; p<0.01)
      and with higher cumulative doses (17 276 v. 3 327 mg; p<0.01). Risk of infection
      was similar in the two groups, although there were 6 deaths from leucopenic
      sepsis in the DOC group (v. 0; p=0.18). Nadir leucocyte counts were also lower in
      the DOC group (median 3.8 v. 5.3 * 109/L; p=0.02). CONCLUSION: Infection rates in
      the two groups were similar, but DOC was associated with longer treatment
      duration, greater cumulative CPM doses and more severe leucopenia. If resources
      allow and available literature provides support for efficacy, consideration
      should be given to greater use of PIVC.

PMID- 26294830
TI  - Prevalence and causes of thrombocytopenia in an academic state-sector laboratory
      in Soweto, Johannesburg, South Africa.
AB  - BACKGROUND: Causes of thrombocytopenia range from laboratory errors to life
      threatening pathological conditions. To establish the cause, appropriate
      laboratory investigation is required. OBJECTIVES: To determine the prevalence and
      causes of platelet counts <100 * 10(9)/L in state health facilities in
      Johannesburg, South Africa, as well as the quality of the subsequent laboratory
      work-up in this setting. METHODS: Full blood counts (FBCs) performed on 7
      randomly selected days at the National Health Laboratory Service laboratory at
      Chris Hani Baragwanath Academic Hospital were retrospectively reviewed. Samples
      with platelet counts <100 * 109/L were identified, and pertinent information was
      extracted from the laboratory database. RESULTS: Of 4 456 FBCs included, 381
      (8.6%) had a platelet count of <100 * 10(9)/L. Thrombocytopenia prevalence rates
      were high in haematology/oncology wards (34.4%), intensive care units (20.5%) and
      medical wards (18.7%) and among neonatal inpatients (16.5%), and were lowest in
      outpatient clinics (1-2%). A cause was apparent in ~60% of patients, the
      commonest causes being chemotherapy and sepsis (each comprising >20% of the
      recognised causes). Spurious thrombocytopenia, disseminated tuberculosis,
      aplastic anaemia, immune thrombocytopenia and malignant marrow infiltration each
      accounted for 5 - 10% of the causes, while malaria, thrombotic thrombocytopenic
      purpura, HIV effect and liver disease were each identified in <5% of cases. HIV
      status was documented in ~70% of the patients, of whom ~50% tested positive. The
      quality of the laboratory work-up showed differences between specialties within
      the hospital setting, and was poorest in the primary healthcare clinic sector.
      CONCLUSION: Thrombocytopenia is common in hospitalised patients in the
      Johannesburg academic state sector. Differences in the quality of the laboratory
      work-up emphasise the need for a standardised approach to thrombocytopenia
      investigation and increased awareness among clinicians.

PMID- 26294831
TI  - Short-term treatment outcomes of children starting antiretroviral therapy in the
      intensive care unit, general medical wards and outpatient HIV clinics at Red
      Cross War Memorial Children's Hospital, Cape Town, South Africa: A retrospective
      cohort study.
AB  - BACKGROUND: Many HIV-infected children are initiated on antiretroviral therapy
      (ART) during hospitalisation in South Africa (SA). No published data on these
      outcomes exist. OBJECTIVES: To assess the short-term outcomes of children
      initiated on ART in the intensive care unit (ICU), general medical wards (GMWs)
      and outpatient HIV clinics (OHCs) at Red Cross War Memorial Children's Hospital
      (RCWMCH), Cape Town, SA. METHODS: We conducted a retrospective cohort study of
      HIV-infected children aged <13 years commenced on first-line ART between January
      2008 and December 2011. Outcomes included death, virological suppression and
      changes in CD4 count. Kaplan-Meier estimates, multivariate Cox proportional
      hazard ratios and logistic regression were used to estimate outcomes at 6 months.
      RESULTS: One hundred and six children were commenced on ART in the ICU, 509 in
      the GMWs and 127 in the OHCs; 65.7% of all children were <12 months old. Of
      children qualifying for rapid ART initiation according to the 2013 national
      treatment guidelines, 182 (24.9%) started therapy within 7 days of diagnosis.
      Overall mortality was 6.4% (95% confidence interval (CI) 4.9 - 8.4). Of children
      remaining in care at RCWMCH, 51.0% achieved a CD4 percentage >=25% and 62.3% a
      viral load <=50 copies/mL 6 months after ART initiation. Mortality was higher in
      the ICU cohort (13.2%) than in the GMW and OHC cohorts (5.5% and 3.9%,
      respectively, log-rank p=0.004). Predictors of mortality included moderate
      underweight (adjusted hazard ratio (aHR) 2.4; 95% CI 1.1 - 5.2), severe
      underweight (aHR 3.2; 95% CI 1.6 - 6.5), absence of caregiver counselling
      sessions (aHR 2.9; 95% CI 1.4 - 6.0) and ART initiation in the ICU (aHR 2.6; 95%
      CI 1.4 - 4.9). CONCLUSION: These results highlight the importance of
      understanding the context in which children initiate ART, when comparing outcomes
      in different settings.

PMID- 26294832
TI  - An investigation of fingerstick blood collection for point-of-care HIV-1 viral
      load monitoring in South Africa.
AB  - BACKGROUND: Viral load (VL) quantification is an important tool in determining
      newly developed drug resistance or problems with adherence to antiretroviral
      therapy (ART) in HIV-positive patients. VL monitoring is becoming the standard of
      care in many resource-limited settings. Testing in resource-limited settings may
      require sampling by fingerstick because of general shortages of skilled
      phlebotomists and the expense of venepuncture supplies and problems with their
      distribution. OBJECTIVE: To assess the feasibility and ease of collecting 150 uL
      capillary blood needed for the use of a novel collection device following a
      classic fingerstick puncture. METHODS: Patients were recruited by the study nurse
      upon arrival for routine ART monitoring at the Themba Lethu Clinic in
      Johannesburg, South Africa. Each step of the fingerstick and blood collection
      protocol was observed, and their completion or omission was recorded. RESULTS:
      One hundred and three patients consented to the study, of whom three were
      excluded owing to the presence of callouses. From a total of 100 patients who
      consented and were enrolled, 98% of collection attempts were successful and 86%
      of participants required only one fingerstick to successfully collect 150 uL
      capillary blood. Study nurse adherence to the fingerstick protocol revealed
      omissions in several steps that may lower the success rate of capillary blood
      collection and reduce the performance of a subsequent VL assay. CONCLUSION: The
      findings of this study support the feasibility of collecting 150 uL of capillary
      blood via fingerstick for point-of-care HIV-1 VL testing in a resource-limited
      setting.

PMID- 26294833
TI  - Significance, definition, classification and risk factors of chronic kidney
      disease in South Africa.
AB  - Renal dysfunction or chronic kidney disease (CKD) is found in 10% of the global
      population and is classified into five stages according to the estimated
      glomerular filtration rate (eGFR). No matter where a patient lives, estimation of
      the GFR is mandatory for decision-making and obtained by the simple measurement
      of a serum creatinine level. The objective of diagnosing CKD lies in its future
      prevention, early detection and proper treatment, which will prevent or delay
      functional deterioration. Primary hypertension (PH) occurs in 25% of South Africa
      (SA)s black population and is the putative cause of stage 5 CKD in 40 - 60% of
      these patients. Moreover, in this group, stage 5 CKD occurs at a relatively young
      age (35 - 45 years) compared with other population groups in whom stage 5 CKD
      resulting from PH usually occurs between 60 and 70 years of age. In the cohort
      study, PH has been found in 12 - 16% of black school learners (mean age 17 years)
      compared with 1.8 - 2% of other ethnic groups (mixed race, Asian, white). End
      stage renal failure (ESRF) is the fifth most common cause of death in SA,
      excluding post-traumatic cases. In addition, undiagnosed or poorly controlled PH
      is a potent risk factor for other cardiovascular disease (CVD), e.g. congestive
      cardiac failure, myocardial infarction, stroke. Significant protein is also
      associated with CVD and protein >1 g/d is a significant risk factor for ESRF.

PMID- 26294835
TI  - Conflict of interest and regulatory authorities.

PMID- 26294836
TI  - Inaugural International Association of Student Surgical Societies Symposium.

PMID- 26294837
TI  - Will Basson come out on top?

PMID- 26294838
TI  - Zuma's legal advisors 'led him astray', turned healthcare professionals into
      criminals.

PMID- 26294839
TI  - Ajay Makanjee.

PMID- 26294840
TI  - Carbohydrate loading in the preoperative setting.
AB  - Nutrition support is an evolving field, and modern clinical nutrition practice
      should actively incorporate strategies to enhance various clinical outcomes. In
      surgical patients, clinical benefits can be maximised by nutritional support
      protocols that minimise and manage the perioperative fasting period. This
      approach, which includes the perioperative provision of clear carbohydrate
      containing fluids, has been shown to be safe, is evidence based, and is supported
      by many professional societies. Such a strategy has been shown to aid the
      anaesthetic process and maintain an optimal metabolic state, including improved
      insulin sensitivity and blunted muscle catabolic activity. Some important
      consequences of this improved metabolic control include shorter hospital stay and
      fewer postoperative complications. A proactive multidisciplinary team approach is
      essential to use this nutrition support strategy with success across a hospital's
      surgical service.

PMID- 26294842
TI  - Diagnostic approach to chronic kidney disease.

PMID- 26294841
TI  - Chronic kidney disease.
AB  - It is known that, for many reasons, general practitioners(GPs) find renal disease
      difficult to diagnose, understandand treat. The terms chronic kidney disease
      (CKD) andglomerular filtration rate (GFR), representing the renalfunction
      equation, have been introduced to clarify someof these difficulties.
      Unfortunately, even these pivotal concepts remaineither unknown or poorly
      understood by the majority of GPs in SouthAfrica (SA). CKD is often not
      recognised because there are no specificsymptoms, and not diagnosed or only
      diagnosed at an advanced stage.Tests for CKD are, however, simple and freely
      available.

PMID- 26294844
TI  - Clinical aspects of chronic kidney disease.

PMID- 26294845
TI  - List of contributors to the articles and information compiled by the National
      Kidney Foundation of South Africa.

PMID- 26294843
TI  - Management of patients with chronic kidney disease.

PMID- 26294846
TI  - CPD Questionnaire.

PMID- 26294847
TI  - The Effects of Early Institutionalization and Foster Care Intervention on
      Children's Social Behaviors at Age 8.
AB  - The present study compared the social behaviors of 8-year-old previously
      institutionalized Romanian children from the Bucharest Early Intervention Project
      (BEIP) in two groups: 1) children randomized to foster care homes (FCG), and 2)
      children randomized to care as usual (remaining in institutions) (CAUG). Children
      were observed interacting with an age and gender-matched unfamiliar, non
      institutionalized peer from the community (NIG) during six interactive tasks, and
      their behavior was coded for speech reticence, social engagement, task
      orientation, social withdrawal, and conversational competence. Group comparisons
      revealed that FCG children were rated as significantly less reticent during a
      speech task than CAUG children. For CAUG children, longer time spent in
      institutional care was related to greater speech reticence and lower social
      engagement. Using an Actor-Partner Interdependence Model, CAUG children's
      behaviors, but not FCG, were found to influence the behavior of unfamiliar peers.
      These findings are the first to characterize institutionalized children's
      observed social behaviors towards new peers during middle childhood and highlight
      the positive effects of foster care intervention in the social domain.

PMID- 26294848
TI  - Macrophage Differentiation from Monocytes Is Influenced by the Lipid Oxidation
      Degree of Low Density Lipoprotein.
AB  - LDL plays an important role in atherosclerotic plaque formation and macrophage
      differentiation. However, there is no report regarding the oxidation degree of
      LDL and macrophage differentiation. Our study has shown that the differentiation
      into M1 or M2 macrophages is related to the lipid oxidation level of LDL. Based
      on the level of lipid peroxidation, LDL is classified into high-oxidized LDL (hi
      oxLDL) and low-oxidized LDL (low-oxLDL). The differentiation profiles of
      macrophages were determined by surface receptor expression and cytokine secretion
      profiles. Low-oxLDL induced CD86 expression and production of TNF-alpha and IL
      12p40 in THP-1 cells, indicating an M1 macrophage phenotype. Hi-oxLDL induced
      mannose receptor expression and production of IL-6 and monocyte chemoattractant
      protein-1, which mostly match the phenotype of M2 macrophages. Further supporting
      evidence for an M2 polarization by hi-oxLDL was the induction of LOX-1 in THP-1
      cells treated with hi-oxLDL but not with low-oxLDL. Similar results were obtained
      in primary human monocytes. Therefore, our results strongly suggest that the
      oxidation degree of LDL influences the differentiation of monocytes into M1 or M2
      macrophages and determines the inflammatory fate in early stages of
      atherosclerosis. 

PMID- 26294849
TI  - Effect of Negative Pressure Therapy on the Inflammatory Response of the
      Intestinal Microenvironment in a Porcine Septic Model.
AB  - In a swine model of ischemia/reperfusion injury coupled with sepsis, we have
      previously shown attenuation of secondary organ injury and decreased mortality
      with negative pressure therapy (NPT). We hypothesized that NPT modulates the
      intestinal microenvironment by mediating the innate immune system. Sepsis was
      induced in 12 anesthetized female pigs. Group 1 (n = 6) was decompressed at 12
      hrs after injury (T 12) and treated with standard of care (SOC), and group 2 (n =
      6) with NPT for up to T 48. Immunoparalysis was evident as lymphocytopenia at T
      24 in both groups; however, survival was improved in the NPT group versus SOC
      (Odds ratio = 4.0). The SOC group showed significant reduction in lymphocyte
      numbers compared to NPT group by T 48 (p < 0.05). The capacity of peritoneal
      fluid to stimulate a robust reactive oxygen species response in vitro was greater
      for the NPT group, peaking at T 24 for both M1 (p = 0.0197) and M2 macrophages (p
      = 0.085). Plasma elicited little if any effect which was confirmed by microarray
      analysis. In this septic swine model NPT appeared to modulate the intestinal
      microenvironment, facilitating an early robust, yet transient, host defense
      mediated by M1 and M2 macrophages. NPT may help overcome immunoparalysis that
      occurs during inflammatory response to septic injury.

PMID- 26294851
TI  - Early sexual debut: Voluntary or coerced? Evidence from longitudinal data in
      South Africa--the Birth to Twenty Plus study.
AB  - BACKGROUND: Early sexual debut, voluntary or coerced, increases risks to sexual
      and reproductive health. Sexual coercion is increasingly receiving attention as
      an important public health issue owing to its association with adverse health and
      social outcomes. OBJECTIVE: To describe voluntary and coerced experience at
      sexual debut. METHODS: A longitudinal perspective among 2,216 adolescents (1,149
      females, 1,067 males) in a birth cohort study in South Africa, analysing data
      collected on six occasions between 11 and 18 years. RESULTS: The median age of
      sexual debut was 16 years for females and 15 for males. Reported coerced sexual
      debut included children < 11 years of age. Males reported earlier sexual debut
      with both voluntary and coerced sexual experience, than females (p < 0.0001).
      Sexual coercion at early sexual debut among both male and female adolescents
      occurred mostly through sexual intercourse with older adolescents and partners of
      the same age. CONCLUSION: The identified time periods and age groups need to be
      targeted for interventions to delay sexual debut and prevent sexual coercion
      among young people. More research is needed to understand underlying predisposing
      risk factors for sexual coercion at sexual debut, both early and not early.

PMID- 26294850
TI  - Relapse Contexts for Substance Abusing Adolescents with Comorbid Psychopathology.
AB  - The relationship of diagnosis, developmentally relevant factors (e.g., life
      stress, peer substance use) and mental health symptoms to contexts of a return to
      substance use were examined for 103 substance abusing adolescents with Axis I
      psychopathology (ages 12-17) following inpatient treatment. Proximal psychiatric
      symptoms and developmentally relevant factors, but not psychiatric diagnosis at
      treatment entry, predicted contexts in which youth returned to alcohol and drug
      use in the 6 months following treatment. The findings suggest that comorbid youth
      are similar to same-aged peers without comorbid psychopathology and adults with
      comorbid psychopathology in regard to contexts associated with a return to
      substance involvement.

PMID- 26294854
TI  - Another law change prevents proper healthcare delivery.

PMID- 26294856
TI  - Turning nutrition on its head--Noakes gets his day.

PMID- 26294855
TI  - The 'axe man' departs, offering hard-won lessons.

PMID- 26294857
TI  - Saving our newborns by doing the basics right--and keeping it simple.

PMID- 26294859
TI  - World's first successful penis transplant at Tygerberg Hospital.

PMID- 26294858
TI  - Basson slapped down by committee.

PMID- 26294860
TI  - Stephen Hough, 1947-2014.

PMID- 26294861
TI  - Basic and comprehensive emergency obstetric and neonatal care in 12 South African
      health districts.
AB  - AIM: To assess the functionality of healthcare facilities with respect to
      providing the signal functions of basic and comprehensive emergency obstetric
      care in 12 districts. SETTING: Twelve districts were selected from the 52
      districts in South Africa, based on the number of maternal deaths, the
      institutional maternal mortality ratio and the stillbirth rate for the district.
      METHODS: All community health centres (CHCs) and district, regional and tertiary
      hospitals were visited and detailed information was obtained on the ability of
      the facility to perform the basic (BEmONC) and comprehensive (CEmONC) emergency
      obstetric and neonatal care signal functions. RESULTS: Fifty-three CHCs, 63
      district hospitals (DHs), 13 regional hospitals and 4 tertiary hospitals were
      assessed. None of the CHCs could perform all seven BEmONC signal functions; the
      majority could not give parenteral antibiotics (68%), perform manual removal of
      the placenta (58%), do an assisted delivery (98%) or perform manual vacuum
      aspiration of the uterus in a woman with an uncomplicated incomplete miscarriage
      (96%). Seventeen per cent of CHCs could not bag-and-mask ventilate a neonate.
      Less than half (48%) of the DHs could perform all nine CEmONC signal functions
      (81% could perform eight of the nine functions), 24% could not perform caesarean
      sections, and 30% could not perform assisted deliveries. CONCLUSIONS: The ability
      of the CHCs and district hospitals to perform the signal functions (lifesaving
      services) of basic and comprehensive emergency obstetric care was poor in many of
      the districts studied. This implies that safe maternity care was not consistently
      available at many facilities conducting births.

PMID- 26294862
TI  - Safety versus accessibility in maternal and perinatal care.
AB  - This article adds to the debate on appropriate staffing in maternity units. My
      starting point for assessing staffing norms is the staff required to provide a
      safe maternity unit. A survey in 12 districts showed that their health facilities
      were not adequately prepared to perform all the essential emergency services
      required. Lack of staff was often cited as a reason. To test this notion, two
      norms (World Health Organization (WHO) and Greenfield) giving the minimum staff
      required for the provision of safe maternity services were applied to the 12
      districts. Assuming the appropriate equipment is available and the facility is
      open 24 hours a day 7 days a week, at a minimum there need to be ten professional
      nurses with midwifery/advanced midwives to ensure safety for mother and baby in
      every maternity unit. The norms indicate that the units should do a minimum of
      500-1,200 deliveries per year to be cost-effective. All 12 districts had
      sufficient staff according to the WHO. When the numbers of facilities with
      maternity units were compared with Council for Scientific and Industrial Research
      and WHO norms for number of health facilities per population, a large excess of
      facilities was found. Per district there were sufficient personnel to perform the
      number of deliveries for that district using the WHO or Greenfield formulas, but
      per site there were insufficient personnel. In my view there are sufficient
      personnel to provide safe maternity services, but too many units are performing
      deliveries, leading to dilution of staff and unsafe services. A realignment of
      maternity units must be undertaken to provide safe services, even at the expense
      of accessibility.

PMID- 26294863
TI  - Women's willingness to use emergency contraception: Experience at Chris Hani
      Baragwanath Academic Hospital, Johannesburg, South Africa.
AB  - Access to emergency contraception (EC) has little restriction in South Africa. EC
      is a contraceptive method that can be used by women up to 7 days after
      unprotected intercourse. It can be used in the following situations: when no
      contraceptive has been used; for condom accidents; after intrauterine
      contraceptive device expulsion; when a contraceptive method has been incorrectly
      used, or contraceptive pills missed; if there has been a > 3-hour delay in taking
      the progestogen-only pill, a > 2-week delay for intramuscular depot
      medroxyprogesterone acetate or a > 1-week delay for intramuscular norethisterone
      enanthate; or after delayed placement or early removal or dislodgement of a
      contraceptive transdermal patch or vaginal ring.

PMID- 26294864
TI  - Food insecurity in households in informal settlements in urban South Africa.
AB  - Food insecurity in the urban poor is a major public health challenge. The Health,
      Environment and Development study assessed trends in food insecurity and food
      consumption over a period of 7 years in an informal settlement in Johannesburg,
      South Africa (SA). Annual cross-sectional surveys were conducted in the informal
      settlement (Hospital Hill). The degree of household food insecurity decreased
      significantly from 2006 (85%) to 2012 (70%). There was a spike in 2009 (91%),
      possibly owing to global food price increases. Childhood food insecurity followed
      the same trend as household food insecurity. During the first 3 study years,
      consumption of protein, vegetables and fruit decreased by 10-20%, but had
      returned to previous levels by 2012. In this study, although declining, food
      insecurity remains unacceptably high. Hunger relief and poverty alleviation need
      to be more aggressively implemented in order to improve the quality of life in
      poor urban communities in SA.

PMID- 26294865
TI  - Oxytocin--ensuring appropriate use and balancing efficacy with safety.
AB  - Maternal deaths due to haemorrhage continue to increase in South Africa (SA). It
      appears that oxytocin and other uterotonics are not being used optimally, even
      though they are an essential part of managing maternal haemorrhage. Oxytocin
      should be administered to every mother delivering in SA. Awareness is required of
      the side-effects that can occur and the appropriate measures to avoid harm from
      these. Second-line uterotonics should also be available and utilised in
      conjunction with mechanical and surgical means to arrest haemorrhage in women who
      continue to bleed after the appropriate administration of oxytocin.

PMID- 26294866
TI  - MMed cohort supervision: A path out of the swamp?
AB  - The authors present the case for collaborative cohort supervision (CCM),
      including both master's students and novice supervisors, as a possible way to
      rapidly increase the number of supervisors needed to address the recent
      implementation of a compulsory research component to specialist registration with
      the Health Professions Council of South Africa. Different models of CCM are
      discussed and possible pitfalls highlighted.

PMID- 26294867
TI  - Resuscitating an ethical climate in the health system: The role of healthcare
      workers.
AB  - South Africa boasts a proud tradition of healthcare professionals speaking out
      against injustice in line with the medical doctrine of beneficence (to do good)
      and maleficence (do no harm). There are many who play a part in making the health
      system better, including the state, managers, patients and healthcare workers
      (HCWs). This article looks at the role of HCWs beyond providing medical care to
      individual patients. HCWs often face a lack of resources enabling them to
      adequately provide care and treatment and respond to life- threatening
      emergencies. As a result, they are forced to make difficult decisions when it
      comes to allocating those scarce resources. These decisions are not purely fiscal
      in nature, but also ethical. Deciding who to bump off a theatre list because
      there is no linen is a choice most HCWs did not imagine they would ever have to
      make. In order to circumvent a sense of hopelessness, HCWs need to empower and
      motivate themselves (and others) with knowledge of how to make things better.

PMID- 26294868
TI  - Traditional health practitioners and the authority to issue medical certificates.
AB  - The Interim Traditional Health Practitioners Council was inaugurated in February
      2013, and in May 2014 the sections of the Traditional Health Practitioners Act
      that give it full powers came into effect. The Council, as a professional body
      established by Parliament, gives traditional health practitioners registered with
      it the authority to issue medical certificates in line with the provisions of the
      Basic Conditions of Employment Act. However, the Council does not seem to be in a
      position to perform this function yet. Moreover, the field itself seems almost
      impossible to regulate because the practitioners cannot be subjected to objective
      assessment measures. While registered traditional health practitioners have the
      authority to issue medical certificates, it remains a moot point whether the
      certificates should be given full credibility before specific requirements for
      registration have been formulated and are implementable, and the envisaged code
      of conduct is in force.

PMID- 26294869
TI  - The HIV/HBV co-infected patient: Time for proactive management.

PMID- 26294870
TI  - Of ambivalence, shame and guilt: Perceptions regarding termination of pregnancy
      among South African women.

PMID- 26294871
TI  - Abuse in South African maternity settings is a disgrace: Potential solutions to
      the problem.

PMID- 26294872
TI  - Maternal death and caesarean section in South Africa: Results from the 2011-2013
      Saving Mothers Report of the National Committee for Confidential Enquiries into
      Maternal Deaths.
AB  - BACKGROUND: In the latest (2011-2013) Saving Mothers report, the National
      Committee for Confidential Enquiries into Maternal Deaths in South Africa (SA)
      (NCCEMD) highlights the large number of maternal deaths associated with caesarean
      section (CS). The risk of a woman dying as a result of CS during the past
      triennium was almost three times that for vaginal delivery. Of all the mothers
      who died during or after a CS, 3.4% died during the procedure and 14.5% from
      haemorrhage afterwards. Including all cases of death from obstetric haemorrhage
      where a CS was done, there were 5.5 deaths from haemorrhage for every 10,000 CSs
      performed. OBJECTIVE: To scrutinise the contribution or effect of the surgical
      procedure on the ultimate cause of death by a cross-cutting analysis of the 2011
      2013 national data. METHODS: Data from the 2011-2013 triennial review were
      entered into an Excel database and analysed on a national and provincial basis.
      RESULTS: There were 1,243 maternal deaths where a CS was the mode of delivery and
      1 471 deaths after vaginal delivery. More mothers died as a result of CS in the
      provinces where there is a low overall CS rate. The following CS categories were
      identified as specific problems: bleeding during or after CS, pre-eclampsia and
      eclampsia, anaesthesia-related deaths, pregnancy-related sepsis and acute
      collapse and embolism. CONCLUSION: This is an area of concern, and a concentrated
      effort should be done to make CS in SA safer. Several recommendations are

PMID- 26294873
TI  - Utility of the Robson Ten Group Classification System to determine
      appropriateness of caesarean section at a rural regional hospital in KwaZulu
      Natal, South Africa.
AB  - BACKGROUND: High caesarean section (CS) rates are not only costly but associated
      with significant perinatal and maternal morbidity and mortality. It has recently
      been suggested that structured auditing of CSs may identify those groups in the
      obstetric population that contribute substantially to the high rates and for
      which focused interventions may bring about change. OBJECTIVE: To evaluate the
      utility of the Robson Ten Group Classification System (RTGCS) in determining
      appropriateness of CS at a regional rural hospital in KwaZulu-Natal Province,
      South Africa. METHODS: A retrospective review of the hospital records of women
      delivered by CS over a 3-month period was performed. The RTGCS was used to
      categorise women according to parity, age, past obstetric history, singleton or
      multiple pregnancy, fetal presentation, gestational age and mode of onset of
      labour/delivery. RESULTS: There were 2 553 hospital births over the 3-month study
      period. The CS rate was 42.4% (1 082/2 553). According to the RTGCS, groups 1 (n
      = 296, 27.4%), 5 (n = 186, 17.2%) and 10 (n = 253, 23.4%) were substantial
      contributors to the overall CS rate. The main indications for CS were fetal
      distress (36.5%) and cephalopelvic disproportion (26.8%). CONCLUSION: The RTGCS
      is a useful tool with which to identify patient groups warranting interventions
      to reduce high CS rates in a rural regional hospital setting. Group 1 (nullipara:
      single cephalic term pregnancy; spontaneous labour) warrants the most attention.
      Applying stricter criteria and due diligence in decision-making for primary CS
      may decrease the high CS rates.

PMID- 26294874
TI  - Office-based sperm concentration: A simplified method for intrauterine
      insemination therapy.
AB  - BACKGROUND: Intrauterine insemination (IUI) could become preferred to more
      invasive and expensive techniques of assisted reproduction therapy (ART) and
      should be offered as the first choice in cases with no female factors and mild
      male factor subfertility. However, developing countries and especially their
      rural areas often lack the necessary equipment and laboratory facilities.
      OBJECTIVE: To describe a simplified one-step method to determine the sperm
      concentration range for IUI therapy. METHODS: Semen samples from 51 sperm donors
      were used. Following swim-up separation, the sperm concentration of the retrieved
      motile fraction was counted, as well as progressive motile sperm using a
      standardised wet preparation. The number of sperm in a 10 uL droplet covered with
      a 22 x 22 mm coverslip was counted under 400 x total magnification. The observed
      numbers of retrieved motile sperm were divided into three groups: < 40, 40-100
      and > 101 spermatozoa as recorded per intial estimation on the wet preparation.
      RESULTS: The mean (standard deviation) estimated sperm concentration for each
      group compared with actual counts per Neubauer counting chamber were: estimated <
      40 sperm (n = 14), mean 20 (8), Neubauer count 2.5 x 10(6)/mL; estimated 40-100
      sperm (n = 14), mean 71 (15), Neubauer count 16 x 10(6)/mL; and estimated > 100
      sperm (n = 23), Neubauer count 48.3 (21.7) x 10(6)/mL. CONCLUSION: The results
      with IUI in male subfertility cases reported by Ombelet et al. in 1995 support
      the concept of first-line treatment of infertility by three to four cycles of IUI
      therapy in selected cases.

PMID- 26294875
TI  - Intrapartum asphyxia and hypoxic ischaemic encephalopathy in a public hospital:
      Incidence and predictors of poor outcome.
AB  - OBJECTIVE: To determine the incidence of asphyxia and hypoxic ischaemic
      encephalopathy (HIE) and predictors of poor outcome in a hospital in a developing
      country. METHODS: Neonates of birth weight >= 2,000 g who required bag-and-mask
      ventilation and were admitted with a primary diagnosis of asphyxia from January
      to December 2011 were included. Medical records were retrieved and maternal and
      infant data collected and analysed. Infants who had severe HIE and/or died were
      compared with those who survived to hospital discharge with no or mild to
      moderate HIE. RESULTS: There were 21 086 liveborn infants with a birth weight of
      2 000 g over the study period. The incidence of asphyxia ranged from 8.7 to
      15.2/1 000 live births and that of HIE from 8.5 to 13.3/1 000, based on the
      definition of asphyxia used. In 60% of patients with HIE it was moderate to
      severe. The overall mortality rate was 7.8%. The mortality rate in infants with
      moderate and severe HIE was 7.1% and 62.5%, respectively. The odds of severe HIE
      and/or death were high if the Apgar score was <5 at 10 minutes (odds ratio (OR)
      19.1; 95% confidence interval (CI) 5.7-66.9) and if there was no spontaneous
      respiration at 20 minutes (OR 27.2; 95% CI 6.9-117.4), a need for adrenaline (OR
      81.2; 95% CI 13.2-647.7) and a pH of < 7 (OR 5.33; 95% CI 1.31-25.16). Predictors
      of poor outcome were Apgar score at 10 minutes (p = 0.004), need for adrenaline
      (p = 0.034) and low serum bicarbonate (p = 0.028). CONCLUSION: The incidence of
      asphyxia in term and near-term infants is higher than that reported in developed
      countries. Apgar score at 10 minutes and need for adrenaline remain important
      factors in predicting poor outcome in infants with asphyxia.

PMID- 26294876
TI  - Pathological findings in reduction mammoplasty specimens: A South African
      perspective.
AB  - BACKGROUND: Preoperative, intraoperative and follow-up guidelines for managing
      occult carcinoma in reduction mammoplasty specimens are scant METHODS: We
      retrospectively analysed the records and pathology reports of 200 patients who
      had undergone reduction mammoplasty at two major public hospitals in
      Johannesburg, South Africa, during 2009-2014. Demographic data, their history of
      breast cancer and preoperative screening, the surgical techniques used and
      pathological reports were included. In all cases preoperative screening for
      breast cancer had been negative. RESULTS: All the patients were female, mean age
      37.1 years, range 20-84 (standard deviation 11.9). All reductions were performed
      using standard techniques. Benign pathology was observed in 98 patients (49%) and
      malignant pathology in four (2%). The most common benign pathology observed was
      fibrocystic disease, and the most common malignant pathology ductal carcinoma in
      situ. Patient age correlated significantly with benign or malignant disease.
      CONCLUSIONS: Reduction mammoplasty produces tissue that should always be sent for
      pathological assessment. Patients should be stratified by risk, as doing so helps
      in selecting both the surgical setting and the approach to pathological analysis
      of the specimen. While the incidence of occult carcinoma in reduction mammoplasty
      specimens is low, all patients undergoing the procedure should be informed that
      tissue will be sent for pathological examination, allowing them to prepare to
      receive possible news of breast cancer and be adequately equipped for subsequent
      decision-making.

PMID- 26294877
TI  - Comparison of findings using ultrasonography and cystoscopy in urogenital
      schistosomiasis in a public health centre in rural Angola.
AB  - BACKGROUND: Schistosomiasis is a chronic disease caused by infection with
      parasitic worms of the genus Schistosoma. In sub-Saharan Africa, infections with
      S. haematobium are most common. Cystoscopic examination (CE) has been accepted as
      the goldstandard test for detecting the late manifestations of schistosomiasis,
      including urothelial cancer of the bladder. However, this procedure is invasive
      and 10-40% of tumours may remain undetected. A non-invasive examination and a new
      generation of biomarkers are needed for better monitoring of the disease.
      OBJECTIVE: To assess the usefulness of ultrasound (US) scans for monitoring of
      structural urinary tract disease by local public health services in areas of
      Angola in which urogenital schistosomiasis is endemic. METHODS: A cohort of 80 S.
      haematobium-infected patients was selected in order to compare changes in the
      bladder wall detected by US with those observed on CE. RESULTS: There was a
      notable correlation between the findings observed on CE and US. Patients with
      lesions of the bladder mucosa such as neoplasms, ulcers or granulomas detected by
      CE also had changes in bladder wall thickness on US. The results support
      increased use of portable US machines for non-invasive examination of the bladder
      by local general practitioners. CONCLUSION: US examination should be an integral
      part of the investigation of haematuria and used in all S. haematobium control
      programmes. General practitioners may find it useful for more accurate diagnosis
      of haematuria and to identify bladder wall alterations in both adults and
      children in schistosomiasis-endemic regions.

PMID- 26294878
TI  - Paediatric chronic kidney disease.
AB  - Doctors use various guidelines on paediatric chronic kidney disease (CKD) for
      managing their patients according to the availability of resources. As with
      adolescent and adult patients, CKD in children can also progress to end-stage
      renal failure - the time course being influenced by several modifiable factors.
      Decline in renal failure is best categorised in stages, which determine
      management and prognosis. Staging is based on three categories, i.e. cause,
      glomerular filtration rate and proteinuria. Early diagnosis of CKD allows for the
      institution of renoprotective treatment of modifiable factors and treatment to
      prevent the development of complications. The two most important modifiable
      factors that can be treated successfully are hypertension and proteinuria. The
      objective of this article is to provide information on the diagnosis and
      treatment of CKD in children. Early identification and treatment of modifiable
      risk factors of CKD decreases the burden of disease and delays or prevents the
      need for renal replacement therapy.

PMID- 26294880
TI  - Medical ethics and human rights in wartime.

PMID- 26294881
TI  - Community paediatrics and child health.

PMID- 26294883
TI  - Max Klein, 1941-2015.

PMID- 26294886
TI  - Containing contraceptive costs.

PMID- 26294887
TI  - Chronic kidney disease.
AB  - In his review article in the March 2015 edition ofCME, Prof. A M Meyers refers to
      chronic kidneydisease as 'an important disease group that threatenshealth'. I
      fully concur with this observation andwish to go a step further and assert that
      kidneydisease, together with other related non-communicable diseases(NCDs), poses
      not only a threat to health but also to theoverall development of South Africa
      (SA). It is now almost 4 yearssince the adoption of the Political Declaration of
      the High-levelMeeting of the General Assembly on the Prevention and Controlof Non
      communicable Diseases (September 2011), where itwas emphatically stated that
      member States that have signed theDeclaration (including SA) 'Acknowledge that
      the global burdenand threat of non-communicable diseases constitutes one of
      themajor challenges for development in the twenty-first century,which undermines
      social and economic development throughoutthe world, and threatens the
      achievement of internationallyagreed development goals'.

PMID- 26294888
TI  - Important causes of chronic kidney disease in South Africa.
AB  - In hypertensive patients without chronic kidney disease (CKD) the goal is to keep
      blood pressure (BP) at <=140/90 mmHg. When CKD ispresent, especially where there
      is proteinuria of >=0.5 g/day, the goal is a BP of <=130/80 mmHg. Lifestyle
      measures are mandatory, especiallylimitation of salt intake, ingestion of
      adequate quantities of potassium, and weight control. Patients with stages 4 - 5
      CKD must be carefullymonitored for hyperkalaemia and deteriorating kidney
      function if angiotensin-converting enzyme (ACE) inhibitors or angiotensin
      IIreceptor blockers (ARBs) are used, especially in patients >60 years of age with
      diabetes or atherosclerosis. BP should be regularly monitoredand, where possible,
      home BP-measuring devices are recommended for optimal control.Guidelines on the
      use of antidiabetic agents in CKD are presented, with the warning that metformin
      is contraindicated in patients withstages 4 - 5 CKD.There is a wide clinical
      spectrum of renal disease in the course of HIV infection, including acute kidney
      injury, electrolyte and acid-basedisturbances, HIV-associated glomerular disease,
      acute-on-chronic renal disease and side-effects related to the treatment of HIV.

PMID- 26294889
TI  - Important complications of chronic kidney disease.
AB  - The complications of chronic kidney disease (CKD) are dyslipidaemia,
      hyperkalaemia, metabolic acidosis, anaemia, and bone and mineraldisorders.
      Dyslipidaemia may be treated with low-density lipoprotein-lowering agents.
      Statins are ineffective in stages 4 and 5 CKD, but areindicated for preventing
      the progression of disease in the earlier stages. Chronic acidosis has recently
      been shown to be a risk factor in theprogression of CKD renal dysfunction.
      Therefore, treatment is mandatory. Practically, this should consist of 1 - 2
      heaped teaspoons of sodiumbicarbonate 2 - 3 times per day, which is an
      inexpensive and safe therapy that does not raise the blood pressure in spite of
      the increased sodiumlevel. Target levels of haemoglobin, according to
      international guidelines, are between 10 g/dL and 12 g/dL. The serum phosphate
      level is raisedin stage 4 CKD, and especially in stage 5 CKD, which is associated
      with coronary carotid and other vascular calcifications and may result
      inischaemic heart disease, myocardial infarction and stroke. A raised parathyroid
      hormone level (secondary hyperparathyroidism) is also a majorrisk factor for
      cardiovascular disease and is associated with increased hypertension and
      resistance to the treatment of CKD-associated anaemia.

PMID- 26294891
TI  - List of contributors to the articles and information compiled by the National
      Kidney Foundation of South Africa.

PMID- 26294890
TI  - Drugs and the kidney.
AB  - This article on drug nephrotoxicity is detailed, as it is important to be fully
      aware of renal side-effects of drugs with regard to prevention andearly diagnosis
      in order to manage the condition correctly. Many therapeutic agents are
      nephrotoxic, particularly when the serum half-life isprolonged and blood levels
      are raised because of decreased renal excretion. Distal nephrotoxicity is
      markedly enhanced when the glomerularfiltration rate (GFR) is reduced and is a
      particular threat in elderly patients with so-called 'normal' creatinine levels.
      In patients of 45 - 55 years of age theGFR is reduced by about 1 mL/min/year, so
      that an otherwise healthy person of 80 may have an estimated GFR (eGFR) of <60
      mL/min or <50 mL/min,i.e. stage 2, 3 or 3b chronic kidney disease (CKD).
      Furthermore, other effects related to kidney dysfunction may be seen, e.g.
      worsening of hypertensionwith the use of non-steroidal anti-inflammatory drugs,
      increased bruising or bleeding tendency with aspirin, and hyponatraemia
      hypertensionacidosis with angiotensin-converting enzyme inhibitors or angiotensin
      II receptor blockers. Digoxin is contraindicated in stage 3 CKD, even ina reduced
      dosage. Other drugs can cause the direct formation of kidney stones, e.g.
      topiramate (used in the prophylaxis of resistant migraine).Levofloxacin (Tavanic)
      can cause rupture of the Achilles tendon and other tendons.Radiocontrast media
      must be used with care. Occasionally, strategies to prevent acute kidney
      insufficiency cause irreversible CKD,especially in patients with diabetes and
      those with myeloma who have stage 4 - 5 CKD. Gadolinium in its many forms (even
      the newerproducts) used as contrast medium for magnetic resonance imaging is best
      avoided in patients with stages 4 and 5 CKD.

PMID- 26294892
TI  - CPD Questions.

PMID- 26294893
TI  - Reliability and Validity of the Dutch Translation of the Filial Maturity Measure
      in Informal Caregivers.
AB  - This study explored the reliability and validity of a Dutch translation of the 10
      item Filial Maturity Measure (FMM) in a sample of Dutch informal caregivers. The
      FMM was translated with a forward-backward method and completed by 93 informal
      caregivers (62 % response rate) with a need dependent parent. Dimensionality of
      the Dutch FMM was examined by principal component and internal consistency
      analyses. Criterion validity was examined by assessing correlations with filial
      love, filial autonomy and level of closeness between parent and child. Construct
      validity was tested by examining associations with the traits openness and
      agreeableness. In addition, the relationship with state and trait affectivity was
      explored. After removal of the item "I worry about turning out like my parent",
      the original dimensional structure, internal consistency, criterion and construct
      validity were confirmed. Additional exploration of the relation between the FMM
      subscales and trait and state affectivity scales demonstrated that filial
      maturity is at most weakly associated with trait affectivity. Both FMM scales
      showed a positive partial correlation with negative state affectivity. The Dutch
      FMM appears to be a reliable and valid instrument for measuring filial maturity
      of informal caregivers who provide care to their need dependent parent. The (non
      )functioning of one item pointed to the necessity to validate the FMM, but also
      questionnaires in general in different populations.

PMID- 26294894
TI  - Using Mindfulness- and Acceptance-Based Treatments With Clients From Nondominant
      Cultural and/or Marginalized Backgrounds: Clinical Considerations, Meta-Analysis
      Findings, and Introduction to the Special Series.
AB  - A growing body of research suggests that mindfulness- and acceptance-based
      principles can increase efforts aimed at reducing human suffering and increasing
      quality of life. A critical step in the development and evaluation of these new
      approaches to treatment is to determine the acceptability and efficacy of these
      treatments for clients from nondominant cultural and/or marginalized backgrounds.
      This special series brings together the wisdom of clinicians and researchers who
      are currently engaged in clinical practice and treatment research with
      populations who are historically underrepresented in the treatment literature. As
      an introduction to the series, this paper presents a theoretical background and
      research context for the papers in the series, highlights the elements of
      mindfulness- and acceptance-based treatments that may be congruent with
      culturally responsive treatment, and briefly outlines the general principles of
      cultural competence and responsive treatment. Additionally, the results of a meta
      analysis of mindfulness- and acceptance-based treatments with clients from
      nondominant cultural and/or marginalized backgrounds are presented. Our search
      yielded 32 studies totaling 2,198 clients. Results suggest small (Hedges' g=.38,
      95% CI=.11 - .64) to large (Hedges' g=1.32, 95% CI=.61 - 2.02) effect sizes for
      mindfulness- and acceptance-based treatments, which varied by study design.

PMID- 26294895
TI  - Researching the researcher-as-instrument: an exercise in interviewer self
      reflexivity.
AB  - Because the researcher is the instrument in semistructured or unstructured
      qualitative interviews, unique researcher characteristics have the potential to
      influence the collection of empirical materials. This concept, although widely
      acknowledged, has garnered little systematic investigation. This article
      discusses the interviewer characteristics of three different interviewers who are
      part of a qualitative research team. The researcher/interviewers - and authors of
      this article - reflect on their own and each other's interviews and explore the
      ways in which individual interview practices create unique conversational spaces.
      The results suggest that certain interviewer characteristics may be more
      effective than others in eliciting detailed narratives from respondents depending
      on the perceived sensitivity of the topic, but that variation in interviewer
      characteristics may benefit rather than detract from the goals of team-based
      qualitative inquiry. The authors call for the inclusion of enhanced self
      reflexivity in interviewer training and development activities and argue against
      standardization of interviewer practices in qualitative research teams.

PMID- 26294896
TI  - Introduction to the Special Issue.

PMID- 26294897
TI  - Perceptions and Concerns Regarding Diabetes Mellitus During Pregnancy Among
      American Indian Women.
AB  - Diabetes among American Indian (AI) people is a. condition that creates excessive
      morbidity and mortality and is a significant health disparity. This research
      delineated culturally constructed models of diabetes mellitus (DM) among 97
      pregnant women in 2 large AI Nations to Oklahoma. Analysis of data revealed
      intense anxiety, fear, and dread related to DM during pregnancy. The sample was
      stratified by DM status: (a) absence of DM (n = 66), (b) DM prior to pregnancy (n
      = 4), and (c) gestational (n = 27). Structured and semistructured interviews
      elicited patient culturally based explanatory models (EMs) of etiology, course,
      and treatment. The research incorporated an integrated phenomenologic and
      ethnographic approach and yielded both quantitative and qualitative data. General
      findings comprised the following main categories of patients' concerns regarding
      DM as an illness: (a) care-seeking behaviors, (b) medical management, (c)
      adherence and self-management, (d) complications, and (e) the conceptual sense of
      DM as a "severe" and feared condition. Many findings varied according to
      acculturation status, but all included significant fear and anxiety surrounding
      (a) the health and well-being of the unborn child, (b) the use of insulin
      injections, (c) blindness, (d) amputation, and (e) death, but with (f) a
      paradoxically lowered anxiety level about diabetes severity overall, while at the
      same time expressing extreme dread of specific outcomes. The latter finding is
      considered consistent with the presence of chronic conditions that can usually be
      managed, yet still having risk if severe.

PMID- 26294898
TI  - A Survey of Self-Management and Intrusiveness of Illness in Native Americans with
      Diabetes Mellitus.
AB  - Diabetes mellitus (DM) has emerged as an important focus of national public
      health efforts because of the rapid increase in the burden of this disease. In
      particular, DM disproportionately affects Native Americans. Adequate management
      of DM requires that patients participate as active partners in their own care and
      much of patient activation and empowerment can be attributed to their experience
      with DM and self-care. That is, the degree to which the patient feels the disease
      intrudes on his or her daily life would impact the motivation for self-care. We
      conducted a study in collaboration with 2 tribal nations in Oklahoma, collecting
      data on survey questions regarding intrusiveness of illness and self-management
      behaviors from a sample of 159 members of the Chickasaw and Choctaw Nations.
      Previously validated variables measuring intrusiveness of illness and self-care
      were included in the survey. Descriptive statistics and bivariate analyses
      illustrated the distribution of these variables and identified possible tribal
      and gender differences. Our findings showed that our sample adjusted well to DM
      and in general exhibited high compliance to self-care. However, our findings also
      revealed striking gender differences where female respondents were better
      adjusted to their disease, whereas male respondents reported higher adherence to
      self-management. Findings from our study, particularly those that describe tribal
      differences and gender disparities, can inform strategies for case management and
      patient interactions with providers and the health care system.

PMID- 26294900
TI  - American Indian Diabetes Prevention Center: Challenges of a Health Equity Quest.
AB  - American Indians are classified by the federal government as a "health
      disparities population" with significant excess morbidity and mortality caused by
      diabetes and its many complications. The National Institute on Minority Health
      and Health Disparities of the National Institutes of Health has created a
      national program titled "Centers of Excellence" whose primary goal is the
      elimination of health disparities. This article describes the American Indian
      Diabetes Prevention Center at the University of Oklahoma Health Sciences Center,
      College of Public Health, in terms of its intellectual foundations rooted in a
      biocultural analytic model and operationalized by an interdisciplinary
      functioning staff. Challenges are described in terms of the monumental task of
      impacting health disparity conditions and in the exigencies of research
      collaborations with American Indian Nations located in rural areas remote to the
      University's health sciences urban-based hub.

PMID- 26294901
TI  - Synthesis and Characterization with Antineoplastic, Biochemical, Cytotoxic, and
      Antimicrobial Studies of Schiff Base Cu(II) Ion Complexes.
AB  - Copper(II) complexes containing two Schiff base ligands derived from 2
      hydroxybenzaldehyde with 2-aminophenol and 3-aminophenol have been synthesized
      and characterized by means of analytical, magnetic, and spectroscopic methods.
      Bacteria, fungus, Entamoeba histolytica, and antineoplastic activities of the
      synthesized complexes have been determined by monitoring the parameters cell
      growth inhibition, survival time of tumour mice, time-body relation, causing of
      intraperitoneal cells and macrophages, alkaline phosphatase activity,
      hematological effect, and biopsy of tumour. 

PMID- 26294902
TI  - Paenibacillus panaciterrae sp. nov., isolated from ginseng-cultivated soil.
AB  - A novel bacterium, designated DCY95T, was isolated from ginseng-cultivated soil
      in Quang Nam province, Vietnam. On the basis of 16S rRNA and gyrB gene sequence
      analysis, this isolate was assigned to the genus Paenibacillus and found to be
      closely related to Paenibacillus sacheonensis SY01T (97.1 % 16S rRNA gene
      sequence similarity) and Paenibacillus taihuensis THMBG22T (96.4 %). The partial
      gyrB gene of DCY95T possessed 69.6-83.9 % sequence identity to those of other
      members of the genus Paenibacillus. Strain DCY95T was Gram-reaction-negative,
      catalase-negative, oxidase-positive, strictly aerobic, rod-shaped and motile by
      means of peritrichous flagella. Ellipsoidal free spores or subterminal endospores
      were produced in sporangia. MK-7 was the diagnostic menaquinone. The cell-wall
      peptidoglycan contained meso-diamonopimelic acid as the diamino acid. Whole-cell
      sugars comprised ribose, mannose and glucose. The major cellular fatty acids were
      anteiso-C15 : 0, iso-C16 : 0 and C16 : 0. The major polar lipids were
      phosphatidylethanolamine, phosphatidylglycerol, three unidentified
      aminophospholipids, and two unidentified phospholipids. The genomic DNA G+C
      content was 60.7 +/- 0.9 mol%. Phenotypic and chemotaxonomic results placed
      strain DCY95T within the genus Paenibacillus. However, DNA-DNA relatedness values
      between strain DCY95T and P. sacheonensis KACC 14895T or P. taihuensis NBRC
      108766T were lower than 36 %. The low DNA relatedness data in combination with
      phylogenetic and (GTG)5-PCR analyses, as well as biochemical tests, indicated
      that strain DCY95T could not be assigned to any recognized species. In
      conclusion, the results in this study support the classification of strain DCY95T
      as a representative of a novel species within the genus Paenibacillus, for which
      the name Paenibacillus panaciterrae is proposed. The type strain is DCY95T ( =
      KCTC 33581T = DSM 29477T).

PMID- 26294899
TI  - Weight-Bearing Exercise and Foot Health in Native Americans.
AB  - Diabetes contributes to sensory peripheral neuropathy, which has been linked to
      lower limb abnormalities that raise the risk for foot ulcers and amputations.
      Because amputations are a reason for pain and hospitalization in those with
      diabetes, it is of critical importance to gain insight about prevention of ulcer
      development in this population. Although the American Diabetes Association (ADA)
      now recommends that individuals with neuropathy can engage in moderate-intensity
      weight-bearing activity (WBA), they must wear appropriate footwear and inspect
      their feet daily. The physical forces and inflammatory processes from WBA may
      contribute to plantar characteristics that lead to ulcers. The purpose of this
      study was to compare neuropathic status and foot characteristics in Native
      Americans according to WBA classification. The t tests for unequal sample sizes
      found that exercisers had more difficulty sensing baseline temperature than
      nonexercisers, except at the right foot (all p values < .05). By dividing groups
      into no/low risk and high risk for ulcer, a majority showed no/low risk according
      to touch and vibration sense. Exercisers demonstrated higher surface skin
      temperature gradients at the first metatarsal head, a plantar site where wounds
      tend to form. The more consistently exercisers performed, the higher the plan-tar
      pressures were at the right second (r = .24, p = .02) and third metatarsal heads
      (r = .26, p = .01). Findings from this investigation do not refute current ADA
      recommendations and further intervention studies are needed that are longitudinal
      and measures WBA more accurately.

PMID- 26294903
TI  - Dynamic Bus Travel Time Prediction Models on Road with Multiple Bus Routes.
AB  - Accurate and real-time travel time information for buses can help passengers
      better plan their trips and minimize waiting times. A dynamic travel time
      prediction model for buses addressing the cases on road with multiple bus routes
      is proposed in this paper, based on support vector machines (SVMs) and Kalman
      filtering-based algorithm. In the proposed model, the well-trained SVM model
      predicts the baseline bus travel times from the historical bus trip data; the
      Kalman filtering-based dynamic algorithm can adjust bus travel times with the
      latest bus operation information and the estimated baseline travel times. The
      performance of the proposed dynamic model is validated with the real-world data
      on road with multiple bus routes in Shenzhen, China. The results show that the
      proposed dynamic model is feasible and applicable for bus travel time prediction
      and has the best prediction performance among all the five models proposed in the
      study in terms of prediction accuracy on road with multiple bus routes. 

PMID- 26294904
TI  - Psychometrics of the Greek Chronic Liver Disease Questionnaire for Measuring
      HRQL.
AB  - The aim of the present study is to examine psychometric properties such as
      internal consistency reliability and construct validity of the Greek CLDQ. A
      sample of 366 eligible patients with chronic liver disease (CLD) self
      administered the Greek version of the SF-36 Health Survey, the Chronic Liver
      Disease Questionnaire (CLDQ), and questions on sociodemographic status and
      treatment. Child Pugh Score was also collected. Hypothesized scale structure,
      reliability (Cronbach's alpha), and construct validity (convergent, discriminant,
      and known groups) were assessed. Multitrait scaling confirmed scale structure of
      the CLDQ with good item convergence (100%) and discrimination (84.1%) rates.
      Cronbach's alpha rated >0.70 for all scales. Spearman's correlations between the
      CLDQ and SF-36 scales assessing similar health-related quality of life dimensions
      were strong ranging above 0.70 (P < 0.0001). Construct validity was confirmed
      with satisfactory results for known-group comparisons. Most CLDQ scales
      discriminated significantly between patients according to disease severity,
      whereas all CLDQ scales discriminated between treatment receivers and
      nonreceivers. The overall psychometric results for the Greek version of the CLDQ
      confirmed it as a reliable and valid questionnaire. 

PMID- 26294905
TI  - Serum Syndecan-1 Levels and Its Relationship to Disease Activity in Patients with
      Crohn's Disease.
AB  - Background. Syndecan-1 (SDC-1), a member of the family of heparan sulfate
      proteoglycans, plays an important role in the resolution of inflammation. This
      study aimed to investigate the relationship between SDC-1 and disease activity in
      Crohn's disease (CD). Methods. Serum samples of 54 patients with CD and 30
      healthy controls were obtained. First, SDC-1 levels of the CD patients were
      compared to the control group. Subsequently, SDC-1 levels were analyzed in
      patients with CD in active and remission periods. Finally, SDC-1 efficacy in
      predicting disease activity was evaluated by performing correlation analysis
      between SDC-1 and C-reactive protein (CRP) and Crohn's disease activity index
      (CDAI). Results. SDC-1 level was higher in the CD group (61.9 +/- 42.6 ng/mL)
      compared with the control group (34.1 +/- 8.0 ng/mL) (p = 0.03). SDC-1 levels
      were higher in active CD patients (97.1 +/- 40.3 ng/mL) compared with those in
      remission (33.7 +/- 13.5 ng/mL) (p < 0.001). A significant positive correlation
      was found between SDC-1 and CRP (r = 0.687, p < 0.001) and between SDC-1 and CDAI
      (r = 0.747, p < 0.001). Conclusion. Serum levels of SDC-1 are higher in CD
      compared to the normal population and can be an effective marker of disease
      severity. 

PMID- 26294906
TI  - Menopausal Symptoms and Its Correlates: A Study on Tribe and Caste Population of
      East India.
AB  - Present study aimed to compare the incidence of menopausal problems and
      concomitants between tribe and caste population. This cross section study was
      conducted in five villages of West Bengal, a state in the eastern part of India.
      This study was conducted between two different ethnic groups-one of the
      "Particularly Vulnerable Tribal Groups (PTG)" of India named as "Lodha" and the
      other was a Bengali speaking caste population. A total number of 313 participants
      were finally recruited for this study. Study participants were married, had at
      least one child, had no major gynaecological problems, and had stopped menstrual
      bleeding spontaneously for at least 1 year. Additionally, data on
      sociodemographic status and menstrual and reproductive history were collected
      using a pretested questionnaire/schedule. Bivariate analyses (chi square test)
      revealed that significantly more number of caste participants suffered from
      urinary problems than their tribe counterpart. The reverse trend has been noticed
      for the frequency of vaginal problems. Multivariate analyses (binary logistic
      regression) show that sociodemographic variables and menstrual and reproductive
      history of the present study participants seem to be the concomitants of
      menopausal symptoms. Tribe and caste study population significantly differed with
      respect to the estrogen deficient menopausal problems and the concomitants to
      these problems. 

PMID- 26294908
TI  - Beneficial Effects of the mTOR Inhibitor Everolimus in Patients with Advanced
      Medullary Thyroid Carcinoma: Subgroup Results of a Phase II Trial.
AB  - Objective. Until recently, advanced medullary thyroid cancer (MTC) had few
      treatment options except surgery. The mTOR inhibitor everolimus has shown
      encouraging results in neuroendocrine tumors. As part of a prospective phase II
      study, we analyzed the safety and efficacy of everolimus in advanced MTC.
      Methods. Seven patients with per RECIST 1.1 documented advanced MTC were included
      and received everolimus 10 mg daily. The primary objective was determining
      treatment efficacy. Secondary endpoints included progression-free survival (PFS),
      overall survival (OS), toxicity, and pharmacokinetics (PK). Results. Median
      follow-up duration was 28 weeks (17-147). Five patients (71%) showed SD, of which
      4 (57%) showed SD >24 weeks. Median PFS and OS were 33 (95%CI: 8-56) and 30
      (95%CI: 15-45) weeks, respectively. Toxicity was predominantly grade 1/2 and
      included mucositis (43%), fatigue (43%), and hypertriglyceridemia (43%). Four
      MTCs harbored the somatic RET mutation c.2753T>C, p.Met918Thr. The best clinical
      response was seen in a MEN2A patient. PK characteristics were consistent with
      phase I data. One patient exhibited extensive toxicity accompanying elevated
      everolimus plasma concentrations. Conclusions. This study suggests that
      everolimus exerts clinically relevant antitumor activity in patients with
      advanced MTC. Given the high level of clinical benefit and the relatively low
      toxicity profile, further investigation of everolimus in these patients is
      warranted. 

PMID- 26294909
TI  - Alpha-Lipoic Acid Attenuates Cerebral Ischemia and Reperfusion Injury via Insulin
      Receptor and PI3K/Akt-Dependent Inhibition of NADPH Oxidase.
AB  - Alpha-lipoic acid (ALA) has various pharmacological effects such as
      antioxidative, anti-inflammatory, and antiapoptotic properties. In the present
      study, administration of ALA (40 mg/kg, i.p.) for 3 days resulted in a
      significant decrease in neuronal deficit score and infarct volume and a
      significant increase in grip time and latency time in Morris water maze at 48 h
      after middle cerebral artery occlusion and reperfusion (MCAO/R) in rats. ALA also
      reduced the increased TUNEL-positive cells rate and the enhanced caspase-3
      activity induced by MCAO/R. However, the underlying mechanisms remain poorly
      understood. In this study, we found that ALA could activate insulin receptor and
      PI3K/Akt signaling pathways, inhibit the expression and activity of NADPH
      oxidase, and subsequently suppress the generation of superoxide and the augment
      of oxidative stress indicators including MDA, protein carbonylation, and 8-OHdG.
      In conclusion, ALA attenuates cerebral ischemia and reperfusion injury via
      insulin receptor and PI3K/Akt-dependent inhibition of NADPH oxidase. 

PMID- 26294907
TI  - Succinate Dehydrogenase Loss in Familial Paraganglioma: Biochemistry, Genetics,
      and Epigenetics.
AB  - It is counterintuitive that metabolic defects reducing ATP production can cause,
      rather than protect from, cancer. Yet this is precisely the case for familial
      paraganglioma, a form of neuroendocrine malignancy caused by loss of succinate
      dehydrogenase in the tricarboxylic acid cycle. Here we review biochemical,
      genetic, and epigenetic considerations in succinate dehydrogenase loss and
      present leading models and mysteries associated with this fascinating and
      important tumor. 

PMID- 26294910
TI  - Practical Advice for Emergency IUD Contraception in Young Women.
AB  - Too few women are aware of the very high efficacy of intrauterine copper devices
      (IUDs) to prevent pregnancy after unprotected intercourse. Women who frequently
      engage in unprotected intercourse or seek emergency contraception (EC) are at
      high risk of unplanned pregnancy and possible abortion. It is therefore important
      that these women receive precise and accurate information about intrauterine
      devices as they may benefit from using an IUD for EC as continuing contraception.
      Copper IUDs should be used as first choice options given their rapid onset of
      action and their long-term contraceptive action which require minimal thought or
      intervention on the part of the user. In the United States, there is only one
      copper IUD presently available which limits treatment options. There are numerous
      copper IUDs available for use in EC, however, their designs and size are not
      always optimal for use in nulliparous women or women with smaller or narrower
      uteruses. Utilization of frameless IUDs which do not require a larger transverse
      arm for uterine retention may have distinct advantages, particularly in young
      women, as they will be suitable for use in all women irrespective of uterine
      size. This paper provides practical information on EC use with emphasis on the
      use of the frameless IUD. 

PMID- 26294911
TI  - Aurantimicrobium minutum gen. nov., sp. nov., a novel ultramicrobacterium of the
      family Microbacteriaceae, isolated from river water.
AB  - A Gram-stain-positive, aerobic, non-motile, curved (selenoid), rod-shaped
      actinobacterium, designated KNCT, was isolated from the 0.2 MUm-filtrate of river
      water in western Japan. Cells of strain KNCT were ultramicrosized (0.04-0.05
      MUm3). The strain grew at 15-37  degrees C, with no observable growth at 10 
      degrees C or 40  degrees C. The pH range for growth was 7-9, with weaker growth
      at pH 10. Growth was impeded by the presence of NaCl at concentrations greater
      than 1 %. Phylogenetic analysis based on 16S rRNA gene sequences revealed that
      strain KNCT showed relatively high sequence similarity (97.2 %) to Alpinimonas
      psychrophila Cr8-25T in the family Microbacteriaceae. However, strain KNCT formed
      an independent cluster with cultured, but as-yet-unidentified, species and
      environmental clones on the phylogenetic tree. The major cellular fatty acids
      were anteiso-C15 : 0 (41.0 %), iso-C16 : 0 (21.8 %), C16 : 0 (18.0 %) and anteiso
      C17 : 0 (12.9 %), and the major menaquinones were MK-11 (71.3 %) and MK-12 (13.6
      %). The major polar lipids were phosphatidylglycerol and two unknown glycolipids.
      The cell-wall muramic acid acyl type was acetyl. The peptidoglycan was B-type,
      and contained 3-hydroxyglutamic acid, glutamic acid, aspartic acid, glycine,
      alanine and lysine, with the latter being the diagnostic diamino acid. The G+C
      content of the genome was unusually low for actinobacteria (52.1 mol%), compared
      with other genera in the family Microbacteriaceae. Based on the phenotypic
      characteristics and phylogenetic evidence, strain KNCT represents a novel species
      of a new genus within the family Microbacteriaceae, for which the name
      Aurantimicrobium minutum gen. nov., sp. nov. is proposed. The type strain of the
      type species is KNCT ( = NBRC 105389T = NCIMB 14875T).

PMID- 26294912
TI  - Baclofen-Induced Encephalopathy in End Stage Renal Disease.
AB  - Baclofen is a highly used centrally acting GABA agonist that continues to be an
      effective therapy for spasticity and chronic hiccups. The renally dependent
      excretion determines the circulating concentrations and guides effective dosing
      to decrease adverse reactions. Caution should be considered in administering
      baclofen to patients with decreased renal function. We present a patient with end
      stage renal disease on hemodialysis with recent baclofen ingestion who presented
      with toxic encephalopathy that was resolved with additional dialysis sessions. 

PMID- 26294913
TI  - Histopathologic Finding of Both Gastric and Respiratory Epithelia in a Lingual
      Foregut Cyst.
AB  - Foregut cysts are uncommon, mucosa-lined congenital lesions that may occur
      anywhere along the gastrointestinal or respiratory tract and typically present
      within the first year of life. Although infrequent, these cysts may generate
      feeding or respiratory difficulties depending on the size and location of the
      lesion. Foregut cysts of the oral cavity are rarely seen and of those cases
      localized to the tongue are even more uncommon. We describe a 4-month-old girl
      with a foregut cyst involving the floor of mouth and anterior tongue. Subsequent
      histologic analysis demonstrated a cyst lined with both gastric and respiratory
      epithelia. This case represents an extremely rare finding of both gastric and
      respiratory epithelia lined within a single cystic structure in the tongue.
      Although a very rare finding, a foregut cyst should be on the differential
      diagnosis of any lesion involving the floor of mouth or tongue in an infant or
      child. 

PMID- 26294914
TI  - Laparoscopic Sleeve Gastrectomy in a Morbidly Obese Patient with Myasthenia
      Gravis: A Review of the Management.
AB  - Myasthenia gravis, a disorder of neuromuscular transmission, presents a unique
      challenge to the perioperative anesthetic management of morbidly obese patients.
      This report describes the case of a 27-year-old morbidly obese woman with a past
      medical history significant for myasthenia gravis and fatty liver disease
      undergoing bariatric surgery. Anesthesia was induced with intravenous agents and
      maintained with an inhalational and balanced intravenous technique. The
      nondepolarizing neuromuscular blocker Cisatracurium was chosen so that no
      reversal agents were given. Neostigmine was not used to antagonize the effects of
      Cisatracurium. The goal of this approach was to reduce the risk of complications
      such as postoperative mechanical ventilation. The anesthetic and surgical
      techniques used resulted in an uneventful hospital course. Therefore, we can
      minimize perioperative risks and complications by adjusting the anesthetic plan
      based on the patient's physiology and comorbidities as well as the pharmacology
      of the drugs. 

PMID- 26294915
TI  - First Case of Tricuspid Valve Endocarditis Caused by Gemella bergeri.
AB  - Gemella bergeri is a Gram-positive cocci species arranged in pairs and composes
      the normal flora of oral cavity, digestive and urinary tract. Several species of
      Gemella are known to cause endocarditis. Here, we report the first case in
      Thailand of G. bergeri endocarditis whose blood culture was negative using
      routine methods but was positive by PCR identification of bacteria in the
      affected valve. A 37-year-old male presented with prolonged fever, weight loss,
      and dyspnea on exertion. By transthoracic echocardiography, he was suspected of
      having infective endocarditis of the tricuspid valve. The patient underwent
      tricuspid valve repair and vegetectomy. Routine hospital blood cultures were
      negative but G. bergeri was identified by PCR/sequencing of the heart valve
      tissue. 

PMID- 26294916
TI  - MSCs: Scientific Support for Multiple Therapies.

PMID- 26294917
TI  - Comparisons of Differentiation Potential in Human Mesenchymal Stem Cells from
      Wharton's Jelly, Bone Marrow, and Pancreatic Tissues.
AB  - Background. Type 1 diabetes mellitus results from autoimmune destruction of beta
      cells. Insulin-producing cells (IPCs) differentiated from mesenchymal stem cells
      (MSCs) in human tissues decrease blood glucose levels and improve survival in
      diabetic rats. We compared the differential ability and the curative effect of
      IPCs from three types of human tissue to determine the ideal source of cell
      therapy for diabetes. Methods. We induced MSCs from Wharton's jelly (WJ), bone
      marrow (BM), and surgically resected pancreatic tissue to differentiate into
      IPCs. The in vitro differential function of these IPCs was compared by insulin-to
      DNA ratios and C-peptide levels after glucose challenge. In vivo curative effects
      of IPCs transplanted into diabetic rats were monitored by weekly blood glucose
      measurement. Results. WJ-MSCs showed better proliferation and differentiation
      potential than pancreatic MSCs and BM-MSCs. In vivo, WJ-IPCs significantly
      reduced blood glucose levels at first week after transplantation and maintained
      significant decrease till week 8. BM-IPCs reduced blood glucose levels at first
      week but gradually increased since week 3. In resected pancreas-IPCs group, blood
      glucose levels were significantly reduced till two weeks after transplantation
      and gradually increased since week 4. Conclusion. WJ-MSCs are the most promising
      stem cell source for beta-cell regeneration in diabetes treatment. 

PMID- 26294918
TI  - The Cotransplantation of Olfactory Ensheathing Cells with Bone Marrow Mesenchymal
      Stem Cells Exerts Antiapoptotic Effects in Adult Rats after Spinal Cord Injury.
AB  - The mechanisms behind the repairing effects of the cotransplantation of olfactory
      ensheathing cells (OECs) with bone marrow mesenchymal stromal cells (BMSCs) have
      not been fully understood. Therefore, we investigated the effects of the
      cotransplantation of OECs with BMSCs on antiapoptotic effects in adult rats for
      which the models of SCI are induced. We examined the changes in body weight,
      histopathological changes, apoptosis, and the expressions of apoptosis-related
      proteins after 14 days and 28 days after transplantation. We also assessed animal
      locomotion using BBB test. We found that treatment with OECs and BMSCs had a
      remissive effect on behavioral outcome and histopathological changes induced SCI.
      Furthermore, we observed the significant antiapoptotic effect on cotransplant
      treated group. In addition, cotransplantation of OECs with BMSCs was found to
      have more significant repairing effect than that of OECs or BMSCs alone.
      Furthermore, the recovery of hind limb could be related to antiapoptotic effect
      of OECs and BMSCs through downregulating the apoptotic pathways. Finally, our
      data suggested the cotransplantation of OECs with BMSCs holds promise for a
      potential cure after SCI through the ability to incorporate into the spinal cord.

PMID- 26294919
TI  - Mesenchymal Stromal Cells and Viral Infection.
AB  - Mesenchymal Stromal Cells (MSCs) are a subset of nonhematopoietic adult stem
      cells, readily isolated from various tissues and easily culture-expanded ex vivo.
      Intensive studies of the immune modulation and tissue regeneration over the past
      few years have demonstrated the great potential of MSCs for the prevention and
      treatment of steroid-resistant acute graft-versus-host disease (GvHD), immune
      related disorders, and viral diseases. In immunocompromised individuals, the
      immunomodulatory activities of MSCs have raised safety concerns regarding the
      greater risk of primary viral infection and viral reactivation, which is a major
      cause of mortality after allogeneic transplantation. Moreover, high
      susceptibilities of MSCs to viral infections in vitro could reflect the
      destructive outcomes that might impair the clinical efficacy of MSCs infusion.
      However, the interplay between MSCs and virus is like a double-edge sword, and it
      also provides beneficial effects such as allowing the proliferation and function
      of antiviral specific effector cells instead of suppressing them, serving as an
      ideal tool for study of viral pathogenesis, and protecting hosts against viral
      challenge by using the antimicrobial activity. Here, we therefore review
      favorable and unfavorable consequences of MSCs and virus interaction with the
      highlight of safety and efficacy for applying MSCs as cell therapy. 

PMID- 26294920
TI  - Physiological Age Structure and Leishmania spp. Detection in Phlebotomus
      (Larroussius) orientalis (Parrot, 1936) (Diptera: Psychodidae) at an Endemic
      Focus of Visceral Leishmaniasis in Northern Ethiopia.
AB  - Visceral leishmaniasis (VL) caused by Leishmania donovani is endemic in northern
      Ethiopia, where P. orientalis is the most important presumed vector. This study
      was designed to determine the physiological age structure and the occurrence of
      Leishmania infection in the vector of VL in Tahtay Adiyabo district, northern
      Ethiopia. Sand flies were collected using CDC light traps from peridomestic and
      agricultural fields between May 2011 and April 2012 and P. orientalis females
      were dissected for age determination and detection of Leishmania promastigotes.
      Sand flies were also analyzed for L. donovani detection using molecular methods.
      Of 1,282 P. orientalis examined for abdominal stages and age characterization,
      66.2%, 28.2%, 4.1%, and 1.6% were unfed, freshly fed, half-gravid, and gravid.
      Parous rate in unfed females was 34.1% and 35.4% in peridomestic and agricultural
      fields, respectively. Out of 921 P. orientalis females dissected, one specimen
      (0.1%) was found naturally infected with promastigotes. Five pools (25 females)
      of unfed P. orientalis were also found with DNA of Leishmania spp. In particular,
      a single P. orientalis was positive for L. donovani (0.5%). Based on this and
      other evidences (abundance, human blood feeding, and xenodiagnostic studies), P.
      orientalis is the principal vector of VL in this endemic focus. 

PMID- 26294921
TI  - Influences of Deqi on Immediate Analgesia Effect of Needling SP6 (Sanyinjiao) in
      Patients with Primary Dysmenorrhea in Cold and Dampness Stagnation Pattern: Study
      Protocol for a Randomized Controlled Trial.
AB  - Deqi, according to traditional Chinese medicine, is a specific needle sensation
      during the retention of needles at certain acupoints and is considered to be
      necessary to produce therapeutic effects from acupuncture. Although some modern
      researches have showed that Deqi is essential for producing acupuncture analgesia
      and anesthesia, the data are not enough. It is a paper of a multicenter,
      randomized controlled study protocol, to evaluate the influences of Deqi on
      acupuncture SP6 in Cold and Dampness Stagnation pattern primary dysmenorrhea
      patients, in terms of reducing pain and anxiety, and to find out the relationship
      between Deqi and the temperature changes at SP6 (Sanyinjiao) and CV4 (Guanyuan).
      The results of this trial will be helpful to explain the role of Deqi in
      acupuncture analgesia and may provide a new objective index for measuring Deqi in
      the future study. This trial is registered with ChiCTR-TRC-13003086. 

PMID- 26294922
TI  - Discovery of Acupoints and Combinations with Potential to Treat Vascular
      Dementia: A Data Mining Analysis.
AB  - The prevalence of vascular dementia (VaD) is high among the elderly. Acupuncture,
      a popular therapeutic method in China, can improve memory, orientation,
      calculation, and self-managing ability in VaD patients. However, in clinical
      acupuncture and acupuncture research, the selection of acupoints to treat VaD
      remains challenging. This study aimed to discover acupoints and acupoint
      combinations with potential for VaD based on data mining. After database
      searching and screening for articles on clinical trials evaluating the effects of
      acupuncture on VaD, 238 acupuncture prescriptions were included for further
      analysis. Baihui (GV 20), Sishencong (EX-HN 1), Fengchi (GB 20), Shuigou (GV 26),
      and Shenting (GV 24) appeared most frequently in the modern literature and are
      potential acupoints for VaD. Combinations between Baihui (GV 20), Sishencong (EX
      HN 1), Fengchi (GB 20), Shenting (GV 24), Shuigou (GV 26), and Zusanli (ST 36)
      were most frequent and represent potential combinations for VaD treatment. These
      results provide a reference for the selection and combination of acupoints to
      treat VaD in clinical acupuncture and acupuncture research. 

PMID- 26294923
TI  - Electroacupuncture versus Moxibustion for Irritable Bowel Syndrome: A Randomized,
      Parallel-Controlled Trial.
AB  - Objective. To compare the impacts of electroacupuncture (EA) and mild moxibustion
      (Mox) on patients with irritable bowel syndrome (IBS). Method. Eighty-two IBS
      patients were randomly allocated into EA group (n = 41) and Mox group (n = 41)
      and received corresponding interventions for four weeks. Before and after the
      treatment, the Visual Analogue Scale for Irritable Bowel Syndrome (VAS-IBS) was
      used to evaluate the gastrointestinal symptoms and mental well-being; and the
      expression of serotonin (5-hydroxytryptamine, 5-HT), 5-HT3 receptor (5-HT3R), and
      5-HT4 receptor (5-HT4R) in sigmoid mucosal tissue were detected. Results. Both EA
      and Mox can radically improve the total VAS-IBS score (P < 0.05), and EA was
      found to be more effective in ameliorating the symptom of constipation, while Mox
      was found to be more effective in ameliorating the symptom of diarrhoea. The
      abnormal expressions of 5-HT, 5-HT3R, and 5-HT4R in both groups were
      significantly improved after the treatments (all P < 0.05), and EA was superior
      to Mox in regulating the abnormally decreased 5-HT4R expression in IBS patients
      with constipation (P < 0.05). Conclusion. Electroacupuncture and mild moxibustion
      were both effective in improving IBS symptoms and modulate abnormal expressions
      of 5-HT, 5-HT3R, and 5-HT4R in the colonic tissue. 

PMID- 26294925
TI  - Traditional Chinese Medicine and Autonomic Disorders.

PMID- 26294924
TI  - miRNA Regulation Network Analysis in Qianliening Capsule Treatment of Benign
      Prostatic Hyperplasia.
AB  - Objective. The objective of this study was to evaluate the molecular mechanism by
      which Qianliening capsule (QC) treats benign prostatic hyperplasia (BPH).
      Methods. Benign prostatic hyperplasia epithelial cell line BPH-1 was treated with
      0, 1.25, 2.5, and 5 mg/mL QC for 48 h, respectively. Evaluation of cell viability
      and observation of morphologic changes of BPH-1 cell gene expression and miRNA
      expression profiles were analyzed. Real-time quantitative PCR was used to confirm
      changes in miRNA and gene expression. GO and KEGG pathway-based approaches were
      used to investigate biological functions and signaling pathways affected by
      differentially expressed mRNAs. Results. QC inhibited BPH-1 cell proliferation.
      Differential expression of 19 upregulated and 2 downregulated miRNAs was observed
      in QC-treated BPH-1 cells compared to untreated control cells. 107 upregulated
      and 71 downregulated genes were identified between the two groups. Significantly
      enriched signaling pathways based on deregulated mRNAs were mainly involved in
      regulation of cell proliferation, apoptosis, and so on. Additionally, miRNA-mRNA
      network analysis integrated these miRNAs and genes by outlining interactions of
      miRNA and related genes. Conclusion. The study was the first report of
      differentially expressed miRNA and mRNA in QC-treated BPH-1 cells. 

PMID- 26294926
TI  - Hair Growth Promotion Activity and Its Mechanism of Polygonum multiflorum.
AB  - Polygonum multiflorum Radix (PMR) has long history in hair growth promotion and
      hair coloring in clinical applications. However, several crucial problems in its
      clinic usage and mechanisms are still unsolved or lack scientific evidences. In
      this research, C57BL/6J mice were used to investigate hair growth promotion
      activity and possible mechanism of PMR and Polygonum multiflorum Radix Preparata
      (PMRP). Hair growth promotion activities were investigated by hair length, hair
      covered skin ratio, the number of follicles, and hair color. Regulation effects
      of several cytokines involved in the hair growth procedure were tested, such as
      fibroblast growth factor (FGF-7), Sonic Hedgehog (SHH), beta-catenin, insulin
      like growth factor-1 (IGF-1), and hepatocyte growth factor (HGF). Oral PMR groups
      had higher hair covered skin ratio (100 +/- 0.00%) than oral PMRP groups
      (48%~88%). However, topical usage of PMRP had about 90% hair covered skin ratio.
      Both oral administration of PMR and topically given PMRP showed hair growth
      promotion activities. PMR was considered to be more suitable for oral
      administration, while PMRP showed greater effects in external use. The hair
      growth promotion effect of oral PMR was most probably mediated by the expression
      of FGF-7, while topical PMRP promoted hair growth by the stimulation of SHH
      expression. 

PMID- 26294927
TI  - A Lindera obtusiloba Extract Blocks Calcium-/Phosphate-Induced
      Transdifferentiation and Calcification of Vascular Smooth Muscle Cells and
      Interferes with Matrix Metalloproteinase-2 and Metalloproteinase-9 and NF-kappaB.
AB  - Vascular calcifications bear the risk for cardiovascular complications and have a
      high prevalence among patients with chronic kidney disease. Central mediators of
      vascular calcifications are vascular smooth muscle cells (VSMC). They
      transdifferentiate into a synthetic/osteoblast-like phenotype, which is induced,
      for example, by elevated levels of calcium and phosphate (Ca/P) due to a
      disturbed mineral balance. An aqueous extract from Lindera obtusiloba (LOE) is
      known to exert antifibrotic and antitumor effects or to interfere with the
      differentiation of preadipocytes. Using murine and rat VSMC cell lines, we here
      investigated whether LOE also protects VSMC from Ca/P-induced calcification.
      Indeed, LOE effectively blocked Ca/P-induced calcification of VSMC as shown by
      decreased VSMC mineralization and secretion of alkaline phosphatase. In parallel,
      mRNA expression of the calcification markers osterix and osteocalcin was reduced.
      Vice versa, the Ca/P-induced loss of the VSMC differentiation markers alpha
      smooth muscle actin and smooth muscle protein 22-alpha was rescued by LOE.
      Further, LOE blocked Ca/P-induced mRNA expressions and secretions of matrix
      metalloproteinases-2/-9 and activation of NF-kappaB, which are known contributors
      to vascular calcification. In conclusion, LOE interferes with the Ca/P-induced
      transdifferentiation/calcification of VSMC. Thus, LOE should be further analysed
      regarding a potential complementary treatment option for cardiovascular diseases
      including vascular calcifications. 

PMID- 26294928
TI  - Preliminary Evidence That Yoga Practice Progressively Improves Mood and Decreases
      Stress in a Sample of UK Prisoners.
AB  - Objectives. In the first randomized controlled trial of yoga on UK prisoners, we
      previously showed that yoga practice was associated with improved mental
      wellbeing and cognition. Here, we aimed to assess how class attendance, self
      practice, and demographic factors were related to outcome amongst prisoners
      enrolled in the 10-week yoga intervention. Methods. The data of 55 participants
      (52 male, 3 female) who completed a 10-week yoga course were analysed. Changes in
      pre- and postyoga measures of affect, perceived stress, and psychological
      symptoms were entered into linear regression analyses with bias-corrected and
      accelerated bootstrap confidence intervals. Class attendance, self-practice,
      demographic variables, and baseline psychometric variables were included as
      regressors. Results. Participants who attended more yoga classes and those who
      engaged in frequent (5 times or more) self-practice reported significantly
      greater decreases in perceived stress. Decreases in negative affect were also
      significantly related to high frequency self-practice and greater class
      attendance at a near-significant level. Age was positively correlated with yoga
      class attendance, and higher levels of education were associated with greater
      decreases in negative affect. Conclusions. Our results suggest that there may be
      progressive beneficial effects of yoga within prison populations and point to
      subpopulations who may benefit the most from this practice. 

PMID- 26294929
TI  - Traditional Uses, Phytochemistry, and Bioactivities of Cananga odorata (Ylang
      Ylang).
AB  - Ylang-ylang (Cananga odorata Hook. F. & Thomson) is one of the plants that are
      exploited at a large scale for its essential oil which is an important raw
      material for the fragrance industry. The essential oils extracted via steam
      distillation from the plant have been used mainly in cosmetic industry but also
      in food industry. Traditionally, C. odorata is used to treat malaria, stomach
      ailments, asthma, gout, and rheumatism. The essential oils or ylang-ylang oil is
      used in aromatherapy and is believed to be effective in treating depression, high
      blood pressure, and anxiety. Many phytochemical studies have identified the
      constituents present in the essential oils of C. odorata. A wide range of
      chemical compounds including monoterpene, sesquiterpenes, and phenylpropanoids
      have been isolated from this plant. Recent studies have shown a wide variety of
      bioactivities exhibited by the essential oils and the extracts of C. odorata
      including antimicrobial, antibiofilm, anti-inflammatory, antivector, insect
      repellent, antidiabetic, antifertility and antimelanogenesis activities. Thus,
      the present review summarizes the information concerning the traditional uses,
      phytochemistry, and biological activities of C. odorata. This review is aimed at
      demonstrating that C. odorata not only is an important raw material for perfume
      industry but also considered as a prospective useful plant to agriculture and
      medicine. 

PMID- 26294930
TI  - Acupuncture for Functional Dyspepsia: A Single Blinded, Randomized, Controlled
      Trial.
AB  - In order to investigate the therapeutic potential of acupuncture on patients with
      functional dyspepsia (FD), patients were randomized to receive acupuncture at
      classic acupoints with manipulations (treatment group) versus acupuncture at
      nonacupoints without manipulation (control group) once every other day, three
      times a week, for one month and were followed up for three months. The primary
      outcomes included dyspeptic symptoms, quality of life, and mental status. The
      secondary outcomes included the fasting serum gastrin concentration, and
      frequency and propagation velocity of gastric slow waves. Sixty patients with FD
      were included, among whom, four dropped out. After one month's treatment,
      patients with FD showed significant improvements in primary (in both groups) and
      secondary (in the eight patients of the treatment group) outcomes as compared
      with baseline (P = 0.0078 to <0.0001); treatment group has better outcomes in all
      primary outcome measures (P < 0.0001 except for SDS (P = 0.0005)). Improvements
      on dyspeptic symptoms persist during follow-up (better in the treatment group).
      Acupuncture with manual manipulation had better effects on improving dyspeptic
      symptoms, mental status, and quality of life in patients with FD. These effects
      may be related to the increased frequency and propagation speed of gastric slow
      waves and serum gastrin secretion. 

PMID- 26294931
TI  - Muricauda pacifica sp. nov., isolated from seawater of the South Pacific Gyre.
AB  - A Gram-stain-negative, strictly aerobic, non-flagellated, non-gliding, oxidase-
      and catalase-positive, rod-shaped and orange-pigmented bacterium with appendages,
      designated strain SW027T, was isolated from a surface seawater sample collected
      from the South Pacific Gyre (26 degrees  29' S 137 degrees  56' W) during the
      Integrated Ocean Drilling Program (IODP) Expedition 329. Phylogenetic analysis
      based on 16S rRNA gene sequences indicated that strain SW027T shared the highest
      sequence similarity with members of the genus Muricauda (94.3-92.7 %), exhibiting
      94.3 % sequence similarity to Muricauda flavescens SW-62T. Optimal growth
      occurred in the presence of 3 % (w/v) NaCl, at pH 7.0 and at 37  degrees C. The
      DNA G+C content of strain SW027T was 42.7 mol%. The major fatty acids were iso
      C15 : 0, iso-C15 : 1 G and iso-C17 : 0 3-OH. The major respiratory quinone was
      menaquinone-6. The major polar lipids were phosphatidylethanolamine and two
      unidentified lipids. Enzymic activity profiles, cell morphology and DNA G+C
      content differentiated the novel bacterium from the most closely related members
      of the genus Muricauda. On the basis of the polyphasic analyses, strain SW027T is
      considered to represent a novel species of the genus Muricauda, for which the
      name Muricauda pacifica sp. nov. is proposed. The type strain is SW027T ( = JCM
      17861T = LMG 26637T).

PMID- 26294932
TI  - Local discrepancies in continental scale biomass maps: a case study over forested
      and non-forested landscapes in Maryland, USA.
AB  - BACKGROUND: Continental-scale aboveground biomass maps are increasingly
      available, but their estimates vary widely, particularly at high resolution. A
      comprehensive understanding of map discrepancies is required to improve their
      effectiveness in carbon accounting and local decision-making. To this end, we
      compare four continental-scale maps with a recent high-resolution lidar-derived
      biomass map over Maryland, USA. We conduct detailed comparisons at pixel-, county
      , and state-level. RESULTS: Spatial patterns of biomass are broadly consistent in
      all maps, but there are large differences at fine scales (RMSD 48.5-92.7 Mg ha
      1). Discrepancies reduce with aggregation and the agreement among products
      improves at the county level. However, continental scale maps exhibit residual
      negative biases in mean (33.0-54.6 Mg ha-1) and total biomass (3.5-5.8 Tg) when
      compared to the high-resolution lidar biomass map. Three of the four continental
      scale maps reach near-perfect agreement at ~4 km and onward but do not converge
      with the high-resolution biomass map even at county scale. At the State level,
      these maps underestimate biomass by 30-80 Tg in forested and 40-50 Tg in non
      forested areas. CONCLUSIONS: Local discrepancies in continental scale biomass
      maps are caused by factors including data inputs, modeling approaches, forest/non
      forest definitions and time lags. There is a net underestimation over high
      biomass forests and non-forested areas that could impact carbon accounting at all
      levels. Local, high-resolution lidar-derived biomass maps provide a valuable
      bottom-up reference to improve the analysis and interpretation of large-scale
      maps produced in carbon monitoring systems.

PMID- 26294933
TI  - Machine learning classifiers provide insight into the relationship between
      microbial communities and bacterial vaginosis.
AB  - BACKGROUND: Bacterial vaginosis (BV) is a disease associated with the vagina
      microbiome. It is highly prevalent and is characterized by symptoms including
      odor, discharge and irritation. No single microbe has been found to cause BV. In
      this paper we use random forests and logistic regression classifiers to model the
      relationship between the microbial community and BV. We use subsets of the
      microbial community features in order to determine which features are important
      to the classification models. RESULTS: We find that models generated using
      logistic regression and random forests perform nearly identically and identify
      largely similar important features. Only a few features are necessary to obtain
      high BV classification accuracy. Additionally, there appears to be substantial
      redundancy between the microbial community features. CONCLUSIONS: These results
      are in contrast to a previous study in which the important features identified by
      the classifiers were dissimilar. This difference appears to be the result of
      using different feature importance measures. It is not clear whether machine
      learning classifiers are capturing patterns different from simple correlations.

PMID- 26294934
TI  - Rheumatic heart disease among adults in a mining community of Papua, Indonesia:
      findings from an occupational cohort.
AB  - BACKGROUND: Rheumatic heart disease (RHD) remains a significant cause of
      cardiovascular morbidity and mortality in developing countries such as Indonesia.
      Yet, despite being one of the most readily preventable chronic diseases, RHD has
      received scant research or policy attention, particularly in South-East Asia.
      AIM: To describe the pattern of RHD occurrence in a sample of presenting cases
      from an occupational cohort in Papua Province, Indonesia. METHODS: Clinical
      records of 15 608 mining workers (96.4% men, mean age 36.3+/-7.4 years) were
      reviewed retrospectively to identify and extract data on all rheumatic fever (RF)
      and RHD cases admitted to two hospitals in Papua during 2008-2013. Collected data
      included basic demographics, employment history and echocardiographic findings.
      RESULTS: 83 RHD cases (95.6% men, mean age 39.6+/-12.5 years) and 3 RF cases were
      identified between 2008 and 2013. Increased RHD risk was observed among those
      aged 35-44 (HR=3.60) and 45-68 (HR=4.46) years relative to the youngest age group
      (p<0.01). RHD incidence density was 6.84 per 10 000 person years of follow-up.
      Among cases, mitral stenosis was the most common valvular lesion at initial
      presentation (41.0%), and 6.0% were multivalvular. CONCLUSIONS: The prevalence of
      RHD in Papuan mining workers correlates with adult prevalence data in other
      populations with a high RHD burden, highlighting RHD as a significant health
      issue into adulthood. The late stage at which most patients presented points to a
      strong need for earlier intervention. Both primary and secondary preventive
      measures must be considered critical tools to prevent and reduce RHD burden,
      particularly among older age groups.

PMID- 26294935
TI  - Thalassocola ureilytica gen. nov., sp. nov., of the family Phyllobacteriaceae
      isolated from seawater.
AB  - A Gram-stain-negative, aerobic, rod-shaped, non-flagellated marine bacterium,
      designated strain LS-861T, was isolated from seawater of the South China Sea
      (Taiwan). Strain LS-861T grew optimally at pH 7.0 and 30  degrees C in the
      presence of 3 % (w/v) NaCl. The novel strain shared highest 16S rRNA gene
      sequence similarity (91.5 % each) with 'Nitratireductor shengliensis' CGMCC
      1.12519 and Hoeflea halophila JG120-1T and lower sequence similarity ( < 91.5 %)
      with other species. Phylogenetic analyses based on 16S rRNA gene sequences
      revealed a distinct taxonomic position attained by strain LS-861T within the
      clade that accommodated members of the family Phyllobacteriaceae. The major fatty
      acids were C16 : 0, iso-C17 : 1omega10c, C18 : 0 3-OH and C18 : 1omega7c/C18 :
      1omega6c. The polar lipid profile was relatively simple as compared with other
      representatives of Phyllobacteriaceae, by having major amounts of
      diphosphatidylglycerol, phosphatidylglycerol and an unidentified glycolipid, and
      moderate amounts of three unidentified phospholipids and an unidentified
      aminolipid. The DNA G+C content was 61.2 mol%. The predominant quinone system was
      ubiquinone-10 (Q-10). The data in general and phylogenetic and polar lipid data
      in particular clearly distinguish the novel strain from related species at the
      genus level. Thus, strain LS-861T is suggested to represent a novel species of a
      new genus of the family Phyllobacteriaceae, for which the name Thalassocola
      ureilytica gen. nov., sp. nov. is proposed. The type strain of Thalassocola
      ureilytica is LS-861T ( = BCRC 80818T = JCM 30682T).

PMID- 26294936
TI  - Why Some Humanoid Faces Are Perceived More Positively Than Others: Effects of
      Human-Likeness and Task.
AB  - Ample research in social psychology has highlighted the importance of the human
      face in human-human interactions. However, there is a less clear understanding of
      how a humanoid robot's face is perceived by humans. One of the primary goals of
      this study was to investigate how initial perceptions of robots are influenced by
      the extent of human-likeness of the robot's face, particularly when the robot is
      intended to provide assistance with tasks in the home that are traditionally
      carried out by humans. Moreover, although robots have the potential to help both
      younger and older adults, there is limited knowledge of whether the two age
      groups' perceptions differ. In this study, younger (N = 32) and older adults (N =
      32) imagined interacting with a robot in four different task contexts and rated
      robot faces of varying levels of human-likeness. Participants were also
      interviewed to assess their reasons for particular preferences. This multi-method
      approach identified patterns of perceptions across different appearances as well
      as reasons that influence the formation of such perceptions. Overall, the results
      indicated that people's perceptions of robot faces vary as a function of robot
      human-likeness. People tended to over-generalize their understanding of humans to
      build expectations about a human-looking robot's behavior and capabilities.
      Additionally, preferences for humanoid robots depended on the task although
      younger and older adults differed in their preferences for certain humanoid
      appearances. The results of this study have implications both for advancing
      theoretical understanding of robot perceptions and for creating and applying
      guidelines for the design of robots.

PMID- 26294937
TI  - Where are the food deserts? An evaluation of policy-relevant measures of
      community food access in South Carolina.
AB  - Several recent United States (US) policies target spatial access to healthier
      food retailers. We evaluated two measures of community food access developed by
      two different agencies, using a 2009 food environment validation study in South
      Carolina as a reference. While the US Department of Agriculture Economic Research
      Service's (USDA ERS) measure designated 22.5% of census tracts as food deserts,
      the Centers for Disease Control and Prevention's (CDC) measure designated 29.0%
      as non-healthier retail tracts; 71% of tracts were designated consistently
      between USDA ERS and CDC. Our findings suggest a need for greater harmonization
      of these measures of community food access.

PMID- 26294938
TI  - Reactive Oxygen Species in Stem Cells.

PMID- 26294940
TI  - Redefining Quality in Medical Education Research: A Consumer's View.
AB  - BACKGROUND: Despite an explosion of medical education research and publications,
      it is not known how medical educator consumers decide what to read or apply in
      their practice. OBJECTIVE: To determine how consumers of medical education
      research define quality and value. METHODS: Journal of Graduate Medical Education
      editors performed a literature search to identify articles on medical education
      research quality published between 2000 and 2013, surveyed medical educators for
      their criteria for judging quality, and led a consensus-building workshop at a
      2013 Association of American Medical Colleges meeting to further explore how
      users defined quality in education research. The workshop used standard consensus
      building techniques to reach concept saturation. Attendees then voted for the 3
      concepts they valued most in medical education research. RESULTS: The 110 survey
      responses generated a list of 37 overlapping features in 10 categories considered
      important aspects of quality. The literature search yielded 27 articles,
      including quality indexes, systematic and narrative reviews, and commentaries.
      Thirty-two participants, 12 facilitators, and 1 expert observer attended the
      workshop. Participants endorsed the following features of education research as
      being most valuable: (1) provocative, novel, or challenged established thinking;
      (2) adhered to sound research principles; (3) relevant to practice, role, or
      needs; (4) feasible, practical application in real-world settings; and (5)
      connection to a conceptual framework. CONCLUSIONS: Medical educators placed high
      value on rigorous methods and conceptual frameworks, consistent with published
      quality indexes. They also valued innovative or provocative work, feasibility,
      and applicability to their setting. End-user opinions of quality may illuminate
      how educators translate knowledge into practice.

PMID- 26294939
TI  - Mitochondrial Respiratory Chain Inhibitors Involved in ROS Production Induced by
      Acute High Concentrations of Iodide and the Effects of SOD as a Protective
      Factor.
AB  - A major source of reactive oxygen species (ROS) generation is the mitochondria.
      By using flow cytometry of the mitochondrial fluorescent probe, MitoSOX Red,
      western blot of mitochondrial ROS scavenger Peroxiredoxin (Prx) 3 and
      fluorescence immunostaining, ELISA of cleaved caspases 3 and 9, and TUNEL
      staining, we demonstrated that exposure to 100 MUM KI for 2 hours significantly
      increased mitochondrial superoxide production and Prx 3 protein expression with
      increased expressions of cleaved caspases 3 and 9. Besides, we indicated that
      superoxide dismutase (SOD) at 1000 unit/mL attenuated the increase in
      mitochondrial superoxide production, Prx 3 protein expression, and lactate
      dehydrogenase (LDH) release and improved the relative cell viability at 100 MUM
      KI exposure. However, SOD inhibitor diethyldithiocarbamic acid (DETC) (2 mM),
      Rotenone (0.5 MUM), a mitochondrial complex I inhibitor, and Antimycin A (10
      MUM), a complex III inhibitor, caused an increase in mitochondrial superoxide
      production, Prx 3 protein expression, and LDH release and decreased the relative
      cell viability. We conclude that the inhibitors of mitochondrial respiratory
      chain complex I or III may be involved in oxidative stress caused by elevated
      concentrations of iodide, and SOD demonstrates its protective effect on the
      Fischer rat thyroid cell line (FRTL) cells. 

PMID- 26294942
TI  - Previous Acute Polio and Post-Polio Syndrome: Recognizing the Pathophysiology for
      the Establishment of Rehabilitation Programs.

PMID- 26294941
TI  - Similar Effects of Two Modified Constraint-Induced Therapy Protocols on Motor
      Impairment, Motor Function and Quality of Life in Patients with Chronic Stroke.
AB  - Modified constraint-induced movement therapy (CIMT) protocols show motor function
      and real-world arm use improvement. Meanwhile it usually requires constant
      supervision by physiotherapists and is therefore more expensive than customary
      care. This study compared the preliminary efficacy of two modified CIMT
      protocols. A two-group randomized controlled trial with pre and post treatment
      measures and six months follow-up was conducted. Nineteen patients with chronic
      stroke received 10 treatment sessions distributed three to four times a week over
      22 days. CIMT3h_direct group received 3 hours of CIMT supervised by a therapist
      (n=10) while CIMT1.5h_direct group had 1.5 hours of supervised CIMT+1.5 hours
      home exercises supervised by a caregiver (n=9). Outcome measures were the Fugl
      Meyer Assessment, the Motor Activity Log, and the Stroke Specific Quality of Life
      Scale. The modified CIMT protocols were feasible and well tolerated. Improvements
      in motor function, real-world arm use and quality of life did not differ
      significantly between treated groups receiving either 3 or 1.5 hours mCIMT
      supervised by a therapist. 

PMID- 26294943
TI  - Omega-3 Fatty Acid Ethyl Esters do not Improve Clopidogrel Associated P2Y12
      Inhibition in Stroke Patients.
AB  - The specific action of omega-3 fatty acid ethyl esters (OFA) in preventing
      cerebrovascular disease remains unknown, but research has demonstrated multiple
      possible mechanisms. In addition to altering lipid profiles, OFA may inhibit
      platelet aggregation. Clopidogrel inhibits platelets via the P2Y12 receptor. OFA
      may alter clopidogrel-associated platelet-inhibition via a possible combined
      effect on P2Y12 inhibition. To determine if OFA affects clopidogrel associated
      P2Y12 platelet receptor inhibition by comparing the percentage of responders in
      patients with cerebrovascular disease who were taking clopidogrel with or without
      OFA. We retrospectively reviewed data from adult patients with cerebrovascular
      disease or cerebral aneurysms and taking clopidogrel, who were seen at a single
      hospital between March 2010 to September 2011. We included 438 subjects in the
      study. For the 67 subjects who received loading doses of both clopidogrel and
      OFA, 71.6% had a P2Y12 inhibition response more than 20%, which is considered a
      positive response. For the 55 subjects who received just clopidogrel load, 67.2%
      of subjects were responders. There were 70.4% responders in the 274 subjects who
      were taking 75 mg of clopidogrel alone at home, and 73.8% responders in the 42
      subjects who were taking both clopidogrel and OFA at home. However, these
      percentage differences were not statistically significant. This study did not
      find additional P2Y12 platelet inhibition when patients were given OFA, either
      given as a loading dose or taking it daily. 

PMID- 26294944
TI  - A Real Life Clinical Practice of Neurologists in the Ambulatory Setting in
      Thailand: A Pragmatic Study.
AB  - The burden of neurological disorders is high in developing countries. Real life
      data from neurologists as to how they practice in Thailand are limited in
      literature. Practices of neurologists in a university hospital clinical setting
      in Thailand were studied. A prospective study was performed at the ambulatory
      neurology clinic, Khon Kaen University Hospital, between 1 February and 31
      October 2009. The following data were recorded: numbers of patients,
      characteristics of patients, consultation notes, and time spent for each patient.
      There were three neurologists, each of whom ran one afternoon clinic, once a
      week. There were 6137 visits during the 9 months, with an average of 681 visits
      per month. The total number of patients was 2834. The three most common diseases
      were cerebrovascular diseases (33%), epilepsy (16%), and movement disorders (non
      Parkinson's disease, 12%). Neurologists spent an average of 6.34 minutes per
      patient. In conclusion, neurologists in medical schools have limited time to take
      care of each patient. Several strategies are needed in medical education and
      neurology training to improve the quality of care. 

PMID- 26294945
TI  - Posterior Reversible Encephalopathy Syndrome and Acute Post-Streptococcal
      Glomerulonephritis Mimicking Breakthrough Seizures.
AB  - We report the case of a 14-year-old boy with a past history of primary
      generalized seizures, who had been seizure-free for 2 years on sodium valproate
      and presented with generalized tonic clonic seizures suggestive of breakthrough
      seizures. Examination revealed hypertension, impetiginous lesions of the lower
      limbs, microscopic hematuria, elevated anti-streptolysin O titre and low
      complement levels consistent with acute post-streptococcal glomerulonephritis.
      Cranial magnetic resonance imaging (MRI) demonstrated changes consistent with
      posterior reversible encephalopathy syndrome. Hypertension was controlled with
      intravenous nitroglycerin followed by oral captopril and amlodipine. Brain MRI
      changes returned normal within 2 weeks. The nephritis went in to remission within
      2 months and after 8 months the patient has been seizure free again. Posterior
      reversible encephalopathy syndrome appeared to have neither short nor
      intermediate effect on seizure control in this patient. The relationship between
      posterior reversible encephalopathy syndrome and seizures is reviewed. 

PMID- 26294946
TI  - Estimation of the Presence of Small Dense Lipoprotein Cholesterol in Acute
      Ischemic Stroke.
AB  - Small dense low-density lipoprotein (sdLDL) is an established risk factor in
      ischemic heart disease. However, its clinical significance in acute ischemic
      stroke (AIS) is uncertain. This study evaluates the prognostic value of the
      presence of sdLDL in patients with AIS by determining whether it contributes to
      clinical outcome or not. We studied 530 consecutive patients admitted within the
      first 48 hours after onset of ischemic stroke and 50 corresponding controls.
      Serum lipid parameters were measured on admission by standard laboratory methods.
      The percentage of AIS patients with sdLDL was significantly higher than the one
      of matched controls with sdLDL. Concerning comparisons between AIS patients with
      or without sdLDL, the percentages of males and patients with histories of
      smoking, hypertension, and cardiovascular disease were significantly higher in
      AIS patients with sdLDL. Concerning the grade of severity, modified Rankin Scale
      (mRS) on discharge was significantly higher in AIS patients with sdLDL. On
      logistic regression analysis, age (OR=2.29, P<0.001), male gender (OR=0.49,
      P<0.01), history of atrial fibrillation (OR=3.46, P<0.001), and the presence of
      sdLDL (OR=1.59, P<0.05) were significantly associated with poor prognosis (mRS on
      discharge >3). Our study showed that the presence of sdLDL might be independently
      associated with a poor prognosis after AIS. 

PMID- 26294947
TI  - Enterobacter muelleri sp. nov., isolated from the rhizosphere of Zea mays.
AB  - A beige-pigmented, oxidase-negative bacterial strain (JM-458T), isolated from a
      rhizosphere sample, was studied using a polyphasic taxonomic approach. Cells of
      the isolate were rod-shaped and stained Gram-negative. A comparison of the 16S
      rRNA gene sequence of strain JM-458T with sequences of the type strains of
      closely related species of the genus Enterobacter showed that it shared highest
      sequence similarity with Enterobacter mori (98.7 %), Enterobacter hormaechei
      (98.3 %), Enterobacter cloacae subsp. dissolvens, Enterobacter ludwigii and
      Enterobacter asburiae (all 98.2 %). 16S rRNA gene sequence similarities to all
      other Enterobacter species were below 98 %. Multilocus sequence analysis based on
      concatenated partial rpoB, gyrB, infB and atpD gene sequences showed a clear
      distinction of strain JM-458T from its closest related type strains. The fatty
      acid profile of the strain consisted of C16 : 0, C17 : 0 cyclo, iso-C15 : 0 2
      OH/C16 : 1omega7c and C18 : 1omega7c as major components. DNA-DNA hybridizations
      between strain JM-458T and the type strains of E. mori, E. hormaechei and E.
      ludwigii resulted in relatedness values of 29 % (reciprocal 25 %), 24 %
      (reciprocal 43 %) and 16 % (reciprocal 17 %), respectively. DNA-DNA hybridization
      results together with multilocus sequence analysis results and differential
      biochemical and chemotaxonomic properties showed that strain JM-458T represents a
      novel species of the genus Enterobacter, for which the name Enterobacter muelleri
      sp. nov. is proposed. The type strain is JM-458T ( = DSM 29346T = CIP 110826T =
      LMG 28480T = CCM 8546T).

PMID- 26294948
TI  - Disseminated Cryptococcosis Presenting as Cutaneous Cellulitis in an Adolescent
      With Systemic Lupus Erythematosus.
AB  - We report here the case of a 17-year-old girl from Pelotas, Brazil, with systemic
      lupus erythematosus and disseminated cryptococcal infection. Prior to diagnosis,
      she was a chronic user of corticosteroids and other immunosuppressive drugs. Her
      first symptoms were skin lesions that simulated bacterial cellulitis. Upon
      suspicion, we performed a biopsy and fungal infection was confirmed. Appropriate
      therapy was established, and the patient was discharged after 42 days of
      treatment in complete remission. 

PMID- 26294949
TI  - Necrotizing Fasciitis of the Abdominal Wall Caused by Serratia Marcescens.
AB  - In this article, we present the first case of necrotizing fasciitis affecting the
      abdominal wall caused by Serratia marcescens and share results of a focused
      review of S. marcescens induced necrotizing fasciitis. Our patient underwent
      aorto-femoral bypass grafting for advanced peripheral vascular disease and
      presented 3 weeks postoperatively with pain, erythema and discharge from the
      incision site in the left lower abdominal wall and underwent multiple debridement
      of the affected area. Pathology of debrided tissue indicated extensive necrosis
      involving the adipose tissue, fascia and skeletal muscle. Wound cultures were
      positive for Serratia marcescens. She was successfully treated with antibiotics
      and multiple surgical debridements. Since necrotizing fasciitis is a medical and
      surgical emergency, it is critical to examine infectivity trends, clinical
      characteristics in its causative spectrum. Using PubMed we found 17 published
      cases of necrotizing fasciitis caused by Serratia marcescens, and then analyzed
      patterns among those cases. Serratia marcescens is prominent in the community and
      hospital settings, and information on infection presentations, risk factors,
      characteristics, treatment, course, and complications as provided through this
      study can help identify cases earlier and mitigate poor outcomes. Patients with
      positive blood cultures and those patients where surgical intervention was not
      provided or delayed had a higher mortality. Surgical intervention is a definite
      way to establish the diagnosis of necrotizing infection and differentiate it from
      other entities. 

PMID- 26294950
TI  - Leptotrichia Buccalis: A Novel Cause of Chorioamnionitis.
AB  - Intra-amniotic Leptotrichia buccalis has not been previously associated with
      adverse pregnancy outcome. We report a case of chorioamnionitis and pregnancy
      loss associated with this primarily oral commensal. We review Leptotrichia
      buccalis and other oral commensals that have been identified in cases of
      intraamniotic infection. 

PMID- 26294951
TI  - Rapid Progressive Seeding of a Community Acquired Pathogen in an Immune-Competent
      Host: End Organ Damage from Head to Bone.
AB  - Methicillin-sensitive Staphylococcus aureus (MSSA) meningitis is a rare disease
      when not related to neurosurgery: there are only few reported cases in the
      literature to date. We describe a case that highlights not only meningeal but
      also diffuse and rapidly progressive systemic involvement with multi-organ
      failure. A 64-year-old male presented to our hospital with a chief complaint of
      acute worsening of his usual chronic lower back pain, progressive weakness in
      lower extremities and subjective fevers at home. Hospital course demonstrated
      MSSA bacteremia, of questionable source, that resulted in endocarditis affecting
      right and left heart in a patient with no history of intravenous drug use. The
      case was complicated by septic emboli to systemic circulation involving the
      kidneys, vertebral spine, lungs and brain with consequent meningitis and stroke,
      even when treated empirically with vancomycin and then switched to nafcillin as
      indicated. Even though MSSA infections are well known, there are very few case
      reports describing such an acute-simultaneous-manifestation of multi-end-organ
      failure, including meningitis and stroke. Our case, also presented with an
      uncommon manifestation of persistent infection dissemination despite adequate
      antibiotic treatment. 

PMID- 26294952
TI  - Lemierre Syndrome Presenting as Acute Mastoiditis in a 2-Year-Old Girl with
      Congenital Dwarfism.
AB  - Lemierre syndrome is defined by septic thrombophlebitis of the internal jugular
      vein caused by Fusobacterium. Historically, these infections originate from the
      oropharynx and typically are seen in older children, adolescents and young
      adults. More recently, otogenic sources in younger children have been described
      with increasing frequency. We present a case of a two-year old, who initially
      developed an otitis media with perforation of the tympanic membrane and went on
      to develop mastoiditis and non-occlusive thrombosis of the venous sinus and right
      internal jugular vein. Fusobacterium necrophorum was grown from operative
      cultures of the mastoid, ensuing computed tomography scan revealed occlusion of
      the internal jugular vein and the patient was successfully treated with
      clindamycin, ciprofloxacin and enoxaparin. This case demonstrates the importance
      of considering Fusobacterium in otogenic infections and the consideration of
      Lemierre syndrome when F. necrophorum is identified. 

PMID- 26294953
TI  - Pasteurella Multocida Peritonitis After Cat Scratch in a Patient with Cirrhotic
      Ascites.
AB  - Pasteurella multocida, a zoonotic agent transmitted by canines and felines, has
      been very rarely reported to cause bacterial peritonitis in humans. Pasteurella
      multocida peritonitis is associated with high mortality even with appropriate
      treatment, therefore its early recognition is essential. We report a case of
      Pasteurella multocida peritonitis following cat scratch in a patient with Child
      Pugh Class C alcoholic cirrhosis, culminating in multiple organ failure and
      death. 

PMID- 26294954
TI  - The Chronology of the International Response to Ebola in Western Africa: Lights
      and Shadows in a Frame of Conflicting Position and Figures.

PMID- 26294955
TI  - Identification of sex-associated network patterns in Vaccine-Adverse Event
      Association Network in VAERS.
AB  - BACKGROUND: Vaccines are one of the most important public health successes in
      last century. Besides effectiveness in reducing the morbidity and mortality from
      many infectious diseases, a successful vaccine program also requires a rigorous
      assessment on their safety. Due to the limitations of adverse event (AE) data
      from clinical trials and post-approval surveillance systems, novel computational
      approaches are needed to organize, visualize, and analyze such high-dimensional
      complex data. RESULTS: In this paper, we proposed a network-based approach to
      investigate the vaccine-AE association network from the Vaccine AE Reporting
      System (VAERS) data. Statistical summary was calculated using the VAERS raw data
      and represented in the Resource Description Framework (RDF). The RDF graph was
      leveraged for network analysis. Specifically, we compared network properties of
      (1) vaccine - adverse event association network based on reports collected over a
      23 year period as well as each year; and (2) sex-specific vaccine-adverse event
      association network. We observed that (1) network diameter and average path
      length don't change dramatically over a 23-year period, while the average node
      degree of these networks changes due to the different number of reports during
      different periods of time; (2) vaccine - adverse event associations derived from
      different sexes show sex-associated patterns in sex-specific vaccine-AE
      association networks. CONCLUSIONS: We have developed a network-based approach to
      investigate the vaccine-AE association network from the VAERS data. To our
      knowledge, this is the first time that a network-based approach was used to
      identify sex-specific association patterns in a spontaneous reporting system
      database. Due to unique limitations of such passive surveillance systems, our
      proposed network-based approaches have the potential to summarize and analyze the
      associations in passive surveillance systems by (1) identifying nodes of
      importance, irrespective of whether they are disproportionally reported; (2)
      providing guidance on sex-specific recommendations in personalized vaccinology.

PMID- 26294956
TI  - People Create Health: Effective Health Promotion is a Creative Process.
AB  - Effective health promotion involves the creative cultivation of physical, mental,
      social, and spiritual well-being. Efforts at health promotion produce weak and
      inconsistent benefits when it does not engage people to express their own goals
      and values. Likewise, health promotion has been ineffective when it relies only
      on instruction about facts regarding a healthy lifestyle, or focuses on reduction
      of disease rather than the cultivation of well-being. Meta-analysis of
      longitudinal studies and experimental interventions shows that improvements in
      subjective well-being lead to short-term and long-term reductions in medical
      morbidity and mortality, as well as to healthier functioning and longevity.
      However, these effects are inconsistent and weak (correlations of about 0.15).
      The most consistent and strong predictor of both subjective well-being and
      objective health status in longitudinal studies is a creative personality profile
      characterized by being highly self-directed, cooperative, and self-transcendent.
      There is a synergy among these personality traits that enhances all aspects of
      the health and happiness of people. Experimental interventions to cultivate this
      natural creative potential of people are now just beginning, but available
      exploratory research has shown that creativity can be enhanced and the changes
      are associated with widespread and profound benefits, including greater physical,
      mental, social, and spiritual well-being. In addition to benefits mediated by
      choice of diet, physical activity, and health care utilization, the effect of a
      creative personality on health may be partly mediated by effects on the
      regulation of heart rate variability. Creativity promotes autonomic balance with
      parasympathetic dominance leading to a calm alert state that promotes an
      awakening of plasticities and intelligences that stress inhibits. We suggest that
      health, happiness, and meaning can be cultivated by a complex adaptive process
      that enhances healthy functioning, plasticity and self-transcendent values.
      Health promotion is likely to have only weak and consistent benefits unless it is
      person-centered and thereby helps people to learn to live more creatively.

PMID- 26294958
TI  - Antimicrobial Peptide-Conjugated Graphene Oxide Membrane for Efficient Removal
      and Effective Killing of Multiple Drug Resistant Bacteria.
AB  - According to the World Health Organization (WHO), multiple drug-resistant (MDR)
      bacterial infection is a top threat to human health. Since bacteria evolve to
      resist antibiotics faster than scientists can develop new classes of drugs, the
      development of new materials which can be used, not only for separation, but also
      for effective disinfection of drug resistant pathogens is urgent. Driven by this
      need, we report for the first time the development of a nisin antimicrobial
      peptide conjugated, three dimensional (3D) porous graphene oxide membrane for
      identification, effective separation, and complete disinfection of MDR
      methicillin-resistant Staphylococcus aureus (MRSA) pathogens from water.
      Experimental data show that due to the size differences, MRSA is captured by the
      porous membrane, allowing only water to pass through. SEM, TEM, and fluorescence
      images confirm that pathogens are captured by the membrane. RT-PCR data with
      colony counting indicate that almost 100% of MRSA can be removed and destroyed
      from the water sample using the developed membrane. Comparison of MDR killing
      data between nisin alone, the graphene oxide membrane and the nisin attached
      graphene oxide membrane demonstrate that the nisin antimicrobial peptide attached
      graphene oxide membrane can dramatically enhance the possibility of destroying
      MRSA via a synergestic effect due to the multimodal mechanism.

PMID- 26294957
TI  - Transplantation of induced pluripotent stem cell-derived renal stem cells
      improved acute kidney injury.
AB  - BACKGROUND: Acute kidney injury (AKI) is a severe disease with high morbidity and
      mortality. Methods that promote repair of the injured kidney have been
      extensively investigated. Cell-based therapy with mesenchymal stem cells or renal
      progenitor cells (RPCs) resident in the kidney has appeared to be an effective
      strategy for the treatment of AKI. Embryonic stem cells or induced pluripotent
      stem cells (iPSCs) are also utilized for AKI recovery. However, the therapeutic
      effect of iPSC-derived RPCs for AKI has yet to be determined. METHODS: In this
      study, we induced iPSCs differentiation into RPCs using a nephrogenic cocktail of
      factors combined with the renal epithelial cell growth medium. We then
      established the rat ischemia-reperfusion injury (IR) model and transplanted the
      iPSC-derived RPCs into the injured rats in combination with the hydrogel. Next,
      we examined the renal function-related markers and renal histology to assess the
      therapeutic effect of the injected cells. Moreover, we investigated the mechanism
      by which iPSC-derived RPCs affect AKI caused by IR. RESULTS: We showed that the
      differentiation efficiency of iPSCs to RPCs increased when cultured with renal
      epithelial cell growth medium after stimulation with a nephrogenic cocktail of
      factors. The transplantation of iPSC-derived RPCs decreased the levels of
      biomarkers indicative of renal injury and attenuated the necrosis and apoptosis
      of renal tissues, but resulted in the up-regulation of renal tubules formation,
      cell proliferation, and the expression of pro-renal factors. CONCLUSION: Our
      results revealed that iPSC-derived RPCs can protect AKI rat from renal function
      impairment and severe tubular injury by up-regulating the renal tubules
      formation, promoting cell proliferation, reducing apoptosis, and regulating the
      microenvironment in the injured kidney.

PMID- 26294959
TI  - Real-time PCR quantification of infectious   laryngotracheitis virus in chicken
      tissues,   faeces, isolator-dust and bedding material over  28 days following
      infection reveals high levels   in faeces and dust.
AB  - Infectious laryngotracheitis (ILT) is an important disease of chickens caused by
      ILT virus (ILTV). We used the Australian SA2 and A20 vaccine strains of ILTV to
      determine tissue distribution and excretion characteristics of ILTV in specific
      pathogen-free chickens and to determine whether ILTV is readily detectable in
      environmental samples such as faeces, bedding material and dust using real-time
      quantitative PCR. Three groups of 10 freshly hatched chicks were placed in
      isolators and infected orally with high doses of the two strains of vaccine virus
      or left unchallenged as controls. Over a 28-day post-infection (p.i.) period,
      faecal and serum samples were collected at frequent intervals from six
      individually identified chickens in each group. Dust and litter samples from the
      isolators were collected less frequently. Tissue samples were collected from
      three to four sacrificed or dead/euthanized birds at 6, 14 and 28 days p.i.
      Infection resulted in clinical ILT, a pronounced antibody response and sustained
      qPCR detection of the viral genome in the trachea, Harderian gland, lung and
      kidney up to 28 days p.i. A high level of the viral genome was also detected in
      faeces between 2 and 7 days p.i., declining by about approximately four orders of
      magnitude to low, but detectable, levels at 21 and 28 days p.i. The finding of
      high-level shedding of ILTV in faeces warrants further investigation into the
      epidemiological role of this, and the sustained high levels of ILTV observed in
      dust suggest that it may be a useful sample material for monitoring ILTV status
      in flocks.

PMID- 26294960
TI  - Click Grafting of Alkyne-containing Vinyl Polymers onto Biosynthesized
      Extracellular Matrix Protein Containing Azide Functionality and Adhesion Control
      of Human Umbilical Vein Endothelial Cells.
AB  - In vivo incorporation of a phenylalanine (Phe) analogue, p-azidophenylalanine (p
      N3Phe) into an artificial extracellular matrix protein (aECM-CS5-ELF) was
      accomplished using a bacterial expression host that harbors the mutant
      phenylalanyl-tRNA synthetase (PheRS) with an enlarged binding pocket, in which
      the Ala294Gly/Thr251Gly mutant PheRS (PheRS**) was expressed under the control of
      T7 promoters. In this study, biosynthesized aECM-CS5-ELF containing p-N3Phe (aECM
      CS5-ELF-N3) was coupled with alkyne-containing vinyl polymers prepared via
      controlled radical polymerization of three vinyl monomers, (styrene, acrylamide,
      and N-isopropylacrylamide) using a trithiocarbonate as the RAFT agent. Grafting
      of the vinyl polymers onto the aECM was accomplished via a copper-catalyzed
      alkyne-azide click reaction. The lower critical transition temperature (LCST) was
      evaluated, as well as the solubility in aqueous and organic media, which are
      dependent on the incorporation ratio of p-N3Phe and species of graft chains, in
      which the LCST behavior was altered remarkably when poly(N-isopropylacrylamide)
      moieties were attached as side chains. Circular dichroism measurements indicate
      conformational change was not induced by the grafting. Specific adhesion of human
      umbilical vein endothelial cells (HUVECs) onto the aECM-CS5-ELF-N3-graft-poly(N
      isopropylacrylamide) composite surface and subsequent temperature-sensitive
      detachment were also demonstrated.

PMID- 26294961
TI  - Stereotactic radiosurgery XX: ocular neuromyotonia in association with gamma
      knife radiosurgery.
AB  - We report three patients who developed symptoms and signs of ocular neuromyotonia
      (ONM) 3-6 months after receiving gamma knife radiosurgery (GKS) for functioning
      pituitary tumours. All three patients were complex, requiring multi-modality
      therapy and all had received prior external irradiation to the sellar region.
      Although direct causality cannot be attributed, the timing of the development of
      the symptoms would suggest that the GKS played a contributory role in the
      development of this rare problem, which we suggest clinicians should be aware of
      as a potential complication. LEARNING POINTS: GKS can cause ONM, presenting as
      intermittent diplopia.ONM can occur quite rapidly after treatment with
      GKS.Treatment with carbamazepine is effective and improve patient's quality of
      life.

PMID- 26294962
TI  - Training for teamwork through in situ simulations.
AB  - In situ simulations allow healthcare teams to practice teamwork and communication
      as well as clinical management skills in a team's usual work setting with
      typically available resources and equipment. The purpose of this video is to
      demonstrate how to plan and conduct in situ simulation training sessions, with
      particular emphasis on how such training can be used to improve communication and
      teamwork. The video features an in situ simulation conducted at a labour and
      delivery unit in response to postpartum hemorrhage.

PMID- 26294963
TI  - Ranibizumab for Visual Impairment due to Diabetic Macular Edema: Real-World
      Evidence in the Italian Population (PRIDE Study).
AB  - Purpose. An expanded access program (PRIDE study) in Italy to provide ranibizumab
      0.5 mg to diabetic macular edema (DME) patients, prior to reimbursement. Methods.
      Open-label, prospective, phase IIIb study. Majority of patients were not
      treatment-naive before enrollment. Patients received ranibizumab as per the EU
      label (2011). Safety was assessed by incidences of ocular/systemic adverse events
      (AEs) and serious AEs (SAEs) and efficacy in terms of visual acuity (VA) change
      from baseline (decimal score or Snellen (20/value)). Results. Overall, 515
      patients (83.5%) completed the study. In unilateral/bilateral patients, commonly
      observed AEs were cardiac disorders (1.3%/1.3%) and nervous system disorders
      (1.3%/1.1%); SAEs were reported in 4.5%/4.8% of patients. Acute renal failure,
      lung carcinoma, and cardiac arrest were the causes of death in one unilateral and
      two bilateral patients. Ranibizumab improved/maintained VA (Snellen
      (20/value)/decimal scores) in both unilateral (up to -16.7/1.5) and bilateral
      patients (up to -23.6/1.2) at Month 5, with a mean of 4.15 and 4.40 injections,
      respectively. Overall, no difference was observed in the VA outcomes and
      treatment exposure between unilateral/bilateral patients. Conclusions. The PRIDE
      study provided early ranibizumab access to >600 Italian patients. Ranibizumab was
      well-tolerated and improved/maintained VA in 40.2%-68.8% patients, with no
      differences in case of unilateral or bilateral pathology. The study is registered
      with EudraCT. 

PMID- 26294964
TI  - Scleral Fixation of Posteriorly Dislocated Intraocular Lenses by 23-Gauge
      Vitrectomy without Anterior Segment Approach.
AB  - Background. To evaluate visual outcomes, corneal changes, intraocular lens (IOL)
      stability, and complications after repositioning posteriorly dislocated IOLs and
      sulcus fixation with polyester sutures. Design. Prospective consecutive case
      series. Setting. Institut Universitari Barraquer. Participants. 25 eyes of 25
      patients with posteriorly dislocated IOL. Methods. The patients underwent 23
      gauge vitrectomy via the sulcus to rescue dislocated IOLs and fix them to the
      scleral wall with a previously looped nonabsorbable polyester suture. Main
      Outcome Measures. Best corrected visual acuity (BCVA) LogMAR, corneal
      astigmatism, endothelial cell count, IOL stability, and postoperative
      complications. Results. Mean follow-up time was 18.8 +/- 10.9 months. Mean
      surgery time was 33 +/- 2 minutes. Mean BCVA improved from 0.30 +/- 0.48 before
      surgery to 0.18 +/- 0.60 (p = 0.015) at 1 month, which persisted to 12 months
      (0.18 +/- 0.60). Neither corneal astigmatism nor endothelial cell count showed
      alterations 1 year after surgery. Complications included IOL subluxation in 1 eye
      (4%), vitreous hemorrhage in 2 eyes (8%), transient hypotony in 2 eyes (8%), and
      cystic macular edema in 1 eye (4%). No patients presented retinal detachment.
      Conclusion. This surgical technique proved successful in the management of
      dislocated IOL. Functional results were good and the complications were easily
      resolved. 

PMID- 26294965
TI  - Consensus on Severity for Ocular Emergency: The BAsic SEverity Score for Common
      OculaR Emergencies [BaSe SCOrE].
AB  - Purpose. To weigh ocular emergency events according to their severity. Methods. A
      group of ophthalmologists and researchers rated the severity of 86 common ocular
      emergencies using a Delphi consensus method. The ratings were attributed on a 7
      point scale throughout a first-round survey. Then, the experts were provided with
      the median and quartiles of the ratings of each item to reevaluate the severity
      levels being aware of the group's first-round responses. The final severity
      rating for each item corresponded to the median rating provided by the last
      Delphi round. Results. We invited 398 experts, and 80 (20%) of them, from 18
      different countries, agreed to participate. A consensus was reached in the second
      round, completed by 24 experts (43%). The severity ranged from subconjunctival
      hemorrhages (median = 1, Q1 = 0; Q3 = 1) to penetrating eye injuries collapsing
      the eyeball with intraocular foreign body or panophthalmitis with infection
      following surgery (median = 5, Q1 = 5; Q3 = 6). The ratings did not differ
      according to the practice of the experts. Conclusion. These ratings could be used
      to assess the severity of ocular emergency events, to serve in composite
      algorithms for emergency triage and standardizing research in ocular emergencies.

PMID- 26294966
TI  - A Comparison of Casual In-Clinic Blood Pressure Measurements to Standardized
      Guideline-Concordant Measurements in Severely Obese Individuals.
AB  - Background/Objectives. The objective of this study was to compare casual BP taken
      in a bariatric clinic to standardized guideline-concordant BP. Subjects/Methods.
      A cross sectional analysis was performed using baseline data from a weight
      management trial. Patients were recruited from a Canadian bariatric care program.
      Standardized BP was performed using a Watch BP oscillometric device. Casual in
      clinic BP single readings, taken using a Welch Allyn oscillometric device, were
      chart-abstracted. Paired t-tests, Bland-Altman plots, and Pearson's correlations
      were used for analysis. Results. Data from 134 patients were analyzed. Mean age
      was 41.5 +/- 8.9 y, mean BMI was 46.8 +/- 6.5 kg/m(2), and 40 (30%) had prior
      hypertension. Mean casual in-clinic BP was 128.8 +/- 14.1/81.6 +/- 9.9 mmHg and
      mean standardized BP was 133.2 +/- 15.0/82.0 +/- 10.3 mmHg (difference of -4.3 +/
      12.0 for systolic (p < 0.0001) and -0.4 +/- 10.0 mmHg for diastolic BP (p =
      0.6)). Pearson's coefficients were 0.66 (p < 0.0001) for SBP and 0.50 (p <
      0.0001) for DBP. 28.4% of casual versus 26.9% of standardized measurements were
      >=140/90 mmHg (p < 0.0001). Conclusion. In this bariatric clinic, casual BP was
      unexpectedly lower than standardized BP. This could potentially lead to the
      underdiagnosis of hypertension. 

PMID- 26294967
TI  - Nutrition before and during Surgery and the Inflammatory Response of the Heart: A
      Randomized Controlled Trial.
AB  - Major surgery induces a long fasting time and provokes an inflammatory response
      which increases the risk of infections. Nutrition given before and during surgery
      can avoid fasting and has been shown to increase the arginine/asymmetric
      dimetlhylarginine ratio, a marker of nitric oxide availability, in cardiac tissue
      and increased concentrations of branched chain amino acids in blood plasma.
      However, the effect of this new nutritional strategy on organ inflammatory
      response is unknown. Therefore, we studied the effect of nutrition before and
      during cardiac surgery on myocardial inflammatory response. In this trial, 32
      patients were randomised between enteral, parenteral, and no nutrition
      supplementation (control) from 2 days before, during, up to 2 days after coronary
      artery bypass grafting. Both solutions included proteins or amino acids, glucose,
      vitamins, and minerals. Myocardial atrial tissue was sampled before and after
      revascularization and was analysed immunohistochemically, subdivided into
      cardiomyocytic, fatty, and fibrotic areas. Inflammatory cells, especially
      leukocytes, were present in cardiac tissue in all study groups. No significant
      differences were found in the myocardial inflammatory response between the
      enteral, parenteral, and control groups. In conclusion, nutrition given before
      and during surgery neither stimulates nor diminishes the myocardial inflammatory
      response in patients undergoing coronary artery bypass grafting. The trial was
      registered in Netherlands Trial Register (NTR): NTR2183. 

PMID- 26294968
TI  - The Use of Sodium Bicarbonate in the Treatment of Acidosis in Sepsis: A
      Literature Update on a Long Term Debate.
AB  - Introduction. Sepsis and its consequences such as metabolic acidosis are
      resulting in increased mortality. Although correction of metabolic acidosis with
      sodium bicarbonate seems a reasonable approach, there is ongoing debate regarding
      the role of bicarbonates as a therapeutic option. Methods. We conducted a PubMed
      literature search in order to identify published literature related to the
      effects of sodium bicarbonate treatment on metabolic acidosis due to sepsis. The
      search included all articles published in English in the last 35 years. Results.
      There is ongoing debate regarding the use of bicarbonates for the treatment of
      acidosis in sepsis, but there is a trend towards not using bicarbonate in sepsis
      patients with arterial blood gas pH > 7.15. Conclusions. Routine use of
      bicarbonate for treatment of severe acidemia and lactic acidosis due to sepsis is
      subject of controversy, and current opinion does not favor routine use of
      bicarbonates. However, available evidence is inconclusive, and more studies are
      required to determine the potential benefit, if any, of bicarbonate therapy in
      the sepsis patient with acidosis. 

PMID- 26294969
TI  - Tactile Electrosurgical Ablation: A Technique for the Treatment of Intractable
      Heavy and Prolonged Menstrual Bleeding.
AB  - Objective. To study the efficacy and safety of tactile electrosurgical ablation
      (TEA) in stopping a persistent attack of abnormal uterine bleeding not responding
      to medical and hormonal therapy. Methods. This is a case series of 19 cases with
      intractable abnormal uterine bleeding, who underwent TEA at the Women's Health
      Center of Assiut University. The outcomes measured were; patient's acceptability,
      operative time, complications, menstrual outcomes, and reintervention. Results.
      None of the 19 counseled cases refused the TEA procedure which took 6-10 minutes
      without intraoperative complications. The procedure was successful in the
      immediate cessation of bleeding in 18 out of 19 cases. During the 24-month follow
      up period, 9 cases developed amenorrhea, 5 had scanty menstrual bleeding, 3 were
      regularly menstruating, 1 case underwent repeat TEA ablation, and one underwent a
      hysterectomy. Conclusions. TEA represents a safe, inexpensive, and successful
      method for management of uterine bleeding emergencies with additional long-term
      beneficial effects. However, more studies with more cases and longer follow-up
      periods are warranted. 

PMID- 26294970
TI  - The Role of VATS in Lung Cancer Surgery: Current Status and Prospects for
      Development.
AB  - Since the introduction of anatomic lung resection by video-assisted thoracoscopic
      surgery (VATS) 20 years ago, VATS has experienced major advances in both
      equipment and technique, introducing a technical challenge in the surgical
      treatment of both benign and malignant lung disease. The demonstrated safety,
      decreased morbidity, and equivalent efficacy of this minimally invasive technique
      have led to the acceptance of VATS as a standard surgical modality for early
      stage lung cancer and increasing application to more advanced disease. Formerly
      there was much debate about the feasibility of the technique in cancer surgery
      and proper lymph node handling. Although there is a lack of proper randomized
      studies, it is now generally accepted that the outcome of a VATS procedure is at
      least not inferior to a resection via a traditional thoracotomy. 

PMID- 26294971
TI  - Is the Pulmonary Embolism Severity Index Being Routinely Used in Clinical
      Practice?
AB  - Background. The Pulmonary Embolism Severity Index (PESI) score can risk-stratify
      patients with PE but its widespread use is uncertain. With the PESI, we compared
      length of hospital stay between low, moderate, and high risk PE patients and
      determined the number of low risk PE patients who were discharged early. Methods.
      PE patients admitted to St. Joseph Mercy Oakland Hospital from January 2005 to
      August 2010 were screened. PESI score stratified acute PE patients into low
      (<85), moderate (86-105), and high (>105) risk categories and their length of
      hospital stay was compared. Patients with low risk PE discharged early (<=3 days)
      were calculated. Results. Among 315 PE patients, 51.7% were at low risk. No
      significant difference in hospital stay between low (7.11 +/- 3 d) and moderate
      (6.88 +/- 2.9 d) risk, p > 0.05, as well as low and high risk (7.28 +/- 3.0 d), p
      > 0.05, was found. 9% of low risk patients were discharged <= 3 days.
      Conclusions. There was no significant difference in length of hospital stay
      between low and high risk groups and only a small number of low risk patients
      were discharged from the hospital early suggesting that risk tools like PESI may
      not have a widespread use. 

PMID- 26294972
TI  - Screening Optimization of Latent Tuberculosis Infection in Rheumatoid Arthritis
      Patients.
AB  - Objective. Rheumatoid arthritis (RA) patients are at increased risk of latent
      tuberculosis infection (LTBI) but there are no clear guidelines for LTBI
      screening with Tuberculin Skin Test (TST) or Quantiferon TB Gold testing (QFT-G).
      Methods. A retrospective study was conducted in a high risk, largely foreign
      born, inner city, RA population. After screening 280 RA patients, 134 patients
      who had both TST and QFT-G testing performed during their initial evaluation were
      included. Results. Out of 132 RA patients included in our analysis, 50 (37.8%)
      patients were diagnosed with LTBI with either positive TST 42 (31.8%) or QFT-G 23
      (17.4%). 15 (11.4%) were positive and 82 (62.1%) were negative for both tests.
      The agreement between TST and QFT-G was 73.5% (Kappa 0.305, CI = 95% 0.147-0.463,
      p = 0.081).  Conclusions. There was low-moderate agreement (kappa = 0.305)
      between TST and QFT-G. In the absence of clearly defined gold standard and
      limitations associated with both tests, we propose early screening with both
      tests for patients who need prompt treatment with BRMs. Patients who are not
      immediate candidates for BRM treatment may be safely and cost effectively
      screened with a two-step process: initial screening with TST and if negative,
      IGRA testing. Patients positive for either test should be promptly treated. 

PMID- 26294973
TI  - Hyperuricemia: An Early Marker for Severity of Illness in Sepsis.
AB  - Background. Uric acid can acutely activate various inflammatory transcription
      factors. Since high levels of oxyradicals and lower antioxidant levels in septic
      patients are believed to result in multiorgan failure, uric acid levels could be
      used as a marker of oxidative stress and poor prognosis in patients with sepsis.
      Design. We conducted a prospective cohort study on Medical Intensive Care Unit
      (MICU) patients and hypothesized that elevated uric acid in patients with sepsis
      is predictive of greater morbidity. The primary end point was the correlation
      between hyperuricemia and the morbidity rate. Secondary end points were Acute
      Kidney Injury (AKI), mortality, Acute Respiratory Distress Syndrome (ARDS), and
      duration of stay. Results. We enrolled 144 patients. 54 (37.5%) had the primary
      end point of hyperuricemia. The overall morbidity rate was 85.2%. The probability
      of having hyperuricemia along with AKI was 68.5% and without AKI was 31.5%.
      Meanwhile the probability of having a uric acid value <7 mg/dL along with AKI was
      18.9% and without AKI was 81.1% (p value < 0.0001). Conclusion. We report that
      elevated uric acid levels on arrival to the MICU in patients with sepsis are
      associated with poor prognosis. These patients are at an increased risk for AKI
      and ARDS. 

PMID- 26294974
TI  - High Prevalence of Cardiovascular Disease in End-Stage Kidney Disease Patients
      Ongoing Hemodialysis in Peru: Why Should We Care About It?
AB  - Purpose. To determine clinical, biochemical, and pharmacological characteristics
      as well as cardiovascular disease prevalence and its associated factors among end
      stage kidney disease patients receiving hemodialysis in the main hemodialysis
      center in Lima, Peru. Methods. This cross-sectional study included 103 patients.
      Clinical charts were reviewed and an echocardiogram was performed to determine
      prevalence of cardiovascular disease, defined as the presence of
      systolic/diastolic dysfunction, coronary heart disease, ventricular dysrhythmias,
      cerebrovascular disease, and/or peripheral vascular disease. Associations between
      cardiovascular disease and clinical, biochemical, and dialysis factors were
      sought using prevalence ratio. A robust Poisson regression model was used to
      quantify possible associations. Results. Cardiovascular disease prevalence was
      81.6%, mainly due to diastolic dysfunction. It was significantly associated with
      age older than 50 years, metabolic syndrome, C-reactive protein levels, effective
      blood flow <= 300 mL/min, severe anemia, and absence of mild anemia. However, in
      the regression analysis only age older than 50 years, effective blood flow <= 300
      mL/min, and absence of mild anemia were associated. Conclusions. Cardiovascular
      disease prevalence is high in patients receiving hemodialysis in the main center
      in Lima. Diastolic dysfunction, age, specific hemoglobin levels, and effective
      blood flow may play an important role. 

PMID- 26294975
TI  - High (>=6.5) Spontaneous and Persistent Urinary pH Is Protective of Renal
      Function at Baseline and during Disease Course in Idiopathic Membranous
      Nephropathy.
AB  - Metabolic acidosis correction in advanced renal failure slows renal function
      decline attributed to tubulointerstitial damage (TID) reduction. No study
      evaluated if spontaneous baseline high urinary pH (UpH) is renoprotective in
      patients with normal renal function and without metabolic acidosis. The study
      tested this hypothesis in idiopathic membranous nephropathy (IMN). Eighty-five
      patients (follow-up 81 +/- 54 months) measured UpH, serum creatinine, eGFR,
      protein/creatinine ratio, fractional excretion of albumin, IgG, alpha1
      microglobulin, and urinary N-acetyl-beta-D-glucosaminidase (beta-NAG)/creatinine
      ratio. Twenty-eight patients (33%) had UpH >= 6.5 and 57 (67%) pH < 6.5; high
      versus low UpH patients had significantly lower values of the tubulointerstitial
      damage (TID) markers FE alpha1m and beta-NAG and significantly better baseline
      renal function. These differences persisted over time in a subset of 38 patients
      with 5 measurements along 53 +/- 26 months. In 29 patients with nephrotic
      syndrome (NS) treated with supportive therapy (follow-up: 80 +/- 52 months) renal
      function was stable in 10 high and significantly worse in 19 low UpH patients.
      Steroids + cyclophosphamide treatment in 35 NS patients masks the renoprotection
      of high UpH. Conclusions. In IMN high and persistent UpH is associated with
      reduction of the proteinuric markers of tubulointerstitial damage and baseline
      better renal function in all patients and in NS patients treated only with
      supportive therapy during disease course. The factors associated with high pH
      dependent renoprotection were lower values of TID markers, eGFR >= 60 mL/min, BP
      < 140/90 mmHg, and age < 55 years. 

PMID- 26294976
TI  - Clinical Use of Diuretics in Heart Failure, Cirrhosis, and Nephrotic Syndrome.
AB  - Diuretics play significant role in pharmacology and treatment options in
      medicine. This paper aims to review and evaluate the clinical use of diuretics in
      conditions that lead to fluid overload in the body such as cardiac failure,
      cirrhosis, and nephrotic syndrome. To know the principles of treatment it is
      essential to understand the underlying pathophysiological mechanisms that cause
      the need of diuresis in the human body. Various classes of diuretics exist, each
      having a unique mode of action. A systemic approach for management is recommended
      based on the current guidelines, starting from thiazides and proceeding to loop
      diuretics. The first condition for discussion in the paper is cardiac failure.
      Treatment of ascites in liver cirrhosis with spironolactone as the primary agent
      is highlighted with further therapeutic options. Lastly, management choices for
      nephrotic syndrome are discussed and recommended beginning from basic sodium
      restriction to combined diuretic therapies. Major side effects are discussed. 

PMID- 26294977
TI  - Mathematical Equations to Predict Positive Airway Pressures for Obstructive Sleep
      Apnea: A Systematic Review.
AB  - Objective. To systematically review the international literature for mathematical
      equations used to predict effective pressures for positive airway pressure (PAP)
      devices. Methods. Google Scholar, PubMed, Scopus, Embase, Web of Science, CINAHL,
      and The Cochrane Library were searched through June 27, 2015. The PRISMA
      statement was followed. There was no language limitation. Results. 709 articles
      were screened, fifty were downloaded, and twenty-six studies presented equations
      that met the inclusion and exclusion criteria. In total, there were 4,436
      patients in the development phases and 3,489 patients in the validation phases.
      Studies performed multiple linear regressions analyses as part of the equation(s)
      development and included the following variables: physical characteristics,
      polysomnography data, behavioral characteristics, and miscellaneous
      characteristics, which were all predictive to a variable extent. Of the published
      variables, body mass index (BMI) and mean oxygen saturation are the most heavily
      weighted, while BMI (eighteen studies), apnea-hypopnea index (seventeen studies),
      and neck circumference (eleven studies) were the variables most frequently used
      in the mathematical equations. Ten studies were from Asian countries and sixteen
      were from non-Asian countries. Conclusion. This systematic review identified
      twenty-six unique studies reporting mathematical equations which are summarized.
      Overall, BMI and mean oxygen saturation are the most heavily weighted. 

PMID- 26294978
TI  - Physiological Sleep Propensity Might Be Unaffected by Significant Variations in
      Self-Reported Well-Being, Activity, and Mood.
AB  - Background and Objective. Depressive state is often associated with such physical
      symptoms as general weakness, fatigue, tiredness, slowness, reduced activity, low
      energy, and sleepiness. The involvement of the sleep-wake regulating mechanisms
      has been proposed as one of the plausible explanations of this association. Both
      physical depressive symptoms and increased physiological sleep propensity can
      result from disordered and insufficient sleep. In order to avoid the influence of
      disordered and insufficient sleep, daytime and nighttime sleepiness were tested
      in winter depression characterized by normal night sleep duration and
      architecture. Materials and Methods. A total sample consisted of 6 healthy
      controls and 9 patients suffered from depression in the previous winter season.
      Sleep latency was determined across 5 daytime and 4 nighttime 20-min attempts to
      nap in summer as well as in winter before and after a week of 2-hour evening
      treatment with bright light. Results and Conclusions. Patients self-reported
      abnormally lowered well-being, activity, and mood only in winter before the
      treatment. Physiological sleep propensity was neither abnormal nor linked to
      significant changes in well-being, activity, and mood following the treatment and
      change in season. It seems unlikely that the mechanisms regulating the sleep-wake
      cycle contributed to the development of the physical depressive symptoms. 

PMID- 26294979
TI  - Long-Term Spatiotemporal Reconfiguration of Neuronal Activity Revealed by Voltage
      Sensitive Dye Imaging in the Cerebellar Granular Layer.
AB  - Understanding the spatiotemporal organization of long-term synaptic plasticity in
      neuronal networks demands techniques capable of monitoring changes in synaptic
      responsiveness over extended multineuronal structures. Among these techniques,
      voltage-sensitive dye imaging (VSD imaging) is of particular interest due to its
      good spatial resolution. However, improvements of the technique are needed in
      order to overcome limits imposed by its low signal-to-noise ratio. Here, we show
      that VSD imaging can detect long-term potentiation (LTP) and long-term depression
      (LTD) in acute cerebellar slices. Combined VSD imaging and patch-clamp recordings
      revealed that the most excited regions were predominantly associated with granule
      cells (GrCs) generating EPSP-spike complexes, while poorly responding regions
      were associated with GrCs generating EPSPs only. The correspondence with cellular
      changes occurring during LTP and LTD was highlighted by a vector representation
      obtained by combining amplitude with time-to-peak of VSD signals. This showed
      that LTP occurred in the most excited regions lying in the core of activated
      areas and increased the number of EPSP-spike complexes, while LTD occurred in the
      less excited regions lying in the surround. VSD imaging appears to be an
      efficient tool for investigating how synaptic plasticity contributes to the
      reorganization of multineuronal activity in neuronal circuits. 

PMID- 26294981
TI  - Bladder Explosion during Transurethral Resection of the Prostate with Nitrous
      Oxide Inhalation.
AB  - Bladder explosions are a rare complication of transurethral resection of the
      prostate. We report a patient who suffered a bladder rupture following
      transurethral resection of the prostate. Although explosive gases accumulate
      during the procedure, a high concentration of oxygen is needed to support an
      explosion. This rare phenomenon can be prevented by preventing the flow of room
      air into the bladder during the procedure to maintain a low concentration of
      oxygen inside the bladder. 

PMID- 26294980
TI  - Dopaminergic Modulation of Striatal Inhibitory Transmission and Long-Term
      Plasticity.
AB  - Dopamine (DA) modulates glutamatergic synaptic transmission and its plasticity in
      the striatum; however it is not well known how DA modulates long-term plasticity
      of striatal GABAergic inhibitory synapses. This work focused on the analysis of
      both dopaminergic modulation of inhibitory synapses and the synaptic plasticity
      established between GABAergic afferents to medium spiny neurons (MSNs). Our
      results showed that low and high DA concentrations mainly reduced the amplitude
      of inhibitory synaptic response; however detailed analysis of the D1 and D2
      participation in this modulation displayed a wide variability in synaptic
      response. Analyzing DA participation in striatal GABAergic plasticity we observed
      that high frequency stimulation (HFS) of GABAergic interneurons in the presence
      of DA at a low concentration (200 nM) favored the expression of inhibitory
      striatal LTD, whereas higher concentration of DA (20 MUM) primarily induced LTP.
      Interestingly, the plasticity induced in an animal model of striatal degeneration
      mimicked that induced in the presence of DA at a high concentration, which was
      not abolished with D2 antagonist but was prevented by PKA blocker.

PMID- 26294982
TI  - Early Cardiac Tamponade in a Patient with Postsurgical Hypothyroidism.
AB  - Pericardial effusion is a common cardiac manifestation of hypothyroidism, but
      effusion resulting in cardiac tamponade is extremely rare. We present a case of a
      56-year-old African American woman with slurred speech and altered mental status
      that was initially suspected to have stroke. Her chest X-ray revealed
      cardiomegaly and subsequent echocardiogram showed a large pericardial effusion
      with echocardiographic evidence of cardiac tamponade. Clinically, patient did not
      have pulsus paradoxus or hypotension. Further questioning revealed a history of
      total surgical thyroidectomy and noncompliance with thyroid replacement therapy.
      Pericardiocentesis was performed promptly and thyroxine replacement therapy was
      started. Thereafter, her mental status improved significantly. The management of
      pericardial effusion associated with hypothyroidism varies depending on size of
      effusion and hemodynamic stability of the patient. The management strategy ranges
      from conservative management with close monitoring and thyroxine replacement to
      pericardiocentesis or creation of a pericardial window. 

PMID- 26294983
TI  - A Rare Cause of Intestinal Obstruction in Infants: Ileum Duplication Cyst and
      Literature Review.
AB  - Cases of neonatal gastrointestinal system (GIS) obstruction are quite complex for
      pediatric surgery clinics. A rare cause of intestinal obstruction is the
      duplication cyst (DC). A three-day-old male patient presented at our clinic with
      a history of abdominal distension and bilious vomiting on the second day
      following birth. Although pathology had not yet been determined from observation
      and examination, surgery was performed when the patient could not tolerate oral
      feeding. An ileal DC forming an incomplete obstruction was observed. Ileoileal
      anastomosis was performed on the patient. Because DCs can present with different
      clinical symptoms, it is quite difficult to diagnose them in neonate patients.
      Lacking an imaging method that can provide an exact diagnosis, the diagnostic
      laparotomy is a suitable approach for both diagnosis and treatment to avoid
      delays in treatment. 

PMID- 26294984
TI  - Acute Portomesenteric Venous Thrombosis following Laparoscopic Small Bowel
      Resection and Ventral Hernia Repair.
AB  - Acute portomesenteric venous thrombosis is a rare but life-threatening
      complication of laparoscopic surgery that has been described in literature.
      Prompt diagnosis and early initiation of treatment are vital to prevent life
      threatening complications such as mesenteric ischemia and infarction. A 51-year
      old lady had laparoscopic small bowel resection and primary anastomosis with
      ventral hernia repair 4 weeks earlier for partial small bowel obstruction. Her
      postoperative period was uneventful and she was discharged home. Four weeks after
      surgery she developed watery diarrhea and generalized abdominal pain for four-day
      duration. A computed tomography of the abdomen revealed portomesenteric venous
      thrombosis although a computed tomography of abdomen before surgery 4 weeks back
      did not show any portomesenteric venous thrombosis. We are reporting a case of
      acute portomesenteric venous thrombosis as a complication of laparoscopic
      surgery. 

PMID- 26294985
TI  - Mild Phenotype in a Patient with a De Novo 6.3 Mb Distal Deletion at
      10q26.2q26.3.
AB  - We report on a 29-year-old Greek-Cypriot female with a de novo 6.3 Mb distal
      10q26.2q26.3 deletion. She had a very mild neurocognitive phenotype with near
      normal development and intellect. In addition, she had certain distinctive
      features and postural orthostatic tachycardia. We review the relevant literature
      and postulate that certain of her features can be diagnostically relevant. This
      report illustrates the powerful diagnostic ability of array-CGH in the
      elucidation of relatively mild phenotypes. 

PMID- 26294986
TI  - A Case of Orf Disease Complicated with Erythema Multiforme and Bullous Pemphigoid
      Like Eruptions.
AB  - Parapoxvirus infection in sheep and goats is usually referred to as contagious
      pustular dermatitis/ecthyma, or orf, and the corresponding human infection is
      referred to as orf. In humans, after a brief incubation period of 3 to 5 days,
      lesions begin as pruritic erythematous macules and then rise to form papules,
      often with a target appearance. Lesions become nodular or vesicular, and orf
      lesions often ulcerate after 14 to 21 days. Erythema multiforme and bullous
      pemphigoid have been associated with parapoxvirus infections and they are rare
      complications of orf disease. In this case report, we presented a 36-year-old
      woman with history of contact with sheep, developing a typical orf lesion that is
      complicated with erythema multiforme and bullous pemphigoid-like eruptions. 

PMID- 26294987
TI  - Pulmonary Thromboembolism Complicating Amebic Liver Abscess: First Reported Case
      in the United States-Case Report and Literature Review.
AB  - Even in the absence of Amebic colitis, Amebic liver abscess (ALA) is the most
      common extraintestinal complication of Entamoeba histolytica infection. In the
      USA, it is most prevalent in middle aged immigrant males from endemic countries
      such as Africa, Mexico, and India. One of the complications of ALA is inferior
      vena cava (IVC) thrombosis, which is believed to result from the mechanical
      compression of the IVC and the consequent thrombogenic nidus elicited from the
      resultant inflammatory response. There are very few reported cases and even fewer
      in which the thrombus became a harbinger to pulmonary thromboembolism. We present
      the case of a 43-year-old male from West Africa who presented with the chief
      complaint of right upper quadrant abdominal pain for one week associated with
      persistent nonproductive cough. He had a positive serum Entamoeba histolytica
      antibody with CT scan findings of a hepatic abscess with thrombosis of the
      hepatic vein and inferior vena cava and numerous bilateral pulmonary emboli. This
      amebic liver abscess was successfully treated with metronidazole and paromomycin,
      whereas the pulmonary thromboembolism was managed with medical anticoagulation.
      Based on current knowledge, this is the first reported case in the USA. 

PMID- 26294988
TI  - Use of Cetuximab in Combination with Cisplatin and Adjuvant Pelvic Radiation for
      Stage IIIB Vulvar Carcinoma.
AB  - Vulvar cancer is a rare carcinoma constituting only 4% of gynecologic
      malignancies and 0.6% of female cancers. Most chemotherapy regimens have been
      created from extrapolation from anal and cervical cancer research. Advanced
      stages have the worst prognosis and oftentimes invasive surgical procedures are
      needed to cure disease with high recurrence rates. Case. A 50 yo G2P2 presented
      for a 2 cm mass in her right labia. The patient underwent a partial radical
      vulvectomy and bilateral superficial and deep inguinal lymph node dissection.
      Bilateral inguinal lymph nodes were positive for residual disease. The patient
      underwent whole pelvic radiation with cisplatin as a radiosensitizer. The primary
      tumor was epidermal growth factor receptor (EGFR) positive and cetuximab, a
      monoclonal antibody to EGFR, was added. The patient underwent seven cycles of
      chemotherapy including cisplatin and cetuximab with adjuvant radiation therapy to
      the pelvis. She currently is without evidence of disease recurrence since
      completing treatment 4 years ago. Conclusion. One previous case report showed
      short-term palliative success of five months for recurrent, metastatic vulvar
      cancer. This case suggests that cetuximab could possibly be used in initial
      management of patients with advanced stages of vulvar cancer to improve
      prognosis. 

PMID- 26294989
TI  - Antenatal Diagnosis of a Rare Neural Tube Defect: Sincipital Encephalocele.
AB  - Context. Fetal sincipital encephalocele is one of the most serious congenital
      neural tube defects with a high risk of mortality and neonatal morbidity.
      Prenatal diagnosis of this malformation is important in fetal medicine. Case
      Report. We report a case of prenatal diagnosis of sincipital encephalocele using
      ultrasound and MRI imaging. The diagnosis was done at 25 weeks of gestation by
      identifying an anterior cephalic protrusion through a defect in the skull.
      Conclusion. Through this case, we discuss the differential diagnosis, management,
      and prognosis of such lesions. 

PMID- 26294990
TI  - Successful Pregnancies after the Treatment of a Thymic Carcinoid.
AB  - The present report describes the case of a woman diagnosed with an
      adrenocorticotropic hormone- (ACTH-) secreting thymic carcinoid associated with
      Cushing's syndrome. Treatment consisted of tumour resection and 131-I-meta
      iodobenzylguanidine (MIBG) therapy. In spite of her iatrogenic menopausal state
      she twice became pregnant and delivered two healthy babies but developed
      recurrences during both pregnancies. The last recurrence presented as a primary
      breast cancer. Despite poor prognosis our patient survived for eleven years. To
      our knowledge this is the first report of successful pregnancy and delivery in a
      patient with a thymic carcinoid. 

PMID- 26294991
TI  - Prenatal Diagnosis of Rare Familial Unbalanced Translocation of Chromosomes 7 and
      12.
AB  - Case Details. We report rare familial unbalanced translocation of chromosomes 7
      and 12, which was diagnosed prenatally at 20+3 weeks of gestation. Woman's
      partner had been tested in the past and was found to be a carrier of a balanced
      translocation; his karyotype showed a balanced reciprocal translocation of 46,
      XY, t(7;12)(q34;q24,32). Partner's brother had an unbalanced form of the
      translocation with severe learning disability. The diagnosis of the anomaly was
      based on two- and three-dimensional ultrasound and microarray analysis.
      Ultrasonography findings included fetal microcephaly and alobar
      holoprosencephaly, dysmorphic face (flat occiput, absent nasal bone,
      microphthalmia, hypotelorism, and single nostril), and hyperechogenic bowel.
      Genome-wide array analysis and cytogenetic results from the amniotic fluid showed
      unbalanced translocation in chromosomes 7 and 12 with deletion of an
      approximately 16.5 Mb and a duplication of 6.1 Mb, respectively, Arr
      7q34q36.3(142,668,576-159,161,648)x1,12q24.32q24.33(127,708,720-133,777,560)x3,
      karyotype (der (7) t(7;12) (q34;q24)pat). This unbalanced translocation was due
      to the segregation of the father's balanced translocation. In this particular
      case, the recurrence of an unbalanced translocation in the subsequent pregnancies
      is estimated to be 20%. Understanding the individuals' phenotype in association
      with the gain and loss of copy number is important and can further provide us
      with information on that particular region of the named chromosomes. 

PMID- 26294992
TI  - Two Cases of Pneumatosis Intestinalis during Cetuximab Therapy for Advanced Head
      and Neck Cancer.
AB  - Pneumatosis intestinalis is a rare but known potential complication of treatment
      with cetuximab. Here we present two cases of pneumatosis intestinalis occurring
      in patients who were receiving cetuximab as treatment for advanced head and neck
      cancer. In both cases, cetuximab was discontinued after discovery of the
      pneumatosis intestinalis. 

PMID- 26294993
TI  - Primary Intracranial Melanoma with Early Leptomeningeal Spread: A Case Report and
      Treatment Options Available.
AB  - Primary CNS melanomas are rare and they constitute about 1% of all cases of
      melanomas and 0.07% of all brain tumors. These tumors are aggressive in nature
      and may metastasise to other organs. Till date less than 25 cases have been
      reported in the literature. The primary treatment for local intraparenchymal
      tumours is complete resection and/or radiotherapy and it is associated with good
      survival. However once there is disease spread to leptomeninges the overall
      median survival is around 10 weeks. In this case report we describe a primary
      intracranial melanoma without any dural attachment in 16-year-old boy who had
      radical excision of the tumor followed by radiotherapy who eventually had rapidly
      developed leptomeningeal disease and review the literature with a focus on the
      clinic pathological, radiological, and treatment options. 

PMID- 26294994
TI  - Managing Drawbacks in Unconventional Successful Glaucoma Surgery: A Case Report
      of Stent Exposure.
AB  - Traditional options in managing failed trabeculectomy (bleb needling, revision,
      additional incisional surgery and tube surgery) have a relatively high failure
      and complication rate. The use of microinvasive glaucoma surgery (MIGS) has
      generally been reserved to mild to moderate glaucoma cases, proving good safety
      profiles but significant limitations in terms of efficacy. We describe a patient
      who underwent MIGS (XEN Aquesys subconjunctival shunt implantation) after a prior
      failed trabeculectomy. After the surgery, the IOP was well controlled but as the
      stent was close to an area of scarred conjunctiva of the previous trabeculectomy,
      it became partially exposed. As a complete success was achieved, we decided to
      remove the conjunctiva over the exposed area and replace it by an amniotic
      membrane transplantation and a conjunctiva autograft. Six months after surgery,
      the unmedicated IOP is still well controlled with complete visual acuity
      recovery. 

PMID- 26294995
TI  - Nonsurgical Corrective Union of Osteoporotic Vertebral Fracture with Once-Weekly
      Teriparatide.
AB  - Osteoporotic vertebral fractures usually heal with kyphotic deformities with
      subsidence of the vertebral body when treated conservatively. Corrective
      vertebral union using only antiosteoporotic pharmacotherapy without surgical
      intervention has not been reported previously. An 81-year-old female with
      osteoporosis presented with symptomatic fresh L1 vertebral fracture with
      intravertebral cleft. Segmental vertebral kyphosis angle (VKA) at L1 was 20
      degrees  at diagnosis. Once-weekly teriparatide administration, hospitalized
      rest, and application of a thoracolumbosacral orthosis alleviated symptoms within
      2 months. Corrective union of the affected vertebra was obtained with these
      treatments. VKA at 2 months after injury was 8 degrees  (correction, 12 degrees )
      and was maintained as of the latest follow-up at 7 months. Teriparatide has
      potent bone-forming effects and has thus been expected to enhance fracture
      healing. Based on the clinical experience of this case, teriparatide may have the
      potential to allow correction of unstable vertebral fractures without surgical
      intervention. 

PMID- 26294996
TI  - Metastatic Prostate Cancer to the Left Temporal Bone: A Case Report and Review of
      the Literature.
AB  - Breast, lung, and prostate cancers are the three most common malignancies to
      metastasize to the temporal bone. Still, metastatic prostate cancer of the
      temporal bone is a rare finding, with approximately 21 cases reported in the
      literature and only 2 cases discovered more than 10 years after initial treatment
      of the primary. This disease may be asymptomatic and discovered incidentally;
      however, hearing loss, otalgia, cranial nerve palsies, and visual changes can all
      be presenting symptoms. We present the case of a 95-year-old man with history of
      primary prostate cancer treated 12 years earlier that was seen for new-onset
      asymmetric hearing loss and otalgia. The tympanic membranes and middle ears were
      normal; however, based on radiologic findings and eventual biopsy, the patient
      was diagnosed with extensive metastatic prostate cancer to the left temporal
      bone. This case (1) demonstrates that a high index of suspicion for unusual
      etiologies of seemingly benign symptoms must be maintained in elderly patients
      having prior history of cancer and (2) substantiates the value of temporal bone
      imaging when diagnosis may be unclear from history and physical exam. 

PMID- 26294997
TI  - Central Hypoventilation: A Case Study of Issues Associated with Travel Medicine
      and Respiratory Infection.
AB  - Aim. We presented the case of a child with central hypoventilation syndrome (CHS)
      to highlight issues that need to be considered in planning long-haul flight and
      problems that may arise during the flight. Case. The pediatric intensive care
      unit (PICU) received a child with central hypoventilation syndrome (Ondine's
      curse) on nocturnal ventilatory support who travelled to Hong Kong on a make-a
      wish journey. He was diagnosed with central hypoventilation and had been well
      managed in Canada. During a long-haul aviation travel, he developed respiratory
      symptoms and desaturations. The child arrived in Hong Kong and his respiratory
      symptoms persisted. He was taken to a PICU for management. The child remained
      well and investigations revealed no pathogen to account for his respiratory
      infection. He went on with his make-a-wish journey. Conclusions. Various issues
      of travel medicine such as equipment, airline arrangement, in-flight ventilatory
      support, travel insurance, and respiratory infection are explored and discussed.
      This case illustrates that long-haul air travel is possible for children with
      respiratory compromise if anticipatory preparation is timely arranged. 

PMID- 26294998
TI  - A Child with Lung Hypoplasia, Congenital Heart Disease, Hemifacial Microsomia,
      and Inguinal Hernia: Ipsilateral Congenital Malformations.
AB  - A 3-year-old Chinese boy was diagnosed with ipsilateral congenital malformations:
      right lung hypoplasia, dextroversion of heart, atrial septal defect, hepatic vein
      drainage directly into the right atrium, facial asymmetry, right microtia and
      congenital deafness, and indirect inguinal hernia. He underwent indirect inguinal
      hernia repair at the age of 2. Although without any facial plastic surgery
      performed, he underwent a repair of atrial septal defect and recovered
      uneventfully. At 6-month follow-up, the patient was free from any symptom of
      dyspnea; his heart function returned to the first grade. 

PMID- 26294999
TI  - Epithelioid Myofibroblastoma in an Old-Male Breast: A Case Report with MRI
      Findings.
AB  - Myofibroblastoma of the breast (MFB) is a very rare benign stromal tumor. In
      recent years, increase in mammographic screenings has resulted in increased
      diagnosis of MFB. Most cases are old males and postmenopausal women. MFB may be
      confused as malignant, clinically, morphologically, or by imaging.
      Immunohistochemistry is essential for final diagnosis in these cases. We report a
      case of a pathologically diagnosed MFB in an 80-year-old male patient who had
      coexisting prostate cancer and describe its imaging characteristics, especially
      magnetic resonance imaging (MRI). In this paper, histopathological and MRI
      findings of the MFB were discussed. 

PMID- 26295000
TI  - Multifocal Insulinoma in Pancreas and Effect of Intraoperative Ultrasonography.
AB  - Insulinoma is the most frequently seen functional pancreatic neuroendocrine
      tumor. The incidence of multifocal insulinoma is lower than 10%. Its treatment is
      direct or laparoscopic excision. The present case was examined with the findings
      of hypoglycemia and hypercalcemia, and as there was high insulin and C-peptide
      levels the initial diagnosis was insulinoma. The case was investigated in terms
      of MEN 1. During preoperative screening for localization, there was one focus in
      the head of the pancreas in the abdominal tomography and two foci in endoscopic
      ultrasonography. No other focus was detected through intraoperative visual or
      manual palpation. However, five foci were detected during operation by
      intraoperative ultrasonography. The relation of masses with the main pancreatic
      canal was evaluated and they were excised by enucleation method. There was no
      recurrence during the postoperative 18-month follow-up of the patient. As a
      result, during treatment for insulinoma, it should be kept in mind that there
      might be multifocal foci. In all insulinomas, the whole pancreas should be
      evaluated with intraoperative ultrasonography because none of the current
      preoperative diagnostic methods are as sensitive as manual palpation of pancreas
      and intraoperative ultrasonography. The intraoperative detection of synchronous
      five foci in pancreas is quite a rare condition. 

PMID- 26295001
TI  - Bilateral Ureteral Obstruction in Children after Appendectomy.
AB  - Acute renal failure due to bilateral ureteral obstruction is a rare complication
      after appendectomy in children. We report a case of bilateral ureteric
      obstruction in a 14-year-old boy nine days after surgery for an acute
      appendicitis. After saline-filling of the urinary bladder, transabdominal
      ultrasound demonstrated bilateral hydronephrosis of moderate degree. No abscess
      was found with CT but presence of millimetric stones on both distal ureters was
      shown, with bilateral calyceal dilatation. Cystoscopy revealed inflammatory
      changes in the bladder base. Following introduction of bilateral ureteric stents,
      there was rapid normalisation of urinary output and serum creatinine. 

PMID- 26295002
TI  - Lipoma of the Small Intestine: A Cause for Intussusception in Adults.
AB  - Intussusception as a cause of intestinal obstruction in adults is rare. There is
      invariably an underlying pathology which leads to intussusception in adults. A
      case of intussusception in an adult due to a small intestinal lipoma is presented
      in view of this association. Ultrasound and CECT may help in a preoperative
      diagnosis. However early surgical intervention is the mainstay of treatment in
      order to confirm the diagnosis of the underlying pathology, thereby avoiding
      misdiagnosis of an underlying cancer. 

PMID- 26295003
TI  - The Impact of Fracture Incidence on Health Related Quality of Life among
      Community-Based Postmenopausal Women.
AB  - This prospective study aimed to examine the impact of fracture incidence on
      health-related quality of life (HRQOL) among postmenopausal women. Study subjects
      were Australian female community-dwellers in the Global Longitudinal Study of
      Osteoporosis in Women (GLOW). Self-administered questionnaires were collected
      annually from 2007 to 2010. Outcomes were the Medical Outcomes Study Short Form
      36 (SF-36 physical function (SF36PFS) and vitality (SF36VS) scores), European
      Quality of Life (EQ-5D), and self-reported general health (GH) of excellent/good.
      Questionnaires were divided into prior to, the 1st, the 2nd, and the 3rd year
      after incident fracture assessments. Generalized linear models with generalised
      estimating equations (GEE) were employed for the analysis. The 2,872 participants
      (age: median 65; interquartile range 60-73 years) provided a total of 10,436
      assessments including 266, 165 and 76 assessments for the 1st, the 2nd, and the
      3rd year after incident fracture, respectively. Multivariate adjustments showed
      reductions in HRQOL measures peaking at the 1st year for SF36VS (coefficient 
      3.0; 95% CI: -5.1, -0.8) and EQ-5D (coefficient -0.03; 95% CI: -0.06, -0.00) and
      at the 2nd year for SF36PFS (coefficient -3.0; 95% CI: -5.6, -0.5) and GH (odds
      ratio 0.92; 95% CI: 0.70, 1.19). Fracture incidence reduced HRQOL including
      vitality and physical function among relatively young, healthy postmenopausal
      women and the reduction in European Quality of Life measure was clinically
      important. 

PMID- 26295004
TI  - Coagulation and Fibrinolysis Indicators and Placental Malaria Infection in an
      Area Characterized by Unstable Malaria Transmission in Central Sudan.
AB  - This study aimed to investigate coagulation, fibrinolysis indicators, and malaria
      during pregnancy. Methods. A cross-sectional study was conducted at Medani,
      Sudan. Sociodemographic characteristics were gathered from each parturient woman
      (163) and malaria was investigated by blood film and placental histology. Protein
      C, protein S, antithrombin-III, tissue factor pathway inhibitor (TFPI), and
      plasminogen activator inhibitor-1 levels (PAI-1) were measured using ELISA.
      Results. One (0.6%), three (1.8), and 19 (11.7%) of the placentae showed active,
      chronic, and past infection on a histopathological examination, respectively,
      while 140 (85.9%) of them showed no signs of malaria infection. While the mean
      [SD] of the protein C, antithrombin-III, and TFPI was significantly lower, there
      was no significant difference in protein S and PAI-1 levels in women with
      placental malaria infection (n = 23) compared to those without placental malaria
      infection (140). In linear regression, placental malaria infection was associated
      with antithrombin-III. There was no association between placental malaria
      infections and protein C, protein S, TFPI, and PAI-1 levels. There was no
      association between hemoglobin, birth weight, and the investigated coagulation
      and fibrinolysis indicators. Conclusion. This study showed significantly lower
      levels of protein C, antithrombin-III, and TFPI in women with placental malaria
      infections. 

PMID- 26295005
TI  - Deep Brain Stimulation Can Preserve Working Status in Parkinson's Disease.
AB  - Objectives. Our investigation aimed at evaluating if bilateral subthalamic deep
      brain stimulation (DBS) could preserve working capability in Parkinson's disease
      (PD). Materials. We reviewed the data of 40 young (<60 year-old) PD patients who
      underwent DBS implantation and had at least 2 years of follow-up. Patients were
      categorized based on their working capability at time of surgery: "active job"
      group (n = 20) and "no job" group (n = 20). Baseline characteristics were
      comparable. Quality of life (EQ-5D) and presence of active job were evaluated
      preoperatively and 2 years postoperatively. Results. Although similar
      (approximately 50%) improvement was achieved in the severity of motor and major
      nonmotor symptoms in both groups, the postoperative quality of life was
      significantly better in the "active job" group (0.687 versus 0.587, medians, p <
      0.05). Majority (80%) of "active job" group members were able to preserve their
      job 2 years after the operation. However, only a minimal portion (5%) of the "no
      job" group members was able to return to the world of active employees (p <
      0.01). Conclusions. Although our study has several limitations, our results
      suggest that in patients with active job the appropriately "early" usage of DBS
      might help preserve working capability and gain higher improvement in quality of
      life. 

PMID- 26295006
TI  - Motivational Differences between Whole Blood and Apheresis Donors in Quebec,
      Canada: A Questionnaire-Based Survey in a Voluntary Nonremunerated Context.
AB  - Background. Finding ways to recruit apheresis donors is crucial. The aim of this
      study was to provide a quantitative analysis of the motivations of regular
      plasma/platelets donors (PPDs) in comparison with those of regular whole blood
      donors (WBDs), in a voluntary and nonremunerated context. Study Design and
      Methods. Motives to donate blood and demographic characteristics were collected
      through questionnaires completed by 795 WBDs and 473 PPDs. Chi-square tests were
      completed to determine which motivations stand out across the two blood donor
      groups. Results. The motivator selected by the highest percentage was "my blood
      can save lives." Comparison of WBDs and PPDs showed that 12 out of 23 items were
      statistically significantly different from one group to another. Conclusion. The
      belief that helping others is in their nature is more prevalent among PPDs. In
      this sense, their profile is unique. Four other motivators distinguish this group
      from the WBDs: "I think there is a strong need for blood products," "it gives me
      a sense of pride," "I like to have goals," and "I receive telephone reminders."
      These motivators point to the role the ongoing support provided by blood
      collection agencies (BCAs) plays with PPDs. 

PMID- 26295007
TI  - Vigabatrin Retinal Toxicity First Detected with Electroretinographic Changes: A
      Case Report.
AB  - Vigabatrin is an effective antiepileptic drug (AED) typically used in the
      treatment of refractory partial seizures and infantile spasms. Its use, however,
      is limited due to the concern of retinal toxicity and subsequent visual field
      defects. Herewith in we describe a case of vigabatrin toxicity that illustrates
      electroretinographic (ERG) changes occur before imaging and visual field
      deterioration. Decrease in maximal ERG b: a ratio was observed before thinning of
      the retinal nerve fiber layer (RNFL) on optical coherence tomography (OCT).

PMID- 26295008
TI  - Relationship of 1,25 dihydroxy Vitamin D Levels to Clinical Outcomes in
      Critically Ill Patients with Acute Kidney Injury.
AB  - BACKGROUND: Calcitriol [1,25(OH)2D] plays a central role in endocrine regulation
      of bone and mineral metabolism. Low 1,25(OH)2D levels in chronic kidney disease
      (CKD) are associated with increased cardiovascular morbidity and mortality.
      However, the role of 1,25(OH)2D in acute kidney injury (AKI) is unclear, with
      very limited data. This pilot study examined the relationship between 1,25(OH)2D
      levels in critically ill patients with AKI and clinical outcomes. METHODS: Plasma
      1,25(OH)2D, intact parathyroid hormone (iPTH), 25-OH Vitamin D (VitD), calcium
      and phosphorus were measured in 34 patients with AKI without pre-existing chronic
      kidney disease and 12 healthy controls. RESULTS: The mean 1,25(OH)2D levels were
      significantly lower in patients with AKI compared to controls, (42+/-5.6 pg/mL
      vs. 76.1+/-5.3 pg/mL, P <0.0001). The mortality in patients with AKI was 30%.
      1,25(OH)2D levels were higher in non-survivors than survivors (62+/-41.4 pg/mL
      vs. 33.7+/-24.2 pg/mL respectively, P = 0.046) and serum phosphorus was also
      higher in non-survivors (6.2+/-2.1 mg/dL vs. 4.6+/-1.6 mg/dL, P = 0.019).
      However, on multivariate regression analysis, accounting for age and APACHE II
      score, higher levels of 1,25(OH)2D was not associated with mortality in
      critically ill patients with AKI. CONCLUSION: Mineral metabolism is dysregulated
      within days of acute renal injury in critically ill patients. On univariate
      analysis, high levels of calcitriol were associated with adverse clinical outcome
      in AKI. This association was not apparent after adjusting for age and APACHE II.
      Large controlled studies are needed to confirm these results, and determine if
      higher 1,25(OH)2D mediates worse outcomes in AKI.

PMID- 26295009
TI  - Child disaster mental health interventions, part II: Timing of implementation,
      delivery settings and providers, and therapeutic approaches.
AB  - This review summarizes current knowledge on the timing of child disaster mental
      health intervention delivery, the settings for intervention delivery, the
      expertise of providers, and therapeutic approaches. Studies have been conducted
      on interventions delivered during all phases of disaster management from pre
      event through many months post event. Many interventions were administered in
      schools which offer access to large numbers of children. Providers included
      mental health professionals and school personnel. Studies described individual
      and group interventions, some with parent involvement. The next generation of
      interventions and studies should be based on an empirical analysis of a number of
      key areas.

PMID- 26295010
TI  - Racial and Ethnic Disparities in Time to Cure of Incontinence Present at Nursing
      Home Admission.
AB  - As many as half of older people that are admitted to nursing homes (NHs) are
      incontinent of urine and/or feces. Not much is known about the rate of cure of
      incontinence present at NH admission, but available reports suggest the rate is
      low. There have been racial and ethnic disparities in incontinence treatment, but
      the role of disparities in the cure of incontinence is understudied. Using the
      Peters-Belson method and multilevel predictors, our findings showed that there
      were disparities in the time to cure of incontinence for Hispanic NH admissions.
      A significantly smaller proportion of older Hispanic admissions were observed to
      have their incontinence cured and cured later than expected had they been White.
      Reducing disparities in incontinence cure will improve health outcomes of
      Hispanic NH admissions. Significant predictors in our model suggest strategies to
      reduce the disparity including attention to managing fecal incontinence and
      incontinence in those with cognitive impairment, improving residents' functional
      status, and increasing resources to NHs admitting older Hispanics with
      incontinence to develop innovative and cost effective ways to provide equitable
      quality care.

PMID- 26295011
TI  - Health Literate Organizations: Are Clinical Trial Sites Equipped to Recruit
      Minority and Limited Health Literacy Patients?
AB  - BACKGROUND: Racial/ethnic minority patients are less likely than non-Latino white
      patients to participate in cancer clinical trials. A key barrier to participation
      is limited health literacy which is more common among minorities. At the
      organizational level, it is important that clinical trials sites become better
      equipped to recruit minority patients by expanding their organizational health
      literacy including language competency and outreach efforts. We explored the
      characteristics of clinical trial sites that are associated with these health
      literate behaviors. METHODS: We identified 353 breast clinical trials recruiting
      participants in 2006 from four states (California, Florida, Illinois, and New
      York) through the National Cancer Institute Physician Data Query system. From
      October 2008 to November 2009, we contacted one research team member (RTM) from
      each site for a telephone survey to assess the site's health literate
      characteristics. RESULTS: Of 233 RTMs who responded, 93% were female and 89% were
      US-born. Overall, 48% of sites offered supplementary trial information, 80%
      offered materials to assist with patient navigation and 45% reported outreach
      efforts. Lower percentages offered information in other languages while 65%
      offered professional interpretation services. Sites with >10% limited English
      proficiency (LEP) patients were more likely than their counterparts to offer
      consent forms (OR=3.13, 1.36-7.19) and supplementary information about trials in
      other languages (OR=2.52, 1.15-5.52). Sites with diverse patient populations
      (>10% Latino) were also more likely than less diverse sites to engage in outreach
      (OR=1.97, 1.07-3.60), to offer consent forms (OR=2.72, 1.38-5.36), supplementary
      information about trials (OR=2.58, 1.24-5.36), and materials to improve patient
      navigation (OR=2.50, 1.22-5.13) in other languages. CONCLUSIONS: Efforts to
      recruit diverse participants were limited. Practice type and diversity of patient
      population were associated with sites' efforts to accommodate these
      characteristics, suggesting that sites were responsive to the needs of their
      patients when diversity was prevalent.

PMID- 26295012
TI  - Gathering perspectives on extended family influence on African American
      children's physical activity.

PMID- 26295013
TI  - Post-operative Hamman's sign: a case report.
AB  - INTRODUCTION: We provide this brief case report on Hamman's sign, as a reminder
      that both pneumomediastinum and pneumothorax can cause sounds that may disclose
      the abnormal presence of air in these respective locations. BACKGROUND:
      Attributed originally to the observations and report of Louis Hamman in 1937,
      abnormal sounds may emanate from air in the otherwise quiet mediastinum or
      pleural space. CASE PRESENTATION: Our patient, a 36 year old white male, reported
      the occurrence of an abnormal "rhythmic clicking" sound emanating from his upper
      body when lying on his left side, 3 weeks following nasal septal surgery. The
      patient's clear report of particularly loud sounds, beginning post-operatively,
      was corroborated by the patient's wife. A CT scan of the chest which confirmed
      the presence of air in the left pleural space. CONCLUSIONS: The presence of a
      sound, loud enough to be heard at a distance from the patient (corroborated by
      another individual) is unusual. The value of patient history is underscored by
      the finding of a pneumothorax, suggesting Hamman's sign.

PMID- 26295014
TI  - Focal pulmonary interstitial opacities adjacent to the thoracic spine osteophytes
      among the cases with right-sided aortic arch.
AB  - OBJECTIVE: The purpose of this study was to evaluate the factors to development
      of focal pulmonary interstitial opacities adjacent to thoracic spine osteophytes
      among cases with right-sided aortic arch. MATERIALS AND METHODS: This was a
      retrospective review of our hospital information system on patients with right
      sided aortic arch who underwent chest computed tomography (CT) from April 2003 to
      September 2014. CT were reviewed to evaluate the position and thickness of
      osteophytes and that of focal pulmonary opacities adjacent to osteophytes,
      comparing data between the patients with osteophytes with pulmonary opacity
      (group A) and patients with osteophytes without pulmonary opacity (group B).
      RESULTS: There were 25 patients totally, 23 cases of left-sided thoracic
      osteophytes, two cases on both sides. Comparing Group A (n = 10) and Group B (n =
      15), the presence of pulmonary opacities was significantly associated with
      thickness of osteophytes (Mann-Whitney U test, P < 0.05). CONCLUSION: In patients
      with right-sided aortic arch, thoracic osteophytes were often observed on the
      left side. The presence of pulmonary opacities adjacent to thoracic osteophytes
      was associated with thickness of osteophytes. Furthermore, these interstitial
      opacities should not be considered a preclinical form of fibrosing lung disease.

PMID- 26295015
TI  - Comparing determinants of physical activity in Puerto Rican, Mexican-American,
      and non-Hispanic white breast cancer survivors.
AB  - PURPOSE: Physical activity (PA) has a myriad of benefits for breast cancer
      survivors, including a reduced risk of cancer recurrence. Latinas are less
      physically active than are women in the general population and little is known
      about Latina breast cancer survivors' levels of PA or their beliefs related to
      PA. We conducted a survey of 50 Puerto Rican (PR), 50 Mexican-American (MA) and
      50 non-Hispanic white (NHW) breast cancer survivors to investigate similarities
      and differences in PA and social cognitive theory (SCT) constructs associated
      with PA. METHODS: We collected information on current PA using the Godin Leisure
      Time Exercise Questionnaire (GLTEQ); comorbidities; anthropometric measures of
      body mass index [BMI (kg/m(2))] and waist-to-hip (W:H) ratio; and SCT measures,
      including exercise self-efficacy, exercise barriers self-efficacy, modeling and
      social support from friends and family. Descriptive statistics, one-way analysis
      of variance of differences between groups and regression models of the predictors
      of PA were performed. RESULTS: Survivors from the three groups were similar in
      age (M = 56.8, SD = 11.0), BMI (M = 29.0, SD = 5.7) and co-morbidity (M = 2.09,
      SD = 1.69). Survivors differed in PA (p < 0.001), self-efficacy (p = 0.05),
      modeling (p = 0.03) and social support from family (p = 0.05). Social support
      from family member and exercise barriers self-efficacy were predictors of PA.
      CONCLUSIONS: Consistent with published studies, Hispanic breast cancer survivors
      self-report that they are less physically active than are non-Hispanic whites.
      SCT variables associated with PA differ among Hispanic subgroups and non-Hispanic
      whites. Further research is warranted in order to understand determinants of
      physical activity for specific ethnic breast cancer survivors.

PMID- 26295016
TI  - The impact of laparoscopic diverted sleeve gastrectomy with ileal transposition
      (DSIT) on short term diabetic medication costs.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) has gained pandemic proportions
      becoming a global threat within the last few decades. In parallel to the
      increasing prevalence, healthcare costs have become a huge economic burden for
      the hospital and governments. Bariatric surgery has been proven to induce
      glycemic control in obese type 2 diabetics. However, the cost effectiveness of
      metabolic surgery in overweight, obese and morbidly obese individuals has not
      been documented. We aimed to demonstrate the efficacy and reduced diabetic
      medication cost after diverted sleeve gastrectomy with ileal interposition (DSIT)
      in type 2 diabetic individuals followed more than 1 year. METHODS: Records of 116
      type 2 diabetic patients operated by DSIT at a dedicated metabolic surgery clinic
      between October 2011 and April 2013 were retrospectively reviewed. A comparison
      was made between the annual diabetic medication cost before and after surgery
      using the paired t test. The alterations in BMI and HbA1c were recorded and
      analyzed. RESULTS: Diverted sleeve gastrectomy with ileal interposition led to a
      marked reduction in BMI and improved glycemic control after 1 year follow-up.
      Mean HbA1c levels decreased from a mean of 8.9 +/- 1.7 to 6.6 +/- 1.1 1 year
      after surgery (p < 0.001). Mean preoperative BMI declined from 32.9 +/- 4.3  to
      24.7 +/- 2.7 kg/m(2) (p < 0.001). Cost of diabetic medication decreased from a
      mean 660.08 USD/year to 65.12 USD 1 year after surgery (p < 0.001). CONCLUSION:
      Our results have shown that DSIT operation leads to a significantly better
      glycemic control and lower diabetic medication costs at 1 year.

PMID- 26295017
TI  - Update of Adolescent Smoking Cessation Interventions: 2009-2014.
AB  - The treatment of adolescent tobacco dependence is an imperative public health
      goal. Adolescent-focused smoking cessation interventions have shown modest
      results at most, indicating the need for the development of innovative and
      effective interventions for this vulnerable population. This review aims to
      provide an update of smoking cessation interventions for youth by reviewing the
      literature published between 2009 and November 2014 evaluating psychosocial and
      pharmacological interventions. Based on this examination, future directions for
      research in advancing the development of adolescent-focused tobacco treatments
      are provided.

PMID- 26295018
TI  - Prenatal Exposure to Cadmium and Cotinine and CpG island DNA methylation in
      Mother-Infant Pairs.
AB  - A precise biological mechanism by which cadmium acts as a developmental toxicant
      is unknown but is suggested to include an epigenetic basis. In prior work, we
      analyzed CpG island methylation levels within gene promoters (n=16,421) in
      leukocytes collected from mothers and their infants from a pregnancy cohort in
      Durham County, North Carolina. The CpG methylation levels were examined in
      relationship to prenatal exposure to cadmium and/or cotinine to identify genes
      and pathways influenced by in utero exposure. In the present article, we provide
      an enhanced description of the data collection and processing to facilitate cross
      study comparisons. Data are available within the Gene Expression Omnibus database
      (GSE67976).

PMID- 26295019
TI  - Effects of developmental exposure to manganese and/or low iron diet: Changes to
      metal transporters, sucrose preference, elevated zero-maze, open-field, and
      locomotion in response to fenfluramine, amphetamine, and MK-801.
AB  - Manganese overexposure (MnOE) can be neurotoxic. In humans this can occur through
      occupational exposure, air or water contamination, well water, soy milk, and some
      baby formulas. In children MnOE has been associated with cognitive and behavioral
      deficits. The effects of MnOE may be modified by factors such as iron status. We
      hypothesized that developmental MnOE would be exacerbated by iron deficiency. A
      diet with a 90% decrease in iron (FeD) was given to gravid female rats starting
      on embryonic day 15 and continued through postnatal day (P)28. Mn (100 mg/kg) or
      vehicle (VEH) was administered by gavage every other day from P4-28. Metal
      transporters and receptors (divalent metal transporter-1 (DMT1), transferrin
      (Tf), transferrin receptor (TfR), and zip8 (zrt8)) were quantified in brain at
      P28. These markers were increased but the changes were specific: MnOE increased
      TfR and decreased Tf in hippocampus, whereas FeD increased TfR in neostriatum and
      increased TfR and DMT1 in the hippocampus, and the combination increased TfR in
      neostriatum (zip8 was unaffected). Identically treated animals were tested
      behaviorally at P29 or P60. The combination of FeD+MnOE increased head dips in an
      elevated zero-maze, reversed deficits in sucrose preference induced by MnOE
      alone, and increased spontaneous locomotion in an open-field. Rats were also
      evaluated for changes in locomotor activity after challenge with (+/-)
      fenfluramine (FEN, a 5-HT agonist: 5 mg/kg), MK-801 (MK801, an NMDA antagonist:
      0.2 mg/kg), or (+)amphetamine (AMPH, a dopamine agonist: 1 mg/kg). Compared with
      VEH animals, MnOE animals were more hyperactive after fenfluramine, amphetamine,
      or MK-801, regardless of FeD exposure. The results indicate persistent effects of
      developmental MnOE on brain and behavior but few interactions with dietary iron
      deficiency.

PMID- 26295020
TI  - A review of the regenerative endodontic treatment procedure.
AB  - Traditionally, apexification has been used to treat immature permanent teeth that
      have lost pulp vitality. This technique promotes the formation of an apical
      barrier to close the open apex so that the filling materials can be confined to
      the root canal. Because tissue regeneration cannot be achieved with
      apexification, a new technique called regenerative endodontic treatment was
      presented recently to treat immature permanent teeth. Regenerative endodontic
      treatment is a treatment procedure designed to replace damaged pulp tissue with
      viable tissue which restores the normal function of the pulp-dentin structure.
      After regenerative endodontic treatment, continued root development and hard
      tissue deposition on the dentinal wall can occur under ideal circumstances.
      However, it is difficult to predict the result of regenerative endodontic
      treatment. Therefore, the purpose of this study was to summarize multiple factors
      effects on the result of regenerative endodontic treatment in order to achieve
      more predictable results. In this study, we investigated the features of
      regenerative endodontic treatment in comparison with those of other pulp
      treatment procedures and analyzed the factors that have an effect on regenerative
      endodontic treatment. 

PMID- 26295021
TI  - Effect of organic acids in dental biofilm on microhardness of a silorane-based
      composite.
AB  - OBJECTIVES: This study evaluated the effect of lactic acid and acetic acid on the
      microhardness of a silorane-based composite compared to two methacrylate-based
      composite resins. MATERIALS AND METHODS: Thirty disc-shaped specimens each were
      fabricated of Filtek P90, Filtek Z250 and Filtek Z350XT. After measuring of
      Vickers microhardness, they were randomly divided into 3 subgroups (n = 10) and
      immersed in lactic acid, acetic acid or distilled water. Microhardness was
      measured after 48 hr and 7 day of immersion. Data were analyzed using repeated
      measures ANOVA (p < 0.05). The surfaces of two additional specimens were
      evaluated using a scanning electron microscope (SEM) before and after immersion.
      RESULTS: All groups showed a reduction in microhardness after 7 day of immersion
      (p < 0.001). At baseline and 7 day, the microhardness of Z250 was the greatest,
      followed by Z350 and P90 (p < 0.001). At 48 hr, the microhardness values of Z250
      and Z350 were greater than P90 (p < 0.001 for both), but those of Z250 and Z350
      were not significantly different (p = 0.095). Also, the effect of storage media
      on microhardness was not significant at baseline, but significant at 48 hr and
      after 7 day (p = 0.001 and p < 0.001, respectively). Lactic acid had the greatest
      effect. CONCLUSIONS: The microhardness of composites decreased after 7 day of
      immersion. The microhardness of P90 was lower than that of other composites.
      Lactic acid caused a greater reduction in microhardness compared to other
      solutions.

PMID- 26295023
TI  - Effects of solvent volatilization time on the bond strength of etch-and-rinse
      adhesive to dentin using conventional or deproteinization bonding techniques.
AB  - OBJECTIVES: This study determined the effect of the air-stream application time
      and the bonding technique on the dentin bond strength of adhesives with different
      solvents. Furthermore, the content and volatilization rate of the solvents
      contained in the adhesives were also evaluated. MATERIALS AND METHODS: Three
      adhesive systems with different solvents (Stae, SDI, acetone; XP Bond, Dentsply
      De Trey, butanol; Ambar, FGM, ethanol) were evaluated. The concentrations and
      evaporation rates of each adhesive were measured using an analytical balance.
      After acid-etching and rinsing, medium occlusal dentin surfaces of human molars
      were kept moist (conventional) or were treated with 10% sodium hypochlorite for
      deproteinization. After applying adhesives over the dentin, slight air-stream was
      applied for 10, 30 or 60 sec. Composite cylinders were built up and submitted to
      shear testing. The data were submitted to ANOVA and Tukey's test (alpha = 0.05).
      RESULTS: Stae showed the highest solvent content and Ambar the lowest. Acetone
      presented the highest evaporation rate, followed by butanol. Shear bond strengths
      were significantly affected only by the factors of 'adhesive' and 'bonding
      technique' (p < 0.05), while the factor 'duration of air-stream' was not
      significant. Deproteinization of dentin increased the bond strength (p < 0.05).
      Stae showed the lowest bond strength values (p < 0.05), while no significant
      difference was observed between XP Bond and Ambar. CONCLUSIONS: Despite the
      differences in content and evaporation rate of the solvents, the duration of air
      stream application did not affect the bond strength to dentin irrespective of the
      bonding technique.

PMID- 26295022
TI  - Chelating and antibacterial properties of chitosan nanoparticles on dentin.
AB  - OBJECTIVES: The use of chitosan nanoparticles (CNPs) in endodontics is of
      interest due to their antibiofilm properties. This study was to investigate the
      ability of bioactive CNPs to remove the smear layer and inhibit bacterial
      recolonization on dentin. MATERIALS AND METHODS: One hundred bovine dentin
      sections were divided into five groups (n = 20 per group) according to the
      treatment. The irrigating solutions used were 2.5% sodium hypochlorite (NaOCl)
      for 20 min, 17% ethylenediaminetetraacetic acid (EDTA) for 3 min and 1.29 mg/mL
      CNPs for 3 min. The samples were irrigated with either distilled water (control),
      NaOCl, NaOCl-EDTA, NaOCl-EDTA-CNPs or NaOCl-CNPs. After the treatment, half of
      the samples (n = 50) were used to assess the chelating effect of the solutions
      using portable scanning electronic microscopy, while the other half (n = 50) were
      infected intra-orally to examine the post-treatment bacterial biofilm forming
      capacity. The biovolume and cellular viability of the biofilms were analysed
      under confocal laser scanning microscopy. The Kappa test was performed for
      examiner calibration, and the non-parametric Kruskal-Wallis and Dunn tests (p <
      0.05) were used for comparisons among the groups. RESULTS: The smear layer was
      significantly reduced in all of the groups except the control and NaOCl groups (p
      < 0.05). The CNPs-treated samples were able to resist biofilm formation
      significantly better than other treatment groups (p < 0.05). CONCLUSIONS: CNPs
      could be used as a final irrigant during root canal treatment with the dual
      benefit of removing the smear layer and inhibiting bacterial recolonization on
      root dentin.

PMID- 26295024
TI  - Do conventional glass ionomer cements release more fluoride than resin-modified
      glass ionomer cements?
AB  - OBJECTIVES: The aim of this study was to evaluate the fluoride release of
      conventional glass ionomer cements (GICs) and resin-modified GICs. MATERIALS AND
      METHODS: The cements were grouped as follows: G1 (Vidrion R, SS White), G2 (Vitro
      Fil, DFL), G3 (Vitro Molar, DFL), G4 (Bioglass R, Biodinamica), and G5 (Ketac
      Fil, 3M ESPE), as conventional GICs, and G6 (Vitremer, 3M ESPE), G7 (Vitro Fil
      LC, DFL), and G8 (Resiglass, Biodinamica) as resin-modified GICs. Six specimens
      (8.60 mm in diameter; 1.65 mm in thickness) of each material were prepared using
      a stainless steel mold. The specimens were immersed in a demineralizing solution
      (pH 4.3) for 6 hr and a remineralizing solution (pH 7.0) for 18 hr a day. The
      fluoride ions were measured for 15 days. Analysis of variance (ANOVA) and Tukey's
      test with 5% significance were applied. RESULTS: The highest amounts of fluoride
      release were found during the first 24 hr for all cements, decreasing abruptly on
      day 2, and reaching gradually decreasing levels on day 7. Based on these results,
      the decreasing scale of fluoride release was as follows: G2 > G3 > G8 = G4 = G7 >
      G6 = G1 > G5 (p < 0.05). CONCLUSIONS: There were wide variations among the
      materials in terms of the cumulative amount of fluoride ion released, and the
      amount of fluoride release could not be attributed to the category of cement,
      that is, conventional GICs or resin-modified GICs.

PMID- 26295025
TI  - Evaluation of the effects of two novel irrigants on intraradicular dentine
      erosion, debris and smear layer removal.
AB  - OBJECTIVES: To evaluate the effects of copolymer of acrylic acid and maleic acid
      (Poly[AA-co-MA]) and calcium hypochlorite (Ca(OCl)2) on root canal dentin using
      scanning electron microscope (SEM). MATERIALS AND METHODS: Twenty-four single
      rooted teeth were instrumented and the apical and coronal thirds of each root
      were removed, leaving the 5 mm middle thirds, which were then separated into two
      pieces longitudinally. The specimens were randomly divided into six groups and
      subjected to each irrigant for 5 min as follows: G1, Ca(OCl)2; G2, Poly(AA-co
      MA); G3, Ca(OCl)2 + Poly(AA-co-MA); G4, sodium hypochlorite (NaOCl); G5,
      ethylenediaminetetraacetic acid (EDTA); G6, NaOCl+EDTA. The specimens were
      prepared for SEM evaluation. Smear layer, debris and erosion scores were recorded
      by two blinded examiners. One image from G3 was analyzed with energy dispersive
      spectroscopy (EDS) on suspicion of precipitate formation. Data were analyzed
      using the Kruskal-Wallis and Dunn tests. RESULTS: G1 and G4 showed the presence
      of debris and smear layer and they were statistically different from G2, G3, G5
      and G6 where debris and smear layer were totally removed (p < 0.05). In G1 and
      G4, erosion evaluation could not be done because of debris and smear layer. G2,
      G3 and G5 showed no erosion, and there was no significant difference between
      them. G6 showed severe erosion and was statistically different from G2, G3 and G5
      (p < 0.05). EDS microanalysis showed the presence of Na, P, and Ca elements on
      the surface. CONCLUSIONS: Poly(AA-co-MA) is effective in removing the smear layer
      and debris without causing erosion either alone or with Ca(OCl)2.

PMID- 26295026
TI  - Changes in SIRT gene expression during odontoblastic differentiation of human
      dental pulp cells.
AB  - OBJECTIVES: The aim of this study was to investigate the expression of 7
      different sirtuin genes (SIRT1-SIRT7) in human dental pulp cells (HDPCs), and to
      determine the role of SIRTs in the odontoblastic differentiation potential of
      HDPCs. MATERIALS AND METHODS: HDPCs were isolated from freshly extracted third
      molar teeth of healthy patients and cultulred in odontoblastic differentiation
      inducing media. Osteocalcin (OCN) and dentin sialophosphoprotein (DSPP)
      expression was analyzed to evaluate the odontoblastic differentiation of HDPCs by
      reverse transcription-polymerase chain reaction (RT-PCR), while alizarin red
      staining was used for the mineralization assay. To investigate the expression of
      SIRTs during odontoblastic differentiation of HDPCs, real time PCR was also
      performed with RT-PCR. RESULTS: During the culture of HDPCs in the
      differentiation inducing media, OCN, and DSPP mRNA expressions were increased.
      Mineralized nodule formation was also increased in the 14 days culture. All seven
      SIRT genes were expressed during the odontogenic induction period. SIRT4
      expression was increased in a time-dependent manner. CONCLUSIONS: Our study
      identified the expression of seven different SIRT genes in HDPCs, and revealed
      that SIRT4 could exert an influence on the odontoblast differentiation process.
      Further studies are needed to determine the effects of other SIRTs on the
      odontogenic potential of HDPCs.

PMID- 26295027
TI  - Fracture resistance of upper central incisors restored with different posts and
      cores.
AB  - OBJECTIVES: To determine and compare the fracture resistance of endodontically
      treated maxillary central incisors restored with different posts and cores.
      MATERIALS AND METHODS: Forty-eight upper central incisors were randomly divided
      into four groups: cast post and core (group 1), fiber-reinforced composite (FRC)
      post and composite core (group 2), composite post and core (group 3), and
      controls (group 4). Mesio-distal and bucco-lingual dimensions at 7 and 14 mm from
      the apex were compared to ensure standardization among the groups. Twelve teeth
      were prepared for crown restoration (group 4). Teeth in other groups were
      endodontically treated, decoronated at 14 mm from the apex, and prepared for
      posts and cores. Resin-based materials were used for cementation in groups 1 and
      2. In group 3, composite was used directly to fill the post space and for core
      build-up. All samples were restored by standard metal crowns using glass ionomer
      cement, mounted at 135 degrees  vertical angle, subjected to thermomechanical
      aging, and then fractured using a universal testing machine. Kruskal-Wallis and
      Mann-Whitney U tests were used to analyze the data. RESULTS: Fracture resistance
      of the groups was as follows: Control (group 4) > cast post and core (group 1) >
      fiber post and composite core (group 2) > composite post and core (group 3). All
      samples in groups 2 and 3 fractured in restorable patterns, whereas most (58%) in
      group 1 were non-restorable. CONCLUSIONS: Within the limitations of this study,
      FRC posts showed acceptable fracture resistance with favorable fracture patterns
      for reconstruction of upper central incisors.

PMID- 26295028
TI  - Autotransplantation combined with orthodontic treatment: a case involving the
      maxillary central incisors with root resorption after traumatic injury.
AB  - Traumatic dental injury can result in avulsion of anterior teeth. In young
      patients, it is a challenge to the dental professional because after
      replantation, late complications such as ankylosis require tooth extraction.
      Although prosthetic and orthodontic treatment, and implant placement have been
      described as the options for intervention, autogenous tooth transplantation could
      be an effective procedure in growing patients if there is a suitable donor tooth
      available. This case presents the treatment of a patient who suffered a traumatic
      injury at 9 years old with avulsion of tooth 21, which had been replanted, and
      intrusion of tooth 11. Both teeth ankylosed; thus they were removed and
      autotransplantation of premolars was carried out. After transplantation, the
      tooth underwent root canal treatment because of pulpal necrosis. Orthodontic
      treatment began 3 months after transplantation and during 7 years' follow-up the
      aesthetics and function were maintained without signs of resorption. 

PMID- 26295029
TI  - Endodontic management of a maxillary first molar with three roots and seven root
      canals with the aid of cone-beam computed tomography.
AB  - Variation in root canal morphology, especially in maxillary first molar presents
      a constant challenge for a clinician in their detection and management. This case
      report describes the successful root canal treatment of a three rooted right
      maxillary first molar presenting with three canals each in the mesiobuccal and
      distobuccal roots and one canal in the palatal root. The clinical detection of
      this morphologic aberration was made using a dental operating microscope, and the
      canal configuration was established after correlating and computing the clinical,
      radiographic and cone-beam computed tomography (CBCT) scan findings. CBCT images
      confirmed the configuration of the canals in the mesiobuccal and distobuccal
      roots to be Al-Qudah and Awawdeh type (3-2) and type (3-2-1), respectively,
      whereas the palatal root had a Vertucci type I canal pattern. This report
      reaffirms the importance of careful examination of the floor of the pulp chamber
      with a dental operating microscope and the use of multiangled preoperative
      radiographs along with advanced diagnostic aids such as CBCT in identification
      and successful management of aberrant canal morphologies. 

PMID- 26295030
TI  - Statistical notes for clinical researchers: Type I and type II errors in
      statistical decision.

PMID- 26295031
TI  - Safe root canal preparation using reciprocating nickel-titanium instruments.

PMID- 26295032
TI  - Heavy Metal Adsorption onto Kappaphycus sp. from Aqueous Solutions: The Use of
      Error Functions for Validation of Isotherm and Kinetics Models.
AB  - Biosorption process is a promising technology for the removal of heavy metals
      from industrial wastes and effluents using low-cost and effective biosorbents. In
      the present study, adsorption of Pb(2+), Cu(2+), Fe(2+), and Zn(2+) onto dried
      biomass of red seaweed Kappaphycus sp. was investigated as a function of pH,
      contact time, initial metal ion concentration, and temperature. The experimental
      data were evaluated by four isotherm models (Langmuir, Freundlich, Temkin, and
      Dubinin-Radushkevich) and four kinetic models (pseudo-first-order, pseudo-second
      order, Elovich, and intraparticle diffusion models). The adsorption process was
      feasible, spontaneous, and endothermic in nature. Functional groups in the
      biomass involved in metal adsorption process were revealed as carboxylic and
      sulfonic acids and sulfonate by Fourier transform infrared analysis. A total of
      nine error functions were applied to validate the models. We strongly suggest the
      analysis of error functions for validating adsorption isotherm and kinetic models
      using linear methods. The present work shows that the red seaweed Kappaphycus sp.
      can be used as a potentially low-cost biosorbent for the removal of heavy metal
      ions from aqueous solutions. Further study is warranted to evaluate its
      feasibility for the removal of heavy metals from the real environment. 

PMID- 26295033
TI  - Intellectual Impairment in Patients with Newly Diagnosed HIV Infection in
      Southwestern Nigeria.
AB  - Neurocognitive impairment is a detrimental complication of HIV infection. Here,
      we characterized the intellectual performance of patients with newly diagnosed
      HIV infection in southwestern Nigeria. We conducted a prospective study at Owo
      Federal Medical Center by using the adapted Wechsler Adult Intelligence Scale
      (WAIS). The raw scores were converted to standardized scores (z-scores) and
      correlated with clinical and laboratory findings. Fifty-eight HIV positive
      patients were recruited; 72% were in WHO stages 3 and 4. We detected a high rate
      of intellectual impairment in HIV positive patients and controls (63.8% and 10%,
      resp.; P < 0.001). HIV positive patients performed worse throughout the subtests
      of both verbal and performance intelligence quotients. Presence of opportunistic
      infections was associated with worse performance in the similarities and digit
      symbol tests and performance and full scale scores. Lower body weight correlated
      with poor performance in different WAIS subtests. The high rate of advanced
      disease stage warrants measures aimed at earlier diagnosis and treatment.
      Assessment of neurocognitive performance at diagnosis may offer the opportunity
      to improve functioning in daily life and counteract disease progression. 

PMID- 26295034
TI  - CCL27: Novel Cytokine with Potential Role in Pathogenesis of Multiple Sclerosis.
AB  - Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease of unknown
      etiology. Leukocyte infiltration of brain tissue and the subsequent inflammation,
      demyelination, axonal damage, and formation of sclerotic plaques is a hallmark of
      MS. Upregulation of proinflammatory cytokines has been suggested to play an
      essential role in regulating lymphocyte migration in MS. Here we present data on
      serum cytokine expression in MS cases. Increased serum levels of IL-17 and IL-23
      were observed, suggesting activation of the Th17 population of immune effector
      cells. Additionally, increased levels of IL-22 were observed in the serum of
      those with acute phase MS. Unexpectedly, we observed an upregulation of the serum
      chemokine CCL27 in newly diagnosed and acute MS cases. CCL27 is an inflammatory
      chemokine associated with homing of memory T cells to sites of inflammation.
      Therefore, its upregulation in association with MS suggests a potential role in
      disease pathogenesis. Our data supports previous reports showing IL-17 and -23
      upregulation in association with MS and potentially identify a previously unknown
      involvement for CCL27. 

PMID- 26295036
TI  - Oligoclonal Bands in Cerebrospinal Fluid of Black Patients with Multiple
      Sclerosis.
AB  - Genetic susceptibility is a well-recognized factor in the onset of multiple
      sclerosis (MS). The objective of this study was to determine the frequency of
      oligoclonal bands (OCB) restricted to the cerebrospinal fluid, in an ethnically
      mixed group of MS patients in the city of Sao Paulo, Brazil. Techniques used to
      detect OCB consisted of isoelectric focusing followed by immunoblotting. OCB were
      found in 49 (54.4%) out of 90 patients with clinically definite MS; out of the 23
      brown/black patients, 17 (73.9%) were OCB+; out of the 66 white patients, 32
      (48.5%) were OCB+; and the only patient yellow was OCB+ (p = 0.05). Analysis of
      the IgG index was also consistent with the findings, but with lower statistical
      significance. The data presented in our study show that the ethnic differences in
      MS extend to the immune response. 

PMID- 26295035
TI  - An Overview of Potential Targets for Treating Amyotrophic Lateral Sclerosis and
      Huntington's Disease.
AB  - Neurodegenerative diseases affect millions of people worldwide. Progressive
      damage or loss of neurons, neurodegeneration, has severe consequences on the
      mental and physical health of a patient. Despite all efforts by scientific
      community, there is currently no cure or manner to slow degeneration progression.
      We review some treatments that attempt to prevent the progress of some of major
      neurodegenerative diseases: Amyotrophic Lateral Sclerosis and Huntington's
      disease. 

PMID- 26295038
TI  - Applications of Environmental Epidemiology in Addressing Public Health Challenges
      in East Asia.

PMID- 26295037
TI  - Pulmonary Responses of Sprague-Dawley Rats in Single Inhalation Exposure to
      Graphene Oxide Nanomaterials.
AB  - Graphene is receiving increased attention due to its potential widespread
      applications in future. However, the health effects of graphene have not yet been
      well studied. Therefore, this study examined the pulmonary effects of graphene
      oxide using male Sprague-Dawley rats and a single 6-hour nose-only inhalation
      technique. Following the exposure, the rats were allowed to recover for 1 day, 7
      days, or 14 days. A total of three groups were compared: control (fresh air), low
      concentration (0.46 +/- 0.06 mg/m(3)), and high concentration (3.76 +/- 0.24
      mg/m(3)). The exposure to graphene oxide did not induce significant changes in
      the body weights, organ weights, and food consumption during the 14 days of
      recovery time. The microalbumin and lactate dehydrogenase levels in the
      bronchoalveolar lavage (BAL) fluid were not significantly changed due to the
      exposure. Similarly, total cell count, macrophages, polymorphonuclear leukocytes,
      and lymphocytes were not significantly altered in the BAL fluid. Plus, the
      histopathological examination of the rat lungs only showed an uptake of graphene
      oxide in the alveolar macrophages of the high-concentration group. Therefore,
      these results demonstrate that the single inhalation exposure to graphene oxide
      induce minimal toxic responses in rat lungs at the concentrations and time points
      used in the present study.

PMID- 26295039
TI  - Neuroinflammation and Neurodegeneration: Pinpointing Pathological and
      Pharmacological Targets.

PMID- 26295040
TI  - S100B Inhibitor Pentamidine Attenuates Reactive Gliosis and Reduces Neuronal Loss
      in a Mouse Model of Alzheimer's Disease.
AB  - Among the different signaling molecules released during reactive gliosis
      occurring in Alzheimer's disease (AD), the astrocyte-derived S100B protein plays
      a key role in neuroinflammation, one of the hallmarks of the disease. The use of
      pharmacological tools targeting S100B may be crucial to embank its effects and
      some of the pathological features of AD. The antiprotozoal drug pentamidine is a
      good candidate since it directly blocks S100B activity by inhibiting its
      interaction with the tumor suppressor p53. We used a mouse model of amyloid beta-
      (Abeta-) induced AD, which is characterized by reactive gliosis and
      neuroinflammation in the brain, and we evaluated the effect of pentamidine on the
      main S100B-mediated events. Pentamidine caused the reduction of glial fibrillary
      acidic protein, S100B, and RAGE protein expression, which are signs of reactive
      gliosis, and induced p53 expression in astrocytes. Pentamidine also reduced the
      expression of proinflammatory mediators and markers, thus reducing
      neuroinflammation in AD brain. In parallel, we observed a significant
      neuroprotection exerted by pentamidine on CA1 pyramidal neurons. We demonstrated
      that pentamidine inhibits Abeta-induced gliosis and neuroinflammation in an
      animal model of AD, thus playing a role in slowing down the course of the
      disease. 

PMID- 26295041
TI  - Application and Progress of Combined Mesenchymal Stem Cell Transplantation in the
      Treatment of Ischemic Cardiomyopathy.
AB  - Treatment of ischemic cardiomyopathy caused by myocardial infarction (MI) using
      mesenchymal stem cell (MSC) transplantation is a widely researched field, with
      promising clinical application. However, the low survival rate of transplanted
      cells has a severe impact on treatment outcome. Currently, research is focused on
      investigating the strategy of combining genetic engineering, tissue engineering
      materials, and drug/hypoxia preconditioning to improve ischemic cardiomyopathy
      treatment outcome using MSC transplantation treatment (MSCTT). This review
      discusses the application and progress of these techniques. 

PMID- 26295042
TI  - Multicontrast MRI Quantification of Focal Inflammation and Degeneration in
      Multiple Sclerosis.
AB  - INTRODUCTION: Local microstructural pathology in multiple sclerosis patients
      might influence their clinical performance. This study applied multicontrast MRI
      to quantify inflammation and neurodegeneration in MS lesions. We explored the
      impact of MRI-based lesion pathology in cognition and disability. METHODS: 36
      relapsing-remitting MS subjects and 18 healthy controls underwent neurological,
      cognitive, behavioural examinations and 3 T MRI including (i) fluid attenuated
      inversion recovery, double inversion recovery, and magnetization-prepared
      gradient echo for lesion count; (ii) T1, T2, and T2(*) relaxometry and
      magnetisation transfer imaging for lesion tissue characterization. Lesions were
      classified according to the extent of inflammation/neurodegeneration. A
      generalized linear model assessed the contribution of lesion groups to clinical
      performances. RESULTS: Four lesion groups were identified and characterized by
      (1) absence of significant alterations, (2) prevalent inflammation, (3)
      concomitant inflammation and microdegeneration, and (4) prevalent tissue loss.
      Groups 1, 3, 4 correlated with general disability (Adj-R (2) = 0.6; P = 0.0005),
      executive function (Adj-R (2) = 0.5; P = 0.004), verbal memory (Adj-R (2) = 0.4;
      P = 0.02), and attention (Adj-R (2) = 0.5; P = 0.002). CONCLUSION: Multicontrast
      MRI provides a new approach to infer in vivo histopathology of plaques. Our
      results support evidence that neurodegeneration is the major determinant of
      patients' disability and cognitive dysfunction.

PMID- 26295043
TI  - Mmu-miR-27a-5p-Dependent Upregulation of MCPIP1 Inhibits the Inflammatory
      Response in LPS-Induced RAW264.7 Macrophage Cells.
AB  - Lipopolysaccharide (LPS) stimulates macrophages to release proinflammatory
      cytokines. MicroRNAs (miRNAs) are short noncoding RNAs that are involved in
      inflammatory reaction. Our previously study identified the downregulated
      expression of mmu-miR-27a-5p in RAW267.4 cells treated with LPS. To dissect the
      mechanism that mmu-miR-27a-5p regulates target genes and affects proinflammatory
      cytokine secretion more clearly, based on previous bioinformatics prediction
      data, one of the potential target genes, MCPIP1 was observed to be upregulated
      with qRT-PCR and western blot. Luciferase reporter assays were performed to
      further confirm in silico prediction and determine that MCPIP1 is the target of
      mmu-miR-27-5p. The results suggested that mmu-miR-27a-5p directly targeted the 3'
      UTR of MCPIP1 and the interaction between mmu-miR-27-5p and the 3'-UTR of MCPIP1
      is sequence-specific. MCPIP1 overexpression decreased the secretion of IL-6, IL
      1beta, and IL-10 in macrophage cells stimulated with LPS. Our findings may
      provide the important information for the precise roles of mmu-miR-27a-5p in the
      macrophage inflammatory response to LPS stimulation in the future. 

PMID- 26295045
TI  - A Comparison of Food Supply from 1984 to 2009 and Degree of Dietary
      Westernization in Taiwan with Asian Countries and World Continents.
AB  - OBJECTIVE: To compare quality, quantity, and trends of food supply from 1984 to
      2009 and degree of food westernization in Taiwan with Asian countries and world
      continents by using food balance data. METHODS: We compiled data from food
      balance sheets of Taiwan and Food and Agriculture Organization, including five
      continents and three most populated countries each in Eastern, Southern, and
      Southeastern Asia over the period 1984-2009. Quantity of food supply per capita
      was referenced to Taiwan food guides. The population-weighted means of food
      supply from Europe, North America, South America, and Australia and New Zealand
      continents in terms of energy and nutrient distributions, animal/plant sources,
      and sugar/alcohol contribution were used as indicators of westernization. Trends
      of food supply per capita of six food groups were plotted, and linear regression
      was applied to evaluate food changes. FINDINGS: Taiwan's food supply provided
      sufficient quantity in food energy, with the lowest cereals/roots supply and rice
      to wheat ratio, but the highest meat and oil supplies per capita among the 10
      studied Asian countries. Taiwan food supply showed the most westernization among
      these countries. CONCLUSION: Food supply of Taiwan, although currently
      sufficient, indicated some security problems and high tendency of diet
      westernization.

PMID- 26295046
TI  - Spatial Variation of the Relationship between PM 2.5 Concentrations and
      Meteorological Parameters in China.
AB  - Epidemiological studies around the world have reported that fine particulate
      matter (PM2.5) is closely associated with human health. The distribution of PM2.5
      concentrations is influenced by multiple geographic and socioeconomic factors.
      Using a remote-sensing-derived PM2.5 dataset, this paper explores the
      relationship between PM2.5 concentrations and meteorological parameters and their
      spatial variance in China for the period 2001-2010. The spatial variations of the
      relationships between the annual average PM2.5, the annual average precipitation
      (AAP), and the annual average temperature (AAT) were evaluated using the
      Geographically Weighted Regression (GWR) model. The results indicated that PM2.5
      had a strong and stable correlation with meteorological parameters. In
      particular, PM2.5 had a negative correlation with precipitation and a positive
      correlation with temperature. In addition, the relationship between the variables
      changed over space, and the strong negative correlation between PM2.5 and the AAP
      mainly appeared in the warm temperate semihumid region and northern subtropical
      humid region in 2001 and 2010, with some localized differences. The strong
      positive correlation between the PM2.5 and the AAT mainly occurred in the mid
      temperate semiarid region, the humid, semihumid, and semiarid warm temperate
      regions, and the northern subtropical humid region in 2001 and 2010. 

PMID- 26295044
TI  - Insights into Neuroinflammation in Parkinson's Disease: From Biomarkers to Anti
      Inflammatory Based Therapies.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disorder
      worldwide, being characterized by the progressive loss of dopaminergic neurons in
      the substantia nigra pars compacta. Among several putative factors that may
      contribute to PD pathogenesis, inflammatory mechanisms may play a pivotal role.
      The involvement of microglial activation as well as of brain and peripheral
      immune mediators in PD pathophysiology has been reported by clinical and
      experimental studies. These inflammatory biomarkers evaluated by imaging
      techniques and/or by biological sample analysis have become valuable tools for PD
      diagnosis and prognosis. Regardless of the significant increase in the number of
      people suffering from PD, there are still no established disease-modifying or
      neuroprotective therapies for it. There is growing evidence of protective effect
      of anti-inflammatory drugs on PD development. Herein, we reviewed the current
      literature regarding the central nervous system and peripheral immune biomarkers
      in PD and advances in diagnostic and prognostic tools as well as the
      neuroprotective effects of anti-inflammatory therapies. 

PMID- 26295047
TI  - Advanced Computational Approaches for Medical Genetics and Genomics.

PMID- 26295048
TI  - The Effects of Dorsal Cortical Comminution on Radiographic Results following
      Percutaneous Pinning for Extra-Articular Colles' Fracture.
AB  - A number of studies have demonstrated that dorsal cortical comminution (DCC) can
      predict redisplacement after nonoperative treatment of Colles' fractures;
      however, the effects of a DCC defect on radiographic outcomes following
      percutaneous pinning for dorsally displaced extraarticular Colles' fractures are
      unclear. We, therefore, performed a retrospective study on 85 patients who
      sustained such fractures treated with percutaneous pinning within 2006-2009. The
      main outcome measures included four radiographic parameters, including radial
      height, radial inclination, radial tilt, and ulnar variance. The radiological
      results showed that all fractures after percutaneous pinning followed the same
      time series changes and patterns of fracture collapse regardless of the presence
      of a DCC defect. The use of the pinning construct is to provide support for
      static loading but not for dynamic loading. Although the final radiographic
      outcomes were classified as acceptable in fractures with and without DCC, we
      recommend that a different approach in the management of displaced Colles'
      fractures might be necessary in consideration of increasing patient expectations
      of health care. 

PMID- 26295049
TI  - All Three Rows of Outer Hair Cells Are Required for Cochlear Amplification.
AB  - In the mammalian auditory system, the three rows of outer hair cells (OHCs)
      located in the cochlea are thought to increase the displacement amplitude of the
      organ of Corti. This cochlear amplification is thought to contribute to the high
      sensitivity, wide dynamic range, and sharp frequency selectivity of the hearing
      system. Recent studies have shown that traumatic stimuli, such as noise exposure
      and ototoxic acid, cause functional loss of OHCs in one, two, or all three rows.
      However, the degree of decrease in cochlear amplification caused by such
      functional losses remains unclear. In the present study, a finite element model
      of a cross section of the gerbil cochlea was constructed. Then, to determine
      effects of the functional losses of OHCs on the cochlear amplification, changes
      in the displacement amplitude of the basilar membrane (BM) due to the functional
      losses of OHCs were calculated. Results showed that the displacement amplitude of
      the BM decreases significantly when a single row of OHCs lost its function,
      suggesting that all three rows of OHCs are required for cochlear amplification. 

PMID- 26295050
TI  - Neck Circumference as a Predictive Indicator of CKD for High Cardiovascular Risk
      Patients.
AB  - BACKGROUND: Neck circumference (NC) is an anthropometric measure of obesity for
      upper subcutaneous adipose tissue distribution which is associated with
      cardiometabolic risk. This study investigated whether NC is associated with
      indicators of chronic kidney disease (CKD) for high cardiometabolic risk
      patients. METHODS: A total of 177 consecutive patients who underwent the
      outpatient departments of cardiology were prospectively enrolled in the study.
      The patients were aged >20 years with normal renal function or with stages 1-4
      CKD. A linear regression was performed using the Enter method to present an
      unadjusted R(2), standardized coefficients, and standard error, and the Durbin
      Watson test was used to assess residual independence. RESULTS: Most
      anthropometric measurements from patients aged ? 65 were lower than those from
      patients aged < 65, except for women's waist circumference (WC) and waist hip
      ratio. Female NC obtained the highest R(2) values for 24 hr CCR, uric acid,
      microalbuminuria, hsCRP, triglycerides, and HDL compared to BMI, WC, and hip
      circumference. The significances of female NC with 24 hr CCR and uric acid were
      improved after adjusted age and serum creatinine. CONCLUSIONS: NC is associated
      with indicators of CKD for high cardiometabolic risk patients and can be
      routinely measured as easy as WC in the future.

PMID- 26295052
TI  - Spine and Rheumatic Diseases.

PMID- 26295051
TI  - Cocaine Causes Apoptotic Death in Rat Mesencephalon and Striatum Primary
      Cultures.
AB  - To study cocaine's toxic effects in vitro, we have used primary mesencephalic and
      striatal cultures from rat embryonic brain. Treatment with cocaine causes a
      dramatic increase in DNA fragmentation in both primary cultures. The toxicity
      induced by cocaine was paralleled with a concomitant decrease in the microtubule
      associated protein 2 (MAP2) and/or neuronal nucleus protein (NeuN) staining. We
      also observed in both cultures that the cell death caused by cocaine was induced
      by an apoptotic mechanism, confirmed by TUNEL assay. Therefore, the present paper
      shows that cocaine causes apoptotic cell death and inhibition of the neurite
      prolongation in striatal and mesencephalic cell culture. These data suggest that
      if similar neuronal damage could be produced in the developing human brain, it
      could account for the qualitative or quantitative defects in neuronal pathways
      that cause a major handicap in brain function following prenatal exposure to
      cocaine. 

PMID- 26295053
TI  - Association of Environmental Arsenic Exposure, Genetic Polymorphisms of
      Susceptible Genes, and Skin Cancers in Taiwan.
AB  - Deficiency in the capability of xenobiotic detoxification and arsenic methylation
      may be correlated with individual susceptibility to arsenic-related skin cancers.
      We hypothesized that glutathione S-transferase (GST M1, T1, and P1), reactive
      oxygen species (ROS) related metabolic genes (NQO1, EPHX1, and HO-1), and DNA
      repair genes (XRCC1, XPD, hOGG1, and ATM) together may play a role in arsenic
      induced skin carcinogenesis. We conducted a case-control study consisting of 70
      pathologically confirmed skin cancer patients and 210 age and gender matched
      participants with genotyping of 12 selected polymorphisms. The skin cancer risks
      were estimated by odds ratio (OR) and 95% confidence interval (CI) using logistic
      regression. EPHX1 Tyr113His, XPD C156A, and GSTT1 null genotypes were associated
      with skin cancer risk (OR = 2.99, 95% CI = 1.01-8.83; OR = 2.04, 95% CI = 0.99
      4.27; OR = 1.74, 95% CI = 1.00-3.02, resp.). However, none of these polymorphisms
      showed significant association after considering arsenic exposure status.
      Individuals carrying three risk polymorphisms of EPHX1 Tyr113His, XPD C156A, and
      GSTs presented a 400% increased skin cancer risk when compared to those with less
      than or equal to one polymorphism. In conclusion, GSTs, EPHX1, and XPD are
      potential genetic factors for arsenic-induced skin cancers. The roles of these
      genes for arsenic-induced skin carcinogenesis need to be further evaluated. 

PMID- 26295056
TI  - Automated Audiovisual Depression Analysis.
AB  - Analysis of observable behavior in depression primarily relies on subjective
      measures. New computational approaches make possible automated audiovisual
      measurement of behaviors that humans struggle to quantify (e.g., movement
      velocity and voice inflection). These tools have the potential to improve
      screening and diagnosis, identify new behavioral indicators of depression,
      measure response to clinical intervention, and test clinical theories about
      underlying mechanisms. Highlights include a study that measured the temporal
      coordination of vocal tract and facial movements, a study that predicted which
      adolescents would go on to develop depression based on their voice qualities, and
      a study that tested the behavioral predictions of clinical theories using
      automated measures of facial actions and head motion.

PMID- 26295054
TI  - Cross Talk between Lipid Metabolism and Inflammatory Markers in Patients with
      Diabetic Retinopathy.
AB  - PURPOSE: The purpose of this study was to examine the relationship between
      metabolic and inflammatory markers in patients with diabetic retinopathy (DR).
      METHODS: 208 adult patients with type 2 diabetes participated in this study and
      were categorized into (1) mild nonproliferative diabetic retinopathy (NPDR)
      without clinically significant macular edema (CSME), (2) NPDR with CSME, (3)
      proliferative diabetic retinopathy (PDR) without CSME, and (4) PDR with CSME.
      Variable serum metabolic markers were assessed using immunoassays. Multinomial
      logistic regression analysis was performed. RESULTS: Diabetes duration and
      hypertension are the most significant risk factors for DR. Serum Apo-B and Apo
      B/Apo-A ratio were the most significant metabolic risk factors for PDR and CSME.
      For every 0.1 g/L increase in Apo-B concentration, the risk of PDR and CSME
      increased by about 1.20 times. We also found that 10 pg/mL increase in serum TNF
      alpha was associated with approximately 2-fold risk of PDR/CSME while an increase
      by 100 pg/mL in serum VEGF concentration correlated with CSME. CONCLUSIONS: In
      conclusion, it seems that there is a link between metabolic and inflammatory
      markers. Apo-B/Apo-A ratio should be evaluated as a reliable risk factor for PDR
      and CSME, while the role of increased systemic TNF-alpha and VEGF should be
      explored in CSME.

PMID- 26295058
TI  - Fusion of Heterogeneous Intrusion Detection Systems for Network Attack Detection.
AB  - An intrusion detection system (IDS) helps to identify different types of attacks
      in general, and the detection rate will be higher for some specific category of
      attacks. This paper is designed on the idea that each IDS is efficient in
      detecting a specific type of attack. In proposed Multiple IDS Unit (MIU), there
      are five IDS units, and each IDS follows a unique algorithm to detect attacks.
      The feature selection is done with the help of genetic algorithm. The selected
      features of the input traffic are passed on to the MIU for processing. The
      decision from each IDS is termed as local decision. The fusion unit inside the
      MIU processes all the local decisions with the help of majority voting rule and
      makes the final decision. The proposed system shows a very good improvement in
      detection rate and reduces the false alarm rate. 

PMID- 26295057
TI  - Aspergilli Response to Benzalkonium Chloride and Novel-Synthesized
      Fullerenol/Benzalkonium Chloride Nanocomposite.
AB  - A comprehensive comparative analysis of antifungal potential of benzalkonium
      chloride and newly synthesized fullerenol/benzalkonium chloride nanocomposite was
      conducted to assess the possible impact of carbon-based nanocarrier on
      antimicrobial properties of the commonly used biocide. Physical characterization
      of synthesized nanocomposite showed zeta potential of +37.4 mV and inhomogeneous
      particles size distribution, with nanocomposite particles' dimensions within 30
      143 nm and maximum number of particles at 44 nm. The effect of pure and
      fullerenol nanocarrier-bound biocide was evaluated in eight Aspergillus species.
      In mycelial growth assay, nanocomposite was more potent, as fungicidal effect of
      1.04/0.6 MUg mL(-1) was obtained in all but one of the isolates (A. niger), while
      proportional concentration of pure biocide (0.6 MUg mL(-1)) completely inhibited
      mycelial growth of only three Aspergillus species. However, conidia appear to be
      less susceptible to nanocomposite treatment, as lower fungistatic (MIC) and
      fungicidal (MFC) concentrations were obtained with biocide alone (MIC in range
      from 0.03 to 0.15 MUg mL(-1) and MFC from 0.075 to 0.45 MUg mL(-1)). To a
      different degree, both substances stimulated aflatoxin B1 production and
      inhibited ochratoxin A synthesis. Very low mycelium biomass yield, in range from
      1.0 to 3.0 mg dry weight, was documented in both biocide and nanocomposite
      enriched medium.

PMID- 26295055
TI  - Influence of Melatonin on the Proliferative and Apoptotic Responses of the
      Prostate under Normal and Hyperglycemic Conditions.
AB  - The antitumor properties of melatonin (MLT) are known for prostate cancer cells.
      This study investigated whether MLT affects prostate maturation and interferes
      with tissue injuries induced by diabetes. MLT was administered to Wistar rats
      from 5 weeks of age in the drinking water (10 MUg/kg b.w.), and diabetes was
      induced at the 13th week by streptozotocin (4.5 mg/100g b.w., i.p.). The animals
      were euthanized in the 14th and 21st weeks. MLT reduced the immunostained cells
      for androgen receptor (AR) by 10% in younger rats. Diabetes decreased cell
      proliferation and increased apoptosis. MLT treatment impeded apoptosis (p = 0.02)
      and augmented proliferation (p = 0.0008) and PCNA content in prostate following
      long-term diabetes due to restoration of testosterone levels and expression of
      melatonin receptor type 1B. The effect of MLT (500 uM, 5 mM, and 10 mM) on
      androgen-dependent (22Rv1) and androgen-independent (PC3) cancer cells and human
      prostate epithelial cells (PNTA1) under normal and hyperglycemic conditions (HG,
      450 mg/dL) was analyzed. Contrary to PNTA1 and 22Rv1 cells, MLT improved the
      proliferation of PC3 cells in hyperglycemic medium. The combined data indicated
      that MLT had proliferative and antiapoptotic effects in prostate cells subjected
      to HG levels and it seems to involve specific MLT pathways rather than AR. 

PMID- 26295059
TI  - ASM Based Synthesis of Handwritten Arabic Text Pages.
AB  - Document analysis tasks, as text recognition, word spotting, or segmentation, are
      highly dependent on comprehensive and suitable databases for training and
      validation. However their generation is expensive in sense of labor and time. As
      a matter of fact, there is a lack of such databases, which complicates research
      and development. This is especially true for the case of Arabic handwriting
      recognition, that involves different preprocessing, segmentation, and recognition
      methods, which have individual demands on samples and ground truth. To bypass
      this problem, we present an efficient system that automatically turns Arabic
      Unicode text into synthetic images of handwritten documents and detailed ground
      truth. Active Shape Models (ASMs) based on 28046 online samples were used for
      character synthesis and statistical properties were extracted from the IESK-arDB
      database to simulate baselines and word slant or skew. In the synthesis step ASM
      based representations are composed to words and text pages, smoothed by B-Spline
      interpolation and rendered considering writing speed and pen characteristics.
      Finally, we use the synthetic data to validate a segmentation method. An
      experimental comparison with the IESK-arDB database encourages to train and test
      document analysis related methods on synthetic samples, whenever no sufficient
      natural ground truthed data is available. 

PMID- 26295060
TI  - The Duration of Breastfeeding and Its Association with Metabolic Syndrome among
      Obese Children.
AB  - OBJECTIVE: The objective of this study was to evaluate whether duration of
      breastfeeding is associated with a lower prevalence of metabolic syndrome in
      obese children. METHODS: A retrospective analysis of obese children aged 3 to 18
      years followed at a pediatric outpatient clinic at a single center between the
      years 2008 and 2012. The children were divided according to their breastfeeding
      duration: no breastfeeding, a short period of breastfeeding, and a long term
      breastfeeding. Also, they were divided into metabolic and nonmetabolic syndrome
      groups, based on physical examination and laboratory tests. RESULTS: Out of 4642
      children who visited the clinic, 123 were obese and were included in the study.
      About half of them matched the metabolic syndrome criteria. There was no
      correlation between the prevalence of metabolic syndrome and the duration of
      breastfeeding. Hypertension, abnormal low levels of HDL, high levels of HbA1c,
      and high fasting triglyceride levels were very common in our study population,
      yet no statistical significance was noted among the different breastfeeding
      groups. CONCLUSION: In this study, breastfeeding was not associated with a
      reduced risk for metabolic syndrome, compared with formula feeding, in children
      who are obese.

PMID- 26295061
TI  - Efficacy of Mouthwashes Containing Hydrogen Peroxide on Tooth Whitening.
AB  - The aim of this study was to analyze the efficacy of mouthwashes containing
      hydrogen peroxide compared with 10% carbamide peroxide (CP) gel. Fifty enamel
      dentin samples were obtained from bovine incisors and then stained in a tea
      solution. The stained samples were randomly divided into five groups according to
      the whitening product applied (n = 10): AS: no whitening (negative control), with
      the samples stored in artificial saliva; CR: Crest 3D White mouthwash; LS:
      Listerine Whitening mouthwash; SC: Scope White mouthwash; and OP group: 10% CP
      Opalescence PF (positive control). Color measurements were carried out with a
      spectrophotometer before staining, after staining, and on the 7th, 28th, and 56th
      day of the whitening period. The data were analyzed using two-way analysis of
      variance followed by a Tukey post hoc test. The color change (DeltaE) was
      significantly greater in all the groups compared to that of the AS group. After
      56 days, no significant differences were found among the mouthwash products with
      respect to color change (P > 0.05). The whiteness of the teeth treated with the
      mouthwashes increased significantly over time. Nevertheless, the color change
      achieved with the mouthwashes was significantly lower than that achieved with the
      10% CP at-home bleaching gel. 

PMID- 26295062
TI  - In Vitro and in Vivo Activity of Multitarget Inhibitors against Trypanosoma
      brucei.
AB  - We tested a series of amidine and related compounds against Trypanosoma brucei.
      The most active compound was a biphenyldiamidine that had an EC 50 of 7.7 nM
      against bloodstream-form parasites. There was little toxicity against two human
      cell lines with CC 50 > 100 MUM. There was also good in vivo activity in a mouse
      model of infection with 100% survival at 3 mg/kg i.p. The most potent lead
      blocked replication of kinetoplast DNA (k-DNA), but not nuclear DNA, in the
      parasite. Some compounds also inhibited the enzyme farnesyl diphosphate synthase
      (FPPS), and some were uncouplers of oxidative phosphorylation. We developed a
      computational model for T. brucei cell growth inhibition (R (2) = 0.76) using DNA
      DeltaT m values for inhibitor binding combined with T. brucei FPPS IC 50 values.
      Overall, the results suggest that it may be possible to develop multitarget drug
      leads against T. brucei that act by inhibiting both k-DNA replication and
      isoprenoid biosynthesis. 

PMID- 26295064
TI  - Plasminogen Activator Inhibitor-1, Body Fat and Insulin Action in Aging Women.
AB  - Plasminogen activator inhibitor-1 (PAI-1) over-expression is linked to obesity,
      insulin resistance, and age. We hypothesized that aerobically trained women
      athletes would have reduced PAI-1 regardless of age compared to sedentary
      controls and levels would be associated with hyperinsulinemia. Plasma PAI-1 was
      measured in women athletes who were young (YA, n=19, VO2max=53.7+/-1.1ml/kg/min)
      and older (OA, n=18, VO2max=46.6+/-1.5ml/kg/min) and compared to 19 sedentary
      controls (YC, n=6, VO2max=35.9+/-1.2ml/kg/min; OC, n=13, VO2max=22.1+/
      1.7ml/kg/min). PAI-1 levels did not differ between YA and OA but was 23% higher
      in OC compared to OA (P<0.05). PAI-1 was inversely associated with VO2max,
      directly to %body fat, and subcutaneous abdominal fat, fasting leptin, insulin,
      and first-phase and second-phase insulin response during a hyperglycemic clamp.
      The current results suggest that older athletes have low PAI-1 levels possibly
      due to high levels of physical fitness, reduced body fat, and increased insulin
      action and may contribute to low atherothrombosis and improved cardiovascular
      health.

PMID- 26295063
TI  - Inhibiting macrophage proliferation suppresses atherosclerotic plaque
      inflammation.
AB  - Inflammation drives atherosclerotic plaque progression and rupture, and is a
      compelling therapeutic target. Consequently, attenuating inflammation by reducing
      local macrophage accumulation is an appealing approach. This can potentially be
      accomplished by either blocking blood monocyte recruitment to the plaque or
      increasing macrophage apoptosis and emigration. Because macrophage proliferation
      was recently shown to dominate macrophage accumulation in advanced plaques,
      locally inhibiting macrophage proliferation may reduce plaque inflammation and
      produce long-term therapeutic benefits. To test this hypothesis, we used
      nanoparticle-based delivery of simvastatin to inhibit plaque macrophage
      proliferation in apolipoprotein E deficient mice (Apoe-/- ) with advanced
      atherosclerotic plaques. This resulted in rapid reduction of plaque inflammation
      and favorable phenotype remodeling. We then combined this short-term nanoparticle
      intervention with an eight-week oral statin treatment, and this regimen rapidly
      reduced and continuously suppressed plaque inflammation. Our results demonstrate
      that pharmacologically inhibiting local macrophage proliferation can effectively
      treat inflammation in atherosclerosis.

PMID- 26295065
TI  - Alternative Aging Solutions to Accelerate Resin-Dentin Bond Degradation.
AB  - PURPOSE: This study evaluated the effect of aging solutions on the durability of
      resin-dentin bonds by means of microtensile bond strength (MUTBS) and nanoleakage
      (NL) tests. MATERIALS AND METHODS: The adhesive system Adper Single Bond 2 (3M
      ESPE) was applied according to the manufacturer's instructions to the flattened
      occlusal surface of 40 extracted human molars. After bonding, teeth were
      sectioned to obtain bonded sticks (0.8 mm2 area) which were tested in tension
      immediately or after different storage periods (1 week, 1 month, or 6 months).
      Bonded sticks were kept immersed in 5 different solutions: 1) distilled water
      (DW); 2) 99.9% propionic acid (PA); 3) 99% acetic acid (AA); 4) 75% ethanol (ET),
      and 5) mineral oil (MO). To determine NL, bonded sticks from each experimental
      condition were immersed in silver nitrate and analyzed by SEM. Data were analyzed
      by two-way repeated measure ANOVA and Tukey's test (alpha=0.05). RESULTS: Faster
      degradation of bond strength (1 week) could be seen for AA and ET (p<0.05) in
      comparison with DW. Specimens stored in PA and DW showed bond strengths
      significantly reduced after one and six months, respectively (p<0.05). No
      degradation of the resin-dentin bond strengths was observed for specimens stored
      in MO (p>0.05). Nanoleakage increased for all groups except MO after storage.
      CONCLUSION: Propionic acid, acetic acid, and ethanol can be used as alternative
      aging solutions to more quickly obtain results on the bond resistance to
      degradation.

PMID- 26295066
TI  - Effect of Hydrofluoric Acid Concentration on Resin Adhesion to a Feldspathic
      Ceramic.
AB  - PURPOSE: To evaluate the effect of different concentrations of hydrofluoric acid
      (HF) on the contact angle and the resin bond strength durability to feldspathic
      ceramic. MATERIALS AND METHODS: To evaluate the contact angles of distilled water
      on etched feldspathic ceramic, 25 specimens (12*10*2.4 mm) of VitaBlocks Mark II
      were used, divided into 5 groups (n=5): one unconditioned control (UC) group with
      no ceramic surface treatment, and 4 other groups that were etched for 60 s with
      different concentrations of HF: 1% (HF1), 3% (HF3), 5% (HF5) and 10% (HF10). The
      bond testing utilized 40 ceramic blocks (12*10*4 mm) that were fabricated and
      subjected to the same surface treatments as previously mentioned (excluding the
      control). The etched surfaces were silanized and resin cement was applied. After
      24 h, the blocks were sectioned to produce bar specimens that were divided into
      two groups, non-aged (immediate testing) and aged (storage for 230 days+12,000
      thermocycles at 5 degrees C and 55 degrees C), and subjected to microtensile
      testing (MUTBS). Micromorphogical analysis of the treated surfaces was also
      performed (atomic force and scanning electron microscopy). One-way ANOVA and
      Tukey's tests were applied for data analysis. RESULTS: UC had the highest contact
      angle (61.4 degrees ), whereas HF10 showed the lowest contact angle (17.5 degrees
      ). In non-aged conditions, different acids promoted statistically similar bond
      strengths (14.2 to 15.7 MPa) (p>0.05); in terms of bond durability, only the bond
      strength of the HF1 group presented a statistically significant decrease
      comparing before and after aging (14.5 to 10.2 MPa). CONCLUSION: When etched with
      3%, 5%, or 10% hydrofluoric acid, the ceramic tested showed stable resin adhesion
      after long-term aging.

PMID- 26295067
TI  - Effect of Adhesive Resin Type for Bonding to Zirconia Using Two Surface
      Pretreatments.
AB  - PURPOSE: This laboratory study evaluated the short-term adhesive properties of
      one 10-MDP-containing and two MDP-free resin composite cements, using two types
      of zirconia surface pretreatments. MATERIALS AND METHODS: Eighteen sintered
      zirconia disks (Procera, Nobel Biocare) were randomly divided into three study
      groups according to their surface treatment: (a) polished surface (control
      group); (b) airborne-particle abraded (grit blasted) with 50-MUm aluminum
      trioxide (APA); and (c) selective infiltration etching (SIE). The zirconia disks
      were then bonded to 180 pre-aged composite resin disks (0.9 mm*0.7 mm) using
      three different resin composite cements (Panavia F2.0, Esthetic, and Aegis).
      Resin-zirconia adhesion strength was evaluated using the microshear bond strength
      test (MUSBS) after 24 h (baseline) and 2 weeks of storage in deionized water at
      37 degrees C. Three-way ANOVA, one-way ANOVA, and Scheffe's post-hoc tests were
      used to analyze the data (p=0.05). RESULTS: Surface treatments significantly
      influenced the MUSBS (p<0.001). The highest mean MUSBS values were recorded with
      the MDP-containing resin composite cement (Panavia F2.0) in both SIE (32.4+/-5.3
      MPa) and APA (28.6+/-8.8 MPa) groups. Water storage significantly reduced the
      bond strength obtained with the MDP-free cements (Esthetic and Aegis) and in the
      control group, while the bond strength in SIE and APA groups using the 10- MDP
      containing resin composite cement exhibited relatively unchanged values.
      CONCLUSION: SIE and APA in combination with the 10-MDP-containing resin composite
      cement established a strong, durable bond to zirconia substrates under short-term
      aging conditions. The cement containing amorphous calcium phosphate (Aegis) did
      not bond to zirconia surfaces. During the observation period, MUSBS decreased
      significantly due to hydrolytic degradation, except when the 10-MDP-containing
      resin composite cement (Panavia F2.0) was used in the SIE and APA groups.

PMID- 26295069
TI  - A hydrogen bonded molecular capsule versus a 3D network of tripodal
      organopolysilanols.
AB  - 1,3,5-Triethylbenzene based tripodal trisilanols were synthesized. The X-ray
      crystal structures of trisilanols showed capsule formation as well as non
      capsular network formation using silanol hydrogen bonds. The (1)H NMR and ESI
      mass spectroscopy experiments for solution state binding supported encapsulation
      of the halide ions in the cavity of the molecular capsule with a C3 symmetry. 

PMID- 26295068
TI  - Effect of Matrix Metalloproteinase-inhibiting Solutions and Aging Methods on
      Dentin Bond Strength.
AB  - PURPOSE: This study examined the effects of matrix metalloproteinase-inhibiting
      solutions and aging methods on the bond strength between resin composite and
      human dentin. MATERIALS AND METHODS: Crown segments of 105 human non-carious
      molars were bonded using simulated pulpal pressure at 20 cm water pressure. The
      teeth were randomly split into 5 groups according to the solution applied: CG
      (control, no solution), CHX (0.2% chlorhexidine), EPE (10% ethanolic propolis
      extract), APE (aqueous propolis extract), and E (70% ethanol). Each solution was
      left on the acid-etched dentin for 1 min. Adper Single Bond 2 and resin composite
      (Filtek Z350 XT) were applied to all specimens. The 5 groups were subdivided
      according to the aging method: SI (sectioned immediately); S (storage in
      artificial saliva for 6 months); and T (thermomechanical aging with 240,000
      mechanical cycles and 1000 thermal cycles). Specimens were sectioned into sticks
      and subjected to microtensile testing. Bond strength data were analyzed by two
      factor ANOVA followed by a post-hoc Tukey's test (alpha=0.05). RESULTS: For the
      factor "solution", there was no significant difference among the groups (p=0.32).
      For the factor "aging method", significant differences were found (p<0.001), with
      the following mean bond strengths (MPa): SI: 31.1; S: 24.4; T: 26.8. CONCLUSIONS:
      The use of matrix metalloproteinase-inhibiting solutions on dentin as an adjunct
      to the application of an etch-and-rinse adhesive does not prevent the loss of
      bond strength after aging. Nevertheless, these solutions have no adverse effect
      on adhesion to tooth structure.

PMID- 26295070
TI  - Thienyl-BOPHY dyes as promising templates for bulk heterojunction solar cells.
AB  - The synthesis and characterization of bis(difluoroboryl)-1,2-bis((1H-pyrrol-2
      yl)methylene)hydrazone functionalized with two lateral vinyl-thienyl modules and
      exhibiting strong absorption in the 400-800 nm window in thin films are reported.
      Bulk heterojunction solar cells assembled with these dyes and a fullerene
      derivative (PC71BM), using very small quantities of the additive diiodooctane,
      give a power conversion efficiency as high as 4.3% with short-circuit current
      values of 10.9 mA cm(-2), an open-circuit voltage of 0.7 V and external quantum
      efficiencies higher than 70% over a broad range of wavelengths (580 to 720 nm). 

PMID- 26295071
TI  - Wide gamut white light emitting diodes using quantum dot-silicone film protected
      by an atomic layer deposited TiO2 barrier.
AB  - Wide gamut light emitting diodes using quantum dot-silicone film protected by
      atomic layer deposited TiO2 film were demonstrated. The core/shell QDs with multi
      emission peaks were synthesised by a one-pot approach, in which the emission
      wavelength and colour composition were in situ adjusted during the synthetic
      process. 

PMID- 26295073
TI  - A turn-on fluorescent probe for tumor hypoxia imaging in living cells.
AB  - A novel "turn-on" fluorescent probe HP for hypoxia imaging was designed and
      synthesized based on rhodamine B and a naphthalimide fluorophore. The
      fluorescence of HP is very weak owing to the FRET effect from rhodamine B to the
      azo-naphthalimide unit. Under hypoxia conditions, the azo-bond is reduced and the
      fluorescence at 581 nm enhances dramatically as a result of disintegration of the
      quencher structure. Verified by the cyclic voltammetry reduction potential and
      proposed product HPN, the probe HP could undergo the chemical and cytochrome P450
      enzymatic reduction quickly. When cultured with HeLa cells, HP showed remarkable
      fluorescence differences at various oxygen concentrations, and the ratio of
      fluorescence intensity between hypoxic and normoxic cells could reach 9 fold. 

PMID- 26295072
TI  - Synthesis of double-clickable functionalised graphene oxide for biological
      applications.
AB  - Azide- and alkyne-double functionalised graphene oxide (Click(2) GO) was
      synthesised and characterised with attenuated total reflectance Fourier transform
      infrared spectroscopy (ATR-FTIR), thermogravimetric analysis (TGA) and Raman
      spectroscopy. Fourteen-percentage increase in azide content was found, after pre
      treatment of GO with meta-chloroperoxybenzoic acid (mCPBA), determined with
      elemental analysis. No effect on A549 cell viability was found, up to 100 MUg mL(
      1) and 72 h of incubation, determined with the modified lactate dehydrogenase
      (mLDH) assay. Two sequential copper(i) catalysed azide-alkyne cycloaddition
      (CuAAC) reactions were performed to conjugate the propargyl-modified blood-brain
      barrier targeting peptide Angiopep-2, and a bis-azide polyethylene glycol (MW =
      3500), to the Click(2) GO. The final conjugate was characterised with ATR-FTIR
      and TGA. 

PMID- 26295074
TI  - A ternary hybrid of carbon nanotubes/graphitic carbon nitride nanosheets/gold
      nanoparticles used as robust substrate electrodes in enzyme biofuel cells.
AB  - A novel ternary hybrid of carbon nanotubes/graphitic carbon nitride
      nanosheets/gold nanoparticles was prepared and used as robust substrate
      electrodes for fabricating membrane-less glucose/O2 enzyme biofuel cells (EBFCs),
      and a remarkably improved power output was observed for the prepared EBFC. 

PMID- 26295075
TI  - Highly sensitive "signal-on" electrochemiluminescent biosensor for the detection
      of DNA based on dual quenching and strand displacement reaction.
AB  - A "signal-on" electrochemiluminescent DNA biosensing platform was proposed based
      on the dual quenching and strand displacement reaction. This novel "signal-on"
      detection strategy revealed its sensitivity in achieving a detection limit of 2.4
      aM and its selectivity in distinguishing single nucleotide polymorphism of target
      DNA. 

PMID- 26295076
TI  - Fabrication of functionalized polysulfide reservoirs from large graphene sheets
      to improve the electrochemical performance of lithium-sulfur batteries.
AB  - The effect of graphene lateral size on the electrochemical performance of lithium
      sulfur (Li-S) batteries is often ignored. In this study, the thermally exfoliated
      large lateral-sized graphene (denoted LTG) was employed as the conductive matrix
      to support sulfur, and its performance was then compared with that of a smaller
      lateral-sized graphene (denoted STG) for Li-S batteries. The results showed that
      the LTG-S composite exhibited much higher capacity retention (53%) versus the STG
      S (29%) and better rate capabilities. Because they were both identical in
      morphology, in terms of sulfur content and sulfur distribution, the improved
      properties probably resulted from the potential prevention of polysulfide
      diffusion upon cycling due to the larger graphene-based network and higher aspect
      ratio of the LTG matrix, referred as better polysulfide reservoirs. To further
      improve the cell performance, a reduced graphene oxide-coated carbon fiber paper
      (RCF) was inserted between the LTG-S cathode and the separator by a simple drop
      coat method, which provided an increased conductive surface area for polysulfides
      to be oxidized/reduced and buffered volume expansion. As expected, the discharge
      capacities of 1143 and 622 mA h g(-1) at first use and after 100th cycles were
      obtained with an average Coulombic efficiency of 99.7%, which were higher than
      847 and 455 mA h g(-1) for the cathode without the RCF, respectively. This study
      highlights the significance of large graphene sheets and interlayers on the
      inhibition of polysulfide diffusion and offers a new way to solve the problems of
      Li-S batteries. 

PMID- 26295077
TI  - Health and happiness is more important than weight': a qualitative investigation
      of the views of parents receiving written feedback on their child's weight as
      part of the National Child Measurement Programme.
AB  - BACKGROUND: The present study aimed to explore parental perceptions of overweight
      children and associated health risks after receiving National Child Measurement
      Programme (NCMP) weight feedback. METHODS: Fifty-two parents of overweight and
      obese children aged 4-5 years and 10-11 years enrolled in the NCMP programme in
      England in 2010-2011 participated in qualitative, semi-structured interviews
      about their perceptions of their child's weight and health risk after receiving
      weight feedback. Interviews were audio tape recorded and were conducted either by
      telephone (n = 9) or in the respondents' homes (n = 41). Interviews were
      transcribed verbatim and analysed using interpretative thematic analysis.
      RESULTS: Parents who received NCMP written feedback informing them that their
      child was overweight disregarded the results because they viewed 'health and
      happiness as being more important than weight'. The feedback was viewed as less
      credible because it did not consider the individual child's lifestyle.'Broad
      definitions of healthy' were described that did not include weight,such as
      reference to the child having good emotional and physical health and a healthy
      diet. Parents attributed weight to 'inherited/acquired factors' such as genetics
      or puppy fat, or did not regard their child's 'appearance' as reflecting being
      overweight. 'Cultural influence' also meant that being overweight was not viewed
      negatively by some non-white parents. CONCLUSIONS: After receiving written weight
      feedback, parents use methods other than actual weight when evaluating their
      child's weight status and health risks. Parents' conceptions of health and weight
      should be considered when communicating with parents, with the aim of bridging
      the gap between parental recognition of being overweight and subsequent behaviour
      change.

PMID- 26295078
TI  - PCSK9 Inhibitors and Cardiovascular Events.

PMID- 26295079
TI  - Global economic impact of diabetes.

PMID- 26295080
TI  - Medical management of peripheral artery disease in diabetes mellitus.

PMID- 26295081
TI  - Coronary revascularization in diabetic patients.

PMID- 26295082
TI  - Dipeptidyl peptidase-4 inhibitors and  cardiovascular outcomes: decongesting  the
      matter.

PMID- 26295083
TI  - Blood sugar levels in heart failure patients predict  risk of early death,
      hospitalizations, and diabetes.

PMID- 26295085
TI  - Letter to the editor regarding Disciglio et al.: interstitial 22q13 deletions not
      involving SHANK3 gene: a new contiguous gene syndrome.

PMID- 26295084
TI  - The cannabis experiment.

PMID- 26295086
TI  - Patient Safety in Nephrology Nurse Practice Settings.

PMID- 26295087
TI  - Facilitating Safety through Patient Engagement.

PMID- 26295088
TI  - Patient Safety and Patient Safety Culture: Foundations of Excellent Health Care
      Delivery.
AB  - In 1999, patient safety moved to the forefront of health care based upon
      astonishing statistics and a landmark report released by the Institute of
      Medicine (IOM). This repor4 To Err is Human: Building a Safer Health System,
      caught the attention of the media, and there were headlines across the nation
      about the safety (or lack of safety)for patients in healthcare organizations. In
      the ensuing years, there have been many efforts to reduce medical errors.
      Clinicians reviewed their practices, researchers lookedfor better ways of doing
      things, and safety and quality organizationsfocused attention on the topic of
      patient safety. Initiatives and guidelines were established to define, measure,
      and improve patient safety practices and culture. Nurses remain central to
      providing an environment and culture of safety, and as a result, nurses are
      emerging as safety leaders in the healthcare setting. This article discusses the
      history of the patient safety movement in the United States and describes the
      concepts of patient safety and patient safety culture as the foundations for
      excellent health care delivery.

PMID- 26295089
TI  - Patient Safety Culture in Nephrology Nurse Practice Settings: Initial Findings.
AB  - Patient safety culture has been studied in many practice settings, but there is a
      dearth of information on the culture of safety in nephrology nurse practice
      settings. This research study employed the use of an online survey to assess
      patient safety cultures in nephrology nurse practice settings. The survey was
      created using items from two Agency for Healthcare Research and Quality (AHRQ)
      survey assessment tools--the Hospital Survey on Patient Safety Culture and the
      Medical Office Survey on Patient Safety Culture. Select items from these tools
      were combined to address the safety of care delivered in hospital and outpatient
      nephrology nurse practice settings. Almost 1,000 nephrology nurses responded to
      the survey. Analysis of results and comparison with AHRQ comparative data found
      high ratings for teamwork, but indicted a continued needfor additional education
      and attention related to hand hygiene, medication administration safety,
      communication, and prioritization in nephrology practice settings. Nurses in all
      nephrology nurse practice settings need to routinely assess and positively
      contribute to the culture of patient safety in their practice settings, and lead
      and engage in efforts to ensure that patients are safe.

PMID- 26295090
TI  - Exploring Death Anxiety and Burnout Among Staff Members Who Work In Outpatient
      Hemodialysis Units.
AB  - Outpatient hemodialysis unit staff members are at risk for psychological stress,
      including death anxiety, unresolved grieving, and burnout, due tofrequent
      interactions with chronically ill patients who have a high mortality rate.
      Experiencing death anxiety and burnout may impair the ability to build
      interpersonal relationships, decrease job satisfaction, and impact quality of
      patient care. A quantitative study to evaluate the effect of educational classes
      on the level of death anxiety and burnout among hemodialysis caregivers revealed
      a decrease in participants' level of death anxiety and a decrease in emotional
      exhaustion in one area that was directly related to the work environment
      Information from the study can be used to decrease psychological stress through
      education and support for staff members who work in the hemodialysis unit
      environment.

PMID- 26295091
TI  - Attitude and Empowerment as Predictors Of Self-Reported Self-Care and A1C Values
      among African Americans With Diabetes Mellitus.
AB  - Diabetes mellitus is a leading cause of end stage renal disease among African
      Americans. The complications associated with diabetes can largely be reduced with
      effective diabetes self-management. Selected variables were tested as predictors
      of self-reported self-care, and self-reported self-care was tested as a predictor
      of A1C among 100 African-American individuals with diabetes. Participants scored
      high on their understanding of diabetes, its treatment, and engagement in self
      care activities, but this was not reflected in their body mass index levels or A
      IC values.

PMID- 26295092
TI  - Application of Dorothea Orem's Theory of Self-Care to the Elderly Patient on
      Peritoneal Dialysis.
AB  - Due to improvements in health care and increasing life expectancy, a greater
      number of elderly patients need renal replacement therapy. Dorothea Orem's Theory
      of Self-Care is an appropriate model to guide healthcare providers addressing the
      unique capabilities of this generation. The utilization and promotion of
      peritoneal dialysis as a therapy option offers the elderly an improved quality of
      life with a greater sense of self-worth. Literature has shown the elderly have
      superior technique and similar peritonitis-free survival rates as the younger
      population.

PMID- 26295093
TI  - Blood Glucose Levels of Patients With Diabetes in the Immediate Post-Acute
      Hemodialysis Period: An Exploratory Study.
AB  - PROBLEM/PURPOSE: To establish the evidence on which to base a protocol for
      monitoring capillary blood glucose in hospitalized patients with diabetes
      mellitus in the immediate post-acute hemodialysis period. SAMPLE: Hospitalized,
      non-critically ill, adult patients (n = 68) with diabetes undergoing acute
      hemodialysis treatments. METHODS: Capillary blood glucose was tested 30 minutes
      prior to the end of the hemodialysis treatment, at the end of the treatment, and
      30 minutes and 60 minutes post-treatment. Data were analyzed to determine both
      within and between patient variability. RESULTS: Glucose levels varied widely
      before, during, and after hemodialysis, with greatest variability at 60 minutes
      post-hemodialysis. Levels did not vary based on diabetes type or admitting
      diagnosis. Possible relationships were identified with length of treatment,
      insulin administration prior to treatment, and food consumed within an hour after
      treatment. CONCLUSIONS/NURSING IMPLICATIONS: Testing post-dialysis glucose levels
      earlier than 60 minutes post-treatment may miss the need for additional
      medication.

PMID- 26295094
TI  - An Ethical Approach to Renal Replacement Decisions in the Elderly.
AB  - Moral concerns and distress can surround the decision to initiate, withhold, or
      withdraw renal replacement therapy (RRT) in those ages 65 and older with multiple
      co-morbidities. The nurse's moral responsibility of caring is often overlooked
      when healthcare decisions are made regarding RRT. One remedy is shared decision
      making in which the nurse acts as patient advocate. This article discusses two
      guidelinesfor shared decision making that have been used successfully and
      presents a case study on shared decision making regarding withholding or
      withdrawing RRT

PMID- 26295095
TI  - Educating Older Adults with Chronic Kidney Disease.

PMID- 26295096
TI  - Review of Atlanticus Scudder, 1894 (Orthoptera: Tettigoniidae: Tettigoniinae)
      from China, with description of 27 new species.
AB  - Atlanticus Scudder illustrates a disjunctive distribution comprising 1 subgenus
      and 10 valid species from eastern North America and 2 subgenera and 14 valid
      species from eastern Asia. Several authors also predicted that it would appear
      that China was rich in new species of the genus Atlanticus. Based on
      investigation of male stridulatory apparatus, as well as previously used
      characters, including male and female abdominal apex and measurements of various
      structures, we present a taxonomic account of 43 species of Atlanticus from
      China. Twenty-seven species of Atlanticus new to science are described. Erroneous
      synonyms are noted, based on examination of topotypes. Atlanticus changi Tinkham,
      1941 and Atlanticus pieli Tinkham, 1941 are valid species and not synonyms of
      Atlanticus kiangsu Ramme, 1939. Atlanticus jeholensis Mori, 1935 is also valid
      and not a synonym of Atlanticus sinensis Uvarov, 1924. Moreover, the supposedly
      important character, i.e., length comparison between male pronotum and tegmen, is
      not suitable for differentiating two subgenera of Atlanticus, because it is easy
      to cause confusion. In contrast, the architecture of the male tegmen is a useful
      character to differentiate the two subgenera. The previous mentioned Species
      Groups and the corresponding descriptions are also studied. Necessary
      illustrations are provided.

PMID- 26295097
TI  - A new tuberculated Pristimantis (Anura, Terrarana, Strabomantidae) from the
      Venezuelan Andes, redescription of Pristimantis pleurostriatus, and variation
      within Pristimantis vanadisae.
AB  - A new tuberculated Pristimantis is described from the eastern versant of the
      Venezuelan Andes. The new species is found in cloud forest at around 1600 masl on
      the eastern side of the Cordillera de Merida. It is distinguished from other
      similar tuberculated species by its round, ill-defined canthus rostralis, ill
      defined canthal stripe, and absence of pale spots on the groin and posterior
      surface of thighs. Pristimantis pleurostriatus is a poorly known species found in
      cloud forest on the western slopes of the Venezuelan Andes. We redescribe the
      species based on topotypic specimens. Pristimantis vanadisae is a polychomatic
      species varying dramatically in pattern; four chromotypes are described.
      Molecular data are presented which distinguish among tuberculated and other
      species of Pristimantis in the Cordillera de Merida. Molecular data also support
      placement of Mucubatrachus and Paramophrynella in Pristimantis.

PMID- 26295098
TI  - Apostenus ducati (Araneae: Liocranidae) sp. nov.: a second Nearctic species in
      the genus.
AB  - Apostenus ducati sp. nov. is described from montane areas in or adjacent to the
      Columbia River basin of southeastern British Columbia in Canada and northern
      Washington and northwestern Montana in the United States. This is the second
      Nearctic species of this primarily Palaearctic genus. Unlike most liocranids, A.
      ducati apparently is restricted to open rocky habitats, such as talus and scree
      slopes, and on mountain peaks. Throughout most of its range, specimens occur in
      low numbers and populations are patchily distributed. Also, populations appear to
      be concentrated in the upper regions of the Flathead River watershed in British
      Columbia, an area of significant and competing ecological and economic values.
      Because of these factors, A. ducati is potentially a species of conservation
      concern.

PMID- 26295099
TI  - The amathiiform Ctenostomata (phylum Bryozoa) of New Zealand--including four new
      species, two of them of probable alien origin.
AB  - The status of the vesiculariid ctenostome genus Amathia in New Zealand has been
      evaluated on the basis of all known material, including historic specimens in
      museums and those newly collected during formal surveillance of ports, harbours
      and vessels for possible alien species. Eight species are recognised, four of
      them new to science. Amathia gracei n. sp. and Amathia zealandica n. sp. are the
      only apparently endemic species. Amathia chimonidesi n. sp. appears to be a
      previously unrecognised alien species and is known only from shipping harbours
      and/or yacht marinas and some nearby beaches. Amathia similis n. sp. has been
      known in the Auckland area since the 1960s but was confused with A. distans Busk.
      Amathia bicornis (Tenison-Woods), A. biseriata Krauss, A. lamourouxi Chimonides
      and A. wilsoni Kirkpatrick are Australasian species that occur naturally on both
      sides of the Tasman Sea. Of this latter group, A. bicornis was discovered only at
      a single locality on the southwest coast of North Island in 1983 on a fucoid
      seaweed and it may be relatively re-cently self-introduced. A specimen of A.
      lendigera (Linnaeus) in the Museum of New Zealand, purportedly from Napier, is
      considered to be based on a misunderstanding or a labelling error and does not
      represent a failed alien introduction. The Amathia-like vesiculariid Bowerbankia
      citrina (Hincks) sensu lato is newly recorded for New Zealand. Keys are provided
      to the amathiiform (i.e. Amathia and Amathia-like) Ctenostomata of New Zealand
      and to the worldwide species of Amathia and Bowerbankia with zooid clusters
      spiralled on stoloniform axes.

PMID- 26295100
TI  - A new genus of the subfamily Metrodorinae (Orthoptera: Tetrigidae) from Vietnam.
AB  - The monotypic genus Cleostratoides gen. nov. (type species Cleostratoides
      exoticus sp. nov. from Vietnam) is described in the subfamily Metrodorinae. New
      genus is closely related to the genera Mazarredia Bolivar, 1887, Xistrella
      Bolivar, 1909, Pseudoxistrella Liang, 1991, Orthotettixoides Zheng, 1998 and
      Bermania Storozhenko, 2012, but easily distinguished from all of them by the
      lateral ocelli situated just under fastigium of vertex and by the antennal
      sockets placed distinctly above the lower margin of eyes.

PMID- 26295101
TI  - Descriptions of five new species of Metriaclima (Teleostei: Cichlidae) from Lake
      Malawi, Africa.
AB  - Lake Malawi is known for its endemic haplochromine species flock, most notably
      the rock-dwelling cichlids known as mbuna. One of the larger genera of mbuna is
      Metriaclima, a group consisting of 31 described species (including the five
      described herein) and approximately 45 recognized unique populations. Metriaclima
      is diagnosed by its feeding behavior and several morphological characteristics
      including the angle of the vomer and the presence of bicuspid teeth in the outer
      row of both the upper and lower jaws. Metriaclima zebra, the type species for the
      genus, was described based on a single specimen. While the collection location of
      this holotype is not known, based on the travel records of its collector, it is
      likely that the specimen originated from Likoma Island. The holotype was
      therefore compared to specimens from several localities around this island and
      was found to be morphologically indistinguishable from some of these. This study
      includes the morphological analysis of 496 specimens of Metriaclima belonging to
      31 collections from Lake Malawi. Morphometric differences were analyzed and the
      relationships among several distinguishable populations of Metriaclima zebra were
      investigated. Our study further resulted in the description of the following five
      new species belonging to the M. zebra species complex: M. pambazuko, M.
      lundoense, M. midomo, M. tarakiki, and M. nigrodorsalis. These species were
      distinguished and described based on color patterns, morphometric, meristic, and
      ecological differences. These new species were compared with and distinguished
      from nearby populations of Metriaclima having similar pigmentation patterns
      and/or similar ecological niches. An artificial dichotomous key to the described
      species of Metriaclima is presented.

PMID- 26295102
TI  - Ampharetidae (Annelida: Polychaeta) from Japan. Part II: Genera with elevated and
      modified notopodia.
AB  - The second paper of the series about Ampharetidae from Japan includes twelve
      species of four genera with elevated and modified notopodia, Anobothrus Levinsen,
      1884, Sosane Malmgren, 1866 (including species of the synonymized genera
      Muggoides Hartman, 1965, Sosanopsis Hessle, 1917, and Genus A sensu Uebelacker
      1984), Tanseimaruana gen. nov., and Zatsepinia Jirkov, 1986. Tanseimaruana gen.
      nov. is related to Amphicteis Grube, 1850, but lacks prostomial glandular ridges
      and has a velum-like dermal outgrowth with two pairs of lobes across the dorsum
      of the first abdominal unciniger. The new genus comprises Tanseimaruana vestis
      comb. nov. (Hartman, 1965) (formerly Amphicteis vestis) and T. boninensis sp.
      nov. Seven additional new species, Anobothrus dayi sp. nov., A. fimbriatus sp.
      nov., A. flabelligerulus sp. nov., Sosane brevibranchiata sp. nov., Sosane
      trigintaduo sp. nov., S. uebelackerae sp. nov. (formerly Genus A sensu
      Uebelacker), and Zatsepinia jirkovi sp. nov., are described. Sosane cf. cinctus
      (Hartman, 1965), Sosane wireni (Hessle, 1917), and Zatsepinia rittichae Jirkov,
      1986, all species previously known from the North Atlantic, are recorded from the
      North Pacific for the first time. A phylogenetic analysis of Sosane (including
      the synonymized genera Mugga Eliason, 1955, Muggoides, Sosanopsis, and Genus A
      sensu Uebelacker) suggests monophyly of the genus with Lysippe Malmgren, 1866 as
      sister taxon, and a monophyletic clade [Sosane cinctus, Sosane uebelackerae sp.
      nov., Mugga spp.] within Sosane. The monotypic genus Melinnata Hartman, 1965 has
      been found indeterminable.

PMID- 26295103
TI  - Two new fish species of the subfamily Anthiinae (Perciformes, Serranidae) from
      the Marquesas.
AB  - Two new species of anthiine fishes are described from the Marquesas Islands,
      French Polynesia. Plectranthias flammeus was found at depths from 20-45 m and is
      characterized by dorsal rays X, 14 or 15, with spines 1-6 bearing fleshy white
      tabs at their tips, longest fleshy tab on spine 4; 14 unbranched pectoral rays;
      lateral line incomplete with 16-17 tubed scales; preopercle with 8-10 small
      spines along posterior margin and 2 antrorse spines on ventral margin; broad,
      fiery red-orange streak across lower cheek; head and body with irregularly spaced
      maroon-ringed yellow blotches on a white background; pair of small dark oblong
      spots (red with black centers in life) on the bases of the middle rays of the
      caudal fin. Pseudanthias oumati was found on the outer reef slope of Fatu Hiva at
      a depth of 50-55 m and is characterized by 3rd dorsal spine elongate and tipped
      with fleshy yellow filament extending beyond tip of spine; lateral-line scales
      43; gill rakers 10 + 28; no papillae on posterior edge of orbit; front of upper
      lip not thickened (male condition unknown); caudal fin lunate; color of female
      yellow, all fins yellow with narrow magenta margin (except pectoral fin, which
      lacks magenta); no stripe from snout to pectoral base; small scales located on
      basal quarter of soft-dorsal fin from segmented rays 1-12; dorsal profile of head
      slightly concave.

PMID- 26295104
TI  - New species and new distribution records in Rhinotragini (Coleoptera:
      Cerambycidae: Cerambycinae).
AB  - The tribe Rhinotragini is a highly diverse assemblage of species; several of the
      genera that currently have a large number of species assigned to them are
      polyphyletic in nature and are in need of additional study and revisionary work.
      Because of this need for revisionary work, it is not currently possible to
      construct meaningful keys for the existing species or the ones described in the
      following pages. In 2010, Martins & Santos-Silva studied the large genus Ommata
      White, 1855, and elevated subgenera to generic rank, including assigning several
      species to the genus Eclipta Bates, 1873. Further study of that group
      necessitates the description of two new species from Central America. Odontocera
      Audinet-Serville, 1833 is a larger genus with 83 species from Central and South
      America currently assigned to it. To make the names available for a current
      revisionary study in progress, three new species from Costa Rica and Ecuador are
      described below. Study of material in the MZSP provided several new country and
      state records for various rhinotragine species. The work is divided in two parts:
      descriptions of new species, new records, and correction of geographical
      distribution by Martins, Bezark, and Santos-Silva; and a report of the first host
      plant records for Eclipta lucida sp. nov. by Berkov. The latter section also
      describes mtDNA sequence data (COI) used to evaluate the possibility that
      polymorphic females of E. lucida represent cryptic species.

PMID- 26295105
TI  - Description of a new species and record of Bactrocera Macquart
      (Diptera,Tephritidae) from China.
AB  - One new species, Bactrocera (Zeugodacus) anala Chen et Zhou, sp.nov, and one
      newly recorded species, B. (Z.) armillata (Hering, 1938), from China are
      described and illustrated. The male of B. (Z.) armillata (Hering) was discovered
      for the first time and as a result the species is moved from subgenus Bactrocera
      to subgenus Zeugodacus. In addition, the morphological differences and comparing
      illustrations of B. (Z.) adusta (Wang et Zhao) and B. (Z.) biguttata (Bezzi), are
      provided.

PMID- 26295106
TI  - Molecular phylogenetics of ponerine ants (Hymenoptera: Formicidae: Ponerinae).
AB  - Recent molecular phylogenetic studies of ants (Hymenoptera: Formicidae) have
      revolutionized our understanding of how these ecologically dominant organisms
      diversified, but detailed phylogenies are lacking for most major ant subfamilies.
      I report the results of the first detailed phylogenetic study of the ant
      subfamily Ponerinae, a diverse cosmopolitan lineage whose properties make it an
      attractive model system for investigating social and ecological evolution in
      ants. Molecular sequence data were obtained from four nuclear genes (wingless,
      long-wavelength rhodopsin, rudimentary [CAD], 28S rDNA; total of ~3.3 kb) for 86
      ponerine taxa, representing all three ponerine tribes, 22 of the 28 currently
      recognized genera, and 14 of the 18 informal subgenera of Pachycondyla, a
      heterogeneous grouping whose monophyly is doubtful on morphological grounds.
      Phylogenetic reconstructions using maximum likelihood and Bayesian inference
      support the monophyly of Ponerinae and tribe Platythyreini, but fail to support
      the monophyly of the large tribe Ponerini due to its inclusion of the unusual
      genus Thaumatomyrmex. Pachycondyla is inferred to be broadly non-monophyletic.
      Numerous novel generic and suprageneric relationships are inferred within
      Ponerini, which was found to consist of four major multi-generic clades (the
      Ponera, Pachycondyla, Plectroctena and Odontomachus genus groups) plus the single
      genera Hypoponera and Harpegnathos. Uncertainty remains in some regions of the
      phylogeny, including at the base of Ponerini, possibly reflecting rapid
      radiation. Divergence dating using a Bayesian relaxed clock method estimates an
      origin for stem Ponerinae in the upper Cretaceous, a major burst of
      diversification near the K/T boundary, and a rich and continual history of
      diversification during the Cenozoic. These results fail to support the
      predictions of the "dynastic-succession hypothesis" previously developed to
      explain the high species diversity of Ponerinae. Though model-based
      reconstructions of historical biogeography and trait evolution were not attempted
      in this study, the phylogeny suggests that ponerine evolution was marked by
      regionalized radiations and frequent faunal exchange between major biogeographic
      provinces. The reported results also imply multiple origins of cryptobiotic
      foraging, mass raiding behavior, and gamergate reproduction within Ponerinae,
      highlighting the value of the subfamily as a model for studying the incipient
      evolution of these and other ecological and behavioral traits.

PMID- 26295107
TI  - Species of Bicellaria Macquart (Diptera: Hybotidae) of Europe, with descriptions
      of four new species.
AB  - Species of the genus Bicellaria (Diptera: Hybotidae) of Europe are reviewed.
      Altogether four new species are describes, viz B. andorra sp. nov. (Andorra,
      France), B. italica sp. nov. (Europe), B. kocoureki sp. nov. (Bulgaria), and B.
      setipalpus sp. nov. (Italy). Bicellaria dispar Oldenberg, 1920 is redescribed and
      lectotype is designated. Bicellaria bisetosa Tuomikoski, 1936 is newly
      synonymized with B. uvens Melander, 1928. Illustrations of male terminalia and a
      key to all known European species are provided.

PMID- 26295108
TI  - The centipede fauna (Chilopoda) of the island of Cyprus, with one new
      lithobiomorph species.
AB  - The centipede (Chilopoda) fauna of Cyprus, which was almost unknown, has been
      analysed by examining more than 1,800 specimens sampled from 185 sites, besides
      revising critically the few published data. A total of 26 species are listed and
      discussed (1 Scutigeromorpha, 9 Lithobiomorpha, 3 Scolopendromorpha, 13
      Geophilomorpha), 21 of which are new to the island, i.e. Scutigera coleoptrata
      (Linnaeus, 1758), Lithobius (Ezembius) parvicornis (Porat, 1893), L. (E.)
      pamukkalensis Matic, 1980, L. (E.) zeylanus (Chamberlin, 1952), L. (Lithobius)
      carinatus L. Koch, 1862, L. (L.) erythrocephalus C.L. Koch, 1847, L. (Lithobius?)
      anderssoni n. sp., L. (Monotarsobius) ferganensis Trotzina, 1880, Cryptops
      (Cryptops) kosswigi (Chamberlin, 1952), C. (C.) cf. trisulcatus Brolemann, 1902,
      Dignathodon microcephalus (Lucas, 1846), Henia (Meinertia) bicarinata (Meinert,
      1870), Geophilus cf. alpinus Meinert, 1870, G cf. carpophagus Leach, 1815,
      Pachymerium ferrugineum (C.L. Koch, 1835), Schizotaenia sp., Stenotaenia naxia
      (Verhoeff, 1901), Thracophilus cilicius Attems, 1947, Nannophilus eximius
      (Meinert, 1870) and Schendyla cf. nemorensis (C.L. Koch, 1837), and another
      unidentified species of Schendylidae . As far as known, Lithobius anderssoni n.
      sp. is endemic to the island. Geographic distribution in Cyprus and ecological
      notes are given for each species. Taxonomic remarks are given for some species.

PMID- 26295109
TI  - Enchytraeidae (Oligochaeta, Annelida) from a field site in Portugal, with the
      description of five new species and a redescription of Enchylea heteroducta
      Nielsen & Christensen, 1963.
AB  - Five new species of terrestrial Enchytraeidae (Oligochaeta, Clitellata) are
      described from an experimental field area in Portugal. Achaeta coimbrensis sp.
      nov. belongs to a group of species without pyriform glands and with lateral
      spermathecal ectal pores. Fridericia sousai sp. nov., F. roembkei sp. nov., F.
      marginata sp. nov., and F. ciliotheca sp. nov. have a maximum of four chaetae per
      bundle and two spermathecal diverticula, a character combination shared by c. 30
      other species of this genus. The new Fridericia species are distinguished from
      these congeners by combinations of characters, but the ventral pattern of the
      clitellum alone is sufficient to separate the new species from each other.
      Enchylea heteroducta Nielsen & Christensen, 1963 is redescribed, this being the
      first record after the original description and the first record from a natural
      habitat. Further 16 species of enchytraeids are recorded, and there are now 32
      species of enchytraeids known from Portugal.

PMID- 26295110
TI  - Two new species of Heterophrynus Pocock, 1894 from Colombia with distribution
      notes and a new synonymy (Arachnida: Amblypygi: Phrynidae).
AB  - The genus Heterophrynus is for the first time recorded from Transandean areas.
      Heterophrynus boterorum sp. nov. and Heterophrynus silviae sp. nov. are described
      respectively from Tolima and Valle del Cauca departments, Colombia, based on
      material from the 2006 Arachnological Expedition of Museu Nacional to Colombia.
      Heterophrynus nicefori Amado & Morales, 1986, from Meta department is newly
      considered a junior subjective synonym of Phrynus batesii Butler, 1873 (currently
      in Heterophrynus). Heterophrynus is currently known from Amazon forest, Brazilian
      Cerrado, Littoral Ridge of Venezuela and Andean forests. A revised terminology is
      proposed for the constituent parts of male and female gonopods of Heterophrynus.

PMID- 26295111
TI  - A new species of extinct scops owl (Aves: Strigiformes: Strigidae: Otus) from Sao
      Miguel Island (Azores Archipelago, North Atlantic Ocean).
AB  - The extinct Sao Miguel Scops Owl Otusfrutuosoi n. sp. is described from fossil
      bones found in Gruta de Agua de Pau, a volcanic tube in Sao Miguel Island (Azores
      Archipelago, North Atlantic Ocean). It is the first extinct bird described from
      the Azores and, after the Madeiran Scops Owl (O. mauli Rando, Pieper, Alcover &
      Olson 2012a), the second extinct species of Strigiformes known in Macaronesia.
      The forelimb elements of the new taxon are shorter, the hindlimb elements are
      longer, and the pelvis is shorter and broader than in the Eurasian Scops Owl (O.
      scops Linnaeus). The new species differs from O. mauli in the smaller size of
      many of its bones, especially the ulna and tibiotarsus. Its measurements
      (estimated weight, wing area, and wing loading, and the ratio of humerus + ulna +
      carpometacarpus length/femur length) indicate weak powers of flight and ground
      dwelling habits. The latest occurrence of the new species, as evidenced by a
      radiocarbon date of 1970 +/- 40 BP from bone collagen, indicates a Late Holocene
      extinction event subsequent to 49 cal BC, and was probably linked to human
      arrival and subsequent habitat alterations.

PMID- 26295112
TI  - Revision of Gallerucida singularis species group (Coleoptera: Chrysomelidae:
      Galerucinae).
AB  - The Gallerucida singularis species group is established. Gallerucida gebieni
      Weise, status restored and G. haroldi Weise, status restored are resurrected from
      synonymy with G. singularis Harold. Lectotypes are designated for G. haroldiand G
      .tonkinensis Laboissi6ee. The species are differentiated mainly based on the
      structure of the endophallic sclerites.

PMID- 26295113
TI  - An extraordinary tribe of Tropiduchidae from the Eocene Baltic amber (Hemiptera:
      Fulgoromorpha: Fulgoroidea).
AB  - The new tribe Patollini trib. n. of the Tropiduchidae with the extinct genus
      Patollo gen. n., comprising two species Patollo natangorum sp. n. and P.
      aestiorum sp. n. from Eocene Baltic amber is described. Taxonomic placement of
      some fossil taxa ascribed to Tropiduchidae is discussed. The classification of
      Tropiduchidae is discussed, as well as phylogenetic position and fossil record of
      Tropiduchidae and related taxa.

PMID- 26295114
TI  - New species and redescriptions of the New Zealand genus Exsul Hutton (Diptera:
      Muscidae: Coenosiinae).
AB  - Exsul Hutton (Diptera, Muscidae) is revised and the genus diagnosis is enlarged.
      The female of Exsul singularis Hutton is described for the first time. The male
      and female terminalia of all species are described and illustrated. Exsul
      alfredoi sp. n. is described and illustrated and compared with the other known
      species. A key to separate the species is given.

PMID- 26295115
TI  - Comments on cladocerans of crater lakes of the Nevado de Toluca Volcano (Central
      Mexico), with the description of a new species, Alona manueli sp. nov.
AB  - Cladoceran communities of two lakes of Nevado de Toluca Volcano, Central Mexico,
      were studied. A new species of Aloninae, Alona manueli sp. nov., is described. It
      was previously confused with Palearctic Alona intermedia Sars, 1862, but clearly
      differs from it in the morphology of postabdomen, head shield and head pores, and
      thoracic limbs. Position of Alona manueli sp. nov. within the genus is unclear,
      it did not belong to any species-group within Alona s. lato. Other species
      recorded in the studied lakes are Alona ossiani Sinev, 1998, Alonella pulchella
      Herrick, 1884, Chydorus belonging to sphaericus-group, Eurycercus longirostris
      Hann, 1982 and Pleuroxus cf. denticulatus Birge, 1879.

PMID- 26295116
TI  - Stingless bees (Hymenoptera: Apidae: Meliponini) of the Indian subcontinent:
      Diversity, taxonomy and current status of knowledge.
AB  - Eight named species of stingless bees are known from the Indian subcontinent:
      Lepidotrigona arcifera (Cockerell), Lisotrigona cacciae (Nurse), Lisotrigona
      mohandasi Jobiraj & Narendran, Tetragonula aff. laeviceps (Smith), Tetragonula
      bengalensis (Cameron), Tetragonula gressitti (Sakagami), Tetragonula iridipennis
      (Smith), Tetragonula praeterita (Walker), and Tetragonula ruficornis (Smith).
      Lectotypes are newly designated for T. bengalensis and T. ruficornis. Keys,
      comparative notes, and illustrations for species identification are provided. The
      distribution of stingless bees throughout the Indian subcontinent are summarized
      and concluding that they are found in most parts of the Indian subcontinent,
      except at higher elevation or the drier interior regions. Additional collections
      and studies are urgently needed to clearly define the species limits of the
      complex "iridipennis" species group.

PMID- 26295118
TI  - Thirteen new species of the spider genus Karaops (Araneae: Selenopidae) from
      Western Australia.
AB  - Thirteen new species of the recently-described genus Karaops Crews and Harvey,
      2011 are described from Western Australia, bringing the total number of species
      of this genus to 37. The new species are K. umiida sp. nov. (female, male), K.
      nyiyaparli sp. nov. (female), K. kariyarra sp. nov. (female), K. yurlburr sp.
      nov. (female, male), K. feedtime sp. nov. (female), K. forteyi sp. nov. (female,
      male), K. yindjibarndi sp. nov. (male), K. jaburrara sp. nov. (male), K. ngarluma
      sp. nov. (male), K. nyangunarta sp. nov. (female, male), K. nyamal sp. nov.
      (female), K. banyjima sp. nov. (female) and K. yumbu sp. nov. (male). The male of
      K. inartamarta Crews and Harvey, 2011 is described for the first time, and new
      distribution records are given for this species and for K. burbidgei Crews and
      Harvey, 2011. Finally, a new key' to all of the described species of Karaops is
      provided.

PMID- 26295117
TI  - New or little known taxa of the plant bug tribe Hallodapini (Hemiptera:
      Heteroptera: Miridae: Phylinae) from Thailand, with descriptions of three new
      species of the genus Acrorrhinium Noualhier.
AB  - New or little known genera and species of the phyline plant bug tribe Hallodapini
      are documented. The genus Acrorrhinium Noualhier is reported from Thailand for
      the first time and diagnosed. Three new species, Acrorrhinium kranion, A.
      lancialium and A. tritonion, are described. The immature forms are confirmed for
      A. lancialium (5th instar) and A. tritonion (4th instar); the latter species was
      found to be associated with Hibiscus tiliaceus L. The little known hallodapines
      in Asia, Alloeomimus muiri Schuh and Clapmarius thailandana Schuh, are also
      diagnosed. An annotated check list of the Hallodapini in Thailand and color
      digital images in life for all currently known Thai species are provided.
      Hallodapus brunneus (Poppius) is reported from the Oriental Region for the first
      time.

PMID- 26295119
TI  - A new species of Megaesthesius Rathbun, 1909 (Crustacea: Brachyura:
      Chasmocarcinidae) from deep water off Western Australia.
AB  - A new species of Megaesthesius Rathbun, 1909, M. westralia, is described from
      shelf waters off Western Australia. It can be separated from its two congeners by
      differences in carapace shape and dentition, as well as differences in the male
      abdomens and gonopods.

PMID- 26295120
TI  - Pseudobranchiomysis arenae, a new genus and species of Leptomysinae (Crustacea:
      Mysida) in Argentinian sandy beaches.
AB  - A new genus of Leptomysinae Hansen, 1910, constituting a new type species for
      science, is described: Pseudobranchiomysis arenae. This new mysid is
      characterized by a combination of the following characters: antennal scale
      lanceolate and setose all around with a pointed apex, telson with apical cleft
      armed with many fine spines on the convex margins, and well-developed
      pseudobranchial lobes in male pleopods. Individuals of this species were found in
      the surf zone of two sandy beaches in Argentina and constitute a stable
      population.

PMID- 26295121
TI  - New apterous Carventinae from Sri Lanka and Southern India (Hemiptera:
      Heteroptera: Aradidae).
AB  - Two new species of apterous Carventinae are described in this paper. One belongs
      to the endemic monotypic genus Singhalaptera Heiss 2001 from Sri Lanka
      (Singhalaptera secunda n.sp.), and the other to the monotypic genus Signocoris
      Hoberlandt 1958 from Madras (Signocoris nilgiricus n.sp.). All four known species
      of both genera are illustrated and compared.

PMID- 26295122
TI  - Description of the female of Allocosa yurae (Strand, 1908) (Araneae: Lycosidae,
      Allocosinae).

PMID- 26295123
TI  - Advertisement call of Scinax strigilatus (Spix, 1824) (Anura: Hylidae) from
      southern Bahia, Brazil.

PMID- 26295124
TI  - Native aphids of New Zealand--diversity and host associations.
AB  - At least 15 species of aphids are now recognised as New Zealand natives and most
      of these are very likely to be endemic. Most native aphids belong in the
      subfamily Aphidinae (Aphidini), with a possible single species in Aphidinae
      Macrosiphini, at least two in Neophyllaphidinae and one in Taiwanaphidinae. With
      one exception, native aphids are restricted to a single host plant genus, and
      these hosts are from 13 genera and 12 plant families in the Pinales and
      Angiospermae-Eudicotyledonae, suggesting that the aphids are a remnant fauna. No
      known native aphids have host plants from the Pteridophyta or Angiospermae
      Monocotyledonae, with the possible exception of two possibly native species
      extracted from native tussock grassland turfs. Most host plant genera have some
      degree of Gondwanan distribution, but only two indigenous species are found on
      large forest trees and only one host is deciduous. Native aphids have been
      recorded from sea level to the subalpine zone, reflecting their host plant
      distributions. Sexual reproduction, followed by several parthenogenetic
      generations on the same host plant, appears to be the norm for most species. Eggs
      appear to be used for surviving winter conditions in some species and summer
      conditions in others. Native aphid distribution and abundance varies with five
      species considered to be scarce, one species localised, two species sparse and
      three relatively common based on current knowledge.

PMID- 26295125
TI  - Pseudolaguvia nubila, a new sisorid catfish (Teleostei: Sisoridae) from
      northeastern India.
AB  - This study describes Pseudolaguvia nubila, a new miniature sisorid catfish from
      the Kaladan River drainage in northeastern India. Pseudolaguvia nubila can be
      distinguished from congeners in having a combination of a mottled brown body with
      yellowish bands, a weakly projecting snout in which the premaxillary teeth are
      barely exposed when the mouth is closed, head width 19.7-21.7% standard length
      (SL), eye diameter 10.8-14.0% head length (HL), interorbital distance 25.6-31.8%
      HL, absence of a pale Y-shaped marking on the dorsal surface of the head and
      supraoccipital process, a smooth anterior edge of the dorsal spine, dorsal-fin
      spine length 16.4-19.3% SL, length of dorsal-fin base 15.1-17.3% SL, 7-8
      serrations on the anterior edge of the pectoral spine, pectoral-fin spine length
      18.1-22.0% SL, dorsal to adipose distance 13.1-16.8% SL, length of adipose-fin
      base 14.2-15.9% SL, pelvic-fin length 15.8-18.5% SL, body depth at anus 13.9
      17.1% SL, caudal-peduncle length 15.7-20.2% SL, caudal-peduncle depth 9.1-11.1%
      SL, and caudal-fin length 20.3-25.3% SL.

PMID- 26295126
TI  - A new species of the genus Ocadia (Testudines: Geoemydidae) from the middle
      Miocene of Tanegashima Island, southwestern Japan and its paleogeographic
      implications.
AB  - A new geoemydid turtle, Ocadia tanegashimensis (Testudines: Geoemydidae) is
      described on the basis of a relatively well-preserved shell from the lower middle
      Miocene of Tanegashima Island, Kagoshima Prefecture, southwestern Japan. This
      species is clearly distinguished from two congeneric species (extant O. sinensis
      and O. nipponica from the middle Pleistocene of eastern Japan) due to the
      presence of the following character states: length of the entoplastron as long as
      the interhyoplastral suture, the costals dovetailed with one another in outline,
      the third pleural overlapping only the sixth and seventh peripherals. The present
      study suggests that the initial intrageneric diversification of Ocadia began not
      later than the early Miocene in eastern Asia.

PMID- 26295127
TI  - Two new species of myxosporean parasites (Myxosporea: Bivalvulida) from gall
      bladders of Macruronus magellanicus Lonnberg, 1907 (Teleostei: Merlucciidae).
AB  - Two new species of myxosporeans are described from the gall bladders of hoki,
      Macruronus magellanicus Lonnberg, 1907, caught in the Southeast Pacific off Chile
      and in the Southwest Atlantic off the Falkland Islands. Pseudalataspora kovalevae
      n. sp. is described morphologically and genetically. Of the 12 species of
      Pseudalataspora previously described from the gall bladders of marine fish, P.
      kovalevae is most similar in morphology to P. umbraculiformis Gaevskaya and
      Kovaleva, 1984. The 18S rRNA gene sequence from P. kovalevae is the first for a
      member of the genus Pseudalataspora. Based on currently available myxosporean 18S
      rRNA gene sequence data, P. kovalevae shares greatest sequence identity with
      species of the genus Ceratomyxa (C. anko and C. pantherini). Palliatus
      magellanicus n. sp. is described morphologically only; it differs considerably in
      morphology, host species and locality from the five other Palliatus species
      described from marine fishes. A third species from the gall bladder is also
      described morphologically and genetically. On the basis of its morphology it is
      tentatively identified as Myxidium baueri Kovaleva and Gaevskaya, 1982, for which
      M. magellanicus is a new host record. Molecular analysis indicates that, of those
      species for which data are available, M. baueri is most closely related to
      Myxidium coryphaenoideum Noble, 1966 based on 18S rRNA gene sequence data, though
      support for a phylogenetic grouping is low.

PMID- 26295128
TI  - New genera of Lachesillidae (Psocodea: 'Psocoptera': Eolachesillinae:
      Graphocaeciliini) from Valle del Cauca, Colombia.
AB  - Two new related Colombian genera of Lachesillidae, including three new species,
      from the Department of Valle del Cauca, are here described and illustrated. They
      belong in the tribe Graphocaeciliini (Eolachesillinae). The new genera differ
      from the other genera in the tribe lacking ocelli, by characters of the male
      clunium, phallosome, endophallus, paraprocts, and female subgenital plate,
      gonapophyses and IX sternum. The types are deposited in the Entomological Museum
      of the Universidad del Valle (MUSENUV), in Santiago de Cali, Colombia.

PMID- 26295129
TI  - Two new species of freshwater crabs of the genus Heterochelamon Turkay & Dai,
      1997 (Crustacea: Decapoda: Brachyura: Potamidae) from Guangxi Zhuang Autonomous
      Region, southern China.
AB  - Heterochelamon tessellatum n. sp. and H. castanea n. sp. are described trom the
      Guangxi Zhuang Autonomous Region, southern China. Heterochelamon tessellatum n.
      sp. and H. castanea n. sp. are morphologically most similar to H. yangshuoense
      Turkay & Dai, 1997, and H. guangxiense Turkay & Dai, 1997, respectively. The new
      species can be differentiated from these allied species by differences in the
      shape of external orbital tooth, epibranchial tooth, and male first gonopod. The
      present study brings the number of Heterochelamon species to five. A key to
      species of the genus Heterochelamon is provided.

PMID- 26295130
TI  - Systematics of the bee subgenus Systropha (Austrosystropha) (Hymenoptera:
      Halictidae): Description of a new species and proposal of a new sex association.
AB  - Systropha is a small genus of bees belonging to Rophitinae (sister-group to all
      remaining Halictidae). Three subgenera are recognized in Systropha:
      Austrosystropha and Systrophidia that are sub-Saharan endemics, and Systropha
      s.str., which occurs in Africa and Eurasia. As a result of the rarity of
      Systropha specimens in collections and the difficulty in associating males and
      females due to sexual dimorphism, there remain numerous undescribed or
      unassociated sexes in S. (Austrosystropha). The present paper gives the
      descriptions of a new species Systropha oti sp. n. (from Kenya) and the
      previously undescribed female of S. aethiopica, both in the subgenus
      Austrosystropha. We further discuss the diagnostic features of the subgenus with
      regard to these new taxa and update the previous key to species.

PMID- 26295131
TI  - A new Early Cretaceous shore bug (Hemiptera: Heteroptera: Saldidae) from China.
AB  - A new genus Luculentsalda Zhang, Yao & Ren gen. nov. (type-species Luculentsalda
      maculosa Zhang, Yao & Ken sp. nov.) of Saldidae is described and illustrated. All
      the specimens were collected from Early Cretaceous Yixian Formation of
      Huangbanjigou, Beipiao City, Liaoning Province, China. New findings suggest that
      the subfamily Chiloxanthinae probably originated in the eastern part of Laurasia.

PMID- 26295132
TI  - The distress call of Caiman crocodilus crocodilus (Crocodylia: Alligatoridae) in
      western Amazonia, Brazil.

PMID- 26295133
TI  - Resurrection of the genus Parapsallus Wagner (Hemiptera: Heteroptera: Miridae:
      Phylinae: Phylini).

PMID- 26295134
TI  - Glioblastoma Multiforme and Lipid Nanocapsules: A Review.
AB  - Epidemiological data on central nervous system disorders call for a focus on the
      major hindrance to brain drug delivery, blood-central nervous system barriers.
      Otherwise, there is little chance of improving the short-term survival of
      patients with diseases such as glioblastoma multiforme, which is one of the brain
      disorders associated with many years of life lost. Targetable nanocarriers for
      treating malignant gliomas are a unique way to overcome low chemotherapeutic
      levels at target sites devoid of systemic toxicity. This review describes the
      currently available targetable nanocarriers, focusing particularly on one of the
      newest nanocarriers, lipid nanocapsules. All of the strategies that are likely to
      be exploited by lipid nanocapsules to bypass blood-central nervous system
      barriers, including the most recent targeting approaches (mesenchymal cells), and
      novel administration routes (convection enhanced delivery) are discussed,
      together with their most remarkable achievements in glioma-implanted animal
      models. Although these systems are promising, much research remains to be done in
      this field.

PMID- 26295135
TI  - Hyaluronic Acid-Tocopherol Succinate-Based Self-Assembling Micelles for Targeted
      Delivery of Rifampicin to Alveolar Macrophages.
AB  - We developed a target drug delivery system for the treatment of tuberculosis
      using rifampicin (RIF) incorporated into hyaluronic acid-tocopherol succinate (HA
      TS) micelles. The RIF-HA-TS micelles were physicochemically characterized and the
      cellular uptake of RIF-HA-TS micelles on murine alveolar macrophage MH-S cells
      was investigated. Furthermore, the cytokine secreting activities of the alveolar
      macrophages after treatment with RIF-HA-TS micelles were evaluated. The results
      of the studies indicate that (i) mean particle size of HA-TS micelles was in the
      range of 212-294.6 nm depending on the degree of substitution (DS) of the
      hydrophobic moiety. The incorporated RIF was sustained released from RIF loaded
      HA-TS micelles (ii) cellular uptake of RIF-HA-TS micelles was dose and energy
      dependent (iii) RIF-HA-TS micelles had a significant uptake in comparison to free
      RIF, with the highest uptake at 12 h (iv) RIF-HA-TS micelles were taken up into
      cells via phygocytosis as well as CD44 receptor-mediate endocytosis (v) beside E.
      coli lipopolysccharide (LPS), HA-TS micelles also could activate MH-S cells,
      which improved the RIF-HA-TS uptake (vi) RIF-HA-TS micelles induced higher
      concentration of Th1 cytokines than free drug, which will help to enhance the
      anti-tuberculosis activity. The results of the current studies demonstrate the
      feasibility of targeting macrophages and the possibility of using the HA-TS
      micelles for tuberculosis treatment.

PMID- 26295136
TI  - Mixed Micelles of Doxorubicin Overcome Multidrug Resistance by Inhibiting the
      Expression of P-Glycoprotein.
AB  - With the goal of overcoming multidrug resistance, DSPE-PEG (polyethylene glycol
      2000 grafted with distearoyl phosphatidylethanolamine) and TPGS (d-alpha
      tocopheryl polyethylene glycol 1000 succinate) were combined, each with a
      different inhibiting mechanism for P-glycoprotein (P-gp) expression, to create
      mixed micelles with the purpose of encapsulating the water-soluble drug,
      doxorubicin (Dox). As the molar ratio of Dox/DSPE-PEG/TPGS was 1:1:0.2, the
      encapsulation efficiency and particle size of the micelles were 98.2% and 12.8 nm
      respectively. Compared to Dox/DSPE-PEG micelles, Dox/DSPE-PEG/TPGS mixed micelles
      demonstrated enhanced in vitro cytotoxicity, drug uptake, and apoptosis for drug
      resistant H460/TaxR cancer cells. Western blot results showed that the expression
      level of P-gp significantly decreased as H460/TaxR cells were incubated with
      Dox/DSPE-PEG/TPGS mixed micelles. The anti-tumor efficacy in vivo was evaluated
      using H460/TaxR-bearing mice and showed that Dox/DSPE-PEG/TPGS mixed micelles
      were more effective at inhibiting tumor growth than Dox/DSPE-PEG micelles and
      free Dox solution. It was also found that the high efficacy of mixed micelles was
      associated with the ability to induce dramatic apoptosis of the tumor cells. In
      summary, through combining different P-gp inhibiting mechanisms, mixed micelles
      could be a promising nanocarrier for anti-cancer drugs in overcoming multidrug
      resistance.

PMID- 26295137
TI  - Targeting Epirubicin Plus Quinacrine Liposomes Modified with DSPE-PEG2000
      C(RGDfK) Conjugate for Eliminating Invasive Breast Cancer.
AB  - Recurrence of invasive breast cancer could arise from the residual cancer cells
      after comprehensive treatment. It is possible that residual invasive cancer cells
      are capable of forming highly patterned vasculogenic mimicry (VM) channels,
      leading to relapse and metastasis. In the present study, a new type of targeting
      epirubicin plus quinacrine liposomes was developed by modifying functional DSPE
      PEG2000 with C(RGDfK), a cyclic peptide containing Arg-Gly-Asp. These liposomes
      could potentially eliminate invasive breast cancer and destroy VM channels.
      Evaluations were made in human invasive breast cancer cells and their xenografts
      in nude mice. The results showed that the targeting epirubicin plus quinacrine
      liposomes could enhance the accumulation and uptake of the drugs in cancer
      tissues, kill cancer cells directly, activate apoptotic enzymes, destroy the VM
      channels and downregulate the VM channel-forming marker molecules (EphA2, FAK,
      PI3K, MMP 9, MMP 14, VE-Cad and HIF-alpha), thereby exhibiting a strong overall
      anticancer efficacy. The targeting epirubicin plus quinacrine liposomes provided
      a promising strategy to treat invasive breast cancer and to prevent the relapse
      arising from VM channels after chemotherapy.

PMID- 26295138
TI  - Self-Assembled Monomethoxy (Polyethylene Glycol)-b-P(D,L-Lactic-co-Glycolic Acid)
      b-P(L-Glutamic Acid) Hybrid-Core Nanoparticles for Intracellular pH-Triggered
      Release of Doxorubicin.
AB  - Triblock copolymers, Monomethoxy (Polyethylene glycol)-b-P(D,L-lactic-co-glycolic
      acid)-b-P(L-glutamic acid) (mPEG-PLGA-PGlu) with different molecular weights,
      were synthesized and mPEG(5k)-PLGA(20.5k)-PGlu(7.9k) were self-assembled into
      negatively charged nanoparticles with a hybrid core of PLGA and PGlu, and a
      stealth PEG shell. Because of electrostatic interaction with the negative hybrid
      core, the model drug, doxorubicin (DOX), could be easily loaded into the hybrid
      core nanoparticles with a high drug loading of ca. 25%. The hydrophobic
      interaction provided by PLGA could increase the stability of drug-loaded
      nanoparticles with no change in particle size for at least 3 days and only minor
      drug leakage (< 0.5%) in pH7.4 physiological media. Due to protonation of PGlu
      block in pH5.0 medium, the hybrid-core of these nanoparticles was destroyed, as
      shown by transmission electron microscopy, and this resulted in an increase in
      the pH-triggered release of DOX from 38.9% in pH7.4 release medium to 71% in
      pH5.0 release medium at 24 h. In vitro cytotoxicity testing involving MCF-7 and
      NCI-H460 cells showed that DOX-loaded nanoparticles were more cytotoxic to both
      types of cells than free DOX. Time-dependent cellular uptake of the drug-loaded
      nanoparticles was observed and at least 4 hours was required for rapid
      internalization through caveolinmediated endocytosis and macropinocytosis by MCF
      7 cells into the endosomes where pH-trigged release of DOX from the nanoparticles
      occurred. The hybrid-core nanoparticles represent a potentially useful
      therapeutic delivery system for cationic drugs due to their high drug loading,
      high stability in physiological media and intracellular pH-triggered release.

PMID- 26295139
TI  - PAMAM Dendrimer/pDNA Functionalized-Magnetic Iron Oxide Nanoparticles for Gene
      Delivery.
AB  - Herein, we report an easy and ingenious method to functionalize magnetic iron
      oxide nanoparticles (MNPs) with plasmid DNA (pDNA) to obtain nanohybrid systems
      suitable for nucleic acid therapy. The nanohybrids were prepared by combining
      complexes of dendrimers and pDNA (dendriplexes) and poly(styrene) sulfonate
      coated MNPs through electrostatic interactions. The effects of the dendrimer
      generation (generations 2, 4 and 6) and the amine to phosphate group (N/P) ratio
      on the hydrodynamic diameter, zeta potential, cell viability, cellular
      internalization and transfection efficiency of the nanohybrids were
      systematically investigated at different transfection conditions (including
      incubation time, pDNA concentration, presence or absence of an external magnetic
      field, and presence or absence of fetal bovine serum). The results confirmed that
      the nanohybrids were able to transfect NIH 3T3 cells, and that the level of gene
      expression (the luciferase protein reporter gene was used) was strongly dependent
      on the dendrimer generation, the N/P ratio, and the pDNA concentration. The best
      system was based on dendriplex-coated MNPs formed by generation 6 dendrimers at
      an N/P ratio of 10 that, at optimized conditions, led to a gene expression level
      which was not significantly different from that obtained only using dendriplexes.
      In summary, a coherent set of results was reached indicating the potential of the
      developed nanohybrids as effective gene delivery nanomaterials.

PMID- 26295140
TI  - Folic Acid Linked Chondroitin Sulfate-Polyethyleneimine Copolymer Based Gene
      Delivery System.
AB  - In our previous study, chondroitin sulfate-polyethylenimine copolymers (CP) have
      been synthesized and confirmed as potential gene delivery vectors. Efficient gene
      transfection is realized by chondroitin sulfate (ChS) that promotes CD44-
      mediated endocytosis and enhances the cellular uptake of CP/pDNA polyplexes
      besides clathrin-mediated endocytosis. In this study, the CP was functionalized
      with a folic acid (FA) molecule. This ancillary ligand allows polyplexes to bind
      with folate receptors (FR) in addition to the CD44 receptor. We conjugated FA
      linked polyethylene glycol (FA-PEG) onto CP (FPCP) for tumor targeting and also
      synthesized mPEG-CP (MPCP) for comparison. The in vitro cell tests of
      polymer/pDNA polyplexes were done in FR-expressed U87 and FR-deficient A549
      cells. The polymers exhibited less cytotoxicity than PEI-10K as well as PEI-25K
      against U87 and A549 cells. The transfection efficiency of FPCP/pDNA was higher
      than those of MPCP/pDNA and CP/pDNA. The cellular uptake pathways of FPCP/pDNA
      were tested in the cells in the presence of different endocytic chemical
      inhibitors. The CD44-, folate-, and caveolae-mediated pathways are involved in
      internalization of FPCP/pDNA. Recognition of FPCP to those receptors on the tumor
      surface is beneficial for enhanced cellular uptake of FPCP/pDNA, resulting in
      higher transgene expression than CP/pDNA and MPCP/pDNA.

PMID- 26295141
TI  - Dual-Ligand Modified Polymer-Lipid Hybrid Nanoparticles for Docetaxel Targeting
      Delivery to Her2/neu Overexpressed Human Breast Cancer Cells.
AB  - In this study, a dual-ligand polymer-lipid hybrid nanoparticle drug delivery
      vehicle comprised of an anti-HER2/neu peptide (AHNP) mimic with a modified HIV-1
      Tat (mTAT) was established for the targeted treatment of Her2/neu-overexpressing
      cells. The resultant dual-ligand hybrid nanoparticles (NPs) consisted of a
      poly(lactide-co-glycolide) core, a near 90% surface coverage of the lipid
      monolayer, and a 5.7 nm hydrated polyethylene glycol shell. Ligand density
      optimization study revealed that cellular uptake efficiency of the hybrid NPs
      could be manipulated by controlling the surface-ligand densities. Furthermore,
      the cell uptake kinetics and mechanism studies showed that the dual-ligand
      modifications of hybrid NPs altered the cellular uptake pathway from caveolae
      mediated endocytosis (CvME) to the multiple endocytic pathways, which would
      significantly enhance the NP internalization. Upon the systemic investigation of
      the cellular uptake behavior of dual-ligand hybrid NPs, docetaxel (DTX), a
      hydrophobic anticancer drug, was successfully encapsulated into dual-ligand
      hybrid NPs with high drug loading for Her2/neu-overexpressing SK-BR-3 breast
      cancer cell treatment. The DTX-loaded dual-ligand hybrid NPs showed a decreased
      burst release and a more gradual sustained drug release property. Because of the
      synergistic effect of dual-ligand modification, DTX-loaded dual-ligand hybrid NPs
      exerted substantially better therapeutic potency against SK-BR-3 cancer cells
      than other NP formulations and free DTX drugs. These results demonstrate that the
      dual-ligand hybrid NPs could be a promising vehicle for targeted drug delivery to
      treat breast cancer.

PMID- 26295142
TI  - Improved Peptide-Targeted Liposome Design Through Optimized Peptide
      Hydrophilicity, Ethylene Glycol Linker Length, and Peptide Density.
AB  - Ligand-targeted liposomes are increasingly used as drug delivery carriers for
      cancer therapy, yet have not consistently produced successful outcomes. Here, we
      demonstrated the significant enhancement in cellular uptake of peptide-targeted
      liposomes by simultaneously increasing the hydrophilicity of the targeting
      peptide, optimizing the EG peptide-linker length, and using appropriate peptide
      surface density. We analyzed these parameters in a HER2-overexpressing breast
      cancer model system where the liposomes were functionalized with one of four
      distinct HER2-antagonist peptides to evaluate cellular uptake. Our results
      demonstrated that including a short oligolysine chain adjacent to the targeting
      peptide sequence effectively improved cellular uptake -6-10 fold when using an
      EG6-EG18 linker depending on the selected antagonist peptide. Uptake efficiency
      reached a maximum and a plateau with -2% peptide density with higher observed
      sensitivity at lower peptide densities for the more hydrophilic peptides. Taken
      together, these findings demonstrated the importance of optimizing liposome
      design for improved cellular uptake.

PMID- 26295143
TI  - Folate Receptor-Targeted Dendrimer-Methotrexate Conjugate for Inflammatory
      Arthritis.
AB  - Generation 5 (G5) poly(amidoamide) (PAMAM) dendrimers are synthetic polymers that
      have been broadly applied as drug delivery carriers. Methotrexate (MTX), an anti
      folate metabolite, has been successfully used as an anti-inflammatory drug to
      treat rheumatoid arthritis (RA) in the clinic. In this study, we examine the
      therapeutic efficacy of G5 PAMAM dendrimer methotrexate conjugates (G5-MTX) that
      also have folic acid (FA) conjugated to the G5-MTX (G5-FA-MTX) to target
      inflammation-activated folate receptors overexpressing macrophages. These cells
      are thought to play an important role in the development of RA. With G5 serving
      as a control, the in vitro binding affinities of G5-FA-MTX and G5-MTX to
      activated macrophages were assessed in RAW264.7, NR8383 and primary rat
      peritoneal macrophages. The results indicated that the binding of either
      conjugate to macrophages was concentration- and temperature-dependent and could
      be blocked by the presence of 6.25 mM free FA (p < 0.005). The preventive effects
      of G5-MTX and G5-FA-MTX conjugates on the development of arthritis were explored
      on an adjuvant-induced inflammatory arthritis model and had similar preventive
      effects in inflammatory arthritis at a MTX equivalent dose of 4.95 MUmol/kg.
      These studies indicated that when multiples of MTX are conjugated on dendritic
      polymers, they specifically bind to folate receptor overexpressing macrophages
      and have comparable anti-inflammatory effects to folate targeted MTX conjugated
      polymers.

PMID- 26295144
TI  - Photoacoustic- and Magnetic Resonance-Guided Photothermal Therapy and Tumor
      Vasculature Visualization Using Theranostic Magnetic Gold Nanoshells.
AB  - Nanoparticle based image-guided therapy is an emerging technology for cancer in
      recent years. Here, we report simultaneous photoacoustic (PA)- and magnetic
      resonance (MR)-guided photothermal ablation (PTA) therapy using multifunctional
      superparamagnetic iron oxide-containing gold nanoshells (SPIO@AuNS). Based on the
      intrinsic high near-infrared optical absorbance and strong magnetic property of
      SPIO@AuNS, we carried out in vivo dual-modality PA-MR imaging of mouse tumors. PA
      and MR-guided imaging can monitor therapeutic effect after photothermal therapy
      mediated by our multifunctional nanomaterial. In addition, using our pulsed laser
      PA technique, we also observe a clearer structure of the tumor vasculature after
      intravenously administration SPIO@AuNS. The novel dual PA-MRI image-guided PTA
      therapy provides a promising new platform for cancer diagnosis and treatment
      simultaneously.

PMID- 26295145
TI  - Nano-in-Micro Self-Reporting Hydrogel Constructs.
AB  - Highly reproducible Nano-in-Micro constructs are fabricated to provide a well
      defined and self-reporting biomimetic environment for hepatocytes. Based on a
      protein/hydrogel formulation with controlled shape, size and composition, the
      constructs enable efficient nutrient exchange and provide an adhesive 3D
      framework to cells. Co-encapsulation of hepatocytes and ratiometric optical
      nanosensors with pH sensitivity in the physiological range allows continuous
      monitoring of the microenvironment. The lobule-sized microbeads are fabricated
      using an automated droplet generator, Sphyga (Spherical Hydrogel Generator)
      combining alginate, collagen, decellularized hepatic tissue, pH-nanosensors and
      hepatocytes. The pH inside the Nano-in-Micro constructs is monitored during
      culture, while assaying media for hepatic function and vitality markers. Although
      the local pH changes by several units during bead fabrication, when encapsulated
      cells are most likely to undergo stress, it is stable and buffered by cell
      culture media thereafter. Albumin secretion and urea production are significantly
      higher in the microbeads compared with controls, indicating that the encapsulated
      Nano-in-Micro environment is conducive to enhanced hepatic function.

PMID- 26295146
TI  - Epigallocatechin-3-O-Gallate-Loaded Poly(lactic-co-glycolic acid) Fibrous Sheets
      as Anti-Adhesion Barriers.
AB  - Epigallocatechin-3-O-gallate (EGCG), the main polyphenolic component of green
      tea, has a wide range of pharmacological activities, including antioxidant, anti
      inflammatory, and anti-fibrotic effects. In this study, EGCG-loaded poly(lactic
      co-glycolic acid) (PLGA) sheets were prepared by electrospinning nanofibers and
      evaluating their potential as tissue-adhesion barriers. EGCG-loaded PLGA (E-PLGA)
      fibrous sheets were electrospun from a PLGA solution containing 8% (w/v) EGCG.
      The average diameter of E-PLGA fibers was 397 +/- 159 nm, which was comparable to
      that of pure PLGA fibers (459 +/- 154 nm). EGCG was uniformly dispersed in E-PLGA
      sheets without direct chemical interactions. E-PLGA fibrous sheets showed
      sustained release of EGCG by controlled diffusion and PLGA degradation. The
      attachment and proliferation of L-929 fibroblastic cells were significantly (p <
      0.05) suppressed in E-PLGA sheets. Furthermore, E-PLGA fibrous sheets did not
      induce any inflammatory response to J774A.1 macrophages. The anti-adhesion
      efficacy of E-PLGA fibrous sheets was evaluated in the intraperitoneal adhesion
      model in rats. Two weeks after surgical treatment, macroscopic adhesion (extent
      and severity) scores and histopathological tissue responses of E-PLGA fibrous
      sheets were significantly lower than those of non-treated controls and pure PLGA
      sheets. The results suggest that the scores are comparable, and in some cases
      superior, to those of other commercialized tissue-adhesion barriers. In
      conclusion, our study findings suggest that E-PLGA fibrous sheets may be
      exploited as potential tissue-adhesion barriers for the prevention of post
      surgical adhesion formation.

PMID- 26295147
TI  - Mucoadhesive Amphiphilic Methacrylic Copolymer-Functionalized Poly(epsilon
      caprolactone) Nanocapsules for Nose-to-Brain Delivery of Olanzapine.
AB  - Nose-to-brain drug delivery has been proposed to overcome the low absorption of
      drugs in central nervous system due to the absence of brain-blood barrier in the
      olfactory nerve pathway. However, the presence of a mucus layer and quick
      clearance limit the use of this route. Herein, amphiphilic methacrylic copolymer
      functionalized poly(epsilon-caprolactone) nanocapsules were proposed as a
      mucoadhesive system to deliver olanzapine after intranasal administration. In
      vitro evaluations showed that these nanocapsules were able to interact with mucin
      (up to 17% of increment in particle size and 30% of reduction of particle
      concentration) and nasal mucosa (2-fold higher force for detaching), as well as
      to increase the retention of olanzapine (about 40%) on the nasal mucosa after
      continuous wash. The olanzapine-loaded amphiphilic methacrylic copolymer
      functionalized PCL nanocapsules enhanced the amount of drug in the brain of rats
      (1.5-fold higher compared to the drug solution). In accordance with this finding,
      this formulation improved the prepulse inhibition impairment induced by
      apomorphine, which is considered as an operational measure of pre-attentive
      sensorimotor gating impairment present in schizophrenia. Besides,
      nanoencapsulated olanzapine did not affect the nasal mucosa integrity after
      repeated doses. These data evidenced that the designed nanocapsules are a
      promising mucoadhesive system for nose-to-brain delivery of drugs.

PMID- 26295148
TI  - Nanoencapsulation Improves Relative Bioavailability and Antipsychotic Effect of
      Olanzapine in Rats.
AB  - This study aimed to investigate the pharmacokinetics, tissue distribution and
      antipsychotic activity of olanzapine administered as free drug (OLA-FREE) or
      loaded into lipid-core nanocapsules (OLA-LNC). OLA-LNC were successfully
      developed with a particle size of 142 +/- 4 nm and a zeta potential of -19.6 +/-
      0.6 mV. Pharmacokinetics and tissue distribution studies were carried out after
      the administration of free and nanoencapsulated olanzapine (10 mg/kg) by
      intraperitoneal route to male Wistar rats. Higher olanzapine concentrations and
      AUC(0-12 h) were found in plasma and tissues evaluated after the administration
      of OLA-LNC compared to the drug in the free form, resulting in a relative
      bioavailability of 226.7% in the plasma. As a result olanzapine loaded lipid-core
      nanocapsules presented pronounced and long-lasting effects on central nervous
      system. These nanocapsules (10 mg/kg, i.p.) significantly diminished the
      stereotyped behavior induced by D,L-amphetamine up to 12 hours whereas olanzapine
      free-form (10 mg/kg, i.p.) was effective during 03 hours only. Moreover,
      olanzapine loaded lipid-core nanocapsules (1.0 mg/kg, i.p.) have shown a marked
      sedative effect and also prevented the prepulse inhibition disruption induced by
      apomorphine at lower dose than olanzapine in free-form (2.5 mg/kg, i.p.).
      Herewith, we point to the nanoencapsulation as a strategy for reducing the
      concentration of olanzapine in pharmaceutical formulations.

PMID- 26295149
TI  - RNA-Seq Analysis of Abdominal Fat Reveals Differences between Modern Commercial
      Broiler Chickens with High and Low Feed Efficiencies.
AB  - For economic and environmental reasons, chickens with superior feed efficiency
      (FE) are preferred in the broiler chicken industry. High FE (HFE) chickens
      typically have reduced abdominal fat, the major adipose tissue in chickens. In
      addition to its function of energy storage, adipose tissue is a metabolically
      active organ that also possesses endocrine and immune regulatory functions. It
      plays a central role in maintaining energy homeostasis. Comprehensive
      understanding of the gene expression in the adipose tissue and the biological
      basis of FE are of significance to optimize selection and breeding strategies.
      Through gene expression profiling of abdominal fat from high and low FE (LFE)
      commercial broiler chickens, the present study aimed to characterize the
      differences of gene expression between HFE and LFE chickens. mRNA-seq analysis
      was carried out on the total RNA of abdominal fat from 10 HFE and 12 LFE
      commercial broiler chickens, and 1.48 billion of 75-base sequence reads were
      generated in total. On average, 11,565 genes were expressed (>5
      reads/gene/sample) in the abdominal fat tissue, of which 286 genes were
      differentially expressed (DE) at q (False Discover Rate) < 0.05 and fold change >
      1.3 between HFE and LFE chickens. Expression levels from RNA-seq were confirmed
      with the NanoString nCounter analysis system. Functional analysis showed that the
      DE genes were significantly (p < 0.01) enriched in lipid metabolism, coagulation,
      and immune regulation pathways. Specifically, the LFE chickens had higher
      expression of lipid synthesis genes and lower expression of triglyceride
      hydrolysis and cholesterol transport genes. In conclusion, our study reveals the
      overall differences of gene expression in the abdominal fat from HFE and LFE
      chickens, and the results suggest that the divergent expression of lipid
      metabolism genes represents the major differences. 

PMID- 26295150
TI  - Impact of Molecular Epidemiology and Reduced Susceptibility to Glycopeptides and
      Daptomycin on Outcomes of Patients with Methicillin-Resistant Staphylococcus
      aureus Bacteremia.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia was
      associated with high mortality, but the risk factors associated with mortality
      remain controversial. METHODS: A retrospective cohort study was designed. All
      patients with MRSA bacteremia admitted were screened and collected for their
      clinical presentations and laboratory characteristics. Minimum inhibitory
      concentration (MIC) and staphylococcal cassette chromosome mec (SCCmec) type of
      bacterial isolates were determined. Risk factors for mortality were analyzed.
      RESULTS: Most MRSA isolates from the 189 enrolled patients showed reduced
      susceptibility to antibiotics, including MIC of vancomycin >= 1.5 mg/L (79.9%),
      teicoplanin >= 2 mg/L (86.2%), daptomycin >= 0.38 mg/L (73.0%) and linezolid >=
      1.5 mg/L (64.0%). MRSA with vancomycin MIC >= 1.5 mg/L and inappropriate initial
      therapy were the two most important risk factors for mortality (both P < 0.05;
      odds ratio = 7.88 and 6.78). Hospital-associated MRSA (HA-MRSA), carrying SCCmec
      type I, II, or III, was associated with reduced susceptibility to vancomycin,
      teicoplanin or daptomycin and also with higher attributable mortality (all P <
      0.05). Creeping vancomycin MIC was linked to higher MIC of teicoplanin and
      daptomycin (both P < 0.001), but not linezolid (P = 0.759). CONCLUSIONS: Giving
      empirical broad-spectrum antibiotics for at least 5 days to treat catheter
      related infections, pneumonia, soft tissue infection and other infections was the
      most important risk factor for acquiring subsequent HA-MRSA infection. Choice of
      effective anti-MRSA agents for treating MRSA bacteremia should be based on MIC of
      vancomycin, teicoplanin and daptomycin. Initiation of an effective anti-MRSA
      agent without elevated MIC in 2 days is crucial for reducing mortality.

PMID- 26295151
TI  - Advantages of Task-Specific Multi-Objective Optimisation in Evolutionary
      Robotics.
AB  - The application of multi-objective optimisation to evolutionary robotics is
      receiving increasing attention. A survey of the literature reveals the different
      possibilities it offers to improve the automatic design of efficient and adaptive
      robotic systems, and points to the successful demonstrations available for both
      task-specific and task-agnostic approaches (i.e., with or without reference to
      the specific design problem to be tackled). However, the advantages of multi
      objective approaches over single-objective ones have not been clearly spelled out
      and experimentally demonstrated. This paper fills this gap for task-specific
      approaches: starting from well-known results in multi-objective optimisation, we
      discuss how to tackle commonly recognised problems in evolutionary robotics. In
      particular, we show that multi-objective optimisation (i) allows evolving a more
      varied set of behaviours by exploring multiple trade-offs of the objectives to
      optimise, (ii) supports the evolution of the desired behaviour through the
      introduction of objectives as proxies, (iii) avoids the premature convergence to
      local optima possibly introduced by multi-component fitness functions, and (iv)
      solves the bootstrap problem exploiting ancillary objectives to guide evolution
      in the early phases. We present an experimental demonstration of these benefits
      in three different case studies: maze navigation in a single robot domain,
      flocking in a swarm robotics context, and a strictly collaborative task in
      collective robotics. 

PMID- 26295152
TI  - Changes in Postural Syntax Characterize Sensory Modulation and Natural Variation
      of C. elegans Locomotion.
AB  - Locomotion is driven by shape changes coordinated by the nervous system through
      time; thus, enumerating an animal's complete repertoire of shape transitions
      would provide a basis for a comprehensive understanding of locomotor behaviour.
      Here we introduce a discrete representation of behaviour in the nematode C.
      elegans. At each point in time, the worm's posture is approximated by its closest
      matching template from a set of 90 postures and locomotion is represented as
      sequences of postures. The frequency distribution of postural sequences is heavy
      tailed with a core of frequent behaviours and a much larger set of rarely used
      behaviours. Responses to optogenetic and environmental stimuli can be quantified
      as changes in postural syntax: worms show different preferences for different
      sequences of postures drawn from the same set of templates. A discrete
      representation of behaviour will enable the use of methods developed for other
      kinds of discrete data in bioinformatics and language processing to be harnessed
      for the study of behaviour. 

PMID- 26295153
TI  - Correction: Changes in Soil Physical and Chemical Properties in Long Term
      Improved Natural and Traditional Agroforestry Management Systems of Cacao
      Genotypes in Peruvian Amazon.

PMID- 26295154
TI  - How Rainfall Variation Influences Reproductive Patterns of African Savanna
      Ungulates in an Equatorial Region Where Photoperiod Variation Is Absent.
AB  - In high temperate latitudes, ungulates generally give birth within a narrow time
      window when conditions are optimal for offspring survival in spring or early
      summer, and use changing photoperiod to time conceptions so as to anticipate
      these conditions. However, in low tropical latitudes day length variation is
      minimal, and rainfall variation makes the seasonal cycle less predictable.
      Nevertheless, several ungulate species retain narrow birth peaks under such
      conditions, while others show births spread quite widely through the year. We
      investigated how within-year and between-year variation in rainfall influenced
      the reproductive timing of four ungulate species showing these contrasting
      patterns in the Masai Mara region of Kenya. All four species exhibited birth
      peaks during the putative optimal period in the early wet season. For hartebeest
      and impala, the birth peak was diffuse and offspring were born throughout the
      year. In contrast, topi and warthog showed a narrow seasonal concentration of
      births, with conceptions suppressed once monthly rainfall fell below a threshold
      level. High rainfall in the previous season and high early rains in the current
      year enhanced survival into the juvenile stage for all the species except impala.
      Our findings reveal how rainfall variation affecting grass growth and hence
      herbivore nutrition can govern the reproductive phenology of ungulates in
      tropical latitudes where day length variation is minimal. The underlying
      mechanism seems to be the suppression of conceptions once nutritional gains
      become insufficient. Through responding proximally to within-year variation in
      rainfall, tropical savanna ungulates are less likely to be affected adversely by
      the consequences of global warming for vegetation phenology than northern
      ungulates showing more rigid photoperiodic control over reproductive timing. 

PMID- 26295155
TI  - Variable Classification of Drug-Intoxication Suicides across US States: A Partial
      Artifact of Forensics?
AB  - BACKGROUND: The 21st-century epidemic of pharmaceutical and other drug
      intoxication deaths in the United States (US) has likely precipitated an increase
      in misclassified, undercounted suicides. Drug-intoxication suicides are highly
      prone to be misclassified as accident or undetermined. Misclassification
      adversely impacts suicide and other injury mortality surveillance, etiologic
      understanding, prevention, and hence clinical and public health policy formation
      and practice. OBJECTIVE: To evaluate whether observed variation in the relative
      magnitude of drug-intoxication suicides across US states is a partial artifact of
      the scope and quality of toxicological testing and type of medicolegal death
      investigation system. METHODS: This was a national, state-based, ecological study
      of 111,583 drug-intoxication fatalities, whose manner of death was suicide,
      accident, or undetermined. The proportion of (nonhomicide) drug-intoxication
      deaths classified by medical examiners and coroners as suicide was analyzed
      relative to the proportion of death certificates citing one or more specific
      drugs and two types of state death investigation systems. Our model incorporated
      five sociodemographic covariates. Data covered the period 2008-2010, and derived
      from NCHS's Multiple Cause-of-Death public use files. RESULTS: Across states, the
      proportion of drug-intoxication suicides ranged from 0.058 in Louisiana to 0.286
      in South Dakota and the rate from 1 per 100,000 population in North Dakota to 4
      in New Mexico. There was a low correlation between combined accident and
      undetermined drug-intoxication death rates and corresponding suicide rates
      (Spearman's rho = 0.38; p<0.01). Citation of 1 or more specific drugs on the
      death certificate was positively associated with the relative odds of a state
      classifying a nonhomicide drug-intoxication death as suicide rather than accident
      or undetermined, adjusting for region and type of state death investigation
      system (odds ratio, 1.062; 95% CI,1.016-1.110). Region, too, was a significant
      predictor. Relative to the South, a 10% increase in drug citation was associated
      with 43% (95% CI,11%-83%), 41% (95% CI,7%-85%), and 33% (95% CI,1%-76%) higher
      odds of a suicide classification in the West, Midwest, and Northeast,
      respectively. CONCLUSION: Large interstate variation in the relative magnitude of
      nonhomicide drug-intoxication deaths classified as suicide by medical examiners
      and coroners in the US appears partially an artifact of geographic region and
      degree of toxicological assessment in the case ascertainment process. Etiologic
      understanding and prevention of drug-induced suicides and other drug-intoxication
      deaths first require rigorous standardization involving accurate concepts,
      definitions, and case ascertainment.

PMID- 26295157
TI  - An Analysis of Peer-Reviewed Scores and Impact Factors with Different Citation
      Time Windows: A Case Study of 28 Ophthalmologic Journals.
AB  - BACKGROUND: An important attribute of the traditional impact factor was the
      controversial 2-year citation window. So far, several scholars have proposed
      using different citation time windows for evaluating journals. However, there is
      no confirmation whether a longer citation time window would be better. How did
      the journal evaluation effects of 3IF, 4IF, and 6IF comparing with 2IF and 5IF?
      In order to understand these questions, we made a comparative study of impact
      factors with different citation time windows with the peer-reviewed scores of
      ophthalmologic journals indexed by Science Citation Index Expanded (SCIE)
      database. METHODS: The peer-reviewed scores of 28 ophthalmologic journals were
      obtained through a self-designed survey questionnaire. Impact factors with
      different citation time windows (including 2IF, 3IF, 4IF, 5IF, and 6IF) of 28
      ophthalmologic journals were computed and compared in accordance with each impact
      factor's definition and formula, using the citation analysis function of the Web
      of Science (WoS) database. An analysis of the correlation between impact factors
      with different citation time windows and peer-reviewed scores was carried out.
      RESULTS: Although impact factor values with different citation time windows were
      different, there was a high level of correlation between them when it came to
      evaluating journals. In the current study, for ophthalmologic journals' impact
      factors with different time windows in 2013, 3IF and 4IF seemed the ideal ranges
      for comparison, when assessed in relation to peer-reviewed scores. In addition,
      the 3-year and 4-year windows were quite consistent with the cited peak age of
      documents published by ophthalmologic journals. RESEARCH LIMITATIONS: Our study
      is based on ophthalmology journals and we only analyze the impact factors with
      different citation time window in 2013, so it has yet to be ascertained whether
      other disciplines (especially those with a later cited peak) or other years would
      follow the same or similar patterns. ORIGINALITY/ VALUE: We designed the survey
      questionnaire ourselves, specifically to assess the real influence of journals.
      We used peer-reviewed scores to judge the journal evaluation effect of impact
      factors with different citation time windows. The main purpose of this study was
      to help researchers better understand the role of impact factors with different
      citation time windows in journal evaluation.

PMID- 26295156
TI  - The Mitochondrial Genomes of Aquila fasciata and Buteo lagopus (Aves,
      Accipitriformes): Sequence, Structure and Phylogenetic Analyses.
AB  - The family Accipitridae is one of the largest groups of non-passerine birds,
      including 68 genera and 243 species globally distributed. In the present study,
      we determined the complete mitochondrial sequences of two species of accipitrid,
      namely Aquila fasciata and Buteo lagopus, and conducted a comparative mitogenome
      analysis across the family. The mitogenome length of A. fasciata and B. lagopus
      are 18,513 and 18,559 bp with an A + T content of 54.2% and 55.0%, respectively.
      For both the two accipitrid birds mtDNAs, obvious positive AT-skew and negative
      GC-skew biases were detected for all 12 PCGs encoded by the H strand, whereas the
      reverse was found in MT-ND6 encoded by the L strand. One extra nucleotide'C'is
      present at the position 174 of MT-ND3 gene of A. fasciata, which is not observed
      at that of B. lagopus. Six conserved sequence boxes in the Domain II, named boxes
      F, E, D, C, CSBa, and CSBb, respectively, were recognized in the CRs of A.
      fasciata and B. lagopus. Rates and patterns of mitochondrial gene evolution
      within Accipitridae were also estimated. The highest dN/dS was detected for the
      MT-ATP8 gene (0.32493) among Accipitridae, while the lowest for the MT-CO1 gene
      (0.01415). Mitophylogenetic analysis supported the robust monophyly of
      Accipitriformes, and Cathartidae was basal to the balance of the order. Moreover,
      we performed phylogenetic analyses using two other data sets (two mitochondrial
      loci, and combined nuclear and mitochondrial loci). Our results indicate that the
      subfamily Aquilinae and all currently polytypic genera of this subfamily are
      monophyletic. These two novel mtDNA data will be useful in refining the
      phylogenetic relationships and evolutionary processes of Accipitriformes. 

PMID- 26295158
TI  - Multidrug Resistance-Associated Protein 2 Expression Is Upregulated by Adenosine
      5'-Triphosphate in Colorectal Cancer Cells and Enhances Their Survival to
      Chemotherapeutic Drugs.
AB  - Extracellular adenosine 5'-triphosphate (ATP) is a signaling molecule that
      induces a plethora of effects ranging from the regulation of cell proliferation
      to modulation of cancerous cell behavior. In colorectal cancer, ATP was reported
      to stimulate epithelial cell proliferation and possibly promote resistance to
      anti-cancer treatments. However, the exact role of this danger-signaling molecule
      on cancerous intestinal epithelial cells (IECs) in response to chemotherapeutic
      agents remains unknown. To address how ATP may influence the response of
      cancerous IECs to chemotherapeutic agents, we used Caco-2 cells, which display
      enterocyte-like features, to determine the effect of ATP on the expression of
      multidrug resistance-associated protein 2 (MRP2). Gene and protein expression
      were determined by quantitative real-time PCR (qRT-PCR) and Western blotting.
      Resistance to etoposide, cisplatin and doxorubicin was determined by MTT assays
      in response to ATP stimulation of Caco-2 cells and in cells for which MRP2
      expression was down-regulated by shRNA. ATP increased the expression of MRP2 at
      both the mRNA and protein levels. MRP2 expression involved an ATP-dependent
      stimulation of the MEK/ERK signaling pathway that was associated with an increase
      in relative resistance of Caco-2 cells to etoposide. Abolition of MRP2 expression
      using shRNA significantly reduced the protective effect of MRP2 toward etoposide
      as well as to cisplatin and doxorubicin. This study describes the mechanism by
      which ATP may contribute to the chemoresistance of cancerous IECs in colorectal
      cancer. Given the heterogeneity of colorectal adenocarcinoma responses to anti
      cancer drugs, these findings call for further study to understand the role of P2
      receptors in cancer drug therapy and to develop novel therapies aimed at
      regulating P2 receptor activity. 

PMID- 26295160
TI  - Measuring Maternal Mortality: Three Case Studies Using Verbal Autopsy with
      Different Platforms.
AB  - BACKGROUND: Accurate measurement of maternal mortality is needed to develop a
      greater understanding of the scale of the problem, to increase effectiveness of
      program planning and targeting, and to track progress. In the absence of good
      quality vital statistics, interim methods are used to measure maternal mortality.
      The purpose of this study is to document experience with three community-based
      interim methods that measure maternal mortality using verbal autopsy. METHODS:
      This study uses a post-census mortality survey, a sample vital registration with
      verbal autopsy, and a large-scale household survey to summarize the measures of
      maternal mortality obtained from these three platforms, compares and contrasts
      the different methodologies employed, and evaluates strengths and weaknesses of
      each approach. Included is also a discussion of issues related to death
      identification and classification, estimating maternal mortality ratios and
      rates, sample sizes and periodicity of estimates, data quality, and cost.
      RESULTS: The sample sizes vary considerably between the three data sources and
      the number of maternal deaths identified through each platform was small. The
      proportion of deaths to women of reproductive age that are maternal deaths ranged
      from 8.8% to 17.3%. The maternal mortality rate was estimable using two of the
      platforms while obtaining an estimate of the maternal mortality ratio was only
      possible using one of the platforms. The percentage of maternal deaths due to
      direct obstetric causes ranged from 45.2% to 80.4%. CONCLUSIONS: This study
      documents experiences applying standard verbal autopsy methods to estimate
      maternal mortality and confirms that verbal autopsy is a feasible method for
      collecting maternal mortality data. None of these interim methods are likely to
      be suitable for detecting short term changes in mortality due to prohibitive
      sample size requirements, and thus, comprehensive and continuous civil
      registration systems to provide high quality vital statistics are essential in
      the long-term.

PMID- 26295159
TI  - Towards a Science of Community Stakeholder Engagement in Biomedical HIV
      Prevention Trials: An Embedded Four-Country Case Study.
AB  - OBJECTIVES: Broad international guidelines and studies in the context of
      individual clinical trials highlight the centrality of community stakeholder
      engagement in conducting ethically rigorous HIV prevention trials. We explored
      and identified challenges and facilitators for community stakeholder engagement
      in biomedical HIV prevention trials in diverse global settings. Our aim was to
      assess and deepen the empirical foundation for priorities included in the GPP
      guidelines and to highlight challenges in implementation that may merit further
      attention in subsequent GPP iterations. METHODS: From 2008-2012 we conducted an
      embedded, multiple case study centered in Thailand, India, South Africa and
      Canada. We conducted in-depth interviews and focus groups with respondents from
      different trial-related subsystems: civil society organization representatives,
      community advocates, service providers, clinical trialists/researchers, former
      trial participants, and key HIV risk populations. Interviews/focus groups were
      recorded, and coded using thematic content analysis. After intra-case analyses,
      we conducted cross-case analysis to contrast and synthesize themes and sub-themes
      across cases. Lastly, we applied the case study findings to explore and assess
      UNAIDS/AVAC GPP guidelines and the GPP Blueprint for Stakeholder Engagement.
      RESULTS: Across settings, we identified three cross-cutting themes as essential
      to community stakeholder engagement: trial literacy, including lexicon challenges
      and misconceptions that imperil sound communication; mistrust due to historical
      exploitation; and participatory processes: engaging early; considering the
      breadth of "community"; and, developing appropriate stakeholder roles. Site
      specific challenges arose in resource-limited settings and settings where trials
      were halted. CONCLUSIONS: This multiple case study revealed common themes
      underlying community stakeholder engagement across four country settings that
      largely mirror GPP goals and the GPP Blueprint, as well as highlighting
      challenges in the implementation of important guidelines. GPP guidance documents
      could be strengthened through greater focus on: identifying and addressing the
      community-specific roots of mistrust and its impact on trial literacy activities;
      achieving and evaluating representativeness in community stakeholder groups; and
      addressing the impact of power and funding streams on meaningful engagement and
      independent decision-making.

PMID- 26295161
TI  - Recent Developments in Computational Methods for De Novo Peptide Sequencing from
      Tandem Mass Spectrometry (MS/MS).
AB  - Tandem mass spectrometry (MS/MS) has emerged as a major technology for peptide
      sequencing. Typically, there are three kinds of methods for the peptide
      sequencing: database searching, peptide tagging, and de novo sequencing. De novo
      sequencing has drawn increasing attention because of its independence from
      existing protein databases and potential for identifying new proteins, proteins
      resulting from mutations, proteins with unexpected modifications and so on.
      Recently, with the improvements in the accuracy of MS/MS and development of
      alternative fragmentation modes of MS/MS, many new de novo sequencing methods
      have been formulated. This paper reviews these recently developed sequencing
      methods including those for alternative MS/MS spectra. The paper first introduces
      background knowledge on peptide sequencing and mass spectrometry, and then
      reviews de novo peptide sequencing methods for traditional CID spectra. After
      that, it focuses on the recent development of de novo methods for alternative
      MS/MS spectra. In addition, methods using multiple spectra from the same peptide
      are surveyed. Finally, conclusions and some directions of future work are
      discussed. 

PMID- 26295162
TI  - Type 2 Diabetes Mellitus Is Associated with Strongyloides stercoralis Treatment
      Failure in Australian Aboriginals.
AB  - OBJECTIVE: To explore the efficacy of ivermectin in the treatment of
      serologically diagnosed cases of Strongyloides stercoralis (S. stercoralis)
      infection in an Aboriginal community and to describe factors that may influence
      the outcome of treatment. METHODS: Longitudinal study of a group of 92
      individuals with serologically diagnosed S. stercoralis treated with ivermectin
      and followed up over a period of approximately 6 months. Main outcomes were
      serological titers pre and post treatment, diabetic status, and duration of
      follow up. FINDINGS: Treatment success was achieved in 62% to 79% of cases
      dependent on the methods employed for the diagnosis of infection and assessment
      of treatment outcome. Type 2 Diabetes Mellitus (T2DM) was found to be
      significantly associated with treatment failure in this group for two of the
      three methods employed. INTERPRETATION: Ivermectin has been confirmed as an
      effective treatment for S stercoralis infection in this setting. T2DM appears to
      be an independent risk factor for treatment failure in this population, and
      plausible mechanisms to explain this observation are presented.

PMID- 26295163
TI  - Castanea sativa (European Chestnut) Leaf Extracts Rich in Ursene and Oleanene
      Derivatives Block Staphylococcus aureus Virulence and Pathogenesis without
      Detectable Resistance.
AB  - The Mediterranean is home to a rich history of medical traditions that have
      developed under the influence of diverse cultures over millennia. Today, many
      such traditions are still alive in the folk medical practices of local people.
      Investigation of botanical folk medicines used in the treatment of skin and soft
      tissue infections led us to study Castanea sativa (European Chestnut) for its
      potential antibacterial activity. Here, we report the quorum sensing inhibitory
      activity of refined and chemically characterized European Chestnut leaf extracts,
      rich in oleanene and ursene derivatives (pentacyclic triterpenes), against all
      Staphylococcus aureus accessory gene regulator (agr) alleles. We present layers
      of evidence of agr blocking activity (IC50 1.56-25 MUg mL-1), as measured in
      toxin outputs, reporter assays hemolytic activity, cytotoxicity studies, and an
      in vivo abscess model. We demonstrate the extract's lack of cytotoxicity to human
      keratinocytes and murine skin, as well as lack of growth inhibitory activity
      against S. aureus and a panel of skin commensals. Lastly, we demonstrate that
      serial passaging of the extract does not result in acquisition of resistance to
      the quorum quenching composition. In conclusion, through disruption of quorum
      sensing in the absence of growth inhibition, this study provides insight into the
      role that non-biocide inhibitors of virulence may play in future antibiotic
      therapies. 

PMID- 26295164
TI  - Stereospecific Inhibitory Effects of CCG-1423 on the Cellular Events Mediated by
      Myocardin-Related Transcription Factor A.
AB  - CCG-1423 suppresses several pathological processes including cancer cell
      migration, tissue fibrosis, and the development of atherosclerotic lesions. These
      suppressions are caused by inhibition of myocardin-related transcription factor A
      (MRTF-A), which is a critical factor for epithelial-mesenchymal transition (EMT).
      CCG-1423 can therefore be a potent inhibitor for EMT. CCG-1423 and related
      compounds, CCG-100602 and CCG-203971 possess similar biological activities.
      Although these compounds are comprised of two stereoisomers, the differences in
      their biological activities remain to be assessed. To address this issue, we
      stereoselectively synthesized optically pure isomers of these compounds and
      validated their biological activities. The S-isomer of CCG-1423 rather than the R
      isomer exhibited modestly but significantly higher inhibitory effects on the
      cellular events triggered by MRTF-A activation including serum response factor
      mediated gene expression and cell migration of fibroblasts and B16F10 melanoma
      cells. Accordingly, the S-isomer of CCG-1423 more potently blocked the serum
      induced nuclear import of MRTF-A than the R-isomer. No such difference was
      observed in cells treated with each of two stereoisomers of CCG-100602 or CCG
      203971. We previously reported that the N-terminal basic domain (NB), which
      functions as a nuclear localization signal of MRTF-A, is a binding site for CCG
      1423. Consistent with the biological activities of two stereoisomers of CCG-1423,
      docking simulation demonstrated that the S-isomer of CCG-1423 was more likely to
      bind to NB than the R-isomer. This is a first report demonstrating the
      stereospecific biological activities of CCG-1423. 

PMID- 26295166
TI  - Characterization of two endoglucanases for the classification of the earthworm,
      Eisenia fetida Waki.
AB  - Eisenia fetida and Eisenia andrei are vermicomposting species that are used as
      model animals for testing chemical material toxicology. Eisenia spp. are grown
      commercially in various fields in Japan. However, these two species have not been
      classified because it is difficult to distinguish them morphologically; thus, all
      bred earthworms are called E. fetida. However, it has been proposed that these
      two species have different expression regulation mechanisms. Here, we classified
      a sample of earthworms purchased from several farms, confirming that both E.
      fetida and E. andrei are present in Japanese earthworm breeding programs. We also
      characterized two highly active endoglucanases (EfEG1 and EfEG2) from the E.
      fetida Waki strain, which contained strong fibrinolytic enzymes for improving
      human health. We confirmed that EfEG1 is 1371 bp long and belongs to GHF9. Thus,
      E. fetida Waki may have commercial application for biomass utilization and as a
      dietary health supplement.

PMID- 26295165
TI  - CsBAFF, a Teleost B Cell Activating Factor, Promotes Pathogen-Induced Innate
      Immunity and Vaccine-Induced Adaptive Immunity.
AB  - B cell activating factor (BAFF) is a member of the tumor necrosis factor family
      that is known to play an important role in B cell activation, proliferation, and
      differentiation in mammals. However, studies of BAFF in teleosts are very limited
      and its function, in particular that under in vivo conditions, is essentially
      unknown. In this study, we conducted in vivo as well as in vitro functional
      analyses of a BAFF homologue (CsBAFF) from the teleost fish tongue sole
      (Cynoglossus semilaevis). CsBAFF is composed of 261 residues and shares moderate
      sequence identities with known BAFFs of other teleosts. CsBAFF expression was
      most abundant in immune organs and was upregulated during bacterial infection.
      Purified recombinant CsBAFF (rCsBAFF) bound to tongue sole lymphocytes and
      promoted cellular proliferation and survival. The results of an in vivo study
      showed that CsBAFF overexpression in tongue sole significantly enhanced
      macrophage activation and reduced bacterial infection in fish tissues, whereas
      knockdown of CsBAFF expression resulted in increased bacterial dissemination and
      colonization in fish tissues. Furthermore, vaccination studies showed that CsBAFF
      enhanced the immunoprotection of a DNA vaccine and augmented the production of
      specific serum antibodies. Taken together, these results provide the first in
      vivo evidence to indicate that teleost BAFF is an immunostimulator that
      significantly contributes to the innate antibacterial immune response and vaccine
      induced adaptive immune response. 

PMID- 26295167
TI  - Group B streptococcal infections in the newborn infant and the potential value of
      maternal vaccination.
AB  - Group B Streptococcus (GBS) is a leading cause of neonatal bacterial infections
      in developed countries. Early-onset disease (EOD) occurs at day 0-6 and late
      onset disease occurs at day 7-89. Currently, the prevention of EOD relies upon
      intrapartum antibiotic prophylaxis (IAP) given to women who are GBS positive at
      prenatal screening or women with risk factors for EOD. Although successfully
      implemented, IAP has not fully eradicated EOD, and incidence rates of late-onset
      disease remain unchanged. Furthermore, antibiotic resistance may result from
      widespread antibiotic use. New prophylactic strategies are therefore of critical
      importance. A vaccine active against GBS, administered during pregnancy and
      combined with targeted IAP, could overcome these problems and reduce the
      mortality and morbidity associated with invasive diseases. 

PMID- 26295168
TI  - Multi-photon transitions and Rabi resonance in continuous wave EPR.
AB  - The study of microwave-radiofrequency multi-photon transitions in continuous wave
      (CW) EPR spectroscopy is extended to a Rabi resonance condition, when the radio
      frequency of the magnetic-field modulation matches the Rabi frequency of a spin
      system in the microwave field. Using the non-secular perturbation theory based on
      the Bogoliubov averaging method, the analytical description of the response of
      the spin system is derived for all modulation frequency harmonics. When the
      modulation frequency exceeds the EPR linewidth, multi-photon transitions result
      in sidebands in absorption EPR spectra measured with phase-sensitive detection at
      any harmonic. The saturation of different-order multi-photon transitions is shown
      to be significantly different and to be sensitive to the Rabi resonance. The
      noticeable frequency shifts of sidebands are found to be the signatures of this
      resonance. The inversion of two-photon lines in some spectral intervals of the
      out-of-phase first-harmonic signal is predicted under passage through the Rabi
      resonance. The inversion indicates the transition from absorption to stimulated
      emission or vice versa, depending on the sideband. The manifestation of the
      primary and secondary Rabi resonance is also demonstrated in the time evolution
      of steady-state EPR signals formed by all harmonics of the modulation frequency.
      Our results provide a theoretical framework for future developments in multi
      photon CW EPR spectroscopy, which can be useful for samples with long spin
      relaxation times and extremely narrow EPR lines. 

PMID- 26295169
TI  - Modeling T(1) and T(2) relaxation in bovine white matter.
AB  - The fundamental basis of T1 and T2 contrast in brain MRI is not well understood;
      recent literature contains conflicting views on the nature of relaxation in white
      matter (WM). We investigated the effects of inversion pulse bandwidth on
      measurements of T1 and T2 in WM. Hybrid inversion-recovery/Carr-Purcell-Meiboom
      Gill experiments with broad or narrow bandwidth inversion pulses were applied to
      bovine WM in vitro. Data were analysed with the commonly used 1D-non-negative
      least squares (NNLS) algorithm, a 2D-NNLS algorithm, and a four-pool model which
      was based upon microscopically distinguishable WM compartments (myelin non
      aqueous protons, myelin water, non-myelin non-aqueous protons and
      intra/extracellular water) and incorporated magnetization exchange between
      adjacent compartments. 1D-NNLS showed that different T2 components had different
      T1 behaviours and yielded dissimilar results for the two inversion conditions. 2D
      NNLS revealed significantly more complicated T1/T2 distributions for narrow
      bandwidth than for broad bandwidth inversion pulses. The four-pool model fits
      allow physical interpretation of the parameters, fit better than the NNLS
      techniques, and fits results from both inversion conditions using the same
      parameters. The results demonstrate that exchange cannot be neglected when
      analysing experimental inversion recovery data from WM, in part because it can
      introduce exponential components having negative amplitude coefficients that
      cannot be correctly modeled with nonnegative fitting techniques. While assignment
      of an individual T1 to one particular pool is not possible, the results suggest
      that under carefully controlled experimental conditions the amplitude of an
      apparent short T1 component might be used to quantify myelin water. 

PMID- 26295170
TI  - Development of a superconducting bulk magnet for NMR and MRI.
AB  - A superconducting bulk magnet composed of six vertically stacked annular single
      domain c-axis-oriented Eu-Ba-Cu-O crystals was energized to 4.74 T using a
      conventional superconducting magnet for high-resolution NMR spectroscopy. Shim
      coils, gradient coils, and radio frequency coils for high resolution NMR and MRI
      were installed in the 23 mm-diameter room-temperature bore of the bulk magnet. A
      6.9 ppm peak-to-peak homogeneous region suitable for MRI was achieved in the
      central cylindrical region (6.2 mm diameter, 9.1 mm length) of the bulk magnet by
      using a single layer shim coil. A 21 Hz spectral resolution that can be used for
      high resolution NMR spectroscopy was obtained in the central cylindrical region
      (1.3 mm diameter, 4 mm length) of the bulk magnet by using a multichannel shim
      coil. A clear 3D MR image dataset of a chemically fixed mouse fetus with (50
      MUm)(3) voxel resolution was obtained in 5.5 h. We therefore concluded that the
      cryogen-free superconducting bulk magnet developed in this study is useful for
      high-resolution desktop NMR, MRI and mobile NMR device.

PMID- 26295171
TI  - Applications of zero-valent silicon nanostructures in biomedicine.
AB  - Zero-valent, or elemental, silicon nanostructures exhibit a number of properties
      that render them attractive for applications in nanomedicine. These materials
      hold significant promise for improving existing diagnostic and therapeutic
      techniques. This review summarizes some of the essential aspects of the
      fabrication techniques used to generate these fascinating nanostructures,
      comparing their material properties and suitability for biomedical applications.
      We examine the literature in regards to toxicity, biocompatibility and
      biodistribution of silicon nanoparticles, nanowires and nanotubes, with an
      emphasis on surface modification and its influence on cell adhesion and
      endocytosis. In the final part of this review, our attention is focused on
      current applications of the fabricated silicon nanostructures in nanomedicine,
      specifically examining drug and gene delivery, bioimaging and biosensing. 

PMID- 26295172
TI  - Taking the ruler to the jungle: single-molecule FRET for understanding
      biomolecular structure and dynamics in live cells.
AB  - Single-molecule Forster resonance energy transfer (smFRET) serves as a molecular
      ruler that is ideally posed to study static and dynamic heterogeneity in living
      cells. Observing smFRET in cells requires appropriately integrated labeling,
      internalization and imaging strategies, and significant progress has been made
      towards that goal. Pioneering studies have demonstrated smFRET detection in both
      prokaryotic and eukaryotic systems, using both wide-field and confocal
      microscopies, and have started to answer exciting biological questions. We
      anticipate that future technical developments will open the door to smFRET for
      the study of structure, conformational changes and kinetics of biomolecules in
      living cells. 

PMID- 26295173
TI  - Design and synthesis of 4-benzyl-1-(2H)-phthalazinone derivatives as novel
      androgen receptor antagonists.
AB  - The androgen receptor (AR) plays important roles in multiple physiological
      functions, including differentiation, growth, and maintenance of male
      reproductive organs, and also has effects on hair and skin. In this paper, we
      report the synthesis of nonsteroidal AR antagonists having a 4-benzyl-1-(2H)
      phthalazinone skeleton. Among the synthesized compounds, 11c with two ortho
      substituents on the phenyl group potently inhibited SC-3 cell proliferation
      (IC50: 0.18 MUM) and showed high wt AR-binding affinity (IC50: 10.9 MUM),
      comparable to that of hydroxyflutamide (3). Compound 11c also inhibited
      proliferation of LNCaP cells containing T877A-mutated AR. Docking study of 11c
      with the AR ligand-binding domain indicated that the benzyl group is important
      for the antagonism. These phthalazinone derivatives may be useful for
      investigating potential clinical applications of AR antagonists.

PMID- 26295174
TI  - Exploring the 3-piperidin-4-yl-1H-indole scaffold as a novel antimalarial
      chemotype.
AB  - A series of 3-piperidin-4-yl-1H-indoles with building block diversity was
      synthesized based on a hit derived from an HTS whole-cell screen against
      Plasmodium falciparum. Thirty-eight compounds were obtained following a three
      step synthetic approach and evaluated for anti-parasitic activity. The SAR shows
      that 3-piperidin-4-yl-1H-indole is intolerant to most N-piperidinyl
      modifications. Nevertheless, we were able to identify a new compound (10d) with
      lead-like properties (MW = 305; cLogP = 2.42), showing antimalarial activity
      against drug-resistant and sensitive strains (EC50 values ~ 3 MUM), selectivity
      for malaria parasite and no cross-resistance with chloroquine, thus representing
      a potential new chemotype for further optimization towards novel and affordable
      antimalarial drugs.

PMID- 26295175
TI  - Pyrazolo[3,4-h]quinolines promising photosensitizing agents in the treatment of
      cancer.
AB  - A new series of pyrazolo[3,4-h]quinolines, heteroanalogues of angelicin was
      conveniently prepared with a broad substitution pattern. A large number of
      derivatives was obtained and the cellular photocytotoxicity was evaluated in
      vitro against 5 different human tumor cell lines with GI50 values reaching the
      nanomolar level (14.52-0.04 MUM). Selected compounds were able to photoinduce a
      massive cell death with the involvement of mitochondria. Their photodamage
      cellular targets were proteins and lipids and they did not cause any kind of DNA
      photodamage. This latter event is of considerable importance in the modulation of
      long term side effects, generally associated with the use of classical
      furocoumarins.

PMID- 26295176
TI  - Effect of nutritional counseling on low-density lipoprotein cholesterol among
      Thai HIV-infected adults receiving antiretroviral therapy.
AB  - HIV-infected patients receiving antiretroviral therapy have increased risk of
      metabolic syndrome, including dyslipidemia. In this study, we determined whether
      individual nutritional counseling reduced dyslipidemia, particularly low-density
      lipoprotein (LDL) cholesterol, among HIV-infected patients with dyslipidemia not
      currently taking lipid-lowering medication. We conducted a randomized 24-week
      trial among HIV-infected patients with dyslipidemia who were on antiretroviral
      therapy and were eligible to initiate therapeutic lifestyle changes according to
      the Thai National Cholesterol Education Program. Participants were randomly
      assigned to an intervention group that received individual counseling with a
      nutritionist for seven sessions (baseline, weeks 2, 4, 8, 12, 18, and 24) and a
      control group that received standard verbal diet information at baseline and
      nutritional counseling only at week 24. A 24-h recall technique was used to
      assess dietary intake for both groups at baseline and week 24. Lipid profile
      (total cholesterol, LDL, high-density lipoprotein (HDL), and triglyceride) was
      measured at baseline and after 12 and 24 weeks of therapy. An intention-to-treat
      and linear mixed model were used. Seventy-two patients were randomly assigned,
      and 62 (86%) participants completed their lipid profile test. After 12 weeks of
      follow-up, there were significant reductions in the intervention group for total
      cholesterol (-14.4 +/- 4.6 mg/dL, P = .002), LDL cholesterol (-13.7 +/- 4.1
      mg/dL, P = .001), and triglyceride (-30.4 +/- 13.8 mg/dL, P = .03). A significant
      reduction in LDL cholesterol was also observed in the control group (-7.7 +/- 3.8
      mg/dL, P = .04), but there were no significant differences in change of mean
      lipid levels between the groups at 12 weeks of follow-up. After 24 weeks,
      participants assigned to the intervention group demonstrated significantly
      greater decreases in serum total cholesterol (-19.0 +/- 4.6 vs. 0.2 +/- 4.3
      mg/dL, P = .003) and LDL cholesterol (-21.5 +/- 4.1 vs. -6.8 +/- 3.8 mg/dL, P =
      .009). There were no significant changes in HDL cholesterol or triglyceride
      levels in either group.

PMID- 26295177
TI  - Ex vivo Raman spectroscopic study of breast metastatic lesions in lungs in animal
      models.
AB  - The lung is one of the most common sites of metastases, with approximately 50% of
      patients with extrathoracic cancer exhibiting pulmonary metastases. Correct
      identification of the metastatic status of a lung lesion is vital to therapeutic
      planning and better prognosis. However, currently available diagnostic
      techniques, such as conventional radiography and low dose computed tomography
      (LDCT), may fail to identify metastatic lesions. Alternative techniques such as
      Raman spectroscopy (RS) are hence being extensively explored for correct
      diagnosis of metastasis. The current ex vivo study aims to evaluate the ability
      of a fiber optic-based Raman system to distinguish breast cancer metastasis in
      lung from primary breast and lung tumor in animal models. In this study, spectra
      were acquired from normal breast, primary breast tumor, normal lung, primary lung
      tumor, and breast cancer metastasis in lung tissues and analyzed using principal
      component analysis and principal component-linear discriminant analysis. Breast
      cancer metastasis in lung could be classified with 71% classification efficiency.
      Approximately 6% breast metastasis spectra were misclassified with breast tumor,
      probably due to the presence of breast cancer cells in metastasized lungs. Test
      prediction results show 64% correct prediction of breast metastasis, while 13%
      breast metastasis spectra were wrongly predicted as breast tumor, suggesting the
      possible influence of breast cancer cells. Thus, findings of this study, the
      first of such explorations, demonstrate the potential of RS in classifying breast
      metastasis in lungs from primary lung and primary breast tumor. Prospective
      evaluation on a larger cohort with better multivariate analysis, combined with
      LDCT and recently developed real-time in vivo probes, RS can play a significant
      role in nonsurgical screening of lesions, which can lead to individualized
      therapeutic regimes and improved prognoses.

PMID- 26295179
TI  - Liver Transplant for Cholangiocarcinoma: A Comeback?
AB  - Liver transplant is not a standard therapy for cholangiocarcinoma; complete
      surgical resection of the tumor is currently the treatment of choice. Palliative
      options offer only short-term survival. After initial recurrence rates after
      liver transplant for cholangiocarcinoma in the 1990s were unacceptably high,
      cholangiocarcinoma has been regarded widely as a contraindication to liver
      transplant. Ubiquitous organ shortage further supports this conviction. Careful
      patient selection and a rigorous perioperative treatment by radiochemotherapy
      have produced some impressive survival data in specialized transplant centers in
      recent years. Although the graft shortage is aggravating in the Western world,
      the issue of liver transplant as a treatment for irresectable cholangiocarcinoma
      is being discussed. This review article provides an update and overview on the
      current status of liver transplant as a potential option for patients with
      irresectable cholangiocarcinoma. 

PMID- 26295178
TI  - Auditory nerve impulses induced by 980 nm laser.
AB  - The discovery that a pulsed laser could trigger an auditory neural response
      inspired ongoing research on cochlear implants activated by optical stimulus
      rather than by electrical current. However, most studies to date have used
      visible light (532 nm) or long-wavelength near-infrared (>1840  nm ) and involved
      making a hole in the cochlea. This paper investigates the effect of optical
      parameters on the optically evoked compound action potentials (oCAPs) from the
      guinea pig cochlea, using a pulsed semiconductor near-infrared laser (980 nm)
      without making a hole in the cochlea. Synchronous trigger laser pulses were used
      to stimulate the cochlea, before and after deafening, upon varying the pulse
      duration (30-1000  MUs ) and an amount of radiant energy (0-53.2  mJ/cm 2 ).
      oCAPs were successfully recorded after deafening. The amplitude of the oCAPs
      increased as the infrared radiant energy was increased at a fixed 50  MUs pulse
      duration, and decreased with a longer pulse duration at a fixed 37.1  mJ/cm 2
      radiant energy. The latency of the oCAPs shortened with increasing radiant energy
      at a fixed pulse duration. With a higher stimulation rate, the amplitude of the
      oCAPs' amplitude decreased.

PMID- 26295180
TI  - Factors Affecting the Occurrence of Spinal Reflexes in Brain Dead Cases.
AB  - OBJECTIVES: Brain death is defined as the permanent absence of all cortical and
      brain stem reflexes. A wide range of spontaneous or reflex movements that are
      considered medullary reflexes are observed in heart beating cases that appear
      brain dead, which may create uncertainty about the diagnosis of brain death and
      cause delays in deceased-donor organ donation process. We determined the
      frequency and type of medullary reflexes and factors affecting their occurrence
      in brain dead cases. MATERIALS AND METHODS: During 1 year, 122 cases who
      fulfilled the criteria for brain death were admitted to the special intensive
      care unit for organ procurement of Masih Daneshvari Hospital. Presence of spinal
      reflexes was evaluated by trained coordinators and was recorded in a form in
      addition to other information including demographic characteristics, cause of
      brain death, time from detection of brain death, history of craniotomy, vital
      signs, serum electrolyte levels, and parameters of arterial blood gas
      determination. RESULTS: Most cases (63%) included in this study were male, and
      mean age was 33 +/- 15 y. There was > 1 spinal reflex observed in 40 cases (33%).
      The most frequent reflex was plantar response (17%) following by myoclonus (10%),
      triple flexion reflex (9%), pronator extension reflex (8%), and undulating toe
      reflex (7%). Mean systolic blood pressure was significantly higher in cases who
      exhibited medullary reflexes than other cases (126 +/- 19 mm Hg vs 116 +/- 17 mm
      Hg; P = .007). CONCLUSIONS: Spinal reflexes occur frequently in brain dead cases,
      especially when they become hemodynamically stable after treatment in the organ
      procurement unit. Observing these movements by caregivers and family members has
      a negative effect on obtaining family consent and organ donation. Increasing
      awareness about spinal reflexes is necessary to avoid suspicion about the brain
      death diagnosis and delays in organ donation.

PMID- 26295181
TI  - De Novo Visceral Malignancies in Renal Transplant Recipients: A Single Center
      Experience of 2054 Recipients for More Than 30 Years.
AB  - OBJECTIVES: We report the incidence and pattern of malignancies in renal
      transplant recipients from our department. MATERIALS AND METHODS: Between March
      1983 and August 2013, the records of 2054 renal transplant recipients from our
      department were retrospectively reviewed with regard to type of neoplasm, age,
      gender, interval between the transplant and the diagnosis of malignancy,
      immunosuppressive regimens, graft functional status, and rejection episodes.
      RESULTS: Among the 2054 renal transplant recipients, visceral malignancies
      developed in 74 patients (3.6%). The mean age at transplant was 43.9 years, and
      the mean age at death was 61.9 years. Sixty-eight patients (91.9%) died with a
      functioning graft. Fifty-four (73%) died during follow-up. The mean time from
      transplant to malignancy was 96.4 months, and from malignancy to death was 27.5
      months. No difference regarding the type of immunosuppression, the type of donor,
      or the interval between transplant and malignancy was detected when we compared
      cancers. CONCLUSIONS: Malignancies after a renal transplant display aggressive
      behavior and occur more frequently several years after the transplant, but they
      also may occur earlier. The type of immunosuppression, the type of donor, or the
      interval between transplant and malignancy do not differ significantly among
      cancers.

PMID- 26295182
TI  - Apelin and New-Onset Diabetes After Transplant in Living Kidney Allograft
      Recipients.
AB  - OBJECTIVES: Apelin, a cytokine mainly secreted by adipocytes and several tissues,
      includes the gastrointestinal tract, adipose, brain, kidney, liver, lung, and
      various sites within the cardiovascular system. Apelin is closely related to
      glucose metabolism, and has been proposed to be a promising therapeutic agent in
      treating insulin resistance. Apelin and orphaned G-protein-coupled apelin exhibit
      roles in regulating fluid homeostasis. Circulating serum apelin suppresses
      insulin secretion by binding to the G-protein-coupled apelin receptor on B cells
      of islets of Langerhans. Several studies also have documented the altered level
      of serum apelin in type 2 diabetic patients, but the results remain
      controversial. This study sought to analyze apelin levels in new-onset diabetes
      after transplant. MATERIALS AND METHODS: Forty-seven diabetic renal transplant
      recipients were compared with 40 nondiabetic renal transplant recipients. Data
      were collected for positive family history of diabetes, body weight, body mass
      index, blood pressure, and blood chemistry including apelin level. Logistic
      multiple analysis were made for statistically significant data on univariate
      analysis. RESULTS: Apelin levels were significantly higher among obese,
      hypercholesterolemia new-onset diabetes after transplant patients, 428.7 +/-
      193.29, 256.8 +/- 128 (P > .001). There was appositive correlation between serum
      apelin and proteinuria. CONCLUSIONS: Serum apelin has a high level in new-onset
      diabetes after transplant, than nondiabetic patients, and they positively
      correlate with proteuria in new-onset diabetes after transplant patients.

PMID- 26295183
TI  - Tumor Characteristics and Long-Term Outcome of Incidental Hepatocellular
      Carcinoma After Orthotopic Liver Transplant.
AB  - OBJECTIVES: Orthotopic liver transplant is the treatment of choice for
      hepatocellular carcinoma in cirrhotic patients with satisfactory oncologic and
      survival outcomes. Incidental hepatocellular carcinoma is frequently a reported
      finding in the explant pathology after orthotopic liver transplant. MATERIAL AND
      METHODS: The present study retrospectively analyzed the tumor characteristics and
      outcomes of 50 incidental hepatocellular carcinomas compared with 252 transplants
      for known hepatocellular carcinoma. RESULTS: Patients with incidental
      hepatocellular carcinoma had lower peak alpha-fetoprotein level (P = .001), lower
      pretransplant alpha-fetoprotein level (P = .002), smaller total tumor size (P =
      .0001), fewer tumor numbers (P = .0001), lower level of microvascular invasion (P
      = .001), more cases within Milan criteria (P = .005), and more well
      differentiated tumors (P = .017). However, no difference in survival rates was
      observed between the 2 groups. In 35 patients (70%) who had incidental
      hepatocellular carcinoma, pretransplant imaging studies were normal;
      ultrasonography was used as the only screening tool in 25 of 35 patients (71%)
      who had incidental hepatocellular carcinoma, and 15 patients (30%) who had
      incidental hepatocellular carcinoma had regenerative or dysplastic nodules. The
      accuracy of ultrasonography in our unit for diagnosing hepatocellular carcinoma
      was 97.5%. A quarter of hepatitis B recipients had incidental hepatocellular
      carcinoma with a younger median recipient age. Tumor recurrence was higher with
      incidental hepatocellular carcinoma in hepatitis C recipients (22%). However, the
      overall recurrence was similar between all hepatitis and nonhepatitis recipients
      who were transplanted for incidental or known hepatocellular carcinoma.
      CONCLUSIONS: Incidental hepatocellular carcinoma has similar outcome as known
      hepatocellular carcinoma. Early screening of hepatitis B patients is recommended,
      and cross-sectional imaging is not mandatory for hepatocellular carcinoma
      screening in patients who are on the waiting list.

PMID- 26295184
TI  - Morphologic and Functional Study of Heterotopic Splenic Tissue Allografts in
      Rabbits.
AB  - OBJECTIVES: To assess the viability and induction of immunotolerance of
      nonvascularized splenic alloimplants. The phagocytic functions of splenic
      implants also were studied. MATERIALS AND METHODS: Thirty-six adult female New
      Zealand and California rabbits were used, and these animals were divided into the
      following 5 groups: (n = 6 / groups 1-4) group 1 (sham operations); group 2
      (total splenectomy); group 3 (implantation of autologous sliced splenic tissue in
      the greater omentum following splenectomy); group 4 (implantation of allogenic
      sliced splenic tissue in the greater omentum after splenectomy); and group 5 (n =
      12) (implanting allogenic sliced splenic tissue in the greater omentum after
      splenectomy and receiving oral cyclosporine at a dosage of 40 mg/kg/d). All
      animals were followed for 120 days after the operations, then received venous
      injections of China ink (groups 1, 2, 3, 4, 5A) or a colloidal
      radiopharmaceutical (group 5B), and subsequently underwent reoperations.
      Hematimetric examinations were performed, and the histologic aspects and
      phagocytic functions of the implants were assessed. RESULTS: Spontaneous
      immunotolerance was not induced by sliced splenic allografts implanted in the
      greater omentum. The use of cyclosporine did not preserve the viabilities of the
      implants. All animals in group 3, which were subjected to autologous implants,
      exhibited viable implants that exhibited phagocytic function, although this
      phagocytic function was reduced compared with that of the normal spleen.
      CONCLUSIONS: No viable spleen alloimplants were observed regardless of the
      presence of cyclosporine. Spontaneous immunotolerance was not induced by sliced
      splenic alloimplants.

PMID- 26295185
TI  - Descemet Membrane Endothelial Keratoplasty as a Secondary Approach After Failure
      of Penetrating Keratoplasty.
AB  - OBJECTIVES: To investigate visual outcome and postoperative complications in
      patients undergoing Descemet membrane endothelial keratoplasty with graft failure
      after penetrating keratoplasty. MATERIALS AND METHODS: A retrospective analysis
      was performed with 5 patients who underwent Descemet membrane endothelial
      keratoplasty after failed penetrating keratoplasty. Intraoperative and
      postoperative complications were recorded. Visual acuity, rehabilitation phase,
      refraction stability, central corneal thickness, endothelial cell count, possible
      immunologic reactions, and optical coherence tomography of the anterior eye
      segment were evaluated. A subjective questionnaire was used to evaluate patient
      satisfaction. RESULTS: There were no intraoperative complications. All patients
      had graft detachment, which made air injection necessary. In all cases, visual
      acuity significantly increased (medium visual acuity [logarithm of the minimum
      angle of resolution]: 0.68 +/- 0.31 logarithm of the minimum angle of resolution
      after 4 weeks and 0.35 +/- 0.37 after 6 months; P = .043), refraction was stable,
      corneal thickness was reduced (average, 514 +/- 11 MUm), and endothelial cell
      count was reduced (average, 1398 +/- 510 cells/mm(2)) after 6 months, which
      corresponds with a medium loss 40%. In the questionnaire, visual outcome,
      estimated time for recovery, and rehabilitation and patient satisfaction were
      better after Descemet membrane endothelial keratoplasty than penetrating
      keratoplasty. No postoperative elevation of pressure, development of pupillary
      block, or graft rejection, and no peripheral anterior synechiae or other
      abnormalities were observed with optical coherence tomography during the first 6
      postoperative months. CONCLUSIONS: Descemet membrane endothelial keratoplasty is
      a suitable technique for the treatment of graft failure after penetrating
      keratoplasty and helped our patients rapidly achieve good visual acuity, with
      reduction of postoperative complications, but the visual outcome might be
      limited.

PMID- 26295186
TI  - A Generalizable Platform for the Photoactivation of Cell Surface Receptors.
AB  - Polarized signal transduction from cell surface receptors plays a central role in
      the development and homeostasis of multicellular organisms, and it also
      contributes to cellular dysfunction in many disease states. Understanding the
      molecular and cellular bases of polarized signaling requires experimental methods
      that provide precise spatiotemporal control of receptor activation. However, we
      currently lack strategies for inducing both sustained and spatially constrained
      signal transduction. In the present study, we combined synthetic and cell
      biological tools to develop a generalizable photoactivation approach for the
      stimulation of cell surface receptors. Our system, which is based upon the local
      decaging of a "universal" peptide ligand, is particularly well suited for the
      live imaging of single cells. We anticipate that it will greatly facilitate
      future mechanistic analyses of polarized signal transduction in a variety of cell
      types. 

PMID- 26295187
TI  - Shape and Effective Spring Constant of Liquid Interfaces Probed at the Nanometer
      Scale: Finite Size Effects.
AB  - We investigate the shape and mechanical properties of liquid interfaces down to
      nanometer scale by atomic force microscopy (AFM) and scanning electron microscopy
      (SEM) combined with in situ micromanipulation techniques. In both cases, the
      interface is probed with a cylindrical nanofiber with radius R of the order of 25
      100 nm. The effective spring constant of the nanomeniscus oscillated around its
      equilibrium position is determined by static and frequency-modulation (FM) AFM
      modes. In the case of an unbounded meniscus, we find that the effective spring
      constant k is proportional to the surface tension gamma of the liquid through k =
      (0.51 +/- 0.06)gamma, regardless of the excitation frequency from quasi-static up
      to 450 kHz. A model based on the equilibrium shape of the meniscus reproduces
      well the experimental data. Electron microscopy allowed to visualize the meniscus
      profile around the fiber with a lateral resolution of the order of 10 nm and
      confirmed its catenary shape. The influence of a lateral confinement of the
      interface is also investigated. We showed that the lateral extension L of the
      meniscus influences the effective spring constant following a logarithmic
      evolution k ~ 2pigamma/ln(L/R) deduced from the model. This comprehensive study
      of liquid interface properties over more than 4 orders of magnitude in meniscus
      size shows that advanced FM-AFM and SEM techniques are promising tools for the
      investigation of mechanical properties of liquids down to nanometer scale. 

PMID- 26295188
TI  - Automatic Segmentation of the Corpus Callosum Using a Cell-Competition Algorithm:
      Diffusion Tensor Imaging-Based Evaluation of Callosal Atrophy and Tissue
      Alterations in Patients With Systemic Lupus Erythematosus.
AB  - OBJECTIVE: Patients with neuropsychiatric systemic lupus erythematosus (NPSLE)
      may exhibit corpus callosal atrophy and tissue alterations. Measuring the
      callosal volume and tissue integrity using diffusion tensor imaging (DTI) could
      help to differentiate patients with NPSLE from patients without NPSLE. Hence,
      this study aimed to use an automatic cell-competition algorithm to segment the
      corpus callosum and to investigate the effects of central nervous system (CNS)
      involvement on the callosal volume and tissue integrity in patients with SLE.
      METHODS: Twenty-two SLE patients with (N = 10, NPSLE) and without (N = 12, non
      NPSLE) CNS involvement and 22 control subjects were enrolled in this study. For
      volumetric measurement, a cell-competition algorithm was used to automatically
      delineate corpus callosal boundaries based on a midsagittal fractional anisotropy
      (FA) map. After obtaining corpus callosal boundaries for all subjects, the
      volume, FA, and mean diffusivity (MD) of the corpus callosum were calculated. A
      post hoc Tamhane's T2 analysis was performed to statistically compare differences
      among NPSLE, non-NPSLE, and control subjects. A receiver operating characteristic
      curve analysis was also performed to compare the performance of the volume, FA,
      and MD of the corpus callosum in differentiating NPSLE from other subjects.
      RESULTS: Patients with NPSLE had significant decreases in volume and FA but an
      increase in MD in the corpus callosum compared with control subjects, whereas no
      significant difference was noted between patients without NPSLE and control
      subjects. The FA was found to have better performance in differentiating NPSLE
      from other subjects. CONCLUSIONS: A cell-competition algorithm could be used to
      automatically evaluate callosal atrophy and tissue alterations. Assessments of
      the corpus callosal volume and tissue integrity helped to demonstrate the effects
      of CNS involvement in patients with SLE.

PMID- 26295190
TI  - The Combination of Diffusion- and T2-Weighted Imaging in Predicting Deep
      Myometrial Invasion of Endometrial Cancer: A Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: The aim of this study was to explore the diagnostic difference among
      the combination of diffusion-weighted imaging (DWI) and T2-weighted imaging
      (T2WI), diffusion-weighted imaging (DWI), and dynamic contrast-enhanced (DCE)
      magnetic resonance imaging (MRI) in predicting deep myometrial invasion of
      endometrial cancer. METHODS: A structured search was conducted to identify
      published studies between January 2005 and April 2014, which assessed depth of
      myometrial invasion in endometrial cancer by using DCE-MRI or DWI or DWI-T2WI.
      RESULTS: A total of 15 studies were included. Significant difference was found
      between DWI-T2WI and DWI in pooled specificity, and also in comparison between
      DCE-MRI and DWI-T2WI (P < 0.05). In summary, receiver operating characteristic
      analysis, area under the curve for DWI-T2WI, DWI, and DCE-MRI were 0.94, 0.90,
      and 0.93, respectively. CONCLUSIONS: Diffusion-weighted imaging-T2WI can improve
      diagnostic performance in comparison with DWI alone. Meanwhile, DWI-T2WI performs
      better than DCE-MRI in predicting myometrial invasion of endometrial cancer. It
      may be an alternative for DCE-MRI in presurgical staging of endometrial cancer.

PMID- 26295189
TI  - Effect of Right-Sided Versus Left-Sided Contrast Injection on Intra-arterial
      Opacification Characteristics of Head and Neck Computed Tomography Angiograms and
      Interactions With Patient Sex, Weight, and Cardiac Output.
AB  - OBJECTIVE: The aims of this study were to support the standard clinical
      assumption that preferential right-sided injection (RSI) over left-sided
      injection (LSI) results in improved head and neck computed tomography angiograms
      and to determine which patients most benefit from RSIs. METHODS: Head and neck
      computed tomography angiograms of 453 RSIs and 419 LSIs were included.
      Interactions between injection side, age, weight, body mass index, and left
      ventricular ejection fraction with mean vessel Hounsfield units (HU) were
      compared. Statistical analysis was performed using 2-tailed Student t tests, Mann
      Whitney U tests, and simple linear (SL) and multiple linear regressions. RESULTS:
      Right-sided injection yielded higher HU for patients older than 40 years (eg, RSI
      of the right common carotid artery [RCCA] vs LSI of the RCCA; P < 0.01). Body
      mass index (eg, RCCA; r = -0.31, P < 0.01 [SL]) and weight (eg, RCCA; r = -0.39,
      P < 0.01 [SL]) were negatively correlated with HU. Female had higher HU (mean +/-
      SE, +39.7 +/- 7.6 HU; P < 0.01 [multiple linear]). Left ventricular ejection
      fraction had no interactions with injection side or HU. CONCLUSIONS: The findings
      support preferential RSI in patients older than 40 years with higher body mass
      index and weight, particularly male.

PMID- 26295191
TI  - Material Decomposition in Dual-Energy Computed Tomography Separates High-Z
      Elements From Iodine, Identifying Potential Contrast Media Tailored for Dual
      Contrast Medium Examinations.
AB  - OBJECTIVE: The aim of this study was to determine the potential of different high
      Z elements to act as contrast media (CMs) alongside iodine (I) in dual-CM, dual
      energy (DE) computed tomography examinations. METHODS: Gadolinium (Gd), tantalum
      (Ta), wolfram (W), gold (Au), and bismuth (Bi) in addition to I were examined at
      all available kilovolt settings in a DE computed tomography scanner. Dual-energy
      ratios were calculated by dividing attenuation at low kilovolt by attenuation at
      high kilovolt. Dual-energy data sets were loaded into material decomposition
      software to evaluate separation of the elements from I. RESULTS: The DE ratios of
      Ta, W, and Au ranged between 0.9 and 1.2, being considerably lower than I at 1.9
      to 2.6. These elements were completely separated from I using material
      decomposition. Gadolinium and Bi were more similar to I at 1.4 to 1.9. However,
      separation was nearly complete for Bi and suboptimal for Gd. CONCLUSIONS:
      Tantalum, W, and Au are ideal candidates for dual-CM examinations, whereas Bi is
      a slightly weaker candidate.

PMID- 26295192
TI  - Quantitative and Qualitative Comparison of Single-Source Dual-Energy Computed
      Tomography and 120-kVp Computed Tomography for the Assessment of Pancreatic
      Ductal Adenocarcinoma.
AB  - PURPOSE: The aim of this study was to compare contrast-to-noise ratio (CNR) and
      signal-to-noise ratio (SNR) between pancreatic-phase dual-energy computed
      tomography (DECT) and 120-kVp CT for pancreatic ductal adenocarcinoma (PDA).
      MATERIALS AND METHODS: Seventy-eight patients underwent multiphasic pancreatic
      imaging protocols for PDA (40, DECT; 38, 120-kVp CT [control]). Using pancreatic
      phase, CNR and SNR for PDA were obtained for DECT at monochromatic energies 50
      through 80 keV, iodine material density images, and 120-kVp images. Using a 5
      point scale (1, excellent; 5, markedly limited), images were qualitatively
      assessed by 2 radiologists in consensus for PDA detection, extension, vascular
      involvement, and noise. Wilcoxon signed rank and 2-sample tests were used to
      compare the qualitative measures, CNR and SNR, for DECT and 120-kVp images.
      Bonferroni correction was applied. RESULTS: Iodine material density image had
      significantly higher CNR and SNR for PDA than any monochromatic energy images (P
      < 0.0001) and the 120-kVp images. Qualitatively, 70-keV images were rated highest
      in the categories of tumor extension and vascular invasion and were similar to
      120-kVp images. CONCLUSIONS: Our results indicate that DECT improves PDA lesion
      conspicuity compared with routine 120-kVp CT, which may allow for better
      detection of PDA.

PMID- 26295193
TI  - A Comparison of Different Methods to Generate Tooth Surface Models Without
      Applying Ionizing Radiation for Digital 3-Dimensional Image Fusion With Magnetic
      Resonance Imaging-Based Data of the Head and Neck Region.
AB  - OBJECTIVE: The 3-dimensional display of the vocal tract and teeth is necessary in
      numerous clinical and scientific contexts. Due to the different tissue properties
      this can only be achieved by combining different imaging techniques. A comparison
      of methods to record the tooth surface to create combined models of the vocal
      tract and teeth without applying ionizing radiation is displayed in this study.
      METHODS: Four methods to record the tooth surface were compared concerning their
      clinical accuracy after combination with magnetic resonance imaging (MRI)-based
      vocal tract models. With 2 of the presented methods the information of the tooth
      surface was obtained from MRI data. With the other 2 methods, the tooth surface
      was captured using a digital and a conventional impression technique. RESULTS:
      Impression techniques received the best rating results. CONCLUSIONS: The digital
      3-dimensional image fusion of dental impression and MRI resulted in a virtual
      model of the vocal tract and teeth with a high clinical accuracy without applying
      ionizing radiation.

PMID- 26295194
TI  - Assessment of Left Ventricular Enlargement at Multidetector Computed Tomography.
AB  - PURPOSE: Because left ventricular (LV) enlargement (LVE) is indicative of an
      array of cardiac pathologies, including cardiomyopathic, ischemic, and valvular
      heart diseases, it is important to recognize it early in the course of these
      diseases. The recognition of LVE on nongated contrast-enhanced computed
      tomography (CT) scans should be facilitated by the availability of a dimensional
      index. To our knowledge, no CT index of LVE has been proposed. Therefore, the
      study aimed to define whether the maximum LV diameter (LVd) measured on nongated
      multidetector computed tomography can identify LVE when referencing
      echocardiography as the diagnostic standard. MATERIALS AND METHODS: The patient
      population consisted of 438 consecutive patients who had a contrast-enhanced,
      nongated 16- or 64-detector CT of the chest for evaluation of pulmonary embolism
      or aortic dissection between January 2006 and March 2008. One hundred fifty-five
      patients in this group also had an echocardiogram within 2 months of the CT
      study. The maximum LV cavity size, septal to lateral wall dimension, was measured
      perpendicularly to the long axis of the left ventricle on the axial CT scans by 2
      observers blinded to the echocardiography data.An receiver operating
      characteristic analysis was performed to identify a highly specific cutoff for
      the diagnosis of LVE on CT, using echocardiogram as the standard of reference.
      Interobserver agreement was assessed using Bland-Altman analysis. RESULTS: A
      total of 84 females and 71 males were evaluated (female to male ratio of 1.09).
      The mean age for the 155 patients was 58 years. Six percent of these patients had
      a diagnosis of LVE on 2-dimensional echocardiography. The mean (SEM) LV internal
      diameter at nongated multidetector computed tomography between the group with
      normal LV and the group with LVE by echocardiography was 4.4 (0.7) cm for the
      normal LV and 5.9 (1.2) cm for the dilated LVs (P < 0.0001). With the use of
      threshold value of LVd of 5.6 cm, a sensitivity of 78%, specificity of 100%,
      positive likelihood ratio of 113.5, and negative likelihood ratio of 0.22 were
      calculated. The LVd measurements had an excellent agreement between observers on
      the Bland-Altman analysis. CONCLUSIONS: Left ventricular enlargement can be
      reliably identified on nongated contrast-enhanced multidetector CT when the
      maximum luminal diameter of the LV is greater than 5.6 cm. Nongated contrast
      enhanced CT scan can be used to recognize LVE.

PMID- 26295195
TI  - Adsorption of dyes by ACs prepared from waste tyre reinforcing fibre. Effect of
      texture, surface chemistry and pH.
AB  - This paper compares the importance of the texture and surface chemistry of waste
      tyre activated carbons in the adsorption of commercial dyes. The adsorption of
      two commercial dyes, Basic Astrazon Yellow 7GLL and Reactive Rifafix Red 3BN on
      activated carbons made up of reinforcing fibres from tyre waste and low-rank
      bituminous coal was studied. The surface chemistry of activated carbons was
      modified by means of HCl-HNO3 treatment in order to increase the number of
      functional groups. Moreover, the influence of the pH on the process was also
      studied, this factor being of great importance due to the amphoteric
      characteristics of activated carbons. The activated carbons made with reinforcing
      fibre and coal had the highest SBET, but the reinforcing fibre activated carbon
      samples had the highest mesopore volume. The texture of the activated carbons was
      not modified upon acid oxidation treatment, unlike their surface chemistry which
      underwent considerable modification. The activated carbons made with a mixture of
      reinforcing fibre and coal experienced the largest degree of oxidation, and so
      had more acid surface groups. The adsorption of reactive dye was governed by the
      mesoporous volume, whilst surface chemistry played only a secondary role.
      However, the surface chemistry of the activated carbons and dispersive
      interactions played a key role in the adsorption of the basic dye. The adsorption
      of the reactive dye was more favored in a solution of pH 2, whereas the basic dye
      was adsorbed more easily in a solution of pH 12. 

PMID- 26295196
TI  - Introduction of thiol moieties, including their thiol-ene reactions and air
      oxidation, onto polyelectrolyte multilayer substrates.
AB  - We describe the derivatization of uncross-linked and cross-linked layer-by-layer
      (LbL) assemblies of polyelectrolytes (polyallylamine hydrochloride and
      polyacrylic acid) with sulfydryl groups via Traut's reagent (2-iminothiolane).
      This thiolation was optimized with regards to temperature, concentration, and pH.
      The stability of the resulting -SH groups in the air was determined by X-ray
      photoelectron spectroscopy (XPS). This air oxidation has obvious implications for
      the use of thiol-ene reactions in materials chemistry, and there appears to be
      little on this topic in the literature. Three main S 2s signals were observed by
      XPS: at 231.5 eV (oxidized sulfur), 227.6 eV (thiol groups), and 225.4 eV
      (thiolate groups). Due to their rapid oxidation, we recommend that thiolated
      surfaces be used immediately after they are prepared. As driven by 254 nm UV
      light, thiol groups on polyelectrolyte multilayers react with 1,2-polybutadiene
      (PBd), and residual carbon-carbon double bonds on adsorbed PBd similarly react
      with another thiol. In the case of a fluorinated thiol, surfaces with high water
      contact angles (ca. 120 degrees ) are obtained. Modest exposures to light result
      in derivatization, while longer exposures damage the assemblies. Polyelectrolyte
      thiol-PBd-thiol assemblies delaminate from their substrates when immersed for
      long periods of time in water. Surface silanization with an amino silane prevents
      this delamination and leads to stable assemblies. These assemblies withstand
      various stability tests. Techniques used to analyze the materials in this study
      include X-ray photoelectron spectroscopy (XPS), spectroscopic ellipsometry (SE),
      atomic force microscopy (AFM), and contact angle goniometry.

PMID- 26295197
TI  - Use and Perceived Impact of the County Health Rankings Report in Florida and
      North Carolina.
AB  - OBJECTIVE: Examine overall level of and variation in local health department
      (LHD) use and perceived impact of the County Health Rankings report (Rankings) in
      Florida (2010, 2011) and North Carolina (2010-2012, 2013). DESIGN: Two cross
      sectional surveys among LHDs. PARTICIPANTS: Local health directors and relevant
      staff. MAIN OUTCOME MEASURES: Use of the Rankings was measured by asking
      respondents if their LHD had used the Rankings in any of 10 ways and through
      assessment of community engagement. Perceived impact was measured by amount of
      attention the Rankings received from various stakeholders and whether they had
      already produced or would likely produce any of 7 possible results. RESULTS:
      Overall, LHDs used the Rankings most often to educate staff in Florida (78%) and
      North Carolina (56%). Engagement with community groups around the Rankings was
      variable. Media engagement, through press releases (41%; 40%) or interviews (51%;
      36%) in Florida and North Carolina, was moderate. Florida LHDs used the Rankings
      in more ways and significantly more frequently than North Carolina LHDs. There
      were few significant differences in perceived impact by state. At least a
      moderate amount of attention was received from media in Florida (52%) and North
      Carolina (46%). Twenty-percent of LHDs reported the Rankings received at least
      moderate attention from the general public in both states and 38% (Florida) and
      33% (North Carolina) from policy makers. Tangible benefits to communities from
      the Rankings, such as having already influenced adoption of new policies, were
      modest in Florida (3%) and North Carolina (11%). CONCLUSIONS: Results suggest
      that tangible benefits to communities from use of the Rankings have yet to be
      fully realized but are encouraging. More effective media engagement could produce
      the community awareness necessary to maximize the Rankings' potential to mobilize
      communities for health improvement. State variation in Rankings use suggests that
      more support to LHDs may be helpful.

PMID- 26295198
TI  - Novel method for setting up 3D navigation system with skin-fixed dynamic
      reference frame in anterior cervical surgery.
AB  - PURPOSE: To introduce easy and useful methods using 3D navigation system with
      skin-fixed dynamic reference frame (DRF) in anterior cervical surgery and to
      validate its accuracy. METHODS: From September 2012 to May 2013, 31 patients
      underwent anterior cervical surgery and a total of 48 caspar distraction pins
      were inserted into each cervical vertebra. Every operation was performed using O
      arm(r) navigation system with skin-fixed DRF. To validate the accuracy of these
      methods, a custom-made metal sleeve was used. In surgical field, through the
      metal sleeve, the tip of a navigation probe promptly contacts to the tip of
      caspar pin. We measured the vertical and horizontal distances and the angular
      deviation in sagittal plane between the caspar pin and the navigation probe on
      the virtual images and evaluated accuracy of navigation system with skin fixed
      DRF. RESULTS: Total 31 (males 20, females 11) patients and 48 caspar pins were
      included in this study. The mean horizontal distance between the caspar pin and
      the navigation probe displayed in navigation monitor was 0.49 +/- 0.71 mm. The
      mean vertical distance between the caspar pin and the navigation probe displayed
      in navigation monitor was 0.88 +/- 0.93 mm. And the mean angular deviation in
      sagittal plane between the caspar pin and the navigation probe displayed in
      navigation monitor was 0.59 +/- 0.55 degrees . CONCLUSIONS: 3D navigation system
      with skin-fixed DRF in anterior cervical surgery is a simple and reliable method
      and it can be a helpful supplement to a spine surgeon's judgement.

PMID- 26295199
TI  - Changing Attitudes Through Social Influence: Does Social Distance Matter?
AB  - To test the effects of social influence and social distance on attitudes, we
      assessed judgments of gay and lesbian targets in various contexts over three
      studies (n = 814, 51% female). We compared the impact of a derogatory message to
      a relatively favorable message ostensibly written by another participant.
      Participants were robustly moved by the feedback; social influence was a
      significant predictor in final evaluations of the target, as was social distance.
      Discrimination against gay men and lesbian women appears not to be a fixed
      behavior; seemingly anyone can be persuaded to discriminate or not to
      discriminate by mere peer suggestion.

PMID- 26295201
TI  - Synthesis, Radiolabeling, and In Vivo Imaging of PEGylated High-Generation
      Polyester Dendrimers.
AB  - A fifth generation aliphatic polyester dendrimer was functionalized with vinyl
      groups at the periphery and a dipicolylamine Tc(I) chelate at the core. This
      structure was PEGylated with three different molecular weight mPEGs (mPEG160,
      mPEG350, and mPEG750) using thiol-ene click chemistry. The size of the resulting
      macromolecules was evaluated using dynamic light scattering, and it was found
      that the dendrimer functionalized with mPEG750 was molecularly dispersed in
      water, exhibiting a hydrodynamic diameter of 9.2 +/- 2.1 nm. This PEGylated
      dendrimer was subsequently radiolabeled using [(99m)Tc(CO)3(H2O)3](+) and
      purified to high (>99%) radiochemical purity. Imaging studies were initially
      performed on healthy rats to allow comparison to previous Tc-labeled dendrimers
      and then on xenograft murine tumor models, which collectively showed that the
      dendrimers circulated in the blood for an extended period of time (up to 24 h).
      Furthermore, the radiolabeled dendrimer accumulated in H520 xenograft tumors,
      which could be visualized by single-photon emission computed tomography (SPECT).
      The reported PEGylated aliphatic polyester dendrimers represent a new platform
      for developing tumor-targeted molecular imaging probes and therapeutics. 

PMID- 26295200
TI  - Effect of Laminin-A4 inhibition on cluster formation of human osteoarthritic
      chondrocytes.
AB  - Formation of chondrocyte clusters is not only a morphological sign of
      osteoarthritis but it is also observed in cell culture. Active locomotion of
      chondrocytes is controlled by integrins in vitro. Integrins bind to Laminin-A4
      (LAMA4), a protein that is highly expressed in vivo in clusters of hypertrophic
      chondrocytes. We tested if LAMA4 is relevant for cluster formation. Human
      chondrocytes were cultured in a 2D matrigel model and treated with different
      concentrations of a monoclonal inhibitory anti-LAMA4-antibody. Migration and
      cluster formation was analysed using live cell imaging technique. Full genome
      gene expression analysis was performed to assess the effect of LAMA4 inhibition.
      The data set were screened for genes relevant to cell motility. F-actin staining
      was performed to document cytoskeletal changes. Anti-LAMA4 treatment
      significantly reduced the rate of cluster formation in human chondrocytes. Cells
      changed their surface morphology and exhibited fewer protrusions. Expression of
      genes associated with cellular motility and migration was affected by anti-LAMA4
      treatment. LAMA4-integrin signalling affects chondrocyte morphology and gene
      expression in vitro, thereby contributing to cluster formation in human
      osteoarthritic chondrocytes.

PMID- 26295202
TI  - Prophylactic lidocaine for myocardial infarction.
AB  - BACKGROUND: Coronary artery disease is a major public health problem affecting
      both developed and developing countries. Acute coronary syndromes include
      unstable angina and myocardial infarction with or without ST-segment elevation
      (electrocardiogram sector is higher than baseline). Ventricular arrhythmia after
      myocardial infarction is associated with high risk of mortality. The evidence is
      out of date, and considerable uncertainty remains about the effects of
      prophylactic use of lidocaine on all-cause mortality, in particular, in patients
      with suspected myocardial infarction. OBJECTIVES: To determine the clinical
      effectiveness and safety of prophylactic lidocaine in preventing death among
      people with myocardial infarction. SEARCH METHODS: We searched the Cochrane
      Central Register of Controlled Trials (CENTRAL) (2015, Issue 3), MEDLINE Ovid
      (1946 to 13 April 2015), EMBASE (1947 to 13 April 2015) and Latin American
      Caribbean Health Sciences Literature (LILACS) (1986 to 13 April 2015). We also
      searched Web of Science (1970 to 13 April 2013) and handsearched the reference
      lists of included papers. We applied no language restriction in the search.
      SELECTION CRITERIA: We included randomised controlled trials assessing the
      effects of prophylactic lidocaine for myocardial infarction. We considered all
      cause mortality, cardiac mortality and overall survival at 30 days after
      myocardial infarction as primary outcomes. DATA COLLECTION AND ANALYSIS: We
      performed study selection, risk of bias assessment and data extraction in
      duplicate. We estimated risk ratios (RRs) for dichotomous outcomes and measured
      statistical heterogeneity using I(2). We used a random-effects model and
      conducted trial sequential analysis. MAIN RESULTS: We identified 37 randomised
      controlled trials involving 11,948 participants. These trials compared lidocaine
      versus placebo or no intervention, disopyramide, mexiletine, tocainide,
      propafenone, amiodarone, dimethylammonium chloride, aprindine and pirmenol.
      Overall, trials were underpowered and had high risk of bias. Ninety-seven per
      cent of trials (36/37) were conducted without an a priori sample size estimation.
      Ten trials were sponsored by the pharmaceutical industry. Trials were conducted
      in 17 countries, and intravenous intervention was the most frequent route of
      administration.In trials involving participants with proven or non-proven acute
      myocardial infarction, lidocaine versus placebo or no intervention showed no
      significant differences regarding all-cause mortality (213/5879 (3.62%) vs
      199/5848 (3.40%); RR 1.02, 95% CI 0.82 to 1.27; participants = 11727; studies =
      18; I(2) = 15%); low-quality evidence), cardiac mortality (69/4184 (1.65%) vs
      62/4093 (1.51%); RR 1.03, 95% CI 0.70 to 1.50; participants = 8277; studies = 12;
      I(2) = 12%; low-quality evidence) and prophylaxis of ventricular fibrillation
      (76/5128 (1.48%) vs 103/4987 (2.01%); RR 0.78, 95% CI 0.55 to 1.12; participants
      = 10115; studies = 16; I(2) = 18%; low-quality evidence). In terms of sinus
      bradycardia, lidocaine effect is imprecise compared with effects of placebo or no
      intervention (55/1346 (4.08%) vs 49/1203 (4.07%); RR 1.09, 95% CI 0.66 to 1.80;
      participants = 2549; studies = 8; I(2) = 21%; very low-quality evidence). In
      trials involving only participants with proven acute myocardial infarction,
      lidocaine versus placebo or no intervention showed no significant differences in
      all-cause mortality (148/2747 (5.39%) vs 135/2506 (5.39%); RR 1.01, 95% CI 0.79
      to 1.30; participants = 5253; studies = 16; I(2) = 9%; low-quality evidence). No
      significant differences were noted between lidocaine and any other antiarrhythmic
      drug in terms of all-cause mortality and ventricular fibrillation. Data on
      overall survival 30 days after myocardial infarction were not reported. Lidocaine
      compared with placebo or no intervention increased risk of asystole (35/3393
      (1.03%) vs 14/3443 (0.41%); RR 2.32, 95% CI 1.26 to 4.26; participants = 6826;
      studies = 4; I(2) = 0%; very low-quality evidence) and dizziness/drowsiness
      (74/1259 (5.88%) vs 16/1274 (1.26%); RR 3.85, 95% CI 2.29 to 6.47; participants =
      2533; studies = 6; I(2) = 0%; low-quality evidence). Overall, safety data were
      poorly reported and adverse events may have been underestimated. Trial sequential
      analyses suggest that additional trials may not be needed for reliable
      conclusions to be drawn regarding these outcomes. AUTHORS' CONCLUSIONS: This
      Cochrane review found evidence of low quality to suggest that prophylactic
      lidocaine has very little or no effect on mortality or ventricular fibrillation
      in people with acute myocardial infarction. The safety profile is unclear. This
      conclusion is based on randomised controlled trials with high risk of bias.
      However (disregarding the risk of bias), trial sequential analysis suggests that
      additional trials may not be needed to disprove an intervention effect of 20%
      relative risk reduction. Smaller risk reductions might require additional higher
      trials.

PMID- 26295204
TI  - Sildenafil, a phosphodiesterase type 5 inhibitor, attenuates diabetic nephropathy
      in STZ-induced diabetic rats.
AB  - BACKGROUND: The present study evaluates the possible mechanism of sildenafil
      citrate (SIL) for the attenuation of renal failure in diabetic nephropathic (DN)
      animals. METHODS: Diabetic nephropathy was induced by a single dose of
      streptozotocin (STZ) (60 mg/kg, i.p.) and confirmed by assessing the blood and
      urine biochemical parameters on the 28th day of its induction. The selected DN
      animals were treated with glimepiride (0.5 mg/kg, p.o.) and SIL (2.5 mg/kg, p.o.)
      for a period of 6 weeks. Biochemical parameters in blood and urine were estimated
      after the 29th and 70th day of the protocol for the estimation of the effect of
      SIL. RESULT: There were significant alterations in the blood and urine
      biochemical parameters in STZ-treated groups which confirmed DN. There was a
      significant decrease in the triglyceride level in the SIL-only-treated group on
      the 70th day of the protocol. The histopathology study also suggested that SIL
      treatment results in the improvement in the podocyte count in DN animals.
      CONCLUSIONS: The present study concludes that SIL improves the renal function by
      decreasing the triglyceride level and improving the podocyte count in DN animals.

PMID- 26295205
TI  - Exciton Dissociation in CdSe/CdTe Heterostructure Nanorods.
AB  - Type-II heterostructure nanorods hold good prospects for efficient charge
      separation in nano solar cells. Here we employed local density approximation
      (LDA) quality plane wave pseudopotential methods to study exciton dissociation in
      CdSe/CdTe collinear nanorods. We corrected the LDA band gap by approximating GW
      equations, and studied the correlation effect with configuration interaction
      methods. The calculated binding energy and radiative decay time of the charge
      transfer excitons agree well with experiments. The thermally activated escaping
      time is estimated to be shorter than the radiative recombination time, indicating
      the possibility of exciton dissociation if the nonradiative channel is ignored. 

PMID- 26295203
TI  - Generation of GFAP::GFP astrocyte reporter lines from human adult fibroblast
      derived iPS cells using zinc-finger nuclease technology.
AB  - Astrocytes are instrumental to major brain functions, including metabolic
      support, extracellular ion regulation, the shaping of excitatory signaling events
      and maintenance of synaptic glutamate homeostasis. Astrocyte dysfunction
      contributes to numerous developmental, psychiatric and neurodegenerative
      disorders. The generation of adult human fibroblast-derived induced pluripotent
      stem cells (iPSCs) has provided novel opportunities to study mechanisms of
      astrocyte dysfunction in human-derived cells. To overcome the difficulties of
      cell type heterogeneity during the differentiation process from iPSCs to
      astroglial cells (iPS astrocytes), we generated homogenous populations of iPS
      astrocytes using zinc-finger nuclease (ZFN) technology. Enhanced green
      fluorescent protein (eGFP) driven by the astrocyte-specific glial fibrillary
      acidic protein (GFAP) promoter was inserted into the safe harbor adeno-associated
      virus integration site 1 (AAVS1) locus in disease and control-derived iPSCs.
      Astrocyte populations were enriched using Fluorescence Activated Cell Sorting
      (FACS) and after enrichment more than 99% of iPS astrocytes expressed mature
      astrocyte markers including GFAP, S100beta, NFIA and ALDH1L1. In addition, mature
      pure GFP-iPS astrocytes exhibited a well-described functional astrocytic activity
      in vitro characterized by neuron-dependent regulation of glutamate transporters
      to regulate extracellular glutamate concentrations. Engraftment of GFP-iPS
      astrocytes into rat spinal cord grey matter confirmed in vivo cell survival and
      continued astrocytic maturation. In conclusion, the generation of GFAP::GFP-iPS
      astrocytes provides a powerful in vitro and in vivo tool for studying astrocyte
      biology and astrocyte-driven disease pathogenesis and therapy.

PMID- 26295206
TI  - Off-Resonant Optical Excitation of Gold Nanorods: Nanoscale Imprint of
      Polarization Surface Charge Distribution.
AB  - We report on the nanoscale optical characterization of gold nanorods irradiated
      out of their plasmonic resonance. Our approach is based on the reticulation of a
      photopolymerizable formulation locally triggered by enhanced electromagnetic
      fields. The tiny local field enhancement stems from the surface polarization
      charges associated with the electric field discontinuity at the metal/dielectric
      interface. This allows us to get a nanoscale signature of the spatial
      distribution of the surface charge density in metallic nanoparticles irradiated
      off-resonance. 

PMID- 26295207
TI  - Reactive Scattering as a Chemically Specific Analytical Probe of Liquid Surfaces.
AB  - In this Perspective, we highlight some recent progress in the reactive scattering
      of "chemical probe" species such as atoms or small radicals from liquid surfaces.
      We emphasize in particular the evolution of this area from purely dynamical
      studies of the scattering mechanism. The mechanistic understanding that has now
      been gained is sufficiently mature to allow the same methods to be used as an
      effective analytical tool. The use of this approach to measure liquid-surface
      composition and structure is illustrated through the scattering of O((3)P) atoms
      from a common, imidazolium-based family of ionic liquids. 

PMID- 26295208
TI  - Direct Measurement of the Kinetics and Thermodynamics of Association of
      Hydrophobic Molecules from Molecular Dynamics Simulations.
AB  - A detailed study of the kinetics and thermodynamics of associations of model
      hydrophobic molecules is likely to be valuable for understanding the fundamental
      driving forces for processes such as protein folding and protein-protein
      association. To this end, we present results from a series of 500 ns long
      molecular dynamics (MD) simulations examining associations of 13 types of
      different alkane pairs in explicit water. In addition to providing accurate
      measurements of the association thermodynamics, the unbiased nature of the
      configurational sampling in the MD simulations allows the association and
      dissociation kinetics to be directly quantified. We show that by choosing a
      suitable reaction coordinate, the computed free energies of all of the alkane
      alkane complexes can be linearly related to their buried molecular surface areas,
      that their dissociation kinetics can be reliably estimated from the height of the
      barrier on the computed free energy surfaces, and that their association kinetics
      are effectively diffusion-limited. 

PMID- 26295209
TI  - High-Resolution Electron Spectroscopy of Gas-Phase Metal-Aromatic Complexes.
AB  - High-resolution electron spectroscopy combines pulsed field ionization zero
      electron kinetic energy (ZEKE) detection with in situ laser-assisted synthesis
      and supersonic expansion. The technique offers sub-meV spectral resolution for
      the electron spectra of metal complexes and is a powerful tool to study their
      bonding and structures. This Perspective presents recent progress in single
      photon ZEKE spectroscopy of metal-aromatic complexes and focuses on the
      determination of the electron spin multiplicities, metal binding sites and modes,
      rotational conformers, and conformational changes of these critical species in
      organometallic chemistry. 

PMID- 26295210
TI  - Looking Beyond the First Anniversary.

PMID- 26295211
TI  - Isotope Effects on the Nonequilibrium Dynamics of Ultrafast Photoinduced Proton
      Coupled Electron Transfer Reactions in Solution.
AB  - The hydrogen/deuterium isotope effects on the ultrafast dynamics of photoinduced
      proton-coupled electron transfer (PCET) are investigated with a recently
      developed nonadiabatic dynamics approach. An ensemble of surface hopping
      trajectories is propagated according to a Langevin equation on electron-proton
      vibronic free energy surfaces that depend on a collective solvent coordinate. The
      calculations illustrate that ultrafast PCET reactions could exhibit a significant
      normal isotope effect, where PCET is faster for hydrogen than deuterium, but
      could also exhibit a negligible isotope effect or even a slight inverse isotope
      effect. The isotope effect is very small or absent when highly excited electron
      proton vibronic states dictate the nonadiabatic dynamics and increases with
      greater participation of lower vibronic states. Thus, although the presence of a
      significant isotope effect strongly suggests that proton motion is coupled to
      electron transfer, the absence of an isotope effect does not exclude the
      possibility that proton transfer accompanies electron transfer in ultrafast
      photoinduced charge transfer processes. 

PMID- 26295212
TI  - Long-Range Architecture of Single Lipid-Based Complex Nanoparticles with Local
      Hexagonal Packing.
AB  - The three-dimensional architecture of single nanoparticles made of inverse
      micellar lipids templated on polyelectrolytes and exhibiting a local hexagonal
      packing is elucidated by high-resolution cryoelectron microscopy and coarse
      grained Monte Carlo simulations. Cryoelectron microscopy demonstrates that the
      internal structure of the complexes is less ordered than commonly recognized from
      X-ray diffraction. We have devised a coarse-grained model of self-avoiding
      flexible tubes mimicking the lipid-coated polyelectrolytes and interacting via a
      short-range attractive potential. Consistently with cryoelectron microscopy, the
      resulting clusters obtained through a Monte Carlo scheme exhibit a varying degree
      of order ranging from weakly organized aggregates to partially organized spooled
      and straight bundles, depending on the length and on the persistence length of
      the tubes. These findings may help in the design of self-assembled lipid-based
      complexes for biomedical and nanotechnological applications. 

PMID- 26295213
TI  - Corrections to Publications in J. Phys. Chem. Lett. Volume 2, Issue 1.

PMID- 26295214
TI  - Nursing-Centric Technology and Usability A Call to Action.

PMID- 26295217
TI  - Computing the Anharmonic Vibrational Spectrum of UF6 in 15 Dimensions with an
      Optimized Basis Set and Rectangular Collocation.
AB  - The anharmonic vibrational spectrum of UF6 is computed in full dimensionality
      directly from ab initio data, i.e., bypassing the construction of a potential
      energy surface (PES). The vibrational Schrodinger equation is solved by fitting
      parameters of an adaptable basis using a modified version of the rectangular
      collocation algorithm of Manzhos and Carrington (J. Chem. Phys . 2013, 139,
      051101). The basis functions are products of parametrized Hermite polynomials
      that impose approximate nodal structure. The Schrodinger equation is solved in
      normal coordinates. The results show that anharmonicity and coupling do
      noticeably affect the vibrational transitions, shifting them by several cm(-1).
      Although UF6 has 15 coordinates, we compute hundreds of levels with fewer than
      1000 basis functions and about 50,000 ab initio points. It is the efficiency of
      the basis that makes it possible to forego a PES.

PMID- 26295218
TI  - Modeling sensitive parrotfish (Labridae: Scarini) habitats along the Brazilian
      coast.
AB  - In coral reef environments, there is an increasing concern over parrotfish
      (Labridae: Scarini) due to their rising exploitation by commercial small-scale
      fisheries, which is leading to significant changes in the reefs' community
      structure. Three species, Scarus trispinosus (Valenciennes, 1840), Sparisoma
      frondosum (Agassiz, 1831) and Sparisoma axillare (Steindachner, 1878), currently
      labeled as threatened, have been intensively targeted in Brazil, mostly on the
      northeastern coast. Despite their economic importance, ecological interest and
      worrisome conservation status, not much is known about which variables determine
      their occurrence. In this study, we adopted a hierarchical Bayesian spatial
      temporal approach to map the distribution of these three species along the
      Brazilian coast, using landing data from three different gears (gillnets, spear
      guns, and handlines) and environmental variables (bathymetry, shore distance,
      seabed slope, Sea Surface Temperature and Net Primary Productivity). Our results
      identify sensitive habitats for parrotfish along the Brazilian coast that would
      be more suitable to the implementation of spatial-temporal closure measures,
      which along with the social component fishers could benefit the management and
      conservation of these species. 

PMID- 26295219
TI  - Preformulation Studies of Bee Venom for the Preparation of Bee Venom-Loaded PLGA
      Particles.
AB  - It is known that allergic people was potentially vulnerable to bee venom (BV),
      which can induce an anaphylactic shock, eventually leading to death. Up until
      recently, this kind of allergy was treated only by venom immunotherapy (VIT) and
      its efficacy has been recognized worldwide. This treatment is practiced by
      subcutaneous injections that gradually increase the doses of the allergen. This
      is inconvenient for patients due to frequent injections. Poly (D,L-lactide-co
      glycolide) (PLGA) has been broadly studied as a carrier for drug delivery systems
      (DDS) of proteins and peptides. PLGA particles usually induce a sustained
      release. In this study, the physicochemical properties of BV were examined prior
      to the preparation of BV-loaded PLGA nanoparticles NPs). The content of melittin,
      the main component of BV, was 53.3%. When protected from the light BV was stable
      at 4  degrees C in distilled water, during 8 weeks. BV-loaded PLGA particles were
      prepared using dichloromethane as the most suitable organic solvent and two min
      of ultrasonic emulsification time. This study has characterized the
      physicochemical properties of BV for the preparation BV-loaded PLGA NPs in order
      to design and optimize a suitable sustained release system in the future. 

PMID- 26295220
TI  - Phytophthora austrocedri Elicitates Changes in Diterpene Profile of Austrocedrus
      chilensis.
AB  - The populations of the Andean Cupressaceae Austrocedrus chilensis have been
      severely affected by a disease caused by the phytopathogenic fungus Phytophthora
      austrocedri. A study was undertaken to disclose changes in the resin composition
      of P. austrocedri-infected individuals, including naturally infected and
      artificially inoculated trees, compared with healthy A. chilensis trees. GC-MS
      and (1)H-NMR studies showed a clear differentiation among healthy and infected
      resins, with the diterpene isopimara-8(9),15-dien-19-ol as a relevant constituent
      in resins from infected trees. The effect of resin fractions from P. austrocedri
      infected trees on the pathogen was assessed by measuring the mycelial growth in
      agar plates. The most active fractions from resin obtained from infected trees
      inhibited fungal growth by nearly 50% at 1 mg/dish (35.37 ug/cm(2)). The main
      constituent in the active fractions were 18-hydroxymanool and the aldehyde
      torulosal. Both compounds are oxidation products of manool and can be a chemical
      response of the tree to the pathogen or be formed from the pathogen as a
      biotransformation product of manool by microbial oxidation. While the diterpene
      profiles from A. chilensis tree resins can easily differentiate healthy and P.
      austrocedri infected individuals, the possible conversion of manool to the
      antifungal derivatives 4 and 6 by the microorganism remains to be established. 

PMID- 26295221
TI  - Addition of CFCl3 to Aromatic Aldehydes via in Situ Grignard Reaction.
AB  - Synthetic modification of trichlorofluoromethane (CFCl3) to non-volatile and
      useful fluorinated precursors is a cost-effective and an environmentally benign
      strategy for the safe consumption/destruction of the ozone depleting potential of
      the reagent. In this report, we present a novel method for in situ Grignard
      reaction using magnesium powder and CFCl3 for synthesis of dichlorofluoromethyl
      aromatic alcohols. 

PMID- 26295222
TI  - Unconventional Bifunctional Lewis-Bronsted Acid Activation Mode in Bicyclic
      Guanidine-Catalyzed Conjugate Addition Reactions.
AB  - DFT calculations have demonstrated that the unconventional bifunctional Bronsted
      Lewis acid activation mode is generally applicable to a range of nucleophilic
      conjugate additions catalyzed by bicyclic guanidine catalysts. It competes
      readily with the conventional bifunctional Bronsted acid mode of activation. The
      optimal pro-nucleophiles for this unconventional bifunctional activation are
      acidic substrates with low pKa, while the best electrophiles are flexible 1,4
      diamide and 1,4-diester conjugated systems. 

PMID- 26295223
TI  - Porphyrins as Corrosion Inhibitors for N80 Steel in 3.5% NaCl Solution:
      Electrochemical, Quantum Chemical, QSAR and Monte Carlo Simulations Studies.
AB  - The inhibition of the corrosion of N80 steel in 3.5 wt. % NaCl solution saturated
      with CO2 by four porphyrins, namely 5,10,15,20-tetrakis(4-hydroxyphenyl)-21H,23H
      porphyrin (HPTB), 5,10,15,20-tetra(4-pyridyl)-21H,23H-porphyrin (T4PP),
      4,4',4",4'''-(porphyrin-5,10,15,20-tetrayl)tetrakis(benzoic acid) (THP) and
      5,10,15,20-tetraphenyl-21H,23H-porphyrin (TPP) was studied using electrochemical
      impedance spectroscopy (EIS), potentiodynamic polarization, scanning
      electrochemical microscopy (SECM) and scanning electron microscopy (SEM)
      techniques. The results showed that the inhibition efficiency, eta% increases
      with increasing concentration of the inhibitors. The EIS results revealed that
      the N80 steel surface with adsorbed porphyrins exhibited non-ideal capacitive
      behaviour with reduced charge transfer activity. Potentiodynamic polarization
      measurements indicated that the studied porphyrins acted as mixed type
      inhibitors. The SECM results confirmed the adsorption of the porphyrins on N80
      steel thereby forming a relatively insulated surface. The SEM also confirmed the
      formation of protective films of the porphyrins on N80 steel surface thereby
      protecting the surface from direct acid attack. Quantum chemical calculations,
      quantitative structure activity relationship (QSAR) were also carried out on the
      studied porphyrins and the results showed that the corrosion inhibition
      performances of the porphyrins could be related to their EHOMO, ELUMO, omega, and
      MU values. Monte Carlo simulation studies showed that THP has the highest
      adsorption energy, while T4PP has the least adsorption energy in agreement with
      the values of sigma from quantum chemical calculations. 

PMID- 26295225
TI  - How Common Is Disorder? Occurrence of Disordered Residues in Four Domains of
      Life.
AB  - Disordered regions play important roles in protein adaptation to challenging
      environmental conditions. Flexible and disordered residues have the highest
      propensities to alter the protein packing. Therefore, identification of
      disordered/flexible regions is important for structural and functional analysis
      of proteins. We used the IsUnstruct program to predict the ordered or disordered
      status of residues in 122 proteomes, including 97 eukaryotic and 25 large
      bacterial proteomes larger than 2,500,000 residues. We found that bacterial and
      eukaryotic proteomes contain comparable fraction of disordered residues, which
      was 0.31 in the bacterial and 0.38 in the eukaryotic proteomes. Additional
      analysis of the total of 1540 bacterial proteomes of various sizes yielded a
      smaller fraction of disordered residues, which was only 0.26. Together, the
      results showed that the larger is the size of the proteome, the larger is the
      fraction of the disordered residues. A continuous dependence of the fraction of
      disordered residues on the size of the proteome is observed for four domains of
      life: Eukaryota, Bacteria, Archaea, and Viruses. Furthermore, our analysis of 122
      proteomes showed that the fraction of disordered residues increased with
      increasing the length of homo-repeats for polar, charged, and small residues, and
      decreased for hydrophobic residues. The maximal fraction of disordered residues
      was obtained for proteins containing lysine and arginine homo-repeats. The
      minimal fraction was found in valine and leucine homo-repeats. For 15-residue
      long homo-repeats these values were 0.2 (for Val and Leu) and 0.7 (for Lys and
      Arg). 

PMID- 26295224
TI  - Plasma-Derived Fibronectin Stimulates Chondrogenic Differentiation of Human
      Subchondral Cortico-Spongious Progenitor Cells in Late-Stage Osteoarthritis.
AB  - Migration and chondrogenesis of human subchondral cortico-spongious progenitor
      cells (SPCs) are the key steps in the repair of microfracture-induced articular
      cartilage defects. The aim of this study was to evaluate the effect of human
      plasma-derived fibronectin (Fn) on the chondrogenic differentiation of SPCs,
      which was isolated from subchondrol cortico-spongious bone of late-stage
      osteoarthritis (OA) patients. SPCs were isolated and cultured for three passages.
      Stem cell surface antigens of SPCs were analyzed by flow cytometry. The
      osteogenic, chondrogenic and adipogenic differentiation potential were detected
      by histological staining. The chondrogenesis potential of SPCs with or without
      stimulation of either Fn or BMP-2 were studied by immunochemical staining and
      gene expression analysis. Cells isolated from subchondral bone presented to be
      positive for CD44, CD73, CD90, and CD166, and showed high capacity of osteogenic,
      adipogenic and chondrogenic differentiation, which suggested this cell population
      to be MSC-like cells. Stimulating with Fn increased the expression of SOX-9,
      aggrecan, collagen II while decreased the formation of collagen I by
      immunochemical staining. Gene expression analysis showed similar results. These
      results suggest that plasma-derived Fn can increase the chondrogenic
      differentiation of SPCs isolated from late-stage OA and improve cartilage repair
      after microfracture. 

PMID- 26295226
TI  - Terpenoids from the Octocoral Sinularia gaweli.
AB  - Two eudesmane sesquiterpenoids, verticillatol (1) and 5alpha-acetoxy-4(14)
      eudesmene-1beta-ol (2) and two cembrane diterpenoids, (-)-leptodiol acetate (3)
      and sinulacembranolide A (4) were isolated from the octocoral Sinularia gaweli
      and compounds 2-4 are new isolates. The structures of new terpenoids 2-4 were
      elucidated by spectroscopic methods and by comparison the spectral data with
      those of known analogues. Terpenoid 4 was found to inhibit the accumulation of
      the pro-inflammatory inducible nitric oxide synthase (iNOS) protein of the
      lipopolysaccharide (LPS)-stimulated RAW264.7 marcophage cells. 

PMID- 26295227
TI  - Intracellular Delivery of Molecular Cargo Using Cell-Penetrating Peptides and the
      Combination Strategies.
AB  - Cell-penetrating peptides (CPPs) can cross cellular membranes in a non-toxic
      fashion, improving the intracellular delivery of various molecular cargos such as
      nanoparticles, small molecules and plasmid DNA. Because CPPs provide a safe,
      efficient, and non-invasive mode of transport for various cargos into cells, they
      have been developed as vectors for the delivery of genetic and biologic products
      in recent years. Most common CPPs are positively charged peptides. While
      delivering negatively charged molecules (e.g., nucleic acids) to target cells,
      the internalization efficiency of CPPs is reduced and inhibited because the
      cationic charges on the CPPs are neutralized through the covering of CPPs by
      cargos on the structure. Even under these circumstances, the CPPs can still be
      non-covalently complexed with the negatively charged molecules. To address this
      issue, combination strategies of CPPs with other typical carriers provide a
      promising and novel delivery system. This review summarizes the latest research
      work in using CPPs combined with molecular cargos including liposomes, polymers,
      cationic peptides, nanoparticles, adeno-associated virus (AAV) and calcium for
      the delivery of genetic products, especially for small interfering RNA (siRNA).
      This combination strategy remedies the reduced internalization efficiency caused
      by neutralization. 

PMID- 26295228
TI  - Therapeutic Strategies and New Intervention Points in Chronic Hepatitis Delta
      Virus Infection.
AB  - Chronic hepatitis delta virus infection (CHD) is a condition arising from super
      infection of hepatitis B virus (HBV)-infected patients, resulting in a more rapid
      advance in liver pathology and hepatocellular carcinoma than is observed for HBV
      mono-infection. Although hepatitis delta virus (HDV) is structurally simple, its
      life cycle involves the complex participation of host enzymes, HBV-derived
      surface antigen (HBsAg), and HDV-auto-ribozyme and hepatitis delta antigen (HDAg)
      activities. Unsatisfactory clinical trial results with interferon-based therapies
      are motivating researchers to adjust and redirect the approach to CHD drug
      development. This new effort will likely require additional structural and
      functional studies of the viral and cellular/host components involved in the HDV
      replication cycle. This review highlights recent work aimed at new drug
      interventions for CHD, with interpretation of key pre-clinical- and clinical
      trial outcomes and a discussion of promising new technological approaches to
      antiviral drug design. 

PMID- 26295230
TI  - Design and Implementation of Real-Time Vehicular Camera for Driver Assistance and
      Traffic Congestion Estimation.
AB  - As society has developed, the number of vehicles has increased and road
      conditions have become complicated, increasing the risk of crashes. Therefore, a
      service that provides safe vehicle control and various types of information to
      the driver is urgently needed. In this study, we designed and implemented a real
      time traffic information system and a smart camera device for smart driver
      assistance systems. We selected a commercial device for the smart driver
      assistance systems, and applied a computer vision algorithm to perform image
      recognition. For application to the dynamic region of interest, dynamic frame
      skip methods were implemented to perform parallel processing in order to enable
      real-time operation. In addition, we designed and implemented a model to estimate
      congestion by analyzing traffic information. The performance of the proposed
      method was evaluated using images of a real road environment. We found that the
      processing time improved by 15.4 times when all the proposed methods were applied
      in the application. Further, we found experimentally that there was little or no
      change in the recognition accuracy when the proposed method was applied. Using
      the traffic congestion estimation model, we also found that the average error
      rate of the proposed model was 5.3%. 

PMID- 26295231
TI  - A Micro-Machined Microphone Based on a Combination of Electret and Field-Effect
      Transistor.
AB  - Capacitive-type transduction is now widely used in MEMS microphones. However, its
      sensitivity decreases with reducing size, due to decreasing air gap capacitance.
      In the present study, we proposed and developed the Electret Gate of Field Effect
      Transistor (ElGoFET) transduction based on an electret and FET (field-effect
      transistor) as a novel mechanism of MEMS microphone transduction. The ElGoFET
      transduction has the advantage that the sensitivity is dependent on the ratio of
      capacitance components in the transduction structure. Hence, ElGoFET transduction
      has high sensitivity even with a smaller air gap capacitance, due to a
      miniaturization of the transducer. A FET with a floating-gate electrode embedded
      on a membrane was designed and fabricated and an electret was fabricated by ion
      implantation with Ga(+) ions. During the assembly process between the FET and the
      electret, the operating point of the FET was characterized using the static
      response of the FET induced by the electric field due to the trapped positive
      charge at the electret. Additionally, we evaluated the microphone performance of
      the ElGoFET by measuring the acoustic response in air using a semi-anechoic room.
      The results confirmed that the proposed transduction mechanism has potential for
      microphone applications. 

PMID- 26295232
TI  - Statistical Analysis of the Performance of MDL Enumeration for Multiple-Missed
      Detection in Array Processing.
AB  - An accurate performance analysis on the MDL criterion for source enumeration in
      array processing is presented in this paper. The enumeration results of MDL can
      be predicted precisely by the proposed procedure via the statistical analysis of
      the sample eigenvalues, whose distributive properties are investigated with the
      consideration of their interactions. A novel approach is also developed for the
      performance evaluation when the source number is underestimated by a number
      greater than one, which is denoted as "multiple-missed detection", and the
      probability of a specific underestimated source number can be estimated by ratio
      distribution analysis. Simulation results are included to demonstrate the
      superiority of the presented method over available results and confirm the
      ability of the proposed approach to perform multiple-missed detection analysis. 

PMID- 26295229
TI  - Double Variational Binding--(SMILES) Conformational Analysis by Docking
      Mechanisms for Anti-HIV Pyrimidine Ligands.
AB  - Variational quantitative binding-conformational analysis for a series of anti-HIV
      pyrimidine-based ligands is advanced at the individual molecular level. This was
      achieved by employing ligand-receptor docking algorithms for each molecule in the
      1,3-disubstituted uracil derivative series that was studied. Such computational
      algorithms were employed for analyzing both genuine molecular cases and their
      simplified molecular input line entry system (SMILES) transformations, which were
      created via the controlled breaking of chemical bonds, so as to generate the
      longest SMILES molecular chain (LoSMoC) and Branching SMILES (BraS)
      conformations. The study identified the most active anti-HIV molecules, and
      analyzed their special and relevant bonding fragments (chemical alerts), and the
      recorded energetic and geometric docking results (i.e., binding and affinity
      energies, and the surface area and volume of bonding, respectively). Clear
      computational evidence was also produced concerning the ligand-receptor pocket
      binding efficacies of the LoSMoc and BraS conformation types, thus confirming
      their earlier presence (as suggested by variational quantitative structure
      activity relationship, variational-QSAR) as active intermediates for the molecule
      to-cell transduction process. 

PMID- 26295233
TI  - Mass Load Distribution Dependence of Mass Sensitivity of Magnetoelastic Sensors
      under Different Resonance Modes.
AB  - Magnetoelastic sensors as an important type of acoustic wave sensors have shown
      great promise for a variety of applications. Mass sensitivity is a key parameter
      to characterize its performance. In this work, the effects of mass load
      distribution on the mass sensitivity of a magnetoelastic sensor under different
      resonance modes were theoretically investigated using the modal analysis method.
      The results show that the mass sensitivity and "nodal point" positions are
      related to the point displacement, which is determined by the motion patterns.
      The motion patterns are affected by resonance modes and mass load distribution.
      Asymmetrical mass load distribution causes the motion patterns lose symmetry and
      leads to the shift of "nodal point". The mass sensitivity changing with mass load
      distribution behaves like a sine wave with decaying amplitude and the minimum
      mass sensitivity appears at the first valley. This study provides certain
      theoretical guidance for optimizing the mass sensitivity of a magnetoelastic
      sensor or other acoustic wave based sensors. 

PMID- 26295234
TI  - An Intelligent System Proposal for Improving the Safety and Accessibility of
      Public Transit by Highway.
AB  - The development of public transit systems that are accessible and safe for
      everyone, including people with special needs, is an objective that is justified
      from the civic and economic points of view. Unfortunately, public transit
      services are conceived for people who do not have reduced physical or cognitive
      abilities. In this paper, we present an intelligent public transit system by
      highway with the goal of facilitating access and improving the safety of public
      transit for persons with special needs. The system is deployed using components
      that are commonly available in transport infrastructure, e.g., sensors, mobile
      communications systems, and positioning systems. In addition, the system can
      operate in non-urban transport contexts, e.g., isolated rural areas, where the
      availability of basic infrastructure, such as electricity and communications
      infrastructures, is not always guaranteed. To construct the system, the
      principles and techniques of Ubiquitous Computing and Ambient Intelligence have
      been employed. To illustrate the utility of the system, two cases of services
      rendered by the system are described: the first case involves a surveillance
      system to guarantee accessibility at bus stops; the second case involves a route
      assistant for blind people. 

PMID- 26295236
TI  - An Autonomous Self-Aware and Adaptive Fault Tolerant Routing Technique for
      Wireless Sensor Networks.
AB  - We propose an autonomous self-aware and adaptive fault-tolerant routing technique
      (ASAART) for wireless sensor networks. We address the limitations of self-healing
      routing (SHR) and self-selective routing (SSR) techniques for routing sensor
      data. We also examine the integration of autonomic self-aware and adaptive fault
      detection and resiliency techniques for route formation and route repair to
      provide resilience to errors and failures. We achieved this by using a combined
      continuous and slotted prioritized transmission back-off delay to obtain local
      and global network state information, as well as multiple random functions for
      attaining faster routing convergence and reliable route repair despite transient
      and permanent node failure rates and efficient adaptation to instantaneous
      network topology changes. The results of simulations based on a comparison of the
      ASAART with the SHR and SSR protocols for five different simulated scenarios in
      the presence of transient and permanent node failure rates exhibit a greater
      resiliency to errors and failure and better routing performance in terms of the
      number of successfully delivered network packets, end-to-end delay, delivered MAC
      layer packets, packet error rate, as well as efficient energy conservation in a
      highly congested, faulty, and scalable sensor network. 

PMID- 26295235
TI  - Advanced Liquid-Free, Piezoresistive, SOI-Based Pressure Sensors for Measurements
      in Harsh Environments.
AB  - In this paper we present and discuss two innovative liquid-free SOI sensors for
      pressure measurements in harsh environments. The sensors are capable of measuring
      pressures at high temperatures. In both concepts media separation is realized
      using a steel membrane. The two concepts represent two different strategies for
      packaging of devices for use in harsh environments and at high temperatures. The
      first one is a "one-sensor-one-packaging_technology" concept. The second one uses
      a standard flip-chip bonding technique. The first sensor is a "floating-concept",
      capable of measuring pressures at temperatures up to 400  degrees C (constant
      load) with an accuracy of 0.25% Full Scale Output (FSO). A push rod (mounted onto
      the steel membrane) transfers the applied pressure directly to the center-boss
      membrane of the SOI-chip, which is placed on a ceramic carrier. The chip membrane
      is realized by Deep Reactive Ion Etching (DRIE or Bosch Process). A novel
      propertied chip housing employing a sliding sensor chip that is fixed during
      packaging by mechanical preloading via the push rod is used, thereby avoiding
      chip movement, and ensuring optimal push rod load transmission. The second sensor
      can be used up to 350  degrees C. The SOI chips consists of a beam with an
      integrated centre-boss with was realized using KOH structuring and DRIE. The SOI
      chip is not "floating" but bonded by using flip-chip technology. The fabricated
      SOI sensor chip has a bridge resistance of 3250 Omega. The realized sensor chip
      has a sensitivity of 18 mV/um measured using a bridge current of 1 mA. 

PMID- 26295237
TI  - Infrastructure-Less Indoor Localization Using the Microphone, Magnetometer and
      Light Sensor of a Smartphone.
AB  - In this paper, we present the development of an infrastructure-less indoor
      location system (ILS), which relies on the use of a microphone, a magnetometer
      and a light sensor of a smartphone, all three of which are essentially passive
      sensors, relying on signals available practically in any building in the world,
      no matter how developed the region is. In our work, we merge the information from
      those sensors to estimate the user's location in an indoor environment. A
      multivariate model is applied to find the user's location, and we evaluate the
      quality of the resulting model in terms of sensitivity and specificity. Our
      experiments were carried out in an office environment during summer and winter,
      to take into account changes in light patterns, as well as changes in the Earth's
      magnetic field irregularities. The experimental results clearly show the benefits
      of using the information fusion of multiple sensors when contrasted with the use
      of a single source of information. 

PMID- 26295238
TI  - Fuzzy Logic-Based Guaranteed Lifetime Protocol for Real-Time Wireless Sensor
      Networks.
AB  - Few techniques for guaranteeing a network lifetime have been proposed despite its
      great impact on network management. Moreover, since the existing schemes are
      mostly dependent on the combination of disparate parameters, they do not provide
      additional services, such as real-time communications and balanced energy
      consumption among sensor nodes; thus, the adaptability problems remain unresolved
      among nodes in wireless sensor networks (WSNs). To solve these problems, we
      propose a novel fuzzy logic model to provide real-time communication in a
      guaranteed WSN lifetime. The proposed fuzzy logic controller accepts the input
      descriptors energy, time and velocity to determine each node's role for the next
      duration and the next hop relay node for real-time packets. Through the
      simulation results, we verified that both the guaranteed network's lifetime and
      real-time delivery are efficiently ensured by the new fuzzy logic model. In more
      detail, the above-mentioned two performance metrics are improved up to 8%, as
      compared to our previous work, and 14% compared to existing schemes,
      respectively. 

PMID- 26295239
TI  - Identification of Foot Pathologies Based on Plantar Pressure Asymmetry.
AB  - Foot pathologies can negatively influence foot function, consequently impairing
      gait during daily activity, and severely impacting an individual's quality of
      life. These pathologies are often painful and correspond with high or abnormal
      plantar pressure, which can result in asymmetry in the pressure distribution
      between the two feet. There is currently no general consensus on the presence of
      asymmetry in able-bodied gait, and plantar pressure analysis during gait is in
      dire need of a standardized method to quantify asymmetry. This paper investigates
      the use of plantar pressure asymmetry for pathological gait diagnosis. The
      results of this study involving plantar pressure analysis in fifty one
      participants (31 healthy and 20 with foot pathologies) support the presence of
      plantar pressure asymmetry in normal gait. A higher level of asymmetry was
      detected at the majority of the regions in the feet of the pathological
      population, including statistically significant differences in the plantar
      pressure asymmetry in two regions of the foot, metatarsophalangeal joint 3 (MPJ3)
      and the lateral heel. Quantification of plantar pressure asymmetry may prove to
      be useful for the identification and diagnosis of various foot pathologies. 

PMID- 26295240
TI  - Study on the Antifibrotic Effects of Recombinant Shark Hepatical Stimulator
      Analogue (r-sHSA) in Vitro and in Vivo.
AB  - Hepatic fibrosis is an effusive wound healing process, characterized by an
      excessive deposition of extracellular matrix (ECM), as the consequence of chronic
      liver injury of any etiology. Current therapeutic repertoire for hepatic fibrosis
      is limited to withdrawal of the noxious agent, which is not always feasible.
      Hence, in this article, the antifibrotic effects and possible mechanisms of r
      sHSA, a recombinant protein with hepatoprotection potential, were investigated.
      Using NIH/3T3 (mouse embro-fibroblast cell line), skin fibroblasts (human skin
      fibroblasts, SFBs) and HSC-T6 (rat hepatic stellate cell line), the in vitro
      effect of r-sHSA was evaluated by measuring the expression levels of alpha-1 Type
      I collagen (Col1A1) and alpha-smooth muscle actin (alpha-SMA). It turned out
      those fibrosis indicators were typically inhibited by r-sHSA, suggesting its
      capacity in HSCs inactivation. The antifibrotic activity of r-sHSA was further
      investigated in vivo on CCl4-induced hepatic fibrosis, in view of significant
      improvement of the biochemical and histological indicators. More specifically,
      CCl4-intoxication induced a significant increase in serological biomarkers, e.g.,
      transaminase (AST, ALT), and alkaline phosphatase (ALP), as well as disturbed
      hepatic antioxidative status; most of the parameters were spontaneously
      ameliorated to a large extent by withdrawal of CCl4, although the fibrotic lesion
      was observed histologically. In contrast, r-sHSA treatment markedly eliminated
      fibrous deposits and restored architecture of the liver in a dose dependent
      manner, concomitantly with the phenomena of inflammation relief and HSCs
      deactivation. To sum up, these findings suggest a therapeutic potential for r
      sHSA in hepatic fibrosis, though further studies are required. 

PMID- 26295241
TI  - Rare Chromones from a Fungal Mutant of the Marine-Derived Penicillium
      purpurogenum G59.
AB  - Three new and rare chromones, named epiremisporine B (2), epiremisporine B1 (3)
      and isoconiochaetone C (4), along with three known remisporine B (1),
      coniochaetone A (5) and methyl 8-hydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylate
      (6) were isolated from a mutant from the diethyl sulfate (DES) mutagenesis of a
      marine-derived Penicillium purpurogenum G59. The structures of 2-4 including the
      absolute configurations were determined by spectroscopic methods, especially by
      NMR analysis and electronic circular dichroism (ECD) experiments in conjunction
      with calculations. The absolute configuration of the known remisporine B (1) was
      determined for the first time. Compounds 2 and 3 have a rare feature that has
      only been reported in one example so far. The compounds 1-6 were evaluated for
      their cytotoxicity against several human cancer cell lines. The present work
      explored the great potential of our previous DES mutagenesis strategy for
      activating silent fungal pathways, which has accelerated the discovery of new
      bioactive compounds. 

PMID- 26295242
TI  - Are the Traditional Medical Uses of Muricidae Molluscs Substantiated by Their
      Pharmacological Properties and Bioactive Compounds?
AB  - Marine molluscs from the family Muricidae hold great potential for development as
      a source of therapeutically useful compounds. Traditionally known for the
      production of the ancient dye Tyrian purple, these molluscs also form the basis
      of some rare traditional medicines that have been used for thousands of years.
      Whilst these traditional and alternative medicines have not been chemically
      analysed or tested for efficacy in controlled clinical trials, a significant
      amount of independent research has documented the biological activity of extracts
      and compounds from these snails. In particular, Muricidae produce a suite of
      brominated indoles with anti-inflammatory, anti-cancer and steroidogenic
      activity, as well as choline esters with muscle-relaxing and pain relieving
      properties. These compounds could explain some of the traditional uses in wound
      healing, stomach pain and menstrual problems. However, the principle source of
      bioactive compounds is from the hypobranchial gland, whilst the shell and
      operculum are the main source used in most traditional remedies. Thus further
      research is required to understand this discrepancy and to optimise a quality
      controlled natural medicine from Muricidae. 

PMID- 26295243
TI  - The Effects of Lead Exposure on Serum Uric Acid and Hyperuricemia in Chinese
      Adults: A Cross-Sectional Study.
AB  - The aim of this study was to assess the correlation between blood lead levels and
      both serum uric acid and hyperuricemia in adult residents living within an area
      of China with lead pollution. We conducted a cross-sectional analysis of 2120
      subjects (1180 of whom were male) between the ages of 20 and 75 years who had
      undergone health examinations at the Centers for Disease Control and Prevention
      (CDC) in a lead-polluted area of China between January 2013 and August 2014.
      Blood lead was positively correlated with serum uric acid in both males (r =
      0.095, p = 0.001) and females (r = 0.134, p < 0.001). Multivariate linear
      regression analysis demonstrated that for males, blood lead (p = 0.006), age (p =
      0.001), current smoking (p = 0.012), education (p = 0.001), triglycerides (TG) (p
      < 0.001), and serum creatinine (p < 0.001) were independently associated with
      serum uric acid. For females, blood lead (p < 0.001), body mass index (BMI) (p =
      0.009), and TG (p < 0.001) were independently associated with serum uric acid.
      After multiple adjustments, blood lead was significantly associated with a higher
      prevalence of hyperuricemia when female subjects were categorized into quartiles
      (for the highest quartile vs. the lowest quartile, odds ratio (OR) = 2.190; 95%
      confidence interval (CI): 1.106-4.338; p = 0.025); however, no such association
      was observed for male subjects. Continuous lead exposure has an independent
      impact on serum uric acid for both males and females, although this impact is
      more pronounced for females than for males. Lead exposure is significantly
      associated with hyperuricemia for females but not for males.

PMID- 26295244
TI  - Perspectives on Tobacco Product Waste: A Survey of Framework Convention Alliance
      Members' Knowledge, Attitudes, and Beliefs.
AB  - Cigarette butts (tobacco product waste (TPW)) are the single most collected item
      in environmental trash cleanups worldwide. This brief descriptive study used an
      online survey tool (Survey Monkey) to assess knowledge, attitudes, and beliefs
      among individuals representing the Framework Convention Alliance (FCA) about this
      issue. The FCA has about 350 members, including mainly non-governmental tobacco
      control advocacy groups that support implementation of the World Health
      Organization's (WHO) Framework Convention on Tobacco Control (FCTC). Although the
      response rate (28%) was low, respondents represented countries from all six WHO
      regions. The majority (62%) have heard the term TPW, and nearly all (99%)
      considered TPW as an environmental harm. Most (77%) indicated that the tobacco
      industry should be responsible for TPW mitigation, and 72% felt that smokers
      should also be held responsible. This baseline information may inform future
      international discussions by the FCTC Conference of the Parties (COP) regarding
      environmental policies that may be addressed within FCTC obligations. Additional
      research is planned regarding the entire lifecycle of tobacco's impact on the
      environment. 

PMID- 26295245
TI  - Prevalence of Antimicrobial Resistant and Virulent Salmonella spp. in Treated
      Effluent and Receiving Aquatic Milieu of Wastewater Treatment Plants in Durban,
      South Africa.
AB  - In this study, we evaluated the impact of treated wastewater effluent from two
      wastewater treatment plants on the physicochemical parameters and Salmonella spp.
      load of receiving rivers. Presumptive Salmonella spp. were obtained at all
      sampled points including the discharge points, with counts ranging from 0 to 4.14
      log cfu/mL at both plants. Turbidity, chemical and biological oxygen demand were
      found to be high and mostly above the required limit for treated wastewater
      discharge. However, recorded nitrate and phosphate values were very low. Of the
      200 confirmed Salmonella spp. isolates recovered from the treated effluent and
      receiving surface waters, 93% harbored the spiC gene, 84% harbored the misL gene,
      and 87.5% harbored the orfL gene while 87% harbored the pipD gene. The antibiotic
      resistance profile revealed that the isolates were resistant to sulfamethoxazole,
      nalidixic acid and streptomycin, but susceptible to quinolones and third
      generation beta-lactams. These results indicate that in South Africa treated
      effluents are still a major source of contamination of rivers with pathogens such
      as Salmonella. Appropriate steps by the regulatory authorities and workers at the
      treatment plants are needed to enforce stipulated guidelines in order to prevent
      pollution of surface water resources due to the discharge of poorly treated
      effluents. 

PMID- 26295246
TI  - Relationship between Health Literacy, Health-Related Behaviors and Health Status:
      A Survey of Elderly Chinese.
AB  - BACKGROUND: Despite the large volume of research dedicated to health-related
      behavior change, chronic disease costs continue to rise, thus creating a major
      public health burden. Health literacy, the ability to seek, understand, and
      utilize health information, has been identified as an important factor in the
      course of chronic conditions. Little research has been conducted on the
      relationship between health literacy and health-related behaviors and health
      status in elderly Chinese. The aim of this study was to elucidate the
      relationship between health literacy and health-related behaviors and health
      status in China. METHODS: The subjects enrolled in this study were selected based
      on a stratified cluster random sampling design. Information involving >4500 older
      adults in 44 pension institutions in Urumqi, Changji, Karamay, and Shihezi of
      Xinjiang between September 2011 and June 2012 was collected. The Chinese Citizen
      Health Literacy Questionnaire (China Health Education Centre, 2008) and a Scale
      of the General Status were administered and the information was obtained through
      face-to-face inquiries by investigators. A total of 1452 respondents met the
      inclusion criteria. A total of 1452 questionnaires were issued and the valid
      response rate was 96.14% (1396 of 1452). Factors affecting health literacy and
      the relationship to health literacy were identified by one-way ANOVA and a
      multiple linear regression model. RESULTS: The average health literacy level of
      the elderly in nursing homes was relatively low (71.74 +/- 28.35 points). There
      were significant differences in the health literacy score among the factors of
      age, gender, race, education level, household income, marital conditions, and
      former occupation (p < 0.001). The health literacy score was significantly
      associated with smoking, drinking, physical exercise, and health examination (p <
      0.001). The elderly with higher health literacy scores were significantly less
      likely to have risky behaviors (smoking, regular drinking, and lack of physical
      exercise), and in turn significantly more likely to undergo health examinations
      regularly, report good self-rated health, and significantly more likely to access
      sufficient health information from multiple sources (p < 0.001). No differences
      were noted between the health literacy score and BMI (p > 0.05). Multiple linear
      regression analysis showed that the independent influencing factors of health
      literacy included education level, race, former occupation, household income,
      age, physical exercise, health examination, smoking, and health information
      access (p < 0.001). CONCLUSIONS: Health literacy was significantly associated
      with health-related behaviors in elderly Chinese. Further longitudinal studies
      are needed to help confirm that improving health literacy in the elderly may be
      effective in changing health-related behaviors. To reduce risky habits,
      educational interventions to improve health literacy should be simultaneously
      conducted in health promotion work.

PMID- 26295247
TI  - Climate Change and Infectious Disease Risk in Western Europe: A Survey of Dutch
      Expert Opinion on Adaptation Responses and Actors.
AB  - There is growing evidence of climate change affecting infectious disease risk in
      Western Europe. The call for effective adaptation to this challenge becomes
      increasingly stronger. This paper presents the results of a survey exploring
      Dutch expert perspectives on adaptation responses to climate change impacts on
      infectious disease risk in Western Europe. Additionally, the survey explores the
      expert sample's prioritization of mitigation and adaptation, and expert views on
      the willingness and capacity of relevant actors to respond to climate change. An
      integrated view on the causation of infectious disease risk is employed,
      including multiple (climatic and non-climatic) factors. The results show that the
      experts consider some adaptation responses as relatively more cost-effective,
      like fostering interagency and community partnerships, or beneficial to health,
      such as outbreak investigation and response. Expert opinions converge and diverge
      for different adaptation responses. Regarding the prioritization of mitigation
      and adaptation responses expert perspectives converge towards a 50/50 budgetary
      allocation. The experts consider the national government/health authority as the
      most capable actor to respond to climate change-induced infectious disease risk.
      Divergence and consensus among expert opinions can influence adaptation policy
      processes. Further research is necessary to uncover prevailing expert
      perspectives and their roots, and compare these. 

PMID- 26295248
TI  - Assessing the Role of Voluntary Self-Isolation in the Control of Pandemic
      Influenza Using a Household Epidemic Model.
AB  - In the absence of effective vaccines, antiviral drugs and personal protective
      measures, such as voluntary self-isolation, have been a part of preparedness
      plans for the next influenza pandemic. We used a household model to assess the
      effect of voluntary self-isolation on outbreak control when antiviral drugs are
      not provided sufficiently early. We found that the early initiation of voluntary
      self-isolation can overcome the negative effects caused by a delay in antiviral
      drug distribution when enough symptomatic individuals comply with home
      confinement at symptom onset. For example, for the baseline household
      reproduction number RH0 = 2:5, if delays of one or two days occur between
      clinical symptom development and the start of antiviral prophylaxis, then
      compliance rates of q >= 0:41 and q >= 0:6, respectively, are required to achieve
      the same level of effectiveness as starting antiviral prophylaxis at symptom
      onset. When the time to beginning voluntary self-isolation after symptom onset
      increases from zero to two days, this strategy has a limited effect on reducing
      the transmission of influenza; therefore, this strategy should be implemented as
      soon as possible. In addition, the effect of voluntary self-isolation decreases
      substantially with the proportion of asymptomatic infections increasing. 

PMID- 26295249
TI  - Green Infrastructure, Ecosystem Services, and Human Health.
AB  - Contemporary ecological models of health prominently feature the natural
      environment as fundamental to the ecosystem services that support human life,
      health, and well-being. The natural environment encompasses and permeates all
      other spheres of influence on health. Reviews of the natural environment and
      health literature have tended, at times intentionally, to focus on a limited
      subset of ecosystem services as well as health benefits stemming from the
      presence, and access and exposure to, green infrastructure. The sweeping
      influence of green infrastructure on the myriad ecosystem services essential to
      health has therefore often been underrepresented. This survey of the literature
      aims to provide a more comprehensive picture-in the form of a primer-of the many
      simultaneously acting health co-benefits of green infrastructure. It is hoped
      that a more accurately exhaustive list of benefits will not only instigate
      further research into the health co-benefits of green infrastructure but also
      promote consilience in the many fields, including public health, that must be
      involved in the landscape conservation necessary to protect and improve health
      and well-being. 

PMID- 26295250
TI  - Tobacco Use and Exposure to Second-Hand Smoke among Urban Residents: A Community
      Based Investigation.
AB  - OBJECTIVES: In 2005, China acceded to the World Health Organization Framework
      Convention on Tobacco Control (WHO FCTC), the foundation for the global fight
      against tobacco. Certain cities in China have established local regulations to
      control tobacco use ahead of national policy; however, without the enforcement of
      statutory law, some of these regulations are merely lip service. The aim of the
      study was to assess the effects of city policy on smoking prevalence and on
      second-hand smoke (SHS) exposure status among non-smokers in Changchun City.
      METHODS: A cross-sectional survey covering a multiple-stage, representative
      sample of the urban population aged >=15 years was conducted between 1 Dec 2013
      and 31 Jan 2014. The WHO and the US Centers for Disease Control and Prevention
      developed the questionnaires used, which included demographic characteristics,
      smoking behaviors and SHS exposure status. RESULTS: Overall cigarette smoking
      prevalence was 23.5%; daily cigarette smoking prevalence was 21.2%. Smoking
      prevalence and cigarettes consumed per day was higher among men (p < 0.05) and
      those aged 45-64 years (p < 0.05). Among current smokers, 8.1% planned to quit
      within 12 months; 53.4% had no intention of quitting. Overall SHS exposure
      prevalence was 41.9% (workplace) and 34.1% (at home) over the previous 30 days.
      The weighted workplace SHS exposure prevalence increased with age. CONCLUSIONS:
      The high proportion of smokers with no intention of quitting and the high level
      of SHS exposure may constitute one of the most significant barriers to successful
      smoking cessation in the city. A continued drive to promote full implementation
      of the WHO FCTC is still needed.

PMID- 26295251
TI  - Risk Factors for Salmonella, Shiga Toxin-Producing Escherichia coli and
      Campylobacter Occurrence in Primary Production of Leafy Greens and Strawberries.
AB  - The microbiological sanitary quality and safety of leafy greens and strawberries
      were assessed in the primary production in Belgium, Brazil, Egypt, Norway and
      Spain by enumeration of Escherichia coli and detection of Salmonella, Shiga toxin
      producing E. coli (STEC) and Campylobacter. Water samples were more prone to
      containing pathogens (54 positives out of 950 analyses) than soil (16/1186) and
      produce on the field (18/977 for leafy greens and 5/402 for strawberries). The
      prevalence of pathogens also varied markedly according to the sampling region.
      Flooding of fields increased the risk considerably, with odds ratio (OR) 10.9 for
      Salmonella and 7.0 for STEC. A significant association between elevated numbers
      of generic E. coli and detection of pathogens (OR of 2.3 for STEC and 2.7 for
      Salmonella) was established. Generic E. coli was found to be a suitable index
      organism for Salmonella and STEC, but to a lesser extent for Campylobacter.
      Guidelines on frequency of sampling and threshold values for E. coli in
      irrigation water may differ from region to region. 

PMID- 26295252
TI  - Monitoring and Prognosis System Based on the ICF for People with Traumatic Brain
      Injury.
AB  - The objective of this research is to provide a standardized platform to monitor
      and predict indicators of people with traumatic brain injury using the
      International Classification of Functioning, Disability and Health, and analyze
      its potential benefits for people with disabilities, health centers and
      administrations. We developed a platform that allows automatic standardization
      and automatic graphical representations of indicators of the status of
      individuals and populations. We used data from 730 people with acquired brain
      injury performing periodic comprehensive evaluations in the years 2006-2013.
      Health professionals noted that the use of color-coded graphical representation
      is useful for quickly diagnose failures, limitations or restrictions in
      rehabilitation. The prognosis system achieves 41% of accuracy and sensitivity in
      the prediction of emotional functions, and 48% of accuracy and sensitivity in the
      prediction of executive functions. This monitoring and prognosis system has the
      potential to: (1) save costs and time, (2) provide more information to make
      decisions, (3) promote interoperability, (4) facilitate joint decision-making,
      and (5) improve policies of socioeconomic evaluation of the burden of disease.
      Professionals found the monitoring system useful because it generates a more
      comprehensive understanding of health oriented to the profile of the patients,
      instead of their diseases and injuries. 

PMID- 26295253
TI  - Structure and Biophysical Properties of a Triple-Stranded Beta-Helix Comprising
      the Central Spike of Bacteriophage T4.
AB  - Gene product 5 (gp5) of bacteriophage T4 is a spike-shaped protein that functions
      to disrupt the membrane of the target cell during phage infection. Its C-terminal
      domain is a long and slender beta-helix that is formed by three polypeptide
      chains wrapped around a common symmetry axis akin to three interdigitated
      corkscrews. The folding and biophysical properties of such triple-stranded beta
      helices, which are topologically related to amyloid fibers, represent an unsolved
      biophysical problem. Here, we report structural and biophysical characterization
      of T4 gp5 beta-helix and its truncated mutants of different lengths. A soluble
      fragment that forms a dimer of trimers and that could comprise a minimal self
      folding unit has been identified. Surprisingly, the hydrophobic core of the beta
      helix is small. It is located near the C-terminal end of the beta-helix and
      contains a centrally positioned and hydrated magnesium ion. A large part of the
      beta-helix interior comprises a large elongated cavity that binds palmitic,
      stearic, and oleic acids in an extended conformation suggesting that these
      molecules might participate in the folding of the complete beta-helix. 

PMID- 26295254
TI  - Micronutrient Intake in Healthy Toddlers: A Multinational Perspective.
AB  - Adequate nutrient intake during early childhood is of particular importance for
      optimal growth and future health. However, cross-national comparative research on
      nutrient intake of toddlers is still limited. We conducted a literature review to
      examine the nutrient intake in healthy toddlers from some of the world's most
      populous nations currently on different stages of socioeconomic development:
      Brazil, Germany, Russia and the United States. We aimed to identify national
      surveys reporting mean intakes of the following nutrients: vitamins A, D, E,
      folate, calcium, iron and zinc. To calculate the prevalence of inadequate
      nutrient intake, we used a modified version of the Estimated Average Requirement
      cut-point method. Overall, five studies with 6756 toddlers were eligible for
      inclusion in this review. In countries where data were available, a prevalence of
      inadequate intake higher than 20% was found for vitamins A, D, E and calcium. In
      Germany, folate intake also appeared to be inadequate. The results of our review
      indicate that inadequate micronutrient intake in toddlers might be a global
      challenge affecting also affluent countries. However, to explore the full scope
      of this important public health issue joint efforts of researchers worldwide are
      needed to combine existing data and fill in data gaps. 

PMID- 26295255
TI  - Omega-3 Polyunsaturated Fatty Acids Trigger Cell Cycle Arrest and Induce
      Apoptosis in Human Neuroblastoma LA-N-1 Cells.
AB  - Omega-3 (n-3) fatty acids are dietary long-chain fatty acids with an array of
      health benefits. Previous research has demonstrated the growth-inhibitory effect
      of n-3 fatty acids on different cancer cell lines in vitro, yet their anti-tumor
      effects and underlying action mechanisms on human neuroblastoma LA-N-1 cells have
      not yet been reported. In this study, we showed that docosahexaenoic acid (DHA)
      and eicosapentaenoic acid (EPA) exhibited time- and concentration-dependent anti
      proliferative effect on the human neuroblastoma LA-N-1 cells, but had minimal
      cytotoxicity on the normal or non-tumorigenic cells, as measured by MTT reduction
      assay. Mechanistic studies indicated that DHA and EPA triggered G0/G1 cell cycle
      arrest in LA-N-1 cells, as detected by flow cytometry, which was accompanied by a
      decrease in the expression of CDK2 and cyclin E proteins. Moreover, DHA and EPA
      could also induce apoptosis in LA-N-1 cells as revealed by an increase in DNA
      fragmentation, phosphatidylserine externalization and mitochondrial membrane
      depolarization. Up-regulation of Bax, activated caspase-3 and caspase-9 proteins,
      and down-regulation of Bcl-XL protein, might account for the occurrence of
      apoptotic events. Collectively, our results suggest that the growth-inhibitory
      effect of DHA and EPA on LA-N-1 cells might be mediated, at least in part, via
      triggering of cell cycle arrest and apoptosis. Therefore, DHA and EPA are
      potential anti-cancer agents which might be used for the adjuvant therapy or
      combination therapy with the conventional anti-cancer drugs for the treatment of
      some forms of human neuroblastoma with minimal toxicity. 

PMID- 26295256
TI  - Development of a Food Group-Based Diet Score and Its Association with Bone
      Mineral Density in the Elderly: The Rotterdam Study.
AB  - No diet score exists that summarizes the features of a diet that is optimal for
      bone mineral density (BMD) in the elderly. Our aims were (a) to develop a BMD
      Diet Score reflecting a diet that may be beneficial for BMD based on the existing
      literature, and (b) to examine the association of the BMD-Diet Score and the
      Healthy Diet Indicator, a score based on guidelines of the World Health
      Organization, with BMD in Dutch elderly participating in a prospective cohort
      study, the Rotterdam Study (n = 5144). Baseline dietary intake, assessed using a
      food frequency questionnaire, was categorized into food groups. Food groups that
      were consistently associated with BMD in the literature were included in the BMD
      Diet Score. BMD was measured repeatedly and was assessed using dual energy X-ray
      absorptiometry. The BMD-Diet Score considered intake of vegetables, fruits, fish,
      whole grains, legumes/beans and dairy products as "high-BMD" components and meat
      and confectionary as "low-BMD" components. After adjustment, the BMD-Diet Score
      was positively associated with BMD (beta (95% confidence interval) = 0.009
      (0.005, 0.012) g/cm(2) per standard deviation). This effect size was
      approximately three times as large as has been observed for the Healthy Diet
      Indicator. The food groups included in our BMD-Diet Score could be considered in
      the development of future dietary guidelines for healthy ageing. 

PMID- 26295257
TI  - High-Dose Menaquinone-7 Supplementation Reduces Cardiovascular Calcification in a
      Murine Model of Extraosseous Calcification.
AB  - Cardiovascular calcification is prevalent in the aging population and in patients
      with chronic kidney disease (CKD) and diabetes mellitus, giving rise to
      substantial morbidity and mortality. Vitamin K-dependent matrix Gla-protein (MGP)
      is an important inhibitor of calcification. The aim of this study was to evaluate
      the impact of high-dose menaquinone-7 (MK-7) supplementation (100 ug/g diet) on
      the development of extraosseous calcification in a murine model. Calcification
      was induced by 5/6 nephrectomy combined with high phosphate diet in rats. Sham
      operated animals served as controls. Animals received high or low MK-7 diets for
      12 weeks. We assessed vital parameters, serum chemistry, creatinine clearance,
      and cardiac function. CKD provoked increased aortic (1.3 fold; p < 0.05) and
      myocardial (2.4 fold; p < 0.05) calcification in line with increased alkaline
      phosphatase levels (2.2 fold; p < 0.01). MK-7 supplementation inhibited
      cardiovascular calcification and decreased aortic alkaline phosphatase tissue
      concentrations. Furthermore, MK-7 supplementation increased aortic MGP messenger
      ribonucleic acid (mRNA) expression (10-fold; p < 0.05). CKD-induced arterial
      hypertension with secondary myocardial hypertrophy and increased elastic fiber
      breaking points in the arterial tunica media did not change with MK-7
      supplementation. Our results show that high-dose MK-7 supplementation inhibits
      the development of cardiovascular calcification. The protective effect of MK-7
      may be related to the inhibition of secondary mineralization of damaged vascular
      structures. 

PMID- 26295259
TI  - Zearalenone in the Intestinal Tissues of Immature Gilts Exposed per os to
      Mycotoxins.
AB  - Zearalenone and its metabolites, alpha-zearalenol and beta-zearalenol,
      demonstrate estradiol-like activity and disrupt physiological functions in
      animals. This article evaluates the carryover of zearalenone and its selected
      metabolites from the digesta to intestinal walls (along the entire intestines) in
      pre-pubertal gilts exposed to low doses of zearalenone over long periods of time.
      The term "carryover" describes the transfer of mycotoxins from feed to edible
      tissues, and it was used to assess the risk of mycotoxin exposure for consumers.
      The experimental gilts with body weight of up to 25 kg were per os administered
      zearalenone at a daily dose of 40 MUg/kg BW (Group E, n = 18) or placebo (Group
      C, n = 21) over a period of 42 days. In the first weeks of exposure, the highest
      values of the carryover factor were noted in the duodenum and the jejunum. In
      animals receiving pure zearalenone, the presence of metabolites was not
      determined in intestinal tissues. In the last three weeks of the experiment, very
      high values of the carryover factor were observed in the duodenum and the
      descending colon. The results of the study indicate that in animals exposed to
      subclinical doses of zearalenone, the carryover factor could be determined by the
      distribution and expression of estrogen receptor beta. 

PMID- 26295260
TI  - Spatiotemporal Dynamics of Microcystin Variants and Relationships with
      Environmental Parameters in Lake Taihu, China.
AB  - Excessive anthropogenically-caused nutrient loading from both external and
      internal sources has promoted the growth of cyanobacteria in Lake Taihu from 2005
      to 2014, suggesting increased production and release of cyanotoxins. In order to
      explain the spatial distribution and temporal variation of microcystins (MCs),
      the intracellular concentrations of MCs (MC-LR, -RR and -YR, L, R and Y are
      abbreviations of leucine, arginine and tyrosine) were monitored monthly from July
      2013 to June 2014. Three MC variants are present simultaneously in Lake Taihu;
      the MC-LR and -RR variants were dominant (accounting for 40% and 39% of the
      total), followed by MC-YR (21%). However, MC-YR accounted for a higher proportion
      in colder months, especially in March. The highest concentrations of
      intracellular MCs were found in July and October when cyanobacteria cell density
      also reached the maximum. The average concentrations of MC-LR, -RR and -YR in
      July were 4.69, 4.23 and 2.01 MUg/L, respectively. In terms of the entire lake,
      toxin concentrations in northern parts were significantly higher than the eastern
      part in summer, when MC concentrations were several times higher than the
      guideline value by WHO throughout much of Lake Taihu. Results from correlation
      and redundancy analysis (RDA) showed that total MCs, including all variants, were
      strongly and positively correlated with cyanobacteria cell density, water
      temperature, total phosphorus (TP) and pH, whereas each variant had different
      correlation coefficients with each of the considered environmental variables. MC
      RR showed a stronger relationship with temperature, in contrast to MC-YR and -LR.
      Dissolved inorganic carbon (DIC) showed a negative relationship with each
      variant, suggesting that rising DIC concentrations may inhibit cyanobacterial
      growth and thereby reduce MC production in the future. 

PMID- 26295261
TI  - Peri-Operative Management of Older Adults with Cancer-The Roles of the Surgeon
      and Geriatrician.
AB  - Optimal surgical management of older adults with cancer starts pre-operatively.
      The surgeon plays a key role in the appropriate selection of patients and
      procedures, optimisation of their functional status prior to surgery, and
      provision of more intensive care for those who are at high risk of post-operative
      complications. The literature, mainly based on retrospective, non-randomised
      studies, suggests that factors such as age, co-morbidities, pre-operative
      cognitive function and intensity of the surgical procedure all appear to
      contribute to the development of post-operative complications. Several studies
      have shown that a pre-operative geriatric assessment predicts post-operative
      mortality and morbidity as well as survival in older surgical cancer patients.
      Geriatricians are used to working in multidisciplinary teams that assess older
      patients and make individual treatment plans. However, the role of the
      geriatrician in the surgical oncology setting is not well established. A
      geriatrician could be a valuable contribution to the treatment team both in the
      pre-operative stage (patient assessment and pre-operative optimisation) and the
      post-operative stage (patient assessment and treatment of medical complications
      as well as discharge planning). 

PMID- 26295258
TI  - Pharmacological Alternatives for the Treatment of Neurodegenerative Disorders:
      Wasp and Bee Venoms and Their Components as New Neuroactive Tools.
AB  - Neurodegenerative diseases are relentlessly progressive, severely impacting
      affected patients, families and society as a whole. Increased life expectancy has
      made these diseases more common worldwide. Unfortunately, available drugs have
      insufficient therapeutic effects on many subtypes of these intractable diseases,
      and adverse effects hamper continued treatment. Wasp and bee venoms and their
      components are potential means of managing or reducing these effects and provide
      new alternatives for the control of neurodegenerative diseases. These venoms and
      their components are well-known and irrefutable sources of neuroprotectors or
      neuromodulators. In this respect, the present study reviews our current
      understanding of the mechanisms of action and future prospects regarding the use
      of new drugs derived from wasp and bee venom in the treatment of major
      neurodegenerative disorders, including Alzheimer's Disease, Parkinson's Disease,
      Epilepsy, Multiple Sclerosis and Amyotrophic Lateral Sclerosis. 

PMID- 26295262
TI  - In Vitro Activity of Cefepime/AAI101 and Comparators against Cefepime Non
      susceptible Enterobacteriaceae.
AB  - We evaluated the in vitro potency of cefepime combined with AAI101, a novel
      extended-spectrum beta-lactamase inhibitor, against a population of clinical
      Escherichia coli and Klebsiella pneumoniae collected from USA hospitals. Of the
      223 cefepime non-susceptible isolates, 95% were ceftazidime non-susceptible, 49%
      ertapenem non-susceptible, 57% piperacillin/tazobactam non-susceptible, 90% were
      multidrug-resistant (resistant to >=3 drug classes), 22% produced carbapenemases,
      and 67% produced ESBLs. Addition of AAI101 restored the activity of cefepime such
      that the MIC50 was reduced from >64 mg/L for cefepime to 0.13 mg/L for
      cefepime/AAI101, supporting its continued development treatment for infections
      caused by these organisms. 

PMID- 26295263
TI  - Molecular Detection and Characterization of Theileria Infecting Wildebeest
      (Connochaetes taurinus) in the Maasai Mara National Reserve, Kenya.
AB  - Theileria is a genus of tick-borne protozoan that is globally widespread and
      infects nearly all ungulates in which they cause either latent infection or
      lethal disease. Wild animals are considered reservoir hosts of many species of
      Theileria and their diversity in wildlife species is increasingly becoming of
      interest. The molecular characterization and identification of Theileria
      infecting wildlife has been studied in a few species including buffalo, which are
      considered reservoir host for Theileria parva infecting cattle. In this study, we
      sequenced Theileria species infecting wildebeest (Connochaetes taurinus) and used
      molecular-genetic and phylogenetic analysis of the 18 Small Subunit of the
      Ribosomal RNA (18S rRNA) to identify their relationships with known species of
      Theileria. Our results revealed three new Theileria haplotypes infecting
      wildebeest. Phylogenetic analysis revealed that haplotype 1 and 2 clustered in
      the same clade as Theileria separata and with Theileria sp. isolated from other
      small to medium sized antelopes. Haplotype 3 clustered close to the Theileria
      ovis clade. This is the first molecular description and characterization of
      Theileria species infecting blue wildebeest in East Africa. This study
      demonstrates the potential for Theileria transmission between wildebeest and
      small domestic ungulates, such as sheep and goats. 

PMID- 26295264
TI  - MicroRNAs: Emerging Novel Clinical Biomarkers for Hepatocellular Carcinomas.
AB  - The discovery of small non-coding RNAs known as microRNAs has refined our view of
      the complexity of gene expression regulation. In hepatocellular carcinoma (HCC),
      the fifth most frequent cancer and the third leading cause of cancer death
      worldwide, dysregulation of microRNAs has been implicated in all aspects of
      hepatocarcinogenesis. In addition, alterations of microRNA expression have also
      been reported in non-cancerous liver diseases including chronic hepatitis and
      liver cirrhosis. MicroRNAs have been proposed as clinically useful diagnostic
      biomarkers to differentiate HCC from different liver pathologies and healthy
      controls. Unique patterns of microRNA expression have also been implicated as
      biomarkers for prognosis as well as to predict and monitor therapeutic responses
      in HCC. Since dysregulation has been detected in various specimens including
      primary liver cancer tissues, serum, plasma, and urine, microRNAs represent novel
      non-invasive markers for HCC screening and predicting therapeutic responses.
      However, despite a significant number of studies, a consensus on which microRNA
      panels, sample types, and methodologies for microRNA expression analysis have to
      be used has not yet been established. This review focuses on potential values,
      benefits, and limitations of microRNAs as new clinical markers for diagnosis,
      prognosis, prediction, and therapeutic monitoring in HCC. 

PMID- 26295268
TI  - Effectiveness and cost of influenza vaccine reminders for adults with asthma or
      chronic obstructive pulmonary disease.
AB  - OBJECTIVES: To assess the effectiveness and cost of interactive voice response
      (IVR) reminders for influenza vaccination compared with postcards, among adults
      with asthma or chronic obstructive pulmonary disease (COPD). STUDY DESIGN:
      Pragmatic, 3-arm, randomized control trial. METHODS: The trial was conducted in
      an integrated healthcare organization during 2012 and 2013, using an existing IVR
      system. All adults aged 19 through 64 years with asthma or COPD (n = 12,285) were
      randomized to receive 1 of the following vaccination reminders: 1) postcard
      reminder only, 2) IVR reminder only, or 3) postcard plus IVR reminder. The
      primary outcome was influenza vaccination by October 31, 2012; the secondary
      outcomes were influenza vaccination by December 31, 2012, and by March 31, 2013.
      RESULTS: For subjects receiving an IVR call, 57% received a message on their
      answering machine; 27% answered the call; and 16% were not reached. Influenza
      vaccination rates were 29.5%, 31.1%, and 30.6% in the postcard-only, IVR-only,
      and postcard-plus-IVR study arms, respectively. After controlling for relevant
      covariates, IVR reminders were not significantly more or less effective than
      postcard reminders. Program costs were $0.78, $1.23, and $1.93 per subject for
      postcard-only, IVR-only, and postcard-plus-IVR reminders, respectively.
      Extrapolating costs to the entire population at the study site that typically
      receives influenza vaccination reminders (approximately 100,000 individuals),
      reminder costs would have been $0.55, $0.05, and $0.60 per subject for postcard
      only, IVR-only, and postcard-plus-IVR reminders, respectively. CONCLUSIONS: IVR
      reminders are not more effective at promoting influenza vaccination than postcard
      reminders, but IVR reminders may be less expensive for large patient populations.

PMID- 26295265
TI  - Targeting the Checkpoint to Kill Cancer Cells.
AB  - Cancer treatments such as radiotherapy and most of the chemotherapies act by
      damaging DNA of cancer cells. Upon DNA damage, cells stop proliferation at cell
      cycle checkpoints, which provides them time for DNA repair. Inhibiting the
      checkpoint allows entry to mitosis despite the presence of DNA damage and can
      lead to cell death. Importantly, as cancer cells exhibit increased levels of
      endogenous DNA damage due to an excessive replication stress, inhibiting the
      checkpoint kinases alone could act as a directed anti-cancer therapy. Here, we
      review the current status of inhibitors targeted towards the checkpoint effectors
      and discuss mechanisms of their actions in killing of cancer cells. 

PMID- 26295266
TI  - Macrophage Expression of Inflammatory Genes in Response to EMCV Infection.
AB  - The expression and production of type 1 interferon is the classic cellular
      response to virus infection. In addition to this antiviral response, virus
      infection also stimulates the production of proinflammatory mediators. In this
      review, the pathways controlling the induction of inflammatory genes and the
      roles that these inflammatory mediators contribute to host defense against viral
      pathogens will be discussed. Specific focus will be on the role of the chemokine
      receptor CCR5, as a signaling receptor controlling the activation of pathways
      leading to virus-induced inflammatory gene expression. 

PMID- 26295269
TI  - Acupuncture and chiropractic care: utilization and electronic medical record
      capture.
AB  - OBJECTIVES: To describe acupuncture and chiropractic use among patients with
      chronic musculoskeletal pain (CMP) at a health maintenance organization, and
      explore issues of benefit design and electronic medical record (EMR) capture.
      STUDY DESIGN: Cross-sectional survey. METHODS: Kaiser Permanente members meeting
      EMR diagnostic criteria for CMP were invited to participate. The survey included
      questions about self-identified presence of CMP, use of acupuncture and
      chiropractic care, use of ancillary self-care modalities, and communication with
      conventional medicine practitioners. Analysis of survey data was supplemented
      with a retrospective review of EMR utilization data. RESULTS: Of 6068 survey
      respondents, 32% reported acupuncture use, 47% reported chiropractic use, 21%
      used both, and 42% used neither. For 25% of patients using acupuncture and 43% of
      those using chiropractic care, utilization was undetected by the EMR. Thirty-five
      percent of acupuncture users and 42% of chiropractic users did not discuss this
      care with their health maintenance organization (HMO) clinicians. Among
      chiropractic users, those accessing care out of plan were older (P < .01), were
      more likely to use long-term opioids (P = .03), and had more pain diagnoses (P =
      .01) than those accessing care via clinician referral or self-referral. For
      acupuncture, those using the clinician referral mechanism exhibited these same
      characteristics. CONCLUSIONS: A majority of participants had used acupuncture,
      chiropractic care, or both. While benefit structure may materially influence
      utilization patterns, many patients with CMP use acupuncture and chiropractic
      care without regard to their insurance coverage. A substantial percentage of
      acupuncture and chiropractic use thus occurs beyond detection of EMR systems, and
      many patients do not report such care to their HMO clinicians.

PMID- 26295267
TI  - Comparative Geometrical Analysis of Leucine-Rich Repeat Structures in the Nod
      Like and Toll-Like Receptors in Vertebrate Innate Immunity.
AB  - The NOD-like receptors (NLRs) and Toll-like receptors (TLRs) are pattern
      recognition receptors that are involved in the innate, pathogen pattern
      recognition system. The TLR and NLR receptors contain leucine-rich repeats (LRRs)
      that are responsible for ligand interactions. In LRRs short beta-strands stack
      parallel and then the LRRs form a super helical arrangement of repeating
      structural units (called a coil of solenoids). The structures of the LRR domains
      of NLRC4, NLRP1, and NLRX1 in NLRs and of TLR1-5, TLR6, TLR8, TLR9 in TLRs have
      been determined. Here we report nine geometrical parameters that characterize the
      LRR domains; these include four helical parameters from HELFIT analysis. These
      nine parameters characterize well the LRR structures in NLRs and TLRs; the LRRs
      of NLR adopts a right-handed helix. In contrast, the TLR LRRs adopt either a left
      handed helix or are nearly flat; RP105 and CD14 also adopt a left-handed helix.
      This geometrical analysis subdivides TLRs into four groups consisting of
      TLR3/TLR8/TLR9, TLR1/TLR2/TRR6, TLR4, and TLR5; these correspond to the
      phylogenetic tree based on amino acid sequences. In the TLRs an ascending lateral
      surface that consists of loops connecting the beta-strand at the C-terminal side
      is involved in protein, protein/ligand interactions, but not the descending
      lateral surface on the opposite side. 

PMID- 26295270
TI  - Worksite medical home: health services use and claim costs.
AB  - OBJECTIVES: To examine the relationship among use of an on-site employer-provided
      primary care medical home, and health services use and health plan costs for
      inpatient and outpatient services and pharmaceuticals. STUDY DESIGN: The study
      was a retrospective observational analysis of health plan claims, human resources
      data, and Health Care Center (HCC) encounters. METHODS: Three years of data for
      employees and dependents designating the HCC as their primary care provider (HCC
      major users) were compared with data from 2 comparison groups: "casual" HCC users
      and HCC nonusers. The outcomes of interest were: 1) health services utilization,
      and 2) monetized use of the health plan. Secondary data from an employer-provided
      Health Care Center (HCC). RESULTS: After adjusting for several potential
      confounders, HCC major users had less use of external healthcare services than
      the comparison groups (employees had 2.7 fewer external encounters than HCC
      casual users [P < .001] and 1.2 fewer external encounters than nonusers [P <
      .001]; dependents had 3.5 fewer external encounters than HCC casual users [P <
      .001] and 1.9 fewer external encounters than non-users [P < .001]). Annual
      monetized use of the health plan for employees and dependents was highest for HCC
      casual users relative to HCC major users (employees: $482 greater, P < .01;
      dependents: $598 greater, P < .001). CONCLUSIONS: Employees and their dependents
      who were "casual users" of the HCC had the highest claims costs and use of
      outside healthcare services. Additional research is needed to assess the extent
      to which employees' utilization of services at on-site primary care medical homes
      affects employee health outcomes, resulting in potential effects on company
      healthcare plan expenditures, worker productivity, and return on investment.

PMID- 26295271
TI  - The value of colonoscopic colorectal cancer screening of adults aged 50 to 64.
AB  - OBJECTIVES: The purpose of this study was to determine the value of life-years
      saved due to colorectal cancer (CRC) screening with colonoscopy for the
      population aged 50 to 64 years. The cost perspective is that of a private
      (commercial) insurer, while the value perspective includes survival past age 65
      years, when most of the US population is insured by Medicare. We focused on
      colonoscopy because it is not only diagnostic but also therapeutic; because
      positive results on other screening tests generally are followed up with
      colonoscopy; and to build on previous study results that colonoscopy is
      ultimately more cost-effective than other screening, even considering its
      expense. STUDY DESIGN: Monte Carlo simulation. METHODS: Using a large multi-state
      cancer registry, a large national administrative claims database, and a model of
      CRC development based on published clinical literature, we estimated the impact
      of screening with colonoscopy on incidence of CRC, aggregate cost of
      colonoscopies and CRC, and life-years saved. RESULTS: Assuming 2013 commercial
      reimbursement rates for screening and treatment, we found that increasing
      screening adherence from 50% to 100% would cost about $3 per member per month
      (2013 US$) and reduce CRC treatment costs by about $1 per member per month. The
      cost per life-year saved is approximately $12,000, an amount that is much lower
      than for cervical or breast cancer screening and comparable to lung cancer
      screening. CONCLUSIONS: Our results suggest that commercial insurers and
      employers should promote CRC screening as a high-value service. Promoting such
      screening through high-quality, low-cost providers would be an exemplar of
      efficient system innovation.

PMID- 26295272
TI  - Pilot of decision support to individualize colorectal cancer screening
      recommendations.
AB  - OBJECTIVES: To test the feasibility of using an electronic medical record (EMR)
      based decision support system (DSS) that incorporates morbidity and frailty
      information to individualize colorectal cancer (CRC) screening recommendations.
      STUDY DESIGN: Our framework used the payoff time, defined as the minimum time
      until the benefits of screening exceed the harms. METHODS: Subjects were 24
      patients eligible for CRC screening and 22 primary care providers (PCPs).
      Measures included PCP satisfaction with existing reminder systems and with
      decision support. RESULTS: The run-in phase, during which the intervention was
      inactive but its performance was verified, had 14 patients enrolled. The
      intervention phase, during which payoff time and life expectancy calculations
      were used to recommend for or against CRC screening, had 10 patients enrolled. Of
      the 10 patients enrolled in the intervention phase, the DSS recommended in favor
      of CRC screening for 6 patients. (The PCPs also recommended it for those 6
      patients, although 3 refused the screening.) The DSS recommended against CRC
      screening for 4 patients, while the PCPs recommended against it for 3 of those 4
      and ordered the screening for 1 patient. PCPs who had patients enrolled in the
      intervention phase indicated interest in having payoff time information for all
      patients eligible for CRC screening. This pilot study was small and was not
      powered to determine the effect of the intervention on screening behavior.
      CONCLUSIONS: Colorectal cancer screening involves balancing immediate harms with
      longer-term benefits; EMR decision support may facilitate personalized
      benefit/harm assessment. The payoff time framework is feasible for implementation
      in EMR decision support.

PMID- 26295273
TI  - Colorectal cancer screening in the 21st century: where do we go from here?
AB  - Our approach to colorectal cancer screening is undergoing a much-needed paradigm
      shift. The evidence that screening "works" and is of high value is indisputable,
      yet screening remains underused at a population level. In contrast, other data
      suggest overuse of screening. Traditional population-oriented efforts to promote
      screening utilization have not only failed to adequately address underuse, they
      have simultaneously promoted overuse of screening in selected groups of patients.
      Clearly, new approaches are needed if we are to deliver the right care to the
      right patients at the right time. By shifting our focus from populations to
      patients, we can aim to achieve the goal set by Healthy People 2020 of ensuring
      that 70% of the appropriate US population is up-to-date with colorectal cancer
      screening. 

PMID- 26295274
TI  - It's time for CMS to utilize functional assessment as a key quality component.
AB  - This editorial reviews the recently published study (AJMC April) by Gerrard et
      al, titled "Functional Status and Readmissions in Unilateral Hip Fractures,"
      which analyzes the statistical prediction model of the Fitness Index Measure for
      hospital readmission in unilateral hip fractures, and discusses why functional
      assessment should be used in evaluating other conditions. The current method of
      stratifying risk for Core Measure Conditions used by CMS to predict hospital
      readmissions utilizes a largely nonmodifiable formula of age, gender, and medical
      comorbidities. Numerous recent studies have shown that validated functional
      assessment can be a powerful statistical predictor of hospital readmission. The
      author makes the argument for CMS to utilize functional assessment to predict
      hospital readmissions as a part of its Value-Based Purchasing Program. 

PMID- 26295275
TI  - Tuning the Electronic Structure of Fe(II) Polypyridines via Donor Atom and Ligand
      Scaffold Modifications: A Computational Study.
AB  - Fe(II) polypyridines are an important class of pseudo-octahedral metal complexes
      known for their potential applications in molecular electronic switches, data
      storage and display devices, sensors, and dye-sensitized solar cells. Fe(II)
      polypyridines have a d(6) electronic configuration and pseudo-octahedral geometry
      and can therefore possess either a high-spin (quintet) or a low-spin (singlet)
      ground state. In this study, we investigate a series of complexes based on
      [Fe(tpy)2](2+) (tpy = 2,2';6',2"-terpyridine) and [Fe(dcpp)2](2+) (dcpp = 2,6
      bis(2-carboxypyridyl)pyridine). The ligand field strength in these complexes is
      systematically tuned by replacing the central pyridine with five-membered (N
      heterocyclic carbene, pyrrole, furan) or six-membered (aryl, thiazine-1,1
      dioxide, 4-pyrone) moieties. To determine the impact of ligand substitutions on
      the relative energies of metal-centered states, the singlet, triplet, and quintet
      states of the Fe(II) complexes were optimized in water (PCM) using density
      functional theory at the B3LYP+D2 level with 6-311G* (nonmetals) and SDD (Fe)
      basis sets. It was found that the dcpp ligand scaffold allows for a more ideal
      octahedral coordination environment in comparison to the tpy ligand scaffold. The
      presence of six-membered central rings also allows for a more ideally octahedral
      coordination environment relative to five-membered central rings, regardless of
      the ligand scaffold. We find that the ligand field strength in the Fe(II)
      polypyridines can be tuned by altering the donor atom identity, with C donor
      atoms providing the strongest ligand field. 

PMID- 26295276
TI  - Dyadic coping and relationship satisfaction: A meta-analysis.
AB  - Meta-analytic methods were used to empirically determine the association between
      dyadic coping and relationship satisfaction. Dyadic coping is a systemic
      conceptualization of the processes partners use to cope with stressors, such as
      stress communication, individual strategies to assist the other partner cope with
      stress, and partners' strategies to cope together. A total of 72 independent
      samples from 57 reports with a combined sum of 17,856 participants were included.
      The aggregated standardized zero-order correlation (r) for total dyadic coping
      with relationship satisfaction was .45 (p=.000). Total dyadic coping strongly
      predicted relationship satisfaction regardless of gender, age, relationship
      length, education level, and nationality. Perceptions of overall dyadic coping by
      partner and by both partners together were stronger predictors of relationship
      satisfaction than perceptions of overall dyadic coping by self. Aggregated
      positive forms of dyadic coping were a stronger predictor of relationship
      satisfaction than aggregated negative forms of dyadic coping. Comparisons among
      dyadic coping dimensions indicated that collaborative common coping, supportive
      coping, and hostile/ambivalent coping were stronger predictors of relationship
      satisfaction than stress communication, delegated coping, protective buffering
      coping, and overprotection coping. Clinical implications and recommendations for
      future research are provided. 

PMID- 26295277
TI  - A sensitive and selective LC-MS/MS method for the quantitative determination of
      segetalin A from the plasma of rats.
AB  - A sensitive and selective LC-MS/MS method was developed and validated for the
      determination and pharmacokinetic investigation of segetalin A in rat plasma.
      Sample preparation was accomplished through a simple SPE procedure for the
      removal and preconcentration of the analyte and IS. Plasma samples were separated
      by HPLC on a Symmetry C18 column using a mobile phase consisting of methanol and
      0.1% formic acid in water (70:30, v/v) with isocratic elution. The quantification
      was performed using multiple reaction monitoring with the transitions m/z 610.3 
      > 511.2 for segetalin A and m/z 779.4 -> 751.4 for IS, respectively. The
      calibration curve was linear over the range of 8.0-4000 ng/mL with a limit of
      quantitation (LOQ) of 8.0 ng/mL. This method was applied in a pharmacokinetic
      study of segetalin A in rats. For intravenous (i.v.) administration, the plasma
      concentrations of segetalin A decreased quickly (t1/2z, 1.31 +/- 0.341 h). For
      oral administration, the plasma concentrations of segetalin A increased to a peak
      value at 1.50 +/- 0.577 h, followed by a gradual decrease to the LOQ in 12 h. The
      mean AUC values after i.v. and oral administration were 553 +/- 105 and 1482 +/-
      110 ng h/mL, respectively.

PMID- 26295278
TI  - Improved proteomic analysis following trichloroacetic acid extraction of Bacillus
      anthracis spore proteins.
AB  - Proteomic analysis of bacterial samples provides valuable information about
      cellular responses and functions under different environmental pressures.
      Analysis of cellular proteins is dependent upon efficient extraction from
      bacterial samples, which can be challenging with increasing complexity and
      refractory characteristics. While no single method can recover 100% of the
      bacterial proteins, selected protocols can improve overall protein isolation,
      peptide recovery, or enrichment for certain classes of proteins. The method
      presented here is technically simple, does not require specialized equipment such
      as a mechanical disrupter, and is effective for protein extraction of the
      particularly challenging sample type of Bacillus anthracis Sterne spores. The
      ability of Trichloroacetic acid (TCA) extraction to isolate proteins from spores
      and enrich for spore-specific proteins was compared to the traditional mechanical
      disruption method of bead beating. TCA extraction improved the total average
      number of proteins identified within a sample as compared to bead beating (547 vs
      495, respectively). Further, TCA extraction enriched for 270 spore proteins,
      including those typically identified by first isolating the spore coat and
      exosporium layers. Bead beating enriched for 156 spore proteins more typically
      identified from whole spore proteome analyses. The total average number of
      proteins identified was equal using TCA or bead beating for easily lysed samples,
      such as B. anthracis vegetative cells. As with all assays, supplemental methods
      such as implementation of an alternative preparation method may simplify sample
      preparation and provide additional insight to the protein biology of the organism
      being studied. 

PMID- 26295279
TI  - Organically Modified Silica Nanoparticles Interaction with Macrophage Cells:
      Assessment of Cell Viability on the Basis of Physicochemical Properties.
AB  - Silica nanoparticles have drawn a lot of attention for nanomedicine application,
      and this is attributed to their biocompatibility and ease of surface
      functionalization. However, successful utilization of these inorganic systems for
      biomedical application depends on their physicochemical properties. This study,
      therefore, discusses in vitro toxicity of organically modified silica
      nanoparticles on the basis of size, shape, and surface properties of silica
      nanoparticles. Spherical- and oval-shaped nanoparticles having hydroxyl and amine
      groups were synthesized in Tween 80 micelles using different organosilanes.
      Nanoparticles of similar size and morphology were considered for comparative
      assessment. "As-prepared" nanoparticles were characterized in terms of size,
      shape, and surface properties using ZetaSizer, transmission electron microscopy,
      and Fourier transform infrared to establish the above parameters. In vitro
      analysis in terms of nanoparticle-based toxicity was performed on J-774
      (macrophage) cell line using propidium iodide-4',6-diamidino-2-phenylindol and 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Fluorescent
      dye-entrapped nanoparticles were used to visualize the uptake of the
      nanoparticles by macrophage cells. Results from cell studies suggested low levels
      of toxicity for different nanoparticle formulations studied, therefore are
      suitable for nanocarrier application for poorly soluble molecules. On the
      contrary, the nanoparticles of similar size and shape, having amine groups and
      low net negative charge, do not exhibit any in vitro cytotoxicity.

PMID- 26295280
TI  - Treatment of norovirus particles with citrate.
AB  - Human norovirus is a dominant cause of acute gastroenteritis around the world.
      Several norovirus disinfectants label citric acid as an active ingredient. In
      this study, we showed that norovirus virus-like particles (VLPs) treated with
      citrate buffer caused the particles to alter their morphology, including
      increased diameters associated with a new ring-like structure. We also found that
      epitopes on the protruding (P) domain on these particles were more readily
      accessible to antibodies after the citrate treatment. These results suggested
      that citrate had a direct effect on the norovirus particles. Using X-ray
      crystallography, we showed that the P domain bound citrate from lemon juice and a
      disinfectant containing citric acid. Importantly, citrate binds at the histo
      blood group antigen binding pocket, which are attachment factors for norovirus
      infections. Taken together, these new findings suggested that it might be
      possible to treat/reduce norovirus infections with citrate, although further
      studies are needed. 

PMID- 26295281
TI  - Evolution and function of the HCV NS3 protease in patients with acute hepatitis C
      and HIV coinfection.
AB  - Little is known about the importance of the hepatitis C virus (HCV) NS3 protease
      in acute hepatitis C. In this prospective study, 82 consecutive patients with
      acute hepatitis C and human immunodeficiency virus (HIV) coinfection were
      enrolled. Individuals were infected with highly related HCV strains and the
      baseline NS3 quasispecies diversity and complexity was higher compared to a
      chronic hepatitis C control group (P<0.0001). Both parameters were comparable in
      patients with spontaneous clearance (n=6) versus treatment-induced SVR (n=5) or
      development of chronic hepatitis C (n=9). Longitudinal NS3 quasispecies kinetics
      showed a trend to a decreasing diversity and complexity (P<0.05) within 4 weeks
      in patients with spontaneous clearance compared to the other groups. The innate
      immune signalling protein CARDIF was cleaved to a similar extent independent of
      the outcome. Together with a more pronounced viral load decline (P<0.05), an
      early decreasing NS3 quasispecies evolution indicates spontaneous clearance of
      acute hepatitis C. 

PMID- 26295282
TI  - Orienting to face expression during encoding improves men's recognition of own
      gender faces.
AB  - It is unclear why women have superior episodic memory of faces, but the benefit
      may be partially the result of women engaging in superior processing of facial
      expressions. Therefore, we hypothesized that orienting instructions to attend to
      facial expression at encoding would significantly improve men's memory of faces
      and possibly reduce gender differences. We directed 203 college students (122
      women) to study 120 faces under instructions to orient to either the person's
      gender or their emotional expression. They later took a recognition test of these
      faces by either judging whether they had previously studied the same person or
      that person with the exact same expression; the latter test evaluated
      recollection of specific facial details. Orienting to facial expressions during
      encoding significantly improved men's recognition of own-gender faces and
      eliminated the advantage that women had for male faces under gender orienting
      instructions. Although gender differences in spontaneous strategy use when
      orienting to faces cannot fully account for gender differences in face
      recognition, orienting men to facial expression during encoding is one way to
      significantly improve their episodic memory for male faces. 

PMID- 26295283
TI  - A DFT+U study of A-site and B-site substitution in BaFeO3-delta.
AB  - BaFeO3-delta (BFO)-based perovskites have emerged as cheap and effective oxygen
      electrocatalysts for oxygen reduction reaction at high temperatures. The BFO
      cubic phase facilitates a high oxygen deficiency and is commonly stabilised by
      partial substitution. Understanding the electronic mechanisms of substitution and
      oxygen deficiency is key to rational material design, and can be realised through
      DFT analysis. In this work an in-depth first principle DFT+U study is undertaken
      to determine site distinctive characteristics for 12.5%, Y, La and Ce
      substitutions in BFO. In particular, it is shown that B-site doped structures
      exhibit a lower energy cost for oxygen vacancy formation relative to A site
      doping and pristine BFO. This is attributed to the stabilisation of holes in the
      oxygen sub-lattice and increased covalency of the Fe-O bonds of the FeO6
      octahedra in B-site-substituted BFO. Charge analysis shows that A-site
      substitution amounts to donor doping and consequently impedes the accommodation
      of other donors (i.e. oxygen vacancies). However, A-site substitution may also
      exhibit a higher electronic conductivity due to less lattice distortion for
      oxygen deficiency compared to B-site doped structures. Furthermore, analysis of
      the local structural effects provides physical insight into stoichiometric
      expansions observed for this material. 

PMID- 26295284
TI  - Metamemory following childhood brain injury: A consequence of executive
      impairment.
AB  - In this study, we investigated the influence of children's level of executive
      functioning on two types of metamemory knowledge following a traumatic brain
      injury (TBI). For this purpose, 22 children (aged 7 to 14 years) who had
      sustained a moderate to severe TBI and 44 typically developing children were
      recruited. The children with TBI were divided into two groups according to the
      severity of their executive impairment. Injury severity was determined by the
      Glasgow Coma Scale (GCS) score on admission or by the duration of
      unconsciousness. All children were then tested on both their knowledge of general
      memory functioning and their level of memory self-awareness, respectively
      assessed using the total number of correct responses on an adapted version of a
      metamemory interview and a self-other discrepancy score on a questionnaire
      evaluating everyday memory abilities. Data analyses revealed that participants
      with TBI who suffered impaired executive functions demonstrated less general
      metamemory knowledge, and underestimated the frequency of their memory problems,
      compared with children with TBI who had preserved executive functions and with
      control participants. Considering the well-established effect of metamemory
      knowledge on people's spontaneous implementation of strategies, the interest and
      the importance of these findings on both theoretical and clinical grounds are
      discussed.

PMID- 26295285
TI  - Multicomponent Molecular Orbital-Climbing Image-Nudged Elastic Band Method to
      Analyze Chemical Reactions Including Nuclear Quantum Effect.
AB  - To analyze the H/D isotope effects on hydrogen transfer reactions in XHCHCHCHY<
      >XCHCHCHYH (X, Y=O, NH, or CH2 ) including the nuclear quantum effect of proton
      and deuteron, we propose a multicomponent molecular orbital-climbing image-nudged
      elastic band (MC_MO-CI-NEB) method. We obtain not only transition state
      structures but also minimum-energy paths (MEPs) on the MC_MO effective potential
      energy surface by using MC_MO-CI-NEB method. We find that nuclear quantum effect
      affects not only stationary-point geometries but also MEPs and electronic
      structures in the reactions. We clearly demonstrate the importance of including
      nuclear quantum effects for H/D isotope effect on rate constants (kH /kD ). 

PMID- 26295286
TI  - Identification of Phenoxyalkylbenzimidazoles with Antitubercular Activity.
AB  - We conducted an evaluation of the phenoxyalkylbenzimidazole series based on the
      exemplar 2-ethyl-1-(3-phenoxypropyl)-1H-benzo[d]imidazole for its antitubercular
      activity. Four segments of the molecule were examined systematically to define a
      structure-activity relationship with respect to biological activity. Compounds
      had submicromolar activity against Mycobacterium tuberculosis; the most potent
      compound had a minimum inhibitory concentration (MIC) of 52 nM and was not
      cytotoxic against eukaryotic cells (selectivity index = 523). Compounds were
      selective for M. tuberculosis over other bacterial species, including the closely
      related Mycobacterium smegmatis. Compounds had a bacteriostatic effect against
      aerobically grown, replicating M. tuberculosis, but were bactericidal against
      nonreplicating bacteria. Representative compounds had moderate to high
      permeability in MDCK cells, but were rapidly metabolized in rodents and human
      liver microsomes, suggesting the possibility of rapid in vivo hepatic clearance
      mediated by oxidative metabolism. These results indicate that the readily
      synthesized phenoxyalkylbenzimidazoles are a promising class of potent and
      selective antitubercular agents, if the metabolic liability can be solved. 

PMID- 26295287
TI  - Catalytic Asymmetric Oxidative alpha-C-H N,O-Ketalization of Ketones by Chiral
      Primary Amine.
AB  - A highly enantioselective primary amine catalyzed alpha,alpha-bis
      functionalization of beta-ketocarbonyls and cyclohexanones is described. This
      transformation employs N-hydroxycarbamates as both nitrogen and oxygen sources
      under aerobic oxidative conditions to furnish chiral N,O-ketals with high yields
      and enantioselectivities. 

PMID- 26295290
TI  - Chemical composition of various Ephedra species.
AB  - The medicinal significance of Ephedra is based on the sympathomimetic properties
      of ephedrine (E) alkaloids. Pharmacological effects depend on the
      phytocomposition of individual Ephedra species. The aim of this study was to
      measure the total alkaloids content (TAC), total phenolics content (TPC), and
      total flavonoids content (TFC) and determine their relationship in dry herb of
      Ephedra major, Ephedra distachya subsp. helvetica, Ephedra monosperma, Ephedra
      fragilis, Ephedra foeminea, Ephedra alata, Ephedra altissima and Ephedra foliata.
      Nowadays, medicinal use of Ephedrae herba is limited, but the abuse of its
      psychostimulants is rising. In this study, TAC, TPC and TFC were determined using
      spectrophotometric methods. For the first time, ultra-performance liquid
      chromatography with ultraviolet detection (UPLC-UV) was used for separation and
      quantification of E-type alkaloids of various Ephedra species. The highest TPC
      and TFC were found in E. alata (53.3 +/- 0.1 mg Gallic acid equivalents/g dry
      weight, 2.8 mg quercetin equivalents/g dry weight, respectively). The total
      content of E and pseudoephedrine determined by UPLC-UV varied between 20.8 mg/g
      dry weight (E. distachya subsp. helvetica) and 34.7 mg/g dry weight (E.
      monosperma). The variable content and ratio between secondary metabolites
      determined in different Ephedra species reflects their metabolic activities.
      Utilization of UPLC-UV unveiled that this technique is sensitive, selective, and
      useful for separation and quantification of different alkaloids in complex
      biological matrixes. The limit of detection was 5 ng. Application of UPLC-UV can
      be recommended in quick analyses of E-type alkaloids in forensic medicine and
      quality control of pharmaceutical preparations. 

PMID- 26295288
TI  - Lyme Borreliosis: Is there a preexisting (natural) variation in antimicrobial
      susceptibility among Borrelia burgdorferi strains?
AB  - The development of antibiotics changed the world of medicine and has saved
      countless human and animal lives. Bacterial resistance/tolerance to antibiotics
      have spread silently across the world and has emerged as a major public health
      concern. The recent emergence of pan-resistant bacteria can overcome virtually
      any antibiotic and poses a major problem for their successful control. Selection
      for antibiotic resistance may take place where an antibiotic is present: in the
      skin, gut, and other tissues of humans and animals and in the environment.
      Borrelia burgdorferi, the etiological agents of Lyme borreliosis, evades host
      immunity and establishes persistent infections in its mammalian hosts. The
      persistent infection poses a challenge to the effective antibiotic treatment, as
      demonstrated in various animal models. An increasingly heterogeneous
      subpopulation of replicatively attenuated spirochetes arises following treatment,
      and these persistent antimicrobial tolerant/resistant spirochetes are non
      cultivable. The non-cultivable spirochetes resurge in multiple tissues at 12
      months after treatment, with B. burgdorferi-specific DNA copy levels nearly
      equivalent to those found in shame-treated experimental animals. These attenuated
      spirochetes remain viable, but divide slowly, thereby being tolerant to
      antibiotics. Despite the continued non-cultivable state, RNA transcription of
      multiple B. burgdorferi genes was detected in host tissues, spirochetes were
      acquired by xenodiagnostic ticks, and spirochetal forms could be visualized
      within ticks and mouse tissues. A number of host cytokines were up- or down
      regulated in tissues of both shame- and antibiotic-treated mice in the absence of
      histopathology, indicating a lack of host response to the presence of
      antimicrobial tolerant/resistant spirochetes. 

PMID- 26295291
TI  - Detailed polymorphism study on cytomegalovirus DNA polymerase gene to reveal the
      most suitable genomic targets for quantitative Real-time PCR.
AB  - The human cytomegalovirus (HCMV) is an important human pathogen primarily
      affecting immunocompromised patients, like transplant recipients or HIV- infected
      individuals. Early diagnosis of cytomegalovirus (CMV) infection in high-risk
      patients is essential in order to start preemptive treatments. pol (UL54) gene
      encoding for HCMV viral DNA polymerase is a well-defined target for HCMV
      detection in clinical samples and identifying most highly conserved regions for
      primer design remains crucial. Though real-time polymerase chain reaction (qPCR)
      is a rapid and sensitive method for HCMV detection, failure to detect some HCMV
      strains due to primer and target mismatches have led the researchers to explore
      more sensitive and reliable methods. Hence, to understand the broader diversity
      of the pol mutations in HCMV and to specify the most suitable region for primer
      probe design to be used in qPCR assay, we studied both nucleotide and amino acid
      heterogeneities in 60 HCMV positive samples that were collected to represent
      national mutational prevalence of pol gene of HCMV in Turkey. The test was
      designed with a new set of primers- probe for HCMV detection and quantification
      based on the sequencing data which revealed the most conserved region on the pol
      gene. Statistical probit analysis was applied on qPCR studies which revealed a
      95% detection limit of 100 copies/mL. In addition, linearity, reproducibility,
      and precision of the new test were assessed for diagnostic purposes. 

PMID- 26295289
TI  - Dystrophin and the two related genetic diseases, Duchenne and Becker muscular
      dystrophies.
AB  - Mutations of the dystrophin DMD gene, essentially deletions of one or several
      exons, are the cause of two devastating and to date incurable diseases, Duchenne
      (DMD) and Becker (BMD) muscular dystrophies. Depending upon the preservation or
      not of the reading frame, dystrophin is completely absent in DMD, or present in
      either a mutated or a truncated form in BMD. DMD is a severe disease which leads
      to a premature death of the patients. Therapy approaches are evolving with the
      aim to transform the severe DMD in the BMD form of the disease by restoring the
      expression of a mutated or truncated dystrophin. These therapies are based on the
      assumption that BMD is a mild disease. However, this is not completely true as
      BMD patients are more or less severely affected and no molecular basis of this
      heterogeneity of the BMD form of the disease is yet understood. The aim of this
      review is to report for the correlation between dystrophin structures in BMD
      deletions in view of this heterogeneity and to emphasize that examining BMD
      patients in details is highly relevant to anticipate for DMD therapy effects. 

PMID- 26295292
TI  - Prevalence and genotype distribution of rotaviruses in children with
      gastroenteritis in Rize province.
AB  - Determination of the distribution of rotavirus genotypes is essential for
      understanding the epidemiology of this virus responsible for nearly half a
      million of deaths in patients with gastroenteritis worldwide. In the present
      study, we aimed to genotype the rotavirus strains isolated from diarrheal stool
      samples in children under 5 years old. A total of 1297 fecal samples were
      collected, and rotavirus antigen was detected in 73 of these samples. Antigen
      positive samples were transferred to the Public Health Agency of Turkey,
      Molecular Microbiology Research Laboratory, and were tested for determination of
      genotypes G and P using semi-nested multiplex polymerase chain reaction method
      performed with consensus- and genotype-specific primers. Twelve specimens were
      found to be negative for rotavirus in genotyping method. All the positive-strains
      were in G1-4, G8-9, P(4), P(8), and P(9) genotypes. The most frequent GP genotype
      combinations were found to be G9P(8) in 21 strains (34.4%), G2P(4) in 14 strains
      (23.0%), and G1P(8) in 12 strains (19.7%). We found 10 distinct genotypes amongst
      a total of 61 strains. Among the strains isolated and genotyped in our study,
      90.2% (55/61) and 67.2% (41/61) have already been included in the two existing
      commercial vaccines. In conclusion, these findings implicate the necessity of
      development of region-specific vaccines after evaluation of the local genotype
      distribution. Further studies on the large number of rotavirus strains would
      contribute to this process. 

PMID- 26295293
TI  - Investigating the presence of fungal agents in febrile neutropenic patients using
      different microbiological, serological, and molecular methods.
AB  - This study aimed to investigate fungal agents in febrile neutropenic patients
      with hematological malignancies. Direct microscopy and cultures were performed on
      clinical samples collected from febrile neutropenic episodes. The galactomannan
      (GM) antigen was tested using enzyme-linked immunosorbent assays, and Aspergillus
      fumigatus and Candida albicans deoxyribonucleic acid (DNA) assessed using real
      time polymerase chain reaction (PCR) in consecutive serum samples. Of the 199
      episodes investigated, 1.5% were classified as definite invasive aspergillosis
      (IA), 4.0% as IA with high probability, and 4.0% as IA with low probability.
      Additionally, candidaemia was detected in eight episodes (4.1%). The GM antigen
      was found negative for 86.4% of episodes, as one positive for 7.0% of episodes,
      as two or more consecutive positives for 5.5% of episodes, and as positive in any
      two serum samples in 1.0% of episodes. While no C. albicans DNA was detected in
      98.5% of 199 episodes, one positive result was obtained in 1.0% of episodes, and
      two or more consecutive positives in 0.5% of episodes. A. fumigatus PCR results
      were found negative in 81.9% of episodes, as one positive in 16.1% of episodes,
      as positive in any two serum samples in 1.0% of episodes, and consecutively
      positive in 1.0% of episodes. GM antigen tests were found consecutively positive
      in all three patients diagnosed as having definite IA. These findings indicate
      that conventional, serological, and molecular methods should be used in
      combination to detect fungal agents in febrile neutropenic patients. 

PMID- 26295294
TI  - Genotypic and phenotypic characteristics of Methicillin-resistant Staphylococcus
      aureus (MRSA) strains, isolated on three different geography locations.
AB  - Staphylococcus aureus is a major cause of hospital-acquired infections worldwide.
      Increased frequency of methicillin-resistant Staphylococcus aureus (MRSA) in
      hospitalized patients and possibility of vancomycin resistance requires rapid and
      reliable characterization of isolates and control of MRSA spread in hospitals.
      Typing of isolates helps to understand the route of a hospital pathogen spread.
      The aim of this study was to investigate and compare genotypic and phenotypic
      characteristics of MRSA samples on three different geography locations. In
      addition, our aim was to evaluate three different methods of MRSA typing: spa
      typing, agr-typing and GenoType MRSA.  We included 104 samples of MRSA, isolated
      in 3 different geographical locations in clinical hospitals in Zagreb, Mostar,
      and Heidelberg, during the period of six months. Genotyping and phenotyping were
      done by spa-typing, agr-typing and dipstick assay GenoType MRSA. We failed to
      type all our samples by spa-typing.  The most common spa-type in clinical
      hospital Zagreb was t041, in Mostar t001, and in Heidelberg t003.We analyzed
      102/104 of our samples by agr-typing method. We did not find any agr-type IV in
      our locations. We analyzed all our samples by the dipstick assay GenoType MRSA.
      All isolates in our study were MRSA strains. In Zagreb there were no positive
      strains to PVL gene. In Mostar we have found 5/25 positive strains to PVL gene,
      in Heidelberg there was 1/49. PVL positive isolates were associated with spa-type
      t008 and agr-type I, thus, genetically, they were community-associated MRSA (CA
      MRSA). Dipstick assay GenoType MRSA has demonstrated sufficient specificity,
      sensibility, simple performance and low cost, so we could introduce it to work in
      smaller laboratories. Using this method may expedite MRSA screening, thus
      preventing its spread in hospitals. 

PMID- 26295295
TI  - Nesfatin-1 and Vitamin D levels may be associated with systolic and diastolic
      blood pressure values and hearth rate in polycystic ovary syndrome.
AB  - Obesity, insulin resistance (IR), inflammation, and hyperandrogenism may lead to
      polycystic ovary syndrome (PCOS) and hypertension. Nesfatin-1 (N1) may be related
      to IR, obesity, and hypertension. Furthermore, a vitamin D (VD) deficiency is
      associated with hypertension and PCOS. We aimed to investigate N1 and VD levels
      in PCOS that have an effect on systolic and diastolic blood pressure (BP) and
      heart rate (HR).This study included 54 patients with PCOS and 48 age-body mass
      index (BMI)-matched healthy controls. PCOS was diagnosed according to clinical
      practice guidelines. Ferriman-Gallwey scores (FGS) were calculated, while N1, VD,
      and other hormonal and biochemical parameters were measured for all subjects.
      Systolic and diastolic BP was measured as well. HR was calculated using an
      electrocardiogram.The levels of N1 (p < 0.001), high-sensitivity C-reactive
      protein (hs-CRP) (p = 0.036), homeostasis model assessment as an index of insulin
      resistance (HOMA-IR) (p < 0.001), systolic (p < 0.001) and diastolic (p < 0.001)
      BP and HR (p < 0.001) in the PCOS group were significantly higher than in the
      control group. However, the VD levels of the PCOS group were lower than the
      control group (p = 0.004). N1 had a strong positive correlation with BMI, HOMA
      IR, hs-CRP, luteinizing hormone, systolic and diastolic BP, and HR. VD levels
      were negatively correlated with HOMA-IR and luteinizing hormone.Elevated N1 and
      decreased VD levels may be related to the presence of high-normal BP or
      hypertension in PCOS subjects.  N1 level may be associated with an increased BP
      due to its relation to inflammation and IR. 

PMID- 26295296
TI  - Demographic, clinical, and laboratory features of Turkish patients with late
      onset ankylosing spondylitis.
AB  - Ankylosing spondylitis (AS) is a chronic inflammatory disease, which typically
      begins in early decades of life with primarily axial joints involvement. This
      disease rarely affects patients older than 50 years of age. The aim of this study
      was to compare and evaluate the demographic, clinical, and laboratory features of
      late onset and early onset AS patients who were followed up in a single
      rheumatology center. A total of 339 patients who have been diagnosed with AS
      according to modified New York criteria were included in the study. The patients
      whose initial symptoms were observed after 50 years of age were accepted as late
      onset AS. Out of 339 patients, 27 (7.9%) were diagnosed as late onset AS and 312
      (92.3%) patients were evaluated as early onset AS. Of 27 late onset patients, 10
      were male and 17 were female. Delay in the diagnosis was 5.8 years for early
      onset AS, while it was 3.8 years for late onset AS (p = 0.001). Higher levels of
      acute phase reactants and more methotrexate (MTX) use were detected in early
      onset AS patients compared to late onset AS (p = 0.001, p = 0.007, respectively).
      Statistically, there was no difference between these two groups, with regard to
      disease clinical activity indexes, anthropometric measurement parameters, uveitis
      and peripheral joint involvement. In this study, we showed that early and late
      onset AS patients may present with different clinical, genetic, and laboratory
      features. Late onset AS patients are characterized with lower human leukocyte
      antigen-B27 sequence, less inflammatory sign, delayed diagnosis, and less MTX and
      anti-tumor necrosis factor alpha drug usage. 

PMID- 26295297
TI  - Cardiotrophin-1: A new predictor of atrial fibrillation relapses after successful
      cardioversion.
AB  - We aimed to investigate whether or not cardiotrophin-1 (CT-1) can be used as a
      predictor of sinus rhythm constancy in patients with atrial fibrillation (AF)
      converted to sinus rhythm. Thirty two patients with AF (48-78 years), without any
      structural heart disease were enrolled for the study. The control group consisted
      of 32, age and gender matched healthy persons. Measurements of CT-1 were made
      after transthoracic and transesophageal echocardiography prior to cardioversion
      (CV). Relapses of AF were investigated by monthly electrocardiograms (ECGs) and
      ambulatory ECGs at 1st, 3rd, and 6th month. At the end of 6th month, measurements
      of CT-1 were repeated. At the beginning patients with AF had increased CT-1
      levels when compared to controls (0.94 +/- 0.32 pg/mL vs. 0.30 +/- 0.12 pg/mL, [p
      < 0.001]). At the end of follow-up of the 32 patients, 17 (53%) had AF relapse.
      Age, initial duration of AF, left ventricle diameters, ejection fraction, left
      atrium appendix flow rates were similar among patients with and without AF
      relapse. However, basal left atrium diameter (4.24 +/- 0.14 cm vs. 4.04 +/- 0.22
      cm, p = 0.005), pulmonary artery pressure (32.82 +/- 5 vs. 28.60 +/- 6.23 mmHg, p
      = 0.004) and CT-1 values (1.08 +/- 0.37 vs. 0.82 +/- 0.16 pg/mL, p = 0.02) were
      significantly increased in patients with AF relapse. Furthermore, patients with
      relapsed AF had higher CT-1 levels at 6th month when compared to those in sinus
      rhythm (1.00 +/- 0.40 vs. 0.71 +/- 0.23 pg/mL). We conclude that post-CV, AF
      relapses are more frequent among patients with increased baseline CT-1 levels,
      and CT-1 may be a potential predictor of AF relapse. 

PMID- 26295298
TI  - Effect of clozapine on locomotor activity and anxiety-related behavior in the
      neonatal mice administered MK-801.
AB  - Atypical antipsychotics have been used to treat fear and anxiety disturbance that
      are highly common in schizophrenic patients. It is suggested that disruptions of
      N-methyl-d-aspartate (NMDA)-mediated transmission of glutamate may underlie the
      pathophysiology of schizophrenia. The present study was conducted to analyze the
      effectiveness of clozapine on the anxiety-related behavior and locomotor function
      of the adult brain, which had previously undergone NMDA receptor blockade during
      a developmental period. In order to block the NMDA receptor, male mice were
      administered 0.25 mg/kg of MK-801 on days 7 to 10 postnatal. In adulthood, they
      were administered intraperitoneally 0.5 mg/kg of clozapine and tested with open
      field and elevated plus maze test, to assess their emotional behavior and
      locomotor activity. In the group receiving MK-801 in the early developmental
      period the elevated plus maze test revealed a reduction in the anxiety-related
      behavior (p<0.05), while the open-field test indicated a decrease in locomotor
      activity (p<0.01). Despite these reductions, clozapine could not reverse the NMDA
      receptor blockade. Also, as an atypical antipsychotic agent, clozapine could not
      reverse impairment in the locomotor activity and anxiety-related behavior,
      induced by administration of the MK-801 in neonatal period. 

PMID- 26295299
TI  - Comment on "Structural changes in the rat placenta during the last third of
      gestation discovered by stereology".

PMID- 26295300
TI  - Reply to comment on "Structural changes in the rat placenta during the last third
      of gestation discovered by stereology".

PMID- 26295301
TI  - Clinical Neuropathology 5-2015.

PMID- 26295303
TI  - Magnetically driven medical devices: a review.
AB  - A widely accepted definition of a medical device is an instrument or apparatus
      that is used to diagnose, prevent or treat disease. Medical devices take a broad
      range of forms and utilize various methods to operate, such as physical,
      mechanical or thermal. Of particular interest in this paper are the medical
      devices that utilize magnetic field sources to operate. The exploitation of
      magnetic fields to operate or drive medical devices has become increasingly
      popular due to interesting characteristics of magnetic fields that are not
      offered by other phenomena, such as mechanical contact, hydrodynamics and
      thermodynamics. Today, there is a wide range of magnetically driven medical
      devices purposed for different anatomical regions of the body. A review of these
      devices is presented and organized into two groups: permanent magnetically driven
      devices and electromagnetically driven devices. Within each category, the
      discussion will be further segregated into anatomical regions (e.g.,
      gastrointestinal, ocular, abdominal, thoracic, etc.). 

PMID- 26295302
TI  - Clinical Neuropathology practice guide 5-2015: MGMT methylation pyrosequencing in
      glioblastoma: unresolved issues and open questions.
AB  - O6-methylguanine-methyltransferase (MGMT) promoter methylation status has
      prognostic and, in the subpopulation of elderly patients, predictive value in
      newly diagnosed glioblastoma. Therefore, knowledge of the MGMT promoter
      methylation status is important for clinical decision-making. So far, MGMT
      testing has been limited by the lack of a robust test with sufficiently high
      analytical performance. Recently, one of several available pyrosequencing
      protocols has been shown to be an accurate and robust method for MGMT testing in
      an intra- and interlaboratory ring trial. However, some uncertainties remain with
      regard to methodological issues, cut-off definitions, and optimal use in the
      clinical setting. In this article, we highlight and discuss several of these open
      questions. The main unresolved issues are the definition of the most relevant CpG
      sites to analyze for clinical purposes and the determination of a cut-off value
      for dichotomization of quantitative MGMT pyrosequencing results into "MGMT
      methylated" and "MGMT unmethylated" patient subgroups as a basis for further
      treatment decisions. 

PMID- 26295304
TI  - Structural Insight into Multivalent Galactoside Binding to Pseudomonas aeruginosa
      Lectin LecA.
AB  - Multivalent galactosides inhibiting Pseudomonas aeruginosa biofilms may help
      control this problematic pathogen. To understand the binding mode of tetravalent
      glycopeptide dendrimer GalAG2 [(Gal-beta-OC6H4CO-Lys-Pro-Leu)4(Lys-Phe-Lys
      Ile)2Lys-His-Ile-NH2] to its target lectin LecA, crystal structures of LecA
      complexes with divalent analog GalAG1 [(Gal-beta-OC6H4CO-Lys-Pro-Leu)2Lys-Phe-Lys
      Ile-NH2] and related glucose-triazole linked bis-galactosides 3u3 [Gal-beta
      O(CH2)n-(C2HN3)-4-Glc-beta-(C2HN3)-[beta-Glc-4-(N3HC2)]2-(CH2)n-O-beta-Gal (n =
      1)] and 5u3 (n = 3) were obtained, revealing a chelate bound 3u3, cross-linked
      5u3, and monovalently bound GalAG1. Nevertheless, a chelate bound model better
      explaining their strong LecA binding and the absence of lectin aggregation was
      obtained by modeling for all three ligands. A model of the chelate bound
      GalAG2.LecA complex was also obtained rationalizing its unusually tight LecA
      binding (KD = 2.5 nM) and aggregation by lectin cross-linking. The very weak
      biofilm inhibition with divalent LecA inhibitors suggests that lectin aggregation
      is necessary for biofilm inhibition by GalAG2, pointing to multivalent
      glycoclusters as a unique opportunity to control P. aeruginosa biofilms. 

PMID- 26295305
TI  - Non genomic loss of function of tumor suppressors in CML: BCR-ABL promotes
      IkappaBalpha mediated p53 nuclear exclusion.
AB  - Tumor suppressor function can be modulated by subtle variation of expression
      levels, proper cellular compartmentalization and post-translational
      modifications, such as phosphorylation, acetylation and sumoylation. The non
      genomic loss of function of tumor suppressors offers a challenging therapeutic
      opportunity. The reactivation of a tumor suppressor could indeed promote
      selective apoptosis of cancer cells without affecting normal cells. The
      identification of mechanisms that affect tumor suppressor functions is therefore
      essential. In this work, we show that BCR-ABL promotes the accumulation of the
      NFKBIA gene product, IkappaBalpha, in the cytosol through physical interaction
      and stabilization of the protein. Furthermore, BCR-ABL/IkappaBalpha complex acts
      as a scaffold protein favoring p53 nuclear exclusion. We therefore identify a
      novel BCR-ABL/IkappaBalpha/p53 network, whereby BCR-ABL functionally inactivates
      a key tumor suppressor. 

PMID- 26295306
TI  - Combined expressional analysis, bioinformatics and targeted proteomics identify
      new potential therapeutic targets in glioblastoma stem cells.
AB  - Glioblastoma (GBM) is both the most common and the most lethal primary brain
      tumor. It is thought that GBM stem cells (GSCs) are critically important in
      resistance to therapy. Therefore, there is a strong rationale to target these
      cells in order to develop new molecular therapies.To identify molecular targets
      in GSCs, we compared gene expression in GSCs to that in neural stem cells (NSCs)
      from the adult human brain, using microarrays. Bioinformatic filtering identified
      20 genes (PBK/TOPK, CENPA, KIF15, DEPDC1, CDC6, DLG7/DLGAP5/HURP, KIF18A, EZH2,
      HMMR/RHAMM/CD168, NOL4, MPP6, MDM1, RAPGEF4, RHBDD1, FNDC3B, FILIP1L, MCC,
      ATXN7L4/ATXN7L1, P2RY5/LPAR6 and FAM118A) that were consistently expressed in GSC
      cultures and consistently not expressed in NSC cultures. The expression of these
      genes was confirmed in clinical samples (TCGA and REMBRANDT). The first nine
      genes were highly co-expressed in all GBM subtypes and were part of the same
      protein-protein interaction network. Furthermore, their combined up-regulation
      correlated negatively with patient survival in the mesenchymal GBM subtype. Using
      targeted proteomics and the COGNOSCENTE database we linked these genes to GBM
      signalling pathways.Nine genes: PBK, CENPA, KIF15, DEPDC1, CDC6, DLG7, KIF18A,
      EZH2 and HMMR should be further explored as targets for treatment of GBM. 

PMID- 26295310
TI  - Dislocation-Mediated Deformation in Solid Langmuir Monolayers: Plastic Bending
      and Tilt Boundary.
AB  - The shear response of three types of textures (mosaic, striation, and stripe) in
      10,12-pentacosadiynoic acid solid Langmuir monolayers has been investigated with
      Brewster angle microscopy. Low temperature mosaic textures respond to an applied
      stress elastically. Upon the application of shear the change of contrast appears
      in the form of propagation of fronts roughly perpendicularly to the shear
      direction within a single domain reversibly, while the domain shape keeps
      constant since it is presumably frozen kinetically. The striation and stripe
      textures at high temperatures show a viscoplastic behavior (plastic bending) in
      its rheological response, being consistent with the formation of a dislocation
      wall (tilt boundary) through dislocation dynamics (dislocation glide and climb).
      The stress-induced formation of a tilt boundary provides a manifestation of the
      collective motion of a number of dislocations. 

PMID- 26295307
TI  - The 26S proteasome is a multifaceted target for anti-cancer therapies.
AB  - Proteasomes play a critical role in the fate of proteins that are involved in
      major cellular processes, including signal transduction, gene expression, cell
      cycle, replication, differentiation, immune response, cellular response to
      stress, etc. In contrast to non-specific degradation by lysosomes, proteasomes
      are highly selective and destroy only the proteins that are covalently labelled
      with small proteins, called ubiquitins. Importantly, many diseases, including
      neurodegenerative diseases and cancers, are intimately connected to the activity
      of proteasomes making them an important pharmacological target. Currently, the
      vast majority of inhibitors are aimed at blunting the proteolytic activities of
      proteasomes. However, recent achievements in solving structures of proteasomes at
      very high resolution provided opportunities to design new classes of small
      molecules that target other physiologically-important enzymatic activities of
      proteasomes, including the de-ubiquitinating one. This review attempts to catalog
      the information available to date about novel classes of proteasome inhibitors
      that may have important pharmacological ramifications. 

PMID- 26295308
TI  - The clinical development candidate CCT245737 is an orally active CHK1 inhibitor
      with preclinical activity in RAS mutant NSCLC and Eu-MYC driven B-cell lymphoma.
AB  - CCT245737 is the first orally active, clinical development candidate CHK1
      inhibitor to be described. The IC50 was 1.4 nM against CHK1 enzyme and it
      exhibited>1,000-fold selectivity against CHK2 and CDK1. CCT245737 potently
      inhibited cellular CHK1 activity (IC50 30-220 nM) and enhanced gemcitabine and
      SN38 cytotoxicity in multiple human tumor cell lines and human tumor xenograft
      models. Mouse oral bioavailability was complete (100%) with extensive tumor
      exposure. Genotoxic-induced CHK1 activity (pS296 CHK1) and cell cycle arrest
      (pY15 CDK1) were inhibited both in vitro and in human tumor xenografts by
      CCT245737, causing increased DNA damage and apoptosis. Uniquely, we show
      CCT245737 enhanced gemcitabine antitumor activity to a greater degree than for
      higher doses of either agent alone, without increasing toxicity, indicating a
      true therapeutic advantage for this combination. Furthermore, development of a
      novel ELISA assay for pS296 CHK1 autophosphorylation, allowed the quantitative
      measurement of target inhibition in a RAS mutant human tumor xenograft of NSCLC
      at efficacious doses of CCT245737. Finally, CCT245737 also showed significant
      single-agent activity against a MYC-driven mouse model of B-cell lymphoma. In
      conclusion, CCT245737 is a new CHK1 inhibitor clinical development candidate
      scheduled for a first in man Phase I clinical trial, that will use the novel
      pS296 CHK1 ELISA to monitor target inhibition.

PMID- 26295309
TI  - Neuroprotective effect of cellular prion protein (PrPC) is related with
      activation of alpha7 nicotinic acetylcholine receptor (alpha7nAchR)-mediated
      autophagy flux.
AB  - Activation of the alpha7 nicotinic acetylcholine receptor (alpha7nAchR) is
      regulated by prion protein (PrPC) expression and has a neuroprotective effect by
      modulating autophagic flux. In this study, we hypothesized that PrPC may regulate
      alpha7nAchR activation and that may prevent prion-related neurodegenerative
      diseases by regulating autophagic flux. PrP(106-126) treatment decreased
      alpha7nAchR expression and activation of autophagic flux. In addition, the
      alpha7nAchR activator PNU-282987 enhanced autophagic flux and protected neuron
      cells against PrP(106-126)-induced apoptosis. However, activation of autophagy
      and the protective effects of PNU-282987 were inhibited in PrPC knockout
      hippocampal neuron cells. In addition, PrPC knockout hippocampal neuron cells
      showed decreased alpha7nAchR expression levels. Adenoviral overexpression of PrPC
      in PrPC knockout hippocampal neuron cells resulted in activation of autophagic
      flux and inhibition of prion peptide-mediated cell death via alpha7nAchR
      activation. This is the first report demonstrating that activation of alpha7nAchR
      mediated autophagic flux is regulated by PrPC, and that activation of alpha7nAchR
      regulated by PrPC expression may play a pivotal role in protection of neuron
      cells against prion peptide-induced neuron cell death by autophagy. These results
      suggest that alpha7nAchR-mediated autophagic flux may be involved in the
      pathogenesis of prion-related diseases and may be a therapeutic target for prion
      related neurodegenerative diseases. 

PMID- 26295312
TI  - Independent Tuning of the Band Gap and Redox Potential of Graphene Quantum Dots.
AB  - The band gap and redox potential of semiconductor nanocrystals are two quantities
      of primary importance for their applications in energy conversion devices.
      Herein, we report on covalent functionalization of colloidal graphene quantum
      dots through a solution-chemistry approach and studies of their band gaps and
      redox potentials. We show that their band gaps and redox potentials can be
      independently controlled, the former by size and the latter by functionalization.
      The size and the functionalization dependence of the properties can be
      numerically reproduced with tight-binding calculations, which thus provides a
      simple theoretical tool to guide the design of graphene QDs with desired
      properties. 

PMID- 26295311
TI  - Fullerene-Grafted Graphene for Efficient Bulk Heterojunction Polymer Photovoltaic
      Devices.
AB  - A simple lithiation reaction was developed to covalently attach monosubstituted
      C60 onto graphene nanosheets. Detailed spectroscopic (e.g., Fourier transform
      infrared, Raman) analyses indicated that C60 molecules were covalently attached
      onto the graphene surface through monosubstitution. Transmission electron
      microscopic (TEM) observation revealed that these monosubstituted C60 moieties
      acted as nucleation centers to promote the formation of C60 aggregates of ~5 nm
      in diameter on the graphene surface. The resultant C60-grafted graphene
      nanosheets were used as electron acceptors in poly(3-hexylthiophene)-based bulk
      heterojunction solar cells to significantly improve the electron transport, and
      hence the overall device performance, yielding a power conversion efficiency of
      ~1.22%. 

PMID- 26295313
TI  - Resolving the Mystery of the Elusive Peak: Negative Differential Resistance in
      Redox Proteins.
AB  - Vertical molecular transistors are used to explain the nonconformal electron
      transfer results obtained for redox proteins. The transport characteristics of a
      negative differential resistance peak as appears in the transport data of azurin
      and its nonredox derivative are explored. A correlation between the peak and its
      redox center is demonstrated. 

PMID- 26295314
TI  - First-Principles Study of Lithium Borocarbide as a Cathode Material for
      Rechargeable Li ion Batteries.
AB  - Computational simulations within density functional theory are performed to
      investigate the potential application of a lithium borocarbide (LiBC) compound as
      a unique material for lithium ion batteries. The graphene-like BC sheets are
      predicted to be Li(+) intercalation hosts with the Li ion capacity surprisingly
      surpassing that of graphite. Here, the layered LixBC structure is preserved with
      x >= 0.5, indicating that half of the Li ions in the LiBC compound are
      rechargeable. Furthermore, the intercalation potential (equilibrium lithium
      insertion voltage of 2.3-2.4 V relative to lithium metal) is significantly higher
      than that in graphite, allowing Li0.5BC to function as a cathode material. The
      reversible electrochemical reaction, LiBC ? Li0.5BC + 0.5Li, enables a specific
      energy density of 1088 W h/kg and a volumetric energy density of 2463 W h/L. The
      volume change is less than 3% during the charging and discharging process. This
      discovery could lead to the development of a unique high-capacity LiBC Li ion
      cathode material. 

PMID- 26295315
TI  - Optimizing Nucleus Size Metrics for Liquid-Solid Nucleation from Transition Paths
      of Near-Nanosecond Duration.
AB  - We determine the mechanism for the liquid-solid phase transition in the Lennard
      Jones fluid close to coexistence with aimless shooting and likelihood
      maximization. The reaction coordinate for this process is a product of a
      structural descriptor and the size of the nascent solid nucleus and is
      quantitatively verified with the committor probability histogram test. This study
      identifies the first accurate scalar reaction coordinate for the liquid-solid
      nucleation process in Lennard-Jonesium, which will likely extend to nucleation
      processes in other spherically symmetric fluids. On the basis of our results, we
      propose a structural correction factor for the commonly cited nucleus size
      reaction coordinate from classical nucleation theory that enables connection of
      simulation data to stochastic models of nucleation kinetics. In addition, we show
      that aimless shooting is able to obtain reasonable acceptance rates for
      transitions with highly diffusive characteristics, which has been problematic for
      transition path sampling methods for diffusive processes such as nucleation and
      macromolecular transitions. 

PMID- 26295316
TI  - Chemical Reaction Dynamics in Liquid Solutions.
AB  - The dynamics of bimolecular chemical reactions can be examined in liquid
      solutions using infrared absorption spectroscopy with picosecond time resolution.
      On such short time scales, the transient absorption spectra reveal vibrational
      mode and quantum-state-specific energy disposal, followed by vibrational
      relaxation as the energy is dissipated to the surrounding solvent. Comparison
      with energy disposal measurements for gas-phase reactions under single-collision
      conditions offers direct insights into the modification of the energy landscape
      and the nuclear dynamics in the presence of the solvent. The reactions of CN
      radicals with organic molecules in chlorinated solvents exemplify the dynamical
      information that can be obtained. The potential to extend such experiments to a
      range of reactions and solvents is discussed. 

PMID- 26295317
TI  - Surface-Enhanced Raman Spectroelectrochemistry of TTF-Modified Self-Assembled
      Monolayers.
AB  - Surface-enhanced Raman spectroscopy (SERS) was used to monitor the response of a
      self-assembled monolayer (SAM) of a tetrathiafulvalene (TTF) derivative on a gold
      film-over-nanosphere electrode. The electrochemical response observed was
      rationalized in terms of the interactions between TTF moieties as the oxidation
      state was changed. Electrochemical oxidation to form the monocation caused the
      absorbance of the TTF unit to coincide with both the laser excitation wavelength
      and the localized surface plasmon resonance (LSPR), resulting in surface-enhanced
      resonance Raman scattering (SERRS). The vibrational frequency changes that
      accompany electron transfer afford a high-contrast mechanism that can be used to
      determine the oxidation state of the TTF unit in an unambiguous manner. 

PMID- 26295318
TI  - Loading-Controlled Stiffening in Nanoconfined Ionic Liquids.
AB  - An important strategy for using ionic liquids is to immobilize them by
      impregnation of supports or incorporation into porous solids to obtain materials
      called "ionogels". Of considerable importance for applications (electrolyte
      membranes, supported catalysts, etc.), such confinement results in dramatic
      changes in the physicochemical properties of the ionic liquid. Here, we report
      molecular simulations of a silica nanopore that is gradually filled with a
      typical imidazolium salt ionic liquid to obtain a realistic model of these
      ionogels. Despite the significant layering and stiffening of the ionic liquid in
      the vicinity of the silica surface, the pair correlation functions and magnitude
      of its dynamics clearly evidence liquid-like behavior. An increase in the self
      diffusivity and ionic conductivity, associated with a decrease in the
      characteristic residence times of ions at the silica surface, is observed upon
      increasing the loading as the ionic liquid fills the nanopore center and tends to
      recover its bulk properties. 

PMID- 26295319
TI  - Hydroxide Hydrogen Bonding: Probing the Solvation Structure through Ultrafast
      Time Domain Raman Spectroscopy.
AB  - The mechanism of charge transport in aqueous media is critical in molecular,
      materials, and life sciences. The structure of the solvated hydroxide ion has
      been an area of some controversy. Polarization-resolved ultrafast time domain
      polarizability relaxation is used here to resolve the terahertz frequency Raman
      spectrum of hydroxide solutions. The measurements reveal the totally symmetric
      hydrogen-bond stretching (HO(-)...HOH) mode of the solvated hydroxide, permitting
      an experimental measurement of the bond force constant. The observed polarized
      Raman spectra are compared with those obtained from DFT calculations performed on
      HO(-)(H2O)n clusters. Good agreement between the observed frequency and the
      polarization dependence is found for the n = 3 or 4 clusters, particularly for
      those in which the solvating water molecules adopt a planar structure. The
      frequency of the symmetric stretch increases with concentration, consistent with
      an effect of ionic strength on either the H-bond or the structure of the cluster.

PMID- 26295320
TI  - Solvents' Critical Role in Nonaqueous Lithium-Oxygen Battery Electrochemistry.
AB  - Among the many important challenges facing the development of Li-air batteries,
      understanding the electrolyte's role in producing the appropriate reversible
      electrochemistry (i.e., 2Li(+) + O2 + 2e(-) <-> Li2O2) is critical. Quantitative
      differential electrochemical mass spectrometry (DEMS), coupled with isotopic
      labeling of oxygen gas, was used to study Li-O2 electrochemistry in various
      solvents, including carbonates (typical Li ion battery solvents) and
      dimethoxyethane (DME). In conjunction with the gas-phase DEMS analysis,
      electrodeposits formed during discharge on Li-O2 cell cathodes were characterized
      using ex situ analytical techniques, such as X-ray diffraction and Raman
      spectroscopy. Carbonate-based solvents were found to irreversibly decompose upon
      cell discharge. DME-based cells, however, produced mainly lithium peroxide on
      discharge. Upon cell charge, the lithium peroxide both decomposed to evolve
      oxygen and oxidized DME at high potentials. Our results lead to two conclusions;
      (1) coulometry has to be coupled with quantitative gas consumption and evolution
      data to properly characterize the rechargeability of Li-air batteries, and (2)
      chemical and electrochemical electrolyte stability in the presence of lithium
      peroxide and its intermediates is essential to produce a truly reversible Li-O2
      electrochemistry. 

PMID- 26295321
TI  - Theoretical Study of the Surface Complex between TiO2 and TCNQ Showing
      Interfacial Charge-Transfer Transitions.
AB  - The surface complex of TiO2 nanoparticles and TCNQ was studied using density
      functional theory (DFT) calculations. The structure of the surface complex was
      optimized, showing an IR spectrum analogous to the experimental spectrum. From
      time-dependent DFT calculations based on this optimized structure, we
      demonstrated that the interfacial charge-transfer transitions from the HOMO of
      the surface-bound TCNQ molecule to the unoccupied levels of the TiO2 nanocluster
      occur in the visible to near-IR region. 

PMID- 26295322
TI  - Free-Energy Density Functional of Ions at a Dielectric Interface.
AB  - Ions at dielectric interfaces are found in a wide range of applications including
      biology, nanofluidics, and fuel cells. Often, the excluded volume of the ions has
      first-order effects on measured properties. Here, density functional theory of
      fluids is used to develop a statistical mechanical theory of how ions (charged
      hard spheres of different sizes) arrange around a dielectric interface. 

PMID- 26295323
TI  - Sensitivity Enhancement in Solid-State Separated Local Field NMR Experiments by
      the Use of Adiabatic Cross-Polarization.
AB  - Measurement of dipolar couplings using separated local field (SLF) NMR experiment
      is a powerful tool for structural and dynamics studies of oriented molecules such
      as liquid crystals and membrane proteins in aligned lipid bilayers. Enhancing the
      sensitivity of such SLF techniques is of significant importance in present-day
      solid-state NMR methodology. The present study considers the use of adiabatic
      cross-polarization for this purpose, which is applied for the first time to one
      of the well-known SLF techniques, namely, polarization inversion spin exchange at
      the magic angle (PISEMA). The experiments have been carried out on a single
      crystal of a model peptide, and a dramatic enhancement in signal-to-noise up to
      90% has been demonstrated. 

PMID- 26295324
TI  - Ultrafast Coherent Electron-Hole Separation Dynamics in a Fullerene Derivative.
AB  - The use of fullerene derivatives as electron donors in bulk heterojunctions is a
      promising development in the search for efficient energy conversion in hybrid
      solar cells. A long-lived photoexcited electron-hole pair will give rise to
      increased efficiency in photoenergy conversion. One way to prevent fast electron
      hole recombination is to engineer fullerene derivatives that exhibit intrinsic
      electron-hole separation through accessible charge-transfer excited states. In
      this letter, the dynamics of photoexcited electron-hole pairs in a C60 derivative
      is studied using the real-time time-dependent density functional theory. Although
      the charge-transfer excited state is not directly accessible from the ground
      state, intrinsic coherent electron-hole separation is observed following
      photoexcition as a result of direct coupling between excited states. Ultrafast
      charge-transfer dynamics is the dominant phenomenon in <60 fs after visible
      photoexcitation. This work provides insights into the characteristics of
      ultrafast dynamics in photoexcited fullerene derivatives, and aids in the
      rational design of efficient solar cells. 

PMID- 26295325
TI  - Neutral Nanosheets that Gel: Exfoliated Layered Double Hydroxides in Toluene.
AB  - A simple strategy to exfoliate inorganic layered double hydroxide (LDH) solids to
      their ultimate constituent, intact single layers of nanometer thickness and
      micrometer size, is presented. The procedure involves intercalation of an ionic
      surfactant that forms a hydrophobic anchored surfactant bilayer in the galleries
      of the solid followed by simply stirring the intercalated solid in toluene. The
      method is rapid but at the same time gentle enough to produce exfoliated
      nanosheets of regular morphology that are electrically neutral and form stable
      gels at higher concentrations. In this Letter, we describe the phenomena and use
      molecular dynamics simulations to show that exfoliation of the LDH in toluene is
      a consequence of the modification of the cohesive dispersive interactions between
      surfactant chains anchored on opposing inorganic sheets by the toluene molecules.
      The toluene molecules function as a molecular glue, holding the surfactant
      anchored LDH sheets together, leading to gel formation. 

PMID- 26295326
TI  - Surface-Enhanced Femtosecond Stimulated Raman Spectroscopy.
AB  - Surface-enhanced Raman spectroscopy (SERS) and femtosecond stimulated Raman
      spectroscopy (FSRS) have revolutionized the Raman spectroscopy field. SERS
      provides spectroscopic detection of single molecules, and FSRS enables the
      acquisition of Raman spectra on the ultrafast time scale of molecular motion.
      Here, we present the first successful combination of these two techniques,
      demonstrating surface-enhanced femtosecond stimulated Raman spectroscopy (SE
      FSRS) using gold nanoantennas with embedded reporter molecules. Using a
      picosecond Raman and femtosecond probe pulse, the time- and ensemble-averaged
      enhancement factor is estimated to be in the range of 10(4)-10(6). We report the
      line shapes, power dependence, and magnitude of the SE-FSRS signal and discuss
      contributions to sample degradation on the minute time scale. With these first
      successful proof-of-principle experiments, time-resolved SE-FSRS techniques can
      now be rationally attempted with the goals of investigating the dynamics of
      plasmonic materials as well as examining the contributions of environmental
      heterogeneities by probing more homogeneous molecular subsets. 

PMID- 26295327
TI  - Photodetachment of Isolated Bicarbonate Anion: Electron Binding Energy of
      HCO3(.).
AB  - We report the first direct photodetachment photoelectron spectroscopy of HCO3(-)
      in the gas phase under low-temperature conditions. The observed photoelectron
      spectra are complicated due to excitations of manifolds in both vibrational and
      electronic states. A long and single vibrational progression with a frequency of
      530 +/- 20 cm(-1) is partially resolved in the threshold of the T = 20 K, 266 nm
      spectrum. The adiabatic electron detachment energy (ADE) of HCO3(-), or, in other
      words, the electron affinity (EA) of neutral HCO3, is experimentally determined
      from the (0,0) transition to be 3.680 +/- 0.015 eV. The computed values of the
      Franck-Condon integral and intensity are favorable for observing the (0,0)
      transition. High-level ab initio calculations at the CCSD(T) level of theory
      produce an estimated anharmonic frequency of 546 cm(-1) for HCO3 and a value of
      3.79 eV for the (0,0) transition, both in good agreement with the experimentally
      determined values. 

PMID- 26295328
TI  - Interaction of Gold Clusters with a Hydroxylated Surface.
AB  - We explore the interaction between gold nanoclusters and a fully hydroxylated
      surface, Mg(OH)2's basal plane, by using a density functional theory-enabled
      local basin-hopping technique for global-minimum search. We find strong
      interaction of gold nanoclusters with the surface hydroxyls via a short bond
      between edge Au atoms and O atoms of the -OH groups. We expect that this strong
      interaction is ubiquitous on hydroxylated support surfaces and helps the gold
      nanoclusters against sintering, thereby contributing to their CO-oxidation
      activity at low temperatures. 

PMID- 26295329
TI  - Unveiling Electron Promiscuity.
AB  - Although the wave-like proclivity of electrons for delocalization is familiar to
      every student of chemistry, it seems that electrons may have less respect for
      atomic and molecular boundaries than one might have considered proper. The
      boundaries in question include those between H-bonded dimers and within hydrated
      clusters, as well as those of aqueous cavities, colloidal suspensions, and
      macroscopic air-water and oil-water interfaces. Unveiling the promiscuous
      behavior of electrons at such frontiers may both raise eyebrows and demand
      acknowledgment. 

PMID- 26295330
TI  - Improved Sensitivity of Localized Surface Plasmon Resonance Transducers Using
      Reflection Measurements.
AB  - The refractive index sensitivity (RIS) of a localized surface plasmon resonance
      (LSPR) transducer is one of the key parameters determining its effectiveness in
      sensing applications. LSPR spectra of nanoparticulate gold films, including Au
      island films prepared by evaporation on glass and annealing as well as
      immobilized Au nanoparticle (NP) films, were measured in the transmission and
      reflection modes. It is shown that the RIS, measured as the wavelength shift in
      solvents with varying refractive index (RI), is significantly higher in
      reflection measurements. 

PMID- 26295331
TI  - Solvent Effects on Reactions and Electrons.

PMID- 26295332
TI  - Heat Shock Protein 90 Inhibition in Cancer Drug Discovery: From Chemistry to
      Futural Clinical Applications.
AB  - Heat shock protein 90 (Hsp90) is an important member of the chaperone protein
      family and it is involved in stabilization, regulation, and maintenance of
      oncogenic client proteins with co-chaperones. Cochaperones regulate the ATPase
      activity of Hsp90 and its interactions with oncogenic client proteins. Therefore,
      Hsp90 and its co-chaperones have become significant therapeutic targets for
      cancer treatment. Many chemical compounds have been evaluated for Hsp90
      inhibition as well as significant results were obtained in clinical trials. In
      this paper, we emphasize on the key roles of Hsp90 and its co-chaperones in
      tumorigenesis and overview therapeutic strategies of Hsp90 inhibition in
      oncology. 

PMID- 26295333
TI  - Exploring a Novel Target Treatment on Breast Cancer: Aloe-emodin Mediated
      Photodynamic Therapy Induced Cell Apoptosis and Inhibited Cell Metastasis.
AB  - Photodynamic therapy (PDT) as a clinical cancer therapy, is a mild therapy, which
      involves application of photosensitizers (PSs) located in target cells and then
      irradiated by corresponding wavelength. The activation of PSs generates radical
      oxygen species (ROS) to exert a selective cytotoxic activity for the target
      cells. Aloe-emodin (AE) has been found to be an anti-tumor agent in many studies,
      and has also been demonstrated as a photosensitizer, in the recent years. In
      order to study the mechanisms of aloe-emodin as a photosensitizer, we
      investigated the mechanisms of photo-cytotoxicity induced by aloe-emodin in
      breast cancer MCF-7 cells in the present study. Analysis of cell proliferation
      evidenced that there was a drastic depression after photodynamic treatment with a
      series of aloe-emodin concentrations and light doses. We observed changes in
      apoptosis and demonstrated that the mechanisms of apoptosis were involved in
      mitochondrial and endoplasmic reticulum death pathways. The capacity of adhesion,
      migration and invasion of breast cells was measured using WST8 and transwell
      assay and demonstrated that AE-PDT significantly inhibited adhesion, migration
      and invasion of MCF-7cells. The expression of MMP2, MMP9, VEGF and Nrf2
      demonstrated that the metastasis was related to oxidative stress. Analysis of
      changes in cytoskeleton components (F-actin) evidenced cytoskeleton
      disorganization after treatment with AE-PDT. Taken together, the present results
      indicated that PDT with aloe-emodin effectively suppressed cancer development in
      MCF-7cells, suggesting the potential of AE as a new photosensitizer in PDT which
      can provide a new modility for treating cancer.

PMID- 26295334
TI  - Ultraselective homogeneous electrochemical biosensor for DNA species related to
      oral cancer based on nicking endonuclease assisted target recycling
      amplification.
AB  - Traditional electrochemical DNA biosensors need DNA immobilization on the
      electrode surface, which is tedious and time-consuming. In this study, a simple
      but ultraselective electrochemical DNA biosensor had been designed to determine
      target DNA species related to oral cancer overexpressed 1 in saliva, which
      combines the signal amplification of nicking endonuclease assisted target
      recycling with the immobilization-free electrochemical method. The complementary
      substrate strand of target DNA species contains a simple asymmetric sequence had
      been modified with a methylene blue at the 3' terminal first, which cannot
      diffuse easily to the negative charged ITO electrode surface due to the abundant
      negative charges. The presence of the target DNA would trigger the formation of
      double-stranded DNA (dsDNA). Then the nicking endonuclease can recognize the
      simple asymmetric sequence in the dsDNA and cleave the substrate strand of ds-DNA
      into two pieces, a long ssDNA and a 2-base ssDNA linked with methylene blue. The
      short one can diffuse easily to the negative charged ITO electrode surface and
      results in the enhanced electrochemical response detected. At the same time, the
      target DNA can dissociate from the dsDNA and trigger the next round of
      hybridization, cleavage, and releasing, which results in the signal
      amplification. This homogeneous DNA biosensor can detect as low as 0.35 pM (S/N =
      3) target DNA. Compared with the traditional heterogeneous electrochemical DNA
      biosensors, which are tedious and time-consuming due to the complex DNA
      immobilization process, the assay not only owns the merits of simple and high
      efficiency since performed in a homogeneous solution but also exhibits a high
      distinction ability to single-base mismatch, double-bases mismatch, and
      noncomplementary DNA sequence. 

PMID- 26295335
TI  - Bond Energies and Thermochemical Properties of Ring-Opened Diradicals and
      Carbenes of exo-Tricyclo[5.2.1.0(2,6)]decane.
AB  - Exo-tricyclo[5.2.1.0(2,6)]decane (TCD) or exo-tetrahydrodicyclopentadiene is an
      interesting strained ring compound and the single-component high-energy density
      hydrocarbon fuel known as JP-10. Important initial reactions of TCD at high
      temperatures could cleave a strained carbon-carbon (C-C) bond in the ring system
      creating diradicals also constrained by the remaining ring system. This study
      determines the thermochemical properties of these diradicals (TCD-H2 mJ-nJ where
      m and n correspond to the cleaved carbons sites) including the carbon-carbon bond
      dissociation energy (C-C BDE) corresponding to the cleaved TCD site.
      Thermochemical properties including enthalpies (DeltaH degrees f298), entropies
      (S(T)), heat capacities (Cp(T)), and C-H and C-C BDEs for the parent (TCD-H2 m
      n), radical (TCD-H2 mJ-n and m-nJ), diradical (TCD-H2 mJ-nJ), and carbene (TCD-H2
      mJJ-n and m-nJJ) species are determined. Structures, vibrational frequencies,
      moments of inertia, and internal rotor potentials are calculated at the B3LYP/6
      31G(d,p) level of theory. Standard enthalpies of formation in the gas phase for
      the TCD-H2 m-n parent and radical species are determined using the B3LYP density
      functional theory and the higher level G3MP2B3 and CBS-QB3 composite methods. For
      singlet and triplet TCD diradicals and carbenes, M06-2X, omegaB97X-D, and CCSD(T)
      methods are included in the analysis to determine DeltaH degrees f298 values. The
      C-C BDEs are further calculated using CASMP2(2,2)/aug-cc-pvtz//CASSCF(2,2)/cc
      pvtz and with the CASMP2 energies extrapolated to the complete basis set limit.
      The bond energies calculated with these methods are shown to be comparable to the
      other calculation methods. Isodesmic work reactions are used for enthalpy
      analysis of these compounds for effective cancelation of systematic errors
      arising from ring strain. C-C BDEs range from 77.4 to 84.6 kcal mol(-1) for TCD
      diradical singlet species. C-H BDEs for the parent TCD-H2 m-n carbon sites range
      from 93 to 101 kcal mol(-1) with a similar range seen for loss of the second
      hydrogen to generate the diradical singlet species. A wider range for C-C BDEs is
      seen for the carbenes from about 77 to 100 kcal mol(-1) as compared to the
      diradicals. Results from the DFT methods for the parents, radicals, diradicals,
      and carbenes are in good agreement with results from the composite methods using
      our sets of work reactions. 

PMID- 26295336
TI  - The Impact of Accelerated Right Prefrontal High-Frequency Repetitive Transcranial
      Magnetic Stimulation (rTMS) on Cue-Reactivity: An fMRI Study on Craving in
      Recently Detoxified Alcohol-Dependent Patients.
AB  - In alcohol-dependent patients craving is a difficult-to-treat phenomenon. It has
      been suggested that high-frequency (HF) repetitive transcranial magnetic
      stimulation (rTMS) may have beneficial effects. However, exactly how this
      application exerts its effect on the underlying craving neurocircuit is currently
      unclear. In an effort to induce alcohol craving and to maximize detection of HF
      rTMS effects to cue-induced alcohol craving, patients were exposed to a block and
      event-related alcohol cue-reactivity paradigm while being scanned with fMRI.
      Hence, we assessed the effect of right dorsolateral prefrontal cortex (DLPFC)
      stimulation on cue-induced and general alcohol craving, and the related craving
      neurocircuit. Twenty-six recently detoxified alcohol-dependent patients were
      included. First, we evaluated the impact of one sham-controlled stimulation
      session. Second, we examined the effect of accelerated right DLPFC HF-rTMS
      treatment: here patients received 15 sessions in an open label accelerated
      design, spread over 4 consecutive days. General craving significantly decreased
      after 15 active HF-rTMS sessions. However, cue-induced alcohol craving was not
      altered. Our brain imaging results did not show that the cue-exposure affected
      the underlying craving neurocircuit after both one and fifteen active HF-rTMS
      sessions. Yet, brain activation changes after one and 15 HF-rTMS sessions,
      respectively, were observed in regions associated with the extended reward system
      and the default mode network, but only during the presentation of the event
      related paradigm. Our findings indicate that accelerated HF-rTMS applied to the
      right DLPFC does not manifestly affect the craving neurocircuit during an alcohol
      related cue-exposure, but instead it may influence the attentional network. 

PMID- 26295337
TI  - Development and Validation of a Next-Generation Sequencing Assay for BRCA1 and
      BRCA2 Variants for the Clinical Laboratory.
AB  - The objective of this study was to design and validate a next-generation
      sequencing assay (NGS) to detect BRCA1 and BRCA2 mutations. We developed an assay
      using random shearing of genomic DNA followed by RNA bait tile hybridization and
      NGS sequencing on both the Illumina MiSeq and Ion Personal Gene Machine (PGM). We
      determined that the MiSeq Reporter software supplied with the instrument could
      not detect deletions greater than 9 base pairs. Therefore, we developed an
      alternative alignment and variant calling software, Quest Sequencing Analysis
      Pipeline (QSAP), that was capable of detecting large deletions and insertions. In
      validation studies, we used DNA from 27 stem cell lines, all with known
      deleterious BRCA1 or BRCA2 mutations, and DNA from 67 consented control
      individuals who had a total of 352 benign variants. Both the MiSeq/QSAP
      combination and PGM/Torrent Suite combination had 100% sensitivity for the 379
      known variants in the validation series. However, the PGM/Torrent Suite
      combination had a lower intra- and inter-assay precision of 96.2% and 96.7%,
      respectively when compared to the MiSeq/QSAP combination of 100% and 99.4%,
      respectively. All PGM/Torrent Suite inconsistencies were false-positive variant
      assignments. We began commercial testing using both platforms and in the first
      521 clinical samples MiSeq/QSAP had 100% sensitivity for BRCA1/2 variants,
      including a 64-bp deletion and a 10-bp insertion not identified by PGM/Torrent
      Suite, which also suffered from a high false-positive rate. Neither the MiSeq nor
      PGM platform with their supplied alignment and variant calling software are
      appropriate for a clinical laboratory BRCA sequencing test. We have developed an
      NGS BRCA1/2 sequencing assay, MiSeq/QSAP, with 100% analytic sensitivity and
      specificity in the validation set consisting of 379 variants. The MiSeq/QSAP
      combination has sufficient performance for use in a clinical laboratory. 

PMID- 26295338
TI  - Appraisals Generate Specific Configurations of Facial Muscle Movements in a
      Gambling Task: Evidence for the Component Process Model of Emotion.
AB  - Scherer's Component Process Model provides a theoretical framework for research
      on the production mechanism of emotion and facial emotional expression. The model
      predicts that appraisal results drive facial expressions, which unfold
      sequentially and cumulatively over time. In two experiments, we examined facial
      muscle activity changes (via facial electromyography recordings over the
      corrugator, cheek, and frontalis regions) in response to events in a gambling
      task. These events were experimentally manipulated feedback stimuli which
      presented simultaneous information directly affecting goal conduciveness
      (gambling outcome: win, loss, or break-even) and power appraisals (Experiment 1
      and 2), as well as control appraisal (Experiment 2). We repeatedly found main
      effects of goal conduciveness (starting ~600 ms), and power appraisals (starting
      ~800 ms after feedback onset). Control appraisal main effects were inconclusive.
      Interaction effects of goal conduciveness and power appraisals were obtained in
      both experiments (Experiment 1: over the corrugator and cheek regions; Experiment
      2: over the frontalis region) suggesting amplified goal conduciveness effects
      when power was high in contrast to invariant goal conduciveness effects when
      power was low. Also an interaction of goal conduciveness and control appraisals
      was found over the cheek region, showing differential goal conduciveness effects
      when control was high and invariant effects when control was low. These
      interaction effects suggest that the appraisal of having sufficient control or
      power affects facial responses towards gambling outcomes. The result pattern
      suggests that corrugator and frontalis regions are primarily related to cognitive
      operations that process motivational pertinence, whereas the cheek region would
      be more influenced by coping implications. Our results provide first evidence
      demonstrating that cognitive-evaluative mechanisms related to goal conduciveness,
      control, and power appraisals affect facial expressions dynamically over time,
      immediately after an event is perceived. In addition, our results provide further
      indications for the chronography of appraisal-driven facial movements and the
      underlying cognitive processes. 

PMID- 26295341
TI  - Resiliency of EEG-Based Brain Functional Networks.
AB  - Applying tools available in network science and graph theory to study brain
      networks has opened a new era in understanding brain mechanisms. Brain functional
      networks extracted from EEG time series have been frequently studied in health
      and diseases. In this manuscript, we studied failure resiliency of EEG-based
      brain functional networks. The network structures were extracted by analysing EEG
      time series obtained from 30 healthy subjects in resting state eyes-closed
      conditions. As the network structure was extracted, we measured a number of
      metrics related to their resiliency. In general, the brain networks showed worse
      resilient behaviour as compared to corresponding random networks with the same
      degree sequences. Brain networks had higher vulnerability than the random ones (P
      < 0.05), indicating that their global efficiency (i.e., communicability between
      the regions) is more affected by removing the important nodes. Furthermore, the
      breakdown happened as a result of cascaded failures in brain networks was severer
      (i.e., less nodes survived) as compared to randomized versions (P < 0.05). These
      results suggest that real EEG-based networks have not been evolved to possess
      optimal resiliency against failures. 

PMID- 26295342
TI  - Pervasive Mitochondrial Sequence Heteroplasmy in Natural Populations of Wild
      Carrot, Daucus carota spp. carota L.
AB  - Exceptions to the generally accepted rules that plant mitochondrial genomes are
      strictly maternally inherited and that within-individual sequence diversity in
      those genomes, i.e., heteroplasmy, should be minimal are becoming increasingly
      apparent especially with regard to sequence-level heteroplasmy. These findings
      raise questions about the potential significance of such heteroplasmy for plant
      mitochondrial genome evolution. Still studies quantifying the amount and
      consequences of sequence heteroplasmy in natural populations are rare. In this
      study, we report pervasive sequence heteroplasmy in natural populations of wild
      carrot, a close relative of the cultivated crop. In order to assay directly for
      this heteroplasmy, we implemented a quantitative PCR assay that can detect and
      quantify intra-individual SNP variation in two mitochondrial genes (Cox1 and
      Atp9). We found heteroplasmy in > 60% of all wild carrot populations surveyed and
      in > 30% of the 140 component individuals that were genotyped. Heteroplasmy
      ranged from a very small proportion of the total genotype (e.g., 0.995:0.005) to
      near even mixtures (e.g., 0.590:0.410) in some individuals. These results have
      important implications for the role of intra-genomic recombination in the
      generation of plant mitochondrial genome genotypic novelty. The consequences of
      such recombination are evident in the results of this study through analysis of
      the degree of linkage disequilibrium (LD) between the SNP sites at the two genes
      studied. 

PMID- 26295343
TI  - Correction: Antibacterial and Antifungal Activity of ZnO Containing Glasses.

PMID- 26295339
TI  - FBG1 Is the Final Arbitrator of A1AT-Z Degradation.
AB  - Alpha-1 antitrypsin deficiency is the leading cause of childhood liver failure
      and one of the most common lethal genetic diseases. The disease-causing mutant
      A1AT-Z fails to fold correctly and accumulates in the endoplasmic reticulum (ER)
      of the liver, resulting in hepatic fibrosis and hepatocellular carcinoma in a
      subset of patients. Furthermore, A1AT-Z sequestration in hepatocytes leads to a
      reduction in A1AT secretion into the serum, causing panacinar emphysema in
      adults. The purpose of this work was to elucidate the details by which A1AT-Z is
      degraded in hepatic cell lines. We identified the ubiquitin ligase FBG1, which
      has been previously shown to degrade proteins by both the ubiquitin proteasome
      pathway and autophagy, as being key to A1AT-Z degradation. Using chemical and
      genetic approaches we show that FBG1 degrades A1AT-Z through both the ubiquitin
      proteasome system and autophagy. Overexpression of FBG1 decreases the half-life
      of A1AT-Z and knocking down FBG1 in a hepatic cell line, and in mice results in
      an increase in ATAT. Finally, we show that FBG1 degrades A1AT-Z through a Beclin1
      dependent arm of autophagy. In our model, FBG1 acts as a safety ubiquitin ligase,
      whose function is to re-ubiquitinate ER proteins that have previously undergone
      de-ubiquitination to ensure they are degraded. 

PMID- 26295340
TI  - Over-Expression of Cysteine Leucine Rich Protein Is Related to SAG Resistance in
      Clinical Isolates of Leishmania donovani.
AB  - BACKGROUND: Resistance emergence against antileishmanial drugs, particularly
      Sodium Antimony Gluconate (SAG) has severely hampered the therapeutic strategy
      against visceral leishmaniasis, the mechanism of resistance being
      indistinguishable. Cysteine leucine rich protein (CLrP), was recognized as one of
      the overexpressed proteins in resistant isolates, as observed in differential
      proteomics between sensitive and resistant isolates of L. donovani. The present
      study deals with the characterization of CLrP and for its possible connection
      with SAG resistance. METHODOLOGY AND PRINCIPAL FINDINGS: In pursuance of
      deciphering the role of CLrP in SAG resistance, gene was cloned, over-expressed
      in E. coli system and thereafter antibody was raised. The expression profile of
      CLrP and was found to be over-expressed in SAG resistant clinical isolates of L.
      donovani as compared to SAG sensitive ones when investigated by real-time PCR and
      western blotting. CLrP has been characterized through bioinformatics,
      immunoblotting and immunolocalization analysis, which reveals its post
      translational modification along with its dual existence in the nucleus as well
      as in the membrane of the parasite. Further investigation using a ChIP assay
      confirmed its DNA binding potential. Over-expression of CLrP in sensitive isolate
      of L. donovani significantly decreased its responsiveness to SAG (SbV and SbIII)
      and a shift towards the resistant mode was observed. Further, a significant
      increase in its infectivity in murine macrophages has been observed.
      CONCLUSION/SIGNIFICANCE: The study reports the differential expression of CLrP in
      SAG sensitive and resistant isolates of L. donovani. Functional intricacy of CLrP
      increases with dual localization, glycosylation and DNA binding potential of the
      protein. Further over-expressing CLrP in sensitive isolate of L. donovani shows
      significantly decreased sensitivity towards SAG and increased infectivity as
      well, thus assisting the parasite in securing a safe niche. Results indicates the
      possible contribution of CLrP to antimonial resistance in L. donovani by
      assisting the parasite growth in the macrophages.

PMID- 26295344
TI  - Adaptation and Evaluation of a Multi-Criteria Decision Analysis Model for Lyme
      Disease Prevention.
AB  - Designing preventive programs relevant to vector-borne diseases such as Lyme
      disease (LD) can be complex given the need to include multiple issues and
      perspectives into prioritizing public health actions. A multi-criteria decision
      aid (MCDA) model was previously used to rank interventions for LD prevention in
      Quebec, Canada, where the disease is emerging. The aim of the current study was
      to adapt and evaluate the decision model constructed in Quebec under a different
      epidemiological context, in Switzerland, where LD has been endemic for the last
      thirty years. The model adaptation was undertaken with a group of Swiss
      stakeholders using a participatory approach. The PROMETHEE method was used for
      multi-criteria analysis. Key elements and results of the MCDA model are described
      and contrasted with the Quebec model. All criteria and most interventions of the
      MCDA model developed for LD prevention in Quebec were directly transferable to
      the Swiss context. Four new decision criteria were added, and the list of
      proposed interventions was modified. Based on the overall group ranking,
      interventions targeting human populations were prioritized in the Swiss model,
      with the top ranked action being the implementation of a large communication
      campaign. The addition of criteria did not significantly alter the intervention
      rankings, but increased the capacity of the model to discriminate between highest
      and lowest ranked interventions. The current study suggests that beyond the
      specificity of the MCDA models developed for Quebec and Switzerland, their
      general structure captures the fundamental and common issues that characterize
      the complexity of vector-borne disease prevention. These results should encourage
      public health organizations to adapt, use and share MCDA models as an effective
      and functional approach to enable the integration of multiple perspectives and
      considerations in the prevention and control of complex public health issues such
      as Lyme disease or other vector-borne and zoonotic diseases. 

PMID- 26295345
TI  - Plant Functional Diversity Can Be Independent of Species Diversity: Observations
      Based on the Impact of 4-Yrs of Nitrogen and Phosphorus Additions in an Alpine
      Meadow.
AB  - Past studies have widely documented the decrease in species diversity in response
      to addition of nutrients, however functional diversity is often independent from
      species diversity. In this study, we conducted a field experiment to examine the
      effect of nitrogen and phosphorus fertilization ((NH4)2 HPO4) at 0, 15, 30 and 60
      g m-2 yr-1 (F0, F15, F30 and F60) after 4 years of continuous fertilization on
      functional diversity and species diversity, and its relationship with
      productivity in an alpine meadow community on the Tibetan Plateau. To this
      purpose, three community-weighted mean trait values (specific leaf area, SLA;
      mature plant height, MPH; and seed size, SS) for 30 common species in each
      fertilization level were determined; three components of functional diversity
      (functional richness, FRic; functional evenness, FEve; and Rao's index of
      quadratic entropy, FRao) were quantified. Our results showed that: (i) species
      diversity sharply decreased, but functional diversity remained stable with
      fertilization; (ii) community-weighted mean traits (SLA and MPH) had a
      significant increase along the fertilization level; (iii) aboveground biomass was
      not correlated with functional diversity, but it was significantly correlated
      with species diversity and MPH. Our results suggest that decreases in species
      diversity due to fertilization do not result in corresponding changes in
      functional diversity. Functional identity of species may be more important than
      functional diversity in influencing aboveground productivity in this alpine
      meadow community, and our results also support the mass ratio hypothesis; that
      is, the traits of the dominant species influenced the community biomass
      production. 

PMID- 26295346
TI  - Tipping the Scale from Disorder to Alpha-helix: Folding of Amphiphilic Peptides
      in the Presence of Macroscopic and Molecular Interfaces.
AB  - Secondary amphiphilicity is inherent to the secondary structural elements of
      proteins. By forming energetically favorable contacts with each other these
      amphiphilic building blocks give rise to the formation of a tertiary structure.
      Small proteins and peptides, on the other hand, are usually too short to form
      multiple structural elements and cannot stabilize them internally. Therefore,
      these molecules are often found to be structurally ambiguous up to the point of a
      large degree of intrinsic disorder in solution. Consequently, their
      conformational preference is particularly susceptible to environmental conditions
      such as pH, salts, or presence of interfaces. In this study we use molecular
      dynamics simulations to analyze the conformational behavior of two synthetic
      peptides, LKKLLKLLKKLLKL (LK) and EAALAEALAEALAE (EALA), with built-in secondary
      amphiphilicity upon forming an alpha-helix. We use these model peptides to
      systematically study their aggregation and the influence of macroscopic and
      molecular interfaces on their conformational preferences. We show that the
      peptides are neither random coils in bulk water nor fully formed alpha helices,
      but adopt multiple conformations and secondary structure elements with short
      lifetimes. These provide a basis for conformation-selection and population-shift
      upon environmental changes. Differences in these peptides' response to
      macroscopic and molecular interfaces (presented by an aggregation partner) can be
      linked to their inherent alpha-helical tendencies in bulk water. We find that the
      peptides' aggregation behavior is also strongly affected by presence or absence
      of an interface, and rather subtly depends on their surface charge and
      hydrophobicity. 

PMID- 26295348
TI  - Correction: Chronic Lung Injury by Constitutive Expression of Activation-Induced
      Cytidine Deaminase Leads to Focal Mucous Cell Metaplasia and Cancer.

PMID- 26295347
TI  - Livestock First Reached Southern Africa in Two Separate Events.
AB  - After several decades of research on the subject, we now know when the first
      livestock reached southern Africa but the question of how they got there remains
      a contentious topic. Debate centres on whether they were brought with a large
      migration of Khoe-speakers who originated from East Africa; or whether the
      livestock were traded down-the-line among hunter-gatherer communities; or indeed
      whether there was a long history of diverse small scale population movements in
      this part of the world, one or more of which 'infiltrated' livestock into
      southern Africa. A new analysis of the distribution of stone toolkits from a
      sizeable sample of sub-equatorial African Later Stone Age sites, coupled with
      existing knowledge of the distribution of the earliest livestock remains and
      ceramics vessels, has allowed us to isolate two separate infiltration events that
      brought the first livestock into southern Africa just over 2000 years ago; one
      infiltration was along the Atlantic seaboard and another entered the middle
      reaches of the Limpopo River Basin. These findings agree well with the latest
      results of genetic research which together indicate that multiple, small-scale
      infiltrations probably were responsible for bringing the first livestock into
      southern Africa. 

PMID- 26295349
TI  - Genetic Identification Is Critical for the Diagnosis of Parkinsonism: A Chinese
      Pedigree with Early Onset of Parkinsonism.
AB  - BACKGROUND: A number of hereditary neurological diseases display
      indistinguishable features at the early disease stage. Parkinsonian symptoms can
      be found in numerous diseases, making it difficult to get a definitive early
      diagnosis of primary causes for patients with onset of parkinsonism. The accurate
      and early diagnosis of the causes of parkinsonian patients is important for
      effective treatments of these patients. METHODS: We have identified a Chinese
      family (82 family members over four generations with 21 affected individuals)
      that manifested the characterized symptoms of parkinsonism and was initially
      diagnosed as Parkinson's disease. We followed up with the family for two years,
      during which we carried out clinical observations, Positron Emission Tomography
      Computed Tomography neuroimaging analysis, and exome sequencing to correctly
      diagnose the case. RESULTS: During the two-year follow-up period, we performed
      comprehensive medical history collection, physical examination, and structural
      and functional neuroimaging studies of this Chinese family. We found that the
      patient exhibited progressive deteriorated parkinsonism with Parkinson disease
      like neuropathology and also had a good response to the initial levodopa
      treatment. However, exome sequencing identified a missense mutation, N279K, in
      exon 10 of MAPT gene, verifying that the early parkinsonian symptoms in this
      family are caused by the genetic mutation for hereditary frontotemporal lobar
      dementia. CONCLUSIONS: For the inherited parkinsonian patients who even show the
      neuropathology similar to that in Parkinson's disease and have initial response
      to levodopa treatment, genetic identification of the molecular basis for the
      disease is still required for defining the early diagnosis and correct treatment.

PMID- 26295350
TI  - Responses to Success: Seeking Pleasant Experiences before a Task Is Complete?
AB  - Although engaging in pleasant experiences following successful performance may be
      hedonically rewarding, in the present research we proposed that individuals might
      forego pleasant experiences when they have not yet completed a task. In Study 1
      (N = 100), participants reported the extent to which they would like to engage in
      pleasant experiences in a hypothetical situation where their performance outcome
      on a task (successful vs. average) and task completion (task in progress vs.
      completed) were manipulated. In Study 2 (N = 115), participants were in a real
      situation in which they achieved either a successful or average performance
      outcome. Task completion was manipulated (task in progress vs. completed) and
      motivation to engage in a pleasant experience was assessed by a behavioral
      measure. Results of both studies provided support for our prediction by showing
      individuals to have a lower desire to engage in pleasant experiences following
      successful, but not average, performance when the task was in progress than when
      it was complete. These findings are discussed in light of the underlying
      mechanisms and consequences of the tendency to forego pleasant experiences. 

PMID- 26295352
TI  - Interplay of Octahedral Rotations and Lone Pair Ferroelectricity in CsPbF3.
AB  - CsPbF3 is the only experimentally synthesized ABF3 fluoride perovskite with a
      polar ground state. We use CsPbF3 as a guide in our search for rules to
      rationally design new ABX3 polar fluorides and halides from first-principles and
      as a model compound to study the interactions of lone pairs, octahedral
      rotations, and A- and B-site driven ferroelectricity. We find that the lone pair
      cation on the B-site serves to stabilize a polar ground state, analogous to the
      role of lone pair cations on the A-site of oxide perovskites. However, we also
      find that the lone pair determines the pattern of nonpolar structural
      distortions, rotations of the PbF6 octahedra, that characterize the lowest energy
      structure. This result is remarkable since rotations are typically associated
      with bonding preferences of the A-site cation (here Cs(+)), whereas the Pb(2+)
      cation occupies the B site. We show that the coordination requirements of the A
      site cation and the stereoactivity of the B-site lone pair cation compete or
      cooperate via the anionic displacements that accompany polar distortions. We
      consider the generalizability of our findings for CsPbF3 and how they may be
      extended to the oxide perovskites as well as to the organic-inorganic hybrid
      halide perovskite photovoltaics. 

PMID- 26295351
TI  - Induction of a Torpor-Like State by 5'-AMP Does Not Depend on H2S Production.
AB  - BACKGROUND: Therapeutic hypothermia is used to reduce ischemia/reperfusion injury
      (IRI) during organ transplantation and major surgery, but does not fully prevent
      organ injury. Interestingly, hibernating animals undergo repetitive periods of
      low body temperature called 'torpor' without signs of organ injury. Recently, we
      identified an essential role of hydrogen sulfide (H2S) in entrance into torpor
      and preservation of kidney integrity during hibernation. A torpor-like state can
      be induced pharmacologically by injecting 5'-Adenosine monophosphate (5'-AMP).
      The mechanism by which 5'-AMP leads to the induction of a torpor-like state, and
      the role of H2S herein, remains to be unraveled. Therefore, we investigated
      whether induction of a torpor-like state by 5-AMP depends on H2S production.
      METHODS: To study the role of H2S on the induction of torpor, amino-oxyacetic
      acid (AOAA), a non-specific inhibitor of H2S, was administered before injection
      with 5'-AMP to block endogenous H2S production in Syrian hamster. To assess the
      role of H2S on maintenance of torpor induced by 5'-AMP, additional animals were
      injected with AOAA during torpor. KEY RESULTS: During the torpor-like state
      induced by 5'-AMP, the expression of H2S- synthesizing enzymes in the kidneys and
      plasma levels of H2S were increased. Blockade of these enzymes inhibited the rise
      in the plasma level of H2S, but neither precluded torpor nor induced arousal.
      Remarkably, blockade of endogenous H2S production was associated with increased
      renal injury. CONCLUSIONS: Induction of a torpor-like state by 5'-AMP does not
      depend on H2S, although production of H2S seems to attenuate renal injury.
      Unraveling the mechanisms by which 5'-AMP reduces the metabolism without organ
      injury may allow optimization of current strategies to limit (hypothermic) IRI
      and improve outcome following organ transplantation, major cardiac and brain
      surgery.

PMID- 26295353
TI  - Differential impact of mental health multimorbidity on healthcare costs in
      diabetes.
AB  - OBJECTIVES: This study assessed the prevalence and specific costs associated with
      discrete multimorbid mental health disease clusters in adults with diabetes
      mellitus (DM). STUDY DESIGN: Longitudinal analysis of a retrospective cohort.
      METHODS: We performed a 5-year longitudinal analysis of a retrospective cohort of
      733,071 patients with DM from the US Veterans Health Administration (VHA) between
      2002 and 2006. The mental health comorbidities (MHCs) examined included
      depression, substance abuse, and psychosis. Our primary outcomes of interest were
      total inpatient, outpatient, and pharmacy costs measured in 2012 US$ from the
      perspective of the VHA. RESULTS: DM was present with comorbid depression,
      substance abuse, and psychosis in 12.1%, 3.7%, and 4.2% of patients,
      respectively. Overall, 13.5% of patients had 1 MHC, 2.5% had 2 MHCs, and 0.5% had
      all MHCs. Total inpatient ($1,435,651,415), outpatient ($366,137,435), and
      pharmacy ($90,064,725) costs were highest for patients with DM and comorbid
      depression alone. At the per-patient level, DM plus psychosis and substance abuse
      had the highest inpatient costs ($35,518), DM plus all MHCs had the highest
      outpatient costs ($6962), and DM plus depression and psychosis had the highest
      pharmacy costs ($1753). CONCLUSIONS: DM with comorbid depression is the most
      prevalent MHC combination and is associated with the highest total VHA healthcare
      costs. However, other comorbidity clusters are associated with higher mean per
      patient costs, and may therefore benefit from more intensive intervention.
      Analysis of healthcare expenditures by multimorbid disease clusters can be a
      useful tool for healthcare policy planning.

PMID- 26295354
TI  - Medicare Shared Savings Program: public reporting and shared savings
      distributions.
AB  - OBJECTIVES: To determine if Medicare Shared Savings Program (MSSP) accountable
      care organizations (ACOs) are meeting public reporting requirements related to
      shared savings plans, to quantitate the composition of shared savings
      distribution plans, and to investigate whether early ACO success is associated
      with specific plan or ACO characteristics. STUDY DESIGN: Cross-sectional study.
      METHODS: ACO descriptive characteristics and distribution plan details were
      abstracted from official ACO websites for all 338 active MSSP ACOs launched
      through January 2014. Publicly available MSSP results from 2012 and 2013 start
      date ACOs were used to investigate associations with successful shared savings
      generation. RESULTS: Of current MSSP ACOs, 313 of 338 (93%) maintain a website,
      284 of 338 (84%) provided at least a general statement about shared savings
      distributions, and 176 of 338 (52%) reported detailed allocation percentages to
      ACO participants. On average, ACOs reporting detailed allocations planned to give
      63% (range = 0%-100%; SD = 26.3) to their primary care providers (PCPs),
      specialists, and/or hospitals, and 33% (range = 0%-100%; SD = 25.6) to
      infrastructure. ACOs including a hospital planned to give a larger average
      percentage to participating entities than those without (69% vs 58%; P = .01).
      ACOs planning to give > 50% to their PCPs and specialists were more likely to
      have generated savings (P = .001), as were ACOs composed of > 10 participating
      entities (P = .004). CONCLUSIONS: Just over one-half of MSSP ACOs report detailed
      shared savings distribution plans online, and these plans vary widely. There
      appears to be no single shared savings distribution plan determinate of ACO
      success. Continued investigation of predictors for generating savings is needed
      to inform future shared savings models.

PMID- 26295356
TI  - Opportunity costs of ambulatory medical care in the United States.
AB  - OBJECTIVES: The typical focus in discussions of healthcare spending is on direct
      medical costs such as physician reimbursement. The indirect costs of healthcare
      patient opportunity costs associated with seeking care, for example-have not been
      adequately quantified. We aimed to quantify the opportunity costs for adults
      seeking medical care for themselves or others. STUDY DESIGN: Secondary analysis
      of the 2003-2010 American Time Use Survey (ATUS). METHODS: We used the nationally
      representative 2003-2010 ATUS to estimate opportunity costs associated with
      ambulatory medical visits. We estimated opportunity costs for employed adults
      using self-reported hourly wages and for unemployed adults using a Heckman
      selection model. We used the Medical Expenditure Panel Survey to compare
      opportunity costs with direct costs (ie, patient out-of-pocket, provider
      reimbursement) in 2010. RESULTS: Average total time per visit was 121 minutes
      (95% CI, 118-124), with 37 minutes (95% CI, 36-39) of travel time and 84 minutes
      (95% CI, 81-86) of clinic time. The average opportunity cost per visit was $43,
      which exceeds the average patient's out-of-pocket payment. Total opportunity
      costs per year for all physician visits in the United States were $52 billion in
      2010. For every dollar spent in visit reimbursement, an additional 15 cents were
      spent in opportunity costs. CONCLUSIONS: In the United States, opportunity costs
      associated with ambulatory medical care are substantial. Accounting for patient
      opportunity costs is important for examining US healthcare system efficiency and
      for evaluating methods to improve the efficient delivery of patient-centered
      care.

PMID- 26295355
TI  - A comparison of relative resource use and quality in Medicare Advantage health
      plans versus traditional Medicare.
AB  - OBJECTIVES: Prior analyses of Medicare health plans have examined either
      utilization of services or quality of care, but not both jointly. Our objective
      was to compare utilization and quality for Medicare Advantage (MA) enrollees with
      diabetes or cardiovascular disease to that for similarly defined traditional
      Medicare (TM) beneficiaries. STUDY DESIGN: Cross-sectional matched observational
      study using data for 2007. METHODS: We obtained individual-level Healthcare
      Effectiveness Data and Information Set (HEDIS) relative resource use (RRU) and
      quality data for patients enrolled in MA, and then developed comparable claims
      based measures for matched samples of TM beneficiaries. MAIN OUTCOME MEASURES:
      utilization levels for inpatient care, evaluation and management services, and
      surgery; number of emergency department (ED) and inpatient visits; and quality of
      ambulatory care measures. RESULTS: We studied approximately 680,000 MA health
      maintenance organization (HMO) enrollees with diabetes and 270,000 HMO enrollees
      with cardiovascular conditions. For both conditions and almost all major strata,
      the RRU was lower for those enrolled in MA than for those in TM. Spending for
      those with diabetes was $5223 for MA HMO enrollees compared with $6413 for those
      in TM (cost ratio, 0.81; P < .001). ED utilization rates were consistently lower
      in MA than TM (567 vs 719 visits/1000 enrollees; rate ratio, 0.79; P < .001).
      Health plans that are more established, nonprofit, and/or larger generally had
      lower resource use and better relative quality than did smaller, newer, for
      profit HMOs or preferred provider organizations. CONCLUSIONS: RRU for those with
      diabetes or cardiovascular disease is lower in MA, while quality of care is
      higher. Better MA plans may add value to the care of these major chronic medical
      conditions.

PMID- 26295357
TI  - Clinical efficacy: a cost containment weapon for the 21st century.

PMID- 26295358
TI  - Toxicity of aerosols of nicotine and pyruvic acid (separate and combined) in
      Sprague-Dawley rats in a 28-day OECD 412 inhalation study and assessment of
      systems toxicology.
AB  - Toxicity of nebulized nicotine (Nic) and nicotine/pyruvic acid mixtures (Nic/Pyr)
      was characterized in a 28-day Organization for Economic Co-operation and
      Development 412 inhalation study with additional transcriptomic and lipidomic
      analyses. Sprague-Dawley rats were nose-only exposed, 6 h/day, 5 days/week to
      filtered air, saline, nicotine (50 ug/l), sodium pyruvate (NaPyr, 33.9 ug/l) or
      equimolar Nic/Pyr mixtures (18, 25 and 50 ug nicotine/l). Saline and NaPyr caused
      no health effects, but rats exposed to nicotine-containing aerosols had decreased
      body weight gains and concentration-dependent increases in liver weight. Blood
      neutrophil counts were increased and lymphocyte counts decreased in rats exposed
      to nicotine; activities of alkaline phosphatase and alanine aminotransferase were
      increased, and levels of cholesterol and glucose decreased. The only
      histopathologic finding in non-respiratory tract organs was increased liver
      vacuolation and glycogen content. Respiratory tract findings upon nicotine
      exposure (but also some phosphate-buffered saline aerosol effects) were observed
      only in the larynx and were limited to adaptive changes. Gene expression changes
      in the lung and liver were very weak. Nic and Nic/Pyr caused few significant
      changes (including Cyp1a1 gene upregulation). Changes were predominantly related
      to energy metabolism and fatty acid metabolism but did not indicate an obvious
      toxicity-related response. Nicotine exposure lowered plasma lipids, including
      cholesteryl ester (CE) and free cholesterol and, in the liver, phospholipids and
      sphingolipids. Nic, NaPyr and Nic/Pyr decreased hepatic triacylglycerol and CE.
      In the lung, Nic and Nic/Pyr increased CE levels. These data suggest that only
      minor biologic effects related to inhalation of Nic or Nic/Pyr aerosols were
      observed in this 28-day study. 

PMID- 26295360
TI  - Fertility intentions, power relations and condom use within intimate and other
      non-paying partnerships of women in sex work in Bagalkot District, South India.
AB  - This study aimed to: (1) examine the relationship between interpersonal as well
      as social-demographic, cultural and structural factors, and condom non-use by sex
      workers' main intimate or other non-paying male sex partners (NPPs), as reported
      by a sample of sex workers (SWs); and (2) understand HIV/sexually transmitted
      infections (STIs) risk (e.g., numbers of sexual partners; condom use with
      different partners) among couples comprised of a sub-set of SWs and their NPPs.
      Bivariate and multivariable logistic regression was used to identify factors
      associated with condom non-use at last sex by the main NPP, as reported by SWs.
      Adjusted odds ratios and 95% confidence intervals are reported (AOR[95%CIs]).
      Data were drawn from cross-sectional surveys in Bagalkot District, Karnataka
      State, South India. Responses by SWs whose main NPPs agreed to enrol in the study
      and the main NPP enroled were linked; these responses by couples (pairs of SWs
      and NPPs) were examined to assess sexual risk for HIV/STIs. Overall, this study
      included 257 SWs and 76 NPPs. The data from 67 couples (88.2%) could be linked.
      In over a quarter of partnerships, at least one (SW or NPP) partner reported
      having another type of partner besides each other (and clients of SWs). In
      multivariable analysis, significantly increased odds of condom non-use at last
      sex with the main NPP were found for the following key factors: planning to have
      a child with their main NPP (AOR = 3.71[1.44-9.58]); and having decisions about
      condom use made by their main NPP (AOR = 9.87[4.03-24.16]) or both equally (AOR =
      3.18[1.39-7.80]) (versus by the SWs herself). Our study highlights the potential
      risk for HIV/STI acquisition and transmission between NPPs and SWs, and between
      NPPs and their non-SWs wives and other sex partners. Study results underscore the
      need for HIV/STI prevention approaches that incorporate informed decision-making
      about childbearing and parenting, and empowerment strategies for SWs in the
      context of their relationships with NPPs. 

PMID- 26295359
TI  - Life course socioeconomic status and DNA methylation in genes related to stress
      reactivity and inflammation: The multi-ethnic study of atherosclerosis.
AB  - Epigenetic changes, such as DNA methylation, have been hypothesized to provide a
      link between the social environment and disease development. The purpose of this
      study was to examine associations between life course measures of socioeconomic
      status (SES) and DNA methylation (DNAm) in 18 genes related to stress reactivity
      and inflammation using a multi-level modeling approach that treats DNAm
      measurements as repeat measures within an individual. DNAm and gene expression
      were assessed in purified monocytes for a random subsample of 1,264 non-Hispanic
      white, African-American, and Hispanic participants aged 55-94 from the Multi
      Ethnic Study of Atherosclerosis (MESA). After correction for multiple testing, we
      found that low childhood SES was associated with DNAm in 3 stress-related genes
      (AVP, FKBP5, OXTR) and 2 inflammation-related genes (CCL1, CD1D), low adult SES
      was associated with DNAm in one stress-related gene (AVP) and 5 inflammation
      related genes (CD1D, F8, KLRG1, NLRP12, TLR3), and social mobility was associated
      with DNAm in 3 stress-related genes (AVP, FKBP5, OXTR) and 7 inflammation-related
      genes (CCL1, CD1D, F8, KLRG1, NLRP12, PYDC1, TLR3). In general, low SES was
      associated with increased DNAm. Expression data was available for 7 genes that
      showed a significant relationship between SES and DNAm. In 5 of these 7 genes
      (CD1D, F8, FKBP5, KLRG1, NLRP12), DNAm was associated with gene expression for at
      least one transcript, providing evidence of the potential functional consequences
      of alterations in DNAm related to SES. The results of this study reflect the
      biological complexity of epigenetic data and underscore the need for multi
      disciplinary approaches to study how DNAm may contribute to the social patterning
      of disease. 

PMID- 26295361
TI  - Nanomaterials for wound healing: scope and advancement.
AB  - Innovative methods for treating impaired and hard-to-heal wounds are needed.
      Novel strategies are needed for faster healing by reducing infection,
      moisturizing the wound, stimulating the healing mechanisms, speeding up the wound
      closure and reducing scar formation. In the past few years, nanotechnology has
      been constantly revolutionizing the treatment and management of wound care, by
      offering novel solutions which include but are not limited to: state-of-the-art
      materials, so called 'smart' biomaterials and theranostic nanoparticles.
      Nanotechnology-based therapy has recently announced itself as a possible next
      generation therapy that is able to advance wound healing to cure chronic wounds.
      In this communication, the recent progress in advanced therapy for cutaneous
      wound healing during last 5 years using a nanotechnology-based approach is
      summarized. 

PMID- 26295362
TI  - Syntheses, structures, and (1)H, (13)C{(1)H} and (119)Sn{(1)H} NMR chemical
      shifts of a family of trimethyltin alkoxide, amide, halide and cyclopentadienyl
      compounds.
AB  - The synthesis and full characterization, including Nuclear Magnetic Resonance
      (NMR) data ((1)H, (13)C{(1)H} and (119)Sn{(1)H}), for a series of Me3SnX (X = O
      2,6-(t)Bu2C6H3 (), (Me3Sn)N(2,6-(i)Pr2C6H3) (), NH-2,4,6-(t)Bu3C6H2 (), N(SiMe3)2
      (), NEt2, C5Me5 (), Cl, Br, I, and SnMe3) compounds in benzene-d6, toluene-d8,
      dichloromethane-d2, chloroform-d1, acetonitrile-d3, and tetrahydrofuran-d8 are
      reported. The X-ray crystal structures of Me3Sn(O-2,6-(t)Bu2C6H3) (), Me3Sn(O-2,6
      (i)Pr2C6H3) (), and (Me3Sn)(NH-2,4,6-(t)Bu3C6H2) () are also presented. These
      compiled data complement existing literature data and ease the characterization
      of these compounds by routine NMR experiments. 

PMID- 26295363
TI  - A survey of neuropsychologists' use of validity tests with children and
      adolescents.
AB  - A web-based survey of validity test use by North American neuropsychologists was
      conducted, with 282 participants meeting inclusion criteria. Respondents
      indicated that they use a median of one stand-alone performance validity test
      (PVT), one embedded PVT, and one symptom validity test (SVT) per pediatric
      assessment. The vast majority of respondents indicated they give at least one PVT
      (92%) and at least one SVT (88%) during each pediatric assessment. A meaningful
      difference in validity use (i.e., at least a medium effect size) was only found
      for those who engage in forensic work, with those clinicians giving more stand
      alone PVTs than those who do not conduct forensic work. The most frequently used
      validity measures in pediatric assessments are presented, as are reasons
      participants reported for both using and not using validity tests. Limitations
      and qualitative comparisons to other surveys on validity test use with adults are
      discussed.

PMID- 26295364
TI  - Mycobacterium abscessus Complex Infections in Humans.
AB  - Mycobacterium abscessus complex comprises a group of rapidly growing, multidrug
      resistant, nontuberculous mycobacteria that are responsible for a wide spectrum
      of skin and soft tissue diseases, central nervous system infections, bacteremia,
      and ocular and other infections. M. abscessus complex is differentiated into 3
      subspecies: M. abscessus subsp. abscessus, M. abscessus subsp. massiliense, and
      M. abscessus subsp. bolletii. The 2 major subspecies, M. abscessus subsp.
      abscessus and M. abscessus subsp. massiliense, have different erm(41) gene
      patterns. This gene provides intrinsic resistance to macrolides, so the different
      patterns lead to different treatment outcomes. M. abscessus complex outbreaks
      associated with cosmetic procedures and nosocomial transmissions are not
      uncommon. Clarithromycin, amikacin, and cefoxitin are the current antimicrobial
      drugs of choice for treatment. However, new treatment regimens are urgently
      needed, as are rapid and inexpensive identification methods and measures to
      contain nosocomial transmission and outbreaks. 

PMID- 26295365
TI  - Postoperative cerebral glucose metabolism in pediatric patients receiving proton
      therapy for craniopharyngioma.
AB  - OBJECT The aim of the study was to document postoperative cerebral glucose
      distribution before proton therapy using F-18 fluorodeoxyglucose positron
      emission tomography (FDG PET) in children with craniopharyngioma. METHODS Between
      August 2011 and April 2014, 50 patients (20 males, 30 females) enrolled in a
      prospective trial for craniopharyngioma underwent FDG PET imaging before proton
      therapy. Proton therapy was delivered using doublescattered beams with a total
      prescribed dose of 54 cobalt gray equivalent. Tracer uptake in each of 63
      anatomical regions was computed after warping PET images to a 3D reference
      template in Talairach coordinates. Regional uptake was deemed significantly low
      or high if it exceeded age-corresponding 95% prediction intervals of the normal
      population. The reference group included 132 children with non-CNS-related
      diseases and normal-appearing cerebral FDG PET scans. RESULTS Median patient age
      at diagnosis was 8.5 years (range 2-18 years). Forty-eight patients underwent 1-4
      tumor-related surgeries before proton therapy, including placement of an Ommaya
      reservoir in 14 patients. Sixteen patients had symptomatic hydrocephalus that was
      treated with temporary (external ventricular drain, n = 16) or permanent CSF
      shunting (ventriculoperitoneal shunt, n = 1). The most commonly seen PET
      abnormalities in patients before proton therapy were significantly reduced uptake
      in subregions of the frontal lobe (often involving more than 1 gyrus), medial and
      ventral portions of the temporal lobe, cingulate gyrus, and caudate nucleus. A
      significantly high uptake was frequently observed on the contralateral side,
      including the superior, medial, and inferior temporal gyri and a large portion of
      the parietal lobe. Statistically significant predictor variables identified in
      the multivariate analysis for the extent of hypometabolism were sex (p = 0.005),
      hydrocephalus (p = 0.026), and the number of tumor-related surgeries (p = 0.017).
      CONCLUSIONS Postoperative FDG PET of patients with craniopharyngioma revealed
      metabolic abnormalities in specific regions of the brain. The ability to identify
      anatomical metabolic defects in individual patients facilitates the investigation
      of brain injury in children with craniopharyngioma.

PMID- 26295366
TI  - Ruptured pediatric cerebellopontine angle epidermoid cyst: a case report
      detailing radiographic evolution and clinical course.
AB  - Epidermoid cysts (ECs) are uncommon pediatric tumors that often occur in the
      cerebellopontine angle. Although cyst rupture is a recognized complication, the
      radiographic evolution of an EC following rupture and the resultant parenchymal
      brainstem edema have not been reported. The authors present the case of a 13-year
      old female with a newly diagnosed cerebellopontine angle EC who presented with
      worsening headaches, photophobia, and emesis. Magnetic resonance imaging
      demonstrated significant pericystic brainstem edema and mass effect with
      effacement of the fourth ventricle. Refractory symptoms prompted repeat imaging,
      revealing cyst enlargement and dense rim enhancement. Resection of the EC
      resolved both her symptoms and the brainstem edema. This case documents the
      radiographic evolution of EC rupture and subsequent clinical course.

PMID- 26295367
TI  - Protective activity of probiotic bacteria against 2-amino-3-methyl-3H-imidazo[4,5
      f]quinoline (IQ) and 2-amino-1-methyl-6-phenyl-1H-imidazo[4,5-b]pyridine (PhIP) -
      an in vitro study.
AB  - Heterocyclic aromatic amines (HAAs) are carcinogenic compounds present in a
      typical Western diet rich in thermally processed meat. These nutritional factors
      can modulate the cytotoxicity of faecal water (FW) and induce tumours in the
      human gastrointestinal tract. Supplementation with probiotics is promising in
      terms of reducing the harmful effects of HAAs in the human body. The aim of the
      study was in vitro assessment of the protective activity of the probiotic strains
      Lb. rhamnosus 0900, Lb. rhamnosus 0908, Lb. casei 0919 and Lb. casei DN 114001
      against IQ (2-amino-3-methyl-3H-imidazo[4,5-f]quinoline) and PhIP (2-amino-1
      methyl-6-phenyl-1H-imidazo[4,5-b]pyridine) after incubation with faeces from 15
      persons aged 4 months to 82 years (children, adults and the elderly). The highest
      mean cytotoxicity of FW was observed for the elderly (63.2% +/- 3.7%) and the
      lowest for children (28.0% +/- 9.5%), as estimated by a neutral red uptake assay.
      The probiotics lowered the average cytotoxicity of FW exposed to IQ or PhIP. The
      concentration of IQ and PhIP in FW was most effectively reduced by Lb. rhamnosus
      0900 (47.5%) and Lb. casei 0919 (45.8%), respectively, as determined by high 
      performance liquid chromatography. All the tested strains bound PhIP to a higher
      extent than IQ. In an alkaline comet assay, Lb. casei 0919 and Lb. rhamnosus 0908
      displayed the strongest protective effect against IQ and PhIP (up to 80%
      reduction of DNA damage). Also in a comet assay, Lb. rhamnosus 0908 exhibited
      antioxidative activity toward H2O2 and PhIP (up to 63% and 69.5% reduction of
      oxidative DNA damage, respectively). The protective activity of the probiotic
      strains was specific to a given person's FW, which implies the involvement of
      intestinal microbiota in the process. 

PMID- 26295368
TI  - Analysis of the Spectroscopic Aspects of Cationic Dye Basic Orange 21.
AB  - Spectroscopic properties of cationic dye basic orange 21 (BO21) in solutions, in
      solids, and within leukocytes were examined. Results obtained with solutions
      indicate that influence of variables such as pH, viscosity, salt composition, and
      various proteins on the absorption spectrum of BO21 is negligible. However, in
      the presence of heparin, a blue shift (484-465 nm) is observed, which is
      attributed to the aggregation of BO21 on the polyanion. Applying density
      functional theory demonstrates that in aqueous solutions (a) the formation of
      BO21 oligomers is thermodynamically favorable, they are oriented in an
      antiparallel dipolar arrangement, and their binding energies are lower than those
      of parallel dipolar arrangements, (b) association between BO21 aggregates and
      heparin is highly favorable, and (c) the blue shift is due to the mixing of pi ->
      pi* transitions caused by BO21 molecule stacking. However, when embedded in
      basophils, the absorption spectra of intracellular BO21 is extremely red-shifted,
      with two peaks (at 505 and 550 nm) found to be attributed to BO21 and the BO21
      heparin complex, respectively, which are intracellularly hosted in nonaqueous
      environments. Initial evidence of the ability to differentiate between leukocyte
      types by BO21 is presented. 

PMID- 26295371
TI  - Corrigendum.

PMID- 26295369
TI  - Deficiency of FcepsilonR1 Increases Body Weight Gain but Improves Glucose
      Tolerance in Diet-Induced Obese Mice.
AB  - Prior studies demonstrated increased plasma IgE in diabetic patients, but the
      direct participation of IgE in diabetes or obesity remains unknown. This study
      found that plasma IgE levels correlated inversely with body weight, body mass
      index, and body fat mass among a population of randomly selected obese women. IgE
      receptor FcepsilonR1-deficient (Fcer1a(-/-)) mice and diet-induced obesity (DIO)
      mice demonstrated that FcepsilonR1 deficiency in DIO mice increased food intake,
      reduced energy expenditure, and increased body weight gain but improved glucose
      tolerance and glucose-induced insulin secretion. White adipose tissue from
      Fcer1a(-/-) mice showed an increased expression of phospho-AKT, CCAAT/enhancer
      binding protein-alpha, peroxisome proliferator-activated receptor-gamma, glucose
      transporter-4 (Glut4), and B-cell lymphoma 2 (Bcl2) but reduced uncoupling
      protein 1 (UCP1) and phosphorylated c-Jun N-terminal kinase (JNK) expression,
      tissue macrophage accumulation, and apoptosis, suggesting that IgE reduces
      adipogenesis and glucose uptake but induces energy expenditure, adipocyte
      apoptosis, and white adipose tissue inflammation. In 3T3-L1 cells, IgE inhibited
      the expression of CCAAT/enhancer binding protein-alpha and peroxisome
      proliferator-activated receptor-gamma, and preadipocyte adipogenesis and induced
      adipocyte apoptosis. IgE reduced the 3T3-L1 cell expression of Glut4, phospho
      AKT, and glucose uptake, which concurred with improved glucose tolerance in
      Fcer1a(-/-) mice. This study established two novel pathways of IgE in reducing
      body weight gain in DIO mice by suppressing adipogenesis and inducing adipocyte
      apoptosis while worsening glucose tolerance by reducing Glut4 expression, glucose
      uptake, and insulin secretion. 

PMID- 26295370
TI  - Aging and Loss of Circulating 17beta-Estradiol Alters the Alternative Splicing of
      ERbeta in the Female Rat Brain.
AB  - Loss of circulating 17beta-estradiol (E2) that occurs during menopause can have
      detrimental effects on cognitive function. The efficacy of hormone replacement
      therapy declines as women become farther removed from the menopausal transition,
      yet the molecular mechanisms underlying this age-related switch in E2 efficacy
      are unknown. We hypothesized that aging and varying lengths of E2 deprivation
      alters the ratio of alternatively spliced estrogen receptor (ER)beta isoforms in
      the brain of female rats. Further, we tested whether changes in global
      transcriptional activity and splicing kinetics regulate the alternative splicing
      of ERbeta. Our results revealed brain region-specific changes in ERbeta
      alternative splicing in both aging and E2-deprivation paradigms and showed that
      ERbeta could mediate E2-induced alternative splicing. Global transcriptional
      activity, as measured by phosphorylated RNA polymerase II, was also regulated by
      age and E2 in specific brain regions. Finally, we show that inhibition of
      topoisomerase I resulted in increased ERbeta2 splice variant expression. 

PMID- 26295372
TI  - Rapid Assembly of Functionalized Hydrodibenzofurans via Semipinacol
      Rearrangements.
AB  - A distinct strategy via unprecedented semipinacol rearrangements for the
      synthesis of functionalized hydrodibenzofurans is reported. The versatile
      reactivity of benzofuran-3-one as a building block enabled the convergent
      coupling of simple starting materials and, thus, allowed for the facile variation
      of R group and the construction of hydrodibenzofurans with fused rings. 

PMID- 26295373
TI  - An Aggregation Advisor for Ligand Discovery.
AB  - Colloidal aggregation of organic molecules is the dominant mechanism for
      artifactual inhibition of proteins, and controls against it are widely deployed.
      Notwithstanding an increasingly detailed understanding of this phenomenon, a
      method to reliably predict aggregation has remained elusive. Correspondingly,
      active molecules that act via aggregation continue to be found in early discovery
      campaigns and remain common in the literature. Over the past decade, over 12
      thousand aggregating organic molecules have been identified, potentially enabling
      a precedent-based approach to match known aggregators with new molecules that may
      be expected to aggregate and lead to artifacts. We investigate an approach that
      uses lipophilicity, affinity, and similarity to known aggregators to advise on
      the likelihood that a candidate compound is an aggregator. In prospective
      experimental testing, five of seven new molecules with Tanimoto coefficients
      (Tc's) between 0.95 and 0.99 to known aggregators aggregated at relevant
      concentrations. Ten of 19 with Tc's between 0.94 and 0.90 and three of seven with
      Tc's between 0.89 and 0.85 also aggregated. Another three of the predicted
      compounds aggregated at higher concentrations. This method finds that 61 827 or
      5.1% of the ligands acting in the 0.1 to 10 MUM range in the medicinal chemistry
      literature are at least 85% similar to a known aggregator with these physical
      properties and may aggregate at relevant concentrations. Intriguingly, only 0.73%
      of all drug-like commercially available compounds resemble the known aggregators,
      suggesting that colloidal aggregators are enriched in the literature. As a
      percentage of the literature, aggregator-like compounds have increased 9-fold
      since 1995, partly reflecting the advent of high-throughput and virtual screens
      against molecular targets. Emerging from this study is an aggregator advisor
      database and tool ( http://advisor.bkslab.org ), free to the community, that may
      help distinguish between fruitful and artifactual screening hits acting by this
      mechanism. 

PMID- 26295374
TI  - Homosexuality and the Law: The Construction of Wolfenden Homonormativity in 1950s
      England.
AB  - This article analyses a television broadcast in England in 1957 in response to
      the Wolfenden Report (Wolfenden, 1957) into homosexuality and prostitution. Here
      I argue that those participants in the broadcast who are sympathetic with liberal
      reforms of the legislation on homosexuality utilize discourses related to
      normality and the public/private domains to discursively construct the Wolfenden
      homonormative male. In addition, I also show how, particularly through the trope
      of homonormativity, both the heterosexual and homosexual audiences are
      interpellated by the discourses exploited within the broadcast as publics whose
      subjectivities are reconfigured toward Wolfenden homonormativity. 

PMID- 26295376
TI  - Early Prediction of Response to Tyrosine Kinase Inhibitors by Quantification of
      EGFR Mutations in Plasma of NSCLC Patients.
AB  - INTRODUCTION: The potential to accurately quantify epidermal growth factor
      receptor (EGFR) mutations in plasma from non-small-cell lung cancer patients
      would enable more rapid and more frequent analyses to assess disease status;
      however, the utility of such analyses for clinical purposes has only recently
      started to explore. METHODS: Plasma samples were obtained from 69 patients with
      EGFR-mutated tumors and 21 negative control cases. EGFR mutations in plasma were
      analyzed by a standardized allele-specific polymerase chain reaction (PCR) test
      and ultra-deep next-generation sequencing (NGS). A semiquantitative index (SQI)
      was derived from dilutions of known EGFR mutation copy numbers. Clinical
      responses were evaluated by Response Evaluation Criteria in Solid Tumors 1.1
      criteria and expressed as percent tumor shrinkage. RESULTS: The sensitivity and
      specificity of the PCR test and NGS assay in plasma versus tissue were 72% versus
      100% and 74% versus 100%, respectively. Quantitative indices by the PCR test and
      NGS were significantly correlated (p < 0.001). EGFR testing at baseline and
      serially at 4 to 60 days during tyrosine kinase inhibitor therapy revealed a
      progressive decrease in SQI, starting from day 4, in 95% of cases. The rate of
      SQI decrease correlated with percent tumor shrinkage at 2 months (p < 0.0001); at
      14 days, it was more than 50% in 70% of patients (rapid responders). In two
      patients with slow response, an early increase in the circulating levels of the
      T790M mutation was observed. No early T790M mutations were seen in plasma samples
      of rapid responders. CONCLUSIONS: Quantification of EGFR mutations from plasma
      with a standardized PCR test is feasible. To our knowledge, this is the first
      study showing a strong correlation between the EGFR SQI in the first days of
      treatment and clinical response with relevant implications for patient
      management.

PMID- 26295375
TI  - The 2015 World Health Organization Classification of Tumors of the Thymus:
      Continuity and Changes.
AB  - This overview of the 4th edition of the World Health Organization (WHO)
      Classification of thymic tumors has two aims. First, to comprehensively list the
      established and new tumor entities and variants that are described in the new WHO
      Classification of thymic epithelial tumors, germ cell tumors, lymphomas,
      dendritic cell and myeloid neoplasms, and soft-tissue tumors of the thymus and
      mediastinum; second, to highlight major differences in the new WHO Classification
      that result from the progress that has been made since the 3rd edition in 2004 at
      immunohistochemical, genetic and conceptual levels. Refined diagnostic criteria
      for type A, AB, B1-B3 thymomas and thymic squamous cell carcinoma are given, and
      it is hoped that these criteria will improve the reproducibility of the
      classification and its clinical relevance. The clinical perspective of the
      classification has been strengthened by involving experts from radiology,
      thoracic surgery, and oncology; by incorporating state-of-the-art positron
      emission tomography/computed tomography images; and by depicting prototypic
      cytological specimens. This makes the thymus section of the new WHO
      Classification of Tumours of the Lung, Pleura, Thymus and Heart a valuable tool
      for pathologists, cytologists, and clinicians alike. The impact of the new WHO
      Classification on therapeutic decisions is exemplified in this overview for
      thymic epithelial tumors and mediastinal lymphomas, and future perspectives and
      challenges are discussed. 

PMID- 26295377
TI  - Pediatric Immunization Distress: A Cluster Analyses of Children's, Parents', and
      Nurses' Behaviors During the Anticipatory Phase.
AB  - OBJECTIVE: Using cluster analysis, we aimed to identify a typology of nurses',
      parents', and young children's behaviors during the anticipatory phase of
      pediatric immunizations to explore the associations between these different
      typologies and to determine whether these groups differed with respect to the
      child's procedural distress as rated by the child and the parents and with
      respect to the adults' self-rated distress. MATERIALS AND METHODS: Immunizations
      given by 23 nurses to 220 children aged 3 years and 10 months to 7 years were
      recorded with behaviors being scored according to Child-Adult Medical Procedure
      Interaction Scale-Revised, to which 3 new codes were added, and rated with a 6
      point Likert scale. Parents' and nurses' ratings of their own distress and of the
      child's distress, in addition to children's self-rating of distress were
      obtained. Nine adult and 12 child behavioral codes were submitted for cluster
      analysis. RESULTS: A solution with 4 clusters for children, 5 clusters for
      parents, and 5 clusters for nurses was retained. Our results show high
      consistency between child and adult clusters. During the anticipatory phase, less
      distressed children, characterized by either low activity or high coping,
      interacted with adults who showed low activity or high coping support patterns.
      More distressed children, characterized by resistance and behavioral distress,
      interacted with adults who displayed either low activity or less efficient
      support behaviors, such as reassurance and criticism. DISCUSSION: The results
      confirm previous dimensional studies and add relevant knowledge concerning
      typologies of participant behaviors that may be useful in understanding such
      behaviors and in helping providers in their management of child immunizations.

PMID- 26295378
TI  - Prevalence and Correlates of Suicidal Thoughts and Suicide Attempts in People
      Prescribed Pharmaceutical Opioids for Chronic Pain.
AB  - OBJECTIVES: The main objectives of the paper were (1) to examine the prevalence
      of suicidality in a large community-based chronic pain sample taking prescribed
      opioids for chronic pain; and (2) to examine general and pain-specific factors
      that predict such ideation, and the transition from ideation to making a suicide
      attempt (ideation-to-action). MATERIALS AND METHODS: Baseline data from the Pain
      and Opioids IN Treatment (POINT) study with a cohort of 1514 community-based
      people prescribed opioids for chronic noncancer pain across Australia. RESULTS:
      Past 12-month suicidal ideation was reported by 36.5% of the cohort and 16.4% had
      made a lifetime suicide attempt (2.5% in the last 12 mo), after the onset of
      their pain condition. Suicidal ideation in the past 12 months was independently
      associated with a past suicide attempt [adjusted odds ratio (AOR)=4.82; 95%
      confidence interval, 2.43-9.56] and past 12-month depression (AOR=4.07, 95%
      confidence interval, 1.88-8.78). Only a lower pain self-efficacy score was
      independently associated with past 12-month ideation-to-action (AOR=0.98,
      95%CI0.88-0.99). Notably, only general-suicide risk factors were associated with
      12-month suicidal ideation; but for past year ideation-to-action, pain-specific
      factors also had independent associations. DISCUSSION: The study is one of the
      first to comprehensively examine general and pain-specific risk factors for
      suicidality in a large chronic pain sample in which suicidal ideation was common.
      A low pain self-efficacy score was the only factor independently associated past
      12-month ideation-to-action.

PMID- 26295379
TI  - The SPADE Symptom Cluster in Primary Care Patients With Chronic Pain.
AB  - OBJECTIVES: Sleep disturbance, pain, anxiety, depression, and low energy/fatigue,
      the SPADE pentad, are the most prevalent and co-occurring symptoms in the general
      population and clinical practice. Co-occurrence of SPADE symptoms may produce
      additive impairment and negatively affect treatment response, potentially
      undermining patients' health and functioning. The purpose of this paper is to
      determine: (1) prevalence and comorbidity (ie, clustering) of SPADE symptoms; (2)
      internal reliability and construct validity of a composite SPADE symptom score
      derived from the Patient-Reported Outcomes Measurement Information System
      (PROMIS) measures; and (3) whether improvement in somatic symptom burden
      represented by a composite score predicted subsequent measures of functional
      status at 3 and 12 months follow-up. METHODS: Secondary analysis of data from the
      Stepped Care to Optimize Pain care Effectiveness study, a randomized trial of a
      collaborative care intervention for Veterans with chronic pain. RESULTS: Most
      patients had multiple SPADE symptoms; only 9.6% of patients were monosymptomatic.
      The composite PROMIS symptom score had good internal reliability (Cronbach's
      alpha=0.86) and construct validity and strongly correlated with multiple measures
      of functional status; improvement in the composite score significantly correlated
      with higher scores for 5 of 6 functional status outcomes. The standardized error
      of measurement (SEM) for the composite T-score was 2.84, suggesting a 3-point
      difference in an individual's composite score may be clinically meaningful.
      DISCUSSION: Brief PROMIS measures may be useful in evaluating SPADE symptoms and
      overall symptom burden. Because symptom burden may predict functional status
      outcomes, better identification and management of comorbid symptoms may be
      warranted.

PMID- 26295380
TI  - Pulse Transit Time as a Predictor of the Efficacy of a Celiac Plexus Block in
      Patients With Chronic Intractable Abdominal Pain.
AB  - OBJECTIVE: There is no well-defined predictor of satisfactory pain relief after
      celiac plexus block (CPB) at the early stage of treatment. This study evaluated
      whether measurement of the electrocardiographic R-wave and the arrival time of
      the pulses at the toe pulse transit time (E-T PTT) can be an early predictor of
      pain response and success of CPB in patients with chronic intractable visceral
      pain. METHODS: Twelve patients aged between 20 and 80 years who underwent CPB for
      treatment of chronic intractable cancer-related abdominal pain were included. A
      successful CPB was determined as a >50% decrease on the numerical rating scale
      measured 24 hours after the procedure. The E-T PTT at baseline and at 5, 10, 20,
      and 30 minutes after the injection of local anesthetic was measured as the time
      between the R-wave on the electrocardiogram and the peak point of the
      corresponding plethysmogram wave from the ipsilateral great toe. The change in
      the E-T PTT that was predictive of a successful CPB was analyzed using receiver
      operating characteristic curve analysis. RESULTS: A CPB was successful in 9 of 12
      cases; the dE-T PTT5/E-T PTT0 of the success group was 6.84%+/-5.04% versus
      0.72%+/-0.78% in the failure group (P=0.021). The mean E-T PTTx differed
      significantly between timepoints (F=9.313, P=0.014) and between the success and
      failure groups (P<0.01). The best value of dE-T PTT5/E-T PTT0 indicating a
      successful CPB, estimated by receiver operating characteristic curve analysis,
      was 2.30% (sensitivity 88.9%, specificity 100%). The area under the curve was 96%
      (95% confidence interval, 85.7%-100%). CONCLUSIONS: Prolongation of E-T PTT at 5
      minutes after CPB correlates closely with a significant analgesic effect.

PMID- 26295381
TI  - Acute Complications of Myocardial Infarction in the Current Era: Diagnosis and
      Management.
AB  - Coronary heart disease is a major cause of mortality and morbidity worldwide. The
      incidence of mechanical complications of acute myocardial infarction (AMI) has
      gone down to less than 1% since the advent of percutaneous coronary intervention,
      but although mortality resulting from AMI has gone down in recent years, the
      burden remains high. Mechanical complications of AMI include cardiogenic shock,
      free wall rupture, ventricular septal rupture, acute mitral regurgitation, and
      right ventricular infarction. Detailed knowledge of the complications and their
      risk factors can help clinicians in making an early diagnosis. Prompt diagnosis
      with appropriate medical therapy and timely surgical intervention are necessary
      for favorable outcomes. 

PMID- 26295382
TI  - Titanium-catalyzed multicomponent couplings: efficient one-pot syntheses of
      nitrogen heterocycles.
AB  - Nitrogen-based heterocycles are important frameworks for pharmaceuticals, natural
      products, organic dyes for solar cells, and many other applications. Catalysis
      for the formation of heterocyclic scaffolds, like many C-C and C-N bond-forming
      reactions, has focused on the use of rare, late transition metals like palladium
      and gold. Our group is interested in the use of Earth-abundant catalysts based on
      titanium to generate heterocycles using multicomponent coupling strategies, often
      in one-pot reactions. To be of maximal utility, the catalysts need to be easily
      prepared from inexpensive reagents, and that has been one guiding principle in
      the research. For this purpose, a series of easily prepared pyrrole-based ligands
      has been developed. Titanium imido complexes are known to catalyze the
      hydroamination of alkynes, and this reaction has been used to advantage in the
      production of alpha,beta-unsaturated imines from 1,3-enynes and pyrroles from 1,4
      diynes. Likewise, catalyst design can be used to find complexes applicable to
      hydrohydrazination, coupling of a hydrazine and alkyne, which is a method for the
      production of hydrazones. Many of the hydrazones synthesized are converted to
      indoles through Fischer cyclization by addition of a Lewis acid. However, more
      complex products are available in a single catalytic cycle through coupling of
      isonitriles, primary amines, and alkynes to give tautomers of 1,3-diimines,
      iminoamination (IA). The products of IA are useful intermediates for the one-pot
      synthesis of pyrazoles, pyrimidines, isoxazoles, quinolines, and 2-amino-3
      cyanopyridines. The regioselectivity of the reactions is elucidated in some
      detail for some of these heterocycles. The 2-amino-3-cyanopyridines are
      synthesized through isolable intermediates, 1,2-dihydro-2-iminopyridines, which
      undergo Dimroth rearrangement driven by aromatization of the pyridine ring; the
      proposed mechanism of the reaction is discussed. The IA-based heterocyclic
      syntheses can be accomplished start to finish (catalyst generation to
      heterocyclic synthesis) in a single vessel. The catalyst can be formed in situ
      from commercially available Ti(NMe2)4 and the protonated form of the ligand.
      Then, the primary amine, alkyne, and isonitrile are added to the flask, and the
      IA product is synthesized. The volatiles are removed (if necessary), and the next
      reagent is added. A brief video showing the process for the simple heterocycle 4
      phenylpyrazole from phenylacetylene, cyclohexylamine, tert-butylisonitrile, and
      hydrazine hydrate is included. Further development in this field will unlock new,
      efficient reactions for the production of carbon-carbon and carbon-nitrogen
      bonds. As an example of such a process recently discovered, a catalyst for the
      regioselective production of pyrazoles in a single step from terminal alkynes,
      hydrazines, and cyclohexylisonitrile is discussed. Using titanium catalysis, many
      heterocyclic cores can be accessed easily and efficiently. Further, the early
      metal chemistry described is often orthogonal to late metal-based reactions,
      which use substrates like aryl halides, silyl groups, boryl groups, and so forth.
      As a result, earth-abundant and nontoxic titanium can fulfill important roles in
      the synthesis of useful classes of compounds like heterocycles. 

PMID- 26295383
TI  - Laccase Gene Expression and Vinasse Biodegradation by Trametes hirsuta Strain Bm
      2.
AB  - Vinasse is the dark-colored wastewater that is generated by bioethanol
      distilleries from feedstock molasses. The vinasse that is generated from molasses
      contains high amounts of pollutants, including phenolic compounds and
      melanoindin. The goal of this work was to study the expression of laccase genes
      in the Trametes hirsuta strain Bm-2, isolated in Yucatan, Mexico, in the presence
      of phenolic compounds, as well as its effectiveness in removing colorants from
      vinasse. In the presence of all phenolic compounds tested (guaiacol, ferulic
      acid, and vanillic acid), increased levels of laccase-encoding mRNA were
      observed. Transcript levels in the presence of guaiacol were 40 times higher than
      those in the control. The lcc1 and lcc2 genes of T. hirsuta were differentially
      expressed; guaiacol and vanillin induced the expression of both genes, whereas
      ferulic acid only induced the expression of lcc2. The discoloration of vinasse
      was concomitant with the increase in laccase activity. The highest value of
      enzyme activity (2543.7 U/mL) was obtained in 10% (v/v) vinasse, which
      corresponded to a 69.2% increase in discoloration. This study demonstrates the
      potential of the Bm-2 strain of T. hirsuta for the biodegradation of vinasse. 

PMID- 26295384
TI  - Mitochondrial DNA Variation Reveals a Sharp Genetic Break within the Distribution
      of the Blue Land Crab Cardisoma guanhumi in the Western Central Atlantic.
AB  - The blue land crab Cardisoma guanhumi is widely distributed throughout tropical
      and subtropical estuarine regions in the Western Central Atlantic (WCA). Patterns
      of population genetic structure and historical demographics of the species were
      assessed by mtDNA control region sequence analysis to examine the connectivity
      among five populations (n = 97) within the region for future conservation
      strategies and decision-making of fishery management. A total of 234 polymorphic
      nucleotides were revealed within the sequence region, which have defined 93
      distinct haplotypes. No dominant mtDNA haplotypes were found but instead a
      distribution of a few low-frequency recurrent haplotypes with a large number of
      singletons. A NJ-tree and a median-joining haplotype network revealed two
      distinct clusters, corresponding to individuals from estuaries located along the
      Caribbean Sea and Brazilian waters, respectively. AMOVA and FST statistics
      supported the hypothesis that two main geographic regions exists.
      Phylogeographical discontinuity was further demonstrated by the Bayesian
      assignment analysis and a significant pattern of isolation-by-distance.
      Additionally, tests of neutral evolution and analysis of mismatch distribution
      indicate a complex demographic history in the WCA, which corresponds to
      bottleneck and subsequent population growth. Overall, a sharp genetic break
      between Caribbean and Brazilian populations raised concerns over the conservation
      status of the blue land crab. 

PMID- 26295385
TI  - Characterization of the Sublimation and Vapor Pressure of 2-(2-Nitrovinyl) Furan
      (G-0) Using Thermogravimetric Analysis: Effects of Complexation with
      Cyclodextrins.
AB  - In the present work, the sublimation of crystalline solid 2-(2-nitrovinyl) furan
      (G-0) in the temperature range of 35 to 60  degrees C (below the melting point of
      the drug) was studied using thermogravimetric analysis (TGA). The sublimated
      product was characterized using Fourier-transformed-infrared spectroscopy (FT-IR)
      and thin layer chromatography (TLC). The sublimation rate at each temperature was
      obtained using the slope of the linear regression model and followed apparent
      zero-order kinetics. The sublimation enthalpy from 35 to 60  degrees C was
      obtained from the Eyring equation. The Guckel method was used to estimate the
      sublimation rate and vapor pressure at 25  degrees C. Physical mixtures, kneaded
      and freeze-dried complexes were prepared with 2-hydroxypropyl-beta-cyclodextrin
      (HP-beta-CD) and sulfobutyl ether-beta-cyclodextrin (SBE-beta-CD) and analyzed
      using isothermal TGA at 50  degrees C. The complexation contributed to reducing
      the sublimation process. The best results were achieved using freeze-dried
      complexes with both cyclodextrins. 

PMID- 26295386
TI  - Genetic Polymorphisms of Glutathione-Related Enzymes (GSTM1, GSTT1, and GSTP1)
      and Schizophrenia Risk: A Meta-Analysis.
AB  - The association between polymorphisms of glutathione-related enzyme (GST) genes
      and the risk of schizophrenia has been investigated in many published studies.
      However, their results were inconclusive. Therefore, we performed a meta-analysis
      to explore the association between the GSTM1, GSTT1, and GSTP1 polymorphisms and
      the risk of schizophrenia. Twelve case-control studies were included in this meta
      analysis. The odds ratio (OR) and 95% confidence interval (95% CI) were used to
      investigate the strength of the association. Our meta-analysis results revealed
      that GSTM1, GSTT1, and GSTP1 polymorphisms were not related to risk of
      schizophrenia (p > 0.05 in each model). Further analyses based on ethnicity, GSTM
      polymorphism showed weak association with schizophrenia in East Asian population
      (OR = 1.314, 95% CI = 1.025-1.684, p = 0.031). In conclusion, our meta-analysis
      indicated the GSTM1 polymorphism may be the only genetic risk factor for
      schizophrenia in East Asian population. However, more meta-analysis with a larger
      sample size were needed to provide more precise evidence. 

PMID- 26295387
TI  - Preliminary Evidence on the Diagnostic and Molecular Role of Circulating Soluble
      EGFR in Non-Small Cell Lung Cancer.
AB  - Assessment of biological diagnostic factors providing clinically-relevant
      information to guide physician decision-making are still needed for diseases with
      poor outcomes, such as non-small cell lung cancer (NSCLC). Epidermal growth
      factor receptor (EGFR) is a promising molecule in the clinical management of
      NSCLC. While the EGFR transmembrane form has been extensively investigated in
      large clinical trials, the soluble, circulating EGFR isoform (sEGFR), which may
      have a potential clinical use, has rarely been considered. This study
      investigates the use of sEGFR as a potential diagnostic biomarker for NSCLC and
      also characterizes the biological function of sEGFR to clarify the molecular
      mechanisms involved in the course of action of this protein. Plasma sEGFR levels
      from a heterogeneous cohort of 37 non-advanced NSCLC patients and 54 healthy
      subjects were analyzed by using an enzyme-linked immunosorbent assay. The
      biological function of sEGFR was analyzed in vitro using NSCLC cell lines,
      investigating effects on cell proliferation and migration. We found that plasma
      sEGFR was significantly decreased in the NSCLC patient group as compared to the
      control group (median value: 48.6 vs. 55.6 ng/mL respectively; p = 0.0002).
      Moreover, we demonstrated that sEGFR inhibits growth and migration of NSCLC cells
      in vitro through molecular mechanisms that included perturbation of EGF/EGFR cell
      signaling and holoreceptor internalization. These data show that sEGFR is a
      potential circulating biomarker with a physiological protective role, providing a
      first approach to the functional role of the soluble isoform of EGFR. However,
      the impact of these data on daily clinical practice needs to be further
      investigated in larger prospective studies. 

PMID- 26295388
TI  - Structural Features of the ATP-Binding Cassette (ABC) Transporter ABCA3.
AB  - In this review we reported and discussed the structural features of the ATP
      Binding Cassette (ABC) transporter ABCA3 and how the use of bioinformatics tools
      could help researchers to obtain a reliable structural model of this important
      transporter. In fact, a model of ABCA3 is still lacking and no crystallographic
      structures (of the transporter or of its orthologues) are available. With the
      advent of next generation sequencing, many disease-causing mutations have been
      discovered and many more will be found in the future. In the last few years,
      ABCA3 mutations have been reported to have important pediatric implications.
      Thus, clinicians need a reliable structure to locate relevant mutations of this
      transporter and make genotype/phenotype correlations of patients affected by
      ABCA3-related diseases. In conclusion, we strongly believe that the model
      preliminarily generated by these novel bioinformatics tools could be the starting
      point to obtain more refined models of the ABCA3 transporter. 

PMID- 26295389
TI  - Engineering of Self-Assembled Fibronectin Matrix Protein and Its Effects on
      Mesenchymal Stem Cells.
AB  - Fibronectin (FN) contributes to cell adhesion, proliferation, and differentiation
      in various cell types. To enhance the activity of fibronectin at the sites of
      focal adhesion, we engineered a novel recombinant fibronectin (FNIII10) fragment
      connected to the peptide amphiphile sequence (PA), LLLLLLCCCGGDS. In this study,
      the effects of FNIII10-PA on rat mesenchymal stem cells (rMSCs) were compared
      with those of FNIII10. FNIII10-PA showed the prominent protein adhesion activity.
      In addition, FNIII10-PA showed a significantly higher effect on adhesion,
      proliferation, and differentiation of rMSCs than FNIII10. Taken together, the
      FNIII10-containing self-assembled sequence enhanced rMSCs adhesion,
      proliferation, and differentiation. 

PMID- 26295393
TI  - Influence of Errors in Tactile Sensors on Some High Level Parameters Used for
      Manipulation with Robotic Hands.
AB  - Tactile sensors suffer from many types of interference and errors like crosstalk,
      non-linearity, drift or hysteresis, therefore calibration should be carried out
      to compensate for these deviations. However, this procedure is difficult in
      sensors mounted on artificial hands for robots or prosthetics for instance, where
      the sensor usually bends to cover a curved surface. Moreover, the calibration
      procedure should be repeated often because the correction parameters are easily
      altered by time and surrounding conditions. Furthermore, this intensive and
      complex calibration could be less determinant, or at least simpler. This is
      because manipulation algorithms do not commonly use the whole data set from the
      tactile image, but only a few parameters such as the moments of the tactile
      image. These parameters could be changed less by common errors and interferences,
      or at least their variations could be in the order of those caused by accepted
      limitations, like reduced spatial resolution. This paper shows results from
      experiments to support this idea. The experiments are carried out with a high
      performance commercial sensor as well as with a low-cost error-prone sensor built
      with a common procedure in robotics. 

PMID- 26295392
TI  - Hepatocellular Carcinoma in Patients with a Sustained Response to Anti-Hepatitis
      C Therapy.
AB  - Hepatocellular carcinoma (HCC) is a common, life-threatening complication of
      longstanding infection with the hepatitis C virus (HCV), likely a consequence of
      the direct oncogenic activity of the virus cooperating with liver cell
      inflammation in transforming the liver into a mitogenic and mutagenic
      environment. The achievement of a sustained virological response (SVR) to
      interferon-based therapies has been shown to benefit the course of hepatitis C in
      terms of reduced rates of liver-related complications and mortality from all
      causes. Interestingly, while achievement of an SVR is associated with a
      negligible risk of developing clinical decompensation over the years, the risk of
      HCC is not fully abrogated following HCV clearance, but it remains the dominant
      complication in all SVR populations. The factors accounting for such a residual
      risk of HCC in SVR patients are not fully understood, yet the persistence of the
      subverted architecture of the liver, diabetes and alcohol abuse are likely
      culprits. In the end, the risk of developing an HCC in SVR patients is attenuated
      by 75% compared to non-responders or untreated patients, whereas responders who
      develop an HCC may be stratified in different categories of HCC risk by a score
      based on the same demographic and liver disease-based variables, such as those
      that predict liver cancer in viremic patients. All in all, this prevents full
      understanding of those factors that drive HCC risk once HCV has been eradicated.
      Here, we critically review current understanding of HCC in SVR patients focusing
      on factors that predict residual risk of HCC among these patients and providing a
      glimpse of the expected benefits of new anti-HCV regimens based on direct
      antiviral agents. 

PMID- 26295394
TI  - Use of Low-Cost Acquisition Systems with an Embedded Linux Device for Volcanic
      Monitoring.
AB  - This paper describes the development of a low-cost multiparameter acquisition
      system for volcanic monitoring that is applicable to gravimetry and geodesy, as
      well as to the visual monitoring of volcanic activity. The acquisition system was
      developed using a System on a Chip (SoC) Broadcom BCM2835 Linux operating system
      (based on DebianTM) that allows for the construction of a complete monitoring
      system offering multiple possibilities for storage, data-processing,
      configuration, and the real-time monitoring of volcanic activity. This
      multiparametric acquisition system was developed with a software environment, as
      well as with different hardware modules designed for each parameter to be
      monitored. The device presented here has been used and validated under different
      scenarios for monitoring ocean tides, ground deformation, and gravity, as well as
      for monitoring with images the island of Tenerife and ground deformation on the
      island of El Hierro. 

PMID- 26295391
TI  - Spatial Regulation of Root Growth: Placing the Plant TOR Pathway in a
      Developmental Perspective.
AB  - Plant cells contain specialized structures, such as a cell wall and a large
      vacuole, which play a major role in cell growth. Roots follow an organized
      pattern of development, making them the organs of choice for studying the spatio
      temporal regulation of cell proliferation and growth in plants. During root
      growth, cells originate from the initials surrounding the quiescent center,
      proliferate in the division zone of the meristem, and then increase in length in
      the elongation zone, reaching their final size and differentiation stage in the
      mature zone. Phytohormones, especially auxins and cytokinins, control the dynamic
      balance between cell division and differentiation and therefore organ size. Plant
      growth is also regulated by metabolites and nutrients, such as the sugars
      produced by photosynthesis or nitrate assimilated from the soil. Recent
      literature has shown that the conserved eukaryotic TOR (target of rapamycin)
      kinase pathway plays an important role in orchestrating plant growth. We will
      summarize how the regulation of cell proliferation and cell expansion by
      phytohormones are at the heart of root growth and then discuss recent data
      indicating that the TOR pathway integrates hormonal and nutritive signals to
      orchestrate root growth. 

PMID- 26295390
TI  - The Incremental Induction of Neuroprotective Properties by Multiple Therapeutic
      Strategies for Primary and Secondary Neural Injury.
AB  - Neural diseases including injury by endogenous factors, traumatic brain injury,
      and degenerative neural injury are eventually due to reactive oxygen species
      (ROS). Thus ROS generation in neural tissues is a hallmark feature of numerous
      forms of neural diseases. Neural degeneration and the neural damage process is
      complex, involving a vast array of tissue structure,
      transcriptional/translational, electrochemical, metabolic, and functional events
      within the intact neighbors surrounding injured neural tissues. During aging,
      multiple changes involving physical, chemical, and biochemical processes occur
      from the molecular to the morphological levels in neural tissues. Among many
      recommended therapeutic candidates, melatonin also plays a role in protecting the
      nervous system from anti-inflammation and efficiently safeguards neuronal cells
      via antioxidants and other endogenous/exogenous beneficial factors. Therefore,
      given the wide range of mechanisms responsible for neuronal damage, multi-action
      drugs or therapies for the treatment of neural injury that make use of two or
      more agents and target several pathways may have greater efficacy in promoting
      functional recovery than a single therapy alone. 

PMID- 26295395
TI  - In Situ 3D Segmentation of Individual Plant Leaves Using a RGB-D Camera for
      Agricultural Automation.
AB  - In this paper, we present a challenging task of 3D segmentation of individual
      plant leaves from occlusions in the complicated natural scene. Depth data of
      plant leaves is introduced to improve the robustness of plant leaf segmentation.
      The low cost RGB-D camera is utilized to capture depth and color image in fields.
      Mean shift clustering is applied to segment plant leaves in depth image. Plant
      leaves are extracted from the natural background by examining vegetation of the
      candidate segments produced by mean shift. Subsequently, individual leaves are
      segmented from occlusions by active contour models. Automatic initialization of
      the active contour models is implemented by calculating the center of divergence
      from the gradient vector field of depth image. The proposed segmentation scheme
      is tested through experiments under greenhouse conditions. The overall
      segmentation rate is 87.97% while segmentation rates for single and occluded
      leaves are 92.10% and 86.67%, respectively. Approximately half of the
      experimental results show segmentation rates of individual leaves higher than
      90%. Nevertheless, the proposed method is able to segment individual leaves from
      heavy occlusions. 

PMID- 26295396
TI  - Predicting Blood Lactate Concentration and Oxygen Uptake from sEMG Data during
      Fatiguing Cycling Exercise.
AB  - This article presents a study of the relationship between electromyographic (EMG)
      signals from vastus lateralis, rectus femoris, biceps femoris and semitendinosus
      muscles, collected during fatiguing cycling exercises, and other physiological
      measurements, such as blood lactate concentration and oxygen consumption. In
      contrast to the usual practice of picking one particular characteristic of the
      signal, e.g., the median or mean frequency, multiple variables were used to
      obtain a thorough characterization of EMG signals in the spectral domain. Based
      on these variables, linear and non-linear (random forest) models were built to
      predict blood lactate concentration and oxygen consumption. The results showed
      that mean and median frequencies are sub-optimal choices for predicting these
      physiological quantities in dynamic exercises, as they did not exhibit
      significant changes over the course of our protocol and only weakly correlated
      with blood lactate concentration or oxygen uptake. Instead, the root mean square
      of the original signal and backward difference, as well as parameters describing
      the tails of the EMG power distribution were the most important variables for
      these models. Coefficients of determination ranging from R(2) = 0:77 to R(2) =
      0:98 (for blood lactate) and from R(2) = 0:81 to R(2) = 0:97 (for oxygen uptake)
      were obtained when using random forest regressors. 

PMID- 26295397
TI  - A Novel Thermal Sensor for the Sensitive Measurement of Chemical Oxygen Demand.
AB  - A novel rapid methodology for determining the chemical oxygen demand (COD) based
      on a thermal sensor with a flow injection analysis system was proposed and
      experimentally validated. The ability of this sensor to detect and monitor COD
      was based on the degree of enthalpy increase when sodium hypochlorite reacted
      with the organic content in water samples. The measurement results were
      correlated with COD and were compared against the conventional method using
      potassium dichromate. The assay required only 5-7 min rather than the 2 h
      required for evaluation by potassium dichromate. The linear range was 5-1000 mg/L
      COD, and the limit of detection was very low, 0.74 mg/L COD. Moreover, this
      method exhibited high tolerance to chloride ions; 0.015 mol/L chloride ions had
      no influence on the response. Finally, the sensor was used to detect the COD of
      different water samples; the results were verified by the standard dichromate
      method. 

PMID- 26295399
TI  - Belief Function Based Decision Fusion for Decentralized Target Classification in
      Wireless Sensor Networks.
AB  - Decision fusion in sensor networks enables sensors to improve classification
      accuracy while reducing the energy consumption and bandwidth demand for data
      transmission. In this paper, we focus on the decentralized multi-class
      classification fusion problem in wireless sensor networks (WSNs) and a new simple
      but effective decision fusion rule based on belief function theory is proposed.
      Unlike existing belief function based decision fusion schemes, the proposed
      approach is compatible with any type of classifier because the basic belief
      assignments (BBAs) of each sensor are constructed on the basis of the
      classifier's training output confusion matrix and real-time observations. We also
      derive explicit global BBA in the fusion center under Dempster's combinational
      rule, making the decision making operation in the fusion center greatly
      simplified. Also, sending the whole BBA structure to the fusion center is
      avoided. Experimental results demonstrate that the proposed fusion rule has
      better performance in fusion accuracy compared with the naive Bayes rule and
      weighted majority voting rule. 

PMID- 26295398
TI  - Considerations on Circuit Design and Data Acquisition of a Portable Surface
      Plasmon Resonance Biosensing System.
AB  - The aim of this study was to develop a circuit for an inexpensive portable
      biosensing system based on surface plasmon resonance spectroscopy. This portable
      biosensing system designed for field use is characterized by a special structure
      which consists of a microfluidic cell incorporating a right angle prism
      functionalized with a biomolecular identification membrane, a laser line
      generator and a data acquisition circuit board. The data structure, data memory
      capacity and a line charge-coupled device (CCD) array with a driving circuit for
      collecting the photoelectric signals are intensively focused on and the high
      performance analog-to-digital (A/D) converter is comprehensively evaluated. The
      interface circuit and the photoelectric signal amplifier circuit are first
      studied to obtain the weak signals from the line CCD array in this experiment.
      Quantitative measurements for validating the sensitivity of the biosensing system
      were implemented using ethanol solutions of various concentrations indicated by
      volume fractions of 5%, 8%, 15%, 20%, 25%, and 30%, respectively, without a
      biomembrane immobilized on the surface of the SPR sensor. The experiments
      demonstrated that it is possible to detect a change in the refractive index of an
      ethanol solution with a sensitivity of 4.99838 * 10(5) DeltaRU/RI in terms of the
      changes in delta response unit with refractive index using this SPR biosensing
      system, whereby the theoretical limit of detection of 3.3537 * 10(-5) refractive
      index unit (RIU) and a high linearity at the correlation coefficient of 0.98065.
      The results obtained from a series of tests confirmed the practicality of this
      cost-effective portable SPR biosensing system. 

PMID- 26295400
TI  - The Mucus of Actinia equina (Anthozoa, Cnidaria): An Unexplored Resource for
      Potential Applicative Purposes.
AB  - The mucus produced by many marine organisms is a complex mixture of proteins and
      polysaccharides forming a weak watery gel. It is essential for vital processes
      including locomotion, navigation, structural support, heterotrophic feeding and
      defence against a multitude of environmental stresses, predators, parasites, and
      pathogens. In the present study we focused on mucus produced by a benthic
      cnidarian, the sea anemone Actinia equina (Linnaeus, 1758) for preventing burial
      by excess sedimentation and for protection. We investigated some of the physico
      chemical properties of this matrix such as viscosity, osmolarity, electrical
      conductivity, protein, carbohydrate, and total lipid contents. Some biological
      activities such as hemolytic, cytotoxic, and antibacterial lysozyme-like
      activities were also studied. The A. equina mucus is mainly composed by water
      (96.2% +/- 0.3%), whereas its dry weight is made of 24.2% +/- 1.3% proteins and
      7.8% +/- 0.2% carbohydrates, with the smallest and largest components referable
      to lipids (0.9%) and inorganic matter (67.1%). The A. equina mucus matrix
      exhibited hemolytic activity on rabbit erythrocytes, cytotoxic activity against
      the tumor cell line K562 (human erythromyeloblastoid leukemia) and antibacterial
      lysozyme-like activity. The findings from this study improve the available
      information on the mucus composition in invertebrates and have implications for
      future investigations related to exploitation of A. equina and other sea
      anemones' mucus as a source of bioactive compounds of high pharmaceutical and
      biotechnological interest. 

PMID- 26295402
TI  - Biosurfactant Production by Bacillus salmalaya for Lubricating Oil Solubilization
      and Biodegradation.
AB  - This study investigated the capability of a biosurfactant produced by a novel
      strain of Bacillus salmalaya to enhance the biodegradation rates and
      bioavailability of organic contaminants. The biosurfactant produced by cultured
      strain 139SI showed high physicochemical properties and surface activity in the
      selected medium. The biosurfactant exhibited a high emulsification index and a
      positive result in the drop collapse test, with the results demonstrating the
      wetting activity of the biosurfactant and its potential to produce surface-active
      molecules. Strain 139SI can significantly reduce the surface tension (ST) from
      70.5 to 27 mN/m, with a critical micelle concentration of 0.4%. Moreover,
      lubricating oil at 2% (v/v) was degraded on Day 20 (71.5). Furthermore, the
      biosurfactant demonstrated high stability at different ranges of salinity, pH,
      and temperature. Overall, the results indicated the potential use of B. salmalaya
      139SI in environmental remediation processes. 

PMID- 26295403
TI  - Epidemiological Characteristics of Work-Related Ocular Trauma in Southwest Region
      of China.
AB  - PURPOSE: To determine the epidemiological characteristics of work-related eye
      injury in representative southwest region of China. METHODS: Patients with eye
      injuries treated at the Ninth People's Hospital of Chongqing from 1 January 2014
      to 31 December 2014 were included in the current study. All patients completed a
      comprehensive examination and interview. Demographic characteristics and injury
      details were recorded. The International Classification of Diseases (ICD-10) and
      Birmingham Eye Trauma Terminology (BETT) were used. RESULTS: The average age of
      eye injury patients was 37.52 years and the majority were male. Among the 1055
      total patients, approximately 42.9% of the injuries were work-related. The
      highest proportion of occupational eye trauma was observed in the group between
      36 and 45 years of age. Occupational ocular trauma occurred more frequently in
      summer, with most from 16:00 to 18:00. Metal was the most common injury cause.
      Foreign body on external eye was the most common diagnosis. Workers in the
      manufacturing industry without pre-work safety training or eye protection were
      far more likely to suffer from occupational ocular trauma than those with
      training and protection. CONCLUSIONS: This study provides insight into the
      epidemiological characteristics of occupational ocular trauma in southwest region
      of China. The current findings might be considered as a baseline for future
      research on regional work-related eye injuries. Our findings will provide
      valuable information for further development of preventive strategies.

PMID- 26295401
TI  - Silaffins in Silica Biomineralization and Biomimetic Silica Precipitation.
AB  - Biomineralization processes leading to complex solid structures of inorganic
      material in biological systems are constantly gaining attention in biotechnology
      and biomedical research. An outstanding example for biomineral morphogenesis is
      the formation of highly elaborate, nano-patterned silica shells by diatoms. Among
      the organic macromolecules that have been closely linked to the tightly
      controlled precipitation of silica in diatoms, silaffins play an extraordinary
      role. These peptides typically occur as complex posttranslationally modified
      variants and are directly involved in the silica deposition process in diatoms.
      However, even in vitro silaffin-based peptides alone, with and without
      posttranslational modifications, can efficiently mediate biomimetic silica
      precipitation leading to silica material with different properties as well as
      with encapsulated cargo molecules of a large size range. In this review, the
      biomineralization process of silica in diatoms is summarized with a specific
      focus on silaffins and their in vitro silica precipitation properties.
      Applications in the area of bio- and nanotechnology as well as in diagnostics and
      therapy are discussed. 

PMID- 26295404
TI  - Pregnancy in Women with Systemic Lupus Erythematosus: A Retrospective Study of 83
      Pregnancies at a Single Centre.
AB  - OBJECTIVE: To evaluate the outcome of 80 pregnant women with systemic lupus
      erythematosus (SLE) and explore the risk factors for lupus flare, obstetric
      complications and fetal loss. METHODS: 83 pregnancies in 80 women were divided
      into three groups. Group A: patients in remission for > 6 months before
      pregnancy, proteinuria < 0.5 g per day, without renal failure and discontinuation
      of cytotoxic drugs for > one year; Group B: patients with SLE disease activity in
      the six months before pregnancy; Group C: patients with new onset SLE during
      pregnancy. RESULTS: In group A, 76.47% pregnancies achieved full-term deliveries
      and 80.39% achieved live born infants. In group B and C, the outcome was poor.
      Among 62 patients (64 pregnancies) diagnosed as SLE before pregnancy, SLE flares
      occurred in 27 (42.19%) pregnancies. SLE disease activity in the six months
      before pregnancy was significantly associated with lupus flare (OR 5.00, 95% CI
      1.14-21.87, p = 0.03) and fetal loss. New onset lupus during pregnancy was
      independently associated with obstetric complications (OR 7.22, 95% CI 2.14
      24.38, p = 0.001). CONCLUSIONS: The current study confirmed the previous report
      that SLE should be considered a high risk of pregnancy. If pregnancy is planned
      after remission for > 6 months, the favorable outcome can be achieved.

PMID- 26295407
TI  - The Antiviral Effect of Baicalin on Enterovirus 71 In Vitro.
AB  - Baicalin is a flavonoid compound extracted from Scutellaria roots that has been
      reported to possess antibacterial, anti-inflammatory, and antiviral activities.
      However, the antiviral effect of baicalin on enterovirus 71 (EV71) is still
      unknown. In this study, we found that baicalin showed inhibitory activity on EV71
      infection and was independent of direct virucidal or prophylactic effect and
      inhibitory viral absorption. The expressions of EV71/3D mRNA and polymerase were
      significantly blocked by baicalin treatment at early stages of EV71 infection. In
      addition, baicalin could decrease the expressions of FasL and caspase-3, as well
      as inhibit the apoptosis of EV71-infected human embryonal rhabdomyosarcoma (RD)
      cells. Altogether, these results indicate that baicalin exhibits potent antiviral
      effect on EV71 infection, probably through inhibiting EV71/3D polymerase
      expression and Fas/FasL signaling pathways. 

PMID- 26295408
TI  - Dendritic Cell Protection from Cisplatin Nephrotoxicity Is Independent of
      Neutrophils.
AB  - Cisplatin is a very effective chemotherapeutic agent used against a wide range of
      solid tumors. A major adverse effect of cisplatin therapy is acute kidney injury
      (AKI). Neutrophils are reported to infiltrate and exacerbate injury in a wide
      range of sterile inflammatory models of tissue injury. Here, we studied the
      kinetics of neutrophil infiltration into kidneys and their role in cisplatin
      mediated AKI. Mice treated with cisplatin showed an increase in circulating
      neutrophils 24 and 48 h after cisplatin administration. Cisplatin treatment
      caused an increase in kidney leukocytes with neutrophils accounting for the
      majority of the infiltrating leukocytes. The extent of neutrophil infiltration
      coincided with the severity of kidney injury and renal dysfunction. To examine
      the functional relevance of infiltrating neutrophils in cisplatin nephrotoxicity,
      we depleted neutrophils using a neutrophil-specific antibody (anti-Ly-6G). This
      antibody resulted in greater than 90% depletion of neutrophils in both the blood
      and kidney. Of note, depletion of neutrophils had no impact on the extent of
      cisplatin-induced AKI as compared to non-depleted mice. Earlier, we reported that
      dendritic cell depletion in CD11c-DTRtg mice causes exacerbation of AKI and a
      dramatic increase in renal neutrophils. Thus, we also examined the role of
      neutrophils in dendritic cell-depleted mice treated with cisplatin. Dendritic
      cell depletion exacerbated AKI in spite of neutrophil depletion. These data
      demonstrate that cisplatin nephrotoxicity is not mediated by neutrophils and that
      dendritic cells protect kidneys via neutrophil-independent mechanisms. 

PMID- 26295409
TI  - Extracellular Xylanolytic and Pectinolytic Hydrolase Production by Aspergillus
      flavus Isolates Contributes to Crop Invasion.
AB  - Several atoxigenic Aspergillus flavus isolates, including some being used as
      biocontrol agents, and one toxigenic isolate were surveyed for the ability to
      produce extracellular xylanolytic and pectinolytic hydrolases. All of the tested
      isolates displayed good production of endoxylanases when grown on a medium
      utilizing larch xylan as a sole carbon substrate. Four of the tested isolates
      produced reasonably high levels of esterase activity, while the atoxigenic
      biocontrol agent NRRL 21882 isolate esterase level was significantly lower than
      the others. Atoxigenic A. flavus isolates 19, 22, K49, AF36 (the latter two are
      biocontrol agents) and toxigenic AF13 produced copious levels of pectinolytic
      activity when grown on a pectin medium. The pectinolytic activity levels of the
      atoxigenic A. flavus 17 and NRRL 21882 isolates were significantly lower than the
      other tested isolates. In addition, A. flavus isolates that displayed high levels
      of pectinolytic activity in the plate assay produced high levels of
      endopolygalacturonase (pectinase) P2c, as ascertained by isoelectric focusing
      electrophoresis. Isolate NRRL 21882 displayed low levels of both pectinase P2c
      and pectin methyl esterase. A. flavus appears capable of producing these
      hydrolytic enzymes irrespective of aflatoxin production. This ability of
      atoxigenic isolates to produce xylanolytic and pectinolytic hydrolases mimics
      that of toxigenic isolates and, therefore, contributes to the ability of
      atoxigenic isolates to occupy the same niche as A. flavus toxigenic isolates. 

PMID- 26295405
TI  - Regulation of the Host Antiviral State by Intercellular Communications.
AB  - Viruses usually induce a profound remodeling of host cells, including the
      usurpation of host machinery to support their replication and production of
      virions to invade new cells. Nonetheless, recognition of viruses by the host
      often triggers innate immune signaling, preventing viral spread and modulating
      the function of immune cells. It conventionally occurs through production of
      antiviral factors and cytokines by infected cells. Virtually all viruses have
      evolved mechanisms to blunt such responses. Importantly, it is becoming
      increasingly recognized that infected cells also transmit signals to regulate
      innate immunity in uninfected neighboring cells. These alternative pathways are
      notably mediated by vesicular secretion of various virus- and host-derived
      products (miRNAs, RNAs, and proteins) and non-infectious viral particles. In this
      review, we focus on these newly-described modes of cell-to-cell communications
      and their impact on neighboring cell functions. The reception of these signals
      can have anti- and pro-viral impacts, as well as more complex effects in the host
      such as oncogenesis and inflammation. Therefore, these "broadcasting" functions,
      which might be tuned by an arms race involving selective evolution driven by
      either the host or the virus, constitute novel and original regulations of viral
      infection, either highly localized or systemic. 

PMID- 26295411
TI  - Optimized Production of Xylitol from Xylose Using a Hyper-Acidophilic Candida
      tropicalis.
AB  - The yeast Candida tropicalis DSM 7524 produces xylitol, a natural, low-calorie
      sweetener, by fermentation of xylose. In order to increase xylitol production
      rate during the submerged fermentation process, some parameters-substrate
      (xylose) concentration, pH, aeration rate, temperature and fermentation strategy
      have been optimized. The maximum xylitol yield reached at 60-80 g/L initial
      xylose concentration, pH 5.5 at 37  degrees C was 83.66% (w/w) on consumed xylose
      in microaerophilic conditions (kLa = 2.h(-1)). Scaling up on 3 L fermenter, with
      a fed-batch strategy, the best xylitol yield was 86.84% (w/w), against a 90% of
      theoretical yield. The hyper-acidophilic behaviour of C. tropicalis makes this
      strain particularly promising for industrial application, due to the possibility
      to work in non-sterile conditions. 

PMID- 26295406
TI  - Regulation of the Wnt/beta-Catenin Signaling Pathway by Human Papillomavirus E6
      and E7 Oncoproteins.
AB  - Cell signaling pathways are the mechanisms by which cells transduce external
      stimuli, which control the transcription of genes, to regulate diverse biological
      effects. In cancer, distinct signaling pathways, such as the Wnt/beta-catenin
      pathway, have been implicated in the deregulation of critical molecular processes
      that affect cell proliferation and differentiation. For example, changes in beta
      catenin localization have been identified in Human Papillomavirus (HPV)-related
      cancers as the lesion progresses. Specifically, beta-catenin relocates from the
      membrane/cytoplasm to the nucleus, suggesting that this transcription regulator
      participates in cervical carcinogenesis. The E6 and E7 oncoproteins are
      responsible for the transforming activity of HPV, and some studies have
      implicated these viral oncoproteins in the regulation of the Wnt/beta-catenin
      pathway. Nevertheless, new interactions of HPV oncoproteins with cellular
      proteins are emerging, and the study of the biological effects of such
      interactions will help to understand HPV-related carcinogenesis. Viruses 2015, 7
      4735 This review addresses the accumulated evidence of the involvement of the HPV
      E6 and E7 oncoproteins in the activation of the Wnt/beta-catenin pathway. 

PMID- 26295413
TI  - Strontium biokinetic model for the pregnant woman and fetus: application to Techa
      River studies.
AB  - A biokinetic model for strontium (Sr) for the pregnant woman and fetus (Sr-PWF
      model) has been developed for use in the quantification of doses from internal
      radiation exposures following maternal ingestion of Sr radioisotopes before or
      during pregnancy. The model relates in particular to the population of the Techa
      River villages exposed to significant amounts of ingested Sr radioisotopes as a
      result of releases of liquid radioactive wastes from the Mayak plutonium
      production facility (Russia) in the early 1950s. The biokinetic model for Sr
      metabolism in the pregnant woman was based on a biokinetic model for the adult
      female modified to account for changes in mineral metabolism during pregnancy.
      The model for non-pregnant females of all ages was developed earlier with the use
      of extensive data on (90)Sr-body measurements in the Techa Riverside residents.
      To determine changes in model parameter values to take account of changing
      mineral metabolism during pregnancy, data from longitudinal studies of calcium
      homeostasis during human pregnancy were analysed and applied. Exchanges between
      maternal and fetal circulations and retention in fetal skeleton and soft tissues
      were modelled as adaptations of previously published models, taking account of
      data on Sr and calcium (Ca) metabolism obtained in Russia (Southern Urals and
      Moscow) relating to dietary calcium intakes, calcium contents in maternal and
      fetal skeletons and strontium transfer to the fetus. The model was validated
      using independent data on (90)Sr in the fetal skeleton from global fallout as
      well as unique data on (90)Sr-body burden in mothers and their still-born
      children for Techa River residents. While the Sr-PWF model has been developed
      specifically for ingestion of Sr isotopes by Techa River residents, it is also
      more widely applicable to maternal ingestion of Sr radioisotopes at different
      times before and during pregnancy and different ages of pregnant women in a
      general population. 

PMID- 26295410
TI  - Dichotomy in the Epigenetic Mark Lysine Acetylation is Critical for the
      Proliferation of Prostate Cancer Cells.
AB  - The dynamics of lysine acetylation serve as a major epigenetic mark, which
      regulates cellular response to inflammation, DNA damage and hormonal changes.
      Microarray assays reveal changes in gene expression, but cannot predict
      regulation of a protein function by epigenetic modifications. The present study
      employs computational tools to inclusively analyze microarray data to understand
      the potential role of acetylation during development of androgen-independent PCa.
      The data revealed that the androgen receptor interacts with 333 proteins, out of
      which at least 92 proteins were acetylated. Notably, the number of cellular
      proteins undergoing acetylation in the androgen-dependent PCa was more as
      compared to the androgen-independent PCa. Specifically, the 32 lysine-acetylated
      proteins in the cellular models of androgen-dependent PCa were mainly involved in
      regulating stability as well as pre- and post-processing of mRNA. Collectively,
      the data demonstrate that protein lysine acetylation plays a crucial role during
      the transition of androgen-dependent to -independent PCa, which importantly,
      could also serve as a functional axis to unravel new therapeutic targets. 

PMID- 26295414
TI  - Silicon Oxysulfide, OSiS: Rotational Spectrum, Quantum-Chemical Calculations, and
      Equilibrium Structure.
AB  - Silicon oxysulfide, OSiS, and seven of its minor isotopic species have been
      characterized for the first time in the gas phase at high spectral resolution by
      means of Fourier transform microwave spectroscopy. The equilibrium structure of
      OSiS has been determined from the experimental data using calculated vibration
      rotation interaction constants. The structural parameters (rO-Si = 1.5064 A and
      rSi-S = 1.9133 A) are in very good agreement with values from high-level quantum
      chemical calculations using coupled-cluster techniques together with
      sophisticated additivity and extrapolation schemes. The bond distances in OSiS
      are very short in comparison with those in SiO and SiS. This unexpected finding
      is explained by the partial charges calculated for OSiS via a natural population
      analysis. The results suggest that electrostatic effects rather than multiple
      bonding are the key factors in determining bonding in this triatomic molecule.
      The data presented provide the spectroscopic information needed for radio
      astronomical searches for OSiS. 

PMID- 26295412
TI  - Mn(V)(O) versus Cr(V)(O) Porphyrinoid Complexes: Structural Characterization and
      Implications for Basicity Controlling H-Atom Abstraction.
AB  - Isomorphous crystals of Mn(V)(O) and Cr(V)(O) corrolazines were characterized by
      single crystal X-ray diffraction. Reactivity studies with H atom donors and
      separated PCET reagents show a dramatic difference in H atom abstracting
      abilities for these two complexes. The implied large difference in driving force
      is opposite the trend in redox potentials, indicating that basicity is a key
      factor in determining the striking difference in reactivity for two metal-oxo
      species in identical ligand environments. 

PMID- 26295415
TI  - Why Do Sulfuric Acid Coatings Influence the Ice Nucleation Properties of Mineral
      Dust Particles in the Atmosphere?
AB  - Laboratory studies with supermicrometer particles have shown that mineral
      particles coated with sulfuric acid are relatively poor ice nuclei. We
      investigated this phenomenon, which is of atmospheric relevance, by probing the
      structure of water at the mineral-aqueous acid interface as a function of the
      sulfuric acid concentration using sum frequency generation vibrational
      spectroscopy. We found that ordered water structures at water/mica interfaces
      drastically diminished at molarities of sulfuric acid equal to 0.5 M and totally
      disappeared when the molarities reached 5 M. The decrease in ordered water
      structures at the interface was caused by a combined effect of the decreased mica
      surface potential at low pH, the adsorption of sulfates on mica, and the lack of
      free water molecules in high concentrations of acidic solution. The good ice
      nucleation ability above liquid water saturation is correlated with the presence
      of structured water, suggesting that structured water at the interface may be
      needed for efficient heterogeneous ice nucleation. 

PMID- 26295416
TI  - Role of Geometric Relaxation in Oxygen Binding to Metal Nanoparticles.
AB  - Better oxygen reduction catalysts are needed to improve the efficiency and lower
      the cost of fuel cells. Metal nanoparticles are good candidates because their
      catalytic properties can differ from bulk metals. Using density functional theory
      calculations, we studied the geometric relaxation of metal nanoparticles upon
      oxygen binding. Because bound oxygen species are intermediates in the oxygen
      reduction reaction, the binding of oxygen can be correlated to catalytic
      activity. Our results show that Pt and Au are unique in that they exhibit a
      larger structural deformation than other metals, which is pronounced for
      particles with fewer than 100 atoms. The structural deformation induced by atomic
      oxygen binding stabilizes the oxidized state and thus reduces the catalytic
      activity of Pt-based random alloys. We show that the catalytic activity of Pt can
      be improved by forming alloys with less deformable metals. 

PMID- 26295417
TI  - Spectrally Resolved Photoluminescence Imaging of ZnO Nanocrystals at Single
      Particle Levels.
AB  - The intrinsic spectral line widths of defect-related transitions in quantum
      confined semiconductor nanocrystals are often difficult to estimate using
      ensemble measurements because the extent of inhomogeneous broadening due to
      particle size distributions is not known precisely. To address this problem, we
      performed spectrally resolved photoluminescence (PL) microscopy of individual ZnO
      NC by directly populating the defects states using low-energy laser excitation.
      The temporal evolution of PL intensities shows discrete blinking behaviors,
      suggesting that the NCs are detected near single-particle levels. The transition
      energies of individual NCs are found to fluctuate around their mean position
      (2.25 eV) by ~0.130 eV, which is attributed to particle size distribution and
      defects densities associated with each NC. The spectral line width associated
      with defect emission envelope of ZnO NCs is found to be inherently broad (200-400
      meV), which further establishes the presence of multiple closely spaced defect
      energy levels within every ZnO NC. 

PMID- 26295418
TI  - Simplified Sum-Over-States Approach for Predicting Resonance Raman Spectra.
      Application to Nucleic Acid Bases.
AB  - Resonance Raman spectra provide a valuable probe into molecular excited-state
      structures and properties. Moreover, resonance enhancement is of importance for
      the chemical contribution to surface-enhanced Raman scattering. In this work, we
      introduce a simplified sum-over-states scheme for computing Raman spectra and
      Raman excitation profiles. The proposed sum-over-states approach uses derivatives
      of electronic excitation energies and transition dipole moments, which can be
      efficiently computed from time-dependent density functional theory. We analyze
      and interpret the resonance Raman spectra and Raman excitation profiles of
      nucleic acid bases using the present approach. Contributions of individual
      excited states under strictly resonant and nonresonant conditions are
      investigated, and smooth interpolation between both limiting cases is obtained. 

PMID- 26295419
TI  - Computational Modeling of Stark Effects in Organic Dye-Sensitized TiO2
      Heterointerfaces.
AB  - We report a computational modeling study, based on DFT and time-dependent DFT
      techniques, to investigate the origin and the effect of local electric fields on
      the optical properties of organic dye-sensitized heterointerfaces, examining the
      case of the indoline D149 sensitizer on TiO2. On the one hand, we give precise
      information about the anchoring mode of D149 and its orientation with respect to
      the TiO2 surface, and on the other hand, we provide the computational framework
      model to interpret the Stark shifts experimentally observed by PIA spectroscopy.
      Our results show that the presence of oxidized dye molecules induces major
      spectral changes on the adjacent neutral dyes, which, along with the simulated
      effect of injected charge into TiO2, provide Stark shifts nicely reproducing the
      experimental observations. 

PMID- 26295420
TI  - Advances in Phosphors for Light-emitting Diodes.
AB  - Light-emitting diodes (LEDs) are excellent candidates for general lighting
      because of their rapidly improving efficiency, durability, and reliability, their
      usability in products of various sizes, and their environmentally friendly
      constituents. Effective lighting devices can be realized by combining one or more
      phosphor materials with chips. Accordingly, it is very important that the
      architecture of phosphors be developed. Although numerous phosphors have been
      proposed in the past several years, the range of phosphors that are suitable for
      LEDs is limited. This work describes recent progress in our understanding of the
      prescription, morphology, structure, spectrum, and packaging of such phosphors.
      It suggests avenues for further development and the scientific challenges that
      must be overcome before phosphors can be practically applied in LEDs. 

PMID- 26295421
TI  - Synergistic Formation of Radicals by Irradiation with Both Vacuum Ultraviolet and
      Atomic Hydrogen: A Real-Time In Situ Electron Spin Resonance Study.
AB  - We report on the surface modification of poly(tetrafluoroethylene) (PTFE) as an
      example of soft materials and biomaterials that occur under plasma discharge by
      kinetics analysis of radical formation using in situ real-time electron spin
      resonance (ESR) measurements. During irradiation with hydrogen plasma,
      simultaneous measurements of the gas-phase ESR signals of atomic hydrogen and the
      carbon dangling bond (C-DB) on PTFE were performed. Dynamic changes of the C-DB
      density were observed in real time, where the rate of density change was
      accelerated during initial irradiation and then became constant over time. It is
      noteworthy that C-DBs were formed synergistically by irradiation with both vacuum
      ultraviolet (VUV) and atomic hydrogen. The in situ real-time ESR technique is
      useful to elucidate synergistic roles during plasma surface modification. 

PMID- 26295422
TI  - Multiple Exciton Generation in Semiconductor Quantum Dots.
AB  - Multiple exciton generation in quantum dots (QDs) has been intensively studied as
      a way to enhance solar energy conversion by utilizing the excess energy in the
      absorbed photons. Among other useful properties, quantum confinement can both
      increase Coulomb interactions that drive the MEG process and decrease the
      electron-phonon coupling that cools hot excitons in bulk semiconductors. However,
      variations in the reported enhanced quantum yields (QYs) have led to
      disagreements over the role that quantum confinement plays. The enhanced yield of
      excitons per absorbed photon is deduced from a dynamical signature in the
      transient absorption or transient photoluminescence and is ascribed to the
      creation of biexcitons. Extraneous effects such as photocharging are partially
      responsible for the observed variations. When these extraneous effects are
      reduced, the MEG efficiency, defined in terms of the number of additional
      electron-hole pairs produced per additional band gap of photon excitation, is
      about two times better in PbSe QDs than that in bulk PbSe. Thin films of
      electronically coupled QDs have shown promise in simple photon-to-electron
      conversion architectures. If the MEG efficiency can be further enhanced and
      charge separation and transport can be optimized within QD films, then QD solar
      cells can lead to third-generation solar energy conversion technologies. 

PMID- 26295423
TI  - Optimal (2)H rf Pulses and (2)H-(13)C Cross-Polarization Methods for Solid-State
      (2)H MAS NMR of Perdeuterated Proteins.
AB  - We present a novel concept for rf pulses and optimal control designed cross
      polarization experiments for quadrupolar nuclei. The methods are demonstrated for
      (2)H CP-MAS and (2)H multiple-pulse NMR of perdeuterated proteins, for which
      sensitivity enhancements up to an order of magnitude are presented relative to
      commonly used approaches. The so-called RESPIRATION rf pulses combines the
      concept of short broad-band pulses with generation of pulses with large flip
      angles through distribution of the rf pulse over several rotor echoes. This lead
      to close-to-ideal rf pulses, facilitating implementation of experiments relying
      on the ability to realize high-performance 90 and 180 degrees  pulses, as, for
      example, in refocused INEPT and double-to-single quantum coherence experiments,
      or just pulses that provide a true representation of the quadrupolar powder
      pattern to extract information about the structure or dynamics. The optimal
      control (2)H -> (13)C CP-MAS method demonstrates transfer efficiencies up to
      around 85% while being extremely robust toward rf inhomogeneity and resonance
      offsets. 

PMID- 26295424
TI  - Formation of Secondary Organic Aerosol from the Direct Photolytic Generation of
      Organic Radicals.
AB  - The immense complexity inherent in the formation of secondary organic aerosol
      (SOA)-due primarily to the large number of oxidation steps and reaction pathways
      involved-has limited the detailed understanding of its underlying chemistry. As a
      means of simplifying such complexity, here we demonstrate the formation of SOA
      through the photolysis of gas-phase alkyl iodides, which generates organic peroxy
      radicals of known structure. In contrast to standard OH-initiated oxidation
      experiments, photolytically initiated oxidation forms a limited number of
      products via a single reactive step. As is typical for SOA, the yields of aerosol
      generated from the photolysis of alkyl iodides depend on aerosol loading,
      indicating the semivolatile nature of the particulate species. However, the
      aerosol was observed to be higher in volatility and less oxidized than in
      previous multigenerational studies of alkane oxidation, suggesting that
      additional oxidative steps are necessary to produce oxidized semivolatile
      material in the atmosphere. Despite the relative simplicity of this chemical
      system, the SOA mass spectra are still quite complex, underscoring the wide range
      of products present in SOA. 

PMID- 26295425
TI  - Solar Energy Conversion and Environmental Remediation Using Inorganic
      Semiconductor-Liquid Interfaces: The Road Traveled and the Way Forward.
AB  - Unlike their solid-state counterparts, semiconductor-liquid junctions are
      versatile in that the incident solar energy can be stored in the form of chemical
      fuels. Another attractive application is the use of irradiated oxide
      semiconductor-coated surfaces for self-cleaning and antifogging. The theme of
      this history-tinged Guest Commentary centers on the question of what has been
      accomplished in the above "photoelectrochemical" schemes over the 35 year time
      frame from 1975 to 2010. Progress in this field was aided by the infusion of new
      concepts and contributions from the materials chemistry and physics communities.
      A related aspect of discussion is how the active semiconductor material has
      evolved both chemically and morphologically in these applications. It is shown
      that despite impressive research advances, only a handful of the above concepts
      (e.g., dye-sensitized solar photon conversion and self-cleaning and antifogging
      surfaces) have made the successful transition from the laboratory to the
      marketplace. 

PMID- 26295426
TI  - Stability and Properties of Two-Dimensional Graphene Hydroxide.
AB  - Systematic study of interaction between graphene and hydroxyls is carried out by
      first-principles calculations. Although single hydroxyl adsorbed on graphene
      presents magnetic properties, hydroxyls prefer to adsorb on graphene in pairs
      without magnetic properties. The formation energy of hydroxyl pairs with graphene
      is coverage-dependent, and the most stable structure is half-covered by hydroxyl
      pairs along zigzag chains with alternative sp2 and sp3 hybridization between
      carbon atoms. The bandgap of this structure is 0.97 eV in GW approximation, close
      to the bandgap of Si, and this structure is stable at room temperature. It is
      possible to build graphene-based electronic circuits from graphene hydroxide
      without the need for cutting or etching. 

PMID- 26295427
TI  - Optical Properties and Charge-Transfer Excitations in Edge-Functionalized All
      Graphene Nanojunctions.
AB  - We investigate the optical properties of edge-functionalized graphene
      nanosystems, focusing on the formation of junctions and charge-transfer excitons.
      We consider a class of graphene structures that combine the main electronic
      features of graphene with the wide tunability of large polycyclic aromatic
      hydrocarbons. By investigating prototypical ribbon-like systems, we show that,
      upon convenient choice of functional groups, low-energy excitations with
      remarkable charge-transfer character and large oscillator strength are obtained.
      These properties can be further modulated through an appropriate width variation,
      thus spanning a wide range in the low-energy region of the UV-vis spectra. Our
      results are relevant in view of designing all-graphene optoelectronic
      nanodevices, which take advantage of the versatility of molecular
      functionalization, together with the stability and the electronic properties of
      graphene nanostructures. 

PMID- 26295428
TI  - Atomistic Characterization of Stochastic Cavitation of a Binary Metallic Liquid
      under Negative Pressure.
AB  - We demonstrate the stochastic nature of cavitation in a binary metallic liquid
      Cu46Zr54 during hydrostatic expansion by employing molecular dynamics (MD)
      simulations using a quantum mechanics (QM)-derived potential. The activation
      volume is obtained from MD simulations and transition-state theory. Extrapolation
      of the pressure dependence of the activation volume from our MD simulations to
      low tensile pressure agrees remarkably with macroscale cavitation experiments. We
      find that classical nucleation theory can predict the cavitation rate if we
      incorporate the Tolman length derived from the MD simulations. 

PMID- 26295429
TI  - Evanescent-Wave Cavity Ring-Down Ellipsometry.
AB  - We introduce the new technique of evanescent-wave cavity ring-down ellipsometry
      (EW-CRDE), used for the measurement of ellipsometric angles of samples at a solid
      gas or solid-liquid interface, and achieve phase-shift measurements with
      precision of ~0.01 degrees . We demonstrate the technique by measuring the time
      dependent refractive index of methanol-water mixtures and thin films at the
      liquid/fused-silica interface, showing that the monitoring of monolayers on
      microsecond time scales using EW-CRDE should be achievable. 

PMID- 26295430
TI  - Catalytic Activity of Pd/Cu Random Alloy Nanoparticles for Oxygen Reduction.
AB  - Trends in oxygen reduction activity of Pd/Cu bimetallic random alloy
      nanoparticles are determined with calculations of oxygen binding for a range of
      compositions. A reduction in the average oxygen binding is found as Cu is added
      to Pd, indicating an increase in catalytic activity up to a peak at 1:1 Pd/Cu
      ratio. Calculations show that Cu reduces the Pd-O binding energy and Pd increases
      the Cu-O binding energy. These changes are understood in terms of charge transfer
      from Pd to Cu, lowering the d-band center of Pd and raising that of Cu. The peak
      in activity occurs because these two effects not equivalent. A greater overlap
      between the d-states of Pd and the adsorbed oxygen makes the reduction in binding
      at Pd more significant than the increase in binding at Cu. We present a simple
      model of the average binding energy that can generally predict activity trends in
      random alloys. 

PMID- 26295431
TI  - Pt-Covered Multiwall Carbon Nanotubes for Oxygen Reduction in Fuel Cell
      Applications.
AB  - Recently one-dimensonal (1-D) Pt nanostructures have shown greatly enhanced
      intrinsic oxygen reduction reaction (ORR) activity (ORR kinetic current
      normalized to Pt surface area) and/or improved durability relative to
      conventional supported Pt catalysts. In this study, we report a simple synthetic
      route to create Pt-covered multiwall carbon nanotubes (Pt NPs/MWNTs) as promising
      1-D Pt nanostructured catalysts for ORR in proton exchange membrane fuel cells
      (PEMFCs). The average ORR intrinsic activity of Pt NPs/MWNTs is ~0.95 mA/cm(2) Pt
      at 0.9 ViR-corrected versus reversible hydrogen electrode (RHE), ~3-fold higher
      than a commercial catalyst -46 wt % Pt/C (Tanaka Kikinzoku Kogyo) in 0.1 M HClO4
      at room temperature. More significantly, the mass activity of Pt NPs/MWNTs
      measured (~0.48 A/mgPt at 0.9 ViR-corrected vs RHE) is higher than other 1-D
      nanostructured catalysts and TKK catalysts. The enhanced intrinsic activity of 1
      D Pt NPs/MWNTs could be attributed to the weak chemical adsorption energy of
      OHads-species on the surface Pt NPs covering MWNTs. 

PMID- 26295432
TI  - Selective Interlayers and Contacts in Organic Photovoltaic Cells.
AB  - Organic photovoltaic cells (OPVs) are promising solar electric energy conversion
      systems with impressive recent optimization of active layers. OPV optimization
      must now be accompanied by the development of new charge-selective contacts and
      interlayers. This Perspective considers the role of interface science in energy
      harvesting using OPVs, looking back at early photoelectrochemical (photogalvanic)
      energy conversion platforms, which suffered from a lack of charge carrier
      selectivity. We then examine recent platforms and the fundamental aspects of
      selective harvesting of holes and electrons at opposite contacts. For blended
      heterojunction OPVs, contact/interlayer design is especially critical because
      charge harvesting competes with recombination at these same contacts. New
      interlayer materials can modify contacts to both control work function and
      introduce selectivity and chemical compatibility with nonpolar active layers and
      add thermodynamic and kinetic selectivity to charge harvesting. We briefly
      discuss the surface and interface science required for the development of new
      interlayer materials and take a look ahead at the challenges yet to be faced in
      their optimization. 

PMID- 26295433
TI  - Challenges and Opportunities in Light and Electrical Energy Conversion.

PMID- 26295434
TI  - A novel Trojan-horse targeting strategy to reduce the non-specific uptake of
      nanocarriers by non-cancerous cells.
AB  - One big challenge with active targeting of nanocarriers is non-specific binding
      between targeting molecules and non-target moieties expressed on non-cancerous
      cells, which leads to non-specific uptake of nanocarriers by non-cancerous cells.
      Here, we propose a novel Trojan-horse targeting strategy to hide or expose the
      targeting molecules of nanocarriers on-demand. The non-specific uptake by non
      cancerous cells can be reduced because the targeting molecules are hidden in
      hydrophilic polymers. The nanocarriers are still actively targetable to cancer
      cells because the targeting molecules can be exposed on-demand at tumor regions.
      Typically, Fe3O4 nanocrystals (FN) as magnetic resonance imaging (MRI) contrast
      agents were encapsulated into albumin nanoparticles (AN), and then folic acid
      (FA) and pH-sensitive polymers (PP) were grafted onto the surface of AN-FN to
      construct PP-FA-AN-FN nanoparticles. Fourier transform infrared spectroscopy (FT
      IR), dynamic light scattering (DLS), transmission electron microscope (TEM) and
      gel permeation chromatography (GPC) results confirm successful construction of PP
      FA-AN-FN. According to difference of nanoparticle-cellular uptake between pH 7.4
      and 5.5, the weight ratio of conjugated PP to nanoparticle FA-AN-FN (i.e. graft
      density) and the molecular weight of PP (i.e. graft length) are optimized to be
      1.32 and 5.7 kDa, respectively. In vitro studies confirm that the PP can hide
      ligand FA to prevent it from binding to cells with FRalpha at pH 7.4 and shrink
      to expose FA at pH 5.5. In vivo studies demonstrate that our Trojan-horse
      targeting strategy can reduce the non-specific uptake of the PP-FA-AN-FN by non
      cancerous cells. Therefore, our PP-FA-AN-FN might be used as an accurately
      targeted MRI contrast agent. 

PMID- 26295435
TI  - Silver nanoparticle-induced hemoglobin decrease involves alteration of histone 3
      methylation status.
AB  - Silver nanoparticles (nanosilver, AgNPs) have been shown to induce toxicity in
      vitro and in vivo; however, the molecular bases underlying the detrimental
      effects have not been thoroughly understood. Although there are numerous studies
      on its genotoxicity, only a few studies have investigated the epigenetic changes,
      even less on the changes of histone modifications by AgNPs. In the current study,
      we probed the AgNP-induced alterations to histone methylation that could be
      responsible for globin reduction in erythroid cells. AgNP treatment caused a
      significant reduction of global methylation level for histone 3 (H3) in erythroid
      MEL cells at sublethal concentrations, devoid of oxidative stress. The ChIP-PCR
      analyses demonstrated that methylation of H3 at lysine (Lys) 4 (H3K4) and Lys 79
      (H3K79) on the beta-globin locus was greatly reduced. The reduction in
      methylation could be attributed to decreased histone methyltransferase DOT-1L and
      MLL levels as well as the direct binding between AgNPs to H3/H4 that provide
      steric hindrance to prevent methylation as predicted by the all-atom molecular
      dynamics simulations. This direct interaction was further proved by AgNP-mediated
      pull-down assay and immunoprecipitation assay. These changes, together with
      decreased RNA polymerase II activity and chromatin binding at this locus,
      resulted in decreased hemoglobin production. By contrast, Ag ion-treated cells
      showed no alterations in histone methylation level. Taken together, these results
      showed a novel finding in which AgNPs could alter the methylation status of
      histone. Our study therefore opens a new avenue to study the biological effects
      of AgNPs at sublethal concentrations from the perspective of epigenetic
      mechanisms. 

PMID- 26295437
TI  - Reductions in mortality among Medicare beneficiaries following the implementation
      of Medicare Part D.
AB  - Medicare Part D is a prescription drug program that provides seniors and disabled
      individuals enrolled in Medicare with outpatient drug coverage benefits. Part D
      has been shown to increase access to medicines and improve medication adherence;
      however, the effect of Part D on health outcomes has not yet been extensively
      studied. In this study, we used a published and validated Markov-based
      microsimulation model to quantify the relationships among medication use, disease
      incidence and severity, and mortality. Based on the simulation results, we
      estimate that since the implementation of Part D in 2006, nearly 200,000 Medicare
      beneficiaries have lived at least 1 year longer. Reductions in mortality have
      occurred because of fewer deaths associated with medication-sensitive conditions
      such as diabetes, congestive heart failure, stroke, and myocardial infarction.
      Improved access to medication through Medicare Part D helps patients improve
      blood pressure, cholesterol, and blood glucose levels, which in turn can prevent
      or delay the onset of disease and the incidence of adverse health events, thus
      reducing mortality. 

PMID- 26295436
TI  - Nutrient-deprived cancer cells preferentially use sialic acid to maintain cell
      surface glycosylation.
AB  - Cancer is characterized by abnormal energy metabolism shaped by nutrient
      deprivation that malignant cells experience during various stages of tumor
      development. This study investigated the response of nutrient-deprived cancer
      cells and their non-malignant counterparts to sialic acid supplementation and
      found that cells utilize negligible amounts of this sugar for energy. Instead
      cells use sialic acid to maintain cell surface glycosylation through
      complementary mechanisms. First, levels of key metabolites (e.g., UDP-GlcNAc and
      CMP-Neu5Ac) required for glycan biosynthesis are maintained or enhanced upon
      Neu5Ac supplementation. In concert, sialyltransferase expression increased at
      both the mRNA and protein levels, which facilitated increased sialylation in
      biochemical assays that measure sialyltransferase activity as well as at the
      whole cell level. In the course of these experiments, several important
      differences emerged that differentiated the cancer cells from their normal
      counterparts including resistant to sialic acid-mediated energy depletion,
      consistently more robust sialic acid-mediated glycan display, and distinctive
      cell surface vs. internal vesicle display of newly-produced sialoglycans.
      Finally, the impact of sialic acid supplementation on specific markers implicated
      in cancer progression was demonstrated by measuring levels of expression and
      sialylation of EGFR1 and MUC1 as well as the corresponding function of sialic
      acid-supplemented cells in migration assays. These findings both provide
      fundamental insight into the biological basis of sialic acid supplementation of
      nutrient-deprived cancer cells and open the door to the development of diagnostic
      and prognostic tools. 

PMID- 26295438
TI  - Improving distillation method and device of tritiated water analysis for ultra
      high decontamination efficiency.
AB  - It is important that monitoring environmental tritiated water for understanding
      the contamination dispersion of the nuclear facilities. Tritium is a pure beta
      radionuclide which is usually measured by Liquid Scintillation Counting (LSC).
      The average energy of tritum beta is only 5.658 keV that makes the LSC counting
      of tritium easily be interfered by the beta emitted by other radionuclides.
      Environmental tritiated water samples usually need to be decontaminated by
      distillation for reducing the interference. After Fukushima Nucleaer Accident,
      the highest gross beta concentration of groundwater samples obtained around
      Fukushima Daiichi Nuclear Power Station is over 1,000,000 Bq/l. There is a need
      for a distillation with ultra-high decontamination efficiency for environmental
      tritiated water analysis. This study is intended to improve the heating
      temperature control for better sub-boiling distillation control and modify the
      height of the container of the air cooling distillation device for better
      fractional distillation effect. The DF of Cs-137 of the distillation may reach
      450,000 which is far better than the prior study. The average loss rate of the
      improved method and device is about 2.6% which is better than the bias value
      listed in the ASTM D4107-08. It is proven that the modified air cooling
      distillation device can provide an easy-handling, water-saving, low cost and
      effective way of purifying water samples for higher beta radionuclides
      contaminated water samples which need ultra-high decontamination treatment. 

PMID- 26295440
TI  - Application of laboratory prepared and commercially available biochars to
      adsorption of cadmium, copper and zinc ions from water.
AB  - The goal of the presented work was the evaluation and comparison of two biochars
      (produced from Sida hermaphrodita - BCSH/laboratory produced and from wheatstraw 
      BCS/commercial available) to adsorb heavy metal ions (Cd(II), Cu(II) and Zn(II))
      from water. Kinetics of the sorption as well as sorption isotherms, the influence
      of solution pH and interfering ions were investigated. Different physico-chemical
      properties of biochars had the great influence on adsorption capacity. The
      greater adsorption efficiency was observed for BCSH than for BCS in the case of
      all investigated metals. The adsorption efficiency of BCSH was correlated with
      higher content of carbon and oxygen, what is equal with higher content of polar
      groups on the BCSH surface e.g., -COOH. Furthermore, the molar ratio of O/C as
      well as polarity index (which was higher for BCSH) was also important parameters.

PMID- 26295442
TI  - A novel method for the synthesis of symmetrical triacylglycerols by enzymatic
      transesterification.
AB  - A novel two-step enzymatic method is described in this study to synthesize
      symmetrical triacylglycerols (TAGs) with arachidonic acid (ARA) at the sn-2
      position. The processes included the synthesis of 2-monoacylglycerols (2-MAGs)
      rich in 2-arachidonoylglycerol (2-AG) by enzymatic ethanolysis and the synthesis
      of symmetrical TAGs by enzymatic transesterification between 2-MAGs and vinyl
      palmitate. Under the optimal conditions, desired symmetrical TAGs were obtained
      at 89% yield. In this study, vinyl palmitate rather than palmitic acid was used
      as a novel acyl donor to react with 2-MAGs. It was the first study reporting the
      synthesis of symmetrical TAGs by enzymatic transesterification. The reaction
      using fatty acid vinyl ester as acyl donor is irreversible and temperature is
      low. Low-temperature reaction greatly suppressed the acyl migration of 2-MAGs and
      the irreversible reaction is much more effective compared to reversible reactions
      using free fatty acid and fatty acid ester as acyl donors.

PMID- 26295441
TI  - Cell adhesion, ammonia removal and granulation of autotrophic nitrifying sludge
      facilitated by N-acyl-homoserine lactones.
AB  - In this study, six N-acyl-homoserine lactone (AHL) molecules (C6-HSL, C8-HSL, C10
      HSL, 3-oxo-C6-HSL, 3-oxo-C8-HSL and 3-oxo-C10-HSL) were each dosed into a
      bioreactor and seeded using autotrophic nitrifying sludge (ANS). The effects of
      the AHLs on cell adhesion, nitrification and sludge granulation were
      investigated. The results indicated that the efficiencies of cell adhesion and
      ammonia removal both had a close correlation with the side chain length and beta
      position substituent group of the AHLs. The best-performing AHL in terms of
      accelerating bacterial attached-growth was 3-oxo-C6-HSL, whereas C6-HSL
      outperformed the others in terms of the ammonia degradation rate. The addition of
      3-oxo-C6-HSL or C6-HSL increased the biomass growth rate, microbial activity,
      extracellular proteins and nitrifying bacteria, which can accelerate the
      formation of nitrifying granules. Consequently, selecting AHL molecules that
      could improve bacteria in attached-growth mode and nitrification efficiency
      simultaneously will most likely facilitate the rapid granulation of nitrifying
      sludge.

PMID- 26295443
TI  - An integrated prediction and optimization model of biogas production system at a
      wastewater treatment facility.
AB  - This study proposes an integrated prediction and optimization model by using
      multi-layer perceptron neural network and particle swarm optimization techniques.
      Three different objective functions are formulated. The first one is the
      maximization of methane percentage with single output. The second one is the
      maximization of biogas production with single output. The last one is the
      maximization of biogas quality and biogas production with two outputs. Methane
      percentage, carbon dioxide percentage, and other contents' percentage are used as
      the biogas quality criteria. Based on the formulated models and data from a
      wastewater treatment facility, optimal values of input variables and their
      corresponding maximum output values are found out for each model. It is expected
      that the application of the integrated prediction and optimization models
      increases the biogas production and biogas quality, and contributes to the
      quantity of electricity production at the wastewater treatment facility.

PMID- 26295439
TI  - The Matchmaker Exchange: a platform for rare disease gene discovery.
AB  - There are few better examples of the need for data sharing than in the rare
      disease community, where patients, physicians, and researchers must search for
      "the needle in a haystack" to uncover rare, novel causes of disease within the
      genome. Impeding the pace of discovery has been the existence of many small
      siloed datasets within individual research or clinical laboratory databases
      and/or disease-specific organizations, hoping for serendipitous occasions when
      two distant investigators happen to learn they have a rare phenotype in common
      and can "match" these cases to build evidence for causality. However, serendipity
      has never proven to be a reliable or scalable approach in science. As such, the
      Matchmaker Exchange (MME) was launched to provide a robust and systematic
      approach to rare disease gene discovery through the creation of a federated
      network connecting databases of genotypes and rare phenotypes using a common
      application programming interface (API). The core building blocks of the MME have
      been defined and assembled. Three MME services have now been connected through
      the API and are available for community use. Additional databases that support
      internal matching are anticipated to join the MME network as it continues to
      grow. 

PMID- 26295444
TI  - Studies of adaptive response and mutation induction in MCF-10A cells following
      exposure to chronic or acute ionizing radiation.
AB  - A phenomenon in which exposure to a low adapting dose of radiation makes cells
      more resistant to the effects of a subsequent high dose exposure is termed radio
      adaptive response. Adaptive response could hypothetically reduce the risk of late
      adverse effects of chronic or acute radiation exposures in humans. Understanding
      the underlying mechanisms of such responses is of relevance for radiation
      protection as well as for the clinical applications of radiation in medicine.
      However, due to the variability of responses depending on the model system and
      radiation condition, there is a need to further study under what conditions
      adaptive response can be induced. In this study, we analyzed if there is a dose
      rate dependence for the adapting dose, assuming that the adapting dose induces
      DNA response/repair pathways that are dose rate dependent. MCF-10A cells were
      exposed to a 50mGy adapting dose administered acutely (0.40Gy/min) or chronically
      (1.4mGy/h or 4.1mGy/h) and then irradiated by high acute challenging doses. The
      endpoints of study include clonogenic cell survival and mutation frequency at X
      linked hprt locus. In another series of experiment, cells were exposed to 100mGy
      and 1Gy at different dose rates (acutely and chronically) and then the mutation
      frequencies were studied. Adaptive response was absent at the level of clonogenic
      survival. The mutation frequencies were significantly decreased in the cells pre
      exposed to 50mGy at 1.4mGy/h followed by 1Gy acute exposure as challenging dose.
      Importantly, at single dose exposures (1 Gy or 100mGy), no differences at the
      level of mutation were found comparing different dose rates. 

PMID- 26295446
TI  - And the nasty ones lose in the end: foliar pathogenicity trades off with asexual
      transmission in the Irish famine pathogen Phytophthora infestans.
AB  - A trade-off between pathogenicity and transmission is often postulated to explain
      the persistence of pathogens over time. If demonstrated, it would help to predict
      the evolution of pathogenicity across cropping seasons, and to develop
      sustainable control strategies from this prediction. Unfortunately, experimental
      demonstration of such trade-offs in agricultural plant pathogens remains elusive.
      We measured asexual transmission of Phytophthora infestans isolates differing in
      pathogenicity in two sets of artificial infection experiments under controlled,
      semi-outdoor conditions. Higher foliar pathogenicity decreased mean daughter
      tuber weight, increased infection severity in daughter tubers, and increased stem
      mortality before emergence. The most pathogenic isolates thus suffer a double
      penalty for asexual transmission: a lower survival probability within small and
      severely infected tubers; and a lower infection probability of neighbouring
      healthy plants due to fewer infected stems produced by surviving tubers. Moderate
      tuber resistance favoured transmission of the least pathogenic isolates, while
      high levels of resistance almost abolished transmission of all isolates. These
      data demonstrate a trade-off between foliar pathogenicity and asexual
      transmission over seasons in P. infestans, which should stabilise pathogenicity
      over time in the potato late blight pathosystem and possibly favour clone
      replacement by less pathogenic lineages after demographic bottlenecks. 

PMID- 26295445
TI  - Mechanism of microglia neuroprotection: Involvement of P2X7, TNFalpha, and
      valproic acid.
AB  - Recently, we have demonstrated that ramified microglia are neuroprotective in N
      methyl-D-aspartate (NMDA)-induced excitotoxicity in organotypic hippocampal slice
      cultures (OHSCs). The present study aimed to elucidate the underlying neuron-glia
      communication mechanism. It is shown here that pretreatment of OHSC with high
      concentrations of adenosine 5'-triphosphate (ATP) reduced NMDA-induced neuronal
      death only in presence of microglia. Specific agonists and antagonists identified
      the P2X7 receptor as neuroprotective receptor which was confirmed by absence of
      ATP-dependent neuroprotection in P2X7-deficient OHSC. Microglia replenished
      chimeric OHSC consisting of wild-type tissue replenished with P2X7-deficient
      microglia confirmed the involvement of microglial P2X7 receptor in
      neuroprotection. Stimulation of P2X7 in primary microglia induced tumor necrosis
      factor alpha (TNFalpha) release and blocking TNFalpha by a neutralizing antibody
      in OHSC abolished neuroprotection by ATP. OHSC from TNFalpha-deficient mice show
      increased exicitoxicity and activation of P2X7 did not rescue neuronal survival
      in the absence of TNFalpha. The neuroprotective effect of valproic acid (VPA) was
      strictly dependent on the presence of microglia and was mediated by upregulation
      of P2X7 in the cells. The present study demonstrates that microglia-mediated
      neuroprotection depends on ATP-activated purine receptor P2X7 and induction of
      TNFalpha release. This neuroprotective pathway was strengthened by VPA
      elucidating a novel mechanism for the neuroprotective function of VPA.

PMID- 26295447
TI  - Childhood trauma in patients with self-reported stress-precipitated seizures.
AB  - OBJECTIVE: Stress is the most commonly reported precipitant of epileptic
      seizures, but the mechanism by which stress precipitates seizures and the risk
      factors for stress as a seizure precipitant are poorly understood. Previously, we
      observed higher levels of anxiety symptoms in patients with epilepsy who reported
      stress as a seizure precipitant. Given that childhood trauma increases the risk
      of general psychiatric symptom burden, including anxiety symptoms, we sought to
      examine the relationship between childhood adversity and stress as a seizure
      precipitant. METHODS: Sequential outpatients (N=236) evaluated at the Epilepsy
      Center of the University of Cincinnati Neuroscience Institute who had previously
      enrolled in an earlier study of stress and seizures were enrolled. Subjects
      either endorsed stress as a seizure precipitant [Stress (+)] or not [Stress (-)].
      The Childhood Trauma Questionnaire Short Form (CTQ-SF), a 28-question scale that
      evaluates 5 domains of childhood adversity (physical abuse, physical neglect,
      emotional abuse, emotional neglect, and sexual abuse) was sent via mail and
      returned on paper or electronically from participants. Total CTQ-SF score and CTQ
      SF domain scores were compared between Stress (+) and Stress (-) groups using
      Wilcoxon rank sum test. Spearman's rank correlation between CTQ-SF scores with
      depression and anxiety was also determined, and these analyses were followed by a
      multivariate analysis to identify the association of childhood trauma with other
      factors including anxiety and depression. RESULTS: A total of 119 out of 236 CTQ
      SFs that were sent out were completed. Response rates were 91/195 for Stress (+)
      and 28/41 for Stress (-). The Stress (+) group reported higher scores in
      emotional abuse compared with the Stress (-) group (p=0.029); CTQ-SF total scores
      were higher in the Stress (+) group compared with the Stress (-) group (p=0.08),
      and sexual abuse scores were higher in Stress (+) group (p=0.07), but there were
      no statistically significant differences for other types of trauma. Depression
      and anxiety scores were higher in the Stress (+) group, but anxiety was the only
      independent factor associated with the Stress (+) group in the multivariate
      analysis (p=0.0021). CONCLUSION: Patients with epilepsy who report stress as a
      seizure precipitant are more likely to endorse a history of childhood traumatic
      experiences, particularly emotional abuse, compared with those who do not
      perceive stress as a precipitant. Further study is needed to identify how
      childhood trauma interacts with anxiety in modulating stress response in patients
      with epilepsy.

PMID- 26295448
TI  - Cessation of gamma activity in the dorsomedial nucleus associated with loss of
      consciousness during focal seizures.
AB  - RATIONALE: Impaired consciousness during seizures may be mediated by ictal
      propagation to the thalamus. Functions of individual thalamic nuclei with respect
      to consciousness, however, are largely unknown. The dorsomedial (DM) nucleus of
      the thalamus likely plays a role in arousal and cognition. We propose that
      alterations of firing patterns within the DM nucleus contribute to impaired
      arousal during focal seizures. METHODS: Electroencephalograph data were collected
      from electrodes within the left DM thalamus and midcingulate cortex (MCC) in a
      patient undergoing seizure monitoring. Spectral power was computed across ictal
      states (preictal, ictal, and postictal) and level of consciousness (stupor/sleep
      vs. awake) in the DM nucleus and MCC. RESULTS: Eighty-seven seizures of
      multifocal left frontal and temporal onsets were analyzed, characterized by loss
      of consciousness. At baseline, the left DM nucleus demonstrated rhythmic bursts
      of gamma activity, most frequently and with greatest amplitude during
      wakefulness. This activity ceased as ictal discharges spread to the MCC, and
      consciousness was impaired, and it recurred at the end of each seizure as
      awareness was regained. The analysis of gamma (30-40Hz) power demonstrated that
      when seizures occurred during wakefulness, there was lower DM ictal power
      (p<0.0001) and higher DM postictal power (p<0.0001) relative to the preictal
      epoch. This spectral pattern was not evident within the MCC or when seizures
      occurred during sleep. CONCLUSIONS: Data revealed a characteristic pattern of DM
      gamma bursts during wakefulness, which disappeared during partial seizures
      associated with impaired consciousness. The findings are consistent with studies
      suggesting that the DM nucleus participates in cognition and arousal.

PMID- 26295449
TI  - Local-aggregate modeling for big data via distributed optimization: Applications
      to neuroimaging.
AB  - Technological advances have led to a proliferation of structured big data that
      have matrix-valued covariates. We are specifically motivated to build predictive
      models for multi-subject neuroimaging data based on each subject's brain imaging
      scans. This is an ultra-high-dimensional problem that consists of a matrix of
      covariates (brain locations by time points) for each subject; few methods
      currently exist to fit supervised models directly to this tensor data. We propose
      a novel modeling and algorithmic strategy to apply generalized linear models
      (GLMs) to this massive tensor data in which one set of variables is associated
      with locations. Our method begins by fitting GLMs to each location separately,
      and then builds an ensemble by blending information across locations through
      regularization with what we term an aggregating penalty. Our so called, Local
      Aggregate Model, can be fit in a completely distributed manner over the locations
      using an Alternating Direction Method of Multipliers (ADMM) strategy, and thus
      greatly reduces the computational burden. Furthermore, we propose to select the
      appropriate model through a novel sequence of faster algorithmic solutions that
      is similar to regularization paths. We will demonstrate both the computational
      and predictive modeling advantages of our methods via simulations and an EEG
      classification problem. 

PMID- 26295450
TI  - Comparison of mechanical testing methods for biomaterials: Pipette aspiration,
      nanoindentation, and macroscale testing.
AB  - Characterization of the mechanical properties of biological materials is often
      complicated by small volume, irregular geometry, fragility, and environmental
      sensitivity. Pipette aspiration and nanoindentation testing deal well with these
      limitations and have seen increasing use in biomaterial characterization, but
      little research has been done to systematically validate these techniques for
      soft materials. This study compared the results of pipette aspiration,
      nanoindentation, and bulk uniaxial tension and compression in determining the
      small-strain elastic moduli of a range of biomedically-relevant materials, a
      series of silicone elastomers and polyacrylamide hydrogels. A custom apparatus
      was developed for pipette aspiration testing, a commercial Hysitron instrument
      with custom spherical tip was used for nanoindentation, and standard commercial
      machines were used for tension and compression testing. The measured small-strain
      elastic moduli ranged from 27 to 368 kPa for the silicones and 11 to 44 kPa for
      the polyacrylamide gels. All methods detected expected trends in material
      stiffness, except for the results from one inconsistent silicone. Pipette
      aspiration and nanoindentation measured similar elastic moduli for silicone
      materials, but pipette aspiration measured consistently larger stiffness in the
      hydrogels, which may be explained by the gels' resistance to tension. Despite the
      difference in size scale among the testing methods, size does not appear to
      influence the results. These results suggest that both pipette aspiration and
      nanoindentation are suitable for measuring mechanical properties of soft
      biomaterials and appear to have no more limitations than bulk techniques.

PMID- 26295451
TI  - Influence of test specimen fabrication method and cross-section configuration on
      tension-tension fatigue life of PMMA bone cement.
AB  - Different cyclic loading modes have been used in in vitro fatigue studies of PMMA
      bone cement. It is unclear which loading mode is most appropriate from the
      perspective of the in vivo loading experienced by the cement in a cemented
      arthroplasty. Also, in different in vitro fatigue studies, different test
      specimen configurations have been used. The present work considers the influence
      of test specimen fabrication method (direct moulding vs moulding followed by
      machining) and cross-section shape (rectangular vs circular) on the tension
      tension fatigue performance of two bone cement brands (SmartSet GHV and CMW1),
      under force control conditions. Two trends were consistent: 1) for each of the
      cements, for moulded specimens, a longer fatigue life was obtained with circular
      cross-sectioned specimens and, 2) for either rectangular or circular CMW1
      specimens, a longer fatigue life was obtained using machined specimens. A
      comparison of the present results to those reported in our previous work on fully
      reversed tension-compression loading under force control showed that, regardless
      of the test specimen fabrication method or cross-section configuration used, the
      fatigue life was considerably shorter under tension-compression than tension
      tension loading. This finding highlights the fact that the presence of the
      compression portion in the loading cycle accelerates fatigue failure. 

PMID- 26295452
TI  - There is no such thing as infant sleep, there is no such thing as breastfeeding,
      there is only breastsleeping.

PMID- 26295453
TI  - Explaining the variability of the photochemical reflectance index (PRI) at the
      canopy-scale: Disentangling the effects of phenological and physiological
      changes.
AB  - Assessing photosynthesis rates at the ecosystem scale and over large regions is
      important for tracking the global carbon cycle and remote sensing has provided
      new and useful approaches for performing this assessment. The photochemical
      reflectance index (PRI) is a good estimator of short-term light-use efficiency
      (LUE) at the leaf scale; however, confounding factors appear at larger temporal
      and spatial scales. In this study, canopy-scale PRI variability was investigated
      for three species (Fagus sylvatica L., Quercus robur L. and Pinus sylvestris L.)
      growing under contrasting soil moisture conditions. Throughout the growing
      season, no significant differences in chlorophyll content and in violaxanthin,
      antheraxanthin and zeaxanthin were found between species or treatments. The daily
      PRI vs PAR (photosynthetically active radiation) relationships were determined
      using continuous measurements obtained at high frequency throughout the entire
      growing season, from early spring budburst to later autumn senescence, and were
      used to deconvolute the physiological PRI variability related to LUE variations
      due to phenological variability and related to temporal changes in the
      biochemical and structural canopy attributes. The PRI vs PAR relationship is used
      to show that the canopy-scale PRI measured at low radiation depends on the
      chlorophyll content of the canopy. The range of PRI variations at an intra-daily
      scale and the dynamics of the xanthophyll pool do not vary between days, which
      suggests that the PRI responds to a xanthophyll ratio. The PAR values at PRI
      saturation are mainly related to the canopy chlorophyll content during budburst
      and senescence and to the soil moisture content when the chlorophyll content is
      no longer a limiting factor. This parameter is significantly lower in the oak
      species that experience less stress from variations in soil moisture and is
      species dependant. These results provide new insights regarding the analysis and
      the meaning of PRI variability as a proxy for LUE at the canopy scale. 

PMID- 26295454
TI  - Does replacement of vitamin D reduce the symptom scores and improve quality of
      life in patients with chronic urticaria?
AB  - BACKGROUND: Vitamin D plays a key role in the immune responses generated by
      lymphocytes and antigen-presenting cells. Decreased vitamin 25-hydroxyvitamin D
      (25(OH)D) levels have been implicated in several allergic disorders and
      association between 25(OH)D levels and chronic urticaria (CU) symptom scores has
      been evaluated in a few studies. This study was performed to assess the effects
      of vitamin D supplementation on the symptoms and quality of life scores in
      chronic spontaneous urticaria (CSU) and to vitamin D levels in CSU patients in
      comparison with controls. PATIENTS AND METHODS: Fifty-eight CSU patients and
      forty-five controls were included in the study. The patients were divided into
      two groups according to severity of the disease; as mild/moderate and severe
      urticaria. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were measured in
      serum of CSU patients and compared with the control groups. In patients with
      25(OH)D concentrations lower than 30 ug/L, 300 000 IU/month of vitamin D3
      supplementation was added to standard therapy. The clinical improvement was
      evaluated after 3 months with urticaria activity score (UAS4) and Chronic
      Urticaria Quality of Life Questionnaire (CU-Q2oL). RESULTS: Serum 25(OH)D
      concentration was significantly lower in CSU group compared to healthy subjects
      (p < 0.001). The prevalence of vitamin D deficiency (<20 (ug/L) and insufficiency
      (<30 ug/L) was significantly higher in CSU patients than control groups. In
      addition, 25(OH)D concentrations were significantly lower in both mild-moderate
      and severe CSU patients than those of the controls (p = 0.011 and p < 0.001,
      respectively). Ninety eight percent of patients (25(OH)D < 30 ug/L) were treated
      with vitamin D3 (300 000 IU/month) supplementation, and after 12 weeks, these
      patients showed significant improvements in UAS4 and CU-Q2oL scores. CONCLUSION:
      This study support the contributing and beneficial effects of vitamin D in the
      treatment of CU. Replacement of vitamin D may provide improvement in both the
      severity of symptoms and the quality of life scores in these patients.

PMID- 26295455
TI  - Continuous vaccinations of 4Abeta1-15 induces specific fluctuation of
      inflammatory factors accompany with pathologic alterations alleviation in APP/PS1
      mice.
AB  - The common pathological hallmark of Alzheimer's disease (AD) is beta-amyloid
      plaques deposition. Immunotherapy is a revolutionary pharmacological treatment
      for AD, aiming at improving plaque clearance while concomitantly decreasing
      inflammation. Our previous study prepared antigen 4Abeta1-15 and found that it
      could alleviate pathologic alterations in APP/PS1 transgenic mice. The objective
      of our study was to research the changing processes induced by immunotherapy,
      including the inflammatory factor levels and microglial activation that is
      closely associated with Abeta burdens clearance. APP/PS1 mice were injected with
      4Abeta1-15 6 times. Each time, the inflammatory factors in sera were detected,
      and a specific fluctuation that first increased and then decreased was found, in
      which there was a turning point after the third injection. It prompted us to
      further detect the indicators in the brains after the third injection and the
      sixth injection. The results showed that the therapeutic effects for Abeta
      burdens and behaviors were continuously improved during the whole immune
      processes, whereas the inflammatory factor levels and microglial activation
      experienced similar specific fluctuations. The novel discovery may provide
      convenient methods for further detection and evaluation of immunotherapy in
      disease courses.

PMID- 26295456
TI  - OP9 Stromal Cells Proteins Involved in Hematoendothelial Differentiation from
      Human Embryonic Stem Cells.
AB  - Hematopoietic cells (HCs) and endothelial cells (ECs) can be produced in vitro
      from human embryonic stem cells (hESCs), but the differentiation systems used are
      still inefficient. To overcome this obstacle, it is necessary to understand the
      differentiation process. One of the methods used to obtain HCs and ECs from hESCs
      is their co-culture with stromal cells. The soluble factors secreted by these
      cells and cell-cell contact have a great impact on the differentiation process.
      Here, we performed comparative proteomic analyses of proteins obtained from the
      total extract of OP9 stromal cells and secreted by these cells before and during
      in vitro generation of HCs and ECs (hematoendothelial) from hESCs. We identified
      a total of 83 secreted and 759 intracellular proteins during differentiation.
      Twenty-five secreted and 181 proteins from the total extract were more abundant.
      Some secreted proteins are involved in cell-matrix interactions and HC and/or EC
      development. Moreover, 13 proteins of the total extract from OP9 cells that were
      exclusive/or more abundant during differentiation are involved in the Nrf2/Nfe2l2
      gene pathway, that is, they are described to have a key role in oxidative stress
      and in hematopoietic development and maturation. Our proteomic profiles provide
      valuable insight about the proteins involved in in vitro hematoendothelial cell
      generation and in the future they might be used to optimize the differentiation
      process and produce both cell types in vitro. 

PMID- 26295457
TI  - Biophysical Characterization of a Vaccine Candidate against HIV-1: The
      Transmembrane and Membrane Proximal Domains of HIV-1 gp41 as a Maltose Binding
      Protein Fusion.
AB  - The membrane proximal region (MPR, residues 649-683) and transmembrane domain
      (TMD, residues 684-705) of the gp41 subunit of HIV-1's envelope protein are
      highly conserved and are important in viral mucosal transmission, virus
      attachment and membrane fusion with target cells. Several structures of the
      trimeric membrane proximal external region (residues 662-683) of MPR have been
      reported at the atomic level; however, the atomic structure of the TMD still
      remains unknown. To elucidate the structure of both MPR and TMD, we expressed the
      region spanning both domains, MPR-TM (residues 649-705), in Escherichia coli as a
      fusion protein with maltose binding protein (MBP). MPR-TM was initially fused to
      the C-terminus of MBP via a 42 aa-long linker containing a TEV protease
      recognition site (MBP-linker-MPR-TM). Biophysical characterization indicated that
      the purified MBP-linker-MPR-TM protein was a monodisperse and stable candidate
      for crystallization. However, crystals of the MBP-linker-MPR-TM protein could not
      be obtained in extensive crystallization screens. It is possible that the 42
      residue-long linker between MBP and MPR-TM was interfering with crystal
      formation. To test this hypothesis, the 42 residue-long linker was replaced with
      three alanine residues. The fusion protein, MBP-AAA-MPR-TM, was similarly
      purified and characterized. Significantly, both the MBP-linker-MPR-TM and MBP-AAA
      MPR-TM proteins strongly interacted with broadly neutralizing monoclonal
      antibodies 2F5 and 4E10. With epitopes accessible to the broadly neutralizing
      antibodies, these MBP/MPR-TM recombinant proteins may be in immunologically
      relevant conformations that mimic a pre-hairpin intermediate of gp41. 

PMID- 26295459
TI  - Streamlined, Inexpensive 3D Printing of the Brain and Skull.
AB  - Neuroimaging technologies such as Magnetic Resonance Imaging (MRI) and Computed
      Tomography (CT) collect three-dimensional data (3D) that is typically viewed on
      two-dimensional (2D) screens. Actual 3D models, however, allow interaction with
      real objects such as implantable electrode grids, potentially improving patient
      specific neurosurgical planning and personalized clinical education. Desktop 3D
      printers can now produce relatively inexpensive, good quality prints. We describe
      our process for reliably generating life-sized 3D brain prints from MRIs and 3D
      skull prints from CTs. We have integrated a standardized, primarily open-source
      process for 3D printing brains and skulls. We describe how to convert clinical
      neuroimaging Digital Imaging and Communications in Medicine (DICOM) images to
      stereolithography (STL) files, a common 3D object file format that can be sent to
      3D printing services. We additionally share how to convert these STL files to
      machine instruction gcode files, for reliable in-house printing on desktop, open
      source 3D printers. We have successfully printed over 19 patient brain
      hemispheres from 7 patients on two different open-source desktop 3D printers.
      Each brain hemisphere costs approximately $3-4 in consumable plastic filament as
      described, and the total process takes 14-17 hours, almost all of which is
      unsupervised (preprocessing = 4-6 hr; printing = 9-11 hr, post-processing = <30
      min). Printing a matching portion of a skull costs $1-5 in consumable plastic
      filament and takes less than 14 hr, in total. We have developed a streamlined,
      cost-effective process for 3D printing brain and skull models. We surveyed
      healthcare providers and patients who confirmed that rapid-prototype patient
      specific 3D models may help interdisciplinary surgical planning and patient
      education. The methods we describe can be applied for other clinical, research,
      and educational purposes. 

PMID- 26295458
TI  - Detection of Cytomegalovirus Antibodies Using a Biosensor Based on Imaging
      Ellipsometry.
AB  - BACKGROUND: Cytomegalovirus (CMV) is the most common infectious cause of mental
      disability in newborns in developed countries. There is an urgent need to
      establish an early detection and high-throughput screening method for CMV
      infection using portable detection devices. METHODS: An antibody analysis method
      is reported for the detection and identification of CMV antibodies in serum using
      a biosensor based on high spatial resolution imaging ellipsometry (BIE). CMV
      antigen (CMV-3A) was immobilized on silicon wafers and used to capture CMV
      antibodies in serum. An antibody against human immunoglobulin G (anti-IgG) was
      used to confirm the IgG antibody against CMV captured by the CMV-3A. RESULTS: Our
      results show that this assay is rapid and specific for the identification of IgG
      antibody against CMV. Further, patient serum was quantitatively assessed using
      the standard curve method, and the quantitative results were in agreement with
      the enzyme-linked immunosorbent assay. The CMV antibody detection sensitivity of
      BIE reached 0.01 IU/mL. CONCLUSIONS: This novel biosensor may be a valuable
      diagnostic tool for analysis of IgG antibody against CMV during CMV infection
      screening.

PMID- 26295460
TI  - Strand displacement activated peroxidase activity of hemin for fluorescent DNA
      sensing.
AB  - To efficiently regulate the catalytic activity of the peroxidase mimic hemin,
      this work designs a double-stranded DNA probe containing an intermolecular dimer
      of hemin, whose peroxidase activity can be activated by a DNA strand displacement
      reaction. The double-stranded probe is prepared by annealing two strands of hemin
      labelled DNA oligonucleotides. Using the fluorescent oxidation product of
      tyramine by H2O2 as a tracing molecule, the low peroxidase activity of the hemin
      dimer ensures a low fluorescence background. The strand displacement reaction of
      the target DNA dissociates the hemin dimer and thus significantly increases the
      catalytic activity of hemin to produce a large amount of dityramine for
      fluorescence signal readout. Based on the strand displacement regulated
      peroxidase activity, a simple and sensitive homogeneous fluorescent DNA sensing
      method is proposed. The detection can conveniently be carried out in a 96-well
      plate within 20 min with a detection limit of 0.18 nM. This method shows high
      specificity, which can effectively distinguish single-base mismatched DNA from
      perfectly matched target DNA. The DNA strand displacement regulated catalytic
      activity of hemin has promising application in the determination of various DNA
      analytes. 

PMID- 26295462
TI  - The Immucillins: Design, Synthesis and Application of Transition- State
      Analogues.
AB  - Transition-state analysis based on kinetic isotope effects and computational
      chemistry provides electrostatic potential maps to serve as blueprints for the
      design and chemical synthesis of transition-state analogues. The utility of these
      molecules is exemplified by potential clinical applications toward leukemia,
      autoimmune disorders, gout, solid tumors, bacterial quorum sensing and bacterial
      antibiotics. In some cases, transition-state analogues have chemical features
      that have allowed them to be repurposed for new indications, including potential
      antiviral use. Three compounds from this family have entered clinical trials. The
      transition-state analogues bind to their target proteins with high affinity and
      specificity. The physical and structural properties of binding teach valuable and
      often surprising lessons about the nature of tight-binding inhibitors. 

PMID- 26295461
TI  - Sesterterpenoids with Anticancer Activity.
AB  - Terpenes have received a great deal of attention in the scientific literature due
      to complex, synthetically challenging structures and diverse biological
      activities associated with this class of natural products. Based on the number of
      C5 isoprene units they are generated from, terpenes are classified as hemi- (C5),
      mono- (C10), sesqui- (C15), di- (C20), sester- (C25), tri (C30), and
      tetraterpenes (C40). Among these, sesterterpenes and their derivatives known as
      sesterterpenoids, are ubiquitous secondary metabolites in fungi, marine
      organisms, and plants. Their structural diversity encompasses carbotricyclic
      ophiobolanes, polycyclic anthracenones, polycyclic furan-2-ones, polycyclic
      hydroquinones, among many other carbon skeletons. Furthermore, many of them
      possess promising biological activities including cytotoxicity and the associated
      potential as anticancer agents. This review discusses the natural sources that
      produce sesterterpenoids, provides sesterterpenoid names and their chemical
      structures, biological properties with the focus on anticancer activities and
      literature references associated with these metabolites. A critical summary of
      the potential of various sesterterpenoids as anticancer agents concludes the
      review. 

PMID- 26295463
TI  - Nicotinamide Adenine Dinucleotide Based Therapeutics, Update.
AB  - About 500 NAD (P)-dependent enzymes in the cell use NAD (P) as a cofactor or a
      substrate. This family of broadly diversified enzymes is crucial for maintaining
      homeostasis of all living organisms. The NAD binding domain of these enzymes is
      conserved and it was believed that NAD mimics would not be of therapeutic value
      due to lack of selectivity. Consequently, only mycophenolic acid which
      selectively binds at the cofactor pocket of NAD-dependent IMP-dehydrogenase
      (IMPDH) has been approved as an immunosuppressant. Recently, it became clear that
      the NAD (P)-binding domain was structurally much more diversified than
      anticipated and numerous highly potent and selective inhibitors of NAD (P)
      dependent enzymes have been reported. It is likely, that as in the case of
      protein kinases inhibitors, inhibitors of NAD (P)-dependent enzymes would find
      soon their way to the clinic. In this review, recent developments of selective
      inhibitors of NAD-dependent human IMPDH, as well as inhibitors of IMPDHs from
      parasites, and from bacterial sources are reported. Therapies against
      Cryptosporidium parvum and the development of new antibiotics that are on the
      horizon will be discussed. New inhibitors of bacterial NAD-ligases, NAD-kinases,
      NMN-adenylyl transferases, as well as phosphoribosyl transferases are also
      described. Although none of these compounds has yet to be approved, the progress
      in revealing and understanding crucial factors that might allow for designing
      more potent and efficient drug candidates is enormous and highly encouraging. 

PMID- 26295464
TI  - Nalmefene: A Novel Drug for an Old Disorder.
AB  - Alcoholism is an increasing problem all over the world, and nowadays especially
      amongst teenagers. Although several drug treatments have been proposed for this
      condition, only a few have demonstrated a significant efficacy. Nalmefene, a
      novel compound that combines opioids mu-receptors antagonism and kappa-receptors
      partial agonism, was recently approved by the European Medicine Agency for the
      treatment of alcoholism. This drug can be very helpful in reducing the alcohol
      intake, and, as such, it can be considered one of the first and fundamental steps
      towards alcohol abstinence. The aim of this review is to discuss and comment on
      the available literature on nalmefene, as well as on novel treatment strategies
      of this condition (and perhaps of other addictions) opened by this latest
      pharmacological approach. 

PMID- 26295465
TI  - Angiotensin II Type 1 Receptor Binding Molecule ATRAP as a Possible Modulator of
      Renal Sodium Handling and Blood Pressure in Pathophysiology.
AB  - Exaggerated activation of the renin-angiotensin system via tissue angiotensin II
      (Ang II) type 1 receptor (AT1R) signaling exerts detrimental effects on
      cardiovascular, renal and endocrine systems to provoke hypertension and related
      target organ damage. On the other hand, accumulated research evidence of both
      basic and clinical studies shows that physiological AT1R signaling also plays an
      indispensable role for the normal organ development such as the kidney and the
      maintenance of cardiovascular and renal homeostasis. Such functional diversity of
      AT1R signaling prompts us to seek a new strategy of selective modulation of AT1R
      signaling in pathophysiology. In the course of an investigational search for a
      means to functionally and selectively modulate AT1R signaling for that purpose, a
      molecule directly interacting with the carboxyl-terminal cytoplasmic domain of
      AT1R was identified by employing yeast two-hybrid screening of a mouse kidney
      cDNA library and named AT1R-associated protein (ATRAP). The results of functional
      analysis showed that ATRAP promotes constitutive AT1R internalization in cultured
      cells and inhibits Ang II-mediated pathological response in mouse distal
      convoluted cells. The ATRAP is expressed in a variety of tissues including the
      kidney where ATRAP is abundantly distributed in epithelial cells along the renal
      tubules. The results employing genetic engineered mice with modified ATRAP
      expression showed that ATRAP plays a key role in the regulation of renal sodium
      handling and the modulation of blood pressure in response to pathological stimuli
      such as chronic Ang II infusion, and suggest ATRAP to be a target of interest. 

PMID- 26295466
TI  - Structural Properties of Potential Synthetic Vaccine Adjuvants - TLR Agonists.
AB  - Toll like receptors (TLRs) are a family of transmembrane proteins which play a
      key role in innate immunity. When TLRs come into contact with a potential threat,
      they initiate a signaling cascade leading to release of cytokines and chemokines,
      maturation of antigen presenting cells and immune activation. Molecules which can
      activate TLRs may be utilized for vaccine development and act as vaccine
      adjuvants. Adjuvants can facilitate production of more effective vaccines based
      on antigens produced by recombinant techniques or by DNA vaccines, which are
      often poorly immunogenic since they lack the endogenous innate immunostimulatory
      components of the pathogen. In this paper the structural properties of such
      prospective compounds are thoroughly discussed. 

PMID- 26295467
TI  - Novel Drug Therapies for Fertility Preservation in Men Undergoing Chemotherapy:
      Clinical Relevance of Protector Agents.
AB  - Cancer has been affecting a growing number of children, adolescents and adult
      males in reproductive age. Male reproductive potential is adversely affected by
      chemotherapeutic drugs and patients are at risk for prolonged infertility.
      Fertility recovery is related to the chemotherapeutic agent and dosage used,
      being thus difficult to predict. As a result, there is a strong need to identify
      a natural or synthetic compound that is able to preserve male fertility without
      interfering with the efficacy of the chemotherapeutic regimen. New procedures, as
      well as several drugs, are being investigated to assess their efficiency in
      protecting male reproductive functions from the chemotherapy side-effects. This
      review provides an overview of the wide range of chemotherapeutic drugs regularly
      used in cancer treatment and their detrimental effects on male fertility. In
      addition, it also assesses the existing protector agents for male fertility and
      their usefulness in preserving and protecting male reproductive functions exposed
      to chemotherapeutics. Several protector agents for male fertility are being
      studied, and results are promising. Nonetheless, further research must be
      implemented to identify a supplemental therapy that addresses the multiple side
      effects of chemotherapy on male reproductive function. Until such therapy is
      discovered, it is fundamental that all fertility preservation options are
      discussed with patients, before treatment is initiated, to assure parenthood. 

PMID- 26295468
TI  - Current and Future Trends in Early Detection of Pancreatic Cancer: Molecular
      Targets and PET Probes.
AB  - Early detection of pancreatic cancer has been a long-standing challenge in
      determining prognosis and management of the deadly disease. Although the
      incidence of pancreatic cancer is low (2% of all malignancies), it is the fourth
      leading cause of deaths attributable to cancer in the U.S. A major cause for the
      high mortality rate, which exceeds 85%, is the difficulty in diagnosing the
      disease early in its development. The relative lack of reliable diagnostic tools
      to screen patients who are asymptomatic prior to the aggressive progression of
      disease has been the primary contributing factor in the high mortality rate in
      this patient population. Indeed, 80-90% of patients with pancreatic cancer have
      relatively small unresectable tumors at the time of diagnosis. Therefore, there
      is an unmet need for a highly sensitive diagnostic imaging modality to detect
      early-stage pancreatic cancer, as this may save the lives of many thousands of
      patients. Many literature reviews have been published on various aspects of
      pancreatic cancer, including biology, screening, and therapy; however, limited
      information is available on early detection, especially the use of highly
      sensitive modalities such as positron emission tomography (PET). Current
      [(18)F]FDG/PET imaging combined with CT (PET/CT) lacks the necessary sensitivity
      and specificity for detection of small lesions (~2-3 mm) of pancreatic cancer
      that may be resectable and curable. Furthermore, accumulation of [(18)F]FDG in
      inflammatory tissue is a major problem; therefore, an appropriate PET tracer that
      is both highly sensitive and specific for carcinoma is necessary for PET imaging
      of early stage pancreatic cancer. This review focuses on early detection of
      pancreatic cancer by PET, including new targets and the development and
      application of new PET tracers. 

PMID- 26295469
TI  - Over-Expressed Twist Associates with Markers of Epithelial Mesenchymal Transition
      and Predicts Poor Prognosis in Breast Cancers via ERK and Akt Activation.
AB  - Overexpression of Twist, a highly conserved basic helix-loop-helix transcription
      factor, is associated with epithelial-mesenchymal transition (EMT) and predicts
      poor prognosis in various kinds of cancers, including breast cancer. In order to
      further clarify Twist's role in breast cancer, we detected Twist expression in
      breast cancer tissues by immunohistochemistry. Twist expression was observed in
      54% (220/408) of breast cancer patients and was positively associated with tumor
      size, Ki67, VEGF-C and HER2 expression. Conversely, Twist was negatively
      associated with estrogen receptor (ER), progesterone receptor (PgR) and E
      cadherin expression. Patients with Twist expression had a poorer prognosis for 30
      month disease free survival (DFS) (82.9%) than patients with negative Twist
      (92.3%). Overexpression of Twist led to dramatic changes in cellular morphology,
      proliferation, migratory/invasive capability, and expression of EMT-related
      biomarkers in breast cancer cells. Moreover, we show that Twist serves as a
      driver of tumorigenesis, as well as an inducer of EMT, at least in part, through
      activation of the Akt and extracellular signal-regulated protein kinase (ERK)
      pathways which are critical for Twist-mediated EMT. Our results demonstrate that
      Twist expression is an important prognostic factor in breast cancer patients. 

PMID- 26295470
TI  - Creation of Mice Bearing a Partial Duplication of HPRT Gene Marked with a GFP
      Gene and Detection of Revertant Cells In Situ as GFP-Positive Somatic Cells.
AB  - It is becoming clear that apparently normal somatic cells accumulate mutations.
      Such accumulations or propagations of mutant cells are thought to be related to
      certain diseases such as cancer. To better understand the nature of somatic
      mutations, we developed a mouse model that enables in vivo detection of rare
      genetically altered cells via GFP positive cells. The mouse model carries a
      partial duplication of 3' portion of X-chromosomal HPRT gene and a GFP gene at
      the end of the last exon. In addition, although HPRT gene expression was thought
      ubiquitous, the expression level was found insufficient in vivo to make the
      revertant cells detectable by GFP positivity. To overcome the problem, we
      replaced the natural HPRT-gene promoter with a CAG promoter. In such animals,
      termed HPRT-dup-GFP mouse, losing one duplicated segment by crossover between the
      two sister chromatids or within a single molecule of DNA reactivates gene
      function, producing hybrid HPRT-GFP proteins which, in turn, cause the revertant
      cells to be detected as GFP-positive cells in various tissues. Frequencies of
      green mutant cells were measured using fixed and frozen sections (liver and
      pancreas), fixed whole mount (small intestine), or by means of flow cytometry
      (unfixed splenocytes). The results showed that the frequencies varied extensively
      among individuals as well as among tissues. X-ray exposure (3 Gy) increased the
      frequency moderately (~2 times) in the liver and small intestine. Further, in two
      animals out of 278 examined, some solid tissues showed too many GFP-positive
      cells to score (termed extreme jackpot mutation). Present results illustrated a
      complex nature of somatic mutations occurring in vivo. While the HPRT-dup-GFP
      mouse may have a potential for detecting tissue-specific environmental mutagens,
      large inter-individual variations of mutant cell frequency cause the results
      unstable and hence have to be reduced. This future challenge will likely involve
      lowering the background mutation frequency, thus reducing inter-individual
      variation. 

PMID- 26295471
TI  - Modulation of Estrogen Response Element-Driven Gene Expressions and Cellular
      Proliferation with Polar Directions by Designer Transcription Regulators.
AB  - Estrogen receptor alpha (ERalpha), as a ligand-dependent transcription factor,
      mediates 17beta-estradiol (E2) effects. ERalpha is a modular protein containing a
      DNA binding domain (DBD) and transcription activation domains (AD) located at the
      amino- and carboxyl-termini. The interaction of the E2-activated ERalpha dimer
      with estrogen response elements (EREs) of genes constitutes the initial step in
      the ERE-dependent signaling pathway necessary for alterations of cellular
      features. We previously constructed monomeric transcription activators, or
      monotransactivators, assembled from an engineered ERE-binding module (EBM) using
      the ERalpha-DBD and constitutively active ADs from other transcription factors.
      Monotransactivators modulated cell proliferation by activating and repressing ERE
      driven gene expressions that simulate responses observed with E2-ERalpha. We
      reasoned here that integration of potent heterologous repression domains (RDs)
      into EBM could generate monotransrepressors that alter ERE-bearing gene
      expressions and cellular proliferation in directions opposite to those observed
      with E2-ERalpha or monotransactivators. Consistent with this, monotransrepressors
      suppressed reporter gene expressions that emulate the ERE-dependent signaling
      pathway. Moreover, a model monotransrepressor regulated DNA synthesis, cell cycle
      progression and proliferation of recombinant adenovirus infected ER-negative
      cells through decreasing as well as increasing gene expressions with polar
      directions compared with E2-ERalpha or monotransactivator. Our results indicate
      that an 'activator' or a 'repressor' possesses both transcription
      activating/enhancing and repressing/decreasing abilities within a chromatin
      context. Offering a protein engineering platform to alter signal pathway-specific
      gene expressions and cell growth, our approach could also be used for the
      development of tools for epigenetic modifications and for clinical interventions
      wherein multigenic de-regulations are an issue. 

PMID- 26295472
TI  - Impact of Maternal Country of Birth on Type-1-Diabetes Therapy and Outcome in
      27,643 Children and Adolescents from the DPV Registry.
AB  - OBJECTIVE: To study the impact of maternal country of birth on type-1-diabetes
      (T1D) therapy and outcome. STUDY DESIGN AND METHODS: 27,643 T1D patients aged
      <=20 years with documented maternal country of birth from the multicenter
      German/Austrian diabetes patient registry (DPV) were analyzed. Patients were
      categorized based on their mother's origin: Germany/Austria (reference), Turkey,
      Southern Europe, and Eastern Europe. To compare BMI standard deviation score (BMI
      SDS), diabetes therapy and outcome between groups, multivariable regression was
      applied with adjustments for age, sex and duration of diabetes. Based on observed
      marginal frequencies, adjusted estimates were calculated. Linear regression was
      used for continuous data, logistic regression for binary data and Poisson
      regression for count data. All statistical analyses were performed using SAS 9.4.
      Significance was set at a two-tailed p<0.05. RESULTS: 83.3% of patients were
      offspring of native mothers. A Turkish, Southern or Eastern European background
      was documented in 2.4%, 1.7% and 4.3% of individuals. After demographic
      adjustment, patients with migration background had a higher mean BMI-SDS (Turkey,
      Southern Europe or Eastern Europe vs. Germany/Austria: 0.58+/-0.03, 0.40+/-0.04,
      or 0.37+/-0.02 vs. 0.31+/-0.01; +/-SE) and a lower use of insulin pumps (26.8%,
      27.9%, or 32.6% vs. 37.9%) compared to offspring of native mothers. Mean HbA1c
      was worst in individuals of Turkish mothers (Turkey vs. Germany/Austria: 69.7+/
      0.7 vs. 66.6+/-0.1 mmol/mol; +/-SE). Patients of Eastern European descent had an
      increased rate of severe hypoglycemia (22.09+/-0.13 vs. 16.13+/-0.02 events per
      100 patient-years) and ketoacidosis was more prevalent in offspring of Turkish or
      Southern European mothers (7.50+/-0.10, or 7.13+/-0.11 vs. 6.54+/-0.02 events per
      100 patient-years). Patients of Turkish descent were more often hospitalized
      (57.2+/-2.7 vs. 48.5+/-0.4 per 100 patient-years). All differences were
      significant. CONCLUSION: The differences in diabetes therapy and outcome among
      patients with distinct migration background suggest that specific challenges have
      to be considered in clinical care.

PMID- 26295473
TI  - Birth Cohort, Age, and Sex Strongly Modulate Effects of Lipid Risk Alleles
      Identified in Genome-Wide Association Studies.
AB  - Insights into genetic origin of diseases and related traits could substantially
      impact strategies for improving human health. The results of genome-wide
      association studies (GWAS) are often positioned as discoveries of unconditional
      risk alleles of complex health traits. We re-analyzed the associations of single
      nucleotide polymorphisms (SNPs) associated with total cholesterol (TC) in a large
      scale GWAS meta-analysis. We focused on three generations of genotyped
      participants of the Framingham Heart Study (FHS). We show that the effects of all
      ten directly-genotyped SNPs were clustered in different FHS generations and/or
      birth cohorts in a sex-specific or sex-unspecific manner. The sample size and
      procedure-therapeutic issues play, at most, a minor role in this clustering. An
      important result was clustering of significant associations with the strongest
      effects in the youngest, or 3rd Generation, cohort. These results imply that an
      assumption of unconditional connections of these SNPs with TC is generally
      implausible and that a demographic perspective can substantially improve GWAS
      efficiency. The analyses of genetic effects in age-matched samples suggest a role
      of environmental and age-related mechanisms in the associations of different SNPs
      with TC. Analysis of the literature supports systemic roles for genes for these
      SNPs beyond those related to lipid metabolism. Our analyses reveal strong
      antagonistic effects of rs2479409 (the PCSK9 gene) that cautions strategies aimed
      at targeting this gene in the next generation of lipid drugs. Our results suggest
      that standard GWAS strategies need to be advanced in order to appropriately
      address the problem of genetic susceptibility to complex traits that is
      imperative for translation to health care. 

PMID- 26295474
TI  - Epidemiological and Molecular Characterization of Dengue Virus Circulating in
      Bhutan, 2013-2014.
AB  - Dengue is one of the most significant public health problems in tropical and
      subtropical countries, and is increasingly being detected in traditionally non
      endemic areas. In Bhutan, dengue virus (DENV) has only recently been detected and
      limited information is available. In this study, we analyzed the epidemiological
      and molecular characteristics of DENV in two southern districts in Bhutan from
      2013-2014. During this period, 379 patients were clinically diagnosed with
      suspected dengue, of whom 119 (31.4%) were positive for DENV infection by NS1
      ELISA and/or nested RT-PCR. DENV serotypes 1, 2 and 3 were detected with DENV-1
      being predominant. Phylogenetic analysis of DENV-1 using envelope gene
      demonstrated genotype V, closely related to strains from northern India. 

PMID- 26295475
TI  - Correction: Modulating the RNA Processing and Decay by the Exosome: Altering
      Rrp44/Dis3 Activity and End-Product.

PMID- 26295476
TI  - Cool Headed Individuals Are Better Survivors: Non-Consumptive and Consumptive
      Effects of a Generalist Predator on a Sap Feeding Insect.
AB  - Non-consumptive effects (NCEs) of predators are part of the complex interactions
      among insect natural enemies and prey. NCEs have been shown to significantly
      affect prey foraging and feeding. Leafhopper's (Auchenorrhyncha) lengthy phloem
      feeding bouts may play a role in pathogen transmission in vector species and also
      exposes them to predation risk. However, NCEs on leafhoppers have been scarcely
      studied, and we lack basic information about how anti-predator behaviour
      influences foraging and feeding in these species. Here we report a study on non
      consumptive and consumptive predator-prey interactions in a naturally co
      occurring spider-leafhopper system. In mesocosm arenas we studied movement
      patterns during foraging and feeding of the leafhopper Psammotettix alienus in
      the presence of the spider predator Tibellus oblongus. Leafhoppers delayed
      feeding and fed much less often when the spider was present. Foraging movement
      pattern changed under predation risk: movements became more frequent and brief.
      There was considerable individual variation in foraging movement activity. Those
      individuals that increased movement activity in the presence of predators exposed
      themselves to higher predation risk. However, surviving individuals exhibited a
      'cool headed' reaction to spider presence by moving less than leafhoppers in
      control trials. No leafhoppers were preyed upon while feeding. We consider
      delayed feeding as a "paradoxical" antipredator tactic, since it is not
      necessarily an optimal strategy against a sit-and-wait generalist predator. 

PMID- 26295478
TI  - Local Variability Mediates Vulnerability of Trout Populations to Land Use and
      Climate Change.
AB  - Land use and climate change occur simultaneously around the globe. Fully
      understanding their separate and combined effects requires a mechanistic
      understanding at the local scale where their effects are ultimately realized.
      Here we applied an individual-based model of fish population dynamics to evaluate
      the role of local stream variability in modifying responses of Coastal Cutthroat
      Trout (Oncorhynchus clarkii clarkii) to scenarios simulating identical changes in
      temperature and stream flows linked to forest harvest, climate change, and their
      combined effects over six decades. We parameterized the model for four
      neighboring streams located in a forested headwater catchment in northwestern
      Oregon, USA with multi-year, daily measurements of stream temperature, flow, and
      turbidity (2007-2011), and field measurements of both instream habitat structure
      and three years of annual trout population estimates. Model simulations revealed
      that variability in habitat conditions among streams (depth, available habitat)
      mediated the effects of forest harvest and climate change. Net effects for most
      simulated trout responses were different from or less than the sum of their
      separate scenarios. In some cases, forest harvest countered the effects of
      climate change through increased summer flow. Climate change most strongly
      influenced trout (earlier fry emergence, reductions in biomass of older trout,
      increased biomass of young-of-year), but these changes did not consistently
      translate into reductions in biomass over time. Forest harvest, in contrast,
      produced fewer and less consistent responses in trout. Earlier fry emergence
      driven by climate change was the most consistent simulated response, whereas
      survival, growth, and biomass were inconsistent. Overall our findings indicate a
      host of local processes can strongly influence how populations respond to broad
      scale effects of land use and climate change. 

PMID- 26295477
TI  - Brazilin Limits Inflammatory Responses through Induction of Prosurvival Autophagy
      in Rheumatoid Fibroblast-Like Synoviocytes.
AB  - Brazilin is an active compound of Caesalpinia sappan L. (Leguminosae), which
      possesses pro-apoptotic and anti-inflammation potentials depending on the
      specific cell type. However, it is largely unknown whether autophagy is
      implicated in the mechanism underlying its chemotherapeutic and anti-inflammatory
      effects in rheumatoid arthritis (RA). Here, we show that treatment of RA
      fibroblast-like synoviocytes (FLS) with brazilin results in enhanced level of
      autophagic flux, evidenced by accumulation of autophagosome and increased level
      of lipidated LC3 (LC3-II), which is mainly mediated by enhanced production of
      reactive oxygen species (ROS). Interestingly, long-term exposure of brazilin was
      able to restore cell survival against the cytotoxity, exclusively in RA FLS, but
      not in normal fibroblast. Importantly, such a restoration from brazilin-induced
      cytotoxity in RA FLS was completely abrogated after co-treatment with autophagy
      inhibitors including NH4Cl or chloroquine. Furthermore, we found that the
      pretreatment of RA FLS with brazilin reduced LPS- or TNF-induced NF-kappaB
      activation and the secretion of inflammatory cytokines in parallel with the
      enhanced autophagic flux. Such anti-NF-kappaB potentials of brazilin were
      drastically masked in RA FLS when autophagy was suppressed. These results suggest
      that brazilin is capable of activating autophagy exclusively in RA FLS, and such
      inducible autophagy promotes cell survival and limits inflammatory response. 

PMID- 26295479
TI  - Influence of the R823W mutation on the interaction of the ANKS6-ANKS3: insights
      from molecular dynamics simulation and free energy analysis.
AB  - The sterile alpha motif (SAM) domain of the protein ANKS6, a protein-protein
      interaction domain, is responsible for autosomal dominant polycystic kidney
      disease. Although the disease is the result of the R823W point mutation in the
      SAM domain of the protein ANKS6, the molecular details are still unclear. We
      applied molecular dynamics simulations, the principal component analysis, and the
      molecular mechanics Poisson-Boltzmann surface area binding free energy
      calculation to explore the structural and dynamic effects of the R823W point
      mutation on the complex ANKS6-ANKS3 (PDB ID: 4NL9) in comparison to the wild
      proteins. The energetic analysis presents that the wild type has a more stable
      structure than the mutant. The R823W point mutation not only disrupts the
      structure of the ANKS6 SAM domain but also negatively affects the interaction of
      the ANKS6-ANKS3. These results further clarify the previous experiments to
      understand the ANKS6-ANKS3 interaction comprehensively. In summary, this study
      would provide useful suggestions to understand the interaction of these proteins
      and their fatal action on mediating kidney function. 

PMID- 26295480
TI  - Feature Selection and Pedestrian Detection Based on Sparse Representation.
AB  - Pedestrian detection have been currently devoted to the extraction of effective
      pedestrian features, which has become one of the obstacles in pedestrian
      detection application according to the variety of pedestrian features and their
      large dimension. Based on the theoretical analysis of six frequently-used
      features, SIFT, SURF, Haar, HOG, LBP and LSS, and their comparison with
      experimental results, this paper screens out the sparse feature subsets via
      sparse representation to investigate whether the sparse subsets have the same
      description abilities and the most stable features. When any two of the six
      features are fused, the fusion feature is sparsely represented to obtain its
      important components. Sparse subsets of the fusion features can be rapidly
      generated by avoiding calculation of the corresponding index of dimension numbers
      of these feature descriptors; thus, the calculation speed of the feature
      dimension reduction is improved and the pedestrian detection time is reduced.
      Experimental results show that sparse feature subsets are capable of keeping the
      important components of these six feature descriptors. The sparse features of HOG
      and LSS possess the same description ability and consume less time compared with
      their full features. The ratios of the sparse feature subsets of HOG and LSS to
      their full sets are the highest among the six, and thus these two features can be
      used to best describe the characteristics of the pedestrian and the sparse
      feature subsets of the combination of HOG-LSS show better distinguishing ability
      and parsimony. 

PMID- 26295481
TI  - Could a Factor That Does Not Affect Egg Recognition Influence the Decision of
      Rejection?
AB  - Rejection of the parasitic egg is the most important defence of hosts against
      brood parasites. However, this response is variable among and within species, and
      egg discrimination is not always followed by egg rejection. Low risk of
      parasitism and high risk of rejection costs may lead to the acceptance of the
      parasitic egg even if it has been previously recognized. The main aim of this
      paper is to answer a relevant question: can a single egg trait provoke the
      acceptance of an experimental egg previously recognized as foreign? Increased egg
      mass should hamper the ejection of an egg that has been discriminated because
      ejection of a heavy egg may imply higher rejection costs for hosts. We have
      tested this prediction by experimentally parasitizing natural nests of Common
      Blackbirds (Turdus merula) with non-mimetic model eggs of different mass (heavy,
      normal-weight, and light) while controlling for potential confounding factors
      such as egg size and colour. Our results showed that blackbirds more frequently
      accepted heavy eggs, even when previously recognized. This differential
      acceptance may be related to insufficient motivation to assume the higher costs
      that the ejection of a heavy egg could impose. 

PMID- 26295482
TI  - Determining brain fitness to fight: Has the time come?
AB  - Professional boxing is associated with a risk of chronic neurological injury,
      with up to 20-50% of former boxers exhibiting symptoms of chronic brain injury.
      Chronic traumatic brain injury encompasses a spectrum of disorders that are
      associated with long-term consequences of brain injury and remains the most
      difficult safety challenge in modern-day boxing. Despite these concerns,
      traditional guidelines used for return to sport participation after concussion
      are inconsistently applied in boxing. Furthermore, few athletic commissions
      require either formal consultation with a neurological specialist (i.e.
      neurologist, neurosurgeon, or neuropsychologist) or formal neuropsychological
      testing prior to return to fight. In order to protect the health of boxers and
      maintain the long-term viability of a sport associated with exposure to
      repetitive head trauma, we propose a set of specific requirements for brain
      safety that all state athletic commissions would implement. 

PMID- 26295483
TI  - The effects of black soybean (Glycine max var.) on chronic cervical pain of
      sedentary office workers in a northern Chinese population.
AB  - Chronic cervical pain is a common symptom of sedentary office workers. Black
      soybean (Glycine max var.) has rich necessary nutrients for the therapy of
      chronic pain. Thus, it may ease chronic cervical pain. To prove our claim, 260
      sedentary office workers with chronic pain were recruited and they consumed the
      defined diets at breakfast, lunch, and dinner with 1 g, 5 g and 10 g (3 g, 15 g,
      30 g daily) cooked black soybean for 24 weeks. Visual analog scale (VAS), neck
      disability index (NDI) pain scores and short-form 36 (SF-36) health survey
      questionnaires were applied in the study. The levels of N-methyl-D-aspartate
      receptors (NMDAR) were measured. The VAS and NDI pain scores reduced and SF-36
      scores increased in a 15 or 30 g black soybean daily group compared with a 3 g
      black soybean daily group after a 24-week therapy (P < 0.05). The 30 g black
      soybean daily group was better than the 15 g black soybean daily group in
      relieving chronic cervical pain of sedentary office workers (p < 0.05). The
      levels of NMDAR were lower in the 15 or 30 black soybean daily group than those
      in the 3 g black soybean daily group (P < 0.05). Black soybean can ameliorate
      chronic cervical pain by down-regulating the levels of NMDAR.

PMID- 26295484
TI  - Correction: Time-Course Gene Set Analysis for Longitudinal Gene Expression Data.

PMID- 26295485
TI  - Encephalitis Surveillance through the Emerging Infections Program, 1997-2010.
AB  - Encephalitis is a devastating illness that commonly causes neurologic disability
      and has a case fatality rate >5% in the United States. An etiologic agent is
      identified in <50% of cases, making diagnosis challenging. The Centers for
      Disease Control and Prevention Emerging Infections Program (EIP) Encephalitis
      Project established syndromic surveillance for encephalitis in New York,
      California, and Tennessee, with the primary goal of increased identification of
      causative agents and secondary goals of improvements in treatment and outcome.
      The project represents the largest cohort of patients with encephalitis studied
      to date and has influenced case definition and diagnostic evaluation of this
      condition. Results of this project have provided insight into well-established
      causal pathogens and identified newer causes of infectious and autoimmune
      encephalitis. The recognition of a possible relationship between enterovirus D68
      and acute flaccid paralysis with myelitis underscores the need for ongoing
      vigilance for emerging causes of neurologic disease. 

PMID- 26295486
TI  - The emerging role of multiple antiphospholipid antibodies positivity in patients
      with antiphospholipid syndrome.
AB  - Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by
      clinical symptoms of vascular thrombosis and/or pregnancy morbidity in the
      presence of autoimmune antiphospholipid antibodies (aPL). Current laboratory APS
      criteria include the presence of at least one of the three relevant aPL: lupus
      anticoagulant, anticardiolipin antibodies and anti-beta2 glycoprotein I
      antibodies. Therefore, patients could have a single aPL pattern or combinations
      of aPL. Evidence arising from clinical experience indicates that patients having
      the highest aPL titer and simultaneous aPL detected by different tests have a
      worse prognosis and a higher probability of recurrence of the APS clinical
      features. In recent years, an emerging role of multiple aPL positivity in the
      identification of high-risk patients with aPL/APS is evident. This paper will
      review the current knowledge on the clinical relevance of having single or
      multiple aPL positivity. 

PMID- 26295487
TI  - Psychosocial Health, e-Health Literacy, and Perceptions of e-Health as Predictors
      and Moderators of e-Health Use Among Caregivers of Children with Special
      Healthcare Needs.
AB  - OBJECTIVES: In this study, we explored the relationships between the psychosocial
      health of caregivers of children with special healthcare needs and their e-health
      use. Additionally, the analysis examined moderating effects of a caregiver's
      perceptions of e-health and his or her e-health literacy on the associations
      among four domains of psychosocial health and e-health use. MATERIALS AND
      METHODS: To date, 313 caregivers of children, 12-18 years of age, with special
      healthcare needs have been recruited. Covariate-adjusted multivariable
      regressions determined associations between psychosocial health domains of
      caregivers and e-health use. E-health literacy and perceptions of e-health were
      further tested as moderators of the relationship between psychosocial health and
      e-health use. RESULTS: Among the caregiver population, 31% had problems with
      social functioning, 36.1% with communication, 43.3% with family relationships,
      and 46.3% with worrying for their child. After adjusting for demographic
      variables, e-health use was associated with poorer levels of social functioning,
      communication, worry, and family relationship. E-health use was also associated
      with e-health literacy. Perceptions of e-health significantly moderated the
      relationships among social functioning, communication, and e-health, with the
      relationship being significantly stronger in caregivers with more positive
      perceptions of e-health. CONCLUSIONS: Caregivers of children with special
      healthcare needs have notable levels of psychosocial challenges and those
      challenges are associated with their e-health resource seeking. Although e-health
      interventions, including ones that focus on child health education and caregiver
      support, may be the future of healthcare, a concerted effort is needed to educate
      caregivers about the benefits of e-health.

PMID- 26295488
TI  - Exploring Winter Community Participation Among Wheelchair Users: An Online Focus
      Group.
AB  - The aim of this qualitative study was to gain an understanding of what people who
      use wheeled mobility devices (WMDs; e.g., manual and power wheelchairs, and
      scooters) identify as environmental barriers to community participation in cold
      weather climates, and to explore recommendations to overcome environmental
      barriers to community participation. Researchers conducted an online asynchronous
      focus group that spanned seven days, with eight individuals who use WMDs. Each
      day, participants were asked to respond to a moderator-provided question, and to
      engage with one another around the topic area. The researchers analyzed the
      verbatim data using an inductive content-analysis approach. Four categories
      emerged from the data: (1) winter barriers to community participation; (2) life
      resumes in spring and summer; (3) change requires awareness, education, and
      advocacy; and (4) winter participation is a right. Participants confirmed that it
      is a collective responsibility to ensure that WMD users are able to participate
      in the community throughout the seasons. 

PMID- 26295489
TI  - Phencyclidine analog use in Sweden--intoxication cases involving 3-MeO-PCP and 4
      MeO-PCP from the STRIDA project.
AB  - BACKGROUND: 3-Methoxy-phencyclidine (3-MeO-PCP) and 4-methoxy-phencyclidine (4
      MeO-PCP) are analogs of and drug substitutes for the dissociative substance PCP
      ("Angel dust"), a recreational drug that was most popular in the 1970s. In
      Sweden, use of methoxylated PCP analogs was noted starting in mid-2013, according
      to statistics from the Poisons Information Centre. The objective of this case
      series was to present clinical and bioanalytical data from analytically confirmed
      non-fatal intoxications associated with 3-MeO-PCP and/or 4-MeO-PCP within the
      STRIDA project. STUDY DESIGN: Observational case series of consecutive patients
      with self-reported or suspected exposure to new psychoactive substances (NPS) and
      who require hospital care. PATIENTS AND METHODS: Blood and urine samples were
      collected from intoxicated patients presenting at emergency departments (ED) or
      intensive care units (ICU) all over Sweden. NPS analysis was performed by
      multicomponent liquid chromatographic-tandem mass spectrometric (LC-MS/MS) and LC
      high-resolution MS (LC-HRMS) methods. Data on clinical features were collected
      during Poisons Information Centre consultations and retrieved from medical
      records. RESULTS: The Poisons Information Centre registered its first call
      related to methoxylated PCP analogs in July 2013, while analytically confirmed
      cases first appeared in October 2013. From July 2013 to March 2015, 1243 cases of
      suspected NPS intoxication originating from ED or ICU were enrolled in the STRIDA
      project. During the 21-month period, 56 (4.5%) patients tested positive for 3-MeO
      PCP and 11 (0.9%) for 4-MeO-PCP; 8 of these cases involved both substances. The
      59 patients were aged 14-55 (median: 26) years and 51 (86%) were men. Co-exposure
      to other NPSs and/or classical drugs of abuse was common with only 7 cases (12%)
      indicated to be 3-MeO-PCP single-substance intoxications; prominent clinical
      signs seen in the latter cases were hypertension (systolic blood pressure >= 140
      mmHg; 7 cases), tachycardia (>= 100/min; 5 cases), and altered mental status (4
      cases) including confusion, disorientation, dissociation, and/or hallucinations.
      Mixed-drug users displayed not only the same clinical features, but also more
      sympathomimetic effects including agitation (38%) and dilated pupils (33%).
      Patients testing positive for 3-/4-MeO-PCP were typically under medical care for
      1-2 days (85%), and 37% of all cases were graded as severe intoxications
      (Poisoning Severity Score 3). Besides standard supportive therapy, 49% of the
      patients were treated with benzodiazepines and/or propofol. CONCLUSION:
      Laboratory analysis constitutes an important basis for the assessment of NPS
      hazard and availability. The adverse effects noted in cases of acute
      intoxications involving 3- and/or 4-MeO-PCP resembled those of other
      dissociatives such as PCP, ketamine, and methoxetamine. However, similar to
      intoxications involving other NPS, poly-substance use was found to be common.

PMID- 26295490
TI  - Reversing Fetal Undernutrition by Kick-Starting Early Growth.

PMID- 26295492
TI  - A Vagina Monologue: Mom's Stress, Bugs, and Baby's Brain.

PMID- 26295495
TI  - Copper-Catalyzed Ligand-Free Amidation of Benzylic Hydrocarbons and Inactive
      Aliphatic Alkanes.
AB  - An efficient copper-catalyzed amidation of benzylic hydrocarbons and inactive
      aliphatic alkanes with simple amides was developed. The protocol proceeded
      smoothly without any ligand, and a wide range of N-alkylated aromatic and
      aliphatic amides, sulfonamides, and imides were synthesized in good yields. 

PMID- 26295491
TI  - A Kiss and a PRomise.

PMID- 26295496
TI  - Mitochondria and DNA Targeting of 5,10,15,20-Tetrakis(7
      sulfonatobenzo[b]thiophene) Porphyrin-Induced Photodynamic Therapy via Intrinsic
      and Extrinsic Apoptotic Cell Death.
AB  - Photodynamic therapy (PDT) selectively targets subcellular organelles and
      promises an excellent therapeutic strategy for cancer treatment. Here, we report
      the synthesis of a new water-soluble photosensitizer, 5,10,15,20-tetrakis (7
      sulfonatobenzo[b]thiophene) porphyrin (SBTP). Rational design of the porphyrinic
      molecule containing benzo[b]thiophene moiety at the meso-position led to
      selective accumulation in both mitochondria and nucleus of MCF-7 cells. This
      multitarget ability of SBTP can cause damage to mitochondria as well as DNA
      simultaneously. FACS analysis showed rapid cellular uptake of SBTP. High-content
      cell-based assay was executed to concurrently monitor increase of cytosolic
      Ca(2+) levels, mitochondrial permeability transition (MPT), and caspase-3/7/8
      activation in MCF-7 cells under the pathological condition caused by PDT action
      of SBTP. The study of cell death dynamics showed that PDT action of SBTP caused
      an increase in the MPT followed by an increase in cytosolic Ca(2+) level. The
      localization of SBTP in the mitochondria activated the intrinsic apoptotic
      pathway. Additionally, localization of SBTP in the nucleus led to DNA damage in
      MCF-7 cells. The DNA fragmentation that occurred by PDT action of SBTP was
      thought to be responsible for extrinsic apoptosis of MCF-7 cells. SBTP
      demonstrated effective PDT activity of 5 MUM IC50 value to MCF-7 cells by
      bitargeting mitochondria and DNA. 

PMID- 26295497
TI  - The Social Context of Depression Symptomology in Sexual Minority Male Youth:
      Determinants of Depression in a Sample of Grindr Users.
AB  - The purpose of this study was to understand which social context factors most
      influence depression symptomology among sexual minority male youth (SMMY). In
      2011, 195 SMMY who use Grindr were recruited to complete an online survey in Los
      Angeles, California. Items focused on social context variables and depression
      symptomology. Hierarchical multiple regressions were conducted using an
      ecological framework. The best fitting model accounted for 29.5% of the variance
      in depression. Experiences of homophobia, gay community connection, presence of
      an objecting network member, and emotional support were found to be significant
      predictors. Past experiences of homophobia continuing to affect youth indicates
      the need for intervention to reduction of homophobia in youths' social contexts.
      Interventions that teach youth skills to manage objecting viewpoints or help
      youth to reorganize their social networks may help to reduce the impact of an
      objecting network alter. 

PMID- 26295500
TI  - Endoscopic Third Ventriculostomy in 250 Adults With Hydrocephalus: Patient
      Selection, Outcomes, and Complications.
AB  - BACKGROUND: Endoscopic third ventriculostomy (ETV) has been used predominantly in
      the pediatric population in the past. Application in the adult population has
      been less extensive, even in large neurosurgical centers. To our knowledge, this
      report is one of the largest adult ETV series reported and has the consistency of
      being performed at 1 center. OBJECTIVE: To determine the efficacy, safety, and
      outcome of ETV in a large adult hydrocephalus patient series at a single
      neurosurgical center. In addition, to analyze patient selection criteria and
      clinical subgroups (including those with ventriculoperitoneal shunt [VPS]
      malfunction or obstruction and neurointensive care unit patients with extended
      ventricular drainage before ETV) to optimize surgical results in the future.
      METHODS: We conducted a retrospective review of adult ETV procedures performed at
      our center between 2000 and 2014. RESULTS: The overall rate of success (no
      further cerebrospinal fluid diversion procedure performed plus clinical
      improvement) of 243 completed ETVs was 72.8%. Following is the number of
      procedures with the success rate in parentheses: aqueduct stenosis, 56 (91%);
      communicating hydrocephalus including normal pressure hydrocephalus, nonnormal
      pressure hydrocephalus, and remote head trauma, 57 (43.8%); communicating
      hydrocephalus in postoperative posterior fossa tumor without residual tumor, 14
      (85.7%); communicating hydrocephalus in subarachnoid hemorrhage without
      intraventricular hemorrhage, 23 (69.6%); obstruction from tumor/cyst, 42 (85.7%);
      VPS obstruction (diagnosis unknown), 23 (65.2%); intraventricular hemorrhage, 20
      (90%); and miscellaneous (obstructive), 8 (50%). There were 9 complications in
      250 intended procedures (3.6%); 5 (2%) were serious. CONCLUSION: Use of ETV in
      adult hydrocephalus has broad application with a low complication rate and
      reasonably good efficacy in selected patients.

PMID- 26295501
TI  - Cyclic Square Wave Voltammetry of Surface-Confined Quasireversible Electron
      Transfer Reactions.
AB  - The theory for cyclic square wave voltammetry of surface-confined quasireversible
      electrode reactions is presented and experimentally verified. Theoretical
      voltammograms were calculated following systematic variation of empirical
      parameters to assess their impact on the shape of the voltammogram. From the
      trends obtained, diagnostic criteria for this mechanism were deduced. These
      criteria were experimentally confirmed using two well-established surface
      confined analytes. When properly applied, these criteria will enable non-experts
      in voltammetry to assign the electrode reaction mechanism and accurately measure
      electrode reaction kinetics. 

PMID- 26295502
TI  - Best Practices in Alemtuzumab Administration: Practical Recommendations for
      Infusion in Patients With Multiple Sclerosis.
AB  - With the growing complexity of multiple sclerosis (MS) care, nursing
      professionals have increasing responsibility in managing clinical disease and
      treatment. Nursing professionals and other health care providers play important
      roles in educating patients about disease-modifying therapy options, the course
      of therapy, and managing potential adverse effects. A panel of nursing and MS
      experts was convened and used a modified Delphi method to reach consensus on best
      practice recommendations for alemtuzumab infusion in MS patients. This valuable
      clinical resource provides a practical guide for clinicians to optimize patient
      education and implement strategies for infusion-associated reaction prophylaxis
      and management when administering alemtuzumab. 

PMID- 26295503
TI  - Clinical Significance of Arterial Stiffness and Thickness Biomarkers in Type 2
      Diabetes Mellitus: An Up-To-Date Meta-Analysis.
AB  - BACKGROUND: Type 2 Diabetes mellitus (T2DM) is associated with increased risk of
      cardiovascular disease (CVD). Previous studies explored the association of T2DM
      with arterial stiffness and thickness biomarkers including the augmentation index
      (AIX), aortic pulse wave velocity (aPWV), brachial-ankle PWV (baPWV), carotid
      intima-media wall thickness (IMT) as well as blood pressure (BP), low density
      lipoprotein cholesterol (LDL-C); however the conclusions are either inconsistent
      or incomprehensive. MATERIAL AND METHODS: The average differences of each
      included trial were expressed as the standardized mean difference (SMD) with 95%
      confidence interval (CI). Analyses of carotid IMT, aPWV, baPWV and AIX Systolic
      BP (SBP), diastolic BP (DBP), LDL-C and HDL-C were independently performed.
      Furthermore, subgroup analyses by ethnicity (Caucasian or Asian) were conducted.
      Begg's and Egger's tests were performed for potential publication biases
      detection. RESULTS: A total of 14 case-control eligible studies with 1222 T2DM
      patients and 1094 control subjects were included. In the overall analysis,
      significant associations were observed between the carotid IMT, aPWV, baPWV, LDL
      C, HDL-C, SBP, and DBP with T2DM (IMT: p=1.1*10-12; aPWV: p=1.1*10-7; baPWV:
      p=1.8*10-33; LDL-C: p=3.1*10-8; HDL-C: p=6.1*10-18; SBP: p=3.9*10-21; DBP:
      p=4.8*10-5). No association was detected for AIX (p=0.09). Subgroup analyses
      indicated that aPWV, baPWV, SBP, LDL-C, and HDL-C were associated with T2DM in
      both white and Asian populations (p<0.05). The significant associations of IMT,
      AIX and DBP with T2DM were only observed in the Asian subgroup. CONCLUSIONS:
      Carotid IMT, aPWV, baPWV, as well as LDL-C, HDL-C, SBP, and DBP but not AIX were
      useful noninvasive early markers for T2DM vascular dysfunction detection.

PMID- 26295505
TI  - Global Health and the Millennium Development Goals.

PMID- 26295504
TI  - Phosphine-Mediated Iterative Arene Homologation Using Allenes.
AB  - A PPh3-mediated multicomponent reaction between o-phthalaldehydes, nucleophiles,
      and monosubstituted allenes furnishes functionalized non-C2-symmetric
      naphthalenes in synthetically useful yields. When the o-phthalaldehydes were
      reacted with 1,3-disubstituted allenes in the presence of PPh2Et, naphthalene
      derivatives were also obtained in up to quantitative yields. The mechanism of the
      latter transformation is straightforward: aldol addition followed by Wittig
      olefination and dehydration. The mechanism of the former is a tandem gamma
      umpolung/aldol/Wittig/dehydration process, as established by preparation of
      putative reaction intermediates and mass spectrometric analysis. This
      transformation can be applied iteratively to prepare anthracenes and tetracenes
      using carboxylic acids as pronucleophiles. 

PMID- 26295506
TI  - Preterm Births: A Global Health Problem.
AB  - Globally, in 2012, there were 15 million babies born preterm. The majority of
      preterm births occur in resource-poor countries including India, Nigeria,
      Pakistan, and the Democratic Republic of Congo where many die due to lack of
      basic skilled nursing care. In September 2000, the United Nations signed the
      Millennium Development Declaration establishing eight Millennium Development
      Goals (MDGs). These MDGs provide specific, measurable targets that are designed
      to provide equitable health to all, particularly the most vulnerable including
      preterm babies. On May 2, 2014, the World Health Organization specifically
      targeted the nursing workforce as a key stakeholder in strategies to reduce
      global prematurity and end preventable preterm newborn deaths. Specific
      strategies include primary care, screening for risk factors, kangaroo mother
      care, and early initiation of breastfeeding with exclusive breastfeeding for the
      first 6 months of life. By sharing our knowledge and skills, nurses can
      contribute to global actions being taken to end preventable preterm newborn
      deaths. 

PMID- 26295507
TI  - Hydrocortisone Cream to Reduce Perineal Pain after Vaginal Birth: A Randomized
      Controlled Trial.
AB  - PURPOSE: To determine if the use of hydrocortisone cream decreases perineal pain
      in the immediate postpartum period. STUDY DESIGN AND METHODS: This was a
      randomized controlled trial (RCT), crossover study design, with each participant
      serving as their own control. Participants received three different methods for
      perineal pain management at three sequential perineal pain treatments after
      birth: two topical creams (corticosteroid; placebo) and a control treatment (no
      cream application). Treatment order was randomly assigned, with participants and
      investigators blinded to cream type. The primary dependent variable was the
      change in perineal pain levels (posttest minus pretest pain levels) immediately
      before and 30 to 60 minutes after perineal pain treatments. Data were analyzed
      with analysis of variance, with p < 0.05 considered significant. RESULTS: A total
      of 27 participants completed all three perineal pain treatments over a 12-hour
      period. A reduction in pain was found after application of both the topical
      creams, with average perineal pain change scores of -4.8 +/- 8.4 mm after
      treatment with hydrocortisone cream (N = 27) and -6.7 +/- 13.0 mm after treatment
      with the placebo cream (N = 27). Changes in pain scores with no cream application
      were 1.2 +/- 10.5 mm (N = 27). Analysis of variance found a significant
      difference between treatment groups (F2,89 = 3.6, p = 0.03), with both cream
      treatments having significantly better pain reduction than the control, no cream
      treatment (hydrocortisone vs. no cream, p = 0.04; placebo cream vs. no cream, p =
      0.01). There were no differences in perineal pain reduction between the two cream
      treatments (p = .54). CLINICAL IMPLICATIONS: This RCT found that the application
      of either hydrocortisone cream or placebo cream provided significantly better
      pain relief than no cream application.

PMID- 26295508
TI  - Breastfeeding and Childhood Obesity Among African Americans: A Systematic Review.
AB  - PURPOSE: Among African Americans, breastfeeding rates are lower and obesity rates
      higher than other ethnicities in the United States. The objective of this
      systematic review was to examine the correlation between breastfeeding practices
      and childhood obesity rates among African Americans in the United States. STUDY
      DATA SOURCE AND ELIGIBILITY CRITERIA: The Cumulative Index to Nursing and Allied
      Health Literature (CINAHL), PubMed, and Google Scholar were searched using the
      key words African Americans OR Blacks, Breastfeeding, Childhood Obesity OR
      Overweight, and Adolescent Obesity OR Overweight. Twelve articles met inclusion
      criteria and are discussed. RESULTS: No randomized-controlled trials or meta
      analyses were found. All studies were observational only. Eight studies found a
      protective effect of breastfeeding against childhood obesity among African
      Americans, whereas four other studies were inconclusive. LIMITATIONS: Only 12
      studies met inclusion criteria for this review, and all studies included other
      ethnicities in addition to African Americans. More evidence is needed to
      effectively generalize the results to this population. CONCLUSIONS AND
      IMPLICATIONS: More research is needed on the topic; however, current research
      does suggest a protective effect of breastfeeding against childhood obesity in
      this high-risk population. Primary care providers and other healthcare workers
      need to address breastfeeding benefits and barriers among African American women
      across the continuum of care.

PMID- 26295510
TI  - Antimicrobial Susceptibility Testing in Group B Streptococcus-Positive,
      Penicillin-Allergic Women.

PMID- 26295509
TI  - Relational Care for Perinatal Substance Use: A Systematic Review.
AB  - OBJECTIVE: The purpose of this systematic review of the literature is to
      highlight published studies of perinatal substance use disorder that address
      relational aspects of various care delivery models to identify opportunities for
      future studies in this area. METHOD: Quantitative, qualitative, and mixed-methods
      studies that included relational variables, such as healthcare provider
      engagement with pregnant women and facilitation of maternal-infant bonding, were
      identified using PubMed, Scopus, and EBSCO databases. Key words included neonatal
      abstinence syndrome, drug, opioid, substance, dependence, and pregnancy. RESULTS:
      Six studies included in this review identified statistically and/or clinically
      significant positive maternal and neonatal outcomes thought to be linked to
      engagement in antenatal care and development of caring relationships with
      healthcare providers. IMPLICATIONS/CONCLUSION: Comprehensive, integrated
      multidisciplinary services for pregnant women with substance use disorder aimed
      at harm reduction are showing positive results. Evidence exists that pregnant
      women's engagement with comprehensive services facilitated by caring
      relationships with healthcare providers may improve perinatal outcomes. Gaps in
      the literature remain; studies have yet to identify the relative contribution of
      multiple risk factors to adverse outcomes as well as program components most
      likely to improve outcomes.

PMID- 26295512
TI  - Implications of Excessive Gestational Weight Gain.

PMID- 26295511
TI  - Rejecting Standard Care: Vitamin K Prophylaxis for Newborns and Parent Choice.

PMID- 26295513
TI  - Robotic Journalism and Nursing.

PMID- 26295514
TI  - Empowering Sudanese Women and Promoting Their Health and Well-Being: The Courage
      and Commitment of One Woman.

PMID- 26295516
TI  - Safe Care for Maternal Substance Use and Neonatal Drug Withdrawal.

PMID- 26295519
TI  - Strontium biokinetic model for the lactating woman and transfer to breast milk:
      application to Techa River studies.
AB  - This paper presents a biokinetic model for strontium metabolism in the lactating
      woman and transfer to breast milk for members of Techa River communities exposed
      as a result of discharges of liquid radioactive wastes from the Mayak plutonium
      production facility (Russia) in the early 1950s. This model was based on that
      developed for the International Commission for Radiological Protection with
      modifications to account for population specific features of breastfeeding and
      maternal bone mineral metabolism. The model is based on a biokinetic model for
      the adult female with allowances made for changes in mineral metabolism during
      periods of exclusive and partial breast-feeding. The model for females of all
      ages was developed earlier from extensive data on (90)Sr-body measurements for
      Techa Riverside residents. Measurements of (90)Sr concentrations in the maternal
      skeleton and breast milk obtained in the1960s during monitoring of global fallout
      in the Southern Urals region were used for evaluation of strontium transfer to
      breast and breast milk. The model was validated with independent data from
      studies of global fallout in Canada and measurements of (90)Sr body-burden in
      women living in the Techa River villages who were breastfeeding during maximum
      (90)Sr-dietary intakes. The model will be used in evaluations of the intake of
      strontium radioisotopes in breast milk by children born in Techa River villages
      during the radioactive releases and quantification of (90)Sr retention in the
      maternal skeleton. 

PMID- 26295520
TI  - Observation of Triplet Exciton Formation in a Platinum-Sensitized Organic
      Photovoltaic Device.
AB  - Organic photovoltaics (OPVs) constitute a promising new technology due to their
      low production costs. However, OPV efficiencies remain low because excitons
      typically diffuse only ~5-20 nm during their lifetime, limiting the effective
      thickness of the light-absorbing layer. One strategy to improve OPVs is to
      increase exciton lifetimes by converting them into triplet states, which
      typically persist 10(3)-10(5) times longer than singlet excitons. We present
      femtosecond transient absorption and steady-state photovoltaic measurements of a
      model OPV system consisting of diphenyltetracene (DPT) films doped with platinum
      tetraphenylbenzoporphyrin (Pt(TPBP)). Photoexcitation of Pt(TPBP) creates a
      singlet excitation that rapidly intersystem crosses to a triplet state before
      transferring to the DPT host matrix. This transfer is rapid and efficient,
      occurring in 35 ps with an 85% conversion ratio of porphyrin singlets to DPT
      triplets. These triplet excitons lead to enhanced photocurrent response that
      increases with device thickness. 

PMID- 26295521
TI  - Site-Dependent Coordination Bonding in Self-Assembled Metal-Organic Networks.
AB  - The combination of organic linkers with metal atoms on top of inorganic
      substrates offers promising perspectives for functional electronic and magnetic
      nanoscale devices. Typically, coordination bonds between electron-rich end groups
      and transition-metal atoms lead to the self-assembly of metal-organic
      nanostructures, whose shape and electronic and magnetic properties crucially
      depend on the type of ligand. Here, we report on the site-selective bonding
      properties of Co atoms to the dichotomic dicyanoazobenzene molecule with its
      carbonitrile and diazo N-based moieties as possible ligands. Using low
      temperature scanning tunneling microscopy (STM) and spectroscopy measurements, we
      resolve the formation of self-assembled metal-organic motifs. Cobalt atoms
      exhibit a clear spectroscopic fingerprint dependent on the different coordination
      site, which is further used to map their position, otherwise not clearly visible
      in the topographic STM images. Density functional theory corroborates the
      observed bonding patterns and evidences their coordinative nature. 

PMID- 26295522
TI  - Atomic-Resolution Kinked Structure of an Alkylporphyrin on Highly Ordered
      Pyrolytic Graphite.
AB  - The atomic structure of the chains of an alkyl porphyrin (5,10,15,20
      tetranonadecylporphyrin) self-assembled monolayer (SAM) at the solid/liquid
      interface of highly ordered pyrolytic graphite (HOPG) and 1-phenyloctane is
      resolved using calibrated scanning tunneling microscopy (STM), density functional
      theory (DFT) image simulations, and ONIOM-based geometry optimizations. While
      atomic structures are often readily determined for porphyrin SAMs, the
      determination of the structure of alkyl-chain connections has not previously been
      possible. A graphical calibration procedure is introduced, allowing accurate
      observation of SAM lattice parameters, and, of the many possible atomic
      structures modeled, only the lowest-energy structure obtained was found to
      predict the observed lattice parameters and image topography. Hydrogen atoms are
      shown to provide the conduit for the tunneling current through the alkyl chains. 

PMID- 26295523
TI  - Enhanced Oxygen Reduction Activity of Platinum Monolayer on Gold Nanoparticles.
AB  - The increase in oxygen binding energy was previously proposed to account for the
      lower oxygen reduction activity of a Pt monolayer supported on Au(111) single
      crystal than that on Pd(111) and pure Pt(111) surfaces. This single-crystal based
      understanding, however, cannot explain the new finding of a 1.6-fold increase of
      oxygen reduction activity on Pt monolayer-modified 3-nm Au nanoparticles
      (Pt/Au/C) in comparison with that on Pt/Pd/C with a similar particle size. The
      Pt/Au/C catalyst also has an activity higher than that of a state-of-the-art 2.8
      nm Pt/C catalyst. Our new experimental results and density functional theory
      calculations demonstrate that a significant compressive strain in the surface of
      the core nanoparticles plays a role in the observed activity enhancement. 

PMID- 26295524
TI  - Electronic Functionality in Graphene-Based Nanoarchitectures: Discovery and
      Design via First-Principles Modeling.
AB  - Graphene has promised many novel applications in nanoscale electronics and
      sustainable energy due to its novel electronic properties. Computational
      exploration of electronic functionality and how it varies with architecture and
      doping presently runs ahead of experimental synthesis yet provides insights into
      types of structures that may prove profitable for targeted experimental synthesis
      and characterization. We present here a summary of our understanding on the
      important aspects of dimension, band gap, defect, and interfacial engineering of
      graphene based on state-of-the-art ab initio approaches. Some most recent
      experimental achievements relevant for future theoretical exploration are also
      covered. 

PMID- 26295525
TI  - Infrared Spectrum of the Hydrated Proton in Water.
AB  - Reactive molecular dynamics simulations have been utilized to calculate the
      infrared (IR) spectra of acidic HCl solutions of varying concentration with the
      goal of achieving a better understanding of the spectral features of the hydrated
      excess protons in bulk water. To incorporate the essential physics of the
      hydrated proton, we carried out the simulations using the specialized self
      consistent iterative multistate empirical valence bond (SCI-MS-EVB) method, which
      is a form of multiconfigurational (reactive) molecular dynamics. After the pure
      water absorption background was removed, the calculated difference spectra are in
      good agreement with prior experimental results. The continuous broad absorption
      band in the acidic IR spectrum is, for the first time, interpreted based on the
      concept of a dynamically distorted Eigen cation, H9O4(+), which has been shown to
      provide the most accurate description for the charge defect character of the
      hydrated excess proton in liquid water. 

PMID- 26295526
TI  - The Eighth Bacteriochlorophyll Completes the Excitation Energy Funnel in the FMO
      Protein.
AB  - The Fenna-Matthews-Olson (FMO) light-harvesting protein connects the outer
      antenna system (chlorosome/baseplate) with the reaction center complex in green
      sulfur bacteria. Since its first structure determination in the mid-70s, this
      pigment-protein complex has become an important model system to study excitation
      energy transfer. Recently, an additional bacteriochlorophyll a (the eighth)
      pigment was discovered in each subunit of this homotrimer. Our structure-based
      calculations of the optical properties of the FMO protein demonstrate that the
      eighth pigment is the linker to the baseplate, confirming recent suggestions from
      crystallographic studies. 

PMID- 26295527
TI  - Electronic Structure of Ligand-Passivated Gold and Silver Nanoclusters.
AB  - Gold and silver nanoclusters have unique molecule-like electronic structure and a
      nonzero HOMO-LUMO gap. Recent advances in X-ray crystal structure determination
      have led to a new understanding of the geometric structure of gold nanoparticles,
      with significant implications for electronic structure. The superatom model has
      been effectively employed to explain properties such as one- and two-photon
      optical absorption, circular dichroism, EPR spectra, and electronic effects
      introduced by nanoparticle doping. Future investigations may also lead to an
      understanding of nanoparticle luminescence, excited-state dynamics, and the
      metallic to molecular transition. 

PMID- 26295528
TI  - New Insights into the Structure of the Vapor/Water Interface from Large-Scale
      First-Principles Simulations.
AB  - We present extensive ab initio simulations of the molecular arrangements at the
      vapor/water interface, which provide valuable insights into the interface
      structure. In particular, the simulations address the controversy of whether
      there is a significant amount of nondonor configurations at this prototypical
      interface, using a novel Car-Parrinello-like ab initio molecular dynamics
      approach. The interface is modeled by a system of 384 water molecules for 125 ps
      in a two-dimensional periodic slab, the most extensive ab initio molecular
      dynamics simulation to date. In contrast to previous theoretical simulations and
      X-ray absorption spectroscopy, but consistent with sum-frequency generation
      experiments, we observe no evidence for a significant occurrence of acceptor-only
      species at the vapor/water interface. Besides a distinct surface relaxation
      effect, we find that only the topmost layers of the interface obey structural
      order. 

PMID- 26295529
TI  - Strong and Long Makes Short: Strong-Pump Strong-Probe Spectroscopy.
AB  - We propose a new time-domain spectroscopic technique that is based on strong pump
      and probe pulses. The strong-pump strong-probe (SPSP) technique provides temporal
      resolution that is not limited by the durations of the pump and probe pulses. By
      numerically exact simulations of SPSP signals for a multilevel vibronic model, we
      show that the SPSP signals exhibit electronic and vibrational beatings on time
      scales which are significantly shorter than the pulse durations. This suggests
      the possible application of SPSP spectroscopy for the real-time investigation of
      molecular processes that cannot be temporally resolved by pump-probe spectroscopy
      with weak pump and probe pulses. 

PMID- 26295530
TI  - Assessing the Solvation Numbers of Electrolytic Ions Confined in Carbon Nanopores
      under Dynamic Charging Conditions.
AB  - We propose herein a new reliable approach to assess solvation numbers of ions
      confined in carbon nanopores based on dynamic quartz crystal measurements. This
      was proved for the entire families of alkaline, alkaline-earth cations, and
      halogen anions. As-assessed hydration numbers appear in the sequence
      characteristic of a transition from the cosmotropic to a chaotropic-type behavior
      with the decrease of the ion's charge-to-size ratio. The information on the
      behavior of ions confined in nanometric space of different (especially charged)
      carbon materials is in high demand for the development of powerful
      supercapacitors, nanofiltration membranes, and chemical/biochemical sensors. 

PMID- 26295531
TI  - Computational Nanomaterials Modeling.

PMID- 26295533
TI  - Interaction of blood components with cathelicidins and their modified versions.
AB  - Cationic antimicrobial peptides (cAMPs) serve as effective components of the
      innate host defense against microbial infections. cAMPs often show broad-spectrum
      antimicrobial activity, but narrow-band activity is also observed. Despite their
      great potential, the polycationic nature of cAMPs could cause serious side
      effects once in the bloodstream which may limit their applications. However,
      there is very limited knowledge available on AMPs interaction with blood
      components in spite of the fact that the most likely route of administration to
      treat systemic microbial infections for these peptides is intravenous, where they
      immediately come in contact with all blood components. In order to evaluate the
      therapeutic potential of cAMPs as new alternative to antibiotics, we investigated
      the impact of cathelicidin related cAMPs on red blood cell lysis, aggregation,
      platelet activation, blood coagulation, and complement activation. The influence
      of cAMPs on blood depends on hydrophobicity and number of charges in the
      peptides. The hemolytic activity of cathelicidin (bactenecin) variants was much
      less than that of indolicidin due to their lower hydrophobicity. Except
      indolicidin, none of the peptides induce platelet activation. Some of bactenecin
      variants (R3, Sub3 and W3) with higher charge inhibited the blood coagulation.
      The cAMPs did not activate or inhibit complement at the concentrations studied,
      expect for the peptide (Sub3). Our data shows that it is important to investigate
      cAMP-based drug candidates regarding their interaction with blood components
      early on in the development process. We anticipate that this new knowledge on
      blood interaction of antimicrobial peptides will help to design peptides with a
      better therapeutic window and with less side effects. 

PMID- 26295532
TI  - TALEN-mediated functional correction of X-linked chronic granulomatous disease in
      patient-derived induced pluripotent stem cells.
AB  - X-linked chronic granulomatous disease (X-CGD) is an inherited disorder of the
      immune system. It is characterized by a defect in the production of reactive
      oxygen species (ROS) in phagocytic cells due to mutations in the NOX2 locus,
      which encodes gp91phox. Because the success of retroviral gene therapy for X-CGD
      has been hampered by insertional activation of proto-oncogenes, targeting the
      insertion of a gp91phox transgene into potential safe harbor sites, such as
      AAVS1, may represent a valid alternative. To conceptually evaluate this strategy,
      we generated X-CGD patient-derived induced pluripotent stem cells (iPSCs), which
      recapitulate the cellular disease phenotype upon granulocytic differentiation. We
      examined AAVS1-specific zinc-finger nucleases (ZFNs) and transcription activator
      like effector nucleases (TALENs) for their efficacy to target the insertion of a
      myelo-specific gp91phox cassette to AAVS1. Probably due to their lower
      cytotoxicity, TALENs were more efficient than ZFNs in generating correctly
      targeted iPSC colonies, but all corrected iPSC clones showed no signs of
      mutations at the top-ten predicted off-target sites of both nucleases. Upon
      differentiation of the corrected X-CGD iPSCs, gp91phox mRNA levels were highly up
      regulated and the derived granulocytes exhibited restored ROS production that
      induced neutrophil extracellular trap (NET) formation. In conclusion, we
      demonstrate that TALEN-mediated integration of a myelo-specific gp91phox
      transgene into AAVS1 of patient-derived iPSCs represents a safe and efficient way
      to generate autologous, functionally corrected granulocytes. 

PMID- 26295534
TI  - Communicating Potential Radiation-Induced Cancer Risks From Medical Imaging
      Directly to Patients.
AB  - OBJECTIVE: Over the past decade, efforts have increasingly been made to decrease
      radiation dose from medical imaging. However, there remain varied opinions about
      whether, for whom, by whom, and how these potential risks should be discussed
      with patients. We aimed to provide a review of the literature regarding awareness
      and communication of potential radiation-induced cancer risks from medical
      imaging procedures in hopes of providing guidance for communicating these
      potential risks with patients. MATERIALS AND METHODS: We performed a systematic
      literature review on the topics of radiation dose and radiation-induced cancer
      risk awareness, informed consent regarding radiation dose, and communication of
      radiation-induced cancer risks with patients undergoing medical imaging. We
      included original research articles from North America and Europe published
      between 1995 and 2014. RESULTS: From more than 1200 identified references, a
      total of 22 original research articles met our inclusion criteria. Overall, we
      found that there is insufficient knowledge regarding radiation-induced cancer
      risks and the magnitude of radiation dose associated with CT examinations among
      patients and physicians. Moreover, there is minimal sharing of information before
      nonacute imaging studies between patients and physicians about potential long
      term radiation risks. CONCLUSION: Despite growing concerns regarding medical
      radiation exposure, there is still limited awareness of radiation-induced cancer
      risks among patients and physicians. There is also no consensus regarding who
      should provide patients with relevant information, as well as in what specific
      situations and exactly what information should be communicated. Radiologists
      should prioritize development of consensus statements and novel educational
      initiatives with regard to radiation-induced cancer risk awareness and
      communication.

PMID- 26295535
TI  - Nuclear Reactor Accident Fallout Artifacts: Unusual Black Spots on Digital
      Radiographs.
AB  - OBJECTIVE: The Fukushima nuclear power plant accident resulted in the discharge
      of radioactive particulate material into the atmosphere. Consequently, several
      hospitals in Japan have observed black spots on x-ray computed radiography (CR)
      images caused by particulate radioactive fallout. CONCLUSION: These black spots
      have no effect on human health. To reduce the influence of black spots on CR
      images, we need to erase latent images on imaging plates (IPs) immediately before
      clinical use and read the IPs soon after the x-ray examination. Alternatively,
      the contaminated felt of a cassette can be cleaned or exchanged, if possible.

PMID- 26295536
TI  - Periimplant Breast Gas at High Altitudes: Prevalence, Significance, and Possible
      Associated Factors.
AB  - OBJECTIVE: The objective of our study was to confirm the suspected incidental
      nature of periimplant gas and characterize possible predisposing factors.
      MATERIALS AND METHODS: Three hundred twenty-one chest CT examinations of patients
      with breast implants over a 2-year period were identified using a research
      database query. Scans were evaluated for the qualitative presence of gas, the
      implant type, and the presence of implant rupture, capsular calcifications, and
      axillary clips. Subjects' self-reported home state address was included as a
      surrogate for recent airline travel or travel from lower altitudes to our center
      located in Denver, CO, which is 1 mile (1.6 km) above sea level. RESULTS: Of the
      321 study subjects, 55 (17.1%) had periimplant gas present. No subject had CT
      signs or clinical evidence of chest wall infection. Periimplant breast gas was
      significantly associated with residence outside Colorado (odds ratio [OR], 28.32;
      95% CI, 10.60-75.70), silicone implant type (OR, 14.56; 95% CI, 5.61-37.81), and
      implant rupture (OR, 4.21; 95% CI, 1.74-10.18). Capsular calcifications were
      associated with gas in backward elimination analysis only (OR, 2.15; 95% CI, 1.03
      4.50). No association was found between periimplant gas and implant location,
      patient age, or the presence of axillary clips. CONCLUSION: Periimplant breast
      gas was relatively common in our patient population, and no association with
      infection was found. Our results suggest that the development of gas is related
      to atmospheric pressure, implant filler, and implant integrity. Gas around breast
      implants after airline travel or an altitude change can be safely dismissed in
      the absence of other associated findings.

PMID- 26295537
TI  - An Alternative Technique for the Fabrication of a Metal-Reinforced Interim
      Implant-Supported Fixed Prosthesis: A Clinical Report.
AB  - Despite advancements in restorative materials and techniques, complications with
      implant-supported fixed prostheses such as veneer fracture and material wear are
      very common and present with varying frequencies. Following these complications,
      repair of this type of prosthesis can be time-consuming and costly even in the
      hand of experience clinicians. Several techniques have proposed using the
      existing framework to minimize the cost of the repair for the patient; however,
      while the repairs are being performed, the patient will have to either wear an
      interim complete denture or no prosthesis, which might cause some inconvenience
      to the patient. This article will present a technique for the fabrication of a
      metal-reinforced interim implant-supported fixed prosthesis for patients to wear
      while the existing prosthesis is being repaired.

PMID- 26295538
TI  - Photolysis of three antiviral drugs acyclovir, zidovudine and lamivudine in
      surface freshwater and seawater.
AB  - Photodegradation is an important elimination process for many pharmaceuticals in
      surface waters. In this study, photodegradation of three antiviral drugs,
      acyclovir, zidovudine, and lamivudine, was investigated in pure water,
      freshwater, and seawater under the irradiation of simulated sunlight. Results
      showed that zidovudine was easily transformed via direct photolysis, while
      acyclovir and lamivudine were mainly transformed via indirect photolysis. We
      found that in freshwater, nitrate enhanced the photodegradation of the three
      antiviral drugs, bicarbonate promoted the photodegradation of acyclovir, and
      dissolved organic matter (DOM) accelerated the photolysis of acyclovir and
      lamivudine. In seawater, the photolysis of acyclovir was not susceptible to Cl(
      ), Br(-) and ionic strength; however, the photolysis of zidovudine was inhibited
      by Cl(-) and Br(-), and the photolysis of lamivudine was enhanced by Cl(-), Br(-)
      and ionic strength. Second-order reaction rate constants for the three antiviral
      drugs with (1)O2 (k1O2) and OH (kOH) were also measured. These results are
      important for fate and ecological risk assessment of the antiviral drugs in
      natural waters. 

PMID- 26295539
TI  - Formation of hydroxylated polybrominated diphenyl ethers from laccase-catalyzed
      oxidation of bromophenols.
AB  - Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) have been frequently found
      in the marine biosphere as emerging organic contaminants. Studies to date have
      suggested that OH-PBDEs in marine biota are natural products. However, the
      mechanisms leading to the biogenesis of OH-PBDEs are still far from clear. In
      this study, using a laccase isolated from Trametes versicolor as the model
      enzyme, we explored the formation of OH-PBDEs from the laccase-catalyzed
      oxidation of simple bromophenols (e.g., 2,4-DBP and 2,4,6-TBP). Experiments under
      ambient conditions clearly showed that OH-PBDEs were produced from 2,4-DBP and
      2,4,6-TBP in presence of laccase. Polybrominated compounds 2'-OH-BDE68, 2,2'-diOH
      BB80, and 1,3,8-TrBDD were identified as the products from 2,4-DBP, and 2'-OH
      BDE121 and 4'-OH-BDE121 from 2,4,6-TBP. The production of OH-PBDEs was likely a
      result of the coupling of bromophenoxy radicals, generated from the laccase
      catalyzed oxidation of 2,4-DBP or 2,4,6-TBP. The transformation of bromophenols
      by laccase was pH-dependant, and was also influenced by enzymatic activity. In
      view of the abundance of 2,4-DBP and 2,4,6-TBP and the phylogenetic distribution
      of laccases in the environment, laccase-catalyzed conversion of bromophenols may
      be potentially an important route for the natural biosynthesis of OH-PBDEs. 

PMID- 26295540
TI  - Exploring potential contributors to endocrine disrupting activities in Taiwan's
      surface waters using yeast assays and chemical analysis.
AB  - Surface waters serve as sinks for anthropogenic contaminants, including naturally
      occurring hormones and a variety of synthetic endocrine active substances. To
      investigate the presence of endocrine active contaminants in the aquatic
      environment in Taiwan, river water and suspended solids were analyzed by yeast
      assays to examine the distribution of estrogenic, androgenic, and aryl
      hydrocarbon receptor agonist activities. The results showed that dry-season river
      samples exhibited strong estrogenic and aryl hydrocarbon receptor agonist
      activities, but no androgenic activity was detected. Owing to the ubiquitous
      detection of estrogenic activities in Taiwan's surface waters, samples were
      further subjected to liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      analysis for quantification of selected estrogenic compounds. LC-MS/MS results
      indicated that natural estrogens, such as estrone and 17beta-estradiol were often
      the most contributing compounds for the bioassay-derived estrogenic activities
      due to their strong estrogenic potencies and high detection frequencies, whereas
      high concentrations of bisphenol A and nonylphenol also posed a threat to the
      aquatic ecosystems in Taiwan. Water samples eliciting strong estrogenic
      activities were further fractionated using high performance liquid
      chromatography, and significant estrogenic activities were detected in fractions
      containing estrone, 17beta-estradiol, 17alpha-ethynylestradiol, and bisphenol A.
      Also, the presence of unidentified estrogenic compounds was found in few river
      water samples. Further identification of unknown endocrine active substances is
      necessary to better protect the aquatic environment in Taiwan. 

PMID- 26295541
TI  - Spontaneous aggregation of humic acid observed with AFM at different pH.
AB  - Atomic force microscopy in contact (AFM-C) mode was used to investigate the
      molecular dynamics of leonardite humic acid (HA) aggregate formed at different pH
      values. HA nanoparticles dispersed at pH values ranging from 2 to 12 were
      observed on a mica surface under dry conditions. The most clearly resolved and
      well-resulted AFM images of single particle were obtained at pH 5, where HA
      appeared as supramolecular particles with a conic shape and a hole in the centre.
      Those observations suggested that HA formed under these conditions exhibited a
      pseudo-amphiphilic nature, with secluded hydrophobic domains and polar subunits
      in direct contact with hydrophilic mica surface. Based on molecular simulation
      methods, a lignin-carbohydrate complex (LCC) model was proposed to explain the HA
      ring-like morphology. The LCC model optimized the parameters of beta-O-4 linkages
      between 14 units of 1-4 phenyl propanoid, and resulted in an optimized structure
      comprising 45-50 linear helical molecules looped spirally around a central
      cavity. Those results added new insights on the adsorption mechanism of HA on
      polar surfaces as a function of pH, which was relevant from the point of view of
      natural aggregation in soil environment. 

PMID- 26295542
TI  - Modeling and predicting pKa values of mono-hydroxylated polychlorinated biphenyls
      (HO-PCBs) and polybrominated diphenyl ethers (HO-PBDEs) by local molecular
      descriptors.
AB  - Hydroxylated polychlorinated biphenyls (HO-PCBs) and polybrominated diphenyl
      ethers (HO-PBDEs) are attracting considerable concerns because of their multiple
      endocrine-disrupting effects and wide existence in environment and organisms. The
      hydroxyl groups enable these chemicals to be ionizable, and dissociation
      constant, pKa, becomes an important parameter for investigating their
      environmental behavior and biological activities. In this study, a new pKa
      prediction model was developed using local molecular descriptors. The dataset
      contains 21 experimental pKa values of HO-PCBs and HO-PBDEs. The optimized
      geometries by ab initio HF/6-31G(**) algorithm were used to calculate the site
      specific molecular readiness to accept or donate electron charges. The developed
      model obtained good statistical performance, which significantly outperformed
      commercial software ACD and SPARC. Mechanism analysis indicates that pKa values
      increase with the charge-limited donor energy EQocc on hydroxyl oxygen atom and
      decrease with the energy-limited acceptor charge QEvac on hydroxyl hydrogen atom.
      The regression model was also applied to calculate pKa values for all 837 mono
      hydroxylated PCBs and PBDEs in each class, aiming to provide basic data for the
      ecological risk assessment of these chemicals. 

PMID- 26295545
TI  - A question of wellness: it's time to find some answers.

PMID- 26295546
TI  - DEVASTATING FLU, ONGOING HARM.

PMID- 26295547
TI  - Constraints on nonclinical career options.

PMID- 26295543
TI  - SSEA-4 and YKL-40 positive progenitor subtypes in the subventricular zone of
      developing human neocortex.
AB  - The glycosphingolipid SSEA-4 and the glycoprotein YKL-40 have both been
      associated with human embryonic and neural stem cell differentiation. We
      investigated the distribution of SSEA-4 and YKL-40 positive cells in
      proliferative zones of human fetal forebrain using immunohistochemistry and
      double-labeling immunofluorescence. A few small rounded SSEA-4 and YKL-40 labeled
      cells were present in the radial glial BLBP positive proliferative zones adjacent
      to the lateral ganglionic eminence from 12th week post conception. With
      increasing age, a similarly stained cell population appeared more widespread in
      the subventricular zone. At midgestation, the entire subventricular zone showed
      patches of SSEA-4, YKL-40, and BLBP positive cells. Co-labeling with markers for
      radial glial cells (RGCs) and neuronal, glial, and microglial markers tested the
      lineage identity of this subpopulation of radial glial descendants. Adjacent to
      the ventricular zone, a minor fraction showed overlap with GFAP but not with
      nestin, Olig2, NG2, or S100. No co-localization was found with neuronal markers
      NeuN, calbindin, DCX or with markers for microglial cells (Iba-1, CD68).
      Moreover, the SSEA-4 and YKL-40 positive cell population in subventricular zone
      was largely devoid of Tbr2, a marker for intermediate neuronal progenitor cells
      descending from RGCs. YKL-40 has recently been found in astrocytes in the neuron
      free fimbria, and both SSEA-4 and YKL-40 are present in malignant astroglial
      brain tumors. We suggest that the population of cells characterized by
      immunohistochemical combination of antibodies against SSEA-4 and YKL-40 and
      devoid of neuronal and microglial markers represent a yet unexplored astrogenic
      lineage illustrating the complexity of astroglial development.

PMID- 26295548
TI  - What Is Your Diagnosis? Mycosis leading to cranial mesenteric pseudoaneurysm and
      secondary intestinal perforation with septic peritonitis.

PMID- 26295549
TI  - What Is Your Diagnosis? Leiomyosarcoma.

PMID- 26295550
TI  - What Is Your Neurologic Diagnosis? Suspected immune-mediated thrombocytopenia
      with secondary spinal cord hemorrhage.

PMID- 26295551
TI  - ECG of the Month. Arrhythmogenic right ventricular cardiomyopathy.

PMID- 26295552
TI  - Anesthesia Case of the Month. Intrathoracic tracheal avulsion.

PMID- 26295553
TI  - Pathology in Practice. A equuli septicemia in a neonatal foal.

PMID- 26295554
TI  - Systematic evaluation of scientific research for clinical relevance and control
      of bias to improve clinical decision making.

PMID- 26295555
TI  - Evaluation of total dietary fiber concentration and composition of commercial
      diets used for management of diabetes mellitus, obesity, and dietary fat
      responsive disease in dogs.
AB  - OBJECTIVE: To determine total dietary fiber (TDF) concentration and composition
      of commercial diets used for management of obesity, diabetes mellitus, and
      dietary fat-responsive disease in dogs. DESIGN: Cross-sectional study. SAMPLE:
      Dry (n = 11) and canned (8) canine therapeutic diets. PROCEDURES: Insoluble and
      soluble dietary fiber (IDF and SDF), high-molecular-weight SDF (HMWSDF), and low
      molecular-weight SDF (LMWSDF) concentrations were determined. Variables were
      compared among diets categorized by product guide indication, formulation (dry vs
      canned), and regulatory criteria for light and low-fat diets. RESULTS: SDF
      (HMWSDF and LMWSDF) comprised a median of 30.4% (range, 9.4% to 53.7%) of TDF;
      LMWSDF contributed a median of 11.5% (range, 2.7% to 33.8%) of TDF. Diets for
      diabetes management had higher concentrations of IDF and TDF with lower
      proportions of SDF and LMWSDF contributing to TDF, compared with diets for
      treatment of fat-responsive disease. Fiber concentrations varied within diet
      categories and between canned and dry versions of the same diet (same name and
      manufacturer) for all pairs evaluated. Diets classified as light contained higher
      TDF and IDF concentrations than did non-light diets. All canned diets were
      classified as low fat, despite providing up to 38% of calories as fat.
      CONCLUSIONS AND CLINICAL RELEVANCE: Diets provided a range of TDF concentrations
      and compositions; veterinarians should request TDF data from manufacturers, if
      not otherwise available. Consistent responses to dry and canned versions of the
      same diet cannot necessarily be expected, and diets with the same indications may
      not perform similarly. Many diets may not provide adequate fat restriction for
      treatment of dietary fat-responsive disease.

PMID- 26295556
TI  - Comparison of foods with differing nutritional profiles for long-term management
      of acute nonobstructive idiopathic cystitis in cats.
AB  - OBJECTIVE: To evaluate the effect of nutrition on recurrent clinical signs of
      lower urinary tract (LUT) disease in cats with idiopathic cystitis. DESIGN:
      Randomized, controlled, masked clinical trial. ANIMALS: 31 cats with acute
      nonobstructive idiopathic cystitis. PROCEDURES: Cats were assigned to receive 1
      of 2 foods (a cystitis prevention or control food) that differed in mineral
      (calcium, phosphorous, and magnesium), antioxidant, and fatty acid profiles.
      Owners documented LUT signs daily for up to 1 year. The primary endpoint was the
      number of recurrent episodes in which a cat had multiple (>= 2 concurrent) LUT
      signs within a day (defined as multiple-sign day). Consecutive days in which a
      cat had multiple LUT signs were considered as a single episode. RESULTS: 4 cats
      fed prevention food and 2 cats fed control food were excluded from analysis
      because of noncompliance, gastrointestinal signs, food refusal, or owner
      voluntary withdrawal. The proportion of cats fed prevention food that had >= 1
      recurrent episode of multiple-sign days (4/11) was not significantly lower than
      that of cats fed control food (9/14). However, cats fed prevention food had
      significantly lower mean incidence rates for recurrent episodes of multiple-sign
      days (0.7 episodes/1,000 cat-days) and episodes of hematuria (0.3 episodes/1,000
      cat-days), dysuria (0.2 episodes/1,000 cat-days), and stranguria (0.2
      episodes/1,000 cat-days) as single LUT signs, compared with cats fed control food
      (5.4, 3.4, 3.1, and 3.8 episodes/1,000 cat-days, respectively). Significantly
      fewer cats fed prevention food required analgesics (4/11), compared with cats fed
      control food (12/14). CONCLUSIONS AND CLINICAL RELEVANCE: Foods with differing
      nutritional profiles appeared to impact mean incidence rates of recurrent feline
      idiopathic cystitis-associated signs.

PMID- 26295557
TI  - Respective associations between ureteral obstruction and renomegaly, urine
      specific gravity, and serum creatinine concentration in cats: 29 cases (2006
      2013).
AB  - OBJECTIVE: To determine the respective associations between ureteral obstruction
      and renomegaly, urine specific gravity (USG), and serum creatinine concentration
      and to assess the reliability of abdominal palpation for detection of renomegaly
      in cats. DESIGN: Retrospective case series. ANIMALS: 89 client-owned cats with (n
      = 29) or without ureteral obstruction and with (30) or without (30) kidney
      disease. PROCEDURES: Medical records of cats that underwent abdominal
      ultrasonography at a veterinary teaching hospital from January 2006 through April
      2013 were reviewed. Cats were categorized as having ureteral obstruction
      (obstructed group) or no ureteral obstruction with (KD group) or without kidney
      disease (NKD group). Renomegaly and renal asymmetry were defined on the basis of
      mean renal length for NKD cats. Prevalence of renomegaly and renal asymmetry,
      mean USG and serum creatinine concentration, and abdominal palpation and
      ultrasonographic findings were compared among the groups. RESULTS: Renomegaly was
      identified in 2 obstructed cats and 1 KD cat and was not associated with ureteral
      obstruction. Renal asymmetry was detected in 18 obstructed cats and 11 KD cats.
      For obstructed and KD cats, the mean USG was significantly lower and the mean
      serum creatinine concentration was significantly greater than those for NKD cats.
      Twenty-eight of 29 cats with ureteral obstruction had hypercreatininemia.
      Abdominal palpation was not a reliable method for detection of renomegaly.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated renomegaly was not
      associated with ureteral obstruction in cats, and abdominal palpation was an
      unreliable method for detection of renomegaly. The most consistent abnormal
      finding for cats with ureteral obstruction was hypercreatininemia.

PMID- 26295558
TI  - Correction: Comparison of peak flow velocity through the left ventricular outflow
      tract and effective orifice area indexed to body surface area in Golden Retriever
      puppies to predict development of subaortic stenosis in adult dogs.

PMID- 26295559
TI  - Salmonella bacteriuria in a cat fed a Salmonella-contaminated diet.
AB  - CASE DESCRIPTION: A 9-year-old castrated male domestic shorthair cat was
      evaluated because of hematuria and weight loss after an 8-year history of
      intermittent signs of feline lower urinary tract disease (FLUTD). A complete diet
      history revealed that the cat was eating a commercial diet that does not undergo
      the same processing procedures as most pet foods and so might be at increased
      risk for bacterial contamination owing to a nonstandard industry cooking
      procedure. CLINICAL FINDINGS: The cat had a history consistent with FLUTD, but
      bacteriologic culture of the urine revealed Salmonella organisms. Additional
      analysis revealed Salmonella enterica serotype I:ROUGH-O:g,m,s:- in samples of
      urine and feces as well as Salmonella enterica serotype Johannesburg and
      Salmonella enterica serotype Senftenberg in the diet. TREATMENT AND OUTCOME: The
      cat responded positively to antimicrobial treatment for the Salmonella
      bacteriuria as well as to dietary and environmental management for the clinical
      signs associated with FLUTD. CLINICAL RELEVANCE: Findings in this case
      highlighted an additional health consequence associated with ingestion of
      Salmonella-contaminated food. Such contamination is of particular concern with
      raw meat-based diets or diets that have not undergone standard industry cooking
      practices. Veterinarians should obtain a diet history for every companion animal
      during every evaluation to help with diagnosis and optimal treatment.

PMID- 26295560
TI  - Management of a pet dog after exposure to a human patient with Ebola virus
      disease.
AB  - In October 2014, a health-care worker who had been part of the treatment team for
      the first laboratory-confirmed case of Ebola virus disease imported to the United
      States developed symptoms of Ebola virus disease. A presumptive positive reverse
      transcription PCR assay result for Ebola virus RNA in a blood sample from the
      worker was confirmed by the CDC, making this the first documented occurrence of
      domestic transmission of Ebola virus in the United States. The Texas Department
      of State Health Services commissioner issued a control order requiring
      disinfection and decontamination of the health-care worker's residence. This
      process was delayed until the patient's pet dog (which, having been exposed to a
      human with Ebola virus disease, potentially posed a public health risk) was
      removed from the residence. This report describes the movement, quarantine, care,
      testing, and release of the pet dog, highlighting the interdisciplinary, one
      health approach and extensive collaboration and communication across local,
      county, state, and federal agencies involved in the response.

PMID- 26295561
TI  - On-site veterinary medical evaluation and care of working dogs and horses at the
      2012 Republican National Convention.
AB  - OBJECTIVE: To describe on-site veterinary medical care for working dogs and
      horses deployed for the 2012 Republican National Convention (RNC) in Tampa, Fla,
      August 24 to 30, 2012. DESIGN: Retrospective case series. SAMPLE: 130 dogs and 45
      horses. PROCEDURES: Data collected included breed, age, history, task assignment,
      reason for evaluation, and physical examination findings. A patient encounter
      report was recorded each time an animal was seen by veterinary staff for a
      physical evaluation. RESULTS: 46 of the 130 (35%) dogs and all 45 (100%) horses
      underwent at least 1 on-site veterinary evaluation, for a total of 478 patient
      encounters. The most common reason for an on-site veterinary evaluation was a
      wellness check (446 patient encounters). On the basis of veterinary
      recommendations, 1 dog and 4 horses were removed from continued service for the
      duration of the event. In addition, 1 dog and 1 horse were removed from active
      service for 12 to 24 hours but allowed to return to service for the duration of
      the event following a veterinary reevaluation. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggested that working dogs and horses deployed for large
      planned events face different health concerns, compared with concerns previously
      reported for animals deployed following disasters. Pre-event planning and
      training of handlers and riders may have helped reduce the number of health
      concerns, particularly health concerns related to high heat.

PMID- 26295562
TI  - Heritable alteration of DNA methylation induced by whole-chromosome aneuploidy in
      wheat.
AB  - Aneuploidy causes changes in gene expression and phenotypes in all organisms
      studied. A previous study in the model plant Arabidopsis thaliana showed that
      aneuploidy-generated phenotypic changes can be inherited to euploid progenies and
      implicated an epigenetic underpinning of the heritable variations. Based on an
      analysis by amplified fragment length polymorphism and methylation-sensitive
      amplified fragment length polymorphism markers, we found that although genetic
      changes at the nucleotide sequence level were negligible, extensive changes in
      cytosine DNA methylation patterns occurred in all studied homeologous group 1
      whole-chromosome aneuploid lines of common wheat (Triticum aestivum), with
      monosomic 1A showing the greatest amount of methylation changes. The changed
      methylation patterns were inherited by euploid progenies derived from the
      aneuploid parents. The aneuploidy-induced DNA methylation alterations and their
      heritability were verified at selected loci by bisulfite sequencing. Our data
      have provided empirical evidence supporting earlier suggestions that heritability
      of aneuploidy-generated, but aneuploidy-independent, phenotypic variations may
      have an epigenetic basis. That at least one type of aneuploidy - monosomic 1A -
      was able to cause significant epigenetic divergence of the aneuploid plants and
      their euploid progenies also lends support to recent suggestions that aneuploidy
      may have played an important and protracted role in polyploid genome evolution. 

PMID- 26295563
TI  - Time-dependent prognostic score matching for recurrent event analysis to evaluate
      a treatment assigned during follow-up.
AB  - Recurrent events often serve as the outcome in epidemiologic studies. In some
      observational studies, the goal is to estimate the effect of a new or
      "experimental" (i.e., less established) treatment of interest on the recurrent
      event rate. The incentive for accepting the new treatment may be that it is more
      available than the standard treatment. Given that the patient can choose between
      the experimental treatment and conventional therapy, it is of clinical importance
      to compare the treatment of interest versus the setting where the experimental
      treatment did not exist, in which case patients could only receive no treatment
      or the standard treatment. Many methods exist for the analysis of recurrent
      events and for the evaluation of treatment effects. However, methodology for the
      intersection of these two areas is sparse. Moreover, care must be taken in
      setting up the comparison groups in our setting; use of existing methods
      featuring time-dependent treatment indicators will generally lead to a biased
      treatment effect since the comparison group construction will not properly
      account for the timing of treatment initiation. We propose a sequential
      stratification method featuring time-dependent prognostic score matching to
      estimate the effect of a time-dependent treatment on the recurrent event rate.
      The performance of the method in moderate-sized samples is assessed through
      simulation. The proposed methods are applied to a prospective clinical study in
      order to evaluate the effect of living donor liver transplantation on
      hospitalization rates; in this setting, conventional therapy involves remaining
      on the wait list or receiving a deceased donor transplant. 

PMID- 26295564
TI  - Finnish guidelines for the treatment of laryngitis, wheezing bronchitis and
      bronchiolitis in children.
AB  - Evidence-based guidelines are needed to harmonise and improve the diagnostics and
      treatment of children's lower respiratory tract infections. Following a
      professional literature search, an interdisciplinary working group evaluated and
      graded the available evidence and constructed guidelines for treating laryngitis,
      bronchitis, wheezing bronchitis and bronchiolitis. CONCLUSION: Currently
      available drugs were not effective in relieving cough symptoms. Salbutamol
      inhalations could relieve the symptoms of wheezing bronchitis and should be
      administered via a holding chamber. Nebulised adrenaline or inhaled or oral
      glucocorticoids did not reduce hospitalisation rates or relieve symptoms in
      infants with bronchiolitis and should not be routinely used.

PMID- 26295565
TI  - Intralesional immunotherapy with tuberculin purified protein derivative (PPD) in
      recalcitrant wart: A randomized, placebo-controlled, double-blind clinical trial
      including an extra group of candidates for cryotherapy.
AB  - BACKGROUND: Due to paucity of randomized clinical trials, intralesional
      immunotherapy has not been yet accepted as a standard therapeutic method.
      OBJECTIVE: To examine the efficacy and safety of intralesional immunotherapy with
      tuberculin purified protein derivative (PPD) for treating recalcitrant wart.
      METHODS: In this randomized, placebo-controlled, double-blind clinical trial, a
      total of 69 patients with recalcitrant warts received either intralesional PPD
      antigen (n = 35) or intralesional saline (n = 34) for six times at 2-week
      intervals. A third group of candidates for cryotherapy (n = 33) was also
      included. The decrease in lesion size (good: complete response, intermediate: 50
      99% improvement, poor: <50% improvement), adverse effects and recurrence within 6
      month follow-up were documented. RESULTS: At the final session, good,
      intermediate and poor responses were observed in 77.1%, 22.9% and 0% of the PPD
      patients; 0%, 14.7% and 85.3% of the placebo patients and 18.2%, 33.3% and 48.5%
      of the cryotherapy patients, respectively (PPD versus placebo: p < 0.001; PPD
      versus cryotherapy: p < 0.001). No significant complication was seen in the PPD
      group. The recurrence rate was 8.6%, 5.9% and 24.2% in the PPD, placebo and
      cryotherapy groups, respectively (p > 0.05). CONCLUSION: Intralesional
      immunotherapy with PPD antigen is highly effective and safe for treating
      recalcitrant warts. CLINICAL TRIAL REGISTRATION: IRCT201407089844N3 in the
      Iranian Registry of Clinical Trials (IRCT).

PMID- 26295566
TI  - The Behavior Response of Amphipods Infected by Hedruris suttonae (Nematoda) and
      Pseudocorynosoma sp. (Acanthocephala).
AB  - The manipulation of intermediate host behavior may increase chances of parasite
      transmission to the definitive host. In freshwater environments of the
      Neotropical Region, studies on behavioral manipulations by parasites are rare,
      and the majority of these consider only a single parasite species and/or 1 life
      stage of a particular parasite species. In Andean Patagonian lakes of Argentina,
      the amphipod Hyalella patagonica is infected by larvae of the fish nematode
      Hedruris suttonae and by the bird acanthocephalan Pseudocorynosoma sp. The 3
      objectives of the present study were to determine whether H. suttonae and
      Pseudocorynosoma sp. differ in their effects on behavior of H. patagonica ,
      whether such modification is associated with parasite development, and to assess
      the associations between behavioral traits. From naturally parasitized amphipods,
      activity (swimming levels) and phototaxis (light preference) was measured. Only
      in phototaxis trials did larvae of H. suttonae induce significantly higher levels
      of photophilia, suggesting that they are manipulative. Scores of activity and
      phototaxis were positive and significantly related for non-parasitized female
      amphipods and for amphipods parasitized by larvae of Pseudocorynosoma sp. but
      were not associated in amphipods parasitized with larvae of H. suttonae
      (infective and non-infective), suggesting that infection separated the
      relationship between these variables. 

PMID- 26295567
TI  - Electrochemical monitoring of colloidal silver nanowires in aqueous samples.
AB  - Silver nanowires (NWs) are increasingly utilized in technological materials and
      consumer products, but an effective analytical technique is not yet available to
      measure their concentration in the environment. Here, we present an
      electrochemical method to quantify Ag NWs suspended in aqueous solution. Using
      linear sweep voltammetry, the Ag NWs are identified by the peak potential while
      their concentration is revealed by the intensity of the peak current. The peak
      current varies linearly with the Ag NW concentration with a low detection limit
      of 3.50 ng mL(-1). This method is also successfully applied to quantify Ag NWs in
      mixtures with nanoparticles, through their specific oxidation behavior, and in
      wastewater obtained after the Ag NW film preparation process. 

PMID- 26295568
TI  - Lamellipodin promotes actin assembly by clustering Ena/VASP proteins and
      tethering them to actin filaments.
AB  - Enabled/Vasodilator (Ena/VASP) proteins promote actin filament assembly at
      multiple locations, including: leading edge membranes, focal adhesions, and the
      surface of intracellular pathogens. One important Ena/VASP regulator is the mig
      10/Lamellipodin/RIAM family of adaptors that promote lamellipod formation in
      fibroblasts and drive neurite outgrowth and axon guidance in neurons. To better
      understand how MRL proteins promote actin network formation we studied the
      interactions between Lamellipodin (Lpd), actin, and VASP, both in vivo and in
      vitro. We find that Lpd binds directly to actin filaments and that this
      interaction regulates its subcellular localization and enhances its effect on
      VASP polymerase activity. We propose that Lpd delivers Ena/VASP proteins to
      growing barbed ends and increases their polymerase activity by tethering them to
      filaments. This interaction represents one more pathway by which growing actin
      filaments produce positive feedback to control localization and activity of
      proteins that regulate their assembly. 

PMID- 26295570
TI  - Correction: Treatment Frequency and Dosing Interval of Ranibizumab and
      Aflibercept for Neovascular Age-Related Macular Degeneration in Routine Clinical
      Practice in the USA.

PMID- 26295569
TI  - SPEAR Trial: Smartphone Pediatric ElectrocARdiogram Trial.
AB  - OBJECTIVES: Smartphone-enabled ECG devices have the potential to improve patient
      care by enabling remote ECG assessment of patients with potential and diagnosed
      arrhythmias. This prospective study aimed to assess the usefulness of pediatric
      ECG tracings generated by the AliveCor device (Oklahoma City, OK) and to assess
      user satisfaction. STUDY DESIGN: Enrolled pediatric patients with documented
      paroxysmal arrhythmia used the AliveCor device over a yearlong study period.
      Pediatric electrophysiologists reviewed all transmitted ECG tracings. Patient
      completed surveys were analyzed to assess user satisfaction. RESULTS: 35 patients
      were enrolled with the following diagnoses: supraventricular tachycardia (SVT,
      57%), atrial fibrillation (AF, 11%), ectopic atrial tachycardia (EAT, 6%), atrial
      tachycardia (AT, 3%), and ventricular tachycardia (VT, 23%). A total of 238
      tracings were received from 20 patients, 96% of which were of diagnostic quality
      for sinus rhythm, sinus tachycardia, SVT, and AF. 126 patient satisfaction
      surveys (64% from parents) were completed. 98% of the survey responses indicated
      that it was easy to obtain tracings, 93% found it easy to transmit the tracings,
      98% showed added comfort in managing arrhythmia by having the device, and 93%
      showed interest in continued use of the device after the study period ended.
      CONCLUSIONS: Smartphone-enabled ECG devices can generate tracings of diagnostic
      quality in children. User satisfaction was extremely positive. Use of the device
      to manage certain patients with AF and SVT showcases the future role of remote
      ECGs in the successful outpatient management of arrhythmias in children by
      potentially reducing Emergency Department visits and healthcare costs.

PMID- 26295571
TI  - Potential Therapeutic Effect of Natural Killer Cells on Doxorubicin-Resistant
      Breast Cancer Cells In Vitro.
AB  - OBJECTIVE: The aim of this study was to explore the therapeutic effect of natural
      killer (NK) cells on human doxorubicin-sensitive and resistant breast
      adenocarcinoma. METHODS: Human doxorubicin-sensitive and resistant breast cancer
      cell lines (MCF-7 and MCF-7/ADR) were tagged with renilla luciferase (Rluc) (MCF
      7/RC and MCF-7/ADR/RC). NK cells were tagged with enhanced firefly luciferase
      (effluc) using a recombinant retrovirus transfection (NKF). Expression of Rluc,
      effluc, and NK cell surface markers CD16, CD56 as well as death receptors, DR4
      and DR5, were assessed by using flow cytometry. In vitro cytotoxic effect of NK
      to MCF-7 and MCF-7/ADR was measured and in vivo bioluminescence imaging was also
      performed to visualize MCF-7/RC, MCF-7/ADR, and NKF in an animal model. RESULTS:
      NK92-MI, MCF-7, and MCF-7/ADR cells were successfully labeled with Rluc or
      effluc. Both the target breast cancer cells (with Rluc) and therapeutic NK cells
      (with effluc) were noninvasively visualized in nude mice. Doxorubicin-resistant
      breast cancer cells (MCF-7/ADR) presented a higher expression of DR5 and were
      more sensitive to NK cells compared with doxorubicin-sensitive breast cancer
      cells (MCF-7). CONCLUSION: The results of present study suggest that NK cell
      therapy has a therapeutic effect on doxorubicin-sensitive and resistant breast
      cancer cells.

PMID- 26295572
TI  - Stereoselective Regulation of P-gp Activity by Clausenamide Enantiomers in Caco
      2, KB/KBv and Brain Microvessel Endothelial Cells.
AB  - The (-)- and (+)-clausenamide (CLA) enantiomers have different pharmacokinetic
      effects in animals, but their association with putative stereoselective
      regulation of P-glycoprotein (P-gp) remains unclear. Using three cells expressing
      P-gp-Caco-2, KBv and rat brain microvessel endothelial cells(RBMEC), this study
      investigated the association of CLA enantiomers with P-gp. The results showed
      that the rhodamine 123 (Rh123) accumulation, an indicator of P-gp activity, in
      Caco-2, KBv and RBMECs was increased by (-)CLA (1 or 5 MUmol/L) at 8.2%-28.5%,
      but reduced by (+)CLA at 11.7%-25.9%, showing stereoselectivity in their
      regulation of P-gp activity. Following co-treatment of these cells with each CLA
      enantiomer and verapamil as a P-gp inhibitor, the (+)-isomer clearly antagonized
      the inhibitory effects of verapamil on P-gp efflux, whereas the (-)-isomer had
      slightly synergistic or additive effects. When higher concentrations (5 or 10
      MUmol/L) of CLA enantiomers were added, the stimulatory effects of the (+)-isomer
      were converted into inhibitory ones, leading to an enhanced intracellular uptake
      of Rh123 by 24.5%-58.2%; but (-)-isomer kept its inhibition to P-gp activity,
      causing 30.0%-63.0% increase in the Rh123 uptake. The biphasic effects of (+)CLA
      were confirmed by CLA uptake in the Caco-2 cells. (+)CLA at 1 MUmol/L had
      significantly lower intracellular uptake than (-)CLA with a ratio[(-)/(+)] of
      2.593, which was decreased to 2.167 and 1.893 after CLA concentrations increased
      to 2.5 and 5 MUmol/L. Besides, in the non-induced KB cells, (+)CLA(5 MUmol/L)
      upregulated P-gp expression at 54.5% relative to vehicle control, and decreased
      Rh123 accumulation by 28.2%, while (-)CLA(5 MUmol/L) downregulated P-gp
      expression at 15.9% and increased Rh123 accumulation by 18.0%. These results
      suggested that (-)CLA could be a P-gp inhibitor and (+)CLA could be a modulator
      with concentration-dependent biphasic effects on P-gp activity, which may result
      in drug-drug interactions when combined with other P-gp substrate drugs. 

PMID- 26295573
TI  - Wheat Bran Enhances the Cytotoxicity of Immobilized Alcaligenes aquatilis F8
      against Microcystis aeruginosa.
AB  - Algicidal bacteria offer a promising option for killing cyanobacteria. Therefore,
      a new Alcaligenes aquatilis strain F8 was isolated to control Microcystis
      aeruginosa in this study. The algicidal activity of strain F8 was dependent on
      the cell density of M. aeruginosa, and the maximal algicidal rate of the free
      bacterium reached 88.45% within 72 h. With a view to its application to the
      control of M. aeruginosa in the natural environment, strain F8 was immobilized in
      sodium alginate beads, but immobilization of the strain decreased its algicidal
      rate compared to that of the free bacterium. However, addition of wheat bran to
      the sodium alginate matrix used to immobilize strain F8 not only eliminated the
      adverse effects of immobilization on the bacteria but also resulted in an 8.83%
      higher algicidal rate of the immobilized than free bacteria. Exclusion and
      recovery methods were used to identify key ingredients of wheat bran and gain
      insight into the mechanism underlying the observed enhancement of algicidal
      activity. This analysis indicated that certain factors in wheat bran, including
      vitamins B1, B2, B9, and E were responsible for promoting bacterial growth and
      thereby improving the algicidal rate of immobilized strain F8. Our findings
      indicate that wheat bran is able to improve the algicidal efficiency of A.
      aquatilis strain F8 for killing M. aeruginosa and is a good source of not only
      carbon and nitrogen but also vitamins for bacteria. 

PMID- 26295574
TI  - Effect of Yeast Cell Morphology, Cell Wall Physical Structure and Chemical
      Composition on Patulin Adsorption.
AB  - The capability of yeast to adsorb patulin in fruit juice can aid in substantially
      reducing the patulin toxic effect on human health. This study aimed to
      investigate the capability of yeast cell morphology and cell wall internal
      structure and composition to adsorb patulin. To compare different yeast cell
      morphologies, cell wall internal structure and composition, scanning electron
      microscope, transmission electron microscope and ion chromatography were used.
      The results indicated that patulin adsorption capability of yeast was influenced
      by cell surface areas, volume, and cell wall thickness, as well as 1,3-beta
      glucan content. Among these factors, cell wall thickness and 1,3-beta-glucan
      content serve significant functions. The investigation revealed that patulin
      adsorption capability was mainly affected by the three-dimensional network
      structure of the cell wall composed of 1,3-beta-glucan. Finally, patulin
      adsorption in commercial kiwi fruit juice was investigated, and the results
      indicated that yeast cells could adsorb patulin from commercial kiwi fruit juice
      efficiently. This study can potentially simulate in vitro cell walls to enhance
      patulin adsorption capability and successfully apply to fruit juice industry. 

PMID- 26295575
TI  - Editorial: Inflammation and Atherosclerosis: The Role of Novel Biomarkers (Part
      I).

PMID- 26295578
TI  - Biased signaling: potential agonist and antagonist of PAR2.
AB  - Protease activated receptor 2 (PAR2) has emerged as one of the promising
      therapeutic targets to inhibit rapidly metastasizing breast cancer cells.
      However, its elusive molecular mechanism of activation and signaling has made it
      a difficult target for drug development. In this study, in silico methods were
      used to unfold PAR2 molecular mechanism of signaling based on the concept of GPCR
      receptor plasticity. Although, there are no conclusive evidences of the presence
      of specific endogenous ligands for PAR2, the efficacy of synthetic agonist and
      antagonist in PAR2 signaling has opened up the possibilities of ligand-mediated
      signaling. Furthermore, it has been proved that ligands specific for one GPCR can
      induce signaling in GPCRs belonging to other subfamilies. Therefore, the aim of
      this study was to identify potential agonists and antagonists from the GPCR
      ligand library (GLL), which may induce biased signaling in PAR2 using the concept
      of existence of multiple ligand-stabilized receptor conformations. The results of
      our in silico study suggest that PAR2 may show biased signaling mainly with
      agonists of serotonin type 1, beta-adrenergic type 1,3 and antagonists of
      substance K (NK1), serotonin type 2, dopamine type 4, and thromboxane receptors.
      Further, this study also throws light on the putative ligand-specific
      conformations of PAR2. Thus, the results of this study provide structural
      insights to putative conformations of PAR2 and also gives initial clues to
      medicinal chemists for rational drug design targeting this challenging receptor. 

PMID- 26295577
TI  - Impact of Adverse Childhood Experiences on Intimate Partner Violence Perpetration
      among Sri Lankan Men.
AB  - In Sri Lanka, over one in three women experience intimate partner violence (IPV)
      victimization in their lifetime, making it a serious public health concern.
      Adverse childhood experiences (ACEs) such as child abuse and neglect, witnessing
      domestic violence, parental separation, and bullying are also widespread. Studies
      in Western settings have shown positive associations between ACEs and IPV
      perpetration in adulthood, but few have examined this relationship in a non
      Western context. In the present study, we examined the association of ACEs with
      IPV perpetration among Sri Lankan men surveyed for the UN Multi-Country Study on
      Men and Violence in Asia and the Pacific. We found statistically significant
      positive associations between the number of ACE categories (ACE score) and
      emotional, financial, physical, and sexual IPV perpetration among Sri Lankan men.
      We analyzed the contributions of each ACE category and found that childhood abuse
      was strongly associated with perpetration of IPV in adulthood, with sexual abuse
      associated with the greatest increase in odds of perpetration (Adjusted odds
      ratio 2.36; 95% confidence interval: 1.69, 3.30). Witnessing abuse of one's
      mother was associated with the greatest increase in the odds of perpetrating
      physical IPV (AOR 1.82; 95% CI: 1.29, 2.58), while lack of a male parental figure
      was not associated with physical IPV perpetration (AOR 0.76; 95% CI: 0.53, 1.09).
      These findings support a social learning theory of IPV perpetration, in which
      children who are exposed to violence learn to perpetrate IPV in adulthood. They
      also suggest that in Sri Lanka, being raised in a female-headed household does
      not increase the risk of IPV perpetration in adulthood compared to being raised
      in a household with a male parental figure. The relationship between being raised
      in a female-headed household (the number of which increased dramatically during
      Sri Lanka's recent civil war) and perpetration of IPV warrants further study.
      Interventions that aim to decrease childhood abuse in Sri Lanka could both
      protect children now and reduce IPV in the future, decreasing violence on
      multiple fronts. 

PMID- 26295580
TI  - Retraction: Glyphosate Use Predicts ADHD Hospital Discharges in the Healthcare
      Cost and Utilization Project Net (HCUPnet): A Two-Way Fixed-Effects Analysis.

PMID- 26295576
TI  - The Aspergillus fumigatus pkcA G579R Mutant Is Defective in the Activation of the
      Cell Wall Integrity Pathway but Is Dispensable for Virulence in a Neutropenic
      Mouse Infection Model.
AB  - Aspergillus fumigatus is an opportunistic human pathogen, which causes the life
      threatening disease, invasive pulmonary aspergillosis. In fungi, cell wall
      homeostasis is controlled by the conserved Cell Wall Integrity (CWI) pathway. In
      A. fumigatus this signaling cascade is partially characterized, but the
      mechanisms by which it is activated are not fully elucidated. In this study we
      investigated the role of protein kinase C (PkcA) in this signaling cascade. Our
      results suggest that pkcA is an essential gene and is activated in response to
      cell wall stress. Subsequently, we constructed and analyzed a non-essential A.
      fumigatus pkcAG579R mutant, carrying a Gly579Arg substitution in the PkcA C1B
      regulatory domain. The pkcAG579R mutation has a reduced activation of the
      downstream Mitogen-Activated Protein Kinase, MpkA, resulting in the altered
      expression of genes encoding cell wall-related proteins, markers of endoplasmic
      reticulum stress and the unfolded protein response. Furthermore, PkcAG579R is
      involved in the formation of proper conidial architecture and protection to
      oxidative damage. The pkcAG579R mutant elicits increased production of TNF-alpha
      and phagocytosis but it has no impact on virulence in a murine model of invasive
      pulmonary aspergillosis. These results highlight the importance of PkcA to the
      CWI pathway but also indicated that additional regulatory circuits may be
      involved in the biosynthesis and/or reinforcement of the A. fumigatus cell wall
      during infection. 

PMID- 26295579
TI  - Effects of Air Pollution and the Introduction of the London Low Emission Zone on
      the Prevalence of Respiratory and Allergic Symptoms in Schoolchildren in East
      London: A Sequential Cross-Sectional Study.
AB  - The adverse effects of traffic-related air pollution on children's respiratory
      health have been widely reported, but few studies have evaluated the impact of
      traffic-control policies designed to reduce urban air pollution. We assessed
      associations between traffic-related air pollutants and respiratory/allergic
      symptoms amongst 8-9 year-old schoolchildren living within the London Low
      Emission Zone (LEZ). Information on respiratory/allergic symptoms was obtained
      using a parent-completed questionnaire and linked to modelled annual air
      pollutant concentrations based on the residential address of each child, using a
      multivariable mixed effects logistic regression analysis. Exposure to traffic
      related air pollutants was associated with current rhinitis: NOx (OR 1.01, 95% CI
      1.00-1.02), NO2 (1.03, 1.00-1.06), PM10 (1.16, 1.04-1.28) and PM2.5 (1.38, 1.08
      1.78), all per MUg/m3 of pollutant, but not with other respiratory/allergic
      symptoms. The LEZ did not reduce ambient air pollution levels, or affect the
      prevalence of respiratory/allergic symptoms over the period studied. These data
      confirm the previous association between traffic-related air pollutant exposures
      and symptoms of current rhinitis. Importantly, the London LEZ has not
      significantly improved air quality within the city, or the respiratory health of
      the resident population in its first three years of operation. This highlights
      the need for more robust measures to reduce traffic emissions. 

PMID- 26295581
TI  - Comparative Analysis of Two Gene-Targeting Approaches Challenges the Tumor
      Suppressive Role of the Protein Kinase MK5/PRAK.
AB  - MK5 (MAPK-activated protein kinase 5) or PRAK (p38-regulated and -activated
      kinase) are alternative names for a serine/threonine protein kinase downstream to
      ERK3/4 and p38 MAPK. A previous gene targeting approach for MK5/PRAK (termed here
      MK5/PRAK-Deltaex8) revealed a seemingly tumor-suppressive role of MK5/PRAK in
      DMBA-induced one step skin carcinogenesis and Ras-induced transformation. Here we
      demonstrate that an alternative targeting strategy of MK5/PRAK (termed MK5/PRAK
      Deltaex6) increased neither tumor incidence in the one step skin carcinogenesis
      model, nor Ras-induced transformation in primary cells. Interestingly, due to the
      targeting strategies and exon skipping both knockouts do not completely abolish
      the generation of MK5/PRAK protein, but express MK5/PRAK deletion mutants with
      different biochemical properties depending on the exon targeted: Targeting of
      exon 6 leads to expression of an unstable cytoplasmic catalytically inactive
      MK5/PRAK-Deltaex6 mutant while targeting of exon 8 results in a more stable
      nuclear MK5/PRAK-Deltaex8 mutant with residual catalytic activity. The different
      properties of the MK5/PRAK deletion mutants could be responsible for the observed
      discrepancy between the knockout strains and challenge the role of MK5/PRAK in
      p53-dependent tumor suppression. Further MK5/PRAK knockout and knock-in mouse
      strains will be necessary to assign a physiological function to MK5/PRAK in this
      model organism. 

PMID- 26295582
TI  - Extremely High Phosphate Sorption Capacity in Cu-Pb-Zn Mine Tailings.
AB  - Elevated inorganic phosphate (Pi) concentrations in pore water of amended
      tailings under direct revegetation may cause toxicity in some native woody
      species but not native forbs or herb species, all of which are key constituents
      in target native plant communities for phytostabilizing base metal mine tailings.
      As a result, Pi sorption capacity has been quantified by a conventional batch
      procedure in three types of base metal mine tailings sampled from two copper (Cu)
      lead (Pb)-zinc (Zn) mines, as the basis for Pi-fertiliser addition. It was found
      that the Pi-sorption capacity in the tailings and local soil was extremely high,
      far higher than highly weathered agricultural soils in literature, but similar to
      those of volcanic ash soils. The Langmuir P-sorption maximum was up to 7.72,
      4.12, 4.02 and 3.62 mg P g-1 tailings, in the fresh tailings of mixed Cu-Pb-Zn
      streams (MIMTD7), the weathered tailings of mixed Cu-Pb-Zn streams (MIMTD5), EHM
      TD (fresh Cu-stream, high magnetite content) and local soil (weathered shale and
      schist), respectively. Physicochemical factors highly correlated with the high Pi
      sorption in the tailings were fine particle distribution, oxalate and dithionite
      citrate-bicarbonate extractable Fe (FeO and Fed), oxalate-extractable Al and Mn,
      and the levels of soluble Cd and Zn, and total S and Fe. Large amounts of
      amorphous Fe oxides and oxyhydroxides may have been formed from the oxidation of
      pyritic materials and redox cycles of Fe-minerals (such as pyrite (FeS2),
      ankerite (Ca(Fe Mg)(CO3)2 and siderite (FeCO3), as indicated by the extractable
      FeO values. The likely formation of sparingly soluble Zn-phosphate in the Pb-Zn
      tailings containing high levels of Zn (from sphalerite ((Zn,Fe)S, ZnS, (Zn,Cd)S))
      may substantially lower soluble Zn levels in the tailings through high rates of
      Pi-fertiliser addition. As a result, the possibility of P-toxicity in native
      plant species caused by the addition of soluble phosphate fertilizers would be
      minimal. 

PMID- 26295583
TI  - Genome Wide Expression Profiling of Cancer Cell Lines Cultured in Microgravity
      Reveals Significant Dysregulation of Cell Cycle and MicroRNA Gene Networks.
AB  - Zero gravity causes several changes in metabolic and functional aspects of the
      human body and experiments in space flight have demonstrated alterations in
      cancer growth and progression. This study reports the genome wide expression
      profiling of a colorectal cancer cell line-DLD-1, and a lymphoblast leukemic cell
      line-MOLT-4, under simulated microgravity in an effort to understand central
      processes and cellular functions that are dysregulated among both cell lines.
      Altered cell morphology, reduced cell viability and an aberrant cell cycle
      profile in comparison to their static controls were observed in both cell lines
      under microgravity. The process of cell cycle in DLD-1 cells was markedly
      affected with reduced viability, reduced colony forming ability, an apoptotic
      population and dysregulation of cell cycle genes, oncogenes, and cancer
      progression and prognostic markers. DNA microarray analysis revealed 1801
      (upregulated) and 2542 (downregulated) genes (>2 fold) in DLD-1 cultures under
      microgravity while MOLT-4 cultures differentially expressed 349 (upregulated) and
      444 (downregulated) genes (>2 fold) under microgravity. The loss in cell
      proliferative capacity was corroborated with the downregulation of the cell cycle
      process as demonstrated by functional clustering of DNA microarray data using
      gene ontology terms. The genome wide expression profile also showed significant
      dysregulation of post transcriptional gene silencing machinery and multiple
      microRNA host genes that are potential tumor suppressors and proto-oncogenes
      including MIR22HG, MIR17HG and MIR21HG. The MIR22HG, a tumor-suppressor gene was
      one of the highest upregulated genes in the microarray data showing a 4.4 log
      fold upregulation under microgravity. Real time PCR validated the dysregulation
      in the host gene by demonstrating a 4.18 log fold upregulation of the miR-22
      microRNA. Microarray data also showed dysregulation of direct targets of miR-22,
      SP1, CDK6 and CCNA2. 

PMID- 26295584
TI  - What it Takes to Get Passed On: Message Content, Style, and Structure as
      Predictors of Retransmission in the Boston Marathon Bombing Response.
AB  - Message retransmission is a central aspect of information diffusion. In a
      disaster context, the passing on of official warning messages by members of the
      public also serves as a behavioral indicator of message salience, suggesting that
      particular messages are (or are not) perceived by the public to be both
      noteworthy and valuable enough to share with others. This study provides the
      first examination of terse message retransmission of official warning messages in
      response to a domestic terrorist attack, the Boston Marathon Bombing in 2013.
      Using messages posted from public officials' Twitter accounts that were active
      during the period of the Boston Marathon bombing and manhunt, we examine the
      features of messages that are associated with their retransmission. We focus on
      message content, style, and structure, as well as the networked relationships of
      message senders to answer the question: what characteristics of a terse message
      sent under conditions of imminent threat predict its retransmission among members
      of the public? We employ a negative binomial model to examine how message
      characteristics affect message retransmission. We find that, rather than any
      single effect dominating the process, retransmission of official Tweets during
      the Boston bombing response was jointly influenced by various message content,
      style, and sender characteristics. These findings suggest the need for more work
      that investigates impact of multiple factors on the allocation of attention and
      on message retransmission during hazard events. 

PMID- 26295585
TI  - Creatinine Change on Vasoconstrictors as Mortality Surrogate in Hepatorenal
      Syndrome: Systematic Review & Meta-Analysis.
AB  - BACKGROUND AND AIMS: Hepatorenal syndrome is a severe complication of cirrhosis
      and associates with significant mortality. Vasoconstrictor medications improve
      renal function in patients with hepatorenal syndrome. However, it is unclear to
      what extent changes in serum creatinine during treatment may act as a surrogate
      for changes in mortality. We have performed a meta-analysis of randomized trials
      of vasoconstrictors assessing the association between changes in serum
      creatinine, taken as a continuous variable, and mortality, both while on
      treatment and during the follow-up period for survivors. METHODS: The electronic
      databases of PubMed, Web of Science and Embase were searched for randomized
      trials evaluating the efficacy of vasoconstrictor therapy for treatment of HRS
      type 1 or 2. The relative risk (RR) for mortality was calculated against delta
      creatinine. The proportion of treatment effect explained (PTE) was calculated for
      delta creatinine. RESULTS: Seven trials enrolling 345 patients were included. The
      correlation between delta creatinine and ln (RR) was moderately good (R2 = 0.61).
      The intercept and parameter estimate indicated a fall in creatinine while on
      treatment of 1 mg/dL resulted in a 27% reduction in RR for mortality compared to
      the control arm. In patients surviving the treatment period, a fall in creatinine
      while on treatment of 1 mg/dL resulted in a 16% reduction in RR for post
      treatment mortality during follow-up. The PTE of delta creatinine for overall
      mortality was 0.91 and 0.26 for post-treatment mortality. CONCLUSIONS: Changes in
      serum creatinine in response to vasoconstrictor therapy appear to be a valid
      surrogate for mortality, even in the period following the completion of
      treatment.

PMID- 26295586
TI  - Core Outcomes and Common Data Elements in Chronic Subdural Hematoma: A Systematic
      Review of the Literature Focusing on Reported Outcomes.
AB  - The plethora of studies in chronic subdural hematoma (CSDH) has not resulted in
      the development of an evidence-based treatment strategy, largely due to
      heterogeneous outcome measures that preclude cross-study comparisons and
      guideline development. This study aimed to identify and quantify the
      heterogeneity of outcome measures reported in the CSDH literature and to build a
      case for the development of a consensus-based core outcome set. This systematic
      review adhered to the Preferred Reporting Items for Systematic Reviews and Meta
      Analyses (PRISMA) statement and was registered with the PROSPERO international
      prospective register of systematic reviews (CRD42014007266). All full-text
      English language studies with >10 patients (prospective) or >100 patients
      (retrospective) published after 1990 examining clinical outcomes in CSDH were
      eligible for inclusion. One hundred two eligible studies were found. There were
      14 (13.7%) randomized controlled trials, one single arm trial (1.0%), 25 (24.5%)
      cohort comparison studies, and 62 (60.8%) prospective or retrospective cohort
      studies. Outcome domains reported by the studies included mortality (63.8% of
      included studies), recurrence (94.1%), complications (48.0%), functional outcomes
      (40.2%), and radiological (38.2%) outcomes. There was significant heterogeneity
      in the definitions of the outcome measures, as evidenced by the seven different
      definitions of the term "recurrence," with no definition given in 19 studies. The
      time-points of assessment for all the outcome domains varied greatly from
      inpatient/hospital discharge to 18 months. This study establishes and quantifies
      the heterogeneity of outcome measure reporting in CSDH and builds the case for
      the development of a robust consensus-based core outcome set for future studies
      to adhere to as part of the Core Outcomes and Common Data Elements in CSDH (CODE
      CSDH) project.

PMID- 26295588
TI  - Emerging data on the incidence of concussion in football practice at all levels
      of amateur play.
AB  - There has been increasing concern, particularly in the US, about potential long
      term neurological deterioration syndromes seen in the US football players.
      Recurrent concussions are a potential area of concern. The authors of this paper
      have used data bases from three levels of amateur US football to identify the
      rate and risk of concussion injury in both football games and practice at the
      youth, high school, and college levels. This information is very important
      initial data around concussion rates at these levels. 

PMID- 26295587
TI  - Formation and Dynamics of Waves in a Cortical Model of Cholinergic Modulation.
AB  - Acetylcholine (ACh) is a regulator of neural excitability and one of the
      neurochemical substrates of sleep. Amongst the cellular effects induced by
      cholinergic modulation are a reduction in spike-frequency adaptation (SFA) and a
      shift in the phase response curve (PRC). We demonstrate in a biophysical model
      how changes in neural excitability and network structure interact to create three
      distinct functional regimes: localized asynchronous, traveling asynchronous, and
      traveling synchronous. Our results qualitatively match those observed
      experimentally. Cortical activity during slow wave sleep (SWS) differs from that
      during REM sleep or waking states. During SWS there are traveling patterns of
      activity in the cortex; in other states stationary patterns occur. Our model is a
      network composed of Hodgkin-Huxley type neurons with a M-current regulated by
      ACh. Regulation of ACh level can account for dynamical changes between functional
      regimes. Reduction of the magnitude of this current recreates the reduction in
      SFA the shift from a type 2 to a type 1 PRC observed in the presence of ACh. When
      SFA is minimal (in waking or REM sleep state, high ACh) patterns of activity are
      localized and easily pinned by network inhomogeneities. When SFA is present
      (decreasing ACh), traveling waves of activity naturally arise. A further decrease
      in ACh leads to a high degree of synchrony within traveling waves. We also show
      that the level of ACh determines how sensitive network activity is to synaptic
      heterogeneity. These regimes may have a profound functional significance as
      stationary patterns may play a role in the proper encoding of external input as
      memory and traveling waves could lead to synaptic regularization, giving unique
      insights into the role and significance of ACh in determining patterns of
      cortical activity and functional differences arising from the patterns. 

PMID- 26295589
TI  - Overcoming difficulty in diagnosis and differential diagnosis of Crohn's disease:
      the potential role of serological and genetic tests.
AB  - Crohn's disease (CD) represents a heterogeneous group of chronic inflammatory
      disorders with various phenotypes. Establishing a definite diagnosis of CD should
      be based upon a combined assessment of clinical, endoscopic, radiological and
      pathological features. Although segmental disease distribution, transmural
      inflammation and non-caseating epithelioid granulomas have been considered as a
      'hallmarks' for CD, clear diagnosis of CD in some patients has been challenging,
      due to overlapping endoscopic, radiographic and histologic features with other
      inflammatory bowel disease-like conditions. Laboratory markers (serological and
      genetic tests) may provide additional clues for the diagnosis and differential
      diagnosis of CD. This review focuses on the application of the currently
      available serological and genomic markers and in diagnosis and differential
      diagnosis of CD. 

PMID- 26295590
TI  - Broadband ultrafast photoprotection by oxybenzone across the UVB and UVC spectral
      regions.
AB  - Recent studies have shed light on the energy dissipation mechanism of oxybenzone,
      a common ingredient in commercial sunscreens. After UVA photoexcitation, the
      dissipation mechanism may be understood in terms of an initial ultrafast excited
      state enol -> keto tautomerisation, followed by nonadiabatic transfer to the
      ground electronic state and subsequent collisional relaxation to the starting
      enol tautomer. We expand on these studies using femtosecond transient electronic
      absorption spectroscopy to understand the non-radiative relaxation pathways of
      oxybenzone in cyclohexane and in methanol after UVB and UVC excitation. We find
      that the relaxation pathway may be understood in the same way as when exciting in
      the UVA region, concluding that oxybenzone displays proficient broadband non
      radiative photoprotection, and thus photophysically justifying its inclusion in
      sunscreen mixtures. 

PMID- 26295592
TI  - Measuring Satisfaction and Usability of FaceTime for Virtual Visits in Patients
      with Uncontrolled Diabetes.
AB  - BACKGROUND: The interconnection capabilities of mobile device platforms offer the
      opportunity for efficient delivery of healthcare and afford the potential to
      increase access to patients with chronic diseases. With the increased incidence
      of diabetes mellitus in the United States, innovative strategies to improve
      access to healthcare teams are necessary. The aim of this study was to determine
      satisfaction and usability of patients and diabetes care team members with
      videoconferencing capabilities using an iPad(r)2 (Apple, Cupertino, CA).
      MATERIALS AND METHODS: Patients were provided an iPad2 with videoconferencing
      capabilities using FaceTime(r) (Apple) (n=34). Patients were scheduled virtual
      visits with a multidisciplinary diabetes care team. Participants were given a 12
      item survey at Day 90 of study enrollment. Members of the diabetes care team were
      provided a five-item survey at Days 30, 90, and 180 of the study period. RESULTS:
      Sixty-five percent of patients reported satisfaction using FaceTime for visits.
      Seventy-six percent of patients agreed that FaceTime was effective in improving
      diabetes. Overall satisfaction with technology declined over the study period
      among members of the diabetes care team. CONCLUSIONS: The results provide
      practical information on using video technology to conduct chronic disease care.
      Overall, patients and the diabetes care team reported positive ratings in terms
      of usability and satisfaction with selected technology for virtual visits.
      Although limitations using FaceTime virtual visits exist, FaceTime has potential
      to increase patient access to a multidisciplinary care team. Additional research
      is warranted to determine economic and clinical outcomes for two-way visual
      technology.

PMID- 26295593
TI  - Improving Functional Outcomes for Vascular Amputees Through Use of Mirror Therapy
      and Elimination of the Effects of Electromagnetic Fields.
AB  - The objective of this pilot study was to investigate the effectiveness of
      combining an amputee limb cover to eliminate the effects of electromagnetic
      fields (i.e., pain) and a Mirror Therapy exercise program to improve functional
      outcomes for vascular amputees. A cross-sectional repeated-measures design was
      used with 14 participants with either acute amputations or surgery at least 8 to
      24 months previously. The 4-week intervention included the use of an amputee limb
      cover and mirror therapy exercises each day. The outcome measures were activities
      of daily living interference (e.g., self-care, walking, car transfer, low chair
      transfer, sleep), and well-being (e.g., satisfaction, mood, quality of life) at
      three times (pre- and posttreatment and maintenance). Participants with acute
      amputations made significant improvements in the areas of self-care, walking, car
      transfer, sleep, mood, and quality of life, while the subacute participants
      improved significantly in sleep and satisfaction. A reduction in the time
      required before prosthetic fitting decreased from 12 weeks to 8 weeks for acute
      amputees and an improvement in wearing tolerance from 0-2 to 8-12 hours for the
      subacute amputees were unexpected results suggesting the combined intervention
      may improves the extent to which amputees can increase participation in their
      activities of everyday living. 

PMID- 26295594
TI  - A Cation-Directed Enantioselective Sulfur-Mediated Michael/Mannich Three
      Component Domino Reaction involving Chalcones as Michael Acceptors.
AB  - A new approach has been developed for an asymmetric sulfur-mediated three
      component intermolecular Michael/Mannich domino reaction using chalcones as
      Michael acceptors. This reaction is catalyzed by chiral quaternary ammonium salts
      derived from modified quinine and provides facile access to complex sulfur
      containing compounds with three contiguous stereogenic centers in yields of up to
      93%, with 95:5 dr and 95% ee. These compounds were further elaborated to give the
      equivalent of a chiral aza-Morita-Baylis-Hillman reaction involving chalcones and
      azetidines bearing four chiral centers. 

PMID- 26295591
TI  - MR Imaging of Knee Arthroplasty Implants.
AB  - Primary total knee arthroplasty is a highly effective treatment that relieves
      pain and improves joint function in a large percentage of patients. Despite an
      initially satisfactory surgical outcome, pain, dysfunction, and implant failure
      can occur over time. Identifying the etiology of complications is vital for
      appropriate management and proper timing of revision. Due to the increasing
      number of knee arthroplasties performed and decreasing patient age at
      implantation, there is a demand for accurate diagnosis to determine appropriate
      treatment of symptomatic joints following knee arthroplasty, and for monitoring
      of patients at risk. Magnetic resonance (MR) imaging allows for comprehensive
      imaging evaluation of the tissues surrounding knee arthroplasty implants with
      metallic components, including the polyethylene components. Optimized
      conventional and advanced pulse sequences can result in substantial metallic
      artifact reduction and afford improved visualization of bone, implant-tissue
      interfaces, and periprosthetic soft tissue for the diagnosis of arthroplasty
      related complications. In this review article, we discuss strategies for MR
      imaging around knee arthroplasty implants and illustrate the imaging appearances
      of common modes of failure, including aseptic loosening, polyethylene wear
      induced synovitis and osteolysis, periprosthetic joint infections, fracture,
      patellar clunk syndrome, recurrent hemarthrosis, arthrofibrosis, component
      malalignment, extensor mechanism injury, and instability. A systematic approach
      is provided for evaluation of MR imaging of knee implants. MR imaging with
      optimized conventional pulse sequences and advanced metal artifact reduction
      techniques can contribute important information for diagnosis, prognosis, risk
      stratification, and surgical planning.

PMID- 26295595
TI  - Citrifelins A and B, Citrinin Adducts with a Tetracyclic Framework from
      Cocultures of Marine-Derived Isolates of Penicillium citrinum and Beauveria
      felina.
AB  - Citrifelins A (1) and B (2), two citrinin adducts possessing a unique tetracyclic
      framework, were characterized from a coculture of marine-derived fungal isolates
      of Penicillium citrinum and Beauveria felina. Neither fungus produced these
      compounds when cultured alone under the same conditions. The structures of these
      adducts were elucidated on the basis of spectroscopic analysis, and the absolute
      configurations were assigned on the basis of TDDFT-ECD calculations. A hypothesis
      that adducts 1 and 2 might be derived from a citrinin derivative through a non
      pericyclic Michael reaction is proposed. Compounds 1, 2, and 5 showed inhibitory
      activities against several human and aquatic pathogens. 

PMID- 26295596
TI  - Queer Phenomenology, Sexual Orientation, and Health Care Spaces: Learning From
      the Narratives of Queer Women and Nurses in Primary Health Care.
AB  - Queer phenomenology as an interpretive framework can advance health research by
      illuminating why primary health care providers (HCPs) must move beyond
      definitions of sexuality as a set of reified identity formations indexed to
      normative gender, gender of partner, and sexual and reproductive practices. Our
      interviews with queer women participants and primary care nurses offer an
      implicit critique of heteronormative health care space, temporality, and power
      relations, as they form the lived experiences of our participants. We conclude by
      pointing to the limits of our methodology in exposing the larger relations of
      power that dictate experiences of heteronormative health care. 

PMID- 26295597
TI  - Investing in our nursing workforce.

PMID- 26295598
TI  - Interim nursing leadership: A win-win opportunity.

PMID- 26295599
TI  - How undergraduate students can contribute to EBP.

PMID- 26295601
TI  - Interprofessional shared governance: The VNSNY experience.

PMID- 26295602
TI  - Transformational leadership practices of CNOs.

PMID- 26295603
TI  - Bridging the gap between IT and nurse leaders.

PMID- 26295604
TI  - Lessons from a children's hospital.

PMID- 26295605
TI  - Leadership Q&A. The lowdown on managing down.

PMID- 26295606
TI  - Subjective Ratings of Fatigue and Vigor in Adults With Hearing Loss Are Driven by
      Perceived Hearing Difficulties Not Degree of Hearing Loss.
AB  - OBJECTIVES: Anecdotal reports and qualitative research suggests that fatigue is a
      common, but often overlooked, accompaniment of hearing loss which negatively
      affects quality of life. However, systematic research examining the relationship
      between hearing loss and fatigue is limited. In this study, the authors examined
      relationships between hearing loss and various domains of fatigue and vigor using
      standardized and validated measures. Relationships between subjective ratings of
      multidimensional fatigue and vigor and the social and emotional consequences of
      hearing loss were also explored. DESIGN: Subjective ratings of fatigue and vigor
      were assessed using the profile of mood states and the multidimensional fatigue
      symptom inventory-short form. To assess the social and emotional impact of
      hearing loss participants also completed, depending on their age, the hearing
      handicap inventory for the elderly or adults. Responses were obtained from 149
      adults (mean age = 66.1 years, range 22 to 94 years), who had scheduled a hearing
      test and/or a hearing aid selection at the Vanderbilt Bill Wilkerson Center
      Audiology clinic. These data were used to explore relationships between
      audiometric and demographic (i.e., age and gender) factors, fatigue, and hearing
      handicap scores. RESULTS: Compared with normative data, adults seeking help for
      their hearing difficulties in this study reported significantly less vigor and
      more fatigue. Reports of severe vigor/fatigue problems (ratings exceeding
      normative means by +/-1.5 standard deviations) were also increased in the study
      sample compared with that of normative data. Regression analyses, with
      adjustments for age and gender, revealed that the subjective percepts of fatigue,
      regardless of domain, and vigor were not strongly associated with degree of
      hearing loss. However, similar analyses controlling for age, gender, and degree
      of hearing loss showed a strong association between measures of fatigue and vigor
      (multidimensional fatigue symptom inventory-short form scores) and the social and
      emotional consequences of hearing loss (hearing handicap inventory for the
      elderly/adults scores). CONCLUSIONS: Adults seeking help for hearing difficulties
      are more likely to experience severe fatigue and vigor problems; surprisingly,
      this increased risk appears unrelated to degree of hearing loss. However, the
      negative psychosocial consequences of hearing loss are strongly associated with
      subjective ratings of fatigue, across all domains, and vigor. Additional research
      is needed to define the pathogenesis of hearing loss-related fatigue and to
      identify factors that may modulate and mediate (e.g., hearing aid or cochlear
      implant use) its impact.

PMID- 26295607
TI  - Cortical Auditory Evoked Potentials Recorded From Nucleus Hybrid Cochlear Implant
      Users.
AB  - OBJECTIVES: Nucleus Hybrid Cochlear Implant (CI) users hear low-frequency sounds
      via acoustic stimulation and high-frequency sounds via electrical stimulation.
      This within-subject study compares three different methods of coordinating
      programming of the acoustic and electrical components of the Hybrid device.
      Speech perception and cortical auditory evoked potentials (CAEP) were used to
      assess differences in outcome. The goals of this study were to determine whether
      (1) the evoked potential measures could predict which programming strategy
      resulted in better outcome on the speech perception task or was preferred by the
      listener, and (2) CAEPs could be used to predict which subjects benefitted most
      from having access to the electrical signal provided by the Hybrid implant.
      DESIGN: CAEPs were recorded from 10 Nucleus Hybrid CI users. Study participants
      were tested using three different experimental processor programs (MAPs) that
      differed in terms of how much overlap there was between the range of frequencies
      processed by the acoustic component of the Hybrid device and range of frequencies
      processed by the electrical component. The study design included allowing
      participants to acclimatize for a period of up to 4 weeks with each experimental
      program prior to speech perception and evoked potential testing. Performance
      using the experimental MAPs was assessed using both a closed-set consonant
      recognition task and an adaptive test that measured the signal-to-noise ratio
      that resulted in 50% correct identification of a set of 12 spondees presented in
      background noise. Long-duration, synthetic vowels were used to record both the
      cortical P1-N1-P2 "onset" response and the auditory "change" response (also known
      as the auditory change complex [ACC]). Correlations between the evoked potential
      measures and performance on the speech perception tasks are reported. RESULTS:
      Differences in performance using the three programming strategies were not large.
      Peak-to-peak amplitude of the ACC was not found to be sensitive enough to
      accurately predict the programming strategy that resulted in the best performance
      on either measure of speech perception. All 10 Hybrid CI users had residual low
      frequency acoustic hearing. For all 10 subjects, allowing them to use both the
      acoustic and electrical signals provided by the implant improved performance on
      the consonant recognition task. For most subjects, it also resulted in slightly
      larger cortical change responses. However, the impact that listening mode had on
      the cortical change responses was small, and again, the correlation between the
      evoked potential and speech perception results was not significant. CONCLUSIONS:
      CAEPs can be successfully measured from Hybrid CI users. The responses that are
      recorded are similar to those recorded from normal-hearing listeners. The goal of
      this study was to see if CAEPs might play a role either in identifying the
      experimental program that resulted in best performance on a consonant recognition
      task or in documenting benefit from the use of the electrical signal provided by
      the Hybrid CI. At least for the stimuli and specific methods used in this study,
      no such predictive relationship was found.

PMID- 26295608
TI  - Cilioretinal Artery Territory Infarction Associated With Papilledema in a Patient
      With Neurofibromatosis Type 2.
AB  - Cilioretinal artery territory infarction can occur in isolation or in association
      with other vascular compromise of the retinal circulation. Our patient, an 18
      year-old woman with neurofibromatosis type 2, developed a cilioretinal artery
      territory infarction in the setting of papilledema. Our case, together with one
      previous report, suggests that cilioretinal artery territory infarction in the
      context of papilledema, although rare, is a real entity. 

PMID- 26295609
TI  - A Retro-Staudinger Cycloaddition: Mechanochemical Cycloelimination of a beta
      Lactam Mechanophore.
AB  - Mechanical activation of a beta-lactam mechanophore using ultrasound induces a
      formal [2 + 2] cycloelimination reaction producing ketene and imine functional
      groups--the reverse reaction of the Staudinger cycloaddition. This transformation
      is predicted by computational modeling and verified by kinetics and UV-vis
      absorption measurements as well as polymer end-group analysis using (1)H and
      (13)C NMR spectroscopy. Addition of the beta-lactam motif to the current
      repertoire of covalent mechanophores coupled with the diverse reactivity of the
      ketene functional group provides a promising new platform for achieving materials
      capable of autonomic self-healing behavior in response to external forces.

PMID- 26295610
TI  - T-cell ligands modulate the cytolytic activity of the CD33/CD3 BiTE antibody
      construct, AMG 330.
AB  - Preclinical and emerging clinical studies demonstrate that bispecific T-cell
      engaging (BiTE) antibody constructs can potently lyse targeted tumor cells, but
      the determinants for their activity remain incompletely understood. Using human
      acute myeloid leukemia (AML) cell lines engineered to overexpress individual T
      cell ligands, we found that expression of the inhibitory ligands, PD-L1 and PD
      L2, reduced the cytolytic activity of the BiTE antibody construct targeting CD33,
      AMG 330; conversely, expression of the activating ligands, CD80 and CD86,
      augmented the cytotoxic activity of AMG 330. Consistent with these findings,
      treatment with an activating antibody directed at the co-stimulatory T-cell
      receptor, CD28, significantly increased AMG 330-induced cytotoxicity in human AML
      cell lines. Using specimens from 12 patients with newly diagnosed or
      relapsed/refractory AML, we found that activation of CD28 also increased the
      activity of AMG 330 in primary human AML cells (P=0.023). Together, our findings
      indicate that T-cell ligands and co-receptors modulate the anti-tumor activity of
      the CD33/CD3 BiTE antibody construct, AMG 330. These findings suggest that such
      ligands/co-receptors could serve as biomarkers of response and that co-treatment
      strategies with pharmacological modulators of T-cell receptor signaling could be
      utilized to further enhance the activity of this targeted therapeutic. 

PMID- 26295611
TI  - Factors influencing extramedullary relapse after allogeneic transplantation for
      multiple myeloma.

PMID- 26295612
TI  - Comparison of Efficacy of Endovascular Aneurysm Repair Versus Open Surgical
      Repair in Middle/High-Risk Patients With Abdominal Aortic Aneurysm.
AB  - To explore the efficacy of endovascular aneurysm repair (EVAR) compared with
      traditional open surgical repair (OSR) in the treatment of middle/high-risk
      patients with abdominal aortic aneurysm (AAA). With a retrospective method, we
      analyzed the clinical data of 57 patients with middle/high-risk AAA admitted to
      Linyi People's Hospital Affiliated to Shandong University from January 2010 to
      January 2014. Twenty-eight of the 57 patients received EVAR and 29 others
      received OSR. Statistical analysis was conducted by the design of spreadsheet
      according to preoperative, intraoperative, perioperative, and postoperative
      follow-up relevant information. Our study showed that the difference in baseline
      characteristics of different therapies in middle/high-risk AAA patients was not
      statistically significant in preoperative period (P > 0.05). In intraoperative
      period, the efficacy of middle/high-risk AAA patients in EVAR group was
      significantly superior to OSR group in terms of blood loss, blood transfusion,
      and general anesthesia rate (all P < 0.01). In perioperative period, the ICU
      observation time and the average fasting time of middle/high-risk AAA patients in
      EVAR group were remarkably lower than OSR group (all P < 0.01), but the average
      hospital stay and the operation cost of middle/high-risk AAA patients in EVAR
      group were notably higher than OSR group. In postoperative follow-up period, OSR
      group was identified with a lower incidence of surgery-related complications than
      EVAR group (P < 0.05), but EVAR group was demonstrated with a higher survival
      rate than OSR group (P < 0.05); after 12 months of follow-up, SF-36 scale scores
      in OSR group were higher than EVAR group (P < 0.05). In conclusion, EVAR may have
      a better short-term effect, whereas OSR may have a better long-term effect in the
      treatment of middle/high-risk AAA patients. 

PMID- 26295613
TI  - Rhabdomyolysis Secondary to Therapeutic Hypothermia After Cardiopulmonary
      Resuscitation: A Rare Complication.
AB  - Patient maintenance after successful cardiopulmonary resuscitation starts with
      decreasing the neurological damage despite serious difficulties such as hypoxic
      ischemic infarcts and reperfusion infarcts. Therapeutic hypothermia is the most
      rejoicing method in use to prevent neurological damage. Here, we discuss about a
      35-year-old woman resuscitated for 20 minutes in hospital who was followed
      because of postpartum cardiomyopathy. Sudden onset of ventricular fibrillation
      subsequent to ventricular tachycardia was the underlying cause of cardiac arrest.
      To prevent neurological damage, therapeutic hypothermia was used, and she was
      cooled for 24 hours. After therapeutic hypothermia, her Glasgow coma score was
      15, fortunately no sequela appeared. Although we were successful to prevent
      neurological damage, rhabdomyolysis arose secondary to therapeutic hypothermia.
      As a result, the intubation process was prolonged, and acute tubular necrosis due
      to myoglobinuria was occurred. Despite all complications patient faced, she was
      discharged on her 31th day; without sequela and with no need for hemodialysis;
      under medical therapy. 

PMID- 26295614
TI  - The Effectiveness of Lamotrigine and Its Blood Levels for Pediatric Epilepsy.
AB  - This study was conducted to evaluate the effectiveness of lamotrigine (LTG) over
      2 years and the usefulness of measuring its blood levels during the follow-up of
      patients with epilepsy. We measured peak blood LTG levels of 32 patients with
      epilepsy (9.16 +/- 3.34 years old; mean +/- SD). The blood levels were measured
      at 6 months, 1 year, and 2 years after reaching the LTG maintenance dosage. The
      effectiveness of LTG was evaluated to determine the seizure reduction rate. The
      patients were classified as effective cases (mean of own seizure reduction rates
      >50%) and ineffective cases (<=50%). The results were that the dosage and blood
      level showed positive correlations in the case of combination use with sodium
      valproate (VPA) (r = 0.690), carbamazepine and/or phenobarbital (r = 0.940), and
      others (r = 0.548). In several groups, the blood levels and efficacies did not
      show any positive correlations. In the cases of combination use with VPA, the
      blood levels of effective cases and ineffective cases were significantly
      different (P = 0.001). The optimal range was 8-11.5 MUg/mL based on the average
      and SD values in the effective cases. No patients had any side effects. In
      conclusion, no precise definition of the therapeutic range was possible because
      of the incomplete correlation between the blood level and seizure frequency. We
      recommend the optimal range of LTG as a therapeutic target without any side
      effects, and it was established that the range in the combination with VPA was 8
      11.5 MUg/mL.

PMID- 26295615
TI  - Radiological study of sachet-packaged water: a case study of the products in Owo
      local government area of Ondo State, Nigeria.
AB  - The radioactivity levels of some sachet-packaged drinking water produced and used
      in Owo, a local government area of Ondo State, Nigeria, were measured. The
      activity concentrations of (226)Ra varied between 0.6   +/-   0.2 Bq L(-1) and
      11.6   +/-   3.2 Bq L(-1) with an arithmetic mean  +/-  standard deviation of 6.6
      +/-   3.6 Bq L(-1), the activity concentrations of (228)Ra varied between 4.5  
      +/-   2.1 Bq L(-1) and 18.6   +/-   6.1 Bq L(-1) with an arithmetic mean  +/- 
      standard deviation of 12.2   +/-   4.5 Bq L(-1) and that of (40)K varied between
      22   +/-   6 Bq L(-1) and 142   +/-   41 Bq L(-1) with an arithmetic mean  +/- 
      standard deviation of 68   +/-   45 Bq L(-1). (40)K was not detected in one
      sample. The resulting annual effective doses due to ingestion of the
      radionuclides (226)Ra and (228)Ra in the water samples varied between 2.4 mSv and
      11.5 mSv with an arithmetic mean  +/-  standard deviation of 7.5   +/-   2.8 mSv,
      which are higher than the recommended standards of WHO and UNSCEAR. Therefore
      this study shows that it is not radiologically advisable to consume any of the
      sachet drinking water studied.

PMID- 26295616
TI  - Work-Function Engineering of Graphene Electrodes by Self-Assembled Monolayers for
      High-Performance Organic Field-Effect Transistors.
AB  - We have devised a method to optimize the performance of organic field-effect
      transistors (OFETs) by controlling the work functions of graphene electrodes by
      functionalizing the surface of SiO2 substrates with self-assembled monolayers
      (SAMs). The electron-donating NH2-terminated SAMs induce strong n-doping in
      graphene, whereas the CH3-terminated SAMs neutralize the p-doping induced by SiO2
      substrates, resulting in considerable changes in the work functions of graphene
      electrodes. This approach was successfully utilized to optimize electrical
      properties of graphene field-effect transistors and organic electronic devices
      using graphene electrodes. Considering the patternability and robustness of SAMs,
      this method would find numerous applications in graphene-based organic
      electronics and optoelectronic devices such as organic light-emitting diodes and
      organic photovoltaic devices. 

PMID- 26295617
TI  - Fingers Crossed: Optical Activity of a Chiral Dimer of Plasmonic Nanorods.
AB  - We investigate theoretically the optical activity of a dimer of plasmonic
      nanoantennas, mimicking the geometry of a molecule with two isolated
      chromophores, a situation commonly described as exciton coupling in organic
      chemistry. As the scale of the system increases and approaches the wavelength of
      visible light, a rich variety of effects arise that are unique to the plasmonic
      case. Scattering of light by the particles, negligible in very small clusters,
      strongly perturbs, and eventually dominates, the optical activity. Additionally,
      retardation effects in dimers with an interparticle separation commensurate with
      the wavelength of the incident light affect the electromagnetic coupling between
      the particles and lead to an asymmetric circular dichroism spectrum. We identify
      conditions for efficient interaction and predict remarkably large anisotropy
      factors. 

PMID- 26295618
TI  - Finding Minimum Structures on the Seam of Crossing in Reactions of Type A + B ->
      X: Exploration of Nonadiabatic Ignition Pathways of Unsaturated Hydrocarbons.
AB  - A new theoretical approach is proposed for finding automatically minimum
      structures on the seam of crossing (MSX) in reactions of type A + B -> X, where
      the artificial-force-induced reaction (AFIR) method is combined with the seam
      model function (SMF) approach. Its application to reactions between triplet
      dioxygen and unsaturated hydrocarbons provided many MSX structures. In addition
      to known ignition pathways, we discovered a pathway through a new type of MSX in
      the reaction of dioxygen with aromatic hydrocarbons; for benzene, this new
      pathway requires a lower energy than those of three known ignition pathways and
      is likely to be the most important. This demonstrates that the AFIR-SMF approach
      has the ability to discover unknown/unexpected MSX structures without prejudice
      for presumed pathways or mechanisms. 

PMID- 26295619
TI  - Employing a Photosynthetic Antenna Complex to Interfacial Electron Transfer on
      ZnO Quantum Dot.
AB  - Photosynthetic antenna complexes exhibit unidirectional energy-transport
      phenomena, which make them potential photosensitizers in interfacial electron
      transfer processes. In the present study, we show the antenna function of
      phycocyanin-allophycocyanin (PC-APC) complex using transient emission and
      absorption spectroscopy. Interfacial electron-transfer dynamics in the PC-APC
      complex sensitized ZnO semiconductor quantum dot material is compared in native
      and denatured conditions. The downhill sequential energy transfer from a
      peripheral phycocyanin disk to a core allophycocyanin disk opens a new electron
      injection pathway from the allophycocyanin disk in addition to primary electron
      injection from directly photoexcited phycocyanin disk. Further, the large
      association of phycocayanobilin chromophores in PC-APC conjugates stabilizes the
      positive charge within the sensitizer, which leads to slower charge recombination
      in comparison to that in denatured condition. This study displays the antenna
      function of energy-efficient biomolecules in favor of better charge separation
      across the semiconductor interface. 

PMID- 26295620
TI  - Role of Molecular Packing in Determining Solid-State Optical Properties of pi
      Conjugated Materials.
AB  - The optical properties of pi-conjugated organic molecules in their solid state
      are critically important in determining performance efficiencies of
      optoelectronic devices such as organic light-emitting diodes and organic thin
      film transistors. This Perspective discusses some recent systematic explorations
      aimed toward arriving at an understanding of the role that molecular packing
      plays in determining these properties. 

PMID- 26295621
TI  - Reactions of Ions with Ionic Liquid Vapors by Selected-Ion Flow Tube Mass
      Spectrometry.
AB  - Room-temperature ionic liquids exert vanishingly small vapor pressures under
      ambient conditions. Under reduced pressure, certain ionic liquids have
      demonstrated volatility, and they are thought to vaporize as intact cation-anion
      ion pairs. However, ion pair vapors are difficult to detect because their
      concentration is extremely low under these conditions. In this Letter, we report
      the products of reacting ions such as NO(+), NH4(+), NO3(-), and O2(-) with
      vaporized aprotic ionic liquids in their intact ion pair form. Ion pair
      fragmentation to the cation or anion as well as ion exchange and ion addition
      processes are observed by selected-ion flow tube mass spectrometry. Free energies
      of the reactions involving 1-ethyl-3-methylimidazolium bis
      trifluoromethylsulfonylimide determined by ab initio quantum mechanical
      calculations indicate that ion exchange or ion addition are energetically more
      favorable than charge-transfer processes, whereas charge-transfer processes can
      be important in reactions involving 1-butyl-3-methylimidazolium dicyanamide. 

PMID- 26295622
TI  - Femtosecond Soft X-ray Spectroscopy of Solvated Transition-Metal Complexes:
      Deciphering the Interplay of Electronic and Structural Dynamics.
AB  - We present the first implementation of femtosecond soft X-ray spectroscopy as an
      ultrafast direct probe of the excited-state valence orbitals in solution-phase
      molecules. This method is applied to photoinduced spin crossover of
      [Fe(tren(py)3)](2+), where the ultrafast spin-state conversion of the metal ion,
      initiated by metal-to-ligand charge-transfer excitation, is directly measured
      using the intrinsic spin-state selectivity of the soft X-ray L-edge transitions.
      Our results provide important experimental data concerning the mechanism of
      ultrafast spin-state conversion and subsequent electronic and structural
      dynamics, highlighting the potential of this technique to study ultrafast
      phenomena in the solution phase. 

PMID- 26295623
TI  - Gold-Substrate-Enhanced Scanning Electron Microscopy of Functionalized Single
      Wall Carbon Nanotubes.
AB  - Functionalized regions of a single-wall carbon nanotube were resolved by scanning
      electron microscopy at 1 kV when the functionalized nanotube was placed on a gold
      substrate. Beam energy and substrate dependence studies suggest that the sharp
      imaging contrast arises from an increase in the yield of secondary electrons as
      compared to gold due to covalent modification of the nanotube. Using this
      surprisingly simple technique, it becomes possible to rapidly map surface
      functionalization on individual carbon nanotubes with a spatial resolution better
      than 10 nm. This new functionalization imaging technique may facilitate spatial
      control of surface chemistry and defect engineering in carbon nanomaterials. 

PMID- 26295624
TI  - Emission Quenching in PbSe Quantum Dot Arrays by Short-Term Air Exposure.
AB  - Clear evidence for two emitting states in PbSe nanocrystals (NCs) has been
      observed. The flow of population between these two states as temperature
      increases is interrupted by the presence of nonradiative trap states correlated
      with the exposure of the NC film to air. Quenching of the higher-energy emission
      begins after only seconds of exposure, with the effect saturating after several
      days. Unlike short-term oxygen-related effects in solution, the emission
      quenching appears to be irreversible, signaling a distinction between surface
      reactivity in NCs in films and that in solution. The origin of the two emissive
      centers and the impact of trapping on other NC film properties (e.g.,
      electron/hole mobilities) remain important issues to be resolved. 

PMID- 26295625
TI  - Hybrid Graphene/Titania Nanocomposite: Interface Charge Transfer, Hole Doping,
      and Sensitization for Visible Light Response.
AB  - We demonstrated for the first time by large-scale ab initio calculations that a
      graphene/titania interface in the ground electronic state forms a charge-transfer
      complex due to the large difference of work functions between graphene and
      titania, leading to substantial hole doping in graphene. Interestingly, electrons
      in the upper valence band can be directly excited from graphene to the conduction
      band, that is, the 3d orbitals of titania, under visible light irradiation. This
      should yield well-separated electron-hole pairs, with potentially high
      photocatalytic or photovoltaic performance in hybrid graphene and titania
      nanocomposites. Experimental wavelength-dependent photocurrent generation of the
      graphene/titania photoanode demonstrated noticeable visible light response and
      evidently verified our ab initio prediction. 

PMID- 26295626
TI  - When a Metastable Oxide Stabilizes at the Nanoscale: Wurtzite CoO Formation upon
      Dealloying of PtCo Nanoparticles.
AB  - Ambient pressure photoelectron and absorption spectroscopies were applied under
      0.2 mbar of O2 and H2 to establish an unequivocal correlation between the surface
      oxidation state of extended and nanosized PtCo alloys and the gas-phase
      environment. Fundamental differences in the electronic structure and reactivity
      of segregated cobalt oxides were associated with surface stabilization of
      metastable wurtzite-CoO. In addition, the promotion effect of Pt in the reduction
      of cobalt oxides was pronounced at the nanosized particles but not at the
      extended foil. 

PMID- 26295627
TI  - Phthalocyanine-Carbon Nanostructure Materials Assembled through Supramolecular
      Interactions.
AB  - The use of self-assembly for the construction of materials based on
      phthalocyanines and carbon nanostructures-fullerenes, single-walled carbon
      nanotubes, and graphene-has demonstrated to be a versatile strategy for the
      preparation of novel, multifunctional systems. Photophysical studies carried out
      on these photo- and electroactive supramolecular ensembles have revealed the
      occurrence of an efficient photoinduced electron-transfer process, thus paving
      the way for the utilization of these materials as active components in
      optoelectronic devices. This Perspective highlights the recent progress in the
      preparation of such materials and the potential use of these systems for the
      construction of nanostructured materials with singular physicochemical
      properties. 

PMID- 26295628
TI  - Surfactants Possessing Multiple Polar Heads. A Perspective on their Unique
      Aggregation Behavior and Applications.
AB  - Surfactants containing more than one head group are known to exhibit a wide range
      of interesting properties as they undergo aggregation in water. The correlation
      between the molecular structure of these surfactants and their properties (for
      example, critical micellar concentration, aggregation number, morphology,
      counterion dissociation, fractional charge, etc.) can provide useful information
      to define the structure-activity relationship. The influence of the number of
      head groups on the surfactant aggregation is further evident from interesting
      interfacial behavior, seen in biological applications. This Perspective
      highlights recent trends in surfactant aggregation effects and focuses on
      emerging challenges in the field. 

PMID- 26295629
TI  - High Surface Area, sp(2)-Cross-Linked Three-Dimensional Graphene Monoliths.
AB  - Developing three-dimensional (3D) graphene assemblies with properties similar to
      those individual graphene sheets is a promising strategy for graphene-based
      electrodes. Typically, the synthesis of 3D graphene assemblies relies on van der
      Waals forces for holding the graphene sheets together, resulting in bulk
      properties that do not reflect those reported for individual graphene sheets.
      Here, we report the use of sol-gel chemistry to introduce chemical bonding
      between the graphene sheets and control the bulk properties of graphene-based
      aerogels. Adjusting synthetic parameters allows a wide range of control over
      surface area, pore volume, and pore size, as well as the nature of the chemical
      cross-links (sp(2) vs sp(3)). The bulk properties of the graphene-based aerogels
      represent a significant step toward realizing the properties of individual
      graphene sheets in a 3D assembly with surface areas approaching the theoretical
      value of an individual sheet. 

PMID- 26295630
TI  - Design and Optical Properties of Active Polymer-Coated Plasmonic Nanostructures.
AB  - The grafting of stimuli-responsive polymer brushes on plasmonic structures
      provides a perfectly controlled two-dimensional active device with optical
      properties that can be modified through external stimuli. Herein, we demonstrate
      thermally induced modifications of the plasmonic response of lithographic gold
      nanoparticles functionalized by thermosensitive polymer brushes of (poly(N
      isopropylacrylamide), PNIPAM). Optical modifications result from refractive local
      index changes due to a phase transition from a hydrophilic state (swollen regime)
      to a hydrophobic state (collapsed regime) of the polymer chains occurring in a
      very small range of temperatures. The refractive index of the polymer in aqueous
      solution is estimated in both states, deduced from the discrete dipole
      approximation (DDA) method. The combination of lithographic gold NPs and
      thermoresponsive polymer chains leads to a new generation of perfectly calibrated
      and dynamically controlled hybrid gold/polymer system for real-time nanosensors. 

PMID- 26295631
TI  - Self-Assembled Organic Aggregates.

PMID- 26295632
TI  - Open-Access Institutional Repositories: An Evolving Process?

PMID- 26295634
TI  - MRI of Labral and Chondral Lesions of the Hip.
AB  - OBJECTIVE: Unenhanced MRI, indirect MR arthrography, and direct MR arthrography
      have been used in the radiologic evaluation of patients with suspected labral
      tears and chondral lesions of the hip. The purpose of this article is to examine
      the existing evidence for the use of these techniques in patients with hip pain
      and suspected labral or chondral abnormalities. CONCLUSION: Evidence from a
      review of the radiologic literature supports the use of direct MR arthrography
      over unenhanced MRI and indirect MR arthrography for the detection of labral and
      cartilage abnormalities in the hip. Although high-resolution unenhanced 3-T MRI
      appears promising, limited information in the literature supports its use in the
      detection and characterization of chondrolabral lesions.

PMID- 26295633
TI  - Prospective Cohort Study of Nephrogenic Systemic Fibrosis in Patients With Stage
      3-5 Chronic Kidney Disease Undergoing MRI With Injected Gadobenate Dimeglumine or
      Gadoteridol.
AB  - OBJECTIVE: The purpose of this study was to determine the incidence of
      nephrogenic systemic fibrosis (NSF) in patients with chronic kidney disease (CKD)
      and moderate-to-severe impairment of kidney function who had not previously been
      exposed to gadolinium-based contrast agents (GBCAs) or referred to undergo
      contrast-enhanced MRI with gadobenate dimeglumine or gadoteridol. SUBJECTS AND
      METHODS: Two multicenter prospective cohort studies evaluated the incidence of
      unconfounded NSF in patients with stage 3 CKD (estimated glomerular filtration
      rate [eGFR] in cohort 1, 30-59 mL/min/1.73 m(2)) or stage 4 or 5 CKD (eGFR in
      cohort 2, < 30 mL/min/1.73 m(2)) after injection of gadobenate dimeglumine (study
      A) or gadoteridol (study B). A third study (study C) determined the incidence of
      NSF in patients with stage 4 or 5 CKD who had not received a GBCA in the 10 years
      before enrollment. Monitoring for signs and symptoms suggestive of NSF was
      performed via telephone at 1, 3, 6, and 18 months, with clinic visits occurring
      at 1 and 2 years. RESULTS: For studies A and B, the populations evaluated for NSF
      comprised 363 and 171 patients, respectively, with 318 and 159 patients in cohort
      1 of each study, respectively, and with 45 and 12 patients in cohort 2,
      respectively. No signs or symptoms of NSF were reported or detected during the 2
      years of patient monitoring. Likewise, no cases of NSF were reported for any of
      the 405 subjects enrolled in study C. CONCLUSION: To our knowledge, and
      consistent with reports in the literature, no association of gadobenate
      dimeglumine or gadoteridol with unconfounded cases of NSF has yet been
      established. Study data confirm that both gadoteridol and gadobenate dimeglumine
      properly belong to the class of GBCAs considered to be associated with the lowest
      risk of NSF.

PMID- 26295635
TI  - Scapular Fractures: What Radiologists Need to Know.
AB  - OBJECTIVE: The purpose of this article are to review scapular anatomy and
      function, describe imaging features of traumatic scapular injury, and discuss the
      role of diagnostic imaging in clinical decision making after shoulder trauma.
      CONCLUSION: Knowledge of scapular anatomy, function, injury patterns, imaging
      appearance, and clinical management is important for the radiologist to the care
      of patients who present with acute shoulder trauma.

PMID- 26295636
TI  - Regional Articular Cartilage Abnormalities of the Hip.
AB  - OBJECTIVE: Imaging of hip cartilage is challenging because of its limited
      thickness and complex geometry and therefore requires advanced MRI techniques.
      However, cartilage abnormalities are found in a number of disease entities, and
      their diagnosis may impact patient management. This article will provide
      pertinent information about the motivation to image hip cartilage, which imaging
      techniques to use, and how to analyze cartilage; finally, we will discuss disease
      entities with regional cartilage lesions, including the typical MRI findings.
      CONCLUSION: Because the detection and quantification of regional cartilage
      abnormalities are critical for guidance of operative and nonoperative management
      of hip disorders, radiologists should be familiar with imaging and analysis
      techniques for assessing hip cartilage.

PMID- 26295637
TI  - Tip-of-the-Iceberg Fractures: Small Fractures That Mean Big Trouble.
AB  - OBJECTIVE: Several small and seemingly unimportant fractures are associated with
      other more serious injuries, usually to adjacent soft tissues. The purpose of
      this article is to discuss 11 of these injuries, in each case describing the
      fracture (the tip) and the injuries that lie beneath the surface (the iceberg).
      CONCLUSION: Some fractures should be considered analogous to the tip of an
      iceberg. Their recognition is important because the commonly associated injuries,
      which are often more serious than the fracture itself, are typically not evident
      on radiographs and require advanced imaging for accurate diagnosis and treatment.

PMID- 26295638
TI  - Comparison of Low-Dose Higher-Relaxivity and Standard-Dose Lower-Relaxivity
      Contrast Media for Delayed-Enhancement MRI: A Blinded Randomized Crossover Study.
AB  - OBJECTIVE: The gadolinium-based MRI contrast agent gadobenate dimeglumine has
      nearly twice the MR relaxivity of gadopentetate dimeglumine at 1.5 T. The purpose
      of this study was to determine whether a lower dose (0.1 mmol/kg) of gadobenate
      dimeglumine can be used to obtain delayed-enhancement MR images comparable to
      those obtained with a standard dose (0.2 mmol/kg) of gadopentetate dimeglumine.
      SUBJECTS AND METHODS: In this blinded randomized crossover study, 20 patients
      with known myocardial infarction underwent two separate delayed-enhancement MRI
      examinations after receiving 0.1 mmol/kg gadobenate dimeglumine and 0.2 mmol/kg
      gadopentetate dimeglumine (random administration). The conspicuity of lesion
      enhancement 5, 10, and 20 minutes after contrast administration was quantified as
      relative enhancement ratio (RER). RESULTS: With either gadolinium-based contrast
      agent, damaged myocardium had higher signal intensity than normal remote
      myocardium (RER > 4) on delayed-enhancement MR images, and the blood RER declined
      over time after contrast administration. The blood RER was not significantly
      higher for gadobenate dimeglumine than for gadopentetate dimeglumine at 5 and 10
      minutes. Nevertheless, there was a larger reduction in blood RER for gadobenate
      dimeglumine than for gadopentetate dimeglumine between 5 and 10 minutes and
      between 10 and 20 minutes. The volumes of enhancement were similar for gadobenate
      dimeglumine (13.6 +/- 8.8 cm(3)) and gadopentetate dimeglumine (13.5 +/- 8.9
      cm(3)) (p = 0.98). The mean difference in Bland-Altman analysis for delayed
      enhancement volume between the agents was 0.1 cm(3). CONCLUSION: Qualitatively
      and quantitatively, delayed-enhancement MR images of ischemic myocardium obtained
      with 0.1 mmol/kg gadobenate dimeglumine are comparable to those obtained with 0.2
      mmol/kg gadopentetate dimeglumine 5, 10, and 20 minutes after contrast
      administration.

PMID- 26295639
TI  - Relationship Between Emphysema Severity and the Location of Lung Cancer in
      Patients With Chronic Obstructive Lung Disease.
AB  - OBJECTIVE: New phenotypes of chronic obstructive pulmonary disease (COPD) based
      on emphysema severity have been recognized recently. The purpose of this study
      was to determine the relationship between emphysema severity (phenotype) and lung
      cancer location in patients with COPD. MATERIALS AND METHODS: Four hundred
      patients with 405 primary lung cancers confirmed pathologically between January
      2010 and March 2014 were included in the study. Of these, 193 patients received a
      diagnosis of COPD according to the Global Initiative for Chronic Obstructive Lung
      Disease guidelines. We scored emphysema severity (0-4) on thin-section CT and
      assigned the anatomic tumor location of lung cancer as peripheral or central.
      RESULTS: Patients with COPD had a higher proportion of centrally located lung
      cancer compared with those without COPD (36.4% vs 17.4%; p < 0.001). In patients
      with COPD, lower emphysema grades (odds ratio [OR], 0.69; 95% CI, 0.51-0.93; p =
      0.016) and reduced ratio of forced expiratory volume in 1 second (FEV1) to forced
      vital capacity (FVC) (OR, 0.94; 95% CI, 0.89-0.99; p = 0.024) were associated
      with central location. After adjusting for age, smoking, and spirometry results,
      the proportion of central location was approximately four times higher in
      patients with lower emphysema grades (0-2, < 25%) than in those with severe
      grades (grade 4, > 51%). CONCLUSION: Lower emphysema grades and reduced FEV1/FVC
      seemed to be independent predictors of central location of lung cancer in COPD.
      Therefore, in patients with COPD with lower grade emphysema and airway
      predominant disease, additional screening tools may have to be considered for
      central lung cancer detection along with thin-section CT.

PMID- 26295640
TI  - Gadoxetate Disodium-Enhanced MRI to Differentiate Dysplastic Nodules and Grade of
      Hepatocellular Carcinoma: Correlation With Histopathology.
AB  - OBJECTIVE: The objective of our study was to determine quantitative differences
      to differentiate low-grade from high-grade dysplastic nodules (DNs) and low-grade
      from high-grade hepatocellular carcinomas (HCCs) using gadoxetate disodium
      enhanced MRI. MATERIALS AND METHODS: A retrospective study of 149 hepatic nodules
      in 127 consecutive patients who underwent gadoxetic acid-enhanced MRI was
      performed. MRI signal intensities (SIs) of the representative lesion ROI and of
      ROIs in liver parenchyma adjacent to the lesion were measured on unenhanced T1
      weighted imaging and on dynamic contrast-enhanced MRI in the arterial, portal
      venous, delayed, and hepatobiliary phases. The relative SI of the lesion was
      calculated for each phase as the relative intensity ratio as follows: [mass SI /
      liver SI]. RESULTS: Of the 149 liver lesions, nine (6.0%) were low-grade DNs, 21
      (14.1%) were high-grade DNs, 83 (55.7%) were low-grade HCCs, and 36 (24.2%) were
      high-grade HCCs. The optimal cutoffs for differentiating low-grade DNs from high
      grade DNs and HCCs were an unenhanced to arterial SI of >= 0 or a relative SI on
      T2-weighted imaging of <= 1.5, with a positive predictive value (PPV) of 99.2%
      and accuracy of 88.6%. The optimal cutoffs for differentiating low-grade HCCs
      from high-grade HCCs were a relative hepatobiliary SI of <= 0.5 or a relative T2
      SI of >= 1.5, with a PPV of 81.0% and an accuracy of 60.5%. CONCLUSION:
      Gadoxetate disodium-enhanced MRI allows quantitative differentiation of low-grade
      DNs from high-grade DNs and HCCs, but significant overlap was seen between low
      grade HCCs and high-grade HCCs.

PMID- 26295641
TI  - Imaging Features of Various Adrenal Neoplastic Lesions on Radiologic and Nuclear
      Medicine Imaging.
AB  - OBJECTIVE: The purpose of this review is to describe the features of diverse
      adrenal neoplastic lesions on radiologic and nuclear medicine imaging.
      CONCLUSION: Various neoplastic lesions with or without malignant potential can
      occur in the adrenal gland. Knowledge of imaging features of adrenal lesions on
      radiologic and nuclear medicine imaging will facilitate differential diagnosis
      and assessment of malignant potential.

PMID- 26295642
TI  - Use of MRI for Lobar Classification of Benign Prostatic Hyperplasia: Potential
      Phenotypic Biomarkers for Research on Treatment Strategies.
AB  - OBJECTIVE: We present an MRI classification of benign prostatic hyperplasia (BPH)
      for use as a phenotype biomarker in the study of proposed therapeutic
      interventions. CONCLUSION: Six patterns of BPH distribution were identified.
      Illustrations are provided for each classification type.

PMID- 26295643
TI  - A Survey of Radiation Doses in CT Urography Before and After Implementation of
      Iterative Reconstruction.
AB  - OBJECTIVE: The purpose of this study was to survey the radiation dose used in CT
      urography (CTU) in routine clinical practice, both before and after
      implementation of a scanning protocol that uses iterative reconstruction
      (Adaptive Iterative Dose Reduction 3D [AIDR 3D]). MATERIALS AND METHODS: We
      retrospectively surveyed dose reports from consecutive CTU examinations performed
      in 2011 with the use of 64- and 320-MDCT scanners that were reconstructed with
      filtered back projection (FBP) and from CTU examinations performed from May 2012
      through November 2013 that were reconstructed with the use of AIDR 3D. Findings
      from these dose reports were then correlated with such patient characteristics as
      weight and body mass index (BMI; weight in kilograms divided by the square of
      height in meters). Only dose reports from single-bolus three-phase CTU
      examinations were included in the study. The volume CT dose index, dose-length
      product (DLP), and effective dose were surveyed both per examination and per
      phase by use of published effective dose DLP conversion factors. Image quality
      was evaluated subjectively for a subset of patients. RESULTS: The two study
      cohorts included 82 patients (median patient weight, 75.0 kg; median BMI, 25.3)
      who underwent CTU with FBP and 85 patients (median patient weight, 78.0 kg;
      median BMI, 24.5) who underwent CTU with AIDR 3D. The median total DLP and median
      effective dose were 924 mGy . cm and 13.0 mSv, respectively, in the CTU with the
      FBP cohort and 433 mGy . cm and 6.1 mSv, respectively, in the CTU with the AIDR
      3D cohort. The median DLP in the unenhanced, nephrogenic, and excretory phases
      was 218, 300, and 441 mGy . cm, respectively, in patients undergoing CTU with FBP
      and 114, 121, and 190 mGy . cm, respectively, in patients undergoing CTU with
      AIDR 3D. Image quality was diagnostic in both groups, with relatively fewer
      artifacts noted on scans obtained using CTU with AIDR 3D. CONCLUSION: Our study
      presents detailed dose data from three-phase CTU examinations performed both
      before and after implementation of iterative reconstruction. Implementation of a
      CTU protocol using iterative reconstruction resulted in a mean effective dose of
      6.1 mSv with preservation of clinical diagnostic image quality.

PMID- 26295644
TI  - CT-Guided Transgluteal Biopsy for Systematic Random Sampling of the Prostate in
      Patients Without Rectal Access.
AB  - OBJECTIVE: The objective of our study was to review our experience with CT-guided
      transgluteal prostate biopsy in patients without rectal access. MATERIALS AND
      METHODS: Twenty-one CT-guided transgluteal prostate biopsy procedures were
      performed in 16 men (mean age, 68 years; age range, 60-78 years) who were under
      conscious sedation. The mean prostate-specific antigen (PSA) value was 11.4 ng/mL
      (range, 2.3-39.4 ng/mL). Six had seven prior unsuccessful transperineal or
      transurethral biopsies. Biopsy results, complications, sedation time, and
      radiation dose were recorded. The mean PSA values and number of core specimens
      were compared between patients with malignant results and patients with
      nonmalignant results using the Student t test. RESULTS: The average procedural
      sedation time was 50.6 minutes (range, 15-90 minutes) (n = 20), and the mean
      effective radiation dose was 8.2 mSv (median, 6.6 mSv; range 3.6-19.3 mSv) (n =
      13). Twenty of the 21 (95%) procedures were technically successful. The only
      complication was a single episode of gross hematuria and penile pain in one
      patient, which resolved spontaneously. Of 20 successful biopsies, 8 (40%) yielded
      adenocarcinoma (Gleason score: mean, 8; range, 7-9). Twelve biopsies yielded
      nonmalignant results (60%): high-grade prostatic intraepithelial neoplasia (n =
      3) or benign prostatic tissue with or without inflammation (n = 9). Three
      patients had carcinoma diagnosed on subsequent biopsies (second biopsy, n = 2
      patients; third biopsy, n = 1 patient). A malignant biopsy result was not
      significantly associated with the number of core specimens (p = 0.3) or the mean
      PSA value (p = 0.1). CONCLUSION: CT-guided transgluteal prostate biopsy is a safe
      and reliable technique for the systematic random sampling of the prostate in
      patients without a rectal access. In patients with initial negative biopsy
      results, repeat biopsy should be considered if there is a persistent rise in the
      PSA value.

PMID- 26295645
TI  - Impact of a Structured Report Template on the Quality of MRI Reports for Rectal
      Cancer Staging.
AB  - OBJECTIVE: The purpose of this study is to assess the impact of implementing a
      structured report template on the quality of MRI reports for rectal cancer
      staging. MATERIALS AND METHODS: After excluding examinations performed after
      surgery or neoadjuvant therapy, we analyzed all rectal cancer staging MRI reports
      finalized at an academic medical center 12 months before and after an
      intervention consisting of implementing a structured report template integrated
      into the institution's speech recognition system. The primary outcome measure was
      the quality of rectal cancer staging MRI reports classified as optimal,
      satisfactory, or unsatisfactory, on the basis of the documentation of 14 quality
      measures predefined by a consensus of the institution's abdominal radiology
      subspecialists. Chi-square and t tests were used to assess differences in report
      quality and documentation of each discrete quality measure before and after the
      intervention. RESULTS: The study cohort included 106 MRI reports from 104
      patients (mean age, 60 years; 58.5% male); 52 (49.1%) of the reports were
      completed before implementation of the structured report template. After
      implementation, the proportion of total reports classified as optimal or
      satisfactory increased from 38.5% (20/52) to 70.4% (38/54) (p = 0.0010). No
      reports generated before the intervention were classified as optimal, whereas
      40.7% (22/54) of reports were classified as optimal after the intervention.
      CONCLUSION: Implementation and voluntary use of a structured report template
      improved the quality of MRI reports for rectal cancer staging compared with free
      text format.

PMID- 26295646
TI  - Reviewing CT Scout Images: Observations of an Expert Witness.
AB  - OBJECTIVE: The purpose of this article is to share the views of an experienced
      expert witness in medical malpractice cases on the use of CT scout images.
      CONCLUSION: The medical literature has resurrected issues regarding viewing of CT
      scout images. Scout images are an integral part of any CT examination and should
      be carefully reviewed for findings that may or may not be included in the FOV of
      the study.

PMID- 26295647
TI  - Estimated Patient Dose Indexes in Adult and Pediatric MDCT: Comparison of
      Automatic Tube Voltage Selection With Fixed Tube Current, Fixed Tube Voltage, and
      Weight-Based Protocols.
AB  - OBJECTIVE: The purposes of this study were to determine the differences in
      estimated volumetric CT dose index (CTDIvol) obtained from the topogram before
      abdominal and pelvic MDCT in adult and pediatric patients using a scan type-based
      algorithm for selecting kilovoltage (CARE kV) and a fixed and a weight-based
      Quality Reference mAs for selecting tube (gmAs) current-exposure time product, in
      comparison with standard protocols, and to determine the bias and variability of
      estimated CTDIvol vis-a-vis actual CTDIvol using the standard protocols.
      MATERIALS AND METHODS: During a 14-month period, 312 adult and pediatric patients
      referred for abdominal and pelvic MDCT were included in the study. For all
      patients, the estimated CTDIvol based on the topogram was recorded: protocol A,
      CARE kV on and 210 gmAs; protocol B, CARE kV on and 1 gmAs times patient weight
      (in pounds); and protocol C (standard protocol), CARE kV off, 120 kVp, and 1 gmAs
      times patient weight (in pounds). For the pediatric patients, estimated CTDIvol
      for the standard protocol D was calculated with 120 kVp and 150 gmAs. All
      patients were scanned with the standard protocols, and the actual CTDIvol was
      recorded. Linear regression models compared the CTDIvol of the three protocols in
      adults and the fourth for children. The estimated and actual CTDIvol were
      compared using a t test. RESULTS: Protocol B yielded the lowest estimated CTDIvol
      (mean, 13.2 mGy for adults and 3.5 mGy for pediatric patients). The estimated
      CTDIvol overestimated the actual CTDIvol by, on average, 1.07 mGy for adults and
      0.3 mGy for children. CONCLUSION: CARE kV appears to reduce estimated CTDIvol vis
      a-vis standard protocols only when a weight-based gmAs is used. Prescan estimated
      CTDIvol calculations appear to generally overestimate actual CTDIvol.

PMID- 26295648
TI  - Estimation of Organ and Effective Doses for Neonate and Infant Diagnostic Cardiac
      Catheterizations.
AB  - OBJECTIVE: Radiation exposure to neonates and infants during cardiac
      catheterizations is an important issue. Smaller patient size and higher heart
      rate in these patients result in a greater need for magnification modes and
      higher frame rates, all of which contribute to a significant increase in
      radiation doses. The aims of our study were to evaluate organ and effective doses
      for neonates and infants during diagnostic cardiac catheterizations on the basis
      of in-phantom dosimetry and conversion factors from dose-area product (DAP) to
      the effective dose. MATERIALS AND METHODS: Organ doses for 0- and 1-year-old
      children during diagnostic cardiac catheterizations were measured by
      radiophotoluminescence glass dosimeters implanted in neonate and infant
      anthropomorphic phantoms. The effective doses were evaluated according to
      recommendations of the International Commission on Radiologic Protection (ICRP)
      publication 103. RESULTS: The mean effective doses evaluated according to ICRP
      103 were 7.7 mSv (range, 0.1-18.4 mSv) for a neonate and 7.3 mSv (range, 1.9-18.6
      mSv) for an infant. Conversion factors from DAP to the effective dose were 2.2
      and 4.0 in posteroanterior and lateral cine angiography, respectively, for a
      neonate and 1.4 and 2.7 in posteroanterior and lateral cine angiography,
      respectively, for an infant. CONCLUSION: The dose data and conversion factors
      evaluated in this study could be useful for the estimation of radiation exposure
      in neonates and infants during diagnostic cardiac catheterization.

PMID- 26295649
TI  - Imaging of Nervous System Involvement in Hematologic Malignancies: What
      Radiologists Need to Know.
AB  - OBJECTIVE: The purpose of this article is to provide a comprehensive review of
      the imaging features of neurologic involvement in hematologic malignancies.
      CONCLUSION: Neurologic involvement can be seen in lymphoma, leukemia, post
      transplant lymphoproliferative disorder (PTLD), plasma cell neoplasms, and
      histiocytic and dendritic neoplasms. Imaging, MRI in particular, plays an
      important role in the workup of these patients. Familiarity with the imaging
      features of nervous system involvement in hematologic malignancies can help
      radiologists suggest the diagnosis and guide management.

PMID- 26295650
TI  - Iterative Reconstruction Leads to Increased Subjective and Objective Image
      Quality in Cranial CT in Patients With Stroke.
AB  - OBJECTIVE: The purpose of this study was to determine whether iterative
      reconstruction improves the quality of cranial CT (CCT) images of stroke
      patients. MATERIALS AND METHODS: Fifty-one CCT studies of patients with
      infarction performed with either a low (260 mAs; n = 21) or standard (340 mAs; n
      = 30) dose were reconstructed with both filtered back projection (FBP) and
      sinogram-affirmed iterative reconstruction (SAFIRE) with five strength levels (S1
      S5). The resulting six image sets (one FBP and one each for SAFIRE levels S1-S5)
      were rated separately by two blinded radiologists in terms of conspicuity of
      infarcted areas on a 5-point scale. Noise and infarct-to-normal brain as well as
      medullary-to-cortical contrast-to-noise ratios (CNRs) were measured. Ratings,
      noise, and CNRs were intraindividually compared within the same dose group
      (Fisher exact test) and interindividually between the different dose groups
      (Wilcoxon-Mann-Whitney U test). RESULTS: The strength level S4 showed the best
      conspicuity of infarcted areas. Compared with FBP, SAFIRE S4 statistically
      significantly (p < 0.01) reduced noise and improved CNRs without statistically
      significant differences in all subjective and objective criteria (p > 0.01) when
      the dose was reduced. Patients examined with a 260-mAs low-dose were exposed to a
      statistically significantly lower dose (1.77 vs 2.33 mSv; p < 0.01). CONCLUSION:
      Iterative reconstruction (SAFIRE at strength level S4) leads to increased
      subjective and objective image quality in CCT and allows dose reduction (-24%)
      without losses in the demarcation of ischemic lesions.

PMID- 26295651
TI  - Volume-Based Assessment With 18F-FDG PET/CT Improves Outcome Prediction for
      Patients With Stage IIIA-N2 Non-Small Cell Lung Cancer.
AB  - OBJECTIVE: We evaluated the prognostic impact of volume-based assessment by
      pretreatment (18)F-FDG PET/CT in patients who had clinical stage IIIA-N2 non
      small cell lung cancer (NSCLC) treated with neoadjuvant concurrent
      chemoradiotherapy (CCRT) followed by surgical resection. MATERIALS AND METHODS:
      We reviewed 161 consecutive patients who had stage IIIA-N2 NSCLC treated with
      neoadjuvant CCRT followed by surgery. In all cases, N2 disease was pathologically
      confirmed by mediastinoscopic biopsy, endobronchial ultrasound-guided
      transbronchial needle aspiration, or video-assisted thoracoscopic surgery. We
      measured the total metabolic tumor volume (total MTV) and the maximum
      standardized uptake value (SUVmax), including a primary tumor and metastatic
      nodes on the pretreatment scan. Overall survival (OS) and disease-free survival
      (DFS) were assessed using the Kaplan-Meier method. The association of PET
      parameters with OS and DFS was determined by univariable and multivariable
      analyses performed using the Cox regression model. RESULTS: A higher total MTV
      was significantly associated with poor DFS (hazard ratio [HR], 1.82; p = 0.036)
      and OS (HR = 2.97; p = 0.012) in the multivariable analysis. In contrast, a
      higher SUVmax was not significantly associated with poor DFS and OS. Patients
      with a high total MTV (> 22 cm(3)) had a median survival time that was
      significantly shorter than that of patients with a low total MTV (median DFS,
      11.3 vs 42.0 months, respectively [p < 0.001]; median OS, 38.3 months vs not
      reached [p < 0.001]). Kaplan-Meier curves showed significant differences on the
      basis of total MTV in patients with or without mediastinal downstaging after
      CCRT. Patients with a high total MTV had significantly worse DFS when they had
      post-neoadjuvant pathologic (yp) stage 0-II disease (p = 0.020) or yp stage III
      disease (p = 0.036). Higher total MTV was also associated with worse OS in
      patients with yp stage 0-II disease (p = 0.013) or yp stage III disease (p =
      0.007). CONCLUSION: A higher pretreatment total MTV is associated with worse
      outcome, independent of yp stage, in patients with stage IIIA-N2 NSCLC treated
      with neoadjuvant CCRT followed by surgery.

PMID- 26295652
TI  - Diagnostic Accuracy of Follow-Up FDG PET or PET/CT in Patients With Head and Neck
      Cancer After Definitive Treatment: A Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: The purpose of this study was to assess the diagnostic performance of
      FDG PET or PET/CT for detection of local, regional, and distant recurrences in
      the follow-up of patients with head and neck cancer who underwent definitive
      treatment. MATERIALS AND METHODS: A systematic search was performed in MEDLINE
      and Cochrane Library (updated September 2014) to identify relevant published
      studies. Studies investigating the accuracy of FDG PET/CT that were performed at
      least 4 months after therapy were included. Two authors independently screened
      all retrieved articles, selected studies that met the inclusion criteria, and
      extracted the data. Histopathologic confirmation or clinical follow-up of at
      least 6 month (or both) was considered as the reference standard. RESULTS: Twenty
      three studies constituting a total of 2247 FDG PET/CT examinations met our
      inclusion criteria. The pooled sensitivity and specificity of follow-up PET/CT
      for detection of recurrence were 0.92 (95% CI, 0.90-0.94), and 0.87 (95% CI, 0.82
      0.91), respectively. The pooled sensitivity and specificity of scans performed 4
      12 months after treatment were 0.95 (95% CI, 0.91-0.97) and 0.78 (95% CI, 0.70
      0.84), respectively. Similar estimates for scans performed at or more than 12
      months after treatment were 0.92 (95% CI, 0.85-0.96) and 0.91 (95% CI, 0.78
      0.96), respectively. The overall accuracy of FDG PET/CT in detecting recurrence
      is higher in patients without suspicion of recurrence before the scan compared
      with the patients with suspected recurrence. CONCLUSION: The high diagnostic
      performance of FDG PET/CT in detecting recurrence in curatively treated patients
      with head and neck cancer supports its use in clinical practice for patient
      follow-up. Further studies are needed to evaluate the prognostic utility of
      PET/CT in the follow-up of head and neck cancer.

PMID- 26295653
TI  - Distinguishing Osteomyelitis From Ewing Sarcoma on Radiography and MRI.
AB  - OBJECTIVE: The purpose of this study was to determine whether clinical and
      imaging features can distinguish osteomyelitis from Ewing sarcoma (EWS) and to
      assess the accuracy of percutaneous biopsy versus open biopsy in the diagnosis of
      these diseases. MATERIALS AND METHODS: Three radiologists reviewed the
      radiographs and MRI examinations of 32 subjects with osteomyelitis and 31
      subjects with EWS to determine the presence of 36 imaging parameters. Information
      on demographic characteristics, history, physical examination findings,
      laboratory findings, biopsy type, and biopsy results were recorded. Individual
      imaging and clinical parameters and combinations of these parameters were tested
      for correlation with findings from histologic analysis. The diagnostic accuracy
      of biopsy was also determined. RESULTS: On radiography, the presence of joint or
      metaphyseal involvement, a wide transition zone, a Codman triangle, a periosteal
      reaction, or a soft-tissue mass, when tested individually, was more likely to be
      noted in subjects with EWS (p <= 0.05) than in subjects with osteomyelitis. On
      MRI, permeative cortical involvement and soft-tissue mass were more likely in
      subjects with EWS (p <= 0.02), whereas a serpiginous tract was more likely to be
      seen in subjects with osteomyelitis (p = 0.04). African Americans were more
      likely to have osteomyelitis than EWS (p = 0). According to the results of
      multiple regression analysis, only ethnicity and soft-tissue mass remained
      statistically significant (p <= 0.01). The findings from 100% of open biopsies
      (18/18) and 58% of percutaneous biopsies (7/12) resulted in the diagnosis of
      osteomyelitis, whereas the findings from 88% of open biopsies (22/25) and 50% of
      percutaneous biopsies (3/6) resulted in a diagnosis of EWS. CONCLUSION: Several
      imaging features are significantly associated with either EWS or osteomyelitis,
      but many features are associated with both diseases. Other than ethnicity, no
      clinical feature improved diagnostic accuracy. Compared with percutaneous biopsy,
      open biopsy provides a higher diagnostic yield but may be inconclusive,
      especially for cases of EWS. Our findings underscore the need for better methods
      of diagnosing these disease processes.

PMID- 26295654
TI  - Qualitative FDG PET Image Assessment Using Automated Three-Segment MR Attenuation
      Correction Versus CT Attenuation Correction in a Tertiary Pediatric Hospital: A
      Prospective Study.
AB  - OBJECTIVE: The purpose of this study was to systematically evaluate the
      diagnostic quality of (18)F-FDG PET images generated using MR attenuation
      correction (MRAC) compared with those images generated using CT attenuation
      correction (CTAC) in a pediatric population. SUBJECTS AND METHODS: Forty-two
      patients (mean age, 12.8 years; percentage who were male, 57%) who were referred
      for 62 indicated whole-body PET/CT studies were prospectively recruited to
      undergo PET/MRI examinations during the same clinic visit in which PET/CT was
      performed. MRAC was performed using an automatic three-segment model. Three
      nuclear radiologists scored the diagnostic quality of the PET images generated by
      MRAC and CTAC using a Likert scale (range of scores, 1-5). Images graded with a
      score of 1-3 were considered clinically unacceptable, whereas images with a score
      of 4-5 were considered clinically acceptable. A Wilcoxon signed-rank test was
      used to compare differences in the grading of PET/MRI and PET/CT images. The
      Fisher exact test was used to evaluate potential differences in clinically
      acceptable image quality and the presence of artifact. Fleiss kappa statistics
      were used to examine interobserver agreement. RESULTS: There was no statistically
      significant difference in the proportion of PET images generated with MRAC and
      CTAC for which image quality was considered clinically acceptable. A total of
      3.9% of PET assessments generated with MRAC were of unacceptable image quality,
      compared with 2.2% of PET images generated with CTAC. Two of the three
      radiologists who reviewed the PET images reported the presence of artifacts more
      often on MRAC-derived images, and they graded the mean quality of these images
      0.48 and 0.29 points lower on the 5-point Likert scale than they graded the mean
      quality of CTAC-derived images (p < 0.0001). Interobserver agreement was fair
      (kappa = 0.39). CONCLUSION: The diagnostic quality of PET images obtained from a
      pediatric population with the use of an automatic three-segmentation MRAC method
      was comparable to that of PET images obtained with the use of CTAC.

PMID- 26295655
TI  - Balloon-Occluded Retrograde Transvenous Obliteration for the Treatment of Gastric
      Varices: Polidocanol Foam Versus Liquid Ethanolamine Oleate.
AB  - OBJECTIVE: The purpose of this study was to evaluate the clinical results of the
      management of gastric varices by balloon-occluded retrograde transvenous
      obliteration with polidocanol foam versus ethanolamine oleate. MATERIALS AND
      METHODS: Twenty patients treated with ethanolamine oleate and 21 patients treated
      with polidocanol foam were enrolled in this study. Early therapeutic effects were
      assessed mainly by dynamic contrast-enhanced CT. Subjective symptoms, objective
      findings associated with the procedures, and changes in laboratory data during
      the obliteration process were evaluated. Rebleeding from gastric varices was
      assessed after the procedures. RESULTS: Complete obliteration was confirmed in
      all but one case of early recanalization after treatment with polidocanol foam.
      One patient died of acute respiratory distress syndrome after treatment with
      ethanolamine oleate. The total sclerosant volume was significantly lower for 3%
      polidocanol foam (13.5 +/- 6.8 mL) than for 5% ethanolamine oleate (30.6 +/- 15.6
      mL) (p < 0.01). Polidocanol foam caused fewer severe reactions, including pain,
      during and after injection. High body temperature, hemoglobinuria, and reactive
      pleural effusion were not observed with polidocanol foam. The variance in
      laboratory data values associated with hemolysis was significantly greater with
      ethanolamine oleate. No postprocedural rebleeding from the gastric varices was
      observed during a median follow-up time of 39.5 months after procedures with
      ethanolamine oleate and 34 months after procedures with polidocanol foam.
      CONCLUSION: Polidocanol foam can achieve obliteration of gastric varices
      comparable to that of ethanolamine oleate but with a significantly lower
      sclerosant dose and reduced risk of hemolysis-induced complications and harmful
      reactions, including pain and fever.

PMID- 26295656
TI  - Internal Spermatic Vein Insufficiency in Varicoceles: A Different Entity in
      Adults and Adolescents?
AB  - OBJECTIVE: The purpose of this study was to determine whether phlebographic
      features can be used to discriminate adult from adolescent varicocele. MATERIALS
      AND METHODS: Left and right internal spermatic venograms of 191 adolescents (< 17
      years) and 224 adults (>= 25 years) were anonymized and evaluated. Phlebographic
      radioanatomic features (valves, duplications, collaterals, and classifications)
      were compared and analyzed with univariate tests. RESULTS: Insufficiency of the
      left internal spermatic vein (ISV) was confirmed in 409 of the 415 (99%)
      patients. Adults had no spontaneous opacification of the ISV during venography
      twice as frequently as adolescents (p = 0.001), a complex outflow into the renal
      vein 2.2 times as often (p = 0.021), and significantly more collaterals (p =
      0.030). Adolescents had a significantly lower number of competent valves and
      significantly more instances of nutcracker phenomenon (p = 0.001). According to
      the Bahren classification, the distribution of the types of ISVs was
      significantly different between adults and adolescents (p = 0.009). Insufficiency
      of the right ISV was encountered 2.4 times as frequently in adults as in
      adolescents (p < 0.001). In adults the maximum diameter of the ISV was
      significantly larger (p = 0.023). Bilateral ISV insufficiency was 2.2 times as
      frequent in adults (p < 0.001) as in adolescents. CONCLUSION: Left-sided
      varicoceles in adults are distinct from those in adolescents. In adults, reflux
      is likely to be induced via collateral pathways, whereas in adolescents
      congenital venous abnormalities are predominantly present. The higher prevalence
      and the greater diameter of a right insufficient ISV in adults, combined with the
      absence of venous anatomic differences, supports the hypothesis that right-sided
      varicocele is an evolutive disease.

PMID- 26295657
TI  - Breast Cancer Characteristics Associated With Digital Versus Film-Screen
      Mammography for Screen-Detected and Interval Cancers.
AB  - OBJECTIVE: The purpose of this study was to determine whether pathologic findings
      of screen-detected and interval cancers differ for digital versus film
      mammography. MATERIALS AND METHODS: Breast Cancer Surveillance Consortium data
      from 2003-2011 on 3,021,515 screening mammograms (40.3% digital, 59.7% film) of
      women 40-89 years old were reviewed. Cancers were considered screen detected if
      diagnosed within 12 months of an examination with positive findings and interval
      if diagnosed within 12 months of an examination with negative findings. Tumor
      characteristics for screen-detected and interval cancers were compared for
      digital versus film mammography by use of logistic regression models to estimate
      the odds ratio and 95% CI with adjustment for age, race and ethnicity, hormone
      therapy use, screening interval, examination year, and registry. Generalized
      estimating equations were used to account for correlation within facilities.
      RESULTS: Among 15,729 breast cancers, 85.3% were screen detected and 14.7% were
      interval. Digital and film mammography had similar rates of screen-detected (4.47
      vs 4.42 per 1000 examinations) and interval (0.73 vs 0.79 per 1000 examinations)
      cancers for digital versus film. In adjusted analyses, interval cancers diagnosed
      after digital examinations with negative findings were less likely to be American
      Joint Committee on Cancer stage IIB or higher (odds ratio, 0.69; 95% CI, 0.52
      0.93), have positive nodal status (odds ratio, 0.78; 95% CI, 0.64-0.95), or be
      estrogen receptor negative (odds ratio, 0.71; 95% CI, 0.56-0.91) than were
      interval cancers diagnosed after a film examination with negative findings.
      CONCLUSION: Screen-detected cancers diagnosed after digital and film mammography
      had similar rates of unfavorable tumor characteristics. Interval-detected cancers
      diagnosed after a digital examination were less likely to have unfavorable tumor
      features than those diagnosed after film mammography, but the absolute
      differences were small.

PMID- 26295659
TI  - Corrections.

PMID- 26295658
TI  - When Timing Is Everything: Are Placental MRI Examinations Performed Before 24
      Weeks' Gestational Age Reliable?
AB  - OBJECTIVE: The objective of our study was to determine if placental MRI
      examinations performed for the detection of abnormal placentation earlier than 24
      weeks' gestational age (GA) are more or less reliable than examinations performed
      at a later GA. MATERIALS AND METHODS: Two radiologists blinded to clinical,
      surgical, and pathologic reports retrospectively and independently reviewed 69
      placental MRI examinations for nine imaging signs associated with abnormal
      placentation. A consensus of the suspicion of abnormal placentation (including
      accreta, increta, or percreta) was determined using a 5-point (low to high
      suspicion) Likert scale and compared with pathologic or surgical findings or
      both. RESULTS: Seventeen placental MRI examinations were performed at GA 14-23
      weeks, and 52 placental MRI examinations were performed at GA 24-41 weeks.
      Reviewer agreement (Cronbach alpha) among the nine imaging signs was 0.86 (95%
      CI, 0.72-0.92) and 0.92 (95% CI, 0.92-0.94) for MRI examinations at GA 14-23
      weeks and GA 24-41 weeks, respectively. Pathologic or surgical evidence of
      abnormal placentation was found in 41% and 65% of the cases between GA 14-23
      weeks and GA 24-41 weeks, respectively. The AUC for the MRI-based consensus score
      and the presence of abnormal placentation for GA 14-23 weeks was 0.49 (95% CI,
      0.21-0.78) compared with 0.92 (95% CI, 0.83-1.0) for GA 24-41 weeks (p = 0.002).
      CONCLUSION: Placental MRI examinations performed before 24 weeks' GA unreliably
      predict abnormal placentation.

PMID- 26295660
TI  - Regarding Fat Suppression in MRI, When Are Spectral Techniques Preferred Over
      STIR, and Vice Versa?

PMID- 26295661
TI  - Quantitative Radiology Reporting in Oncology: Survey of Oncologists and
      Radiologists.
AB  - OBJECTIVE: Tumor quantification is essential for determining the clinical
      efficacy and response to established and evolving therapeutic agents in cancer
      trials. The purpose of this study was to seek the opinions of oncologists and
      radiologists about quantitative interactive and multimedia reporting. SUBJECTS
      AND METHODS: Questionnaires were distributed to 253 oncologists and registrars
      and to 35 radiologists at our institution through an online survey application.
      Questions were asked about current reporting methods, methods for Response
      Evaluation Criteria in Solid Tumors (RECIST) tumor measurement, and preferred
      reporting format. RESULTS: The overall response rates were 43.1% (109/253) for
      oncologists and 80.0% (28/35) for radiologists. The oncologists treated more than
      40 tumor types. Most of the oncologists (65.7% [67/102]) and many radiologists
      (44.4% [12/27]) (p = 0.020) deemed the current traditional qualitative radiology
      reports insufficient for reporting tumor burden and communicating measurements.
      Most of the radiologists (77.8% [21/27]) and oncologists (85.5% [71/83]) (p =
      0.95) agreed that key images with measurement annotations helped in finding
      previously measured tumors; however, only 43% of radiologists regularly saved key
      images. Both oncologists (64.2% [70/109]) and radiologists (67.9% [19/28]) (p =
      0.83) preferred the ability to hyperlink measurements from reports to images of
      lesions as opposed to text-only reports. Approximately 60% of oncologists
      indicated that they handwrote tumor measurements on RECIST forms, and 40% used
      various digital formats. Most of the oncologists (93%) indicated that managing
      tumor measurements within a PACS would be superior to handwritten data entry and
      retyping of data into a cancer database. CONCLUSION: Oncologists and radiologists
      agree that quantitative interactive reporting would be superior to traditional
      text-only qualitative reporting for assessing tumor burden in cancer trials. A
      PACS reporting system that enhances and promotes collaboration between
      radiologists and oncologists improves quantitative reporting of tumors.

PMID- 26295662
TI  - MRI and Ultrasound Imaging of the Shoulder Using Positional Maneuvers.
AB  - OBJECTIVE: The purpose of this article is to review the normal anatomy and
      pathologic conditions of the shoulder on the basis of the appearance on MR and
      ultrasound images obtained during performance of abduction external rotation and
      flexion adduction internal rotation positional maneuvers. CONCLUSION: Positional
      MRI and ultrasound are highly useful in evaluation of the shoulder. Knowledge of
      the normal appearance of anatomic structures and pathologic changes in
      nontraditional imaging planes is necessary to avoid pitfalls in interpretation.

PMID- 26295663
TI  - Acute Appendicitis: Use of Clinical and CT Findings for Modeling Hospital
      Resource Utilization.
AB  - OBJECTIVE: The purpose of this study was to retrospectively investigate
      associations between baseline CT findings in suspected acute appendicitis and
      subsequent hospital resource utilization. MATERIALS AND METHODS: One hundred
      thirty-eight patients (76 male and 62 female patients; mean [+/- SD] age, 40 +/-
      21 years) who were admitted for suspected acute appendicitis and underwent
      baseline CT were included. A single radiologist reviewed CT examinations for
      appendiceal-related findings. Linear and logistic regressions were performed to
      identify independent predictors of payer and hospital resource utilization.
      Combined performance of identified independent factors for predicting outcomes
      was determined. RESULTS: Greater age, lower Charlson comorbidity index (CCI),
      lesser appendiceal wall thickness, absence of loculated fluid collection, and
      absence of periappendiceal fluid were significant independent predictors of
      inpatient surgery (joint sensitivity, 92.7%; specificity, 65.8%). Smaller
      appendiceal diameter, absence of periappendiceal fluid, and laparoscopic surgery
      were significant independent predictors of same-day discharge (joint sensitivity,
      79.1%; specificity, 64.2%). Greater CCI, greater wall thickness, and presence of
      periappendiceal fluid were significant independent predictors of repeat
      abdominopelvic CT (joint sensitivity, 82.5%; specificity, 68.1%). Presence of an
      appendicolith was the only significant predictor of repeat emergency department
      visit within 30 days (sensitivity, 61.2%; specificity, 68.8%) and the only
      significant predictor of repeat inpatient admission within 30 days (sensitivity,
      63.6%; specificity, 68.5%). Greater appendiceal diameter and presence of free air
      were significant predictors of inpatient costs, and predicted costs were as
      follows: $8047 + ($745 * appendiceal diameter) if free air was absent; and $
      39,261 + ($4426 * appendiceal diameter) if free air was present. However, costs
      were poorly predicted when greater than $45,000. Sex, WBC count, and payer
      category were not independent predictors, relative to CT findings, of any
      outcome. CONCLUSION: Admission CT findings serve as independent predictors of
      hospital resource utilization in suspected acute appendicitis.

PMID- 26295664
TI  - Predicting Overall Survival in Patients With Metastatic Melanoma on
      Antiangiogenic Therapy and RECIST Stable Disease on Initial Posttherapy Images
      Using CT Texture Analysis.
AB  - OBJECTIVE: The purpose of this study was to use CT texture analysis to predict
      overall survival (OS) in patients with metastatic melanoma and stable disease
      (SD) according to the Response Evaluation Criteria in Solid Tumors (RECIST) on
      initial posttherapy CT images. MATERIALS AND METHODS: This retrospective study
      included 42 patients with metastatic melanoma who received bevacizumab therapy in
      the context of a randomized prospective phase II clinical trial. Target lesions
      on the baseline and initial posttherapy contrast-enhanced CT examinations were
      evaluated by CT texture analysis using TexRAD software before and after image
      filtering in patients with RECIST SD on initial posttherapy images. Cox
      proportional hazards models were used to assess the associations of CT texture
      analysis measurements and of other patient factors with OS. The AUC was used to
      evaluate predictive accuracy. RESULTS: In multivariate analysis (in 23 patients
      with RECIST SD; median OS, 1.51 years), absolute change in mean positive pixels
      at spatial scaling filter of 4 mm, change in tumor size, and baseline serum
      lactate dehydrogenase (LDH) level were predictors of OS (hazard ratio [HR] = 5.05
      for decrease in mean positive pixels at spatial scaling filter of 4 mm vs
      increase, p = 0.007; HR = 4.14 for > 5% increase in tumor size vs otherwise, p =
      0.025; and HR = 1.29 for every 100 IU/L increase in baseline LDH level, p =
      0.068). A prognostic index containing these three factors was highly accurate for
      predicting OS at 18 months (AUC = 0.917). CONCLUSION: In patients with metastatic
      melanoma and RECIST SD on initial post-therapy CT images, a model incorporating
      CT texture analysis of target lesions, tumor size changes, and baseline LDH
      levels was highly accurate in predicting OS.

PMID- 26295665
TI  - MDCT and MR Urogram Spectrum of Congenital Anomalies of the Kidney and Urinary
      Tract Diagnosed in Adulthood.
AB  - OBJECTIVE: Congenital anomalies of the kidneys and urinary tract (CAKUT)
      encompass a spectrum of anomalies that result from genetic, epigenetic,
      environmental, and molecular signal aberrations at key stages of urinary tract
      development. CAKUT can be seen incidentally on cross-sectional imaging of the
      abdomen or can be a cause for adult-onset chronic kidney disease, posing new
      challenges for nephrologists, urologists, and radiologists. CONCLUSION: Awareness
      of CAKUT and familiarity with their imaging findings permit optimal patient
      management and thorough workup to prevent hypertension and progression from CAKUT
      to renal failure. The purpose of this article is to review the cross-sectional
      imaging findings of CAKUT that may present in adulthood.

PMID- 26295666
TI  - Does Computer-Aided Diagnosis Permit Differentiation of Angiomyolipoma Without
      Visible Fat From Renal Cell Carcinoma on MDCT?
AB  - OBJECTIVE: The purpose of this study was to evaluate the diagnostic value of
      computer-aided diagnosis (CADx) in differentiating angiomyolipoma without visible
      fat from renal cell carcinoma (RCC) on MDCT. MATERIALS AND METHODS: The study
      included 406 patients who had 47 angiomyolipomas without visible fat and 359 RCCs
      smaller than 4 cm, all of which were diagnosed on the basis of findings from
      nephrectomy or percutaneous biopsy performed at our institution between 2000 and
      2011. MDCT (slice thickness, 2.5 mm for corticomedullary phase image or 5 mm for
      the other phase images) and clinical findings were blindly reviewed by two
      radiologists in a single session. At the time the study was performed,
      radiologist 1 had 8 years of experience, and radiologist 2 had 18 years of
      experience. On the basis of the MDCT and clinical findings, CADx classified renal
      tumors as angiomyolipoma and RCC, and each radiologist independently recorded the
      probability score (0-5) for angiomyolipoma. The accuracy of CADx versus
      radiologists in diagnosing angiomyolipoma was compared using ROC analysis.
      Interobserver agreement between the two radiologists was evaluated. RESULTS: CADx
      yielded an area under the curve (Az) value of 0.949, which was greater than the
      Az values yielded by radiologists 1 and 2 (0.872 and 0.782, respectively; p <
      0.05). In addition, the Az value for radiologist 1 was greater than that for
      radiologist 2 (p = 0.01). CADx with a threshold of -1.0085 showed greater
      sensitivity than radiologist 1 and greater sensitivity, specificity, and accuracy
      than radiologist 2 (p < 0.05). The interobserver agreement for the
      differentiation was fair (kappa = 0.289). CONCLUSION: CAD can improve diagnostic
      performance in differentiating angiomyolipoma from RCC. The diagnostic
      performance of radiologists is variable according to the clinical experience and
      physical and emotional states of the radiologists.

PMID- 26295668
TI  - CT Urography for Diagnosis of Upper Urinary Tract Urothelial Carcinoma: Are Both
      Nephrographic and Excretory Phases Necessary?
AB  - OBJECTIVE: The objective of our study was to compare the diagnostic performance
      of nephrographic phase only, excretory phase only, and both nephrographic and
      excretory phases of CT urography (CTU) for the detection of upper tract
      urothelial carcinoma. MATERIALS AND METHODS: Forty-nine consecutive patients with
      pathologically proven upper tract urothelial carcinoma who underwent a single
      bolus CTU examination were evaluated. Forty-nine control patients with normal
      findings on two CTU examinations performed at a 1-year interval were included.
      Two radiologists independently reviewed the 98 CTU examinations at three
      different sessions (nephrographic phase only, excretory phase only, and both
      nephrographic and excretory phases simultaneously) and rated the likelihood of
      the presence of a urothelial carcinoma in each segment of the renal collecting
      system and ureter using a 5-point scale. Sensitivity, specificity, and AUC of ROC
      curve were calculated per segment and per patient. RESULTS: A total of 314
      segments, 56 of which contained tumors, were evaluated. In the per-segment
      analysis for reviewers 1 and 2, the sensitivity, specificity, and AUC,
      respectively, were as follows: 88%, 98%, and 0.95 and 84%, 97%, and 0.94 for the
      nephrographic phase; 79%, 98%, and 0.91 and 89%, 98%, and 0.95 for the excretory
      phase; and 88%, 99%, and 0.95 and 89%, 99%, and 0.96 for the combined
      nephrographic and excretory phases. The AUC of the combined nephrographic and
      excretory phases was significantly higher than that of the nephrographic phase
      (per-patient analysis, reviewer 2) and that of excretory phase (per-segment
      analysis, reviewer 1) but was not significantly different in any other
      comparisons. CONCLUSION: The nephrographic and excretory phases are complementary
      for the detection of upper tract urothelial carcinoma.

PMID- 26295667
TI  - IV Administered Gadodiamide Enters the Lumen of the Prostatic Glands: X-Ray
      Fluorescence Microscopy Examination of a Mouse Model.
AB  - OBJECTIVE: Dynamic contrast-enhanced MRI (DCE-MRI) has become a standard
      component of multiparametric protocols for MRI examination of the prostate, and
      its use is incorporated into current guidelines for prostate MRI examination.
      Analysis of DCE-MRI data for the prostate is usually based on the distribution of
      gadolinium-based agents, such as gadodiamide, into two well-mixed compartments,
      and it assumes that gadodiamide does not enter into the glandular lumen. However,
      this assumption has not been directly tested. The purpose of this study was to
      use x-ray fluorescence microscopy (XFM) imaging in situ to measure the
      concentration of gadodiamide in the epithelia and lumens of the prostate of
      healthy mice after IV injection of the contrast agent. MATERIALS AND METHODS: Six
      C57Bl6 male mice (age, 28 weeks) were sacrificed 10 minutes after IV injection of
      gadodiamide (0.13 mmol/kg), and three mice were sacrificed after saline
      injection. Prostate tissue samples obtained from each mouse were harvested and
      frozen; 7-MUm-thick slices were sectioned for XFM imaging, and adjacent 5-MUm
      thick slices were sectioned for H and E staining. Elemental concentrations were
      determined from XFM images. RESULTS: A mean (+/- SD) baseline concentration of
      gadolinium of 0.01 +/- 0.01 mM was determined from XFM measurements of prostatic
      tissue samples when no gadodiamide was administered, and it was used to determine
      the measurement error. When gadodiamide was added, the mean concentrations of
      gadolinium in the epithelia and lumens in 32 prostatic glands from six mice were
      1.00 +/- 0.13 and 0.36 +/- 0.09 mM, respectively. CONCLUSION: Our data suggest
      that IV administration of gadodiamide results in uptake of contrast agent by the
      glandular lumens of the mouse prostate. We were able to quantitatively determine
      gadodiamide distributions in mouse prostatic epithelia and lumens.

PMID- 26295669
TI  - Prediction of Micrometastasis (< 1 cm) to Pelvic Lymph Nodes in Prostate Cancer:
      Role of Preoperative MRI.
AB  - OBJECTIVE: The purpose of this study was to retrospectively investigate whether
      preoperative MRI plays a key role in clinical prediction of micrometastasis (< 1
      cm) to pelvic lymph nodes in prostate cancer. MATERIALS AND METHODS: One hundred
      one patients with prostate cancer who underwent preoperative MRI and radical
      prostatectomy with pelvic lymph node dissection were included. None of the
      patients had a pelvic lymph node with a short-axis diameter of 1 cm or larger on
      MRI. Both clinical (prostate-specific antigen, biopsy Gleason score, greatest
      percentage of biopsy core, and percentage of positive cores) and MRI parameters
      (tumor apparent diffusion coefficient and tumor staging) were assessed. The
      univariate, multivariate, and ROC curve analyses were conducted. RESULTS: Of 101
      patients, nine (8.9%) had pelvic lymph node metastases. In univariate analysis,
      all of the clinical and MRI parameters were related to micrometastasis to pelvic
      lymph nodes (p < 0.05). However, multivariate analysis revealed that only
      preoperative MRI stage was significant (p = 0.044). AUC of preoperative MRI stage
      was 0.954 (odds ratio, 21.7). Respective sensitivity and specificity of
      preoperative tumor staging by MRI were 100% and 65.2% with cutoff of T3a or more,
      and 88.9% and 94.6% with cutoff of T3b for predicting micrometastasis to pelvic
      lymph nodes. CONCLUSION: Preoperative MRI staging may play a role in prediction
      of micrometastasis (< 1 cm) to pelvic lymph nodes in prostate cancer.

PMID- 26295670
TI  - Differentiation of Renal Tumor Histotypes: Usefulness of Quantitative Analysis of
      Contrast-Enhanced Ultrasound.
AB  - OBJECTIVE: The purpose of this study is to evaluate quantitative analysis of
      contrast-enhanced ultrasound (CEUS) in the differential diagnosis of renal tumor
      histotypes. MATERIALS AND METHODS: Between January 2010 and December 2013, 106
      clear cell renal cell carcinomas (RCCs) (mean [+/- SD] diameter, 3.7 +/- 1.8 cm),
      34 angiomyolipomas (mean diameter, 4.1 +/- 1.4 cm), 25 papillary RCCs (mean
      diameter, 3.5 +/- 1.1 cm), and 28 chromophobe RCCs (mean diameter, 2.9 +/- 0.9
      cm) underwent CEUS quantitative analysis. The dynamic vascular pattern was
      analyzed with the Fisher exact chi-square test, and rise time, time to peak
      (TTP), and tumor-to-cortex enhancement ratio were analyzed with the independent
      sample t test. RESULTS: Dynamic vascular pattern types I and III
      (hyperenhancement) were more common among clear cell RCCs, whereas type II
      (hypoenhancement) was more common among angiomyolipomas, papillary RCCs, and
      chromophobe RCCs. Irrespective of dynamic vascular pattern class, the rise time
      and TTP were the shortest in clear cell RCCs and were equal in angiomyolipomas,
      papillary, and chromophobe RCCs. The tumor-to-cortex enhancement ratio was the
      highest in clear cell RCCs, was second highest in angiomyolipomas, and was lowest
      but equal in papillary and chromophobe RCCs. Clear cell RCCs and angiomyolipomas
      accounted for the majority of the hyperenhancing group. The tumor-to-cortex
      enhancement ratio of clear cell RCCs was higher than that of angiomyolipomas.
      With tumor-to-cortex enhancement ratio greater than 146.0% as the cutoff to
      differentiate clear cell RCC from angiomyolipoma in the hyperenhanced group, the
      sensitivity and specificity were each 71.4%. In the hypoenhanced group, the tumor
      to-cortex enhancement ratio was the same in clear cell RCCs and angiomyolipomas
      but was higher in papillary and chromophobe RCCs. With tumor-to-cortex
      enhancement ratio greater than 54.2% as the cutoff point to differentiate clear
      cell RCCs from papillary and chromophobe RCCs, the sensitivity and specificity
      were 95.5% and 94.8%, respectively, whereas with a tumor-to-cortex enhancement
      ratio greater than 57.4% as the cutoff point to differentiate angiomyolipomas
      from papillary and chromophobe RCCs, the sensitivity and specificity were 90.0%
      and 96.4%, respectively. CONCLUSION: Quantitative analysis of CEUS can show
      quantification of enhancement features of different renal tumor histotypes and
      may be helpful in their differential diagnosis.

PMID- 26295671
TI  - Application of Texture Analysis in the Differential Diagnosis of Benign and
      Malignant Thyroid Nodules: Comparison With Gray-Scale Ultrasound and
      Elastography.
AB  - OBJECTIVE: The purposes of this study were to investigate the optimal subset for
      texture analysis by use of a histogram and cooccurrence matrix in the
      differential diagnosis of benign and malignant thyroid nodules and to compare the
      results with those of gray-scale ultrasound and elastography. MATERIALS AND
      METHODS: From a retrospective search of an institutional database between June
      and November 2009, 633 solid nodules 5 mm or larger from 613 patients who
      underwent gray-scale ultrasound and elastography and subsequent ultrasound-guided
      fine-needle aspiration were included in this study. Each nodule was categorized
      as probably benign or suspicious of being malignant according to findings at gray
      scale ultrasound and elastography. Histogram parameters (mean, SD, skewness,
      kurtosis, and entropy) and cooccurrence matrix parameters (contrast, correlation,
      uniformity, homogeneity, and entropy) were extracted from gray-scale ultrasound
      and elastographic images. The diagnostic performances of gray-scale ultrasound,
      elastography, and texture analysis for differentiating thyroid nodules were
      evaluated. RESULTS: Gray-scale ultrasound had the best diagnostic performance
      with an ROC AUC (Az) of 0.809 among all parameters. Elastography had
      significantly poorer performance (Az = 0.646) than gray-scale ultrasound (p <
      0.001). Mean extracted from gray-scale ultrasound had the highest Az (0.675)
      among all histogram and cooccurrence matrix parameters extracted from gray-scale
      ultrasound and elastographic images. However, mean and the combination of mean
      and gray-scale ultrasound had poorer performance than gray-scale ultrasound
      alone. CONCLUSION: Using texture analysis does not improve diagnostic performance
      in the evaluation of thyroid cancers.

PMID- 26295672
TI  - Metal Artifact Reduction: Added Value of Rapid-Kilovoltage-Switching Dual-Energy
      CT in Relation to Single-Energy CT in a Piglet Animal Model.
AB  - OBJECTIVE: The purpose of this article is to evaluate virtual monochromatic
      spectral imaging and metal artifact reduction software for reducing metal
      artifact and to compare it with conventional single-energy CT (SECT) in an animal
      model. MATERIALS AND METHODS: Postmortem juvenile (n = 5) and adult (n = 1) swine
      specimens were scanned with SECT followed by a dual-energy CT (DECT) pediatric
      protocol after the insertion of two rods into their paraspinal thoracolumbar
      regions. Virtual monochromatic spectral images were extrapolated from DECT images
      at five monoenergetic levels (64, 69, 75, 88, and 105 keV) with and without the
      use of metal artifact reduction software. Images were evaluated by a 5-point
      scoring system for the extent of metallic artifacts and image interpretability in
      soft-tissue and bone windows. The density in the most pronounced artifact was
      measured. CT dose index was recorded. RESULTS: In studies without metal artifact
      reduction software, higher energy reconstructions resulted in fewer artifacts and
      better image interpretability in both soft-tissue and bone windows (p < 0.0001).
      Artifact density decreased from -792 HU at 64 keV to -128 HU at 105 keV without
      the use of metal artifact reduction software. No difference was noted in
      attributes' scores or in artifact density in studies using metal artifact
      reduction software (p > 0.05). DECT studies showed lower scores compared with
      SECT with regard to all attributes. A new faint perimetallic hypodense halo was
      seen in all studies with metal artifact reduction software. The CT dose index of
      DECT was 1.18-3.56 times higher than that of SECT techniques. CONCLUSION: DECT at
      all energy levels with metal artifact reduction software and higher energy
      extrapolations without metal artifact reduction software reduced metallic
      artifact and enhanced image interpretability compared with SECT. Radiation dose
      with DECT could be significantly higher than SECT.

PMID- 26295673
TI  - Incidental Thyroid Nodules Detected on Thoracic Contrast-Enhanced CT in the
      Pediatric Population: Prevalence and Outcomes.
AB  - OBJECTIVE: The purpose of this study was to investigate the prevalence and
      outcomes of incidental thyroid nodules detected on thoracic contrast-enhanced CT
      (CECT) in the pediatric population. MATERIALS AND METHODS: We used our hospital
      information system to retrospectively identify all consecutive pediatric patients
      (< 21 years old) with newly detected thyroid nodules reported on thoracic CECT
      performed between January 2006 and January 2013. The study population was
      categorized into two groups: patients with (group 1) and without (group 2) an
      available follow-up thyroid ultrasound study. Two pediatric radiologists
      systematically reviewed the CT studies, available follow-up thyroid ultrasound
      studies, and outcomes of patients meeting the inclusion criteria. For patients
      without an available follow-up ultrasound study (group 2), the duration of
      clinical follow-up was also evaluated. If a biopsy was performed, the pathologic
      diagnosis was correlated with the imaging findings. RESULTS: The study population
      consisted of 35 thoracic CECT studies from 35 pediatric patients (18 females, 17
      males; mean age, 13 +/- 6.2 [SD] years) who met the inclusion criteria. The
      prevalence of incidental thyroid nodules detected on thoracic CECT in our study
      population was 1.4% (35/2525 patients; 95% CI, 1-2%). Seventeen of the 35 (49%)
      patients (group 1) underwent follow-up thyroid ultrasound, six (17%) of whom
      ultimately underwent biopsy of the thyroid nodule for pathologic diagnosis. Among
      these six patients, two (33%) were found to have malignant thyroid nodules:
      papillary thyroid carcinoma and thyroid involvement by an underlying Burkitt
      lymphoma. Therefore, the prevalence of malignancy among incidentally detected
      thyroid nodules on thoracic CECT in pediatric patients in this study was 5.7%
      (2/35 patients; 95% CI, 2-18%). The remaining four of six patients (67%) had
      benign thyroid nodules. Eighteen of the 35 (51%) patients (group 2) had only
      clinical follow-up information (mean follow-up, 27.1 +/- 21.1 months); no
      neoplasm subsequently developed from incidentally detected thyroid nodules among
      this subset. CONCLUSION: Thyroid nodules detected incidentally on thoracic CECT
      are rare in pediatric patients. However, when thyroid nodules are present,
      ultrasound (with or without biopsy for pathologic evaluation) is an appropriate
      strategy because of the rare but real possibility of an underlying thyroid
      malignancy in the pediatric population.

PMID- 26295674
TI  - Direct-Conversion Molecular Breast Imaging of Invasive Breast Cancer: Imaging
      Features, Extent of Invasive Disease, and Comparison Between Invasive Ductal and
      Lobular Histology.
AB  - OBJECTIVE: The purposes of this study were to compare the tumor appearance of
      invasive breast cancer on direct-conversion molecular breast imaging using a
      standardized lexicon and to determine how often direct-conversion molecular
      breast imaging identifies all known invasive tumor foci in the breast, and
      whether this differs for invasive ductal versus lobular histologic profiles.
      MATERIALS AND METHODS: Patients with prior invasive breast cancer and concurrent
      direct-conversion molecular breast imaging examinations were retrospectively
      reviewed. Blinded review of direct-conversion molecular breast imaging
      examinations was performed by one of two radiologists, according to a validated
      lexicon. Direct-conversion molecular breast imaging findings were matched with
      lesions described on the pathology report to exclude benign reasons for direct
      conversion molecular breast imaging findings and to document direct-conversion
      molecular breast imaging-occult tumor foci. Associations between direct
      conversion molecular breast imaging findings and tumor histologic profiles were
      examined using chi-square tests. RESULTS: In 286 patients, 390 invasive tumor
      foci were present in 294 breasts. A corresponding direct-conversion molecular
      breast imaging finding was present for 341 of 390 (87%) tumor foci described on
      the pathology report. Invasive ductal carcinoma (IDC) tumor foci were more likely
      to be a mass (40% IDC vs 15% invasive lobular carcinoma [ILC]; p < 0.001) and to
      have marked intensity than were ILC foci (63% IDC vs 32% ILC; p < 0.001). Direct
      conversion molecular breast imaging correctly revealed all pathology-proven foci
      of invasive disease in 79.8% of cases and was more likely to do so for IDC than
      for ILC (86.1% vs 56.7%; p < 0.0001). Overall, direct-conversion molecular breast
      imaging showed all known invasive foci in 249 of 286 (87%) patients. CONCLUSION:
      Direct-conversion molecular breast imaging features of invasive cancer, including
      lesion type and intensity, differ by histologic subtype. Direct-conversion
      molecular breast imaging is less likely to show all foci of ILC compared with
      IDC.

PMID- 26295675
TI  - Medicolegal--Malpractice and Ethical Issues in Radiology. Reporting Agreement or
      Disagreement When Overreading Outside Radiology Examinations.

PMID- 26295676
TI  - Commonly Overlooked DWI Parameters in the Abdomen and Pelvis.

PMID- 26295677
TI  - Imaging of Perihilar Cholangiocarcinoma.

PMID- 26295678
TI  - Reply to "Imaging of Perihilar Cholangiocarcinoma".

PMID- 26295679
TI  - Intravascular Lymphoma.

PMID- 26295681
TI  - Erratum.

PMID- 26295680
TI  - Reply to "Intravascular Lymphoma".

PMID- 26295684
TI  - Investigating age-related changes in anterior and posterior neural activity
      throughout the information processing stream.
AB  - Event-related potential (ERP) and other functional imaging studies often
      demonstrate age-related increases in anterior neural activity and decreases in
      posterior activity while subjects carry out task demands. It remains unclear
      whether this "anterior shift" is limited to late cognitive operations like those
      indexed by the P3 component, or is evident during other stages of information
      processing. The temporal resolution of ERPs provided an opportunity to address
      this issue. Temporospatial principal component analysis (PCA) was used to
      identify underlying components that may be obscured by overlapping ERP waveforms.
      ERPs were measured during a visual oddball task in 26 young, 26 middle-aged, and
      29 old subjects who were well-matched for IQ, executive function, education, and
      task performance. PCA identified six anterior factors peaking between ~140 ms and
      810 ms, and four posterior factors peaking between ~300 ms and 810 ms. There was
      an age-related increase in the amplitude of anterior factors between ~200 and 500
      ms, and an age-associated decrease in amplitude of posterior factors after ~500
      ms. The increase in anterior processing began as early as middle-age, was
      sustained throughout old age, and appeared to be linear in nature. These results
      suggest that age-associated increases in anterior activity occur after early
      sensory processing has taken place, and are most prominent during a period in
      which attention is being marshaled to evaluate a stimulus. In contrast, age
      related decreases in posterior activity manifest during operations involved in
      stimulus categorization, post-decision monitoring, and preparation for an
      upcoming event.

PMID- 26295686
TI  - Preparation of geopolymer-based inorganic membrane for removing Ni(2+) from
      wastewater.
AB  - A type of novel free-sintering and self-supporting inorganic membrane for
      wastewater treatment was fabricated in this study. This inorganic membrane was
      synthesised using metakaolin and sodium silicate solutions moulded according to a
      designed molar ratio (SiO2/Al2O3=2.96, Na2O/Al2O3=0.8 and H2O/Na2O=19) which
      formed a homogenous structure and had a relative concentration pore size
      distribution, via scanning electron microscopy (SEM) and Brunauer-Emmett-Teller
      (BET) analyses. In this work, the Ni(2+) removal effect of geopolymer inorganic
      membrane was studied under different pH value, initial concentration of Ni(2+)
      solutions and initial operation temperature. Results showed that geopolymer
      inorganic membrane efficiently removes Ni(2+) from wastewater because of the
      combined actions of the adsorption and rejection of this membrane on Ni(2+)
      during membrane separation. Therefore, geopolymer inorganic membrane may have
      positive potential applications in removing Ni(2+) or other heavy metal ions from
      aqueous industrial wastewater. 

PMID- 26295685
TI  - Band structure of graphene modulated by Ti or N dopants and applications in gas
      sensoring.
AB  - The exploration of novel sensors for NO2 detection is particularly important in
      material and environmental sciences. In this work, the HOMO-LUMO gap of graphene,
      Ti- or N-doped graphene is investigated by DFT methods. The adsorption of NO2,
      NO, and O2 on Ti- or N-doped graphene of different sizes is also explored.
      Results reveal that the interactions between gases (NO2, NO, and O2) and Ti- or N
      doped graphenes is not affected by the size of graphene. The doped Ti greatly
      improves the interactions between gases and graphene whereas the doped N has no
      effect on those interactions. The HOMO- LUMO gap of Ti-doped graphene can be
      modulated by adsorption of the gases. The cross effect of the NO and O2 is also
      investigated, and it is demonstrated that Ti-doped graphene has specific
      interactions with NO2. Thus, Ti-doped graphene can be a candidate for NO2 sensor
      materials. Furthermore, doping the graphene with Ti or N improves the sensitivity
      of the sheets toward NO2, which can be trapped and detected by the intrinsic
      graphene. Efficient sensors are rationally designed to diversify their
      applications in environmental science and engineering. 

PMID- 26295687
TI  - Differences in the pathological diagnosis of colorectal neoplasia between the
      East and the West: Present status and future perspectives from Japan.
AB  - It is well known that there are discrepancies in the diagnosis of
      gastrointestinal neoplasia between Western and Japanese pathologists. In the
      West, colorectal cancer (CRC) is defined by invasion through the muscularis
      mucosa into the submucosa, especially depending on the presence of desmoplasia.
      In Japan, however, CRC is defined based on a combination of nuclear and
      architectural abnormalities, regardless of invasion status. As a result,
      intramucosal carcinoma is diagnosed as high-grade dysplasia and even intramucosal
      carcinoma with poorly differentiated component is classified as 'Tis' in the
      West. It is logical and reasonable that the term 'T1' is used to currently
      describe intramucosal carcinoma. Use of the term 'high-grade dysplasia' for
      intramucosal CRC is outdated. In order to determine appropriate clinical
      treatment of CRC, the various risk factors of metastasis should be fully
      evaluated. With improved contributions and communication between pathologists and
      clinicians, overtreatment and inadequate follow up can be avoided. The
      discrepancies in the diagnosis of CRC between Western and Japanese pathologists
      may be addressed by an increase in East-West exchange. In addition, in the
      future, molecular analysis may also be useful for establishment of standardized
      diagnostic criteria of CRC. 

PMID- 26295688
TI  - Fluoride-induced oxidative stress is involved in the morphological damage and
      dysfunction of liver in female mice.
AB  - Fluoride (F), one of the most toxic environmental and industrial pollutants, is
      known to exert hepatotoxicity. The contribution of oxidative stress to the F
      tolerance of liver remains largely unknown. In this study, the morphological and
      ultrastructural characteristics of liver were observed using hematoxylin and
      eosin staining and transmission electron microscopy (TEM), respectively.
      Oxidative-stress participations was analysed and the mRNA expression levels of
      catalase (Cat), glutathione peroxidase 1 (GSH-Px1), nitric oxide synthase 2
      (NOS2), and superoxide dismutase 1 (SOD1) were investigated by real-time PCR.
      Changes in liver-function parameters were also detected. Results showed that the
      reactive content of reactive oxygen species increased significantly, whereas SOD
      and GSH-Px activities, as well as total anti-oxidising capability (T-AOC),
      decreased significantly, with increased nitric oxide (NO) and malondialdehyde
      (MDA) contents in liver and serum after 70days of F treatment. The mRNA
      expression levels of Cat, GSH-Px1, and SOD were significantly downregulated,
      whereas NOS2 mRNA expression level was up upregulated, after F treatment for
      70days. Light microscopy also revealed that hepatocytes were fused into pieces;
      cell boundaries were unclear, and nuclei were lightly stained. TEM further showed
      that hepatocytes were characterised by vague nuclear and mitochondrial membranes,
      dilated endoplasmic reticulum, and aggravated vacuolar degeneration. Activities
      of alanine transaminase, aspartate aminotransferase, alkaline phosphatase and
      lactate dehydrogenase, as well as the level of total bilirubin in serum
      increased. Overall, these results indicated that F interfered with the balance of
      antioxidase activity and morphological changes in liver, which were involved in
      mouse liver dysfunction.

PMID- 26295689
TI  - Evaluation of the genotoxic potential of soil contaminated with mineral coal
      tailings on snail Helix aspersa.
AB  - Coal remains an important source of energy, although the fuel is a greater
      environmental pollutant. Coal is a mixture of several chemicals, especially
      inorganic elements and polycyclic aromatic hydrocarbons (PAH). Many of these
      compounds have mutagenic and carcinogenic effects on organisms exposed to this
      mineral. In the town of Charqueadas (Brazil), the tailings from mining were used
      for landfill in the lower areas of the town, and the consequence is the formation
      of large deposits of this material. The purpose of this study was to evaluate the
      genotoxic potential of soil samples contaminated by coal waste in different sites
      at Charqueadas, using the land snail Helix aspersa as a biomonitor organism.
      Thirty terrestrial snails were exposed to different treatments: 20 were exposed
      to the soil from two different sites in Charqueadas (site 1 and 2; 10 in each
      group) and 10 non-exposed (control group). Hemolymph cells were collected after
      24h, 5days and 7days of exposure and comet assay, micronucleus test, oxidative
      stress tests were performed. Furthermore, this study quantified the inorganic
      elements present in soil samples by the PIXE technique and polycyclic aromatic
      hydrocarbons (PAH) by HPLC. This evaluation shows that, in general, soils from
      sites in Charqueadas, demonstrated a genotoxic effect associated with increased
      oxidative stress, inorganic and PAH content. These results demonstrate that the
      coal pyrite tailings from Charqueadas are potentially genotoxic and that H.
      aspersa is confirmed to be a sensitive instrument for risk assessment of
      environmental pollution.

PMID- 26295690
TI  - A Novel ACE Inhibitory Peptide Ala-His-Leu-Leu Lowering Blood Pressure in
      Spontaneously Hypertensive Rats.
AB  - Ala-His-Leu-Leu (AHLL) was isolated and purified from the loach (Misgurnus
      anguillicaudatus) hydrolysate in our previous study. The aim of this study was to
      investigate the antihypertensive effects of angiotensin-I-converting enzyme (ACE)
      inhibitory peptide AHLL in spontaneously hypertensive rats (SHRs). AHLL showed
      good antihypertensive effects in SHRs during the long-term oral administration
      and no allergic reactions or coughing were observed. After 2 months of oral
      administration of AHLL, the body weight growth was normal. The decrements in
      systolic blood pressure of the high dose (5 mg/kg bw) and the low dose of AHLL (1
      mg/kg bw) treatment groups were 22.1 and 5.0 mmHg at week 8, respectively.
      Compared to the control group, the concentrations of triglyceride and sodium in
      serum were reduced significantly in the high-dose group after 2 months. The ACE
      activity of kidney and lung decreased significantly, which indicated that AHLL
      exerted an antihypertensive effect on kidney and lung and they were the target
      sites of AHLL. These results strongly supported the in vivo antihypertensive
      mechanism of AHLL. 

PMID- 26295691
TI  - The antibacterial activity and toxicity of enrofloxacin are decreased by
      nanocellulose conjugated with aminobenzyl purin.
AB  - The first aim of this study was to synthesize nanocellulose conjugated with
      aminobenzyl purin (NCABP), and the second aim was to evaluate the effect of NCABP
      on both toxicity and antibacterial activity of enrofloxacin. Here, the adsorption
      of enrofloxacin by NCABP was first modeled by molecular dynamic (MD) simulation.
      In the next step, NCABP was synthesized, and was exposed to enrofloxacin, 1000
      MUg mL(-1), at various conditions. Then, the quantity of adsorption and release
      was separately measured. Furthermore, both toxicity and antibacterial activity of
      NCABP, enrofloxacin, and (NCABP+enrofloxacin) were separately evaluated. In this
      study, MD simulation clearly showed the adsorption after 50 picoseconds. The
      adsorption tests revealed that the increase of incubation time and NCABP
      concentration, at range of 50-200 MUg mL(-1), led to increase of adsorption.
      Moreover, the decrease of pH led to increase of adsorption. Interestingly, NCABP
      could adsorb enrofloxacin, up to 1000 MUg mL(-1), in different types of meat.
      Moreover, the increase of incubation time and temperature did not release
      enrofloxacin, but the increase of pH increased release. This study showed that
      both toxicity and antibacterial activity of enrofloxacin were decreased when
      exposed together with NCABP.

PMID- 26295692
TI  - Do changes in spring phenology affect earlywood vessels? Perspective from the
      xylogenesis monitoring of two sympatric ring-porous oaks.
AB  - This study addresses relationships between leaf phenology, xylogenesis, and
      functional xylem anatomy in two ring-porous oak species, the temperate Quercus
      robur and the sub-Mediterranean Q. pyrenaica. Earlywood vessel (EV) formation and
      leaf phenology were monitored in 2012 and 2013. Ten individuals per species were
      sampled at each of three sites located in NW Iberian Peninsula. EV areas measured
      on microcore sections were used to calculate the hydraulic tree diameter (Dh ),
      in order to model relationships to phenology. Thermal requirements were evaluated
      using growing degree days (GDD). A species-specific timing of growth resumption
      was found. The onset of EV formation and budburst were associated to a particular
      GDD in each species. The onset and duration of EV enlargement affected Dh (and EV
      size) in Q. robur, but hardly in Q. pyrenaica. The relationship between the
      timings of EV formation and xylem structure appears to be stronger for the
      temperate oak, whose larger vessels may result from thermal-induced earlier
      resumption. In contrast, the sub-Mediterranean oak would maintain a more
      conservative hydraulic architecture under warming conditions. 

PMID- 26295693
TI  - The cross-cut statistic and its sensitivity to bias in observational studies with
      ordered doses of treatment.
AB  - A common practice with ordered doses of treatment and ordered responses, perhaps
      recorded in a contingency table with ordered rows and columns, is to cut or
      remove a cross from the table, leaving the outer corners--that is, the high
      versus-low dose, high-versus-low response corners--and from these corners to
      compute a risk or odds ratio. This little remarked but common practice seems to
      be motivated by the oldest and most familiar method of sensitivity analysis in
      observational studies, proposed by Cornfield et al. (1959), which says that to
      explain a population risk ratio purely as bias from an unobserved binary
      covariate, the prevalence ratio of the covariate must exceed the risk ratio.
      Quite often, the largest risk ratio, hence the one least sensitive to bias by
      this standard, is derived from the corners of the ordered table with the central
      cross removed. Obviously, the corners use only a portion of the data, so a focus
      on the corners has consequences for the standard error as well as for bias, but
      sampling variability was not a consideration in this early and familiar form of
      sensitivity analysis, where point estimates replaced population parameters. Here,
      this cross-cut analysis is examined with the aid of design sensitivity and the
      power of a sensitivity analysis.

PMID- 26295694
TI  - Implementing the Use of Chemical-Free Products in a Perinatal Unit.
AB  - OBJECTIVE: To develop a process to identify, adopt, and increase individual
      awareness of the use of chemical-free products in perinatal hospital units and to
      develop leadership skills of the fellow/mentor pair through the Sigma Theta Tau
      International Maternal-Child Health Nurse Leadership Academy (STTI MCHNLA).
      DESIGN: Pretest/posttest quality improvement project. SETTING: Tertiary care 80
      bed perinatal unit. PATIENTS: Mothers and newborns on perinatal unit.
      INTERVENTIONS/MEASUREMENTS: The chemical hazard ratings of products currently in
      use and new products were examined and compared. Chemical-free products were
      selected and introduced to the hospital system, and education programs were
      provided for staff and patients. We implemented leadership tools taught at the
      STTI MCHNLA to facilitate project success. Pre- and postproject evaluations were
      used to determine interest in the use of chemical-free products and satisfaction
      with use of the new products. Cost savings were measured. RESULTS: Products
      currently in use contained potentially harmful chemicals. New, chemical-free
      products were identified and adopted into practice. Participants were interested
      in using chemical-free products. Once new products were available, 71% of
      participants were positive about using them. The fellow and mentor experienced
      valuable leadership growth throughout the project. CONCLUSIONS: The change to
      chemical-free products has positioned the organization and partner hospitals as
      community leaders that set a health standard to reduce environmental exposure for
      patients, families, and staff. The fellow and mentor learned new skills to assist
      in practice changes in a large organization by using the tools shared in the STTI
      MCHNLA.

PMID- 26295695
TI  - Separation of active laccases from Pleurotus sapidus culture supernatant using
      aqueous two-phase systems in centrifugal partition chromatography.
AB  - For the production of bio active compounds, e.g., active enzymes or antibodies, a
      conserved purification process with a minimum loss of active compounds is
      necessary. In centrifugal partition chromatography (CPC), the separation effect
      is based on the different distribution of the components to be separated between
      two immiscible liquid phases. Thereby, one liquid phase is kept stationary in
      chambers by a centrifugal field and the mobile phase is pumped through via
      connecting ducts. Aqueous two phase systems (ATPS) are known to provide benign
      conditions for biochemical products and seem to be promising when used in CPC for
      purification tasks. However, it is not known if active biochemical compounds can
      "survive" the conditions in a CPC where strong shear forces can occur due to the
      two-phasic flow under centrifugal forces. Therefore, this aspect has been faced
      within this study by the separation of active laccases from a fermentation broth
      of Pleurotus sapidus. After selecting a suitable ATPS and operating conditions,
      the activity yield was calculated and the preservation of the active enzymes
      could be observed. Therefore, CPC could be shown as potentially suitable for the
      purification of bio-active compounds. 

PMID- 26295696
TI  - Permeation profiles of resveratrol cream delivered through porcine vaginal
      mucosa: Evaluation of different HPLC stationary phases.
AB  - Trans-resveratrol affects biological systems in a multitude of ways, but its oral
      bioavailability is remarkably poor due to in vivo metabolization. This drawback
      has fomented the development of new strategies for systemic delivery, such as
      transmucosal delivery via the vaginal route, which is our main focus here. In
      this sense, our pioneering study purposed to evaluate the trans-resveratrol
      permeation efficacy through this route. For that, we used a previously validated
      method and tested it with three different stationary phases: a commercial C18
      column and two laboratory-made chromatographic columns containing
      poly(methyloctadecylsiloxane) (PMODS) thermally immobilized onto zirconized
      silica (Zr-PMODS) or titanized silica (Ti-PMODS). The permeation experiments
      showed that resveratrol, in the formulation used, was not successfully delivered
      to the bloodstream - it was actually retained within the vaginal mucosa, which
      suggests a local use rather a systemic one. 

PMID- 26295698
TI  - Preferred reporting items for studies mapping onto preference-based outcome
      measures: The MAPS statement.
AB  - 'Mapping' onto generic preference-based outcome measures is increasingly being
      used as a means of generating health utilities for use within health economic
      evaluations. Despite publication of technical guides for the conduct of mapping
      research, guidance for the reporting of mapping studies is currently lacking. The
      MAPS (MApping onto Preference-based measures reporting Standards) statement is a
      new checklist, which aims to promote complete and transparent reporting of
      mapping studies. The primary audiences for the MAPS statement are researchers
      reporting mapping studies, the funders of the research, and peer reviewers and
      editors involved in assessing mapping studies for publication. A de novo list of
      29 candidate reporting items and accompanying explanations was created by a
      working group comprised of six health economists and one Delphi methodologist.
      Following a two-round, modified Delphi survey with representatives from academia,
      consultancy, health technology assessment agencies and the biomedical journal
      editorial community, a final set of 23 items deemed essential for transparent
      reporting, and accompanying explanations, was developed. The items are contained
      in a user friendly 23 item checklist. They are presented numerically and
      categorised within six sections, namely: (i) title and abstract; (ii)
      introduction; (iii) methods; (iv) results; (v) discussion; and (vi) other. The
      MAPS statement is best applied in conjunction with the accompanying MAPS
      explanation and elaboration document. It is anticipated that the MAPS statement
      will improve the clarity, transparency and completeness of reporting of mapping
      studies. To facilitate dissemination and uptake, the MAPS statement is being co
      published by seven health economics and quality of life journals, and broader
      endorsement is encouraged. The MAPS working group plans to assess the need for an
      update of the reporting checklist in five years' time. 

PMID- 26295699
TI  - Quantifying Asymmetry and Scar Quality of Children With Repaired Cleft Lip and
      Palate Using Symnose 2.
AB  - The Symnose semiautomated assessment of outcome of the appearance of the repaired
      cleft lip and nose was developed to measure asymmetry. Symnose 2 has been further
      developed to include quantification of the extent of scar color, intensity, and
      contour and midline dehiscence, underexpressed in the measurement of asymmetry.

PMID- 26295697
TI  - Development and validation of an UPLC-MS/MS method for the quantification of
      columbin in biological matrices: Applications to absorption, metabolism, and
      pharmacokinetic studies.
AB  - The aim of this study is to develop a sensitive UPLC-MS/MS method to quantify
      columbin in biological sample. Chromatographic separation was accomplished using
      Waters UPLC BEH C18 column with acetonitrile and 0.1% of formic acid in water as
      the mobile phases. The mass analysis was performed on an API 5500 Qtrap mass
      spectrometer via multiple reaction monitoring (MRM) with positive scan mood. The
      one-step protein precipitation by methanol was used to extract the analyte from
      blood samples. The results showed that the linear response range for columbin was
      1.22-2,500nM. The intra and inter day variances were less than 15% and the
      accuracy was in acceptable range (85-115%). The analysis was done within 3.0min,
      and only 50MUL of blood was needed. The validated method was used to determine
      the pharmacokinetic profile of columbin in Wistar rats, and its transport
      characteristics in the Caco-2 cell culture model. The results showed that
      columbin was poorly bioavailable (2.8% p.o. and 14% i.p.) in rats, but its
      transport was rapid across the Caco-2 cell monolayers, suggesting that extensive
      first-pass metabolism in the liver was the likely reason for its poor
      bioavailability. The results revealed that the validated method can be used for
      columbin analysis in both bioequivalent buffer and blood. 

PMID- 26295700
TI  - Isolation of Tibet orbivirus, TIBOV, from Culicoides Collected in Yunnan, China.
AB  - We isolated a novel virus strain (YN12246) from Culicoides spp. specimens
      collected at the China-Laos-Myanmar border in southern Yunnan Province. This
      virus had a cytopathic effect (CPE) on both insect cells (C6/36) and mammalian
      cells (BHK-21). Electron microscopy revealed the structure of the virions to be
      spherical with a diameter of 75 nm. Polyacrylamide gel analysis demonstrated that
      the viral genome consisted of 10 segments of double-stranded RNA (dsRNA), with a
      distribution pattern of 3-3-3-1. The coding sequences of 9 genome segments of
      YN12246 (Seg1, Seg3-Seg10) were obtained by high-throughput sequencing and Sanger
      sequencing. Comparisons of conserved genome segments 1 and 3 (Seg1 and Seg3),
      encoding the polymerase-VP1 and sub-core T2 protein, respectively, showed that
      YN12246 groups with the Culicoides-borne orbiviruses. The highest levels of
      sequence identity were detected between YN12246 and Tibet orbivirus (TIBOV),
      indicating that they belong to the same virus species (with amino acid identity
      of 98.8% and 96.4% for the polymerase and T2 protein, respectively). The data
      presented here confirm that YN12246 is a member of the TIBOV species, which was
      first isolated from mosquitoes in 2009. This is the first report of the isolation
      of TIBOV from Culicoides. 

PMID- 26295701
TI  - Heparan Sulfate Biosynthesis Enzyme, Ext1, Contributes to Outflow Tract
      Development of Mouse Heart via Modulation of FGF Signaling.
AB  - Glycosaminoglycans are important regulators of multiple signaling pathways. As a
      major constituent of the heart extracellular matrix, glycosaminoglycans are
      implicated in cardiac morphogenesis through interactions with different signaling
      morphogens. Ext1 is a glycosyltransferase responsible for heparan sulfate
      synthesis. Here, we evaluate the function of Ext1 in heart development by
      analyzing Ext1 hypomorphic mutant and conditional knockout mice. Outflow tract
      alignment is sensitive to the dosage of Ext1. Deletion of Ext1 in the mesoderm
      induces a cardiac phenotype similar to that of a mutant with conditional deletion
      of UDP-glucose dehydrogenase, a key enzyme responsible for synthesis of all
      glycosaminoglycans. The outflow tract defect in conditional Ext1
      knockout(Ext1f/f:Mesp1Cre) mice is attributable to the reduced contribution of
      second heart field and neural crest cells. Ext1 deletion leads to downregulation
      of FGF signaling in the pharyngeal mesoderm. Exogenous FGF8 ameliorates the
      defects in the outflow tract and pharyngeal explants. In addition, Ext1
      expression in second heart field and neural crest cells is required for outflow
      tract remodeling. Our results collectively indicate that Ext1 is crucial for
      outflow tract formation in distinct progenitor cells, and heparan sulfate
      modulates FGF signaling during early heart development. 

PMID- 26295703
TI  - Correction: Effects of Chronic Fluoxetine Treatment on Neurogenesis and
      Tryptophan Hydroxylase Expression in Adolescent and Adult Rats.

PMID- 26295702
TI  - Increased Stiffness in Aged Skeletal Muscle Impairs Muscle Progenitor Cell
      Proliferative Activity.
AB  - BACKGROUND: Skeletal muscle aging is associated with a decreased regenerative
      potential due to the loss of function of endogenous stem cells or myogenic
      progenitor cells (MPCs). Aged skeletal muscle is characterized by the deposition
      of extracellular matrix (ECM), which in turn influences the biomechanical
      properties of myofibers by increasing their stiffness. Since the stiffness of the
      MPC microenvironment directly impacts MPC function, we hypothesized that the
      increase in muscle stiffness that occurs with aging impairs the behavior of MPCs,
      ultimately leading to a decrease in regenerative potential. RESULTS: We showed
      that freshly isolated individual myofibers from aged mouse muscles contain fewer
      MPCs overall than myofibers from adult muscles, with fewer quiescent MPCs and
      more proliferative and differentiating MPCs. We observed alterations in cultured
      MPC behavior in aged animals, where the proliferation and differentiation of MPCs
      were lower and higher, respectively. These alterations were not linked to the
      intrinsic properties of aged myofibers, as shown by the similar values for the
      cumulative population-doubling values and fusion indexes. However, atomic force
      microscopy (AFM) indentation experiments revealed a nearly 4-fold increase in the
      stiffness of the MPC microenvironment. We further showed that the increase in
      stiffness is associated with alterations to muscle ECM, including the
      accumulation of collagen, which was correlated with higher hydroxyproline and
      advanced glycation end-product content. Lastly, we recapitulated the impaired MPC
      behavior observed in aging using a hydrogel substrate that mimics the stiffness
      of myofibers. CONCLUSIONS: These findings provide novel evidence that the low
      regenerative potential of aged skeletal muscle is independent of intrinsic MPC
      properties but is related to the increase in the stiffness of the MPC
      microenvironment.

PMID- 26295704
TI  - Domain III of Bacillus thuringiensis Cry1Ie Toxin Plays an Important Role in
      Binding to Peritrophic Membrane of Asian Corn Borer.
AB  - The insecticidal IE648 toxin is a truncated Cry1Ie protein with increased
      toxicity against Asian corn borer (ACB). Cry toxins are pore-forming toxins that
      disrupt insect midgut cells to kill the larvae. However, the peritrophic membrane
      (PM) is an important barrier that Cry toxins must cross before binding to midgut
      cells. Previously, it was shown that Cry toxins are able to bind and accumulate
      in the PM of several lepidopteran insects. Binding of IE648 toxin to PM of ACB
      was previously reported and the goal of the current work was the identification
      of the binding region between Cry1Ie and the PM of ACB. Homologous competition
      binding assays showed that this interaction was specific. Heterologous
      competition binding assays performed with different fragments corresponding to
      domain I, domain II and domain III allowed us to identify that domain III
      participates in the interaction of IE648 with the PM. Specifically, peptide D3-L8
      (corresponding to Cry1Ie toxin residues 607 to 616), located in an exposed loop
      region of domain III is probably involved in this interaction. Ligand blot assays
      show that IE648 interact with chitin and PM proteins with sizes of 30, 32 and 80
      kDa. The fact that domain III interacts with proteins of similar molecular masses
      supports that this region of the toxin might be involved in PM interaction. These
      data provide for the first time the identification of domain III as a putative
      binding region between PM and 3D-Cry toxin. 

PMID- 26295706
TI  - Towards Quantitative Optical Cross Sections in Entomological Laser Radar -
      Potential of Temporal and Spherical Parameterizations for Identifying Atmospheric
      Fauna.
AB  - In recent years, the field of remote sensing of birds and insects in the
      atmosphere (the aerial fauna) has advanced considerably, and modern electro-optic
      methods now allow the assessment of the abundance and fluxes of pests and
      beneficials on a landscape scale. These techniques have the potential to
      significantly increase our understanding of, and ability to quantify and manage,
      the ecological environment. This paper presents a concept whereby laser radar
      observations of atmospheric fauna can be parameterized and table values for
      absolute cross sections can be catalogued to allow for the study of focal species
      such as disease vectors and pests. Wing-beat oscillations are parameterized with
      a discrete set of harmonics and the spherical scatter function is parameterized
      by a reduced set of symmetrical spherical harmonics. A first order spherical
      model for insect scatter is presented and supported experimentally, showing
      angular dependence of wing beat harmonic content. The presented method promises
      to give insights into the flight heading directions of species in the atmosphere
      and has the potential to shed light onto the km-range spread of pests and disease
      vectors. 

PMID- 26295705
TI  - Detection of Human Papillomavirus DNA in Patients with Breast Tumor in China.
AB  - The presence of HPV in breast tissue and the potential causal association between
      human papillomavirus (HPV) and breast cancer (BC) remains controversial. The aim
      of the present study was to compare the HPV prevalence in BC tissues, adjacent
      normal breast tissues and breast benign disease tissues and to investigate the
      possible association between HPV and breast tumor development in Chinese women.
      Paraffin-embedded specimens from 187 pairs of BCs including tumor and normal
      breast tissue adjacent to tumors and 92 breast benign lesions between June 2009
      and July 2014 were investigated by nested polymerase chain reaction (PCR) and
      type-specific PCR, respectively. With strictly quality control, HPV positive
      infection was detected in three BC tissues. No HPV positive infection was
      detected in all normal breast tissue adjacent to tumors and benign breast
      tissues. Through our detailed analysis, rare HPV infection in this study suggests
      that HPV might not be associated with BC progression. 

PMID- 26295707
TI  - Disomic Inheritance and Segregation Distortion of SSR Markers in Two Populations
      of Cynodon dactylon (L.) Pers. var. dactylon.
AB  - Common bermudagrass [C. dactylon (L.) Pers. var. dactylon] is economically and
      environmentally the most important member among Cynodon species because of its
      extensive use for turf, forage and soil erosion control in the world. However,
      information regarding the inheritance within the taxon is limited. Accordingly,
      the objective of this study was to determine qualitative inheritance mode in
      common bermudagrass. Two tetraploid (2n = 4x = 36), first-generation selfed (S1)
      populations, 228 progenies of 'Zebra' and 273 from A12359, were analyzed for
      segregation with 21 and 12 simple sequence repeat (SSR) markers, respectively. It
      is concluded that the inheritance mode of tetraploid bermudagrass was complete or
      near complete disomic. It is evident that the two bermudagrass parents had an
      allotetraploid genome with two distinct subgenomes since 33 SSR primer pairs
      amplified 34 loci, each having two alleles. Severe transmission ratio distortions
      occurred in the Zebra population while less so in the A12359 population. The
      findings of disomic inheritance and segregation ratio distortion in common
      bermudagrass is significant in subsequent linkage map construction, quantitative
      trait locus mapping and marker-assisted selection in the species. 

PMID- 26295708
TI  - Effects of the Sequence of Isocaloric Meals with Different Protein Contents on
      Plasma Biochemical Indexes in Pigs.
AB  - Nutrient composition and pattern of food intake may play a significant role in
      weight gain. The aim of this study was to document the effects of a daily 3-meal
      pattern with isocaloric diets containing different dietary protein contents on
      growth performance and different plasma biochemical indexes including amino acid
      plasma concentration in castrated male pigs. Then, 21 DLY
      (Duroc*Landrace*Yorkshire) pigs aged 60 days were assigned randomly into 3
      groups: a control group (crude protein, CP 18.1%), a group receiving high then
      basal and then low CP meals (High-Low group) and a group receiving low then basal
      and then high CP meal (Low-High group) for 40 days with pigs being feed
      restricted. On day 40, after 12 h fasting, blood samples were obtained for
      analysis. The results showed that the insulin/glucagon ratio was lower in the
      High-Low group (P<0.05) when compared with the control group. Compared with the
      control group, the average daily gain of pigs from the High-Low group increased
      by 14.10% (P = 0.046). Compared with the control group, serum gamma-glutamyl
      transferase (GGT) decreased significantly (P<0.05) in both the High-Low and Low
      High groups. Plasma concentrations of branched-chain amino acids (BCAA: valine,
      isoleucine and leucine) increased in the Low-High group (P<0.05) when compared
      with the control group; and plasma methionine and serine decreased in both the
      two experimental groups (P<0.05). Compared with the High-Low group, all the BCAA
      increased significantly (P<0.05) in the Low-High group. These findings suggest
      that the sequence and quantity of alimentary protein intake affect the
      insulin/glucagon ratio, as well as amino acid concentrations including BCAA,
      methionine and serine. It is proposed that meal pattern with pigs receiving high
      then basal and then low CP meals daily may help to improve the weight gain of
      pigs. 

PMID- 26295709
TI  - Arming of MAIT Cell Cytolytic Antimicrobial Activity Is Induced by IL-7 and
      Defective in HIV-1 Infection.
AB  - Mucosa-associated invariant T (MAIT) cells represent a large innate-like
      evolutionarily conserved antimicrobial T-cell subset in humans. MAIT cells
      recognize microbial riboflavin metabolites from a range of microbes presented by
      MR1 molecules. MAIT cells are impaired in several chronic diseases including HIV
      1 infection, where they show signs of exhaustion and decline numerically. Here,
      we examined the broader effector functions of MAIT cells in this context and
      strategies to rescue their functions. Residual MAIT cells from HIV-infected
      patients displayed aberrant baseline levels of cytolytic proteins, and failed to
      mobilize cytolytic molecules in response to bacterial antigen. In particular, the
      induction of granzyme B (GrzB) expression was profoundly defective. The
      functionally impaired MAIT cell population exhibited abnormal T-bet and Eomes
      expression patterns that correlated with the deficiency in cytotoxic capacity and
      cytokine production. Effective antiretroviral therapy (ART) did not fully restore
      these aberrations. Interestingly, IL-7 was capable of arming resting MAIT cells
      from healthy donors into cytotoxic GrzB+ effector T cells capable of killing
      bacteria-infected cells and producing high levels of pro-inflammatory cytokines
      in an MR1-dependent fashion. Furthermore, IL-7 treatment enhanced the sensitivity
      of MAIT cells to detect low levels of bacteria. In HIV-infected patients, plasma
      IL-7 levels were positively correlated with MAIT cell numbers and function, and
      IL-7 treatment in vitro significantly restored MAIT cell effector functions even
      in the absence of ART. These results indicate that the cytolytic capacity in MAIT
      cells is severely defective in HIV-1 infected patients, and that the broad-based
      functional defect in these cells is associated with deficiency in critical
      transcription factors. Furthermore, IL-7 induces the arming of effector functions
      and enhances the sensitivity of MAIT cells, and may be considered in
      immunotherapeutic approaches to restore MAIT cells. 

PMID- 26295710
TI  - Amniotic Fluid Derived Stem Cells with a Renal Progenitor Phenotype Inhibit
      Interstitial Fibrosis in Renal Ischemia and Reperfusion Injury in Rats.
AB  - OBJECTIVES: Mesenchymal stem cells derived from human amniotic fluid (hAFSCs) are
      a promising source for cellular therapy, especially for renal disorders, as a
      subpopulation is derived from the fetal urinary tract. The purpose of this study
      was to evaluate if hAFSCs with a renal progenitor phenotype demonstrate a
      nephroprotective effect in acute ischemia reperfusion (I/R) model and prevent
      late stage fibrosis. METHODS: A total of 45 male 12-wk-old Wistar rats were
      divided into three equal groups;: rats subjected to I/R injury and treated with
      Chang Medium, rats subjected to I/R injury and treated with hAFSCs and sham
      operated animals. In the first part of this study, hAFSCs that highly expressed
      CD24, CD117, SIX2 and PAX2 were isolated and characterized. In the second part,
      renal I/R injury was induced in male rats and cellular treatment was performed 6
      hours later via arterial injection. Functional and histological analyses were
      performed 24 hours, 48 hours and 2 months after treatment using serum creatinine,
      urine protein to creatinine ratio, inflammatory and regeneration markers and
      histomorphometric analysis of the kidney. Statistical analysis was performed by
      analysis of variance followed by the Tukey's test for multiple comparisons or by
      nonparametric Kruskal-Wallis followed by Dunn. Statistical significance level was
      defined as p <0.05. RESULTS: hAFSCs treatment resulted in significantly reduced
      serum creatinine level at 24 hours, less tubular necrosis, less hyaline cast
      formation, higher proliferation index, less inflammatory cell infiltration and
      less myofibroblasts at 48 h. The treated group had less fibrosis and proteinuria
      at 2 months after injury. CONCLUSION: hAFSCs contain a renal progenitor cell
      subpopulation that has a nephroprotective effect when delivered intra-arterially
      in rats with renal I/R injury, and reduces interstitial fibrosis on long term
      follow-up.

PMID- 26295711
TI  - Risk of Developing Depressive Disorders following Hepatocellular Carcinoma: A
      Nationwide Population-Based Study.
AB  - BACKGROUND & AIMS: To evaluate the risk of depressive disorders among patients
      with Hepatocellular Carcinoma (HCC) using the National Health Insurance Research
      Database (NHIRD) in Taiwan. METHODS: We conducted a retrospective study of a
      newly diagnosed HCC cohort of 55,973 participants who were selected from the
      NHIRD. Patients were observed for a maximum of 6 years to determine the rates of
      newly onset depressive disorders, and Cox regression was used to identify the
      risk factors associated with depressive disorders in HCC patients. RESULTS: Of
      the total 55,973 HCC patients, 1,041 patients (1.86%) were diagnosed with
      depressive disorders during a mean (SD) follow-up period of 1.1 (1.2) years. The
      Cox multivariate proportional hazards analysis showed that age of 40-59 (HR
      1.376, 95% CI 1.049-1.805, p = 0.021), age of 60-79 (HR 1.341, 95% CI 1.025
      1.753, p = 0.032), women (HR 1.474 95% CI 1.301-1.669, p < 0.001), metastasis (HR
      1.916, 95% CI 1.243-2.953, p = 0.003), and HCV (HR 1.445, 95% CI 1.231-1.697, p <
      0.001) were independent risk factors for developing depressive disorders.
      CONCLUSIONS: Our study indicated a subsequent risk of depressive disorders in
      patients with HCC, and the risk increased for those with female gender, aged 40
      to 59, aged 60 to 79, with metastasis, or with HCV. Psychological evaluation and
      support are two critical issues in these HCC patients with the risk factors.

PMID- 26295713
TI  - In Vitro Validation of an Artefact Suppression Algorithm in X-Ray Phase-Contrast
      Computed Tomography.
AB  - X-ray phase-contrast tomography can significantly increase the contrast
      resolution of conventional attenuation-contrast imaging, especially for soft
      tissue structures that have very similar attenuation. Just as in attenuation
      based tomography, phase contrast tomography requires a linear dependence of
      aggregate beam direction on the incremental direction alteration caused by
      individual voxels along the path of the X-ray beam. Dense objects such as
      calcifications in biological specimens violate this condition. There are
      extensive beam deflection artefacts in the vicinity of such structures because
      they result in large distortion of wave front due to the large difference of
      refractive index; for such large changes in beam direction, the transmittance of
      the silicon analyzer crystal saturates and is no longer linearly dependent on the
      angle of refraction. This paper describes a method by which these effects can be
      overcome and excellent soft-tissue contrast of phase tomography can be preserved
      in the vicinity of such artefact-producing structures. 

PMID- 26295712
TI  - HdhQ111 Mice Exhibit Tissue Specific Metabolite Profiles that Include Striatal
      Lipid Accumulation.
AB  - The HTT CAG expansion mutation causes Huntington's Disease and is associated with
      a wide range of cellular consequences, including altered metabolism. The mutant
      allele is expressed widely, in all tissues, but the striatum and cortex are
      especially vulnerable to its effects. To more fully understand this tissue
      specificity, early in the disease process, we asked whether the metabolic impact
      of the mutant CAG expanded allele in heterozygous B6.HdhQ111/+ mice would be
      common across tissues, or whether tissues would have tissue-specific responses
      and whether such changes may be affected by diet. Specifically, we cross
      sectionally examined steady state metabolite concentrations from a range of
      tissues (plasma, brown adipose tissue, cerebellum, striatum, liver, white adipose
      tissue), using an established liquid chromatography-mass spectrometry pipeline,
      from cohorts of 8 month old mutant and wild-type littermate mice that were fed
      one of two different high-fat diets. The differential response to diet
      highlighted a proportion of metabolites in all tissues, ranging from 3% (7/219)
      in the striatum to 12% (25/212) in white adipose tissue. By contrast, the mutant
      CAG-expanded allele primarily affected brain metabolites, with 14% (30/219) of
      metabolites significantly altered, compared to wild-type, in striatum and 11%
      (25/224) in the cerebellum. In general, diet and the CAG-expanded allele both
      elicited metabolite changes that were predominantly tissue-specific and non
      overlapping, with evidence for mutation-by-diet interaction in peripheral tissues
      most affected by diet. Machine-learning approaches highlighted the accumulation
      of diverse lipid species as the most genotype-predictive metabolite changes in
      the striatum. Validation experiments in cell culture demonstrated that lipid
      accumulation was also a defining feature of mutant HdhQ111 striatal progenitor
      cells. Thus, metabolite-level responses to the CAG expansion mutation in vivo
      were tissue specific and most evident in brain, where the striatum featured
      signature accumulation of a set of lipids including sphingomyelin,
      phosphatidylcholine, cholesterol ester and triglyceride species. Importantly, in
      the presence of the CAG mutation, metabolite changes were unmasked in peripheral
      tissues by an interaction with dietary fat, implying that the design of studies
      to discover metabolic changes in HD mutation carriers should include metabolic
      perturbations. 

PMID- 26295715
TI  - Attitudes towards evaluation of psychiatric disability claims: a survey of Swiss
      stakeholders.
AB  - QUESTIONS: In Switzerland, evaluation of work capacity in individuals with mental
      disorders has come under criticism. We surveyed stakeholders about their concerns
      and expectations of the current claim process. METHODS: We conducted a nationwide
      online survey among five stakeholder groups. We asked 37 questions addressing the
      claim process and the evaluation of work capacity, the maximum acceptable
      disagreement in judgments on work capacity, and its documentation. RESULTS:
      Response rate among 704 stakeholders (95 plaintiff lawyers, 285 treating
      psychiatrists, 129 expert psychiatrists evaluating work capacity, 64 social
      judges, 131 insurers) varied between 71% and 29%. Of the lawyers, 92% were
      dissatisfied with the current claim process, as were psychiatrists (73%) and
      experts (64%), whereas the majority of judges (72%) and insurers (81%) were
      satisfied. Stakeholders agreed in their concerns, such as the lack of a
      transparent relationship between the experts' findings and their conclusions
      regarding work capacity, medical evaluations inappropriately addressing legal
      issues, and the experts' delay in finalising the report. Findings mirror the
      characteristics that stakeholders consider important for an optimal work capacity
      evaluation. For a scenario where two experts evaluate the same claimant,
      stakeholders considered an inter-rater difference of 10%-20% in work capacity at
      maximum acceptable. CONCLUSIONS: Plaintiff lawyers, treating psychiatrists and
      experts perceive major problems in work capacity evaluation of psychiatric claims
      whereas judges and insurers see the process more positively. Efforts to improve
      the process should include clarifying the basis on which judgments are made,
      restricting judgments to areas of expertise, and ensuring prompt submission of
      evaluations.

PMID- 26295714
TI  - Biophysical Characterization of Essential Phosphorylation at the Flexible C
      Terminal Region of C-Raf with 14-3-3zeta Protein.
AB  - Phosphorylation at the C-terminal flexible region of the C-Raf protein plays an
      important role in regulating its biological activity. Auto-phosphorylation at
      serine 621 (S621) in this region maintains C-Raf stability and activity. This
      phosphorylation mediates the interaction between C-Raf and scaffold protein 14-3
      3zeta to activate the downstream MEK kinase pathway. In this study, we have
      defined the interaction of C-terminal peptide sequence of C-Raf with 14-3-3zeta
      protein and determined the possible structural adaptation of this region.
      Biophysical elucidation of the interaction was carried out using phosphopeptide
      (residue number 615-630) in the presence of 14-3-3zeta protein. Using isothermal
      titration calorimetry (ITC), a high binding affinity with micro-molar range was
      found to exist between the peptide and 14-3-3zeta protein, whereas the non
      phosphorylated peptide did not show any appreciable binding affinity. Further
      interaction details were investigated using several biophysical techniques such
      as circular dichroism (CD), fluorescence, and nuclear magnetic resonance (NMR)
      spectroscopy, in addition to molecular modeling. This study provides the
      molecular basis for C-Raf C-terminal-derived phosphopeptide interaction with 14-3
      3zeta protein as well as structural insights responsible for phosphorylated S621
      mediated 14-3-3zeta binding at an atomic resolution. 

PMID- 26295717
TI  - Targeting mitochondrial metal dyshomeostasis for the treatment of
      neurodegeneration.
AB  - Mitochondrial impairment and metal dyshomeostasis are suggested to be associated
      with many neurodegenerative disorders including Alzheimer's disease, Parkinson's
      disease, Huntington's disease, amyotrophic lateral sclerosis and Friedreich's
      ataxia. Treatments aimed at restoring metal homeostasis are highly effective in
      models of these diseases, and clinical trials hold promise. However, in general,
      the effect of these treatments on mitochondrial metal homeostasis is unclear, and
      the contribution of mitochondrial metal dyshomeostasis to disease pathogenesis
      requires further investigation. This review describes the role of metals in
      mitochondria in health, how mitochondrial metals are disrupted in
      neurodegenerative diseases, and potential therapeutics aimed at restoring
      mitochondrial metal homeostasis and function. 

PMID- 26295716
TI  - The Formin Diaphanous Regulates Myoblast Fusion through Actin Polymerization and
      Arp2/3 Regulation.
AB  - The formation of multinucleated muscle cells through cell-cell fusion is a
      conserved process from fruit flies to humans. Numerous studies have shown the
      importance of Arp2/3, its regulators, and branched actin for the formation of an
      actin structure, the F-actin focus, at the fusion site. This F-actin focus forms
      the core of an invasive podosome-like structure that is required for myoblast
      fusion. In this study, we find that the formin Diaphanous (Dia), which nucleates
      and facilitates the elongation of actin filaments, is essential for Drosophila
      myoblast fusion. Following cell recognition and adhesion, Dia is enriched at the
      myoblast fusion site, concomitant with, and having the same dynamics as, the F
      actin focus. Through analysis of Dia loss-of-function conditions using mutant
      alleles but particularly a dominant negative Dia transgene, we demonstrate that
      reduction in Dia activity in myoblasts leads to a fusion block. Significantly, no
      actin focus is detected, and neither branched actin regulators, SCAR or WASp,
      accumulate at the fusion site when Dia levels are reduced. Expression of
      constitutively active Dia also causes a fusion block that is associated with an
      increase in highly dynamic filopodia, altered actin turnover rates and F-actin
      distribution, and mislocalization of SCAR and WASp at the fusion site. Together
      our data indicate that Dia plays two roles during invasive podosome formation at
      the fusion site: it dictates the level of linear F-actin polymerization, and it
      is required for appropriate branched actin polymerization via localization of
      SCAR and WASp. These studies provide new insight to the mechanisms of cell-cell
      fusion, the relationship between different regulators of actin polymerization,
      and invasive podosome formation that occurs in normal development and in disease.

PMID- 26295718
TI  - Care considerations for dementia in people with Down's syndrome: a management
      perspective.
AB  - Dementia is common in people with Down's syndrome as they age. Having dementia
      raises huge care considerations for carers and staff. Excellence in care requires
      attention to a wide variety of interrelated issues. Carers and staff need to have
      a good understanding of what it means to have dementia to deliver person-centered
      care. In addition, they need to be clear at all stages of the disease about the
      outcomes they want to achieve for the person. This will necessitate taking into
      account both health and social care issues, as well as looking at the physical
      environment. Staffing and staff training are crucial in providing the right
      support at the right time. Finally, a vignette of excellence in care is
      presented. 

PMID- 26295719
TI  - Managing psychosis in Parkinson's disease without drugs.

PMID- 26295720
TI  - Piramal Imaging.
AB  - Piramal Imaging, a division of Piramal Enterprises Ltd, is a global
      radiopharmaceutical company that is actively developing novel PET radiotracers
      for use in molecular imaging. The company focuses on developing innovative
      products that improve early detection and characterization of chronic and life
      threatening diseases, leading to better therapeutic outcomes and improved quality
      of life. 

PMID- 26295721
TI  - Outcome measurement in neurodegenerative disease: attributes, applications &
      interpretation.
AB  - There has been a marked shift from clinically assessed to patient assessed
      outcomes of treatment in neurodegenerative conditions over recent decades. The
      use of patient-reported outcome measures (PROMs) provides a method with which
      researchers and clinicians can gain insightful and meaningful data on health
      status from the patients' perspective. It is imperative that high-quality PROMs
      are chosen based upon their measurement properties and their suitability for use
      in the intended clinical or research context. This review aims to give a brief
      overview of best practice standards for selecting PROMs, current instruments used
      in exemplar neurodegenerative conditions and their application in clinical trials
      and routine measurement. 

PMID- 26295722
TI  - Completed suicide in a case of clinically diagnosed progressive supranuclear
      palsy.
AB  - We present the clinical history and the cognitive and behavioral presentations of
      a male patient with suspected progressive supranuclear palsy (PSP) who fatally
      shot himself in the head. We believe his act of suicide was the consequence of
      impulsivity, rather than primary depression or mood disturbance. In cases of
      suspected PSP and other atypical parkinsonisms, health professionals must be
      aware of neurobehavioral risk factors for suicide attempts and completions to
      promote patient safety; however, the literature on this topic is sparse. Our case
      highlights the potentially lethal consequences of impulsivity and other
      neuropsychiatric symptoms in PSP and related syndromes. 

PMID- 26295723
TI  - Systematic review of planned care transitions for persons with dementia.
AB  - A systematic review was conducted to identify, categorize and summarize available
      research on planned care transitions or relocations for persons with dementia
      (PWD) in order to help guide best practice. Articles were identified by keyword
      searches of electronic databases, and a soft search of references of relevant
      articles. The review found that planned care transitions in PWD are associated
      with an increase in undesirable outcomes, particularly immediately post
      transition, and that caregivers are often underutilized in care planning and
      underprepared for care transitions. It is recommended that transitional care
      interventions for PWD make explicit efforts to enhance caregiver involvement,
      provide social and pragmatic support for PWD and their caregivers and offer
      assistance in managing behavioral and psychological symptoms of dementia. 

PMID- 26295724
TI  - Role of socioeconomic position in multiple sclerosis etiology.
AB  - Multiple sclerosis (MS) is a debilitating autoimmune disease with a prominent
      inflammatory component. There have been strides identifying genetic and
      environmental MS risk factors, though much of the disease risk remains unknown.
      Recent large observational studies suggest adverse socioeconomic position
      increases the risk for MS, however the mediating biological processes are not
      understood. We hypothesize a prominent role for stress response, both the
      autonomic nervous system and the hypothalamic-pituitary-adrenal axis, which
      become maladaptive under frequent or chronic stimulation resulting in a
      proinflammatory phenotype. Thus, adverse SEP and chronic stress may predispose
      individuals for MS. 

PMID- 26295726
TI  - Unpredictable sensations: can stochastic resonance help in Parkinson's disease?

PMID- 26295727
TI  - Incorporating real-world clinical practice in multiple sclerosis economic
      evaluations.
AB  - Using evidence from short-term randomized controlled trials, decision-analytic
      models project costs, risks and benefits of disease-modifying therapies (DMTs)
      for multiple sclerosis (MS). Such trial-informed models lack the breadth needed
      to generalize to clinical practice or policy due to limitations: lack of DMT
      switching/discontinuation, limited head-to-head DMT comparisons and efficacy, not
      effectiveness, designs. We present an illustrative example that incorporates
      treatment switching and discontinuation by estimating the cost-effectiveness
      (value) of first-line natalizumab versus second-line natalizumab treatment for
      relapsing-remitting MS patients negative for anti-JC virus antibodies. Treating
      JC virus-negative relapsing-remitting MS patients with natalizumab as first-line
      provided better value compared with second-line. Decision-makers should consider
      this evidence for treatment step-edit policies through modeling scenarios closer
      to clinical practice. 

PMID- 26295728
TI  - Telepain Management of Phantom Limb Pain Using Mirror Therapy.
AB  - BACKGROUND: In response to rising healthcare costs and the social and economic
      burden of outpatient rehabilitation services, telepain management has emerged as
      an exciting alternative method of clinical care. Patients with limb amputations
      who experience phantom limb pain (PLP) are typically treated unsuccessfully using
      medications, injections, or additional surgeries. Mirror therapy is a
      noninvasive, cost-effective alternative to current treatment options for PLP.
      PATIENTS AND METHODS: We report 2 patients who self-administered mirror therapy
      at home after receiving detailed instructions from a physician by e-mail.
      RESULTS: The intervention resulted in complete resolution of PLP. The first
      patient experienced a reduction in the severity and frequency of PLP episodes
      after 4 weeks of treatment. Pain completely resolved after an additional 4 weeks
      of treatment, which was restarted 4 months after the initial course of therapy.
      The second patient experienced complete eradication of pain after 4 weeks of
      treatment. CONCLUSIONS: PLP relief can be obtained using home-based mirror
      therapy with initiation, feedback, and follow-up with healthcare professionals
      conducted entirely through telemedicine.

PMID- 26295729
TI  - Functional inactivation of lymphocytes by methylene blue with visible light.
AB  - Transfusion of allogeneic white blood cells (WBCs) may cause adverse reactions in
      immunocompromised recipients, including transfusion-associated graft-versus-host
      disease (TA-GVHD), which is often fatal and incurable. In this study, the in
      vitro effect of methylene blue with visible light (MB + L) treatment on
      lymphocyte proliferation and cytokine production was measured to investigate
      whether MB + L can be used to prevent immune reactions that result from
      transfused lymphocytes. WBCs and 3 MUM of MB were mixed and transferred into
      medical PVC bags, which were then exposed to visible light. Gamma irradiation was
      conducted as a parallel positive control. The cells without treatment were used
      as untreated group. All the groups were tested for the ability of cell
      proliferation and cytokine production upon stimulation. After incubation with
      mitogen phytohemagglutinin (PHA) or plate-bound anti-CD3 plus anti-CD28, the
      proliferation of MB + L/gamma-irradiation treated lymphocytes was significantly
      inhibited (P < 0.01) as compared to the untreated ones; the proliferation
      inhibitive rate of the MB + L group was even higher than that of gamma-irradiated
      cells (73.77% +/- 28.75% vs. 44.72% +/- 38.20%). MB + L treated cells incubated
      up to 7 days with PHA also showed no significant proliferation. The levels of TNF
      alpha, IFN-gamma, IL-6, IL-8, IL-10 and IL-1beta present in the supernatant of MB
      + L treated lymphocytes upon stimulation were significantly lower than those of
      untreated lymphocytes. These results demonstrated that MB + L treatment
      functionally and irreversibly inactivated lymphocytes by inhibiting lymphocyte
      proliferation and the production of cytokines. MB + L treatment might be a
      promising method for the prevention of adverse immune responses caused by WBCs. 

PMID- 26295730
TI  - Feasibility and Acceptability of a Pilot Housing Transition Program for Homeless
      Adults with Mental Illness and Substance Use.
AB  - The purpose of this study was to determine if a housing transition program was
      feasible and acceptable to homeless clients with mental illness and substance use
      histories. Ten male residents of a homeless shelter participated in the 3-week
      housing intervention. The intervention used a DVD format with instructional
      videos, graphics, and opportunities for hands-on practice of functional skills in
      a simulated apartment environment. Outcome measures included goal attainment
      scale scores (GAS), satisfaction surveys, and case manager reports. Six of the 10
      participants completed the program and achieved GAS scores at a greater level
      than expected at baseline (T > 50). Participants reported the intervention to be
      engaging and enhanced their knowledge of the housing transition process. The
      intervention appears to have assisted the participants in the attainment of
      housing skills and warrants further study. 

PMID- 26295731
TI  - Lenalidomide monotherapy leads to a complete remission in refractory B-cell post
      transplant lymphoproliferative disorder.

PMID- 26295733
TI  - Molecular Dynamics Simulations of Perylenediimide DNA Base Surrogates.
AB  - Perylene-3,4,9,10-tetracarboxylic diimides (PTCDIs) are a well-known class of
      organic materials. Recently, these molecules have been incorporated within DNA as
      base surrogates, finding ready applications as probes of DNA structure and
      function. However, the assembly dynamics and kinetics of PTCDI DNA base
      surrogates have received little attention to date. Herein, we employ constant
      temperature molecular dynamics simulations to gain an improved understanding of
      the assembly of PTCDI dimers and trimers. We also use replica-exchange molecular
      dynamics simulations to elucidate the energetic landscape dictating the formation
      of stacked PTCDI structures. Our studies provide insight into the equilibrium
      configurations of multimeric PTCDIs and hold implications for the construction of
      DNA-inspired systems from perylene-derived organic semiconductor building blocks.

PMID- 26295732
TI  - Saline in acute bronchiolitis RCT and economic evaluation: hypertonic saline in
      acute bronchiolitis - randomised controlled trial and systematic review.
AB  - BACKGROUND: Acute bronchiolitis is the most common cause of hospitalisation in
      infancy. Supportive care and oxygen are the cornerstones of management. A
      Cochrane review concluded that the use of nebulised 3% hypertonic saline (HS) may
      significantly reduce the duration of hospitalisation. OBJECTIVE: To test the
      hypothesis that HS reduces the time to when infants were assessed as being fit
      for discharge, defined as in air with saturations of > 92% for 6 hours, by 25%.
      DESIGN: Parallel-group, pragmatic randomised controlled trial, cost-utility
      analysis and systematic review. SETTING: Ten UK hospitals. PARTICIPANTS: Infants
      with acute bronchiolitis requiring oxygen therapy were allocated within 4 hours
      of admission. INTERVENTIONS: Supportive care with oxygen as required, minimal
      handling and fluid administration as appropriate to the severity of the disease,
      3% nebulised HS every +/- 6 hours. MAIN OUTCOME MEASURES: The trial primary
      outcome was time until the infant met objective discharge criteria. Secondary end
      points included time to discharge and adverse events. The costs analysed related
      to length of stay (LoS), readmissions, nebulised saline and other NHS resource
      use. Quality-adjusted life-years (QALYs) were estimated using an existing utility
      decrement derived for hospitalisation in children, together with the time spent
      in hospital in the trial. DATA SOURCES: We searched MEDLINE, EMBASE, the Cochrane
      Central Register of Controlled Trials and other databases from inception or from
      2010 onwards, searched ClinicalTrials.gov and other registries and hand-searched
      Chest, Paediatrics and Journal of Paediatrics to January 2015. REVIEW METHODS: We
      included randomised/quasi-randomised trials which compared HS versus saline (+/-
      adjunct treatment) or no treatment. We used a fixed-effects model to combine mean
      differences for LoS and assessed statistical heterogeneity using the I (2)
      statistic. RESULTS: The trial randomised 158 infants to HS (n = 141 analysed) and
      159 to standard care (n = 149 analysed). There was no difference between the two
      arms in the time to being declared fit for discharge [median 76.6 vs. 75.9 hours,
      hazard ratio (HR) 0.95, 95% confidence interval (CI) 0.75 to 1.20] or to actual
      discharge (median 88.5 vs. 88.7 hours, HR 0.97, 95% CI 0.76 to 1.23). There was
      no difference in adverse events. One infant developed bradycardia with
      desaturation associated with HS. Mean hospital costs were L2595 and L2727 for the
      control and intervention groups, respectively (p = 0.657). Incremental QALYs were
      0.0000175 (p = 0.757). An incremental cost-effectiveness ratio of L7.6M per QALY
      gained was not appreciably altered by sensitivity analyses. The systematic review
      comprised 15 trials (n = 1922) including our own. HS reduced the mean LoS by 
      0.36 days (95% CI -0.50 to -0.22 days). High levels of heterogeneity (I (2) =
      78%) indicate that the result should be treated cautiously. CONCLUSIONS: In this
      trial, HS had no clinical benefit on LoS or readiness for discharge and was not a
      cost-effective treatment for acute bronchiolitis. Claims that HS achieves small
      reductions in LoS must be treated with scepticism. FUTURE WORK: Well-powered
      randomised controlled trials of high-flow oxygen are needed. STUDY REGISTRATION:
      This study is registered as NCT01469845 and CRD42014007569. FUNDING DETAILS: This
      project was funded by the NIHR Health Technology Assessment (HTA) programme and
      will be published in full in Health Technology Assessment; Vol. 19, No. 66. See
      the HTA programme website for further project information.

PMID- 26295734
TI  - Review of Ingested and Aspirated Foreign Bodies in Children and Their Clinical
      Significance for Radiologists.
AB  - Ingested and aspirated foreign bodies are a common occurrence in children and are
      important causes of morbidity and mortality in the pediatric population. Imaging
      plays an important role in the diagnosis of ingested and aspirated foreign bodies
      in children and can be crucial to guiding the clinical management of these
      patients. Prompt identification and localization of ingested foreign bodies is
      essential to determining the appropriate treatment, as several types of commonly
      ingested foreign bodies require urgent removal and others can be managed
      conservatively. In particular, disk batteries impacted in the esophagus carry a
      high risk of esophageal injury or perforation; multiple ingested magnets can
      become attracted to each other across bowel walls and cause bowel perforation and
      fistula formation; and sharp objects commonly cause complications as they pass
      through the gastrointestinal tract. Accordingly, these ingested foreign bodies
      warrant aggressive clinical management and therefore radiologists must be
      familiar with their imaging appearances and clinical implications. Prompt
      recognition of secondary radiographic signs of foreign-body aspiration is also
      crucial, as clinical symptoms can sometimes be nonspecific and most aspirated
      foreign bodies are radiolucent. Overall, radiography is the most important
      modality in the evaluation of ingested or aspirated foreign bodies; however,
      fluoroscopy and computed tomography play an ancillary role in complicated cases.
      It is essential that every radiologist who interprets imaging examinations of
      children be aware of the imaging appearances of commonly ingested and aspirated
      foreign bodies and their clinical significance.

PMID- 26295735
TI  - In Vivo Syndesmotic Overcompression After Fixation of Ankle Fractures With a
      Syndesmotic Injury.
AB  - OBJECTIVES: The goals of this study were to assess syndesmotic reductions using
      computerized tomography and to determine whether malreductions are associated
      with certain injury types or reduction forceps. DESIGN: Prospective cohort.
      SETTING: Urban level 1 trauma center. PATIENTS: Twenty-seven patients with
      operatively treated syndesmotic injuries were recruited prospectively.
      INTERVENTION: Patients underwent postoperative bilateral computerized tomography
      of the ankle and hindfoot to assess syndesmotic reduction. The uninjured
      extremity was used as a control. MAIN OUTCOME MEASUREMENT: Side-to-side
      differences of the fibular position within the tibial incisura were measured at
      several anatomic points and analyzed based on injury type, the presence of
      posterior malleolar injury, level of fracture, and type of reduction forceps
      used. RESULTS: On average, operatively treated syndesmotic injuries were
      overcompressed (fibular medialization) by 1 mm (P < 0.001) and externally rotated
      by 5 degrees  (P = 0.002) when compared with the uninjured extremity. The absence
      of a posterior malleolar injury and Weber B (OTA 44-B) fractures seemed to have a
      protective effect against malrotation, but not against overcompression. There was
      no difference in malreduction based on the type of the clamp used. CONCLUSIONS:
      It is possible, and highly likely based on these data, to overcompress the
      syndesmosis when using reduction forceps. Care should be taken to avoid
      overcompression, as this may affect the ankle motion and functional outcomes. To
      our knowledge, this is the first in vivo series of syndesmotic overcompression.
      LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a
      complete description of levels of evidence.

PMID- 26295736
TI  - Does the Fibula Need to be Fixed in Complex Pilon Fractures?
AB  - OBJECTIVES: To review a series of patients with complex plafond injuries with a
      metadiaphyseal dissociation who did not have the fibula fixed and compare with
      patients who had their fibula fixed using patients without a fibula fracture as a
      control group. DESIGN: Retrospective case-control study. SETTING: Level 1 Trauma
      center at a university hospital. PATIENTS/PARTICIPANTS: Skeletally mature
      patients with a complete metadiaphyseal plafond fracture, and adequate
      presentation, postreduction, and healed radiographs to measure varus and valgus
      alignment. INTERVENTION: Surgical treatment [external fixator or open reduction
      internal fixation (ORIF)] of high energy pilon fractures. MAIN OUTCOME
      MEASUREMENTS: Metaphyseal alignment at the time of presentation, after fixation,
      and at union, surgical procedures performed, and complications. METHODS: From 364
      patients with plafond fractures, 111 had high energy injuries with metadiaphyseal
      dissociation and form the basis of the study. Radiographs and charts were
      reviewed for fracture characteristics, metaphyseal alignment at the time of
      presentation, after fixation, and at union, surgical procedures performed, and
      complications. RESULTS: Of the 111 study patients, 93 patients were treated
      definitively with ORIF of the tibia and 18 patients were treated definitively in
      an external fixator. Within the 93 patients treated definitively with ORIF of the
      tibia, we identified 3 groups of patients those with a fibula fracture that was
      fixed (26 patients), those with a fibula fracture that was not fixed (37
      patients), and those without a fibula fracture acting as the control group (30
      patients). Between the 2 groups having a fibula fracture treated with ORIF of the
      tibia, there was no difference in fibula fracture pattern or location. For the 26
      patients who had fibular fixation, it was performed in 11 patients at an average
      of 17 days for inability to hold length and alignment and in 15 patients to
      augment fixation in poor bone stock or to aid in the reduction. Patients with
      initial valgus deformity were more likely to have their fibula fixed. There was
      no difference in the postoperative or final alignment between the patients with
      fibula fractures (with or without fixation) and those without fibula fractures (P
      = 0.92). When comparing the 3 groups, the only statistical finding between the 2
      groups was that those with fibula fixation required plate removal (P < 0.0001).
      CONCLUSIONS: Fibular fixation is not a necessary step in the reconstruction of
      pilon fractures, although it may be helpful in specific cases to aid in tibial
      plafond reduction or augment external fixation. We found a higher rate of plate
      removal if the fibula was fixed. LEVEL OF EVIDENCE: Therapeutic Level III. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 26295737
TI  - BMP-7 and Bone Regeneration: Evaluation of Dose-Response in a Rodent Segmental
      Defect Model.
AB  - OBJECTIVES: To develop and validate a translatable and reproducible rodent
      critical-sized defect (CSD) model and to determine the optimal dose of
      recombinant human bone morphogenetic protein (BMP)-7 required to consistently
      heal the CSD in the new model. METHODS: Rats with 6-mm CSDs stabilized with a
      commercial radiolucent plate and screws with angular stability were randomly
      assigned to 4 treatment groups with varied doses of recombinant human BMP-7 (25,
      50, 75, and 100 MUg) on absorbable collagen sponge and a single control group
      (absorbable collagen sponge alone). Bone formation was evaluated by radiographs,
      micro-computed tomography, histology, and biomechanics. RESULTS: All the rats
      treated with 100 MUg of BMP-7 with CSDs were united by 4 weeks and all 75- and 50
      MUg-group rats united by 6 weeks. None of the animals in the 25-MUg BMP-7 group
      or the control group were healed at the time of killing. Bone volume, bone
      mineral density, the ratio of bone volume to total volume, stiffness, and
      ultimate load to failure were maximal in the 50-MUg group. Total callus volume
      progressively increased with increasing BMP dose. Histologic analysis
      demonstrated increased callus width with increasing BMP-7 doses above 50 MUg, but
      the bone seemed structurally abnormal. CONCLUSIONS: There was a 100% union rate
      in the 50-, 75-, and 100-MUg BMP-7-treated groups. None of the control or 25-MUg
      dose rats united. The biomechanical data demonstrated that 50 MUg of BMP-7
      produced the highest mechanical strength in the bone regenerate. These data also
      suggest that administration of BMP-7 above 50 MUg does not improve bone
      regeneration and actually seems to produce lower quality bone with diminished
      biomechanical properties.

PMID- 26295738
TI  - To the Editor.

PMID- 26295739
TI  - In Response.

PMID- 26295740
TI  - In Response.

PMID- 26295741
TI  - The Influence of the Expression of Subtle and Blatant Sexual Prejudice on
      Personal Prejudice and Identification With the Expresser.
AB  - Although the negative consequences of subtle and blatant prejudice for the
      targets of prejudice are clear in the psychological literature, the impact of
      exposure to subtle and blatant prejudice on non-targets remains unclear. The
      current work examines how exposure to blatant and subtle sexual prejudice affects
      non-targets' personal endorsement of prejudice and their identification with the
      prejudice expresser. Results suggest that relative to exposure to blatant or
      neutral expressions of prejudice, exposure to subtle prejudice increased
      prejudice levels. Individuals were also more likely to distance from the
      prejudice expresser when exposed to blatant compared to subtle prejudice. The
      implications are discussed. 

PMID- 26295742
TI  - Platelet Lipidomic Profiling: Novel Insight into Cytosolic Phospholipase A2alpha
      Activity and Its Role in Human Platelet Activation.
AB  - With a newer, more selective and efficacious cytosolic phospholipase A2alpha
      (cPLA2alpha) inhibitor available, we revisited the role of cPLA2alpha activity in
      platelet activation and discovered that a component of platelet signaling, even
      larger than previously appreciated, relies on this enzyme. In a whole blood shear
      based flow chamber assay, giripladib, a cPLA2alpha inhibitor, reduced platelet
      adhesion and accumulation on collagen. Moreover, giripladib differentially
      affected P-selectin expression and GPIIbIIIa activation depending on the agonist
      employed. While protease-activated receptor 1 (PAR1)-mediated platelet activation
      was unaffected by giripladib, the levels of PAR4- and GPVI-mediated platelet
      activation were significantly reduced. Meanwhile, the thromboxane A2 receptor
      antagonist SQ29548 had no effect on PAR-, GPVI-, or puriniergic receptor-mediated
      platelet activation, suggesting that another eicosanoid produced downstream of
      arachidonic acid liberation by cPLA2alpha was responsible for this large
      component of PAR4- and GPVI-mediated platelet activation. In parallel, we
      profiled PAR-mediated changes in glycerophospholipid (GPL) mass with and without
      giripladib to better understand cPLA2alpha-mediated lipid metabolism.
      Phosphatidylcholine and phosphatidylethanolamine (PE) demonstrated the largest
      consumption of mass during thrombin stimulation. Additionally, we confirm
      phosphatidylinositol as a major substrate of cPLA2alpha. A comparison of PAR1-
      and PAR4-induced metabolism revealed the consumption of more putative arachidonyl
      PE species downstream of PAR1 activation. Instead of enhanced cPLA2alpha activity
      and therefore more arachidonic acid liberation downstream of PAR4, these results
      indicate the major role that cPLA2alpha activity plays in platelet function and
      suggest that a novel eicosanoid is produced in response to platelet activation
      that represents a large component of PAR4- and GPVI-mediated responses. 

PMID- 26295743
TI  - Automated Glycan Assembly of Oligosaccharides Related to Arabinogalactan
      Proteins.
AB  - Arabinogalactan proteins are heavily glycosylated proteoglycans in plants. Their
      glycan portion consists of type-II arabinogalactan polysaccharides whose
      heterogeneity hampers the assignment of the arabinogalactan protein function.
      Synthetic chemistry is key to the procurement of molecular probes for plant
      biologists. Described is the automated glycan assembly of 14 oligosaccharides
      from four monosaccharide building blocks. These linear and branched glycans
      represent key structural features of natural type-II arabinogalactans and will
      serve as tools for arabinogalactan biology. 

PMID- 26295744
TI  - Extracting the normal lung dose-response curve from clinical DVH data: a possible
      role for low dose hyper-radiosensitivity, increased radioresistance.
AB  - In conventionally fractionated radiation therapy for lung cancer, radiation
      pneumonitis' (RP) dependence on the normal lung dose-volume histogram (DVH) is
      not well understood. Complication models alternatively make RP a function of a
      summary statistic, such as mean lung dose (MLD). This work searches over damage
      profiles, which quantify sub-volume damage as a function of dose. Profiles that
      achieve best RP predictive accuracy on a clinical dataset are hypothesized to
      approximate DVH dependence.Step function damage rate profiles R(D) are generated,
      having discrete steps at several dose points. A range of profiles is sampled by
      varying the step heights and dose point locations. Normal lung damage is the
      integral of R(D) with the cumulative DVH. Each profile is used in conjunction
      with a damage cutoff to predict grade 2 plus (G2+) RP for DVHs from a University
      of Michigan clinical trial dataset consisting of 89 CFRT patients, of which 17
      were diagnosed with G2+ RP.Optimal profiles achieve a modest increase in
      predictive accuracy--erroneous RP predictions are reduced from 11 (using MLD) to
      8. A novel result is that optimal profiles have a similar distinctive shape:
      enhanced damage contribution from low doses (<20 Gy), a flat contribution from
      doses in the range ~20-40 Gy, then a further enhanced contribution from doses
      above 40 Gy. These features resemble the hyper-radiosensitivity / increased
      radioresistance (HRS/IRR) observed in some cell survival curves, which can be
      modeled using Joiner's induced repair model.A novel search strategy is employed,
      which has the potential to estimate RP dependence on the normal lung DVH. When
      applied to a clinical dataset, identified profiles share a characteristic shape,
      which resembles HRS/IRR. This suggests that normal lung may have enhanced
      sensitivity to low doses, and that this sensitivity can affect RP risk.

PMID- 26295745
TI  - A Reappraisal of the Minimum Duration of Antibiotic Treatment Before Approval of
      Return to School for Children With Streptococcal Pharyngitis.
AB  - OBJECTIVE: To determine whether a single dose of amoxicillin administered to a
      symptomatic child with confirmed strep throat might allow the child to return to
      school as little as 12 hours later. METHODS: We enrolled 111 evaluable children
      with sore throat plus a positive streptococcal rapid antigen detection test
      (RADT) as well as a positive result for group A Streptococci (GAS). After throat
      swab specimens were obtained, all participants received a single dose of
      amoxicillin (50 mg/kg). Twelve to 23 hours after the first dose of amoxicillin,
      all participants returned in the morning of day 2 for a second throat swab
      specimen. At the day 2 visit, a nurse or medical assistant obtained an interval
      history, tympanic membrane temperature, and a pediatrician or nurse practitioner
      examined the oropharynx. RESULTS: On the morning of day 2, only 10 of 111
      participants continued to have a positive RADT result, confirmed by overnight
      throat culture. GAS were not detectable on the day 2 throat specimen by RADT and
      also by culture in 91% of the study participants (confidence interval: 86-96%).
      Seven of 10 failures had a marked decrease in number of beta-hemolytic colonies,
      which were 3+ to 4+ on the initial overnight culture plate and decreased to 1+ on
      the follow-up (obtained on day 2) throat culture plate. Two participants
      continued to have 3+ or 4+ GAS after incubation of the second throat culture
      specimen. CONCLUSIONS: Even in the late afternoon, a full dose of amoxicillin (50
      mg/kg) administered after notification of positive RADT results for GAS resulted
      in nondetection of GAS in 91% of children the next morning. All children treated
      with amoxicillin for "strep throat" by 5 PM of day 1 may, if afebrile and
      improved, attend school on day 2.

PMID- 26295746
TI  - Natural beta-Dihydroagarofuran-Type Sesquiterpenoids as Cognition-Enhancing and
      Neuroprotective Agents from Medicinal Plants of the Genus Celastrus.
AB  - Alzheimer's disease (AD) is an irreversible, multifaceted, and progressive
      neurodegenerative disorder. Over the past 30 years, the search for anti-AD drugs
      has been primarily based on the cholinergic deficiency hypothesis and/or the beta
      amyloid (Abeta) cascade hypothesis. In this study, we report the identification
      of 16 new and 38 known beta-dihydroagarofuran-type sesquiterpenoids from
      Celastrus flagellaris and Celastrus angulatus. The beta-dihydroagarofuran-type
      sesquiterpenoids 58, 59, 61, and 63 significantly attenuated scopolamine-induced
      prolonged escape latency and increased number of errors compared with the control
      group. At 10 MUM, 21 of the 62 tested beta-dihydroagarofuran-type
      sesquiterpenoids rescued Abeta25-35-induced SH-SY5Y cells from viability
      reduction, which increased the cell viability from 64.6% for the model to more
      than 74.0%. The majority of the beta-dihydroagarofuran-type sesquiterpenoids with
      ester groups exhibited stronger activity than those with free hydroxy groups or
      without substituents at the same positions. These results identified a new
      chemical skeleton as drug lead for the investigation of novel therapeutic agents
      against AD. 

PMID- 26295748
TI  - Structural Transition in Layered As(1-x)P(x) Compounds: A Computational Study.
AB  - As a way to further improve the electronic properties of group V layered
      semiconductors, we propose to form in-layer 2D heterostructures of black
      phosphorus and gray arsenic. We use ab initio density functional theory to
      optimize the geometry, determine the electronic structure, and identify the most
      stable allotropes as a function of composition. Because pure black phosphorus and
      pure gray arsenic monolayers differ in their equilibrium structure, we predict a
      structural transition and a change in frontier states, including a change from a
      direct-gap to an indirect-gap semiconductor, with changing composition. 

PMID- 26295747
TI  - Antidepressant Use in the Elderly Is Associated With an Increased Risk of
      Dementia.
AB  - A retrospective cohort study was conducted including 3688 patients age 60 years
      or older without dementia enrolled in a depression screening study in primary
      care clinics. Information on antidepressant use and incident dementia during
      follow-up was retrieved from electronic medical records. The Cox proportional
      hazard models were used to compare the risk for incident dementia among 5
      participant groups: selective serotonin re-uptake inhibitors (SSRI) only, non
      SSRI only (non-SSRI), mixed group of SSRI and non-SSRI, not on antidepressants
      but depressed, and not on antidepressants and not depressed. SSRI and non-SSRI
      users had significantly higher dementia risk than the nondepressed nonusers
      (hazard ratio [HR]=1.83, P=0.0025 for SSRI users and HR=1.50, P=0.004 for non
      SSRI users). In addition, SSRIs users had significantly higher dementia risk than
      non-users with severe depression (HR=2.26, P=0.0005). Future research is needed
      to confirm our results in other populations and to explore potential mechanism
      underlying the observed association.

PMID- 26295749
TI  - Population vulnerability to storm surge flooding in coastal Virginia, USA.
AB  - This study aims to assess the vulnerability of populations to storm surge
      flooding in 12 coastal localities of Virginia, USA. Population vulnerability is
      assessed by way of 3 physical factors (elevation, slope, and storm surge
      category), 3 built-up components (road availability, access to hospitals, and
      access to shelters), and 3 household conditions (storm preparedness, financial
      constraints to recovering from severe weather events, and health fragility).
      Fuzzy analysis is used to generate maps illustrating variation in several types
      of population vulnerability across the region. When considering physical factors
      and household conditions, the most vulnerable neighborhoods to sea level rise and
      storm surge flooding are largely found in urban areas. However, when considering
      access to critical infrastructure, we find rural residents to be more vulnerable
      than nonrural residents. These detailed assessments can inform both local and
      state governments in catastrophic planning. In addition, the methodology may be
      generalized to assess vulnerability in other coastal corridors and communities.
      The originality is highlighted by evaluating socioeconomic conditions at refined
      scale, incorporating a broader range of human perceptions and predispositions,
      and employing a geoinformatics approach combining physical, built-up, and
      socioeconomic conditions for population vulnerability assessment. Integr Environ
      Assess Manag 2016;12:500-509. (c) 2015 SETAC. 

PMID- 26295750
TI  - Tramadol-induced hyperalgesia and its prevention by ketamine in rats: A
      randomised experimental study.
AB  - BACKGROUND: Opioid analgesia not only reduces inhalational anaesthetic
      requirements but may also induce delayed hyperalgesia, with potential effects on
      the minimum alveolar concentration (MAC) of inhalational anaesthetics.
      OBJECTIVES: The objective of this study was to evaluate the development of
      tramadol-induced hyperalgesia and the associated changes in MAC, and whether
      ketamine prevents both processes. DESIGN: A randomised, experimental study.
      SETTING: Experimental Surgery Unit, La Paz University Hospital, Madrid, Spain.
      ANIMALS: Thirty-nine adult male Wistar rats. INTERVENTIONS: Mechanical
      nociceptive thresholds (MNT) were determined up to 21 days after the
      intraperitoneal administration of a single dose of tramadol (50 mg kg) with or
      without ketamine (10 mg kg), or 0.9% saline. The MNT and the MAC of sevoflurane
      were also assessed in a second experiment before, early (30 min) and 7 days after
      drug administration with the same treatments. MAIN OUTCOME MEASURES: The MAC and
      MNT were evaluated. The analysis of variance (ANOVA) test was employed to
      determine differences between treatments and times on MAC and MNT. RESULTS:
      Tramadol, alone or combined with ketamine, produced an early increase in MNT.
      However, tramadol given alone decreased MNT from day 1 up to 3 weeks, which was
      associated with an increase in the MAC of sevoflurane (P < 0.05; day 7). Ketamine
      administration prevented both the reduction in MNT and the increase in MAC (P >
      0.05). CONCLUSION: Tramadol-induced hyperalgesia in the rat lasted for several
      weeks and was associated with an increase in the MAC of sevoflurane. Prior
      administration of ketamine blocked both phenomena.

PMID- 26295752
TI  - Effects of water management practices on residue decomposition and degradation of
      Cry1Ac protein from crop-wild Bt rice hybrids and parental lines during winter
      fallow season.
AB  - Rice is the staple diet of over half of the world's population and Bacillus
      thuringiensis (Bt) rice expressing insecticidal Cry proteins is ready for
      deployment. An assessment of the potential impact of Bt rice on the soil
      ecosystem under varied field management practices is urgently required. We used
      litter bags to assess the residue (leaves, stems and roots) decomposition
      dynamics of two transgenic rice lines (Kefeng6 and Kefeng8) containing stacked
      genes from Bt and sck (a modified CpTI gene encoding a cowpea trypsin inhibitor)
      (Bt/CpTI), a non-transgenic rice near-isoline (Minghui86), wild rice (Oryza
      rufipogon) and crop-wild Bt rice hybrid under contrasting conditions (drainage or
      continuous flooding) in the field. No significant difference was detected in the
      remaining mass, total C and total N among cultivars under aerobic conditions,
      whereas significant differences in the remaining mass and total C were detected
      between Kefeng6 and Kefeng8 and Minghui86 under the flooded condition. A higher
      decomposition rate constant (km) was measured under the flooded condition
      compared with the aerobic condition for leaf residues, whereas the reverse was
      observed for root residues. The enzyme-linked immunosorbent assay (ELISA), which
      was used to monitor the changes in the Cry1Ac protein in Bt rice residues,
      indicated that (1) the degradation of the Cry1Ac protein under both conditions
      best fit first-order kinetics, and the predicted DT50 (50% degradation time) of
      the Cry1Ac protein ranged from 3.6 to 32.5 days; (2) the Cry1Ac protein in the
      residue degraded relatively faster under aerobic conditions; and (3) by the end
      of the study (~154 days), the protein was present at a low concentration in the
      remaining residues under both conditions. The degradation rate constant was
      negatively correlated with the initial carbon content and positively correlated
      with the initial Cry1Ac protein concentration, but it was only correlated with
      the mass decomposition rate constants under the flooded condition. No Cry1Ac
      protein was detected in the soils surrounding the buried residue. Our results did
      not reveal any evidence that the stacked genes (Bt/CpTI) or the presence of the
      Cry1Ac protein influenced the decomposition dynamics of the rice residues.
      Furthermore, our results suggested that field drainage after residue
      incorporation would promote Cry1Ac protein degradation. 

PMID- 26295753
TI  - Histopathological changes in snail, Pomacea canaliculata, exposed to sub-lethal
      copper sulfate concentrations.
AB  - The acute toxicity test of Cu including range-finding and definitive test, was
      performed on golden apple snails, Pomacea canaliculata. The median lethal
      concentrations (LC50) of Cu at exposure times of 24, 48, 72 and 96 h were 330,
      223, 177 and 146 ug/L, respectively. P. canaliculata were exposed to Cu at 146
      ug/L for 96 h to study bioaccumulation and histopathological alterations in
      various organs. Snails accumulated elevated levels of Cu in gill, and lesser
      amounts in the digestive tract, muscle, and digestive gland. Histopathological
      investigation revealed several alterations in the epithelia of gill, digestive
      tract (esophagus, intestine, rectum), and digestive gland. The most striking
      changes were observed in the epithelium of the gill in which there was loss of
      cilia, an increase in number of mucus cells, and degeneration of columnar cells.
      Similar changes occurred in digestive tract epithelium. The digestive gland
      showed moderate alterations, vacuolization and degeneration of cells and an
      increase in the number of basophilic cells. We concluded that, P. canaliculata
      has a great potential as a bioindicator for Cu, and a biomarker for monitoring Cu
      contamination in aquatic environment.

PMID- 26295751
TI  - Mechanisms of BK virus infection of renal cells and therapeutic implications.
AB  - BK virus (BKV) causes BKV nephritis in renal transplant patients and contributes
      significantly to the increase of probability of graft loss. BKV, being latent in
      the urogenital tract, is likely to be transported with the donor kidney to
      recipients and following reactivation replicates in the nucleus of renal
      epithelial tubular cells. BKV daughter viruses are released and enter other renal
      epithelial cells to spread infection. There are still a lot of unknown factors
      about the mechanism and kinetics of BKV infection. The treatment of BKV
      infection, with exception of reduction in immunosuppression which increases the
      risk of allograft rejection, is almost exclusively limited to application of anti
      viral drugs with rather inconsistent results. The shortcomings of anti-viral
      therapies demand the understanding of early steps of infection of permissive
      cells by BK virus in hope that adequate interventional therapies preventing
      infection of cells with BK virus could be developed. This review describes the
      BKV entry in target human cells, intracellular trafficking pathways of BKV
      particles and potential therapeutic implications based on understanding of
      mechanisms of BKV infection of renal cells. 

PMID- 26295754
TI  - Utilizing the Infant's Capacity to Smell to Mitigate Painful Procedures.

PMID- 26295755
TI  - Innovative Approach for Interim Facial Prosthesis Using Digital Technology.
AB  - Despite the important role of facial prosthetic treatment in the rehabilitation
      of head and neck cancer patients, delay in its implementation can be unavoidable,
      preventing patients from receiving a prompt facial prosthesis and resuming a
      normal social life. Here, we introduce an innovative method for the fabrication
      of an interim facial prosthesis. Using a 3D modeling system, we simplified the
      fabrication method and used a titanium reconstruction plate for facial prosthesis
      retention. The patient received the facial prosthesis immediately after surgery
      and resumed a normal social life earlier than is typically observed with
      conventional facial prosthetic treatment. 

PMID- 26295756
TI  - A New Class of Ionic Liquids: Anion Amphiprotic Ionic Liquids.
AB  - We here present a new class of protic ionic liquids, anion amphiprotic ionic
      liquids (AAILs). These materials are protonation equilibrium free protic ionic
      liquids and interesting in their own right by not following the classical
      Bronsted acid-base neutralization concept. Due to the very simple synthesis route
      applied and their stable basic chemistry, we believe in a potential use for
      manifold applications. This is supported by the combination of practical material
      properties, foremost, a general intrinsic stability versus reversal of the
      formation reaction toward neutral species, broad liquidus ranges, long-term
      thermal stabilities, high conductivities, protic characteristics, and a general
      stability versus water. 

PMID- 26295757
TI  - Vibrational Circular Dichroism Shows Reversible Helical Handedness Switching in
      Peptidomimetic l-Valine Fibrils.
AB  - We elucidate the supramolecular organization in the form of microsize fibrils of
      gels formed by a l-Valine peptidomimetic compound. Analysis was based on circular
      dichroism spectroscopies, vibrational (VCD) and electronic (CD), supported by
      microscopy (atomic force and scanning electron). We show how the VCD spectra give
      account of the micrometric structure of the fibrils formed by the helicoidal
      arrangement of simpler proto-fibrils, which are organized in a lower hierarchical
      level. This ability is used to monitorize a fully reversible change in the
      handedness of the helix by modulating different external stimuli as pH or ionic
      strength, thus providing the first observation by VCD of such a phenomenon in a
      short peptide. 

PMID- 26295758
TI  - Investigation of Nanoscale Interactions by Means of Subharmonic Excitation.
AB  - Multifrequency atomic force microscopy holds promise as a method to provide
      qualitative and quantitative information about samples with high spatial
      resolution. Here, we provide experimental evidence of the excitation of
      subharmonics in ambient conditions in the regions where capillary interactions
      are predicted to be the mechanism of excitation. We also experimentally decouple
      a second mechanism for subharmonic excitation that is highly independent of
      environmental conditions such as relative humidity. This implies that material
      properties could be mapped. Subharmonic excitation could lead to experimental
      determination of surface water affinity in the nanoscale whenever water
      interactions are the mechanism of excitation. 

PMID- 26295759
TI  - Unexpected Molecular Sieving Properties of Zeolitic Imidazolate Framework-8.
AB  - We studied molecular sieving properties of zeolitic imidazolate framework-8 (ZIF
      8) by estimating the thermodynamically corrected diffusivities of probe molecules
      at 35  degrees C. From helium (2.6 A) to iso-C4H10 (5.0 A), the corrected
      diffusivity drops 14 orders of magnitude. Our results further suggest that the
      effective aperture size of ZIF-8 for molecular sieving is in the range of 4.0 to
      4.2 A, which is significantly larger than the XRD-derived value (3.4 A) and
      between the well-known aperture size of zeolite 4A (3.8 A) and 5A (4.3 A).
      Interestingly, because of aperture flexibility, the studied C4 hydrocarbon
      molecules that are larger than this effective aperture size still adsorb in the
      micropores of ZIF-8 with kinetic selectivities for iso-C4H8/iso-C4H10 of 180 and
      n-C4H10/iso-C4H10 of 2.5 * 10(6). These unexpected molecular sieving properties
      open up new opportunities for ZIF materials for separations that cannot be
      economically achieved by traditional microporous adsorbents such as synthetic
      zeolites. 

PMID- 26295760
TI  - Understanding the Origins of Dipolar Couplings and Correlated Motion in the
      Vibrational Spectrum of Water.
AB  - The combination of vibrational spectroscopy and molecular dynamics simulations
      provides a powerful tool to obtain insights into the molecular details of water
      structure and dynamics in the bulk and in aqueous solutions. Applying newly
      developed approaches to analyze correlations of charge currents, molecular dipole
      fluctuations, and vibrational motion in real and k-space, we compare results from
      nonpolarizable water models, widely used in biomolecular modeling, to ab initio
      molecular dynamics. For the first time, we unfold the infrared response of bulk
      water into contributions from correlated fluctuations in the three-dimensional,
      anisotropic environment of an average water molecule, from the OH-stretching
      region down to the THz regime. Our findings show that the absence of electronic
      polarizability in the force field model not only results in differences in
      dipolar couplings and infrared absorption but also induces artifacts into the
      correlated vibrational motion between hydrogen-bonded water molecules,
      specifically at the intramolecular bending frequency. Consequently, vibrational
      motion is partially ill-described with implications for the accuracy of non-self
      consistent, a posteriori methods to add polarizability. 

PMID- 26295761
TI  - Pushing the Limit of Infrared Multiphoton Dissociation to Megadalton-Size DNA
      Ions.
AB  - We report the use of infrared multiphoton dissociation (IRMPD) for the
      determination of relative activation energies for unimolecular dissociation of
      megadalton DNA ions. Single ions with masses in the megadalton range were stored
      in an electrostatic ion trap for a few tens of milliseconds and the image current
      generated by the roundtrips of ions in the trap was recorded. While being
      trapped, single ions were irradiated by a CO2 laser and fragmented, owing to
      multiphoton IR activation. The analysis of the single-ion image current during
      the heating period allows us to measure changes in the charge of the trapped ion.
      We estimated the activation energy associated with the dissociation of megadalton
      size DNA ions in the frame of an Arrhenius-like model by analyzing a large set of
      individual ions in order to construct a frequency histogram of the dissociation
      rates for a collection of ions. 

PMID- 26295762
TI  - First-Principles Computational Modeling of Fluorescence Resonance Energy Transfer
      in Co-Sensitized Dye Solar Cells.
AB  - TiO2 cosensitization by different dyes having complementary absorption represents
      an appealing strategy to obtain panchromatic sensitization in dye-sensitized
      solar cells. Fluorescence (Foster) resonance energy transfer (FRET) from an
      energy relay dye to a sensitizing dye, both grafted onto TiO2, was effectively
      shown to produce additional photocurrent (Hardin et al. J. Am. Chem. Soc.2011,
      133, 10662). Here we develop a realistic cosensitization model to provide a
      precise estimate of the geometrical parameters, which govern the FRET rate. The
      reliability of our model is fully confirmed by the quantitative reproduction of
      the experimental spectral shift in the naphtalocyanine absorption band and by the
      excellent agreement between the experimentally reported FRET rates. Our model
      provides a realistic picture of the cosensitized TiO2 interface and is capable,
      at the same time, of predicting the cosensitization mechanism and the associated
      FRET kinetics based on the sole photophysical characterization of the isolated
      donor/acceptor partners. 

PMID- 26295763
TI  - High-Pressure Phase Favored by a Symmetry-Recognized Nanoconfinement Effect.
AB  - Recently, a high-pressure phase (B2) of KI has been experimentally observed in
      the inner space of single-walled carbon nanotubes. Our first-principles
      calculations indicate that in a confined nanospace, relative stabilities of the
      high-pressure B2 phase and the low-pressure B1 phase of KI are not necessarily
      determined by their external pressures. As a result of crystal symmetry
      differences, different phases are preferred at different K/I ratios. Such a
      symmetry-recognized confinement effect opens a new avenue for nanomaterials
      synthesis. 

PMID- 26295764
TI  - Mechanisms of Defect Generation and Clustering in CH3S Self-Assembled Monolayers
      on Au(111).
AB  - Periodic density functional calculations probe that step edges play a key role as
      source of defects during self-assembly. It is shown that the self-assembly
      process strongly reduces the energy required to strip an atom from the gold
      surface, locally increasing the concentration of surface defects. The
      thermodynamic driving force for the atom stripping is considerably more favorable
      along step-edge lines within the self-assembly than on the higher-coordinated
      terrace sites. Furthermore, the clustering of surface defects is considered, and
      we probe that the formation of aggregates of vacancies in the form of vacancy
      pits significantly stabilizes the self-assembly on the terraces of gold, where
      the role of the step edges is expected to be less significant. The high stability
      of pit-like structures arises from a balance between the corrugation and the
      enhanced bonding of defect-rich substrates. Our results demonstrate the important
      role that step edges play during assembly and could be very valuable for
      discovering defect-free assembled structures. 

PMID- 26295765
TI  - Nitrogen-Doped Carbon Nanotube/Graphite Felts as Advanced Electrode Materials for
      Vanadium Redox Flow Batteries.
AB  - Nitrogen-doped carbon nanotubes have been grown, for the first time, on graphite
      felt (N-CNT/GF) by a chemical vapor deposition approach and examined as an
      advanced electrode for vanadium redox flow batteries (VRFBs). The unique porous
      structure and nitrogen doping of N-CNT/GF with increased surface area enhances
      the battery performance significantly. The enriched porous structure of N-CNTs on
      graphite felt could potentially facilitate the diffusion of electrolyte, while
      the N-doping could significantly contribute to the enhanced electrode
      performance. Specifically, the N-doping (i) modifies the electronic properties of
      CNT and thereby alters the chemisorption characteristics of the vanadium ions,
      (ii) generates defect sites that are electrochemically more active, (iii)
      increases the oxygen species on CNT surface, which is a key factor influencing
      the VRFB performance, and (iv) makes the N-CNT electrochemically more accessible
      than the CNT. 

PMID- 26295766
TI  - Alcohol Dehydration on Monooxo W?O and Dioxo O?W?O Species.
AB  - The dehydration of 1-propanol on nanoporous WO3 films prepared via ballistic
      deposition at ~20 K has been investigated using temperature-programmed
      desorption, infrared reflection absorption spectroscopy, and density functional
      theory. The as-deposited films are extremely efficient in 1-propanol dehydration
      to propene. This activity is correlated with the presence of dioxo O?W?O groups,
      whereas monooxo W?O species are shown to be inactive. Annealing of the films
      induces densification that results in the loss of catalytic activity due to the
      annihilation of O?W?O species. 

PMID- 26295767
TI  - Understanding the Interface Dipole of Copper Phthalocyanine (CuPc)/C60: Theory
      and Experiment.
AB  - Interface dipole determines the electronic energy alignment in donor/acceptor
      interfaces and plays an important role in organic photovoltaics. Here we present
      a study combining first principles density functional theory (DFT) with
      ultraviolet photoemission spectroscopy (UPS) and time-of-flight secondary ion
      mass spectrometry (TOF-SIMS) to investigate the interface dipole, energy level
      alignment, and structural properties at the interface between CuPc and C60. DFT
      finds a sizable interface dipole for the face-on orientation, in quantitative
      agreement with the UPS measurement, and rules out charge transfer as the origin
      of the interface dipole. Using TOF-SIMS, we show that the interfacial morphology
      for the bilayer CuPc/C60 film is characterized by molecular intermixing,
      containing both the face-on and the edge-on orientation. The complementary
      experimental and theoretical results provide both insight into the origin of the
      interface dipole and direct evidence for the effect of interfacial morphology on
      the interface dipole. 

PMID- 26295768
TI  - Chiral-Induced Spin Selectivity Effect.
AB  - The chiral-induced spin selectivity (CISS) effect was recently established
      experimentally and theoretically. Here, we review some of the new findings and
      discuss applications that can result from special properties of this effect, like
      the reduction of the elastic backscattering in electron transfer through chiral
      molecules. The CISS effect opens the possibility of using chiral molecules in
      spintronics applications and for providing a deeper understanding of spin
      selective processes in biology. 

PMID- 26295769
TI  - Quantum-Dot-Based (Aero)gels: Control of the Optical Properties.
AB  - In this work, we have developed novel hybrid quantum dot gels based on the
      controllable and reversible assembly of nanoparticles via metal-tetrazole
      complexation. Combining in one hybrid network nanocrystals of different
      semiconductors (ZnSe and CdTe) as well as quantum dots of different sizes (green
      and red emitting CdTe) with different band gaps, we have examined energy
      relations within these systems and act out a facile route to the color design of
      the resulting gels. Efficient energy pumping from donor quantum dots to acceptors
      leads to a remarkable enhancement of the emission intensity of the gel.
      Furthermore, by integrating three different quantum dot types into one network,
      we obtained a white-light-emitting aerogel. 

PMID- 26295770
TI  - CO Oxidation at the Interface between Doped CeO2 and Supported Au Nanoclusters.
AB  - DFT+U calculations of CO oxidation by Au13 nanoclusters (NCs) supported on either
      CeO2 or doped (X-Ce)O2 (X = Au, Pt, Pd, Ti, Ru, Zr) show that doping the CeO2
      support accelerates CO oxidation by the Mars-van Krevelen mechanism at the Au-(X
      Ce)O2 interface. We find that Au, Pd, Pt, and Ti dopants significantly lower the
      vacancy formation energy of the CeO2 support and that electron donation from the
      supported Au13 NC shifts the vacancy formation energy of (X-Ce)O2 and determines
      the final vacancy formation energy of Au13@(X-Ce)O2. The vacancy formation energy
      of Au13@(X-Ce)O2 is a good reactivity descriptor for CO oxidation at the Au-(X
      Ce)O2 interface and a screening factor for dopant selection. Our results confirm
      that the catalytic activity of oxide-supported Au catalysts can be modified by
      the chemical composition of the support and suggest that chemical modification of
      the oxide support is promising for the optimization of oxidation catalysis by
      supported Au NCs/nanoparticles. 

PMID- 26295771
TI  - Nanostructured Scrolls from Graphene Oxide for Microjet Engines.
AB  - Layered heterostructures containing graphene oxide (GO) nanosheets and 20-35 nm
      bimetal coatings can detach easily from a Si substrate upon sonication
      spontaneously forming freestanding, micrometer-sized scrolls with GO on the
      outside-due to a combination of material stresses and weak bonding between GO
      layers. Simple procedures can tune the scroll diameters by varying the
      thicknesses of the metal films, and these results are confirmed by both
      experiment and modeling. The selection of materials determines the stresses that
      control the rolling behavior, as well as the functionality of the structures. In
      the GO/Ti/Pt system, the Pt is located within the interior of the scrolls, which
      can become self-propelled microjet engines through O2 bubbling when suspended in
      aqueous H2O2. 

PMID- 26295772
TI  - Effect of Copper Doping on Electronic Structure, Geometric Structure, and
      Stability of Thiolate-Protected Au25 Nanoclusters.
AB  - Several recent studies have attempted to impart [Au25(SR)18](-) with new
      properties by doping with foreign atoms. In this study, we studied the effect of
      copper doping on the electronic structure, geometric structure, and stability of
      [Au25(SR)18](-) with the aim of investigating the effect of foreign atom doping
      of [Au25(SR)18](-). CunAu25-n(SC2H4Ph)18 was synthesized by reducing complexes
      formed by the reaction between metal salts (copper and gold salts) and PhC2H4SH
      with NaBH4. Mass analysis revealed that the products contained CunAu25
      n(SC2H4Ph)18 (n = 1-5) in high purity. Experimental and theoretical analysis of
      the synthesized clusters revealed that copper doping alters the optical
      properties and redox potentials of the cluster, greatly distorts its geometric
      structure, and reduces the cluster stability in solution. These findings are
      expected to be useful for developing design guidelines for functionalizing
      [Au25(SR)18](-) through doping with foreign atoms. 

PMID- 26295773
TI  - Direct Measurement of Single CdSe Nanowire Extinction Polarization Anisotropies.
AB  - The origin of sizable absorption polarization anisotropies (rhoabs) in one
      dimensional (1D) semiconductor nanowires (NWs) has been debated. Invoked
      explanations employ either classical or quantum mechanical origins, where the
      classical approach suggests dielectric constant mismatches between the NW and its
      surrounding environment as the predominant source of observed polarization
      sensitivities. At the same time, the confinement-influenced mixing of states
      suggests a sizable contribution from polarization-sensitive transition selection
      rules. Sufficient evidence exists in the literature to support either claim.
      However, in all cases, these observations stem from excitation polarization
      anisotropy (rhoexc) studies, which only indirectly measure rhoabs. In this
      manuscript, we directly measure the band edge extinction polarization
      anisotropies (rhoext) of individual CdSe NWs using single NW extinction
      spectroscopy. Observed polarization anisotropies possess distinct spectral
      features and wavelength dependencies that correlate well with theoretical
      transition selection rules derived from a six-band k.p theory used to model the
      electronic structure of CdSe NWs. 

PMID- 26295774
TI  - Enhanced Li Adsorption and Diffusion on MoS2 Zigzag Nanoribbons by Edge Effects:
      A Computational Study.
AB  - By means of density functional theory computations, we systematically
      investigated the adsorption and diffusion of Li on the 2-D MoS2 nanosheets and 1
      D zigzag MoS2 nanoribbons (ZMoS2NRs), in comparison with MoS2 bulk. Although the
      Li mobility can be significantly facilitated in MoS2 nanosheets, their decreased
      Li binding energies make them less attractive for cathode applications. Because
      of the presence of unique edge states, ZMoS2NRs have a remarkably enhanced
      binding interaction with Li without sacrificing the Li mobility, and thus are
      promising as cathode materials of Li-ion batteries with a high power density and
      fast charge/discharge rates. 

PMID- 26295775
TI  - Catalytic Growth of Graphene: Toward Large-Area Single-Crystalline Graphene.
AB  - For electronic applications, synthesis of large-area, single-layer graphene with
      high crystallinity is required. One of the most promising and widely employed
      methods is chemical vapor deposition (CVD) using Cu foil/film as the catalyst.
      However, the CVD graphene is generally polycrystalline and contains a significant
      amount of domain boundaries that limit intrinsic physical properties of graphene.
      In this Perspective, we discuss the growth mechanism of graphene on a Cu catalyst
      and review recent development in the observation and control of the domain
      structure of graphene. We emphasize the importance of the growth condition and
      crystallinity of the Cu catalyst for the realization of large-area, single
      crystalline graphene. 

PMID- 26295777
TI  - Spin for Physical Chemists.

PMID- 26295776
TI  - Multiferroic and Magnetoelectric Oxides: The Emerging Scenario.
AB  - Multiferroics were considered to be rare because magnetism and ferroelectricity
      require entirely different criteria for the materials. Several multiferroic
      oxides have, however, been discovered in the past few years by virtue of novel
      operating mechanisms, the most effective one being ferroelectricity driven by
      magnetism itself. Many such oxides where the magnetic and electric order
      parameters interact also exhibit magnetoelectric or magnetodielectric properties.
      In this Perspective, properties of manganites, ferrites, and other monophasic
      multiferroic oxides with spin-induced electric polarization are described.
      Multiferroic properties arising from charge ordering are examined. The present
      status of BiMnO3, which is an unusual example of a ferromagnetic-ferroelectric,
      is presented. Recent findings suggest that it is likely that many more
      multiferroic and magnetoelectric oxide materials exhibiting magnetically induced
      ferroelectricity will be found in the future. 

PMID- 26295778
TI  - Practical Model for First Hyperpolarizability Dispersion Accounting for Both
      Homogeneous and Inhomogeneous Broadening Effects.
AB  - A practical yet accurate dispersion model for the molecular first
      hyperpolarizability beta is presented, incorporating both homogeneous and
      inhomogeneous line broadening because these affect the beta dispersion
      differently, even if they are indistinguishable in linear absorption.
      Consequently, combining the absorption spectrum with one free shape-determining
      parameter Ginhom, the inhomogeneous line width, turns out to be necessary and
      sufficient to obtain a reliable description of the beta dispersion, requiring no
      information on the homogeneous (including vibronic) and inhomogeneous line
      broadening mechanisms involved, providing an ideal model for practical use in
      extrapolating experimental nonlinear optical (NLO) data. The model is applied to
      the efficient NLO chromophore picolinium quinodimethane, yielding an excellent
      fit of the two-photon resonant wavelength-dependent data and a dependable static
      value beta0 = 316 * 10(-30) esu. Furthermore, we show that including a second
      electronic excited state in the model does yield an improved description of the
      NLO data at shorter wavelengths but has only limited influence on beta0. 

PMID- 26295779
TI  - Facilitating Minima Search for Large Water Clusters at the MP2 Level via
      Molecular Tailoring.
AB  - Water clusters (H2O)20 and (H2O)25 are explored at the Moller-Plesset second
      order perturbation (MP2) level of theory. Geometry optimization is carried out on
      favorable structures, initially generated by the temperature basin paving (TBP)
      method, utilizing the fragment-based molecular tailoring approach (MTA). MTA
      based stabilization energies at the complete basis set limit are accurately
      estimated by grafting the energy correction using a smaller basis set. For
      prototypical cases, the minima are established via MTA-based vibrational
      frequency calculations at the MP2/aug-cc-pVDZ level. The potential of MTA in
      tackling large clusters is further demonstrated by performing geometry
      optimization at MP2/aug-cc-pVDZ starting with the global minimum of (H2O)30
      reported by Monte Carlo (MC) and molecular dynamics (MD) investigations. The
      present study brings out the efficacy of MTA in performing computationally
      expensive ab initio calculations with minimal off-the-shelf hardware without
      significant loss of accuracy. 

PMID- 26295780
TI  - Non-Equilibrium Isomer Distribution of the Gas-Phase Photoactive Yellow Protein
      Chromophore.
AB  - The conjugate base of para-coumaric acid, which can be conveniently generated in
      the gas phase by electrospray ionization (ESI), is a commonly used model system
      for the chromophore of the photoactive yellow protein. Here we report its gas
      phase IR spectrum, which shows that the anion easily adopts a carboxylate
      structure lying 60 kJ/mol higher in energy than the global minimum phenoxide
      structure. Generation of the biologically more relevant phenoxide isomer by ESI
      can be achieved using dry acetonitrile as solvent. 

PMID- 26295781
TI  - [CTi7(2+)]: Heptacoordinate Carbon Motif?
AB  - A heptacoordinate carbon motif [CTi7(2+)] is predicted to be a highly stable
      structure (with D5h point group symmetry) based on ab initio computation. This
      motif possesses a sizable HOMO-LUMO gap along with the lowest vibrational
      frequency greater than 95 cm(-1). An investigation of the motif-containing
      neutral species [CTi7(2+)][BH4(-)]2 further confirms the chemical stability of
      the heptacoordinate carbon motif. In view of its structural stability, a quasi
      one-dimensional (quasi-1D) nanowire [CTi7]n[C16H8]n is built from the carbon
      motifs. This organometallic nanowire is predicted to be metallic based on density
      functional theory computation. 

PMID- 26295782
TI  - Origin of Optical Excitations in Fluorine-Doped Titania from Response Function
      Theory: Relevance to Photocatalysis.
AB  - We investigate the effect of fluorine doping on the optical spectra of
      stoichiometric and reduced TiO2 anatase, brookite, and rutile using density
      functional methods. The present approach is able to reproduce the main features
      of experiments and high-level quasiparticle calculations for undoped titania but
      at a much lower computational cost, thus allowing the study of doped titania,
      which requires large supercells. Whereas the simulated spectra of F-substituted
      brookite and rutile do not show any significant new feature, a relatively intense
      new band near the visible region is predicted for F-substituted anatase. This
      allows one to suggest assigning the spectral features near the visible region,
      observed on multiphase F-doped titania samples, to the presence of anatase. The
      physical origin of the new absorption band in F-doped anatase is unambiguously
      attributed to the presence of Ti(3+) centers. 

PMID- 26295783
TI  - CO2 Activation and Methanol Synthesis on Novel Au/TiC and Cu/TiC Catalysts.
AB  - Small Cu and Au particles in contact with a TiC(001) surface undergo a charge
      polarization that makes them very active for CO2 activation and the catalytic
      synthesis of methanol. The binding energy of CO2 on these systems is in the range
      of 0.6 to 1.1 eV, much larger than those observed on surfaces or nanoparticles of
      Cu and Au. Thus, in spite of the poor CO2 hydrogenation performance of Cu(111)
      and Au(111), the Cu/TiC(001) and Au/TiC(001) systems display a catalytic activity
      for methanol synthesis substantially higher than that of conventional Cu/ZnO
      catalysts. The turnover frequencies for methanol production on Cu/TiC(001) are
      170-500 times much larger than on Cu(111). The present study moves away from the
      typical approach of using metal/oxide catalysts for the synthesis of methanol via
      CO2 hydrogenation. This work shows that metal carbides can be excellent supports
      for enhancing the ability of noble metals to bond and activate CO2. 

PMID- 26295784
TI  - Ultrafast Studies of Exciton Migration and Polaron Formation in Sequentially
      Solution-Processed Conjugated Polymer/Fullerene Quasi-Bilayer Photovoltaics.
AB  - We examine the ultrafast dynamics of exciton migration and polaron production in
      sequentially processed 'quasi-bilayer' and preblended 'bulk heterojunction' (BHJ)
      solar cells based on conjugated polymer films that contain the same total amount
      of fullerene. We find that even though the polaron yields are similar, the
      dynamics of polaron production are significantly slower in quasi-bilayers than
      BHJs. We argue that the different polaron production dynamics result from the
      fact that (1) there is significantly less fullerene inside the polymer in quasi
      bilayers than in BHJs and (2) sequential processing yields polymer layers that
      are significantly more ordered than BHJs. We also argue that thermal annealing
      improves the performance of quasi-bilayer solar cells not because annealing
      drives additional fullerene into the polymer but because annealing improves the
      fullerene crystallinity. All of the results suggest that sequential processing
      remains a viable alternative for producing polymer/fullerene solar cells with a
      nanometer-scale architecture that differs from BHJs. 

PMID- 26295785
TI  - Tracking of Proton Transfer Reaction in Supercooled RNA Nucleoside.
AB  - In this paper we address a longstanding debate concerning the proton transfer
      reaction of DNA and RNA compounds. The sample tested is beta-uridine, one of the
      four basic components of RNA, which has been suggested to have the capacity to
      adopt lactam and lactim tautomeric forms. The essential biological importance of
      this RNA nucleoside has motivated a number of experimental and theoretical
      investigations in the past. However, the kinetics of the proton transfer reaction
      of this compound has not been examined. Herein, we employ dielectric spectroscopy
      and refractive index measurements to experimentally characterize lactam-lactim
      transformation in the supercooled liquid state. We quantify the kinetics of beta
      uridine tautomerization and suggest a mechanism for the configurational changes.
      The obtained data are compared to quantum chemical calculations. Finally the
      biological importance of our results is discussed. 

PMID- 26295786
TI  - Ultrafast Studies of the Photophysics of Cis and Trans States of the Green
      Fluorescent Protein Chromophore.
AB  - Cis-trans photoisomerization is proposed as a key process in the photoswitching
      of some photoactivatable fluorescent proteins. Here we present ultrafast
      fluorescence measurements of the model GFP chromophore (HBDI) in the cis state
      and in a mixture of the cis and trans states. Our results demonstrate that the
      mean lifetimes of the cis and trans states are remarkably similar. Therefore, the
      specific isomer of the chromophore cannot be solely responsible for the different
      photophysics of the bright and dark states of photoactive proteins, which must
      therefore be due to differential interactions between the different isomers of
      the chromophore and the protein. 

PMID- 26295787
TI  - Single-Molecule Surface-Enhanced Raman Scattering: Can STEM/EELS Image
      Electromagnetic Hot Spots?
AB  - Since the observation of single-molecule surface-enhanced Raman scattering
      (SMSERS) in 1997, questions regarding the nature of the electromagnetic hot spots
      responsible for such observations still persist. For the first time, we employ
      electron-energy-loss spectroscopy (EELS) in a scanning transmission electron
      microscope (STEM) to obtain maps of the localized surface plasmon modes of SMSERS
      active nanostructures, which are resolved in both space and energy. Single
      molecule character is confirmed by the bianalyte approach using two isotopologues
      of Rhodamine 6G. Surprisingly, the STEM/EELS plasmon maps do not show any direct
      signature of an electromagnetic hot spot in the gaps between the nanoparticles.
      The origins of this observation are explored using a fully three-dimensional
      electrodynamics simulation of both the electron-energy-loss probability and the
      near-electric field enhancements. The calculations suggest that electron beam
      excitation of the hot spot is possible, but only when the electron beam is
      located outside of the junction region. 

PMID- 26295788
TI  - Cervical cancer with paraaortic involvement: do patients truly benefit from
      tailored chemoradiation therapy? A retrospective study on 8 French centers.
AB  - We retrospectively studied the therapeutic significance of extended-field
      radiotherapy combined with concurrent platinum-based chemotherapy for the
      management of cervical carcinoma with paraaortic spread. Treatment response and
      survival outcomes were evaluated. One hundred and fifteen women were
      retrospectively studied. Radiological staging was conducted in 101 (87.8%)
      patients and paraaortic lymphadenectomy in 78 (67.8%). Patterns of treatment
      comprised chemoradiation therapy (100%), intracavitary brachytherapy (81.7%),
      completion surgery (60%) and neoadjuvant chemotherapy (4.3%). Four-year overall
      and disease-free survivals were 32.7% and 28.8%, respectively. Progression and
      relapse mostly involved the locoregional area and distant organs, rather than the
      paraaortic area. Advanced FIGO stage at baseline was the most significant
      prognostic factor (HR=3.02, p=0.01). Despite systematic extended-field
      chemoradiation therapy, paraaortic involvement in cervical cancer is associated
      with poor survival outcomes. The patterns of progression and recurrence suggest
      the existence of occult metastatic disease at presentation. Additional systemic
      treatment might thus be beneficial. 

PMID- 26295789
TI  - Effects of in utero cord blood collection on post-cesarean hemoglobin levels.
AB  - OBJECTIVE: To assess effects of in utero cord blood collection on postoperative
      hemoglobin, hematocrit levels. STUDY DESIGN: Elective cesarean deliveries in
      which cord blood was collected were compared with match paired elective cesarean
      deliveries without cord blood collection. Pre-post-operative hemoglobin and
      hematocrit level differences were compared between study groups with Student's t
      test. Multivariate regression models were used to address confounders.
      Correlation between volume of collected UCB and mean decrease in blood count
      parameters was analyzed. RESULTS: A total of 399 cesarean deliveries during a 12
      months period were included in the analysis. Mean decrease in hemoglobin levels
      was 1.08g/dL (SD=1.0) in UCB collected group compared to 0.84g/dL (SD=1.0) in
      control group (p=0.002). Mean decrease in hematocrit levels was 3.1% (SD=3.4) in
      cord blood collected cesarean delivery group compared to 1.9% (SD=2.4) in control
      group (p=0.002). Univariate analysis has shown the collected UCB volume to be
      uncorrelated with the change in hemoglobin levels (r=0.013). Multivariate
      regression models, after adjusting for birth weight, age and number of prior
      cesarean, have shown the UCB collection to be significantly associated with the
      mean decrease in blood count parameters (estimate=0.23g/dL, t=-2.23, p=0.02).
      CONCLUSION: In utero UCB collection is associated with a small increase in
      bleeding of little clinical importance. Amount of UCB is not associated with
      amount of change in hemoglobin and hematocrit levels. In utero UCB collection
      seems to be safe for expectant mothers scheduled for low-risk cesarean delivery.

PMID- 26295790
TI  - Outcomes of women with gestational diabetes mellitus in Sweden.
AB  - OBJECTIVE: The number of women with gestational diabetes mellitus (GDM) during
      pregnancy is increasing around the world and in our region in the south Sweden
      1.2% of all pregnant women received the GDM diagnosis in the 90s and now it is
      about 2.2%. The aim of this study was to compare women with GDM 1995-99 against
      women with GDM 2012-13 regarding eventual differences in demographics and
      pregnancy outcome. STUDY DESIGN: In our region in Sweden, all pregnant women are
      tested for GDM with a 2-h 75g oral glucose tolerance test and the 2-h cut off
      value for GDM is >=10.0mmol/l in capillary plasma glucose. 1995-99 there were 131
      women with GDM and their medical journals were compared against the 210 women
      with GDM during 2012-13. The same screening and diagnostic method was uses during
      the whole time period. RESULTS: In the 2012-13 GDM pregnancies there were more
      non-Scandinavian women, more women with insulin treatment during pregnancy and a
      higher frequency of cesarean deliveries compared to 1995. First weight of the
      women during GDM pregnancy 2012-13 was significantly higher than the weight of
      women with GDM 1995-99, 71kg (43-138; n=201) and 65kg (43-133; n=125) (p=0.008)
      respectively. However, there was no significant difference in weight of the
      mother at delivery. Birth weight of the child in GDM pregnancies 1995-99 was
      3722.4g+/-578.2 (n=109; p=0.009), and in GDM pregnancies 2012-13 3555.6g+/-465.8
      (n=162). CONCLUSION: Even though women with GDM 2012-13 weigh more when they
      start the pregnancy there is no difference in weight at delivery compared to
      women with GDM 1995-99. This is also reflected on the newborn, that 2012-13 had
      significantly lower birth weight but with the same gestational length as 1995
      1999. We believe that this is due to a more active and intense treatment of women
      with GDM during pregnancy together with higher frequency of cesarean delivery.
      Prevention of large infants is crucial to avoid complications during delivery.

PMID- 26295791
TI  - Argon plasma coagulation is effective for prevention of recurrent esophageal
      varices after endoscopic injection sclerotherapy: Single-center case-control
      study.
AB  - BACKGROUND AND AIM: Esophageal varices are usually treated with endoscopic
      injection sclerotherapy (EIS) or endoscopic band ligation (EBL). However,
      frequent recurrences of varices after those procedures have been problematic.
      Argon plasma coagulation (APC) after EIS may be effective for preventing varix
      recurrence and, in recent years, we have routinely carried out APC after EIS. The
      aim of the present study was to verify the effectiveness of APC for preventing
      recurrence of varices after EIS. METHODS: A case-control study was carried out
      using a historical control cohort in a single center. The varix recurrence rate
      in 62 patients (34 men and 28 women, median age; 69 years) who underwent APC
      after EIS for hemorrhagic or risky esophageal varices (APC group) was compared
      with that of control patients who did not undergo APC after EIS (control group).
      Age-, sex-, and liver function-matched two control subjects were selected for one
      case subject (control group). Recurrence of varices was defined as rupture of
      varices or reappearance of risky varices. RESULTS: The 1-year and 2-year
      recurrence rates of the APC group were 9.7% and 11.3%, respectively. In contrast,
      the rates of the control group were 29.0% and 34.7%, respectively. Kaplan-Meier
      curves showed a significantly lower recurrence rate in the APC group (P = 0.013,
      log-rank test). No APC-related severe adverse events were observed. CONCLUSION:
      APC after EIS was safe and could significantly prevent recurrence of esophageal
      varices. Therefore, the addition of APC should be routinely carried out after
      EIS.

PMID- 26295792
TI  - High-resolution protein-protein docking by global optimization: recent advances
      and future challenges.
AB  - A computational protein-protein docking method that predicts atomic details of
      protein-protein interactions from protein monomer structures is an invaluable
      tool for understanding the molecular mechanisms of protein interactions and for
      designing molecules that control such interactions. Compared to low-resolution
      docking, high-resolution docking explores the conformational space in atomic
      resolution to provide predictions with atomic details. This allows for
      applications to more challenging docking problems that involve conformational
      changes induced by binding. Recently, high-resolution methods have become more
      promising as additional information such as global shapes or residue contacts are
      now available from experiments or sequence/structure data. In this review
      article, we highlight developments in high-resolution docking made during the
      last decade, specifically regarding global optimization methods employed by the
      docking methods. We also discuss two major challenges in high-resolution docking:
      prediction of backbone flexibility and water-mediated interactions. 

PMID- 26295793
TI  - Essential Oils from the Medicinal Herbs Upregulate Dopamine Transporter in Rat
      Pheochromocytoma Cells.
AB  - The dopamine transporter (DAT) protein, a component of the dopamine system,
      undergoes adaptive neurobiological changes from drug abuse. Prevention of relapse
      and reduction of withdrawal symptoms are still the major limitations in the
      current pharmacological treatments of drug addiction. The present study aimed to
      investigate the effects of essential oils extracted from Elsholtzia ciliata,
      Shinchim, Angelicae gigantis Radix, and Eugenia caryophyllata, well-known
      traditional Korean medicines for addiction, on the modulation of dopamine system
      in amphetamine-treated cells and to explore the possible mechanism underlying its
      therapeutic effect. The potential cytotoxic effect of essential oils was
      evaluated in PC12 rat pheochromocytoma cells using cell viability assays.
      Quantification of DAT, p-CREB, p-MAPK, and p-Akt was done by immunoblotting. DAT
      was significantly reduced in cells treated with 50 MUM of amphetamine in a time
      dependent manner. No significant toxicity of essential oils from Elsholtzia
      ciliata and Shinchim was observed at doses of 10, 25, and 50 MUg/mL. However,
      essential oils from A. gigantis Radix at a dose of 100 MUg/mL and E.
      caryophyllata at doses of 50 and 100 MUg/mL showed cytotoxicity. Treatment with
      GBR 12909, a highly selective DAT inhibitor, significantly increased DAT
      expression compared with that of amphetamine only by enhancing phosphorylation of
      mitogen-activated protein kinases (MAPK) and Akt. In addition, essential oils
      effectively induced hyperphosphorylation of cyclic-AMP response element-binding
      protein (CREB), MAPK, and Akt, which resulted in DAT upregulation. Our study
      implies that the essential oils may rehabilitate brain dopamine function through
      increased DAT availability in abstinent former drug users.

PMID- 26295794
TI  - Joint frailty models for zero-inflated recurrent events in the presence of a
      terminal event.
AB  - Recurrent event data arise frequently in longitudinal medical studies. In many
      situations, there are a large portion of subjects without any recurrent events,
      manifesting the "zero-inflated" nature of the data. Some of the zero events may
      be "structural zeros" as patients are unsusceptible to recurrent events, while
      others are "random zeros" due to censoring before any recurrent events. On the
      other hand, there often exists a terminal event which may be correlated with the
      recurrent events. In this article, we propose two joint frailty models for zero
      inflated recurrent events in the presence of a terminal event, combining a
      logistic model for "structural zero" status (Yes/No) and a joint frailty
      proportional hazards model for recurrent and terminal event times. The models can
      be fitted conveniently in SAS Proc NLMIXED. We apply the methods to model
      recurrent opportunistic diseases in the presence of death in an AIDS study, and
      tumor recurrences and a terminal event in a sarcoma study. 

PMID- 26295796
TI  - Reduced Susceptibility to Cefepime in Clinical Isolates of Enterobacteriaceae
      Producing OXA-1 Beta-Lactamase.
AB  - An increase of Enterobacteriaceae isolates with reduced susceptibility to
      cefepime (FEP) and amoxicillin/clavulanate (AMC) has been observed in our area.
      The aim of this study was to characterize this antibiotic resistance phenotype
      and its molecular epidemiology. A total of 33 Enterobacteriaceae strains were
      studied. blaOXA-1 genes and their genetic environment were analyzed by polymerase
      chain reaction (PCR) and sequencing. Plasmids were transferred by conjugation
      and/or transformation and classified using PCR-based inc/rep typing and IncF
      subtyping. Escherichia coli isolates were typed by phylogroup, pulsed-field gel
      electrophoresis (PFGE) and multilocus sequence typing. Outer membrane proteins
      were studied by sodium dodecylsulfate-polyacrylamide gel electrophoresis and
      expression of blaOXA-1 genes by reverse transcription-PCR. FEP minimum inhibitory
      concentration yielded values of 1-16 mg/L. Twenty-nine (87.9%) isolates produced
      OXA-1, of which 24 (82.7%) were located in class 1 integron, and 9 (27.3%)
      produced TEM-1. Among the 24 E. coli OXA-1-producers, PFGE revealed two main
      clusters: one belonged to C-ST88 and the other to B23-ST131. Thirteen plasmids
      containing blaOXA-1 were transferred, nine belonged to IncF replicon (4 F2:A1:B-,
      2 F1:A1:B1, 1 F1:A2:B-, 1 F18:A2:B1, 1 F5:A-:B1) and four were nontypeable. In
      conclusion, reduced susceptibility to FEP was mostly due to OXA-1 beta-lactamase.
      In E. coli, this increase is mainly due to the dissemination of two clones, which
      have captured different IncF plasmids. Among non-E. coli strains, five isolates
      produced OXA-1 and one isolate produced only TEM-1. 

PMID- 26295797
TI  - Direct renin inhibition with aliskiren improves ischemia-induced
      neovascularization: blood pressure-independent effect.
AB  - BACKGROUND: Renin is the rate limiting step for the activation of the renin
      angiotensin-aldosterone system, which is linked to the development of endothelial
      dysfunction, hypertension and atherosclerosis. However, the specific role of
      renin during physiological responses to tissue ischemia is currently unknown.
      Aliskiren is the only direct renin inhibitor that is clinically used as an orally
      active antihypertensive drug. Here we tested the hypothesis that aliskiren might
      improve neovascularization in response to ischemia. METHODS AND RESULTS: At a
      dose that did not modulate blood pressure (10 mg/kg), aliskiren led to improved
      blood flow recovery after hindlimb ischemia in C57BL/6 mice (Doppler flow ratios
      0.71 +/- 0.07 vs. 0.55 +/- 0.03; P < 0.05). In ischemic muscles, treatment with
      aliskiren was associated with a significant increase of vascular density, reduced
      oxidative stress levels and increased expression of VEGF and eNOS. Aliskiren
      treatment also significantly increased the number of bone marrow-derived
      endothelial progenitor cells (EPCs) after hindlimb ischemia. Moreover, the
      angiogenic properties of EPCs (migration, adhesion, integration into tubules)
      were significantly improved in mice treated with aliskiren. In vitro, aliskiren
      improves cellular migration and tubule formation in HUVECs. This is associated
      with an increased expression of nitric oxide (NO), and a significant reduction of
      oxidative stress levels. Importantly, the angiogenic properties of aliskiren in
      vitro and in vivo are completely abolished following treatment with the NOS
      inhibitor l-NAME. CONCLUSION: Direct renin inhibition with aliskiren leads to
      improved ischemia-induced neovascularization that is not dependant on blood
      pressure lowering. The mechanism involves beneficial effects of aliskiren on
      oxidative stress and NO angiogenic pathway, together with an increase in the
      number and the functional activities of EPCs.

PMID- 26295798
TI  - Cardio-ankle vascular index predicts for the incidence of cardiovascular events
      in obese patients: a multicenter prospective cohort study (Japan Obesity and
      Metabolic Syndrome Study: JOMS).
AB  - OBJECTIVE: The cardio-ankle vascular index (CAVI) is an index of arterial
      stiffness less dependent on blood pressure and an indicator suitable for
      assessing the arterial dysfunction. However, it remains unclear whether CAVI can
      predict the outcome of cardiovascular diseases (CVD) in obese patients. METHODS:
      A total of 425 obese Japanese outpatients (189 men and 236 women, mean age: 51.5
      years) were enrolled in a multicenter prospective cohort Japan, the Japan Obesity
      and Metabolic Syndrome Study (JOMS). Primary analysis regarding measurements of
      cardiovascular risk factors including CAVI and the occurrence of macrovascular
      complications was based on following the participants over a 5-year period.
      RESULTS: Of the eligible patients, 300 (78%) were followed into the fifth year.
      During the study period, 15 coronary heart disease, 7 stroke, and 6
      arteriosclerosis obliterans events occurred. All events occurred in 28 patients,
      and CVD incidence rate was 15.8 per 1000 person-years. In the analysis of
      adjusted models for traditional risk factors, CAVI was a significant factor for
      the incidence of events. In addition, high CAVI and low HDL-cholesterol were
      significant factors for the incidence of events in Cox stepwise multivariate
      analysis when age- and sex-adjusted (CAVI [per 1]: HR = 1.44 [1.02-2.02], p =
      0.037; HDL-cholesterol [per 1 mmol/L]: HR = 0.20 [0.06-0.69], p = 0.011). In
      addition, CAVI added value to atherosclerotic cardiovascular disease risk score
      in predicting the development of CVD. CONCLUSION: This study demonstrates for the
      first time that CAVI is an effective predictor of CVD events in obese patients.

PMID- 26295800
TI  - Evaluating Autologous Lipofilling for Parry-Romberg Syndrome-Associated Defects:
      A Systematic Literature Review and Case Report.
AB  - BACKGROUND: Parry-Romberg syndrome (PRS) is a rare craniofacial disease that
      causes progressive hemifacial atrophy of the soft tissue before spontaneously
      entering remission. Autologous fat grafting may provide a less invasive
      alternative, producing aesthetically pleasing results while avoiding the need for
      traditional microsurgical free flap coverage. METHODS: A systematic review of the
      literature was conducted. Inclusion and exclusion criteria were applied. The case
      report highlights the technique using two-dimensional and three-dimensional
      photography. RESULTS: Our review yielded 31 articles in addition to our case
      describing 147 cases of lipofilling to correct PRS soft-tissue defects. Patients
      underwent an average of 2.2 procedures, receiving on average 95 mL of grafted
      fat. Disease severity was classified into mild (41%), moderate (42%), and severe
      (17%) in the identified patients. Increasing disease severity correlated with an
      increasing number of procedures and fat-grafting volumes to achieve adequate
      aesthetic outcomes (mean, 1.5 and 38 mL; 2.3 and 81 mL; 3.7 and 129 mL,
      respectively). Reported benefits over flap-based reconstructions included
      reductions in cost (40%), operative time (50%), donor-site morbidity (52%), and
      rate of complications (33%). Aesthetic benefits cited included improved skin
      quality (65%), more natural contours (1%), and more natural facial expressions
      (10%). CONCLUSION: Fat grafting for correction of PRS-associated soft-tissue
      defects is receiving heightened acceptance for its ability to restore natural
      facial contours. While additional fat-grafting procedures may be required with
      increased disease severity, autologous fat grafting may be a beneficial option as
      a sole modality to correct PRS-associated soft-tissue atrophy.

PMID- 26295801
TI  - Data-Driven Information Extraction from Chinese Electronic Medical Records.
AB  - OBJECTIVE: This study aims to propose a data-driven framework that takes
      unstructured free text narratives in Chinese Electronic Medical Records (EMRs) as
      input and converts them into structured time-event-description triples, where the
      description is either an elaboration or an outcome of the medical event.
      MATERIALS AND METHODS: Our framework uses a hybrid approach. It consists of
      constructing cross-domain core medical lexica, an unsupervised, iterative
      algorithm to accrue more accurate terms into the lexica, rules to address Chinese
      writing conventions and temporal descriptors, and a Support Vector Machine (SVM)
      algorithm that innovatively utilizes Normalized Google Distance (NGD) to estimate
      the correlation between medical events and their descriptions. RESULTS: The
      effectiveness of the framework was demonstrated with a dataset of 24,817 de
      identified Chinese EMRs. The cross-domain medical lexica were capable of
      recognizing terms with an F1-score of 0.896. 98.5% of recorded medical events
      were linked to temporal descriptors. The NGD SVM description-event matching
      achieved an F1-score of 0.874. The end-to-end time-event-description extraction
      of our framework achieved an F1-score of 0.846. DISCUSSION: In terms of named
      entity recognition, the proposed framework outperforms state-of-the-art
      supervised learning algorithms (F1-score: 0.896 vs. 0.886). In event-description
      association, the NGD SVM is superior to SVM using only local context and semantic
      features (F1-score: 0.874 vs. 0.838). CONCLUSIONS: The framework is data-driven,
      weakly supervised, and robust against the variations and noises that tend to
      occur in a large corpus. It addresses Chinese medical writing conventions and
      variations in writing styles through patterns used for discovering new terms and
      rules for updating the lexica.

PMID- 26295802
TI  - Using BD Vacutainer CD4 Stabilization Tubes for Absolute Cluster of
      Differentiation Type 4 Cell Count Measurement on BD FacsCount and Partec Cyflow
      Cytometers: A Method Comparison Study from Zimbabwe.
AB  - BACKGROUND: Blood collected in conventional EDTA tubes requires laboratory
      analysis within 48 hours to provide valid CD4 cell count results. This restricts
      access to HIV care for patients from rural areas in resource-constraint settings
      due to sample transportation problems. Stabilization Tubes with extended storage
      duration have been developed but not yet evaluated comprehensively. OBJECTIVE: To
      investigate stability of absolute CD4 cell count measurement of samples in BD
      Vacutainer CD4 Stabilization Tubes over the course of 30 days. METHODS: This was
      a laboratory-based method comparison study conducted at a rural district hospital
      in Beitbridge, Zimbabwe. Whole peripheral blood from 88 HIV positive adults was
      drawn into BD Vacutainer CD4 Stabilization Tubes and re-tested 1, 2, 3, 5, 7, 14
      and 30 days after collection on BD FacsCount and Partec Cyflow cytometers in
      parallel. Absolute CD4 cell levels were compared to results from paired samples
      in EDTA tubes analysed on BD FacsCount at the day of sample collection
      (references methodology). Bland-Altman analysis based on ratios of the median CD4
      counts was used, with acceptable variation ranges for Limits of Agreements of +/
      20%. RESULTS: Differences in ratios of the medians remained below 10% until day
      21 on BD FacsCount and until day 5 on Partec Cyflow. Variations of Limits of
      Agreement were beyond 20% after day 1 on both cytometers. Specimen quality
      decreased steadily after day 5, with only 68% and 40% of samples yielding results
      on BD FacsCount and Partec Cyflow at day 21, respectively. CONCLUSIONS: We do not
      recommend the use of BD Vacutainer CD4 Stabilization Tubes for absolute CD4 cell
      count measurement on BD FacsCount or Partec Cyflow due to large variation of
      results and decay of specimen quality. Alternative technologies for enhanced CD4
      testing in settings with limited laboratory and sample transportation capacity
      still need to be developed.

PMID- 26295803
TI  - Association between Ocular Sensory Dominance and Refractive Error Asymmetry.
AB  - PURPOSE: To investigate the association between ocular sensory dominance and
      interocular refractive error difference (IRED). METHODS: A total of 219 subjects
      were recruited. The refractive errors were determined by objective refraction
      with a fixation target located 6 meters away. 176 subjects were myopic, with 83
      being anisometropic (IRED >= 0.75 D). 43 subjects were hyperopic, with 22 being
      anisometropic. Sensory dominance was measured with a continuous flashing
      technique with the tested eye viewing a Gabor increasing in contrast and the
      fellow eye viewing a Mondrian noise decreasing in contrast. The log ratio of
      Mondrian to Gabor's contrasts was recorded when a subject just detected the
      tilting direction of the Gabor during each trial. T-test was used to compare the
      50 values collected from each eye, and the t-value was used as a subject's ocular
      dominance index (ODI) to quantify the degree of ocular dominance. A subject with
      ODI >= 2 (p < 0.05) had clear dominance and the eye with larger mean ratio was
      the dominant one. Otherwise, a subject had an unclear dominance. RESULTS: The
      anisometropic subjects had stronger ocular dominance in comparison to non
      anisometropic subjects (rank-sum test, p < 0.01 for both myopic and hyperopic
      subjects). In anisometropic subjects with clear dominance, the amplitude of the
      anisometropia was correlated with ODI values (R = 0.42, p < 0.01 in myopic
      anisometropic subjects; R = 0.62, p < 0.01 in hyperopic anisometropic subjects).
      Moreover, the dominant eyes were more myopic in myopic anisometropic subjects
      (sign-test, p < 0.05) and less hyperopic in hyperopic anisometropic subjects
      (sign-test, p < 0.05). CONCLUSION: The degree of ocular sensory dominance is
      associated with interocular refractive error difference.

PMID- 26295804
TI  - NaHS Protects Cochlear Hair Cells from Gentamicin-Induced Ototoxicity by
      Inhibiting the Mitochondrial Apoptosis Pathway.
AB  - Aminoglycoside antibiotics such as gentamicin could cause ototoxicity in
      mammalians, by inducing oxidative stress and apoptosis in sensory hair cells of
      the cochlea. Sodium hydrosulfide (NaHS) is reported to alleviate oxidative stress
      and apoptosis, but its role in protecting aminoglycoside-induced hearing loss is
      unclear. In this study, we investigated the anti-oxidant and anti-apoptosis
      effect of NaHS in in vitro cultured House Ear Institute-Organ of Corti 1 (HEI
      OC1) cells and isolated mouse cochlea. Results from cultured HEI-OC1 cells and
      cochlea consistently indicated that NaHS exhibited protective effects from
      gentamicin-induced ototoxicity, evident by maintained cell viability, hair cell
      number and cochlear morphology, reduced reactive oxygen species production and
      mitochondrial depolarization, as well as apoptosis activation of the intrinsic
      pathway. Moreover, in the isolated cochlear culture, NaHS was also demonstrated
      to protect the explant from gentamicin-induced mechanotransduction loss. Our
      study using multiple in vitro models revealed for the first time, the potential
      of NaHS as a therapeutic agent in protecting against aminoglycoside-induced
      hearing loss. 

PMID- 26295805
TI  - Mathematical Modeling of Hepatitis C Prevalence Reduction with Antiviral
      Treatment Scale-Up in Persons Who Inject Drugs in Metropolitan Chicago.
AB  - BACKGROUND/AIM: New direct-acting antivirals (DAAs) provide an opportunity to
      combat hepatitis C virus (HCV) infection in persons who inject drugs (PWID). Here
      we use a mathematical model to predict the impact of a DAA-treatment scale-up on
      HCV prevalence among PWID and the estimated cost in metropolitan Chicago.
      METHODS: To estimate the HCV antibody and HCV-RNA (chronic infection) prevalence
      among the metropolitan Chicago PWID population, we used empirical data from three
      large epidemiological studies. Cost of DAAs is assumed $50,000 per person.
      RESULTS: Approximately 32,000 PWID reside in metropolitan Chicago with an
      estimated HCV-RNA prevalence of 47% or 15,040 cases. Approximately 22,000 PWID
      (69% of the total PWID population) attend harm reduction (HR) programs, such as
      syringe exchange programs, and have an estimated HCV-RNA prevalence of 30%. There
      are about 11,000 young PWID (<30 years old) with an estimated HCV-RNA prevalence
      of 10% (PWID in these two subpopulations overlap). The model suggests that the
      following treatment scale-up is needed to reduce the baseline HCV-RNA prevalence
      by one-half over 10 years of treatment [cost per year, min-max in millions]: 35
      per 1,000 [$50-$77] in the overall PWID population, 19 per 1,000 [$20-$26] for
      persons in HR programs, and 5 per 1,000 [$3-$4] for young PWID. CONCLUSIONS:
      Treatment scale-up could dramatically reduce the prevalence of chronic HCV
      infection among PWID in Chicago, who are the main reservoir for on-going HCV
      transmission. Focusing treatment on PWID attending HR programs and/or young PWID
      could have a significant impact on HCV prevalence in these subpopulations at an
      attainable cost.

PMID- 26295806
TI  - Impact of Childhood Adversity and Vasopressin receptor 1a Variation on Social
      Interaction in Adulthood: A Cross-Sectional Study.
AB  - BACKGROUND: Arginine vasopressin (AVP) plays a role in social behavior, through
      receptor AVPR1A. The promoter polymorphism AVPR1A RS3 has been associated with
      human social behaviors, and with acute response to stress. Here, the
      relationships between AVPR1A RS3, early-life stressors, and social interaction in
      adulthood were explored. METHODS: Adult individuals from a Swedish population
      based cohort (n = 1871) were assessed for self-reported availability of social
      integration and social attachment and for experience of childhood adversities.
      Their DNA samples were genotyped for the microsatellite AVPR1A RS3. RESULTS:
      Among males, particularly those homozygous for the long alleles of AVPR1A RS3
      were vulnerable to childhood adversity for their social attachment in adulthood.
      A similar vulnerability to childhood adversity among long allele carriers was
      found on adulthood social integration, but here both males and females were
      influenced. LIMITATION: Data were self-reported and childhood adversity data were
      retrospective. CONCLUSIONS: Early-life stress influenced the relationship between
      AVPR1A genetic variants and social interaction. For social attachment, AVPR1A was
      of importance in males only. The findings add to previous reports on higher acute
      vulnerability to stress in persons with long AVPR1A RS3 alleles and increased AVP
      levels.

PMID- 26295808
TI  - Statistical Properties Demand as Much Attention as Object Features.
AB  - Recent studies have argued that the statistical properties of a set of visual
      items can be extracted with little or even no cost. In the present study,
      observers (N = 188) performed a color task and an orientation task, and the
      attention effect was measured as the advantage of pre-cueing one of the two
      tasks. The color and orientation tasks required participants to report either an
      object feature or the mean of a 4*4 array (i.e., statistical property). The pre
      cueing advantages were approximately equal regardless of the nature of the tasks
      (object features vs. statistical properties), providing evidence that statistical
      properties are not perceived with zero cost, but demand as much attention as
      object features. 

PMID- 26295807
TI  - Using Low Levels of Stochastic Vestibular Stimulation to Improve Balance
      Function.
AB  - Low-level stochastic vestibular stimulation (SVS) has been associated with
      improved postural responses in the medio-lateral (ML) direction, but its effect
      in improving balance function in both the ML and anterior-posterior (AP)
      directions has not been studied. In this series of studies, the efficacy of
      applying low amplitude SVS in 0-30 Hz range between the mastoids in the ML
      direction on improving cross-planar balance function was investigated. Forty-five
      (45) subjects stood on a compliant surface with their eyes closed and were
      instructed to maintain a stable upright stance. Measures of stability of the
      head, trunk, and whole body were quantified in ML, AP and combined APML
      directions. Results show that binaural bipolar SVS given in the ML direction
      significantly improved balance performance with the peak of optimal stimulus
      amplitude predominantly in the range of 100-500 MUA for all the three directions,
      exhibiting stochastic resonance (SR) phenomenon. Objective perceptual and body
      motion thresholds as estimates of internal noise while subjects sat on a chair
      with their eyes closed and were given 1 Hz bipolar binaural sinusoidal electrical
      stimuli were also measured. In general, there was no significant difference
      between estimates of perceptual and body motion thresholds. The average optimal
      SVS amplitude that improved balance performance (peak SVS amplitude normalized to
      perceptual threshold) was estimated to be 46% in ML, 53% in AP, and 50% in APML
      directions. A miniature patch-type SVS device may be useful to improve balance
      function in people with disabilities due to aging, Parkinson's disease or in
      astronauts returning from long-duration space flight. 

PMID- 26295811
TI  - Nanoparticles: A Neurotoxicological Perspective.
AB  - The delivery of drugs to brain is a daunting task due to the presence of multiple
      protective barriers. Nanoparticles (NPs), due to their ability to deliver and
      accumulate drugs in brain by crossing the blood brain barrier, have emerged as
      effective brain targeting drug delivery system. The major drawback of NPs
      obstructing their application in brain related diseases is neurotoxicity which
      leads to memory deficit, behavioural changes, changes in the structure and
      membrane potential of the neurons. An understanding of the molecular mechanisms
      associated with nanoparticle induced neurotoxicity is essential to solve the
      problem. NPs induce cytotoxicity, genotoxicity and epigenetic changes. This
      review focuses on nanoparticles, their physicochemical characteristics,
      manifestations of neurotoxicity and the mechanisms through which neurotoxicity is
      induced. This review may help in improving the understanding of the mechanisms
      associated with nanoparticle induced neurotoxicity so as to devise ways to
      overcome the associated neurotoxicity. 

PMID- 26295809
TI  - Endothelial Cell mTOR Complex-2 Regulates Sprouting Angiogenesis.
AB  - Tumor neovascularization is targeted by inhibition of vascular endothelial growth
      factor (VEGF) or the receptor to prevent tumor growth, but drug resistance to
      angiogenesis inhibition limits clinical efficacy. Inhibition of the
      phosphoinositide 3 kinase pathway intermediate, mammalian target of rapamycin
      (mTOR), also inhibits tumor growth and may prevent escape from VEGF receptor
      inhibitors. mTOR is assembled into two separate multi-molecular complexes, mTORC1
      and mTORC2. The direct effect of mTORC2 inhibition on the endothelium and tumor
      angiogenesis is poorly defined. We used pharmacological inhibitors and RNA
      interference to determine the function of mTORC2 versus Akt1 and mTORC1 in human
      endothelial cells (EC). Angiogenic sprouting, EC migration, cytoskeleton re
      organization, and signaling events regulating matrix adhesion were studied.
      Sustained inactivation of mTORC1 activity up-regulated mTORC2-dependent Akt1
      activation. In turn, ECs exposed to mTORC1-inhibition were resistant to apoptosis
      and hyper-responsive to renal cell carcinoma (RCC)-stimulated angiogenesis after
      relief of the inhibition. Conversely, mTORC1/2 dual inhibition or selective
      mTORC2 inactivation inhibited angiogenesis in response to RCC cells and VEGF.
      mTORC2-inactivation decreased EC migration more than Akt1- or mTORC1
      inactivation. Mechanistically, mTORC2 inactivation robustly suppressed VEGF
      stimulated EC actin polymerization, and inhibited focal adhesion formation and
      activation of focal adhesion kinase, independent of Akt1. Endothelial mTORC2
      regulates angiogenesis, in part by regulation of EC focal adhesion kinase
      activity, matrix adhesion, and cytoskeletal remodeling, independent of
      Akt/mTORC1. 

PMID- 26295812
TI  - Experimental Brain Ischemic Preconditioning: A Concept to Putative Targets.
AB  - Neurodegeneration is the progressive loss of central neurons which may instigate
      many disabling psychological and neurological disorders like Alzheimer's disease,
      schizophrenia, parkinson's disease, prion's disease, and Huntington's disease. It
      has become imperative to address the need to discover novel molecular targets and
      therapeutic strategies to combat neurodegeneration. It is more essential to do
      so, because most of the accessible treatment focuses on correcting the symptoms
      of such diseases rather than its underlying pathophysiology. In the present
      article, we sought to discuss plausible connections between brain ischemic
      preconditioning and protective measures against chemical neurotoxicity. Brain
      ischemic preconditioning is reported to be effective against stroke like
      conditions and is studied chiefly to identify culpable molecular targets.
      Similarly chemical stressors are reported to be effective in preconditioning
      neuronal cells against chemical neurotoxicity. Keeping the concept of cross
      tolerance in mind this article encompasses the putative targets of both chemical
      preconditioning and ischemic preconditioning in search for a suitable connection
      based on the published literature. The distinctive groups of targets are
      individually discussed and principal targets such as oncogene Akt, glycogen
      synthase kinase 3-beta and heat shock proteins are emphasised. Identification of
      these targets may help to develop sophisticated newer therapeutic strategies to
      cure neurodegenerative disorders. 

PMID- 26295810
TI  - Inhibiting the Recruitment of PLCgamma1 to Kaposi's Sarcoma Herpesvirus K15
      Protein Reduces the Invasiveness and Angiogenesis of Infected Endothelial Cells.
AB  - Kaposi's sarcoma (KS), caused by Kaposi's sarcoma herpesvirus (KSHV), is a highly
      vascularised tumour of endothelial origin. KSHV infected endothelial cells show
      increased invasiveness and angiogenesis. Here, we report that the KSHV K15
      protein, which we showed previously to contribute to KSHV-induced angiogenesis,
      is also involved in KSHV-mediated invasiveness in a PLCgamma1-dependent manner.
      We identified betaPIX, GIT1 and cdc42, downstream effectors of PLCgamma1 in cell
      migration, as K15 interacting partners and as contributors to KSHV-triggered
      invasiveness. We mapped the interaction between PLCgamma1, PLCgamma2 and their
      individual domains with two K15 alleles, P and M. We found that the PLCgamma2
      cSH2 domain, by binding to K15P, can be used as dominant negative inhibitor of
      the K15P-PLCgamma1 interaction, K15P-dependent PLCgamma1 phosphorylation, NFAT
      dependent promoter activation and the increased invasiveness and angiogenic
      properties of KSHV infected endothelial cells. We increased the binding of the
      PLCgamma2 cSH2 domain for K15P by substituting two amino acids, thereby creating
      an improved dominant negative inhibitor of the K15P-dependent PLCgamma1
      activation. Taken together, these results demonstrate a necessary role of K15 in
      the increased invasiveness and angiogenesis of KSHV infected endothelial cells
      and suggest the K15-PLCgamma1 interaction as a possible new target for inhibiting
      the angiogenic and invasive properties of KSHV. 

PMID- 26295813
TI  - The Beneficial Effect of Cape Gooseberry Juice on Carbon Tetrachloride- Induced
      Neuronal Damage.
AB  - OBJECTIVE: Cape gooseberry (Physalis peruviana L.) belongs to the Solanaceae
      family. Physalis has many medicinal properties however, the beneficial effect of
      physalis in protecting against neurotoxins has not yet been evaluated. This
      experimental study investigated the protective effect of physalis juice against
      the oxidative damage induced by carbon tetrachloride (CCl4) in the rat brain.
      METHODS: The degrees of protection by physalis in brain tissues were evaluated by
      determining the brain levels of lipid peroxidation, nitric oxide, glutathione
      content and antioxidant enzyme activities (superoxide dismutase, catalase,
      glutathione-S-transferase, glutathione peroxidase and glutathione reductase),
      after CCl4) induction in the presence or absence of physalis. Adult male albino
      Wistar rats were divided into 4 groups, Group I served as the control group,
      Group II was intraperitoneally treated with 2 ml CCl4)/kg bwt for 12 weeks, Group
      III was supplemented with physalis juice via the drinking water for 12 weeks,
      Group IV was supplemented with physalis juice and was intraperitoneally injected
      weekly with CCl4). RESULTS: Treatment with CCl4) was significantly associated
      with a disturbance in the oxidative status in the brain tissues; this was marked
      by a significant (p<0.05) elevation in the lipid peroxidation and nitric oxide
      levels with a concomitant reduction in glutathione content compared to the
      control, along with a remarkable reduction in antioxidant enzymes. The
      administration of physalis along with CCl4) juice significantly (p<0.05)
      alleviated the changes in enzymatic antioxidant activity when compared to the
      CCl4) treated group. Furthermore, physalis juice supplemention inhibited
      apoptosis, as indicated by the increase of Bcl-2 immunoreactivity in brain
      tissue. CONCLUSION: Our results suggest that physalis juice could be effective in
      preventing neurotoxicity and the neuroprotective effect of physalis might be
      mediated via antioxidant and anti-apoptosis activities.

PMID- 26295814
TI  - Neuroprotective Effects of the Securinine-Analogues: Identification of
      Allomargaritarine as a Lead Compound.
AB  - Oxidative stress and mitochondrial disturbances are the common and important
      causative factors of aging, and play an important role in the late onset of
      sporadic neurodegenerative diseases, including Alzheimer disease (AD).
      Furthermore, emerging evidence from in vitro and in vivo disease models suggests
      that oxidative stress and increased vulnerability to induction of mitochondrial
      permeability transition leads to the pathogenesis of the neurological disorders.
      Towards the goals of developing effective neuroprotectors, this article describes
      the synthesis and neuroprotective studies of various derivatives of the naturally
      occurring alkaloid securinine, based on which a lead compound, allomargaritarine
      (a diastereomer of margaritarine), was identified as an effective therapeutic for
      neuroprotection. Allomargaritarine exhibits high antioxidant activity, and has
      significant mitoprotective effect on cellular models of neurodegeneration. 

PMID- 26295816
TI  - Chronic Migraineurs Form Carboxyhemefibrinogen and Iron-Bound Fibrinogen.
AB  - Chronic migraine (CM) is a disabling painful condition that is associated with
      dementia and thrombotic disease. It has been proposed that carbon monoxide (CO)
      and iron may play a role in CM, and CO and iron are products of the heme
      oxygenase system which is widespread within the brain. Further, CO and iron
      enhance plasmatic coagulation in part via a fibrinogen-dependent mechanism. Thus,
      our goal was to determine whether patients with CM had experienced
      carboxyhemefibrinogen formation, iron bound fibrinogen formation and plasmatic
      hypercoagulability. Nonsmokers with CM were recruited after informed, written
      consent. Blood was collected, anticoagulated with sodium citrate, and then
      centrifuged with plasma stored at -80oC. Carboxyhemefibrinogen formation, iron
      bound fibrinogen formation and coagulation kinetics were determined via
      thrombelastographic methods. Patient results were compared with laboratory values
      generated from normal control plasmas. Incidence (95% confidence intervals) of
      the various parameters was determined using the Clopper-Pearson method. Twenty
      six CM patients (24 female) were recruited; they were 46+/-12 years old. With
      regard to fibrinogen modification, 88.5% (69.8%-97.6%) of CM patients had
      formation of carboxyhemefibrinogen, iron bound fibrinogen, or both. With regard
      to coagulation, 42.3% (23.4%-63.1%) of patients had abnormally decreased time to
      clot initiation, 80.8% (60.6%-93.4%) had abnormally large velocity of clot
      formation, and 46.2% (26.6%-66.7%) had abnormally strong clot strength. Patients
      with CM have a large incidence of carboxyhemefibrinogen and iron bound fibrinogen
      formation and hypercoagulability. Confirmatory and potential therapeutic clinical
      trials targeting CO and iron modified hypercoagulation as a source of pain and
      vascular disease in CM patients are indicated. 

PMID- 26295815
TI  - Application of Polymeric Nanoparticles for CNS Targeted Zinc Delivery In Vivo.
AB  - A dyshomeostasis of zinc ions has been reported for many psychiatric and
      neurodegenerative disorders including schizophrenia, attention deficit
      hyperactivity disorder, depression, autism, Parkinson's and Alzheimer's disease.
      Furthermore, alterations in zinc-levels have been associated with seizures and
      traumatic brain injury. Thus, altering zinclevels within the brain is emerging as
      a new target for the prevention and treatment of psychiatric and neurological
      diseases. However, given the restriction of zinc uptake into the brain by the
      blood-brain barrier, methods for controlled regulation and manipulation of zinc
      concentrations within the brain are rare. Here, we performed in vivo studies
      investigating the possibility of brain targeted zinc delivery using zinc-loaded
      nanoparticles which are able to cross the blood-brain barrier. After injecting
      these nanoparticles, we analyzed the regional and time-dependent distribution of
      zinc and nanoparticles within the brain. Moreover, we evaluated whether the
      presence of zinc-loaded nanoparticles alters the expression of zinc sensitive
      genes and proteins such as metallothioneins and zinc transporters and quantified
      possible toxic effects. Our results show that zinc loaded g7 nanoparticles offer
      a promising approach as a novel non - invasive method to selectively enrich zinc
      in the brain within a small amount of time. 

PMID- 26295817
TI  - A Fluorescence Resonance Energy Transfer Assay For Monitoring alpha- Synclein
      Aggregation in a Caenorhabditis Elegans Model For Parkinson's Disease.
AB  - The aggregation of alpha-synuclein (Syn or S) to form insoluble fibrils is
      important in the pathogenesis of Parkinson's disease, but key risk factors remain
      ill-defined. We have developed Fluorescence Resonance Energy Transfer (FRET)
      based assays for alpha-synuclein aggregation, using Green Fluorescent Protein
      variants Cerulean (C) or Venus (V), fused to each other (CV, VC) or to human
      synuclein (SC, SV etc). Bacterially expressed proteins were purified to
      homogeneity, and C-terminal fusions SC and SV largely retained their ability to
      aggregate in vitro. FRET signals from mixtures of SC and SV were used to monitor
      aggregation. These fusion genes were linked to the C. elegans unc-54 myosin
      promoter to generate integrated transgenic strains. Increased FRET signals,
      indicative of S aggregation, were observed following treatment of unc-54::SC +
      unc-54::SV double transgenic worms with low concentrations of mercury or
      chlorpyrifos, or with RNAi against hsp-70 and hip-1. Opposite changes in Yellow
      Fluorescent Protein (YFP) fluorescence in an unc-54::SV strain (NL5901) are
      likely to reflect FRET from Yellow Fluorescent Protein to aggregates of Syn
      fusion protein. This could provide the basis for a high throughput screening
      assay, which could be used for studying the effects of toxic chemicals and
      environmental pollutants on the aggregation of proteins such as Syn in vivo. 

PMID- 26295818
TI  - In Silico Analysis of Binding Interaction of Mamba Toxins with M4 and M2
      Muscarinic Acetylcholine Receptors for Therapeutic Use in Alzheimer's Disease.
AB  - Muscarinic acetylcholine receptors are stimulated by the neurotransmitter
      acetylcholine and are involved in various functions across the human body. These
      receptors have surfaced for their potential use as targets in treatment of
      Alzheimer's disease. Muscarinic receptors have been reported to show binding
      interaction with various mamba toxins, such as dendrotoxins and muscarinic toxins
      that act as antagonists of these receptors. Therefore, in our study we have
      focused on the binding analysis of these mamba toxins with the M4 and M2
      muscarinic acetylcholine autoreceptors for their potential use as targets in
      treating cognitive symptoms associated with Alzheimer's disease. A ligand dataset
      was developed that consisted of dendrotoxins and muscarinic toxins originating
      from various mamba species. Receptor dataset consisted of M4 and M2 muscarinic
      acetylcholine autoreceptors. Docking studies were performed using AutoDock 4.2
      between these ligands with each receptor and further analysis was done using
      various computational tools. Docking experiments were performed and analyzed to
      check the binding compatibilities between mamba toxins and muscarinic
      acetylcholine autoreceptors. Detail analysis revealed that these ligands bind to
      active site residues of both receptors. Therefore by these in silico results, we
      suggest that the mamba toxins can be potential antagonists of the M4 and M2
      muscarinic acetylcholine autoreceptors. 

PMID- 26295819
TI  - Development of a Novel and Robust Pharmacological Model of Okadaic Acid-induced
      Alzheimer's Disease in Zebrafish.
AB  - Alzheimer's disease (AD) is the leading neurodegenerative disorder affecting the
      world's elderly population. Most experimental models of AD are transgenic or
      pharmacological in nature, and do not simulate the entire pathophysiology. In the
      present study, we developed a pharmacologically induced AD using the zebrafish, a
      species that can recapitulate most of the phenotypes of the disease. The
      pharmacological agent being used, okadaic acid (OKA) has also been utilized to
      study AD in other species. In this model, the immunohistochemistry of
      phosphorylated glycogen synthase-3alpha/beta, Abeta, p-tau, tau protein, and
      senile plaque formation in zebrafish brain were all significantly increased with
      increasing exposure to OKA. These represent the majority of the histological
      hallmarks of AD pathophysiology. The observed changes were also accompanied by
      learning and memory deficits which are also important components in AD
      pathophysiology. Zebrafish disease models are gaining popularity mostly due to
      their economic cost and relevance to human disease pathophysiology. Current
      pharmacological methods of inducing AD in zebrafish are not adequately developed
      and do not represent all the features of the disease. OKA-induced AD in zebrafish
      can become a cost efficient model to study drug discovery for AD. It may also be
      used to unravel the molecular mechanisms underlying the complex pathophysiology
      that leads to AD using relatively economical species. 

PMID- 26295820
TI  - Commentary: Participation of Sox-1 Expression and Signaling of beta-Catenin in
      the Pathophysiology of Generalized Seizures in Cerebellum of Rat.
AB  - Epilepsy is one of the most common neurological disorders in humans, and the role
      of cerebellum in its physiopathology remains the subject of study. Bergmann glia
      in the cerebellar cortex regulates the homeostasis of Purkinje cells, the axons
      of which target the dentate and interpositus nuclei, which form the main
      cerebellar output to other structures in the central nervous system involved in
      Epilepsy. Sox-1 is a transcription factor expressed in Bergmann glia and its
      binding to beta-Catenin further inhibits the Wnt pathway. beta-Catenin is widely
      expressed in cerebellum. It has been reported that beta-Catenin signaling is
      increased as the hippocampus receives repeated electrical stimuli and this is
      related with apoptosis of neurons. In the cerebellum, the recurrence of seizures
      results in Purkinje cells death, although the mechanisms remain unclear. 

PMID- 26295821
TI  - Therapeutic Potential of Erythropoietin in Retinal and Optic Nerve Diseases.
AB  - Recent studies have shown that, in addition to its well-known erythropoietic
      effects, erythropoietin has anti-inflammatory, neuroprotective, and neurotrophic
      effects in different tissues including the retina and optic nerve. In this
      review, we made a comprehensive search to define the therapeutic potential of
      erythropoietin in retinal and optic nerve diseases that lead to blindness. 

PMID- 26295822
TI  - Jatrorrhizine Protects Against Okadaic Acid Induced Oxidative Toxicity Through
      Inhibiting the Mitogen-Activated Protein Kinases Pathways in HT22 Hippocampal
      Neurons.
AB  - Alzheimer's disease (AD) is a neurodegenerative disease characterized by deposit
      of amyloid plaques and neurofibrillary tangles and oxidative stress plays an
      essential role in the pathogenesis of AD. Jatrorrhizine (JAT), a Coptidis
      Rhizome, has multiple biological functions such as anti-oxidation and anti
      inflammation. Herein, we investigated the neuroprotective effects of JAT on
      okadaic acid (OA)- induced cytotoxicity and apoptosis in HT22 cells. Following
      the exposure to 80 nmol/L OA for 12h, the reduction in cell survival, activities
      of superoxide dismutase, glutathione peroxidase and mitochondria membrane
      potential has been shown in HT22 cells. In contrast, OA increased levels of
      lactate dehydrogenase, malondialdehyde production and intracellular reactive
      oxygen species. OA also enhanced the expression of Bax but decreased the levels
      of Bcl-2, OA also upregulated the expression of cleaved caspase-3, phosphorylated
      extracellular signal-regulated kinases 1/2, phosphorylated c-Jun N-terminal
      kinases, phosphorylated p38 and NF-kappa B p65 subunit in HT22 cells and this up
      regulation was attenuated by JAT which was pre-incubated for 12h in the cells
      prior to OA exposure. In conclusion, our data present the protective role of JAT
      in OA induced cytotoxicity, via its antioxidant and anti-apoptotic properties by
      inhibiting the mitogen-activated protein kinases pathways in HT22 hippocampal
      neurons. These results indicate that JAT may be the potential target to treat AD
      induced by oxidative stress and apoptosis.

PMID- 26295823
TI  - GSTP1 Polymorphisms and their Association with Glutathione Transferase and
      Peroxidase Activities in Patients with Motor Neuron Disease.
AB  - Glutathione S-transferase pi (GSTP1) is a crucial enzyme in detoxification of
      electrophilic compounds and organic peroxides. Together with Se-dependent
      glutathione peroxidase (Se-GSHPx) it protects cells against oxidative stress
      which may be a primary factor implicated in motor neuron disease (MND)
      pathogenesis. We investigated GSTP1 polymorphisms and their relationship with GST
      and Se-GSTPx activities in a cohort of Polish patients with MND. Results were
      correlated with clinical phenotypes. The frequency of genetic variants for GSTP1
      exon 5 (I105V) and exon 6 (A114V) was studied in 104 patients and 100 healthy
      controls using real-time polymerase chain reaction. GST transferase activity was
      determined in serum with 1-chloro-2,4-dinitrobenzene, its peroxidase activity
      with cumene hydroperoxide, and Se-GSHPx activity with hydrogen peroxide. There
      were no differences in the prevalence of GSTP1 polymorphism I105V and A114V
      between MND and controls, however the occurrence of CT variant in codon 114 was
      associated with a higher risk for MND. GSTP1 polymorphisms were less frequent in
      classic ALS than in progressive bulbar palsy. In classic ALS C* (heterozygous I
      /V and A /V) all studied activities were significantly lower than in classic ALS
      A* (homozygous I /I and A/A). GST peroxidase activity and Se-GSHPx activity were
      lower in classic ALS C* than in control C*, but in classic ALS A* Se-GSHPx
      activity was significantly higher than in control A*. It can be concluded that
      the presence of GSTP1 A114V but not I105V variant increases the risk of MND, and
      combined GSTP1 polymorphisms in codon 105 and 114 may result in lower protection
      of MND patients against the toxicity of electrophilic compounds, organic and
      inorganic hydroperoxides. 

PMID- 26295824
TI  - A comprehensive review on the efficacy of S-Adenosyl-L-methionine in Major
      Depressive Disorder.
AB  - OBJECTIVE: To review the antidepressant efficacy of S-Adenosyl-L-Methionine
      (SAMe) both in monotherapy and/or in augmentation with antidepressants to better
      understand its potential role in the treatment of patients with Major Depressive
      Disorder (MDD) and Treatment-Resistant Depression (TRD). DATA SOURCES: A
      MEDLINE/PubMed search was carried out by using the following set of keywords:
      ((SAMe OR SAdenosyl- L-Methionine) AND (major depressive disorder OR
      depression)). Data Selection and Data Extraction: No language or time
      restrictions were placed on the electronic searches. Randomized controlled trials
      and open trials involving humans were here included and analyzed. The references
      of published articles identified in the initial search process were also examined
      for any additional studies appropriate for the review. DATA SYNTHESIS: SAMe is an
      important physiologic compound, playing a central role as precursor molecule in
      several biochemical reactions. Numerous studies have shown that SAMe may affect
      the regulation of various critical components of monoaminergic neurotransmission
      involved in the pathophysiology of MDD. Some findings have suggested its
      antidepressant efficacy in treating MDD. Several randomized controlled trials
      have supported that the antidepressant efficacy of SAMe in monotherapy is
      superior to placebo and tricyclic antidepressants. Recent findings have also
      demonstrated its efficacy in patients nonresponsive to selective serotonin
      reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. CONCLUSION:
      Overall, SAMe is a well-tolerated medication, which may offer considerable
      advantages as an alternative to antidepressant drugs or as an add-on therapy in
      the treatment of MDD and TRD. More large-scale controlled trials are needed to
      gain a better understanding of the relative efficacy of this drug.

PMID- 26295825
TI  - Relationship between chronic disturbance of 2,3-diphosphoglycerate metabolism in
      erythrocytes and Alzheimer disease.
AB  - Alzheimer disease (AD) is one of the most common neurodegenerative disorders
      widely occurring among the elderly. The pathogenic mechanisms involved in the
      development of this disease are still unknown. In AD, in addition to brain, a
      number of peripheral tissues and cells are affected, including erythrocytes. In
      this study, we analyzed glycolytic energy metabolism, antioxidant status,
      glutathione, adenylate and proteolytic systems in erythrocytes from patients with
      AD and compared with those from age-matched controls and young adult controls.
      Glycolytic enzymes hexokinase, phosphofructokinase, bisphosphoglycerate mutase
      and bisphosphoglycerate phosphatase displayed lower activities in agematched
      controls, and higher activities in AD patients, as compared to those in young
      adult control subjects. In both aging and AD, oxidative stress is increased in
      erythrocytes whereas elevated concentrations of hydrogen peroxide and organic
      hydroperoxides as well as decreased glutathione/glutathione disulfide ratio and
      glutathione transferase activity can be detected. These oxidative disturbances
      are also accompanied by reductions in ATP levels, adenine nucleotide pool size
      and adenylate energy charge. Caspase-3 and calpain activities in age-matched
      controls and AD patients were about three times those of young adult controls.
      2,3-diphosphoglycerate levels were significantly decreased in AD patients. Taken
      together these data suggest that AD patients are associated with chronic
      disturbance of 2,3-diphosphoglycerate metabolism in erythrocytes. These defects
      may play a central role in pathophysiological processes predisposing elderly
      subjects to dementia. 

PMID- 26295826
TI  - Ouabain-Induced Signaling and Cell Survival in SK-N-SH Neuroblastoma Cells
      Differentiated by Retinoic Acid.
AB  - Ouabain stimulates activation of various signaling cascades such as protein
      kinase B (Akt) and Extracellular-signaling-regulated kinase 1/2 (ERK 1/2) in
      various cell lines. Retinoic acid (RA) is commonly used to induce neuroblastoma
      differentiation in cultures. Upon RA administration, human neuroblastoma cell
      line, SK-N-SH demonstrated neurite extensions, which is an indicator of neuronal
      cell differentiation. Here we report that ouabain-induced signaling is altered
      under the action of 1 MUM RA in human neuroblastoma SK-N-SH cells. RA increased
      the expression of p110alpha subunit of phosphoinositide 3-kinase (PI3K), Akt and
      beta1 subunit of Na(+)/K(+)-ATPase. Ouabain activated Akt and ERK 1/2 in
      differentiated SK-N-SH cells; this effect was not observed in non-differentiated
      SK-N-SH cells. Long-term incubation of non-differentiated SK-N-SH with 1 MUM
      ouabain led to a decrease in the number of cells; this effect was reduced in
      differentiated SK-N-SH cells. Taken together, these results suggest that ouabain
      leads to cell death in neuroblastoma cells rather than neuronal cells due to the
      different response to ouabain manifested by activation of Akt and ERK 1/2.
      HIGHLIGHTS: * RA increases the expression of p110alpha subunit of PI3K, Akt and
      beta1 subunit of Na(+)/K(+)-ATPase * Ouabain induces activation of Akt and ERK
      1/2 in differentiated SK-N-SH cells but not in non-differentiated cells * 1 MUM
      ouabain leads to a decrease in the number of cells in non-differentiated SK-N-SH
      * Reduction of ouabain-induced cell death in differentiated SK-N-SH.

PMID- 26295827
TI  - The Association of Palmitoylethanolamide with Luteolin Decreases
      Neuroinflammation and Stimulates Autophagy in Parkinson's Disease Model.
AB  - Parkinson's disease (PD) is a disorder resulted by degeneration of dopaminergic
      neurons. To counteract the neuroinflammation and oxidative stress of PD, we
      decided to test a new composite constituted by palmitoylethanolamide (PEA) and
      luteolin (Lut), in a mass ratio of 10:1, respectively (co-ultraPEALut). In this
      study the neuroprotective property of the new compound was investigated. For the
      in vivo model of PD, mice received four injections of the dopaminergic neurotoxin
      1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP). Starting 24 h after the
      first administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), we
      treated animals with co-ultraPEALut daily until 7 days. On day 8, brains were
      processed for Western blotting and immunohistochemical analysis. Treatment with
      co-ultraPEALut reduced the specific markers of PD (tyrosine hydroxylase
      immunopositive), and the increased levels of activated astrocytes and pro
      inflammatory cytokines as well as inducible nitric oxide synthase. Further, the
      possible association of autophagy with the beneficial effects of coultraPEALut.
      Western blot analysis and immunofluorescence staining showed that co-ultraPEALut
      administration increased autophagy process. These data were confirmed by an in
      vitro model, using SH-SY5Y neuroblastoma cells. Western blot analysis showed that
      co-ultraPEALut pre-treatment maintained high Beclin-1 and p62 expression, while
      continued to inhibit the p70S6K expression. Altogether, these results put forward
      that treatment with co-ultraPEALut is able to modulate both the neuroinflammatory
      process and the autophagic pathway involved in PD, actions which may underlie its
      neuroprotective effect. 

PMID- 26295828
TI  - Nanoparticles as Alternative Strategies for Drug Delivery to the Alzheimer Brain:
      Electron Microscopy Ultrastructural Analysis.
AB  - One of the biggest problems and challenges for the development of new drugs and
      treatment strategies against Alzheimer Disease (AD) is the crossing of target
      drugs into the blood brain barrier. The use of nanoparticles in drug delivery
      therapy holds much promise in targeting remote tissues, and as a result many
      studies have attempted to study the ultrastructural localization of nanoparticles
      in various tissues. However, there are currently no in vivo studies demonstrating
      the ultrastructural distribution of nanoparticles in the brain. The aim of this
      study was to address how intraperitoneal injection of silver nanoparticles in the
      brain leads to leaking on the inter-endothelial contact and luminal plasma
      membrane, thus elucidating the possibility of penetrating into the most affected
      areas in the Alzheimer brain (vascular endothelium, perivascular, neuronal and
      glial cells). Our results show that the silver nanoparticles reached the brain
      and were found in hippocampal areas, indicating that they can be conjugated and
      used to deliver the drugs into the cell cytoplasm of the damaged brain cells. The
      present study can be useful for the development of novel drug delivering therapy
      and useful in understanding the delivery, distribution and effects of silver
      nanoparticles in AD brain tissue at cellular and subcellular level. 

PMID- 26295829
TI  - Tetrahydroxystilbene Glucoside Improves Neurotrophic Factors Release in Cultured
      Astroglia.
AB  - Tetrahydroxystilbene glucoside (TSG), one of the main ingredients of Polygonum
      multiflorum, has a great number of beneficial effects for health including anti
      oxidant, free radicalscavenging and anti-inflammatory properties. However, the
      potential effects of TSG on neurotrophic factors release remain unclear. In this
      study, rat primary astroglia cultures were applied to investigate TSG-mediated
      neurotrophic effects. The protein levels and production of glial cell-line
      derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF) and
      nerve growth factor (NGF) in astroglia and the culture medium were determined by
      western blotting assay and ELISA, respectively. Results indicated that TSG
      increased the production of neurotrophic factors in a concentration-dependent
      manner. At different time points of TSG treatment, the BDNF and NGF production in
      the culture medium was increased 48 h after treatment, while GDNF secretion was
      initially induced 24 h after TSG treatment. Consistent with the neurotrophic
      factors release, TSG significantly increased the BDNF, GDNF and NGF protein
      expressions in astroglia. Furthermore, TSG significantly induced the
      phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and a specific
      ERK inhibitor-U0126 inhibited TSG-mediated secretion of BDNF, GDNF and NGF.
      Overall, this study demonstrated that TSG induces astroglia-derived neurotrophic
      factors release, suggesting TSG might hold a therapeutic potential for
      neurological disorders. 

PMID- 26295830
TI  - PAX6 expression may be protective against dopaminergic cell loss in Parkinson's
      disease.
AB  - The transcription factor Pax6 is a well-accepted neurogenic determinant during
      development, in adult neural progenitor cells and in acute brain injury models.
      In the adult brain Pax6 is expressed in selective populations of dopaminergic
      neurons, and thus may have a role to play in Parkinson's disease (PD). This study
      looked at post-mortem tissue from patients with PD and in particular the
      substantia nigra which showed a reduced number of PAX6+ cells compared to age and
      sex matched control tissue. In an animal model of PD, there was an early
      transient increase in the number of SN Pax6+ cells at the time of cell loss
      through apoptosis. Finally we showed that an over-expression of Pax6 in SH-SY5Y
      cells treated with PD relevant neurotoxins, resulted in an increase in cell
      survival and a reduction in markers of apoptosis and oxidative stress. These
      results suggest that Pax6 may have a role to play in the loss of dopaminergic
      neurons in PD. 

PMID- 26295831
TI  - Novel Lactulose and Melibiose Targeting Autophagy to Reduce PolyQ Aggregation in
      Cell Models of Spinocerebellar Ataxia 3.
AB  - Trehalose, a chemical chaperone and mTOR-independent autophagy enhancer, has
      shown promise in models of Huntington's disease, Parkinson's disease and
      tauopathies. In this study, two trehalase analogs, lactulose and melibiose, were
      examined for their potentials in spinocerebellar ataxia treatment. Using a SCA3
      ATXN3/Q75-GFP cell model, we found that the ATXN3/Q75 aggregation was
      significantly prohibited by lactulose and melibiose because of their abilities to
      up-regulate autophagy. Meanwhile, lactulose and melibiose reduced reactive oxygen
      species production in ATXN3/Q75 cells. Both of them further inhibited the
      ATXN3/Q75 aggregation in neuronally differentiated SH-SY5Y cells. These findings
      suggest the therapeutic applications of novel trehalose analogs in polyglutamine
      aggregation-associated neurodegenerative diseases. 

PMID- 26295832
TI  - Recognition-driven assembly of self-limiting supramolecular protein nanoparticles
      displaying enzymatic activity.
AB  - We report the recognition-driven assembly of self-limiting protein nanoparticles
      displaying enzymatic activity. Solution self-assembly of concanavalin A lectin
      and glycoenzyme glucose oxidase leads to the spontaneous formation of biocolloids
      with well-defined dimensions, narrow size distribution and remarkable stability.
      These biocolloids successfully recognize a glycosylated modified electrode
      retaining the enzyme activity. 

PMID- 26295833
TI  - In Vitro Model of a Fibrosa Layer of a Heart Valve.
AB  - The fibrosa layer of a cardiac aortic valve is composed mostly of a dense network
      of type I collagen fibers oriented in circumferential direction. This main layer
      bears the tensile load and responds to the high stress on a leaflet. The inner
      fibrosa layer is also the site of pathophysiologic changes that result in
      valvular dysfunction, including stenosis and regurgitation. In vitro studies of
      these changes are limited by the absence of a substrate that mimics the
      circumferentially oriented structure of the fibrosa layer. In heart valve tissue
      engineering, generation of this layer is challenging. This study aimed to develop
      an artificial fibrosa layer of a native aortic leaflet. A unique morphologically
      biomimicked, pliable, but standalone substrate with circumferentially oriented
      nanofibers was fabricated by electrospinning on a novel collector designed for
      this study. The substrate had low-bulk tensile stiffness and ultimate strength;
      thus, cultured valvular interstitial cells (VICs) showed a fibroblast phenotype
      that is generally observed in a healthy aortic leaflet. Furthermore, gene and
      protein expression and morphology of VICs in substrates were close to those in
      the fibrosa layer of a native aortic leaflet. This artificial fibrosa layer can
      be useful for in vitro studies of valvular dysfunctions. 

PMID- 26295834
TI  - Remodeling Amyloid Fibers: Baker's Yeast Shows Us the Way.
AB  - Proteopathies are a large and diverse group of human diseases that are caused by
      protein misfolding. Well-known examples of proteopathies are Alzheimer's and
      Parkinson's disease, which are both linked to amyloid fibril formation. In this
      issue of Chemistry & Biology, Castellano et al. (2015) describe the way to
      harness the power of a protein from baker's yeast, Hsp104, to disaggregate the
      fibrils. 

PMID- 26295835
TI  - New Griselimycins for Treatment of Tuberculosis.
AB  - Griselimycin (GM), a natural product isolated a half century ago, is having a bit
      of a renaissance. After being known for more than 50 years, it is now being
      pursued as a treatment for tuberculosis. With the new mechanism of action,
      excellent in vitro and in vivo activity against sensitive and drug-resistant
      Mycobacterium tuberculosis, and the improved pharmacokinetic properties, the
      cyclohexyl derivative of GM demonstrates a high translational potential. 

PMID- 26295836
TI  - Epidemiological Characteristics of Hypertension in the Elderly in Beijing, China.
AB  - BACKGROUND/OBJECTIVES: The prevalence rate of hypertension increases
      significantly with the aging society, and hypertension is obviously becoming a
      major health care concern in China. The aim of the study was to explore the
      epidemiological characteristics of hypertension in the elderly and to provide a
      basis for the prevention of hypertension. DESIGN: 3-cross sectional studies in
      2000, 2004, and 2007, respectively. SETTING: Beijing, China. PARTICIPANTS: A
      group of 2,832, 1,828, and 2,277 elderly residents aged >=60 years were included
      this study in 2000, 2004, and 2007, respectively. INTERVENTION: None.
      MEASUREMENTS: Statistical sampling techniques included cluster, stratification,
      and random selection. Trained staff used a comprehensive geriatric assessment
      questionnaire and a standard survey instrument to complete the assessments.
      During the person-to-person interviews, the participants' demographic
      characteristics, living conditions, and health status were collected, and their
      blood pressure was measured. RESULTS: The prevalence rates (69.2%, 61.9%, and
      56.0%) of hypertension and the control rates (22.6%, 16.7%, and 21.5%) lowered
      annually, while the awareness rates (43.7%, 55.8%, and 57.6%) of the treatment
      elevated annually in 2000, 2004, and 2007, respectively. There was no increase in
      the control rates for males (26.2%, 16.7%, and 20.8%), younger participants
      (28.0%, 18.4%, and 21.0%), and rural residents (19.5%, 9.6%, and 13.4%) in 2000,
      2004, and 2007, respectively. CONCLUSIONS: Our study findings indicated that the
      prevalence of hypertension is high in rural elderly participants, while the rates
      of awareness, treatment, and control were low. This suggests that effective
      public measures need to be developed to improve the prevention and control of
      hypertension.

PMID- 26295837
TI  - Three-Year Improvements in Weight Status and Weight-Related Behaviors in Middle
      School Students: The Healthy Choices Study.
AB  - INTRODUCTION: Few dissemination evaluations exist to document the effectiveness
      of evidence-based childhood obesity interventions outside the research setting.
      OBJECTIVE: Evaluate Healthy Choices (HC), a multi-component obesity prevention
      program, by examining school-level changes in weight-related behaviors and weight
      status and the association of implementation components with odds of
      overweight/obesity. METHODS: We compared baseline and Year 3 school-level
      behavioral and weight status outcomes with paired t-tests adjusted for schools'
      socio-demographic characteristics. We used generalized estimating equations to
      examine the odds of overweight/obesity associated with program components.
      SETTING/PARTICIPANTS: Consecutive sample of 45 of 51 middle schools participating
      in the HC program with complete baseline and follow-up survey data including a
      subsample of 35 schools with measured anthropomentry for 5,665 7th grade
      students. INTERVENTION: Schools developed a multi-disciplinary team and
      implemented an obesity prevention curriculum, before and after school activities,
      environmental and policy changes and health promotions targeting a 5-2-1 theme:
      eat >= 5 servings/day of fruits and vegetables (FV), watch <= 2 hours of
      television (TV) and participate in >= 1 hours/day of physical activity (PA) on
      most days. MAIN OUTCOME MEASURES: 1) School-level percent of students achieving
      targeted behaviors and percent overweight/obese; and 2) individual odds of
      overweight/obesity. RESULTS: The percent achieving behavioral goals over three
      years increased significantly for FV: 16.4 to 19.4 (p = 0.001), TV: 53.4 to 58.2
      (p = 0.003) and PA: 37.1 to 39.9 (p = 0.02), adjusting for school size, baseline
      mean age and percent female, non-Hispanic White, and eligible for free and
      reduced price lunch. In 35 schools with anthropometry, the percent of
      overweight/obese 7th grade students decreased from 42.1 to 38.4 (p = 0.016).
      Having a team that met the HC definition was associated with lower odds of
      overweight/obesity (OR = 0.83, CI: 0.71-0.98). CONCLUSIONS AND RELEVANCE: The HC
      multi-component intervention demonstrated three-year improvements in weight
      related behaviors and weight status across diverse middle schools. Team building
      appears important to the program's effectiveness.

PMID- 26295838
TI  - Using Observational Data to Estimate the Effect of Hand Washing and Clean
      Delivery Kit Use by Birth Attendants on Maternal Deaths after Home Deliveries in
      Rural Bangladesh, India and Nepal.
AB  - BACKGROUND: Globally, puerperal sepsis accounts for an estimated 8-12% of
      maternal deaths, but evidence is lacking on the extent to which clean delivery
      practices could improve maternal survival. We used data from the control arms of
      four cluster-randomised controlled trials conducted in rural India, Bangladesh
      and Nepal, to examine associations between clean delivery kit use and hand
      washing by the birth attendant with maternal mortality among home deliveries.
      METHODS: We tested associations between clean delivery practices and maternal
      deaths, using a pooled dataset for 40,602 home births across sites in the three
      countries. Cross-sectional data were analysed by fitting logistic regression
      models with and without multiple imputation, and confounders were selected a
      priori using causal directed acyclic graphs. The robustness of estimates was
      investigated through sensitivity analyses. RESULTS: Hand washing was associated
      with a 49% reduction in the odds of maternal mortality after adjusting for
      confounding factors (adjusted odds ratio (AOR) 0.51, 95% CI 0.28-0.93). The
      sensitivity analysis testing the missing at random assumption for the multiple
      imputation, as well as the sensitivity analysis accounting for possible
      misclassification bias in the use of clean delivery practices, indicated that the
      association between hand washing and maternal death had been over estimated.
      Clean delivery kit use was not associated with a maternal death (AOR 1.26, 95% CI
      0.62-2.56). CONCLUSIONS: Our evidence suggests that hand washing in delivery is
      critical for maternal survival among home deliveries in rural South Asia,
      although the exact magnitude of this effect is uncertain due to inherent biases
      associated with observational data from low resource settings. Our findings
      indicating kit use does not improve maternal survival, suggests that the soap is
      not being used in all instances that kit use is being reported.

PMID- 26295839
TI  - Genetic and Informatic Analyses Implicate Kif12 as a Candidate Gene within the
      Mpkd2 Locus That Modulates Renal Cystic Disease Severity in the Cys1cpk Mouse.
AB  - We have previously mapped the interval on Chromosome 4 for a major polycystic
      kidney disease modifier (Mpkd) of the B6(Cg)-Cys1cpk/J mouse model of recessive
      polycystic kidney disease (PKD). Informatic analyses predicted that this interval
      contains at least three individual renal cystic disease severity-modulating loci
      (Mpkd1-3). In the current study, we provide further validation of these predicted
      effects using a congenic mouse line carrying the entire CAST/EiJ (CAST)-derived
      Mpkd1-3 interval on the C57BL/6J background. We have also generated a derivative
      congenic line with a refined CAST-derived Mpkd1-2 interval and demonstrated its
      dominantly-acting disease-modulating effects (e.g., 4.2-fold increase in total
      cyst area; p<0.001). The relative strength of these effects allowed the use of
      recombinants from these crosses to fine map the Mpkd2 effects to a <14 Mbp
      interval that contains 92 RefSeq sequences. One of them corresponds to the
      previously described positional Mpkd2 candidate gene, Kif12. Among the positional
      Mpkd2 candidates, only expression of Kif12 correlates strongly with the
      expression pattern of Cys1 across multiple anatomical nephron structures and
      developmental time points. Also, we demonstrate that Kif12 encodes a primary
      cilium-associated protein. Together, these data provide genetic and informatic
      validation of the predicted renal cystic disease-modulating effects of Mpkd1-3
      loci and implicate Kif12 as the candidate locus for Mpkd2. 

PMID- 26295841
TI  - Transient synovitis of the hip: which investigations are truly useful?
AB  - QUESTIONS UNDER STUDY/PRINCIPLES: To assess the usefulness of several laboratory
      and radiological investigations for the limping child with suspected transient
      synovitis of the hip. METHODS: The medical records of children admitted at our
      children's hospital for nontraumatic hip pain between 1999 and 2007 were
      retrospectively reviewed. During the study period, all children without a
      definite diagnosis after routine investigations in the emergency department were
      admitted and a specific work-up including antinuclear antibodies titre,
      rheumatoid factor, antistreptolysin O titre, Lyme disease serology and hip
      ultrasonography were obtained. Children were systematically re-evaluated 6 weeks
      after hospital discharge, with a clinical examination and radiological hip views.
      Patients were diagnosed with transient synovitis of the hip if an ultrasound
      confirmed hip effusion was present at time of admission, complete resolution of
      symptoms occurred without any specific treatment, and no other pathology of the
      hip was identified during follow-up. RESULTS: A total of 417 cases without
      definite diagnosis were admitted and were submitted to a specific work-up.
      Transient synovitis of the hip was subsequently diagnosed in 383 patients, septic
      arthritis in 1 patient, and Lyme arthritis in 1 patient. Thirty-two patients
      remained without diagnosis. No rheumatological condition was found. CONCLUSION:
      Our results suggest that most investigations performed during the initial work-up
      in patients suspected transient synovitis of the hip are unnecessary and should
      routinely include only white blood cell count, C-reactive protein, erythrocyte
      sedimentation rate, and hip radiography and ultrasonography. No further
      investigations are necessary during follow-up for transient synovitis of the hip
      in asymptomatic children.

PMID- 26295840
TI  - Genomic Copy Number Variations in the Genomes of Leukocytes Predict Prostate
      Cancer Clinical Outcomes.
AB  - Accurate prediction of prostate cancer clinical courses remains elusive. In this
      study, we performed whole genome copy number analysis on leukocytes of 273
      prostate cancer patients using Affymetrix SNP6.0 chip. Copy number variations
      (CNV) were found across all chromosomes of the human genome. An average of 152
      CNV fragments per genome was identified in the leukocytes from prostate cancer
      patients. The size distributions of CNV in the genome of leukocytes were highly
      correlative with prostate cancer aggressiveness. A prostate cancer outcome
      prediction model was developed based on large size ratio of CNV from the
      leukocyte genomes. This prediction model generated an average prediction rate of
      75.2%, with sensitivity of 77.3% and specificity of 69.0% for prostate cancer
      recurrence. When combined with Nomogram and the status of fusion transcripts, the
      average prediction rate was improved to 82.5% with sensitivity of 84.8% and
      specificity of 78.2%. In addition, the leukocyte prediction model was 62.6%
      accurate in predicting short prostate specific antigen doubling time. When
      combined with Gleason's grade, Nomogram and the status of fusion transcripts, the
      prediction model generated a correct prediction rate of 77.5% with 73.7%
      sensitivity and 80.1% specificity. To our knowledge, this is the first study
      showing that CNVs in leukocyte genomes are predictive of clinical outcomes of a
      human malignancy. 

PMID- 26295844
TI  - Nodal monoclonal CD5-positive B-lymphocytosis and toxoplasma lymphadenitis:
      another variant in the spectrum of infectious lymphadenitis in patients with
      chronic leukemia/small lymphocytic lymphoma.

PMID- 26295845
TI  - Rescue of Targeted Nonstem-Like Cells from Bystander Stem-Like Cells in Human
      Fibrosarcoma HT1080.
AB  - Cancer stem-like cells (CSCs) have been suggested to be the principal cause of
      tumor radioresistance, dormancy and recurrence after radiotherapy. However,
      little is known about CSC behavior in response to clinical radiotherapy,
      particularly with regard to CSC communication with bulk cancer cells. In this
      study, CSCs and nonstem-like cancer cells (NSCCs) were co-cultured, and defined
      cell types were chosen and irradiated, respectively, with proton microbeam. The
      bidirectional rescue effect in the combinations of the two cell types was then
      investigated. The results showed that out of all four combinations, only the
      targeted, proton irradiated NSCCs were protected by bystander CSCs and showed
      less accumulation of 53BP1, which is a widely used indicator for DNA double
      strand breaks. In addition, supplementation with c-PTIO, a specific nitric oxide
      scavenger, can show a similar effect on targeted NSCCs. These results, showed
      that the rescue effect of CSCs on targeted NSCCs involves nitric oxide in the
      process, suggesting that the cellular communication between CSCs and NSCCs may be
      important in determining the survival of tumor cells after radiation therapy. To
      our knowledge, this is the first report demonstrating a rescue effect of CSCs to
      irradiated NSCCs that may help us better understand CSC behavior in response to
      cancer radiotherapy. 

PMID- 26295847
TI  - Hg(OTf)2 Catalyzed Intramolecular 1,4-Addition of Donor-Acceptor Cyclopropenes to
      Arenes.
AB  - A Hg(OTf)2 catalyzed intramolecular arene 1,4-addition reaction of N-benzyl donor
      acceptor cyclopropenecarboxamides was developed to synthesize a series of
      [3.2.2]nonatriene derivatives. This novel reaction is also observed with
      silver(I) catalysts known to form metal carbene intermediates in competition with
      the Buchner reaction. 

PMID- 26295848
TI  - Instructional Insights: Audio Feedback as Means of Engaging the Occupational
      Therapy Student.
AB  - Constructivist learning approaches require faculty to engage students in the
      reflective learning process, yet students can begin to view this process as
      mundane and at times not engage in the process or utilize feedback provided. This
      article describes the results of applying audio feedback to overcome these
      obstacles in a practicum integration course. Student report and assignment
      performance indicated increased learning and engagement. The instructor found
      giving audio feedback more efficient than written feedback as it overcame
      inflection issues associated with the written word. Recorded files also
      alleviated additional student appointments for clarification of the feedback. 

PMID- 26295846
TI  - YAP1 Exerts Its Transcriptional Control via TEAD-Mediated Activation of
      Enhancers.
AB  - YAP1 is a major effector of the Hippo pathway and a well-established oncogene.
      Elevated YAP1 activity due to mutations in Hippo pathway components or YAP1
      amplification is observed in several types of human cancers. Here we investigated
      its genomic binding landscape in YAP1-activated cancer cells, as well as in non
      transformed cells. We demonstrate that TEAD transcription factors mediate YAP1
      chromatin-binding genome-wide, further explaining their dominant role as primary
      mediators of YAP1-transcriptional activity. Moreover, we show that YAP1 largely
      exerts its transcriptional control via distal enhancers that are marked by H3K27
      acetylation and that YAP1 is necessary for this chromatin mark at bound enhancers
      and the activity of the associated genes. This work establishes YAP1-mediated
      transcriptional regulation at distal enhancers and provides an expanded set of
      target genes resulting in a fundamental source to study YAP1 function in a normal
      and cancer setting. 

PMID- 26295849
TI  - Angioinvasive opportunistic filamentous mycoses in immunocompromised patients.
AB  - Immunocompromised individuals are at greater risk for disseminated fungal
      infections. Immunocompromised individuals in the community have increased because
      of medical advances, thereby increasing the incidence and prevalence of
      opportunistic mycoses. The following case series illustrates the importance of
      having a high clinical suspicion for skin manifestations concerning for deep
      fungal infections.

PMID- 26295850
TI  - Tobacco-associated yellow discoloration of upper lip hair: smoker's mustache.
AB  - BACKGROUND: Hair is susceptible to exogenous sources of discoloration. There are
      several exogenous etiologies for yellow hair discoloration, including tobacco.
      PURPOSE: We describe the clinical features of five men with tobacco-associated
      yellow discoloration of their mustache, a condition known as "smoker's mustache."
      We also review the characteristics of men with tobacco-associated yellow
      discoloration of their scalp or mustache hair. MATERIALS AND METHODS: The
      features of five men with smoker's mustache are presented. Using PubMed, the
      following terms were searched and relevant citations assessed: 4-4'
      methylenedianiline, acid, dithranol, MDA, mustache, nicotine, picric, resorcin,
      smoker, tar, tobacco, and yellow. In addition, the literature on smoker's
      mustache is reviewed. RESULTS: Smoker's mustache was an incidental finding and
      not the reason for patients presenting for medical attention. The condition was
      asymptomatic. In our patients, 60% (3 of 5) also had tobacco-related clinical
      findings on the distal soft tissue and/or nails of their fingers. CONCLUSION:
      Smoker's mustache refers to tobacco-associated discoloration of the hair of the
      upper lip of men. It is an asymptomatic condition that usually presents as an
      incidental finding. Indeed, patients tend to be unaware of the condition until it
      is brought to their attention. In addition to hair manifestations, patients may
      also demonstrate other tobacco-associated skin and nail findings, particularly
      brown or yellow-brown discoloration of their fingertip and/or fingernail. We
      postulate that discontinuation of smoking would eventually result in spontaneous
      resolution of the condition. However, all of our patients were determined to
      continue smoking.

PMID- 26295851
TI  - What can U.S. dermatology learn from health care systems abroad? An observation
      of Taiwan's system of clinical efficiency as a possible model for increased
      patient access to care and affordability.
AB  - BACKGROUND: Difficulty in patient access to care and affordability are major
      problems faced by our dermatology specialty in the United States. However, Taiwan
      provides adequate and affordable dermatologic care for all of its citizens.
      Herein we describe our first-hand observations and findings of the outpatient
      dermatology experience in Taipei, and contrast it to the experience in the United
      States. OBSERVATION: In Taipei, Taiwan, we observed patient management,
      electronic documentation, and billing during outpatient dermatology visits in
      five settings: one academic hospital outpatient dermatology department, one
      academic hospital Information Technology department, and three private
      dermatologists' offices. Through our observations, we found that the dermatology
      specialty in Taiwan is able to overcome challenges with access to care and
      affordability through three key system features: (1) short yet frequent patient
      visits (2) close proximity of ancillary staff, and (3) an integrated and
      paperless electronic medical record and billing system. CONCLUSIONS: The Taiwan
      system is attained with some sacrifice, such as shorter time spent with patients
      and less personalized care. However, because this system can meet the basic
      dermatological needs of the entire population, possibly better than our current
      system, it behooves us to study the Taiwan system with respect and care.

PMID- 26295852
TI  - Widespread calciphylaxis and normal renal function: no improvement with sodium
      thiosulfate.
AB  - Although calciphylaxis generally occurs in patients with chronic renal failure,
      we present a patient with widespread calciphylaxis in the setting of normal renal
      function following renal transplant. IV and IL sodium thiosulfate injections were
      not beneficial in our patient. 

PMID- 26295853
TI  - Zosteriform metastasis of rectal adenocarcinoma: a case report.
AB  - Cutaneous metastases manifesting as zosteriform eruptions are uncommon. To our
      knowledge, we report the second case of zosteriform cutaneous metastasis arising
      from a rectal carcinoma in a 58-year-old man who presented with a painless
      popular eruption in the T12 dermatomal distribution nine months after his primary
      diagnosis of rectal carcinoma was made. Furthermore, we discuss a review of the
      literature regarding zosteriform cutaneous metastases and the possible
      pathogenesis of these lesions. 

PMID- 26295854
TI  - Pseudo-Kaposi sarcoma (acroangiodermatitis): occurring after bullous erysipelas.
AB  - Pseudo-Kaposi sarcoma is a benign reactive vascular proliferative disorder, which
      can be seen at any age. It occurs when the chronic venous pressure changes result
      in vascular proliferation in the upper and mid dermis. This disease is divided
      into two subtypes: the most frequent subtype is the Mali type and seen in early
      ages. The Mali type is seen in chronic venous insufficiency and in those patients
      with arteriovenous shunts. The rare subtype is the Stewart-Bluefarb type. This
      disease must be distinguished from Kaposi sarcoma because of their clinical
      resemblance. Herein, we present a patient with pseudo-Kaposi sarcoma, which
      developed after bullous erysipelas. 

PMID- 26295855
TI  - Acantholytic dermatosis of the vulva.
AB  - Acantholytic dermatosis of the vulva is a rare condition, presenting with papular
      eruption in the genital area without history of Darier disease or Hailey-Hailey
      disease. We report a case with a papular pruritic eruption in the region of the
      vulva, coalescing into plaques. Biopsy specimen showed irregular acanthosis with
      an area of split-like bullous formation in the deeper part of the epidermis, as
      well as acantholytic cells, marked hypergranulosis and hyperkeratosis, compatible
      with the rare diagnosis of acantholytic dermatosis of the vulva. We review the
      clinical and histological characteristics of this uncommon disease. 

PMID- 26295856
TI  - Adnexal polyp in a newborn baby.
AB  - Birthmarks can frequently be seen in newborn babies, but their etiopathogenesis
      is often unclear. These lesions can be divided into three groups: vascular
      birthmarks, pigmented birthmarks, and birthmarks resulting in abnormal
      development. Some birthmarks may require further analysis and clinical follow-up
      in order to rule out underlying defects, malignant potential, or correlation with
      syndromic diseases. Presented here is the case of a newborn baby with two
      simultaneous birthmarks: an adnexal polyp and a nevus anemicus. Adnexal polyps
      are considered an uncommon clinical observation

PMID- 26295857
TI  - Linear adamantinoid basal cell carcinoma in the axilla.
AB  - We present a case of asymptomatic deeply pigmented linear plaque with rolled
      borders that we encountered in an elderly Indian male over a sun protected site,
      the left axilla. The diagnosis of linear adamantinoid basal cell carcinoma was
      confirmed on histopathological examination. 

PMID- 26295858
TI  - Ulcerated erythematous plaque on the right breast localized to the previously
      irradiated area.
AB  - Radiation recall dermatitis (RRD) is an inflammatory reaction limited to
      previously irradiated areas and occurs following the subsequent administration of
      a drug. Herein, we present a patient with severe RRD associated with pain and
      necrosis.

PMID- 26295859
TI  - Sporotrichoid Mycobacterium marinum infection in an elderly woman.
AB  - We describe the case of an elderly woman who acquired a Mycobacterium marinum
      infection following skin exposure to the bacteria through a small wound on her
      right ring finger, obtained while preparing fish. The resultant sporotrichoid
      nodules of the right hand and the distal forearm, refractory to the initial
      therapy with doxycycline and rifampicin, were successfully treated with oral
      regimen of clarithromycin. 

PMID- 26295860
TI  - Pachydermoperiostosis, a unique entity with distinctive clinical features.
AB  - Pachydermoperiostosis, which occurs more frequently in men, is a rare entity with
      distinctive clinical features and an insidious onset.. We report the case of a 30
      year-old man with a one-year history of acropachy, arthralgias, hiperhidrosis,
      and progressive skin thickening of the face and scalp. The radiological findings
      were consistent with periostosis and the histopathological analysis from a facial
      skin biopsy showed a pandermal increase in the thickness and number of collagen
      bundles. The pathogenesis of PDP is currently unknown, although an increased
      secretion of prostaglandin E2 (PGE2), which stimulates the overexpression of
      vascular endothelial growth factor (VEGF), has been suggested as a major factor.
      No specific treatment exists; however, in most cases, the disease tends to
      stabilize over time.

PMID- 26295861
TI  - Hyperpigmentation and atrophy in folds as cutaneous manifestation in a case of
      mitochondrial myopathy.
AB  - Mitochondrial myopathies are inborn metabolism defect diseases manifested by
      symptoms reflecting failure of the final step in the mitochondrial respiratory
      chain. Clinical expression of these conditions can vary widely, but typically
      includes organ systems with a high energy demand, such as striated muscle,
      myocardium, and nervous and liver tissues. In contrast, cutaneous manifestations
      are rare and are non-specific, most commonly presenting as pigmentation
      disorders. In this case report, we present a case of Alpers syndrome accompanied
      by hyperpigmentation and atrophy in skin folds. 

PMID- 26295862
TI  - Dramatic hyperpigmentation of keloids after intralesional triamcinolone acetonide
      injection.

PMID- 26295863
TI  - Rosacea-like eruption due to topical pimecrolimus.
AB  - Topical calcineurin inhibitors have been used outside their approved indications
      for a number of conditions, including topical steroid-induced rosacea. However,
      tacrolimus ointment itself has been reported to trigger rosacea in a small number
      of cases. We report a case of a rosacea-like eruption in a 39-year-old woman
      occurring after the use of pimecrolimus cream for 12 months for atopic
      dermatitis. Withdrawal of pimecrolimus combined with treatment with oral
      lymecycline, topical metronidazole, and an emollient resulted in resolution of
      the eruption. There have been 5 previously reported cases of a topical
      pimecrolimus-induced rosacea-like eruption suggesting that this rare side-effect
      may be a class effect of all topical calcineurin inhibitors. Dermatologists
      prescribing these drugs should be aware of this uncommon complication and may
      wish to warn patients of its occurrence as a potential side-effect when using
      topical calcineurin inhibitors in facial skin in adults. 

PMID- 26295865
TI  - Palmoplantar hyperkeratotic lesions: a rare presentation of lichen planus.
AB  - Palmoplantar lichen planus is a localized and rare subtype of lichen planus (LP)
      often underdiagnosed. Several morphological types of palmoplantar lesions have
      been defined in LP. We present an unusual case of the palmoplantar kyperkeratotic
      variant of LP. Histopathology examination confirmed our diagnosis. We emphasize
      the importance of this rare entity in the differential diagnosis of palmoplantar
      dermatoses. 

PMID- 26295864
TI  - Systemic contact dermatitis due to amethocaine following digital rectal
      examination.
AB  - Systemic contact dermatitis is a dermatitis that may occur in previously
      sensitized individuals when they are re-exposed to the allergen. Although many
      drugs have been implicated as a cause of systemic contact dermatitis, local
      anesthetics derived from caines have been rarely reported. We present a case of
      systemic contact dermatitis after a digital rectal examination with a urological
      lubricant containing amethocaine.

PMID- 26295866
TI  - Efficient non-negative constrained model-based inversion in optoacoustic
      tomography.
AB  - The inversion accuracy in optoacoustic tomography depends on a number of
      parameters, including the number of detectors employed, discrete sampling issues
      or imperfectness of the forward model. These parameters result in ambiguities on
      the reconstructed image. A common ambiguity is the appearance of negative values,
      which have no physical meaning since optical absorption can only be higher or
      equal than zero. We investigate herein algorithms that impose non-negative
      constraints in model-based optoacoustic inversion. Several state-of-the-art non
      negative constrained algorithms are analyzed. Furthermore, an algorithm based on
      the conjugate gradient method is introduced in this work. We are particularly
      interested in investigating whether positive restrictions lead to accurate
      solutions or drive the appearance of errors and artifacts. It is shown that the
      computational performance of non-negative constrained inversion is higher for the
      introduced algorithm than for the other algorithms, while yielding equivalent
      results. The experimental performance of this inversion procedure is then tested
      in phantoms and small animals, showing an improvement in image quality and
      quantitativeness with respect to the unconstrained approach. The study performed
      validates the use of non-negative constraints for improving image accuracy
      compared to unconstrained methods, while maintaining computational efficiency. 

PMID- 26295867
TI  - Nitrous Oxide and Methane Fluxes Following Ammonium Sulfate and Vinasse
      Application on Sugar Cane Soil.
AB  - This study aimed to quantify nitrous oxide (N2O) and methane (CH4) emission/sink
      response from sugar cane soil treated with fertilizer nitrogen (N) and vinasse
      applied separately or in sequence, the latter being investigated with regard to
      the time interval between applications for a possible effect on emissions. The
      study was carried out in a traditional area of unburned sugar cane in Sao Paulo
      state, Brazil. Two levels of N fertilization (0 and 100 kg N ha(-1)) with no
      added vinasse and combined with vinasse additions at different times (100 m(-3)
      ha(-1) at 3 and 15 days after N fertilization) were evaluated. Methane and N2O
      fluxes were monitored for 211 days. On average, the soil was a sink for CH4,
      which was not affected by the treatments. Emissions of N2O were induced by N
      fertilizer and vinasse applications. For ammonium sulfate, 0.6% of the added N
      was emitted as N2O, while for vinasse, this ranged from 1.0 to 2.2%. Changes in
      N2O fluxes were detected the day after application of vinasse on the N fertilized
      areas, but although the emission factor (EF) was 34% greater, the EF was not
      significantly different from fertilizer N alone. Nevertheless, we recommend to
      not apply vinasse after N fertilization to avoid boosting N2O emissions. 

PMID- 26295868
TI  - Cyclophosphamide and tucotuzumab (huKS-IL2) following first-line chemotherapy in
      responding patients with extensive-disease small-cell lung cancer.
AB  - The humanized KS-interleukin-2, tucotuzumab (huKS-IL2; EMD 273066), is an EpCAM
      specific immunocytokine with reported immunologic activity in combination with
      cyclophosphamide. This Phase 2, randomized, open-label study compared
      tucotuzumab/cyclophosphamide, administered as maintenance, with best supportive
      care (BSC) in patients with extensive-disease small-cell lung cancer (ED-SCLC)
      who responded to first-line platinum-based chemotherapy with/without prophylactic
      cranial irradiation (PCI). Patients received cyclophosphamide (300 mg/m, Day 1 of
      every 3-week cycle), followed by tucotuzumab (1.5 mg/m, Days 2-4) until disease
      progression. The primary endpoint was 6-month progression-free survival (PFS);
      the secondary objectives included overall survival (OS), treatment response, and
      safety. The 6-month PFS rate was lower in the tucotuzumab/cyclophosphamide group
      (n=64) than in the BSC group (n=44): 6.4 versus 12.2% [hazard ratio (HR): 0.98;
      80% confidence interval (CI): 0.74-1.31]. HRs for PFS, time to progression, and
      OS indicated a similar risk of disease progression and death in both groups and
      best overall responses were generally comparable. For patients with previous PCI
      (n=26), there was a nonsignificant trend toward prolonged median PFS (1.7 vs. 1.5
      months; HR: 0.60; 80% CI: 0.33-1.11) and OS (21.5 vs. 14.3 months; HR: 0.58; 80%
      CI: 0.31-1.05) in the tucotuzumab/cyclophosphamide group. Adverse events were
      more frequent with tucotuzumab/cyclophosphamide (92.2%) than with BSC (47.7%).
      Tucotuzumab/cyclophosphamide was well tolerated in ED-SCLC patients, but did not
      show PFS or OS benefits compared with BSC. The observed trend toward prolonged
      PFS and OS in the subgroup of patients receiving previous PCI may support further
      confirmation in a larger population. 

PMID- 26295869
TI  - Salvage therapy with bortezomib and dexamethasone in elderly patients with
      relapsed/refractory multiple myeloma.
AB  - Bortezomib-dexamethasone (bort-dex) is effective for relapsed/refractory (R/R)
      multiple myeloma, but few data are available for elderly patients. The aim of
      this study was to evaluate efficacy and toxicity of bort-dex in elderly R/R MM
      patients. We evaluated 81 R/R MM patients treated with bort-dex. Eight of them
      had light-chain disease. The median age of the patients was 73 years (range 65-89
      years). All patients were R/R MM patients and had been treated with melphalan and
      prednisone with or without thalidomide or bortezomib in the first line or with
      lenalidomide and dexamethasone in the second line. The median number of previous
      lines was 2. Thirty-nine (48%) patients received bortezomib intravenously and 42
      (52%) patients received bortezomib subcutaneously. The median number of bort-dex
      cycles was 6 (range 1-11). Fifty-three (65.4%) patients achieved at least a
      partial response, including eight (11%) patients with complete response and nine
      (12.5%) patients with very good partial responses. The median duration of
      response, time to next therapy and treatment-free intervals were 8, 11 and 5
      months. Duration of response was significantly longer for patients achieving
      complete response/very good partial response than for those achieving partial
      response (7.3 vs. 3.8 months, P=0.03). After a median follow-up of 24 months, 78
      patients showed disease progression and 70 died. The median time to progression,
      progression-free survival and overall survival were 8.9, 8.7 and 22 months,
      respectively. Peripheral neuropathy occurred in 38 (47%) patients. Our data
      highlight that bort-dex is effective and tolerable in fit elderly patients, thus
      justifying the efforts for deeper responses. However, awareness of short-lived
      responses to bort-dex should lead to a thorough evaluation of the need for
      maintenance. 

PMID- 26295870
TI  - Mn-Doped Multinary CIZS and AIZS Nanocrystals.
AB  - Multinary nanocrystals (CuInS2, CIS, and AgInS2, AIS) are widely known for their
      strong defect state emission. On alloying with Zn (CIZS and AIZS), stable and
      intense emission tunable in visible and NIR windows has already been achieved. In
      these nanocrystals, the photogenerated hole efficiently moves to the defect
      induced state and recombines with the electron in the conduction band. As a
      result, the defect state emission is predominantly observed without any band edge
      excitonic emission. Herein, we report the doping of the transition-metal ion Mn
      in these nanocrystals, which in certain compositions of the host nanocrystals
      quenches this strong defect state emission and predominantly shows the spin-flip
      Mn emission. Though several Mn-doped semiconductor nanocrystals are reported in
      the literature, these nanocrystals are of its first kind that can be excited in
      the visible window, do not contain the toxic element Cd, and provide efficient
      emission. Hence, when Mn emission is required, these multinary nanocrystals can
      be the ideal versatile materials for widespread technological applications. 

PMID- 26295871
TI  - Multifunctional Doped Semiconductor Nanocrystals.
AB  - Multifunctional nanomaterials with combined magnetic and optical properties
      remain one of the most demanded materials in upcoming research. To obtain these
      materials, we report here several doped semiconductor nanocrystals that
      simultaneously show tunable emission in a visible and NIR spectral window, above
      room-temperature ferromagnetism, and improved conductivity. These nanocrystals
      are designed by inserting Ni(II) as a dopant in various semiconducting hosts with
      binary, alloyed, and ternary composition, and the induced multifunctional
      properties are observed to be stable and reproducible. These semiconducting
      materials combined with fluorescence and magnetic properties would be useful for
      a wide range of applications spanning from life science to modern developing
      device technology. 

PMID- 26295872
TI  - A Reaction Accelerator: Mid-infrared Strong Field Dissociation Yields Mode
      Selective Chemistry.
AB  - Mode-selective chemistry has been a dream of chemists since the advent of the
      laser in the 1970s. Despite intense effort, this goal has remained elusive due to
      efficient energy randomization in polyatomic molecules. Using ab initio molecular
      dynamics calculations, we show that the interaction of molecules with intense,
      ultrashort mid-infrared laser pulses can accelerate and promote reactions that
      are energetically and entropically disfavored, owing to efficient kinetic energy
      pumping into the corresponding vibrational mode(s) by the laser field. In a test
      case of formyl chloride ion photodissociation, the reactions are ultimately
      complete under field-free conditions within 500 fs after the laser pulse, which
      effectively overcomes competition from intramolecular vibrational energy
      redistribution (IVR). The approach is quite general and experimentally accessible
      using currently available technology. 

PMID- 26295873
TI  - Quantum Dynamical Simulations as a Tool for Predicting Photoinjection Mechanisms
      in Dye-Sensitized TiO2 Solar Cells.
AB  - On the basis of a time-dependent self-consistent density functional tight-binding
      (TD-DFTB) approach, we present a novel method able to capture the differences
      between direct and indirect photoinjection mechanisms in a fully atomistic
      picture. A model anatase TiO2 nanoparticle (NP) functionalized with different
      dyes has been chosen as the object of study. We show that a linear dependence of
      the rate of electron injection with respect to the square of the applied field
      intensity can be viewed as a signature of a direct electron injection mechanism.
      In addition, we show that the nature of the photoabsorption process can be
      understood in terms of orbital population dynamics occurring during
      photoabsorption. Dyes involved in both direct (type-I) and indirect (type-II)
      mechanisms were studied to test the predictive power of this method. 

PMID- 26295874
TI  - Multiscale Theoretical Modeling of Plasmonic Sensing of Hydrogen Uptake in
      Palladium Nanodisks.
AB  - We study theoretically the optical properties of palladium nanodisks during
      hydrogen uptake. A combination of an ab initio quantum mechanical description of
      the Pd-H dielectric properties and a full electrodynamical study of light
      scattering in the H-modified Pd nanodisks allows us to trace the shift of the
      localized surface plasmon as a function of the H concentration in the Pd-H disk.
      We follow the evolution of the plasmon peak energy for different admixtures of
      the Pd-H alpha and beta phases and interpret quantitatively the experimental
      sensitivity of the plasmon energy shift to the structural inhomogeneity upon H
      absorption. Our multiscale theoretical framework provides a solid background for
      plasmonic sensing of structural domains, as well as for identifying H saturation
      conditions in metal hydride systems. 

PMID- 26295876
TI  - Orientation Sensing with Color Using Plasmonic Gold Nanorods and Assemblies.
AB  - Colorimetric analysis of broadband illumination scattered from isolated gold
      nanorods and reduced symmetry Dolmen structures provide a visible measure of the
      local nanoscale orientation of the nanostructures relative to the laboratory
      frame of reference. Polarized dark-field scattering microscopy correlated with
      scanning electron microscopy of low and high aspect ratio gold nanorods
      demonstrated accuracies of 2.3 degrees, which is a 5-fold improvement over
      photothermal and defocused imaging methods. By assigning the three color channels
      of the imaging detector (red, green, and blue) to the plasmon resonance
      wavelengths of the nanostructure, the quantitative display of orientation
      improved by 200%. The reduced symmetry of a gold nanorod Dolmen structure further
      improved the sensitivity of colorimetric orientation by a factor of 2 due to the
      comparative intensities of the resonances. Thus the simplicity, high accuracy,
      and sensitivity of visual colorimetric sensing of local nanoscale orientation
      holds promise for high throughput, inexpensive structure and dynamics studies in
      biology and material science. 

PMID- 26295875
TI  - Fast Crystal Growth Induces Mobility and Tension in Supercooled o-Terphenyl.
AB  - A photobleaching method was used to measure the reorientation of dilute probes in
      liquid o-terphenyl near a crystal growth front. Near the glass-transition
      temperature Tg, mobility in the supercooled liquid was enhanced within ~10 MUm of
      the crystal growth front, by as much as a factor of 4. This enhanced mobility
      appears to be caused by tension created in the sample as a result of the density
      difference between the supercooled liquid and crystal. The maximum observed
      mobility enhancement corresponds to a tension of about -8 MPa, close to the
      cavitation limit for liquid o-terphenyl. Whereas the observed mobility near the
      growing crystal is not large enough to explain the extraordinary fast crystal
      growth observed near Tg in o-terphenyl and some other low-molecular-weight
      glassformers, these observations suggest that cavitation or fracture plays a key
      role in releasing tension and allowing fast crystal growth to occur at a steady
      rate. 

PMID- 26295877
TI  - Two-Dimensional Electronic Spectroscopy in the Ultraviolet Wavelength Range.
AB  - Coherent two-dimensional (2D) spectroscopies conducted at visible and infrared
      wavelengths are having a transformative impact on the understanding of numerous
      processes in condensed phases. The extension of 2D spectroscopy to the
      ultraviolet spectral range (2DUV) must contend with several challenges, including
      the attainment of adequate laser bandwidth, interferometric phase stability, and
      the suppression of undesired nonlinearities in the sample medium. Solutions to
      these problems are motivated by the study of a wide range of biological systems
      whose lowest-frequency electronic resonances are found in the UV. The development
      of 2DUV spectroscopy also makes possible the attainment of new insights into
      elementary chemical reaction dynamics (e.g., electrocyclic ring opening in
      cycloalkenes). Substantial progress has been made in both the implementation and
      application of 2DUV spectroscopy in the past several years. In this Perspective,
      we discuss 2DUV methodology, review recent applications, and speculate on what
      the future will hold. 

PMID- 26295878
TI  - Hydrogenation of Ferrimagnetic Graphene on a Co Surface: Significant Enhancement
      of Spin Moments by C-H Functionality.
AB  - Using ab initio density functional theory, we present a novel way of
      simultaneously enhancing the induced magnetic moment and opening up the band gap
      of a graphene sheet supported on ferromagnetic transition metal surface.
      Specifically, we have demonstrated that by simply hydrogenating graphene
      supported on ferromagnetic Co surface at saturation coverage, (i) there is a six
      fold increase in the magnitude of the induced magnetic moment compared with the
      pristine graphene on the Co surface and (ii) for both the spin-up and the spin
      down channels there is a band gap opening at the K-point of the Brillouin zone. 

PMID- 26295879
TI  - Near-Quantitative Agreement of Model-Free DFT-MD Predictions with XAFS
      Observations of the Hydration Structure of Highly Charged Transition-Metal Ions.
AB  - First-principles dynamics simulations (DFT, PBE96, and PBE0) and electron
      scattering calculations (FEFF9) provide near-quantitative agreement with new and
      existing XAFS measurements for a series of transition-metal ions interacting with
      their hydration shells via complex mechanisms (high spin, covalency, charge
      transfer, etc.). This analysis does not require either the development of
      empirical interparticle interaction potentials or structural models of hydration.
      However, it provides consistent parameter-free analysis and improved agreement
      with the higher-R scattering region (first- and second-shell structure, symmetry,
      dynamic disorder, and multiple scattering) for this comprehensive series of ions.
      DFT+GGA MD methods provide a high level of agreement. However, improvements are
      observed when exact exchange is included. Higher accuracy in the pseudopotential
      description of the atomic potential, including core polarization and reducing
      core radii, was necessary for very detailed agreement. The first-principles
      nature of this approach supports its application to more complex systems. 

PMID- 26295880
TI  - Proton Momentum Distribution and Diffusion Coefficient in Water: Two Sides of the
      Same Coin?
AB  - Water, the prototype of a liquid to ordinary people, is the most anomalous liquid
      to physicists, showing regions of the temperature-density (T,rho) plane where its
      microscopic structure, diffusion coefficient, and density have anomalous
      behaviors. Structural anomalies occur over a broad bell-shaped T,rho region. This
      region contains, as a matryoshka, two smaller regions, one delimiting dynamical
      and the other delimiting thermodynamic anomalies. Water anomalous behavior in
      each of these regions manifests itself as a decrease of order or an increase of
      the diffusion coefficient upon increasing pressure and as a decrease of density
      upon cooling. Here, we show that the radial momentum distribution of water
      protons and their mean kinetic energy have a peculiar, theoretically unpredicted
      anomaly in the region of dynamical anomalies. This anomaly can be rationalized as
      due to two distinct "families" of water protons, experiencing quite distinct
      local environments, leading to an enhancement of the momentum fluctuations along
      with an increase of kinetic energy. 

PMID- 26295881
TI  - Probe Position-Dependent Counterion Dynamics in DNA: Comparison of Time-Resolved
      Stokes Shift of Groove-Bound to Base-Stacked Probes in the Presence of Different
      Monovalent Counterions.
AB  - Time-resolved fluorescence Stokes shifts (TRFSS) of 4',6-diamidino-2-phenylindole
      (DAPI) inside the minor groove of DNA are measured in the presence of three
      different monovalent counterions: sodium (Na(+)), rubidium (Rb(+)), and
      tetrabutylammonium (TBA(+)). Fluorescence up-conversion and time-correlated
      single photon counting are combined to obtain the time-resolved emission spectra
      (TRES) of DAPI in DNA from 100 fs to 10 ns. Time-resolved Stokes shift data
      suggest that groove-bound DAPI can not sense the counterion dynamics because the
      ions are displaced by DAPI far from the probe-site. However, when these results
      are compared to the earlier base-stacked coumarin data, the same ions are found
      to affect the nanosecond dynamics significantly. This suggests that the ions come
      close to the probe-site, such that they can affect the dynamics when measured by
      base-stacked coumarin. These results support previous molecular dynamics (MD)
      simulation data of groove-bound and base-stacked probes inside DNA. 

PMID- 26295883
TI  - Concerted and Sequential Proton Transfer Mechanisms in Water-Separated Acid-Base
      Encounter Pairs.
AB  - The proton transfer mechanisms involved inside aqueous, solvent-separated
      encounter complexes between phenol and carboxyl moieties are studied using ab
      initio molecular dynamics and computational time-resolved vibrational
      spectroscopy. This model framework can be viewed as a ground-state analog of the
      excited-state proton transfer reactions that have been actively investigated
      using ultrafast spectroscopy. Three qualitatively distinct proton transfer
      pathways are observed in the simulations. These can be described as direct
      concerted, direct sequential, and through bulk transfers. The primary difference
      between the sequential and concerted mechanism is the involvement of a reaction
      intermediate in which the proton fluctuates for several picoseconds through the
      hydrogen bonds connecting donor and acceptor but resides primarily on an
      intervening water molecule in the encounter complex. These results contribute to
      our molecular level understanding of the diverse processes involved in proton
      transfer within water-separated encounter complexes. 

PMID- 26295882
TI  - Bound 1D Excitons in Single CdSe Quantum Wires.
AB  - Photogenerated electron-hole pairs are observed to be bound as 1D excitons in
      CdSe quantum wires (QWs) at room temperature. Microscopy experiments performed on
      dilute samples of CdSe QWs prepared on coverslips with patterned electrodes
      reveal that there is no change in either the overall photoluminescence (PL)
      intensity or the distribution of the PL intensity with the application of an
      external electric field. Changes in the PL intensity, and thus evidence for
      separate charge carriers within the QWs, are observed only for concentrated
      samples. In these concentrated samples, a thin film of other compounds, including
      trioctylphosphine oxide and a bismuth salt formed in the synthesis, is observed
      to encompass the QWs. The separate charge carriers that influence the PL
      intensity are attributed to the other compounds in the sample. 

PMID- 26295884
TI  - Activity and Synergy Effects on a Cu/ZnO(0001) Surface Studied Using First
      Principle Thermodynamics.
AB  - Using first-principle thermodynamics, we have studied surface phase diagrams of
      Cu substitutional ZnO(0001) surfaces under industrial conditions. On the one
      hand, the Cu substituted on Zn sites can promote efficient formation of oxygen
      vacancies on the ZnO(0001) surface. It can improve the activity on the
      Cu/ZnO(0001) surface. On the other hand, metallic monolayers containing certain
      Cu and Zn atoms can be also formed, accompanied by the oxygen vacancies
      formation. We have further investigated CO2 adsorption and reduction on these
      metallic monolayers. These metallic monolayers prefer to have an intermediate
      binding strength with the CO2 molecule. The intermediate binding strength was
      expected to be optimized for subsequent CO2 reduction. We have performed further
      studies and demonstrated successfully the improved catalysis for the subsequent
      CO2 reduction on these metallic monolayers. The relevant mechanism can be
      interpreted with the second synergy effect. The d-band states of these metallic
      monolayers, supported on the ZnO(0001) surface, are tuned to shift upward, that
      is, more close to Fermi level. Therefore, these metallic monolayers indeed
      exhibit promoted catalysis, in comparison with reported metallic surfaces in the
      literature. 

PMID- 26295885
TI  - Temperature-Volume Entropic Model for Viscosities and Structural Relaxation Times
      of Glass Formers.
AB  - In this Letter, an entropic model recently formulated by Mauro et al. for the
      temperature dependence of viscosity in glass-forming materials is generalized to
      describe the temperature-volume dependences of viscosities and structural
      relaxation times near the glass transition. It is found that the generalization
      shows limitations of its temperature precursor. The extended model describes well
      the structural dielectric relaxation times taualpha(T,V) of supercooled van der
      Waals liquids. The obtained results are discussed in the context of the
      thermodynamic scaling law for molecular dynamics of viscous systems. 

PMID- 26295886
TI  - Ligand-Induced Stability of Gold Nanoclusters: Thiolate versus Selenolate.
AB  - Thiolate-protected gold nanoclusters have attracted considerable attention as
      building blocks for new functional materials and have been extensively
      researched. Some studies have reported that changing the ligand of these gold
      nanoclusters from thiolate to selenolate increases cluster stability. To confirm
      this, in this study, we compare the stabilities of precisely synthesized
      [Au25(SC8H17)18](-) and [Au25(SeC8H17)18](-) against degradation in solution,
      thermal dissolution, and laser fragmentation. The results demonstrate that
      changing the ligand from thiolate to selenolate increases cluster stability in
      reactions involving dissociation of the gold-ligand bond but reduces cluster
      stability in reactions involving intramolecular dissociation of the ligand. These
      results reveal that using selenolate ligands makes it possible to produce gold
      clusters that are more stable against degradation in solution than thiolate
      protected gold nanoclusters. 

PMID- 26295887
TI  - Probing the Structure of Salt Water under Confinement with First-Principles
      Molecular Dynamics and Theoretical X-ray Absorption Spectroscopy.
AB  - We investigated the structure of liquid water around cations (Na(+)) and anions
      (Cl(-)) confined inside of a (19,0) carbon nanotube with first-principles
      molecular dynamics and theoretical X-ray absorption spectroscopy (XAS). We found
      that the ions preferentially reside near the interface between the nanotube and
      the liquid. Upon confinement, the XAS signal of water molecules surrounding Na(+)
      exhibits enhanced pre-edge and reduced post-edge features with respect to that of
      pure water, at variance with the solvation shell of Na(+) in bulk water.
      Conversely, the first solvation shell of confined Cl(-) has a main-edge intensity
      comparable to that of bulk solvated Cl(-), likely as a result of a high number of
      acceptor hydrogen bonds in the first solvation shell. Confined nonsolvating water
      molecules exhibit bulk-like or water-monomer-like properties, depending on
      whether they belong to core or interfacial layers, respectively. 

PMID- 26295888
TI  - Excitation Energy-Transfer Dynamics of Brown Algal Photosynthetic Antennas.
AB  - Fucoxanthin-chlorophyll-a/c protein (FCP) complexes from brown algae Cladosiphon
      okamuranus TOKIDA (Okinawa Mozuku in Japanese) contain the only species of
      carbonyl carotenoid, fucoxanthin, which exhibits spectral characteristics
      attributed to an intramolecular charge-transfer (ICT) property that arises in
      polar environments due to the presence of the carbonyl group in its polyene
      backbone. Here, we investigated the role of the ICT property of fucoxanthin in
      ultrafast energy transfer to chlorophyll-a/c in brown algal photosynthesis using
      femtosecond pump-probe spectroscopic measurements. The observed excited-state
      dynamics show that the ICT character of fucoxanthin in FCP extends its absorption
      band to longer wavelengths and enhances its electronic interaction with
      chlorophyll-a molecules, leading to efficient energy transfer from fucoxanthin to
      chlorophyll-a. 

PMID- 26295889
TI  - Parallel Pool Analysis of Transient Spectroscopy Reveals Origins of and
      Perspectives for ZnO Hybrid Solar Cell Performance Enhancement Using
      Semiconducting Surfactants.
AB  - Recently, the performance of ZnO nanocrystals as an electron acceptor in a solar
      cell device was significantly increased by a semiconducting surfactant. Here we
      show, using transient absorption spectroscopy and a parallel pool analysis, that
      changes in the quantum efficiency of charge generation account for the
      performance variation among semiconducting-surfactant-coated, surfactant-coated,
      and uncoated ZnO nanoparticles. We demonstrate that even better surfactant design
      to suppress fast recombination could still lead to a further doubling of device
      efficiency. 

PMID- 26295890
TI  - A Covalent Organic Framework that Exceeds the DOE 2015 Volumetric Target for H2
      Uptake at 298 K.
AB  - Physisorption in porous materials is a promising approach for meeting H2 storage
      requirements for the transportation industry, because it is both fully reversible
      and fast at mild conditions. However, most current candidates lead to H2 binding
      energies that are too weak (leading to volumetric capacity at 298 K of <10 g/L
      compared to the DOE 2015 Target of 40 g/L). Using accurate quantum mechanical
      (QM) methods, we studied the H2 binding energy to 48 compounds based on various
      metalated analogues of five common linkers for covalent organic frameworks
      (COFs). Considering the first transition row metals (Sc though Cu) plus Pd and
      Pt, we find that the new COF-301-PdCl2 reaches 60 g total H2/L at 100 bar, which
      is 1.5 times the DOE 2015 target of 40 g/L and close to the ultimate (2050)
      target of 70 g/L. The best current materials, MOF-200 and MOF-177, are predicted
      to store 7.6 g/L (0.54 wt % excess) and 9.6 g/L (0.87 wt % excess), respectively,
      at 298 K and 100 bar compared with 60 g/L (4.2 wt % excess) for COF-301-PdCl2. 

PMID- 26295891
TI  - Depth-Dependent Heterogeneity in Membranes by Fluorescence Lifetime Distribution
      Analysis.
AB  - Biological membranes display considerable anisotropy due to differences in
      composition, physical characteristics, and packing of membrane components. In
      this Letter, we have demonstrated the environmental heterogeneity along the
      bilayer normal in a depth-dependent manner using a number of anthroyloxy fatty
      acid probes. We employed fluorescence lifetime distribution analysis utilizing
      the maximum entropy method (MEM) to assess heterogeneity. Our results show that
      the fluorescence lifetime heterogeneity varies considerably depending on
      fluorophore location along the membrane normal (depth), and it is the result of
      the anisotropic environmental heterogeneity along the bilayer normal.
      Environmental heterogeneity is reduced as the reporter group is moved from the
      membrane interface to a deeper hydrocarbon region. To the best of our knowledge,
      our results constitute the first experimental demonstration of anisotropic
      heterogeneity in bilayers. We conclude that such graded environmental
      heterogeneity represents an intrinsic characteristics of the membrane bilayer and
      envisage that it has a role in the conformation and orientation of membrane
      proteins and their function. 

PMID- 26295892
TI  - Surface Plasmon Resonance Imaging: What Next?
AB  - This Perspective discusses recent advances in the field of surface plasmon
      resonance imaging (SPRi) for the label-free, multiplex, and sensitive study of
      biomolecular systems. Large efforts have been made during the past decade with
      the aim of developing even more sensitive and specific SPRi-based platforms.
      Metal nanostructures have been used to enhance SPRi sensitivity and to build a
      specific SPR-active surface, while special effects such as long-range SPR have
      been investigated to develop more effective SPRi platforms. Here, we review some
      of the significant work performed with SPRi for the ultrasensitive detection of
      biomolecular systems and provide a perspective on the challenges that need to be
      overcome to enable the wide use of SPRi in emerging key areas such as health
      diagnostics and antidoping controls. 

PMID- 26295893
TI  - Computation of Two-Dimensional Spectra Assisted by Compressed Sampling.
AB  - The computation of scientific data can be very time-consuming, even if they are
      ultimately determined by a small number of parameters. The principle of
      compressed sampling suggests that for typical data we can achieve a considerable
      decrease in the computation time by avoiding the need to sample the full data
      set. We demonstrate the usefulness of this approach at the hand of two
      dimensional (2-D) spectra in the context of ultrafast nonlinear spectroscopy of
      biological systems where numerical calculations are highly challenging due to the
      considerable computational effort involved in obtaining individual data points. 

PMID- 26295894
TI  - Compressed Sensing for Multidimensional Spectroscopy Experiments.
AB  - Compressed sensing is a processing method that significantly reduces the number
      of measurements needed to accurately resolve signals in many fields of science
      and engineering. We develop a two-dimensional variant of compressed sensing for
      multidimensional spectroscopy and apply it to experimental data. For the model
      system of atomic rubidium vapor, we find that compressed sensing provides an
      order-of-magnitude (about 10-fold) improvement in spectral resolution along each
      dimension, as compared to a conventional discrete Fourier transform, using the
      same data set. More attractive is that compressed sensing allows for random
      undersampling of the experimental data, down to less than 5% of the experimental
      data set, with essentially no loss in spectral resolution. We believe that by
      combining powerful resolution with ease of use, compressed sensing can be a
      powerful tool for the analysis and interpretation of ultrafast spectroscopy data.

PMID- 26295895
TI  - Multiresonant Multidimensional Spectroscopy of Surface-Trapped Excitons in PbSe
      Quantum Dots.
AB  - Recent work spectrally isolated and measured the quantum states associated with
      ultrafast relaxation from an initially excited 1S excitonic state to a lower
      energy state that is present in an inadequately capped PbSe quantum dot sample.
      The relaxed state was attributed to a surface-trapped exciton (STE). This letter
      reports the line-narrowed, multiresonant, two-dimensional spectrum of this
      sample. The multidimensional spectrum is unusual because diagonal peaks are
      absent, but there is a strong cross-peak between the 1S and STE transitions.
      Theoretical modeling provided values for the coherent and incoherent dynamics,
      the relative exciton and biexciton transition moments, the Coulombic coupling,
      and the homogeneous and inhomogeneous broadening. This work demonstrates the
      feasibility of using multiresonant methods to probe the quantum state dynamics of
      interface states in nanostructures. 

PMID- 26295896
TI  - Computer Simulation of Water Sorption on Flexible Protein Crystals.
AB  - The first simulation study of water sorption on a flexible protein crystal is
      presented, along with a new computational approach for calculating sorption
      isotherms on compliant materials. The flexible ubiquitin crystal examined in the
      study exhibits appreciable sorption-induced swelling during fluid uptake, similar
      to that reported in experiments on protein powders. A completely rigid ubiquitin
      crystal is also examined to investigate the impact that this swelling behavior
      has on water sorption. The water isotherms for the flexible crystal exhibit Type
      II-like behavior with sorption hysteresis, which is consistent with experimental
      measurements on protein powders. Both of these behaviors, however, are absent in
      the rigid crystal, indicating that modeling flexibility is crucial for predicting
      water sorption behavior in protein systems. Changes in the enthalpy of
      adsorption, specific volume, and internal protein fluctuations that occur during
      sorption in the flexible crystal are also shown to compare favorably with
      experiment. 

PMID- 26295897
TI  - Theoretical Study of Singlet Fission in Oligorylenes.
AB  - Using the time-dependent tuned long-range corrected density functional theory
      method, the feasibility for singlet fission in oligorylenes has been investigated
      within the scope of the diradical character based guideline and of the energy
      level matching conditions for the isolated monomers. It is found that the
      relatively small-size oligorylenes, that is, terrylene and quaterrylene, which
      present intermediate diradical character without significant tetraradical
      character, are possible candidates for energetically efficient singlet fission.
      In relation to this result, we also raise the possibility that the unsettled
      ultrafast dynamics previously observed on quaterrylene is evidence for singlet
      fission. 

PMID- 26295898
TI  - Length Scales for Plasmon Modes in Metal Nanostructures and 2D Spectroscopy in
      the Ultraviolet.

PMID- 26295899
TI  - Four Bases Score a Run: Ab Initio Calculations Quantify a Cooperative Effect of H
      Bonding and pi-Stacking on the Ionization Energy of Adenine in the AATT Tetramer.
AB  - Benchmark calculations of the lowest ionized state of the (A:T)2 (mixed adenine
      thymine) cluster at the geometry taken from the DNA X-ray structure are
      presented. Vertical ionization energies (IEs) computed by the equation-of-motion
      coupled-cluster method with single and double substitutions are reported and
      analyzed. The shift in IE relative to the monomer (A) is -0.7 eV. The performance
      of the widely used B3LYP, omegaB97X-D, and M06-2X functionals with respect to
      their ability to describe energetics and the character (localization versus
      delocalization) of the ionized states is also investigated. The shifts in IEs
      caused by H-bonding and stacking interactions are analyzed in terms of additive
      versus cooperative effects. It is found that the cooperative effect accounts for
      more than 20% of the shift in IE relative to the monomer. The cooperative effect
      and, consequently, the magnitude of the shift are well reproduced by the hybrid
      quantum mechanics/molecular mechanics scheme in which neutral thymine bases are
      represented by point charges. 

PMID- 26295900
TI  - Exploring Protonation and Deprotonation Effects with Auger Electron Spectroscopy.
AB  - Auger electron spectroscopy is demonstrated to be a very efficient tool to probe
      alterations in local chemical environment due to changes in protonation states.
      We show that electronic and geometric structure changes induced by protonation or
      deprotonation are well reflected in Auger spectra through characteristic chemical
      shifts and spectral shape variations. We also present evidence that Auger spectra
      are sensitive to relative concentrations of compounds in different protonation
      states. Special attention is paid to the high kinetic energy spectral regions
      that exhibit remarkable features resulting from core ICD-like transitions in
      normal species and Auger transitions in deprotonated fragments. The latter
      contribution was so far ignored when explaining Auger spectra of species embedded
      in the environment. This contribution should be reconsidered, taking into account
      the recently discovered possibility of ultrafast dissociation of core-ionized
      hydrogen-bonded systems in media. 

PMID- 26295901
TI  - The Level of Particulate Matter on Foliage Depends on the Distance from the
      Source of Emission.
AB  - One of the most dangerous inhaled pollutants is particulate matter (PM). PM in
      inhaled air have a negative impact on human wellbeing and health, and may even
      cause deaths. Where pollutants have been emitted into the outdoor atmosphere, the
      only possible method for cleaning the air is through phytoremediation, a form of
      environmental biotechnology, where plants act as biological filters for
      pollutants. This study compared PM levels on the leaves of Tilia cordata Mill.
      trees growing in locations at increasing distances from the source of the PM
      emission. Significant differences between individual trees growing at a distance
      of between 3 m and 500 m from the road edge were found in: (i) the mass of PM
      that accumulated on leaves (total, surface, in-wax and the three determined size
      fractions) and (ii) the amount of waxes deposited on leaves. 

PMID- 26295902
TI  - The Interrelations Between Internalized Homophobia, Depressive Symptoms, and
      Suicidal Ideation Among Australian Gay Men, Lesbians, and Bisexual Women.
AB  - Internalized homophobia has been linked to depression among gay men, lesbians,
      and bisexuals. Relatively little research has investigated the link between
      internalized homophobia and suicidal thoughts and behaviors. The current research
      investigated the interrelations among internalized homophobia, depressive
      symptoms, and suicidal ideation by testing additive, mediation, and moderation
      models. Self-identified Australian gay men (n = 360), lesbians (n = 444), and
      bisexual women (n = 114) completed the Internalized Homophobia Scale, the Center
      for Epidemiological Studies Depression Scale, and the suicide subscale of the
      General Health Questionnaire. Results supported the additive and partial
      mediation models for gay men and the mediation and moderation models for
      lesbians. None of the models were supported for bisexual women. The findings
      imply that clinicians should focus on reducing internalized homophobia and
      depressive symptoms among gay men and lesbians, and depressive symptoms among
      bisexual women, to reduce suicidal ideation.

PMID- 26295904
TI  - Three-Dimensional Crystalline/Amorphous Co/Co3O4 Core/Shell Nanosheets as
      Efficient Electrocatalysts for the Hydrogen Evolution Reaction.
AB  - Earth-abundant, low-cost electrocatalysts with outstanding catalytic activity in
      the electrochemical hydrogen evolution reaction (HER) are critical in realizing
      the hydrogen economy to lift our future welfare and civilization. Here we report
      that excellent HER activity has been achieved with three-dimensional core/shell
      Co/Co3O4 nanosheets composed of a metallic cobalt core and an amorphous cobalt
      oxide shell. A benchmark HER current density of 10 mA cm(-2) has been achieved at
      an overpotential of ~90 mV in 1 M KOH. The excellent activity is enabled with the
      unique metal/oxide core/shell structure, which allows high electrical
      conductivity in the core and high catalytic activity on the shell. This finding
      may open a door to the design and fabrication of earth-abundant, low-cost metal
      oxide electrocatalysts with satisfactory hydrogen evolution reaction activities. 

PMID- 26295903
TI  - Effects of in Utero Exposure to Arsenic during the Second Half of Gestation on
      Reproductive End Points and Metabolic Parameters in Female CD-1 Mice.
AB  - BACKGROUND: Mice exposed to high levels of arsenic in utero have increased
      susceptibility to tumors such as hepatic and pulmonary carcinomas when they reach
      adulthood. However, the effects of in utero arsenic exposure on general
      physiological functions such as reproduction and metabolism remain unclear.
      OBJECTIVES: We evaluated the effects of in utero exposure to inorganic arsenic at
      the U.S. Environmental Protection Agency (EPA) drinking water standard (10 ppb)
      and at tumor-inducing levels (42.5 ppm) on reproductive end points and metabolic
      parameters when the exposed females reached adulthood. METHODS: Pregnant CD-1
      mice were exposed to sodium arsenite [none (control), 10 ppb, or 42.5 ppm] in
      drinking water from gestational day 10 to birth, the window of organ formation.
      At birth, exposed offspring were fostered to unexposed dams. We examined
      reproductive end points (age at vaginal opening, reproductive hormone levels,
      estrous cyclicity, and fertility) and metabolic parameters (body weight changes,
      hormone levels, body fat content, and glucose tolerance) in the exposed females
      when they reached adulthood. RESULTS: Arsenic-exposed females (10 ppb and 42.5
      ppm) exhibited early onset of vaginal opening. Fertility was not affected when
      females were exposed to the 10-ppb dose. However, the number of litters per
      female was decreased in females exposed to 42.5 ppm of arsenic in utero. In both
      10-ppb and 42.5-ppm groups, arsenic-exposed females had significantly greater
      body weight gain, body fat content, and glucose intolerance. CONCLUSION: Our
      findings revealed unexpected effects of in utero exposure to arsenic: exposure to
      both a human-relevant low dose and a tumor-inducing level led to early onset of
      vaginal opening and to obesity in female CD-1 mice.

PMID- 26295905
TI  - Bisacremines A-D, Dimeric Acremines Produced by a Soil-Derived Acremonium
      persicinum Strain.
AB  - Four dimeric acremines, bisacremines A-D (1-4), with a novel carbon skeleton and
      a new monomer, acremine T (5), were obtained from cultures of the soil-derived
      fungus Acremonium persicinum SC0105. Their structures were characterized by
      analysis of spectroscopic data, ECD/TDDFT computations, and X-ray diffraction.
      Compounds 1 and 2 exhibited weak cytotoxicity against HeLa cells, and 2 also
      showed modest activity against A549 and HepG2 cells. 

PMID- 26295906
TI  - Gelation of Fmoc-diphenylalanine is a first order phase transition.
AB  - We explore the gel transition of the aromatic dipeptide derivative molecule
      fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF). The addition of water to a
      solution of Fmoc-FF in dimethyl sulfoxide (DMSO) results in increased attractions
      leading to self-assembly of Fmoc-FF molecules into a space-filling fibrous
      network. We provide evidence that gel formation is associated with a first order
      phase transition resulting in nucleation and growth of strongly anisotropic
      crystals with high aspect ratios. The strength of attraction between Fmoc-FF
      molecules as a function of water concentration is estimated from long-time self
      diffusion measurements using (1)H NMR diffusion-ordered spectroscopy (DOSY). The
      resulting phase behavior follows that observed for a wide range of other
      crystallizing nanoparticles and small molecules - a result consistent with the
      short-range nature of the intermolecular attractions. Furthermore, we use NMR to
      measure the rate of increase in the fraction of bound Fmoc-FF molecules after
      water is suddenly mixed into the system. We observe a lag time in the formation
      of the new phase indicative of the existence of a free energy barrier to the
      formation of a crystal nucleus of critical size. The application of classical
      nucleation theory for a cylindrical nucleus indicates that one-dimensional
      crystal growth is driven by an imbalance of the surface energies of the ends and
      sides of the fiber. 

PMID- 26295907
TI  - Modelling signaling networks underlying plant defence.
AB  - Transcriptional reprogramming plays a significant role in governing plant
      responses to pathogens. The underlying regulatory networks are complex and
      dynamic, responding to numerous input signals. Most network modelling studies to
      date have used large-scale expression data sets from public repositories but
      defence network models with predictive ability have also been inferred from
      single time series data sets, and sophisticated biological insights generated
      from focused experiments containing multiple network perturbations. Using
      multiple network inference methods, or combining network inference with
      additional data, such as promoter motifs, can enhance the ability of the model to
      predict gene function or regulatory relationships. Network topology can highlight
      key signaling components and provides a systems level understanding of plant
      defence. 

PMID- 26295908
TI  - LC-MS/MS and GC-MS methods in propofol detection: Evaluation of the two
      analytical procedures.
AB  - Propofol is a short-acting hypnotic agent that is commonly used to induce and
      maintain anesthesia. Propofol abuse and its involvement in suicide deaths have
      increased in recent years, especially among healthcare personnel. An example is
      the suicide of a 61-year-old nurse found with a propofol drip in his left arm. We
      describe the postmortem concentration of propofol in various tissues (femoral and
      cardiac blood, bile, urine, brain, and liver) and in the drip. The toxicological
      analyses were performed through two analytical methods, differing in
      derivatization reaction and in instrumentation: silylation for gas chromatograph
      mass spectrometer (GC-MS), as routinely performed in our laboratory for this kind
      of analyses (lower limits of quantification-LLOQ-in urine and blood: 0.3 and
      5ng/ml); for liquid chromatograph-tandem mass spectrometer (LC-MS/MS) an
      innovative azo-coupling derivatization (LLOQ: 0.0004 and 0.1ng/ml). This latter
      produces an azo-derivative (molecular composition: C18H22ON2; molecular weight:
      282Da) highly ionizable in electro-spray ion source, both in negative and
      positive ionizations. These two methods were compared to evaluate the
      effectiveness of this new LC-MS/MS analysis. An acidic hydrolysis (HCl 6N, 100
      degrees C, and 1h) was performed for the biological samples (1ml or 1g)
      irrespective of the analytical method applied. The drip content was extracted
      adding phosphate buffer (pH 8) and a dichloromethane/ethylacetate 8:2 (v:v)
      mixture. Derivatization steps were: silylation with N,O
      bis(trimethylsilyl)trifluoroacetamide (BSTFA)+tetramethylammonium hydroxide
      (TMAH) for GC-MS; regarding LC-MS/MS, azo-coupling reaction with the aryl
      diazonium salt (0-5 degrees C, and 30min). The analyses were achieved in selected
      ion monitoring for GC-MS (m/z, 235,250,73 propofol"; m/z, 252,267,27 propofol
      d17) and in multiple reaction monitoring ([M-H](-): m/z 283->241,77, azo
      propofol; m/z 299->251,77, azo-propofol-d17) for LC-MS/MS. Autopsy showed no
      significant findings. Propofol concentrations were (LC-MS/MS vs GC-MS,
      respectively): 15.1 vs 14.5mg/ml, drip content; 7.11 vs 6.07MUg/ml, cardiac
      blood; 9.50 vs 7.19MUg/ml, femoral blood; 0.64 vs 1.07MUg/ml, bile; 0.042 vs
      0.051MUg/ml urine; 4.93 vs 5.89MUg/g, brain; and 7.88 vs 6.80MUg/g, liver. These
      values are comparable with the ones described in literature for death by acute
      propofol intoxication; the drip content is compatible with a diluted formulation
      of propofol available in Italy (20mg/ml injectable emulsion). The comparison
      shows an excellent fitting of the data (R(2): 0.9362). Toxicological results
      proved the cause of death as acute propofol intoxication. Furthermore, the new LC
      MS/MS method showed an excellent effectiveness and reliability when compared to
      the routinely used GC-MS method. 

PMID- 26295909
TI  - In vivo detection of the new psychoactive substance AM-694 and its metabolites.
AB  - AM-694 or 1-(5-fluoropentyl)-3-(2-iodobenzoyl)indole is a synthetic cannabinoid
      that acts as a selective and a powerful agonist for CB1 receptor, inducing
      cannabinoid-like effects (euphoria, sedation, hallucinations and anxiety). Its
      spread, like for other synthetic cannabinoids, has increased in recent years and
      many web sources freely supply these kinds of new drugs. It can be taken by
      smoking or through oral consumption. A 25-years-old man was hospitalized at the
      local hospital following a major trauma after ingestion of alcohol and an unknown
      pill. Urine and blood samples were sent to our Forensic Toxicology Division to
      investigate on possible substance abuse. A general unknown screening of
      biological samples, extracted by liquid-liquid extraction (ethylacetate and
      dichloromethane) in basic, acidic and neutral conditions, was achieved to verify
      the presence of drugs of abuse and/or their metabolites, both in gas
      chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). For the quantification of AM-694, urine was extracted by
      solid phase extraction (SPE) on a Bond Elut Certify cartridge; an acidic
      hydrolysis (HCl 30%, 95 degrees C, 60min) was necessary before liquid-liquid
      extraction of metabolites. For the detection of benzodiazepines and their
      metabolites, an enzymatic hydrolysis was applied (beta-glucuronidase, pH 4.5, 50
      degrees C, 18h). Quantification of AM-694 (internal standard AM-2201), midazolam
      and alpha-hydroxymidazolam (internal standard halazepam) were performed by LC
      MS/MS analysis in multiple reaction monitoring ([M+H](+): m/z 436->190, 272, AM
      694; m/z 360->155, 127, AM-2201; m/z 326->291, 223, midazolam; m/z 342->168, 203,
      alpha-hydroxymidazolam; m/z 353->241, 222, halazepam). The general unknown
      screening revealed the presence of AM-694 (urine sample) and benzodiazepines
      (urine and blood). The concentration of AM-694, obtained by LC-MS/MS, was
      0.084MUg/L. Midazolam and alpha-hydroxymidazolam were detected in urine (0.97 and
      74.58MUg/L, respectively) and in blood (34.84 and 23.15MUg/L, respectively).
      Qualitative information about the AM-694 metabolites was obtained by LC-MS/MS in
      selected-ion monitoring for the putative [M+H](+) ions: m/z 448, carboxylated
      metabolite; m/z 434, defluorinated metabolite; quantification was not possible
      since reference standards are not available. Our report is the first case of
      detection of AM-694 and its metabolites in human biological fluids in Italy. For
      this reason, this case constitutes a first worrisome alarm about the spread of
      this substance. 

PMID- 26295910
TI  - Assessment of the stability of mephedrone in ante-mortem and post-mortem blood
      specimens.
AB  - AIMS: The aim of this work is to test the stability of mephedrone added to whole
      blood collected from alive and dead mephedrone free-users and stored at three
      different temperatures (-20, +4 and +20 degrees C) with and without preservatives
      up to 6 months, trying to establish the best storage condition in order to reduce
      possible analyte loss/degradation during the storage period. MATERIALS AND
      METHODS: Different sources of blood were obtained as follow: 10 samples of blood
      came from 10 alive mephedrone free-users (mean age 34+/-15.8 years old) (Group
      1), whereas 10 post mortem blood samples were obtained from 10 cadavers, in which
      the post mortem interval was between 24 and 36h (Group 2). The cause of death in
      post mortem cases (mean age 45+/-14.2 years old) was not drug related. Pools of
      blood were spiked with mephedrone at the concentration of 1mg/L and 1mL aliquots
      were transferred in 2mL Eppendorf capped tubes with and without preservatives as
      follow: with ethylenediaminetetraacetic acid (EDTA) 3%; with sodium
      fluoride/potassium oxalate (NaF/KOx) 1.67%/0.2%, respectively; without
      preservatives. All samples were stored at three different temperatures: -20
      degrees C, 4 degrees C and 20 degrees C and extracted and analyzed in duplicate
      by GC-MS according to a previously published method by Dickson et al., every
      other day during the first month and then weekly up to 6 months. RESULTS AND
      CONCLUSIONS: our study allow us to affirm that -20 degrees C is the best storage
      temperature for mephedrone stability in ante-mortem and post-mortem blood samples
      in comparison to the other two tested temperatures (+4 and +20 degrees C),
      showing higher values in both groups in samples stored with and without
      preservatives (p<0.0001). The comparison of Group 1 (samples coming from alive
      subjects) and Group 2 (post-mortem samples) highlights a better stability of
      mephedrone in Group 1 (p<0.001) at all tested storage conditions. Finally, the
      analysis of blood specimens stored with and without preservatives in both groups
      suggests that specimens stored with NaF/KOx maintain mephedrone stability better
      than those stored with EDTA (p<0.001) and those stored without preservatives
      (p<0.0001), therefore, we strongly recommend in order to maintain the highest
      mephedrone stability in blood, to store specimens at -20 degrees C adding NaF/KOx
      as preservative.

PMID- 26295911
TI  - Detection of illicit drugs in oral fluid from drivers as biomarker for drugs in
      blood.
AB  - AIM: To assess whether analysis of oral fluid can be used to identify individual
      drivers with drug concentrations in blood above 25ng/mL for amphetamine and
      methamphetamine, 10ng/mL for cocaine and 1.0ng/mL for tetrahydrocannabinol (THC),
      which are the cut-off concentrations used in the European DRUID Project, by
      calculating the diagnostic accuracies when using the analytical cut-off
      concentrations in oral fluid as well as for the optimal cut-off concentrations.
      METHODS: Paired samples of whole blood and oral fluid collected with the Statsure
      SalivaSampler were obtained from 4080 drivers in four European countries and
      analysed for amphetamine, methamphetamine, cocaine and THC using GC-MS or LC-MS.
      The vast majority (89%) were random drivers not suspected of drug-impaired
      driving. Receiver-Operating Characteristic analysis was used to evaluate the
      analytical results. RESULTS: The prevalence of drug findings above the cut-off
      concentrations in blood was 1.3% for amphetamine, 1.0% for methamphetamine, 0.6%
      for cocaine and 1.3% for THC. The cut-off concentrations in oral fluid that gave
      the highest diagnostic accuracy were for amphetamine 130ng/mL (accuracy 99.8%),
      methamphetamine 280ng/mL (accuracy 99.9%), cocaine 570ng/mL (accuracy 99.6%), and
      THC 38ng/mL (accuracy 98.3%). The proportion of false positives were 0.2%, 0.1%,
      0.1% and 0.9%; and the proportion of false negatives were 0.1%, 0.0%, 0.3% and
      0.8%, respectively, when using those cut-offs. The positive predictive values
      were 87.9%, 92.9%, 84.6% and 35.7% for amphetamine, methamphetamine, cocaine and
      THC, respectively. CONCLUSIONS: Analysis of concentrations of illicit drugs in
      oral fluid could not be used to accurately identify drivers with drugs
      concentrations above the selected cut-offs in blood in a cohort of drivers with
      low prevalence of drugs.

PMID- 26295912
TI  - Sensitivity and specificity of intrathecal fluorescein and white light excitation
      for detecting intraoperative cerebrospinal fluid leak in endoscopic skull base
      surgery: a prospective study.
AB  - OBJECTIVE: The intraoperative detection of CSF leaks during endonasal endoscopic
      skull base surgery is critical to preventing postoperative CSF leaks. Intrathecal
      fluorescein (ITF) has been used at varying doses to aid in the detection of
      intraoperative CSF leaks. However, the sensitivity and specificity of ITF at
      certain dosages is unknown. METHODS: A prospective database of all endoscopic
      endonasal procedures was reviewed. All patients received 25 mg ITF diluted in 10
      ml CSF and were pretreated with dexamethasone and Benadryl. Immediately after
      surgery, the operating surgeon prospectively noted if there was an intraoperative
      CSF leak and fluorescein was identified. The sensitivity, specificity, and
      positive and negative predictive power of ITF for detecting intraoperative CSF
      leak were calculated. Factors correlating with postoperative CSF leak were
      determined. RESULTS: Of 419 patients, 35.8% of patients did not show a CSF leak.
      Fluorescein-tinted CSF (true positive) was noted in 59.7% of patients and 0 false
      positives were encountered. CSF without fluorescein staining (false negative) was
      noted in 4.5% of patients. The sensitivity and specificity of ITF were 92.9% and
      100%, respectively. The negative and positive predictive values were 88.8% and
      100%, respectively. Postoperative CSF leaks only occurred in true positives at a
      rate of 2.8%. CONCLUSIONS: ITF is extremely specific and very sensitive for
      detecting intraoperative CSF leaks. Although false negatives can occur, these
      patients do not appear to be at risk for postoperative CSF leak. The use of ITF
      may help surgeons prevent postoperative CSF leaks by intraoperatively detecting
      and confirming a watertight repair.

PMID- 26295913
TI  - Validation of a noninvasive test routinely used in otology for the diagnosis of
      cerebrospinal fluid shunt malfunction in patients with normal pressure
      hydrocephalus.
AB  - OBJECTIVE: Ventriculoperitoneal shunting is the first-line treatment for normal
      pressure hydrocephalus. Noninvasive auditory tests based on recorded otoacoustic
      emissions were assessed, as currently used for universal neonatal hearing
      screenings, for the diagnosis of cerebrospinal fluid shunt malfunction. The test
      was designed based on previous works, which demonstrated that an intracranial
      pressure change induces a proportional, characteristic, otoacoustic-emission
      phase shift. METHODS: Forty-four patients with normal pressure hydrocephalus (23
      idiopathic and 21 secondary cases) were included in this prospective
      observational study. The male:female sex ratio was 1.44, the age range was 21-87
      years (mean age 64.3 years), and the range of the follow-up period was 1-3 years
      (mean 20 months). Patients were implanted with a Sophy SU8 adjustable-pressure
      valve as the ventriculoperitoneal shunt. The phase shifts of otoacoustic
      emissions in response to body tilt were measured preoperatively, immediately
      postoperatively, and at 3-6 months, 7-15 months, 16-24 months, and more than 24
      months postoperatively. Three groups were enrolled: Group 1, 19 patients who
      required no valve opening-pressure adjustment; Group 2, 18 patients who required
      valve opening-pressure adjustments; and Group 3, 7 patients who required valve
      replacement. RESULTS: In Group 1, phase shift, which was positive before surgery,
      became steadily negative after surgery and during the follow-up. In Group 2,
      phase shift, which was positive before surgery, became negative immediately after
      surgery and increasingly negative after a decrease in the valve-opening pressure.
      In Group 3, phase shift was positive in 6 cases and slightly negative in 1 case
      before revision, but after revision phase shift became significantly negative in
      all cases. CONCLUSIONS: Otoacoustic emissions noninvasively reflect cerebrospinal
      fluid shunt function and are impacted by valve-opening pressure adjustments.
      Otoacoustic emissions consistently diagnosed shunt malfunction and predicted the
      need for surgical revision. The authors' diagnostic test, which can be repeated
      without risk or discomfort by an unskilled operator, may address the crucial need
      of detecting valve dysfunction in patients with poor clinical outcome after shunt
      surgery.

PMID- 26295914
TI  - Magnetic resonance imaging of the subthalamic nucleus for deep brain stimulation.
AB  - The subthalamic nucleus (STN) is one of the most important stereotactic targets
      in neurosurgery, and its accurate imaging is crucial. With improving MRI
      sequences there is impetus for direct targeting of the STN. High-quality,
      distortion-free images are paramount. Image reconstruction techniques appear to
      show the greatest promise in balancing the issue of geometrical distortion and
      STN edge detection. Existing spin echo- and susceptibility-based MRI sequences
      are compared with new image reconstruction methods. Quantitative susceptibility
      mapping is the most promising technique for stereotactic imaging of the STN. 

PMID- 26295916
TI  - Failed microvascular decompression surgery for hemifacial spasm due to persistent
      neurovascular compression: an analysis of reoperations.
AB  - OBJECT Microvascular decompression (MVD) surgery for hemifacial spasm (HFS) is
      potentially curative. The findings at repeat MVD in patients with persistent or
      recurrent HFS were analyzed with the aim to identify factors that may improve
      surgical outcomes. METHODS Intraoperative findings were determined from review of
      dictated operative reports and operative diagrams for patients who underwent
      repeat MVD after prior surgery elsewhere. Clinical follow-up was obtained from
      the hospital and clinic records, as well as telephone questionnaires. RESULTS
      Among 845 patients who underwent MVD performed by the senior author, 12 had been
      referred after prior MVD for HFS performed elsewhere. Following repeat MVD, all
      patients improved and complete spasm resolution was described by 11 of 12
      patients after a mean follow-up of 91 +/- 55 months (range 28-193). Complications
      were limited to 1 patient with aggravation of preexisting hearing loss and mild
      facial weakness and 1 patient with aseptic meningitis without sequelae.
      Significant factors that may have contributed to the failure of the first surgery
      included retromastoid craniectomies that did not extend laterally to the sigmoid
      sinus or inferiorly to the posterior fossa floor in 11 of 12 patients and a prior
      surgical approach that focused on the cisternal portion of the facial nerve in 9
      of 12 patients. In all cases, significant persistent neurovascular compression
      (NVC) was evident and alleviated more proximally on the facial root exit zone
      (fREZ). CONCLUSIONS Most HFS patients will achieve spasm relief with thorough
      alleviation of NVC of the fREZ, which extends from the pontomedullary sulcus root
      exit point to the Obersteiner-Redlich transition zone. 

PMID- 26295917
TI  - A case of secondary somatosensory epilepsy with a left deep parietal opercular
      lesion: successful tumor resection using a transsubcentral gyral approach during
      awake surgery.
AB  - Few studies have examined the clinical characteristics of patients with lesions
      in the deep parietal operculum facing the sylvian fissure, the region recognized
      as the secondary somatosensory area (SII). Moreover, surgical approaches in this
      region are challenging. In this paper the authors report on a patient presenting
      with SII epilepsy with a tumor in the left deep parietal operculum. The patient
      was a 24-year-old man who suffered daily partial seizures with extremely
      uncomfortable dysesthesia and/or occasional pain on his right side. MRI revealed
      a tumor in the medial aspect of the anterior transverse parietal gyrus,
      surrounding the posterior insular point. Long-term video electroencephalography
      monitoring with scalp electrodes failed to show relevant changes to seizures.
      Resection with cortical and subcortical mapping under awake conditions was
      performed. A negative response to stimulation was observed at the subcentral
      gyrus during language and somatosensory tasks; thus, the transcortical approach
      (specifically, a transsubcentral gyral approach) was used through this region.
      Subcortical stimulation at the medial aspect of the anterior parietal gyrus and
      the posterior insula around the posterior insular point elicited strong
      dysesthesia and pain in his right side, similar to manifestation of his seizure.
      The tumor was completely removed and pathologically diagnosed as pleomorphic
      xanthoastrocytoma. His epilepsy disappeared without neurological deterioration
      postoperatively. In this case study, 3 points are clinically significant. First,
      the clinical manifestation of this case was quite rare, although still
      representative of SII epilepsy. Second, the location of the lesion made surgical
      removal challenging, and the transsubcentral gyral approach was useful when
      intraoperative mapping was performed during awake surgery. Third, intraoperative
      mapping demonstrated that the patient experienced pain with electrical
      stimulation around the posterior insular point. Thus, this report demonstrated
      the safe and effective use of the transsubcentral gyral approach during awake
      surgery to resect deep parietal opercular lesions, clarified electrophysiological
      characteristics in the SII area, and achieved successful tumor resection with
      good control of epilepsy. 

PMID- 26295918
TI  - A case of dural arteriovenous fistula draining to the diploic vein presenting
      with intracerebral hemorrhage.
AB  - The authors report an unusual case of a dural arteriovenous fistula (dAVF)
      draining only to the diploic vein and causing intracerebral hemorrhage. A 62-year
      old woman presented with disturbance of consciousness and left hemiparesis. Brain
      CT scanning on admission showed a right frontal subcortical hemorrhage. Digital
      subtraction angiography revealed an arteriovenous shunt located in the region
      around the pterion, which connected the frontal branch of the right middle
      meningeal artery with the anterior temporal diploic vein and drained into
      cortical veins in a retrograde manner through the falcine vein. The dAVF was
      successfully obliterated by percutaneous transarterial embolization with N-butyl
      2-cyanoacrylate. The mechanism of retrograde cortical venous reflux causing
      intracerebral hemorrhage is discussed. 

PMID- 26295915
TI  - Structural and biochemical abnormalities in the absence of acute deficits in mild
      primary blast-induced head trauma.
AB  - OBJECTIVE: Blast-induced neurotrauma (BINT), if not fatal, is nonetheless
      potentially crippling. It can produce a wide array of acute symptoms in moderate
      to-severe exposures, but mild BINT (mBINT) is characterized by the distinct
      absence of acute clinical abnormalities. The lack of observable indications for
      mBINT is particularly alarming, as these injuries have been linked to severe long
      term psychiatric and degenerative neurological dysfunction. Although the long
      term sequelae of BINT are extensively documented, the underlying mechanisms of
      injury remain poorly understood, impeding the development of diagnostic and
      treatment strategies. The primary goal of this research was to recapitulate
      primary mBINT in rodents in order to facilitate well-controlled, long-term
      investigations of blast-induced pathological neurological sequelae and identify
      potential mechanisms by which ongoing damage may occur postinjury. METHODS: A
      validated, open-ended shock tube model was used to deliver blast overpressure
      (150 kPa) to anesthetized rats with body shielding and head fixation, simulating
      the protective effects of military-grade body armor and isolating a shock wave
      injury from confounding systemic injury responses, head acceleration, and other
      elements of explosive events. Evans Blue-labeled albumin was used to visualize
      blood-brain barrier (BBB) compromise at 4 hours postinjury. Iba1 staining was
      used to visualize activated microglia and infiltrating macrophages in areas of
      peak BBB compromise. Acrolein, a potent posttraumatic neurotoxin, was quantified
      in brain tissue by immunoblotting and in urine through liquid chromatography with
      tandem mass spectrometry at 1, 2, 3, and 5 days postinjury. Locomotor behavior,
      motor performance, and short-term memory were assessed with open field, rotarod,
      and novel object recognition (NOR) paradigms at 24 and 48 hours after the blast.
      RESULTS: Average speed, maximum speed, and distance traveled in an open-field
      exploration paradigm did not show significant differences in performance between
      sham-injured and mBINT rats. Likewise, rats with mBINT did not exhibit deficits
      in maximum revolutions per minute or total run time in a rotarod paradigm. Short
      term memory was also unaffected by mBINT in an NOR paradigm. Despite lacking
      observable motor or cognitive deficits in the acute term, blast-injured rats
      displayed brain acrolein levels that were significantly elevated for at least 5
      days, and acrolein's glutathione-reduced metabolite, 3-HPMA, was present in urine
      for 2 days after injury. Additionally, mBINT brain tissue demonstrated BBB damage
      4 hours postinjury and colocalized neuroinflammatory changes 24 hours postinjury.
      CONCLUSIONS: This model highlights mBINT's potential for underlying detrimental
      physical and biochemical alterations despite the lack of apparent acute symptoms
      and, by recapitulating the human condition, represents an avenue for further
      examining the pathophysiology of mBINT. The sustained upregulation of acrolein
      for days after injury suggests that acrolein may be an upstream player
      potentiating ongoing postinjury damage and neuroinflammation. Ultimately,
      continued research with this model may lead to diagnostic and treatment
      mechanisms capable of preventing or reducing the severity of long-term
      neurological dysfunction following mBINT.

PMID- 26295919
TI  - Default mode network connectivity in patients with idiopathic normal pressure
      hydrocephalus.
AB  - OBJECTIVE: Idiopathic normal pressure hydrocephalus (iNPH) is a neurological
      disorder characterized by gait disturbance, cognitive impairment, and
      incontinence. It is unclear whether the pathophysiology of iNPH is associated
      with alterations in the default mode network (DMN). The authors investigated
      alterations in the DMN of patients with iNPH and sought to determine whether a
      relationship exists between the resting-state functional connectivity of the DMN
      and a patient's clinical symptoms. METHODS: Resting-state functional MRI (rs
      fMRI) was performed in 16 preoperative patients with iNPH and 15 neurologically
      healthy control subjects of a similar age. Independent component and dual
      regression analyses were used to quantify DMN connectivity. The patients'
      clinical symptoms were rated according to the iNPH grading scale (iNPHGS). Each
      of their specific clinical symptoms were rated according to the cognitive, gait,
      and urinary continence domains of iNPHGS, and neurocognitive status was assessed
      using the Mini-Mental State Examination, Frontal Assessment Battery (FAB), and
      Trail Making Test Part A. The strength of DMN connectivity was compared between
      patients and controls, and the correlation between DMN connectivity and iNPHGS
      was examined using both region of interest (ROI)-based analysis and voxel-based
      analysis. The correlation between DMN connectivity and each of the specific
      clinical symptoms, as well as neurocognitive status, was examined using voxel
      based analysis. RESULTS: Both ROI-based and voxel-based analyses revealed reduced
      DMN connectivity in patients with iNPH. ROI-based analysis showed increased DMN
      connectivity with worsening clinical symptoms of iNPH. Consistently, voxel-based
      analyses revealed that DMN connectivity correlated positively with the iNPHGS
      score, as well as the cognitive and urinary continence domain scores, and
      negatively with the FAB score. The significant peak in correlation in each case
      was localized to the precuneus. CONCLUSIONS: This is the first study to establish
      alterations in the DMN of patients with iNPH. DMN connectivity may be a useful
      indicator of the severity of clinical symptoms in patients with iNPH.

PMID- 26295920
TI  - Outbreaks, Middle East respiratory syndrome and sepsis in emergency care.

PMID- 26295921
TI  - Research in prehospital emergency medicine: comparison by geographic origin of
      publications.

PMID- 26295922
TI  - Difficulties to study the geographical origin of a publication.

PMID- 26295923
TI  - A Bayesian joint model of menstrual cycle length and fecundity.
AB  - Menstrual cycle length (MCL) has been shown to play an important role in couple
      fecundity, which is the biologic capacity for reproduction irrespective of
      pregnancy intentions. However, a comprehensive assessment of its role requires a
      fecundity model that accounts for male and female attributes and the couple's
      intercourse pattern relative to the ovulation day. To this end, we employ a
      Bayesian joint model for MCL and pregnancy. MCLs follow a scale multiplied
      (accelerated) mixture model with Gaussian and Gumbel components; the pregnancy
      model includes MCL as a covariate and computes the cycle-specific probability of
      pregnancy in a menstrual cycle conditional on the pattern of intercourse and no
      previous fertilization. Day-specific fertilization probability is modeled using
      natural, cubic splines. We analyze data from the Longitudinal Investigation of
      Fertility and the Environment Study (the LIFE Study), a couple based prospective
      pregnancy study, and find a statistically significant quadratic relation between
      fecundity and menstrual cycle length, after adjustment for intercourse pattern
      and other attributes, including male semen quality, both partner's age, and
      active smoking status (determined by baseline cotinine level 100 ng/mL). We
      compare results to those produced by a more basic model and show the advantages
      of a more comprehensive approach.

PMID- 26295924
TI  - Collaborative learning framework for online stakeholder engagement.
AB  - BACKGROUND: Public and stakeholder engagement can improve the quality of both
      research and policy decision making. However, such engagement poses significant
      methodological challenges in terms of collecting and analysing input from large,
      diverse groups. OBJECTIVE: To explain how online approaches can facilitate
      iterative stakeholder engagement, to describe how input from large and diverse
      stakeholder groups can be analysed and to propose a collaborative learning
      framework (CLF) to interpret stakeholder engagement results. METHODS: We use 'A
      National Conversation on Reducing the Burden of Suicide in the United States' as
      a case study of online stakeholder engagement and employ a Bayesian data
      modelling approach to develop a CLF. RESULTS: Our data modelling results
      identified six distinct stakeholder clusters that varied in the degree of
      individual articulation and group agreement and exhibited one of the three
      learning styles: learning towards consensus, learning by contrast and groupthink.
      Learning by contrast was the most common, or dominant, learning style in this
      study. CONCLUSION: Study results were used to develop a CLF, which helps explore
      multitude of stakeholder perspectives; identifies clusters of participants with
      similar shifts in beliefs; offers an empirically derived indicator of engagement
      quality; and helps determine the dominant learning style. The ability to detect
      learning by contrast helps illustrate differences in stakeholder perspectives,
      which may help policymakers, including Patient-Centered Outcomes Research
      Institute, make better decisions by soliciting and incorporating input from
      patients, caregivers, health-care providers and researchers. Study results have
      important implications for soliciting and incorporating input from stakeholders
      with different interests and perspectives.

PMID- 26295925
TI  - A family of 12-azametallacrown-4 structural motif with heterometallic Mn(III) -Ln
      Mn(III) -Ln (Ln=Dy, Er, Yb, Tb, Y) alternate arrangement and single-molecule
      magnet behavior.
AB  - Mixed 3d-4f 12-azametallacrown-4 complexes, [Mn2 Ln2 (OH)2 (hppt)4 (OAc)2 (DMF)2
      ]?2 DMF?H2 O [Ln=Dy (1), Er (2), Yb (3), Tb (4) and Y (5), H2 hppt=3-(2
      hydroxyphenyl)-5-(pyrazin-2-yl)-1,2,4-triazole)], were synthesized by reactions
      of H2 hppt with Mn(OAc)2 ?4 H2 O and Ln(NO3 )3 ?6 H2 O. This is the first 3d-4f
      azametallacrown family to incorporate Ln ions into the ring sets. These
      isostructural complexes exhibit alternating arrangements of two Mn and two Ln
      ions in the rings with each pair of metal centers bound by an N?N group and MU2 
      O bridging. Magnetic measurements revealed dominant antiferromagnetic
      interactions between metal centers, and frequency-dependent out-of-phase (${?chi
      {^?prime}{^?prime}_{?rm{M}} }$) signals below 4 K suggest slow relaxation of
      magnetization. 

PMID- 26295926
TI  - Development of a physiologically based pharmacokinetic/pharmacodynamic model to
      identify mechanisms contributing to entacapone low bioavailability.
AB  - Entacapone is an inhibitor of catechol-O-methyltransferase (COMT) and is being
      used to extend the therapeutic effect of levodopa in patients with advanced and
      fluctuating Parkinson's disease. Entacapone has low and variable oral
      bioavailability and the underlying mechanism(s) for this behavior have not been
      studied. To explain such behavior and to characterize the dynamic changes in the
      metabolism of entacapone, a physiologically based pharmacokinetic/pharmacodynamic
      (PBPK/PD) model was developed integrating in silico, in vitro and in vivo
      pharmacokinetic data. The model was developed and verified in healthy volunteers
      and subsequently expanded to predict the pharmacokinetic parameters of entacapone
      phosphate, a prodrug of entacapone, and to assess the impact of hepatic
      impairment on the pharmacokinetics of entacapone. Low and inter-individual
      variability in bioavailability could be attributed to the extensive first-pass
      metabolism by UGTs in the liver and, to a lesser extent, the small intestine. The
      predictive performance of this model was acceptable with predicted Cmax , AUC and
      PD parameters lying within 20% of the observed data. The model indicates that the
      low bioavailability could be attributed to the extensive first-pass effect of
      entacapone.

PMID- 26295927
TI  - Estimating age from the pubic symphysis: A new component-based system.
AB  - The os pubis is one of the most widely used areas of the skeleton for age
      estimation. Current pubic symphyseal aging methods for adults combine the
      morphology associated with the developmental changes that occur into the mid-30s
      with the degenerative changes that span the latter portion of the age spectrum.
      The most popular methods are phase-based; however, the definitions currently used
      to estimate age intervals may not be adequately defined and/or accurately
      understood by burgeoning researchers and seasoned practitioners alike. This study
      identifies patterns of growth and maturation in the pubic symphysis to derive
      more precise age estimates for individuals under 40 years of age. Emphasis is
      placed on young adults to provide more informative descriptions of epiphyseal
      changes associated with the final phases of skeletal maturation before
      degeneration commences. This study investigated macroscopic changes in
      forensically relevant modern U.S. samples of known age, sex, and ancestry from
      the Maricopa County Forensic Science Center in Phoenix, Arizona as well as
      donated individuals from the William M. Bass Forensic and Donated Collections at
      the University of Tennessee, Knoxville (n=237). Age-related traits at locations
      with ontogenetic and biomechanical relevance were broken into components and
      scored. The components included the pubic tubercle, the superior apex of the
      face, the ventral and dorsal demifaces, and the ventral and dorsal symphyseal
      margins. Transition analysis was applied to elucidate the transition ages between
      the morphological states of each component. The categorical scores and transition
      analysis ages were subjected to multinomial logistic regression and decision tree
      analysis to derive accurate age interval estimates. Results of these analyses
      were used to construct a decision tree-style flow chart for practitioner use.
      High inter-rater agreement of the individual component traits (linear weighted
      kappa values >=0.665 for all traits in the decision tree) indicates that the
      method offers unambiguous scoring for age-related changes of the pubic symphysis.
      Validation of the flow chart on a sample of 47 individuals provided by the
      Montana State Crime Lab yielded 94% accuracy overall, indicating that the method
      has the potential to deliver precise and accurate age estimates of individuals
      prior to the onset of advanced degenerative changes. A pubic symphysis that
      exhibits epiphyseal changes and/or billowing is suitable for this method; a pubic
      symphysis that exhibits degenerative changes (i.e. porosity and/or rim erosion)
      is not suitable. 

PMID- 26295928
TI  - Unsolved homicides in Sweden: A population-based study of 264 homicides.
AB  - The clearance rates for homicides have decreased internationally. This
      retrospective population-based study of all Swedish homicide incidents between
      2007 and 2009 (n=264) aims to investigate factors associated with solvability in
      homicides. Victims were identified in an autopsy registry and offenders in a
      criminal-conviction registry. Autopsy reports, police files, court verdicts and
      criminal records were systematically collected and linked. The clearance rate was
      86.4% (n=228), and almost three quarters of cases (71.9%) were solved within the
      first week. Nine factors were significantly associated with the case status;
      however, only four factors remained significant in the multivariate logistic
      regression model. Cases were more likely to be solved if there was an eyewitness
      and if the victim was intoxicated with alcohol. Moreover, cases were less likely
      to be solved if the victim had a criminal record in the past five years and was
      killed by a firearm. In the final model, a Cox proportional-hazards model, where
      time to arrest was taken into account, only alcohol intoxication were positively
      and firearms negatively significantly associated with clearance status. The study
      concludes that cases involving these factors should be granted extra, intensive
      and lasting resources. 

PMID- 26295929
TI  - Facial soft tissue thicknesses: Noise, signal, and P.
AB  - Facial soft tissue thicknesses (FSTTs) hold an important role in craniofacial
      identification, forming the underlying quantitative basis of craniofacial
      superimposition and facial approximation methods. It is, therefore, important
      that patterns in FSTTs be correctly described and interpreted. In prior FSTT
      literature, small statistically significant differences have almost universally
      been overemphasized and misinterpreted to reflect sex and ancestry effects when
      they instead largely encode nuisance statistical noise. Here we examine FSTT data
      and give an overview of why P-values do not mean everything. Scientific
      inference, not mechanical evaluation of P, should be awarded higher priority and
      should form the basis of FSTT analysis. This hinges upon tempered consideration
      of many factors in addition to P, e.g., study design, sampling, measurement
      errors, repeatability, reproducibility, and effect size. While there are multiple
      lessons to be had, the underlying message is foundational: know enough statistics
      to avoid misinterpreting background noise for real biological effects. 

PMID- 26295930
TI  - Utilizing AFIS searching tools to reduce errors in fingerprint casework.
AB  - Fifty-six (56) adjudicated, property crime cases involving fingerprint evidence
      were reviewed using a case-specific AFIS database tool. This tool allowed
      fingerprint experts to search latent prints in the cases against a database of
      friction ridge exemplars limited to only the individuals specific to that
      particular case. We utilized three different methods to encode and search the
      latent prints: automatic feature extraction, manual encoding performed by a
      student intern, and manual encoding performed by a fingerprint expert.
      Performance in the study was strongest when the encoding was conducted by the
      fingerprint expert. The results of the study showed that while the AFIS tools
      failed to locate all of the identifications originally reported by the initial
      fingerprint expert that worked the case, the AFIS tools helped to identify 7
      additional latent prints that were not reported by the initial fingerprint
      expert. We conclude that this technology, when combined with fingerprint
      expertise, will reduce the number of instances where an erroneous exclusion could
      occur, increase the efficiency of a fingerprint unit, and be a useful tool for
      reviewing active or cold cases for missed opportunities to report
      identifications. 

PMID- 26295931
TI  - New incompatibilities uncovered using the Promega DNA IQTM chemistry.
AB  - Over the years, the Promega DNA IQTM System was proven an effective technology
      for the production of clean DNA from a wide variety of casework specimens. The
      capture of DNA using the DNA IQTM paramagnetic beads, however, was shown to be
      affected by a few specific chemicals that could be present on exhibits submitted
      to the laboratory. In this study, various blood and latent fingerprint
      enhancement reagents/methods, marker pens and adhesive tapes, applied at the
      crime scene or in the forensic laboratory on casework exhibits or used to collect
      biological material, were tested for their compatibility with the DNA IQTM
      technology. Although no impact on DNA recovery was observed for most reagents,
      the MAGNATM Jet Black fingerprint powder and three 3M Scotch((r)) adhesive tapes
      were shown to severely or completely inhibit DNA binding onto the DNA IQTM beads.
      The effect of MAGNATM Jet Black on DNA recovery could be counteracted by
      separating the magnetic powder from the lysates by centrifugation or filtration,
      prior to DNA extraction. High quality STR profiles were obtained from samples
      subjected to MAGNATM Jet Black suggesting it does not impact DNA integrity. 

PMID- 26295932
TI  - The power within: The experimental manipulation of power interacts with trait BDD
      symptoms to predict interoceptive accuracy.
AB  - BACKGROUND AND OBJECTIVES: This study tested whether relatively low levels of
      interoceptive accuracy (IAcc) are associated with body dysmorphic disorder (BDD)
      symptoms. Additionally, given research indicating that power attunes individuals
      to their internal states, we sought to determine if state interoceptive accuracy
      could be improved through an experimental manipulation of power.. METHOD:
      Undergraduate women (N = 101) completed a baseline measure of interoceptive
      accuracy and then were randomized to a power or control condition. Participants
      were primed with power or a neutral control topic and then completed a post
      manipulation measure of state IAcc. Trait BDD symptoms were assessed with a self
      report measure. RESULTS: Controlling for baseline IAcc, within the control
      condition, there was a significant inverse relationship between trait BDD
      symptoms and interoceptive accuracy. Continuing to control for baseline IAcc,
      within the power condition, there was not a significant relationship between
      trait BDD symptoms and IAcc, suggesting that power may have attenuated this
      relationship. At high levels of BDD symptomology, there was also a significant
      simple effect of experimental condition, such that participants in the power (vs.
      control) condition had better interoceptive accuracy. These results provide
      initial evidence that power may positively impact interoceptive accuracy among
      those with high levels of BDD symptoms.. LIMITATIONS: This cross-sectional study
      utilized a demographically homogenous sample of women that reflected a broad
      range of symptoms; thus, although there were a number of participants reporting
      elevated BDD symptoms, these findings might not generalize to other populations
      or clinical samples. CONCLUSIONS: This study provides the first direct test of
      the relationship between trait BDD symptoms and IAcc, and provides preliminary
      evidence that among those with severe BDD symptoms, power may help connect
      individuals with their internal states. Future research testing the mechanisms
      linking BDD symptoms with IAcc, as well as how individuals can better connect
      with their internal experiences is needed..

PMID- 26295933
TI  - Antimicrobial Drug Resistance and Molecular Typing of Salmonella enterica Serovar
      Rissen from Different Sources.
AB  - Salmonella enterica serovar Rissen is one of the most common serovars found in
      pigs and pork products in different countries, including Spain. However,
      information on the molecular bases of antimicrobial drug resistance and the
      population structure of Salmonella Rissen from different sources in Spain is
      limited. The present study focused on 84 isolates collected in Spain from pig and
      beef carcasses, foods and clinical samples associated with sporadic cases of
      gastroenteritis, and one outbreak. The majority of the isolates were resistant to
      tetracycline (73.8%), mainly conferred by tet(A). Resistances to streptomycin
      (aadA1-like, aadA2, and strAB), sulfonamides (sul1, sul2, and sul3), trimethoprim
      (dfrA1-like and dfrA12), ampicillin (blaTEM-1-like), and chloramphenicol (cmlA1
      like) were also detected, with frequencies ranging from 12% to 20.2%. Most of the
      identified genes were carried by integrons, including three class 1 integrons of
      the sul1 type, a class 1 integron of the sul3 type, and the class 2 integron of
      Tn7. Two sul1 integrons, the sul3 integron, and the class 2 integron are first
      reported in Salmonella Rissen. Typing of the isolates with XbaI pulsed-field gel
      electrophoresis detected a major clone, which was circulating in humans and
      animals during the past decade, and was responsible for the outbreak. The
      obtained results are relevant for food safety and public health. 

PMID- 26295934
TI  - Genetic analysis of 17 Y-STR loci in Han, Dong, Miao and Tujia populations from
      Hunan province, central-southern China.

PMID- 26295935
TI  - A Nurse Leadership Project to Improve Health Literacy on a Maternal-Infant Unit.
AB  - OBJECTIVE: To describe how participation in the Sigma Theta Tau International
      Maternal-Child Health Nurse Leadership Academy positioned the authors to lead an
      interdisciplinary team through implementation and evaluation of a change project
      related to patient education based upon national health literacy standards. The
      project goal was to improve patient satisfaction with nurse communication and
      preparation for hospital discharge. DESIGN: Quality improvement.
      SETTING/PARTICIPANTS: Mother/-baby unit of an academic medical center serving a
      high percentage of patients of a minority population and underserved clients.
      INTERVENTION: The five- step intervention included (a) review of current health
      literacy standards, (b) formation of an infrastructure for development and
      evaluation of existing patient education materials, (c) assessment of patient
      education materials currently in use, (d) assessment of literacy level and
      learning styles of new mothers, and (e) provision of continuing education to
      increase knowledge of nurses as patient teachers and of health literacy.
      MEASUREMENT: Mean scores of Hospital Consumer Assessment of Healthcare Providers
      and Systems (HCAHPS) in the domains of patient satisfaction with nurse
      communication and discharge information were used to measure patient satisfaction
      with health communication. RESULTS: Patient satisfaction with nurse communication
      increased from 75.9% to 84.6%. Satisfaction with discharge information increased
      from 84.6% to 98.6%. CONCLUSION: The leadership academy successfully positioned
      the authors to guide an interdisciplinary team through development of a process
      to meet the education and communication needs of patients and improve their
      health literacy. As a result, a positive effect was noted on patient satisfaction
      with health communication.

PMID- 26295936
TI  - How to manage future groundwater resource of China under climate change and
      urbanization: An optimal stage investment design from modern portfolio theory.
AB  - Groundwater management in China has been facing challenges from both climate
      change and urbanization and is considered as a national priority nowadays.
      However, unprecedented uncertainty exists in future scenarios making it difficult
      to formulate management planning paradigms. In this paper, we apply modern
      portfolio theory (MPT) to formulate an optimal stage investment of groundwater
      contamination remediation in China. This approach generates optimal weights of
      investment to each stage of the groundwater management and helps maximize
      expected return while minimizing overall risk in the future. We find that the
      efficient frontier of investment displays an upward-sloping shape in risk-return
      space. The expected value of groundwater vulnerability index increases from
      0.6118 to 0.6230 following with the risk of uncertainty increased from 0.0118 to
      0.0297. If management investment is constrained not to exceed certain total cost
      until 2050 year, the efficient frontier could help decision makers make the most
      appropriate choice on the trade-off between risk and return. 

PMID- 26295937
TI  - A review of a recently emerged technology: Constructed wetland--Microbial fuel
      cells.
AB  - Constructed wetlands (CWs) and microbial fuel cells (MFCs) are compatible
      technologies since both are reliant on the actions of bacteria to remove
      contaminants from wastewater. MFCs require the anode to remain anaerobic with the
      cathode exposed to oxygen while these redox conditions can develop naturally in
      CWs. For this reason, research into combining the two technologies (termed as CW
      MFC) has emerged in recent years with the aim of improving the wastewater
      treatment capacity of wetlands while simultaneously producing electrical power.
      Based on the published work (although limited), this review aims to provide a
      timely, current state-of-the-art in CW-MFC while exploring future challenges and
      research directions. 

PMID- 26295938
TI  - The effect of different aeration conditions in activated sludge--Side-stream
      system on sludge production, sludge degradation rates, active biomass and
      extracellular polymeric substances.
AB  - On-site minimization of excess sludge production is a relevant strategy for the
      operation of small-scale and decentralized wastewater treatment plants. In the
      study, we evaluated the potential of activated sludge systems equipped with side
      stream reactors (SSRs). This study especially focused on how the sequential
      exposure of sludge to different aeration conditions in the side-stream reactors
      influences the overall degradation of sludge and of its specific fractions
      (active biomass, extracellular polymeric substances (EPS), EPS proteins, EPS
      carbohydrates). We found that increasing the solid retention time from 25 to 40
      and 80 days enhanced sludge degradation for all aeration conditions tested in the
      side-stream reactor. Also, the highest specific degradation rate and in turn the
      lowest sludge production were achieved when maintaining aerobic conditions in the
      side-stream reactors. The different sludge fractions in terms of active biomass
      (quantified based on adenosine tri-phosphate (ATP) measurements), EPS proteins
      and EPS carbohydrates were quantified before and after passage through the SSR.
      The relative amounts of active biomass and EPS to volatile suspended solids (VSS)
      did not changed when exposed to different aeration conditions in the SSRs, which
      indicates that long SRT and starvation in the SSRs did not promote the
      degradation of a specific sludge fraction. Overall, our study helps to better
      understand mechanisms of enhanced sludge degradation in systems operated at long
      SRTs. 

PMID- 26295939
TI  - Use of Telemedicine to Improve Adherence to American Diabetes Association
      Standards in Pediatric Type 1 Diabetes.
AB  - BACKGROUND: The American Diabetes Association (ADA) recommends that children with
      type 1 diabetes (T1D) see a multidisciplinary team and have hemoglobin A1c (A1C)
      levels measured every 3 months. Patients in rural areas may not follow guidelines
      because of limited specialty care access. We hypothesized that videoconferencing
      would result in equivalent A1C compared with in-person visits and increased
      compliance with ADA recommendations. MATERIALS AND METHODS: The Barbara Davis
      Center (BDC) (Aurora, CO) telemedicine program provides diabetes care to
      pediatric patients in Casper and Cheyenne, WY, via remote consultation with
      annual in-person visits. Over 27 months, 70 patients were consented, and 54
      patients completed 1 year in the study. RESULTS: Patients were 70% male, with a
      mean age of 12.1 +/- 4.1 years and T1D duration of 5.4 +/- 4.1 years. There was
      no significant change between baseline and 1-year A1C levels for patients with
      data at both time points. Patients saw diabetes specialists an average of 2.0 +/-
      1.3 times per year in the year prior to starting telemedicine and 2.9 +/- 1.3
      times (P < 0.0001) in the year after starting telemedicine. Patients and families
      missed significantly less school and work time to attend appointments.
      CONCLUSIONS: Our study suggests telemedicine is equivalent to in-person visits to
      maintain A1C, whereas families increase the number of visits in line with ADA
      recommendations. Patients and families miss less school and work. Decreased
      financial burden and increased access may improve overall diabetes care and
      compliance for rural patients. Further study is needed to detect long-term
      differences in complications screenings and the financial impact of telemedicine
      on pediatric diabetes care.

PMID- 26295940
TI  - A Complex Network Approach to Distributional Semantic Models.
AB  - A number of studies on network analysis have focused on language networks based
      on free word association, which reflects human lexical knowledge, and have
      demonstrated the small-world and scale-free properties in the word association
      network. Nevertheless, there have been very few attempts at applying network
      analysis to distributional semantic models, despite the fact that these models
      have been studied extensively as computational or cognitive models of human
      lexical knowledge. In this paper, we analyze three network properties, namely,
      small-world, scale-free, and hierarchical properties, of semantic networks
      created by distributional semantic models. We demonstrate that the created
      networks generally exhibit the same properties as word association networks. In
      particular, we show that the distribution of the number of connections in these
      networks follows the truncated power law, which is also observed in an
      association network. This indicates that distributional semantic models can
      provide a plausible model of lexical knowledge. Additionally, the observed
      differences in the network properties of various implementations of
      distributional semantic models are consistently explained or predicted by
      considering the intrinsic semantic features of a word-context matrix and the
      functions of matrix weighting and smoothing. Furthermore, to simulate a semantic
      network with the observed network properties, we propose a new growing network
      model based on the model of Steyvers and Tenenbaum. The idea underlying the
      proposed model is that both preferential and random attachments are required to
      reflect different types of semantic relations in network growth process. We
      demonstrate that this model provides a better explanation of network behaviors
      generated by distributional semantic models. 

PMID- 26295941
TI  - Effects of Microstimulation in the Anterior Intraparietal Area during Three
      Dimensional Shape Categorization.
AB  - The anterior intraparietal area (AIP) of rhesus monkeys is part of the dorsal
      visual stream and contains neurons whose visual response properties are
      commensurate with a role in three-dimensional (3D) shape perception. Neuronal
      responses in AIP signal the depth structure of disparity-defined 3D shapes,
      reflect the choices of monkeys while they categorize 3D shapes, and mirror the
      behavioral variability across different stimulus conditions during 3D-shape
      categorization. However, direct evidence for a role of AIP in 3D-shape perception
      has been lacking. We trained rhesus monkeys to categorize disparity-defined 3D
      shapes and examined AIP's contribution to 3D-shape categorization by
      microstimulating in clusters of 3D-shape selective AIP neurons during task
      performance. We find that microstimulation effects on choices (monkey M1) and
      reaction times (monkey M1 and M2) depend on the 3D-shape preference of the
      stimulated site. Moreover, electrical stimulation of the same cells, during
      either the 3D-shape-categorization task or a saccade task, could affect behavior
      differently. Interestingly, in one monkey we observed a strong correlation
      between the strength of choice-related AIP activity (choice probabilities) and
      the influence of microstimulation on 3D-shape-categorization behavior (choices
      and reaction time). These findings propose AIP as part of the network responsible
      for 3D-shape perception. The results also show that the anterior intraparietal
      cortex contains cells with different tuning properties, i.e. 3D-shape- or saccade
      related, that can be dynamically read out depending on the requirements of the
      task at hand. 

PMID- 26295942
TI  - Confinement-Induced Drug-Tolerance in Mycobacteria Mediated by an Efflux
      Mechanism.
AB  - Tuberculosis (TB) is the world's deadliest curable disease, responsible for an
      estimated 1.5 million deaths annually. A considerable challenge in controlling
      this disease is the prolonged multidrug chemotherapy (6 to 9 months) required to
      overcome drug-tolerant mycobacteria that persist in human tissues, although the
      same drugs can sterilize genetically identical mycobacteria growing in axenic
      culture within days. An essential component of TB infection involves
      intracellular Mycobacterium tuberculosis bacteria that multiply within
      macrophages and are significantly more tolerant to antibiotics compared to
      extracellular mycobacteria. To investigate this aspect of human TB, we created a
      physical cell culture system that mimics confinement of replicating mycobacteria,
      such as in a macrophage during infection. Using this system, we uncovered an
      epigenetic drug-tolerance phenotype that appears when mycobacteria are cultured
      in space-confined bioreactors and disappears in larger volume growth contexts.
      Efflux mechanisms that are induced in space-confined growth environments
      contribute to this drug-tolerance phenotype. Therefore, macrophage-induced drug
      tolerance by mycobacteria may be an effect of confined growth among other
      macrophage-specific mechanisms. 

PMID- 26295943
TI  - SMRT Sequencing of Long Tandem Nucleotide Repeats in SCA10 Reveals Unique Insight
      of Repeat Expansion Structure.
AB  - A large, non-coding ATTCT repeat expansion causes the neurodegenerative disorder,
      spinocerebellar ataxia type 10 (SCA10). In a subset of SCA10 patients,
      interruption motifs are present at the 5' end of the expansion and strongly
      correlate with epileptic seizures. Thus, interruption motifs are a predictor of
      the epileptic phenotype and are hypothesized to act as a phenotypic modifier in
      SCA10. Yet, the exact internal sequence structure of SCA10 expansions remains
      unknown due to limitations in current technologies for sequencing across long
      extended tracts of tandem nucleotide repeats. We used the third generation
      sequencing technology, Single Molecule Real Time (SMRT) sequencing, to obtain
      full-length contiguous expansion sequences, ranging from 2.5 to 4.4 kb in length,
      from three SCA10 patients with different clinical presentations. We obtained
      sequence spanning the entire length of the expansion and identified the structure
      of known and novel interruption motifs within the SCA10 expansion. The exact
      interruption patterns in expanded SCA10 alleles will allow us to further
      investigate the potential contributions of these interrupting sequences to the
      pathogenic modification leading to the epilepsy phenotype in SCA10. Our results
      also demonstrate that SMRT sequencing is useful for deciphering long tandem
      repeats that pose as "gaps" in the human genome sequence. 

PMID- 26295944
TI  - Continuous Ethanol Fermentation of Pretreated Lignocellulosic Biomasses, Waste
      Biomasses, Molasses and Syrup Using the Anaerobic, Thermophilic Bacterium
      Thermoanaerobacter italicus Pentocrobe 411.
AB  - Lignocellosic ethanol production is now at a stage where commercial or semi
      commercial plants are coming online and, provided cost effective production can
      be achieved, lignocellulosic ethanol will become an important part of the world
      bio economy. However, challenges are still to be overcome throughout the process
      and particularly for the fermentation of the complex sugar mixtures resulting
      from the hydrolysis of hemicellulose. Here we describe the continuous
      fermentation of glucose, xylose and arabinose from non-detoxified pretreated
      wheat straw, birch, corn cob, sugar cane bagasse, cardboard, mixed bio waste, oil
      palm empty fruit bunch and frond, sugar cane syrup and sugar cane molasses using
      the anaerobic, thermophilic bacterium Thermoanaerobacter Pentocrobe 411. All
      fermentations resulted in close to maximum theoretical ethanol yields of 0.47
      0.49 g/g (based on glucose, xylose, and arabinose), volumetric ethanol
      productivities of 1.2-2.7 g/L/h and a total sugar conversion of 90-99% including
      glucose, xylose and arabinose. The results solidify the potential of
      Thermoanaerobacter strains as candidates for lignocellulose bioconversion. 

PMID- 26295945
TI  - Adhesion Potential of Intestinal Microbes Predicted by Physico-Chemical
      Characterization Methods.
AB  - Bacterial adhesion to epithelial surfaces affects retention time in the human
      gastro-intestinal tract and therefore significantly contributes to interactions
      between bacteria and their hosts. Bacterial adhesion among other factors is
      strongly influenced by physico-chemical factors. The accurate quantification of
      these physico-chemical factors in adhesion is however limited by the available
      measuring techniques. We evaluated surface charge, interfacial rheology and
      tensiometry (interfacial tension) as novel approaches to quantify these
      interactions and evaluated their biological significance via an adhesion assay
      using intestinal epithelial surface molecules (IESM) for a set of model organisms
      present in the human gastrointestinal tract. Strain pairs of Lactobacillus
      plantarum WCFS1 with its sortase knockout mutant Lb. plantarum NZ7114 and Lb.
      rhamnosus GG with Lb. rhamnosus DSM 20021T were used with Enterococcus faecalis
      JH2-2 as control organism. Intra-species comparison revealed significantly higher
      abilities for Lb. plantarum WCSF1 and Lb. rhamnosus GG vs. Lb. plantarum NZ7114
      and Lb. rhamnosus DSM 20021T to dynamically increase interfacial elasticity (10-2
      vs. 10-3 Pa*m) and reduce interfacial tension (32 vs. 38 mN/m). This further
      correlated for Lb. plantarum WCSF1 and Lb. rhamnosus GG vs. Lb. plantarum NZ7114
      and Lb. rhamnosus DSM 20021T with the decrease of relative hydrophobicity (80-85%
      vs. 57-63%), Zeta potential (-2.9 to -4.5 mV vs. -8.0 to -13.8 mV) and higher
      relative adhesion capacity to IESM (3.0-5.0 vs 1.5-2.2). Highest adhesion to the
      IESM collagen I and fibronectin was found for Lb. plantarum WCFS1 (5.0) and E.
      faecalis JH2-2 (4.2) whereas Lb. rhamnosus GG showed highest adhesion to type II
      mucus (3.8). Significantly reduced adhesion (2 fold) to the tested IESM was
      observed for Lb. plantarum NZ7114 and Lb. rhamnosus DSM 20021T corresponding with
      lower relative hydrophobicity, Zeta potential and abilities to modify interfacial
      elasticity and tension. Conclusively, the use of Zeta potential, interfacial
      elasticity and interfacial tension are proposed as suitable novel descriptive and
      predictive parameters to study the interactions of intestinal microbes with their
      hosts. 

PMID- 26295946
TI  - Acute Myocardial Infarction Is a Risk Factor for New Onset Diabetes in Patients
      with Coronary Artery Disease.
AB  - OBJECTIVE: To test the hypothesis that acute myocardial infarction (AMI) might
      accelerate development of new onset diabetes in patients with coronary artery
      disease independent of known risk factors. METHODS: We conducted a retrospective
      cohort study within COACT (CathOlic medical center percutAneous Coronary
      inTervention) registry. From a total of 9,127 subjects, 2,036 subjects were
      diabetes naive and followed up for at least one year with both index and follow
      up laboratory data about diabetes. Cox proportional hazard model was used to
      derive hazard ratios (HRs) and 95% confidence interval (CI) for new onset
      diabetes associated with AMI in univariate and multivariate analysis after
      adjusting several covariates. RESULTS: The overall hazard for diabetes was higher
      in AMI compared to non-AMI patients (p by log rank <0.01) with HR of 1.78 and 95%
      CI of 1.37-2.32 in univariate analysis. This association remained significant
      after adjusting covariates (HR, 1.54; 95% CI, 1.14-2.07; p<0.01). AMI was an
      independent predictor for higher quartile of WBC count in multivariate ordinal
      logistic regression analysis (OR, 6.75; 95% CI, 5.53-8.22, p<0.01). In subgroup
      analysis, the diabetogenic effect of AMI was more prominent in the subgroup
      without MetS compared to MetS patients (p for interaction<0.05). Compared to the
      reference group of non-AMI+nonMetS, the group of AMI+non-MetS (HR, 2.44; 95% CI,
      1.58-3.76), non-AMI+MetS (HR, 3.42; 95% CI, 2.34-4.98) and AMI+MetS (HR, 4.12;
      95% CI, 2.67-6.36) showed higher HR after adjusting covariates. However, the
      hazard was not different between the non-AMI+MetS and AMI+non-MetS groups.
      CONCLUSIONS: AMI patients have a greater risk of new-onset diabetes when compared
      to non AMI patients, especially those with mild metabolic abnormalities.

PMID- 26295947
TI  - Validation of High Resolution Melting Analysis (HRM) of the Amplified ITS2 Region
      for the Detection and Identification of Yeasts from Clinical Samples: Comparison
      with Culture and MALDI-TOF Based Identification.
AB  - AIM: Candida species are known as opportunistic pathogens, and a possible cause
      of invasive infections. Because of their species-specific antimycotic resistance
      patterns, reliable techniques for their detection, quantification and
      identification are needed. We validated a DNA amplification method for direct
      detection of Candida spp. from clinical samples, namely the ITS2-High Resolution
      Melting Analysis (direct method), by comparing it with a culture and MALDI-TOF
      Mass Spectrometry based method (indirect method) to establish the presence of
      Candida species in three different types of clinical samples. MATERIALS AND
      METHODS: A total of 347 clinical samples, i.e. throat swabs, rectal swabs and
      vaginal swabs, were collected from the gynaecology/obstetrics, intensive care and
      haematology wards at the Ghent University Hospital, Belgium. For the direct
      method, ITS2-HRM was preceded by NucliSENS easyMAG DNA extraction, directly on
      the clinical samples. For the indirect method, clinical samples were cultured on
      Candida ID and individual colonies were identified by MALDI-TOF. RESULTS: For
      83.9% of the samples there was complete concordance between both techniques, i.e.
      the same Candida species were detected in 31.1% of the samples or no Candida
      species were detected in 52.8% of the samples. In 16.1% of the clinical samples,
      discrepant results were obtained, of which only 6.01% were considered as major
      discrepancies. Discrepancies occurred mostly when overall numbers of Candida
      cells in the samples were low and/or when multiple species were present in the
      sample. DISCUSSION: Most of the discrepancies could be decided in the advantage
      of the direct method. This is due to samples in which no yeast could be cultured
      whereas low amounts could be detected by the direct method and to samples in
      which high quantities of Candida robusta according to ITS2-HRM were missed by
      culture on Candida ID agar. It remains to be decided whether the diagnostic
      advantages of the direct method compensate for its disadvantages.

PMID- 26295948
TI  - An Entangled Model for Sustainability Indicators.
AB  - Nowadays the challenge for humanity is to find pathways towards sustainable
      development. Decision makers require a set of sustainability indicators to know
      if the sustainability strategies are following those pathways. There are more
      than one hundred sustainability indicators but they differ on their relative
      importance according to the size of the locality and change on time. The
      resources needed to follow these sustainability indicators are scarce and in some
      instances finite, especially in smaller regions. Therefore strategies to select
      set of these indicators are useful for decision makers responsible for monitoring
      sustainability. In this paper we propose a model for the identification and
      selection of a set of sustainability indicators that adequately represents human
      systems. In developing this model, we applied evolutionary dynamics in a space
      where sustainability indicators are fundamental entities interconnected by an
      interaction matrix. we used a fixed interaction that simulates the current
      context for the city of Cuernavaca, Mexico as an example. We were able to
      identify and define relevant sets indicators for the system by using the Pareto
      principle. In this case we identified a set of sixteen sustainability indicators
      with more than 80% of the total strength. This set presents resilience to
      perturbations. For the Tangled Nature framework we provided a manner of treating
      different contexts (i.e., cities, counties, states, regions, countries,
      continents or the whole planet), dealing with small dimensions. This model
      provides decision makers with a valuable tool to select sustainability indicators
      set for towns, cities, regions, countries, continents or the entire planet
      according to a coevolutionary framework. The social legitimacy can arise from the
      fact that each individual indicator must be selected from those that are most
      important for the subject community. 

PMID- 26295951
TI  - Editorial: Emerging Formulation Design and Drug Delivery Systems for Inhaled
      Therapy.

PMID- 26295950
TI  - Enhancing the performance of LC-MS for intact protein analysis by counteracting
      the signal suppression effects of trifluoroacetic acid during electrospray.
AB  - We develop an acidic vapor assisted electrospray ionization strategy within an
      enclosed electrospray ionization source to counteract the ion suppression effects
      caused by trifluoroacetic acid. The mass spectrometry signal intensity of intact
      proteins was improved 10 times and the number of valid signals for E. coli intact
      protein samples was improved 96% by using this strategy. 

PMID- 26295949
TI  - Active Transport of Phosphorylated Carbohydrates Promotes Intestinal Colonization
      and Transmission of a Bacterial Pathogen.
AB  - Efficient acquisition of extracellular nutrients is essential for bacterial
      pathogenesis, however the identities and mechanisms for transport of many of
      these substrates remain unclear. Here, we investigate the predicted iron-binding
      transporter AfuABC and its role in bacterial pathogenesis in vivo. By
      crystallographic, biophysical and in vivo approaches, we show that AfuABC is in
      fact a cyclic hexose/heptose-phosphate transporter with high selectivity and
      specificity for a set of ubiquitous metabolites (glucose-6-phosphate, fructose-6
      phosphate and sedoheptulose-7-phosphate). AfuABC is conserved across a wide range
      of bacterial genera, including the enteric pathogens EHEC O157:H7 and its murine
      specific relative Citrobacter rodentium, where it lies adjacent to genes
      implicated in sugar sensing and acquisition. C. rodentium DeltaafuA was
      significantly impaired in an in vivo murine competitive assay as well as its
      ability to transmit infection from an afflicted to a naive murine host. Sugar
      phosphates were present in normal and infected intestinal mucus and stool
      samples, indicating that these metabolites are available within the intestinal
      lumen for enteric bacteria to import during infection. Our study shows that
      AfuABC-dependent uptake of sugar-phosphates plays a critical role during enteric
      bacterial infection and uncovers previously unrecognized roles for these
      metabolites as important contributors to successful pathogenesis. 

PMID- 26295952
TI  - Nanocarriers in Improved Heparin Delivery: Recent Updates.
AB  - Heparin, a well known drug for anticoagulant therapy and prophylaxis of deep vein
      thrombosis and coronary syndromes, is also involved in numerous pathological
      processes such as inflammation, immune cell migration, tumor cell metastasis,
      smooth muscle cell proliferation etc. Though heparin is a clinically used
      anticoagulant with minimal side effects and drug interactions, its clinical use
      is limited due to parenteral administration. Alternatively, noninvasive delivery
      approaches such as oral, nasal, pulmonary or transdermal route are being explored
      that may deal with problems associated with parenteral heparin without
      compromising therapeutic benefits. For the successful noninvasive delivery of
      such a large drug candidate, the biological and biochemical barriers must be
      overcome to achieve a clinically acceptable therapeutic advantage. Nanocarriers
      significantly improve the pharmacokinetics and clinical effectiveness of the
      loaded therapeutics by either protecting them from unfavorable bioenvironment or
      modifying their release at the target site. Novel carriers such as liposomes,
      nanoparticles, dendrimers etc. have been developed to improve the bioavailability
      of heparin through various routes of delivery. Overall, the present review
      provides complete insight to the research that has been carried out for heparin
      delivery through various routes. 

PMID- 26295953
TI  - In Situ Generation of Cellulose Nanocrystals in Polycaprolactone Nanofibers:
      Effects on Crystallinity, Mechanical Strength, Biocompatibility, and Biomimetic
      Mineralization.
AB  - Post-electrospinning treatment is a facile process to improve the properties of
      electrospun nanofibers for various applications. This technique is commonly used
      when direct electrospinning is not a suitable option to fabricate a nonwoven
      membrane of the desired polymer in a preferred morphology. In this study, a
      representative natural-synthetic hybrid of cellulose acetate (CA) and
      polycaprolactone (PCL) in different ratios was fabricated using an
      electrospinning process, and CA in the hybrid fiber was transformed into
      cellulose (CL) by post-electrospinning treatment via alkaline saponification.
      Scanning electron microscopy was employed to study the effects of polymer
      composition and subsequent saponification on the morphology of the nanofibers.
      Increasing the PCL content in the PCL/CA blend solution caused a gradual decrease
      in viscosity, resulting in smoother and more uniform fibers. The saponification
      of fibers lead to pronounced changes in the physicochemical properties. The
      crystallinity of the PCL in the composite fiber was varied according to the
      composition of the component polymers. The water contact angle was considerably
      decreased (from 124 degrees  to less than 20 degrees ), and the mechanical
      properties were greatly enhanced (Young's Modulus was improved by ~20-30 fold,
      tensile strength by 3-4 fold, and tensile stress by ~2-4 fold) compared to those
      of PCL and PCL/CA membranes. Regeneration of cellulose chains in the nanofibers
      increased the number of hydroxyl groups, which increased the hydrogen bonding,
      thereby improving the mechanical properties and wettability of the composite
      nanofibers. The improved wettability and presence of surface functional groups
      enhanced the ability to nucleate bioactive calcium phosphate crystals throughout
      the matrix when exposed to a simulated body fluid solution. Experimental results
      of cell viability assay, confocal microscopy, and scanning electron microscopy
      imaging showed that the fabricated nanofibrous membranes have excellent ability
      for MC3T3-E1 cell proliferation and growth. Given the versatility and widespread
      use of cellulose-synthetic hybrid systems in the construction of tissue
      engineered scaffolds, this work provides a novel strategy to fabricate the
      biopolymer-based materials for applications in tissue engineering and
      regenerative medicine. 

PMID- 26295954
TI  - Primary Productivity and Precipitation-Use Efficiency in Temperate Grassland in
      the Loess Plateau of China.
AB  - Clarifying spatial variations in aboveground net primary productivity (ANPP) and
      precipitation-use efficiency (PUE) of grasslands is critical for effective
      prediction of the response of terrestrial ecosystem carbon and water cycle to
      future climate change. Though the combination use of remote sensing products and
      in situ ANPP measurements, we quantified the effects of climatic [mean annual
      precipitation (MAP) and precipitation seasonal distribution (PSD)], biotic [leaf
      area index (LAI)] and abiotic [slope gradient, aspect, soil water storage (SWS)
      and other soil physical properties] factors on the spatial variations in ANPP and
      PUE across different grassland types (i.e., meadow steppe, typical steppe and
      desert steppe) in the Loess Plateau. Based on the study, ANPP increased
      exponentially with MAP for the entire temperate grassland; suggesting that PUE
      increased with increasing MAP. Also PSD had a significant effect on ANPP and PUE;
      where more even PSD favored higher ANPP and PUE. Then MAP, more than PSD,
      explained spatial variations in typical steppe and desert steppe. However, PSD
      was the dominant driving factor of spatial variations in ANPP of meadow steppe.
      This suggested that in terms of spatial variations in ANPP of meadow steppe,
      change in PSD due to climate change was more important than that in total annual
      precipitation. LAI explained 78% of spatial PUE in the entire Loess Plateau
      temperate grassland. As such, LAI was the primary driving factor of spatial
      variations in PUE. Although the effect of SWS on ANPP and PUE was significant, it
      was nonetheless less than that of precipitation and vegetation. We therefore
      concluded that changes in vegetation structure and consequently in LAI and/or
      altered pattern of seasonal distribution of rainfall due to global climate change
      could significantly influence ecosystem carbon and water cycle in temperate
      grasslands. 

PMID- 26295955
TI  - Cost-Effectiveness of Introducing the SILCS Diaphragm in South Africa.
AB  - BACKGROUND: Though South Africa has high contraceptive use, unintended
      pregnancies are still widespread. The SILCS diaphragm could reduce the number of
      women with unmet need by introducing a discreet, woman-initiated, non-hormonal
      barrier method to the contraceptive method mix. METHODS: A decision model was
      built to estimate the impact and cost-effectiveness of the introduction of the
      SILCS diaphragm in Gauteng among women with unmet need for contraception in terms
      of unintended and mistimed pregnancies averted, assuming that the available
      contraceptives on the market were not a satisfying option for those women. Full
      costs were estimated both from a provider's and user's perspective, which also
      accounts for women's travel and opportunity cost of time, assuming a 5% uptake
      among women with unmet contraceptive need. The incremental cost-effectiveness
      ratio is computed at five and 10 years after introduction to allow for a
      distribution of fixed costs over time. A probabilistic sensitivity analysis was
      conducted to incorporate decision uncertainty. RESULTS: The introduction of the
      SILCS diaphragm in Gauteng could prevent an estimated 8,365 unintended
      pregnancies and 2,117 abortions over five years, at an annual estimated cost of
      US$55 per woman. This comes to a cost per pregnancy averted of US$153 and US$171
      from a user's and provider's perspectives, respectively, with slightly lower unit
      costs at 10 years. Major cost drivers will be the price of the SILCS diaphragm
      and the contraceptive gel, given their large contribution to total costs (around
      60%). CONCLUSIONS: The introduction of the SILCS diaphragm in the public sector
      is likely to provide protection for some women for whom current contraceptive
      technologies are not an option. However to realize its potential, targeting will
      be needed to reach women with unmet need and those with likely high adherence.
      Further analyses are needed among potential users to optimize the introduction
      strategy.

PMID- 26295956
TI  - Revisiting the Function of CDK7 in Transcription by Virtue of a Recently
      Described TFIIH Kinase Inhibitor.
AB  - In this issue of Molecular Cell, Nilson et al. (2015) took advantage of THZ1, a
      recently described covalent inhibitor of the TFIIH kinase CDK7, to further
      characterize the role of this enzyme in the early stages of transcription and
      postprocessing events. They unveiled an unexpected function of CDK7 in RNA
      polymerase II pausing and mRNA capping. 

PMID- 26295957
TI  - Shockingly Early: Chromatin-Mediated Loss of the Heat Shock Response.
AB  - In this issue of Molecular Cell, Labbadia and Morimoto (2015) show that there is
      a precipitous decline in stress resistance at the onset of reproduction in C.
      elegans and that this transition is regulated by changes in repressive chromatin
      marks. 

PMID- 26295958
TI  - Keeping Oxidative Metabolism on Time: Mitochondria as an Autonomous Redox
      Pacemaker Animated by H2O2 and Peroxiredoxin.
AB  - In this issue of Molecular Cell, Kil et al. (2015) provide evidence for self
      sustained circadian oscillations of the hyperoxidation of the mitochondrial
      Peroxiredoxin, PrxIII, and cytosolic release of mitochondrial H2O2, which might
      constitute one biochemical output coupling metabolic changes and transcriptional
      based core clocks. 

PMID- 26295959
TI  - Metabolic Remodeling in Times of Stress: Who Shoots Faster than His Shadow?
AB  - A sudden increase in pentose phosphate pathway (PPP) activity, the fastest known
      cellular response to oxidative stress, protects cells through timely generation
      of NADPH. Originally discovered in budding yeast, Kuehne and colleagues
      demonstrate the conservation of this mechanism in human cells and reveal its
      importance for skin cells exposed to UV light. 

PMID- 26295960
TI  - Organelle-Specific Initiation of Autophagy.
AB  - Autophagy constitutes a prominent mechanism through which eukaryotic cells
      preserve homeostasis in baseline conditions and in response to perturbations of
      the intracellular or extracellular microenvironment. Autophagic responses can be
      relatively non-selective or target a specific subcellular compartment. At least
      in part, this depends on the balance between the availability of autophagic
      substrates ("offer") and the cellular need of autophagic products or functions
      for adaptation ("demand"). Irrespective of cargo specificity, adaptive autophagy
      relies on a panel of sensors that detect potentially dangerous cues and convert
      them into signals that are ultimately relayed to the autophagic machinery. Here,
      we summarize the molecular systems through which specific subcellular
      compartments-including the nucleus, mitochondria, plasma membrane, reticular
      apparatus, and cytosol-convert homeostatic perturbations into an increased offer
      of autophagic substrates or an accrued cellular demand for autophagic products or
      functions. 

PMID- 26295961
TI  - Aub and Ago3 Are Recruited to Nuage through Two Mechanisms to Form a Ping-Pong
      Complex Assembled by Krimper.
AB  - In Drosophila, two Piwi proteins, Aubergine (Aub) and Argonaute-3 (Ago3),
      localize to perinuclear "nuage" granules and use guide piRNAs to target and
      destroy transposable element transcripts. We find that Aub and Ago3 are recruited
      to nuage by two different mechanisms. Aub requires a piRNA guide for nuage
      recruitment, indicating that its localization depends on recognition of RNA
      targets. Ago3 is recruited to nuage independently of a piRNA cargo and relies on
      interaction with Krimper, a stable component of nuage that is able to aggregate
      in the absence of other nuage proteins. We show that Krimper interacts directly
      with Aub and Ago3 to coordinate the assembly of the ping-pong piRNA processing
      (4P) complex. Symmetrical dimethylated arginines are required for Aub to interact
      with Krimper, but they are dispensable for Ago3 to bind Krimper. Our study
      reveals a multi-step process responsible for the assembly and function of nuage
      complexes in piRNA-guided transposon repression. 

PMID- 26295962
TI  - Condensin- and Replication-Mediated Bacterial Chromosome Folding and Origin
      Condensation Revealed by Hi-C and Super-resolution Imaging.
AB  - Chromosomes of a broad range of species, from bacteria to mammals, are structured
      by large topological domains whose precise functional roles and regulatory
      mechanisms remain elusive. Here, we combine super-resolution microscopies and
      chromosome-capture technologies to unravel the higher-order organization of the
      Bacillus subtilis chromosome and its dynamic rearrangements during the cell
      cycle. We decipher the fine 3D architecture of the origin domain, revealing
      folding motifs regulated by condensin-like complexes. This organization, along
      with global folding throughout the genome, is present before replication,
      disrupted by active DNA replication, and re-established thereafter. Single-cell
      analysis revealed a strict correspondence between sub-cellular localization of
      origin domains and their condensation state. Our results suggest that the precise
      3D folding pattern of the origin domain plays a role in the regulation of
      replication initiation, chromosome organization, and DNA segregation. 

PMID- 26295963
TI  - CIMAvax EGF (EGF-P64K) vaccine for the treatment of non-small-cell lung cancer.
AB  - Epidermal growth factor receptor (EGFR) is overexpressed in many epithelial
      tumors and its role in the development of non-small-cell lung cancer (NSCLC) is
      widely documented. CIMAvax-EGF is a therapeutic cancer vaccine composed by
      recombinant EGF conjugated to a carrier protein and emulsified in Montanide
      ISA51. Vaccination induces antibodies against self-EGF that block EGF-EGFR
      interaction and inhibit EGFR phosphorylation. Five clinical trials were conducted
      to optimize vaccine formulation and schedule. Then, two randomized studies were
      completed in advanced NSCLC, where CIMAvax-EGF was administered after
      chemotherapy, as 'switch maintenance'. The vaccine was very well tolerated and
      the most frequent adverse events consisted of grade 1/2 injection site reactions,
      fever, headache, vomiting and chills. CIMAvax was immunogenic and EGF
      concentration was reduced after vaccination. Subjects receiving a minimum of 4
      vaccine doses had a significant survival advantage. NSCLC patients with high EGF
      concentration at baseline had the largest benefit, comparable with best
      maintenance therapies. 

PMID- 26295964
TI  - A Pilot Study on Integrating Videography and Environmental Microbial Sampling to
      Model Fecal Bacterial Exposures in Peri-Urban Tanzania.
AB  - Diarrheal diseases are a leading cause of under-five mortality and morbidity in
      sub-Saharan Africa. Quantitative exposure modeling provides opportunities to
      investigate the relative importance of fecal-oral transmission routes (e.g.
      hands, water, food) responsible for diarrheal disease. Modeling, however,
      requires accurate descriptions of individuals' interactions with the environment
      (i.e., activity data). Such activity data are largely lacking for people in low
      income settings. In the present study, we collected activity data and
      microbiological sampling data to develop a quantitative microbial exposure model
      for two female caretakers in peri-urban Tanzania. Activity data were combined
      with microbiological data of contacted surfaces and fomites (e.g. broom handle,
      soil, clothing) to develop example exposure profiles describing second-by-second
      estimates of fecal indicator bacteria (E. coli and enterococci) concentrations on
      the caretaker's hands. The study demonstrates the application and utility of
      video activity data to quantify exposure factors for people in low-income
      countries and apply these factors to understand fecal contamination exposure
      pathways. This study provides both a methodological approach for the design and
      implementation of larger studies, and preliminary data suggesting contacts with
      dirt and sand may be important mechanisms of hand contamination. Increasing the
      scale of activity data collection and modeling to investigate individual-level
      exposure profiles within target populations for specific exposure scenarios would
      provide opportunities to identify the relative importance of fecal-oral disease
      transmission routes. 

PMID- 26295965
TI  - Electrical nanowell diagnostics sensors for rapid and ultrasensitive detection of
      prostate-specific antigen.
AB  - AIM: Alumina nanowell based disposable diagnostic biosensor for detecting and
      quantifying levels of prostate-specific antigen (PSA) from human serum has been
      designed, fabricated and tested. MATERIALS & METHODS: The biosensors were
      designed by integrating nanoporous alumina membranes onto printed circuit board
      platforms, resulting in the generation of high-density nanowell arrays with gold
      base electrodes. The size and density of the nanowells were leveraged toward
      achieving sieving action for size-based exclusion of nonspecific molecules and
      size-based confinement of the target PSA molecules. RESULTS & CONCLUSION: We
      demonstrated PSA detection between 0.01 and 1000 ng/ml and detection and
      quantification of PSA from a 17 patient cohort validated using the Beckman Access
      system with >95% correlation.

PMID- 26295966
TI  - Impact of Prophylactic Continuous Positive Airway Pressure on Transient Tachypnea
      of the Newborn and Neonatal Intensive Care Admission in Newborns Delivered by
      Elective Cesarean Section.
AB  - OBJECTIVE: This study aims to evaluate the effect of the prophylactic continuous
      positive airway pressure (CPAP) administration in the delivery room to newborns
      who were delivered by elective cesarean section (CS). STUDY DESIGN: Inborn
      infants with gestational age between 34(0/7) to 38(6/7) and born by elective CS
      were prospectively randomized to receive either prophylactic CPAP for 20 minutes
      via face mask or standardized care without CPAP in the delivery room. Primary
      outcomes were the incidence of transient tachypnea of the newborn (TTN) and
      neonatal intensive care unit (NICU) admission due to respiratory distress.
      RESULTS: A total of 259 infants with a mean gestational age of 37.7 +/- 0.8 weeks
      and birth weight of 3,244 +/- 477 g were included. A total of 134 infants
      received prophylactic CPAP and 125 received control standard care. The rate of
      NICU admission was significantly lower in prophylactic CPAP group (p = 0.045).
      Although the rate of TTN was lower in the prophylactic CPAP group, the difference
      was not statistically significant (p = 0.059). The rate of NICU admission due to
      respiratory distress was significantly higher in late-preterm cohort than early
      term cohort (p < 0.0001). CONCLUSION: Prophylactic CPAP administration decreases
      the rate of NICU admission without any side effect in late-preterm and early-term
      infants delivered by elective CS.

PMID- 26295967
TI  - Improved Perinatal Mortality in Twins--Changing Practice and Technologies.
AB  - OBJECTIVE: We set out to examine rates of perinatal mortality in twin pregnancies
      over a 17-year study period. Changes in mode of delivery were also examined as
      well as causes of death in twin mortalities. STUDY DESIGN: This retrospective
      cohort study was performed at three large tertiary referral centers from 1996 to
      2012. It included all normally formed twin infants with a birth weight more than
      500 g. All cases of perinatal mortality in twin pregnancies (infants more than
      500 g who suffered an intrauterine or early neonatal (<= 7 days of age) death
      were recorded. The changing rate of cesarean delivery as well as varying causes
      of death in twins over the course of the study were also examined. RESULTS:
      During the study period, there were 395,830 pregnancies across the three
      institutions, this included 6,727 twin gestations. The perinatal mortality rate
      was 21.5/1,000 twin infants. The perinatal mortality rate in twins decreased over
      the study period (p = 0.0006; R (2) = 0.55; slope = -1.2). Rates of cesarean
      delivery in twin gestations were found to have increased over the course of the
      study (p < 0.0001; R (2) = 0.84; slope = 1.7). There were 288 intrauterine and
      early neonatal deaths in twin infants, 50% (147/288) occurred in twins born
      extremely premature (< 26 weeks). Prematurity was the leading cause of mortality
      in twins, followed by twin-to-twin transfusion syndrome (TTTS). TTTS was found to
      have a decreasing contribution to perinatal mortality during the study (p =
      0.008; R (2) = 0.38; slope = -1.5). CONCLUSION: The perinatal mortality rate in
      twins improved during the study. The rate of cesarean delivery increased by 1.7%
      for each year of the study, culminating in a cesarean delivery rate of 62% in
      2012. TTTS made a decreasing contribution to the mortality rate in twins during
      the study.

PMID- 26295968
TI  - Determinants of Severe Metabolic Bone Disease in Very Low-Birth-Weight Infants
      with Severe Bronchopulmonary Dysplasia Admitted to a Tertiary Referral Center.
AB  - OBJECTIVE: Nonrespiratory comorbidities are common among preterm infants with
      severe bronchopulmonary dysplasia (BPD) referred to tertiary perinatal centers.
      We evaluated the incidence, severity, and risk factors for metabolic bone disease
      (MBD) in this population. STUDY DESIGN: We conducted a retrospective cohort study
      of all infants born <= 1,500 g who were diagnosed with severe BPD in our single,
      tertiary referral center between September 2010 and October 2012. MBD severity
      was classified by serial radiography. RESULTS: Among the 83 infants diagnosed
      with severe BPD, 26 (31%) developed severe MBD (rickets). Male gender and lower
      gestational age and birth weight were associated with increased odds of severe
      MBD. After adjustment for these potential confounders, cytomegalovirus infection,
      postnatal growth restriction, surgical necrotizing enterocolitis, and blood
      culture confirmed sepsis were associated with increased odds of severe MBD. The
      cumulative duration of therapy with furosemide, hydrocortisone, and prednisolone
      each correlated with significantly greater probability of severe MBD.
      CONCLUSIONS: Severe MBD was common in this referral-based cohort with severe BPD.
      The high incidence in this population is likely explained by the coexistence of
      multiple exposures and comorbidities associated with bone demineralization.

PMID- 26295969
TI  - Pennogenyl Saponins from Paris quadrifolia L. Induce Extrinsic and Intrinsic
      Pathway of Apoptosis in Human Cervical Cancer HeLa Cells.
AB  - Pennogenyl saponins are the active compounds of large number of plant species and
      consequently many polyherbal formulations. Hence, great interest has been shown
      in their characterization and in the investigation of their pharmacological and
      biological properties, especially anticancer. This present study reports on the
      evaluation of cytotoxic effects and explanation of the molecular mechanisms of
      action of the two pennogenyl saponins (PS 1 and PS 2) isolated from Paris
      quadrifolia L. rhizomes on human cervical adenocarcinoma cell line HeLa. To
      determine the viability of the cells treated with the compounds we used real-time
      cell proliferation analysis and found that the pennogenyl saponins PS 1 and PS 2
      strongly inhibited the tumor cells growth with IC50 values of 1.11 +/- 0.04
      MUg/ml and 0.87 +/- 0.05 MUg/ml, respectively. The flow cytometry analysis
      indicated that the two compounds induced apoptosis in a dose-dependent manner and
      decreased mitochondrial membrane potential in HeLa cells in the early stage of
      apoptosis. Quantitative PCR and Western Blot analysis showed that the two
      saponins significantly increased mRNA expression of FADD and BID as well as
      induced caspase-8 via increased of procaspase-8 processing in the treated cells.
      The results of this study suggest that both the extrinsic death receptor and
      intrinsic mitochondrial pathways are involved in the programmed cell death. 

PMID- 26295970
TI  - A Representational Similarity Analysis of the Dynamics of Object Processing Using
      Single-Trial EEG Classification.
AB  - The recognition of object categories is effortlessly accomplished in everyday
      life, yet its neural underpinnings remain not fully understood. In this
      electroencephalography (EEG) study, we used single-trial classification to
      perform a Representational Similarity Analysis (RSA) of categorical
      representation of objects in human visual cortex. Brain responses were recorded
      while participants viewed a set of 72 photographs of objects with a planned
      category structure. The Representational Dissimilarity Matrix (RDM) used for RSA
      was derived from confusions of a linear classifier operating on single EEG
      trials. In contrast to past studies, which used pairwise correlation or
      classification to derive the RDM, we used confusion matrices from multi-class
      classifications, which provided novel self-similarity measures that were used to
      derive the overall size of the representational space. We additionally performed
      classifications on subsets of the brain response in order to identify spatial and
      temporal EEG components that best discriminated object categories and exemplars.
      Results from category-level classifications revealed that brain responses to
      images of human faces formed the most distinct category, while responses to
      images from the two inanimate categories formed a single category cluster.
      Exemplar-level classifications produced a broadly similar category structure, as
      well as sub-clusters corresponding to natural language categories. Spatiotemporal
      components of the brain response that differentiated exemplars within a category
      were found to differ from those implicated in differentiating between categories.
      Our results show that a classification approach can be successfully applied to
      single-trial scalp-recorded EEG to recover fine-grained object category
      structure, as well as to identify interpretable spatiotemporal components
      underlying object processing. Finally, object category can be decoded from purely
      temporal information recorded at single electrodes. 

PMID- 26295971
TI  - To 'enable our legal product to compete effectively with the transit market':
      British American Tobacco's strategies in Thailand following the 1990 GATT
      dispute.
AB  - The opening of the Thai tobacco market, following action brought by the US Trade
      Representative under the General Agreement on Tariffs and Trade, is seen as a key
      case study of the tensions between trade and health policy. Interpretations of
      the dispute cast it, either as an example of how trade agreements undermine
      national policy-making, or how governments can adopt effective public health
      protections compliant with international trade rules. As a UK-based company,
      British American Tobacco has been regarded as peripheral to this dispute. This
      paper argues that its close monitoring of the illegal trade during this period,
      the role of smuggling in the company's global business strategy, and its
      management of the relative supply and pricing of legal and illegal products after
      market opening provide a fuller understanding of the interests and roles of
      transnational tobacco companies and the government in this dispute. The findings
      have important policy implications, notably the role of effective governance in
      countries facing pressure to open their tobacco sectors, need to better
      understand corporate-level activities within an increasingly globalised tobacco
      industry, and need to address the intertwined legal and illegal trade in
      implementing the WHO Framework Convention on Tobacco Control Protocol to
      Eliminate Illicit Trade in Tobacco Products.

PMID- 26295974
TI  - Update: routine screening for antibodies to human immunodeficiency virus,
      civilian applicants for U.S. military service and U.S. Armed Forces, active and
      reserve components, January 2010-June 2015.
AB  - This report contains an update through June 2015 of the results of routine
      screening for antibodies to the human immunodeficiency virus (HIV) among civilian
      applicants for military service and among members of the active and reserve
      components of the U.S. Armed Forces. Seroprevalences among civilian applicants in
      2014 and the first half of 2015 (0.21 and 0.22 per 1,000 tested, respectively)
      were markedly lower than in 2012 (0.28 per 1,000 tested). In nearly every
      component of every military service, seroprevalences in 2014 and 2015 were either
      lower than, or relatively similar to, prevalences in prior years; however, in the
      Army National Guard, seroprevalences increased each year and approximately
      doubled from 2010 (0.18 per 1,000 tested) to 2014-2015 (0.36-0.39 per 1,000
      tested). Among active and reserve component service members, seroprevalences
      continue to be higher among Army and Navy members and males than their respective
      counterparts. 

PMID- 26295973
TI  - Identification of Driving ALK Fusion Genes and Genomic Landscape of Medullary
      Thyroid Cancer.
AB  - The genetic landscape of medullary thyroid cancer (MTC) is not yet fully
      understood, although some oncogenic mutations have been identified. To explore
      genetic profiles of MTCs, formalin-fixed, paraffin-embedded tumor tissues from
      MTC patients were assayed on the Ion AmpliSeq Cancer Panel v2. Eighty-four
      sporadic MTC samples and 36 paired normal thyroid tissues were successfully
      sequenced. We discovered 101 hotspot mutations in 18 genes in the 84 MTC tissue
      samples. The most common mutation was in the ret proto-oncogene, which occurred
      in 47 cases followed by mutations in genes encoding Harvey rat sarcoma viral
      oncogene homolog (N = 14), serine/threonine kinase 11 (N = 11), v-kit Hardy
      Zuckerman 4 feline sarcoma viral oncogene homolog (N = 6), mutL homolog 1 (N =
      4), Kiesten rat sarcoma viral oncogene homolog (N = 3) and MET proto-oncogene (N
      = 3). We also evaluated anaplastic lymphoma kinase (ALK) rearrangement by
      immunohistochemistry and break-apart fluorescence in situ hybridization (FISH).
      Two of 98 screened cases were positive for ALK FISH. To identify the genomic
      breakpoint and 5' fusion partner of ALK, customized targeted cancer panel
      sequencing was performed using DNA from tumor samples of the two patients.
      Glutamine:fructose-6-phosphate transaminase 1 (GFPT1)-ALK and echinoderm
      microtubule-associated protein-like 4 (EML4)-ALK fusions were identified.
      Additional PCR analysis, followed by Sanger sequencing, confirmed the GFPT1-ALK
      fusion, indicating that the fusion is a result of intra-chromosomal translocation
      or deletion. Notably, a metastatic MTC case harboring the EML4-ALK fusion showed
      a dramatic response to an ALK inhibitor, crizotinib. In conclusion, we found
      several genetic mutations in MTC and are the first to identify ALK fusions in
      MTC. Our results suggest that the EML4-ALK fusion in MTC may be a potential
      driver mutation and a valid target of ALK inhibitors. Furthermore, the GFPT1-ALK
      fusion may be a potential candidate for molecular target therapy. 

PMID- 26295972
TI  - Colorectal cancer models for novel drug discovery.
AB  - INTRODUCTION: Despite increased screening rates and advances in targeted therapy,
      colorectal cancer (CRC) remains the third leading cause of cancer-related
      mortality. CRC models that recapitulate key features of human disease are
      essential to the development of novel and effective therapeutics. Classic methods
      of modeling CRC such as human cell lines and xenograft mice, while useful for
      many applications, carry significant limitations. Recently developed in vitro and
      in vivo models overcome some of these deficiencies and thus can be utilized to
      better model CRC for mechanistic and translational research. AREAS COVERED: The
      authors review established models of in vitro cell culture and describe advances
      in organoid culture for studying normal and malignant intestine. They also
      discuss key features of classic xenograft models and describe other approaches
      for in vivo CRC research, including patient-derived xenograft, carcinogen
      induced, orthotopic transplantation and transgenic mouse models. We also describe
      mouse models of metastatic CRC. EXPERT OPINION: No single model is optimal for
      drug discovery in CRC. Genetically engineered models overcome many limitations of
      xenograft models. Three-dimensional organoids can be efficiently derived from
      both normal and malignant tissue for large-scale in vitro and in vivo
      (transplantation) studies and are thus a significant advance in CRC drug
      discovery.

PMID- 26295975
TI  - Durations of military service after diagnoses of HIV-1 infections among active
      component members of the U.S. Armed Forces, 1990-2013.
AB  - This report describes the trends in length of military service for active
      component members of the U.S. Armed Forces who were diagnosed with human
      immunodeficiency virus type 1 (HIV-1) infections during 1990-2013. Durations of
      service after service members' initial diagnoses of HIV-1 infection were compared
      for five different cohorts that corresponded to when diagnoses were made during
      the 5-year intervals beginning in 1990, 1995, 2000, and 2005, and the 4-year
      interval of 2010-2013. By several measures, the durations of service after
      initial diagnoses of HIV-1 infection increased from the earliest to the later
      cohorts. The findings are discussed in the context of changes in several factors
      during the surveillance period: the growing availability and effectiveness of
      treatments for HIV-1 disease; the stigmas associated with the diagnosis of HIV-1
      infection and its link to homosexuality; and the changes in U.S. military policy
      about the inclusion of homosexuals in its ranks. Also discussed are the
      limitations of the estimates for the most recent cohorts and the future prospects
      for continued lengthening of service for those infected with HIV-1. 

PMID- 26295976
TI  - Case report: probable murine typhus at Joint Base San Antonio, TX.

PMID- 26295977
TI  - Morbidity burdens attributable to various illnesses and injuries in deployed (per
      Theater Medical Data Store [TMDS]) active and reserve component service members,
      U.S. Armed Forces, 2008-2014.
AB  - This report estimates illness and injury-related morbidity and the healthcare
      "burden" for service members during deployments to the CENTCOM and AFRICOM
      theaters of operation during 2008-2014. During the 7-year surveillance period, a
      total of 2,863,834 medical encounters occurred among 1,596,935 service members
      who were deployed. Four burden categories comprised 50% or more of the total
      healthcare burden among both male and female deployers: injury and poisoning,
      mental disorders, musculoskeletal diseases, and signs and symptoms. In both
      genders, injuries and poisonings, and signs and symptoms, were the top two
      categories that affected the most individuals. Both genders had the same top four
      hospitalization categories: injuries and poisonings, signs and symptoms,
      genitourinary diseases, and digestive diseases. The limitations of the data used
      in the analysis are discussed. 

PMID- 26295979
TI  - Correction for Yokosawa et al., C-Terminal Region of STAT-1alpha Is Not Necessary
      for Its Ubiquitination and Degradation Caused by Mumps Virus V Protein.

PMID- 26295980
TI  - Effects of Graphene Oxide and Oxidized Carbon Nanotubes on the Cellular Division,
      Microstructure, Uptake, Oxidative Stress, and Metabolic Profiles.
AB  - Nanomaterial oxides are common formations of nanomaterials in the natural
      environment. Herein, the nanotoxicology of typical graphene oxide (GO) and
      carboxyl single-walled carbon nanotubes (C-SWCNT) was compared. The results
      showed that cell division of Chlorella vulgaris was promoted at 24 h and then
      inhibited at 96 h after nanomaterial exposure. At 96 h, GO and C-SWCNT inhibited
      the rates of cell division by 0.08-15% and 0.8-28.3%, respectively. Both GO and C
      SWCNT covered the cell surface, but the uptake percentage of C-SWCNT was 2-fold
      higher than that of GO. C-SWCNT induced stronger plasmolysis and mitochondrial
      membrane potential loss and decreased the cell viability to a greater extent than
      GO. Moreover, C-SWCNT-exposed cells exhibited more starch grains and lysosome
      formation and higher reactive oxygen species (ROS) levels than GO-exposed cells.
      Metabolomics analysis revealed significant differences in the metabolic profiles
      among the control, C-SWCNT and GO groups. The metabolisms of alkanes, lysine,
      octadecadienoic acid and valine was associated with ROS and could be considered
      as new biomarkers of ROS. The nanotoxicological mechanisms involved the
      inhibition of fatty acid, amino acid and small molecule acid metabolisms. These
      findings provide new insights into the effects of GO and C-SWCNT on cellular
      responses. 

PMID- 26295981
TI  - Total Synthesis and Structure Revision of (-)-Siphonodictyal B and Its Biomimetic
      Conversion into (+)-Liphagal.
AB  - The structure of siphonodictyal B has been reassigned on the basis of the total
      synthesis of both possible C-8 epimers. The revised structure of siphonodictyal B
      was converted into liphagal by acid catalyzed rearrangement of a proposed epoxide
      intermediate. This biomimetic cascade features a succession of four distinct
      reactions (epoxidation, o-quinone methide formation, ring expansion, and
      benzofuran formation) that occur in a one-pot operation under mild conditions.
      During these studies we also isolated a surprisingly stable o-quinone methide
      that supports our mechanistic proposal for liphagal biosynthesis. 

PMID- 26295982
TI  - Ovarian and hormonal responses to single or continuous peripheral administration
      of senktide, a neurokinin 3 receptor agonist, during the follicular phase in
      goats.
AB  - The present study aimed to investigate the effects of single or continuous
      administration of a neurokinin 3 receptor agonist, senktide, on hormonal and
      follicular dynamics in follicular phase goats. Goats were injected with PGF2alpha
      in the luteal phase and treated with an intravaginal progesterone device for 10
      d. At 12 h after the cessation of progesterone treatment, the goats received a
      single intravenous injection of senktide (200 nmol, n = 4) or vehicle (n = 4), or
      continuous intravenous infusion of senktide (20 nmol/min, n = 6) or vehicle (n =
      6) for 6 h. Blood sampling and ovarian ultrasonography were performed during the
      experiment. A single injection of senktide did not influence the number of
      luteinizing hormone (LH) pulses and mean LH concentration. On the other hand,
      continuous injection of senktide caused a sustained increase in LH secretion, and
      mean LH concentration in samples collected at 10-min intervals for 6 h after the
      start of infusion was higher than that of vehicle-treated goats (2.8 +/- 1.3 vs
      1.0 +/- 0.6 ng/mL, P < 0.01). In 4 of 6 goats, LH concentrations reached their
      peaks during the 6-h senktide infusion, and ovulation was observed at 48 h after
      the start of infusion without estrous behavior. The remaining 2 senktide-treated
      goats and all vehicle-treated goats showed estrus and ovulated at 72 or 96 h
      after treatment. These results suggest that continuous infusion of senktide in
      follicular phase goats can cause a sustained increase in LH and advance the time
      of ovulation. 

PMID- 26295983
TI  - Laboratory developed tests in the clinical laboratory: challenges for
      implementation.

PMID- 26295984
TI  - Hematocrit-independent recovery is a key for bioanalysis using volumetric
      absorptive microsampling devices, MitraTM.
AB  - BACKGROUND: A novel microsampling device, Mitra(TM), was evaluated for
      bioanalysis of E6005 and its O-desmethylated metabolite in human whole blood
      using an UPLC-MS. RESULTS: A constant volume of blood samples was absorbed onto
      the tip of Mitra, the analytes were extracted by various solvents and then
      detected by UPLC-MS. Recovery of the analytes was high in acetonitrile-water
      (1:1, v/v) but was dependent on hematocrit (Hct) without sonication process,
      which led to biased accuracy at low and high Hcts. Inclusion of sonication
      process in extraction improved recovery at high Hct to yield acceptable accuracy
      across Hcts. CONCLUSION: Optimization of extraction process to achieve high
      recovery regardless of Hct is critical in accurate bioanalysis via Mitra.

PMID- 26295985
TI  - HPLC-MS/MS method to measure trabectedin in tumors: preliminary PK study in a
      mesothelioma xenograft model.
AB  - BACKGROUND: Trabectedin is an anticancer agent registered for the second-line
      treatment of soft tissue sarcoma and ovarian cancer. No preclinical data are
      available on its tumor distribution, so a method for quantification in neoplastic
      tissues is required. METHODS/RESULTS: We validated an LC-MS/MS assay determining
      the recovery, sensitivity, linearity, precision and accuracy in mouse tumor and
      liver samples. The limit of quantification was 0.10 ng/ml with a curve range of
      0.10-3.00 ng/ml (accuracy 96.1-102.1%). Inter-day precision and accuracy of QCs
      were 6.0-8.2 and 97.0-102.6% respectively. The method was applied in mesothelioma
      xenografts treated with therapeutic doses. CONCLUSION: The method was validated
      for measuring trabectedin in tissues. In a mesothelioma xenograft model,
      trabectedin distributed preferentially in tumor compared with liver.

PMID- 26295987
TI  - Simultaneous determination of hyzetimibe and its main active metabolite in plasma
      by LC-MS/MS and its application in PK study.
AB  - BACKGROUND: Hyzetimibe is a new compound belonging to a novel class of selective
      cholesterol absorption inhibitors. A simple, highly sensitive LC-MS/MS method has
      been developed for the quantification of hyzetimibe and its main active
      metabolite, hyzetimibe-glucuronide, in human plasma. RESULTS: Analytical samples
      were prepared using a protein precipitation method coupled with a concentration
      process. The linearity of this method was established for concentrations in the
      ranges of 0.05-50 and 0.5-500 ng/ml for hyzetimibe and hyzetimibe-glucuronide,
      respectively. The accuracy and precision of the method varied from 97.9 to 105%
      and 2.6 to 7.4%, respectively. CONCLUSION: This study represents the first
      reported example of an LC-MS/MS assay for the simultaneous quantification of
      hyzetimibe and its main active metabolite, hyzetimibe-glucuronide, in human
      plasma. Furthermore, this method has been successfully applied to a PK study.

PMID- 26295988
TI  - Development and characterization of antibody reagents to assess anti-PEG IgG
      antibodies in clinical samples.
AB  - BACKGROUND: Polyethylene glycol (PEG) is a polymer that can be conjugated with
      therapeutic proteins. Monitoring anti-PEG antibodies in human subjects may be
      required as part of immunogenicity assessment. The lack of well-characterized
      anti-PEG reagents have limited our understanding of anti-PEG humoral response.
      RESULTS: Antibodies reactive to PEG were engineered with a human IgG1 Fc. Surface
      plasmon resonance and plate-based methods demonstrated that their binding was
      dependent on molecular weight (MW) of PEG. Specificity experiments using chemical
      analogs identified their specificity. CONCLUSION: Affinity, specificity and MW of
      PEG are critical characteristics that impact interactions of anti-PEG antibodies
      with PEG. These attributes especially MW of PEG and the assay formats may impact
      the ability to detect anti-PEG antibodies.

PMID- 26295986
TI  - Stable isotopes and LC-MS for monitoring metabolic disturbances in Friedreich's
      ataxia platelets.
AB  - BACKGROUND: Friedreich's ataxia (FRDA) is an autosomal recessive disease with
      metabolic abnormalities that have been proposed to play an important role in the
      resulting neurodegeneration and cardiomyopathy. The inability to access the
      highly affected neuronal and cardiac tissues has hampered metabolic evaluation
      and biomarker development. METHODS: Employment of a LC-MS-based method to
      determine whether platelets isolated from patients with FRDA exhibit
      differentiable metabolism compared with healthy controls. RESULTS: Isotopologue
      analysis showed a marked decrease in glucose incorporation with a concomitant
      increase in palmitate-derived acyl-CoA thioesters in FRDA platelets compared with
      controls. CONCLUSION: Our findings demonstrate that platelets can be used as a
      surrogate tissue for in vivo biomarker studies to monitor new therapeutic
      approaches for the treatment of FRDA.

PMID- 26295989
TI  - Thermal inactivation of enzymes and pathogens in biosamples for MS analysis.
AB  - Protein denaturation is the common basis for enzyme inactivation and inactivation
      of pathogens, necessary for preservation and safe handling of biosamples for
      downstream analysis. While heat-stabilization technology has been used in
      proteomic and peptidomic research since its introduction in 2009, the advantages
      of using the technique for simultaneous pathogen inactivation have only recently
      been addressed. The time required for enzyme inactivation by heat (~1 min) is
      short compared with chemical treatments, and inactivation is irreversible in
      contrast to freezing. Heat stabilization thus facilitates mass spectrometric
      studies of biomolecules with a fast conversion rate, and expands the chemical
      space of potential biomarkers to include more short-lived entities, such as
      phosphorylated proteins, in tissue samples as well as whole-blood (dried blood
      sample) samples. 

PMID- 26295990
TI  - Ambient ionization MS for bioanalysis: recent developments and challenges.
AB  - Ambient ionization MS has become very popular in analytical science and has now
      evolved as an effective analytical tool in metabolomics, biological tissue
      imaging, protein and small molecule drug analysis, where biological samples are
      probed in a rapid and direct fashion with minimal sample preparation at ambient
      conditions. However, certain inherent challenges continue to hinder the vibrant
      prospects of these methods for in situ analyses or to replace conventional
      methods in bioanalysis. This review provides an introduction to the field and its
      application in bioanalysis, with an emphasis on the most recent developments and
      applications. Furthermore, ongoing challenges or limitations related to
      quantitation, sensitivity, selectivity, instrumentation and mass range of these
      ambient methods will also be discussed. 

PMID- 26295991
TI  - Current advances in biosampling for therapeutic drug monitoring of psychiatric
      CNS drugs.
AB  - Many CNS drugs are effective for the treatment of psychiatric disorders.
      Psychotropic drugs work differently, thus clinical outcomes for many patients may
      be insufficient. For this reason it could be useful the measurement of drug
      levels for clinical decision-making. Analytical goals in therapeutic drug
      monitoring (TDM) should be established by selecting the appropriate biological
      matrix. The aim of this review is to highlight the usefulness of TDM for
      antiepileptics, antidepressants and antipsychotics, with a focus on current
      advances in biosampling. The literature on TDM was reviewed up to March 2015. An
      overview on the use of alternative biological matrices is provided to address the
      current issues and advances in the field of biosampling for psychiatric CNS drug
      TDM. 

PMID- 26295992
TI  - LC-MS-based quantification of intact proteins: perspective for clinical and
      bioanalytical applications.
AB  - Bioanalytical LC-MS for protein quantification is traditionally based on
      enzymatic digestion of the target protein followed by absolute quantification of
      a specific signature peptide relative to a stable-isotope labeled analog. The
      enzymatic digestion, nonetheless, limits rapid method development, sample
      throughput and turnaround time, and, moreover, makes that essential information
      regarding the biological function of the intact protein is lost. The recent
      advancements in high-resolution MS instrumentation and improved sample
      preparation techniques dedicated to protein clean-up raise the question to what
      extent LC-MS can be applied for quantitative bioanalysis of intact proteins. This
      review provides an overview of current and potential applications of LC-MS for
      intact protein quantification as well as the main limitations and challenges for
      broad application. 

PMID- 26295994
TI  - I. Nutritional Requirements of Extremely-Low-Birth-Weight Preterm Infants.

PMID- 26295995
TI  - VIII. Human Milk Banks: How to Organize the Collection of Human Milk to Feed
      Preterm Infants.

PMID- 26295996
TI  - IX. Effect of A Human Milk Bank on Breast-feeding Rate in Very-Low-Birth-Weight
      Infants.

PMID- 26295997
TI  - X. Centralized Breast Milk Handling and Bar Code Scanning Improve Patient Safety.

PMID- 26295998
TI  - XI. Relationship Between Feeding and Early Stress in Premature Infant: The Role
      of Epigenetic Factors.

PMID- 26295999
TI  - XII. Human Milk in Feeding Premature Infants: Consensus Statement.

PMID- 26296000
TI  - II. Advantages of Human Milk in Feeding Premature Infants.

PMID- 26296001
TI  - III. Individualized Fortification of Human Milk: Targeted Fortification.

PMID- 26296002
TI  - IV. Individualized Fortification of Human Milk: Adjustable Fortification.

PMID- 26296003
TI  - V. Processing of Donor Human Milk.

PMID- 26296004
TI  - VI. Bioengineering Human Milk: Why?

PMID- 26296005
TI  - VII. Fortification of Human Milk With Human Milk Components.

PMID- 26296006
TI  - Liquid marble and water droplet interactions and stability.
AB  - The interactions between two individual water droplets were investigated in air
      using a combination of coalescence rig and high speed video camera. This
      combination allows the visualization of droplet coalescence dynamics with
      millisecond resolution which provides information on droplet stability. Bare
      water droplets coalesced rapidly upon contact, while droplet stability was
      achieved by coating the droplets with polystyrene particles carrying pH
      responsive poly[2-(diethylamino)ethyl methacrylate] hairs (PDEA-PS particles) to
      form liquid marbles. The asymmetric interaction of a water droplet (pH 3 or 10)
      armoured with the PDEA-PS particles (liquid marble) with a bare droplet at pH 3
      exhibited intermediate stability with coalescence observed following an induction
      time. The induction time was longer for the pH 10 liquid marble, where the PDEA
      PS particles have a hydrophobic surface, than in the case of a pH 3 liquid
      marble, where the PDEA-PS particles have a hydrophilic surface. Furthermore, film
      formation of PDEA-PS particles on the liquid marble surface with toluene vapour
      confirmed capsule formation which prevented coalescence with the neighbouring
      water droplet instead wetting the capsule upon contact within 3 milliseconds.
      This study illuminates the stability of individual particle-stabilized droplets
      and has potential impact on processes and formulations which involve their
      interaction. 

PMID- 26296007
TI  - Internet Pornography Use, Body Ideals, and Sexual Self-Esteem in Norwegian Gay
      and Bisexual Men.
AB  - The purpose of this study was to explore the relationship between perception of
      own appearance, Internet pornography consumption, preferences for pornographic
      actors' appearance, and sexual self-esteem in gay and bisexual men in Norway. An
      online survey of 477 gay and bisexual men showed that, despite the prevailing
      muscular and lean gay body ideal, many men with less ideal bodies also preferred
      to watch pornographic actors with body types similar to their own. Self-perceived
      attractiveness, having an ideal body type, and viewing Internet pornography in
      longer sessions each made a unique contribution to higher self-esteem as a sexual
      partner. Preferring to watch pornographic actors with ideal bodies was not
      related to sexual self-esteem. The findings underscore the importance for gay or
      bisexual men of both self-perceived attractiveness and being athletic or young
      and fit, for a positive self-evaluation of sexual performance and competence. 

PMID- 26296009
TI  - DPD Simulation of Protein Conformations: From alpha-Helices to beta-Structures.
AB  - We suggest a coarse-grained model for DPD simulations of polypeptides in
      solutions. The model mimics hydrogen bonding that stabilizes alpha-helical and
      beta-structures using dissociable Morse bonds between quasiparticles representing
      the peptide groups amenable to hydrogen bonding. We demonstrate the capabilities
      of the model by simulating transitions between coil-like, globular, alpha
      helical, and beta-hairpin configurations of model peptides, varying Morse
      potential parameters, the hydrophobicities of residue side chains, and pH, which
      determines the charges of residue side chains. We construct a model triblock
      polypeptide mimicking the sequence of residues alpha-synuclein at two different
      pHs. The conformations of this model polypeptide depend on pH similarly to the
      behavior observed experimentally. The suggested approach to accounting for
      hydrogen bond formation within the general DPD framework may make the DPD method
      a competitive alternative to CGMD for modeling equilibrium and dynamic properties
      of proteins and polypeptides, especially during their transport in confined
      environments. 

PMID- 26296010
TI  - Getting your Submission Right and Avoiding Rejection.

PMID- 26296011
TI  - Femtosecond Intersystem Crossing in the DNA Nucleobase Cytosine.
AB  - Ab initio molecular dynamics including nonadiabatic and spin-orbit couplings on
      equal footing is used to unravel the deactivation of cytosine after UV light
      absorption. Intersystem crossing (ISC) is found to compete directly with internal
      conversion in tens of femtoseconds, thus making cytosine the organic compound
      with the fastest triplet population calculated so far. It is found that close
      degeneracy between singlet and triplet states can more than compensate for very
      small spin-orbit couplings, leading to efficient ISC. The femtosecond nature of
      the ISC process highlights its importance in photochemistry and challenges the
      conventional view that large singlet-triplet couplings are required for an
      efficient population flow into triplet states. These findings are important to
      understand DNA photostability and the photochemistry and dynamics of organic
      molecules in general. 

PMID- 26296012
TI  - Nucleation of Mixed Nitric Acid-Water Ice Nanoparticles in Molecular Beams that
      Starts with a HNO3 Molecule.
AB  - Mixed (HNO3)m(H2O)n clusters generated in supersonic expansion of nitric acid
      vapor are investigated in two different experiments, (1) time-of-flight mass
      spectrometry after electron ionization and (2) Na doping and photoionization.
      This combination of complementary methods reveals that only clusters containing
      at least one acid molecule are generated, that is, the acid molecule serves as
      the nucleation center in the expansion. The experiments also suggest that at
      least four water molecules are needed for HNO3 acidic dissociation. The clusters
      are undoubtedly generated, as proved by electron ionization; however, they are
      not detected by the Na doping due to a fast charge-transfer reaction between the
      Na atom and HNO3. This points to limitations of the Na doping recently advocated
      as a general method for atmospheric aerosol detection. On the other hand, the
      combination of the two methods introduces a tool for detecting molecules with
      sizable electron affinity in clusters. 

PMID- 26296013
TI  - Dry Deposition of Biogenic Terpenes via Cationic Oligomerization on Environmental
      Aqueous Surfaces.
AB  - Unraveling the complex interactions between the atmosphere and the biosphere is
      critical for predicting climate changes. Although it is well-recognized that the
      large amounts of biogenic volatile organic compounds (BVOCs) emitted by plants
      must play important roles in this regard, current atmospheric models fail to
      account for their fate due to missing chemical sinks. Here, we applied online
      electrospray mass spectrometry to monitor aqueous microjets exposed to gaseous
      monoterpenes (alpha-pinene, beta-pinene, and d-limonene) and found that these
      BVOCs are readily protonated (to C10H17(+)) and undergo oligomerization (to
      C20H33(+) and C30H49(+)) upon colliding with the surface of pH < 4 microjets. By
      considering that the yields of all products show inflection points at pH ~ 3.5
      and display solvent kinetic hydrogen isotope effects larger than 2, we conclude
      that the oligomerization process is initiated by weakly hydrated hydronium ions,
      H3O(+), present at the gas-water interface. Present results provide a universal
      mechanism for the dry deposition of unsaturated BVOCs and may account for recent
      observations on the uptake of terpenes in forest canopies and over grassland. 

PMID- 26296014
TI  - Strain-Induced Spin Crossover in Phthalocyanine-Based Organometallic Sheets.
AB  - Motivated by the recent success in synthesizing two-dimensional Fe-phthalocyanine
      (poly-FePc) porous sheets, we studied strain-induced spin crossover in poly-TMPc
      (TM = Mn, Fe, Co, and Ni) systems by using first-principle calculations based on
      density functional theory. A small amount of biaxial tensile strain is found to
      not only significantly enhance the magnetic moment of the central TM atoms by 2
      MUB when the strain reaches a critical value, but also the systems undergo low
      spin (LS) to high-spin (HS) transition. These systems, however, show different
      response to strain, namely, poly-FePc sheet becomes ferromagnetic (FM) while poly
      MnPc and poly-NiPc sheets become antiferromagnetic (AFM). Poly-CoPc, on the other
      hand, remains AFM. These predicted results can be observed in suspended poly-TMPc
      sheets by using scanning tunneling microscope (STM) tips to manipulate strain. 

PMID- 26296015
TI  - Modulation of Visible Room Temperature Phosphorescence by Weak Magnetic Fields.
AB  - Magnetic control over excited states of molecules presents interest for many
      applications. Here we show for the first time that visible room temperature
      phosphorescence in multichromophoric donor-acceptor systems can be modulated by
      weak magnetic fields (<1 T) via magnetic field effects (MFE) on the spin dynamics
      in photogenerated radical pairs (RPs). The studied compounds comprise Pt
      porphyrin (PtP)-Rosamine B (RosB) dyads, which possess strong visible absorption
      bands and phosphoresce at room temperature. The observed MFE is unique in that it
      occurs upon direct excitation of the PtP in the dyads, whereby ultrafast
      quantitative formation of the local PtP triplet state precedes the occurrence of
      radical intermediates. A model explaining the effect is proposed, which is based
      on reversible electron transfer between the local triplet state and a long-lived
      RP. External magnetic field modulates spin dynamics in the RP, affecting
      contribution of the singlet RP recombination channel and thereby influencing
      phosphorescence. 

PMID- 26296016
TI  - Insights into Li(+) Migration Pathways in alpha-Li3VF6: A First-Principles
      Investigation.
AB  - Magnetic, structural, and defect properties of lithium vanadium hexafluoride
      (alpha-Li3VF6) are investigated theoretically with periodic quantum chemical
      methods. It is found that the ferromagnetic phase is more stable than the
      antiferromagnetic phase. The crystal structure contains three inequivalent Li
      sites (Li(1), Li(2), and Li(3)), where Li(1) occupies the middle position of the
      triplet Li(2)-Li(1)-Li(3). The calculated Li vacancy formation energies show that
      vacancy formation is preferred for the Li(1) and Li(3) sites compared to the
      Li(2) position. The Li exchange processes between Li(1) <-> Li(3), Li(1) <->
      Li(2), and Li(2) <-> Li(3) are studied by calculating the Li(+) migration between
      these sites using the climbing-image nudged elastic band approach. It is observed
      that Li exchange in alpha-Li3VF6 may take place in the following order: Li(1) <->
      Li(3) > (Li(1) <-> Li(2) > Li(2) <-> Li(3). This is in agreement with recently
      published results obtained from 1D and 2D (6)Li exchange nuclear magnetic
      resonance spectroscopy. 

PMID- 26296017
TI  - Excited States in Cycloparaphenylenes: Dependence of Optical Properties on Ring
      Length.
AB  - Hoop-shaped conjugated molecules, cycloparaphenylenes (CPPs), are simple strings
      of benzene rings with para linkages that have an ideal quasi-one-dimensional
      structure without edges. Here, we report optical properties of [n]CPPs (n = 9,
      12, 14, 15, 16) clarified by one- and two-photon excitation spectroscopy. We
      showed that in this system the lowest unoccupied molecular orbital (LUMO) state
      has the same symmetry as the highest occupied molecular orbital (HOMO) state, and
      determined the transition energy of the optically forbidden HOMO-LUMO gap. It is
      found that the ring-length dependence of the HOMO-LUMO transition energy is
      identical to that of the photoluminescence (PL) energy, and that phonon-assisted
      transition causes efficient PL. 

PMID- 26296018
TI  - Entanglement Measures for Single- and Multireference Correlation Effects.
AB  - Electron correlation effects are essential for an accurate ab initio description
      of molecules. A quantitative a priori knowledge of the single- or multireference
      nature of electronic structures as well as of the dominant contributions to the
      correlation energy can facilitate the decision regarding the optimum quantum
      chemical method of choice. We propose concepts from quantum information theory as
      orbital entanglement measures that allow us to evaluate the single- and
      multireference character of any molecular structure in a given orbital basis set.
      By studying these measures we can detect possible artifacts of small active
      spaces. 

PMID- 26296019
TI  - Coherent Energy Transfer under Incoherent Light Conditions.
AB  - Recent two-dimensional electronic spectroscopy (2DES) experiments have reported
      evidence of coherent dynamics of electronic excitations in several light
      harvesting antennae. However, 2DES uses ultrafast coherent laser pulses as an
      excitation source; therefore, there is a current debate on whether coherent
      excitation dynamics is present under natural sunlight - incoherent - illumination
      conditions. In this letter, we show that even if incoherent light excites an
      electronic state with no initial quantum superpositions among excitonic states,
      energy transfer can proceed quantum coherently if nonequilibrium dynamics of the
      phonon environment takes place. Such nonequilibrium behavior manifests itself in
      non-Markovian evolution of electronic excitations and is typical of many
      photosynthetic systems. We therefore argue that light-harvesting antennae have
      mechanisms that could support coherent evolution under incoherent illumination. 

PMID- 26296020
TI  - Predicted Optimum Composition for the Glass-Forming Ability of Bulk Amorphous
      Alloys: Application to Cu-Zr-Al.
AB  - Metallic glasses have been established to have unique properties such as
      ductility, toughness, and soft magnetism with promising engineering applications.
      However, the glass-forming ability (GFA) has not been sufficient to synthesize
      the bulk metallic glasses (BMGs) required for many engineering applications.
      Attempts to develop the understanding of the GFA required to predict the optimum
      alloys have not yet been proven successful. We develop here a computational model
      based on molecular dynamics simulations that explains the dramatic change of GFA
      with alloying small amounts of Al into Cu-Zr. We find that the high GFA to form
      BMGs depends on a combination of three factors, (a) a low thermodynamic driving
      force for crystallization, (b) a high melt viscosity, and (c) large ratios of
      icosahedral structures in the liquid phase. These computational methods to
      predict these factors that suppress formation of crystal nuclei and slow the
      dynamic motions in the liquids are practical for in silico prediction of new
      alloys with optimal GFA. 

PMID- 26296021
TI  - Engineering Nanomaterials for Biomedical Applications Requires Understanding the
      Nano-Bio Interface: A Perspective.
AB  - The promise of nanobiomaterials for diagnostic and therapeutic biomedical
      applications has been widely reported throughout the scientific community, and
      great strides have been made in those directions. And yet, the translation of
      nanomaterial-based therapeutics to clinical applications remains an elusive
      target. Many challenges have blocked the usage of nanomaterials in biomedicine,
      including potential toxicity, immunogenicity, and decreased efficacy. In order to
      overcome some of these issues, detailed studies have been undertaken to
      understand fundamental interactions between nanomaterials and the biological
      environment. In particular, recent developments in nanoparticle synthesis, a
      better understanding and control over nanoparticle surface chemistry, as well as
      the organization of that chemistry on the nanoparticle surface, has allowed
      researchers to begin to understand how spatial arrangement of atomic and
      molecular species at an interface can affect protein adsorption, structure, and
      subsequent biological outcomes. This perspective strives to identify ways in
      which the nanomaterial interface can be controlled to affect interactions with
      biomolecules for beneficial biomedical applications. 

PMID- 26296022
TI  - Correction to "Understanding Periodic Dislocations in 2D Supramolecular Crystals:
      The PFP/Ag(111) Interface".

PMID- 26296023
TI  - Mid- and Far-IR Spectra of H5(+) and D5(+) Compared to the Predictions of
      Anharmonic Theory.
AB  - H5(+) is the smallest proton-bound dimer. As such, its potential energy surface
      and spectroscopy are highly complex, with extreme anharmonicity and vibrational
      state mixing; this system provides an important benchmark for modern theoretical
      methods. Unfortunately, previous measurements covered only the higher-frequency
      region of the infrared spectrum. Here, spectra for H5(+) and D5(+) are extended
      to the mid- and far-IR, where the fundamental of the proton stretch and its
      combinations with other low-frequency vibrations are expected. Ions in a
      supersonic molecular beam are mass-selected and studied with multiple-photon
      dissociation spectroscopy using the FELIX free electron laser. A transition at
      379 cm(-1) is assigned tentatively to the fundamental of the proton stretch of
      H5(+), and bands throughout the 300-2200 cm(-1) region are assigned to
      combinations of this mode with bending and torsional vibrations. Coupled
      vibrational calculations, using ab initio potential and dipole moment surfaces,
      account for the highly anharmonic nature of these complexes. 

PMID- 26296024
TI  - Tuning the Luminescence Properties of Colloidal I-III-VI Semiconductor
      Nanocrystals for Optoelectronics and Biotechnology Applications.
AB  - In the past 5 years, colloidal I-III-VI nanocrystals such as CuInS2, CuInSe2, and
      AgInS2 have been intensively investigated for the potential to replace commonly
      available colloidal nanocrystals containing toxic elements in light-emitting and
      solar-harvesting applications. Many researchers from different disciplines are
      working on developing new synthetic protocols, performing spectroscopic studies
      to understand the luminescence mechanisms, and exploring various applications. To
      achieve enhanced performance, it is very desirable to obtain high-quality
      materials with tunable luminescence properties. In this Perspective, we highlight
      the current progress on tuning the luminescence properties of I-III-VI
      nanocrystals, especially focusing on the advances in the synthesis, spectroscopic
      properties, as well as the primary applications in light-emitting devices and
      bioimaging techniques. Finally, we outline the challenges concerning luminescent
      I-III-VI NCs and list a few important research tasks in this field. 

PMID- 26296025
TI  - Exploiting In Situ Solid-State NMR for the Discovery of New Polymorphs during
      Crystallization Processes.
AB  - We report the discovery of new polymorphic forms of solids by exploiting a solid
      state NMR technique that has been developed for in situ monitoring of the
      evolution of crystallization processes. The capability of the technique to reveal
      the existence of new polymorphic forms of molecular solids is illustrated by the
      discovery of two new polymorphs of methyldiphenylphosphine oxide and a new solid
      form of the 1,10-dihydroxydecane/urea system. 

PMID- 26296026
TI  - Active Surface Oxygen for Catalytic CO Oxidation on Pd(100) Proceeding under Near
      Ambient Pressure Conditions.
AB  - Catalytic CO oxidation reaction on a Pd(100) single-crystal surface under several
      hundred mTorr pressure conditions has been studied by ambient pressure X-ray
      photoelectron spectroscopy and mass spectroscopy. In-situ observation of the
      reaction reveals that two reaction pathways switch over alternatively depending
      on the surface temperature. At lower temperatures, the Pd(100) surface is covered
      by CO molecules and the CO2 formation rate is low, indicating CO poisoning. At
      higher temperatures above 190  degrees C, an O-Pd-O trilayer surface oxide phase
      is formed on the surface and the CO2 formation rate drastically increases. It is
      likely that the enhanced rate of CO2 formation is associated with an active
      oxygen species that is located at the surface of the trilayer oxide. 

PMID- 26296027
TI  - Improving Hematite's Solar Water Splitting Efficiency by Incorporating Rare-Earth
      Upconversion Nanomaterials.
AB  - Confounded by global energy needs, much research has been devoted to convert
      solar energy to various usable forms, such as chemical energy in the form of
      hydrogen via water splitting. Most photoelectrodes, such as hematite, utilize UV
      and visible radiation, whereas ~40% infrared (IR) energy remains unconverted.
      This work represents our initial attempt to utilize IR radiation, that is, adding
      rare-earth materials to existing photoelectrodes. A simple substrate composed of
      hematite film and rare-earth nanocrystals (RENs) was prepared and characterized.
      Spectroscopy evidence indicates that the RENs in the composite absorb IR
      radiation (980 nm) and emit at 550 and 670 nm. The emitted photons are absorbed
      by surrounding hematite films, leading to improvement of water splitting
      efficiency as measured by photocurrent enhancement. This initial work
      demonstrates the feasibility and concept of using RENs for utilizing more solar
      radiation, thus improving the efficiency of existing solar materials and devices.

PMID- 26296028
TI  - Reaction Probability and Infrared Detection of the Primary Ozonide in Collisions
      of O3 with Surface-Bound C60.
AB  - The kinetics and mechanism of reactions between gas-phase ozone and surface-bound
      C60 have been investigated by monitoring changes to reflection-absorption
      infrared spectra within a well-characterized film of C60 during exposure to a
      controlled flux of pure ozone. These ultrahigh vacuum studies provide direct
      infrared spectroscopic evidence for the formation and decomposition of a primary
      ozonide of C60. The spectral assignments of this highly unstable intermediate
      have been verified using electronic structure calculations. Theory and experiment
      revealed that C60 oxidized nearly exclusively via addition of ozone across the
      double bond that links two six-carbon-containing rings of the molecule. Following
      spectral characterization, the initial probability for ozone to react with the
      surface was found to be 5.8 +/- 0.2 * 10(-4). Once formed, the ozonide quickly
      thermally decomposed to a variety of carbonyl-containing products. 

PMID- 26296029
TI  - Characterizing Charge Transfer at Water Ice Interfaces.
AB  - Simulations are carried out for the ice/vapor and ice/liquid interfaces using
      models for water which include intermolecular charge transfer, as well as
      polarizability. The models transfer a small amount of charge for each hydrogen
      bond formed, as indicated from electronic structure calculations, from the
      molecule that accepts the hydrogen bond to the molecule that donates the hydrogen
      bond. Depending on distance from the interface, molecules can, on average, have
      more of one type (donor or acceptor) than the other. The asymmetric local
      environment leads to net charge transfer at the interface, with layers of
      molecules with small net charges. Molecules at the ice side of the interface tend
      to be positively charged, while molecules at the vapor or liquid side tend to be
      negatively charged. 

PMID- 26296030
TI  - pH-Response Mechanism of p-Aminobenzenethiol on Ag Nanoparticles Revealed By Two
      Dimensional Correlation Surface-Enhanced Raman Scattering Spectroscopy.
AB  - The existence of pH-dependent surface-enhanced Raman scattering (SERS) of p
      aminobenzenethiol (PATP) on Ag nanoparticles has been confirmed by numerous
      studies, but its mechanism still remains to be clarified. Discussion of the
      mechanism is at a standstill because of the lack of a systematic investigation of
      the process behind the pH-induced variation of the PATP behavior. Two-dimensional
      correlation spectroscopy is one of the most powerful and versatile spectral
      analysis methods for investigating perturbation-induced variations in dynamic
      data. Herein, we have analyzed the pH-dependent behavior of PATP using a static
      buffer solution with pH ranging from 3.0 to 2.0. The order of the variations in
      the different vibrational intensities was carefully investigated based on 2D
      correlation SERS spectroscopy. These results have demonstrated that the very
      first step of the pH-response process involves protonation of the amine group.
      The pH-response mechanism revealed is an important new component to our
      understanding of the origin of the b2-type bands of PATP. 

PMID- 26296031
TI  - Real-Time XRD Studies of Li-O2 Electrochemical Reaction in Nonaqueous Lithium
      Oxygen Battery.
AB  - Understanding of electrochemical process in rechargeable Li-O2 battery has
      suffered from lack of proper analytical tool, especially related to the
      identification of chemical species and number of electrons involved in the
      discharge/recharge process. Here we present a simple and straightforward
      analytical method for simultaneously attaining chemical and quantified
      information of Li2O2 (discharge product) and byproducts using in situ XRD
      measurement. By real-time monitoring of solid-state Li2O2 peak area, the accurate
      efficiency of Li2O2 formation and the number of electrons can be evaluated during
      full discharge. Furthermore, by observation of sequential area change of Li2O2
      peak during recharge, we found nonlinearity of Li2O2 decomposition rate for the
      first time in ether-based electrolyte. 

PMID- 26296032
TI  - X-ray Birefringence: A New Strategy for Determining Molecular Orientation in
      Materials.
AB  - While the phenomenon of birefringence is well-established in the case of visible
      radiation and is exploited in many fields (e.g., through the use of the
      polarizing optical microscope), the analogous phenomenon for X-rays has been a
      virtually neglected topic. Here, we demonstrate the scope and potential for
      exploiting X-ray birefringence to determine the orientational properties of
      specific types of bonds in solids. Specifically, orientational characteristics of
      C-Br bonds in the bromocyclohexane/thiourea inclusion compound are elucidated
      from X-ray birefringence measurements at energies close to the bromine K-edge,
      revealing inter alia the changes in the orientational distribution of the C-Br
      bonds associated with a low-temperature order-disorder phase transition. From
      fitting a theoretical model to the experimental data, reliable quantitative
      information on the orientational properties of the C-Br bonds is determined. The
      experimental strategy reported here represents the basis of a new approach for
      gaining insights into the orientational properties of molecules in anisotropic
      materials. 

PMID- 26296033
TI  - Crossing Electronic States in the Franck-Condon Zone of Carbon Dioxide: A Five
      Fold Closed Seam of Conical and Glancing Intersections.
AB  - Intersections of electronic states are recognized as natural molecular hubs
      routing initial photoexcitation toward specific products. In this Letter, we
      investigate a five-fold intersection between the 2,3(1)A' and 1,2,3(1)A"
      electronic states of CO2 responsible for the ultraviolet absorption of the
      molecule between 120 and 160 nm. It is demonstrated that the intersection is not
      an isolated point but a seam with the following properties: (1) The seam
      comprises both conical and glancing intersections. (2) The seam is a closed loop
      traced by the concerted displacements of two CO bonds. (3) The seam is
      constrained to linear geometries and confined to the CO bond plane. (4) The seam
      passes directly through the Franck-Condon zone. Topography and properties of the
      intersection seam are validated using assignment of the electronic wave functions
      and illustrated using circulation of the derivative couplings along closed
      contours. The possibility of observation of strongly curved seams is briefly
      discussed. 

PMID- 26296034
TI  - Evaporation-Induced Crumpling of Graphene Oxide Nanosheets in Aerosolized
      Droplets: Confinement Force Relationship.
AB  - A possible solution to solve the restacking issue of graphene oxide (GO)
      nanosheets during large-scale production is to turn the two-dimensional (2D)
      nanosheets into three-dimensional (3D) crumpled balls that have excellent
      compressive properties but still maintain high free volumes. An aerosol-based
      process has been proven to be a rational method for this purpose, in which, the
      crumpling phenomenon, however, has hitherto remained unclear. Here we present a
      detailed understanding of the crumpling of GO nanosheets by a systematic
      investigation conducted in aerosolized droplets by means of in-line (e.g.,
      scanning mobility particle sizer) and off-line (e.g., electron microscopy)
      measurements. Correlations between the confinement force and various parameters,
      such as evaporation rate and precursor concentration were established to derive a
      universally applicable equation. Both calculation and experimental results
      revealed that the evaporation rate plays an important role in controlling the
      crumpling process. 

PMID- 26296035
TI  - Photocatalytic Hydrogen Generation Efficiencies in One-Dimensional CdSe
      Heterostructures.
AB  - To better understand the role nanoscale heterojunctions play in the
      photocatalytic generation of hydrogen, we have designed several model one
      dimensional (1D) heterostructures based on CdSe nanowires (NWs). Specifically,
      CdSe/CdS core/shell NWs and Au nanoparticle (NP)-decorated core and core/shell
      NWs have been produced using facile solution chemistries. These systems enable us
      to explore sources for efficient charge separation and enhanced carrier lifetimes
      important to photocatalytic processes. We find that visible light H2 generation
      efficiencies in the produced hybrid 1D structures increase in the order CdSe <
      CdSe/Au NP < CdSe/CdS/Au NP < CdSe/CdS with a maximum H2 generation rate of 58.06
      +/- 3.59 MUmol h(-1) g(-1) for CdSe/CdS core/shell NWs. This is 30 times larger
      than the activity of bare CdSe NWs. Using femtosecond transient differential
      absorption spectroscopy, we subsequently provide mechanistic insight into the
      role nanoscale heterojunctions play by directly monitoring charge flow and
      accumulation in these hybrid systems. In turn, we explain the observed trend in
      H2 generation rates with an important outcome being direct evidence for
      heterojunction-influenced charge transfer enhancements of relevant chemical
      reduction processes. 

PMID- 26296036
TI  - The role of mast cells in AIN: friend, foe, bystander, or all of the above?

PMID- 26296037
TI  - NephroPharmacology coming of age.

PMID- 26296038
TI  - A Tale of Copper Coordination Frameworks: Controlled Single-Crystal-to-Single
      Crystal Transformations and Their Catalytic C-H Bond Activation Properties.
AB  - Metal-organic frameworks (MOFs), as a class of microporous materials with well
      defined channels and rich functionalities, hold great promise for various
      applications. Yet the formation and crystallization processes of various MOFs
      with distinct topology, connectivity, and properties remain largely unclear, and
      the control of such processes is rather challenging. Starting from a 0D Cu
      coordination polyhedron, MOP-1, we successfully unfolded it to give a new 1D-MOF
      by a single-crystal-to-single-crystal (SCSC) transformation process at room
      temperature as confirmed by SXRD. We also monitored the continuous transformation
      states by FTIR and PXRD. Cu MOFs with 2D and 3D networks were also obtained from
      this 1D-MOF by SCSC transformations. Furthermore, Cu MOFs with 0D, 1D, and 3D
      networks, MOP-1, 1D-MOF, and HKUST-1, show unique performances in the kinetics of
      the C-H bond catalytic oxidation reaction.

PMID- 26296039
TI  - Fine and gross motor skills: The effects on skill-focused dual-tasks.
AB  - Dual-task methodology often directs participants' attention towards a gross motor
      skill involved in the execution of a skill, but researchers have not investigated
      the comparative effects of attention on fine motor skill tasks. Furthermore,
      there is limited information about participants' subjective perception of
      workload with respect to task performance. To examine this, the current study
      administered the NASA-Task Load Index following a simulated shooting dual-task.
      The task required participants to stand 15 feet from a projector screen which
      depicted virtual targets and fire a modified Glock 17 handgun equipped with an
      infrared laser. Participants performed the primary shooting task alone (control),
      or were also instructed to focus their attention on a gross motor skill relevant
      to task execution (gross skill-focused) and a fine motor skill relevant to task
      execution (fine skill-focused). Results revealed that workload was significantly
      greater during the fine skill-focused task for both skill levels, but performance
      was only affected for the lesser-skilled participants. Shooting performance for
      the lesser-skilled participants was greater during the gross skill-focused
      condition compared to the fine skill-focused condition. Correlational analyses
      also demonstrated a significant negative relationship between shooting
      performance and workload during the gross skill-focused task for the higher
      skilled participants. A discussion of the relationship between skill type,
      workload, skill level, and performance in dual-task paradigms is presented. 

PMID- 26296040
TI  - Semifluorinated Alkane Eye Drops for Treatment of Dry Eye Disease--A Prospective,
      Multicenter Noninterventional Study.
AB  - PURPOSE: Evaporation of the tear film is heavily discussed as one core reason for
      dry eye disease (DED). Subsequently, new artificial tear products are developed
      that specifically target this pathomechanism. Perfluorohexyloctane (F6H8,
      NovaTears((r))) from the family of semifluorinated alkanes is a novel substance
      that has been approved as a medical device, as a nonblurring wetting agent for
      the ocular surface. METHODS: Thirty patients with hyperevaporative dry eye
      received F6H8 during a prospective, multicenter, observational 6-week study.
      Patients were advised to apply 1 drop 4 times daily in both eyes. Parameters
      assessed included best corrected visual acuity, intraocular pressure, Schirmer I
      test, tear fluid, tear film breakup time (TFBUT), corneal staining, meibum
      secretion, and Ocular Surface Disease Index (OSDI((c))). RESULTS: From the 30
      patients recruited, 25 completed the trial per protocol. Four patients
      discontinued F6H8 and 1 patient did not present for follow-up. F6H8 treatment led
      to significant reduction of corneal staining and significant increase of Schirmer
      I and TFBUT. In addition, OSDI score dropped significantly from a mean of 55 (+/-
      23.0) to 34 (+/- 22.4). Visual acuity and ocular pressure did not change.
      CONCLUSIONS: This prospective observational study shows significant beneficial
      effects in patients suffering from evaporative DED, using F6H8 in all the
      relevant parameters tested. The decrease of the OSDI by a mean of 21 points was
      particularly remarkable and clearly exceeds minimal, clinical important
      differences for mild or moderate and severe disease. Overall, F6H8 (NovaTears)
      seems to be safe and effective in treating mild to moderate hyperevaporative DED.

PMID- 26296041
TI  - Health e-mavens: identifying active online health information users.
AB  - BACKGROUND: Given the rapid increase of Internet use for effective health
      communication, it is important for health practitioners to be able to identify
      and mobilize active users of online health information across various web-based
      health intervention programmes. We propose the concept 'health e-mavens' to
      characterize individuals actively engaged in online health information seeking
      and sharing activities. OBJECTIVES: This study aimed to address three goals: (i)
      to test the factor structure of health e-mavenism, (ii) to assess the reliability
      and validity of this construct and (iii) to determine what predictors are
      associated with health e-mavenism. METHODS: This study was a secondary analysis
      of nationally representative data from the 2010 Health Tracking Survey. We
      assessed the factor structure of health e-mavenism using confirmatory factor
      analysis and examined socio-demographic variables, health-related factors and use
      of technology as potential predictors of health e-mavenism through ordered
      regression analysis. RESULTS: Confirmatory factor analyses showed that a second
      order two-factor structure best captured the health e-maven construct. Health e
      mavenism comprised two second-order factors, each encompassing two first-order
      dimensions: information acquisition (consisting of information tracking and
      consulting) and information transmission (consisting of information posting and
      sharing). Both first-order and second-order factors exhibited good reliabilities.
      Several factors were found to be significant predictors of health e-mavenism.
      DISCUSSION AND CONCLUSION: This study offers a starting point for further
      inquiries about health e-mavens. It is a fruitful construct for health promotion
      research in the age of new media technologies. We conclude with specific
      recommendations to further develop the health e-maven concept through continued
      empirical research.

PMID- 26296042
TI  - Engineering human 3D micromuscles with co-culture of fibroblasts and myoblasts.

PMID- 26296044
TI  - Pheochromocytoma: Still an exclusion criterion for Tako-tsubo cardiomyopathy
      diagnosis?

PMID- 26296043
TI  - Anatomical-based partial volume correction for low-dose dedicated cardiac
      SPECT/CT.
AB  - Due to the limited spatial resolution, partial volume effect has been a major
      degrading factor on quantitative accuracy in emission tomography systems. This
      study aims to investigate the performance of several anatomical-based partial
      volume correction (PVC) methods for a dedicated cardiac SPECT/CT system (GE
      Discovery NM/CT 570c) with focused field-of-view over a clinically relevant range
      of high and low count levels for two different radiotracer distributions. These
      PVC methods include perturbation geometry transfer matrix (pGTM), pGTM followed
      by multi-target correction (MTC), pGTM with known concentration in blood pool,
      the former followed by MTC and our newly proposed methods, which perform the MTC
      method iteratively, where the mean values in all regions are estimated and
      updated by the MTC-corrected images each time in the iterative process. The NCAT
      phantom was simulated for cardiovascular imaging with (99m)Tc-tetrofosmin, a
      myocardial perfusion agent, and (99m)Tc-red blood cell (RBC), a pure
      intravascular imaging agent. Images were acquired at six different count levels
      to investigate the performance of PVC methods in both high and low count levels
      for low-dose applications. We performed two large animal in vivo cardiac imaging
      experiments following injection of (99m)Tc-RBC for evaluation of intramyocardial
      blood volume (IMBV). The simulation results showed our proposed iterative methods
      provide superior performance than other existing PVC methods in terms of image
      quality, quantitative accuracy, and reproducibility (standard deviation),
      particularly for low-count data. The iterative approaches are robust for both
      (99m)Tc-tetrofosmin perfusion imaging and (99m)Tc-RBC imaging of IMBV and blood
      pool activity even at low count levels. The animal study results indicated the
      effectiveness of PVC to correct the overestimation of IMBV due to blood pool
      contamination. In conclusion, the iterative PVC methods can achieve more accurate
      quantification, particularly for low count cardiac SPECT studies, typically
      obtained from low-dose protocols, gated studies, and dynamic applications. 

PMID- 26296045
TI  - IgG4-related systemic disease with coronary arteritis and aortitis, causing
      recurring critical coronary ischemia.

PMID- 26296046
TI  - Hemoglobin induces monocyte recruitment and CD163-macrophage polarization in
      abdominal aortic aneurysm.
AB  - BACKGROUND: Increased hemoglobin (Hb) accumulation was reported in abdominal
      aortic aneurysms (AAAs). CD163 is a macrophage receptor involved in tissue Hb
      clearance, however its role in AAA has not been reported. We investigated the
      role of Hb on monocyte recruitment and differentiation towards CD163 expressing
      macrophages ex vivo, in vitro and in human AAA. METHODS AND RESULTS: CD163 mRNA
      and protein expression was significantly higher in human AAA (n=7) vs. healthy
      wall (n=6). CD163 was predominantly found in adventitia of AAA, coinciding with
      areas rich in hemosiderin and adjacent to neoangiogenic microvessels. Dual
      CD14/CD163 expression was observed in recently infiltrated monocytes surrounding
      microvessels. A higher release of soluble CD163 was observed in the conditioned
      medium from AAA (AAA-CM, n=10), mainly in the adventitial layer. Similar to Hb,
      AAA-CM induced CD163-dependent monocyte chemotaxis, especially on circulating
      monocytes from AAA patients. Hb or AAA-CM promoted differentiation towards
      CD163(high)/HLA-DR(low)-expressing macrophages, with enhanced Hb uptake,
      increased anti-inflammatory IL-10 secretion and decreased pro-inflammatory IL
      12p40 release. All these effects were partially suppressed when Hb was removed
      from AAA-CM. Separate analysis on circulating monocytes reported increased
      percentage of pre-infiltrating CD14(++)CD16(+) monocytes in patients with AAA
      (n=21), as compared to controls (n=14). A significant increase in CD163
      expression in CD14(++)CD16(+) monocyte subpopulation was observed in AAA
      patients. CONCLUSIONS: The presence of Hb in the adventitial AAA-wall promotes
      the migration and differentiation of activated circulating monocytes in AAA
      patients, explaining the existence of a protective CD163-macrophage phenotype
      that could take up the Hb present in the AAA-wall, avoiding its injurious
      effects.

PMID- 26296048
TI  - Fatal intracerebral bleeding under rivaroxaban.
AB  - Rivaroxaban is a factor-Xa-inhibitor which has been shown to be non-inferior to
      the vitamin-K-antagonist (VKA) warfarin in atrial fibrillation patients. In the
      manufacturer-sponsored trial, the rate of intracranial hemorrhage in rivaroxaban
      treated patients was lower than in VKA-treated. It is unknown if this advantage
      of rivaroxaban is also present outside clinical trials. We report a patient with
      fatal cerebral bleeding 4months after initiation of rivaroxaban. Bleeding might
      be favored by hypertension, hypoalbuminemia, renal impairment, hepatopathy and
      drug-drug interactions of rivaroxaban with amiodarone and bisoprolol. Patients
      have to be monitored closely after initiation of rivaroxaban, especially if they
      are treated with possibly interacting drugs. Additionally, hepatic function,
      albumin level, and renal function have to be closely monitored. Therapy with VKA
      seems more convenient, safer and more favorable for the patient than rivaroxaban
      with its associated uncertainties concerning metabolization and drug-drug
      interactions and no possibility to reverse its activity in emergency situations. 

PMID- 26296047
TI  - Statins do not increase the risk of developing type 2 diabetes in familial
      hypercholesterolemia: The SAFEHEART study.
AB  - BACKGROUND: Familial Hypercholesterolemia (FH) is the most common monogenic
      disorder that causes premature coronary artery disease (CAD). Our objective was
      to examine the risk of new onset type 2 diabetes mellitus (T2DM) among FH
      patients and unaffected relatives in relation to treatment with different statins
      in the SAFEHEART cohort study. METHODS: This is a cross-sectional and prospective
      cohort study in 2558 FH and 1265 unaffected relatives with a mean follow-up of
      5.9 years. Several pertinent data, such as age, gender, metabolic syndrome, lipid
      profile, body mass index (BMI), waist circumference, HOMA-IR, dose, duration and
      type of statins, were obtained and examined as predictors of incident diabetes.
      RESULTS: The new onset diabetes was 1.7% in FH and 0.2% in non FH patients
      (p=0.001). In multivariate logistic regression, age (OR 1.02, CI 95%: 1.02-1.08),
      HOMA-IR (OR 1.17, CI 95%: 1.03-1.33), metabolic syndrome (OR 3.3, CI 95%: 1.32
      8.28) and specifically plasma glucose, as a component of metabolic syndrome (OR
      15.7, CI 95%: 4.70-52.53) were significant predictors of new onset T2DM in the FH
      group alone. In the adjusted Cox regression model in FH group, age (HR 1.03, CI
      95% 1.00-1.06, p=0.031) and metabolic syndrome (HR 4.16, CI 95% 1.58-10.92,
      p=0.004) remained significant predictors of new onset T2DM. CONCLUSIONS: Our data
      do not support the postulated diabetogenic effect associated with high-dose
      statins use in our cohort of FH patients.

PMID- 26296049
TI  - The incremental value of coronary computerized tomography angiography following
      invasive coronary angiography with an emphasis on equivocal left main stenosis.

PMID- 26296050
TI  - Ranibizumab vs. aflibercept for wet age-related macular degeneration: network
      meta-analysis to understand the value of reduced frequency dosing.
AB  - OBJECTIVE: Although a reduced aflibercept (2.0 mg) injection frequency relative
      to the approved dosing posology is included in national treatment guidelines for
      wet age-related macular degeneration (AMD), there is limited evidence of its
      comparative efficacy. The objective was to compare the efficacy and safety of
      reduced frequency dosing for aflibercept, relative to other approved and marketed
      vascular endothelial growth factor inhibitors for wet AMD, over 12 months.
      RESEARCH DESIGN AND METHODS: Based on a systematic literature review performed
      according to a pre-specified protocol, a Bayesian network meta-analysis (NMA) was
      conducted to indirectly compare posologies of aflibercept and ranibizumab (0.5
      mg). The efficacy outcome, mean change from baseline in best-corrected visual
      acuity (BCVA) on the ETDRS chart, was evaluated at 3 and 12 months; and safety
      data at 12 months. Standard NMA models were used to analyze change at 3 months,
      and fractional polynomial regression over 12 months. Safety data were analyzed
      using binomial models with a logistic link function. RESULTS: Five trials formed
      a complete evidence network. At 3 months, all posologies of aflibercept and
      ranibizumab resulted in similar changes in BCVA. Over 12 months, approved
      posologies of aflibercept and ranibizumab resulted in similar changes from
      baseline, between 6.7 (95% credible interval [CrI], 5.5, 7.8) and 9.1 (8.1, 10.1)
      ETDRS letters; however, reduced frequency aflibercept was associated with a
      smaller change (1.8 letters, [-25.9, 29.2]). There was a trend towards a greater
      change in BCVA, with increasing frequency of dosing. All posologies performed
      similarly with respect to safety, and CrIs were wide. CONCLUSIONS: Approved
      posologies of ranibizumab and aflibercept are similarly effective treatments for
      wet AMD. Reduced frequency aflibercept was associated with the poorest visual
      outcomes, and sample sizes were small. Findings from these analyses provide novel
      evidence of the comparative efficacy and safety of aflibercept and ranibizumab
      for wet AMD.

PMID- 26296051
TI  - ROD-CONE DYSTROPHY ASSOCIATED WITH WILLIAMS SYNDROME.
AB  - PURPOSE: To describe a case of rod-cone dystrophy associated with Williams
      syndrome. METHODS: This is an observational case report. The medical history was
      assessed. Examination included ophthalmoscopy, slit-lamp biomicroscopy, fundus
      autofluorescence imaging, optical coherence tomography, full-field and multifocal
      electroretinography, and fluorescence in situ hybridization for genetic testing.
      RESULTS: A 14-year-old Asian Indian girl with characteristic facies and heart
      murmur, and with findings on ophthalmoscopy, slit-lamp biomicroscopy, fundus
      autofluorescence imaging, optical coherence tomography, full-field
      electroretinography, and multifocal electroretinography consistent with
      panretinal rod-cone dystrophy, has been reported. Fluorescence in situ
      hybridization revealed only 1 copy of the elastin gene on Chromosome 7,
      confirming the diagnosis of Williams syndrome in this patient. CONCLUSION: The
      authors report the first case of a patient with ophthalmic findings
      characteristic for rod-cone dystrophy in the setting of genetically confirmed
      Williams-Beuren syndrome.

PMID- 26296052
TI  - EN FACE OPTICAL COHERENCE TOMOGRAPHY OF MACULAR MICROCYSTS DUE TO OPTIC
      NEUROPATHY FROM NEUROMYELITIS OPTICA.
AB  - PURPOSE: To describe the multimodal imaging, including en face optical coherence
      tomography (OCT) and OCT angiography, findings of a case of macular microcysts
      associated with neuromyelitis optica. METHODS: Findings on clinical examination,
      color fundus photography, fluorescein angiography, fundus autofluorescence,
      visual fields, and OCT including en face OCT and OCT angiography are presented.
      RESULTS: A 12-year-old African American boy presented with bilateral optic
      atrophy from neuromyelitis optica. Clinical examination was notable for bilateral
      optic nerve head pallor. Visual fields of both eyes showed generalized
      depression. Fluorescein angiography and fundus autofluorescence were
      unremarkable. Spectral domain OCT B-scan images showed characteristic
      paracentral, hyporeflective, microcystic lesions in the inner nuclear layer of
      both eyes, and en face OCT images demonstrated a corresponding pattern of large
      paracentral cysts radiating peripherally into smaller diffuse cysts. Optical
      coherence tomographic angiography of the superficial and deep retinal capillary
      plexuses was unremarkable. CONCLUSION: Macular microcysts have been associated
      with various forms of optic atrophy, including neuromyelitis optica. Spectral
      domain and en face OCT imaging of the microcysts demonstrated a very
      characteristic pattern. Normal fluorescein and OCT angiography suggest that
      nonvascular causes, such as Muller cell degeneration, might contribute to the
      etiologic mechanism.

PMID- 26296053
TI  - DOME-SHAPED MACULA WITH THICKENED CHOROID IN AN EMMETROPIC PATIENT.
AB  - PURPOSE: To report a rare case of bilateral dome-shaped macula in an emmetropic
      patient. METHOD: Clinical case report and literature review. RESULTS: A 42-year
      old woman presented with a history of blurred vision in the right eye. Visual
      acuity was 20/30 in the right eye and 20/20 in the left eye. Intraocular pressure
      and anterior segment were unremarkable. Fundus examination revealed dull macular
      reflex and subretinal fluid nasal to the fovea in the right eye and a
      hyperpigmented area inferotemporal to the fovea in the left eye. Spectral domain
      optical coherence tomography showed subretinal fluid under the fovea in the right
      eye and elevation of the macula with increased choroidal thickness in both eyes.
      Fluorescein angiography revealed abnormal hyperfluorescence without any leakage
      in both eyes. B-scan ultrasound showed irregular globe contour with high internal
      reflectivity and dome-shaped lesions at the posterior pole in both eyes. Axial
      length was 24.6 mm in the right eye and 25.6 mm in the left eye. CONCLUSION:
      Although most commonly reported in myopic eyes, dome-shaped macula can occur in
      an emmetropic patient and can be associated with subretinal fluid.

PMID- 26296055
TI  - Formulation Design of Dry Powders for Inhalation.
AB  - Drugs for inhalation are no longer exclusively highly crystalline small
      molecules. They may also be amorphous small molecules, peptides, antibodies, and
      myriad types of engineered proteins. The evolution of respiratory therapeutics
      has created a need for flexible formulation technologies to engineer respirable
      particles. These technologies have enabled medicinal chemists to focus on
      molecular design without concern regarding compatibility of physicochemical
      properties with traditional, blend-based technologies. Therapeutics with diverse
      physicochemical properties can now be formulated as stable and respirable dry
      powders. Particle engineering technologies have also driven the deployment of new
      excipients, giving formulators greater control over particle and powder
      properties. This plays a key role in enabling efficient delivery of drugs to the
      lungs. Engineered powder and device combinations enable aerosols that largely
      bypass the mouth and throat, minimizing the inherent variability among patients
      that arises from differences in oropharyngeal and airway anatomies and in
      breathing profiles. This review explores how advances among molecules, particles,
      and powders have transformed inhaled drug product development. Ultimately, this
      scientific progress will benefit patients, enabling new classes of therapeutics
      to be formulated as dry powder aerosols with improved efficacy, reduced
      variability and side effects, and improved patient adherence.

PMID- 26296054
TI  - IgE receptor signaling in food allergy pathogenesis.
AB  - The pathogenesis of food allergy remains poorly understood. Recent advances in
      the use of murine models have led to discoveries that mast cells and IgE receptor
      signaling not only drive immediate hypersensitivity reactions but also exert an
      immunoregulatory function, promoting the development of allergic sensitivity to
      foods. We review the evidence that IgE, IgE receptors, key signaling kinases and
      mast cells impair oral tolerance to ingested foods, preventing the induction of
      regulatory T cells (Treg) and promoting the acquisition of pro-allergic T helper
      (Th) 2 responses. We discuss innovative strategies that that could be implemented
      to counteract these immunoregulatory effects of IgE-mediated mast cell
      activation, and potentially reverse established sensitization, curing food
      allergy. 

PMID- 26296056
TI  - Identification of novel osteochondrosis--Associated genes.
AB  - During the early stages of articular osteochondrosis, cartilage is retained in
      subchondral bone, but the pathophysiology of this condition of growing humans and
      domestic animals is poorly understood. A subtractive hybridization study was
      undertaken to compare gene expression between the cartilage of early
      experimentally induced equine osteochondrosis lesions and control cartilage. Of
      the many putative differentially expressed genes identified, eight were confirmed
      by quantitative PCR analysis as differentially expressed, in addition to those
      already known to be associated with early lesions. Genes encoding vacuolar H(+)
      ATPase V0 subunit d2 (ATP6V0D2), cathepsin K, integrin-binding sialoprotein,
      integrin alphaV, low density lipoprotein receptor-related protein 4, lumican,
      osteopontin, and thymosin beta4 (TMSB4) were expressed at higher levels in
      lesions than in control cartilage. These genes included 34 genes not previously
      identified in cartilage. Some genes identified as associated with early lesions
      are known chondrocyte hypertrophy-associated genes, and in transmission electron
      microscopy studies normal hypertrophic chondrocytes were observed in lesions.
      Differential expression of ATP6V0D2 and TMSB4 in the cartilage of early naturally
      occurring osteochondrosis lesions was confirmed by immunohistochemistry. These
      results identify novel osteochondrosis-associated genes and provide evidence that
      articular osteochondrosis does not necessarily result from failure of
      chondrocytes to undergo hypertrophy.

PMID- 26296057
TI  - Radon transfer velocity at the water-air interface.
AB  - Radon is a radionuclide that is one of the most commonly used natural tracers,
      for example in groundwater. The transport of radon at the water-air interface is
      investigated in this work at very low turbulence such as when water samples are
      taken for radon measurements. This very important process for the accurate
      measurement of radon in water has, surprisingly, not been investigated very
      often. By using a mathematical model and an experiment the radon transfer
      velocity coefficient (k) from the water-air interface was found to be (1.4+/
      0.2)*10(-6)ms(-1). This radon transfer velocity indicates that the escape is a
      relatively slow process which justifies the use of radon in water measurements. 

PMID- 26296058
TI  - A computational tool for patient specific dosimetry and radiobiological modeling
      of selective internal radiation therapy with (90)Y microspheres.
AB  - In recent years we have witnessed tremendous progress in selective internal
      radiation therapy. In clinical practice, quite often, radionuclide therapy is
      planned using simple models based on standard activity values or activity
      administered per unit body weight or surface area in spite of the admission that
      radiation-dose methods provide more accurate dosimetric results. To address that
      issue, the authors developed a Matlab-based computational software, named Patient
      Specific Yttrium-90 Dosimetry Toolkit (PSYDT). PSYDT was designed for patient
      specific voxel-based dosimetric calculations and radiobiological modeling of
      selective internal radiation therapy with (90)Y microspheres. The developed
      toolkit is composed of three dimensional dose calculations for both
      bremsstrahlung and beta emissions. Subsequently, radiobiological modeling is
      performed on a per-voxel basis and cumulative dose volume histograms (DVHs) are
      generated. In this report we describe the functionality and visualization
      features of PSYDT. 

PMID- 26296059
TI  - A method to evaluate hydraulic fracture using proppant detection.
AB  - Accurate determination of the proppant placement and propped fracture height are
      important for evaluating and optimizing stimulation strategies. A technology
      using non-radioactive proppant and a pulsed neutron gamma energy spectra logging
      tool to determine the placement and height of propped fractures is proposed.
      Gd2O3 was incorporated into ceramic proppant and a Monte Carlo method was
      utilized to build the logging tools and formation models. Characteristic
      responses of the recorded information of different logging tools to fracture
      widths, proppant concentrations and influencing factors were studied. The results
      show that Gd capture gamma rays can be used to evaluate propped fractures and it
      has higher sensitivity to the change of fracture width and traceable proppant
      content compared with the exiting non-radioactive proppant evaluation techniques
      and only an after-fracture measurement is needed for the new method; The changes
      in gas saturation and borehole size have a great impact on determining propped
      fractures when compensated neutron and pulsed neutron capture tool are used. A
      field example is presented to validate the application of the new technique. 

PMID- 26296060
TI  - Preliminary thermoluminescence investigation of commercial pharmaceutical glass
      containers towards the sterilization dosimetry of liquid drugs.
AB  - Drug sterilization with ionizing radiation is a well-established technology,
      which is constantly extending to several products due to its numerous advantages,
      since it allows the heat-free sterilization of heat-sensitive pharmaceutical
      preparations. In a previous study, the possibility to identify irradiated solid
      state drugs by means of OSL and TL was examined with very promising findings. In
      the same respect, the present work aims, for the first time to the authors' best
      knowledge, to explore whether TL can be employed as a method for post
      sterilization dosimetry on commercial liquid-state drugs, by studying the
      properties of their glass containers. Two different types of glass containers
      (bottle and ampoule) of two widely used liquid drugs, i.e., Hexalen(r) and
      Voltaren(r), are used for this purpose. Both glass containers exhibit a linear TL
      dose response for doses up to 6kGy with a stable behavior through time, while no
      significant sensitization of the main peaks is observed. Thus, preliminary
      findings are very promising towards the post-sterilization dosimetry of liquid
      drugs and the use of the containers of commercial liquid drugs for normal and/or
      accidental dosimetry. 

PMID- 26296061
TI  - Patterns of Antibiotic Exposure and Clinical Disease Activity in Inflammatory
      Bowel Disease: A 4-year Prospective Study.
AB  - BACKGROUND: Antimicrobial treatment is known to cause short- and long-term
      changes in the composition of normal human microbiota. The relationship between
      antibiotic use and overall clinical behavior in inflammatory bowel disease (IBD)
      has not been explored. We aim to prospectively characterize patterns of
      antibiotic use and clinical IBD activity in a large IBD cohort. METHODS:
      Prospective observational study from a longitudinal IBD natural history registry
      between 2009 and 2012. Antibiotic prescriptions were identified and categorized
      using electronic medical record data. Cumulative rates over the 4-year study
      period were compared. Demographic, clinical, laboratory, health care utilization,
      and treatment data of the patients with IBD were collected and analyzed. Quality
      of life was measured by Short IBD Questionnaire data. Primary outcomes were
      markers of disease activity including Short IBD Questionnaire scores, C-reactive
      protein levels, health care utilization, and medication use. RESULTS: Seven
      hundred eighteen patients followed over 4 years were included (47.6% male; mean
      age, 46.7 +/- 15.2 yr), 59.9% had Crohn's disease, whereas 38.6% had ulcerative
      colitis. Most patients (66.3%) were exposed to antibiotics during the study
      period. Antibiotic-exposed patients were more likely to have Crohn's disease (63%
      versus 53.7%; P = 0.05), require narcotics (43.7% versus 14.9%; P < 0.0001),
      receive antidepressants (43.1% versus 18.6%; P < 0.001), prednisone (52.7% versus
      31%; P < 0.0001), or biological therapy (52% versus 36.5%; P < 0.0001).
      Antibiotic-exposed patients had a lower mean Short IBD Questionnaire (50.2 +/-
      11.5 versus 56.4 +/- 9.5; P < 0.0001), higher rates of C-reactive protein
      elevation (49.2% versus 31.8%; P < 0.0001), and higher health care utilization
      compared with nonantibiotic-exposed patients. CONCLUSIONS: The majority of
      patients with IBD receive antibiotic treatment, and these individuals demonstrate
      a more severe clinical course.

PMID- 26296062
TI  - Mesalamine, but Not Sulfasalazine, Reduces the Risk of Colorectal Neoplasia in
      Patients with Inflammatory Bowel Disease: An Agent-specific Systematic Review and
      Meta-analysis.
AB  - BACKGROUND: In some studies, 5-aminosalicylates as a class have been associated
      with protective effects against colorectal cancer in inflammatory bowel disease.
      In practice, only mesalamine at doses greater than 1.2 g per day is currently
      widely in this setting. The specific impact of mesalamine at these doses has not
      has not previously been determined. METHODS: We performed a systematic review and
      meta-analysis of the effect of mesalamine on risk of colorectal neoplasia (CRN)
      from prior cohort and case-control studies. Sensitivity analyses for study
      setting and case definition were performed. A quality assessment was made of all
      included studies. RESULTS: Mesalamine was associated with a modest reduction in
      the odds ratio (OR) of CRN (OR = 0.6, 95% confidence interval, 0.4-0.9, P =
      0.04). This effect was only noted in hospital-based studies and only in the
      reduction of all CRN (not cancers alone). Patients prescribed doses >1.2 g per
      day had a lower risk of CRN (OR = 0.5, 95% confidence interval, 0.3-0.9, P =
      0.02) than lower doses. This effect was also only present in the hospital-based
      studies. In contrast, there was no reduction in the risk of CRN in patients
      prescribed sulfasalazine (OR = 0.8, 95% confidence interval, 0.5-1.2, P = 0.3),
      regardless of study setting. CONCLUSIONS: Mesalamine, particularly at doses >1.2
      g per day, produces a modest reduction in the risk of CRN in inflammatory bowel
      disease patient populations from referral centers. Sulfasalazine does not seem to
      reduce the risk. No benefit was noted in population-based studies.

PMID- 26296063
TI  - Protective Role of beta-arrestin2 in Colitis Through Modulation of T-cell
      Activation.
AB  - beta-arrestin2 (beta-arr2), identified as a scaffolding protein in G-protein
      coupled receptor desensitization, is a negative regulator of inflammation in
      polymicrobial sepsis. In this study, we wanted to investigate the role of beta
      arr2 in intestinal inflammation, a site of persistent microbial stimulation. In
      the absence of beta-arr2, mice exhibited greater extent of mucosal inflammation
      determined by cellular infiltration and expression of inflammatory mediators even
      under homeostatic conditions. Furthermore, beta-arr2-deficient mice were more
      susceptible to dextran sulfate sodium-induced colitis as demonstrated by greater
      body weight loss, higher disease activity index, and shortened colon as compared
      with wild-type mice. We also show that T cells from beta-arr2 knockout mice
      exhibit altered activation status under both basal and colitic conditions,
      implicating their involvement in disease induction. Further assessment of the
      role of beta-arr2 in intrinsic T-cell differentiation confirmed its importance in
      T-cell polarization. Using the T-cell transfer model of colitis, we demonstrate
      that T-cell-specific beta-arr2 is important in limiting colitic inflammation;
      however, it plays a paradoxical role in concurrent systemic wasting disease.
      Together, our study highlights a critical negative regulatory role of beta-arr2
      in intestinal inflammation and demonstrates a distinct role of T-cell-specific
      beta-arr2 in systemic wasting disease. 

PMID- 26296064
TI  - Prevalence and Risk Factors for Functional Vitamin B12 Deficiency in Patients
      with Crohn's Disease.
AB  - BACKGROUND: Crohn's disease (CD) is a risk factor for vitamin B12 deficiency due
      to frequent involvement of the terminal ileum. Conventional screening for B12
      deficiency with serum B12 is relatively insensitive and measures total B12
      concentration, of which a minority is present in a biologically active form.
      Holotranscobalamin (holoTC) combined with methylmalonic acid (MMA) is believed to
      be more accurate in identifying impaired B12 status. We evaluated the prevalence
      and risk factors for B12 deficiency using holoTC supported by MMA among patients
      with CD. METHODS: We performed a single-center service evaluation of 381 patients
      with CD who underwent B12 assessment (holoTC/MMA) and compared them with 141
      patients with ulcerative colitis. Eighty-nine patients with CD underwent paired
      serum B12 and holoTC. Among patients with CD, risk factors including terminal
      ileal resection length, ileal inflammation on endoscopy, and disease
      characteristics on magnetic resonance imaging were recorded. RESULTS: Prevalence
      of B12 deficiency among patients with CD was 33% compared with 16% in ulcerative
      colitis (P < 0.0001). In 89 patients who underwent paired tests, conventional
      testing identified B12 deficiency in 5% of patients with CD, which increased to
      32% using holoTC/MMA. Independent risk factors for B12 deficiency were ileal
      resection length <=20 cm (odds ratio: 3.0, 95% confidence interval, 1.5-6.0, P =
      0.002) and >20 cm (odds ratio: 6.7, 95% confidence interval, 3.0-14.7, P <
      0.0001) and ileal inflammation (odds ratio: 3.9, 95% confidence interval, 2.2
      6.9, P < 0.0001). On magnetic resonance imaging, active terminal ileal
      inflammation (P = 0.02) and an increased disease burden (>=1 skip lesion, P =
      0.01 and prestenotic dilatation >3 cm, P = 0.01) were associated with B12
      deficiency. CONCLUSIONS: Vitamin B12 deficiency is common in patients with CD.
      holoTC supported by MMA identifies patients with B12 deficiency considered
      replete on conventional testing.

PMID- 26296065
TI  - Experimental insights into the importance of aquatic bacterial community
      composition to the degradation of dissolved organic matter.
AB  - Bacteria play a central role in the cycling of carbon, yet our understanding of
      the relationship between the taxonomic composition and the degradation of
      dissolved organic matter (DOM) is still poor. In this experimental study, we were
      able to demonstrate a direct link between community composition and ecosystem
      functioning in that differently structured aquatic bacterial communities differed
      in their degradation of terrestrially derived DOM. Although the same amount of
      carbon was processed, both the temporal pattern of degradation and the compounds
      degraded differed among communities. We, moreover, uncovered that low-molecular
      weight carbon was available to all communities for utilisation, whereas the
      ability to degrade carbon of greater molecular weight was a trait less widely
      distributed. Finally, whereas the degradation of either low- or high-molecular
      weight carbon was not restricted to a single phylogenetic clade, our results
      illustrate that bacterial taxa of similar phylogenetic classification differed
      substantially in their association with the degradation of DOM compounds.
      Applying techniques that capture the diversity and complexity of both bacterial
      communities and DOM, our study provides new insight into how the structure of
      bacterial communities may affect processes of biogeochemical significance. 

PMID- 26296066
TI  - Contribution of neutral processes to the assembly of gut microbial communities in
      the zebrafish over host development.
AB  - Despite their importance to host health and development, the communities of
      microorganisms associated with humans and other animals are characterized by a
      large degree of unexplained variation across individual hosts. The processes that
      drive such inter-individual variation are not well understood. To address this,
      we surveyed the microbial communities associated with the intestine of the
      zebrafish, Danio rerio, over developmental time. We compared our observations of
      community composition and distribution across hosts with that predicted by a
      neutral assembly model, which assumes that community assembly is driven solely by
      chance and dispersal. We found that as hosts develop from larvae to adults, the
      fit of the model to observed microbial distributions decreases, suggesting that
      the relative importance of non-neutral processes, such as microbe-microbe
      interactions, active dispersal, or selection by the host, increases as hosts
      mature. We also observed that taxa which depart in their distributions from the
      neutral prediction form ecologically distinct sub-groups, which are
      phylogenetically clustered with respect to the full metacommunity. These results
      demonstrate that neutral processes are sufficient to generate substantial
      variation in microbiota composition across individual hosts, and suggest that
      potentially unique or important taxa may be identified by their divergence from
      neutral distributions. 

PMID- 26296067
TI  - Seasonal time bombs: dominant temperate viruses affect Southern Ocean microbial
      dynamics.
AB  - Rapid warming in the highly productive western Antarctic Peninsula (WAP) region
      of the Southern Ocean has affected multiple trophic levels, yet viral influences
      on microbial processes and ecosystem function remain understudied in the Southern
      Ocean. Here we use cultivation-independent quantitative ecological and
      metagenomic assays, combined with new comparative bioinformatic techniques, to
      investigate double-stranded DNA viruses during the WAP spring-summer transition.
      This study demonstrates that (i) temperate viruses dominate this region,
      switching from lysogeny to lytic replication as bacterial production increases,
      and (ii) Southern Ocean viral assemblages are genetically distinct from lower
      latitude assemblages, primarily driven by this temperate viral dominance. This
      new information suggests fundamentally different virus-host interactions in polar
      environments, where intense seasonal changes in bacterial production select for
      temperate viruses because of increased fitness imparted by the ability to switch
      replication strategies in response to resource availability. Further, temperate
      viral dominance may provide mechanisms (for example, bacterial mortality
      resulting from prophage induction) that help explain observed temporal delays
      between, and lower ratios of, bacterial and primary production in polar versus
      lower-latitude marine ecosystems. Together these results suggest that temperate
      virus-host interactions are critical to predicting changes in microbial dynamics
      brought on by warming in polar marine systems. 

PMID- 26296068
TI  - Multivariable Analysis of the Association Between Antimicrobial Use and
      Antimicrobial Resistance in Escherichia coli Isolated from Apparently Healthy
      Pigs in Japan.
AB  - The objective of this study was to investigate the association between
      antimicrobial agent use and antimicrobial resistance in Escherichia coli isolated
      from healthy pigs using data from 2004 to 2007 in the Japanese Veterinary
      Antimicrobial Resistance Monitoring System (JVARM). Fecal E. coli isolates from
      250 pigs (one isolate each from a pig per farm) were examined for antimicrobial
      resistance. Information on the use of antimicrobials within preceding 6 months
      and types of farms recorded in JVARM was collected and statistically analyzed
      against the resistance patterns. In the univariate analysis, associations between
      both therapeutic and feed additive use of antimicrobials, and resistance to
      dihydrostreptomycin, gentamicin, kanamycin, ampicillin, cefazolin, ceftiofur,
      oxytetracycline, chloramphenicol, trimethoprim, nalidixic acid, enrofloxacin,
      colistin, and bicozamycin, and husbandry factors were investigated. In
      multivariable analysis, generalized estimating equations were used to control
      geographical intraclass correlation. Confounding for structurally unrelated
      associations was tested using generalized linear models. The results suggested
      direct and cross selections in the associations between use of aminoglycosides in
      reproduction farms and resistance to kanamycin, use of tetracyclines in larger
      farms and resistance to oxytetracycline, use of beta-lactams and resistance to
      ampicillin, use of phenicols and resistance to chloramphenicol, and use of
      fluoroquinolones and resistance to nalidixic acid and enrofloxacin. Coselection
      was suggested in the use of tetracyclines and chloramphenicol resistance. The
      associations between use of beta-lactams and dihydrostreptomycin resistance, use
      of macrolides and ampicillin and oxytetracycline resistance, and use of colistin
      and kanamycin resistance were significant, but were confounded by the
      simultaneous use of homologous antimicrobials. 

PMID- 26296070
TI  - Overuse or underuse? An observation of pesticide use in China.
AB  - Pesticide use has experienced a dramatic increase worldwide, especially in China,
      where a wide variety of pesticides are used in large amounts by farmers to
      control crop pests. While Chinese farmers are often criticized for pesticide
      overuse, this study shows the coexistence of overuse and underuse of pesticide
      based on the survey data of pesticide use in rice, cotton, maize, and wheat
      production in three provinces in China. A novel index amount approach is proposed
      to convert the amount of multiple pesticides used to control the same pest into
      an index amount of a referenced pesticide. We compare the summed index amount
      with the recommended dosage range of the referenced pesticide to classify whether
      pesticides are overused or underused. Using this new approach, the following main
      results were obtained. Pesticide overuse and underuse coexist after examining a
      total of 107 pesticides used to control up to 54 crop pests in rice, cotton,
      maize, and wheat production. In particular, pesticide overuse in more than half
      of the total cases for 9 crop pest species is detected. In contrast, pesticide
      underuse accounts for more than 20% of the total cases for 11 pests. We further
      indicate that the lack of knowledge and information on pesticide use and pest
      control among Chinese farmers may cause the coexistence of pesticide overuse and
      underuse. Our analysis provides indirect evidence that the commercialized
      agricultural extension system in China probably contributes to the coexistence of
      overuse and underuse. To improve pesticide use, it is urgent to reestablish the
      monitoring and forecasting system regarding pest control in China. 

PMID- 26296069
TI  - Physiologically based pharmacokinetics model predicts the lack of inhibition by
      repaglinide on the metabolism of pioglitazone.
AB  - PURPOSE: Repaglinide and pioglitazone are both CYP2C8 and CYP3A4 substrates. This
      study was to determine whether repaglinide has an inhibitory effect on the
      metabolism of pioglitazone in vitro, in silico and in vivo. METHOD: In vitro, the
      effect of repaglinide on the metabolism of pioglitazone was assessed in pooled
      human liver microsomes. In silico, an IVIVE-PBPK linked model was built with
      Simcyp(r). Then, a randomized, 2-phase cross-over clinical study was conducted in
      12 healthy volunteers. RESULTS: Repaglinide showed a strong inhibitory effect on
      the metabolism of pioglitazone in vitro (Ki  = 0.0757 um), [I]/Ki  > 0.1. The
      Simcyp(r) prediction ratios of AUC and Cmax between the two treatment groups were
      both about 1.01. The pharmacokinetics of pioglitazone in clinical trials showed
      no significant difference between these two treatment groups (p > 0.05).
      CONCLUSION: Repaglinide has no significant inhibitory effect on the metabolism of
      pioglitazone in vivo, which is inconsistent with the in vitro results. The lack
      of an inhibitory effect was partly due to extensive plasma protein binding and to
      the high in vivo clearance of repaglinide, for the concentration of repaglinide
      in vivo was far smaller than in vitro.

PMID- 26296071
TI  - Changes in the persistence of two phenylurea herbicides in two Mediterranean
      soils under irrigation with low- and high-quality water: A laboratory approach.
AB  - The disappearance of two phenylurea herbicides, chlorotoluron (CHL) and
      isoproturon (IPU), in two Mediterranean soils, an agricultural calcareous soil
      (S5) and an organic forest soil (S2), was assessed under irrigation with high-
      and low-quality water. Irrigation with wastewater, as opposed to irrigation with
      high-quality water, increased the degradation rate of both herbicides in both
      soils. For each soil, the decay rate of IPU was always higher than that of CHL,
      and both pesticides disappeared more rapidly from S5 with lower clay and organic
      carbon content than from S2. The degradation rate was inversely related with
      pesticide sorption on soil, because increased sorption would reduce pesticide
      bioavailability for decomposition. In most cases the residual concentration in
      soil of both phenylurea herbicides was better fitted to a bi-exponential decay
      model than to first-order or first-order with plateau models. Dehydrogenase
      activity, used as an indication of microbial activity, was very high in S2 in
      comparison with S5, but was not related to pesticide disappearance. 

PMID- 26296073
TI  - Decomplexation and subsequent reductive removal of EDTA-chelated Cu II by zero
      valent iron coupled with a weak magnetic field: Performances and mechanisms.
AB  - The feasibility of EDTA-chelated Cu(II) (Cu(II)-EDTA) removal by zero-valent iron
      (Fe(0)) in the presence of a weak magnetic field (WMF) and the involved
      mechanisms were systematically investigated. Fe(0) combined with WMF (Fe(0)/WMF)
      was very effective for removing Cu(II)-EDTA at pH 4.0-6.0 with the rate constants
      ranging from 0.1190 min(-1) to 0.0704 min(-1). Little passivation of Fe(0) was
      observed during Cu(II)-EDTA removal by Fe(0)/WMF in 8 consecutive runs when 10.0
      mg L(-1) Cu(II)-EDTA was dosed before the initiation of each run. The evidences
      presented in this study verified that Cu(II)-EDTA was removed by decomplexation
      followed by reduction/adsorption. In brief, Fe(II) released from Fe(0) corrosion
      was rapidly oxidized by oxygen to Fe(III) to chelate with EDTA and release free
      Cu(II), and the detached Cu(II) ions were subsequently reduced/removed by
      Fe(0)/Fe(II) and co-precipitated by the generated iron (hydr)-oxides. To advance
      the application of Fe(0)/WMF technology in real practice, a magnetic propeller
      agitator was designed to offer WMF inside the reactor, which could greatly
      improve Cu(II)-EDTA removal by Fe(0) and be easily amplified.

PMID- 26296074
TI  - Capture of formaldehyde by adsorption on nanoporous materials.
AB  - The aim of this work is to assess the capability of a series of nanoporous
      materials to capture gaseous formaldehyde by adsorption in order to develop air
      treatment process and gas detection in workspaces or housings. Adsorption
      desorption isotherms have been accurately measured at room temperature by TGA
      under very low pressure (p<2 hPa) on various adsorbents, such as zeolites,
      mesoporous silica (SBA15), activated carbon (AC NORIT RB3) and metal organic
      framework (MOF, Ga-MIL-53), exhibiting a wide range of pore sizes and surface
      properties. Results reveal that the NaX, NaY and CuX faujasite (FAU) zeolites are
      materials which show strong adsorption capacity and high affinity toward
      formaldehyde. In addition, these materials can be completely regenerated by
      heating at 200 degrees C under vacuum. These cationic zeolites are therefore
      promising candidates as adsorbents for the design of air depollution process or
      gas sensing applications.

PMID- 26296072
TI  - Calcium and ROS: A mutual interplay.
AB  - Calcium is an important second messenger involved in intra- and extracellular
      signaling cascades and plays an essential role in cell life and death decisions.
      The Ca(2+) signaling network works in many different ways to regulate cellular
      processes that function over a wide dynamic range due to the action of buffers,
      pumps and exchangers on the plasma membrane as well as in internal stores.
      Calcium signaling pathways interact with other cellular signaling systems such as
      reactive oxygen species (ROS). Although initially considered to be potentially
      detrimental byproducts of aerobic metabolism, it is now clear that ROS generated
      in sub-toxic levels by different intracellular systems act as signaling molecules
      involved in various cellular processes including growth and cell death.
      Increasing evidence suggests a mutual interplay between calcium and ROS signaling
      systems which seems to have important implications for fine tuning cellular
      signaling networks. However, dysfunction in either of the systems might affect
      the other system thus potentiating harmful effects which might contribute to the
      pathogenesis of various disorders. 

PMID- 26296075
TI  - Decreased spermatogenesis led to alterations of testis-specific gene expression
      in male mice following nano-TiO2 exposure.
AB  - Although TiO2 nanoparticles (NPs) exposure has been demonstrated to cross blood
      testis barrier and accumulate in the testis resulting in the reduction of sperm
      numbers, limited data with respect to the molecular mechanism of decreased
      spermatogenesis caused by TiO2 NP exposure. In this research, testicular damage,
      sperm number and alterations in testis-specific gene expressions in male mice
      induced by intragastric administration with TiO2 NPs for six months were
      investigated. It was found out that TiO2 NPs could migrate to cells, deposit in
      the testis and epididymis and thus cause damages to relevant organs, which are,
      to be more specific, the reductions of total sperm concentrations and sperm
      motility and an enhancement in the number of abnormal sperms in the cauda
      epididymis. Furthermore, the individual expression regarding to the mRNAs and
      proteins of testis-specific genes, including Cdc2, Cyclin B1, Dmcl, TERT, Tesmin,
      TESP-1, XPD and XRCCI, were significantly declined, whereas Gsk3-beta and PGAM4
      expressions were greatly elevated in mouse testis due to the exposures, which in
      fact implied that the reduced spermatogenesis may be involved in the alternated
      testis-specific gene expressions in those exposed male mice. 

PMID- 26296076
TI  - Association between phthalate metabolites and biomarkers of reproductive function
      in 1066 Chinese men of reproductive age.
AB  - Phthalates are suspected endocrine disrupting chemicals that impair male
      reproductive function in animal and epidemiological studies. We investigated
      associations between urinary phthalate metabolites and acrosin activity, along
      with that between insulin like-factor 3 (INSL3), a Leydig cell function marker,
      in Chinese adult men and assessed the association between the metabolites and
      male reproductive function. Serum levels of INSL3 and other hormones, semen
      parameters, and urinary concentrations of 14 phthalate metabolites in 1066 men
      were measured. The unadjusted concentrations of phthalates were included as
      independent variables and urinary creatinine as a separate covariate. INSL3 was
      negatively associated with mono-2-ethylhexyl phthalate (MEHP) and %MEHP
      [percentage of MEHP to all di(2-ethylhexyl) phthalate (DEHP) metabolites].
      Acrosin activity was negatively associated with mono-n-butyl phthalate (MBP),
      mono-isobutyl phthalate (MiBP), MEHP and %MEHP. MBP and MiBP were also negatively
      associated with total testosterone (T), free androgen index (FAI), free
      testosterone (FT), luteinizing hormone (LH) and sperm morphology and positively
      associated with DNA fragmentation index (DFI). A negative association between
      %MEHP and sperm motility was observed. Several other metabolites were also
      associated with reproductive function. This is the first report on the inverse
      associations of phthalate metabolites with acrosin activity and INSL3. Phthalates
      may cause multiple adverse results on reproductive function at environmental
      levels. 

PMID- 26296078
TI  - Self-injurious, aggressive and destructive behaviour in children with severe
      intellectual disability: Prevalence, service need and service receipt in the UK.
AB  - Children with severe intellectual disabilities are at increased risk of
      presenting with self-injurious, aggressive and destructive behaviour. Severity of
      these behaviours is an important predictor of psychological and behavioural
      service use by people with intellectual disabilities. However, studies suggest
      that the needs of children with intellectual disabilities and their families are
      not being met. The aims of the present study were to: (1) describe the self
      injurious, aggressive and destructive behaviours and subsequent support needs of
      children with severe intellectual disabilities attending special schools in one
      major city within the UK, (2) compare teacher and primary carer ratings of
      behaviour and service need and (3) explore the extent to which the needs of
      children with intellectual disabilities are being met in terms of contact with
      relevant specialist services. Questionnaires were completed by teachers and
      primary family carers of children with a severe intellectual disability. Results
      indicated that at least 5.3% and 4.1% of children showed at least one behaviour
      at a clinically significant frequency and management difficulty respectively.
      Primary carers identified more children with significant behaviour difficulties
      and support needs than teachers. The odds for children presenting with high
      levels of the behaviours of interest for having a service need for behavioural
      intervention were at least 13 times those for children not showing the
      behaviours, yet only doubled for contact with a specialist relevant health-care
      professional. These results quantify the magnitude of the substantial gap between
      level of need and relevant support received. 

PMID- 26296079
TI  - The clinimetric properties of aerobic and anaerobic fitness measures in adults
      with cerebral palsy: A systematic review of the literature.
AB  - OBJECTIVE: To analyze the clinimetric properties of maximal aerobic and anaerobic
      fitness measurement protocols in adults with cerebral palsy (CP). DATA SOURCES: A
      systematic search through March 2015 of databases PubMed, Embase, SPORTDiscus and
      PsycINFO was performed with medical subject heading terms for 'cerebral palsy'
      combined with search terms adults or adolescents and multiple text words for
      fitness and exercise tests that yielded 864 articles. STUDY SELECTION: Abstracts
      were screened by two reviewers to identify use of maximal fitness measurements in
      adolescents (14-18yrs) or adults (>18yrs) with CP of all abilities. Ninety-four
      articles were reviewed. No studies of adolescent (14-18yrs) qualified. Eight
      articles reported clinimetric properties for adults with CP who walk or propel a
      wheelchair independently. Five articles reported on aerobic capacity, one
      reported on anaerobic capacity and two reported on both. DATA EXTRACTION:
      Methodological quality of the studies was rated using portions of the COSMIN
      (COnsensus-based Standards for the selection of health status Measurement
      INstruments) checklist. Quality of the measurement protocols was evaluated based
      on statistical strength of the clinimetrics. Synthesis of the overall evidence
      was based on the Cochrane review group guidelines which combine methodological
      quality and statistical strength. DATA SYNTHESIS: Eight articles reported on 4
      aerobic and 1 anaerobic protocols. Overall synthesis revealed that for ambulatory
      adults with CP there is (i) moderate evidence for good reliability and good
      construct validity of maximal aerobic and anaerobic cycle tests, (ii) moderate
      evidence for good criterion validity of sub-maximal aerobic cycle tests, and
      (iii) strong evidence for poor criterion validity of the six-minute walk test as
      a maximal aerobic test. And for adults who propel a wheelchair there is limited
      evidence of good reliability for maximal aerobic wheelchair ergometer tests.
      CONCLUSIONS: Limited quality research exists on the clinimetric properties of
      aerobic and anaerobic capacity measures for adults with CP who have independent
      mobility. Quality aerobic and anaerobic measures for adults with more severe
      mobility impairments are absent.

PMID- 26296077
TI  - GBA Variants are associated with a distinct pattern of cognitive deficits in
      Parkinson's disease.
AB  - BACKGROUND: Loss-of-function mutations in the GBA gene are associated with more
      severe cognitive impairment in PD, but the nature of these deficits is not well
      understood and whether common GBA polymorphisms influence cognitive performance
      in PD is not yet known. METHODS: We screened the GBA coding region for mutations
      and the E326K polymorphism in 1,369 PD patients enrolled at eight sites from the
      PD Cognitive Genetics Consortium. Participants underwent assessments of learning
      and memory (Hopkins Verbal Learning Test-Revised), working memory/executive
      function (Letter-Number Sequencing Test and Trail Making Test A and B), language
      processing (semantic and phonemic verbal fluency), visuospatial abilities (Benton
      Judgment of Line Orientation), and global cognitive function (MoCA). We used
      linear regression to test for association between genotype and cognitive
      performance with adjustment for important covariates and accounted for multiple
      testing using Bonferroni's corrections. RESULTS: Mutation carriers (n = 60; 4.4%)
      and E326K carriers (n = 65; 4.7%) had a higher prevalence of dementia (mutations,
      odds ratio = 5.1; P = 9.7 * 10(-6) ; E326K, odds ratio = 6.4; P = 5.7 * 10(-7) )
      and lower performance on Letter-Number Sequencing (mutations, corrected P[Pc ] =
      9.0 * 10(-4) ; E326K, Pc  = 0.036), Trail Making B-A (mutations, Pc  = 0.018;
      E326K, Pc  = 0.018), and Benton Judgment of Line Orientation (mutations, Pc  =
      0.0045; E326K, Pc  = 0.0013). CONCLUSIONS: Both GBA mutations and E326K are
      associated with a distinct cognitive profile characterized by greater impairment
      in working memory/executive function and visuospatial abilities in PD patients.
      The discovery that E326K negatively impacts cognitive performance approximately
      doubles the proportion of PD patients we now recognize are at risk for more
      severe GBA-related cognitive deficits.

PMID- 26296080
TI  - A screening on Specific Learning Disorders in an Italian speaking high genetic
      homogeneity area.
AB  - The aim of the present research is to investigate the prevalence of Specific
      Learning Disorders (SLD) in Ogliastra, an area of the island of Sardinia, Italy.
      Having experienced centuries of isolation, Ogliastra has become a high genetic
      homogeneity area, and is considered particularly interesting for studies on
      different kinds of pathologies. Here we are going to describe the results of a
      screening carried out throughout 2 consecutive years in 49 second grade classes
      (24 considered in the first year and 25 in the second year of the study) of the
      Ogliastra region. A total of 610 pupils (average age 7.54 years; 293 female, 317
      male) corresponding to 68.69% of all pupils who were attending second grade in
      the area, took part in the study. The tool used for the screening was "RSR-DSA.
      Questionnaire for the detection of learning difficulties and disorders", which
      allowed the identification of 83 subjects at risk (13.61% of the whole sample
      involved in the study). These subjects took part in an enhancement training
      program of about 6 months. After the program, pupils underwent assessment for
      reading, writing and calculation abilities, as well as cognitive assessment.
      According to the results of the assessment, the prevalence of SLDs is 6.06%. For
      what concerns dyslexia, 4.75% of the total sample manifested this disorder either
      in isolation or in comorbidity with other disorders. According to the first
      national epidemiological investigation carried out in Italy, the prevalence of
      dyslexia is 3.1-3.2%, which is lower than the prevalence obtained in the present
      study. Given the genetic basis of SLDs, this result, together with the presence
      of several cases of SLD in isolation (17.14%) and with a 3:1 ratio of males to
      females diagnosed with a SLD, was to be expected in a sample coming from a high
      genetic homogeneity area. 

PMID- 26296082
TI  - Improved sensitivity by use of gas chromatography-positive chemical ionization
      triple quadrupole mass spectrometry for the analysis of drug related substances.
AB  - In 2013, the World Anti-Doping Agency (WADA) drastically lowered the minimum
      required performance levels (MRPLs) of most doping substances, demanding a
      substantial increase in sensitivity of the existing methods. For a number of
      compounds, conventional electron impact ionization gas chromatography tandem mass
      spectrometry (GC-EI-MS/MS) is often no longer sufficient to reach these MRPLs and
      new strategies are required. In this study, the capabilities of positive ion
      chemical ionization (PICI) GC-MS/MS are investigated for a wide range of drug
      related compounds of various classes by injection of silylated reference
      standards. Ammonia as PICI reagent gas had superior characteristics for GC-MS/MS
      purposes than methane. Compared to GC-EI-MS/MS, PICI (with ammonia as reagent
      gas) provided more selective ion transitions and consequently, increased
      sensitivity by an average factor of 50. The maximum increase (by factor of 500
      1000) was observed in the analysis of stimulants, namely chlorprenaline,
      furfenorex and phentermine. In total, improved sensitivity was obtained for 113
      out of 120 compounds. A new GC-PICI-MS/MS method has been developed and evaluated
      for the detection of a wide variety of exogenous doping substances and the
      quantification of endogenous steroids in urine in compliance with the required
      MRPLs established by WADA in 2013. The method consists of a hydrolysis and
      extraction step, followed by derivatization and subsequent 1MUL pulsed splitless
      injection on GC-PICI-MS/MS (16min run). The increased sensitivity allows the set
      up of a balanced screening method that meets the requirements for both
      quantitative and qualitative compounds: sufficient capacity and resolution in
      combination with high sensitivity and short analysis time. This resulted in
      calibration curves with a wide linear range (e.g., 48-9600ng/mL for androsterone
      and etiochanolone; all r(2)>0.99) without compromising the requirements for the
      qualitative compounds. 

PMID- 26296081
TI  - Enrichment Analysis Identifies Functional MicroRNA-Disease Associations in
      Humans.
AB  - Substantial evidence has shown that microRNAs (miRNAs) may be causally linked to
      the occurrence and progression of human diseases. Herein, we conducted an
      enrichment analysis to identify potential functional miRNA-disease associations
      (MDAs) in humans by integrating currently known biological data: miRNA-target
      interactions (MTIs), protein-protein interactions, and gene-disease associations.
      Two contributing factors to functional miRNA-disease associations were
      quantitatively considered: the direct effects of miRNA that target disease
      related genes, and indirect effects triggered by protein-protein interactions.
      Ninety-nine miRNAs were scanned for possible functional association with 2223
      MeSH-defined human diseases. Each miRNA was experimentally validated to target >=
      10 mRNA genes. Putative MDAs were identified when at least one MTI was
      confidently validated for a disease. Overall, 19648 putative MDAs were found, of
      which 10.0% was experimentally validated. Further results suggest that filtering
      for miRNAs that target a greater number of disease-related genes (n >= 8) can
      significantly enrich for true MDAs from the set of putative associations
      (enrichment rate = 60.7%, adjusted hypergeometric p = 2.41*10-91). Considering
      the indirect effects of miRNAs further elevated the enrichment rate to 72.6%. By
      using this method, a novel MDA between miR-24 and ovarian cancer was found.
      Compared with scramble miRNA overexpression of miR-24 was validated to remarkably
      induce ovarian cancer cells apoptosis. Our study provides novel insight into
      factors contributing to functional MDAs by integrating large quantities of
      previously generated biological data, and establishes a feasible method to
      identify plausible associations with high confidence. 

PMID- 26296083
TI  - A Refined Neuronal Population Measure of Visual Attention.
AB  - Neurophysiological studies of cognitive mechanisms such as visual attention
      typically ignore trial-by-trial variability and instead report mean differences
      averaged across many trials. Advances in electrophysiology allow for the
      simultaneous recording of small populations of neurons, which may obviate the
      need for averaging activity over trials. We recently introduced a method called
      the attention axis that uses multi-electrode recordings to provide estimates of
      attentional state of behaving monkeys on individual trials. Here, we refine this
      method to eliminate problems that can cause bias in estimates of attentional
      state in certain scenarios. We demonstrate the sources of these problems using
      simulations and propose an amendment to the previous formulation that provides
      superior performance in trial-by-trial assessments of attentional state. 

PMID- 26296084
TI  - Casitas B-Lineage Lymphoma RING Domain Inhibitors Protect Mice against High-Fat
      Diet-Induced Obesity and Insulin Resistance.
AB  - The casitas b-lineage lymphoma (c-Cbl) is an important adaptor protein with an
      intrinsic E3 ubiquitin ligase activity that interacts with E2 proteins such as
      UbCH7. c-Cbl plays a vital role in regulating receptor tyrosine kinase signaling.
      c-Cbl involves in whole-body energy homeostasis, which makes it a potential
      target for the treatment of type 2 diabetes and obesity. In the present study, we
      have designed two parental peptides and 55 modified peptides based on the
      structure of UbCH7 loop L1 and L2. Thirteen of the modified peptides showed
      increased inhibitory activity in a fluorescence polarization-based assay. In the
      in vivo proof of study principle, mice treated with peptides 10, 34, 49 and 51
      were protected against high-fat diet-induced obesity and insulin resistant. These
      inhibitors may potentially lead to new therapeutic alternatives for obesity and
      type 2 diabetes. 

PMID- 26296085
TI  - Cucurbitacin I Attenuates Cardiomyocyte Hypertrophy via Inhibition of Connective
      Tissue Growth Factor (CCN2) and TGF- beta/Smads Signalings.
AB  - Cucurbitacin I is a naturally occurring triterpenoid derived from Cucurbitaceae
      family plants that exhibits a number of potentially useful pharmacological and
      biological activities. However, the therapeutic impact of cucurbitacin I on the
      heart has not heretofore been reported. To evaluate the functional role of
      cucurbitacin I in an in vitro model of cardiac hypertrophy, phenylephrine (PE)
      stimulated cardiomyocytes were treated with a sub-cytotoxic concentration of the
      compound, and the effects on cell size and mRNA expression levels of ANF and beta
      MHC were investigated. Consequently, PE-induced cell enlargement and upregulation
      of ANF and beta-MHC were significantly suppressed by pretreatment of the
      cardiomyocytes with cucurbitacin I. Notably, cucurbitacin I also impaired
      connective tissue growth factor (CTGF) and MAPK signaling, pro-hypertrophic
      factors, as well as TGF-beta/Smad signaling, the important contributing factors
      to fibrosis. The protective impact of cucurbitacin I was significantly blunted in
      CTGF-silenced or TGF-beta1-silenced hypertrophic cardiomyocytes, indicating that
      the compound exerts its beneficial actions through CTGF. Taken together, these
      findings signify that cucurbitacin I protects the heart against cardiac
      hypertrophy via inhibition of CTGF/MAPK, and TGF- beta/Smad-facilitated events.
      Accordingly, the present study provides new insights into the defensive capacity
      of cucurbitacin I against cardiac hypertrophy, and further suggesting
      cucurbitacin I's utility as a novel therapeutic agent for the management of heart
      diseases. 

PMID- 26296086
TI  - Uninterpretable Dynamic Susceptibility Contrast-Enhanced Perfusion MR Images in
      Patients with Post-Treatment Glioblastomas: Cross-Validation of Alternative
      Imaging Options.
AB  - PURPOSE: The purpose of this study was to evaluate the accuracy of diffusion
      weighted imaging (DWI) and dynamic contrast-enhanced (DCE) perfusion MR imaging
      for distinguishing tumor recurrence from post-treatment effect as alternatives to
      dynamic-susceptibility contrast-enhanced (DSC) perfusion MR imaging when the DSC
      image is uninterpretable. MATERIALS AND METHODS: This retrospective study was
      approved by our institutional review board. Seventy one post-treatment
      glioblastoma patients who showed enlarged contrast-enhancing lesions on follow-up
      MR images after concurrent chemoradiotherapy and uninterpretable DSC images for
      corresponding enhancing lesions, underwent additional DWI and DCE MR imaging. The
      primary outcome was the frequency of interpretable DWI and DCE MR cases in these
      71 patients. The secondary outcome was the area under the receiver operating
      characteristic curve (AUC) of DWI and DCE imaging parameters for distinguishing
      tumor recurrence from post-treatment effect in selected patients with
      interpretable DWI and DCE images. The imaging parameters were quantified as 10%
      cumulative histogram cutoff of apparent diffusion coefficient (ADC10) and 90%
      cumulative histogram cutoff of initial area under the time signal intensity curve
      (IAUC90). The AUCs were cross-validated by using leave-one-out method. RESULTS:
      Of the 71 patients, the uninterpretable DSC images were associated with treatment
      related hemorrhage within the corresponding enhancing lesions (n = 54, 76.1%) and
      a near skull base location (n = 17, 23.9%). The frequencies of interpretable DWI
      and DCE image were 51 (71.8%) and 59 (83.1%) of the 71 cases with uninterpretable
      DSC images, respectively. Of the 45 selected patients with interpretable DWI and
      DCE images, the combination of DWI with DCE imaging showed a superior diagnostic
      performance than DWI or DCE imaging alone for differentiating tumor recurrence
      from post-treatment effect (cross-validated AUC: 0.78 versus 0.55 and 0.73 for
      reader 1; cross-validated AUC: 0.78 versus 0.53 and 0.75 for reader 2,
      respectively). Cross-validated accuracy of the single and combined imaging
      parameters also showed the highest for the combination of DWI with DCE MR imaging
      (72.9% for reader 1; 72.5% for reader 2) and the lowest for DWI alone (54.0% for
      reader 1; 56.4% for reader 2). Inter-reader agreement for DCE imaging was higher
      than that for DWI (intraclass correlation coefficient: 0.95 versus 0.87).
      CONCLUSION: DCE MR imaging could be a superior and more reproducible imaging
      biomarker than DWI for differentiating tumor recurrence from post-treatment
      effect in patients with post-treatment glioblastoma when DSC MR images are not
      interpretable.

PMID- 26296087
TI  - Investigation of Overrun-Processed Porous Hyaluronic Acid Carriers in Corneal
      Endothelial Tissue Engineering.
AB  - Hyaluronic acid (HA) is a linear polysaccharide naturally found in the eye and
      therefore is one of the most promising biomaterials for corneal endothelial
      regenerative medicine. This study reports, for the first time, the development of
      overrun-processed porous HA hydrogels for corneal endothelial cell (CEC) sheet
      transplantation and tissue engineering applications. The hydrogel carriers were
      characterized to examine their structures and functions. Evaluations of
      carbodiimide cross-linked air-dried and freeze-dried HA samples were conducted
      simultaneously for comparison. The results indicated that during the fabrication
      of freeze-dried HA discs, a technique of introducing gas bubbles in the aqueous
      biopolymer solutions can be used to enlarge pore structure and prevent dense
      surface skin formation. Among all the groups studied, the overrun-processed
      porous HA carriers show the greatest biological stability, the highest freezable
      water content and glucose permeability, and the minimized adverse effects on
      ionic pump function of rabbit CECs. After transfer and attachment of
      bioengineered CEC sheets to the overrun-processed HA hydrogel carriers, the
      therapeutic efficacy of cell/biopolymer constructs was tested using a rabbit
      model with corneal endothelial dysfunction. Clinical observations including slit
      lamp biomicroscopy, specular microscopy, and corneal thickness measurements
      showed that the construct implants can regenerate corneal endothelium and restore
      corneal transparency at 4 weeks postoperatively. Our findings suggest that cell
      sheet transplantation using overrun-processed porous HA hydrogels offers a new
      way to reconstruct the posterior corneal surface and improve endothelial tissue
      function. 

PMID- 26296088
TI  - Statistical Machines for Trauma Hospital Outcomes Research: Application to the
      PRospective, Observational, Multi-Center Major Trauma Transfusion (PROMMTT)
      Study.
AB  - Improving the treatment of trauma, a leading cause of death worldwide, is of
      great clinical and public health interest. This analysis introduces flexible
      statistical methods for estimating center-level effects on individual outcomes in
      the context of highly variable patient populations, such as those of the
      PRospective, Observational, Multi-center Major Trauma Transfusion study. Ten US
      level I trauma centers enrolled a total of 1,245 trauma patients who survived at
      least 30 minutes after admission and received at least one unit of red blood
      cells. Outcomes included death, multiple organ failure, substantial bleeding, and
      transfusion of blood products. The centers involved were classified as either
      large or small-volume based on the number of massive transfusion patients
      enrolled during the study period. We focused on estimation of parameters inspired
      by causal inference, specifically estimated impacts on patient outcomes related
      to the volume of the trauma hospital that treated them. We defined this
      association as the change in mean outcomes of interest that would be observed if,
      contrary to fact, subjects from large-volume sites were treated at small-volume
      sites (the effect of treatment among the treated). We estimated this parameter
      using three different methods, some of which use data-adaptive machine learning
      tools to derive the outcome models, minimizing residual confounding by reducing
      model misspecification. Differences between unadjusted and adjusted estimators
      sometimes differed dramatically, demonstrating the need to account for
      differences in patient characteristics in clinic comparisons. In addition, the
      estimators based on robust adjustment methods showed potential impacts of
      hospital volume. For instance, we estimated a survival benefit for patients who
      were treated at large-volume sites, which was not apparent in simpler, unadjusted
      comparisons. By removing arbitrary modeling decisions from the estimation process
      and concentrating on parameters that have more direct policy implications, these
      potentially automated approaches allow methodological standardization across
      similar comparativeness effectiveness studies. 

PMID- 26296089
TI  - Psychosocial Care Needs of Melanoma Survivors: Are They Being Met?
AB  - Patients who have survived malignant melanoma for more than five years may lack
      the opportunity to talk about their burden. As a consequence their psychosocial
      care needs remain undetected and available supportive interventions may not be
      utilised. Therefore, the psychosocial burden of this patient group needs to be
      assessed using specific screening instruments. The aim of this study was to
      investigate the psychosocial burden of long-term melanoma survivors, their
      psychosocial care needs and the determinants of these needs. We wanted to find
      out if the use of professional support corresponds to the care needs defined by
      experts. Using the cancer registry of Rhineland-Palatinate, melanoma patients
      diagnosed at least 5 years before the survey were contacted by physicians. N =
      689 former patients completed the Hornheide Questionnaire (short form HQ-S) to
      identify psychosocial support need (scale cut off >= 16 or item-based cut-off
      score) and the potential psychosocial determinants of these needs. Additionally,
      they were asked about their utilisation of the professional support system. More
      than one third (36%) of them was in need for professional psychosocial support.
      The highest burden scores concerned worry about tumour progression. Younger age
      (< 50), higher general fatigue, higher symptom burden, lower general health,
      negative social interactions and unfulfilled information needs were significant
      predictors of the need for psychosocial intervention. Related to the percentage
      of survivors identified as 'in need', the professional support system was
      underused. Further studies should investigate whether using the HQ-S to routinely
      identify burdened melanoma patients could lead to better fulfilment of their
      intervention needs, ultimately enhancing health-related quality of life. 

PMID- 26296090
TI  - A Novel Neurotoxin Gene ar1b Recombination Enhances the Efficiency of Helicoverpa
      armigera Nucleopolyhedrovirus as a Pesticide by Inhibiting the Host Larvae
      Ability to Feed and Grow.
AB  - A recombinant Helicoverpa armigera nucleopolyhedrovirus (HearNPV), Ar1b-HearNPV,
      was constructed and identified as an improved bio-control agent of Helicoverpa
      armigera larvae. The HearNPV polyhedrin promoter was used to express the insect
      specific neurotoxin gene, ar1b, which was originally isolated from the Australian
      funnel-web spider (Atrax robustus). RT-PCR and Western blotting analysis showed
      that both the ar1b transcript and protein were produced successfully in Ar1b
      HearNPV-infected HzAM1 cells. In order to investigate the influence of foreign
      gene insertion in HearNPV, including the ar1b gene, chloramphenicol resistance
      gene, lacZ, kanamycin resistance gene, and the gentamicin resistance gene, two
      virus strains (HZ8-HearNPV and wt-HearNPV) were used as controls in the cell
      transfection analysis. As expected, foreign gene insertion had no impact on
      budded virus production and viral DNA replication. Both optical microscopy and
      electron microscopy observations indicated that the formation of the occlusion
      bodies of recombinant virus was similar to wild type virus. The Ar1b-HearNPV
      infected H. armigera larvae exhibited paralysis and weight loss before dying.
      This recombinant virus also showed a 32.87% decrease in LT50 assays compared with
      the wild type virus. Besides, Ar1b-HearNPV also inhibited host larval growth and
      diet consumption. This inhibition was still significant in the older instar
      larvae treated with the recombinant virus. All of these positive properties of
      this novel recombinant HearNPV provide a further opportunity to develop this
      virus strain into a commercial product to control the cotton bollworm. 

PMID- 26296091
TI  - Interferon-gamma Promotes Inflammation and Development of T-Cell Lymphoma in HTLV
      1 bZIP Factor Transgenic Mice.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) is an etiological agent of several
      inflammatory diseases and a T-cell malignancy, adult T-cell leukemia (ATL). HTLV
      1 bZIP factor (HBZ) is the only viral gene that is constitutively expressed in
      HTLV-1-infected cells, and it has multiple functions on T-cell signaling
      pathways. HBZ has important roles in HTLV-1-mediated pathogenesis, since HBZ
      transgenic (HBZ-Tg) mice develop systemic inflammation and T-cell lymphomas,
      which are similar phenotypes to HTLV-1-associated diseases. We showed previously
      that in HBZ-Tg mice, HBZ causes unstable Foxp3 expression, leading to an increase
      in regulatory T cells (Tregs) and the consequent induction of IFN-gamma-producing
      cells, which in turn leads to the development of inflammation in the mice. In
      this study, we show that the severity of inflammation is correlated with the
      development of lymphomas in HBZ-Tg mice, suggesting that HBZ-mediated
      inflammation is closely linked to oncogenesis in CD4+ T cells. In addition, we
      found that IFN-gamma-producing cells enhance HBZ-mediated inflammation, since
      knocking out IFN-gamma significantly reduced the incidence of dermatitis as well
      as lymphoma. Recent studies show the critical roles of the intestinal microbiota
      in the development of Tregs in vivo. We found that even germ-free HBZ-Tg mice
      still had an increased number of Tregs and IFN-gamma-producing cells, and
      developed dermatitis, indicating that an intrinsic activity of HBZ evokes
      aberrant T-cell differentiation and consequently causes inflammation. These
      results show that immunomodulation by HBZ is implicated in both inflammation and
      oncogenesis, and suggest a causal connection between HTLV-1-associated
      inflammation and ATL. 

PMID- 26296093
TI  - High HIV Prevalence among Asylum Seekers Who Gave Birth in the Netherlands: A
      Nationwide Study Based on Antenatal HIV Tests.
AB  - OBJECTIVES: Asylum seekers are considered to be a particularly vulnerable group
      with respect to HIV. Data on the HIV prevalence among asylum seekers, however,
      are scarce. The aim of this study is to map the HIV prevalence among asylum
      seekers who gave birth in The Netherlands. METHODS: We used a nationwide
      electronic medical records database from the community health services for asylum
      seekers (MOA). The study population consisted of 4,854 women and girls who
      delivered in asylum reception between 2000 and 2008. A unique electronic health
      data base was used and case allocation was based on ICPC-codes. RESULTS: The
      number of women and girls that was HIV positive during their last pregnancy was
      80, of which 79 originated from sub-Saharan Africa. The prevalence for women from
      this region of origin (3.4%) was high compared to women from all other regions of
      origin (0.04%; OR = 90.2; 95%CI 12.5-648.8). The highest HIV prevalence rates
      were found for women from Rwanda (17.0%) and Cameroon (13.2%). HIV prevalence
      rates were higher among women who arrived in reception without partner (OR =
      1.82; 95%CI 0.75-4.44) and unaccompanied minors (OR = 2.59; 95%CI 0.79-8.49),
      compared to women who arrived in reception with partner. CONCLUSIONS: We conclude
      that, among asylum-seeking women from sub-Saharan Africa giving birth in The
      Netherlands, the HIV prevalence is high compared to the host population. For
      women from other regions of origin, the prevalence is at the same level as in the
      host population. The high HIV prevalence underlines the importance of preventive
      interventions and voluntary HIV testing for sub-Saharan African asylum seekers as
      from shortly after arrival.

PMID- 26296092
TI  - Pharmacokinetics and Pharmacodynamics with Extended Dosing of CC-486 in Patients
      with Hematologic Malignancies.
AB  - CC-486 (oral azacitidine) is an epigenetic modifier in development for patients
      with myelodysplastic syndromes and acute myeloid leukemia. In part 1 of this two
      part study, a 7-day CC-486 dosing schedule showed clinical activity, was
      generally well tolerated, and reduced DNA methylation. Extending dosing of CC-486
      beyond 7 days would increase duration of azacitidine exposure. We hypothesized
      that extended dosing would therefore provide more sustained epigenetic activity.
      Reported here are the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of
      CC-486 extended dosing schedules in patients with myelodysplastic syndromes
      (MDS), chronic myelomonocytic leukemia (CMML) or acute myeloid leukemia (AML)
      from part 2 of this study. PK and/or PD data were available for 59 patients who
      were sequentially assigned to 1 of 4 extended CC-486 dosing schedules: 300mg once
      daily or 200mg twice-daily for 14 or 21 days per 28-day cycle. Both 300mg once
      daily schedules and the 200mg twice-daily 21-day schedule significantly (all P <
      .05) reduced global DNA methylation in whole blood at all measured time points
      (days 15, 22, and 28 of the treatment cycle), with sustained hypomethylation at
      cycle end compared with baseline. CC-486 exposures and reduced DNA methylation
      were significantly correlated. Patients who had a hematologic response had
      significantly greater methylation reductions than non-responding patients. These
      data demonstrate that extended dosing of CC-486 sustains epigenetic effects
      through the treatment cycle. TRIAL REGISTRATION: ClinicalTrials.gov NCT00528983.

PMID- 26296094
TI  - CLCA1 and TMEM16A: the link towards a potential cure for airway diseases.
AB  - The hallmark traits of chronic obstructive airway diseases are inflammation,
      airway constriction due to hyperreactivity and mucus overproduction. The current
      common treatments for asthma and chronic obstructive pulmonary disease target the
      first two traits with none currently targeting mucus overproduction. The main
      source of obstructive mucus production is mucus cell metaplasia (MCM), the
      transdifferentiation of airway epithelial cells into mucus-producing goblet
      cells, in the small airways. Our current understanding of MCM is profusely
      incomplete. Few of the molecular players involved in driving MCM in humans have
      been identified and for many of those that have, their functions and mechanisms
      are unknown. This fact has limited the development of therapeutics that target
      mucus overproduction by inhibiting MCM. Current work in the field is aiming to
      change that. 

PMID- 26296095
TI  - Gender and Age Differences in Hourly and Daily Patterns of Sedentary Time in
      Older Adults Living in Retirement Communities.
AB  - BACKGROUND: Total sedentary time varies across population groups with important
      health consequences. Patterns of sedentary time accumulation may vary and have
      differential health risks. The purpose of this study is to describe sedentary
      patterns of older adults living in retirement communities and illustrate gender
      and age differences in those patterns. METHODS: Baseline accelerometer data from
      307 men and women (mean age = 84+/-6 years) who wore ActiGraph GT3X+
      accelerometers for >= 4 days as part of a physical activity intervention were
      classified into bouts of sedentary time (<100 counts per minute). Linear mixed
      models were used to account for intra-person and site-level clustering. Daily and
      hourly summaries were examined in mutually non-exclusive bouts of sedentary time
      that were 1+, 5+, 10+, 20+, 30+, 40+, 50+, 60+, 90+ and 120+ minutes in duration.
      Variations by time of day, age and gender were explored. RESULTS: Men accumulated
      more sedentary time than women in 1+, 5+, 10+, 20+, 30+, 40+, 50+ and 60+ minute
      bouts; the largest gender-differences were observed in 10+ and 20+ minute bouts.
      Age was positively associated with sedentary time, but only in bouts of 10+, 20+,
      30+, and 40+ minutes. Women had more daily 1+ minute sedentary bouts than men
      (71.8 vs. 65.2), indicating they break up sedentary time more often. For men and
      women, a greater proportion of time was spent being sedentary during later hours
      of the day than earlier. Gender differences in intra-day sedentary time were
      observed during morning hours with women accumulating less sedentary time overall
      and having more 1+ minute bouts. CONCLUSIONS: Patterns identified using bouts of
      sedentary time revealed gender and age differences in the way in which sedentary
      time was accumulated by older adults in retirement communities. Awareness of
      these patterns can help interventionists better target sedentary time and may aid
      in the identification of health risks associated with sedentary behavior. Future
      studies should investigate the impact of patterns of sedentary time on healthy
      aging, disease, and mortality.

PMID- 26296097
TI  - Engaging Environments Enhance Motor Skill Learning in a Computer Gaming Task.
AB  - Engagement during practice can motivate a learner to practice more, hence having
      indirect effects on learning through increased practice. However, it is not known
      whether engagement can also have a direct effect on learning when the amount of
      practice is held constant. To address this question, 40 participants played a
      video game that contained an embedded repeated sequence component, under either
      highly engaging conditions (the game group) or mechanically identical but less
      engaging conditions (the sterile group). The game environment facilitated
      retention over a 1-week interval. Specifically, the game group improved in both
      speed and accuracy for random and repeated trials, suggesting a general motor
      related improvement, rather than a specific influence of engagement on implicit
      sequence learning. These data provide initial evidence that increased engagement
      during practice has a direct effect on generalized learning, improving retention
      and transfer of a complex motor skill. 

PMID- 26296096
TI  - Behavior and Properties of Mature Lytic Granules at the Immunological Synapse of
      Human Cytotoxic T Lymphocytes.
AB  - Killing of virally infected cells or tumor cells by cytotoxic T lymphocytes
      requires targeting of lytic granules to the junction between the CTL and its
      target. We used whole-cell patch clamp to measure the cell capacitance at fixed
      intracellular [Ca2+] to study fusion of lytic granules in human CTLs. Expression
      of a fluorescently labeled human granzyme B construct allowed identification of
      lytic granule fusion using total internal reflection fluorescence microscopy. In
      this way capacitance steps due to lytic granule fusion were identified. Our goal
      was to determine the size of fusing lytic granules and to describe their behavior
      at the plasma membrane. On average, 5.02 +/- 3.09 (mean +/- s.d.) lytic granules
      were released per CTL. The amplitude of lytic granule fusion events was ~ 3.3 fF
      consistent with a diameter of about 325 nm. Fusion latency was biphasic with time
      constants of 15.9 and 106 seconds. The dwell time of fusing lytic granules was
      exponentially distributed with a mean dwell time of 28.5 seconds. Fusion ended in
      spite of the continued presence of granules at the immune synapse. The mobility
      of fusing granules at the membrane was indistinguishable from that of lytic
      granules which failed to fuse. While dwelling at the plasma membrane lytic
      granules exhibit mobility consistent with docking interspersed with short periods
      of greater mobility. The failure of lytic granules to fuse when visible in TIRF
      at the membrane may indicate that a membrane-confined reaction is rate limiting. 

PMID- 26296099
TI  - Tracking rural-to-urban migration in China: Lessons from the 2005 inter-census
      population survey.
AB  - We examined migration in China using the 2005 inter-census population survey, in
      which migrants were registered at both their place of original (hukou) residence
      and at their destination. We find evidence that the estimated number of internal
      migrants in China is extremely sensitive to the enumeration method. We estimate
      that the traditional destination-based survey method fails to account for more
      than a third of migrants found using comparable origin-based methods. The
      'missing' migrants are disproportionately young, male, and holders of rural
      hukou. We find that origin-based methods are more effective at capturing migrants
      who travel short distances for short periods, whereas destination-based methods
      are more effective when entire households have migrated and no remaining family
      members are located at the hukou location. We conclude with a set of policy
      recommendations for the design of population surveys in countries with large
      migrant populations. 

PMID- 26296098
TI  - Targeting breast cancer with sugar-coated carbon nanotubes.
AB  - AIMS: To evaluate the use of glucosamine functionalized multiwalled carbon
      nanotubes (glyco-MWCNTs) for breast cancer targeting. MATERIALS & METHODS: Two
      types of glucosamine functionalized MWCNTs were developed (covalently linked
      glucosamine and non-covalently phospholipid-glucosamine coated) and evaluated for
      their potential to bind and target breast cancer cells in vitro and in vivo.
      RESULTS & CONCLUSION: Binding of glyco-MWCNTs in breast cancer cells is mediated
      by specific interaction with glucose transporters. Glyco-MWCNTs prepared by non
      covalent coating with phospholipid-glucosamine displayed an extended blood
      circulation time, delayed urinary clearance, low tissue retention and increased
      breast cancer tumor accumulation in vivo. These studies lay the foundation for
      development of a cancer diagnostic agent based upon glyco-MWCNTs with the
      potential for superior accuracy over current radiopharmaceuticals.

PMID- 26296100
TI  - Role of Sacrificial Protein-Metal Bond Exchange in Mussel Byssal Thread Self
      Healing.
AB  - Marine mussels tether to seashore surfaces with byssal threads, proteinaceous
      fibers that effectively dissipate energy from crashing waves. Protein-metal
      coordination bonds have been proposed to contribute to the characteristic
      mechanical and self-healing properties of byssal threads; however, very little is
      understood about how these cross-links function at the molecular level. In the
      present study, combined Raman and X-ray absorption spectroscopy (XAS)
      measurements were employed to confirm the presence of protein-Zn(2+) coordination
      bonds in the mussel byssus and to monitor transitions in the coordination
      structure during thread deformation and self-healing. Results indicate that
      Zn(2+) coordination bonds, primarily mediated via histidine, are ruptured during
      thread yield and reformed immediately following thread relaxation. Mechanical
      healing, on the other hand, is correlated with the transition toward shorter
      coordination bond lengths. Calculation of the healing activation energy suggests
      that protein-Zn bond exchange provides a primary rate-limiting step during
      healing. 

PMID- 26296102
TI  - Probing Contaminant Transport to and from Clay Surfaces in Organic Solvents and
      Water Using Solution Calorimetry.
AB  - Clays, in tailings, are a significant ongoing environmental concern in the mining
      and oilsands production industries, and clay rehabilitation following
      contamination poses challenges episodically. Understanding the fundamentals of
      clay behavior can lead to better environmental impact mitigation strategies.
      Systematic calorimetric measurements are shown to provide a framework for parsing
      the synergistic and antagonistic impacts of trace (i.e., parts per million level)
      components on the surface compositions of clays. The enthalpy of solution of as
      received and "contaminated" clays, in as-received and "contaminated" organic
      solvents and water, at 60  degrees C and atmospheric pressure, provides important
      illustrative examples. Clay contamination included pre-saturation of clays with
      water and organic liquids. Solvent contamination included the addition of trace
      water to organic solvents and trace organic liquids to water. Enthalpy of
      solution outcomes are interpreted using a quantitative mass and energy balance
      modeling framework that isolates terms for solvent and trace contaminant
      sorption/desorption and surface energy effects. Underlying surface energies are
      shown to dominate the energetics of the solvent-clay interaction, and organic
      liquids as solvents or as trace contaminants are shown to displace water from as
      received clay surfaces. This approach can be readily extended to include pH,
      salts, or other effects and is expected to provide mechanistic and quantitative
      insights underlying the stability of clays in tailings ponds and the behaviors of
      clays in diverse industrial and natural environments. 

PMID- 26296101
TI  - Focusing on shared subpockets - new developments in fragment-based drug
      discovery.
AB  - INTRODUCTION: Protein-protein interactions (PPIs) are important targets for
      understanding fundamental biology and for the development of therapeutic agents.
      Based on different physicochemical properties, numerous pieces of software (e.g.,
      POCKETQUERY, ANCHORQUERY and FTMap) have been reported to find pockets on protein
      surfaces and have applications in facilitating the design and discovery of small
      molecular-weight compounds that bind to these pockets. AREAS COVERED: The authors
      discuss a pocket-centric method of analyzing PPI interfaces, which prioritize
      their pockets for small-molecule drug discovery and the importance of
      multicomponent reaction chemistry as starting points for undruggable targets. The
      authors also provide their perspectives on the field. EXPERT OPINION: Only the
      tight interplay of efficient computational methods capable of screening a large
      chemical space and fast synthetic chemistry will lead to progress in the rational
      design of PPI antagonists in the future. Early drug discovery platforms will also
      benefit from efficient rapid feedback loops from early clinical research back to
      molecular design and the medicinal chemistry bench.

PMID- 26296103
TI  - Squeezing and Entanglement of Density Oscillations in a Bose-Einstein Condensate.
AB  - The dispersive interaction of atoms and a far-detuned light field allows
      nondestructive imaging of the density oscillations in Bose-Einstein condensates.
      Starting from a ground state condensate, we investigate how the measurement
      backaction leads to squeezing and entanglement of the quantized density
      oscillations. We show that properly timed, stroboscopic imaging and feedback can
      be used to selectively address specific eigenmodes and avoid excitation of
      nontargeted modes of the system. 

PMID- 26296104
TI  - Time-Delayed Quantum Feedback Control.
AB  - A theory of time-delayed coherent quantum feedback is developed. More
      specifically, we consider a quantum system coupled to a bosonic reservoir
      creating a unidirectional feedback loop. It is shown that the dynamics can be
      mapped onto a fictitious series of cascaded quantum systems, where the system is
      driven by past versions of itself. The derivation of this model relies on a
      tensor network representation of the system-reservoir time propagator. For
      concreteness, this general theory is applied to a driven two-level atom
      scattering into a coherent feedback loop. We demonstrate how delay effects can
      qualitatively change the dynamics of the atom and how quantum control can be
      implemented in the presence of time delays. 

PMID- 26296105
TI  - Robust Characterization of Loss Rates.
AB  - Many physical implementations of qubits-including ion traps, optical lattices and
      linear optics-suffer from loss. A nonzero probability of irretrievably losing a
      qubit can be a substantial obstacle to fault-tolerant methods of processing
      quantum information, requiring new techniques to safeguard against loss that
      introduce an additional overhead that depends upon the loss rate. Here we present
      a scalable and platform-independent protocol for estimating the average loss rate
      (averaged over all input states) resulting from an arbitrary Markovian noise
      process, as well as an independent estimate of detector efficiency. Moreover, we
      show that our protocol gives an additional constraint on estimated parameters
      from randomized benchmarking that improves the reliability of the estimated error
      rate and provides a new indicator for non-Markovian signatures in the
      experimental data. We also derive a bound for the state-dependent loss rate in
      terms of the average loss rate. 

PMID- 26296106
TI  - Light Dark Matter from Forbidden Channels.
AB  - Dark matter (DM) may be a thermal relic that annihilates into heavier states in
      the early universe. This forbidden DM framework accommodates a wide range of DM
      masses from keV to weak scales. An exponential hierarchy between the DM mass and
      the weak scale follows from the exponential suppression of the thermally averaged
      cross section. Stringent constraints from the cosmic microwave background are
      evaded because annihilations turn off at late times. We provide an example where
      DM annihilates into dark photons, which is testable through large DM self
      interactions and direct detection. 

PMID- 26296107
TI  - Six-Dimensional Superconformal Theories and their Compactifications from Type IIA
      Supergravity.
AB  - We describe three analytic classes of infinitely many AdS(d) supersymmetric
      solutions of massive IIA supergravity, for d=7,5,4. The three classes are related
      by simple universal maps. For example, the AdS(7)*M(3) solutions (where M(3) is
      topologically S(3)) are mapped to AdS(5)*Sigma(2)*M(3)', where Sigma(2) is a
      Riemann surface of genus g>=2 and the metric on M(3)' is obtained by distorting
      M(3) in a certain way. The solutions can have localized D6 or O6 sources, as well
      as an arbitrary number of D8-branes. The AdS(7) case (previously known only
      numerically) is conjecturally dual to an NS5-D6-D8 system. The field theories in
      three and four dimensions are not known, but their number of degrees of freedom
      can be computed in the supergravity approximation. The AdS(4) solutions have
      numerical "attractor" generalizations that might be useful for flux
      compactification purposes.

PMID- 26296109
TI  - Penguin Contributions to CP Phases in B(d,s) Decays to Charmonium.
AB  - The precision of the CP phases 2beta and 2beta(s) determined from the mixing
      induced CP asymmetries in B(d)->J/psiK(S) and B(s)->J/psiphi, respectively, is
      limited by the unknown long-distance contribution of a penguin diagram involving
      up quarks. The penguin contribution is expected to be comparable in size to the
      precision of the LHCb and Belle II experiments and, therefore, limits the
      sensitivity of the measured quantities to new physics. We analyze the infrared
      QCD structure of this contribution and find that all soft and collinear
      divergences either cancel between different diagrams or factorize into matrix
      elements of local four-quark operators up to terms suppressed by
      Lambda(QCD)/m(psi), where m(psi) denotes the J/psi mass. Our results, which are
      based on an operator product expansion, allow us to calculate the penguin-to-tree
      ratio P/T in terms of the matrix elements of these operators and to constrain the
      penguin contribution to the phase 2beta as |Deltaphi(d)|<=0.68 degrees . The
      penguin contribution to 2beta(s) is bounded as |Deltaphi(s)(0)|<=0.97 degrees ,
      |Deltaphi(s)(?)|<=1.22 degrees , and |Deltaphi(s)(?)|<=0.99 degrees  for the case
      of longitudinal, parallel, and perpendicular phi and J/psi polarizations,
      respectively. Further, we place bounds on |Deltaphi(d)| for B(d)->psi(2S)K(S) and
      the polarization amplitudes in B(d)->J/psiK(*). In our approach, it is further
      possible to constrain P/T for decays in which P/T is Cabibbo unsuppressed, and we
      derive upper limits on the penguin contribution to the mixing-induced CP
      asymmetries in B(d)->J/psipi(0), B(d)->J/psirho(0), B(s)->J/psiK(S), and B(s)
      >J/psiK(*). For all studied decay modes, we also constrain the sizes of the
      direct CP asymmetries.

PMID- 26296110
TI  - Electric Dipole Moment of the Neutron from 2+1 Flavor Lattice QCD.
AB  - We compute the electric dipole moment d(n) of the neutron from a fully dynamical
      simulation of lattice QCD with 2+1 flavors of clover fermions and nonvanishing
      theta term. The latter is rotated into a pseudoscalar density in the fermionic
      action using the axial anomaly. To make the action real, the vacuum angle theta
      is taken to be purely imaginary. The physical value of dd(n) is obtained by
      analytic continuation. We find d(n)=-3.9(2)(9)*10(-16) theta  e cm, which, when
      combined with the experimental limit on d(n), leads to the upper bound
      |theta|?7.4*10(-11).

PMID- 26296111
TI  - W-Boson Production in Association with a Jet at Next-to-Next-to-Leading Order in
      Perturbative QCD.
AB  - We present the complete calculation of W-boson production in association with a
      jet in hadronic collisions through next-to-next-to-leading order (NNLO) in
      perturbative QCD. To cancel infrared divergences, we discuss a new subtraction
      method that exploits the fact that the N-jettiness event-shape variable fully
      captures the singularity structure of QCD amplitudes with final-state partons.
      This method holds for processes with an arbitrary number of jets and is easily
      implemented into existing frameworks for higher-order calculations. We present
      initial phenomenological results for W+jet production at the LHC. The NNLO
      corrections are small and lead to a significantly reduced theoretical error,
      opening the door to precision measurements in the W+jet channel at the LHC. 

PMID- 26296112
TI  - Direct Measurement of the Mass Difference of (163)Ho and (163)Dy Solves the Q
      Value Puzzle for the Neutrino Mass Determination.
AB  - The atomic mass difference of (163)Ho and (163)Dy has been directly measured with
      the Penning-trap mass spectrometer SHIPTRAP applying the novel phase-imaging ion
      cyclotron-resonance technique. Our measurement has solved the long-standing
      problem of large discrepancies in the Q value of the electron capture in (163)Ho
      determined by different techniques. Our measured mass difference shifts the
      current Q value of 2555(16) eV evaluated in the Atomic Mass Evaluation 2012 [G.
      Audi et al., Chin. Phys. C 36, 1157 (2012)] by more than 7sigma to
      2833(30(stat))(15(sys)) eV/c(2). With the new mass difference it will be
      possible, e.g., to reach in the first phase of the ECHo experiment a statistical
      sensitivity to the neutrino mass below 10 eV, which will reduce its present upper
      limit by more than an order of magnitude.

PMID- 26296114
TI  - Inverse Kinematic Study of the (26g)Al(d,p)(27)Al Reaction and Implications for
      Destruction of (26)Al in Wolf-Rayet and Asymptotic Giant Branch Stars.
AB  - In Wolf-Rayet and asymptotic giant branch (AGB) stars, the (26g)Al(p,gamma)(27)Si
      reaction is expected to govern the destruction of the cosmic gamma-ray emitting
      nucleus (26)Al. The rate of this reaction, however, is highly uncertain due to
      the unknown properties of key resonances in the temperature regime of hydrogen
      burning. We present a high-resolution inverse kinematic study of the
      (26g)Al(d,p)(27)Al reaction as a method for constraining the strengths of key
      astrophysical resonances in the (26g)Al(p,gamma)(27)Si reaction. In particular,
      the results indicate that the resonance at E(r)=127  keV in (27)Si determines the
      entire (26g)Al(p,gamma)(27)Si reaction rate over almost the complete temperature
      range of Wolf-Rayet stars and AGB stars.

PMID- 26296115
TI  - Energetics and Control of Ultracold Isotope-Exchange Reactions between
      Heteronuclear Dimers in External Fields.
AB  - We show that isotope-exchange reactions between ground-state alkali-metal,
      alkaline-earth-metal, and lanthanide heteronuclear dimers consisting of two
      isotopes of the same atom are exothermic with an energy change in the range of 1
      8000 MHz, thus resulting in cold or ultracold products. For these chemical
      reactions, there are only one rovibrational and at most several hyperfine
      possible product states. The number and energetics of open and closed reactive
      channels can be controlled by the laser and magnetic fields. We suggest a laser
      induced isotope- and state-selective Stark shift control to tune the exothermic
      isotope-exchange reactions to become endothermic, thus providing the ground for
      testing models of the chemical reactivity. The present proposal opens the way for
      studying the state-to-state dynamics of ultracold chemical reactions beyond the
      universal limit with a meaningful control over the quantum states of both
      reactants and products. 

PMID- 26296113
TI  - Enhanced gamma-Ray Emission from Neutron Unbound States Populated in beta Decay.
AB  - Total absorption spectroscopy is used to investigate the beta-decay intensity to
      states above the neutron separation energy followed by gamma-ray emission in
      (87,88)Br and (94)Rb. Accurate results are obtained thanks to a careful control
      of systematic errors. An unexpectedly large gamma intensity is observed in all
      three cases extending well beyond the excitation energy region where neutron
      penetration is hindered by low neutron energy. The gamma branching as a function
      of excitation energy is compared to Hauser-Feshbach model calculations. For
      (87)Br and (88)Br the gamma branching reaches 57% and 20%, respectively, and
      could be explained as a nuclear structure effect. Some of the states populated in
      the daughter can only decay through the emission of a large orbital angular
      momentum neutron with a strongly reduced barrier penetrability. In the case of
      neutron-rich (94)Rb the observed 4.5% branching is much larger than the
      calculations performed with standard nuclear statistical model parameters, even
      after proper correction for fluctuation effects on individual transition widths.
      The difference can be reconciled by introducing an enhancement of 1 order of
      magnitude in the photon strength to neutron strength ratio. An increase in the
      photon strength function of such magnitude for very neutron-rich nuclei, if it
      proves to be correct, leads to a similar increase in the (n,gamma) cross section
      that would have an impact on r process abundance calculations.

PMID- 26296116
TI  - Superradiance for Atoms Trapped along a Photonic Crystal Waveguide.
AB  - We report observations of superradiance for atoms trapped in the near field of a
      photonic crystal waveguide (PCW). By fabricating the PCW with a band edge near
      the D(1) transition of atomic cesium, strong interaction is achieved between
      trapped atoms and guided-mode photons. Following short-pulse excitation, we
      record the decay of guided-mode emission and find a superradiant emission rate
      scaling as Gamma(SR)?NGamma(1D) for average atom number 0.19?N?2.6 atoms, where
      Gamma(1D)/Gamma'=1.0+/-0.1 is the peak single-atom radiative decay rate into the
      PCW guided mode, and Gamma' is the radiative decay rate into all the other
      channels. These advances provide new tools for investigations of photon-mediated
      atom-atom interactions in the many-body regime.

PMID- 26296117
TI  - Synchronization as Aggregation: Cluster Kinetics of Pulse-Coupled Oscillators.
AB  - We consider models of identical pulse-coupled oscillators with global
      interactions. Previous work showed that under certain conditions such systems
      always end up in sync, but did not quantify how small clusters of synchronized
      oscillators progressively coalesce into larger ones. Using tools from the study
      of aggregation phenomena, we obtain exact results for the time-dependent
      distribution of cluster sizes as the system evolves from disorder to synchrony. 

PMID- 26296118
TI  - Droplets in Microchannels: Dynamical Properties of the Lubrication Film.
AB  - We study the motion of droplets in a confined, micrometric geometry, by focusing
      on the lubrication film between a droplet and a wall. When capillary forces
      dominate, the lubrication film thickness evolves nonlinearly with the capillary
      number due to the viscous dissipation between the meniscus and the wall. However,
      this film may become thin enough (tens of nanometers) that intermolecular forces
      come into play and affect classical scalings. Our experiments yield highly
      resolved topographies of the shape of the interface and allow us to bring new
      insights into droplet dynamics in microfluidics. We report the novel
      characterization of two dynamical regimes as the capillary number increases: (i)
      at low capillary numbers, the film thickness is constant and set by the
      disjoining pressure, while (ii) above a critical capillary number, the interface
      behavior is well described by a viscous scenario. At a high surfactant
      concentration, structural effects lead to the formation of patterns on the
      interface, which can be used to trace the interface velocity, that yield direct
      confirmation of the boundary condition in the viscous regime. 

PMID- 26296119
TI  - Ion Acceleration Using Relativistic Pulse Shaping in Near-Critical-Density
      Plasmas.
AB  - Ultraintense laser pulses with a few-cycle rising edge are ideally suited to
      accelerating ions from ultrathin foils, and achieving such pulses in practice
      represents a formidable challenge. We show that such pulses can be obtained using
      sufficiently strong and well-controlled relativistic nonlinearities in spatially
      well-defined near-critical-density plasmas. The resulting ultraintense pulses
      with an extremely steep rising edge give rise to significantly enhanced carbon
      ion energies consistent with a transition to radiation pressure acceleration. 

PMID- 26296120
TI  - Parafermionic Zero Modes in Ultracold Bosonic Systems.
AB  - Exotic topologically protected zero modes with parafermionic statistics (also
      called fractionalized Majorana modes) have been proposed to emerge in devices
      fabricated from a fractional quantum Hall system and a superconductor. The
      fractionalized statistics of these modes takes them an important step beyond the
      simplest non-Abelian anyons, Majorana fermions. Building on recent advances
      towards the realization of fractional quantum Hall states of bosonic ultracold
      atoms, we propose a realization of parafermions in a system consisting of Bose
      Einstein-condensate trenches within a bosonic fractional quantum Hall state. We
      show that parafermionic zero modes emerge at the end points of the trenches and
      give rise to a topologically protected degeneracy. We also discuss methods for
      preparing and detecting these modes. 

PMID- 26296121
TI  - Electronic Origins of Anomalous Twin Boundary Energies in Hexagonal Close Packed
      Transition Metals.
AB  - Density-functional-theory calculations of twin-boundary energies in hexagonal
      close packed metals reveal anomalously low values for elemental Tc and Re, which
      can be lowered further by alloying with solutes that reduce the electron per atom
      ratio. The anomalous behavior is linked to atomic geometries in the interface
      similar to those observed in bulk tetrahedrally close packed phases. The results
      establish a link between twin-boundary energetics and the theory of bulk
      structural stability in transition metals that may prove useful in controlling
      mechanical behavior in alloy design. 

PMID- 26296122
TI  - Intramolecular Force Contrast and Dynamic Current-Distance Measurements at Room
      Temperature.
AB  - Scanning probe microscopy can be used to probe the internal atomic structure of
      flat organic molecules. This technique requires an unreactive tip and has, until
      now, been demonstrated only at liquid helium and liquid nitrogen temperatures. We
      demonstrate intramolecular and intermolecular force contrast at room temperature
      on PTCDA molecules adsorbed on a Ag/Si(111)-(?[3]*?[3]) surface. The oscillating
      force sensor allows us to dynamically measure the vertical decay constant of the
      tunneling current. The precision of this method is increased by quantifying the
      transimpedance of the current to voltage converter and accounting for the tip
      oscillation. This measurement yields a clear contrast between neighboring
      molecules, which we attribute to the different charge states.

PMID- 26296123
TI  - Landau Theory of Helical Fermi Liquids.
AB  - We construct a phenomenological Landau theory for the two-dimensional helical
      Fermi liquid found on the surface of a three-dimensional time-reversal invariant
      topological insulator. In the presence of rotation symmetry, interactions between
      quasiparticles are described by ten independent Landau parameters per angular
      momentum channel, by contrast with the two (symmetric and antisymmetric) Landau
      parameters for a conventional spin-degenerate Fermi liquid. We project
      quasiparticle states onto the Fermi surface and obtain an effectively spinless,
      projected Landau theory with a single projected Landau parameter per angular
      momentum channel that captures the spin-momentum locking or nontrivial Berry
      phase of the Fermi surface. As a result of this nontrivial Berry phase,
      projection to the Fermi surface can increase or lower the angular momentum of the
      quasiparticle interactions. We derive equilibrium properties, criteria for Fermi
      surface instabilities, and collective mode dispersions in terms of the projected
      Landau parameters. We briefly discuss experimental means of measuring projected
      Landau parameters. 

PMID- 26296124
TI  - Efficient Explicitly Correlated Many-Electron Perturbation Theory for Solids:
      Application to the Schottky Defect in MgO.
AB  - We introduce a novel and efficient explicitly correlated implementation of second
      order perturbation theory for solids. The required three-electron integrals are
      computed directly using a plane wave basis set. We parametrize the employed
      correlation factors using results previously obtained for a finite uniform
      electron gas simulation cell. We demonstrate for a range of solids that basis set
      converged correlation energies, equilibrium volumes, and bulk moduli can be
      obtained efficiently in this theory using a few ten orbitals per atom. To stretch
      the capabilities of this novel method we compute the Schottky defect formation
      energy in MgO, studying systems with 54 atoms in the supercell. We verify the
      accuracy of the calculated formation energies using the more accurate coupled
      cluster singles and doubles theory. Furthermore, we discuss other potential
      applications for the derived and implemented expressions such as an occupied
      orbital only correlation energy functional. 

PMID- 26296125
TI  - Linear Scaling of the Exciton Binding Energy versus the Band Gap of Two
      Dimensional Materials.
AB  - The exciton is one of the most crucial physical entities in the performance of
      optoelectronic and photonic devices, and widely varying exciton binding energies
      have been reported in different classes of materials. Using first-principles
      calculations within the GW-Bethe-Salpeter equation approach, here we investigate
      the excitonic properties of two recently discovered layered materials:
      phosphorene and graphene fluoride. We first confirm large exciton binding
      energies of, respectively, 0.85 and 2.03 eV in these systems. Next, by comparing
      these systems with several other representative two-dimensional materials, we
      discover a striking linear relationship between the exciton binding energy and
      the band gap and interpret the existence of the linear scaling law within a
      simple hydrogenic picture. The broad applicability of this novel scaling law is
      further demonstrated by using strained graphene fluoride. These findings are
      expected to stimulate related studies in higher and lower dimensions, potentially
      resulting in a deeper understanding of excitonic effects in materials of all
      dimensionalities. 

PMID- 26296126
TI  - Surface and Step Conductivities on Si(111) Surfaces.
AB  - Four-point measurements using a multitip scanning tunneling microscope are
      carried out in order to determine surface and step conductivities on Si(111)
      surfaces. In a first step, distance-dependent four-point measurements in the
      linear configuration are used in combination with an analytical three-layer model
      for charge transport to disentangle the 2D surface conductivity from nonsurface
      contributions. A termination of the Si(111) surface with either Bi or H results
      in the two limiting cases of a pure 2D or 3D conductance, respectively. In order
      to further disentangle the surface conductivity of the step-free surface from the
      contribution due to atomic steps, a square four-probe configuration is applied as
      a function of the rotation angle. In total, this combined approach leads to an
      atomic step conductivity of sigma(step)=(29+/-9)  Omega(-1) m(-1) and to a step
      free surface conductivity of sigma(surf)=(9+/-2)*10(-6)  Omega(-1)/? for the
      Si(111)-(7*7) surface.

PMID- 26296127
TI  - Dynamic Reorganization of Vortex Matter into Partially Disordered Lattices.
AB  - We report structural evidence of dynamic reorganization in vortex matter in clean
      NbSe(2) by joint small-angle neutron scattering and ac susceptibility
      measurements. The application of oscillatory forces in a transitional region near
      the order-disorder transition results in robust bulk vortex lattice
      configurations with an intermediate degree of disorder. These dynamically
      originated configurations correlate with intermediate pinning responses
      previously observed, resolving a long-standing debate regarding the origin of
      such responses.

PMID- 26296128
TI  - Large Superconducting Spin Valve Effect and Ultrasmall Exchange Splitting in
      Epitaxial Rare-Earth-Niobium Trilayers.
AB  - Epitaxial Ho/Nb/Ho and Dy/Nb/Dy superconducting spin valves show a reversible
      change in the zero-field critical temperature (DeltaT(c0)) of ~400  mK and an
      infinite magnetoresistance on changing the relative magnetization of the Ho or Dy
      layers. Unlike transition-metal superconducting spin valves, which show much
      smaller DeltaT(c0) values, our results can be quantitatively modeled. However,
      the fits require an extraordinarily low induced exchange splitting which is
      dramatically lower than known values for rare-earth Fermi-level electrons,
      implying that new models for the magnetic proximity effect may be required.

PMID- 26296129
TI  - Strain Induced Vortex Core Switching in Planar Magnetostrictive Nanostructures.
AB  - The dynamics of magnetic vortex cores is of great interest because the gyrotropic
      mode has applications in spin torque driven magnetic microwave oscillators, and
      also provides a means to flip the direction of the core for use in magnetic
      storage devices. Here, we propose a new means of stimulating magnetization
      reversal of the vortex core by applying a time-varying strain gradient to planar
      structures of the magnetostrictive material Fe(81)Ga(19) (Galfenol), coupled to
      an underlying piezoelectric layer. Using micromagnetic simulations we have shown
      that the vortex core state can be deterministically reversed by electric field
      control of the time-dependent strain-induced anisotropy.

PMID- 26296108
TI  - Search for Resonances Decaying to Top and Bottom Quarks with the CDF Experiment.
AB  - We report on a search for charged massive resonances decaying to top (t) and
      bottom (b) quarks in the full data set of proton-antiproton collisions at a
      center-of-mass energy of ?[s]=1.96  TeV collected by the CDF II detector at the
      Tevatron, corresponding to an integrated luminosity of 9.5  fb(-1). No
      significant excess above the standard model background prediction is observed. We
      set 95% Bayesian credibility mass-dependent upper limits on the heavy charged
      particle production cross section times branching ratio to tb. Using a standard
      model extension with a W'->tb and left-right-symmetric couplings as a benchmark
      model, we constrain the W' mass and couplings in the 300-900  GeV/c(2) range. The
      limits presented here are the most stringent for a charged resonance with mass in
      the range 300-600  GeV/c(2) decaying to top and bottom quarks.

PMID- 26296130
TI  - Towards Scalable Entangled Photon Sources with Self-Assembled InAs/GaAs Quantum
      Dots.
AB  - The biexciton cascade process in self-assembled quantum dots (QDs) provides an
      ideal system for realizing deterministic entangled photon-pair sources, which are
      essential to quantum information science. The entangled photon pairs have
      recently been generated in experiments after eliminating the fine-structure
      splitting (FSS) of excitons using a number of different methods. Thus far,
      however, QD-based sources of entangled photons have not been scalable because the
      wavelengths of QDs differ from dot to dot. Here, we propose a wavelength-tunable
      entangled photon emitter mounted on a three-dimensional stressor, in which the
      FSS and exciton energy can be tuned independently, thereby enabling photon
      entanglement between dissimilar QDs. We confirm these results via atomistic
      pseudopotential calculations. This provides a first step towards future
      realization of scalable entangled photon generators for quantum information
      applications. 

PMID- 26296131
TI  - Line Degeneracy and Strong Spin-Orbit Coupling of Light with Bulk Bianisotropic
      Metamaterials.
AB  - Propagation of light in a medium is dictated by equifrequency surfaces (EFSs),
      which play a similar role as Fermi surfaces for electrons in crystals.
      Engineering the equifrequency surface of light through structuring a photonic
      medium enables superior control over light propagation that goes beyond natural
      materials. In this Letter, we show that a bulk metamaterial with a suitably
      designed bianisotropy can exhibit line degeneracy in its EFSs that consist of two
      ellipsoids of opposite helicity states intersecting with each other. Very
      interestingly, light propagating along the direction of the line degeneracy
      experiences strong spin-dependent photon deflection, or optical spin Hall effect,
      which may lead to applications in optical signal processing and spin-optical
      manipulations. We provide a realistic metamaterial design to show that the
      required bianisotropy can be readily obtained. 

PMID- 26296132
TI  - Hot-Electron Intraband Luminescence from Single Hot Spots in Noble-Metal
      Nanoparticle Films.
AB  - Disordered noble-metal nanoparticle films exhibit highly localized and stable
      nonlinear light emission from subdiffraction regions upon illumination by near
      infrared femtosecond pulses. Such hot spot emission spans a continuum in the
      visible and near-infrared spectral range. Strong plasmonic enhancement of light
      matter interaction and the resulting complexity of experimental observations have
      prevented the development of a universal understanding of the origin of light
      emission. Here, we study the dependence of emission spectra on excitation
      irradiance and provide the most direct evidence yet that the continuum emission
      observed from both silver and gold nanoparticle aggregate surfaces is caused by
      recombination of hot electrons within the conduction band. The electron gas in
      the emitting particles, which is effectively decoupled from the lattice
      temperature for the duration of emission, reaches temperatures of several
      thousand Kelvin and acts as a subdiffraction incandescent light source on
      subpicosecond time scales. 

PMID- 26296133
TI  - Comment on "Asymptotic Phase for Stochastic Oscillators".

PMID- 26296134
TI  - Thomas and Lindner Reply.

PMID- 26296135
TI  - Shame among people living with HIV: a literature review.
AB  - Shame is consistently associated with poor adjustment (e.g., depressive symptoms)
      among community samples but, surprisingly, has rarely been directly examined
      among people living with HIV/AIDS (PLWH). This limited research on shame is
      likely due, in part, to shame's having been subsumed within measures of
      internalized stigma, an imprecise construct with varied definitions in the HIV
      literature. The current review summarizes research directly examining the
      correlates of shame among PLWH. Findings indicate that shame is associated with
      greater depressive symptoms, less healthcare utilization, and poorer physical
      health among PLWH. Directions for future research examining shame among PLWH are
      highlighted, including the need for more prospective research examining shame as
      a predictor of future adjustment. 

PMID- 26296137
TI  - Iron-Catalyzed Convergent Radical Cyclization of Aldehydes with Two Alkenes to
      3,4-Dihydropyrans.
AB  - A novel convergent radical cyclization of an aldehyde with two alkenes has been
      developed. With this method, polyfunctionalized 3,4-dihydropyrans are built in an
      efficient and selective manner. The iron-catalyzed redox radical recombinations
      are proposed for the formation of a 3,4-dihydropyran skeleton. 

PMID- 26296136
TI  - Sentinel Lymph Node Detection Using Carbon Nanoparticles in Patients with Early
      Breast Cancer.
AB  - PURPOSE: Carbon nanoparticles have a strong affinity for the lymphatic system.
      The purpose of this study was to evaluate the feasibility of sentinel lymph node
      biopsy using carbon nanoparticles in early breast cancer and to optimize the
      application procedure. METHODS: Firstly, we performed a pilot study to
      demonstrate the optimized condition using carbon nanoparticles for sentinel lymph
      nodes (SLNs) detection by investigating 36 clinically node negative breast cancer
      patients. In subsequent prospective study, 83 patients with clinically node
      negative breast cancer were included to evaluate SLNs using carbon nanoparticles.
      Another 83 SLNs were detected by using blue dye. SLNs detection parameters were
      compared between the methods. All patients irrespective of the SLNs status
      underwent axillary lymph node dissection for verification of axillary node status
      after the SLN biopsy. RESULTS: In pilot study, a 1 ml carbon nanoparticles
      suspension used 10-15min before surgery was associated with the best detection
      rate. In subsequent prospective study, with carbon nanoparticles, the
      identification rate, accuracy, false negative rate was 100%, 96.4%, 11.1%,
      respectively. The identification rate and accuracy were 88% and 95.5% with 15.8%
      of false negative rate using blue dye technique. The use of carbon nanoparticles
      suspension showed significantly superior results in identification rate (p =
      0.001) and reduced false-negative results compared with blue dye technique.
      CONCLUSION: Our study demonstrated feasibility and accuracy of using carbon
      nanoparticles for SLNs mapping in breast cancer patients. Carbon nanoparticles
      are useful in SLNs detection in institutions without access to radioisotope.

PMID- 26296138
TI  - Welcoming Diversity? Symbolic Boundaries and the Politics of Normativity in
      Kansas City's LGBTQ Communities.
AB  - Using document analysis and ethnographic field work, this article examines the
      debate within the LGBTQ community of Kansas City over the decision to hold its
      Pride festival in the Power and Light District (P&L), a renewed downtown area
      with a controversial dress code. Despite the developers' and city's goals of
      creating a cosmopolitan urban space that welcomed diverse populations, the P&L
      acquired a reputation as an anti-Black, anti-queer space due to its dress code
      and redevelopment history. I argue that the debate surrounding this controversy
      reveals limits to notions of diversity and diverging approaches to sexual
      politics within the LGBTQ community that are normally obscured by political
      actors within the movement but that work to create symbolic boundaries that
      exclude "non-respectable" members of the LGBTQ population. Recovering queer
      perspectives allows us to imagine a more capacious definition of diversity and
      inclusion, both within the LGBTQ movement and in urban space. 

PMID- 26296139
TI  - "Chimera" fully covered self-expandable metal stent for refractory esophageal
      anastomotic leak.

PMID- 26296140
TI  - Side-entry laser-beam zigzag irradiation of multiple channels in a microchip for
      simultaneous and highly sensitive detection of fluorescent analytes.
AB  - A simple and highly sensitive technique for laser-induced fluorescence detection
      on multiple channels in a plastic microchip was developed, and its effectiveness
      was demonstrated by laser-beam ray-trace simulations and experiments. In the
      microchip, with refractive index nC, A channels and B channels are arrayed
      alternately and respectively filled with materials with refractive indexes nA for
      electrophoresis analysis and nB for laser-beam control. It was shown that a laser
      beam entering from the side of the channel array traveled straight and irradiated
      all A channels simultaneously and effectively because the refractive actions by
      the A and B channels were counterbalanced according to the condition nA < nC <
      nB. This technique is thus called "side-entry laser-beam zigzag irradiation". As
      a demonstration of the technique, when nC = 1.53, nA = 1.41, nB = 1.66, and the
      cross sections of both eight A channels and seven B channels were the same
      isosceles trapezoids with 97 degrees  base angle, laser-beam irradiation
      efficiency on the eight A channels by the simulations was 89% on average and
      coefficient of variation was 4.4%. These results are far superior to those
      achieved by other conventional methods such as laser-beam expansion and scanning.
      Furthermore, fluorescence intensity on the eight A channels determined by the
      experiments agreed well with that determined by the simulations. Therefore,
      highly sensitive and uniform fluorescence detection on eight A channels was
      achieved. It is also possible to fabricate the microchips at low cost by plastic
      injection molding and to make a simple and compact detection system, thereby
      promoting actual use of the proposed side-entry laser-beam zigzag irradiation in
      various fields. 

PMID- 26296141
TI  - CT-based attenuation and scatter correction compared with uniform attenuation
      correction in brain perfusion SPECT imaging for dementia.
AB  - This study investigated if the appearance and diagnostic accuracy of HMPAO brain
      perfusion SPECT images could be improved by using CT-based attenuation and
      scatter correction compared with the uniform attenuation correction method. A
      cohort of subjects who were clinically categorized as Alzheimer's Disease (n =
      38), Dementia with Lewy Bodies (n = 29) or healthy normal controls (n = 30),
      underwent SPECT imaging with Tc-99m HMPAO and a separate CT scan. The SPECT
      images were processed using: (a) correction map derived from the subject's CT
      scan or (b) the Chang uniform approximation for correction or (c) no attenuation
      correction. Images were visually inspected. The ratios between key regions of
      interest known to be affected or spared in each condition were calculated for
      each correction method, and the differences between these ratios were evaluated.
      The images produced using the different corrections were noted to be visually
      different. However, ROI analysis found similar statistically significant
      differences between control and dementia groups and between AD and DLB groups
      regardless of the correction map used.We did not identify an improvement in
      diagnostic accuracy in images which were corrected using CT-based attenuation and
      scatter correction, compared with those corrected using a uniform correction map.

PMID- 26296143
TI  - Analyzing Neutrophil Morphology, Mechanics, and Motility in Sepsis: Options and
      Challenges for Novel Bedside Technologies.
AB  - OBJECTIVE: Alterations in neutrophil morphology (size, shape, and composition),
      mechanics (deformability), and motility (chemotaxis and migration) have been
      observed during sepsis. We combine summarizing features of neutrophil morphology,
      mechanics, and motility that change during sepsis with an investigation into
      their clinical utility as markers for sepsis through measurement with novel
      technologies. DATA SOURCES: We performed an initial literature search in MEDLINE
      using search terms "neutrophil," "morphology," "mechanics," "dynamics,"
      "motility," "mobility," "spreading," "polarization," "migration," and
      "chemotaxis." We then combined the results with "sepsis" and "septic shock." We
      scanned bibliographies of included articles to identify additional articles.
      STUDY SELECTION AND DATA EXTRACTION: Final selection was done after the authors
      reviewed recovered articles. We included articles based on their relevance for
      our review topic. DATA SYNTHESIS: When compared with resting conditions, sepsis
      causes an increase in circulating numbers of larger, more rigid neutrophils that
      show diminished granularity, migration, and chemotaxis. Combined measurement of
      these variables could provide a more complete view on neutrophil phenotype
      manifestation. For that purpose, sophisticated automated hematology analyzers,
      microscopy, and bedside microfluidic devices provide clinically feasible, high
      throughput, and cost-limiting means. CONCLUSIONS: We propose that integration of
      features of neutrophil morphology, mechanics, and motility with these new
      analytical methods can be useful as markers for diagnosis, prognosis, and
      monitoring of sepsis and may even contribute to basic understanding of its
      pathophysiology.

PMID- 26296142
TI  - Development of graphomotor fluency in adults with ADHD: Evidence of attenuated
      procedural learning.
AB  - PURPOSE: The present study sought to determine if adults with ADHD demonstrate
      reduced graphomotor learning relative to controls. METHOD: Twenty-eight control
      adults (n=14) and adults with ADHD (n=14) were recruited and wrote a novel
      grapheme on a digitizing tablet 30 times. Participants with ADHD were
      counterbalanced on and off stimulant medication. RESULTS: Control participants,
      F(1,13)=13.786, p=.003, omega(2)partial=.460, and participants with ADHD on
      medication, F(1,13)=10.462, p=.007, omega(2)partial=.387, demonstrated
      significant improvement in graphomotor fluency with equivalent practice whereas
      participants with ADHD off medication did not, F(1,12)=0.166, NS. CONCLUSIONS:
      Results indicate that graphomotor program learning in adults with ADHD may occur
      more slowly than typically developing peers. Findings have implications for
      providing accommodations to adults with ADHD, potential benefits of stimulant
      medication, and using digitizing technology as a neuropsychological assessment
      instrument.

PMID- 26296144
TI  - NODULAR POSTERIOR SCLERITIS: Clinico-Sonographic Characteristics and Proposed
      Diagnostic Criteria.
AB  - PURPOSE: To report the clinical and ultrasound features and outcomes of a series
      of nodular posterior scleritis. METHODS: Retrospective medical record review of
      11 consecutive patients with nodular posterior scleritis. Patient demographics,
      ocular and systemic findings, ultrasound features, and final anatomical and
      visual outcomes were recorded. RESULTS: There were 9 females and 2 males (11
      eyes) with mean age at presentation of 57 years (range, 30-84 years). Underlying
      systemic inflammatory disease was present in 73%. Symptoms included pain in 73%
      and blurred vision in 45%. A solitary amelanotic mass without the presence of
      lipofuscin was found in all cases. Associated ocular features included retinal
      pigment epithelial changes (67%), intraocular inflammation (55%), subretinal
      fluid (50%), macular edema (50%), and choroidal folds (30%). B-mode ultrasound
      showed a sclerochoroidal mass with high internal reflectivity (100%) of mean
      elevation of 4.1 mm. There was nodular thickening of the sclera (100%) and fluid
      in Tenon space or "T" sign (36%). A complete regression of the nodule after the
      treatment was observed only in 1 patient (11%) and partial regression in 4
      patients (44%). CONCLUSION: Nodular posterior scleritis should be considered in
      the differential diagnosis of a single amelanotic choroidal mass showing high
      internal reflectivity on ultrasound B-scan. It can produce intraocular
      inflammation in 50% of the cases and may be painless in 25%. It has a high
      association with a systemic underlying disease.

PMID- 26296145
TI  - GANGLION CELL LAYER THICKNESS AND VISUAL IMPROVEMENT AFTER EPIRETINAL MEMBRANE
      SURGERY.
AB  - PURPOSE: To evaluate the possible prognostic value of preoperative individual
      retinal layer thicknesses measured by an automated algorithm from spectral domain
      optical coherence tomography and visual acuity or improvement after epiretinal
      membrane surgery. METHODS: Data from 76 eyes with idiopathic epiretinal membrane
      that underwent pars plana vitrectomy for idiopathic epiretinal membrane removal
      were analyzed. The preoperative thicknesses of the ganglion cell layer, inner
      plexiform layer, and other layers were measured using the Iowa Reference
      Algorithm. Each retinal layer thickness and its ratio of the central foveal
      thickness were compared between eyes with (Group 1) or without (Group 2) 2 or
      more Snellen lines of visual improvement at 3, 6, and 12 months after surgery.
      RESULTS: Higher mean central foveal thickness/ganglion cell layer ratio and
      symptom duration of <=1 year were significantly more common in Group 1 (P = 0.03
      and 0.04, respectively). After adjusting for age and symptom duration, lens
      status, and preoperative visual acuity, higher central foveal thickness/ganglion
      cell layer ratio was associated with >=2 lines of visual improvement after
      surgery (odds ratio: 6.57, 95% confidence interval: 1.29-33.40). CONCLUSION: The
      preoperative inner retinal layer changes may have a role independent of outer
      retinal layer parameters in the visual prognosis after epiretinal membrane
      peeling.

PMID- 26296146
TI  - PREVALENCE OF THE COMPLEMENT FACTOR H AND GSTM1 GENES POLYMORPHISMS IN PATIENTS
      WITH CENTRAL SEROUS CHORIORETINOPATHY.
AB  - PURPOSE: The purpose of our study was to investigate the potential association
      between the complement factor H (CFH) (rs3753394, rs800292, rs2284664, rs1329428,
      and rs1065489) and GSTM1 gene polymorphisms, and central serous chorioretinopathy
      (CSCR) susceptibility in a well-defined Greek cohort. METHODS: We enrolled a case
      control study in a Greek population with 41 cases and 78 controls. Five
      milliliters of peripheral blood was collected from each participant, and DNA was
      extracted using the PureLink Genomic DNA kit. The CFH (rs3753394, rs800292,
      rs2284664, rs1329428, and rs1065489) single nucleotide polymorphisms and GSTM1
      polymorphism were tested using polymerase chain reaction assays. RESULTS: Between
      CSCR (n = 41) cases and controls (n = 78), the TT rs3753394, GG rs1329428, and TT
      rs1065489 genotypes' frequencies of the CFH gene were found to be significantly
      associated with risk of CSCR. The genotype frequency of the CFH rs2284664,
      rs800292, and of the GSTM1 gene polymorphisms was not found to be significantly
      associated with CSCR. CONCLUSION: Our results demonstrated a significant
      association between CSCR and single nucleotide polymorphisms in the CFH gene
      (rs3753394, rs1329428, and rs1065489), suggesting that disturbances in choroidal
      vasculature, through intercorrelation with adrenomedullin, play a significant
      role in CSCR pathogenesis.

PMID- 26296147
TI  - Initial Experience With Gallium-68 DOTA-Octreotate PET/CT and Peptide Receptor
      Radionuclide Therapy for Pediatric Patients With Refractory Metastatic
      Neuroblastoma.
AB  - RATIONALE: Pediatric patients with refractory neuroblastoma have limited
      therapeutic options. Neuroblastoma may express somatostatin receptors (SSTRs)
      allowing imaging with 68Ga-DOTA-Octreotate (GaTATE) positron emission
      tomography/computed tomography (PET/CT) and peptide receptor radionuclide therapy
      (PRRT). We reviewed our experience with this theranostic combination. MATERIALS
      AND METHODS: GaTATE studies (8 patients; 2 to 9 years old) were reviewed and
      compared with 123I-MIBG or posttreatment 131I-MIBG studies. Immunohistochemistry
      (IHC) for SSTR subtype 2 was performed in 5 patients. Four patients received
      PRRT. RESULTS: GaTATE PET showed additional disease in 38% (3/8 patients), and
      upstaged 1 patient by detecting marrow involvement. IHC detected SSTR 2 in all
      patients assessed. Six patients were deemed suitable for PRRT on imaging. Four
      patients received 17 cycles of palliative PRRT (10 111In-DOTATATE; 5 177Lu
      DOTATATE; 1 combined 111In and 177Lu-DOTATATE; 1 combined 177Lu and 90Y-DOTATATE)
      with no significant toxicity attributed to PRRT. All had objective responses. Two
      survivors are now 40 and 56 months from PRRT commencement. CONCLUSIONS: GaTATE
      PET was positive in a high proportion of patients with refractory neuroblastoma,
      correlating with SSTR 2 on IHC, with additional disease identified compared with
      MIBG imaging. PRRT seems safe, feasible, with responses observed in patients with
      progression despite multimodality treatment. These data support ongoing clinical
      trials in such patients.

PMID- 26296148
TI  - Synthesis of Spiroligomer-Containing Macrocycles.
AB  - We demonstrate the synthesis and characterization of the solution conformations
      of a collection of functionalized spiroligomer-based macrocycles. These
      macrocycles contain 14 independently controllable stereocenters and four
      independently controllable functional groups on a highly preorganized scaffold.
      These molecules are being developed to display complex, preorganized surfaces for
      binding proteins and to create enzyme-like active sites. In this work, we
      demonstrate the convergent synthetic approach to this new class of macrocycles
      and demonstrate that the conformational properties of these molecules can be
      changed by altering the configuration stereocenters within the backbone. 

PMID- 26296149
TI  - Assessment of physical activity of the human body considering the thermodynamic
      system.
AB  - Correctly dosed physical activity is the basis of a vital and healthy life, but
      the measurement of physical activity is certainly rather empirical resulting in
      limited individual and custom activity recommendations. Certainly, very accurate
      three-dimensional models of the cardiovascular system exist, however, requiring
      the numeric solution of the Navier-Stokes equations of the flow in blood vessels.
      These models are suitable for the research of cardiac diseases, but
      computationally very expensive. Direct measurements are expensive and often not
      applicable outside laboratories. This paper offers a new approach to assess
      physical activity using thermodynamical systems and its leading quantity of
      entropy production which is a compromise between computation time and precise
      prediction of pressure, volume, and flow variables in blood vessels. Based on a
      simplified (one-dimensional) model of the cardiovascular system of the human
      body, we develop and evaluate a setup calculating entropy production of the heart
      to determine the intensity of human physical activity in a more precise way than
      previous parameters, e.g. frequently used energy considerations. The knowledge
      resulting from the precise real-time physical activity provides the basis for an
      intelligent human-technology interaction allowing to steadily adjust the degree
      of physical activity according to the actual individual performance level and
      thus to improve training and activity recommendations. 

PMID- 26296150
TI  - Reawakening the sleeping beauty in the adult brain: neurogenesis from parenchymal
      glia.
AB  - Life-long neurogenesis is highly restricted to specialized niches in the adult
      mammalian brain and therefore the brain's capacity for spontaneous regeneration
      is extremely limited. However, recent work has demonstrated that under certain
      circumstances parenchymal astrocytes and NG2 glia can generate neuronal progeny.
      In the striatum, stroke or excitotoxic lesions can reawaken in astrocytes a
      latent neurogenic program resulting in the genesis of new neurons. By contrast,
      in brain areas that fail to mount a neurogenic response following injury, such as
      the cerebral cortex, forced expression of neurogenic reprogramming factors can
      lineage convert local glia into induced neurons. Yet, injury-induced and
      reprogramming-induced neurogenesis exhibit intriguing commonalities, suggesting
      that they may converge on similar mechanisms. 

PMID- 26296151
TI  - Di-tert-butyl peroxide-mediated atom-transfer radical addition of 2
      chlorodithiane to aryl alkynes under mild conditions.
AB  - Atom transfer radical addition (ATRA) of 2-chlorodithiane onto aryl alkynes
      through the use of di-tert-butyl peroxide as an oxidant at room temperature
      directly affords a variety of synthetically valuable beta-chloro-(Z)-vinyl
      dithianes in good yields with high regioselectivities and without the assistance
      of any transition metals. It provides an operationally simple pathway to access
      vinyl dithianes with controlled formation of a new C(sp(2) )?C bond and a C(sp(2)
      )?Cl bond. 

PMID- 26296152
TI  - Liver Perilipin 5 Expression Worsens Hepatosteatosis But Not Insulin Resistance
      in High Fat-Fed Mice.
AB  - Perilipin 5 (PLIN5) is a lipid droplet (LD) protein highly expressed in oxidative
      tissues, including the fasted liver. However, its expression also increases in
      nonalcoholic fatty liver. To determine whether PLIN5 regulates metabolic
      phenotypes of hepatosteatosis under nutritional excess, liver targeted
      overexpression of PLIN5 was achieved using adenoviral vector (Ad-PLIN5) in male
      C57BL/6J mice fed high-fat diet. Mice treated with adenovirus expressing green
      fluorescent protein (GFP) (Ad-GFP) served as control. Ad-PLIN5 livers increased
      LD in the liver section, and liquid chromatography with tandem mass spectrometry
      revealed increases in lipid classes associated with LD, including
      triacylglycerol, cholesterol ester, and phospholipid classes, compared with Ad
      GFP liver. Lipids commonly associated with hepatic lipotoxicity, diacylglycerol,
      and ceramides, were also increased in Ad-PLIN5 liver. The expression of genes in
      lipid metabolism regulated by peroxisome proliferator-activated receptor-alpha
      was reduced suggestive of slower mobilization of stored lipids in Ad-PLIN5 mice.
      However, the increase of hepatosteatosis by PLIN5 overexpression did not worsen
      glucose homeostasis. Rather, serum insulin levels were decreased, indicating
      better insulin sensitivity in Ad-PLIN5 mice. Moreover, genes associated with
      liver injury were unaltered in Ad-PLIN5 steatotic liver compared with Ad-GFP
      control. Phosphorylation of protein kinase B was increased in Ad-PLIN5-transduced
      AML12 hepatocyte despite of the promotion of fatty acid incorporation to
      triacylglycerol as well. Collectively, our data indicates that the increase in
      liver PLIN5 during hepatosteatosis drives further lipid accumulation but does not
      adversely affect hepatic health or insulin sensitivity. 

PMID- 26296153
TI  - ISL1 Is Necessary for Maximal Thyrotrope Response to Hypothyroidism.
AB  - ISLET1 is a homeodomain transcription factor necessary for development of the
      pituitary, retina, motor neurons, heart, and pancreas. Isl1-deficient mice (Isl1(
      /-)) die early during embryogenesis at embryonic day 10.5 due to heart defects,
      and at that time, they have an undersized pituitary primordium. ISL1 is expressed
      in differentiating pituitary cells in early embryogenesis. Here, we report the
      cell-specific expression of ISL1 and assessment of its role in gonadotropes and
      thyrotropes. Isl1 expression is elevated in pituitaries of Cga(-/-) mice, a model
      of hypothyroidism with thyrotrope hypertrophy and hyperplasia. Thyrotrope
      specific disruption of Isl1 with Tshb-cre is permissive for normal serum TSH, but
      T4 levels are decreased, suggesting decreased thyrotrope function. Inducing
      hypothyroidism in normal mice causes a reduction in T4 levels and dramatically
      elevated TSH response, but mice with thyrotrope-specific disruption of Isl1 have
      a blunted TSH response. In contrast, deletion of Isl1 in gonadotropes with an Lhb
      cre transgene has no obvious effect on gonadotrope function or fertility. These
      results show that ISL1 is necessary for maximal thyrotrope response to
      hypothyroidism, in addition to its role in development of Rathke's pouch. 

PMID- 26296155
TI  - A Bayesian approach to distinguishing interdigitated tongue muscles from limited
      diffusion magnetic resonance imaging.
AB  - The tongue is a critical organ for a variety of functions, including swallowing,
      respiration, and speech. It contains intrinsic and extrinsic muscles that play an
      important role in changing its shape and position. Diffusion tensor imaging (DTI)
      has been used to reconstruct tongue muscle fiber tracts. However, previous
      studies have been unable to reconstruct the crossing fibers that occur where the
      tongue muscles interdigitate, which is a large percentage of the tongue volume.
      To resolve crossing fibers, multi-tensor models on DTI and more advanced imaging
      modalities, such as high angular resolution diffusion imaging (HARDI) and
      diffusion spectrum imaging (DSI), have been proposed. However, because of the
      involuntary nature of swallowing, there is insufficient time to acquire a
      sufficient number of diffusion gradient directions to resolve crossing fibers
      while the in vivo tongue is in a fixed position. In this work, we address the
      challenge of distinguishing interdigitated tongue muscles from limited diffusion
      magnetic resonance imaging by using a multi-tensor model with a fixed tensor
      basis and incorporating prior directional knowledge. The prior directional
      knowledge provides information on likely fiber directions at each voxel, and is
      computed with anatomical knowledge of tongue muscles. The fiber directions are
      estimated within a maximum a posteriori (MAP) framework, and the resulting
      objective function is solved using a noise-aware weighted l1-norm minimization
      algorithm. Experiments were performed on a digital crossing phantom and in vivo
      tongue diffusion data including three control subjects and four patients with
      glossectomies. On the digital phantom, effects of parameters, noise, and prior
      direction accuracy were studied, and parameter settings for real data were
      determined. The results on the in vivo data demonstrate that the proposed method
      is able to resolve interdigitated tongue muscles with limited gradient
      directions. The distributions of the computed fiber directions in both the
      controls and the patients were also compared, suggesting a potential clinical use
      for this imaging and image analysis methodology. 

PMID- 26296154
TI  - Retinoic Acid Signaling Regulates Differential Expression of the Tandemly
      Duplicated Long Wavelength-Sensitive Cone Opsin Genes in Zebrafish.
AB  - The signaling molecule retinoic acid (RA) regulates rod and cone photoreceptor
      fate, differentiation, and survival. Here we elucidate the role of RA in
      differential regulation of the tandemly-duplicated long wavelength-sensitive
      (LWS) cone opsin genes. Zebrafish embryos were treated with RA from 48 hours post
      fertilization (hpf) to 75 hpf, and RNA was isolated from eyes for microarray
      analysis. ~170 genes showed significantly altered expression, including several
      transcription factors and components of cellular signaling pathways. Of interest,
      the LWS1 opsin gene was strongly upregulated by RA. LWS1 is the upstream member
      of the tandemly duplicated LWS opsin array and is normally not expressed
      embryonically. Embryos treated with RA 48 hpf to 100 hpf or beyond showed
      significant reductions in LWS2-expressing cones in favor of LWS1-expressing
      cones. The LWS reporter line, LWS-PAC(H) provided evidence that individual LWS
      cones switched from LWS2 to LWS1 expression in response to RA. The RA signaling
      reporter line, RARE:YFP indicated that increased RA signaling in cones was
      associated with this opsin switch, and experimental reduction of RA signaling in
      larvae at the normal time of onset of LWS1 expression significantly inhibited
      LWS1 expression. A role for endogenous RA signaling in regulating differential
      expression of the LWS genes in postmitotic cones was further supported by the
      presence of an RA signaling domain in ventral retina of juvenile zebrafish that
      coincided with a ventral zone of LWS1 expression. This is the first evidence that
      an extracellular signal may regulate differential expression of opsin genes in a
      tandemly duplicated array. 

PMID- 26296157
TI  - A new frontier for an old drug? A word of caution for beta-blockers in sepsis!
AB  - Recent promising findings indicate a possible benefit of beta-blockade in septic
      patients. Ongoing trials on esmolol in septic shock are investigating its
      hemodynamic effects, focusing on heart rate control and echocardiographic
      changes, as well as potential anti-inflammatory effects. However, given the
      complex physiology of sepsis and pharmacological effects on beta-blockade, large
      multi-center trials are essential before such a therapy may be applied safely. 

PMID- 26296156
TI  - Texture analysis applied to second harmonic generation image data for ovarian
      cancer classification.
AB  - Remodeling of the extracellular matrix has been implicated in ovarian cancer. To
      quantitate the remodeling, we implement a form of texture analysis to delineate
      the collagen fibrillar morphology observed in second harmonic generation
      microscopy images of human normal and high grade malignant ovarian tissues. In
      the learning stage, a dictionary of "textons"-frequently occurring texture
      features that are identified by measuring the image response to a filter bank of
      various shapes, sizes, and orientations-is created. By calculating a
      representative model based on the texton distribution for each tissue type using
      a training set of respective second harmonic generation images, we then perform
      classification between images of normal and high grade malignant ovarian tissues.
      By optimizing the number of textons and nearest neighbors, we achieved
      classification accuracy up to 97% based on the area under receiver operating
      characteristic curves (true positives versus false positives). The local analysis
      algorithm is a more general method to probe rapidly changing fibrillar
      morphologies than global analyses such as FFT. It is also more versatile than
      other texture approaches as the filter bank can be highly tailored to specific
      applications (e.g., different disease states) by creating customized libraries
      based on common image features.

PMID- 26296158
TI  - Glyceollin Effects on MRP2 and BCRP in Caco-2 Cells, and Implications for
      Metabolic and Transport Interactions.
AB  - Glyceollins are phytoalexins produced in soybeans under stressful growth
      conditions. On the basis of prior evaluations, they show potential to treat
      multiple diseases, including certain cancers, Type 2 diabetes, and cardiovascular
      conditions. The aim of the present study was to expand on recent studies designed
      to initially characterize the intestinal disposition of glyceollins.
      Specifically, studies were undertaken in Caco-2 cells to evaluate glyceollins'
      effects on apical efflux transporters, namely, MRP2 and BCRP, which are the locus
      of several intestinal drug-drug and drug-food interactions. 5- (and 6)-carboxy
      2',7'-dichloroflourescein (CDF) was used to provide a readout on MRP2 activity,
      whereas BODIPY-prazosin provided an indication of BCRP alteration. Glyceollins
      were shown to reverse MRP2-mediated CDF transport asymmetry in a concentration
      dependent manner, with activity similar to the MRP2 inhibitor, MK-571. Likewise,
      they demonstrated concentration-dependent inhibition of BCRP-mediated efflux of
      BODIPY-prazosin with a potency similar to that of Ko143. Glyceollin did not
      appreciably alter MRP2 or BCRP expression following 24 h of continuous exposure.
      The possibility that glyceollin mediated inhibition of genistein metabolite
      efflux by either transporter was evaluated. However, results demonstrated an
      interaction at the level of glyceollin inhibition of genistein metabolism rather
      than inhibition of metabolite transport. 

PMID- 26296164
TI  - Radiative Exchange between Graphitic Nanostructures: A Microscopic Perspective.
AB  - Electromagnetic radiative heat exchange involving graphene nanostrucrures is
      studied using an atomistic approach based on the coupled dipole method modified
      by the fluctuation dissipation theorem. This method includes taking into account
      many-particle electromagnetic contributions and enables treating two or more
      nanostructures with nontrivial boundary conditions at different temperatures. We
      present a microscopic picture of the heat exchange process in graphene
      nanostructured based systems in terms of a transmission coefficient,
      characteristic temperature function, and atomic morphology. Our studies provide
      general pathways of near-field radiation control at the nanoscale. 

PMID- 26296165
TI  - Absolute Ultraviolet Absorption Spectrum of a Criegee Intermediate CH2OO.
AB  - We present the time-resolved UV absorption spectrum of the B ((1)A') <- X ((1)A')
      electronic transition of formaldehyde oxide, CH2OO, produced by the reaction of
      CH2I radicals with O2. In contrast to its UV photodissociation action spectrum,
      the absorption spectrum of formaldehyde oxide extends to longer wavelengths and
      exhibits resolved vibrational structure on its low-energy side. Chemical kinetics
      measurements of its reactivity establish the identity of the absorbing species as
      CH2OO. Separate measurements of the initial CH2I radical concentration allow a
      determination of the absolute absorption cross section of CH2OO, with the value
      at the peak of the absorption band, 355 nm, of sigmaabs = (3.6 +/- 0.9) * 10(-17)
      cm(2). The difference between the absorption and action spectra likely arises
      from excitation to long-lived B ((1)A') vibrational states that relax to lower
      electronic states by fluorescence or nonradiative processes, rather than by
      photodissociation. 

PMID- 26296162
TI  - DNA methylation pathways and their crosstalk with histone methylation.
AB  - Methylation of DNA and of histone 3 at Lys 9 (H3K9) are highly correlated with
      gene silencing in eukaryotes from fungi to humans. Both of these epigenetic marks
      need to be established at specific regions of the genome and then maintained at
      these sites through cell division. Protein structural domains that specifically
      recognize methylated DNA and methylated histones are key for targeting enzymes
      that catalyse these marks to appropriate genome sites. Genetic, genomic,
      structural and biochemical data reveal connections between these two epigenetic
      marks, and these domains mediate much of the crosstalk. 

PMID- 26296166
TI  - Toward Ab Initio Optical Spectroscopy of the Fenna-Matthews-Olson Complex.
AB  - We present progress toward a first-principles parametrization of the Hamiltonian
      of the Fenna-Matthews-Olson pigment-protein complex, a molecule that has become
      key to understanding the role of quantum dynamics in photosynthetic exciton
      energy transfer. To this end, we have performed fully quantum mechanical
      calculations on each of the seven bacteriochlorophyll pigments that make up the
      complex, including a significant proportion of their protein environment (more
      than 2000 atoms), using linear-scaling density functional theory exploiting a
      recent development for the computation of excited states. Local pigment
      transition energies and interpigment coupling between optical transitions have
      been calculated and are in good agreement with the literature consensus.
      Comparisons between simulated and experimental optical spectra point toward
      future work that may help to elucidate important design principles in these
      nanoscale devices. 

PMID- 26296167
TI  - Small Photocarrier Effective Masses Featuring Ambipolar Transport in
      Methylammonium Lead Iodide Perovskite: A Density Functional Analysis.
AB  - Methylammonium lead iodide perovskite (CH3NH3PbI3) plays an important role in
      light absorption and carrier transport in efficient organic-inorganic perovskite
      solar cells. In this Letter, we report the first theoretical estimation of
      effective masses of photocarriers in CH3NH3PbI3. Effective masses of
      photogenerated electrons and holes were estimated to be me* = 0.23m0 and mh* =
      0.29m0, respectively, including spin-orbit coupling effects. This result is
      consistent with the long-range ambipolar transport property and with the larger
      diffusion constant for electrons compared with that for holes in the perovskite,
      which enable efficient photovoltaic conversion. 

PMID- 26296163
TI  - Microfluidics: reframing biological enquiry.
AB  - The underlying physical properties of microfluidic tools have led to new
      biological insights through the development of microsystems that can manipulate,
      mimic and measure biology at a resolution that has not been possible with
      macroscale tools. Microsystems readily handle sub-microlitre volumes, precisely
      route predictable laminar fluid flows and match both perturbations and
      measurements to the length scales and timescales of biological systems. The
      advent of fabrication techniques that do not require highly specialized
      engineering facilities is fuelling the broad dissemination of microfluidic
      systems and their adaptation to specific biological questions. We describe how
      our understanding of molecular and cell biology is being and will continue to be
      advanced by precision microfluidic approaches and posit that microfluidic tools -
      in conjunction with advanced imaging, bioinformatics and molecular biology
      approaches - will transform biology into a precision science. 

PMID- 26296168
TI  - Rate-Dependent Morphology of Li2O2 Growth in Li-O2 Batteries.
AB  - Compact solid discharge products enable energy storage devices with high
      gravimetric and volumetric energy densities, but solid deposits on active
      surfaces can disturb charge transport and induce mechanical stress. In this
      Letter, we develop a nanoscale continuum model for the growth of Li2O2 crystals
      in lithium-oxygen batteries with organic electrolytes, based on a theory of
      electrochemical nonequilibrium thermodynamics originally applied to Li-ion
      batteries. As in the case of lithium insertion in phase-separating LiFePO4
      nanoparticles, the theory predicts a transition from complex to uniform
      morphologies of Li2O2 with increasing current. Discrete particle growth at low
      discharge rates becomes suppressed at high rates, resulting in a film of
      electronically insulating Li2O2 that limits cell performance. We predict that the
      transition between these surface growth modes occurs at current densities close
      to the exchange current density of the cathode reaction, consistent with
      experimental observations. 

PMID- 26296169
TI  - Energetics of Water Oxidation Catalyzed by Cobalt Oxide Nanoparticles: Assessing
      the Accuracy of DFT and DFT+U Approaches against Coupled Cluster Methods.
AB  - Some of the most promising catalysts for water oxidation rely on crystalline and
      amorphous cobalt oxide nanoparticles. Density functional theory (DFT)
      calculations are routinely used to study the electronic and atomic structures of
      these materials as well as the thermodynamics and mechanisms of the
      electrochemical oxygen evolution reaction. The accuracy of these theoretical
      predictions has never been compared to high-level quantum chemistry methods. We
      perform coupled cluster (CC) quantum chemistry calculations on model cobalt oxide
      surface sites and use them to benchmark the accuracy of the most popular exchange
      and correlation functionals. Hybrid B3LYP and PBE0 functionals lead to fair
      agreement with the CC energies, while standard gradient-corrected functionals
      show important discrepancies. The inclusion of on-site electronic repulsion
      (DFT+U) substantially improves the calculated electronic and structural
      properties, but no value of the U parameter reproduces the CC results. We discuss
      the implications of these findings for amorphous cobalt phosphate nanoparticles,
      showing that the reactivity of these catalysts is not altered by surface
      phosphate groups. 

PMID- 26296170
TI  - Surface Prevalence of Perchlorate Anions at the Air/Aqueous Interface.
AB  - Air/aqueous interfaces provide a unique environment for many chemical,
      environmental, and biological processes. To gain insight, molecular-level
      understanding of the interfacial water organization and ion distributions at
      these interfaces is required. Here, the air/aqueous interface of NaClO4 salt
      solutions was investigated by means of conventional and heterodyne-detected
      vibrational sum frequency generation (HD-VSFG) spectroscopy. It is found that
      perchlorate (ClO4(-)) ions exist in the interfacial region and prefer to reside
      on average above their counterions. This finding is inferred from the average
      orientation of the OH transition dipole moment of interfacial water molecules
      governed by the direction of the net electric field arising from the interfacial
      ion distributions. At the air/aqueous interface of NaClO4 salt solutions, the net
      dipole moments of hydrogen-bonded water molecules are oriented preferentially
      toward the vapor phase. Contrary to some other salts (e.g., sulfates), the
      presence of ClO4(-) may cause a full reversal in the direction of the interfacial
      electric field at a higher concentration (>=1.7 M). Another interpretation for
      the positive Im chi((2)) spectra of NaClO4 salt solutions could be an increase in
      the population of water species contributing positively to the net OH transition
      dipole moment. Regardless of the mechanism, this effect becomes even more
      pronounced with increasing salt concentration. 

PMID- 26296171
TI  - Roaming Dissociation of Ethyl Radicals.
AB  - Previous studies on the photodissociation of C2H5 reported rate constants for H
      atom formation several orders of magnitude smaller than that predicted by Rice
      Ramsperger-Kassel-Marcus (RRKM) theory. This Letter provides a potential
      explanation for this anomaly, based on direct trajectory calculations of C2H5
      dissociation. The trajectories reveal the existence of a roaming dissociation
      channel that leads to the formation of C2H3 and H2. This channel is found to
      proceed over the ridge between the transition state of H-atom elimination and
      that of bimolecular H-abstraction. The formed C2H3 radical can subsequently
      dissociate to C2H2 and a H atom; this secondary dissociation is suggested to be a
      potential reason for the unexpectedly slow H-atom formation observed in the
      photodissociation experiments. 

PMID- 26296172
TI  - Fast Crystallization of the Phase Change Compound GeTe by Large-Scale Molecular
      Dynamics Simulations.
AB  - Phase change materials are of great interest as active layers in rewritable
      optical disks and novel electronic nonvolatile memories. These applications rest
      on a fast and reversible transformation between the amorphous and crystalline
      phases upon heating, taking place on the nanosecond time scale. In this work, we
      investigate the microscopic origin of the fast crystallization process by means
      of large-scale molecular dynamics simulations of the phase change compound GeTe.
      To this end, we use an interatomic potential generated from a Neural Network
      fitting of a large database of ab initio energies. We demonstrate that in the
      temperature range of the programming protocols of the electronic memories (500
      700 K), nucleation of the crystal in the supercooled liquid is not rate-limiting.
      In this temperature range, the growth of supercritical nuclei is very fast
      because of a large atomic mobility, which is, in turn, the consequence of the
      high fragility of the supercooled liquid and the associated breakdown of the
      Stokes-Einstein relation between viscosity and diffusivity. 

PMID- 26296173
TI  - A Simple Theory for the Hofmeister Series.
AB  - In cells, biological molecules function in an aqueous solution. Electrolytes and
      other small molecules play important roles in keeping the osmotic pressure of the
      cellular environment as well as the structure formation and function of
      biomolecules. The observed empirical rules such as Hofmeister series are still
      waiting for molecular interpretations. In this Perspective, we will discuss a
      simple and self-consistent theory that takes into account the cooperative effects
      of cations and anions in affecting water/air surface tension, water activity, and
      the solubility of model compounds including polypeptides. Molecular dynamics
      simulations used to test these theoretical models will also be discussed. 

PMID- 26296174
TI  - Charge Generation Dynamics in CdS:P3HT Blends for Hybrid Solar Cells.
AB  - Development of design rules for hybrid inorganic-organic solar cells through
      understanding charge generation and recombination dynamics is an important
      pathway for the improvement of solar cell conversion efficiencies. In this
      Letter, we study the dynamics of charge generation in CdS:polymer blends by
      transient absorption spectroscopy. We show that charge generation following
      excitation of the inorganic component is highly efficient and can occur up to a
      few nanoseconds after excitation, allowing for diffusion of charges within the
      inorganic component to an interface. In contrast, charge generation following
      excitation of the organic component occurs on subpicosecond time scales but
      suffers from two loss processes, incomplete exciton dissociation and geminate
      recombination. 

PMID- 26296175
TI  - Hofmeister Series of Ions: A Simple Theory of a Not So Simple Reality.

PMID- 26296176
TI  - Selective Excitation of Atomic-Scale Dynamics by Coherent Exciton Motion in the
      Non-Born-Oppenheimer Regime.
AB  - Time-domain investigations of the nonadiabatic coupling between electronic and
      vibrational degrees of freedom have focused primarily on the formation of
      electronic superpositions induced by atomic motion. The effect of electronic
      nonstationary-state dynamics on atomic motion remains unexplored. Here, phase
      coherent excitation of the two lowest electronic transitions in semiconducting
      single-walled carbon nanotubes by broadband <5-fs pulses directly triggers
      coherent exciton motion along the axis of the nanotubes. Optical pump-probe
      spectroscopy with sub-10-fs time resolution reveals that exciton motion
      selectively excites the high-frequency G mode coherent phonon, in good agreement
      with results obtained from time-domain ab initio simulations. This observed
      phenomenon arises from the direct modulation of the C-C interatomic potential by
      coherent exciton motion on a time scale that is commensurate with atomic motion.
      Our results suggest the possibility of employing light-field manipulation of
      electron densities in the non-Born-Oppenheimer regime to initiate selective
      atomic motion. 

PMID- 26296177
TI  - Size-Dependent Surface Free Energy and Tolman-Corrected Droplet Nucleation of
      TIP4P/2005 Water.
AB  - Classical nucleation theory is notoriously inaccurate when using the macroscopic
      surface free energy for a planar interface. We examine the size dependence of the
      surface free energy for TIP4P/2005 water nanodroplets (radii ranging from 0.7 to
      1.6 nm) at 300 K with the mitosis method, that is, by reversibly splitting the
      droplets into two subclusters. We calculate the Tolman length to be -0.56 +/-
      0.09 A, which indicates that the surface free energy of water droplets that we
      investigated is 5-11 mJ/m(2) greater than the planar surface free energy. We
      incorporate the computed Tolman length into a modified classical nucleation
      theory (delta-CNT) and obtain modified expressions for the critical nucleus size
      and barrier height. delta-CNT leads to excellent agreement with independently
      measured nucleation kinetics. 

PMID- 26296178
TI  - Spatially Heterogeneous Dynamics in the Density Scaling Regime: Time and Length
      Scales of Molecular Dynamics near the Glass Transition.

PMID- 26296179
TI  - The Mechanochemistry of a Structural Zinc Finger.
AB  - Zinc fingers are highly ubiquitous structural motifs that provide stability to
      proteins, thus contributing to their correct folding. Despite the high
      thermodynamic stability of the ZnCys4 centers, their kinetic properties display
      remarkable lability. Here, we use a combination of protein engineering with
      single molecule force spectroscopy atomic force microscopy (AFM) to uncover the
      surprising mechanical lability (~90 pN) of the individual Zn-S bonds that form
      the two equivalent zinc finger motifs embedded in the structure of the
      multidomain DnaJ chaperone. Rational mutations within the zinc coordinating
      residues enable direct identification of the chemical determinants that regulate
      the interplay between zinc binding-requiring the presence of all four cysteines
      and disulfide bond formation. Finally, our observations show that binding to
      hydrophobic short peptides drastically increases the mechanical stability of
      DnaJ. Altogether, our experimental approach offers a detailed, atomistic vista on
      the fine chemical mechanisms that govern the nanomechanics of individual,
      naturally occurring zinc finger. 

PMID- 26296181
TI  - Stimuli-responsive DNA-functionalized nano-/microcontainers for switchable and
      controlled release.
AB  - Stimuli-responsive DNA-functionalized nano- and microcontainers composed of
      mesoporous SiO2 nanoparticles (MP SiO2 NPs), microcapsules, or micelles/vesicles
      act as carriers for the transport and release of drugs. The information encoded
      in the DNA sequences provides instructive information for the gating of drug
      loaded pores of MP SiO2 NPs, for the assembly and degradation of microcapsules or
      lipid-DNA micelles/vesicles, and for the targeting of nano-/microcontainers to
      cancer cells. Different triggers are applied to release the drugs loaded in the
      nano-/microcontainers by unlocking the pores of the MP SiO2 NPs or by degradation
      of the containers. These include the use of switchable DNA nanostructures
      (nucleic acid hairpins, i-motif, G-quadruplexes) and the implementation of
      chemical, thermal, or photonic stimuli. Also, catalytic processes stimulated by
      DNAzymes or enzymes are used to release drugs from the nano-/microcontainers. 

PMID- 26296180
TI  - Levels of nutrients in relation to fish consumption among older male anglers in
      Wisconsin.
AB  - Fish is an important source of nutrients including omega-3 fatty acids, which may
      reduce risk of adverse health outcomes such as cardiovascular disease; however,
      fish may also contain significant amounts of environmental pollutants. The
      Wisconsin Departments of Health Services and Natural Resources developed a survey
      instrument, along with a strategy to collect human biological samples to assess
      the risks and benefits associated with long-term fish consumption among older
      male anglers in Wisconsin. The target population was men aged 50 years and older,
      who fish Wisconsin waters and live in the state of Wisconsin. Participants
      provided blood and hair samples and completed a detailed (paper) questionnaire,
      which included questions on basic demographics, health status, location of catch
      and species of fish caught/eaten, consumption of locally caught and commercially
      purchased fish, and awareness and source of information for local and statewide
      consumption guidelines. Biological samples were used to assess levels of
      docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), eicosapentaenoic acid
      (EPA); vitamin D; and selenium in blood. Quantile regression analysis was used to
      investigate the associations between biomarker levels and self-reported
      consumption of fish from the Great Lakes and other areas of concern, other
      locally caught fish, and commercially purchased fish (meals per year).
      Respondents were largely non-Hispanic white men in their 60's with at least some
      college education, and about half were retired. Fish consumption was high (median
      of 54.5 meals per year), with most fish meals coming from locally-caught fish.
      Multivariate regression models showed that the effect of supplement use was much
      greater than that of fish consumption, on nutrient levels, although consumption
      of fish from the Great Lakes and areas of concern was significantly associated
      with higher levels of vitamin D even after controlling for supplement usage. 

PMID- 26296184
TI  - Environmental Mutagenesis and Genomics Society 46th Annual Meeting.

PMID- 26296182
TI  - Exposure measurement in bicycle safety analysis: A review of the literature.
AB  - BACKGROUND: Cycling, as an active mode of transportation, has well-established
      health benefits. However, the safety of cyclists in traffic remains a major
      concern. In-depth studies of potential risk factors and safety outcomes are
      needed to ensure the most appropriate actions are taken to improve safety.
      However, the lack of reliable exposure data hinders meaningful analysis and
      interpretation. In this paper, we review the bicycle safety literature reporting
      different methods for measuring cycling exposure and discuss their findings.
      METHODS: A literature search identified studies on bicycle safety that included a
      description of how cycling exposure was measured, and what exposure units were
      used (e.g. distance, time, trips). Results were analyzed based on whether
      retrospective or prospective measurement of exposure was used, and whether safety
      outcomes controlled for exposure. RESULTS: We analyzed 20 papers. Retrospective
      studies were dominated by major bicycle accidents, whereas the prospective
      studies included minor and major bicycle accidents. Retrospective studies
      indicated higher incidence rates (IR) of accidents for men compared to women, and
      an increased risk of injury for cyclists aged 50 years or older. There was a lack
      of data for cyclists younger than 18 years. The risk of cycling accidents
      increased when riding in the dark. Wearing visible clothing or a helmet, or
      having more cycling experience did not reduce the risk of being involved in an
      accident. Better cyclist-driver awareness and more interaction between car driver
      and cyclists, and well maintained bicycle-specific infrastructure should improve
      bicycle safety. CONCLUSION: The need to include exposure in bicycle safety
      research is increasingly recognized, but good exposure data are often lacking,
      which makes results hard to interpret and compare. Studies including exposure
      often use a retrospective research design, without including data on minor
      bicycle accidents, making it difficult to compare safety levels between age
      categories or against different types of infrastructure. Future research should
      focus more on children and adolescents, as this age group is a vulnerable
      population and is underrepresented in the existing literature.

PMID- 26296185
TI  - Long-term storage and preservation of tissue engineered articular cartilage.
AB  - With limited availability of osteochondral allografts, tissue engineered
      cartilage grafts may provide an alternative treatment for large cartilage
      defects. An effective storage protocol will be critical for translating this
      technology to clinical use. The purpose of this study was to evaluate the
      efficacy of the Missouri Osteochondral Allograft Preservation System (MOPS) for
      room temperature storage of mature tissue engineered grafts, focusing on tissue
      property maintenance during the current allograft storage window (28 days).
      Additional research compares MOPS to continued culture, investigates temperature
      influence, and examines longer-term storage. Articular cartilage constructs were
      cultured to maturity using adult canine chondrocytes, then preserved with MOPS at
      room temperature, in refrigeration, or kept in culture for an additional 56 days.
      MOPS storage maintained desired chondrocyte viability for 28 days of room
      temperature storage, retaining 75% of the maturity point Young's modulus without
      significant decline in biochemical content. Properties dropped past this time
      point. Refrigeration maintained properties similar to room temperature at 28
      days, but proved better at 56 days. For engineered grafts, MOPS maintained the
      majority of tissue properties for the 28-day window without clearly extending
      that period as it had for native grafts. These results are the first evaluating
      engineered cartilage storage.

PMID- 26296187
TI  - Pazopanib in ovarian cancer.
AB  - The majority of women with ovarian cancer present with advanced disease, and
      ultimately relapse following primary surgery and platinum-taxane chemotherapy.
      Despite recent advances in the development of targeted agents in ovarian cancer,
      survival rates remain poor. The promising activity of bevacizumab, a VEGF
      receptor inhibitor, has stimulated research on the use of additional anti
      angiogenic agents in ovarian cancer. Pazopanib, an oral tyrosine kinase
      inhibitor, targets VEGF receptor-1, -2 and -3, platelet-derived growth factor
      receptor-alpha and -beta and c-kit; resulting in the inhibition of angiogenesis
      and tumor proliferation. Early phase studies have demonstrated promising efficacy
      and tolerability. To date, there has been one Phase III trial of pazopanib in
      ovarian cancer, demonstrating a progression-free survival benefit in women
      treated with maintenance pazopanib following primary surgery and systemic
      therapy. This article summarizes the preclinical and clinical data of pazopanib
      in ovarian cancer, highlighting future research options for this agent. 

PMID- 26296186
TI  - Menstrual Needs and Associations with Sexual and Reproductive Risks in Rural
      Kenyan Females: A Cross-Sectional Behavioral Survey Linked with HIV Prevalence.
AB  - BACKGROUND: Females in low and middle income countries (LMICs) have difficulty
      coping with menstrual needs, but few studies have examined the social or health
      implications of these needs. METHODS: Responses from 3418 menstruating females
      aged 13-29 years were extracted from an HIV and behavioral risks cross-sectional
      survey conducted in rural western Kenya. We examined sanitary products used,
      provision of products from sexual partners or from transactional sex, and
      demographic and sexual exposures. RESULTS: Overall, 75% of females reported using
      commercial pads and 25% used traditional materials such as cloth or items like
      paper or tissue, with 10% of girls <15 years old depending on makeshift items.
      Two-thirds of females with no education relied on traditional items. Having
      attended secondary school increased the odds of using commercial pads among
      married (adjusted odds ratios [AOR] 4.8, 95% confidence interval [CI] 3.25-7.12)
      and single females (AOR 2.17, 95% CI 1.04-4.55). Married females had lower odds
      of pad use if they reported early (<12 years of age) compared with later (>=18
      years) sexual debut (64% vs. 78%, AOR 0.45, 95% CI 0.21-0.97). Two-thirds of pad
      users received them from sexual partners. Receipt was lower among married females
      if partners were violent (AOR 0.67, 95% CI 0.53-0.85). Receipt among single
      females was higher if they had two or more sexual partners in the past year (AOR
      2.11, 95% CI 1.04-4.29). Prevalence of engaging in sex for money to buy pads was
      low (1.3%); however, 10% of 15-year-olds reported this, with girls <=15 having
      significantly higher odds compared with females over 15 (AOR 2.84, 95% CI 0.89
      9.11). The odds of having transactional sex for pads was higher among females
      having two or more partners in the past 12 months (AOR 4.86, 95% CI 2.06-11.43).
      CONCLUSIONS: Menstrual needs of impoverished females in rural LMICs settings
      likely leads to increased physical and sexual harms. Studies are required to
      strengthen knowledge and to evaluate interventions to reduce these harms.

PMID- 26296188
TI  - Evaluation of the Surface Characteristics of Various Implant Abutment Materials
      Using Confocal Microscopy and White Light Interferometry.
AB  - PURPOSE: The purpose of this study was to evaluate the surface characteristics of
      various implant abutment materials, such as of titanium alloy (Ti6Al4V; Ma),
      machined cobalt-chrome-molybdenum alloy (CCM), titanium nitride coating on a
      titanium alloy disc (TiN), anodic oxidized titanium alloy disc (AO), composite
      resin coating on a titanium alloy disc (Res), and zirconia disc (Zr), using
      confocal microscopy and white light interferometry. Measurements from the 2
      methods were evaluated to see if these methods would give equivalent results. The
      precision of measurements were evaluated by the coefficient of variation.
      MATERIALS AND METHODS: Five discs each of Ma, CCM, TiN, AO, Res, and Zr were
      used. The surface roughness was evaluated by confocal laser microscopy and white
      light interferometry. RESULTS: Confocal microscopy showed that the Res group
      showed significantly greater Ra, Rq, Rz, Sa, Sq, and Sz values compared with
      those of the Ma group (P < 0.05). The white light interferometry results showed
      that the Res group had significantly higher Ra, Rq, Rz, Rt, Sa, Sq, Sz, and Sdr
      values compared with the Ma group (P < 0.05). All the roughness parameters
      obtained from the 2 methods differed, and the Sa values of the Zr group from
      confocal microscopy were greater by 0.163 MUm than those obtained by white light
      interferometry. Least difference was seen in the TiN group where the difference
      was 0.058 MUm. CONCLUSION: Roughness parameters of different abutment materials
      varied significantly. Precision of measurement differed according to the
      characteristics of the material used. White light interferometry could be
      recommended for measurement of TiN and AO. Confocal microscopy gave more precise
      measurements for Ma and CCM groups. The optical characteristics of the surface
      should be considered before choosing the examination method.

PMID- 26296189
TI  - Current Phase II drugs under investigation for the treatment of limb ischemia.
AB  - INTRODUCTION: More than 20 million people in Europe suffer from peripheral
      arterial disease and nearly 3% develop critical limb ischemia (CLI). Without any
      medical treatment, CLI has poor prognosis, resulting in limb loss and high
      mortality rate. Until today, no systemic drug is available for the treatment of
      CLI and the gold standard method of treatment includes risk factor modification
      and open surgical or endovascular revascularization. Endovascular local drug
      delivery devices and novel antithrombotic agents, currently under investigation,
      aim to improve outcomes of revascularization procedures. The pioneering concept
      of therapeutic angiogenesis induced by gene and stem cell therapy has been
      proposed, in an attempt to increase ischemic tissue perfusion. AREAS COVERED:
      This review summarizes local and systemic pharmacological treatment of CLI using
      endovascular or pharmaco-biological therapy and focuses on Phase II trials
      available for these drugs. EXPERT OPINION: Novel endovascular technologies
      combining angioplasty and local drug-delivery continuously improve and will come
      to be standard of practice for the management of limb ischemia, while new
      antithrombotic agents will further improve outcomes. Therapeutic angiogenesis
      represents a safe and promising treatment option. The combination of
      revascularization with microcirculation improvement induced by gene or stem cell
      therapy could enhance limb salvage.

PMID- 26296190
TI  - Clavicle pain and reduction of incisional and fascial pain after posterior
      cervical surgery.
AB  - OBJECT: Incisional pain after posterior cervical spine surgery can be severe and
      very unpleasant to the patient. Ongoing incisional pain is one of the key
      disadvantages of posterior over anterior surgical approaches to the cervical
      spine. It prolongs hospital stays and delays return to work. In this study, the
      hypothesized that incisional pain in the immediate postoperative period is caused
      partially by tension on the skin as well as on the deep cervical fascia and the
      fascia overlying the trapezius, which are usually sewn together during closure.
      Reduction of this tension through retraction of the shoulders should therefore
      reduce pain as well as the amount of pain medication used in the early
      postoperative period. METHODS: In this prospective randomized controlled study,
      30 patients who had undergone posterior cervical spine surgery were randomized
      into 2 groups who either wore or did not wear a clavicle brace to retract the
      shoulders. Patients in the brace group began wearing the brace on postoperative
      day (POD) 4 and wore it continuously throughout the 30-day study period. Outcome
      was assessed by two measures: 1) the daily level of self reported pain according
      to the visual analog scale (VAS) and 2) the number of pain pills taken during the
      30-day postoperative period. RESULTS: Wearing a clavicle brace in the immediate
      postoperative period significantly reduced incisional pain and the amount of pain
      medication that patients took. Beginning on POD 4 and continuing until day POD
      13, the mean daily VAS score for pain was significantly lower in the brace group
      than in the control group. Furthermore, patients who wore the clavicle brace took
      less pain medication from POD 4 to POD 12. At this point the difference lost
      significance until the end of the study period. Four patients were randomized but
      did not tolerate wearing the brace. CONCLUSIONS: Patients who tolerated wearing
      the clavicle brace after posterior cervical spine surgery had reduced pain and
      used less pain medication.

PMID- 26296191
TI  - Thoracic primary central nervous system melanoma and lumbar schwannoma of complex
      neurocristopathy: case report.
AB  - Complex neurocristopathy, a disorder resulting from the aberrant proliferation of
      tissues derived from neural crest cells, has been previously reported in 2
      patients, both involving ophthalmic melanoma and other tumors. One patient had a
      periorbital neurofibroma, sphenoid wing meningioma, and choroid juxtapapillary
      meningioma. The other patient had a choroidal melanoma and an optic nerve sheath
      meningioma. The authors describe clinical and pathological findings in a patient
      who underwent resection of 2 distinct lesions: primary CNS melanoma at T-12 and
      an L-5 schwannoma. Clinical and histopathological findings of the case are
      reviewed. To the authors' knowledge, this is the first patient to present with
      complex neurocristopathy involving both a spinal melanoma and schwannoma. 

PMID- 26296192
TI  - Management of traumatic double-level spondyloptosis of the thoracic spine with
      posterior spondylectomy: case report.
AB  - Traumatic spondyloptosis of the thoracic spine is an uncommon injury. In most
      cases, spondyloptosis is confined to one vertebral body, whereas double-level
      spondyloptosis is extremely rare. Most patients who sustain traumatic
      spondyloptosis immediately become paraplegic, but in some cases neurological
      function is preserved. If this occurs, it is due to detachment of the pedicles
      from the corresponding vertebral body, resulting in spontaneous decompression of
      neural elements. Herein, the authors describe a case of undetected traumatic
      double-level spondyloptosis in the upper thoracic region in an adult male patient
      who was neurologically intact for 2 days but later became paraplegic. Initially,
      management of this pathology seemed a very challenging scenario. However, with
      review of the reconstructed CT images and reproduction of the injury on a plastic
      model, a posterior-only approach was chosen as an alternative operative solution
      for this catastrophic injury. Via this single-stage posterior approach, long
      segment pedicle screw/rod instrumentation resulted in successful reduction,
      restoration of alignment, and stabilization after 1-level posterior
      spondylectomy. To the best of the authors' knowledge, this is the first example
      reported in the literature of double-level spondyloptosis of the thoracic and the
      lumbar spine. This report describes the rationale, mechanism, and technical
      details afforded for reduction and stabilization of this rare injury. 

PMID- 26296193
TI  - Sagittal plane lumbar intervertebral motion during seated flexion-extension
      radiographs of 658 asymptomatic nondegenerated levels.
AB  - OBJECT: Evaluation of lumbar stability is fundamentally dependent on a clear
      understanding of normal lumbar motion. There are inconsistencies in reported
      lumbar motion across previously published studies, and it is unclear which
      provide the most reliable reference data. New technology now allows valid and
      reliable determination of normal lumbar intervertebral motion (IVM). The object
      of this study was to provide normative reference data for lumbar IVM and center
      of rotation (COR) using validated computer-assisted measurement tools. METHODS:
      Sitting flexion-extension radiographs were obtained in 162 asymptomatic
      volunteers and then analyzed using a previously validated and widely used
      computerized image analysis method. Each lumbar level was subsequently classified
      as "degenerated" or "nondegenerated" using the Kellgren-Lawrence classification.
      Of the 803 levels analyzed, 658 were nondegenerated (Kellgren-Lawrence grade <
      2). At each level of the lumbar spine, the magnitude of intervertebral rotation
      and translation, the ratio of translation per degree of rotation (TPDR), and the
      position of the COR were calculated in the nondegenerative cohort. Translations
      were calculated in millimeters and percentage endplate width. RESULTS: All
      parameters were significantly dependent on the intervertebral level. The upper
      limit of the 95% CIs for anteroposterior intervertebral translation in this
      asymptomatic cohort ranged from 2.1 mm (6.2% endplate width) to 4.6 mm (13.3%
      endplate width). Intervertebral rotation upper limits ranged from 16.3 degrees 
      to 23.5 degrees . The upper limits for TPDR ranged from 0.49% to 0.82% endplate
      width/degree. The COR coordinates were clustered in level-dependent patterns.
      CONCLUSIONS: New normal values for IVM, COR, and the ratio of TPDR in
      asymptomatic nondegenerative lumbar levels are proposed, providing a reference
      for future interpretation of sagittal plane motion in the lumbar spine.

PMID- 26296194
TI  - Amnesia and future thinking: Exploring the role of memory in the quantity and
      quality of episodic future thoughts.
AB  - OBJECTIVES: To examine the impact of memory accessibility on episodic future
      thinking. DESIGN: Single-case study of neurological patient HCM and an age
      matched comparison group of neurologically Healthy Controls. METHODS: We
      administered a full battery of tests assessing general intelligence, memory, and
      executive functioning. To assess autobiographical memory, the Autobiographical
      Memory Interview (Kopelman, Wilson, & Baddeley, 1990. The Autobiographical Memory
      Interview. Bury St. Edmunds, UK: Thames Valley Test Company) was administered.
      The Past Episodic and Future Episodic sections of Dalla Barba's Confabulation
      Battery (Dalla Barba, 1993, Cogn. Neuropsychol., 1, 1) and a specifically
      tailored Mental Time Travel Questionnaire were administered to assess future
      thinking in HCM and age-matched controls. RESULTS: HCM presented with a deficit
      in forming new memories (anterograde amnesia) and recalling events from before
      the onset of neurological impairment (retrograde amnesia). HCM's autobiographical
      memory impairments are characterized by a paucity of memories from Recent Life.
      In comparison with controls, two features of his future thoughts are apparent:
      Reduced episodic future thinking and outdated content of his episodic future
      thoughts. CONCLUSIONS: This article suggests neuropsychologists should look
      beyond popular conceptualizations of the past-future relation in amnesia via
      focussing on reduced future thinking. Investigating both the quantity and quality
      of future thoughts produced by amnesic patients may lead to developments in
      understanding the complex nature of future thinking disorders resulting from
      memory impairments. PRACTITIONER POINTS: We highlight the clinical importance of
      examining the content of future thoughts in amnesic patients, rather than only
      its quantitative reduction. We propose an explanation of how quantitative and
      qualitative aspects of future thinking could be affected by amnesia. This could
      provide a useful approach to understand clinical cases of impaired prospection.
      LIMITATIONS: Systematic group investigations are required to fully examine our
      hypothesis. Although the current study utilized typical future thinking measures,
      these may be limited and we highlight the need to develop clinically relevant
      measures of prospection.

PMID- 26296195
TI  - Novel bimodal iron oxide particles for efficient tracking of human neural stem
      cells in vivo.
AB  - AIMS: We validated novel bimodal iron oxide particles as substitute of
      ferumoxides for efficient labeling of human neural stem cells (NSCs). The
      dextrane-coated FeraTrack Direct (FTD)-Vio particles have additional far-red
      fluorophores for microscopic cell analysis. METHODS: MR relaxometry,
      spectrophotometric iron determination and microscopy are used for
      characterization in vitro and in vivo. RESULTS: Efficient uptake is not
      transfection agent-dependent. FTD-Vio594 labeling had no influence on viability,
      proliferation, migration and differentiation capacity. It allows MRI-based
      tracking of engrafted NSCs in mouse brain up to 11 days, complemented by
      bioluminescence imaging of firefly luciferase expressed by the engrafted cells.
      CONCLUSION: Our results highlight the FTD-Vio594 particles as safe and sensitive
      substitute of ferumoxides for longitudinal tracking of NSCs in preclinical
      studies.

PMID- 26296196
TI  - High-Fat Diet/Low-Dose Streptozotocin-Induced Type 2 Diabetes in Rats Impacts
      Osteogenesis and Wnt Signaling in Bone Marrow Stromal Cells.
AB  - Bone regeneration disorders are a significant problem in patients with type 2
      diabetes mellitus. Bone marrow stromal cells (BMSCs) are recognized as ideal seed
      cells for tissue engineering because they can stimulate osteogenesis during bone
      regeneration. Therefore, the aim of this study was to investigate the osteogenic
      potential of BMSCs derived from type 2 diabetic rats and the pathogenic
      characteristics of dysfunctional BMSCs that affect osteogenesis. BMSCs were
      isolated from normal and high-fat diet+streptozotocin-induced type 2 diabetic
      rats. Cell metabolic activity, alkaline phosphatase (ALP) activity,
      mineralization and osteogenic gene expression were reduced in the type 2 diabetic
      rat BMSCs. The expression levels of Wnt signaling genes, such as beta-catenin,
      cyclin D1 and c-myc, were also significantly decreased in the type 2 diabetic rat
      BMSCs, but the expression of GSK3beta remained unchanged. The derived BMSCs were
      cultured on calcium phosphate cement (CPC) scaffolds and placed subcutaneously
      into nude mice for eight weeks; they were detected at a low level in newly formed
      bone. The osteogenic potential of the type 2 diabetic rat BMSCs was not impaired
      by the culture environment, but it was impaired by inhibition of the Wnt
      signaling pathway, likely due to an insufficient accumulation of beta-catenin
      rather than because of GSK3beta stimulation. Using BMSCs derived from diabetic
      subjects could offer an alternative method of regenerating bone together with the
      use of supplementary growth factors to stimulate the Wnt signaling pathway. 

PMID- 26296197
TI  - Probucol-Induced alpha-Tocopherol Deficiency Protects Mice against Malaria
      Infection.
AB  - The emergence of malaria pathogens having resistance against antimalarials
      implies the necessity for the development of new drugs. Recently, we have
      demonstrated a resistance against malaria infection of alpha-tocopherol transfer
      protein knockout mice showing undetectable plasma levels of alpha-tocopherol, a
      lipid-soluble antioxidant. However, dietary restriction induced alpha-tocopherol
      deficiency is difficult to be applied as a clinical antimalarial therapy. Here,
      we report on a new strategy to potentially treat malaria by using probucol, a
      drug that can reduce the plasma alpha-tocopherol concentration. Probucol pre
      treatment for 2 weeks and treatment throughout the infection rescued from death
      of mice infected with Plasmodium yoelii XL-17 or P. berghei ANKA. In addition,
      survival was extended when the treatment started immediately after parasite
      inoculation. The ratio of lipid peroxidation products to parent lipids increased
      in plasma after 2 weeks treatment of probucol. This indicates that the protective
      effect of probucol might be mediated by the oxidative stressful environment
      induced by alpha-tocopherol deficiency. Probucol in combination with
      dihydroartemisin suppressed the proliferation of P. yoelii XL-17. These results
      indicated that probucol might be a candidate for a drug against malaria infection
      by inducing alpha-tocopherol deficiency without dietary alpha-tocopherol
      restriction. 

PMID- 26296199
TI  - Parkinson's disease psychosis: symptoms, management, and economic burden.
AB  - Parkinson's disease psychosis (PDP) is a costly,debilitating condition that
      generally develops several years after diagnosis of Parkinson's disease (PD).PD
      is the second-most common neurodegenerative disease, and it imposes a significant
      burden on the healthcare system. Non-motor symptoms commonly manifest in PD,
      contributing to the severity of a patient's disability. The neuropsychiatric
      symptoms that are common in PD can be a significant source of distress to
      patients and caregivers. Recent studies have shown that more than 50% of patients
      with PD will develop psychosis at some time over the course of the disease. The
      responsibility for caring for a person with PDP frequently falls on family
      members. Caregiver distress is frequently predicted when patients with PD have
      symptoms of psychosis.Hallucinations and delusions are independent predictors of
      nursing home placement for patients with PDP. The authors sought to examine total
      healthcare expenditures among patients with PDP compared with patients with PD
      without psychosis.All costs were higher for patients with PDP than for those with
      PD without psychosis and all-Medicare cohorts, with the highest cost
      differentials found in long-term care costs ($31,178 for PDP vs $14,461 forPD
      without psychosis), skilled nursing facility costs($6601 for PDP vs $2067 for PD
      without psychosis),and inpatient costs ($10,125 for PDP vs $6024 for PD without
      psychosis). Patients with PDP spent an average of 179 days in long-term care,
      compared with 83 days for patients with PD without psychosis. As expected, long
      term care utilization and expenditures were significantly higher for patients
      with PDP than for patients with PD without psychosis. Reducing long-term care
      utilization by patients with PDP may significantly lower the overall economic
      burden associated with PDP.

PMID- 26296198
TI  - The Association between HMGA1 rs146052672 Variant and Type 2 Diabetes: A
      Transethnic Meta-Analysis.
AB  - The high-mobility group A1 (HMGA1) gene has been previously identified as a
      potential novel candidate gene for susceptibility to insulin resistance and type
      2 diabetes (T2D) mellitus. For this reason, several studies have been conducted
      in recent years examining the association of the HMGA1 gene variant rs146052672
      (also designated IVS5-13insC) with T2D. Because of non-univocal data and non
      overlapping results among laboratories, we conducted the current meta-analysis
      with the aim to yield a more precise and reliable conclusion for this
      association. Using predetermined inclusion criteria, MEDLINE, PubMed, Web of
      Science, Scopus, Google Scholar and Embase were searched for all relevant
      available literature published until November 2014. Two of the authors
      independently evaluated the quality of the included studies and extracted the
      data. Values from the single studies were combined to determine the meta-analysis
      pooled estimates. Heterogeneity and publication bias were also examined. Among
      the articles reviewed, five studies (for a total of 13,789 cases and 13,460
      controls) met the predetermined criteria for inclusion in this meta-analysis. The
      combined adjusted odds ratio estimates revealed that the rs146052672 variant
      genotype had an overall statistically significant effect on increasing the risk
      of development of T2D. As most of the study subjects were Caucasian, further
      studies are needed to establish whether the association of this variant with an
      increased risk of T2D is generalizable to other populations. Also, in the light
      of this result, it would appear to be highly desirable that further in-depth
      investigations should be undertaken to elucidate the biological significance of
      the HMGA1 rs146052672 variant. 

PMID- 26296200
TI  - The Epidemiology of Hepatitis C Virus in the Fertile Crescent: Systematic Review
      and Meta-Analysis.
AB  - OBJECTIVE: To characterize hepatitis C virus (HCV) epidemiology in countries of
      the Fertile Crescent region of the Middle East and North Africa (MENA), namely
      Iraq, Jordan, Lebanon, Palestine, and Syria. METHODS: We systematically reviewed
      and synthesized available records of HCV incidence and prevalence following
      PRISMA guidelines. Meta-analyses were implemented using a DerSimonian-Laird
      random effects model with inverse weighting to estimate the country-specific HCV
      prevalence among the various at risk population groups. RESULTS: We identified
      eight HCV incidence and 240 HCV prevalence measures in the Fertile Crescent. HCV
      sero-conversion risk among hemodialysis patients was 9.2% in Jordan and 40.3% in
      Iraq, and ranged between 0% and 3.5% among other populations in Iraq over
      different follow-up times. Our meta-analyses estimated HCV prevalence among the
      general population at 0.2% in Iraq (range: 0-7.2%; 95% CI: 0.1-0.3%), 0.3% in
      Jordan (range: 0-2.0%; 95% CI: 0.1-0.5%), 0.2% in Lebanon (range: 0-3.4%; 95% CI:
      0.1-0.3%), 0.2% in Palestine (range: 0-9.0%; 95% CI: 0.2-0.3%), and 0.4% in Syria
      (range: 0.3-0.9%; 95% CI: 0.4-0.5%). Among populations at high risk, HCV
      prevalence was estimated at 19.5% in Iraq (range: 0-67.3%; 95% CI: 14.9-24.5%),
      37.0% in Jordan (range: 21-59.5%; 95% CI: 29.3-45.0%), 14.5% in Lebanon (range: 0
      52.8%; 95% CI: 5.6-26.5%), and 47.4% in Syria (range: 21.0-75.0%; 95% CI: 32.5
      62.5%). Genotypes 4 and 1 appear to be the dominant circulating strains.
      CONCLUSIONS: HCV prevalence in the population at large appears to be below 1%,
      lower than that in other MENA sub-regions, and tending towards the lower end of
      the global range. However, there is evidence for ongoing HCV transmission within
      medical facilities and among people who inject drugs (PWID). Migration dynamics
      appear to have played a role in determining the circulating genotypes. HCV
      prevention efforts should be targeted, and focus on infection control in clinical
      settings and harm reduction among PWID.

PMID- 26296201
TI  - Exploring the Structure of Human Defensive Responses from Judgments of Threat
      Scenarios.
AB  - How humans react to threats is a topic of broad theoretical importance, and also
      relevant for understanding anxiety disorders. Many animal threat reactions
      exhibit a common structure, a finding supported by human evaluations of written
      threat scenarios that parallel patterns of rodent defensive behavior to actual
      threats. Yet the factors that underlie these shared behavioral patterns remain
      unclear. Dimensional accounts rooted in Darwin's conception of antithesis explain
      many defensive behaviors. Across species, it is also clear that defensive
      reactions depend on specific situational factors, a feature long emphasized by
      psychological appraisal theories. Our study sought to extend prior investigations
      of human judgments of threat to a broader set of threats, including natural
      disasters, threats from animals, and psychological (as opposed to physical)
      threats. Our goal was to test whether dimensional and specific patterns of threat
      evaluation replicate across different threat classes. 85 healthy adult subjects
      selected descriptions of defensive behaviors that indicated how they would react
      to 29 threatening scenarios. Scenarios differed with respect to ten factors,
      e.g., perceived dangerousness or escapability. Across scenarios, we correlated
      these factor ratings with the pattern of defensive behaviors subjects endorsed. A
      decision tree hierarchically organized these correlation patterns to successfully
      predict each scenario's most common reaction, both for the original sample of
      subjects and a separate replication group (n = 22). At the top of the decision
      tree, degree of dangerousness interacted with threat type (physical or
      psychological) to predict dimensional approach/avoidance behavior. Subordinate
      nodes represented specific defensive responses evoked by particular contexts. Our
      ecological approach emphasizes the interplay of situational factors in evoking a
      broad range of threat reactions. Future studies could test predictions made by
      our results to help understand pathological threat processing, such as seen in
      anxiety disorders, and could begin to test underlying neural mechanisms. 

PMID- 26296202
TI  - Medical Decision-Making Incapacity among Newly Diagnosed Older Patients with
      Hematological Malignancy Receiving First Line Chemotherapy: A Cross-Sectional
      Study of Patients and Physicians.
AB  - BACKGROUND: Decision-making capacity to provide informed consent regarding
      treatment is essential among cancer patients. The purpose of this study was to
      identify the frequency of decision-making incapacity among newly diagnosed older
      patients with hematological malignancy receiving first-line chemotherapy, to
      examine factors associated with incapacity and assess physicians' perceptions of
      patients' decision-making incapacity. METHODS: Consecutive patients aged 65 years
      or over with a primary diagnosis of malignant lymphoma or multiple myeloma were
      recruited. Decision-making capacity was assessed using the Structured Interview
      for Competency and Incompetency Assessment Testing and Ranking Inventory-Revised
      (SICIATRI-R). Cognitive impairment, depressive condition and other possible
      associated factors were also evaluated. RESULTS: Among 139 eligible patients
      registered for this study, 114 completed the survey. Of these, 28 (25%, 95%
      confidence interval [CI]: 17%-32%) were judged as having some extent of decision
      making incompetency according to SICIATRI-R. Higher levels of cognitive
      impairment and increasing age were significantly associated with decision-making
      incapacity. Physicians experienced difficulty performing competency assessment
      (Cohen's kappa -0.54). CONCLUSIONS: Decision-making incapacity was found to be a
      common and under-recognized problem in older patients with cancer. Age and
      assessment of cognitive impairment may provide the opportunity to find patients
      that are at a high risk of showing decision-making incapacity.

PMID- 26296203
TI  - Multidisciplinary Views on Applying Explicit and Implicit Motor Learning in
      Practice: An International Survey.
AB  - BACKGROUND: A variety of options and techniques for causing implicit and explicit
      motor learning have been described in the literature. The aim of the current
      paper was to provide clearer guidance for practitioners on how to apply motor
      learning in practice by exploring experts' opinions and experiences, using the
      distinction between implicit and explicit motor learning as a conceptual
      departure point. METHODS: A survey was designed to collect and aggregate informed
      opinions and experiences from 40 international respondents who had demonstrable
      expertise related to motor learning in practice and/or research. The survey was
      administered through an online survey tool and addressed potential options and
      learning strategies for applying implicit and explicit motor learning. Responses
      were analysed in terms of consensus (>= 70%) and trends (>= 50%). A summary
      figure was developed to illustrate a taxonomy of the different learning
      strategies and options indicated by the experts in the survey. RESULTS: Answers
      of experts were widely distributed. No consensus was found regarding the
      application of implicit and explicit motor learning. Some trends were identified:
      Explicit motor learning can be promoted by using instructions and various types
      of feedback, but when promoting implicit motor learning, instructions and
      feedback should be restricted. Further, for implicit motor learning, an external
      focus of attention should be considered, as well as practicing the entire skill.
      Experts agreed on three factors that influence motor learning choices: the
      learner's abilities, the type of task, and the stage of motor learning (94.5%; n
      = 34/36). Most experts agreed with the summary figure (64.7%; n = 22/34).
      CONCLUSION: The results provide an overview of possible ways to cause implicit or
      explicit motor learning, signposting examples from practice and factors that
      influence day-to-day motor learning decisions.

PMID- 26296204
TI  - Electrically Stimulated Antagonist Muscle Contraction Increased Muscle Mass and
      Bone Mineral Density of One Astronaut - Initial Verification on the International
      Space Station.
AB  - BACKGROUND: Musculoskeletal atrophy is one of the major problems of extended
      periods of exposure to weightlessness such as on the International Space Station
      (ISS). We developed the Hybrid Training System (HTS) to maintain an astronaut's
      musculoskeletal system using an electrically stimulated antagonist to resist the
      volitional contraction of the agonist instead of gravity. The present study
      assessed the system's orbital operation capability and utility, as well as its
      preventative effect on an astronaut's musculoskeletal atrophy. METHODS: HTS was
      attached to the non-dominant arm of an astronaut staying on the ISS, and his
      dominant arm without HTS was established as the control (CTR). 10 sets of 10
      reciprocal elbow curls were one training session, and 12 total sessions of
      training (3 times per week for 4 weeks) were performed. Pre and post flight
      ground based evaluations were performed by Biodex (muscle performance), MRI
      (muscle volume), and DXA (BMD, lean [muscle] mass, fat mass). Pre and post
      training inflight evaluations were performed by a hand held dynamometer (muscle
      force) and a measuring tape (upper arm circumference). RESULTS: The experiment
      was completed on schedule, and HTS functioned well without problems. Isokinetic
      elbow extension torque (Nm) changed -19.4% in HTS, and -21.7% in CTR. Isokinetic
      elbow flexion torque changed -23.7% in HTS, and there was no change in CTR. Total
      Work (Joule) of elbow extension changed -8.3% in HTS, and +0.3% in CTR. For elbow
      flexion it changed -23.3% in HTS and -32.6% in CTR. Average Power (Watts) of
      elbow extension changed +22.1% in HTS and -8.0% in CTR. For elbow flexion it
      changed -6.5% in HTS and -4.8% in CTR. Triceps muscle volume according to MRI
      changed +11.7% and that of biceps was +2.1% using HTS, however -0.1% and -0.4%
      respectively for CTR. BMD changed +4.6% in the HTS arm and -1.2% for CTR. Lean
      (muscle) mass of the arm changed only +10.6% in HTS. Fat mass changed -12.6% in
      HTS and -6.4% in CTR. CONCLUSIONS: These results showed the orbital operation
      capability and utility, and the preventive effect of HTS for an astronaut's
      musculoskeletal atrophy. The initial flight data together with the ground data
      obtained so far will be utilized in the future planning of human space
      exploration.

PMID- 26296205
TI  - Relationships between Spatial Metrics and Plant Diversity in Constructed
      Freshwater Wetlands.
AB  - The diversity of plant species and their distribution in space are both thought
      to have important effects on the function of wetland ecosystems. However,
      knowledge of the relationships between plant species and spatial diversity
      remains incomplete. In this study, we investigated relationships between spatial
      pattern and plant species diversity over a five year period following the initial
      restoration of experimental wetland ecosystems. In 2003, six identical and
      hydrologically-isolated 0.18 ha wetland "cells" were constructed in former
      farmland in northeast Ohio. The systems were subjected to planting treatments
      that resulted in different levels of vascular plant species diversity among
      cells. Plant species diversity was assessed through annual inventories. Plant
      spatial pattern was assessed by digitizing low-altitude aerial photographs taken
      at the same time as the inventories. Diversity metrics derived from the
      inventories were significantly related to certain spatial metrics derived from
      the photographs, including cover type diversity and contagion. We found that
      wetlands with high cover type diversity harbor higher plant species diversity
      than wetlands with fewer types of patches. We also found significant
      relationships between plant species diversity and spatial patterning of patch
      types, but the direction of the effect differed depending on the diversity metric
      used. Links between diversity and spatial pattern observed in this study suggest
      that high-resolution aerial imagery may provide wetland scientists with a useful
      tool for assessing plant diversity. 

PMID- 26296206
TI  - Inability and Obligation in Moral Judgment.
AB  - It is often thought that judgments about what we ought to do are limited by
      judgments about what we can do, or that "ought implies can." We conducted eight
      experiments to test the link between a range of moral requirements and abilities
      in ordinary moral evaluations. Moral obligations were repeatedly attributed in
      tandem with inability, regardless of the type (Experiments 1-3), temporal
      duration (Experiment 5), or scope (Experiment 6) of inability. This pattern was
      consistently observed using a variety of moral vocabulary to probe moral
      judgments and was insensitive to different levels of seriousness for the
      consequences of inaction (Experiment 4). Judgments about moral obligation were no
      different for individuals who can or cannot perform physical actions, and these
      judgments differed from evaluations of a non-moral obligation (Experiment 7).
      Together these results demonstrate that commonsense morality rejects the "ought
      implies can" principle for moral requirements, and that judgments about moral
      obligation are made independently of considerations about ability. By contrast,
      judgments of blame were highly sensitive to considerations about ability
      (Experiment 8), which suggests that commonsense morality might accept a "blame
      implies can" principle. 

PMID- 26296207
TI  - Systematic and Molecular Basis of the Antibacterial Action of Quinoxaline 1,4-Di
      N-Oxides against Escherichia coli.
AB  - Quinoxaline 1,4-di-N-oxides (QdNOs) are widely known as potent antibacterial
      agents, but their antibacterial mechanisms are incompletely understood. In this
      study, the transcriptomic and proteomic profiles of Escherichia coli exposed to
      QdNOs were integratively investigated, and the results demonstrated that QdNOs
      mainly induced an SOS response and oxidative stress. Moreover, genes and proteins
      involved in the bacterial metabolism, cellular structure maintenance, resistance
      and virulence were also found to be changed, conferring bacterial survival
      strategies. Biochemical assays showed that reactive oxygen species were induced
      in the QdNO-treated bacteria and that free radical scavengers attenuated the
      antibacterial action of QdNOs and DNA damage, suggesting an oxidative-DNA-damage
      action of QdNOs. The QdNO radical intermediates, likely carbon-centered and aryl
      type radicals, as identified by electron paramagnetic resonance, were the major
      radicals induced by QdNOs, and xanthine oxidase was one of the QdNO-activating
      enzymes. This study provides new insights into the action of QdNOs in a
      systematic manner and increases the current knowledge of bacterial physiology
      under antibiotic stresses, which may be of great value in the development of new
      antibiotic-potentiating strategies. 

PMID- 26296208
TI  - Structure of the Glycosyltransferase Ktr4p from Saccharomyces cerevisiae.
AB  - In the yeast Saccharomyces cerevisiae, members of the Kre2/Mnt1 protein family
      have been shown to be alpha-1,2-mannosyltransferases or alpha-1,2
      mannosylphosphate transferases, utilising an Mn2+-coordinated GDP-mannose as the
      sugar donor and a variety of mannose derivatives as acceptors. Enzymes in this
      family are localised to the Golgi apparatus, and have been shown to be involved
      in both N- and O-linked glycosylation of newly-synthesised proteins, including
      cell wall glycoproteins. Our knowledge of the nine proteins in this family is
      however very incomplete at present. Only one family member, Kre2p/Mnt1p, has been
      studied by structural methods, and three (Ktr4p, Ktr5p, Ktr7p) are completely
      uncharacterised and remain classified only as putative glycosyltransferases. Here
      we use in vitro enzyme activity assays to provide experimental confirmation of
      the predicted glycosyltransferase activity of Ktr4p. Using GDP-mannose as the
      donor, we observe activity towards the acceptor methyl-alpha-mannoside, but
      little or no activity towards mannose or alpha-1,2-mannobiose. We also present
      the structure of the lumenal catalytic domain of S. cerevisiae Ktr4p, determined
      by X-ray crystallography to a resolution of 2.2 A, and the complex of the enzyme
      with GDP to 1.9 A resolution. 

PMID- 26296210
TI  - Gut Homing Molecule Regulation of the Pathogenesis and Treatment of Inflammatory
      Bowel Diseases.
AB  - Inflammatory bowel disease is a chronic, debilitating immunological disorder for
      which there are few effective treatments. New therapies targeting gut homing
      molecules, such as CCR9 and alpha4beta7, are currently in development, with some
      of these reaching clinical trials. Gut-trophic molecules and their receptors are
      critical to the development of both tolerant and inflammatory immune responses in
      the gut. However, we know little regarding the function of homing molecules as it
      relates to IBD. Data have suggested both pathological and protective roles for
      gut homing molecules in IBD development and maintenance. In addition, recent
      research findings have suggested that chemokines can influence T cell
      differentiation and function. Given the current clinical relevance, it is
      essential to obtain a better understanding of the role of gut homing molecules in
      the regulation of IBD. 

PMID- 26296209
TI  - Natural Killer Cells Mediate Protection against Yersinia pseudotuberculosis in
      the Mesenteric Lymph Nodes.
AB  - Natural killer cells play a crucial role in the initial defense against bacterial
      pathogens. The crosstalk between host cells infected with intracellular pathogens
      and NK cells has been studied intensively, but not much attention has been given
      to characterize the role of NK cells in the response to extracellular bacterial
      pathogens such as yersiniae. In this study we used antibody-mediated NK cell
      depletion to address the importance of this immune cell type in controlling a Y.
      pseudotuberculosis infection. Analysis of the bacterial counts was used to follow
      the infection and flow cytometry was performed to characterize the composition
      and dynamic of immune cells. Depletion of NK cells led to higher bacterial loads
      within the mesenteric lymph nodes. We further show that in particular CD11b+
      CD27+ NK cells which express higher levels of the activation marker CD69 increase
      within the mesenteric lymph nodes during a Y. pseudotuberculosis infection.
      Moreover, in response to the activation NK cells secrete higher levels of IFNy,
      which in turn triggers the production of the proinflammatory cytokine TNFalpha.
      These results suggest, that NK cells aid in the clearance of Y.
      pseudotuberculosis infections mainly by triggering the expression of
      proinflammatory cytokines manipulating the host immune response. 

PMID- 26296211
TI  - Tissue Stem Cells and Uterine Physiology and Pathology.

PMID- 26296212
TI  - Japanese Encephalitis in Assam, India: Need to Increase Healthcare Workers'
      Understanding to Improve Health Care.
AB  - INTRODUCTION: Japanese encephalitis (JE) is a major cause of high morbidity and
      mortality in several states across India. However, in 2014, a sharp rise was
      observed in the number of cases of JE in north-eastern Assam state, and 51% of
      the total cases of JE in India were reported from the Assam in the same year. In
      this regard, a study was conducted to evaluate the knowledge and attitudes of
      healthcare workers in Darrang, a district of Assam highly affected by JE.
      METHODS: A cross sectional study was conducted for 2 months among HCWs in the
      major district hospital of Darrang, Assam. A pre-tested, self-administered
      questionnaire was used to collect data from the participants. Convenience
      sampling approach was used to collect data from different departments of the
      hospitals. Descriptive and logistic regression analyses were used to express the
      results. RESULTS: The knowledge of HCWs regarding JE was poor with a mean
      knowledge score of 11.02+/-2.39 (out of 17), while their attitudes were positive
      with a mean attitudes score of 43.16+/- 2.47 (ranging from 13 to 52). Overall,
      40.4% and 74.3% of participants demonstrated good knowledge and positive
      attitudes respectively. Cut-off score for good knowledge and positive attitudes
      toward JE was set as >=12 and >40 respectively. Older participants (40-49 years)
      and experienced workers (>10 years) were significantly associated with good
      knowledge as compared to their referent group (p<0.05), while knowledge of nurses
      and other orderlies were significantly lower than physicians (p<0.01). Similar
      factors were associated with the positive attitudes of the participants with the
      exception of experience. Television was the major source of information regarding
      JE reported by HCWs (79%). CONCLUSION: Although the knowledge was not optimized,
      HCWs exhibited positive attitudes towards JE. Future research is required to
      design, implement and evaluate interventions to improve the knowledge of JE among
      HCWs.

PMID- 26296213
TI  - Use of Low-profile Palmar Internal Fixation in Digital Replantation.
AB  - There are multiple surgical techniques to stabilize the bone in digital
      replantation. Various criteria need to be considered when choosing appropriate
      bony fixation including operative time, ease of exposure, stability, limitation
      of the area of dissection, and reproducibility. We describe our technique using
      internal fixation with a low-profile plate on the palmar aspect of the proximal
      or middle phalanx during replantation of a digit. This technique allows coverage
      of the plate with no risk of compromising the dorsal venous anastomosis. In our
      experience, using this technique we have observed no complications including no
      secondary displacement of the fragments or extensor tendon rupture and no
      incidence of infection. In addition, this technique allows adequate bony fixation
      to enable an early active range of motion rehabilitation program. 

PMID- 26296214
TI  - Well-camouflaged Skin Graft Donor Sites in the Hand.
AB  - Three full-thickness skin graft sites within the hand where the donor sites are
      well blended with surrounding skin contour and crease are described. Two of these
      donor sites are located within the digit and these provide nonglaborous skin for
      small defects of the hand, whereas the third donor site along the palmar crease
      provides glaborous skin. These donor sites provide ease of access, minimal
      morbidity, and well-matched skin for resurfacing of small defects around the
      hand. The indications, contraindications, and technical points of each donor site
      are discussed. 

PMID- 26296215
TI  - What's New in Pediatric Flatfoot?
AB  - BACKGROUND: Children with flatfeet are frequently referred to pediatric
      orthopaedic clinics. Most of these patients are asymptomatic and require no
      treatment. Care must be taken to differentiate patients with flexible flatfeet
      from those with rigid deformity that may have underlying pathology and have need
      of treatment. Rigid flatfeet in infants may be attributable to a congenital
      vertical talus (CVT); whereas those in older children and adolescents may be due
      to an underlying tarsal coalition. We performed a review of the recent literature
      regarding evaluation and management of pediatric flatfeet to discuss new findings
      and suggest areas where further research is needed. METHODS: We searched the
      PubMed database for all papers related to the treatment of pediatric flatfoot,
      tarsal coalition, and CVT published from January 1, 2011 to December 31, 2014,
      yielding 85 English language papers. RESULTS: A total of 18 papers contributed
      new or interesting findings. CONCLUSIONS: The pediatric flexible flatfoot (FFF)
      remains poorly defined, making the understanding, study, and treatment of the
      condition extremely difficult.Pediatric FFF is often unnecessarily treated. There
      is very little evidence for the efficacy of nonsurgical intervention to affect
      the shape of the foot or to influence potential long-term disability for children
      with FFF. The treatment of tarsal coalition remains challenging, but short-term
      and intermediate-term outcome studies are satisfactory, whereas long-term outcome
      studies are lacking. Management of the associated flatfoot deformity may be as
      important as management of the coalition itself. The management of CVT is still
      evolving; however, early results of less invasive treatment methods seem
      promising. LEVEL OF EVIDENCE: Level 4-literature review.

PMID- 26296216
TI  - Gait Pattern and Lower Extremity Alignment in Children With Diastrophic
      Dysplasia.
AB  - BACKGROUND: The aim of this study was to describe the dynamic lower extremity
      alignment in children with diastrophic dysplasia (DD) by 3-dimensional gait
      analyses. Our main hypothesis was that gait kinematics and kinetics are different
      than the age-normalized population and patellar dislocation can alter the gait in
      patients with DD. METHODS: A retrospective review of clinical data and
      radiographs was conducted for patients with DD who had gait analysis before lower
      extremity skeletal surgery excluding foot procedures. Lower extremity range of
      motion was measured. The Pediatric Outcomes Data Collection Instrument (PODCI)
      was administered to parents to evaluate their children's functional status. Gait
      laboratory data were collected to compare the hip and knee kinematics in cases
      with and without patellar dislocation. Anteroposterior standing radiographs were
      taken for all patients to assess the correlation between measurements (clinical,
      radiologic, and gait) for coronal knee alignment. RESULTS: Thirty lower
      extremities of 15 children (7 females and 8 males) were evaluated. The mean age
      was 7.4+/-3 years, the mean height was 97.7+/-15 cm (z=-5.1), and the mean weight
      was 20.6+/-6.2 kg (z=-0.8). The DD PODCI subscores were statistically
      significantly lower (P<0.05) than the average stature for developing children,
      except for the happiness score. Gait analysis, compared between all DD and an age
      normalized average stature group, showed decreased forward velocity, step length,
      and stride length with an increased average forward tilt of the trunk and pelvis,
      hip flexion, hip adduction, and internal rotation (P<0.001). Delta hip and knee
      motion were also decreased (P<0.001). The patella was dislocated in 19 (63.3%)
      and central in 11 (36.6%) knees. Comparison of the minimum knee and hip flexion
      at the stance phase demonstrated increased crouch gait in the patellar
      dislocation group (P<0.001). Knee alignment measurements between clinical
      examination and gait analysis showed moderate correlation (r, 0.476; P=0.008).
      CONCLUSIONS: Children with DD demonstrated lower PODCI subscores except for
      happiness. Gait analysis showed limited lower extremity function of the children
      with DD in our study group. Patella dislocation group had increased crouch gait.
      LEVELS OF EVIDENCE: Level III-diagnostic study.

PMID- 26296217
TI  - Temperature Change When Drilling Near the Distal Femoral Physis in a Skeletally
      Immature Ovine Model.
AB  - BACKGROUND: The possibility of physeal injury during anterior cruciate ligament
      reconstruction in the pediatric population is a concern. The purpose of this
      study was to determine whether drilling at or near the physis could cause a
      temperature increase that could trigger chondrolysis. METHODS: Skeletally
      immature cadaveric lamb distal femurs were used for this study and randomly
      placed in 1 of 6 groups (n=10 in each group). We examined the 8 and 10 mm
      Flipcutter at a distance of 0.5 mm from the physis and an 8 and 10 mm acorn
      tipped reamer at a distance of 0.5 and 3.0 mm from the physis. During drilling,
      temperature change at the distal femoral physis was continuously measured until
      the temperature decreased to the original value. RESULTS: An interreamer
      comparison yielded a significant difference when drilling 0.5 mm from the physis
      (P=0.001). Pair-wise Mann-Whitney post hoc tests were performed to further
      evaluate the differences among the groups. The 8 mm FlipCutter had a
      significantly higher maximum temperature (39.8+/-1.4 degrees C) compared with the
      10 mm FlipCutter (38.0+/-0.6 degrees C, P=0.001), 8 mm acorn-tipped reamer
      (38.1+/-0.9 degrees C, P=0.007), and 10 mm acorn-tipped reamer (37.5+/-0.3
      degrees C, P<0.001). CONCLUSIONS: The risk of thermal-induced injury to the
      physis is low with an all epiphyseal drilling technique, when a traditional acorn
      tipped reamer over a guidepin is utilized, even if the drilling occurs very close
      to the physis. In addition, the risk of drilling with a FlipCutter is low, but
      may be greater than a traditional reamer. CLINICAL RELEVANCE: Thermal-induced
      necrosis is a realistic concern, due to the characteristics of the distal femoral
      physis, and the propensity for this physis to respond poorly to injury. Our study
      supports that drilling near the physis can be done safely, although smaller
      reamers and nontraditional designs may generate higher heat. LEVEL OF EVIDENCE:
      Level I-basic science.

PMID- 26296218
TI  - Quality, Safety, and Value in Pediatric Orthopaedic Surgery.
AB  - Enhancing patient safety and the quality of care continues to be a focus of
      considerable public and professional interest. We have made dramatic strides in
      our technical ability to care for children with pediatric orthopaedic problems,
      but it has become increasingly obvious that there are also significant
      opportunities to improve the quality, safety, and value of the care we deliver.
      The purpose of this article is to introduce pediatric orthopaedic surgeons to the
      rationale for and principles of quality improvement and to provide an update on
      quality, safety, and value projects within Pediatric Orthopaedic Society of North
      America. 

PMID- 26296220
TI  - Addressing the Global Disparities in the Delivery of Pediatric Orthopaedic
      Services: Opportunities for COUR and POSNA.
AB  - The burden of musculoskeletal conditions, especially injuries, is increasing in
      low-income and middle-income countries. Road traffic injuries have become
      epidemic. There are multiple barriers to accessing surgical services at both the
      individual (utilization) and the health system (availability) levels, and
      deficiencies in education and training of health providers. Specialty societies
      such as the Pediatric Orthopaedic Society of North America (POSNA) have an
      opportunity to play an important role through teaching and training. The POSNA
      Children's Orthopedics in Underserved Regions (COUR) committee has supported the
      Visiting Scholars Program, which invites surgeons from the developing world to
      attend a scientific meeting and facilitates the scholar's visit to North American
      pediatric orthopaedic centers. POSNA members have held global educational courses
      that support an educational exchange between lecturers and attendees. The COUR
      web site allows for submission of trip reports that document successes and
      obstacles experienced by members performing overseas clinical care and teaching.
      The web site also provides educational resources relevant to providing care in
      these environments. POSNA collaborates with other societies, such as the American
      Academy of Orthopaedic Surgeons and the Society of Military Orthopaedic Surgeons,
      to provide education in disaster management. In addition to increasing member
      involvement, specialty societies have the opportunity for continued data
      collection from overseas care, application of US registry data to disease
      processes in the developing world, and further collaboration with one another. 

PMID- 26296219
TI  - Infection as a Complication of Intrathecal Baclofen Treatment in Children With
      Cerebral Palsy.
AB  - BACKGROUND: Children with cerebral palsy (CP) and spasticity are often managed
      with intrathecal baclofen treatment (ITB). Complications of ITB include infection
      at the pump or catheter site and late complications as well as revisions of the
      pump and catheter because of events such as battery expiration or implant
      malfunction. The goal of this study is to report the short-term and long-term
      incidence, risk factors, and treatment outcomes of ITB infections in children.
      METHODS: This was a retrospective review of 294 children with CP. The number of
      ITB surgeries per patient, risk of infection for primary and secondary ITB
      related procedures, microorganisms responsible, and associated factors, such as
      concurrent orthopaedic interventions, medical comorbidities, and subsequent
      management of ITB-related infections, were evaluated. RESULTS: Infection occurred
      in 28/294 patients (9.5%) with a 4.9% rate per procedure. There were 14 acute
      (within 90 d of surgery) and 14 late infections. The infection risk per ITB
      procedure was 2.4%. Risk of late infection over 5-year mean follow-up was 0.95%
      per year. Pump removal with acute contralateral implantation was the most
      successful treatment of infections. Gross Motor Function Classification System
      level V and G-tube were the main risk factors for infection. A total of 133
      concurrent orthopaedic procedures were performed during 277 ITB procedures with
      no increased risk of infection. CONCLUSIONS: ITB in children with CP has a
      relatively low and manageable risk of infection. It is important to always
      consider infection as a complication with ITB because with prompt treatment the
      positive impact of ITB is still possible. It is safe to perform concurrent
      orthopaedic procedures with ITB procedures. LEVELS OF EVIDENCE: Level III
      therapeutic study.

PMID- 26296221
TI  - Switching to a Pediatric Dose O-Arm Protocol in Spine Surgery Significantly
      Reduced Patient Radiation Exposure.
AB  - BACKGROUND: Intraoperative computed tomography and image-guided navigation
      improve the accuracy of screw placement. Radiation exposure to the patient
      remains a primary drawback. The objective of the present study was to compare the
      total intraoperative radiation dose and assess the resultant image quality for O
      arm-assisted pedicle screw insertion, among 3 protocols: default (manufacturer
      recommended), institutional (reduced dose utilized in our institution), and
      pediatric (new protocol with lowest dose). METHODS: Thirty-seven consecutive
      patients under the age of 18 years underwent posterior instrumentation of the
      spine and underwent an intraoperative O-arm scan. Techniques (kV and mAs) for
      default and institutional dose settings were manually adjusted based on spinal
      level and body weight. Pediatric dose techniques were 80 kV/80 mAs with no
      adjustment for level or weight. The number of scans repeated because of
      inadequate imaging was assessed, and the mean estimated effective dose between
      the 3 protocols was compared. RESULTS: Sixty-eight scans were performed in 37
      consecutive patients with mean age of 14 years and mean weight of 55 kg. For
      reference, the effective radiation dose of a chest x-ray is approximately 0.10
      mSv. Use of the default protocol resulted in higher mean effective dose per scan
      of 4.65 mSv, whereas institutional protocol resulted in 2.37 mSv. The pediatric
      protocol reduced the mean dose to 0.65 mSv. The total effective dose per surgery
      was: 1.17 mSv (pediatric), 3.83 mSv (institutional), and 12.79 mSv (default)
      (P<0.0001 each). All scans lead to satisfactory image quality except in 1 patient
      >100 kg with stainless steel implants. There were no neurological or other
      implant-related complications. The pediatric protocol resulted in satisfactory
      image quality with the lowest total radiation dose, only 1/10 of that of the
      default protocol. CONCLUSIONS: We successfully switched to a pediatric low-dose O
      arm protocol in clinical practice, reducing the dose to <1/4 of the mean annual
      natural background radiation. This may allow use of intraoperative computed
      tomography and navigation for pedicle screw placement without excessive radiation
      exposure to young patients. LEVEL OF EVIDENCE: Level III-retrospective
      comparative study.

PMID- 26296222
TI  - Comments on Minimum of 2 Years Instead of Reporting Results at the Conclusion of
      Treatment (Hefferman et al, "Treatment of Femur Fractures in Young Children: A
      Multicenter Comparison of Flexible Intramedullary Nails to Spica Casting in Young
      Children Aged 2 to 6 Years." J Pediatr Orthop. 2015;35(2):126-129.

PMID- 26296223
TI  - Management Protocol For Shaft Femur Fractures in Preschool Age Children: Do We
      Need to Rethink?

PMID- 26296224
TI  - Surgical Techniques for Displaced Radial Neck Fractures: Predictive Factors of
      Functional Results.
AB  - BACKGROUND: Fractures of the radial neck represent about 1% of all childhood
      fractures and 5% to 10% of childhood traumatic lesions involving the elbow.
      Management of these fractures in children is still controversial. Intramedullary
      percutaneous nail reduction (Metaizeau technique) is considered the most
      effective surgical technique because of its excellent results and easy learning
      curve. Complications may arise, however, especially in Bohler technique, in which
      a percutaneous pin is placed over the radial head. When this technique does not
      provide correct reduction, open reduction must be performed. Because open
      reduction is traditionally associated with a high risk of complications, however,
      its use is restricted to severely displaced fractures and only when the
      percutaneous techniques have failed or their application contraindicated because
      of associated injuries to the distal radius. METHODS: In this retrospective
      study, we evaluated 51 children between the ages of 6 and 15 years who presented
      to our institution from 1996 to 2012 with Metaizeau-modified Judet grades 3, 4a,
      and 4b radial head fractures. The surgical techniques used were closed reduction
      and casting under general anesthesia (n=7), closed reduction and intramedullary
      nailing using Metaizeau technique (n=27), and Metaizeau technique and open
      reduction with intramedullary nailing (n=17). Functional results of the 3
      surgical techniques were evaluated using the Mayo Elbow Performance Score (MEPS)
      and compared by modified Judet classification using chi analysis. RESULTS: No
      statistic significant association was found between type of surgery and final
      MEPS was observed (P=0.110). However, a significant association was found between
      initial modified Judet grade and final MEPS. CONCLUSIONS: In the present study,
      final functional outcome seems to be not affected by open reduction but was
      significantly associated with initial modified Judet grade. LEVEL OF EVIDENCE:
      Level III-retrospective study comparing closed and open reduction techniques,
      performed at the same institution.

PMID- 26296225
TI  - Surgical Reconstruction of Metatarsal Type Preaxial Polydactyly Using an
      Amalgamating Osteotomy.
AB  - BACKGROUND: Polydactyly of the foot is a relatively common condition.
      Approximately 15% of cases are preaxial, with one third of these cases involving
      duplication of the metatarsal [metatarsal type preaxial polydactyly
      (MTPP)].Surgical reconstruction of polydactyly is indicated to improve shoe
      tolerance. Reconstruction of MTPP has traditionally involved resection of the
      hypoplastic lateral ray in addition to soft tissue reconstruction to correct
      hallux varus. Poor postoperative results have frequently been reported, primarily
      due to residual hallux varus. We present a novel surgical technique for the
      treatment of children with MTPP presenting with a cosmetic lateral hallux,
      involving an amalgamating osteotomy that permits retention of the stable medial
      metatarsotarsal joint while avoiding the complication of residual hallux varus.
      METHODS: This was a retrospective case series describing the surgical technique
      of an amalgamating osteotomy in the treatment of patients with MTPP and a
      cosmetic lateral hallux. The surgical technique involves corresponding metatarsal
      osteotomies of the medial and lateral halluces, with amalgamation of the
      metatarsals and ablation of the residual medial hallux, without the need for
      extensive soft tissue reconstruction. Clinical and radiologic outcomes were
      evaluated at a minimum of 2 years postoperatively in 2 patients who underwent
      this technique. RESULTS: Two children, 1 female and 1 male, underwent an
      amalgamating osteotomy at the age of 31 and 18 months, respectively. At latest
      follow-up, 7.3 and 2.8 years after osteotomy, respectively, both patients
      displayed an excellent functional result according to the Phelps and Grogan
      clinical outcome scale. Plain radiographs in both cases demonstrated a well
      aligned first ray with no growth abnormality and no hallux varus. CONCLUSIONS: We
      have presented a novel surgical technique for the reconstruction of MTPP
      presenting with a cosmetic lateral hallux, involving an amalgamating osteotomy
      without extensive soft tissue reconstruction. This simple technique maintains the
      stable medial metatarsotarsal joint, permits ongoing longitudinal metatarsal
      growth, and avoids the complication of hallux varus. LEVEL OF EVIDENCE: Level IV
      case series.

PMID- 26296226
TI  - Beam Projection Effect in the Radiographic Evaluation of Ankle Valgus Deformity
      Associated With Fibular Shortening.
AB  - BACKGROUND: Fibular shortening is one of the most common causes of ankle valgus
      deformity in children, and is frequently observed in patients with hereditary
      multiple exostoses (HME). It has been observed that the lateral distal tibial
      angle (LDTA) measured on the teleoradiograph differs from that on the ankle
      anteroposterior (AP) radiograph. The effect of the beam projection angle in the
      measurement of ankle valgus deformity associated with fibular shortening in HME
      patients was investigated. METHODS: Fourteen ankles showing valgus deformity
      associated with fibular shortening from 14 HME patients comprised the short
      fibula group. Nineteen ankles with normal ankle alignment from 19 patients
      comprised the control group. The LDTA on the AP radiograph, teleoradiograph, and
      3 coronal planes of 3-dimensional computed tomographic scans were measured and
      compared. RESULTS: In the short fibula group, the LDTA measured on the ankle AP
      radiograph was significantly larger than that on the teleoradiograph (79.6+/-4.3
      vs. 75.0+/-6.2 degrees, P=0.001), whereas there was no significant difference in
      the control group (P=0.36). In the short fibula group, the LDTAs measured on the
      3 coronal planes of 3-dimensional computed tomography showed that the ankle
      valgus measurement significantly increased from anterior to posterior planes
      (P=0.001), whereas there was no significant difference in the control group
      (P=0.85). CONCLUSIONS: Measurement of ankle valgus deformity depends on the
      direction of beam projection and ankle valgus deformity is more severe in the
      posterior coronal plane of the ankle joint. This discrepancy should be taken into
      consideration in the planning of ankle valgus deformity management. LEVEL OF
      EVIDENCE: Level IV-diagnostic.

PMID- 26296227
TI  - Outcomes of Hemiepiphyseal Stapling for Genu Valgum Deformities in Patients With
      Multiple Hereditary Exostoses: A Comparative Study of Patients With Deformities
      of Idiopathic Cause.
AB  - BACKGROUND: Patients with multiple hereditary exostoses (MHE) frequently present
      with a genu valgum deformity. Temporary hemiepiphysiodesis, such as
      hemiepiphyseal stapling, is a relatively safe surgical method to correct angular
      deformities in skeletally immature patients, but its outcomes for genu valgum
      deformity in MHE patients have not been extensively reported. We investigated the
      outcomes of hemiepiphyseal stapling in MHE patients (MHE group) and compared
      those with the outcomes in patients with idiopathic deformities (idiopathic
      group) after adjusting for potential bias. METHODS: Data from 70 limbs with genu
      valgum deformity (15 MHE and 55 idiopathic), which had undergone hemiepiphyseal
      stapling, were retrospectively reviewed. The outcomes were focused on the
      achievement of satisfactory correction and the velocity of correction. The
      independent effects of each characteristic on each outcome were investigated
      using multivariate analyses. The outcomes between the groups were also compared
      after 1:2 matching using propensity score analysis. RESULTS: The mean valgus
      angle of the MHE group was 7.4+/-4.1 degrees at stapling and was corrected to
      1.3+/-3.0 degrees at staple removal. The rate of satisfactory corrections was not
      different between the MHE and idiopathic groups (67% and 70%, respectively,
      P=0.820). However, the correction velocity was significantly lower in the MHE
      group than in the idiopathic group on both multivariate analysis (P=0.001) and
      matching comparison (4.4 vs. 7.9 degrees/y, P<0.001). The duration of correction
      was longer in the MHE group than in the idiopathic group by approximately half a
      year (1.5+/-0.6 vs. 0.9+/-0.3 y, respectively, P=0.003). CONCLUSIONS: In MHE
      patients with genu valgum deformity, satisfactory correction can be achieved by
      hemiepiphyseal stapling and is comparable with that seen in idiopathic patients.
      However, the MHE group showed lower correction velocity and required a longer
      time by about one half year for correction compared with the idiopathic group.
      Temporary hemiepiphysiodesis should be considered at an earlier age for patients
      with MHE compared with those with idiopathic deformity. LEVEL OF EVIDENCE: Level
      III-prognostic study.

PMID- 26296228
TI  - Pediatric Orthopaedic Providers' Views on Transition From Pediatric to Adult
      Care.
AB  - BACKGROUND: Surgical specialties are underrepresented in the discussions
      regarding transition and transfer of patients to adult care. We sought the
      pediatric orthopaedic perspective on types of patients seen into adulthood, age
      cut-offs, triggers for transfer, and barriers to transition. We examined provider
      demographic factors that may influence perspectives. METHODS: An internet-based
      survey was sent to all members of the Pediatric Orthopaedic Society of North
      America and the Pediatric Orthopaedic Practitioner Society. Responses were
      voluntary and anonymous. RESULTS: Response rates were 27% for the Pediatric
      Orthopaedic Society of North America and 24% for the Pediatric Orthopaedic
      Practitioner Society. Most respondents (70%) care for patients over the age of 25
      years and many (35%) for patients over the age of 40. The most common conditions
      cared for were neuromuscular and congenital disorders. Respondents who worked in
      a fully salaried model reported caring for fewer of these adult patients compared
      with those working in other types of payment structure (P<0.001). Respondents
      working in free-standing children's hospitals reported fewer patients over 30
      years old compared with nonchildren's hospital settings (P<0.001). There were no
      significant differences between profit-based and nonprofit settings. The top
      triggers for transfer to adult providers were: (1) adult comorbidities; (2)
      transition to medical specialist; and (3) institutional policy. The top barriers
      to transfer were: (1) lack of qualified adult providers; (2) institutional
      policy; and (3) on-going surgical issues. CONCLUSIONS: Many providers care for
      older patients, often using external triggers for transfer to adult care.
      Financial considerations may need to be further explored. Variation in care may
      be aided by national society guidelines. LEVEL OF EVIDENCE: Level III-survey
      research.

PMID- 26296229
TI  - Posterior C1-C2 Fixation Using Absorbable Suture for Type II Odontoid Fracture in
      2-Year-Old Child: Description of a New Technique and Literature Review.
AB  - : Odontoid synchondrosis fractures are rare in children, even though they are the
      more common cervical fracture in children less than 7 years old. Nonoperative
      treatment with external orthosis immobilization is the treatment of choice for
      stable undisplaced or minimally displaced injuries. In unstable fractures, when
      reduction cannot be achieved or maintained, surgical fixation is recommended. We
      report a 2-year-old boy with an unstable fracture of the odontoid treated
      surgically using an absorbable monofilament suture for C1-C2 interlaminar
      fixation without bone grafting. This suture was strong enough to provide the
      stability necessary to allow healing of the synchondrosis and the delayed
      resorption of the suture was followed by complete restoration of the mobility
      between C1 and C2. This case illustrates that surgical stabilization using an
      absorbable suture in young children with an unstable odontoid fracture is a safe
      and effective alternative to other surgical techniques. LEVEL OF EVIDENCE: Level
      III.

PMID- 26296230
TI  - Intramolecular Hydrogen Bonding in Methyl Lactate.
AB  - The intramolecular hydrogen bonding in methyl lactate was studied with Fourier
      transform infrared (FTIR) spectroscopy, intracavity laser photoacoustic
      spectroscopy, and cavity ring-down spectroscopy. Vapor phase spectra were
      recorded in the DeltavOH = 1-4 OH-stretching regions, and the observed OH
      stretching transitions were compared with theoretical results. Transition
      frequencies and oscillator strengths were obtained using a one-dimensional
      anharmonic oscillator local mode model with potential energy and dipole moment
      surfaces calculated at the CCSD(T)-F12a/VDZ-F12 level. The three most abundant
      conformers of methyl lactate all appear to possess an intramolecular hydrogen
      bond, with the hydroxyl group forming a hydrogen bond with either the carbonyl or
      ester oxygen. The intramolecular hydrogen bonds were investigated theoretically
      by analyses based on electron density topology, natural bond orbital analysis,
      and visualization of the electrostatic potential energy. 

PMID- 26296232
TI  - Investigation of porous silica nanostructures in diatoms isolated from Kurichi
      and Sulur lakes of Coimbatore, India using field emission scanning electron
      microscopy.
AB  - Diatoms are unicellular algae that possess cell wall made of silica. These
      diatoms play a pivotal role in synthesis of variety of silica nanostructures and
      have adorning morphology in nature. In the present study, we have used field
      emission scanning electron microscopy (FE-SEM) to investigate their morphological
      features like pore size, shape, and porous pattern in various diatoms isolated
      from Kurichi and Sulur fresh water lakes, Coimbatore, Tamil Nadu, India. Diatoms
      were identified as Nitzschia sp., Cyclotella meneghiniana, Coscinodiscus sp. and
      Cyclotella atomus based on their morphological features. The arrangement of
      porous nanostructures in these diatoms have been characterized. The change in the
      nanostructures present in the diatoms have been correlated to the contamination
      of water bodies. 

PMID- 26296231
TI  - Mitochondrial machineries for insertion of membrane proteins.
AB  - Mitochondria comprise two membrane systems, a bordering outer membrane and an
      invaginated inner membrane containing the oxidative phosphorylation machinery for
      ATP synthesis. Most mitochondrial membrane proteins are produced as precursors in
      the cytosolic compartment of the cell and imported into the organelle, whereas
      only few proteins are synthesized in the mitochondrial matrix. The topologically
      correct integration of hydrophobic precursor proteins into phospholipid bilayers
      is a particular challenge for protein translocation systems. Because of this
      mechanistic complexity, membrane proteins with distinct transmembrane topologies
      require profoundly different biogenesis pathways. Here we discuss recent findings
      on the structure and function of the diverse molecular machineries for
      mitochondrial membrane protein insertion. 

PMID- 26296233
TI  - Similarity analysis of functional connectivity with functional near-infrared
      spectroscopy.
AB  - One of the remaining challenges in functional connectivity (FC) studies is
      investigation of the temporal variability of FC networks. Recent studies focusing
      on the dynamic FC mostly use functional magnetic resonance imaging as an imaging
      tool to investigate the temporal variability of FC. We attempted to quantify this
      variability via analyzing the functional near-infrared spectroscopy (fNIRS)
      signals, which were recorded from the prefrontal cortex (PFC) of 12 healthy
      subjects during a Stroop test. Mutual information was used as a metric to
      determine functional connectivity between PFC regions. Two-dimensional
      correlation based similarity measure was used as a method to analyze within
      subject and intersubject consistency of FC maps and how they change in time. We
      found that within-subject consistency (0.61+/-0.09 ) is higher than intersubject
      consistency (0.28+/-0.13 ). Within-subject consistency was not found to be task
      specific. Results also revealed that there is a gradual change in FC patterns
      during a Stroop session for congruent and neutral conditions, where there is no
      such trend in the presence of an interference effect. In conclusion, we have
      demonstrated the between-subject, within-subject, and temporal variability of FC
      and the feasibility of using fNIRS for studying dynamic FC.

PMID- 26296234
TI  - Challenges in hemophilia care in Australia and New Zealand.
AB  - BACKGROUND: Health and life expectancy for people with hemophilia have improved
      significantly in recent years, but we face new challenges, especially in the
      context of resource-constrained health services. AIM: This paper aims to
      highlight such challenges and propose practical solutions. METHODS: Nine
      hemophilia specialists from Australia and New Zealand reached consensus on areas
      of greatest need for improvement in hemophilia care in these countries, based on
      clinical experience and published data, and agreed on how to address these.
      RESULTS: Demography, optimizing treatment and assessing treatment success were
      identified as broad areas of challenge which included: comorbidities in ageing
      patients; transitioning from pediatric to adult care; equity of care for remote
      populations; weight-based dosing in obese patients; tailoring prophylaxis;
      accurate diagnosis of acute joint pain; managing chronic arthropathy; providing
      psychosocial support; consistency in definitions and assessment; and quantifiable
      outcome measures. Practice points included increased cross-specialty coordination
      and including psychologists and rheumatologists as part of comprehensive care
      teams; close collaboration between pediatric and adult centers to facilitate
      transition of care; systems such as telehealth that ensure continuity of care for
      remote populations; using pharmacokinetic data to tailor therapy; rapid and
      accurate diagnosis of acute joint pain; using data from bleeding registries to
      assess treatment effects and help with service planning; and ensuring consistency
      through benchmarking and standardization of HTCs. SUMMARY: Achieving treatment
      equity, optimal outcomes and cost savings may be possible through investing in
      national governance structures, expanding the comprehensive model of care and
      implementing innovative solutions tailored to local needs.

PMID- 26296235
TI  - Venom Concentrations and Clotting Factor Levels in a Prospective Cohort of
      Russell's Viper Bites with Coagulopathy.
AB  - BACKGROUND: Russell's viper envenoming is a major problem in South Asia and
      causes venom induced consumption coagulopathy. This study aimed to investigate
      the kinetics and dynamics of venom and clotting function in Russell's viper
      envenoming. METHODOLOGY/PRINCIPAL FINDINGS: In a prospective cohort of 146
      patients with Russell's viper envenoming, we measured venom concentrations,
      international normalised ratio [INR], prothrombin time (PT), activated partial
      thromboplastin time (aPTT), coagulation factors I, II, V, VII, VIII, IX and X,
      and von Willebrand factor antigen. The median age was 39 y (16-82 y) and 111 were
      male. The median peak INR was 6.8 (interquartile range [IQR]: 3.7 to >13),
      associated with low fibrinogen [median,<0.01 g/L; IQR: <0.01-0.9 g/L), low factor
      V levels [median,<5%; IQR: <5-4%], low factor VIII levels [median,40%; IQR: 12
      79%] and low factor X levels [median, 48%; IQR: 29-67%]. There were smaller
      reductions in factors II, IX and VII over time. All factors recovered over 48 h
      post-antivenom. The median INR remained >3 at 6 h post-antivenom but had reduced
      to <2, by 24 h. The aPTT had also returned to close to normal (<50 sec) at 24 h.
      Factor VII, VIII and IX levels were unusually high pre-antivenom, median peak
      concentrations of 393%, 307% and 468% respectively. Pre-antivenom venom
      concentrations and the INR (r = 0.20, p = 0.02) and aPTT (r = 0.19, p = 0.03)
      were correlated (non-parametric Spearman analysis). CONCLUSIONS: Russell's viper
      coagulopathy results in prolonged aPTT, INR, low fibrinogen, factors V, VIII and
      X which recover over 48 h. Severity of clotting abnormalities was associated with
      venom concentrations.

PMID- 26296236
TI  - A New Test Unit for Disintegration End-Point Determination of Orodispersible
      Films.
AB  - No standard time or pharmacopoeia disintegration test method for orodispersible
      films (ODFs) exists. The USP disintegration test for tablets and capsules poses
      significant challenges for end-point determination when used for ODFs. We tested
      a newly developed disintegration test unit (DTU) against the USP disintegration
      test. The DTU is an accessory to the USP disintegration apparatus. It holds the
      ODF in a horizontal position, allowing top-view of the ODF during testing. A
      Gauge R&R study was conducted to assign relative contributions of the total
      variability from the operator, sample or the experimental set-up. Precision was
      compared using commercial ODF products in different media. Agreement between the
      two measurement methods was analysed. The DTU showed improved repeatability and
      reproducibility compared to the USP disintegration system with tighter standard
      deviations regardless of operator or medium. There is good agreement between the
      two methods, with the USP disintegration test giving generally longer
      disintegration times possibly due to difficulty in end-point determination. The
      DTU provided clear end-point determination and is suitable for quality control of
      ODFs during product developmental stage or manufacturing. This may facilitate the
      development of a standardized methodology for disintegration time determination
      of ODFs.

PMID- 26296237
TI  - The Question of Data Integrity in Article-Level Metrics.
AB  - Interest in and use of article-level metrics (ALMs) has grown rapidly amongst the
      research community, by researchers, publishers, funders, and research
      institutions. As this happens, it is critical to ensure secure and reliable data
      that is trustworthy and can be used by all. Two case studies are presented, which
      illustrate different approaches to establishing ALM data integrity. 

PMID- 26296238
TI  - Prognostic value of SYNTAX score based on coronary computed tomography
      angiography.
AB  - BACKGROUND: The long-term prognostic value of the computed tomography (CT)-based
      SYNTAX score has not yet been investigated. The aim of our study was to
      investigate the prognostic value of the CT-SYNTAX score in predicting major
      adverse cardiac events (MACEs) in populations who underwent both coronary
      computed tomography (CCTA) and invasive coronary angiography (ICA), compared with
      prognostic values of coronary artery disease (CAD) findings on CCTA and the ICA
      based SYNTAX score. METHODS: We retrospectively included 339 patients (213 men,
      mean age of 63.8+/-9.45years) with suspected CAD who underwent CCTA and ICA.
      SYNTAX score was obtained based on both CCTA and ICA. Follow-up clinical outcome
      data regarding composite MACEs were obtained. Cox proportional hazard models were
      developed to predict MACEs based on clinical variables, number of CAD vessels,
      and SYNTAX scores based on CCTA and ICA. The time-dependent receiver operating
      characteristic curve method was used, and the integrated area under the curve
      (iAUC) was calculated to compare the predictive prognosis of the models. RESULTS:
      During the median follow-up of 1374days, there were 30 MACEs. In multivariate Cox
      regression adjusted for clinical variables, SYNTAX score group 4 (>=33) on CCTA
      and SYNTAX score groups 3 (23-32) and 4 (>=33) on ICA showed increased hazard
      ratios for MACEs compared to SYNTAX score group 1 (0). CT-SYNTAX score
      demonstrated no significant difference in iAUC compared with ICA-SYNTAX score and
      the number of vessels of CAD on CCTA. CONCLUSIONS: CT-SYNTAX score can be a
      useful method for non-invasively predicting MACEs, especially in patients with
      complex CAD.

PMID- 26296239
TI  - Charge and spin transport in an organic molecular square.
AB  - Understanding electronic communication among multiple chromophoric and redox
      units requires construction of well-defined molecular architectures. Herein, we
      report the modular synthesis of a shape-persistent chiral organic square composed
      of four naphthalene-1,8:4,5-bis(dicarboximide) (NDI) sides and four trans-1,2
      cyclohexanediamine corners. Single crystal X-ray diffraction reveals some
      distortion of the cyclohexane chair conformation in the solid state. Analysis of
      the packing of the molecular squares reveals the formation of highly ordered, one
      dimensional tubular superstructures, held together by means of multiple
      [C?H???O?C] hydrogen-bonding interactions. Steady-state and time-resolved
      electronic spectroscopies show strong excited-state interactions in both the
      singlet and triplet manifolds. Electron paramagnetic resonance (EPR) and electron
      nuclear double resonance (ENDOR) spectroscopies on the monoreduced state reveal
      electron sharing between all four NDI subunits comprising the molecular square. 

PMID- 26296240
TI  - SERS encoded nanoparticle heterodimers for the ultrasensitive detection of folic
      acid.
AB  - In this paper, gold-silver nanoparticle (AuNP-AgNP) heterodimers were assembled
      with highly yield as an active SERS substrate, based on antigen-antibody
      immunoreaction. The developed SERS sensor has successful achieved the
      ultrasensitive detection of folic acid (FA) with the limit of detection (LOD) as
      0.86 pg/mL. And the linear range was from 0.005 ng/mL to 1 ng/mL. The results
      also demonstrated that this developed method showed high specificity and
      excellent recovery for the human serum samples, indicating its promising
      potential in bio-diagnosis and the environmental monitoring.

PMID- 26296241
TI  - EzyAmp signal amplification cascade enables isothermal detection of nucleic acid
      and protein targets.
AB  - Advancements in molecular biology have improved the ability to characterize
      disease-related nucleic acids and proteins. Recently, there has been an
      increasing desire for tests that can be performed outside of centralised
      laboratories. This study describes a novel isothermal signal amplification
      cascade called EzyAmp (enzymatic signal amplification) that is being developed
      for detection of targets at the point of care. EzyAmp exploits the ability of
      some restriction endonucleases to cleave substrates containing nicks within their
      recognition sites. EzyAmp uses two oligonucleotide duplexes (partial complexes 1
      and 2) which are initially cleavage-resistant as they lack a complete recognition
      site. The recognition site of partial complex 1 can be completed by hybridization
      of a triggering oligonucleotide (Driver Fragment 1) that is generated by a target
      specific initiation event. Binding of Driver Fragment 1 generates a completed
      complex 1, which upon cleavage, releases Driver Fragment 2. In turn, binding of
      Driver Fragment 2 to partial complex 2 creates completed complex 2 which when
      cleaved releases additional Driver Fragment 1. Each cleavage event separates
      fluorophore quencher pairs resulting in an increase in fluorescence. At this
      stage a cascade of signal production becomes independent of further target
      specific initiation events. This study demonstrated that the EzyAmp cascade can
      facilitate detection and quantification of nucleic acid targets with sensitivity
      down to aM concentration. Further, the same cascade detected VEGF protein with a
      sensitivity of 20nM showing that this universal method for amplifying signal may
      be linked to the detection of different types of analytes in an isothermal
      format. 

PMID- 26296242
TI  - A portable system for on-site quantification of formaldehyde in air based on G
      quadruplex halves coupled with A smartphone reader.
AB  - A portable colorimetric determination system based on G-quadruplex DNAzyme
      integrated with a smartphone was developed to quantitatively detect formaldehyde
      (FA). The method is based on the oxidation of FA by H2O2, which prevents the 2,2'
      azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS)-H2O2 reaction catalyzed
      by G-quadruplex halves. With the addition of FA, the amount of the blue-green
      colored free-radical cation (ABTS+) was reduced. The concentration of FA can be
      determined by monitoring this competitive reaction with a UV-vis spectrometer.
      Response surface methodology (RSM) and Box-Behnken design (BBD) were applied for
      optimization of the colorimetric assay. A smartphone-based colorimetric reader
      was also developed, which could display FA responses and report the concentration
      in real-time. The system could detect FA as low as 0.01 uM with a linear range of
      1-600 uM. Taking advantages of smartphone and DNAzyme, the assay provides great
      potential for its practical application as a home testing or on-site analysis
      with high sensitivity and selectivity.

PMID- 26296244
TI  - Thermal cycling can extend tool life in orthopaedic operating rooms.
AB  - Thermal cycling is a temperature modulation process developed to improve the
      performance, durability and longevity of materials. This process has been
      successfully utilized in the automotive, aeronautic and manufacturing industries.
      Surgical cutting tools undergo cyclical loading and generally fail by dulling,
      suggesting that thermal cycling may improve their performance and longevity. Ten
      2.5 mm orthopaedic drill bits were randomized, with five undergoing thermal
      cycling within their sterile packaging and five serving as untreated controls.
      Using a servohydraulic testing machine, 100 drilling cycles were performed with
      each drill bit into the diaphyseal region of bovine femurs. After every 25
      cycles, data was collected by performing identical drilling cycles into simulated
      human cortical bone material. Maximum force, maximum normalized torque and
      drilling work were measured, and a scanning electron microscope was used to
      measure outer corner wear. After 100 drilling cycles, the maximum drilling force,
      maximum normalized torque, drilling work and microscopic outer corner wear were
      all significantly lower for the treated drill bits (p < 0.05). Thermal cycling
      has the potential to decrease operating room costs and thermal necrosis
      associated with dull cutting tools. Application of this technology may also be
      relevant to surgical cutting tools such as saw blades, burrs and reamers.

PMID- 26296243
TI  - Astrocyte-expressed FABP7 regulates dendritic morphology and excitatory synaptic
      function of cortical neurons.
AB  - Fatty acid binding protein 7 (FABP7) expressed by astrocytes in developing and
      mature brains is involved in uptake and transportation of fatty acids, signal
      transduction, and gene transcription. Fabp7 knockout (Fabp7 KO) mice show
      behavioral phenotypes reminiscent of human neuropsychiatric disorders such as
      schizophrenia. However, direct evidence showing how FABP7 deficiency in
      astrocytes leads to altered brain function is lacking. Here, we examined neuronal
      dendritic morphology and synaptic plasticity in medial prefrontal cortex (mPFC)
      of Fabp7 KO mice and in primary cortical neuronal cultures. Golgi staining of
      cortical pyramidal neurons in Fabp7 KO mice revealed aberrant dendritic
      morphology and decreased spine density compared with those in wild-type (WT)
      mice. Aberrant dendritic morphology was also observed in primary cortical neurons
      co-cultured with FABP7-deficient astrocytes and neurons cultured in Fabp7 KO
      astrocyte-conditioned medium. Excitatory synapse number was decreased in mPFC of
      Fabp7 KO mice and in neurons co-cultured with Fabp7 KO astrocytes. Accordingly,
      whole-cell voltage-clamp recording in brain slices from pyramidal cells in the
      mPFC showed that both amplitude and frequency of action potential-independent
      miniature excitatory postsynaptic currents (mEPSCs) were decreased in Fabp7 KO
      mice. Moreover, transplantation of WT astrocytes into the mPFC of Fabp7 KO mice
      partially attenuated behavioral impairments. Collectively, these results suggest
      that astrocytic FABP7 is important for dendritic arbor growth, neuronal
      excitatory synapse formation, and synaptic transmission, and provide new insights
      linking FABP7, lipid homeostasis, and neuropsychiatric disorders, leading to
      novel therapeutic interventions.

PMID- 26296245
TI  - Foundations of Pharmacotherapy for Heart Failure With Reduced Ejection Fraction:
      Evidence Meets Practice, Part I.
AB  - Pharmacologic treatment for systolic heart failure, otherwise known as heart
      failure with reduced ejection fraction, has been established through clinical
      trials and is formulated into guidelines to standardize the diagnosis and
      treatment. The premise of pharmacologic therapy in heart failure with reduced
      ejection fraction is aimed primarily at interrupting the neurohormonal cascade
      that is responsible for altering left ventricular shape and function. This is the
      first in a series of articles to describe the pharmacologic agents in the
      guidelines that impact the morbidity and mortality associated with heart failure.
      Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and
      vasodilators will be presented in the context of the mechanism of action in heart
      failure, investigational trials that showed beneficial effects, and the practical
      application for clinical use. 

PMID- 26296246
TI  - Self-reported Adherence to a Low-Sodium Diet and Health Outcomes in Patients With
      Heart Failure.
AB  - BACKGROUND: Most clinicians rely on patients' self-report of following a low
      sodium diet to determine adherence of patients with heart failure (HF). Whether
      self-reported adherence to a low-sodium diet is associated with cardiac event
      free survival is unclear. PURPOSES: To determine (1) whether self-reported is
      concordant with adherence to a low-sodium diet measured by food diaries and 24
      hour urinary sodium excretion and (2) whether self-reported adherence to a low
      sodium diet predicts cardiac event-free survival. METHODS: Adherence to a low
      sodium diet was measured using 3 measures in 119 HF patients: (1) self-reported
      adherence, 1 item from the Self-care of Heart Failure Index scale; (2) a 3-day
      food diary; (3) 24-hour urinary sodium excretion. Patients were followed up for a
      median of 297 days to determine cardiac hospitalization or emergency department
      visit. One-way analysis of variance and Cox regression were used to address our
      purposes. RESULTS: Self-reported adherence was concordant with adherence to a low
      sodium diet measured by food diaries and 24-hour urinary sodium excretion. Thirty
      one patients who reported they always follow a low-sodium diet had an average
      sodium intake less than 3 g/d (F = 5.07, P = .002) and 3.3 g of a mean 24-hour
      urinary sodium excretion (F = 3.393, P = .020). Patients who reported they never
      or rarely follow a low-sodium diet had 4.7 times greater risk of having cardiac
      events than did those who always followed a low-sodium diet (P = .017).
      CONCLUSION: Self-reported adherence to a low-sodium diet predicted cardiac event
      free survival demonstrating clinicians can use this as an indicator of adherence.

PMID- 26296247
TI  - Adolescents With Congenital Heart Disease and Their Parents: Needs Before
      Transfer to Adult Care.
AB  - BACKGROUND: Patients with congenital heart disease (CHD) are in need of lifelong
      healthcare. For adolescents with CHD, this transfer to adult-care clinic can be
      difficult. OBJECTIVE: The aim was to identify and describe the needs of
      adolescents with CHD and their parents during the transition before transfer to
      adult cardiologic healthcare. METHODS: This study has an exploratory design with
      a qualitative approach, where 13 adolescents with CHD and their parents (n = 12)
      were individually interviewed. The interviews were analyzed with content
      analysis. RESULTS: The analysis of the adolescents' interviews resulted in 3
      categories: change of relationships, knowledge and information, and daily living.
      The theme that emerged depicting the meaning of the categories found was Safety
      and control, indicating needs of continuity, knowledge, and taking
      responsibility. Analysis of the parents' answers gave 2 categories: change of
      relationship and daily living. The theme that emerged was safety and trust,
      indicating needs of continuity and shifting responsibility. CONCLUSIONS: The
      transition must be carefully planned to ensure that adolescents can master new
      skills to manage the transfer to adult cardiologic healthcare. A structured
      program may facilitate and fulfill the needs of the adolescents and their
      parents, taking into consideration the aspects of trust, safety, and control.
      However, the content and performance of such a program must also be examined. We
      plan to undertake an extensive research project in the area, and this study will
      be a baseline for further research.

PMID- 26296248
TI  - The effects of fat layer on temperature distribution during microwave atrial
      fibrillation catheter ablation.
AB  - To investigate the effects of fat layer on the temperature distribution during
      microwave atrial fibrillation catheter ablation in the conditions of different
      ablation time; 3D finite element models (fat layer and no fat layer) were built,
      and temperature distribution was obtained based on coupled electromagnetic
      thermal analysis at 2.45 GHz and 30 W of microwave power. Results shown: in the
      endocardial ablation, the existence of the fat layer did not affect the shape of
      the 50  degrees C contour before 30 s. The increase speed of depth became quite
      slowly in the model with fat layer after 30 s. When ablation depth needed fixed,
      there are no significant effect on effectively ablation depth whether fat layer
      over or not. However, the existence of fat layer makes the temperature lower in
      the myocardium, and maximum temperature point closer to the myocardium surface.
      What is more, in the model with fat layer, effective ablation reach lower maximum
      temperature and the shallower depth of 50  degrees C contour. But there are
      larger ablation axial length and transverse width. In this case, doctor should
      ensure safety of normal cardiac tissue around the target tissue. In the
      epicardial ablation, the existence of fat layer seriously affects result of the
      microwave ablation. The epicardial ablation needs more heating time to create
      lesion. But epicardial ablation can be better controlled in the shape of
      effective ablation area because of the slowly increase of target variables after
      the appearing of 50  degrees C contour. Doctor can choose endocardial or
      epicardial ablation in different case of clinic requirement. 

PMID- 26296250
TI  - Development of molecular photoswitch with very fast photoresponse based on
      asymmetrical bis-azospiropyran.
AB  - To study the effects of an extended bis-azo conjugated bridge with two different
      photochemical functions on a molecule in photochromic responses, a novel
      asymmetrical bifunctional bis-azo spiropyran photochromic dye was designed and
      synthesized. The obtained photoresponses were compared with symmetrical
      bifunctional bis-azo spiropyran analogues, and relative mono-azo and simple
      spiropyrans. Colourimetric behaviour, luminescence, and switching kinetics of all
      the dyes were studied. The largest molar absorption coefficient in merocyanine
      form, quickest response to light, and highest fluorescence quantum yield of the
      spiropyran form with a superior ratio of emission intensities of spiropyran to
      merocyanine form were achieved for the asymmetric bis-azospiropyran.
      Solvatochromic effect was studied to observe the solvent effects on non
      irradiation colouration of the photochromic dyes. Furthermore, The molecular
      energy levels for optimized geometries of the synthesized bis-azospiropyrans and
      their probable photochemical products were obtained at the B3LYP/6-31G(d) level
      of theory. 

PMID- 26296249
TI  - Effectiveness of beta-thalassemia prenatal diagnosis in Southern Iran: a cohort
      study.
AB  - AIM: The aim of this study was to evaluate the effectiveness of prenatal
      diagnosis (PND) for the prevention of thalassemia in Southern Iran. METHODS: From
      2004 to 2012 1346 couples with beta-thalassemia minor were referred to our
      center. Mutation analyses utilized different methods including polymerase chain
      reaction-based technique of amplification refractory mutation system (ARMS),
      Restriction Fragment Length Polymorphism Analysis of PCR-Amplified Fragments (PCR
      RFLP) and Gel Electrophoresis and direct sequencing. Haplotype analysis of the
      beta-globin gene cluster was done routinely using the PCR-RFLP technique.
      RESULTS: Of the 1346 couples, 884 (66%) requested PND. They had a total of 985
      pregnancies (954 singleton and 31 twin pregnancies): the 1016 fetuses underwent
      chorionic villus sampling (CVS). Thalassemia major was diagnosed in 266 cases
      (26.2%), and termination of pregnancy was requested by the parents in 264 of them
      (99%). Thalassemia trait was detected in 499 (49.1%) and 251 cases (24.7%) showed
      no beta-thalassemia mutations. There were three misdiagnoses (0.4%) (affected
      children diagnosed as carriers at PND). A unique pattern of thalassemia mutations
      was present in the study population, with IVS II-I (G->A), C36-37(-T), IVS I
      5(G>C), -25bpdel (252-276), IVS I-110(G>A) and C44 (-C) being present in 62% of
      cases. CONCLUSION: The pattern of distribution of thalassemia mutations differs
      among ethnic groups within the same country.

PMID- 26296251
TI  - Evaluation of chemical components and properties of the jujube fruit using near
      infrared spectroscopy and chemometrics.
AB  - Near-infrared spectroscopy (NIRS) calibrations were developed for the
      discrimination of spectra of the jujube (Zizyphus jujuba Mill.) fruit samples
      from four geographical regions. Prediction models were developed for the
      quantitative prediction of the contents of jujube fruit, i.e., total sugar, total
      acid, total phenolic content, and total antioxidant activity. Four pattern
      recognition methods, principal component analysis (PCA), linear discriminant
      analysis (LDA), least squares-support vector machines (LS-SVM), and back
      propagation-artificial neural networks (BP-ANN), were used for the geographical
      origin classification. Furthermore, three multivariate calibration models based
      on the standard normal variate (SNV) pretreated NIR spectroscopy, partial least
      squares (PLS), BP-ANN, and LS-SVM were constructed for quantitative analysis of
      the four analytes described above. PCA provided a useful qualitative plot of the
      four types of NIR spectra from the fruit. The LS-SVM model produced best
      quantitative prediction results. Thus, NIR spectroscopy in conjunction with
      chemometrics, is a very useful and rapid technique for the discrimination of
      jujube fruit. 

PMID- 26296252
TI  - Prediction of P-branch emission spectral lines of NaF and 63Cu35Cl molecules.
AB  - The analytical formula derived by Sun et al. in 2011 and used to predict the
      rotational lines for rovibrational diatomic systems is improved in this study.
      The new formula is obtained by adding a higher order spectral term Hupsilon that
      is neglected in our previous expression. A physical requirement is also added to
      the converging process to minimize the possible error of the predicted rotational
      line. All these are applied to study some rovibrational transition systems of
      (63)Cu(35)Cl and NaF molecules. The results indicate that the accuracy of the P
      branch rotational lines predicted by this new formula is about one order of
      magnitude better than the results obtained using the previous formula, and that
      both the small Hupsilon contribution and the improved converging requirement may
      play a vital role in predicting the high-lying rovibrational energies and the
      rotational lines. Comparisons between physical predictions and mathematical
      extrapolations on the rotational lines are also given. 

PMID- 26296253
TI  - Development of methodology for identification the nature of the polyphenolic
      extracts by FTIR associated with multivariate analysis.
AB  - Tannins are polyphenolic compounds of complex structures formed by secondary
      metabolism in several plants. These polyphenolic compounds have different
      applications, such as drugs, anti-corrosion agents, flocculants, and tanning
      agents. This study analyses six different type of polyphenolic extracts by
      Fourier transform infrared spectroscopy (FTIR) combined with multivariate
      analysis. Through both principal component analysis (PCA) and hierarchical
      cluster analysis (HCA), we observed well-defined separation between condensed
      (quebracho and black wattle) and hydrolysable (valonea, chestnut, myrobalan, and
      tara) tannins. For hydrolysable tannins, it was also possible to observe the
      formation of two different subgroups between samples of chestnut and valonea and
      between samples of tara and myrobalan. Among all samples analysed, the chestnut
      and valonea showed the greatest similarity, indicating that these extracts
      contain equivalent chemical compositions and structure and, therefore, similar
      properties. 

PMID- 26296254
TI  - A DFT study of infrared spectra and Monte Carlo predictions of the solvation
      shell of Praziquantel and beta-cyclodextrin inclusion complex in liquid water.
AB  - In this paper, we report a theoretical study of the inclusion complexes of
      Praziquantel (PZQ) and beta-cyclodextrin (beta-CD) in liquid water. The starting
      geometry has been carried out by molecular mechanics simulations, and afterwards
      optimized in B3LYP level with a 6-311G(d) basis set. Monte Carlo simulations have
      been used to calculate the solvation shell of the PZQ/beta-CD inclusion
      complexes. Moreover, the vibrational frequencies and the infrared intensities for
      the PZQ/beta-CD complex were computed using the B3LYP method. It is demonstrated
      that this combined model can yield well-converged thermodynamic data even for a
      modest number of sample configurations, which makes the methodology particularly
      adequate for understanding the solute-solvent interaction used for generating the
      liquid structures of one solute surrounded by solvent molecules. The complex
      solvation shell showed an increase of the water molecule level in relation to the
      isolated PZQ molecule because of the hydrophilic effect of the CD molecule. The
      infrared spectra showed that the contribution that originated in the PZQ molecule
      was not predominant in the upper-wave number region in the drug/beta-CD. The
      movement that purely originated in the PZQ molecule was localized in the
      absorption band, ranging from 1328 to 1688cm(-1). 

PMID- 26296255
TI  - Insights on a Giant Aneurysm Treated Endovascularly.
AB  - Background Endovascular treatment with stent-assisted Guglielmi detachable coils
      is an accepted method for treating intracranial giant aneurysms that otherwise
      would require more invasive or destructive treatment or could not be treated at
      all. Nevertheless, there is a paucity of information concerning inner postcoiling
      aneurysmal changes in human subjects over the long term. We report a postmortem
      analysis of a patient with a giant aneurysm at the vertebrobasilar junction (VBJ)
      who was treated endovascularly and studied pathologically 24 months after
      treatment. Materials and Method The head was removed at autopsy and prefixed in a
      10% neutral buffered formalin solution. The brain was gently removed from the
      skull base after cutting the intracranial nerves and vascular structures. The
      giant VBJ aneurysm and its relationship with the brainstem, cranial nerves, and
      vessels were captured photographically and analyzed. Afterward, under operating
      microscope guidance, the vertebrobasilar system with the aneurysm was gently and
      carefully detached from the brainstem and carefully analyzed. Results No complete
      fibrous obliteration of the aneurysm lumen could be detected in our case, and no
      endothelialization had taken place 24 months after treatment. Conclusions Our
      findings agree with those of previous similar reports. Coiling, in particular in
      large or giant aneurysms, may be burdened by the risk of coil compaction and
      recanalization, but it has the advantage of not affecting the flow in the
      perforating arteries. 

PMID- 26296256
TI  - Correction: Binding of Superantigen Toxins into the CD28 Homodimer Interface Is
      Essential for Induction of Cytokine Genes That Mediate Lethal Shock.

PMID- 26296257
TI  - Peer Reviewers and Publishers of Scholarly Book Get Subpoenas in Lawsuit against
      Chemical Companies.
AB  - Lawyers representing more than 20 chemical companies took the unusual step of
      issuing subpoenas to five peer reviewers of a scholarly book as part of
      litigation over the alleged health risks of a widely used chemical compound. The
      peer reviewers, who are historians and health experts, were summoned to be
      questioned in the case, which pits a former chemical worker who now suffers from
      cancer against the companies, including the Dow Chemical Company, the Goodrich
      Corporation, the Goodyear Tire & Rubber Company, the Monsanto Company, and
      Uniroyal Inc. The book's publishers also received subpoenas, several months
      earlier, to provide information about early drafts of the book and its peer
      review. 

PMID- 26296259
TI  - Outcomes After Referral for Acute Inpatient Rehabilitation in Hospitalized
      Patients With Cancer.

PMID- 26296258
TI  - The development of a questionnaire measure of diabetes-related distress in
      Chinese-speaking patients: the Diabetes-Related Distress Questionnaire (DRDQ).
AB  - PURPOSE: To develop and evaluate the reliability and validity of a Diabetes
      Related Distress Questionnaire for Chinese-speaking patients with diabetes.
      METHODS: The Diabetes-Related Distress Questionnaire (DRDQ) included 11 quality
      of-life questions translated from a Diabetes, Attitudes, Wishes, and Needs study
      and four native items developed by researchers based on patients' experiences. A
      sample of 981 Chinese-speaking patients with diabetes in Taiwan was invited to
      complete the questionnaire. RESULTS: A minimum of 4.2 % of patients used each
      response option for each item. Exploratory factor analysis suggested a two-factor
      structure, representing treatment-related distress (factor 1) and progression
      related distress (factor 2). The mean loading of items on their corresponding
      factor was high (0.60), while the mean loading on the other factor was low
      (0.10). A confirmatory factor analysis confirmed a single structure of the DRDQ
      (root-mean-square error of approximation = 0.063, comparative fit index = 0.93).
      The Cronbach's alpha was 0.89 for the DRDQ scale, 0.87 for the factor 1, and 0.68
      for the factor 2. As expected, people with insulin-treated and HbA1c > 7 %
      reported significantly greater negative scores than their counterparts on the
      total score and all items of the DRDQ, with the exception of item 2. A moderate
      effect size was demonstrated between insulin known groups (ranging from 0.14 to
      0.46) and between HbA1c known groups (ranging from 0.08 to 0.87). CONCLUSIONS:
      The DRDQ is a psychometrically sound instrument that can be used to assess
      diabetes-related distress in Chinese-speaking patients in Taiwan.

PMID- 26296260
TI  - A Mother's Last Illness and Death-Lessons Learned by a Physician Daughter.

PMID- 26296261
TI  - Interdisciplinary Palliative Care for Patients With Lung Cancer.
AB  - CONTEXT: Palliative care, including symptom management and attention to quality
      of life (QOL) concerns, should be addressed throughout the trajectory of a
      serious illness such as lung cancer. OBJECTIVES: This study tested the
      effectiveness of an interdisciplinary palliative care intervention for patients
      with Stage I-IV non-small cell lung cancer (NSCLC). METHODS: Patients undergoing
      treatments for NSCLC were enrolled in a prospective, quasi-experimental study
      whereby the usual care group was accrued first followed by the intervention
      group. Patients in the intervention group were presented at interdisciplinary
      care meetings, and appropriate supportive care referrals were made. They also
      received four educational sessions. In both groups, QOL, symptoms, and
      psychological distress were assessed at baseline and 12 weeks using surveys which
      included the Functional Assessment of Cancer Therapy-Lung and the Lung Cancer
      Subscale, the 12-item Functional Assessment of Chronic Illness Therapy-Spiritual
      Well-Being, and the Distress Thermometer. RESULTS: A total of 491 patients were
      included in the primary analysis. Patients who received the intervention had
      significantly better scores for QOL (109.1 vs. 101.4; P < 0.001), symptoms (25.8
      vs. 23.9; P < 0.001) spiritual well-being (38.1 vs. 36.2; P = 0.001), and lower
      psychological distress (2.2 vs. 3.3; P < 0.001) at 12 weeks, after controlling
      for baseline scores, compared to patients in the usual care group. Patients in
      the intervention group also had significantly higher numbers of completed advance
      care directives (44% vs. 9%; P < 0.001), and overall supportive care referrals
      (61% vs. 28%; P < 0.001). The benefits were seen primarily in the earlier stage
      patients vs. those with Stage IV disease. CONCLUSION: Interdisciplinary
      palliative care in the ambulatory care setting resulted in significant
      improvements in QOL, symptoms, and distress for NSCLC patients.

PMID- 26296262
TI  - Statins and the risk of pancreatic cancer in Type 2 diabetic patients--A
      population-based cohort study.
AB  - The aim of this study was to determine whether statin use exerts a protective
      effect against pancreatic cancer in Type 2 diabetic patients. A retrospective
      population-based cohort study was designed to analyze the National Health
      Insurance Research database (NHIRD) from 1997-2010 in Taiwan. A total of
      1,140,617 patients with a first-time diagnosis of Type 2 diabetes were enrolled.
      The event was defined as newly diagnosed pancreatic cancer. A Cox proportional
      hazards regression model with time-dependent covariates was used to calculate
      hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of pancreatic
      cancer associated with statin use in the diabetic cohort. A total of 2,341
      patients with newly diagnosed pancreatic cancer were identified in the diabetic
      cohort during the follow-up period of 6,968,217.1 person-years. In this cohort,
      450,282 patients were defined as statin users (statin use >= 28 cumulative
      defined daily dose [cDDD] in 1 year) and 0.14% had pancreatic cancer; 690,335
      patients were statin nonusers (statin use <28 cDDD in 1 year) and 0.25% had
      pancreatic cancer. Statin use significantly decreased the risk of pancreatic
      cancer (adjusted HRs: 0.78 in 28-83 cDDD per year; 0.48 in 84-180 cDDD per year;
      and 0.33 in >180 cDDD per year) after adjusting for multiple confounders. There
      was a significant dose-effect of statin use for the risk of pancreatic cancer (p
      for trend: <0.001). Statin use may be associated with a reduced risk of
      pancreatic cancer in Type 2 diabetic patients. More research is needed to clarify
      this association.

PMID- 26296263
TI  - Prostate cancer detection: the effect of obesity on Asian men.

PMID- 26296264
TI  - Interleukin-6 as an emerging regulator of renal cell cancer.
AB  - BACKGROUND: Our knowledge on the molecular basis of kidney cancer metastasisis
      still relatively low. About 25-30% of patients suffering from clear cell renal
      cell carcinoma (ccRCC)present metastatic disease at the time of primary
      diagnosis. Only 10% of patients diagnosed with stage IV disease survive 5 years
      and 20-50% of patients diagnosed with localized tumor develop metastases within 3
      years. High mortality of patients with this cancer is associated with a large
      potential for metastasis and resistance to oncologic treatments such as chemo-
      and radiotherapy. Literature data based on studies conducted on other types of
      cancers suggest that in metastatic ccRCC, the complex of interleukin-6 (IL-6) and
      its soluble receptor (sIL-6R; complex IL-6/sIL-6R) and the signal transduction
      pathway (gp130/STAT3) might play a key role in this process. PURPOSE: Therefore,
      in this review we focus on the role of IL-6 and its signaling pathways as a
      factor for development and spread of RCC. Analyzing the molecular basis of cancer
      spreading will enable the development of prognostic tests, evaluate individual
      predisposition for metastasis, and produce drugs that target metastases. As the
      development of effective systemic treatments evolve from advancements in
      molecular biology, continued studies directed at understanding the genetic and
      molecular complexities of this disease are critical to improve RCC treatment
      options.

PMID- 26296265
TI  - No changes in serum tryptase after bariatric surgery.

PMID- 26296267
TI  - Comparison of web versus interview participants in a case-control study.
AB  - PURPOSE: To evaluate whether selection bias might be introduced because of
      differential self-selection into an internet-based case-control study. METHODS:
      We compared sociodemographic factors and behavioral factors for cases and
      controls who opted for their first entree into the study be via the internet (Web
      group) versus the telephone (Phone group), using data from a study on clubfoot.
      RESULTS: Overall, 200 of 1,825 mothers were in the Web group and were more likely
      to be non-Hispanic White, nonsmokers, more educated, wealthier, and took >=7
      medications/vitamins in pregnancy. These differences were greater for case
      mothers, introducing the potential for selection bias. Maternal smoking is an
      established risk factor for clubfoot and was confirmed in the Phone group (OR =
      1.61) but was not observed in the Web group (OR = 1.15). CONCLUSION: Our results
      suggest there is potential for selection bias if enrollment is solely internet
      based for a case-control study.

PMID- 26296266
TI  - Change in waist circumference with longer time in the United States among
      Hispanic and Chinese immigrants: the modifying role of the neighborhood built
      environment.
AB  - PURPOSE: We examined whether living in neighborhoods supportive of healthier
      diets and more active lifestyles may buffer immigrants against the unhealthy
      weight gain that is purported to occur with longer length of US residence.
      METHODS: Neighborhood data referring to a 1-mile buffer around participants'
      baseline home addresses were linked to longitudinal data from 877 Hispanic and
      684 Chinese immigrants aged 45 to 84 years in the Multi-Ethnic Study of
      Atherosclerosis. We used ethnicity-stratified linear mixed models to examine
      whether food and activity-based neighborhood measures (healthy food stores,
      walkability, and recreational facilities) were associated with change in waist
      circumference (WC) over a 9-year follow-up. RESULTS: Among Hispanics, living in
      neighborhoods with more resources for healthy food and recreational activity was
      related to lower baseline WC. However, there was no association with change in WC
      over time. Among Chinese, living in more walkable neighborhoods was associated
      with lower baseline WC and with slower increases in WC over time, especially
      among the most recent immigrant arrivals. CONCLUSIONS: Where immigrants reside
      may have implications for health patterns that emerge with longer time in the
      United States.

PMID- 26296268
TI  - National Analysis of Short-Term Outcomes After Pulmonary Resections on
      Cardiopulmonary Bypass.
AB  - BACKGROUND: Pulmonary resections using cardiopulmonary bypass (CPB) are
      infrequently performed. Their short-term outcomes are not well described. We
      queried the National Inpatient Sample over a 10-year period (2001 to 2011) to
      more clearly delineate the short-term outcomes of patients undergoing pulmonary
      resections on CPB. METHODS: We identified all patients 18 years and older who
      underwent pulmonary lobectomy (LB) or pneumonectomy (PN) on CPB; lung
      transplantations were excluded. We then grouped these patients based on the
      setting in which bypass was used: LB/PN with planned CPB (group 1), LB/PN with
      concomitant on-pump cardiac procedure (group 2), or LB/PN requiring CPB secondary
      to injury (group 3). Demographic data and inhospital outcomes were obtained for
      each patient. RESULTS: In all, 843 patients underwent LB or PN on CPB during the
      study period. Lobectomies were the most commonly performed procedure overall.
      Inhospital mortality for groups 1, 2, and 3 were 22% (n = 58), 16% (n = 61), and
      57% (n = 115), respectively. Complications were prevalent across all groups.
      Routine discharge was achieved by fewer than half of all patients: 48% of group 1
      (n = 128); 34% of group 2 (n = 129); and 18% of group 3 (n = 36). Pneumonectomy
      (odds ratio 2.74, 95% confidence interval: 1.00 to 7.53, p = 0.049) as well as
      using CPB either as part of a combined cardiac surgery (odds ratio 1.48, 95%
      confidence interval: 0.39 to 5.59, p = 0.002) or because of injury (odds ratio
      6.52, 95% confidence interval: 2.13 to 19.99, p = 0.002) were found to be
      significant multivariate predictors of short-term mortality. CONCLUSIONS:
      Pulmonary resections on CPB carry considerable short-term mortality and
      morbidity, but some risk can be partially mitigated when bypass is planned
      preoperatively.

PMID- 26296269
TI  - Long-Term Venovenous Extracorporeal Membrane Oxygenation Support for Acute
      Respiratory Distress Syndrome.
AB  - BACKGROUND: Given substantial advances in venovenous extracorporeal membrane
      oxygenation (ECMO) technology, long-term support is increasingly feasible.
      Although the benefits of short-term ECMO as a bridge to recovery in acute
      respiratory distress syndrome (ARDS) are well described, the utility and outcomes
      of long-term support remain unclear. METHODS: Patients requiring ECMO for ARDS
      between January 2009 and November 2012 were retrospectively reviewed and analyzed
      separately for those requiring ECMO support for less than 3 weeks or for 3 weeks
      or longer. Demographic factors, ECMO variables, and outcomes were assessed.
      RESULTS: Fifty-five patients with ARDS received ECMO during the study period,
      with 11 patients requiring long-term ECMO support and a median duration of 36
      (interquartile range: 24 to 68) days. Recovery was the initial goal in all
      patients. Pre-ECMO mechanical ventilatory support, indices of disease severity,
      and the ECMO cannulation strategy were similar between the two groups. Eight
      (73%) patients receiving long-term support were bridged to recovery, and 1
      patient was bridged to transplantation after a refractory course. Eight (73%)
      patients receiving long-term support and 25 (57%) patients receiving short-term
      support survived to 30 days and hospital discharge. CONCLUSIONS: Previously, long
      term ECMO support was thought to be associated with unfavorable outcomes. This
      study, however, may provide support for the efficacy of ECMO support even for 3
      weeks or more as a bridge to recovery or transplantation.

PMID- 26296270
TI  - Class III Obesity is Not a Contraindication to Venovenous Extracorporeal Membrane
      Oxygenation Support.
AB  - BACKGROUND: The use of venovenous extracorporeal membrane oxygenation (ECMO) has
      increased as a bridge to recovery for acute respiratory distress syndrome (ARDS)
      refractory to conventional support. Morbid obesity can pose a significant
      challenge to obtaining indexed flows, and outcomes in this population are not
      well described. METHODS: Patients requiring ECMO for ARDS between January 2009
      and November 2012 were retrospectively reviewed. Demographics, ECMO variables,
      and outcomes were assessed. Morbid obesity and super obesity were defined as a
      body mass index (BMI) greater than 40 kg/m(2) and greater than 50 kg/m(2),
      respectively. RESULTS: Fifty-five patients with ARDS were placed on ECMO during
      the study period. Twelve were morbidly obese with a BMI of 49.0 kg/m(2)
      (interquartile range [IQR]: 45.4-57.3 kg/m(2)). Pre-ECMO mechanical ventilatory
      support and indices of disease severity were similar between the 2 groups, as
      were cannulation strategy and duration of ECMO support. Nine (75%) morbidly obese
      patients and 27 (63%) non-morbidly obese patients were successfully weaned from
      ECMO support, and patient survival to time of discharge was 67% and 58%,
      respectively. In the subset of super obese patients (n = 6; BMI, 57.3 kg/m(2)
      [IQR: 51.3-66.5 kg/m(2)]), recovery and midterm survival was 100%. CONCLUSIONS:
      In this review, class III obesity was not associated with poorer outcomes, and
      based on these data, ECMO support should not be withheld from this patient
      population.

PMID- 26296271
TI  - Idiopathic Subglottic Stenosis: Factors Affecting Outcome After Single-Stage
      Repair.
AB  - BACKGROUND: Idiopathic subglottic stenosis is a rare inflammatory condition
      affecting the subglottic larynx. We have treated 263 patients (only 2 were male)
      with this condition. The purpose of this study is to determine factors affecting
      outcome and predisposing to complications. METHODS: Information was gathered from
      chart reviews, surveys, and a prospective database. RESULTS: Median time from
      diagnosis to surgery was 24 months. Antinuclear antibodies when measured were
      positive in 76 patients (47%). Prior tracheal procedures were done in 58 patients
      (22%), and 184 patients (70%) had prior endoscopic procedures. Resection of the
      posterior cricoid mucosa with tracheal membranous wall flap was done in 150
      patients (57%). Tailored cricoplasty was performed in 105 patients (40%).
      Extubation in the operating room was achieved in 247 patients (94%). Steroid
      therapy for edema was required in 63 patients (24%). Anastomotic complications
      occurred in 30 patients, 17 granulations and 7 subcutaneous air. Twenty-three
      patients (8.7%) have recurrence (14 mild, 9 recalcitrant) requiring dilation.
      Risk factors for anastomotic complications and recurrence were edema requiring
      steroids, use of mitomycin C, and prior tracheostomy, stents, and vocal cord
      involvement. Follow-up was available for 227 patients. Follow-up survey of 180
      patients revealed, on a 10-point scale, effectiveness 9.4, satisfaction 9.4, and
      symptom improvement 9.4. A normal voice was present in 82 patients (45%); 96
      patients (54%) had change in voice; and 121 patients (67%) had difficulty
      projecting their voice. CONCLUSIONS: Single-stage reconstructive surgery resulted
      in 96% good-to-excellent results. Recalcitrant stenosis developed in 4% of
      patients. Stents, postoperative edema, mitomycin use, and vocal cord involvement
      are risks for recurrence. Recurrence was related to reactivation of disease in 14
      patients and to technical problems in 6 patients.

PMID- 26296272
TI  - The Expanding Role of Endoscopic Robotics in Mitral Valve Surgery: 1,257
      Consecutive Procedures.
AB  - BACKGROUND: The role of robotic instruments in mitral valve (MV) surgery
      continues to evolve. The purpose of this study was to assess the safety,
      efficacy, and scope of MV surgery using a lateral endoscopic approach with
      robotics (LEAR) technique. METHODS: From 2006 to 2013, a dedicated LEAR team
      performed 1,257 consecutive isolated MV procedures with or without tricuspid
      valve repair or atrial ablation. The procedures were performed robotically
      through five right-side chest ports with femoral artery or ascending aortic
      perfusion and balloon occlusion. Operative videos and data were recorded on all
      procedures and reviewed retrospectively. RESULTS: The mean age of all patients
      was 59.3 +/- 20.5 years, and 8.4% (n = 105) had previous cardiac surgery. The MV
      repair was performed in 1,167 patients (93%). The MV replacement was performed in
      88 patients (7%), and paravalvular leak repair in 2 patients. Concomitant atrial
      ablation was performed in 226 patients (18%), and tricuspid valve repair in 138
      patients (11%). Operative mortality occurred in 11 patients (0.9%) and stroke in
      9 patients (0.7%). Predischarge echocardiograms demonstrated mild or less mitral
      regurgitation in 98.3% of MV repair patients. At mean follow-up of 50 +/- 26
      months, 44 patients (3.8%) required MV reoperation. Application of the LEAR
      technique to all institutional isolated MV procedures increased from 46% in the
      first year to more than 90% in the last 3 years. CONCLUSIONS: Mitral valve repair
      or replacement, including concomitant procedures, can be performed safely and
      effectively using the LEAR technique. With a dedicated robotic team, the vast
      majority of patients with MV disorders, either isolated or with concomitant
      problems, can be treated using the LEAR technique.

PMID- 26296273
TI  - Nadir Hematocrit on Bypass and Rates of Acute Kidney Injury: Does Sex Matter?
AB  - BACKGROUND: Reports have associated nadir hematocrit (Hct) on cardiopulmonary
      bypass with the occurrence of renal dysfunction. Recent literature has suggested
      that women, although more often exposed to lower nadir Hct, have a lower risk of
      postoperative renal dysfunction. We assessed whether this relationship held
      across a large multicenter registry. METHODS: We undertook a prospective,
      observational study of 15,221 nondialysis-dependent patients (10,376 male, 68.2%;
      4,845 female, 31.8%) undergoing cardiac surgery between 2010 and 2014 across 26
      institutions in Michigan. We calculated crude and adjusted OR between nadir Hct
      during cardiopulmonary bypass and stage 2 or 3 acute kidney injury (AKI), and
      tested the interaction of sex and nadir Hct. The predicted probability of AKI was
      plotted separately for men and women. RESULTS: Nadir Hct less than 21% occurred
      among 16.6% of patients, although less commonly among men (9.5%) than women
      (31.9%; p < 0.001). Acute kidney injury occurred among 2.7% of patients, with
      small absolute differences between men and women (2.6% versus 3.0%, p = 0.20).
      There was a significant interaction between sex and nadir Hct (p = 0.009). The
      effect of nadir Hct on AKI was stronger among male patients (adjusted odds ratio
      per 1 unit decrease in nadir Hct 1.10, 95% confidence interval: 1.05 to 1.13)
      than female patients (adjusted odds ratio 1.01, 95% CI: 0.96, 1.06). CONCLUSIONS:
      Lower nadir Hct was associated with an increased risk of AKI, and the effect
      appears to be stronger among men than women. Understanding of the mechanism
      underlying this association remains uncertain, although these results suggest the
      need to limit exposure to lower nadir Hct, especially for male patients.

PMID- 26296274
TI  - Intensity-modulated radiation therapy versus 2D-RT or 3D-CRT for the treatment of
      nasopharyngeal carcinoma: A systematic review and meta-analysis.
AB  - OBJECTIVE: To compare clinical treatment outcomes and late toxicities of
      intensity-modulated radiation therapy (IMRT) with those obtained with two
      dimensional radiation therapy (2D-RT) or three-dimensional conformal radiation
      therapy (3D-CRT) in nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: We
      searched all the eligible studies from the Cochrane Library, PubMed, Medline, and
      Embase. The meta-analysis was performed to compare odds ratio (OR) for overall
      survival (OS), tumor local control (LC), and late toxicities. RESULTS: A total of
      eight studies met the criteria to perform a meta-analysis including 3570
      participants, with 1541 patients in the IMRT group and 2029 in the 2D-RT or 3D
      CRT group. The IMRT group was associated with a better 5-year overall survival
      (OR=1.51; 95% confidence interval (CI) 1.23-1.87; p=0.0001), and tumor local
      control (LC) (OR=1.94; 95% CI 1.53-2.46; p<0.00001). According to CTCAE v3.0
      (Common Terminology Criteria for Adverse Events) and RTOG/EORTC (Radiation
      Therapy Oncology Group/European Organisation for Research and Treatment of
      Cancer), the incidence of late xerostomia in those who received IMRT was
      significantly lower than that of the control group (OR=0.18; 95% CI, 0.07-0.46;
      p=0.0004). In addition, the radiation-induced chronic toxicities rate of trismus
      and temporal lobe neuropathy (TLN) were also significantly lower in the IMRT
      group than in the control group (OR=0.18; 95% CI 0.04-0.83; p=0.03; OR=0.44; 95%
      CI 0.28-0.69; p=0.0003, respectively). CONCLUSIONS: This systematic review and
      meta-analysis demonstrated that IMRT mayobtain a better antitumor effect, and
      significantly decrease the incidence of radiation-induced late toxicities in
      patients with NPC.

PMID- 26296275
TI  - [Diagnosis and management of ankyloglossia in young children].
AB  - Ankyloglossia is a common condition. Its prevalence is between 3.2% and 4.8%
      depending on the series and is largely underestimated given the fact of non
      diagnosis when the symptoms are limited. It is defined as a short lingual
      frenulum resulting in a limitation of the lingual mobility. It is due to a defect
      in cellular apoptosis embryogenesis between the floor of the mouth and tongue.
      The result is a fibrous and short lingual frenulum. Several classifications were
      used to make the diagnosis. However, these are the clinical implications,
      particularly on food and primarily breastfeeding in the baby and phonation in
      older children that will motivate the management. This is surgical and different
      techniques are available: infants before the age of 6 months and when the lingual
      frenulum is still a fine cellular membrane, frenotomy is recommended. Frenectomy
      with or without frenoplasty is indicated for the older child. The surgery is
      simple, the results are good and rapidly improving grievances. Complications are
      rare. Finally, speech therapy is important when there are implications for
      phonation. 

PMID- 26296276
TI  - [Not Available].

PMID- 26296277
TI  - [Head and neck superficial venous malformations].
AB  - Management of vascular malformations and vascular tumors has recently been
      maximized by the establishment of an accurate clinical and histological
      classification and by the development of multidisciplinary expert consultations.
      Head and neck localizations of venous malformations are common, thus maxillo
      facial surgeons should be aware of the characteristics of this pathology and the
      principles of its management. Diagnosis is mainly clinical and must be certified
      by Doppler-ultrasonography and contrast enhanced magnetic resonance imaging with
      T2 fat-saturation sequence. Therapeutic decision depends on the volume of the
      lesion, and on functional, cosmetic and psychological complaints. Sclerotherapy
      is now the preferred treatment of head and neck venous malformations. It is
      performed in specialized interventional radiology units by intralesional
      injections of sclerosing solution under fluoroscopic guidance. Surgery is useful
      in some cases, either on its own or following sclerotherapy. In case of bulky
      lesion, it is necessary to search for and prevent a severe coagulopathy before
      planning any intervention. 

PMID- 26296278
TI  - Liquid biopsy in cancer.

PMID- 26296279
TI  - ONCO-TESE: Obtaining spermatozoa after radical orchiectomy for testicular tumour
      and azoospermia.
AB  - OBJECTIVE: There is the possibility of diagnosing azoospermia in cases of
      testicular tumours in patients who wish to preserve fertility. Our objective is
      to present a technique for obtaining spermatozoa from testicles with ex vivo
      tumours in order to preserve fertility in these patients. MATERIAL AND METHODS: A
      34-year-old patient was referred for azoospermia. The physical examination
      revealed a node in the lower pole of the left testicle. In the scrotal
      ultrasound, the testicle presented disperse microcalcifications and a 1-cm
      hypoechoic mass in the lower pole. The tumour markers were negative, and the CT
      showed no distant disease. Left radical orchiectomy was performed, along with the
      placement of a testis prosthesis. Bench surgery was then performed, with
      extraction of the seminiferous tubules in the upper pole. RESULTS: Of the
      submitted samples, 4 progressive and 1 nonprogressive motile spermatozoa were
      identified per field. Two samples were cryopreserved. The pathological report
      indicated the presence of a seminoma measuring 1.3 * 1 cm, with free margins and
      with no invasion of the rete testis (stage I). An assisted reproduction technique
      (intracytoplasmic sperm injection) was performed on the patient's partner with
      the frozen spermatozoa, which resulted in pregnancy and the subsequent birth of a
      healthy child. CONCLUSION: We propose this technique as the method of choice for
      obtaining spermatozoa from patients who simultaneously present azoospermia and
      testicular tumours and who wish to preserve their fertility.

PMID- 26296280
TI  - Adverse cognitive effects of antiepileptic pharmacotherapy: Each additional drug
      matters.
AB  - The study was set up to evaluate the impact of the total drug load of
      antiepileptic pharmacotherapy on cognition. Retrospective analyses were based on
      834 patients with epilepsy who underwent a brief routine assessment of executive
      function and verbal memory (EpiTrack Plus) at our department. The total drug load
      was quantified in two ways: (1) number of concurrent antiepileptic drugs (AEDs)
      and (2) total drug load according to the defined daily dose (DDD) provided by the
      World Health Organization. The cognitive measures showed higher inverse
      correlations with the number of AEDs (executive function: r=-0.35, p<0.001;
      memory: r=-0.22, p<0.001) than with the total DDD (executive function: r=-0.27,
      p<0.001; memory: r=-0.17, p<0.001). Reanalysis with statistical control for
      disease severity hardly changed the aforementioned results. With each additional
      drug in polytherapy, we observed a significantly lower performance in executive
      function. In this regard an additional explorative approach revealed that
      regimens combining AEDs with favorable cognitive profiles were associated with
      higher cognitive performance. Correlations between indicators of disease severity
      and drug load indices were low: altogether explaining only up to 9% of the
      observed variance in drug load. The findings demonstrate a considerable adverse
      effect of a higher drug load on cognition, especially on executive functions.
      Simply counting the number of drugs may be sufficient as a rough estimate of the
      risk of side effects. However, the combination of AEDs with favorable cognitive
      profiles may attenuate the negative effect of the total drug load. 

PMID- 26296281
TI  - Creatinine kinase isoenzyme-MB: A simple prognostic biomarker in patients with
      pulmonary embolism treated with thrombolytic therapy.
AB  - BACKGROUND: Creatinine kinase isoenzyme-MB (CK-MB) is a biomarker for detecting
      myocardial injury. The aim of this study was to evaluate the association between
      admission CK-MB levels and in-hospital and long-term clinical outcomes in
      pulmonary embolism (PE) patients treated with thrombolytic tissue-plasminogen
      activator. METHODS: A total of 148 acute PE patients treated with tissue
      plasminogen activator enrolled in the study. The study population was divided
      into 2 tertiles, based on admission CK-MB levels. The high CK-MB group (n=35) was
      defined as having a CK-MB level in the third tertile (>31.5 U/L), and the low
      group (n=113) was defined as having a level in the lower 2 tertiles (<=31.5 U/L).
      RESULTS: High CK-MB group had a higher incidence of in-hospital mortality (37.1%
      vs 1.7%, P<.001). Admission systolic blood pressure and tricuspid annular plane
      systolic excursion were lower in the high CK-MB group. In the receiver-operating
      characteristic curve analysis, a CK-MB value of more than 31.5 U/L yielded a
      sensitivity of 86.7% and specificity of 83.5% for predicting in-hospital
      mortality. During long-term follow-up, recurrent PE, major and minor bleeding,
      and mortality rates were similar in both groups. CONCLUSION: Creatinine kinase
      isoenzyme-MB is a simple, widely available, and useful biomarker for predicting
      adverse in-hospital clinical outcomes in PE.

PMID- 26296282
TI  - Sleep apnea and atrial fibrillation in coronary artery bypass grafting patients-
      also a part of the OSAFED syndrome?

PMID- 26296284
TI  - Practical mechanical threshold estimation in rodents using von Frey hairs/Semmes
      Weinstein monofilaments: Towards a rational method.
AB  - Here, we reconsider the status quo in testing mechanical sensitivity with von
      Frey's hairs. The aim is to improve paw withdrawal estimates by integrating
      current psychometric theory, and to maximise the clinical relevance and
      statistical power of mechanosensory models. A wealth of research into human
      tactile stimulus perception may be extended to the quantification of laboratory
      animal behaviour. We start by reviewing each step of the test, from its design
      and application through to data analysis. Filament range is assessed as a whole;
      possible test designs are compared; techniques of filament application to mice
      and rats are considered; curve fitting software is introduced; possibilities for
      data pooling and curve fitting are evaluated. A rational update of classical
      methods in line with recent advances in psychometrics and supported by open
      source software is expected to improve data homogeneity, and Reduce and Refine
      animal use in accord with the '3R' principles. 

PMID- 26296285
TI  - Optimization and pharmacological validation of a set-shifting procedure for
      assessing executive function in rats.
AB  - BACKGROUND: Set-shifting tests represent a reliable paradigm to assess executive
      functions in humans and animals. In the rat, set-shifting in a cross-maze is a
      recognized method. In this test, rats must learn an egocentric rule to locate
      food reinforcement. Once acquired, a second rule, based on visual-cue strategy,
      allows the location of the food. Ability of rats to shift from the first to the
      second rule is considered to reflect cognitive flexibility. NEW METHOD: This
      study aimed at optimizing the most currently used set-shifting protocol in a
      cross-maze for standardized drug testing by modulating the parameters related to
      caloric restriction, reward preference, and by redefining the notion of turn bias
      and classification of errors sub-types, i.e. perseverative vs. regressive. The
      new protocol has then been used to assess rats treated by sub-chronic
      phencyclidine administration and investigate the potential reversal effect of
      tolcapone, a brain penetrant catechol-O-methyl transferase inhibitor. RESULTS:
      The new procedure resulted in a decreased total duration and a re-definition of
      turn bias and error subtypes. Despite preferences for sweet rewards, caloric
      restriction had to be maintained to motivate animals. Overall, sub-chronic PCP
      treated rats made mostly perseverative errors compared to controls and required
      more trials to shift between the two rules. Tolcapone partly reversed impairments
      observed in PCP-treated rats. CONCLUSION: The new protocol has improved the
      reliability of key parameters and has contributed to the decrease of the test
      duration. PCP-treated rats submitted to this protocol have been shown to have
      significant deficits that could be reversed by tolcapone.

PMID- 26296287
TI  - Design, development and metrological characterization of a low capacity precision
      industrial force transducer.
AB  - The paper discusses the development of the ring shaped force transducers for
      measurement of force in lower capacity to meet the industrial requirements with
      the increasing technological developments. A 50 N ring shaped force transducer
      for tension mode has been developed by studying the analytical and computational
      methods. The force transducer developed has been metrologically studied according
      to the calibration procedure based on the standard ISO 376 and uncertainty of
      measurement of the force transducer is found to be+/-0.10% (k=2), while taking
      into account the relative uncertainty contribution due to necessary factors like
      repeatability, reproducibility, zero offset, interpolation, resolution and
      reversibility. The force transducer developed may further be studied for
      improvement of metrological performance and may suitably be developed for other
      lower capacities like 10 N, 20 N etc. The force transducer developed offers very
      economical alternative of complex shaped force transducers with simple design and
      manufacturing features. The force transducer developed may be proved very helpful
      in providing traceability to the user industries and calibration laboratories in
      the lower range of force measurement and serve as force transfer standard.

PMID- 26296286
TI  - Strategies for optical control and simultaneous electrical readout of extended
      cortical circuits.
AB  - BACKGROUND: To dissect the intricate workings of neural circuits, it is essential
      to gain precise control over subsets of neurons while retaining the ability to
      monitor larger-scale circuit dynamics. This requires the ability to both evoke
      and record neural activity simultaneously with high spatial and temporal
      resolution. NEW METHOD: In this paper we present approaches that address this
      need by combining micro-electrocorticography (MUECoG) with optogenetics in ways
      that avoid photovoltaic artifacts. RESULTS: We demonstrate that variations of
      this approach are broadly applicable across three commonly studied mammalian
      species - mouse, rat, and macaque monkey - and that the recorded MUECoG signal
      shows complex spectral and spatio-temporal patterns in response to optical
      stimulation. COMPARISON WITH EXISTING METHODS: While optogenetics provides the
      ability to excite or inhibit neural subpopulations in a targeted fashion, large
      scale recording of resulting neural activity remains challenging. Recent advances
      in optical physiology, such as genetically encoded Ca(2+) indicators, are
      promising but currently do not allow simultaneous recordings from extended
      cortical areas due to limitations in optical imaging hardware. CONCLUSIONS: We
      demonstrate techniques for the large-scale simultaneous interrogation of cortical
      circuits in three commonly used mammalian species.

PMID- 26296288
TI  - Downregulation of the Musca domestica peptidoglycan recognition protein SC (PGRP
      SC) leads to overexpression of antimicrobial peptides and tardy pupation.
AB  - PGRP (peptidoglycan recognition protein) is a conserved protein family that
      recognizes the peptidoglycan in bacterial cell wall and causes the activation of
      various innate immune responses. Previous studies have reported that PGRP-SCs in
      Drosophila dampen the activation of Immune Deficiency (Imd) pathway to microbial
      infection, and participate in the lifespan extension of the insects. To
      facilitate understanding the function of PGRP-SCs from an evolutionary angle, we
      identified and functionally characterized the PGRP-SC gene in the housefly Musca
      domestica, a species that has adapted to a septic environment much harsher than
      the natural habitat of Drosophila. The gene designated as MdPGRP-SC was found
      most abundantly expressed in the 3rd instar larvae, and is expressed at this
      developmental stage predominantly in the gut. MdPGRP-SC was virtually unchanged
      in whole larvae after a septic injury at the second larval instar, while two
      antimicrobial peptides (AMPs), diptericin and attacin, were upregulated in the
      first 24h but not later. Through dsRNA microinjection, MdPGRP-SC was knocked down
      by RNA interference (RNAi), and caused the significant increased expression of
      diptericin and attacin. The pupation of MdPGRP-SC-depleted larvae was severely
      suppressed compared to controls. Opposite to the expression trend of MdPGRP-SC, a
      spontaneous active expression of diptericin and attacin was found in pre-pupae
      but not in third instar larvae. Taken together, our study reveals that
      downregulation of MdPGRP-SC leads to the overexpression of the AMPs, and is
      involved in the larvae-to-pupa transition of housefly. 

PMID- 26296289
TI  - miR-223 is upregulated in monocytes from patients with tuberculosis and regulates
      function of monocyte-derived macrophages.
AB  - Tuberculosis (TB) is a serious infectious disease that most commonly affects the
      lungs. Macrophages are among the first line defenders against establishment of
      Mycobacterium tuberculosis infection in the lungs. In this study, we found that
      activation and cytokine production in monocyte-derived macrophages (MDM) from
      patients with active TB was impaired. miR-223 expression was significantly
      elevated in monocytes and MDM from patients with TB compared with healthy
      controls. To determine the functional role of miR-223 in macrophages, stable miR
      223-expressing and miR-223 antisense-expressing U937 cells were established.
      Compared with empty vector controls, expression of IL-1beta, IL-6, TNF-alpha and
      IL-12p40 genes was significantly higher in miR-223 antisense-expressing U937
      cells, but lower in miR-223-expressing U937 cells. miR-223 can negatively
      regulate activation of NF-kappaB by inhibition of p65 phosphorylation and nuclear
      translocation. It is concluded that miR-223 can regulate macrophage function by
      inhibition of cytokine production and NF-kappaB activation. 

PMID- 26296291
TI  - Recurrent intraneural ganglion cysts: Pathoanatomic patterns and treatment
      implications.
AB  - The etiology of intraneural ganglion cysts has been poorly understood. This has
      resulted in the development of multiple surgical treatment strategies and a high
      recurrence rate. We sought to analyze these recurrences in order to provide a
      pathoanatomic explanation and staging classification for intraneural cyst
      recurrence. An expanded literature search was performed to identify frequencies
      and patterns in cases of intraneural ganglion cyst recurrences following primary
      surgery. Two univariate analyses were completed to identify associations between
      the type of revision surgery and repeat cyst recurrences. The expanded literature
      search found an 11% recurrence rate following primary surgery, including 64
      recurrences following isolated cyst decompression (Group 1); six after articular
      branch resection (Group 2); and none following surgical procedures that addressed
      the joint (Group 3). Eight cases did not specify the type of primary surgery. In
      group 1, forty-eight of the recurrences (75%) were in the parent nerve, three
      involved only the articular branch, and one travelled along the articular branch
      in a different distal direction without involving the main parent nerve. In group
      2, only one case (17%) recurred/persisted within the parent nerve, one recurred
      within a persistent articular branch, and one formed within a persistent
      articular branch and travelled in a different distal direction. Intraneural
      recurrences most commonly occur following surgical procedures that only target
      the main parent nerve. We provide proven or theoretical explanations for all
      identified cases of intraneural recurrences for an occult or persistent articular
      branch pathway.

PMID- 26296290
TI  - Imbalance Between Th17 Cells and Regulatory T Cells During Monophasic
      Experimental Autoimmune Uveitis.
AB  - The aim of this study is to explore the dynamic changes in IL-17-expressing T
      cells (Th17)/Treg expression in monophasic experimental autoimmune uveitis
      (mEAU). mEAU was induced in Lewis rats with IRBP1177-1191 peptide and evaluated
      clinically and pathologically on days 9, 13, 18, 23, 28, 35, and 48. Lymphocytes
      isolated from inguinal lymph nodes were subjected to flow cytometry to analyze
      the frequency of Th17/Treg cells. The levels of cytokines (IL-17, IL-6, IL-10,
      transforming growth factor (TGF)-beta) in serum were detected by enzyme-linked
      immunosorbent assay (ELISA). Real-time quantitative PCR (RT-PCR) was used for
      measuring the levels of IL-17, IL-6, TGF-beta, and Foxp3. Clinical and
      histopathologic assessment showed that mEAU began on day 9, peaked on day 13, and
      decreased to normal on day 18. The frequency of Th17 cells increased obviously on
      day 9, peaking on day 13, while the frequency of Treg cells increased on day 13,
      peaked on day 18, and remained at a high level until day 48. In the serum, the
      levels of IL-17 and IL-6 peaked on day 9 and gradually decreased to normal on day
      28. The level of TGF-beta increased on day 9, peaked on day 13, and decreased to
      normal on day 35. Meanwhile, the level of IL-10 increased on day 9 and stayed at
      a high level until day 48. Additionally, the above results were further confirmed
      by RT-PCR. The imbalance between Th17 and Treg cells contributes to the onset and
      progression of mEAU, and a compartmental imbalance of Treg over Th17 exists in
      the recovery phase of mEAU. 

PMID- 26296292
TI  - Mechanism of adrenocortical toxicity induced by quinocetone and its bidesoxy
      quinocetone metabolite in porcine adrenocortical cells in vitro.
AB  - Quinocetone (QCT) is a new feeding antibacterial agent in the QdNOs family. The
      mechanism of its adrenal toxicity is far from clear. This study was conducted to
      estimate the adrenal cell damage induced by QCT and its bidesoxy-quinocetone (B
      QCT) metabolite and to further investigate their mechanisms. Following doses of
      QCT increasing from 5 to 50 MUM, cell apoptosis and necrosis, mitochondrial
      dysfunction and redox imbalance were observed in porcine adrenocortical cells.
      The mRNA levels of the six components of intermediary enzymes and the adrenal
      renin-angiotensin-aldosterone system (RAAS) displayed a dysregulation induced by
      QCT, indicating that QCT might influence aldosterone secretion not only through
      the upstream of the production but also through the downstream of the adrenal
      RAAS pathway. In contrast, B-QCT had few toxic effects on the cell apoptosis,
      mitochondrial dysfunction and redox imbalance. Moreover, LCMS-IT-TOF analysis
      showed that no desoxy metabolites of QCT were found in either cell lysate or
      supernatant samples. In conclusion, we reported on the cytotoxicity in porcine
      adrenocortical cells exposed to QCT via oxidative stress, which raised awareness
      that its toxic effects resulted from N->O groups, and its toxic mechanism might
      involve the interference of the steroid hormone biosynthesis pathway.

PMID- 26296293
TI  - Addressing overtreatment of screen detected DCIS; the LORIS trial.
AB  - Overdiagnosis, and thus overtreatment, are inevitable consequences of most
      screening programmes; identification of ways of minimising the impact of
      overdiagnosis demands new prospective research, in particular the need to
      separate clinically relevant lesions that require active treatment from those
      that can be safely left alone or monitored and only need treated if they change
      characteristics. Breast cancer screening has led to a large increase in ductal
      carcinoma in situ (DCIS) diagnoses. This is a widely heterogeneous disease and
      most DCIS detected through screening is of high cytonuclear grade and therefore
      likely to be important clinically. However, the historic practice of surgical
      treatment for all DCIS is unlikely to be optimal for lower risk patients. A
      clearer understanding of how to manage DCIS is required. This article describes
      the background and development of 'The low risk' DCIS trial (LORIS), a phase III
      trial of surgery versus active monitoring. LORIS will determine if it is
      appropriate to manage women with screen detected or asymptomatic, low grade and
      intermediate grade DCIS with low grade features, by active monitoring rather than
      by surgical treatment.

PMID- 26296294
TI  - Reaching women who do not participate in the regular cervical cancer screening
      programme by offering self-sampling kits: a systematic review and meta-analysis
      of randomised trials.
AB  - INTRODUCTION: Population coverage for cervical cancer screening is an important
      determinant explaining differences in the incidence of cervical cancer between
      countries. Offering devices for self-sampling has the potential to increase
      participation of hard-to-reach women. METHODS: A systematic review and meta
      analysis were performed to evaluate the participation after an invitation
      including a self-sampling device (self-sampling arm) versus an invitation to have
      a sample taken by a health professional (control arm), sent to under-screened
      women. RESULTS: Sixteen randomised studies were found eligible. In an intention
      to-treat analysis, the pooled participation in the self-sampling arm was 23.6%
      (95% confidence interval (CI)=20.2-27.3%), when self-sampling kits were sent by
      mail to all women, versus 10.3% (95% CI=6.2-15.2%) in the control arm
      (participation difference: 12.6% [95% CI=9.3-15.9]). When women had to opt-in to
      receive the self-sampling device, as used in three studies, the pooled
      participation was not higher in the self-sampling compared to the control arm
      (participation difference: 0.2% [95% CI=-4.5-4.9%]). CONCLUSION: An increased
      participation was observed in the self-sampling arm compared to the control arm,
      if self-sampling kits were sent directly to women at their home address. However,
      the size of the effect varied substantially among studies. Since participation
      was similar in both arms when women had to opt-in, future studies are warranted
      to discern opt-in scenarios that are most acceptable to women.

PMID- 26296295
TI  - A phase I study of daily afatinib, an irreversible ErbB family blocker, in
      combination with weekly paclitaxel in patients with advanced solid tumours.
AB  - BACKGROUND: This phase I study evaluated afatinib, an irreversible ErbB family
      blocker, plus paclitaxel in patients with advanced solid tumours likely to
      express human epidermal growth factor receptor (HER1/EGFR) or HER2. METHODS: Oral
      afatinib was combined with intravenous paclitaxel (80mg/m(2); days 1, 8 and 15
      every four weeks) starting at 20mg once daily and escalated to 40 and 50mg in
      successive cohorts of ?3 patients. The primary objective was to determine the
      maximum tolerated dose (MTD) of afatinib combined with paclitaxel. Secondary
      objectives included safety, pharmacokinetics and antitumour activity. RESULTS:
      Sixteen patients were treated. Dose-limiting toxicities with afatinib 50mg were
      fatigue and mucositis. The MTD was determined as afatinib 40mg with paclitaxel
      80mg/m(2), which proved tolerable with repeated dosing. Frequent adverse events
      (AEs) included diarrhoea (94%), fatigue (81%), rash/acne (81%), decreased
      appetite (69%) and inflammation of mucosal membranes (69%); no grade 4 treatment
      related AEs were observed. Five (31%) confirmed partial responses were observed
      in patients with non-small cell lung cancer (n=3), oesophageal cancer and
      cholangiocarcinoma; eight (50%) patients remained on study for ?6months.
      Pharmacokinetic parameters of afatinib and paclitaxel were similar for single
      administration or in combination. CONCLUSIONS: The MTD and recommended phase II
      dose of once-daily afatinib combined with paclitaxel 80mg/m(2) (days 1, 8 and 15
      every four weeks) was 40mg. AEs at or below this dose were generally manageable
      with repeated dosing. No pharmacokinetic interactions were observed. This
      combination demonstrated promising antitumour activity. TRIAL REGISTRATION:
      ClinicalTrials.gov, NCT00809133.

PMID- 26296296
TI  - Ultraviolet radiation after exposure to a low-fluence IPL home-use device: a
      randomized clinical trial.
AB  - The prevailing advice is to avoid sun exposure after intense pulsed light (IPL)
      hair removal. However, no systematic evaluation of ultraviolet radiation (UVR)
      after IPL hair removal exits. Therefore, we investigated the occurrence of side
      effects in subjects receiving solar-simulated UVR after a low-fluence IPL
      treatment with a home-use device. Sixteen subjects with Fitzpatrick skin types
      (FST) II-V were enrolled. Three constitutive buttock blocks (4.4 * 6.4 cm) were
      each subdivided into four sites, randomized to one IPL exposure of 0, 7, 8, or 10
      J/cm2 (spectral output 530-1100 nm). Blocks were randomized to no UVR or three
      standard erythema doses (SEDs) UVR either 30 min or 24 h after IPL. Follow-up
      visits were 48 h, 1 week, and 4 weeks after IPL. Outcome measures were (i)
      clinical skin reactions, (ii) reflectance measurements of erythema and
      pigmentation, and (iii) pain. Subjects with FST II-IV experienced no skin
      reactions up to 4 weeks after IPL, neither erythema, edema, blisters, crusting,
      textual, nor pigment changes. Reflectance confirmed no change in erythema and
      pigmentation (p >= 0.090). UVR exposure induced erythema and increased
      pigmentation. The combination of IPL and UVR induced skin reactions not different
      to responses from UVR (IPL-UVR vs. UVR, p >= 0.164). Pain was generally low
      (median 1, range 0-4) and correlated positively with fluence and pigmentation
      (Spearman's rho >= 0.394, p < 0.001). One subject with FST V experienced
      perifollicular hyperpigmentation after IPL and slightly more intense when exposed
      to UVR. A single UVR exposure of three SEDs either shortly or 1 day after low
      fluence IPL causes no amplification of skin responses in constitutive skin of
      individuals with FST II-IV.

PMID- 26296297
TI  - Hematin loses its membranotropic activity upon oligomerization into malaria
      pigment.
AB  - Malaria is an infectious disease caused by Plasmodium type parasites transmitted
      by the bites of infected female anopheles mosquitoes. The malaria parasite
      multiplies in red blood cells where it degrades hemoglobin. This degradation of
      hemoglobin proteins releases hematin, an iron-containing porphyrin, which
      provokes membrane disruption and lysis. The malaria parasite blocks hematin
      induced lysis by biocrystallization, a process that converts hematin into
      insoluble and chemically inert crystals. Hematin molecules are especially prone
      to self-assembly as dimers, oligomers and aggregates depending on environmental
      conditions (pH, solvent, temperature, concentration, ionic strength). Considering
      the different forms of hematin-based assemblies, it is still unclear which are
      the ones able to interact with membranes. We have prepared hematin under
      different conditions to form hematin-based assemblies and to measure their
      ability to interact and to disorganize membranes. Our results show that different
      forms of hematin molecules are able to penetrate lipid membranes. Interestingly,
      this membrane activity is spontaneously inhibited at acidic pH and it can be
      restored under neutral pH. By contrast, the oligomers of beta-hematin were found
      to be completely harmless toward lipid membranes. Finally, the AFM visualization
      of hematin interaction with supported lipid bilayers showed for the first time
      its preferential interaction with defaults in membranes, at the boundaries
      between two distinct lipid phases. The superficial adsorption of aggregates on
      membranes and the absence of effect due to oligomers were also confirmed with
      AFM. 

PMID- 26296298
TI  - Uterine exteriorization compared with in situ repair for Cesarean delivery: a
      systematic review and meta-analysis.
AB  - PURPOSE: To compare perioperative outcomes following uterine exteriorization vs
      in situ repair after Cesarean delivery. SOURCE: We searched CENTRAL, MEDLINE(r),
      EMBASETM, CINAHL, and ClinicalTrials.gov for randomized clinical trials that
      included any of our primary outcomes (blood loss, intraoperative nausea,
      vomiting, and pain), or secondary outcomes. PRINCIPAL FINDINGS: Sixteen studies
      were included. In total, 9,736 subjects underwent exteriorization, 9,703 had in
      situ uterine repair. Estimated blood loss was not statistically different between
      the two methods of uterine repair (mean difference [MD], -61.03 mL; 95%
      confidence interval [CI], -127.34 to 5.28); however, exteriorization reduced the
      decrease in hemoglobin (MD, -0.14 g.dL(-1); 95% CI, -0.22 to -0.07). Estimated
      blood loss was reduced with exteriorization in a sensitivity analysis that
      excluded an outlier study. There was no statistically significant difference in
      intraoperative nausea (odds ratio [OR], 0.99; 95% CI, 0.74 to 1.34), vomiting
      (OR, 0.94; 95% CI, 0.66 to 1.35), or pain (OR, 1.52; 95% CI, 0.86 to 2.71)
      between the two repair techniques. In situ repair was associated with faster
      return of bowel function (MD, 3.09 hr; 95% CI, 2.21 to 3.97). An association
      between exteriorization and endometritis did not reach statistical significance
      (OR, 1.25; 95% CI, 0.96 to 1.62). CONCLUSION: Uterine repair by exteriorization
      may reduce blood loss and the associated decrease in hemoglobin, but the
      difference may not be clinically relevant. There was no statistically significant
      difference between the two repair techniques for intraoperative nausea, vomiting,
      or pain. In situ repair may be associated with a faster return of bowel function.

PMID- 26296299
TI  - One-year outcome of the sevoflurane in acute myocardial infarction randomized
      trial.
AB  - BACKGROUND: Sevoflurane is an inhalation anesthetic that has cardioprotective
      effects. There is limited information regarding its use outside of the operating
      room and its potential protective effect for patients presenting with myocardial
      infarction. METHODS: In the Sevoflurane In Acute Myocardial Infarction trial,
      patients with a first acute ST-elevation myocardial infarction (STEMI) who were
      treated by primary percutaneous coronary intervention were randomized to
      inhalation of sevoflurane or oxygen (control). From the time of the patient's
      arrival for cardiac catheterization, the anesthesia team administered sevoflurane
      or oxygen for 30 min using a tight-fitting mask. In this substudy, we report the
      one-year outcomes. Patients were followed clinically for one year; they underwent
      a thallium cardiac viability study at six months and an echocardiogram at one
      year. RESULTS: Forty-six patients completed follow-up. One patient in the
      sevoflurane group died. The mean [standard deviation (SD)] ejection fraction by
      single-photon emission computed tomography at six months was 51.7 (7.7)% in the
      sevoflurane group and 51 (9.1)% in the control group (mean difference, 0.7%; 95%
      confidence interval [CI], -5.9 to 7.3; P = 0.831). The median [interquartile
      range] amount of scarring at six months was 0% [0 - 8] in the sevoflurane group
      and 2.5% [0 - 7.1] in control group (mean difference, -0.1%; 95% CI, -4.6 to 4.4;
      P = 0.700). The mean (SD) percentage of hibernating myocardium was similar in
      both groups 0% [0, 5] (mean difference, -1.3%; 95% CI, -3.4 to 0.9; P = 0.259).
      The mean (SD) ejection fraction at one year increased compared with baseline by
      8.0 (9.1)% (P < 0.001). CONCLUSIONS: In this study, we did not find an effect of
      sevoflurane on left ventricular function or myocardial injury at one year post
      STEMI. This trial was registered at www.clinicaltrials.gov ; identifier:
      NCT00971607.

PMID- 26296300
TI  - Efficacy of palonosetron for preventing postoperative nausea and vomiting: a
      systematic review and meta-analysis.
AB  - PURPOSE: Palonosetron, a second-generation 5-hydroxytryptamine 3 receptor
      antagonist (5-HT3RA), has unique characteristics relative to first-generation 5
      HT3RAs such as ondansetron. Nevertheless, it remains unclear if palonosetron is
      better than ondansetron for the prevention of nausea and vomiting during the
      first 24 hr after surgery and is thus the focus of this systematic review.
      METHODS: We conducted a systematic search of the MEDLINE(r), EMBASETM, Cochrane
      Central Register of Controlled Trials and Web of Science(r) databases to identify
      randomized controlled trials (RCTs) that addressed a comparison of the
      prophylactic antiemetic efficacy between palonosetron and ondansetron within 24
      hr after surgery. The primary outcomes were the proportion of participants who
      experienced postoperative nausea (PON), postoperative vomiting (POV), or both, in
      the early (0-6 hr) or late (6-24 hr) period. The pooled relative risks (RRs) were
      calculated along with their corresponding 95% confidence intervals (CIs).
      RESULTS: We identified nine RCTs that comprised 741 participants. Palonosetron
      was superior to ondansetron in the reduction of early PON [RR, 0.51; 95% CI, 0.37
      to 0.71], late PON (RR, 0.53; 95% CI, 0.36 to 0.77), and late POV (RR, 0.41; 95%
      CI, 0.28 to 0.62), but not early POV (RR, 0.77; 95% CI, 0.45 to 1.34).
      CONCLUSION: Palonosetron provides more effective prophylaxis of early PON, late
      PON, and late POV compared with ondansetron. Future studies are required to
      investigate the role of palonosetron during 24-72 hr following surgery.

PMID- 26296301
TI  - The "grey zone" or how to avoid the binary constraint of decision-making.

PMID- 26296302
TI  - Restricting the above ground sink corrects the root/shoot ratio and substantially
      boosts the yield potential per panicle in field-grown rice (Oryza sativa L.).
AB  - Rice has shallow, weak roots, but it is unknown how much increase in yield
      potential could be achieved if the root/shoot ratio is corrected. Removing all
      tillers except the main one, in a japonica (Sakha 101) and an indica (IR64) rice
      cultivar, instantly increased the root/shoot ratio from 0.21 to 1.16 in Sakha 101
      and from 0.16 to 1.46 in IR64. Over 30 days after detillering, the root/shoot
      ratios of the detillered plants decreased to 0.49 in Sakha 101 and 0.46 in IR64
      but remained significantly higher than in the controls. The detillered plants
      showed two- or fourfold increase in the main tiller fresh weight, as a
      consequence of more positive midday leaf relative water content (RWC), and
      consistently higher rates of stomatal conductance and photosynthesis, but not
      transpiration, compared with the controls. The enhanced photosynthesis in Sakha
      101 after detillering resulted from both improved water status and higher Rubisco
      contents whereas in IR64, increasing the Rubisco content did not contribute to
      improving photosynthesis. Detillering did not increase the carbohydrate contents
      of leaves but prevented starch depletion at the end of grain filling. The leaf
      protein content during vegetative and reproductive stages, the grain filling
      rate, the number of filled grains per panicle were greatly improved, bringing
      about 38.3 and 35.9% increase in the harvested grain dry weight per panicle in
      Sakha 101 and IR64, respectively. We provide evidence that improving the root
      performance by increasing the root/shoot ratio would eliminate the current
      limitations to photosynthesis and growth in rice. 

PMID- 26296303
TI  - Preparation of Polyamide-6 Submicrometer-Sized Spheres by In Situ Polymerization.
AB  - Polyamide-6 (PA6) submicron-sized spheres are prepared by two steps: (1) anionic
      ring-opening polymerization of epsilon-caprolactam in the presence of
      poly(ethylene glycol)-block-poly-(propylene glycol)-block-poly(ethylene
      glycol)(PEG-b-PPG-b-PEG) and (2) separation of PA6 spheres by dissolving PEG-b
      PPG-b-PEG from the prepared blends. The PA6 microspheres obtained are regular
      spherical, with diameter ranging from 200 nm to 2 MUm and narrow size
      distribution, as confirmed by scanning electron microscopy. By comparison with
      PA6/PS and PA6/PEG systems, it is denominated that the PEG blocks in PEG-b-PPG-b
      PEG can effectively reduce the surface tension of PA6 droplets and further
      decrease the diameter of the PA6 microspheres. The PPG block in PEG-b-PPG-b-PEG
      can prevent the PA6 droplets coalescing with each other, and isolated spherical
      particles can be obtained finally. The phase inversion of the PA6/PEG-b-PPG-b-PEG
      blends occurs at very low PEG-b-PPG-b-PEG content; the PEG-b-PPG-b-PEG phase can
      be removed by water easily. The whole experiment can be finished in a short time
      (approximately in half an hour) without using any organic solvents; it is an
      efficient strategy for the preparation of submicron-sized PA6 microspheres. 

PMID- 26296304
TI  - [Progression of coronary atherosclerosis].

PMID- 26296305
TI  - The postcentral sulcal complex and the transverse postcentral sulcus and their
      relation to sensorimotor functional organization.
AB  - It has been demonstrated that the postcentral sulcus, which forms the posterior
      boundary of the sensorimotor region, is a complex of distinct sulcal segments.
      Although the general somatotopic arrangement in the human sensorimotor cortex is
      relatively well known, we do not know whether the different segments of the
      postcentral sulcus relate in a systematic way to the sensorimotor functional
      representations. Participants were scanned with functional magnetic resonance
      imaging while they made movements of different body parts and the location of
      functional activity was examined on a subject-by-subject basis with respect to
      the morphological features of the postcentral sulcus. The findings demonstrate
      that the postcentral sulcus of each subject may be divided into five segments and
      there is a tight relationship between sensorimotor representations of different
      body parts and specific segments of the postcentral sulcus. The results also
      addressed the issue of the transverse postcentral sulcus, a short sulcus that is
      present within the ventral part of the postcentral gyrus in some brains. It was
      shown that, when present, this sulcus is functionally related to the oral (mouth
      and tongue) sensorimotor representation. When this sulcus is not present, the
      inferior postcentral sulcus which is also related to the oral representation is
      longer. Thus, the sulcal morphology provides an improved framework for functional
      assignments in individual subjects.

PMID- 26296306
TI  - A spatial assessment of baseline nutrient and water quality values in the Ashepoo
      Combahee-Edisto (ACE) Basin, South Carolina, USA.
AB  - The Ashepoo-Combahee-Edisto (ACE) Basin (South Carolina, USA) National Estuarine
      Research Reserve System (NERRS) encompasses some of the least developed USA
      coastline. Yet, periodic sampling showed that certain regions have higher
      nutrient, fecal coliform, and chlorophyll a levels, often with lower dissolved
      oxygen, than other South Carolina estuaries. To evaluate the spatial extent of
      these issues, a summer (2008) baseline study was conducted. Physical water
      quality, total nitrogen and phosphorus, chlorophyll a, dissolved organic carbon,
      and suspended solids were measured from surface waters of 67 stations (30 tidal
      creek, 37 open water). Nutrient and chlorophyll a levels were significantly
      (p<0.01) and negatively correlated with the extent of open water (% land cover),
      and chlorophyll a and nitrogen levels were, at times, elevated relative to
      concentrations typical of other estuaries in the state, reinforcing previous
      findings. This survey also identified several creeks not previously monitored
      that exhibited elevated nutrients.

PMID- 26296307
TI  - Modified iliofemoral approach with osteotomy of the iliac crest, sparing the
      abdominal muscles, for the treatment of acetabular fracture.
AB  - Treatment of acetabular fracture is complex, requiring adapted and often
      extensive surgical approaches. We describe a modified iliofemoral approach, with
      the particularity of including iliac crest osteotomy sparing abdominal muscles to
      allow direct control of reduction while respecting the abdominal muscles,
      creating a workspace as close to the fracture as possible, without involving the
      inguinal canal or femoral vascular-neural bundle. In 15 complex fractures, the
      technique provided 13 excellent or good reductions and 13 excellent or good
      results according to the Matta criteria. This approach can be combined with
      others, such as a posterior approach, thus providing an alternative to the
      ilioinguinal approach in the treatment of complex acetabular fracture. 

PMID- 26296308
TI  - No improvement in the post-TKA infection prognosis when the implant is not
      reimplanted: Retrospective multicentre study of 72 cases.
AB  - INTRODUCTION: For the surgeon and patient, permanent removal of an infected knee
      prosthesis is an unwelcome decision taken out of necessity because unfavourable
      local or general conditions may increase the likelihood of mechanical or
      infectious failure upon prosthesis reimplantation. The purpose of this study was
      to determine if permanent removal of an infected total knee arthroplasty (TKA)
      implant controls the infection and prevents above-the-knee amputation when
      reimplantation turns out to be too risky. It was hypothesized that removal
      without reimplantation contributes to eradicating the infection and helps to
      avoid amputation. PATIENTS AND METHODS: Seventy-two consecutive patients who
      underwent TKA removal between 2000 and 2010 at 14 hospitals were reviewed. The
      TKA removal was followed by knee fusion in 29 cases or implantation of a
      permanent cement spacer in 43 cases. RESULTS: If failure is defined as clinically
      obvious recurrence of the infection, the survival rate was 65 +/- 5% at 2 years;
      44% of patients had a recurrence of the infection, 8% had undergone amputation
      and 19% presented with nonunion at the last follow-up. The male gender and the
      presence of multiple co-morbidities were predisposing factors for failure.
      DISCUSSION: Control of the infection is not guaranteed upon TKA implant removal;
      the success rate is lower than in cases of two-stage reimplantation. The outcomes
      in this study are worse than those of other published studies. This is likely due
      to the heterogeneity in the patient population and treatments, along with the
      presence of co-morbidities. This treatment option should be the last recourse
      before amputation.

PMID- 26296309
TI  - Practice-based Research Network Research Good Practices (PRGPs): Summary of
      Recommendations.
AB  - INTRODUCTION: Practice-based research networks (PBRNs) conduct research in
      community settings, which poses quality control challenges to the integrity of
      research, such as study implementation and data collection. A foundation for
      improving research processes within PBRNs is needed to ensure research integrity.
      METHODS: Network directors and coordinators from seven U.S.-based PBRNs worked
      with a professional team facilitator during semiannual in-person meetings and
      monthly conference calls to produce content for a compendium of recommended
      research practices specific to the context of PBRNs. Participants were assigned
      to contribute content congruent with their expertise. Feedback on the draft
      document was obtained from attendees at the preconference workshop at the annual
      PBRN meeting in 2013. A revised document was circulated to additional PBRN peers
      prior to finalization. RESULTS: The PBRN Research Good Practices (PRGPs) document
      is organized into four chapters: (1) Building PBRN Infrastructure; (2) Study
      Development and Implementation; (3) Data Management, and (4) Dissemination
      Policies. Each chapter contains an introduction, detailed procedures for each
      section, and example resources with information links. CONCLUSION: The PRGPs is a
      PBRN-specific resource to facilitate PBRN management and staff training, to
      promote adherence to study protocols, and to increase validity and
      generalizability of study findings.

PMID- 26296310
TI  - The School Assessment for Environmental Typology (SAfETy): An Observational
      Measure of the School Environment.
AB  - School safety is of great concern for prevention researchers, school officials,
      parents, and students, yet there are a dearth of assessments that have
      operationalized school safety from an organizational framework using objective
      tools and measures. Such a tool would be important for deriving unbiased
      assessments of the school environment, which in turn could be used as an
      evaluative tool for school violence prevention efforts. The current paper
      presents a framework for conceptualizing school safety consistent with Crime
      Prevention through Environmental Design (CPTED) model and social disorganization
      theory, both of which highlight the importance of context as a driver for
      adolescents' risk for involvement in substance use and violence. This paper
      describes the development of a novel observational measure, called the School
      Assessment for Environmental Typology (SAfETy), which applies CPTED and social
      disorganizational frameworks to schools to measure eight indicators of school
      physical and social environment (i.e., disorder, trash, graffiti/vandalism,
      appearance, illumination, surveillance, ownership, and positive behavioral
      expectations). Drawing upon data from 58 high schools, we provide preliminary
      data regarding the validity and reliability of the SAfETy and describe patterns
      of the school safety indicators. Findings demonstrate the reliability and
      validity of the SAfETy and are discussed with regard to the prevention of
      violence in schools.

PMID- 26296311
TI  - Paving the way for adequate myelination: The contribution of galectin-3,
      transferrin and iron.
AB  - Considering the worldwide incidence of well characterized demyelinating disorders
      such as Multiple Sclerosis (MS) and the increasing number of pathologies recently
      found to involve hypomyelinating factors such as micronutrient deficits,
      elucidating the molecular basis of central nervous system (CNS) demyelination,
      remyelination and hypomyelination becomes essential to the development of future
      neuroregenerative therapies. In this context, this review discusses novel
      findings on the contribution of galectin-3 (Gal-3), transferrin (Tf) and iron to
      the processes of myelination and remyelination and their potentially positive
      regulation of oligodendroglial precursor cell (OPC) differentiation. Studies were
      conducted in cuprizone (CPZ)-induced demyelination and iron deficiency (ID)
      induced hypomyelination, and the participation of glial and neural stem cells
      (NSC) in the remyelination process was evaluated by means of both in vivo and in
      vitro assays on primary cell cultures. 

PMID- 26296312
TI  - MicroRNA-454 functions as an oncogene by regulating PTEN in uveal melanoma.
AB  - MicroRNAs (miRNAs) regulate gene expression by targeted repression of
      transcription and translation, and are involved in carcinogenesis. In this study,
      we demonstrated that the expression of miR-454 was up-regulated in uveal melanoma
      tissues compared to normal tissues. Ectopic expression of miR-454 resulted in
      significant promotion of cell proliferation, colony formation, invasion and
      induction of cell cycle in uveal melanoma cells. Furthermore, we identified PTEN
      as a direct target of miR-454. Our data revealed that ectopic expression of PTEN
      restored the effects of miR-454 on cell proliferation and invasion in uveal
      melanoma cells. These findings support an oncogene role of miR-454 in development
      of uveal melanoma. 

PMID- 26296313
TI  - Lipopolysaccharide induction of REDD1 is mediated by two distinct CREB-dependent
      mechanisms in macrophages.
AB  - REDD1 is induced by various cellular stresses; however, its expression in
      response to lipopolysaccharide (LPS) has not been clearly elucidated in immune
      cells. LPS stimulated CREB-dependent and NF-kappaB-independent REDD1 expression
      in macrophages. Early increases in CREB phosphorylation and REDD1 expression at
      8h following LPS treatment were blocked by inhibition of p38MAPK and mitogen- and
      stress-activated protein kinase 1 (MSK1), but not PKA. However, delayed CREB
      mediated REDD1 expression at 16h was suppressed by inhibition of cyclooxygenase-2
      (COX-2) and PKA. It indicates that LPS induces REDD1 expression by two distinct
      CREB-mediated mechanisms, the early p38MAPK/MSK1 and the delayed COX-2/PGE2/PKA
      pathways. 

PMID- 26296314
TI  - NAD(+)-aminoaldehyde dehydrogenase candidates for 4-aminobutyrate (GABA) and beta
      alanine production during terminal oxidation of polyamines in apple fruit.
AB  - The last step of polyamine catabolism involves the oxidation of 3-aminopropanal
      or 4-aminobutanal via aminoaldehyde dehydrogenase. In this study, two apple
      (Malus x domestica) AMADH genes were selected (MdAMADH1 and MdAMADH2) as
      candidates for encoding 4-aminobutanal dehydrogenase activity. Maximal activity
      and catalytic efficiency were obtained with NAD(+) and 3-aminopropanal, followed
      by 4-aminobutanal, at pH 9.8. NAD(+) reduction was accompanied by the production
      of GABA and beta-alanine, respectively, when 4-aminobutanal and 3-aminopropanal
      were utilized as substrates. MdAMADH2 was peroxisomal and MdAMADH1 cytosolic.
      These findings shed light on the potential role of apple AMADHs in 4
      aminobutyrate and beta-alanine production. 

PMID- 26296315
TI  - Mice doubly-deficient in the Arf GAPs SMAP1 and SMAP2 exhibit embryonic
      lethality.
AB  - In mammals, the small Arf GTPase-activating protein (SMAP) subfamily of Arf
      GTPase-activating proteins consists of closely related members, SMAP1 and SMAP2.
      These factors reportedly exert distinct functions in membrane trafficking, as
      manifested by different phenotypes seen in single knockout mice. The present
      study investigated whether SMAP proteins interact genetically. We report for the
      first time that simultaneous loss of SMAP1 and SMAP2 promotes apoptosis in the
      distal region of E7.5 mouse embryos, likely resulting in embryonic lethality.
      Thus, at least one SMAP gene, either SMAP1 or SMAP2, is required for proper
      embryogenesis. 

PMID- 26296316
TI  - Inhibition of Yap2 activity by MAPKAP kinase Rck1 affects yeast tolerance to
      cadmium.
AB  - Yap2 is a cadmium responsive transcription factor that interacts with MAPK
      activated protein (MAPKAP) kinase Rck1. We show that Rck1 deletion confers
      protection against cadmium toxicity and that the mechanism underlying this
      observation relies on Yap2. Rck1 removal from the yeast genome potentiates Yap2
      activity by increasing protein half-life and delaying its nuclear export. As a
      consequence, several Yap2 antioxidant targets are over-activated by a mechanism
      that also requires Yap1. Several genes of the cell wall integrity (CWI) pathway
      are upregulated under cadmium stress in a Yap2 dependent way. We showed that
      deletion of CWI genes renders yeast cells more sensitive to cadmium. These
      findings led us to suggest that in response to cadmium stress Yap2 may serve a
      dual purpose: oxidative stress attenuation and cell wall maintenance. 

PMID- 26296317
TI  - Identification and evolution of the orphan genes in the domestic silkworm, Bombyx
      mori.
AB  - Orphan genes (OGs) which have no recognizable homology to any sequences in other
      species could contribute to the species specific adaptations. In this study, we
      identified 738 OGs in the silkworm genome. About 31% of the silkworm OGs is
      derived from transposable elements, and 5.1% of the silkworm OGs emerged from
      gene duplication followed by divergence of paralogs. Five de novo silkworm OGs
      originated from non-coding regions. Microarray data suggested that most of the
      silkworm OGs were expressed in limited tissues. RNA interference experiments
      suggested that five de novo OGs are not essential to the silkworm, implying that
      they may contribute to genetic redundancy or species-specific adaptation. Our
      results provide some new insights into the evolutionary significance of the
      silkworm OGs. 

PMID- 26296318
TI  - Fatty acid transport and transporters in muscle are critically regulated by Akt2.
AB  - Muscle contains various fatty acid transporters (CD36, FABPpm, FATP1, FATP4).
      Physiological stimuli (insulin, contraction) induce the translocation of all four
      transporters to the sarcolemma to enhance fatty acid uptake similarly to glucose
      uptake stimulation via glucose transporter-4 (GLUT4) translocation. Akt2 mediates
      insulin-induced, but not contraction-induced, GLUT4 translocation, but its role
      in muscle fatty acid transporter translocation is unknown. In muscle from Akt2
      knockout mice, we observed that Akt2 is critically involved in both insulin
      induced and contraction-induced fatty acid transport and translocation of fatty
      acid translocase/CD36 (CD36) and FATP1, but not of translocation of fatty acid
      binding protein (FABPpm) and FATP4. Instead, Akt2 mediates intracellular
      retention of both latter transporters. Collectively, our observations reveal
      novel complexities in signaling mechanisms regulating the translocation of fatty
      acid transporters in muscle. 

PMID- 26296319
TI  - Chromatin, DNA structure and alternative splicing.
AB  - Coupling of transcription and alternative splicing via regulation of the
      transcriptional elongation rate is a well-studied phenomenon. Template features
      that act as roadblocks for the progression of RNA polymerase II comprise histone
      modifications and variants, DNA-interacting proteins and chromatin compaction.
      These may affect alternative splicing decisions by inducing pauses or decreasing
      elongation rate that change the time-window for splicing regulatory sequences to
      be recognized. Herein we discuss the evidence supporting the influence of
      template structural modifications on transcription and splicing, and provide
      insights about possible roles of non-B DNA conformations on the regulation of
      alternative splicing. 

PMID- 26296320
TI  - Voltage-gated proton (H(v)1) channels, a singular voltage sensing domain.
AB  - The main role of voltage-gated proton channels (Hv1) is to extrude protons from
      the intracellular milieu when, mediated by different cellular processes, the H(+)
      concentration increases. Hv1 are exquisitely selective for protons and their
      structure is homologous to the voltage sensing domain (VSD) of other voltage
      gated ion channels like sodium, potassium, and calcium channels. In clear
      contrast to the classical voltage-dependent channels, Hv1 lacks a pore domain and
      thus permeation necessarily occurs through the voltage sensing domain. Hv1
      channels are activated by depolarizing voltages, and increases in internal proton
      concentration. It has been proposed that local conformational changes of the
      transmembrane segment S4, driven by depolarization, trigger the molecular
      rearrangements that open Hv1. However, it is still unclear how the
      electromechanical coupling is achieved between the VSD and the potential pore,
      allowing the proton flux from the intracellular to the extracellular side. Here
      we provide a revised view of voltage activation in Hv1 channels, offering a
      comparative scenario with other voltage sensing channels domains. 

PMID- 26296321
TI  - eMouseAtlas informatics: embryo atlas and gene expression database.
AB  - A significant proportion of developmental biology data is presented in the form
      of images at morphologically diverse stages of development. The curation of these
      datasets presents different challenges to that of sequence/text-based data.
      Towards this end, the eMouseAtlas project created a digital atlas of mouse embryo
      development as a means of understanding developmental anatomy and exploring the
      relationship between genes and development in a spatial context. Using the
      morphological staging system pioneered by Karl Theiler, the project has generated
      3D models of post-implantation mouse development and used them as a spatial
      framework for the delineation of anatomical components and for archiving in situ
      gene expression data in the EMAGE database. This has allowed us to develop a
      unique online resource for mouse developmental biology. We describe here the
      underlying structure of the resource, as well as some of the tools that have been
      developed to allow users to mine the curated image data. These tools include our
      IIP3D/X3DOM viewer that allows 3D visualisation of anatomy and/or gene expression
      in the context of a web browser, and the eHistology resource that extends this
      functionality to allow visualisation of high-resolution cellular level images of
      histology sections. Furthermore, we review some of the informatics aspects of
      eMouseAtlas to provide a deeper insight into the use of the atlas and gene
      expression database. 

PMID- 26296322
TI  - New animal models reveal that coenzyme Q2 (Coq2) and placenta-specific 8 (Plac8)
      are candidate genes for the onset of type 2 diabetes associated with obesity in
      rats.
AB  - Obesity is a major risk factor for the onset of type 2 diabetes; however, little
      is known about the gene(s) involved. Therefore, we developed new animal models of
      obesity to search for diabetogenic genes associated with obesity. We generated
      double congenic rat strains with a hyperglycaemic quantitative trait locus (QTL)
      derived from the Otsuka Long-Evans Tokushima Fatty rat and a fa/fa (Lepr-/-)
      locus derived from the Zucker Fatty rat; phenotypic analysis for plasma glucose
      and insulin levels and RNA and protein levels were determined using reverse
      transcription quantitative PCR and Western blotting analyses, respectively. The
      double congenic strain F344-fa-nidd2 (Lepr-/- and Nidd2/of) exhibited
      significantly higher glucose levels and significantly lower hypoglycaemic
      response to insulin than the obese control strain F344-fa (Lepr-/-). These
      phenotypes were clearly observed in the obese strains but not in the lean
      strains. These results indicate that the Nidd2/of locus harbours a diabetogenic
      gene associated with obesity. We measured the expression of 60 genes in the
      Nidd2/of QTL region between the strains and found that the mRNA expression levels
      of five genes were significantly different between the strains under the
      condition of obesity. However, three of the five genes were differentially
      expressed in both obese and lean rats, indicating that these genes are not
      specific for the condition of obesity. Conversely, the other two genes, coenzyme
      Q2 (Coq2) and placenta-specific 8 (Plac8), were differentially expressed only in
      the obese rats, suggesting that these two genes are candidates for the onset of
      type 2 diabetes associated with obesity in rats.

PMID- 26296323
TI  - Neurotensin enhances glutamatergic EPSCs in VTA neurons by acting on different
      neurotensin receptors.
AB  - Neurotensin (NT) is an endogenous neuropeptide that modulates dopamine and
      glutamate neurotransmission in several limbic regions innervated by neurons
      located in the ventral tegmental area (VTA). While several studies showed that NT
      exerted a direct modulation on VTA dopamine neurons less is known about its role
      in the modulation of glutamatergic neurotransmission in this region. The present
      study was aimed at characterising the effects of NT on glutamate-mediated
      responses in different populations of VTA neurons. Using whole cell patch clamp
      recording technique in horizontal rat brain slices, we measured the amplitude of
      glutamatergic excitatory post-synaptic currents (EPSCs) evoked by electrical
      stimulation of VTA afferents before and after application of different
      concentrations of NT1-13 or its C-terminal fragment, NT8-13. Neurons were
      classified as either Ih(+) or Ih(-) based on the presence or absence of a
      hyperpolarisation activated cationic current (Ih). We found that NT1-13 and NT8
      13 produced comparable concentration dependent increase in the amplitude of EPSCs
      in both Ih(+) and Ih(-) neurons. In Ih(+) neurons, the enhancement effect of NT8
      13 was blocked by both antagonists, while in Ih(-) neurons it was blocked by the
      NTS1/NTS2 antagonist, SR142948A, but not the preferred NTS1 antagonist, SR48692.
      In as much as Ih(-) neurons are non-dopaminergic neurons and Ih(+) neurons
      represent both dopamine and non-dopamine neurons, we can conclude that NT
      enhances glutamatergic mediated responses in dopamine, and in a subset of non
      dopamine, neurons by acting respectively on NTS1 and an NT receptor other than
      NTS1. 

PMID- 26296324
TI  - Altered hepatic mRNA expression of immune response-associated DNA damage in mice
      liver induced by potassium bromate: Protective role of vanillin.
AB  - Chronic exposure to potassium bromate (KBrO3 ), a toxic halogen existing widely
      in the environment, environment through contaminated drinking water, has become a
      global problem of public health. The present study investigates the protective
      role of vanillin against KBrO3 induced oxidative stress, distruption in
      inflammatory cytokines expression, DNA damage, and histopathological changes.
      Adult mice were exposed orally to KBrO3 (2g/L of drinking water) for 2 weeks The
      co-administration of vanillin to the KBrO3 -treated mice significantly prevented
      the plasma transaminases increase in. Furthermore, it inhibited hepatic lipid
      peroxidation (malondialdehyde), advanced oxidation protein product (AOPP) and
      protein carbonyl (PCO) formation and attenuated the KBrO3 -mediated depletion of
      enzymatic and non enzymatic antioxidants catalase, superoxide dismutase, and
      glutathione peroxidase activities and glutathione level in the liver. In
      addition, vanillin markedly attenuated the expression levels of proinflammatory
      cytokines, including tumor necrosis factor-alpha, interleukin-1beta, interleukin
      6, and COX2 and prevented KBrO3 -induced hepatic cell alteration and necrosis, as
      indicated by histopathological data. DNA damage, as assessed by the alkaline
      comet assay, was also found to be low in the co-treated group. Thus, these
      findings show that vanillin acts as potent chemopreventive agent against KBrO3 
      mediated liver oxidative stress and genotoxicity through its antioxidant
      properties. (c) 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1796-1807, 2016.

PMID- 26296325
TI  - Phylogenetic analysis of the emergence of main hepatitis C virus subtypes in Sao
      Paulo, Brazil.
AB  - BACKGROUND: It is recognized that hepatitis C virus subtypes (1a, 1b, 2a, 2b, 2c
      and 3a) originated in Africa and Asia and spread worldwide exponentially during
      the Second World War (1940) through the transfusion of contaminated blood
      products, invasive medical and dental procedures, and intravenous drug use. The
      entry of hepatitis C virus subtypes into different regions occurred at distinct
      times, presenting exponential growth rates of larger or smaller spread. Our study
      estimated the growth and spread of the most prevalent subtypes currently
      circulating in Sao Paulo. METHODS: A total of 465 non-structural region 5B
      sequences of hepatitis C virus covering a 14-year time-span were used to
      reconstruct the population history and estimate the population dynamics and Time
      to Most Recent Common Ancestor of genotypes using the Bayesian Markov Chain Monte
      Carlo approach implemented in BEAST (Bayesian evolutionary analysis by sampling
      tree software/program). RESULTS: Evolutionary analysis demonstrated that the
      different hepatitis C virus subtypes had distinct growth patterns. The
      introduction of hepatitis C virus-1a and -3a were estimated to be circa 1979 and
      1967, respectively, whereas hepatitis C virus-1b appears to have a more ancient
      entry, circa 1923. Hepatitis C virus-1b phylogenies suggest that different
      lineages circulate in Sao Paulo, and four well-supported groups (i.e., G1, G2, G3
      and G4) were identified. Hepatitis C virus-1a presented the highest growth rate
      (r=0.4), but its spread became less marked after the 2000s. Hepatitis C virus-3a
      grew exponentially until the 1990s and had an intermediate growth rate (r=0.32).
      An evident exponential growth (r=0.26) was found for hepatitis C virus-1b between
      1980 and the mid-1990s. CONCLUSIONS: After an initial period of exponential
      growth, the expansion of the three main subtypes began to decrease. Hepatitis C
      virus-1b presented inflated genetic diversity, and its transmission may have been
      sustained by different generations and transmission routes other than blood
      transfusion. Hepatitis C virus-1a and -3a showed no group stratification, most
      likely due to their recent entry.

PMID- 26296326
TI  - Prediction of brain atrophy using three drug scores in neuroasymptomatic HIV
      infected patients with controlled viremia.
AB  - BACKGROUND: Despite potent antiretroviral therapy, HIV still causes brain damage.
      Better penetration into the CNS and efficient elimination of monocyte/macrophages
      reservoirs are two main characteristics of an antiretroviral drug that could
      prevent brain damage. The aim of our study was to assess efficacy of three
      antiretroviral drug scores to predict brain atrophy in HIV-infected patients.
      METHODS: A cross sectional study consisting of 56 HIV-infected patients with
      controlled viremia, who had no clinically evident neurocognitive impairment. All
      patients had MRI of the head. A typical T2 transversal slice was analyzed and
      ventricles-brain ratio (VBr) as an overall brain atrophy index was calculated.
      Three antiretroviral drug scores were used and correlated with VBr: 2008 and 2010
      CNS penetration effectiveness scores (SigmaCPE2008 and SigmaCPE2010) and the
      recently established monocyte efficacy (SigmaME) score. A p-value <0.05 was
      considered significant. RESULTS: SigmaCPE2010 was significantly associated with
      VBr in both univariate (r=-0.285, p=0.033) and multivariate (beta=-0.299,
      p=0.016) regression models, while SigmaCPE2008 was not (r=-0.141, p=0.300 and
      beta=-0.156, p=0.214). SigmaME was associated with VBr in multivariate model only
      (r=-0.297, p=0.111 and beta=-0.406, p=0.029). Age and reported duration of HIV
      infection were also significant predictors of overall brain atrophy in
      multivariate regression models. CONCLUSIONS: Although based on similar type of
      research, SigmaCPE2010 is a superior drug score compared to SigmaCPE2008. SigmaME
      is an efficient drug score in determining brain damage. Both SigmaCPE2010 and
      SigmaME scores should be taken into account in preventive strategies of brain
      atrophy and neurocognitive impairment in HIV-infected patients.

PMID- 26296327
TI  - Premature ventricular contraction-induced cardiomyopathy: Related clinical and
      electrophysiologic parameters.
AB  - BACKGROUND: Factors associated with premature ventricular contraction-induced
      cardiomyopathy (PVCi-CMP) remain debated. OBJECTIVE: The purpose of this study
      was to test the correlation of various factors to the presence PVCi-CMP in a
      large multicenter population. METHODS: One hundred sixty-eight consecutive
      patients referred for ablation of frequent premature ventricular contractions
      (PVCs) were included. Patients were divided into 2 groups: group 1 with suspected
      PVCi-CMP (96 patients, ejection fraction 38% +/- 10%, left ventricular end
      diastolic diameter 62 +/- 8 mm, with or without additional structural heart
      disease); and group 2 (control group, 72 patients with normal ejection fraction
      and left ventricular dimensions). Various clinical and electrophysiologic
      parameters were compared between groups. RESULTS: In univariate analysis, left
      ventricular origin of PVC, lack of palpitations, long PVC coupling interval,
      epicardial origin of the focus, long sinus beat QRS duration, male gender, high
      PVC burden, presence of polymorphic PVCs, high PVC QRS duration, and older age
      were significantly related to the presence of PVCi-CMP. In multivariate analysis,
      only lack of palpitations, PVC burden, and epicardial origin remained
      significantly and independently correlated with the presence of cardiomyopathy.
      Even if sinus QRS duration or PVC left ventricular origin were also found
      independently linked to PVCi-CMP in the whole population, they were no longer
      correlated when patients with additional heart disease were excluded. CONCLUSION:
      Lack of palpitations, PVC burden, and epicardial origin are independent factors
      that identify patients prone to developing PVCi-CMP.

PMID- 26296328
TI  - Alignment of cryo-EM movies of individual particles by optimization of image
      translations.
AB  - Direct detector device (DDD) cameras have revolutionized single particle electron
      cryomicroscopy (cryo-EM). In addition to an improved camera detective quantum
      efficiency, acquisition of DDD movies allows for correction of movement of the
      specimen, due to both instabilities in the microscope specimen stage and electron
      beam-induced movement. Unlike specimen stage drift, beam-induced movement is not
      always homogeneous within an image. Local correlation in the trajectories of
      nearby particles suggests that beam-induced motion is due to deformation of the
      ice layer. Algorithms have already been described that can correct movement for
      large regions of frames and for >1 MDa protein particles. Another algorithm
      allows individual <1 MDa protein particle trajectories to be estimated, but
      requires rolling averages to be calculated from frames and fits linear
      trajectories for particles. Here we describe an algorithm that allows for
      individual <1 MDa particle images to be aligned without frame averaging or linear
      trajectories. The algorithm maximizes the overall correlation of the shifted
      frames with the sum of the shifted frames. The optimum in this single objective
      function is found efficiently by making use of analytically calculated
      derivatives of the function. To smooth estimates of particle trajectories, rapid
      changes in particle positions between frames are penalized in the objective
      function and weighted averaging of nearby trajectories ensures local correlation
      in trajectories. This individual particle motion correction, in combination with
      weighting of Fourier components to account for increasing radiation damage in
      later frames, can be used to improve 3-D maps from single particle cryo-EM.

PMID- 26296329
TI  - Structural and computational dissection of the catalytic mechanism of the
      inorganic pyrophosphatase from Mycobacterium tuberculosis.
AB  - Family I inorganic pyrophosphatases (PPiases) are ubiquitous enzymes that are
      critical for phosphate metabolism in all domains of life. The detailed catalytic
      mechanism of these enzymes, including the identity of the general base, is not
      fully understood. We determined a series of crystal structures of the PPiase from
      Mycobacterium tuberculosis (Mtb PPiase) bound to catalytic metals, inorganic
      pyrophosphate (PPi; the reaction substrate) and to one or two inorganic phosphate
      ions (Pi; the reaction product), ranging in resolution from 1.85 to 3.30A. These
      structures represent a set of major kinetic intermediates in the catalytic
      turnover pathway for this enzyme and suggest an order of association and
      dissociation of the divalent metals, the substrate and the two products during
      the catalytic turnover. The active site of Mtb PPiase exhibits significant
      structural differences from the well characterized Escherichia coli PPiase in the
      vicinity of the bound PPi substrate. Prompted by these differences, quantum
      mechanics/molecular mechanics (QM/MM) analysis yielded an atomic description of
      the hydrolysis step for Mtb PPiase and, unexpectedly, indicated that Asp89,
      rather than Asp54 that was proposed for E. coli PPiase, can abstract a proton
      from a water molecule to activate it for a nucleophilic attack on the PPi
      substrate. Mutagenesis studies of the key Asp residues of Mtb PPiase supported
      this mechanism. This combination of structural and computational analyses
      clarifies our understanding of the mechanism of family I PPiases and has
      potential utility for rational development of drugs targeting this enzyme. 

PMID- 26296330
TI  - A Study of the Possible Harmful Effects of Cosmetic Beauty Products on Human
      Health.
AB  - The origins of the usage of different substances in beauty, skin, body, hair, and
      nails care products can be found in ancient times. To achieve better quality and
      enhance their effects, some additives such as preservatives, stabilizers, mineral
      pigments, dye, and shine were added to these products. Some of these substances
      may also have allergic, irritating, and harmful effects on human health. The aim
      of this study was the optimization of the potentiometric stripping analysis (PSA)
      for the purpose of determining the content of heavy metals (lead, cadmium, zinc),
      in some commercial cosmetic beauty products (lipsticks, lip glosses, eye shadows,
      and henna hair dye). In addition, in order to monitor the potential adverse
      effects of henna dye on hair quality, as well as the total body burden of heavy
      metals (Pb, Cd), the paper analyzed hair samples before and after henna dye
      treatment. Beauty products used for cosmetic purposes can have adverse effects to
      human health due to the fact that they contain lead, a highly toxic metal. The
      lead content in the tested samples varied depending on the additives used along
      with the method of production. The cosmetic products that were analyzed in this
      study contained a certain amount of zinc, which is an essential element, although
      its content above the prescribed limit may lead to side effects. Highly toxic
      metal, cadmium, was not detected in the tested samples. The presence of these
      metals in cosmetic products certainly indicate that it is necessary to monitor
      and determinate the content of toxic heavy metals in these products, especially
      because they are in direct contact with skin or mucous membranes and are often
      used in daily life. 

PMID- 26296331
TI  - Role of PTEN-Akt-CREB Signaling Pathway in Nervous System impairment of Rats with
      Chronic Arsenite Exposure.
AB  - The nervous system is a target of arsenic toxicity. Phosphatase and tensin
      homologue deleted on chromosome 10/protein kinase B/cAMP-response element binding
      protein (PTEN/Akt/CREB) signaling pathway has been reported to be involved in
      maintaining normal function of the nervous system, modulating growth and
      proliferation of neurocyte, regulating neuron synaptic plasticity, and long-term
      memory. And many studies have demonstrated that expressions of PTEN, Akt, and
      CREB protein were influenced by arsenic, but it is not clear whether this
      signaling pathway is involved in the nervous system impairment of rats induced by
      chronic arsenite exposure, and we have addressed this in this study. Eighty male
      Sprague-Dawley (SD) rats were randomly divided into eight groups (n = 10 each),
      four groups exposed to NaAsO2 (0, 5, 10, and 50 mg/L NaAsO2 in drinking water)
      for 3 months, the other four groups exposed to NaAsO2 (0, 5, 10, 50 mg/L NaAsO2
      in drinking water) for 6 months. Hematoxylin and eosin (HE) staining showed that
      chronic arsenite exposure induced varying degrees of damage in cerebral neurons.
      And arsenite exposure increased arsenic amount in serum and brain samples in a
      dose- and time-dependent manner. Moreover, the protein levels of PTEN and Akt in
      brain tissue were not significantly changed compared with the control group, but
      p-Akt, CREB, and p-CREB were all significantly downregulated in arsenite-exposed
      groups with a dose-dependent pattern. These results suggested that chronic
      arsenite exposure negatively regulated the PTEN-Akt-CREB signaling pathway, and
      dysfunction of the signaling pathway might be one of the mechanisms of nervous
      system impairment induced by chronic arsenite exposure.

PMID- 26296332
TI  - Interference competition: odours of an apex predator and conspecifics influence
      resource acquisition by red foxes.
AB  - Apex predators can impact smaller predators via lethal effects that occur through
      direct killing, and non-lethal effects that arise when fear-induced behavioural
      and physiological changes reduce the fitness of smaller predators. A general
      outcome of asymmetrical competition between co-existing predator species is that
      larger predators tend to suppress the abundances of smaller predators. Here, we
      investigate interference effects that an apex predator, the dingo (Canis dingo),
      has on the acquisition of food and water by the smaller red fox (Vulpes vulpes),
      by exposing free-ranging foxes to the odour of dingoes and conspecifics in an
      arid environment. Using giving-up densities we show that foxes foraged more
      apprehensively at predator-odour treatments than unscented controls, but their
      food intake did not differ between dingo- and fox-odour treatments. Using video
      analysis of fox behaviour at experimental water stations we show that foxes spent
      more time engaged in exploration behaviour at stations scented with fox odour and
      spent more time drinking at water stations scented with dingo odour. Our results
      provide support for the idea that dingo odour exerts a stronger interference
      effect on foxes than conspecific odour, but suggest that the odours of both
      larger dingoes and unfamiliar conspecifics curtailed foxes' acquisition of food
      resources. 

PMID- 26296334
TI  - Solvolysis of 14,17-etheno-bridged 16alpha-nitroestratrienyl acetate and lactam
      formation pathways studied by LC-NMR and LC-MS. Structures of minor products.
AB  - The ethanol solvolysis of 3-methoxy-14,17-etheno-16alpha-nitroestra-1,3,5(10)
      trien-17beta-yl acetate in the presence of NaHCO3 was studied by means of real
      time NMR experiments, LC-SPE-NMR, and LC-MS. The pathway to form 3-methoxy-2'
      oxopyrrolidino-[4',5':14beta,15beta]-estra-1,3,5(10)-trien-17-one was disclosed.
      The intermediacy of nitrile oxide and alkoxynitrone was postulated based on the
      analysis of the reaction products. The proposed mechanism of cleaving the bridge
      in the nitro compound is legal for the formation of N-acetoxylactams, nitriles,
      isoxazoles and isoxazolines. 

PMID- 26296333
TI  - Costs and benefits of plant allelochemicals in herbivore diet in a multi enemy
      world.
AB  - Sequestration of plant defensive chemicals by herbivorous insects is a way of
      defending themselves against their natural enemies. Such herbivores have
      repeatedly evolved bright colours to advertise their unpalatability to predators,
      i.e. they are aposematic. This often comes with a cost. In this study, we
      examined the costs and benefits of sequestration of iridoid glycosides (IGs) by
      the generalist aposematic herbivore, the wood tiger moth, Parasemia plantaginis.
      We also asked whether the defence against one enemy (a predator) is also
      effective against another (a parasitoid). We found that the larvae excrete most
      of the IGs and only small amounts are found in the larvae. Nevertheless, the
      amounts present in the larvae are sufficient to deter ant predators and also play
      a role in defence against parasitoids. However, excreting and handling these
      defensive plant compounds is costly, leading to longer development time and lower
      pupal mass. Interestingly, the warning signal efficiency and the amount of IGs in
      the larvae of P. plantaginis are negatively correlated; larvae with less
      efficient warning signals contain higher levels of chemical defence compounds.
      Our results may imply that there is a trade-off between production and
      maintenance of coloration and chemical defence. Although feeding on a diet
      containing IGs can have life-history costs, it offers multiple benefits in the
      defence against predators and parasitoids. 

PMID- 26296335
TI  - Frequency of transmitted drug resistance mutations among treatment-naive HIV-1
      infected individuals at a tertiary care centre in South India.
AB  - INTRODUCTION: Morbidity and mortality among HIV-1-infected individuals has been
      dramatically reduced by the implementation of combinational antiretroviral
      therapy (ART). However, the efficiency of these therapies is compromised due to
      HIV-1 transmitted drug resistance mutations (TDRMs). METHODS: We collected a
      total of 127 samples from ART-naive HIV-infected individuals and sequenced the
      pol gene and analysed for drug resistance mutations using the Calibrated
      Population Resistance (CPR) tool in the Stanford database. RESULTS: All the 127
      clinical samples (100 %) were identified as HIV-1 subtype C. Based on the CPR
      tool, three strains (2.4 %) had TDRMs, and these were K101E, Y181C and G190A. Our
      findings correlated well with the WHO surveys conducted in Asia, including India,
      which consistently reported <5 % TDRM among the specific populations assessed.
      CONCLUSION: In countries like India, regular monitoring of TDRMs will provide
      better information for clinical practice improvement and policy making.

PMID- 26296336
TI  - Prevalence and correlates of apathy in myotonic dystrophy type 1.
AB  - BACKGROUND: Apathy in DM1 has long been acknowledged in clinical practice.
      However, a major drawback is that the concept has been only sparsely explored in
      previous specific studies. This study aimed to determine the prevalence of apathy
      in myotonic dystrophy (DM1), to compare it with facioscapulohumeral dystrophy
      (FSHD) patients and normal healthy controls, and explore its relationship to
      psychopathological features and cognitive function. METHODS: Levels of apathy in
      38 DM1 patients with adult phenotypes were compared with 19 patients with FSHD
      and 20 matched controls. Patient participants were consecutively recruited,
      regarding their interdisciplinary annual evaluation at the neuromuscular
      pathology reference center (Institute of Myology, Paris, France), within an 18
      month period. Additional measurements included motor disability, fatigue,
      depression, anxiety, and cognitive abilities. Inter-group comparisons were
      performed using non-parametric Kruskal-Wallis tests and Mann-Whitney U Tests.
      Intra-group comparisons were carried out with the Wilcoxon Signed rank and
      Friedman tests. Also, Spearman's correlations were used to assess the strength of
      linear relationships between pairs of variables. The significance level was set
      at 0.05. RESULTS: Global score of apathy was significantly higher in DM1 patients
      than in FSHD patients (p < 0.01) and in controls (p < 0.001). Sixteen of 38 DM1
      patients (39.5 %) met the criterion for apathy, contrasting with only 4 of the 19
      (21.1 %) FSHD patients. No control subject was apathetic. Moreover, apathy in DM1
      patients was negatively correlated to MMSE (r = -.46, p < .05) and Stroop Word (r
      = -.55, p < .01) scores, but not with age, educational level, disease duration,
      CTG repeats, motor functional disability, fatigue, depression, and anxiety.
      CONCLUSIONS: Apathy is a frequent symptom in DM1 (almost 40 %). It is more
      prevalent than in a similarly disabled group of patients with FSHD and in
      controls. Results also show that apathy in DM1 is independent of the
      psychopathological domain, fatigue, age, and motor disability, but associated to
      general cognitive status. These results altogether could suggest a central cause
      for apathy in DM1 rather than an adjustment process to cope with the progressive
      and debilitating nature of the disease. Data emphasize the importance to evaluate
      this symptom in routine clinical management of DM1 patients.

PMID- 26296337
TI  - Microbacterium rhizomatis sp. nov., a beta-glucosidase-producing bacterium
      isolated from rhizome of Korean mountain ginseng.
AB  - A novel Gram-staining-positive, rod-shaped bacterium, designated DCY100(T), was
      isolated from rhizome of mountain ginseng root in Hwacheon mountain, Gangwon
      province, Republic of Korea. The 16S rRNA gene sequence analysis showed that
      strain DCY100(T) belonged to the genus Microbacterium and was most closely
      related to Microbacterium ginsengisoli KCTC 19189(T) (97.9%), Microbacterium
      lacus JCM 15575(T) (97.2%) and Microbacterium invictum DSM 19600(T) (97.1%). The
      major menaquinones were MK-11 and MK-12. The major polar lipids were found to be
      diphosphatidylglycerol, phosphatidylglycerol and one unidentified glycolipid. The
      major fatty acids (>10.0%) were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0.
      The cell-wall peptidoglycan contained the amino acids ornithine, alanine,
      glutamic acid and glycine; whole-cell sugars consisted of glucose, galactose,
      rhamnose and ribose. The DNA G+C content was 63.6 +/- 0.7 mol%. The DNA-DNA
      hybridization relatedness values between strain DCY100(T) and Microbacterium
      ginsengisoli KCTC 19189(T), Microbacterium lacus JCM 15575(T) and Microbacterium
      invictum DSM 19600(T) were 36.2 +/- 0.4, 22.0 +/- 3.0 and 15.3 +/- 1.8%,
      respectively. On the basis of phenotypic, chemotaxonomic and genotypic analyses,
      the isolate is classified as a representative of a novel species in the genus
      Microbacterium, for which the name Microbacterium rhizomatis DCY100(T) is
      proposed. The type strain is DCY100(T) ( = KCTC 39529(T) = JCM 30598(T)).

PMID- 26296338
TI  - Transcriptomic changes in the plant pathogenic fungus Rhizoctonia solani AG-3 in
      response to the antagonistic bacteria Serratia proteamaculans and Serratia
      plymuthica.
AB  - BACKGROUND: Improved understanding of bacterial-fungal interactions in the
      rhizosphere should assist in the successful application of bacteria as biological
      control agents against fungal pathogens of plants, providing alternatives to
      chemicals in sustainable agriculture. Rhizoctonia solani is an important soil
      associated fungal pathogen and its chemical treatment is not feasible or
      economic. The genomes of the plant-associated bacteria Serratia proteamaculans S4
      and Serratia plymuthica AS13 have been sequenced, revealing genetic traits that
      may explain their diverse plant growth promoting activities and antagonistic
      interactions with R. solani. To understand the functional response of this
      pathogen to different bacteria and to elucidate whether the molecular mechanisms
      that the fungus exploits involve general stress or more specific responses, we
      performed a global transcriptome profiling of R. solani Rhs1AP anastomosis group
      3 (AG-3) during interaction with the S4 and AS13 species of Serratia using RNA
      seq. RESULTS: Approximately 104,504 million clean 75-100 bp paired-end reads were
      obtained from three libraries, each in triplicate (AG3-Control, AG3-S4 and AG3
      AS13). Transcriptome analysis revealed that approximately 10% of the fungal
      transcriptome was differentially expressed during challenge with Serratia. The
      numbers of S4- and AS13-specific differentially expressed genes (DEG) were 866
      and 292 respectively, while there were 1035 common DEGs in the two treatment
      groups. Four hundred and sixty and 242 genes respectively had values of log2 fold
      change > 3 and for further analyses this cut-off value was used. Functional
      classification of DEGs based on Gene Ontology enrichment analysis and on KEGG
      pathway annotations revealed a general shift in fungal gene expression in which
      genes related to xenobiotic degradation, toxin and antioxidant production,
      energy, carbohydrate and lipid metabolism and hyphal rearrangements were
      subjected to transcriptional regulation. CONCLUSIONS: This RNA-seq profiling
      generated a novel dataset describing the functional response of the phytopathogen
      R. solani AG3 to the plant-associated Serratia bacteria S4 and AS13. Most genes
      were regulated in the same way in the presence of both bacterial isolates, but
      there were also some strain-specific responses. The findings in this study will
      be beneficial for further research on biological control and in depth exploration
      of bacterial-fungal interactions in the rhizosphere.

PMID- 26296339
TI  - Associations between parental chronic pain and self-esteem, social competence,
      and family cohesion in adolescent girls and boys--family linkage data from the
      HUNT study.
AB  - BACKGROUND: Parental chronic pain has been associated with adverse outcomes in
      offspring. However, knowledge on individual and family resilience factors in
      adolescent offspring of chronic pain sufferers is scarce. This study thus aimed
      to investigate the associations between parental chronic pain and self-esteem,
      social competence, and family cohesion levels reported by adolescent girls and
      boys. METHODS: Based on cross-sectional surveys from the Nord Trondelag Health
      Study (the HUNT 3 study), the study used independent self-reports from
      adolescents aged 13 to 18 years (n = 3227) and their parents and conducted
      separate linear regression analyses for girls and boys. RESULTS: Concurrent
      maternal and paternal chronic pain was associated with reduced self-esteem,
      social competence, and family cohesion in girls. Moreover, maternal chronic pain
      was associated with higher social competence in boys and reduced self-esteem in
      girls. The majority of the observed associations were significantly different
      between girls and boys. Paternal chronic pain was not found to be associated with
      child outcomes. CONCLUSIONS: The findings indicate that the presence of both
      maternal and paternal chronic pain could be a potential risk factor for lower
      levels of individual and family resilience factors reported by girls. Further
      research on the relationship between parental pain and sex-specific offspring
      characteristics, including positive resilience factors, is warranted. The study
      demonstrates the importance of targeting the entire family in chronic pain care.

PMID- 26296340
TI  - Dose escalation studies with caspofungin against Candida glabrata.
AB  - Echinocandins are recommended as first-line agents against invasive fungal
      infections caused by Candida glabrata, which still carry a high mortality rate.
      Dose escalation of echinocandins has been suggested to improve the clinical
      outcome against C. glabrata. To address this possibility, we performed in vitro
      and in vivo experiments with caspofungin against four WT C. glabrata clinical
      isolates, a drug-susceptible ATCC 90030 reference strain and two echinocandin
      resistant strains with known FKS mutations. MIC values for the clinical isolates
      in RPMI 1640 were <= 0.03 mg l(-1 ) but increased to 0.125-0.25 mg l(-1 )in RPMI
      1640+50% serum. In RPMI 1640+50% serum, the replication of C. glabrata was weaker
      than in RPMI 1640.Caspofungin in RPMI 1640 at 1 and 4 mg l(-1) showed a
      fungicidal effect within 7 h against three of the four clinical isolates but was
      only fungistatic at 16 and 32 mg l(-1) (paradoxically decreased killing
      activity). In RPMI 1640+50% serum, caspofungin at >= 1 mg l(-1) was rapidly
      fungicidal (within 3.31 h) against three of the four isolates. In a profoundly
      neutropenic murine model, all caspofungin doses (1, 2, 3, 5 and 20 mg kg(-1)
      daily) decreased the fungal tissue burdens significantly (P < 0.05-0.001) without
      statistical differences between doses, but the mean fungal tissue burdens never
      fell below 105 cells (g tissue)(-1). The echinocandin-resistant strains were
      highly virulent in animal models and all doses were ineffective. These results
      confirm the clinical experience that caspofungin dose escalation does not improve
      efficacy.

PMID- 26296341
TI  - Aureimonas glaciistagni sp. nov., isolated from a melt pond on Arctic sea ice.
AB  - A Gram-staining-negative, motile, aerobic and rod-shaped bacterial strain, PAMC
      27157T, was isolated from a melt pond on sea ice in the Chukchi Sea. Phylogenetic
      analysis of the 16S rRNA gene sequence of strain PAMC 27157T revealed an
      affiliation to the genus Aureimonas with the closest sequence similarity (96.2 %)
      to that of Aureimonas phyllosphaerae. Strain PAMC 27157T grew optimally at 30 
      degrees C and pH 7.0 in the presence of 3.5 % (w/v) NaCl. The major polar lipids
      were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine,
      phosphatidylcholine, phosphatidylmonomethylethanolamine,
      sulfoquinovosyldiacylglycerol and an unidentified aminolipid. The major cellular
      fatty acid was summed feature 8 (C18 : 1omega7c and/or C18 : 1omega6c, 83.1 %)
      and the major respiratory quinone was Q-10. The genomic DNA G+C content was 69.1
      mol%. The combined phylogenetic, phenotypic and chemotaxonomic data showed that
      strain PAMC 27157T could be clearly distinguished from species of the genus
      Aureimonas with validly published names. Thus, strain PAMC 27157T should be
      classified as representing a novel species in the genus Aureimonas, for which the
      name Aureimonas glaciistagni sp. nov. is proposed. The type strain is PAMC 27157T
      ( = KCCM 43049T = JCM 30183T). 

PMID- 26296342
TI  - Sphingomonas vulcanisoli sp. nov., isolated from soil of a lava forest.
AB  - A Gram-stain-negative, non-motile, yellow-pigmented and rod-shaped bacterial
      strain, designated SN6-13T, was isolated from soil of the Gotjawal, lava forest,
      located in Jeju, Republic of Korea. Cells of strain SN6-13T were oxidase- and
      catalase-positive. The isolate contained Q-10 as the predominant isoprenoid
      quinone, summed feature 8 (C18 : 1omega7c and/or C18 : 1omega6c) and C16 : 0 as
      the major fatty acids, sym-homospermidine as the major polyamine and
      diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine,
      phosphatidylcholine, sphingoglycolipid, ninhydrinphosphatidylglycerol and two
      unidentified aminophospholipids as the polar lipids. The DNA G+C content was 64.6
      mol%. In phylogenetic analyses based on 16S rRNA gene sequencing, strain SN6-13T
      was most closely related to Sphingomonas laterariae LNB2T (95.4 % sequence
      similarity) and formed a separate lineage in the genus Sphingomonas. Based on
      phenotypic, chemotaxonomic and phylogenetic characteristics, it is concluded that
      strain SN6-13T represents a novel species of the genus Sphingomonas, for which
      the name Sphingomonas vulcanisoli sp. nov. is proposed. The type strain is SN6
      13T ( = KCTC 42454T = CECT 8804T). 

PMID- 26296343
TI  - Paracoccus angustae sp. nov., isolated from soil.
AB  - A Gram-stain-negative, coccus-shaped, aerobic bacterium, strain E6T, was isolated
      from soil. 16S rRNA gene sequence analysis revealed a cluster containing strain
      E6T and Paracoccus sediminis CMB17T (the highest 16S rRNA gene similarity of 97.2
      %). The other strains investigated showed 16S rRNA gene sequence similarities of
      less than 97 % to strain E6T. The DNA-DNA relatedness between strain E6T and P.
      sediminis DSM 26170T was 59.2 %. Strain E6T also shows some differences compared
      with other Paracoccus strains such as motility and inability to utilize lactate
      and propionate as sole carbon sources. The major fatty acids of strain E6T were
      C18 : 1omega7c and C18 : 0 and ubiquinone-10 was the only respiratory quinone.
      Strain E6T had diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine,
      an unknown aminolipid and an unknown glycolipid as major polar lipids. The
      genomic DNA G+C content was 68.1 mol%. On the basis of phenotypic and genotypic
      characteristics, strain E6T is concluded to represent a novel species of the
      genus Paracoccus, for which the name Paracoccus angustae sp. nov. is proposed.
      The type strain is E6T ( = KCTC 42473T = CCTCC AB 2015056T).

PMID- 26296344
TI  - Reliability of molecular host-identification methods for ticks: an experimental
      in vitro study with Ixodes ricinus.
AB  - BACKGROUND: Reliable information on host use by arthropod vectors is required to
      study pathogen transmission ecology and to predict disease risk. Direct
      observation of host use is often difficult or impossible and indirect methods are
      therefore necessary. However, the reliability of currently available methods to
      identify the last host of blood-feeding arthropods has not been evaluated, and
      may be particularly problematic for ticks because host blood has been digested at
      capture. Biases in host detection may lead to erroneous conclusions on both
      vector ecology and pathogen circulation. METHODS: Here, we experimentally tested
      for biases in host detection using the generalist three-host tick Ixodes ricinus
      as a model system. We fed ticks using an artificial feeding system and amplified
      blood meal traces post-moult (i.e., in the succeeding unfed life stage) via both
      a quantitative real-time polymerase chain reaction assay and a reverse line
      blotting method. We then experimentally tested for three types of biases in host
      detection: 1) time post-moult, 2) tick life stage and 3) host type (non-nucleated
      mammal blood versus nucleated avian blood), and compared these biases between the
      two molecular methods. RESULTS: Our results show that all three factors can
      influence host detection in ticks but not necessarily in the expected way.
      Although host detection rates decreased with time post-moult, mammal blood tended
      to be more readily detected than bird blood. Tick life stage was also an
      important factor; detection was higher in nymphs than in adults and, in some
      cases, remnants from both larval and nymphal blood meals could be detected in the
      adult stage. These biases were similar for the two detection techniques.
      CONCLUSIONS: We show that different factors associated with questing ticks may
      influence our ability to correctly infer previous host use and that these factors
      may bias inferences from field-based studies. As these biases may be common to
      other vector-borne disease systems, their implications for our understanding of
      vector ecology and disease transmission require more explicit consideration.

PMID- 26296345
TI  - Developing a high-throughput screening method for threonine overproduction based
      on an artificial promoter.
AB  - BACKGROUND: L-Threonine is an important amino acid for animal feed. Though the
      industrial fermentation technology of threonine achieved a very high level, there
      is still significant room to further improve the industrial strains. The
      biosensor-based high-throughput screening (HTS) technology has demonstrated its
      powerful applications. Unfortunately, for most of valuable fine chemicals such as
      threonine, a HTS system has not been established mainly due to the absence of a
      suitable biosensor. In this study, we developed a HTS method to gain high
      yielding threonine-producing strains. RESULTS: Novel threonine sensing promoters
      including cysJp and cysHp were discovered by proteomic analyses of Escherichia
      coli in response to extracellular threonine challenges. The HTS method was
      constructed using a device composed of the fused cysJp and cysHp as a promoter
      and a linked enhanced green fluorescent protein gene as a reporter. More than 400
      strains were selected with fluorescence activated cell sorting technology from a
      library of 20 million mutants and tested within 1 week. Thirty-four mutants have
      higher productivities than the starting industrial producer. One mutant produced
      17.95 % more threonine in a 5-L jar fermenter. CONCLUSIONS: This method should
      play a functional role for continuous improvement of threonine industry.
      Additionally, the threonine sensor construction using promoters obtained by
      proteomics analyses is so convenient that it would be easily extended to develop
      HTS models for other biochemicals.

PMID- 26296346
TI  - Limibacillus halophilus gen. nov., sp. nov., a moderately halophilic bacterium in
      the family Rhodospirillaceae isolated from reclaimed land.
AB  - A Gram-stain-negative, aerobic, non-motile, non-spore-forming and short rod
      shaped bacterial strain, designated CAU 1121(T), was isolated from reclaimed land
      in the Republic of Korea and its taxonomic position was investigated using a
      polyphasic approach. The bacterium grew optimally at 37  degrees C, at pH 6.5 and
      in the presence of 2% (w/v) NaCl. Based on 16S rRNA gene sequence similarity, the
      novel isolate belonged to the family Rhodospirillaceae within the class
      Alphaproteobacteria and formed an independent lineage within the evolutionary
      radiation encompassed by the phylum Proteobacteria. Strain CAU 1121(T) exhibited
      very low levels of 16S rRNA gene sequence similarity with its phylogenetic
      neighbours Pelagibius litoralis (similarity, 92.5%), Fodinicurvata fenggangensis
      (similarity, 91.4%), Fodinicurvata sediminis (similarity, 90.7%) and Tistlia
      consotensis (similarity, 91.0%). Strain CAU 1121(T) contained ubiquinone-10 as
      the only respiratory quinone and C18 : 1omega7c as the major cellular fatty acid.
      The DNA G+C content of the strain was 65 mol%. On the basis of phylogenetic
      inference, and physiological and chemotaxonomic data, it is proposed that strain
      CAU 1121(T) represents a novel genus and novel species in the family
      Rhodospirillaceae, for which the name Limibacillus halophilus gen. nov., sp. nov.
      is suggested. The type strain is CAU 1121(T) ( = KCTC 42420(T) = CECT 8803(T) =
      NBRC 110928(T)).

PMID- 26296347
TI  - The status of the species Shewanella irciniae Lee et al. 2006. Request for an
      opinion.
AB  - During a taxonomic study in describing a novel species of the genus Shewanella
      from a mangrove ecosystem, it was found that the type strain Shewanella irciniae
      was not available from the Japan Collection of Microorganisms (JCM) and the type
      strain received from the Agricultural Research Service (ARS) culture collection
      and from the author who described this species were found to be members of the
      genus Brevibacillus based on 16S rRNA gene sequence analysis. Therefore, this
      species cannot be included in any further scientific studies. It is therefore
      proposed that the Judicial Commission of the International Committee of
      Systematics of Prokaryotes place the name Shewanella irciniae on the list of
      rejected names, if a suitable replacement for the type strain is not found or a
      neotype strain is not proposed within two years following the publication of this
      Request for an Opinion. 

PMID- 26296348
TI  - Evaluation of factors affecting real-time PCR performance for diagnosis of
      Entamoeba histolytica and Entamoeba dispar in clinical stool samples.
AB  - Although PCR offers the potential for sensitive detection of parasites there are
      several pitfalls for optimal performance, especially when DNA is extracted from a
      complex sample material such as stool. With the aid of a sensitive inhibitor
      control in a duplex real-time PCR (qPCR) for identification of Entamoeba
      histolytica and Entamoeba dispar we have evaluated factors that influenced the
      performance of the qPCR and have suggested a rationale to be used in the analysis
      of clinical samples. Pre-PCR processing was found to be of outmost importance for
      an optimal amplification since inhibitors caused false-negative results when
      higher amounts of sample were used. Stool sampling with a flocked swab (ESwab,
      Copan), yielding on average 173 mg, gave positive qPCR results in samples with
      cysts of E. dispar that were negative in serially diluted stool samples. The
      degree of inhibition found varied between samples and was not an on-off
      phenomenon. Even low-grade inhibition, shown as an increase of two cycles in the
      qPCR for the inhibitor control, could lead to false negativity in samples with
      low amounts of parasites. Lack of amplification in the qPCR due to inhibition
      could be overcome by dilution of the extracted DNA by 1/10-1/20. We also describe
      the use of guanidinium thiocyanate buffer for transport and storage of samples as
      well as a time-saving semi-automated DNA extraction method in an Arrow instrument
      (Nordiag) preceded by bead beating.

PMID- 26296349
TI  - Amino acid substitutions in the transcriptional regulator CbbR lead to
      constitutively active CbbR proteins that elevate expression of the cbb CO2
      fixation operons in Ralstonia eutropha (Cupriavidus necator) and identify regions
      of CbbR necessary for gene activation.
AB  - CbbR is a LysR-type transcriptional regulator that activates expression of the
      operons containing (cbb) genes that encode the CO2 fixation pathway enzymes in
      Ralstonia eutropha (Cupriavidus necator) under autotrophic growth conditions. The
      cbb operons are stringently downregulated during chemoheterotrophic growth on
      organic acids such as malate. CbbR constitutive proteins (CbbR*s), typically with
      single amino acid substitutions, were selected and isolated that activate
      expression of the cbb operons under chemoheterotrophic growth conditions. A large
      set of CbbR*s from all major domains of the CbbR molecule were identified, except
      for the DNA-binding domain. The level of gene expression conferred for many of
      these CbbR*s under autotrophic growth was greater than that conferred by wild
      type CbbR. Several of these CbbR*s increase transcription two- to threefold more
      than wild-type CbbR. One particular CbbR*, a truncated protein, was useful in
      identifying the regions of CbbR that are necessary for transcriptional activation
      and, by logical extension, necessary for interaction with RNA polymerase. The
      reductive assimilation of carbon via CO2 fixation is an important step in the
      cost-effective production of useful biological compounds. Enhancing CO2 fixation
      in Ralstonia eutropha through greater transcriptional activation of the cbb
      operons could prove advantageous, and the use of CbbR*s is one way to enhance
      product formation. 

PMID- 26296350
TI  - Characterization of lethal dengue virus type 4 (DENV-4) TVP-376 infection in mice
      lacking both IFN-alpha/beta and IFN-gamma receptors (AG129) and comparison with
      the DENV-2 AG129 mouse model.
AB  - Dengue is a mosquito-borne disease caused by four related but distinct dengue
      viruses, DENV-1 to DENV-4. Dengue is endemic in most tropical countries, and over
      a third of the world's population is at risk of being infected. Although the
      global burden is high, no vaccine or antiviral is licensed to combat this
      disease. An obstacle complicating dengue research is the lack of animal challenge
      models that mimic human disease. Advances in immunocompromised murine infection
      models resulted in development of lethal DENV-2, DENV-3 and DENV-4 models in
      AG129 mice, which are deficient in both the IFN-alpha/beta receptor (IFN
      alpha/betaR) and the IFN-gamma receptor (IFN-gammaR). These models mimic features
      of dengue disease in humans. Here, we characterized lethal infection of AG129
      mice by DENV-4 strain TVP-376 and found that AG129 mice developed clinical signs
      of illness and high viral loads in multiple tissues and succumbed 5 days after
      infection. Moreover, the splenic and hepatic histopathology of TVP-376-infected
      mice demonstrated the presence of cell activation and destruction of tissue
      architecture. Furthermore, infected mice had heightened levels of circulating
      cytokines. Comparison of the virulence phenotypes of DENV-4 strain TVP-376 and
      DENV-2 strain D2S10 revealed that TVP-376-induced mortality occurred in the
      absence of both IFN-alpha/betaR and IFN-gammaR signalling, but not with intact
      signalling from the IFN-gammaR, whereas D2S10 required the absence of IFN
      alpha/betaR signalling only, indicating that it is more virulent than TVP-376. In
      conclusion, TVP-376 is lethal in AG129 mice, and this model provides a useful
      platform to investigate vaccine candidates and antivirals against DENV-4. 

PMID- 26296351
TI  - Crassaminicella profunda gen. nov., sp. nov., an anaerobic marine bacterium
      isolated from deep-sea sediments.
AB  - A novel, anaerobic, chemo-organotrophic bacterium, designated strain Ra1766H(T),
      was isolated from sediments of the Guaymas basin (Gulf of California, Mexico)
      taken from a depth of 2002  m. Cells were thin, motile, Gram-stain-positive,
      flexible rods forming terminal endospores. Strain Ra1766H(T) grew at temperatures
      of 25-45  degrees C (optimum 30  degrees C), pH 6.7-8.1 (optimum 7.5) and in a
      salinity of 5-60 g l(-1) NaCl (optimum 30 g l(-1)). It was an obligate
      heterotrophic bacterium fermenting carbohydrates (glucose and mannose) and
      organic acids (pyruvate and succinate). Casamino acids and amino acids
      (glutamate, aspartate and glycine) were also fermented. The main end products
      from glucose fermentation were acetate, butyrate, ethanol, H2 and CO2. Sulfate,
      sulfite, thiosulfate, elemental sulfur, fumarate, nitrate, nitrite and Fe(III)
      were not used as terminal electron acceptors. The predominant cellular fatty
      acids were C14  : 0, C16 : 1omega7, C16 : 1omega7 DMA and C16 : 0. The main polar
      lipids consisted of phosphatidylglycerol, diphosphatidylglycerol,
      phosphatidylethanolamine and phospholipids. The G+C content of the genomic DNA
      was 33.7 mol%. Phylogenetic analysis of the 16S rRNA gene sequence indicated that
      strain Ra1766H(T) was affiliated to cluster XI of the order Clostridiales, phylum
      Firmicutes. The closest phylogenetic relative of Ra1766H(T) was Geosporobacter
      subterraneus (94.2% 16S rRNA gene sequence similarity). On the basis of
      phylogenetic inference and phenotypic properties, strain Ra1766H(T) ( = DSM
      27501(T) = JCM 19377(T)) is proposed to be the type strain of a novel species of
      a novel genus, named Crassaminicella profunda.

PMID- 26296352
TI  - Process Evaluation of a Comprehensive Supermarket Intervention in a Low-Income
      Baltimore Community.
AB  - Supermarket-based interventions are one approach to improving the local food
      environment and reducing obesity and chronic disease in low-income populations.
      We implemented a multicomponent intervention that aimed to reduce environmental
      barriers to healthy food purchasing in a supermarket in Southwest Baltimore. The
      intervention, Eat Right-Live Well! used: shelf labels and in-store displays
      promoting healthy foods, sales and promotions on healthy foods, in-store taste
      tests, increasing healthy food products, community outreach events to promote the
      intervention, and employee training. We evaluated program implementation through
      store environment, taste test session, and community event evaluation forms as
      well as an Employee Impact Questionnaire. The stocking, labeling, and advertising
      of promoted foods were implemented with high and moderate fidelity. Taste test
      sessions were implemented with moderate reach and low dose. Community outreach
      events were implemented with high reach and dose. Supermarket employee training
      had no significant impact on employees' knowledge, self-efficacy, or behavioral
      intention for helping customers with healthy purchasing or related topics of
      nutrition and food safety. In summary, components of this intervention to promote
      healthy eating were implemented with varying success within a large supermarket.
      Greater participation from management and employees could improve implementation.

PMID- 26296353
TI  - High blood pressure is warning sign in pregnant women with new headaches, study
      finds.

PMID- 26296354
TI  - Morphological, Molecular, and Hormonal Basis of Limb Regeneration across
      Pancrustacea.
AB  - Regeneration is a developmental process that allows an organism to re-grow a lost
      body part. Historically, the most studied aspect of limb regeneration across
      Pancrustacea is its morphological basis and its dependence on successful molting.
      Although there are distinct morphological differences in regeneration processes
      between insects and crustaceans, in both groups the phenomenon is initiated via
      formation of a blastema, followed by proliferation, dedifferentiation, and
      redifferentiation of blastemal cells to generate a functional limb. In recent
      years, with the availability of sequence data and tools to manipulate gene
      expression, the emphasis of this field has shifted toward the genetic basis of
      limb regeneration. Among insects this focus is on genes that are known to be
      required during the development of legs in embryos. RNA interference-mediated
      functional studies conducted during regeneration of imaginal discs of Drosophila
      melanogaster, and nymphal legs of Gryllus bimaculatus reveal that several
      conserved pathways and transcription factors (Wingless, Decapentaplegic,
      Hedgehog, Dachshund) are required for successful regeneration. In contrast to
      studies on the regeneration of insects' limbs, work on crustaceans has focused on
      the hormonal basis of the re-growth of limbs. Regeneration in decapods, like Uca
      pugilator and Gecarcinus lateralis, occurs in discrete phases of growth in tandem
      with the stages of the molt cycle. Recent studies have shown that ecdysteroid
      hormone signaling is necessary for blastemal proliferation. Although the current
      research emphases of limb regeneration in insect and crustacean are fairly
      distinct, the results generated by functional studies of a wide array of
      regeneration genes will be beneficial for generating testable regeneration
      models. 

PMID- 26296355
TI  - Sustained Inhibition of HER3 and EGFR Is Necessary to Induce Regression of HER2
      Amplified Gastrointestinal Carcinomas.
AB  - PURPOSE: Preclinical studies in HER2-amplified gastrointestinal cancer models
      have shown that cotargeting HER2 with a monoclonal antibody and a small molecule
      is superior to monotherapy with either inhibitor, but the underlying cooperative
      mechanisms remain unexplored. We investigated the molecular underpinnings of this
      synergy to identify key vulnerabilities susceptible to alternative therapeutic
      opportunities. EXPERIMENTAL DESIGN: The phosphorylation/activation of HER2, HER3,
      EGFR (HER receptors), and downstream transducers was evaluated in HER2
      overexpressing colorectal and gastric cancer cell lines by Western blotting
      and/or multiplex phosphoproteomics. The in vivo outcome of antibody-mediated HER2
      blockade by trastuzumab, reversible HER2 inhibition by lapatinib, and
      irreversible HER2 inhibition by afatinib was assessed in patient-derived
      tumorgrafts and cell-line xenografts by monitoring tumor growth curves and by
      using antibody-based proximity assays. RESULTS: Trastuzumab monotherapy reduced
      HER3 phosphorylation, with minor consequences on downstream transducers.
      Lapatinib alone acutely inhibited all HER receptors and effectors but led to
      delayed rephosphorylation of HER3 and EGFR and partial restoration of ERK and AKT
      activity. When combined with lapatinib, trastuzumab prevented HER3/EGFR
      reactivation and caused prolonged inhibition of ERK/AKT. Afatinib alone was also
      very effective in counteracting the reinstatement of HER3, EGFR, and downstream
      signaling activation. In vivo, the combination of trastuzumab and lapatinib-or,
      importantly, monotherapy with afatinib-resulted in overt tumor shrinkage.
      CONCLUSIONS: Only prolonged inhibition of HER3 and EGFR, achievable by dual
      blockade with trastuzumab and lapatinib or irreversible HER2 inhibition by single
      agent afatinib, led to regression of HER2-amplified gastrointestinal carcinomas.
      Clin Cancer Res; 21(24); 5519-31. (c)2015 AACR.

PMID- 26296356
TI  - Characterization of the physicochemical properties of phospholipid vesicles
      prepared in CO2/water systems at high pressure.
AB  - Phospholipid vesicles were prepared by the nonsolvent method using high-pressure
      CO2/water systems. The membrane properties of vesicles prepared at different
      pressures and temperatures were mainly characterized based on analysis of the
      membrane fluidity and membrane polarity, using the fluorescent probes 1,6
      diphenyl-1,3,5-hexatriene and 6-dodecanoyl-N,N-dimethyl-2-naphthylamine,
      respectively. The CO2(liquid)/water(liquid) and the
      CO2(supercritical)/water(liquid) two-phase (heterogeneous) systems resulted in
      the formation of vesicles with high yield (ca. 85%-88%). The membrane fluidity
      and polarity of the vesicles were similar to those of liposomes prepared by the
      conventional method. It is suggested that high-pressure CO2 can be used to form
      an appropriate hydrophobic-hydrophilic interface where phospholipid molecules as
      a self-assembled membrane. 

PMID- 26296357
TI  - Stability of biodegradable waterborne polyurethane films in buffered saline
      solutions.
AB  - The stability of polyurethane (PU) is of critical importance for applications
      such as in coating industry or as biomaterials. To eliminate the environmental
      concerns on the synthesis of PU which involves the use of organic solvents, the
      aqueous-based or waterborne PU (WBPU) has been developed. WBPU, however, may be
      unstable in an electrolyte-rich environment. In this study, the authors reported
      the stability of biodegradable WBPU in the buffered saline solutions evaluated by
      atomic force microscopy (AFM). Various biodegradable WBPU films were prepared by
      spin coating on coverslip glass, with a thickness of ~300 nm. The surface AFM
      images of poly(epsilon-caprolactone) (PCL) diol-based WBPU revealed nanoglobular
      structure. The same feature was observed when 20% molar of the PCL diol soft
      segment was replaced by polyethylene butylenes adipate diol. After hydration in
      buffered saline solutions for 24 h, the surface domains generally increased in
      sizes and became irregular in shape. On the other hand, when the soft segment was
      replaced by 20% poly(l-lactide) diol, a meshlike surface structure was
      demonstrated by AFM. When the latter WBPU was hydrated, the surface domains
      appeared to be disconnected. Results from the attenuated total reflectance
      infrared spectroscopy and x-ray photoelectron spectroscopy indicated that the
      surface chemistry of WBPU films was altered after hydration. These changes were
      probably associated with the neutralization of carboxylate by ions in the saline
      solutions, resulting in the rearrangements of soft and hard segments and causing
      instability of the WBPU. 

PMID- 26296358
TI  - Immediate effects of acupuncture on tongue pressure including swallowing reflex
      latency in Parkinson's disease.
AB  - BACKGROUND: It is important to evaluate tongue function in terms of its clinical
      implications for swallowing ability. Motor dysfunction and loss of coordination
      of the tongue are frequently seen, and this influences the oral and pharyngeal
      phases of swallowing. The purpose of this pilot study was to evaluate the effect
      of a single acupuncture treatment for tongue pressure in Parkinson's disease.
      METHODS: A total of 13 patients, aged 57- 84 years, were recruited. Tongue
      pressure was measured using a tongue pressure manometer. Furthermore, swallowing
      reflex latency was measured in 3 of the 13 patients. RESULTS: Significant changes
      were seen after acupuncture in mean tongue pressure, which increased from 23.1 to
      26.7 kPa (p<0.01). Reductions were seen after acupuncture in mean swallowing
      reflex latency (from 5.2 to 4.6 s for first saliva swallow; from 19.9 to 15.7 s
      for second saliva swallow; and from 10.4 to 5.7 s for third saliva swallow(s)).
      CONCLUSIONS: Our study's findings suggest that acupuncture may be useful for
      improving oral cavity function, but further controlled trials are needed.

PMID- 26296359
TI  - Effects of acupuncture on cortical expression of Wnt3a, beta-catenin and Sox2 in
      a rat model of traumatic brain injury.
AB  - OBJECTIVE: To observe the effects of acupuncture treatment on the expression of
      Wnt/beta-catenin signalling pathway-related genes (Wnt3a, beta-catenin and Sox2)
      in the injured cerebral cortex of rats with traumatic brain injury (TBI).
      METHODS: A controlled impact model of TBI was established using Feeney's free
      drop method. Seventy-eight Sprague-Dawley rats were randomly divided into the
      following three groups: a normal group (n=18) that was left untreated; a model
      group (n=30) that received no treatment after TBI; and an acupuncture group
      (n=30) that received acupuncture (at LI4, GV20, GV26 and GV16) after TBI. Rats in
      each group were randomly and equally divided into 3-day, 7-day and 14-day
      subgroups according to the duration of therapy. Real-time fluorescence
      quantitative PCR (RT-qPCR) was used to measure mRNA expression of Wnt3a, beta
      catenin and Sox2. Western blots were performed to determine the expression levels
      of WNT3a, beta-Catenin and SOX2. RESULTS: Wnt3a mRNA was upregulated in the 7-day
      and 14-day acupuncture subgroups compared with the corresponding model subgroups
      (p<0.05). beta-catenin expression was significantly increased in the 7-day and 14
      day acupuncture subgroups compared with the corresponding model subgroups
      (p<0.01). In the 3-day and 7-day acupuncture subgroups, Sox2 expression was
      significantly higher than that in the normal and model groups (p<0.01 each). The
      levels of WNT3a, beta-catenin and SOX2 were generally consistent with the
      corresponding mRNA levels. CONCLUSIONS: Acupuncture exerts a regulatory effect on
      the Wnt/beta-catenin signalling pathway, which may in turn influence the
      proliferation and differentiation of endogenous neural stem cells.

PMID- 26296360
TI  - Lupus nephritis in Latin American patients: 10-year results from a single medical
      center in Argentina.
AB  - INTRODUCTION: Several studies have shown that Hispanic patients generally
      experience a worse renal prognosis than non-Hispanic white patients with lupus.
      To date, there is no report on American College of Rheumatology (ACR) renal
      response criteria (ACR-RRC) in patients from Latin America. OBJECTIVE: To
      evaluate treatment response in patients with proliferative and membranous lupus
      nephritis (LN) according to ACR-RRC. METHODS: A retrospective study (2001-2011)
      was performed in our hospital and the data collected included clinical
      information, renal assessment and immunological parameters. Details related to
      treatment received during induction and maintenance therapy were also recorded.
      RESULTS: The study included forty-three Latin American patients (37 women) from
      Argentina. Mean follow-up was 54 months. The regimen used for induction therapy
      included intravenous cyclophosphamide (IV-CYC) for six months in 36 patients and
      only seven received mycophenolate mofetil (MMF) given twice daily for a total
      dose of 2.5 +/- 0.5 grams a day. For the maintenance period, six patients
      continued with quarterly IV-CYC, 20 patients received MMF (1.5 +/- 0.5 grams a
      day) and 17 patients received azathioprine (AZA) 1.5 - 2 mg/kg/day. ACR-RRC
      observed after induction therapy was complete response in 19%, partial response
      in 9%, improvement in 42%, unchanged in 14%, and 16% had deterioration despite
      treatment. ACR-RRC observed after maintenance therapy was complete response in
      30%, partial response in 23%, improvement in 19%, unchanged in 16%, and 12% had
      deterioration. Relapse was observed in 11 patients (25%). Ten out of 11 cases
      (91%) who relapsed did not achieve a complete response at the end of the
      induction therapy. CONCLUSION: In Latin American patients from Argentina, only
      19% could achieve a complete response after induction therapy and 30% achieved a
      complete response after maintenance therapy. Failing to obtain a complete
      response after induction therapy was related to an increased risk of relapse
      during long-term follow-up in our study.

PMID- 26296361
TI  - The efficacy of add-on tacrolimus for minor flare in patients with systemic lupus
      erythematosus: a retrospective study.
AB  - OBJECTIVE: We have assessed the effectiveness of tacrolimus for minor flares in
      systemic lupus erythematosus (SLE) patients. METHODS: The medical records of 313
      patients were retrospectively reviewed over a period of seven years, from 2006 to
      2013. We enrolled patients with minor flare treated with add-on tacrolimus,
      without glucocorticoid (GC) intensification (tacrolimus group). Minor flare was
      defined as a >= 1-point increase in a total score between 3 and 11 in the SLE
      Disease Activity Index (SLEDAI). We enrolled as controls patients who were
      administered increased doses of GC for minor flare (GC group). All patients were
      followed for one year. The primary outcome measure was the proportion of
      responders. RESULTS: There were 14 eligible patients in the tacrolimus group and
      20 eligible patients in the GC group. The mean SLEDAI at flare tended to be
      higher in the tacrolimus group than in the GC group (7.5 vs. 6.2, p = 0.085). A
      mean dose of 1.6 mg tacrolimus/day was administered for flare, while the mean GC
      dose was 13.7 mg/day in the GC group. The proportion of responders was 86%
      (12/14) in the tacrolimus group and 75% (15/20) in the GC group (p = 0.67). The
      mean dose of GC at 12 months was higher in the GC group than in the tacrolimus
      group (9.7 mg/day vs. 7.1 mg/day, p < 0.05). Only one patient discontinued
      tacrolimus because of fatigue after three months. CONCLUSION: Adding tacrolimus
      without increasing the GC dose may provide an effective treatment option for
      minor flares in patients with SLE.

PMID- 26296363
TI  - Peril in perishing pericytes.

PMID- 26296362
TI  - Role of Tumor Pericytes in the Recruitment of Myeloid-Derived Suppressor Cells.
AB  - BACKGROUND: Pericytes are members of the tumor stroma; however, little is known
      about their origin, function, or interaction with other tumor components.
      Emerging evidence suggest that pericytes may regulate leukocyte transmigration.
      Myeloid-derived suppressor cells (MDSC) are immature myeloid cells with powerful
      inhibitory effects on T-cell-mediated antitumor reactivity. METHODS: We generated
      subcutaneous tumors in a genetic mouse model of pericyte deficiency (the pdgfb
      (ret/ret) mouse) and littermate control mice (n = 6-25). Gene expression profiles
      from 253 breast cancer patients (stage I-III) were evaluated for clinic
      pathological parameters and survival using Cox proportional hazard ratios (HRs)
      and 95% confidence intervals (CIs) based on a two-sided Wald test. RESULTS: We
      report that pericyte deficiency leads to increased transmigration of
      Gr1(+)/CD11b(+) cells in experimentally induced tumors. Pericyte deficiency
      produced defective tumor vasculature, resulting in a more hypoxic
      microenvironment promoting IL-6 upregulation in the malignant cells. Silencing IL
      6 expression in tumor cells attenuated the observed differences in MDSC
      transmigration. Restoring the pericyte coverage in tumors abrogated the increased
      MDSC trafficking to pericyte-deficient tumors. MDSC accumulation in tumors led to
      increases in tumor growth and in circulating malignant cells. Finally, gene
      expression analysis from human breast cancer patients revealed increased
      expression of the human MDSC markers CD33 and S100A9 with concomitant decreased
      expression of pericyte genes and was associated with poor prognosis (HR = 1.88,
      95% CI = 1.08 to 3.25, P = .03). CONCLUSIONS: Our data uncovers a novel paracrine
      interaction between tumor pericytes and inflammatory cells and delineates the
      cellular events resulting in the recruitment of MDSC to tumors. Furthermore, we
      propose for the first time a role for tumor pericytes in modulating the
      expression of immune mediators in malignant cells by promoting a hypoxic
      microenvironment.

PMID- 26296364
TI  - Ethnobotanical study of homegarden plants in Sebeta-Awas District of the Oromia
      Region of Ethiopia to assess use, species diversity and management practices.
AB  - BACKGROUND: Homegardens in Ethiopia are currently facing different threats mainly
      due genetic erosion, loss of traditional knowledge on their use and management
      and drought. On the other hand, research and documentation works on homegardens
      in the country are very limited. There is no previous report indicating conduct
      of ethnobotanical study on homegardens in selected study district. The present
      study thus attempted to document knowledge on uses and management practices of
      homegardens by people in study district. METHODS: The study was conducted in
      Sebeta-Awas District, Southwestern Shewa Zone of Oromia Region, Ethiopia, between
      March and September 2009 to assess use, species diversity and conservation status
      of homegardens in the District. Data were collected using semi-structured
      interviews as well as through homegarden visits, market surveys and different
      ranking exercises. For the semi-structured interviews, 42 homegarden owners were
      selected randomly from seven sampled kebeles (smallest administrative units in
      Ethiopia), six from each kebele. For different ranking exercises, 14 informants
      (10 males and 4 females) were sampled using convenient sampling method from among
      homegarden owners that already participated in semi-structured interviews.
      RESULTS: In total, 113 plant species belonging to 46 families were recorded from
      the study area, of which 45 (39.8%) were herbs, 34 (30.1%) were trees, 26 (23.0%)
      were shrubs and 8 (7.1%) were climbers. Fabaceae had the highest number of
      species, followed by the families Asteraceae, Lamiaceae and Solanaceae. The cash
      crops Catha edulis, Rhamnus prinoides and Ruta chalepensis were the most
      frequently encountered homegarden plants. Cupressus lusitanica, Eucalyptus
      camaldulensis and Faidherbia albida were the most abundant tree species that had
      the highest densities of occurrence. Of the recorded plant species, 25% were used
      as sources of food, 13% as medicine and 10% as household tools. CONCLUSION: It
      can be concluded that homegardens in the study area are rich in crops and,
      therefore, significantly contribute to the agrobiodiversity of the study
      District, in particular, and Ethiopia, in general.

PMID- 26296365
TI  - PA-X is a virulence factor in avian H9N2 influenza virus.
AB  - H9N2 influenza viruses have been circulating worldwide in multiple avian species,
      and regularly infect pigs and humans. Recently, a novel protein, PA-X, produced
      from the PA gene by ribosomal frameshifting, was demonstrated to be an
      antivirulence factor in pandemic 2009 H1N1, highly pathogenic avian H5N1 and 1918
      H1N1 viruses. However, a similar role of PA-X in the prevalent H9N2 avian
      influenza viruses has not been established. In this study, we compared the
      virulence and cytopathogenicity of H9N2 WT virus and H9N2 PA-X-deficient virus.
      Loss of PA-X in H9N2 virus reduced apoptosis and had a marginal effect on progeny
      virus output in human pulmonary adenocarcinoma (A549) cells. Without PA-X, PA was
      less able to suppress co-expressed GFP in human embryonic kidney 293T cells.
      Furthermore, absence of PA-X in H9N2 virus attenuated viral pathogenicity in
      mice, which showed no mortality, reduced progeny virus production, mild-to-normal
      lung histopathology, and dampened proinflammatory cytokine and chemokine
      response. Therefore, unlike previously reported H1N1 and H5N1 viruses, we show
      that PA-X protein in H9N2 virus is a pro-virulence factor in facilitating viral
      pathogenicity and that the pro- or antivirulence role of PA-X in influenza
      viruses is virus strain-dependent. 

PMID- 26296366
TI  - The clinical utility of the tic-related obsessive-compulsive disorder diagnostic
      specifier.

PMID- 26296367
TI  - Association of different forms of bullying victimisation with adolescents'
      psychological distress and reduced emotional wellbeing.
AB  - OBJECTIVE: The frequency and emotional response to bullying victimisation are
      known to be associated with adolescent mental ill health. A potentially important
      under-investigated factor is the form of bullying. Four common forms of bullying
      behaviours are name-calling, physical threats or harm, rumour spreading and
      social exclusion. To more comprehensively understand bullying victimisation in
      adolescence, we examined the association of all three factors (frequency,
      emotional response, form) to psychological distress and emotional wellbeing.
      METHOD: A stratified, random sample of adolescents (n = 10, 273; mean age = 14.33
      years, standard deviation = 1.68 years) completed validated measures of bullying
      victimisation (Gatehouse Bullying Questionnaire), psychological distress (K10)
      and emotional wellbeing (Mental Health Inventory) in classroom time. Associations
      between the form of bullying victimisation and mental health outcomes were
      examined. RESULTS: Adolescents reported a high prevalence of all four forms of
      bullying: teased or called names (30.6%), rumour spreading (17.9%), social
      exclusion (14.3%) and physical threats or harm (10.7%). Victimisation was
      independently associated with significantly higher levels of psychological
      distress and reduced levels of emotional wellbeing for all forms of bullying. In
      particular, social exclusion had a strong association with mental ill health.
      Adolescents who experienced frequent bullying that was upsetting reported higher
      psychological distress and reduced emotional wellbeing. CONCLUSION: Different
      forms of bullying victimisation were independently associated with psychological
      distress and reduced emotional wellbeing. In particular, frequent and upsetting
      social exclusion requires a targeted and measured response by school communities
      and health practitioners.

PMID- 26296368
TI  - Using the Delphi expert consensus method in mental health research.
AB  - OBJECTIVE: The article gives an introductory overview of the use of the Delphi
      expert consensus method in mental health research. It explains the rationale for
      using the method, examines the range of uses to which it has been put in mental
      health research, and describes the stages of carrying out a Delphi study using
      examples from the literature. METHOD: To ascertain the range of uses, a
      systematic search was carried out in PubMed. The article also examines the
      implications of 'wisdom of crowds' research for how to conduct Delphi studies.
      RESULTS: The Delphi method is a systematic way of determining expert consensus
      that is useful for answering questions that are not amenable to experimental and
      epidemiological methods. The validity of the approach is supported by 'wisdom of
      crowds' research showing that groups can make good judgements under certain
      conditions. In mental health research, the Delphi method has been used for making
      estimations where there is incomplete evidence (e.g. What is the global
      prevalence of dementia?), making predictions (e.g. What types of interactions
      with a person who is suicidal will reduce their chance of suicide?), determining
      collective values (e.g. What areas of research should be given greatest
      priority?) and defining foundational concepts (e.g. How should we define
      'relapse'?). A range of experts have been used in Delphi research, including
      clinicians, researchers, consumers and caregivers. CONCLUSION: The Delphi method
      has a wide range of potential uses in mental health research.

PMID- 26296369
TI  - Glycosylation-dependent interaction between CD69 and S100A8/S100A9 complex is
      required for regulatory T-cell differentiation.
AB  - Cluster of differentiation (CD)69 is a leukocyte activation receptor involved in
      the maintenance of immune homeostasis and is positively selected in activated
      regulatory T (Treg) cells, implicating its role during Treg-cell differentiation.
      By RNA interference, we show that CD69 is not sufficient to support the
      conversion of CD4(+) naive T cells into Treg cells, whereas it does that of human
      peripheral blood mononuclear cells (hPBMCs) (P < 0.01), suggesting that a ligand
      receptor interaction is required for CD69 function. Using immunoprecipitation and
      mass spectrometry, we identified the S100A8/S100A9 complex as the natural ligand
      of CD69 in hPBMCs. CD69 specifically associates with S100A8/S100A9 complex as
      confirmed by in vitro binding and competition assay, and the treatment of CD69
      with peptide-N-glycosidase significantly abolishes such association. In
      agreement, the glycomics analysis determines the glycosylation site and the N
      glycan composition of CD69, and terminal removal of sialic acid from that N
      linked glycans reverses the generation of forkhead box P3-positive Treg cells
      (23.21%; P < 0.05). More specifically, we showed that CD69-S100A8/S100A9
      association is required for the up-regulation of suppressor of cytokine signaling
      3 resulting in inhibited signaling of signal transducer and activator of
      transcription 3 (36.54% increase upon CD69 silencing; P < 0.01). This might in
      turn support the secretion of key regulator TGF-beta (~ 3.28-fold decrease upon
      CD69 silencing; P < 0.05), leading to reduced production of IL-4 in hPBMCs. Our
      results demonstrate the functional and mechanistic interplays between CD69 and
      S100A8/S100A9 in supporting Treg-cell differentiation.

PMID- 26296370
TI  - Activation of TLR3/interferon signaling pathway by bluetongue virus results in
      HIV inhibition in macrophages.
AB  - Bluetongue virus (BTV), a nonenveloped double-stranded RNA virus, is a potent
      inducer of type Iota interferons in multiple cell systems. In this study, we
      report that BTV16 treatment of primary human macrophages induced both type I and
      III IFN expression, resulting in the production of multiple antiviral factors,
      including myxovirus resistance protein A, 2',5'-oligoadenylate synthetase, and
      the IFN-stimulated gene 56. Additionally, BTV-treated macrophages expressed
      increased HIV restriction factors (apolipoprotein B mRNA-editing enzyme catalytic
      polypeptide 3 G/F/H) and CC chemokines (macrophage inflammatory protein 1-alpha,
      macrophage inflammatory protein 1-beta, regulated on activation of normal T cell
      expressed and secreted), the ligands for HIV entry coreceptor CC chemokine
      receptor type 5. BTV16 also induced the expression of tetherin, which restricts
      HIV release from infected cells. Furthermore, TLR3 signaling of macrophages by
      BTV16 resulted in the induction of several anti-HIV microRNAs (miRNA-28, -29a, 
      125b, -150, -223, and -382). More importantly, the induction of antiviral
      responses by BTV resulted in significant suppression of HIV in macrophages. These
      findings demonstrate the potential of BTV-mediated TLR3 activation in macrophage
      innate immunity against HIV.

PMID- 26296371
TI  - The correlation between the electrode configuration and histopathology of
      irreversible electroporation ablations in prostate cancer patients.
AB  - PURPOSE: Irreversible electroporation (IRE) is a novel minimally invasive therapy
      for prostate cancer using short electric pulses to ablate prostate tissue. The
      purpose of this study is to determine the IRE effects in prostate tissue and
      correlate electrode configuration with the histology of radical prostatectomy
      (RP) specimens. We hypothesize that the area within the electrode configuration
      is completely ablated and that the area within the electrode configuration is
      predictive for the ablated area after treatment. METHODS: A prospective phase
      I/II study was conducted in 16 consecutive patients with histopathologically
      confirmed prostate cancer scheduled for RP. Focal or extended IRE treatment of
      the prostate was performed 4 weeks prior to RP. The locations of the electrodes
      were used to calculate the planned ablation zone. Following RP, the specimens
      were processed into whole-mount sections, histopathology (PA) was assessed and
      ablation zones were delineated. The area of the tissue alteration was determined
      by measuring the surface. The planned and the histological ablation zones were
      compared, analysed per individual patient and per protocol (focal vs. extended).
      RESULTS: All cells within the electrode configuration were completely ablated and
      consisted only of necrotic and fibrotic tissue without leaving any viable cells.
      The histological ablation zone was always larger than the electrodes
      configuration (2.9 times larger for the 3 electrodes configuration and 2.5 times
      larger for the >=4 electrode configuration). These ablation effects extended
      beyond the prostatic capsule in the neurovascular bundle in 13 out of 15 cases.
      CONCLUSIONS: IRE in prostate cancer results in completely ablated, sharply
      demarcated lesions with a histological ablation zone beyond the electrode
      configuration. No skip lesions were observed within the electrode configuration.
      CLINICAL TRIALS: ClinicalTrials.gov Identifier: NCT01790451
      https://clinicaltrials.gov/ct2/show/NCT01790451.

PMID- 26296372
TI  - The PTH-Vitamin D-FGF23 axis.
AB  - Fibroblast growth factor 23 (FGF23) has emerged as an important regulator of
      phosphate and vitamin D homeostasis. It is important to understand how FGF23
      interacts with vitamin D and parathyroid hormone (PTH) in a FGF23-Vitamin D-PTH
      axis to regulate mineral homeostasis. In this review, we discuss the genomic
      structure, and transcriptional, translational, and posttranslational regulation
      of FGF23. We describe its interaction with PTH and vitamin D, disorders of
      altered FGF23 states, and emerging therapies for diseases of FGF23 based upon
      these findings. This discussion helps redefine the role of PTH and vitamin D in
      relation to a complex bone-kidney-parathyroid loop, and points to areas within
      this complicated field in need of further clarification and research. 

PMID- 26296374
TI  - [Total artificial heart].
AB  - BACKGROUND: To date the CardioWestTM total artificial heart is the only
      clinically available implantable biventricular mechanical replacement for
      irreversible cardiac failure. OBJECTIVES: This article presents the indications,
      contraindications, implantation procedere and postoperative treatment. MATERIAL
      AND METHODS: In addition to a overview of the applications of the total
      artificial heart this article gives a brief presentation of the two patients
      treated in our department with the CardioWestTM. RESULTS: The clinical course,
      postoperative rehabilitation, device-related complications and control mechanisms
      are presented. CONCLUSION: The total artificial heart is a reliable implant for
      treating critically ill patients with irreversible cardiogenic shock. A bridge to
      transplantation is feasible with excellent results.

PMID- 26296375
TI  - Efficacy and safety of topical difluprednate in persistent diabetic macular
      edema.
AB  - To evaluate the efficacy and safety of treatment of diabetic macular edema
      (persistent type) with difluprednate ophthalmic emulsion 0.05 % (off label use).
      20 patients with persistent diabetic macular edema were enrolled. In all
      subjects, more than 4 months had passed since prior treatment. All patients were
      treated with difluprednate ophthalmic emulsion 0.05 % three times daily for 3
      months. At the end of 3 months the visual acuity had increased by two lines to a
      mean value of 0.61 +/- 0.18 on logMAR from a baseline value of 0.885 +/- 0.20 and
      the central retinal thickness had decreased from 423 +/- 72.04 microns to 345 +/-
      68.7 microns. Hence, there was a total of 18.4 % decrease in retinal thickness on
      difluprednate. Major side effects included raised intraocular pressure in 20 %.
      Difluprednate is a potent and strong steroid which causes a rapid decrease in
      persistent diabetic macular edema. However, the potential side effect of raised
      intraocular pressure limits its use as an adjuvant therapy in non-steroid
      responders. 

PMID- 26296376
TI  - Examining phylogenetic relationships of Erwinia and Pantoea species using whole
      genome sequence data.
AB  - The genera Erwinia and Pantoea contain species that are devastating plant
      pathogens, non-pathogen epiphytes, and opportunistic human pathogens. However,
      some controversies persist in the taxonomic classification of these two closely
      related genera. The phylogenomic analysis of these two genera was investigated
      via a comprehensive analysis of 25 Erwinia genomes and 23 Pantoea genomes. Single
      copy orthologs could be extracted from the Erwinia/Pantoea core-genome to
      reconstruct the Erwinia/Pantoea phylogeny. This tree has strong bootstrap support
      for almost all branches. We also estimated the in silico DNA-DNA hybridization
      (isDDH) and the average nucleotide identity (ANI) values between each genome;
      strains from the same species showed ANI values >=96% and isDDH values >70%.
      These data confirm that whole genome sequence data provides a powerful tool to
      resolve the complex taxonomic questions of Erwinia/Pantoea, e.g. Pantoea
      agglomerans 299R was not clustered into a single group with other P. agglomerans
      strains, and the ANI values and isDDH values between them were <91% and around
      43.8%, respectively. These data indicate P. agglomerans 299R should not be
      classified into the P. agglomerans species. In addition, another strain (Pantoea
      sp. At_9b) was identified that may represent a novel Pantoea species. We also
      evaluated the performance of six commonly used housekeeping genes (atpD, carA,
      gyrB, infB, recA, and rpoB) in phylogenetic inference. A single gene was not
      enough to obtain a reliable species tree, and it was necessary to use the
      multilocus sequence analysis of the six marker genes to recover the
      Erwinia/Pantoea phylogeny.

PMID- 26296373
TI  - Adverse effects of 5alpha-reductase inhibitors: What do we know, don't know, and
      need to know?
AB  - Steroids are important physiological orchestrators of endocrine as well as
      peripheral and central nervous system functions. One of the key processes for
      regulation of these molecules lies in their enzymatic processing by a family of
      5alpha-reductase (5alpha-Rs) isozymes. By catalyzing a key rate-limiting step in
      steroidogenesis, this family of enzymes exerts a crucial role not only in the
      physiological control but also in pathological events. Indeed, both 5alpha-R
      inhibition and supplementation of 5alpha-reduced metabolites are currently used
      or have been proposed as therapeutic strategies for a wide array of pathological
      conditions. In particular, the potent 5alpha-R inhibitors finasteride and
      dutasteride are used in the treatments of benign prostatic hyperplasia (BPH), as
      well as in male pattern hair loss (MPHL) known as androgenetic alopecia (AGA).
      Recent preclinical and clinical findings indicate that 5alpha-R inhibitors evoke
      not only beneficial, but also adverse effects. Future studies should investigate
      the biochemical and physiological mechanisms that underlie the persistence of the
      adverse sexual side effects to determine why a subset of patients is afflicted
      with such persistence or irreversible adverse effects. Also a better focus of
      clinical research is urgently needed to better define those subjects who are
      likely to be adversely affected by such agents. Furthermore, research on the non
      sexual adverse effects such as diabetes, psychosis, depression, and cognitive
      function are needed to better understand the broad spectrum of the effects these
      drugs may elicit during their use in treatment of AGA or BPH. In this review, we
      will summarize the state of art on this topic, overview the key unresolved
      questions that have emerged on the pharmacological targeting of these enzymes and
      their products, and highlight the need for further studies to ascertain the
      severity and duration of the adverse effects of 5alpha-R inhibitors, as well as
      their biological underpinnings. 

PMID- 26296377
TI  - Comparative analysis of oligonucleotide primers for high-throughput screening of
      genes encoding adenylation domains of nonribosomal peptide synthetases in
      actinomycetes.
AB  - In the biosynthesis of diverse natural bioactive products the adenylation domains
      (ADs) of nonribosomal peptide synthetases select specific precursors from the
      cellular pool and activate them for further incorporation into the scaffold of
      the final compound. Therefore, the drug discovery programs employing PCR-based
      screening studies of microbial collections or metagenomic libraries often use AD
      coding genes as markers of relevant biosynthetic gene clusters. However, due to
      significant sequence diversity of ADs, the conventional approach using only one
      primer pair in a single screening experiment could be insufficient for maximal
      coverage of AD abundance. In this study, the widely used primer pair A3F/A7R was
      compared with the newly designed aa194F/aa413R one by 454 pyrosequencing of two
      sets of actinomycete strains from highly dissimilar environments: subseafloor
      sediments and forest soil. Individually, none of the primer pairs was able to
      cover the overall diversity of ADs. However, due to slightly shifted specificity
      of the primer pairs, the total number and diversity of identified ADs were
      noticeably extended when both primer pairs were used in a single assay.
      Additionally, the efficiency of AD detection by different primer combinations was
      confirmed on the model of Salinispora tropica genomic DNA of known sequence. 

PMID- 26296378
TI  - Molecular characterization of microbial communities in the rhizosphere soils and
      roots of diseased and healthy Panax notoginseng.
AB  - Rhizosphere and root-associated microbial communities are known to be related to
      soil-borne disease and plant health. In the present study, the microbial
      communities in rhizosphere soils and roots of both healthy and diseased Panax
      notoginseng were analyzed by high-throughput sequencing of 16S rRNA for bacteria
      and 18S rRNA internal transcribed spacer for fungi, to reveal the relationship of
      microbial community structure with plant health status. In total, 5593 bacterial
      operational taxonomic units (OTUs) and 963 fungal OTUs were identified in
      rhizosphere soils, while 1794 bacterial and 314 fungal OTUs were identified from
      root samples respectively. Principal coordinate analysis separated the microbial
      communities both in the rhizosphere soils and roots of diseased P. notoginseng
      from healthy plants. Compared to those of healthy P. notoginseng, microbial
      communities in rhizosphere soils and roots of diseased plants showed a decrease
      in alpha diversity. By contrast, bacterial community dissimilarity increased and
      fungal community dissimilarity decreased in rhizosphere soils of diseased plants,
      while both bacterial and fungal community dissimilarity in roots showed no
      significant difference between healthy and diseased plants. Redundancy analysis
      at the phylum level showed that mycorrhizal colonization and soil texture
      significantly affected microbial community composition in rhizosphere soils,
      whereas shoot nutrition status had a significant effect on microbial community
      composition in root samples. Our study provided strong evidence for the
      hypothesis that microbial diversity could potentially serve as an indicator for
      disease outbreak of medicinal plants, and supported the ecological significance
      of microbial communities in maintaining plant healthy and soil fertility. 

PMID- 26296379
TI  - Opposite effects of dihydrotestosterone and estradiol on apoptosis in the
      anterior pituitary gland from male rats.
AB  - Hormones locally synthesized in the anterior pituitary gland are involved in
      regulation of pituitary cell renewal. In the pituitary, testosterone (T) may
      exert its actions per se or by conversion to dihydrotestosterone (DHT) or 17beta
      estradiol (E2) by 5alpha-reductase and aromatase activity, which are expressed in
      this gland. Previous reports from our laboratory showed that estrogens modulate
      apoptosis of lactotropes and somatotropes from female rats. Now, we examined the
      in vitro and in vivo effects of gonadal steroids on apoptosis of anterior
      pituitary cells from adult male rats. T in vitro did not modify apoptosis in
      anterior pituitary cells from gonadectomized (GNX) male rats. DHT, a non
      aromatizable androgen, exerted direct antiapoptotic action on total anterior
      pituitary cells and folliculo-stellate cells, but not on lactotropes,
      somatotropes, or gonadotropes. On the contrary, E2 exerted a rapid apoptotic
      effect on total cells as well as on lactotropes and somatotropes. Incubation of
      anterior pituitary cells with T in presence of Finasteride, an inhibitor of
      5alpha-reductase, increased the percentage of TUNEL-positive cells. In vivo
      administration of DHT to GNX rats reduced apoptosis in the anterior pituitary
      whereas E2 exerted proapoptotic action and reduced cells in G2/M-phase of the
      cell cycle. In summary, our results indicate that DHT and E2 have opposite
      effects on apoptosis in the anterior pituitary gland suggesting that local
      metabolization of T to these steroids could be involved in pituitary cell
      turnover in males. Changes in expression and/or activity of 5alpha-reductase and
      aromatase may play a role in the development of anterior pituitary tumors. 

PMID- 26296380
TI  - A combination of immunohistochemistry and molecular approaches improves highly
      sensitive detection of BRAF mutations in papillary thyroid cancer.
AB  - The optimal method for BRAF mutation detection remains to be determined despite
      advances in molecular detection techniques. The aim of this study was to compare,
      against classical Sanger sequencing, the diagnostic performance of two of the
      most recently developed, highly sensitive methods: BRAF V600E
      immunohistochemistry (IHC) and peptide nucleic-acid (PNA)-clamp qPCR. BRAF exon
      15 mutations were searched in formalin-fixed paraffin-embedded tissues from 86
      papillary thyroid carcinoma using the three methods. The limits of detection of
      Sanger sequencing in borderline or discordant cases were quantified by next
      generation sequencing. BRAF mutations were found in 74.4 % of cases by PNA, in 71
      % of cases by IHC, and in 64 % of cases by Sanger sequencing. Complete
      concordance for the three methods was observed in 80 % of samples. Better
      concordance was observed with the combination of two methods, particularly PNA
      and IHC (59/64) (92 %), while the combination of PNA and Sanger was concordant in
      55 cases (86 %). Sensitivity of the three methods was 99 % for PNA, 94.2 % for
      IHC, and 89.5 % for Sanger. Our data show that IHC could be used as a cost
      effective, first-line method for BRAF V600E detection in daily practice, followed
      by PNA analysis in negative or uninterpretable cases, as the most efficient
      method. PNA-clamp quantitative PCR is highly sensitive and complementary to IHC
      as it also recognizes other mutations besides V600E and it is suitable for
      diagnostic purposes. 

PMID- 26296381
TI  - Symptom severity of bipolar disorder during the menopausal transition.
AB  - BACKGROUND: Little is known about the mood symptom experience of women with
      bipolar disorder during the menopausal transition (MT). Yet times of rapid
      hormonal decline, such as the postpartum, are associated with increased risk of
      severe mood episodes in bipolar disorder, and the MT is a time of increased risk
      for unipolar depression in women with or without a history of depression.
      METHODS: Enrollment included 56 women 40-60 years old diagnosed in the bipolar
      spectrum who were experiencing menopausal symptoms or were up to 5 years since
      their final menstrual period. Menopausal stages included early menopause, late
      menopause, or early postmenopause based on standardized criteria. Observational,
      prospective standardized mood symptom and reproductive hormone assessments were
      completed periodically. Concurrent menopausal symptoms as well as history of mood
      exacerbation during past reproductive events were assessed. RESULTS: Forty-four
      women were included in the main analysis. The average Montgomery-Asberg
      Depression Rating Scale (MADRS) score was 4.43 points higher in the late
      transition/early postmenopausal stage women (n = 29) compared to the early
      menopausal stage women (n = 15) (+/-SE 2.14; p = 0.039), corresponding to a
      roughly 10 % higher score (range 0-40) in the late/post stage across all study
      visits. Results were similar for the Young Mania Rating Scale (YMRS), where the
      average score was 2.54 points higher in the late/early postmenopausal stage women
      compared to the early menopausal stage women (+/-SE 1.15; p = 0.027), also
      roughly 10 % higher (range 0-26). Estradiol and follicle-stimulating hormone
      (FSH) absolute levels as well as between-visit change in levels were not notably
      associated with YMRS or MADRS during study observation. Total Greene Climacteric
      Symptom (menopausal symptom) score was significantly associated with MADRS but
      not YMRS. History of mood exacerbation premenstrually and/or postpartum was not
      significantly associated with YMRS or MADRS severity during the MT. CONCLUSIONS:
      These results support the theory that times of increased reproductive hormonal
      changes, such as the late MT and early postmenopause, here compared to early MT,
      are associated with greater mood symptom severity in bipolar spectrum women.
      Nonetheless, absolute or change in FSH and estradiol levels were not
      significantly associated with depression or mood elevation severity.

PMID- 26296382
TI  - Comparative whole genome transcriptome and metabolome analyses of five Klebsiella
      pneumonia strains.
AB  - The integration of transcriptomics and metabolomics can provide precise
      information on gene-to-metabolite networks for identifying the function of novel
      genes. The goal of this study was to identify novel gene functions involved in
      2,3-butanediol (2,3-BDO) biosynthesis by a comprehensive analysis of the
      transcriptome and metabolome of five mutated Klebsiella pneumonia strains (?wabG
      = SGSB100, ?wabG?budA = SGSB106, ?wabG?budB = SGSB107, ?wabG?budC = SGSB108,
      ?wabG?budABC = SGSB109). First, the transcriptomes of all five mutants were
      analyzed and the genes exhibiting reproducible changes in expression were
      determined. The transcriptome was well conserved among the five strains, and
      differences in gene expression occurred mainly in genes coding for 2,3-BDO
      biosynthesis (budA, budB, and budC) and the genes involved in the degradation of
      reactive oxygen, biosynthesis and transport of arginine, cysteine biosynthesis,
      sulfur metabolism, oxidoreductase reaction, and formate dehydrogenase reaction.
      Second, differences in the metabolome (estimated by carbon distribution, CO2
      emission, and redox balance) among the five mutant strains due to gene alteration
      of the 2,3-BDO operon were detected. The functional genomics approach integrating
      metabolomics and transcriptomics in K. Pneumonia presented here provides an
      innovative means of identifying novel gene functions involved in 2,3-BDO
      biosynthesis metabolism and whole cell metabolism. 

PMID- 26296384
TI  - Re: Flexible ureteroscopic laser lithotripsy for upper urinary tract stone
      disease in patients with spinal cord injury.

PMID- 26296383
TI  - Knowledge, attitudes, and practice patterns of recurrent urinary stones
      prevention in Saudi Arabia.
AB  - The purpose of this study is to assess the knowledge, attitudes, and practice
      patterns of urologists in Saudi Arabia regarding prevention of recurrent stone
      formation and how much they follow preventive stone disease management
      guidelines. A questionnaire about knowledge, attitudes, and practice patterns of
      urologists in Saudi Arabia regarding prevention of recurrent stone formation was
      used. The survey comprised three domains: knowledge, attitudes, and practice
      patterns. Data about gender, duration of experience and health care sector were
      also collected. Individual responses were recorded, tabulated and compared using
      descriptive statistics. The overall response rate was 38.8%. All respondents were
      male urologists. Most of them (62, 71.3%) had an experience of 5-20 years in
      management of stone disease patients and the majority (74, 85.1%) belonged to the
      governmental health care sector. A total of 51% of the respondents answered in
      concordance with the best practice guidelines in at least half of the questions
      and 40% in all of the questions. Overall, practice patterns of 58% of the
      respondents were in concordance with the best practice guidelines in all the
      questions except for the question of practices regarding stone analysis. As
      regards to attitude domain, a total of 58.7% respondents expressed their
      agreement or strong agreement with the questions. Urologists' knowledge of stone
      recurrence preventive programs is suboptimal. They do not apply effectively the
      best stone prevention practice guidelines in their daily practice as well.
      Efforts to increase knowledge and enforce its application in daily practice are
      strongly warranted.

PMID- 26296385
TI  - Acute ST-segment elevation myocardial infarction as the first manifestation of
      essential thrombocytosis successfully treated with thrombectomy alone.
AB  - A patient with no conventional cardiovascular risk factors presented with
      inferior ST-elevation myocardial infarction which was finally diagnosed as a case
      of essential thrombocytosis. This case demonstrated that thrombectomy alone was
      sufficient for the treatment of his coronary occlusion. Furthermore, this case
      report highlights the importance of evaluating rare causes of myocardial
      infarction other than atherosclerosis and that internists and cardiologists
      should be aware of essential thrombocytosis as a known cause of myocardial
      infarction, particularly in patients with no underlying cardiovascular risk
      factors. 

PMID- 26296386
TI  - RHOA mutation may be associated with diffuse-type gastric cancer progression, but
      is it gain or loss?

PMID- 26296387
TI  - Generation and characterization of a breast carcinoma model by PyMT
      overexpression in mammary epithelial cells of tree shrew, an animal close to
      primates in evolution.
AB  - The tree shrew is becoming an attractive experimental animal model for human
      breast cancer owing to a closer relationship to primates/humans than rodents.
      Tree shrews are superior to classical primates because tree shrew are easier to
      manipulate, maintain and propagate. It is required to establish a high-efficiency
      tree shrew breast cancer model for etiological research and drug assessment. Our
      previous studies suggest that 7,12-dimethylbenz(a)anthracene (DMBA) and
      medroxyprogesterone acetate (MPA) induce breast tumors in tree shrews with a low
      frequency (<50%) and long latency (~ 7-month), making these methods less than
      ideal. We induced mammary tumors in tree shrew (Tupaia belangeri chinensis) by
      injection of lentivirus expressing the PyMT oncogene into mammary ducts of 22
      animals. Most tree shrews developed mammary tumors with a latency of about three
      weeks, and by 7 weeks all injected tree shrews had developed mammary tumors.
      Among these, papillary carcinoma is the predominant tumor type. One case showed
      lymph node and lung metastasis. Interestingly, the expression levels of
      phosphorylated AKT, ERK and STAT3 were elevated in 41-68% of PyMT-induced mammary
      tumors, but not all tumors. Finally, we observed that the growth of PyMT-induced
      tree shrew mammary tumors was significantly inhibited by Cisplatin and
      Epidoxorubicin. PyMT-induced tree shrew mammary tumor model may be suitable for
      further breast cancer research and drug development, due to its high efficiency
      and short latency.

PMID- 26296388
TI  - Induction of Secondary Structure through Micellization of an Oppositely Charged
      Pair of Homochiral Block- and Homopolypeptides in an Aqueous Medium.
AB  - Polyion complex (PIC) formation is an attractive method for obtaining molecular
      assemblies owing to their facile fabrication process in aqueous media, but more
      insights are required in order to control the higher-dimensional structures of
      polypeptide-based PICs. Herein, the PIC formation behavior of oppositely charged
      homochiral polypeptides, poly-L-lysine and poly(ethylene glycol)-b-poly(L
      glutamate) (PEG-PLG), and their secondary structures are carefully studied in
      water. PIC formation takes place in a polymer concentration-dependent manner, and
      clear beta-sheet formation is observed at polymer concentrations >=0.3 mg mL(-1).
      The results also confirm that multimolecular aggregation is a prerequisite for
      beta-sheet formation, which indicates that the inner hydrophobic environment of
      PICs is favorable for beta-sheet formation. Furthermore, the PEG weight fraction,
      stereoregularity of the polypeptide, and ionic strength of the solutions are
      found to be key factors for generating a secondary structure, presumably because
      these factors can contribute to the tuning of the inner environment of PICs. This
      method of producing water-soluble nanoassemblies from oppositely charged
      polypeptides may expedite self-assembly studies in biological systems and be
      incorporated into various molecular systems to exploit protein-mimicking
      features.

PMID- 26296389
TI  - Cystic adventitial disease in the popliteal artery with a joint connection to the
      superior tibiofibular joint: Radiological evidence to support the unifying
      articular theory.

PMID- 26296390
TI  - Effect of flavonoids on remineralization of artificial root caries.
AB  - BACKGROUND: This study compared the effects of three flavonoids, including
      proanthocyanidin, naringin and quercetin on remineralization of artificial root
      caries. METHODS: Demineralized root fragments (n = 75) were randomly divided into
      five groups for treatment with the remineralizing agents for 10 minutes: (1) 6.5%
      proanthocyanidin; (2) 6.5% naringin; (3) 6.5% quercetin; (4) 1000 ppm fluoride;
      and (5) deionized water (control). The demineralized samples were pH-cycled
      through treatment solutions, acidic buffer and neutral buffer for eight days at
      six cycles per day. The remineralization effects were evaluated using Knoop
      microhardness, transverse microradiography (lesion depth and mineral loss) and
      confocal laser scanning microscopy. Microhardness at different lesion depths was
      analysed with two-way ANOVA and Tukey's test, while lesion depths and mineral
      loss were analysed with one-way ANOVA and Tukey's test. RESULTS: Artificial
      caries lesions treated with fluoride and flavonoids showed significantly greater
      hardness than the control group (p < 0.05). Both lesion depths and mineral loss
      of the flavonoid treated groups were significantly lower than the control group
      (p < 0.05), but significantly higher than the fluoride treated group. No
      significant difference in lesion depth and mineral loss was found among the three
      flavonoids (p > 0.05). CONCLUSIONS: All three flavonoids showed positive effects
      on artificial root caries remineralization, which are significantly lower than
      that of 1000 ppm fluoride.

PMID- 26296391
TI  - Everolimus overexposure in a heart transplant patient receiving clarithromycin
      for the treatment of pneumonia.

PMID- 26296392
TI  - Dissemination of an Electronic Manual to Build Capacity for Implementing Farmers'
      Markets with Community Health Centers.
AB  - Community-university partnerships can lend themselves to the development of tools
      that encourage and promote future community health development. The electronic
      manual, "Building Farmacies," describes an approach for developing capacity and
      sustaining a community health center-based farmers' market that emerged through a
      community-university partnership. Manual development was guided by the Knowledge
      to Action Framework and experiences developing a multivendor, produce-only
      farmers' market at a community health center in rural South Carolina. The manual
      was created to illustrate an innovative solution for community health
      development. The manual was disseminated electronically through 25 listservs and
      interested individuals voluntarily completed a Web-based survey to access the
      free manual. During the 6-month dissemination period, 271 individuals downloaded
      the manual. Findings highlighted the value of translating community-based
      participatory research into user-friendly manuals to guide future intervention
      development and dissemination approaches, and demonstrate the need to include
      capacity building opportunities to support translation and adoption of
      interventions. 

PMID- 26296393
TI  - Detection of the F129L mutation in the cytochrome b gene in Phakopsora
      pachyrhizi.
AB  - BACKGROUND: Asian soybean rust, caused by Phakopsora pachyrhizi, is mostly
      controlled by demethylation inhibitor (DMI) and quinone outside inhibitor (QoI)
      fungicides. Mutations in the cytochrome b (CYTB) gene can lead to pathogen
      resistance to QoIs. The occurrence of the mutations in codons 129, 137 and 143 in
      the CYTB gene was investigated, and a pyrosequencing assay was developed for
      rapid and quantitative detection of the F129L mutation. RESULTS: Molecular
      analysis of the CYTB gene showed the presence of the F129L mutation in field
      samples and monouredinial isolates, while other mutations (G143A and G137R) were
      not found. The pyrosequencing was an effective method for quantitative detection
      of the F129L mutation, and many of the P. pachyrhizi samples showed high
      frequency of F129L. CONCLUSION: This is the first report of the occurrence of the
      F129L mutation in P. pachyrhizi. The practical relevance of this mutation for
      field efficacy of QoIs needs further investigation. (c) 2015 Society of Chemical
      Industry.

PMID- 26296394
TI  - A randomized trial of diagnostic ultrasound to improve outcomes in focal
      neuropathies.
AB  - INTRODUCTION: Neuromuscular ultrasound is valid, reliable, and accurate, but it
      is not known whether combining it with electrodiagnostic studies leads to better
      outcomes in individuals with focal neuropathies. METHODS: One hundred twenty
      individuals with focal neuropathy, based on history, examination, and
      electrodiagnosis, were enrolled in this study. All patients underwent
      neuromuscular ultrasound and were randomized to either have their ultrasound
      results sent to the referring physician or not have them sent. Outcomes were
      assessed at 6 months by evaluators blinded to group assignment. RESULTS: The
      Overall Disability Sum Score and 7 of 8 domains of the Medical Outcomes Study 36
      item Short-Form Health Survey (SF-36) showed more improvement in the "report
      sent" group, although only the general health perception domain was significant
      (P = 0.005). CONCLUSIONS: Most 6-month outcomes did not reach statistical
      significance between the 2 groups. However, the "report sent" group had trends
      toward better outcomes, with significance being reached in the general health
      perception domain of the SF-36.

PMID- 26296395
TI  - Horizontal slices of mouse retina expose horizontal cells and their properties
      (Commentary on Feigenspan & Babai).

PMID- 26296397
TI  - International medical graduates: acculturation, repatriation and the third
      culture kids of medicine.

PMID- 26296398
TI  - Collaborative relationships and learning in rural communities.

PMID- 26296399
TI  - In my mind: how situation awareness can facilitate expert performance and foster
      learning.

PMID- 26296400
TI  - Mindless evaluations by students and teachers.

PMID- 26296401
TI  - When I say ... micro learning environment.

PMID- 26296402
TI  - When I say ... reciprocal illumination.

PMID- 26296403
TI  - Educational interventions for international medical graduates: a review and
      agenda.
AB  - CONTEXT: International medical graduates (IMGs) play key roles in the health
      systems of their host countries, but face unique challenges, which makes the
      provision of effective, tailored support for IMGs essential. OBJECTIVES: Research
      on the effectiveness of educational interventions for IMGs was reviewed to
      characterise current knowledge and guide future research and education. METHODS:
      PubMed, Web of Science and EMBASE were searched for relevant articles published
      to October 2014, describing a systematic evaluation of educational interventions
      designed for IMGs that included at least one post-intervention outcome. Articles
      were coded independently by two or more researchers for content and methodology,
      and discussed to reach consensus. RESULTS: Twenty-two articles were identified,
      describing a wide variety of interventions, content and durations of
      intervention. Clinical topics and general principles of cross-cultural competency
      were the most common content areas included in curricula (13 and 12 articles,
      respectively). All studies deemed the interventions evaluated to be successful.
      However, only one study drew from theory on cross-cultural differences to guide
      either the curriculum or evaluation. Additionally, study designs were generally
      weak; no studies featured random assignment to treatment versus control groups,
      most studies did not use control groups at all, and no studies compared the
      effectiveness of different interventions. CONCLUSIONS: Research into education
      for IMGs is critically important but currently underdeveloped. An abundance of
      justification studies and lack of clarification studies parallel other areas of
      medical education. Academic fields outside medical education, such as those of
      cross-cultural psychology and expatriate management, are highly relevant;
      researchers from these areas should be sought for collaboration. Future research
      should employ conceptual frameworks in order to facilitate a broader, more
      nuanced consideration of the diversity of individual IMGs, educational and
      medical contexts, interventions and outcomes. Rigorous comparative effectiveness
      research is lacking, but represents a promising avenue for future scholarship.

PMID- 26296404
TI  - Interprofessional education: does recent literature from rural settings offer
      insights into what really matters?
AB  - CONTEXT: As rural health staff of different disciplines often know one another
      and share workplace facilities, rural areas are well suited to the implementation
      of interprofessional education (IPE) strategies. Details of such strategies are
      often shared in journal articles so that educators can learn from and build on
      the experiences of others. A common theme in the apparent success of rural
      interprofessional initiatives concerns collaborative relationships among
      educators. However, do readers of journals see the full picture of the
      collaborative relationships among educators of different disciplines as they plan
      and implement strategies? METHODS: A literature interpretation informed by
      philosophical hermeneutics was used to explore the nature of educators'
      collaborative relationships in the planning and implementation of IPE initiatives
      as portrayed by authors of articles on rural IPE. Twenty-four articles suitable
      for inclusion in the text set were identified through searches of databases and
      relevant journals. RESULTS: The nature of the collaborative relationships
      involved in planning and implementing educational strategies was rarely explicit.
      However, within an implied sense of interpersonal relationships, three themes
      were interpreted: grounded beginnings; untold stories, and anthropomorphised
      collectives. CONCLUSIONS: Being explicit about educators' collaborative
      relationships may have potential to improve the transferability of IPE strategies
      to other contexts. A flowchart is presented to encourage authors to: (i) consider
      how to portray educators' collaborative relationships, and (ii) reflect on how
      these collaborative relationships may impact on the success, or otherwise, of
      their IPE projects.

PMID- 26296405
TI  - Mental imagery and learning: a qualitative study in orthopaedic trauma surgery.
AB  - CONTEXT: Good preparation for surgical procedures has been linked to better
      performance and enhanced learning in the operating theatre. Mental imagery is
      increasingly used to enhance performance in competitive sport and there has been
      recent interest in applying this in surgery. OBJECTIVES: This study aims to
      identify the mental imagery components of preoperative preparation in orthopaedic
      trauma surgery and to locate these practices in existing socio-material theory in
      order to produce a model useful for surgical skills training. METHODS: Semi
      structured interviews were conducted with nine orthopaedic surgeons. Participants
      were identified by personal recommendation as regularly performing complex trauma
      operations to a high standard, and by affiliation to an international instruction
      course in trauma surgery. Interviews were audio-recorded and transcripts were
      independently analysed using thematic analysis. RESULTS: Analysis revealed that
      surgeons interact intensively with multiple colleagues and materials during their
      preparatory activities. Such interactions stimulate mental imagery in order to
      build strategy and rehearse procedures, which, in turn, stimulate preparatory
      interactions. Participants identified the discussion of a preoperative 'plan' as
      a key engagement tool for training junior surgeons and as a form of currency by
      which a trainee may increase his or her participation in a procedure.
      CONCLUSIONS: Preoperative preparation can be thought of as a socio-material
      ontology requiring a surgeon to negotiate imaginal, verbal and physical
      interactions with people, materials and his or her own mental imagery. Actor
      network theory is useful for making sense of these interactions and for allowing
      surgeons to interrogate their own preparative processes. We recommend supervisors
      to use a form of preoperative plan as a teaching tool and to encourage trainees
      to develop their own preparatory skills. The ability of a trainee to demonstrate
      sound preparation is an indicator of readiness to perform a procedure.

PMID- 26296406
TI  - Considerations in the use of reflective writing for student assessment: issues of
      reliability and validity.
AB  - CONTEXT: Reflective writing is a popular tool to support the growth of reflective
      capacity in undergraduate medical learners. Its popularity stems from research
      suggesting that reflective capacity may lead to improvements in skills such as
      empathy, communication, collaboration and professionalism. This has led to
      assumptions that reflective writing can also serve as a tool for student
      assessment. However, evidence to support the reliability and validity of
      reflective writing as a meaningful assessment strategy is lacking. METHODS: Using
      a published instrument for measuring 'reflective capacity' (the Reflection
      Evaluation for Learners' Enhanced Competencies Tool [REFLECT]), four trained
      raters independently scored four samples of writing from each of 107
      undergraduate medical students to determine the reliability of reflective writing
      scores. REFLECT scores were then correlated with scores on a Year 4 objective
      structured clinical examination (OSCE) and Year 2 multiple-choice question (MCQ)
      examinations to examine, respectively, convergent and divergent validity.
      RESULTS: Across four writing samples, four-rater Cronbach's alpha-values ranged
      from 0.72 to 0.82, demonstrating reasonable inter-rater reliability with four
      raters using the REFLECT rubric. However, inter-sample reliability was fairly low
      (four-sample Cronbach's alpha = 0.54, single-sample intraclass correlation
      coefficient: 0.23), which suggests that performance on one reflective writing
      sample was not strongly indicative of performance on the next. Approximately 14
      writing samples are required to achieve reasonable inter-sample reliability. The
      study found weak, non-significant correlations between reflective writing scores
      and both OSCE global scores (r = 0.13) and MCQ examination scores (r = 0.10),
      demonstrating a lack of relationship between reflective writing and these
      measures of performance. CONCLUSIONS: Our findings suggest that to draw
      meaningful conclusions about reflective capacity as a stable construct in
      individuals requires 14 writing samples per student, each assessed by four or
      five raters. This calls into question the feasibility and utility of using
      reflective writing rigorously as an assessment tool in undergraduate medical
      education.

PMID- 26296407
TI  - Relatively speaking: contrast effects influence assessors' scores and narrative
      feedback.
AB  - CONTEXT: In prior research, the scores assessors assign can be biased away from
      the standard of preceding performances (i.e. 'contrast effects' occur).
      OBJECTIVES: This study examines the mechanism and robustness of these findings to
      advance understanding of assessor cognition. We test the influence of the
      immediately preceding performance relative to that of a series of prior
      performances. Further, we examine whether assessors' narrative comments are
      similarly influenced by contrast effects. METHODS: Clinicians (n = 61) were
      randomised to three groups in a blinded, Internet-based experiment. Participants
      viewed identical videos of good, borderline and poor performances by first-year
      doctors in varied orders. They provided scores and written feedback after each
      video. Narrative comments were blindly content-analysed to generate measures of
      valence and content. Variability of narrative comments and scores was compared
      between groups. RESULTS: Comparisons indicated contrast effects after a single
      performance. When a good performance was preceded by a poor performance, ratings
      were higher (mean 5.01, 95% confidence interval [CI] 4.79-5.24) than when
      observation of the good performance was unbiased (mean 4.36, 95% CI 4.14-4.60; p
      < 0.05, d = 1.3). Similarly, borderline performance was rated lower when preceded
      by good performance (mean 2.96, 95% CI 2.56-3.37) than when viewed without
      preceding bias (mean 3.55, 95% CI 3.17-3.92; p < 0.05, d = 0.7). The series of
      ratings participants assigned suggested that the magnitude of contrast effects is
      determined by an averaging of recent experiences. The valence (but not content)
      of narrative comments showed contrast effects similar to those found in numerical
      scores. CONCLUSIONS: These findings are consistent with research from behavioural
      economics and psychology that suggests judgement tends to be relative in nature.
      Observing that the valence of narrative comments is similarly influenced suggests
      these effects represent more than difficulty in translating impressions into a
      number. The extent to which such factors impact upon assessment in practice
      remains to be determined as the influence is likely to depend on context.

PMID- 26296408
TI  - Twenty Questions game performance on medical school entrance predicts clinical
      performance.
AB  - CONTEXT: This study is based on the premise that the game of 'Twenty Questions'
      (TQ) tests the knowledge people acquire through their lives and how well they
      organise and store it so that they can effectively retrieve, combine and use it
      to address new life challenges. Therefore, performance on TQ may predict how
      effectively medical school applicants will organise and store knowledge they
      acquire during medical training to support their work as doctors. OBJECTIVES:
      This study was designed to determine whether TQ game performance on medical
      school entrance predicts performance on a clinical performance examination near
      graduation. METHODS: This prospective, longitudinal, observational study involved
      each medical student in one class playing a game of TQ on a non-medical topic
      during the first week of medical school. Near graduation, these students
      completed a 14-case clinical performance examination. Performance on the TQ task
      was compared with performance on the clinical performance examination. RESULTS:
      The 24 students who exhibited a logical approach to the TQ task performed better
      on all senior clinical performance examination measures than did the 26 students
      who exhibited a random approach. Approach to the task was a better predictor of
      senior examination diagnosis justification performance than was the Medical
      College Admission Test (MCAT) Biological Science Test score and accounts for a
      substantial amount of score variation not attributable to a co-relationship with
      MCAT Biological Science Test performance. CONCLUSIONS: Approach to the TQ task
      appears to be one reasonable indicator of how students process and store
      knowledge acquired in their everyday lives and may be a useful predictor of how
      they will process the knowledge acquired during medical training. The TQ task can
      be fitted into one slot of a mini medical interview.

PMID- 26296409
TI  - A curious case of the phantom professor: mindless teaching evaluations by medical
      students.
AB  - CONTEXT: Student evaluations of teaching (SETs) inform faculty promotion
      decisions and course improvement, a process that is predicated on the assumption
      that students complete the evaluations with diligence. Anecdotal evidence
      suggests that this may not be so. OBJECTIVES: We sought to determine the degree
      to which medical students complete SETs deliberately in a classroom-style, multi
      instructor course. METHODS: We inserted one fictitious lecturer into each of two
      pre-clinical courses. Students were required to submit their anonymous ratings of
      all lecturers, including the fictitious one, within 2 weeks after the course
      using a 5-point Likert scale, but could choose not to evaluate a lecturer. The
      following year, we repeated this but included a portrait of the fictitious
      lecturer. The number of actual lecturers in each course ranged from 23 to 52.
      RESULTS: Response rates were 99% and 94%, respectively, in the 2 years of the
      study. Without a portrait, 66% (183 of 277) of students evaluated the fictitious
      lecturer, but fewer students (49%, 140 of 285) did so with a portrait (chi
      squared test, p < 0.0001). CONCLUSIONS: These findings suggest that many medical
      students complete SETs mindlessly, even when a photograph is included, without
      careful consideration of whom they are evaluating and much less of how that
      faculty member performed. This hampers programme quality improvement and may harm
      the academic advancement of faculty members. We present a framework that suggests
      a fundamentally different approach to SET that involves students prospectively
      and proactively.

PMID- 26296410
TI  - Predicting performance: relative importance of students' background and past
      performance.
AB  - CONTEXT: Despite evidence for the predictive value of both pre-admission
      characteristics and past performance at medical school, their relative
      contribution to predicting medical school performance has not been thoroughly
      investigated. OBJECTIVES: This study was designed to determine the relative
      importance of pre-admission characteristics and past performance in medical
      school in predicting student performance in pre-clinical and clinical training.
      METHODS: This longitudinal prospective study followed six cohorts of students
      admitted to a Dutch, 6-year, undergraduate medical course during 2002-2007 (n =
      2357). Four prediction models were developed using multivariate logistic
      regression analysis. Main outcome measures were 'Year 1 course completion within
      1 year' (models 1a, 1b), 'Pre-clinical course completion within 4 years' (model
      2) and 'Achievement of at least three of five clerkship grades of >= 8.0' (model
      3). Pre-admission characteristics (models 1a, 1b, 2, 3) and past performance at
      medical school (models 1b, 2, 3) were included as predictor variables. RESULTS:
      In model 1a - including pre-admission characteristics only - the strongest
      predictor for Year 1 course completion was pre-university grade point average
      (GPA). Success factors were 'selected by admission testing' and 'age > 21 years';
      risk factors were 'Surinamese/Antillean background', 'foreign pre-university
      degree', 'doctor parent' and male gender. In model 1b, number of attempts and GPA
      at 4 months were the strongest predictors for Year 1 course completion, and male
      gender remained a risk factor. Year 1 GPA was the strongest predictor for pre
      clinical course completion, whereas being male or aged 19-21 years were risk
      factors. Pre-clinical course GPA positively predicted clinical performance,
      whereas being non-Dutch or a first-generation university student were important
      risk factors for lower clinical grades. Nagelkerke's R(2) ranged from 0.16 to
      0.62. CONCLUSIONS: This study not only confirms the importance of past
      performance as a predictor of future performance in pre-clinical training, but
      also reveals the importance of a student's background as a predictor in clinical
      training. These findings have important practical implications for selection and
      support during medical school.

PMID- 26296411
TI  - The multiple spaces for health professional students' learning.

PMID- 26296412
TI  - The endless potential of social media in medical education.

PMID- 26296413
TI  - Heterogenous haemodynamic effects of adaptive servoventilation therapy in
      sleeping patients with heart failure and Cheyne-Stokes respiration compared to
      healthy volunteers.
AB  - This study investigated the haemodynamic effects of adaptive servoventilation
      (ASV) in heart failure (HF) patients with Cheyne-Stokes respiration (CSR) versus
      healthy controls. Twenty-seven HF patients with CSR and 15 volunteers were
      ventilated for 1 h using a new ASV device (PaceWaveTM). Haemodynamics were
      continuously and non-invasively recorded at baseline, during ASV and after
      ventilation. Prior to the actual study, a small validation study was performed to
      validate non-invasive measurement of Stroke volume index (SVI). Non-invasive
      measurement of SVI showed a marginal overall difference of -0.03 +/- 0.41
      L/min/m(2) compared to the current gold standard (Thermodilution-based
      measurement). Stroke volume index (SVI) increased during ASV in HF patients (29.7
      +/- 5 to 30.4 +/- 6 to 28.7 +/- 5 mL/m(2), p < 0.05) and decreased slightly in
      volunteers (50.7 +/- 12 to 48.6 +/- 11 to 47.9 +/- 12 mL/m(2)). Simultaneously, 1
      h of ASV was associated with a trend towards an increase in parasympathetic
      nervous activity (PNA) in HF patients and a trend towards an increase in
      sympathetic nervous activity (SNA) in healthy volunteers. Blood pressure (BP) and
      total peripheral resistance response increased significantly in both groups,
      despite marked inter-individual variation. Effects were independent of vigilance.
      Predictors of increased SVI during ASV in HF patients included preserved right
      ventricular function, normal resting BP, non-ischaemic HF aetiology, mitral
      regurgitation and increased left ventricular filling pressures. This study
      confirms favourable haemodynamic effects of ASV in HF patients with CSR
      presenting with mitral regurgitation and/or increased left ventricular filling
      pressures, but also identified a number of new predictors. This might be mediated
      by a shift towards more parasympathetic nervous activity in those patients. 

PMID- 26296414
TI  - The diversity changes of soil microbial communities stimulated by climate, soil
      type and vegetation type analyzed via a functional gene array.
AB  - The aim of this study was to analyze the changes of soil microbial communities
      stimulated by climate, soil type and vegetation type using a functional gene
      array. The dataset GSE51592 was obtained from Gene Expression Omnibus, including
      54 soil samples. Genetic diversity variation of samples under different sites,
      soil and vegetation types was examined by calculating the percentage of specific
      gene number in each sample. Furthermore, gene functional categories and
      microorganism species in samples under different environmental factors were
      respectively divided. Gene number in samples with cropping was higher than in
      samples without cropping. When site, soil type and vegetation type were as the
      sole variable, respectively, the percentage of specific genes in samples from
      Yingtan, in phaeozem samples and in samples with cropping was higher.
      Furthermore, the percentage of gene number in organic remediation for phaeozem
      and cambisol samples was significant at p < 0.05, comparing with that for acrisol
      samples. At superkingdom level of microorganisms, for the same category, there
      was no significant difference (p < 0.05) between the samples. At phylum level,
      for the categories of Bacteroidetes and Cyanobacteria, the percentage of gene
      number in cambisol samples was significantly higher (p < 0.05). Conversely, in
      the category of Proteobacteria, the percentage of gene number in phaeozem and
      acrisol samples was markedly higher (p < 0.05). Microbial diversity of soil was
      cooperatively driven by climate, soil type and vegetation type. 

PMID- 26296415
TI  - Understanding the role of clay minerals in the chromium(VI) bioremoval by
      Pseudomonas aeruginosa CCTCC AB93066 under growth condition: microscopic,
      spectroscopic and kinetic analysis.
AB  - Laboratory batch experiments were conducted to investigate the role of clay
      minerals, e.g., kaolinite and vermiculite, in microbial Cr(VI) reduction by
      Pseudomonas aeruginosa under growth condition in glucose-amended mediums as a
      method for treating Cr(VI)-contaminated subsurface environment such as soil. Our
      results indicated that glucose could acted as an essential electron donor, and
      clay minerals significantly enhanced microbial Cr(VI) reduction rates by
      improving the consumption rate of glucose and stimulating the growth and
      propagation of P. aeruginosa. Cr(VI) bioreduction by both free cells and clay
      minerals-amended cells followed the pseudo-first-order kinetic model, with the
      latter one fitting better. The mass balance analyses and X-ray photoelectron
      spectroscopy analysis found that Cr(VI) was reduced to Cr(III) and the adsorption
      of total chromium on clay minerals-bacteria complex was small, implying that
      Cr(VI) bioremoval was not mainly due to the adsorption of Cr(VI) onto cells or
      clay minerals or clay minerals-cells complex but mainly due to the Cr(VI)
      reduction capacity of P. aeruginosa under the experimental conditions studied
      (e.g., pH 7). Atomic force microscopy revealed that the addition of clay minerals
      (e.g. vermiculite) decreased the surface roughness of Cr(VI)-laden cells and
      changed the cell morphology and dimension. Fourier transform infrared
      spectroscopy revealed that organic matters such as aliphatic species and/or
      proteins played an important role in the combination of cells and clay minerals.
      Scanning electron microscopy confirmed the attachment of cells on the surface of
      clay minerals, indicating that clay minerals could provide a microenvironment to
      protect cells from Cr(VI) toxicity and serve as growth-supporting materials.
      These findings manifested the underlying influence of clay minerals on microbial
      reduction of Cr(VI) and gave an understanding of the interaction between
      pollutants, the environment and the biota. 

PMID- 26296416
TI  - [Restoration of ulnar collateral ligament stability of the metacarpophalangeal
      joint of the thumb].
AB  - OBJECTIVE: Restoration of ulnar collateral ligament stability of the
      metacarpophalangeal (MP) joint of the thumb with elimination of palmar
      subluxation while retaining mobility for chronic instability without
      osteoarthritis. INDICATIONS: Acquired or congenital chronic instability of the MP
      joint of the thumb with compelling reasons for joint preservation and against
      arthrodesis, e.g., an arthrodesis or arthritis of adjacent joints.
      CONTRAINDICATIONS: Arthritis of the thumb MP joint. Contractures of the MP joint.
      Low natural range of motion of the joint (compared to the contralateral hand).
      Additional palmar instability with significant hyperextensibility. Infections.
      Lesions to the median and/or ulnar nerve with impaired active mobility. SURGICAL
      TECHNIQUE: Anatomical reconstruction of the ulnar collateral ligament and the
      accessory collateral ligament using a tendon graft (palmaris longus tendon).
      Ulnar approach, transosseous course of the tendon graft and elimination of
      subluxation. POSTOPERATIVE MANAGEMENT: Splint for 5 weeks and hand therapy.
      RESULTS: Of 12 patients undergoing this type of ligament reconstruction, all
      achieved good stability and pain-free range of motion, which was 60-95% of the
      contralateral hand. This surgical procedure has few complications and is
      considered reliable.

PMID- 26296417
TI  - [Ligament reconstruction for lunotriquetral instability using a distally based
      strip of the extensor carpi ulnaris tendon].
AB  - OBJECTIVE: Stabilization of the lunotriquetral junction. INDICATIONS: Dynamic and
      static chronic instability without fixed dislocation of the carpals.
      CONTRAINDICATIONS: Chronically fixed dislocation of the carpals, ulnar impaction
      syndrome, osteoarthritis of the joint between hamate and triquetrum and other
      parts of the wrist joint, rheumatoid arthritis, chondrocalcinosis. SURGICAL
      TECHNIQUE: Restoration of the palmar portion of the lunotriquetral ligament using
      a distally based strip of the extensor carpi ulnaris tendon with temporary
      fixation of the lunotriquetral junction with K-wires. POSTOPERATIVE MANAGEMENT:
      Immobilization for 8 weeks with a radial cast that includes the first
      metacarpophalangeal joint. Removal of the K-wires after 8 weeks and exercise.
      RESULTS: The procedure with rare complications reliably restores stability of the
      lunotriquetral junction. Reduction of grip strength, pain during exercise, and a
      reduced range of motion persist. Overall, the results are predominantly good and
      excellent.

PMID- 26296418
TI  - [Medial patellofemoral ligament reconstruction using quadriceps tendon].
AB  - OBJECTIVE: Stabilization of the patella by medial patellofemoral ligament (MPFL)
      reconstruction. INDICATIONS: Recurrent lateral patella instability with chronic
      weakening of the MPFL. CONTRAINDICATIONS: Femoropatellar cartilage defects ICRS
      grade 3 degrees  or higher. Tuberositas Tibiae Trochlear Groove Index (TTTG) >20
      mm. Lateral hypercompression of the patella without instability. SURGICAL
      TECHNIQUE: A 3 cm transverse skin incision at the superomedial edge of the
      patella in 90 degrees  of flexion. Longitudinal incision of the prepatellar bursa
      and exposure of the quadriceps tendon. Preparation of a flat tendon strip with a
      length of 8 cm, a width of 10 mm, and a thickness of 3 mm, leaving the attachment
      at the patella intact. Flipping of the tendon strip and passing of the graft
      through a tunnel underneath the prepatellar tissue at the medial edge of the
      patella. Passing of the graft in layer two of the medial joint capsule just below
      the fascia (layer 1) and the vastus medialis. Fixation of the graft in a bone
      tunnel, drilled in the femoral insertion site of the native MPFL using a
      biodegradable interference screw. POSTOPERATIVE MANAGEMENT: Patella centralizing
      brace for 4 weeks with range of motion (ROM) 0/0/90 degrees , 20 kg of partial
      weight bearing for 3 weeks. Full weight-bearing according to pain starting from
      week 4 postoperatively. ROM up to 90 degrees  of flexion directly
      postoperatively. Free ROM starting from week 6 postoperatively. Stationary
      cycling 6 weeks postoperatively. Swimming and running after 10 months. Return to
      pivoting sports after 4-5 months. RESULTS: A total of 17 patients (7 men and 10
      women; average age 21.5 years +/-3.9 years, average BMI 22.6 +/-3.9) were treated
      using this technique between March 2011 and November 2012. Only patients with at
      least one recurrent patella dislocation following conservative treatment were
      included. Patient satisfaction 12 months postoperatively was very high. Overall,
      94.1 % would undergo the procedure again and 94.1 % were very satisfied with the
      cosmetic result. Significant improvement in Lysholm score 6, 12, and 24 months
      postoperatively (p < 0.05). Free ROM in 94.1 % of cases 12 months
      postoperatively. The Kujala score was reported to be 89 (+/-7.1) 12 months
      following surgery. No redislocation occurred during the 24 months following
      surgery.

PMID- 26296419
TI  - The overwhelming use of rat models in nerve regeneration research may compromise
      designs of nerve guidance conduits for humans.
AB  - Rats are not the best model for the evolving complexities we face in designing
      nerve repair strategies today. The development of effective nerve guidance
      conduits for nerve regeneration is severely limited by the rat sciatic nerve
      model as the almost exclusive research model in academia. An immense effort is
      underway to develop an alternative to autologous nerve grafts for the repair of
      nerve defects, aiming particularly at larger gap repairs of 5-30 cm or more. This
      must involve combinations of ever more complex components, which in the vast
      majority of cases begin their testing in the rat model. Three major problems are
      at play: (1) The majority of nerve regeneration data is now being generated in
      the rat, which is likely to skew treatment outcomes and lead to inappropriate
      evaluation of risks and benefits. (2) The rat is a particularly poor model for
      the repair of human critical gap defects due to both its small size and its
      species-specific neurobiological regenerative profile. (3) Translation from rat
      to human has proven unreliable for nerve regeneration, as for many other
      applications. We explore each of these facets and their implications, in order to
      highlight the need for appropriate awareness in animal model selection when
      translating nerve regeneration modalities of ever-increasing complexity-from
      relatively simple devices to drug-device-biologic combinations. 

PMID- 26296420
TI  - Muscle-specificity of age-related changes in markers of autophagy and
      sphingolipid metabolism.
AB  - Our previous findings indicate that the gastrocnemius muscle of aging rats
      exhibits impairments of muscle quality (force/unit muscle tissue) and autophagy
      and increased sarcoplasmic reticulum stress. The purpose of this study was to
      examine age-related changes in soleus muscle contractility and in markers of
      autophagy in the soleus and gastrocnemius muscles. We assessed in situ muscle
      force and size in the soleus muscle of adult (7-8 months) and aged (24-26 months)
      male, F344/BN rats. We used immunoblotting to compare abundance of markers of
      autophagy, sarcoplasmic reticulum (SR) stress and sphingolipid metabolism in the
      soleus and medial gastrocnemius (MG) muscles of these animals. Relative to
      adults, aged rats maintained soleus muscle quality and increased muscle size,
      resulting in increased tetanic force production. Immunoblotting revealed a
      general pattern of an age-related reduction of basal autophagy, despite increases
      in indicators of SR stress and upstream autophagic pathway activation in the MG.
      The MG also exhibited changes in markers of sphingolipid metabolism suggestive of
      increased muscle ceramide. Minimal age-related changes were observed in the
      soleus. The soleus maintains muscle mass and quality with age, and exhibits fewer
      age-related changes in markers of stress and autophagy than the MG. Based on
      these data, we suggest that maintenance of autophagy may preserve muscle quality
      by preventing excessive SR stress.

PMID- 26296421
TI  - Nifedipine and phenytoin induce matrix synthesis, but not proliferation, in
      intact human gingival connective tissue ex vivo.
AB  - Drug-induced gingival enlargement (DIGE) is a fibrotic condition that can be
      caused by the antihypertensive drug nifedipine and the anti-seizure drug
      phenytoin, but the molecular etiology of this type of fibrosis is not well
      understood and the role of confounding factors such as inflammation remains to be
      fully investigated. The aim of this study was to develop an ex vivo gingival
      explant system to allow investigation of the effects of nifedipine and phenytoin
      alone on human gingival tissue. Comparisons were made to the histology of human
      DIGE tissue retrieved from individuals with DIGE. Increased collagen,
      fibronectin, and proliferating fibroblasts were evident, but myofibroblasts were
      not detected in DIGE samples caused by nifedipine and phenytoin. In healthy
      gingiva cultured in nifedipine or phenytoin-containing media, the number of cells
      positive for p-SMAD2/3 increased, concomitant with increased CCN2 and periostin
      immunoreactivity compared to untreated explants. Collagen content assessed
      through hydroxyproline assays was significantly higher in tissues cultured with
      either drug compared to control tissues, which was confirmed histologically.
      Matrix fibronectin levels were also qualitatively greater in tissues treated with
      either drug. No significant differences in proliferating cells were observed
      between any of the conditions. Our study demonstrates that nifedipine and
      phenytoin activate canonical transforming growth factor-beta signaling, CCN2 and
      periostin expression, as well as increase collagen density, but do not influence
      cell proliferation or induce myofibroblast differentiation. We conclude that in
      the absence of confounding variables, nifedipine and phenytoin alter matrix
      homeostasis in gingival tissue explants ex vivo, and drug administration is a
      significant factor influencing ECM accumulation in gingival enlargement. 

PMID- 26296423
TI  - A Novel Method for Removing a Spinal Cord with Attached Cervical Ganglia from a
      Pediatric Decedent.
AB  - A diagnosis of child abuse is dependent on a comprehensive and accurate
      assessment of injury in the context of a thorough investigation. However,
      signatures of trauma are often subtle and interpretation can be very difficult.
      Recently, researchers have refocused their attention from the head to the neck in
      search of traumatic signatures of abusive head trauma. HCIFS has developed a
      technique to remove the cervical spinal cord with the ganglia attached that is
      less destructive and more time and cost efficient than alternative methods
      previously published. Once removed, the dorsal nerve roots and ganglia are
      evaluated for the presence of hemorrhage. The authors performed a small pilot
      study using the novel method to evaluate 20 decedents with a history of blunt
      force trauma and eight without a traumatic history. Fifteen of the traumatic
      deaths and two of the nontraumatic deaths were found to have dorsal nerve root
      and/or ganglia hemorrhage. 

PMID- 26296422
TI  - Robust Anti-viral Immunity Requires Multiple Distinct T Cell-Dendritic Cell
      Interactions.
AB  - Host defense against viruses and intracellular parasites depends on effector
      CD8(+) T cells, whose optimal clonal expansion, differentiation, and memory
      properties require signals from CD4(+) T cells. Here, we addressed the role of
      dendritic cell (DC) subsets in initial activation of the two T cell types and
      their co-operation. Surprisingly, initial priming of CD4(+) and CD8(+) T cells
      was spatially segregated within the lymph node and occurred on different DCs with
      temporally distinct patterns of antigen presentation via MHCI versus MHCII
      molecules. DCs that co-present antigen via both MHC molecules were detected at a
      later stage; these XCR1(+) DCs are the critical platform involved in CD4(+) T
      cell augmentation of CD8(+) T cell responses. These findings delineate the
      complex choreography of cellular interactions underlying effective cell-mediated
      anti-viral responses, with implications for basic DC subset biology, as well as
      for translational application to the development of vaccines that evoke optimal T
      cell immunity.

PMID- 26296424
TI  - SNARE Complex Dysfunction: A Unifying Hypothesis for Schizophrenia.

PMID- 26296425
TI  - Pathologic Implications for Microtubule-Associated Protein 2 in Schizophrenia
      Primary Auditory Cortex.

PMID- 26296426
TI  - Mitsunobu Reaction: A Versatile Tool for PEG End Functionalization.
AB  - The Mitsunobu reaction can be efficiently used for the transformation of
      poly(ethylene glycol) (PEG) terminal OH group(s) into a variety of functions. In
      comparison to more classical approaches of PEG functionalization, the main
      advantage of the Mitsunobu reaction attains to the fact that in one step, with no
      detrimental effect on PEG integrity (e.g., chain cleavage). Here, its
      quantitative conversion is demonstrated into derivatives that, either directly or
      after deprotection, are amenable to (bio)conjugation reactions: azides (Huisgen
      cycloaddition), aldehydes, primary amines (Schiff base formation and reduction),
      thiols, and N-oxymaleimide (Michael-type addition). Therefore this reaction is
      proposed as a general tool for the preparation of functionalities for the purpose
      of PEGylation, and more generally for (bio)conjugation purposes. 

PMID- 26296427
TI  - Gender related Long-term Differences after Open Infrainguinal Surgery for
      Critical Limb Ischemia.
AB  - OBJECTIVE: The role of gender on long-term infrainguinal open surgery outcomes
      still remains uncertain in critical limb ischemia patients. The aim of this study
      is to evaluate the gender-specific differences in patient characteristics and
      long-term clinical outcomes in terms of survival, primary patency and limb
      salvage among patients undergoing infrainguinal open surgery for CLI. MATERIAL
      AND METHODS: All consecutive patients undergoing infrainguinal open surgery for
      critical limb ischemia between 2003 and 2012 were included. Survival, limb
      salvage and primary patency rates were assessed. Independent outcome determinants
      were identified by the Cox proportional hazard ratio using age and gender as
      adjustment factors. RESULTS: 584 patients (269 women and 315 men, mean age 76 and
      71 years respectively) underwent 658 infrainguinal open surgery (313 in women and
      345 in men). Survival rate at 6 years was lower among women compared to men with
      53.5% vs 70.9% (p < 0.001). The same applied to primary patency (35.9% vs 52.4%,
      p < 0.001) and limb salvage (54.3% vs 81.1%, p < 0.001) at 6 years. Female-gender
      was an independent factor predicting death (hazard ratio 1.50), thrombosis
      (hazard ratio 2.37) and limb loss (hazard ratio 7.05) in age and gender-adjusted
      analysis. CONCLUSION: Gender-related disparity in critical limb ischemia open
      surgical revascularization outcomes still remains.

PMID- 26296428
TI  - Neural involvement in endometriosis: Review of anatomic distribution and
      mechanisms.
AB  - Endometriosis (EM) is an infrequent cause of peripheral neuropathy, most commonly
      sciatic. Perineural spread has recently been introduced as an alternate
      explanation for cases of lumbosacral or sciatic nerve EM. We performed a
      literature review to collect all reported cases of peripheral and central nervous
      system EM in search of anatomic patterns of involvement; potentially to support
      the perineural spread theory. If available, intraneural invasion and presence of
      peritoneal EM were recorded. The search revealed 83 articles describing 365 cases
      of somatic peripheral nervous EM and 13 cases of central nervous EM. The most
      frequently involved site was the sacral plexus (57%, n = 211), followed by the
      sciatic nerve (39%, n = 140). Other nerves were reported in significantly smaller
      numbers. Ninety seven percent (97%, n = 355) of peripheral nerve cases presented
      with pain, 20% (n = 72) reported weakness and 31% (n = 114), numbness. Thirty
      four percent (34%, n = 38) had solely intraneural EM of which 89% (n = 33) had no
      peritoneal EM (percentage based on available information). In the central nervous
      system, the conus medullaris and/or cauda equina constituted the majority of
      cases with 54% (n = 7). Apart from perineural spread, other discussed mechanisms
      include retrograde menstruation with peritoneal seeding, hematogenous and
      lymphogenous spread, stem cell implantation either hematogenously or via
      retrograde menstruation with subsequent EM differentiation, and coelomic or
      Mullerian duct metaplasia. We believe this literature review supports perineural
      spread as an alternate mechanism for EM of nerve, particularly the subgroup with
      intraneural EM and without peritoneal disease.

PMID- 26296429
TI  - Microsurgery and endovascular treatment of posterior inferior cerebellar artery
      aneurysms.
AB  - Aneurysms located on the posterior inferior cerebellar artery are rare, and
      treatment guidelines for them have not yet been established. In this paper, we
      present the results of a retrospective study which analyzes the management and
      treatment of 15 patients with posterior inferior cerebellar artery aneurysms from
      2004 to 2013. The aneurysms were ruptured and presented with a subarachnoid
      hemorrhage. Of the 15 aneurysms, ten were of saccular, three fusiform, and two
      were dissecting. Computed tomography angiography or digital subtraction
      angiography revealed other aneurysms or intracerebral artery hypoplasia in seven
      patients. Either surgical or endovascular treatment was performed depending on
      the localization and morphology of the aneurysm. Six aneurysms were coiled, and
      surgery was performed in nine cases. Of the nine surgically treated patients, six
      (75%) had good outcomes. Of the six patients treated using endovascular
      procedures, three patients (50%) recovered. Patient outcomes were classified
      using the Hunt&Hess scale. Patients with Hunt&Hess 1-3 recovered without a
      neurological deficit. On the other hand, patients with Hunt&Hess 4-5 had a risk
      of up to 93% of death or a poor outcome. In two cases of endovascular and in two
      cases before any therapy, aneurysmal rebleeding occurred and resulted in
      deterioration of clinical state of the patient and a poor prognosis with high
      risk of death. This study shows the necessity of acute treatment of posterior
      inferior cerebellar artery aneurysm, of thorough diagnostic, and of
      interdisciplinary cooperation.

PMID- 26296430
TI  - [Clinical and immunological profile of HIV-infected patients at the initiation of
      antiretroviral therapy in Douala].
AB  - The aim of this study was to describe the clinical and immunological profile of
      patients infected with HIV after initiation of antiretroviral therapy.
      Sociodemographic characteristics, clinical and immunological patients were
      recorded. Chi square test and Mann-Whitney were used to compare variables. The
      multivariate regression model identified risk factors. So that, 936 (56.2%)
      patients were in stages III and IV of the WHO and 65.2% at an advanced stage of
      the disease. Factors associated with initiation at an advanced stage, were male
      sex (p = 0.007) and time to diagnosis (p = 0.005). In 2/3 cases, treatment is
      started at an advanced stage of disease. It is therefore important to intensify
      awareness campaigns for early detection and encourage patients to ensure regular
      medical follow-up screening.

PMID- 26296431
TI  - Dendronized Hyperbranched Macromolecules: Soft Matter with a Novel Type of
      Segmental Distribution.
AB  - Dendronization of a hyperbranched polyester with different generation dendrons
      leads to pseudo-dendritic structures. The hyperbranched core is modified by the
      divergent coupling of protected monomer units to the functional groups. Compared
      to dendrimers, the synthetic effort is significantly less, but the properties are
      very close to those of high-generation dendrimers. The number of functional
      groups, molar mass, and rheology behavior even in the early generation (G1-G4)
      pseudo-dendrimers strongly resembles the behavior of dendrimers in higher
      generations (G5-G8). Comparison of the segmental and internal structure with
      perfect dendrimers is performed using SANS, dynamic light scattering and
      viscosity analysis, microscopy and molecular dynamics simulation. The
      interpretation of the results reveals unique structural characteristics arising
      from lower segmental density of the core, which turns into a soft nano-sphere
      with a smooth surface even in the first generation. 

PMID- 26296432
TI  - Oral health of schoolchildren in Western Australia.
AB  - BACKGROUND: The West Australian School Dental Service (SDS) provides free,
      statewide, primary dental care to schoolchildren aged 5-17 years. This study
      reports on an evaluation of the oral health of children examined during the 2014
      calendar year. METHODS: Children were sampled, based on their date of birth, and
      SDS clinicians collected the clinical information. Weighted mean values of caries
      experience were presented. Negative binomial regression modelling was undertaken
      to test for factors of significance in the rate of caries occurrence. RESULTS:
      Data from children aged 5-15 years were used (girls = 4616, boys = 4900). Mean
      dmft (5-10-year-olds), 1.42 SE 0.03; mean DMFT (6-15-year-olds), 0.51 SE 0.01.
      Negative binomial regression model of permanent tooth caries found higher rates
      of caries in children who were from non-fluoridated areas (RR 2.1); Aboriginal
      (RR 2.4); had gingival inflammation (RR 1.5); lower ICSEA level (RR 1.4); and
      recalled at more than 24-month interval (RR 1.8). CONCLUSIONS: The study
      highlighted poor dental health associated with living in non-fluoridated areas,
      Aboriginal identity, poor oral hygiene, lower socioeconomic level and having
      extended intervals between dental checkups. Timely assessments and preventive
      measures targeted at groups, including extending community water fluoridation,
      may assist in further improving the oral health of children in Western Australia.

PMID- 26296433
TI  - Undirected health IT implementation in ambulatory care favors paper-based
      workarounds and limits health data exchange.
AB  - BACKGROUND: The adoption and use of health information technology (IT) continues
      to grow around the globe. In Switzerland, the government nor professional
      associations have to this day provided incentives for health IT adoption.
      OBJECTIVE: We aim to assess the proportion of physicians who are routinely
      working with electronic health data and describe to what extent physicians
      exchange electronic health data with peers and other health care providers.
      Additionally, we aim to estimate the effect of physicians' attitude towards
      health IT on the adoption of electronic workflows. METHODS: Between May and July
      2013, we conducted a cross-sectional survey of 1200 practice based physicians in
      Switzerland. Respondents were asked to report on their technical means and where
      applicable their paper-based workarounds to process laboratory data, examination
      results, referral letters and physician's letters. Physicians' view of barriers
      and facilitators towards health IT use was determined by a composite score.
      RESULTS: A response rate of 57.1% (n=685) was reached. The sample was considered
      to be representative for physicians in Swiss ambulatory care. 35.2% of the
      respondents documented patients' health status with the help of a longitudinal
      semi-structured electronic text record generated by one or more encounters in the
      practice. Depending on the task within a workflow, around 11-46% of the
      respondents stated to rely on electronic workflow practices to process laboratory
      and examination data and dispatch referral notes and physician's letters. The
      permanent use of electronic workflow processes was infrequent. Instead,
      respondents reported paper-based workarounds affecting specific tasks within a
      workflow. Physicians' attitude towards health IT was significantly associated
      with the adoption of electronic workflows (OR 1.04-1.31, p<0.05), but the effect
      sizes of factors related to the working environment (e.g., regional factors,
      medical specialty, type of practice) were larger. CONCLUSION: At present, only a
      few physicians in Swiss ambulatory care routinely work with electronic health
      data. Until more of their peers participate in electronic exchange of structured
      clinical information, most physicians will continue to stay in paper-based
      systems and workarounds. The survey found that physicians with a positive
      attitude towards health IT were more likely to adopt electronic workflows, but
      the impact is minor. It will likely be necessary to introduce financial
      incentives and develop national standards in order to promote the adoption by a
      critical mass of practicing clinicians.

PMID- 26296434
TI  - Linkages between observed, modeled Saharan dust loading and meningitis in Senegal
      during 2012 and 2013.
AB  - The Sahara desert transports large quantities of dust over the Sahelian region
      during the Northern Hemisphere winter and spring seasons (December-April). In
      episodic events, high dust concentrations are found at the surface, negatively
      impacting respiratory health. Bacterial meningitis in particular is known to
      affect populations that live in the Sahelian zones, which is otherwise known as
      the meningitis belt. During the winter and spring of 2012, suspected meningitis
      cases (SMCs) were with three times higher than in 2013. We show higher surface
      particular matter concentrations at Dakar, Senegal and elevated atmospheric dust
      loading in Senegal for the period of 1 January-31 May during 2012 relative to
      2013. We analyze simulated particulate matter over Senegal from the Weather
      Research and Forecasting (WRF) model during 2012 and 2013. The results show
      higher simulated dust concentrations during the winter season of 2012 for
      Senegal. The WRF model correctly captures the large dust events from 1 January-31
      March but has shown less skill during April and May for simulated dust
      concentrations. The results also show that the boundary conditions are the key
      feature for correctly simulating large dust events and initial conditions are
      less important. 

PMID- 26296435
TI  - Normative body dissatisfaction and eating psychopathology in teenage girls: the
      impact of inflexible eating rules.
AB  - PURPOSE: Adolescence has been considered a critical time for the development of
      body image-related difficulties and disordered eating behaviours, especially in
      females. Although adherence to eating rules has been linked to disordered eating,
      literature has not yet explored how the inflexible subscription to those rules
      impacts on eating psychopathology. Therefore, the aim of the current study was to
      explore whether inflexible eating impacts on the relationships between weight and
      body image-related variables, and disordered eating. METHODS: Participated in
      this study are 497 female adolescents from the community, aged between 14 and 18
      years old, who completed self-report measures. RESULTS: Results revealed that the
      majority of the participants were dissatisfied with their weight and body shape.
      Moreover, 6.64 % of the participants demonstrated severe eating psychopathology.
      A path analysis revealed that BMI, body dissatisfaction and social comparisons
      based on physical appearance impact on disordered eating behaviours, through the
      mechanism of inflexible adherence to eating rules. This model explained 52 % of
      eating psychopathology's variance. CONCLUSIONS: Findings highlight the relevance
      of body image-related difficulties in adolescence and additionally they emphasise
      the importance of promoting more flexible attitudes towards eating in prevention
      and intervention programmes with female adolescents.

PMID- 26296437
TI  - Nano-assembly of nanodiamonds by conjugation to actin filaments.
AB  - Fluorescent nanodiamonds (NDs) are remarkable objects. They possess unique
      mechanical and optical properties combined with high surface areas and
      controllable surface reactivity. They are non-toxic and hence suited for use in
      biological environments. NDs are also readily available and commercially
      inexpensive. Here, the exceptional capability of controlling and tailoring their
      surface chemistry is demonstrated. Small, bright diamond nanocrystals (size ~30
      nm) are conjugated to protein filaments of actin (length ~3-7 um). The
      conjugation to actin filaments is extremely selective and highly target-specific.
      These unique features, together with the relative simplicity of the conjugation
      targeting method, make functionalised nanodiamonds a powerful and versatile
      platform in biomedicine and quantum nanotechnologies. Applications ranging from
      using NDs as superior biological markers to, potentially, developing novel bottom
      up approaches for the fabrication of hybrid quantum devices that would bridge
      across the bio/solid-state interface are presented and discussed.

PMID- 26296436
TI  - Catechol-O-methyltransferase activity in erythrocytes from patients with eating
      disorders.
AB  - PURPOSE: Abnormal feeding has been linked to disruptions in brain dopaminergic
      activity and recent studies have assessed the role of catechol-O
      methyltransferase (COMT) in eating disorders. This is the first study to quantify
      the soluble catechol-O-methyltransferase (S-COMT) activity in erythrocytes from
      patients with anorexia nervosa (AN), bulimia nervosa (BN) and binge-eating
      disorder (BED) and the first study at all to evaluate the COMT on patients with
      BED. METHODS: Forty blood samples from patients with AN, BN and BED and healthy
      controls were drawn to evaluate S-COMT activity in erythrocytes by high
      performance liquid chromatography and mass spectrometry. Since several patients
      were being treated with fluoxetine 20 mg, they were included in a different group
      (BN MED and BED MED). Liver homogenates from rats were used to evaluate baseline
      S-COMT activity in the presence of fluoxetine by the same in vitro procedures and
      assays. RESULTS: Erythrocyte S-COMT activity (pmol/mg prt/h) was significantly
      increased in patients with BN and BED (41.3 +/- 6.8 and 41.4 +/- 14,
      respectively) compared to control group (25.3 +/- 9.7). In fluoxetine-treated
      patients with BN, S-COMT activity (15.9 +/- 8.8) was decreased compared to the
      other BN group; however, in BED group, the difference between BED MED and BED was
      not observed. In patients with AN, no significant difference was found compared
      to controls. CONCLUSION: Patients with BN and BED presented higher S-COMT
      activity in erythrocytes, which is in agreement with previous studies on the
      literature addressing the high-activity COMT allele, Val158, as risk factor for
      eating disorders. Although in fluoxetine-treated patients with BN the activity of
      S-COMT was similar to the controls, this is not explained by a direct interaction
      between fluoxetine and S-COMT as verified in in vitro assays.

PMID- 26296438
TI  - Xenobiotic and Immune-Relevant Molecular Biomarkers in Harbor Seals as Proxies
      for Pollutant Burden and Effects.
AB  - Harbor seals are exposed to increasing pressure caused by anthropogenic
      activities in their marine environment. Persistent organic pollutants (POPs) and
      trace elements are hazardous contaminants that accumulate in tissues of harbor
      seals. POPs and trace elements can negatively affect the immune-system and have
      been reported, e.g., to increase susceptibility to viral infections in seals.
      Biomarkers of the xenobiotic metabolism, cytokines, and heat-shock protein as
      cell mediators of the immune-system were established to evaluate the impact of
      environmental stressors on harbor seals. Harbor seals (n = 54) were captured on
      sandbanks in the North Sea during 2009-2012. Health assessments, including
      hematology, were performed, and RNAlater blood samples were taken and analyzed
      using quantitative polymerase chain reaction. Normalized transcript copy numbers
      were correlated to hematology and POP concentration in blood and trace metals in
      blood and fur. A significant correlation between xenobiotic markers and
      contaminant burden was found. Significant interrelationships between markers and
      POP compounds, as well as with season, weight, and hematology values, indicate
      that biomarkers reflect pollutant exposure and effects. A significant
      relationship between cortisol levels and heat-shock protein expression was
      observed indicating stress experienced during restraint of the seals. Interleukin
      10 transcription showed significant correlations with trace elements in fur
      pointing toward immune regulatory effects of metal exposure. The molecular
      markers prove to be an important noninvasive tool that reflects contaminant
      exposure and the impact of anthropogenic stressors in seal species. The
      connection between interleukin-2, xenobiotic markers, and pollutants may indicate
      immune suppression in animals exposed to contaminants with subsequent
      susceptibility to inflammatory disease.

PMID- 26296439
TI  - [Lipid peroxidation in the lymphocyte membrane and protein oxidation in the serum
      of elderly people. Are they potential markers of frailty and dependence?
      Preliminary results].
AB  - OBJECTIVE: To study the relationships between lipid peroxidation of the
      lymphocyte membrane, protein oxidation and different markers of frailty and
      dependence. METHODS: The sample consisted of 15 elderly patients in an
      intermediate and long-term care center, who had not suffered any acute process
      recently. The geriatric assessment included, functional capacity (Barthel and
      Lawton indexes), comorbidity (Charlson index), and cognitive function (Mini
      Mental State Examination of Folstein). The frailty was estimated by the Hospital
      Admission Risk Profile (high risk of frailty 4-5 points, intermediate/low 0-3
      points) and Frailty Scale of Rockwood (mild frailty<6, intermediate
      frailty/severe>=6). Lipid peroxidation was studied by determination of conjugated
      dienes and trienes. Analysis of protein oxidation was performed by determining
      malondialdehyde bound to plasma proteins, corrected by total protein
      quantification. RESULTS: Elderly patients at high risk of frailty according to
      Hospital Admission Risk Profile presented mean values of conjugated dienes of
      7.94+/-1.32%, trienes of 1.75+/-0.51%, and malondialdehyde bound to plasma
      proteins of 141.9+/-27.3nmol/g. In the group of intermediate/low risk, these
      values were 4.96+/-2.77% (P=.035), 1.37+/-0.78% (P=.337) and 96.4+/-31.5nmol/g
      (P=.022), respectively. In those with intermediate/severe frailty according to
      the Frailty Scale of Rockwood, these values were 7.06+/-2.18%; 1.73+/-0.50% and
      119.6+/-37.9nmol/g, respectively, and in those with mild frailty 2.56+/-1.48%
      (P=014); 0.61+/-0.58% (P=020) and 173.2+/-51.9nmol/g (P=.144), respectively.
      There was good correlation between the Hospital Admission Risk Profile score and
      malondialdehyde bound to plasma proteins (r=0.70; P=01) and between the Frailty
      Scale of Rockwood score and conjugated dienes (r=0.65; P=01). CONCLUSIONS:
      Elderly patients with a higher degree of frailty appear to have greater levels of
      lipid peroxidation, which could be considered a marker of frailty.

PMID- 26296440
TI  - Adverse Childhood Experiences: Expanding the Concept of Adversity.
AB  - INTRODUCTION: Current knowledge of Adverse Childhood Experiences (ACEs) relies on
      data predominantly collected from white, middle- / upper-middle-class
      participants and focuses on experiences within the home. Using a more
      socioeconomically and racially diverse urban population, Conventional and
      Expanded (community-level) ACEs were measured to help understand whether
      Conventional ACEs alone can sufficiently measure adversity, particularly among
      various subgroups. METHODS: Participants from a previous large, representative,
      community-based health survey in Southeast Pennsylvania who were aged >=18 years
      were contacted between November 2012 and January 2013 to complete another phone
      survey measuring ACEs. Ordinal logistic regression models were used to test
      associations between Conventional and Expanded ACEs scores and demographic
      characteristics. Analysis was conducted in 2013 and 2014. RESULTS: Of 1,784
      respondents, 72.9% had at least one Conventional ACE, 63.4% at least one Expanded
      ACE, and 49.3% experienced both. A total of 13.9% experienced only Expanded ACEs
      and would have gone unrecognized if only Conventional ACEs were assessed. Certain
      demographic characteristics were associated with higher risk for Conventional
      ACEs but were not predictive of Expanded ACEs, and vice versa. Few adversities
      were associated with both Conventional and Expanded ACEs. CONCLUSIONS: To more
      accurately represent the level of adversity experienced across various
      sociodemographic groups, these data support extending the Conventional ACEs
      measure.

PMID- 26296441
TI  - Adolescent Dating Violence in Context.

PMID- 26296442
TI  - Beyond the Individual Level: Novel Approaches and Considerations for Multilevel
      Adolescent Dating Violence Prevention.

PMID- 26296443
TI  - A First Look at Gender Inequality as a Societal Risk Factor for Dating Violence.
AB  - INTRODUCTION: One of ten U.S. high school students is a victim of adolescent
      dating violence (ADV). Understanding ADV risk factors guides prevention efforts;
      however, research examining community- and societal-level risk factors is scant.
      Societal gender inequality is a known risk factor for violence against women, but
      has yet to be explored in relation to ADV. This study aims to determine whether
      the Gender Inequality Index (GII) correlates with levels of physical and sexual
      ADV victimization across U.S. states. METHODS: State-representative prevalence
      rates of self-reported physical and sexual ADV victimization were obtained from
      the 2013 Youth Risk Behavior Survey. The state GII includes five indicators: (1)
      maternal mortality; (2) adolescent birth rate; (3) government representation; (4)
      educational attainment; and (5) labor force participation. Pearson correlation
      coefficients determined the association between physical and sexual ADV
      victimization, the GII, and GII indicators. Analyses were conducted in August
      2014. RESULTS: Among U.S. states, the prevalence of physical ADV victimization in
      2013 ranged from 7.0% to 14.8%, and the prevalence of sexual ADV victimization
      ranged from 7.8% to 13.8%. The GII was significantly associated with the state
      prevalence of female physical ADV victimization (r=0.48, p<0.01) but not female
      sexual ADV victimization. Neither physical nor sexual male ADV victimization was
      associated with the GII. CONCLUSIONS: This exploratory study suggests that gender
      inequality may be a societal-level risk factor for female physical ADV
      victimization. As ADV prevention strategies are implemented at the state level,
      further research examining the effect of gender inequality on ADV is needed.

PMID- 26296444
TI  - Neighborhood Factors and Dating Violence Among Youth: A Systematic Review.
AB  - CONTEXT: The purpose of this review is to summarize the empirical research on
      neighborhood-level factors and dating violence among adolescents and emerging
      adults to guide future research and practice. EVIDENCE ACQUISITION: In 2015, a
      total of 20 articles were identified through a search of the literature using
      PubMed. Eligible articles included those that (1) had been published in a peer
      reviewed journal since 2005; (2) reported a measure of association between at
      least one neighborhood-level factor and dating violence; and (3) had a study
      population of youth aged <26 years. We abstracted information about the studies,
      including measurement of dating violence and neighborhood factors, and measures
      of effect. EVIDENCE SYNTHESIS: Results were summarized into three categories
      based on the aspect of neighborhood that was the focus of the work: demographic
      and structural characteristics (n=11); neighborhood disorder (n=12); and social
      disorganization (n=8). There was some evidence to suggest that neighborhood
      disadvantage is associated with dating violence, but very little evidence to
      suggest that residence characteristics (e.g., racial heterogeneity) are
      associated with dating violence. Results do suggest that perceived neighborhood
      disorder is associated with physical dating violence perpetration, but do not
      suggest that it is associated with physical dating violence victimization. Social
      control and community connectedness are both associated with dating violence, but
      findings on collective efficacy are mixed. CONCLUSIONS: Existing research
      suggests that neighborhood factors may be associated with dating violence.
      However, there is a limited body of research on the neighborhood context of
      dating violence, and more rigorous research is needed.

PMID- 26296445
TI  - Substance Use and Physical Dating Violence: The Role of Contextual Moderators.
AB  - INTRODUCTION: Theoretic models suggest that associations between substance use
      and dating violence perpetration may vary in different social contexts, but few
      studies have examined this proposition. The current study examined whether social
      control and violence in the neighborhood, peer, and family contexts moderate the
      associations between substance use (heavy alcohol use, marijuana, and hard drug
      use) and adolescent physical dating violence perpetration. METHODS: Adolescents
      in the eighth, ninth, and tenth grades completed questionnaires in 2004 and again
      four more times until 2007 when they were in the tenth, 11th, and 12th grades.
      Multilevel analysis was used to examine interactions between each substance and
      measures of neighborhood, peer, and family social control and violence as within
      person (time-varying) predictors of physical dating violence perpetration across
      eighth through 12th grade (N=2,455). Analyses were conducted in 2014. RESULTS:
      Physical dating violence perpetration increased at time points when heavy alcohol
      and hard drug use were elevated; these associations were weaker when neighborhood
      social control was higher and stronger when family violence was higher. Also, the
      association between heavy alcohol use and physical dating violence perpetration
      was weaker when teens had more-prosocial peer networks and stronger when teens'
      peers reported more physical dating violence. CONCLUSIONS: Linkages between
      substance use and physical dating violence perpetration depend on substance use
      type and levels of contextual violence and social control. Prevention programs
      that address substance use-related dating violence should consider the role of
      social contextual variables that may condition risk by influencing adolescents'
      aggression propensity.

PMID- 26296446
TI  - Predicting Adolescent Dating Violence Perpetration: Role of Exposure to Intimate
      Partner Violence and Parenting Practices.
AB  - INTRODUCTION: Exposure to adult intimate partner violence (IPV) places youth at
      risk for a range of outcomes, including perpetration of adolescent dating
      violence (ADV). However, there is variability in the effect of IPV exposure, as
      many youth who are exposed to IPV do not go on to exhibit problems. Thus,
      research is needed to examine contextual factors, such as parenting practices, to
      more fully explain heterogeneity in outcomes and better predict ADV perpetration.
      The current research draws from a multisite study to investigate the predictive
      power of IPV exposure and parenting practices on subsequent ADV perpetration.
      METHODS: Participants included 417 adolescents (48.7% female) drawn from middle
      schools in high-risk, urban communities. IPV exposure, two types of parenting
      practices (positive parenting/involvement and parental knowledge of their child's
      dating), and five types of ADV perpetration (threatening behaviors,
      verbal/emotional abuse, relational abuse, physical abuse, and sexual abuse) were
      assessed at baseline (2012) and approximately 5 months later (2013) via
      adolescent report. Analyses (conducted in 2015) used a structural equation
      modeling approach. RESULTS: Structural models indicated that IPV exposure was
      positively related only to relational abuse at follow-up. Further, adolescents
      who reported parents having less knowledge of dating partners were more likely to
      report perpetrating two types of ADV (physical and verbal/emotional abuse) at
      follow-up. Analyses did not demonstrate any significant interaction effects.
      CONCLUSIONS: Results fill a critical gap in understanding of important targets to
      prevent ADV in middle school and highlight the important role that parents may
      play in ADV prevention.

PMID- 26296447
TI  - The Synergy of Family and Neighborhood on Rural Dating Violence Victimization.
AB  - INTRODUCTION: Rural adolescents are at high risk for dating violence
      victimization (DVV), which has serious negative consequences. Understanding more
      about the conditions that increase DVV risk for rural adolescents is needed to
      inform prevention efforts. In response to calls for examining the influence of
      upper levels of the social ecology on adolescent dating violence, this study
      examined whether associations between the family context and physical DVV were
      conditioned by the characteristics of the neighborhoods in which the family
      resided. METHODS: Data were from a multi-wave longitudinal study of 3,236 rural
      adolescents nested in 65 block groups, which defined neighborhoods. Data were
      collected between 2003 and 2005. Multilevel growth curve modeling was conducted
      in 2014 to test hypothesized synergistic effects of the family and neighborhood
      on trajectories of physical DVV from grade 8 to 12. RESULTS: Low parental
      closeness was a DVV risk in residentially stable (p<0.001), but not unstable,
      neighborhoods. Family aggression was a DVV risk, regardless of neighborhood
      characteristics (p=0.001). Low parental monitoring and rule setting were not DVV
      risks and their effects were not moderated by neighborhood characteristics.
      Neighborhood ethnic heterogeneity was significantly (p<0.05) positively
      associated with DVV, but neighborhood economic disadvantage, social
      disorganization, and violence were not associated with DVV. None of the effects
      varied by sex of the adolescent, across time (grade), or by the combination of
      sex and time. CONCLUSIONS: Findings demonstrate the importance of considering the
      family and neighborhood, and particularly their synergistic effects in efforts to
      prevent adolescent DVV.

PMID- 26296448
TI  - Safety and Tolerability of Biphasic Immediate-Release/Extended-Release
      Oxycodone/Acetaminophen Tablets: Analysis of 11 Clinical Trials.
AB  - OBJECTIVES: To characterize the safety of immediate-release (IR)/extended-release
      (ER) oxycodone (OC)/acetaminophen (APAP). METHODS: Data were assessed from 9
      phase 1 trials in healthy volunteers and recreational users of prescription
      opioids (N = 405), including 5 single-dose and 3 multidose open-label
      pharmacokinetic studies of IR/ER OC/APAP and active comparators; and 1
      randomized, controlled, single-dose human abuse potential (HAP) study comparing
      IR/ER OC/APAP, IR OC/APAP, and placebo in recreational users of opioids; and 2
      phase 3 trials (N = 701) including a 48-hour placebo-controlled safety and
      efficacy study in patients with moderate to severe postbunionectomy pain with a
      14-day open-label safety extension and a long-term (<= 35 days) open-label safety
      study in patients with chronic osteoarthritis pain or chronic low back pain.
      RESULTS: Adverse events (AEs) experienced by >= 10% of participants receiving
      IR/ER OC/APAP in all trials were pruritus, nausea, vomiting, dizziness, headache,
      and somnolence; these AEs occurred with similar frequency for equianalgesic doses
      of IR OC/APAP and IR OC but less frequently for IR tramadol HCl/APAP. In the HAP
      study, crushing IR/ER or IR OC/APAP tablets did not increase frequency of AEs.
      Constipation was experienced by < 10% of participants receiving IR/ER OC/APAP. No
      serious (SAE) or severe AEs were reported in phase 1 trials. In phase 3 trials of
      8 reported SAEs, only 1 treatment-related SAE (hypersensitivity to placebo)
      required treatment discontinuation. No clinically meaningful changes in vital
      signs, oxygen saturation, electrocardiograms, or laboratory values were reported.
      CONCLUSIONS: Safety and tolerability of IR/ER OC/APAP are similar to other low
      dose opioid/APAP analgesics.

PMID- 26296449
TI  - Tracking malaria transmission at the antenatal clinic.

PMID- 26296451
TI  - Language Impairment in Adolescents With Sydenham Chorea.
AB  - BACKGROUND: Neuropsychiatric comorbidities are frequent in Sydenham chorea.
      However, cognitive impairment in Sydenham chorea has not been sufficiently
      described. The objective of this study was to evaluate expressive and receptive
      language deficits in adolescents with Sydenham chorea. METHODS: Twenty patients
      with Sydenham chorea were compared with 20 patients with rheumatic fever without
      chorea and 20 healthy controls. Participants were matched for age and gender.
      Participants were assessed with verbal fluency tasks (phonemic and semantic) and
      with verbal comprehension tasks (Token Test). Patients with Sydenham chorea were
      also assessed with the Universidade Federal de Minas Gerais Sydenham Chorea
      Rating Scale. RESULTS: Performance in verbal fluency and in verbal comprehension
      tasks differed significantly (P < 0.01) among the three groups. Patients with
      Sydenham chorea performed significantly worse than healthy control group in
      phonemic and semantic verbal fluency tasks as well as in the Token Test. The
      group with rheumatic fever also performed worse than healthy controls in phonemic
      verbal fluency. Severity of motor signs in Sydenham chorea inversely correlated
      with performance in phonemic verbal fluency (words beginning with letter S, and
      total sum of words beginning with letters F, A, and S). CONCLUSIONS: Adolescents
      with Sydenham chorea show difficulties in verbal fluency and in verbal
      comprehension. Patients with rheumatic fever also have some degree of language
      impairment. Future studies must investigate language impairment in difference
      stages of Sydenham chorea (acute, persistent, and remission) and putative
      biological markers.

PMID- 26296450
TI  - Prevalence of malaria infection in pregnant women compared with children for
      tracking malaria transmission in sub-Saharan Africa: a systematic review and meta
      analysis.
AB  - BACKGROUND: In malarious areas, pregnant women are more likely to have detectable
      malaria than are their non-pregnant peers, and the excess risk of infection
      varies with gravidity. Pregnant women attending antenatal clinic for their first
      visit are a potential pragmatic sentinel group to track the intensity of malaria
      transmission; however, the relation between malaria prevalence in children, a
      standard measure to estimate malaria endemicity, and pregnant women has never
      been compared. METHODS: We obtained data on malaria prevalence in pregnancy from
      the Malaria in Pregnancy Library (January, 2015) and data for children (0-59
      months) were obtained from recently published work on parasite prevalence in
      Africa and the Malaria in Pregnancy Library. We used random effects meta-analysis
      to obtain a pooled prevalence ratio (PPR) of malaria in children versus pregnant
      women (during pregnancy, not at delivery) and by gravidity, and we used meta
      regression to assess factors affecting the prevalence ratio. FINDINGS: We used
      data from 18 sources that included 57 data points. There was a strong linear
      relation between the prevalence of malaria infection in pregnant women and
      children (r=0.87, p<0.0001). Prevalence was higher in children when compared with
      all gravidae (PPR=1.44, 95% CI 1.29-1.62; I(2)=80%, 57 studies), and against
      multigravidae (1.94, 1.68-2.24; I(2)=80%, 7 studies), and marginally higher
      against primigravidae (1.16, 1.05-1.29; I(2)=48%, 8 studies). PPR was higher in
      areas of higher transmission. INTERPRETATION: Malaria prevalence in pregnant
      women is strongly correlated with prevalence data in children obtained from
      household surveys, and could provide a pragmatic adjunct to survey strategies to
      track trends in malaria transmission in Africa. FUNDING: The Malaria in Pregnancy
      Consortium, which is funded through a grant from the Bill & Melinda Gates
      Foundation to the Liverpool School of Tropical Medicine, UK; US Centers for
      Disease Control and Prevention; and Wellcome Trust, UK.

PMID- 26296452
TI  - A randomized trial comparing the effect of weight loss and exercise training on
      insulin sensitivity and glucose metabolism in coronary artery disease.
AB  - AIM: The majority of patients with coronary artery disease (CAD) exhibit abnormal
      glucose metabolism, which is associated with mortality even at non-diabetic
      glucose levels. This trial aims to compare the effects of a considerable weight
      loss and exercise with limited weight loss on glucose metabolism in prediabetic,
      CAD patients. METHODS AND RESULTS: Seventy non-diabetic participants with CAD,
      BMI 28-40 kg/m(2), age 45-75 years were randomized to 12 weeks' aerobic interval
      training (AIT) at 90% peak heart rate three times weekly or a low energy diet
      (LED, 800-1,000 kcal/day) for 8-10 weeks followed by 2-4 weeks' weight
      maintenance diet. Glucose tolerance, insulin action, beta-cell function and
      suppression of lipolysis were assessed using a 3-h oral glucose tolerance test.
      ISI-composite and ISI-HOMA (=1/HOMA-IR) were calculated as surrogate measures of
      whole-body and hepatic insulin sensitivity, respectively. Magnetic resonance
      imaging estimated abdominal adipose tissue. Twenty-six (74%) AIT and 29 (83%) LED
      participants completed intervention per protocol. LED increased ISI-composite by
      55% and ISI-HOMA by 70% (p<0.01) while AIT did not change insulin sensitivity
      (p>0.7) revealing a significant difference between the groups (p<0.05). No
      concurrent significant changes in lipolysis, beta-cell responsiveness or insulin
      clearance were seen. Changes in ISI-HOMA and ISI-composite were associated with
      reduced visceral abdominal fat, waist circumference and body weight. Intention-to
      treat analyses (n=64) yielded similar results. CONCLUSION: LED is superior to AIT
      in improving insulin sensitivity in prediabetic CAD patients. Changes in insulin
      sensitivity are associated with decreased visceral abdominal fat, waist
      circumference and body weight.

PMID- 26296453
TI  - Smoke, pheromone and kairomone olfactory receptor neurons in males and females of
      the pine sawyer Monochamus galloprovincialis (Olivier) (Coleoptera:
      Cerambycidae).
AB  - The response of antennal olfactory receptor neurons (ORNs) of Monochamus
      galloprovincialis to several odourants was tested using single sensillum
      electrophysiology. Behaviourally active pheromone, and kairomone (host and
      sympatric bark beetle pheromone) odours were tested alongside smoke compounds
      released by burnt wood that are potentially attractive to the insect. The
      antennae bore several types of sensilla. Two plate areas in the proximal and
      distal ends of each antennal segment were covered with basiconic sensilla that
      responded to the odour stimuli. Sensilla basiconica contained one or two cells of
      different spike amplitude. The 32 male and 38 female ORNs tested responded with
      excitations or inhibitions to the different plant odours. In general the response
      of male and female receptors was very similar so they were pooled to perform a
      cluster analysis on ORN responses. Six ORNs were clearly specialised for
      pheromone reception. Responses to kairomone and smoke odours were less specific
      than those of pheromone, but a group of 9 cells was clearly excited by smoke
      compounds (mainly eugenol and 4-methyl 2-methoxyphenol), a group of 8 cells was
      very responsive to alpha-pinene, beta-pinene and cis-verbenol, and a group of 14
      cells responded to a wider range of compounds. The rest of the cells (47%) were
      either non-responsive or slightly inhibited by smoke compounds. Dose-response
      curves were obtained for several compounds. Different compounds induced
      significantly different latencies and these appeared to be unrelated to their
      boiling point. 

PMID- 26296454
TI  - The utility of chest X-ray as a screening tool for blunt thoracic aortic injury.
AB  - BACKGROUND: The early and accurate identification of patients with blunt thoracic
      aortic injury (BTAI) remains a challenge. Traditionally, a portable AP chest X
      ray (CXR) is utilized as the initial screening modality for BTAI, however, there
      is controversy surrounding its sensitivity. The purpose of this study was to
      assess the sensitivity of CXR as a screening modality for BTAI. METHODS: After
      IRB approval, all adult (>=18 yo) blunt trauma patients admitted to LAC+USC
      (01/2011-12/2013) who underwent CXR and chest CT were retrospectively reviewed.
      Final radiology attending CXR readings were reviewed for mediastinal
      abnormalities (widened mediastinum, mediastinal to chest width ratio greater than
      0.25, irregular aortic arch, blurred aortic contour, opacification of the
      aortopulmonary window, and apical pleural haematoma) suggestive of aortic injury.
      Chest CT final attending radiologist readings were utilized as the gold standard
      for diagnosis of BTAI. The primary outcome analyzed was CXR sensitivity. RESULTS:
      A total of 3728 patients were included in the study. The majority of patients
      were male (72.6%); mean age was 43 (SD 20). Median ISS was 9 (IQR 4-17) and
      median GCS was 15 (IQR 14-15). The most common mechanism of injury was MVC
      (48.0%), followed by fall (20.6%), and AVP (16.9%). The total number of CXRs
      demonstrating a mediastinal abnormality was 200 (5.4%). Widened mediastinum was
      present on 191 (5.1%) of CXRs, blurred aortic contour on 10 (0.3%), and irregular
      aortic arch on 4 (0.1%). An acute aortic injury confirmed by chest CT was present
      in 17 (0.5%) patients. Only 7 of these with CT-confirmed BTAI had a mediastinal
      abnormality identified on CXR, for a sensitivity of 41% (95% CI: 19-67%).
      CONCLUSION: The results from this study suggest that CXR alone is not a reliable
      screening modality for BTAI. A combination of screening CXR and careful
      consideration of other factors, such as mechanism of injury, will be required to
      effectively discriminate between those who should and should not undergo chest
      CT.

PMID- 26296455
TI  - Trends in incidence rate, health care consumption, and costs for patients
      admitted with a humeral fracture in The Netherlands between 1986 and 2012.
AB  - INTRODUCTION: This study aimed to examine long-term population-based trends in
      the incidence rate of patients with a humeral fracture admitted to a hospital in
      the Netherlands from 1986 to 2012 and to give a detailed overview of the health
      care consumption and productivity loss with associated costs. MATERIALS AND
      METHODS: Age and gender-standardised incidence rates of hospital admissions for
      patients with a proximal, shaft, or distal humeral fracture were calculated for
      each year (1986-2012). Injury cases, length of hospital stay (LOS), trauma
      mechanism, and operation rate were extracted from the National Medical
      Registration. An incidence-based cost model was applied to calculate costs for
      direct health care and lost productivity in 2012. RESULTS: Between 1986 and 2012
      112,910 patients were admitted for a humeral fracture. The incidence rate
      increased from 17.8 in 1986 to 40.0 per 100,000 person years in 2012. Incidence
      rates of proximal fractures increased the most, especially in elderly women.
      Operation rates decreased in patients aged 70 years or older. The mean LOS
      decreased from nine days in 1997 to five days in 2012. The cumulative LOS of all
      patients in 2012 was 28,880 days of which 73% were caused by women and 81% were
      caused by patients aged 50 years or older. Cumulative medical costs in 2012 were
      M?55.4, of which M?43.4 was spent on women. Costs increased with age. Costs for
      hospital care contributed most to the overall costs per case until 70 years of
      age. From 70 years onwards, the main cost determinants were hospital care,
      rehabilitation/nursing care, and home care. Cumulative costs due to lost
      productivity were M?23.5 in 2012. Costs per case increased with age in all
      anatomic regions. CONCLUSIONS: The crude number of patients admitted for a
      humeral fracture increased 124% in 27 years, and was associated with age and
      gender. Proximal fractures in elderly women accounted most significantly for this
      increase and most of the costs. The main cost determinants were hospital care and
      productivity loss.

PMID- 26296456
TI  - Clinical indications of computed tomography (CT) of the head in patients with low
      energy geriatric hip fractures.
AB  - OBJECTIVE: To define the role of head computed tomography (CT) scans in the
      geriatric population with isolated low-energy femur fractures and describe the
      pertinent clinical variables which are associated with positive CT findings with
      the objective to decrease the number of unnecessary CT scans performed. DESIGN:
      Retrospective review. SETTING: Level I trauma centre. PATIENTS: Eleven hundred
      ninety-two (1192) patients sustaining a femur fracture following a low-energy
      fall. MAIN OUTCOME MEASUREMENT: Pertinent clinical variables that were associated
      with CTs that yielded positive findings. RESULTS: Two hundred fifty patients
      (21%) underwent a head CT scan as part of their evaluation. Of these patients,
      83% suffered proximal femur fractures, 11% shaft fractures and 6% distal
      fractures. The majority of the patients were evaluated by the emergency
      department (ED) with only 18% (44/250) being evaluated by the trauma team.
      Average patient age was 83 years (range 65-99 years). One hundred seventy-three
      patients (69%) were on some form of antiplatelet medication or anticoagulation.
      Of the 250 patients who underwent head CT scan, 16 (6%) patients had acute
      findings (haemorrhage - 15, infarct - 1), and none of the patients required
      neurosurgical intervention. CONCLUSION: None of the patients with a traumatic
      injury required a neurosurgical invention after sustaining a low energy fall
      (0/1192). Head CT scans should have a limited role in the work-up of this patient
      population and should be reserved for patients with a history and physical
      findings that support head trauma. LEVEL OF EVIDENCE: Prognostic level III. See
      instructions for authors for a complete description of levels of evidence.

PMID- 26296457
TI  - Resequencing diverse Chinese indigenous breeds to enrich the map of genomic
      variations in swine.
AB  - To enrich the map of genomic variations in swine, we randomly sequenced 13
      domestic and wild individuals from China and Europe. We detected approximately
      28.1 million single nucleotide variants (SNVs) and 3.6 million short insertions
      and deletions (INDELs), of which 2,530,248 SNVs and 3,456,626 INDELs were firstly
      identified compared with dbSNP 143. Moreover, 208,687 SNVs and 24,161 INDELs were
      uniquely observed in Chinese pigs, potentially accounting for phenotypic
      differences between Chinese and European pigs. Furthermore, significantly high
      correlation between SNV and INDEL was witnessed, which indicated that these two
      distinct variants may share similar etiologies. We also predicted loss of
      function genes and found that they were under weaker evolutionary constraints.
      This study gives interesting insights into the genomic features of the Chinese
      pig breeds. These data would be useful in the establishment of high-density SNP
      map and would lay a foundation for facilitating pig functional genomics study. 

PMID- 26296458
TI  - Mesenchymal stem cells for the treatment of neurological diseases:
      Immunoregulation beyond neuroprotection.
AB  - An inflammatory response is often observed in neurological diseases, being
      characterized sometimes by activation of adaptive cells (T and B lymphocytes)
      and, almost inexorably, of cells of the innate immunity (microglial cells,
      macrophages). Mesenchymal stromal/stem cells represent a promising therapeutic
      approach for the treatment of intractable neurological diseases given the
      possibility that they affect neurodegeneration both directly and indirectly,
      through their potent immunomodulatory effect. Here we will review the evidence,
      mostly deriving from preclinical studies, that MSC, beyond their ability to
      foster neurorepair, can ameliorate neurodegenerative diseases through their
      effect on associated immune responses. 

PMID- 26296459
TI  - Increasing DNA reactivity and in vitro antitumor activity of trans diiodido
      Pt(II) complexes with UVA light.
AB  - Trans diiodido platinum(II) complexes bearing the same as well as different
      aliphatic amines (mixed-amines) have interesting biological activity;
      cytotoxicity and interactions with some important biological models have already
      been demonstrated. Herein we described the interaction of such compounds with ct
      DNA, supercoiled and linearized plasmid DNA and 5-GMP. Interestingly, UV
      irradiation of these compounds results in an increase in reactivity towards DNA
      and 5-GMP in such model systems. Additionally, the cytotoxicity of the trans
      Pt(II) complexes towards human cancer cells is noticeably increased when
      treatment is combined for 90min with UVA-irradiation. With this work we provide
      evidence that trans diiodido compounds can be activated by UV-light over
      relatively short treatment times. 

PMID- 26296460
TI  - Human glutaredoxin 3 can bind and effectively transfer [4Fe-4S] cluster to apo
      iron regulatory protein 1.
AB  - Glutaredoxin 3 (GLRX3) is a member of monothiol glutaredoxins with a CGFS active
      site that has been demonstrated to function in cellular iron sensing and
      trafficking via its bound iron-sulfur cluster. Human GLRX3 has been shown to form
      a dimer that binds two bridging [2Fe-2S] clusters with glutathione (GSH) as a
      ligand, assembling a compound 2GLRX3-2[2Fe-2S]-4GSH. Each iron of the iron-sulfur
      clusters is bound to the thiols of the cysteines, one of which is from the active
      site of GLRX3, the other from the noncovalently bound GSH. Here, we show that the
      recombinant human GLRX3 isolated anaerobically from Escherichia coli can
      incorporate [4Fe-4S] cluster in the absence of GSH, revealed by spectral and
      enzymatic analysis. [4Fe-4S] cluster-containing GLRX3 is competent for converting
      iron regulatory protein 1 (apo-IRP1) into aconitase within 30 min, via intact
      iron-sulfur cluster transfer. These in vitro studies suggest that human GLRX3 is
      important for cytosolic Fe-S protein maturation.

PMID- 26296461
TI  - Analysis of the subcellular localization of the human histone methyltransferase
      SETDB1.
AB  - SET domain, bifurcated 1 (SETDB1) is a histone methyltransferase that methylates
      lysine 9 on histone H3. Although it is important to know the localization of
      proteins to elucidate their physiological function, little is known of the
      subcellular localization of human SETDB1. In the present study, to investigate
      the subcellular localization of hSETDB1, we established a human cell line
      constitutively expressing enhanced green fluorescent protein fused to hSETDB1. We
      then generated a monoclonal antibody against the hSETDB1 protein. Expression of
      both exogenous and endogenous hSETDB1 was observed mainly in the cytoplasm of
      various human cell lines. Combined treatment with the nuclear export inhibitor
      leptomycin B and the proteasome inhibitor MG132 led to the accumulation of
      hSETDB1 in the nucleus. These findings suggest that hSETDB1, localized in the
      nucleus, might undergo degradation by the proteasome and be exported to the
      cytosol, resulting in its detection mainly in the cytosol. 

PMID- 26296462
TI  - ANGUSTIFOLIA mediates one of the multiple SCRAMBLED signaling pathways regulating
      cell growth pattern in Arabidopsis thaliana.
AB  - In Arabidopsis thaliana, an atypical leucine-rich repeat receptor-like kinase,
      SCRAMBLED (SCM), is required for multiple developmental processes including root
      epidermal cell fate determination, silique dehiscence, inflorescence growth,
      ovule morphogenesis, and tissue morphology. Previous work suggested that SCM
      regulates these multiple pathways using distinct mechanisms via interactions with
      specific downstream factors. ANGUSTIFOLIA (AN) is known to regulate cell and
      tissue morphogenesis by influencing cortical microtubule arrangement, and
      recently, the AN protein was reported to interact with the SCM protein.
      Therefore, we examined whether AN might be responsible for mediating some of the
      SCM-dependent phenotypes. We discovered that both scm and an mutant lines cause
      an abnormal spiral or twisting growth of roots, but only the scm mutant affected
      root epidermal patterning. The siliques of the an and scm mutants also exhibited
      spiral growth, as previously reported, but only the scm mutant altered silique
      dehiscence. Interestingly, we discovered that the spiral growth of roots and
      siliques of the scm mutant is rescued by a truncated SCM protein that lacks its
      kinase domain, and that a juxtamembrane domain of SCM was sufficient for AN
      binding in the yeast two-hybrid analysis. These results suggest that the AN
      protein is one of the critical downstream factors of SCM pathways specifically
      responsible for mediating its effects on cell/tissue morphogenesis through
      cortical microtubule arrangement. 

PMID- 26296463
TI  - Role of melatonin, melatonin receptors and STAT3 in the cardioprotective effect
      of chronic and moderate consumption of red wine.
AB  - We have recently discovered that melatonin, given acutely and directly to the
      isolated heart at the concentration found in wine, confers cardioprotection
      against ischemia-reperfusion (I/R). However, whether the presence of melatonin in
      wine contributes to the cardioprotective effect of chronic and moderate
      consumption of wine and its signalling mechanisms of protection are unknown. We
      therefore used both in vivo and in vitro models of I/R to investigate whether the
      presence of melatonin in red wine may contribute to the cardioprotective effect
      of chronic and moderate consumption of red wine. Wistar rats and C57black6 mice
      (WT) received drinking water supplemented daily with a moderate amount of red
      wine or melatonin given at the concentration found in the red wine. Rats were
      also pretreated with luzindole, a specific inhibitor of melatonin receptors 1 and
      2 (2.3 mg/kg/day, intraperitoneally) or prazosin, a specific inhibitor of
      melatonin receptor type 3 (2.5 mg/kg/day, intraperitoneally). After 14 days,
      hearts were subjected to I/R in vivo or ex vivo. Red wine reduced the infarct
      size in both rats and WT mice (p < 0.001). Luzindole did not affect wine-induced
      cardioprotection, while prazosin reduced the infarct sparing effect of red wine
      (p < 0.05). Furthermore, red wine or melatonin failed to protect tumor necrosis
      factor alpha (TNF) receptor 2 knockout or cardiomyocyte specific signal
      transducer and activator of transcription 3 (STAT3) deficient mice (n.s. vs.
      control). Our novel findings suggest that the presence of melatonin in red wine
      contributes to the cardioprotective effect of chronic and moderate consumption of
      red wine against lethal I/R injuries. This effect is most likely mediated, at
      least in part, via melatonin receptor 3 and the activation of TNF and STAT3, both
      key players of the prosurvival and well described SAFE pathway.

PMID- 26296464
TI  - Sulforaphane induces apoptosis in adipocytes via Akt/p70s6k1/Bad inhibition and
      ERK activation.
AB  - Sulforaphane (SFN), an isothiocyanate isolated from cruciferous vegetables,
      possesses anti-oxidant and anti-cancer bioactivities. Moreover, SFN exerts its
      pro-apoptotic effects in some cancer lines. However, the effects and mechanisms
      of SFN on the regulation of apoptosis of adipocytes are still unknown. In this
      study, we found that SFN induced significant apoptosis in 3T3-L1 adipocytes and
      markedly decreased the cellular lipid content. Western blot demonstrated that SFN
      induced apoptosis was mediated via the mitochondrial apoptosis pathway based on
      increased cleavage of poly-ADP-ribose-polymerase (PARP), release of cytochrome c
      into the cytoplasm, and activation of caspase-3, as well as decreased Bcl-2/Bax
      ratio. In addition, SFN markedly decreased phosphorylation of Akt and downstream
      proteins, p70s6k1 and Bad, and increased phosphorylation of ERK. Therefore, our
      findings clarified that SFN could induce 3T3-L1 adipocyte apoptosis via down
      regulation of the Akt/p70s6k1/Bad pathway and up-regulation of the ERK pathway,
      suggesting SFN may be a promising agent for the treatment or prevention of
      obesity. 

PMID- 26296465
TI  - Identification and characterization of a dipeptidyl peptidase IV inhibitor from
      aronia juice.
AB  - Aronia berries have many potential effects on health, including an antioxidant
      effect, effect for antimutagenesis, hepatoprotection and cardioprotection, an
      antidiabetic effect and inhibition of cancer cell proliferation. Previous human
      studies have shown that aronia juice may be useful for treatment of obesity
      disorders. In this study, we found that aronia juice has an inhibitory effect
      against dipeptidyl peptidase IV (DPP IV) (EC 3.4.14.5). DPP IV is a peptidase
      that cleaves the N-terminal region of incretins such as glucagon-dependent
      insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1).
      Inactivation of incretins by DPP IV induces reduction of insulin secretion.
      Furthermore, we identified that cyanidin 3, 5-diglucoside as the DPP IV inhibitor
      in aronia juice. DPP IV was inhibited more strongly by cyanidin 3, 5-diglucoside
      than by cyanidin and cyanidin 3-glucoside. The results suggest that DPP IV is
      inhibited by cyanidin 3, 5-diglucoside present in aronia juice. The antidiabetic
      effect of aronia juice may be mediated through DPP IV inhibition by cyanidin 3, 5
      diglucoside. 

PMID- 26296466
TI  - The Sirt1 activator SRT1720 attenuates angiotensin II-induced atherosclerosis in
      apoE-/- mice through inhibiting vascular inflammatory response.
AB  - Activation of the silent mating type information regulation 2 homolog 1 (SIRT1)
      has been shown consistent antiinflammatory function. However, little information
      is available on the function of SIRT1 during Angiotensin II (AngII)-induced
      atherosclerosis. Here we report atheroprotective effects of sirt1 activation in a
      model of AngII-accelerated atherosclerosis, characterized by suppression pro
      inflammatory transcription factors Nuclear transcription factor (NF)-kappaB and
      Signal Transducers and Activators of Transcription. (STAT) signaling pathway, and
      atherosclerotic lesion macrophage content. In this model, administration of the
      SIRT1 agonist SRT1720 substantially attenuated AngII-accelerated atherosclerosis
      with decreasing blood pressure and inhibited NF-kappaB and STAT3 activation,
      which was associated with suppression of inflammatory factor and atherogenic gene
      expression in the artery. In vitro studies demonstrated similar changes in AngII
      treated VSMCs and macrophages: SIRT1 activation inhibited the expression levels
      of proinflammatory factor. These studies uncover crucial proinflammatory
      mechanisms of AngII and highlight actions of SIRT1 activation to inhibit AngII
      signaling, which is atheroprotective.

PMID- 26296467
TI  - Fentanyl inhibits the invasion and migration of colorectal cancer cells via
      inhibiting the negative regulation of Ets-1 on BANCR.
AB  - BACKGROUND: Recent studies have shown the potential anti-tumor effect of fentanyl
      on colorectal cancer (CRC). However, its underling mechanism is still unclear.
      Since studies indicates the abnormal expression of transcription factor Ets-1 and
      BRAF-activated lncRNA (BANCR) in CRC progress, the relationship between Ets-1 and
      BANCR was investigated here to illustrate the fentanyl-induced mechanism on CRC
      in vitro. METHODS: The expression levels of Ets-1 and BANCR were first detected
      in fentanyl-treated CRC cells. The interaction between Ets-1 and BANCR promoter
      was verified with chromatin immunoprecipitation assays, as well as corresponding
      acetylation of histones. The regulation of Ets-1 on BANCR expression was
      confirmed through luciferase assays and RT-PCR analysis. And, cell clone
      formation, cell migration and invasion were observed to evaluate the anti-tumor
      effects of fentanyl. Ets-1 overexpression or co-overexpression with BANCR was
      further performed by plasmids transfection to show the regulatory role of Ets-1
      in fentanyl-induced mechanism. RESULTS: Fentanyl induced BANCR upregulation and
      Ets-1 downregulation in CRC cells. Further studies showed that Ets-1 negatively
      regulated BANCR expression via the deacetylation of histones H3 within BANCR
      promoter. Moreover, fentanyl induced less cell clone formation, as well as
      inhibited cell migration and invasion in vitro, while Ets-1 overexpression
      inhibited fentanyl-induced effects that could be reversed by BANCR co
      overexpression. CONCLUSION: Fentanyl showed anti-tumor like effects on CRC cells,
      including less cell clone formation and inhibited cell migration and invasion.
      Furthermore, the regulatory role of Ets-1 on BANCR influenced fentanyl-induced
      mechanism, indicating their potential application in the therapeutic treatment of
      CRC.

PMID- 26296468
TI  - PI3K is involved in P2Y receptor-regulated cAMP /Epac/Kv channel signaling
      pathway in pancreatic beta cells.
AB  - P2Y receptors (P2YR) are a family of purinergic G protein-coupled receptors,
      which could be stimulated by extracellular nucleotides. In pancreatic beta cells,
      activation of P2YR has long been shown to stimulate insulin secretion in a
      glucose-dependent manner. Previously, we reported that P2YR-modulated insulin
      secretion is mediated by a cAMP/Epac/Kv channel pathway. However, the interaction
      between Epac and the Kv channel in P2YR-modulated insulin secretion remains
      unclear. In this study, we used patch-clamp technique and insulin secretion assay
      to investigate the potential molecules that may link Epac to Kv channel
      inhibition induced by P2YR activation. We identified that phosphatidylinositide 3
      kinase, which mediates P2YR-regulated insulin secretion, is a critical mediator
      between Epac and the Kv channel. 

PMID- 26296469
TI  - GATA-1 directly regulates Nanog in mouse embryonic stem cells.
AB  - Nanog safeguards pluripotency in mouse embryonic stem cells (mESCs). Insight into
      the regulation of Nanog is important for a better understanding of the molecular
      mechanisms that control pluripotency of mESCs. In a silico analysis, we identify
      four GATA-1 putative binding sites in Nanog proximal promoter. The Nanog promoter
      activity can be significantly repressed by ectopic expression of GATA-1 evidenced
      by a promoter reporter assay. Mutation studies reveal that one of the four
      putative binding sites counts for GATA-1 repressing Nanog promoter activity.
      Direct binding of GATA-1 on Nanog proximal promoter is confirmed by
      electrophoretic mobility shift assay and chromatin immunoprecipitation. Our data
      provide new insights into the expanded regulatory circuitry that coordinates
      Nanog expression. 

PMID- 26296470
TI  - Caffeic acid phenethyl ester inhibits 3-MC-induced CYP1A1 expression through
      induction of hypoxia-inducible factor-1alpha.
AB  - Caffeic acid phenethyl ester (CAPE), a natural component of propolis, is reported
      to have anticarcinogenic properties, although its precise chemopreventive
      mechanism remains unclear. In this study, we examined the effects of CAPE on 3
      methylcholanthrene (3-MC)-induced CYP1A1 expression and activities. CAPE reduced
      the formation of the benzo[a]pyrene-DNA adduct. Moreover, CAPE inhibited 3-MC
      induced CYP1A1 activity, mRNA expression, protein level, and promoter activity.
      CAPE treatment also decreased 3-MC-inducible xenobiotic-response element (XRE)
      linked luciferase, aryl hydrocarbons receptor (AhR) transactivation and nuclear
      localization. CAPE induced hypoxia inducible factor-1alpha (HIF-1alpha) protein
      level and HIF-1alpha responsible element (HRE) transcriptional activity. CAPE
      mediated HIF-1alpha reduced 3-MC-inducible CYP1A1 protein expression. Taken
      together, CAPE decreases 3-MC-mediated CYP1A1 expression, and this inhibitory
      response is associated with inhibition of AhR and HIF-1alpha induction. 

PMID- 26296471
TI  - Non-traumatic subdural hematoma secondary to septic brain embolism: A rare cause
      of unexpected death in a drug addict suffering from undiagnosed bacterial
      endocarditis.
AB  - Acute subdural hematomas are mostly due to blunt traumatization of the head. In
      rare instances, subdural bleeding occurs without evidence of a previous trauma
      following spontaneous hemorrhage, e.g. from a ruptured aneurysm or an
      intracerebral hematoma perforating the brain surface and the arachnoid. The paper
      presents the morphological, microbiological and toxicological findings in a 38
      year-old drug addict who was found by his partner in a dazed state. When brought
      to a hospital, he underwent trepanation to empty a right-sided subdural hematoma,
      but he died already 4h after admission. Autopsy revealed previously undiagnosed
      infective endocarditis of the aortic valve as well as multiple infarctions of
      brain, spleen and kidneys obviously caused by septic emboli. The subdural
      hematoma originated from a subcortical brain hemorrhage which had perforated into
      the subdural space. Microbiological investigation of the polypous vegetations
      adhering to the aortic valve revealed colonization by Streptococcus mitis and
      Klebsiella oxytoca. According to the toxicological analysis, no psychotropic
      substances had contributed to the lethal outcome. The case reported underlines
      that all deaths of drug addicts should be subjected to complete forensic autopsy,
      as apart from intoxications also natural and traumatic causes of death have to be
      taken into consideration. 

PMID- 26296472
TI  - Mutations of desmoglein-2 in sudden death from arrhythmogenic right ventricular
      cardiomyopathy and sudden unexplained death.
AB  - Desmoglein-2 (DSG2), a member of the desmosomal cadherin superfamily, has been
      linked to arrhythmogenic right ventricular cardiomyopathy (ARVC)which may cause
      life-threatening ventricular arrhythmias and sudden death. Fatal arrhythmias
      resulting in sudden death also occur in the absence of morphologic cardiac
      abnormalities at autopsy. We sequenced all 15 exons of DSG2 in DNA extracted from
      post-mortem heart tissues of 25 patients dying with ARVC and 25 from sudden
      unexplained death (SUD). The primers were designed using the Primer Express 3.0
      software. Direct sequencing for both sense and antisense strands was performed
      with a BigDye Terminator DNA sequencing kit on a 3130 xl Genetic Analyzer.
      Mutation damage prediction was made using Mutation Taster, Polyphen and SIFT
      software. 2 DSG2 mutations (p. S1026Q fsX12, p. G678R)in two ARVC samples and 2
      DSG2 mutations(p. E 896K, p. A858 V) in two SUD samples were identified, all the
      mutations were novel. We concluded that DSG2 mutations may not specific for ARVC
      and may be related to the fatal arrhythmic events even in patients with a
      morphological normal heart. 

PMID- 26296474
TI  - A protein domain-based view of the virosphere-host relationship.
AB  - Despite being an important and inseparable part of the biosphere, viruses are too
      often overlooked in several life sciences, including evolutionary biology,
      systems biology, and non-marine ecology. In this review, a protein domain-based
      view of viral proteomes, the proteomes of other organisms and the overlap between
      them is presented. The data show that in many viral species, viral proteins are
      not very well annotated with protein domains. Compared with viral proteomes,
      cellular proteomes are covered quite uniformly with respect to protein domains
      and show higher coverage. A tremendous number of virally coded domains exist; in
      fact, the number of protein domains in the characterised virosphere is
      approaching that found in Archaea, a well-accepted superkingdom. Proteins encoded
      by viruses contain virosphere-specific domains (i.e., not found in cellular
      proteomes) and/or many domains shared by viral and cellular proteomes. Virosphere
      specific domains are structurally peculiar with respect to different structural
      measures, making them a clear source of structural and functional novelty. Viral
      families with RNA genomes tend to harbour more virosphere-specific domains than
      other viruses. Interestingly, host range preferences of different viral classes
      are, for the most part, not reflected by domains shared between viruses and
      different superkingdoms. The role of viruses in the genesis of the cellular
      domain repertoire is reviewed to bring them more confidently and firmly into the
      larger biological picture. 

PMID- 26296473
TI  - Cross-reactivity of anti-PLA2R1 autoantibodies to rabbit and mouse PLA2R1
      antigens and development of two novel ELISAs with different diagnostic
      performances in idiopathic membranous nephropathy.
AB  - About 70% of patients with idiopathic membranous nephropathy (iMN) have
      autoantibodies to the phospholipase A2 receptor PLA2R1. We screened sera from iMN
      patients for their cross-reactivity to human (h), rabbit (rb) and mouse (m)
      PLA2R1 by western blot (WB) and antigen-specific ELISAs. All iMN patients
      recognized hPLA2R1 and rbPLA2R1 by WB, and a rbPLA2R1 ELISA was as sensitive as
      the standardized hPLA2R1 ELISA to monitor anti-PLA2R1 in patients with active
      disease or in drug-induced remission. In contrast, only 51% of patients were
      reactive to mPLA2R1 by WB, and a maximum of 78% were weakly to highly positive in
      the mPLA2R1 ELISA, suggesting that iMN patients exhibit different subsets of anti
      PLA2R1 autoantibodies against epitopes that are shared or not among PLA2R1
      orthologs. In a cohort of 41 patients with a mean follow-up of 42 months from
      anti-PLA2R1 assay, the detection of anti-mPLA2R1 autoantibodies was an
      independent predictor of clinical outcome in multivariate analysis (p = 0.009),
      and a ROC curve analysis identified a threshold of 605 RU/mL above which 100% of
      patients (12 patients) had a poor renal outcome (p < 0.001). A similar threshold
      could not be defined in hPLA2R1 and rbPLA2R1 ELISAs. We conclude that rbPLA2R1 is
      an alternative antigen to hPLA2R1 to measure anti-PLA2R1 in active disease while
      mPLA2R1 is a unique antigen that can detect a subset of anti-PLA2R1
      autoantibodies present at high levels (>605 RU/mL) only in iMN patients at risk
      of poor prognosis, and is thus useful to predict iMN outcome. 

PMID- 26296475
TI  - Synthesis of BF3 catalyzed Mannich derivatives with excellent ee from
      phenylpropanolamine, study of their antimicrobial activity and molecular docking.
AB  - Antimicrobial agents 4a-g and 5a-g with very good potency were synthesized with
      100% ee from phenylpropanolamine (norephedrine) by BF3 catalyzed three components
      one pot Mannich reaction in good yields. Obtained compounds were characterized
      using spectral techniques. Antimicrobial study of these compounds revealed a good
      to very high potential activity against tested microbes when compared to standard
      antimicrobial drugs streptomycin and ketoconazole. These synthesized compounds
      exhibited significant minimum inhibitory concentration (MIC) values against Gram
      positive and Gram negative bacteria. Amongst compound 4b, 4c, 4d, 4e, 5a, and 5e
      exhibited very high potent MIC values against tested twelve bacteria and three
      fungi when compared to control. When subjected to molecular docking, in silico
      studies revealed significant binding energies ranging from -7.06 to -8.90
      kcal/mol for all obtained compounds towards target receptor DNA topoisomerase IV
      and amongst compounds 4b and 4d have shown maximum binding energies 8.70 and 8.90
      kcal/mol, respectively.

PMID- 26296476
TI  - A novel sesquiterpene and three new phenolic compounds from the rhizomes of
      Acorus tatarinowii Schott.
AB  - A novel sesquiterpene with an unprecedented epoxy lactone skeleton, named
      tatarinolactone, together with two new amides, a new biphenylpropanoid and two
      known lignans were isolated from the rhizomes of Acorus tatarinowii Schott. Their
      structures were identified as 6,7,8-trihydroxy-4alpha-isobutyl-4,7
      dimethylhexahydro-6,8alpha-epoxychromen-2(3H)-one (1), (E)-methyl 4-[3-(4-hydroxy
      3-methoxyphenyl)acrylamido]butanoate (2), (Z)-methyl 4-[3-(4-hydroxy-3
      methoxyphenyl)acrylamido]butanoate enol isomer (3), (R)-4-hydroxy-3-[1-hydroxy-3
      (4-hydroxy-3-methoxyphenyl)propan-2-yl]-5-methoxybenzoic acid (4), (2S,3R)
      ceplignan (5), and (2R,3S)-ceplignan (6), respectively, based on extensive
      spectroscopic analysis and by comparison to the known compounds. To test their
      effects on serotonin transporters, a high content assay using hSERT-HEK293 cell
      line was adopted. Results indicated that compounds 1 and 4 significantly
      inhibited SERT activity, while compounds 2, 3, 5, and 6 significantly enhanced
      SERT activity, which partly explain the traditional uses of the rhizomes of
      Acorus tatarinowii Schott in treatments of neuropsychiatric and digestive
      disorders.

PMID- 26296478
TI  - Differential influence of 7 cations on 16 non-competitive NMDA receptor blockers.
AB  - The specific binding of the NMDA receptor (NR) channel ligand [(3)H]MK-801 to rat
      brain membranes is sensitive to positively charged buffer ingredients as to
      tris(hydroxymethyl)aminomethane (Tris), to Na(+), or to protons. Here we
      demonstrate that 16 non-competitive NR antagonists, including 5 long-chain
      diamines, classical NR channel blockers and several less known compounds, differ
      widely in their sensitivities to cationic buffer constituents. Although
      chemically distinguished either as extended di-cationic or as compact mono
      cationic, their sensitivities to cationic buffer ingredients did not suggest this
      grouping. While the di-cationic compounds are known for their sensitivity to
      spermine (polyamine inverse agonists), also some of the mono-cationic blockers
      exhibited this feature. They might share as common target a recently described
      negatively charged extracellular GluN1/GluN2B interface.

PMID- 26296477
TI  - 7-(Pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine-based derivatives for kinase
      inhibition: Co-crystallisation studies with Aurora-A reveal distinct differences
      in the orientation of the pyrazole N1-substituent.
AB  - Introduction of a 1-benzyl-1H-pyrazol-4-yl moiety at C7 of the imidazo[4,5
      b]pyridine scaffold provided 7a which inhibited a range of kinases including
      Aurora-A. Modification of the benzyl group in 7a, and subsequent co
      crystallisation of the resulting analogues with Aurora-A indicated distinct
      differences in binding mode dependent upon the pyrazole N-substituent. Compounds
      7a and 14d interact with the P-loop whereas 14a and 14b engage with Thr217 in the
      post-hinge region. These crystallographic insights provide options for the design
      of compounds interacting with the DFG motif or with Thr217. 

PMID- 26296480
TI  - Letter From the Guest Editor: Magnetic Resonance Imaging in Obstetrics and
      Gynecology.

PMID- 26296481
TI  - Current Role of Fetal Magnetic Resonance Imaging in Neurologic Anomalies.
AB  - Magnetic resonance imaging (MRI) is used increasingly to image the fetus when
      important questions remain unanswered after ultrasonography, which might occur
      particularly with abnormal amniotic fluid volumes, difficult fetal lie or
      position, and maternal obesity. Ultrasonography also has limitations due to sound
      attenuation by bone, such as within the cranium and spine, and therefore MRI has
      a real advantage in delineating potentially complex neuroanatomical
      relationships. This article outlines current MRI protocols for evaluation of the
      fetal neural axis, describes indications for the use of MRI in the fetal brain
      and spine, and provides examples to illustrate the uses of available fetal
      sequences. 

PMID- 26296479
TI  - Quality indicators for the management of Barrett's esophagus, dysplasia, and
      esophageal adenocarcinoma: international consensus recommendations from the
      American Gastroenterological Association Symposium.
AB  - The development of and adherence to quality indicators in gastroenterology, as in
      all of medicine, is increasing in importance to ensure that patients receive
      consistent high-quality care. In addition, government-based and private insurers
      will be expecting documentation of the parameters by which we measure quality,
      which will likely affect reimbursements. Barrett's esophagus remains a
      particularly important disease entity for which we should maintain up-to-date
      guidelines, given its commonality, potentially lethal outcomes, and controversies
      regarding screening and surveillance. To achieve this goal, a relatively large
      group of international experts was assembled and, using the modified Delphi
      method, evaluated the validity of multiple candidate quality indicators for the
      diagnosis and management of Barrett's esophagus. Several candidate quality
      indicators achieved >80% agreement. These statements are intended to serve as a
      consensus on candidate quality indicators for those who treat patients with
      Barrett's esophagus. 

PMID- 26296482
TI  - Current Role of Fetal Magnetic Resonance Imaging in Body Anomalies.
AB  - Fetal MR body applications have become more common in recent years as both in
      utero therapies, including fetoscopic surgery, and improvements in perinatal care
      have increased the demand for precise antenatal anatomic detail. This article
      discusses the variety of fast imaging sequences available to the fetal imager and
      describes their applications to both common and unusual congenital pathologies,
      including of the neck, chest, abdomen/pelvis and musculoskeletal systems. 

PMID- 26296483
TI  - Morbidly Adherent Placenta: Ultrasound Assessment and Supplemental Role of
      Magnetic Resonance Imaging.
AB  - Morbidly adherent placenta or placenta accreta is being increasingly encountered
      in obstetrical practice mainly owing to the increasing rates of cesarean
      delivery. This condition is associated with increased maternal morbidity and
      mortality resulting from postpartum hemorrhage. When unsuspected, outcomes can be
      catastrophic to the pregnant woman. Timely diagnosis during the antenatal period,
      on the contrary, allows for optimal planning of a multidisciplinary management
      approach and delivery at a tertiary care institution. A higher index of suspicion
      in those at greatest risk such as in women with placenta previa and with history
      of some prior cesarean deliveries should lead to diligent antenatal evaluation
      for possible placenta accreta. Management of invasive placenta implantation often
      involves cesarean delivery hysterectomies; uterus-sparing alternatives to manage
      this condition can be an option in selected cases. Ultrasound imaging remains the
      modality of choice for the diagnosis. This review article discusses the
      ultrasound image findings in placenta accreta, its limitations and pitfalls, and
      the supplemental role of magnetic resonance imaging in the imaging evaluation of
      placenta accreta. 

PMID- 26296484
TI  - Magnetic Resonance Imaging of Developmental Anomalies of the Uterus and the
      Vagina in Pediatric Patients.
AB  - Developmental anomalies of the uterus and the vagina are associated with
      infertility and miscarriage and are most commonly detected in the postpubertal
      age-group. These conditions may also present in younger patients as a mass or
      pain owing to obstruction of the uterus or the vagina. Associated urinary tract
      anomalies are common, as well. Accurate diagnosis and thorough description of
      these anomalies is essential for appropriate management; however, evaluation may
      be difficult in an immature reproductive tract. Magnetic resonance imaging
      technique pertinent to imaging of the pediatric female reproductive tract is
      presented and illustrated along with the findings associated with various
      anomalies. 

PMID- 26296485
TI  - Magnetic Resonance Imaging of Benign and Malignant Uterine Neoplasms.
AB  - Benign and malignant uterine masses can be seen in the women. Some of these are
      asymptomatic and incidentally discovered, whereas others can be symptomatic. With
      the soft tissue contrast resolution magnetic resonance imaging can render a
      definitive diagnosis, which can further help streamline patient management. In
      this article we show magnetic resonance imaging examples of benign and malignant
      masses of the uterus and their treatment strategies. 

PMID- 26296486
TI  - Magnetic Resonance Imaging in the Diagnosis, Staging, and Surveillance of
      Cervical Carcinoma.
AB  - Cervical carcinoma remains a common gynecologic malignancy. Magnetic resonance
      imaging is a useful and accurate tool in the diagnosis, staging, and follow-up of
      cervical carcinoma. This article describes the optimal techniques for magnetic
      resonance evaluation of the cervix, illustrates the role of magnetic resonance
      imaging in patients with known or indicated cervical carcinoma, and describes key
      aspects of staging and management of cervical carcinoma. 

PMID- 26296487
TI  - Adnexal Masses: Role of Supplemental Imaging With Magnetic Resonance Imaging.
AB  - Sonography is the primary and often the only imaging modality used for evaluation
      of an adnexal mass. Grayscale sonography with color and spectral Doppler imaging
      is able to accurately characterize most of the adnexal masses. Supplemental
      imaging with computed tomography and magnetic resonance imaging (MRI) is useful
      in selected cases. Computed tomography is preferred for evaluation of bowel
      related pathology masquerading as an adnexal mass and for staging of gynecologic
      cancers. Owing to its superior contrast resolution and multiplanar imaging
      capability, MRI is helpful in characterizing an indeterminate adnexal mass, as
      well as determining the organ of origin of an adnexal mass. MRI thereby allows
      planning of appropriate surgical or nonsurgical management of neoplastic and
      nonneoplastic conditions affecting the adnexa. Imaging evaluation of adnexal
      masses and the supplemental role of MRI in the management of adnexal masses are
      discussed. 

PMID- 26296488
TI  - Pelvic Endometriosis: Spectrum of Magnetic Resonance Imaging Findings.
AB  - Endometriosis is defined as the presence of endometrial tissue outside the
      uterus. It is a common cause of pelvic pain and infertility among reproductive
      age women. Although laparoscopy remains the reference standard for diagnosis,
      this invasive procedure provides little information on subperitoneal extent of
      disease or areas hidden by adhesions. In contrast, magnetic resonance imaging
      (MRI) provides a comprehensive, noninvasive survey of the pelvis with
      simultaneous tissue characterization. In this article, we review the spectrum of
      MRI findings in pelvic endometriosis and discuss common complications associated
      with the disease. Radiologists should be familiar with the spectrum of MRI
      findings of pelvic endometriosis so that they can provide meaningful information
      that will guide treatment and future laparoscopic examinations. 

PMID- 26296489
TI  - mTORC1 and mTORC2 have largely distinct functions in Purkinje cells.
AB  - The mammalian target of rapamycin (mTOR) is a key regulator of cellular growth
      which associates with other proteins to form two multi-protein complexes called
      mTORC1 and mTORC2. Dysregulation of mTORC1 signalling in brain is implicated in
      neuropathological conditions such as autism spectrum or neurodegenerative
      disorders. Accordingly, allosteric mTOR inhibitors are currently in clinical
      trials for the treatment of such disorders. Here, we ablated either mTORC1 or
      mTORC2 conditionally in Purkinje cells of the mouse cerebellum to dissect their
      role in the development, function and survival of these neurons. We find that the
      two mouse models largely differ from each other by phenotype and cellular
      responses. Inactivation of mTORC2, but not of mTORC1, led to motor coordination
      deficits at an early age. This phenotype correlated with developmental deficits
      in climbing fibre elimination and impaired dendritic self-avoidance in mTORC2
      deficient Purkinje cells. In contrast, inactivation of mTORC1, but not of mTORC2,
      affected social interest of the mice and caused a progressive loss of Purkinje
      cells due to apoptosis. This cell loss was paralleled by age-dependent motor
      deficits. Comparison of mTORC1-deficient Purkinje cells with those deficient for
      the mTORC1 inhibitor TSC1 revealed a striking overlap in Purkinje cell
      degeneration and death, which included neurofilamentopathy and reactive gliosis.
      Altogether, our study reveals distinct roles of mTORC1 and mTORC2 in Purkinje
      cells for mouse behaviour and the survival of neurons. Our study also highlights
      a convergence between the phenotypes of Purkinje cells lacking mTORC1 activity
      and those expressing constitutively active mTORC1 due to TSC1 deficiency. 

PMID- 26296490
TI  - Nemaline body myopathy caused by a novel mutation in troponin T1 (TNNT1).
AB  - INTRODUCTION: Nemaline myopathy is a rare disorder characterized by skeletal
      muscle weakness of varying severity and onset, with the presence of nemaline rods
      on muscle biopsy. Congenital nemaline body myopathy due to mutations in TNNT1 has
      hitherto only been described as a result of a single founder mutation in patients
      of Amish origin and in 2 other individuals with different recessive mutations.
      METHODS: Autozygosity mapping and whole exome sequencing were applied after we
      identified 9 Palestinian patients from 7 unrelated families who have nemaline
      myopathy. RESULTS: All patients were homozygous for a novel complex rearrangement
      of the TNNT1 gene (c.574_577delinsTAGTGCTGT | NM_003283) leading to C-terminal
      truncation of the protein (p.L203* | NP_003274.3). Their clinical course was
      remarkable for early respiratory failure and striking stiffness of the cervical
      spine. CONCLUSIONS: This report exemplifies the utility of combining autozygosity
      mapping and whole exome sequencing and expands the phenotype associated with
      TNNT1 mutations.

PMID- 26296491
TI  - Hexon-modified recombinant E1-deleted adenoviral vectors as bivalent vaccine
      carriers for Coxsackievirus A16 and Enterovirus 71.
AB  - Hand, foot and mouth disease (HFMD) is a major public health concern in Asia;
      more efficient vaccines against HFMD are urgently required. Adenoviral (Ad)
      capsids have been used widely for the presentation of foreign antigens to induce
      specific immune responses in the host. Here, we describe a novel bivalent vaccine
      for HFMD based on the hexon-modified, E1-deleted chimpanzee adenovirus serotype
      68 (AdC68). The novel vaccine candidate was generated by incorporating the
      neutralising epitope of Coxsackievirus A16 (CA16), PEP71, into hypervariable
      region 1 (HVR1), and a shortened neutralising epitope of Enterovirus 71 (EV71),
      sSP70, into HVR2 of the AdC68 hexon. In order to enhance the immunogenicity of
      EV71, VP1 of EV71 was cloned into the E1-region of the AdC68 vectors. The results
      demonstrated that these two epitopes were well presented on the virion surface
      and had high affinity towards specific antibodies, and VP1 of EV71 was also
      significantly expressed. In pre-clinical mouse models, the hexon-modified AdC68
      elicited neutralising antibodies against both CA16 and EV71, which conferred
      protection to suckling mice against a lethal challenge of CA16 and EV71. In
      summary, this study demonstrates that the hexon-modified AdC68 may represent a
      promising bivalent vaccine carrier against EV71 and CA16 and an epitope-display
      platform for other pathogens.

PMID- 26296492
TI  - Influenza vaccine acceptance among pregnant women in urban slum areas, Karachi,
      Pakistan.
AB  - BACKGROUND: Facilitators and barriers to influenza vaccination among pregnant
      women in the developing world are poorly understood, particularly in South Asia.
      We assessed intention to accept influenza vaccine among ethnically diverse low
      income pregnant women in Pakistan. METHODS: From May to August 2013, we conducted
      a cross-sectional survey of pregnant women who visited health centers in urban
      slums in Karachi city. We assessed intention to accept influenza vaccine against
      socio-demographic factors, vaccination history, vaccine recommendation sources,
      and other factors. RESULTS: In an unvaccinated study population of 283
      respondents, 87% were willing to accept the vaccine, if offered. All except two
      participants were aware of symptoms typically associated with influenza.
      Perceived vaccine safety, efficacy, and disease susceptibility were significantly
      associated with intention to accept influenza vaccine (p<0.05). Regardless of
      intention to accept influenza vaccine, 96% rated healthcare providers as highly
      reliable source of vaccine information. While a recommendation from a physician
      was critical for influenza vaccine acceptance, parents-in-law and husbands were
      often considered the primary decision-makers for pregnant women seeking
      healthcare including vaccination. CONCLUSIONS: Maternal influenza vaccination
      initiatives in South Asia should strongly consider counseling of key familial
      decision-makers and inclusion of healthcare providers to help implement new
      vaccination programs.

PMID- 26296493
TI  - Evaluation of pentavalent rotavirus vaccination in neonatal intensive care units.
AB  - BACKGROUND & OBJECTIVES: Preterm infants are at highest risk for severe rotavirus
      gastroenteritis. While rotavirus vaccination is recommended for age-eligible,
      clinically stable preterm infants, controversy exists regarding vaccination of
      these infants during hospitalization. The objectives of this study were to
      examine tolerance of pentavalent rotavirus vaccination (RV5) among hospitalized
      infants and nosocomial rotavirus transmission in the neonatal intensive care
      units (NICU) at two urban hospitals. METHODS: A retrospective, medical chart
      review of patients receiving RV5 vaccine was conducted to examine clinical
      histories of vaccine recipients. Average risk differences of gastrointestinal
      complications were estimated between the three days prior and up to four weeks
      following RV5 vaccination. A generalized linear regression model was used to
      examine the association between days since RV5 administration and daily feeding
      totals, using fixed effects to account for individual-level clustering. Rates of
      nosocomial rotavirus from active surveillance were compared between pre- and post
      NICU-based vaccination periods. RESULTS: From July 1, 2011 to March 30, 2013, RV5
      vaccination was initiated for 102 NICU patients. No changes in the average risk
      of gastrointestinal complications or daily feeding among participants overall
      were detected following RV5 administration. Rates of nosocomial rotavirus were
      similar during the periods before and after NICU-based vaccination. CONCLUSIONS:
      On average, RV5 appeared to be well tolerated among vaccine recipients, with no
      increase in nosocomial rotavirus transmission observed following NICU-based
      rotavirus vaccination. While the benefits of a RV5 NICU-based vaccination program
      for otherwise eligible preterm infants seem to outweigh the possible risk of
      vaccine virus transmission, further studies are needed.

PMID- 26296494
TI  - Usage of quadrivalent influenza vaccine among children in the United States, 2013
      14.
AB  - Annual influenza vaccination is recommended for everyone >= 6 months in the U.S.
      During the 2013-14 influenza season, in addition to trivalent influenza vaccines,
      quadrivalent vaccines were available, protecting against two influenza A and two
      influenza B viruses. We analyzed 1,976,443 immunization records from six sentinel
      sites to compare influenza vaccine usage among children age 6 months-18 years. A
      total of 983,401 (49.8%) influenza vaccine doses administered were trivalent and
      920,333 (46.6%) were quadrivalent (unknown type: 72,709). Quadrivalent vaccine
      administration varied by age and was least frequent among those <2 years of age.

PMID- 26296495
TI  - Enhanced therapeutic effect of APAVAC immunotherapy in combination with dose
      intense chemotherapy in dogs with advanced indolent B-cell lymphoma.
AB  - The aim of this non-randomized controlled trial was to compare time to
      progression (TTP), lymphoma-specific survival (LSS), and safety of an autologous
      vaccine (consisting of hydroxyapatite ceramic powder and Heat Shock Proteins
      purified from the dogs' tumors, HSPPCs-HA) plus chemotherapy versus chemotherapy
      alone in dogs with newly diagnosed, clinically advanced, histologically
      confirmed, multicentric indolent B-cell lymphoma. The vaccine was prepared from
      dogs' resected lymph nodes and administered as an intradermal injection. Forty
      five client-owned dogs were enrolled: 20 dogs were treated with dose-intense
      chemotherapy, and 25 received concurrent immunotherapy. Both treatment arms were
      well tolerated, with no exacerbated toxicity in dogs also receiving the vaccine.
      TTP was significantly longer for dogs treated with chemo-immunotherapy versus
      those receiving chemotherapy only (median, 209 versus 85 days, respectively,
      P=0.015). LSS was not significantly different between groups: dogs treated with
      chemo-immunotherapy had a median survival of 349 days, and those treated with
      chemotherapy only had a median survival of 200 days (P=0.173). Among vaccinated
      dogs, those mounting an immune response had a significantly longer TTP and LSS
      than those with no detectable response (P=0.012 and P=0.003, respectively).
      Collectively these results demonstrate that vaccination with HSPPCs-HA may
      produce clinical benefits with no increased toxicity, thereby providing a
      strategy for enhancing chemotherapy in dogs with advanced indolent lymphoma.

PMID- 26296496
TI  - Influenza vaccination and risk of stroke: Self-controlled case-series study.
AB  - BACKGROUND: Stroke may be triggered by respiratory infections, including
      influenza. Influenza vaccination could therefore reduce risk of stroke. Previous
      studies of this association have shown conflicting results. We aimed to
      investigate whether influenza vaccination was associated with reduced risk of
      stroke. METHODS: We used a self-controlled case series design. The General
      Practice Research Database (GPRD) was used to extract records of patients aged 18
      years or over recorded with stroke (fatal or non-fatal) from September 2001 to
      May 2009. Statistical modelling with conditional Poisson regression was employed
      to compute incidence rate ratios (IRR). The incidence rate of stroke in fixed
      time periods after influenza vaccination was compared with the incidence rate
      during a baseline period. RESULTS: There were 17,853 eligible individuals who
      received one or more influenza vaccinations and experienced a stroke during the
      observation period. The incidence of stroke was significantly reduced in the
      first 59 days following influenza vaccination compared with the baseline period.
      We found reductions of 55% (IRR 0.45; 95% CI 0.36-0.57) in the first 1-3 days
      after vaccination, 36% (0.64; 0.53-0.76) at 4-7 days, 30% (0.70; 0.61-0.79) at 8
      14 days, 24% (0.76; 0.70-0.84) at 15-28 days and 17% (0.83; 0.77-0.89) at 29-59
      days after vaccination. Early vaccination between 1 September and 15 November
      showed a greater reduction in IRR compared to later vaccination given after mid
      November. CONCLUSIONS: Influenza vaccination is associated with a reduction in
      incidence of stroke. This study supports previous studies which have shown a
      beneficial association of influenza vaccination for stroke prevention.

PMID- 26296498
TI  - Effective cutaneous vaccination using an inactivated chikungunya virus vaccine
      delivered by Foroderm.
AB  - Foroderm is a new cutaneous delivery technology that uses high-aspect ratio,
      cylindrical silica microparticles, that are massaged into the skin using a 3D
      printed microtextured applicator, in order to deliver payloads across the
      epidermis. Herein we show that this technology is effective for delivery of a non
      adjuvanted, inactivated, whole-virus chikungunya virus vaccine in mice, with
      minimal post-vaccination skin reactions. A single topical Foroderm-based
      vaccination induced T cell, Th1 cytokine and antibody responses, which provided
      complete protection against viraemia and disease after challenge with chikungunya
      virus. Foroderm vaccination was shown to deliver fluorescent, virus-sized beads
      across the epidermis, with beads subsequently detected in draining lymph nodes.
      Foroderm vaccination also stimulated the egress of MHC II(+) antigen presenting
      cells from the skin. Foroderm thus has potential as a simple, cheap, effective,
      generic, needle-free technology for topical delivery of vaccines.

PMID- 26296497
TI  - Clinical testing of pre-pandemic live attenuated A/H5N2 influenza candidate
      vaccine in adult volunteers: results from a placebo-controlled, randomized double
      blind phase I study.
AB  - BACKGROUND: This study describes a double-blinded randomized placebo-controlled
      phase I clinical trial of A/H5N2 live attenuated influenza vaccine in healthy
      volunteers. METHODS: Two doses of vaccine or placebo were administered
      intranasally to 30 and 10 subjects, respectively. Nasal swabs were examined for
      vaccine shedding and local antibody responses; serum samples were tested for
      binding, hemagglutinating and neutralizing antibodies and peripheral blood
      mononuclear cells were tested for cell-mediated immune responses. RESULTS: The
      vaccine was well tolerated and not associated with increased rates of adverse
      events or the occurrence of serious adverse events. Influenza virus was detected
      in nasal swabs on the first day in the majority of volunteers (93%), while 17% of
      volunteers tested positive on the second, none on the third day or later
      following the first vaccination; lower frequency of shedding was observed after
      the second vaccination. The vaccine was immunogenic as assessed four weeks after
      the second dose, with 37.9% and 48.3% of subjects seroconverting by
      hemagglutination inhibition and neutralization assays, respectively. An immune
      response was observed in 96.6% subjects that received A/H5N2 LAIV in at least one
      of the assays conducted. None of the placebo recipients exhibited a response in
      any of the assays. CONCLUSION: The A/H5N2 vaccine was safe, well tolerated, and
      immunogenic in healthy adults. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT01719783.

PMID- 26296499
TI  - Rift Valley fever virus: A review of diagnosis and vaccination, and implications
      for emergence in Europe.
AB  - Rift Valley fever virus (RVFV) is a mosquito-borne virus, and is the causative
      agent of Rift Valley fever (RVF), a zoonotic disease characterised by an
      increased incidence of abortion or foetal malformation in ruminants. Infection in
      humans can also lead to clinical manifestations that in severe cases cause
      encephalitis or haemorrhagic fever. The virus is endemic throughout much of the
      African continent. However, the emergence of RVFV in the Middle East, northern
      Egypt and the Comoros Archipelago has highlighted that the geographical range of
      RVFV may be increasing, and has led to the concern that an incursion into Europe
      may occur. At present, there is a limited range of veterinary vaccines available
      for use in endemic areas, and there is no licensed human vaccine. In this review,
      the methods available for diagnosis of RVFV infection, the current status of
      vaccine development and possible implications for RVFV emergence in Europe, are
      discussed. 

PMID- 26296500
TI  - Identifying functional subdivisions in the human brain using meta-analytic
      activation modeling-based parcellation.
AB  - Parcellation of the human brain into fine-grained units by grouping voxels into
      distinct clusters has been an effective approach for delineating specific brain
      regions and their subregions. Published neuroimaging studies employing coordinate
      based meta-analyses have shown that the activation foci and their corresponding
      behavioral categories may contain useful information about the anatomical
      functional organization of brain regions. Inspired by these developments, we
      proposed a new parcellation scheme called meta-analytic activation modeling-based
      parcellation (MAMP) that uses meta-analytically obtained information. The raw
      meta data, including the experiments and the reported activation coordinates
      related to a brain region of interest, were acquired from the Brainmap database.
      Using this data, we first obtained the "modeled activation" pattern by modeling
      the voxel-wise activation probability given spatial uncertainty for each
      experiment that featured at least one focus within the region of interest. Then,
      we processed these "modeled activation" patterns across the experiments with a K
      means clustering algorithm to group the voxels into different subregions. In
      order to verify the reliability of the method, we employed our method to
      parcellate the amygdala and the left Brodmann area 44 (BA44). The parcellation
      results were quite consistent with previous cytoarchitectonic and in vivo
      neuroimaging findings. Therefore, the MAMP proposed in the current study could be
      a useful complement to other methods for uncovering the functional organization
      of the human brain.

PMID- 26296502
TI  - Reliable survival analysis based on the Dirichlet process.
AB  - We present a robust Dirichlet process for estimating survival functions from
      samples with right-censored data. It adopts a prior near-ignorance approach to
      avoid almost any assumption about the distribution of the population lifetimes,
      as well as the need of eliciting an infinite dimensional parameter (in case of
      lack of prior information), as it happens with the usual Dirichlet process prior.
      We show how such model can be used to derive robust inferences from right
      censored lifetime data. Robustness is due to the identification of the decisions
      that are prior-dependent, and can be interpreted as an analysis of sensitivity
      with respect to the hypothetical inclusion of fictitious new samples in the data.
      In particular, we derive a nonparametric estimator of the survival probability
      and a hypothesis test about the probability that the lifetime of an individual
      from one population is shorter than the lifetime of an individual from another.
      We evaluate these ideas on simulated data and on the Australian AIDS survival
      dataset. The methods are publicly available through an easy-to-use R package. 

PMID- 26296501
TI  - Mapping the mouse brain with rs-fMRI: An optimized pipeline for functional
      network identification.
AB  - The use of resting state fMRI (rs-fMRI) in translational research is a powerful
      tool to assess brain connectivity and investigate neuropathology in mouse models.
      However, despite encouraging initial results, the characterization of consistent
      and robust resting state networks in mice remains a methodological challenge. One
      key reason is that the quality of the measured MR signal is degraded by the
      presence of structural noise from non-neural sources. Notably, in the current
      pipeline of the Human Connectome Project, a novel approach has been introduced to
      clean rs-fMRI data, which involves automatic artifact component classification
      and data cleaning (FIX). FIX does not require any external recordings of
      physiology or the segmentation of CSF and white matter. In this study, we
      evaluated the performance of FIX for analyzing mouse rs-fMRI data. Our results
      showed that FIX can be easily applied to mouse datasets and detects true signals
      with 100% accuracy and true noise components with very high accuracy (>98%), thus
      reducing both within- and between-subject variability of rs-fMRI connectivity
      measurements. Using this improved pre-processing pipeline, maps of 23 resting
      state circuits in mice were identified including two networks that displayed
      default mode network-like topography. Hierarchical clustering grouped these
      neural networks into meaningful larger functional circuits. These mouse resting
      state networks, which are publicly available, might serve as a reference for
      future work using mouse models of neurological disorders. 

PMID- 26296503
TI  - Morphine preconditioning confers cardioprotection in doxorubicin-induced failing
      rat hearts via ERK/GSK-3beta pathway independent of PI3K/Akt.
AB  - Preconditioning against myocardial ischemia-reperfusion (I/R) injury can be
      suppressed in some pathological conditions. This study was designed to
      investigate whether morphine preconditioning (MPC) exerts cardioprotection in
      doxorubicin (DOX)-induced heart failure in rats and the mechanisms involved.
      Phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt), extracellular signal
      regulated kinase (ERK) and glycogen synthase kinase (GSK)-3beta pathways were
      examined. Normal and DOX-induced failing rat hearts were subjected to I/R injury
      using a Langendorff perfusion system with or without MPC or ischemic
      preconditioning (IPC). The PI3K inhibitor (wortmannin) or ERK inhibitor (PD98059)
      was infused before MPC. In normal hearts, both MPC and IPC significantly reduced
      infarct size and the rise in lactate dehydrogenase (LDH) level caused by I/R
      injury. Pretreatment with wortmannin or PD98059 abrogated the protective effects
      of MPC and suppressed the phosphorylation of Akt, ERK and GSK-3beta. In failing
      rat hearts, however, MPC retained its cardioprotection while IPC did not. This
      protective effect was abolished by PD98059 but not wortmannin. MPC increased the
      level of p-ERK rather than p-Akt. The phosphorylation of GSK-3beta induced by MPC
      was reversed by PD98059 only. IPC did not elevate the expression of p-ERK, p-Akt
      and p-GSK-3beta in failing rat hearts. We conclude that MPC is cardioprotective
      in rats with DOX-induced heart failure while IPC is not. The effect of MPC
      appears to be mediated via the ERK/GSK-3beta pathway independent of PI3K/Akt. 

PMID- 26296504
TI  - Response of biochemical biomarkers in the aquatic crustacean Daphnia magna
      exposed to silver nanoparticles.
AB  - The proliferation of silver nanoparticle (AgNP) production and use owing to their
      antimicrobial properties justifies the need to examine the resulting
      environmental impacts. The discharge of biocidal nanoparticles to water bodies
      may pose a threat to aquatic species. This study evaluated the effects of citrate
      coated AgNPs on the standardized test organism Daphnia magna Straus clone MBP996
      by means of biochemical biomarker response. AgNP toxicity was compared against
      the toxic effect of Ag(+). The toxicity endpoints were calculated based upon
      measured Ag concentrations in exposure media. For AgNPs, the NOAEC and LOAEC
      values at 48 h were 5 and 7 MUg Ag/L, respectively, while these values were 0.5
      and 1 MUg Ag/L, respectively, for Ag(+). The EC50 at 48 h was computed to be 12.4
      +/- 0.6 and 2.6 +/- 0.1 MUg Ag/L for AgNPs and Ag(+), respectively, with 95 %
      confidence intervals of 12.1-12.8 and 2.3-2.8 MUg Ag/L, respectively. These
      results indicate significant less toxicity of AgNP compared to free Ag(+) ions.
      Five biomarkers were evaluated in Daphnia magna neonates after acute exposure to
      Ag(+) or AgNPs, including glutathione (GSH) level, reactive oxygen species (ROS)
      content, and catalase (CAT), acetylcholinesterase (AChE), and superoxide
      dismutase (SOD) activity. AgNPs induced toxicity and oxidative stress responses
      in D. magna neonates at tenfold higher concentrations than Ag. Biochemical
      methods revealed a clear increase in AChE activity, decreased ROS level,
      increased GSH level and CAT activity, but no significant changes in SOD activity.
      As Ag(+) may dissolve from AgNPs, these two types of Ag could act synergistically
      and produce a greater toxic response. The observed remarkably high toxicity of
      AgNPs (in the parts-per-billion range) to crustaceans indicates that these
      organisms are a vulnerable link in the aquatic food chain with regard to
      contamination by nanosilver. Graphical Abstract ?.

PMID- 26296505
TI  - Impact of tributyltin on antioxidant and DNA damage response in spermatozoa of
      freshwater prawn Macrobrachium rosenbergii.
AB  - Effects of tributyltin (TBT) on antioxidant [total superoxide dismutase (SOD),
      glutathione peroxidase (GPx), and glutathione reductase (GR)] and DNA damage
      levels in the spermatozoa were studied and reported here for the first time in
      the freshwater prawn Macrobrachium rosenbergii. Three groups of (n = 10 in each
      group) fishes were exposed to three different nominal concentrations of TBT viz.,
      1, 2, and 4 mg L(-1) along with control group for 90 days. Significant decrease
      of antioxidant and increased DNA damage levels were seen at higher doses of 2 and
      4 mg L(-1). In prawn, the antioxidant level plays a vital role in sperm
      protection, activation, differential functions related to the physiology, and
      reproductive behavior. This study serves as a biomonitoring tool to assess the
      TBT effects on reproductive behavior of aquatic biota.

PMID- 26296506
TI  - Application of a Sediment Quality Index for the assessment and monitoring of
      metals and organochlorines in a premier conservation area.
AB  - The physical and chemical characteristics of surface sediments from a leading
      conservation area, namely the Kruger National Park, were determined in order to
      identify potential stressors in the systems that may contribute to overall
      deterioration in sediment quality within the reserve, leading to potential
      threats to the aquatic biota conserved within these stretches of river. Sediment
      samples were collected during four surveys (two low flow and two high flow) from
      2009 to 2011. Samples were analysed for organic content, grain size
      determination, metals and various organochlorine pesticides. Results indicated
      that the Olifants River sediments did not show any great improvement over the
      years and point towards the continued input of pollutants into this system.
      Sediment quality in the Luvuvhu and Letaba Rivers is better than that of
      sediments from the Olifants River in terms of metals, but metal concentrations
      are still comparable and point towards anthropogenic inputs of metals into these
      rivers. Even though the data indicate that these systems are being contaminated
      with both metals and organochlorine pesticides (OCPs), levels were still below
      contaminated sediments from around the globe. Sediment Quality Index scores
      showed that the sediment quality of these rivers is in a relatively good state.
      High metal concentrations were the drivers behind lowered sediment quality, and
      in some cases certain OCPs played a role. Both metals and OCP concentrations were
      highly correlated with finer grain sizes. Sediment assessments are not routinely
      applied in South Africa resulting in very little reference or background data
      available for the area. The metal concentrations for the study area were
      generally lower than those for other studies in more polluted regions. The study
      also contributes to the available knowledge on surrounding metal pollution in
      riverine sediments in South Africa.

PMID- 26296507
TI  - Synthesis and characterization of gamma-ferric oxide nanoparticles and their
      effect on Solanum lycopersicum.
AB  - gamma-Ferric oxide nanoparticles are synthesized through modern and facile
      ayurvedic route followed by normal and special purification steps, which are both
      cost-effective and eco-friendly. These synthesized gamma-ferric oxide
      nanoparticles were applied on Solanum lycopersicum to search the effect on
      chlorophyll content. This process involves multiple filtration and calcination
      steps. The synthesized samples were analyzed by X-ray diffraction (XRD), UV
      visible (UV-vis) spectroscopy, transmission electron microscopy (TEM), vibrating
      sample magnetometry (VSM), and particle size analysis (PSA) to identify the
      purification step's influence on the structural, optical, morphological,
      magnetic, and particle size properties of ferric oxide nanoparticles (gamma
      phase). X-ray diffraction has revealed that ferric oxide nanoparticles have
      rhombohedral structure of alpha-phase (hematite) in initial purification process
      later transformed into cubic structure gamma-phase (maghemite). UV-vis
      spectroscopy analysis has clearly shown that by repetitive purification steps,
      lambdamax has increased from 230 to 340 nm. TEM result has an intercorrelation
      with XRD results. gamma-Ferric oxide nanoparticles were tested on Solanum
      lycopersicum (tomato seeds). The changes in the contents of chlorophyll a,
      chlorophyll b, and total carotene were studied using spectral measurements at two
      different dosages-0.5 and 2 M. As a result, at 0.5-M concentration, magnetic
      nanoparticles exhibit fruitful results by increasing the crop yield and being
      more resistant to chlorosis. 

PMID- 26296508
TI  - Current clinical features in diagnosis and treatment for immaturity of ganglia in
      Japan: analysis from 10-year nationwide survey.
AB  - BACKGROUND: To identify the current clinical features in diagnosis and treatment
      for immaturity of ganglia (IG) in Japan, we retrospectively analyzed data for
      patients with IG from the nationwide surveys in Japan. This survey was performed
      by Japanese Study Group of allied disorders of Hirschsprung's disease (ADHD).
      METHODS: In primary research, data on totally 355 cases of ADHD were collected
      for 10 years (2001-2010). Fifteen patients were IG. All IG patients were
      confirmed by pathological examination. In secondary research, detail
      questionnaires were sent and collected. RESULTS: Male/female ratio was 9/6 and
      mean birth weight was 2474 g. All cases (100 %) were onset in neonatal period.
      Primary symptoms were abdominal distention (86.7 %), vomiting (53.3 %), and late
      egestion of meconium (26.7 %). An abnormal distention of intestine was recognized
      in 86.7 % on X-ray, and microcolon was recognized in 58.3 % on contrast enema.
      Caliber change was recognized in 58.3 % on laparotomy. An enterostomy was made in
      13 patients (86.7 %), and an ileostomy was made in 69.2 %. Pathological diagnosis
      was performed in 100 %. Enterostomy was closed in 100 %. CONCLUSIONS: Totally, 15
      definitive cases of IG in 10 years were collected and analyzed. All cases were
      onset in the neonatal period and almost all underwent enterostomy, but no
      mortalities occurred.

PMID- 26296509
TI  - [Anastomosis and suture insufficiency after interventions for bariatric and
      metabolic surgery].
AB  - BACKROUND: Metabolic surgery is internationally well-established for the
      treatment of obesity and its comorbidities. The numbers of procedures performed
      is steadily increasing. The results of surgery are superior in comparison to
      conservative treatment options regarding weight loss and resolution of
      comorbidities. The insufficiency of suture lines is a well-known and feared
      complication in the stapling procedures and is associated with an increased
      morbidity as well as mortality, especially in super obese patients. MATERIAL AND
      METHODS: The current literature was reviewed and the results are reported within
      the context of own experience. RESULTS: The most severe complications are staple
      line leakage after sleeve gastrectomy, leakage of anastomoses after bypass
      procedures and duodenal stump insufficiency. For the treatment of sleeve leakage
      various endoscopic procedures, such as over the scope (OTS) clips, stents and
      endoluminal vacuum therapy are available. Surgical revision, such as
      oversuturing, drainage and redo surgery are well-established. The management of
      all other complications is mainly by surgical intervention. Intraoperative
      standardization of procedures and knowledge of the physical foundations are
      essential for the prevention of leakage. Several preventive methods are available
      but randomized controlled trials are missing. CONCLUSION: The therapy of leakages
      in the field of bariatric surgery is an interdisciplinary approach and dependent
      on the available resources in the treating hospital. The data reported show good
      results but the different reports published are inconsistent. Leakages often do
      not occur in the immediate postoperative period but in the sense of a long-term
      complication; therefore standardization of procedures and follow-up as well as
      complication management is mandatory. Randomized controlled studies must be
      promoted.

PMID- 26296510
TI  - [Complication management of infected osteosynthesis: Therapy algorithm for peri
      implant infections].
AB  - BACKGROUND: Peri-implant infections (PII) are one of the most frequent
      postoperative complications and require an individualized combined surgical and
      antibiotic management. In this review article we provide up to date scientific
      knowledge regarding the pathogenesis, classification, diagnosis and therapy of
      PII. The aim of this article is to explain the rational background and evidence
      of individual treatment options in order to elaborate concrete management
      recommendations. MATERIAL AND METHODS: The relevant scientific publications were
      critically reviewed for diagnostics, therapy and prevention of PII. Based on
      these data we present a combined surgical and antibiotic treatment algorithm for
      PII. RESULTS: With a consistent interdisciplinary action high healing rates with
      eradication of PII can be achieved. In acute PII (< 6 weeks) the implant can
      normally be retained but this is dependent on the soft tissue conditions, while
      in chronic PII (> 6 weeks) the implant generally has to be removed in a one or
      two step exchange, depending on the soft tissue, bone defects and pathogen.
      CONCLUSION: Scientific knowledge and clinical data have led to new treatment
      algorithms for PII with improved outcome, decreased morbidity and shortened
      hospitalization. Systemic individualized antimicrobial therapy, radical septic
      and plastic surgery are the cornerstones for successful treatment of acute and
      chronic PII. The local use of antibiotics and application of bone substitute
      materials are other techniques for treatment but the exact importance must still
      be determined.

PMID- 26296512
TI  - Suicide risk is elevated in migraineurs who  have comorbid fibromyalgia.

PMID- 26296511
TI  - Perampanel for tonic-clonic seizures in  idiopathic generalized epilepsy  A
      randomized trial.
AB  - OBJECTIVE: To assess efficacy and safety of adjunctive perampanel in patients
      with drug-resistant, primary generalized tonic-clonic (PGTC) seizures in
      idiopathic generalized epilepsy (IGE). METHODS: In this multicenter, double-blind
      study (ClinicalTrials.gov identifier: NCT01393743; funded by Eisai Inc.),
      patients 12 years or older with PGTC seizures and IGE were randomized to placebo
      or perampanel during a 4-week titration period (perampanel up titrated from 2 to
      8 mg/d, or highest tolerated dose) and 13-week maintenance period. The primary
      endpoint was percent change in PGTC seizure frequency per 28 days (titration plus
      maintenance vs baseline). The key secondary endpoint (primary endpoint for
      European Union registration) was 50% PGTC seizure responder rate (patients
      achieving $50% reduction in PGTC seizure frequency; maintenance vs baseline).
      Treatment-emergent adverse events were monitored. RESULTS: Of 164 randomized
      patients, 162 comprised the full analysis set (placebo, 81; perampanel, 81).
      Compared with placebo, perampanel conferred a greater median percent change in
      PGTC seizure frequency per 28 days (238.4%vs 276.5%; p , 0.0001) and greater
      50%PGTC seizure responder rate (39.5% vs 64.2%; p 5 0.0019). During maintenance,
      12.3% of placebo treated patients and 30.9%of perampanel-treated patients
      achieved PGTC seizure freedom. For the safety analysis (placebo, 82; perampanel,
      81), the most frequent treatment-emergent adverse events with perampanel were
      dizziness (32.1%) and fatigue (14.8%). CONCLUSIONS: Adjunctive perampanel was
      well tolerated and improved control of drug-resistant PGTC seizures in patients
      with IGE. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that
      adjunctive perampanel reduces PGTC seizure frequency, compared with placebo, in
      patients with drug-resistant PGTC seizures in IGE.

PMID- 26296513
TI  - Cerebral microbleeds and tissue  plasminogen activator  Does blood beget blood?

PMID- 26296514
TI  - Clinical relevance of voltage-gated  potassium channel-complex antibodies  in
      children.
AB  - OBJECTIVE: To assess the clinical and immunologic findings in children with
      voltage-gated potassium channel (VGKC)-complex antibodies (Abs). METHODS: Thirty
      nine of 363 sera, referred from 2 pediatric centers from 2007 to 2013, had been
      reported positive (.100 pM) for VGKC-complex Abs. Medical records were reviewed
      retrospectively and the patients' condition was independently classified as
      inflammatory (n 5 159) or noninflammatory (n 5 204). Positive sera (.100 pM) were
      tested/retested for the VGKC complex Ab-positive complex proteins LGI1 and
      CASPR2, screened for binding to live hippocampal neurons, and 12 high-titer sera
      (.400 pM) tested by radioimmunoassay for binding to VGKC Kv1 subunits with or
      without intracellular postsynaptic density proteins. RESULTS: VGKC-complex Abs
      were found in 39 children, including 20% of encephalopathies and 7.6% of other
      conditions (p 5 0.001). Thirty children had inflammatory conditions and 9 had
      noninflammatory etiologies but titers.400 pM (n512) were found only in
      inflammatory diseases (p , 0.0001). Four sera, including from 2 children with
      coexisting NMDA receptor Abs and one with Guillain-Barre syndrome and Abs to both
      LGI1 and CASPR2, bound to hippocampal neurons. None of the sera bound detectably
      to VGKC Kv1 subunits on live HEK cells, but 4 of 12 .400 pM sera
      immunoprecipitated VGKC Kv1 subunits, with or without postsynaptic densities,
      extracted from transfected cells. CONCLUSION: Positive VGKC-complex Abs cannot be
      taken to indicate a specific clinical syndrome in children, but appear to be a
      nonspecific biomarker of inflammatory neurologic diseases, particularly of
      encephalopathy. Some of the Abs may bind to intracellular epitopes on the VGKC
      subunits, or to the intracellular interacting proteins, but in many the targets
      remain undefined.

PMID- 26296515
TI  - Salbutamol and ephedrine in the treatment  of severe AChR deficiency syndromes.
AB  - OBJECTIVE: To evaluate the response to salbutamol and ephedrine in the treatment
      of congenital myasthenic syndromes due to CHRNE mutations causing severe
      acetylcholine receptor (AChR)deficiency. METHODS: A cohort study of 6 patients
      with severe AChR deficiency, symptomatic despite optimal therapy with
      anticholinesterase and 3,4-diaminopyridine, were analyzed for their response to
      the addition of salbutamol or ephedrine to their medication. Baseline
      quantitative myasthenia gravis (QMG) (severity) scores were worse than 15 of 39.
      Patients were assessed in clinic with QMG and mobility scores. Pretreatment and 6
      to 8-month follow-up scores were evaluated. RESULTS: All 6 patients tolerated
      treatment well and reported no side effects. There was a strong positive response
      to treatment over the 6- to 8-month assessment period with significant
      improvement in QMG (p = 0.027) and mobility scores. The analysis of subcomponents
      of the QMG score revealed marked improvement in upper (p = 0.028) and lower (p =
      0.028) limb raise times. All patients reported enhanced activities of daily
      living at 6 to 8 months. CONCLUSIONS: Oral salbutamol and ephedrine appear to be
      effective treatments in severe cases ofAChR deficiency on pyridostigmine. They
      are well tolerated and improvement in strength can be dramatic. Classification of
      evidence: This study provides Class IV evidence that salbutamol or ephedrine
      improves muscle strength in patients with congenital myasthenia from severe AChR
      deficiency.

PMID- 26296516
TI  - Suicide risk in patients with migraine and  comorbid fibromyalgia.
AB  - OBJECTIVES: To identify the frequency, clinical effects, and suicide risk in
      comorbid fibromyalgia(FM) among patients with migraine. METHODS: We surveyed
      patients with migraine who attended a headache clinic. All patients completed
      questionnaires containing demographics, headache profiles based on the
      International Classification of Headache Disorders, 2nd edition, FM
      questionnaires based on the modified 2010 American College of Rheumatology
      preliminary diagnostic criteria, Migraine Disability Assessment, Hospital Anxiety
      and Depression Scale, and Pittsburgh Sleep Quality Index. Suicide risk was
      evaluated by self-report of lifetime suicidal ideation and attempts. RESULTS: Of
      the 1,318 recruited patients with migraine (aged 42.6 +/- 12.7 years; female/male
      = 4.5), 10.1% (aged 44.3 +/- 12.6 years; female/male = 7.9) had comorbidity of
      FM. Patients with migraine and comorbid FM had higher headache frequency and
      headache-related disability, poor sleep quality, and were more depressed/anxious
      than those with migraine only (p < 0.001). Suicidal ideation and attempts were
      reported in 27.3% and 6.9% of patients with migraine, respectively, and were
      higher in patients with comorbid FM than in those without (ideation: 58.3% vs
      24%; attempt: 17.6% vs 5.7%; p < 0.001). In addition, comorbidity of FM was
      associated with a higher suicide risk in 3 different migraine subgroups, i.e.,
      migraine without aura, migraine with aura, and chronic migraine. After
      controlling for covariates, comorbidity of FM remained as a predictor of suicidal
      ideation and attempts (odds ratio 2.61 and 1.99, respectively, p < 0.05)in
      patients with migraine. CONCLUSIONS: Comorbidity with FM is associated with a
      high suicide risk in patients with migraine.

PMID- 26296518
TI  - Recurrent vascular events in lacunar stroke  patients with metabolic syndrome
      and/or  diabetes.
AB  - OBJECTIVES: We used a prospective clinical trial to examine the risks conferred
      by metabolic syndrome (METS) and diabetes mellitus (DM) to recurrent strokes in
      the Secondary Prevention of Small Subcortical Strokes (SPS3) study cohort.
      METHODS: The SPS3 trial enrolled 3,020 patients with lacunar strokes.
      Participants were stratified into groups of METS only, DM only, both, or neither
      using American Heart Association/National Heart, Lung, and Blood Institute and
      World Health Organization guidelines. Annualized event rates of strokes,
      myocardial infarction (MI), and all-cause mortality were calculated, and hazard
      ratios (HRs) referencing the "neither" group were computed, controlling for
      significantly associated baseline characteristics. RESULTS: Among 2,999
      participants, 25% had METS only, 6% had DM only, 32% had both conditions, and
      37%had neither. Over a median of 3.8 years of follow-up, there were 274 recurrent
      strokes (240 ischemic, 34 hemorrhagic) and 74 MIs; among the 240 ischemic
      strokes, 134 (56%) were lacunar. The rates of any recurrent stroke (HR 1.7, 95%
      confidence interval [CI] 1.3-2.3) or lacunar stroke (HR 2.4, 95% CI 1.5-3.7) were
      significantly higher for those with concurrent METS and DM compared with those
      who had neither. Risk of incident MI was higher in participants with DM (HR 2.8,
      95% CI 1.1-7.0) or concurrent DM and METS (HR 2.6, 95% CI 1.4-4.9). CONCLUSION:
      METS and DM were significant comorbid conditions in lacunar stroke patients and
      they were associated with stroke recurrence. In patients with lacunar infarcts, a
      vigilant approach to prevent development of DM in those with METS may be a
      potential strategy to reduce recurrent strokes.

PMID- 26296517
TI  - New-onset refractory status epilepticus: Etiology, clinical features, and
      outcome.
AB  - OBJECTIVES: The aims of this study were to determine the etiology, clinical
      features, and predictors of outcome of new-onset refractory status epilepticus.
      METHODS: Retrospective review of patients with refractory status epilepticus
      without etiology identified within 48 hours of admission between January 1, 2008,
      and December 31, 2013, in 13 academic medical centers. The primary outcome
      measure was poor functional outcome at discharge (defined as a score >3 on the
      modified Rankin Scale). RESULTS: Of 130 cases, 67 (52%) remained cryptogenic. The
      most common identified etiologies were autoimmune (19%) and paraneoplastic (18%)
      encephalitis. Full data were available in 125 cases (62 cryptogenic). Poor
      outcome occurred in 77 of 125 cases (62%), and 28 (22%) died. Predictors of poor
      outcome included duration of status epilepticus, use of anesthetics, and medical
      complications. Among the 63 patients with available follow-up data (median 9
      months), functional status improved in 36 (57%); 79% had good or fair outcome at
      last follow-up, but epilepsy developed in 37% with most survivors (92%) remaining
      on antiseizure medications. Immune therapies were used less frequently in
      cryptogenic cases, despite a comparable prevalence of inflammatory CSF changes.
      CONCLUSIONS: Autoimmune encephalitis is the most commonly identified cause of new
      onset refractory status epilepticus, but half remain cryptogenic. Outcome at
      discharge is poor but improves during follow-up. Epilepsy develops in most cases.
      The role of anesthetics and immune therapies warrants further investigation.

PMID- 26296519
TI  - Cerebral microbleeds and  postthrombolysis intracerebral  hemorrhage risk 
      Updated meta-analysis.
AB  - OBJECTIVE: We performed a systematic review and meta-analysis to assess whether
      the presence of cerebral microbleeds (CMBs) on pretreatment MRI scans of patients
      with acute ischemic stroke treated with thrombolysis is associated with an
      increased risk of symptomatic intracerebral hemorrhage (ICH). METHODS: We
      searched PubMed for relevant studies and calculated pooled odds ratios (ORs) for
      symptomatic ICH, using the Mantel-Haenszel fixed-effects method, among
      individuals with vs without CMBs on pretreatment MRI scans. To minimize potential
      bias, sensitivity analysis was performed including studies providing data on
      patients treated only with IV thrombolysis. RESULTS: Ten eligible studies
      including 2,028 patients were pooled in meta-analysis. The overall prevalence of
      CMBs was 23.3%. Among patients with CMBs, 40 of 472 (8.5%; 95%confidence interval
      [CI]: 6.1%-11.4%) experienced a symptomatic ICH after thrombolysis compared with
      61 of 1,556 patients (3.9%; 95% CI: 3%-5%) without CMBs. The pooled OR of ICH
      across all studies was 2.26 (95%CI: 1.46-3.49; p , 0.0001). Eight studies,
      including 1,704 patients (n 5 401 with CMBs), provided data on patients treated
      with IV thrombolysis only; OR for the presence of CMBs and the development of
      symptomatic ICH was 2.87 (95%CI: 1.76-4.69; p , 0.0001). CONCLUSIONS: Our meta
      analysis of the available published data demonstrates an increased risk of
      symptomatic ICH after thrombolysis for acute ischemic stroke in patients with
      CMBs. However, we cannot fully exclude bias or confounding, so our results should
      be considered hypothesis generating. Detecting CMBs should not prevent
      thrombolytic treatment based on present evidence. Further analyses, taking into
      account CMB number and location, as well as measures of functional outcome, are
      needed.

PMID- 26296520
TI  - Association Between Genetic Variants of Akt1 and Endometrial Cancer.
AB  - Akt isoforms have critical roles in the cause and regulation of cancer cells
      invasive, migration, and metastatic dissemination. In the present study, the
      association between Akt1 polymorphisms and endometrial cancer was investigated in
      patients with endometrial cancer and controls. Thirty premenopaused patients
      diagnosed with endometrial cancer and 30 premenopaused women with no clinically
      documented abnormalities of the endometrium undergoing hysterectomy were included
      in this study. Genotypes were determined by polymerase chain reaction and
      restriction fragment length polymorphism. There was no significant difference
      between Akt1 gene polymorphisms of patients (SNP1, SNP2 and SNP3) with
      endometrial cancer and controls (p > 0.05). Difference between alleles frequency
      of SNP1, SNP2, SNP3 of patients with endometrial cancer and controls was not
      significant (p > 0.05). SNPs (rs72715985), (rs2494750), and (rs74090038) of Akt1
      gene are not associated with endometrial cancer in Iranian subjects. 

PMID- 26296522
TI  - Effect of seminal plasma vesicular structures in canine frozen-thawed semen.
AB  - Membrane vesicles (MVs) in the ejaculate have been identified in various species
      and are considered to affect membrane fluidity due to their characteristic
      molecular composition. Addition of MV to human frozen semen has been shown to
      improve post-thaw motility. Similarly, a beneficial effect has been suggested for
      frozen equine semen. As post-thaw canine semen quality varies widely between
      dogs, the aim of our study was to test for the effect of addition of canine MV on
      post-thaw semen quality in dogs. Semen samples from 10 male dogs were purified
      from MV and prepared for freezing. In experiment 1, three groups were compared:
      sperm frozen (1) with MV (S1); (2) without MV, but MV added immediately after
      thawing (S2); and (3) without MV (C). Semen analysis included computer-assisted
      sperm analysis of motility parameters immediately after thawing (t0), after 10
      (t10) and 30 minutes (t30), % living sperm, % membrane intact, % morphologically
      normal sperm (all t0 and t30). Computer-assisted sperm analysis motility distance
      and velocity parameters (all P < 0.05) and % living sperm (P < 0.001) were
      significantly affected by treatment with a temporary increase of distance and
      velocity parameters at t0 to t10, but a significant decrease of the
      aforementioned parameters at t30 in samples with MV. In experiment 2, different
      MV protein concentrations added after thawing were compared: 0.05 mg, 0.1 mg, and
      0.2 mg/mL. Computer-assisted sperm motility analysis was performed at t0, t10,
      and t30. No differences between MV concentrations were identified, only a
      significant interaction between effect of treatment and time for progressive
      motility (P < 0.01). Our study identified a short-term beneficial effect of
      canine MV on post-thaw distance and velocity parameters, whereas at t30
      progressive motility, motility parameters and % living sperm were reduced in
      samples with MV compared to C. The results point to species-specific differences
      regarding the MV effect on frozen semen and indicate the need for further studies
      using different semen and MV purification protocols and more frequent analyses.
      At the moment, addition of MV is not an option to improve post-thaw semen quality
      in dogs. 

PMID- 26296523
TI  - Use of combinations of in vitro quality assessments to predict fertility of
      bovine semen.
AB  - Predicting in vivo fertility of bull ejaculates using in vitro-assessed semen
      quality criteria remains challenging for the breeding industry. New technologies
      such as computer-assisted semen analysis (CASA) and flow cytometry may provide
      accurate and objective methods to improve semen quality control. The aim of this
      study was to evaluate the relationship between semen quality parameters and field
      fertility of bull ejaculates. A total of 153 ejaculates from 19 Holstein bulls
      have been analyzed using CASA (postthawing semen motility and morphology) and
      several flow cytometric tests, including sperm DNA integrity, viability
      (estimated by membrane integrity), acrosomal integrity, mitochondria aerobic
      functionality and oxidation. Samples were analyzed both immediately after thawing
      and after 4 hours at 37  degrees C. A fertility value (FV), based on nonreturn
      rate at 56 days after insemination and adjusted for environment factors, was
      calculated for each ejaculate. Simple and multiple regressions have been used to
      correlate FV with CASA and flow cytometric parameters. Significant simple
      correlations have been observed between some parameters and FV (e.g., straight
      line velocity [MUm/s], r(2) = -0.12; polarized mitochondria sperm (%), r(2) =
      0.07), but the relation between simple parameter and FV was too week to predict
      the fertility. Partial least square procedure identified several mathematical
      models combining flow cytometer and CASA variables and had better correlations
      with FV (adjusted r(2) ranging between 0.24 and 0.40 [P < 0.0001], depending on
      the number of included variables). In conclusion, this study suggests that
      quality assessment of thawed bull sperm using CASA and flow cytometry may provide
      a reasonable prediction of bovine semen fertility. Additional work will be
      required to increase the prediction reliability and promote this technology in
      routine artificial insemination laboratory practice. 

PMID- 26296521
TI  - Substance use, mental illness, and familial conflict non-negotiation among HIV
      positive African-Americans: latent class regression and a new syndemic framework.
AB  - We evaluated a synergistic epidemic (syndemic) of substance use, mental illness,
      and familial conflict non-negotiation among HIV-positive injection drug users
      (IDU). Baseline BEACON study data was utilized. Latent class analyses identified
      syndemic classes. These classes were regressed on sex, viral suppression, and
      acute care non-utilization. Females were hypothesized to have higher syndemic
      burden, and worse health outcomes than males. Nine percent of participants had
      high substance use/mental illness prevalence (Class 4); 23 % had moderate levels
      of all factors (Class 3); 25 % had high mental illness (Class 2); 43 % had
      moderate substance use/mental illness (Class 1; N = 331). Compared to Classes 1
      3, Class 4 was mostly female (p < .05), less likely to achieve viral suppression,
      and more likely to utilize acute care (p < .05). Interventions should target
      African-American IDU females to improve their risk of negative medical outcomes.
      Findings support comprehensive syndemic approaches to HIV interventions, rather
      than singular treatment methods.

PMID- 26296524
TI  - GnRH and its receptor (GnRH-R) are expressed in the canine placenta and uterus.
AB  - In reproductive tissues, GnRH participates in the regulation of cell growth and
      proliferation by direct binding to the GnRH-R, which is essential for embryo
      implantation. However, there is no study on the expression and cellular
      localization of GnRH and GnRH-R in the canine uterus and placenta. Therefore,
      bitches were ovariohysterectomized 10 to 12 days after mating (vaginal cytology
      and progesterone measurement), the uteri were flushed, and if embryos were
      detectable, bitches were allocated to the embryo positive group (E-pos.;
      preimplantation, n = 5). Other bitches were operated at later stages and,
      dependent on the gestational age, either allotted to the post-implantation group
      (Day 18-25 after mating, n = 9), or the mid-gestation group (Day 30-40 after
      mating, n = 3). Dogs negative in embryo flushing served as controls (E-neg.;
      controls, n = 5). Samples of the entire uterine wall were taken from the middle
      of the horn in E-neg. and E-pos. groups, and from placental and interplacental
      uterine sites in post-implantation and mid-gestation groups. GnRH-R expression
      was localized at the mRNA and protein levels by immunohistochemistry and in situ
      hybridization. The expression of GnRH and GnRH-R mRNA was assessed by
      semiquantitative polymerase chain reaction. Additionally, both GnRH and GnRH-R
      mRNA were expressed in all tissues examined until mid-gestation. Relative
      expression of GnRH was higher than that of GnRH-R (P < 0.05). During the post
      implantation stage, GnRH-R expression was significantly higher in uteroplacental
      than in interplacental tissues. In the uterus, GnRH-R stained strongly in the
      surface and glandular epithelial cells, and seemed to be weaker in myometrium and
      stroma. Placental signals were predominantly localized in fetal trophoblast cells
      and to a lesser extent in maternal decidual cells. These findings suggest a local
      regulatory function of GnRH during early canine pregnancy. 

PMID- 26296525
TI  - Effects of short-term exposure of mature oocytes to sodium nitroprusside on in
      vitro embryo production and gene expression in bovine.
AB  - Stress tolerance can be induced in embryos by oocyte exposure to hydrostatic
      pressure, osmotic agents, heat shock, or reactive oxygen species. This study
      assessed the effects of exposing bovine oocytes to a nitric oxide (NO) donor,
      sodium nitroprusside (SNP), on subsequent in vitro embryo production, embryo
      quality and the expression of genes involved in NO production (iNOS, eNOS, and
      nNOS), stress tolerance (HSP70 and HSP90), oxidative stress (HIF1A and PRDX5),
      and apoptosis (BCL2A1). In vitro mature oocytes were incubated with SNP (control,
      10(-6) M, 10(-5) M, and 10(-4) M) for 1 hour before in vitro fertilization, and
      cultured until Day 7. Cleavage and blastocyst rates were recorded. Next, embryo
      quality (ratio of inner cell mass to total cell number) and relative gene
      expression of iNOS, eNOS, nNOS, HSP70, HSP90, HIF1A, PRDX5, and BCL2A1 were
      determined in expanded blastocysts. Cleavage rates were significantly lower for
      10(-4) M SNP compared with the control and 10(-5) M SNP treatments (77 +/- 7.1%,
      82 +/- 8.4%, and 84.9 +/- 4.1%, respectively). Total blastocyst rates were lower
      in the 10(-4) M SNP group relative to the control group (26.2 +/- 4.9% and 34.1
      +/- 7.8%, respectively). Embryo quality was similar among the groups. However,
      our relative gene expression analysis revealed the downregulation of endothelial
      oxide nitric synthase messenger RNA in expanded blastocysts in all the treatment
      groups compared with the control treatment. These results suggest that the short
      term exposure of mature bovine oocytes to a NO donor does not induce their stress
      tolerance and has no beneficial effect on the in vitro embryo production of
      bovine embryos.

PMID- 26296526
TI  - Comparison of dopamine kinetics in the larval Drosophila ventral nerve cord and
      protocerebrum with improved optogenetic stimulation.
AB  - Dopamine release and uptake have been studied in the Drosophila larval ventral
      nerve cord (VNC) using optogenetics to stimulate endogenous release. However,
      other areas of the central nervous system remain uncharacterized. Here, we
      compare dopamine release in the VNC and protocerebrum of larval Drosophila.
      Stimulations were performed with CsChrimson, a new, improved, red light-activated
      channelrhodopsin. In both regions, dopamine release was observed after only a
      single, 4 ms duration light pulse. Michaelis-Menten modeling was used to
      understand release and uptake parameters for dopamine. The amount of dopamine
      released ([DA]p ) on the first stimulation pulse is higher than the average [DA]p
      released from subsequent pulses. The initial and average amount of dopamine
      released per stimulation pulse is smaller in the protocerebrum than in the VNC.
      The average Vmax of 0.08 MUM/s in the protocerebrum was significantly higher than
      the Vmax of 0.05 MUM/s in the VNC. The average Km of 0.11 MUM in the
      protocerebrum was not significantly different from the Km of 0.10 MUM in the VNC.
      When the competitive dopamine transporter (DAT) inhibitor nisoxetine was applied,
      the Km increased significantly in both regions while Vmax stayed the same. This
      work demonstrates regional differences in dopamine release and uptake kinetics,
      indicating important variation in the amount of dopamine available for
      neurotransmission and neuromodulation. We use a new optogenetic tool, red light
      activated CsChrimson, to stimulate the release of dopamine in the ventral nerve
      cord and medial protocerebrum of the larval Drosophila central nervous system. We
      monitored extracellular dopamine by fast scan cyclic voltammetry and used
      Michaelis-Menten modeling to probe the regulation of extracellular dopamine,
      discovering important similarities and differences in these two regions.

PMID- 26296527
TI  - Dermal fibroblast expression of stromal cell-derived factor-1 (SDF-1) promotes
      epidermal keratinocyte proliferation in normal and diseased skin.
AB  - Stromal cells provide a crucial microenvironment for overlying epithelium. Here
      we investigated the expression and function of a stromal cell-specific protein,
      stromal cell-derived factor-1 (SDF-1), in normal human skin and in the tissues of
      diseased skin. Immunohistology and laser capture microdissection (LCM)-coupled
      quantitative real-time RT-PCR revealed that SDF-1 is constitutively and
      predominantly expressed in dermal stromal cells in normal human skin in vivo. To
      our surprise, an extremely high level of SDF-1 transcription was observed in the
      dermis of normal human skin in vivo, evidenced by much higher mRNA expression
      level than type I collagen, the most abundant and highly expressed protein in
      human skin. SDF-1 was also upregulated in the tissues of many human skin
      disorders including psoriasis, basal cell carcinoma (BCC), and squamous cell
      carcinoma (SCC). Double immunostaining for SDF-1 and HSP47 (heat shock protein
      47), a marker of fibroblasts, revealed that fibroblasts were the major source of
      stroma-cell-derived SDF-1 in both normal and diseased skin. Functionally, SDF-1
      activates the ERK (extracellular-signal-regulated kinases) pathway and functions
      as a mitogen to stimulate epidermal keratinocyte proliferation. Both
      overexpression of SDF-1 in dermal fibroblasts and treatment with rhSDF-1 to the
      skin equivalent cultures significantly increased the number of keratinocyte
      layers and epidermal thickness. Conversely, the stimulative function of SDF-1 on
      keratinocyte proliferation was nearly completely eliminated by interfering with
      CXCR4, a specific receptor of SDF-1, or by knock-down of SDF-1 in fibroblasts.
      Our data reveal that extremely high levels of SDF-1 provide a crucial
      microenvironment for epidermal keratinocyte proliferation in both physiologic and
      pathologic skin conditions. 

PMID- 26296528
TI  - Effect of androgen deprivation therapy on arterial stiffness and serum lipid
      profile changes in patients with prostate cancer: a prospective study of initial
      6-month follow-up.
AB  - BACKGROUND: To explore arterial stiffness during the administration of androgen
      deprivation therapy (ADT) in patients with prostate cancer (PCa), a new
      indicator, the cardio-ankle vascular index (CAVI), and serum lipid profile
      changes were monitored. METHODS: A prospective study assessed the changes in
      arterial stiffness using the CAVI and clinical laboratory variables among 58 men
      with prostate cancer treated with ADT for 6 months. Furthermore, patients who had
      a high risk of developing arterial stiffness after ADT were investigated.
      RESULTS: The whole cohort had no significant increase in arterial stiffness
      within 6 months after ADT, but 55.2 % of patients had an increased CAVI. Serum
      levels of total cholesterol, high-density-lipoprotein cholesterol (HDL-C), and
      low-density-lipoprotein cholesterol (LDL-C) increased significantly at 1 month
      after the start of ADT and maintained high values thereafter. At baseline, HDL-C
      was lower and LDL-C and LDL-C/HDL-C were higher in the group with than without an
      increased CAVI after 6 months of ADT administration. CONCLUSIONS: Although the
      whole cohort did not show a significant change in arterial stiffness with ADT,
      some patients showed an increased arterial stiffness monitored with the CAVI. The
      balance between LDL-C and HDL-C, or LDL-C/HDL-C, might have an impact on the
      development of arterial stiffness after ADT administration. Thus, clinicians
      might be able to monitor PCa patients who have a high risk of development of
      arterial stiffness after ADT administration by referring to LDL-C/HDL-C levels.

PMID- 26296529
TI  - The effect of extensive intraoperative peritoneal lavage therapy (EIPL) on stage
      III B + C and cytology-positive gastric cancer patients.
AB  - BACKGROUND: The aim of this study was to investigate the effects of extensive
      intraoperative peritoneal lavage (EIPL) therapy on stage III B + C and CY1/P0
      gastric cancer patients after potentially curative surgery. METHODS: The study
      included 37 patients with CY1/P0 and 23 patients with stage III B + C gastric
      cancer who were treated with potentially curative gastrectomy and EIPL therapy
      between March 1995 and May 2013. D2 lymphadenectomy, R0 resection, and EIPL
      therapy were performed for all cases. RESULTS: Multivariate analysis revealed
      that male gender (P = 0.01) and lymph node metastasis (P = 0.03) were independent
      prognostic factors, while positive cytology was not (P = 0.21). There was no
      significant difference in overall survival rates between the CY1/P0 and stage III
      B + C groups (P = 0.93). There was also no significant difference in peritoneal
      recurrence rates, i.e., 13 (35.1%) in the CY1/P0 group and 5 (21.7%) in the stage
      III B + C group (P = 0.39). CONCLUSIONS: EIPL therapy combined with complete
      resection and sufficient (D2) lymphadenectomy could improve the prognosis of
      CY1/P0 gastric cancer and, to a similar extent, that of stage III B + C.

PMID- 26296531
TI  - Utilization of biodiesel by-products for mosquito control.
AB  - The current paper has elaborated the efficient utilization of non-edible oil seed
      cakes (NEOC), by-products of the bio-diesel extraction process to develop a
      herbal and novel mosquitocidal composition against the Aedes aegypti larvae. The
      composition consisted of botanical active ingredients, inerts, burning agents and
      preservatives; where the botanical active ingredients were karanja (Pongamia
      glabra) cake powder and jatropha (Jatropha curcas) cake powder, products left
      after the extraction of oil from karanja and jatropha seed. The percentage
      mortality value recorded for the combination with concentration, karanja cake
      powder (20%) and jatropha cake powder (20%), 1:1 was 96%. The coil formulations
      developed from these biodiesel by-products are of low cost, environmentally
      friendly and are less toxic than the synthetic active ingredients. 

PMID- 26296530
TI  - Ultrasmall Black Phosphorus Quantum Dots: Synthesis and Use as Photothermal
      Agents.
AB  - Black phosphorus quantum dots (BPQDs) were synthesized using a liquid exfoliation
      method that combined probe sonication and bath sonication. With a lateral size of
      approximately 2.6 nm and a thickness of about 1.5 nm, the ultrasmall BPQDs
      exhibited an excellent NIR photothermal performance with a large extinction
      coefficient of 14.8 L g(-1) cm(-1) at 808 nm, a photothermal conversion
      efficiency of 28.4%, as well as good photostability. After PEG conjugation, the
      BPQDs showed enhanced stability in physiological medium, and there was no
      observable toxicity to different types of cells. NIR photoexcitation of the BPQDs
      in the presence of C6 and MCF7 cancer cells led to significant cell death,
      suggesting that the nanoparticles have large potential as photothermal agents.

PMID- 26296532
TI  - Isolation and analysis of polysaccharide showing high hyaluronidase inhibitory
      activity in Nostochopsis lobatus MAC0804NAN.
AB  - An active substance with high hyaluronidase inhibitory effect was isolated from
      the edible cyanobacterium Nostochopsis lobatus MAC0804NAN strain and
      characterized. The active component in the hot water extract was purified by
      anion exchange and gel filtration chromatography and was found to be a
      polysaccharide. The IC(50) against hyaluronidase of the purified polysaccharide
      was 7.18 MUg/ml whose inhibitory activity is 14.5 times stronger than that of
      disodium cromoglycate (DSCG), an anti-allergy medication. The carbohydrate
      composition which was analyzed by GC-MS and NMR was found to be composed mainly
      of glucose, glucuronic acid, fucose, 2-O-methylfucose, mannose, galactose and
      xylose.

PMID- 26296533
TI  - Blocking the L-type Ca2+ channel (Cav 1.2) is the key mechanism for the vascular
      relaxing effect of Pterodon spp. and its isolated diterpene methyl-6alpha-acetoxy
      7beta-hydroxyvouacapan-17beta-oate.
AB  - Pterodon spp. Vogel (Fabaceae), popularly known as "sucupira", has
      ethnopharmacological application which is described as having antispasmodic and
      relaxant effects. Hence, it was hypothesized that sucupira oil-resin (SOR) could
      induce smooth muscle relaxation. So, this study investigated the mechanisms
      involved in the vasorelaxant effect of SOR and its isolated diterpene (methyl
      6alpha-acetoxy-7beta-hydroxyvouacapan-17beta-oate). Vascular reactivity
      experiments were performed using rat aortic rings (n=5-8) with (E+) or without
      endothelium (E-) in an isolated bath organ. The SOR (0-56 MUg/mL) relaxed
      phenylephrine (E+: 86.7+/-7.1%; E-: 92.3+/-4.7%) and KCl contracted rings (E-:
      97.1+/-2.8%). In the same way, diterpene (0-48 MUg/mL) also relaxed phenylephrine
      (E+: 94.5+/-3.6%; E-: 92.2+/-3.4%) and KCl contracted rings (E-: 99.7+/-0.2%).
      The pre-incubation of arterial rings with cyclopiazonic acid (reticular Ca2+
      ATPase inhibitor), tetraethylammonium (K+ channels blocker) or MDL-12,330A
      (adenylyl cyclesinhibitor) did not modify either SOR- or diterpeneinduced
      vasorelaxation. However, ODQ (guanylyl cyclase inhibitor) impaired only diterpene
      induced vasorelaxation. SOR and diterpene significantly reduced CaCl2-induced
      contraction stimulated by Bay K8644 (1 MUM), phenylephrine (0.1 MUM) or KCl
      solution (40 mM). Computational molecular docking studies demonstrated that the
      vasodilator effect of diterpene relies on blocking the Cav 1.2 channel, and patch
      clamp results showed that diterpene substantially decreased the ionic current
      through Cav 1.2 in freshly dissociated vascular smooth muscle cells. These
      findings suggest that SOR and its isolated diterpene induce endothelium
      independent vascular relaxation by blocking the L-type Ca2+ channel (Cav 1.2).

PMID- 26296534
TI  - Cuffed versus uncuffed endotracheal tubes in children: a meta-analysis.
AB  - PURPOSE: Cuffed endotracheal tubes (ETTs) have increasingly been used in small
      children. However, the use of cuffed ETTs in small children is still
      controversial. The goal of this meta-analysis is to assess the current evidence
      regarding the postextubation morbidity and tracheal tube (TT) exchange rate of
      cuffed ETTs compared to uncuffed ETTs in children. METHODS: A systematic
      literature search in PubMed, Web of Science, Embase, and Cochrane Central
      Register of Controlled Trials up to November 2014 was conducted to identify
      randomized controlled trials (RCTs) and prospective cohort studies that compared
      the use of cuffed and uncuffed ETTs in children. The primary outcome was the
      incidence of postextubation stridor and the second outcomes were the TT exchange
      rate, need for re-intubation, and duration of tracheal intubation. All pooled
      data were estimated using random effects meta-analysis. RESULTS: Two RCTs and two
      prospective cohort studies including 3782 patients, in which 1979 patients for
      cuffed tubes and 1803 patients for uncuffed tubes, were included in our analysis.
      We found that the use of cuffed ETTs did not significantly increase the incidence
      of postextubation stridor (RR = 0.88; 95 % CI 0.67-1.16, p = 0.36), and the TT
      exchange rate was lower in patients receiving cuffed tubes intubation (RR, 0.07;
      95 % CI 0.05-0.10, p < 0.00001). The need for re-intubation following planned
      extubations and duration of tracheal intubation did not differ significantly
      between the cuffed tube group and the uncuffed tube group. CONCLUSIONS: Our study
      demonstrates that cuffed ETTs reduce the need for TT exchanges and do not
      increase the risk for postextubation stridor compared with uncuffed ETTs.

PMID- 26296535
TI  - Qualitative patterns at Raven's colored progressive matrices in mild cognitive
      impairment and Alzheimer's disease.
AB  - BACKGROUND: Visuo-spatial and problem-solving abilities are commonly impaired in
      patients with Alzheimer's disease (AD). Conversely, subjects with amnestic mild
      cognitive impairment (aMCI) do not exhibit overt involvement of cognitive domains
      other than memory. Consequently, a detection of an impairment at the Raven's
      colored progressive matrices (RCPM) could be useful to discriminate aMCI from AD
      and to mark the progression from one condition to another. AIM OF THE STUDY: To
      describe the pattern of errors at RCPM in subjects suffering from AD as compared
      with that of aMCI. METHODS: Fifteen patients with AD, 15 subjects with aMCI and
      31 Healthy Controls (HC) received the RCPM. The errors were classified as: (1)
      difference (D); (2) inadequate individuation (II); (3) repetition of the pattern
      (RP); (4) incomplete correlation (IC). RESULTS: No difference approached
      significance between aMCI subjects and HC. AD patients always exhibited a higher
      number of errors as compared with HC. AD patients showed higher number of errors
      as compared with aMCI only on RP and IC errors. CONCLUSIONS: The results suggest
      that the visuo-spatial and problem-solving impairment that characterize AD, and
      probably subtend the progression from aMCI to dementia, do not affect to the same
      extent all cognitive dimensions explored by RCPM.

PMID- 26296536
TI  - Job satisfaction among 'migrant dentists' in Australia: implications for dentist
      migration and workforce policy.
AB  - BACKGROUND: Migrants occupy a significant proportion of the dental workforce in
      Australia. The objectives of this study were to assess the level of job
      satisfaction of employed migrant dentists in Australia, and to examine the
      association between various migrant dentist characteristics and job satisfaction.
      METHODS: All migrant dentists resident in Australia were surveyed using a five
      point Likert scale that measured specific aspects of job, career and satisfaction
      with area and type of practice. RESULTS: A total of 1022 migrant dentists
      responded to this study; 974 (95.4%) were employed. Responses for all scales were
      skewed towards strongly agree (scores >=4). The overall scale varied by age
      group, marital status, years since arrival to Australia and specialist
      qualification (chi-square, p < 0.05). In a multivariate logistic regression
      model, there was a trend towards greater satisfaction amongst older age groups.
      Dentists who migrated through the examination pathway (mainly from low- and
      middle-income countries) had a lower probability of being satisfied with the area
      and type of practice (OR = 0.71; 0.51-0.98), compared with direct-entry migrant
      dentists (from high-income countries). CONCLUSIONS: The high level of job
      satisfaction of migrant dentists reflects well on their work-related experiences
      in Australia. The study offers policy suggestions towards support for younger
      dentists and examination pathway migrants, so they have appropriate skills and
      standards to fit the Australian health care environment.

PMID- 26296537
TI  - Enhanced 2,3-butanediol production from biodiesel-derived glycerol by engineering
      of cofactor regeneration and manipulating carbon flux in Bacillus
      amyloliquefaciens.
AB  - BACKGROUND: Bacillus amyloliquefaciens B10-127 exhibited an excellent ability for
      industrial-scale microbial fermentation of 2,3-butanediol (2,3-BD) from biodiesel
      derived glycerol. However, the accumulation of by-products (acetoin, acetoin,
      lactate and succinate) and the 2,3-BD yield remains prohibitively low for
      commercial production. RESULTS: Several strategies were developed to manipulate
      the carbon flux to 2,3-BD branch in a designed B. amyloliquefaciens. Firstly,
      extra copies of NADH/NAD(+) regeneration system were introduced into B.
      amyloliquefaciens by co-overproduction of glycerol dehydrogenase and acetoin
      reductase, which resulting in improvement of 2,3-BD production and suppression of
      by-products accumulation. Subsequently, the transcriptional regulator ALsR under
      the control of a moderate promoter PbdhA was introduced into B.
      amyloliquefaciens, which increased carbon flux to 2,3-BD branch. Finally, a three
      stage dissolved oxygen control strategy were proposed based on analysis of the
      characteristic of 2,3-BD fermentation, and a two-stage pH control strategy were
      proposed based on different pH preferences of ACR for reduction and oxidation.
      Following these strategies, a high titer (102.3 g/L), yield (0.44 g/g), and
      productivity (1.16 g/L/h) of 2,3-BD were achieved. CONCLUSIONS: To our knowledge,
      this is the highest reported 2,3-BD production using biodiesel-derived glycerol
      as substrate, and this designed B. amyloliquefaciens should be an excellent
      candidate for producing 2,3-BD on an industrial scale.

PMID- 26296538
TI  - Minimally invasive surgery for atrial fibrillation.
AB  - The surgical treatment of atrial fibrillation (AF) has been revolutionized over
      the past two decades through surgical innovation and improvements in endoscopic
      imaging, ablation technology, and surgical instrumentation. These advances have
      prompted the development of the less complex and less morbid Cox-Maze IV
      procedure, and have allowed its adaptation to a minimally invasive right mini
      thoracotomy approach that can be used in stand-alone AF ablation and in patients
      undergoing concomitant mitral and tricuspid valve surgery. Other minimally
      invasive ablation techniques have been developed for stand-alone AF ablation,
      including video-assisted pulmonary vein isolation, extended left atrial lesion
      sets, and a hybrid approach. This review will discuss the tools, techniques, and
      outcomes of minimally invasive surgical procedures currently being practiced for
      AF ablation. 

PMID- 26296539
TI  - A randomized, double-blind, placebo-controlled phase III trial of duloxetine in
      Japanese fibromyalgia patients.
AB  - INTRODUCTION: Fibromyalgia is characterized by widespread pain and is often
      accompanied by accessory symptoms. There are limited treatment options for this
      condition in Japan. Therefore, we conducted a phase III study to assess the
      efficacy and safety of duloxetine in Japanese patients with fibromyalgia.
      METHODS: This randomized, double-blind, placebo-controlled, parallel-group trial
      was conducted in Japan. Outpatients who met the American College of Rheumatology
      1990 criteria for fibromyalgia and whose Brief Pain Inventory (BPI) average pain
      score was >=4 were randomized to duloxetine 60 mg or placebo once daily for 14
      weeks. The primary efficacy measure was the change in the BPI average pain score
      from baseline. Secondary efficacy, quality of life (QoL), and safety outcomes
      were also evaluated. Mixed-effects model repeated-measures (MMRM) analysis and
      last observation carried forward (LOCF) analysis of covariance were used to
      evaluate the primary efficacy measure. RESULTS: Overall, 393 patients were
      randomized to receive either duloxetine (n = 196) or placebo (n = 197). The MMRM
      analysis revealed no significant difference between duloxetine and placebo
      regarding the change in BPI average pain scores at week 14. Based on LOCF
      analysis, a statistically significant improvement in the change in BPI average
      pain scores at week 14 was observed for patients treated with duloxetine compared
      with placebo. Duloxetine treatment was associated with improved outcomes in
      nearly all secondary and post hoc analyses. The treatment was generally well
      tolerated. Somnolence, nausea, and constipation were the most common treatment
      emergent adverse events in the duloxetine group. The discontinuation rates due to
      treatment-emergent adverse events were similar in both groups. CONCLUSIONS:
      Although the MMRM analysis did not demonstrate superiority of duloxetine over
      placebo, duloxetine treatment was associated with improved outcomes in secondary
      and post hoc analyses of the mean change in the BPI average pain score and most
      of the secondary outcomes, including analgesia and QoL. Duloxetine treatment was
      safe and well tolerated. These results suggest that duloxetine treatment could be
      associated with improvements in pain relief and QoL in Japanese patients with
      fibromyalgia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01552057 .
      Registered 9 March 2012.

PMID- 26296540
TI  - Differentiation of deep venous thrombosis from femoral vein mixing artifact on
      routine abdominopelvic CT.
AB  - PURPOSE: The objective of this study is to assess the performance of qualitative
      and quantitative imaging features for the differentiation of deep venous
      thrombosis (DVT) from mixing artifact on routine portal venous phase
      abdominopelvic CT. METHODS: This retrospective study included 40 adult patients
      with a femoral vein filling defect on portal venous phase CT and a Duplex
      ultrasound (n = 36) or catheter venogram (n = 4) to confirm presence or absence
      of DVT. Two radiologists (R1, R2) assessed the femoral veins for various
      qualitative and quantitative features. RESULTS: 60% of patients were confirmed to
      have DVT and 40% had mixing artifact. Features with significantly greater
      frequency in DVT than mixing artifact (all p <= 0.006) were central location (R1
      90% vs. 28%; R2 96% vs. 31%), sharp margin (R1 83% vs. 28%; R2 96% vs. 31%),
      venous expansion (R1 48% vs. 6%, R2 56% vs. 6%), and venous wall enhancement (R1
      62% vs. 0%; R2 48% vs. 0%). DVT exhibited significantly lower mean attenuation
      than mixing artifact (R1 42.1 +/- 20.2 vs. 57.1 +/- 23.6 HU; R2 43.6 +/- 19.4 vs.
      58.8 +/- 23.4 HU, p <= 0.031) and a significantly larger difference in vein
      diameter compared to the contralateral vein (R1 0.4 +/- 0.4 vs. 0.1 +/- 0.2 cm;
      R2 0.3 +/- 0.4 vs. 0.0 +/- 0.1 cm, p <= 0.026). At multivariable analysis,
      central location and sharp margin were significant independent predictors of DVT
      for both readers (p <= 0.013). CONCLUSION: Awareness of these qualitative and
      quantitative imaging features may improve radiologists' confidence for
      differentiating femoral vein DVT and mixing artifact on routine portal venous
      phase CT. However, given overlap with mixing artifact, larger studies remain
      warranted.

PMID- 26296542
TI  - Exploring undergraduate nursing students' perceptions of working in aged care
      settings: A review of the literature.
AB  - OBJECTIVES: To explore undergraduate nursing students' perceptions of working in
      the aged care setting through a review of the literature. DESIGN: A review of
      available literature relating to undergraduate nursing students' attitudes,
      perceptions and experiences in the aged care setting, or in the care of older
      adults. DATA SOURCES: CINAHL Plus with Full Text was the primary database used.
      Other databases include PsycINFO and Health Source: Nursing/Academic Edition.
      REVIEW METHODS: Studies focused on undergraduate nursing students and their
      experiences in the aged care setting and on the perceptions and attitudes of
      nursing students toward older adults, were included. Studies that did not present
      an original study or those that did not meet the aim of the study were excluded
      from the review. RESULTS: Following removal of duplicates and exclusion of
      articles not meeting the aim of this paper, 24 articles remained. Three main
      themes emerged from the review of the literature: perceptions of aged care
      placement, attitudes to working in aged care, and experiences in aged care.
      CONCLUSION: The experiences of nursing students employed as undergraduate AINs in
      the aged care setting can provide an immersive clinical learning experience in
      preparation for their new graduate (NG) year. Furthermore, it is an opportunity
      to challenge ageist attitudes and instil core nursing values in novice nurses
      such as promoting compassionate care.

PMID- 26296543
TI  - A trial of e-simulation of sudden patient deterioration (FIRST2ACT WEB) on
      student learning.
AB  - BACKGROUND: High-fidelity simulation pedagogy is of increasing importance in
      health professional education; however, face-to-face simulation programs are
      resource intensive and impractical to implement across large numbers of students.
      OBJECTIVES: To investigate undergraduate nursing students' theoretical and
      applied learning in response to the e-simulation program-FIRST2ACT WEBTM, and
      explore predictors of virtual clinical performance. DESIGN AND SETTING: Multi
      center trial of FIRST2ACT WEBTM accessible to students in five Australian
      universities and colleges, across 8 campuses. PARTICIPANTS: A population of 489
      final-year nursing students in programs of study leading to license to practice.
      METHODS: Participants proceeded through three phases: (i) pre-simulation-briefing
      and assessment of clinical knowledge and experience; (ii) e-simulation-three
      interactive e-simulation clinical scenarios which included video recordings of
      patients with deteriorating conditions, interactive clinical tasks, pop up
      responses to tasks, and timed performance; and (iii) post-simulation feedback and
      evaluation. Descriptive statistics were followed by bivariate analysis to detect
      any associations, which were further tested using standard regression analysis.
      RESULTS: Of 409 students who commenced the program (83% response rate), 367
      undergraduate nursing students completed the web-based program in its entirety,
      yielding a completion rate of 89.7%; 38.1% of students achieved passing clinical
      performance across three scenarios, and the proportion achieving passing clinical
      knowledge increased from 78.15% pre-simulation to 91.6% post-simulation.
      Knowledge was the main independent predictor of clinical performance in
      responding to a virtual deteriorating patient R(2)=0.090, F(7, 352)=4.962,
      p<0.001. DISCUSSION: The use of web-based technology allows simulation activities
      to be accessible to a large number of participants and completion rates indicate
      that 'Net Generation' nursing students were highly engaged with this mode of
      learning. CONCLUSION: The web-based e-simulation program FIRST2ACTTM effectively
      enhanced knowledge, virtual clinical performance, and self-assessed knowledge,
      skills, confidence, and competence in final-year nursing students.

PMID- 26296541
TI  - Contact-facilitated drug delivery with Sn2 lipase labile prodrugs optimize
      targeted lipid nanoparticle drug delivery.
AB  - Sn2 lipase labile phospholipid prodrugs in conjunction with contact-facilitated
      drug delivery offer an important advancement in Nanomedicine. Many drugs
      incorporated into nanosystems, targeted or not, are substantially lost during
      circulation to the target. However, favorably altering the pharmacokinetics and
      volume of distribution of systemic drug delivery can offer greater efficacy with
      lower toxicity, leading to new prolonged-release nanoexcipients. However, the
      concept of achieving Paul Erhlich's inspired vision of a 'magic bullet' to treat
      disease has been largely unrealized due to unstable nanomedicines, nanosystems
      achieving low drug delivery to target cells, poor intracellular bioavailability
      of endocytosed nanoparticle payloads, and the substantial biological barriers of
      extravascular particle penetration into pathological sites. As shown here, Sn2
      phospholipid prodrugs in conjunction with contact-facilitated drug delivery
      prevent premature drug diffusional loss during circulation and increase target
      cell bioavailability. The Sn2 phospholipid prodrug approach applies equally well
      for vascular constrained lipid-encapsulated particles and micelles the size of
      proteins that penetrate through naturally fenestrated endothelium in the bone
      marrow or thin-walled venules of an inflamed microcirculation. At one time
      Nanomedicine was considered a 'Grail Quest' by its loyal opposition and even many
      in the field adsorbing the pains of a long-learning curve about human biology and
      particles. However, Nanomedicine with innovations like Sn2 phospholipid prodrugs
      has finally made 'made the turn' toward meaningful translational success.

PMID- 26296544
TI  - Validation of the Australian Nursing Standards Assessment Tool (ANSAT): A pilot
      study.
AB  - BACKGROUND: Workplace-based learning and assessment are essential elements of all
      nursing education programs. There is, however, limited evidence of validity and
      reliability available regarding assessment instruments, based on the professional
      competency standards for nursing in Australia. OBJECTIVE: The aims of this
      project were to advance the assessment properties of a new instrument, the
      Australian Nursing Standards Assessment Tool (ANSAT) and investigate the
      acceptability of this instrument when applied to the evaluation of the
      professional competence of nursing students in authentic practice settings.
      METHODS: A validation study of ANSAT was conducted by 23 clinical assessors from
      two universities, completing 220 instruments for second and third year
      undergraduate nursing students undertaking clinical placement in an authentic
      practice setting. 'Think Aloud' interviews and a post-test survey provided
      additional data to determine the validity and acceptability of the ANSAT. The
      pilot study occurred in parallel with completion of existing university
      assessment instruments. RESULTS: Principal components analysis extracted one
      factor: professional practice competence. Comparison of total instrument scores
      between year levels demonstrated a significant difference in each of the clinical
      domains (p=0.000), suggesting that the instrument is sensitive to differing
      levels of performance across different year levels. The ANSAT demonstrated high
      internal consistency with a Cronbach's alpha coefficient of 0.976. Post-test
      evaluation completed by assessors demonstrated high usability and acceptability
      for use in common practice settings. DISCUSSION: Results of the pilot study
      provided preliminary support for the ANSAT instrument. It is recommended that
      testing of the instrument be undertaken on a larger cohort to ensure the
      generalisability of the findings to other nursing populations. CONCLUSION: There
      is a need for valid and reliable instruments that assess the performance of
      nursing in the authentic practice setting. With the addition of supportive
      behavioural cues, the ANSAT enables clarity, consistency and collaboration in
      workplace-based assessment.

PMID- 26296545
TI  - Risk factors for ectopic pregnancy: a multi-center case-control study.
AB  - BACKGROUND: Ectopic pregnancy (EP) is the leading cause of maternal death during
      the first trimester of pregnancy. A better understanding of EP risk can help
      prevent its occurrence. We carried out a multi-center, large-sample, case-control
      study to evaluate the risk factors for EP in Shanghai, China. METHODS: Women who
      were diagnosed with EP (n = 2411) and women with intrauterine pregnancies (n =
      2416) were recruited from five hospitals in Shanghai, China. Information
      regarding the sociodemographic characteristics; reproductive, gynecological and
      surgical history; and previous and current use of contraceptives was collected
      from all participants. Odds ratios (ORs) and 95% confidence intervals (CIs) were
      calculated and adjusted for potential confounding factors via multivariate
      logistic regression analysis. RESULTS: The study revealed that the risk of EP was
      associated with the traditional risk factors including previous EP (Adjusted odds
      ratio [AOR] = 2.72, 95% CI: 1.83-4.05), previous Chlamydia trachomatis infection
      (Adjusted OR = 3.18, 95% CI: 2.64, 3.84), previous infertility (AOR = 2.18, 95%
      CI: 1.66-2.88), previous adnexal surgery (AOR = 2.09, 95% CI: 1.49-2.93),
      previous appendectomy (AOR = 1.64, 95% CI: 1.13-2.37), and previous use of
      intrauterine devices (IUDs) (AOR = 1.72, 95% CI: 1.39-2.13). Additionally, EP
      risk was increased following the failure of most contraceptives used in the
      current cycle including IUDs (AOR = 16.43, 95% CI: 10.42-25.89), oral
      contraceptive pills (AOR = 3.02, 95% CI: 1.16-7.86), levonorgestrel emergency
      contraception (AOR = 4.75, 95% CI: 3.79-5.96), and female sterilization (AOR = 4
      .73, 95% CI: 1.04-21.52). Stratified analysis showed that in vitro fertilization
      and embryo transfer (IVF-ET) was the main risk factor for EP in women with tubal
      infertility (AOR = 8.99, 95% CI: 1.98-40.84), although IVF-ET showed no
      association with EP in women with non-tubal infertility (AOR = 2.52, 95% CI: 0.14
      44.67). CONCLUSION: In addition to the traditional risk factors, IVF-ET and
      current IUD use play dominant roles in the occurrence of EP. Attention should be
      given to women with tubal infertility who have undergone IVE-ET treatment.

PMID- 26296546
TI  - Behavioral Counseling in Primary Care: Perspectives in Enhancing the Evidence
      Base.

PMID- 26296547
TI  - Behavioral Counseling Interventions Expert Forum: Overview and Primer on U.S.
      Preventive Services Task Force Methods.
AB  - The importance of behavioral counseling as a clinical preventive service derives
      from the social and economic burden of preventable disease in the U.S., the
      central role behavioral risk factors play as leading causes of premature
      morbidity and mortality, and the promise of the healthcare visit as a teachable
      moment for behavioral counseling support. In November 2013, the U.S. Preventive
      Services Task Force convened an expert forum on behavioral counseling
      interventions. The forum brought together NIH, CDC, and Agency for Healthcare
      Research and Quality leaders, leading behavioral counseling researchers, and
      members of the U.S. Preventive Services Task Force to discuss issues related to
      optimizing evidence-based behavioral counseling recommendations. This paper
      provides an overview of the methods used by the Task Force to develop counseling
      recommendations. Special focus is on the development and evaluation of evidence
      from systematic reviews. Assessment of the net benefit of a behavioral counseling
      intervention, based on the evidence review, determines the recommendation
      statement and accompanying letter grade. A recent Task Force recommendation on
      screening and behavioral counseling interventions in primary care to reduce
      alcohol misuse provides a brief example. 

PMID- 26296548
TI  - Evaluating Feasible and Referable Behavioral Counseling Interventions.
AB  - The U.S. Preventive Services Task Force (USPTF) recognizes that behaviors have a
      major impact on health and well-being. Currently, the USPSTF has 11 behavioral
      counseling intervention (BCI) recommendations. These BCIs can be delivered in a
      primary care setting or patients can be referred to other clinical or community
      programs. Unfortunately, many recommended BCIs are infrequently and ineffectually
      delivered, suggesting that more evidence is needed to understand which BCIs are
      feasible and referable. In response, the USPSTF convened an expert forum in 2013
      to inform the evaluation of BCI feasibility. This manuscript reports on findings
      from the forum and proposes that researchers use several frameworks to help
      clinicians and the USPSTF evaluate which BCIs work under usual conditions. A key
      recommendation for BCI researchers is to use frameworks whose components can
      support dissemination and implementation efforts. These frameworks include the
      Template for Intervention Description and Replication (TIDieR), which helps
      describe the essential components of an intervention, and pragmatic frameworks
      like Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) or
      Pragmatic-Explanatory Continuum Indicator Summary (PRECIS), which help to report
      study design elements and outcomes. These frameworks can both guide the design of
      more-feasible BCIs and produce clearer feasibility evidence. Critical evidence
      gaps include a better understanding of which patients will benefit from a BCI,
      how flexible interventions can be without compromising effectiveness, required
      clinician expertise, necessary intervention intensity and follow-up, impact of
      patient and clinician intervention adherence, optimal conditions for BCI
      delivery, and how new care models will influence BCI feasibility. 

PMID- 26296549
TI  - Standards of Evidence for Behavioral Counseling Recommendations.
AB  - Behavioral counseling interventions to promote healthy behaviors can
      significantly reduce leading causes of disease and death. Recommendations for
      delivery of these interventions in primary care have been and continue to be an
      important part of the U.S. Preventive Services Task Force's portfolio of clinical
      preventive services recommendations. However, primary and secondary research on
      the effectiveness of behavioral counseling interventions can be more complex than
      recommendations for screening or use of preventive medications. The nature of
      behavior change and interventions to promote it can lead to unique challenges.
      This paper summarizes and expands upon an extensive discussion held at the U.S.
      Preventive Services Task Force's Expert Forum on behavioral counseling
      interventions held in November 2013. The paper describes the foundational
      challenges for using behavioral outcomes as evidence to support a Task Force
      recommendation. The paper discusses research design and reporting characteristics
      needed by behavioral counseling intervention researchers in order for their
      research to contribute to the evidentiary basis of a Task Force recommendation.
      Finally, the paper identifies critical issues that need to be considered by the
      Task Force and other stakeholders to maintain confidence and credibility in the
      standards of evidence for behavioral counseling recommendations. 

PMID- 26296550
TI  - Understanding Research Gaps and Priorities for Improving Behavioral Counseling
      Interventions: Lessons Learned From the U.S. Preventive Services Task Force.
AB  - Behavioral counseling interventions can address significant causes of preventable
      morbidity and mortality. However, despite a growing evidence base for behavioral
      counseling interventions, there remain significant research gaps that limit
      translating the evidence into clinical practice. Using U.S. Preventive Services
      Task Force (USPSTF) examples, we address how researchers and funders can move the
      research portfolio forward to achieve better application of behavioral counseling
      interventions to address substantial health burdens in the U.S. This paper
      describes the types of gaps that the USPSTF encounters across its behavioral
      counseling intervention topics and provides suggestions for opportunities to
      address these gaps to enhance the evidence base for primary care-based behavioral
      counseling recommendations. To accomplish this, we draw from both the USPSTF
      experience and issues identified by researchers and clinicians during the USPSTF
      sponsored Behavioral Counseling Intervention Forum. We also discuss the dilemma
      posed by having "insufficient" evidence with which to make a behavioral
      counseling intervention-related recommendation, and describe two case examples
      (screening for alcohol misuse in adolescence and screening for child
      maltreatment), detailing the research gaps that remain. Recommendations are
      outlined for researchers, funders, and practice implementers to improve
      behavioral counseling intervention research and application. 

PMID- 26296551
TI  - Enhancing Coordination Among the U.S. Preventive Services Task Force, Agency for
      Healthcare Research and Quality, and National Institutes of Health.
AB  - This paper focuses on the relationships among the U.S. Preventive Services Task
      Force (USPSTF); Agency for Healthcare Research and Quality (AHRQ); and NIH. After
      a brief description of the Task Force, AHRQ, NIH, and an example of how they
      interact, we describe the steps that have been taken recently by NIH to enhance
      their coordination. We also discuss several challenges that remain and consider
      potential remedies that NIH, AHRQ, and investigators can take to provide the
      USPSTF with the data it needs to make recommendations, particularly those
      pertaining to behavioral interventions. 

PMID- 26296552
TI  - Aligning the Work of Two U.S. Task Forces on Behavioral Counseling
      Recommendations.
AB  - This paper highlights the collaboration and alignment between topics and
      recommendations related to behavioral counseling interventions from the U.S.
      Preventive Services Task Force (USPSTF) and Community Preventive Services Task
      Force (CPSTF). Although the scope and mandates of the USPSTF and CPSTF differ,
      there are many similarities in the methods and approaches used to select topics
      and make recommendations to their key stakeholders. Behavioral counseling
      recommendations represent an important domain for both Task Forces, given the
      importance of behavior change in promoting healthful lifestyles. This paper
      explores opportunities for greater alignment between the two Task Forces and
      compares and contrasts the groups and their current approaches to making
      recommendations that involve behavioral counseling interventions. Opportunities
      to enhance behavioral counseling preventive services through closer coordination
      when developing and disseminating recommendations as well as future collaboration
      between the USPSTF and CPSTF are discussed. 

PMID- 26296553
TI  - Enhancing the Evidence for Behavioral Counseling: A Perspective From the Society
      of Behavioral Medicine.
AB  - U.S. Preventive Services Task Force (USPSTF) clinical guidelines at present
      rarely assign the highest grade recommendation to behavioral counseling
      interventions for chronic disease prevention or risk reduction because of
      concerns about the certainty and quality of the evidence base. As a result, the
      broad integration of behavioral counseling interventions in primary care remains
      elusive. Thus, there is an urgent need for novel perspectives on how to generate
      the highest-quality and -certainty evidence for primary care-focused behavioral
      counseling interventions. As members of the Society of Behavioral Medicine (SBM)-
      a multidisciplinary scientific organization committed to improving population
      health through behavior change--we review the USPSTF mandate and current
      recommendations for behavioral counseling interventions and provide a perspective
      for the future that calls for concerted and coordinated efforts among SBM,
      USPSTF, and other organizations invested in the rapid and wider uptake of
      beneficial, feasible, and referable primary care-focused behavioral counseling
      interventions. This perspective highlights five areas for further development,
      including (1) behavioral counseling-focused practice-based research networks; (2)
      promotion of USPSTF evidence standards and the increased use of pragmatic RCT
      design; (3) quality control and improvement procedures for behavioral counseling
      training; (4) systematic research on effective primary care-based collaborative
      care models; and (5) methodologic innovations that capitalize on disruptive
      technologies and healthcare transformation. Collective efforts to improve the
      health of all Americans in the 21st century and beyond must ensure that
      effective, feasible, and referable behavioral counseling interventions are
      embedded in modern primary care practice.

PMID- 26296554
TI  - Perspectives in Implementing a Primary Care-Based Intervention to Reduce Alcohol
      Misuse.
AB  - In 2013, the U.S. Preventive Services Task Force (USPSTF) recommended screening
      followed by brief behavioral counseling to reduce alcohol misuse. Our study,
      Options Regarding Consumption of Alcohol (ORCA), was one of the studies included
      in an evidence review that comprised 23 RCTs. ORCA was designed to test whether a
      primary care-based intervention would reduce alcohol misuse among patients who
      screened positive for risky or hazardous drinking. Data collection occurred
      between 1995 and 1999; data analysis was conducted in 2000-2002. Study design and
      implementation built from a behavioral counseling research paradigm with four
      components: (1) population-based screening; (2) centralized delivery of
      intervention components; (3) involvement of primary care practitioners to
      motivate and reinforce behavior change; and (4) personalization of intervention
      components. In this paper, we assess the study features using the Pragmatic
      Explanatory Continuum Indicator Summary Model domains. As a randomized trial, the
      study included some explanatory features (e.g., standardized follow-up surveys
      administered by study personnel); however, several aspects of the study were
      highly pragmatic. Practicable recruitment and training of providers, embedding
      population-based screening in pre-visit surveys, and keeping the delivery of the
      primary care intervention components consistent with the tempo and competing
      priorities of practice are three key features that contributed to the study's
      success and relevance to the USPSTF. 

PMID- 26296555
TI  - Perspectives in Implementing a Pragmatic Pediatric Primary Care-Based
      Intervention Trial.
AB  - The 2013 U.S. Preventive Services Task Force (USPSTF) concluded that behavioral
      interventions are effective in reducing initiation of smoking in youth,
      recommending primary care clinicians provide education or brief counseling to
      prevent initiation, and that there are promising trends toward behavioral
      interventions improving cessation in this population. Our primary care-based
      intervention RCT conducted between 2000 and 2004, Air It Out, informed these
      USPSTF recommendations. Our trial was designed to determine whether a pediatric
      primary care practice-based smoking prevention and cessation intervention would
      be effective in increasing abstinence rates among adolescents under usual clinic
      conditions, to inform clinical practice. Therefore, the trial was designed to be
      largely a pragmatic trial. In this paper, we describe where each of the Air It
      Out study components falls along the pragmatic-explanatory continuum regarding
      participant eligibility criteria, intervention and comparison condition design,
      follow-up and outcomes, compliance and adherence assessments, and analysis. Such
      an assessment assists researchers by providing a framework to guide decisions
      regarding study design and implementation. We then share a few principles and
      lessons learned in developing and implementing the primary care-based
      intervention trial, focusing on study setting selection, engaging providers who
      will be delivering the intervention and the target population who will be
      receiving it in designing the trial and interventions to be tested, and the need
      to carefully plan recruitment and retention procedures. The hope is to increase
      the number of well-designed studies that can be included in the evidence reviews
      to guide future USPSTF recommendation statements. 

PMID- 26296556
TI  - Applying the Pragmatic-Explanatory Continuum Indicator Summary Model in a Primary
      Care-Based Lifestyle Intervention Trial.
AB  - The majority of adults in the U.S. can be classified as overweight or obese
      (68%), putting them at risk for Type 2 diabetes, cardiovascular diseases, and
      other adverse health outcomes. The U.S. Preventive Services Task Force recommends
      that providers offer or refer obese adults to intensive, multicomponent lifestyle
      interventions. However, there is a critical need for interventions that have been
      shown to be pragmatic and effective among diverse populations, scalable across
      different clinical settings and systems, and sustainable over time. The Pragmatic
      Explanatory Continuum Indicator Summary (PRECIS) tool can be used to assess the
      degree to which trials of behavioral lifestyle interventions provide evidence to
      support this need. We used our recently completed trial, Evaluation of Lifestyle
      Interventions to Treat Elevated Cardiometabolic Risk in Primary Care (E-LITE), as
      a case study and assessed the domains of PRECIS to explore the degree to which we
      felt it achieved its intended pragmatic design (completed in December 2014).
      Overall, the systematic assessment using the PRECIS tool revealed that the E-LITE
      trial design was very pragmatic in nature. Its results and the subsequent
      adoption of the intervention into actual practice also suggest high potential for
      implementation of primary care interventions. 

PMID- 26296557
TI  - Improving Health-Related Behaviors: Opportunities and Challenges.

PMID- 26296558
TI  - A cross sectional study between the prevalence of chronic pain and academic
      pressure in adolescents in China (Shanghai).
AB  - BACKGROUND: The purpose of this study was to investigate the prevalence of four
      types of chronic pain (headache, abdominal pain, neck and shoulder pain (NSP),
      and low back pain (LBP)) and to explore the relationship between the prevalence
      of chronic pain and self-reported academic pressure in high school students in
      Shanghai, China. METHOD: Three thousand students were randomly surveyed on
      related issues using a questionnaire, and the results were analyzed using a
      multivariate logistic regression model. RESULTS: Among the 2849 high school
      students who completed the questionnaire, the overall prevalence rates of
      headache, abdominal pain, NSP, and LBP were 30.3, 20.9, 32.8, and 41.1%,
      respectively. The students in general experienced a heavy burden of learning, a
      high level of stress, and sleep deprivation, which were closely related to the
      four types of chronic pain. CONCLUSION: Chronic pain is a common condition in
      Chinese adolescents and is closely related to self-reported academic pressure.

PMID- 26296560
TI  - Usage and perceptions of anabolic-androgenic steroids among male fitness centre
      attendees in Kuwait--a cross-sectional study.
AB  - BACKGROUND: Considering the recent popularity of bodybuilding and the apparent
      spread of anabolic androgenic steroid (AAS) use amongst bodybuilding enthusiasts
      in Kuwait, there is a relative lack of scientific investigation into the use,
      knowledge and attitudes towards AAS amongst the population at risk of abusing it.
      Therefore, this study aims to investigate the frequency, knowledge, attitudes and
      practice of AAS use amongst male fitness centre attendees in Kuwait. METHODS: A
      cross sectional survey utilizing a self-administered questionnaire was used.
      Information on demographics as well as knowledge and attitude about and towards
      the use of AAS was included in the questionnaire. Ten fitness centres in Kuwait
      were randomly selected and questionnaires were distributed to all individuals
      leaving each centre on randomly selected days and periods of time for each
      centre. Overall n = 400 questionnaires were distributed. RESULTS: A total of n =
      194 questionnaires were returned completed (~49%). Of the responders, 22.7% used
      AAS. The 19-25 age group had the highest occurrence (46.8%) of first-time AAS
      use. In contrast with non-users, most (70.5%) of AAS users believed that having
      an optimally muscular body can only be achieved by using AAS, and a small
      minority (6.8%) believed that AAS usage would have significant harms to health.
      Only 18.2% of AAS users had appropriate knowledge regarding the side effects of
      AAS. Non-users were as much uninformed as AAS users regarding the side effects of
      AAS. CONCLUSION: The usage of AAS is high amongst male gym users in Kuwait and is
      likely to present an additional burden to the health service. An effective
      initiative to minimize the burden of AAS abuse should focus on changing the
      attitudes towards AAS rather than spreading awareness of their side effects.

PMID- 26296559
TI  - Stool microbiota composition is associated with the prospective risk of
      Plasmodium falciparum infection.
AB  - BACKGROUND: In humans it is unknown if the composition of the gut microbiota
      alters the risk of Plasmodium falciparum infection or the risk of developing
      febrile malaria once P. falciparum infection is established. Here we collected
      stool samples from a cohort composed of 195 Malian children and adults just prior
      to an intense P. falciparum transmission season. We assayed these samples using
      massively parallel sequencing of the 16S ribosomal RNA gene to identify the
      composition of the gut bacterial communities in these individuals. During the
      ensuing 6-month P. falciparum transmission season we examined the relationship
      between the stool microbiota composition of individuals in this cohort and their
      prospective risk of both P. falciparum infection and febrile malaria. RESULTS:
      Consistent with prior studies, stool microbial diversity in the present cohort
      increased with age, although the overall microbiota profile was distinct from
      cohorts in other regions of Africa, Asia and North America. Age-adjusted Cox
      regression analysis revealed a significant association between microbiota
      composition and the prospective risk of P. falciparum infection; however, no
      relationship was observed between microbiota composition and the risk of
      developing febrile malaria once P. falciparum infection was established.
      CONCLUSIONS: These findings underscore the diversity of gut microbiota across
      geographic regions, and suggest that strategic modulation of gut microbiota
      composition could decrease the risk of P. falciparum infection in malaria-endemic
      areas, potentially as an adjunct to partially effective malaria vaccines.

PMID- 26296561
TI  - Improved identification of people at risk of psychosis: is it value for money?

PMID- 26296563
TI  - Mechanism of immunoglobulin G adsorption on polystyrene microspheres.
AB  - The adsorption of polyclonal immunoglobulin G (IgG) on negatively charged
      polystyrene microparticle suspension (latex) was studied by using the Laser
      Doppler Velocimetry (LDV) measurements. Using this technique, the dependence of
      the electrophoretic mobility of particles on the IgG concentration in the
      suspension was measured for various ionic strengths and pH 3.5. The increase in
      the electrophoretic mobility was quantitatively interpreted in terms of the 3D
      electrokinetic model. On the other hand, the maximum coverage of IgG on latex was
      determined using the depletion method based on AFM imaging. It was shown that IgG
      adsorption was irreversible and that its maximum coverage on the microspheres
      increased from 1.4mgm(-2) for 0.001M NaCl to 2.0mgm(-2) for 0.15M NaCl. This was
      interpreted in terms of reduced electrostatic repulsion among adsorbed molecules.
      The stability of IgG monolayers on the particles was confirmed in separate
      experiments where changes in its electrophoretic mobility were monitored over
      prolonged time periods. Additionally, the acid-base properties of the IgG
      monolayers on latex were determined in pH cycling experiments. The isoelectric
      point of the IgG monolayers on the microspheres was 4.8. The results obtained in
      this work indicate that basic physicochemical characteristics of IgG can be
      acquired via electrophoretic mobility measurements using microgram quantities of
      the protein. 

PMID- 26296562
TI  - Clinical effectiveness and cost-effectiveness of tailored intensive liaison
      between primary and secondary care to identify individuals at risk of a first
      psychotic illness (the LEGs study): a cluster-randomised controlled trial.
AB  - BACKGROUND: General practitioners are usually the first health professionals to
      be contacted by people with early signs of psychosis. We aimed to assess whether
      increased liaison between primary and secondary care improves the clinical
      effectiveness and cost-effectiveness of detection of people with, or at high risk
      of developing, a first psychotic illness. METHODS: Our Liaison and Education in
      General Practices (LEGs) study was a cluster-randomised controlled trial of
      primary care practices (clusters) in Cambridgeshire and Peterborough, UK.
      Consenting practices were randomly allocated (1:1) to a 2 year low-intensity
      intervention (a postal campaign, consisting of biannual guidelines to help
      identify and refer individuals with early signs of psychosis) or a high-intensity
      intervention, which additionally included a specialist mental health professional
      who liaised with every practice and a theory-based educational package. Practices
      were not masked to group allocation. Practices that did not consent to be
      randomly assigned comprised a practice-as-usual (PAU) group. The primary outcome
      was number of referrals of patients at high risk of developing psychosis to the
      early intervention service per practice site. New referrals were assessed
      clinically and stratified into those who met criteria for high risk or first
      episode psychotic illness (FEP; together: psychosis true positives), and those
      who did not fulfil such criteria for psychosis (false positives). Referrals from
      PAU practices were also analysed. We assessed cost-effectiveness with decision
      analytic modelling in terms of the incremental cost per additional true positive
      identified. The trial is registered at the ISRCTN registry, number
      ISRCTN70185866. FINDINGS: Between Dec 22, 2009, and Sept 7, 2010, 54 of 104
      eligible practices provided consent and between Feb 16, 2010, and Feb 11, 2011,
      these practices were randomly allocated to interventions (28 to low intensity and
      26 to high intensity); the remaining 50 practices comprised the PAU group. Two
      high-intensity practices were excluded from the analysis. In the 2 year
      intervention period, high-intensity practices referred more FEP cases than did
      low-intensity practices (mean 1.25 [SD 1.2] for high intensity vs 0.7 [0.9] for
      low intensity; incidence rate ratio [IRR] 1.9, 95% CI 1.05-3.4, p=0.04), although
      the difference was not statistically significant for individuals at high risk of
      psychosis (0.9 [1.0] vs 0.5 [1.0]; 2.2, 0.9-5.1, p=0.08). For high risk and FEP
      combined, high-intensity practices referred both more true-positive (2.2 [1.7] vs
      1.1 [1.7]; 2.0, 1.1-3.6, p=0.02) and false-positive (2.3 [2.4] vs 0.9 [1.2]; 2.6,
      1.3-5.0, p=0.005) cases. Referral patterns did not differ between low-intensity
      and PAU practices. Total cost per true-positive referral in the 2 year follow-up
      was L26,785 in high-intensity practices, L27,840 in low-intensity practices, and
      L30,007 in PAU practices. INTERPRETATION: This intensive intervention to improve
      liaison between primary and secondary care for people with early signs of
      psychosis was clinically and cost effective. FUNDING: UK National Institute for
      Health Research.

PMID- 26296564
TI  - Prothrombotic state of patients with unexplained recurrent spontaneous abortion.
AB  - OBJECTIVE: To determine the effect of aspirin and low-molecular-weight heparin
      (LMWH) for women affected by recurrent spontaneous abortion (RSA). METHODS: The
      present prospective observational study included women with RSA (>= 2 previous
      spontaneous abortions) and those without a history of RSA attending Ren Ji
      Hospital, Shanghai, China, between March 2011 and March 2014. D-dimer levels,
      auto-antibodies, and platelet aggregation in response to arachidonic acid (AA)
      and adenosine diphosphate (ADP) were monitored before pregnancy. Women with
      unexplained RSA and increased platelet aggregation received low-dose aspirin, and
      those with elevated D-dimer levels (> 0.75 MUg/mL) received LMWH. Platelet
      aggregation in response to AA and ADP, and D-dimer levels were monitored during
      pregnancy. RESULTS: Among 517 participants with RSA, 325 had unexplained RSA.
      Compared with 63 control patients, those with unexplained RSA and two, three,
      four, or at least five previous spontaneous abortions had increased platelet
      aggregation in response to AA (P < 0.05 for all comparisons) but not to ADP.
      Among 37 women with unexplained RSA who became pregnant, aspirin reduced platelet
      aggregation in response to AA (P < 0.001). LMWH reduced D-dimer levels during
      pregnancy (P < 0.001). Among 37 women with unexplained RSA who became pregnant
      and completed the study, 33 (89.2%) had a live birth. CONCLUSION: Aspirin and
      LMWH maintained a lower thrombotic state and led to a high live birth rate among
      patients with unexplained RSA.

PMID- 26296566
TI  - Detection of the oomycete Pythium insidiosum by real-time PCR targeting the gene
      coding for exo-1,3-beta-glucanase.
AB  - Pythiosis is a life-threatening infectious disease caused by Pythium insidiosum.
      Early and accurate diagnosis is the key to prompt treatment and an improved
      prognosis for patients with pythiosis. An alternative to microbiological and
      immunological approaches for facilitating diagnosis of pythiosis is the PCR-based
      assay. Until recently, the ribosomal DNA (rDNA) region was the only target
      available for PCR-based detection of P. insidiosum. Failure to detect P.
      insidiosum by PCR amplification using the rDNA-specific primers has been
      reported. PinsEXO1, encoding an exo-1,3-beta-glucanase, is an alternative, novel
      and efficient target for identification of P. insidiosum by conventional PCR. In
      this study, we aimed to develop a real-time (RT)-PCR approach targeting PinsEXO1
      and compare its performance with conventional PCR for the detection of P.
      insidiosum. Both conventional and RT-PCR assays were positive for all 35 P.
      insidiosum strains tested, whilst all 58 control fungi were negative. The
      turnaround time for conventional PCR was 10 h, whilst that for RT-PCR was 7.5 h.
      The lowest amounts of genomic DNA template required for successful amplification
      by conventional and RT-PCR were 1 and 1 * 10(-4) ng, respectively. In conclusion,
      the RT-PCR assay retained 100% sensitivity and 100% specificity for detection of
      P. insidiosum. It showed a substantially improved analytical sensitivity and
      turnaround time that could improve diagnosis of pythiosis. The assay could also
      facilitate quantitative DNA analysis and epidemiological studies of P.
      insidiosum.

PMID- 26296567
TI  - Taxonomic description and genome sequence of Bacillus campisalis sp. nov., a
      member of the genus Bacillus isolated from a solar saltern.
AB  - The taxonomic position of a Gram-stain positive bacterium isolated from a solar
      saltern sample collected from Kanyakumari, coastal region of the Bay of Bengal,
      India, was analysed by using a polyphasic approach. The isolated strain,
      designated SA2-6T, had phenotypic characteristics that matched those of the genus
      Bacillus. The 16S rRNA gene sequence (1493 bases) of the novel strain was
      compared with those of previously studied Bacillus type strains and confirmed
      that the strain belongs to the genus Bacillus and was moderately closely related
      to the type strain of Bacillus foraminis at 97.5 % 16S rRNA gene sequence
      similarity, followed by those of Bacillus thioparans (96.9 %), Bacillus
      subterraneus (96.8 %), Bacillus jeotgali (96.6 %), Bacillus selenatarsenatis
      (96.6 %) and Bacillus boroniphilus (96.6 %). 16S rRNA gene sequence analysis
      indicated that strain SA2-6T differs from all other species of the genus Bacillus
      by at least 2.5 %. It contained MK-7 as the predominant menaquinone, meso
      diaminopimelic acid as the diagnostic cell-wall diamino acid, and iso-C15 : 0 and
      anteiso-C15 : 0 as major fatty acids. Major lipids were diphosphatidylglycerol
      (DPG), phosphatidylglycerol (PG) and phosphatidylethanolamine (PE). Based on data
      from this polyphasic study, strain SA2-6T is considered to represent a novel
      species of the genus Bacillus, for which the name Bacillus campisalis sp. nov. is
      proposed. The type strain is SA2-6T ( = MTCC 11848T = DSM 28801T). The draft
      genome of strain SA2-6T consisted of 5 183 363 bp with G+C content of 45.44 mol%,
      5352 predicted coding sequences, 191 RNAs and 479 subsystems.

PMID- 26296568
TI  - Bacillus paralicheniformis sp. nov., isolated from fermented soybean paste.
AB  - An isolate of a Gram-stain-positive, facultatively anaerobic, motile, rod-shaped,
      endospore-forming bacterium was recovered from soybean-based fermented paste.
      Phylogenetic analysis of the 16S rRNA gene indicated that the strain was most
      closely related to Bacillus sonorensis KCTC-13918T (99.5 % similarity) and
      Bacillus licheniformis DSM 13T (99.4 %). In phenotypic characterization, the
      novel strain was found to grow at 15-60  degrees C and to tolerate up to 10 %
      (w/v) NaCl. Furthermore, the strain grew in media with pH 6-11 (optimal growth at
      pH 7.0-8.0). The predominant cellular fatty acids were anteiso-C15 : 0 (37.7 %)
      and iso-C15 : 0 (31.5 %). The predominant isoprenoid quinone was menaquinone 7
      (MK-7). The cell-wall peptidoglycan contained meso-diaminopimelic acid. A draft
      genome sequence of the strain was completed and used for phylogenetic analysis.
      Phylogenomic analysis of all published genomes of species in the B. licheniformis
      group revealed that strains belonging to B. licheniformis clustered into two
      distinct groups, with group 1 consisting of B. licheniformis DSM 13T and 11 other
      strains and group 2 consisting of KJ-16T and four other strains. The DNA G+C
      content of strain KJ-16T was 45.9 % (determined from the genome sequence). Strain
      KJ-16T and another strain from group 2 were subsequently characterized using a
      polyphasic taxonomic approach and compared with strains from group 1 and another
      closely related species of the genus Bacillus. Based upon the consensus of
      phylogenetic and phenotypic analyses, we conclude that this strain represents a
      novel species within the genus Bacillus, for which the name Bacillus
      paralicheniformis sp. nov. is proposed, with type strain KJ-16T ( = KACC 18426T =
      NRRL B-65293T).

PMID- 26296565
TI  - Inflammation is increased with anxiety- and depression-like signs in a rat model
      of spinal cord injury.
AB  - Spinal cord injury (SCI) leads to increased anxiety and depression in as many as
      60% of patients. Yet, despite extensive clinical research focused on
      understanding the variables influencing psychological well-being following SCI,
      risk factors that decrease it remain unclear. We hypothesized that excitation of
      the immune system, inherent to SCI, may contribute to the decrease in
      psychological well-being. To test this hypothesis, we used a battery of
      established behavioral tests to assess depression and anxiety in spinally
      contused rats. The behavioral tests, and subsequent statistical analyses,
      revealed three cohorts of subjects that displayed behavioral characteristics of
      (1) depression, (2) depression and anxiety, or (3) no signs of decreased
      psychological well-being. Subsequent molecular analyses demonstrated that the
      psychological cohorts differed not only in behavioral symptoms, but also in
      peripheral (serum) and central (hippocampi and spinal cord) levels of pro
      inflammatory cytokines. Subjects exhibiting a purely depression-like profile
      showed higher levels of pro-inflammatory cytokines peripherally, whereas subjects
      exhibiting a depression- and anxiety-like profile showed higher levels of pro
      inflammatory cytokines centrally (hippocampi and spinal cord). These changes in
      inflammation were not associated with injury severity; suggesting that the
      association between inflammation and the expression of behaviors characteristic
      of decreased psychological well-being was not confounded by differential
      impairments in motor ability. These data support the hypothesis that inflammatory
      changes are associated with decreased psychological well-being following SCI. 

PMID- 26296569
TI  - Detection of Wzy/Wzz interaction in Shigella flexneri.
AB  - The O antigen (Oag) component of Shigella flexneri lipopolysaccharide (LPS) is
      important for virulence and a protective antigen. It is synthesized by the Wzy
      dependent mechanism. S. flexneri Wzy has 12 transmembrane segments and two large
      periplasmic loops. The modal chain length of the Oag is determined by Wzz.
      Experimental evidence supports multi-protein interactions in the Wzy-dependent
      pathway. However, evidence for direct interaction of Wzy with the other proteins
      of the Wzy-dependent pathway is limited. Initially, we purified Wzy-GFP-His8 and
      detected the presence of a dimeric form. In vivo cross-linking was then performed
      in an S. flexneri wzy mutant strain carrying plasmids encoding Wzy-GFP-His8 and
      untagged Wzz. Following solubilization with n-dodecyl-beta-D-maltopyranoside
      (DDM) and affinity purification of Wzy-GFP-His8, Western immunoblotting with Wzz
      antibody detected co-purification of Wzz; this was supported by MS analysis. To
      the best of our knowledge, this is the first reported isolation of a complex
      between Wzy and Wzz. Wzy mutants (WzyR164A, WzyV92M, WzyY137H, and WzyR250K)
      whose properties are affected by Wzz were able to form complexes with Wzz. Their
      mutational alterations did not affect the interaction of Wzy with Wzz. Thus, the
      interaction may involve many regions of Wzy.

PMID- 26296570
TI  - RNA interference of influenza A virus replication by microRNA-adapted lentiviral
      loop short hairpin RNA.
AB  - Limitations of the current vaccines and antivirals against influenza A virus
      (IAV) pandemic underscore the urgent need for developing novel anti-influenza
      strategies. RNA interference (RNAi) induced by small interfering RNA (siRNA) has
      become a powerful new means to inhibit viral infection in a gene-specific manner.
      However, the efficacy of the siRNA delivery platform and the relatively high cost
      of administration have hindered widespread application of siRNA. In this study,
      we developed a microRNA (miRNA)-30-based lentivirus delivery system by embedding
      a synthetic short hairpin RNA (shRNA) stem into the context of endogenous
      precursor of miRNA-30 (shRNAmir) to express a silencer of the influenza gene. We
      showed that the miRNA-based lentivirus vector was able to express and process a
      single nucleoprotein (NP)-targeting shRNAmir, which could potently inhibit IAV
      replication. We further showed that miRNA-based lentivirus vector carrying
      tandemly linked NP and polymerase PB1 shRNAmirs could express and process double
      shRNAmirs. Despite the relatively low levels of NP and PB1 miRNAs produced in the
      stably transduced cells, the combination of two miRNAs exerted a great degree of
      inhibition on influenza infection. Given the advantage of combinatorial RNAi in
      preventing emergence of mutant virus, miRNA-based lentiviral vectors are valuable
      tools for anitiviral activities. To the best of our knowledge, this is the first
      study demonstrating that a miRNA-based RNAi strategy can be applied for better
      control of influenza virus infection. 

PMID- 26296571
TI  - Hepatitis C virus Genotype 1a core gene nucleotide patterns associated with
      hepatocellular carcinoma risk.
AB  - Specific sequence changes in codons 70 and 91 of the hepatitis C virus genotype
      1b (HCV GT1b) core gene have been associated with increased risk of
      hepatocellular carcinoma (HCC). Essentially all previous studies were conducted
      in Asian populations with a wide range of liver disease, and none were conducted
      specifically in GT1a-infected individuals. We conducted a pilot study in a
      multiethnic population in the USA with HCV-related cirrhosis to determine if this
      association extended to GT1a-infected individuals and to determine if other
      sequence changes in the HCV core gene were associated with HCC risk. HCV core
      gene sequences from sera of 90 GT1 HCV carriers with cirrhosis (42 with HCC) were
      analysed using standard RT-PCR-based procedures. Nucleotide sequence data were
      compared with reference sequences available from GenBank. The frequency of
      sequence changes in codon 91 was not statistically different between HCC (7/19)
      and non-HCC (11/22) GT1b carriers. In GT1a carriers, sequence changes in codon 91
      were observed less often than in GT1b carriers but were not observed in non-HCC
      subjects (4/23 vs 0/26, P = 0.03, Fisher's exact test). Sequence changes in codon
      70 were not distributed differently between HCC and non-HCC GT1a and 1b carriers.
      Most importantly, for GT1a carriers, a panel of specific nucleotide changes in
      other codons was collectively present in all subjects with HCC, but not in any of
      the non-HCC patients. The utility of this test panel for early detection of HCC
      in GT1a-infected individuals needs to be assessed in larger populations,
      including longitudinal studies. 

PMID- 26296572
TI  - MicroRNA hsa-miR-29a-3p modulates CYP2C19 in human liver cells.
AB  - Cytochrome P450 2C19 (CYP2C19) is involved in the metabolism of many drugs.
      Extensive studies have demonstrated that genetic variants and endogenous and
      environmental factors play important roles in the expression of CYP2C19. However,
      the role of microRNAs (miRNAs) in controlling CYP2C19 expression has not been
      investigated completely. In the present study, we performed in silico analysis to
      rank putative miRNA/CYP2C19 hybrids with regards to the predicted stabilities of
      their duplexes and then we applied a series of biochemical and molecular assays
      to elucidate the underlying functional mechanisms for the regulation of CYP2C19
      by miRNAs. In silico analysis indicated that hsa-miR-23a-3p and hsa-miR-29a-3p
      target the coding region of CYP2C19 with hybrid stabilities of -27.5kcal/mol and 
      23.3kcal/mol, respectively. RNA electrophoresis mobility shift assays showed that
      both hsa-miR-23a-3p and hsa-miR-29a-3p miRNAs were able to bind directly to their
      cognate targets in the CYP2C19 transcript. Further, a significant inverse
      correlation was found between chemically-induced up-regulation of hsa-miR-29a-3p
      and CYP2C19 expression in HepaRG cells. In addition, inverse correlations were
      also observed in human liver tissue samples between the level of CYP2C19 mRNA
      expression and both hsa-miR-23a-3p and hsa-miR-29a-3p levels. All these results
      demonstrated the suppressing role of hsa-miR-29a-3p on CYP2C19 expression. 

PMID- 26296574
TI  - Streptomyces sasae sp. nov., isolated from bamboo (Sasa borealis) rhizosphere
      soil.
AB  - A novel strain of Gram-staining-positive actinobacterium, designated strain JR
      39T, was isolated from the rhizosphere soil of bamboo (Sasa borealis) sampled in
      Damyang, Korea, and its taxonomic position was investigated by a polyphasic
      approach. The isolate formed flexuous chains of spores that were cylindrical and
      smooth-surfaced. Strain JR-39T grew at 4-37  degrees C (optimum 28  degrees C).
      The pH range for growth was pH 5-10 (optimum pH 6-8) and the NaCl range for
      growth was 0-5 % (w/v) with optimum growth at 1 % NaCl. The cell-wall
      peptidoglycan contained ll-diaminopimelic acid, glutamic acid, alanine and
      glycine. Whole-cell hydrolysates mainly contained glucose, mannose, ribose and
      rhamnose. Predominant menaquinones were MK-9 (H6), MK-9 (H8) and MK-9 (H4). The
      major cellular fatty acids were anteiso-C15 : 0, iso-C16 : 0, iso-C15 : 0 and iso
      C14 : 0. The G+C content of the DNA was 72.3 +/- 0.34 mol%. Phylogenetic analyses
      based on 16S rRNA gene sequence analysis indicated that strain JR-39T belonged to
      the genus Streptomyces, showing the highest sequence similarity to Streptomyces
      panaciradicis 1MR-8T (99.4 %), Streptomyces capoamus JCM 4734T (98.8 %),
      Streptomyces galbus DSM 40089T (98.7 %), Streptomyces longwoodensis LMG 20096T
      (98.7 %), Streptomyces bungoensis NBRC 15711T (98.7 %) and Streptomyces
      rhizophilus JR-41T (98.7 %). However, DNA-DNA hybridization assays, as well as
      physiological and biochemical analyses, showed that strain JR-39T could be
      differentiated from its closest phylogenetic relatives. On the basis of the
      phenotypic and genotypic characteristics, strain JR-39T represents a novel
      species for which the name Streptomyces sasae sp. nov. is proposed. The type
      strain is JR-39T ( = KACC 17182T = NBRC 109809T).

PMID- 26296573
TI  - Caffeine promotes anti-tumor immune response during tumor initiation: Involvement
      of the adenosine A2A receptor.
AB  - Epidemiologic studies depict a negative correlation between caffeine consumption
      and incidence of tumors in humans. The main pharmacological effects of caffeine
      are mediated by antagonism of the adenosine receptor, A2AR. Here, we examine
      whether the targeting of A2AR by caffeine plays a role in anti-tumor immunity. In
      particular, the effects of caffeine are studied in wild-type and A2AR knockout
      (A2AR(-/-)) mice. Tumor induction was achieved using the carcinogen 3
      methylcholanthrene (3-MCA). Alternatively, tumor cells, comprised of 3-MCA
      induced transformed cells or B16 melanoma cells, were inoculated into animal
      footpads. Cytokine release was determined in a mixed lymphocyte tumor reaction
      (MLTR). According to our findings, caffeine-consuming mice (0.1% in water)
      developed tumors at a lower rate compared to water-consuming mice (14% vs. 53%,
      respectively, p=0.0286, n=15/group). Within the caffeine-consuming mice, tumor
      free mice displayed signs of autoimmune alopecia and pronounced leukocyte
      recruitment intocarcinogen injection sites. Similarly, A2AR(-/-) mice exhibited
      reduced rates of 3-MCA-induced tumors. In tumor inoculation studies, caffeine
      treatment resulted in inhibition of tumor growth and elevation in proinflammatory
      cytokine release over water-consuming mice, as depicted by MLTR. Addition of the
      adenosine receptor agonist, NECA, to MLTR resulted in a sharp decrease in
      IFNgamma levels; this was reversed by the highly selective A2AR antagonist,
      ZM241385. Thus, immune response modulation through either caffeine or genetic
      deletion of A2AR leads to a Th1 immune profile and suppression of carcinogen
      induced tumorigenesis. Taken together, our data suggest that the use of
      pharmacologic A2AR antagonists may hold therapeutic potential in diminishing the
      rate of cancer development. 

PMID- 26296575
TI  - Distraction, restrained eating and disinhibition: An experimental study of food
      intake and the impact of 'eating on the go'.
AB  - To assess the impact of distraction on subsequent eating, 60 females consumed a
      cereal bar while watching TV, walking or talking, and their subsequent desire to
      eat and food intake were assessed. No effects were found for desire to eat. But
      while those higher in restrained eating consumed less overall and fewer calories
      after watching TV or talking, they consumed more overall and more calories
      (specifically five times more chocolate) if the cereal bar was eaten while
      walking. 'Eating on the go' may disinhibit restrained eaters either as a form of
      distraction or by offering a justification to overeat.

PMID- 26296576
TI  - A novel astrovirus from dromedaries in the Middle East.
AB  - The recent emergence of Middle East respiratory syndrome coronavirus from the
      Middle East and its discovery from dromedary camels has boosted interest in the
      search for novel viruses in dromedaries. The existence of astroviruses (AstVs) in
      dromedaries was previously unknown. We describe the discovery of a novel
      dromedary camel AstV (DcAstV) from dromedaries in Dubai. Among 215 dromedaries,
      DcAstV was detected in faecal samples of four [three (1.5 %) adult dromedaries
      and one (8.3 %) dromedary calf] by reverse transcription-PCR. Sequencing of the
      four DcAstV genomes and phylogenetic analysis showed that the DcAstVs formed a
      distinct cluster. Although DcAstV was most closely related to a recently
      characterized porcine AstV 2, their capsid proteins only shared 60-66 % amino
      acid identity, with a mean amino acid genetic distance of 0.372. Notably, the N
      terminal halves of the capsid proteins of DcAstV shared <= 85 % amino acid
      identity, but the C-terminal halves only shared <= 49 % amino acid identity
      compared with the corresponding proteins in other AstVs. A high variation of the
      genome sequences of DcAstV was also observed, with a mean amino acid genetic
      distance of 0.214 for ORF2 of the four strains. Recombination analysis revealed a
      possible recombination event in ORF2 of strain DcAstV-274. The low Ka/Ks ratios
      (number of non-synonymous substitutions per non-synonymous site to number of
      synonymous substitutions per synonymous site) of the four ORFs in the DcAstV
      genomes supported the suggestion that dromedaries are the natural reservoir where
      AstV is stably evolving. These results suggest that AstV is a novel species of
      the genus Mamastrovirus in the family Astroviridae. Further studies are important
      to understand the pathogenic potential of DcAstV. 

PMID- 26296577
TI  - Lysinibacter cavernae gen. nov., sp. nov., a new  member of the family
      Microbacteriaceae isolated  from a karst cave.
AB  - A Gram-stain-positive, aerobic, straight or slightly bent rod-shaped, non-motile,
      non-spore-forming bacterium, designated strain CC5-806T, was isolated from a soil
      sample collected from a wild karst cave in the Wulong region, Chongqing, PR China
      and examined using a polyphasic approach to clarify its taxonomic position. This
      bacterium did not produce substrate mycelium or aerial hyphae, and no diffusible
      pigments were observed on the media tested. Strain CC5-806T grew optimally
      without NaCl at 20  degrees C and at pH 7.0. Phylogenetic analysis, based on 16S
      rRNA gene sequences, indicated that strain CC5-806T belonged to the family
      Microbacteriaceae and showed the highest levels of 16S rRNA gene sequence
      similarities with Frigoribacterium endophyticum EGI 6500707T (97.56 %),
      Frigoribacterium faeni 801T (97.53 %) and Glaciihabitans tibetensis MP203T (97.42
      %). Phylogenetic trees revealed that strain CC5-806T did not show a clear
      affiliation to any genus within the family Microbacteriaceae. The DNA G+C content
      of strain CC5-806T was 62.6 mol%. The cell-wall peptidoglycan contained l-lysine
      as a diagnostic diamino acid. The predominant menaquinones were MK-11, MK-10 and
      MK-9. Phosphatidylglycerol, diphosphatidylglycerol, an unidentified glycolipid,
      four unidentified phospholipids and other polar lipids were detected in the polar
      lipid extracts. The major fatty acids were anteiso-C15 : 0, iso-C16 : 0 and iso
      C14 : 0. On the basis of the phylogenetic analysis, and phenotypic and
      chemotaxonomic characteristics, strain CC5-806T was distinguishable from
      phylogenetically related genera in the family Microbacteriaceae. It represents a
      novel species of a novel genus, for which the name Lysinibacter cavernae gen.
      nov., sp. nov. is proposed. The type strain is CC5-806T ( = DSM 27960T = CGMCC
      1.14983T).

PMID- 26296579
TI  - [Vascular medicine of the future].

PMID- 26296578
TI  - Resveratrol inhibits rhinovirus replication and expression of inflammatory
      mediators in nasal epithelia.
AB  - Human rhinoviruses (HRV), the cause of common colds, are the most frequent
      precipitants of acute exacerbation of asthma and chronic obstructive pulmonary
      disease, as well as causes of other serious respiratory diseases. No vaccine or
      antiviral agents are available for the prevention or treatment of HRV infection.
      Resveratrol exerts antiviral effect against different DNA and RNA viruses. The
      antiviral effect of a new resveratrol formulation containing carboxymethylated
      glucan was analyzed in H1HeLa cell monolayers and ex vivo nasal epithelia
      infected with HRV-16. Virus yield was evaluated by plaque assay and expression of
      viral capsid proteins by Western blot. IL-10, IFN-beta, IL-6, IL-8 and RANTES
      levels were evaluated by ELISA assay. ICAM-1 was assessed by Western blot and
      immunofluorescence. Resveratrol exerted a high, dose-dependent, antiviral
      activity against HRV-16 replication and reduced virus-induced secretion of IL-6,
      IL-8 and RANTES to levels similar to that of uninfected nasal epithelia. Basal
      levels of IL-6 and RANTES were also significantly reduced in uninfected epithelia
      confirming an anti-inflammatory effect of the compound. HRV-induced expression of
      ICAM-1 was reversed by resveratrol. Resveratrol may be useful for a therapeutic
      approach to reduce HRV replication and virus-induced cytokine/chemokine
      production. 

PMID- 26296580
TI  - Paenibacillus physcomitrellae sp. nov., isolated from the moss Physcomitrella
      patens.
AB  - A Gram-stain-positive, facultatively anaerobic and rod-shaped bacterium,
      designated strain XBT, was isolated from Physcomitrella patens growing in
      Beijing, China. The isolate was identified as a member of the genus Paenibacillus
      based on phenotypic characteristics and phylogenetic inferences. The novel strain
      was spore-forming, motile, catalase-negative and weakly oxidase-positive. Optimal
      growth of strain XBT occurred at 28 degrees C and pH 7.0-7.5. The major polar
      lipids contained diphosphatidylglycerol, phosphatidylglycerol,
      phosphatidylethanolamine and several unidentified components, including one
      phospholipid, two aminophospholipids, three glycolipids, one aminolipid and one
      lipid. The predominant isoprenoid quinone was MK-7. The diamino acid found in the
      cell-wall peptidoglycan was meso-diaminopimelic acid. The major fatty acid
      components (>5 %) were anteiso-C15 : 0 (51.2 %), anteiso-C17 : 0 (20.6 %), iso
      C16 : 0 (8.3 %) and C16 : 0 (6.7 %). The G+C content of the genomic DNA was 53.3
      mol%. Phylogenetic analysis, based on the 16S rRNA gene sequence, showed that
      strain XBT fell within the evolutionary distances encompassed by the genus
      Paenibacillus; its closest phylogenetic neighbour was Paenibacillus yonginensis
      DCY84T (96.6 %). Based on phenotypic, chemotaxonomic and phylogenetic properties,
      strain XBT is considered to represent a novel species of the genus Paenibacillus,
      for which the name Paenibacillus physcomitrellae sp. nov., is proposed. The type
      strain is XBT ( = CGMCC 1.15044T = DSM 29851T). 

PMID- 26296581
TI  - Rapid assay of A2058T-mutated 23S rRNA allelic profiles associated with high
      level macrolide resistance in Moraxella catarrhalis.
AB  - We report on a restriction fragment-length polymorphism (HpyCH4III) assay for
      profile analysis of 23S rRNA gene A2058T-mutated alleles associated with high
      level macrolide resistance in Moraxella catarrhalis. Our assay results were
      supported by DNA sequencing analysis, allowed for simultaneous testing of many
      strains, and produced results from pure-cultured colonies within 4 h.

PMID- 26296582
TI  - Using glomerular filtration rate estimating equations: clinical and laboratory
      considerations.

PMID- 26296584
TI  - It isn't like this on TV: Revisiting CPR survival rates depicted on popular TV
      shows.
AB  - BACKGROUND: Public perceptions of cardiopulmonary resuscitation (CPR) can be
      influenced by the media. Nearly two decades ago, a study found that the rates of
      survival following CPR were far higher in popular TV shows than actual rates. In
      recent years, major strides toward enhanced education and communication around
      life sustaining interventions have been made. This study aimed to reassess the
      accuracy of CPR portrayed by popular medical TV shows. Additionally, we sought to
      determine whether these shows depicted discussions of care preferences and
      referenced advance directives. METHODS: Three trained research assistants
      independently coded two leading medical dramas airing between 2010 and 2011,
      Grey's Anatomy and House. Patient characteristics, CPR survival rates, and goals
      of care discussions were recorded. RESULTS: CPR was depicted 46 times in the 91
      episodes, with a survival rate of 69.6%. Among those immediately surviving
      following CPR, the majority (71.9%) survived to hospital discharge and 15.6% died
      before discharge. Advance directive discussions only occurred for two patients,
      and preferences regarding code status (8.7%), intubation (6.5%) and feeding
      (4.3%) rarely occurred. CONCLUSIONS: Both popular TV shows portrayed CPR as more
      effective than actual rates. Overall, the shows portrayed an immediate survival
      rate nearly twice that of actual survival rates. Inaccurate TV portrayal of CPR
      survival rates may misinform viewers and influence care decisions made during
      serious illness and at end of life.

PMID- 26296583
TI  - Long-term evolution after in-hospital cardiac arrest in children: Prospective
      multicenter multinational study.
AB  - OBJECTIVE: The main objective was to study survival and neurologic evolution of
      children who suffered in-hospital pediatric cardiac arrest (CA). The secondary
      objective was to analyze the influence of risk factors on the long term outcome
      after CA. METHODS: prospective, international, observational, multicentric study
      in 48 hospitals of 12 countries. CA in children between 1 month and 18 years were
      analyzed using the Utstein template. Survival and neurological state measured by
      Pediatric Cerebral Performance Category (PCPC) scale one year after hospital
      discharge was evaluated. RESULTS: 502 patients with in-hospital CA were
      evaluated. 197 of them (39.2%) survived to hospital discharge. PCPC at hospital
      discharge was available in 156 of survivors (79.2%). 76.9% had good neurologic
      state (PCPC 1-2) and 23.1% poor PCPC values (3-6). One year after cardiac arrest
      we could obtain data from 144 patients (28.6%). PCPC was available in 116
      patients. 88 (75.9%) had a good neurologic evaluation and 28 (24.1%) a poor one.
      A neurological deterioration evaluated by PCPC scale was observed in 40 patients
      (7.9%). One year after cardiac arrest PCPC scores compared to hospital discharge
      had worsen in 7 patients (6%), remained constant in 103 patients (88.8%) and had
      improved in 6 patients (5.2%). CONCLUSION: Survival one year after cardiac arrest
      in children after in-hospital cardiac arrest is high. Neurologic outcome of these
      children a year after cardiac arrest is mostly the same as after hospital
      discharge. The factors associated with a worst long-term neurological outcome are
      the etiology of arrest being a traumatic or neurologic illness, and the
      persistency of higher lactic acid values 24h after ROSC. A standardised basic
      protocol even practicable for lower developed countries would be a first step for
      the new multicenter studies.

PMID- 26296585
TI  - Chest compressions in newborn animal models: A review.
AB  - OBJECTIVE: Much of the knowledge about the optimal way to perform chest
      compressions (CC) in newborn infants is derived from animal studies. The
      objective of this review was to identify studies of CC in newborn term animal
      models and review the evidence. We also provide an overview of the different
      models. METHODS:  DATA SOURCES: MEDLINE, EMBASE and CINAHL, until September 29th
      2014. Study eligibility criteria and interventions: term newborn animal models
      where CC was performed. RESULTS: Based on 419 retrieved studies from MEDLINE and
      502 from EMBASE, 28 studies were included. No additional studies were identified
      in CINAHL. Most of the studies were performed in pigs after perinatal transition
      without long-term follow-up. The models differed widely in methodological
      aspects, which limits the possibility to compare and synthesize findings. Studies
      uncommonly reported the method for randomization and allocation concealment, and
      a limited number were blinded. Only the evidence in favour of the two-thumb
      encircling hands technique for performing CC, a CC to ventilation ratio of 3:1;
      and that air can be used for ventilation during CC; was supported by more than
      one study. CONCLUSIONS: Animal studies should be performed and reported with the
      same rigor as in human randomized trials. Good transitional and survival models
      are needed to further increase the strength of the evidence derived from animal
      studies of newborn chest compressions.

PMID- 26296586
TI  - David Oliver: What you don't learn at medical school.

PMID- 26296587
TI  - Niastella gongjuensis sp. nov., isolated from greenhouse soil.
AB  - An aerobic, Gram-stain-negative, non-flagellated, long rod or rod-shaped
      bacterial strain, 5GH22-11(T), was isolated from a soil sample of a greenhouse in
      Gongju, Republic of Korea. According to 16S rRNA gene sequence analysis, strain
      5GH22-11(T) showed the highest sequence similarities with Niastella populi THYL
      44(T) (97.1%), Niastella koreensis GR20-10T (95.7%) and Niastella yeongjuensis
      GR20-13(T) (95.6%), and < 3% sequence similarity with all other species with
      validly published names. The phylogenetic tree also showed strain 5GH22-11(T)
      formed a compact cluster with members of the genus Niastella. DNA-DNA
      hybridization revealed strain 5GH22-11(T) is a novel species, showing far less
      than 70% DNA-DNA relatedness with Niastella populi THYL-44(T). Strain 5GH22-11(T)
      contained iso-C15 : 0 (34.3%), iso-C17 : 0 3-OH (24.8%) and iso-C15 : 1 G (18.2%)
      as the major fatty acids; phosphatidylethanolamine, six unknown aminolipids, two
      unknown lipids and one unknown phospholipid as the polar lipids; and MK-7 as the
      predominant isoprenoid quinone. The DNA G+C content was 41.4 mol%. Based on these
      phylogenetic, physiological and chemotaxonomic data, it was demonstrated that
      strain 5GH22-11(T) represents a novel species of the genus Niastella, for which
      the name Niastella gongjuensis sp. nov. is proposed. The type strain is 5GH22
      11(T) ( = KACC 17339(T) [corrected] = JCM 19941(T)).

PMID- 26296588
TI  - Molecular identification and bioinformatics analysis of a potential anti-vector
      vaccine candidate, 15-kDa salivary gland protein (Salp15), from Ixodes affinis
      ticks.
AB  - Salp15, a 15-kDa salivary gland protein plays an important role in tick blood
      feeding and transmission of Borrelia burgdorferi, the causative agent of Lyme
      borreliosis. The comparative studies reveal that Salp15 is a genetically
      conserved protein across various Ixodes species. In this study, we have
      identified a Salp15 homolog, designated as Iaff15, from Ixodes affinis ticks that
      are the principal enzootic vectors of B. burgdorferi sensu stricto in the
      southeastern part of the United States. Comparison of the annotated amino acid
      sequences showed that Iaff15 share 81% homology with I. sinensis Salp15 homolog
      and 64% homology with I. scapularis Salp15. Phylogenetic analysis revealed that
      Iaff15 come within the same clade with I. sinensis, I. scapularis, and I.
      pacificus Salp15 homologs. The bioinformatics analysis of the posttranslational
      modifications prediction revealed that all the Salp15 family members contain
      glycosylation sites. In addition, Iaff15 carried a higher number of Casein Kinase
      II phosphorylation sites in comparison to the other Salp15 family members.
      Collectively, high sequence conservation distributed over the entire amino acids
      sequence not only suggests an important role for Iaff15 in I. affinis blood
      feeding and vector-pathogen interactions but may also lead to the development of
      an anti-vector vaccine against this group of ticks. 

PMID- 26296589
TI  - Pre-differentiation of mesenchymal stromal cells in combination with a
      microstructured nerve guide supports peripheral nerve regeneration in the rat
      sciatic nerve model.
AB  - Many bioartificial nerve guides have been investigated pre-clinically for their
      nerve regeneration-supporting function, often in comparison to autologous nerve
      transplantation, which is still regarded as the current clinical gold standard.
      Enrichment of these scaffolds with cells intended to support axonal regeneration
      has been explored as a strategy to boost axonal regeneration across these nerve
      guides Ansselin et al. (1998). In the present study, 20 mm rat sciatic nerve
      defects were implanted with a cell-seeded microstructured collagen nerve guide
      (Perimaix) or an autologous nerve graft. Under the influence of seeded, pre
      differentiated mesenchymal stromal cells, axons regenerated well into the
      Perimaix nerve guide. Myelination-related parameters, like myelin sheath
      thickness, benefitted from an additional seeding with pre-differentiated
      mesenchymal stromal cells. Furthermore, both the number of retrogradely labelled
      sensory neurons and the axon density within the implant were elevated in the cell
      seeded scaffold group with pre-differentiated mesenchymal stromal cells. However,
      a pre-differentiation had no influence on functional recovery. An additional cell
      seeding of the Perimaix nerve guide with mesenchymal stromal cells led to an
      extent of functional recovery, independent of the differentiation status, similar
      to autologous nerve transplantation. These findings encourage further
      investigations on pre-differentiated mesenchymal stromal cells as a cellular
      support for peripheral nerve regeneration.

PMID- 26296590
TI  - Recent advances in Echinococcus genomics and stem cell research.
AB  - Alveolar and cystic echinococcosis, caused by the metacestode larval stages of
      the tapeworms Echinococcus multilocularis and Echinococcus granulosus,
      respectively, are life-threatening diseases and very difficult to treat. The
      introduction of benzimidazole-based chemotherapy, which targets parasite beta
      tubulin, has significantly improved the life-span and prognosis of echinococcosis
      patients. However, benzimidazoles show only parasitostatic activity, are
      associated with serious adverse side effects and have to be administered for very
      long time periods, underlining the need for new drugs. Very recently, the nuclear
      genomes of E. multilocularis and E. granulosus have been characterised, revealing
      a plethora of data for gaining a deeper understanding of host-parasite
      interaction, parasite development and parasite evolution. Combined with extensive
      transcriptome analyses of Echinococcus life cycle stages these investigations
      also yielded novel clues for targeted drug design. Recent years also witnessed
      significant advancements in the molecular and cellular characterisation of the
      Echinococcus 'germinative cell' population, which forms a unique stem cell system
      that differs from stem cells of other organisms in the expression of several
      genes associated with the maintenance of pluripotency. As the only parasite cell
      type capable of undergoing mitosis, the germinative cells are central to all
      developmental transitions of Echinococcus within the host and to parasite
      expansion via asexual proliferation. In the present article, we will briefly
      introduce and discuss recent advances in Echinococcus genomics and stem cell
      research in the context of drug design and development. Interestingly, it turns
      out that benzimidazoles seem to have very limited effects on Echinococcus
      germinative cells, which could explain the high recurrence rates observed after
      chemotherapeutic treatment of echinococcosis patients. This clearly indicates
      that future efforts into the development of parasitocidal drugs should also
      target the parasite's stem cell system. 

PMID- 26296591
TI  - A preliminary investigation into the genetic variation and population structure
      of Taenia hydatigena from Sardinia, Italy.
AB  - Cysticercosis caused by the metacestode stage of Taenia hydatigena is endemic in
      Sardinia. Information on the genetic variation of this parasite is important for
      epidemiological studies and implementation of control programs. Using two
      mitochondrial genes, the cytochrome c oxidase subunit 1 (cox1) and the NADH
      dehydrogenase subunit 1 (ND1) we investigated the genetic variation and
      population structure of Cysticercus tenuicollis from Sardinian intermediate hosts
      and compared it to that from other hosts from various geographical regions. The
      parsimony cox1 network analysis indicated the existence of a common lineage for
      T. hydatigena and the overall diversity and neutrality indices indicated
      demographic expansion. Using the cox1 sequences, low pairwise fixation index
      (Fst) values were recorded for Sardinian, Iranian and Palestinian sheep C.
      tenuicollis which suggested the absence of genetic differentiation. Using the ND1
      sequences, C. tenuicollis from Sardinian sheep appeared to be differentiated from
      those of goat and pig origin. In addition, goat C. tenuicollis were genetically
      different from adult T. hydatigena as indicated by the statistically significant
      Fst value. Our results are consistent with biochemical and morphological studies
      that suggest the existence of variants of T. hydatigena. 

PMID- 26296592
TI  - Neuroanatomical and neurochemical basis of parenting: Dynamic coordination of
      motivational, affective and cognitive processes.
AB  - This article is part of a Special Issue "Parental Care". Becoming a parent is
      arguably the most profound transforming experience in life. It is also inherently
      very emotionally and physically demanding, such that the reciprocal interaction
      with the young changes the brain and behavior of the parents. In this review, we
      examine the neurobiological mechanisms of parenting primarily discussing recent
      research findings in rodents and primates, especially humans. We argue that it is
      essential to consider parenting within a conceptual framework that recognizes the
      dynamics of the reciprocal mother-young relationship, including both the
      complexity and neuroplasticity of its underlying mechanisms. Converging research
      suggests that the concerted activity of a distributed network of subcortical and
      cortical brain structures regulates different key aspects of parenting, including
      the sensory analysis of infant stimuli as well as motivational, affective and
      cognitive processes. The interplay among these processes depends on the action of
      various neurotransmitters and hormones that modulate the timely and coordinated
      execution of caregiving responses of the maternal circuitry exquisitely attuned
      to the young's affect, needs and developmental stage. We conclude with a summary
      and a set of questions that may guide future research. 

PMID- 26296593
TI  - Trauma in the elderly: Burden or opportunity?

PMID- 26296594
TI  - How aggressively should neurosurgeons treat elderly patients with severe blunt
      traumatic brain injury?

PMID- 26296596
TI  - Osteonecrosis of the Jaw in Association With Chemotherapy in the Setting of
      Cutaneous T-Cell Lymphoma.
AB  - T-cell lymphomas (TCLs) account for approximately 15 to 20% of all non-Hodgkin
      lymphomas in the United States. The most common form of TCL is cutaneous TCL
      (CTCL), with Sezary syndrome and mycosis fungoides being the most prevalent
      subtypes. Sezary syndrome is the more aggressive form and often is referred to as
      a late-stage variant of mycosis fungoides. Clinically, it is characterized by
      diffuse erythroderma, cutaneous edema, pruritus, nonhealing cutaneous ulcers, and
      lymphadenopathy. Patients also can present with changes to their nails,
      hyperpigmentation, alopecia, palmoplantar keratoderma, ectropion, and
      hepatosplenomegaly. The overall prognosis for patients with Sezary syndrome is
      poor. The literature regarding oral manifestations of CTCL mostly report those of
      mycosis fungoides because it is the most common subtype of CTCL. Currently, there
      are only 2 reports in the scientific literature of intraoral manifestations of
      Sezary syndrome. This case report describes a patient with Sezary syndrome who
      presented with rapidly progressing erythematous lesions of the gingiva and
      multifocal osteonecrosis of the maxilla and mandible. This is the third reported
      case of an intraoral manifestation of Sezary syndrome and the first reported case
      of osteonecrosis in the setting of CTCL. 

PMID- 26296595
TI  - Comparative Effectiveness on Cognitive Asthma Outcomes of the SHARP Academic
      Asthma Health Education and Counseling Program and a Non-Academic Program.
AB  - Asthma morbidity and mortality is higher among older school-age children and
      early adolescents than other age groups across the lifespan. NIH recommended
      expanding asthma education to schools and community settings to meet cognitive
      outcomes that have an impact on morbidity and mortality. Guided by the acceptance
      of asthma model, an evidence-guided, comprehensive school-based academic health
      education and counseling program, Staying Healthy-Asthma Responsible & PreparedTM
      (SHARP), was developed. The program complements existing school curricula by
      integrating biology, psychology, and sociology content with related spelling,
      math, and reading and writing assignments. Feasibility, benefits, and efficacy
      have been established. We compared the effectiveness of SHARP to a non-academic
      program, Open Airways for Schools, in improving asthma knowledge and reasoning
      about symptom management. A two-group, cluster-randomized, single-blinded design
      was used with a sample of 205 students in grades 4-5 with asthma and their
      caregivers. Schools were matched prior to randomization. The unit of analysis was
      the student. Certified elementary school teachers delivered the programs during
      instructional time. Data were collected from student/caregiver dyads at baseline
      and at 1, 12, and 24 months after the intervention. In multilevel modeling,
      students enrolled in the academic SHARP program demonstrated significant (p<
      .001) improvement in asthma knowledge and reasoning over students enrolled in the
      non-academic program. Knowledge advantages were retained at 24 months. Findings
      support delivery in schools of the SHARP academic health education program for
      students with asthma.

PMID- 26296597
TI  - Maxillofacial Fractures in Women and Men: A 10-Year Retrospective Study.
AB  - PURPOSE: The purpose of this study was to evaluate and compare the demographic
      characteristics of maxillofacial fractures between women and men in China.
      PATIENTS AND METHODS: The sample was composed of all patients who sustained
      maxillofacial fractures during a 10-year period (2000 through 2009). Incidences,
      age distributions, etiologies, fracture patterns, associated injuries, and
      occupation distributions were recorded and analyzed. Data analysis included the
      chi(2) test, the Fisher exact test, and the t test. A P value less than .05 was
      considered significant. RESULTS: There were 1,131 patients (881 male and 250
      female) who sustained maxillofacial fractures, with a male-to-female ratio of
      3.5:1. Male patients sustained injuries most frequently during the autumn (P =
      .048), whereas female patients sustained more maxillofacial injuries during the
      summer (P = .006). Men sustained motorcycle (P = .023) and assault-related
      accidents (P = .036) more frequently than women, whereas women were more
      frequently injured in bicycle-related accidents (P < .001) or falling while at
      ground level (P = .001) than men. Women presented more frequently with condylar
      fracture than men (P = .028), whereas men were more prone to symphysis fractures
      than women (P = .037). For drivers, only men were involved (P = .001). Male
      workers sustained maxillofacial fractures more frequently than female workers (P
      < .001). Female children, students, and company staff were more prone to
      maxillofacial fractures than their male counterparts (P = .010, P = .004, and P =
      .044 respectively). CONCLUSIONS: The demographic characteristics of maxillofacial
      fractures in female patients considerably differ from those in male patients.

PMID- 26296598
TI  - A gamma-lactamase from cereal infecting Fusarium spp. catalyses the first step in
      the degradation of the benzoxazolinone class of phytoalexins.
AB  - The benzoxazolinone class of phytoalexins are released by wheat, maize, rye and
      other agriculturally important species in the Poaceae family upon pathogen
      attack. Benzoxazolinones show antimicrobial effects on plant pathogens, but
      certain fungi have evolved mechanisms to actively detoxify these compounds which
      may contribute to the virulence of the pathogens. In many Fusarium spp. a cluster
      of genes is thought to be involved in the detoxification of benzoxazolinones.
      However, only one enzyme encoded in the cluster has been unequivocally assigned a
      role in this process. The first step in the detoxification of benzoxazolinones in
      Fusarium spp. involves the hydrolysis of a cyclic ester bond. This reaction is
      encoded by the FDB1 locus in F. verticillioides but the underlying gene is yet to
      be cloned. We previously proposed that FDB1 encodes a gamma-lactamase, and here
      direct evidence for this is presented. Expression analyses in the important wheat
      pathogen F. pseudograminearum demonstrated that amongst the three predicted gamma
      lactamase genes only the one designated as FDB1, part of the proposed
      benzoxazolinone cluster in F. pseudograminearum, was strongly responsive to
      exogenous benzoxazolinone application. Analysis of independent F.
      pseudograminearum and F. graminearum FDB1 gene deletion mutants, as well as
      biochemical assays, demonstrated that the gamma-lactamase enzyme, encoded by
      FDB1, catalyses the first step in detoxification of benzoxazolinones. Overall,
      our results support the notion that Fusarium pathogens that cause crown rot and
      head blight on wheat have adopted strategies to overcome host-derived chemical
      defences. 

PMID- 26296599
TI  - Distinct roles for the p53-like transcription factor XprG and autophagy genes in
      the response to starvation.
AB  - Autophagy and autolysis are two cannibalistic pathways which allow filamentous
      fungi to obtain nutrients once environmental nutrient sources are exhausted. In
      Aspergillus nidulans, the effects of mutations in two key autophagy genes, atgA,
      the ATG1 ortholog, and atgH, the ATG8 ortholog, were compared with mutations in
      xprG, which encodes a transcriptional activator that plays a key role in
      autolysis. The anti-fungal drug rapamycin induces autophagy in a range of
      organisms. Mutations in atgA and atgH did not alter sensitivity to rapamycin,
      which inhibits growth and asexual spore production (conidiation), indicating that
      autophagy is not required for rapamycin sensitivity in A. nidulans. In contrast,
      inhibition of conidiation by rapamcyin was partially suppressed by the xprG1 gain
      of-function mutation, indicating that XprG acts in the pathway(s) affected by
      rapamycin. It was anticipated that the absence of an intact autophagy pathway
      would accelerate the response to starvation. However, extracellular and
      intracellular protease production in response to carbon or nitrogen starvation
      was not increased in the atgADelta and atgHDelta mutants, and the onset of
      autolysis was not accelerated. Compared to wild-type strains and the xprGDelta
      and xprG1 mutants, conidiation of the autophagy mutants was reduced in carbon- or
      nitrogen-limiting conditions but not during growth on nutrient-sufficient medium.
      Nuclear localization of the global nitrogen regulator AreA in response to
      nitrogen starvation was blocked in the xprG2 loss-of-function mutant, but not in
      the atgHDelta mutant. Conversely, the atgADelta mutation but not the xprGDelta
      mutation prevented vacuolar accumulation of GFP-AtgH, a hallmark of autophagy.
      These results indicate that in A. nidulans there is little interaction between
      autophagy and autolysis and the two pathways are activated in parallel during
      starvation. 

PMID- 26296600
TI  - Detection of dependence patterns with delay.
AB  - The Unitary Events (UE) method is a popular and efficient method used this last
      decade to detect dependence patterns of joint spike activity among simultaneously
      recorded neurons. The first introduced method is based on binned coincidence
      count (Grun, 1996) and can be applied on two or more simultaneously recorded
      neurons. Among the improvements of the methods, a transposition to the continuous
      framework has recently been proposed by Muino and Borgelt (2014) and fully
      investigated by Tuleau-Malot et al. (2014) for two neurons. The goal of the
      present paper is to extend this study to more than two neurons. The main result
      is the determination of the limit distribution of the coincidence count. This
      leads to the construction of an independence test between L>=2 neurons. Finally,
      we propose a multiple test procedure via a Benjamini and Hochberg approach
      (Benjamini and Hochberg, 1995). All the theoretical results are illustrated by a
      simulation study, and compared to the UE method proposed by Grun et al. (2002).
      Furthermore our method is applied on real data. 

PMID- 26296601
TI  - Primary and secondary haemostasis changes related to aging.
AB  - Life expectancy has increased in many countries as a result the world's
      population is aging. The projections indicate that the proportion of the elderly
      in a few decades will increase significantly. Aging carries with it a series of
      physiological changes; one of them is an imbalance in the hemostatic system. Thus
      the levels or activity of various proteins involved, such as most coagulation
      factors, natural anticoagulants and the fibrinolytic system are altered so that
      the hemostatic balance leans toward thrombosis. Also, platelet activity suggests
      a state of abnormal activation (P-selectin, beta thromboglobulin and platelet
      factor). In this review we will systematically examine the alterations in the
      hemostatic components that occur during aging. Therefore, understanding these
      hemostatic changes could contribute to developing strategies for the proper
      management of health in old age. 

PMID- 26296602
TI  - Genetic and biological characterization of two novel reassortant H5N6 swine
      influenza viruses in mice and chickens.
AB  - Novel H5N6 influenza A viruses have infected birds and human beings and caused
      four human clinical cases in China since 2014. The pig, as a mixing vessel, plays
      an important role for influenza virus reassortment and transmission. Towards
      this, routine surveillance for swine influenza in Guangdong province was
      conducted in 2014. In this study, we reported the biological characterization of
      two H5N6 influenza viruses isolated from healthy pigs in Guangdong province.
      Genetic analysis indicates that the two viruses are reassortants of 2.3.4.4 H5N1
      and H6N6 avian influenza viruses with a high similarity to duck and human H5N6
      influenza viruses isolated from Guangdong province. The data from chicken and
      mouse experiments show that the viruses are highly pathogenic in chickens and
      result in a systemic infection, and replicate in the mouse lung accompanying with
      a clinical inflammatory pathology. The results of the study demonstrate that the
      two H5N6 influenza viruses isolated from swine are the avian-originated viruses
      and have not adapted to swine population yet. However, they might keep evolving
      and pose a potential risk to public health and the continued surveillance of
      swine influenza should be strengthened. 

PMID- 26296603
TI  - Multiple-locus variable-number tandem repeat analysis of Leptospira interrogans
      and Leptospira borgpetersenii isolated from small feral and wild mammals in East
      Asia.
AB  - Leptospira spp. are the causative agents of a worldwide zoonosis, leptospirosis,
      maintained by various mammals. Each Leptospira serovar is frequently associated
      with a particular maintenance host, and recently, Leptospira genotype-host
      association has also been suggested to limit serovars to restricted areas. We
      investigated the molecular characteristics of L. interrogans and L.
      borgpetersenii which were isolated from small feral and wild animals in four East
      Asian states using multiple-locus variable-number tandem repeat analysis (MLVA).
      MLVA using 11 loci was performed on 110 L. interrogans serogroups from Japan (79
      strains of 5 serogroups from 3 animal species), Philippines (21; 3; 2), Taiwan
      (7; 2; 3), and Vietnam (3; 1; 1). A MLVA method using 4 loci for L.
      borgpetersenii was established and performed on 52 isolates from Japan (26; 3;
      7), Philippines (13; 1; 2), and Taiwan (13; 1; 3). In L. interrogans, serogroups
      Autumnalis and Hebdomadis appeared more genetically diverse than serogroups
      Bataviae, Grippotyphosa, Icterohaemorrhagiae, Pomona, or Pyrogenes. The former
      serogroup strains with the exception of one Hebdomadis strain were isolated from
      Apodemus speciosus while all the latter serogroup strains with the exception of
      Grippotyphosa were isolated from Rattus norvegicus. L. borgpetersenii was
      isolated from at least 11 animal species while L. interrogans was isolated from
      five species, which might suggest a wider host range for L. borgpetersenii. Broad
      host preference in a single genotype was also observed, which colonized not only
      different species of the same genera but also multiple animal genera. This study
      demonstrates that there may be variability in the range of genetic diversity
      among different Leptospira serogroups, which may be attributed to maintenance
      host animals and environmental factors. 

PMID- 26296604
TI  - Association of genetic polymorphisms in CD8+ T cell inhibitory genes and
      susceptibility to and progression of chronic HBV infection.
AB  - BACKGROUND: Previous studies have shown that multiple inhibitory genes play an
      important role in HBV-specific CD8+ T cell exhaustion and dysfunction in the
      setting of chronic HBV infection. Polymorphic variants of these genes are thought
      to be predisposing factors for HBV susceptibility, clearance, and disease
      progression. The aim of this retrospective study was to identify variants
      affecting chronic HBV infection in a Chinese Han population. METHODS: We chose 28
      tgSNPs from HapMap data on 5 key genes. They were genotyped on a total of 858
      chronic HBV patients, 429 patients who underwent spontaneous recovery, and 239
      healthy controls. We evaluated the correlation between the polymorphisms and HBV
      susceptibility, spontaneous clearance, and disease progression. RESULTS: The
      association of rs3827537 of BIM genotype TA and allele A was significantly
      different (P=0.016, OR=2.049; P=0.031, OR=1.925) between HBV patients and healthy
      controls. The rs36084323 of PD-1, as well as rs3766377, rs485618, rs4656942 of
      CD244 showed significant associations with the risk for HBV-related cirrhosis and
      hepatocellular carcinoma (HCC) (P=0.009, OR=0.482; P=0.009, OR=4.573; P=0.015,
      OR=0.580; P=0.028, OR=2.855). MDR analysis revealed that the four SNPs
      (rs36084323, rs3766377, rs485618, rs4656942) modulated the predisposition to
      cirrhosis and HCC in patients with chronic HBV infection (P=0.006). Using a
      luciferase reporter assay, we demonstrated that various alleles of rs3766377 had
      differential effects, and rs3766377 and rs485618 might have interactive effects.
      CONCLUSIONS: The present study reveals genetic associations among PD-1 and CD244
      variants that may be involved in the development of cirrhosis and HCC in patients
      with chronic HBV infection. The BIM variant was associated with HBV
      susceptibility.

PMID- 26296605
TI  - The Plasmodium gaboni genome illuminates allelic dimorphism of immunologically
      important surface antigens in P. falciparum.
AB  - In the deadly human malaria parasite Plasmodium falciparum, several major
      merozoite surface proteins (MSPs) show a striking pattern of allelic diversity
      called allelic dimorphism (AD). In AD, the vast majority of observed alleles fall
      into two highly divergent allelic classes, with recombinant alleles being rare or
      not observed, presumably due to repression by natural selection (recombination
      suppression, or RS). The three AD loci, merozoite surface proteins (MSPs) 1, 2,
      and 6, along with MSP3, which also exhibits RS among four allelic classes, can be
      collectively called AD/RS. The causes of AD/RS and the evolutionary history of
      allelic diversity at these loci remain mysterious. The few available sequences
      from a single closely related chimpanzee parasite, P. reichenowi, have suggested
      that for 3/4 loci, AD/RS is an ancient state that has been retained in P.
      falciparum since well before the P. falciparum-P. reichenowi ancestor. On the
      other hand, based on comparative sequence analysis, we recently suggested that
      (i) AD/RS P. falciparum loci have undergone interallelic recombination over
      longer evolutionary times (on the timescale of recent speciation events), and
      thus (ii) AD/RS may be a recent phenomenon. The recent publication of genomic
      sequencing efforts for P. gaboni, an outgroup to P. falciparum and P. reichenowi,
      allows for improved reconstruction of the evolutionary history of these loci. In
      this work, I report genic sequence for P. gaboni for all four AD/RS P. falciparum
      loci (MSP1, 2, 3, and 6). Comparison of these sequences with available P.
      falciparum and P. reichenowi data strengthens the evidence for interallelic
      recombination over the evolutionary history of these species and also strengthens
      the case that AD/RS at these loci is ancient. Combined with previous results,
      these data provide evidence that AD/RS at different loci has evolved at several
      different times in the evolutionary history of P. falciparum: (i) before the P.
      gaboni-P. falciparum divergence, for much of MSP1 and MSP3; (ii) between the P.
      gaboni-P. falciparum and P. reichenowi-P. falciparum divergences, for the 5' end
      of the AD region of MSP6 and block 3 of MSP1; (iii) near the P. reichenowi-P.
      falciparum divergence, for the 3' end of the AD region of MSP6; and (iv) after
      the P. reichenowi-P. falciparum divergence, for MSP2. Based on these results, I
      suggest a new hypothesis for long-term evolutionary maintenance of AD/RS by
      recombination within allelic groups. 

PMID- 26296607
TI  - Relative reproductive success of co-infecting parasite genotypes under
      intensified within-host competition.
AB  - In nature, host individuals are commonly simultaneously infected with more than
      one genotype of the same parasite species. These co-infecting parasites often
      interact, which can affect their fitness and shape host-parasite ecology and
      evolution. Many of such interactions take place through competition for limited
      host resources. Therefore, variation in ecological factors modifying the host
      resource level could be important in determining the intensity of competition and
      the outcome of co-infections. We tested this hypothesis by measuring the relative
      reproductive success of co-infecting genotypes of the trematode parasite
      Diplostomum pseudospathaceum in its snail host Lymnaea stagnalis while
      experimentally manipulating snail resource level using contrasting feeding
      treatments (ad libitum food supply, no food). We found that food deprivation
      constrained the overall parasite within-host reproduction as the release of
      parasite transmission stages (cercariae) was reduced. This indicates intensified
      competition among the parasite genotypes. The genotypic composition of the
      released cercariae, however, was not affected by the feeding treatments. This
      suggests that in this system, the relative reproductive success of co-infecting
      parasite genotypes, which is an important component determining their fitness, is
      robust to variation in ecological factors modifying the strength of resource
      competition. 

PMID- 26296606
TI  - Widespread evidence for interspecific mating between Aedes aegypti and Aedes
      albopictus (Diptera: Culicidae) in nature.
AB  - Aedes aegypti and Aedes albopictus, two important vectors of the dengue and
      chikungunya viruses to humans, often come in contact in their invasive ranges. In
      these circumstances, a number of factors are thought to influence their
      population dynamics, including resource competition among the larval stages,
      prevailing environmental conditions and reproductive interference in the form of
      satyrization. As the distribution and abundance of Ae. aegypti and Ae. albopictus
      have profound epidemiological implications, understanding the competitive
      interactions that influence these patterns in nature is important. While evidence
      for resource competition and environmental factors had been gathered from the
      field, the evidence for reproductive interference, though strongly inferred
      through laboratory trials, remained sparse (one small-scale field trial). In this
      paper we demonstrate that low rates (1.12-3.73%) of interspecific mating occur in
      nature among populations of these species that have co-existed sympatrically from
      3 to 150yrs. Finally this report contributes a new species-specific primer set
      for identifying the paternity of sperm extracted from field collected specimens. 

PMID- 26296608
TI  - Otitis media induced by peptidoglycan-polysaccharide (PGPS) in TLR2-deficient
      (Tlr2(-/-)) mice for developing drug therapy.
AB  - BACKGROUND: Toll like receptor 2 (TLR2) signaling can regulate the pathogenesis
      of otitis media (OM). However, the precise role of TLR2 signaling in OM has not
      been clarified due to the lack of an optimal animal model. Peptidoglycan
      polysaccharide (PGPS) of the bacterial cell wall can induce inflammation by
      activating the TLR2 signaling. This study aimed at examining the pathogenic
      characteristics of OM induced by PGPS in Tlr2(-/-) mice, and the potential
      therapeutic effect of sodium aescinate (SA) in this model. METHODS: Wild-type
      (WT) and Tlr2(-/-) mice were inoculated with streptococcal PGPS into their middle
      ears (MEs) and treated intravenously with vehicle or SA daily beginning at 3days
      prior to PGPS for 6 consecutive days. The pathologic changes of individual mice
      were evaluated longitudinally. RESULTS: In comparison with WT mice, Tlr2(-/-)
      mice were susceptible to PGPS-induced OM. Tlr2(-/-) mice displayed greater
      hearing loss, tympanic membrane damage, ME mucosal thickening, longer
      inflammation state, cilia and goblet cell loss. SA-treatment decreased neutrophil
      infiltration, modulated TLR2-related gene expression and improved ciliary
      organization. CONCLUSIONS: PGPS induced a relatively stable OM in Tlr2(-/-) mice,
      providing a new model for OM research. Treatment with SA mitigated the pathogenic
      damage in the ME and may be valuable for intervention of OM.

PMID- 26296609
TI  - "Feeling younger, walking faster": subjective age and walking speed in older
      adults.
AB  - Walking speed is a key vital sign in older people. Given the implications of
      slower gait speed, a large literature has identified health-related, behavioral,
      cognitive, and biological factors that moderate age-related decline in mobility.
      The present study aims to contribute to existing knowledge by examining whether
      subjective age, how old or young individuals experience themselves to be relative
      to their chronological age, contributes to walking speed. Participants were drawn
      from the 2008 and 2012 waves of the Health and Retirement Study (HRS, N = 2970)
      and the 2011 and 2013 waves of the National Health and Aging Trends Study (NHATS,
      N = 5423). In both the HRS and the NHATS, linear regression analysis revealed
      that a younger subjective age was associated with faster walking speed at
      baseline and with less decline over time, controlling for age, sex, education,
      and race. These associations were partly accounted for by depressive symptoms,
      disease burden, physical activity, cognition, body mass index, and smoking.
      Additional analysis revealed that feeling younger than one's age was associated
      with a reduced risk of walking slower than the frailty-related threshold of 0.6
      m/s at follow-up in the HRS. The present study provides novel and consistent
      evidence across two large prospective studies for an association between the
      subjective experience of age and walking speed of older adults. Subjective age
      may help identify individuals at risk for mobility limitations in old age and may
      be a target for interventions designed to mitigate functional decline.

PMID- 26296610
TI  - Disproportionately increased 24-h energy expenditure and fat oxidation in young
      men with low birth weight during a high-fat overfeeding challenge.
AB  - BACKGROUND: Low birth weight (LBW) associates with increased risk of developing
      type 2 diabetes. LBW individuals exhibit disproportionately reduced peripheral
      insulin action and increased fat oxidation after a 5-day high-fat overfeeding
      (HFO) challenge. Furthermore, LBW men exhibit increased nocturnal fat oxidation
      during energy balance and low energy expenditure (EE) during fasting. We
      hypothesized that short-term HFO could further unmask key defects of whole-body
      energy metabolism in LBW men. METHODS: Eighteen LBW (2717 +/- 268 g) and 26
      normal birth weight (NBW) (3893 +/- 207 g) healthy young men were included in a 5
      day HFO (60 E % fat, +50 % calories) study. The 24-h EE, respiratory quotient and
      substrate oxidation rates were assessed by indirect calorimetry using respiratory
      chambers. RESULTS: After adjusting for body composition, the LBW subjects
      displayed increased nighttime EE (P = 0.02) compared with NBW controls during
      HFO. Nighttime glucose oxidation rate was decreased (P = 0.06, adjusted P =
      0.05), while both adjusted 24-h (P = 0.07) and nighttime (P = 0.02) fat oxidation
      rate was elevated in LBW subjects. The relative contribution of fat oxidation to
      EE was increased in LBW compared with NBW men during the entire 24-h period (P =
      0.06) and during nighttime (P = 0.03). CONCLUSIONS: We suggest that
      disproportionally enhanced fat oxidation in LBW individuals during short-term HFO
      represents a compensatory response to reduced subcutaneous adipose tissue
      expandability and storage capacity. The extent to which this mechanism may lead
      to, or be replaced by insulin resistance, ectopic fat accumulation and/or glucose
      intolerance during long-term HFO in LBW needs further studies.

PMID- 26296611
TI  - [Verrucous tumor at the ankle of a 68-year-old man].

PMID- 26296612
TI  - Purification and functional characterization of thermostable 5-aminolevulinic
      acid synthases.
AB  - OBJECTIVES: As 5-aminolevulinic acid synthase (ALAS), the key enzyme for 5
      aminolevulinic acid (ALA) synthesis, is unstable, we have sought to find
      thermostable ALASs from thermophilic organisms. RESULTS: Three ALASs from
      thermophiles Geobacillus thermoglucosidasius (GT-ALAS), Laceyella sacchari (LS
      ALAS) and Pseudomonas alcaliphila (PA-ALAS) were purified and characterized. All
      enzymes were more stable than two previously studied ALASs from Rhodopseudomonas
      palustris and Rhodobacter sphaeroides. There was almost no activity change after
      60 h at 37  degrees C for the three thermostable enzymes. This contrasts with the
      other two enzymes which lost over 90 % activities in just 1 h. Furthermore, the
      specific activity of LS-ALAS (7.8 U mg(-1)) was also higher than any previously
      studied ALASs. CONCLUSIONS: Thermostable ALASs were found in thermophilic
      organisms and this paves the way for developing cell free processes for enzymatic
      production of ALA from bulk chemicals succinate and glycine.

PMID- 26296613
TI  - The correlation between the metabolic tumor volume and hematological parameters
      in patients with esophageal cancer.
AB  - INTRODUCTION: The aim of this study is to evaluate the correlation of the serum
      neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and mean
      platelet volume (MPV), with the standardized uptake value (SUVmax), and metabolic
      tumor volume (MTV) in F-18 fluorodeoxyglucose (FDG) positron emission
      tomography/computed tomography (PET/CT) in patient with esophageal squamous cell
      cancer at baseline. METHODS: PET/CTs were performed in 52 patients with
      esophageal squamous cell cancer, making up the patient group. An additional 52
      patients who underwent endoscopy due to dyspepsia with normal esophagus (as a
      control group) were included in the study to compare the hematological parameters
      between the patient groups. RESULTS: The median age was 60.0 +/- 12.8 years
      (range 39-84 years) for the patients with esophageal cancer, and 56.9 +/- 12.3
      years for the control group. Statistical differences were found in terms of the
      neutrophils, lymphocytes, NLR, PLT, PLR, and MPV between the patients with
      esophageal cancer and the control group. In the correlation analysis, only the
      NLR was correlated with the MTV for all of the patients (p = 0.013, r = 0.344).
      The SUVmax was not correlated with these hematological parameters. CONCLUSION: At
      baseline neutrophil-to-lymphocyte ratio is associated with the metabolic tumor
      volume, which was assessed using the PET/CT in patients with esophageal squamous
      cell cancer. The SUVmax values were not related to these parameters.

PMID- 26296615
TI  - The role of temporal speech cues in facilitating the fluency of adults who
      stutter.
AB  - PURPOSE: Adults who stutter speak more fluently during choral speech contexts
      than they do during solo speech contexts. The underlying mechanisms for this
      effect remain unclear, however. In this study, we examined the extent to which
      the choral speech effect depended on presentation of intact temporal speech cues.
      We also examined whether speakers who stutter followed choral signals more
      closely than typical speakers did. METHOD: 8 adults who stuttered and 8 adults
      who did not stutter read 60 sentences aloud during a solo speaking condition and
      three choral speaking conditions (240 total sentences), two of which featured
      either temporally altered or indeterminate word duration patterns. Effects of
      these manipulations on speech fluency, rate, and temporal entrainment with the
      choral speech signal were assessed. RESULTS: Adults who stutter spoke more
      fluently in all choral speaking conditions than they did when speaking solo. They
      also spoke slower and exhibited closer temporal entrainment with the choral
      signal during the mid- to late-stages of sentence production than the adults who
      did not stutter. Both groups entrained more closely with unaltered choral signals
      than they did with altered choral signals. CONCLUSIONS: Findings suggest that
      adults who stutter make greater use of speech-related information in choral
      signals when talking than adults with typical fluency do. The presence of fluency
      facilitation during temporally altered choral speech and conversation babble,
      however, suggests that temporal/gestural cueing alone cannot account for fluency
      facilitation in speakers who stutter. Other potential fluency enhancing
      mechanisms are discussed. EDUCATIONAL OBJECTIVES: The reader will be able to (a)
      summarize competing views on stuttering as a speech timing disorder, (b) describe
      the extent to which adults who stutter depend on an accurate rendering of
      temporal information in order to benefit from choral speech, and (c) discuss
      possible explanations for fluency facilitation in the presence of inaccurate or
      indeterminate temporal cues.

PMID- 26296614
TI  - Early Traumatic Stress Responses in Parents Following a Serious Illness in Their
      Child: A Systematic Review.
AB  - A systematic review of the literature investigating the early traumatic stress
      responses in parents of children diagnosed with a serious illness/injury. A
      literature review was conducted (September 2013) using Medline, PsycINFO, and
      CINAHL databases. Twenty-four studies related to parents of children hospitalized
      due to diagnosis of cancer, type 1 diabetes, meningococcal disease, trauma or
      serious injury, preterm birth and other serious illnesses requiring admission to
      intensive care were included. Parents were assessed for early traumatic stress
      symptoms within 3 months of their child's diagnosis/hospitalization. Prevalence
      rates of acute stress disorder in parents ranged from 12 to 63%. Prevalence of
      posttraumatic stress disorder ranged from 8 to 68%. Variability was related to
      methodological factors including differences in study design, timing of
      assessments, measurement tools, and scoring protocols. Psychosocial factors
      rather than medical factors predicted parent distress. This review integrates and
      compares early traumatic reactions in parents with children suffering a range of
      serious illnesses. Findings suggest a high prevalence of acute and posttraumatic
      stress symptoms in parents. Methodological inconsistencies made comparison of
      early traumatic stress prevalence rates difficult. Risk factors associated with
      traumatic stress symptoms were identified.

PMID- 26296616
TI  - Sympathetic arousal of young children who stutter during a stressful picture
      naming task.
AB  - PURPOSE: The purpose of the current study was to investigate sympathetic arousal
      of young children who do and do not stutter during a stressful picture-naming
      task under instructions to name pictures as rapidly as possible. METHOD: Thirty
      seven young children who stutter (CWS) and 39 young children who do not stutter
      (CWNS) served as participants. Dependent measures consisted of tonic skin
      conductance during a pretask baseline, a stress-inducing rapid picture-naming
      task, and post-picture-naming task condition. RESULTS: Findings indicated that,
      when chronological age was not taken into account, there was no between-group
      difference in tonic skin conductance level. When age was taken into account,
      however, there was a significant talker group*age group interaction, with follow
      up analyses indicating that 3-year-old CWS exhibited significantly higher
      sympathetic arousal than their CWNS peers, and their 4-year-old CWNS peers.
      CONCLUSIONS: Findings were taken to be consistent with non-physiological results
      indicating an association between emotional processes and childhood stuttering.
      This association, at least for this cross-sectional study of tonic skin
      conductance level (SCL) during a picture-naming task, was moderated by children's
      chronological age. Such developmental differences may be associated with various
      processes, for example, attention, cognition, or physiology, or some combination
      of two or more of these processes. Future empirical study of these processes in
      young CWS and CWNS may profit from longitudinal measurement of converging lines
      of evidence from behavioral, parent and psychophysiological indexes of emotional
      reactivity and regulation. EDUCATIONAL OBJECTIVES: After reading this article,
      the reader will be able to: (a) discuss salient findings in the literature
      regarding the association between emotional processes and childhood stuttering;
      (b) discuss sympathetic arousal, and how skin conductance is used to measure it;
      and (c) discuss the role of chronological age in the association between emotion
      and stuttering in young children.

PMID- 26296618
TI  - How Should We Estimate the Cost-effectiveness of Interventions That Affect
      Reproduction?

PMID- 26296617
TI  - ADAM10 and BACE1 are localized to synaptic vesicles.
AB  - Synaptic degeneration and accumulation of the neurotoxic amyloid beta-peptide
      (Abeta) in the brain are hallmarks of Alzheimer disease. Abeta is produced by
      sequential cleavage of the amyloid precursor protein (APP), by the beta-secretase
      beta-site APP cleaving enzyme 1 (BACE1) and gamma-secretase. However, Abeta
      generation is precluded if APP is cleaved by the alpha-secretase ADAM10 instead
      of BACE1. We have previously shown that Abeta can be produced locally at the
      synapse. To study the synaptic localization of the APP processing enzymes we used
      western blotting to demonstrate that, compared to total brain homogenate, ADAM10
      and BACE1 were greatly enriched in synaptic vesicles isolated from rat brain
      using controlled-pore glass chromatography, whereas Presenilin1 was the only
      enriched component of the gamma-secretase complex. Moreover, we detected ADAM10
      activity in synaptic vesicles and enrichment of the intermediate APP-C-terminal
      fragments (APP-CTFs). We confirmed the western blotting findings using in situ
      proximity ligation assay to demonstrate close proximity of ADAM10 and BACE1 with
      the synaptic vesicle marker synaptophysin in intact mouse primary hippocampal
      neurons. In contrast, only sparse co-localization of active gamma-secretase and
      synaptophysin was detected. These results indicate that the first step of APP
      processing occurs in synaptic vesicles whereas the final step is more likely to
      take place elsewhere.

PMID- 26296619
TI  - Improving Medical Decision Making and Health Promotion through Culture-Sensitive
      Health Communication: An Agenda for Science and Practice.
AB  - This review introduces the concept of culture-sensitive health communication. The
      basic premise is that congruency between the recipient's cultural characteristics
      and the respective message will increase the communication's effectiveness.
      Culture-sensitive health communication is therefore defined as the deliberate and
      evidence-informed adaptation of health communication to the recipients' cultural
      background in order to increase knowledge and improve preparation for medical
      decision making and to enhance the persuasiveness of messages in health
      promotion. To achieve effective health communication in varying cultural
      contexts, an empirically and theoretically based understanding of culture will be
      indispensable. We therefore define culture, discuss which evolutionary and
      structural factors contribute to the development of cultural diversity, and
      examine how differences are conceptualized as scientific constructs in current
      models of cultural differences. In addition, we will explicate the implications
      of cultural differences for psychological theorizing, because common constructs
      of health behavior theories and decision making, such as attitudes or risk
      perception, are subject to cultural variation. In terms of communication, we will
      review both communication strategies and channels that are used to disseminate
      health messages, and we will discuss the implications of cultural differences for
      their effectiveness. Finally, we propose an agenda both for science and for
      practice to advance and apply the evidence base for culture-sensitive health
      communication. This calls for more interdisciplinary research between science and
      practice but also between scientific disciplines and between basic and applied
      research.

PMID- 26296620
TI  - Can I Count on Getting Better? Association between Math Anxiety and Poorer
      Understanding of Medical Risk Reductions.
AB  - BACKGROUND: Lower numerical ability is associated with poorer understanding of
      health statistics, such as risk reductions of medical treatment. For many people,
      despite good numeracy skills, math provokes anxiety that impedes an ability to
      evaluate numerical information. Math-anxious individuals also report less
      confidence in their ability to perform math tasks. We hypothesized that,
      independent of objective numeracy, math anxiety would be associated with poorer
      responding and lower confidence when calculating risk reductions of medical
      treatments. METHODS: Objective numeracy was assessed using an 11-item objective
      numeracy scale. A 13-item self-report scale was used to assess math anxiety. In
      experiment 1, participants were asked to interpret the baseline risk of disease
      and risk reductions associated with treatment options. Participants in experiment
      2 were additionally provided a graphical display designed to facilitate the
      processing of math information and alleviate effects of math anxiety. Confidence
      ratings were provided on a 7-point scale. RESULTS: Individuals of higher
      objective numeracy were more likely to respond correctly to baseline risks and
      risk reductions associated with treatment options and were more confident in
      their interpretations. Individuals who scored high in math anxiety were instead
      less likely to correctly interpret the baseline risks and risk reductions and
      were less confident in their risk calculations as well as in their assessments of
      the effectiveness of treatment options. Math anxiety predicted confidence levels
      but not correct responding when controlling for objective numeracy. The graphical
      display was most effective in increasing confidence among math-anxious
      individuals. CONCLUSIONS: The findings suggest that math anxiety is associated
      with poorer medical risk interpretation but is more strongly related to
      confidence in interpretations.

PMID- 26296621
TI  - Growth hormone and the risk of atherosclerosis in growth hormone-deficient
      children.
AB  - OBJECTIVE: Growth hormone-deficient (GHD) children have been found to have higher
      cardiovascular mortality rates and an increased carotid intima-media thickness
      (CIMT). This study investigated the risk of atherosclerosis and the effect of
      recombinant growth hormone (rhGH) replacement therapy on the lipid profile and
      CIMT in GHD children. DESIGN: A total of 40 GHD children (mean age: 12.3+/-2.04
      years) were investigated before and after 1 year of rhGH therapy at a dosage of
      0.03 mg/kg/day and 40 age- and sex-matched healthy children (mean age: 12.1+/
      2.23 years) were enrolled as a control group, in the same pubertal stage. Fasting
      blood samples were obtained for lipid profile, IGF-1, and IGFBP-3 analyses. The
      patients and controls underwent CIMT measurements before and after 1 year of rhGH
      treatment. RESULTS: The growth velocity and height standard deviation scores
      increased significantly over 1 year of treatment in all patients. The total
      cholesterol (TC), low-density lipoprotein (LDL) cholesterol, and atherogenic
      index (Ai) values were increased while the high-density lipoprotein (HDL)
      cholesterol value was decreased in the GHD children, as compared to the controls;
      however, the triglyceride (TG) level was comparable. After 1 year of treatment, a
      significant decrease in the TC, LDL cholesterol, and Ai values as well as a
      significant increase in the HDL value were observed in the GHD patients, with the
      values becoming similar to those in the control group. The mean CIMT was
      significantly greater in the GHD subjects than in the controls. After 1 year of
      therapy, the CIMT in the GHD subjects had decreased significantly; however, it
      was still greater than that in the control group. IGF-1 was negatively correlated
      with TC, LDL cholesterol, Ai, right CIMT, and left CIMT. CONCLUSIONS: GHD is
      associated with increased atherosclerotic risk in children. An improved lipid
      profile and CIMT were detected after 1 year of hormone replacement therapy.

PMID- 26296623
TI  - Comparative analysis of decision maker preferences for equity/efficiency
      attributes in reimbursement decisions in three European countries.
AB  - BACKGROUND: In addition to cost-effectiveness, national guidelines often include
      other factors in reimbursement decisions. However, weights attached to these are
      rarely quantified, thus decisions can depend strongly on decision-maker
      preferences. OBJECTIVE: To explore the preferences of policymakers and healthcare
      professionals involved in the decision-making process for different efficiency
      and equity attributes of interventions and to analyse cross-country differences.
      METHOD: Discrete choice experiments (DCEs) were carried out in Austria, Hungary,
      and Norway with policymakers and other professionals working in the health
      industry (N = 153 respondents). Interventions were described in terms of
      different efficiency and equity attributes (severity of disease, target age of
      the population and willingness to subsidise others, potential number of
      beneficiaries, individual health benefit, and cost-effectiveness). Parameter
      estimates from the DCE were used to calculate the probability of choosing a
      healthcare intervention with different characteristics, and to rank different
      equity and efficiency attributes according to their importance. RESULTS: In all
      three countries, cost-effectiveness, individual health benefit and severity of
      the disease were significant and equally important determinants of decisions. All
      countries show preferences for interventions targeting young and middle aged
      populations compared to those targeting populations over 60. However, decision
      makers in Austria and Hungary show preferences more oriented to efficiency than
      equity, while those in Norway show equal preferences for equity and efficiency
      attributes. CONCLUSION: We find that factors other than cost-effectiveness seem
      to play an equally important role in decision-making. We also find evidence of
      cross-country differences in the weight of efficiency and equity attributes.

PMID- 26296622
TI  - Strong expression of polypeptide N-acetylgalactosaminyltransferase 3
      independently predicts shortened disease-free survival in patients with early
      stage oral squamous cell carcinoma.
AB  - The polypeptide N-acetylgalactosaminyltransferase (GalNAc-Ts) family of enzymes
      regulates the critical initial steps of mucin-type O-glycosylation. Among GalNAc
      Ts that may significantly influence cancer biology, thus affecting cell
      differentiation, adhesion, invasion, and/or metastasis, GalNAc-T3 exhibits a high
      expression in several human cancers, closely associated with tumor progression
      and a poor prognosis. However, the expression pattern of GalNAc-T3 in oral
      squamous cell carcinoma (OSCC) remains obscure. Since postoperative recurrence of
      even early stage OSCC (ESOSCC) occurs at an early phase, significantly affecting
      their clinical course and worse outcome, the identification of clinically
      significant accurate biomarkers is needed. Therefore, we investigated the
      correlation between the immunohistochemical GalNAc-T3 expression and various
      clinicopathological characteristics and recurrence using 110 paraffin-embedded
      tumor samples obtained from patients with surgically resected ESOSCC (T1-2N0).
      Recurrence was recognized in 37 of 110 (33.6 %) patients. The GalNAc-T3
      expression was considered to be strongly positive when 20 % or more of the cancer
      cells showed positive cytoplasmic staining. Consequently, a strong expression of
      GalNAc-T3 was observed in 40 patients (36.4 %), showing a close relationship to
      poor differentiation, the presence of lymphatic and vascular invasion, and
      recurrence. Univariate and multivariate analyses further demonstrated that the
      patients with a strong GalNAc-T3+ status had markedly lower disease-free survival
      (DFS) rates, especially within the first 2 years postoperatively. Therefore,
      GalNAc-T3 might play a role in the pathogenesis of ESOSCC recurrence, and its
      immunohistochemical detection potentially predicts a shorter DFS and may be a
      useful parameter for providing clinical management against ESOSCC in the early
      postoperative phase. 

PMID- 26296624
TI  - Electrostatic dust collectors compared to inhalable samplers for measuring
      endotoxin concentrations in farm homes.
AB  - Paired electrostatic dust collectors (EDCs) and daily, inhalable button samplers
      (BS) were used concurrently to sample endotoxin in 10 farm homes during 7-day
      periods in summer and winter. Winter sampling included an optical particle
      counter (OPC) to measure PM2.5 and PM2.5-10 . Electrostatic dust collectors and
      BS filters were analyzed for endotoxin using the kinetic chromogenic Limulus
      amebocyte lysate assay. Optical particle counter particulate matter (PM) data
      were divided into two PM categories. In summer, geometric mean (geometric
      standard deviation) endotoxin concentrations were 0.82 EU/m(3) (2.7) measured
      with the BS and 737 EU/m(2) (1.9) measured with the EDC. Winter values were 0.52
      EU/m(3) (3.1) for BS and 538 EU/m(2) (3.0) for EDCs. Seven-day endotoxin values
      of EDCs were highly correlated with the 7-day BS sampling averages (r = 0.70; P <
      0.001). Analysis of variance indicated a 2.4-fold increase in EDC endotoxin
      concentrations for each unit increase of the ratio of PM2.5 to PM2.5-10 . There
      was also a significant correlation between BS and EDCs endotoxin concentrations
      for winter (r = 0.67; P < 0.05) and summer (r = 0.75; P < 0.05). Thus, EDCs
      sample comparable endotoxin concentrations to BS, making EDCs a feasible, easy to
      use alternative to BS for endotoxin sampling.

PMID- 26296625
TI  - Microdomain Formation Controls Spatiotemporal Dynamics of Cell-Surface
      Glycoproteins.
AB  - The effect of galectin-mediated microdomain formation on the spatiotemporal
      dynamics of glycosylated membrane proteins in human microvascular endothelial
      cells (HMEC-1) was studied qualitatively and quantitatively by high-resolution
      fluorescence microscopy and artificially mimicked by metabolic glycoprotein
      engineering. Two types of membrane proteins, sialic acid-bearing proteins (SABPs)
      and mucin-type proteins (MTPs), were investigated. For visualization they were
      metabolically labeled with azido sugars and then coupled to a cyclooctyne
      conjugated fluorescent dye by click chemistry. Both spatial (diffusion) and
      temporal (residence time) dynamics of SABPs and MTPs on the membrane were
      investigated after treatment with exogenous galectin-1 or -3. Strong effects of
      galectin-mediated lattice formation were observed for MTPs (decreased spatial
      mobility), but not for SABPs. Lattice formation also strongly decreased the
      turnover of MTPs (increased residence time on the cell membrane). The effects of
      galectin-mediated crosslinking was accurately mimicked by streptavidin-mediated
      crosslinking of biotin-tagged glycoproteins and verified by single-molecule
      tracking. This technique allows the induction of crosslinking of membrane
      proteins under precisely controlled conditions, thereby influencing membrane
      residence time and the spatial dynamics of glycans on the cell membrane in a
      controlled way. 

PMID- 26296626
TI  - [On the evolution of scientific thought].
AB  - The Nominalists of the XIV century, precursors of modern science, thought that
      science's object was not the general, vague and indeterminate but the particular,
      which is real and can be known directly. About the middle of the XVII Century the
      bases of the modern science became established thanks to a revolution fomented
      essentially by Galileo, Bacon and Descartes. During the XVIII Century, parallel
      to the development of the great current of English Empiricism, a movement of
      scientific renewal also arose in continental Europe following the discipline of
      the Dutch Physicians and of Boerhaave. In the XIX Century, Claude Bernard
      dominated the scientific medicine but his rigorous determinism impeded him from
      taking into account the immense and unforeseeable field of the random. Nowadays,
      we approach natural science and medicine, from particular groups of facts; that
      is, from the responses of Nature to specific questions, but not from the general
      laws. Furthermore, in recent epistemology, the concept that experimental data are
      not pure facts, but rather, facts interpreted within a hermeneutical context has
      been established. Finally a general tendency to retrieve philosophical questions
      concerning the understanding of essence and existence can frequently be seen in
      scientific inquiry. In the light of the evolution of medical thought, it is
      possible to establish the position of scientific medicine within the movement of
      ideas dominating in our time. 

PMID- 26296628
TI  - Mouse Models of Acute Respiratory Distress Syndrome: A Review of Analytical
      Approaches, Pathologic Features, and Common Measurements.
AB  - Acute respiratory distress syndrome (ARDS) is a severe pulmonary reaction
      requiring hospitalization, which is incited by many causes, including bacterial
      and viral pneumonia as well as near drowning, aspiration of gastric contents,
      pancreatitis, intravenous drug use, and abdominal trauma. In humans, ARDS is very
      well defined by a list of clinical parameters. However, until recently no
      consensus was available regarding the criteria of ARDS that should be evident in
      an experimental animal model. This lack was rectified by a 2011 workshop report
      by the American Thoracic Society, which defined the main features proposed to
      delineate the presence of ARDS in laboratory animals. These should include
      histological changes in parenchymal tissue, altered integrity of the alveolar
      capillary barrier, inflammation, and abnormal pulmonary function. Murine ARDS
      models typically are defined by such features as pulmonary edema and leukocyte
      infiltration in cytological preparations of bronchoalveolar lavage fluid and/or
      lung sections. Common pathophysiological indicators of ARDS in mice include
      impaired pulmonary gas exchange and histological evidence of inflammatory
      infiltrates into the lung. Thus, morphological endpoints remain a vital component
      of data sets assembled from animal ARDS models. 

PMID- 26296627
TI  - Body weight gain in patients with bilateral deep brain stimulation for dystonia.
AB  - In patients with Parkinson's disease, significant weight gain following chronic
      deep brain stimulation (DBS) has been reported. Recently, relevant weight gain
      could be demonstrated also following subthalamic nucleus DBS in patients with
      primary cervical dystonia. Prospective analyses of body weight changes following
      DBS in patients with dystonia, however, have not been published so far. We aimed
      to analyse the changes of body weight following DBS in patients with dystonia.
      The body mass index (BMI) of 17 consecutive patients with segmental or
      generalised dystonia (mean age 54.6 +/- 16.1 years) treated with bilateral DBS of
      the globus pallidus internus (GPi) (n = 14) or the thalamic ventral intermediate
      nucleus (n = 3) was measured preoperatively (pre-OP) and at three follow-up (FU)
      time points post-DBS surgery (FU1 = 7 months, FU2 = 17 months, FU3 = 72 months).
      All patients benefited from marked improvement in their dystonia. The mean BMI
      pre-OP (SD) was 22.5 (+/-3.7) kg/m(2) and increased stepwise to 24.0 (+/-3.3)
      kg/m(2) at FU1, 24.4 (+/-3.7) kg/m(2) at FU2 and 24.9 (+/-3.7) kg/m(2) at FU3 (p
      < 0.05 at all three FUs compared to pre-OP). Relative BMI increase and
      improvement of dystonia were correlated (p = 0.025). Chronic bilateral GPi DBS in
      patients with dystonia is associated with significant body weight gain, in
      particular during the first 6 months post-OP. This probably is a result of
      improvement of dystonic motor symptoms and recovery of eating dysfunction rather
      than a target-specific phenomenon. 

PMID- 26296629
TI  - Regulatory Forum Opinion Piece: Carcinogen Risk Assessment: The Move from Screens
      to Science.
AB  - Throughout the last 50 years, the paradigm for carcinogenicity assessment has
      depended on lifetime bioassays in rodents. Since 1997, the International
      Conference on Harmonisation (ICH) S1B has permitted the use of a 2-year rodent
      bioassay (usually in the rat) and an alternative, genetically modified mouse
      model to support cancer risk assessment of pharmaceuticals. Since its
      introduction, it has become apparent that many of the stated advantages of the 6
      month Tg mouse bioassay have, in actual fact, not been realized, and the concern
      exists that an albeit imperfect, 2-year mouse bioassay has been replaced by a
      similarly imperfect 6-month equivalent. This essay argues strongly that model
      systems, using cancer as the end point, should be discontinued, and that the
      recent initiatives, from the Organization for Economic Cooperation and
      Development and Institute of Peace and Conflict Studies, on "mode of action,"
      "adverse outcome pathways," and "human relevance framework" should be embraced as
      being risk assessments based upon the available science. The recent suggested
      revisions to the ICH S1 guidelines, utilizing carcinogenicity assessment
      documents, go some way to developing a science-based risk assessment that does
      not depend almost entirely on a single, imperfect, cancer-based end point in
      nonrelevant animal species. 

PMID- 26296630
TI  - Long-term Local and Systemic Safety of Poly(L-lactide-co-epsilon-caprolactone)
      after Subcutaneous and Intra-articular Implantation in Rats.
AB  - The use of biodegradable materials is gaining popularity in medicine, especially
      in orthopedic applications. However, preclinical evaluation of biodegradable
      materials can be challenging, since they are located in close contact with host
      tissues and might be implanted for a long period of time. Evaluation of these
      compounds requires biodegradability and biocompatibility studies and meticulous
      pathology examination. We describe 2 preclinical studies performed on Sprague
      Dawley rats for 52 weeks, to evaluate clinical pathology, biocompatibility,
      biodegradability, and systemic toxicity after implantation of 2-layered films or
      saline-inflated balloon-shaped implants of downsized InSpaceTM devices (termed
      "test device"). The test devices are made from a copolymer of poly-L-lactide-co-?
      caprolactone in a 70:30 ratio, identical to the device used in humans, intended
      for the treatment of rotator cuff tears. Intra-articular film implantation and
      subcutaneous implantation of the downsized device showed favorable local and
      systemic tolerability. Although the implanted materials have no inherent toxic or
      tumorigenic properties, one animal developed a fibrosarcoma at the implantation
      site, an event that is associated with a rodent-predilection response where solid
      materials cause mesenchymal neoplasms. This effect is discussed in the context of
      biodegradable materials along with a detailed description of expected pathology
      for biodegradable materials in long-term rodent studies.

PMID- 26296631
TI  - Recommended Methods for Brain Processing and Quantitative Analysis in Rodent
      Developmental Neurotoxicity Studies.
AB  - Neuropathology methods in rodent developmental neurotoxicity (DNT) studies have
      evolved with experience and changing regulatory guidance. This article emphasizes
      principles and methods to promote more standardized DNT neuropathology
      evaluation, particularly procurement of highly homologous brain sections and
      collection of the most reproducible morphometric measurements. To minimize bias,
      brains from all animals at all dose levels should be processed from brain
      weighing through paraffin embedding at one time using a counterbalanced design.
      Morphometric measurements should be anchored by distinct neuroanatomic landmarks
      that can be identified reliably on the faced block or in unstained sections and
      which address the region-specific circuitry of the measured area. Common test
      article-related qualitative changes in the developing brain include abnormal cell
      numbers (yielding altered regional size), displaced cells (ectopia and
      heterotopia), and/or aberrant differentiation (indicated by defective myelination
      or synaptogenesis), but rarely glial or inflammatory reactions. Inclusion of
      digital images in the DNT pathology raw data provides confidence that the
      quantitative analysis was done on anatomically matched (i.e., highly homologous)
      sections. Interpreting DNT neuropathology data and their presumptive correlation
      with neurobehavioral data requires an integrative weight-of-evidence approach
      including consideration of maternal toxicity, body weight, brain weight, and the
      pattern of findings across brain regions, doses, sexes, and ages. 

PMID- 26296632
TI  - Exploring Perceptions of Early-Career Psychiatrists About Their Relationships
      With the Pharmaceutical Industry.
AB  - OBJECTIVES: The pharmaceutical industry has engaged physicians through medical
      education, patient care, and medical research. New conflict of interest policy
      has highlighted the challenges to these relationships. The objective of this
      study was to explore the perceptions that early career psychiatrists (e.g. those
      within 5 years of entering practice) have regarding their relationship with the
      pharmaceutical industry. METHODS: Data were collected through semi-structured
      interviews and were analysed using a grounded theory methodology. Interviews were
      conducted and analyzed in an iterative way using a constant comparison approach
      in which data were collected and open coded for themes and subthemes. As new
      interviews were conducted, the themes were applied to data along with emergent
      themes and previous interviews recoded until additional interviews failed to
      provide new themes and thematic saturation was achieved. Through axial coding, a
      process of relating codes (categories and concepts) to each other, the theory was
      generated to explain the core variable mediating perceptions participants had
      about the relationship with industry. RESULTS: The participants described
      increasing frequency of experiences with industry throughout training into
      practice. Their perceptions developed through training, physician culture,
      industry promotion, and their own practices. In managing the relationship with
      industry, participants would either avoid interactions or engage in behaviors
      aimed to reduce the risk of influence. Maintaining one's professional integrity
      was the underlying driver used to manage the relationship with industry.
      CONCLUSIONS: Psychiatrists develop perceptions about industry through experience
      and observation leading them to develop their own strategies to manage these
      relationships while maintaining their professional integrity.

PMID- 26296633
TI  - Maternal nutrition during pregnancy and risk of asthma, wheeze, and atopic
      diseases during childhood: a systematic review and meta-analysis.
AB  - BACKGROUND: Epidemiologic studies suggest a relationship between maternal
      nutrition during pregnancy and the occurrence of asthma and atopic conditions
      during childhood. However, individual study results are conflicting. The
      objective of this meta-analysis was to critically examine the current evidence
      for an association between nutrition (dietary patterns, food groups, vitamins, or
      oligo-elements) ingestion during pregnancy and asthma, wheeze, or atopic
      conditions in childhood. METHODS: The inclusion criteria were as follows: (i)
      systematic recording of diet during the gestational period and (ii) documentation
      of asthma, wheezing, eczema, or other atopic disease in the offspring. The
      primary outcomes were prevalence of asthma or wheeze among the offspring during
      childhood; and secondary outcomes were prevalence of eczema, allergic rhinitis,
      or other atopic conditions. RESULTS: We found 120 titles, abstracts, and
      citations, and 32 studies (29 cohorts) were included in this analysis. Data on
      vitamins, oligo-elements, food groups, and dietary patterns during pregnancy were
      collected. A meta-analysis revealed that higher maternal intake of vitamin D
      [odds ratio (OR) = 0.58, 95% confidence interval (CI) = 0.38-0.88], vitamin E (OR
      = 0.6, 95% CI = 0.46-0.78), and zinc (OR = 0.62, 95% CI = 0.40-0.97) was
      associated with lower odds of wheeze during childhood. However, none of these or
      other nutrients was consistently associated with asthma per se or other atopic
      conditions. CONCLUSIONS: Current evidence suggests a protective effect of
      maternal intake of each of three vitamins or nutrients (vitamin D, vitamin E, and
      zinc) against childhood wheeze but is inconclusive for an effect on asthma or
      other atopic conditions.

PMID- 26296634
TI  - Comparison of humeral rotation co-activation of breast cancer population and
      healthy shoulders.
AB  - Upper limb morbidities are common amongst the breast cancer population (BCP) and
      have a direct impact on independence. Comparing muscle co-activation strategies
      between BCP and healthy populations may assist in identifying muscle dysfunction
      and promote clinical interpretation of dysfunction, which could direct
      preventative and therapeutic interventions. The purposes of this study were to
      define humeral rotation muscle co-activation of a BCP and to compare it with a
      previously defined co-activation relationship of a healthy population. Fifty BCP
      survivors performed 18 isometric internal and external rotation exertions at
      various postures and intensities. Surface and intramuscular electrodes recorded
      shoulder muscle activity. BCP co-activation was predicted at r(2)=0.77 during
      both exertion types. Humeral abduction angle and task intensity were important
      factors in the prediction of co-activation in both populations. Comparisons made
      between populations identified differing muscle strategies used by BCP to
      maintain postural control. Compared to healthy co-activation, the BCP
      demonstrated greater activation of internal (IR) and external rotator (ER) type
      muscles during their respective rotation type. The BCP demonstrated increased
      (?8.7%) activation of pectoralis major. This study has provided insight into how
      BCP muscles compensate during dysfunction. Continued advancement of this
      knowledge can provide more understanding of dysfunction, promote generation of
      evidence-based therapies, and can be useful in biomechanical modeling. 

PMID- 26296635
TI  - Analysis of Characteristics Similar to Autoimmune Disease in Keloid Patients.
AB  - BACKGROUND: Keloid is a fibrotic skin disease for which immune cell infiltration
      is a primary pathological hallmark. Meanwhile, in autoimmune diseases, triggering
      of the inflammation response can lead to tissue injury and subsequent organ
      fibrosis. When the skin is involved in autoimmune disease, skin fibrosis such as
      that seen in scleroderma can occur. In this study, we propose that keloid
      possesses features of autoimmune disease. METHODS: To verify whether keloid
      possesses features of autoimmune disease, immune cell infiltration and immune
      complex deposits were detected with immunohistochemical staining and
      immunofluorescence, respectively, in keloid and normal skin tissues. A routine
      antinuclear antibody profile was tested in sera from 28 keloid patients and 28
      healthy controls. Lastly, the anti-hnRNPA2B1 autoantibody in sera was evaluated
      by enzyme-linked immunosorbent assay. RESULTS: The numbers of CD1alpha(+)
      Langerhans cells, CD3(+) T lymphocytes, CD68(+) macrophages, and CD20(+) B
      lymphocytes increased in keloid tissues compared to normal skin. IgA, IgM, C3,
      and C1q deposits were found in keloid tissues but not in normal skin, while anti
      hnRNPA2B1 levels in sera from keloid patients were elevated. CONCLUSION: The
      above findings suggest that keloids have some characteristics that are similar to
      autoimmune disease and might be mediated by autoimmune responses. LEVEL OF
      EVIDENCE IV: This journal requires that authors assign a level of evidence to
      each article. For a full description of these Evidence-Based Medicine ratings,
      please refer to the Table of Contents or the online Instructions to Authors
      www.springer.com/00266 .

PMID- 26296636
TI  - A Comparison Between Two Methods of Face-Lift Surgery in Nine Cadavers: SMAS
      (Superficial Musculo-Aponeurotic System) Versus MACS (Minimal Access Cranial
      Suspension).
AB  - BACKGROUND: This study aimed to compare the average amounts of facial skin and
      muscle lifting in two different face-lift methods, superficial musculo
      aponeurotic system (SMAS) plication and minimal access cranial suspension (MACS),
      to evaluate the effectiveness of each method in facial excursion. METHODS: Thirty
      six face-lift surgeries were performed on nine cadavers between October and
      December 2010. Both SMAS and MACS surgeries were done on each side of the cadaver
      faces. The average amounts of skin and muscle lifting up and out in three defined
      anatomical landmarks were compared between the two methods, SMAS plication and
      MACS lift procedure. RESULTS: Nine fresh cadavers with the mean age of 53 +/- 6.7
      years entered the study. Seven (77.8 %) were males and two (22.2 %) were females.
      The average amounts of lifting of the anatomical landmarks up and out were
      significantly greater in the SMAS plication method compared to the MACS lift
      procedure (P values <0.05), whereas facial symmetry was not significantly
      different between the two methods. CONCLUSION: The overall amounts of facial skin
      and muscle lifting by the SMAS plication method were greater than the MACS lift
      procedure. However, it does not justify ignoring the benefits of the MACS lift
      procedure in terms of less invasiveness and quicker recovery. NO LEVEL EVIDENCE:
      This journal requires that authors assign a level of evidence to each submission
      to which Evidence-Based Medicine rankings are applicable. 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- 26296637
TI  - Immediate Nipple Reconstruction as Oncoplastic Breast Surgery: the Cigar Roll
      Flap with Inner Dermal Core Technique.
AB  - BACKGROUND: Postoperative loss of projection is the most common problem following
      nipple reconstruction. Despite the various available nipple reconstruction
      techniques, a simple and reliable method that maintains nipple projection has not
      yet been developed. Here, we introduce a simple and feasible method for immediate
      nipple reconstruction-the cigar roll flap with inner dermal core technique-which
      is expected to maintain long-term nipple projection. METHODS: Between January
      2013 and August 2014, 23 breast cancer patients underwent unilateral nipple
      reconstruction using the cigar roll flap with inner dermal core technique during
      immediate breast reconstruction. The projection of the reconstructed nipple was
      measured at the time of surgery and after radiation therapy (average
      postoperative duration, 8 months). RESULTS: The mean nipple projection at the
      time of surgery was 1.1 +/- 0.2 cm. After radiation therapy, the mean projection
      was 1.0 +/- 0.2 cm. The mean maintenance of nipple projection was 84.5 +/- 5.3 %.
      No immediate or delayed major postoperative complications were noted in our
      series. Most of the patients were satisfied with the three-dimensional projection
      of the nipple. CONCLUSIONS: The cigar roll flap with inner dermal core technique
      is a simple and reliable method for oncoplastic breast surgery during immediate
      nipple reconstruction and maintains constant projection without any major
      complications or donor-site morbidity. LEVEL OF EVIDENCE IV: This journal
      requires that authors assign a level of evidence to each article. For a full
      description of these Evidence-Based Medicine ratings, please refer to the Table
      of Contents or the online Instructions to Authors www.springer.com/00266 .

PMID- 26296638
TI  - Changing the Donor Site Selection Concept of Facial Skin Expansion from Pure
      Healthy Tissue to Defect and Healthy Tissue Combination.
AB  - Facial defect reconstruction is a challenge for plastic surgeons due to unique
      esthetic and functional properties of the region. Facial tissue expansion
      provides an ideal reconstruction resource. However, the donor site is limited in
      the facial region. Thus, a cost-effective expansion management is crucial for an
      efficient reconstruction. In this article, the evolution of our donor site
      preference for tissue expansion from pure healthy tissue to a defect-healthy
      tissue combination is presented. Fifteen patients underwent skin reconstruction
      with local tissue expansion for facial and cervical defects. The full facial or
      cervical region including the defect and healthy tissue combination was
      determined as the donor expansion site. The donor site was not limited only to
      pure healthy tissue. The largest size rectangular expander suitable for the
      combined expandable donor site size was placed under the defect and healthy
      tissue border, paying attention to carry the expander far beneath the defect
      site. The defect site and most adjacent healthy tissue were expanded
      simultaneously. Major complications such as infection, hematoma, rupture, or flap
      necrosis were not observed. The expansion of defect-healthy tissue border
      presented successful reconstruction results with acceptable scars. In the
      traditional tissue expansion concept, using a large size expander to provide more
      abundant flap gain does not comply with the limited size of healthy donor site in
      the face. Expanding the whole facial region, without restriction of the defect,
      supplies excess donor tissue area for larger size expander use. Eventually,
      defect-healthy tissue border expansion with large expanders results in minimum
      final scar and less tissue loss in flap relocation and enables optimal flap gain.
      This method can easily be adapted to any tissue expansion site of the body. LEVEL
      OF EVIDENCE IV: This journal requires that authors assign a level of evidence to
      each article. For a full description of these Evidence-Based Medicine ratings,
      please refer to the Table of Contents or the online Instructions to Authors
      www.springer.com/00266 .

PMID- 26296640
TI  - Evaluating Continuous Tumor Measurement-Based Metrics as Phase II Endpoints for
      Predicting Overall Survival.
AB  - BACKGROUND: We sought to develop and validate clinically relevant, early
      assessment continuous tumor measurement-based metrics for predicting overall
      survival (OS) using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
      data warehouse. METHODS: Data from 13 trials representing 2096 patients with
      breast cancer, non-small cell lung cancer (NSCLC), or colorectal cancer were used
      in a complete case analysis. Tumor measurements from weeks 0-6-12 assessments
      were used to evaluate the ability of slope (absolute change in tumor size from 0
      6 and 6-12 weeks) and percent change (relative change in tumor size from 0-6 and
      6-12 weeks) metrics to predict OS using Cox models, adjusted for average baseline
      tumor size. Metrics were evaluated by discrimination (via concordance or c
      index), calibration (goodness-of-fit type statistics), association (hazard
      ratios), and likelihood (Bayesian Information Criteria), with primary focus on
      the c-index. All statistical tests were two-sided. RESULTS: Comparison of c
      indices suggests slight improvement in predictive ability for the continuous
      tumor measurement-based metrics vs categorical RECIST response metrics, with
      slope metrics performing better than percent change metrics for breast cancer and
      NSCLC. However, these differences were not statistically significant. The
      goodness-of-fit statistics for the RECIST metrics were as good as or better than
      those for the continuous metrics. In general, all the metrics performed poorly in
      breast cancer, compared with NSCLC and colorectal cancer. CONCLUSION: Absolute
      and relative change in tumor measurements do not demonstrate convincingly
      improved overall survival predictive ability over the RECIST model. Continued
      work is necessary to address issues of missing tumor measurements and model
      selection in identifying improved tumor measurement-based metrics.

PMID- 26296639
TI  - Recent advances in nanotechnology-based detection and separation of circulating
      tumor cells.
AB  - Although circulating tumor cells (CTCs) in blood have been widely investigated as
      a potential biomarker for diagnosis and prognosis of metastatic cancer, their
      inherent rarity and heterogeneity bring tremendous challenges to develop a CTC
      detection method with clinically significant specificity and sensitivity. With
      advances in nanotechnology, a series of new methods that are highly promising
      have emerged to enable or enhance detection and separation of CTCs from blood. In
      this review, we systematically categorize nanomaterials, such as gold
      nanoparticles, magnetic nanoparticles, quantum dots, graphenes/graphene oxides,
      and dendrimers and stimuli-responsive polymers, used in the newly developed CTC
      detection methods. This will provide a comprehensive overview of recent advances
      in the CTC detection achieved through application of nanotechnology as well as
      the challenges that these existing technologies must overcome to be directly
      impactful on human health.

PMID- 26296641
TI  - Predicting Response to Histone Deacetylase Inhibitors Using High-Throughput
      Genomics.
AB  - BACKGROUND: Many disparate biomarkers have been proposed as predictors of
      response to histone deacetylase inhibitors (HDI); however, all have failed when
      applied clinically. Rather than this being entirely an issue of reproducibility,
      response to the HDI vorinostat may be determined by the additive effect of
      multiple molecular factors, many of which have previously been demonstrated.
      METHODS: We conducted a large-scale gene expression analysis using the Cancer
      Genome Project for discovery and generated another large independent cancer cell
      line dataset across different cancers for validation. We compared different
      approaches in terms of how accurately vorinostat response can be predicted on an
      independent out-of-batch set of samples and applied the polygenic marker
      prediction principles in a clinical trial. RESULTS: Using machine learning, the
      small effects that aggregate, resulting in sensitivity or resistance, can be
      recovered from gene expression data in a large panel of cancer cell lines.This
      approach can predict vorinostat response accurately, whereas single gene or
      pathway markers cannot. Our analyses recapitulated and contextualized many
      previous findings and suggest an important role for processes such as chromatin
      remodeling, autophagy, and apoptosis. As a proof of concept, we also discovered a
      novel causative role for CHD4, a helicase involved in the histone deacetylase
      complex that is associated with poor clinical outcome. As a clinical validation,
      we demonstrated that a common dose-limiting toxicity of vorinostat,
      thrombocytopenia, can be predicted (r = 0.55, P = .004) several days before it is
      detected clinically. CONCLUSION: Our work suggests a paradigm shift from single
      gene/pathway evaluation to simultaneously evaluating multiple independent high
      throughput gene expression datasets, which can be easily extended to other
      investigational compounds where similar issues are hampering clinical adoption.

PMID- 26296643
TI  - Gender Disparity and Mutation Burden in Metastatic Melanoma.
AB  - Gender differences in melanoma incidence and outcome have been consistently
      observed but remain biologically unexplained. We hypothesized that tumors are
      genetically distinct between men and women and analyzed the mutation spectra in
      266 metastatic melanomas (102 women and 164 men) from The Cancer Genome Atlas
      (TCGA). We found a statistically significantly greater burden of missense
      mutations among men (male median 298 vs female median = 211.5; male-to-female
      ratio [M:F] = 1.85, 95% confidence interval [CI] = 1.44 to 2.39). We validated
      these initial findings using available data from a separate melanoma exome cohort
      (n = 95) and found a similar increase in missense mutations among men (male
      median 393 vs female median 259; M:F = 1.59, 95% CI = 1.12 to 2.27). In addition,
      we found improved survival with increasing log-transformed missense mutation
      count (univariate hazard ratio = 0.82, 95% CI = 0.69 to 0.98) for TCGA samples.
      Our analyses demonstrate for the first time a gender difference in mutation
      burden in cutaneous melanoma. 

PMID- 26296644
TI  - Characterizing the insecticide resistance of Anopheles gambiae in Mali.
AB  - BACKGROUND: The impact of indoor residual spraying (IRS) and long-lasting
      insecticide nets (LLINs), key components of the national malaria control strategy
      of Mali, is threatened by vector insecticide resistance. The objective of this
      study was to assess the level of insecticide resistance in Anopheles gambiae
      sensu lato populations from Mali against four classes of insecticide recommended
      for IRS: organochlorines (OCs), pyrethroids (PYs), carbamates (CAs) and
      organophosphates (OPs). Characterization of resistance was done in 13 sites
      across southern Mali and assessed presence and distribution of physiological
      mechanisms that included target-site modifications: knockdown resistance (kdr)
      and altered acetycholinesterase (AChE), and/or metabolic mechanisms: elevated
      esterases, glutathione S-transferases (GSTs), and monooxygenases. METHODS: The
      World Health Organization (WHO) tube test was used to determine phenotypic
      resistance of An. gambiae s.l. to: dichlorodiphenyltrichloroethane (DDT) (OC),
      deltamethrin (PY), lambda-cyhalothrin (PY), bendiocarb (CA), and fenitrothion
      (OP). Identification of sibling species and presence of the ace-1 (R) and Leu-Phe
      kdr, resistance-associated mutations, were determined using polymerase chain
      reaction (PCR) technology. Biochemical assays were conducted to detect increased
      activity of GSTs, oxidases and esterases. RESULTS: Populations tested showed high
      levels of resistance to DDT in all 13 sites, as well as increased resistance to
      deltamethrin and lambda-cyhalothrin in 12 out of 13 sites. Resistance to
      fenitrothion and bendiocarb was detected in 1 and 4 out of 13 sites,
      respectively. Anopheles coluzzii, An. gambiae sensu stricto and Anopheles
      arabiensis were identified with high allelic frequencies of kdr in all sites
      where each of the species were found (13, 12 and 10 sites, respectively).
      Relatively low allelic frequencies of ace-1 (R) were detected in four sites where
      this assessment was conducted. Evidence of elevated insecticide metabolism, based
      on oxidase, GSTs and esterase detoxification, was also documented. CONCLUSION:
      Multiple insecticide-resistance mechanisms have evolved in An. coluzzii, An.
      gambiae s.s. and An. arabiensis in Mali. These include at least two target site
      modifications: kdr, and ace-1 (R) , as well as elevated metabolic detoxification
      systems (monooxygenases and esterases). The selection pressure for resistance
      could have risen from the use of these insecticides in agriculture, as well as in
      public health. Resistance management strategies, based on routine resistance
      monitoring to inform insecticide-based malaria vector control in Mali, are
      recommended.

PMID- 26296645
TI  - let-7b suppresses apoptosis and autophagy of human mesenchymal stem cells
      transplanted into ischemia/reperfusion injured heart 7by targeting caspase-3.
AB  - INTRODUCTION: Mesenchymal stem cells (MSCs) have therapeutic potential for the
      repair of myocardial injury. The efficacy of MSC therapy for myocardial
      regeneration mainly depends on the survival of cells after transplantation into
      the infarcted heart. In the transplanted regions, reactive oxygen species (ROS)
      can cause cell death, and this process depends on caspase activation and
      autophagosome formation. METHODS: A Software TargetScan was utilized to search
      for microRNAs (miRNAs) that target caspase-3 mRNA. Six candidate miRNAs including
      let-7b were selected and transfected into human MSCs in vitro. Expression of MEK
      EKR signal pathways and autophagy-related genes were detected. Using
      ischemia/reperfusion model (I/R), the effect of MSCs enriched with let-7b was
      determined after transplantation into infarcted heart area. Miller catheter was
      used to evaluate cardiac function. RESULTS: Here, we report that let-7b targets
      caspase-3 to regulate apoptosis and autophagy in MSCs exposed to ROS. Let-7b
      transfected MSCs (let-7b-MSCs) showed high expression of survival-related
      proteins, including p-MEK, p-ERK and Bcl-2, leading to a decrease in Annexin V/PI
      and TUNEL-positive cells under ROS-rich conditions. Moreover, autophagy-related
      genes, including Atg5, Atg7, Atg12 and beclin-1, were significantly downregulated
      in let-7b-MSCs. Using a rat model of acute myocardial infarction, we found that
      intramyocardial injection of let-7b-MSCs markedly enhanced left ventricular (LV)
      function and microvessel density, in accordance with a reduced infarct size and
      the expression of caspase-3. CONCLUSIONS: Taken together, these data indicate
      that let-7b may protect MSCs implanted into infarcted myocardium from apoptosis
      and autophagy by directly targeting caspase-3 signaling.

PMID- 26296646
TI  - XXXV Congress of the SEMNIM. Highlights.

PMID- 26296647
TI  - Influence of antenatal physical exercise on haemodynamics in pregnant women: a
      flexible randomisation approach.
AB  - BACKGROUND: Normal pregnancy is associated with marked changes in haemodynamic
      function, however the influence and potential benefits of antenatal physical
      exercise at different stages of pregnancy and postpartum remain unclear. The aim
      of this study was therefore to characterise the influence of regular physical
      exercise on haemodynamic variables at different stages of pregnancy and also in
      the postpartum period. METHODS: Fifty healthy pregnant women were recruited and
      randomly assigned (2 * 2 * 2 design) to a land or water-based exercise group or a
      control group. Exercising groups attended weekly classes from the 20th week of
      pregnancy onwards. Haemodynamic assessments (heart rate, cardiac output, stroke
      volume, total peripheral resistance, systolic and diastolic blood pressure and
      end diastolic index) were performed using the Task Force haemodynamic monitor at
      12-16, 26-28, 34-36 and 12 weeks following birth, during a protocol including
      postural manoeurvres (supine and standing) and light exercise. RESULTS: In
      response to an acute bout of exercise in the postpartum period, stroke volume and
      end diastolic index were greater in the exercise group than the non-exercising
      control group (p = 0.041 and p = 0.028 respectively). Total peripheral resistance
      and diastolic blood pressure were also lower (p = 0.015 and p = 0.007,
      respectively) in the exercise group. Diastolic blood pressure was lower in the
      exercise group during the second trimester (p = 0.030). CONCLUSIONS: Antenatal
      exercise does not appear to substantially alter maternal physiology with
      advancing gestation, speculating that the already vast changes in maternal
      physiology mask the influences of antenatal exercise, however it does appear to
      result in an improvement in a woman's haemodynamic function (enhanced ventricular
      ejection performance and reduced blood pressure) following the end of pregnancy.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT02503995. Registered 20 July 2015.

PMID- 26296648
TI  - Flow cytometry screening for paroxysmal nocturnal hemoglobinuria: A single-center
      experience in Saudi Arabia.
AB  - BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal
      hematopoietic stem cell disorder, characterized by the deficiency of
      glycosylphosphatidylinositol (GPI) that anchors proteins in cell membranes. PNH
      is manifest variously with hemoglobinuria, thrombosis, or bone marrow failure.
      This retrospective study was aimed at assessing the incidence and characteristics
      of patients diagnosed with PNH in the King Fisal Specialist Hospital and research
      center. METHODS: Patients referred for PNH diagnosis at King Faisal Specialist
      Hospital and Research Centre, Riyadh, during the 2-year period (2012-2013) were
      included in the analysis. Peripheral blood samples were used for multi-parametric
      flow cytometry analysis based on fluorescent inactive aerolysin (FLAER), and the
      markers, CD235a and CD59 on red blood cells (RBCs), and CD14, CD45, CD64, CD24,
      and CD15 on white blood cells (WBCs) exclusively monocytes and granulocytes.
      Univariate analysis of the disease characteristics was performed. RESULTS: Of the
      366 samples submitted for PNH screening, 14 were positive (4%) and 11 were
      evaluable. Of the 11 patients analyzed, 8 patients (73%) presented with aplastic
      anemia, 1 patient (9%) each with pancytopenia, Budd-Chiari syndrome, and immune
      thrombocytopenia purpura. All samples showed type II and III GPI-deficient clones
      with a median clone size of 15% (range, 0.7%-56%) in the RBCs, and 63% (range,
      3.8%-100%) in WBCs (monocytes and granulocytes). CONCLUSIONS: This study confirms
      the rarity of PNH and its predominant presentation as aplastic anemia or
      thrombosis in a Saudi Arabian population, similar to the worldwide incidence.

PMID- 26296649
TI  - Auditory Neuropathy/Dys-Synchrony Disorder: Diagnosis and Management.
AB  - Auditory neuropathy/dys-synchrony disorder affects neural responses, either
      directly or indirectly. Patients may demonstrate good ability to detect sound,
      but have significant difficulty listening in noise. Clinical auditory physiologic
      measures are used to characterize cochlear, eighth nerve, and brainstem function,
      and are needed to accurately identify this disorder. Cochlear implants provide
      benefit to many patients, and some patients derive benefit from amplification.
      This disorder can be identified and managed in infants, may have later onset, may
      be a part of a syndrome, and may include fluctuation in hearing ability. 

PMID- 26296650
TI  - Carcinoma showing thymus-like differentiation (CASTLE): Report of a case
      specified in the cytomorphology.

PMID- 26296642
TI  - Height and Breast Cancer Risk: Evidence From Prospective Studies and Mendelian
      Randomization.
AB  - BACKGROUND: Epidemiological studies have linked adult height with breast cancer
      risk in women. However, the magnitude of the association, particularly by
      subtypes of breast cancer, has not been established. Furthermore, the mechanisms
      of the association remain unclear. METHODS: We performed a meta-analysis to
      investigate associations between height and breast cancer risk using data from
      159 prospective cohorts totaling 5216302 women, including 113178 events. In a
      consortium with individual-level data from 46325 case patients and 42482 control
      patients, we conducted a Mendelian randomization analysis using a genetic score
      that comprised 168 height-associated variants as an instrument. This association
      was further evaluated in a second consortium using summary statistics data from
      16003 case patients and 41335 control patients. RESULTS: The pooled relative risk
      of breast cancer was 1.17 (95% confidence interval [CI] = 1.15 to 1.19) per 10cm
      increase in height in the meta-analysis of prospective studies. In Mendelian
      randomization analysis, the odds ratio of breast cancer per 10cm increase in
      genetically predicted height was 1.22 (95% CI = 1.13 to 1.32) in the first
      consortium and 1.21 (95% CI = 1.05 to 1.39) in the second consortium. The
      association was found in both premenopausal and postmenopausal women but
      restricted to hormone receptor-positive breast cancer. Analyses of height
      associated variants identified eight new loci associated with breast cancer risk
      after adjusting for multiple comparisons, including three loci at 1q21.2,
      DNAJC27, and CCDC91 at genome-wide significance level P < 5*10(-8). CONCLUSIONS:
      Our study provides strong evidence that adult height is a risk factor for breast
      cancer in women and certain genetic factors and biological pathways affecting
      adult height have an important role in the etiology of breast cancer.

PMID- 26296651
TI  - A Clustered Randomized Controlled Trial to Reduce Secondhand Smoke Exposure Among
      Nonsmoking Pregnant Women in Sichuan Province, China.
AB  - INTRODUCTION: Nonsmoking pregnant women in China have significant exposure to
      secondhand smoke (SHS). Few interventions have focused on pregnant women reducing
      their SHS exposure. METHODS: This clustered randomized controlled trial,
      conducted at eight hospitals in Sichuan, China, compared a prenatal health
      education intervention with usual clinical care as a control. The primary outcome
      was self-reported "no SHS exposure" before and 3 months after birth. The
      intervention consisted of three large group educational sessions, standardized
      clinician advice, brief monthly follow-up calls, and educational materials and
      resources. A random sample of participants was biochemically validated before
      birth with hair nicotine, a long-term biomarker of smoke exposure. RESULTS:
      Overall, 1181 participants were randomized to intervention (n = 526) and control
      (n = 655) groups. More participants in the intervention group than the control
      group reported no SHS exposure 3 months after birth (Total: 77.9% vs. 52.6%, P <
      .001; Home: 81.2% vs. 53.3%, P < .001). The intervention group also had greater
      changes in improved smoke-free homes and SHS knowledge and attitudes. Controlling
      for covariates, the intervention group was less likely to report SHS exposure
      than the control group (Total: OR = 0.47, 95% CI = 0.31 to 0.71; Home: OR = 0.33,
      95% CI = 0.21 to 0.53), and this effect was sustained 3 months after birth. The
      adjusted log concentration of hair nicotine for the intervention group decreased
      by 0.28 log ug/g more than the control group. CONCLUSIONS: Our smoke-free health
      education intervention for nonsmoking pregnant women significantly reduced SHS
      exposure before and after birth. This intervention model can become part of a
      standard protocol for the care of pregnant women in hospital settings.

PMID- 26296653
TI  - The experiences of self-care in community-dwelling older people: a meta
      synthesis.
AB  - OBJECTIVES: To identify, critically appraise and synthesize qualitative evidence
      of self-care experiences in health promotion for home-dwelling elders. DESIGN: A
      meta-synthesis was conducted following the Joanna Briggs Institute guidelines and
      using Qualitative Assessment and Review Instrument Software. DATA SOURCES: The
      literature search was conducted on PubMed, CINHAL, Embase, PsycInfo, Eric and
      ILISI databases from inception up until March 2015. Other articles were searched
      on Scopus and Web of Knowledge. The reference list of all the identified articles
      was also searched for additional studies. Studies published in English, Italian,
      French, Portuguese, and Spanish were considered for inclusion in the review.
      REVIEW METHODS: Data from the selected qualitative articles were extracted
      independently by two reviewers using the data extraction tool of the Joanna
      Briggs Institute-Qualitative Assessment and Review Instrument. The meta-synthesis
      involved the following three steps: the production of a set of statements
      representing the aggregated data obtained by assembling the findings of
      qualitative studies; the categorization of findings on the basis of similarity in
      meaning; and the aggregation of these categories to produce a comprehensive set
      of synthesized findings. No studies were excluded due to methodological quality.
      RESULTS: Of the 4001 records identified, 11 articles met the inclusion criteria.
      Most articles were conducted in Scandinavian countries and used a
      phenomenological design. Most elders in the sample were middle-class, cognitively
      intact, independent, and in good health. The meta-synthesis revealed that older
      people living at home make decisions about their self-care activities on the
      basis of their attitudes toward their life and future. These self-care activities
      are directed toward holistic wellness, prevention and treatment of aging effects,
      obtaining a sense of satisfaction, and self-realization. Furthermore, self-care
      activities are settled in a social and relational network that allows old people
      to take care of themselves and of others or to be cared for by others.
      CONCLUSIONS: This meta-synthesis presents the perspectives of home-dwelling old
      people on health-promoting self-care experiences. Such information can help
      healthcare professionals to maintain long-term autonomy of elders in self-care
      and to promote healthy aging. Further qualitative research describing self-care
      experiences of home-dwelling elders from different cultures, education levels,
      and social backgrounds is needed.

PMID- 26296652
TI  - Bilateral diaphyseal bone cysts of the tibia mimicking shin splints in a young
      professional athlete--a case report and depiction of a less-invasive surgical
      technique.
AB  - BACKGROUND: Medial tibial stress syndrome is one of the most common causes of
      exertional leg pain in runners whereas musculoskeletal tumors and tumor-like
      lesions are rare encounters in orthopedic sports medicine practice. Unicameral
      (simple) bone cyst is a well-known tumor-like lesions of the bone typically
      affecting children and adolescents. Bilateral occurrence is very rare though and
      has never been reported before in both tibiae. Failing to accurately diagnose a
      tumorous lesion can entail far-reaching consequences for both patients and
      physicians. CASE PRESENTATION: We report the case of large bilateral unicameral
      bone cysts of the diaphyseal tibiae mimicking medial tibial stress syndrome in a
      17-year old professional athlete. This is the first report of symmetric tibial
      unicameral bone cysts in the literature. The patient complained about persisting
      shin splint-like symptoms over 5 months despite comprehensive conservative
      treatment before MRI revealed extensive osteolytic bone lesions in both
      diaphyseal tibiae. The patient-tailored, less-invasive surgical procedure,
      allowing the patient to return to his competitive sports level symptom-free 3
      months after surgery and to eventually qualify for this years Biathlon Junior
      World Championships, is outlined briefly. Pathogenesis and various treatment
      options for this entity will be discussed. CONCLUSION: This report will help to
      raise awareness for musculoskeletal tumors as differential diagnosis for therapy
      refractory symptoms in young athletes and encourage medical staff involved in
      sports medicine and athlete support to perform early high quality imaging and
      initiate sufficient surgical treatment in similar cases. Moreover, our less
      invasive surgical procedure aiming for a fast return to sports might be an
      optimal compromise between traditional open curettage with low risk of recurrence
      and a soft tissue-saving and bone-sparing minimal-invasive technique.

PMID- 26296654
TI  - Older residents' perspectives on aged sexuality in institutionalized elderly
      care: a systematic literature review.
AB  - OBJECTIVES: The aim of this systematic literature review is to investigate older
      residents' thoughts on, experiences of and engagement in sexual behavior and aged
      sexuality within institutionalized elderly care. DESIGN: Systematic literature
      review. DATA SOURCES: We conducted an extensive search of the electronic
      databases Cinahl, Medline, Pubmed, Embase, Web of Science and Invert for papers
      published between January 1980 and October 2014 when the searches were closed.
      Additional papers were identified through forward and backward citation chasing.
      REVIEW METHODS: Data from relevant studies were extracted by means of a data
      extraction form. Relevant data were isolated, summarized, compared, related and
      categorized according to theme. Quality assessment of the included studies
      focused on their adequacy of reporting the study's research aim, sampling,
      collection, and analysis procedures, ethical considerations and results. RESULTS:
      Twenty-five appropriate studies were identified. These studies varied in research
      design (using surveys, vignettes, focus groups, interviews, or observation),
      objectives, quality of reporting, and sample characteristics (i.e. male and/or
      female long-term care residents with and/or without dementia). Yet, they all
      point to the relevance of sex and sexuality in old age and emphasize the highly
      individual character of both sexual interest and expression. Older residents who
      wish to sexually express themselves, might do this in a wide variety of ways,
      including, but not limited to, daydreaming, dressing-up, looking for emotional
      and intellectual intimacy, stroking, caressing, kissing, and engaging in sexual
      intercourse. Overall, residents appear to have a rather positive attitude toward
      aged sexuality as such. When it comes to specific sexual behaviors or
      homosexuality, however, attitudes tend to be more negative. The perceived
      appropriateness of the displayed behavior is a predominant factor in determining
      older people's reactions to the sexual behavior of co-residents, rather than the
      potential emotional discomfort brought on by witnessing this behavior.
      CONCLUSIONS: Relatively little work has been published on older residents'
      perspectives regarding aged sexuality in institutionalized elderly care. If,
      however, we wish to devote ourselves to individualized or person-centered nursing
      care, we will have to gain more insight into the patient's perspective and take
      notice of the needs, expectations, attitudes, experiences and behaviors of
      residents with regard to (aged) sexuality. Hence more research is needed that
      depicts the issue of aged sexuality in institutionalized elderly care from a
      patient's and thus resident oriented perspective.

PMID- 26296656
TI  - hHR23A is required to control the basal turnover of Chk1.
AB  - Among other functions, the Chk1 protein plays an essential role in coordinating
      the cellular stress response by determining cell cycle arrest. The levels of Chk1
      expression and activity are critical for its functions, especially in cell cycle
      progression, genomic integrity, cell viability and tissue development. Chk1
      protein expression should therefore be tightly controlled both during normal
      growth and under stress situations. However, it is still unknown how Chk1 protein
      levels are regulated during normal cell cycle progression. In this study, we show
      that the effect of hHR23A on Chk1 protein turnover could impact the cell cycle
      progression observed in hHR23A-knockdown cells. Our results reveal that hHR23A
      associates with Chk1 through its UBA domains, and that knockdown of hHR23A
      increases and stabilizes the protein level of Chk1 and its phosphorylation at
      S347. Knockdown of hHR23A results in proliferation defects and S-phase
      accumulation. DNA damage reduces the interaction between Chk1 and hHR23A,
      releasing Chk1 from hHR23A and enhancing S-phase accumulation. Based on these
      novel findings, we propose that hHR23A acts as a carrier to promote Chk1
      degradation through the Ubiquitin Proteasome System. These results strengthen the
      model in which DNA damage induces Chk1 phosphorylation on chromatin followed by
      releasing phospho-Chk1 from the chromatin into soluble nucleus and the cytoplasm
      where Chk1 activates the cell cycle checkpoints; and finally, Chk1 is degraded
      and checkpoint signaling is terminated. 

PMID- 26296655
TI  - Candidate effectors contribute to race differentiation and virulence of the
      lentil anthracnose pathogen Colletotrichum lentis.
AB  - BACKGROUND: The hemibiotroph Colletotrichum lentis, causative agent of
      anthracnose on Lens culinaris (lentil) was recently described as a new species.
      During its interaction with the host plant, C. lentis likely secretes numerous
      effector proteins, including toxins to alter the plant's innate immunity, thereby
      gaining access to the host tissues for nutrition and reproduction. RESULTS: In
      silico analysis of 2000 ESTs generated from C. lentis-infected lentil leaf
      tissues identified 15 candidate effectors. In planta infection stage-specific
      gene expression waves among candidate effectors were revealed for the
      appressorial penetration phase, biotrophic phase and necrotrophic phase. No sign
      of positive selection pressure [omega (dN/dS) < 1] in effectors was detected at
      the intraspecific level. A single nucleotide polymorphism in the ORF of candidate
      effector ClCE6, used to develop a KASPar marker, differentiated perfectly between
      pathogenic race 0 and race 1 isolates when tested on 52 isolates arbitrarily
      selected from a large culture collection representing the western Canadian
      population of C. lentis. Furthermore, an EST encoding argininosuccinate lyase
      (Arg) was identified as a bacterial gene. A toxin protein ClToxB was further
      characterized as a potential host-specific toxin through heterologous in planta
      expression. The knock-down of ClToxB transcripts by RNAi resulted in reduced
      virulence, suggesting that ClToxB is a virulence factor. In silico analysis of
      the ClToxB sequence and comparative genomics revealed that ToxB is unlikely a
      foreign gene in the C. lentis genome. Incongruency between established species
      relationships and that established based on gene sequence data confirmed ToxB
      arose through evolution from a common ancestor, whereas the bacterial gene Arg
      identified in C. lentis was horizontally transferred from bacteria. CONCLUSIONS:
      EST mining and expression profiling revealed a set of in planta expressed
      candidate effectors. We developed a KASPar assay using effector polymorphism to
      differentiate C. lentis races. Comparative genomics revealed a foreign gene
      encoding a potential virulence factor Arg, which was horizontally transferred
      from bacteria into the genus Colletotrichum. ClToxB is further characterized as a
      host-specific toxin that is likely to contribute to quantitative differences in
      virulence between the races 0 and 1.

PMID- 26296657
TI  - pVHL interacts with Ceramide kinase like (CERKL) protein and ubiquitinates it for
      oxygen dependent proteasomal degradation.
AB  - Mutations of Ceramide kinase-like (CERKL) gene are associated with retinitis
      pigmentosa (RP), an inherited degenerative eye disease. CERKL encodes an
      antioxidant protein which is critical to photoreceptor survival, its deficiency
      causes retinal degeneration as a result of oxidative damage. However, the
      regulation of CERKL in response to oxidative stress, and its contribution to
      photoreceptor survival remain unclear. pVHL, the substrate receptor of RING
      finger-type SCF like ECV ubiquitin ligase, binds and ubiquitinates a number of
      hydroxylated proteins for proteasomal degradation. Due to hydroxylated proteins
      which are modified by PHD1-3, pVHL dependent ubiquitin-proteasomal degradation
      pathway is blocked by PHD1-3 inhibitors (e.g. hypoxia or oxidative stress). In
      this study, we identified pVHL as an important regulator of CERKL. Western blot
      and in vivo ubiquitination assays showed hypoxia up-regulates CERKL at protein
      level by down-regulating its poly-ubiquitination. By Co-IP and domain mapping
      studies, we found CERKL complexes with ECV ligase via pVHL. Through
      overexpression and small RNA interference analysis, we demonstrated pVHL
      ubiquitinates CERKL for proteasomal degradation. Additionally, our work showed
      that the oxygen sensors PHD1 and PHD3 are involved in CERKL degradation.
      Collectively, our results indicated that pVHL interacts with CERKL and
      ubiquitinates it for oxygen dependent proteasomal degradation. 

PMID- 26296658
TI  - Dimer of arfaptin 2 regulates NF-kappaB signaling by interacting with
      IKKbeta/NEMO and inhibiting IKKbeta kinase activity.
AB  - IkappaB kinases (IKKs) are a therapeutic target due to their crucial roles in
      various biological processes, including the immune response, the stress response,
      and tumor development. IKKs integrate various upstream signals that activate NF
      kappaB by phosphorylating IkappaB and also regulate many proteins related to cell
      growth and metabolism. Although they function as a heteromeric complex comprised
      of kinase subunits and an adaptor, these kinases produce distinct cellular
      responses by phosphorylating different target molecules, suggesting that they may
      also be regulated in a subtype-specific manner. In this study, arfaptin 2 was
      identified as an IKKbeta-specific binding partner. Interestingly, arfaptin 2 also
      interacted with NEMO. Domain mapping studies revealed that the C-terminal region,
      including the IKKbeta HLH domain and the first coiled-coil NEMO region were
      respectively required for interactions with the arfaptin 2 N-terminal flexible
      region. Overexpression of arfaptin 2 inhibited tumor necrosis factor (TNF)-alpha
      stimulated nuclear factor-kappaB (NF-kappaB) signaling, whereas downregulation of
      arfaptin 2 by small interfering RNA enhanced NF-kappaB activity. Dimerization of
      arfaptin 2 through the Bin-Amphiphysin-Rvs domain may be essential to inhibit
      activation of NF-kappaB through multimodal interactions with IKKbetas or
      IKKbeta/NEMO, as ectopic expression of the arfaptin 2 fragment responsible for
      IKK interactions did not change TNFalpha-stimulated NF-kappaB activation. These
      data indicate that arfaptin 2 is the first molecule to regulate NF-kappaB
      signaling by interacting with the functional IKK complex but not by direct
      inhibiting IKKbeta phosphorylation. 

PMID- 26296659
TI  - Does ultrasound provide any added value in breast contouring for radiotherapy
      after conserving surgery for cancer?
AB  - BACKGROUND: Whole breast irradiation after conserving surgery for breast cancer
      requires precise definition of the target volume. The standard approach uses
      computed tomography (CT) images. However, since fatty breast and non-breast
      tissues have similar electronic densities, difficulties in differentiating
      between them hamper breast volume delineation. To overcome this limitation the
      breast contour is defined by palpation and then radio-opaque wire is put around
      it before the CT scan. To optimize assessment of breast margins in the cranial,
      caudal, medial, lateral and posterior directions, the present study evaluated
      palpation and CT and determined whether ultrasound (US) provided any added value.
      METHODS: Twenty consecutive patients were enrolled after they had provided
      informed consent to participating in this prospective study which was approved by
      the Regional Public Health Ethics Committee. Palpation and US defined breast
      margins and each contour was marked and outlined with a fine plastic wire.
      Breasts were then contoured on axial CT images using the breast window width (WW)
      and window level (WL) (401 and 750 Hounsfield Units -HU- respectively), at which
      setting the plastic wires were invisible. Then, the lung window function (WW 1601
      HU; WL -300 HU) was inserted to visualize the plastic wires which were used as
      guidelines to contour the palpable and US breast volumes. As each wire had a
      different diameter, both volumes were easily defined on CT slices. Results were
      analyzed using descriptive statistics, percentage overlap and reproducibility
      measures (agreement and reliability). RESULTS: Volumes: US gave the largest and
      palpation the smallest. Agreement was best between palpation and CT. Reliability
      was almost perfect in all correlations. Extensions: Cranial and posterior were
      highest with US and smallest with palpation. Agreement was best between palpation
      and CT in all extensions except the cranial. Since strong to almost perfect
      agreement emerged for all comparisons, reliability was high. CONCLUSIONS: US may
      be useful in defining the cranial and posterior extensions, mainly when tumours
      are localized there. This study demonstrates that the now standard radio-opaque
      wires around the palpable breast may not be needed in breast contouring.

PMID- 26296660
TI  - New assay for Gardnerella vaginalis loads correlates with Nugent scores and has
      potential in the diagnosis of bacterial vaginosis.
AB  - Gardnerella vaginalis is a Gram-variable anaerobic bacterium present in 100% of
      women with bacterial vaginosis (BV). BV is a complex polymicrobial condition with
      no single causative agent. The current laboratory detection method for BV relies
      on a Gram-stain Nugent score to estimate the quantity of different bacterial
      morphotypes in the vaginal micro flora. Whilst the Nugent score can distinguish
      between women with and without BV, a significant proportion are categorized as
      intermediate, which fails to differentiate a normal from an abnormal vaginal
      micro flora. A singleplex G. vaginalis TaqMan real-time quantitative PCR (qPCR)
      assay was developed and compared with the 'gold standard' Nugent score. Detection
      and quantification of G. vaginalis was performed on vaginal specimens with
      positive, negative and intermediate Nugent scores. The G. vaginalis qPCR assay
      demonstrated high analytical specificity against a broad microbial panel and
      analytical sensitivity down to 3.1 * 10(4) copies ml(-1). There was a
      significantly higher G. vaginalis load in women with BV compared with
      intermediate and non-BV women (P value = 5.1 * 10(-14)). All Nugent scores in
      keeping with BV had qPCR loads of >= 10(7) copies ml(-1). Among the 24 undefined
      women (11.8%) in the study with an intermediate flora, 14 (58.3%) had a G.
      vaginalis load of >= 10(7) copies ml(-1). In this study a threshold of 107 copies
      ml(-1) had positive and negative predictive values of 57.1 and 100% for BV; the
      high qPCR loads among the intermediate Nugent scores suggest the need for a new
      approach in classifying BV and the potential for qPCR to play a role.

PMID- 26296661
TI  - Effect of acute stretch injury on action potential and network activity of rat
      neocortical neurons in culture.
AB  - The basis for acute seizures following traumatic brain injury (TBI) remains
      unclear. Animal models of TBI have revealed acute hyperexcitablility in cortical
      neurons that could underlie seizure activity, but studying initiating events
      causing hyperexcitability is difficult in these models. In vitro models of
      stretch injury with cultured cortical neurons, a surrogate for TBI, allow facile
      investigation of cellular changes after injury but they have only demonstrated
      post-injury hypoexcitability. The goal of this study was to determine if neuronal
      hyperexcitability could be triggered by in vitro stretch injury. Controlled
      uniaxial stretch injury was delivered to a spatially delimited region of a
      spontaneously active network of cultured rat cortical neurons, yielding a region
      of stretch-injured neurons and adjacent regions of non-stretched neurons that did
      not directly experience stretch injury. Spontaneous electrical activity was
      measured in non-stretched and stretch-injured neurons, and in control neuronal
      networks not subjected to stretch injury. Non-stretched neurons in stretch
      injured cultures displayed a three-fold increase in action potential firing rate
      and bursting activity 30-60 min post-injury. Stretch-injured neurons, however,
      displayed dramatically lower rates of action potential firing and bursting. These
      results demonstrate that acute hyperexcitability can be observed in non-stretched
      neurons located in regions adjacent to the site of stretch injury, consistent
      with reports that seizure activity can arise from regions surrounding the site of
      localized brain injury. Thus, this in vitro procedure for localized neuronal
      stretch injury may provide a model to study the earliest cellular changes in
      neuronal function associated with acute post-traumatic seizures.

PMID- 26296662
TI  - Tamilnaduibacter salinus gen. nov., sp. nov., a halotolerant gammaproteobacterium
      within the family Alteromonadaceae, isolated from a salt pan in Tamilnadu, India.
AB  - Two novel Gram-stain-negative, slow-growing, halotolerant strains with rod-shaped
      cells, designated as strains Mi-7T and Mi-8, which formed pin-point colonies on
      halophilic media were isolated during a study into the microbial diversity of a
      salt pan in the state of Tamilnadu, India. Both the strains had an obligate
      requirement for 1 % (w/v) NaCl for growth and were halotolerant, growing at NaCl
      concentrations of up to 20 % (w/v) in media. The strains, however, showed an
      inability to utilize the majority of substrates tested as sole carbon sources for
      growth and in fermentation reactions. Molecular phylogenetic analyses, based on
      16S rRNA gene sequence revealed their closest phylogenetic neighbours to be
      members of the genus Marinobacter, with whom they showed the highest sequence
      similarity of 93.6 % and even less with the type strain of the type species,
      Marinobacter hydrocarbonoclasticus DSM 8798T (91.1 %). Similarities with other
      genera within the family Alteromonadaceae were below 91.0 %. However, the two
      strains were very closely related to each other with 99.9 % sequence similarity,
      and DNA-DNA hybridization analyses confirmed their placement in the same species.
      The DNA G+C content of both strains was 65 mol%. Using the polyphasic taxonomic
      data obtained from this study, strains Mi-7T and Mi-8 represent two strains of
      the same species of a novel genus for which the name Tamilnaduibacter salinus
      gen. nov., sp. nov., is proposed; the type strain of the novel species is Mi-7T (
      = MTCC 12009T = DSM 28688T).

PMID- 26296663
TI  - Pedobacter lignilitoris sp. nov., isolated from wood falls.
AB  - A Gram-stain-negative, aerobic, non-motile and rod-shaped bacterial strain,
      designated W-WS13T, was isolated from wood falls collected around Wando, an
      island in the South Sea of South Korea, and subjected to a polyphasic taxonomic
      study. Strain W-WS13T grew optimally at 30  degrees C, at pH 7.5 and in the
      presence of 0.5 % NaCl. A neighbour-joining phylogenetic tree based on 16S rRNA
      gene sequences showed that strain W-WS13T belonged to the genus Pedobacter,
      clustering robustly with the type strain of Pedobacter arcticus, sharing 95.9 %
      sequence similarity. Strain W-WS13T exhibited 16S rRNA gene sequence similarity
      of 90.1-95.6 % to the type strains of the other species of the genus Pedobacter.
      Strain W-WS13T contained MK-7 as the predominant menaquinone and iso-C15 : 0,
      summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c) and iso-C17 : 0 3-OH as
      the major fatty acids. The major polar lipid detected in strain W-WS13T was
      phosphatidylethanolamine. The DNA G+C content of strain W-WS13T was 36.9 mol%.
      Phylogenetic distinctiveness and differential phenotypic properties of strain W
      WS13T revealed that the novel strain is separated from recognized species of the
      genus Pedobacter. On the basis of the data presented, strain W-WS13T is
      considered to represent a novel species of the genus Pedobacter, for which the
      name Pedobacter lignilitoris sp. nov. is proposed. The type strain is W-WS13T ( =
      KCTC 42500T = CECT 8725T).

PMID- 26296664
TI  - Identification and characterization of conserved and variable regions of lime
      witches' broom phytoplasma genome.
AB  - Several segments (~20  kbp) of the lime witches' broom (LWB) phytoplasma genome
      (16SrII group) were sequenced and analysed. A 5.7  kbp segment (LWB-C) included
      conserved genes whose phylogenetic tree was consistent with that generated using
      16S rRNA genes. Another 6.4  kbp LWB phytoplasma genome segment (LWB-NC) was
      structurally similar to the putative mobile unit or sequence variable mosaic
      genomic region of phytoplasmas, although it represented a new arrangement of
      genes or pseudogenes such as phage-related protein genes and tra5 insertion
      sequences. Sequence- and phylogenetic-based evidence suggested that LWB-NC is a
      genomic region which includes horizontally transferred genes and could be
      regarded as a hot region to incorporate more foreign genes into the genome of LWB
      phytoplasma. The presence of phylogenetically related fragments of retroelements
      was also verified in the LWB phytoplasma genome. Putative intragenomic
      retrotransposition or retrohoming of these elements might have been determinant
      in shaping and manipulating the LWB phytoplasma genome. Altogether, the results
      of this study suggested that the genome of LWB phytoplasma is colonized by a
      variety of genes that have been acquired through horizontal gene transfer events,
      which may have further affected the genome through intragenomic mobility and
      insertion at cognate or incognate sites. Some of these genes are expected to have
      been involved in the development of features specific to LWB phytoplasma.

PMID- 26296665
TI  - Translation of the shallot virus X TGB3 gene depends on non-AUG initiation and
      leaky scanning.
AB  - Triple gene block (TGB), a conserved gene module found in the genomes of many
      filamentous and rod-shaped plant viruses, encodes three proteins, TGB1, TGB2 and
      TGB3, required for viral cell-to-cell movement through plasmodesmata and systemic
      transport via the phloem. The genome of Shallot virus X, the type species of the
      genus Allexivirus, includes TGB1 and TGB2 genes, but contains no canonical ORF
      for TGB3 protein. However, a TGB3-like protein-encoding sequence lacking an AUG
      initiator codon has been found in the shallot virus X (ShVX) genome in a position
      typical for TGB3 genes. This putative TGB3 gene is conserved in all
      allexiviruses. Here, we carried out sequence analysis to predict possible non-AUG
      initiator codons in the ShVX TGB3-encoding sequence. We further used an
      agroinfiltration assay in Nicotiana benthamiana to confirm this prediction. Site
      directed mutagenesis was used to demonstrate that the ShVX TGB3 could be
      translated on a bicistronic mRNA template via a leaky scanning mechanism. 

PMID- 26296666
TI  - What's the host and what's the microbe? The Marjory Stephenson Prize Lecture
      2015.
AB  - The interchange between retroviruses and their hosts is an intimate one because
      retroviruses integrate proviral DNA into host chromosomal DNA as an obligate step
      in the replication cycle. This has resulted in the occasional transduction of
      host genes into retroviral genomes as oncogenes, and also led to the integration
      of viral genomes into the host germ line that gives rise to endogenous
      retroviruses. I shall reflect on the evolutionary consequences of these events
      for virus and host. Then, I shall discuss the emergence of non-viral infections
      of host origin, namely, how malignant cells can give rise to eukaryotic single
      cell 'parasites' that colonize new hosts and how these in turn have been
      colonized by host mitochondria. 

PMID- 26296667
TI  - Mesorhizobium acaciae sp. nov., isolated from root nodules of Acacia melanoxylon
      R. Br.
AB  - Three novel strains, RITF741T, RITF1220 and RITF909, isolated from root nodules
      of Acacia melanoxylon in Guangdong Province of China, have been previously
      identified as members of the genus Mesorhizobium, displaying the same 16S rRNA
      gene RFLP pattern. Phylogenetic analysis of 16S rRNA gene sequences indicated
      that the three strains belong to the genus Mesorhizobium and had highest
      similarity (100.0 %) to Mesorhizobium plurifarium LMG 11892T. Phylogenetic
      analyses of housekeeping genes recA, atpD and glnII revealed that these strains
      represented a distinct evolutionary lineage within the genus Mesorhizobium.
      Strain RITF741T showed >73 % DNA-DNA relatedness with strains RITF1220 and
      RITF909, but < 60 % DNA-DNA relatedness with the closest type strains of
      recognized species of the genus Mesorhizobium. They differed from each other and
      from their closest phylogenetic neighbours by presence/absence of several fatty
      acids, or by large differences in the relative amounts of particular fatty acids.
      While showing distinctive features, they were generally able to utilize a wide
      range of substrates as sole carbon sources based on API 50CH and API 20NE tests.
      The three strains were able to form nodules with the original host Acacia
      melanoxylon and other woody legumes such as Acacia aneura, Albizia falcataria and
      Leucaena leucocephala. In conclusion, these strains represent a novel species
      belonging to the genus Mesorhizobium based on the data obtained in the present
      and previous studies, for which the name Mesorhizobium acaciae sp. nov. is
      proposed. The type strain is RITF741T ( = CCBAU 101090T = JCM 30534T), the DNA
      G+C content of which is 64.1 mol% (T m).

PMID- 26296668
TI  - Synergistic effects of ceftriaxone and erythropoietin on neuronal and behavioral
      deficits in an MPTP-induced animal model of Parkinson's disease dementia.
AB  - Both ceftriaxone (CEF) and erythropoietin (EPO) show neuroprotection and
      cognitive improvement in neurodegenerative disease. The present study was aimed
      at clarifying whether combined treatment with CEF and EPO (CEF+EPO) had superior
      neuroprotective and behavioral effects than treatment with CEF or EPO alone in a
      1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease
      (PD) rat model. The rats were injected with CEF (5 mg/kg/day), EPO (100
      IU/kg/day), or CEF+EPO after MPTP lesioning and underwent the bar-test, T-maze
      test, and object recognition test, then the brains were taken for histological
      evaluation. MPTP lesioning resulted in deficits in working memory and in object
      recognition, but the cognitive deficits were markedly reduced or eliminated in
      rats treated with CEF or CEF+EPO, with the combination having a greater effect.
      Lesioning also caused neurodegeneration in the nigrostriatal dopaminergic system
      and the hippocampal CA1 area and these changes were reduced or eliminated by
      treatment with CEF, EPO, or CEF+EPO, with the combination having a greater effect
      than single treatment in the densities of DAergic terminals in the striatum and
      neurons in the hippocampal CA1 area. Thus, compared to treatment with CEF or EPO
      alone, combined treatment with CEF+EPO had a greater inhibitory effect on the
      lesion-induced behavioral and neuronal deficits. To our knowledge, this is the
      first study showing a synergistic effect of CEF and EPO on neuroprotection and
      improvement in cognition in a PD rat model. Combined CEF and EPO treatment may
      have clinical potential for the treatment of the dementia associated with PD.

PMID- 26296669
TI  - Anxiolytic effect of neurotensin microinjection into the ventral pallidum.
AB  - Neurotensin (NT) acts as a neurotransmitter and neuromodulator in the central
      nervous system. NT is involved in reward and memory processes, drug addiction and
      also in the regulation of anxiety. The ventral pallidum (VP) receives
      neurotensinergic innervation from the ventral striatopallidal pathway originating
      from the nucleus accumbens. Positive reinforcing effects of NT in the VP had been
      shown recently, however the possible effects of NT on anxiety have not been
      examined yet. In our present experiments, the effects of NT on anxiety were
      investigated in the VP. In male Wistar rats bilateral microinjections of 100 ng
      or 250 ng NT were delivered in the volume of 0.4 MUl into the VP, and elevated
      plus maze (EPM) test was performed. In another groups of animals, 35 ng NT
      receptor 1 (NTR1) antagonist SR 48,692 was applied by itself, or microinjected 15
      min before 100 ng NT treatment. Open field test (OPF) was also conducted. The 100
      ng dose of NT had anxiolytic effect, but the 250 ng NT did not influence anxiety.
      The antagonist pretreatment inhibited the effect of NT, while the antagonist
      itself had no effect. In the OPF test there was no difference among the groups.
      Our present results show that microinjection of NT into the VP induces anxiolytic
      effect, which is specific to the NTR1 receptors because it can be eliminated by a
      specific NTR1 antagonist. It is also substantiated that neither the NT, nor the
      NTR1 antagonist in the VP influences locomotor activity.

PMID- 26296671
TI  - [Achilles tendon xanthoma].

PMID- 26296670
TI  - The importance of lactic acid in migraines and fibromyalgia.
AB  - BACKGROUND: Lactic acid is a byproduct of both muscle metabolism and the central
      nervous system. Changes in metabolism are related to various physiological and
      pathological conditions. The aim of this study was to determine the relationship
      between migraine and fibromyalgia with the levels of lactic acid in the blood.
      METHODS: We study of 93 patients was divided into five groups: 1) patients with
      fibromyalgia (n=20); 2) episodic migraine (n=20); 3) chronic migraine (n=20); 4)
      fibromyalgia and episodic migraine (n= 13); and 5) fibromyalgia and chronic
      migraine (n=20), and 20 healthy subjects (control group). Blood levels of lactic
      acid were measured at four different time points: at rest, during aerobic
      exercise, during anaerobic physical activity and while resting after anaerobic
      exercise. RESULTS: Lactic acid increased in all groups during anaerobic physical
      activity without predominance for either group. During aerobic physical activity,
      all groups increased lactic acid levels, but the increase was more expressive in
      the chronic migraine group and the chronic migraine with fibromyalgia group
      without statistical significance. CONCLUSIONS: We did not found abnormalities
      involving the metabolism of lactic acid in episodic and chronic migraine with or
      without fibromyalgia.

PMID- 26296672
TI  - Initial Evaluation of the Safety of Nanoshell-Directed Photothermal Therapy in
      the Treatment of Prostate Disease.
AB  - To evaluate the clinical safety profile for the use of gold nanoshells in
      patients with human prostate cancer. This follows on the nonclinical safety
      assessment of the AuroShell particles reported previously. Twenty-two patients,
      with biopsy diagnosed prostate cancer, underwent nanoshell infusion and
      subsequent radical prostatectomy (RRP). Fifteen of these patients had prostates
      that were additionally irradiated by a single-fiber laser ablation in each
      prostate hemisphere prior to RRP. Patients in the study were assessed at 9 time
      points through 6 months postinfusion. Adverse events were recorded as reported by
      the patients and from clinical observation. Blood and urine samples were
      collected at each patient visit and subjected to chemical (16 tests),
      hematological (23 tests), immunological (3 tests, including total PSA), and
      urinalysis (8 tests) evaluation. Temperature of the anterior rectal wall at the
      level of the prostate was measured. The study, recorded 2 adverse events that
      were judged attributable to the nanoparticle infusion: (1) an allergic reaction
      resulting in itching, which resolved with intravenous antihistamines, and (2) in
      a separate patient, a transient burning sensation in the epigastrium.
      blood/hematology/urinalysis assays indicated no device-related changes. No change
      in temperature of the anterior rectal wall was recorded in any of the patients.
      The clinical safety profile of AuroShell particles is excellent, matching
      nonclinical findings. A recent consensus statement suggested that the published
      literature does not support a preference for any ablation technique over
      another.(1) Now that clinical safety has been confirmed, treatment efficacy of
      the combined infusion plus laser ablation in prostate will be evaluated in future
      studies using imaging modalities directing the laser against identified prostate
      tumors. 

PMID- 26296673
TI  - Description of Bartonella ancashensis sp. nov., isolated from the blood of two
      patients with verruga peruana.
AB  - Three novel isolates of the genus Bartonella were recovered from the blood of two
      patients enrolled in a clinical trial for the treatment of chronic stage
      Bartonella bacilliformis infection (verruga peruana) in Caraz, Ancash, Peru. The
      isolates were initially characterized by sequencing a fragment of the gltA gene,
      and found to be disparate from B. bacilliformis. The isolates were further
      characterized using phenotypic and genotypic methods, and found to be genetically
      identical to each other for the genes assessed, but distinct from any known
      species of the genus Bartonella, including the closest relative B. bacilliformis.
      Other characteristics of the isolates, including their morphology, microscopic
      and biochemical properties, and growth patterns, were consistent with members of
      the genus Bartonella. Based on these results, we conclude that these three
      isolates are members of a novel species of the genus Bartonella for which we
      propose the name Bartonella ancashensis sp. nov. (type strain 20.00T = ATCC BAA
      2694T = DSM 29364T).

PMID- 26296674
TI  - The mechanisms of action of deep brain stimulation and ideas for the future
      development.
AB  - Deep brain stimulation (DBS) has been used as a treatment of movement disorders
      such as Parkinson's disease, dystonia, and essential tremor for over twenty
      years, and is a promising treatment for depression and epilepsy. However, the
      exact mechanisms of action of DBS are still uncertain, although different
      theories have emerged. This review summarizes the current understanding in this
      field. Different modalities used to investigate DBS such as electrophysiological,
      imaging and biochemical studies have revealed different mechanisms of DBS. The
      mechanisms may also be different depending on the structure targeted, the disease
      condition or the animal model employed. DBS may inhibit the target neuronal
      networks but activate the efferent axons. It may suppress pathological rhythms or
      impose new rhythms associated with beneficial effects, and involves neuronal
      networks with widespread connections. Different neurotransmitter systems such as
      dopamine and GABA upregulation are involved in the effects of DBS. There are also
      technical advances to prolong the battery life and specific targeting based on
      new electrode designs with multiple contacts which have the ability to steer the
      current toward a specific direction. There is ongoing work in closed loop or
      adaptive DBS using neural oscillations to provide the feedback signals. These
      oscillations need to be better characterized in a wide variety of clinical
      settings in future studies. Individualization of DBS parameters based on neural
      oscillations may optimize the clinical benefits of DBS. 

PMID- 26296675
TI  - Domibacillus tundrae sp. nov., isolated from active layer soil of tussock tundra
      in Alaska, and emended description of the genus Domibacillus.
AB  - A novel Gram-stain-positive, spore-forming, aerobic, motile and rod-shaped
      bacterium designated strain PAMC 80007T was isolated from an active layer soil
      sample of Council, Alaska. Optimal growth of strain PAMC 80007T was observed at
      30  degrees C, pH 7.0 and in the presence of 2 % (w/v) NaCl. Phylogenetic
      analysis based on 16S rRNA gene sequence indicated that strain PAMC 80007T
      belonged to the genus Domibacillus. This strain was closely related to
      Domibacillus enclensis (98.3 %), Domibacillus robiginosus (98.3 %) and
      Domibacillus indicus (97.2 %). Genomic DNA G+C content was 43.5 mol% and genomic
      relatedness analyses based on the average nucleotide identity and the genome-to
      genome distance showed that strain PAMC 80007T is clearly distinguished from the
      closely related species of the genus Domibacillus. The major fatty acids (>5 %)
      were iso-C15 : 0 (24.7 %), C16 : 1omega11c (16.8 %), anteiso-C15 : 0 (16.5 %),
      C16 : 0 (15.6 %) and anteiso-C17 : 0 (8.7 %). The major respiratory isoprenoid
      quinones were menaquinone-6 (MK-6) and menaquinone-7 (MK-7), and the polar lipid
      profile contained diphosphatidylglycerol, phosphatidylglycerol,
      phosphoglycolipid, phospholipid and two unidentified lipids. meso-Diaminopimelic
      acid (type A1gamma) was present in the cell-wall peptidoglycan, and the major
      whole-cell sugar was ribose with a minor quantity of glucose. Results from a
      polyphasic study suggested that strain PAMC 80007T represents a novel species of
      the genus Domibacillus for which the name Domibacillus tundrae sp. nov. is
      proposed. The type strain is PAMC 80007T ( = JCM 30371T = KCTC 33549T = DSM
      29572T). An emended description of the genus Domibacillus is also provided. 

PMID- 26296676
TI  - Does visual augmented feedback reduce local dynamic stability while walking?
AB  - Augmented feedback is frequently used in gait training to efficiently correct
      specific gait patterns in patients with different disorders. The patients use
      this external augmented feedback to align actual movements in a way that
      predefined gait characteristics can be achieved. Voluntary changes of gait
      characteristics are reported to reduce local dynamic stability (LDS) which in
      turn is associated with increased risk of falling. The aim of this study was to
      evaluate the instantaneous effect of visual feedback, provided to help patients
      to correct frontal plane pelvis and trunk movements, on the LDS of pelvis and
      trunk. Kinematic gait data was captured in ten women with gait disorders. The
      effect of visual feedback on LDS, quantified with the largest Lyapunov exponent,
      of walking was examined. We found a significant decreased LDS (e.g. pelvis:
      p=.009) in our subjects when they were using visual augmented feedback. Our data
      suggest that the use of visual augmented feedback causes less stable gait
      patterns indicating a reduced ability to respond to small perturbations which
      might increase risk of falling. Therefore, researchers or clinicians who aim to
      correct gait patterns through real time based external augmented feedback should
      consider the potential negative effect on gait stability. It should be evaluated
      if the possible increased fall risk provoked by visual feedback exceeds possible
      increases in fall risk induced by conventional gait-retraining interventions. The
      external validity of the study is limited because of the low sample size and
      inhomogeneous group characteristics. Thus, further studies including homogeneous
      cohorts are required. 

PMID- 26296677
TI  - NDM-1-producing Acinetobacter baumannii ST85 now in Turkey, including one isolate
      from a Syrian refugee.
AB  - New Delhi metallo-beta-lactamase-1 (NDM-1), an acquired class B carbapenemase, is
      a significant clinical threat owing to the extended hydrolysis of beta-lactams
      including carbapenems. Here, to the best of our knowledge we describe for the
      first time in Turkey two NDM-1-producing Acinetobacter baumannii isolates
      recovered from intensive care unit patients. The presence of blaNDM-1 was
      detected by PCR and confirmed by sequencing. The clonal relationship was assessed
      by PFGE and multilocus sequence typing. Both isolates were positive for blaNDM-1
      and were attributed with the sequence type 85. One isolate was from a Syrian
      refugee, whereas the second was from a patient who had never travelled outside
      Turkey. Our findings confirmed that the rapid spread of NDM-1-producing Gram
      negative organisms could become a major challenge for the treatment and control
      of healthcare-associated infections in our geographical area. They suggest also
      that NDM-1-producing strains and/or their genetic determinants are probably being
      imported from Syria to neighbouring countries. 

PMID- 26296678
TI  - Full-length de novo assembly of RNA-seq data in pea (Pisum sativum L.) provides a
      gene expression atlas and gives insights into root nodulation in this species.
AB  - Next-generation sequencing technologies allow an almost exhaustive survey of the
      transcriptome, even in species with no available genome sequence. To produce a
      Unigene set representing most of the expressed genes of pea, 20 cDNA libraries
      produced from various plant tissues harvested at various developmental stages
      from plants grown under contrasting nitrogen conditions were sequenced. Around
      one billion reads and 100 Gb of sequence were de novo assembled. Following
      several steps of redundancy reduction, 46 099 contigs with N50 length of 1667 nt
      were identified. These constitute the 'Cameor' Unigene set. The high depth of
      sequencing allowed identification of rare transcripts and detected expression for
      approximately 80% of contigs in each library. The Unigene set is now available
      online (http://bios.dijon.inra.fr/FATAL/cgi/pscam.cgi), allowing (i) searches for
      pea orthologs of candidate genes based on gene sequences from other species, or
      based on annotation, (ii) determination of transcript expression patterns using
      various metrics, (iii) identification of uncharacterized genes with interesting
      patterns of expression, and (iv) comparison of gene ontology pathways between
      tissues. This resource has allowed identification of the pea orthologs of major
      nodulation genes characterized in recent years in model species, as a major step
      towards deciphering unresolved pea nodulation phenotypes. In addition to a
      remarkable conservation of the early transcriptome nodulation apparatus between
      pea and Medicago truncatula, some specific features were highlighted. The
      resource provides a reference for the pea exome, and will facilitate
      transcriptome and proteome approaches as well as SNP discovery in pea.

PMID- 26296679
TI  - Clinical characteristics of patients with relapsed multiple myeloma.
AB  - Although survival outcomes have improved over the last decade for patients with
      multiple myeloma (MM), few patients remain free of disease and most inevitably
      relapse. Selecting a treatment for patients with relapsed MM is challenging given
      the number and diversity of regimens patients may have previously received, which
      can affect subsequent therapeutic choices. Importantly, a number of patient- and
      disease-related factors can also have an effect on treatment choice, treatment
      efficacy, and tolerability; thus, an understanding of the heterogeneity of
      patients in the setting of relapsed MM is important for appropriate treatment
      selection. Here, we review select patient and disease characteristics reported in
      key interventional and observational studies in relapsed MM (including age, sex,
      race, and the presence of high-risk disease, renal impairment, or peripheral
      neuropathy at baseline) to examine common and disparate features of patients with
      relapsed MM. As therapeutic regimens can have varying efficacy and/or
      tolerability in patients depending on these factors, we also provide treatment
      recommendations for patients with select baseline characteristics. 

PMID- 26296680
TI  - Clinical Risk Score to Predict Pancreatic Fistula after Pancreatoduodenectomy:
      Independent External Validation for Open and Laparoscopic Approaches.
AB  - BACKGROUND: A clinical risk score for pancreatic fistula (CRS-PF) was recently
      reported to predict postoperative pancreatic fistula (POPF) after
      pancreatoduodenectomy (PD). An independent external validation has not been
      performed. Our hypothesis was that CRS-PF predicts POPF after both laparoscopic
      and open PD. STUDY DESIGN: The CRS-PF was calculated from a retrospective review
      of patients undergoing PD from January 2007 to February 2014. Postoperative
      pancreatic fistula was graded using International Study Group of Pancreatic
      Fistula criteria. Grade B and C leaks were defined as clinically significant.
      Performance was measured based on sensitivity, specificity, positive and negative
      predictive value, accuracy, and R(2). RESULTS: There were 808 patients who met
      inclusion criteria; 539 (66.7%) had open and 269 (33.3%) had laparoscopic PD. The
      CRS-PF was high risk in 134 patients, intermediate in 492, low in 135, and
      negligible in 47. Postoperative pancreatic fistula occurred in 191 (23.6%)
      patients (grade A, 3.8%; B, 14.2%; and C, 5.6%), and it increased with risk
      category (R(2) = 0.935 all, 0.898 open, and 0.968 laparoscopic). High and
      intermediate risk categories were combined and classified as "test positive," and
      negligible and low risk categories were combined and classified "test negative,"
      resulting in a CRS-PF with a sensitivity of 95% and a negative predictive value
      of 96% for predicting POPF. Contrary to previous studies, grade A POPF increased
      with increasing CRS-PF and POPF did not correlate with estimated blood loss (R(2)
      = 0.04). CONCLUSIONS: The CRS-PF was validated independently by predicting POPF
      for both laparoscopic and open PD. Predictive performance was at least as good
      for laparoscopic PD as for open PD. Lack of correlation with estimated blood loss
      suggests CRS-PF might be tailored for improved performance. The CRS-PF is a
      clinically useful tool for POPF risk stratification after PD and allows for
      targeted intra- and postoperative measures to address patients at increased risk.

PMID- 26296681
TI  - Compliance with Physical Therapy is a Key Determinant of Success of Thoracic
      Outlet Surgical Decompression.

PMID- 26296682
TI  - Physical Therapy in the Management of Patients with Neurogenic Thoracic Outlet
      Syndrome: In Reply to Gambhir and colleagues.

PMID- 26296683
TI  - Donor Age in Liver Transplantation: Donation after Circulatory Death.

PMID- 26296684
TI  - Liver Transplantation and Donor Age: In Reply to Detry.

PMID- 26296685
TI  - Thoracic Endovascular Aortic Repair with the Left Subclavian Artery Coverage: Why
      Not Save the Left Subclavian Artery?

PMID- 26296686
TI  - Surgical Wound Misclassification.

PMID- 26296687
TI  - Surgical Wound Misclassification: A Multicenter Evaluation: In Reply to Dodds and
      Dodds.

PMID- 26296689
TI  - The HFE genotype and a formulated diet controlling for iron status attenuate
      experimental cerebral malaria in mice.
AB  - Plasmodium falciparum infects approximately 500million individuals each year. A
      small but significant number of infections lead to complications such as cerebral
      malaria. Cerebral malaria is associated with myelin damage and neurological
      deficits in survivors, and iron status is thought to impact the outcome of
      infection. We evaluated whether a mouse model of experimental cerebral malaria
      with Plasmodium berghei ANKA strain was altered by dietary iron deficiency or
      genetic iron overload (H67D HFE). We found that H67D mice had increased survival
      over H67H (wild type) mice. Moreover, a specifically designed formulation diet
      increased survival regardless of whether the diet was iron deficient or iron
      adequate. To determine potential mechanisms underlying demyelination in
      experimental cerebral malaria, we measured Semaphorin4A (Sema4A) protein levels
      in the brain because we found it is cytotoxic to oligodendrocytes. Sema4A was
      increased in wild type mice that developed experimental cerebral malaria while
      consuming standard rodent chow, consistent with a decrease in myelin basic
      protein, an indicator of myelin integrity. The brains of iron deficient and H67D
      mice had lower levels of Sema4A. Myelin basic protein was decreased in brains of
      mice fed the iron deficient diet as has been previously reported. We also
      examined erythropoietin, which is under consideration for treatment of cerebral
      malaria, and IL-6, which is known to increase during infection. We found that
      plasma erythropoietin was elevated and IL-6 was low in H67D mice and in the mice
      fed the formulation diets. These data reveal a paradigm-shifting concept that
      maintaining iron status may not increase the mortality associated with malaria
      and provide a dietary strategy for further examination. Moreover, the data
      provide clues for exploring the mechanism to limit the co-morbidity associated
      with experimental cerebral malaria that appears to include decreased Sema4A in
      brain as well as elevated erythropoietin and lower IL-6 in plasma. 

PMID- 26296692
TI  - Correction.

PMID- 26296691
TI  - Cohnella collisoli sp. nov., isolated from lava forest soil.
AB  - A novel bacterial strain, NKM-5(T), was isolated from soil of a lava forest in
      Nokkome Oreum, Jeju, Republic of Korea. Cells of strain NKM-5(T) were Gram-stain
      positive, motile, endospore-forming, rod-shaped and oxidase- and catalase
      positive. Strain NKM-5(T) contained anteiso-C15 : 0 and iso-C16 : 0 as the major
      fatty acids; menaquinone-7 (MK-7) as the predominant isoprenoid quinone;
      diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, lysyl
      phosphatidylglycerol, an unidentified phospholipid and three unidentified
      aminophospholipids as the polar lipids; and meso-diaminopimelic acid as the
      diagnostic diamino acid in the cell-wall peptidoglycan. The DNA G+C content was
      48.3 mol%. Phylogenetic analysis, based on 16S rRNA gene sequencing, showed that
      strain NKM-5(T) was most closely related to Cohnella lupini RLAHU4B(T) (96.9%
      sequence similarity) and fell into a clade in the genus Cohnella. On the basis of
      phylogenetic, chemotaxonomic and phenotypic data, strain NKM-5(T) represents a
      novel species of the genus Cohnella, for which the name Cohnella collisoli sp.
      nov. is proposed. The type strain is NKM-5(T) ( = KCTC 33634(T) = CECT 8805(T)).

PMID- 26296690
TI  - Identification and evaluation of vaccine candidate antigens from the poultry red
      mite (Dermanyssus gallinae).
AB  - An aqueous extract of the haematophagous poultry ectoparasite, Dermanyssus
      gallinae, was subfractionated using anion exchange chromatography. Six of these
      subfractions were used to immunise hens and the blood from these hens was fed, in
      vitro, to poultry red mites. Mite mortality following these feeds was indicative
      of protective antigens in two of the subfractions, with the risks of mites dying
      being 3.1 and 3.7 times higher than in the control group (P<0.001). A combination
      of two-dimensional immunoblotting and immunoaffinity chromatography, using IgY
      from hens immunised with these subfractions, was used in concert with proteomic
      analyses to identify the strongest immunogenic proteins in each of these
      subfractions. Ten of the immunoreactive proteins were selected for assessment as
      vaccine candidates using the following criteria: intensity of immune recognition;
      likelihood of exposure of the antigen to the antibodies in a blood meal; proposed
      function and known vaccine potential of orthologous molecules. Recombinant
      versions of each of these 10 proteins were produced in Escherichia coli and were
      used to immunise hens. Subsequent in vitro feeding of mites on blood from these
      birds indicated that immunisation with Deg-SRP-1 (serpin), Deg-VIT-1
      (vitellogenin), Deg-HGP-1 (hemelipoglycoprotein) or Deg-PUF-1 (a protein of
      unknown function) resulted in significantly increased risk of mite death (1.7
      2.8times higher than in mites fed blood from control hens immunised with adjuvant
      only, P<0.001). The potential for using these antigens in a recombinant vaccine
      is discussed.

PMID- 26296693
TI  - Scientific Poster Abstracts Selected for the 2015 American Society for Preventive
      Cardiology Cardiovascular Disease Conference, July 31-August 2, 2015 Boca Raton,
      Florida.

PMID- 26296694
TI  - Nitric oxide accumulation and protein tyrosine nitration as a rapid and long
      distance signalling response to salt stress in sunflower seedlings.
AB  - Sensing of salt stress by sunflower seedlings accompanies temporal and spatial
      modulation of intracellular nitric oxide (NO) accumulation and protein tyrosine
      nitration as markers of nitrosative stress. Employing a novel NO-specific probe
      for NO localization (a copper derivative of 4-methoxy-2-(1H-naphtho(2,3
      d)imidazol-2-yl)phenol; MNIP-Cu) synthesized in author's laboratory,
      immunological analysis of tyrosine nitrated proteins by confocal laser scanning
      microscopy (CLSM) and Western blot analysis, these rapid signalling events have
      been investigated. MNIP-Cu reveals the distribution of NO in whole seedlings.
      Preferential and enhanced NO localization around oil bodies (OBs) in cotyledons
      within 48 h of salt-stressed seedlings exhibits rapid transport of nitrosative
      stress signal from roots to the cotyledons. Immunological analysis reveals
      enhanced gradient of tyrosine nitrated proteins in salt-stressed roots from tip
      to the differentiating zone and from columella to the deep-seated cells. Western
      blot analysis shows that at least eight major cytosolic proteins exhibit enhanced
      tyrosine nitration in seedling roots in response to salt stress. Present
      observations provide strong evidence for rapid NO accumulation in salt stressed
      sunflower seedling roots and cotyledons and its impact on enhanced tyrosine
      nitration of cytosolic and OB proteins, as a mechanism to provide longevity to
      OBs for seedling survival under the salt stress.

PMID- 26296695
TI  - Exploring Temporal Progression of Events Using Eye Tracking.
AB  - This study investigates the representation of the temporal progression of events
      by means of the causal change in a patient. Subjects were asked to verify the
      relationship between adjectives denoting a source and resulting feature of a
      patient. The features were presented either chronologically or inversely to a
      primed event context given by a verb (to cut: long-short vs. short-long). Effects
      on response time and on eye movement data show that the relationship between
      features presented chronologically is verified more easily than that between
      features presented inversely. Post hoc, however, we found that the effects of
      temporal order occurred only when subjects read the features more than once.
      Then, the relationship between the features is matched with the causal change
      implied by the event context (contextual strategy). When subjects read the
      features only once, subjects respond to the relationship between the features
      without taking into account the event context.

PMID- 26296697
TI  - Photodynamic therapy: Progress toward a scientific and clinical network in Latin
      America.
AB  - Cancer is one of the major challenges for Latin America health services, since
      the skin cancer is the most frequent lesion. This manuscript addresses an
      initiative for the treatment of basal cell carcinomas (BCC) by photodynamic
      therapy (PDT) based on a government-funded national program in Brazil. The
      program provides clinical training and facilitates access to drugs/equipment and
      significantly reduces PDT costs. It also lays foundations for the establishment
      of a Latin American research network to improve prevention, early detection and
      treatment of diseases. Centers have been established by direct contact
      (conferences, visits to healthcare facilities and official departments). A local
      training was divided into complementary theoretical and practical parts. This is
      an ongoing project that has involved 10 countries: Brazil, Bolivia Chile,
      Ecuador, El Salvador, Colombia, Cuba, Mexico, Peru and Venezuela, The initial
      results are encouraging and have provided assessment of Latin America patients
      relating, for example, the most common skin phototypes with incidence of BCC in
      such countries. The network is expected to produce relevant scientific
      information for PDT introduction in many countries. The experience acquired by
      local teams shall enable them to innovate PDT protocols and increase the number
      of skilled contributors/researchers to broaden knowledge on the ever-crescent PDT
      field in Latin America. The establishment of a collaboration network and
      introduction of other projects and experience exchange shall become an easier
      process with time. This PDT clinical research network is a start for the
      strengthening of Science in South Hemisphere countries. 

PMID- 26296696
TI  - Rescreening for genetic mutations using multi-gene panel testing in patients who
      previously underwent non-informative genetic screening.
AB  - OBJECTIVE: The availability of next-generation sequencing and identification of
      multiple cancer-related genes has caused a shift away from single gene testing
      towards multi-gene panel testing for hereditary cancer syndromes. However, the
      utility of panels in individuals who previously underwent non-informative genetic
      screening has yet to be evaluated. We aim to evaluate the use of rescreening and
      results of multi-gene panels in this rescreened population. METHODS: We reviewed
      the medical records for patients who had previously undergone genetic testing and
      then underwent multi-gene panel testing at a single institution between 9/2013
      and 11/2014. RESULTS: One hundred and twenty-seven patients with prior genetic
      testing underwent multi-gene panels. One hundred and four patients (82%) had a
      history of cancer and 118 (93%) had at least one family member with cancer. On
      primary testing, no pathogenic mutations were detected and 10 patients (8%) were
      found to have variants of uncertain significance (VUS). On repeat multi-gene
      panel testing, nine patients (7%) were found to have a pathogenic mutation and 53
      patients (42%) were VUS not identified on prior testing. CONCLUSIONS: Seven
      percent of patients with non-informative primary testing were found to have a
      pathogenic mutation with multi-gene panels, suggesting that there is a potential
      benefit to be gained from rescreening. However, 42% of patients were found to
      have new VUS with panels, a result that can cause patients anxiety without clear
      clinical implications.

PMID- 26296698
TI  - Mobile laboratory in Sierra Leone during outbreak of Ebola: practices and
      implications.

PMID- 26296699
TI  - Astrocyte pathology in Alexander disease causes a marked inflammatory
      environment.
AB  - Astrocytes and microglia are commonly involved in a wide variety of CNS
      pathologies. However, they are typically involved in a secondary response in
      which many cell types are affected simultaneously and therefore it is difficult
      to know their contributions to the pathology. Here, we show that pathological
      astrocytes in a mouse model of Alexander disease (AxD; GFAP (Tg);Gfap (+/R236H))
      cause a pronounced immune response. We have studied the inflammatory response in
      the hippocampus and spinal cord of these mice and have found marked microglial
      activation, which follows that of astrocytes in a spatial pathological
      progression, as shown by increased levels of Iba1 and microglial cell (Iba1+)
      density. RNA sequencing and subsequent gene ontology (GO) analysis revealed that
      a majority of the most upregulated genes in GFAP (Tg);Gfap (+/R236H) mice are
      directly associated with immune function and that cytokine and chemokine GO
      attributes represent nearly a third of the total immune attributes. Cytokine and
      chemokine analysis showed CXCL10 and CCL2 to be the most and earliest increased
      molecules, showing concentrations as high as EAE or stroke models. CXCL10 was
      localized exclusively to astrocytes while CCL2 was also present in microglia.
      Despite the high levels of CXCL10 and CCL2, T cell infiltration was mild and no B
      cells were found. Thus, mutations in GFAP are sufficient to trigger a profound
      inflammatory response. The cellular stress caused by the accumulation of GFAP
      likely leads to the production of inflammatory molecules and microglial
      activation. Examination of human AxD CNS tissues also revealed microglial
      activation and T cell infiltrates. Therefore, the inflammatory environment may
      play an important role in producing the neuronal dysfunction and seizures of AxD.

PMID- 26296700
TI  - CD147 promotes IKK/IkappaB/NF-kappaB pathway to resist TNF-induced apoptosis in
      rheumatoid arthritis synovial fibroblasts.
AB  - TNF is highly expressed in synovial tissue of rheumatoid arthritis (RA) patients,
      where it induces proinflammatory cytokine secretion. However, in other cases, TNF
      will cause cell death. Considering the abnormal proliferation and activation of
      rheumatoid arthritis synovioblasts, the proper rate of synovioblast apoptosis
      could possibly relieve arthritis. However, the mechanism mediating TNF-induced
      synovioblast survival versus cell death in RA is not fully understood. Our
      objective was to study the role of CD147 in TNF downstream pathway preference in
      RA synovioblasts. We found that overexpressing TNF in synovial tissue did not
      increase the apoptotic level and, in vitro, TNF-induced mild synovioblast
      apoptosis and promoted IL-6 secretion. CD147, which was highly expressed in
      rheumatoid arthritis synovial fibroblasts (RASFs), increased the resistance of
      synovioblasts to apoptosis under TNF stimulation. Downregulating CD147 both
      increased the apoptotic rate and inhibited IkappaB kinase (IKK)/IkappaB/NF-kappaB
      pathway-dependent proinflammatory cytokine secretion. Further, we determined that
      it was the extracellular portion of CD147 and not the intracellular portion that
      was responsible for synovioblast apoptosis resistance. CD147 monoclonal antibody
      inhibited TNF-induced proinflammatory cytokine production but had no effect on
      apoptotic rates. Thus, our study indicates that CD147 is resistant to TNF-induced
      apoptosis by promoting IKK/IkappaB/NF-kappaB pathway, and the extracellular
      portion of CD147 is the functional region. KEY MESSAGES: CD147 inhibits TNF
      stimulated RASF apoptosis. CD147 knockdown decreases IKK expression and inhibits
      NF-kappaB-related cytokine secretion. CD147's extracellular portion is
      responsible for apoptosis resistance. CD147 antibody inhibits TNF-related
      cytokine secretion without additional apoptosis.

PMID- 26296701
TI  - Exome sequencing reveals frequent deleterious germline variants in cancer
      susceptibility genes in women with invasive breast cancer undergoing neoadjuvant
      chemotherapy.
AB  - When sequencing blood and tumor samples to identify targetable somatic variants
      for cancer therapy, clinically relevant germline variants may be uncovered. We
      evaluated the prevalence of deleterious germline variants in cancer
      susceptibility genes in women with breast cancer referred for neoadjuvant
      chemotherapy and returned clinically actionable results to patients. Exome
      sequencing was performed on blood samples from women with invasive breast cancer
      referred for neoadjuvant chemotherapy. Germline variants within 142 hereditary
      cancer susceptibility genes were filtered and reviewed for pathogenicity. Return
      of results was offered to patients with deleterious variants in actionable genes
      if they were not aware of their result through clinical testing. 124 patients
      were enrolled (median age 51) with the following subtypes: triple negative (n =
      43, 34.7%), HER2+ (n = 37, 29.8%), luminal B (n = 31, 25%), and luminal A (n =
      13, 10.5%). Twenty-eight deleterious variants were identified in 26/124 (21.0%)
      patients in the following genes: ATM (n = 3), BLM (n = 1), BRCA1 (n = 4), BRCA2
      (n = 8), CHEK2 (n = 2), FANCA (n = 1), FANCI (n = 1), FANCL (n = 1), FANCM (n =
      1), FH (n = 1), MLH3 (n = 1), MUTYH (n = 2), PALB2 (n = 1), and WRN (n = 1).
      121/124 (97.6%) patients consented to return of research results. Thirteen
      (10.5%) had actionable variants, including four that were returned to patients
      and led to changes in medical management. Deleterious variants in cancer
      susceptibility genes are highly prevalent in patients with invasive breast cancer
      referred for neoadjuvant chemotherapy undergoing exome sequencing. Detection of
      these variants impacts medical management.

PMID- 26296702
TI  - Social Network Characteristics Moderate the Association Between Stigmatizing
      Attributions About HIV and Non-adherence Among Black Americans Living with HIV: a
      Longitudinal Assessment.
AB  - BACKGROUND: Stigma may contribute to HIV-related disparities among HIV-positive
      Black Americans. PURPOSE: We examined whether social network characteristics
      moderate stigma's effects. METHODS: At baseline and 6 months post-baseline, 147
      HIV-positive Black Americans on antiretroviral treatment completed egocentric
      social network assessments, from which we derived a structural social support
      capacity measure (i.e., ability to leverage support from the network, represented
      by the average interaction frequency between the participant and each alter).
      Stigma was operationalized with an indicator of whether any social network member
      had expressed stigmatizing attributions of blame or responsibility about HIV.
      Daily medication adherence was monitored electronically. RESULTS: In a
      multivariate regression, baseline stigma was significantly related to decreased
      adherence over time. The association between stigma and non-adherence was
      attenuated among participants who increased the frequency of their interactions
      with alters over time. CONCLUSIONS: Well-connected social networks have the
      potential to buffer the effects of stigma.

PMID- 26296703
TI  - Disease Messaging in Churches: Implications for Health in African-American
      Communities.
AB  - Using the right messaging strategies, churches can help promote behavior change.
      Frequencies of disease-specific messages in 21 African-American churches were
      compared to overall and cancer-specific mortality and morbidity rates as well as
      church-level variables. Disease messages were found in 1025 of 2166 items.
      Frequently referenced topics included cancer (n = 316), mental health conditions
      (n = 253), heart disease (n = 246), and infectious diseases (n = 220). Messages
      for lung and colorectal cancers appeared at low frequency despite high mortality
      rates in African-American communities. Season, church size, and denomination
      showed significant associations with health messages. Next steps include testing
      messaging strategies aimed at improving the health of churchgoing communities. 

PMID- 26296704
TI  - Cannabinoid receptor type 1 agonist ACEA improves motor recovery and protects
      neurons in ischemic stroke in mice.
AB  - Brain ischemia produces neuronal cell death and the recruitment of pro
      inflammatory cells. In turn, the search for neuroprotection against this type of
      insult has rendered results involving a beneficial role of endocannabinoid
      receptor agonists in the Central Nervous System. In this work, to further
      elucidate the mechanisms associated to this neuroprotective effect, focal brain
      ischemia was generated by middle cerebral artery occlusion (MCAo) in C57Bl/6
      mice. Three, 24 and 48 h after MCAo, animals received CB1R agonist ACEA (1
      mg/kg), CB1R antagonist AM251 (1 mg/kg) or vehicle. To assess motor activity,
      neural deficit scores and motor tests were performed 1 day before and 3, 7, 14,
      21, and 28 days after MCAo. At 7 and 28 days post lesion, cytoskeleton structure,
      astroglial and microglial reaction, and alterations in synapsis were studied in
      the cerebral cortex. ACEA treatment reduced astrocytic reaction, neuronal death,
      and dendritic loss. In contrast, AM251 treatment increased these parameters.
      Motor tests showed a progressive deterioration in motor activity in ischemic
      animals, which only ACEA treatment was able to counteract. Our results suggest
      that CB1R may be involved in neuronal survival and in the regulation of
      neuroprotection during focal cerebral ischemia in mice.

PMID- 26296705
TI  - Insights into teichoic acid biosynthesis by Bifidobacterium bifidum PRL2010.
AB  - Bifidobacteria are colonizers of the human gut, where they are interacting with
      their host as well as with other members of the intestinal microbiota. Teichoic
      acids (TAs) have previously been shown to play an important role in modulating
      microbe-host interactions in the human gut. However, so far, there is a paucity
      of information regarding the presence of TAs in the cell envelope of
      bifidobacteria. In silico analyses targeting the chromosomes of all 48
      (sub)species that currently represent the genus Bifidobacterium revealed the
      presence of genes responsible for TA biosynthesis, suggesting that bifidobacteria
      contain both wall TAs and lipoteichoic acids. Transcriptome analyses of the
      infant gut commensal Bifidobacterium bifidum PRL2010 highlighted that the
      transcription of the presumptive TA biosynthetic loci is modulated in response to
      environmental conditions reflecting those of the human gut. Furthermore, chemical
      characterization of TAs produced by PRL2010 indicates the presence of
      lipoteichoic acids. 

PMID- 26296706
TI  - Biogenesis of Lysobacter sp. XL1 vesicles.
AB  - The Gram-negative bacterium Lysobacter sp. XL1 forms vesicles and, using them,
      secretes an extracellular protein, bacteriolytic endopeptidase L5. Fractionation
      of a Lysobacter sp. XL1 vesicle preparation in a sucrose density gradient yielded
      four vesicle fractions of 30%, 35%, 40% and 45% sucrose. The size of most
      vesicles concentrated in 30% and 35% sucrose fractions were 40-65 and 65-100 nm,
      respectively. Electrophoresis and immunoblotting showed vesicles of the 30%
      fraction differed from those in the other fractions not only in density but also
      in protein content. Protein L5 was found to be secreted into the extracellular
      medium only by means of vesicles of the 30% sucrose fraction. Electron
      microscopic immunocytochemistry of Lysobacter sp. XL1 cells showed protein L5 to
      be distributed unevenly along the periplasmic space and to be concentrated in
      certain periplasmic loci adjacent to the outer membrane. It was in those loci
      where vesiculation occurred. A model of the formation of Lysobacter sp. XL1
      vesicles is proposed based on the data obtained. 

PMID- 26296707
TI  - A revision of the history of the Colletotrichum acutatum species complex in the
      Nordic countries based on herbarium specimens.
AB  - Herbaria collections containing plants with disease symptoms are highly valuable,
      and they are often the only way to investigate outbreaks and epidemics from the
      past as the number of viable isolates in culture collections is often limited.
      Species belonging to the Colletotrichum acutatum complex infect a range of
      important crops. As members of the C. acutatum complex are easily confused with
      other Colletotrichum species, molecular methods are central for the correct
      identification. We performed molecular analyses on 21 herbaria specimens,
      displaying anthracnose symptoms, collected in Norway and Denmark before the first
      confirmed findings of C. acutatum complex members in this region. Sequencing
      parts of the fungal ITS regions showed that members of the species complex were
      present in 13 of the 21 specimens collected in different parts of Norway and
      Denmark between 1948 and 1991, representing seven plant hosts (three cherry
      species, apple, raspberry and rhododendron). This is the first time herbarium
      specimens have been used to study these pathogens under Nordic conditions.
      Differences in the ITS sequences suggest the presence of different genotypes
      within the complex, indicating a well-established population. 

PMID- 26296708
TI  - P450-Based Drug-Drug Interactions of Amiodarone and its Metabolites: Diversity of
      Inhibitory Mechanisms.
AB  - In this study, IC50 shift and time-dependent inhibition (TDI) experiments were
      carried out to measure the ability of amiodarone (AMIO), and its circulating
      human metabolites, to reversibly and irreversibly inhibit CYP1A2, CYP2C9, CYP2D6,
      and CYP3A4 activities in human liver microsomes. The [I]u/Ki,u values were
      calculated and used to predict in vivo AMIO drug-drug interactions (DDIs) for
      pharmaceuticals metabolized by these four enzymes. Based on these values, the
      minor metabolite N,N-didesethylamiodarone (DDEA) is predicted to be the major
      cause of DDIs with xenobiotics primarily metabolized by CYP1A2, CYP2C9, or
      CYP3A4, while AMIO and its N-monodesethylamiodarone (MDEA) derivative are the
      most likely cause of interactions involving inhibition of CYP2D6 metabolism. AMIO
      drug interactions predicted from the reversible inhibition of the four P450
      activities were found to be in good agreement with the magnitude of reported
      clinical DDIs with lidocaine, warfarin, metoprolol, and simvastatin. The TDI
      experiments showed DDEA to be a potent inactivator of CYP1A2 (KI = 0.46 MUM,
      kinact = 0.030 minute(-1)), while MDEA was a moderate inactivator of both CYP2D6
      (KI = 2.7 MUM, kinact = 0.018 minute(-1)) and CYP3A4 (KI = 2.6 MUM, kinact =
      0.016 minute(-1)). For DDEA and MDEA, mechanism-based inactivation appears to
      occur through formation of a metabolic intermediate complex. Additional metabolic
      studies strongly suggest that CYP3A4 is the primary microsomal enzyme involved in
      the metabolism of AMIO to both MDEA and DDEA. In summary, these studies
      demonstrate both the diversity of inhibitory mechanisms with AMIO and the need to
      consider metabolites as the culprit in inhibitory P450-based DDIs. 

PMID- 26296710
TI  - New Photosafety Assessment Strategy Based on the Photochemical and
      Pharmacokinetic Properties of Both Parent Chemicals and Metabolites.
AB  - Photoreactivity and dermal/ocular deposition of compounds have been recognized as
      key considerations for evaluating the phototoxic risk of compounds. Because some
      drugs are known to cause phototoxic reactions via generation of potent phototoxic
      metabolites, photosafety assessments on parent drugs alone may lead to false
      predictions about their photosafety. This study aimed to establish a new
      photosafety assessment strategy for evaluating the in vivo phototoxic potential
      of both a parent substance and its metabolites. The in vivo phototoxic risk of
      fenofibrate (FF) and its metabolites, fenofibric acid (FA) and reduced fenofibric
      acid, were evaluated based on photochemical and pharmacokinetic analyses. FF and
      FA exhibited intensive UV absorption, with molar extinction coefficient values of
      17,000 (290 nm) and 14,000 M(-1)cm(-1) (295 nm), respectively. Superoxide
      generation from FA was significantly higher than from FF, and a marked increase
      in superoxide generation from FF was observed after incubation with rat hepatic
      S9 fractions, suggesting enhanced photoreactivity of FF after metabolism. FA
      showed high dermal/ocular deposition after oral administration (5 mg/kg, p.o.)
      although the concentration of FF was negligible, suggesting high exposure risk
      from FA. On the basis of these findings, FA was deduced to be a major contributor
      to phototoxicity induced by FF taken orally, and this prediction was in
      accordance with the results from in vitro/in vivo phototoxicity tests. Results
      from this study suggest that this new screening strategy for parent substances
      and their metabolites provides reliable photosafety information on drug
      candidates and would be useful for drug development with wide safety margins. 

PMID- 26296709
TI  - Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulation Approaches:
      A Systematic Review of Published Models, Applications, and Model Verification.
AB  - Modeling and simulation of drug disposition has emerged as an important tool in
      drug development, clinical study design and regulatory review, and the number of
      physiologically based pharmacokinetic (PBPK) modeling related publications and
      regulatory submissions have risen dramatically in recent years. However, the
      extent of use of PBPK modeling by researchers, and the public availability of
      models has not been systematically evaluated. This review evaluates PBPK-related
      publications to 1) identify the common applications of PBPK modeling; 2)
      determine ways in which models are developed; 3) establish how model quality is
      assessed; and 4) provide a list of publically available PBPK models for sensitive
      P450 and transporter substrates as well as selective inhibitors and inducers.
      PubMed searches were conducted using the terms "PBPK" and "physiologically based
      pharmacokinetic model" to collect published models. Only papers on PBPK modeling
      of pharmaceutical agents in humans published in English between 2008 and May 2015
      were reviewed. A total of 366 PBPK-related articles met the search criteria, with
      the number of articles published per year rising steadily. Published models were
      most commonly used for drug-drug interaction predictions (28%), followed by
      interindividual variability and general clinical pharmacokinetic predictions
      (23%), formulation or absorption modeling (12%), and predicting age-related
      changes in pharmacokinetics and disposition (10%). In total, 106 models of
      sensitive substrates, inhibitors, and inducers were identified. An in-depth
      analysis of the model development and verification revealed a lack of consistency
      in model development and quality assessment practices, demonstrating a need for
      development of best-practice guidelines. 

PMID- 26296712
TI  - Congenital adrenal hyperplasia cases identified by newborn screening in one- and
      two-screen states.
AB  - There is no clear consensus among state newborn screening programs on whether
      routine second screening of newborns identifies clinically relevant cases of
      congenital adrenal hyperplasia. This retrospective study evaluated laboratory
      practices, along with biochemical and medical characteristics of congenital
      adrenal hyperplasia (CAH) cases (1) detected on the first newborn screen in one
      screen compared to two-screen states, and (2) detected on the first versus the
      second screen in the two-screen states, to determine the effectiveness of a
      second screen. A total of 374 confirmed cases of CAH from 2 one-screen states and
      5 two-screen states were included in this study. Demographic data and diagnostic
      information on each reported case were collected and analyzed. Additionally,
      laboratory data, including screening methodologies and algorithms, were
      evaluated. The one-screen states reported 99 cases of CAH out of 1,740,586 (1 in
      17,500) newborns screened: 88 (89%) identified on the first screen and 5 (5%)
      identified on the targeted second screen. The two-screen states reported 275
      cases of CAH out of 2,629,627 (1 in 9500) newborns screened: 165 (60%) identified
      on the first screen and 99 (36%) identified on the second screen. Using a
      multivariate model, the only significant predictor of whether a case was
      identified on the first or the second screen in the two-screen states was the
      type of CAH. Compared with classical salt-wasting CAH, classical simple
      virilizing and non-classical CAH cases were less likely to be detected on the
      first versus the second screen. The routine second newborn screen is important
      for identifying children with CAH, particularly simple virilizing and non
      classical forms, which might otherwise not be captured through a single screen. 

PMID- 26296713
TI  - Emerging morphologies in round bacterial colonies: comparing volumetric versus
      chemotactic expansion.
AB  - Biological experiments performed on living bacterial colonies have demonstrated
      the microbial capability to develop finger-like shapes and highly irregular
      contours, even starting from an homogeneous inoculum. In this work, we study from
      the continuum mechanics viewpoint the emergence of such branched morphologies in
      an initially circular colony expanding on the top of a Petri dish coated with
      agar. The bacterial colony expansion, based on either a source term, representing
      volumetric mitotic processes, or a nonconvective mass flux, describing
      chemotactic expansion, is modeled at the continuum scale. We demonstrate that the
      front of the colony is always linearly unstable, having similar dispersion curves
      to the ones characterizing branching instabilities. We also perform finite
      element simulations, which not only prove the emergence of branching, but also
      highlight dramatic differences between the two mechanisms of colony expansion in
      the nonlinear regime. Furthermore, the proposed combination of analytical and
      numerical analysis allowed studying the influence of different model parameters
      on the selection of specific patterns. A very good agreement has been found
      between the resulting simulations and the typical structures observed in
      biological assays. Finally, this work provides a new interpretation of the
      emergence of branched patterns in living aggregates, depicted as the results of a
      complex interplay among chemical, mechanical and size effects.

PMID- 26296711
TI  - Self-reported treatment-associated symptoms among patients with urea cycle
      disorders participating in glycerol phenylbutyrate clinical trials.
AB  - BACKGROUND: Health care outcomes have been increasingly assessed through health
      related quality of life (HRQoL) measures. While the introduction of nitrogen
      scavenging medications has improved survival in patients with urea cycle
      disorders (UCDs), they are often associated with side effects that may affect
      patient compliance and outcomes. METHODS: Symptoms commonly associated with
      nitrogen-scavenging medications were evaluated in 100 adult and pediatric
      participants using a non-validated UCD-specific questionnaire. Patients or their
      caregivers responded to a pre-defined list of symptoms known to be associated
      with the use of these medications. Responses were collected at baseline (while
      patients were receiving sodium phenylbutyrate [NaPBA]) and during treatment with
      glycerol phenylbutyrate (GPB). RESULTS: After 3 months of GPB dosing, there were
      significant reductions in the proportion of patients with treatment-associated
      symptoms (69% vs. 46%; p<0.0001), the number of symptoms per patient (2.5 vs.
      1.1; p<0.0001), and frequency of the more commonly reported individual symptoms
      such as body odor, abdominal pain, nausea, burning sensation in mouth, vomiting,
      and heartburn (p<0.05). The reduction in symptoms was observed in both pediatric
      and adult patients. The presence or absence of symptoms or change in severity did
      not correlate with plasma ammonia levels or NaPBA dose. CONCLUSIONS: The
      reduction in symptoms following 3 months of open-label GPB dosing was similar in
      pediatric and adult patients and may be related to chemical structure and
      intrinsic characteristics of the product rather than its effect on ammonia
      control.

PMID- 26296714
TI  - Effect of Substituents in Catechol Dye Sensitizers on Photovoltaic Performance of
      Type II Dye-Sensitized Solar Cells.
AB  - In order to provide a direction in molecular design of catechol (Cat) dyes for
      type II dye-sensitized solar cells (DSSCs), the dye-to-TiO2 charge-transfer
      (DTCT) characteristics of Cat dyes with various substituents and their
      photovoltaic performance in DSSCs are investigated. The Cat dyes with electron
      donating or moderately electron-withdrawing substituents exhibit a broad
      absorption band corresponding to DTCT upon binding to TiO2 films, whereas those
      with strongly electron-withdrawing substituents exhibit weak DTCT. This study
      indicates that the introduction of a moderately electron-withdrawing substituent
      on the Cat moiety leads to not only an increase in the DTCT efficiency, but also
      the retardation of back electron transfer. This results in favorable conditions
      for the type II electron-injection pathway from the ground state of the Cat dye
      to the conduction band of the TiO2 electrode by the photoexcitation of DTCT
      bands. 

PMID- 26296715
TI  - Anaphylactic Reaction to Methylprednisolone.

PMID- 26296716
TI  - What's In Your Kit? A Safety Checkup May Be In Order.

PMID- 26296717
TI  - The Impact of a Flexible Care Area on Throughput Measures in an Academic
      Emergency Department.
AB  - INTRODUCTION: Crowding in emergency departments is a multifaceted problem. We
      hypothesized that implementing an on-call "Flexible Care Area" (FCA), utilizing
      multiple front-end throughput solutions, would reduce ED length of stay (LOS).
      METHODS: This retrospective study evaluates the impact of an FCA on ED throughput
      at one hospital over a 2-year period (2011-2012). The average arrival-to-room
      time, arrival-to-physician time, LOS, number of inpatient admissions, and number
      of discharges during FCA hours were collected, and days with and without FCA
      functionality were compared. RESULTS: The FCA was open 165 days in 2011 and 252
      days in 2012. The mean daily ED census, as well as the number of ED visits and
      inpatient admissions during FCA hours, were higher on days with FCA functionality
      than on days without FCA functionality. Total ED LOS was shorter for Emergency
      Severity Index (ESI) level 3 patients on days with FCA than on days without it in
      2011, but this finding was not repeated in 2012. ESI level 4 patients had shorter
      LOS on FCA days in both years. The arrival-to-room and arrival-to-physician times
      showed variable improvement for ESI level 3 and 4 patients over the study period.
      No statistically significant difference for these measures was found when
      evaluating ESI levels 2 and 5. DISCUSSION: Implementing upfront throughput
      solutions through use of the FCA correlated with reduced ED LOS for all ESI level
      3 and 4 patients, not just those who were seen in the FCA.

PMID- 26296718
TI  - A Biophysical and Economic Profile of South Georgia and the South Sandwich
      Islands as Potential Large-Scale Antarctic Protected Areas.
AB  - The current hiatus in the establishment of a network of marine protected areas
      (MPAs) in the Antarctic means that other routes to conservation are required. The
      protection of overseas territories in the Antarctic and sub-Antarctic represents
      one way to advance the initiation of such a network. This review of the physical
      and biological features of the United Kingdom (U.K.) overseas territories of
      South Georgia and South Sandwich Islands (SGSSI) is undertaken to estimate the
      importance of the islands in terms of marine conservation in the Southern Ocean
      and globally. The economy and management of SGSSI are also analysed, and the
      question of whether the islands already have sufficient protection to constitute
      part of an Antarctic network of MPAs is assessed. The SGSSI comprise unique
      geological and physical features, a diverse marine biota, including a significant
      proportion of endemic species and globally important breeding populations of
      marine predators. Regardless of past exploitation of biotic resources, such as
      seals, whales and finfish, SGSSI would make a significant contribution to
      biological diversity in an Antarctic network of MPAs. At present, conservation
      measures do not adequately protect all of the biological features that render the
      islands so important in terms of conservation at a regional and global level.
      However, a general lack of data on Antarctic marine ecosystems (particularly
      needed for SGSSSI) makes it difficult to assess this fully. One barrier to
      achieving more complete protection is the continuing emphasis on fishing effort
      in these waters by U.K. government. Other non-U.K. Antarctic overseas territories
      of conservation importance are also compromised as MPAs because of the
      exploitation of fisheries resources in their waters. The possible non-use values
      of SGSSI as well as the importance of ecosystem services that are indirectly used
      by people are outlined in this review. Technology is improving the potential for
      management of remote MPAs, particularly in the context of incursion by illegal
      fishing activities and use of satellite surveillance for enforcement of fisheries
      and conservation regulations. The conflict between commercial exploitation and
      conservation of Antarctic marine living resources is explored. 

PMID- 26296719
TI  - Dentin tubule invasion by Enterococcus faecalis under stress conditions ex vivo.
AB  - Enterococcus faecalis is the species most frequently isolated from failed
      endodontic treatments because it can survive under stress conditions imposed by
      root canal treatment. The objective of this study was to determine the ability of
      E. faecalis to invade dentine tubules under alkaline and energy-starvation stress
      and to explore the potential mechanisms. Roots from single-rooted human teeth
      were infected with E. faecalis under alkaline and energy-starvation stress
      conditions. After 4 wk of culture, samples were processed to establish the tubule
      penetration distance. In addition, the hydrophobicity of E. faecalis cells under
      these conditions was analysed and the expression of genes involved in adhesion
      was quantified by real-time quantitative PCR. Culture of E. faecalis under
      alkaline and energy-starvation stress conditions resulted in a marked reduction
      of tubule-penetration distance, a significant increase in hydrophobicity of the
      bacterial surface, and marked down-regulation of most adhesin genes compared with
      E. faecalis cultured in tryptic soy broth. The results indicate that the dentine
      tubule invasion ability of E. faecalis was markedly decreased under alkaline and
      glucose-starvation stress conditions, possibly because of the increase of
      hydrophobicity and down-regulation of some adhesion genes.

PMID- 26296720
TI  - Effects of proton pump inhibitor on outcomes of patients with severe acute
      pancreatitis based on a national administrative database.
AB  - OBJECTIVE: This study aimed to investigate whether proton pump inhibitors (PPIs)
      affect the outcomes of patients with severe acute pancreatitis based on a
      national administrative database. METHODS: A total of 10,400 patients with severe
      acute pancreatitis were referred to 1021 hospitals between 2010 and 2012 in
      Japan. Patients were divided into two groups: patients who used PPIs (n = 3879)
      and those without PPIs (n = 6521). We collected patients' data from the
      administrative database to compare in-hospital mortality within 7, 14, and 28
      days, and overall in-hospital mortality between groups, using propensity score
      analysis to adjust for treatment selection bias. RESULTS: Multiple logistic
      regression showed that use of PPIs did not affect in-hospital mortality within 7
      and 14 days. The odds ratio (OR) for mortality within 7 days was 1.14 (95%
      confidence interval [CI]: 0.91-1.42, p = 0.236) while that within 14 days was
      1.10 (95% CI: 0.89-1.35, p = 0.349). No significant association was observed for
      in-hospital mortality within 28 days and overall in-hospital mortality (OR for
      within 28 days: 1.12, 95% CI: 0.92-1.37, p = 0.224; OR for overall in-hospital
      mortality: 1.42, 95% CI: 0.97-1.87, p = 0.065). CONCLUSIONS: This study shows
      that use of PPIs does not affect clinical outcomes of patients with severe acute
      pancreatitis. Prospective or randomized studies are needed to confirm the
      efficacy of PPIs on outcomes of patients with severe acute pancreatitis in the
      future.

PMID- 26296721
TI  - Rice grassy stunt virus nonstructural protein p5 serves as a viral suppressor of
      RNA silencing and interacts with nonstructural protein p3.
AB  - Rice grassy stunt virus (RGSV), a member of the genus Tenuivirus, causes serious
      rice disease in Southeast Asian countries. In this study, a green fluorescent
      protein (GFP)-based transient expression assay was conducted to show that p5,
      encoded on RNA5 in the viral sense, is a viral suppressor of RNA silencing (VSR).
      Protein-protein interactions (PPIs) between p5 and all RGSV proteins except pC1
      and pC2 were investigated using Gal4-based yeast two-hybrid (Y2H) experiments.
      The results demonstrated that p5 interacts with itself and with p3 encoded on
      RNA3 in the viral sense. p5-p5 and p5-p3 interactions were detected by
      bimolecular fluorescence complementation (BiFC) assay, and the p5-p3 interaction
      was confirmed by subcellular co-localization and co-immunoprecipitation (Co-IP)
      assays. Using the Y2H system, we demonstrated that the p5-p3 interaction requires
      both the N-terminal (amino acid residues 1 to 99) and C-terminal (amino acid
      residues 94 to 191) domains of p5. In addition, either p5 or p3 could enhance the
      pathogenicity of potato virus X (PVX) in Nicotiana benthamiana plants. A much
      more significant enhancement of PVX pathogenicity and accumulation was observed
      when p5 and p3 were expressed together. Our data also showed that RGSV p3 does
      not function as a VSR, and it had no effect on the VSR activity of p5 or the
      subcellular localization pattern of p5 in plant cells from Nicotiana benthamiana.

PMID- 26296722
TI  - Family history influences clinical course of idiopathic calcium nephrolithiasis:
      case-control study of a large cohort of Italian patients.
AB  - AIM: To evaluate the contribution of family history of stones (FHS), up to second
      degree relatives, on clinical course (age of first renal colic, bilateral
      disease, retained calculi, recurrences, urological procedures) of idiopathic
      calcium nephrolithiasis (ICN) and urinary parameters of lithogenic risk, a case
      control study was carried out. METHOD: Clinical records of 2080 patients with ICN
      were evaluated and categorized according to FHS. Data about clinical course of
      disease and urinary parameters of lithogenic risk were collected. Student's t,
      Chi square tests and binary logistic regression were applied to discriminate
      groups with vs. without FHS. RESULTS: FHS was associated with an earlier onset of
      stone disease (age at first episode 32 +/- 13 vs. 37 +/- 15 years, p <0.001),
      particularly in females. After adjustment for multiple covariates, FHS was
      significantly associated to a higher risk of recurrence [odds ratio (OR) 1.2, 95
      % confidence interval (1.1-1.4), p = 0.04], retained stones [OR 1.3, CI (1.1
      1.5), p = 0.004], bilateral stones [OR 1.2, 95 % CI (1.1-1.5), p = 0.022] and
      urological procedures [OR 1.2, 95 % CI (1.1-1.5), p = 0.034]. FHS did not
      influence urinary parameters of lithogenic risk, except for calcium excretion in
      females. CONCLUSION: A positive family history influences the clinical course of
      ICN with some significant gender-related differences, substantially irrespective
      of urinary parameters of lithogenic risk.

PMID- 26296723
TI  - Evolutionary aspects of emerging Lyme disease in Canada.
AB  - In North America, Lyme disease (LD) is a tick-borne zoonosis caused by the
      spirochete bacterium Borrelia burgdorferi sensu stricto, which is maintained by
      wildlife. Tick vectors and bacteria are currently spreading into Canada and
      causing increasing numbers of cases of LD in humans and raising a pressing need
      for public health responses. There is no vaccine, and LD prevention depends on
      knowing who is at risk and informing them how to protect themselves from
      infection. Recently, it was found in the United States that some strains of B.
      burgdorferi sensu stricto cause severe disease, whereas others cause mild, self
      limiting disease. While many strains occurring in the United States also occur in
      Canada, strains in some parts of Canada are different from those in the United
      States. We therefore recognize a need to identify which strains specific to
      Canada can cause severe disease and to characterize their geographic distribution
      to determine which Canadians are particularly at risk. In this review, we
      summarize the history of emergence of LD in North America, our current knowledge
      of B. burgdorferi sensu stricto diversity, its intriguing origins in the ecology
      and evolution of the bacterium, and its importance for the epidemiology and
      clinical and laboratory diagnosis of LD. We propose methods for investigating
      associations between B. burgdorferi sensu stricto diversity, ecology, and
      pathogenicity and for developing predictive tools to guide public health
      interventions. We also highlight the emergence of B. burgdorferi sensu stricto in
      Canada as a unique opportunity for exploring the evolutionary aspects of tick
      borne pathogen emergence. 

PMID- 26296724
TI  - Pseudomonas aeruginosa and Achromobacter sp. clonal selection leads to successive
      waves of contamination of water in dental care units.
AB  - Dental care unit waterlines (DCUWs) consist of complex networks of thin tubes
      that facilitate the formation of microbial biofilms. Due to the predilection
      toward a wet environment, strong adhesion, biofilm formation, and resistance to
      biocides, Pseudomonas aeruginosa, a major human opportunistic pathogen, is
      adapted to DCUW colonization. Other nonfermentative Gram-negative bacilli, such
      as members of the genus Achromobacter, are emerging pathogens found in water
      networks. We reported the 6.5-year dynamics of bacterial contamination of
      waterlines in a dental health care center with 61 dental care units (DCUs)
      connected to the same water supply system. The conditions allowed the selection
      and the emergence of clones of Achromobacter sp. and P. aeruginosa characterized
      by multilocus sequence typing, multiplex repetitive elements-based PCR, and
      restriction fragment length polymorphism in pulsed-field gel electrophoresis,
      biofilm formation, and antimicrobial susceptibility. One clone of P. aeruginosa
      and 2 clones of Achromobacter sp. colonized successively all of the DCUWs: the
      last colonization by P. aeruginosa ST309 led to the closing of the dental care
      center. Successive dominance of species and clones was linked to biocide
      treatments. Achromobacter strains were weak biofilm producers compared to P.
      aeruginosa ST309, but the coculture of P. aeruginosa and Achromobacter enhanced
      P. aeruginosa ST309 biofilm formation. Intraclonal genomic microevolution was
      observed in the isolates of P. aeruginosa ST309 collected chronologically and in
      Achromobacter sp. clone A. The contamination control was achieved by a complete
      reorganization of the dental health care center by removing the connecting tubes
      between DCUs. 

PMID- 26296725
TI  - Experimental evolution of enhanced growth by Bacillus subtilis at low atmospheric
      pressure: genomic changes revealed by whole-genome sequencing.
AB  - Knowledge of how microorganisms respond and adapt to low-pressure (LP)
      environments is limited. Previously, Bacillus subtilis strain WN624 was grown at
      the near-inhibitory LP of 5 kPa for 1,000 generations and strain WN1106, which
      exhibited increased relative fitness at 5 kPa, was isolated. Genomic sequence
      differences between ancestral strain WN624 and LP-evolved strain WN1106 were
      identified using whole-genome sequencing. LP-evolved strain WN1106 carried amino
      acid-altering mutations in the coding sequences of only seven genes (fliI, parC,
      ytoI, bacD, resD, walK, and yvlD) and a single 9-nucleotide in-frame deletion in
      the rnjB gene that encodes RNase J2, a component of the RNA degradosome. By using
      a collection of frozen stocks of the LP-evolved culture taken at 50-generation
      intervals, it was determined that (i) the fitness increase at LP occurred
      rapidly, while (ii) mutation acquisition exhibited complex kinetics. A knockout
      mutant of rnjB was shown to increase the competitive fitness of B. subtilis at
      both LP and standard atmospheric pressure. 

PMID- 26296727
TI  - Light-dependent sulfide oxidation in the anoxic zone of the Chesapeake Bay can be
      explained by small populations of phototrophic bacteria.
AB  - Microbial sulfide oxidation in aquatic environments is an important ecosystem
      process, as sulfide is potently toxic to aerobic organisms. Sulfide oxidation in
      anoxic waters can prevent the efflux of sulfide to aerobic water masses, thus
      mitigating toxicity. The contribution of phototrophic sulfide-oxidizing bacteria
      to anaerobic sulfide oxidation in the Chesapeake Bay and the redox chemistry of
      the stratified water column were investigated in the summers of 2011 to 2014. In
      2011 and 2013, phototrophic sulfide-oxidizing bacteria closely related to
      Prosthecochloris species of the phylum Chlorobi were cultivated from waters
      sampled at and below the oxic-anoxic interface, where measured light penetration
      was sufficient to support populations of low-light-adapted photosynthetic
      bacteria. In 2012, 2013, and 2014, light-dependent sulfide loss was observed in
      freshly collected water column samples. In these samples, extremely low light
      levels caused 2- to 10-fold increases in the sulfide uptake rate over the sulfide
      uptake rate under dark conditions. An enrichment, CB11, dominated by
      Prosthecochloris species, oxidized sulfide with a Ks value of 11 MUM and a Vmax
      value of 51 MUM min(-1) (mg protein(-1)). Using these kinetic values with in situ
      sulfide concentrations and light fluxes, we calculated that a small population of
      Chlorobi similar to those in enrichment CB11 can account for the observed
      anaerobic light-dependent sulfide consumption activity in natural water samples.
      We conclude that Chlorobi play a far larger role in the Chesapeake Bay than
      currently appreciated. This result has potential implications for coastal anoxic
      waters and expanding oxygen-minimum zones as they begin to impinge on the photic
      zone. 

PMID- 26296726
TI  - FleQ coordinates flagellum-dependent and -independent motilities in Pseudomonas
      syringae pv. tomato DC3000.
AB  - Motility plays an essential role in bacterial fitness and colonization in the
      plant environment, since it favors nutrient acquisition and avoidance of toxic
      substances, successful competition with other microorganisms, the ability to
      locate the preferred hosts, access to optimal sites within them, and dispersal in
      the environment during the course of transmission. In this work, we have observed
      that the mutation of the flagellar master regulatory gene, fleQ, alters bacterial
      surface motility and biosurfactant production, uncovering a new type of motility
      for Pseudomonas syringae pv. tomato DC3000 on semisolid surfaces. We present
      evidence that P. syringae pv. tomato DC3000 moves over semisolid surfaces by
      using at least two different types of motility, namely, swarming, which depends
      on the presence of flagella and syringafactin, a biosurfactant produced by this
      strain, and a flagellum-independent surface spreading or sliding, which also
      requires syringafactin. We also show that FleQ activates flagellum synthesis and
      negatively regulates syringafactin production in P. syringae pv. tomato DC3000.
      Finally, it was surprising to observe that mutants lacking flagella or
      syringafactin were as virulent as the wild type, and only the simultaneous loss
      of both flagella and syringafactin impairs the ability of P. syringae pv. tomato
      DC3000 to colonize tomato host plants and cause disease. 

PMID- 26296728
TI  - Housefly Larva Vermicomposting Efficiently Attenuates Antibiotic Resistance Genes
      in Swine Manure, with Concomitant Bacterial Population Changes.
AB  - Manure from swine treated with antimicrobials as feed additives is a major source
      for the expansion of the antibiotic resistance gene (ARG) reservoir in the
      environment. Vermicomposting via housefly larvae (Musca domestica) can be
      efficiently used to treat manure and regenerate biofertilizer, but few studies
      have investigated its effect on ARG attenuation. Here, we tracked the abundances
      of 9 ARGs and the composition and structure of the bacterial communities in
      manure samples across 6 days of full-scale manure vermicomposting. On day 6, the
      abundances of genes encoding tetracycline resistance [tet(M), tet(O), tet(Q), and
      tet(W)] were reduced (P < 0.05), while those of genes encoding sulfonamide
      resistance (sul1 and sul2) were increased (P < 0.05) when normalized to 16S rRNA.
      The abundances of tetracycline resistance genes were correlated (P < 0.05) with
      the changing concentrations of tetracyclines in the manure. The overall diversity
      and richness of the bacteria significantly decreased during vermicomposting,
      accompanied by a 100 times increase in the relative abundance of
      Flavobacteriaceae spp. Variations in the abundances of ARGs were correlated with
      the changing microbial community structure and the relative abundances of the
      family Ruminococcaceae, class Bacilli, or phylum Proteobacteria. Vermicomposting,
      as a waste management practice, can reduce the overall abundance of ARGs. More
      research is warranted to assess the use of this waste management practice as a
      measure to attenuate the dissemination of antimicrobial residues and ARGs from
      livestock production before vermicompost can be safely used as biofertilizer in
      agroecosystems. 

PMID- 26296729
TI  - Stability of Secondary and Tertiary Structures of Virus-Like Particles
      Representing Noroviruses: Effects of pH, Ionic Strength, and Temperature and
      Implications for Adhesion to Surfaces.
AB  - Loss of ordered molecular structure in proteins is known to increase their
      adhesion to surfaces. The aim of this work was to study the stability of
      norovirus secondary and tertiary structures and its implications for viral
      adhesion to fresh foods and agrifood surfaces. The pH, ionic strength, and
      temperature conditions studied correspond to those prevalent in the principal
      vehicles of viral transmission (vomit and feces) and in the food processing and
      handling environment (pasteurization and refrigeration). The structures of virus
      like particles representing GI.1, GII.4, and feline calicivirus (FCV) were
      studied using circular dichroism and intrinsic UV fluorescence. The particles
      were remarkably stable under most of the conditions. However, heating to 65
      degrees C caused losses of beta-strand structure, notably in GI.1 and FCV, while
      at 75 degrees C the alpha-helix content of GII.4 and FCV decreased and tertiary
      structures unfolded in all three cases. Combining temperature with pH or ionic
      strength caused variable losses of structure depending on the particle type.
      Regardless of pH, heating to pasteurization temperatures or higher would be
      required to increase GII.4 and FCV adhesion, while either low or high
      temperatures would favor GI.1 adhesion. Regardless of temperature, increased
      ionic strength would increase GII.4 adhesion but would decrease GI.1 adhesion.
      FCV adsorption would be greater at refrigeration, pasteurization, or high
      temperature combined with a low salt concentration or at a higher NaCl
      concentration regardless of temperature. Norovirus adhesion mediated by
      hydrophobic interaction may depend on hydrophobic residues normally exposed on
      the capsid surface at pH 3, pH 8, physiological ionic strength, and low
      temperature, while at pasteurization temperatures it may rely more on buried
      hydrophobic residues exposed upon structural rearrangement. 

PMID- 26296730
TI  - Cerium regulates expression of alternative methanol dehydrogenases in
      Methylosinus trichosporium OB3b.
AB  - Methanotrophs have multiple methane monooxygenases that are well known to be
      regulated by copper, i.e., a "copper switch." At low copper/biomass ratios the
      soluble methane monooxygenase (sMMO) is expressed while expression and activity
      of the particulate methane monooxygenase (pMMO) increases with increasing
      availability of copper. In many methanotrophs there are also multiple methanol
      dehydrogenases (MeDHs), one based on Mxa and another based on Xox. Mxa-MeDH is
      known to have calcium in its active site, while Xox-MeDHs have been shown to have
      rare earth elements in their active site. We show here that the expression levels
      of Mxa-MeDH and Xox-MeDH in Methylosinus trichosporium OB3b significantly
      decreased and increased, respectively, when grown in the presence of cerium but
      the absence of copper compared to the absence of both metals. Expression of sMMO
      and pMMO was not affected. In the presence of copper, the effect of cerium on
      gene expression was less significant, i.e., expression of Mxa-MeDH in the
      presence of copper and cerium was slightly lower than in the presence of copper
      alone, but Xox-MeDH was again found to increase significantly. As expected, the
      addition of copper caused sMMO and pMMO expression levels to significantly
      decrease and increase, respectively, but the simultaneous addition of cerium had
      no discernible effect on MMO expression. As a result, it appears Mxa-MeDH can be
      uncoupled from methane oxidation by sMMO in M. trichosporium OB3b but not from
      pMMO. 

PMID- 26296732
TI  - Novel LinA type 3 delta-hexachlorocyclohexane dehydrochlorinase.
AB  - LinA is the first enzyme of the microbial degradation pathway of a chlorinated
      insecticide, hexachlorocyclohexane (HCH), and mediates the dehydrochlorination of
      alpha-, gamma-, and delta-HCH. Its two variants, LinA type 1 and LinA type 2,
      which differ at 10 out of 156 amino acid residues, have been described. Their
      activities for the metabolism of different HCH isomers differ considerably but
      overall are high for gamma-HCH, moderate for alpha-HCH, low for delta-HCH, and
      lacking for beta-HCH. Here, we describe the characterization of a new variant of
      this enzyme, LinA type 3, whose gene was identified from the metagenome of an HCH
      contaminated soil sample. Its deduced primary structure in the region spanning
      amino acid residues 1 to 147 of the protein exhibits 17 and 12 differences from
      LinA type 1 and LinA type 2, respectively. In addition, the residues GIHFAPS,
      present at the region spanning residues 148 to 154 in both LinA type 1 and LinA
      type 2, are deleted in LinA type 3.The activity of LinA type 3 for the metabolism
      of delta-HCH is several orders of magnitude higher than that of LinA type 1 or
      LinA type 2 and can be useful for improvement of the metabolism of delta-HCH. 

PMID- 26296731
TI  - Quantitative microbial ecology through stable isotope probing.
AB  - Bacteria grow and transform elements at different rates, and as yet, quantifying
      this variation in the environment is difficult. Determining isotope enrichment
      with fine taxonomic resolution after exposure to isotope tracers could help, but
      there are few suitable techniques. We propose a modification to stable isotope
      probing (SIP) that enables the isotopic composition of DNA from individual
      bacterial taxa after exposure to isotope tracers to be determined. In our
      modification, after isopycnic centrifugation, DNA is collected in multiple
      density fractions, and each fraction is sequenced separately. Taxon-specific
      density curves are produced for labeled and nonlabeled treatments, from which the
      shift in density for each individual taxon in response to isotope labeling is
      calculated. Expressing each taxon's density shift relative to that taxon's
      density measured without isotope enrichment accounts for the influence of nucleic
      acid composition on density and isolates the influence of isotope tracer
      assimilation. The shift in density translates quantitatively to isotopic
      enrichment. Because this revision to SIP allows quantitative measurements of
      isotope enrichment, we propose to call it quantitative stable isotope probing
      (qSIP). We demonstrated qSIP using soil incubations, in which soil bacteria
      exhibited strong taxonomic variations in (18)O and (13)C composition after
      exposure to [(18)O]water or [(13)C]glucose. The addition of glucose increased the
      assimilation of (18)O into DNA from [(18)O]water. However, the increase in (18)O
      assimilation was greater than expected based on utilization of glucose-derived
      carbon alone, because the addition of glucose indirectly stimulated bacteria to
      utilize other substrates for growth. This example illustrates the benefit of a
      quantitative approach to stable isotope probing. 

PMID- 26296733
TI  - Mucosa-associated Faecalibacterium prausnitzii phylotype richness is reduced in
      patients with inflammatory bowel disease.
AB  - Faecalibacterium prausnitzii depletion in intestinal diseases has been
      extensively reported, but little is known about intraspecies variability. This
      work aims to determine if subjects with gastrointestinal disease host mucosa
      associated F. prausnitzii populations different from those hosted by healthy
      individuals. A new species-specific PCR-denaturing gradient gel electrophoresis
      (PCR-DGGE) method targeting the 16S rRNA gene was developed to fingerprint F.
      prausnitzii populations in biopsy specimens from 31 healthy control (H) subjects
      and 36 Crohn's disease (CD), 23 ulcerative colitis (UC), 6 irritable bowel
      syndrome (IBS), and 22 colorectal cancer (CRC) patients. The richness of F.
      prausnitzii subtypes was lower in inflammatory bowel disease (IBD) patients than
      in H subjects. The most prevalent operational taxonomic units (OTUs) consisted of
      four phylotypes (OTUs with a 99% 16S rRNA gene sequence similarity [OTU99]),
      which were shared by all groups of patients. Their distribution and the presence
      of some disease-specific F. prausnitzii phylotypes allowed us to differentiate
      the populations in IBD and CRC patients from that in H subjects. At the level of
      a minimum similarity of 97% (OTU97), two phylogroups accounted for 98% of the
      sequences. Phylogroup I was found in 87% of H subjects but in under 50% of IBD
      patients (P = 0.003). In contrast, phylogroup II was detected in >75% of IBD
      patients and in only 52% of H subjects (P = 0.005). This study reveals that even
      though the main members of the F. prausnitzii population are present in both H
      subjects and individuals with gut diseases, richness is reduced in the latter and
      an altered phylotype distribution exists between diseases. This approach may
      serve as a basis for addressing the suitability of F. prausnitzii phylotypes to
      be quantified as a putative biomarker of disease and depicting the importance of
      the loss of these subtypes in disease pathogenesis. 

PMID- 26296735
TI  - ADAM10 mediates the house dust mite-induced release of chemokine ligand CCL20 by
      airway epithelium.
AB  - BACKGROUND: House dust mite (HDM) acts on the airway epithelium to induce airway
      inflammation in asthma. We previously showed that the ability of HDM to induce
      allergic sensitization in mice is related to airway epithelial CCL20 secretion.
      OBJECTIVE: As a disintegrin and metalloprotease (ADAM)s have been implicated in
      chemokine shedding, we sought to determine their involvement in HDM-induced
      release of chemokines, including CCL20, by airway epithelial cells. METHODS: We
      studied the effects of pharmacological ADAM inhibitors as well as ADAM10 and
      ADAM17 siRNA downregulation on chemokine release using (multiplex) ELISA in
      supernatants from HDM-exposed human bronchial epithelial 16HBE cells and primary
      normal human bronchial epithelial cells (NHBE) at 4-24 h. RESULTS: House dust)
      mite markedly increased CCL20 levels in both 16HBE and NHBE cells (16-24 h). In
      16HBE cells, the HDM-induced increase was observed as early as 4 h upon exposure
      and the use of specific inhibitors indicated the involvement of ADAM10/17
      mediated shedding. siRNA knockdown of ADAM10, but not of ADAM17, significantly
      reduced the HDM-induced release of CCL20 in both 16HBE and NHBE cells. A similar
      effect was observed for HDM-induced CCL2, CCL5, and CXCL8 release in NHBE cells.
      The HDM-induced increase in CCL20 levels was not affected by protein synthesis
      inhibitor cycloheximide nor protein transport inhibitor monensin, indicating that
      HDM induces surface shedding of chemokines. CONCLUSION: Our data show for the
      first time that ADAM10 activity contributes to HDM-induced shedding of
      chemokines, including CCL20. The ADAM10/CCL20 axis may be a target for novel
      therapeutic strategies in asthma.

PMID- 26296736
TI  - Endovascular Embolization of Visceral Artery Pseudoaneurysms Using Modified
      Injection Technique with N-Butyl Cyanoacrylate Glue.
AB  - PURPOSE: To evaluate the indications, feasibility, safety, and effectiveness of N
      butyl cyanoacrylate (NBCA) with modified injection technique in embolization of
      visceral artery pseudoaneurysms (PSAs). MATERIALS AND METHODS: A retrospective
      evaluation was performed of 31 patients (26 men, 5 women; mean age, 32.6 y) with
      visceral artery PSAs that were treated with embolization using NBCA with modified
      sequential injection and flushing technique. The most common indication for using
      NBCA was preservation of a major feeding artery (n = 18), followed by difficult
      catheterization secondary to arterial tortuosity (n = 5), failed previous coil
      embolization (n = 4), and short landing zone for coils (n = 4). NBCA alone was
      used in 25 patients, and NBCA with coils was used in 6 patients. The patients
      were followed clinically until discharge and 1 and 3 months after discharge.
      RESULTS: The mean amount of NBCA-ethiodized oil (Lipiodol; Guerbet LLC,
      Villepinte, France) mixture injected was 0.24 mL (range, 0.1-1.1 mL).
      Embolization with NBCA was technically successful in all (100%) patients.
      Recurrence was seen in 3 (9.7%; 2--splenic artery; 1--left gastric artery)
      patients after a mean time of 16.3 days (range, 10-27 d) of initial embolization
      resulting in clinical success of 90.3%. All 3 patients underwent successful
      repeat embolization with secondary technical success rate of 100%. Minor (pain)
      and major (nontarget embolization in 2; microcatheter adhesion and fracture in 1)
      complications were seen in 3 patients each. CONCLUSIONS: NBCA is a safe and
      effective embolization agent when injected with modified technique in treatment
      of visceral artery PSAs.

PMID- 26296737
TI  - Imaging Predictors of Elevated Lung Shunt Fraction in Patients Being Considered
      for Yttrium-90 Radioembolization.
AB  - PURPOSE: To identify imaging findings associated with elevated lung shunt
      fraction (LSF) in patients being considered for yttrium-90 ((90)Y)
      radioembolization. MATERIALS AND METHODS: During the period 2009-2014, 152
      consecutive patients underwent planning hepatic arteriography with technetium-99m
      ((99m)Tc) macroaggregated albumin (MAA) injection. Computed tomography (CT) or
      magnetic resonance imaging performed before the procedure for each patient was
      assessed for hepatic vein (HV) tumor thrombus or occlusion from external
      compression by tumor. When imaging was a multiphase CT scan (117 patients), the
      arterial phase was evaluated for evidence of early HV opacification (relative to
      unaffected HVs), indicating hepatic venous shunting. These factors were
      correlated with LSF determined by (99m)Tc-MAA imaging. RESULTS: Median LSF was
      6.7% (range, < 0.1%-71%), significantly higher for HCC (8.0% vs 6.3% for other
      tumors, P = .048). Larger tumor size was associated with higher LSF in univariate
      analysis (P = .001). There was high interobserver agreement for determining
      hepatic venous shunting (97%, kappa = 0.847), which was associated with higher
      LSF (P < .001; 78% sensitivity, 93% specificity). Of 5 cases of HV tumor
      thrombus, all had high (> 20%) LSF (P < .001). HV occlusion was also associated
      with higher LSF (P = .039). Multivariate analysis confirmed that early HV
      opacification and either HV tumor thrombus or occlusion were associated with
      higher LSF. CONCLUSIONS: Early HV opacification and HV tumor thrombus or
      occlusion on cross-sectional imaging performed before radioembolization are
      associated with elevated LSF, which may contraindicate or limit the dose
      delivered in (90)Y radioembolization. This information could be helpful during
      patient counseling for anticipating the most appropriate mode of liver-directed
      therapy.

PMID- 26296739
TI  - Integrative Indicator for Assessing the Alert Levels of Algal Bloom in Lakes:
      Lake Taihu as a Case Study.
AB  - Algal blooms have recently become one of the most serious environmental problems
      in eutrophic freshwater ecosystems worldwide. Although many observation and
      simulation approaches have been applied to predict algal blooms, few studies have
      addressed the alert levels of algal blooms using integrative indicators in a
      large lake with multiple service function and significant horizontal
      heterogeneity. This study developed an integrative indicator assessment system
      (IIAS) to rank the alert level of algal blooms. In the IIAS, algal biomass, area
      percentage, distance from drinking water intake points, distance from scenic
      zones and duration of algal bloom were used as indicators to calculate a
      comprehensive alert level, which was classified into five grades (Vigilance, Low,
      Moderate, High, and Severe). Lake Taihu was taken as a case study to assess the
      comprehensive alert level of algal blooms in 2007 and 2010. The comprehensive
      alert level showed obvious spatial-temporal patterns, with an acceptable accuracy
      in Lake Taihu. The comprehensive alert levels were relatively higher in typical
      phytoplankton subzones than typical hydrophytes subzones and are more sensitive
      to weight factor in the northern and western subzones where high biomass usually
      occurs. Case study showed a very good application of the proposed comprehensive
      alert level assessment methodology, which can be adjusted to predict the degree
      of hazard of algal blooms in multi-service function large lakes to help the
      government and decision makers to act to prevent the disaster from algal bloom
      spreading. 

PMID- 26296738
TI  - Genetically Modified Herbicide-Tolerant Crops, Weeds, and Herbicides: Overview
      and Impact.
AB  - Genetically modified (GM) crops have been and continue to be a subject of
      controversy despite their rapid adoption by farmers where approved. For the last
      two decades, an important matter of debate has been their impact on pesticide
      use, particularly for herbicide-tolerant (HT) crops. Some claim that these crops
      bring about a decrease in herbicide use, while others claim the opposite. In
      fact, since 1996, most cultivated GMOs have been GMHT crops, which involve the
      use of an associated herbicide, generally glyphosate. In their very first years
      of adoption, HT crops often led to some decrease in herbicide use. However, the
      repetition of glyphosate-tolerant crops and of glyphosate only applications in
      the same fields without sufficient alternation and herbicide diversity has
      contributed to the appearance of glyphosate-resistant weeds. These weeds have
      resulted in a rise in the use of glyphosate and other herbicides. This article
      explores this situation and the impacts of herbicide-resistant weeds, using an
      interdisciplinary approach and drawing on recent data. The paper analyzes the
      spread of GMHT crops worldwide and their consequences on herbicide use in the USA
      in particular. It then addresses the global development of glyphosate-resistant
      weeds and their impact, particularly focusing on the USA. Finally, the last
      section explores how industry, farmers, and weed scientists are coping with the
      spread of resistant weeds. The concluding comments deal more widely with trends
      in GM crops. 

PMID- 26296740
TI  - Association Between Substance Use and the Perpetration of Family Violence in
      Industrialized Countries: A Systematic Review.
AB  - This review examines the association between alcohol and illicit drug use and the
      perpetration of intimate partner violence (IPV) and child maltreatment (CM). In
      clinical populations, alcohol use is related to IPV, although other variables are
      also known to influence this relationship. Studies in specialized social/health
      care and in the community have also demonstrated the association between alcohol
      use and IPV. Although data on the association between illicit drug use and IPV
      are less clear, in most studies perpetration seems related to the use of cannabis
      and cocaine. The occurrence of CM is related to alcohol use in specialized
      social/health care and community populations but has not been extensively
      investigated in clinical samples. These findings also apply to studies on the
      association between illicit drug use and CM. Moreover, many studies on CM fail to
      distinguish between the effects of alcohol and those of illicit drugs. This
      review concludes with recommendations for future research about substance use and
      family violence and discusses implications for prevention and treatment.

PMID- 26296734
TI  - The ocean as a global reservoir of antibiotic resistance genes.
AB  - Recent studies of natural environments have revealed vast genetic reservoirs of
      antibiotic resistance (AR) genes. Soil bacteria and human pathogens share AR
      genes, and AR genes have been discovered in a variety of habitats. However, there
      is little knowledge about the presence and diversity of AR genes in marine
      environments and which organisms host AR genes. To address this, we identified
      the diversity of genes conferring resistance to ampicillin, tetracycline,
      nitrofurantoin, and sulfadimethoxine in diverse marine environments using
      functional metagenomics (the cloning and screening of random DNA fragments).
      Marine environments were host to a diversity of AR-conferring genes. Antibiotic
      resistant clones were found at all sites, with 28% of the genes identified as
      known AR genes (encoding beta-lactamases, bicyclomycin resistance pumps, etc.).
      However, the majority of AR genes were not previously classified as such but had
      products similar to proteins such as transport pumps, oxidoreductases, and
      hydrolases. Furthermore, 44% of the genes conferring antibiotic resistance were
      found in abundant marine taxa (e.g., Pelagibacter, Prochlorococcus, and Vibrio).
      Therefore, we uncovered a previously unknown diversity of genes that conferred an
      AR phenotype among marine environments, which makes the ocean a global reservoir
      of both clinically relevant and potentially novel AR genes. 

PMID- 26296741
TI  - Industrial maxillofacial injuries in the United Kingdom.
AB  - The treatment of maxillofacial injuries forms a substantial part of the work in
      oral and maxillofacial units, but injuries sustained in work-related incidents
      are uncommon, mainly because of the strict enforcement of Health and Safety
      policies. We used data from the Health and Safety Executive in the United Kingdom
      to review the incidence and aetiology of maxillofacial injuries that result from
      industrial accidents in the UK, and highlight the case of a worker who sustained
      an isolated fracture of the nasoethmoidal complex when he was trapped in a cheese
      press. In 2010-2011, roughly 115,379 accidents or incidents at work were reported
      in the UK, and of the 1623 (1%) that were maxillofacial, 81% occurred in the
      service sector. The most common mechanism of injury was assault (37%) and the
      most common injury was contusion (30%). Since the introduction of the Health and
      Safety Act, work-related accidents in the UK have decreased considerably.
      However, they will continue to occur because of human error.

PMID- 26296742
TI  - Blocking rpS6 Phosphorylation Exacerbates Tsc1 Deletion-Induced Kidney Growth.
AB  - The molecular mechanisms underlying renal growth and renal growth-induced nephron
      damage remain poorly understood. Here, we report that in murine models, deletion
      of the tuberous sclerosis complex protein 1 (Tsc1) in renal proximal tubules
      induced strikingly enlarged kidneys, with minimal cystogenesis and occasional
      microscopic tumorigenesis. Signaling studies revealed hyperphosphorylation of
      eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and
      increased phosphorylation of ribosomal protein S6 (rpS6) in activated renal
      tubules. Notably, knockin of a nonphosphorylatable rpS6 in these Tsc1-mutant mice
      exacerbated cystogenesis and caused drastic nephron damage and renal fibrosis,
      leading to kidney failure and a premature death rate of 67% by 9 weeks of age. In
      contrast, Tsc1 single-mutant mice were all alive and had far fewer renal cysts at
      this age. Mechanistic studies revealed persistent activation of mammalian target
      of rapamycin complex 1 (mTORC1) signaling causing hyperphosphorylation and
      consequent accumulation of 4E-BP1, along with greater cell proliferation, in the
      renal tubules of Tsc1 and rpS6 double-mutant mice. Furthermore, pharmacologic
      treatment of Tsc1 single-mutant mice with rapamycin reduced hyperphosphorylation
      and accumulation of 4E-BP1 but also inhibited phosphorylation of rpS6. Rapamycin
      also exacerbated cystic and fibrotic lesions and impaired kidney function in
      these mice, consequently leading to a premature death rate of 40% within 2 weeks
      of treatment, despite destroying tumors and decreasing kidney size. These
      findings indicate that Tsc1 prevents aberrant renal growth and tumorigenesis by
      inhibiting mTORC1 signaling, whereas phosphorylated rpS6 suppresses cystogenesis
      and fibrosis in Tsc1-deleted kidneys.

PMID- 26296743
TI  - Chloroquine sensitivity: diminished prevalence of chloroquine-resistant gene
      marker pfcrt-76 13 years after cessation of chloroquine use in Msambweni, Kenya.
AB  - BACKGROUND: Plasmodium falciparum resistance to chloroquine (CQ) denied
      healthcare providers access to a cheap and effective anti-malarial drug.
      Resistance has been proven to be due to point mutations on the parasite's pfcrt
      gene, particularly on codon 76, resulting in an amino acid change from lysine to
      threonine. This study sought to determine the prevalence of the pfcrt K76T
      mutation 13 years after CQ cessation in Msambweni, Kenya. METHODS: Finger-prick
      whole blood was collected on 3MM Whatman((r)) filter paper from 99 falciparum
      malaria patients. Parasite DNA was extracted via the Chelex method from
      individual blood spots and used as template in nested PCR amplification of pfcrt.
      Apo1 restriction enzyme was used to digest the amplified DNA to identify the
      samples as wild type or sensitive at codon 76. Prevalence figures of the mutant
      pfcrt 76T gene were calculated by dividing the number of samples bearing the
      mutant gene with the total number of samples multiplied by 100 %. Chi square
      tests were used to test the significance of the findings against previous
      prevalence figures. RESULTS: Out of 99 clinical samples collected in 2013,
      prevalence of the mutant pfcrt 76T gene stood at 41 %. CONCLUSION: The results
      indicate a significant [chi(2) test, P <= 0.05 (2006 vs 2013)] reversal to
      sensitivity by the P. falciparum population in the study site compared to the
      situation reported in 2006 at the same study site. This could primarily be driven
      by diminished use of CQ in the study area in line with the official policy.
      Studies to establish prevalence of the pfcrt 76T gene could be expanded
      countrywide to establish the CQ sensitivity status and predict a date when CQ may
      be re-introduced as part of malaria chemotherapy.

PMID- 26296744
TI  - Diversity of exophillic acid derivatives in strains of an endophytic Exophiala
      sp.
AB  - Members of the fungal genus Exophiala are common saprobes in soil and water
      environments, opportunistic pathogens of animals, or endophytes in plant roots.
      Their ecological versatility could imply a capacity to produce diverse secondary
      metabolites, but only a few studies have aimed at characterizing their chemical
      profiles. Here, we assessed the secondary metabolites produced by five Exophiala
      sp. strains of a particular phylotype, isolated from roots of Microthlaspi
      perfoliatum growing in different European localities. Exophillic acid and two
      previously undescribed compounds were isolated from these strains, and their
      structures were elucidated by spectroscopic methods using MS, 1D and 2D NMR.
      Bioassays revealed a weak activity of these compounds against disease-causing
      protozoa and mammalian cells. In addition, 18 related structures were identified
      by UPLC/MS based on comparisons with the isolated structures. Three Exophiala
      strains produced derivatives containing a beta-d-glucopyranoside moiety, and
      their colony morphology was distinct from the other two strains, which produced
      derivatives lacking beta-d-glucopyranoside. Whether the chemical/morphological
      strain types represent variants of the same genotype or independent genetic
      populations within Exophiala remains to be evaluated. 

PMID- 26296745
TI  - Rickenyls A-E, antioxidative terphenyls from the fungus Hypoxylon rickii
      (Xylariaceae, Ascomycota).
AB  - Our screening efforts for new natural products with interesting bioactivity have
      revealed the neotropical ascomycete Hypoxylon rickii as a prolific source. We
      isolated five secondary metabolites with a p-terphenyl backbone from the mycelial
      extract of a fermentation of this fungus in 70 l scale by using RP-HPLC, which
      were named rickenyls A-E (1-5). Their structures were elucidated by X-ray
      crystallography and NMR spectroscopy, complemented by HRESIMS. Two of the
      compounds contained a quinone core structure in ortho (2) and para-position (5),
      respectively. We obtained 2 spontaneously and by lead tetraacetate oxidation from
      1. All compounds were screened for antimicrobial, antioxidative and cytotoxic
      activities. Rickenyl A (1) exhibited strong antioxidative effects and moderate
      cytotoxic activity against various cancer cell lines.

PMID- 26296746
TI  - The effects of mineral nitrogen limitation, competition, arbuscular mycorrhiza,
      and their respective interactions, on morphological and chemical plant traits of
      Plantago lanceolata.
AB  - Plants are sessile organisms that suffer from a multitude of challenges such as
      abiotic stress or the interactions with competitors, antagonists and symbionts,
      which influence their performance as well as their eco-physiological and
      biochemical responses in complex ways. In particular, the combination of
      different stressors and their impact on plant biomass production and the plant's
      ability to metabolically adjust to these challenges are less well understood. To
      study the effects of mineral nitrogen (N) availability, interspecific competition
      and the association with arbuscular mycorrhizal fungi (AMF) on biomass
      production, biomass allocation patterns (root/shoot ratio, specific leaf area)
      and metabolic responses, we chose the model organism Plantago lanceolata L.
      (Plantaginaceae). Plants were grown in a full factorial experiment. Biomass
      production and its allocation patterns were assessed at harvest, and the
      influence of the different treatments and their interactions on the plant
      metabolome were analysed using a metabolic fingerprinting approach with ultra
      high performance liquid chromatography coupled with time-of-flight-mass
      spectrometry. Limited supply of mineral N caused the most pronounced changes with
      respect to plant biomass and biomass allocation patterns, and altered the
      concentrations of more than one third of the polar plant metabolome. Competition
      also impaired plant biomass production, yet affected the plant metabolome to a
      much lesser extent than limited mineral N supply. The interaction of competition
      and limited mineral N supply often caused additive changes on several traits. The
      association with AMF did not enhance biomass production, but altered biomass
      allocation patterns such as the root/shoot ratio and the specific leaf area.
      Interestingly, we did not find significant changes in the plant metabolome caused
      by AMF. A targeted analysis revealed that only limited mineral N supply reduced
      the concentrations of one of the main target defence compounds of P. lanceolata,
      the iridoid glycoside catalpol. In general, the interaction of competition and
      limited mineral N supply led to additive changes, while the association with AMF
      in any case alleviated the observed stress responses. Our results show that the
      joint analysis of biomass/allocation patterns and metabolic traits allows a more
      comprehensive interpretation of plant responses to different biotic and abiotic
      challenges; specifically, when multiple stresses interact. 

PMID- 26296748
TI  - Mathematical modeling of receptor occupancy data: A valuable technology for
      biotherapeutic drug development.
AB  - BACKGROUND: In drug development, in vivo assessment of target engagement provides
      confidence when testing the drug's mechanism of action and improves the
      likelihood of clinical success. For biologics, receptor occupancy (RO) determined
      from circulating cells can provide evidence of target engagement. Integrating
      this information with mathematical modeling can further enhance the understanding
      of drug-target interactions and the biological factors that are critical to the
      successful modulation of the target and ultimately the disease state. METHODS:
      This mini-review presents two specific types of mathematical models used to
      describe antibody-receptor systems and highlights how experimental data can
      inform the model parameters. Simulations are used to illustrate how various
      mechanisms influence RO, PK and total cellular receptor profiles. RESULTS: The
      simulations demonstrate the effect antibody-receptor internalization, affinity
      and receptor turnover have on commonly acquired data in drug development.
      CONCLUSIONS: Integrating RO data with mathematical models such as the two
      presented here (target-mediated drug disposition and site-of-action models) can
      provide a more comprehensive view of the biological system, which can be used to
      test hypotheses, extrapolate preclinical findings to humans and impact clinical
      study designs and risk assessments for the successful development of
      biotherapeutics.

PMID- 26296747
TI  - Characterisation of neurons derived from a cortical human neural stem cell line
      CTX0E16.
AB  - INTRODUCTION: Conditionally immortalised human neural progenitor cells (hNPCs)
      represent a robust source of native neural cells to investigate physiological
      mechanisms in both health and disease. However, in order to recognise the utility
      of such cells, it is critical to determine whether they retain characteristics of
      their tissue of origin and generate appropriate neural cell types upon
      differentiation. To this end, we have characterised the conditionally
      immortalised, cortically-derived, human NPC line, CTX0E16, investigating the
      molecular and cellular phenotype of differentiated neurons to determine whether
      they possess characteristics of cortical glutamatergic neurons. METHODS:
      Differentiated CTX0E16 cells were characterised by assessing expression of
      several neural fates markers, and examination of developing neuronal morphology.
      Expression of neurotransmitter receptors, signalling proteins and related
      proteins were assessed by q- and RT-PCR and complemented by Ca(2+) imaging,
      electrophysiology and assessment of ERK signalling in response to
      neurotransmitter ligand application. Finally, differentiated neurons were
      assessed for their ability to form putative synapses and to respond to activity
      dependent stimulation. RESULTS: Differentiation of CTX0E16 hNPCs predominately
      resulted in the generation of neurons expressing markers of cortical and
      glutamatergic (excitatory) fate, and with a typical polarized neuronal
      morphology. Gene expression analysis confirmed an upregulation in the expression
      of cortical, glutamatergic and signalling proteins following differentiation.
      CTX0E16 neurons demonstrated Ca(2+) and ERK1/2 responses following exogenous
      neurotransmitter application, and after 6 weeks displayed spontaneous Ca(2+)
      transients and electrophysiological properties consistent with that of immature
      neurons. Differentiated CTX0E16 neurons also expressed a range of pre- and post
      synaptic proteins that co-localized along distal dendrites, and moreover,
      displayed structural plasticity in response to modulation of neuronal activity.
      CONCLUSIONS: Taken together, these findings demonstrate that the CTX0E16 hNPC
      line is a robust source of cortical neurons, which display functional properties
      consistent with a glutamatergic phenotype. Thus CTX0E16 neurons can be used to
      study cortical cell function, and furthermore, as these neurons express a range
      of disease-associated genes, they represent an ideal platform with which to
      investigate neurodevelopmental mechanisms in native human cells in health and
      disease.

PMID- 26296749
TI  - Artificial Intelligence in Medicine AIME 2013.

PMID- 26296750
TI  - Long-chain omega-3 fatty acids, fibrates and niacin as therapeutic options in the
      treatment of hypertriglyceridemia: a review of the literature.
AB  - Hypertriglyceridemia affects approximately 33% of the US population. Elevated
      triglyceride levels are independently associated with cardiovascular disease
      (CVD) risk, and severe hypertriglyceridemia is a risk factor for acute
      pancreatitis. Guidelines for the management of severe hypertriglyceridemia (>=5.6
      mmol/L [>=500 mg/dL]) recommend immediate use of triglyceride-lowering agents;
      however, statins remain the first line of therapy for the management of mild to
      moderate hypertriglyceridemia (1.7-5.6 mmol/L [150-499 mg/dL]). Statins primarily
      target elevated low-density lipoprotein cholesterol levels, but have also been
      shown to reduce mean triglyceride levels by up to 18% (or 43% in patients with
      triglyceride levels>=3.1 mmol/L [>=273 mg/dL]). However, individuals with
      hypertriglyceridemia may need additional reduction in triglyceride-rich
      lipoproteins and remnant particles to further reduce residual CVD risk. A number
      of guidelines recommend the addition of fibrates, niacin, or long-chain omega-3
      fatty acids if elevated triglyceride or non-high-density lipoprotein cholesterol
      levels persist despite the use of high-intensity statin therapy. This review
      evaluates the impact of fibrates, niacin, and long-chain omega-3 fatty acids on
      lipid profiles and cardiovascular outcomes in patients with hypertriglyceridemia.
      It also assesses the adverse effects and drug-drug interactions associated with
      these triglyceride-lowering agents, because although they have all been shown to
      effectively reduce triglyceride levels in patients with hypertriglyceridemia,
      they differ with regard to their associated benefit-risk profiles. Long-chain
      omega-3 fatty acids may be a well-tolerated and effective alternative to fibrates
      and niacin, yet further large-scale clinical studies are required to evaluate
      their effects on cardiovascular outcomes and CVD risk reduction in patients with
      hypertriglyceridemia.

PMID- 26296751
TI  - Berberine, a natural compound, suppresses Hedgehog signaling pathway activity and
      cancer growth.
AB  - BACKGROUND: Berberine (BBR), a natural alkaloid compound, is used as a non
      prescription drug in China for treating diarrhea and gastroenteritis. Many
      studies have revealed that BBR possesses anticancer effect. However, the
      molecular mechanisms underlying its anticancer action is far from being fully
      elucidated. This study is aimed to determine the effect of BBR on the hedgehog
      (Hh) activity and the growth of cancers addiction to Hh activity. METHODS: The Hh
      activity was determined by dual luciferase assays and quantitative RT-PCR
      analyses. The growth inhibition of BBR on medulloblastoma which was obtained from
      ptch+/-;p53-/- mice was analyzed by 5-bromo-2-deoxyuridine (Brdu) assays and by
      allografting the medulloblastoma into nude mice. The data were statistically
      analyzed by one-way analysis of variance (ANOVA), and multiple comparison between
      the groups was performed using Dunnett's method. RESULTS: In this study, we found
      that BBR significantly inhibited the Hh pathway activity. Meanwhile, we observed
      that BBR failed to affect the transcriptional factors activities provoked by
      tumor necrosis factor-alpha (TNF-alpha) and Prostaglandin E2 (PGE2), thus
      suggesting its unique property against Hh pathway activity. Further studies
      revealed that BBR inhibited the Hh pathway activity by potentially targeting the
      critical component Smoothened (Smo) and most likely shared the same binding site
      on Smo with cyclopamine, a classical Smo inhibitor. Finally, we demonstrated that
      BBR obviously suppressed the Hh-dependent medulloblastoma growth in vitro and in
      vivo. CONCLUSION: Collectively, our study uncovered a novel molecular mechanism
      responsible for the anticancer action of BBR, thus opening the way for the usage
      of BBR for therapeutics of cancers addiction to aberrant Hh pathway activity.

PMID- 26296753
TI  - Dysfunctional meta-cognitive beliefs mediate the relation between temperament
      traits and hallucination-proneness in non-clinical population.
AB  - We investigated whether dysfunctional metacognitive beliefs (negative beliefs
      about uncontrollability and danger of thoughts) mediate the relationship between
      temperamental characteristics of behavior and hallucinatory-like experiences in
      healthy subjects (n=137). Our analyses showed that four temperamental traits
      (emotional reactivity, perseveration, endurance and briskness) were mediated by
      negative beliefs about uncontrollability and danger of thoughts in relation to
      hallucination proneness. Our research tentatively suggests that temperament
      affects hallucination proneness via metacognition. 

PMID- 26296752
TI  - Outcomes of resections for pancreatic adenocarcinoma with suspected venous
      involvement: a single center experience.
AB  - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) patients frequently present
      with borderline resectable disease, which can be due to invasion of the
      portal/superior mesenteric vein (PV/SMV). Here, we analyzed this group of
      patients, with emphasis on short and long-term outcomes. METHODS: 156 patients
      who underwent a resection for PDAC were included in the analysis and sub
      stratified into a cohort of patients with PV/SMV resection (n = 54) versus those
      with standard surgeries (n = 102). RESULTS: While venous resections could be
      performed safely, there was a trend towards shorter median survival in the PV/SMV
      resection group (22.7 vs. 15.8 months, p = 0.157). These tumors were
      significantly larger (3.5 vs. 4.3 cm; p = 0.026) and margin-positivity was more
      frequent (30.4% vs. 44.4%, p = 0.046). CONCLUSION: Venous resection was
      associated with a higher rate of margin positivity and a trend towards shorter
      survival. However, compared to non-surgical treatment, resection offers the best
      chance for long term survival.

PMID- 26296754
TI  - Angiotensin converting enzyme activity is positively associated with IL-17a
      levels in patients with schizophrenia.
AB  - Previous studies of our group showed increased plasmatic Angiotensin-I Converting
      Enzyme (ACE) activity in schizophrenia (SCZ) patients compared to healthy
      controls, which was also associated to poor cognitive functioning. The ACE main
      product angiotensin II (Ang-II) has pro-inflammatory properties. Activated immune
      inflammatory responses in SCZ and their association with disease progression and
      cognitive impairments are also well-described. Therefore, we examined here the
      association of plasma ACE activity and inflammatory mediators in 33 SCZ patients
      and 92 healthy controls. Non-parametric correlations were used to investigate the
      association of the enzyme activity and the peripheral levels of immune
      inflammatory markers as interleukins, tumor necrosis factor (TNF-alpha), and
      interferon (IFN-gamma). Although no significant correlations could be observed
      for ACE activity and measured cytokines levels in healthy controls, a significant
      positive correlation for ACE enzymatic activity and IL-17a levels was observed in
      SCZ patients. Correcting for gender did not change these results. Moreover, a
      significant association for ACE activity and IFN-gamma levels was also observed.
      To our knowledge, this is the first study to show a significant association
      between higher ACE activity and the levels of cytokines, namely IL-17a and IFN
      gamma, in patients with SCZ. 

PMID- 26296756
TI  - Gender differences in the clinical characteristics and psychiatric comorbidity in
      patients with antisocial personality disorder.
AB  - Gender is an important variable in the study of mental health because of the
      actual and perceived differences between men and women. Relatively little is
      known how males and females differ in their manifestations of antisocial
      personality disorder (ASPD). Demographic and clinical features of 323
      participants with ASPD were assessed and recorded. Women had fewer episodes of
      antisocial behavior involving or not involving police, higher scores on the
      Childhood Trauma Questionnaire (CTQ) and on Emotional Abuse and Sexual Abuse
      subscales of the CTQ compared to men. CTQ scores positively correlated with the
      number of episodes of antisocial behavior involving police in men but not in
      women. The percentage of patients with comorbid borderline and histrionic
      personality disorders was higher and the percentage of participants with cocaine
      use disorder was lower among women compared to men. Comorbid alcohol use disorder
      was frequent in both groups, while a higher percentage of women had comorbid mood
      disorders compared to men. Logistic regression analysis demonstrates that CTQ
      scores, histrionic personality disorder, and antisocial behavior involving the
      police drive the difference between the groups. Our findings indicate that
      treatment of individuals with ASPD should focus on the management of comorbid
      psychiatric disorders. 

PMID- 26296755
TI  - Low expression of Gria1 and Grin1 glutamate receptors in the nucleus accumbens of
      Spontaneously Hypertensive Rats (SHR).
AB  - The Spontaneously Hypertensive Rat (SHR) strain is a classical animal model for
      the study of essential hypertension. Recently, our group suggested that this
      strain could be a useful animal model for schizophrenia, which is a severe mental
      illness with involvement of glutamatergic system. The aim of this study is to
      investigate glutamatergic receptors (Gria1 and Grin1) and glycine transporter
      (Glyt1) gene expression in the prefrontal cortex (PFC) and nucleus accumbens
      (NAcc) of SHR animals. The effects in gene expression of a chronic treatment with
      antipsychotic drugs (risperidone, haloperidol and clozapine) were also analyzed.
      Animals were treated daily for 30 days, and euthanized for brain tissue
      collection. The expression pattern was evaluated by Real Time Reverse
      Transcriptase (RT) PCR technique. In comparison to control rats, SHR animals
      present a lower expression of both NMDA (Grin1) and AMPA (Gria1) gene receptors
      in the NAcc. Antipsychotic treatments were not able to change gene expressions in
      any of the regions evaluated. These findings provide evidence for the role of
      glutamatergic changes in schizophrenia-like phenotype of the SHR strain. 

PMID- 26296757
TI  - PAX2 promoted prostate cancer cell invasion through transcriptional regulation of
      HGF in an in vitro model.
AB  - Elucidating the mechanism of prostate cancer cell invasion may lead to the
      identification of novel therapeutic strategies for its treatment. Paired box 2
      (PAX2) and hepatocyte growth factor (HGF) proteins are promoters of prostate
      cancer cell invasion. We found that PAX2 protein activated the HGF gene promoter
      through histone H3 acetylation and upregulated HGF gene expression. Deletion
      analysis revealed that the region from -637 to -314 of the HGF gene was
      indispensable for HGF promoter activation by PAX2. This region contains consensus
      PAX2 binding sequences and mutations of the sequences attenuated HGF promoter
      activation. Using an in vitro invasion model, we found that PAX2 and HGF promoted
      prostate cancer cell invasion in the same pathway. Knockdown of HGF expression
      attenuated the cells' invasive capacity. Moreover, in tissue samples of human
      prostate cancers, HGF and PAX2 expression levels were positively correlated.
      These results suggested that upregulation of HGF gene expression by PAX2 enhanced
      the invasive properties of prostate cancer cells. The PAX2/HGF pathway in
      prostate cancer cells may be a novel therapeutic target in prostate cancer
      patients. 

PMID- 26296758
TI  - Campylobacter group II phage CP21 is the prototype of a new subgroup revealing a
      distinct modular genome organization and host specificity.
AB  - BACKGROUND: The application of phages is a promising tool to reduce the number of
      Campylobacter along the food chain. Besides the efficacy against a broad range of
      strains, phages have to be safe in terms of their genomes. Thus far, no genes
      with pathogenic potential (e.g., genes encoding virulence factors) have been
      detected in Campylobacter phages. However, preliminary studies suggested that the
      genomes of group II phages may be diverse and prone to genomic rearrangements.
      RESULTS: We determined and analysed the genomic sequence (182,761 bp) of group II
      phage CP21 that is closely related to the already characterized group II phages
      CP220 and CPt10. The genomes of these phages are comprised of four modules
      separated by very similar repeat regions, some of which harbouring open reading
      frames (ORFs). Though, the arrangement of the modules and the location of some
      ORFs on the genomes are different in CP21 and in CP220/CPt10. In this work, a PCR
      system was established to study the modular genome organization of other group II
      phages demonstrating that they belong to different subgroups of the CP220-like
      virus genus, the prototypes of which are CP21 and CP220. The subgroups revealed
      different restriction patterns and, interestingly enough, also distinct host
      specificities, tail fiber proteins and tRNA genes. We additionally analysed the
      genome of group II phage vB_CcoM-IBB_35 (IBB_35) for which to date only five
      individual contigs could be determined. We show that the contigs represent
      modules linked by long repeat regions enclosing some yet not identified ORFs
      (e.g., for a head completion protein). The data suggest that IBB_35 is a member
      of the CP220 subgroup. CONCLUSION: Campylobacter group II phages are diverse
      regarding their genome organization. Since all hitherto characterized group II
      phages contain numerous genes for transposases and homing endonucleases as well
      as similar repeat regions, it cannot be excluded that these phages are
      genetically unstable. To answer this question, further experiments and sequencing
      of more group II phages should be performed.

PMID- 26296759
TI  - Anthropogenic and biogenic sources of Ethylene and the potential for human
      exposure: A literature review.
AB  - This review examines available published information on ethylene emission
      sources, emission magnitudes, and inhalation exposures in order to assess those
      factors and circumstances that can affect human contact with this omnipresent
      gas. The results reveal that airborne ethylene concentrations at the ppb levels
      are commonplace and can arise in the vicinity of traffic corridors, forest fires,
      indoor kitchens, horticultural areas, oil fields, house fires, and petrochemical
      sites. The primary biogenic sources of ethylene derive from microbial activity in
      most soil and marine environments as well as its biological formation in wide
      variety of plant species. Sizable amounts of ethylene can also result from the
      burning of fossil fuels, forest and savanna fires, and crop residue combustion.
      Motor vehicle exhaust is the largest contributor to urban ethylene levels under
      most circumstances, but industrial flare releases and fugitive emissions may also
      be of relevance. Occupational exposures generally range up to about 50-100 ppm
      and have been documented for those working in the horticultural, petrochemical,
      and fire and rescue industries. Continuous personal monitoring at the community
      level has documented exposures of 3-4 ppb. These levels are more closely
      associated with the ethylene concentrations found indoors rather than outdoors
      indicating the importance of exposure sources found within the home. Indoor air
      sources of ethylene are associated with environmental tobacco smoke, wood or
      propane fuel use, fruit and vegetable storage, and cooking. Ethylene is not found
      in any consumer or commercial products and does not off-gas from building
      products to any appreciable extent. The review indicates that outdoor sources
      located some distance from the home do not make an appreciable contribution to
      personal exposures given the strength and variety of sources found in the
      immediate living environment. 

PMID- 26296760
TI  - The influence of p53 status on the cytotoxicity of fluorinated pyrimidine L
      nucleosides.
AB  - Fluorinated nucleoside analogues are a major class of cancer chemotherapy agents,
      and include the drugs 5-fluorouracil (5FU) and 5-fluoro-2'-deoxyuridine (FdUrd).
      The aim of this study was to examine the cellular toxicity of two novel
      fluorinated pyrimidine L-nucleosides that are enantiomers of D-nucleosides and
      may be able to increase selectivity for cancer cells as a result of their
      unnatural L-configuration. Two fluorinated pyrimidine L-nucleosides were examined
      in this study, L110 ([beta-L, beta-D]-5-fluoro-2'-deoxyuridine) and L117 (beta-L
      deoxyuridine:beta-D-5'-fluoro-2'-deoxyuridine). The cytotoxicity of these L
      nucleoside was determined in primary mouse fibroblasts and was compared with 5FU
      and FdUrd. In addition, the influence of p53 status on cytotoxicity was
      investigated. These cytotoxicity assays were performed on a matched set of
      primary mouse fibroblasts that were either wild type or null for the p53 tumour
      suppressor gene. It was found that cells lacking functional p53 were over 7500
      times more sensitive to the drugs L110, L117 and FdUrd than cells containing wild
      type p53.

PMID- 26296761
TI  - Phytol in a pharma-medico-stance.
AB  - This study aims to review phytol (PYT), through published articles, periodicals,
      magazines and patents, which were retrieved from the PM, SD, WS, SP; DII, WIPO,
      CIPO, USPTO and INPI databases. Among the 149 articles and 62 patents, 27.52%
      articles and 87.09% patients were found on the searched topic, PYT and its
      sources and synthesis and metabolism; then followed by 15.44% and 14.77% articles
      on PYT in cytotoxicity/cancer/mutagenicity/teratogenicity and PYT in neurological
      diseases, respectively. In the pharma-medico viewpoint, PYT and its derivatives
      have been evident to have antimicrobial, cytotoxic, antitumorous, antimutagenic,
      anti-teratogenic, antibiotic-chemotherapeutic, antidiabetic, lipid lowering,
      antispasmodic, anticonvulsant, antinociceptive, antioxidant, anti-inflammatory,
      anxiolytic, antidepressant, immunoadjuvancy, hair growth facilitator, hair fall
      defense and antidandruff activities. Otherwise, the important biometebolite of
      PYT is phytanic acid (PA). Evidence shows PA to have cytotoxic, anticancer,
      antidiabetic, lipid lowering and aniteratogenic activities. In addition, it may
      be considered as an important biomarker for some diseases such as Refsum's
      Disease (RD), Sjogren Larsson syndrome (SLS), rhizomelic chondrodysplasia
      punctata (RZCP), chronic polyneuropathy (CP), Zellweger's disease hyperpipecolic
      academia (ZDHA) and related diseases. Thus, phytol may be considered as a new
      drug candidate. 

PMID- 26296762
TI  - Reverse shoulder arthroplasty for proximal humerus fracture using a dedicated
      stem: radiological outcomes at a minimum 2 years of follow-up-case series.
AB  - BACKGROUND: Complex proximal humeral fractures are very difficult to treat
      particularly in patients older than 65 years with an osteoporotic bone and
      tuberosities compromised. The goal of this paper is to evaluate radiological
      outcomes at mid-term follow-up of proximal humerus fractures treated with reverse
      shoulder arthroplasty using a dedicated fracture stem. MATERIALS AND METHODS: The
      study population included 98 patients who underwent reverse shoulder with a
      dedicated fracture stem for an acute proximal humerus fracture; 87/98 patients
      were available for analysis. There were 62 female and 25 male patients, and the
      mean age was 76.2 years at the time of surgery (range 61-90 years). Clinical and
      radiological outcomes were evaluated at a mean follow-up of 27 months after
      surgery. RESULTS: Average active elevation was 137.7 degrees , external rotation
      29.1 degrees , and internal rotation 40.7 degrees . Overall, the tuberosity
      healing rate was 75 %. There was a significant increase in active anterior
      elevation, external rotation, and internal rotation among patients who
      demonstrated radiographic evidence of tuberosity healing. All tuberosity
      nonunions (21 cases) occurred preferentially in females, but this number did not
      reach statistical significance. CONCLUSION: RSP using a dedicated stem is a very
      viable solution to treat complex humerus proximal fracture. Reliable restoration
      of elevation can be expected. However, in patients in whom tuberosity healing
      occurs, a better active elevation other than restoration of active rotational
      movement can be observed.

PMID- 26296763
TI  - SCCmec IX in meticillin-resistant Staphylococcus aureus and meticillin-resistant
      coagulase-negative staphylococci from pigs and workers at pig farms in Khon Kaen,
      Thailand.
AB  - Livestock-associated meticillin-resistant Staphylococcus aureus, clonal complex
      (CC) 398, has been reported in Europe, whereas CC9 MRSA has mostly been found in
      Asia. Therefore, we aimed to detect MRSA on pig farms in north-eastern Thailand.
      A total of 257 nasal swabs (159 samples from pigs and 98 from pig-farm workers)
      were collected from three pig farms in north-eastern Thailand from 2010 to 2011.
      MRSA isolates were confirmed for femA and mecA genes by PCR. The MICs of eight
      antimicrobials, namely vancomycin (VA), cefazolin (CZ), ofloxacin (OF),
      tetracycline (TET), erythromycin (ER), oxacillin (OX), cefoxitin (FOX) and
      gentamicin (GN), were tested by agar dilution method. The virulence genes for
      Panton-Valentine leukocidin toxin (lukSF-PV), toxic shock syndrome toxin-1 (tst)
      and alpha-haemolysin (hla) were detected by PCR. Strain typing was performed by
      staphylococcal cassette chromosome (SCC) mec, agr, spa and multilocus sequence
      typing. Four MRSA were isolated: three from workers and one from a pig. All the
      MRSA isolates were resistant to OX, GN, ER, TET and CZ, and they all carried hla
      only. Two MRSA from humans carried SCCmec II-sequence type (ST)764-agrII, whereas
      the two remaining MRSA (one each from a human and a pig) contained SCCmec IX-ST9
      agrII. Interestingly, meticillin-resistant coagulase-negative Staphylococcus
      isolates carrying SCCmec IX were also obtained from five workers and three pigs.
      This study suggests that the SCCmec IX element is distributed among the
      Staphylococcus found in pigs and pig-farm workers, and pigs may be a reservoir
      for MRSA in the community. 

PMID- 26296764
TI  - Algimonas arctica sp. nov., isolated from intertidal sand, and emended
      description of the genus Algimonas.
AB  - A novel Gram-reaction-negative, aerobic, pale-orange-pigmented bacterium,
      designated strain SM1216T, was isolated from Arctic intertidal sand. Cells of
      strain SM1216T were dimorphic rods with a single polar prostheca or flagellum.
      The strain grew at 4 - 30  degrees C (optimum at 25  degrees C) and with 0.5 - 6
      % (w/v) NaCl (optimum with 2 - 3 %). It reduced nitrate to nitrite but did not
      hydrolyse gelatin, DNA or Tween 80. Phylogenetic analysis based on 16S rRNA gene
      sequences revealed that strain SM1216T was affiliated with the genus Algimonas in
      the family Hyphomonadaceae, sharing 97.5 and 96.3 % similarity with Algimonas
      ampicilliniresistens 14A-2-7T and Algimonas porphyrae 0C-2-2T, respectively, the
      two known species in the genus Algimonas. However, the level of DNA-DNA
      relatedness between strain SM1216T and the type strain of A.
      ampicilliniresistens, the nearest phylogenetic neighbour, was 57.9 %. The major
      cellular fatty acids of strain SM1216T were C18 : 1omega7c and C18 : 1 2-OH. The
      main polar lipids of strain SM1216T were monoglycosyldiglyceride (MGDG),
      glucuronopyranosyldiglyceride (GUDG), phosphatidylglycerol (PG) and three
      unidentified phospholipids (PL1-3). The major respiratory quinone was ubiquinone
      10 (Q10). The genomic G+C content of strain SM1216T was 60.6 mol%. On the basis
      of the evidence from this polyphasic study, strain SM1216T represents a novel
      species in the genus Algimonas, for which the name Algimonas arctica sp. nov. is
      proposed. The type strain is SM1216T ( = MCCC 1K00233T = KCTC 32513T). An emended
      description of the genus Algimonas is also given.

PMID- 26296765
TI  - Jatrophihabitans fulvus sp. nov., an actinobacterium isolated from grass soil.
AB  - A Gram-stain-positive, aerobic, non-motile, non-spore-forming, rod-shaped
      bacterium, designated strain PB158T, was isolated from grass soil sampled in
      Daejeon, Republic of Korea. Comparative 16S rRNA gene sequence studies placed the
      novel isolate in the class Actinobacteria, and most closely related to
      Jatrophihabitans endophyticus S9-650T and Jatrophihabitans soli KIS75-12T with
      98.1 and 97.0 % 16S rRNA gene sequence similarity, respectively. Cells of strain
      PB158T formed yellow colonies on R2A agar, contained MK-9(H4) as the predominant
      menaquinone, meso-diaminopimelic acid as the diagnostic diamino acid, and
      included iso-C16 : 0, C18 : 1omega9c, and C17 : 1omega8c as the major fatty acids
      (>5 %). The acyl type was found to be N-glycolylated. The G+C content of genomic
      DNA of strain PB158T was 72.4 mol%. In DNA-DNA hybridizations, the DNA-DNA
      relatedness value observed between strain PB158T and the type strain of J.
      endophyticus was 21.8 % indicating that the two strains do not belong to the same
      species. Thus, the combined genotypic and phenotypic data supported the
      conclusion that strain PB158T represents a novel species of the genus
      Jatrophihabitans, for which the name Jatrophihabitans fulvus sp. nov. is
      proposed. The type strain is PB158T ( = KCTC 33605T = JCM 30448T). 

PMID- 26296766
TI  - Transcription of malP is subject to phosphotransferase system-dependent
      regulation in Corynebacterium glutamicum.
AB  - The Gram-positive Corynebacterium glutamicum co-metabolizes most carbon sources
      such as the phosphotransferase system (PTS) sugar glucose and the non-PTS sugar
      maltose. Maltose is taken up via the ABC-transporter MusEFGK2I, and is further
      metabolized to glucose phosphate by amylomaltase MalQ, maltodextrin phosphorylase
      MalP, glucokinase Glk and phosophoglucomutase Pgm. Surprisingly, growth of C.
      glutamicum strains lacking the general PTS components EI or HPr was strongly
      impaired on the non-PTS sugar maltose. Complementation experiments showed that a
      functional PTS phosphorelay is required for optimal growth of C. glutamicum on
      maltose, implying its involvement in the control of maltose metabolism and/or
      uptake. To identify the target of this PTS-dependent control, transport
      measurements with 14C-labelled maltose, Northern blot analyses and enzyme assays
      were performed. The activities of the maltose transporter and enzymes MalQ, Pgm
      and GlK were not decreased in PTS-deficient C. glutamicum strains, which was
      corroborated by comparable transcript amounts of musE, musK and musG, as well as
      of malQ, in C. glutamicum DeltaptsH and WT. By contrast, MalP activity was
      significantly reduced and only residual amounts of malP transcripts were detected
      in C. glutamicum DeltaptsH when compared to WT. Promoter activity assays with the
      malP promoter in C. glutamicum DeltaptsH and WT confirmed that malP transcription
      is reduced in the PTS-deficient strain. Taken together, we show here for what is
      to the best of our knowledge the first time a regulatory function of the PTS in
      C. glutamicum and identify malP transcription as its target. 

PMID- 26296767
TI  - HCV upregulates Bim through the ROS/JNK signalling pathway, leading to Bax
      mediated apoptosis.
AB  - We previously reported that hepatitis C virus (HCV) infection induces Bax
      triggered, mitochondrion-mediated apoptosis by using the HCV J6/JFH1 strain and
      Huh-7.5 cells. However, it was still unclear how HCV-induced Bax activation. In
      this study, we showed that the HCV-induced activation and mitochondrial
      accumulation of Bax were significantly attenuated by treatment with a general
      antioxidant, N-acetyl cysteine (NAC), or a specific c-Jun N-terminal kinase (JNK)
      inhibitor, SP600125, with the result suggesting that the reactive oxygen species
      (ROS)/JNK signalling pathway is upstream of Bax activation in HCV-induced
      apoptosis. We also demonstrated that HCV infection transcriptionally activated
      the gene for the pro-apoptotic protein Bim and the protein expression of three
      major splice variants of Bim (BimEL, BimL and BimS). The HCV-induced increase in
      the Bim mRNA and protein levels was significantly counteracted by treatment with
      NAC or SP600125, suggesting that the ROS/JNK signalling pathway is involved in
      Bim upregulation. Moreover, HCV infection led to a marked accumulation of Bim on
      the mitochondria to facilitate its interaction with Bax. On the other hand,
      downregulation of Bim by siRNA (small interfering RNA) significantly prevented
      HCV-mediated activation of Bax and caspase 3. Taken together, these observations
      suggest that HCV-induced ROS/JNK signalling transcriptionally activates Bim
      expression, which leads to Bax activation and apoptosis induction. 

PMID- 26296768
TI  - Vibrio oceanisediminis sp. nov., a nitrogen-fixing bacterium isolated from an
      artificial oil-spill marine sediment.
AB  - A Gram-staining-negative, halophilic, facultatively anaerobic, motile, rod-shaped
      and nitrogen-fixing bacterium, designated strain S37T, was isolated from an
      artificial oil-spill sediment sample from the coast of Taean, South Korea. Cells
      grew at 10-37  degrees C and pH 5.0-9.0, with optimal growth at 28  degrees C and
      pH 6.0-8.0. Growth was observed with 1-9 % (w/v) NaCl in marine broth, with
      optimal growth with 3-5 % NaCl, but no growth was observed in the absence of
      NaCl. According to the results of 16S rRNA gene sequence analysis, strain S37T
      represents a member of the genus Vibrio of the class Gammaproteobacteria and
      forms a clade with Vibrio plantisponsor MSSRF60T (97.38 %), Vibrio diazotrophicus
      ATCC 33466T (97.31 %), Vibrio aestuarianus ATCC 35048T (97.07 %) Vibrio
      areninigrae J74T (96.76 %) and Vibrio hispanicus LMG 13240T (96.76 %). The major
      fatty acids were C16 : 0, C16 : 1omega7c/C16 : 1omega6c and C18 : 1omega7c/C18 :
      1omega6c. The DNA G+C content was 41.9 %. The DNA-DNA hybridization analysis
      results showed a 30.2 % association value with the closely related type strain V.
      plantisponsor DSM 21026T. On the basis of phenotypic and chemotaxonomic
      characteristics, strain S37T represents a novel species of the genus Vibrio, for
      which the name Vibrio oceanisediminis sp. nov., is proposed with the type strain
      S37T ( = KEMB 2255-005T = JCM 30409T). 

PMID- 26296770
TI  - The effect of dehydration on muscle metabolism and time trial performance during
      prolonged cycling in males.
AB  - This study combined overnight fluid restriction with lack of fluid intake during
      prolonged cycling to determine the effects of dehydration on substrate oxidation,
      skeletal muscle metabolism, heat shock protein 72 (Hsp72) response, and time
      trial (TT) performance. Nine males cycled at ~65% VO2peak for 90 min followed by
      a TT (6 kJ/kg BM) either with fluid (HYD) or without fluid (DEH). Blood samples
      were taken every 20 min and muscle biopsies were taken at 0, 45, and 90 min of
      exercise and after the TT. DEH subjects started the trial with a -0.6% BM from
      overnight fluid restriction and were dehydrated by 1.4% after 45 min, 2.3% after
      90 min of exercise, and 3.1% BM after the TT. There were no significant
      differences in oxygen uptake, carbon dioxide production, or total sweat loss
      between the trials. However, physiological parameters (heart rate [HR], rate of
      perceived exertion, core temperature [Tc], plasma osmolality [Posm], plasma
      volume [Pvol] loss, and Hsp72), and carbohydrate (CHO) oxidation and muscle
      glycogen use were greater during 90 min of moderate cycling when subjects
      progressed from 0.6% to 2.3% dehydration. TT performance was 13% slower when
      subjects began 2.3% and ended 3.1% dehydrated. Throughout the TT, Tc, Posm, blood
      and muscle lactate [La], and serum Hsp72 were higher, even while working at a
      lower power output (PO). The accelerated muscle glycogen use during 90 min of
      moderate intensity exercise with DEH did not affect subsequent TT performance,
      rather augmented Tc, RPE and the additional physiological factors were more
      important in slowing performance when dehydrated. 

PMID- 26296769
TI  - Expression profile of heat shock response factors during hookworm larval
      activation and parasitic development.
AB  - When organisms are exposed to an increase in temperature, they undergo a heat
      shock response (HSR) regulated by the transcription factor heat shock factor 1
      (HSF-1). The heat shock response includes the rapid changes in gene expression
      initiated by binding of HSF-1 to response elements in the promoters of heat shock
      genes. Heat shock proteins function as molecular chaperones to protect proteins
      during periods of elevated temperature and other stress. During infection,
      hookworm infective third stage larvae (L3) undergo a temperature shift from
      ambient to host temperature. This increased temperature is required for the
      resumption of feeding and activation of L3, but whether this increase initiates a
      heat shock response is unknown. To investigate the role of the heat shock in
      hookworm L3 activation and parasitic development, we identified and characterized
      the expression profile of several components of the heat shock response in the
      hookworm Ancylostoma caninum. We cloned DNAs encoding an hsp70 family member (Aca
      hsp-1) and an hsp90 family member (Aca-daf-21). Exposure to a heat shock of 42
      degrees C for one hour caused significant up-regulation of both genes, which
      slowly returned to near baseline levels following one hour attenuation at 22
      degrees C. Neither gene was up-regulated in response to host temperature (37
      degrees C). Conversely, levels of hsf-1 remained unchanged during heat shock, but
      increased in response to incubation at 37 degrees C. During activation, both hsp
      1 and daf-21 are down regulated early, although daf-21 levels increase
      significantly in non-activated control larvae after 12h, and slightly in
      activated larvae by 24h incubation. The heat shock response modulators celastrol
      and KNK437 were tested for their effects on gene expression during heat shock and
      activation. Pre-incubation with celastrol, an HSP90 inhibitor that promotes heat
      shock gene expression, slightly up-regulated expression of both hsp-1 and daf-21
      during heat shock. KNK437, an inhibitor of heat shock protein expression,
      slightly down regulated both genes under similar conditions. Both modulators
      inhibited activation-associated feeding, but neither had an effect on hsp-1
      levels in activated L3 at 16h. Both celastrol and KNK437 prevent the up
      regulation of daf-21 and hsf-1 seen in non-activated control larvae during
      activation, and significantly down regulated expression of the HSF-1 negative
      regulator Aca-hsb-1 in activated larvae. Expression levels of heat shock response
      factors were examined in developing Ancylostoma ceylanicum larvae recovered from
      infected hosts and found to differ significantly from the expression profile of
      activated L3, suggesting that feeding during in vitro activation is regulated
      differently than parasitic development. Our results indicate that a classical
      heat shock response is not induced at host temperature and is suppressed during
      larval recovery and parasitic development in the host, but a partial heat shock
      response is induced after extended incubation at host temperature in the absence
      of a developmental signal, possibly to protect against heat stress. 

PMID- 26296771
TI  - Diet-induced obesity impairs muscle satellite cell activation and muscle repair
      through alterations in hepatocyte growth factor signaling.
AB  - A healthy skeletal muscle mass is essential in attenuating the complications of
      obesity. Importantly, healthy muscle function is maintained through adequate
      repair following overuse and injury. The purpose of this study was to investigate
      the impact of diet-induced obesity (DIO) on skeletal muscle repair and the
      functionality of the muscle satellite cell (SC) population. Male C57BL/6J mice
      were fed a standard chow or high-fat diet (60% kcal fat; DIO) for 8 weeks.
      Muscles from DIO mice subjected to cardiotoxin injury displayed attenuated muscle
      regeneration, as indicated by prolonged necrosis, delayed expression of MyoD and
      Myogenin, elevated collagen content, and persistent embryonic myosin heavy chain
      expression. While no significant differences in SC content were observed, SCs
      from DIO muscles did not activate normally nor did they respond to exogenous
      hepatocyte growth factor (HGF) despite similar receptor (cMet) density.
      Furthermore, HGF release from crushed muscle was significantly less than that
      from muscles of chow fed mice. This study demonstrates that deficits in muscle
      repair are present in DIO, and the impairments in the functionality of the muscle
      SC population as a result of altered HGF/c-met signaling are contributors to the
      delayed regeneration. 

PMID- 26296772
TI  - The effect of exercise and beta2-adrenergic stimulation on glutathionylation and
      function of the Na,K-ATPase in human skeletal muscle.
AB  - Potassium and sodium displacements across the skeletal muscle membrane during
      exercise may cause fatigue and are in part controlled by the Na,K-ATPase.
      Regulation of the Na,K-ATPase is therefore important for muscle functioning. We
      investigated the effect of oxidative stress (glutathionylation) on Na,K-ATPase
      activity. Ten male subjects performed three bouts of 4-min submaximal exercise
      followed by intense exercise to exhaustion with and without beta2-adrenergic
      stimulation with terbutaline. Muscle biopsies were obtained from m. vastus
      lateralis at rest (Control samples) and at exhaustion. In vitro glutathionylation
      reduced (P < 0.05) maximal Na,K-ATPase activity in a dose-dependent manner. Na,K
      ATPase alpha subunits, purified by immunoprecipitation and tested by glutathione
      (GSH) antibodies, had a basal glutathionylation in Control samples and no further
      glutathionylation with exercise and beta2-adrenergic stimulation.
      Immunoprecipitation with an anti-GSH antibody and subsequent immunodetection with
      beta1 antibodies showed approximately 20% glutathionylation in Control samples
      and further glutathionylation after exercise (to 32%) and beta2-adrenergic
      stimulation (to 38%, P < 0.05). Combining exercise and beta2-adrenergic
      stimulation raised the beta1 glutathionylation to 45% (P < 0.05). In conclusion,
      both alpha and beta1 subunits of the Na,K-ATPase were glutathionylated in Control
      samples, which indicates that the maximal Na,K-ATPase activity is overestimated
      if based on protein density only. beta1 subunits are further glutathionylated by
      exercise and beta2-adrenergic stimulation. Our data suggest that
      glutathionylation contributes to the complex regulation of Na,K-ATPase function
      in human skeletal muscle. Glutathionylation of the Na,K-ATPase may explain
      reductions in maximal Na,K-ATPase activity after exercise, which may be involved
      in muscle fatigue. 

PMID- 26296773
TI  - Intrinsic apoptosis and proinflammatory cytokines regulated in human astrocytes
      infected with enterovirus 71.
AB  - Enterovirus 71 (EV71) has emerged as a clinically important neurotropic virus
      following poliovirus eradication. However, the mechanism of EV71-induced
      neurological manifestation remains largely unclear. In this study, we showed that
      human astrocytes were susceptible to EV71 and viral RNA was first detected at 12
      h post-infection (p.i.), whilst viral proteins were detected at 36 h p.i. EV71
      infected astrocytes underwent apoptosis, in which cytochrome c was released from
      mitochondria to the cytosol and caspase-9 was activated. Interestingly, caspase-2
      and -8 were not cleaved or activated during the infection, whilst a selective
      inhibitor of caspase-9, Z-LEHD-FMK, blocked the cleavage of caspase-3 and -7,
      indicating that only the mitochondria-mediated intrinsic apoptotic pathway was
      activated in EV71-infected astrocytes. EV71 infection also induced
      proinflammatory cytokines, including IL-6, IL-8, CCL5 and IFN-gamma-inducible
      protein (IP)-10 in astrocytes, which may play a critical role in EV71-induced
      neuroinflammation and neurological complications. By using inhibitors of mitogen
      activated protein kinases (MAPKs), we demonstrated that the induction of the
      cytokines was mainly regulated by the MAPK p38 signalling pathway as a
      significant reduction of the cytokines was observed when treated with p38
      inhibitors. This study demonstrated that human astrocytes were susceptible to
      EV71, and the infection led to intrinsic apoptosis and induction of p38-regulated
      proinflammatory cytokines. These findings further our understanding of the
      neuropathogenesis in severe cases of EV71 infection. 

PMID- 26296774
TI  - The role of regulation in the origin and synthetic modelling of minimal
      cognition.
AB  - In this paper we address the question of minimal cognition by investigating the
      origin of some crucial cognitive properties from the very basic organisation of
      biological systems. More specifically, we propose a theoretical model of how a
      system can distinguish between specific features of its interaction with the
      environment, which is a fundamental requirement for the emergence of minimal
      forms of cognition. We argue that the appearance of this capacity is grounded in
      the molecular domain, and originates from basic mechanisms of biological
      regulation. In doing so, our aim is to provide a theoretical account that can
      also work as a possible conceptual bridge between Synthetic Biology and
      Artificial Intelligence. In fact, we argue, Synthetic Biology can contribute to
      the study of minimal cognition (and therefore to a minimal AI), by providing a
      privileged approach to the study of these mechanisms by means of artificial
      systems.

PMID- 26296775
TI  - Information transfer through a signaling module with feedback: A perturbative
      approach.
AB  - Signal transduction in biological cells is effected by signaling pathways that
      typically include multiple feedback loops. Here we analyze information transfer
      through a prototypical signaling module with biochemical feedback. The module
      switches stochastically between an inactive and active state; the input to the
      module governs the activation rate while the output (i.e., the product
      concentration) perturbs the inactivation rate. Using a novel perturbative
      approach, we compute the rate with which information about the input is gained
      from observation of the output. We obtain an explicit analytical result valid to
      first order in feedback strength and to second order in the strength of input.
      The total information gained during an extended time interval is found to depend
      on the feedback strength only through the total number of activation/inactivation
      events. 

PMID- 26296776
TI  - Reclassification of Actinobacillus muris as Muribacter muris gen. nov., comb.
      nov.
AB  - To reinvestigate the taxonomy of [Actinobacillus] muris, 474 strains, mainly from
      mice and rats, were characterized by phenotype and 130 strains selected for
      genotypic characterization by 16S rRNA and partial rpoB gene sequencing. The type
      strain was further investigated by whole-genome sequencing. Phylogenetic analysis
      of the DNA sequences showed one monophyletic group with intragroup similarities
      of 96.7 and 97.2 % for the 16S rRNA and rpoB genes, respectively. The highest 16S
      rRNA gene sequence similarity to a taxon with a validly published name outside
      the group was 95.9 %, to the type strain of [Pasteurella] pneumotropica. The
      closest related taxon based on rpoB sequence comparison was 'Haemophilus
      influenzae-murium', with 88.4 % similarity. A new genus and a new combination,
      Muribacter muris gen. nov., comb. nov., are proposed based on a distinct
      phylogenetic position based on 16S rRNA and rpoB gene sequence comparisons, with
      major divergence from the existing genera of the family Pasteurellaceae. The new
      genus has the characteristics of [A.] muris with the emendation that acid
      formation from ( - )-d-mannitol and hydrolysis of aesculin are variable, while
      the alpha-glucosidase test is positive. There is no requirement for exogenously
      supplied NAD (V factor) for the majority of strains investigated; however, one
      strain was found to require NAD. The major fatty acids of the type strain of
      Muribacter muris were C14 : 0, C14 : 0 3-OH/iso-C16 : 1 I, C16 : 1omega7c and C16
      : 0, which is in line with most genera of the Pasteurellaceae. The type strain of
      Muribacter muris is CCUG 16938T ( = NCTC 12432T = ATCC 49577T). 

PMID- 26296777
TI  - Graphene oxide/manganese ferrite nanohybrids for magnetic resonance imaging,
      photothermal therapy and drug delivery.
AB  - Superparamagnetic manganese ferrite (MnFe2O4) nanoparticles have been deposited
      on graphene oxide (GO) by the thermal decomposition of manganese (II)
      acetylacetonate and iron (III) acetylacetonate precursors in triethylene glycol.
      The resulting GO/MnFe2O4 nanohybrids show very low cytotoxicity, negligible
      hemolytic activity, and imperceptible in vivo toxicity. In vitro and in vivo
      magnetic resonance imaging experiments demonstrate that GO/MnFe2O4 nanohybrids
      could be used as an effective T2 contrast agent. The strong optical absorbance in
      the near-infrared (NIR) region and good photothermal stability of GO/MnFe2O4
      nanohybrids result in the highly efficient photothermal ablation of cancer cells.
      GO/MnFe2O4 nanohybrids can be further loaded with doxorubicin (DOX) by pi-pi
      conjugate effect for chemotherapy. DOX release from GO/MnFe2O4 is significantly
      influenced by pH and can be triggered by NIR laser. The enhanced cancer cell
      killing by GO/MnFe2O4/DOX composites has been achieved when irradiated with near
      infrared light, suggesting that the nanohybrids could deliver both DOX
      chemotherapy and photothermal therapy with a synergistic effect. 

PMID- 26296778
TI  - Aberrant orbitofrontal connectivity in marijuana smoking adolescents.
AB  - INTRODUCTION: Orbitofrontal (OFC) circuits have been implicated in the
      pathophysiology of substance use disorders. The current study examined OFC
      functional connectivity differences in marijuana-using adolescents (MJ) and non
      using healthy controls (HC). METHODS: Functional magnetic resonance imaging
      (fMRI) resting-state data were obtained on a 3T MRI scanner on 31 HC and 43 heavy
      MJ smokers. Image analyses were performed between groups (MJ, HC) for the left
      and right OFC separately. Regression analyses between OFC functional connectivity
      and lifetime MJ use, age of first MJ use and impulsivity also were performed.
      RESULTS: Increased OFC functional connectivity to frontal and motor regions was
      observed in heavy MJ users compared to HC. Earlier age of first MJ use was
      associated with increased functional connectivity of the right OFC to motor
      regions. High lifetime MJ use was associated with increased OFC functional
      connectivity to posterior brain regions in MJ youth. DISCUSSION: Findings
      indicate atypical OFC functional connectivity patterns in attentional/executive,
      motor and reward networks in adolescents with heavy MJ use. These anomalies may
      be related to suboptimal decision making capacities and increased impulsivity.
      Results also suggest different OFC connectivity patterns may be present in
      adolescents with early onset of MJ use and high lifetime exposure to MJ.

PMID- 26296779
TI  - Neural correlates of error monitoring in adolescents prospectively predict
      initiation of tobacco use.
AB  - Deficits in self-regulation of behavior can play an important role in the
      initiation of substance use and progression to regular use and dependence. One of
      the distinct component processes of self-regulation is error monitoring, i.e.
      detection of a conflict between the intended and actually executed action. Here
      we examined whether a neural marker of error monitoring, Error-Related Negativity
      (ERN), predicts future initiation of tobacco use. ERN was assessed in a
      prospective longitudinal sample at ages 12, 14, and 16 using a flanker task. ERN
      amplitude showed a significant increase with age during adolescence. Reduced ERN
      amplitude at ages 14 and 16, as well as slower rate of its developmental changes
      significantly predicted initiation of tobacco use by age 18 but not transition to
      regular tobacco use or initiation of marijuana and alcohol use. The present
      results suggest that attenuated development of the neural mechanisms of error
      monitoring during adolescence can increase the risk for initiation of tobacco
      use. The present results also suggest that the role of distinct neurocognitive
      component processes involved in behavioral regulation may be limited to specific
      stages of addiction.

PMID- 26296780
TI  - Mesorhizobium waimense sp. nov. isolated from Sophora longicarinata root nodules
      and Mesorhizobium cantuariense sp. nov. isolated from Sophora microphylla root
      nodules.
AB  - In total 14 strains of Gram-stain-negative, rod-shaped bacteria were isolated
      from Sophora longicarinata and Sophora microphylla root nodules and authenticated
      as rhizobia on these hosts. Based on the 16S rRNA gene phylogeny, they were shown
      to belong to the genus Mesorhizobium, and the strains from S. longicarinata were
      most closely related to Mesorhizobium amorphae ACCC 19665T (99.8-99.9 %),
      Mesorhizobium huakuii IAM 14158T (99.8-99.9 %), Mesorhizobium loti USDA 3471T
      (99.5-99.9 %) and Mesorhizobium septentrionale SDW 014T (99.6-99.8 %), whilst the
      strains from S. microphylla were most closely related to Mesorhizobium ciceri UPM
      Ca7T (99.8-99.9 %), Mesorhizobium qingshengii CCBAU 33460T (99.7 %) and
      Mesorhizobium shangrilense CCBAU 65327T (99.6 %). Additionally, these strains
      formed two distinct groups in phylogenetic trees of the housekeeping genes glnII,
      recA and rpoB. Chemotaxonomic data, including fatty acid profiles, supported the
      assignment of the strains to the genus Mesorhizobium and allowed differentiation
      from the closest neighbours. Results of DNA-DNA hybridizations, MALDI-TOF MS
      analysis, ERIC-PCR, and physiological and biochemical tests allowed genotypic and
      phenotypic differentiation of our strains from their closest neighbouring
      species. Therefore, the strains isolated from S. longicarinata and S. microphylla
      represent two novel species for which the names Mesorhizobium waimense sp. nov.
      (ICMP 19557T = LMG 28228T = HAMBI 3608T) and Mesorhizobium cantuariense sp. nov.
      (ICMP 19515T = LMG 28225T = HAMBI 3604T), are proposed respectively.

PMID- 26296781
TI  - Structure of HIV-1 reverse transcriptase bound to a novel 38-mer hairpin template
      primer DNA aptamer.
AB  - The development of a modified DNA aptamer that binds HIV-1 reverse transcriptase
      (RT) with ultra-high affinity has enabled the X-ray structure determination of an
      HIV-1 RT-DNA complex to 2.3 A resolution without the need for an antibody Fab
      fragment or RT-DNA cross-linking. The 38-mer hairpin-DNA aptamer has a 15 base
      pair duplex, a three-deoxythymidine hairpin loop, and a five-nucleotide 5'
      overhang. The aptamer binds RT in a template-primer configuration with the 3'-end
      positioned at the polymerase active site and has 2'-O-methyl modifications at the
      second and fourth duplex template nucleotides that interact with the p66 fingers
      and palm subdomains. This structure represents the highest resolution RT-nucleic
      acid structure to date. The RT-aptamer complex is catalytically active and can
      serve as a platform for studying fundamental RT mechanisms and for development of
      anti-HIV inhibitors through fragment screening and other approaches.
      Additionally, the structure allows for a detailed look at a unique aptamer design
      and provides the molecular basis for its remarkably high affinity for RT.

PMID- 26296782
TI  - Inhibitory effect of silver nanoparticles mediated by atmospheric pressure air
      cold plasma jet against dermatophyte fungi.
AB  - In an in vitro study with five clinical isolates of dermatophytes, the MIC(50)
      and MIC(100) values of silver nanoparticles (AgNPs) ranged from 5 to 16 and from
      15 to 32 MUg ml(- 1), respectively. The combined treatment of AgNPs with
      atmospheric pressure-air cold plasma (APACP) induced a drop in the MIC(50) and
      MIC100 values of AgNPs reaching 3-11 and 12-23 MUg ml(- 1), respectively,
      according to the examined species. Epidermophyton floccosum was the most
      sensitive fungus to AgNPs, while Trichophyton rubrum was the most tolerant. AgNPs
      induced significant reduction in keratinase activity and an increase in the
      mycelium permeability that was greater when applied combined with plasma
      treatment. Scanning electron microscopy showed electroporation of the cell walls
      and the accumulation of AgNPs on the cell wall and inside the cells, particularly
      when AgNPs were combined with APACP treatment. An in vivo experiment with
      dermatophyte-inoculated guinea pigs indicated that the application of AgNPs
      combined with APACP was more efficacious in healing and suppressing disease
      symptoms of skin as compared with the application of AgNPs alone. The recovery
      from the infection reached 91.7 % in the case of Microsporum canis-inoculated
      guinea pigs treated with 13 MUg ml(- 1) AgNPs combined with APACP treatment
      delivered for 2  min. The emission spectra indicated that the efficacy of APACP
      was mainly due to generation of NO radicals and excited nitrogen molecules. These
      reactive species interact and block the activity of the fungal spores in vitro
      and in the skin lesions of the guinea pigs. The results achieved are promising
      compared with fluconazole as reference antifungal drug.

PMID- 26296783
TI  - Editor-oracle?

PMID- 26296784
TI  - The psychological impact of eyedrops administration in children.
AB  - PURPOSE: To determine the psychological effects of eyedrops administration in
      children. METHODS: Children requiring eyedrops for cycloplegic refraction were
      recruited in this cross-sectional study. Nurses administered eyedrops in 2-3
      cycles spaced 5-10 minutes apart, and optometrists performed refraction 30
      minutes after the last drop. Ophthalmologists, nurses, and optometrists rated the
      children's cooperation level at first review, after each eyedrop, at refraction,
      and at final review. Parents chose a personality type best describing their
      child, and monitored their child's anxiety using a modified Yale Preoperative
      Anxiety Scale (m-YPAS). Children were "uncooperative" if nurses noted significant
      distress during the first drop cycle. RESULTS: A total of 298 children 2-12 years
      of age were included. Of these, 77 (26%) experienced pre-drop distress and 39
      (13%) were uncooperative with drops. Compared to cooperative children,
      uncooperative children tended to be younger (2.0-4.9 years vs >=8 years; OR,
      4.11; 95% CI, 1.14-14.83; P = 0.031), male (OR, 2.55; 95% CI, 1.06-6.10; P =
      0.036), have had a previous negative eyedrop experience (84.2% vs 25.3%; P <
      0.001) and were more anxious (m-YPAS scores, 41.4 +/- 22.0 vs 30.6 +/- 12.6: P <
      0.001). Children described as "demanding and aggressive" were more uncooperative
      than "timid and anxious" children. It took longer to instill drops (3.1 vs 1.3
      minutes), and perform refraction (11.6 vs 7.2 minutes) in uncooperative children.
      CONCLUSIONS: A small group of children were uncooperative with eyedrops and 26%
      experienced significant pre-drop anxiety. Factors such as age, sex, a previous
      negative eyedrop experience, and pre-drop anxiety, associated with
      uncooperativeness need to be considered when developing strategies to improve the
      eyedrops experience in children.

PMID- 26296785
TI  - Lensectomy, vitrectomy, and transvitreal ciliary body photocoagulation as primary
      treatment for glaucoma in microspherophakia.
AB  - Microspherophakia is a rare, bilateral developmental anomaly of the crystalline
      lens. It can occur in isolation or as a component of a familial disorder. It has
      been associated with the Weill-Marchesani syndrome and Marfan syndrome. Angle
      clousure glaucoma can occur in microspherophakia and is the primary cause of
      visual loss. We describe the management of 2 sisters with bilateral
      microspherophakia and advanced angle closure glaucoma. 

PMID- 26296786
TI  - The cost-effectiveness of different strategies to evaluate optic disk drusen in
      children.

PMID- 26296787
TI  - Reply: To PMID 25266841.

PMID- 26296788
TI  - Incidence of retinopathy of prematurity in the middle Black Sea region of Turkey
      over a 10-year period.

PMID- 26296789
TI  - Reply: To PMID 25727579.

PMID- 26296791
TI  - Reply: To PMID 25727588.

PMID- 26296790
TI  - Effect of combining oblique muscle weakening procedures with bimedial rectus
      recessions on the surgical correction of esotropia.

PMID- 26296792
TI  - Lysobacter novalis sp. nov., isolated from fallow farmland soil.
AB  - A novel bacterial strain, designated THG-PC7(T), was isolated from fallow
      farmland soil in Yongin, South Korea. Cells of strain THG-PC7(T) were Gram-stain
      negative, dark yellow, aerobic, rod-shaped and had gliding motility. Strain THG
      PC7(T) grew optimally at 25-35  degrees C, at pH 7 and in the absence of NaCl.
      Comparative 16S rRNA gene sequence analysis identified strain THG-PC7(T) as
      belonging to the genus Lysobacter, exhibiting highest sequence similarity with
      Lysobacter ximonensis KCTC 22336(T) (98.7%) followed by Lysobacter niastensis
      KACC 11588(T) (95.7%). In DNA-DNA hybridization tests, DNA relatedness between
      strain THG-PC7(T) and its closest phylogenetic neighbour L. ximonensis was below
      25%. The DNA G+C content of the novel isolate was determined to be 62.5 mol%.
      Flexirubin-type pigments were found to be present. The major cellular fatty acids
      were determined to be iso-C15 : 0, iso-C16 : 0, anteiso-C15 : 0 and iso-C17 :
      1omega9c. The major respiratory quinone was identified as ubiquonone-8 (Q8). The
      predominant polar lipids were diphosphatidylglycerol, phosphatidylethanolamine,
      phosphatidylglycerol and an unidentified aminophospolipid. On the basis of
      results from DNA-DNA hybridization and the polyphasic data, strain THG-PC7(T)
      represents a novel species of the genus Lysobacter, for which the name Lysobacter
      novalis sp. nov. is proposed. The type strain is THG-PC7(T)( = KACC 18276(T) =
      CCTCC AB 2014319(T)).

PMID- 26296793
TI  - Effect of exogenous pulmonary surfactants on mortality rate in neonatal
      respiratory distress syndrome: A network meta-analysis of randomized controlled
      trials.
AB  - BACKGROUND: The utilization of multiple natural and synthetic products in
      surfactant replacement therapies in treatment of neonatal respiratory distress
      syndrome (NRDS) prompted us to take a closer looks at these various therapeutic
      options and their efficacies. The purpose of our study was to evaluate the
      effects of six exogenous pulmonary surfactants (EPS) (Survanta, Alveofact,
      Infasurf, Curosurf, Surfaxin and Exosurf) on mortality rate in NRDS by a network
      meta-analysis. METHODS: An exhaustive search of electronic databases was
      performed in PubMed, Ovid, EBSCO, Springerlink, Wiley, Web of Science, Cochrane
      Library, China National Knowledge Infrastructure, Wanfang and VIP databases (last
      updated search in October 2014) to retrieve randomized controlled trials (RCTs)
      relevant to our study topic. Published clinical trials were screened based on the
      following inclusion criteria: (1) study design: RCTs; (2) interventions:
      treatment with Survanta, Alveofact, Infasurf, Curosurf, Surfaxin or Exosurf for
      NRDS; (3) study subject: infants with NRDS confirmed by clinical diagnosis; (4)
      outcome: the mortality rate of infants with NRDS. Statistical analysis was
      performed using Stata 12.0 software (Stata Corporation, College Station, TX, USA)
      and Comprehensive Meta-analysis (CMA 2.0) software. RESULTS: From the 1840
      studies initially retrieved through database searches, a total of 17 high quality
      RCTs were selected for this network meta-analysis. The selected studies included
      a combined total of 57,223 infants with NRDS treated with various EPS (Survanta,
      27,017; Alveofact, 159; Infasurf, 20,377; Curosurf, 20,911; Surfaxin, 646;
      Exosurf, 1640). Network meta-analysis results showed that the mortality rates in
      NRDS infants treated with Alveofact, Infasurf, Curosurf, Surfaxin, Exosurf were
      not significantly different compared to Survanta (Alveofact: OR = 1.163, 95% CI =
      0.645-2.099, P = 0.616; Infasurf: OR = 0.985, 95% CI = 0.777-1.248, P = 0.897;
      Curosurf: OR = 0.789, 95% CI = 0.619-1.007, P = 0.056; Surfaxin: OR = 0.728, 95%
      CI = 0.477-1.112, P = 0.142; Exosurf: OR = 0.960, 95% CI = 0.698-1.319, P =
      0.799). Notably, the surface under the cumulative ranking curves (SUCRA) value in
      Surfaxin group was significantly higher than the other five groups (Surfaxin:
      80.4%; Survanta: 37.0%; Alveofact: 24.4%; Infasurf: 40.0%; Curosurf: 73.9%;
      Exosurf: 44.2%), suggesting that infant mortality rate in Surfaxin group was the
      lowest among the six EPS groups. CONCLUSION: Our study demonstrated that Surfaxin
      could effectively reduce the mortality rate of infants with NRDS and may have a
      better efficacy in NRDS treatment, compared to Survanta, Alveofact, Infasurf,
      Curosurf and Exosurf.

PMID- 26296795
TI  - Plan and road map for health reform in Iran.

PMID- 26296794
TI  - Roflumilast for asthma: Efficacy findings in mechanism of action studies.
AB  - BACKGROUND: The efficacy profile of roflumilast, a phosphodiesterase-4 inhibitor
      used for the treatment of chronic obstructive pulmonary disease (COPD), is well
      known. In asthma treatment, much less is understood about the role of
      roflumilast, particularly its mechanism of action and potential bronchodilatory
      effects. AIM: To evaluate the therapeutic efficacy and mechanism of action of
      roflumilast in patients with asthma using data from eight placebo-controlled,
      double-blind phase I-III studies. METHODS: The studies were conducted at 14 sites
      in Europe, North America and South Africa from 1997 to 2005. The effect of
      treatment with 250 MUg, 500 MUg or 1000 MUg roflumilast was compared with placebo
      in seven cross-over studies and one parallel-group study in 197 patients 18-70
      years of age. Primary endpoints focused on the extent of the late allergic
      response after an allergen challenge, change in sputum cell eosinophil counts or
      exhaled nitric oxide (eNO), forced expiratory volume in 1 s (FEV1) and exercise
      induced bronchoconstriction. Secondary endpoints included the extent of the early
      allergic response and measurements of tumour necrosis factor alpha (TNFalpha),
      sputum cells and inflammatory markers. RESULTS: Roflumilast attenuated allergen
      induced bronchoconstriction (FEV1) in patients with asthma. Significant
      reductions in allergen-induced airway inflammation, including a reduction in both
      eosinophil and neutrophil counts were also observed and physiologic responses to
      allergen-induced challenge were confirmed by a significant reduction in TNFalpha.
      Side effects were similar to COPD, but did not include weight loss. CONCLUSIONS:
      The results from these studies indicate that the anti-inflammatory effects of
      roflumilast observed in COPD are also seen in asthma and advance our
      understanding of its mechanism of action. All studies were funded by Takeda.
      Trial registration numbers available on ClinicalTrials.gov: NCT01365533.

PMID- 26296796
TI  - Early life origins of metabolic disease: Developmental programming of
      hypothalamic pathways controlling energy homeostasis.
AB  - A wealth of animal and human studies demonstrate that perinatal exposure to
      adverse metabolic conditions - be it maternal obesity, diabetes or under
      nutrition - results in predisposition of offspring to develop obesity later in
      life. This mechanism is a contributing factor to the exponential rise in obesity
      rates. Increased weight gain in offspring exposed to maternal obesity is usually
      associated with hyperphagia, implicating altered central regulation of energy
      homeostasis as an underlying cause. Perinatal development of the hypothalamus (a
      brain region key to metabolic regulation) is plastic and sensitive to metabolic
      signals during this critical time window. Recent research in non-human primate
      and rodent models has demonstrated that exposure to adverse maternal environments
      impairs the development of hypothalamic structure and consequently function,
      potentially underpinning metabolic phenotypes in later life. This review
      summarizes our current knowledge of how adverse perinatal environments program
      hypothalamic development and explores the mechanisms that could mediate these
      effects. 

PMID- 26296797
TI  - OsELF3-2, an Ortholog of Arabidopsis ELF3, Interacts with the E3 Ligase APIP6 and
      Negatively Regulates Immunity against Magnaporthe oryzae in Rice.

PMID- 26296798
TI  - The Intrinsically Disordered Protein BKI1 Is Essential for Inhibiting BRI1
      Signaling in Plants.

PMID- 26296799
TI  - Hierarchical multi-class SVM with ELM kernel for epileptic EEG signal
      classification.
AB  - In this paper, a novel hierarchical multi-class SVM (H-MSVM) with extreme
      learning machine (ELM) as kernel is proposed to classify electroencephalogram
      (EEG) signals for epileptic seizure detection. A clinical EEG benchmark dataset
      having five classes, obtained from Department of Epileptology, Medical Center,
      University of Bonn, Germany, is considered in this work for validating the
      clinical utilities. Wavelet transform-based features such as statistical values,
      largest Lyapunov exponent, and approximate entropy are extracted and considered
      as input to the classifier. In general, SVM provides better classification
      accuracy, but takes more time for classification and also there is scope for a
      new multi-classification scheme. In order to mitigate the problem of SVM, a novel
      multi-classification scheme based on hierarchical approach, with ELM kernel, is
      proposed. Experiments have been conducted using holdout and cross-validation
      methods on the entire dataset. Metrics namely classification accuracy,
      sensitivity, specificity, and execution time are computed to analyze the
      performance of the proposed work. The results show that the proposed H-MSVM with
      ELM kernel is efficient in terms of better classification accuracy at a lesser
      execution time when compared to ANN, various multi-class SVMs, and other research
      works which use the same clinical dataset. 

PMID- 26296800
TI  - Estimation of dynamic metabolic activity in micro-tissue cultures from sensor
      recordings with an FEM model.
AB  - We estimated the dynamic cell metabolic activity and the distribution of the pH
      value and oxygen concentration in tissue samples cultured in vitro by using real
      time sensor records and a numerical simulation of the underlying reaction
      diffusion processes. As an experimental tissue model, we used chicken spleen
      slices. A finite element method model representing the biochemical processes and
      including the relevant sensor data was set up. By fitting the calculated results
      to the measured data, we derived the spatiotemporal values of the pH value, the
      oxygen concentration and the absolute metabolic activity (extracellular
      acidification and oxygen uptake rate) of the samples. Notably, the location of
      the samples in relation to the sensors has a great influence on the detectable
      metabolic rates. The long-term vitality of the tissue samples strongly depends on
      their size. We further discuss the benefits and limitations of the model. 

PMID- 26296801
TI  - Finite element study on the anatomic transtibial technique for single-bundle
      anterior cruciate ligament reconstruction.
AB  - The anatomic transtibial (TT) technique is proposed as a new approach for single
      bundle anterior cruciate ligament (ACL) reconstruction. Geometric models of the
      anatomic TT and anteromedial (AM) portal techniques were fabricated with a
      reconstructed knee joint model and virtual surgical operations. Grafts of 7 mm
      diameter were modeled and inserted into tunnels drilled in each model. In the
      models, the shape of the graft between the femur and the tibia, the lengths of
      the bone tunnels, and the femoral graft bending angles were evaluated. To
      evaluate the biomechanical effects of both techniques on the grafts, the contact
      pressures and maximum principal stresses in the grafts were calculated using the
      finite element method. The anatomic TT technique placed the femoral tunnel to the
      anatomic position of the native ACL femoral attachment site. In addition, it
      decreased the peak contact pressure and the maximum principal stress at the full
      extension position of the graft compared with the AM portal technique. The
      anatomic TT technique may be regarded as a superior surgical technique compared
      with the conventional TT and AM portal techniques. Because of the easy surgical
      operation involved, the technique decreases the operation time for ACL
      reconstruction and it provides a deformation behavior of grafts similar to that
      in the native ACL in a knee joint. With its few side effects, the anatomic TT
      technique may considerably help patients.

PMID- 26296802
TI  - Glenohumeral range of motion (ROM) and isometric strength of professional team
      handball athletes, part III: changes over the playing season.
AB  - INTRODUCTION: The aim of our study was to investigate the relation of workload on
      range of motion and isometric strength of team handball athletes' shoulders over
      a competitive season. MATERIALS AND METHODS: 31 Professional male handball
      athletes underwent clinical shoulder examinations. Athletes were examined
      subsequently during the complete playing season (week 0, 6, 22 and 40) to
      determine bilateral isometric shoulder rotational strength and active range of
      motion (ROM). In addition, relative (intraclass correlation coefficients (ICC)
      and absolute (standard error of measurement) reliability were calculated.
      RESULTS: Intraobserver reliability was excellent (ICC 0.76-0.98) for isometric
      strength and flexibility measurements. Internal rotation (IR) and total arc ROM
      in the throwing shoulder (TS) decreased significantly (p < 0.05) in both
      sequences (week 22 to week 40, week 0 to week 40). External rotation (ER) ROM and
      isometric strength in IR and ER did not change significantly. Glenohumeral
      internal rotation deficit (GIRD) and external rotation gain (ERG) of the TS
      decreased significantly between week 22 and week 40, but both did not change
      overall (week 0 to week 40). There was significant influence on IR ROM (week 22
      to week 40) and strength in ER (week 0 to week 40) in the non-throwing shoulder.
      CONCLUSIONS: Several characteristics of handball players' shoulders changed
      significantly from the beginning to the end of a season. More specifically, the
      repetitive forces accumulated during the competitive season resulted in altered
      GIRD, ERG and isometric strength of the dominant glenohumeral joint.

PMID- 26296803
TI  - [Dose management in radiology: Review of the technological status].
AB  - BACKGROUND: The Euratom directive 2013/59 ("EU directive for radiation
      protection") has to be implemented into national law by spring 2018 and requires
      a complete recording of patient dosages and relevant parameters. Additionally, a
      medical physics expert has to be consulted for each radiological examination
      above a defined threshold. OBJECTIVES: A complete recording of the dosage
      administered from all modalities and optimization of the radiological procedures
      should result in a reduction of the total dosage. MATERIAL AND METHODS: This can
      be achieved by automated systems that incorporate not only the detection of the
      dose parameters but also the evaluation and analysis of these data. When provided
      with warning levels such a system should be able to inform or warn the operator
      when dose thresholds have been exceeded or even better inform the operator about
      possible excess dosages before an examination. Depending on the information
      provided by the modality, dose management systems can operate at different levels
      in the picture archiving and communication system (PACS), radiological and
      hospital information systems (RIS/HIS) or with the header information of a
      digital imaging and communications in medicine (DICOM) image and evaluate and
      analyze this data. CONCLUSION: A practicable use of such systems is only possible
      by close cooperation of medical personnel, medical physicists and information
      technology (IT) administrators. Various systems are available commercially or
      free but an individual adaptation of these systems is useful and necessary,
      depending on the requirements of the radiology practice or hospital.

PMID- 26296804
TI  - [MR implant labelling and its use in clinical MRI practice].
AB  - Before a magnetic resonance imaging (MRI) examination, implants in patients must
      be cleared for MR safety in order to exclude the risk of possible severe injuries
      and implant malfunction in an MR environment. The general contraindication for
      measurements of patients with implants still applies; however, in the recent past
      a way has been found to legally circumvent this contraindication. For this
      purpose special conditions are required: explicit implant identification and the
      original manufacturer's labelling are necessary, the required conditions for
      conditionally MR safe implants must be assured and a risk-benefit analysis with
      appropriate explanation to the patient has to be performed. This process can be
      very complex as the implants are often poorly documented and detailed information
      on the implant MR labelling is also often outdated or not easy to interpret. This
      article provides information about legal and normative principles of MR
      measurement of patients with implants. The possible physical interactions with
      implants will be briefly dealt with as well as possible strategies for better
      identification and investigation of implants and MR labelling. General approaches
      for minimizing the risk will be discussed using some examples. The second part
      deals with the content of MR implant labelling and the current test standards.
      Furthermore, the additional information from the operating instructions of the MR
      scanner that are necessary for the interpretation of the MR implant labelling,
      will be explained. The article concludes with an explanation of the current
      pattern for MR labelling of implants from the U.S. Food and Drug Administration
      (FDA) and an exemplary application. 

PMID- 26296805
TI  - [Orbit: Part 1: anatomy, imaging procedures and retrobulbar lesions].
AB  - The aim of this 2-part review article on diseases of the orbit is to give the
      reader an insight into the anatomical structure and an overview of the most
      important diseases in the area of the eye socket. The main focus is on a
      description of the imaging procedures and their individual advantages and
      disadvantages. The most important tumors, trauma and degenerative alterations of
      the orbit are also described. 

PMID- 26296806
TI  - Intra-individual comparison of carotid and femoral atherosclerotic plaque
      features with in vivo MR plaque imaging.
AB  - The purpose of this study was to evaluate differences of plaque composition and
      morphology within the same patient in different vascular beds using non-invasive
      MR-plaque imaging. 28 patients (67.8 +/- 7.4 years, 8 females) with high
      Framingham general cardiovascular disease 10-year risk score and mild-to-moderate
      atherosclerosis were consecutively included in the study. All subjects underwent
      a dedicated MRI-plaque imaging protocol using TOF and T1w and T2w black-blood
      sequences with fat suppression at 1.5 T. The scan was centered on the carotid
      bulb of the carotid arteries and on the most stenotic lesion of the ipsilateral
      femoral artery, respectively. Plaques were classified according to the American
      Heart Association (AHA) lesion type classification and area measurements of
      lumen, wall and the major plaque components, such as calcification, necrotic core
      and hemorrhage were determined in consensus by two blinded reviewers using
      dedicated software (Cascade, Seattle, USA). Plaque components were recorded as
      maximum percentages of the wall area. Carotid arteries had larger maximum wall
      and smaller minimum lumen areas (p < 0.001) than femoral arteries, whereas no
      significant difference was find with respect to the max. NWI (p = 0.87).
      Prevalence of lipid-rich AHA lesion type IV/V and complicated AHA lesion type VI
      with hemorrhage/thrombus/fibrous cap rupture was significantly higher in the
      carotid arteries compared to the femoral arteries. Plaque composition as
      percentage of the vessel wall differed significantly between carotid and femoral
      arteries: Max. %necrotic core and max. %hemorrhage were significantly higher in
      the carotid arteries compared to the femoral arteries (p = 0.001 and p = 0.02,
      respectively). Max. %calcification did not differ significantly. Average stenotic
      degree of carotid arteries at duplex was 49.7 +/- 12.5 (%). Non-invasive MR
      plaque-imaging is able to visualize differences in plaque composition across the
      vascular tree. We observed significant differences in quantitative and
      qualitative plaque features between carotid and femoral arteries within the same
      patient, which in the future could help to improve risk stratification in
      patients with atherosclerosis.

PMID- 26296807
TI  - Birth defects after assisted reproductive technology according to the method of
      treatment in Japan: nationwide data between 2004 and 2012.
AB  - OBJECTIVES: The purpose of the present study was to analyze birth defects
      (congenital anomalies) after assisted reproductive technology (ART) according to
      the method of treatment, namely in vitro fertilization (IVF), intracytoplasmic
      sperm injection (ICSI) and frozen-thawed embryo transfer (FET). METHODS:
      Individual lists of all ART pregnancies resulting in birth defects from birth
      year 2004 to 2012 presented in the annual reports by the Japan Society of
      Obstetrics and Gynecology were used as the initial sources of information.
      Relative risks (RRs) with the corresponding 95 % confidence intervals (CIs) were
      calculated with IVF as the reference group when calculating RR of ICSI for IVF,
      and with FET as the reference group when calculating the RR of fresh embryo
      transfer for FET. RESULTS: In total, 2725 stillbirths or live births with birth
      defects were analyzed. The prevalence of birth defects was slightly yet
      significantly higher in ICSI compared with IVF throughout the study period (RR =
      1.15, 95 % CI 1.02-1.29) and in the 2004-2006 period (RR = 1.26, 95 % CI 1.00
      1.58). The prevalence of birth defects was significantly higher for fresh embryo
      transfer compared with FET in the 2004-2006 period (RR = 1.39, 95 % CI 1.12
      1.72). The prevalence of birth defects in multiple births was significantly lower
      in fresh embryo transfer compared with FET (RR = 0.70, 95 % CI 0.55-0.90, live
      births of 2007-2012). CONCLUSIONS: The present descriptive epidemiological study
      suggests that the impacts of different ART methods on birth defects might differ.

PMID- 26296808
TI  - Additive mixed effect model for recurrent gap time data.
AB  - Gap times between recurrent events are often of primary interest in medical and
      observational studies. The additive hazards model, focusing on risk differences
      rather than risk ratios, has been widely used in practice. However, the marginal
      additive hazards model does not take the dependence among gap times into account.
      In this paper, we propose an additive mixed effect model to analyze gap time
      data, and the proposed model includes a subject-specific random effect to account
      for the dependence among the gap times. Estimating equation approaches are
      developed for parameter estimation, and the asymptotic properties of the
      resulting estimators are established. In addition, some graphical and numerical
      procedures are presented for model checking. The finite sample behavior of the
      proposed methods is evaluated through simulation studies, and an application to a
      data set from a clinic study on chronic granulomatous disease is provided.

PMID- 26296809
TI  - The neonicotinoid imidacloprid, and the pyrethroid deltamethrin, are antagonists
      of the insect Rdl GABA receptor.
AB  - A mutation in the second transmembrane domain of the GABA receptor subunit, Rdl,
      is associated with resistance to insecticides such as dieldrin and fipronil.
      Molecular cloning of Rdl cDNA from a strain of the malaria mosquito, Anopheles
      gambiae, which is highly resistant to dieldrin revealed this mutation (A296G) as
      well as another mutation in the third transmembrane domain (T345M). Wild-type,
      A296G, T345M and A296G + T345M homomultimeric Rdl were expressed in Xenopus
      laevis oocytes and their sensitivities to fipronil, deltamethrin, 1,1,1-trichloro
      2,2-bis(p-chlorophenyl) ethane (DDT), imidacloprid and spinosad were measured
      using two-electrode voltage-clamp electrophysiology. Spinosad and DDT had no
      agonist or antagonist actions on Rdl. However, fipronil, deltamethrin and
      imidacloprid decreased GABA-evoked currents. These antagonistic actions were
      either reduced or abolished with the A296G and the A296G + T345M mutations while
      T345M alone appeared to have no significant effect. In conclusion, this study
      identifies another mutation in the mosquito Rdl that is associated with
      insecticide resistance. While T345M itself does not affect insecticide
      sensitivity, it may serve to offset the structural impact of A296G. The present
      study also highlights Rdl as a potential secondary target for neonicotinoids and
      pyrethroids. We show for the first time that deltamethrin (a pyrethroid
      insecticide) and imidacloprid (a neonicotinoid insecticide) act directly on the
      insect GABA receptor, Rdl. Our findings highlight Rdl as a potential secondary
      target of pyrethroids and neonicotinoids mutations in which may contribute to
      resistance to these widely used insecticides.

PMID- 26296810
TI  - Prognostic Value of Quantitative Diffusion-Weighted MRI in Patients with
      Traumatic Brain Injury.
AB  - BACKGROUND AND PURPOSE: Data about the predictive value of quantitative diffusion
      weighted MRI in traumatic brain injury (TBI) patients is lacking. This study
      aimed to determine if specific apparent diffusion coefficient (ADC) thresholds
      could be determined that correlate with outcome in moderate-severe TBI. METHODS:
      This retrospective observational study investigated patients with moderate-severe
      TBI. MRIs obtained post-injury days 1-13 were analyzed. MRIs were obtained on a
      1.5T scanner; 20-23 contiguous diffusion-weighted imaging (DWI) sections with a
      spin-echo echo planar imaging DWI 256*256 reconstructed matrix; field of view
      24*24 cm; slice thickness/gap of 5/1.5 or 5/2.5 mm. The ADC value of each brain
      tissue voxel was determined. The percentage of voxels below different ADC
      thresholds was calculated and correlated with outcome. A good outcome was defined
      as discharge to home or a rehabilitation facility. RESULTS: Seventy-six patients
      were analyzed. Thirty-five patients (46%) had a good outcome. The timing of MRI
      scans did not differ between groups, but the mean age did (42+/-18 years vs. 56+/
      19 years, p<.01, good vs. poor outcome). Patients with poor outcome had
      significantly higher percentage of brain volume with ADC < 400*10(-6) mm2 /second
      (.85+/-.67% vs. .60+/-.29%, poor vs. good outcome, p<.05). Using a ROC curve
      analysis and Youden's index, an ADC <400*10(-6) mm2 /second in >=.49% of brain
      was 85% sensitive and 46% specific for poor outcome (p<.05). CONCLUSIONS:
      Quantitative MRI offers additional prognostic information in acute TBI. A whole
      brain tissue ADC threshold of <400*10(-6) mm2 /second in >=.49% of brain may be a
      novel prognostic biomarker.

PMID- 26296812
TI  - Inception of Acetic Acid/Water Cluster Growth in Molecular Beams.
AB  - The influence of carboxylic acids on water nucleation in the gas phase has been
      explored in the supersonic expansion of water vapour mixed with acetic acid (AcA)
      at various concentrations. The sodium-doping method has been used to detect
      clusters produced in supersonic expansions by using UV photoionisation. The mass
      spectra obtained at lower acid concentrations show well-detected Na(+) -AcA(H2O)n
      and Na(+)-AcA2 (H2O)n clusters up to 200 Da and, in the best cooling expansions,
      emerging Na(+)-AcAm (H2O)n signals at higher masses and unresolved signals that
      extend beyond m/e values >1000 Da. These signals, which increase with increasing
      acid content in water vapour, are an indication that the cluster growth taking
      place arises from mixed water-acid clusters. Theoretical calculations show that
      small acid-water clusters are stable and their formation is even
      thermodynamically favoured with respect to pure water clusters, especially at
      lower temperatures. These findings suggest that acetic acid may play a
      significant role as a pre-nucleation embryo in the formation of aerosols in wet
      environments.

PMID- 26296811
TI  - Performance of NiTi endodontic instrument under different temperatures.
AB  - The purpose of this study was to test nickel titanium (NiTi) instrument
      performance under different surrounding temperatures. Twenty-four superelastic
      NiTi instruments with a conical shape comprising a 0.30-mm-diameter tip and 0.06
      taper were equally divided into 3 groups according to the temperature employed.
      Using a specially designed cyclic fatigue testing apparatus, each instrument was
      deflected to give a curvature 10 mm in radius and a 30 degrees  angle. This
      position was kept as the instrument was immersed in a continuous flow of water
      under a temperature of 10, 37, or 50  degrees C for 20 s to calculate the
      deflecting load (DL). In the same position, the instrument was then allowed to
      rotate at 300 rpm to fracture, and the working time was converted to the number
      of cycles to fracture (NCF). The statistical significance was set at p = 0.05.
      The mean DL (in N) and NCF (in cycles) of the groups at 10, 37, and 50  degrees C
      were 10.16 +/- 1.36 and 135.50 +/- 31.48, 13.50 +/- 0.92 and 89.20 +/- 16.44, and
      14.70 +/- 1.21 and 65.50 +/- 15.90, respectively. The group at 10  degrees C had
      significantly the lowest DL that favorably resulted in the highest NCF. Within
      the limitations of this study, the surrounding temperature influences the cyclic
      fatigue resistance and DL of the superelastic NiTi instruments. Lower
      temperatures are found to favorably decrease the DL and extend the lifetime of
      the superelastic NiTi instrument. Further NiTi instrument failure studies should
      be performed under simulated body temperature. 

PMID- 26296813
TI  - Polymerization kinetics and impact of post polymerization on the Degree of
      Conversion of bulk-fill resin-composite at clinically relevant depth.
AB  - OBJECTIVE: Since bulk-fill (BF) resin composites should cure efficiently to a
      depth up to 4mm, the aim of the study was to determine the time-dependence of
      degree of conversion (DC) at that depth during 24h post-irradiation. METHODS:
      Eight representative BF resin composites were studied [x-tra base (XTB), Venus
      Bulk Fill (VBF), Tetric EvoCeram Bulk Fill (TECBF), Sonic Fill (SF), Filtek Bulk
      Fill (FBF), everX Posterior (eXP), Beautifil-Bulk Flowable (BBF), Beautifil-Bulk
      Restorative (BBR)]. Specimens were fabricated in white Delrin moulds of 4mm
      height and 5mm internal diameter directly on an attenuated total reflectance
      (ATR) accessory attachment of an (FTIR) spectrometer (Nicolet iS50, Thermo
      Fisher, Madison, USA). Upper specimen surfaces were irradiated in situ for 20 s
      with an LED curing unit (Elipar S10 with average tip irradiance of 1200
      mW/cm(2)). Spectra from the lower surface were recorded continuously in real-time
      for 5 min and then at 30 and 60 min and 24h post irradiation. RESULTS: Mean
      ranges of DC4mm (%) of the materials at 4mm depth were 39-67; 48-75; 45-74; and
      50-72 at 5, 30 and 60 min and 24h respectively. DCs for XTB, VBF, TECBF, FBF, BBR
      increased significantly 30 min after irradiation (p<0.05) and were not affected
      by subsequent time up to 24h (p>0.05). DC for SF was not affected by subsequent
      time after 5 min (p>0.05). For eXP and BBF, DC increased 24h after irradiation
      (p<0.05). The data were described by the superposition of two exponential
      functions characterising the gel phase (described by parameters a, b) and the
      glass phase (described by parameters c and d). SIGNIFICANCE: Post polymerization
      impact of bulk-fill composites is material dependent. Five materials exhibited
      their maximum DC4mm already 30 min after starting the irradiation while DC4mm for
      two materials optimized after 24h. BF materials were found to exhibit after 24h a
      DC between 50 and 72% at 4mm depth under the stated irradiation conditions.

PMID- 26296814
TI  - Chemical bonding and electronic localization in a Ga(I) amide.
AB  - The electron density in a one-coordinate [Ga(I) N(SiMe3 )R] complex has been
      determined from ab initio calculations and multipole modeling of 90 K X-ray data.
      The topologies of the Laplacian distribution and the ELI-D match a situation
      having an sp(3) -hybridized nitrogen with a tetrahedral arrangement of two single
      sigma-bonds (to carbon and silicon) and two lone pairs pointing towards gallium
      in a scissor-grasping fashion. The analysis of the Laplacian distribution
      furthermore reveals a ligand-induced charge concentration (LICC) in the outer
      core of gallium oriented directly towards the nitrogen atom, and thus in between
      the two lone pairs. These observations might suggest that the trigonal planar
      nitrogen geometry result from a dative Ga?N bond, in which the roles of the metal
      and the ligand have been reversed with respect to a "standard" metal-ligand
      interaction, that is, the metal is here electron-donating. The ELI-D reveals a
      diffuse and directional lone pair on gallium, suggesting that this complex could
      serve as a sigma-donor. 

PMID- 26296815
TI  - At 5 years, transcatheter aortic valve replacement had similar rates of mortality
      and stroke as surgical aortic valve replacement in high-risk patients.

PMID- 26296816
TI  - Locomotive biomechanics in persons with chronic ankle instability and lateral
      ankle sprain copers.
AB  - OBJECTIVES: To compare the locomotive biomechanics of participants with chronic
      ankle instability (CAI) to those of lateral ankle sprain (LAS) copers. DESIGN:
      Cross-sectional study. METHODS: Twenty-eight participants with CAI and 42 LAS
      copers each performed 5 self-selected paced gait trials. 3-D lower extremity
      temporal kinematic and kinetic data were collected for these participants from
      200ms pre- to 200ms post-heel strike (period 1) and from 200ms pre- to 200ms post
      toe off (period 2). RESULTS: The CAI group displayed increased hip flexion
      bilaterally during period 1 compared to LAS copers. During period 2, CAI
      participants exhibited reduced hip extension bilaterally, increased knee flexion
      bilaterally and increased ankle inversion on the 'involved' limb. They also
      displayed a bilateral decrease in the flexor moment pattern at the knee.
      CONCLUSIONS: Considering that all of the features which distinguished CAI
      participants from LAS copers were also evident in our previously published
      research (within 2-weeks following acute first-time LAS); these findings
      establish a potential link between these features and long-term outcome following
      first-time LAS. Clinicians must be cognizant of the capacity for these movement
      and motor control impairments to cascade proximally from the injured joint up the
      kinetic chain and recognise the value that gait re-training may have in
      rehabilitation planning to prevent CAI.

PMID- 26296818
TI  - ERRATUM TO Membrane Rafts in the Erythrocyte Membrane: A Novel Role of MPP1p55.

PMID- 26296817
TI  - Regulation of renal phosphate handling: inter-organ communication in health and
      disease.
AB  - In this review, we focus on the interconnection of inorganic phosphate (Pi)
      homeostasis in the network of the bone-kidney, parathyroid-kidney, intestine
      kidney, and liver-kidney axes. Such a network of organ communication is important
      for body Pi homeostasis. Normalization of serum Pi levels is a clinical target in
      patients with chronic kidney disease (CKD). Particularly, disorders of the
      fibroblast growth factor 23/klotho system are observed in early CKD.
      Identification of phosphaturic factors from the intestine and liver may enhance
      our understanding of body Pi homeostasis and Pi metabolism disturbances in CKD
      patients. 

PMID- 26296819
TI  - Elm leaves 'warned' by insect egg deposition reduce survival of hatching larvae
      by a shift in their quantitative leaf metabolite pattern.
AB  - Plants may take insect eggs on their leaves as a warning of future herbivory and
      intensify their defence against feeding larvae. Responsible agents are, however,
      largely unknown, and little knowledge is available on this phenomenon in
      perennial plants. We investigated how egg deposition affects the anti-herbivore
      defence of elm against the multivoltine elm leaf beetle. Prior egg deposition
      caused changes in the quality of feeding-damaged leaves that resulted in
      increased larval mortality and reduced reproductive capacity of the herbivore by
      harming especially female larvae. Chemical analyses of primary and secondary leaf
      metabolites in feeding-damaged, egg-free (F) and feeding-damaged, egg-deposited
      (EF)-leaves revealed only small differences in concentrations when comparing
      metabolites singly. However, a pattern-focused analysis showed clearly separable
      patterns of (F) and (EF)-leaves because of concentration differences in
      especially nitrogen and phenolics, of which robinin was consumed in greater
      amounts by larvae on (EF) than on (F)-leaves. Our study shows that insect egg
      deposition mediates a shift in the quantitative nutritional pattern of feeding
      damaged leaves, and thus might limit the herbivore's population growth by
      reducing the number of especially female herbivores. This may be a strategy that
      pays off in a long run particularly in perennial plants against multivoltine
      herbivores. 

PMID- 26296820
TI  - Guidelines for Future Use?

PMID- 26296821
TI  - Urinary Neutrophil Gelatinase-Associated Lipocalin as Predictor of Short- or Long
      Term Outcomes in Cardiac Surgery Patients.
AB  - OBJECTIVES: To determine the ability of urinary neutrophil gelatinase-associated
      lipocalin (uNGAL) to predict cardiac surgery-associated acute kidney injury (CSA
      AKI), continuous renal replacement therapy (CRRT), mortality, and a composite
      outcome of major adverse kidney events at 365 days (MAKE365), and to investigate
      the influence of cardiopulmonary bypass (CPB) on NGAL release. DESIGN: A
      prospective observational study. SETTING: A single-center university hospital.
      PARTICIPANTS: A cohort of 288 adult cardiac surgery patients. INTERVENTIONS:
      uNGAL was measured at baseline, immediately after surgery, and on days 1 and 2
      postoperatively. The authors used the recent Kidney Disease Improving Global
      Outcomes consensus criteria to define CSA-AKI. MEASUREMENTS AND MAIN RESULTS: CSA
      AKI occurred in 36.1% of patients. uNGAL rapidly became significantly higher in
      patients who developed AKI, with peak value immediately after surgery (349.9
      [76.6-1446.6] v 90.1 [20.8-328] ng/mg creatinine; p<0.001). No measure of uNGAL
      (peak, postsurgery, day 1 or 2 postsurgery) accurately predicted CSA-AKI, CRRT,
      mortality, or MAKE365. However, immediately after surgery, CPB induced greater
      uNGAL release compared with off-pump surgery (265.5 umol/L [71-989.6] v 48.7
      ng/mg creatinine [17-129.8]; p<0.001). Moreover, such early uNGAL release
      correlated with CPB duration (r = 0.505; p<0.001) but not with peak serum
      creatinine values on day 3 or 7 after surgery. CONCLUSIONS: uNGAL had a limited
      predictive ability for CSA-AKI or other relevant clinical outcomes after cardiac
      surgery and appeared to be more closely related to the use and duration of CPB.
      Thus, its levels may represent the aggregate effect of an inflammatory response
      to CPB as well as a renal response to cardiac surgery and inflammation.

PMID- 26296822
TI  - Validity of Thromboelastometry for Rapid Assessment of Fibrinogen Levels in
      Heparinized Samples During Cardiac Surgery: A Retrospective, Single-center,
      Observational Study.
AB  - OBJECTIVE: To assess the validity of fibrinogen assay of rotational
      thromboelastometry (FIBTEM)-derived estimates of fibrinogen in samples collected
      during cardiopulmonary bypass in cardiac surgical patients by comparison to
      Clauss method fibrinogen concentration. DESIGN: Retrospective observational
      study. SETTING: Single university hospital center. PARTICIPANTS: Human
      participants. INTERVENTIONS: Retrospectively obtained laboratory assays including
      rotational thromboelastometry (ROTEM) and Clauss fibrinogen assay. MEASUREMENTS
      AND MAIN RESULTS: A retrospective review was performed of anesthesia records at a
      single university teaching hospital during a 1-year period. From paired samples
      taken near the end of cardiopulmonary bypass, fibrinogen concentrations (Clauss
      method) were compared with FIBTEM-derived measures of maximal clot firmness (MCF)
      and clot amplitude at 10 minutes (A10) using Spearman's rank correlation, linear
      regression, and receiver operating characteristic curve analysis. The study
      included 1,077 patients. Clauss fibrinogen was correlated strongly with FIBTEM
      amplitudes (r = 0.78 for MCF and A10; p<0.01). The correlation was related
      inversely to hemoglobin concentration (p<0.01). The area under the receiver
      operating characteristic curve was 0.95; the optimal FIBTEM A10 cutoff for
      diagnosis of a fibrinogen concentration of<1.5 g/L was <=8 mm. CONCLUSIONS: The
      FIBTEM was a valid point-of-care method for estimating the fibrinogen
      concentration during cardiopulmonary bypass and may be used for prediction of
      hypofibrinogenemia before separation from the extracorporeal circuit.

PMID- 26296823
TI  - In Reference to "Air" in the Aortic Arch After Cannulation for Cardiopulmonary
      Bypass: Devastating Complication or Benign Explanation?

PMID- 26296824
TI  - Reply to R. M. Lynch: "Guidelines for widespread use?".

PMID- 26296825
TI  - Focused Transthoracic Cardiac Ultrasound: A Survey of Training Practices.
AB  - OBJECTIVE: The role of focused assessment by transthoracic echocardiography or
      focused cardiac ultrasound (FoCUS) in the perioperative setting is uncertain and
      evolving. To the authors' knowledge, there are no studies that evaluate the
      current teaching practices regarding FoCUS in US anesthesiology residencies. The
      authors surveyed residents and residency program directors to examine the
      frequency, type, and variability of instruction regarding training of FoCUS.
      DESIGN: A survey study. SETTING: Anesthesiology residency programs in the United
      States. PARTICIPANTS: All 133 Accreditation Council for Graduate Medical
      Education anesthesiology program directors and their residents were invited to
      participate in an anonymous electronic survey. MEASUREMENTS AND MAIN RESULTS: In
      all, 292 respondents replied to the survey, and 245 were included in the
      analysis. Overall response rate was 30% for program directors. The majority of
      the respondents were trainees (83.7%). FoCUS training was reported to be present
      by 36% of respondents. Respondents from institutions in which>10% of attending
      physicians used FoCUS were nearly 3 times as likely as those in which fewer
      attending physicians used FoCUS to report presence of FoCUS training program. The
      most common training mode is lectures with simulation (34%), followed by bedside
      training (31%). The most frequently reported responsible training parties were
      anesthesiologists (75%), followed by cardiologists (14%). Although FoCUS training
      is relatively rare, most respondents (187 of 205 residents and 26 of 40 program
      directors) said that FoCUS should be the standard in training for anesthesia
      residents. CONCLUSIONS: Despite the increasing availability and use of ultrasound
      in clinical practice, FoCUS-related use and training remain uncommon in
      anesthesiology. Trainees in anesthesiology are not receiving adequate instruction
      in FoCUS despite their desire to acquire this skill.

PMID- 26296826
TI  - Very Transient Cases of Acute Kidney Injury in the Early Postoperative Period
      After Cardiac Surgery: The Relevance of More Frequent Serum Creatinine Assessment
      and Concomitant Urinary Biochemistry Evaluation.
AB  - OBJECTIVE: To evaluate if more frequent serum creatinine (sCr) measurements in
      the early postoperative period (first 48 hours) after cardiac surgery would help
      in early diagnosis of acute kidney injury (AKI), as well as reveal cases of AKI
      duration of fewer than 24 hours (vtAKI). The sequential blood and urinary
      biochemical profile of patients who developed vtAKI was compared with that of the
      patients who did not develop AKI or who developed AKI for more than 48 hours
      (pAKI). DESIGN: A retrospective analysis of prospectively collected data.
      SETTING: Two intensive care units of 2 private hospitals. PARTICIPANTS: Twenty
      nine patients who underwent cardiac surgery who had 6 values of serum creatinine
      (sCr) measured within the first 48 hours after surgery and concomitant spot urine
      samples for urine biochemistry assessment. INTERVENTIONS: None. MEASUREMENTS AND
      MAIN RESULTS: Eighteen patients (62%) developed Acute Kidney Injury Network
      (AKIN) sCr-based AKI, half of them for fewer than 24 hours. Most AKI patients had
      the sCr increase diagnosed 6 to 12 hours after surgery. When comparing the
      sequential alterations of blood and urinary parameters among patients with no
      AKI, vtAKI, and pAKI, the authors found that most of them were similar among
      groups, differing only in magnitude and duration. CONCLUSIONS: More frequent sCr
      measurements in the early postoperative period, together with urine biochemistry
      assessment, have the potential to anticipate AKI diagnosis after cardiac surgery
      and reveal cases of very transient AKI usually not diagnosed in current practice.
      The clinical relevance of these findings must be evaluated in larger, prospective
      studies.

PMID- 26296827
TI  - New Beginnings.

PMID- 26296829
TI  - School Nurse Workload--Staffing for Safe Care: Position Statement.
AB  - It is the position of the National Association of School Nurses (NASN) that daily
      access to a registered professional school nurse (hereinafter referred to as a
      school nurse) can significantly improve students' health, safety, and abilities
      to learn. To meet the health and safety needs of students, families, and school
      communities, school nurse workloads should be determined at least annually, using
      student- and community-specific health data.

PMID- 26296831
TI  - The role of interventional radiology in complications associated with liver
      transplantation.
AB  - The evolution of liver transplantation (LT) from an unusual procedure to a
      practical therapeutic option for patients with life-threatening liver diseases
      has brought with it several unique challenges. Although the patient survival
      rates have been steadily improving, with more complex surgeries being performed
      and increasing duration of graft survival, the overall post LT complication rate
      continues to stay high. They include inflow complications related to portal vein
      (PV) or hepatic artery, outflow complications related to hepatic vein or inferior
      vena cava, biliary leaks or strictures, postoperative collections or abscesses,
      graft rejection or post-transplant malignancy. These post-transplant
      complications provide a fertile ground for interventional radiology (IR) to
      flourish as it can contribute towards the management of each of these, and on
      most occasions, except for in graft rejection, it can circumvent a major surgery
      or even re-transplantation. The minimally invasive nature and lower morbidity
      associated with IR procedures make them preferable to similar surgical
      procedures. In post-transplant biliary complications, IR and therapeutic
      endoscopy have almost completely replaced surgery as the first-line treatments.
      The same can be said regarding the important role that IR plays in the management
      of most non-acute vascular complications. Meanwhile, more evidence and experience
      needs to be accumulated in the endovascular treatment of acute vascular
      complications encountered in the early post-operative period. This review
      primarily focuses on the various IR strategies in the management of the LT
      related vascular and biliary complications with illustrative cases. 

PMID- 26296832
TI  - The association of muscle and tendon elasticity with passive joint stiffness: In
      vivo measurements using ultrasound shear wave elastography.
AB  - BACKGROUND: Passive joint stiffness is associated with various tissues, including
      muscles, tendons, ligaments, and joint capsules. The specific elasticity of
      muscles or tendons can be measured using ultrasound shear wave elastography. To
      examine the association of muscle and tendon elasticity with passive joint
      stiffness, in vivo measurements of muscle and tendon elasticity were performed
      using ultrasound shear wave elastography. METHODS: In 25 subjects, passive ankle
      joint stiffness was determined using the joint angle-passive torque relationship.
      The stiffness index of the muscle belly of the medial gastrocnemius (MG)-
      influenced by the muscle fascicles, its aponeuroses, and the proximal tendon--was
      quantified by the displacement of the muscle-tendon junction, which was
      visualized using B-mode ultrasonography during passive dorsiflexion. The
      stiffness index of the Achilles tendon--influenced by the tendon and the
      ligaments and joint capsule of the ankle--was similarly determined. The MG and
      Achilles tendon elasticity was measured using ultrasound shear wave elastography.
      FINDINGS: Simple regression indicated a significant correlation between passive
      joint stiffness and stiffness index of the MG muscle belly (r=0.80) and Achilles
      tendon (r=0.60), but no correlation with elasticity of the MG (r=-0.37) or
      Achilles tendon (r=-0.39). INTERPRETATION: Individual variations in the
      elasticity of either the MG or Achilles tendon are not associated with variations
      in passive ankle joint stiffness; however, variations in the elasticity of other
      tissues, including MG aponeuroses or the ligaments and joint capsule of the
      ankle, would be associated with the variations in joint stiffness.

PMID- 26296833
TI  - Are Medical Students Who Want to Become Surgeons Different? An International
      Cross-Sectional Study.
AB  - INTRODUCTION: Surgery is one of the most demanding and competitive medical
      specialities. This study aims to identify the characteristics that medical
      students who aspire to surgical specialisation possess. MATERIALS AND METHODS: In
      February 2010, an online survey comprised 36 questions was produced with the aid
      of the open source survey tool Limesurvey (Version 1.85 RC3). Deans' offices and
      student organisations in eight countries were contacted via e-mail with a link to
      the online survey for them to disseminate amongst the student population.
      Respondents were grouped into "Surgically inclined" and "non-surgically
      inclined". To compare the characteristics of these two groups, the Fisher Exact
      test was used for categorical data and non-parametric tests were used for
      continuous data. RESULTS: Between February and June 2010, we received 2907
      responses; the majority from Australia, Austria, Germany, Switzerland and the UK.
      Of these, 2351 indicated what discipline they would like to pursue after
      graduation, with 383 (16.3 %) favouring surgery. The percentages of students
      interested in Surgery were similar across all participating countries. Those
      favouring Surgery were 1.5 times more likely to be male (*p = 0.01); however,
      Austria and Germany had significantly higher rates of female students interested
      in Surgery than all other countries surveyed. Students favouring Surgery were 20
      % more likely to be single. Students favouring surgery were more likely to
      nominate "social prestige" and "remuneration" as their key motivation to become a
      doctor and were also prepared to work longer hours than respondents that were not
      surgically inclined. CONCLUSION: In this study, Medical students who aspire
      toward surgical careers were more likely to be male, less lifestyle orientated,
      and seeking social prestige and financial remuneration compared to other medical
      students.

PMID- 26296834
TI  - Emergency Management of Gallbladder Disease: Are Acute Surgical Units the New
      Gold Standard?
AB  - INTRODUCTION: Since 2011, all acute general surgical admissions have been managed
      by the consultant-led emergency general surgery service (EGS) at our institution.
      We aim to compare EGS management of acute biliary disease to its preceding model.
      MATERIALS AND METHODS: Retrospective review of prospectively collated databases
      was performed to capture consecutive emergency admissions with biliary disease
      from 1st February 2009 to 31st January 2013. Patient demographics, surgical
      intervention, use of diagnostic radiology, histological diagnosis, complications
      and hospital length of stay (LOS) were retrieved. RESULTS: A total of 566
      patients were included (pre-EGS 254 vs. EGS 312). In the EGS period, the number
      of patients having surgery on index admission increased from 43.7 to 58.7 % (p <
      0.001) as did use of intra-operative cholangiography from 75.7 to 89.6 % (p =
      0.003). The conversion to open cholecystectomy rate also was reduced from 14.4 to
      3.3 % (p < 0.001). Overall, a 14 % reduction in use of multiple (>1) imaging
      modalities for diagnosis was noted (p = 0.003). There was a positive trend in
      reduction of bile leaks but no significant difference in the overall morbidity
      and mortality. Time to theatre was reduced by 1 day [pre-EGS 2.7 (IQR 1.5-5.0)
      vs. EGS 1.7 (IQR 1.2-2.6) p < 0.001]. The overall hospital LOS was reduced by 1.5
      days [pre-EGS 5.0 (IQR 3-7) vs. EGS 3.5 (IQR 2-5) p < 0.001]. CONCLUSION: Since
      the advent of EGS, more judicious use of diagnostic radiology, reduced
      complications, reduced LOS, reduced time to theatre and an increased rate of
      definitive management during the index admission were demonstrated.

PMID- 26296835
TI  - Risk of New-Onset Dyslipidemia After Laparoscopic Adrenalectomy in Patients with
      Primary Aldosteronism.
AB  - BACKGROUND: Many patients with primary aldosteronism (PA) show a significant
      decline in kidney function after adrenalectomy. Thus, PA patients who undergo
      surgery are at greater risk of both postoperative renal damage and new-onset
      metabolic events associated with renal insufficiency. The aim of this study was
      to explore postoperative changes in serum lipid levels and to identify risk
      factors associated with postoperative new-onset dyslipidemia in PA patients.
      METHODS: The records of 57 Japanese patients who underwent unilateral
      laparoscopic adrenalectomy for PA were retrospectively surveyed. Clinical and
      biochemical data were evaluated at baseline and 12 months after surgery.
      Preoperative and postoperative estimated glomerular filtration (eGFR) and serum
      lipid profile, including triglycerides, high-density lipoprotein (HDL)
      cholesterol and low-density lipoprotein (LDL)-cholesterol levels, were compared.
      Furthermore, uni- and multivariate analyses were performed to determine the
      predictors for postoperative new-onset dyslipidemia. RESULTS: A significant
      decrease in eGFR and deterioration of serum lipid levels was identified
      postoperatively in most patients. Of the 39 patients without pre-existing
      dyslipidemia, 18 developed new-onset dyslipidemia postoperatively. Multivariate
      analysis identified preoperative lower eGFR and higher body mass index as
      independent predictors for new-onset dyslipidemia after surgery. On univariate
      analyses, additional factors associated with new-onset dyslipidemia included
      older age, male sex, higher LDL-cholesterol, and higher LDL/HDL ratio.
      CONCLUSIONS: PA patients had a higher risk of postoperative new-onset or
      progressive dyslipidemia. Clinicians should pay attention to not only follow-up
      of renal impairment but also total management of new-onset metabolic events
      associated with renal insufficiency in PA patients.

PMID- 26296836
TI  - What are the True Advantages of Devices for Hepatic Parenchymal Transection in
      Open Surgery? Reply.

PMID- 26296837
TI  - Classification of Intraoperative Complications: Reply.

PMID- 26296838
TI  - Surgical and Radiological Studies on the Length of the Hepatic Ducts.
AB  - BACKGROUND: Right-sided hepatectomy is often selected for perihilar
      cholangiocarcinoma, due to the anatomic consideration that "the left hepatic duct
      is longer than that of the right hepatic duct". However, only one study briefly
      mentioned the length of the hepatic ducts. Our aim is to investigate whether the
      consideration is correct. METHODS: In surgical study, the lengths of the resected
      bile duct were measured using pictures of the resected specimens in 475
      hepatectomized patients with perihilar cholangiocarcinoma. In radiological study,
      the estimated lengths of the bile duct to be resected were measured using
      cholangiograms reconstructed from computed tomography images in 61 patients with
      distal bile duct obstruction. RESULTS: In surgical study, the length of the
      resected left hepatic duct was 25.1 +/- 6.4 mm in right trisectionectomy (n = 37)
      and 14.9 +/- 5.7 mm in right hepatectomy (n = 167). The length of the right
      hepatic duct was 14.1 +/- 5.7 mm in left hepatectomy (n = 149) and 21.3 +/- 6.4
      mm in left trisectionectomy (n = 122). In radiological study, the lengths of the
      bile duct corresponding to the surgical study were 34.1 +/- 7.8, 22.4 +/- 7.1,
      20.8 +/- 4.8, and 31.6 +/- 5.3 mm, respectively. Both studies determined that the
      lengths of the resected bile ducts were (1) similar between right and left
      hepatectomies, (2) significantly shorter in right hepatectomy than in left
      trisectionectomy, and (3) the longest in right trisectionectomy. CONCLUSIONS: The
      aforementioned anatomical assumption is a surgeon's biased view. Based on our
      observations, a flexible procedure selection is recommended.

PMID- 26296839
TI  - Documentation of Pregnancy Status, Gynaecological History, Date of Last Menstrual
      Period and Contraception Use in Emergency Surgical Admissions: Time for a Change
      in Practice?
AB  - OBJECTIVE: To determine whether pregnancy status, gynaecological history, date of
      last menstrual period and contraceptive use are documented in emergency female
      admissions of reproductive age admitted to general surgery. DESIGN: This is a
      retrospective study. SETTING: This study was conducted in the United Kingdom.
      POPULATION: Females of reproductive age (12-50 years) admitted as an emergency to
      general surgery with abdominal pain were considered in this study. METHODS:
      Retrospective analysis of medical notes of emergency female admissions with
      abdominal pain between January and September 2012. We recorded whether a
      pregnancy test result was documented (cycle 1). Results were analysed and a
      prompt added to the medical clerk-in document. We re-audited (cycle 2) between
      January and June 2013 looking for improvement. MAIN OUTCOME MEASURES: Documented
      pregnancy status within 24 h of admission and prior to any surgical intervention.
      RESULTS: 100 case notes were reviewed in stage 1. 30 patients (30 %) had a
      documented pregnancy status. 32 (32 %), 25 (25 %) and 29 (29 %) had a documented
      gynaecology history, contraceptive use and date of last menstrual period (LMP),
      respectively. 24 patients underwent emergency surgery, 6 (25 %) had a documented
      pregnancy status prior to surgery. Of 50 patients reviewed in stage 2, 37 (75.0
      %) had a documented pregnancy status (p < 0.001), with 41 (82 %) having both
      gynaecological history (p < 0.0001) and contraceptive use (p < 0.0001)
      documented. 40 patients (80 % had a documented LMP (p < 0.0001). 7 patients
      required surgery, of whom 6 (85.7 %) had a documented pregnancy test prior to
      surgery (p = 0.001). All pregnancy tests were negative. CONCLUSIONS: A simple
      prompt in the surgical admission document has significantly improved the
      documentation of pregnancy status and gynaecological history in our female
      patients, particularly in those who require surgical intervention. A number of
      patient safety concerns were addressed locally, but require a coordinated,
      interdisciplinary discussion and a national guideline. A minimum standard of
      care, in females of reproductive age, should include mandatory objective
      documentation of pregnancy status, whether or not they require surgical
      intervention.

PMID- 26296840
TI  - Prognostic Significance of Muscle Attenuation in Pancreatic Cancer Patients
      Treated with Neoadjuvant Chemoradiotherapy.
AB  - BACKGROUND: Emerging evidences have gradually revealed the skeletal muscle
      attenuation (MA) was not only reflected the accumulation of lipids in skeletal
      muscle but also associated with physiological and pathological states. The aim of
      this study was to evaluate the impact of MA on the prognosis of pancreatic cancer
      patients treated with neoadjuvant chemoradiotherapy (NACRT). METHODS: Eighty
      three patients with pancreatic cancer who received NACRT were enrolled. Patients
      were divided according to their Hounsfield units of the skeletal muscle at the
      third lumbar vertebra in CT. The lower quartile was defined as MA group and the
      remainder as control group. RESULTS: There was no significant difference in
      overall survival between pre-NACRT MA and control groups. In contrast, patients
      with post-NACRT MA had a significantly poorer prognosis than patients without.
      The patients in the post-NACRT MA group were significantly older than patients in
      the control group. There were no significant differences in most
      clinicopathological and perioperative factors between both groups. However,
      patients with post-NACRT MA had a longer hospital stay than patients without.
      Furthermore, the incompletion rate of the proposed adjuvant chemotherapy was
      significantly higher in the MA group than control. Importantly, multivariate
      analysis indicated that post-NACRT MA was an independent prognostic factor.
      CONCLUSIONS: Muscle attenuation may have a significant impact in pancreatic
      cancer patients treated with multimodal therapy. Therefore, our data may provide
      new insights into perioperative patient care to improve the prognosis of
      resectable pancreatic cancer.

PMID- 26296841
TI  - Complications in Laparoscopic Versus Open Incisional Ventral Hernia Repair. A
      Retrospective Comparative Study.
AB  - PURPOSE: The objective of the study was to evaluate peri- and postoperative
      outcomes, especially severe complications in adult incisional ventral hernia
      repair performed by open or laparoscopic surgery. METHODS: Adult patients who
      were operated for incisional ventral hernias in two tertiary hospitals in Finland
      during 2006-2012 were included in the study. Clinical data were collected from
      patient registers. Peri- and postoperative parameters were gathered and compared
      between open and laparoscopic groups. Postoperative complications were analyzed,
      and the focus was on major complications. RESULTS: The results of 818
      hernioplasties were evaluated: 291 (36.3 %) open and 527 (63.7 %) laparoscopic
      operations. In the laparoscopic group, the number of patients with postoperative
      complications was slightly lower (18.4 vs. 23.4 %, p = 0.090), and there were
      significantly fewer surgical site infections (3.2 vs. 8.6 %, p = 0.001). Twelve
      major complications occurred. In the laparoscopic group, four of the five major
      complications were consequences of undetected enterotomies, leading to
      reoperations, longer hospital stays, and death of one patient. Major
      complications in the open group consisted of four cardiac infarctions and three
      septic surgical site infections. Complex adhesions had a significant influence on
      major complications, enterotomies, and surgical site infections. Laparoscopic
      operations had a lower mean blood loss (13 vs. 31.5 ml, p = 0.028), and hospital
      stay (4 vs. 6 days, p = 0.001) compared to open operations. CONCLUSIONS:
      Laparoscopic incisional ventral hernia repair has a low rate of postoperative
      complications but it is associated with an increased risk of undetected
      enterotomies, in particular during cases involving adhesiolysis.

PMID- 26296843
TI  - Robert Condon MD FACS 1929-2015: In Memory.

PMID- 26296842
TI  - Clinical Significance of Sentinel Node Positivity in Patients with Superficial
      Esophageal Cancer.
AB  - BACKGROUND: Sentinel node (SN) mapping in esophageal cancer has been reported to
      be technically feasible with an acceptable detection rate and accuracy. However,
      the clinical significance and survival analysis findings associated with the
      metastatic status of SNs in patients with early-stage esophageal cancer have not
      been clarified. In this study, we investigated the clinical significance and
      survival impact of SN mapping in early-stage esophageal cancer. METHODS: Among
      patients who were diagnosed preoperatively with clinical T1N0M0 or T2N0M0
      esophageal cancer and who underwent SN mapping, 70 consecutive patients who were
      diagnosed with pathological T1 primary thoracic esophageal cancer were enrolled
      in this study. Sixty-four (91 %) patients were diagnosed with squamous cell
      carcinoma while 5 (7 %) patients were with adenocarcinoma. Endoscopic injection
      of technetium-99m tin colloid was performed before surgery, and radioactive SNs
      were identified by preoperative lymphoscintigraphy and intraoperative gamma
      probing. Standard esophagectomy with lymphadenectomy was performed in all
      patients, and all resected nodes were evaluated by routine pathological
      examination. RESULTS: SNs were successfully detected in 65 (92.9 %) of 70
      patients with pT1 esophageal cancer. The sensitivity to predict lymph node
      metastasis was 91.7 %, and the diagnostic accuracy based on SN status was 96.9 %.
      Although there was a wide distribution of SNs from cervical to abdominal areas,
      84.5 % of the patients had no lymph node metastasis or had lymph node metastasis
      only in SN. The disease-specific survival of the patients with metastatic non-SNs
      was significantly worse relative to that of the patients with no lymph node
      metastasis or lymph node metastasis only in SN. CONCLUSIONS: This study
      demonstrated that radio-guided SN mapping is useful not only as an accurate
      diagnostic tool for detecting lymph node metastasis but also as a tool for
      prognostic stratification in patients with cN0 early esophageal cancer.

PMID- 26296844
TI  - National Kidney Foundation/Council on Renal Nutrition Message From the
      Chairperson.

PMID- 26296845
TI  - PATIENT EDUCATION. Advance Care Planning: The Dietitian's Role.

PMID- 26296846
TI  - Support for community pharmacy-based alcohol interventions: a Scottish general
      public survey.
AB  - BACKGROUND: Community pharmacy teams are recognised by health agencies as vital
      to increasing capacity in the provision of public health services. Public
      awareness and support of these services in general, and relating to safe alcohol
      consumption in particular, have yet to be established. This study aimed to
      determine the Scottish general public's views regarding the role and involvement
      of community pharmacists in reducing alcohol consumption amongst customers and
      alcohol-related harm. METHODS: A cross-sectional survey of 6000 adults in
      Scotland randomly sampled from the electoral register. The piloted questionnaire
      contained items on: those health professions which could potentially advise on
      safer alcohol consumption; areas of safer alcohol consumption on which
      pharmacists could advise; attitudes towards pharmacist involvement; and
      demographics. RESULTS: Of the 1573 respondents (a 26.6% response rate), more than
      half (56.4%, 888) agreed that pharmacists could advise on safer alcohol
      consumption. Those agreeing expressed high levels of support (>=70% agreement)
      for all activities, particularly referring people to other individuals or
      organisations, discussing recommended alcohol consumption limits and how
      consumption may affect health. There was a high level of agreement of trust that
      pharmacists would discuss issues confidentially (68.7%, 1080), with a similar
      proportion (64.3%, 1011) agreeing that they would be concerned over privacy in a
      community pharmacy. CONCLUSION: Public support exists for pharmacist involvement
      in reducing alcohol consumption amongst customers and alcohol-related harm, with
      some concern over privacy. These findings warrant consideration as models of
      practice are developed and evaluated. Given the widespread availability of
      pharmacies and the ease of access to professional advice, there is potential for
      pharmacists to impact safer alcohol consumption although the efficacy of alcohol
      brief interventions remains to be demonstrated.

PMID- 26296847
TI  - Comparison of Infrared Thermal Detection Systems for mass fever screening in a
      tropical healthcare setting.
AB  - OBJECTIVES: Fever screening systems, such as Infrared Thermal Detection Systems
      (ITDS), have been used for rapid identification of potential cases during
      respiratory disease outbreaks for public health management. ITDS detect a
      difference between the subject and ambient temperature, making deployment in hot
      climates more challenging. This study, conducted in Singapore, a tropical city,
      evaluates the accuracy of three different ITDS for fever detection compared with
      traditional oral thermometry and self-reporting in a clinical setting. STUDY
      DESIGN: This study is a prospective operational evaluation conducted in the
      Singapore military on all personnel seeking medical care at a high-volume primary
      healthcare centre over a one week period in February 2014. METHODS: Three ITDS,
      the STE Infrared Fever Screening System (IFSS), the Omnisense Sentry MKIII and
      the handheld Quick Shot Infrared Thermoscope HT-F03B, were evaluated. Temperature
      measurements were taken outside the healthcare centre, under a sheltered walkway
      and compared to oral temperature. Subjects were asked if they had fever. RESULTS:
      There were 430 subjects screened, of whom 34 participants (7.9%) had confirmed
      fever, determined by oral thermometer measurement. The handheld infrared
      thermoscope had a very low sensitivity (29.4%), but a high specificity (96.8%).
      The STE ITDS had a moderate sensitivity (44.1%), but a very high specificity
      (99.1%). Self-reported fevers showed good sensitivity (88.2%) and specificity
      (93.9%). The sensitivity of the Omnisense ITDS (89.7%) was the highest among the
      three methods with good specificity (92.0%). CONCLUSION: The new generation
      Omnisense ITDS displayed a relatively high sensitivity and specificity for fever.
      Though it has a lower sensitivity, the old generation STE ITDS system showed a
      very high specificity. Self-reporting of fever was reliable. The handheld
      thermograph should not be used as a fever-screening tool under tropical
      conditions.

PMID- 26296848
TI  - Physical activity assessment for public health: efficacious use of the single
      item measure.
AB  - OBJECTIVES: The accurate mass assessment of physical activity is essential for
      effective Public Health policy and practice. Combined with a desire to minimize
      participant burden, the self-reported single-item physical activity screening
      measure has become increasingly attractive and widespread. To help reduce any
      potential misclassification, refining this instrumentation in line with any
      changes in prescribed activity levels is essential to optimize accuracy. STUDY
      DESIGN: This study compares the levels of agreement, sensitivity and specificity
      for the single-item measure versus International Physical Activity Questionnaire
      (IPAQ) using current physical activity recommendations. METHODS: Agreement was
      assessed in a non-probability sample of 7650 adults. The kappa statistic,
      sensitivity and specificity were used to assess agreement between the tools for
      classifying participants as sufficiently active for health (>=150 min of physical
      activity per week) or not, and being classified as inactive (<30 of minutes of
      physical activity per week) or not. RESULTS: The single-item measure showed weak
      agreement with the IPAQ for identifying participants who met the current physical
      activity guidelines (kappa = 0.13, 95% CI 0.12 to 0.14), sensitivity was 18.7%
      and specificity was 97.2%. For the classification of inactive participants it
      showed a moderate agreement with IPAQ (kappa = 0.45, 95% CI 0.43 to 0.47),
      sensitivity was 74.2% and specificity was 79.7%. CONCLUSIONS: The single-item
      measure had a low diagnostic capacity compared to IPAQ. Further research is
      needed if it is to be used in large scale surveys and interventions where
      screening for sufficiently active or inactive individuals is the goal.

PMID- 26296849
TI  - To screen or not to screen for adolescent idiopathic scoliosis? A review of the
      literature.
AB  - OBJECTIVES: Over the years, there has been much debate about the desirability and
      efficacy of screening for adolescent idiopathic scoliosis. To analyse the current
      evidence from a public health point of view a renewed evaluation of the
      literature was performed. STUDY DESIGN: Literature review. METHODS: We performed
      two literature searches: from January 2000 to April 2015 for systematic reviews
      or guidelines on screening for adolescent idiopathic scoliosis and from January
      2009 to April 2015 for all studies on adolescent idiopathic scoliosis and
      screening methods. We evaluated if screening for adolescent idiopathic scoliosis
      fulfils the criteria of the UK National Screenings Committee for appraising a
      screening programme. RESULTS: Adolescent idiopathic scoliosis is a condition with
      an unpredictable natural history. The optimal age and frequency of screening are
      unknown; it is not possible to predict which patients will need (conservative or
      surgical) treatment. The Forward Bending Test has a positive predictive value of
      2.6% and a sensitivity of 56% (95% CI 23-88%) for (conservative or surgical)
      treatment, and is therefore not valid enough for use in a screening programme.
      There seems to be sufficient evidence that brace treatment is effective for
      preventing progression of adolescent idiopathic scoliosis. It is not clear if
      screening is cost effective. CONCLUSIONS: Despite evidence that brace treatment
      is effective for preventing progression of adolescent idiopathic scoliosis, the
      benefits from the screening programme do not outweigh the harms. From a Public
      Health point of view, there is not enough evidence to support a screening
      programme for adolescent idiopathic scoliosis.

PMID- 26296851
TI  - Tunable Polarity Behavior and Self-Driven Photoswitching in p-WSe2/n-WS2
      Heterojunctions.
AB  - Van der Waals (vdW) p-n heterojunctions consisting of various 2D layer compounds
      are fascinating new artificial materials that can possess novel physics and
      functionalities enabling the next-generation of electronics and optoelectronics
      devices. Here, it is reported that the WSe2/WS2 p-n heterojunctions perform novel
      electrical transport properties such as distinct rectifying, ambipolar, and
      hysteresis characteristics. Intriguingly, the novel tunable polarity transition
      along a route of n-"anti-bipolar"-p-ambipolar is observed in the WSe2/WS2
      heterojunctions owing to the successive work of conducting channels of junctions,
      p-WSe2 and n-WS2 on the electrical transport of the whole systems. The type-II
      band alignment obtained from first principle calculations and built-in potential
      in this vdW heterojunction can also facilitate the efficient electron-hole
      separation, thus enabling the significant photovoltaic effect and a much enhanced
      self-driven photoswitching response in this system.

PMID- 26296850
TI  - Dark chocolate and reduced snack consumption in mildly hypertensive adults: an
      intervention study.
AB  - BACKGROUND: Several studies have shown that cocoa and cocoa-containing foods have
      the potential to lower blood pressure and improve endothelial function. Most of
      the studies reporting the beneficial effects of dark chocolate on blood pressure
      have been short (<= 4 weeks). The aim of the present 8-wks (weeks) study was to
      assess the effects of regular consumption of dark chocolate during a reduced
      snack consumption intervention on blood pressure and other cardiovascular risk
      factors in mildly hypertensive individuals. DESIGN: This was a randomized,
      controlled, cross-over trial involving 22 adults (8 women, 14 men), aged 33-64 y,
      BMI 27.7 +/- 3.7 kg/m(2) with mild hypertension. During the intervention period
      (8-wks) the participants reduced the intake of habitual snacks and replaced them
      with dark chocolate (49 g/day). In the control period, they only reduced the
      snacks without any added chocolate. Data (blood lipid profile, glucose, insulin,
      24 h blood pressure) was collected in the beginning and end of both periods
      (intervention and control), and some variables also in the run-in and run-out
      periods (weight, body fat percentage, blood pressure, arterial stiffness index,
      diet and physical activity). RESULTS: Daily consumption of dark chocolate had no
      effects on 24 h blood pressure, resting blood pressure (mean +/- SD, pre 142 +/-
      11.5/89 +/- 8.4 mmHg vs. post 142 +/- 14.2/88 +/- 9.4 mmHg in systolic and
      diastolic blood pressure, respectively) or arterial stiffness (mean +/- SD, pre
      7.68 +/- 0.88 vs. post 7.76 +/- 0.89). Weight was reduced by 1.0 +/- 2.2 kg
      during the control (reduced snack only) period, but was unchanged while eating
      chocolate (p < 0.027 between the treatments). CONCLUSION: The data collected in
      this study indicates that inclusion of dark chocolate daily in the diet had no
      significant effects on blood pressure or other cardiovascular risk factors during
      a reduced snack period. TRIAL REGISTRATION: ClinicalTrials.gov identifier
      NCT02130141.

PMID- 26296852
TI  - The First Application of the Two-Dimensional Scanning Videokymography in Excised
      Canine Larynx Model.
AB  - OBJECTIVE: Evaluation of the vibratory pattern of vocal folds is of paramount
      importance to diagnose vocal fold disorders. Currently, laryngeal videokymography
      (VKG) and digital kymography from high-speed videolaryngoscopy are the available
      techniques for studying aperiodic vibrations of vocal folds. But VKG has the
      fundamental limitation that only linear portion of the vocal fold mucosa can be
      visualized. Digital kymography has the disadvantages of no immediate feedback
      during examination, considerable waiting time before kymographic visualization,
      recoding duration limited to seconds, and extreme demands on storage space. We
      developed a new system--two-dimensional (2D) scanning VKG--for evaluation of the
      vibratory pattern of vocal folds, and the method provided a possible alternative
      with its advantages and disadvantages. Thus, we aimed to evaluate the feasibility
      of the new device for the vocal fold vibration in excised canine larynx model.
      METHODS: The vibrating pattern for vocal folds was evaluated using high-speed
      videolaryngoscopic and 2D scanning videokymographic system in the excised canine
      larynx model. RESULTS: The images of canine vocal folds were captured with high
      speed videolaryngoscopic system and converted to the kymographic images using the
      software. The kymographic image acquired by 2D scanning VKG was comparable with
      multi-line digital kymography at multiple locations. CONCLUSIONS: The vocal fold
      vibration could be evaluated in the excised canine larynx model using 2D scanning
      VKG. And this new device is expected to be a promising tool to evaluate the vocal
      fold vibration for clinical practice and voice research.

PMID- 26296853
TI  - Comparison Between Vocal Function Exercises and Voice Amplification.
AB  - PURPOSE: To compare the effectiveness of vocal function exercises (VFEs) versus
      voice amplification (VA) after a 6-week therapy for teachers diagnosed with
      behavioral dysphonia. METHODS: A total of 162 teachers with behavioral dysphonia
      were randomly allocated into two intervention groups and one control group (CG).
      Outcomes were assessed using auditory-perceptual evaluation of voice, laryngeal
      status assessment, self-ratings of the impact of dysphonia, and acoustic
      analysis. RESULTS: The VFE group showed effective changes across treatment
      outcome measures: overall severity of dysphonia relative to the CG, laryngeal
      evaluation, and self-perceived dysphonia. The VA group showed positive outcomes
      in some measures of self-rated dysphonia. The CG had poorer outcomes across self
      assessment dimensions. CONCLUSIONS: The VFE method is effective in treating the
      behavioral dysphonia of teachers, can change the overall severity and the self
      perception of the impact of dysphonia, and the laryngeal evaluation outcomes. The
      use of a voice amplifier is effective as a preventive measure because it results
      in an improved self-perception of dysphonia, especially in the work-related
      dimension. One case of dysphonia aggravation can be prevented in every three
      patients with behavioral dysphonia engaged in VFE, and one case in every five
      patients using VA. The lack of a therapeutic intervention worsens teachers'
      behavioral dysphonia in a period of 6 weeks.

PMID- 26296854
TI  - The Evolution of the Female Broadway Belt Voice: Implications for Teachers and
      Singers.
AB  - BACKGROUND: Traditionally, the female belt range extended to C5, but in current
      rock/pop Broadway productions, women are often required to belt up to an F5. This
      recent extension of the belt voice beyond C5 is a significant change, and female
      musical theater singers need effective strategies to produce these higher belt
      notes. OBJECTIVE: The intent of this study was to gain a clear understanding of
      the strategies used to successfully teach and produce the higher range of the
      female musical theater belt voice. METHODS: The study is a qualitative design
      composed of two data collection methods: interviews with four nationally
      recognized master musical theater voice teachers and 17 of their female belt
      students, and observations of the master teachers working with these students in
      their private studios. RESULTS: There was much consensus among the teachers and
      singers on the strategies of producing the higher belt range, such as
      incorporating more head voice involvement with closed vowels and maintaining a
      speech-like quality. Singers report that they produce high belt notes with more
      of a mix vocal approach. Teachers suggest that female voice type may determine
      the extent of a singer's ability in this high belt range. CONCLUSIONS: The high
      belt will be narrow, based on closed vowels, mixing in some degree of head voice
      function. Although this study has revealed some guidelines for the female musical
      theater high belt and similar strategies among master teachers, voice teachers
      should be aware of the variability of their female musical theater voice
      students.

PMID- 26296855
TI  - Accounting for sampling variability, injury under-reporting, and sensor error in
      concussion injury risk curves.
AB  - There has been recent dramatic increase in the use of sensors affixed to the
      heads or helmets of athletes to measure the biomechanics of head impacts that
      lead to concussion. The relationship between injury and linear or rotational head
      acceleration measured by such sensors can be quantified with an injury risk
      curve. The utility of the injury risk curve relies on the accuracy of both the
      clinical diagnosis and the biomechanical measure. The focus of our analysis was
      to demonstrate the influence of three sources of error on the shape and
      interpretation of concussion injury risk curves: sampling variability associated
      with a rare event, concussion under-reporting, and sensor measurement error. We
      utilized Bayesian statistical methods to generate synthetic data from previously
      published concussion injury risk curves developed using data from helmet-based
      sensors on collegiate football players and assessed the effect of the three
      sources of error on the risk relationship. Accounting for sampling variability
      adds uncertainty or width to the injury risk curve. Assuming a variety of rates
      of unreported concussions in the non-concussed group, we found that accounting
      for under-reporting lowers the rotational acceleration required for a given
      concussion risk. Lastly, after accounting for sensor error, we find strengthened
      relationships between rotational acceleration and injury risk, further lowering
      the magnitude of rotational acceleration needed for a given risk of concussion.
      As more accurate sensors are designed and more sensitive and specific clinical
      diagnostic tools are introduced, our analysis provides guidance for the future
      development of comprehensive concussion risk curves. 

PMID- 26296856
TI  - Comparison of adipose tissue- and bone marrow- derived mesenchymal stem cells for
      alleviating doxorubicin-induced cardiac dysfunction in diabetic rats.
AB  - INTRODUCTION: Doxorubicin (DOX) is a well-known anticancer drug. However its
      clinical use has been limited due to cardiotoxic effects. One of the major
      concerns with DOX therapy is its toxicity in patients who are frail, particularly
      diabetics. Several studies suggest that mesenchymal stem cells (MSCs) have the
      potential to restore cardiac function after DOX-induced injury. However, limited
      data are available on the effects of MSC therapy on DOX-induced cardiac
      dysfunction in diabetics. Our objective was to test the efficacy of bone marrow
      derived (BM-MSCs) and adipose-derived MSCs (AT-MSCs) from age-matched humans in a
      non-immune compromised rat model. METHODS: Diabetes mellitus was induced in rats
      by streptozotocin injection (STZ, 65 mg/kg b.w, i.p.). Diabetic rats were treated
      with DOX (doxorubicin hydrochloride, 2.5 mg/kg b.w, i.p) 3 times/wk for 2 weeks
      (DOX group); or with DOX+ GFP labelled BM-MSCs (2x106cells, i.v.) or with DOX +
      GFP labelled AT-MSCs (2x106cells, i.v.). Echocardiography and Langendorff
      perfusion analyses were carried out to determine the heart function.
      Immunostaining and western blot analysis of the heart tissue was carried out for
      CD31 and to assess inflammation and fibrosis. Statistical analysis was carried
      out using SPSS and data are expressed as mean +/- SD. RESULTS: Glucose levels in
      the STZ treated groups were significantly greater than control group. After 4
      weeks of intravenous injection, the presence of injected MSCs in the heart was
      confirmed through fluorescent microscopy and real time PCR for ALU transcripts.
      Both BM-MSCs and AT-MSCs injection prevented DOX-induced deterioration of %FS,
      LVDP, dp/dt max and rate pressure product. Staining for CD31 showed a significant
      increase in the number of capillaries in BM-MSCs and AT-MSCs treated animals in
      comparison to DOX treated group. Assessment of the inflammation and fibrosis
      revealed a marked reduction in the DOX-induced increase in immune cell
      infiltration, collagen deposition and alphaSMA in the BM-MSCs and AT-MSCs groups.
      CONCLUSIONS: In conclusion BM-MSCs and AT-MSCs were equally effective in
      mitigating DOX-induced cardiac damage by promoting angiogenesis, decreasing the
      infiltration of immune cells and collagen deposition.

PMID- 26296858
TI  - Prognostic Value of Coronary Computed Tomography (CT) Angiography and Coronary
      Artery Calcium Score Performed Before Revascularization.
AB  - BACKGROUND: Cardiac events after revascularization are equally attributable to
      recurrence at site of culprit lesions and development of nonculprit lesions. We
      evaluated the hypothesis that coronary computed tomography (CT) angiography and
      coronary artery calcium score (CACS) performed before revascularization predicts
      cardiac events after treatment. METHODS AND RESULTS: Among 2238 consecutive
      patients without known coronary artery disease who underwent coronary CT
      angiography and CACS, 359 patients underwent revascularization within 30 days
      after CT; in 337 of 359 (93.9%) follow-up clinical information was available. In
      addition to known cardiac risk factors, CT findings were evaluated as predictors
      of cardiac events after revascularization: CACS and the presence of CT-verified
      high-risk plaque (CT-HRP). Improvement of predictive accuracy by including CT
      findings was evaluated from a discrimination (Harrell's C-statistics) standpoint.
      During the follow-up period (median: 673, interquartile range: 47 to 1529 days),
      a total of 98 cardiac events occurred. Cox proportional hazard model revealed
      that age, diabetes, triglyceride, CACS, and nonculprit CT-HRP were significant
      predictors of overall cardiac events. Although not statistically significant,
      discriminatory power was greater for the model with CACS (C-stat: 63.2%) and the
      model with both CACS and CT-HRP (65.8%) compared to the model including neither
      CACS nor CT-HRP (60.7%). CONCLUSIONS: High CACS and the presence of nonculprit CT
      HRP performed before revascularization are significant predictors of cardiac
      events after revascularization.

PMID- 26296857
TI  - Short-Term, High-Dose Fish Oil Supplementation Increases the Production of Omega
      3 Fatty Acid-Derived Mediators in Patients With Peripheral Artery Disease (the
      OMEGA-PAD I Trial).
AB  - BACKGROUND: Patients with peripheral artery disease (PAD) experience significant
      morbidity and mortality. The OMEGA-PAD I Trial, a randomized, double-blinded,
      placebo-controlled trial, addressed the hypothesis that short-duration, high-dose
      n-3 polyunsaturated fatty acids (n-3 PUFA) oral supplementation improves
      endothelial function and inflammation in PAD. METHODS AND RESULTS: Eighty
      patients with stable claudication received 4.4 g of fish oil or placebo for 1
      month. The primary end point was endothelial function as measured by brachial
      artery flow-mediated vasodilation. Secondary end points included biomarkers of
      inflammation, n-3 polyunsaturated fatty acids metabolome changes, lipid profile,
      and walking impairment questionnaires. Although there was a significant increase
      in FMD in the fish oil group following treatment (0.7+/-1.8% increase from
      baseline, P=0.04), this response was not different then the placebo group (0.6+/
      2.5% increase from baseline, P=0.18; between-group P=0.86) leading to a negative
      finding for the primary endpoint. There was, however, a significant reduction in
      triglycerides (fish oil: -34+/-46 mg/dL, P<0.001; placebo -10+/-43 mg/dL, P=0.20;
      between-group differential P-value: 0.02), and an increase in the omega-3 index
      of 4+/-1% (P<0.001) in the fish oil group (placebo 0.1+/-0.9%, P=0.49; between
      group P<0.0001). We observed a significant increase in the production of pathway
      markers of specialized pro-resolving mediators generated from n-3 polyunsaturated
      fatty acids in the fish oil group. CONCLUSIONS: High-dose, short-duration fish
      oil supplementation did not lead to a different response in the primary end point
      of endothelial function between the treatment and placebo group, but improved
      serum triglycerides and increased the production of downstream n-3
      polyunsaturated fatty acids-derived products and mediators in patients with PAD.
      CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique
      identifier: NCT01310270.

PMID- 26296860
TI  - In vitro baselining of new pyrrolopyrimidine EGFR-TK inhibitors with Erlotinib.
AB  - Epidermal growth factor receptor tyrosine kinase inhibitors are useful in
      treatment of non-small cell lung cancer, and show promise in combination therapy
      settings. Two novel chiral pyrrolopyrimidines have been baselined towards
      Erlotinib, Lapatinib and Dasatinib using in vitro cellular studies and ADME
      profiling. One of these, (S)-2-((6-(4-(hydroxymethyl)-2-methoxyphenyl)-7H
      pyrrolo[2,3-d]pyrimidin-4-yl)amino)-2-phenylethan-1-ol, was more active than
      Erlotinib in lung and breast cancer cell models. The compound also had promising
      activity towards ovarian cancer cell lines, while low activity was seen towards
      cells of haematological origin. ADME profiling revealed good solubility, higher
      metabolic stability than Erlotinib and no inhibitory effect towards the hERG
      voltage-gated ion channel. Investigation of inhibitory potency towards 6 CYP
      isoforms generally revealed low inhibitory potency, but in the case of CYP3A4, a
      substrate dependent inhibition was noted using testosterone as substrate (IC50:
      12.5MUM). No cellular or gene toxicity was noted for the compounds or products of
      phase I metabolism. However, permeability studies using Caco-2 cells revealed a
      high efflux ratio. Further experiments using ABC transporter inhibitors revealed
      that the pyrrolopyrimidines are actively transported by the breast cancer
      resistant protein and P-glycoprotein transporters, which might prevent their
      further development into drugs. 

PMID- 26296859
TI  - Treating childhood intermittent distance exotropia: a qualitative study of
      decision making.
AB  - BACKGROUND: Engaging patients (parents/families) in treatment decisions is
      increasingly recognised as important and beneficial. Yet where the evidence base
      for treatment options is limited, as with intermittent distance exotropia (X(T)),
      this presents a challenge for families and clinicians. The purpose of this study
      was to explore how decisions are made in the management and treatment of X(T) and
      what can be done to support decision-making for clinicians, parents and children.
      METHODS: This was a qualitative study using face to face interviews with
      consultant ophthalmologists and orthoptists, and parents of children with X(T).
      Interview data were analysed using the constant comparative method. RESULTS: The
      drivers for clinicians in treatment decision-making for X(T) were the proportion
      of time the strabismus is manifest and parents' views. For parents, decisions
      were influenced by: fear of bullying and, to a lesser degree, concerns around the
      impact of the strabismus on their child's vision. Uncertainty around the
      effectiveness of treatment options caused difficulties for some clinicians when
      communicating with parents. Parental understanding of the nature of X(T) and
      rationale for treatment often differed from that of the clinicians, and this
      affected their involvement in decision-making. Though there were good examples of
      shared decision-making and parent and child engagement some parents said the
      process felt rushed and they felt excluded. Parents reported that clinicians
      provided sufficient information in consultations but they had difficulties in
      retaining verbal information to convey to other family members. CONCLUSIONS:
      Overall parents were happy with the care their child received but there is scope
      for better parent and (where appropriate) child engagement in decision-making.
      There was an expressed need for written information about X(T) to reinforce what
      was given verbally in consultations and to share with other family members.
      Access could be via the hospital website, along with videos or blogs from parents
      and children who have undergone the various management options. A method of
      assisting clinicians to explain the treatment options, together with the
      uncertainties, in a clear and concise way could be of particular benefit to
      orthoptists who have the most regular contact with parents and children, and are
      more likely to suggest conservative treatments such as occlusion and minus
      lenses.

PMID- 26296861
TI  - Influence of degassing on hot-melt extrusion process.
AB  - The present study aimed to evaluate the effect of degassing on an extrusion
      process, with respect to extrudate quality and drug release properties. Processed
      formulations were extruded with and without a degassing vent port at various
      locations along the barrel. All the experiments were performed under constant
      processing temperature, feeding rate, and screw speed. During the extrusion
      process, torque and pressure were monitored and recorded. The degassing process
      was beneficial when used over a conveying section after a mixing section. This is
      attributed to the large surface area available on the conveying elements, which
      minimizes the internal volume of the processed material, thereby facilitating the
      escape of entrapped gases. Degassing enhanced the homogeneity, physical
      appearance, and drug release properties of all the formulations. Furthermore, the
      degassing process also enhanced the cross-sectional uniformity of the extruded
      material, which is beneficial for visual monitoring during processing. Degassing
      considerably reduced the post-extrusion moisture content of Formula D3, which
      contains the highly hygroscopic polymer Kollidon(r) 17 PF, suggesting that the
      greatest influence of this process is on hygroscopic materials. The reduction in
      post-extrusion moisture content resulting from the inclusion of a degassing vent
      port, reduced fluctuations in the values of in-line monitoring parameters such as
      pressure and torque. Employing a degassing unit during hot-melt extrusion
      processing could help increase process efficacy and product quality. 

PMID- 26296862
TI  - Population pharmacokinetics of fluticasone propionate/salmeterol using two
      different dry powder inhalers.
AB  - The combination of fluticasone propionate (FLP) and salmeterol (SAL) is often
      used in clinical practice for the treatment of pulmonary disorders. The purpose
      of this study was to explore the pharmacokinetics (PK) of inhaled FLP and SAL,
      after concomitant administration, in healthy male and female subjects using two
      dry powder inhalers. Plasma concentration (C)-time (t) data were obtained from a
      single dose, two-sequence, two-period, crossover (2*2) bioequivalence (BE) study.
      Activated charcoal was co-administered in order to prohibit absorption from the
      gastrointestinal tract. A number of 60 subjects were recruited, while 57 of them
      completed the study and were included in the PK analysis. Initially, PK
      parameters of FLP and SAL were estimated using the classic non-compartmental
      methods. Subsequently, BE assessment was applied to the estimated PK parameters
      of the two dry powder inhalers. Special focus was placed on the population PK
      analysis of the C-t data, which were pooled together. 'Treatment' (i.e., test or
      reference) and 'period' of the BE study were considered as covariates. A variety
      of structural and residual error models were tested to find the one which best
      described the plasma C-t data of FLP and SAL. Demographic data were also
      evaluated for their impact on the PK parameters. Several goodness-of-fit criteria
      were utilized. The non-compartmental PK estimates of this study were in agreement
      with previously reported values. The population PK analysis showed that FLP data
      were described by a two-compartment model with first-order absorption and
      elimination kinetics. Body weight was found to affect significantly absorption
      rate constant, inter-compartmental clearance, and volume of distribution of the
      peripheral compartment. As body weight increases, the values of these PK
      parameters also rise. For SAL, the best results were obtained when a two
      compartment disposition model was used assuming very rapid absorption kinetics
      (like intravenous bolus) and first-order elimination kinetics. Gender was found
      to be a significant covariate on clearance, with men exhibiting higher clearance
      than women. 

PMID- 26296863
TI  - Phospholipid-based solid drug formulations for oral bioavailability enhancement:
      A meta-analysis.
AB  - Low bioavailability nowadays often represents a challenge in oral dosage form
      development. Solid formulations composed of drug and phospholipid (PL), which,
      upon contact with water, eventually form multilamellar liposomes (i.e.
      'proliposomes'), are an emerging approach to solve such issue. Regarded as an
      'improved' version of liposomes concerning storage stability, the potential and
      versatility of a range of such formulations for oral drug delivery have been
      extensively discussed. However, a systematic and quantitative analysis of the
      studies that applied solid PL for oral bioavailability enhancement is currently
      lacking. Such analysis is necessary for providing an overview of the research
      progress and addressing the question on how promising this approach can be on
      bioavailability enhancement. The current review performed a systematic search of
      references in three evidence-based English databases, Medline, Embase, and
      SciFinder, from the year of 1985 up till March 2015. A total of 112 research
      articles and 82 patents that involved solid PL-based formulations were
      identified. The majority of such formulations was intended for oral drug delivery
      (55%) and was developed to address low bioavailability issues (49%). A final of
      54 studies that applied such formulations for bioavailability enhancement of 43
      different drugs with poor water solubility and/or permeability were identified.
      These proof-of-concept studies with in vitro (n=31) and/or animal (n=23)
      evidences have been systematically summarized. Meta-analyses were conducted to
      measure the overall enhancement power (percent increase compared to control
      group) of solid PL formulations on drugs' solubility, permeability and oral
      bioavailability, which were found to be 127.4% (95% CI [86.1, 168.7]), 59.6% (95%
      CI [30.1, 89.0]), and 18.5% (95% CI [10.1, 26.9]) respectively. Correlations
      between the enhancement factors and in silico physiochemical properties of drugs
      were also performed to check if such approach can be used to identify the best
      candidates for oral solid PL formulation. In addition to scientific literature,
      13 solid PL formulation-related patents that addressed the issue of low oral
      bioavailability have been identified and summarized; whereas no clinical study
      was identified from the current search. By providing systematic information and
      meta-analysis on studies that applied the principle of 'proliposomes' for oral
      bioavailability enhancement, the current review should be insightful for
      formulation scientists who wish to adopt the PL based approach to overcome the
      solubility, permeability and bioavailability issues of orally delivered drugs. 

PMID- 26296864
TI  - Differential scanning calorimetry predicts the critical quality attributes of
      amorphous glibenclamide.
AB  - Selection of a crystallinity detection tool that is able to predict the critical
      quality attributes of amorphous formulations is imperative for the development of
      process control strategies. The main aim of this study was to determine the
      crystallinity detection tool that best predicts the critical quality attributes
      (i.e. physical stability and dissolution behaviour) of amorphous material.
      Glibenclamide (model drug) was milled for various durations using a planetary
      mill and characterised using Raman spectroscopy and differential scanning
      calorimetry (DSC). Physical stability studies upon storage at 60 degrees C/0% RH
      and dissolution studies (non-sink conditions) were performed on the milled
      glibenclamide samples. Different milling durations were needed to render
      glibenclamide fully amorphous according to Raman spectroscopy (60min) and onset
      of crystallisation using DSC (150min). This could be due to the superiority of
      DSC (onset of crystallisation) in detecting residual crystallinity in the samples
      milled for between 60 and 120min, which were not detectable with Raman
      spectroscopy. The physical stability upon storage and dissolution behaviour of
      the milled samples improved with increased milling duration and plateaus were
      reached after milling for certain periods of time (physical stability - 150min;
      dissolution - 120min). The residual crystallinity which was detectable with DSC
      (onset of crystallisation), but not with Raman spectroscopy, adversely affected
      the critical quality attributes of milled glibenclamide samples. In addition,
      mathematical simulations were performed on the dissolution data to determine the
      solubility advantages of the milled glibenclamide samples and to describe the
      crystallisation process that occurred during dissolution in pH7.4 phosphate
      buffer. In conclusion, the onset of crystallisation obtained from DSC
      measurements best predicts the critical quality attributes of milled
      glibenclamide samples and mathematical simulations based on the solvent-mediated
      crystallisation model were successfully performed on the dissolution data. 

PMID- 26296865
TI  - Organic cation transporter function in different in vitro models of human lung
      epithelium.
AB  - Organic cation transporters (OCT) encoded by members of the solute carrier (SLC)
      22 family of genes are involved in the disposition of physiological substrates
      and xenobiotics, including drugs used in the treatment of chronic obstructive
      lung diseases and asthma. The aim of this work was to identify continuously
      growing epithelial cell lines that closely mimic the organic cation transport of
      freshly isolated human alveolar type I-like epithelial cells (ATI) in primary
      culture, and which consequently, can be utilised as in vitro models for the study
      of organic cation transport at the air-blood barrier. OCT activity was
      investigated by measuring [(14)C]-tetraethylammonium (TEA) uptake into monolayers
      of Calu-3, NCI-H441 and A549 lung epithelial cell lines in comparison to ATI-like
      cell monolayers in primary culture. Levels of time-dependent TEA uptake were
      highest in A549 and ATI-like cells. In A549 cells, TEA uptake had a saturable and
      a non-saturable component with Km=528.5+/-373.1MUM, Vmax=0.3+/-0.1nmol/min/mg
      protein and Kd=0.02MUl/min/mg protein. TEA uptake into Calu-3 and NCI-H441 cells
      did not reach saturation within the concentration range studied. RNAi experiments
      in A549 cells confirmed that TEA uptake was mainly facilitated by OCT1 and OCT2.
      Co-incubation studies using pharmacological OCT modulators suggested that organic
      cation uptake pathways share several similarities between ATI-like primary cells
      and the NCI-H441 cell line, whereas more pronounced differences exist between
      primary cells and the A549 and Calu-3 cell lines. 

PMID- 26296866
TI  - Coning phenomena under laminar flow.
AB  - The purpose of the present study was to investigate coning phenomena in the
      paddle dissolution test under laminar flow (Reynolds number <500). The minimum
      rotation speed at which the coning phenomena disappear (no coning rpm, NCrpm) was
      measured in viscous media (23 to 147mPa?s) using various particles. The exponent
      values of particle size, density, and viscosity parameters in the Zwietering
      equation were found to be 0.066, 0.38, and 0.22, respectively. NCrpm was
      appropriately predicted by the Zwietering equation (average error: 8rpm). These
      values are very different from those for turbulent flow, suggesting that the main
      physical forces governing the motion of particles can be different between
      turbulent flow and laminar flow. This point should be taken into account when
      understanding the dissolution of drug products in viscous fluids representing the
      fed state. 

PMID- 26296867
TI  - Fructosamine is a risk factor for myocardial infarction and all-cause mortality -
      Longitudinal experience from the AMORIS cohort.
AB  - BACKGROUND AND AIMS: Glycation is linked to microvascular complications of
      diabetes and also to macrovascular events. Fructosamine is a biomarker of
      glycation but its associations to macrovascular complications are not well
      documented. The aim of this study was to evaluate fructosamine as a predictor of
      myocardial infarction and all-cause mortality in a large population based cohort.
      METHODS AND RESULTS: Information on glucose and fructosamine was obtained from
      subjects of the AMORIS cohort (n = 338,443) followed for 19 years on average.
      Incident cases of myocardial infarction and death from any cause were identified
      from national patient and cause of death register respectively. The incidence of
      myocardial infarction (n = 21,526 cases) and all-cause mortality (n = 73,458
      deaths) increased at a fructosamine of 2.30 mmol/L or above. For myocardial
      infarction, the sex-age- fasting- and entry period adjusted hazard ratio in
      subjects above 2.70 mmol/L vs. reference range subjects was 2.88 (95% CI: 2.70
      3.07). The corresponding hazard ratio for all-cause mortality was 2.31 (95% CI:
      2.21-2.41). These associations remained basically unchanged after adjustment for
      total cholesterol, triglycerides, albumin, social class, smoking and
      hypertension. When additional adjustment for glucose was performed the
      associations were attenuated but remained. In a sub cohort with simultaneous
      measurements of fructosamine, HbA1c and fasting glucose respectively similar
      associations were observed (n = 9746). CONCLUSION: There is a strong association
      between fructosamine and myocardial infarction and death from any cause when
      major cardiovascular risk factors are accounted for. In addition, this
      association could only partly be explained by glucose levels.

PMID- 26296868
TI  - Renin-angiotensin-aldosterone-system blockade and development of chronic kidney
      disease.

PMID- 26296869
TI  - Difference in blood pressure between early and late menopausal transition was
      significant in healthy Korean women.
AB  - BACKGROUND: Although the prevalence of hypertension is higher in postmenopausal
      women than in premenopausal women, little is known about changes in blood
      pressure (BP) during the menopausal transition. We evaluated BP according to the
      menopausal transition and associated factors in healthy Korean women. METHODS:
      This cross-sectional study involved 2037 women aged 44 to 56 years who presented
      at a health-screening center in Seoul, Korea, from November 2012 to March 2013.
      The association between BP and menopausal transition and the risk factors related
      to elevated BP were determined using multiple linear regression analyses.
      Menopausal status was divided by four groups as premenopause, early menopausal
      transition, late menopausal transition and postmenopause. RESULTS: Both systolic
      and diastolic blood pressure (SBP and DBP) differed significantly according to
      the menopausal status. BP showed the greatest difference between early and late
      menopausal transition. After adjusting for variables related to hypertension, SBP
      (beta = 2.753, p < 0.01) and DBP (beta = 1.746, p = 0.02) were significantly
      higher in late than early menopausal transition. The prevalence of hypertension
      was significantly different between early and late menopausal transition (1.4 vs.
      6.1 %). Waist circumference, glucose, and triglycerides were positively and
      significantly associated with SBP and DBP during menopause. CONCLUSIONS: BP and
      the prevalence of hypertension were significantly associated with period between
      early and late menopausal transition, suggesting that changes in BP during the
      menopausal transition are significant. Therefore, frequent monitoring will be
      needed for early detection of hypertension during the menopausal transition.

PMID- 26296870
TI  - Impact of localisation of deep brain stimulation electrodes on motor and
      neurobehavioural outcomes in Parkinson's disease.
AB  - BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN)
      represents a well-established treatment in advanced Parkinson's disease (PD) for
      motor signs, but it is still debated concerning psychiatric effects. OBJECTIVE:
      Exploration of relation between position of active electrode contacts and
      neuropsychological and motor change after STN DBS procedure for PD. METHODS: A
      cohort of 34 patients who underwent STN DBS was followed for 6 months.
      Preoperative and postoperative assessments included mood evaluation (depression
      and mania) and motor status. Active contact localisation was identified regarding
      position into the STN (4 groups: IN meant contacts were IN-IN IN-BORDER; OUT: OUT
      OUT or OUT-BORDER; BORDER: BORDER-BORDER; IN-OUT: IN-OUT) and compared with
      clinical outcomes. RESULTS: STN DBS significantly improved motor scores and
      reduced dopaminergic medication when compared with baseline and active lead
      groups: the best result was seen with the IN group. At 3 and 6 months
      postsurgery, depression and manic scores do not significantly differ compared
      with baseline and between leads groups. Focusing on symptom domains and compared
      with baseline, a significant loss of appetite was observed for the IN group at M3
      and a significant increase in appetite from baseline was observed at M3 for the
      OUT group. Graphic representations illustrate that postsurgery evolution
      parameters at M3 or M6 are very good discriminant variables and well
      differentiate all leading groups. CONCLUSIONS: Stimulation of zona incerta may
      influence appetite and weight gain. Our clinical results seem to support a
      personalised DBS-targeted Parkinson therapy including individual motor and non
      motor parameters.

PMID- 26296871
TI  - Neurofilaments in the diagnosis of motoneuron diseases: a prospective study on
      455 patients.
AB  - OBJECTIVES: Biomarkers for the diagnosis of motoneuron diseases (MND) are
      urgently needed to improve the diagnostic pathway, patient stratification and
      monitoring. The aim of this study was to validate candidate markers for MND in
      cerebrospinal fluid (CSF) and specify cut-offs based on large patient cohorts by
      especially considering patients who were seen under the initial differential
      diagnosis (MND mimics). METHODS: In a prospective study, we investigated CSF of
      455 patients for neurofilament light chain (NfL), phosphorylated heavy chain
      (pNfH), tau protein (Tau) and phospho-tau protein (pTau). Analysed cohorts
      included patients with apparently sporadic and familial amyotrophic lateral
      sclerosis (ALS) and primary lateral sclerosis (PLS) (MND, n=253), MND mimics
      (n=85) and neurological control groups. Cut-off values were specified, and
      diagnostic performance and correlation with progression were analysed. RESULTS:
      Nfs were significantly higher in the MND group compared to the control groups,
      whereas Tau and pTau did not differ. At a cut-off level of 2200 pg/mL for NfL, a
      77% diagnostic sensitivity (CI 71% to 82%), 85% specificity (CI 79% to 90%) and
      87% positive predictive value (PPV) (CI 81% to 91%) were achieved. For pNfH, we
      calculated 83% sensitivity (CI 78% to 88%), 77% specificity (CI 71% to 83%) and
      82% PPV (CI 77% to 86%) at 560 pg/mL. There were no significant differences
      between sporadic and genetic ALS or PLS. Nf levels were elevated at early disease
      stage, and correlated moderately with MND progression and duration. CONCLUSIONS:
      Neurofilaments in CSF have a high relevance for the differential diagnosis of
      MNDs and should be included in the diagnostic work-up of patients. Their value as
      prognostic markers should be investigated further.

PMID- 26296872
TI  - C/D box sRNA-guided 2'-O-methylation patterns of archaeal rRNA molecules.
AB  - BACKGROUND: In archaea and eukaryotes, ribonucleoprotein complexes containing
      small C/D box s(no)RNAs use base pair complementarity to target specific sites
      within ribosomal RNA for 2'-O-ribose methylation. These modifications aid in the
      folding and stabilization of nascent rRNA molecules and their assembly into
      ribosomal particles. The genomes of hyperthermophilic archaea encode large
      numbers of C/D box sRNA genes, suggesting an increased necessity for rRNA
      stabilization at extreme growth temperatures. RESULTS: We have identified the
      complete sets of C/D box sRNAs from seven archaea using RNA-Seq methodology. In
      total, 489 C/D box sRNAs were identified, each containing two guide regions. A
      combination of computational and manual analyses predicts 719 guide interactions
      with 16S and 23S rRNA molecules. This first pan-archaeal description of guide
      sequences identifies (i) modified rRNA nucleotides that are frequently conserved
      between species and (ii) regions within rRNA that are hotspots for 2'-O
      methylation. Gene duplication, rearrangement, mutational drift and convergent
      evolution of sRNA genes and guide sequences were observed. In addition, several
      C/D box sRNAs were identified that use their two guides to target locations
      distant in the rRNA sequence but close in the secondary and tertiary structure.
      We propose that they act as RNA chaperones and facilitate complex folding events
      between distant sequences. CONCLUSIONS: This pan-archaeal analysis of C/D box
      sRNA guide regions identified conserved patterns of rRNA 2'-O-methylation in
      archaea. The interaction between the sRNP complexes and the nascent rRNA
      facilitates proper folding and the methyl modifications stabilize higher order
      rRNA structure within the assembled ribosome.

PMID- 26296874
TI  - Streptomyces olivicoloratus sp. nov., an antibiotic-producing bacterium isolated
      from soil.
AB  - Strain T13T, isolated from forest soil in Jeollabuk-do, South Korea, exhibited
      antibiotic production on yeast extract-malt extract-glucose (YMG) medium
      containing magnesium chloride as a trace mineral, and inhibited the growth of
      Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa, Staphylococcus
      epidermidis, Paenibacillus larvae, Escherichia coli, Candida albicans and
      Aspergillus niger. Growth occurred at 15-45  degrees C, pH 4-11 and in the
      presence of up to 2 % (w/v) NaCl. Biochemical analyses indicated that the
      predominant menaquinones produced by this strain were MK-9(H6) and MK-9(H8);
      small amounts of MK-10(H2) and MK-10(H4) were also detected. The polar lipid
      profile comprised diphosphatidylglycerol, phosphatidylethanolamine and
      phosphatidylcholine, and the cell-wall peptidoglycan contained ll-diaminopimelic
      acid, glutamic acid, alanine and glycine. Whole-cell hydrolysates contained
      glucose, galactose, ribose and rhamnose. The fatty-acid profile of strain T13T
      was made up predominantly of iso- and anteiso-branched fatty acids. Genetic
      analyses demonstrated that strain T13T is closely related to Streptomyces
      gramineus JR-43T (98.29 % 16S rRNA gene sequence similarity), S. graminisoli JR
      19T (97.99 %), S. rhizophilus JR-41T (97.86 %), S. longwoodensis LMG 20096T
      (97.84 %), S. graminifolii JL-22T (97.79 %) and S. yaanensis Z4T (97.56 %), and
      DNA-DNA hybridization yielded relatedness values of 35.27-43.42 % when T13T was
      compared to related strains. The results of morphological, chemotaxonomic,
      phylogenetic and phenotypic analyses confirm that this strain represents a novel
      species of the genus Streptomyces, for which the name Streptomyces olivicoloratus
      sp. nov. is proposed. The type strain is T13T ( = KEMB 9005-210T = KACC 18227T =
      NBRC 110901T). 

PMID- 26296873
TI  - Naproxcinod shows significant advantages over naproxen in the mdx model of
      Duchenne Muscular Dystrophy.
AB  - BACKGROUND: In dystrophin-deficient muscles of Duchenne Muscular Dystrophy (DMD)
      patients and the mdx mouse model, nitric oxide (NO) signalling is impaired.
      Previous studies have shown that NO-donating drugs are beneficial in dystrophic
      mouse models. Recently, a long-term treatment (9 months) of mdx mice with
      naproxcinod, an NO-donating naproxen, has shown a significant improvement of the
      dystrophic phenotype with beneficial effects present throughout the disease
      progression. It remains however to be clearly dissected out which specific
      effects are due to the NO component compared with the anti-inflammatory activity
      associated with naproxen. Understanding the contribution of NO vs the anti
      inflammatory effect is important, in view of the potential therapeutic
      perspective, and this is the final aim of this study. METHODS: Five-week-old mdx
      mice received either naproxcinod (30 mg/kg) or the equimolar dose of naproxen (20
      mg/kg) in the diet for 6 months. Control mdx mice were used as reference.
      Treatments (or vehicle for control groups) were administered daily in the diet.
      For the first 3 months the study was performed in sedentary animals, then all
      mice were subjected to exercise until the sixth month. Skeletal muscle force was
      assessed by measuring whole body tension in sedentary animals as well as in
      exercised mice and resistance to fatigue was measured after 3 months of running
      exercise. At the end of 6 months of treatment, animals were sacrificed for
      histological analysis and measurement of naproxen levels in blood and skeletal
      muscle. RESULTS: Naproxcinod significantly ameliorated skeletal muscle force and
      resistance to fatigue in sedentary as well as in exercised mice, reduced
      inflammatory infiltrates and fibrosis deposition in both cardiac and diaphragm
      muscles. Conversely, the equimolar dose of naproxen showed no effects on fibrosis
      and improved muscle function only in sedentary mice, while the beneficial effects
      in exercised mice were lost demonstrating a limited and short-term effect.
      CONCLUSION: In conclusion, this study shows that NO donation may have an
      important role, in addition to anti-inflammatory activity, in slowing down the
      progression of the disease in the mdx mouse model therefore positioning
      naproxcinod as a promising candidate for treatment of DMD.

PMID- 26296875
TI  - Phylogenomic analysis shows that 'Bacillus vanillea' is a later heterotypic
      synonym of Bacillus siamensis.
AB  - 'Bacillus vanillea' XY18 ( = CGMCC 8629 = NCCB 100507) was isolated from cured
      vanilla beans and involved in the formation of vanilla aroma compounds. A draft
      genome of this strain was assembled and yielded a length of 3.71 Mbp with a DNA
      G+C content of 46.3 mol%. Comparative genomic analysis with its nearest relatives
      showed only minor differences between this strain and the genome of the Bacillus
      siamensis KCTC 13613T ( = BCC 22614T = KACC 16244T), with a calculated DNA-DNA
      hybridization (DDH) value of 91.2 % and an average nucleotide identity (ANI) of
      98.9 %. This DDH value is well above the recommended 70 % threshold for species
      delineation, as well as the ANI threshold of 95 %. In addition, the results of
      morphological, physiological, chemotaxonomic and phylogenetic analyses indicate
      that the type strains of these two taxa are highly similar with phenotype
      coherence. A core genome multi-locus sequencing analysis was conducted for the
      strains and the results show that 'Bacillus vanillea' XY18 clusters closely to
      the type strain of Bacillus siamensis. Therefore, it is proposed that the species
      'Bacillus vanillea' XY18 ( = CGMCC 8629 = NCCB 100507) should be reclassified as
      a later heterotypic synonym of Bacillus siamensis KCTC 13613T ( = BCC 22614T =
      KACC 16244T). An emended description of Bacillus siamensis is provided.

PMID- 26296876
TI  - Roles of Agrobacterium tumefaciens C58 ZntA and ZntB and the transcriptional
      regulator ZntR in controlling Cd2+/Zn2+/Co2+ resistance and the peroxide stress
      response.
AB  - The putative zinc exporters ZntA (a P1B-type ATPase) and ZntB (2-TM-GxN family)
      in Agrobacterium tumefaciens were characterized. The expression of the zntA gene
      is inducible by CdCl2, ZnCl2 and CoCl2, of which CdCl2 is the most potent
      inducer, whereas zntB is constitutively expressed. The metal-induced expression
      of zntA is controlled by the MerR-like regulator ZntR. The zntA and zntR mutants
      were highly sensitive to CdCl2 and ZnCl2, and CoCl2 sensitivity was demonstrated
      to a lesser extent. By contrast, the zntB mutant showed similar levels of metal
      resistance to the WT strain. Even in the zntA mutant background, zntB did not
      play an apparent role in metal resistance under the conditions tested. The
      inactivation of zntA increased the accumulation of intracellular cadmium and
      zinc, and conferred hyper-resistance to H2O2. Thus, the metal transporter ZntA
      and its regulator ZntR are important for controlling zinc homeostasis and cadmium
      and cobalt detoxification. The loss of either the zntA or zntR gene did not
      affect the virulence of A. tumefaciens in Nicotiana benthamiana. 

PMID- 26296877
TI  - Letter to the Editor regarding "Tonsillectomy versus Tonsillotomy: A Study of
      Parental Preference".

PMID- 26296878
TI  - Heterozygous deletion at the SOX10 gene locus in two patients from a Chinese
      family with Waardenburg syndrome type II.
AB  - OBJECTIVES: Waardenburg syndrome (WS) is a rare disease characterized by
      sensorineural deafness and pigment disturbance. To date, almost 100 mutations
      have been reported, but few reports on cases with SOX10 gene deletion. The
      inheritance pattern of SOX10 gene deletion is still unclear. Our objective was to
      identify the genetic causes of Waardenburg syndrome type II in a two-generation
      Chinese family. METHODS: Clinical evaluations were conducted in both of the
      patients. Microarray analysis and multiplex ligation-dependent probe
      amplification (MLPA) were performed to identify disease-related copy number
      variants (CNVs). DNA sequencing of the SOX10, MITF and SNAI2 genes was performed
      to identify the pathogenic mutation responsible for WS2. RESULTS: A 280kb
      heterozygous deletion at the 22q13.1 chromosome region (including SOX10) was
      detected in both of the patients. No mutation was found in the patients,
      unaffected family members and 30 unrelated healthy controls. CONCLUSIONS: This
      report is the first to describe SOX10 heterozygous deletions in Chinese WS2
      patients. Our result conform the thesis that heterozygous deletions at SOX10 is
      an important pathogenicity for WS, and present as autosomal dominant inheritance.
      Nevertheless, heterozygous deletion of the SOX10 gene would be worth
      investigating to understand their functions and contributions to neurologic
      phenotypes.

PMID- 26296879
TI  - Prevalence and referral rates in neonatal hearing screening program using two
      step hearing screening protocol in Chennai - A prospective study.
AB  - OBJECTIVE: To estimate the prevalence and referral rates in well born and high
      risk babies using two step hearing screening protocol with Distortion Product
      Otoacoustic Emissions (DPOAE) and Automated Auditory Brainstem Response (AABR).
      METHOD: A prospective study was carried out on 1405 neonates (983 well born
      babies and 422 high risk babies) who were screened during May 2013 to January
      2015 at Institute of Obstetrics and Gynecology, Madras Medical College, Chennai.
      All neonates were screened using two step screening protocol. They were initially
      tested with DPOAE. Referred babies in DPOAE were screened with AABR subsequently.
      RESULTS: Among 1405 (100%) neonates 983 (69.96%) were well born babies and 422
      (30.03%) were high risk babies. Total referral rate in DPOAE was found to be 311
      (22.13%) among which 195 (13.87%) were well born babies and 116 (8.25%) were high
      risk babies. Out of 311 babies 31 (2.20%) babies were referred in AABR screening.
      In 31 babies referred in AABR 11(0.78%) were from well born group and 20 (1.42%)
      were from the high risk group. Further diagnostic evaluation of these babies, 2
      (0.14%) were confirmed to have hearing loss. This study reveals, the prevalence
      of congenital hearing loss in our population is 1.42 per 1000 babies. CONCLUSION:
      Using two step protocol especially AABR along with DPOAE at the initial level of
      testing significantly reduces referral rates in new born screening programs. Also
      AABR decreases the false positive responses hence increasing the efficiency of
      screening program.

PMID- 26296880
TI  - An in vitro and in vivo study on the synergistic effect and mechanism of
      itraconazole or voriconazole alone and in combination with tetrandrine against
      Aspergillus fumigatus.
AB  - In this study, we investigated the in vitro antifungal effects of
      itraconazole/voriconazole (ITR/VRC) alone and in combination with tetrandrine
      (TET) against 23 clinical isolates of A. fumigatus using a chequerboard
      microdilution method. The dynamic antifungal effects of TET with ITR/VRC against
      A. fumigatus were assessed in vivo using time-kill curves following systemic
      infection of mice with A. fumigatus. After treatment, efflux pump activity was
      determined by the efflux of rhodamine 6G (R6G). When ITR was combined with TET,
      ITR MICs were reduced from 0.125-32 to 0.0625-2 MUg ml(-1), and TET MICs were
      reduced from 256-512 to 8-64 MUg ml(-1). When VRC was combined with TET, VRC MICs
      were reduced from 0.125-2 to 0.03125-0.5 MUg ml(-1), and TET MICs were reduced
      from 256-512 to 8-256 MUg ml(-1). Time-kill curves revealed that A. fumigatus
      viability was reduced after treatment with ITR/VRC combined with TET versus
      ITR/VRC alone. ITR/VRC combined with TET significantly prolonged mouse survival
      and reduced kidney and brain tissue burdens versus ITR/VRC alone (P < 0.05).
      Moreover, TET inhibited R6G efflux of A. fumigatus. Thus, in vitro and in vivo,
      TET acted synergistically with ITR/VRC against A. fumigatus, and the synergistic
      mechanism was related to inhibition of the drug efflux pump.

PMID- 26296881
TI  - Identification of a novel cell culture adaptation site on the capsid of foot-and
      mouth disease virus.
AB  - Vaccination remains the most effective tool for control of foot-and-mouth disease
      both in endemic countries and as an emergency preparedness for new outbreaks.
      Foot-and-mouth disease vaccines are chemically inactivated virus preparations and
      the production of new vaccines is critically dependent upon cell culture
      adaptation of field viruses, which can prove problematic. A major driver of cell
      culture adaptation is receptor availability. Field isolates of foot-and-mouth
      disease virus (FMDV) use RGD-dependent integrins as receptors, whereas cell
      culture adaptation often selects for variants with altered receptor preferences.
      Previously, two independent sites on the capsid have been identified where
      mutations are associated with improved cell culture growth. One is a shallow
      depression formed by the three major structural proteins (VP1-VP3) where
      mutations create a heparan sulphate (HS)-binding site (the canonical HS-binding
      site). The other involves residues of VP1 and is located at the fivefold symmetry
      axis. For some viruses, changes at this site result in HS binding; for others,
      the receptors are unknown. Here, we report the identification of a novel site on
      VP2 where mutations resulted in an expanded cell tropism of a vaccine variant of
      A/IRN/87 (called A - ). Furthermore, we show that introducing the same mutations
      into a different type A field virus (A/TUR/2/2006) resulted in the same expanded
      cell culture tropism as the A/IRN/87 A -  vaccine variant. These observations add
      to the evidence for multiple cell attachment mechanisms for FMDV and may be
      useful for vaccine manufacture when cell culture adaptation proves difficult. 

PMID- 26296882
TI  - Brain-expressed X-linked 2 Is Pivotal for Hyperactive Mechanistic Target of
      Rapamycin (mTOR)-mediated Tumorigenesis.
AB  - Frequent alteration of upstream proto-oncogenes and tumor suppressor genes
      activates mechanistic target of rapamycin (mTOR) and causes cancer. However, the
      downstream effectors of mTOR remain largely elusive. Here we report that brain
      expressed X-linked 2 (BEX2) is a novel downstream effector of mTOR. Elevated BEX2
      in Tsc2(-/-) mouse embryonic fibroblasts, Pten(-/-) mouse embryonic fibroblasts,
      Tsc2-deficient rat uterine leiomyoma cells, and brains of neuronal specific Tsc1
      knock-out mice were abolished by mTOR inhibitor rapamycin. Furthermore, BEX2 was
      also increased in the liver of a hepatic specific Pten knock-out mouse and the
      kidneys of Tsc2 heterozygous deletion mice, and a patient with tuberous sclerosis
      complex (TSC). mTOR up-regulation of BEX2 was mediated in parallel by both STAT3
      and NF-kappaB. BEX2 was involved in mTOR up-regulation of VEGF production and
      angiogenesis. Depletion of BEX2 blunted the tumorigenesis of cells with activated
      mTOR. Therefore, enhanced STAT3/NF-kappaB-BEX2-VEGF signaling pathway contributes
      to hyperactive mTOR-induced tumorigenesis. BEX2 may be targeted for the treatment
      of the cancers with aberrantly activated mTOR signaling pathway. 

PMID- 26296883
TI  - X-ray Structural and Functional Studies of the Three Tandemly Linked Domains of
      Non-structural Protein 3 (nsp3) from Murine Hepatitis Virus Reveal Conserved
      Functions.
AB  - Murine hepatitis virus (MHV) has long served as a model system for the study of
      coronaviruses. Non-structural protein 3 (nsp3) is the largest nsp in the
      coronavirus genome, and it contains multiple functional domains that are required
      for coronavirus replication. Despite the numerous functional studies on MHV and
      its nsp3 domain, the structure of only one domain in nsp3, the small ubiquitin
      like domain 1 (Ubl1), has been determined. We report here the x-ray structure of
      three tandemly linked domains of MHV nsp3, including the papain-like protease 2
      (PLP2) catalytic domain, the ubiquitin-like domain 2 (Ubl2), and a third domain
      that we call the DPUP (domain preceding Ubl2 and PLP2) domain. DPUP has close
      structural similarity to the severe acute respiratory syndrome coronavirus unique
      domain C (SUD-C), suggesting that this domain may not be unique to the severe
      acute respiratory syndrome coronavirus. The PLP2 catalytic domain was found to
      have both deubiquitinating and deISGylating isopeptidase activities in addition
      to proteolytic activity. A computationally derived model of MHV PLP2 bound to
      ubiquitin was generated, and the potential interactions between ubiquitin and
      PLP2 were probed by site-directed mutagenesis. These studies extend substantially
      our structural knowledge of MHV nsp3, providing a platform for further
      investigation of the role of nsp3 domains in MHV viral replication. 

PMID- 26296884
TI  - Striking Oxygen Sensitivity of the Peptidylglycine alpha-Amidating Monooxygenase
      (PAM) in Neuroendocrine Cells.
AB  - Interactions between biological pathways and molecular oxygen require robust
      mechanisms for detecting and responding to changes in cellular oxygen
      availability, to support oxygen homeostasis. Peptidylglycine alpha-amidating
      monooxygenase (PAM) catalyzes a two-step reaction resulting in the C-terminal
      amidation of peptides, a process important for their stability and biological
      activity. Here we show that in human, mouse, and insect cells, peptide amidation
      is exquisitely sensitive to hypoxia. Different amidation events on chromogranin
      A, and on peptides processed from proopiomelanocortin, manifest similar striking
      sensitivity to hypoxia in a range of neuroendocrine cells, being progressively
      inhibited from mild (7% O2) to severe (1% O2) hypoxia. In developing Drosophila
      melanogaster larvae, FMRF amidation in thoracic ventral (Tv) neurons is
      strikingly suppressed by hypoxia. Our findings have thus defined a novel
      monooxygenase-based oxygen sensing mechanism that has the capacity to signal
      changes in oxygen availability to peptidergic pathways.

PMID- 26296885
TI  - Intestine-specific Disruption of Hypoxia-inducible Factor (HIF)-2alpha Improves
      Anemia in Sickle Cell Disease.
AB  - Sickle cell disease (SCD) is caused by genetic defects in the beta-globin chain.
      SCD is a frequently inherited blood disorder, and sickle cell anemia is a common
      type of hemoglobinopathy. During anemia, the hypoxic response via the
      transcription factor hypoxia-inducible factor (HIF)-2alpha is highly activated in
      the intestine and is essential in iron absorption. Intestinal disruption of HIF
      2alpha protects against tissue iron accumulation in iron overload anemias.
      However, the role of intestinal HIF-2alpha in regulating anemia in SCD is
      currently not known. Here we show that in mouse models of SCD, disruption of
      intestinal HIF-2alpha significantly decreased tissue iron accumulation. This was
      attributed to a decrease in intestinal iron absorptive genes, which were highly
      induced in a mouse model of SCD. Interestingly, disruption of intestinal HIF
      2alpha led to a robust improvement in anemia with an increase in RBC, hemoglobin,
      and hematocrit. This was attributed to improvement in RBC survival, hemolysis,
      and insufficient erythropoiesis, which is evident from a significant decrease in
      serum bilirubin, reticulocyte counts, and serum erythropoietin following
      intestinal HIF-2alpha disruption. These data suggest that targeting intestinal
      HIF-2alpha has a significant therapeutic potential in SCD pathophysiology. 

PMID- 26296886
TI  - Protein N-terminal Acetylation by the NatA Complex Is Critical for Selective
      Mitochondrial Degradation.
AB  - Mitophagy is an evolutionarily conserved autophagy pathway that selectively
      degrades mitochondria. Although it is well established that this degradation
      system contributes to mitochondrial quality and quantity control, mechanisms
      underlying mitophagy remain largely unknown. Here, we report that protein N
      terminal acetyltransferase A (NatA), an enzymatic complex composed of the
      catalytic subunit Ard1 and the adaptor subunit Nat1, is crucial for mitophagy in
      yeast. NatA is associated with the ribosome via Nat1 and acetylates the second
      amino acid residues of nascent polypeptides. Mitophagy, but not bulk autophagy,
      is strongly suppressed in cells lacking Ard1, Nat1, or both proteins. In
      addition, loss of NatA enzymatic activity causes impairment of mitochondrial
      degradation, suggesting that protein N-terminal acetylation by NatA is important
      for mitophagy. Ard1 and Nat1 mutants exhibited defects in induction of Atg32, a
      protein essential for mitophagy, and formation of mitochondria-specific
      autophagosomes. Notably, overexpression of Atg32 partially recovered mitophagy in
      NatA-null cells, implying that this acetyltransferase participates in mitophagy
      at least in part via Atg32 induction. Together, our data implicate NatA-mediated
      protein modification as an early regulatory step crucial for efficient mitophagy.

PMID- 26296887
TI  - Lipin1 Regulates Skeletal Muscle Differentiation through Extracellular Signal
      regulated Kinase (ERK) Activation and Cyclin D Complex-regulated Cell Cycle
      Withdrawal.
AB  - Lipin1, an intracellular protein, plays critical roles in controlling lipid
      synthesis and energy metabolism through its enzymatic activity and nuclear
      transcriptional functions. Several mouse models of skeletal muscle wasting are
      associated with lipin1 mutation or altered expression. Recent human studies have
      suggested that children with homozygous null mutations in the LPIN1 gene suffer
      from rhabdomyolysis. However, the underlying pathophysiologic mechanism is still
      poorly understood. In the present study we examined whether lipin1 contributes to
      regulating muscle regeneration. We characterized the time course of skeletal
      muscle regeneration in lipin1-deficient fld mice after injury. We found that fld
      mice exhibited smaller regenerated muscle fiber cross-sectional areas compared
      with wild-type mice in response to injury. Our results from a series of in vitro
      experiments suggest that lipin1 is up-regulated and translocated to the nucleus
      during myoblast differentiation and plays a key role in myogenesis by regulating
      the cytosolic activation of ERK1/2 to form a complex and a downstream effector
      cyclin D3-mediated cell cycle withdrawal. Overall, our study reveals a previously
      unknown role of lipin1 in skeletal muscle regeneration and expands our
      understanding of the cellular and molecular mechanisms underlying skeletal muscle
      regeneration. 

PMID- 26296888
TI  - Selective Irreversible Inhibition of Neuronal and Inducible Nitric-oxide Synthase
      in the Combined Presence of Hydrogen Sulfide and Nitric Oxide.
AB  - Citrulline formation by both human neuronal nitric-oxide synthase (nNOS) and
      mouse macrophage inducible NOS was inhibited by the hydrogen sulfide (H2S) donor
      Na2S with IC50 values of ~2.4.10(-5) and ~7.9.10(-5) m, respectively, whereas
      human endothelial NOS was hardly affected at all. Inhibition of nNOS was not
      affected by the concentrations of l-arginine (Arg), NADPH, FAD, FMN,
      tetrahydrobiopterin (BH4), and calmodulin, indicating that H2S does not interfere
      with substrate or cofactor binding. The IC50 decreased to ~1.5.10(-5) m at pH 6.0
      and increased to ~8.3.10(-5) m at pH 8.0. Preincubation of concentrated nNOS with
      H2S under turnover conditions decreased activity after dilution by ~70%,
      suggesting irreversible inhibition. However, when calmodulin was omitted during
      preincubation, activity was not affected, suggesting that irreversible inhibition
      requires both H2S and NO. Likewise, NADPH oxidation was inhibited with an IC50 of
      ~1.9.10(-5) m in the presence of Arg and BH4 but exhibited much higher IC50
      values (~1.0-6.1.10(-4) m) when Arg and/or BH4 was omitted. Moreover, the
      relatively weak inhibition of nNOS by Na2S in the absence of Arg and/or BH4 was
      markedly potentiated by the NO donor 1-(hydroxy-NNO-azoxy)-l-proline, disodium
      salt (IC50 ~ 1.3-2.0.10(-5) m). These results suggest that nNOS and inducible NOS
      but not endothelial NOS are irreversibly inhibited by H2S/NO at modest
      concentrations of H2S in a reaction that may allow feedback inhibition of NO
      production under conditions of excessive NO/H2S formation.

PMID- 26296889
TI  - Role of Erk1/2 signaling in the regulation of neutrophil versus monocyte
      development in response to G-CSF and M-CSF.
AB  - Lineage specification in the hematopoietic system depends on the expression of
      lineage specific transcription factors. However, the role of hematopoietic
      cytokines in this process has been controversial and little is known about the
      intracellular signaling mechanisms by which cytokines instruct lineage choice. G
      CSF and M-CSF are two lineage-specific cytokines that play a dominant role in
      granulopoiesis and monopoiesis, respectively. We show here that a G-CSFR mutant
      in which tyrosine 729 had been mutated to phenylalanine (Y729F) promoted monocyte
      rather than neutrophil development in myeloid precursors, which was associated
      with prolonged activation of Erk1/2 and augmented activation of downstream
      targets c-Fos and Egr1. Inhibition of Erk1/2 activation or knockdown of c-Fos or
      Egr1 largely rescued neutrophil development in cells expressing G-CSFR Y729F. We
      also show that M-CSF, but not G-CSF, stimulated strong and sustained activation
      of Erk1/2 in mouse lineage marker negative (Lin(-)) bone marrow cells.
      Significantly, inhibition of Erk1/2 signaling in these cells favored neutrophil
      over monocyte development in response to M-CSF. Thus, prolonged Erk1/2 activation
      resulted in monocyte development following G-CSF induction whereas inhibition of
      Erk1/2 signaling promoted neutrophil development at the expense of monocyte
      formation in response to M-CSF. These results reveal an important mechanism by
      which G-CSF and M-CSF instruct neutrophil versus monocyte lineage choice, i.e.
      differential activation of Erk1/2 pathway. 

PMID- 26296890
TI  - Amyloid Precursor Protein (APP) Metabolites APP Intracellular Fragment (AICD),
      Abeta42, and Tau in Nuclear Roles.
AB  - Amyloid precursor protein (APP) metabolites (amyloid-beta (Abeta) peptides) and
      Tau are the main components of senile plaques and neurofibrillary tangles, the
      two histopathological hallmarks of Alzheimer disease. Consequently, intense
      research has focused upon deciphering their physiological roles to understand
      their altered state in Alzheimer disease pathophysiology. Recently, the impact of
      APP metabolites (APP intracellular fragment (AICD) and Abeta) and Tau on the
      nucleus has emerged as an important, new topic. Here we discuss (i) how AICD,
      Abeta, and Tau reach the nucleus and how AICD and Abeta control protein
      expression at the transcriptional level, (ii) post-translational modifications of
      AICD, Abeta, and Tau, and (iii) what these three molecules have in common. 

PMID- 26296891
TI  - Rapid fine conformational epitope mapping using comprehensive mutagenesis and
      deep sequencing.
AB  - Knowledge of the fine location of neutralizing and non-neutralizing epitopes on
      human pathogens affords a better understanding of the structural basis of
      antibody efficacy, which will expedite rational design of vaccines,
      prophylactics, and therapeutics. However, full utilization of the wealth of
      information from single cell techniques and antibody repertoire sequencing awaits
      the development of a high throughput, inexpensive method to map the
      conformational epitopes for antibody-antigen interactions. Here we show such an
      approach that combines comprehensive mutagenesis, cell surface display, and DNA
      deep sequencing. We develop analytical equations to identify epitope positions
      and show the method effectiveness by mapping the fine epitope for different
      antibodies targeting TNF, pertussis toxin, and the cancer target TROP2. In all
      three cases, the experimentally determined conformational epitope was consistent
      with previous experimental datasets, confirming the reliability of the
      experimental pipeline. Once the comprehensive library is generated, fine
      conformational epitope maps can be prepared at a rate of four per day. 

PMID- 26296892
TI  - Differential Recognition Preferences of the Three Src Homology 3 (SH3) Domains
      from the Adaptor CD2-associated Protein (CD2AP) and Direct Association with Ras
      and Rab Interactor 3 (RIN3).
AB  - CD2AP is an adaptor protein involved in membrane trafficking, with essential
      roles in maintaining podocyte function within the kidney glomerulus. CD2AP
      contains three Src homology 3 (SH3) domains that mediate multiple protein-protein
      interactions. However, a detailed comparison of the molecular binding preferences
      of each SH3 remained unexplored, as well as the discovery of novel interactors.
      Thus, we studied the binding properties of each SH3 domain to the known
      interactor Casitas B-lineage lymphoma protein (c-CBL), conducted a peptide array
      screen based on the recognition motif PxPxPR and identified 40 known or novel
      candidate binding proteins, such as RIN3, a RAB5-activating guanine nucleotide
      exchange factor. CD2AP SH3 domains 1 and 2 generally bound with similar
      characteristics and specificities, whereas the SH3-3 domain bound more weakly to
      most peptide ligands tested yet recognized an unusually extended sequence in ALG
      2-interacting protein X (ALIX). RIN3 peptide scanning arrays revealed two CD2AP
      binding sites, recognized by all three SH3 domains, but SH3-3 appeared non
      functional in precipitation experiments. RIN3 recruited CD2AP to RAB5a-positive
      early endosomes via these interaction sites. Permutation arrays and isothermal
      titration calorimetry data showed that the preferred binding motif is Px(P/A)xPR.
      Two high-resolution crystal structures (1.65 and 1.11 A) of CD2AP SH3-1 and SH3-2
      solved in complex with RIN3 epitopes 1 and 2, respectively, indicated that
      another extended motif is relevant in epitope 2. In conclusion, we have
      discovered novel interaction candidates for CD2AP and characterized subtle yet
      significant differences in the recognition preferences of its three SH3 domains
      for c-CBL, ALIX, and RIN3. 

PMID- 26296894
TI  - Human Mincle Binds to Cholesterol Crystals and Triggers Innate Immune Responses.
AB  - C-type lectin receptors (CLRs) are an emerging family of pattern recognition
      receptors that recognizes pathogens or damaged tissue to trigger innate immune
      responses. However, endogenous ligands for CLRs are not fully understood. In this
      study, we sought to identify an endogenous ligand(s) for human macrophage
      inducible C-type lectin (hMincle). A particular fraction of lipid extracts from
      liver selectively activated reporter cells expressing hMincle. MS analysis
      determined the chemical structure of the active component as cholesterol.
      Purified cholesterol in plate-coated and crystalized forms activates reporter
      cells expressing hMincle but not murine Mincle (mMincle). Cholesterol crystals
      are known to activate immune cells and induce inflammatory responses through
      lysosomal damage. However, direct innate immune receptors for cholesterol
      crystals have not been identified. Murine macrophages transfected with hMincle
      responded to cholesterol crystals by producing pro-inflammatory cytokines. Human
      dendritic cells expressed a set of inflammatory genes in response to cholesterol
      crystals, and this was inhibited by anti-human Mincle. Importantly, other related
      CLRs did not bind cholesterol crystals, whereas other steroids were not
      recognized by hMincle. These results suggest that cholesterol crystals are an
      endogenous ligand for hMincle and that they activate innate immune responses. 

PMID- 26296893
TI  - The E3 ubiquitin ligases, HUWE1 and NEDD4-1, are involved in the post
      translational regulation of the ABCG1 and ABCG4 lipid transporters.
AB  - The ATP-binding cassette transporter ABCG1 has an essential role in cellular
      cholesterol homeostasis, and dysregulation has been associated with a number of
      high burden diseases. Previous studies reported that ABCG1 is ubiquitinated and
      degraded via the ubiquitin proteasome system. However, so far the molecular
      mechanism, including the identity of any of the rate-limiting ubiquitination
      enzymes, or E3 ligases, is unknown. Using liquid chromatography mass
      spectrometry, we identified two HECT domain E3 ligases associated with ABCG1,
      named HUWE1 (HECT, UBA, and WWE domain containing 1, E3 ubiquitin protein ligase)
      and NEDD4-1 (Neural precursor cell-expressed developmentally down regulated gene
      4), of which the latter is the founding member of the NEDD4 family of ubiquitin
      ligases. Silencing both HUWE1 and NEDD4-1 in cells overexpressing human ABCG1
      significantly increased levels of the ABCG1 monomeric and dimeric protein forms,
      however ABCA1 protein expression was unaffected. In addition, ligase silencing
      increased ABCG1-mediated cholesterol export to HDL in cells overexpressing the
      transporter as well as in THP-1 macrophages. Reciprocally, overexpression of both
      ligases resulted in a significant reduction in protein levels of both the ABCG1
      monomeric and dimeric forms. Like ABCG1, ABCG4 protein levels and cholesterol
      export activity were significantly increased after silencing both HUWE1 and NEDD4
      1 in cells overexpressing this closely related ABC half-transporter. In summary,
      we have identified for the first time two E3 ligases that are fundamental enzymes
      in the post-translational regulation of ABCG1 and ABCG4 protein levels and
      cellular cholesterol export activity. 

PMID- 26296896
TI  - Predictive value of thrombospondin-1 for outcomes in patients with acute ischemic
      stroke.
AB  - BACKGROUND: Thrombospondin-1 is a potent regulator of angiogenesis. The
      expression of cerebral thrombospondin-1 is promoted in a rat model of
      intracerebral hemorrhage. The current study was designed to investigate the
      change of plasma thrombospondin-1 concentrations and assess the prognostic value
      of plasma thrombospondin-1 concentrations for long-term mortality and functional
      outcome of ischemic stroke patients. METHODS: This study included 192 patients
      and 150 healthy controls. The plasma thrombospondin-1 concentrations were
      measured using enzyme-linked immunosorbent assay. An unfavorable outcome was
      defined as a modified Rankin Scale score >3. The relationships between plasma
      thrombospondin-1 concentrations and 6-month clinical outcomes were analyzed using
      multivariate analysis. RESULTS: Compared with healthy controls, plasma
      thrombospondin-1 concentrations were statistically significantly elevated in
      patients. Using multivariate analysis, thrombospondin-1 emerged as an independent
      predictor for 6-month mortality, 6-month unfavorable outcome and 6-month overall
      survival. Plasma thrombospondin-1 concentrations possessed high predictive values
      under receiver operating characteristic curve. Their predictive values were
      similar to those of National Institutes of Health Stroke Scale scores.
      CONCLUSIONS: Plasma thrombospondin-1 concentrations are elevated obviously and
      are highly associated with long-term outcome of ischemic stroke.

PMID- 26296895
TI  - Multiple Surface Regions on the Niemann-Pick C2 Protein Facilitate Intracellular
      Cholesterol Transport.
AB  - The cholesterol storage disorder Niemann-Pick type C (NPC) disease is caused by
      defects in either of two late endosomal/lysosomal proteins, NPC1 and NPC2. NPC2
      is a 16-kDa soluble protein that binds cholesterol in a 1:1 stoichiometry and can
      transfer cholesterol between membranes by a mechanism that involves protein
      membrane interactions. To examine the structural basis of NPC2 function in
      cholesterol trafficking, a series of point mutations were generated across the
      surface of the protein. Several NPC2 mutants exhibited deficient sterol transport
      properties in a set of fluorescence-based assays. Notably, these mutants were
      also unable to promote egress of accumulated intracellular cholesterol from npc2(
      /-) fibroblasts. The mutations mapped to several regions on the protein surface,
      suggesting that NPC2 can bind to more than one membrane simultaneously. Indeed,
      we have previously demonstrated that WT NPC2 promotes vesicle-vesicle
      interactions. These interactions were abrogated, however, by mutations causing
      defective sterol transfer properties. Molecular modeling shows that NPC2 is
      highly plastic, with several intense positively charged regions across the
      surface that could interact favorably with negatively charged membrane
      phospholipids. The point mutations generated in this study caused changes in NPC2
      surface charge distribution with minimal conformational changes. The plasticity,
      coupled with membrane flexibility, probably allows for multiple cholesterol
      transfer routes. Thus, we hypothesize that, in part, NPC2 rapidly traffics
      cholesterol between closely appositioned membranes within the multilamellar
      interior of late endosomal/lysosomal proteins, ultimately effecting cholesterol
      egress from this compartment.

PMID- 26296897
TI  - Utility of presepsin (sCD14-ST) as a diagnostic and prognostic marker of sepsis
      in the emergency department.
AB  - BACKGROUND: Presepsin (PSEP) is released during infectious diseases and can be
      detected in the blood. PSEP has shown promising results as sepsis marker. We
      examined the diagnostic and prognostic validity of PSEP in patients suspicious of
      sepsis on admission in the emergency department (ED). METHODS: One hundred twenty
      three patients with signs of SIRS and/or sepsis and 123 healthy individuals were
      enrolled. PSEP was determined on admission, after 8, 24 and 72 h. RESULTS: Mean
      PSEP concentrations of the control group and the patient group were 130 and 1945
      pg/ml. PSEP differed between SIRS, sepsis, severe sepsis and septic shock and
      showed strong association with 30-day mortality ranging from 10.3% in the 1st to
      32.1% in the 4th quartile. The ROC curve analyses revealed an AUC value of 0.743.
      Combined assessment of PSEP and MEDS score increased the AUC up to 0.878
      demonstrating the close relationship with outcome. Based on the PSEP values in
      the different severity degrees, decision thresholds for risk stratification were
      established. The course of PSEP during the first 72 h was associated with
      effectiveness of treatment and outcome. CONCLUSIONS: PSEP allowed outcome
      prediction already on admission to a similar degree as the clinical scores MEDS
      and APACHE II. Combination of PSEP with MEDS score improved the discriminatory
      power for outcome prediction.

PMID- 26296898
TI  - Interictal plasma pituitary adenylate cyclase-activating polypeptide levels are
      decreased in migraineurs but remain unchanged in patients with tension-type
      headache.
AB  - BACKGROUND: Pituitary adenylate cyclase-activating polypeptide (PACAP) is
      associated with migraine phase; however, whether PACAP levels could be used to
      distinguish between migraine and tension-type headache (TTH) remains unknown. We
      compared interictal plasma PACAP levels among healthy controls, migraineurs, and
      patients with TTH. METHODS: Interictal plasma levels of PACAP were measured in
      133 migraineurs, 106 patients with TTH, and 50 controls using enzyme-linked
      immunoassays. We further evaluated the relationships between interictal PACAP
      plasma concentrations and clinical parameters, such as headache severity, attack
      frequency, and duration. RESULTS: We found that migraineurs had significantly
      lower interictal plasma PACAP levels than patients with TTH and healthy controls.
      However, there were no significant differences between patients with TTH and
      healthy controls. Plasma PACAP levels were significantly lower in patients with
      episodic migraine (EM) than in patients with episodic tension-type headache
      (ETTH) and in patients with chronic migraine (CM) than in patients with chronic
      tension-type headache (CTTH). Interictal PACAP levels were negatively correlated
      with duration in the CM group. CONCLUSIONS: The results of this study
      demonstrated differences in interictal PACAP levels in migraine and TTH,
      suggesting that PACAP is involved in the pathogenesis of migraine rather than
      TTH.

PMID- 26296899
TI  - Urine proteome analysis to evaluate protein biomarkers in children with autism.
AB  - BACKGROUND: Autism is a complex developmental disability for which no specific
      diagnostic markers have been identified so far. The present study aimed to
      evaluate whether there is any abnormal protein(s) excreted in the urine of
      autistic children by proteome analysis which may act as diagnostic marker.
      METHODS: Urine proteome analysis was carried out in first void urine samples of
      autistic and normal children (n=30) in the age group of 4-12 years by 2D-PAGE
      followed by MALDI-TOF-MS analysis. RESULTS: Comparison of 2D-PAGE gels revealed
      that many urinary proteins are expressed differentially in autistic children.
      Total numbers of spots observed were 250 and 159 in autism and normal samples
      respectively, out of which 95 matches were observed. In addition, 3 spots of
      abnormally expressed peptides were selected, excised and analyzed. Peptide
      sequence with significant match score was for kininogen-1 (KNG-1)-50 (spot-1),
      IgG1 heavy chain variable region-35(spot-2) and mannan-binding lectin serine
      protease-2 isoform-2 precursor-45(spot-3). All the autistic children showed
      significant increase (p<0.001) in urinary kininogen level measured quantitatively
      by ELISA, when compared to normal children. CONCLUSION: Increased urinary
      kininogen-1 level in all the autistic children and the possibility of this
      protein as a diagnostic marker need further investigation.

PMID- 26296900
TI  - Performance of PCR-based and Bioluminescent assays for mycoplasma detection.
AB  - Contaminated eukaryotic cell cultures are frequently responsible for unreliable
      results. Regulatory entities request that cell cultures must be mycoplasma-free.
      Mycoplasma contamination remains a significant problem for cell cultures and may
      have an impact on biological analysis since they affect many cell parameters. The
      gold standard microbiological assay for mycoplasma detection involves laborious
      and time-consuming protocols. PCR-based and Bioluminescent assays have been
      considered for routine cell culture screening in research laboratories since they
      are fast, easy and sensitive. Thus, the aim of this work is to compare the
      performance of two popular commercial assays, PCR-based and Bioluminescent
      assays, by assessing the level of mycoplasma contamination in cell cultures from
      Rio de Janeiro Cell Bank (RJCB) and also from customers' laboratories. The
      results obtained by both performed assays were confirmed by scanning electron
      microscopy. In addition, we evaluated the limit of detection of the PCR kit under
      our laboratory conditions and the storage effects on mycoplasma detection in
      frozen cell culture supernatants. The performance of both assays for mycoplasma
      detection was not significantly different and they showed very good agreement.
      The Bioluminescent assay for mycoplasma detection was slightly more dependable
      than PCR-based due to the lack of inconclusive results produced by the first
      technique, especially considering the ability to detect mycoplasma contamination
      in frozen cell culture supernatants. However, cell lines should be precultured
      for four days or more without antibiotics to obtain safe results. On the other
      hand, a false negative result was obtained by using this biochemical approach.
      The implementation of fast and reliable mycoplasma testing methods is an
      important technical and regulatory issue and PCR-based and Bioluminescent assays
      may be good candidates. However, validation studies are needed. 

PMID- 26296901
TI  - Alteromonas confluentis sp. nov., isolated from the junction between the ocean
      and a freshwater spring.
AB  - A Gram-stain-negative, aerobic, non-spore-forming, non-flagellated and coccoid,
      ovoid or rod-shaped bacterial strain, DSSK2-12T, was isolated from the place
      where the ocean and a freshwater spring meet at Jeju island, South Korea. Strain
      DSSK2-12T grew optimally at 30  degrees C, at pH 7.0-8.0 and in the presence of
      2.0 % (w/v) NaCl. The neighbour-joining phylogenetic tree based on 16S rRNA gene
      sequences revealed that strain DSSK2-12T fell within the clade comprising the
      type strains of species of the genus Alteromonas. Strain DSSK2-12T exhibited 16S
      rRNA gene sequence similarity values of 97.2-98.1 % to the type strains of
      Alteromonas litorea, Alteromonas marina, Alteromonas hispanica and Alteromonas
      genovensis and of 95.39-96.98 % to those of other species of the genus
      Alteromonas. Strain DSSK2-12T contained Q-8 as the predominant ubiquinone and
      summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c), C16 : 0 and C18 :
      1omega7c as the major fatty acids. The major polar lipids of strain DSSK2-12T
      were phosphatidylethanolamine, phosphatidylglycerol and one unidentified
      aminolipid. The DNA G+C content of strain DSSK2-12T was 48.6 mol% and its mean
      DNA-DNA relatedness values with the type strains of A. litorea, A. marina, A.
      hispanica and A. genovensis were 9-21 %. The differential phenotypic properties,
      together with phylogenetic and genetic distinctiveness, revealed that strain
      DSSK2-12T is separated from other species of the genus Alteromonas. On the basis
      of the data presented, strain DSSK2-12T is considered to represent a novel
      species of the genus Alteromonas, for which the name Alteromonas confluentis sp.
      nov. is proposed. The type strain is DSSK2-12T ( = KCTC 42603T = CECT 8870T).

PMID- 26296902
TI  - Right ventricular diastolic function in patients with community-acquired
      pneumonia.

PMID- 26296903
TI  - Improving emergency physician performance using audit and feedback: a systematic
      review.
AB  - BACKGROUND: Audit and feedback can decrease variation and improve the quality of
      care in a variety of health care settings. There is a growing literature on audit
      and feedback in the emergency department (ED) setting. Because most studies have
      been small and not focused on a single clinical process, systematic assessment
      could determine the effectiveness of audit and feedback interventions in the ED
      and which specific characteristics improve the quality of emergency care.
      OBJECTIVE: The objective of the study is to assess the effect of audit and
      feedback on emergency physician performance and identify features critical to
      success. METHODS: We adhered to the PRISMA statement to conduct a systematic
      review of the literature from January 1994 to January 2014 related to audit and
      feedback of physicians in the ED. We searched Medline, EMBASE, PsycINFO, and
      PubMed databases. We included studies that were conducted in the ED and reported
      quantitative outcomes with interventions using both audit and feedback. For
      included studies, 2 reviewers independently assessed methodological quality using
      the validated Downs and Black checklist for nonrandomized studies. Treatment
      effect and heterogeneity were to be reported via meta-analysis and the I2
      inconsistency index. RESULTS: The search yielded 4332 articles, all of which
      underwent title review; 780 abstracts and 131 full-text articles were reviewed.
      Of these, 24 studies met inclusion criteria with an average Downs and Black score
      of 15.6 of 30 (range, 6-22). Improved performance was reported in 23 of the 24
      studies. Six studies reported sufficient outcome data to conduct summary
      analysis. Pooled data from studies that included 41,124 patients yielded an
      average treatment effect among physicians of 36% (SD, 16%) with high
      heterogeneity (I2=83%). CONCLUSION: The literature on audit and feedback in the
      ED reports positive results for interventions across numerous clinical conditions
      but without standardized reporting sufficient for meta-analysis. Characteristics
      of audit and feedback interventions that were used in a majority of studies were
      feedback that targeted errors of omission and that was explicit with measurable
      instruction and a plan for change delivered in the clinical setting greater than
      1 week after the audited performance using a combination of media and types at
      both the individual and group levels. Future work should use standardized
      reporting to identify the specific aspects of audit or feedback that drive
      effectiveness in the ED.

PMID- 26296904
TI  - Prolonged cooling duration mitigates myocardial and cerebral damage in cardiac
      arrest.
AB  - BACKGROUND: The purpose of this study was to investigate the effect of prolonged
      cooling on cardiac and cerebral injury in animals under cardiac arrest. METHODS:
      Adult male Wistar rats were equally randomized to normothermia, 5H1, 5H2, 7H1,
      7H2, and 7H4 groups. The first number in the group name indicated ventricular
      fibrillation duration (minutes), the middle H indicated hypothermia, and the last
      number signified hypothermia duration (hours). Ventricular fibrillation was
      induced and untreated for 5 minutes (normothermia, 5H1, and 5H2) or 7 minutes
      (7H1, 7H2, and 7H4) followed by 1 minute of cardiopulmonary resuscitation
      followed by electric shocks. Hypothermia was initiated simultaneously with
      cardiopulmonary resuscitation initiation and maintained for 1 hour (5H1 and 7H1),
      2 hours (5H2 and 7H2) or 4 hours (7H4). RESULTS: There were 12 rats in each
      group. Compared with the 7H1 group, the 7H4 group had significantly better
      systolic function (dp/dt40) and cardiac output within the early postcardiac
      arrest period. Histologic examination disclosed less myocardial and hippocampal
      damage in the 7H4 group than the 7H1 group and in the 5H2 group than the 5H1
      group. Plasma troponin I, fatty acid-binding protein, and S-100beta
      concentrations were significantly lower in the 7H4 and 5H2 groups. The 7H4 and
      5H2 groups survived statistically longer than the groups with shorter cooling
      duration. CONCLUSION: Slightly prolonging hypothermia may mitigate myocardial and
      cerebral damage and improve survival and neurologic outcomes in a rat model of
      ventricular fibrillation cardiac arrest.

PMID- 26296905
TI  - Paget-Schroetter syndrome: diagnostic limitations of imaging upper extremity deep
      vein thrombosis.
AB  - Paget-Schroetter syndrome is a rare but potentially debilitating condition
      affecting young, otherwise healthy individuals. This condition, also known as
      effort thrombosis, is an upper extremity deep vein thrombosis classically caused
      by anatomical abnormalities compressing the neurovascular structures of the
      thoracic outlet. The diagnosis is important to emergency medicine providers due
      to its secondary morbidity and mortality. Common complications affecting these
      active adults are pulmonary embolism and postthrombotic syndrome. Most patients
      report a precedent history of vigorous exercise or activity involving the upper
      extremities. We present a case of a 23-year-old man with redness and swelling of
      his dominant arm after weightlifting. Previous literature describes Paget
      Schroetter syndrome from repetitive activities. The report highlights the
      limitations of imaging studies in proximal upper extremity deep vein thromboses.
      The initial selected imaging study, Doppler ultrasound, was negative in our case
      and was followed by a nondiagnostic computed tomographic venogram. Although
      ultrasound is the preferred diagnostic imaging modality, it is limited when
      thrombosis is present in the noncompressible region of the clavicle. Magnetic
      resonance venogram or computed tomographic venogram is recommended if index of
      suspicion is high and the ultrasound shows normal results, but these studies are
      highly dependent on technique, flow, and timing. The eventual diagnosis of
      axillosubclavian thrombosis was obtained only after specialty consultation and
      formal venography. This case discusses the limitations of each imaging modality
      and the importance of a comprehensive clinical approach to this rare diagnosis.

PMID- 26296906
TI  - Chronic central leptin infusion modulates the glycemia response to insulin
      administration in male rats through regulation of hepatic glucose metabolism.
AB  - Leptin and insulin use overlapping signaling mechanisms to modify hepatic glucose
      metabolism, which is critical in maintaining normal glycemia. We examined the
      effect of an increase in central leptin and insulin on hepatic glucose metabolism
      and its influence on serum glucose levels. Chronic leptin infusion increased
      serum leptin and reduced hepatic SH-phosphotyrosine phosphatase 1, the
      association of suppressor of cytokine signaling 3 to the insulin receptor in
      liver and the rise in glycemia induced by central insulin. Leptin also decreased
      hepatic phosphoenolpyruvate carboxykinase levels and increased insulin's ability
      to phosphorylate insulin receptor substrate-1, Akt and glycogen synthase kinase
      on Ser9 and to stimulate glucose transporter 2 and glycogen levels. Peripheral
      leptin treatment reproduced some of these changes, but to a lesser extent. Our
      data indicate that leptin increases the hepatic response to a rise in insulin,
      suggesting that pharmacological manipulation of leptin targets may be of interest
      for controlling glycemia. 

PMID- 26296907
TI  - The Src non-receptor tyrosine kinase paradigm: New insights into mammalian
      Sertoli cell biology.
AB  - Src kinases are non-receptor tyrosine kinases that phosphorylate diverse
      substrates, which control processes such as cell proliferation, differentiation
      and survival; cell adhesion; and cell motility. c-Src, the prototypical member of
      this protein family, is widely expressed by several organs that include the
      testis. In the seminiferous epithelium of the adult rat testis, c-Src is highest
      at the tubule lumen during the release of mature spermatids. Other studies show
      that testosterone regulates spermatid adhesion to Sertoli cells via c-Src,
      indicating Src phosphorylates key substrates that prompt the disassembly of
      Sertoli cell-spermatid junctions. A more recent in vitro study reveals that c-Src
      participates in the internalization of proteins that constitute the blood-testis
      barrier, which is present between Sertoli cells, suggesting a similar mechanism
      of junction disassembly is at play during spermiation. In this review, we discuss
      recent findings on c-Src, with an emphasis on its role in spermatogenesis in the
      mammalian testis.

PMID- 26296908
TI  - Implementation of geriatric assessment-based recommendations in older patients
      with cancer: A multicentre prospective study.
AB  - PURPOSE: The main objective of this study was to describe geriatric
      recommendations based on a geriatric assessment (GA) and to evaluate the
      implementation of these recommendations. PATIENTS AND METHODS: A two-step
      approach of screening followed by a GA was implemented in nine hospitals in
      Belgium. Patients >= 70 years were included at diagnosis or at disease
      progression/relapse. Concrete geriatric recommendations were systematically
      documented and reported to the treating physicians and consisted of referrals to
      professional health care workers. Patient charts were reviewed after one month to
      verify which geriatric recommendations have been performed. RESULTS: From August
      2011 to July 2012, 1550 patients were included for analysis. The median age was
      77 (range: 70-97) and 57.0% were female. A solid tumour was diagnosed in 91.4%
      and a haematological malignancy in 8.6%. Geriatric screening with the G8
      identified 63.6% of the patients for GA (n=986). A median of two geriatric
      recommendations (range: 1-6) were given for 76.2% (95%CI: 73.4-78.8) of the
      evaluable patients (n=710). A median of one geriatric recommendation (range: 1-5)
      was performed in 52.1% (95%CI: 48.4-55.8) of the evaluable patients (n=689). In
      general, 460 or 35.3% (95%CI: 32.8-38.0) of all the geriatric recommendations
      were performed. Geriatric recommendations most frequently consisted of referrals
      to the dietician (60.4%), social worker (40.3%), and psychologist (28.9%).
      CONCLUSION: This implementation study provides insight into GA-based
      recommendations/interventions in daily oncology practice. Geriatric
      recommendations were given in about three-fourths of patients. About one-third of
      all geriatric recommendations were performed in approximately half of these
      patients.

PMID- 26296910
TI  - Surgical management of metastatic colon cancer: A population-based analysis.
AB  - BACKGROUND: Metastasectomy has a curative potential in colon cancer, but its
      benefits have not been ascertained in population data. Our objective was to
      evaluate utilization of metastasectomy in colon cancer and its survival outcomes
      in groups defined by different age at diagnosis, tumor grade or varying extent of
      nodal spread. METHODS: We extracted data from the Surveillance, Epidemiology and
      End Results database on adult patients with stage IV colon cancer diagnosed
      between 2003 and 2011. We analyzed the association of overall survival (OS) with
      metastasectomy using multivariable Cox models. RESULTS: Among 41,137 patients
      with stage IV cancer, 26,607 (65%) underwent primary surgery and 5028 (12.2%)
      underwent metastasectomy. Older patients were less likely to have >=12 lymph
      nodes examined in the surgical specimen, but also less likely to have nodal
      metastases when adequately staged (from 86% for age <50 years to 79% for age >=85
      years). Metastasectomy was less common in older patients (from 18% for age <50
      years to 7% for age >=85 years). OS after resection was inversely associated with
      age and nodal involvement. The association of metastasectomy with survival was
      favorable in all age groups (hazard ratio, HR, 0.68-0.72, P<0.0001), but it was
      not significant for those >=85y ears old (HR, 0.92, P=0.23). It was also
      favorable regardless of the extent of nodal spread or tumor grade. CONCLUSIONS:
      Resection of metastatic site is favorably associated with survival in patients up
      to 85 years of age. Older patients undergoing metastasectomy are more likely to
      be node-negative when adequately staged.

PMID- 26296909
TI  - Patterns of care and outcomes of older versus younger patients with metastatic
      pancreatic cancer: A Fox Chase Cancer Center experience.
AB  - BACKGROUND: Older patients with metastatic pancreatic cancer (mPC) are poorly
      represented in clinical trials. We compared patterns of care and outcomes of
      patients with mPC < and >65 yrs (Group 1 and Group 2, respectively) treated at
      Fox Chase Cancer Center (FCCC) to identify predictors of survival and better
      understand the treatment approaches. METHODS: Charts of 579 patients with mPC
      treated at FCCC from 2000 to 2010 were reviewed. Group 1 and Group 2 were
      compared with respect to baseline, treatment characteristics, and overall
      survival (OS) after diagnosis of metastatic disease. RESULTS: 299 patients in
      Group 1 (median age 57) and 280 patients in Group 2 (median age 73) were
      evaluated. Patients in Group 2 were less likely to receive any chemotherapy for
      mPC compared to Group 1 (65% vs 75%, p=0.001) and if treated were less likely to
      receive more than one agent (37% vs 53%, p<0.001). Survival was comparable
      between the two groups (p=0.16) and Charlson Co-morbidity Index did not emerge as
      a prognostic factor. Longer OS was associated with higher number of agents used
      in both groups (p<0.001). Liver metastases conferred worse survival (p=0.02)
      while lung metastases conferred better survival in both groups (p=0.002).
      CONCLUSIONS: Older mPC patients are less likely to receive chemotherapy and
      receive fewer agents yet have similar OS compared to younger patients. OS
      improves with increasing number of agents, supporting the use of combination
      chemotherapy in healthy older patients. Our findings encourage enrollment of
      older patients with mPC with good performance status onto clinical trials with
      stratification by site of metastases.

PMID- 26296911
TI  - 3-Benzamides and 3,4,5-trimethoxyphenyl amines as calcium channel blockers.
AB  - T- and N-type calcium channels have known for relating to therapy of neuropathic
      pain which is chronic, debilitating pain state. Neuropathic pain is caused by
      damage of the somatosensory system. It may be associated with abnormal sensations
      and pain produced by normally non-painful stimuli (allodynia). Neuropathic pain
      is very difficult to treat, and only some 40-60% of patients achieve partial
      relief. For a neuropathic pain therapy, anticonvulsant like Lamotrigine,
      Carbamazepine and a topical anesthetic such as Lidocaine are used. We synthesized
      15 novel amine derivatives and evaluated their activities against T-type and N
      type calcium channels by whole-cell patch clamp recording on HEK293 cells. Among
      the tested compounds, compound 10 showed good inhibitory activity for both T-type
      and N-type calcium channels with the IC50 value of 1.9 MUM and 4.3 MUM,
      respectively. Compound 10 also showed good analgesic activity on rat spinal cord
      injury model.

PMID- 26296912
TI  - Synthesis, resolution and biological evaluation of cyclopropyl analogs of
      abscisic acid.
AB  - cis-2,3-Cyclopropanated abscisic acid (cis-CpABA) has high photostability and
      good ABA-like activity. To further investigate its activity and action mechanism,
      2S,3S-2,3-cyclopropanated ABA (3a) and 2R,3R-2,3-cyclopropanated ABA (3b) were
      synthesized. Bioassay showed that 3a displayed higher inhibitory activity in
      germination than that of 3b and ABA at the concentration of 3.0 MUM, but 3a and
      3b had much weaker inhibitory activity in inhibition seedling growth compared to
      ABA. The study of photostability revealed that 3a and 3b showed high stability
      under UV light exposure, which were 4 times and 3 times greater than (+/-)-ABA,
      respectively. Action mechanism study showed that 3a presented higher inhibition
      on phosphatase activity of HAB1 than 3b, although they all inferior to ABA.
      Molecular docking studies of 3a, 3b and ABA receptor PYL10 were agreement with
      the bioassay data and confirmed the importance of the configuration of the 2,3
      cyclopropyl ABA analogs for their bioactivity in somewhat. This study provides a
      new approach for the design of ABA analogs, and the results validated structure
      based design for this target class.

PMID- 26296913
TI  - Substrate-guided optimization of the syringolins yields potent proteasome
      inhibitors with activity against leukemia cell lines.
AB  - Natural products that inhibit the proteasome have been fruitful starting points
      for the development of drug candidates. Those of the syringolin family have been
      underexploited in this context. Using the published model for substrate mimicry
      by the syringolins and knowledge about the substrate preferences of the
      proteolytic subunits of the human proteasome, we have designed, synthesized, and
      evaluated syringolin analogs. As some of our analogs inhibit the activity of the
      proteasome with second-order rate constants 5-fold greater than that of the
      methyl ester of syringolin B, we conclude that the substrate mimicry model for
      the syringolins is valid. The improvements in in vitro potency and the activities
      of particular analogs against leukemia cell lines are strong bases for further
      development of the syringolins as anti-cancer drugs.

PMID- 26296914
TI  - Porcine endogenous retrovirus-A/C: biochemical properties of its integrase and
      susceptibility to raltegravir.
AB  - Porcine endogenous retroviruses (PERVs) are present in the genomes of pig cells.
      The PERV-A/C recombinant virus can infect human cells and is a major risk of
      zoonotic disease in the case of xenotransplantation of pig organs to humans.
      Raltegravir (RAL) is a viral integrase (IN) inhibitor used in highly active
      antiretroviral treatment. In the present study, we explored the potential use of
      RAL against PERV-A/C. We report (i) a three-dimensional model of the PERV-A/C
      intasome complexed with RAL, (ii) the sensitivity of PERV-A/C IN to RAL in vitro
      and (iii) the sensitivity of a PERV-A/C-IRES-GFP recombinant virus to RAL in
      cellulo. We demonstrated that RAL is a potent inhibitor against PERV-A/C IN and
      PERV-A/C replication with IC50s in the nanomolar range. To date, the use of
      retroviral inhibitors remains the only way to control the risk of zoonotic PERV
      infection during pig-to-human xenotransplantation. 

PMID- 26296915
TI  - Medullary nephritis in the diagnosis of acute cellular rejection.
AB  - BACKGROUND: The purpose of this study was to understand the role of
      lymphomononuclear inflammation (nephritis) in the renal allograft medulla of
      transplant recipients with acute dysfunction, by comparing the immunophenotype of
      inflammatory cells present in the medulla and cortex of kidney graft biopsies.
      METHOD: This is a retrospective study of 113 renal allograft needle biopsies,
      presenting with medullary nephritis, divided into two groups according to the
      main location of nephritis: in cortical and medullary regions (corticomedullary
      nephritis) or exclusively in the medullary region (medullary nephritis). We
      performed immunohistochemistry (IHC) of the cells composing the inflammatory
      foci, using anti-CD4, CD8, CD20, CD68, and CD138 antibodies, respectively for T
      helper cells, cytotoxic T cells, B lymphocytes, macrophages and plasmocytes. The
      clinical follow-up of the patients was correlated with the morphological
      findings. RESULTS: The nephritis was corticomedullary in 66 of the 113 cases
      (58.4%) and exclusively medullary in the remaining 47 cases (41.6%). The
      immunophenotype of the inflammatory cells was similar in the cortical and
      medullary compartments and were mainly: cytotoxic T lymphocytes (CD8) and
      macrophages CD68. The immunosuppressive therapeutic response to acute cellular
      rejection (ACR), based on decreasing of serum creatinine values, was 81.8% in the
      patients of the corticomedullary nephritis group and 63.6% in those of the
      medullary nephritis group. CONCLUSION: Medullary nephritis in renal allograft
      biopsies may indicate ACR, as could be noted by the immunophenotype, which
      presented the same cellular mediators of rejection seen in the allograft cortex,
      and by the positive immunosuppressive therapeutic response observed in most
      patients.

PMID- 26296916
TI  - Identification of similarities and differences between myeloid and lymphoid acute
      leukemias using a gene-gene interaction network.
AB  - Acute myeloid leukemia (AML) is a cancer that affects the myeloid line of blood
      cells. Acute lymphoid leukemia (ALL) is a type of leukemia that targets the
      lymphoid line of blood cells. As the comparison of these two types facilitates in
      the understanding of their molecular pathology, exploring the similarities and
      differences in the mechanisms of them is worthwhile. We identified 28 novel AML-
      and ALL-related genes shared in both of them using a short path algorithm. By
      integrating gene ontology (GO) and KEGG pathway annotations, we revealed the
      underlying molecular features of AML and ALL. We finally obtained 160 optimal GO
      terms that could satisfactorily distinguish two types. Further analysis revealed
      that the results agree well with previous knowledge. Determining the common and
      different features between AML and ALL facilitates the classification of leukemia
      and is thus clinically relevant for exploring the molecular markers. 

PMID- 26296917
TI  - High expression of APRIL correlates with poor prognosis in clear cell renal cell
      carcinoma.
AB  - INTRODUCTION: The members of the Tumor Necrosis Factor Superfamily (TNFSF),
      including A PRoliferation Inducing Ligand (APRIL), have been studied in RCC and
      other tumors. In this study, we investigated the expression of APRIL in resected
      clear cell renal cell carcinoma (CCRCC) samples by immunohistochemistry (IHC) and
      analyzed its association with the clinicopathologic characteristics and prognosis
      of the patients. METHODS: We examined 206 CCRCC samples from patients who
      underwent radical or partial nephrectomy at Seoul National University Hospital
      between 1999 and 2002. Tissue microarray (TMA) blocks were made, and
      immunohistochemical staining for APRIL expression was performed. RESULTS: We
      classified the IHC results as high expression or low expression. Of the 206
      cases, 89 cases (43.2%) were classified as showing high expression, and 117 cases
      (56.8%) showed low expression. The high expression of APRIL was significantly
      correlated with higher Fuhrman nuclear grade and higher pathologic stage (p=0.000
      and 0.004), and we observed that the high expression of APRIL was significantly
      correlated with the overall survival of the patients (p=0.045) and cancer
      specific survival (p=0.020), but was not correlated with disease-free survival
      (p=0.106). In multivariate analysis adjusted for Fuhrman nuclear grade and
      pathologic stage, the high expression of APRIL was not an independent prognostic
      factor for CCRCC, as determined by overall survival (p=0.830) and cancer-specific
      survival (p=0.792). CONCLUSIONS: We found that the high expression of APRIL in
      CCRCCs was correlated with high Fuhrman nuclear grade, high pathologic stage, and
      poor overall and cancer-specific survival of the patients. However, it did not
      correlate with disease-free survival and was not an independent prognostic
      factor.

PMID- 26296918
TI  - p53 immunoexpression in stepwise progression of cutaneous squamous cell carcinoma
      and correlation with angiogenesis and cellular proliferation.
AB  - Multistep carcinogenesis involves loss of function of tumor suppressor proteins
      such as p53 and induction of angiogenesis. Such mechanisms contribute to
      cutaneous squamous cell carcinoma progression and may be interconnected. We aimed
      to explore p53 immunoexpression in spectral stages of cutaneous squamous cell
      carcinoma and correlate expression to both neovascularization and cellular
      proliferation. We estimated the percentages of immunostained cells for p53 and
      Ki67 (proliferation marker) in three groups: 23 solar keratoses, 28 superficially
      invasive squamous cell carcinomas and 28 invasive squamous cell carcinomas. The
      Chalkley method was used to quantify the microvascular area by neoangiogenesis
      (CD105) immunomarker in each group. There was no significant difference for rate
      of p53- and Ki67-positive cells between groups. Significant positive correlation
      was found between the CD105 microvascular area and the rate of p53 positive cells
      in superficially invasive squamous cell carcinoma as well as between the rate of
      p53- and Ki67-positive cells in invasive squamous cell carcinoma. p53 and Ki67
      immunoexpression did not increase with cutaneous squamous cell carcinoma
      progression. Neovascularization in the initial stage of invasion and
      proliferative activity in the frankly invasive stage were both associated with
      p53 immunoexpression. Loss of p53 tumor suppressor function through progressive
      steps may be directly involved in skin carcinogenesis. 

PMID- 26296919
TI  - Expression of VEGF-C/-D and lymphangiogenesis in salivary adenoid cystic
      carcinoma.
AB  - AIMS: Some human neoplasms stimulate lymphangiogenesis through the over
      production of vascular endothelial growth factors C/D (VEGF-C/D). Previously
      little attention has been paid to the mechanisms of lymphogenous spread of
      salivary adenoid cystic carcinoma (SACC). The current study investigates the
      presence of lymphatic network and the role of VEGF-C and VEGF-D in its formation.
      METHODS: The retrospective study was performed in 20 (12 females and 8 males)
      patients diagnosed with SACC. For the evaluation of VEGF-C/D immunoreactivity,
      semiquantitative histoscore was calculated as a sum of positive tumor cell score
      (range 0-3) and staining intensity (range 0-3). Lymphatic vessel density (LVD)
      was determined as the number of D2-40 positive lymphatic capillaries present at
      "hot spots". Moreover, the values of histoscores were calculated in surrounding
      normal parotid parenchyma and compared to those counted in tumors. LVD in the
      tumor center (iLVD), in its periphery (pLVD), and in healthy gland were
      identified. RESULTS: VEGF-C/D expression, iLVD and pLVD were higher in SACC than
      in normal gland. The VEGF-C/D score correlated neither with pLVD nor with iLVD.
      High iLVD values were associated with poor survival. CONCLUSIONS: The authors
      present the first study demonstrating the existence of lymphatic vessels in SACC.

PMID- 26296920
TI  - Immunoexpression of EGFR and EMMPRIN in a series of cases of head and neck
      squamous cell carcinoma.
AB  - BACKGROUND: The epidermal growth factor receptor (EGFR) and the extracellular
      matrix metalloproteinase inducer (EMMPRIN) have been identified as oncologically
      important targets. This study aimed to evaluate the immunoexpression of EGFR and
      EMMPRIN in a series of cases of head and neck squamous cell carcinoma (HNSCC).
      METHODS: Forty-five cases of HNSCC were selected for this study and evaluated
      with anti-EGFR and anti-EMMPRIN antibodies. The percentage of positive cells was
      determined assessing to the following categories: score 1 (staining in 0-50% of
      cells), score 2 (staining in 51-75% of cells), and score 3 (staining in >75% of
      cells). Immunostaining intensity was graded according to the following
      parameters: score 1 (absent/weak expression) and score 2 (strong expression).
      RESULTS: For EGFR, a predominance of high median scores was observed in cases of
      both histological grades of malignancy and in different clinical stages (p>0.05).
      For EMMPRIN, a statistically significant difference was observed between the
      histological grades of malignancy (p=0.030). Regarding the immunostaining
      intensity of EMMPRIN, it was observed a predominance of score 1 in cases with
      stages I/II, whereas most cases with stages III/IV presented score 2 (p=0.032).
      Considering the anatomical location, most cases of buccal floor presented higher
      median score of EMMPRIN in comparison with the other sites (p=0.015).
      CONCLUSIONS: These findings suggest that both proteins are potential targets for
      cancer therapy and EMMPRIN can be used as a prognostic marker of a more
      aggressive biological behavior in patients with HNSCC.

PMID- 26296921
TI  - Menisectomized miniature Vietnamese pigs develop articular cartilage pathology
      resembling osteoarthritis.
AB  - Animal models have been used to understand the basic biology of osteoarthritis
      (OA) and have helped to identify new candidate biomarkers for the early diagnosis
      and treatment of this condition. Small animals cannot sufficiently mimic human
      diseases; therefore, large animal models are needed. Pigs have been used as
      models for human diseases because they are similar to humans in terms of their
      anatomy, physiology and genome. Hence, we analyzed articular cartilage and
      synovial membrane pathology in miniature Vietnamese pigs after a unilateral
      partial menisectomy and 20-day exercise regimen to determine if the pigs
      developed pathological characteristics similar to human OA. Histological and
      protein expression analysis of articular cartilage from menisectomized pigs
      revealed the following pathologic changes resembling OA: fibrillation, fissures,
      chondrocyte cluster formation, decrease in proteoglycan content and upregulation
      of the OA-associated proteins MMP-3, MMP-13, procaspase-3 and IL-1beta. Moreover,
      histological analysis of synovial membrane revealed mild synovitis, characterized
      by hyperplasia, cell infiltration and neoangiogenesis. Pathological changes were
      not observed in the contralateral joints or the joints of sham-operated pigs.
      Further studies are required to validate such an OA model; however, our results
      can encourage the use of pigs to study early stages of OA physiopathology. Based
      on their similarities to humans, pigs may be useful for preclinical studies to
      identify new candidate biomarkers and novel treatments for OA.

PMID- 26296922
TI  - Are cannabis laws used for political repression in the Arab Spring countries?

PMID- 26296923
TI  - Corticibacter populi gen. nov., sp. nov., a new member of the family
      Comamonadaceae, from the bark of Populus euramericana.
AB  - Three novel endophytic strains, designated 17B10-2-12T, 26C10-4-4 and D13-10-4-9,
      were isolated from the bark of Populus euramericana in Heze, Shandong Province,
      China. They were Gram-reaction-negative, aerobic, non-motile, short-rod-shaped,
      oxidase-positive and catalase-negative. A phylogenetic analysis of the 16S rRNA
      gene showed that the three novel strains clustered with members of the family
      Comamonadaceae and formed a distinct branch. The isolates shared 100 %
      similarities among themselves and had the highest sequence similarity with
      Xenophilus azovorans DSM 13620T (95.2 %) and Xenophilus arseniciresistens YW8T
      (95.0 %), and less than 95.0 % sequence similarities with members of other
      species. Their major fatty acids were C16 : 0, C17 : 0 cyclo, C18 : 1omega7c and
      C16 : 1omega7c/C16 : 1omega6c. The major polar lipids were
      diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and three
      unknown aminophospholipids. The predominant quinone was ubiquinone-8 (Q-8). The
      DNA G+C content was 69.5-70.0 mol%. Based on data from a polyphasic taxonomy
      study, the three strains represent a novel species of a novel genus of the family
      Comamonadaceae, for which the name Corticibacter populi gen. nov., sp. nov. is
      proposed. The type strain is 17B10-2-12T ( = CFCC 12099T = KCTC 42091T).

PMID- 26296924
TI  - Applying Lean Design Principles to a Gastrointestinal Endoscopy Program for
      Uninsured Patients Improves Health Care Utilization.

PMID- 26296925
TI  - Haliea atlantica sp. nov., isolated from seawater, transfer of Haliea
      mediterranea to Parahaliea gen. nov. as Parahaliea mediterranea comb. nov. and
      emended description of the genus Haliea.
AB  - A novel Gram-stain-negative, oxidase- and catalase-positive, aerobic bacterium,
      designated strain SM1351T, was isolated from surface seawater of the Atlantic
      Ocean. This strain grew at 4-45  degrees C and with 5-90 g NaCl l- 1. It did not
      reduce nitrate to nitrite and could not hydrolyse starch or DNA. Phylogenetic
      analysis based on 16S rRNA gene sequences revealed that the strain was affiliated
      with the genus Haliea in the family Alteromonadaceae, with sequence similarities
      with the type strains of Haliea salexigens and Haliea mediterranea, the two
      recognized species of the genus Haliea, of 96.2 and 94.6 %, respectively. The
      major fatty acids of strain SM1351T were C16 : 1omega7c and/or iso-C15 : 0 2-OH,
      C17 : 1omega8c, C18 : 1omega7c and C16 : 0 and the major polar lipids were
      phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. The
      major respiratory quinone was ubiquinone Q-8. The genomic DNA G+C content of
      strain SM1351T was 62 mol%. On the basis of the polyphasic characterization of
      strain SM1351T in this study, it is considered to represent a novel species in
      the genus Haliea, for which the name Haliea atlantica sp. nov. is proposed. The
      type strain is SM1351T ( = CCTCC AB 2014266T = JCM 30304T). Moreover, the
      transfer of Haliea mediterraneaLucena et al. 2010 to Parahaliea gen. nov. as
      Parahaliea mediterranea comb. nov. (type strain 7SM29T = CECT 7447T = DSM 21924T)
      and an emended description of the genus Haliea are also proposed. 

PMID- 26296926
TI  - High-Throughput Screening Strategy Identifies Allosteric, Covalent Human D-Amino
      Acid Oxidase Inhibitor.
AB  - Genome-wide association studies have linked polymorphisms in the gene G72 to
      schizophrenia risk in several human populations. Although controversial,
      biochemical experiments have suggested that the mechanistic link of G72 to
      schizophrenia is due to the G72 protein product, pLG72, exerting a regulatory
      effect on human D-amino acid oxidase (hDAAO) activity. In an effort to identify
      hDAAO inhibitors of novel mechanism of action, we designed a pLG72-directed hDAAO
      activity assay suitable for high-throughput screening (HTS). During assay
      development, we confirmed that pLG72 was an inhibitor of hDAAO. Thus, our assay
      employed an IC20 pLG72 concentration that was high enough to allow dynamic pLG72
      hDAAO complexes to form but with sufficient remaining hDAAO activity to measure
      during an HTS. After conducting an approximately 150,000-compound HTS, we further
      characterized a class of compound hits that were less potent hDAAO inhibitors
      when pLG72 was present. Focusing primarily on compound 2: [2-(2,5-dimethylphenyl)
      6-fluorobenzo[d]isothiazol-3(2H)-on], we demonstrated that these compounds
      inhibited hDAAO via an allosteric, covalent mechanism. Although there is
      significant interest in the therapeutic potential of compound 2: and its
      analogues, their sensitivity to reducing agents and their capacity to bind
      cysteines covalently would need to be addressed during therapeutic drug
      development. 

PMID- 26296927
TI  - Characterization of a new Helicoverpa armigera nucleopolyhedrovirus variant
      causing epizootic on a previously unreported host, Helicoverpa gelotopoeon
      (Lepidoptera: Noctuidae).
AB  - This paper reports the first biological and molecular characterization of a
      nucleopolyhedrovirus isolated from the soybean and cotton pest Helicoverpa
      gelotopoeon. Studies were performed following a virus outbreak in a rearing
      facility and in wild H. gelotopoeon populations in Cordoba, Argentina. Host
      identity was corroborated by partial sequencing of the COI gene. Scanning
      electron microscope observations of purified OBs revealed their polyhedral
      morphology and an average diameter of 0.89+/-0.14MUm. Ultrathin sections of
      infected larvae examined by transmission electron microscopy showed the
      intranuclear occurrence of polyhedra and virus particles in fat body cells.
      Nucleocapsids were singly enveloped. Phylogenetic analysis of lef-8, lef-9, polh,
      orf5/5b and hr3-orf62 viral sequences identified this new NPV isolate (hereafter
      HegeSNPV) as a variant of Helicoverpa armigera nucleopolyhedrovirus (HearNPV).
      Furthermore, HegeSNPV was closely related to the so-called "HzSNPV Group" within
      HearNPV, although having particular characteristics.

PMID- 26296928
TI  - Digital gene expression analysis of Helicoverpa armigera in the early stage of
      infection with Helicoverpa armigera nucleopolyhedrovirus.
AB  - Helicoverpa armigera single nucleocapsid nucleopolyhedrovirus (HearNPV) is an
      obligatory and lethal parasite of the cotton bollworm and has been extensively
      used in China for the control of this notorious pest. Digital gene expression
      (DGE) analysis was adopted for an overall comparison of transcriptome profiling
      between HearNPV-infected and control healthy Helicoverpa armigera larvae during
      an early stage post-inoculation. A total of 908 differentially expressed genes
      (DEGs) were identified, of which 136 were up-regulated and 597 were down
      regulated. GO category and KEGG pathway analysis demonstrated that the identified
      DEGs involved in ribosome biogenesis, aminoacyl-tRNA biosynthesis, protein
      processing in endoplasmic reticulum, biosynthesis of valine, leucine, isoleucine
      and the spliceosome were significantly down-regulated, whereas genes involved in
      pancreatic secretion, protein digestion and absorption and salivary secretion
      showed obviously up-regulated transcription. The DEGs were verified by
      quantitative real-time PCR, and genes that participated in defensive response,
      nutritional digestion and developmental regulation exhibited specific expression
      patterns in a continuous time-course assessment. These results provide basic data
      for future research on the molecular mechanism of HearNPV infection and the
      interactions between lepidopteran hosts and their specific NPV parasites. 

PMID- 26296929
TI  - Randomized Clinical Trial of a Sustained-Exposure Ciprofloxacin for Intratympanic
      Injection During Tympanostomy Tube Surgery.
AB  - OBJECTIVE: This exploratory clinical trial evaluated the safety and clinical
      activity of a novel, sustained-exposure formulation of ciprofloxacin
      microparticulates in poloxamer (OTO-201) administered during tympanostomy tube
      placement in children. METHODS: Double-blind, randomized, prospective, placebo-
      and sham-controlled, multicenter Phase 1b trial in children (6 months to 12
      years) with bilateral middle ear effusion requiring tympanostomy tube placement.
      Patients were randomized to intraoperative OTO-201 (4 mg or 12 mg), placebo, or
      sham (2:1:1 ratio). RESULTS: Eighty-three patients (52 male/31 female; mean age,
      2.80 years) were followed for safety (otoscopic exams, cultures, audiometry, and
      tympanometry) and clinical activity, defined as treatment failure (physician
      documented otorrhea and/or otic or systemic antibiotic use >=3 days post
      surgery). At baseline, 14.3% to 36.8% of children showed positive cultures of
      middle ear effusion samples in at least 1 ear. Through day 15, treatment failures
      accounted for 14.3%, 15.8%, 45.5%, and 42.9% of patients (OTO-201 4 mg, OTO-201
      12 mg, placebo, and sham, respectively); treatment failure reductions for OTO-201
      doses were significant compared to pooled control (P values = .023 and .043,
      respectively). Observed OTO-201 safety profile was indistinguishable from placebo
      or sham. CONCLUSIONS: Results of this first clinical trial suggest that OTO-201
      was well tolerated and shows preliminary clinical activity in treating
      tympanostomy tube otorrhea.

PMID- 26296930
TI  - Tracheal and Crico-Tracheal Resection and Anastomosis for Malignancies Involving
      the Thyroid Gland and the Airway.
AB  - OBJECTIVES: To evaluate outcomes in different malignancies involving the thyroid
      and infiltrating the airway submitted to tracheal (TRA) or crico-tracheal
      resection and anastomosis (CTRA). METHODS: Retrospective charts review of 27
      patients affected by thyroid malignancies involving the airway treated by
      TRA/CTRA in a single academic institution. Kaplan-Meier curves were used to
      evaluate the overall (OS) and disease-specific (DSS) survivals and local (LC) and
      loco-regional control (LRC). Impact on survival of age, comorbidities, previous
      radiotherapy, types of TRA/CTRA, Shin's stage (II, III, IV), grading (well vs
      poorly differentiated), and length of airway resected was calculated by the log
      rank test. RESULTS: Overall survival and DSS at 3 and 5 years were 82.3% and
      71.6%, respectively. Local control and LRC in the entire group were 82.3% at 3
      and 5 years. Crico-tracheal resection and anastomosis involving the cricoid arch
      and plate (type C) and tumor differentiation significantly affected OS and DSS
      (both P < .001). Type C CTRA and tumor differentiation significantly impacted on
      LC (P = .002 and P = .009, respectively). CONCLUSIONS: Grading and extension of
      CTRA to the cricoid plate are the most important factors for oncologic outcomes
      in thyroid malignancies infiltrating the airway. Except for poorly differentiated
      tumors, TRA/CTRA allows adequate LC even in advanced stage lesions involving the
      crico-tracheal junction.

PMID- 26296931
TI  - Characterization of the medically important yeast Trichosporon mucoides and its
      close sister Trichosporon dermatis by traditional and advanced technologies.
AB  - Trichosporon dermatis is a causative agent of several mycoses in
      immunocompromised patients but is often misidentified as Trichosporon mucoides
      due to their phenotypic resemblance. In order to evaluate the current
      identification keys for these species and to develop a rapid and reliable
      identification method, 11 strains of these yeasts were fully characterized in
      this study by traditional and advanced technologies. DNA sequences of the
      internal transcribed spacer (ITS), IGS1, and D1/D2 regions identified six of the
      yeasts as T. dermatis that were previously known as T. mucoides, including ATCC
      204094 that has been used as the quality-control strain of T. mucoides for the
      VITEK 2 system and other commercial yeast identification kits. These two species
      could not be differentiated reliably by any previously known phenotypic keys for
      the species, such as growth patterns on ethylamine, phloroglucinol and tyramine,
      or by the VITEK 2 system. On the other hand, matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) proved to
      be a rapid and reliable identification tool for the two closely related yeasts.
      With newly added superspectra from fully authenticated reference strains, the
      VITEK MS system using MALDI-TOF MS successfully separated strains of T. dermatis
      and T. mucoides at a similarity level of approximately 67 % for the mass spectra
      data, and could identify these strains at the species level with 100 % accuracy
      in repeated tests. Furthermore, the in vitro susceptibility results indicated
      that itraconazole, posaconazole and voriconazole were more effective against both
      T. mucoides and T. dermatis than the other antifungal agents tested in this
      study. 

PMID- 26296932
TI  - Progress towards inducing tolerance of pig-to-primate xenografts.
AB  - Xenotransplantation remains the best near-term solution to the shortage of
      transplantable organs that currently limits the field of transplantation.
      However, because the immune response to xenografts is considerably stronger than
      it is to allografts, the amount of non-specific immunosuppression required to
      avoid xenograft rejection may limit clinical applicability. For this reason, we
      consider it likely that the success of clinical xenotransplantation will depend
      on finding ways of safely inducing tolerance across xenogeneic barriers rather
      than relying entirely on non-specific immunosuppressive agents. In this
      laboratory, two approaches are being studied for the induction of pig-to-primate
      tolerance: a) the simultaneous transplantation of vascularized thymus and solid
      organs; and b) mixed hematopoietic chimerism. A summary of the development of
      these two approaches and their current status is the subject of this review. 

PMID- 26296933
TI  - Genetics and pharmacology of longevity: the road to therapeutics for healthy
      aging.
AB  - Aging can be defined as the progressive decline in tissue and organismal function
      and the ability to respond to stress that occurs in association with homeostatic
      failure and the accumulation of molecular damage. Aging is the biggest risk
      factor for human disease and results in a wide range of aging pathologies.
      Although we do not completely understand the underlying molecular basis that
      drives the aging process, we have gained exceptional insights into the plasticity
      of life span and healthspan from the use of model organisms such as the worm
      Caenorhabditis elegans and the fruit fly Drosophila melanogaster. Single-gene
      mutations in key cellular pathways that regulate environmental sensing, and the
      response to stress, have been identified that prolong life span across evolution
      from yeast to mammals. These genetic manipulations also correlate with a delay in
      the onset of tissue and organismal dysfunction. While the molecular genetics of
      aging will remain a prosperous and attractive area of research in biogerontology,
      we are moving towards an era defined by the search for therapeutic drugs that
      promote healthy aging. Translational biogerontology will require incorporation of
      both therapeutic and pharmacological concepts. The use of model organisms will
      remain central to the quest for drug discovery, but as we uncover molecular
      processes regulated by repurposed drugs and polypharmacy, studies of
      pharmacodynamics and pharmacokinetics, drug-drug interactions, drug toxicity, and
      therapeutic index will slowly become more prevalent in aging research. As we move
      from genetics to pharmacology and therapeutics, studies will not only require
      demonstration of life span extension and an underlying molecular mechanism, but
      also the translational relevance for human health and disease prevention. 

PMID- 26296934
TI  - MicroRNAs: tools of mechanistic insights and biological therapeutics discovery
      for the rare neurogenetic syndrome Lesch-Nyhan disease (LND).
AB  - MicroRNAs (miRNAs) are small regulatory RNAs that modulate the translation of
      mRNA. They have emerged over the past few years as indispensable entities in the
      transcriptional regulation of genes. Their discovery has added additional layers
      of complexity to regulatory networks that control cellular homeostasis. Also,
      their dysregulated pattern of expression is now well demonstrated in myriad
      diseases and pathogenic processes. In the current review, we highlight the role
      of miRNAs in Lesch-Nyhan disease (LND), a rare neurogenetic syndrome caused by
      mutations in the purine metabolic gene encoding the hypoxanthine-guanine
      phosphoribosyltransferase (HPRT) enzyme. We describe how experimental and
      biocomputational approaches have helped to unravel genetic and signaling pathways
      that provide mechanistic understanding of some of the molecular and cellular
      basis of this ill-defined neurogenetic disorder. Through miRNA-based target
      predictions, we have identified signaling pathways that may be of significance in
      guiding biological therapeutic discovery for this incurable neurological
      disorder. We also propose a model to explain how a gene such as HPRT, mostly
      known for its housekeeping metabolic functions, can have pleiotropic effects on
      disparate genes and signal transduction pathways. Our hypothetical model suggests
      that HPRT mRNA transcripts may be acting as competitive endogenous RNAs (ceRNAs)
      intertwined in multiregulatory cross talk between key neural transcripts and
      miRNAs. Overall, this approach of using miRNA-based genomic approaches to
      elucidate the molecular and cellular basis of LND and guide biological target
      identification might be applicable to other ill-defined rare inborn-error
      metabolic diseases. 

PMID- 26296935
TI  - Small RNAs in bacteria and archaea: who they are, what they do, and how they do
      it.
AB  - Small RNAs are ubiquitously present regulators in all kingdoms of life. Most
      bacterial and archaeal small RNAs (sRNAs) act by antisense mechanisms on multiple
      target mRNAs, thereby globally affecting essentially any conceivable trait-stress
      responses, adaptive metabolic changes, virulence etc. The sRNAs display many
      distinct mechanisms of action, most of them through effects on target mRNA
      translation and/or stability, and helper proteins like Hfq often play key roles.
      Recent data highlight the interplay between posttranscriptional control by sRNAs
      and transcription factor-mediated transcriptional control, and cross talk through
      mutual regulation of regulators. Based on the properties that distinguish sRNA
      type from transcription factors-type control, we begin to glimpse why sRNAs have
      evolved as a second, essential layer of gene regulation. This review will discuss
      the prevalence of sRNAs, who they are, what biological roles they play, and how
      they carry out their functions. 

PMID- 26296936
TI  - Copy number variations in multiple sclerosis and neuromyelitis optica.
AB  - OBJECTIVE: To clarify the potential association of copy number variations (CNVs)
      with multiple sclerosis (MS) and neuromyelitis optica (NMO) in Japanese cases.
      METHODS: Genome-wide association analyses of CNVs among 277 MS patients, 135
      NMO/NMO spectrum disorder (NMOSD) patients, and 288 healthy individuals as a
      discovery cohort, and among 296 MS patients, 76 NMO/NMOSD patients, and 790
      healthy individuals as a replication cohort were performed using high-density
      single nucleotide polymorphism microarrays. RESULTS: A series of discovery and
      replication studies revealed that most identified CNVs were 5 to 50kb deletions
      at particular T cell receptor (TCR) gamma and alpha loci regions. Among these
      CNVs, a TCR gamma locus deletion was found in 16.40% of MS patients (p = 2.44E
      40, odds ratio [OR] = 52.6), and deletion at the TCR alpha locus was found in
      17.28% of MS patients (p = 1.70E-31, OR = 13.0) and 13.27% of NMO/NMOSD patients
      (p = 5.79E-20, OR = 54.6). These CNVs were observed in peripheral blood T-cell
      subsets only, suggesting the CNVs were somatically acquired. NMO/NMOSD patients
      carrying the CNV tended to be seronegative for anti-aquaporin-4 antibody or had
      significantly lower titers than those without CNV. INTERPRETATION: Deletion-type
      CNVs at specific TCR loci regions contribute to MS and NMO susceptibility.

PMID- 26296937
TI  - Development of a heart valve model surface for optimization of surface
      modifications.
AB  - Current bioprosthetic valve replacements (BPVs) are susceptible to myriad
      complications, including calcification and thrombosis; however, recent research
      has explored surface modifications to encourage re-endothelialization of the
      tissue, preventing unwanted blood-tissue interactions. A bioprosthetic valve
      surface model (BVSM) was developed to facilitate rapid in vitro optimization of
      surface modification techniques for BPVs. The BVSM was manufactured by
      photopolymerization of PEGDA and collagen type I and subsequent addition of amine
      rich peptide to provide reactive sites for surface modification. This BVSM mimics
      surface mechanical properties of bioprosthetic valve tissue, as measured by
      micropipette aspiration. The BVSM successfully mimics the latent toxic effects of
      glutaraldehyde fixation, as shown through MTT assay results. Amine content,
      assessed by XPS, was shown to be significantly lower in the BVSM than unfixed
      tissue. However, incubation of the surface with amine-reactive NHS-PEG-Cy5
      revealed even coverage of the BVSM surface, suggesting that there exists
      sufficient surface reactive groups to anchor surface modifications, and that
      translation of the modification process to tissue will yield more complete
      modification of the BPV surface. These results indicate successful construction
      of a BVSM that mimics essential properties of bioprosthetic valve tissue and its
      usefulness for rapid in vitro optimization of surface modification methods for
      endothelialization. STATEMENT OF SIGNIFICANCE: Current bioprosthetic valve
      replacements are susceptible to many complications, including calcification and
      thrombosis; however, recent research has explored surface modifications to
      encourage the integration of the replacement with the native tissue, which would
      prevent unwanted blood-tissue interactions. However, methods to analyze and
      optimize such modifications are limited by the complex surface topography,
      individual variability, and opacity of native tissue. Thus, we have developed a
      novel bioprosthetic valve tissue model (BVM) which mimics the important features
      of the bioprosthetic valve tissue and serves as a platform for rapid optimization
      and testing of surface modification strategies for tissue valves. Thus, the BVM
      will provide a needed platform to support rapid improvement of clinically
      available cardiovascular implants.

PMID- 26296938
TI  - Exposure to D2-like dopamine receptor agonists inhibits swimming in Daphnia
      magna.
AB  - Daphnia are freshwater crustaceans that have been used for decades in
      ecotoxicology research. Despite the important role that Daphnia have played in
      environmental toxicology studies, very little is known about the neurobiology of
      Daphnia. Although many studies have investigated the swimming movements of these
      "water fleas", few studies have examined the underlying neurochemical basis for
      these movements. To characterize the locomotor effect of drugs in Daphnia, a two
      dimensional video imaging tool was developed and animal tracking was performed
      with freely available software, CTRAX. Due to the central role that dopamine
      plays in the movement of animals, we sought to determine the role of dopamine
      receptor signaling in Daphnia movement by characterizing the effect of ten drugs
      that are agonists or antagonists of dopamine receptors. At 1, 2, and 6h of
      treatment with a 10MUM drug, several dopamine receptor agonists with documented
      effects on the D2-like class of receptors decreased the movement. Further, we
      determined behavioral inhibition values (IC50) at 1h of treatment for (1R,3S)-1
      (aminomethyl)-3-phenyl-3,4-dihydro-1H-isochromene-5,6-diol (A68930) to be 1.4MUM
      and for bromocriptine to be 6.6MUM. This study describes a new method to study
      Daphnia swimming and establishes this organism as a useful model for studies of
      dopaminergic signaling. Specifically, this study shows that a dopamine receptor
      signaling pathway, mediated by putative D2-like receptors, is involved in the
      control of Daphnia swimming behavior. Due to its ease of use and its rich motor
      program we propose that Daphnia should be considered for future studies of
      dopamine neuron toxicity and protection. 

PMID- 26296939
TI  - Neonatal quinpirole treatment produces prepulse inhibition deficits in adult male
      and female rats.
AB  - We have shown that repeated neonatal quinpirole (QUIN; a dopamine D2-like
      receptor agonist) treatment in rats produces long-lasting supersensitization of
      dopamine D2 receptors that persists into adulthood but without producing a change
      in receptor number. The current study was designed to analyze the effects of
      neonatal QUIN on auditory sensorimotor gating as measured through prepulse
      inhibition (PPI). Male and female Sprague-Dawley rats were neonatally treated
      with QUIN (1mg/kg) or saline from postnatal days (P)1-21. At P60, the number of
      yawns was recorded for a 1h period in response to an acute QUIN (1mg/kg)
      injection as yawning is a D2-like receptor mediated behavioral event. Five days
      later, rats began (PPI) behavioral testing in two phases. In phase I, three
      different prepulse intensities (73, 76, and 82dB) were administered 100-ms before
      a 115dB pulse on 10 consecutive days. In phase II, three different interstimulus
      intervals (ISI; 50, 100, and 150ms) were inserted between the 73 or 76dB prepulse
      and 115dB pulse over 10 consecutive days of testing. A PPI probe trial was
      administered at the end of each phase after an acute 100MUg/kgi.p. injection of
      QUIN to all animals. Replicating previous work, neonatal QUIN enhanced yawning
      compared to controls, verifying D2 receptor supersensitization. Regarding PPI,
      neonatal QUIN resulted in deficits across both phases of testing persistent
      across all testing days. Probe trial results revealed that acute QUIN treatment
      resulted in more robust PPI deficits in neonatal QUIN animals, although this
      deficit was related to prepulse intensity and ISI. These findings provide
      evidence that neonatal QUIN treatment results in deficits of auditory
      sensorimotor gating in adulthood as measured through PPI. 

PMID- 26296940
TI  - Message from the editor in chief.

PMID- 26296942
TI  - [Erratum to: Osteogenesis imperfecta].

PMID- 26296941
TI  - LOX-1 gene variants and maternal levels of plasma oxidized LDL and
      malondialdehyde in patients with gestational diabetes mellitus.
AB  - PURPOSE: The aim of this study was to investigate the relationships between the
      maternal levels of oxidized LDL (ox-LDL), lipid peroxidation marker
      malondialdehyde (MDA) and LOX-1 3'UTR188C/T and K167N single nucleotide
      polymorphisms in pregnant Turkish women with gestational diabetes mellitus (GDM).
      METHODS: 116 pregnant women with GDM and 120 healthy pregnant women from the same
      geographic region were included in the study. Polymerase chain reaction-based
      restriction analysis was used to identify 3'UTR188C/T and K167N polymorphisms of
      the LOX-1 gene. Plasma ox-LDL and MDA levels were determined by enzyme-linked
      immunosorbent assay and spectrophotometric method in all study subjects,
      respectively. RESULTS: Our results indicated that the distribution of the LOX-1
      3'UTR188C/T and K167N genotypes and alleles did not differ significantly among
      subjects with or without GDM (p > 0.05). TT and NN genotype carriers are
      associated with some glucose metabolism parameters (p < 0.05). There were no
      significant differences among plasma ox-LDL and MDA levels with regard to LOX-1
      3'UTR188C/T and K167N polymorphisms in GDM group and control subjects (p > 0.05).
      According to the combined genotype analysis of LOX-1 3'UTR 188 TT and K167N NN
      polymorphisms, plasma MDA and ox-LDL levels were significantly different between
      women with GDM and healthy subjects either with or without combined TT/NN
      genotype carriers (p < 0.001). CONCLUSIONS: According to our results, ox-LDL and
      MDA levels were increased in GDM pregnant women and healthy pregnant women either
      with or without combined TT/NN genotype carriers, for our Turkish sample, these
      genotype carriers appear to be related with increased oxidative stress in
      patients with GDM.

PMID- 26296943
TI  - Caenispirillum deserti sp. nov., a spheroplast-forming bacterium isolated from a
      salt desert.
AB  - A Gram-stain-negative, vibrio-shaped, spheroplast-forming, motile, aerobic
      bacterium was isolated from the soil of a salt desert in Kutch, Gujarat, India.
      The strain, designated JC232(T), was oxidase- and catalase-positive. 16S rRNA
      gene sequence analysis indicated that strain JC232(T) was a member of the genus
      Caenispirillum and was related most closely to Caenispirillum salinarum AK4(T)
      (98.9% similarity) and Caenispirillum bisanense K92(T) (96.8%). Genome
      relatedness based on DNA-DNA hybridization of strain JC232(T) with the type
      strains of closely related species was less than 40%. The DNA G+C content of
      strain JC232(T) was 70 mol%. Phosphatidylglycerol, phosphatidylethanolamine,
      phosphotidylcholine, diphosphatidylglycerol, two unidentified amino lipids (AL1
      and 2) and four unidentified lipids (UL1-4) were the polar lipids of strain
      JC232(T). C18 : 1omega7c/C18 : 1omega6c, C16 : 0 and C16 : 1omega7c/C16 :
      1omega6c were the major (>15%) fatty acids of strain JC232(T), with minor amounts
      of C12 : 0, C14 : 0 3-OH/iso-C16 : 0 I, C18 : 1 2-OH, C18 : 0, C16 : 0 3-OH and
      C19 : 0cycloomega8c. Although strain JC232(T) shared the predominant ubiquinone
      system (Q10) with the type strains of C. salinarum and C. bisanense, it differed
      from the latter in polar lipid profile, NaCl growth range and other
      phenotypic/physiological properties. On the basis of morphological,
      physiological, genotypic, phylogenetic and chemotaxonomic analyses, strain
      JC232(T) is considered to represent a novel species of the genus Caenispirillum,
      for which the name Caenispirillum deserti sp. nov. is proposed. The type strain
      is JC232(T) ( = KCTC 42064(T) = NBRC 110150(T)).

PMID- 26296944
TI  - Fungal Peritonitis Due to Fusarium solani Species Complex Sequential Isolates
      Identified with DNA Sequencing in a Kidney Transplant Recipient in Brazil.
AB  - Fungal peritonitis is a rare serious complication most commonly observed in
      immunocompromised patients under peritoneal dialysis. Nevertheless, this clinical
      condition is more difficult to treat than bacterial peritonitis. Bacterial
      peritonitis followed by the use of antibiotics is the main risk factor for
      developing fungal peritonitis. Candida spp. are more frequently isolated, and the
      isolation of filamentous fungi is only occasional. Here we describe a case of
      Fusarium solani species complex peritonitis associated with bacterial peritonitis
      in a female kidney transplant recipient with previous history of nephrotic
      syndrome. The patient has had Enterobacter sp. endocarditis and was hypertensive
      and diabetic. Two sequential isolates of F. solani were recovered from cultures
      and identified with different molecular techniques. She was successfully treated
      with 50 mg daily amphotericin B for 4 weeks.

PMID- 26296945
TI  - Radiation induced heart disease: Pathogenesis, management and review literature.
AB  - Radiation therapy (RT) is a very important part of multimodality cancer therapy.
      Addition of RT improves survival in many cancers, but there are some
      accompaniments of radiation. One of them is radiation induced heart disease
      (RIHD). RT for mediastinal lymphoma, breast, lung and oesophageal cancer is
      associated with the development of RIHD. The problem can be intensified with the
      addition of chemotherapy. Therapeutic modalities for RIHD are the same as in the
      non-irradiated population. However, surgery may be difficult in the irradiated
      patients. The long latent period is the reason why RIHD is not extensively
      studied. Survival of cancer patients has improved over past few decades, so RIHD
      is a growing concern especially in younger patients. In this review article, we
      have discussed the pathogenesis, clinical manifestation and management of RIHD
      along with impact of chemotherapeutic agents. 

PMID- 26296947
TI  - Modafinil does enhance cognition, review finds.

PMID- 26296946
TI  - Transforming growth factor-beta signaling enhancement by long-term exposure to
      hypoxia in a tumor microenvironment composed of Lewis lung carcinoma cells.
AB  - Transforming growth factor-beta (TGF-beta) is a potent growth inhibitor in normal
      epithelial cells. However, a number of malignant tumors produce excessive amounts
      of TGF-beta, which affects the tumor-associated microenvironment by furthering
      the progression of tumorigenicity. Although it is known that the tumor-associated
      microenvironment often becomes hypoxic, how hypoxia influences TGF-beta signaling
      in this microenvironment is unknown. We investigated whether TGF-beta signaling
      is influenced by long-term exposure to hypoxia in Lewis lung carcinoma (LLC)
      cells. When the cells were exposed to hypoxia for more than 10 days, their
      morphology was remarkably changed to a spindle shape, and TGF-beta-induced Smad2
      phosphorylation was enhanced. Concomitantly, TGF-beta-induced transcriptional
      activity was augmented under hypoxia, although TGF-beta did not influence the
      activity of a hypoxia-responsive reporter. Consistently, hypoxia influenced the
      expression of several TGF-beta target genes. Interestingly, the expressions of
      TGF-beta type I receptor (TbetaRI), also termed activin receptor like kinase-5
      (ALK5), and TGF-beta1 were increased under the hypoxic condition. When we
      monitored the hypoxia-inducible factor-1 (HIF-1) transcriptional activity by use
      of green fluorescent protein governed by the hypoxia-responsive element in LLC
      cells transplanted into mice, TGF-beta-induced Smad2 phosphorylation was
      upregulated in vivo. Our results demonstrate that long-term exposure to hypoxia
      might alter responsiveness to TGF-beta signaling and affected the malignancy of
      LLC cells. 

PMID- 26296948
TI  - Balancing the energy equation for healthy kidneys.
AB  - The high-energy requirement of the kidney and the importance of energy metabolism
      in renal physiology has been appreciated for decades, but only recently has there
      emerged a strong link between impaired renal energy metabolism and chronic kidney
      disease (CKD). The mechanisms underlying the association between changes in
      energy metabolism and progression of CKD, however, remain poorly understood. A
      new study from Qiu and colleagues reported in the Journal of Pathology has
      advanced this understanding by showing that, after renal injury, the energy
      sensor AMPK inhibits epithelial-mesenchymal transition and inflammation,
      processes important in the pathogenesis of CKD. Furthermore, this study
      identifies an interaction between AMPK and CK2beta as an important mechanism in
      the anti-fibrotic effect. CK2beta has previously been shown to interact with
      STK11 (also known as LKB1) to regulate cellular polarity. These findings are
      consistent with the known roles of the LKB1-AMPK pathway in sustaining cellular
      energy homeostasis and epithelial cell polarity, and add to growing evidence
      linking the suppression of energy metabolism to CKD. They emphasize the
      importance of energy metabolism in general and the LKB1-AMPK axis in particular
      as key investigational and therapeutic targets in the battle against CKD.

PMID- 26296949
TI  - Process for Managing and Optimizing Radiology Work Flow in the Electronic Heath
      Record Environment.
AB  - Electronic health record (EHR) implementation has dramatically impacted all
      facets of radiology workflow. Many departments find themselves unprepared for the
      multiple issues that surface following EHR deployment and the ongoing need for
      workflow optimization. This paper reviews the structure and processes utilized by
      the team, developed at the University of Colorado Hospital to evaluate,
      prioritize, and implement requests for workflow repairs and improvements within
      the EHR. The evolution of this team as the academic hospital formed a health
      system with two community hospital sites is also described. This structure may
      serve as a useful template for others considering EHR deployment or struggling to
      manage radiology workflow within an existing EHR environment. 

PMID- 26296950
TI  - Bubble continuous positive airway pressure for children with severe pneumonia and
      hypoxaemia in Bangladesh: an open, randomised controlled trial.
AB  - BACKGROUND: In developing countries, mortality in children with very severe
      pneumonia is high, even with the provision of appropriate antibiotics, standard
      oxygen therapy, and other supportive care. We assessed whether oxygen therapy
      delivered by bubble continuous positive airway pressure (CPAP) improved outcomes
      compared with standard low-flow and high-flow oxygen therapies. METHODS: This
      open, randomised, controlled trial took place in Dhaka Hospital of the
      International Centre for Diarrhoeal Disease Research, Bangladesh. We randomly
      assigned children younger than 5 years with severe pneumonia and hypoxaemia to
      receive oxygen therapy by either bubble CPAP (5 L/min starting at a CPAP level of
      5 cm H2O), standard low-flow nasal cannula (2 L/min), or high-flow nasal cannula
      (2 L/kg per min up to the maximum of 12 L/min). Randomisation was done with use
      of the permuted block methods (block size of 15 patients) and Fisher and Yates
      tables of random permutations. The primary outcome was treatment failure (ie,
      clinical failure, intubation and mechanical ventilation, death, or termination of
      hospital stay against medical advice) after more than 1 h of treatment. Primary
      and safety analyses were by intention to treat. We did two interim analyses and
      stopped the trial after the second interim analysis on Aug 3, 2013, as directed
      by the data safety and monitoring board. This trial is registered at
      ClinicalTrials.gov, number NCT01396759. FINDINGS: Between Aug 4, 2011, and July
      17, 2013, 225 eligible children were recruited. We randomly allocated 79 (35%)
      children to receive oxygen therapy by bubble CPAP, 67 (30%) to low-flow oxygen
      therapy, and 79 (35%) to high-flow oxygen therapy. Treatment failed for 31 (14%)
      children, of whom five (6%) had received bubble CPAP, 16 (24%) had received low
      flow oxygen therapy, and ten (13%) had received high-flow oxygen therapy.
      Significantly fewer children in the bubble CPAP group had treatment failure than
      in the low-flow oxygen therapy group (relative risk [RR] 0.27, 99.7% CI 0.07
      0.99; p=0.0026). No difference in treatment failure was noted between patients in
      the bubble CPAP and those in the high-flow oxygen therapy group (RR 0.50, 99.7%
      0.11-2.29; p=0.175). 23 (10%) children died. Three (4%) children died in the
      bubble CPAP group, ten (15%) children died in the low-flow oxygen therapy group,
      and ten (13%) children died in the high-flow oxygen therapy group. Children who
      received oxygen by bubble CPAP had significantly lower rates of death than the
      children who received oxygen by low-flow oxygen therapy (RR 0.25, 95% CI 0.07
      0.89; p=0.022). INTERPRETATION: Oxygen therapy delivered by bubble CPAP improved
      outcomes in Bangladeshi children with very severe pneumonia and hypoxaemia
      compared with standard low-flow oxygen therapy. Use of bubble CPAP oxygen therapy
      could have a large effect in hospitals in developing countries where the only
      respiratory support for severe childhood pneumonia and hypoxaemia is low-flow
      oxygen therapy. The trial was stopped early because of higher mortality in the
      low-flow oxygen group than in the bubble CPAP group, and we acknowledge that the
      early cessation of the trial reduces the certainty of the findings. Further
      research is needed to test the feasibility of scaling up bubble CPAP in district
      hospitals and to improve bubble CPAP delivery technology. FUNDING: International
      Centre for Diarrhoeal Disease Research, Bangladesh, and Centre for International
      Child Health, University of Melbourne.

PMID- 26296951
TI  - Neuroinflammatory pathways in anxiety, posttraumatic stress, and obsessive
      compulsive disorders.
AB  - As prevalence of anxiety, posttraumatic stress, and obsessive compulsive
      disorders continue to rise worldwide, increasing focus has been placed on immune
      mediated theories in understanding the underlying mechanisms of these disorders.
      Associations between the dysregulation of the hypothalamic-pituitary-adrenal
      (HPA) axis and these disorders have been recognized in the scientific literature,
      specifically in regard to cortisol levels, as well as changes in pro- and anti
      inflammatory cytokines. The present commentary will systematically assess the
      scientific literature within the past decade in regard to the
      psychoneuroimmunology of anxiety, posttraumatic stress, and obsessive compulsive
      disorders. Understanding the mechanisms of these disorders is essential in order
      to determine efficacious and targeted treatment strategies, which may lead to
      substantial improvements in overall functioning, as well as significant decreases
      in societal and economic burden. 

PMID- 26296952
TI  - Safety and activity of RRx-001 in patients with advanced cancer: a first-in
      human, open-label, dose-escalation phase 1 study.
AB  - BACKGROUND: Epigenetic alterations have been strongly associated with tumour
      formation and resistance to chemotherapeutic drugs, and epigenetic modifications
      are an attractive target in cancer research. RRx-001 is activated by hypoxia and
      induces the generation of reactive oxygen and nitrogen species that can
      epigenetically modulate DNA methylation, histone deacetylation, and lysine
      demethylation. The aim of this phase 1 study was to assess the safety,
      tolerability, and pharmacokinetics of RRx-001. METHODS: In this open-label, dose
      escalation, phase 1 study, we recruited adult patients (aged >18 years) with
      histologically or cytologically confirmed diagnosis of advanced, malignant,
      incurable solid tumours from University of California at San Diego, CA, USA, and
      Sarah Cannon Research Institute, Nashville, TN, USA. Key eligibility criteria
      included evaluable disease, Eastern Cooperative Group performance status of 2 or
      less, an estimated life expectancy of at least 12 weeks, adequate laboratory
      parameters, discontinuation of all previous antineoplastic therapies at least 6
      weeks before intervention, and no residual side-effects from previous therapies.
      Patients were assigned to receive intravenous infusions of RRx-001 at increasing
      doses (10 mg/m(2), 16.7 mg/m(2), 24.6 mg/m(2), 33 mg/m(2), 55 mg/m(2), and 83
      mg/m(2)) either once or twice-weekly for at least 4 weeks, with at least three
      patients per dose cohort and allowing a 2-week observation period before dose
      escalation. Samples for safety and pharmacokinetics analysis, including standard
      chemistry and haematological panels, were taken on each treatment day. The
      primary objective was to assess safety, tolerability, and dose-limiting toxic
      effects of RRx-001, to determine single-dose pharmacokinetics, and to identify a
      recommended dose for phase 2 trials. All analyses were done per protocol. Accrual
      is complete and follow-up is still on-going. This trial is registered with
      ClinicalTrials.gov, number NCT01359982. FINDINGS: Between Oct 10, 2011, and March
      18, 2013, we enrolled 25 patients and treated six patients in the 10 mg/m(2)
      cohort, three patients in the 16.7 mg/m(2) cohort, three patients in the 24.6
      mg/m(2) cohort, four patients in the 33 mg/m(2) cohort, three patients in the 55
      mg/m(2), and six patients in the 83 mg/m(2) cohort. Pain at the injection site,
      mostly grade 1 and grade 2, was the most common adverse event related to
      treatment, experienced by 21 (84%) patients. Other common drug-related adverse
      events included arm swelling or oedema (eight [32%] patients), and vein hardening
      (seven [28%] patients). No dose-limiting toxicities were observed. Time
      constraints related to management of infusion pain from RRx-001 resulted in a
      maximally feasible dose of 83 mg/m(2). Of the 21 evaluable patients, one (5%)
      patient had a partial response, 14 (67%) patients had stable disease, and six
      (29%) patients had progressive disease; all responses were across a variety of
      tumour types. Four patients who had received RRx-001 were subsequently
      rechallenged with a treatment that they had become refractory to; all four
      responded to the rechallenge. INTERPRETATION: RRx-001 is a well-tolerated novel
      compound without clinically significant toxic effects at the tested doses.
      Preliminary evidence of activity is promising and, on the basis of all findings,
      a dose of 16.7 mg/m(2) was recommended as the targeted dose for phase 2 trials.
      FUNDING: EpicentRx (formerly RadioRx).

PMID- 26296953
TI  - Epigenetic approaches to overcoming chemotherapy resistance.

PMID- 26296955
TI  - Guadecitabine for AML and MDS: hype or hope?

PMID- 26296954
TI  - Safety and tolerability of guadecitabine (SGI-110) in patients with
      myelodysplastic syndrome and acute myeloid leukaemia: a multicentre, randomised,
      dose-escalation phase 1 study.
AB  - BACKGROUND: Hypomethylating agents are used to treat cancers driven by aberrant
      DNA methylation, but their short half-life might limit their activity,
      particularly in patients with less proliferative diseases. Guadecitabine (SGI
      110) is a novel hypomethylating dinucleotide of decitabine and deoxyguanosine
      resistant to degradation by cytidine deaminase. We aimed to assess the safety and
      clinical activity of subcutaneously given guadecitabine in patients with acute
      myeloid leukaemia or myelodysplastic syndrome. METHODS: In this multicentre, open
      label, phase 1 study, patients from nine North American medical centres with
      myelodysplastic syndrome or acute myeloid leukaemia that was refractory to or had
      relapsed after standard treatment were randomly assigned (1:1) to receive
      subcutaneous guadecitabine, either once-daily for 5 consecutive days (daily * 5),
      or once-weekly for 3 weeks, in a 28-day treatment cycle. Patients were stratified
      by disease. A 3 + 3 dose-escalation design was used in which we treated patients
      with guadecitabine doses of 3-125 mg/m(2) in separate dose-escalation cohorts. A
      twice-weekly treatment schedule was added to the study after a protocol
      amendment. The primary objective was to assess safety and tolerability of
      guadecitabine, determine the maximum tolerated and biologically effective dose,
      and identify the recommended phase 2 dose of guadecitabine. Safety analyses
      included all patients who received at least one dose of guadecitabine.
      Pharmacokinetic and pharmacodynamic analyses to determine the biologically
      effective dose included all patients for whom samples were available. This study
      is registered with ClinicalTrials.gov, number NCT01261312. FINDINGS: Between Jan
      4, 2011, and April 11, 2014, we enrolled and treated 93 patients: 35 patients
      with acute myeloid leukaemia and nine patients with myelodysplastic syndrome in
      the daily * 5 dose-escalation cohorts, 28 patients with acute myeloid leukaemia
      and six patients with myelodysplastic syndrome in the once-weekly dose-escalation
      cohorts, and 11 patients with acute myeloid leukaemia and four patients with
      myelodysplastic syndrome in the twice-weekly dose-escalation cohorts. The most
      common grade 3 or higher adverse events were febrile neutropenia (38 [41%] of 93
      patients), pneumonia (27 [29%] of 93 patients), thrombocytopenia (23 [25%] of 93
      patients), anaemia (23 [25%] of 93 patients), and sepsis (16 [17%] of 93
      patients). The most common serious adverse events were febrile neutropenia (29
      [31%] of 93 patients), pneumonia (26 [28%] of 93 patients), and sepsis (16 [17%]
      of 93 patients). Six of the 74 patients with acute myeloid leukaemia and six of
      the 19 patients with myelodysplastic syndrome had a clinical response to
      treatment. Two dose-limiting toxicities were noted in patients with
      myelodysplastic syndrome at 125 mg/m(2) daily * 5, thus the maximum tolerated
      dose in patients with myelodysplastic syndrome was 90 mg/m(2) daily * 5. The
      maximum tolerated dose was not reached in patients with acute myeloid leukaemia.
      Potent dose-related DNA demethylation occurred on the daily * 5 regimen, reaching
      a plateau at 60 mg/m(2) (designated as the biologically effective dose).
      INTERPRETATION: Guadecitabine given subcutaneously at 60 mg/m(2) daily * 5 is
      well tolerated and is clinically and biologically active in patients with
      myelodysplastic syndrome and acute myeloid leukaemia. Guadecitabine 60 mg/m(2)
      daily * 5 is the recommended phase 2 dose, and these findings warrant further
      phase 2 studies. FUNDING: Astex Pharmaceuticals, Stand Up To Cancer.

PMID- 26296956
TI  - Ca(2+) -regulated and diurnal rhythm-regulated Na(+) /Ca(2+) exchanger AtNCL
      affects flowering time and auxin signalling in Arabidopsis.
AB  - Calcium (Ca(2+) ) is vital for plant growth, development, hormone response and
      adaptation to environmental stresses, yet the mechanisms regulating plant
      cytosolic Ca(2+) homeostasis are not fully understood. Here, we characterize an
      Arabidopsis Ca(2+) -regulated Na(+) /Ca(2+) exchanger AtNCL that regulates Ca(2+)
      and multiple physiological processes. AtNCL was localized to the tonoplast in
      yeast and plant cells. AtNCL appeared to mediate sodium (Na(+) ) vacuolar
      sequestration and meanwhile Ca(2+) release. The EF-hand domains within AtNCL
      regulated Ca(2+) binding and transport of Ca(2+) and Na(+) . Plants with
      diminished AtNCL expression were more tolerant to high CaCl2 but more sensitive
      to both NaCl and auxin; heightened expression of AtNCL rendered plants more
      sensitive to CaCl2 but tolerant to NaCl. AtNCL expression appeared to be
      regulated by the diurnal rhythm and suppressed by auxin. DR5::GUS expression and
      root responses to auxin were altered in AtNCL mutants. The auxin-induced
      suppression of AtNCL was attenuated in SLR/IAA14 and ARF6/8 mutants. The mutants
      with altered AtNCL expression also altered flowering time and FT and CO
      expression; FT may mediate AtNCL-regulated flowering time change. Therefore,
      AtNCL is a vacuolar Ca(2+) -regulated Na(+) /Ca(2+) exchanger that regulates
      auxin responses and flowering time. 

PMID- 26296958
TI  - One-and-done: Do left ventricular assist device patients on the transplant list
      really need frequent right heart catheterization assessments for pulmonary
      hypertension?

PMID- 26296959
TI  - The influence of institutional volume on the incidence of complications and their
      effect on mortality after heart transplantation.
AB  - BACKGROUND: The aim of this study was to determine whether institutional volume
      influenced the effect of postoperative complications on short-term and long-term
      survival after orthotopic heart transplantation (OHT). METHODS: The United
      Network for Organ Sharing database was queried for adult patients (aged >=18
      years) undergoing OHT between 2000 and 2010. Average institutional volume was
      calculated during the study period and modeled as a categoric and as a continuous
      variable. Postoperative complications included rejection, dialysis dependence,
      infection, stroke, reoperation, and a composite event. Kaplan-Meier estimates and
      Cox regression modeling were performed for each complication to categorize the
      unadjusted and adjusted influence of institutional volume on survival. RESULTS:
      The analysis included 19,849 OHT recipients who were stratified into low-volume
      (<=14.5 per year), intermediate-volume (14.5-26.5 per year), and high-volume
      (>26.5 per year) tertiles. The overall incidences of postoperative complications
      were 10.2% for rejection, 7.8% for dialysis dependence, 12.0% for reoperation,
      24.1% for infection, and 2.3% for stroke. Recipients in low-volume institutions
      experienced more complications after OHT than high-volume institutions (43.4% vs
      36.2%; p < 0.001). Survival after the composite complication outcome was
      significantly worse at 90 days, 1 year, and 5 years in the low-volume cohort.
      After risk adjustment, low institutional volume (when modeled as a continuous and
      as a categoric variable) was also independently predictive of mortality at each
      time point. As expected, survival at 5 years in patients without a postoperative
      complication (81%; 95 confidence interval [CI], 80.0%-82.8%) was statistically
      greater (p < 0.001) than those with 1 (72.8%; 95% CI, 69.9%-75.5%), 2 (59.8%; 95%
      CI, 54.4%-64.8%), or 3 (39.9%; 95% CI, 31.6%-48.2%) complications. CONCLUSIONS:
      Postoperative complications after OHT have a greater incidence and effect on
      short-term and long-term survival at low-volume institutions. Accordingly, best
      practice guidelines established at high-volume institutions could better equip
      lower-volume hospitals to manage these events in hopes of optimizing transplant
      outcomes.

PMID- 26296961
TI  - In people with atrial fibrillation receiving antithrombotics, short-term non
      steroidal anti-inflammatory drug exposure increases risk of serious bleeding.

PMID- 26296960
TI  - Predictors of 30-day post-transplant mortality in patients bridged to
      transplantation with continuous-flow left ventricular assist devices--An analysis
      of the International Society for Heart and Lung Transplantation Transplant
      Registry.
AB  - BACKGROUND: Continuous-flow (CF) left ventricular assist devices (LVADs) are
      standard of care for bridging patients to cardiac transplantation. However,
      existing data about preoperative factors influencing early post-transplant
      survival in these patients are limited. We sought to determine risk factors for
      mortality using a large international database. METHODS: All patients in the
      International Society for Heart and Lung Transplantation Transplant Registry who
      were bridged to transplantation with CF LVADs between June 2008 and June 2012
      were included. Risk factors for mortality within 30 days of transplant were
      identified. Statistical analysis included multivariable analysis and Kaplan-Meier
      survival analysis. RESULTS: During the study period, 2,152 patients with CF LVADs
      underwent heart transplantation. Post-transplant survival was 95.5% at 30 days.
      Risk factors for mortality during this window included ventilator support at
      transplant (hazard ratio [HR] = 5.00, 95% confidence interval [CI] = 1.51-16.58),
      female recipient/male donor (compared with all other combinations, HR = 3.29, 95%
      CI = 1.90-5.72), history of hemodialysis (HR = 2.51, 95% CI = 1.14-5.51), and
      history of coronary bypass grafting (HR = 1.89, 95% CI = 1.19-3.00). Increasing
      recipient age (p = 0.002), body mass index (p = 0.002), creatinine (p = 0.004),
      and total bilirubin (p < 0.001) also were associated with an increase in
      mortality. CONCLUSIONS: In patients supported with CF LVADs, risk factors for
      early mortality can be identified before transplant, including ventilator
      support, female recipient/male donor, increasing recipient age, and body mass
      index. Despite the inherent complexities of a reoperative surgery, patients
      bridged to transplant with CF LVADs have excellent peri-operative survival.

PMID- 26296962
TI  - [Changing and follow-up of silicone gel-filled breast implants: Multicentric,
      retrospective study about 130 rupture cases].
AB  - SUBJECT: A recent report from "Agence Nationale de securite du medicament et des
      produits de sante" (ANSM) assesses the rupture of silicone gel breast implants
      without proposing rules for follow-up and replacement of implants. OBJECTIVE: To
      demonstrate that systematic follow-up surveillance of silicone breast implants
      could improve early diagnosis of ruptures; to propose a surveillance protocol
      based on the findings. MATERIALS AND METHODS: This is a multicentric,
      retrospective study which reports cases of ruptured silicone gel breast implants
      from January 2006 to June 2014. Using Case-notes from ANSM and quotations from
      CCAM certificates, 130cases were gathered from 6 centers. RESULTS: The average
      time between implantation and the diagnosis of ruptures was 9.24 years (+/-
      6.19). Forty cases of ruptured implants (30.8%) originated from original
      reconstruction or symmetrisation in the context of a breast carcinoma; and 90
      (69.2%) originated from augmentation mammaplasty. The average length in
      reconstructive group was 6.97 years (+/- 3.33). The difference in the lifetime of
      the implants between both groups was statistically significant (P = 0.0291). A
      clinical abnormality led to an imaging assessment in only 19.7% of cases; rupture
      was thus mainly discovered incidentally either during a systematic breast
      screening (59.8%), or during a preoperative examination for an aesthetic surgery
      (20.5%) (P = 0.0082). CONCLUSIONS: The results suggest that implant ruptures of
      silicone gel breast implants are under diagnosed. Clinical follow-up seems
      insufficient to diagnose implant ruptures. Ultra sound surveillance (+/- MRI)
      could be proposed 4 years, 7 years and 10 years after the initial surgery. It
      does not seem appropriate to propose a systematic change of implant without the
      incidence of a rupture.

PMID- 26296965
TI  - Tracking Pavement Cells through Space and Time: Microtubules Define Positions of
      Lobe Formation.

PMID- 26296963
TI  - Nitrogen-Fixing Nodules Are an Important Source of Reduced Sulfur, Which Triggers
      Global Changes in Sulfur Metabolism in Lotus japonicus.
AB  - We combined transcriptomic and biochemical approaches to study rhizobial and
      plant sulfur (S) metabolism in nitrogen (N) fixing nodules (Fix(+)) of Lotus
      japonicus, as well as the link of S-metabolism to symbiotic nitrogen fixation and
      the effect of nodules on whole-plant S-partitioning and metabolism. Our data
      reveal that N-fixing nodules are thiol-rich organs. Their high adenosine 5'
      phosphosulfate reductase activity and strong (35)S-flux into cysteine and its
      metabolites, in combination with the transcriptional upregulation of several
      rhizobial and plant genes involved in S-assimilation, highlight the function of
      nodules as an important site of S-assimilation. The higher thiol content observed
      in nonsymbiotic organs of N-fixing plants in comparison to uninoculated plants
      could not be attributed to local biosynthesis, indicating that nodules are an
      important source of reduced S for the plant, which triggers whole-plant
      reprogramming of S-metabolism. Enhanced thiol biosynthesis in nodules and their
      impact on the whole-plant S-economy are dampened in plants nodulated by Fix(-)
      mutant rhizobia, which in most respects metabolically resemble uninoculated
      plants, indicating a strong interdependency between N-fixation and S
      assimilation. 

PMID- 26296964
TI  - The Axial Element Protein DESYNAPTIC2 Mediates Meiotic Double-Strand Break
      Formation and Synaptonemal Complex Assembly in Maize.
AB  - During meiosis, homologous chromosomes pair and recombine via repair of
      programmed DNA double-strand breaks (DSBs). DSBs are formed in the context of
      chromatin loops, which are anchored to the proteinaceous axial element (AE). The
      AE later serves as a framework to assemble the synaptonemal complex (SC) that
      provides a transient but tight connection between homologous chromosomes. Here,
      we showed that DESYNAPTIC2 (DSY2), a coiled-coil protein, mediates DSB formation
      and is directly involved in SC assembly in maize (Zea mays). The dsy2 mutant
      exhibits homologous pairing defects, leading to sterility. Analyses revealed that
      DSB formation and the number of RADIATION SENSITIVE51 (RAD51) foci are largely
      reduced, and synapsis is completely abolished in dsy2 meiocytes. Super-resolution
      structured illumination microscopy showed that DSY2 is located on the AE and
      forms a distinct alternating pattern with the HORMA-domain protein ASYNAPTIC1
      (ASY1). In the dsy2 mutant, localization of ASY1 is affected, and loading of the
      central element ZIPPER1 (ZYP1) is disrupted. Yeast two-hybrid and bimolecular
      fluorescence complementation experiments further demonstrated that ZYP1 interacts
      with DSY2 but does not interact with ASY1. Therefore, DSY2, an AE protein, not
      only mediates DSB formation but also bridges the AE and central element of SC
      during meiosis. 

PMID- 26296966
TI  - The RING-Finger Ubiquitin Ligase HAF1 Mediates Heading date 1 Degradation during
      Photoperiodic Flowering in Rice.
AB  - The photoperiodic response is one of the most important factors determining
      heading date in rice (Oryza sativa). Although rhythmic expression patterns of
      flowering time genes have been reported to fine-tune the photoperiodic response,
      posttranslational regulation of key flowering regulators has seldom been
      elucidated in rice. Heading date 1 (Hd1) encodes a zinc finger transcription
      factor that plays a crucial role in the photoperiodic response, which determines
      rice regional adaptability. However, little is known about the molecular
      mechanisms of Hd1 accumulation during the photoperiod response. Here, we identify
      a C3HC4 RING domain-containing E3 ubiquitin ligase, Heading date Associated
      Factor 1 (HAF1), which physically interacts with Hd1. HAF1 mediates
      ubiquitination and targets Hd1 for degradation via the 26S proteasome-dependent
      pathway. The haf1 mutant exhibits a later flowering heading date under both short
      day and long-day conditions. In addition, the haf1 hd1 double mutant headed as
      late as hd1 plants under short-day conditions but exhibited a heading date
      similar to haf1 under long-day conditions, thus indicating that HAF1 may
      determine heading date mainly through Hd1 under short-day conditions. Moreover,
      high levels of Hd1 accumulate in haf1. Our results suggest that HAF1 is essential
      to precise modulation of the timing of Hd1 accumulation during the photoperiod
      response in rice. 

PMID- 26296967
TI  - Differential Growth in Periclinal and Anticlinal Walls during Lobe Formation in
      Arabidopsis Cotyledon Pavement Cells.
AB  - Lobe development in the epidermal pavement cells of Arabidopsis thaliana
      cotyledons and leaves is thought to take place via tip-like growth on the concave
      side of lobes driven by localized concentrations of actin filaments and
      associated proteins, with a predicted role for cortical microtubules in
      establishing the direction of restricted growth at the convex side. We used
      homologous landmarks fixed to the outer walls of pavement cells and thin-plate
      spline analysis to demonstrate that lobes form by differential growth of both the
      anticlinal and periclinal walls. Most lobes formed within the first 24 h of the
      cotyledons unfurling, during the period of rapid cell expansion. Cortical
      microtubules adjacent to the periclinal wall were persistently enriched at the
      convex side of lobes during development where growth was anisotropic and were
      less concentrated or absent at the concave side where growth was promoted.
      Alternating microtubule-enriched and microtubule-free zones at the periclinal
      wall in neighboring cells predicted sites of new lobes. There was no particular
      arrangement of cortical actin filaments that could predict where lobes would
      form. However, drug studies demonstrate that both filamentous actin and
      microtubules are required for lobe formation. 

PMID- 26296968
TI  - Leukemia inhibitory factor protects cholangiocarcinoma cells from drug-induced
      apoptosis via a PI3K/AKT-dependent Mcl-1 activation.
AB  - Cholangiocarcinoma is an aggressive, strongly chemoresistant liver malignancy.
      Leukemia inhibitory factor (LIF), an IL-6 family cytokine, promotes progression
      of various carcinomas. To investigate the role of LIF in cholangiocarcinoma, we
      evaluated the expression of LIF and its receptor (LIFR) in human samples. LIF
      secretion and LIFR expression were assessed in established and primary human
      cholangiocarcinoma cell lines. In cholangiocarcinoma cells, we tested LIF effects
      on proliferation, invasion, stem cell-like phenotype, chemotherapy-induced
      apoptosis (gemcitabine+cisplatin), expression levels of pro-apoptotic (Bax) and
      anti-apoptotic (Mcl-1) proteins, with/without PI3K inhibition, and of pSTAT3,
      pERK1/2, pAKT. LIF effect on chemotherapy-induced apoptosis was evaluated after
      LIFR silencing and Mcl-1 inactivation.Results show that LIF and LIFR expression
      were higher in neoplastic than in control cholangiocytes; LIF was also expressed
      by tumor stromal cells. LIF had no effects on cholangiocarcinoma cell
      proliferation, invasion, and stemness signatures, whilst it counteracted drug
      induced apoptosis. Upon LIF stimulation, decreased apoptosis was associated with
      Mcl-1 and pAKT up-regulation and abolished by PI3K inhibition. LIFR silencing and
      Mcl-1 blockade restored drug-induced apoptosis.In conclusion, autocrine and
      paracrine LIF signaling promote chemoresistance in cholangiocarcinoma by up
      regulating Mcl-1 via a novel STAT3- and MAPK-independent, PI3K/AKT-dependent
      pathway. Targeting LIF signaling may increase CCA responsiveness to chemotherapy.

PMID- 26296969
TI  - Semi-synthetic ocotillol analogues as selective ABCB1-mediated drug resistance
      reversal agents.
AB  - Overexpression of ATP-Binding Cassette transporters leads to multidrug resistance
      in cancer cells and results in the failure of chemotherapy. In this in-vitro
      study, we investigated whether or not (20S, 24R/S)-epoxy-12beta, 25-dihydroxy
      dommarane-3beta-amine (ORA and OSA), a pair of semi-synthetic ocotillol analogue
      epimers, could inhibit the ABCB1 transporter. ORA (1 MUM and 3 MUM) significantly
      reversed the resistance to paclitaxel and vincristine in ABCB1-overexpressing
      SW620/Ad300 and HEK/ABCB1 cells, whereas OSA had no significant effects. In
      addition, ORA (3 MUM) significantly increased the intracellular accumulation of
      [3H]-paclitaxel by suppressing the efflux function of ABCB1. Meanwhile, both ORA
      (3 MUM) and OSA (3 MUM) did not significantly alter the expression level or the
      subcellular location of ABCB1 protein. Moreover, the ABCB1 ATPase study suggested
      that ORA had a stronger stimulatory effect on the ATPase activity than OSA. ORA
      also exhibited a higher docking score as compared with OSA inside transmembrane
      domain of ABCB1. Overall, we concluded that ORA reverse ABCB1-mediated MDR by
      competitively inhibiting the ABCB1 drug efflux function. 

PMID- 26296970
TI  - Detection of soluble EpCAM (sEpCAM) in malignant ascites predicts poor overall
      survival in patients treated with catumaxomab.
AB  - EpCAM is an attractive target for cancer therapy and the EpCAM-specific antibody
      catumaxomab has been used for intraperitoneal treatment of EpCAM-positive cancer
      patients with malignant ascites. New prognostic markers are necessary to select
      patients that mostly benefit from catumaxomab. Recent data showed that soluble
      EpCAM (sEpCAM) is capable to block the effect of catumaxomab in vitro. This
      exploratory retrospective analysis was performed on archived ascites samples to
      evaluate the predictive role of sEpCAM in catumaxomab-treated patients. Sixty-six
      catumaxomab-treated patients with an available archived ascites sample were
      included in this study and tested for sEpCAM by sandwich ELISA. All probes were
      sampled before treatment start and all patients received at least one catumaxomab
      infusion. Overall survival, puncture-free survival and time to next puncture were
      compared between sEpCAM-positive and -negative patients. We detected sEpCAM in
      ascites samples of 9 patients (13.6%). These patients showed a significantly
      shorter overall survival. The prognostic significance of sEpCAM in ascites was
      particularly strong in patients with ovarian cancer. Puncture-free survival and
      time to next puncture were not significantly different between sEpCAM-positive
      and -negative patients. We propose sEpCAM in malignant ascites as a potential
      predictive marker in cancer patients treated with catumaxomab. Prospective
      studies with larger patients samples are urgently needed to confirm these
      findings and studies testing dose-intensified catumaxomab in patients with sEpCAM
      positive ascites should be envisaged. 

PMID- 26296972
TI  - Plasma biomarkers of clinical response during chemotherapy plus combination
      antiretroviral therapy (cART) in HIV+ patients with advanced Kaposi sarcoma.
AB  - This study aimed to evaluate plasma concentration of selected cancer-associated
      inflammatory and immune-modulated cytokines in HIV+ patients with advanced Kaposi
      sarcoma (KS), and to explore candidate biomarkers capable of predicting clinical
      outcome in response to chemotherapy (CT) plus combination antiretroviral therapy
      (cART).Thirty-seven plasma cytokines/chemokines were assessed by Luminex
      technology in 27 consecutive HIV+ KS patients, followed-up during CT and cART of
      maintenance (m-cART). Associations between plasma concentration of biomarkers and
      patient clinical response to m-cART were evaluated by means of Hazard Ratios
      (HRs) and corresponding 95% Confidence Intervals (CIs).Plasma baseline
      concentration of Granulocyte colony-stimulating factor (G-CSF), Hepatocyte growth
      factor (HGF) and endoglin were found to be associated with m-cART clinical
      response (HR:1.56, 95%CI:1.09-2.22, p = 0.01; HR:0.32, 95% CI:0.10-0.99, p =
      0.05; HR:0.72, 95% CI:0.54-0.96, p = 0.03, respectively). The multivariate
      analysis confirmed the associations of baseline plasma G-CSF and HGF
      concentration with m-cART clinical complete remission response (HR:1.78, 95%
      CI:1.15-2.74, p = 0.009; HR:0.19, 95% CI:0.04-0.95, p = 0.04). Our exploratory
      study suggested that plasma G-CSF, HGF and endoglin may be novel predictors of
      clinical response during m-cART in HIV+ KS patients. Nonetheless, these findings
      should be further validated in an independent population study.

PMID- 26296971
TI  - miRNA-7/21/107 contribute to HBx-induced hepatocellular carcinoma progression
      through suppression of maspin.
AB  - Maspin suppresses tumor progression by promoting cell adhesion and apoptosis and
      by inhibiting cell motility. However, its role in tumorigenesis of hepatocellular
      carcinoma (HCC) remains unclear. The gene regulation of maspin and its
      relationship with HCC patient prognosis were investigated in this study. Maspin
      expression was specifically reduced in HBV-associated patients and correlated
      with their poor prognosis. Maspin downregulation in HCC cells was induced by HBx
      to promote their motility and resistance to anoikis and chemotherapy. HBx
      dependent induction of microRNA-7, -107, and -21 was further demonstrated to
      directly target maspin mRNA, leading to its protein downregulation. Higher
      expressions of these microRNAs also correlated with maspin downregulation in HBV
      associated patients, and were associated with their poor overall survival. These
      data not only provided new insights into the molecular mechanisms of maspin
      deficiency by HBx, but also indicated that downregulation of maspin by microRNAs
      confers HBx-mediated aggressiveness and chemoresistance in HCC. 

PMID- 26296973
TI  - Patient-derived cell models as preclinical tools for genome-directed targeted
      therapy.
AB  - BACKGROUND: In this study, we established patient-derived tumor cell (PDC) models
      using tissues collected from patients with metastatic cancer and assessed whether
      these models could be used as a tool for genome-based cancer treatment. METHODS:
      PDCs were isolated and cultured from malignant effusions including ascites and
      pleural fluid. Pathological examination, immunohistochemical analysis, and
      genomic profiling were performed to compare the histological and genomic features
      of primary tumors, PDCs. An exploratory gene expression profiling assay was
      performed to further characterize PDCs. RESULTS: From January 2012 to May 2013,
      176 samples from patients with metastatic cancer were collected. PDC models were
      successfully established in 130 (73.6%) samples. The median time from specimen
      collection to passage 1 (P1) was 3 weeks (range, 0.5-4 weeks), while that from P1
      to P2 was 2.5 weeks (range, 0.5-5 weeks). Sixteen paired samples of genomic
      alterations were highly concordant between each primary tumor and progeny PDCs,
      with an average variant allele frequency (VAF) correlation of 0.878. We compared
      genomic profiles of the primary tumor (P0), P1 cells, P2 cells, and patient
      derived xenografts (PDXs) derived from P2 cells and found that three samples (P0,
      P1, and P2 cells) were highly correlated (0.99-1.00). Moreover, PDXs showed more
      than 100 variants, with correlations of only 0.6-0.8 for the other samples. Drug
      responses of PDCs were reflective of the clinical response to targeted agents in
      selected patient PDC lines. CONCLUSION(S): Our results provided evidence that our
      PDC model was a promising model for preclinical experiments and closely resembled
      the patient tumor genome and clinical response.

PMID- 26296974
TI  - Protein kinase C-related kinase 1 and 2 play an essential role in thromboxane
      mediated neoplastic responses in prostate cancer.
AB  - The prostanoid thromboxane (TX) A2 is increasingly implicated in neoplastic
      progression, including prostate cancer (PCa). Mechanistically, we recently
      identified protein kinase C-related kinase (PRK) 1 as a functional interactant of
      both the TPalpha and TPbeta isoforms of the human T prostanoid receptor (TP). The
      interaction with PRK1 was not only essential for TPalpha/TPbeta-induced PCa cell
      migration but also enabled the TXA2-TP axis to induce phosphorylation of histone
      H3 at Thr11 (H3Thr11), an epigenetic marker both essential for and previously
      exclusively associated with androgen-induced chromatin remodelling and
      transcriptional activation. PRK1 is a member of a subfamily of three structurally
      related kinases comprising PRK1/PKNalpha, PRK2/PKNgamma and PRK3/PKNbeta that are
      widely yet differentially implicated in various cancers. Hence, focusing on the
      setting of prostate cancer, this study investigated whether TPalpha and/or TPbeta
      might also complex with PRK2 and PRK3 to regulate their activity and neoplastic
      responses. While TPalpha and TPbeta were found in immune complexes with PRK1,
      PRK2 and PRK3 to regulate their activation and signalling, they do so
      differentially and in a TP agonist-regulated manner dependent on the T-loop
      activation status of the PRKs but independent of their kinase activity.
      Furthermore, TXA2-mediated neoplastic responses in prostate adenocarcinoma PC-3
      cells, including histone H3Thr11 phosphorylation, was found to occur through a
      PRK1- and PRK2-, but not PRK3-, dependent mechanism. Collectively, these data
      suggest that TXA2 acts as both a neoplastic and epigenetic regulator and provides
      a mechanistic explanation, at least in part, for the prophylactic benefits of
      Aspirin in reducing the risk of certain cancers. 

PMID- 26296976
TI  - NK cells in asthma exacerbation.

PMID- 26296975
TI  - Zinc finger transcription factor CASZ1 interacts with histones, DNA repair
      proteins and recruits NuRD complex to regulate gene transcription.
AB  - The zinc finger transcription factor CASZ1 has been found to control neural fate
      determination in flies, regulate murine and frog cardiac development, control
      murine retinal cell progenitor expansion and function as a tumor suppressor gene
      in humans. However, the molecular mechanism by which CASZ1 regulates gene
      transcription to exert these diverse biological functions has not been described.
      Here we identify co-factors that are recruited by CASZ1b to regulate gene
      transcription using co-immunoprecipitation (co-IP) and mass spectrometry assays.
      We find that CASZ1b binds to the nucleosome remodeling and histone deacetylase
      (NuRD) complex, histones and DNA repair proteins. Mutagenesis of the CASZ1b
      protein assay demonstrates that the N-terminus of CASZ1b is required for NuRD
      binding, and a poly(ADP-ribose) binding motif in the CASZ1b protein is required
      for histone H3 and DNA repair proteins binding. The N-terminus of CASZ1b fused to
      an artificial DNA-binding domain (GAL4DBD) causes a significant repression of
      transcription (5xUAS-luciferase assay), which could be blocked by treatment with
      an HDAC inhibitor. Realtime PCR results show that the transcriptional activity of
      CASZ1b mutants that abrogate NuRD or histone H3/DNA binding is significantly
      decreased. This indicates a model in which CASZ1b binds to chromatin and recruits
      NuRD complexes to orchestrate epigenetic-mediated transcriptional programs. 

PMID- 26296977
TI  - IL-37 restrains autoimmune diseases.

PMID- 26296978
TI  - Hedgehog fuels gut regeneration.

PMID- 26296979
TI  - Positive feedback loop of hepatoma-derived growth factor and beta-catenin
      promotes carcinogenesis of colorectal cancer.
AB  - To clarify the role of hepatoma-derived growth factor (HDGF) and beta-catenin in
      carcinogenesis of colorectal cancer (CRC), our results showed that high HDGF
      expression was found in CRC cells and tissues and significantly related to
      histological differentiation (p = 0.035) and lymph node metastasis (p = 0.000).
      Significant positive correlation between HDGF expression and beta-catenin
      abnormal expression was found in CRC tissues. High HDGF and lymph node metastasis
      were the strong independent prognostic indicators for reduced overall survival in
      CRC patients. HDGF knockdown dramatically inhibited cellular proliferation,
      migration, invasion, and tumorigenesis, both in vitro and in vivo, but induced G1
      phase arrest and apoptosis in CRC cells. HDGF knock-down dramatically suppressed
      beta-catenin and its down-stream genes expression in CRC cells. Intriguingly,
      beta-catenin knock-down dramatically suppressed HDGF expression in CRC cells.
      Human recombinant Wnt3a and DKK1 treatment increased and decreased HDGF, beta
      catenin, c-Myc, cyclin D1, MMP9, and phos-GSK-3beta (Ser9) protein expression in
      nuclear and cytoplasmic fraction of CRC cells upon beta-catenin knock-down,
      respectively. Three HDGF-binding elements in beta-catenin promoter were found and
      specific for transcriptional activation of beta-catenin in CRC cells. In
      conclusion, our results first suggest that HDGF and beta-catenin interacts as a
      positive feedback loop, which plays an important role in carcinogenesis and
      progression of CRC. 

PMID- 26296981
TI  - [Effect of low dose dexmedetomidine premedication on propofol consumption in
      geriatric end stage renal disease patients].
AB  - BACKGROUND AND OBJECTIVE: Sedation in dialysis dependent end-stage renal disease
      patients requires caution as a result of performing high doses of sedatives and
      its complications. Multidrug sedation regimens might be superior and advantage on
      lesser drug consumption and by the way adverse events which occur easily in end
      stage renal disease patients. We evaluated the effects of dexmedetomidine
      premedication on propofol consumption, sedation levels with Observer's Assessment
      of Alertness and Sedation scores and the bispectral index and the hemodynamic
      changes, potential side effects in geriatric patients with end-stage renal
      disease who underwent hip fracture surgery under spinal anesthesia. METHOD: In
      this randomized, controlled, double-blind study 60 elderly patients (age>=65
      years) with end-stage renal disease and hip fracture scheduled for anterograde
      femoral intramedullary nailing were assigned to groups that received either
      intravenous saline infusion (Group C) or dexmedetomidine 0.5MUg/kg/10min infusion
      for premedication (Group D). All the patients received propofol infusion after
      the induction of the spinal anesthesia. RESULTS: Total propofol consumption,
      propofol dose required for targeted sedation levels according to Observer's
      Assessment of Alertness and Sedation scores and bispectral index levels, recovery
      times were significantly lower in Group D (p<0.001). The time to reach to
      Observer's Assessment of Alertness and Sedation score 4 and to achieve bispectral
      index<=80 was significantly lower in Group C compared with Group D (p<0.001).
      Adverse events were similar in both groups. CONCLUSION: Dexmedetomidine
      premedication lowers intraoperative propofol consumption to maintain targeted
      level of sedation. Therefore low dose dexmedetomidine premedication in addition
      to propofol infusion might be an alternative in geriatric patients with end-stage
      renal disease for sedation.

PMID- 26296982
TI  - [Current concepts on hemodynamic support and therapy in septic shock].
AB  - Severe sepsis and septic shock represent a major healthcare challenge. Much of
      the improvement in mortality associated with septic shock is related to early
      recognition combined with timely fluid resuscitation and adequate antibiotics
      administration. The main goals of septic shock resuscitation include
      intravascular replenishment, maintenance of adequate perfusion pressure and
      oxygen delivery to tissues. To achieve those goals, fluid responsiveness
      evaluation and complementary interventions - i.e. vasopressors, inotropes and
      blood transfusion - may be necessary. This article is a literature review of the
      available evidence on the initial hemodynamic support of the septic shock
      patients presenting to the emergency room or to the intensive care unit and the
      main interventions available to reach those targets, focusing on fluid and
      vasopressor therapy, blood transfusion and inotrope administration. 

PMID- 26296983
TI  - [The influence of airway supporting maneuvers on glottis view in pediatric
      fiberoptic bronchoscopy].
AB  - INTRODUCTION: Flexible fiber optic bronchoscopy is a valuable intervention for
      evaluation and management of respiratory diseases in both infants, pediatric and
      adult patients. The aim of this study is to investigate the influence of the
      airway supporting maneuvers on glottis view during pediatric flexible fiberoptic
      bronchoscopy. MATERIALS AND METHODS: In this randomized, controlled, crossover
      study; patients aged between 0 and 15 years who underwent flexible fiberoptic
      bronchoscopy procedure having American Society of Anesthesiologists I-II risk
      score were included. Patients having risk of difficult intubation, intubated or
      patients with tracheostomy, and patients with reduced neck mobility or having
      cautions for neck mobility were excluded from this study. After obtaining best
      glottic view at the neutral position, patients were positioned jaw trust with
      open mouth, jaw trust with teeth prottution, head tilt chin lift and triple
      airway maneuvers and best glottis scores were recorded. RESULTS: Total of 121
      pediatric patients, 57 girls and 64 boys, were included in this study. Both jaw
      trust with open mouth and jaw trust with teeth prottution maneuvers improved the
      glottis view compared with neutral position (p<0.05), but we did not observe any
      difference between jaw trust with open mouth and jaw trust with teeth prottution
      maneuvers (p>0.05). Head tilt chin lift and triple airway maneuvers improved
      glottis view when compared with both jaw trust with open mouth and jaw trust with
      teeth prottution maneuvers and neutral position (p<0.05); however we found no
      differences between head tilt chin lift and triple airway maneuvers (p>0.05).
      CONCLUSION: All airway supporting maneuvers improved glottic view during
      pediatric flexible fiberoptic bronchoscopy; however head tilt chin lift and
      triple airway maneuvers were found to be the most effective maneuvers.

PMID- 26296984
TI  - Bleeding Associated With Feeding Tube Placement in Critically Ill Oncology
      Patients With Thrombocytopenia.
AB  - BACKGROUND: Existing trials have not evaluated the feasibility of oral or nasal
      feeding tube (FT) placement in the critically ill thrombocytopenic oncology
      population. Thrombocytopenia (TCP) may be considered a contraindication to FT
      placement due to the potential risk of bleeding complications. METHODS: Medical
      intensive care unit (ICU) adult oncology patients with attempted nasal or oral FT
      placement were evaluated in a 52-bed ICU at a comprehensive cancer center. End
      points were compared between patients with and without TCP (platelet count
      <150,000/MUL). Primary outcomes of overt and clinically important bleeding
      (gastrointestinal and point of entry) were evaluated within 72 hours of FT
      placement. RESULTS: Fifty-nine patients were enrolled (TCP, n = 42; no TCP, n =
      17; baseline platelet count, 41 +/- 48 vs 249 +/- 85 [* 10(3)/MUL], P < .001).
      Patients with TCP were more likely to have a hematologic malignancy and lower
      baseline hemoglobin and platelet count (P < .01). More patients with TCP received
      blood products 24 hours prior to FT placement (86% vs 12%, P < .01). There was no
      difference in overt (7.1% vs 0%, P = .55) or clinically important (2.4% vs 5.9%,
      P = .5) bleeding complications within 72 hours of attempted FT placement among
      patients with TCP versus those without. CONCLUSIONS: Critically ill oncology
      patients with TCP do not appear to be at a higher risk for bleeding complications
      after FT placement compared with those without TCP, which may be related to blood
      product transfusion within 24 hours prior to FT placement.

PMID- 26296985
TI  - Ultrasound-Propelled Nanocups for Drug Delivery.
AB  - Ultrasound-induced bubble activity (cavitation) has been recently shown to
      actively transport and improve the distribution of therapeutic agents in tumors.
      However, existing cavitation-promoting agents are micron-sized and cannot sustain
      cavitation activity over prolonged time periods because they are rapidly
      destroyed upon ultrasound exposure. A novel ultrasound-responsive single-cavity
      polymeric nanoparticle (nanocup) capable of trapping and stabilizing gas against
      dissolution in the bloodstream is reported. Upon ultrasound exposure at
      frequencies and intensities achievable with existing diagnostic and therapeutic
      systems, nanocups initiate and sustain readily detectable cavitation activity for
      at least four times longer than existing microbubble constructs in an in vivo
      tumor model. As a proof-of-concept of their ability to enhance the delivery of
      unmodified therapeutics, intravenously injected nanocups are also found to
      improve the distribution of a freely circulating IgG mouse antibody when the
      tumor is exposed to ultrasound. Quantification of the delivery distance and
      concentration of both the nanocups and coadministered model therapeutic in an in
      vitro flow phantom shows that the ultrasound-propelled nanocups travel further
      than the model therapeutic, which is itself delivered to hundreds of microns from
      the vessel wall. Thus nanocups offer considerable potential for enhanced drug
      delivery and treatment monitoring in oncological and other biomedical
      applications. 

PMID- 26296986
TI  - Right ventricular remodeling, its correlates, and its clinical impact in
      hypertrophic cardiomyopathy.
AB  - BACKGROUND: Structural right ventricular (RV) abnormalities are present in a
      substantial proportion of patients with hypertrophic cardiomyopathy (HCM), but
      the trigger for RV hypertrophy remains unclear. The aim of this study was to
      assess the relationship between RV and left ventricular (LV) remodeling and the
      impact of biventricular involvement on clinical status in this setting. METHODS:
      Ninety-nine patients with HCM and 30 normal subjects with a similar age and
      gender distribution were prospectively enrolled. Comprehensive echocardiography
      was performed in all, including the assessment of LV and RV function by tissue
      Doppler and speckle-tracking echocardiography. Measurement of RV free wall
      thickness (RVWT) was performed at end-diastole, in a zoomed subcostal view,
      focusing on the RV midwall. RESULTS: Patients with HCM had increased RVWT (6.4 +/
      1.9 vs 3.6 +/- 0.8 mm, P < .001) and lower values of RV global longitudinal
      strain (-19.4 +/- 4.4% vs -23.8 +/- 2.7%, P < .001) compared with control
      subjects. RVWT was independently related to LV mass and LV global longitudinal
      strain. Increased RVWT was correlated with New York Heart Association class (r =
      0.20, P = .04) and calculated sudden cardiac death risk score (r = 0.52, P <
      .001) and was independently related to the presence of ventricular arrhythmias
      (odds ratio, 2.02; 95% CI, 1.28-3.19; P = .002). CONCLUSIONS: In patients with
      HCM, the presence of RV hypertrophy was associated with increased LV mass and
      reduced LV longitudinal strain, correlated with increased calculated sudden
      cardiac death risk score, and independently related to the presence of
      ventricular arrhythmias. These data suggest more severe disease in patients with
      biventricular HCM.

PMID- 26296987
TI  - Capillary electrophoresis study on segment/segment system for segments based on
      phase of mixed micelles and its role in transport of particles between the two
      segments.
AB  - Capillary electrophoresis coupled with contactless conductivity detector was
      applied to characterize BGE/segment/segment/BGE and
      BGE/segment/electrolyte/segment/BGE systems, where segment is the phase of mixed
      micelles migrating surrounded by BGE and composition of the first segment?second
      segment. It was established that both systems are subject of evolution during
      electrophoretic run induced by different electrophoretic mobilities of segments
      and the phenomenon that generates the evolution is exchange of micelles between
      the two segments. This leads to segments re-equilibration during a run, which
      generates sub-zones from the two segments in the form of a cumulative zone or two
      isolated zones, depending on the injection scheme applied. Further analysis based
      on the system BGE/segment/electrolyte/segment/BGE shows that electrolyte solution
      between segments can act as a spacer to isolate the two micellar segments, and
      thereby to control the exchange of micelles between the two segments. Established
      features for both systems were further implemented towards characterization of
      the transport of nanocrystals (NCs) between two segments using CE/UV-vis
      technique and two examples were discussed: (i) on-line coating of NCs with
      surfactants and (ii) distribution of NCs between segments. The former aspect was
      found to be useful to discuss the state of particle in micellar media, whereas
      the latter shows system ability for the transport of NCs from the first segment
      or BGE based sample to the second segment, controlled by the electrolyte
      characteristics. It was concluded that transport of micelles and NCs is the
      subject of the same phenomena since basic electrolyte characteristics, i.e.
      length and concentration, act in the same way. This means that NCs in these
      systems can play the role of pseudomicelles, which mimic behaviour of micelles.
      Definitely, the tools established in the present work can be used to examine
      dynamic phenomena for pseudophase during electrophoresis and for NCs migrating in
      the presence of pseudophase in various configurations. 

PMID- 26296988
TI  - Anionic metabolite profiling by capillary electrophoresis-mass spectrometry using
      a noncovalent polymeric coating. Orange juice and wine as case studies.
AB  - In several metabolomic studies, it has already been demonstrated that capillary
      electrophoresis hyphenated to mass spectrometry (CE-MS) can detect an important
      group of highly polar and ionized metabolites that are overseen by techniques
      such as NMR, LC-MS and GC-MS, providing complementary information. In this work,
      we present a strategy for anionic metabolite profiling by CE-MS using a cationic
      capillary coating. The polymer, abbreviated as PTH, is composed of a poly
      (N,N,N',N'-tetraethyldiethylenetriamine, N-(2-hydroxypropyl) methacrylamide,
      TEDETAMA-co-HPMA (50:50) copolymer. A CE-MS method based on PTH-coating was
      optimized for the analysis of a group of 16 standard anionic metabolites.
      Separation was achieved within 12min, with high separation efficiency (up to
      92,000 theoretical plates per meter), and good repeatability, namely, relative
      standard deviation values for migration times and peak areas were below 0.2 and
      2.1%, respectively. The optimized method allowed the detection of 87 metabolites
      in orange juice and 142 metabolites in red wine, demonstrating the good
      possibilities of this strategy for metabolomic applications. 

PMID- 26296989
TI  - Identifying potential exposure reduction priorities using regional rankings based
      on emissions of known and suspected carcinogens to outdoor air in Canada.
AB  - BACKGROUND: Emissions inventories aid in understanding the sources of hazardous
      air pollutants and how these vary regionally, supporting targeted reduction
      actions. Integrating information on the relative toxicity of emitted pollutants
      with respect to cancer in humans helps to further refine reduction actions or
      recommendations, but few national programs exist in North America that use
      emissions estimates in this way. The CAREX Canada Emissions Mapping Project
      provides key regional indicators of emissions (total annual and total annual
      toxic equivalent, circa 2011) of 21 selected known and suspected carcinogens.
      METHODS: The indicators were calculated from industrial emissions reported to the
      National Pollutant Release Inventory (NPRI) and estimates of emissions from
      transportation (airports, trains, and car and truck traffic) and residential
      heating (oil, gas and wood), in conjunction with human toxicity potential
      factors. We also include substance-specific annual emissions in toxic equivalent
      kilograms and annual emissions in kilograms, to allow for ranking substances
      within any region. RESULTS: For provinces and territories in Canada, the
      indicators suggest the top five substances contributing to the total toxic
      equivalent emissions in any region could be prioritized for further
      investigation. Residents of Quebec and New Brunswick may be more at risk of
      exposure to industrial emissions than those in other regions, suggesting that a
      more detailed study of exposure to industrial emissions in these provinces is
      warranted. Residential wood smoke may be an important emission to control,
      particularly in the north and eastern regions of Canada. Residential oil and gas
      heating, along with rail emissions contribute little to regional emissions and
      therefore may not be an immediate regional priority. CONCLUSIONS: The developed
      indicators support the identification of pollutants and sources for additional
      investigation when planning exposure reduction actions among Canadian provinces
      and territories, but have important limitations similar to other emissions
      inventory-based tools. Additional research is required to evaluate how the
      Emissions Mapping Project is used by different groups and organizations with
      respect to informing actions aimed at reducing Canadians' potential exposure to
      harmful air pollutants.

PMID- 26296990
TI  - Translating stem cell research to the clinic: a primer on translational
      considerations for your first stem cell protocol.
AB  - Over the last two decades, a new therapeutic paradigm has emerged which has
      changed the way debilitating diseases may be treated in the future. Instead of
      using small-molecule drugs and devices to ameliorate the symptoms of disease,
      clinicians may harness the therapeutic power of cells to regenerate and cure
      diseases which currently represent a major unmet medical need. Advancements in
      the scientific knowledge of stem cell biology, along with highly encouraging
      preclinical proof-of-concept studies, in the last several years have served as a
      launch pad for testing such therapeutics in humans with life-threatening
      diseases. However, translating basic research findings into human therapy has not
      been straightforward and has presented many scientific, clinical, and regulatory
      challenges for scientists and clinicians. In this article, we provide a guidance
      framework for investigators for the design of early-phase clinical studies using
      stem cell-based therapeutics. Furthermore, important trial parameters and design
      features which must be considered before regulatory submission of such studies
      are highlighted. 

PMID- 26296991
TI  - A case series study of the neurophysiological effects of altered states of mind
      during intense Islamic prayer.
AB  - This paper presents a case series with preliminary data regarding the
      neurophysiological effects of specific prayer practices associated with the
      Islamic religion. Such practices, like other prayer practices, are likely
      associated with several coordinated cognitive activities and a complex pattern of
      brain physiology. However, there may also be changes specific to the goals of
      Islamic prayer which has, as its most fundamental concept, the surrendering of
      one's self to God. To evaluate Islamic prayer practices, we measured changes in
      cerebral blood flow (CBF) using single photon emission computed tomography
      (SPECT) in three Islamic individuals while practicing two different types of
      Islamic prayer. In this case series, intense Islamic prayer practices generally
      showed decreased CBF in the prefrontal cortex and related frontal lobe
      structures, and the parietal lobes. However, there were also several regions that
      differed between the two types of prayer practices including increased CBF in the
      caudate nucleus, insula, thalamus, and globus pallidus. These patterns also
      appear distinct from concentrative techniques in which an individual focuses on a
      particular idea or object. It is hypothesized that the changes in brain activity
      may be associated with feelings of "surrender" and "connectedness with God"
      described to be experienced during these intense Islamic prayer practices.
      Overall, these results suggest that several coordinated cognitive processes occur
      during intense Islamic prayer. Methodological issues and implications of the
      results are also discussed.

PMID- 26296992
TI  - Cytotoxicity of atropine to human corneal epithelial cells by inducing cell cycle
      arrest and mitochondrion-dependent apoptosis.
AB  - Atropine is an anticholinergic drug for mydriasis in eye clinic, and its abuse
      might be cytotoxic to the cornea and result in blurred vision. However, the
      cytotoxicity of atropine to the cornea and its cellular and molecular mechanisms
      remain unknown. In this study, we investigated the cytotoxicity of atropine to
      corneal epithelium and its underlying mechanisms using an in vitro model of non
      transfected human corneal epithelial (HCEP) cells. Our results showed that
      atropine, above the concentration of 0.3125 g/l (1/32 of its therapeutic dosage
      in eye clinic), had a dose- and time-dependent toxicity to HCEP cells by inducing
      morphological abnormality, cytopathic effect, viability decline, and
      proliferation retardation. Moreover, the proliferation-retarding effect of
      atropine on the cells was achieved by inducing G1/S phase arrest and
      downregulation of E-cadherin and beta-catenin. Besides, atropine also had an
      apoptosis-inducing effect on the cells by inducing phosphatidylserine
      externalization, plasma membrane permeability elevation, DNA fragmentation and
      apoptotic body formation. Furthermore, atropine could also induce activations of
      caspase-2, -3 and -9, disruption of mitochondrial transmembrane potential,
      downregulation of Bcl-2 and Bcl-xL, upregulation of Bax and Bad, and upregulation
      of cytoplasmic cytochrome c and apoptosis-inducing factor, implying a death
      receptor-mediated mitochondrion-dependent pathway is most probably involved in
      the apoptosis of HCEP cells induced by atropine. Taken together, our results
      suggest that atropine has remarkable cytotoxicity to HCEP cells by inducing cell
      cycle arrest and death receptor-mediated mitochondrion-dependent apoptosis.

PMID- 26296993
TI  - Primary open angle glaucoma in northern Nigeria: stage at presentation and
      acceptance of treatment.
AB  - BACKGROUND: To determine the stage of primary open angle glaucoma at presentation
      at a tertiary eye unit, to assess patient's knowledge of glaucoma and acceptance
      and subsequent adherence to treatment. METHOD: Information collected
      prospectively on new glaucoma patients aged 30 or more years included distance
      from residence and what they knew about glaucoma and its treatment. Treatment
      offered took account of disease severity and socioeconomic factors. Reasons for
      not accepting surgery were recorded. At follow up intraocular pressure (IOP) was
      measured and adherence to medication assessed verbally. Four categories of
      severity were defined based on visual acuity and visual fields defects in the
      worse eye. RESULTS: 131 patients were recruited (mean age 52.8 years; 62% male).
      Most attended because of symptoms (70%). Mean IOP in affected eyes was 31.9+/-SD
      12.4 and mean vertical cup:disc ratio was 0.8. 99 eyes (47%) had a visual acuity
      of light perception or worse. Risk factors for advanced/end-stage disease were
      age >50 years, living >10 km from the hospital, some awareness of glaucoma, not
      being literate, being unemployed and presenting with symptoms. In multivariable
      analysis older age and poor knowledge of glaucoma remained independent risk
      factors. 75 were offered trabeculectomy: five agreed but only one underwent
      surgery. Reasons for rejecting surgery were fear (37%), preferred medical
      treatment (27 %) and cost (15 %). 32/85 (24 %) participants started on topical
      medication attended follow up. 72% reported excellent compliance but only 56% of
      glaucomatous eyes had IOPs less than 21 mmHg. CONCLUSIONS: To prevent glaucoma
      blindness strategies are required which promote earlier detection, with
      counselling to promote acceptance of and adherence to treatment.

PMID- 26296995
TI  - Fusibacter fontis sp. nov., a sulfur-reducing, anaerobic bacterium isolated from
      a mesothermic Tunisian spring.
AB  - Strain KhalAKB1T, a mesophilic, anaerobic, rod-shaped bacterium, was isolated
      from water collected from a mesothermic Tunisian spring. Cells were Gram-staining
      positive rods, occurring singly or in pairs and motile by one lateral flagellum.
      Strain KhalAKB1T grew at 15-45  degrees C (optimum 30  degrees C), at pH 5.5-8.5
      (optimum pH 7.0) and in the presence of 0-35 g NaCl l- 1 (optimum 1 g NaCl l- 1).
      It fermented yeast extract and a wide range of carbohydrates including
      cellobiose, d-glucose, d-ribose, sucrose, d-xylose, maltose, d-galactose and
      starch as electron donors. Acetate, ethanol, CO2 and H2 were end products of
      glucose metabolism. It reduced elemental sulfur, but not sulfate, thiosulfate or
      sulfite, into sulfide. The DNA G+C content was 37.6 mol%. The predominant
      cellular fatty acids were C14 : 0 and C16 : 0. Phylogenetic analysis of the 16S
      rRNA gene sequence suggested Fusibacter bizertensis as the closest relative of
      this isolate (identity of 97.2 % to the type strain). Based on phenotypic,
      phylogenetic and genotypic taxonomic characteristics, strain KhalAKB1T is
      proposed to be assigned to a novel species within the genus Fusibacter, order
      Clostridiales, Fusibacter fontis sp. nov. The type strain is KhalAKB1T ( = DSM
      28450T = JCM 19912T). 

PMID- 26296994
TI  - Basic ICT adoption and use by general practitioners: an analysis of primary care
      systems in 31 European countries.
AB  - BACKGROUND: There is general consensus that appropriate development and use of
      information and communication technologies (ICT) are crucial in the delivery of
      effective primary care (PC). Several countries are defining policies to support
      and promote a structural change of the health care system through the
      introduction of ICT. This study analyses the state of development of basic ICT in
      PC systems of 31 European countries with the aim to describe the extent of, and
      main purposes for, computer use by General Practitioners (GPs) across Europe.
      Additionally, trends over time have been analysed. METHODS: Descriptive
      statistical analysis was performed on data from the QUALICOPC (Quality and Costs
      of Primary Care in Europe) survey, to describe the geographic differences in the
      general use of computer, and in specific computerized clinical functions for
      different health-related purposes such as prescribing, medication checking,
      generating health records and research for medical information on the Internet.
      RESULTS: While all the countries have achieved a near-universal adoption of a
      computer in their primary care practices, with only a few countries near or under
      the boundary of 90 %, the computerisation of primary care clinical functions
      presents a wide variability of adoption within and among countries and, in
      several cases (such as in the southern and central-eastern Europe), a large room
      for improvement. CONCLUSIONS: At European level, more efforts could be done to
      support southern and central-eastern Europe in closing the gap in adoption and
      use of ICT in PC. In particular, more attention seems to be need on the current
      usages of the computer in PC, by focusing policies and actions on the improvement
      of the appropriate usages that can impact on quality and costs of PC and can
      facilitate an interconnected health care system. However, policies and
      investments seem necessary but not sufficient to achieve these goals.
      Organizational, behavioural and also networking aspects should be taken in
      consideration.

PMID- 26296996
TI  - Changes in the hemolytic activity of Candida species by common electrolytes.
AB  - BACKGROUND: Hemolysins are crucial virulence factors which help pathogens to
      survive and persist in the host. This study investigated whether common
      electrolytes will affect the hemolysins of Candida species. The hemolysins from
      25 Candida isolates were investigated using a plate specially designed for
      Candida species in the presence of three electrolytes, CaCl2, NaCl and KCl, at
      different concentrations. The hemolytic activity was determined after 48 h and
      the hemolytic index was calculated. RESULTS: All three electrolytes caused a
      decrease in the hemolytic activity. Significant differences existed between
      varying concentrations of NaCl, while no significant differences existed for the
      CaCl2 and KCl groups. Additionally, the peripheral hemolytic index was highly
      correlated with the hemolytic index (r = 0.656, p < 0.001). CONCLUSIONS: Our
      findings indicate that electrolytes reduce hemolysis by Candida species and a
      correlation exists between the peripheral hemolytic index and the translucent
      hemolytic index.

PMID- 26296997
TI  - The topology of pen-2, a gamma-secretase subunit, revisited: evidence for a
      reentrant loop and a single pass transmembrane domain.
AB  - BACKGROUND: The gamma-secretase complex, composed of transmembrane proteins
      termed presenilin (PS), anterior pharynx defective (APH), nicastrin (NCT), and
      presenilin enhancer-2 (Pen-2) catalyzes intramembranous hydrolysis of a variety
      of Type I membrane protein substrates. In order to understand aspects of subunit
      assembly, interactions, dynamics and catalysis, it is essential to clarify the
      membrane topology of each polypeptide. Hydophathicity plots predict that the 101
      amino acid Pen-2 molecule has two hydrophobic domains (HP1 and HP2) that may
      serve as transmembrane spanning domains. Earlier reports indicated that
      transiently overexpressed Pen-2 uses these two hydrophobic domains as
      transmembrane helices that generates a "U-shaped" hairpin topology with both
      amino- (N-) and carboxyl-(C-) termini facing the lumen. In this report, we have
      reexamined the topology of endogenous Pen-2 and Pen-2 chimeras that are stably
      expressed in mammalian cells, and have assessed the function of these molecules
      in rescuing gamma-secretase activity in Pen-2-deficient fibroblasts. RESULTS: We
      confirm that the Pen-2 C-terminus is lumenal, but the N-terminus of Pen-2 is
      exposed to the cytoplasm, thus indicating that HP1 does not traverse the lipid
      bilayer as a transmembrane domain. Domain swapping studies reveal the importance
      of specific regions within the first hydrophobic domain of Pen-2 that are
      critical for generating the topology that is a prerequisite for mediating PS1
      endoproteolysis and gamma-secretase activity. Finally, we report that the first
      fourteen amino acids of the Pen-2 HP1 are required for gamma-secretase activity.
      CONCLUSIONS: We propose that the first hydrophobic domain of Pen-2 forms a
      structure similar to a reentrant loop while the second hydrophobic domain spans
      the lipid bilayer.

PMID- 26296998
TI  - Fabibacter misakiensis sp. nov., a marine bacterium isolated from coastal surface
      water.
AB  - A slightly curved-rod-shaped, pink-pigmented, Gram-stain-negative, aerobic
      bacterial strain with gliding motility, designated SK-8T, was isolated from
      coastal surface water of Misaki, Japan. Phylogenetic trees generated using 16S
      rRNA gene sequences revealed that strain SK-8T belonged to the genus Fabibacter
      and showed 96.0 % sequence similarity to the type strain of the most closely
      related species, Fabibacter pacificus DY53T. The novel isolate was phenotypically
      and physiologically different from previously described strains. The major
      cellular fatty acids were iso-C15 : 1 G, iso-C15 : 0 and iso-C17 : 0 3-OH. Major
      polar lipids were phosphatidylethanolamine, two aminophospholipids and an
      unidentified phospholipid. The DNA G+C content was 39.1 mol% and MK-7 was the
      only predominant isoprenoid quinone. On the basis of this taxonomic study
      employing a polyphasic approach, it was suggested that strain SK-8T represents a
      novel species of the genus Fabibacter, with the newly proposed name Fabibacter
      misakiensis sp. nov. The type strain is SK-8T ( = NBRC 110216T = KCTC 32969T).

PMID- 26296999
TI  - Comparison of two types of matrix-assisted laser desorption/ionization time-of
      flight mass spectrometer for the identification and typing of Clostridium
      difficile.
AB  - Microflex LT (Bruker Daltonics) and VITEK MS (bioMerieux) are bacterial
      identification systems that are based on matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). For VITEK
      MS, two identification softwares, VITEK MS IVD (IVD) and SARAMIS (SARAMIS), are
      available. Microflex LT is equipped with MALDI Biotyper RTC software (Biotyper).
      Although the identification accuracy of each instrument has been compared for
      various bacteria, no detailed examination has been conducted for the
      identification accuracy of Clostridium difficile. In this report, we compared the
      three identification softwares for identification reproducibility in three ATCC
      C. difficile strains and identification accuracy in 50 clinical C. difficile
      isolates. The results showed 100, 91.7 and 100 % identification reproducibility
      accuracy of ATCC strains when examined by IVD, SARAMIS and Biotyper software,
      respectively. For the identification of the clinical isolates, all three
      softwares exhibited satisfactory identification accuracy of C. difficile. Among
      the 50 clinical isolates, seven showed identical toxin genotype corresponding to
      the exact ribotype. However, MALDI-TOF MS failed to identify them as the
      identical type. Based on the above results, we concluded that both types of MALDI
      TOF MS reproducibly identified C. difficile; however, they are currently not
      suitable for typing of C. difficile clones. 

PMID- 26297000
TI  - Identification serologically, chemically and genetically of two Escherichia coli
      strains as candidates for new O serogroups.
AB  - Escherichia coli strains are normally identified by the combination of their O
      and H (and sometimes K) antigens, and serotyping based on the antigens is
      believed to be crucial for clinical detection and epidemiological investigation.
      Two E. coli strains, G5413 and G5287, were isolated from faecal samples of female
      patients with diarrhoea and were not agglutinated with any antisera that cover
      the well-known O serogroups of E. coli. We elucidated the O-polysaccharide (OPS)
      structures and analysed the O-antigen gene clusters of these bacteria. The OPS
      structure of G5413 established by monosaccharide analysis and NMR spectroscopy
      was found to be unique amongst known bacterial polysaccharide structures. The O
      antigen gene cluster of this strain was sequenced and did not match sequence data
      with any of the 184 O serogroups that have been recognized internationally. Gene
      functions were tentatively assigned and were appropriate to the OPS structure.
      Based on these data, we suggest G5413 as a candidate for a new E. coli O
      serogroup. Both the OPS structure and O-antigen gene cluster of G5287 were
      identical to those of E. coli L-19, a candidate for another new O serogroup
      characterized by us recently. Recognition of these two provisional O serogroups
      increases the number of known O-antigen forms of E. coli to 186. 

PMID- 26297001
TI  - Sialic acid-dependent interactions between influenza viruses and Streptococcus
      suis affect the infection of porcine tracheal cells.
AB  - Bacterial co-infections are a major complication in influenza-virus-induced
      disease in both humans and animals. Either of the pathogens may induce a host
      response that affects the infection by the other pathogen. A unique feature in
      the co-infection by swine influenza viruses (SIV) and Streptococcus suis serotype
      2 is the direct interaction between the two pathogens. It is mediated by the
      haemagglutinin of SIV that recognizes the alpha2,6-linked sialic acid present in
      the capsular polysaccharide of Streptococcus suis. In the present study, this
      interaction was demonstrated for SIV of both H1N1 and H3N2 subtypes as well as
      for human influenza viruses that recognize alpha2,6-linked sialic acid. Binding
      of SIV to Streptococcus suis resulted in co-sedimentation of virus with bacteria
      during low-speed centrifugation. Viruses bound to bacteria retained infectivity
      but induced only tiny plaques compared with control virus. Infection of porcine
      tracheal cells by SIV facilitated adherence of Streptococcus suis, which was
      evident by co-staining of bacterial and viral antigen. Sialic-acid-dependent
      binding of Streptococcus suis was already detectable after incubation for 30 min.
      By contrast, bacterial co-infection had a negative effect on the replication of
      SIV as indicated by lower virus titres in the supernatant and a delay in the
      kinetics of virus release. 

PMID- 26297002
TI  - Rapid detection of Mycobacterium tuberculosis complex by real-time PCR in sputum
      samples and its use in the routine diagnosis in a reference laboratory.
AB  - Tuberculosis (TB) is an infectious disease of global distribution, constituting a
      serious public health problem in Brazil. Sao Paulo State, located in the south
      east of Brazil, notified 16,580 new TB cases in 2013. The Instituto Adolfo Lutz
      is a public health reference laboratory for TB diagnosis for all the State.
      Considering that rapid and accurate diagnosis is essential for TB control, the
      aim of this study was to evaluate the use of an in-house real-time (RT)-PCR assay
      targeting the mpt64 gene in the routine diagnosis of TB, and to compare this
      technique with smear microscopy and culture. From August 2012 to October 2013,
      715 sputum samples from 657 patients were included in the study. Smear
      microscopy, culture, phenotypic and PRA-hsp65 identification of mycobacteria, and
      mpt64 RT-PCR were performed. With respect to confirmed TB cases (n = 62/657;
      9.4%), smear microscopy had a sensitivity of 82.3%. Culture and RT-PCR showed the
      same sensitivity, i.e. 90.3%. Specificity was 99.7, 99.4 and 98.6% for smear
      microscopy, culture and RT-PCR, respectively. mpt64 RT-PCR showed high
      sensitivity and specificity for the detection of Mycobacterium tuberculosis
      complex in sputum samples. This technique can be deployed in laboratories that do
      not have a rapid test for TB available, enabling the performance of TB diagnosis
      in up to 5 h.

PMID- 26297003
TI  - Pyranopterin Coordination Controls Molybdenum Electrochemistry in Escherichia
      coli Nitrate Reductase.
AB  - We test the hypothesis that pyranopterin (PPT) coordination plays a critical role
      in defining molybdenum active site redox chemistry and reactivity in the
      mononuclear molybdoenzymes. The molybdenum atom of Escherichia coli nitrate
      reductase A (NarGHI) is coordinated by two PPT-dithiolene chelates that are
      defined as proximal and distal based on their proximity to a [4Fe-4S] cluster
      known as FS0. We examined variants of two sets of residues involved in PPT
      coordination: (i) those interacting directly or indirectly with the pyran oxygen
      of the bicyclic distal PPT (NarG-Ser(719), NarG-His(1163), and NarG-His(1184));
      and (ii) those involved in bridging the two PPTs and stabilizing the oxidation
      state of the proximal PPT (NarG-His(1092) and NarG-His(1098)). A S719A variant
      has essentially no effect on the overall Mo(VI/IV) reduction potential, whereas
      the H1163A and H1184A variants elicit large effects (DeltaEm values of -88 and 
      36 mV, respectively). Ala variants of His(1092) and His(1098) also elicit large
      DeltaEm values of -143 and -101 mV, respectively. An Arg variant of His(1092)
      elicits a small DeltaEm of +18 mV on the Mo(VI/IV) reduction potential. There is
      a linear correlation between the molybdenum Em value and both enzyme activity and
      the ability to support anaerobic respiratory growth on nitrate. These data
      support a non-innocent role for the PPT moieties in controlling active site metal
      redox chemistry and catalysis.

PMID- 26297004
TI  - Is there a threshold level of maternal education sufficient to reduce child
      undernutrition? Evidence from Malawi, Tanzania and Zimbabwe.
AB  - BACKGROUND: Maternal education is strongly associated with young child nutrition
      outcomes. However, the threshold of the level of maternal education that reduces
      the level of undernutrition in children is not well established. This paper
      investigates the level of threshold of maternal education that influences child
      nutrition outcomes using Demographic and Health Survey data from Malawi (2010),
      Tanzania (2009-10) and Zimbabwe (2005-06). METHODS: The total number of children
      (weighted sample) was 4,563 in Malawi; 4,821 children in Tanzania; and 3,473
      children in Zimbabwe Demographic and Health Surveys. Using three measures of
      child nutritional status: stunting, wasting and underweight, we employ a survey
      logistic regression to analyse the influence of various levels of maternal
      education on child nutrition outcomes. RESULTS: In Malawi, 45% of the children
      were stunted, 42% in Tanzania and 33% in Zimbabwe. There were 12% children
      underweight in Malawi and Zimbabwe and 16% in Tanzania.The level of wasting was
      6% of children in Malawi, 5% in Tanzania and 4% in Zimbabwe. Stunting was
      significantly (p values < 0.0001) associated with mother's educational level in
      all the three countries. Higher levels of maternal education reduced the odds of
      child stunting, underweight and wasting in the three countries. The maternal
      threshold for stunting is more than ten years of schooling. Wasting and
      underweight have lower threshold levels. CONCLUSION: These results imply that the
      free primary education in the three African countries may not be sufficient and
      policies to keep girls in school beyond primary school hold more promise of
      addressing child undernutrition.

PMID- 26297005
TI  - Canine rotavirus C strain detected in Hungary shows marked genotype diversity.
AB  - Species C rotaviruses (RVC) have been identified in humans and animals, including
      pigs, cows and ferrets. In dogs, RVC strains have been reported anecdotally on
      the basis of visualization of rotavirus-like virions by electron microscopy
      combined with specific electrophoretic migration patterns of the genomic RNA
      segments. However, no further molecular characterization of these viruses was
      performed. Here, we report the detection of a canine RVC in the stool of a dog
      with enteritis. Analysis of the complete viral genome uncovered distinctive
      genetic features of the identified RVC strain. The genes encoding VP7, VP4 and
      VP6 were distantly related to those of other RVC strains and were putatively
      classified as G10, P8 and I8, respectively. The new strain was named RVC/Dog
      wt/HUN/KE174/2012/G10P[8]. Phylogenetic analyses revealed that canine RVC was
      most closely related to bovine RVC strains with the exception of the NSP4 gene,
      which clustered together with porcine RVC strains. These findings provide further
      evidence for the genetic diversity of RVC strains. 

PMID- 26297006
TI  - Pantoea intestinalis sp. nov., isolated from the human gut.
AB  - A novel bacterial strain, 29Y89BT, was isolated from a faecal sample of a healthy
      human subject. Cells were Gram-stain-negative, motile, non-spore-forming and rod
      shaped. Strain 29Y89BT formed cream-coloured colonies 2 mm in diameter on
      trypticase soy agar and showed optimum growth at 35  degrees C. Strain 29Y89BT
      showed highest 16S rRNA gene sequence similarity to Pantoea gaviniae A18/07T
      (98.4 %) followed by Pantoea calida 1400/07T (97.2 %). Multi-locus sequence
      analysis using atpD (ATP synthase beta subunit), gyrB (DNA gyrase), infB
      (initiation translation factor 2) and rpoB (RNA polymerase beta subunit) genes
      also supported the result of 16S rRNA gene sequence based phylogeny. Strain
      29Y89BT showed 62 and 40.7 % DNA-DNA relatedness with P. calida DSM 22759T and P.
      gaviniae DSM 22758T. Strain 29Y89BT contained C17  : 0 cyclo, C19  : 0 cyclo
      omega8c, C16 : 0, C14 : 0 and C12 : 0 as predominant fatty acids. In addition,
      strain 29Y89BT showed physiological and phenotypic differences from its closest
      relatives P. gaviniae DSM 22758T and P. calida DSM 22759T. The polar lipid
      profile mainly comprised phospholipids. The DNA G+C content was 59.1 mol%. Thus,
      based on the findings of the current study, strain 29Y89BT showed clear
      delineations from its closest relatives P. gaviniae DSM 22758T and P. calida DSM
      22759T, and is thus considered to represent a novel species of the genus Pantoea,
      for which the name Pantoea intestinalis sp. nov. is proposed. The type strain is
      29Y89BT ( = DSM 28113T = MCC 2554T). 

PMID- 26297007
TI  - Flectobacillus rhizosphaerae sp. nov., isolated from the rhizosphere soil of
      Oryza sativa (L.), and emended description of the genus Flectobacillus.
AB  - A Gram-stain-negative, aerobic, pale orange, rod-shaped, non-motile bacterial
      strain, designated JC289T was isolated from a rhizosphere soil sample of the
      plant Oryza sativa (L.). 16S rRNA gene sequence analysis clearly allocated strain
      JC289T to the Flectobacillus cluster, showing highest sequence similarities to
      Flectobacillus roseus GFA-11T (99.5 %), Flectobacillus major ATCC 29496T (96.7 %)
      and Flectobacillus lacus CL-GP79T (94.6 %). Major (>5 %) fatty acids of strain
      JC289T were C16 : 1omega5c, iso-C15 : 0, C15 : 0 2-OH, iso-C15 : 0 3-OH and C16 :
      1omega7c/C16 : 1omega6c, with minor amounts (>1- < 5 %) of C14 : 0, C16 : 0,
      anteiso-C15 : 0, C16 : 0 3-OH, iso-C17 : 0 3-OH, anteiso-C17 : 1B and/or iso-C17
      : 1I. Menaquinone-7 was the major quinone of strain JC289T, and the polar lipid
      profile contained phosphatidylethanolamine, five unidentified aminophospholipids,
      two unidentified phospholipids, two unidentified aminolipids, two unidentified
      glycolipids and five unidentified lipids. DNA-DNA relatedness values of strain
      JC289T with Flectobacillus roseus LMG 24501T and Flectobacillus major LMG 13163T
      were 24.6 % (31.4 %, reciprocal analysis) and 16.2 % (22.4 %), respectively. On
      the basis of 16S rRNA gene sequence analysis, physiological and biochemical test
      results, and chemotaxonomic analysis, strain JC289T can be differentiated from
      its closest relatives in the genus Flectobacillus. Based on the data presented,
      it is concluded that strain JC289T represents a novel species of the genus
      Flectobacillus, for which the name Flectobacillus rhizosphaerae sp. nov. is
      proposed. The type strain is JC289T ( = KCTC 42575T = LMG 28712T). 

PMID- 26297008
TI  - Aquabacterium olei sp. nov., an oil-degrading bacterium isolated from oil
      contaminated soil.
AB  - Strain NHI-1T is a Gram-negative, motile, non-spore-forming bacterium isolated
      from oil-contaminated soil in South Korea. The strain was able to grow by using
      gasoline, diesel and kerosene as energy and carbon sources. After incubation for
      14 days, cells (1 g l- 1) degraded approximately 58 % of oil present at
      concentration of 1500 p.p.m. at pH 8 and 28  degrees C. Strain NHI-1T grew well
      under aerobic conditions, with optimal growth at pH 7-9 and 28  degrees C-37 
      degrees C but grew poorly in the presence of >= 0.5 % NaCl. Phylogenetic analyses
      based on 16S rRNA gene sequences indicated that the closest relatives of strain
      NHI-1T were Aquabacterium fontiphilum CS-6T (97.96 % sequence similarity),
      Aquabacterium parvum B6T (96.39 %), Aquabacterium commune B8T (95.76 %),
      Aquabacterium limnoticum ABP-4T (95.72 %) and Aquabacterium citratiphilum B4T
      (95.25 %). DNA-DNA relatedness was 41-53 % between strain NHI-1T and its closest
      type strains. The major fatty acids present in strain NHI-1T were summed feature
      3 (C16 : 1omega7c/C16 : 1omega6c, 44.5 %), summed feature 8 (C18 : 1omega7c/C18 :
      1omega6c, 21.5 %) and C16 : 0 (16.2 %), and the predominant polar lipids were
      phosphatidylglycerol, phosphatidylethanolamine, phosphatidylserine,
      diphosphatidylglycerol and uncharacterized aminophospholipids. Strain NHI-1T was
      distinguishable from other members of genus Aquabacterium based on phenotypic,
      chemotaxonomic and genotypic characteristics. Therefore, strain NHI-1T represents
      a novel species of the genus Aquabacterium for which the name Aquabacterium olei
      sp. nov. is proposed. The type strain is NHI-1T ( = KEMB 9005-082T =  KACC 18244T
      = NBRC 110486T). 

PMID- 26297009
TI  - Zhihengliuella somnathii sp. nov., a halotolerant actinobacterium from the
      rhizosphere of a halophyte Salicornia brachiata.
AB  - Two novel, Gram-stain-positive, rod-shaped, halotolerent bacteria, strains JG
      03(T) and JG 05 were isolated from the rhizosphere of Salicornia brachiata, an
      extreme halophyte. Comparative analyses of 16S rRNA gene sequences showed that
      they were closely related to members of the genus Zhihengliuella, with sequence
      similarities of 96.9-99.1%. The sequence similarity of strains JG 03(T )and JG 05
      with each other was 99.4%. DNA-DNA hybridization of JG 03(T) and JG 05 with other
      species of the genus Zhihengliuella with validly published names showed
      reassociation values of 19.8%-53.4% and a value of 91.4% between each other. The
      peptidoglycan type of both strains was A4alpha and MK-9 and MK-10 were the
      predominant menaquinones. The predominant fatty acid in JG 03(T) was anteiso-C15
      : 0 and anteiso-C17 : 0. However, iso-C15 : 0, anteiso-C15 : 0 and anteiso-C17 :
      0 were the major fatty acids in strain JG 05. The DNA G+C content of strains JG
      03(T) and JG 05 was 70.0 and 70.1 mol%, respectively. In nutrient broth medium
      both strains grew at NaCl concentrations of up to 15% (w/v). On the basis of
      chemotaxonomic characteristics and phylogenetic analyses, strains JG 03(T) and JG
      05 should be affiliated to the genus Zhihengliuella. Strains JG 03(T) and JG 05
      represent a novel species of the genus Zhihengliuella for which the name
      Zhihengliuella somnathii sp. nov. is proposed. The type strain is JG 03(T) ( =
      DSM 23187(T) = IMCC 253(T)).

PMID- 26297010
TI  - Psychometric Properties of the Abbreviated Multidimensional Acculturation Scale
      and the Multigroup Ethnic Identity Measure With Japanese Sojourners.
AB  - The current study examined psychometric properties of the Japanese version of
      Abbreviated Multidimensional Acculturation Scale (AMAS-ZABB-JP) and the 20-item
      Multigroup Ethnic Identity Measure (MEIM-JP) with 273 Japanese sojourners and
      immigrants to the United States. The theoretical six-factor structure for the
      AMAS-JP and two-factor structure for the MEIM-JP was consistent with the
      literature. The subscales of the AMAS and MEIM showed expected patterns of
      correlation with each other and with additional variables (i.e., number of years
      in the United States), providing evidence for construct validity. Cronbach's
      alpha reflected high levels of reliability for both scales. Despite strong
      psychometric findings, there were translational and cultural-based findings that
      suggest the need for further research.

PMID- 26297011
TI  - Development and Validation of a State-Based Measure of Emotion Dysregulation.
AB  - Existing measures of emotion dysregulation typically assess dispositional
      tendencies and are therefore not well suited for study designs that require
      repeated assessments over brief intervals. The aim of this study was to develop
      and validate a state-based multidimensional measure of emotion dysregulation.
      Psychometric properties of the State Difficulties in Emotion Regulation Scale (S
      DERS) were examined in a large representative community sample of young adult
      women drawn from four sites ( N = 484). Exploratory factor analysis suggested a
      four-factor solution, with results supporting the internal consistency, construct
      validity, and predictive validity of the total scale and the four subscales:
      Nonacceptance (i.e., nonacceptance of current emotions), Modulate (i.e.,
      difficulties modulating emotional and behavioral responses in the moment),
      Awareness (i.e., limited awareness of current emotions), and Clarity (i.e.,
      limited clarity about current emotions). S-DERS scores were significantly
      associated with trait-based measures of emotion dysregulation, affect
      intensity/reactivity, experiential avoidance, and mindfulness, as well as
      measures of substance use problems. Moreover, significant associations were found
      between the S-DERS and state-based laboratory measures of emotional reactivity,
      even when controlling for the corresponding original DERS scales. Results provide
      preliminary support for the reliability and validity of the S-DERS as a state
      based measure of emotion regulation difficulties.

PMID- 26297012
TI  - Molecular and cellular characteristics of human and non-human primate multipotent
      stromal cells from the amnion and bone marrow during long term culture.
AB  - INTRODUCTION: Multipotent stromal cells (MSCs) are among the key candidates in
      regenerative medicine. However variety of MSC sources and general heterogeneity
      lead to controversial data in functional characterization. Furthermore, despite
      intensive usage as preclinical animal model, little is known about MSCs of the
      common marmoset monkey. METHODS: MSCs derived from placental amnion and bone
      marrow samples from human and common marmoset were characterized in parallel over
      12 passages to monitor similarities and significant differences (p <= 0.05,
      Student's t-test) in MSC markers and major histocompatibility complex (MHC) class
      I expression by immunohistochemistry, flow cytometry, real-time PCR, metabolic
      activity test, with special focus on pluripotency associated genes. RESULTS:
      Human and non-human primate MSCs were characterized for expression of MSC markers
      and capability of differentiation into mesenchymal lineages. MSCs could be
      cultured more than 100 days (26 passages), but metabolic activity was
      significantly enhanced in amnion vs. bone marrow MSCs. Interestingly, MHC class I
      expression is significantly reduced in amnion MSCs until passage 6 in human and
      marmoset, but not in bone marrow cells. For MSC markers, CD73 and CD105 levels
      remain unchanged in amnion MSCs and slightly decline in bone marrow at late
      passages; CD166 is significantly higher expressed in human MSCs, CD106
      significantly lower vs. marmoset. All cultured MSCs showed pluripotency marker
      expression like Oct-4A at passage 3 significantly decreasing over time (passages
      6-12) while Nanog expression was highest in human bone marrow MSCs. Furthermore,
      human MSCs demonstrated the highest Sox2 levels vs. marmoset, whereas the
      marmoset exhibited significantly higher Lin28A values. Bisulfite sequencing of
      the Oct-4 promoter region displayed fewer methylations of CpG islands in the
      marmoset vs. human. CONCLUSIONS: Little is known about MSC characteristics from
      the preclinical animal model common marmoset vs. human during long term culture.
      Studied human and common marmoset samples share many similar features such as
      most MSC markers and reduced MHC class I expression in amnion cells vs. bone
      marrow. Furthermore, pluripotency markers indicate in both species a
      subpopulation of MSCs with true 'stemness', which could explain their high
      proliferation capacity, though possessing differences between human and marmoset
      in Lin28A and Sox2 expression.

PMID- 26297013
TI  - Aestuariivita atlantica sp. nov., isolated from deep-sea sediment.
AB  - A novel strain, 22II-S11-z3T, was isolated from the deep-sea sediment of the
      Atlantic Ocean. The bacterium was aerobic, Gram-staining-negative, oxidase
      positive and catalase-negative, oval- to rod-shaped, and non-motile. Growth was
      observed at salinities of 1-9 % NaCl and temperatures of 10-45  degrees C. The
      isolate could hydrolyse aesculin and Tweens 20, 40 and 80, but not gelatin.
      Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain 22II
      S11-z3T belonged to the genus Aestuariivita, with highest sequence similarity to
      Aestuariivita boseongensis KCTC 42052T (97.5 %). The average nucleotide identity
      and digital DNA-DNA hybridization values between strain 22II-S11-z3T and A.
      boseongensis KCTC 42052T were 71.5 % and 20.0 +/- 2.3 %, respectively. The G+C
      content of the chromosomal DNA was 65.5 mol%. The principal fatty acids (>5 %)
      were summed feature 8 (C18 : 1omega7c/omega6c) (35.2 %), C19 : 0 cyclo omega8c
      (20.9 %), C16 : 0 (11.8 %), 11-methyl C18 : 1omega7c (11.4 %) and C12 : 1 3-OH
      (9.4 %). The respiratory quinone was determined to be Q-10.
      Diphosphatidylglycerol, phosphatidylcholine, phosphatidylglycerol, nine
      unidentified phospholipids, one unidentified aminolipid and two unidentified
      lipids were present. The combined genotypic and phenotypic data show that strain
      22II-S11-z3T represents a novel species of the genus Aestuariivita, for which the
      name Aestuariivita atlantica sp. nov. is proposed, with the type strain 22II-S11
      z3T ( = KCTC 42276T = MCCC 1A09432T). 

PMID- 26297014
TI  - Geographic analysis of the variation in the incidence of ADHD in a country with
      free access to healthcare: a Danish cohort study.
AB  - BACKGROUND: The prevalence of citizens diagnosed with Attention Deficit
      Hyperactivity Disorder (ADHD) has risen dramatically over the past decades in
      many countries, however, with large variations. Countries such as Denmark with
      centrally organized well fare systems, free access to health services and
      individual tracking based on unique personal identification may in particular
      contribute to our understanding of the reasons for this increase. Based on Danish
      registers we aimed to examine the geographical patterns of the distribution of
      ADHD diagnosis and medication use and explore the association with access to
      diagnostic services, diagnostic culture, neighbourhood socioeconomic status and
      municipal spending on health care for children. METHODS: We combined information
      on registered diagnosis of ICD-10 Hyperkinetic Disorder and ADHD medication use
      in a Danish register-based cohort of children born between 1990 and 2000. We
      mapped incidence proportions of diagnoses and medication use within the 98 Danish
      Municipalities. Global and local clustering of ADHD was identified using spatial
      analysis. Information on contextual factors in the municipalities was obtained
      from national registers. The associations between the incidence of ADHD and
      contextual factors were analysed using Bayesian spatial regression models.
      RESULTS: We found a considerable variation in the incidence of ADHD across the
      municipalities. Significant clustering of both high and low incidence of ADHD was
      identified and mapped using the local Moran's I. Clustering of low incidence of
      diagnosis and medication use was observed in less populated areas with limited
      diagnostic resources and in contrast clustering of high incidence in densely
      populated areas and greater diagnostic resources. When considering the spatial
      autocorrelation between neighbouring municipalities, no significant associations
      were found between ADHD and access to diagnostic services, different diagnostic
      culture, socioeconomic status at municipality level or the municipal spending on
      health care for children. CONCLUSIONS: A large geographical variation of ADHD in
      the municipalities was observed despite tax-financed and free access to
      healthcare. Although not statistically significant, results indicate that
      accessibility to diagnostic resources might explain some of the variation in ADHD
      incidence. In contrast to US studies the observed variation was not statistically
      associated to contextual factors in terms of SES, municipal spending on health
      care for children or differences in diagnostic practices.

PMID- 26297015
TI  - Interventions in health organisations to reduce the impact of adverse events in
      second and third victims.
AB  - BACKGROUND: Adverse events (AE) are also the cause of suffering in health
      professionals involved. This study was designed to identify and analyse
      organization-level strategies adopted in both primary care and hospitals in Spain
      to address the impact of serious AE on second and third victims. METHODS: A cross
      sectional study was conducted in healthcare organizations assessing: safety
      culture; health organization crisis management plans for serious AE; actions
      planned to ensure transparency in communication with patients (and relatives) who
      experience an AE; support for second victims; and protective measures to
      safeguard the institution's reputation (the third victim). RESULTS: A total of
      406 managers and patient safety coordinators replied to the survey. Deficient
      provision of support for second victims was acknowledged by 71 and 61% of the
      participants from hospitals and primary care respectively; these respondents
      reported there was no support protocol for second victims in place in their
      organizations. Regarding third victim initiatives, 35% of hospital and 43% of
      primary care professionals indicated no crisis management plan for serious AE
      existed in their organization, and in the case of primary care, there was no
      crisis committee in 34% of cases. The degree of implementation of second and
      third victim support interventions was perceived to be greater in hospitals (mean
      14.1, SD 3.5) than in primary care (mean 11.8, SD 3.1) (p < 0.001). CONCLUSIONS:
      Many Spanish health organizations do not have a second and third victim support
      or a crisis management plan in place to respond to serious AEs.

PMID- 26297016
TI  - Adhesion and biofilm formation in artificial saliva and susceptibility of yeasts
      isolated from chronic kidney patients undergoing haemodialysis.
AB  - Yeasts of the genera Candida and Saccharomyces are opportunist pathogens and
      cause oral lesions, especially in immunocompromised patients. This study assessed
      yeasts isolated from chronic kidney patients undergoing haemodialysis for their
      adhesion capacity, biofilm formation and susceptibility to antifungal agents. Ten
      isolates of Candida spp. and one isolate of Saccharomyces cerevisiae were tested
      for adhesion to buccal epithelial cells (BECs), adhesion and formation of biofilm
      in artificial saliva and their susceptibility profile to antifungal agents.
      Adhesion and biofilm formation were undertaken in polystyrene plates with
      artificial saliva, whilst susceptibility to antifungal agents was evaluated by
      broth microdilution. Candida parapsilosis had the highest adhesion index in BECs
      (154.55 +/- 22.13) and Candida rugosa was the species with the highest adhesion
      capacity (18 398  Abs cm(-2)) in abiotic surface with artificial saliva. Candida
      albicans provided the greatest biofilm formation (2035  Abs cm(-2) +/- 0.09) but
      was revealed to be susceptible to the five antifungal agents under analysis.
      However, some non-albicans Candida isolates showed a lower susceptibility for the
      antifungal agents itraconazole, fluconazole and voriconazole. All of the species
      were sensitive to amphotericin B and nystatin. The current analysis showed that
      yeasts isolated from the mouth of chronic kidney patients undergoing
      haemodialysis varied significantly with regard to their capacity for adherence,
      biofilm formation and susceptibility to antifungal agents, underscoring the high
      virulence of non-albicans Candida species.

PMID- 26297017
TI  - In vivo characterization of the scaffold activity of flotillin on the membrane
      kinase KinC of Bacillus subtilis.
AB  - Scaffold proteins are ubiquitous chaperones that bind to proteins and facilitate
      the physical interaction of the components of signal transduction pathways or
      multi-enzymic complexes. In this study, we used a biochemical approach to dissect
      the molecular mechanism of a membrane-associated scaffold protein, FloT, a
      flotillin-homologue protein that is localized in functional membrane microdomains
      of the bacterium Bacillus subtilis. This study provides unambiguous evidence that
      FloT physically binds to and interacts with the membrane-bound sensor kinase
      KinC. This sensor kinase activates biofilm formation in B. subtilis in response
      to the presence of the self-produced signal surfactin. Furthermore, we have
      characterized the mechanism by which the interaction of FloT with KinC benefits
      the activity of KinC. Two separate and synergistic effects constitute this
      mechanism: first, the scaffold activity of FloT promotes more efficient self
      interaction of KinC and facilitates dimerization into its active form. Second,
      the selective binding of FloT to KinC prevents the occurrence of unspecific
      aggregation between KinC and other proteins that may generate dead-end
      intermediates that could titrate the activity of KinC. Flotillin proteins appear
      to play an important role in prokaryotes in promoting effective binding of
      signalling proteins with their correct protein partners. 

PMID- 26297019
TI  - Management of Recurrent Catheter-Related Bloodstream Infections in an Adult
      Patient Receiving Home Parenteral Nutrition: Dramatic Effect of Ethanol Lock
      Therapy.
AB  - We report the use of ethanol lock therapy to dramatically reduce the incidence of
      catheter-related bloodstream infections (CRBSIs) in a long-term adult home
      parenteral nutrition (HPN) patient. This case study demonstrates the efficacy of
      ethanol lock therapy in eliminating CRBSIs when other treatments have been
      unsuccessful. We suggest that ethanol lock therapy has an important role in
      decreasing CRBSI in HPN patients with recurrent CRBSIs.

PMID- 26297018
TI  - A unique phenotype in a patient with a rare triplication of the 22q11.2 region
      and new clinical insights of the 22q11.2 microduplication syndrome: a report of
      two cases.
AB  - BACKGROUND: The rearrangements of the 22q11.2 chromosomal region, most frequently
      deletions and duplications, have been known to be responsible for multiple
      congenital anomaly disorders. These rearrangements are implicated in syndromes
      that have some phenotypic resemblances. While the 22q11.2 deletion, also known as
      DiGeorge/Velocardiofacial syndrome, has common features that include cardiac
      abnormalities, thymic hypoplasia, characteristic face, hypocalcemia, cognitive
      delay, palatal defects, velopharyngeal insufficiency, and other malformations,
      the microduplication syndrome is largely undetected. This is mainly because
      phenotypic appearance is variable, milder, less characteristic and unpredictable.
      In this paper, we report the clinical evaluation and follow-up of two patients
      affected by 22q11.2 rearrangements, emphasizing new phenotypic features
      associated with duplication and triplication of this genomic region. CASE
      PRESENTATION: Patient 1 is a 24 year-old female with 22q11.2 duplication who has
      a heart defect (ostium secundum atrial septal defect) and supernumerary teeth
      (hyperdontia), a feature previously not reported in patients with 22q11.2
      microduplication syndrome. Her monozygotic twin sister, who died at the age of
      one month, had a different heart defect (truncus arteriousus). Patient 2 is a 20
      year-old female with a 22q11.2 triplication who had a father with 22q11.2
      duplication. In comparison to the first case reported in the literature, she has
      an aggravated phenotype characterized by heart defects (restrictive VSD and
      membranous subaortic stenosis), and presented other facial dysmorphisms and
      urogenital malformations (ovarian cyst). Additionally, she has a hemangioma
      planum on the right side of her face, a feature of Sturge-Weber syndrome.
      CONCLUSIONS: In this report, we described hyperdontia as a new feature of 22q11.2
      microdeletion syndrome. Moreover, this syndrome was diagnosed in a patient who
      had a deceased monozygotic twin affected with a different heart defect, which
      corresponds to a phenotypic discordance never reported in the literature. Case 2
      is the second clinical report of 22q11.2 triplication and presents an aggravated
      phenotype in contrast to the patient previously reported.

PMID- 26297020
TI  - Dystocia in the cat evaluated using an insurance database.
AB  - Objectives The aim of this study was to describe the incidence of feline dystocia
      with respect to breed. Methods The data used were reimbursed claims for
      veterinary care insurance and/or life insurance claims in cats registered in a
      Swedish insurance database from 1999-2006. Results The incidence rates for
      dystocia were about 22 cats per 10,000 cat-years at risk, 67 per 10,000 for
      purebred cats and seven per 10,000 for domestic shorthair cats. The median age
      was 2.5 years. A significant effect of breed was seen. An incidence rate ratio
      (IRR) that was significantly higher compared with other purebred cats was seen in
      the British Shorthair (IRR 2.5), the Oriental group (IRR 2.2), Birman (IRR 1.7),
      Ragdoll (IRR 1.5) and the Abyssinian group (IRR 1.5). A significantly lower IRR
      was seen in the Norwegian Forest Cat (IRR 0.38), the Maine Coon (IRR 0.48), the
      Persian/Exotic group (IRR 0.49) and the Cornish Rex (IRR 0.50). No common factor
      among the high-risk breeds explained their high risk for dystocia. There was no
      effect of location; that is, the incidence rate did not differ depending on
      whether the cat lived in an urban or rural area. Caesarean section was performed
      in 56% of the cats with dystocia, and the case fatality was 2%. Conclusions and
      relevance The incidence rate for dystocia was of a similar magnitude in purebred
      cats as in dogs. The IRR varied significantly among breeds, and the main cause
      for dystocia should be identified separately for each breed. A selection for easy
      parturitions in breeding programmes is suggested.

PMID- 26297021
TI  - Postpartum uterus involution observed by real-time ultrasound scanning and
      vaginal cytology in Van cats.
AB  - OBJECTIVES: The objective was to investigate postpartum uterus involution by real
      time ultrasonography and vaginal cytology in Van cats. METHODS: This study
      included 15 healthy Van cats belonging to the Van Cat Research Centre (Yuzuncu
      Yil University, Van, Turkey). Starting 24 h postpartum, ultrasonographic
      measurements were performed on the placental and interplacental uterine horn
      regions every day. Decreases in the diameters and uterine content were considered
      as criteria for uterine involution. Vaginal discharge samples were collected
      every day for 4 weeks postpartum. The smears were stained with Papanicolaou
      stain. RESULTS: The average diameters of placental and interplacental regions
      (IPRs) in the uterine horns were 3.12 +/- 0.29 cm and 2.36 +/- 0.43 cm,
      respectively, at 24 h postpartum. Placental regions (PRs) shrank faster than
      IPRs. At 48 h postpartum, it became difficult to distinguish PRs from IPRs in the
      uterine horns. The uterine horns could be seen in the abdominal cavity up to 5.60
      +/- 0.99 days postpartum. The mean of the last assessable diameter of the uterine
      horns from days 4 to 7 in all cats was 0.49 +/- 0.07 cm. The vaginal epithelial
      cells appeared to be under the effect of oestrogen for 4 weeks postpartum.
      CONCLUSIONS AND RELEVANCE: The morphological involution of the uterus completes,
      to a large extent, within the first 48 h postpartum in Van cats. A more detailed
      hormonal analysis would contribute greatly to the understanding of the
      physiological processes involved in this period. Although postpartum involution
      appeared complete by 5.60 +/- 0.99 days after parturition in Van cats,
      histological verification of this finding is needed.

PMID- 26297022
TI  - Alkalimarinus sediminis gen. nov., sp. nov., isolated from marine sediment.
AB  - Strain FA028T, a beige-pigmented, facultatively anaerobic, heterotrophic,
      catalase-negative and oxidase-positive, Gram-stain-negative bacterium, was
      isolated from marine sediment of the coast of Weihai, China. Cells of strain
      FA028T were rod-shaped, 1-3 MUm in length and 0.5 MUm in width. The strain was
      able to grow at 13-37  degrees C, at pH 7.0-9.5 and in the presence of 1.0-4.0 %
      (w/v) NaCl. Optimal growth was observed at 28  degrees C, with 3.0 % NaCl and at
      pH 7.5-8.0. Nitrate was not reduced. The G+C content of the DNA was 43.4 mol%.
      The isoprenoid quinone was Q-9 and the main cellular fatty acids (>10 %) were C16
      : 0, C16 : 1omega9c and iso-C15 : 0 2-OH/C16 : 1omega7c. The major polar lipids
      in strain FA028T were phosphatidylglycerol, phosphatidylethanolamine and
      diphosphatidylglycerol; phospholipid was present in moderate to minor amounts in
      the polar lipid profile. Phylogenetic analysis based on 16S rRNA gene sequences
      revealed that strain FA028T was affiliated with the phylum Proteobacteria. 16S
      rRNA gene sequence comparisons showed that this isolate is unique, sharing < 93 %
      similarity with species of the families Alteromonadaceae and Oceanospirillaceae.
      On the basis of the phenotypic and phylogenetic data, strain FA028T should be
      classified as representing a novel species of a new genus within the family
      Alteromonadaceae, for which the name Alkalimarinus sediminis gen. nov., sp. nov.
      is proposed. The type strain of Alkalimarinus sediminis is FA028T ( = CICC 10906T
      = KCTC 42258T).

PMID- 26297023
TI  - Spirosoma fluviale sp. nov., isolated from river water.
AB  - A bacterial strain, designated MSd3T, was isolated from a freshwater sample
      collected from the Hosoda River in Japan. The cells of strain MSd3T were Gram
      stain-negative, non-spore-forming, aerobic, non-motile, curved rods forming
      rings, coils and undulating filaments. The 16S rRNA gene sequence of strain MSd3T
      showed closest similarity to that of Spirosoma linguale DSM 74T (97.6 %
      similarity) and similarity to other members of the genus Spirosoma ranged from
      90.3 to 95.9 %. Strain MSd3T contained menaquinone 7 as the sole respiratory
      quinone. The major cellular fatty acids were summed feature 3 (C16 : 1omega6c
      and/or C16 : 1omega7c) and C16 : 1omega5c. The polar lipids were
      phosphatidylethanolamine, three unidentified aminophospholipids and three
      unidentified polar lipids. The DNA G+C content was 53.3 mol%. The DNA-DNA
      relatedness between strain MSd3T and S. linguale DSM 74T was 19 % or 25 %
      (reciprocal value). From the chemotaxonomic and physiological data and the levels
      of DNA-DNA relatedness, strain MSd3T should be classified as the representative
      of a novel species of the genus Spirosoma, for which the name Spirosoma fluviale
      sp. nov. (type strain MSd3T = JCM 30659T = DSM 29961T) is proposed. 

PMID- 26297024
TI  - In vitro activity of colistin in antimicrobial combination against carbapenem
      resistant Acinetobacter baumannii isolated from patients with ventilator
      associated pneumonia in Vietnam.
AB  - Acinetobacter baumannii has become one of the major infection threats in
      intensive care units (ICUs) globally. Since 2008, A. baumannii has been the
      leading cause of ventilator-associated pneumonia (VAP) in our ICU at an
      infectious disease hospital in southern Vietnam. The emergence of this pathogen
      in our setting is consistent with the persistence of a specific clone exhibiting
      resistance to carbapenems. Antimicrobial combinations may be a strategy to treat
      infections caused by these carbapenem-resistant A. baumannii. Therefore, we
      assessed potential antimicrobial combinations against local carbapenem-resistant
      A. baumannii by measuring in vitro interactions of colistin with four
      antimicrobials that are locally certified for treating VAP. We first performed
      antimicrobial susceptibility testing and multilocus variable number tandem repeat
      analysis (MLVA) genotyping on 74 A. baumannii isolated from quantitative tracheal
      aspirates from patients with VAP over an 18-month period. These 74 isolates could
      be subdivided into 21 main clusters by MLVA and >80 % were resistant to
      carbapenems. We selected 56 representative isolates for in vitro combination
      synergy testing. Synergy was observed in four (7 %), seven (13 %), 20 (36 %) and
      38 (68 %) isolates with combinations of colistin with ceftazidime, ceftriaxone,
      imipenem and meropenem, respectively. Notably, more carbapenem-resistant A.
      baumannii isolates (36/43; 84 %) exhibited synergistic activity with a
      combination of colistin and meropenem than carbapenem-susceptible A. baumannii
      isolates (2/13; 15 %) (P = 0.023; Fisher's exact test). Our findings suggest that
      combinations of colistin and meropenem should be considered when treating
      carbapenem-resistant A. baumannii infections in Vietnam, and we advocate clinical
      trials investigating combination therapy for VAP. 

PMID- 26297025
TI  - Two NAC transcription factors from Caragana intermedia altered salt tolerance of
      the transgenic Arabidopsis.
AB  - BACKGROUND: Plants are continuously challenged by different environment stresses,
      and they vary widely in their adjustability. NAC (NAM, ATAF and CUC)
      transcription factors are known to be crucial in plants tolerance response to
      abiotic stresses, such as drought and salinity. ANAC019, ANAC055, and ANAC072,
      belong to the stress-NAC TFs, confer the Arabidopsis abiotic stress tolerance.
      RESULTS: Here we isolated two stress-responsive NACs, CiNAC3 and CiNAC4, from
      Caragana intermedia, which were induced by ABA and various abiotic stresses.
      Localization assays revealed that CiNAC3 and CiNAC4 localized in the nuclei,
      consistent with their roles as transcription factors. Histochemistry assay using
      Pro(CiNAC4)::GUS transgenic Arabidopsis showed that the expression of the GUS
      reporter was observed in many tissues of the transgenic plants, especially in the
      root vascular system. Overexpression of CiNAC3 and CiNAC4 reduced ABA sensitivity
      during seed germination, and enhanced salt tolerance of the transgenic
      Arabidopsis. CONCLUSIONS: We characterised CiNAC3 and CiNAC4 and found that they
      were induced by numerous abiotic stresses and ABA. GUS histochemical assay of
      CiNAC4 promoter suggested that root, flower and local damaged tissues were the
      strongest stained tissues. Overexpression assay revealed that CiNAC4 play
      essential roles not only in promoting lateral roots formation, but also in
      responding to salinity and ABA treatment of Arabidopsis.

PMID- 26297026
TI  - Insulin and IGF1 signalling pathways in human astrocytes in vitro and in vivo;
      characterisation, subcellular localisation and modulation of the receptors.
AB  - BACKGROUND: The insulin/IGF1 signalling (IIS) pathways are involved in longevity
      regulation and are dysregulated in neurons in Alzheimer's disease (AD). We
      previously showed downregulation in IIS gene expression in astrocytes with AD
      neuropathology progression, but IIS in astrocytes remains poorly understood. We
      therefore examined the IIS pathway in human astrocytes and developed models to
      reduce IIS at the level of the insulin or the IGF1 receptor (IGF1R). RESULTS: We
      determined IIS was present and functional in human astrocytes by immunoblotting
      and showed astrocytes express the insulin receptor (IR)-B isoform of Ir.
      Immunocytochemistry and cell fractionation followed by western blotting revealed
      the phosphorylation status of insulin receptor substrate (IRS1) affects its
      subcellular localisation. To validate IRS1 expression patterns observed in
      culture, expression of key pathway components was assessed on post-mortem AD and
      control tissue using immunohistochemistry. Insulin signalling was impaired in
      cultured astrocytes by treatment with insulin + fructose and resulted in
      decreased IR and Akt phosphorylation (pAkt S473). A monoclonal antibody against
      IGF1R (MAB391) induced degradation of IGF1R receptor with an associated decrease
      in downstream pAkt S473. Neither treatment affected cell growth or viability as
      measured by MTT and Cyquant(r) assays or GFAP immunoreactivity. DISCUSSION: IIS
      is functional in astrocytes. IR-B is expressed in astrocytes which differs from
      the pattern in neurons, and may be important in differential susceptibility of
      astrocytes and neurons to insulin resistance. The variable presence of IRS1 in
      the nucleus, dependent on phosphorylation pattern, suggests the function of
      signalling molecules is not confined to cytoplasmic cascades. Down-regulation of
      IR and IGF1R, achieved by insulin + fructose and monoclonal antibody treatments,
      results in decreased downstream signalling, though the lack of effect on
      viability suggests that astrocytes can compensate for changes in single pathways.
      Changes in signalling in astrocytes, as well as in neurons, may be important in
      ageing and neurodegeneration.

PMID- 26297027
TI  - Maribacter confluentis sp. nov., isolated from the junction between the ocean and
      a freshwater spring.
AB  - A Gram-stain-negative, aerobic, non-spore-forming, non-flagellated, non-gliding
      and rod-shaped bacterial strain, SSK2-2(T), was isolated from the place where the
      ocean and a freshwater spring meet at Jeju island, South Korea. Strain SSK2-2(T)
      grew optimally at 30  degrees C, at pH 7.0-8.0 and in the presence of 2.0-3.0%
      (w/v) NaCl. The neighbour-joining phylogenetic tree based on 16S rRNA gene
      sequences revealed that strain SSK2-2(T) fell within the clade comprising the
      type strains of species of the genus Maribacter, joining the type strain of
      Maribacter sedimenticola with which it shared 99.4% similarity. Sequence
      similarities to the type strains of other Maribacter species were 94.6-98.2%.
      Strain SSK2-2(T) contained MK-6 as the predominant menaquinone and iso-C17 : 0 3
      OH, iso-C15 : 0, iso-C15 : 1 G, summed feature 3 (C16 : 1omega7c and/or C16 :
      1omega6c) and summed feature 9 (iso-C17 : 1omega9c and/or 10-methyl C16 : 0) as
      the major fatty acids. The major polar lipids of strain SSK2-2(T) were
      phosphatidylethanolamine and one unidentified lipid. The DNA G+C content of
      strain SSK2-2(T) was 38.2 mol% and mean levels of DNA-DNA relatedness with the
      type strains of four phylogenetically related species of the genus Maribacter
      were 11-24%. Differential phenotypic properties, together with phylogenetic and
      genetic distinctiveness, revealed that strain SSK2-2(T) is separate from other
      Maribacter species. On the basis of the data presented, strain SSK2-2(T) is
      considered to represent a novel species of the genus Maribacter, for which the
      name Maribacter confluentis sp. nov. is proposed. The type strain is SSK2-2(T) (
      = KCTC 42604(T) = CECT 8869(T)).

PMID- 26297028
TI  - CYP17A1 Enzyme Activity Is Linked to Ambulatory Blood Pressure in a Family-Based
      Population Study.
AB  - BACKGROUND: Genome-wide association studies have linked CYP17A1 coding for the
      steroid hormone synthesizing enzyme 17alpha-hydroxylase (CYP17A1) to blood
      pressure (BP). We hypothesized that the genetic signal may translate into a
      correlation of ambulatory BP (ABP) with apparent CYP17A1 activity in a family
      based population study and estimated the heritability of CYP17A1 activity.
      METHODS: In the Swiss Kidney Project on Genes in Hypertension, day and night
      urinary excretions of steroid hormone metabolites were measured in 518
      participants (220 men, 298 women), randomly selected from the general population.
      CYP17A1 activity was assessed by 2 ratios of urinary steroid metabolites: one
      estimating the combined 17alpha-hydroxylase/17,20-lyase activity (ratio 1) and
      the other predominantly 17alpha-hydroxylase activity (ratio 2). A mixed linear
      model was used to investigate the association of ABP with log-transformed CYP17A1
      activities exploring effect modification by urinary sodium excretion. RESULTS:
      Daytime ABP was positively associated with ratio 1 under conditions of high, but
      not low urinary sodium excretion (P interaction <0.05). Ratio 2 was not
      associated with ABP. Heritability estimates (SE) for day and night CYP17A1
      activities were 0.39 (0.10) and 0.40 (0.09) for ratio 1, and 0.71 (0.09) and 0.55
      (0.09) for ratio 2 (P values <0.001). CYP17A1 activities, assessed with ratio 1,
      were lower in older participants. CONCLUSIONS: Low apparent CYP17A1 activity
      (assessed with ratio 1) is associated with elevated daytime ABP when salt intake
      is high. CYP17A1 activity is heritable and diminished in the elderly. These
      observations highlight the modifying effect of salt intake on the association of
      CYP17A1 with BP.

PMID- 26297029
TI  - Effects of Resistance Training With and Without Caloric Restriction on Arterial
      Stiffness in Overweight and Obese Older Adults.
AB  - BACKGROUND: Arterial stiffness is an important marker of vascular aging that is
      increased in sedentary, obese older adults. Weight loss induced by caloric
      restriction (CR) can improve arterial stiffness in this population; however, the
      effects of resistance training (RT) are not clear. This pilot study determined
      the effects of RT with and without CR on arterial stiffness in overweight and
      obese older adults. METHODS: Participants (mean age = 68+/-3 years, mean body
      mass index = 31.1+/-2.7 kg/m(2), 56% female, 13% Black) were randomly assigned to
      3 days/week of supervised moderate-intensity RT (n = 16) or RT+CR (n = 16) for 5
      months. Three indices of arterial stiffness were measured: brachial-ankle pulse
      wave velocity, large artery elasticity, and small artery elasticity. RESULTS:
      Body mass was significantly reduced in the RT+CR group compared to the RT group (
      6.2+/-4.8 vs. 0.2+/-1.2 kg, P = 0.0006). Within-group analyses showed that none
      of the arterial stiffness measures changed with RT or RT+CR. There were also no
      significant between-group differences, though median changes in large artery
      elasticity were slightly greater with RT+CR: 0.7 (-2.5, 5.1) vs. 0.3 (-2.6, 0.9)
      ml/mm Hg * 10, P = 0.07. Changes in large artery elasticity were negatively
      correlated with changes in waist circumference (r = -0.36, P < 0.05), systolic
      blood pressure (r = -0.38, P = 0.03), and diastolic blood pressure (r = -0.41, P
      = 0.02). CONCLUSIONS: The combination of RT and CR, leading to a modest amount of
      weight loss (7%), tended to increase large artery elasticity more than RT alone.
      Our data suggest that reductions in waist circumference and blood pressure may
      promote improvements in elasticity. CLINICAL TRIALS REGISTRATION: Trial Number
      NCT01049698.

PMID- 26297030
TI  - Brachial Pressure Control Fails to Account for Most Distending Pressure
      Independent, Age-Related Aortic Hemodynamic Changes in Adults.
AB  - BACKGROUND: Although several characteristics of aortic function, which are
      largely determined by age, predict outcomes beyond brachial blood pressure (BP),
      the extent to which brachial BP control accounts for age-related variations in
      aortic function is uncertain. We aimed to determine the extent to which brachial
      BP control in the general population (systolic/diastolic BP < 140/90 mm Hg)
      accounts for age-related aortic hemodynamic changes across the adult lifespan.
      METHODS: Central aortic pulse pressure (PPc), backward wave pressure (Pb), pulse
      wave velocity (PWV), and PP amplification (PPamp) (applanation tonometry and
      SphygmoCor software) were determined in 1,185 participants from a community
      sample (age >16 years; 36.4% uncontrolled BP). RESULTS: With adjustments for
      distending pressure (mean arterial pressure, MAP), no increases in PPc, Pb, or
      PWV and decreases in PPamp were noted in those with an uncontrolled brachial BP
      younger than 50 years. In those older than 50 years with an uncontrolled brachial
      BP, MAP-adjusted aortic hemodynamic variables were only modestly different to
      those with a controlled brachial BP (PPc, 46+/-14 vs. 42+/-15 mm Hg, P < 0.02,
      Pb, 23+/-8 vs. 21+/-8 mm Hg, PWV, 8.42+/-3.21 vs. 8.19+/-3.37 m/second, PPamp,
      1.21+/-0.17 vs. 1.21+/-0.14). Nonetheless, with adjustments for MAP, marked age
      related increases in PPc, Pb, and PWV and decreases in PPamp were noted in those
      with uncontrolled and controlled brachial BP across the adult lifespan (P <
      0.0001). CONCLUSION: Brachial BP control in the general population fails to
      account for most distending pressure-independent, age-related changes in aortic
      hemodynamics across the adult lifespan.

PMID- 26297031
TI  - Altered ENaC is Associated With Aortic Baroreceptor Dysfunction in Chronic Heart
      Failure.
AB  - BACKGROUND: Abnormal baroreceptor function contributes to attenuated arterial
      baroreflex sensitivity in chronic heart failure (CHF). As a mechanosensor in
      mammalian nonepithelium, the epithelial sodium channel (ENaC) is an amiloride
      sensitive and voltage-independent ion channel. The ENaC is thought to be a
      component of baroreceptor mechanosensitive ion channels in aortic baroreceptor
      cell bodies and nerve terminals. In this study, therefore, we measured the
      expression and activation of the ENaC in nodose neuronal cell bodies and aortic
      baroreceptor nerve terminals in sham and CHF rats. METHODS AND RESULTS: CHF was
      induced by surgical ligation of left coronary artery. The development of CHF was
      confirmed by hemodynamic and morphological characteristics. The aortic
      baroreceptor sensitivity was blunted in anesthetized CHF rats, compared with that
      in sham rats. The data from immunostaining and western blot analysis showed that
      the protein of beta- and gamma-ENaC subunits was expressed in nodose neuronal
      cell bodies and aortic baroreceptor nerve terminals, whereas the protein of alpha
      ENaC subunit was undetectable. CHF reduced protein expression of beta- and gamma
      ENaC subunits in nodose neuronal cell bodies and aortic baroreceptor nerve
      terminals. Additionally, the data recorded by the whole cell patch-clamp
      technique demonstrated that ENaC currents in aortic baroreceptor neurons were
      lower in CHF rats than that in sham rats. CONCLUSION: These results suggest that
      reduced protein expression of the ENaC decreases the ENaC activation, which could
      be involved in attenuation of the aortic baroreceptor sensitivity in the CHF
      state. Baroreceptors should be a potential therapeutic target for reducing
      mortality in CHF.

PMID- 26297032
TI  - Lactobacillus vespulae sp. nov., isolated from gut of a queen wasp (Vespula
      vulgaris).
AB  - A Gram-stain-positive, oxidase- and catalase-negative, rod-shaped, facultatively
      anaerobic bacterial strain, DCY75T, was isolated from a queen wasp (Vespula
      vulgaris). Growth occurred at 4-37  degrees C (optimum, 30  degrees C), at pH 3.5
      8.0 (optimum, pH 5.0-6.0) and with <= 7.0 % (w/v) NaCl. Strain DCY75T produced
      gas during growth on glucose. Phylogenetic analysis based on 16S rRNA gene
      sequences indicated that strain DCY75T belonged to the genus Lactobacillus and
      was closely related to Lactobacillus sanfranciscensis ATCC 27651T and
      Lactobacillus lindneri DSM 20690T at sequence similarities of 96.7 and 96.4 %,
      respectively. A comparison of two housekeeping genes, pheS and rpoA, revealed
      that strain DCT75T was well separated from other species of the genus
      Lactobacillus. Strain DCY75T produced d- and l-lactic acid isomers in a ratio of
      22.5 : 77.5 (v/v). The major fatty acids were summed feature 8 (comprising C18 : 
      1omega7c and/or C18 : 1omega6c), C16 : 0, C18 : 1omega9c and C18 : 0.The
      peptidoglycan structure was of the A4alpha (l-Lys-d-Asp) type. Cell-wall sugars
      were glucose, galactose and ribose. The DNA G+C content was 35.5 +/- 1.3 mol%.
      Based on phenotypic and genotypic properties, strain DCY75T represents a novel
      species of the genus Lactobacillus, for which the name Lactobacillus vespulae sp.
      nov. is proposed. The type strain is DCY75T ( = KCTC 21023T = JCM 19742T).

PMID- 26297033
TI  - Guidelines for diagnosing and managing paediatric concussion: Ontario Neurotrauma
      Foundation guideline.

PMID- 26297034
TI  - Contraception for adolescents (American Academy of Pediatrics).

PMID- 26297035
TI  - KU80, a key factor for non-homologous end-joining, retards geminivirus
      multiplication.
AB  - KU80 is well-known as a key component of the non-homologous end-joining pathway
      used to repair DNA double-strand breaks. In addition, the KU80-containing DNA
      dependent protein kinase complex in mammals can act as a cytoplasmic sensor for
      viral DNA to activate innate immune response. We have now, to our knowledge for
      the first time, demonstrated that the speed of a systemic infection with a plant
      DNA geminivirus in Arabidopsis thaliana is KU80-dependent. The early emergence of
      Euphorbia yellow mosaic virus DNA was significantly increased in ku80 knockout
      mutants compared with wild-type sibling controls. The possible impact of KU80 on
      geminivirus multiplication by generating non-productive viral DNAs or its role as
      a pattern-recognition receptor against DNA virus infection is discussed. 

PMID- 26297036
TI  - Carboxylicivirga linearis sp. nov., isolated from a sea cucumber culture pond.
AB  - A yellow-pigmented, Gram-stain-negative and facultatively anaerobic bacterium,
      designated FB218T, was isolated from a sediment sample collected from a sea
      cucumber culture pond in Rongcheng, China (36 degrees  54' 36" N 122 degrees  14'
      34" E). Cells of strain FB218T were slender, gliding, catalase-positive and
      oxidase-negative. Optimal growth occurred at 30  degrees C, pH 6.5-7.0 and in
      medium containing 2-3 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene
      sequences showed that strain FB218T belonged to the genus Carboxylicivirga,
      family Marinilabiliaceae. The predominant fatty acids were iso-C15 : 0 and
      anteiso-C15 : 0. MK-7 was the main respiratory quinone. The major polar lipids of
      strain FB218T were two unidentified lipids and a phospholipid. The genomic DNA
      G+C content was 40.0 mol%. Based on the distinct phylogenetic position and the
      combination of physiological and phenotypic characteristics, strain FB218T
      represents a novel species of the genus Carboxylicivirga, for which the name
      Carboxylicivirga linearis sp. nov. is proposed. The type strain is FB218T ( =
      KCTC 42254T = MCCC 1H00106T). An emended description of the genus
      Carboxylicivirga is also provided.

PMID- 26297039
TI  - Overexpression and mutation as a genetic mechanism of fluconazole resistance in
      Candida albicans isolated from human immunodeficiency virus patients in
      Indonesia.
AB  - Fluconazole is the standard treatment for oropharyngeal candidiasis, which is the
      third most common opportunistic infection in human immunodeficiency virus
      (HIV)/AIDS patients in Indonesia. Overuse of this drug could lead to the
      emergence of resistance. The objective of this study was to analyse the role of
      ERG11, CDR1, CDR2 and MDR1 gene overexpression and mutations in the ERG11 gene as
      a genetic mechanism of fluconazole resistance in Candida albicans isolated from
      HIV patients in Indonesia. Overexpression of ERG11, CDR1, CDR2 and MDR1 was
      analysed by real-time reverse transcription PCR, while ERG11 gene mutation
      analysis was performed using sequencing methods. Seventeen isolates out of 92
      strains of C. albicans isolated from 108 HIV patients were found to be resistant
      to azole antifungals. The highest gene overexpression of ERG11 was found in C.
      albicans resistant to single fluconazole, while the highest gene overexpression
      of CDR2 was detected in all isolates of C. albicans resistant to multiple azoles.
      Amino acid substitutions were observed at six positions, i.e. D116E, D153E,
      I261V, E266D, V437I and V488I. The amino acid substitution I261V was identified
      in this study and was probably associated with fluconazole resistance. The
      combination of overexpression of CDR2 and ERG11 and mutation in the ERG11 gene
      was found to be a genetic mechanism of fluconazole resistance in C. albicans
      isolated from HIV patients in Indonesia. 

PMID- 26297040
TI  - Dysgonomonas alginatilytica sp. nov., an alginate-degrading bacterium isolated
      from a microbial consortium.
AB  - Gram-stain-negative, facultatively anaerobic, non-motile, non-spore-forming, rod
      shaped bacterium, designated strain HUA-2T, was isolated from an alginate
      degrading microbial consortium. Strain HUA-2T was related to Dysgonomonas
      capnocytophagoides JCM 16697T, Dysgonomonas macrotermitis JCM 19375T and
      Dysgonomonas mossii CCUG 43457T with 95.1 %, 94.1 % and 92.1 % 16S rRNA gene
      sequence similarity, respectively. The optimal growth temperature and pH for
      strain HUA-2T were 35  degrees C and pH 8.0, respectively. Enzyme production,
      major fermentation products from glucose, and the major cellular fatty acids were
      different from those of D. capnocytophagoides CCUG 17966T or other members of the
      genus Dysgonomonas. Therefore, strain HUA-2T is proposed to represent a novel
      species of the genus Dysgonomonas, for which we propose the name Dysgonomonas
      alginatilytica sp. nov. The type strain is HUA-2T ( = DSM 100214T = HUT 8134T).

PMID- 26297038
TI  - Defining the content and delivery of an intervention to Change AdhereNce to
      treatment in BonchiEctasis (CAN-BE): a qualitative approach incorporating the
      Theoretical Domains Framework, behavioural change techniques and stakeholder
      expert panels.
AB  - BACKGROUND: Low patient adherence to treatment is associated with poorer health
      outcomes in bronchiectasis. We sought to use the Theoretical Domains Framework
      (TDF) (a framework derived from 33 psychological theories) and behavioural change
      techniques (BCTs) to define the content of an intervention to change patients'
      adherence in bronchiectasis (Stage 1 and 2) and stakeholder expert panels to
      define its delivery (Stage 3). METHODS: We conducted semi-structured interviews
      with patients with bronchiectasis about barriers and motivators to adherence to
      treatment and focus groups or interviews with bronchiectasis healthcare
      professionals (HCPs) about their ability to change patients' adherence to
      treatment. We coded these data to the 12 domain TDF to identify relevant domains
      for patients and HCPs (Stage 1). Three researchers independently mapped relevant
      domains for patients and HCPs to a list of 35 BCTs to identify two lists (patient
      and HCP) of potential BCTs for inclusion (Stage 2). We presented these lists to
      three expert panels (two with patients and one with HCPs/academics from across
      the UK). We asked panels who the intervention should target, who should deliver
      it, at what intensity, in what format and setting, and using which outcome
      measures (Stage 3). RESULTS: Eight TDF domains were perceived to influence
      patients' and HCPs' behaviours: Knowledge, Skills, Beliefs about capability,
      Beliefs about consequences, Motivation, Social influences, Behavioural regulation
      and Nature of behaviours (Stage 1). Twelve BCTs common to patients and HCPs were
      included in the intervention: Monitoring, Self-monitoring, Feedback, Action
      planning, Problem solving, Persuasive communication, Goal/target
      specified:behaviour/outcome, Information regarding behaviour/outcome, Role play,
      Social support and Cognitive restructuring (Stage 2). Participants thought that
      an individualised combination of these BCTs should be delivered to all patients,
      by a member of staff, over several one-to-one and/or group visits in secondary
      care. Efficacy should be measured using pulmonary exacerbations, hospital
      admissions and quality of life (Stage 3). CONCLUSIONS: Twelve BCTs form the
      intervention content. An individualised selection from these 12 BCTs will be
      delivered to all patients over several face-to-face visits in secondary care.
      Future research should focus on developing physical materials to aid delivery of
      the intervention prior to feasibility and pilot testing. If effective, this
      intervention may improve adherence and health outcomes for those with
      bronchiectasis in the future.

PMID- 26297037
TI  - SORT1 Mutation Resulting in Sortilin Deficiency and p75(NTR) Upregulation in a
      Family With Essential Tremor.
AB  - *These authors contributed equally to this work.Essential tremor (ET) is the most
      prevalent movement disorder affecting millions of people in the United States.
      Although a positive family history is one of the most important risk factors for
      ET, the genetic causes of ET remain unknown. In this study, whole exome
      sequencing and subsequent approaches were performed in a family with an autosomal
      dominant form of early-onset ET. Functional analyses including mutagenesis, cell
      culture, gene expression, enzyme-linked immunosorbent, and apoptosis assays were
      also performed. A disease-segregating mutation (p.Gly171Ala), absent in normal
      population, was identified in the SORT1 gene. The p.Gly171Ala mutation was shown
      not only to impair the expression of its encoding protein sortilin but also the
      mRNA levels of its binding partner p75 neurotrophin receptor that is known to be
      implicated in brain injury, neuronal apoptosis, and neurotransmission. 

PMID- 26297041
TI  - Rhizobium ecuadorense sp. nov., an indigenous N2-fixing symbiont of the
      Ecuadorian common bean (Phaseolus vulgaris L.) genetic pool.
AB  - There are two major centres of genetic diversification of common bean (Phaseolus
      vilgaris L.), the Mesoamerican and the Andean, and the legume is capable of
      establishing nitrogen-fixing symbioses with several rhizobia; Rhizobium etli
      seems to be the dominant species in both centres. Another genetic pool of common
      bean, in Peru and Ecuador, is receiving increasing attention, and studies of
      microsymbionts from the region can help to increase our knowledge about
      coevolution of this symbiosis. We have previously reported several putative new
      lineages from this region and here present data indicating that strains belonging
      to one of them, PEL4, represent a novel species. Based on 16S rRNA gene sequence
      phylogeny, PEL4 strains are positioned in the Rhizobium phaseoli/R.
      etli/Rhizobium leguminosarum clade, but show unique properties in several
      morphological, physiological and biochemical analyses, as well as in BOX-PCR
      profiles ( < 75% similarity with related species). PEL4 strains also differed
      from related species based on multilocus sequence analysis of three housekeeping
      genes (glnII, gyrB and recA). Nucleotide identities of the three concatenated
      genes between PEL4 strains and related species ranged from 91.8 to 94.2%, being
      highest with Rhizobium fabae. DNA-DNA hybridization ( < 47% DNA relatedness) and
      average nucleotide identity values of the whole genomes ( < 90.2%) also supported
      the novel species status. The PEL4 strains were effective in nodulating and
      fixing N2 with common beans. The data supported the view that PEL4 strains
      represent a novel species, Rhizobium ecuadorense sp. nov. The type strain is
      CNPSo 671(T) ( = UMR 1450(T) = PIMAMPIRS I 5(T) = LMG 27578(T)).

PMID- 26297042
TI  - Evaluation of marine subareas of Europe using life history parameters and trophic
      levels of selected fish populations.
AB  - European marine waters include four regional seas that provide valuable ecosystem
      services to humans, including fish and other seafood. However, these marine
      environments are threatened by pressures from multiple anthropogenic activities
      and climate change. The European Marine Strategy Framework Directive (MSFD) was
      adopted in 2008 to achieve good environmental status (GEnS) in European Seas by
      year 2020, using an Ecosystem Approach. GEnS is to be assessed using 11
      descriptors and up to 56 indicators. In the present analysis two descriptors
      namely "commercially exploited fish and shellfish populations" and "food webs"
      were used to evaluate the status of subareas of FAO 27 area. Data on life history
      parameters, trophic levels and fisheries related data of cod, haddock, saithe,
      herring, plaice, whiting, hake and sprat were obtained from the FishBase online
      database and advisory reports of International Council for the Exploration of the
      Sea (ICES). Subareas inhabited by r and K strategists were identified using
      interrelationships of life history parameters of commercially important fish
      stocks. Mean trophic level (MTL) of fish community each subarea was calculated
      and subareas with species of high and low trophic level were identified. The Fish
      in Balance (FiB) index was computed for each subarea and recent trends of FiB
      indices were analysed. The overall environmental status of each subarea was
      evaluated considering life history trends, MTL and FiB Index. The analysis showed
      that subareas I, II, V, VIII and IX were assessed as "good" whereas subareas III,
      IV, VI and VII were assessed as "poor". The subareas assessed as "good" were
      subject to lower environmental pressures, (less fishing pressure, less
      eutrophication and more water circulation), while the areas with "poor"
      environment experienced excessive fishing pressure, eutrophication and disturbed
      seabed. The evaluation was based on two qualitative descriptors ("commercially
      exploited fish and shellfish populations" and "food webs") is therefore more
      robust. 

PMID- 26297043
TI  - Short-term effects on antioxidant enzymes and long-term genotoxic and
      carcinogenic potential of CuO nanoparticles compared to bulk CuO and ionic copper
      in mussels Mytilus galloprovincialis.
AB  - The aim of this work was to study short-term effects on antioxidant enzyme
      activities and long-term genotoxic and carcinogenic potential of CuO
      nanoparticles (NPs) in comparison to bulk CuO and ionic copper in mussels Mytilus
      galloprovincialis after 21 days exposure to 10 MUg Cu L(-1). Then, mussels were
      kept for up to 122 days in clean water. Cu accumulation depended on the form of
      the metal and on the exposure time. CuO NPs were localized in lysosomes of
      digestive cells, as confirmed by TEM and X ray microanalysis. CuO NPs, bulk CuO
      and ionic copper produced different effects on antioxidant enzyme activities in
      digestive glands, overall increasing antioxidant activities. CuO NPs
      significantly induced catalase and superoxide dismutase activities. Fewer effects
      were observed in gills. Micronuclei frequency increased significantly in mussels
      exposed to CuO NPs and one organism treated with CuO NPs showed disseminated
      neoplasia. However, transcription levels of cancer-related genes did not vary
      significantly. Thus, short-term exposure to CuO NPs provoked oxidative stress and
      genotoxicity, but further studies are needed to determine whether these early
      events can lead to cancer development in mussels. 

PMID- 26297044
TI  - Randomized controlled trials and neuro-oncology: should alternative designs be
      considered?
AB  - Deficiencies in design and reporting of randomized controlled trials (RCTs)
      hinders interpretability and critical appraisal. The reporting quality of recent
      RCTs in neuro-oncology was analyzed to assess adequacy of design and reporting.
      The MEDLINE and EMBASE databases were searched to identify non-surgical RCTs
      (years 2005-2014, inclusive). The CONSORT and Jadad scales were used to assess
      the quality of design/reporting. Studies published in 2005-2010 were compared as
      a cohort against studies published in 2011-2014, in terms of general
      characteristics and reporting quality. A PRECIS-based scale was used to designate
      studies on the pragmatic-explanatory continuum. Spearman's test was used to
      assess correlations. Regression analysis was used to assess associations. Overall
      68 RCTs were identified. Studies were often chemotherapy-based (n = 41 studies)
      focusing upon high grade gliomas (46 %) and metastases (41 %) as the top
      pathologies. Multi-center trials (71 %) were frequent. The overall median CONSORT
      and Jadad scores were 34.5 (maximum 44) and 2 (maximum 5), respectively; these
      scores were similar in radiation and chemotherapy-based trials. Major areas of
      deficiency pertained to allocation concealment, implementation of methods, and
      blinding whereby less than 20 % of articles fulfilled all criteria. Description
      of intervention, random sequence generation, and the details regarding
      recruitment were also deficient; less than 50 % of studies fulfilled all
      criteria. Description of sample size calculations and blinding improved in later
      published cohorts. Journal impact factor was significantly associated with higher
      quality (p = 0.04). Large academic consortia, multi-center designs, ITT analysis,
      collaboration with biostatisticians, larger sample sizes, and studies with
      pragmatic objectives were more likely to achieve positive primary outcomes on
      univariate analysis; none of these variables were significant on multivariate
      analysis. Deficiencies in the quality of design/reporting of RCTs in neuro
      oncology persist. Quality improvement is necessary. Consideration of alternative
      strategies should be considered. 

PMID- 26297045
TI  - Reactive oxygen species production has a critical role in hypoxia-induced Stat3
      activation and angiogenesis in human glioblastoma.
AB  - Glioblastoma is the most aggressive primary brain tumor with hypoxia-associated
      morphologic features including pseudopalisading necrosis and endothelial
      hyperplasia. It has been known that hypoxia can activate signal transducer and
      activator of transcription 3 (Stat3) and subsequently induce angiogenesis.
      However, the molecular mechanism underlying hypoxia-induced Stat3 activation has
      not been defined. In this study, we explored the possible implication of reactive
      oxygen species (ROS) in hypoxia-driven Stat3 activation in human glioblastoma. We
      found that hypoxic stress increased ROS production as well as Stat3 activation
      and that ROS inhibitors (diphenyleneiodonium, rotenone and myxothiazol) and an
      antioxidant (N-acetyl-L-cysteine) blocked Stat3 activation under hypoxic
      conditions. To determine a major route of ROS production, we tested whether
      nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) is involved in
      hypoxia-induced ROS production. Nox4 expression was found to be increased at both
      mRNA and protein levels in hypoxic glioblastoma cells. In addition, siRNA
      mediated knockdown of Nox4 expression abolished hypoxia induced Stat3 activation
      and vascular endothelial growth factor expression, which is associated with tumor
      cells' ability to trigger tube formation of endothelial cells in vitro. Our
      findings indicate that elevated ROS production plays a crucial role for Stat3
      activation and angiogenesis in hypoxic glioblastoma cells. 

PMID- 26297046
TI  - Specific inhibition of mTOR pathway induces anti-proliferative effect and
      decreases the hormone secretion in cultured pituitary adenoma cells.
AB  - There are some evidences that pituitary tumors may be sensitive to the anti
      proliferative effects of mammalian target of rapamycin (mTOR) inhibitors, while
      the mechanism and effects remains unclear, it is necessary to find if a specific
      mTOR inhibition, including the blocking of both mTOR function and expression,
      generate any effects on pituitary adenoma cells. The object of this study was to
      examine if specific inhibition of mTOR induced anti-proliferative effect and
      decreased the GH and PRL hormones secretion in GH3 and MtT/E pituitary adenoma
      cells by using a kind of mTOR shRNA lentiviral vector. The in vitro experiments
      results showed mTOR shRNA transfection robustly reduced the GH3 and MtT/E cells
      viability in all durations (1-6 days) we performed, also specifically decreased
      both GH and PRL hormones external secretion in GH3 cells. Further results
      suggested that specific inhibition of mTOR decreased the hormones secretion
      through anti-proliferation effects on GH3 cells and reducing the hormones
      synthesis, but not through affecting the process of hormones secretion. Then we
      used phosphatidic acid (PA), a kind of mTOR activator, to promote the cell
      proliferation and GH and PRL hormones secretion in GH3 cells while the effects
      were blocked by mTOR shRNA transfection. In addition, we examined in vitro
      effects of PA treatment and mTOR shRNA gene transfection on major proteins
      expressed in the mTOR pathway in GH3 cells, and confirmed that PA treatment
      significant increased the protein levels of pmTOR, pS6 K and p4EBP1 in the
      scramble shRNA group, while the increase of protein levels was blocked by mTOR
      shRNA gene transfection. Moreover, mTOR shRNA gene transfection definitely
      inhibited the expression of mTOR and reduced the expression of pmTOR, pS6K and
      p4EBP1 in either PA or no PA treatment groups. These findings indicated that
      specific inhibition of mTOR pathway induced anti-proliferative effect and
      decreased the GH and PRL hormones secretion in cultured pituitary adenoma cells,
      which may be a novel promising and potential treatment modality for patients with
      secreting or non-secreting pituitary adenomas.

PMID- 26297047
TI  - Permissivity of the biphenyl-specific aerobic bacterial metabolic pathway towards
      analogues with various steric requirements.
AB  - It has repeatedly been shown that aryl-hydroxylating dioxygenases do not possess
      a very high substrate specificity. To gain more insight into this phenomenon, we
      examined two powerful biphenyl dioxygenases, the well-known wild-type enzyme from
      Burkholderia xenovorans LB400 (BphA-LB400) and a hybrid enzyme, based on a
      dioxygenase from Pseudomonas sp. B4-Magdeburg (BphA-B4h), for their abilities to
      dioxygenate a selection of eight biphenyl analogues in which the second aromatic
      ring was replaced by aliphatic as well as aliphatic/aromatic moieties, reflecting
      a variety of steric requirements. Interestingly, both enzymes were able to
      catalyse transformation of almost all of these compounds. While the products
      formed were identical, major differences were observed in transformation rates.
      In most cases, BphA-B4h proved to be a significantly more powerful catalyst than
      BphA-LB400. NMR characterization of the reaction products showed that the
      metabolite obtained from biphenylene underwent angular dioxygenation, whereas all
      other compounds were subject to lateral dioxygenation at ortho and meta carbons.
      Subsequent growth studies revealed that both dioxygenase source strains were able
      to utilize several of the biphenyl analogues as sole sources of carbon and
      energy. Therefore, prototype BphBCD enzymes of the biphenyl degradative pathway
      were examined for their ability to further catabolize the lateral dioxygenation
      products. All of the ortho- and meta-hydroxylated compounds were converted to
      acids, showing that this pathway is quite permissive, enabling catalysis of the
      turnover of a fairly wide variety of metabolites. 

PMID- 26297048
TI  - Severe intravenous immunoglobulin-induced hemolysis with pigment nephropathy
      managed with red cell exchange.
AB  - We report on the use of red cell exchange in a case of severe intravenous immune
      globulin induced hemolysis and pigment nephropathy. Renal impairment and
      hemoglobinuria were not ameliorated by supportive measures including hydration.
      Partial red cell exchange with group O blood reduced hemoglobinuria and appeared
      to stabilize renal function. This is the first report on the use of red cell
      exchange in this clinical setting. J. Clin. Apheresis 31:464-466, 2016. (c) 2015
      Wiley Periodicals, Inc. 

PMID- 26297049
TI  - Coding-noncoding gene expression in intrahepatic cholangiocarcinoma.
AB  - Recent studies have shown that long noncoding RNAs (lncRNAs) play crucial roles
      in human cancers. However, the function of lncRNAs and their downstream
      mechanisms are largely unknown in the molecular pathogenesis of intrahepatic
      cholangiocarcinoma (ICC). In the present study, we performed transcriptomic
      profiling of ICC and paired adjacent noncancerous tissues (N) by using lncRNA and
      messenger RNA (mRNA) microarrays. Quantitative real-time polymerase chain
      reaction was used to validate the microarray results. We tested for correlations
      between the expression levels of lncRNAs and target genes. Clinicopathologic
      characteristics and overall survival were compared using the t test and the
      Kaplan-Meier method, respectively. A total of 2773 lncRNAs were significantly
      upregulated in ICC tissues compared with the noncancerous tissues, whereas 2392
      lncRNAs were downregulated. Bioinformatic analysis indicated that most of the
      genes were involved in carcinogenesis, hepatic system diseases, and signal
      transductions. Positive correlations were found between 4 lncRNA-mRNA pairs
      (RNA43085 and SULF1, RNA47504 and KDM8, RNA58630 and PCSK6, and RNA40057 and
      CYP2D6). When the clinicopathologic characteristics were accounted for, the
      cumulative overall survival rate was found to be associated with low expression
      levels of CYP2D6 (P = 0.005) and PCSK6 (P = 0.038). Patients with high expression
      levels of CYP2D6 and RNA40057 had a better prognosis (P = 0.014). Our results
      suggested that the lncRNA expression profiling in ICC tissues is profoundly
      different from that in noncancerous tissues. Thus, lncRNA may be a potential
      diagnostic and prognostic biomarker for ICC. Furthermore, the combined assessment
      of lncRNA and mRNA expressions might predict the survival of patients with ICC. 

PMID- 26297051
TI  - Stiffness-Independent Highly Efficient On-Chip Extraction of Cell-Laden Hydrogel
      Microcapsules from Oil Emulsion into Aqueous Solution by Dielectrophoresis.
AB  - A dielectrophoresis (DEP)-based method achieves highly efficient on-chip
      extraction of cell-laden microcapsules of any stiffness from oil into aqueous
      solution. The hydrogel microcapsules can be extracted into the aqueous solution
      by DEP and interfacial tension forces with no trapped oil, while the encapsulated
      cells are free from electrical damage due to the Faraday cage effect. 

PMID- 26297050
TI  - Therapeutic targeting of inflammation and tryptophan metabolism in colon and
      gastrointestinal cancer.
AB  - Colorectal cancer (CRC) is the third most common cancer worldwide and the second
      leading cause of cancer death in the United States. Cytotoxic therapies cause
      significant adverse effects for most patients and do not offer cure in many
      advanced cases of CRC. Immunotherapy is a promising new approach to harness the
      body's own immune system and inflammatory response to attack and clear the
      cancer. Tryptophan metabolism along the kynurenine pathway (KP) is a particularly
      promising target for immunotherapy. Indoleamine 2,3-dioxygenase 1 (IDO1) is the
      most well studied of the enzymes that initiate this pathway and it is commonly
      overexpressed in CRC. Herein, we provide an in-depth review of how tryptophan
      metabolism and KP metabolites shape factors important to CRC pathogenesis
      including the host mucosal immune system, pivotal transcriptional pathways of
      neoplastic growth, and luminal microbiota. This pathway's role in other
      gastrointestinal (GI) malignancies such as gastric, pancreatic, esophageal, and
      GI stromal tumors is also discussed. Finally, we highlight how currently
      available small molecule inhibitors and emerging methods for therapeutic
      targeting of IDO1 might be applied to colon, rectal, and colitis-associated
      cancer.

PMID- 26297053
TI  - Vitamin D inhibits the growth of and virulence factor gene expression by
      Porphyromonas gingivalis and blocks activation of the nuclear factor kappa B
      transcription factor in monocytes.
AB  - BACKGROUND AND OBJECTIVE: Increasing evidence suggests that 1,25-dihydroxyvitamin
      D3 (1,25(OH)2 D3 ), a fat-soluble secosteroid hormone, has a positive impact on
      periodontal health through diverse mechanisms. The present study was aimed at
      investigating the effect of 1,25(OH)2 D3 on the growth of and virulence factor
      gene expression by the periodontopathogenic bacterium Porphyromonas gingivalis.
      The effect of 1,25(OH)2 D3 on P. gingivalis-mediated activation of nuclear factor
      kappa B (NF-kappaB) transcription factor in monocytes was also assessed. MATERIAL
      AND METHODS: A broth microdilution assay was used to determine the antibacterial
      activity of 1,25(OH)2 D3 . The modulation of virulence factor gene expression in
      P. gingivalis was assessed by quantitative reverse transcription-polymerase chain
      reaction. NF-kappaB activation was assessed using a human monocytic cell line
      stably transfected with a luciferase reporter containing NF-kappaB binding sites.
      RESULTS: Minimal inhibitory concentrations of 1,25(OH)2 D3 against P. gingivalis
      ranged from 3.125 to 6.25 MUg/mL. Moreover, a partial synergistic effect was
      observed when 1,25(OH)2 D3 was used in association with metronidazole. 1,25(OH)2
      D3 attenuated the virulence of P. gingivalis by reducing the expression of genes
      coding for important virulence factors, including adhesins (fimA, hagA and hagB)
      and proteinases (rgpA, rgpB and kgp). 1,25(OH)2 D3 dose-dependently prevented P.
      gingivalis-induced NF-kappaB activation in a monocyte model. CONCLUSION: Our
      study suggested that 1,25(OH)2 D3 selectively inhibits the growth of and
      virulence factor gene expression by P. gingivalis, in addition to attenuating NF
      kappaB activation by this periodontopathogen. This dual action on P. gingivalis
      and the inflammatory response of host cells may be of particular interest with a
      view to developing a novel and inexpensive preventive/therapeutic strategy.

PMID- 26297054
TI  - The impact of fellowships on surgical resident training in a multispecialty
      cohort in Australia and New Zealand.
AB  - INTRODUCTION: Fellowships in surgery are increasing in number, and concerns have
      been raised regarding their impact on resident training. Although fellows may
      contribute to resident education and training, they also compete for operative
      and other experience. This study aimed to quantify the impact of fellowships on
      resident training in a binational multispecialty cohort. METHODS: The operative
      case volumes and primary operator rates of surgery trainees (residents) in
      Australia and New Zealand were compared between units with and without fellows.
      Trainees also were surveyed using Likert Scales to assess quality of operative
      and other experience in units with and without fellows. RESULTS: Data from 911
      trainees over 2 terms was analyzed; survey response rate 42%. Of all trainees,
      42% worked with fellows. Trainees in units without fellows were involved in more
      major (P = .03) and minor (P < .0001) cases. Primary operator rates were
      comparable, but trainees in units without fellows were less often assistants,
      reported an increased quality of elective operating experience, and reported more
      favorable completion of learning objectives (all P < .05). These findings were
      consistent between tertiary and nontertiary hospitals. Thematic analysis showed
      positive benefits of fellows in teaching, training and mentorship, but negative
      impacts on case exposure, competition for operating, and clinical experience.
      CONCLUSION: Fellows may assist in the teaching and training of residents, but
      residents working with fellows experience a decreased quantity of operative
      experience that may impact several aspects of the quality of training. Surgical
      educators must actively balance the learning needs of fellows and residents.

PMID- 26297052
TI  - Determination of cell uptake pathways for tumor inhibitor lysyl oxidase
      propeptide.
AB  - The lysyl oxidase propeptide (LOX-PP) is derived from pro-lysyl oxidase (Pro-LOX)
      by extracellular biosynthetic proteolysis. LOX-PP inhibits breast and prostate
      cancer xenograft tumor growth and has tumor suppressor activity. Although,
      several intracellular targets and molecular mechanisms of action of LOX-PP have
      been identified, LOX-PP uptake pathways have not been reported. Here we
      demonstrate that the major uptake pathway for recombinant LOX-PP (rLOX-PP) is
      PI3K-dependent macropinocytosis in PWR-1E, PC3, SCC9, MDA-MB-231 cell lines. A
      secondary pathway appears to be dynamin- and caveola dependent. The ionic
      properties of highly basic rLOX-PP provide buffering capacity at both high and
      low pHs. We suggest that the buffering capacity of rLOX-PP, which serves to limit
      endosomal acidification, sustains PI3K-dependent macropinocytosis in endosomes
      which in turn is likely to facilitate LOX-PP endosomal escape into the cytoplasm
      and its observed interactions with cytoplasmic targets and nuclear uptake. 

PMID- 26297055
TI  - A prospective randomized controlled trial of laparoscopic repair versus open
      repair for perforated peptic ulcers.
AB  - BACKGROUND: Although laparoscopic repair (LR) of perforated peptic ulcers (PPUs)
      has long been accepted, clinical evidence comparing LR versus open repair (OR)
      remains lacking. Consequently, this study compared the clinical outcomes and cost
      effectiveness of LR versus OR. METHODS: From January 2010 to June 2014, 119
      patients with PPU were divided randomly into LR (58 patients) and OR (61
      patients) groups that were comparable in age, sex, smoking and drinking history,
      symptom duration, comorbidity, American Society of Anesthesiologists grade, Boey
      score, and white blood cell count. RESULTS: The operative times for LR versus OR
      did not differ greatly (70 [interquartile range 60-90] vs 75 [60-90] minutes,
      respectively, P = .692), nor did postoperative complications. The LR group,
      however, required substantially less fentanyl than the OR group (0.74 +/- 0.33 mg
      vs 1.04 +/- 0.39 mg, P < .001). Moreover, the duration of hospital stay for the
      LR group was much shorter than those of the OR group (7 [5-9] vs 8 [7-10] days,
      respectively, P < .001). Although total hospital costs were similar (P = .465),
      the median intraoperative costs were greater for LR than for OR patients, at
      Y6772 and Y5626, respectively (P < .001). The median cost of ward stay tended to
      be Y865 less in the LR group but was not statistically relevant. CONCLUSION: LR
      and conventional OR are comparable in terms of operative duration and
      complications. The obvious advantage of LR is the greatly decreased hospital stay
      and less postoperative pain, at similar total hospital costs. Therefore, LR may
      be preferable for treating PPU in selected patients.

PMID- 26297057
TI  - Impact of obesity on postoperative outcome of hepatic resection for colorectal
      metastases.
AB  - BACKGROUND: Outcomes in obese patients who underwent liver resection have been
      analyzed, but series are heterogeneous and data are controversial. The aim of
      this study was to analyze short-outcome in obese patients undergone hepatectomy
      for colorectal metastases. STUDY DESIGN: A retrospective analysis on 1,021
      consecutive hepatectomies between January 2000 and April 2014 for colorectal
      metastases was carried out. World Health Organization Classification of obesity
      (body mass index >30 kg/m(2)) was used to identify 140 obese patients. Outcomes
      were compared among obese and nonobese patients. RESULTS: Obese patients were
      mainly male (78%) and were associated more frequently with hypertension (51% vs
      29%, P < .001), ischemic heart disease (9% vs 3%, P = .007), and diabetes (23% vs
      10%, P < .001) compared with nonobese patients. Approximately 30% of patients
      underwent major hepatectomy in the 2 groups. Associated resections were performed
      in 36% of obese and 37% of nonobese patients. Median parenchymal transection time
      (80 +/- 64 minutes vs 70 +/- 50 minutes, P = .013) and blood loss (300 +/- 420 vs
      200 +/- 282, P = .001) were greater in obese patients. Postoperative mortality
      was nil in obese patients and 0.6% in nonobese patients. Overall morbidity was
      greater in obese patients (41% vs 31%, P = .012) mainly related to pulmonary
      complications (16% vs 9%, P = .012). Reinterventions were more frequent in obese
      patients (3.6% vs 1.2%, P = .004). Median hospital stay was comparable. At
      pathologic examination, hepatic steatosis was greater in obese (69% vs 43%, P <
      .001). At multivariate analysis, age >65 years (odds ratio [OR] 1.43, 95%
      confidence interval [95% CI] 1.09-1.88), obesity (OR 1.64, 95% CI 1.13-2.38),
      major hepatectomies (OR 1.65, 95% CI 1.31-2.33), and associated resections (OR
      1.67, I95% CI 1.27-2.20) were independent predictors of overall morbidity (P <
      .001). Among obese patients, there was a positive correlation between age and
      severity of complications (R = 0.173, P = .041). CONCLUSION: Obese patients
      undergoing hepatectomy for colorectal metastases should be approached with
      caution because of an increased risk of postoperative morbidity.

PMID- 26297056
TI  - E-cadherin expression in obesity-associated, Kras-initiated pancreatic ductal
      adenocarcinoma in mice.
AB  - BACKGROUND: The epithelial-mesenchymal transition (EMT) is critical in the
      development of invasive epithelial malignancies. EMT is accelerated by
      inflammation and results in decreased E-cadherin expression. Diet-induced obesity
      is an inflammatory state that accelerates pancreatic carcinogenesis; its effect
      on EMT and E-cadherin expression in the development of pancreatic ductal
      adenocarcinoma is unclear. METHODS: Conditional Kras(G12D) mice were fed a
      control diet or a high-fat, high-calorie diet for 3 or 9 months (n = 10 each).
      Immunohistochemistry with anti-E-cadherin antibody was performed. E-cadherin
      expression was characterized by staining intensity, location, and proportion of
      positive cells. In vitro expression of E-cadherin and Slug in primary pancreatic
      intraepithelial neoplasia (PanIN) and cancer cells was determined by Western
      blot. RESULTS: The HFCD led to increased weight gain in both 3- (15.8 vs 5.6 g, P
      < .001) and 9-month (19.8 vs 12.9 g, P = .007) mice. No differences in E-cadherin
      expression among various stages of preinvasive PanIN lesions were found-
      regardless of age or diet. In invasive cancer, E-cadherin expression was
      aberrant, with loss of membranous staining and prominent cytoplasmic staining,
      associated with strong, cytoplasmic expression of beta-catenin. In vitro
      expression of E-cadherin was greatest in primary PanIN cells, accompanied by
      absent Slug expression. Cancer cell lines demonstrated significantly decreased E
      cadherin expression in the presence of upregulated Slug. CONCLUSION: Despite
      increased pancreatic inflammation and accelerated carcinogenesis, the high-fat,
      high-calorie diet did not induce changes in E-cadherin expression in PanIN
      lesions of all stages. Invasive lesions demonstrated aberrant cytoplasmic E
      cadherin staining. Loss of normal membranous localization may reflect a
      functional loss of E-cadherin.

PMID- 26297059
TI  - Diagnostically Challenging Epithelioid Soft Tissue Tumors.
AB  - In this article, we focus on the histologic features, differential diagnosis, and
      potential pitfalls in the diagnosis of epithelioid sarcoma, alveolar soft part
      sarcoma, clear-cell sarcoma, ossifying fibromyxoid tumor, and malignant
      extrarenal rhabdoid tumor. Numerous other soft tissue tumors also may have
      epithelioid variants or epithelioid features. Examples include epithelioid
      angiosarcoma, epithelioid malignant peripheral nerve sheath tumor, epithelioid
      gastrointestinal stromal tumor, and perivascular epithelioid cell tumor, among
      others. 

PMID- 26297058
TI  - A clinical pharmacokinetic microdosing study of docetaxel with Japanese patients
      with cancer.
AB  - PURPOSE: Whether microdosing studies can be used to evaluate the human
      pharmacokinetics of new anticancer drugs remains unclear. The disposition of
      docetaxel in cancer patients is linear in terms of dose proportionality. We
      examined whether the pharmacokinetics of docetaxel in a clinically relevant
      therapeutic dose could be predicted from the pharmacokinetics of a microdose of
      docetaxel in Japanese patients with cancer. METHODS: A microdose of docetaxel
      (100 MUg/patient) was given by 5-min intravenous infusion on day 1, followed by a
      therapeutic dose of docetaxel (60-75 mg m(-2)), given by 1-h intravenous infusion
      on day 8. Plasma docetaxel was analyzed by liquid chromatography-tandem mass
      spectrometry. A two-compartment pharmacokinetic model was used to calculate the
      area under the plasma concentration-time curve from time 0 to infinity (AUC0
      inf). RESULTS: Nine patients received both a microdose and therapeutic dose of
      docetaxel. The AUC0-inf after microdosing was 3640 +/- 1150 ng h L(-1), while
      that after therapeutic dosing adjusted to 100 mg/patient was 2230 +/- 757 ug h L(
      1). The ratio of docetaxel clearance in therapeutic dose to that in microdose was
      1.8 (P = 0.0041). Plasma alpha1-acid glycoprotein concentrations negatively
      correlated with docetaxel clearance at therapeutic dose, whereas the trend was
      weak at microdose. CONCLUSION: Docetaxel clearance showed marginal nonlinearity
      between microdose and therapeutic dose, presumably because of saturation of
      plasma protein binding; however, the magnitude was within twofold, allowing
      practically acceptable extrapolation.

PMID- 26297060
TI  - Diagnostically Challenging Epithelioid Vascular Tumors.
AB  - The diagnosis of vascular tumors is a challenging area in soft tissue pathology.
      Epithelioid vascular tumors pose a particular challenge. Due to the epithelioid
      morphology of the tumor cells, they can be misdiagnosed as a variety of other
      entities, including metastatic carcinoma or epithelioid sarcoma. Furthermore, it
      can be difficult to distinguish between different epithelioid vascular tumors.
      This review focuses on vascular tumors characterized by epithelioid endothelial
      cells, including epithelioid hemangioma, cutaneous epithelioid angiomatous
      nodule, epithelioid hemangioendothelioma, epithelioid sarcomalike
      hemangioendothelioma/pseudomyogenic hemangioendothelioma, and epithelioid
      angiosarcoma. 

PMID- 26297061
TI  - Diagnostically Challenging Spindle Cell Neoplasms of the Retroperitoneum.
AB  - The diagnostic spectrum of spindle cell neoplasms arising in the retroperitoneum
      is wide and, in the presence of commonly shared morphologic features, it may be
      challenging to establish a correct diagnosis in certain cases. Beyond seemingly
      undifferentiated spindle cell morphology, most neoplasms may reveal distinctive
      adipocytic, smooth muscle or myofibroblastic or nerve sheath differentiation and
      show additional diagnostic clues or characteristic molecular abnormalities.
      Obtaining sufficient and representative biopsy material, a thorough work-up, and
      extensive sampling of gross specimens followed by a combined histopathologic,
      immunohistochemical, and, if necessary, molecular work-up of these cases is
      advisable so as not to miss important diagnostic and/or prognostic indicators.

PMID- 26297062
TI  - Diagnostically Challenging "Fatty" Retroperitoneal Tumors.
AB  - A variety of benign and malignant retroperitoneal mesenchymal lesions may have a
      component of adipose tissue, including entities such as lipoma, myolipoma,
      angiomyolipoma, solitary fibrous tumor, genital stromal tumors, and well
      differentiated/dedifferentiated liposarcoma. Although definitive diagnosis is
      usually straightforward on the complete resection specimen, it is often more
      difficult to workup these lesions on small biopsy samples. This review focuses on
      challenging diagnostic scenarios of retroperitoneal lesions with a "fatty"
      component and provides major differential diagnoses for commonly encountered
      morphologic patterns, clinicopathologic features of the various entities, and
      strategy for use of ancillary techniques, such as immunohistochemistry and
      cytogenetic studies. 

PMID- 26297063
TI  - Selected Diagnostically Challenging Pediatric Soft Tissue Tumors.
AB  - Many benign and malignant soft tissue tumors in children are challenging and
      their diagnosis requires knowledge of their vast diversity, histopathological
      complexity, and immunohistochemical, cytogenetic, and molecular characteristics.
      The importance of clinical and imaging features cannot be overstated. Soft tissue
      sarcomas account for 15% of all pediatric malignancies after leukemia/lymphoma,
      central nervous system tumors, neuroblastoma and Wilms tumor. This article
      discusses selected challenging pediatric soft tissue tumors with an update on
      recently described entities. 

PMID- 26297064
TI  - Chondro-Osseous Lesions of Soft Tissue.
AB  - Soft tissue lesions can contain bone or cartilage matrix as an incidental, often
      metaplastic, phenomenon or as a diagnostic feature. The latter category includes
      a diverse group ranging from self-limited proliferations to benign neoplasms to
      aggressive malignancies. Correlating imaging findings with pathology is mandatory
      to confirm that a tumor producing bone or cartilage, in fact, originates from
      soft tissue rather than from the skeleton. The distinction can have dramatic
      diagnostic and therapeutic implications. This content focuses on the gross,
      histologic, radiographic, and clinical features of bone or cartilage-producing
      soft tissue lesions. Recent discoveries regarding tumor-specific genetics are
      discussed. 

PMID- 26297065
TI  - Myoepithelial Tumors: An Update.
AB  - Primary myoepithelial neoplasms of soft tissue are uncommon, and have been
      increasingly characterized by clinicopathologic and genetic means. Tumors are
      classified as mixed tumor/chondroid syringoma, myoepithelioma, and myoepithelial
      carcinoma, and they share morphologic, immunophenotypic, and genetic features
      with their salivary gland counterparts. However, soft tissue myoepithelial tumors
      are classified as malignant based on the presence of cytologic atypia, in
      contrast to the criterion of invasive growth in salivary gland sites. This review
      discusses the clinicopathologic and morphologic characteristics, distinct
      variants, and currently known genetic alterations of myoepithelial neoplasms of
      soft tissue, skin, and bone. 

PMID- 26297066
TI  - The New Kids on the Block: Recently Characterized Soft Tissue Tumors.
AB  - Soft tissue pathology is a rapidly changing subspecialty. New entities are
      described relatively often, and new molecular findings for soft tissue tumors are
      reported in the literature almost every month. This article summarizes the major
      features and diagnostic approach to several recently characterized entities:
      superficial CD34-positive fibroblastic tumor, fibrosarcoma-like lipomatous
      neoplasm, angiofibroma of soft tissue, low-grade sinonasal sarcoma with neural
      and myogenic features, malignant gastrointestinal neuroectodermal tumor,
      hemosiderotic fibrolipomatous tumor, and epithelioid inflammatory myofibroblastic
      sarcoma. Additionally, the article also provides a summary table of recent
      molecular findings in soft tissue tumors. 

PMID- 26297067
TI  - Non-mesenchymal Mimics of Sarcoma.
AB  - A variety of different non-mesenchymal neoplasms may mimic sarcoma, in particular
      sarcomatoid carcinoma and melanoma, but also mesothelioma and rarely some
      lymphomas. This article reviews the key clinical and histologic features of such
      neoplasms in different settings, along with the use of ancillary studies to help
      identify the tumor types most frequently misdiagnosed as sarcoma. 

PMID- 26297068
TI  - Genetics of Gastrointestinal Stromal Tumors: A Heterogeneous Family of Tumors?
AB  - Approximately 85-90% of adult gastrointestinal stromal tumors (GISTs) harbor KIT
      and PDGFRA mutations. The remaining cases, including the majority of pediatric
      GISTs, lack these mutations, and have been designated as KIT/PDGFRA wild-type
      (WT) GISTs. Nearly 15% of WT GISTs harbor BRAF mutations, while others arise in
      patients with type I neurofibromatosis. Recent work has confirmed that 20-40% of
      KIT/PDGFRA WT GISTs show loss of function of succinate dehydrogenase complex.
      Less than 5% of GISTs lack known molecular alterations ("quadruple-negative"
      GISTs). Thus, it is important to consider genotyping these tumors to help better
      define their clinical behavior and therapy. 

PMID- 26297070
TI  - Diagnostic Challenges and Recent Developments in Soft Tissue Pathology. Preface.

PMID- 26297069
TI  - Advances in the Molecular Analysis of Soft Tissue Tumors and Clinical
      Implications.
AB  - The emergence of high-throughput molecular technologies has accelerated the
      discovery of novel diagnostic, prognostic and predictive molecular markers.
      Clinical implementation of these technologies is expected to transform the
      practice of surgical pathology. In soft tissue tumor pathology, accurate
      interpretation of comprehensive genomic data provides useful diagnostic and
      prognostic information, and informs therapeutic decisions. This article reviews
      recently developed molecular technologies, focusing on their application to the
      study of soft tissue tumors. Emphasis is made on practical issues relevant to the
      surgical pathologist. The concept of genomically-informed therapies is presented
      as an essential motivation to identify targetable molecular alterations in
      sarcoma. 

PMID- 26297071
TI  - The progress in understanding and treatment of diabetic retinopathy.
AB  - Diabetic retinopathy is the most frequently occurring complication of diabetes
      mellitus and remains a leading cause of vision loss globally. Its aetiology and
      pathology have been extensively studied for half a century, yet there are
      disappointingly few therapeutic options. Although some new treatments have been
      introduced for diabetic macular oedema (DMO) (e.g. intravitreal vascular
      endothelial growth factor inhibitors ('anti-VEGFs') and new steroids), up to 50%
      of patients fail to respond. Furthermore, for people with proliferative diabetic
      retinopathy (PDR), laser photocoagulation remains a mainstay therapy, even though
      it is an inherently destructive procedure. This review summarises the clinical
      features of diabetic retinopathy and its risk factors. It describes details of
      retinal pathology and how advances in our understanding of pathogenesis have led
      to identification of new therapeutic targets. We emphasise that although there
      have been significant advances, there is still a pressing need for a better
      understanding basic mechanisms enable development of reliable and robust means to
      identify patients at highest risk, and to intervene effectively before vision
      loss occurs. 

PMID- 26297072
TI  - Guidelines update: Post-treatment follow-up of adult head and neck squamous cell
      carcinoma: Screening for metastasis and metachronous esophageal and bronchial
      locations.
AB  - OBJECTIVE: The present article is an update of the guideline of the French
      Society of Otorhinolaryngology and Head and Neck Surgery (SFORL) on the post
      treatment follow-up of adult head and neck squamous cell carcinoma concerning
      screening for metastasis and metachronous esophageal and bronchial locations.
      METHODS: A multidisciplinary work-group was entrusted with a review of the
      literature on the above topic. Guidelines were drawn up, based on the articles
      retrieved and the work-group members' own experience. These were then reviewed by
      an editorial group independent of the work-group. A coordination meeting then
      finalized the guidelines. Guidelines were graded A, B, C or "expert opinion"
      according to decreasing level of evidence.

PMID- 26297073
TI  - Guidelines of the French Society of Otorhinolaryngology (SFORL), short version.
      Diagnosis of local recurrence and metachronous locations in head and neck
      oncology.
AB  - Surveillance is fundamental to the management of head and neck cancer. The
      present guidelines of the French ENT society (SFORL) were drawn up by a group of
      experts in the field, and are intended to specify the modalities of management,
      based on a review of the literature and, where data are lacking, to provide
      expert opinion. The present paper deals with guidelines for the diagnosis of
      local and regional recurrence and metachronous head and neck locations.
      Locoregional recurrence usually occurs within 3 years of primary treatment and is
      mainly related to the characteristics of the primary tumor and the treatment
      measures taken. Laryngeal location, safe primary resection margins, low level of
      lymph node invasion, unimodal primary treatment and early diagnosis of recurrence
      are factors of good prognosis. Systematic imaging surveillance may be considered
      for patients for whom a curative technique exists and when surveillance is
      difficult. The role of PET-scanning remains to be determined. Metachronous
      locations are frequent, even in the late course; prolonged surveillance is
      appropriate. The best preventive measure is cessation of alcohol abuse and
      smoking. Patient education is primordial.

PMID- 26297074
TI  - Exotic grasses and nitrate enrichment alter soil carbon cycling along an urban
      rural tropical forest gradient.
AB  - Urban areas are expanding rapidly in tropical regions, with potential to alter
      ecosystem dynamics. In particular, exotic grasses and atmospheric nitrogen (N)
      deposition simultaneously affect tropical urbanized landscapes, with unknown
      effects on properties like soil carbon (C) storage. We hypothesized that (H1)
      soil nitrate (NO3 (-) ) is elevated nearer to the urban core, reflecting N
      deposition gradients. (H2) Exotic grasslands have elevated soil NO3 (-) and
      decreased soil C relative to secondary forests, with higher N promoting
      decomposer activity. (H3) Exotic grasslands have greater seasonality in soil NO3
      (-) vs. secondary forests, due to higher sensitivity of grassland soil moisture
      to rainfall. We predicted that NO3 (-) would be positively related to dissolved
      organic C (DOC) production via changes in decomposer activity. We measured six
      paired grassland/secondary forest sites along a tropical urban-to-rural gradient
      during the three dominant seasons (hurricane, dry, and early wet). We found that
      (1) soil NO3 (-) was generally elevated nearer to the urban core, with
      particularly clear spatial trends for grasslands. (2) Exotic grasslands had lower
      soil C than secondary forests, which was related to elevated decomposer enzyme
      activities and soil respiration. Unexpectedly, soil NO3 (-) was negatively
      related to enzyme activities, and was lower in grasslands than forests. (3)
      Grasslands had greater soil NO3 (-) seasonality vs. forests, but this was not
      strongly linked to shifts in soil moisture or DOC. Our results suggest that
      exotic grasses in tropical regions are likely to drastically reduce soil C
      storage, but that N deposition may have an opposite effect via suppression of
      enzyme activities. However, soil NO3 (-) accumulation here was higher in urban
      forests than grasslands, potentially related to of aboveground N interception.
      Net urban effects on C storage across tropical landscapes will likely vary
      depending on the mosaic of grass cover, rates of N deposition, and responses by
      local decomposer communities. 

PMID- 26297075
TI  - A feasibility design study on a neutron spectrometer for BNCT with liquid
      moderator.
AB  - Neutrons generated by accelerators have various energy spectra. However, only
      limited methods are available to measure the whole neutron energy spectrum,
      especially when including the epithermal region that is normally used in BNCT. In
      the present study, we carried out the design study on a new neutron spectrometer
      that can measure such a neutron spectrum more accurately, precisely and with
      higher energy resolution, using an unfolding technique and a liquid moderator. 

PMID- 26297076
TI  - Compliance and persistence with daily, weekly, and monthly bisphosphonates for
      osteoporosis in Japan: analysis of data from the CISA.
AB  - Compliance and persistence with daily, weekly, and monthly bisphosphonates (BPs)
      for osteoporosis were assessed using data from the Platform for Clinical
      Information Statistical Analysis (CISA) database that contains data of
      prescriptions in 13 university hospitals in Japan. The analysis revealed
      compliance and persistence improved as the dosing interval increases. PURPOSE:
      BPs are an effective first-line therapy for osteoporosis, but adherence is low.
      Compliance (medication possession ratio, MPR) and persistence (time to
      discontinuation) with daily, weekly, and monthly BPs were compared to ensure
      better adherence. METHODS: Using data from the CISA database containing
      prescription data in 13 university hospitals in Japan, adherence to oral BPs of
      osteoporotic patients was investigated. Daily and weekly BPs were compared for
      compliance and persistence over 5 and 8 years, and daily, weekly, and monthly BPs
      for those over 1 and 2 years. RESULTS: MPR over 5 years was 20.8 and 60.9 % for
      daily and weekly BPs (p < 0.001), respectively. MPR over 1 year was 38.6, 70.6,
      and 77.7 % for daily, weekly, and monthly BPs (P < 0.001), respectively.
      Persistence over 8 years was significantly higher in weekly than daily BPs (p <
      0.001), and that over 5 years was highest in patients receiving BPs monthly (p <
      0.01). CONCLUSION: The present analysis indicates that a monthly regimen has
      better adherence to treatment as compared with weekly and daily regimens.

PMID- 26297077
TI  - The economic benefits of disease triggered early harvest: A case study of
      pancreas disease in farmed Atlantic salmon from Norway.
AB  - Pancreas disease (PD) is an important viral disease in Norwegian, Scottish and
      Irish aquaculture causing biological losses in terms of reduced growth,
      mortality, increased feed conversion ratio, and carcass downgrading. We developed
      a bio-economic model to investigate the economic benefits of a disease triggered
      early harvesting strategy to control PD losses. In this strategy, the salmon farm
      adopts a PCR (Polymerase Chain Reaction) diagnostic screening program to monitor
      the virus levels in stocks. Virus levels are used to forecast a clinical outbreak
      of pancreas disease, which then initiates a prescheduled harvest of the stock to
      avoid disease losses. The model is based on data inputs from national statistics,
      literature, company data, and an expert panel, and use stochastic simulations to
      account for the variation and/or uncertainty associated with disease effects and
      selected production expenditures. With the model, we compared the impacts of a
      salmon farm undergoing prescheduled harvest versus the salmon farm going through
      a PD outbreak. We also estimated the direct costs of a PD outbreak as the sum of
      biological losses, treatment costs, prevention costs, and other additional costs,
      less the costs of insurance pay-outs. Simulation results suggests that the
      economic benefit from a prescheduled harvest is positive once the average salmon
      weight at the farm has reached 3.2kg or more for an average Norwegian salmon farm
      stocked with 1,000,000smolts and using average salmon sales prices for 2013. The
      direct costs from a PD outbreak occurring nine months (average salmon weight
      1.91kg) after sea transfer and using 2013 sales prices was on average estimated
      at NOK 55.4 million (5%, 50% and 90% percentile: 38.0, 55.8 and 72.4) (NOK=?0.128
      in 2013). Sensitivity analyses revealed that the losses from a PD outbreak are
      sensitive to feed- and salmon sales prices, and that high 2013 sales prices
      contributed to substantial losses associated with a PD outbreak. 

PMID- 26297078
TI  - An Approach to Various Gastric Pathologies Using an "Image Appearance-Based
      Classification" on Computed Tomography.
AB  - Although pathologies affecting stomach are commonly encountered in computed
      tomography imaging of the abdomen, they are frequently overlooked. Their
      etiologies are often diverse; however, most of them have certain well-documented
      imaging characteristics. Conventionally the stomach abnormalities were classified
      according to their etiopathogenesis. This article aims at providing the readers
      with an easy approach by categorizing abnormalities of stomach using a novel
      image appearance-based classification. An attempt to illustrate various gastric
      pathologies using this new classification by means of pictorial examples is made.
      Basic computed tomography imaging anatomy of the stomach and imaging techniques
      that need to be adapted are also emphasized in the outset of the discussion. 

PMID- 26297079
TI  - Erratum to: Remarkable Phenytoin Sensitivity in 4 Children with SCN8A-related
      Epilepsy: A Molecular Neuropharmacological Approach.

PMID- 26297080
TI  - David Sackett 1934-2015.

PMID- 26297081
TI  - Why Did the Randomized Clinical Trial Become the Primary Focus of My Career?

PMID- 26297082
TI  - An Analysis of the Public Financial Support Eligibility Rule for French Dependent
      Elders with Alzheimer's Disease.
AB  - BACKGROUND: It is crucial to define health policies that target patients with the
      highest needs. In France, public financial support is provided to dependent
      patients: it can be used to finance informal care time and nonmedical care use.
      Eligibility for public subsidies and reimbursement of costs is associated with a
      specific tool: the autonomie gerontologie groupes iso-ressources (AGGIR) scale
      score. OBJECTIVE: Our objective was to explore whether patients with Alzheimer's
      disease who are eligible for public financial support have greater needs than do
      noneligible patients. METHODS: Using data from the Dependance des patients
      atteints de la maladie d'Alzheimer en France study, we calculated nonmedical care
      expenditures (in ?) using microcosting methods and informal care time demand
      (hours/month) using the Resource Use in Dementia questionnaire. We measured the
      burden associated with informal care provision with Zarit Burden Interview. We
      used a modified two-part model to explore the correlation between public
      financial support eligibility and these three variables. RESULTS: We find
      evidence of higher informal care use, higher informal caregivers' burden, and
      higher care expenditures when patients have an AGGIR scale score corresponding to
      public financial support eligibility. CONCLUSIONS: The AGGIR scale is useful to
      target patients with the highest costs and needs. Given our results, public
      subsidies could be used to further sustain informal caregivers networks by
      financing programs dedicated to lowering informal caregivers' burden.

PMID- 26297084
TI  - The Cost-Effectiveness of Cognitive-Behavioral Group Training for Patients with
      Unexplained Physical Symptoms.
AB  - OBJECTIVE: The aim of the study was to evaluate the cost-effectiveness of a
      cognitive-behavioral group training compared with a wait-list control for
      patients with unexplained physical symptoms (UPS). METHODS: A probabilistic
      decision-analytic Markov model was developed with three health states (poor
      health, average health, and death) based on a cutoff score of the Physical
      Component Summary of the short-form 36 health survey. To assess the cost
      effectiveness in terms of cost per quality-adjusted life-year (QALY), a societal
      perspective was adopted. The model consisted of cycles of 3 months and a time
      horizon of 4 years. Data for the model were derived from a randomized controlled
      trial, in which 162 patients with UPS were randomized either to cognitive
      behavioral group training or to the wait-list control. Data were assessed at
      baseline and after the training of 3 months or after a wait-list period of 3
      months. In addition, the training group was followed in an uncontrolled phase and
      assessed at 3 months and 1 year after the training. RESULTS: After 4 years, the
      group training was in terms of cost-effectiveness "dominant" compared with the
      wait-list control; there was a positive effect of 0.06 QALYs and a ?828 reduction
      in costs. The cost-effectiveness improved with a longer time horizon. A threshold
      of ?30,000/QALY was passed after 18 months. The group training was cost saving
      after 33 months. CONCLUSIONS: Cognitive-behavioral group training is a cost
      effective treatment compared with the wait-list control for patients with UPS.

PMID- 26297083
TI  - The Cost-Effectiveness of Different Hearing Screening Strategies for 50- to 70
      Year-Old Adults: A Markov Model.
AB  - OBJECTIVE: To assess the cost-effectiveness of screening 50- to 70-year-old
      adults for hearing loss in The Netherlands. We compared no screening, telephone
      screening, Internet screening, screening with a handheld screening device, and
      audiometric screening for various starting ages and a varying number of repeated
      screenings. METHODS: The costs per quality-adjusted life-year (QALY) for no
      screening and for 76 screening strategies were analyzed using a Markov model with
      cohort simulation for the year 2011. Screening was deemed to be cost-effective if
      the costs were less than ?20,000/QALY. RESULTS: Screening with a handheld
      screening device and audiometric screening were generally more costly but less
      effective than telephone and Internet screening. Internet screening strategies
      were slightly better than telephone screening strategies. Internet screening at
      age 50 years, repeated at ages 55, 60, 65, and 70 years, was the most cost
      effective strategy, costing ?3699/QALY. At a threshold of ?20,000/QALY, this
      strategy was with 100% certainty cost-effective compared with current practice
      and with 69% certainty the most cost-effective strategy among all strategies.
      CONCLUSIONS: This study suggests that Internet screening at age 50 years,
      repeated at ages 55, 60, 65, and 70 years, is the optimal strategy to screen for
      hearing loss and might be considered for nationwide implementation.

PMID- 26297085
TI  - Measuring Preferences for a Diabetes Pay-for-Performance for Patient (P4P4P)
      Program using a Discrete Choice Experiment.
AB  - OBJECTIVE: To elicit a patient's willingness to participate in a diabetes pay-for
      performance for patient (P4P4P) program using a discrete choice experiment
      method. METHODS: The survey was conducted in March 2013. Our sample was drawn
      from patients with diabetes at five hospitals in Taiwan (International
      Classification of Diseases, Ninth Revision, Clinical Modification code 250). The
      sample size was 838 patients. The discrete choice experiment questionnaire
      included the attributes monthly cash rewards, exercise time, diet control, and
      program duration. We estimated a bivariate probit model to derive willingness-to
      accept levels after accounting for the characteristics (e.g., severity and
      comorbidity) of patients with diabetes. RESULTS: The preferred program was a 3
      year program involving 30 minutes of exercise per day and flexible diet control.
      Offering an incentive of approximately US $67 in cash per month appears to
      increase the likelihood that patients with diabetes will participate in the
      preferred P4P4P program by approximately 50%. CONCLUSIONS: Patients with more
      disadvantageous characteristics (e.g., elderly, low income, greater comorbidity,
      and severity) could have less to gain from participating in the program and thus
      require a higher monetary incentive to compensate for the disutility caused by
      participating in the program's activities. Our result demonstrates that a modest
      financial incentive could increase the likelihood of program participation after
      accounting for the attributes of the P4P4P program and patients' characteristics.

PMID- 26297086
TI  - Cost-Effectiveness of Reduced Waiting Time for Head and Neck Cancer Patients due
      to a Lean Process Redesign.
AB  - BACKGROUND: Compared with new technologies, the redesign of care processes is
      generally considered less attractive to improve patient outcomes. Nevertheless,
      it might result in better patient outcomes, without further increasing costs.
      Because early initiation of treatment is of vital importance for patients with
      head and neck cancer (HNC), these care processes were redesigned. OBJECTIVES:
      This study aimed to assess patient outcomes and cost-effectiveness of this
      redesign. METHODS: An economic (Markov) model was constructed to evaluate the
      biopsy process of suspicious lesion under local instead of general anesthesia,
      and combining computed tomography and positron emission tomography for
      diagnostics and radiotherapy planning. Patients treated for HNC were included in
      the model stratified by disease location (larynx, oropharynx, hypopharynx, and
      oral cavity) and stage (I-II and III-IV). Probabilistic sensitivity analyses were
      performed. RESULTS: Waiting time before treatment start reduced from 5 to 22 days
      for the included patient groups, resulting in 0.13 to 0.66 additional quality
      adjusted life-years. The new workflow was cost-effective for all the included
      patient groups, using a ceiling ratio of ?80,000 or ?20,000. For patients treated
      for tumors located at the larynx and oral cavity, the new workflow resulted in
      additional quality-adjusted life-years, and costs decreased compared with the
      regular workflow. The health care payer benefited ?14.1 million and ?91.5
      million, respectively, when individual net monetary benefits were extrapolated to
      an organizational level and a national level. CONCLUSIONS: The redesigned care
      process reduced the waiting time for the treatment of patients with HNC and
      proved cost-effective. Because care improved, implementation on a wider scale
      should be considered.

PMID- 26297087
TI  - Cost-Effectiveness of Repetitive Transcranial Magnetic Stimulation versus
      Antidepressant Therapy for Treatment-Resistant Depression.
AB  - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) therapy is a
      clinically safe, noninvasive, nonsystemic treatment for major depressive
      disorder. OBJECTIVE: We evaluated the cost-effectiveness of rTMS versus
      pharmacotherapy for the treatment of patients with major depressive disorder who
      have failed at least two adequate courses of antidepressant medications. METHODS:
      A 3-year Markov microsimulation model with 2-monthly cycles was used to compare
      the costs and quality-adjusted life-years (QALYs) of rTMS and a mix of
      antidepressant medications (including selective serotonin reuptake inhibitors,
      serotonin and norepinephrine reuptake inhibitors, tricyclics, noradrenergic and
      specific serotonergic antidepressants, and monoamine oxidase inhibitors). The
      model synthesized data sourced from published literature, national cost reports,
      and expert opinions. Incremental cost-utility ratios were calculated, and
      uncertainty of the results was assessed using univariate and multivariate
      probabilistic sensitivity analyses. RESULTS: Compared with pharmacotherapy, rTMS
      is a dominant/cost-effective alternative for patients with treatment-resistant
      depressive disorder. The model predicted that QALYs gained with rTMS were higher
      than those gained with antidepressant medications (1.25 vs. 1.18 QALYs) while
      costs were slightly less (AU $31,003 vs. AU $31,190). In the Australian context,
      at the willingness-to-pay threshold of AU $50,000 per QALY gain, the probability
      that rTMS was cost-effective was 73%. Sensitivity analyses confirmed the
      superiority of rTMS in terms of value for money compared with antidepressant
      medications. CONCLUSIONS: Although both pharmacotherapy and rTMS are clinically
      effective treatments for major depressive disorder, rTMS is shown to outperform
      antidepressants in terms of cost-effectiveness for patients who have failed at
      least two adequate courses of antidepressant medications.

PMID- 26297088
TI  - Goal-Directed Fluid Therapy Guided by Cardiac Monitoring During High-Risk
      Abdominal Surgery in Adult Patients: Cost-Effectiveness Analysis of Esophageal
      Doppler and Arterial Pulse Pressure Waveform Analysis.
AB  - BACKGROUND: Several minimally invasive techniques for cardiac output monitoring
      such as the esophageal Doppler (ED) and arterial pulse pressure waveform analysis
      (APPWA) have been shown to improve surgical outcomes compared with conventional
      clinical assessment (CCA). OBJECTIVE: To evaluate the cost-effectiveness of these
      techniques in high-risk abdominal surgery from the perspective of the French
      public health insurance fund. METHODS: An analytical decision model was
      constructed to compare the cost-effectiveness of ED, APPWA, and CCA.
      Effectiveness data were defined from meta-analyses of randomized clinical trials.
      The clinical end points were avoidance of hospital mortality and avoidance of
      major complications. Hospital costs were estimated by the cost of corresponding
      diagnosis-related groups. RESULTS: Both goal-directed therapy strategies
      evaluated were more effective and less costly than CCA. Perioperative mortality
      and the rate of major complications were reduced by the use of ED and APPWA. Cost
      reduction was mainly due to the decrease in the rate of major complications.
      APPWA was dominant compared with ED in 71.6% and 27.6% and dominated in 23.8% and
      20.8% of the cases when the end point considered was "major complications
      avoided" and "death avoided," respectively. Regarding cost per death avoided,
      APPWA was more likely to be cost-effective than ED in a wide range of willingness
      to pay. CONCLUSIONS: Cardiac output monitoring during high-risk abdominal surgery
      is cost-effective and is associated with a reduced rate of hospital mortality and
      major complications, whatever the device used. The two devices evaluated had
      negligible costs compared with the observed reduction in hospital costs. Our
      comparative studies suggest a larger effect with APPWA that needs to be confirmed
      by further studies.

PMID- 26297089
TI  - Linezolid Versus Vancomycin in the Empiric Treatment of Nosocomial Pneumonia: A
      Cost-Utility Analysis Incorporating Results from the ZEPHyR Trial.
AB  - OBJECTIVE: To examine the cost-effectiveness of vancomycin versus linezolid in
      the empiric treatment of nosocomial pneumonias incorporating results from a
      recent prospective, double-blind, multicenter, controlled trial in adults with
      suspected methicillin-resistant Staphylococcus aureus (MRSA) nosocomial
      pneumonia. METHODS: A decision-analytic model examining the cost-effectiveness of
      linezolid versus vancomycin for the empiric treatment of nosocomial pneumonia was
      created. Publicly available cost, efficacy, and utility data populated relevant
      model variables. A probabilistic sensitivity analysis varied parameters in 10,000
      Monte-Carlo simulations, and univariate sensitivity analyses assessed the impact
      of model uncertainties and the robustness of our conclusions. RESULTS: Results
      indicated that the cost per quality-adjusted life-year (QALY) increased 6%
      ($22,594 vs. $23,860) by using linezolid versus vancomycin for nosocomial
      pneumonia. The incremental cost per QALY gained by using linezolid over
      vancomycin was $6,089, and the incremental cost per life saved was $68,615 with
      the use of linezolid. Vancomycin dominated linezolid in the subset of patients
      with documented MRSA. The incremental cost per QALY gained using linezolid if no
      mortality benefit exists between agents or a 60-day time horizon was analyzed was
      $19,608,688 and $443,662, respectively. CONCLUSIONS: Linezolid may be a cost
      effective alternative to vancomycin in the empiric treatment of patients with
      suspected MRSA nosocomial pneumonia; however, results of our model were highly
      variable on a number of important variables and assumptions including mortality
      differences and time frame analyzed.

PMID- 26297090
TI  - Cost-Effectiveness Analysis of a Television Campaign to Promote Seasonal
      Influenza Vaccination Among the Elderly.
AB  - BACKGROUND: The U.S. policy goals regarding influenza vaccination coverage rate
      among the elderly include the increase in the coverage rate and the elimination
      of disparities across racial/ethnic groups. OBJECTIVE: To examine the potential
      effectiveness of a television (TV) campaign to increase seasonal influenza
      vaccination among the elderly. METHODS: We estimated the incremental cost
      effectiveness ratio (ICER, defined as incremental cost per additionally
      vaccinated Medicare individual) of a hypothetical nationwide TV campaign for
      influenza vaccination compared with no campaign. We measured the effectiveness of
      the nationwide TV campaign (advertised once a week at prime time for 30 seconds)
      during a 17-week influenza vaccination season among four racial/ethnic elderly
      groups (N=39 million): non-Hispanic white (W), non-Hispanic African American
      (AA), English-speaking Hispanic (EH), and Spanish-speaking Hispanic (SH).
      RESULTS: The hypothetical campaign cost was $5,960,000 (in 2012 US dollars). The
      estimated campaign effectiveness ranged from -1.1% (the SH group) to 1.42% (the W
      group), leading to an increased disparity in influenza vaccination among non
      Hispanic white and non-Hispanic African American (W-AA) groups (0.6 percentage
      points), W-EH groups (0.1 percentage points), and W-SH groups (1.5 percentage
      points). The estimated ICER was $23.54 (95% confidence interval $14.21-$39.37)
      per additionally vaccinated Medicare elderly in a probabilistic analysis.
      Race/ethnicity-specific ICERs were lowest among the EH group ($22.27), followed
      by the W group ($22.47) and the AA group ($30.55). The nationwide TV campaign was
      concluded to be reasonably cost-effective compared with a benchmark intervention
      (with ICER $44.39 per vaccinated individual) of a school-located vaccination
      program. Break-even analyses estimated the maximum acceptable campaign cost to be
      $14,870,000, which was comparable to the benchmark ICER. CONCLUSIONS: The results
      could justify public expenditures on the implementation of a future nationwide TV
      campaign, which should include multilingual campaigns, for promoting seasonal
      influenza vaccination.

PMID- 26297091
TI  - Cost-Effectiveness of a Nonpharmacological Intervention in Pediatric Burn Care.
AB  - OBJECTIVE: To report the cost-effectiveness of a tailored handheld computerized
      procedural preparation and distraction intervention (Ditto) used during pediatric
      burn wound care in comparison to standard practice. METHODS: An economic
      evaluation was performed alongside a randomized controlled trial of 75 children
      aged 4 to 13 years who presented with a burn to the Royal Children's Hospital,
      Brisbane, Australia. Participants were randomized to either the Ditto
      intervention (n = 35) or standard practice (n = 40) to measure the effect of the
      intervention on days taken for burns to re-epithelialize. Direct medical, direct
      nonmedical, and indirect cost data during burn re-epithelialization were
      extracted from the randomized controlled trial data and combined with scar
      management cost data obtained retrospectively from medical charts. Nonparametric
      bootstrapping was used to estimate statistical uncertainty in cost and effect
      differences and cost-effectiveness ratios. RESULTS: On average, the Ditto
      intervention reduced the time to re-epithelialize by 3 days at AU$194 less cost
      for each patient compared with standard practice. The incremental cost
      effectiveness plane showed that 78% of the simulated results were within the more
      effective and less costly quadrant and 22% were in the more effective and more
      costly quadrant, suggesting a 78% probability that the Ditto intervention
      dominates standard practice (i.e., cost-saving). At a willingness-to-pay
      threshold of AU$120, there is a 95% probability that the Ditto intervention is
      cost-effective (or cost-saving) against standard care. CONCLUSIONS: This economic
      evaluation showed the Ditto intervention to be highly cost-effective against
      standard practice at a minimal cost for the significant benefits gained,
      supporting the implementation of the Ditto intervention during burn wound care.

PMID- 26297092
TI  - Quality of Life and Utility Measurement in a Large Clinical Trial Sample of
      Patients with Mild to Moderate Alzheimer's Disease: Determinants and Level of
      Changes Observed.
AB  - OBJECTIVE: To evaluate the performance (in terms of responsiveness to change,
      associations with other criterion standards, and indicators of Alzheimer's
      disease [AD] severity) of a quality-of-life measure (Quality of Life in
      Alzheimer's Disease [QOL-AD]) and a health utility measure (Health Utilities
      Index Mark 3 [HUI-3]) from two recently completed clinical trials of a new drug
      for AD. METHODS: Change from baseline scores was calculated, and treatment
      effects were analyzed using mixed models for repeated measures. Three separate
      models were then estimated to examine the association between the quality-of
      life/utility end points and the clinical and other health outcome end points
      measured during the trials, including cognition, function, behavior, and
      dependence. RESULTS: The performance of the two measures differed. Subject
      assessed QOL-AD was found to be weakly associated with clinical measures of
      cognition, and with caregiver reports of function, behavior, and dependence, and
      showed little movement over time and did not appear to differ by baseline AD
      severity. Proxy-assessed QOL-AD scores were consistently lower than subject
      assessed scores, and the level of decline in QOL-AD was greater using proxy
      assessed QOL-AD. Proxy-assessed HUI-3 scores were more strongly associated with
      clinical measures of cognition, function, behavior, and dependence than the
      subject- and proxy-assessed QOL-AD scores. Larger proportionate changes over 78
      weeks were observed with HUI-3 scores and greater separation in HUI-3 scores by
      baseline severity. CONCLUSIONS: Subject-assessed QOL-AD is less likely than proxy
      assessed QOL-AD to respond to changes in clinical measures used to track
      progression in clinical trials of subjects with mild to moderate AD. Proxy
      assessed HUI-3 assessments were more in line with other outcome assessments and
      could therefore be better outcome measures to evaluate clinical progression in
      mild to moderate AD.

PMID- 26297093
TI  - An Evaluation of Health Service Impacts Consequent to Switching from Brand to
      Generic Venlafaxine in New Zealand under Conditions of Price Neutrality.
AB  - OBJECTIVE: To study the health impact on adult New Zealand patients who switch
      from originator brand to generic venlafaxine. METHODS: The national pharmacy
      database was used to select patients using venlafaxine for at least 6 months.
      Switchers and nonswitchers were identified, and switch behavior was compared for
      a 12-month follow-up period. Change in health service use following switching was
      also compared between switchers and nonswitchers including use of the emergency
      department, hospital, and specialist outpatient services over the same period.
      RESULTS: Approximately 12% of all originator brand users switched to generic
      venlafaxine, at least half of whom continued to use the generic throughout the
      follow-up period to August 1, 2012. Almost 60% of new users of the generic
      venlafaxine, however, switched to using the originator brand. Aside from a slight
      reduction in the use of outpatient services among switchers, there were no
      significant differences in health services use between switchers and nonswitchers
      for either existing or new venlafaxine users. CONCLUSIONS: Although both products
      remain fully subsidized and available, there is little incentive for prescribers,
      pharmacists, or patients to switch to the less expensive generic brand. If
      savings to the national New Zealand budget are to be realized, additional policy
      measures should be implemented to minimize incentives for multiple and reverse
      switching, and prescribers, as key opinion leaders, could take the lead in
      promoting generics to their patients.

PMID- 26297094
TI  - The Social Distribution of Health: Estimating Quality-Adjusted Life Expectancy in
      England.
AB  - OBJECTIVE: To model the social distribution of quality-adjusted life expectancy
      (QALE) in England by combining survey data on health-related quality of life with
      administrative data on mortality. METHODS: Health Survey for England data sets
      for 2010, 2011, and 2012 were pooled (n = 35,062) and used to model health
      related quality of life as a function of sex, age, and socioeconomic status
      (SES). Office for National Statistics mortality rates were used to construct life
      tables for age-sex-SES groups. These quality-of-life and length-of-life estimates
      were then combined to predict QALE as a function of these characteristics.
      Missing data were imputed, and Monte-Carlo simulation was used to estimate
      standard errors. Sensitivity analysis was conducted to explore alternative
      regression models and measures of SES. RESULTS: Socioeconomic inequality in QALE
      at birth was estimated at 11.87 quality-adjusted life-years (QALYs), with a sex
      difference of 1 QALY. When the socioeconomic-sex subgroups are ranked by QALE, a
      differential of 10.97 QALYs is found between the most and least healthy quintile
      groups. This differential can be broken down into a life expectancy difference of
      7.28 years and a quality-of-life adjustment of 3.69 years. CONCLUSIONS: The
      methods proposed in this article refine simple binary quality-adjustment measures
      such as the widely used disability-free life expectancy, providing a more
      accurate picture of overall health inequality in society than has hitherto been
      available. The predictions also lend themselves well to the task of evaluating
      the health inequality impact of interventions in the context of cost
      effectiveness analysis.

PMID- 26297095
TI  - Can a Joint Assessment Provide Relevant Information for National/Local Relative
      Effectiveness Assessments? An In-Depth Comparison of Pazopanib Assessments.
AB  - BACKGROUND: In many European jurisdictions, relative effectiveness assessments
      (REAs) of pharmaceuticals are performed during the reimbursement decision-making
      process. International collaboration in the production of these assessments may
      prevent the duplication of information in various jurisdictions. A first pilot of
      a joint REA (pazopanib for the treatment of renal cell carcinoma) was published
      in 2011. OBJECTIVE: The objective was to investigate how well the methods used in
      the joint REA match the methods used in the national/local assessments on the
      same topic. METHODS: National/local assessments from European jurisdictions,
      available in English language, were identified through a literature search and an
      e-mail request to health technology assessment organizations. Data were
      abstracted from joint and national/local assessments using a structured data
      abstraction form. Results were compared for differences and similarities.
      RESULTS: In total, five national/local reports were included (Belgium,
      England/Wales, France, The Netherlands, and Scotland). The general methods
      (indication, main comparator, main end points, main trial) were similar. The
      details of the assessment (e.g., exact wording of indication, additional
      comparators, additional trials included, and method of indirect comparison),
      however, varied. Despite these differences, the joint REA included nearly all
      comparators, end points, trials, and methods of analysis that were used in
      national/local REA reports. CONCLUSIONS: This study has shown overlap in the
      methods national/local REA bodies in Europe have chosen for a pazopanib REA for
      renal cell carcinoma, except for the use and methods of indirect comparisons.
      Although some additional comparators and outcomes differed between national/local
      REAs, they can be captured in a comprehensive joint REA.

PMID- 26297096
TI  - Extending Treatment Networks in Health Technology Assessment: How Far Should We
      Go?
AB  - BACKGROUND: Network meta-analysis may require substantially more resources than
      does a standard systematic review. One frequently asked question is "how far
      should I extend the network and which treatments should I include?" OBJECTIVE: To
      explore the increase in precision from including additional evidence. METHODS: We
      assessed the benefit of extending treatment networks in terms of precision of
      effect estimates and examined how this depends on network structure and relative
      strength of additional evidence. We introduced a "star"-shaped network. Network
      complexity is increased by adding more evidence connecting treatments under five
      evidence scenarios. We also examined the impact of heterogeneity and absence of
      evidence facilitating a "first-order" indirect comparison. RESULTS: In all
      scenarios, extending the network increased the precision of the A versus B
      treatment effect. Under a fixed-effect model, the increase in precision was
      modest when the existing direct A versus B evidence was already strong and was
      substantial when the direct evidence was weak. Under a random-effects model, the
      gain in precision was lower when heterogeneity was high. When evidence is
      available for all "first-order" indirect comparisons, including second-order
      evidence has limited benefit for the precision of the A versus B estimate. This
      is interpreted as a "ceiling effect." CONCLUSIONS: Including additional evidence
      increases the precision of a "focal" treatment comparison of interest. Once the
      comparison of interest is connected to all others via "first-order" indirect
      evidence, there is no additional benefit in including higher order comparisons.
      This conclusion is generalizable to any number of treatment comparisons, which
      would then all be considered "focal." The increase in precision is modest when
      direct evidence is already strong, or there is a high degree of heterogeneity.

PMID- 26297097
TI  - When Does FDAMA Section 114 Apply? Ten Case Studies.
AB  - BACKGROUND: Section 114 of the Food and Drug Administration Modernization Act of
      1997 regulates the promotion of health economic information by pharmaceutical
      companies to US health plans. Greater clarity is important given demands by
      payers and other stakeholders for evidence of value. OBJECTIVES: To develop
      hypothetical case studies of health economic promotions to examine legal and
      policy implications. METHODS: We constructed for pedagogical purposes 10
      categories of potential health economic promotions. We generated hypothetical
      case studies for each category, including questions about whether each might be
      allowable under Section 114. The case studies were developed around the following
      categories: 1) costing out on-label clinical end points; 2) promotion of a
      costing exercise to physicians working in an accountable care organization
      setting; 3) burden-of-illness claims; 4) economic analysis of a formulary
      restriction policy; 5) extrapolations to doses, populations, or settings not
      covered in trials; 6) adherence claims; 7) "utilization of care" as a secondary
      end point in randomized clinical trials; 8) costing out a competitor drug's
      adverse event; 9) economic analysis of comparative effectiveness claims using an
      indirect treatment comparison; and 10) extrapolating from surrogate to long-term
      outcomes in an economic model. DISCUSSION: Most cases seem to fall into a gray
      zone given haziness around what constitutes "competent and reliable evidence" and
      "directly relate[d]" to an approved indication. In practice, it is difficult to
      know what the section allows given the imprecision of the statute and lack of
      guidance about its scope. CONCLUSION: Ideally, future guidance will provide
      clarity and flexibility.

PMID- 26297098
TI  - Initial Medication Adherence-Review and Recommendations for Good Practices in
      Outcomes Research: An ISPOR Medication Adherence and Persistence Special Interest
      Group Report.
AB  - BACKGROUND: Positive associations between medication adherence and beneficial
      outcomes primarily come from studying filling/consumption behaviors after therapy
      initiation. Few studies have focused on what happens before initiation, the point
      from prescribing to dispensing of an initial prescription. OBJECTIVE: Our
      objective was to provide guidance and encourage high-quality research on the
      relationship between beneficial outcomes and initial medication adherence (IMA),
      the rate initially prescribed medication is dispensed. METHODS: Using generic
      adherence terms, an international research panel identified IMA publications from
      1966 to 2014. Their data sources were classified as to whether the primary source
      reflected the perspective of a prescriber, patient, or pharmacist or a combined
      perspective. Terminology and methodological differences were documented among
      core (essential elements of presented and unpresented prescribing events and
      claimed and unclaimed dispensing events regardless of setting), supplemental
      (refined for accuracy), and contextual (setting-specific) design parameters.
      Recommendations were made to encourage and guide future research. RESULTS: The 45
      IMA studies identified used multiple terms for IMA and operationalized
      measurements differently. Primary data sources reflecting a prescriber's and
      pharmacist's perspective potentially misclassified core parameters more often
      with shorter/nonexistent pre- and postperiods (1-14 days) than did a combined
      perspective. Only a few studies addressed supplemental issues, and minimal
      contextual information was provided. CONCLUSIONS: General recommendations are to
      use IMA as the standard nomenclature, rigorously identify all data sources, and
      delineate all design parameters. Specific methodological recommendations include
      providing convincing evidence that initial prescribing and dispensing events are
      identified, supplemental parameters incorporating perspective and substitution
      biases are addressed, and contextual parameters are included.

PMID- 26297099
TI  - A Systematic Review on the Cost-Effectiveness of Genetic and Electrocardiogram
      Testing for Long QT Syndrome in Infants and Young Adults.
AB  - BACKGROUND: Recent improvements in the identification of the genetic basis of
      long QT syndrome (LQTS) have led to significant changes in the diagnosis and
      management of this life-threatening condition. Genetic and electrocardiogram
      (ECG) tests are the most relevant examples among testing strategies for LQTS, yet
      their cost-effectiveness remains controversial. OBJECTIVE: The aim of this work
      was to review the available evidence on the cost-effectiveness of genetic and ECG
      testing strategies for the diagnosis of LQTS. METHODS: We performed a systematic
      review of the literature on the cost-effectiveness of genetic and ECG screening
      strategies for the early detection of LQTS using MEDLINE, EMBASE, and CRD
      databases between 2000 and 2013. A weighted version of Drummond checklist was
      instrumental in further assessing the quality of the included studies. RESULTS:
      We identified four eligible articles. Among them, genetic testing in the early
      detection of LQTS was cost-effective compared with no testing in symptomatic
      cases and not cost-effective when compared with watchful waiting in asymptomatic
      first-degree relatives of patients with established LQTS although it reached cost
      effectiveness in higher risk subgroups, whereas ECG testing in neonates was
      highly cost-effective when compared with any screening strategy. CONCLUSIONS:
      LQTS profiling and patients' stratification have the potential to improve the
      disease management. Because of the limited current knowledge in this field, the
      present review recommends to perform further cost-effectiveness evaluations of
      the genetic and ECG screening alternatives, especially within European health
      care systems, which are still not available in the literature on genetic testing.

PMID- 26297100
TI  - Investigating the Generalizability of Economic Evaluations Conducted in Italy: A
      Critical Review.
AB  - OBJECTIVES: To assess the methodological quality of Italian health economic
      evaluations and their generalizability or transferability to different settings.
      METHODS: A literature search was performed on the PubMed search engine to
      identify trial-based, nonexperimental prospective studies or model-based full
      economic evaluations carried out in Italy from 1995 to 2013. The studies were
      randomly assigned to four reviewers who applied a detailed checklist to assess
      the generalizability and quality of reporting. The review process followed a
      three-step blinded procedure. The reviewers who carried out the data extraction
      were blind as to the name of the author(s) of each study. Second, after the first
      review, articles were reassigned through a second blind randomization to a second
      reviewer. Finally, any disagreement between the first two reviewers was solved by
      a senior researcher. RESULTS: One hundred fifty-one economic evaluations
      eventually met the inclusion criteria. Over time, we observed an increasing
      transparency in methods and a greater generalizability of results, along with a
      wider and more representative sample in trials and a larger adoption of
      transition-Markov models. However, often context-specific economic evaluations
      are carried out and not enough effort is made to ensure the transferability of
      their results to other contexts. In recent studies, cost-effectiveness analyses
      and the use of incremental cost-effectiveness ratio were preferred. CONCLUSIONS:
      Despite a quite positive temporal trend, generalizability of results still
      appears as an unsolved question, even if some indication of improvement within
      Italian studies has been observed.

PMID- 26297101
TI  - Economic Evaluations in the Diagnosis and Management of Traumatic Brain Injury: A
      Systematic Review and Analysis of Quality.
AB  - BACKGROUND: Economic evaluations provide a unique opportunity to identify the
      optimal strategies for the diagnosis and management of traumatic brain injury
      (TBI), for which uncertainty is common and the economic burden is substantial.
      OBJECTIVE: The objective of this study was to systematically review and examine
      the quality of contemporary economic evaluations in the diagnosis and management
      of TBI. METHODS: Two reviewers independently searched MEDLINE, EMBASE, Cochrane
      Central Register of Controlled Trials, NHS Economic Evaluation Database, Health
      Technology Assessment Database, EconLit, and the Tufts CEA Registry for
      comparative economic evaluations published from 2000 onward (last updated on
      August 30, 2013). Data on methods, results, and quality were abstracted in
      duplicate. The results were summarized quantitatively and qualitatively. RESULTS:
      Of 3539 citations, 24 economic evaluations met our inclusion criteria. Nine were
      cost-utility, five were cost-effectiveness, three were cost-minimization, and
      seven were cost-consequences analyses. Only six studies were of high quality.
      Current evidence from high-quality studies suggests the economic attractiveness
      of the following strategies: a low medical threshold for computed tomography (CT)
      scanning of asymptomatic infants with possible inflicted TBI, selective CT
      scanning of adults with mild TBI as per the Canadian CT Head Rule, management of
      severe TBI according to the Brain Trauma Foundation guidelines, management of TBI
      in dedicated neurocritical care units, and early transfer of patients with TBI
      with nonsurgical lesions to neuroscience centers. CONCLUSIONS: Threshold-guided
      CT scanning, adherence to Brain Trauma Foundation guidelines, and care for
      patients with TBI, including those with nonsurgical lesions, in specialized
      settings appear to be economically attractive strategies.

PMID- 26297102
TI  - HIV Rapid Testing in a VA Emergency Department Setting: Cost Analysis at 5 Years.
AB  - OBJECTIVES: To conduct a comprehensive cost-minimization analysis to comprehend
      the financial attributes of the first 5 years of an implementation wherein
      emergency department (ED) registered nurses administered HIV oral rapid tests to
      patients. METHODS: A health science research implementation team coordinated with
      ED stakeholders and staff to provide training, implementation guidelines, and
      support to launch ED registered nurse-administered HIV oral rapid testing.
      Deidentified quantitative data were gathered from the electronic medical records
      detailing quarterly HIV rapid test rates in the ED setting spanning the first 5
      years. Comprehensive cost analyses were conducted to evaluate the financial
      impact of this implementation. RESULTS: At 5 years, a total of 2,620 tests were
      conducted with a quarterly mean of 131 +/- 81. Despite quarterly variability in
      testing rates, regression analysis revealed an average increase of 3.58 tests per
      quarter. Over the course of this implementation, Veterans Health Administration
      policy transitioned from written to verbal consent for HIV testing, serving to
      reduce the time and cost(s) associated with the testing process. CONCLUSIONS: Our
      data indicated salient health outcome benefits for patients with respect to the
      potential for earlier detection, and associated long-run cost savings.

PMID- 26297105
TI  - Implementing classroom physical activity breaks: Associations with student
      physical activity and classroom behavior.
AB  - OBJECTIVE: To investigate the relation of classroom physical activity breaks to
      students' physical activity and classroom behavior. METHODS: Six elementary
      school districts in California implemented classroom physical activity
      interventions in 2013-2014. Students' (N=1322) accelerometer-measured moderate-to
      vigorous physical activity (MVPA) during school and teachers' (N=397) reports of
      implementation and classroom behavior were assessed in 24 schools at two time
      points (both post-intervention). Mixed-effects models accounted for nested data.
      RESULTS: Minutes/day of activity breaks was positively associated with students'
      MVPA (betas=.07-.14; ps=.012-.016). Students in classrooms with activity breaks
      were more likely to obtain 30 min/day of MVPA during school (OR=1.75; p=.002).
      Implementation was negatively associated with students having a lack of effort in
      class (beta=-.17; p=.042), and student MVPA was negatively associated with
      students being off task or inattentive in the classroom (beta=-.17; p=.042).
      Students provided with 3-4 physical activity opportunities (classroom breaks,
      recess, PE, dedicated PE teacher) had ~5 more min/day of school MVPA than
      students with no opportunities (B=1.53 min/opportunity; p=.002). CONCLUSIONS:
      Implementing classroom physical activity breaks can improve student physical
      activity during school and behavior in the classroom. Comprehensive school
      physical activity programs that include classroom-based activity are likely
      needed to meet the 30 min/day school physical activity guideline.

PMID- 26297103
TI  - The role of tissue resident cells in neutrophil recruitment.
AB  - Neutrophils are first responders of the immune system, rapidly migrating into
      affected tissues in response to injury or infection. To effectively call in this
      first line of defense, strategically placed cells within the vasculature and
      tissue respond to noxious stimuli by sending out coordinated signals that recruit
      neutrophils. Regulation of organ-specific neutrophil entry occurs at two levels.
      First, the vasculature supplying the organ provides cues for neutrophil egress
      out of the bloodstream in a manner dependent upon its unique cellular composition
      and architectural features. Second, resident immune cells and stromal cells
      within the organ send coordinated signals that guide neutrophils to their final
      destination. Here, we review recent findings that highlight the importance of
      these tissue-specific responses in the regulation of neutrophil recruitment and
      the initiation and resolution of inflammation. 

PMID- 26297104
TI  - A controlled antibiotic release system to prevent orthopedic-implant associated
      infections: An in vitro study.
AB  - A new device for local delivery of antibiotics is presented, with potential use
      as a drug-eluting fixation pin for orthopedic applications. The implant consists
      of a stainless steel hollow tubular reservoir packed with the desired antibiotic.
      Release takes place through several orifices previously drilled in the reservoir
      wall, a process that does not compromise the mechanical properties required for
      the implant. Depending on the antibiotic chosen and the number of orifices, the
      release profile can be tailored from a rapid release of the load (ca. 20h) to a
      combination of rapid initial release and slower, sustained release for a longer
      period of time (ca. 200h). An excellent bactericidal action is obtained, with 4
      log reductions achieved in as little as 2h, and total bacterial eradication in 8h
      using 6-pinholed implants filled with cefazolin. 

PMID- 26297106
TI  - Development of a text message intervention aimed at reducing alcohol-related harm
      in patients admitted to hospital as a result of injury.
AB  - BACKGROUND: Screening for alcohol misuse and brief interventions (BIs) for harm
      in trauma care settings are known to reduce alcohol intake and injury recidivism,
      but are rarely implemented. We created the content for a mobile phone text
      message BI service to reduce harmful drinking among patients admitted to hospital
      following an injury who screen positive for hazardous alcohol use. The aim of
      this study was to pre-test and refine the text message content using a robust
      contextualisation process ahead of its formal evaluation in a randomised
      controlled trial. METHODS: Pre-testing was conducted in two phases. First, in
      depth interviews were conducted with 14 trauma inpatients (16-60 years) at
      Auckland City Hospital and five key informants. Participants were interviewed
      face-to-face using a semi-structured interview guide. Topics explored included:
      opinions on text message ideas and wording, which messages did or did not work
      well and why, interactivity of the intervention, cultural relevance of messages,
      and tone of the content. In a second phase, consultation was undertaken with
      Maori (New Zealand's indigenous population) and Pacific groups to explore the
      relevance and appropriateness of the text message content for Maori and Pacific
      audiences. RESULTS: Factors identified as important for ensuring the text message
      content was engaging, relevant, and useful for recipients were: reducing the
      complexity of message content and structure; increasing the interactive
      functionality of the text message programme; ensuring an empowering tone to text
      messages; and optimising the appropriateness and relevance of text messages for
      Maori and Pacific people. The final version of the intervention (named
      'YourCall(TM)') had three pathways for people to choose between: 1) text messages
      in English with Te Reo (Maori language) words of welcome and encouragement, 2)
      text messages in Te Reo Maori, and 3) text messages in English (with an option to
      receive a greeting in Samoan, Tongan, Cook Island Maori, Niuean, Tokelauan,
      Tuvaluan, or Fijian). CONCLUSIONS: We have developed a text message intervention
      underpinned by established BI evidence and behaviour change theory and refined
      based on feedback and consultation. The next step is evaluation of the
      intervention in a randomised-controlled trial.

PMID- 26297107
TI  - Prospective randomized trial comparing laparoscopic transabdominal preperitoneal
      (TAPP) and laparoscopic totally extra peritoneal (TEP) approach for bilateral
      inguinal hernias.
AB  - INTRODUCTION: Bilateral inguinal hernias form a part of the complex spectrum of
      weakness in the region of the myopectineal orifice. Laparoscopic surgery is one
      of the standard approaches for bilateral hernias. We describe the results of a
      randomized trial that was undertaken to compare and evaluate TAPP and TEP repair
      for bilateral inguinal hernias. METHODS: Sixty patients were randomized into two
      groups. Group I (TAPP) and Group II (TEP) were compared in terms of procedure
      related variables, conversion, post-operative recovery and complications.
      Analysis was done using SPSS software version 17. RESULTS: Seventy-seven patients
      were assessed for fitness to include in the study. Seventeen patients had to be
      excluded due to either not meeting the inclusion criteria's or for not giving
      consent. The median age (52 yrs) was comparable in both groups. In Group II (TEP)
      mean operating time was 120.89 +/- 29.28 min compared to 108.16 +/- 16.10 min in
      Group I (TAPP). Post-operative pain scores were less in Group I(TAPP) at all
      levels of recording (8 h-48 h), though most patients required injectable
      analgesic for 32 h in both groups (p-value 0.029). Subcutaneous emphysema was
      more commonly noted in the Group II (TEP) (p-value 0.038). In Group I (TAPP) mean
      hospital stay was 52.0 +/- 14.21 h while in Group II (TEP) it was 52.29 +/- 9.36
      h (p-value 0.427). Mean time for return to work was 11.8 +/- 2.35 days in Group I
      (TAPP) and 12.41 +/- 2.22 days in Group II (TEP) (p-value 0.339). CONCLUSION: The
      procedures though different in approach were quite similar in outcome. Mean
      operating time was increased in the TEP repairs along with immediate post
      operative pain scores. The pattern of some complications like subcutaneous
      emphysema was significantly more in the TEP group while minor vascular injury
      though not significant was different in both groups. The indirect cost incurred
      from consumables did not vary other than need for more tacks in the TAPP group.

PMID- 26297108
TI  - Mesophyll conductance to CO2 and Rubisco as targets for improving intrinsic water
      use efficiency in C3 plants.
AB  - Water limitation is a major global constraint for plant productivity that is
      likely to be exacerbated by climate change. Hence, improving plant water use
      efficiency (WUE) has become a major goal for the near future. At the leaf level,
      WUE is the ratio between photosynthesis and transpiration. Maintaining high
      photosynthesis under water stress, while improving WUE requires either increasing
      mesophyll conductance (gm ) and/or improving the biochemical capacity for CO2
      assimilation-in which Rubisco properties play a key role, especially in C3 plants
      at current atmospheric CO2 . The goals of the present analysis are: (1) to
      summarize the evidence that improving gm and/or Rubisco can result in increased
      WUE; (2) to review the degree of success of early attempts to genetically
      manipulate gm or Rubisco; (3) to analyse how gm , gsw and the Rubisco's maximum
      velocity (Vcmax ) co-vary across different plant species in well-watered and
      drought-stressed conditions; (4) to examine how these variations cause
      differences in WUE and what is the overall extent of variation in individual
      determinants of WUE; and finally, (5) to use simulation analysis to provide a
      theoretical framework for the possible control of WUE by gm and Rubisco catalytic
      constants vis-a-vis gsw under water limitations. 

PMID- 26297109
TI  - Necrotizing Meningoencephalitis in a Captive Black and White Ruffed Lemur
      (Varecia variegata variegata) Caused by Acanthamoeba T4 Genotype.
AB  - A mature male, black and white ruffed lemur (Varecia variegata variegata) died in
      a zoological garden after a 4-day history of lethargy and non-responsive
      convulsions. Necropsy and histopathological examinations revealed acute
      necrotizing and haemorrhagic meningoencephalitis with intralesional amoebas
      confirmed by immunohistochemistry. Acanthamoeba T4 genotype was identified as the
      causative agent of the brain lesion, based on amplification and sequencing of 18S
      ribosomal RNA genes. The presence of free-living amoebas in water and mud from
      the lemur's environment was investigated by morphological and molecular analyses.
      The two predominant genera, representing 80% of isolated amoebas, were Naegleria
      spp. and Acanthamoeba spp. All Acanthamoeba isolates belonged to the T4 genotype.
      To the author's knowledge, this is the first report of a meningoencephalitis due
      to Acanthamoeba T4 genotype in Lemuridae with concurrent analysis of pathological
      tissues and environment. 

PMID- 26297110
TI  - Clinical and laboratory characteristics of ocular syphilis: a new face in the era
      of HIV co-infection.
AB  - BACKGROUND: Ocular syphilis is reemerging as an important cause of uveitis in the
      new era of common co-infection with HIV. This study will reveal the clinical and
      laboratory characteristics in the group of individuals co-infected with ocular
      syphilis and HIV compared with HIV-negative individuals. In this retrospective
      observational case series, medical records of patients diagnosed with ocular
      syphilis with serologic support from 2008 to 2014 were reviewed. Ocular and
      systemic manifestation and laboratory profiles were reviewed. RESULTS: Twenty
      nine eyes of 16 consecutive patients (10 HIV-positive and 6 HIV-negative) were
      included. All patients were males, and mean age of onset for ocular syphilis was
      43 (mean 42.65 +/- 13.13). In both HIV-positive and HIV-negative groups, ocular
      manifestations of syphilis were variable including anterior uveitis (4 eyes),
      posterior uveitis (8 eyes), panuveitis (13 eyes), and isolated papillitis (4
      eyes). In HIV-positive patients, panuveitis was the most common feature (12/18
      eyes, 67 %) and serum rapid plasma reagin (RPR) titers were significantly higher
      (range 1:64-1:16,348; mean 1:768; p = 0.018) than in HIV-negative patients. Upon
      the diagnosis of ocular syphilis in HIV-positive patients, HIV-1 viral load was
      high (median 206,887 copies/ml) and CD4 cell count ranged from 127 to 535
      cells/ml (mean 237 +/- 142; median 137). Regardless of HIV status, cerebrospinal
      fluid (CSF) exam was frequently abnormal: positive CSF fluorescent treponemal
      antibody absorption (FTA-ABS) or Venereal Disease Research Laboratory (VDRL) test
      results in seven patients or either elevated CSF WBC count or elevated CSF
      protein in six patients. CONCLUSIONS: Our results reveal that the patients with
      ocular syphilis with high serum RPR titers may have concomitant HIV infection
      requiring further testing for HIV status and ocular syphilis is likely associated
      with the central nervous system involvement and therefore needs to be managed
      according to the treatment recommendations for neurosyphilis.

PMID- 26297111
TI  - Erratum: Timp1 interacts with beta-1 integrin and CD63 along melanoma genesis and
      confers anoikis resistance by activating PI3-K signaling pathway independently of
      Akt phosphorylation.

PMID- 26297112
TI  - Prompt Diagnosis of an Unusual Cause of Obstructive Shock Using Point-of-Care
      Ultrasound.
AB  - BACKGROUND: The patient presenting in an undifferentiated shock state can produce
      a diagnostic challenge for even the most seasoned clinician. CASE REPORT: We
      present an unusual case of an elderly woman in obstructive shock from a large
      atrial mass that was promptly diagnosed with point-of-care ultrasound. WHY SHOULD
      AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Ultrasound is a non-invasive tool that
      can help facilitate the early diagnosis of a patient in undifferentiated shock.

PMID- 26297113
TI  - Direct noninvasive estimation of myocardial tricarboxylic acid cycle flux in vivo
      using hyperpolarized 13C magnetic resonance.
AB  - BACKGROUND: The heart relies on continuous energy production and imbalances
      herein impair cardiac function directly. The tricarboxylic acid (TCA) cycle is
      the primary means of energy generation in the healthy myocardium, but direct
      noninvasive quantification of metabolic fluxes is challenging due to the low
      concentration of most metabolites. Hyperpolarized (13)C magnetic resonance
      spectroscopy (MRS) provides the opportunity to measure cellular metabolism in
      real time in vivo. The aim of this work was to noninvasively measure myocardial
      TCA cycle flux (VTCA) in vivo within a single minute. METHODS AND RESULTS:
      Hyperpolarized [1-(13)C]acetate was administered at different concentrations in
      healthy rats. (13)C incorporation into [1-(13)C]acetylcarnitine and the TCA cycle
      intermediate [5-(13)C]citrate was dynamically detected in vivo with a time
      resolution of 3s. Different kinetic models were established and evaluated to
      determine the metabolic fluxes by simultaneously fitting the evolution of the
      (13)C labeling in acetate, acetylcarnitine, and citrate. VTCA was estimated to be
      6.7+/-1.7 MUmol.g(-1).min(-1) (dry weight), and was best estimated with a model
      using only the labeling in citrate and acetylcarnitine, independent of the
      precursor. The TCA cycle rate was not linear with the citrate-to-acetate
      metabolite ratio, and could thus not be quantified using a ratiometric approach.
      The (13)C signal evolution of citrate, i.e. citrate formation was independent of
      the amount of injected acetate, while the (13)C signal evolution of
      acetylcarnitine revealed a dose dependency with the injected acetate. The (13)C
      labeling of citrate did not correlate to that of acetylcarnitine, leading to the
      hypothesis that acetylcarnitine formation is not an indication of mitochondrial
      TCA cycle activity in the heart. CONCLUSIONS: Hyperpolarized [1-(13)C]acetate is
      a metabolic probe independent of pyruvate dehydrogenase (PDH) activity. It allows
      the direct estimation of VTCA in vivo, which was shown to be neither dependent on
      the administered acetate dose nor on the (13)C labeling of acetylcarnitine.
      Dynamic (13)C MRS coupled to the injection of hyperpolarized [1-(13)C]acetate can
      enable the measurement of metabolic changes during impaired heart function.

PMID- 26297114
TI  - Epitope characterization of an anti-PIVKA-II antibody and evaluation of a fully
      automated chemiluminescent immunoassay for PIVKA-II.
AB  - OBJECTIVES: Protein induced by vitamin K absence or antagonist-II (PIVKA-II) has
      been used as a tumor marker to aid in the diagnosis of hepatocellular carcinoma
      (HCC). We developed an anti-PIVKA-II monoclonal antibody, 3C10, and a fully
      automated quantitative immunoassay for PIVKA-II on the ARCHITECT(r) i-systems.
      The aim of this study was to characterize the epitope of 3C10 and to evaluate the
      reactivity to PIVKA-II of this assay. METHODS: The epitope characterization was
      examined by using prothrombin gamma-carboxyglutamic acid residues (Gla) domain
      polypeptides which are amino acid residues 17-27 that include four Gla residues
      at positions 19, 20, 25 and 26. The correlation with Picolumi PIVKA-II MONO
      (Eidia, Tokyo, Japan) and tube type equivalency was evaluated by using the
      developed fully automated quantitative immunoassay. RESULTS: Peptides having
      glutamic acid residues (Glu) at Gla domains strongly reacted to 3C10 but lost
      reactivity when the Glu at positions 19 or 20 was changed to Gla. The results
      were equivalent with an existing in vitro diagnostics product for PIVKA-II using
      the MU-3 antibody. A correlation study with the Picolumi PIVKA-II MONO gave a
      correlation coefficient of 0.99 and a regression slope of 0.92. No difference
      between a plain serum tube and a rapid serum tube including thrombin (RST) was
      observed on ARCHITECT PIVKA-II. CONCLUSIONS: The results demonstrate that this
      anti-PIVKA-II antibody detects equivalent epitopes with MU-3 and has equivalent
      reactivity to PIVKA-II as MU-3. Moreover, the ARCHITECT PIVKA-II assay has good
      correlation with the existing PIVKA-II product, and is applicable for use with
      RST.

PMID- 26297115
TI  - Challenges in harmonizing integrated healthcare network laboratories: multi
      center evaluation of the hCG5 assay.
AB  - BACKGROUND: Beckman Coulter recently introduced a new hCG assay manufactured for
      the Access 2 and DxI platforms. This assay is the first to use the 5th
      International Standard (5th IS) as its primary calibration material. Clinical
      laboratories are required to validate the method performance before testing and
      reporting patient results. METHODS: Beckman Coulter Access 2 instruments (n=41)
      across Kaiser Permanente Northern California were evaluated for their performance
      characteristics using the hCG5 reagent. Precision, linearity, dilution
      verification, and patient sample comparisons were performed on each instrument.
      RESULTS: The assay was linear up to 1350IU/L. Intra-day and inter-day precision
      ranged from 1.0%-3.3% and 1.8-7.3%, respectively, for the low QC material (mean
      concentration 4.6IU/L). Percent bias between the previous assay (hCG2) and the
      hCG5 assay was 3.2 to 22.7% for hCG concentrations <1000IU/L and -2.9 to 30% for
      concentrations >1000IU/L. On board and manual dilutions agreed within 15%
      following proper adjustment of the instrument dilution factor. CONCLUSIONS:
      Achieving Access 2 inter-instrument agreement on specimens needing dilutions
      (hCG>1350IU/L) requires validation of the on board dilution factor. Laboratories
      should use QC material above the linear range to monitor instrument dilution
      accuracy and precision.

PMID- 26297116
TI  - Transference of CALIPER pediatric reference intervals to biochemical assays on
      the Roche cobas 6000 and the Roche Modular P.
AB  - OBJECTIVES: The Canadian Laboratory Initiative on Pediatric Reference Intervals
      (CALIPER) has recently established pediatric age- and sex-specific reference
      intervals for over 85 biochemical markers on the Abbott Architect system.
      Previously, CALIPER reference intervals for several biochemical markers were
      successfully transferred from Abbott assays to Roche, Beckman, Ortho, and Siemens
      assays. This study further broadens the CALIPER database by performing
      transference and verification for 52 biochemical assays on the Roche cobas 6000
      and the Roche Modular P. DESIGN AND METHODS: Using CLSI C28-A3 and EP9-A2
      guidelines, transference of the CALIPER reference intervals was attempted for 16
      assays on the Roche cobas 6000 and 36 on the Modular P. Calculated reference
      intervals were further verified using 100 healthy CALIPER samples. RESULTS: Most
      assays showed strong correlation between assay systems and were transferable from
      Abbott to the Roche cobas 6000 (81%) and the Modular P (86%). Bicarbonate and
      magnesium were not transferable on either system and calcium and prealbumin were
      not transferable to the Modular P. Of the transferable analytes, 62% and 61% were
      verified on the cobas 6000 and the Modular P, respectively. CONCLUSIONS: This
      study extends the utility of the CALIPER database to two additional analytical
      systems, which facilitates the broad application of CALIPER reference intervals
      at pediatric centers utilizing Roche biochemical assays. Transference studies
      across different analytical platforms can later be collectively analyzed in an
      attempt to develop common reference intervals across all clinical chemistry
      instruments to harmonize laboratory test interpretation in diagnosis and
      monitoring of pediatric disease.

PMID- 26297117
TI  - Direct assay of iduronate-2-sulfatase for Hunter disease using UPLC-tandem mass
      spectrometry and fluorogenic substrate.
AB  - OBJECTIVE: We devised iduronate-2-sulfatase (IDS) enzyme activity assays by
      combining fluorometric substrate and LC-MS/MS based detection. DESIGN AND
      METHODS: 4-Methylumbelliferyl alpha-L-idopyranosiduronic acid 2-sulfate (IDS-S)
      was used as a substrate for IDS. Its enzymatic product, 4-methylumbelliferyl
      alpha-L-idopyranosiduronic acid (IDS-P) and internal standard, 4
      methylumbelliferyl alpha-L-idopyranoside (IDS-IS), were directly measured by UPLC
      MS/MS. We determined the precision of our enzyme assay and the effects of sample
      amounts and incubation time based on the results. Dried blood spots (DBSs) of 110
      normal newborns and three patients with Hunter disease were analyzed. RESULTS:
      IDS-IS, IDS-P and IDS-S were fully separated using UPLC without any ion
      suppressions. The intra- and inter-assay precisions were 8.5-10.5% and 11.9
      15.3%, respectively. The amount of product obtained was proportional to the
      number of DBSs and increased linearly with the incubation period from 0 to 15 h.
      The enzyme activities in DBSs from three patients with MPS II were markedly lower
      than those in the DBSs of 110 normal newborns. CONCLUSION: To the best of our
      knowledge, this is the first report describing the use of LC-MS/MS for the
      diagnosis of Hunter disease with a commercially available substrate. Our method
      would be a rapid and effective screening tool for the diagnosis of Hunter disease
      with further study.

PMID- 26297118
TI  - Evaluation of a particle enhanced turbidimetric assay for the measurement of
      neutrophil gelatinase-associated lipocalin in plasma and urine on Architect-8000:
      Analytical performance and establishment of reference values.
AB  - OBJECTIVES: Neutrophil gelatinase-associated lipocalin (NGAL) is a promising
      biomarker for acute kidney injury. NGAL can be measured in both blood and urine.
      Apart from kidney injury, NGAL levels in both plasma and urine can be influenced
      by various pathological situations. Accurate evaluation and comparison of results
      deriving from clinical studies require robust assays, appropriate specimen
      handling and reference intervals that will reflect its levels in a healthy
      population for both biological matrices. METHODS: We report the analytical
      validation of a latex particle-enhanced turbidimetric immunoassay (PETIA) aimed
      to measure NGAL in plasma and urine on an automated biochemistry analyzer (ABBOTT
      Architect-8000). Assay performance characteristics were evaluated using standard
      protocols. Urine and plasma specimen storage requirements were determined and
      reference ranges for blood and urine were determined using healthy controls.
      RESULTS: The assay is precise (total CV%<4.8%), and sensitive (limit of
      quantification: 8.4 ng/mL for plasma and 9.0 ng/mL for urine), showing no hook
      effect. Calibration is stable for at least 30 days. The assay showed excellent
      linearity over the studied interval (20-4450 ng/mL). The analyte is stable at 4 
      degrees C for at least 5 days, and at 20  degrees C for 4h. Gender specific
      reference ranges for plasma (male: 38.7-157.6 ng/mL, female: 24.4-142.5 ng/mL)
      and unisex for urine (<9.0-49.41 ng/mL) are proposed. CONCLUSION: Our data
      indicate that NGAL can be measured with adequate precision and sensitivity on
      automated biochemistry analyzers and its measurement could easily be added to a
      standard panel to screen kidney diseases.

PMID- 26297120
TI  - Antimicrobial de-escalation in septic cancer patients: is it safe to back down?

PMID- 26297119
TI  - Our paper 20 years later: from acute renal failure to acute kidney injury--the
      metamorphosis of a syndrome.
AB  - PURPOSE: More than 20 years ago we reported an analysis of a case series of
      elderly critically ill patients with acute kidney injury (AKI)--then termed acute
      renal failure. At that time, AKI was regarded as a "simple" complication, but has
      since undergone a fundamental change and actually has become one of the central
      syndromes in the critically ill patient. METHODS: We have analyzed elderly
      patients above 65 years of age with an AKI defined as serum creatinine above 3
      mg/dl corresponding to modern KDIGO stage 3, most of them requiring renal
      replacement therapy (RRT). Using an extremely complete data set the diagnosis
      differentiated the underlying disease entity, the dominant cause of AKI, acute
      and chronic risk factors (comorbidities). Special aspects such as severity of
      disease, early AKI at admission versus late AKI, early versus later start of RRT,
      AKI not treated by RRT in spite of indication for RRT, various measures of short
      term and long-term prognosis, renal outcome, patients dying with resolved AKI,
      and causes of death were evaluated. RESULTS: Crude mortality was 61% which
      corresponds to modern studies with gross variation among the different subgroups.
      Age per se was not a determinant of survival either within the group of elderly
      patients or as compared to younger age groups. Despite an increase in mean age
      and disease severity during the observation period prognosis improved. A total of
      17% of patients developed a chronic kidney disease. Long-term survival as
      compared to the general population was low. CONCLUSIONS: A look back at the last
      two decades illustrates a remarkable evolution or rather metamorphosis of a
      syndrome. AKI has evolved as a central syndrome in intensive care patients, a
      systemic disease process associated with multiple systemic sequels and extra
      renal organ injury and exerting a pronounced effect on the course of disease and
      short- and long-term prognosis not only of the patient but also of the kidney.
      Moreover, the "non-renal-naive" elderly patient with multiple comorbidities has
      become the most frequent ICU patient in industrialized nations.

PMID- 26297121
TI  - The combined use of pumpless extracorporeal lung assist and continuous
      arteriovenous hemofiltration with citrate anticoagulation in polytrauma patients.

PMID- 26297122
TI  - Studies on the regulatory effect of Peony-Glycyrrhiza Decoction on prolactin
      hyperactivity and underlying mechanism in hyperprolactinemia rat model.
AB  - Clinical trials have demonstrated the beneficial effects of Peony-Glycyrrhiza
      Decoction (PGD) in alleviating antipsychotic-induced hyperprolactinemia
      (hyperPRL) in schizophrenic patients. In previous experiment, PGD suppressed
      prolactin (PRL) level in MMQ cells, involving modulating the expression of D2
      receptor (DRD2) and dopamine transporter (DAT). In the present study, hyperPRL
      female rat model induced by dopamine blocker metoclopramide (MCP) was applied to
      further confirm the anti-hyperpPRL activity of PGD and underlying mechanism. In
      MCP-induced hyperPRL rats, the elevated serum PRL level was significantly
      suppressed by either PGD (2.5-10 g/kg) or bromocriptine (BMT) (0.6 mg/kg)
      administration for 14 days. However, in MCP-induced rats, only PGD restored the
      under-expressed serum progesterone (P) to control level. Both PGD and BMT
      administration restore the under-expression of DRD2, DAT and TH resulted from MCP
      in pituitary gland and hypothalamus. Compared to untreated group, hyperPRL
      animals had a marked reduction on DRD2 and DAT expression in the arcuate nucleus.
      PGD (10 g/kg) and BMT (0.6 mg/kg) treatment significant reversed the expression
      of DRD2 and DAT. Collectively, the anti-hyperPRL activity of PGD associates with
      the modulation of dopaminergic neuronal system and the restoration of serum
      progesterone level. Our finding supports PGD as an effective agent against
      hyperPRL.

PMID- 26297123
TI  - Further evidence supporting the association of NKAPL with schizophrenia.
AB  - Schizophrenia (SZ) is a severe chronic mental disorder with complex genetic
      mechanisms. Increasing evidence implicate immune system dysfunction in the
      pathogenesis of SZ. The non-synonymous single nucleotide polymorphism (SNP)
      rs1635 in NKAPL, was identified by a genome-wide association study (GWAS) for SZ
      in Han Chinese from north China. A replication study failed to detect the
      association of rs1635 with SZ in Han Chinese from central south of China, while
      another one confirmed the positive association in Han Chinese from Taiwan. To
      further clarify these findings, we conducted a case-control association study of
      rs1635 in a cohort of Han Chinese from east China, including 1406 SZ cases and
      1136 healthy controls. We detected a positive association of rs1635 with SZ, with
      the major allele (G) of rs1635 conferring a risk for SZ (P=0.033, OR=1.14). Our
      findings add further evidence for the involvement of NKAPL polymorphisms in the
      development of SZ. 

PMID- 26297124
TI  - Combined therapy of Di-Huang-Yi-Zhi with Donepezil in patients with Parkinson's
      disease dementia.
AB  - Here we conducted a randomized and double-blind study attempting to explore the
      safety and efficacy of combined therapy of Di-Huang-Yi-Zhi (DHYZ) with donepezil
      in treating Parkinson's disease dementia (PDD). Sixty PDD patients were included
      and randomly divided into control group and DHYZ group. All patients were given
      donepezil (5 mg last for a month, then 10 mg for the rest months, once daily),
      while patients in DHYZ group were additionally administrated with DHYZ (150 ml,
      twice daily). The measurement subjects included mini-mental state examination
      (MMSE), Montreal cognitive assessment (MoCA), Alzheimer's Disease Assessment
      Scale-Cognitive Subscale (ADAS-Cog), the Barthel Index for activities of daily
      living (ADL) and Traditional Chinese medical (TCM) symptoms before and after
      treatment in this study. The whole study lasted for six months. Significant
      differences were observed on MMSE, MoCA, ADAS-Cog, ADL and TCM in both control
      and DHYZ group (P<0.05 or P<0.01) before and after drug treatment. Furthermore,
      there were more obvious changes of MMSE, MoCA, ADAS-Cog, ADL and TCM scores
      compared the DHYZ group with the control group (P<0.01) which suggested the DHYZ
      group showed a more effective improvement on cognition, behavior as well global
      function. In conclusion, the combined therapy of DHYZ with donepezil showed a
      more effective improvement in PDD and the underlying mechanism may be related to
      the synergic amelioration of cholinergic system between them.

PMID- 26297125
TI  - Reduction of viral load in whitefly (Bemisia tabaci Gen.) feeding on RNAi
      mediated bean golden mosaic virus resistant transgenic bean plants.
AB  - The RNAi concept was explored to silence the rep gene from the bean golden mosaic
      virus (BGMV) and a genetically modified (GM) bean immune to the virus was
      previously generated. We investigated if BGMV-viruliferous whiteflies would
      reduce viral amount after feeding on GM plants. BGMV DNA amount was significantly
      reduced in whiteflies feeding in GM-plants (compared with insects feeding on non
      GM plants) for a period of 4 and 8 days in 52% and 84% respectively. 

PMID- 26297126
TI  - Medical leech therapy in plastic reconstructive surgery.
AB  - The use of Hirudo medicinalis in clinical practice has increased in recent years.
      The primary indication in plastic surgery has traditionally been venous
      congestion. However, other reported clinical applications were in varicose veins,
      thrombophlebitis, and osteoarthritis. In this review, we summarize recent data
      elucidating the role that medicinal leeches play in the field of plastic surgery.

PMID- 26297127
TI  - Whole glucan particles as a vaccine against systemic coccidioidomycosis.
AB  - We reported previously that yeast-derived whole glucan particles (WGPs), with or
      without conjugation to BSA, used as a vaccine protected against systemic
      aspergillosis in mice. Here, we examined their utility as a potential vaccine
      against coccidioidomycosis. WGPs were prepared from Saccharomyces cerevisiae;
      conjugation with BSA (WGP-BSA) was done using 1-cyano-4-dimethylaminopyridinium
      tetrafluoroborate-mediated conjugation. Heat-killed S. cerevisiae (HKY) was used
      as a positive-control vaccine. CD-1 mice were vaccinated with WGPs or WGP-BSA,
      HKY or PBS once weekly, beginning 21 days prior to infection. Mice were infected
      intravenously with arthroconidia of Coccidioides posadasii. In the low-mortality
      study, 50 % of PBS-treated controls died. Only WGP-BSA at 0.6 mg per dose induced
      significant protection compared with PBS treatment. All surviving mice were
      infected in all three organs examined. Those given WGP-BSA at 0.6 mg per dose had
      fewer c.f.u. in liver and lungs (P = 0.04), and those given WGPs at 6 mg per dose
      had fewer in lungs (P < 0.02), compared with PBS. In the high-mortality study, 90
      % of PBS mice died. Vaccination with HKY, and WGPs or WGP-BSA at 6 or 12 mg per
      dose significantly prolonged survival (P <= 0.05). No surviving mice were free of
      infection. HKY and WGP-BSA at 12 mg per dose reduced c.f.u. in the liver and
      lungs (P < 0.05) and WGP-BSA at 6 mg per dose reduced c.f.u. in the lungs (P <
      0.05); unconjugated WGPs did not reduce infection. WGPs or WGP-BSA acted as a
      vaccine that protected against mortality caused by coccidioidomycosis. Thus, WGP
      protection against coccidioidomycosis and aspergillosis provides the basis for
      development of a pan-fungal vaccine. 

PMID- 26297128
TI  - Do male secondary sexual characters correlate with testis size and sperm length
      in the small hairy maggot blowfly?
AB  - The phenotype-linked fertility hypothesis proposes that secondary sexual
      characters (SSCs) advertise a male's fertility to prospective mates. However,
      findings from empirical studies attempting to test this hypothesis are often
      ambivalent or even contradictory, and few studies have simultaneously evaluated
      how both morphological and behavioural SSCs relate to ejaculate characteristics.
      Males of the small hairy maggot blowfly, Chrysomya varipes, possess conspicuous
      foreleg ornaments and display highly stereotyped courtship behaviour. These
      traits are favoured by females during pre-copulatory mate choice, but it remains
      unknown whether they correlate with post-copulatory traits expected to influence
      male fertility. The aim of this study was to investigate whether male courtship
      and ornamentation correlate with testis size and sperm length in C. varipes. We
      found that males investing more in courtship had bigger testes, and males with
      more extensive foreleg ornamentation released sperm with longer tails. Based on
      the assumption that larger testes enable males to produce more sperm, and that
      sperm with longer tails have greater propulsive force, our findings suggest that
      more vigorous and more ornamented males may be more fertile. These findings lend
      support to the phenotype-linked fertility hypothesis. However, a complete test of
      this hypothesis will require evaluating whether testis size and sperm length
      influence male fertilisation ability, as well as female fecundity and/or
      fertility. 

PMID- 26297129
TI  - Investigation of the oral status and microorganisms in children with
      phenylketonuria and type 1 diabetes.
AB  - OBJECTIVE: The aim of this study was to investigate the oral parameters that
      influence the caries risk and risk of developing periodontal disease in children
      with phenylketonuria (PKU) and type 1 diabetes compared to healthy children.
      MATERIAL AND METHODS: Two hundred and thirty-eight children between the ages of 3
      and 18 years were recruited in the PKU, diabetes and healthy group. The decayed,
      missing and filled surfaces (dmfs/DMFS) index, papillary bleeding index (PBI) and
      the Silness & Loe Index were assessed. Quantitative real-time polymerase chain
      reaction (PCR) was used for the detection of Streptococcus mutans (Sm),
      Lactobacillus casei (Lca), Lactobacillus species (Lac), Aggregatibacter
      actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg) and Tannerella
      forsythensis (Tf). RESULTS: A statistically significant difference in the dmfs
      index value was found between the three groups. The mean dmfs index value for the
      PKU children (4.18) was found to be relatively high. Comparing the three groups,
      diabetics showed statistically significant higher values for the Silness and Loe
      Index. Comparing the diabetics to just the healthy children, the diabetics
      revealed a small statistically significant difference in the PBI score. A
      statistically significant difference was found between Lac, Lca and Pg in the
      three groups. Counts of Lac were the lowest in the PKU children. The diabetics
      showed the highest counts of Lca but lowest for Pg. CONCLUSIONS: Comparing the
      three groups, children with PKU revealed a higher caries experience in their
      primary dentition. While the diabetic children showed a lower one in their
      primary dentition, they were found to possess a slightly higher risk of
      developing periodontal disease. CLINICAL RELEVANCE: It is proposed that both
      groups of child patients be encouraged to seek early dental advice and be
      incorporated in a meticulous prevention programme.

PMID- 26297131
TI  - Streptomyces gilvifuscus sp. nov., an actinomycete that produces antibacterial
      compounds isolated from soil.
AB  - This study describes a novel actinomycete, designated T113T, which was isolated
      from forest soil in Pyeongchang-gun, Republic of Korea, and is an aerobic, Gram
      stain-positive actinobacterium that forms flexibilis chains of smooth, elliptical
      or short rod-shaped spores. The results of 16S rRNA sequence analysis indicated
      that strain T113T exhibited high levels of similarity to previously characterized
      species of the genus Streptomyces (98.19-98.89 %, respectively). However, the
      results of phylogenetic and DNA-DNA hybridization analyses confirmed that the
      organism represented a novel member of the genus Streptomyces. Furthermore, using
      chemotaxonomic and phenotypic analyses it was demonstrated that the strain
      exhibited characteristics similar to those of other members of the genus
      Streptomyces. The primary cellular fatty acids expressed by this strain included
      anteiso-C15 : 0, anteiso-C17 : 0, iso-C15 : 0 and iso-C16 : 0. While
      diphosphatidylglycerol and phosphatidylethanolamine were the predominant lipids
      expressed by strain T113T, moderate amounts of phosphatidylinositol and
      phosphatidylinositol mannoside were also detected. Whole-cell hydrolysates
      contained glucose and ribose, and the predominant menaquinone detected was MK-9
      (H6); however, moderate amounts of MK-9 (H8) and trace amounts of MK-10 (H2) and
      MK-10 (H4) were also detected. We therefore propose that strain T113T be
      considered as representing a novel species of the genus Streptomyces and propose
      the name Streptomyces gilvifuscus sp. nov. for this species, with strain T113T (
      = KEMB 9005-213T = KACC 18248T = NBRC 110904T) being the type strain.

PMID- 26297130
TI  - Erlotinib and gefitinib responsiveness in head and neck cancer cell lines--a
      comparing analysis with cetuximab.
AB  - OBJECTIVE: The objective of this study is to examine the efficacy of erlotinib
      and gefitinib with respect to epidermal growth factor (EGF) and cetuximab
      response in head and neck cancer cell lines. MATERIALS AND METHODS: Five human
      head and neck carcinoma cell lines were treated with EGF, cetuximab, erlotinib,
      and gefitinib, and the effects were measured with a crystal violet assay. The
      efficacies of cetuximab, erlotinib, and gefitinib in clinically relevant
      concentrations were statistically analyzed. The expression of the epidermal
      growth factor receptor (EGFR) and phosphorylation patterns were detected with
      fluorescence-activated cell sorting (FACS) analysis and western blot analysis.
      The endogenous production of EGF by the cells was detected with an enzyme-linked
      immunosorbent assay. Finally, EGFR, KRAS, BRAF, and PI3K mutation analyses were
      performed. RESULTS: All of the cell lines had a poor or no response to EGF but
      exhibited distinct EGFR phosphorylation and EGFR expression. Compared to
      cetuximab, erlotinib and gefitinib demonstrated a greater impact on the majority
      of the cell lines. The only cell line that showed a concentration-dependent
      behavior toward EGF and strong EGFR phosphorylation was entirely resistant to
      cetuximab, erlotinib, and gefitinib. The production of EGF in all cell lines was
      very low. Mutational analysis of all cell lines revealed wild-type EGFR, KRAS,
      BRAF, and PI3K. CONCLUSIONS: The prediction of anti-EGFR treatment cannot be
      based on responsiveness to EGF or EGFR activation. CLINICAL RELEVANCE: Erlotinib
      and gefitinib show good response in EGF-independent cell lines and might be
      useful drugs in tumors that are less responsive to cetuximab.

PMID- 26297132
TI  - Fecal Recovery of Ingested Cellular DNA: Implications for Noninvasive Detection
      of Upper Gastrointestinal Neoplasms.
AB  - BACKGROUND: Stool DNA testing represents a potential noninvasive approach to
      detect upper gastrointestinal (UGI) neoplasms. However, little is known about
      fecal recovery efficiency of DNA exfoliated from UGI tumors. AIMS: The purpose of
      this study was to establish a human ingestion model that quantitatively
      approximates daily cellular shedding from UGI neoplasms and to estimate fecal DNA
      marker recovery rates. METHODS: Healthy volunteers (n = 10) ingested two
      scheduled doses of raw salmon, 0.3 and 30 g, simulating the mass exfoliated daily
      from 1 to 4.5 cm lesions. To approach a steady-state, each dose was ingested over
      three consecutive days in randomized order. Following defecation of an indicator
      dye ingested with test meals, stools were collected over 48 h. Ingested salmon
      DNA was captured from stools using probes targeting pathognomonic Salmonidae
      sequences (SlmII). Captured DNA was quantified using PCR primers to generate 178,
      138, 88 and 55 bp amplicons. RESULTS: SlmII sequences were recovered from all
      stools following salmon ingestion; recovery was proportional to amount ingested
      (p = 0.004). Fecal recovery of ingested salmon varied inversely with amplicon
      size targeted; mean recovery rates of SlmII were 0.49, 0.91, 3.63, and 7.31
      copies per 100,000 copies ingested for 178, 134, 88, and 55 bp amplicons,
      respectively (p < 0.0001). Longer oro-anal transit was associated with reduced
      recovery. CONCLUSIONS: While recovery efficiencies are low, ingested cellular DNA
      simulating daily amounts shed from UGI tumors can readily be detected in stool.
      Assay of shorter-fragment analyte increases recovery. This ingestion model has
      potential value in studying the effects of perturbations relevant to the fecal
      recovery of DNA exfoliated from UGI tumors.

PMID- 26297133
TI  - Risk Factors Associated with Rebleeding in Patients with High Risk Peptic Ulcer
      Bleeding: Focusing on the Role of Second Look Endoscopy.
AB  - BACKGROUND: Re-bleeding after initial hemostasis in peptic ulcer bleeding can be
      life threatening. Identification of factors associated with re-bleeding is
      important. The aims of this study were to determine incidence of rebleeding in
      patients with high risk peptic ulcer bleeding and to evaluate factors associated
      with rebleeding. METHODS: Among patients diagnosed as upper gastrointestinal
      hemorrhage at seven hospitals in Daegu-Gyeongbuk, and one hospital in Gyeongnam,
      South Korea, from Feb 2011 to Dec 2013, 699 patients diagnosed as high risk
      peptic ulcer bleeding with Forrest classification above llb were included. The
      data were obtained in a prospective manner. RESULTS: Among 699 patients, re
      bleeding occurred in 64 (9.2 %) patients. Second look endoscopy was significantly
      more performed in the non-rebleeding group than the rebleeding group (81.8 vs
      62.5 %, p < 0.001). In multivariate analysis, use of non-steroidal anti
      inflammatory agents, larger transfusion volume (>=5 units), and non-performance
      of second look endoscopy were found as risk factors for rebleeding in high risk
      peptic ulcer bleeding. CONCLUSION: In our study, rebleeding was observed in 9.2 %
      of patients with high risk peptic ulcer bleeding. Performance of second look
      endoscopy seems to lower the risk of rebleeding in high risk peptic ulcer
      bleeding patients and caution should be paid to patients receiving high volume
      transfusion and on medication with NSAIDs.

PMID- 26297134
TI  - Algoriphagus aestuarii sp. nov., a member of the Cyclobacteriaceae isolated from
      a tidal-flat sediment of the Yellow Sea in Korea.
AB  - A Gram-strain-negative, coccoid or oval-shaped, non-motile bacterial strain,
      designated MDM-1T, was isolated from a tidal-flat sediment on the Korean
      peninsula. Strain MDM-1T was found to grow optimally at pH 7.0-8.0, at 30 
      degrees C and in the presence of 2-3 % (w/v) NaCl. A neighbour-joining
      phylogenetic tree based on 16S rRNA gene sequences showed that strain MDM-1T
      falls within the clade comprising species of the genus Algoriphagus, clustering
      with the type strains of Algoriphagus halophilus, A. lutimaris, A. chungangensis
      and A. machipongonensis, with which it exhibited 97.2-98.5 % 16S rRNA gene
      sequence similarity. Sequence similarities to the type strains of the other
      recognized species of the genus Algoriphagus were 92.8-97.6 %. Strain MDM-1T was
      found to contain MK-7 as the predominant menaquinone and iso-C15 : 0 and summed
      feature 3 (C16 : 1omega6c and/or C16 : 1omega7c) as the major fatty acids. The
      major polar lipids were identified as phosphatidylcholine,
      phosphatidylethanolamine and two unidentified lipids. The DNA G+C content of
      strain MDM-1T was determined to be 42.7 mol% and the mean DNA-DNA relatedness
      with A. halophilus KCTC 12051T, A. lutimaris S1-3T, A. chungangensis KCTC 23759T,
      A. machipongonensis DSM 24695T and A. ratkowskyi CIP 107452T was 19.7-5.2 %.
      Differential phenotypic properties, together with the phylogenetic and genetic
      distinctiveness, revealed that strain MDM-1T is distinguishable from recognized
      species of the genus Algoriphagus. On the basis of the data presented, strain MDM
      1T is proposed to represent a novel species of the genus Algoriphagus, for which
      the name Algoriphagus aestuarii sp. nov. is proposed. The type strain is MDM-1T (
      = KCTC 42199T = NBRC 110552T). 

PMID- 26297135
TI  - Physicians' Counseling of Adolescents Regarding E-Cigarette Use.
AB  - PURPOSE: Electronic cigarette (e-cigarette) use now surpasses the use of
      conventional cigarettes among U.S. adolescents. Given the important role of
      physicians in preventing adolescent risk behaviors, we sought to understand how
      physicians communicate about e-cigarettes when counseling adolescent patients and
      their parents. We also explored physicians' support for regulations aimed at
      discouraging adolescents' e-cigarette use. METHODS: A national U.S. sample of 776
      pediatricians and family medicine physicians who provide primary care to
      adolescent patients completed an online survey in Spring 2014. RESULTS: Many
      physicians (41%) would, if asked, tell their patients that e-cigarettes are less
      harmful than cigarettes, and a substantial minority (24%) would recommend e
      cigarettes to adolescents for smoking cessation. Most physicians reported
      routinely screening adolescent patients for cigarette smoking but few routinely
      screened for e-cigarette use (86% vs. 14%; p < .001). Routine counseling was
      similarly more common for avoiding cigarette smoking than for avoiding e
      cigarette use (79% vs. 18%; p < .001). Support for government regulation of e
      cigarettes was high, with 91% of physicians endorsing policies that prevent
      minors from buying e-cigarettes. CONCLUSIONS: Physicians infrequently screen or
      counsel their adolescent patients about e-cigarette use, although e-cigarettes
      often come up during visits. Additional efforts by physicians could help prevent
      future use by adolescents. Recommending e-cigarettes as a smoking cessation aid
      to adolescent patients is inadvisable given the lack of evidence for efficacy in
      that population. As federal regulation of e-cigarettes remains in limbo,
      pediatricians and family medicine physicians can offer a powerful voice for
      informing regulations aimed at reducing use by adolescents.

PMID- 26297136
TI  - A preliminary study on surgical navigation for epiduroscopic laser neural
      decompression.
AB  - Epiduroscopic laser neural decompression is an emerging therapeutic modality to
      treat lumbar spine pathologies including chronic low back pain, spinal stenosis,
      and disk herniation via catheter insertion followed by laser ablation of the
      lesion. Despite the efficacy of epiduroscopic laser neural decompression,
      excessive radiation doses due to fluoroscopy during epiduroscopic laser neural
      decompression have limited its widespread application. To address the issue, we
      propose a surgical navigation system to assist in epiduroscopic laser neural
      decompression procedures using radiation-free image guidance. An electromagnetic
      tracking system was used as the basic modality to track the internal location of
      the surgical instrument with respect to the patient body. Patient-to-image
      registration was carried out using the point-based registration method to
      determine the transformation between the coordinate system of the patient and
      that of the medical images. We applied the proposed system in epiduroscopic laser
      neural decompression procedures to assess its effectiveness, and the outcomes
      confirmed its clinical feasibility. To the best of our knowledge, this is a
      report on the first surgical navigation applied for epiduroscopic laser neural
      decompression procedure. 

PMID- 26297137
TI  - Mature Surfactant Protein-B Expression by Immunohistochemistry as a Marker for
      Surfactant System Development in the Fetal Sheep Lung.
AB  - Evaluation of the number of type II alveolar epithelial cells (AECs) is an
      important measure of the lung's ability to produce surfactant.
      Immunohistochemical staining of these cells in lung tissue commonly uses
      antibodies directed against mature surfactant protein (SP)-C, which is regarded
      as a reliable SP marker of type II AECs in rodents. There has been no study
      demonstrating reliable markers for surfactant system maturation by
      immunohistochemistry in the fetal sheep lung despite being widely used as a model
      to study lung development. Here we examine staining of a panel of surfactant pro
      proteins (pro-SP-B and pro-SP-C) and mature proteins (SP-B and SP-C) in the fetal
      sheep lung during late gestation in the saccular/alveolar phase of development
      (120, 130, and 140 days), with term being 150 +/- 3 days, to identify the most
      reliable marker of surfactant producing cells in this species. Results from this
      study indicate that during late gestation, use of anti-SP-B antibodies in the
      sheep lung yields significantly higher cell counts in the alveolar epithelium
      than SP-C antibodies. Furthermore, this study highlights that mature SP-B
      antibodies are more reliable markers than SP-C antibodies to evaluate surfactant
      maturation in the fetal sheep lung by immunohistochemistry.

PMID- 26297138
TI  - Drought Induces Distinct Growth Response, Protection, and Recovery Mechanisms in
      the Maize Leaf Growth Zone.
AB  - Drought is the most important crop yield-limiting factor, and detailed knowledge
      of its impact on plant growth regulation is crucial. The maize (Zea mays) leaf
      growth zone offers unique possibilities for studying the spatiotemporal
      regulation of developmental processes by transcriptional analyses and methods
      that require more material, such as metabolite and enzyme activity measurements.
      By means of a kinematic analysis, we show that drought inhibits maize leaf growth
      by inhibiting cell division in the meristem and cell expansion in the elongation
      zone. Through a microarray study, we observed the down-regulation of 32 of the 54
      cell cycle genes, providing a basis for the inhibited cell division. We also
      found evidence for an up-regulation of the photosynthetic machinery and the
      antioxidant and redox systems. This was confirmed by increased chlorophyll
      content in mature cells and increased activity of antioxidant enzymes and
      metabolite levels across the growth zone, respectively. We demonstrate the
      functional significance of the identified transcriptional reprogramming by
      showing that increasing the antioxidant capacity in the proliferation zone, by
      overexpression of the Arabidopsis (Arabidopsis thaliana) iron-superoxide
      dismutase gene, increases leaf growth rate by stimulating cell division. We also
      show that the increased photosynthetic capacity leads to enhanced photosynthesis
      upon rewatering, facilitating the often-observed growth compensation. 

PMID- 26297139
TI  - Overexpression of BAX INHIBITOR-1 Links Plasma Membrane Microdomain Proteins to
      Stress.
AB  - BAX INHIBITOR-1 (BI-1) is a cell death suppressor widely conserved in plants and
      animals. Overexpression of BI-1 enhances tolerance to stress-induced cell death
      in plant cells, although the molecular mechanism behind this enhancement is
      unclear. We recently found that Arabidopsis (Arabidopsis thaliana) BI-1 is
      involved in the metabolism of sphingolipids, such as the synthesis of 2-hydroxy
      fatty acids, suggesting the involvement of sphingolipids in the cell death
      regulatory mechanism downstream of BI-1. Here, we show that BI-1 affects cell
      death-associated components localized in sphingolipid-enriched microdomains of
      the plasma membrane in rice (Oryza sativa) cells. The amount of 2-hydroxy fatty
      acid-containing glucosylceramide increased in the detergent-resistant membrane
      (DRM; a biochemical counterpart of plasma membrane microdomains) fraction
      obtained from BI-1-overexpressing rice cells. Comparative proteomics analysis
      showed quantitative changes of DRM proteins in BI-1-overexpressing cells. In
      particular, the protein abundance of FLOTILLIN HOMOLOG (FLOT) and HYPERSENSITIVE
      INDUCED REACTION PROTEIN3 (HIR3) markedly decreased in DRM of BI-1-overexpressing
      cells. Loss-of-function analysis demonstrated that FLOT and HIR3 are required for
      cell death by oxidative stress and salicylic acid, suggesting that the decreased
      levels of these proteins directly contribute to the stress-tolerant phenotypes in
      BI-1-overexpressing rice cells. These findings provide a novel biological
      implication of plant membrane microdomains in stress-induced cell death, which is
      negatively modulated by BI-1 overexpression via decreasing the abundance of a set
      of key proteins involved in cell death. 

PMID- 26297140
TI  - Isolation and Characterization of O-methyltransferases Involved in the
      Biosynthesis of Glaucine in Glaucium flavum.
AB  - Transcriptome resources for the medicinal plant Glaucium flavum were searched for
      orthologs showing identity with characterized O-methyltransferases (OMTs)
      involved in benzylisoquinoline alkaloid biosynthesis. Seven recombinant proteins
      were functionally tested using the signature alkaloid substrates for six OMTs:
      norlaudanosoline 6-OMT, 6-O-methyllaudanosoline 4'-OMT, reticuline 7-OMT,
      norreticuline 7-OMT, scoulerine 9-OMT, and tetrahydrocolumbamine OMT. A notable
      alkaloid in yellow horned poppy (G. flavum [GFL]) is the aporphine alkaloid
      glaucine, which displays C8-C6' coupling and four O-methyl groups at C6, C7, C3',
      and C4' as numbered on the 1-benzylisoquinoline scaffold. Three recombinant
      enzymes accepted 1-benzylisoquinolines with differential substrate and
      regiospecificity. GFLOMT2 displayed the highest amino acid sequence identity with
      norlaudanosoline 6-OMT, showed a preference for the 6-O-methylation of
      norlaudanosoline, and O-methylated the 3' and 4' hydroxyl groups of certain
      alkaloids. GFLOMT1 showed the highest sequence identity with 6-O
      methyllaudanosoline 4'OMT and catalyzed the 6-O-methylation of norlaudanosoline,
      but more efficiently 4'-O-methylated the GFLOMT2 reaction product 6-O
      methylnorlaudanosoline and its N-methylated derivative 6-O-methyllaudanosoline.
      GFLOMT1 also effectively 3'-O-methylated both reticuline and norreticuline.
      GFLOMT6 was most similar to scoulerine 9-OMT and efficiently catalyzed both 3'-
      and 7'-O-methylations of several 1-benzylisoquinolines, with a preference for N
      methylated substrates. All active enzymes accepted scoulerine and
      tetrahydrocolumbamine. Exogenous norlaudanosoline was converted to tetra-O
      methylated laudanosine using combinations of Escherichia coli producing (1)
      GFLOMT1, (2) either GFLOMT2 or GFLOMT6, and (3) coclaurine N-methyltransferase
      from Coptis japonica. Expression profiles of GFLOMT1, GFLOMT2, and GFLOMT6 in
      different plant organs were in agreement with the O-methylation patterns of
      alkaloids in G. flavum determined by high-resolution, Fourier-transform mass
      spectrometry. 

PMID- 26297143
TI  - Bizionia fulviae sp. nov., isolated from the gut of an egg cockle, Fulvia mutica.
AB  - A novel Gram-staining-negative, non-spore-forming, non-flagellated, non-motile,
      aerobic, saffron-coloured, rod-shaped bacterium that did not produce flexirubin
      type pigments was designated strain EM7(T) and was distinct from other members of
      the genus Bizionia by produce carotenoid-type pigments and being able to grow
      independently of NaCl. Strain EM7(T) was isolated from the intestinal tract of an
      egg cockle, Fulvia mutica, which had been collected from the West Sea in Korea.
      Phylogenetic analysis based on the 16S rRNA gene sequence showed that strain
      EM7(T) belonged to the genus Bizionia, and showed sequence similarity to Bizionia
      paragorgiae KMM 6029(T) (97.9%) and Bizionia saleffrena HFD(T) (97.73%). Growth
      occurred on marine agar 2216 at 0-25  degrees C (optimum, 20  degrees C) and at
      pH 6-9 (optimum, pH 7). Growth occurred in the presence of 0-10% (w/v) NaCl
      (optimum, 2%, w/v, NaCl). The major cellular fatty acids were anteiso-C15 : 0,
      iso-C15 : 0, iso-C15 : 1 G, summed feature 3 (C16 : 1omega7c and/or C16 :
      1omega6c), iso-C17 : 0 3-OH and iso-C16 : 0 3-OH. The major respiratory quinone
      was menaquinone MK-6. The polar lipids of strain EM7(T) comprised
      phosphatidylethanolamine, three unidentified aminolipids, an unidentified
      aminophospholipid and two unidentified lipids. The genomic DNA G+C content was
      34.8 mol%. Bizionia paragorgiae KMM 6029(T) and Bizionia saleffrena HFD(T) to
      Bizionia paragorgiae KCTC 12304(T) and Bizionia saleffrena CIP 108534(T),
      respectively. Thus, it is proposed that the isolate represents a novel species,
      Bizionia fulviae sp. nov., with strain EM7(T) ( = KACC 18255(T) = JCM 30417(T))
      as the type strain.

PMID- 26297141
TI  - A CRISPR/Cas9 Toolbox for Multiplexed Plant Genome Editing and Transcriptional
      Regulation.
AB  - The relative ease, speed, and biological scope of clustered regularly interspaced
      short palindromic repeats (CRISPR)/CRISPR-associated Protein9 (Cas9)-based
      reagents for genomic manipulations are revolutionizing virtually all areas of
      molecular biosciences, including functional genomics, genetics, applied
      biomedical research, and agricultural biotechnology. In plant systems, however, a
      number of hurdles currently exist that limit this technology from reaching its
      full potential. For example, significant plant molecular biology expertise and
      effort is still required to generate functional expression constructs that allow
      simultaneous editing, and especially transcriptional regulation, of multiple
      different genomic loci or multiplexing, which is a significant advantage of
      CRISPR/Cas9 versus other genome-editing systems. To streamline and facilitate
      rapid and wide-scale use of CRISPR/Cas9-based technologies for plant research, we
      developed and implemented a comprehensive molecular toolbox for multifaceted
      CRISPR/Cas9 applications in plants. This toolbox provides researchers with a
      protocol and reagents to quickly and efficiently assemble functional CRISPR/Cas9
      transfer DNA constructs for monocots and dicots using Golden Gate and Gateway
      cloning methods. It comes with a full suite of capabilities, including
      multiplexed gene editing and transcriptional activation or repression of plant
      endogenous genes. We report the functionality and effectiveness of this toolbox
      in model plants such as tobacco (Nicotiana benthamiana), Arabidopsis (Arabidopsis
      thaliana), and rice (Oryza sativa), demonstrating its utility for basic and
      applied plant research. 

PMID- 26297142
TI  - Intermittent high dose proton pump inhibitor enhances the antitumor effects of
      chemotherapy in metastatic breast cancer.
AB  - BACKGROUND: Acidity is a hallmark of malignant tumor, representing a very
      efficient mechanism of chemoresistance. Proton pump inhibitors (PPI) at high
      dosage have been shown to sensitize chemoresistant human tumor cells and tumors
      to cytotoxic molecules. The aim of this pilot study was to investigate the
      efficacy of PPI in improving the clinical outcome of docetaxel + cisplatin
      regimen in patients with metastatic breast cancer (MBC). METHODS: Patients
      enrolled were randomly assigned to three arms: Arm A, docetaxel 75 mg/m(2)
      followed by cisplatin 75 mg/m(2) on d4, repeated every 21 days with a maximum of
      6 cycles; Arm B, the same chemotherapy preceded by three days esomeprazole (ESOM)
      80 mg p.o. bid, beginning on d1 repeated weekly. Weekly intermittent
      administration of ESOM (3 days on 4 days off) was maintained up to maximum 66
      weeks; Arm C, the same as Arm B with the only difference being dose of ESOM at
      100 mg p.o. bid. The primary endpoint was response rate. RESULTS: Ninety-four
      patients were randomly assigned and underwent at least one injection of
      chemotherapy. Response rates for arm A, B and C were 46.9, 71.0, and 64.5 %,
      respectively. Median TTP for arm A (n = 32), B (n = 31), C (n = 31) were 8.7,
      9.4, and 9.7 months, respectively. A significant difference was observed between
      patients who had taken PPI and who not with ORR (67.7 % vs. 46.9 %, p = 0.049)
      and median TTP (9.7 months vs. 8.7 months, p = 0.045) [corrected]. Exploratory
      analysis showed that among 15 patients with triple negative breast cancer (TNBC),
      this difference was bigger with median TTP of 10.7 and 5.8 months, respectively
      (p = 0.011). PPI combination showed a marked effect on OS as well, while with a
      borderline significance (29.9 vs. 19.2 months, p = 0.090). No additional toxicity
      was observed with PPI. CONCLUSIONS: The results of this pilot clinical trial
      showed that intermittent high dose PPI enhance the antitumor effects of
      chemotherapy in MBC patients without evidence of additional toxicity, which
      requires urgent validation in a multicenter, randomized, phase III trial. TRIAL
      REGISTRATION: Clinicaltrials.gov identifier: NCT01069081 .

PMID- 26297144
TI  - Decreased heart rate variability responses during early postoperative
      mobilization--an observational study.
AB  - BACKGROUND: Intact orthostatic blood pressure regulation is essential for early
      mobilization after surgery. However, postoperative orthostatic hypotension and
      intolerance (OI) may delay early ambulation. The mechanisms of postoperative OI
      include impaired vasopressor responses relating to postoperative autonomic
      dysfunction. Thus, based on a previous study on haemodynamic responses during
      mobilization before and after elective total hip arthroplasty (THA), we performed
      secondary analyses of heart rate variability (HRV) and aimed to identify possible
      abnormal postoperative autonomic responses in relation to postural change.
      METHODS: A standardized mobilization protocol before, 6 and 24 h after surgery
      was performed in 23 patients scheduled for elective THA. Beat-to-beat arterial
      blood pressure was measured by photoplethysmography and HRV was derived from
      pulse wave interbeat intervals and analysed in the time and frequency domain as
      well as by non-linear analysis using sample entropy RESULTS: Before surgery,
      arterial pressures and HR increased upon standing, while HRV low (LF) and high
      frequency (HF) components remained unchanged. At 6 and 24 h after surgery,
      resting total HRV power, sample entropy and postural responses in arterial
      pressures decreased compared to preoperative conditions. During standing HF
      variation increased by 16.7 (95 % CI 8.0-25.0) normalized units (nu) at 6 h and
      10.7 (2.0-19.4) nu at 24 h compared to the preoperative evaluation. At 24 h the
      LF/HF ratio decreased from 1.8 (1.2-2.6) nu when supine to 1.2 (0.8-1.8) nu when
      standing. CONCLUSIONS: This study observed postoperative autonomic cardiovascular
      dysregulation that may contribute to limited HRV responses during early
      postoperative mobilization. TRIAL REGISTRATION: ClinicalTrials.gov NCT01089946.

PMID- 26297145
TI  - Identification of strains Bacillus aerophilus MTCC 7304T as Bacillus altitudinis
      and Bacillus stratosphericus MTCC 7305T as a Proteus sp. and the status of the
      species Bacillus aeriusShivaji et al. 2006. Request for an Opinion.
AB  - On the basis of 16S rRNA, rpoB, gyrB and pycA gene sequence analyses,
      characterization of biochemical features and other phenotypic traits and pulsed
      field gel electrophoresis (PFGE) fingerprinting, it was ascertained that strains
      Bacillus aerius MTCC 7303T, Bacillus aerophilus MTCC 7304(T) and Bacillus
      stratosphericus MTCC 7305(T) do not conform to the descriptions of the type
      strains of the respective species. Strains MTCC 7303(T) and MTCC 7304(T) were
      indistinguishable from Bacillus altitudinis DSM 21631(T), while strain MTCC
      7305(T) should be classified as a representative of a Proteus sp. Our attempts to
      find other deposits of the type strains of these species were unsuccessful.
      Therefore, the results support the Request for an Opinion on the status of the
      species Bacillus aerophilus and Bacillus stratosphericus by Branquinho et al.
      [Branquinho, R., Klein, G., Kampfer, P. & Peixe, L. V. (2015). Int J Syst Evol
      Microbiol 65, 1101]. It is also proposed that the Judicial Commission should
      place the name Bacillus aerius on the list of rejected names if a suitable
      replacement type strain cannot be found or a neotype is not proposed within two
      years following the publication of this Request (Rule 18c).

PMID- 26297146
TI  - RNA sequencing analysis identifies novel spliced transcripts but does not
      indicate quantitative or qualitative changes of viral transcripts during
      progression of cottontail rabbit papillomavirus-induced tumours.
AB  - Persistent infections with high-risk human papillomaviruses (HPVs) can result in
      the development of cancer of the cervix uteri and other malignancies. The
      underlying molecular mechanisms leading to the progression of HPV-induced lesions
      are, however, not well understood. Cottontail rabbit papillomavirus (CRPV)
      induces papillomas in domestic rabbits which progress at a very high rate to
      cancer. Using this model, we compared the transcriptional patterns of CRPV in
      papillomas and carcinomas by RNA sequencing (RNA-seq). The most abundant
      transcripts can encode E7, short E6 and E1^E4, followed by full-length E6, E2, E1
      and E9^E2C. In addition, we identified two rare, novel splice junctions 7810/3714
      and 1751/3065 in both papillomas and carcinomas which have been described for
      other papillomaviruses. Neither RNA-seq nor quantitative real-time PCR-based
      assays identified qualitative or quantitative changes of viral transcription
      between papillomas and carcinomas. In summary, our analyses confirmed that
      papillomaviruses have highly similar transcriptional patterns, but they do not
      suggest that changes in these patterns contribute to the progression of CRPV
      induced tumours. 

PMID- 26297147
TI  - Tenggerimyces mesophilus gen. nov., sp. nov., a member of the family
      Nocardioidaceae.
AB  - A novel aerobic actinomycete, designated strain I12A-02601T, was isolated from a
      desert soil crusts sample collected from the Shapotou region of Tengger Desert,
      north-west China. The substrate mycelia of this isolate were well-developed and
      branched, but not fragmented. The maturity aerial mycelia formed short chains of
      small, rod-shaped spores. The strain contained ll-diaminopimelic acid, dd
      diaminopimelic acid, galactose, glucose, ribose and xylose in its whole-cell
      hydrolysates. The polar lipids consisted of diphosphatidylglycerol, N
      acetylglucosamine-containing phospholipids, phosphatidylinositolmannoside and
      glycolipids. The predominant menaquinones were MK-10(H6) and MK-10(H8). The major
      fatty acids were iso-C15 : 0, anteiso-C15 : 0, C16 : 0, anteiso-C17 : 0 and iso
      C16 : 0. The G+C content of the genomic DNA was 72.2 mol%. The 16S rRNA gene
      sequences comparison showed that strain I12A-02601T was most closely related to
      members of the family Nocardioidaceae, such as Actinopolymorpha alba YIM 48868T
      (93.3 % sequence similarity), Actinopolymorpha pittospori PIP 143T (93.2 %), and
      Flindersiella endophytica EUM 378T (93.2 %). In the phylogenetic tree based on
      16S rRNA gene sequences, strain I12A-02601T formed a clade with the members of
      the genera Flindersiella, Thermasporomyces, and Actinopolymorpha in the family
      Nocardioidaceae. Combined data from this taxonomic study using a polyphasic
      approach, led to the conclusion that strain I12A-02601T represents a novel
      species of a new genus in the family Nocardioidaceae, for which the name
      Tenggerimyces mesophilus gen. nov., sp. nov. is proposed. The type strain of the
      type species is I12A-02601T ( = CPCC 203544T = DSM 45829T = NBRC 109454T).

PMID- 26297149
TI  - Zoledronic acid-induced hepatotoxicity relieved after subsequent infusions in a
      Chinese woman with glucocorticoid-induced osteoporosis.
AB  - BACKGROUND: Zoledronic acid (ZOL) is widely used for treatment of glucocorticoid
      induced osteoporosis. The most common adverse effects of ZOL treatment are post
      dose symptoms. ZOL-induced hepatotoxicity has very rarely been reported. CASE
      REPORT: Here, we described a 50-year-old Chinese woman who had vertebral
      fractures and severe back pain after glucocorticoid therapy for Behcet disease
      for 13 years. Three days after ZOL 5 mg infusion in April 2012, serum alanine
      aminotransferase (ALT), aspartate aminotransferase (AST) and gamma
      glutamyltransferase (GGT) levels increased by 7.7, 4.9 and 3.0 times,
      respectively, compared with pre-treatment values. Liver protective agents were
      administered per os. Her hepatic enzyme levels returned to nearly normal range 9
      days post-infusion. In the subsequent ZOL infusion with 1 year interval, serum
      ALT, AST and GGT levels increased slightly after the second infusion and were
      sustained to be normal after the third infusion. Her post-dose symptoms
      alleviated in the meantime. CONCLUSIONS: Hepatotoxicity due to ZOL therapy is a
      rare, but possible adverse effect which may be relieved after subsequent
      infusions.

PMID- 26297148
TI  - Dynamics of virus shedding and antibody responses in influenza A virus-infected
      feral swine.
AB  - Given their free-ranging habits, feral swine could serve as reservoirs or
      spatially dynamic 'mixing vessels' for influenza A virus (IAV). To better
      understand virus shedding patterns and antibody response dynamics in the context
      of IAV surveillance amongst feral swine, we used IAV of feral swine origin to
      perform infection experiments. The virus was highly infectious and transmissible
      in feral swine, and virus shedding patterns and antibody response dynamics were
      similar to those in domestic swine. In the virus-inoculated and sentinel groups,
      virus shedding lasted <= 6 and <= 9 days, respectively. Antibody titres in
      inoculated swine peaked at 1 : 840 on day 11 post-inoculation (p.i.), remained
      there until 21 days p.i. and dropped to < 1 : 220 at 42 days p.i. Genomic
      sequencing identified changes in wildtype (WT) viruses and isolates from sentinel
      swine, most notably an amino acid divergence in nucleoprotein position 473. Using
      data from cell culture as a benchmark, sensitivity and specificity of a matrix
      gene-based quantitative reverse transcription-PCR method using nasal swab samples
      for detection of IAV in feral swine were 78.9 and 78.1 %, respectively. Using
      data from haemagglutination inhibition assays as a benchmark, sensitivity and
      specificity of an ELISA for detection of IAV-specific antibody were 95.4 and 95.0
      %, respectively. Serological surveillance from 2009 to 2014 showed that ~7.58 %
      of feral swine in the USA were positive for IAV. Our findings confirm the
      susceptibility of IAV infection and the high transmission ability of IAV amongst
      feral swine, and also suggest the need for continued surveillance of IAVs in
      feral swine populations. 

PMID- 26297151
TI  - Detection of enzyme activities and their relation to serotypes of bovine and
      human group B streptococci.
AB  - Enzymatic properties of group B streptococci (GBS) serotypes from bovine milk and
      human routine vaginal specimens were investigated. Out of the 56 human and 66
      bovine GBS, 35 and 30 could be classified serologically by a co-agglutination
      test with type-specific antisera, respectively. Hyaluronidase (HYAL),
      streptokinase (SK) and protease activities were detected using culture media.
      HYAL activity was observed mostly in typable human GBS, and serotypes Ia, Ic and
      II comprised 77.3% of the typable strains producing HYAL. Bovine GBS serotypes
      II, III and VII comprised 87.5% of typable bovine strains exhibiting HYAL
      activity. SK activity was detected only in three human GBS. Human GBS serotypes
      Ia, Ic, II, III, VII and almost all typable bovine GBS strains showed protease
      activity. beta-D-glucosidase activity was frequently observed in human GBS,
      whereas N-acetyl-beta-D-glucosaminidase activity was mostly detected in non
      typable GBS from humans. These results indicate that different GBS serotypes
      could vary in their virulence properties, and bovine and human GBS isolates could
      not be differentiated by their enzyme activities. Use of the culture media
      appeared to be a simple-to-apply and useful method for the detection of
      extracellular enzyme activity such as HYAL, protease and SK.

PMID- 26297150
TI  - A robust blood gene expression-based prognostic model for castration-resistant
      prostate cancer.
AB  - BACKGROUND: Castration-resistant prostate cancer (CRPC) is associated with wide
      variations in survival. Recent studies of whole blood mRNA expression-based
      biomarkers strongly predicted survival but the genes used in these biomarker
      models were non-overlapping and their relationship was unknown. We developed a
      biomarker model for CRPC that is robust, but also captures underlying biological
      processes that drive prostate cancer lethality. METHODS: Using three independent
      cohorts of CRPC patients, we developed an integrative genomic approach for
      understanding the biological processes underlying genes associated with cancer
      progression, constructed a novel four-gene model that captured these changes, and
      compared the performance of the new model with existing gene models and other
      clinical parameters. RESULTS: Our analysis revealed striking patterns of myeloid-
      and lymphoid-specific distribution of genes that were differentially expressed in
      whole blood mRNA profiles: up-regulated genes in patients with worse survival
      were overexpressed in myeloid cells, whereas down-regulated genes were noted in
      lymphocytes. A resulting novel four-gene model showed significant prognostic
      power independent of known clinical predictors in two independent datasets
      totaling 90 patients with CRPC, and was superior to the two existing gene models.
      CONCLUSIONS: Whole blood mRNA profiling provides clinically relevant information
      in patients with CRPC. Integrative genomic analysis revealed patterns of
      differential mRNA expression with changes in gene expression in immune cell
      components which robustly predicted the survival of CRPC patients. The next step
      would be validation in a cohort of suitable size to quantify the prognostic
      improvement by the gene score upon the standard set of clinical parameters.

PMID- 26297152
TI  - Candida baotianmanensis sp. nov. and Candida pseudoviswanathii sp. nov., two
      ascosporic yeast species isolated from the gut of beetles.
AB  - Four yeast strains were isolated from the gut of beetles collected on Baotianman
      Mountain and People's Park of Nanyang in Henan Province, China. These strains
      produced unconjugated asci with one or two ellipsoidal to elongate ascospores in
      a persistent ascus. Phylogenetic analysis of the D1/D2 domains of the LSU rRNA
      gene sequences indicated that the isolates represent two novel sexual species in
      the Candida/Lodderomyces clade. Candida baotianmanensis sp. nov. was located in a
      statistically well-supported branch together with Candida maltosa. Candida
      pseudoviswanathii sp. nov. formed a subclade with its closest relative Candida
      viswanathii supported by a strong bootstrap value. The two novel species were
      distinguished from their most closely related described species, Candida maltosa
      and Candida viswanathii, in the D1/D2 LSU rRNA gene and internal transcribed
      spacer (ITS) sequences and in phenotypic traits. The type strain of Candida
      baotianmanensis sp. nov. is NYNU 14719T ( = CBS 13915T = CICC 33052T), and the
      type strain of Candida pseudoviswanathii sp. nov. is NYNU 14772T ( = CBS 13916T =
      CICC 33053T). The MycoBank numbers for Candida baotianmanensis sp. nov. and
      Candida pseudoviswanathii sp. nov. are MB 812621 and MB 812622. 

PMID- 26297154
TI  - Biosignatures for Astrobiology.

PMID- 26297153
TI  - Differences in extracellular matrix remodeling in the placenta of mares that
      retain fetal membranes and mares that deliver fetal membranes physiologically.
AB  - INTRODUCTION: In mammals, placenta separation at term may involve degradation of
      the extracellular matrix by matrix metalloproteinases (MMPs). The activity of
      MMPs is modulated by TIMPs. We hypothesized that the placentas of mares that
      deliver fetal membranes physiologically and those that retain fetal membranes
      (FMR) differ in terms of histology; mRNA expression of MMP-2 and MMP-9; protein
      expression of MMP-2, MMP-9, and TIMP-2; and the potential activity of both MMPs.
      METHODS: Placenta biopsies were taken from mares (n = 9; 4 FMR, 5 controls)
      immediately after foal expulsion. Retention was defined as failure to expel all
      fetal membranes within 3 h of expulsion. All mares were monitored for time of
      expulsion. The degree of allantochorial/endometrial adhesion was determined in
      FMR mares, and biopsies from all mares were histologically examined. mRNA
      expression, protein immunolocalization, protein amount and potential enzyme
      activity were determined with RT-PCR, immunohistochemistry, Western Blotting and
      zymography, respectively. RESULTS: FMR mares had strong to extremely strong
      allantochorial/endometrial adhesion, and significantly more connective tissue in
      the allantochorial villi than controls. The range of MMP-2 mRNA expression levels
      was more than 13 times greater in FMR mares than in controls. Protein content of
      both MMPs and TIMP-2 differed significantly between groups. The range of
      potential MMP-2 and MMP-9 activity was larger in FMR mares, and MMP-2 potential
      activity was 1.4 times higher in controls (P = 0.02). DISCUSSION: These results
      indicate differences in extracellular matrix remodeling in FMR mares and
      controls, and suggest dysregulation of MMP expression and activation in FMR
      mares.

PMID- 26297155
TI  - Atherosclerosis as a predictor of delayed recovery from lower urinary tract
      dysfunction after robot-assisted laparoscopic radical prostatectomy.
AB  - AIMS: The aim of the present study was to investigate whether atherosclerosis
      could be associated with lower urinary tract dysfunction in the early
      postoperative period after robot-assisted laparoscopic radical prostatectomy
      (RARP). METHODS: Eighty consecutive patients undergoing RARP were investigated.
      The severity of atherosclerosis was evaluated by the cardio-ankle vascular index
      (CAVI) before RARP. Patients were divided into two groups, the atherosclerotic
      group (CAVI >=9.0) and the control group (CAVI <9.0). International Prostate
      Symptom Score (IPSS), quality of life (QOL) index, uroflowmetry, post-void
      residual urine volume (PVR), frequency-volume charts, and the 1-hr pad test were
      compared between the two groups. Assessments were performed before RARP, and then
      at 1, 3, and 6 months after RARP. RESULTS: Preoperative subjective and objective
      parameters were not significantly different between the two groups. The voiding
      symptom score of the IPSS and the QOL index was significantly higher in the
      atherosclerotic group at 3 months after RARP (P = 0.035, P = 0.001,
      respectively). The maximum flow rate was consistently lower in the
      atherosclerotic group, reaching a significant difference at 6 months after RARP
      (P = 0.027). IPSS total and storage symptom scores, PVR, frequency, and urine
      loss were not significantly different between the groups after RARP. CONCLUSIONS:
      Atherosclerosis delayed the improvement of both voiding symptoms and voiding
      function after RARP, leading to aggravation of QOL in the early postoperative
      period. Atherosclerosis may be a predictor of slower recovery from transient
      lower urinary tract dysfunction immediately after RARP. Neurourol. Urodynam.
      35:920-925, 2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 26297156
TI  - [Administering GnRH Agonists in the luteal phase of Artificial Cycle Frozen
      Thawed Embryo Transfers. A prospective randomized study].
AB  - OBJECTIVE: Adding GnRH agonists in the luteal phase has recently been said to
      improve implantation in IVF treatment (increased rates of pregnancy and birth).
      Adding GnRH agonists could also be beneficial for frozen-thawed embryo transfers.
      The objective was to compare the administration of Gonadotropin Releasing Hormone
      (GnRH) agonists during implantation with usual progesterone supplementation in
      the artificial cycle of frozen-thawed embryo transfers. METHODS: A prospective
      randomized controlled trial was conducted in a reproductive medicine center in a
      university hospital including all women starting an artificial cycle of Frozen
      Thawed Embryo Transfers (FET). Two hundred and twenty women were randomized from
      September 2013 to June 2014. In the addition of GnRh agonists' group, two
      triptorelin injections of 0.1mg were carried out on the 4th day and on the 6th
      day following the introduction of progesterone. The primary outcome was the
      ongoing pregnancy rate. RESULTS: The ongoing pregnancy rate was higher (17 %
      versus 10.6 % P=0.29) when triptorelin was added, although the difference wasn't
      significant for the population as a whole. The increase proved to be significant
      in the case of day 2 embryos (34.6 % versus 10.3 % P<0.05) and of vitrified
      blastocysts (33.3% versus 12.5% P<0.05). CONCLUSION: The ongoing pregnancy rate
      for day 2 embryos and vitrified blastocysts significantly increased when GnRH
      agonists were added during implantation.

PMID- 26297157
TI  - [How I do... the antenatal diagnosis of a vasa previa with ultrasound].

PMID- 26297158
TI  - [Squamous cell carcinoma of the vulva and pregnancy: Tough choices].

PMID- 26297159
TI  - [A new stage towards the end of axillary lymph node dissection in breast cancer].

PMID- 26297160
TI  - [Laparoscopy in ART?].
AB  - The use of laparoscopy in infertility is currently controversial. However,
      laparoscopic treatment of tubal and peritoneal disease, or endometriosis improves
      natural fecundity and ART results. The use of laparoscopy in unexplained
      infertility can be considered because of underestimated pelvic pathology. The
      result of laparoscopy may help the practitioner for choosing spontaneous
      pregnancy or ART postoperative management. Although there is a lack of randomized
      study, laparoscopy is useful for a high overall pregnancy rate (surgery and ART
      treatment). Rather than opposing ART and laparoscopy, the integrated approach
      seems better for personal management. 

PMID- 26297161
TI  - [Axillary lymph node dissection after breast reconstruction by pedicled
      Latissimus dorsi: Operative steps and outcomes].
AB  - OBJECTIVES: We retrospectively reviewed all the cases of axillary lymph node
      dissection (ALND) performed within a year after an immediate breast
      reconstruction procedure by a pedicled Latissimus dorsi, which is transferred to
      the anterior thoracic wall through an axillary funnel. Operative technical steps
      are described taking account of the new anatomical relationship of the axilla.
      METHODS: We assessed postoperative immediate complications and late sequelaes.
      RESULTS: From 1999 to 2013, 21 ALND were performed. Immediate postoperative
      period was free of complication in 85% of cases when following the operative
      steps described in this work. Partial or total necrosis of the reconstructed
      breast did not occur. With a median follow-up of 64 months, 6 patients (28% of
      the whole population) presented at least one sequelae like a feeling of heavy arm
      (n=2, 9%) or a lymphedema (n=3, 14%), a chronic neuropathic pain (n=4, 19%) or a
      limitation in the arm range of motion (n=2, 9%). CONCLUSION: ALND after immediate
      breast reconstruction by a pedicled Latissimus dorsi is feasible and safe,
      without any additional postoperative complication in comparison with a classic
      ALND.

PMID- 26297162
TI  - [Legalization of social egg freezing would make oocyte donation management
      easier].

PMID- 26297163
TI  - [Infertility over forty: Pros and cons of IVF].
AB  - The population attempting pregnancy and having babies is ageing. The declining
      fertility potential and the late age of motherhood are increasing significantly
      the number of patients over forty consulting infertility specialists. Assisted
      reproductive technologies (ART) cannot compensate the natural decline in
      fertility with age. In France, in public hospital, ART is free of charge for
      women until 43 years, over 43, social insurance does not reimburse ART. Hence, 43
      years is the usual limit, but between 40 and 42 is ART useful? The answer varies
      according to physicians, couples or society. On medical level, the etiology of
      the infertility must be taken into account. If there is an explanation to
      infertility (male or tubal infertility) ART is better than abstention. If the
      infertility is only due to age the question is raised. In France, the
      reimbursement by the society of a technique with very low results is discussed.
      However efficacy is not absolutely compulsory in Medicine. On the opposite to
      give false hopes may be discussed too. To obtain a reasonable consensus is rather
      difficult. 

PMID- 26297164
TI  - [On the pill over the counter: Is it now possible in France?].

PMID- 26297165
TI  - [Post-mortem perinatal imaging: State of the art and perspectives, with an
      emphasis on ultrasound].
AB  - The fields of application of post-mortem imaging have been exponentially growing
      for 10 years. Its potential to identify the cause of death in trauma and
      ballistic cases is now properly documented. In pediatric and perinatal practice,
      large significant series are less available, except for MRI and central nervous
      system analysis where scientific evidence is now robust. After a short historical
      and state-of-the-art review, we will try to depict the way we see the future of
      this sub-specialty of post-mortem imaging, especially in specific perinatal
      situations. 

PMID- 26297166
TI  - Further characterization of the role of the mitochondrial high-mobility group box
      protein in the intracellular redox environment of Aspergillus nidulans.
AB  - HmbB, a predominantly mitochondrial high-mobility group box (HMGB) protein, of
      Aspergillus nidulans affects diverse biological activities, such as
      sterigmatocystin production, the maintenance of mitochondrial DNA copy number,
      germination of asexual and sexual spores, and protection against oxidative stress
      agents. We hypothesized that the latter correlates with an unbalanced
      intracellular redox state, in which case, a not yet fully characterized
      physiological function could be attributed to this mitochondrial HMGB protein.
      Here, we studied the intracellular redox environment and oxidative stress
      tolerance in hmbB+ and hmbBDelta strains under normal and oxidative stress
      conditions by measuring glutathione redox couple, intracellular reactive oxygen
      species (ROS) content and ROS-protecting enzyme activities. Our results revealed
      that the intracellular redox environment is different in hmbBDelta conidia and
      mycelia from that of hmbB+, and shed light on the seemingly contradictory
      difference in the tolerance of hmbBDelta mycelia to diamide and menadione
      oxidative stressors.

PMID- 26297167
TI  - Biodegradable DNA-Brush Block Copolymer Spherical Nucleic Acids Enable
      Transfection Agent-Free Intracellular Gene Regulation.
AB  - By grafting multiple DNA strands onto one terminus of a polyester chain, a DNA
      brush block copolymer that can assemble into micelle structure is constructed.
      These micelle spherical nucleic acids have a density of nucleic acids that is
      substantively higher than linear DNA block copolymer structures, which makes them
      effective cellular transfection and intracellular gene regulation agents. 

PMID- 26297168
TI  - An investigation of vancomycin minimum inhibitory concentration creep among
      methicillin-resistant Staphylococcus aureus strains isolated from pediatric
      patients and healthy children in Northern Taiwan.
AB  - BACKGROUND AND PURPOSE: The phenomenon of vancomycin minimum inhibitory
      concentration (MIC) creep is an increasingly serious problem in the treatment of
      methicillin-resistant Staphylococcus aureus (MRSA) infections. In this study, we
      investigated the vancomycin and daptomycin MIC values of MRSA strains isolated
      from pediatric patients and MRSA colonized healthy children. Then, we assessed
      whether there was evidence of clonal dissemination for strains with an MIC to
      vancomycin of >= 1.5 MUg/mL. METHODS: We collected clinical MRSA isolates from
      pediatric patients and from healthy children colonized with MRSA during 2008-2012
      at a tertiary medical center in northern Taiwan and obtained vancomycin and
      daptomycin MIC values using the Etest method. Pulse-field gel electrophoresis
      (PFGE) and staphylococcal cassette chromosome (SCCmec) typing were used to assess
      clonal dissemination for strains with an MIC to vancomycin of >= 1.5 MUg/mL.
      RESULTS: A total 195 MRSA strains were included in this study; 87 were isolated
      patients with a clinical MRSA infection, and the other 108 strains from nasally
      colonized healthy children. Vancomycin MIC>=1.5 MUg/mL was seen in more clinical
      isolates (60/87, 69%) than colonized isolates (32/108, 29.6%), p < 0.001. The
      PFGE typing of both strains revealed multiple pulsotypes. CONCLUSION: Vancomycin
      MIC creeps existed in both clinical MRSA isolates and colonized MRSA strains.
      Great diversity of PFGE typing was in both strains collected. There was no
      association between the clinical and colonized MRSA isolates with vancomycin MIC
      creep.

PMID- 26297170
TI  - Direct evidence of bacterial biofilms in otitis media. 2001.

PMID- 26297172
TI  - Kribbella mirabilis sp. nov., isolated from rhizosphere soil of a herbaceous
      plant, Mirabilis jalapa L.
AB  - Strain XMU 706(T), isolated from the rhizosphere soil of a herbaceous plant,
      Mirabilis jalapa L., collected from Xiamen City, China, was characterized using a
      polyphasic approach to clarify its taxonomic position. Strain XMU 706(T) shared
      the highest 16S rRNA gene sequence similarity with Kribbella antibiotica YIM
      31530(T) (97.2%), and formed a distinct branch in the subclade of the genus
      Kribbella in the 16S rRNA gene phylogenetic tree. The genetic distances of gyrase
      subunit B gene (gyrB) sequence between strain XMU 706(T) and other species of the
      genus Kribbella ranged from 0.045 to 0.116, greater than the threshold value of
      0.014 for species delineation of this genus. DNA-DNA hybridization experiments
      gave a DNA-DNA relatedness value of 34.82 +/- 6.31% between strain XMU 706(T) and
      K. antibiotica YIM 31530(T). The chemotaxonomic properties further supported the
      assignment of strain XMU 706(T) to the genus Kribbella. ll-Diaminopimelic acid
      was the diagnostic amino acid in the cell-wall peptidoglycan and cell
      hydrolysates contained ribose and glucose. The major menaquinone was MK-9(H4).
      The polar lipids comprised diphosphatidylglycerol, phosphatidylglycerol,
      phosphatidylcholine and other unidentified phospholipids and lipids. The major
      fatty acids of the strain were anteiso-C15 : 0 and iso-C15 : 0, and the G+C
      content of the genomic DNA was 67.3 mol%. Based on the results of phylogenetic
      analysis, phenotypic and genotypic characterization, strain XMU 706(T) represents
      a novel species of the genus Kribbella, for which the name Kribbella mirabilis
      sp. nov. is proposed. The type strain is XMU 706(T) ( = KCTC 29676(T) = MCCC
      1K00429(T)).

PMID- 26297173
TI  - A Systematic Review of Iran's Medicinal Plants With Anticancer Effects.
AB  - Increase in cases of various cancers has encouraged the researchers to discover
      novel, more effective drugs from plant sources. This study is a review of
      medicinal plants in Iran with already investigated anticancer effects on various
      cell lines. Thirty-six medicinal plants alongside their products with anticancer
      effects as well as the most important plant compounds responsible for the plants'
      anticancer effect were introduced. Phenolic and alkaloid compounds were
      demonstrated to have anticancer effects on various cancers in most studies. The
      plants and their active compounds exerted anticancer effects by removing free
      radicals and antioxidant effects, cell cycle arrest, induction of apoptosis, and
      inhibition of angiogenesis. The investigated plants in Iran contain the compounds
      that are able to contribute effectively to fighting cancer cells. Therefore, the
      extract and active compounds of the medicinal plants introduced in this review
      article could open a way to conduct clinical trials on cancer and greatly help
      researchers and pharmacists develop new anticancer drugs. 

PMID- 26297174
TI  - Prospective Evaluation of Few Homeopathic Rubrics of Kent's Repertory From
      Bayesian Perspective.
AB  - Absolute grading system of homeopathic repertories poses substantial threat to
      reliability; however, it may be resolved by evaluating rubrics prospectively
      using likelihood ratio (LR). The authors evaluated few "physical general" rubrics
      from Kent's repertory-"chilly," "hot," "ambithermal," "preference for hot/cold
      food," "desire/aversion for fish/egg/meat/sour/pungent/salt/sweet/bitter"
      prospectively in West Bengal, India, for 1.5 years using the Outcome Related to
      Impact on Daily Living scale. Per symptom/rubric, LRs < 1.5 were discarded. A
      total of 2039 encounters were analyzed for thermal relations and 4715 for
      desires/aversions for specific food items. Comparison with Kent's repertory
      revealed discrepancies. One new rubric with corresponding medicines was suggested
      to be introduced, new entries of medicines were recommended, and some seemed to
      maintain their ascribed importance. The authors refrained from converting LRs
      into typefaces prematurely; still they propose introducing LR to repertories for
      a structural update, changing its use, and enabling homeopaths to make more
      reliable predictions. 

PMID- 26297175
TI  - Determinants of Proteolysis and Cell-Binding for the Shigella flexneri Cytotoxin,
      SigA.
AB  - Shigella flexneri secretes an enterotoxic, SPATE family autotransporter (AT),
      SigA, which has cytopathic activity towards cultured epithelial cells. Its
      cytopathic activity is due to its ability to degrade the cytoskeletal protein,
      alpha-fodrin. The mechanisms by which AT toxins target cells and tissues differ
      and the details of how SigA acts are not known. In the current study, the
      determinants of proteolysis and cell-targeting for SigA were determined. We
      demonstrate that the SigA passenger or alpha-domain consists of two functionally
      distinct domains, designated alpha1 and alpha2, which are sufficient to specify
      proteolytic and cell-binding activities, respectively.

PMID- 26297177
TI  - IL-20 in rheumatoid arthritis.
AB  - Rheumatoid arthritis, a systemic autoimmune disease, causes chronic joint
      inflammation and bone destruction. Interleukin (IL)-20's association with this
      disease, and its expression and regulation has been extensively studied since
      2006. Anti-IL-20 antibody has paved the way to clinical trials aimed at blocking
      the pathogenic actions of IL-20 in rheumatoid arthritis. This review focuses on
      current knowledge of IL-20's involvement in the pathogenesis of rheumatoid
      arthritis.

PMID- 26297176
TI  - Combination of GM-CSF With Fludarabine-Containing Regimens in Chronic Lymphocytic
      Leukemia and Indolent Non-Hodgkin Lymphoma.
AB  - BACKGROUND: Granulocyte-monocyte colony stimulating factor (GM-CSF) is a
      hematopoietic cytokine with immunomodulatory activity that has preclinical
      evidence for enhancement of antitumor immunity when administered in combination
      with chemotherapy. We evaluated the utility of GM-CSF with chemoimmunotherapy in
      patients with indolent non-Hodgkin lymphoma (NHL) and chronic lymphocytic
      leukemia (CLL) in a pilot study. PATIENTS AND METHODS: Patients with previously
      untreated, relapsed, or refractory indolent NHL or CLL were treated with GM-CSF,
      rituximab, fludarabine, and cyclophosphamide or mitoxantrone for a maximum of 6
      cycles. RESULTS: Sixteen patients were enrolled, including 1 patient who did not
      receive study therapy. Of the 15 remaining patients, 6 received cyclophosphamide
      and 9 received mitoxantrone in combination with fludarabine, rituximab, and GM
      CSF. The overall response rate for all patients was 87%. Nine patients have
      subsequently had relapse of their disease, and 6 remained in remission at last
      study contact. There were no toxic deaths during the study. CONCLUSION: GM-CSF
      based chemoimmunotherapy was well-tolerated and resulted in a high response rate
      and warrants evaluation in larger studies.

PMID- 26297178
TI  - Acute Myocardial Infarction in a Neonate Caused by a Coronary Thrombosis: a
      Considerable Diagnostic and Therapeutic Challenge.

PMID- 26297180
TI  - Evaluation of microbial diversity in the pilot-scale beer brewing process by
      culture-dependent and culture-independent method.

PMID- 26297179
TI  - Multimarker Strategy for Heart Failure Prognostication. Value of Neurohormonal
      Biomarkers: Neprilysin vs NT-proBNP.
AB  - INTRODUCTION AND OBJECTIVES: Neprilysin breaks down numerous vasoactive peptides.
      The soluble form of neprilysin, which was recently identified in heart failure,
      is associated with cardiovascular outcomes. Within a multibiomarker strategy, we
      directly compared soluble neprilysin and N-terminal pro-B-type natriuretic
      peptide as risk stratifiers in a real-life cohort of heart failure patients.
      METHODS: Soluble neprilysin, N-terminal pro-B-type natriuretic peptide, ST2, and
      high-sensitivity troponin T levels were measured in 797 consecutive ambulatory
      heart failure patients followed up for 4.7 years. Comprehensive multivariable
      analyses and soluble neprilysin vs N-terminal pro-B-type natriuretic peptide head
      to-head assessments of performance were performed. A primary composite endpoint
      included cardiovascular death or heart failure hospitalization. A secondary
      endpoint explored cardiovascular death alone. RESULTS: Median soluble neprilysin
      and N-terminal pro-B-type natriuretic peptide concentrations were 0.64ng/mL and
      1187 ng/L, respectively. Both biomarkers significantly correlated with age
      (P<.001) and ST2 (P<.001), but only N-terminal pro-B-type natriuretic peptide
      significantly correlated with estimated glomerular filtration rate (P<.001), body
      mass index (P<.001), left ventricular ejection fraction (P=.02) and high
      sensitivity troponin T (P<.001). In multivariable Cox regression analyses,
      soluble neprilysin remained independently associated with the composite endpoint
      (hazard ratio=1.14; 95% confidence interval, 1.02-1.27; P=.03) and cardiovascular
      death (hazard ratio=1.15; 95% confidence interval, 1.01-1.31; P=.04), but N
      terminal pro-B-type natriuretic peptide did not. The head-to-head soluble
      neprilysin vs N-terminal pro-B-type natriuretic peptide comparison showed good
      calibration and similar discrimination and reclassification for both
      neurohormonal biomarkers, but only soluble neprilysin improved overall goodness
      of-fit. CONCLUSIONS: When added to a multimarker strategy, soluble neprilysin
      remained an independent prognosticator, while N-terminal pro-B-type natriuretic
      peptide lost significance as a risk stratifier in ambulatory patients with heart
      failure. Both biomarkers performed similarly in head-to-head analyses.

PMID- 26297181
TI  - Reconsideration of the derivation of Most Probable Numbers, their standard
      deviations, confidence bounds and rarity values.

PMID- 26297182
TI  - Prevalence of functional gastrointestinal disorders in school-aged children in El
      Salvador.
AB  - BACKGROUND: We studied the epidemiology of functional gastrointestinal disorders
      (FGIDs) in school-aged Salvadoran children using standardized diagnostic
      criteria. AIMS: To determine the prevalence of FGIDs in school-aged children in
      El Salvador. MATERIAL AND METHODS: A total of 395 children participated in the
      study (one public school and one private school). School children completed the
      Spanish version of the Questionnaire on Pediatric Gastrointestinal Symptoms-Rome
      III (QPGS-III), an age-appropriate and previously validated instrument for
      diagnosing FGIDs according to the Rome III criteria. Sociodemographic (age, sex,
      type of school) and familial (family structure and size, family history of
      gastrointestinal disorders) data were obtained. RESULTS: The mean age of the
      sample was 11.8 years +/- 1.6 SD (median 10, range 8-15) and 59% of the
      participants were female. Eighty-one children met the diagnostic criteria for a
      FGID (20%). Defecation disorders were the most common group of FGIDs. Functional
      constipation was diagnosed in 10% of the children and 9.25% were diagnosed with
      abdominal pain-related FGIDs (most commonly IBS, 3.75%). IBS overlapped with
      functional dyspepsia in 11% of the cases. Children with FGIDs frequently reported
      nausea. Children attending private school and older children had significantly
      more FGIDs than children in public school and younger children. CONCLUSIONS:
      FGIDs are common in school-aged Salvadoran children.

PMID- 26297184
TI  - Biomimetic Hydroxyapatite Growth on Functionalized Surfaces of Ti-6Al-4V and Ti
      Zr-Nb Alloys.
AB  - A biomimetic approach for coating titanium-containing alloys with hydroxyapatite
      (HA) is reported in the article. Two types of Ti-containing alloys were chosen as
      an object for coating: Ti-6Al-4V (recommended for orthopedic application) and a
      novel highly biocompatible Ti-Zr-Nb alloy, with good mechanical compatibility due
      to a modulus that is more close to that of human bones (E ~ 50 GPa instead of 110
      GPa in Ti-6Al-4V). Coating process was carried out in a 10*-concentrated
      simulated body fluid (SBF)-synthetic analog of human body plasma. The effect of
      oxidized and carboxylated alloy surface on formation of biomimetic hydroxyapatite
      has been studied. By XRD, we found influence of thermal conditions on HA crystal
      formation and size. SEM images and Fourier transform infrared confirmed that
      hydroxyapatite with different morphology, crystallinity, and Ca/P ratio formed on
      metallic surfaces. X-ray photoelectron spectroscopy showed that in the Ti-6AL-4V
      sample the observed Ca/P ratio reach 0.97, whereas in the Ti-Zr-Nb sample the
      observed Ca/P ratio reach 1.15. 

PMID- 26297183
TI  - Residual gammaH2AX foci after ex vivo irradiation of patient samples with known
      tumour-type specific differences in radio-responsiveness.
AB  - PURPOSE: To apply our previously published residual ex vivo gammaH2AX foci method
      to patient-derived tumour specimens covering a spectrum of tumour-types with
      known differences in radiation response. In addition, the data were used to
      simulate different experimental scenarios to simplify the method. MATERIALS AND
      METHODS: Evaluation of residual gammaH2AX foci in well-oxygenated tumour areas of
      ex vivo irradiated patient-derived tumour specimens with graded single doses was
      performed. Immediately after surgical resection, the samples were cultivated for
      24h in culture medium prior to irradiation and fixed 24h post-irradiation for
      gammaH2AX foci evaluation. Specimens from a total of 25 patients (including 7
      previously published) with 10 different tumour types were included. RESULTS:
      Linear dose response of residual gammaH2AX foci was observed in all specimens
      with highly variable slopes among different tumour types ranging from 0.69 (95%
      CI: 1.14-0.24) to 3.26 (95% CI: 4.13-2.62) for chondrosarcomas (radioresistant)
      and classical seminomas (radiosensitive) respectively. Simulations suggest that
      omitting dose levels might simplify the assay without compromising robustness.
      CONCLUSION: Here we confirm clinical feasibility of the assay. The slopes of the
      residual foci number are well in line with the expected differences in radio
      responsiveness of different tumour types implying that intrinsic radiation
      sensitivity contributes to tumour radiation response. Thus, this assay has a
      promising potential for individualized radiation therapy and prospective
      validation is warranted.

PMID- 26297185
TI  - Homogeneous matrix deposition on dried agar for MALDI imaging mass spectrometry
      of microbial cultures.
AB  - Matrix deposition on agar-based microbial colonies for MALDI imaging mass
      spectrometry is often complicated by the complex media on which microbes are
      grown. This Application Note demonstrates how consecutive short spray pulses of a
      matrix solution can form an evenly closed matrix layer on dried agar. Compared
      with sieving dry matrix onto wet agar, this method supports analyte
      cocrystallization, which results in significantly more signals, higher signal-to
      noise ratios, and improved ionization efficiency. The even matrix layer improves
      spot-to-spot precision of measured m/z values when using TOF mass spectrometers.
      With this technique, we established reproducible imaging mass spectrometry of
      myxobacterial cultures on nutrient-rich cultivation media, which was not possible
      with the sieving technique. Graphical Abstract ?. 

PMID- 26297186
TI  - Characterization and Modeling of the Collision Induced Dissociation Patterns of
      Deprotonated Glycosphingolipids: Cleavage of the Glycosidic Bond.
AB  - Glycosphingolipid fragmentation behavior was investigated by combining results
      from analysis of a series of negative ion tandem mass spectra and molecular
      modeling. Fragmentation patterns extracted from 75 tandem mass spectra of mainly
      acidic glycosphingolipid species (gangliosides) suggest prominent cleavage of the
      glycosidic bonds with retention of the glycosidic oxygen atom by the species
      formed from the reducing end (B and Y ion formation). Dominant product ions arise
      from dissociation of sialic acids glycosidic bonds whereas product ions resulting
      from cleavage of other glycosidic bonds are less abundant. Potential energy
      surfaces and unimolecular reaction rates of several low-energy fragmentation
      pathways leading to cleavage of glycosidic bonds were estimated in order to
      explain observed dissociation patterns. Glycosidic bond cleavage in both neutral
      (unsubstituted glycosyl group) and acidic glycosphingolipids was the outcome of
      the charge-directed intramolecular nucleophilic substitution (SN2) mechanism.
      According to the suggested mechanism, the nucleophile in a form of carboxylate or
      oxyanion attacks the carbon at position one of the sugar ring, simultaneously
      breaking the glycosidic bond and yielding an epoxide. For gangliosides,
      unimolecular reaction rates suggest that dominant product ions related to the
      cleavage of sialic acid glycosidic bonds are formed via direct dissociation
      channels. On the other hand, low abundant product ions related to the
      dissociation of other glycosidic bonds are more likely to be the result of
      sequential dissociation. Although results from this study mainly contribute to
      the understanding of glycosphingolipid fragmentation chemistry, some mechanistic
      findings regarding cleavage of the glycosidic bond may be applicable to other
      glycoconjugates.

PMID- 26297187
TI  - A model comparing how rapidly transfusion of solvent detergent plasma restores
      clotting factors versus infusion of albumin-saline.
AB  - BACKGROUND: A recent randomized controlled trial demonstrated the bioequivalence
      between universally applicable and AB0 compatible transfusion plasma in healthy
      volunteers. There was a limited change in coagulation factor levels and
      inhibitors before and after plasmapheresis and subsequent plasma transfusion. The
      aim of this extension trial was to investigate the true capacity of these plasma
      products to restore baseline levels of coagulation factors and inhibitors after
      plasma depletion in comparison to haemodilution induced by infusion of albumin
      solution. MATERIALS AND METHODS: Fourteen healthy subjects, who completed both
      plasma transfusion periods, underwent an additional plasmapheresis (600 mL)
      followed by an infusion of 1200 mL albumin (3.125%) in a third period. RESULTS:
      The fibrinogen levels, as well as other clotting factors (FII, FV, FVII and FXI),
      decreased by 10% after plasmapheresis, and subsequent infusion of albumin
      solution further aggravated this drop in clotting factors to approximately 20
      25%. The clotting factors with a long half-life were not even restored 24 hours
      after infusion of albumin solution, whereas those with a short half-life were
      replenished by endogenous synthesis within 24 hours. In contrast, transfusion of
      either plasma product rapidly restored all clotting parameters and inhibitors
      (protein S and plasmin inhibitor) immediately after transfusion. CONCLUSION: This
      study demonstrates that albumin solution induces an enhanced dilution of clotting
      factors and inhibitors, whereas both plasma products quickly compensated for the
      experimental loss of these plasma proteins.

PMID- 26297188
TI  - Factors associated with positive attitude towards blood donation among medical
      students.
AB  - The aim of this study was to assess attitudes and practice of blood donation
      among medical students. Medical students were recruited at Medical Faculty,
      University of Belgrade, Serbia. Of 973 students, 38.4% of freshmen and 41.4% of
      final year students have donated blood (chi(2) = 0.918, p = 0.186). Blood donors
      had significantly more positive attitude towards some aspects of blood donation.
      Being female, residing in a city other than the capital and previous blood
      donation experience were independent predictors of positive attitude towards
      being a blood donor to an unknown person. Efforts are required to augment blood
      donor pool among future physicians.

PMID- 26297189
TI  - Frequent anemic blood donors: What should we do?

PMID- 26297190
TI  - A quantitative model to predict blood use in adult orthotopic liver
      transplantation.
AB  - To identify preoperative predictors for the use of any blood component during and
      after orthotopic liver transplantation (OLT), we performed a retrospective
      analysis on 602 OLT patients who were randomly split into a training set (n =
      482) and a validation set (n = 120). Hemoglobin and calculated MELD score were
      identified as independent predictors for blood use using bootstrap aggregation. A
      logistic regression model constructed using both variables showed comparable
      performance in the training and validation sets. Predictive scores can be
      obtained from a nomogram, and a score above -2.328 predicted transfusion of any
      blood component with a positive predictive value of 97% and 96% in the training
      and validation sets, respectively.

PMID- 26297191
TI  - How I became a biochemist: For Bill Whelan's Festschrift.

PMID- 26297192
TI  - Estimation of reference curves for the urinary steroid metabolome in the first
      year of life in healthy children: Tracing the complexity of human postnatal
      steroidogenesis.
AB  - CONTEXT: Complex steroid disorders such as P450 oxidoreductase deficiency or
      apparent cortisone reductase deficiency may be recognized by steroid profiling
      using chromatographic mass spectrometric methods. These methods are highly
      specific and sensitive, and provide a complete spectrum of steroid metabolites in
      a single measurement of one sample which makes them superior to immunoassays. The
      steroid metabolome during the fetal-neonatal transition is characterized by (a)
      the metabolites of the fetal-placental unit at birth, (b) the fetal adrenal
      androgens until its involution 3-6 months postnatally, and (c) the steroid
      metabolites produced by the developing endocrine organs. All these developmental
      events change the steroid metabolome in an age- and sex-dependent manner during
      the first year of life. OBJECTIVE: The aim of this study was to provide normative
      values for the urinary steroid metabolome of healthy newborns at short time
      intervals in the first year of life. METHODS: We conducted a prospective,
      longitudinal study to measure 67 urinary steroid metabolites in 21 male and 22
      female term healthy newborn infants at 13 time-points from week 1 to week 49 of
      life. Urine samples were collected from newborn infants before discharge from
      hospital and from healthy infants at home. Steroid metabolites were measured by
      gas chromatography-mass spectrometry (GC-MS) and steroid concentrations corrected
      for urinary creatinine excretion were calculated. RESULTS: 61 steroids showed age
      and 15 steroids sex specificity. Highest urinary steroid concentrations were
      found in both sexes for progesterone derivatives, in particular 20alpha-DH-5alpha
      DH-progesterone, and for highly polar 6alpha-hydroxylated glucocorticoids. The
      steroids peaked at week 3 and decreased by ~80% at week 25 in both sexes. The
      decline of progestins, androgens and estrogens was more pronounced than of
      glucocorticoids whereas the excretion of corticosterone and its metabolites and
      of mineralocorticoids remained constant during the first year of life.
      CONCLUSION: The urinary steroid profile changes dramatically during the first
      year of life and correlates with the physiologic developmental changes during the
      fetal-neonatal transition. Thus detailed normative data during this time period
      permit the use of steroid profiling as a powerful diagnostic tool.

PMID- 26297193
TI  - Super paramagnetic nanoparticles for the diagnostic imaging of pancreatic cancer.

PMID- 26297194
TI  - 7p22.1 microduplication syndrome: Clinical and molecular characterization of an
      adult case and review of the literature.
AB  - A new 7p22.1 microduplication syndrome characterized by intellectual disability,
      speech delay and craniofacial dysmorphisms, such as macrocephaly, hypertelorism
      and ear anomalies, has been outlined by the description of two patients with
      interstitial microduplications confined to 7p22.1 and the recently defined
      minimal overlapping 430 kb critical region including five genes. Here we report
      on the first adult patient aged 35 years with moderate intellectual disability,
      psychomotor delay, facial dysmorphisms, cryptorchidism and cardiac anomalies, who
      carries two close microduplications at 7p22.1 of about 900 and 150 kb,
      respectively. The proximal smaller duplication includes three coding genes and
      maps outside the minimal described overlapping duplicated region, while the
      larger one represents the smallest 7p22.1 microduplication reported so far, as it
      encompasses the entire minimal region with only four additional genes. We compare
      the phenotype of our patient with that of the few reported cases and discuss on
      candidate genes in order to enhance the knowledge on genotype-phenotype
      correlation in 7p22.1 duplication syndrome. 

PMID- 26297195
TI  - Integrated multi-omics analysis supports role of lysophosphatidylcholine and
      related glycerophospholipids in the Lotus japonicus-Glomus intraradices
      mycorrhizal symbiosis.
AB  - Interaction of plant roots with arbuscular mycorrhizal fungi (AMF) is a complex
      trait resulting in cooperative interactions among the two symbionts including
      bidirectional exchange of resources. To study arbuscular mycorrhizal symbiosis
      (AMS) trait variation in the model plant Lotus japonicus, we performed an
      integrated multi-omics analysis with a focus on plant and fungal phospholipid
      (PL) metabolism and biological significance of lysophosphatidylcholine (LPC). Our
      results support the role of LPC as a bioactive compound eliciting cellular and
      molecular response mechanisms in Lotus. Evidence is provided for large
      interspecific chemical diversity of LPC species among mycorrhizae with related
      AMF species. Lipid, gene expression and elemental profiling emphasize the Lotus
      Glomus intraradices interaction as distinct from other arbuscular mycorrhizal
      (AM) interactions. In G. intraradices, genes involved in fatty acid (FA)
      elongation and biosynthesis of unsaturated FAs were enhanced, while in Lotus, FA
      synthesis genes were up-regulated during AMS. Furthermore, FAS protein
      localization to mitochondria suggests FA biosynthesis and elongation may also
      occur in AMF. Our results suggest the existence of interspecific partitioning of
      PL resources for generation of LPC and novel candidate bioactive PLs in the Lotus
      G. intraradices symbiosis. Moreover, the data advocate research with
      phylogenetically diverse Glomeromycota species for a broader understanding of the
      molecular underpinnings of AMS. 

PMID- 26297196
TI  - Stress testing in patients with chronic kidney disease: The need for ancillary
      markers for effective risk stratification and prognosis.

PMID- 26297198
TI  - Learning patient-centred communication: The journey and the territory.
AB  - OBJECTIVE: The student entering medical school is about to undergo a
      socialisation process that profoundly shapes their development as a professional.
      A central feature is the formal and informal curriculum on the doctor-patient
      relationship and patient-centred communication. In this paper I will chart some
      of the features of the student journey which might impact on learning and
      practice. KEY FEATURES: The medical undergraduate's role is largely that of
      observer and learner, rather than a provider of care, so much of the formal
      teaching on patient-centred communication is within simulated practice. Clinical
      practice environments are the most powerful influences on learning about
      professional behaviour. Challenges for educational practitioners include how to
      support authenticity in learners, respond to their agendas, and foster insight to
      enable flexibility about communication in different contexts. Parallels between
      the doctor-patient relationship and the student-tutor relationship are explored
      for their relevance. A number of educational theories can inform curriculum
      design and educational practice, notably Vygotsky's Zone of Proximal Development.
      CONCLUSION: Application of this and other social learning theories, together with
      students' reflections can enrich our planning of educational interventions and
      understanding of their impact.

PMID- 26297199
TI  - alpha-Lactalbumin:Oleic Acid Complex Spontaneously Delivers Oleic Acid to
      Artificial and Erythrocyte Membranes.
AB  - Human alpha-lactalbumin made lethal to tumor cells (HAMLET) is a tumoricidal
      complex consisting of human alpha-lactalbumin and multiple oleic acids (OAs). OA
      has been shown to play a key role in the activity of HAMLET and its related
      complexes, generally known as protein-fatty acid (PFA) complexes. In contrast to
      what is known about the fate of the protein component of such complexes,
      information about what happens to OA during their action is still lacking. We
      monitored the membrane, OA and protein components of bovine alpha-lactalbumin
      complexed with OA (BLAOA; a HAMLET-like substance) and how they associate with
      each other. Using ultracentrifugation, we found that the OA and lipid components
      follow each other closely. We then firmly identify a transfer of OA from BLAOA to
      both artificial and erythrocyte membranes, indicating that natural cells respond
      similarly to BLAOA treatment as artificial membranes. Uncomplexed OA is unable to
      similarly affect membranes at the conditions tested, even at elevated
      concentrations. Thus, BLAOA can spontaneously transfer OA to a lipid membrane.
      After the interaction with the membrane, the protein is likely to have lost most
      or all of its OA. We suggest a mechanism for passive import of mainly uncomplexed
      protein into cells, using existing models for OA's effect on membranes. Our
      results are consistent with a membrane destabilization mediated predominantly by
      OA insertion being a significant contribution to PFA cytotoxicity. 

PMID- 26297200
TI  - Genotyping of 75 SNPs using arrays for individual identification in five
      population groups.
AB  - Single nucleotide polymorphism (SNP) typing offers promise to forensic genetics.
      Various strategies and panels for analyzing SNP markers for individual
      identification have been published. However, the best panels with fewer identity
      SNPs for all major population groups are still under discussion. This study aimed
      to find more autosomal SNPs with high heterozygosity for individual
      identification among Asian populations. Ninety-six autosomal SNPs of 502 DNA
      samples from unrelated individuals of five population groups (208 Taiwanese Han,
      83 Filipinos, 62 Thais, 69 Indonesians, and 80 individuals with European, Near
      Eastern, or South Asian ancestry) were analyzed using arrays in an initial
      screening, and 75 SNPs (group A, 46 newly selected SNPs; groups B, 29 SNPs based
      on a previous SNP panel) were selected for further statistical analyses. Some
      SNPs with high heterozygosity from Asian populations were identified. The
      combined random match probability of the best 40 and 45 SNPs was between 3.16 *
      10(-17) and 7.75 * 10(-17) and between 2.33 * 10(-19) and 7.00 * 10(-19),
      respectively, in all five populations. These loci offer comparable power to short
      tandem repeats (STRs) for routine forensic profiling. In this study, we
      demonstrated the population genetic characteristics and forensic parameters of 75
      SNPs with high heterozygosity from five population groups. This SNPs panel can
      provide valuable genotypic information and can be helpful in forensic casework
      for individual identification among these populations. 

PMID- 26297202
TI  - Understanding the socio-economic and sexual behavioural correlates of male
      circumcision across eleven voluntary medical male circumcision priority countries
      in southeastern Africa.
AB  - BACKGROUND: Male circumcision (MC) has been demonstrated to be effective and cost
      effective for HIV/AIDS prevention. Global guidance to adopt this intervention was
      announced in 2007 for countries with high HIV/AIDS prevalence and low MC
      prevalence. However, scale up of voluntary medical male circumcision (VMMC)
      programs in MC priority countries have been slow. Many of these countries have
      particular cultural barriers that impede uptake of this effective intervention.
      This analysis explored correlates of MC status among men and their socio
      economic, health and sexual behaviour factors using DHS data (2006-2011) from 11
      MC priority countries. METHODS: Our analysis included univariate unadjusted
      analyses for individual countries and the region (by combining all countries into
      one dataset) and a multiple logistic regression model. RESULTS: Individual
      country results vary widely but alignment was mostly found between unadjusted
      analyses and multiple logistic regression model. The model found that men who are
      of the Muslim faith, reside in urban areas, have higher or secondary education
      attainment, hold professional occupations, and be in the richest wealth quintile
      are more likely to be circumcised. Circumcision is also positively correlated
      with lower reports of STIs, safe sexual behaviour, and HIV/AIDS prevention
      knowledge. CONCLUSIONS: Since the data collected predate VMMC program launch in
      these countries, results can only indicate baseline associations. However,
      characteristics of these existing circumcision practices may be utilized for
      better population targeting and program management to achieve higher impact with
      this effective prevention strategy.

PMID- 26297201
TI  - CX3CR1 is an important surface molecule for respiratory syncytial virus infection
      in human airway epithelial cells.
AB  - Respiratory syncytial virus (RSV) is a major cause of severe pneumonia and
      bronchiolitis in infants and young children, and causes disease throughout life.
      Understanding the biology of infection, including virus binding to the cell
      surface, should help develop antiviral drugs or vaccines. The RSV F and G
      glycoproteins bind cell surface heparin sulfate proteoglycans (HSPGs) through
      heparin-binding domains. The G protein also has a CX3C chemokine motif which
      binds to the fractalkine receptor CX3CR1. G protein binding to CX3CR1 is not
      important for infection of immortalized cell lines, but reportedly is so for
      primary human airway epithelial cells (HAECs), the primary site for human
      infection. We studied the role of CX3CR1 in RSV infection with CX3CR1-transfected
      cell lines and HAECs with variable percentages of CX3CR1-expressing cells, and
      the effect of anti-CX3CR1 antibodies or a mutation in the RSV CX3C motif.
      Immortalized cells lacking HSPGs had low RSV binding and infection, which was
      increased markedly by CX3CR1 transfection. CX3CR1 was expressed primarily on
      ciliated cells, and ~50 % of RSV-infected cells in HAECs were CX3CR1+. HAECs with
      more CX3CR1-expressing cells had a proportional increase in RSV infection.
      Blocking G binding to CX3CR1 with anti-CX3CR1 antibody or a mutation in the CX3C
      motif significantly decreased RSV infection in HAECs. The kinetics of cytokine
      production suggested that the RSV/CX3CR1 interaction induced RANTES (regulated on
      activation normal T-cell expressed and secreted protein), IL-8 and fractalkine
      production, whilst it downregulated IL-15, IL1-RA and monocyte chemotactic
      protein-1. Thus, the RSV G protein/CX3CR1 interaction is likely important in
      infection and infection-induced responses of the airway epithelium, the primary
      site of human infection. 

PMID- 26297203
TI  - Acceptability of randomization to levonorgestrel versus copper intrauterine
      device among women requesting IUD insertion for contraception.
AB  - OBJECTIVE: Assess feasibility of randomizing women to intrauterine device (IUD)
      type. STUDY DESIGN: Women enrolling in a 2-month study who desired an IUD for
      contraception were randomized 1:1 to receive a levonorgestrel-releasing 52-mg IUD
      (LNG-IUD) or copper T380A IUD (Cu-IUD), understanding they could switch IUD type
      at the end of the study. RESULTS: Randomization to IUD type was acceptable to
      54/55 (98%) women who screened. All 32 enrolled participants completed follow-up.
      Two women exchanged their IUD (Cu-IUD to LNG-IUD), and two requested removal (one
      LNG-IUD, one Cu-IUD). Overall, 88% continued their assigned IUD. CONCLUSIONS:
      Randomization to IUD type is feasible, and few women change their IUD.

PMID- 26297205
TI  - Evaluating functional outcomes in adolescents with attention
      deficit/hyperactivity disorder: development and initial testing of a self-report
      instrument.
AB  - BACKGROUND: Engaging adolescents in decisions about their health may enhance
      their compliance with treatment and result in better health outcomes. Treatment
      outcomes in attention-deficit/hyperactivity disorder (ADHD) are rarely evaluated
      from the adolescents' point of view. There is also concern that adolescents with
      ADHD may not have insight about the impacts of their disease. This article
      describes research conducted to understand the experiences of adolescents with
      ADHD and how the research was used to develop an adolescent self-report
      instrument. METHODS: This research involved an iterative process to ensure
      content validity and was conducted in the following stages: concept
      identification from literature reviews and interviews with teachers and
      clinicians; concept elicitation interviews with adolescents with ADHD and their
      caregivers, review of existing instruments; development of a new instrument and
      cognitive interviews. Experts in instrument development and translation and
      clinical practitioners in ADHD also participated. RESULTS: A conceptual framework
      to measure the impact of ADHD on adolescent functioning identified from concept
      identification research informed concept elicitation interviews with 60
      adolescents with ADHD and their primary caregivers. In the interviews,
      adolescents discussed difficulties with performing activities in various
      contexts: school, home, leisure activities and social interactions. Caregivers
      provided additional insights. The instrument review revealed that none of the
      existing instruments were suitable to collect data on the elicited concepts;
      therefore, a new instrument was developed. Revisions were made to the format and
      content of the instrument (a daily diary) based on feedback received from
      cognitive testing with 15 adolescents. CONCLUSIONS: Our research helped to obtain
      a comprehensive understanding of the impacts of ADHD on adolescent functioning,
      to inform the development of a new instrument for measuring outcomes. Adolescents
      were able to discuss the impact of ADHD on their lives in concept elicitation
      interviews and report the impacts of ADHD on a self-report instrument. The new
      instrument developed to reflect the perspective of adolescents with ADHD can be
      used to supplement outcome assessments in clinic and research settings.
      Scientific advocacy for the use of such measures can be valuable to measure
      outcomes meaningful to adolescents with ADHD and the clinical community.

PMID- 26297206
TI  - Nanotechnology approaches for inhalation treatment of lung diseases.
AB  - Local administration of therapeutics by inhalation for treatment of lung diseases
      has the ability to deliver drugs, nucleic acids and peptides specifically to the
      site of their action and therefore enhance the efficacy of the treatment, limit
      the penetration of nebulized therapeutic agent(s) into the bloodstream and
      consequently decrease adverse systemic side effects of the treatment.
      Nanotechnology allows for a further enhancement of the treatment efficiency. The
      present review analyzes modern therapeutic approaches of inhaled nanoscale-based
      pharmaceutics for the detection and treatment of various lung diseases. 

PMID- 26297207
TI  - Inhibition of primary and metastatic tumors in mice by E-selectin-targeted
      polymer-drug conjugates.
AB  - There is currently no effective means to prevent or control metastatic
      dissemination of cancer cells. E-selectin, an adhesion molecule expressed
      exclusively on inflamed and angiogenic blood vessels, plays an important role in
      several rate-limiting steps of cancer metastasis. In this study, we assessed the
      in vivo antitumor efficacy of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers
      conjugated to an E-selectin binding peptide (Esbp, DITWDQLWDLMK) and equipped
      with the chemotherapeutic drug doxorubicin (P-(Esbp)-DOX) or with the
      proapoptotic peptide D(KLAKLAK)2 (P-(Esbp)-KLAK). Following a single intravenous
      injection, P-(Esbp)-DOX reduced tumor growth rate and prolonged the survival of
      mice bearing primary Lewis lung carcinoma (3LL) tumors significantly more than
      treatment with a non-targeted copolymer (P-DOX) or with free DOX. In an
      experimental B16-F10 lung metastasis model, a single intravenous dose of P-(Esbp)
      DOX or P-(Esbp)-KLAK prolonged mice survival time significantly more than the non
      targeted copolymers or the free drugs, and the percentage of complete tumor
      regression increased with increasing doses and with dosing frequency. In
      addition, mice pretreated with an E-selectin-targeted "drug-free" copolymer (P
      (Esbp)-FITC) exhibited significantly fewer B16-F10 tumor foci in the lungs as
      compared with non-treated mice, demonstrating the anti-metastatic properties of
      the copolymer and its ability to control cancer spread through E-selectin
      mediated interactions. Biodistribution analysis further confirmed the
      preferential accumulation of the E-selectin-targeted near-infrared fluorescently
      labeled copolymer P-(Esbp)-IR783 in B16-F10 lung metastases. Taken together, this
      study demonstrates, for the first time, that the E-selectin targeted copolymer
      drug conjugates can inhibit primary tumor growth and prevent metastases in vivo. 

PMID- 26297208
TI  - LL37 inhibits the inflammatory endothelial response induced by viral or
      endogenous DNA.
AB  - In viral infection, morbidity and mortality often result from extrahepatic
      disease manifestations such as vasculitis. We hereby show that human
      microvascular endothelial cells express viral receptors of the innate immune
      system which are induced upon ligand engagement. Furthermore, stimulation of
      endothelial cells with the synthetic analog of viral DNA, poly (dA:dT), human DNA
      and hepatitis B virus-containing immunoprecipitates from a patient with
      polyarteritis nodosa induces an inflammatory response including the upregulation
      of adhesion molecules, which is mediated exclusively by TLR9 and involves an IRF3
      dependent pathway. Thus, endothelial cells are able to actively participate in
      immune mediated vascular inflammation caused by viral infections. Furthermore, we
      provide evidence for the ability of LL37 to bind and internalize viral or
      endogenous DNA into non-immune cells. DNA nucleotides internalized by LL37
      suppress the production of proinflammatory mediators suggesting a protective
      effect against direct responses to viral infection or circulating DNA-fragments
      of endogenous origin. 

PMID- 26297209
TI  - Shear-Wave Elastography for the Detection of Residual Breast Cancer After
      Neoadjuvant Chemotherapy.
AB  - OBJECTIVE: This study was designed to evaluate the accuracy of shear-wave
      elastography (SWE) in the detection of residual breast cancer after neoadjuvant
      chemotherapy (NAC). METHODS: Seventy-one women with stage II-III breast cancers
      who underwent B-mode ultrasound (US), SWE, and magnetic resonance imaging (MRI)
      after NAC were included. The presence of residual cancer was determined on B-mode
      US and MRI, and the maximum elasticity of residual lesions was assessed on SWE.
      The sensitivity, specificity, accuracy, and area under the receiver operating
      characteristic curve (AUC) of B-mode US, SWE, and MRI were compared. RESULTS:
      Sixty-one of 71 women (86 %) had residual cancer and showed higher maximum
      elasticity values (mean 116.0 +/- 74.1 kPa) than those without residual cancer
      (26.4 +/- 21.0 kPa; p < 0.001). B-mode US showed 72.1 % (44/61) sensitivity, 50.0
      % (5/10) specificity, and 69.0 % (49/71) accuracy. The sensitivity, specificity,
      and accuracy of SWE were 83.6 % (51/61), 80.0 % (8/10), and 83.1 % (59/71) when a
      maximum elasticity value of >30 kPa was considered to indicate the presence of
      residual cancer. The combined AUC of B-mode US and SWE (0.877) was significantly
      higher than that of B-mode US (0.702) (p = 0.014) and comparable to that of MRI
      (0.939) (p = 0.147). CONCLUSIONS: SWE allowed relatively accurate assessment for
      the presence of residual lesion after NAC and improved the diagnostic performance
      of B-mode US.

PMID- 26297204
TI  - Lung cancer: Biology and treatment options.
AB  - Lung cancer remains the leading cause of cancer mortality in men and women in the
      U.S. and worldwide. About 90% of lung cancer cases are caused by smoking and the
      use of tobacco products. However, other factors such as radon gas, asbestos, air
      pollution exposures, and chronic infections can contribute to lung
      carcinogenesis. In addition, multiple inherited and acquired mechanisms of
      susceptibility to lung cancer have been proposed. Lung cancer is divided into two
      broad histologic classes, which grow and spread differently: small-cell lung
      carcinomas (SCLCs) and non-small cell lung carcinomas (NSCLCs). Treatment options
      for lung cancer include surgery, radiation therapy, chemotherapy, and targeted
      therapy. Therapeutic-modalities recommendations depend on several factors,
      including the type and stage of cancer. Despite the improvements in diagnosis and
      therapy made during the past 25 years, the prognosis for patients with lung
      cancer is still unsatisfactory. The responses to current standard therapies are
      poor except for the most localized cancers. However, a better understanding of
      the biology pertinent to these challenging malignancies, might lead to the
      development of more efficacious and perhaps more specific drugs. The purpose of
      this review is to summarize the recent developments in lung cancer biology and
      its therapeutic strategies, and discuss the latest treatment advances including
      therapies currently under clinical investigation.

PMID- 26297210
TI  - The thyrohyoid membrane as a target for ultrasonography-guided block of the
      internal branch of the superior laryngeal nerve.
AB  - STUDY OBJECTIVE: The objective was to present a proof of concept for a simple and
      consistently successful ultrasonograpy (US)-guided technique to block the
      internal branch of the superior laryngeal nerve (iSLN). DESIGN: This was a
      volunteer and cadaver anatomy study. SETTING: The setting was an anesthesiology
      department and an anatomy laboratory at a medical school MEASUREMENTS: H13-6 MHz
      US scans were performed in 40 healthy volunteers positioned supine and with
      extended necks. The goals were to identify the thyrohyoid membrane, measure its
      depth (in centimeters) using the shortest vertical distance from the skin, and
      record the scanning time (in seconds) needed to obtain the optimal image.
      Anatomical dissection was performed with an operating microscope bilaterally on 5
      adult cadaver heads, fixed in formalin, to expose the point of iSLN penetration
      through the thyrohyoid membrane. The distance between the greater horn of the
      hyoid bone and the nerve entry point into the thyrohyoid membrane was measured.
      Ultrasonography-guided in-plane injections were performed unilaterally with 22
      gauge 50-mm nerve block needles in 3 fresh cadavers with 2-mL lidocaine/methylene
      blue mixture deposited under direct vision just superficial to the thyrohyoid
      membrane to evaluate technical feasibility and injectate spread. MAIN RESULTS:
      Anatomically, the iSLN was identified in all formalin-preserved cadavers, with
      hyoid bone greater horn to nerve-membrane interface distances measuring 1.0-2.4
      cm (mean, 2.0 cm; SD, 0.5). Sonographically, the iSLN was not visualized, whereas
      the hyoid bone and the thyrohyoid membrane were visualized in all volunteers. The
      mean distance from skin to thyrohyoid membrane was 1.69 cm (SD, 0.38). The mean
      time needed to scan was 15 seconds (SD, 2.3). After US-guided injection, the dye
      deposition was observed around the iSLN in all cadaver specimens. CONCLUSIONS: A
      simpler and consistently reproducible US-guided iSLN block is feasible using the
      thyrohyoid membrane as target plane for local anesthetic injection. Clinical
      trials are needed to determine its effectiveness and safety, needle entry point,
      trajectory, and local anesthetic volume.

PMID- 26297211
TI  - A clear cell variant of mucoepidermoid carcinoma harboring CRTC1-MAML2 fusion
      gene found in buccal mucosa: report of a case showing a large clear cell
      component and lacking typical epidermoid cells and intermediate cells.
AB  - The predominance of clear cells in mucoepidermoid carcinomas (MEC) is rare, and
      cases in which this occurs are termed clear cell variants of MEC. We present a
      case of a 70-year-old woman complaining of a right buccal mucosal mass, which had
      increased in size over 1 year. Histological examination revealed the mass to be
      composed predominantly of clear tumor cells, with mucin-containing cells and
      intermediate cell-like cells. Immunohistochemistry indicated that the tumor was
      positive for CK5/6 and p63, but negative for myoepithelial markers such as S-100
      protein, alphaSMA, and calponin. These findings ruled out the possibility of a
      clear cell myoepithelial carcinoma, which is the most frequently observed type of
      salivary carcinoma composed predominantly of clear cells. However, it is
      difficult to distinguish between clear cell variants of MEC and hyalinizing clear
      cell carcinoma. Therefore, we performed fluorescence in situ hybridization to
      determine whether MAML2 rearrangement had occurred in this mass. Direct
      sequencing of the RT-PCR product demonstrated CRTC1-MAML2 fusion between exon 1
      of CRTC1 and exon 2 of MAML2. Thus, the diagnosis of clear cell variant of MEC
      was confirmed. This is the first report of CRTC1-MAML2 fusion gene detection in a
      clear cell variant of MEC.

PMID- 26297212
TI  - Improving the molecular diagnosis of Chlamydia psittaci and Chlamydia abortus
      infection with a species-specific duplex real-time PCR.
AB  - Chlamydia psittaci and Chlamydia abortus are closely related intracellular
      bacteria exhibiting different tissue tropism that may cause severe but distinct
      infection in humans. C. psittaci causes psittacosis, a respiratory zoonotic
      infection transmitted by birds. C. abortus is an abortigenic agent in small
      ruminants, which can also colonize the human placenta and lead to foetal death
      and miscarriage. Infections caused by C. psittaci and C. abortus are
      underestimated mainly due to diagnosis difficulties resulting from their strict
      intracellular growth. We developed a duplex real-time PCR to detect and
      distinguish these two bacteria in clinical samples. The first PCR (PCR1) targeted
      a sequence of the 16S-23S rRNA operon allowing the detection of both C. psittaci
      and C. abortus. The second PCR (PCR2) targeted the coding DNA sequence CPSIT_0607
      unique to C. psittaci. The two PCRs showed 100 % detection for >= 10 DNA copies
      per reaction (1000 copies ml(- 1)). Using a set of 120 samples, including
      bacterial reference strains, clinical specimens and infected cell culture
      material, we monitored 100 % sensitivity and 100 % specificity for the detection
      of C. psittaci and C. abortus for PCR1. When PCR1 was positive, PCR2 could
      discriminate C. psittaci from C. abortus with a positive predictive value of 100
      % and a negative predictive value of 88 %. In conclusion, this new duplex PCR
      represents a low-cost and time-saving method with high-throughput potential,
      expected to improve the routine diagnosis of psittacosis and pregnancy
      complication in large-scale screening programs and also during outbreaks.

PMID- 26297213
TI  - Healthy Living: The European Congress of Epidemiology, 2015.

PMID- 26297215
TI  - Metformin-associated lactic acidosis: time to let it go?

PMID- 26297214
TI  - Associations between early body mass index trajectories and later metabolic risk
      factors in European children: the IDEFICS study.
AB  - Faster growth seems to be a common factor in several hypotheses relating early
      life exposures to subsequent health. This study aims to investigate the
      association between body mass index (BMI) trajectories during infancy/childhood
      and later metabolic risk in order to identify sensitive periods of growth
      affecting health. In a first step, BMI trajectories of 3301 European children
      that participated in the multi-centre Identification and Prevention of Dietary
      and Lifestyle-induced Health Effects in Children and Infants (IDEFICS) study were
      modelled using linear-spline mixed-effects models. The estimated random
      coefficients indicating initial subject-specific BMI and rates of change in BMI
      over time were used as exposure variables in a second step and related to a
      metabolic syndrome (MetS) score and its single components based on conditional
      regression models (mean age at outcome assessment: 8.5 years). All exposures
      under investigation, i.e. BMI at birth, rates of BMI change during infancy (0 to
      <9 months), early childhood (9 months to <6 years) and later childhood (>=6
      years) as well as current BMI z-score were significantly associated with the
      later MetS score. Associations were strongest for the rate of BMI change in early
      childhood (1.78 [1.66; 1.90]; beta estimate and 99 % confidence interval) and
      current BMI z-score (1.16 [0.96; 1.38]) and less pronounced for BMI at birth
      (0.62 [0.47; 0.78]). Results slightly differed with regard to the single
      metabolic factors. Starting from birth rapid BMI growth, especially in the time
      window of 9 months to <6 years, is significantly related to later metabolic risk
      in children. Much of the associations of early BMI growth may further be mediated
      through the effects on subsequent BMI growth.

PMID- 26297216
TI  - Glycated human serum albumin induces NF-kappaB activation and endothelial nitric
      oxide synthase uncoupling in human umbilical vein endothelial cells.
AB  - AIMS: Non-enzymatic glycated proteins could mediate diabetes vascular
      complications, but the molecular mechanisms are unknown. Our objective was to
      find new targets involved in the glycated human serum albumin (gHSA)-enhanced
      extracellular reactive oxygen species (ROS) production in human endothelial
      cells. METHODS & RESULTS: Some nuclear factors and phosphorylation cascades were
      analysed. gHSA activated nuclear factor kappa-light-chain-enhancer of activated B
      cells (NF-kappaB), which up-regulated NOX4 and P22PHOX and enhanced ROS
      production. Pharmacological inhibition of NF-kappaB reversed gHSA-enhanced NOX4
      expression and decreased gHSA-induced ROS production in extra- and intracellular
      spaces. The inhibition of activator protein-1 (AP-1) induced a rise in NOX4 and
      P22PHOX subunit expression and a down-regulation of endothelial nitric oxide
      synthase (eNOS). AP-1 inhibition also enhanced extracellular ROS production in
      the presence of serum albumin, but not with gHSA. These results were explained by
      the eNOS uncoupling induced by gHSA, also demonstrated in this study.
      Phosphatidylinositol 3-kinase or mitogen-activated protein kinase kinase 1/2 did
      not show to be involved in gHSA-induced ROS production. CONCLUSIONS: All
      together, the results suggested that gHSA-enhanced ROS production in endothelium
      is mediated by: 1) NF-kappaB activation and subsequence up-regulation of NADPH
      oxidase, 2) eNOS uncoupling. AP-1, although is not directly affected by gHSA, is
      another target for regulating NADPH oxidase and eNOS expression in endothelial
      cells.

PMID- 26297217
TI  - The renoprotective role of autophagy activation in proximal tubular epithelial
      cells in diabetic nephropathy.
AB  - With intensive investigations recently, autophagy is hoped to be a potential
      therapeutic target to prevent or alleviate diabetic nephropathy (DN). Our
      previous study revealed that lipotoxicity participated in epithelial-to
      mesenchymal transition (EMT) of proximal tubular epithelial cells (PTECs) under
      diabetic conditions. Based on evidences that autophagy and lipid metabolism are
      closely related, we investigated autophagy under diabetic conditions and how it
      contributed in the lipotoxicity and EMT. In high-glucose-cultured PTECs, we found
      that Beclin1 and LC3-II were elevated, while p62 was decreased. These results
      indicate that autophagy activity was elevated under diabetic conditions.
      Autophagy deficiency induced by autophagy inhibitors, chloroquine diphosphate
      (CQ) and 3-Methyladenine (3-MA), and by Atg5 siRNA transfection exacerbated lipid
      accumulation and EMT. This supports that the elevated autophagy activity acts as
      a renoprotective response under diabetic conditions. Treatment of rapamycin,
      which is a mammalian target of rapamycin (mTOR) receptor-specific inhibitor and a
      known autophagy activator, attenuated high-glucose-induced lipid accumulation and
      EMT. The Atg5 silence counteracted the protective effect of rapamycin. The
      present study deepens our understanding of the role of autophagy in DN,
      suggesting a complex interplay of autophagy, metabolic pathways, lipotoxicity and
      EMT.

PMID- 26297218
TI  - An association of large-fibre peripheral nerve dysfunction with non-invasive
      measures of liver fibrosis secondary to non-alcoholic fatty liver disease in
      diabetes.
AB  - AIM: To examine for an association of elevated lower-limb vibration perception
      threshold (VPT) with NAFLD fibrosis. METHODS: Two cohorts from a tertiary
      diabetes centre were studied - Cohort 1, n=456 with type 1 or 2 diabetes, and
      Cohort 2, n=106 with type 2 diabetes mellitus. All underwent a detailed
      assessment, including VPT measurement. Cohort 2 also had liver ultrasound and
      transient elastography (TE). NAFLD Fibrosis Score (NFS) was calculated for all
      with available data. Follow-up VPT measurements on participants in Cohort 1 to
      2014 were also collected if available. RESULTS: Adjusted risk of higher VPT
      category (>=25V but <50V, or >=50V, c.f. < 25V) was greater for high-risk NFS in
      both cohorts (Cohort 1, OR 2.22 [95% CI 1.24-3.98, p=0.007] and Cohort 2, OR 4.51
      [95% CI 1.08-18.87], p=0.039) and higher liver stiffness measurement (LSM) by TE
      in Cohort 2 (OR for each unit natural log increase in LSM of 2.42 (95% CI 1.13
      5.19), p=0.023). In Cohort 1, in those with VPT<50V and complete data, those with
      higher NFS had greater odds of increasing VPT category after 2.2 (IQR 1.5-2.9)
      years. CONCLUSIONS: Higher VPT associates with markers of liver fibrosis due to
      NAFLD in diabetes mellitus.

PMID- 26297219
TI  - Pedobacter nanyangensis sp. nov., isolated from herbicide-contaminated soil.
AB  - A Gram-stain-negative, strictly aerobic, non-spore-forming, motile, rod-shaped
      bacterium, designated Q-4T, was isolated from a herbicide-contaminated soil
      sample in Nanyang, Henan province, China. Strain Q-4T grew optimally in the LB
      medium without NaCl supplement at a pH range of 6.0-7.0 and a temperature of 30 
      degrees C. Phylogenetic analysis based on 16S rRNA gene sequences showed that
      strain Q-4T was most closely related to 'Pedobacter zeaxanthinifaciens' TDMA-5
      (97.4 % 16S rRNA gene sequence similarity), followed by Pedobacter xixiisoli S27T
      (95.8 %). The genomic DNA G+C content of strain Q-4T was 41.8 mol%. MK-7 was the
      major respiratory quinone. Phosphatidylethanolamine and phosphoaminolipid were
      the major polar lipids. The major fatty acids were iso-C15 : 0, iso-C17 : 0 3-OH,
      C16 : 1omega6c and/or C16 : 1omega7c (summed feature 3) and C16 : 1omega7c/C16 :
      1omega6c (summed feature 3). Strain Q-4T showed low DNA-DNA relatedness with 'P.
      zeaxanthinifaciens' TDMA-5 (21.4 +/- 0.6 %). Physiological and biochemical
      characteristics are able to distinguish strain Q-4T from the most closely related
      species of the genus Pedobacter. On the basis of genotypic and phenotypic data,
      strain Q-4T is considered to represent a novel species of the genus Pedobacter,
      for which the name Pedobacter nanyangensis sp. nov. is proposed. The type strain
      is Q-4T ( = KCTC 42442T = ACCC 19798T).

PMID- 26297220
TI  - Lewinella xylanilytica sp. nov., a member of the family Saprospiraceae isolated
      from coastal seawater.
AB  - An orange-pigmented bacterium, designated strain 13-9-B8T, was isolated from a
      seawater sample collected at Marado, Jeju Island, South Korea. The novel strain
      was Gram-staining-negative, non-motile, non-gliding, rod-shaped and aerobic. A
      phylogenetic analysis based on 16S rRNA gene sequences revealed that the strain
      clustered with members of the genus Lewinella of the family Saprospiraceae in the
      phylum Bacteroidetes and was most closely related to the species Lewinella marina
      (95.6 % similarity to the type strain). Strain 13-9-B8T grew optimally at 30 
      degrees C, pH 7.0 and with 2 % (w/v) NaCl. Strain 13-9-B8T contained MK-7 as the
      predominant menquinone and summed feature 3, iso-C15 : 0 and iso-C17 : 0 3-OH as
      the major fatty acids. The polar lipids detected in strain 13-9-B8T were
      phosphatidylethanolamine, one unidentified aminolipid, one unidentified
      phospholipid and eight unidentified lipids. The DNA G+C content of strain 13-9
      B8T was 59.1 mol%. Based on phenotypic, chemotaxonomic and phylogenetic data
      presented, strain 13-9-B8T is considered to represent a novel species of the
      genus Lewinella, for which the name Lewinella xylanilytica sp. nov. is proposed.
      The type strain is 13-9-B8T ( = DSM 29526T = KCTC 32663T). 

PMID- 26297221
TI  - Five-minute Apgar score and educational outcomes: retrospective cohort study of
      751,369 children.
AB  - BACKGROUND: The Apgar score is used worldwide for assessing the clinical
      condition and short-term prognosis of newborn infants. Evidence for a
      relationship with long-term educational outcomes is conflicting. We investigated
      whether Apgar score at 5 min after birth was associated with additional support
      needs (ASN) and educational attainment. METHODS: Data on pregnancy, delivery and
      later educational outcomes for children attending Scottish schools between 2006
      and 2011 were collated by linking individual-level data from national educational
      and maternity databases. The relationship between Apgar score and overall ASN,
      type-specific ASN and educational attainment was assessed using binary,
      multinomial and generalised ordinal logistic regression models, respectively.
      Missing covariate data were imputed. RESULTS: Of the 751,369 children eligible,
      9741 (1.3%) had a low or intermediate Apgar score and 49,962 (6.6%) had ASN. Low
      Apgar score was independently associated with overall ASN status (adjusted OR for
      Apgar <=3, OR 1.52 95% CI 1.35 to 1.70), as well as ASN due to cognitive (OR
      1.26, 95% CI 1.09 to 1.47), sensory (OR 2.49 95% CI 1.66 to 3.73) and motor (OR
      3.57, 95% CI 2.86 to 4.47) impairments. There was a dose-response relationship
      between Apgar score and overall ASN status: of those scoring 0-3, 10.1% had ASN,
      compared with 9.1% of those scoring 4-7 and 6.6% of those scoring 7-10. A low
      Apgar score was associated with lower educational attainment, but this was not
      robust to adjustment for confounders. CONCLUSIONS: Apgar scores are associated
      with long-term as well as short-term prognoses, and with educational as well as
      clinical outcomes at the population level.

PMID- 26297222
TI  - Effects of an evidence-based computerized virtual clinician on low-density
      lipoprotein and non-high-density lipoprotein cholesterol in adults without
      cardiovascular disease: The Interactive Cholesterol Advisory Tool.
AB  - There is a lack of research on the use of electronic tools that guide patients
      toward reducing their cardiovascular disease risk. We conducted a 9-month
      clinical trial in which participants who were at low (n = 100) and moderate (n =
      23) cardiovascular disease risk-based on the National Cholesterol Education
      Program III's 10-year risk estimator-were randomized to usual care or to usual
      care plus use of an Interactive Cholesterol Advisory Tool during the first 8
      weeks of the study. In the moderate-risk category, an interaction between
      treatment condition and Framingham risk estimate on low-density lipoprotein and
      non-high-density lipoprotein cholesterol was observed, such that participants in
      the virtual clinician treatment condition had a larger reduction in low-density
      lipoprotein and non-high-density lipoprotein cholesterol as their Framingham risk
      estimate increased. Perceptions of the Interactive Cholesterol Advisory Tool were
      positive. Evidence-based information about cardiovascular disease risk and its
      management was accessible to participants without major technical challenges.

PMID- 26297223
TI  - Plasma levels of microRNA-24, microRNA-320a, and microRNA-423-5p are potential
      biomarkers for colorectal carcinoma.
AB  - BACKGROUND: MicroRNAs are stable and easy to detect in plasma. The plasma levels
      of microRNAs are often changed in disease conditions, including cancer. This
      makes circulating microRNAs a novel class of biomarkers for cancer diagnosis.
      Analyses of online microRNA data base revealed that expression level of three
      microRNAs, microRNA-24 (miR-24), microRNA-320a (miR-320a), and microRNA-423-5p
      (miR-423-5p) were down-regulated in colorectal cancer (CRC). However, whether the
      plasma level of these three microRNAs can serve as biomarkers for CRC diagnosis
      and prognosis is not determined. METHODS: Plasma samples from 223 patients with
      colorectal related diseases (111 cancer carcinoma, 59 adenoma, 24 colorectal
      polyps and 29 inflammatory bowel disease) and 130 healthy controls were collected
      and subjected to reverse transcription-quantitative real time PCR (RT-qPCR)
      analyses for the three microRNAs. In addition, plasma samples from 43 patients
      were collected before and after surgical treatment for the same RT-qPCR analyses.
      RESULTS: The concentrations of plasma miR-24, miR-320a and miR-423-5p were all
      decreased in patients with CRC and benign lesions (polyps and adenoma) compared
      with healthy controls, but increased in inflammatory bowel disease (IBD). The
      sensitivity of miR-24, miR-320a and miR-423-5p for early stage of CRC were 77.78
      %, 90.74 %, and 88.89 %, respectively. Moreover, the plasma concentration of the
      three microRNAs was increased in patients after the surgery who had clinical
      improvement. CONCLUSIONS: The plasma levels of miR-24, miR-320a, and miR-423-5p
      have promising potential to serve as novel biomarkers for CRC detection,
      especially for early stage of CRC, which are superior to the currently used
      clinical biomarkers for CRC detection, such as CEA and CA19-9. Further efforts to
      develop the three microRNAs as biomarkers for early CRC diagnosis and prediction
      of surgical treatment outcomes are warrant.

PMID- 26297225
TI  - Vascular endothelial cell membranes differentiate between stretch and shear
      stress through transitions in their lipid phases.
AB  - Vascular endothelial cells (ECs) respond to the hemodynamic forces stretch and
      shear stress by altering their morphology, functions, and gene expression.
      However, how they sense and differentiate between these two forces has remained
      unknown. Here we report that the plasma membrane itself differentiates between
      stretch and shear stress by undergoing transitions in its lipid phases. Uniaxial
      stretching and hypotonic swelling increased the lipid order of human pulmonary
      artery EC plasma membranes, thereby causing a transition from the liquid
      disordered phase to the liquid-ordered phase in some areas, along with a decrease
      in membrane fluidity. In contrast, shear stress decreased the membrane lipid
      order and increased membrane fluidity. A similar increase in lipid order occurred
      when the artificial lipid bilayer membranes of giant unilamellar vesicles were
      stretched by hypotonic swelling, indicating that this is a physical phenomenon.
      The cholesterol content of EC plasma membranes significantly increased in
      response to stretch but clearly decreased in response to shear stress. Blocking
      these changes in the membrane lipid order by depleting membrane cholesterol with
      methyl-beta-cyclodextrin or by adding cholesterol resulted in a marked inhibition
      of the EC response specific to stretch and shear stress, i.e., phosphorylation of
      PDGF receptors and phosphorylation of VEGF receptors, respectively. These
      findings indicate that EC plasma membranes differently respond to stretch and
      shear stress by changing their lipid order, fluidity, and cholesterol content in
      opposite directions and that these changes in membrane physical properties are
      involved in the mechanotransduction that activates membrane receptors specific to
      each force. 

PMID- 26297224
TI  - Impaired compensation to femoral artery ligation in diet-induced obese mice is
      primarily mediated via suppression of collateral growth by Nox2 and p47phox.
AB  - The present study was undertaken to establish the role of NADPH oxidase (Nox) in
      impaired vascular compensation to arterial occlusion that occurs in the presence
      of risk factors associated with oxidative stress. Diet-induced obese (DIO) mice
      characterized by multiple comorbidities including diabetes and hyperlipidemia
      were used as a preclinical model. Arterial occlusion was induced by distal
      femoral artery ligation in lean and DIO mice. Proximal collateral arteries were
      identified as the site of major (~70%) vascular resistance to calf perfusion by
      distal arterial pressures, which decreased from ~80 to ~30 mmHg with ligation in
      both lean and DIO mice. Two weeks after ligation, significant vascular
      compensation occurred in lean but not DIO mice as evidenced by increased
      perfusion (147 +/- 48% vs. 49 +/- 29%) and collateral diameter (151 +/- 30% vs.
      44 +/- 17%). Vascular mRNA expression of p22(phox), Nox2, Nox4, and p47(phox)
      were all increased in DIO mice. Treatment of DIO mice with either apocynin or
      Nox2ds-tat or with whole body ablation of either Nox2 or p47(phox) ameliorated
      the impairment in both collateral growth and hindlimb perfusion. Multiparametric
      flow cytometry analysis demonstrated elevated levels of circulating monocytes in
      DIO mice without impaired mobilization and demargination after femoral artery
      ligation. These results establish collateral resistance as the major limitation
      to calf perfusion in this preclinical model, demonstrate than monocyte
      mobilization and demarginatin is not suppressed, implicate Nox2-p47(phox)
      interactions in the impairment of vascular compensation to arterial occlusion in
      DIO mice, and suggest that selective Nox component suppression/inhibition may be
      effective as either primary or adjuvant therapy for claudicants. 

PMID- 26297226
TI  - Relationship of hyperuricemia with mortality in heart failure patients with
      preserved ejection fraction.
AB  - Serum uric acid is a predictor of cardiovascular mortality in heart failure with
      reduced ejection fraction. However, the impact of uric acid on heart failure with
      preserved ejection fraction (HFpEF) remains unclear. Here, we investigated the
      association between hyperuricemia and mortality in HFpEF patients. Consecutive
      424 patients, who were admitted to our hospital for decompensated heart failure
      and diagnosed as having HFpEF, were divided into two groups based on presence of
      hyperuricemia (serum uric acid >=7 mg/dl or taking antihyperuricemic agents). We
      compared patient characteristics, echocardiographic data, cardio-ankle vascular
      index, and cardiopulmonary exercise test findings between the two groups and
      prospectively followed cardiac and all-cause mortality. Compared with the non
      hyperuricemia group (n = 170), the hyperuricemia group (n = 254) had a higher
      prevalence of hypertension (P = 0.013), diabetes mellitus (P = 0.01),
      dyslipidemia (P = 0.038), atrial fibrillation (P = 0.001), and use of diuretics
      (P < 0.001). Cardio-ankle vascular index (8.7 vs. 7.5, P < 0.001) and Ve/Vco2
      slope (34.9 vs. 31.9, P = 0.02) were also higher. In addition, peak Vo2 (14.9 vs.
      17.9 ml.kg(-1).min(-1), P < 0.001) was lower. In the follow-up period (mean 897
      days), cardiac and all-cause mortalities were significantly higher in those with
      hyperuricemia (P = 0.006 and P = 0.004, respectively). In the multivariable Cox
      proportional hazard analyses after adjustment for several confounding factors
      including chronic kidney disease and use of diuretics, hyperuricemia was an
      independent predictor of all-cause mortality (hazard ratio 1.98, 95% confidence
      interval 1.036-3.793, P = 0.039). Hyperuricemia is associated with arterial
      stiffness, impaired exercise capacity, and high mortality in HFpEF. 

PMID- 26297227
TI  - Even is better than odd: one fat may conceal another.

PMID- 26297228
TI  - Can ErbB2 overexpression protect against doxorubicin cardiotoxicity?

PMID- 26297229
TI  - Manipulation of KCNE2 expression modulates action potential duration and Ito and
      IK in rat and mouse ventricular myocytes.
AB  - In heterologous expression systems, KCNE2 has been demonstrated to interact with
      multiple alpha-subunits of voltage-dependent cation channels and modulate their
      functions. However, the physiological and pathological roles of KCNE2 in
      cardiomyocytes are poorly understood. The present study aimed to investigate the
      effects of bidirectional modulation of KCNE2 expression on action potential (AP)
      duration (APD) and voltage-dependent K(+) channels in cardiomyocytes. Adenoviral
      gene delivery and RNA interference were used to either increase or decrease KCNE2
      expression in cultured neonatal and adult rat or neonatal mouse ventricular
      myocytes. Knockdown of KCNE2 prolonged APD in both neonatal and adult myocytes,
      whereas overexpression of KCNE2 shortened APD in neonatal but not adult myocytes.
      Consistent with the alterations in APD, KCNE2 knockdown decreased transient
      outward K(+) current (Ito) densities in neonatal and adult myocytes, whereas
      KCNE2 overexpression increased Ito densities in neonatal but not adult myocytes.
      Furthermore, KCNE2 knockdown accelerated the rates of Ito activation and
      inactivation, whereas KCNE2 overexpression slowed Ito gating kinetics in neonatal
      but not adult myocytes. Delayed rectifier K(+) current densities were remarkably
      affected by manipulation of KCNE2 expression in mouse but not rat cardiomyocytes.
      Simulation of the AP of a rat ventricular myocyte with a mathematical model
      showed that alterations in Ito densities and gating properties can result in
      similar APD alterations in KCNE2 overexpression and knockdown cells. In
      conclusion, endogenous KCNE2 in cardiomyocytes is important in maintaining
      cardiac electrical stability mainly by regulating Ito and APD. Perturbation of
      KCNE2 expression may predispose the heart to ventricular arrhythmia by prolonging
      APD. 

PMID- 26297230
TI  - Small-conductance Ca2+-activated K+ current is upregulated via the
      phosphorylation of CaMKII in cardiac hypertrophy from spontaneously hypertensive
      rats.
AB  - Left ventricular hypertrophy is associated with an increased risk of ventricular
      arrhythmias. However, the underlying molecular basis is poorly understood. It has
      been reported that small-conductance Ca(2+)-activated K(+) (SK) channels are
      involved in the pathogenesis of ventricular arrhythmias in heart failure. The
      present study aimed to test the hypothesis that SK channel activity is increased
      via the Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)-dependent pathway
      in hypertensive cardiac hypertrophy. Normotensive Wistar-Kyoto (WKY) rats and
      spontaneous hypertensive rats (SHRs) were used. Whole cell membrane currents were
      recorded in isolated ventricular myocytes by the patch-clamp method, and apamin
      sensitive K(+) current (IKAS), which is inhibited by apamin (100 nM), an SK
      channel blocker, was evaluated. IKAS at 40 mV was present in SHRs, whereas it was
      hardly detectable in WKY rats (0.579 +/- 0.046 vs. 0.022 +/- 0.062 pA/pF, both n
      = 6, P < 0.05). IKAS was almost completely abolished by 1 MUM KN-93, a CaMKII
      inhibitor, in SHRs. Optical recordings of left ventricular anterior wall action
      potentials revealed that apamin prolonged the late phase of repolarization only
      in SHRs. Western blot analysis of SK channel protein isoforms demonstrated that
      SK2 was significantly increased in SHRs compared with WKY rats (SK2/GAPDH: 0.66
      +/- 0.07 vs. 0.40 +/- 0.02, both n = 6, P < 0.05), whereas SK1 and SK3 did not
      differ between groups. In addition, autophosphorylated CaMKII was significantly
      increased in SHRs (phosphorylated CaMKII/GAPDH: 0.80 +/- 0.06 vs. 0.58 +/- 0.06,
      both n = 6, P < 0.05) despite a comparable total amount of CaMKII between groups.
      In conclusion, SK channels are upregulated via the enhanced activation of CaMKII
      in cardiac hypertrophy in SHRs. 

PMID- 26297231
TI  - Celeribacter naphthalenivorans sp. nov., a naphthalene-degrading bacterium from
      tidal flat sediment.
AB  - A Gram-stain-negative, aerobic and moderately halophilic bacterium, designated
      strain EMB201(T), was isolated from tidal flat sediment of the South Sea in
      Korea. Cells were motile rods with a single polar flagellum and had catalase- and
      oxidase-positive activities. Growth of strain EMB201(T) was observed at 15-37 
      degrees C (optimum, 30  degrees C), at pH 5.0-9.5 (optimum, pH 7.0-7.5) and in
      the presence of 1-7% (w/v) NaCl (optimum, 2-3%). Strain EMB201(T) contained
      ubiquinone-10 as the sole isoprenoid quinone and summed feature 8 (comprising C18
      : 1omega7c/omega6c), C18 : 0omega7c 11-methyl and C10 : 0 3-OH as the major fatty
      acids. Phosphatidylglycerol and an unidentified amino lipid were identified as
      the major polar lipids and an unidentified phospholipid and three unidentified
      lipids were detected as minor components. The G+C content of the genomic DNA was
      approximately 58.4 mol%. Phylogenetic analysis based on 16S rRNA gene sequences
      showed that strain EMB201(T) formed a phylogenetic lineage with members of the
      genus Celeribacter. Strain EMB201(T) was related most closely to Celeribacter
      halophilus ZXM137(T) with a 16S rRNA gene sequence similarity of 98.3%, and the
      level of DNA-DNA relatedness between the two strains was 17.0 +/- 2.0%. The
      combined chemotaxonomic and molecular properties suggest that strain EMB201(T)
      represents a novel species of the genus Celeribacter, for which the name
      Celeribacter naphthalenivorans sp. nov. is proposed. The type strain is EMB201(T)
      ( = KACC 18393(T) = JCM 30679(T)).

PMID- 26297233
TI  - Reclassification of Acetomicrobium faecale as Caldicoprobacter faecalis comb.
      nov.
AB  - Taking into account its phenotypical and genetic characteristics, Acetomicrobium
      faecale was first recognized as a member of the genus Acetomicrobium, family
      Bacteroidaceae, order Bacteroidales, phylum Bacteroidetes, with Acetomicrobium
      flavidum the type species of the genus. However, it was found that A. faecale had
      95.8 %, 97.6 % and 98.4 % similarity, respectively, with Caldicoprobacter
      guelmensis, Caldicoprobacter algeriensis and Caldicoprobacter oshimai and only 82
      % similarity with A. flavidum. The DNA G+C content of A. faecale is 45 mol ,
      which is of the same order as the DNA G+C content of the three strains of species
      of the genus Caldicoprobacter and its main fatty acid is C16 : 0, with its second
      most prominent fatty acid, iso-C17 : 0, also common to strains of species of the
      genus Caldicoprobacter. On the basis of further phylogenetic, genetic and
      chemotaxonomic studies, we propose that A. faecale (type strain DSM 20678T = JCM
      30420T) be reclassified as Caldicoprobacter faecalis comb. nov. 

PMID- 26297232
TI  - Patient and practitioners' views on the most important outcomes arising from
      primary care consultations: a qualitative study.
AB  - BACKGROUND: Primary care clinicians often address multiple patient problems, with
      a range of possible outcomes. There is currently no patient-reported outcome
      measure (PROM) which covers this range of outcomes. Consequently, many
      researchers use PROMs that do not capture the full impact of primary care
      services. In order to identify what outcomes a PROM for primary care would need
      to include, we conducted interviews with patients and practitioners. This paper
      reports these patient and practitioners' views on the outcomes arising from
      primary care consultations. METHODS: Semi-structured interviews were held with 30
      patients and eight clinicians across five sites in Bristol. Interviews were audio
      recorded, transcribed and analysed thematically. We used a broad definition of
      health outcome as 'the impacts of healthcare on health, or a patient's ability to
      impact health' to identify outcomes through this process. RESULTS: 10 outcome
      groups were identified. These occupied 3 domains: Health Empowerment: These are
      the internal and external resources which enable patients to improve their
      health. This involves 1) patients' understanding of their illnesses, 2) ability
      to self-care and stay healthy, 3) agreeing and adhering to a patient-clinician
      shared plan, 4) confidence in seeking healthcare and 5) access to support. Health
      Status: This involves 6) reduction of symptoms and 7) reducing the impact of
      symptoms on patients' lives. Health Perceptions: This involves 8) patients'
      satisfaction with their health, 9) health concerns, and 10) confidence in their
      future health. The structure, organisation and nature of primary care means it
      can affect all 3 domains. CONCLUSIONS: No existing PROM captures all these
      outcomes. For example, many health empowerment PROMs do not consider patient
      preference on empowerment. Many health status tools are not responsive to changes
      resulting from primary care. Health perceptions PROMs have generally been
      designed for measuring personality traits rather than outcomes. This study
      provides a platform for designing a new PROM containing outcomes that matter to
      patients and can be influenced by primary care. Such a PROM would greatly enhance
      the value of primary care research.

PMID- 26297234
TI  - Susceptibility of bone marrow-derived macrophages to influenza virus infection is
      dependent on macrophage phenotype.
AB  - The role of the macrophage in influenza virus infection is complex. Macrophages
      are critical for resolution of influenza virus infections but implicated in
      morbidity and mortality in severe infections. They can be infected with influenza
      virus and consequently macrophage infection is likely to have an impact on the
      host immune response. Macrophages display a range of functional phenotypes, from
      the prototypical pro-inflammatory classically activated cell to alternatively
      activated anti-inflammatory macrophages involved in immune regulation and wound
      healing. We were interested in how macrophages of different phenotype respond to
      influenza virus infection and therefore studied the infection of bone marrow
      derived macrophages (BMDMs) of classical and alternative phenotype in vitro. Our
      results show that alternatively activated macrophages are more readily infected
      and killed by the virus than classically activated. Classically activated BMDMs
      express the pro-inflammatory markers inducible nitric oxide synthase (iNOS) and
      TNF-alpha, and TNF-alpha expression was further upregulated following infection.
      Alternatively activated macrophages express Arginase-1 and CD206; however,
      following infection, expression of these markers was downregulated whilst
      expression of iNOS and TNF-alpha was upregulated. Thus, infection can override
      the anti-inflammatory state of alternatively activated macrophages. Importantly,
      however, this results in lower levels of pro-inflammatory markers than those
      produced by classically activated cells. Our results showed that macrophage
      phenotype affects the inflammatory macrophage response following infection, and
      indicated that modulating the macrophage phenotype may provide a route to develop
      novel strategies to prevent and treat influenza virus infection. 

PMID- 26297236
TI  - Semliki Forest virus and Sindbis virus, but not vaccinia virus, require
      glycolysis for optimal replication.
AB  - Viruses are obligate intracellular pathogens which rely on the cell's machinery
      to produce the energy and macromolecules required for replication. Infection is
      associated with a modified metabolic profile and one pathway which can be
      modified is glycolysis. In this study, we investigated if the glycolysis pathway
      is required for alphavirus replication. Pre-treatment of Vero cells with three
      different glycolysis inhibitors (2-deoxyglucose, lonidamine and oxamate) resulted
      in a significant reduction (but not abrogation) of Semliki Forest virus and
      Sindbis virus replication, but not of the unrelated virus, vaccinia virus.
      Reduced virus yield was not associated with any significant cytotoxic effect and
      delayed treatment up to 3 h post-infection still resulted in a significant
      reduction. This suggested that glycolysis is required for optimal replication of
      alphaviruses by supporting post-entry life cycle steps. 

PMID- 26297235
TI  - Geodermatophilus sabuli sp. nov., a gamma-radiation-resistant actinobacterium
      isolated from desert limestone.
AB  - A novel gamma-radiation-resistant and Gram-staining-positive actinobacterium
      designated BMG 8133T was isolated from a limestone collected in the Sahara desert
      of Tunisia. The strain produced dry, pale-pink colonies with an optimum growth at
      35-40  degrees C and pH 6.5-8.0. Chemotaxonomic and molecular characteristics of
      the isolate matched those described for members of the genus Geodermatophilus.
      The peptidoglycan contained meso-diaminopimelic acid as diagnostic diamino acid.
      The main polar lipids were phosphatidylcholine, diphosphatidylglycerol,
      phosphatidylinositol, phosphatidylethanolamine and one unspecified glycolipid. MK
      9(H4) was the dominant menaquinone. Galactose and glucose were detected as
      diagnostic sugars. The major cellular fatty acids were branched-chain saturated
      acids iso-C16 : 0 and iso-C15 : 0. The DNA G+C content of the novel strain was
      74.5 %. The 16S rRNA gene sequence showed highest sequence identity with
      Geodermatophilus ruber (98.3 %). Based on phenotypic results and 16S rRNA gene
      sequence analysis, strain BMG 8133T is proposed to represent a novel species,
      Geodermatophilus sabuli sp. nov. The type strain is BMG 8133T ( = DSM 46844T =
      CECT 8820T).

PMID- 26297237
TI  - Development of a pharmacy practice intervention: lessons from the literature.
AB  - The development of health interventions is receiving increasing attention within
      the scientific literature. In the past, interventions were often based on the
      ISLAGIATT principle: that is, 'It seemed like a good idea at the time'. However,
      such interventions were frequently ineffective because they were either delivered
      in part or not at all, demonstrating a lack of fidelity, or because little
      attention had been paid to their development, content, and mode of delivery. This
      commentary seeks to highlight the latest methodological advances in the field of
      intervention development, drawing on health psychology literature, together with
      guidance from key organisations and research consortia which are setting
      standards for development and reporting. Those working within pharmacy practice
      research can learn from the more systematic approach being advocated, and apply
      these methods to help generate evidence to support new services and professional
      roles. 

PMID- 26297238
TI  - NSAIDs in paediatrics: caution with varicella!
AB  - Anti-inflammatory drugs have been suspected on several occasions to have promoted
      development of bacterial infection among varicella patients. Some countries have
      not implemented childhood varicella vaccination. Three cases in our hospital
      suggested the predisposing role of NSAIDs in varicella patient deterioration.
      Open access to these drugs widely increases their use and patient information
      should be continually provided in the medical offices and at dispensing pharmacy
      counters. Taking account of the benefit/risk balance and applying the simple
      precautionary principle, it would be appropriate to be cautious about the use of
      NSAIDs in the paediatric population. 

PMID- 26297239
TI  - Impact of an enhanced pharmacy discharge service on prescribing appropriateness
      criteria: a randomised controlled trial.
AB  - BACKGROUND: Older people are at increased risk of drug-related problems (DRPs)
      caused by inappropriate use or underuse of medications which may be increased
      during care transitions. OBJECTIVE: To examine the effects of applying a
      validated prescribing appropriateness criteria-set during medication review in a
      cohort of older (>=65 years) Australians at the time of discharge from hospital.
      SETTING: Private hospital and homes of older patients in Sydney, Australia.
      METHODS: Cognitively well English speaking patients aged 65 years or over taking
      five or more medications were recruited. A prescribing appropriateness criteria
      set and SF-36 health-related quality of life health (HRQoL) survey were applied
      to all patients at discharge. Patients were then randomly assigned to receive
      either usual care (control, n = 91) or discharge medication counselling and a
      medication review by a clinical pharmacist (intervention, n = 92). Medication
      review recommendations were sent to the general practitioners of intervention
      group patients. All patients were followed up at 3 months post discharge, where
      the prescribing appropriateness criteria-set was reapplied and HRQoL survey
      repeated. MAIN OUTCOME MEASURES change in the number of prescribing
      appropriateness criteria met; change in HRQoL; number and causes of DRPS
      identified by medication review; intervention patient medication recommendation
      implementation rates. RESULTS: There was no significant difference in the number
      of criteria applicable and met in intervention patients, compared to control
      patients, between follow-up and discharge (0.09 <= p <= 0.97). While the
      difference between groups was positive at follow-up for SF-36 scores, the only
      domain that reached statistical significance was that for vitality (p = 0.04).
      Eighty-eight intervention patient medication reviews identified 750 causes of
      DRPs (8.5 +/- 2.7 per patient). No causes of DRPs were identified in four
      patients. Of these causes, 76.4 % (573/750) were identified by application of the
      prescribing appropriateness criteria-set. GPs implemented a relatively low number
      (42.4 %, 318/750) of recommendations. CONCLUSION: Application of a prescribing
      appropriateness criteria-set during medication review in intervention patients
      did not increase the number of criteria met, nor result in a significant
      improvement in HRQoL. Higher recommendation implementation rates may require
      additional facilitators, including a higher quality of collaboration.

PMID- 26297240
TI  - CaMKII-dependent myofilament Ca2+ desensitization contributes to the frequency
      dependent acceleration of relaxation.
AB  - BACKGROUND: Previous studies suggest that CaMKII activity is required for
      frequency-dependent acceleration of relaxation (FDAR) in ventricular myocytes. We
      propose that the underlying mechanism involves CaMKII-dependent regulation of
      myofilament Ca(2+) sensitivity. METHODS AND RESULTS: Cardiac function was
      measured in mice using murine echo machine. [Ca(2+)]i and sarcomere length were
      measured by IonOptix Ca(2+) image system. Increasing pacing rate from 0.5 to 4 Hz
      in left ventricular myocytes induced frequency-dependent myofilament Ca(2+)
      desensitization (FDMCD) and FDAR. Acute inhibition of PKA or PKC had no effect,
      whereas CaMKII inhibition abolished both FDMCD and FDAR. Co-immunoprecipitation
      of CaMKII and troponin I (TnI) has been detected and CaMKII inhibition
      significantly reduced serine residue phosphorylation of TnI. Finally, chronic
      inhibition of CaMKII in vivo reduced TnI phosphorylation and abolished both FDAR
      and FDMCD, leading to impaired diastolic function. CONCLUSIONS: Our results
      suggest that CaMKII-dependent TnI phosphorylation is involved in FDMCD and the
      consequent FDAR and that CaMKII inhibition removes this mechanism and thus
      induces diastolic dysfunction.

PMID- 26297241
TI  - The prevalence of fecal incontinence and associated risk factors in older adults
      participating in the SABE study.
AB  - AIMS: To assess the prevalence of fecal incontinence (FI) and associated factors
      in older adults. METHODS: The prevalence and factors associated with FI in older
      adults were studied by means the SABE study (Health, Well-being, and Aging). A
      group of 1,345 subjects were interviewed during the third wave of the SABE study
      performed in Sao Paulo, in 2010. The study included 64.3% females; the mean age
      of the participants was 70.4 years. The dependent variable was the positive
      answer for the question "In the last 12 months, have you ever lost control of
      bowel movements or stools?". Descriptive analysis and hierarchical logistic
      regression were performed. The independent variables were as follows: (a)
      demographics: gender, age and (b) clinical characteristics: self-reported chronic
      diseases, presence of cognitive and/or functional decline, depression and urinary
      incontinence symptoms, and nutritional status. RESULTS: The overall prevalence of
      FI was 11,7%, being 8.3% and 13.2% for males and females respectively. Among male
      subjects, the presence of malnutrition was associated with FI and thus presented
      a high relative risk index for its occurrence. Among female subjects, age group
      70-74 years and some self-reported diseases or conditions such as mild
      depression, heart disease, urinary incontinence, and polypharmacy were associated
      with FI. For the first time in literature, polypharmacy appeared as an associated
      factor for FI for female older adults. CONCLUSIONS: The prevalence of FI in older
      adults was 11.7% and was mainly associated with advanced age and presence of
      heart disease, symptoms of depression, polypharmacy and urinary incontinence and
      malnutrition. Neurourol. Urodynam. 35:959-964, 2016. (c) 2015 Wiley Periodicals,
      Inc.

PMID- 26297242
TI  - Lipschutz ulcers: should we rethink this? An analysis of 33 cases.
AB  - OBJECTIVES: To describe the presentation and characteristics of patients with
      Lipschutz ulcers (LU) and to evaluate the role of a standard protocol in the
      aetiological diagnosis. STUDY DESIGN: Retrospective analysis of all cases of
      diagnosis of LU at our Vulvar Clinic during a five-year period. RESULTS: Of 110
      women with vulvar ulcers, 33 (30.0%) had a diagnosis of LU. The mean age was
      29.1+/-15.14 years (10-79 years). Nine (27.3%) were 35 years old or more. The
      majority had had their sexual debut (28, 84.8%). Ten patients (30.3%) referred
      had at least one previous similar episode. Twenty-five (75.7%) had non
      gynecological symptoms in the week before. The ulcers were located most
      frequently on the vestibule (19, 57.6%) and the labia minora (10, 30.3%).
      Isolated lesions on the left side were uncommon (3, 9.1%). Most had multiple (22,
      66.7%) lesions. The mean time to full healing of the lesions was 15.6+/-6.20
      days. A microbiological possible cause was identified in 9 (27.3%) patients: CMV
      (3 cases), Mycoplasma pneumoniae (3 cases), EBV (2 cases) and PVB19 (1 case). The
      protocol did not include systematic biopsies, blood count differentials, C
      reactive protein and liver enzymes, which may have lead to some missed diagnosis.
      CONCLUSIONS: LU can be found in women of any age, most of them sexually active.
      In most cases the lesions are preceded by non-gynecological symptoms and
      recurrence is common. Most lesions occur on the vestibule and labia minora, being
      rarely found isolated on the left side. Viruses seem to be the most frequent
      associated agents but Mycoplasma pneumoniae serology should be considered. In one
      case there was a possible role for PVB19. A standard protocol can effectively
      exclude sexually transmitted diseases and lead to a diagnosis in up to a third of
      cases.

PMID- 26297243
TI  - Postmortem computed tomography findings in the thorax - Experimental evaluation.
AB  - OBJECTIVE: Experimental fatal models were prepared to investigate the time
      related course of lung changes using postmortem CT (PMCT). This study was
      approved by our institutional animal ethics committee. MATERIALS AND METHODS:
      Twenty-four NZW rabbits (female 24, 2.30-4.30 (mean 3.10)kg) were divided into 4
      fatal groups; drowning, hypothermia, bag suffocation, and Potassium Chloride
      intravenous (control) group. All individuals were examined by CT (Aquilion CX,
      Toshiba, Japan) on postmortem time course until detection of putrefaction air.
      The percent of aerated lung volume (%ALV=100*(ALV/total lung volume)) was
      measured and the pleural space fluid was investigated by axial imaging. A paired
      t-test and Bonferroni/Dunn study were employed for statistical evaluation.
      RESULTS: In intra-group analysis, the %ALV showed statistically different periods
      compared with each pre-image: 4-48 h in control, 1-24h in drowning, 5-6h in
      hypothermia, and 1-4h in bag suffocation. In inter-group comparison (compared
      with control group), the %ALV increased in suffocation and decreased in drowning
      within 12h. The %ALV remained significantly high in hypothermia until 24h. The
      earliest detection times of pleural space fluid collection were different in each
      group: control (20 h), drowning (18 h), suffocation (36 h), and hypothermia (95
      h). CONCLUSION: The lung hypostasis and the appearance of pleural space fluid
      collection presented differently in individual causes of death and depending on
      the postmortem time.

PMID- 26297244
TI  - Schmallenberg virus: experimental infection in goats and bucks.
AB  - BACKGROUND: Schmallenberg virus (SBV) is an emerging Orthobunyavirus of ruminant
      livestock species currently circulating in Europe. SBV causes a subclinical or
      mild disease in adult animals but vertical transmission to pregnant dams may lead
      to severe malformations in the offspring. Data on the onset of clinical signs,
      viremia and seroconversion in experimentally infected adult animals are available
      for cattle and sheep but are still lacking for goats. For a better understanding
      of the pathogenesis of SBV infection in adult ruminants, we carried out
      experimental infections in adult goats. Our specific objectives were: (i) to
      record clinical signs, viremia and seroconversion; (ii) to monitor viral
      excretion in the semen of infected bucks; (iii) to determine in which tissues SBV
      replication took place and virus-induced lesions developed. RESULTS: Four goats
      and two bucks were inoculated with SBV. Virus inoculation was followed by a short
      viremic phase lasting 3 to 4 days and a seroconversion occurring between days 7
      and 14 pi in all animals. The inoculated goats did not display any clinical
      signs, gross lesions or histological lesions. Viral genomic RNA was found in one
      ovary but could not be detected in other organs. SBV RNA was not found in the
      semen samples collected from two inoculated bucks. CONCLUSIONS: In the four goats
      and two bucks, the kinetics of viremia and seroconversion appeared similar to
      those previously described for sheep and cattle. Our limited set of data provides
      no evidence of viral excretion in buck semen.

PMID- 26297245
TI  - Peritoneal vaginoplasty by Luohu I and Luohu II technique: a comparative study of
      the outcomes.
AB  - BACKGROUND: Surgical vaginoplasty is the standard treatment for women suffering
      from Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. This study compares the
      advantages and disadvantages of Luohu I technique or its modification, Luohu II
      technique. METHODS: Women with MRKH syndrome undergoing laparoscopic peritoneal
      vaginoplasty using either the Luohu I (N = 145) or Luohu II (N = 155) technique
      were recruited. We compare the effectiveness of the Luohu II and one of Luohu I.
      Sexual satisfaction was checked by Female Sexual Function Index. RESULTS: There
      was no significant difference in the mean operation time, volume of
      intraoperative blood loss, time for the first passage of gas, sexual satisfaction
      (and hospital stay for patients in either group (P > 0.05). But patients in the
      Luohu II group had a significantly lower incidence of complications than patients
      in the Luohu I group. All patients had vaginal depths more than 9 cm over 3
      months post-surgery. CONCLUSIONS: Compared with the traditional Luohu I
      laparoscopic peritoneal vaginoplasty, the Luohu II operation is easier to perform
      and causes less damage to the bladder and rectum. The physiological and
      anatomical features of the artificial vagina resemble the normal vagina in both
      techniques.

PMID- 26297246
TI  - Effects of antibiotics on biofilm and unattached cells of a clinical
      Staphylococcus aureus isolate from bone and joint infection.
AB  - Treatment of orthopaedic infections remains challenging owing to the inability of
      antibiotics to eradicate biofilms and prevent their regrowth. The present study
      characterized the effects of 12 antibiotics on in vitro biofilm formed by a
      representative strain of meticillin-susceptible Staphylococcus aureus (MSSA)
      isolated from a bone infection. Determination of the minimum biofilm eradication
      concentrations indicated that in vitro eradication of 24 h-old biofilms required
      concentrations up to 51,200 times higher than MICs. The influence of the same
      panel of antibiotics was also investigated on biofilm formation at concentrations
      including the breakpoints, by numbering viable cells in the suspensions
      (individual cells) and the biofilm biomass. Except for fusidic acid, the presence
      of antibiotics during the initial steps of biofilm formation resulted in
      significant decreases in the number of sessile viable bacteria at the highest
      concentrations tested. Ceftarolin, daptomycin, fosfomycin, gentamicin, ofloxacin,
      rifampicin and vancomycin were the most effective drugs. Confocal microscopy
      analysis indicated that daptomycin was more efficient at bacteria lysis than
      gentamicin and vancomycin. However, viable individual cells were still detectable
      in the assays performed with ceftarolin, fosfomycin, ofloxacin, rifampicin and
      vancomycin at concentrations for which no sessile cells were detected. Although
      none of the molecules tested was effective at classical therapeutic
      concentrations against 24 h-old MSSA biofilms, all except fusidic acid were able
      to impair biofilm formation at concentrations near the breakpoints. However,
      presence of viable individual unattached cells could imply a significant risk of
      microbial dissemination and increased risk of infections.

PMID- 26297247
TI  - Hanseniaspora jakobsenii sp. nov., a yeast isolated from Bandji, a traditional
      palm wine of Borassus akeassii.
AB  - Investigation of the microbial diversity of Bandji, a traditional palm wine from
      Burkina Faso (West Africa) revealed the presence of two yeast isolates (YAV16 and
      YAV17T) with unusual phenotypic and genotypic characteristics. The isolates
      divide by bipolar budding with no production of ascospores. Phylogenetic analysis
      of concatenated sequences of the 26S rRNA gene D1/D2 and internal transcribed
      spacer (ITS) regions indicated that the novel species was most closely related to
      Kloeckera lindneri and Hanseniaspora valbyensis. The new isolates differed from
      K. lindneri NRRL Y-17531T and H. valbyensis CBS 479T by substitutions in the
      D1/D2 region of 12 and 16 nt respectively. The divergence in the ITS region from
      the closely related species was characterized by substitutions of 45-46 nt.
      Repetitive palindromic PCR (rep-PCR) profiles of YAV16 and YAV17T were also
      significantly different from those of K. lindneri MUCL 31146T ( = NRRL Y-17531T),
      H. valbyensis NCYC 17T ( = CBS 479T) and other species of the genus
      Hanseniaspora. Based on the results of the phenotypic and genotypic
      characterizations, it was concluded that the new isolates represent a novel
      species for which the name Hanseniaspora jakobsenii sp. nov. is proposed with
      YAV17T ( = CBS 12942T = DSM 26339T = NCYC 3828T; MycoBank number MB 805785) as
      the type strain. 

PMID- 26297248
TI  - Depletion of NADP(H) due to CD38 activation triggers endothelial dysfunction in
      the postischemic heart.
AB  - In the postischemic heart, coronary vasodilation is impaired due to loss of
      endothelial nitric oxide synthase (eNOS) function. Although the eNOS cofactor
      tetrahydrobiopterin (BH4) is depleted, its repletion only partially restores eNOS
      mediated coronary vasodilation, indicating that other critical factors trigger
      endothelial dysfunction. Therefore, studies were performed to characterize the
      unidentified factor(s) that trigger endothelial dysfunction in the postischemic
      heart. We observed that depletion of the eNOS substrate NADPH occurs in the
      postischemic heart with near total depletion from the endothelium, triggering
      impaired eNOS function and limiting BH4 rescue through NADPH-dependent salvage
      pathways. In isolated rat hearts subjected to 30 min of ischemia and reperfusion
      (I/R), depletion of the NADP(H) pool occurred and was most marked in the
      endothelium, with >85% depletion. Repletion of NADPH after I/R increased NOS
      dependent coronary flow well above that with BH4 alone. With combined NADPH and
      BH4 repletion, full restoration of NOS-dependent coronary flow occurred. Profound
      endothelial NADPH depletion was identified to be due to marked activation of the
      NAD(P)ase-activity of CD38 and could be prevented by inhibition or specific
      knockdown of this protein. Depletion of the NADPH precursor, NADP(+), coincided
      with formation of 2'-phospho-ADP ribose, a CD38-derived signaling molecule.
      Inhibition of CD38 prevented NADP(H) depletion and preserved endothelium
      dependent relaxation and NO generation with increased recovery of contractile
      function and decreased infarction in the postischemic heart. Thus, CD38
      activation is an important cause of postischemic endothelial dysfunction and
      presents a novel therapeutic target for prevention of this dysfunction in
      unstable coronary syndromes. 

PMID- 26297249
TI  - Protein folding guides disulfide bond formation.
AB  - The Anfinsen principle that the protein sequence uniquely determines its
      structure is based on experiments on oxidative refolding of a protein with
      disulfide bonds. The problem of how protein folding drives disulfide bond
      formation is poorly understood. Here, we have solved this long-standing problem
      by creating a general method for implementing the chemistry of disulfide bond
      formation and rupture in coarse-grained molecular simulations. As a case study,
      we investigate the oxidative folding of bovine pancreatic trypsin inhibitor
      (BPTI). After confirming the experimental findings that the multiple routes to
      the folded state contain a network of states dominated by native disulfides, we
      show that the entropically unfavorable native single disulfide [14-38] between
      Cys14 and Cys38 forms only after polypeptide chain collapse and complete
      structuring of the central core of the protein containing an antiparallel beta
      sheet. Subsequent assembly, resulting in native two-disulfide bonds and the
      folded state, involves substantial unfolding of the protein and transient
      population of nonnative structures. The rate of [14-38] formation increases as
      the beta-sheet stability increases. The flux to the native state, through a
      network of kinetically connected native-like intermediates, changes dramatically
      by altering the redox conditions. Disulfide bond formation between Cys residues
      not present in the native state are relevant only on the time scale of collapse
      of BPTI. The finding that formation of specific collapsed native-like structures
      guides efficient folding is applicable to a broad class of single-domain
      proteins, including enzyme-catalyzed disulfide proteins. 

PMID- 26297250
TI  - Papillary renal cell carcinoma: correlation of tumor grade and histologic
      characteristics with clinical outcome.
AB  - Histologic prognostic parameters in papillary renal cell carcinoma (PRCC) are
      unclear. The aims were to review the clinicopathological features of PRCC,
      including Fuhrman grade and International Society of Urological Pathology (ISUP)
      nucleolar grade, and to identify parameters that may be independent prognostic
      indicators. PRCCs in patients treated by nephrectomy were retrieved from the
      pathology files from 1984 to 2010. Parameters studied included tumor
      multifocality, size, PRCC type (1 or 2), Fuhrman grade, ISUP nucleolar grade,
      presence of necrosis, lymphovascular invasion, and stage at presentation. Cancer
      specific survival (CSS) and overall survival (OS) were used as prognostic
      measures. Of 154 PRCCs, 112 (73%) were type 1, and 42 (27%), type 2. A total of
      125 patients were male, and 29, female, with ages from 26 to 86 (mean, 62.7)
      years. Fuhrman grade was 1 in 8 (5%), 2 in 95 (62%), 3 in 49 (32%), and 4 in 2
      (1%) tumors, respectively. ISUP nucleolar grade was 1 in 47 (31%), 2 in 56 (36%),
      3 in 49 (32%), and 4 in 2 (1%) tumors, respectively. Mean follow-up interval was
      73.9 months (0.13-222 months). ISUP nucleolar grade was a significant predictor
      of both CSS and OS in univariate (CSS, P = .001; OS, P = .004) and multivariate
      (CSS, P = .04; OS, P = .008) analyses, whereas Fuhrman grade was only predictive
      of CSS in univariate (P = .001) and multivariate (P = .04) analyses. Only ISUP
      nucleolar grade and lymphovascular invasion were independently prognostic for CSS
      and OS in univariate and multivariate analyses. Therefore, the ISUP nucleolar
      grade appears to be superior in predicting survival in patients with PRCC. 

PMID- 26297251
TI  - The H3.3 K27M mutation results in a poorer prognosis in brainstem gliomas than
      thalamic gliomas in adults.
AB  - Brainstem and thalamic gliomas are rare, and they are poorly understood in
      adults. Genetic aberrations that occur in these tumors are still unknown. In this
      study, we investigated whether thalamic gliomas have different genetic
      aberrations and clinical outcomes compared with brainstem gliomas in adults.
      Forty-three glioma samples were selected, including 28 brainstem and 15 thalamic
      gliomas. The frequency of the K27M mutation in adult midline gliomas was 58.1%.
      High-grade gliomas in the thalamus were statistically significantly more numerous
      than brainstem gliomas. Patients with K27M mutant brainstem gliomas had a
      significantly shorter overall survival than patients with wild-type tumors (P =
      .020) by Cox regression after adjustment for other independent risk factors.
      However, there was no statistical tendency toward a poorer overall survival in
      thalamic gliomas containing the K27M mutation compared with wild-type tumors. The
      presence of the K27M mutation significantly corresponded with mutations in TP53
      in thalamic gliomas. Interestingly, the K27M mutation was mutually exclusive with
      mutations in IDH1, which was detected only in brainstem gliomas. The microarray
      data identified 86 differentially expressed genes between brainstem and thalamic
      gliomas with the K27M mutation. The cyclin-dependent kinase 6 (CDK6) gene, which
      plays an important role in cancer pathways, was found to be differentially
      expressed between brainstem and thalamic gliomas with K27M mutations. Although
      the K27M mutation was frequently observed in adult brainstem and thalamic
      gliomas, this mutation tended to be associated with a poorer prognosis in
      brainstem gliomas but not in thalamic gliomas. Brainstem gliomas may present
      different genetic aberrations from thalamic gliomas. These differences may
      provide guidance for therapeutic decisions for the treatment of adult brainstem
      and thalamic gliomas, which may have different molecular targets. 

PMID- 26297252
TI  - Immunohistochemical characterization of the regenerative compartment in biliary
      atresia: a comparison between Kasai procedure and transplant cases.
AB  - Biliary atresia (BA) accounts for most cases of pathologic infantile jaundice,
      which may lead to cirrhosis and eventually necessitate liver transplantation
      (LT). A cardinal histologic feature of BA is ductular reaction (DR), reflecting
      activation of the regenerative compartment in liver. We examined the
      immunohistochemical attributes of the progenitor cell population and its
      immediate descendants in BA patients undergoing Kasai procedure (KP) or LT. The
      BA cases were divided into those undergoing KP (n = 24) and those undergoing LT
      (n = 64). Immunohistochemistry for CD56, CK7, and CK19 was performed. Patients
      with BA (both KP and LT groups) had more DR than controls (scores 2.4, 2.2, and
      0.1, respectively; P < .001), but the degree of DR did not differ between BA
      patients undergoing KP compared to LT. There was significantly more CD56 staining
      in DR in LT (2.5) versus KP samples (1.3; P < .001), with a trend toward the same
      pattern in hepatocyte progenitor cells in these samples (0.6 versus 0.2; P =
      .05). In intermediate hepatocytes, CK7 staining was higher in LT versus KP
      samples (1.7 versus 0.3; P < .001). No differences in CK19 staining were noted in
      the cell types in different BA groups. Immunohistochemistry suggests that the
      regenerative compartment is expanded in patients undergoing LT for BA, compared
      to patients with an earlier stage of disease undergoing KP. These observations
      support the notion that there is more active regeneration in livers with advanced
      stage BA and highlight the immunophenotypic heterogeneity of progenitor cells in
      different phases of the disease. 

PMID- 26297253
TI  - Down-regulation of cytoplasmic PLZF correlates with high tumor grade and tumor
      aggression in non-small cell lung carcinoma.
AB  - There are currently no effective prognostic biomarkers for lung cancer.
      Promyelocytic leukemia zinc finger (PLZF), a transcriptional repressor, has a
      role in cell cycle progression and tumorigenicity in various cancers. The
      expression and value of PLZF in lung carcinoma, particularly in the subclass of
      non-small cell lung carcinoma (NSCLC), has not been studied. Our aim was to study
      the immunohistochemical expression of PLZF in lung adenocarcinoma and squamous
      cell carcinoma and correlate the alteration of PLZF expression with tumor
      differentiation, lymph node metastasis, tumor stage, and overall survival. A
      total of 296 NSCLCs being mounted on tissue microarray (181 adenocarcinomas and
      91 squamous cell carcinomas) were investigated. Moderate to strong expression of
      PLZF was found in the cytoplasm of all the nonneoplastic respiratory epithelium
      and most (89.9%) well-differentiated adenocarcinoma. The proportions of
      moderately differentiated, poorly differentiated adenocarcinoma, and paired lymph
      node adenocarcinoma metastases that demonstrated negative or only weak PLZF
      reactivity were 75.6%, 97.2%, and 89.9%, respectively. The expression of PLZF in
      squamous cell carcinoma was mostly weak or absent and significantly lower than
      that in adenocarcinoma of the same grade (P < .0005). The loss of cytoplasmic
      PLZF strongly correlated with high tumor grade and lymph node metastasis in both
      squamous carcinoma and adenocarcinoma (P < .0001). Down-regulation of PLZF also
      correlated with higher tumor stage and shorter overall survival (P < .05). These
      results support a prognostic value for loss of cytoplasmic PLZF expression in the
      stratification of NSCLC and a possible role of cytoplasmic shift and down
      regulation of PLZF in the pathogenesis of NSCLC. 

PMID- 26297254
TI  - Dual NRASQ61R and BRAFV600E mutation-specific immunohistochemistry completes
      molecular screening in melanoma samples in a routine practice.
AB  - NRAS and BRAF mutational status has become mandatory to treat patients with
      metastatic melanomas. Mutation-specific immunohistochemistry (IHC) can help
      analyze challenging tumor samples. We report our experience integrating NRASQ61R
      (SP174) and BRAFV600E (VE1) IHC in routine practice in a cancer molecular genetic
      platform. All samples screened for BRAF and NRAS mutations during the year 2014
      were analyzed by IHC and pyrosequencing, with an independent analysis of the 2
      methods. Cases with first-line discordant results benefited from a complementary
      second-round IHC and next-generation sequencing (NGS) with a final interpretation
      taking into account the results of pyrosequencing, IHC, NGS, and quantification
      of the tumor cells. We analyzed 111 consecutive formalin-fixed and paraffin
      embedded melanoma samples from 101 patients. Twenty-two and 11 samples were
      concordant for BRAFV600E and NRASQ61R mutations, respectively. Second-round
      analyses of 9 discordant and 1 molecularly inconclusive samples allowed
      conclusion in 4 further mutated samples (2 BRAFV600E and 2 NRASQ61R). A sample
      remained NRASQ61R IHC negative but NRASQ61R mutated with molecular methods.
      Overall, BRAFV600 and NRASQ61 mutation frequencies were 31.7% and 30.7%,
      respectively. When compared to molecular results, the sensitivity and specificity
      of IHC were 100% for BRAFV600E IHC and 92.3% and 98.9% for NRASQ61R IHC,
      respectively. IHC interpretation required a more stringent cutoff for BRAFV600E
      IHC than NRASQ61R to minimize false results. We conclude that NRASQ61R and
      BRAFV600E IHC coupled with NGS allow detection of mutations in melanoma
      challenging samples. 

PMID- 26297255
TI  - Frequent frameshift mutations in 2 mononucleotide repeats of RNF43 gene and its
      regional heterogeneity in gastric and colorectal cancers.
AB  - RNF43, an E3 ligase, inhibits Wnt signaling by removing Wnt receptors and behaves
      as a candidate tumor suppressor. Recent studies identified that RNF43 gene was
      frequently mutated in gastric (GC), colorectal (CRC), and endometrial cancers
      with high microsatellite instability (MSI-H). The aim of this study is to explore
      whether RNF43 gene is mutated in GC and CRC in Korean patients and whether the
      mutations show regional intratumoral heterogeneity (ITH). We analyzed 2 exonic
      repeats (C6 and G7) of RNF43 in 78 GCs and 130 CRCs by single-strand conformation
      polymorphism and DNA sequencing analyses. Also, we analyzed regional ITH of RNF43
      mutation in 16 CRCs. We found RNF43 frameshift mutation in MSI-H (50/118), the
      incidence of which was significantly higher than that in microsatellite
      stable/low microsatellite instability (1/90). GCs showed a significantly higher
      incidence of the mutation than CRCs (66.7% of GC and 32.9% of CRC with MSI-H).
      Also, we found that all of the 7 CRCs with the mutations harbored mutational ITH.
      By immunohistochemistry, we observed that loss of RNF43 expression was
      significantly more common in those with RNF43 frameshift mutation than those with
      wild-type RNF43. Our data indicate that RNF43 gene harbored not only exceedingly
      high mutations but also mutational ITH, which together might play a role in
      tumorigenesis of GC and CRC. We suggest that regional analysis is required for a
      more comprehensive evaluation of the mutation status in these tumors. 

PMID- 26297256
TI  - Clinical, pathologic, and outcome study of hyperplastic and sessile serrated
      polyps in inflammatory bowel disease.
AB  - There is evidence that some cancers in patients with inflammatory bowel disease
      (IBD) develop via the serrated pathway of carcinogenesis. This study examined the
      clinicopathological features and outcome of 115 IBD patients (65 with ulcerative
      colitis, 50 with Crohn disease), all with at least 1 serrated polyp at endoscopy
      or colon resection, including the presence of synchronous and metachronous
      conventional neoplastic lesions (dysplasia or adenocarcinoma), over an average
      follow-up period of 56.4 months. Conventional neoplasia was categorized as flat
      dysplasia (low or high grade), sporadic adenoma, adenoma-like dysplasia
      associated lesion or mass, or adenocarcinoma. Overall, 97% of patients had at
      least 1 hyperplastic polyp (HP), 6% had a sessile serrated adenoma/polyp, and
      none had a traditional serrated adenoma. Eight patients (7%) had a synchronous
      conventional neoplastic lesion; only 1 had flat dysplasia (1%) and 2 had
      adenocarcinoma (2%). Thirteen patients developed a metachronous conventional
      neoplastic lesion, with 8 developing their conventional neoplasm within an area
      of previous or concurrent colitis; only 1 patient developed flat dysplasia (1%),
      and none developed adenocarcinoma. A higher proportion of patients with both an
      HP and a synchronous conventional neoplastic lesion at index developed a
      metachronous conventional neoplastic lesion, compared with those with an index HP
      only (25% versus 7%). These results suggest that IBD patients (both ulcerative
      colitis and Crohn disease patients) with HP have a very low risk of developing a
      conventional neoplastic lesion (flat dysplasia or adenocarcinoma) that would
      warrant surgical resection. 

PMID- 26297257
TI  - Strong immunoexpression of midkine is associated with multiple lymph node
      metastases in BRAFV600E papillary thyroid carcinoma.
AB  - Midkine is a multifunctional, heparin-binding growth factor that is frequently
      expressed in patients with malignancies but is undetectable in healthy adults. In
      various cancers, high expression of midkine is associated with aggressive
      clinical behavior and a poor prognosis. In the present study, we investigated the
      expression of midkine in papillary thyroid carcinoma (PTC) and assessed its
      association with a BRAFV600E mutation and the clinicopathological parameters. We
      determined the presence of a BRAFV600E mutation in 79 cases of PTC and examined
      the effects of the BRAFV600E mutation on midkine expression in primary
      thyrocytes. In addition, we evaluated the association between midkine expression
      and various clinicopathological parameters. We found that midkine is more
      frequently expressed in BRAFV600E PTC (68.3%) than in BRAF wild-type PTC (18.8%).
      BRAFV600E transduction could up-regulate midkine expression in primary
      thyrocytes. Moreover, midkine expression was associated with multiple lymph node
      (>=5) metastases in BRAFV600E PTC. In conclusion, our results suggest that
      midkine expression could be a clinically useful marker in predicting the presence
      of multiple lymph node metastases in BRAFV600E PTC. 

PMID- 26297258
TI  - Complex autoregulation of the post-transcriptional regulator RsmA in Pseudomonas
      aeruginosa.
AB  - RsmA is a post-transcriptional RNA-binding protein that acts as a pleiotropic
      global regulator of mRNAs in the opportunistic pathogen Pseudomonas aeruginosa.
      Upon binding to its target, RsmA impedes the translation of the mRNA by the
      ribosome. The RsmA regulon affects over 500 genes, many of which have been
      identified as important in the pathogenicity of P. aeruginosa. Whilst the
      regulatory function of RsmA is relatively well characterized, the genetic
      regulation of rsmA itself at the transcriptional and translational levels remains
      poorly understood. Here, we show that RsmA is capable of self-regulation through
      an unorthodox mechanism. This regulation occurs via direct interaction of the
      protein with an RsmA-binding site located in the early portion of its coding
      sequence. To the best of our knowledge this is the first report of such an
      unusual regulation in pseudomonads. 

PMID- 26297261
TI  - Relapsed Acute Myeloid Leukemia: Need for Innovative Treatment Strategies to
      Improve Outcome.
AB  - Relapse continues to be a major hurdle in achieving cure in patients with acute
      myeloid leukemia (AML). The outcome after relapse is not uniform in all patients
      with AML and is dependent on several prognostic variables, including age,
      cytogenetics at initial diagnosis, duration of first complete remission, whether
      an allogeneic stem cell transplant was performed during first complete remission,
      and the presence of a number of molecular aberrations. Despite extensive research
      over the past several decades, there is no standard of care for treating patients
      with relapsed AML. This is possibly due to the accrual of patients with widely
      different disease profiles in most trials for relapsed AML. With increasing
      insights into the disease biology based on identification of pathogenic and
      aberrant molecular and cellular pathways, novel therapeutic strategies are
      emerging. Hopefully in the near future, we can improve the outcome of patients
      with relapsed AML with treatment strategies based on identification of specific
      targets and methods to overcome these aberrant processes. 

PMID- 26297259
TI  - A mathematical model of the dynamics of prion aggregates with chaperone-mediated
      fragmentation.
AB  - Prions are proteins most commonly associated with fatal neurodegenerative
      diseases in mammals but are also responsible for a number of harmless heritable
      phenotypes in yeast. These states arise when a misfolded form of a protein
      appears and, rather than be removed by cellular quality control mechanisms,
      persists. The misfolded prion protein forms aggregates and is capable of
      converting normally folded protein to the misfolded state through direct
      interaction between the two forms. The dominant mathematical model for prion
      aggregate dynamics has been the nucleated polymerization model (NPM) which
      considers the dynamics of only the normal protein and the aggregates. However,
      for yeast prions the molecular chaperone Hsp104 is essential for prion
      propagation. Further, although mammals do not express Hsp104, experimental assays
      have shown Hsp104 also interacts with mammalian prion aggregates. In this study,
      we generalize the NPM to account for molecular chaperones and develop what we
      call the enzyme-limited nucleated polymerization model (ELNPM). We discuss
      existence, uniqueness and stability of solutions to our model and demonstrate
      that the NPM represents a quasi-steady-state reduction of our model. We validate
      the ELNPM by demonstrating agreement with experimental results on the yeast prion
      PSI(+) that could not be supported by the NPM. Finally, we demonstrate that, in
      contrast to the NPM, the ELNPM permits the coexistence of multiple prion strains.

PMID- 26297262
TI  - Prognosis and Molecular Monitoring in Chronic Myeloid Leukemia.
AB  - Tyrosine kinase inhibitors with activity against BCR-ABL form the cornerstone of
      CML therapy, and are particularly effective in those with chronic-phase disease.
      Because some patients exhibit primary resistance or secondary failure to TKI
      therapy, it is recommended that continued monitoring of disease burden be
      performed. In this article, we review methods of detecting the Philadelphia
      chromosome and BCR-ABL transcript, and discuss the correlation of response with
      patient outcomes. Expert guidelines that incorporate definitions and milestones
      of response are referenced to aid in clinical decision-making.

PMID- 26297263
TI  - Factors Affecting Early Molecular Response in Chronic Myeloid Leukemia.
AB  - OBJECTIVES: There is controversy about whether 3- or 6-month molecular assessment
      predicts progression-free and overall survival in those with chronic myeloid
      leukemia (CML). The factors predicting molecular response at 3, 6, and 12 months
      have not been studied extensively. The study objective was to study the factors
      affecting molecular response at 3 and 6 months in patients with CML who are
      receiving imatinib mesylate. METHODS: We prospectively enrolled patients with
      newly diagnosed CML who were receiving imatinib mesylate as the initial therapy
      for CML. The diagnosis of CML was based on clinical examination, bone marrow, and
      demonstration of BCR ABL(IS) transcripts by polymerase chain reaction. The
      molecular response(IS) was assessed at 3, 6, and 12 months by GeneXpert (Cepheid,
      Sunnyvale, CA) and co-related with various baseline characteristics of patients.
      We also looked at whether early achievement of a complete hematologic response
      within 6 weeks predicts molecular response at 3 or 6 months. The study took place
      at a tertiary care hospital in Northwest India catering to patients belonging to
      low-middle socioeconomic status. RESULTS: We enrolled 131 patients with CML in
      the chronic phase from July 1, 2013, to August 31, 2014. The median age of the
      patients was 40 years (range, 13-67) with a male preponderance (61% were male).
      Most patients presented with symptoms of low-grade fever (52.7%) and abdominal
      fullness (26.7%). Spleen was palpable in 84.7% of patients. The median hemoglobin
      at presentation was 10.8 g/dL (range, 4.8-18.4 g/dL), white cell count was 138.3
      * 10(9)/L (4.1-697 * 10(9)/L), and platelet count was 326 * 10(9)/L (85-1819 *
      10(9)/L). The median number of peripheral blood basophils was 3% (range, 0%-20%),
      and blasts were 3% (range, 0%-10%). Myelofibrosis of more than grade 1 was
      present in 30% of patients. Most patients belonged to intermediate Sokal (45.8%)
      and Hasford (55%) scores and low EUropean Treatment Outcome Study (78.6%) score.
      Of 128 evaluable patients at 3 months, 96.9% achieved complete hematologic
      remission (CHR) and 82.3% achieved BCR ABL(IS) of less than 10%. None of the
      patients who had BCR ABL(IS) > 10% at 3 months achieved BCR ABL(IS) < 1% at 6
      months or < 0.1% at 12 months. Early achievement of CHR (< 6 weeks), peripheral
      blood blast count of < 5%, and lactate dehydrogenase < 851 U/L were significantly
      associated with achievement of BCR ABL(IS) < 10% at 3 months and BCR ABL(IS) < 1%
      at 6 months. CONCLUSIONS: We found that BCR ABL(IS) assessment at 3 months is
      superior to assessment at 6 months. Patients with CML in the chronic phase who
      achieve CHR within 6 weeks are more likely to achieve BCR ABL(IS) < 10% at 3
      months and < 1% at 6 months than patients who achieve CHR between 7 and 12 weeks.

PMID- 26297264
TI  - Mutations in the BCR-ABL1 Kinase Domain and Elsewhere in Chronic Myeloid
      Leukemia.
AB  - Chronic myeloid leukemia (CML) has been the first human malignancy to be
      associated, more than 50 years ago, with a consistent chromosomal abnormality-
      the t(9;22)(q34;q11) chromosomal translocation. The resulting BCR-ABL1 fusion
      gene, encoding a tyrosine kinase with deregulated activity, has a central role in
      the pathogenesis of CML. Ancestral or additional genetic events necessary for CML
      to develop have long been hypothesized but never really demonstrated. CML can
      successfully be treated with tyrosine kinase inhibitors (TKIs). Mutations in the
      BCR-ABL1 kinase domain might arise, however, that confer resistance to 1 or more
      of the currently available TKIs. Hence, the critical role of BCR-ABL1 mutation
      screening for optimal therapeutic management, with the current gold standard
      technique, conventional sequencing, likely to be replaced soon by ultra-deep
      sequencing. Mutations in genes other than BCR-ABL1 include ASXL1, TET2, RUNX1,
      DNMT3A, EZH2, and TP53 in chronic phase patients and RUNX1, ASXL1, IKZF1, WT1,
      TET2, NPM1, IDH1, IDH2, NRAS, KRAS, CBL, TP53, CDKN2A, RB1, and GATA-2 mutations
      in advanced phase patients. The latter also display additional cytogenetic
      abnormalities, including submicroscopic regions of gain or loss that only single
      nucleotide polymorphism arrays or array comparative genomic hybridization can
      detect. Whether whole genome/exome sequencing studies will uncover novel
      mutations relevant for pathogenesis, progression, and risk-adapted therapy is
      still unclear.

PMID- 26297265
TI  - Retrospective Study of Allogeneic Hematopoietic Stem Cell Transplantation in
      Philadelphia Chromosome-Positive Leukemia: 25 Years' Experience at Gustave Roussy
      Cancer Campus.
AB  - The introduction of tyrosine kinase inhibitor (TKI) therapy has markedly reduced
      the use of allogeneic (allo) hematopoietic stem cell transplantation (HSCT),
      which is no longer standard practice in the first chronic phase in chronic
      myelogenous leukemia and is currently reserved after failure of TKI or in
      advanced phase of disease. We compared the outcome of Philadelphia chromosome
      positive (Ph+) leukemia patients who received a first allo-HSCT in our center in
      both the pre-TKI era and the TKI era. The primary end point was to compare the 2
      groups' overall survival (OS), leukemia-free survival (LFS), cumulative incidence
      of nonrelapse mortality, and relapse incidence. The secondary end point was to
      underline in the TKI era the impact of the pretransplantation minimal residual
      disease (MRD) on the outcomes. A total of 69 patients with Ph+ leukemia were
      included and their outcomes analyzed. For the purpose of this analysis, we
      defined 2 groups: group A (n = 39) included patients treated in the pre-TKI era,
      treated from January 1989 until December 2001, and group B (n = 30) included
      patients treated in the TKI era, treated from January 2002 until December 2013.
      Additional analysis was performed in group B for whom detailed TKIs and MRD data
      were collected. The study took place in our cancer center in the department of
      HSCT, Villejuif, France. The median follow-up duration for group A was 116.1
      months (range, 1.1 to 240.1 months) and for group B was 8.3 months (range, 3.5 to
      141.7 months). At 3 years, the LFS and OS were higher in group B (respectively,
      66% and 71%) than in group A (respectively, 63% and 57%) (P > .05). The LFS and
      OS at 3 years of the pretransplantation MRD-negative (< 0.01%) patients were
      significantly (P < .05) higher (respectively, 83% and 94%) than the
      pretransplantation MRD-positive patients (respectively, 43% and 46%). Our data,
      although statistically not significant, suggest better outcomes for Ph+ leukemia
      patients undergoing allo-HSCT in the TKI era. Mostly TKI does not adversely
      affect the transplantation outcomes and can be used successfully as a bridge to
      allo-HSCT, especially in advanced disease. In addition, we highlight the
      importance of obtaining deep pretransplantation MRD negativity.

PMID- 26297266
TI  - Second Myeloid Malignancies in a Large Cohort of Patients With Chronic
      Lymphocytic Leukemia: A Single Institution Experience.
AB  - Patients with chronic lymphocytic leukemia (CLL) have a 2- to 5-fold risk of
      developing a second malignancy compared with the general population. The
      incidence of myeloid malignancies, such as acute myeloid leukemia and
      myelodysplastic syndrome, is increased in CLL and has been linked to previous
      therapy. In this study, we aim at describing characteristics and determining risk
      factors for developing second myeloid disorders (SMDs) in patients with CLL. From
      a total of 1269 patients diagnosed with CLL during the study time period, 30
      (2.4%) were found to have an SMD. The majority of SMDs were myelodysplastic
      syndrome or acute myeloid leukemia (76.7%). The median time from diagnosis of CLL
      to diagnosis of SMD was 4.47 years. Most patients who developed an SMD had
      received treatment for their CLL (86%). The median time from treatment of CLL to
      diagnosis of SMD was 4.19 years. The overall survival of patients with CLL with
      no second malignancy was significantly longer than those with an SMD (11.9 vs.
      7.1 years, P = .001). There was no association between developing SMD and age,
      gender, expression of CD38, expression of ZAP-70, and unmutated immunoglobulin
      heavy chain gene status. The risk of developing SMD in our cohort was higher in
      patients who received fludarabine- or alkylator-based therapy. Our analysis is
      one of the largest series showing that patients receiving fludarabine or
      alkylator-based therapies for CLL have a higher risk of developing SMD. Our study
      also confirms previous reports that prognostic factors in CLL do not increase the
      risk for development of SMD. Clinicians should understand the leukemogenicity of
      fludarabine or alkylator-based treatments when considering treatments for
      patients with CLL.

PMID- 26297267
TI  - Transformative Clinical Trials in Non-Hodgkin and Hodgkin Lymphomas.
AB  - Dramatic progress in the understanding of underlying disease biology and the
      development of novel therapeutics has yielded a revolution that is poised to
      transform the face of lymphoma treatment across a broad spectrum of histologies.
      Ongoing randomized clinical trials are poised to unseat long-entrenched standards
      of care in diffuse large B-cell lymphoma, follicular lymphoma, mantle cell
      lymphoma, peripheral T-cell lymphoma, and Hodgkin lymphoma. Emerging treatment
      approaches are reviewed, including optimization of existing chemoimmunotherapy
      platforms, development of chemotherapy-sparing immunotherapy for follicular
      lymphoma, biologically targeted therapy for subsets of diffuse large B-cell
      lymphoma, and incorporation of novel agents into the treatment of mantle cell
      lymphoma and peripheral T-cell lymphoma. Novel therapies in early stage trials
      with future promise of redefining standards of care are also reviewed for non
      Hodgkin and Hodgkin lymphomas, including small molecule pathway inhibitors and
      advances in immunotherapy. 

PMID- 26297268
TI  - Hemophagocytic Lymphohistiocytosis in Malignant Hematology: Uncommon but Should
      Not Be Forgotten?
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening syndrome of
      excessive immune activation and an inflammatory cytokine storm leading to
      multiple organ failure. We report our experience in a large tertiary referral
      center on HLH in the setting of hematologic malignancies and describe responses
      to therapy and outcomes. Seventeen cases of HLH were included in which the most
      common underlying diagnosis was aggressive lymphoma (n = 7). The median time from
      diagnosis of primary hematologic condition to HLH was 3.1 months. The most common
      presenting features were fever (n = 15), splenomegaly (n = 13), and transaminitis
      (n = 14). The mean serum ferritin level was 21,000 ng/mL. Fourteen patients
      demonstrated evidence of hemophagocytosis in bone marrow or other organs. Among
      all patients, 12 received etoposide, 14 received dexamethasone, and 3 received
      cyclosporine. Intrathecal chemotherapy was administered to 3 patients. Overall, 7
      patients (41%) responded to treatment with clinical and laboratory improvement.
      The median overall survival (OS) from the time of HLH diagnosis and the primary
      hematologic diagnosis was 8.4 months and 29.5 months, respectively. The OS was
      better among patients with HLH with aggressive lymphomas (12 months). Response to
      treatment was associated with better OS. Recognition of manifestations and prompt
      diagnosis of HLH are crucial to initiate prompt therapy and improve outcome.

PMID- 26297269
TI  - Imbalance of Pro- and Anti-Inflammatory Cytokines in Patients With cHL Persists
      Despite Treatment Compared With Control Subjects.
AB  - BACKGROUND: Classical Hodgkin lymphoma (cHL) is a malignant lymphoma that most
      commonly affects young adults. The lymphomagenesis of cHL depends largely on
      immune alterations that contribute to proliferation and maintenance of the
      Hodgkin-Reed-Sternberg (HRS) neoplastic cells. A combination of different immune
      processes is responsible for the escape of HRS cells, the imbalance between pro-
      and anti-inflammatory cytokines being one of them. In this study, we aimed to
      measure serum levels of pro- and anti-inflammatory cytokines in cHL patients
      before and after treatment compared with a healthy controls group, and to
      investigate associations with clinical and pathologic characteristics. PATIENTS
      AND METHODS: We prospectively studied all cases of cHL diagnosed between March
      2009 to March 2013 at the Universidade Federal de Sao Paulo and Hospital Santa
      Marcelina, in Sao Paulo, Brazil. Twenty-nine cases with sufficient clinical data
      were included in this study. Additionally, 18 healthy control subjects were
      included and recruited from our University Blood Bank. Serum cytokine levels of
      interleukin (IL)-2, IL-4, IL-5, IL-6, IL-10, IL-17, tumor necrosis factor (TNF)
      alpha, soluble IL-2 receptor (sCD25), vascular endothelial growth factor (VEGF),
      and interferon (IFN)-gamma were determined in serum of patients and controls
      using a multiplexed immunoassay system. RESULTS: Higher International Prognostic
      Score was positively correlated with increased levels of IL-6 (P = .003); sCD25
      levels were higher in patients with low serum albumin (P = .04), and IFN-gamma
      seemed to correlate with B symptoms, although did not reach statistical
      significance (P = .057). Pretreatment levels of IL-10, IL-6, TNF-alpha, and sCD25
      were increased in cHL patients compared with in healthy control subjects (P <
      .001), with median values of 7 pg/mL (range, 0.3-230.9), 5.3 pg/mL (range, 0.4
      72.7), 14.6 (range, 4.0-60.4), and 575.9 pg/mL (range, 7.5-1813.3), respectively.
      Treatment significantly reduced levels of IL-10 (7.0 to 0.3; P < .001), IL-6 (5.3
      to 0.4; P = .014), and sCD25 (575.9 to 93.5; P < .001), however, levels of IL-4
      increased (0.6 to 2.2; P = .002). Compared with normal control subjects,
      increased levels of IL-6 (0.4 to 0.4; P = .027), sCD25 (93.5 to 7.5; P = .002),
      and TNF-alpha (12 to 8.7; P = .003) persisted after treatment. CONCLUSION: In
      this study we showed higher levels of IL-6, IL-10, TNF-alpha, and sCD25 in cHL
      patients at diagnosis than in healthy control subjects. After treatment, levels
      of IL-6, IL-10, and sCD25 decreased gradually but did not normalize.
      Understanding the cytokine pattern is extremely important in the development of
      future therapies that target interactions between neoplastic cells and the
      inflammatory microenvironment.

PMID- 26297270
TI  - Ocular Adnexal Lymphomas: Single-Center Experience.
AB  - Ocular adnexal lymphoma (OAL) is a rare manifestation of non-Hodgkin lymphoma
      consisting of the tissues and structures surrounding the eye that include the
      conjunctiva, eyelids, lacrimal gland, and orbital soft tissues. OAL comprise 1%
      to 2% of all non-Hodgkin lymphomas and about 8% of the extranodal lymphomas;
      however, the incidence of OAL has increased by approximately 6% annually in last
      2 decades, and OAL now represents the majority of orbital malignancies. There are
      no uniform treatment guidelines for OAL. Because of high local and extraorbital
      recurrence rates, appropriate local, systemic, or combined treatment must be
      applied. 

PMID- 26297271
TI  - Investigating the Role of JAK/STAT Pathway on Dasatinib-Induced Apoptosis for CML
      Cell Model K562.
AB  - We aimed to evaluate the cytotoxic and apoptotic effects of dasatinib (BMS
      354825) on K562 chronic myeloid leukemia (CML) cells and to examine the roles of
      STAT genes on dasatinib-induced apoptosis. The results showed that dasatinib
      decreased proliferation and induced apoptosis in K562 cells in a dose- and time
      dependent manner. mRNA and protein levels of STAT5A and STAT5B genes were
      significantly reduced in dasatinib-treated K562 cells. These data indicated that
      STAT inhibition by dasatinib might be therapeutic in JAK/STAT pathway-associated
      malignancies after confirmation with clinical studies. 

PMID- 26297273
TI  - How We Treat Myeloproliferative Neoplasms.
AB  - The present report focuses on management strategies for the myeloproliferative
      neoplasm according to the structure and processes we use within our center, a
      large tertiary unit in central London. The standard procedures for achieving an
      accurate diagnosis and risk stratification and therapeutic strategies for these
      diseases with a detailed focus on contentious areas are discussed. In the 9 years
      after the description of the Janus kinase 2 mutation, this field has altered
      quite radically in several aspects. For example, a new therapeutic paradigm
      exists, especially for myelofibrosis. We share how our unit has adapted to these
      changes. 

PMID- 26297272
TI  - Pre-clinical Specificity and Safety of UC-961, a First-In-Class Monoclonal
      Antibody Targeting ROR1.
AB  - Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncoembryonic
      antigen. Because of its expression on the cell surface of leukemia cells from
      patients with chronic lymphocytic leukemia (CLL), but not on normal B-cells or
      other postpartum tissues, ROR1 is an attractive candidate for targeted therapies.
      UC-961 is a first-in-class humanized monoclonal antibody that binds the
      extracellular domain of ROR1. In this article we outline some of the preclinical
      studies leading to an investigational new drug designation, enabling clinical
      studies in patients with CLL. 

PMID- 26297274
TI  - Minimal Residual Disease in AML: Why Has It Lagged Behind Pediatric ALL?
AB  - Although the concept of minimal residual disease (MRD) as an indicator for the
      quality of treatment response is the same in acute myeloid leukemia (AML) and
      acute lymphoid leukemia (ALL), the practice of measuring MRD levels for
      monitoring response and guiding therapy after induction has been implemented much
      more rapidly in ALL, particularly pediatric ALL, than in AML. In this perspective
      we examine the facts and discuss why ALL appears to be more amenable to MRD
      shaped risk allocation and a revised definition of complete remission. 

PMID- 26297276
TI  - Janus Kinase Inhibitors and Stem Cell Transplantation in Myelofibrosis.
AB  - Myelofibrosis (MF) is characterized by splenomegaly, blood count abnormalities,
      particularly cytopenias, and a propensity for transformation to acute leukemia.
      The current treatment approach is to ameliorate symptoms due to these
      abnormalities. Treatment with Janus kinase 2 inhibitors reduces spleen size and
      improves symptoms in patients with MF, but most of the patients eventually have
      disease progression and stop responding. Allogeneic stem cell transplantation
      remains the only curative option. However, its efficacy must be balanced against
      the risk of treatment-related death and long-term sequelae of transplant like
      chronic graft versus host disease. The challenge is to integrate treatment with
      Janus kinase inhibitors with allogeneic stem cell transplantation. 

PMID- 26297277
TI  - Which Patients Should Undergo Allogeneic Stem Cell Transplantation for
      Myelodysplastic Syndromes, and When Should We Do It?
AB  - Allogeneic hematopoietic stem cell transplantation (SCT) can cure a proportion of
      patients with myelodysplastic syndromes (MDS). However, treatment related
      toxicities, graft versus host disease, infectious complications and relapse
      remain major problems post transplant. Further, recent new developments with
      innovative drugs including hypomethylating agents (HMA) have extended the
      therapeutic alternatives for our patients. Nevertheless, with the introduction of
      reduced-intensity conditioning and thereby reducing early mortality, transplant
      numbers in MDS patients have significantly increased recently. In the absence of
      prospective randomized trials emphasis should be put on patient selection and
      optimization of the pre- and post-transplant treatment in order to achieve long
      term disease control and at the same time maintain an adequate quality of life.
      With better understanding of disease biology and prognosis and with different
      types of conditioning regimens as well as different graft sources, a transplant
      strategy should be tailored to the individual host to maximize the benefits of
      this procedure. 

PMID- 26297275
TI  - New Therapeutic Approaches in Polycythemia Vera.
AB  - Polycythemia vera (PV) is 1 of the 3 Philadelphia-negative myeloproliferative
      neoplasms. Clinically, PV is an indolent disease, but its course can be
      complicated by arterial and venous vascular incidents, evolution to
      myelofibrosis, or leukemic transformation. Treatment of PV is therefore aimed at
      preventing such acute complications. The cornerstone of therapy of low-risk
      patients remains strict control of cardiovascular risk factors, the use of
      phlebotomy, and low-dose aspirin. Higher-risk patients should also receive
      cytoreductive treatments. Hydroxyurea and interferon alpha represent standard
      first-line options for newly diagnosed high-risk PV patients. Recommendations for
      patients whose disease fails to respond to these therapies are less clearly
      defined. The discovery of a mutation in the Janus kinase (JAK) 2 gene (V617F) in
      almost all cases of PV has prompted the development of molecularly targeted
      agents for the treatment of these patients. In this review, we discuss key
      clinical aspects, the current therapeutic armamentarium, and data on the use of
      novel agents in patients with PV. 

PMID- 26297278
TI  - Transformation of the Clinical Management of CMML Patients Through In-Depth
      Molecular Characterization.
AB  - Chronic myelomonocytic leukemia (CMML) has been recently recognized as a
      clinically and biologically unique disease. Although this clinical distinction
      was solidified in 2008 by the World Health Organization, the individual
      properties that biologically confirm CMML to be ontologically distinct from
      myelodysplastic syndromes have only been discovered with recent comprehensive
      molecular characterization. Incorporation of next-generation platforms has
      allowed for the identification of mutations in most patients, which has broad
      applicability in the clinical management of CMML, especially in the context of
      diagnosis and prognosis. Future goals of research should include the development
      of CMML-specific disease-modifying therapies and further genetic understanding of
      this disease will likely become the foundation for these efforts. 

PMID- 26297279
TI  - Treatment of Higher-Risk Myelodysplastic Syndromes After Failure of
      Hypomethylating Agents.
AB  - Hypomethylating agents (HMAs) are the standard of care for higher-risk
      myelodysplastic syndrome (MDS) patients in whom azacitidine was the only
      treatment to demonstrate an overall survival advantage in a randomized clinical
      study. Only 40% to 50% of patients typically will respond to HMAs, with a median
      duration of response < 1.5 years and eventually all patients will lose initial
      response. Outcome after HMA treatment failure is poor and represents an unmet
      need. In this article we review the definition of HMA failure in higher-risk MDS
      patients and its outcome. We highlight options of treatment including sequential
      use of HMAs, add-back strategies, other palliative chemotherapy options, and
      provide an overview for several promising investigational agents. Understanding
      mechanisms of resistance and molecular changes at the time of HMA failure will be
      a key to development of further therapies.

PMID- 26297280
TI  - Validation of the Lower-Risk MD Anderson Prognostic Scoring System for Patients
      With Myelodysplastic Syndrome.
AB  - The International Prognostic Scoring System (IPSS) is the most widely used tool
      for risk assessment and treatment decisions for myelodysplastic syndrome (MDS).
      Several new models have been proposed to identify a subset of lower-risk patients
      with MDS who are experiencing inferior than expected outcomes. We validated the
      Lower-Risk MD Anderson Risk Model (LR-MDAS) in 1288 lower-risk patients with MDS
      by the IPSS. On the basis of the LR-MDAS, 228 patients (17%) were in category 1,
      730 patients (57%) were in category 2, 315 patients (25%) were in category 3, and
      15 patients (1%) were in an unknown category. The median overall survival for the
      corresponding LR-MDAS categories was (1) 109 months (95% confidence interval
      [CI], 82-137), (2) 56 months (95% CI, 58-73), and (3) 29 months (95% CI, 24-35)
      (P < .005). Overall, 25% of patients were upstaged to category 3. LR-MDAS refined
      prognostic value among very low-, low-, and intermediate-risk Revised IPSS. The
      rate of acute myeloid leukemia transformation according to LR-MDAS was 15%, 18%,
      and 29% for categories 1, 2, and 3, respectively (P < .005). Our data validate
      the prognostic value of the LR-MDAS model, but the utility of it as a treatment
      decision tool should be studied prospectively.

PMID- 26297281
TI  - Practical Management of Lenalidomide-Related Rash.
AB  - Lenalidomide (LEN) is an immunomodulatory drug with US Food and Drug
      Administration approval for use in myelodysplastic syndromes (MDS), multiple
      myeloma (MM), and mantle cell lymphoma (MCL). The toxicity profile for LEN is
      similar across indications, with the most common adverse events reported in
      registration trials being hematologic in nature, and Grade >= 3 hematologic
      toxicities the most common reasons for treatment interruption or permanent LEN
      discontinuation. However, an analysis of the Celgene Global Drug Safety database
      showed that nonserious rash was the leading cause of permanent early
      discontinuation of LEN in patients with MDS treated in the postmarketing setting
      (similar data not available for patients with MM or MCL). In registration trials,
      rash was reported in up to a third of patients, but Grade >= 3 rash was uncommon
      and rash rarely led to LEN treatment interruption or permanent discontinuation.
      This suggests differences in management of LEN-related rash in clinical trials
      versus real-world use. Most LEN-related rash is mild to moderate in severity and
      might present as patchy, raised, macular skin lesions, sometimes with localized
      urticaria, which might be associated with pruritus. Mild to moderate rash might
      be treated with topical corticosteroids and/or oral antihistamines. Any grade LEN
      related rash should be appropriately managed through awareness of symptoms,
      appropriate and prompt intervention, and maximizing patient self-reporting of
      early signs of rash using upfront educational initiatives. This guide to
      management of LEN-related rash reviews key clinical data from registration
      trials, and the incidence and physiology of LEN-related rash, grading of rash,
      and guidelines for patients and caregivers.

PMID- 26297282
TI  - Effect of Initial Body Mass Index on Survival Outcome of Patients With Acute
      Leukemia: A Single-Center Retrospective Study.
AB  - BACKGROUND: Obesity is associated with an increased risk of mortality from
      cardiovascular causes and occurrence of malignancies. However, the effect of body
      mass index (BMI) on survival outcome remains controversial in acute leukemia (AL)
      patients. PATIENTS AND METHODS: A total of 531 adults with AL who entered
      clinical trials in our institution between 1994 and 2012 were analyzed
      retrospectively for the effect of BMI at diagnosis on outcome. The median follow
      up was 4.7 years (95% confidence interval [CI], 4.0-5.1). RESULTS: BMI had no
      significant effect on complete response rate, disease-free survival (DFS), or
      overall survival (OS) in patients from the whole cohort when considering a cutoff
      value for BMI of 25, and when analyzed according to age, or initial cytogenetics.
      In T-acute lymphoblastic leukemia (T-ALL) patients with BMI > 25, median DFS was
      not reached with a 3-year DFS at 76%, and median DFS was 16.1 months with 3-year
      DFS at 13% for those with BMI <= 25 (P = .005). Median OS was not reached in T
      ALL patients with BMI > 25 versus 28.3 months in those with BMI <= 25 (3-year OS:
      78% vs. 41%; P = .04). Multivariate analyses confirmed the prognostic value of
      BMI (> 25 vs. < 25) in T-ALL, but only in terms of DFS (hazard ratio, 0.25; 95%
      CI, 0.05-0.87; P = .037). However, in a validation cohort of 211 T-ALL patients,
      these results were not confirmed. CONCLUSION: Results from the literature are
      very heterogeneous and contradictory regarding the effect of BMI on leukemia
      outcome. Even if nutritional status during chemotherapy courses is critical,
      these findings provide further evidence that initial body size does not have a
      major prognostic effect on survival in AL patients.

PMID- 26297283
TI  - Allogeneic Transplantation for Unfavorable-Risk Acute Myeloid Leukemia.
AB  - Acute myeloid leukemia (AML) is a complex, heterogeneous disorder that can have
      devastating effects. Although control of AML can be attained with various
      induction regimens, long-term cure is much more difficult to maintain. This is
      understated in patients with unfavorable-risk AML, who are usually older and have
      prior myeloid and/or therapy-related disease and more challenges in curing this
      disease. 

PMID- 26297285
TI  - Assessment of Molecular Markers in AML Patients: A Hospital-Based Study in
      Lebanon.
AB  - BACKGROUND: In the past, research has been focused on elucidating the molecular
      genetics and epigenetic basis of acute myelogenous leukemia (AML). This has led
      to the change in the classification and management of AML patients. Because no
      molecular studies regarding AML characterization in Lebanese patients had yet
      been reported, we decided to determine in our institution the prevalence of the
      recurrent genetic rearrangements t(8;21), inv(16), t(15;17) and Fms-like (Suzanne
      McDonough feline sarcoma) tyrosine kinase 3 (FLT3) and nucleophosmin (NPM1)
      mutations. MATERIALS AND METHODS: Fusion gene transcripts from chromosome
      aberrations were analyzed according to standardized reverse transcription
      polymerase chain reactions after the report of BIOMED-1 concerted action:
      investigation of minimal residual disease in acute leukemia. FLT3 and NPM1
      mutations were screened using home-brew methodologies. RESULTS: We reviewed 144
      bone marrow samples from AML patients referred to Saint George Hospital for
      molecular and cytogenetic studies from September 2006 to July 2014. The male to
      female patient ratio was 1.34 to 1. We detected the inv(16) in 6 patients [4.2%]
      (type A, 5 [83%]; type D, 1 [17%]), t(8;21) in 7 patients [4.9%] (e5e2), and
      t(15;17) in 36 patients [25.0%] (24 [67%] breakpoint cluster region 1 (bcr1), 12
      [33%] bcr3). Other chromosomal abnormalities (trisomy 8, complex karyotype,
      t(6;9),...) were found in 44 patients [31.4%] and 51 [35.5%] cases showed normal
      karyotype. Among the normal karyotypes, 6 patients [11.8%] were FLT3-positive (4
      [67%] internal tandem duplication [ITD], 2 [33%] D835V), 8 [15.7%] had type A
      NPM1 mutation and 8 [15.7%] type A NPM1 and FLT3/ITD concomitantly. CONCLUSION:
      Our results, except for the prevalence of acute promyelocytic leukemia, are
      concordant with those reported in the literature with approximately 35% of the
      patients cytogenetically normal. Testing patients with normal karyotype for other
      molecular markers such as CCAAT/enhancer-binding protein alpha mutations,
      isocitrate dehydrogenase 1/2 mutations, and mixed lineage leukemia rearrangements
      could therefore provide additional prognostic, predictive, and therapeutic values
      for AML patients.

PMID- 26297284
TI  - Decitabine and Sorafenib Therapy in FLT-3 ITD-Mutant Acute Myeloid Leukemia.
AB  - BACKGROUND: Acute myeloid leukemia (AML) characterized by Feline McDonough
      Sarcoma-like tyrosine kinase-3 (FLT-3) internal tandem duplication (ITD)
      mutations have poor outcomes. Treatment options are limited, because these
      mutations confer resistance to conventional chemotherapy. FLT-3 inhibitors such
      as sorafenib have been studied as a single agent and in combination with
      conventional chemotherapy or azacytidine with fair responses. PATIENTS AND
      METHODS: Here we describe our preclinical and clinical experience with the
      combination of the DNA hypomethylating agent, decitabine and sorafenib for the
      treatment of FLT-3 ITD-mutant AML. RESULTS: In vitro treatment of the human FLT-3
      ITD-mutant AML cell line, MV4-11, with both drugs significantly improved growth
      inhibition over single-agent therapy and resulted in synergistic antitumor
      effects (combination index < 1). A case series of 6 patients treated with off
      protocol combination of decitabine and sorafenib demonstrated overall responses
      in 5 patients (83%) with a median survival of 155 days. Four of the 5 patients
      (80%) with relapsed/refractory AML achieved complete responses with incomplete
      count recovery. The combination was also well tolerated. CONCLUSION: Further
      investigation is warranted to confirm these responses.

PMID- 26297286
TI  - Acute Myeloid Leukemia With t(v;5q33) Is Associated With Poor Overall Survival
      and Often Lacks Myelodysplastic Features.
AB  - BACKGROUND: Acute myeloid leukemia (AML) with specific balanced 5q33
      translocations are classified as AML with myelodysplasia-related changes
      regardless of their morphologic findings or antecedent hematologic disease, but
      the clinicopathologic features of such cases remain poorly understood. MATERIALS
      AND METHODS: From > 2000 cases of hematological malignancies seen at our
      institution between 2000 and 2013, we identified 9 AML patients with 5q33
      translocations with variable partner loci, t(v;5q33). RESULTS: The study group
      included 8 men and 1 woman, with a median age of 64 years (range, 19-87 years).
      Four patients had an antecedent myeloproliferative neoplasm (MPN). Cytogenetic
      analysis showed t(v;5q33) as a sole chromosomal abnormality in 4 (44%) patients,
      t(v;5q33) and del(3)(q21;q26.2) in 1 (11%) patient, and a complex karyotype in 4
      (44%) patients. Only 1 patient had morphologic features of myelodysplasia in 2 or
      more lineages. Follow-up was available for 7 patients and the median overall
      survival (OS) was 12 months. Patients with a history of MPN had a significantly
      shorter OS compared with those with de novo AML (11 vs. 20 months; P = .0445).
      There was no correlation between complex karyotype and OS in this small group of
      AML patients (P = .5904). CONCLUSION: The t(v;5q33) is a rare cytogenetic
      aberration in AML. Although associated with a poor outcome, AML with t(v;5q33)
      usually lacks morphologic evidence of multilineage dysplasia. Patients who have
      AML with t(v;5q33) after MPN have a worse OS compared with those with de novo
      AML.

PMID- 26297287
TI  - Novel Therapeutics for Therapy-Related Acute Myeloid Leukemia: 2014.
AB  - Effective treatment options for adults with therapy-related AML continues to be
      an area of unmet need. Genetic and molecular changes within these leukemias
      confer resistance to standard chemotherapy regimens. Emerging developmental
      therapeutics in this area has focused on several approaches. These include; novel
      delivery of chemotherapy as well as newer DNA-damaging agents delivered through
      antibody-drug conjugates, increased use of hypomethylating agents, and
      molecularly-directed small molecules against specific mutations commonly
      occurring in secondary AML. Results of this efforts are encouraging, but to date,
      no clear improvements have been demonstrated in this most difficult to treat
      population.

PMID- 26297288
TI  - Disseminated Intra-Abdominal Aspergilloma With Abdominal Wall Invasion in a
      Patient With Acute Myeloid Leukemia: A Case Report.

PMID- 26297289
TI  - Distinguishing the Causes of Pulmonary Infiltrates in Patients With Acute
      Leukemia.
AB  - Pulmonary infiltrates are commonly observed in patients with acute leukemia (AL),
      particularly acute myeloid leukemia, who undergo remission induction therapy. The
      mortality rate is unacceptably high and depends on 3 factors: the host
      (performance status, comorbidities, and frailty), the etiology of the infiltrates
      and the type of response to antileukemic therapy. The approach to the diagnosis
      of pulmonary infiltrates in patients with AL includes a medical history, thorough
      physical examination, radiologic pattern of the infiltrates (focal vs. diffuse),
      and timing of their appearance in relation to the start of antileukemic therapy
      (early, ie, within the first 2 weeks or late). Localized infiltrates are most
      commonly caused by bacterial (early) and fungal infections (late). Diffuse early
      infiltrates might be caused by leukemic infiltration of the lungs, pulmonary
      hemorrhage and/or edema, diffuse alveolar damage, viral pneumonia, and rarely
      transfusion-related acute lung injury (TRALI) or the differentiation syndrome.
      Similar to the early phase, pulmonary edema, viral pneumonia, and rarely TRALI
      might cause diffuse infiltrates during the late phase, in addition to immune
      reconstitution and pneumocystosis, particularly among patients with acute
      lymphoblastic leukemia. Diagnostic tests, invasive and noninvasive, can be
      particularly useful to establish the diagnosis. Early intervention is critical
      and is based on the most likely diagnosis with modification when the etiology is
      confirmed. 

PMID- 26297290
TI  - Mannose-binding Lectin (MBL) as a susceptible host factor influencing Indian
      Visceral Leishmaniasis.
AB  - Visceral Leishmaniasis (VL), caused by Leishmania donovani is endemic in the
      Indian sub-continent. Mannose-binding Lectin (MBL) is a complement lectin protein
      that binds to the surface of Leishmania promastigotes and results in activation
      of the complement lectin cascade. We utilized samples of 218 VL patients and 215
      healthy controls from an Indian population. MBL2 functional variants were
      genotyped and the circulating MBL serum levels were measured. MBL serum levels
      were elevated in patients compared to the healthy controls (adjusted P=0.007).
      The MBL2 promoter variants -78C/T and +4P/Q were significantly associated with
      relative protection to VL (-78C/T, OR=0.7, 95% CI=0.5-0.96, adjusted P=0.026 and
      +4P/Q, OR=0.66, 95% CI=0.48-0.9, adjusted P=0.012). MBL2*LYQA haplotypes occurred
      frequently among controls (OR=0.69, 95% CI=0.5-0.97, adjusted P=0.034). MBL
      recognizes Leishmania and plays a relative role in establishing L. donovani
      infection and subsequent disease progression. In conclusion, MBL2 functional
      variants were associated with VL. 

PMID- 26297292
TI  - TWIST1 and TWIST2 regulate glycogen storage and inflammatory genes in skeletal
      muscle.

PMID- 26297291
TI  - Enhanced intestinal epithelial cell proliferation in diabetic rats correlates
      with beta-catenin accumulation.
AB  - The Wnt/beta-catenin signaling cascade is implicated in the control of stem cell
      activity, cell proliferation, and cell survival of the gastrointestinal
      epithelium. Recent evidence indicates that the Wnt/beta-catenin pathway is
      activated under diabetic conditions. The purpose of this study was to evaluate
      the role of Wnt/beta-catenin signaling during diabetes-induced enteropathy in a
      rat model. Male rats were divided into three groups: control rats received
      injections of vehicle; diabetic rats received injections of one dose of
      streptozotocin (STZ); and diabetic-insulin rats received injections of STZ and
      were treated with insulin given subcutaneously at a dose of 1 U/kg twice daily.
      Rats were killed on day 7. Wnt/beta-catenin-related genes and expression of
      proteins was determined using real-time PCR, western blotting, and
      immunohistochemistry. Among 13 genes identified by real-time PCR, seven genes
      were upregulated in diabetic rats compared with control animals including the
      target genes c-Myc and Tcf4. Diabetic rats also showed a significant increase in
      beta-catenin protein compared with control animals. Treatment of diabetic rats
      attenuated the stimulating effect of diabetes on intestinal cell proliferation
      and Wnt/beta-catenin signaling. In conclusion, enhanced intestinal epithelial
      cell proliferation in diabetic rats correlates with beta-catenin accumulation. 

PMID- 26297293
TI  - Nocardia halotolerans sp. nov., a halotolerant actinomycete isolated from saline
      soil.
AB  - A novel halotolerant actinomycete, strain Chem15(T), was isolated from soil
      around Inche-Broun hypersaline wetland; its taxonomic position was determined
      based on a polyphasic approach. Strain Chem15(T) was strictly aerobic and
      tolerated NaCl up to 12.5%. The optimum temperature and pH for growth were 28-30 
      degrees C and pH 7.0-7.5, respectively. The cell wall of strain Chem15(T)
      contained meso-diaminopimelic acid as diamino acid and galactose, arabinose and
      ribose as whole-cell sugars. The major phospholipids were diphosphatidylglycerol,
      phosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and
      phosphatidylinositol mannosides. The cellular fatty acids profile consisted of
      C16 : 0, iso-C18 : 0, C18 : 0 10-methyl and C18 : 1omega9c, and the major
      respiratory quinone was MK-8(H4cycl). The G+C content of the genomic DNA was 68.0
      mol%. The novel strain constituted a distinct phyletic line within the genus
      Nocardia, based on 16S rRNA gene sequence analysis, and was closely associated
      with Nocardia sungurluensis DSM 45714(T) and Nocardia alba DSM 44684(T) (98.2 and
      98.1% 16S rRNA gene sequence similarity, respectively). However DNA-DNA
      relatedness and phenotypic data demonstrated that strain Chem15(T) was clearly
      different from closely related species of the genus Nocardia. It is concluded
      that the organism should be classified as a representative of a novel species of
      the genus Nocardia, for which the name Nocardia halotolerans sp. nov. is
      proposed. The type strain is Chem15(T) ( = IBRC-M 10490(T) = LMG 28544(T)).

PMID- 26297294
TI  - Effects of microvascular decompression surgery on posture control: A case report
      in an elderly patient.
AB  - AIMS OF THE STUDY: We report the case of an 84-year-old woman with neurovascular
      conflict of the left cochleovestibular nerve. Prior to surgery, the patient
      complained of positional vertigo and dizziness for the past two years, and marked
      instability. Hearing loss and tinnitus were reported on the left side. The aim of
      this study was to investigate the effects of microvascular decompression of the
      cochleovestibular nerve on posture control. MATERIALS AND METHODS: Evaluation of
      cochleovestibular function and posture control was performed before and after
      surgery. Postural performance was analyzed in static and dynamic conditions, with
      and without vision, and with optokinetic stimulation. Perception of the static
      visual vertical (SVV) was recorded in darkness. RESULTS: Positional vertigo and
      tinnitus disappeared immediately after the decompression. The SVV remained
      unchanged one week after the surgery. Speech intelligibility of the left ear was
      improved (30 dB), and the vestibular deficit on this side was also significantly
      reduced (54% versus 18%). However, the more spectacular result was the effect on
      postural control. This elderly patient improved her postural balance in both
      static and dynamic conditions, and became able to maintain her equilibrium in the
      more challenging dynamic conditions, with and without vision, as early as one
      week after the surgery, a postural performance that she had been unable to do
      preoperatively. CONCLUSION: This work is the first to show that the postural
      deficits resulting from neurovascular conflict of the cochleovestibular nerve are
      strongly improved after microvascular decompression.

PMID- 26297295
TI  - Sequential (as Opposed to Simultaneous) Antibiotic Therapy Improves Helicobacter
      pylori Eradication in the Pediatric Population: A Meta-Analysis.
AB  - Helicobacter pylori is a common infection associated with many gastrointestinal
      diseases. Triple or quadruple therapy is the current recommendation for H pylori
      eradication in children but is associated with success rates as low as 50%.
      Recent studies have demonstrated that a 10-day sequential therapy regimen, rather
      than simultaneous antibiotic administration, achieved eradication rates of nearly
      95%. This meta-analysis found that sequential therapy increased eradication rates
      by 14.2% (relative risk [RR] = 1.142; 95% confidence interval [CI] = 1.082-1.207;
      P < .001). Ten-day sequential therapy significantly improved H pylori eradication
      rates compared to the 7-day standard therapy (RR = 1.182; 95% CI = 1.102-1.269; p
      < .001) and 10-day standard therapy (RR = 1.179; 95% CI = 1.074-1.295; P = .001),
      but had lower eradication rates compared to 14-day standard therapy (RR = 0.926;
      95% CI = 0.811-1.059; P = .261). The use of sequential therapy is associated with
      increased H pylori eradication rates in children compared to standard therapy of
      equal or shorter duration. 

PMID- 26297296
TI  - Predictors of cessation in smokers suspected of TB: Secondary analysis of data
      from a cluster randomized controlled trial.
AB  - BACKGROUND: Smoking cessation services are rarely found within health services in
      low income countries. Given the interactions between Tuberculosis (TB) and
      tobacco, including cessation support within TB programs offers a promising cost
      effective solution. We conducted secondary analysis of data from a cluster
      randomized controlled trial of smoking cessation in health centers in Pakistan to
      identify predictors of continuous and short-term abstinence in smokers suspected
      of TB using cigarettes or hookah. METHODS: Predictor variables of those
      continuously abstinent at 5 and 25 weeks post quit-date (continuous abstinence)
      and those abstinent only at 5 weeks (short-term abstinence) were compared with
      those who continued smoking and with each other. Self-reported abstinence at both
      time points was confirmed biochemically. RESULTS: Data obtained from 1955 trial
      participants were analyzed. The factors that predicted continued smoking when
      compared to continuous abstinence were: being older RR 0.97 (0.95 to 0.98),
      smoking higher quantities of tobacco RR 0.975 (0.97 to 0.98) and sharing a
      workplace with other smokers RR 0.88 (0.77 to 0.99). Those with a confirmed TB
      diagnosis were more likely to remain continuously abstinent than those without RR
      1.27 (1.10-1.47). CONCLUSIONS: Those diagnosed with TB are more likely to be
      abstinent than those diagnosed with other respiratory conditions. Beyond this,
      predictors of continued smoking in Pakistan are similar to those in high income
      contexts. Taking advantage of the 'teachable moment' that a TB diagnosis provides
      is an efficient means for resource-poor TB programs in low income settings to
      increase tobacco cessation and improve health outcomes.

PMID- 26297297
TI  - The remote brief intervention and referral to treatment model: Development,
      functionality, acceptability, and feasibility.
AB  - BACKGROUND: Screening, brief intervention, and referral to treatment (SBIRT) is
      effective for reducing risky alcohol use across a variety of medical settings.
      However, most programs have been unsustainable because of cost and time demands.
      Telehealth may alleviate on-site clinician burden. This exploratory study
      examines the feasibility of a new Remote Brief Intervention and Referral to
      Treatment (R-BIRT) model. METHODS: Eligible emergency department (ED) patients
      were enrolled into one of five models. (1) Warm Handoff: clinician-facilitated
      phone call during ED visit. (2) Patient Direct: patient-initiated call during
      visit. (3) Electronic Referral: patient contacted by R-BIRT personnel post visit.
      (4) Patient Choice: choice of models 1-3. (5) Modified Patient Choice: choice of
      models 1-2, Electronic Referral offered if 1-2 were declined. Once connected, a
      health coach offered assessment, counseling, and referral to treatment. Follow up
      assessments were conducted at 1 and 3 months. Primary outcomes measured were
      acceptance, satisfaction, and completion rates. RESULTS: Of 125 eligible
      patients, 50 were enrolled, for an acceptance rate of 40%. Feedback and
      satisfaction ratings were generally positive. Completion rates were 58% overall,
      with patients enrolled into a model wherein the consultation occurred during the
      ED visit, as opposed to after the visit, much more likely to complete a
      consultation, 90% vs. 10%, chi(2) (4, N=50)=34.8, p<0.001. CONCLUSIONS: The R
      BIRT offers a feasible alternative to in-person alcohol SBIRT and should be
      studied further. The public health impact of having accessible, sustainable,
      evidence-based SBIRT for substance use across a range of medical settings could
      be considerable.

PMID- 26297298
TI  - Differential expression of alpha-synuclein splice variants in the brain of
      alcohol misusers: Influence of genotype.
AB  - BACKGROUND: Chronic alcohol misuse causes damage in the central nervous system
      that may lead to tolerance, craving and dependence. These behavioural changes are
      likely the result of cellular adaptations that include changes in gene
      expression. alpha-Synuclein is involved in the dopaminergic reward pathway, where
      it regulates dopamine synthesis and release. Previous studies have found that the
      gene for alpha-synuclein, SNCA, is differentially expressed in alcohol misusers.
      METHODS: The present study measured the expression of three alpha-synuclein
      variants, SNCA-140, SNCA-112, and SNCA-115 in the prefrontal cortex of controls
      and alcohol misusers with and without cirrhosis of the liver. In addition, eight
      SNPs located in the 5'- and 3'-UTRs were genotyped in a Caucasian population of
      125 controls and 115 alcohol misusers. RESULTS: The expression of SNCA-140 and
      SNCA-112 was significantly lower in alcohol misusers with cirrhosis than in
      controls. However, SNCA-115 expression was significantly greater in alcohol
      misusers with cirrhosis than in controls. Allele and genotype frequencies
      differed significantly between alcohol misusers and controls for three SNPs,
      rs356221, rs356219 and rs2736995. Two SNPs, rs356221 and rs356219, were in high
      linkage disequilibrium. There was no increased risk of alcoholism associated with
      specific genotypes or haplotypes. Our results suggest that the rs356219/356221 G
      A haplotype may decrease the chance of having an alcohol misuse phenotype.
      CONCLUSION: These findings suggest that alcohol misuse may alter the expression
      of the individual alpha-synuclein splice variants differently in human brain.
      There was no evidence of an effect of sequence variation on the expression of
      alpha-synuclein splice variants in this population.

PMID- 26297299
TI  - Special Issue on fate and transport of biocolloids and nanoparticles in soil and
      groundwater systems.

PMID- 26297300
TI  - Reprint of "Abstraction for data integration: Fusing mammalian molecular,
      cellular and phenotype big datasets for better knowledge extraction".
AB  - With advances in genomics, transcriptomics, metabolomics and proteomics, and more
      expansive electronic clinical record monitoring, as well as advances in
      computation, we have entered the Big Data era in biomedical research. Data
      gathering is growing rapidly while only a small fraction of this data is
      converted to useful knowledge or reused in future studies. To improve this, an
      important concept that is often overlooked is data abstraction. To fuse and reuse
      biomedical datasets from diverse resources, data abstraction is frequently
      required. Here we summarize some of the major Big Data biomedical research
      resources for genomics, proteomics and phenotype data, collected from mammalian
      cells, tissues and organisms. We then suggest simple data abstraction methods for
      fusing this diverse but related data. Finally, we demonstrate examples of the
      potential utility of such data integration efforts, while warning about the
      inherit biases that exist within such data. 

PMID- 26297302
TI  - Synergistic antinociceptive interaction between palmitoylethanolamide and
      tramadol in the mouse formalin test.
AB  - Pharmacological synergism has been used to obtain a higher efficacy using drug
      concentrations at which side effects are minimal. In this study, the
      pharmacological antinociceptive interaction between N-palmitoylethanolamide (PEA)
      and tramadol was investigated. The individual concentration-response curves for
      PEA (0.1-56.2 MUg/paw) and tramadol (1-56.2 MUg/paw) were evaluated in mice in
      which nociception was induced by an intraplantar injection of 2% formalin.
      Isobolographic analysis was used to evaluate the pharmacological interaction
      between PEA (EC50=23.7+/-1.6 MUg/paw) and tramadol (EC50=26.02+/-2.96 MUg/paw)
      using the EC50 and a fixed 1:1 ratio combination. The isobologram demonstrated
      that the combinations investigated in this study produced a synergistic
      interaction; the experimental values (Zexp=9.5+/-0.2 MUg/paw) were significantly
      smaller than those calculated theoretically (Zadd=24.8+/-0.2 MUg/paw). The
      antinociceptive mechanisms of the PEA and tramadol combination involved the
      opioid receptor, transient receptor potential cation channel subfamily V member 1
      (TRPV1), and peroxisome proliferator-activated receptor alpha (PPAR-alpha). The
      sedative effect of the combination of PEA and tramadol was less than that
      generated by individual treatments. These findings suggest that the PEA and
      tramadol combination produced enhanced antinociceptive efficacy at concentrations
      at which side effects are minimal.

PMID- 26297303
TI  - Atractylenolide I protects mice from lipopolysaccharide-induced acute lung
      injury.
AB  - Atractylenolide I (AO-I), one of the major bioactive components isolated from
      Rhizoma Atractylodes macrocephala, has been reported to have anti-inflammatory
      effects. In the present study, we investigated the protective effects of AO-I on
      acute lung injury (ALI) using LPS-induced ALI mouse model. Lung injury was
      assessed by histological study. Inflammatory cytokines TNF-alpha, IL-6 and IL
      1beta production were detected by ELISA. TLR4 expression and NF-kappaB activation
      were measured by western blot analysis. The results showed that treatment of AO-I
      significantly attenuated LPS-induced lung wet-to-dry weight ratio and MPO
      activity. Meanwhile, treatment of AO-I significantly inhibited the production of
      TNF-alpha, IL-6, IL-1beta, IL-13, and MIF production in bronchoalveolar lavage
      fluid (BALF), as well as neutrophils and macrophages in BALF. AO-1 could up
      regulate the production of IL-10 in BALF. Besides, LPS-induced TLR4 expression
      and NF-kappaB activation were suppressed by treatment of AO-I. In conclusion, the
      current study suggested that AO-I protected mice acute lung injury induced by LPS
      via inhibition of TLR4 expression and NF-kappaB activation. 

PMID- 26297301
TI  - Toll-like receptor signaling in hematopoietic homeostasis and the pathogenesis of
      hematologic diseases.
AB  - Toll-like receptors (TLRs), which are found in innate immune cells, are essential
      mediators of rapid inflammatory responses and appropriate T-cell activation in
      response to infection and tissue damage. Accumulating evidence suggests that TLR
      signaling is involved in normal hematopoiesis and specific hematologic
      pathologies. Particular TLRs and their downstream signaling mediators are
      expressed not only in terminally differentiated innate immune cells but also in
      early hematopoietic progenitors. Sterile activation of TLR signaling is required
      to generate early embryonic hematopoietic progenitor cells. In adult animals, TLR
      signaling directly or indirectly promotes differentiation of myeloid cells at the
      expense of that of lymphoid cells and the self-renewal of hematopoietic stem
      cells during infection and tissue damage. Activating mutations of the MyD88 gene,
      which codes for a key adaptor involved in TLR signaling, are commonly detected in
      B-cell lymphomas and other B-cell hematopathologies. Dysregulated TLR signaling
      contributes to the pathogenesis of many hematopoietic disorders, including bone
      marrow failure, myelodysplastic syndrome, and acute myeloid leukemia. Complete
      elucidation of the molecular mechanisms by which TLR signaling mediates the
      regulation of both normal and pathogenic hematopoiesis will prove valuable to the
      development of targeted therapies and strategies for improved treatment of
      hematopoietic disorders. 

PMID- 26297304
TI  - Tumor suppression effects of myoepithelial cells on mice breast cancer.
AB  - Several studies have assumed that myoepithelial cells (MECs) loss may contribute
      to epithelial tumor induction and/or progression. We adopted an in vitro assay
      and a syngeneic mice breast cancer model with histological and molecular
      characteristics resembling human lesions to evaluate tumor suppression effects of
      MECs. Flow cytometric, cell viability, blood chemistry, transmission electron
      microscope, immunohistochemistry and qRT-PCR assays were performed at the end of
      the study. We demonstrated that MECs could significantly suppress the viability
      of cancer cells at different time points (P<0.05). At the end of the fourth and
      fifth weeks, treated mice had smaller tumor volume compared with control animals.
      Average tumor volume was significantly less in treated groups than control group
      at days 21 (0.38+/-0.19 vs. 1.99+/-0.13 cm3), 28 (0.57+/-0.3 vs. 2.5+/-0.37 cm3)
      and 35 (0.7+/-0.35 vs. 2.65+/-0.4 cm3) after tumor cell injection (P<0.05). No
      hematological, hepatocellular, and renal toxicities were seen in MECs treated
      groups. Ultrastructural features revealed severe relationship between adjacent
      tumoral cells and loose interconnections of neoplastic cells in treated group.
      Immunohistochemical examinations of breast tumors showed high p63 and low alpha
      smooth muscle actin protein expression in treated mice compared to control
      (P<0.05). MRNA expressions of TNF-alpha, smooth muscle-myosin heavy chain,
      connexin 43, and maspin were significantly up-regulated in breast tumor tissues
      in treated group compared to control (P<0.05). VEGF and alpha-smooth muscle actin
      mRNA expression were reduced in treated animals (P<0.05). The present study
      highlighted the potential tumor suppression effects of MECs on breast cancer in a
      typical animal model.

PMID- 26297305
TI  - Mechanisms of vasorelaxation induced by the cannabidiol analogue compound O-1602
      in the rat small mesenteric artery.
AB  - Atypical cannabinoid O-1602 (5-Methyl-4-[(1R,6R)-3-methyl-6-(1-cyclohexen-1-yl]
      1,3-benzenediol) induces vasorelaxation and activates the orphan G protein
      coupled receptor GPR55 in human endothelial cells. This study investigates the
      underlying mechanisms of vasorelaxation induced by this compound. The vasodilator
      activity was assessed in the rat third order branch of the superior mesenteric
      artery using a wire myograph. The vasorelaxation was partially endothelium
      dependent (pEC50%=5.8+/-0.3). The endothelial component was antagonized by the
      putative endothelial receptor antagonists rimonabant (3 uM; pEC50%=5.1+/-0.2) and
      O-1918 (10 uM; pEC50%=5.3+/-0.2) but not by the CB1 and CB2 receptors antagonists
      AM 251 (10 uM) and AM 630 (10 uM), respectively. The vasorelaxation was not
      pertussis toxin-sensitive and not mediated through TRPVI receptors or by the
      release of NO, but was reduced by inhibition of Ca2+ sensitive K+ channels (KCa).
      In endothelium-denuded vessels, O-1602 abolished CaCl2-induced contraction and
      the inhibition was apparently reversed by O-1918. O-1602 mediates its
      vasorelaxant effects partly by an endothelium-dependent pathway involving
      rimonabant- and O-1918-sensitive targets that are distinct from the classical CB1
      and CB2 cannabinoid receptors and might involve activation of KCa. The
      endothelium-independent relaxation might involve interfering with Ca2+ entry.

PMID- 26297306
TI  - Enzyme stability, thermodynamics and secondary structures of alpha-amylase as
      probed by the CD spectroscopy.
AB  - An amylase of a thermophilic bacterium, Bacillus sp. TSSC-3 (GenBank Number,
      EU710557) isolated from the Tulsi Shyam hot spring reservoir (Gujarat, India) was
      purified to the homogeneity in a single step on phenyl sepharose 6FF. The
      molecular weight of the enzyme was 25kD, while the temperature and pH optima for
      the enzyme catalysis were 80 degrees C and 7, respectively. The purified enzyme
      was highly thermostable with broad pH stability and displayed remarkable
      resistance against surfactants, chelators, urea, guanidine HCl and various
      solvents as well. The stability and changes in the secondary structure of the
      enzyme under various extreme conditions were determined by the circular dichroism
      (CD) spectroscopy. The stability trends and the changes in the alpha-helices and
      beta-sheets were analyzed by Mean Residual Ellipticity (MRE) and K2D3. The CD
      data confirmed the structural stability of the enzyme under various harsh
      conditions, yet it indicated reduced alpha-helix content and increased beta
      sheets upon denaturation. The thermodynamic parameters; deactivation rate
      constant, half-life, changes in entropy, enthalpy, activation energy and Gibb's
      free energy indicated that the enzyme-substrate reactions were highly stable. The
      overall profile of the enzyme: high thermostability, alkalitolerance, calcium
      independent nature, dextrose equivalent values and resistance against chemical
      denaturants, solvents and surfactants suggest its commercial applications. 

PMID- 26297307
TI  - Time-dependent viscometry study of endoglucanase action on xyloglucan: A real
      time approach.
AB  - Hydrolysis of xyloglucan from Tamarindus indica and Hymenaea courbaril seeds with
      endoglucanase (EGII), which randomly breaks the (1->4)-linked beta-glycosidic
      bonds of the polymer chain, was monitored in real time using time-dependent
      viscometry analysis (TDV). For both samples there was a decrease in the intrinsic
      viscosity ([eta]), viscosity average molar mass (Mv), radius de gyration (Rg) and
      persistence length (Lp) immediately after the addition of the enzyme. It was
      observed the formation of oligosaccharides and oligomers composed of ~2 units, up
      to 140min. Galactose-containing side chains two positions away from the non
      substituted glucose, modulated the action of EGII, and the complete hydrolysis of
      the XG oligomers occurred after 24h. The results demonstrate for the first time
      the real-time degradation of xyloglucan as well the macromolecular and
      oligosaccharide composition during the EGII hydrolysis process. 

PMID- 26297308
TI  - Characteristics Analyses and Comparisons of the Protein Structure Networks
      Constructed by Different Methods.
AB  - Protein structure networks (PSNs) were widely used in analyses of protein
      structure and function. In this work, we analyzed and compared the characters of
      PSNs by different methods. The degrees of the different types of the nodes were
      found to be associated with the amino acid characters, including SAS, secondary
      structure, hydropathy and the volume of amino acids. It showed that PSNs by the
      methods of CA10, SC10 and AT5 inherited more amino acid characters and had higher
      correlations with the original protein structures. And PSNs by these three
      methods would be powerful tools in understanding the characters of protein
      structures. 

PMID- 26297309
TI  - Targeting Heat Shock Proteins 60 and 70 of Toxoplasma gondii as a Potential Drug
      Target: In Silico Approach.
AB  - Heat shock proteins (Hsps) 60 and 70 are postulated as a potential drug target
      for toxoplasmosis due to its importance in the developmental and survival of
      Toxoplasma gondii (T. gondii). As of today, there have been no reports on three
      dimensional (3D) structure of Hsp60 and Hsp70 deposited in the Brookhaven Protein
      Data Bank. Hence, this study was conducted to predict 3D structures for Hsp60 and
      Hsp70 in T. gondii by homology modeling. Selection of the best predicted model
      was done based on multiple scoring functions. In addition, virtual screening was
      performed to short-list chemical compounds from the National Cancer Institute
      (NCI) Diversity Set III in search of potential inhibitor against Hsp60 and Hsp70
      in T. gondii. Prior to virtual screening, binding sites of Hsp60 and Hsp70 were
      predicted using various servers and were used as the center in docking studies.
      The Hsps were docked against known natural ligands to validate the method used in
      estimating free energy of binding (FEB) and possible interactions between ligand
      and protein. Virtual screening was performed with a total of 1560 compounds from
      the NCI Diversity Set III. The compounds were ranked subsequently according to
      their FEB. Molecular basis of interactions of the top five ranked compounds was
      investigated using Ligplot+. The major interactions exhibited were hydrogen
      bonding and hydrophobic interactions in binding to Hsp60 and Hsp70. The results
      obtained provided information and guidelines for the development of inhibitors
      for Hsp60 and Hsp70 in T. gondii.

PMID- 26297310
TI  - TPMT Polymorphism: When Shield Becomes Weakness.
AB  - Thiopurine methyltransferase (TPMT) is a cytoplasmic transmethylase present in
      both prokaryotes and eukaryotes. In humans, it shows its presence in almost all
      of the tissues, predominantly in liver and kidney. TPMT is one of the important
      metabolic enzymes of phase II metabolic pathway and catalyzes methylation of
      thiopurine drugs such as azathioprine, 6-thioguanine and 6-mercaptopurine, which
      are used to treat patients with neoplasia and autoimmune disease as well as
      transplant recipients. In this sense, TPMT acts as shield against toxic effect of
      these drugs. Pharmacogenomic studies revealed that genetic polymorphism in TPMT
      is responsible for variable and, in some cases, adverse drug reaction. Those
      human groups who carry variants of TPMT (i.e., [Formula: see text], [Formula: see
      text], [Formula: see text]) are at high risk, because they are unable to
      metabolize thiopurine drugs thus becoming a weakness of patients against these
      drugs. Keeping in the mind the importance of TPMT, this review discusses the
      existence and distribution of various TPMT variants throughout different ethnic
      groups and risk of adverse drug reactions to them, and how they can avoid this
      risk of side effects. The review also highlighted factors responsible for
      variable reactions of TPMT, how this TPMT polymorphism can be considered in drug
      designing process to avoid toxic effects, designing precautions against them and
      more importantly designing personalized medicine. 

PMID- 26297311
TI  - Identification of Dual Natural Inhibitors for Chronic Myeloid Leukemia by Virtual
      Screening, Molecular Dynamics Simulation and ADMET Analysis.
AB  - Chronic myeloid leukemia (CML) is a disease of bone marrow stem cells caused by
      excessive growth and accumulation of granulocytes in the blood. Aberrant
      expression of the BCR-ABL proteins in bone marrow stem cells have found out in 95
      % cases of CML. Tyrosine Kinase domains (SH2 and SH3) of BCR-ABL proteins are the
      potent targets to inhibit the process. Initially, imatinib is preferred as an
      efficient inhibitor to control functional activity of disease. Recently, it has
      been reported that the advanced stage of CML developed resistance against
      imatinib. In continuation, dasatinib is the first drug to combat against this
      disease by targeting multiple receptors and proven better as compared to
      imatinib. Here, an attempt has been made to identify similar analogs of
      dasatinib. Virtual screening was performed against various natural compound
      databases to get some potent natural compounds which are able to inhibit more
      than one receptor. Binding affinity of screened natural compounds was compared
      with some of the well-known inhibitors like imatinib, dasatinib, nilotinib etc.,
      by analyzing their docking score and binding efficiency with the receptor.
      Stability of the best ligand-receptor complex was checked by performing 10 ns
      molecular dynamics simulation. ADMET properties of the obtained screened
      compounds were analyzed to check drug like property. Based on the aforementioned
      analysis, it has been suggested that these screened potent compounds are capable
      to inhibit multiple receptor proteins like ABL and SRC and consequently combat
      against the deadly disease CML. 

PMID- 26297312
TI  - Insights from the Molecular Docking of Hydrolytic Products of Methyl Isocyanate
      (MIC) to Inhibition of Human Immune Proteins.
AB  - This study is an attempt to find the reason for immunological suppression in
      victims of Bhopal gas tragedy during 1984 against Mycobacterium tuberculosis
      (Mtb) infection. Here, we tried to understand this problem by studying
      interactions between immune proteins associated with susceptibility to
      tuberculosis and hydrolytic products of methyl isocyanate (MIC) released during
      the tragedy. The hydrolytic products of MIC i.e. dimethyl urea, trimethyl urea
      and trimethyl isocyanurate were docked to different human immune proteins against
      Mtb using AutoDock 4.0. Results shows that all hydrolytic products (dimethyl
      urea, trimethyl urea and trimethylisocyanurate) strongly inhibit to CD40 ligand,
      and their binding energies were found to be [Formula: see text] G [Formula: see
      text]3.51, [Formula: see text]3.79, [Formula: see text]4.55 (Kcal/mole),
      respectively. Further, to check the stability of docked complex, we performed the
      molecular dynamics simulation study which also shows that CD40 Ligand was
      maximally inhibited by trimethylisocyanurate and has a role in the macrophage
      activation for the destruction of M. tuberculosis. The present study may lead to
      better understanding of human immune protein inhibition by hydrolytic product of
      MIC. 

PMID- 26297313
TI  - Frey procedure for chronic pancreatitis in children: A single center experience.
AB  - BACKGROUND: There is paucity of literature regarding the Frey procedure for
      children with chronic pancreatitis. The purpose of this study is to present our
      experience with the Frey procedure in children. METHODS: This is an observational
      retrospective review study. All children, who underwent a Frey procedure between
      August 2007 and May 2014 in the Department of Surgical Gastroenterology,
      Institute of Postgraduate Medical Education and Research, Kolkata, India were
      included in this study. RESULTS: Twenty four children were included in our study.
      There were 13 girls and 11 boys. Mean age at operation was 13.95years (range, 4
      to 18years). Mean duration between the diagnosis of chronic pancreatitis and
      surgery was 4.41years (range, 1 to 14years). Frey procedure was performed after
      failure of medical or endoscopic therapy. Mean duration of operation and blood
      loss were 215minutes (range, 150-300minutes) and 177ml (range, 50 to 500ml)
      respectively. Average postoperative hospital stay was 8days (range, 5 to 16days).
      Five patients (21%) developed postoperative complications. There was no in
      hospital mortality and no patient required reoperation for postoperative
      complications. More than a median follow-up of 29months (range, 3-78months), 91%
      of the patients remained pain free. CONCLUSION: Frey procedure is safe and
      feasible in children with acceptable perioperative complications and good short
      term pain control.

PMID- 26297314
TI  - Exploring the influence of context in a community-based facilitation intervention
      focusing on neonatal health and survival in Vietnam: a qualitative study.
AB  - BACKGROUND: In the Neonatal health - Knowledge into Practice (NeoKIP) trial in
      Vietnam, local stakeholder groups, supported by trained laywomen acting as
      facilitators, promoted knowledge translation (KT) resulting in decreased neonatal
      mortality. In general, as well as in the community-based NeoKIP trial, there is a
      need to further understand how context influences KT interventions in low- and
      middle-income countries (LMICs). Thus, the objective of this study was to explore
      the influence of context on the facilitation process in the NeoKIP intervention.
      METHODS: A secondary content analysis was performed on 16 Focus Group Discussions
      with facilitators and participants of the stakeholder groups, applying an
      inductive approach to the content on context through naive understanding and
      structured analysis. RESULTS: The three main-categories of context found to
      influence the facilitation process in the NeoKIP intervention were: (1) Support
      and collaboration of local authorities and other communal stakeholders; (2)
      Incentives to, and motivation of, participants; and (3) Low health care coverage
      and utilization. In particular, the role of local authorities in a KT
      intervention was recognized as important. Also, while project participants
      expected financial incentives, non-financial benefits such as individual learning
      were considered to balance the lack of reimbursement in the NeoKIP intervention.
      Further, project participants recognized the need to acknowledge the needs of
      disadvantaged groups. CONCLUSIONS: This study provides insight for further
      understanding of the influence of contextual aspects to improve effects of a KT
      intervention in Vietnam. We suggest that future KT interventions should apply
      strategies to improve local authorities' engagement, to identify and communicate
      non-financial incentives, and to make disadvantaged groups a priority. Further
      studies to evaluate the contextual aspects in KT interventions in LMICs are also
      needed.

PMID- 26297315
TI  - The specificity of long noncoding RNA expression.
AB  - Over the last decade, long noncoding RNAs (lncRNAs) have emerged as a fundamental
      molecular class whose members play pivotal roles in the regulation of the genome.
      The observation of pervasive transcription of mammalian genomes in the early
      2000s sparked a revolution in the understanding of information flow in eukaryotic
      cells and the incredible flexibility and dynamic nature of the transcriptome. As
      a molecular class, distinct loci yielding lncRNAs are set to outnumber those
      yielding mRNAs. However, like many important discoveries, the road leading to
      uncovering this diverse class of molecules that act through a remarkable
      repertoire of mechanisms, was not a straight one. The same characteristic that
      most distinguishes lncRNAs from mRNAs, i.e. their developmental-stage, tissue-,
      and cell-specific expression, was one of the major impediments to their discovery
      and recognition as potentially functional regulatory molecules. With growing
      numbers of lncRNAs being assigned to biological functions, the specificity of
      lncRNA expression is now increasingly recognized as a characteristic that imbues
      lncRNAs with great potential as biomarkers and for the development of highly
      targeted therapeutics. Here we review the history of lncRNA research and how
      technological advances and insight into biological complexity have gone hand-in
      hand in shaping this revolution. We anticipate that as increasing numbers of
      these molecules, often described as the dark matter of the genome, are
      characterized and the structure-function relationship of lncRNAs becomes better
      understood, it may ultimately be feasible to decipher what these non-(protein)
      coding genes encode. This article is part of a Special Issue entitled: Clues to
      long noncoding RNA taxonomy1, edited by Dr. Tetsuro Hirose and Dr. Shinichi
      Nakagawa. 

PMID- 26297316
TI  - Modeling contact tracing in outbreaks with application to Ebola.
AB  - Contact tracing is an important control strategy for containing Ebola epidemics.
      From a modeling perspective, explicitly incorporating contact tracing with
      disease dynamics presents challenges, and population level effects of contact
      tracing are difficult to determine. In this work, we formulate and analyze a
      mechanistic SEIR type outbreak model which considers the key features of contact
      tracing, and we characterize the impact of contact tracing on the effective
      reproduction number, Re, of Ebola. In particular, we determine how relevant
      epidemiological properties such as incubation period, infectious period and case
      reporting, along with varying monitoring protocols, affect the efficacy of
      contact tracing. In the special cases of either perfect monitoring of traced
      cases or perfect reporting of all cases, we derive simple formulae for the
      critical proportion of contacts that need to be traced in order to bring the
      effective reproduction number Re below one. Also, in either case, we show that Re
      can be expressed completely in terms of observable reported case/tracing
      quantities, namely Re = k((1-q)/q)+km where k is the number of secondary traced
      infected contacts per primary untraced reported case, km is the number of
      secondary traced infected contacts per primary traced reported case and (1-q)/q
      is the odds that a reported case is not a traced contact. These formulae quantify
      contact tracing as both an intervention strategy that impacts disease spread and
      a probe into the current epidemic status at the population level. Data from the
      West Africa Ebola outbreak is utilized to form real-time estimates of Re, and
      inform our projections of the impact of contact tracing, and other control
      measures, on the epidemic trajectory.

PMID- 26297317
TI  - Peripheral neuron plasticity is enhanced by brief electrical stimulation and
      overrides attenuated regrowth in experimental diabetes.
AB  - Peripheral nerve regrowth is less robust than commonly assumed, particularly when
      it accompanies common clinical scenarios such as diabetes mellitus. Brief
      extracellular electrical stimulation (ES) facilitates the regeneration of
      peripheral nerves in part through early activation of the conditioning injury
      response and BDNF. Here, we explored intrinsic neuronal responses to ES to
      identify whether ES might impact experimental diabetes, where regeneration is
      attenuated. ES altered several regeneration related molecules including rises in
      tubulin, Shh (Sonic hedgehog) and GAP43 mRNAs. ES was associated with rises in
      neuronal intracellular calcium but its strict linkage to regrowth was not
      confirmed. In contrast, we identified PI3K-PTEN involvement, an association
      previously linked to diabetic regenerative impairment. Following ES there were
      declines in PTEN protein and mRNA both in vitro and in vivo and a PI3K inhibitor
      blocked its action. In vitro, isolated diabetic neurons were capable of mounting
      robust responsiveness to ES. In vivo, ES improved electrophysiological and
      behavioral indices of nerve regrowth in a chronic diabetic model of mice with pre
      existing neuropathy. Regrowth of myelinated axons and reinnervation of the
      epidermis were greater following ES than sham stimulation. Taken together, these
      findings identify a role for ES in supporting regeneration during the challenges
      of diabetes mellitus. 

PMID- 26297318
TI  - A systematic immunoprecipitation approach reinforces the concept of common
      conformational alterations in amyotrophic lateral sclerosis-linked SOD1 mutants.
AB  - Mutations in the Cu, Zn superoxide dismutase (SOD1) gene are one of the causative
      agents of amyotrophic lateral sclerosis (ALS). Although more than 100 different
      mutations in SOD1 have been identified, it is unclear whether all the mutations
      are pathogenic or just single nucleotide polymorphisms (SNPs) unrelated to the
      disease. Our previous systematic analysis found that all pathogenic SOD1 mutants
      (SOD1(mut)) have a common property, namely, an association with Derlin-1, a
      component of the endoplasmic reticulum-associated degradation machinery. For the
      proposed mechanism, we found that most pathogenic SOD1(mut) have a constitutively
      exposed Derlin-1-binding region (DBR), which is concealed in wild-type SOD1
      (SOD1(WT)). Moreover, we generated MS785, a monoclonal antibody against DBR.
      MS785 distinguished most ALS-causative SOD1(mut) from both SOD1(WT) and non-toxic
      SOD1(mut). However, MS785 could not recognize SOD1(mut) that has mutations in the
      MS785 epitope region. Here, we developed a new diagnostic antibody, which could
      compensate for this shortcoming of MS785. We hypothesized that in ALS-causative
      SOD1(mut), the DBR-neighboring region [SOD1(30-40)] may also be exposed. We then
      generated MS27, a monoclonal antibody against SOD1(30-40). We found that MS27
      could distinguish SOD1(WT) from the pathogenic SOD1(mut), which has mutations in
      the MS785 epitope region. Moreover, all pathogenic SOD1(mut), without exception,
      were immunoprecipitated with a combination of MS785 and MS27. The MS785-MS27
      combination could be developed as a novel mechanism-based biomarker for the
      diagnosis of ALS. 

PMID- 26297319
TI  - Increased central microglial activation associated with peripheral cytokine
      levels in premanifest Huntington's disease gene carriers.
AB  - Previous studies have shown activation of the immune system and altered immune
      response in Huntington's disease (HD) gene carriers. Here, we hypothesized that
      peripheral and central immune responses could be concurrent pathophysiological
      events and represent a global innate immune response to the toxic effects of
      mutant huntingtin in HD gene carriers. We sought to investigate our hypothesis
      using [(11)C]PK11195 PET as a translocator protein (TSPO) marker of central
      microglial activation, together with assessment of peripheral plasma cytokine
      levels in a cohort of premanifest HD gene carriers who were more than a decade
      from predicted symptomatic conversion. Data were also compared to those from a
      group of healthy controls matched for age and gender. We found significantly
      increased peripheral plasma IL-1beta levels in premanifest HD gene carriers
      compared to the group of normal controls (P=0.018). Premanifest HD gene carriers
      had increased TSPO levels in cortical, basal ganglia and thalamic brain regions
      (P<0.001). Increased microglial activation in somatosensory cortex correlated
      with higher plasma levels of IL-1beta (rs=0.87, P=0.013), IL-6 (rs=0.85,
      P=0.013), IL-8 (rs=0.68, P=0.045) and TNF-alpha (rs=0.79; P=0.013). Our findings
      provide first in vivo evidence for an association between peripheral and central
      immune responses in premanifest HD gene carriers, and provide further supporting
      evidence for the role of immune dysfunction in the pathogenesis of HD. 

PMID- 26297320
TI  - Fatigue in Egyptian patients with rheumatic diseases: a qualitative study.
AB  - OBJECTIVES: Fatigue is frequent in rheumatic diseases. Fatigue expression and
      consequences may be modified by cultural differences. Our objective was to
      increase the understanding of the fatigue experience and characteristics among
      Egyptian, Muslim patients with rheumatic diseases. METHODS: Prospective
      monocentric qualitative study based on conventional qualitative content analysis,
      inductive reasoning, grounded theory. Egyptian patients with rheumatoid arthritis
      (RA), fibromyalgia or axial spondyloarthritis (AxSpA) were asked about fatigue,
      its patterns, consequences and self-management. RESULTS: Of the 60 patients
      interviewed, 20 patients had each disease (RA, fibromyalgia and AxSpA); median
      ages ranged from 34 to 40 years. Patients were mainly male (N = 40, 66%), had 3
      to 7 years (mean) of disease duration and had moderate disease activity. Some
      aspects of the patients' experience of fatigue may be specific to the Egyptian
      and Muslim culture such as the description of fatigue as a physical more than a
      mental impact of the disease, the response to the effect of fatigue on sexual
      function and the gender specific (women more than men) limitation of social
      activities due to fatigue which was more obvious in our study than other previous
      studies. Other aspects of patients' experience of fatigue like overlap between
      the patients' perception of fatigue and pain and coping strategies were similar
      to the findings in previous studies. CONCLUSION: This study gives insights
      regarding fatigue in rheumatic diseases in an Arabic and Muslim culture.
      Similarities and differences with previous studies were noted and should be taken
      into account when assessing these patients.

PMID- 26297321
TI  - SBIRT Implementation for Adolescents in Urban Federally Qualified Health Centers.
AB  - BACKGROUND: Alcohol, tobacco, and other drug use remains highly prevalent among
      US adolescents and is a threat to their well-being and to the public health.
      Evidence from clinical trials and meta-analyses supports the effectiveness of
      Screening, Brief Intervention and Referral to Treatment (SBIRT) for adolescents
      with substance misuse but primary care providers have been slow to adopt this
      evidence-based approach. The purpose of this paper is to describe the
      theoretically informed methodology of an on-going implementation study. METHODS:
      This study protocol is a multi-site, cluster randomized trial (N=7) guided by
      Proctor's conceptual model of implementation research and comparing two principal
      approaches to SBIRT delivery within adolescent medicine: Generalist vs.
      Specialist. In the Generalist Approach, the primary care provider delivers brief
      intervention (BI) for substance misuse. In the Specialist Approach, BIs are
      delivered by behavioral health counselors. The study will also examine the
      effectiveness of integrating HIV risk screening within an SBIRT model.
      Implementation Strategies employed include: integrated team development of the
      service delivery model, modifications to the electronic medical record, regular
      performance feedback and supervision. Implementation outcomes, include:
      Acceptability, Appropriateness, Adoption, Feasibility, Fidelity, Costs/Cost
      Effectiveness, Penetration, and Sustainability. DISCUSSION: The study will fill a
      major gap in scientific knowledge regarding the best SBIRT implementation
      strategy at a time when SBIRT is poised to be brought to scale under health care
      reform. It will also provide novel data to inform the expansion of the SBIRT
      model to address HIV risk behaviors among adolescents. Finally, the study will
      generate important cost data that offer guidance to policymakers and clinic
      directors about the adoption of SBIRT in adolescent health care.

PMID- 26297322
TI  - Local Implementation of Alcohol Screening and Brief Intervention at Five Veterans
      Health Administration Primary Care Clinics: Perspectives of Clinical and
      Administrative Staff.
AB  - BACKGROUND AND OBJECTIVE: Population-based alcohol screening, followed by brief
      intervention for patients who screen positive for unhealthy alcohol use, is
      widely recommended for primary care settings and considered a top prevention
      priority, but is challenging to implement. However, new policy initiatives in the
      U.S., including the Affordable Care Act, may help launch widespread
      implementation. While the nationwide Veterans Health Administration (VA) has
      achieved high rates of documented alcohol screening and brief intervention,
      research has identified quality problems with both. We conducted a qualitative
      key informant study to describe local implementation of alcohol screening and
      brief intervention from the perspectives of frontline adopters in VA primary care
      in order to understand the process of implementation and factors underlying
      quality problems. METHODS: A purposive snowball sampling method was used to
      identify and recruit key informants from 5 VA primary care clinics in the
      northwestern U.S. Key informants completed 20-30 minute semi-structured
      interviews, which were recorded, transcribed, and qualitatively analyzed using
      template analysis. RESULTS: Key informants (N=32) included: clinical staff
      (n=14), providers (n=14), and administrative informants (n=4) with varying
      participation in implementation of and responsibility for alcohol screening and
      brief intervention at the medical center. Ten inter-related themes (5 a priori
      and 5 emergent) were identified and grouped into 3 applicable domains of
      Greenhalgh's conceptual framework for dissemination of innovations, including
      values of adopters (theme 1), processes of implementation (themes 2 and 3), and
      post-implementation consequences in care processes (themes 4-10). While key
      informants believed alcohol use was relevant to health and important to address,
      the process of implementation (in which no training was provided and electronic
      clinical reminders "just showed up") did not address critical training and
      infrastructure needs. Key informants lacked understanding of the goals of
      screening and brief intervention, believed referral to specialty addictions
      treatment (as opposed to offering brief intervention) was the only option for
      following up on a positive screen, reported concern regarding limited
      availability of treatment resources, and lacked optimism regarding patients'
      interest in seeking help. CONCLUSIONS: Findings suggest that the local process of
      implementing alcohol screening and brief intervention may have inadequately
      addressed important adopter needs and thus may have ultimately undermined,
      instead of capitalized on, staff and providers' belief in the importance of
      addressing alcohol use as part of primary care. Additional implementation
      strategies, such as training or academic detailing, may address some unmet needs
      and help improve the quality of both screening and brief intervention. However,
      these strategies may be resource-intensive and insufficient for comprehensively
      addressing implementation barriers.

PMID- 26297323
TI  - Real-Time Readiness to Quit and Peer Smoking within a Text Message Intervention
      for Adolescent Smokers: Modeling Mechanisms of Change.
AB  - The psychological construct, readiness to change, is established as a central
      construct within behavioral change theories such as motivational interviewing
      (MI). Less is known about the interplay of mechanisms for change within
      adolescent treatment populations. Understanding the timing and interactive
      influence that adolescents' readiness to stop smoking and peer smoking have on
      subsequent tobacco use is important to advance intervention research. Toward this
      end, we used ecological momentary assessment (EMA) data from an automated texting
      smoking intervention randomized controlled trial to model the interactive effects
      of readiness to stop smoking and friends smoking on adolescent tobacco use. Two
      hundred adolescents were randomized into experimental treatment or attention
      control conditions, provided smart phones, and were followed for 6 months.
      African American youth represented the majority of the sample. We collected
      monthly EMA data for 6 months on friends smoking and readiness to stop smoking as
      well as survey outcome data. We tested a moderated mediation model using bias
      corrected bootstrapping to determine if the indirect effect of treatment on
      cigarettes smoked through readiness to stop smoking was moderated by friends
      smoking. Findings revealed that readiness to stop smoking mediated the effects of
      treatment on cigarettes smoked for those adolescents with fewer friends smoking,
      but not for those with more friends smoking. These results support importance of
      peer-focused interventions with urban adolescents and provide target mechanisms
      for future research.

PMID- 26297324
TI  - Heavy-Drinking Smokers' Treatment Needs and Preferences: A Mixed-Methods Study.
AB  - The purpose of this mixed methods study was to describe the smoking and
      psychological characteristics of heavy-drinking smokers, their perceptions of
      smoking and drinking, and their smoking and alcohol treatment preferences to
      inform an integrated smoking and alcohol intervention. Heavy-drinking smokers
      (N=26) completed standardized surveys and participated in semi-structured focus
      group interviews. Participants reported a strong association between their
      smoking and drinking. Participants were more motivated to quit smoking than to
      reduce their drinking but perceived greater barriers to smoking cessation.
      Stress/negative affect was closely linked with both behaviors. They expressed
      overall enthusiasm for a smoking and alcohol intervention but had specific format
      and content preferences. Half preferred an integrated treatment format whereas
      others preferred a sequential treatment model. The most preferred content
      included personalized health feedback and a way to monitor health gains after
      behavior changes. 

PMID- 26297325
TI  - Effects of pre-exercise alkalosis on the decrease in VO2 at the end of all-out
      exercise.
AB  - PURPOSE: This study determined the effects of pre-exercise sodium bicarbonate
      ingestion (ALK) on changes in oxygen uptake (VO2) at the end of a supramaximal
      exercise test (SXT). METHODS: Eleven well-trained cyclists completed a 70-s all
      out cycling effort, in double-blind trials, after oral ingestion of either 0.3 g
      kg(-1) of sodium bicarbonate (NaHCO3) or 0.2 g kg(-1) body mass of calcium
      carbonate (PLA). Blood samples were taken to assess changes in acid-base balance
      before the start of the supramaximal exercise, and 0, 5 and 8 min after the
      exercise; ventilatory parameters were also measured at rest and during the SXT.
      RESULTS: At the end of the PLA trial, which induced mild acidosis (blood pH =
      7.20), subjects presented a significant decrease in VO2 (P < 0.05), which was
      related to the amplitude of the decrease in minute ventilation (VE) during the
      SXT (r = 0.70, P < 0.01, n = 11). Pre-exercise metabolic alkalosis significantly
      prevented the exercise-induced decrease in VO2 in eleven well-trained
      participants (PLA:12.5 +/- 2.1 % and ALK: 4.9 +/- 0.9 %, P < 0.05) and the
      decrease in mean power output was significantly less pronounced in ALK (P <
      0.05). Changes in the VO2 decrease between PLA and ALK trials were positively
      related to changes in the VE decrease (r = 0.74, P < 0.001), but not to changes
      in power output (P > 0.05). CONCLUSIONS: Pre-exercise alkalosis counteracted the
      VO2 decrease related to mild acidosis, potentially as a result of changes in VE
      and in muscle acid-base status during the all-out supramaximal exercise.

PMID- 26297327
TI  - Identification of bacteria from aerobic and anaerobic blood cultures after short
      cultivation by matrix-assisted laser desorption/ionization-time-of-flight mass
      spectrometry.

PMID- 26297328
TI  - Hepatitis C virus post-exposure prophylaxis: A reasonable option in the era of
      pangenotypic direct-acting antivirals?

PMID- 26297326
TI  - Interference with acute nausea and anticipatory nausea in rats by fatty acid
      amide hydrolase (FAAH) inhibition through a PPARalpha and CB1 receptor mechanism,
      respectively: a double dissociation.
AB  - RATIONALE: Fatty acid amide hydrolase (FAAH) inhibition elevates anandamide
      (AEA), which acts on cannabinoid (CB1 and CB2) receptors, as well as N
      palmitoylethanolamide (PEA) and N-oleoylethanolamine (OEA), which act on
      peroxisome proliferator-activated receptor alpha (PPARalpha). Here, we determine
      the mechanism of action of FAAH inhibition on acute and anticipatory nausea (AN).
      OBJECTIVE: We compared the effectiveness and mechanism of action of two FAAH
      inhibitors, URB597 and PF-3845, to reduce acute nausea and AN in rodent models of
      conditioned gaping. MATERIALS AND METHODS: For assessment of acute nausea, rats
      were pretreated with vehicle (VEH), URB597 (0.3 and 10 mg/kg, experiment 1a) or
      PF-3845 (10 mg/kg, experiment 1b) 120 min prior to a saccharin-lithium chloride
      (LiCl) pairing. To assess the CB1 receptor or PPARalpha mediation of the effect
      of PF-3845 on acute nausea, rats were also pretreated with rimonabant or MK886,
      respectively. For assessment of AN, following four pairings of a novel context
      with LiCl, rats received a pretreatment of VEH, URB597 (0.3 mg/kg, experiment
      2a), or PF-3845 (10, 20 mg/kg, experiment 2b) 120 min prior to placement in the
      AN context. To assess the CB1 receptor or PPARalpha mediation of the effect, rats
      were also pretreated with rimonabant or MK886, respectively. RESULTS: PF-3845 (10
      mg/kg, but not URB597 0.3 or 10 mg/kg) suppressed acute nausea via PPARalpha, but
      not CB1 receptors. URB597 (0.3 and 10 mg/kg) or PF-3845 (10 and 20 mg/kg) reduced
      AN via CB1 receptors, but not PPARalpha. CONCLUSIONS: FAAH inhibition reduces
      acute nausea and AN through PPARalpha and CB1 receptor mediated effects,
      respectively.

PMID- 26297329
TI  - Identification of glabridin as a bioactive compound in licorice (Glycyrrhiza
      glabra L.) extract that activates human peroxisome proliferator-activated
      receptor gamma (PPARgamma).
AB  - Licorice, the root and stolons of the Glycyrrhiza plant (Fabaceae), has been used
      for centuries as a food additive (sweetener), in cosmetics, and in traditional
      medicine. In this research, we provide evidence that licorice extract activates
      peroxisome proliferator-activated receptor gamma (PPARgamma) and, as identified
      through HPLC fractionation and mass spectroscopy, one of the activating
      phytochemicals is glabridin. Glabridin was shown to bind to and activate
      PPARgamma. It was also shown to activate PPARgamma-regulated gene expression in
      human hepatoma cells similar to known PPARgamma ligands and that the expression
      was blocked by a PPARgamma specific antagonist.

PMID- 26297330
TI  - Roseomonas oryzae sp. nov., isolated from paddy rhizosphere soil.
AB  - A non-motile, coccus-shaped, pale-pink-pigmented bacterium, designated strain
      JC288T, was isolated from a paddy rhizosphere soil collected from Western Ghats,
      Kankumbi, Karnataka, India. Cells were found to be Gram-stain-negative, and
      catalase- and oxidase-positive; the major fatty acids were C16 : 0, C16 :
      1omega7c/C16 : 1omega6c, C18 : 1omega7c/C18 : 1omega6c and C18 : 1 2-OH. The
      predominant respiratory quinone was Q-10 and the genomic DNA G+C content was 67.5
      mol%. Strain JC288T contained diphosphatidylglycerol, phosphatidylglycerol,
      phosphatidylethanolamine, phosphatidylcholine, four unidentified aminolipids,
      three unidentified phospholipids, two unidentified lipids, an aminophospholipid
      and a glycolipid. Hydroxyspirilloxanthin was the major carotenoid of strain
      JC288T. 16S rRNA gene sequence comparisons indicated that strain JC288T
      represents a member of the genus Roseomonas within the family Acetobacteraceae of
      the phylum Proteobacteria. Strain JC288T shared the highest 16S rRNA gene
      sequence similarity with Roseomonas rhizosphaerae YW11T (97.3 %), Roseomonas
      aestuarii JC17T (97.1 %), Roseomonas cervicalis CIP 104027T (95.9 %) and other
      members of the genus Roseomonas ( < 95.5 %). The distinct genomic difference and
      morphological, physiological and chemotaxonomic differences from the previously
      described taxa support the classification of strain JC288T as a representative of
      a novel species of the genus Roseomonas, for which the name Roseomonas oryzae sp.
      nov. is proposed. The type strain is JC288T ( = KCTC 42542T = LMG 28711T).

PMID- 26297331
TI  - The efficacy of ablation based on the combined use of the dominant frequency and
      complex fractionated atrial electrograms for non-paroxysmal atrial fibrillation.
AB  - BACKGROUND: This study aimed to evaluate an approach for an endpoint of non
      inducibility using a combined high-dominant frequency (DF) and continuous complex
      fractionated atrial electrogram (CFAE) ablation following circumferential
      pulmonary vein isolation (PVI) in a sequential fashion, including linear ablation
      as compared to PVI alone. METHODS AND RESULTS: A total of 84 non-paroxysmal
      patients with atrial fibrillation (AF) were investigated retrospectively. The AF
      patients were divided into two groups: patients with PVI following a combined
      high-DF and continuous CFAE ablation with linear ablation (substrate modification
      group, n=59) and those with PVI alone (n=25). DF sites of >=8Hz and then
      continuous CFAE sites defined by fractionation intervals of <=50ms were modified
      after PVI. The ablation endpoint was non-inducibility. Atrial tachyarrhythmias
      (ATs) could not be induced in 54 of 59 (92%) patients after a sequential
      ablation, and in 18 of 25 (64%) with PVI alone. The ATs freedom without
      antiarrhythmic drugs in the substrate modification group was significantly
      greater than that in those with PVI alone after 1 procedure during 12 months of
      follow-up (78.6% vs. 53.8%, log-rank test p=0.039). CONCLUSION: This sequential
      approach using a substrate based ablation was associated with a better clinical
      long-term outcome as compared to PVI alone.

PMID- 26297332
TI  - Antibiotic-associated diarrhea and the older dental patient: how do dentists
      respond?
AB  - BACKGROUND: Gastrointestinal complications from antibiotic use, including
      Clostridium difficile infection (CDI), can have significant morbidity, especially
      among older patients. This descriptive study surveyed dentists to find out how
      they would respond to a patient with signs indicating potential CDI. METHODS: A
      survey on prescribing medications for older patients was mailed to 1,000 dentists
      in New Jersey. Questions were asked regarding antibiotic selection, probiotic
      use, and approach to a patient scenario of diarrhea after antibiotic use.
      RESULTS: Respondents chose amoxicillin most frequently as an antibiotic, and
      clindamycin if penicillin allergy. When informed their patients had diarrhea,
      64.5% advised them to stop the antibiotic. If the patient continued to have
      diarrhea on follow-up, 75.5% contacted the patient's physician. Most (61.6%) do
      not prescribe probiotics prophylactically. CONCLUSIONS: Most dentists respond
      appropriately to antibiotic-associated diarrhea in advising to stop the
      antibiotic, and seeking physician involvement if no improvement, but there are
      still many who make recommendations that could delay appropriate care. Dentists
      may wish to learn more about benefits of probiotics.

PMID- 26297333
TI  - Red wine intake but not other alcoholic beverages increases total antioxidant
      capacity and improves pro-inflammatory profile after an oral fat diet in healthy
      volunteers.
AB  - INTRODUCTION: Different alcoholic beverages exert different effects on
      inflammation and oxidative stress but these results are controversial and scanty
      in some aspects. We analyze the effect of different alcoholic beverages after a
      fat-enriched diet on lipid profile, inflammatory factors and oxidative stress in
      healthy people in a controlled environment. METHODS: We have performed a cross
      over design in five different weeks. Sixteen healthy volunteers have received the
      same oral fat-enriched diet (1486kcal/m(2)) and a daily total amount of 16g/m(2)
      of alcohol, of different beverages (red wine, vodka, brandy or rum) and
      equivalent caloric intakes as sugar with water in the control group. We have
      measured the levels of serum lipids, high sensitivity C-reactive protein (hsCRP),
      tumor necrosis factor alpha (TNFalpha), interleukin 6 (IL-6), soluble
      phospholipase A2 (sPLA2), lipid peroxidation (LPO) and total antioxidant capacity
      (TAC). RESULTS: Red wine intake was associated with decreased of mean
      concentrations of hsCRP, TNFalpha and IL-6 induced by fat-enriched diet (p<0.05);
      nevertheless, sPLA2 concentrations were not significantly modified. After a fat
      enriched diet added with red wine, TAC increased as compared to the same diet
      supplemented with rum, brandy, vodka or the control (water with sugar) (p<0.05).
      CONCLUSIONS: Moderate red wine intake, but not other alcoholic beverages,
      decreased pro-inflammatory factors and increased total antioxidant capacity
      despite a fat-enriched diet intake in healthy young volunteers.

PMID- 26297334
TI  - Prevalence of and Risk Factors for Type 2 Diabetes Mellitus in Hyperlipidemia in
      China.
AB  - BACKGROUND: We explored the prevalence of and risk factors for type 2 diabetes in
      the adult population of Shanghai (China) with and without dyslipidemia. MATERIAL
      AND METHODS: We conducted a cross-sectional survey including 14 385 adults (aged
      16 to 88 years) in Shanghai using a stratified, multistage cluster sampling
      approach. RESULTS: Type 2 diabetes and hyperlipidemia were found in 1456 (10.1%)
      and 4583 (31.9%) subjects, respectively. Type 2 diabetes was more common in males
      (11.4%) than in females (9.2%, P<0.01), in the elderly (> or =65 years, 22.5%)
      than in younger (<55 years, <10%, P<0.01) individuals, and in urban (12.8%) than
      in rural populations (5.2%, P<0.01). Diabetes incidence was higher among patients
      with hyperlipidemia than in controls (16.9% vs. 7.0%, P<0.01; OR=2.72, 95% CI
      2.44-3.03). Compared with controls, the risk for diabetes in subjects with
      isolated hypertriglyceridemia, isolated hypercholesterolemia, and mixed
      hyperlipidemia increased 1.75-fold (95% CI 1.53-1.99), 1.53-fold (95% CI 1.17
      2.01), and 2.93-fold (95% CI 2.37-3.63), respectively. The fasting plasma glucose
      (FPG) and 2h-postprandial plasma glucose (2h-PG) increased with age in both
      sexes. The age- and sex-adjusted FPG and 2h-PG levels in hyperlipidemia were
      significantly higher than in controls (P<0.01). CONCLUSIONS: A high prevalence of
      type 2 diabetes in hyperlipidemia patients exists in Shanghai. Hyperlipidemia is
      associated with elevated blood glucose levels and therefore requires prompt
      intervention for prevention and treatment of diabetes in patients with
      dyslipidemia.

PMID- 26297335
TI  - Perceived stress status and sympathetic nervous system activation in young male
      patients with coronary artery disease in China.
AB  - BACKGROUND AND PURPOSE: Young Chinese male adults have faced increasing
      psychological stress. Whether this is associated with the increased risk of
      coronary artery disease (CAD) in young Chinese males remains unclear. This study
      aimed to evaluate the correlation and underlying mechanisms of perceived stress
      and CAD in young male patients. METHODS: A total of 178 male patients diagnosed
      as young CAD (aged <= 55 years) by coronary angiography (CAG) were enrolled, and
      181 age-matched non-CAD individuals were set as control group. Traditional
      cardiovascular risk factors and levels of epinephrine and norepinephrine were
      measured, and perceived stress status was accessed by Perceived Stress Scale
      (PSS). RESULTS: The PSS score was correlated with levels of epinephrine (r=0.45),
      norepinephrine (r=0.41), high-sensitivity C-reactive protein (hs-CRP) (r=0.38,
      p<0.01), and current smoking (r=0.32) (all p<0.05). Multivariate logistic
      regression analysis showed that smoking (OR, 3.12; 95%CI, 1.23-7.91),
      triglycerides (OR, 1.42; 95%CI, 1.04-1.94), hs-CRP (OR, 3.57; 95%CI, 1.65-7.72),
      and PSS score (OR, 1.81; 95%CI, 1.23-2.66) were independently correlated with CAD
      in young patients. The association between PSS score and risk of CAD become
      insignificant (OR, 1.43; 95%CI, 0.96-2.13) when further adjusted for the levels
      of epinephrine and norepinephrine. CONCLUSIONS: After adjustment for multiple
      cardiovascular risk factors, high perceived stress was an independent risk factor
      for CAD in young Chinese male patients. Abnormal activation of the sympathetic
      nervous system may play an important role linking perceived stress with the risk
      of CAD.

PMID- 26297336
TI  - Circadian aspects of myocardial infarction among young STEMI patients.

PMID- 26297337
TI  - Saccharicrinis marinus sp. nov., isolated from marine sediment.
AB  - A novel bacterial strain, designated Y11T, was isolated from marine sediment at
      Weihai in China. Comparative analysis of 16S rRNA gene sequences demonstrated
      that the novel isolate showed highest similarity to Saccharicrinis fermentans DSM
      9555T (94.0 %) and Saccharicrinis carchari SS12T (92.7 %). Strain Y11T was a Gram
      stain-negative, rod-shaped, non-endospore-forming, yellow-pigmented bacterium and
      was able to hydrolyse agar weakly. It was catalase-negative, oxidase-positive,
      facultatively anaerobic and motile by gliding. Optimal growth occurred at 28-30 
      degrees C, at pH 7.0-7.5 and in the presence of 2-3 % (w/v) NaCl. The DNA G+C
      content was 34.4 mol%. The strain contained MK-7 as the prevalent menaquinone.
      The major cellular fatty acids were iso-C15 : 0, anteiso-C15 : 0 and C15 :
      1omega6c. The predominant polar lipids were phosphatidylethanolamine and two
      unknown lipids. Data from the present polyphasic taxonomic study clearly place
      the strain as representing a novel species within the genus Saccharicrinis, for
      which the name Saccharicrinis marinus sp. nov. is proposed. The type strain is
      Y11T ( = CICC10837T = KCTC42400T). 

PMID- 26297339
TI  - Reply to Comment to: A systematic review of the surgical treatment of large
      incisional hernia. T. Georgiev-Hristov, A. Celdran. Hernia 2015; 19:89-101.

PMID- 26297338
TI  - IMonitor: A Robust Pipeline for TCR and BCR Repertoire Analysis.
AB  - The advance of next generation sequencing (NGS) techniques provides an
      unprecedented opportunity to probe the enormous diversity of the immune
      repertoire by deep sequencing T-cell receptors (TCRs) and B-cell receptors
      (BCRs). However, an efficient and accurate analytical tool is still on demand to
      process the huge amount of data. We have developed a high-resolution analytical
      pipeline, Immune Monitor ("IMonitor") to tackle this task. This method utilizes
      realignment to identify V(D)J genes and alleles after common local alignment. We
      compare IMonitor with other published tools by simulated and public rearranged
      sequences, and it demonstrates its superior performance in most aspects. Together
      with this, a methodology is developed to correct the PCR and sequencing errors
      and to minimize the PCR bias among various rearranged sequences with different V
      and J gene families. IMonitor provides general adaptation for sequences from all
      receptor chains of different species and outputs useful statistics and
      visualizations. In the final part of this article, we demonstrate its application
      on minimal residual disease detection in patients with B-cell acute lymphoblastic
      leukemia. In summary, this package would be of widespread usage for immune
      repertoire analysis. 

PMID- 26297340
TI  - On the Compressibility of Arterial Tissue.
AB  - Arterial tissue is commonly assumed to be incompressible. While this assumption
      is convenient for both experimentalists and theorists, the compressibility of
      arterial tissue has not been rigorously investigated. In the current study we
      present an experimental-computational methodology to determine the
      compressibility of aortic tissue and we demonstrate that specimens excised from
      an ovine descending aorta are significantly compressible. Specimens are stretched
      in the radial direction in order to fully characterise the mechanical behaviour
      of the tissue ground matrix. Additionally biaxial testing is performed to fully
      characterise the anisotropic contribution of reinforcing fibres. Due to the
      complexity of the experimental tests, which entail non-uniform finite deformation
      of a non-linear anisotropic material, it is necessary to implement an inverse
      finite element analysis scheme to characterise the mechanical behaviour of the
      arterial tissue. Results reveal that ovine aortic tissue is highly compressible;
      an effective Poisson's ratio of 0.44 is determined for the ground matrix
      component of the tissue. It is also demonstrated that correct characterisation of
      material compressibility has important implications for the calibration of
      anisotropic fibre properties using biaxial tests. Finally it is demonstrated that
      correct treatment of material compressibility has significant implications for
      the accurate prediction of the stress state in an artery under in vivo type
      loading. 

PMID- 26297341
TI  - Patient-Specific Biomechanical Modeling for Guidance During Minimally-Invasive
      Hepatic Surgery.
AB  - During the minimally-invasive liver surgery, only the partial surface view of the
      liver is usually provided to the surgeon via the laparoscopic camera. Therefore,
      it is necessary to estimate the actual position of the internal structures such
      as tumors and vessels from the pre-operative images. Nevertheless, such task can
      be highly challenging since during the intervention, the abdominal organs undergo
      important deformations due to the pneumoperitoneum, respiratory and cardiac
      motion and the interaction with the surgical tools. Therefore, a reliable
      automatic system for intra-operative guidance requires fast and reliable
      registration of the pre- and intra-operative data. In this paper we present a
      complete pipeline for the registration of pre-operative patient-specific image
      data to the sparse and incomplete intra-operative data. While the intra-operative
      data is represented by a point cloud extracted from the stereo-endoscopic images,
      the pre-operative data is used to reconstruct a biomechanical model which is
      necessary for accurate estimation of the position of the internal structures,
      considering the actual deformations. This model takes into account the patient
      specific liver anatomy composed of parenchyma, vascularization and capsule, and
      is enriched with anatomical boundary conditions transferred from an atlas. The
      registration process employs the iterative closest point technique together with
      a penalty-based method. We perform a quantitative assessment based on the
      evaluation of the target registration error on synthetic data as well as a
      qualitative assessment on real patient data. We demonstrate that the proposed
      registration method provides good results in terms of both accuracy and
      robustness w.r.t. the quality of the intra-operative data.

PMID- 26297342
TI  - High expression of DDR1 is associated with the poor prognosis in Chinese patients
      with pancreatic ductal adenocarcinoma.
AB  - BACKGROUND: Discoidin domain receptors 1 (DDR1), a subtype of DDRs, has been
      reported as a critical modulator of cellular morphogenesis, differentiation,
      migration and invasion. METHODS AND RESULTS: In this study, we investigated the
      expression of DDR1 and its clinical association in Chinese patients with
      pancreatic ductal adenocarcinoma (PDAC). Across a cohort of 30 patients, we
      examined DDR1 expression in paired PDAC and corresponding adjacent non-tumor
      tissues by real-time quantitative PCR (RT-qPCR), or western blotting. DDR1
      expression is significantly higher in PDAC, as compared to normal adjacent
      tissue, confirming results from the Oncomine databases. We validated DDR1
      expression by immunohistochemistry across a non-overlapping cohort of 205 PDAC
      specimens. Kaplan-Meier survival curves indicate that increased expression of
      DDR1 is associated with a poor prognosis in PDAC patients (P = 0.013).
      Multivariate Cox regression analysis identified DDR1 expression, age, N
      classification and liver metastasis as independent prognostic factors in PDAC.
      CONCLUSIONS: This study demonstrated that DDR1 can well serve as a novel
      prognostic biomarker in PDAC.

PMID- 26297343
TI  - Streptomyces mangrovi sp. nov., an actinomycete from mangrove soil.
AB  - A novel aerobic actinomycete, designated HA11110(T), was isolated from a mangrove
      soil sample collected in Haikou, China. It formed white aerial mycelium and pale
      yellow substrate mycelium on Gause's synthetic agar no. 1. Scanning electron
      microscopy revealed that cells of HA11110(T) produced straight to spiral spore
      chains with spiny spores. Chemotaxonomic tests showed that the cell wall
      contained LL-diaminopimelic acid and the major fatty acids were iso-C16 : 0,
      anteiso-C15 : 0 and iso-C14 : 0.16S rRNA gene sequence similarity showed that
      strain HA11110(T) belonged to the genus Streptomyces, most closely related to
      Streptomyces fenghuangensis GIMN4.003(T) (99.1%), Streptomyces nanhaiensis SCSIO
      01248(T) (98.8%) and Streptomyces radiopugnans R97(T) (98.8%). However, DNA-DNA
      hybridization studies of strain HA11110T with these three closest relatives
      showed relatedness values of 58.4, 49.7 and 47.2%, respectively. On the basis of
      phenotypic and genotypic data, strain HA11110(T) represents a novel species of
      the genus Streptomyces, for which the name Streptomyces mangrovi sp. nov. is
      proposed. The type strain is HA11110(T) ( = CGMCC 4.7117(T)= DSM 42113(T)).

PMID- 26297344
TI  - In vitro adaptation of SAV3 in cell culture correlates with reduced in vivo
      replication capacity and virulence to Atlantic salmon (Salmo salar L.) parr.
AB  - Salmonid alphavirus (SAV) is the causative agent of pancreas disease affecting
      Atlantic salmon and rainbow trout and causes a major burden to the aquaculture
      industry. This study describes a Norwegian subtype SAV3 virus isolate (SAV3-H10)
      subjected to serial passages in Chinook salmon embryo cells (CHSE-214) followed
      by Asian Grouper skin cells (AGK). Two passages from CHSE and one after transfer
      to AGK cells were chosen for further investigation, based on variation in degree
      and development of cytopathic effect (CPE). After plaque purification, several in
      vitro studies were performed. Cell viability after infection, viral replication
      and ability to cause morphological changes in CHSE and AGK cells was studied for
      the three isolates. The AGK-transferred isolate was identified with the strongest
      abilities to reduce cell viability, replicate more and cause more CPE in cell
      culture when compared with the early and late CHSE-grown isolates. Subsequently,
      the isolates were tested in an experimental fish challenge, showing higher viral
      load and higher pathological score for the least cell-cultured isolate. Full
      length sequencing of the viral genome of the three isolates revealed divergence
      in four amino acid positions and the AGK-grown isolate also had a 3 nt deletion
      in the 3'UTR. In conclusion, we show that cell culture of SAV3-H10 selects for
      strains inducing earlier CPE in vitro with increased viral replication. In vivo,
      the effect is reversed, with lower replication levels and lower pathology scores
      in target organs. This study outlines a path to identify potential virulence
      motifs of SAV3. 

PMID- 26297345
TI  - Michelangelo, the Last Judgment fresco, Saint Bartholomew and the Golden Ratio.
AB  - Art and anatomy were particularly closely intertwined during the Renaissance
      period and numerous painters and sculptors expressed themselves in both fields.
      Among them was Michelangelo Buonarroti (1475-1564), who is renowned for having
      produced some of the most famous of all works of art, the frescoes on the ceiling
      and on the wall behind the altar of the Sistine Chapel in Rome. Recently, a
      unique association was discovered between one of Michelangelo's most celebrated
      works (The Creation of Adam fresco) and the Divine Proportion/Golden Ratio (GR)
      (1.6). The GR can be found not only in natural phenomena but also in a variety of
      human-made objects and works of art. Here, using Image-Pro Plus 6.0 software, we
      present mathematical evidence that Michelangelo also used the GR when he painted
      Saint Bartholomew in the fresco of The Last Judgment, which is on the wall behind
      the altar. This discovery will add a new dimension to understanding the great
      works of Michelangelo Buonarroti.

PMID- 26297346
TI  - Anaerobium acetethylicum gen. nov., sp. nov., a strictly anaerobic, gluconate
      fermenting bacterium isolated from a methanogenic bioreactor.
AB  - A novel strictly anaerobic, mesophilic bacterium was enriched and isolated with
      gluconate as sole substrate from a methanogenic sludge collected from a biogas
      reactor. Cells of strain GluBS11T stained Gram-positive and were non-motile,
      straight rods, measuring 3.0-4.5 * 0.8-1.2 MUm. The temperature range for growth
      was 15-37  degrees C, with optimal growth at 30  degrees C, the pH range was 6.5
      8.5, with optimal growth at pH 7, and the generation time under optimal
      conditions was 60 min. API Rapid 32A reactions were positive for alpha
      galactosidase, alpha-glucosidase and beta-glucosidase and negative for catalase
      and oxidase. A broad variety of substrates was utilized, including gluconate,
      glucose, fructose, maltose, sucrose, lactose, galactose, melezitose, melibiose,
      mannitol, erythritol, glycerol and aesculin. Products of gluconate fermentation
      were ethanol, acetate, formate, H2 and CO2. Neither sulfate nor nitrate served as
      an electron acceptor. Predominant cellular fatty acids (>10 %) were C14 : 0, C16
      : 0, C16 : 1omega7c/iso-C15 : 0 2-OH and C18 : 1omega7c. The DNA G+C content of
      strain GluBS11T was 44.1 mol%. Phylogenetic analysis based on 16S rRNA gene
      sequence data revealed that strain GluBS11T is a member of subcluster XIVa within
      the order Clostridiales. The closest cultured relatives are Clostridium
      herbivorans (93.1 % similarity to the type strain), Clostridium populeti (93.3
      %), Eubacterium uniforme (92.4 %) and Clostridium polysaccharolyticum (91.5 %).
      Based on this 16S rRNA gene sequence divergence (>6.5 %) as well as on
      chemotaxonomic and phenotypic differences from these taxa, strain GluBS11T is
      considered to represent a novel genus and species, for which the name Anaerobium
      acetethylicum gen. nov., sp. nov. is proposed. The type strain of Anaerobium
      acetethylicum is GluBS11T ( = LMG 28619T = KCTC 15450T = DSM 29698T). 

PMID- 26297347
TI  - Using Videoconferencing Technology to Provide Breastfeeding Support to Low-Income
      Women: Connecting Hospital-Based Lactation Consultants with Clients Receiving
      Care at a Community Health Center.
AB  - The Tele-Lactation Pilot Project (TLPP), 1 of 13 community-based breastfeeding
      projects implemented in Indiana in 2013 using Centers for Disease Control and
      Prevention grant funds, explored the feasibility of using videoconferencing
      technology to provide breastfeeding education and support to low-income women by
      a centrally located International Board Certified Lactation Consultant (IBCLC).
      The IBCLC was housed at the Breastfeeding Center at the hospital where the women
      would deliver; the women receiving the education and support were located at an
      inner-city community health center (CHC) where they received their primary care.
      The videoconferencing sessions were juxtaposed with the women's regularly
      scheduled prenatal and postnatal visits at the CHC. After delivery, the lactation
      consultant visited the mother and infant in person at the hospital to offer
      additional support. Overall, 35 mothers were served by the TLPP during the 9
      month project period. A total of 134 visits (30-45 minutes each) were conducted
      (3.8 sessions per woman). At the conclusion of the project, interviews with key
      participants indicated that the tele-lactation videoconferencing sessions were
      easy to implement, allowed the IBCLC to reach a wider client base, and allowed
      the women to receive expert support that they might not have otherwise received.
      Comments indicated that, in addition to providing education and increasing the
      women's confidence, the tele-lactation sessions appeared to have decreased the
      mothers' anxiety about the birthing process and the hospital experience. The TLPP
      demonstrated that incorporating videoconferencing technology into routine care
      can help foster collaboration among health care providers and provide mothers
      with continuous, easily accessible breastfeeding education and support. 

PMID- 26297348
TI  - Role of thyrotropin-releasing hormone in prolactin-producing cell models.
AB  - Thyrotropin-releasing hormone (TRH) is a hypothalamic hypophysiotropic
      neuropeptide that was named for its ability to stimulate the release of thyroid
      stimulating hormone in mammals. It later became apparent that it exerts a number
      of species-dependent hypophysiotropic activities that regulate other pituitary
      hormones. TRH also regulates the synthesis and release of prolactin, although
      whether it is a physiological regulator of prolactin that remains unclear.
      Occupation of the Gq protein-coupled TRH receptor in the prolactin-producing
      lactotroph increases the turnover of inositol, which in turn activates the
      protein kinase C pathway and the release of Ca(2+) from storage sites. TRH
      induced signaling events also include the activation of extracellular signal
      regulated kinase (ERK) and induction of MAP kinase phosphatase, an inactivator of
      activated ERK. TRH stimulates prolactin synthesis through the activation of ERK,
      whereas prolactin release occurs via elevation of intracellular Ca(2+). We have
      been investigating the role of TRH in a pituitary prolactin-producing cell model.
      Rat pituitary somatolactotroph GH3 cells, which produce and release both
      prolactin and growth hormone (GH), are widely used as a model for the study of
      prolactin- and GH-secreting cells. In this review, we describe the general action
      of TRH as a hypophysiotropic factor in vertebrates and focus on the role of TRH
      in prolactin synthesis using GH3 cells. 

PMID- 26297349
TI  - The central anorexigenic mechanism of adrenocorticotropic hormone involves the
      caudal hypothalamus in chicks.
AB  - Adrenocorticotropic hormone (ACTH), consisting of 39 amino acids, is most well
      known for its involvement in an organism's response to stress. It also
      participates in satiety, as exogenous ACTH causes decreased food intake in rats.
      However, its anorexigenic mechanism is not well understood in any species and its
      effect on appetite is not reported in the avian class. Thus, the present study
      was designed to evaluate central ACTH's effect on food intake and to elucidate
      the mechanism mediating this response using broiler chicks. Chicks that received
      intracerebroventricular (ICV) injection of 1, 2, or 4 nmol of ACTH reduced food
      intake, under both ad libitum and 180 min fasted conditions. Water intake was
      also reduced in ACTH-injected chicks under both feeding conditions, but when
      measured without access to feed it was not affected. Blood glucose was not
      affected in either feeding condition. Following ACTH injection, c-Fos
      immunoreactivity was quantified in key appetite-associated hypothalamic nuclei
      including the ventromedial hypothalamus (VMH), dorsomedial hypothalamus, lateral
      hypothalamus (LH), arcuate nucleus (ARC) and the parvo- and magno-cellular
      portions of the paraventricular nucleus. ACTH-injected chicks had increased c-Fos
      immunoreactivity in the VMH, LH, and ARC. Hypothalamus was collected at 1h post
      injection, and real-time PCR performed to measure mRNA abundance of some appetite
      associated factors. Neuropeptide Y, pro-opiomelanocortin, glutamate decarboxylase
      1, melanocortin receptors 2-5, and urocortin 3 mRNA abundance was not affected by
      ACTH treatment. However, expression of corticotropin releasing factor (CRF),
      urotensin 2 (UT), agouti-related peptide (AgRP), and orexin (ORX), and
      melanocortin receptor 1 (MC1R) mRNA decreased in the hypothalamus of ACTH
      injected chicks. In conclusion, ICV ACTH causes decreased food intake in chicks,
      and is associated with VMH, LH, and ARC activation, and a decrease in
      hypothalamic mRNA abundance of CRF, UT, AgRP, ORX and MC1R.

PMID- 26297350
TI  - Acute, but not chronic, stress increased the plasma concentration and
      hypothalamic mRNA expression of NUCB2/nesfatin-1 in rats.
AB  - Nesfatin-1, a newly discovered satiety peptide, has recently been reported to be
      involved in the stress response. Stress-induced expression of nesfatin-1 has been
      reported and few studies focus on its expression in the hypothalamus, which is
      the center of the stress response. To test our hypothesis that peripheral and
      hypothalamic nesfatin-1 overexpression should play an important role in the
      stress response and the associated hyperactivity of hypothalamic-pituitary
      adrenal (HPA) axis, acute stress (AS) was induced using water avoidance stress
      (WAS), and chronic unpredictable mild stress (CUMS) was also induced using 3
      consecutive weeks of 7 different stressors. The behavior of CUMS rats was
      evaluated by an open field test (OFT), sucrose preference test (SPT), and forced
      swimming test (FST). The activity of the HPA axis was detected by measurement of
      the plasma corticosterone concentration and hypothalamic mRNA expression of
      corticotropin-releasing-hormone (CRH). The plasma concentration and hypothalamic
      mRNA expression of nesfatin-1 were measured with an enzyme-linked immunosorbent
      assay (ELISA) and real-time fluorescent quantitative PCR, respectively. The
      results showed that both AS and CUMS increased the plasma corticosterone
      concentration and hypothalamic CRH mRNA expression. Depression-like behavior was
      induced in CUMS rats, as indicated by a decreased movement distance, frequency of
      rearing and grooming in the OFT, and sucrose preference index and increased
      immobility in the FST. Moreover, the AS rats showed increased plasma
      concentration and hypothalamic mRNA expression of nesfatin-1, which were
      positively correlated with the plasma corticosterone concentration and
      hypothalamic CRH expression, respectively. These results indicated that acute
      stress, but not chronic stress, increased the plasma concentration and
      hypothalamic mRNA expression of NUCB2/nesfatin-1 in rats. 

PMID- 26297351
TI  - Atherosclerosis, neoatherosclerosis, and vascular disease.

PMID- 26297352
TI  - Proposals for data protection regulationen danger research in the European Union.

PMID- 26297353
TI  - Planococcus faecalis sp. nov., a carotenoid-producing species isolated from
      stools of Antarctic penguins.
AB  - Taxonomic studies were performed on a novel carotenoid-producing strain,
      designated AJ003T, isolated from faeces of Antarctic penguins. Cells of strain
      AJ003T were aerobic, Gram-stain-positive, cocci-shaped and orange. Strain AJ003T
      was capable of growing in a broad temperature range, including sub-zero growth
      (below - 20 to 30  degrees C). 16S rRNA gene sequence analysis revealed that
      strain AJ003T was closely related to Planococcus halocryophilus Or1T (97.4 %
      similarity), Planococcus antarcticus DSM 14505T (97.3 %), Planococcus kocurii
      NCIMB 629T (97.3 %), and Planococcus donghaensis JH1T (97.1 %). The predominant
      cellular fatty acids were anteiso-C15 : 0, and iso-C16 : 0.MK-7 and MK-8 were the
      quinones identified, and the major pigment was glycosyl-4,4'-diaponeurosporen-4'
      ol-4-oic acid. The major polar lipid was phosphatidylglycerol. DNA-DNA
      relatedness of strain AJ003T with respect to its closest phylogenetic neighbours
      was 38.2 +/- 0.5 % for Planococcus halocryophilus DSM 24743T, 32.2 +/- 0.2 % for
      Planococcus antarcticus DSM 14505T, 21.0 +/- 0.3 % for Planococcus kocurii DSM
      20747T and 18.6 +/- 1.4 % for Planococcus donghaensis KCTC 13050T. The DNA G+C
      content of strain AJ003T was 40.0 +/- 0.6 mol%. Based on the phenotypic,
      chemotaxonomic and phylogenetic data, strain AJ003T is concluded to represent a
      novel species of the genus Planococcus, for which the name Planococcus faecalis
      sp. nov. is proposed. The type strain is AJ003T ( = KCTC 33580T = CECT 8759T).

PMID- 26297354
TI  - Multiple roles of oxygen in the photoinactivation and dynamic repair of
      Photosystem II in spinach leaves.
AB  - Oxygen effects have long been ambiguous: exacerbating, being indifferent to, or
      ameliorating the net photoinactivation of Photosystem II (PS II). We scrutinized
      the time course of PS II photoinactivation (characterized by rate coefficient k
      i) in the absence of repair, or when recovery (characterized by k r) occurred
      simultaneously in CO2 +/- O2. Oxygen exacerbated photoinactivation per se, but
      alleviated it by mediating the utilization of electrons. With repair permitted,
      the gradual net loss of functional PS II during illumination of leaves was better
      described phenomenologically by introducing tau, the time for an initial k r to
      decrease by half. At 1500 MUmol photons m(-2) s(-1), oxygen decreased the initial
      k r but increased tau. Similarly, at even higher irradiance in air, there was a
      further decrease in the initial k r and increase in tau. These observations are
      consistent with an empirical model that (1) oxygen increased k i via oxidative
      stress but decreased it by mediating the utilization of electrons; and (2)
      reactive oxygen species stimulated the degradation of photodamaged D1 protein in
      PS II (characterized by k d), but inhibited the de novo synthesis of D1
      (characterized by k s), and that the balance between these effects determines the
      net effect of O2 on PS II functionality. 

PMID- 26297355
TI  - Expression of Raf kinase inhibitor protein is downregulated in response to
      Newcastle disease virus infection to promote viral replication.
AB  - Newcastle disease virus (NDV) causes a severe and economically significant
      disease affecting almost the entire poultry industry worldwide. However, factors
      that affect NDV replication in host cells are poorly understood. Raf kinase
      inhibitory protein (RKIP) is a physiological inhibitor of c-RAF kinase and NF
      kappaB signalling, known for their functions in the control of immune response as
      well as tumour invasion and metastasis. In the present study, we investigated the
      consequences of overexpression of host RKIP during viral infection. We
      demonstrate that NDV infection represses RKIP expression thereby promoting virus
      replication. Experimental upregulation of RKIP in turn acts as a potential
      antiviral defence mechanism in host cells that restricts NDV replication by
      repressing the activation of Raf/MEK/ERK and IkappaBalpha/NF-kappaB signalling
      pathways. Our results not only extend the concept of linking NDV-host
      interactions, but also reveal RKIP as a new class of protein-kinase-inhibitor
      protein that affects NDV replication with therapeutic potential. 

PMID- 26297356
TI  - Development and verification of the PAM50-based Prosigna breast cancer gene
      signature assay.
AB  - BACKGROUND: The four intrinsic subtypes of breast cancer, defined by differential
      expression of 50 genes (PAM50), have been shown to be predictive of risk of
      recurrence and benefit of hormonal therapy and chemotherapy. Here we describe the
      development of ProsignaTM, a PAM50-based subtype classifier and risk model on the
      NanoString nCounter Dx Analysis System intended for decentralized testing in
      clinical laboratories. METHODS: 514 formalin-fixed, paraffin-embedded (FFPE)
      breast cancer patient samples were used to train prototypical centroids for each
      of the intrinsic subtypes of breast cancer on the NanoString platform.
      Hierarchical cluster analysis of gene expression data was used to identify the
      prototypical centroids defined in previous PAM50 algorithm training exercises.
      304 FFPE patient samples from a well annotated clinical cohort in the absence of
      adjuvant systemic therapy were then used to train a subtype-based risk model
      (i.e. Prosigna ROR score). 232 samples from a tamoxifen-treated patient cohort
      were used to verify the prognostic accuracy of the algorithm prior to initiating
      clinical validation studies. RESULTS: The gene expression profiles of each of the
      four Prosigna subtype centroids were consistent with those previously published
      using the PCR-based PAM50 method. Similar to previously published classifiers,
      tumor samples classified as Luminal A by Prosigna had the best prognosis compared
      to samples classified as one of the three higher-risk tumor subtypes. The
      Prosigna Risk of Recurrence (ROR) score model was verified to be significantly
      associated with prognosis as a continuous variable and to add significant
      information over both commonly available IHC markers and Adjuvant! Online.
      CONCLUSIONS: The results from the training and verification data sets show that
      the FDA-cleared and CE marked Prosigna test provides an accurate estimate of the
      risk of distant recurrence in hormone receptor positive breast cancer and is also
      capable of identifying a tumor's intrinsic subtype that is consistent with the
      previously published PCR-based PAM50 assay. Subsequent analytical and clinical
      validation studies confirm the clinical accuracy and technical precision of the
      Prosigna PAM50 assay in a decentralized setting.

PMID- 26297357
TI  - Risk factors for under-5 mortality: evidence from Bangladesh Demographic and
      Health Survey, 2004-2011.
AB  - OBJECTIVE: The aim of this study was to identify factors associated with
      mortality in children under 5 years of age using a nationally representative
      sample of singleton births for the period of 2004-2011. DESIGN, SETTING AND
      PARTICIPANTS: Pooled 2004, 2007 and 2011 cross-sectional data sets of the
      Bangladesh Demographic and Health Surveys were analysed. The surveys used a
      stratified two-stage cluster sample of 16,722 singleton live-born infants of the
      most recent birth of a mother within a 3-year period. MAIN OUTCOME MEASURES:
      Outcome measures were neonatal mortality (0-30 days), postneonatal mortality (1
      11 months), infant mortality (0-11 months), child mortality (1-4 years) and under
      5 mortality (0-4 years). RESULTS: Survival information for 16,722 singleton live
      born infants and 522 deaths of children <5 years of age included: 310 neonatal
      deaths, 154 postneonatal deaths, 464 infant deaths, 58 child deaths and 522 under
      5 deaths. Multiple variable analysis showed that, over a 7-year period, mortality
      reduced significantly by 48% for postneonatal deaths, 33% for infant deaths and
      29% for under-5 deaths, but there was no significant reduction in neonatal deaths
      (adjusted OR (AOR) = 0.79, 95% CI 0.59 to 1.06) or child deaths (AOR = 1.00, 95%
      CI 0.51 to 1.94). The odds of neonatal, postneonatal, infant, child and under-5
      deaths decreased significantly among mothers who used contraceptive and mothers
      who had other children aged 3 years or older. The risk of neonatal, postneonatal,
      infant, child and under-5 deaths was significantly higher in mothers who reported
      a previous death of a sibling. CONCLUSIONS: Our study suggests that family
      planning is needed to further reduce the overall rate of under-5 deaths in
      Bangladesh. To reduce childhood mortality, public health interventions that focus
      on child spacing and contraceptive use by mothers may be most effective.

PMID- 26297358
TI  - The impact of distance and duration of travel on participation rates and
      participants' satisfaction: results from a pilot study at one study centre in
      Pretest 2 of the German National Cohort.
AB  - OBJECTIVES: In this pilot study within the Pretest 2 phase of the German National
      Cohort, we aimed to (1) test the hypothesis that distance and duration of travel
      to a study centre may affect participation rates and participants' satisfaction
      and (2) to obtain data that would help to select recruitment areas around the
      study centre Hannover with the greatest projected participation rate for the main
      study. SETTING: Mixed urban/suburban environment in Northern Germany with
      approximately 600,000 inhabitants. 4 recruitment areas with divergent estimated
      mean distances (range, 7-40 km) and duration of travel to the study centre
      Hannover were selected. PARTICIPANTS: 1050 men and women (ratio, 1:1), aged 20-69
      years, were randomly selected from the population registries of the 4 recruitment
      areas and invited by mail to participate in the Pretest 2 study programme at the
      study centre Hannover, covering a variety of questionnaire-based and physical
      assessments. 166 individuals participated (16%). INTERVENTIONS: All 166
      participants completed a travel questionnaire containing 5 items relating to
      travel duration and satisfaction, amounting to a participation rate of 100% in
      the questionnaire-based part of the study. RESULTS: Participation rates in the
      Pretest 2 programme at the study centre Hannover by area ranged from 11% (area
      farthest from the study centre, estimated median distance 38 km) to 18% (nearest
      area, 2 km). The odds of non-participation were highest in the area farthest from
      the study centre (adjusted OR 2.06; p=0.01; CI 1.28 to 3.32). Nonetheless, 97% of
      participants were satisfied with travel duration. CONCLUSIONS: Increasing
      distance was associated with a lower participation rate. However, acceptance of
      duration of travel was high, irrespective of distance or duration. Thus,
      recruiting in farther away locations may select individuals with a greater
      frustration tolerance for travel to the study centre, perhaps due to a greater
      interest in participating in health-oriented studies and thus different health
      related behaviour.

PMID- 26297359
TI  - Role of overweight and obesity in low back disorders among men: a longitudinal
      study with a life course approach.
AB  - OBJECTIVES: To assess the association between being overweight or obese with low
      back pain (LBP) and clinically defined low back disorders across the life course.
      DESIGN: A longitudinal and cross-sectional study. SETTING: A nationwide health
      survey supplemented with data from records of prior compulsory military service.
      PARTICIPANTS: Premilitary health records (baseline) were searched for men aged 30
      50 years (n=1385) who participated in a national health examination survey
      (follow-up). METHODS AND OUTCOME MEASURES: Height and weight were measured at
      baseline and follow-up, and waist circumference at follow-up. Weight at the ages
      of 20, 30, 40 and 50 years were ascertained, when applicable. Repeated measures
      of weight were used to calculate age-standardised mean body mass index (BMI)
      across the life course. The symptom-based outcome measures at follow-up included
      prevalence of non-specific and radiating LBP during the previous 30 days. The
      clinically defined outcome measures included chronic low back syndrome and
      sciatica. RESULTS: Baseline BMI (20 years) predicted radiating LBP in adulthood,
      with the prevalence ratio (PR) being 1.26 (95% CI 1.08 to 1.46) for one SD (3.0
      kg/m(2)) increase in BMI. Life course BMI was associated with radiating LBP
      (PR=1.23; 95% CI 1.03 to 1.48 per 1 unit increment in Z score, corresponding to
      2.9 kg/m(2)). The development of obesity during follow-up increased the risk of
      radiating LBP (PR=1.91, 95% CI 1.03 to 3.53). Both general and abdominal obesity
      (defined as waist-to-height ratio) were associated with radiating LBP (OR=1.64,
      95% CI 1.02 to 2.65 and 1.44, 95% CI 1.02 to 2.04). No associations were seen for
      non-specific LBP. CONCLUSIONS: Our findings imply that being overweight or obese
      in early adulthood as well as during the life course increases the risk of
      radiating but not non-specific LBP among men. Taking into account the current
      global obesity epidemic, emphasis should be placed on preventive measures
      starting at youth and, also, measures for preventing further weight gain during
      the life course should be implemented.

PMID- 26297360
TI  - Remote ischaemic conditioning on recipients of deceased renal transplants, effect
      on immediate and extended kidney graft function: a multicentre, randomised
      controlled trial protocol (CONTEXT).
AB  - INTRODUCTION: Delayed graft function due to ischaemia-reperfusion injury is a
      frequent complication in deceased donor renal transplantation. Experimental
      evidence indicates that remote ischaemic conditioning (RIC) provides systemic
      protection against ischaemia-reperfusion injury in various tissues. METHODS AND
      ANALYSIS: 'Remote ischaemic conditioning in renal transplantation--effect on
      immediate and extended kidney graft function' (the CONTEXT study) is an
      investigator initiated, multicentre, randomised controlled trial investigating
      whether RIC of the leg of the recipient improves short and long-term graft
      function following deceased donor kidney transplantation. The study will include
      200 kidney transplant recipients of organ donation after brain death and 20
      kidney transplant recipients of organ donation after circulatory death.
      Participants are randomised in a 1:1 design to RIC or sham-RIC (control). RIC
      consists of four cycles of 5 min occlusion of the thigh by a tourniquet inflated
      to 250 mm Hg, separated by 5 min of deflation. Primary end point is the time to a
      50% reduction from the baseline plasma creatinine, estimated from the changes of
      plasma creatinine values 30 days post-transplant or 30 days after the last
      performed dialysis post-transplant. Secondary end points are: need of dialysis
      post-transplant, measured and estimated-glomerular filtration rate (GFR) at 3 and
      12 months after transplantation, patient and renal graft survival, number of
      rejection episodes in the first year, and changes in biomarkers of acute kidney
      injury and inflammation in plasma, urine and graft tissue. ETHICS AND
      DISSEMINATION: The study is approved by the local ethical committees and national
      data security agencies. Results are expected to be published in 2016. TRIAL
      REGISTRATION NUMBER: NCT01395719.

PMID- 26297361
TI  - RITPBC: B-cell depleting therapy (rituximab) as a treatment for fatigue in
      primary biliary cirrhosis: study protocol for a randomised controlled trial.
AB  - INTRODUCTION: Primary biliary cirrhosis (PBC) is an autoimmune liver disease with
      approximately 50% of patients experiencing fatigue. This can be a particularly
      debilitating symptom, affecting quality of life and resulting in social
      isolation. Fatigue is highlighted by patients as a priority for research and
      patient support groups were involved in designing this trial. This is the first
      randomised controlled trial to investigate a treatment for fatigue in PBC. The
      trial protocol is innovative as it utilises novel magnetic resonance spectroscopy
      (MRS) techniques as an outcome measure. The protocol will be valuable to research
      groups planning clinical trials targeting fatigue in PBC and also transferrable
      to other conditions associated with fatigue. METHODS AND ANALYSIS: RITPBC is a
      Medical Research Council (MRC) and National Institute for Health Research (NIHR)
      Efficacy and Mechanism Evaluation Programme (EME)-funded project. It is a phase
      II, single-centre, randomised controlled, double-blinded trial comparing
      rituximab with placebo in fatigued PBC patients. 78 patients with PBC and
      moderate to severe fatigue will be randomised to receive two infusions of
      rituximab or placebo. The study aims to assess whether rituximab improves fatigue
      in patients with PBC, the safety, and tolerability of rituximab in PBC and the
      sustainability of any beneficial actions. The primary outcome will be an
      improvement in fatigue domain score of the PBC-40, a disease-specific quality of
      life measure, evaluated at 12-week assessment. Secondary outcome measures include
      novel MRS techniques assessing muscle bioenergetic function, physical activity,
      anaerobic threshold and symptom, and quality of life measures. The trial started
      recruiting in October 2012 and recruitment is ongoing. ETHICS AND DISSEMINATION:
      The trial has ethical approval from the NRES Committee North East, has Clinical
      Trial Authorisation from MHRA and local R&D approval. Trial results will be
      communicated to participants, presented at national and international meetings
      and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER:
      ISRCTN03978701.

PMID- 26297362
TI  - Association between lymphocyte-to-monocyte ratio (LMR) and the mortality of HBV
      related liver cirrhosis: a retrospective cohort study.
AB  - OBJECTIVE: Infection with hepatitis B virus (HBV) remains a major cause of liver
      cirrhosis (LC) in China. Recent reports suggest that the lymphocyte-to-monocyte
      ratio (LMR) is a potential biomarker for predicting clinical outcomes. In our
      study, we investigated if LMR can be used as a prognostic marker of mortality in
      patients with HBV-related LC. DESIGN: A retrospective cohort study. SETTING: HBV
      infected patients with LC and patients with chronic hepatitis B infection (CHB)
      from the Department of Infectious Disease were enrolled and 240 healthy
      individuals were recruited from the healthcare centre at the First Affiliated
      Hospital of Zhejiang University. PARTICIPANTS: 479 HBV-infected patients with LC,
      134 patients with CHB and 240 healthy individuals were enrolled. PRIMARY AND
      SECONDARY OUTCOME MEASURES: The receiver operating characteristic (ROC) curve and
      multivariable logistic regression analysis after adjusting for total protein,
      albumin, total bilirubin and the model for end-stage liver disease (MELD) score
      were used to evaluate the power of LMR for predicting 1 year mortality in
      patients with LC. RESULTS: The LMR was statistically lower in patients with LC.
      The MELD score and mortality were statistically higher in patients with LC
      compared with the CHB and control groups. The area under the ROC curve, cut-off
      values, sensitivity and specificity of LMR for predicting mortality LC in the
      training cohort were 0.817 (95% CI 0.746 to 0.888; p<0.001), 2.10, 82.6 and
      78.8%, and these data were confirmed in the validation cohort. The multivariate
      logistic regression analysis showed that LMR was an independent predictive factor
      of mortality in LC (OR 2.370, 95% CI (1.070 to 5.249); p=0.033). CONCLUSIONS: Our
      results strongly suggest that low LMR can be considered as an independent
      biomarker for predicting mortality in patients with LC.

PMID- 26297363
TI  - Data linkage errors in hospital administrative data when applying a
      pseudonymisation algorithm to paediatric intensive care records.
AB  - OBJECTIVES: Our aim was to estimate the rate of data linkage error in Hospital
      Episode Statistics (HES) by testing the HESID pseudoanonymisation algorithm
      against a reference standard, in a national registry of paediatric intensive care
      records. SETTING: The Paediatric Intensive Care Audit Network (PICANet) database,
      covering 33 paediatric intensive care units in England, Scotland and Wales.
      PARTICIPANTS: Data from infants and young people aged 0-19 years admitted between
      1 January 2004 and 21 February 2014. PRIMARY AND SECONDARY OUTCOME MEASURES:
      PICANet admission records were classified as matches (records belonging to the
      same patient who had been readmitted) or non-matches (records belonging to
      different patients) after applying the HESID algorithm to PICANet records. False
      match and missed-match rates were calculated by comparing results of the HESID
      algorithm with the reference standard PICANet ID. The effect of linkage errors on
      readmission rate was evaluated. RESULTS: Of 166,406 admissions, 88,596 were true
      matches (where the same patient had been readmitted). The HESID pseudonymisation
      algorithm produced few false matches (n=176/77,810; 0.2%) but a larger proportion
      of missed matches (n=3609/88,596; 4.1%). The true readmission rate was
      underestimated by 3.8% due to linkage errors. Patients who were younger, male,
      from Asian/Black/Other ethnic groups (vs White) were more likely to experience a
      false match. Missed matches were more common for younger patients, for
      Asian/Black/Other ethnic groups (vs White) and for patients whose records had
      missing data. CONCLUSIONS: The deterministic algorithm used to link all episodes
      of hospital care for the same patient in England has a high missed match rate
      which underestimates the true readmission rate and will produce biased analyses.
      To reduce linkage error, pseudoanonymisation algorithms need to be validated
      against good quality reference standards. Pseudonymisation of data 'at source'
      does not itself address errors in patient identifiers and the impact these errors
      have on data linkage.

PMID- 26297364
TI  - Accessing primary care Big Data: the development of a software algorithm to
      explore the rich content of consultation records.
AB  - OBJECTIVE: To develop a natural language processing software inference algorithm
      to classify the content of primary care consultations using electronic health
      record Big Data and subsequently test the algorithm's ability to estimate the
      prevalence and burden of childhood respiratory illness in primary care. DESIGN:
      Algorithm development and validation study. To classify consultations, the
      algorithm is designed to interrogate clinical narrative entered as free text,
      diagnostic (Read) codes created and medications prescribed on the day of the
      consultation. SETTING: Thirty-six consenting primary care practices from a mixed
      urban and semirural region of New Zealand. Three independent sets of 1200 child
      consultation records were randomly extracted from a data set of all general
      practitioner consultations in participating practices between 1 January 2008-31
      December 2013 for children under 18 years of age (n=754,242). Each consultation
      record within these sets was independently classified by two expert clinicians as
      respiratory or non-respiratory, and subclassified according to respiratory
      diagnostic categories to create three 'gold standard' sets of classified records.
      These three gold standard record sets were used to train, test and validate the
      algorithm. OUTCOME MEASURES: Sensitivity, specificity, positive predictive value
      and F-measure were calculated to illustrate the algorithm's ability to replicate
      judgements of expert clinicians within the 1200 record gold standard validation
      set. RESULTS: The algorithm was able to identify respiratory consultations in the
      1200 record validation set with a sensitivity of 0.72 (95% CI 0.67 to 0.78) and a
      specificity of 0.95 (95% CI 0.93 to 0.98). The positive predictive value of
      algorithm respiratory classification was 0.93 (95% CI 0.89 to 0.97). The positive
      predictive value of the algorithm classifying consultations as being related to
      specific respiratory diagnostic categories ranged from 0.68 (95% CI 0.40 to 1.00;
      other respiratory conditions) to 0.91 (95% CI 0.79 to 1.00; throat infections).
      CONCLUSIONS: A software inference algorithm that uses primary care Big Data can
      accurately classify the content of clinical consultations. This algorithm will
      enable accurate estimation of the prevalence of childhood respiratory illness in
      primary care and resultant service utilisation. The methodology can also be
      applied to other areas of clinical care.

PMID- 26297365
TI  - Trends and risk factors for HIV, HCV and syphilis seroconversion among drug users
      in a methadone maintenance treatment programme in China: a 7-year retrospective
      cohort study.
AB  - OBJECTIVE: This study explores the trends and associated factors of HIV,
      hepatitis C virus (HCV) and syphilis seroconversion among Chinese methadone
      maintenance treatment (MMT) clients over a follow-up period of up to 7 years.
      DESIGN: Drug users from 14 MMT clinics in Guangdong Province were recruited
      during 2006-2014. Participants were seronegative with at least one HIV, HCV or
      syphilis infection at baseline and had completed at least one follow-up test
      during the study period. We estimated HIV, HCV and syphilis seroconversion rates
      in follow-up years and identified the underlying predictors using a multivariate
      Cox regression model. RESULTS: Among 9240 participants, the overall HIV
      seroconversion rate was 0.20 (0.13 to 0.28)/100 person-years (pys), 20.54 (18.62
      to 22.46)/100 pys for HCV and 0.77 (0.62 to 0.93)/100 pys for syphilis, over the
      study period. HIV seroconversion rate showed a moderate but non-significant
      annual decline of 13.34% (-42.48% to 30.56%) (chi(2) trend test; p=0.369),
      whereas the decline of HCV seroconversion was 16.12% (5.53% to 25.52%) per annum
      (p<0.001). Syphilis seroconversion rate remained stable (p=0.540). Urine results
      positive for opioid predicted HIV seroconversion (>= 60% vs <60%; HR=3.40, 1.07
      to 10.85), being unmarried (HR=1.59, 1.15 to 2.20), injection drug use in the
      past 30 days (HR=2.17, 1.42 to 3.32), having sexual intercourse in the past 3
      months (HR=1.74, 1.22 to 2.47) and higher daily dosage of methadone (>= 60 mL vs
      <60 mL; HR=1.40, 1.01 to 1.94) predicted HCV seroconversion. Being female
      (HR=3.56, 2.25 to 5.64) and infected with HCV at baseline (HR=2.40, 1.38 to 8.36)
      were associated with subsequent syphilis seroconversion. CONCLUSIONS: MMT in
      China has demonstrated moderate-to-good effectiveness in reducing HIV and HCV
      incidence but not syphilis infection among participating drug users.

PMID- 26297366
TI  - Protocol for an overview of systematic reviews of interventions to reduce
      unscheduled hospital admissions among adults.
AB  - INTRODUCTION: Unscheduled hospital admissions are an increasing burden on health
      systems worldwide. To date, initiatives to reduce admissions have had limited
      success as it is unclear which strategies effectively reduce admissions and are
      supported by a strong evidence-base. Therefore, we will conduct an overview to
      find, assess and summarise all published peer-reviewed systematic reviews of
      randomised controlled trials that examine the effect of an intervention on
      unplanned admissions among adults. METHODS AND ANALYSIS: This is a protocol for a
      systematic overview of reviews. We will search four databases: Ovid MEDLINE,
      PubMed, Cochrane Database of Systematic Reviews and the Cochrane Database of
      Abstracts of Reviews of Effects. We will consider systematic reviews and meta
      analyses of randomised controlled trials in adults (>= 16 years old) evaluating
      the effect of any intervention on unscheduled hospital admissions including those
      to treat, monitor, diagnose or prevent a health problem. We will only include
      reviews that identified unscheduled hospitalisations as a prespecified outcome.
      Two authors will independently screen articles for inclusion using a priori
      criteria. We will assess the quality of included reviews and extract ratings of
      the quality of evidence from within each review. We will create a hierarchical
      list of interventions based on estimates of absolute admission reductions and the
      quality of the evidence. Presentation of results will align with guidelines in
      the Cochrane Handbook of Systematic Reviews of Interventions and the Preferred
      Reporting Items for Systematic Reviews and Meta-Analysis statement. ETHICS AND
      DISSEMINATION: Ethics approval is not required. We will submit the results of
      this study for peer-review publication. The results will inform future research
      and could be used by healthcare managers, administrators and policymakers to
      guide resource allocation decisions and inform local implementation and
      optimisation of interventions to reduce unscheduled hospital admissions.

PMID- 26297367
TI  - Perceptions of healthcare professionals and managers regarding the effectiveness
      of GP-led walk-in centres in the UK.
AB  - OBJECTIVES: This study aimed to identify the perceptions of healthcare
      professionals regarding the effectiveness and the impact of a new general
      practitioner-led (GP-led) walk-in centre in the UK. SETTING: This qualitative
      study was conducted in a large city in the North of England. In the past few
      years, there has been particular concern about an increase in the use of
      emergency department (ED) services provided by the National Health Service and
      part of the rationale for introducing the new GP-led walk-in centres has been to
      stem this increase. The five institutes included in the study were EDs, a minor
      injuries unit, a primary care trust, a GP-led walk-in centre and GP surgeries.
      PARTICIPANTS: Semistructured interviews were conducted with healthcare providers
      at an adult ED, an ED at a children's hospital, a minor injuries unit, a GP-led
      walk-in centre, GPs from surrounding surgeries and GPs. RESULTS: 11 healthcare
      professionals and managers were interviewed. Seven key themes were identified
      within the data: the clinical model of the GP-led walk-in centre; public
      awareness of the services; appropriate use of the centre; the impact of the
      centre on other services; demand for healthcare services; choice and confusion
      and mixed views (positive and negative) of the walk-in services. There were
      discrepancies between the managers and healthcare professionals regarding the
      usefulness of the GP-led walk-in centre in the current urgent care system.
      CONCLUSIONS: Participants did not notice declines in the demand for EDs after the
      GP-led walk-in centre. Most of the healthcare professionals believed that the GP
      led walk-in centre duplicated existing healthcare services. There is a need to
      have a better communication system between the GP-led walk-in centres and other
      healthcare providers to have an integrated system of urgent care delivery.

PMID- 26297368
TI  - The long-term effect of minimalist shoes on running performance and injury:
      design of a randomised controlled trial.
AB  - INTRODUCTION: The outcome of the effects of transitioning to minimalist running
      shoes is a topic of interest for runners and scientists. However, few studies
      have investigated the longer term effects of running in minimalist shoes. The
      purpose of this randomised controlled trial (RCT) is to investigate the effects
      of a 26 week transition to minimalist shoes on running performance and injury
      risk in trained runners unaccustomed to minimalist footwear. METHODS AND
      ANALYSIS: A randomised parallel intervention design will be used. Seventy-six
      trained male runners will be recruited. To be eligible, runners must be aged 18
      40 years, run with a habitual rearfoot footfall pattern, train with conventional
      shoes and have no prior experience with minimalist shoes. Runners will complete a
      standardised transition to either minimalist or control shoes and undergo
      assessments at baseline, 6 and 26 weeks. 5 km time-trial performance (5TT),
      running economy, running biomechanics, triceps surae muscle strength and lower
      limb bone mineral density will be assessed at each time point. Pain and injury
      will be recorded weekly. Training will be standardised during the first 6 weeks.
      Primary statistical analysis will compare 5TT between shoe groups at the 6-week
      time point and injury incidence across the entire 26-week study period. ETHICS
      AND DISSEMINATION: This RCT has been approved by the Human Research Ethics
      Committee of the University of South Australia. Participants will be required to
      provide their written informed consent prior to participation in the study. Study
      findings will be disseminated in the form of journal publications and conference
      presentations after completion of planned data analysis. TRIAL REGISTRATION
      NUMBER: This RCT has been registered with the Australian New Zealand Clinical
      Trials Registry (ACTRN12613000642785).

PMID- 26297369
TI  - Protocol for updating a systematic review of randomised controlled trials on the
      prophylactic use of intravenous immunoglobulin for patients undergoing
      haematopoietic stem cell transplantation.
AB  - INTRODUCTION: Haematopoietic stem cell transplantation (HSCT) is commonly
      employed in the management of haematological malignancies. This intervention
      results in an increased risk of infectious and immune-related complications.
      Prophylactic immunoglobulin therapy has been used to prevent post-HSCT
      complications, including infections, with varying efficacy. We sought to update
      the current evidence supporting the use of immunoglobulins in the modern HSCT
      era. METHODS/ANALYSIS: Using a structured search strategy, we will perform a
      systematic review of the literature from MEDLINE, EMBASE and all EBM Reviews
      databases. We will include randomised clinical trials investigating clinical
      outcomes of prophylactic polyvalent immunoglobulin or cytomegalovirus (CMV)
      specific immunoglobulin or plasma in patients undergoing HSCT. Clinical outcomes
      will include overall survival, transplant-related mortality, CMV infection, CMV
      disease, graft-versus-host disease, interstitial pneumonitis/fibrosis and hepatic
      veno-occlusive disease. Studies that only reported the results of biochemical
      tests will be excluded. Data will be extracted by two investigators
      independently. Study quality assessment will be evaluated using a validated five
      point system as proposed by Jadad. Trial quality will be further assessed by
      identifying whether there was adequate allocation concealment. Where appropriate,
      a meta-analysis will be performed where relative risk will be used as the primary
      summary measure with 95% CIs. Pooled measures will be calculated for randomised
      clinical trials using a random-effects model. The Cochrane Q/chi(2) test and I(2)
      statistic will also be calculated to evaluate heterogeneity. We will also use a
      visual inspection of a funnel plot to assess potential publication bias.
      DISCUSSION: This systematic review aims to provide current evidence to justify
      the use of immunoglobulin prophylaxis in HSCT recipients. We will discuss whether
      current HSCT guidelines are supported by the current evidence, and whether
      further trials are needed, given the changing landscape of patients undergoing
      HSCT and the immunoglobulin manufacturing process. SYSTEMATIC REVIEW
      REGISTRATION: PROSPERO CRD42015016684.

PMID- 26297370
TI  - Aortic dissection in pregnancy in England: an incidence study using linked
      national databases.
AB  - OBJECTIVES: To conduct the first population-level incidence study of aortic
      dissection in pregnancy using linked hospital-based data in England. SETTING:
      Hospital-based data (Hospital Episode Statistics (HES) linked with mortality data
      from the Office of National Statistics), national enquiries (Confidential
      Enquiries into Maternal Mortality) and surveys (UK Obstetric Surveillance System;
      UKOSS) of aortic dissection in pregnancy from 2003 to 2011 in England.
      PARTICIPANTS: Between 2003 and 2011, all female patients admitted with diagnoses
      of aortic dissection (not necessarily as the primary cause of admission) and of
      pregnancy, childbirth and puerperium, were included. OUTCOME MEASURES: Diagnosis
      of aortic dissection during pregnancy, operated or not operated, with outcome of
      death or live patient from 2003 to 2011 in England. RESULTS: There were
      significant differences in characteristics of databases with respect to study
      population, time of study, recorded event and follow-up of outcomes. On the basis
      of HES, annual incidence of aortic dissection was 1.23 (95% CI 1.22 to 1.24) per
      100 000 maternities. Incidence of aortic dissection with death within 1 year was
      0.30 (0.29 to 0.31) per 100 000 maternities. Incidence of aortic dissection
      increased from 0.74 (0.73 to 0.75) per 100 000 maternities in 2003-2005 to 1.52
      (1.51 to 1.53) per 100 000 maternities in 2009-2011. In the Confidential
      Enquiries into Maternal Deaths, incidence of deaths was highest for 2003-2005
      (0.43/100 000 maternities) and lowest for 1997-1999 (0.21/100 000 maternities).
      In the UK Obstetric Surveillance System, national incidence of aortic dissection
      was 0.80 (0.50 to 1.50) per 100 000 maternities between 2009 and 2011.
      CONCLUSIONS: The case of aortic dissection in pregnancy illustrates data
      limitations regarding complications in pregnancy from different sources in the
      UK, even for a diagnosis with seemingly few alternative coding and diagnostic
      possibilities. These limitations should be acknowledged when estimating incidence
      and outcome.

PMID- 26297371
TI  - Combined exercise and transcranial direct current stimulation intervention for
      knee osteoarthritis: protocol for a pilot randomised controlled trial.
AB  - INTRODUCTION: Osteoarthritis (OA) is a major health problem and a leading cause
      of disability. The knee joint is commonly affected, resulting in pain and
      physical dysfunction. Exercise is considered the cornerstone of conservative
      management, yet meta-analyses indicate, at best, moderate effect sizes.
      Treatments that bolster the effects of exercise, such as transcranial direct
      current stimulation (tDCS), may improve outcomes in knee OA. The aims of this
      pilot study are to (1) determine the feasibility, safety and perceived patient
      response to a combined tDCS and exercise intervention in knee OA, and (2) provide
      data to support a sample size calculation for a fully-powered trial should trends
      of effectiveness be present. METHODS AND ANALYSIS: A pilot randomised, assessor
      blind and participant-blind, sham-controlled trial. 20 individuals with knee OA
      who report a pain score of 40 or more on a 100 mm visual analogue scale on
      walking, and meet a priori selection criteria will be randomly allocated to
      receive either: (1) active tDCS plus exercise, or (2) sham tDCS plus exercise.
      All participants will receive 20 min of either active or sham tDCS immediately
      prior to 30 min of supervised muscle strengthening exercise twice a week for 8
      weeks. Participants in both groups will also complete unsupervised home exercises
      twice per week. Outcome measures of feasibility, safety, pain, disability and
      pain system function will be assessed immediately before and after the 8-week
      intervention. Analyses of feasibility and safety will be performed using
      descriptive statistics. Statistical analyses will be used to determine trends of
      effectiveness and will be based on intention-to-treat as well as per protocol.
      ETHICS AND DISSEMINATION: This study was approved by the institutional ethics
      committee (H10184). Written informed consent will be obtained from all
      participants. The results of this study will be submitted for peer-reviewed
      publication. TRIAL REGISTRATION NUMBER: ANZCTR365331.

PMID- 26297372
TI  - Characteristics of women who practice yoga in different locations during
      pregnancy.
AB  - OBJECTIVES: Yoga practice during pregnancy is gaining increasing popularity. This
      study examined the characteristics of pregnant women who practiced yoga in regard
      to the different locations (at home, in yoga classes, or both). DESIGN: The study
      sample was drawn from the Australian Longitudinal Study on Women's Health
      (ALSWH), a national longitudinal study of women to investigate multiple factors
      affecting health and well-being of women over a 20-year period. SETTING: Postal
      survey. PARTICIPANTS: Women born between 1973 and 1978, who were randomly
      selected from the national Medicare database and identified as being pregnant or
      having recently given birth (n=2316). OUTCOME MEASURES: Relationships between
      yoga use (attending yoga classes and/or practising yoga at home) and women's
      characteristics (demographic measures, pregnancy-related health concerns, health
      service utilisation, attitudes to complementary and alternative medicine).
      RESULTS: Practising yoga both at home and in classes was associated with
      perceiving complementary and alternative medicine (CAM) as preventative (odds
      ratio (OR)=1.62); perceiving CAM as affording health control (OR=1.50);
      experiencing sadness (OR=1.72); preparing for labour (OR=2.31); birthing in a
      birth centre (OR=7.97); and experiencing less vomiting (OR=0.38). Practising at
      home only was associated with perceiving CAM as affording health control
      (OR=1.76); perceiving CAM as promoting a holistic health approach (OR=1.65); and
      birthing in a birth centre (OR=3.54). Practising in classes only was associated
      with experiencing stress (OR=1.97); and birthing in a birth centre (OR=4.85) (all
      p<0.05). CONCLUSIONS: The findings suggest that the location in which a woman
      practices yoga is associated with attitudinal, health-related and birth
      environmental factors.

PMID- 26297373
TI  - Mortality from treatable illnesses in marginally housed adults: a prospective
      cohort study.
AB  - OBJECTIVES: Socially disadvantaged people experience greater risk for illnesses
      that may contribute to premature death. This study aimed to evaluate the impact
      of treatable illnesses on mortality among adults living in precarious housing.
      DESIGN: A prospective cohort based in a community sample. SETTING: A socially
      disadvantaged neighbourhood in Vancouver, Canada. PARTICIPANTS: Adults (N=371)
      living in single room occupancy hotels or recruited from the Downtown Community
      Court and followed for median 3.8 years. MAIN OUTCOME MEASURES: Participants were
      assessed for physical and mental illnesses for which treatment is currently
      available. We compared cohort mortality rates with 2009 Canadian rates. Left
      truncated Cox proportional hazards modelling with age as the time scale was used
      to assess risk factors for earlier mortality. RESULTS: During 1269 person-years
      of observation, 31/371 (8%) of participants died. Compared with age-matched and
      sex-matched Canadians, the standardised mortality ratio was 8.29 (95% CI 5.83 to
      11.79). Compared with those that had cleared the virus, active hepatitis C
      infection was a significant predictor for hepatic fibrosis adjusting for alcohol
      dependence and age (OR=2.96, CI 1.37 to 7.08). Among participants <55 years of
      age, psychosis (HR=8.12, CI 1.55 to 42.47) and hepatic fibrosis (HR=13.01, CI
      3.56 to 47.57) were associated with earlier mortality. Treatment rates for these
      illnesses were low (psychosis: 32%, hepatitis C virus: 0%) compared with other
      common disorders (HIV: 57%, opioid dependence: 61%) in this population.
      CONCLUSIONS: Hepatic fibrosis and psychosis are associated with increased
      mortality in people living in marginal conditions. Timely diagnosis and
      intervention could reduce the high mortality in marginalised inner city
      populations.

PMID- 26297374
TI  - Community IntraVenous Antibiotic Study (CIVAS): protocol for an evaluation of
      patient preferences for and cost-effectiveness of community intravenous
      antibiotic services.
AB  - INTRODUCTION: Outpatient parenteral antimicrobial therapy (OPAT) is used to treat
      a wide range of infections, and is common practice in countries such as the USA
      and Australia. In the UK, national guidelines (standards of care) for OPAT
      services have been developed to act as a benchmark for clinical monitoring and
      quality. However, the availability of OPAT services in the UK is still patchy and
      until quite recently was available only in specialist centres. Over time,
      National Health Service (NHS) Trusts have developed OPAT services in response to
      local needs, which has resulted in different service configurations and models of
      care. However, there has been no robust examination comparing the cost
      effectiveness of each service type, or any systematic examination of patient
      preferences for services on which to base any business case decision. METHODS AND
      ANALYSIS: The study will use a mixed methods approach, to evaluate patient
      preferences for and the cost-effectiveness of OPAT service models. The study
      includes seven NHS Trusts located in four counties. There are five inter-related
      work packages: a systematic review of the published research on the safety,
      efficacy and cost-effectiveness of intravenous antibiotic delivery services; a
      qualitative study to explore existing OPAT services and perceived barriers to
      future development; an economic model to estimate the comparative value of four
      different community intravenous antibiotic services; a discrete choice experiment
      to assess patient preferences for services, and an expert panel to agree which
      service models may constitute the optimal service model(s) of community
      intravenous antibiotics delivery. ETHICS AND DISSEMINATION: The study has been
      approved by the NRES Committee, South West-Frenchay using the Proportionate
      Review Service (ref 13/SW/0060). The results of the study will be disseminated at
      national and international conferences, and in international journals.

PMID- 26297376
TI  - The impact of PCR on Clostridium difficile detection and clinical outcomes.
AB  - PCR has increasingly replaced toxin A and B enzyme immunoassay (EIA) for the
      testing of Clostridium difficile infection (CDI). This study evaluated the
      clinical outcomes of CDI and disease epidemiology since the introduction of PCR.
      Clinical data and outcomes for patients admitted to a tertiary care centre during
      2003 to 2012 were extracted using electronic medical records. Outcomes and
      incidence of disease were compared between types of CDI testing. In total, 15.6%
      of 108,092 patients admitted were tested for CDI. Among patients tested, 6.1% had
      positive results. The mean number of tests performed per 1000 admissions by EIA
      and PCR was 257.4 and 162.6, respectively. A total of 8.2% of PCR tests were
      positive compared to 5.0% of EIA tests (P < 0.001). The number of tests performed
      has decreased and the proportion of positive tests increased since PCR
      introduction. CDI incidence has remained constant. Only albumin (3.09 vs 3.24 g
      dl(-1), P 0.002) and inflammatory bowel disease (2.6 vs 7.0%, P < 0.001) status
      differed between the EIA and PCR groups. While hospital mortality did not differ,
      patients diagnosed by PCR had a shorter median length of stay (10 vs 8 days, P
      0.004). Since PCR testing began, less CDI tests have been performed, but the
      proportion of positive results has increased. The incidence of CDI has remained
      constant, suggesting no change in disease epidemiology. The length of stay was
      shorter in the PCR group, reflective of either earlier detection and quicker
      onset of therapy or detection of less severe disease. Mortality did not change
      since the introduction of PCR.

PMID- 26297375
TI  - Molecular pathomechanisms and cell-type-specific disease phenotypes of MELAS
      caused by mutant mitochondrial tRNA(Trp).
AB  - INTRODUCTION: Numerous pathogenic mutations responsible for mitochondrial
      diseases have been identified in mitochondrial DNA (mtDNA)-encoded tRNA genes. In
      most cases, however, the detailed molecular pathomechanisms and cellular
      pathophysiology of these mtDNA mutations -how such genetic defects determine the
      variation and the severity of clinical symptoms in affected individuals- remain
      unclear. To investigate the molecular pathomechanisms and to realize in vitro
      recapitulation of mitochondrial diseases, intracellular mutant mtDNA proportions
      must always be considered. RESULTS: We found a disease-causative mutation,
      m.5541C>T heteroplasmy in MT-TW gene, in a patient exhibiting mitochondrial
      myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) with
      multiple organ involvement. We identified the intrinsic molecular pathomechanisms
      of m.5541C>T. This mutation firstly disturbed the translation machinery of
      mitochondrial tRNA(Trp) and induced mitochondrial respiratory dysfunction,
      followed by severely injured mitochondrial homeostasis. We also demonstrated cell
      type-specific disease phenotypes using patient-derived induced pluripotent stem
      cells (iPSCs) carrying ~100 % mutant m.5541C>T. Significant loss of terminally
      differentiated iPSC-derived neurons, but not their stem/progenitor cells, was
      detected most likely due to serious mitochondrial dysfunction triggered by
      m.5541C>T; in contrast, m.5541C>T did not apparently affect skeletal muscle
      development. CONCLUSIONS: Our iPSC-based disease models would be widely available
      for understanding the "definite" genotype-phenotype relationship of affected
      tissues and organs in various mitochondrial diseases caused by heteroplasmic
      mtDNA mutations, as well as for further drug discovery applications.

PMID- 26297377
TI  - Tweeting From Left to Right: Is Online Political Communication More Than an Echo
      Chamber?
AB  - We estimated ideological preferences of 3.8 million Twitter users and, using a
      data set of nearly 150 million tweets concerning 12 political and nonpolitical
      issues, explored whether online communication resembles an "echo chamber" (as a
      result of selective exposure and ideological segregation) or a "national
      conversation." We observed that information was exchanged primarily among
      individuals with similar ideological preferences in the case of political issues
      (e.g., 2012 presidential election, 2013 government shutdown) but not many other
      current events (e.g., 2013 Boston Marathon bombing, 2014 Super Bowl). Discussion
      of the Newtown shootings in 2012 reflected a dynamic process, beginning as a
      national conversation before transforming into a polarized exchange. With respect
      to both political and nonpolitical issues, liberals were more likely than
      conservatives to engage in cross-ideological dissemination; this is an important
      asymmetry with respect to the structure of communication that is consistent with
      psychological theory and research bearing on ideological differences in
      epistemic, existential, and relational motivation. Overall, we conclude that
      previous work may have overestimated the degree of ideological segregation in
      social-media usage. 

PMID- 26297378
TI  - Bacillus glycinifermentans sp. nov., isolated from fermented soybean paste.
AB  - Two independent isolates of a Gram-stain-positive, facultatively anaerobic,
      motile, rod-shaped bacterium were recovered from cheonggukjang, a Korean
      fermented soybean paste food product. Preliminary sequencing analysis of the 16S
      rRNA gene indicated that these strains were related most closely to Bacillus
      sonorensis KCTC-13918T and Bacillus licheniformis DSM 13T. In phenotypic
      characterization, the novel strains were found to grow between 15 and 55  degrees
      C and to tolerate up to 8 % (w/v) NaCl. Furthermore, the strains grew in media of
      pH 5-10 (optimal growth at pH 7.0). The predominant cellular fatty acids were
      anteiso-C15 : 0 and iso-C15 : 0.The isoprenoid quinone was menaquinone 7 (MK-7).
      The cell-wall peptidoglycan contained meso-diaminopimelic acid. The major polar
      lipids were diphosphatidylglycerol, phosphatidylglycerol,
      phosphatidylethanolamine and an unknown glycolipid. Draft genomes of the two
      strains were determined and in silico DNA-DNA hybridizations with their nearest
      neighbour (B. sonorensis KCTC-13918T) revealed 29.9 % relatedness for both
      strains. Phylogenomic analysis of the genomes was conducted with the core genome
      (799 genes) of all strains in the Bacillus subtilis group and the two strains
      formed a distinct monophyletic cluster. In addition, the strains differed from
      the two most closely related species in that they did not metabolize maltose, d
      galactose, d-sorbitol or d-gluconic acid. The DNA G+C content was 45.9 mol%.
      Based upon the consensus of phylogenetic and phenotypic analyses, these strains
      represent a novel species of the genus Bacillus, for which the name Bacillus
      glycinifermentans sp. nov. is proposed. The type strain is GO-13T ( = KACC 18425T
      = NRRL B-65291T). 

PMID- 26297379
TI  - Strengthening the afferent limb of rapid response systems: an educational
      intervention using web-based learning for early recognition and responding to
      deteriorating patients.
AB  - BACKGROUND: The timely recognition and response to patients with clinical
      deteriorations constitute the afferent limb failure of a rapid response system
      (RRS). This area is a persistent problem in acute healthcare settings worldwide.
      In this study, we evaluated the effect of an educational programme on improving
      the nurses' knowledge and performances in recognising and responding to clinical
      deterioration. METHOD: The interactive web-based programme addressed three areas:
      (1) early detection of changes in vital signs; (2) performance of nursing
      assessment and interventions using airway, breathing, circulation, disability and
      expose/examine and (3) reporting clinical deterioration using identity,
      situation, background, assessment and recommendation. Sixty-seven registered
      nurses participated in the randomised control study. The experimental group
      underwent a 3 h programme while the control group received no intervention.
      Pretests and post-tests, a mannequin-based assessment and a multiple-choice
      knowledge questionnaire were conducted. We evaluated the participants'
      performances in assessing, managing and reporting the deterioration of a patient
      using a validated performance tool. RESULTS: A significantly higher number of
      nurses from the experimental group than the control group monitored respiratory
      rates (48.2% vs 25%, p<0.05) and pulse rates (74.3% vs 37.5%, p<0.01) in the
      simulated environment, after the intervention. The post-test mean scores of the
      experimental group was significantly higher than the control group for knowledge
      (21.29 vs 18.28, p<0.001), performance in assessing and managing clinical
      deterioration (25.83 vs 19.50, p<0.001) and reporting clinical deterioration
      (12.83 vs 10.97, p<0.001). CONCLUSIONS: A web-based educational programme
      developed for hospital nurses to strengthen the afferent limb of the RRS
      significantly increased their knowledge and performances in assessing, managing
      and reporting clinical deterioration.

PMID- 26297380
TI  - Phenotype of non-c.907_909delGAG mutations in TOR1A: DYT1 dystonia revisited.
AB  - BACKGROUND: In addition to the most frequent TOR1A/DYT1 mutation
      (c.907_909delGAG), a growing number of TOR1A sequence variants are found in
      dystonia patients. For most, functional characterization has demonstrated
      pathogenicity at different levels, implying that TOR1A genetic testing should not
      be limited to screening for c.907_909delGAG. METHODS: We tested 461 Serbian
      patients with isolated or combined dystonia for changes in the TOR1A gene and
      performed a systematic literature review of the clinical characteristics of
      patients carrying TOR1A mutations other than c.907_909delGAG. RESULTS: One likely
      pathogenic TOR1A mutation (c.385G>A, p.Val129Ile) was detected in an adult-onset
      cervical dystonia patient. This change is in proximity to the previously reported
      p.Glu121Lys mutation and predicted to decrease the stability of TOR1A-encoded
      protein TorsinA. CONCLUSIONS: Our patient and three other reported carriers of
      non-c.907_909delGAG-mutations within the first three exons of TOR1A showed
      similar phenotypes of adult-onset focal or segmental cervical dystonia. This
      observation raises the possibility of genotype-phenotype correlations in DYT1 and
      indicates that the clinical spectrum of this type of dystonia might be broader
      then previous classic descriptions.

PMID- 26297381
TI  - Optical coherence tomography as a tool to evaluate retinal changes in Parkinson's
      disease.
AB  - BACKGROUND: Though Parkinson's disease (PD) is primarily a disease of the basal
      ganglia, recent evidence suggests that PD affects the retina. OBJECTIVE: The
      study was designed to evaluate the thickness of retinal nerve fiber layer (RNFL)
      and thickness and volume of the macula in PD and hence explore the utility of
      optical coherence tomography (OCT) in studying retinal changes in PD. METHODS: A
      prospective, hospital based evaluation of 30 patients with PD and 30 healthy
      controls was carried out. Various parameters such as RNFL, central macular
      thickness (CMT), central and total macular volumes (TMV) and retinal thickness
      were analyzed using OCT. RESULTS: (a) RNFL thickness was not significantly
      different between the patients and controls. A significant negative correlation
      was found between the RNFL thickness in the right nasal superior sector and the
      UPDRS motor score. (b) CMT was found to be significantly reduced in the right eye
      and a negative correlation with the UPDRS motor score was noted. (c) TMV was
      significantly greater in patients compared to the controls. (d) The outer retinal
      layer in the right nasal quadrant and the right inferior quadrants were found to
      be significantly thinner in patients with PD. CONCLUSIONS: We did not find any
      significant abnormality in the RNFL thickness in patients with PD. Decreased CMT
      in patients with PD and a significant negative correlation of RNFL thickness and
      CMT with severity of PD suggest a remote possibility of dopaminergic depletion in
      the retina. However long term studies are warranted to validate our findings.

PMID- 26297382
TI  - Competing risks model in screening for preeclampsia by maternal factors and
      biomarkers at 11-13 weeks gestation.
AB  - BACKGROUND: Preeclampsia affects approximately 3% of all pregnancies and is a
      major cause of maternal and perinatal morbidity and death. In the last decade,
      extensive research has been devoted to early screening for preeclampsia with the
      aim of reducing the prevalence of the disease through pharmacologic intervention
      in the high-risk group starting from the first trimester of pregnancy. OBJECTIVE:
      The purpose of this study was to develop a model for preeclampsia based on
      maternal demographic characteristics and medical history (maternal factors) and
      biomarkers. STUDY DESIGN: The data for this study were derived from prospective
      screening for adverse obstetric outcomes in women who attended for their routine
      first hospital visit at 11-13 weeks gestation in 2 maternity hospitals in
      England. We screened 35,948 singleton pregnancies that included 1058 pregnancies
      (2.9%) that experienced preeclampsia. Bayes theorem was used to combine the a
      priori risk from maternal factors with various combinations of uterine artery
      pulsatility index, mean arterial pressure, serum pregnancy-associated plasma
      protein-A, and placental growth factor multiple of the median values. Five-fold
      cross validation was used to assess the performance of screening for preeclampsia
      that delivered at <37 weeks gestation (preterm-preeclampsia) and >=37 weeks
      gestation (term-preeclampsia) by models that combined maternal factors with
      individual biomarkers and their combination with screening by maternal factors
      alone. RESULTS: In pregnancies that experienced preeclampsia, the values of
      uterine artery pulsatility index and mean arterial pressure were increased, and
      the values of serum pregnancy-associated plasma protein-A and placental growth
      factor were decreased. For all biomarkers, the deviation from normal was greater
      for early than late preeclampsia; therefore, the performance of screening was
      related inversely to the gestational age at which delivery became necessary for
      maternal and/or fetal indications. Combined screening by maternal factors,
      uterine artery pulsatility index, mean arterial pressure, and placental growth
      factor predicted 75% (95% confidence interval, 70-80%) of preterm-preeclampsia
      and 47% (95% confidence interval, 44-51%) of term-preeclampsia, at a false
      positive rate of 10%; inclusion of pregnancy-associated plasma protein-A did not
      improve the performance of screening. Such detection rates are superior to the
      respective values of 49% (95% confidence interval, 43-55%) and 38% (34-41%) that
      were achieved by screening with maternal factors alone. CONCLUSION: Combination
      of maternal factors and biomarkers provides effective first-trimester screening
      for preterm-preeclampsia.

PMID- 26297383
TI  - Pseudoxanthomonas sangjuensis sp. nov., isolated from greenhouse soil.
AB  - One bacterial strain, designated 5GH38-5(T), which was characterized as aerobic,
      Gram-staining-negative, non-flagellated rods, was isolated from a soil sample
      from a greenhouse in Sangju region, Republic of Korea. It grew at temperatures of
      15-45  degrees C, pH 5.0-9.0 and NaCl concentrations (w/v) of 0-3.0%. 16S rRNA
      gene sequence analysis showed the strain was closely related to Pseudoxanthomonas
      kaohsiungensis J36(T) (97.3%), Pseudoxanthomonas suwonensis 4M1(T) (96.8%),
      Pseudoxanthomonas daejeonensis TR6-08(T) (96.7%) and Pseudoxanthomonas kalamensis
      JA40(T) (96.7%). Its major fatty acids were iso-C16 : 0, anteiso-C15 : 0 and iso
      C15 : 0. The predominant ubiquinone was Q-8. The major polar lipids consisted of
      phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. The
      DNA G+C content was 71.1 mol%. The DNA-DNA hybridization value between strain
      5GH38-5(T) and P. kaohsiungensis J36(T) was less than 70%. The combined
      phenotypic, chemotaxonomic and phylogenetic data showed that strain 5GH38-5(T)
      could be clearly distinguished from closely related members of the genus
      Pseudoxanthomonas. Therefore, the results of this study indicated the existence
      of a novel species of the genus Pseudoxanthomonas, for which we propose the name
      Pseudoxanthomonas sangjuensis sp. nov., with strain 5GH38-5(T) ( = KACC 16961(T)=
      DSM 28345(T)= JCM 19948(T)) as the type strain.

PMID- 26297384
TI  - Functional selectivity of kappa opioid receptor agonists in peripheral sensory
      neurons.
AB  - Activation of kappa opioid receptors (KORs) expressed by peripheral sensory
      neurons that respond to noxious stimuli (nociceptors) can reduce
      neurotransmission of pain stimuli from the periphery to the central nervous
      system. We have previously shown that the antinociception dose-response curve for
      peripherally restricted doses of the KOR agonist (-)-(trans)-3,4-dichloro-N
      methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide (U50488) has an inverted
      U shape. Here, we found that the downward phase of the U50488 dose-response curve
      was blocked by an inhibitor of extracellular signal-regulated kinase (ERK)
      activation U0126. Local administration of the selective KOR agonist salvinorin A
      (Sal-A), also resulted in an inverted U-shaped curve; however, the downward phase
      was insensitive to U0126. By contrast, inhibition of c-Jun N-terminal kinase
      (JNK) partially blocked the downward phase of the dose-response curve to Sal-A,
      suggesting a role for JNK. In cultures of peripheral sensory neurons, U50488 and
      Sal-A inhibited adenylyl cyclase activity with similar efficacies; however, their
      ability to activate ERK and JNK differed. Whereas U50488 activated ERK but not
      JNK, Sal-A activated JNK but not ERK. Moreover, although both U50488 and Sal-A
      produced homologous desensitization, desensitization to U50488 was blocked by
      inhibition of ERK activation, whereas desensitization to Sal-A was blocked by
      inhibition of JNK. Substitution of an ethoxymethyl ether for the C2 position
      acetyl group of Sal-A reduced stimulation of JNK, prevented desensitization by
      ethoxymethyl ether for the C2 position acetyl group of Sal-A, and resulted in a
      monotonic antinociception dose-response curve. Collectively, these data
      demonstrate the functional selectivity of KOR ligands for signaling in peripheral
      sensory neurons, which results in differential effects on behavioral responses in
      vivo. 

PMID- 26297386
TI  - Transcranial Magnetic Stimulation: An Automated Procedure to Obtain Coil-specific
      Models for Field Calculations.
AB  - BACKGROUND: Field calculations for transcranial magnetic stimulation (TMS) are
      increasingly implemented online in neuronavigation systems and in more realistic
      offline approaches based on finite-element methods. They are often based on
      simplified and/or non-validated models of the magnetic vector potential of the
      TMS coils. OBJECTIVE: To develop an approach to reconstruct the magnetic vector
      potential based on automated measurements. METHODS: We implemented a setup that
      simultaneously measures the three components of the magnetic field with high
      spatial resolution. This is complemented by a novel approach to determine the
      magnetic vector potential via volume integration of the measured field. RESULTS:
      The integration approach reproduces the vector potential with very good accuracy.
      The vector potential distribution of a standard figure-of-eight shaped coil
      determined with our setup corresponds well with that calculated using a model
      reconstructed from x-ray images. CONCLUSION: The setup can supply validated
      models for existing and newly appearing TMS coils.

PMID- 26297385
TI  - Roles of lignin biosynthesis and regulatory genes in plant development.
AB  - Lignin is an important factor affecting agricultural traits, biofuel production,
      and the pulping industry. Most lignin biosynthesis genes and their regulatory
      genes are expressed mainly in the vascular bundles of stems and leaves,
      preferentially in tissues undergoing lignification. Other genes are poorly
      expressed during normal stages of development, but are strongly induced by
      abiotic or biotic stresses. Some are expressed in non-lignifying tissues such as
      the shoot apical meristem. Alterations in lignin levels affect plant development.
      Suppression of lignin biosynthesis genes causes abnormal phenotypes such as
      collapsed xylem, bending stems, and growth retardation. The loss of expression by
      genes that function early in the lignin biosynthesis pathway results in more
      severe developmental phenotypes when compared with plants that have mutations in
      later genes. Defective lignin deposition is also associated with phenotypes of
      seed shattering or brittle culm. MYB and NAC transcriptional factors function as
      switches, and some homeobox proteins negatively control lignin biosynthesis
      genes. Ectopic deposition caused by overexpression of lignin biosynthesis genes
      or master switch genes induces curly leaf formation and dwarfism.

PMID- 26297388
TI  - Effect of infant surgical orthopedic treatment on facial growth in preadolescent
      children with unilateral and bilateral complete cleft lip and palate.
AB  - OBJECTIVE: To examine the impact of dentofacial infant orthopedic treatment
      (DFIO) on facial growth in preadolescent children with unilateral complete cleft
      lip and palate (UCCLP) and bilateral complete cleft lip and palate (BCCLP).
      METHODS: This is a retrospective study of patients with UCCLP and BCCLP treated
      at a single center. The treatment group had DFIO, and the control group did not
      have DFIO. Regression models were used to compare outcomes between the study and
      control groups. RESULTS: The study sample comprised 81 patients (54 had DFIO and
      27 did not have DFIO). Among those with UCCLP, those who had DFIO had a shorter
      maxillary length (-2.12 mm; P = .04) and shorter lower anterior facial height (
      2.77 mm; P = .04) compared with controls. Among those with BCCLP, there were no
      significant differences between the treatment and control groups. CONCLUSIONS:
      DFIO treatment could result in shorter maxillary length and lower anterior facial
      height in those with UCCLP.

PMID- 26297387
TI  - Bilateral hand transplantation: Functional benefits assessment in five patients
      with a mean follow-up of 7.6 years (range 4-13 years).
AB  - Between January 2000 and July 2009, five adults who had suffered bilateral
      traumatic below-elbow amputations, received bilateral hand-forearm allografts
      performed by the Lyon team. We report the functional benefits achieved over a
      mean follow-up period of 7.6 years (range 4-13 years), up to December 31st, 2013.
      Clinical measurement is hampered by the lack of specific validated assessment
      tools, obliging us to use non-specific standardized evaluation means. Our
      assessment shows that the restoration of motion, strength, and sensibility are
      fair. Functional results (Carroll upper extremity function test, 400-point test,
      Activities of daily living) are good, as well as quality of life evaluation (RAND
      36). Subjective and overall results explored with questionnaires - Disabilities
      of the Arm Shoulder and Hand (DASH), Hand Transplantation Score System (HTSS),
      are very good. Improvement was seen to continue during the first three years, and
      then tend to become stable. Continued efforts should be directed at designing
      comprehensive, condition-specific, reliable outcome measurement tools. Continuous
      monitoring and evaluation of patients is required to assess the long-term risk
      benefit balance. 

PMID- 26297389
TI  - Three-dimensional analysis of hard and soft tissue changes in patients with
      facial asymmetry undergoing 2-jaw surgery.
AB  - OBJECTIVE: We studied 3-dimensionally how hard and soft tissues of patients with
      facial asymmetry were changed by 2-jaw surgery. STUDY DESIGN: Nine patients
      diagnosed with mandibular prognathism and facial asymmetry who underwent 2-jaw
      surgery were enrolled. Three-dimensional (3-D) computed tomographic images taken
      before and after surgery were superimposed by 3-D imaging software. Linear and
      angular measurements of hard and soft tissues were performed and compared before
      and after surgery. RESULTS: Along with improved roll rotations of the hard and
      soft tissues of the facial structures by surgery, both hard and soft tissue
      mentons were moved toward the nonshifted side. Only the hard tissue mentons,
      however, were important for improving the roll rotation of the mandible.
      Variations in the wing of the nose and lip were significant for shaping the
      maxilla. CONCLUSIONS: The 3-D analysis in this study enabled us to understand
      hard and soft tissues quantitatively, thereby providing helpful information for
      treatment planning.

PMID- 26297390
TI  - Demineralized deciduous tooth as a source of bone graft material: its biological
      and physicochemical characteristics.
AB  - OBJECTIVE: To examine structural and physicochemical characteristics of
      demineralized deciduous tooth powder (DDTP) in relation to demineralization time
      and to present potential of using DDTP as a bone graft material. STUDY DESIGN:
      For structural and physicochemical analysis, scanning electron microscopy,
      inductively coupled plasma spectrometry, energy-dispersive X-ray analysis, X-ray
      diffraction analysis, differential scanning calorimetry, and Brunauer-Emmett
      Teller surface area analysis were performed. In in vivo experiments, DDTP was
      grafted in 20 Sprague-Dawley rats' calvarial defects, and radiographic and
      histologic examination and histomorphometric analysis were performed. RESULTS: In
      vitro studies confirmed physicochemical demands for collagen-based bone graft
      material, such as lowered calcium content, lowered crystallinity of
      hydroxyapatite, and exposed organic structures to demineralization. In vivo
      experiment indicated new bone formation in DDTP-grafted sites and gradual
      resorption of the grafted particles. Defect closure rate was significantly higher
      in the 8-week DDTP-grafted group compared with control (P < .05). CONCLUSIONS:
      Deciduous teeth had structural and physicochemical characteristics suitable for
      grafting with appropriate demineralization. Bone healing was observed to have
      successfully occurred in DDTP-grafted sites.

PMID- 26297391
TI  - Current and future options of regeneration methods and reconstructive surgery of
      the facial skeleton.
AB  - Musculoskeletal defects attributable to trauma or infection or as a result of
      oncologic surgery present a common challenge in reconstructive maxillofacial
      surgery. The autologous vascularized bone graft still represents the gold
      standard for salvaging these situations. Preoperative virtual planning offers
      great potential and provides assistance in reconstructive surgery. Nevertheless,
      the applicability of autologous bone transfer might be limited within the
      medically compromised patient or because of the complexity of the defect and the
      required size of the graft to be harvested. The development of alternative
      methods are urgently needed in the field of regenerative medicine to enable the
      regeneration of the original tissue. Since the first demonstration of de novo
      bone formation by regenerative strategies and the application of bone growth
      factors some decades ago, further progress has been achieved by tissue
      engineering, gene transfer, and stem cell application concepts. This review
      summarizes recent approaches and current developments in regenerative medicine. 

PMID- 26297392
TI  - The relationship between the severity of radiation-induced oral mucositis and the
      myeloperoxidase levels in rats.
AB  - OBJECTIVE: Oral mucositis is a common adverse reaction to radiotherapy for head
      and neck cancer, and there are concerns regarding a decreased quality of life in
      patients receiving radiotherapy. The purpose of this study was to investigate the
      relationship between the severity of radiation-induced oral mucositis and the
      myeloperoxidase (MPO) levels in irradiated tissues. STUDY DESIGN: Ninety-six F344
      rats were divided into the following 4 groups: 10-Gy, 18-Gy, and 30-Gy
      irradiation groups, and a nonirradiation group. Oral mucositis was induced by the
      administration of single doses of radiation via exposure. After irradiation, the
      rats were evaluated on the basis of weight measurements, macroscopic findings
      according to a grading scale (Oral Mucositis Index [OMI]), and the results of
      tissue MPO assays. RESULTS: Weights decreased whereas the OMI scores and MPO
      levels increased, depending on the dose of exposure. The Spearman rank
      correlation test showed a significant correlation between the OMI scores and the
      MPO levels in the tissues with a correlation coefficient of 0.824 (P < .01).
      CONCLUSIONS: In this study, the MPO levels in the irradiated tissue were
      increased in the cases involving severe radiation-induced oral mucositis
      evaluated in rats using a grading scale.

PMID- 26297393
TI  - Oral melanocytic nevi: a clinicopathologic study of 100 cases.
AB  - OBJECTIVE: The purpose of this study was to evaluate the clinical and
      histopathologic features of oral melanocytic nevi (OMN). STUDY DESIGN: One
      hundred cases of OMN were retrieved from the files of two oral pathology
      services, and the data were analyzed with regard to histologic type and clinical
      features. RESULTS: Intramucosal nevus was the most common type (61%), followed by
      common blue nevus (23%), compound nevus (7%), and junctional nevus (3%). Combined
      nevus and cellular blue nevus were rare (2% each). The hard palate was the most
      commonly affected site (33%), followed by the buccal mucosa (18%), vermilion
      border of the lip (18%), and gingiva (15%). An interesting case of intramucosal
      nevus with lipomatosus-like changes and neurotization and two cases of oral
      dysplastic nevus are also reported. CONCLUSIONS: Intramucosal and common blue
      nevi are the most common types of OMN. Dysplastic nevus, which is recognized as a
      marker for melanoma in the skin, can rarely involve the oral cavity. Accordingly,
      dentists, especially oral and maxillofacial pathologists, should become familiar
      with the clinical and histopathologic features of this entity.

PMID- 26297394
TI  - Adenoid ameloblastoma: clinicopathologic description of five cases and systematic
      review of the current knowledge.
AB  - OBJECTIVE: To describe the clinicopathologic and immunohistochemical features of
      five cases of adenoid ameloblastoma. STUDY DESIGN: Clinicopathologic data were
      gathered from medical records and compared with those compiled from a systematic
      review. Slides were also immunohistochemically stained for Ki-67, p16, p53, and
      cytokeratins (7, 8, 14, 18, and 19). RESULTS: There were 3 males (60%) and 2
      (40%) females. The mean age was 44 +/- 10 years. Of the five adenoid
      ameloblastomas, 4 (80%) occurred in the posterior maxilla. Patients typically
      complained of asymptomatic swelling. All patients received surgical resection as
      primary therapy; 1 (20%) patient also received adjuvant radiotherapy. Recurrence
      was diagnosed in all patients. Immunohistochemically, the tumors stained focally
      positive for CK7, 8, 14, and 18 and diffusely positive for CK-19, p16, and p53.
      The mean Ki-67-positive cells were 72.4 +/- 24.9 positive cells per high-power
      field (range 53-111). CONCLUSIONS: To our knowledge, this is the largest series
      of adenoid ameloblastoma reported in the literature. Our data suggest that this
      entity demonstrates aggressive behavior characterized by a high likelihood of
      recurrence.

PMID- 26297395
TI  - A systematic review of the literature of nevoid basal cell carcinoma syndrome
      affecting East Asians and North Europeans.
AB  - OBJECTIVE: To compare, by systematic review, North European and East Asian
      consecutive case series of nevoid basal cell carcinoma syndrome (NBCCS). STUDY
      DESIGN: A systematic review of the literature was performed for all consecutive
      case series of NBCCS, which included keratocystic odontgenic tumors (KCOTs)
      arising in North European and East Asian communities. The clinical and
      radiologically apparent features were identified and synthesized, and a meta
      analysis was performed. RESULTS: East Asian reports were significantly more
      "proband only" compared with North European reports. Significant differences
      between these 2 communities were observed for 5 of the 6 major features and 11 of
      the 27 minor features. With regard to the major NBCCS features, the North
      Europeans displayed significantly more frequent basal cell carcinomas, calcified
      falx cerebri, palmar and plantar pits, and a family history, whereas the East
      Asians displayed KCOTs significantly more frequently. With regard to minor
      features, East Asians displayed significantly more frequent cleft lips and
      palates and hypertelorism. CONCLUSIONS: East Asians displayed multiple KCOTs and
      cleft lips and palates more frequently compared with North Europeans.

PMID- 26297396
TI  - A consecutive case series of nevoid basal cell carcinoma syndrome affecting the
      Hong Kong Chinese.
AB  - OBJECTIVES: To identify the clinical and radiologic features of nevoid basal cell
      carcinoma syndrome (NBCCS) in the Hong Kong Chinese, particularly those of
      keratocystic odontogenic tumors (KCOTs), at first presentation at a dental
      hospital. STUDY DESIGN: A consecutive case series of NBCCS was identified in the
      University of Hong Kong Dental Hospital. RESULTS: All 5 Hong Kong NBCCS cases
      presented with symptoms arising from their KCOTs; 3 with swelling, 3 with pain,
      and 2 with nasal discharge. The cases exhibited 4 major features (KCOTs,
      calcified falx cerebri, palmar/plantar pits, and basal cell carcinoma) and 4
      minor features (sella bridges, bossing, hypertelorism, and mandibular
      prognathism). The KCOTs were all unilocular. The tumors displaced teeth in 4
      cases. Only 1 had root resorption. There were 2 nonsyndromic cases with multiple
      KCOTs. CONCLUSIONS: The unilocular presentation of the syndromic KCOTs was
      significantly greater than that of the solitary cases, arising within the same
      community over the same period. The other presenting features of the syndromic
      KCOTs did not differ from the solitary KCOTs. The recurrence rate of syndromic
      KCOTs was significantly greater than of the solitary KCOTs. Nonsyndromic cases
      with multiple KCOTs could be more common in East Asians.

PMID- 26297397
TI  - LBP/BPI homologue in Eisenia andrei earthworms.
AB  - LBP/BPIs are pattern recognition receptors that are often present in vertebrates
      and in invertebrates, and they play a defense role against pathogens. We have
      identified 1698 bp cDNA sequence from the Eisenia andrei earthworm with predicted
      amino acid sequence that shares homology with the LBP/BPI family (EaLBP/BPI).
      Sequence analysis of EaLBP/BPI proved the existence of two conserved domains with
      the potential ability to bind LPS. The predicted molecular mass of the EaLBP/BPI
      protein is 53.5 kDa, and its high basicity (pI 9.8) is caused by its high
      arginine content. Constitutive transcription of the Ealbp/bpi gene was shown in
      all tested tissues, with the highest level in coelomocytes and seminal vesicles;
      the lowest level was detected in the intestine. On the contrary, another
      earthworm LPS-binding molecule CCF (coelomic cytolytic factor) was expressed only
      in the intestine and coelomocytes. In E. andrei coelomocytes, the transcription
      of Ealbp/bpi gene was up-regulated in response to bacterial stimulation, reaching
      a maximum at 8 and 16 h post stimulation with Bacillus subtilis and Escherichia
      coli, respectively. 

PMID- 26297398
TI  - Low multiple electrode aggregometry platelet responses are not associated with
      non-synonymous variants in G-protein coupled receptor genes.
AB  - INTRODUCTION: Multiple electrode aggregometry (MEA) improves prediction of
      thrombosis and bleeding in cardiac patients. However, the causes of inter
      individual variation in MEA results are incompletely understood. We explore
      whether low MEA results are associated with platelet G-protein coupled receptor
      (GPCR) gene variants. METHODS: The effects of P2Y12 receptor (P2Y12), thromboxane
      A2 receptor (TPalpha) and protease-activated receptor 1 (PAR1) dysfunction on the
      MEA ADP-test, ASPI-test and TRAP-test were determined using receptor antagonists.
      Cardiac surgery patients with pre-operative MEA results suggesting GPCR
      dysfunction were selected for P2Y12 (P2RY12), TPalpha (TBXA2R) and PAR1 (F2R)
      sequencing. RESULTS: In control blood samples, P2Y12, TPalpha or PAR1 antagonists
      markedly reduced ADP-test, ASPI-test and TRAP-test results respectively. In the
      636 patients from a cohort of 2388 cardiac surgery patients who were not
      receiving aspirin or a P2Y12 blocker, the median ADP-test result was 75.1 U
      (range 4.8-153.2), ASPI-test 83.7 U (1.4-157.3) and TRAP-test 117.7 U (2.4
      194.1), indicating a broad range of results unexplained by anti-platelet drugs.
      In 238 consenting patients with unexplained low MEA results, three P2RY12
      variants occurred in 70/107 (65%) with suspected P2Y12 dysfunction and four
      TBXA2R variants occurred in 19/22 (86%) with suspected TPalpha dysfunction
      although the later group was too small to draw meaningful conclusions about
      variant frequency. All the variants were synonymous and unlikely to cause GPCR
      dysfunction. There were no F2R variants in the 109 cases with suspected PAR1
      dysfunction. CONCLUSION: MEA results suggesting isolated platelet GPCR
      dysfunction were common in cardiac surgery patients, but were not associated with
      non-synonymous variants in P2RY12 or F2R.

PMID- 26297399
TI  - Clinical Approach to Advanced Renal Function Testing in Dogs and Cats.
AB  - Serum creatinine concentration is insensitive for detecting kidney injury and
      does not assist in differentiation between glomerular versus tubular damage.
      Advanced renal function tests, including glomerular filtration rate testing,
      determining fractional excretion of electrolytes, and assay of urine biomarkers,
      may allow earlier detection of reduced renal function mass, differentiation of
      renal from non-renal causes of azotemia, and assist with localization of damage.
      This article reviews the principles, indications, and limitations of these tests
      and describes their use in sample clinical scenarios. 

PMID- 26297400
TI  - A Laboratory Diagnostic Approach to Hepatobiliary Disease in Small Animals.
AB  - Routine biochemical tests generally include serum enzymes, proteins, and other
      markers useful for identifying hepatobiliary disease in dogs and cats. Obtaining
      results outside the reference intervals can occur with direct hepatocellular
      injury, enzyme induction by hepatocytes or biliary epithelium, or decreased
      hepatic function. However, detection of biochemical abnormalities does not
      necessarily indicate clinically significant disease. For a comprehensive approach
      to detection and treatment of hepatobiliary disease, the laboratory results must
      be correlated with the history and physical examination findings, diagnostic
      imaging results, and other assays. 

PMID- 26297401
TI  - Diagnosis of Small Intestinal Disorders in Dogs and Cats.
AB  - Laboratory tests are an important part of the workup of small intestinal diseases
      in dogs and cats. Especially in chronic cases, when extragastrointestinal causes
      need to be ruled out, it is important to adhere to a systematic workup. This
      article details the newest available data on tests to aid this diagnostic
      process. Once the diagnosis of a chronic enteropathy is made, there are many
      laboratory tests that can help in monitoring the disease and providing prognostic
      information. Several new tests being evaluated for clinical usefulness are
      discussed. 

PMID- 26297402
TI  - Practical Interpretation and Application of Exocrine Pancreatic Testing in Small
      Animals.
AB  - The pancreas remains a difficult organ to evaluate using laboratory methods
      alone. No single laboratory test is diagnostic of pancreatitis (chronic or acute)
      without other diagnostic modalities concurring with the diagnosis or ruling out
      other diseases. The diagnosis of pancreatitis is particularly difficult in cats,
      and pancreatitis often occurs with other diseases. The use of pancreatic cytology
      may be useful in diagnosing both inflammation and neoplasia. Exocrine pancreatic
      insufficiency (EPI) can be relatively easily diagnosed when clinically manifested
      by the measurement of trypsinlike immunoreactivity. Diagnosis is more difficult
      when EPI is subclinical. 

PMID- 26297403
TI  - Using Cardiac Biomarkers in Veterinary Practice.
AB  - Blood-based assays for various cardiac biomarkers can assist in the diagnosis of
      heart disease in dogs and cats. The two most common markers are cardiac troponin
      I and N-terminal pro-B-type natriuretic peptide. Biomarker assays can assist in
      differentiating cardiac from noncardiac causes of respiratory signs and detection
      of preclinical cardiomyopathy. Increasingly, studies indicate that cardiac
      biomarker testing can help assess the risk of morbidity and mortality in animals
      with heart disease. Usage of cardiac biomarker testing in clinical practice
      relies on proper patient selection, correct interpretation of test results, and
      incorporation of biomarker testing into existing diagnostic methods. 

PMID- 26297404
TI  - Use of Lactate in Small Animal Clinical Practice.
AB  - Lactate is a product of anaerobic metabolism. Lactate concentration in blood is
      used clinically as an indicator of tissue hypoperfusion and hypoxia to determine
      disease severity, assess response to therapy, and predict outcome. This article
      reviews lactate physiology, sample collection and processing, and interpretation
      of lactate concentration in clinical practice. 

PMID- 26297405
TI  - Diagnosis of Disorders of Iron Metabolism in Dogs and Cats.
AB  - Iron is an essential element and is used by every cell in the body. This article
      summarizes iron metabolism and disorders associated with iron metabolism in dogs
      and cats. The diagnostic tests currently in use for assessing iron status are
      discussed. 

PMID- 26297406
TI  - Making Sense of Lymphoma Diagnostics in Small Animal Patients.
AB  - This article summarizes and compares the various assays available to aid in the
      diagnosis and characterization of lymphoma in small animal patients. These
      techniques include cytology, histopathology, immunocytochemistry and
      immunohistochemistry, immunophenotyping by flow cytometry, and polymerase chain
      reaction for clonal antigen receptor gene rearrangement. 

PMID- 26297407
TI  - Hematology of the Domestic Ferret (Mustela putorius furo).
AB  - Pet ferrets are presented to veterinary clinics for routine care and treatment of
      clinical diseases and female reproductive problems. In addition to obtaining
      clinical history, additional diagnostic testing may be required, including
      hematological assessments. This article describes common blood collection
      methods, including venipuncture sites, volume of blood that can be safely
      collected, and handling of the blood. Hematological parameters for normal ferrets
      are provided along with a description of the morphology of ferret leukocytes to
      assist in performing a differential count. 

PMID- 26297408
TI  - Hematological Assessment in Pet Rabbits: Blood Sample Collection and Blood Cell
      Identification.
AB  - Pet rabbits are presented to veterinary clinics for routine care and treatment of
      clinical diseases. In addition to obtaining clinical history, additional
      diagnostic testing may be required, including hematological assessments. This
      article describes common blood collection methods, including venipuncture sites,
      volume of blood that can be safely collected, and handling of the blood.
      Hematological parameters for normal rabbits are provided for comparison with in
      house or commercial test results. A description of the morphology of rabbit
      leukocytes is provided to assist in performing a differential count. Differential
      diagnoses are provided for abnormal values identified in the hemogram. 

PMID- 26297409
TI  - Hematologic Assessment in Pet Rats, Mice, Hamsters, and Gerbils: Blood Sample
      Collection and Blood Cell Identification.
AB  - Hamsters, gerbils, rats, and mice are presented to veterinary clinics and
      hospitals for prophylactic care and treatment of clinical signs of disease.
      Physical examination, history, and husbandry practice information can be
      supplemented greatly by assessment of hematologic parameters. As a resource for
      veterinarians and their technicians, this article describes the methods for
      collection of blood, identification of blood cells, and interpretation of the
      hemogram in mice, rats, gerbils, and hamsters. 

PMID- 26297410
TI  - Hematological Assessment in Pet Guinea Pigs (Cavia porcellus): Blood Sample
      Collection and Blood Cell Identification.
AB  - Pet guinea pigs are presented to veterinary clinics for routine care and
      treatment of clinical diseases. In addition to obtaining clinical history and
      exam findings, diagnostic testing may be required, including hematological
      assessments. This article describes common blood collection methods, including
      venipuncture sites, the volume of blood that can be safely collected, and
      handling of the blood. Hematological parameters for normal guinea pigs are
      provided for comparison with in-house or commercial test results. A description
      of the morphology of guinea pig leukocytes is provided to assist in performing a
      differential count. 

PMID- 26297411
TI  - Avian Hematology.
AB  - Avian veterinarians often rely heavily on the results of various diagnostic
      tests, including hematology results. As such, cellular identification and
      evaluation of the cellular response are invaluable tools that help veterinarians
      understand the health or condition of their patient, as well as to monitor
      severity and clinical progression of disease and response to treatment.
      Therefore, it is important to thoroughly understand how to identify and evaluate
      changes in the avian erythron and leukon, as well as to interpret normal and
      abnormal results. 

PMID- 26297412
TI  - Reptile Hematology.
AB  - The basic principles of hematology used in mammalian medicine can be applied to
      reptiles. The appearances of the blood cells are significantly different from
      those seen in most mammals, and vary with taxa and staining method used. Many
      causes for abnormalities of the reptilian hemogram are similar to those for
      mammals, although additional factors such as venipuncture site, season,
      hibernation status, captivity status, and environmental factors can also affect
      values, making interpretation of hematologic results challenging. Values in an
      individual should be compared with reference ranges specific to that species,
      gender, and environmental conditions when available. 

PMID- 26297413
TI  - Fish Hematology and Associated Disorders.
AB  - Fish health is a growing concern as pets, education, and aquaculture evolves. For
      the veterinary staff, fish handling, diagnostics, medicine, and surgery may
      require specialized training and equipment in comparison with terrestrial and
      arboreal animals, simply because of their aquatic nature and diversity. Fish
      hematology is one diagnostic tool that may not require additional equipment, may
      be inexpensive, and provide useful information in guiding treatment options.
      Challenges involving hematology may include handling and restraint, venipuncture,
      evaluation, and interpretation. In this article, strategies for these challenges
      are discussed for teleost (bony fish) and elasmobranch (cartilaginous fish) fish
      types. 

PMID- 26297414
TI  - Evaluation of the Blood Film.
AB  - Evaluation of hemic cell morphology in stained blood film may be the most
      important part of the hematologic evaluation of exotic animals. The blood film
      provides important information regarding red blood cell abnormalities, such as
      changes in cell shape and color, presence of inclusions, and, in the case of
      lower vertebrates, changes in the position of the cell nucleus. Stained blood
      film also provides information about changes in leukocyte numbers and morphology,
      and shows important hemic features of mammalian platelets and the thrombocytes of
      lower vertebrates. The blood film is needed in the detection and identification
      of blood parasites. 

PMID- 26297415
TI  - A new inventory for middle east dust source points.
AB  - We use the Moderate Resolution Imaging Spectroradiometer (MODIS) sensor on both
      Terra and Aqua satellites to present new high-resolution mapping of major
      atmospheric dust source points in the Middle East region on the basis of the
      improved version of the recently developed Middle East Dust Index (MEDI) applied
      to 70 dust storms, which occurred during the period between 2001 and 2012.
      Results indicate that 247 different source points have participated in dust storm
      generation in the Middle East region in which Iraq and Syria are the highest
      efficient sites for dust storm generation in this region, respectively. Using
      extracted indices for Deep Blue algorithm, identified dust sources were
      classified into three levels of intensity. The frequency of occurrence approach,
      the relationship between high atmospheric dust content and its number of
      occurrences, is also used to identify sensitive source points. High-intensity
      dust storms are mainly located west of Iraq and the border of Iraq and Syria. We
      will discuss the implications of our results in understanding the global dust
      cycle. 

PMID- 26297416
TI  - Assessment of elemental and NROM/TENORM hazard potential from non-nuclear
      industries in North Sinai, Egypt.
AB  - Non-nuclear industries use raw materials containing significant levels of
      naturally occurring radioactive material (NORM). The processing of these
      materials may expose workers engaged in or even people living near such sites to
      technologically enhanced naturally occurring radioactive material (TENORM) above
      the natural background. Inductively coupled plasma and gamma ray spectrometry
      have been used to determine major and trace elements and radionuclide
      concentrations in various samples, respectively, in order to investigate the
      environmental impact of coal mining and cement plant in North Sinai, Egypt.
      Generally, very little attention was directed to the large volumes of waste
      generated by either type of industrial activities. Different samples were
      analyzed including various raw materials, coal, charcoal, Portland and white
      cement, sludge, and wastes. Coal mine and cement plant workers dealing with waste
      and kaolin, respectively, are subjected to a relatively high annual effective
      dose. One of the important finding is the enhancement of all measured elements
      and radionuclides in the sludge found in coal mine. It may pose an environmental
      threat because of its large volume and its use as combustion material. The mine
      environment may have constituted Al, Fe, Cr, and V pollution source for the local
      area. Higher concentration of Al, Fe, Mn, B, Co, Cr, Mn, Ni, Sr, V, and TENORM
      were found in Portland cement and Zn in white cement. Coal has higher
      concentrations of Al, Fe, B, Co, Cr, and V as well as (226)Ra and (232)Th. The
      compiled results from the present study and different worldwide investigations
      demonstrate the obvious unrealistic ranges normally used for (226)Ra and (232)Th
      activity concentrations in coal and provided ranges for coal, Portland and white
      cement, gypsum, and limestone. 

PMID- 26297418
TI  - Reconstruction using 'triangular approximation' of bone grafts for orbital
      blowout fractures.
AB  - There are many orbital wall reconstruction materials that can be used in surgery
      for orbital blowout fractures. We consider autogenous bone grafts to have the
      best overall characteristics among these materials and use thinned, inner
      cortical tables of the ilium. A bone bender is normally used to shape the inner
      iliac table to match the orbital shape. Since orbital walls curve three
      dimensionally, processing of bone grafts is not easy and often requires much time
      and effort. We applied a triangular approximation method to the processing of
      bone grafts. Triangular approximation is a concept used in computer graphics for
      polygon processing. In this method, the shape of an object is represented as
      combinations of polygons, mainly triangles. In this study, the inner iliac table
      was used as a bone graft, and cuts or scores were made to create triangular
      sections. These triangular sections were designed three-dimensionally so that the
      shape of the resulting graft approximated to the three-dimensional orbital shape.
      This method was used in 12 patients with orbital blowout fractures, which
      included orbital floor fractures, medial wall fractures, and combined inferior
      and medial wall fractures. In all patients, bone grafts conformed to the orbital
      shape and good results were obtained. This simple method uses a reasonable and
      easy-to-understand approach and is useful in the treatment of bone defects in
      orbital blowout fractures when using a hard graft material. 

PMID- 26297419
TI  - Biomechanical evaluation of different angle-stable locking plate systems for
      mandibular surgery.
AB  - PURPOSE: To compare the initial stability and stability after fatigue of three
      different locking systems (Synthes((r)), Stryker((r)) and Medartis((r))) for
      mandibular fixation and reconstruction. METHOD: Standard mandible locking plates
      with identical profile height (1,5 mm), comparable length and screws with
      identical diameter (2,0 mm) were used. Plates were fixed with six screws
      according a preparation protocol. Four point bending tests were then performed
      using artificial bone material to compare their initial stability and failure
      limit under realistic loading conditions. Loading of the plates was performed
      using of a servo hydraulic driven testing machine. The stiffness of the
      implant/bone construct was calculated using a linear regression on the
      experimental data included in a range of applied moment between 2 Nm and 6 Nm.
      RESULTS: No statistical difference in the elastic stiffness was visible between
      the three types of plate. However, differences were observed between the systems
      concerning the maximal load supported. The Stryker and Synthes systems were able
      to support a significantly higher moment. CONCLUSION: For clinical application
      all systems show good and reliable results. Practical aspects such as handling,
      possible angulation of screw fixation, possibility of screw/plate removal, etc.
      may favour one or the other plating system.

PMID- 26297420
TI  - Guided implant surgery after free-flap reconstruction: Four-year results from a
      prospective clinical trial.
AB  - AIM: The aim of this prospective clinical study is to assess the 4-year outcomes
      of implant-supported restorations performed using a computer-guided template
      assisted flapless implant surgery approach in patients reconstructed with fibula
      or iliac crest free flaps. MATERIALS AND METHODS: Twelve jaws in 10 patients were
      reconstructed with osteomyocutaneous free flap after tumour resection or gunshot
      wound, after complete healing computer-assisted template-based flapless implant
      placement, based on prosthetic and aesthetic analysis, was performed using a
      customized protocol. Treatment success was evaluated using the following
      parameters: survival of implants/prostheses, prosthetic and biologic
      complications, marginal bone remodelling, soft tissue parameters and patient
      satisfaction. RESULTS: A total of 56 implants were placed; the implants ranged
      between 8 and 16 mm in length and were either 3.5, 4.3 or 5 mm wide. All the
      patients have reached the 4-year follow-up. Three implants were lost accounting
      for an overall implant survival rate of 94.6%. No prosthesis were lost. Some
      complications were recorded. Four years after loading the mean marginal bone loss
      was 1.43 +/- 0.49 mm at the palatal/lingual site and 1.48 +/- 0.46 mm at the
      vestibular site. All the patients showed healthy soft tissues with stable probing
      depth (4 .93 +/- 0.75%) and successful bleeding on probing values (12 +/- 5.8%);
      90% of patients were satisfied of the treatment at the 4-year follow-up.
      CONCLUSIONS: Computer-guided template-assisted flapless implant surgery seems to
      be a viable option for patients undergoing reconstruction with free flaps after
      tumour resection or gunshot trauma, although many challenges remain. A high
      degree of patient satisfactorily was reported.

PMID- 26297421
TI  - Evaluation of prebent miniplates in fixation of Le Fort I advancement osteotomy
      with the finite element method.
AB  - The stability of segments after Le Fort I osteotomy first attracted the
      researcher's interest when the surgical concept was conceived. Prebent plates are
      the ultimate modification of plate systems in craniofacial surgery; they have two
      right angles and are available in different lengths for use in maxillary
      advancement surgery. For this research, cone-beam computed tomography (CBCT)
      images of a male patient were obtained and scanned, and a 3D maxillary bone was
      created. Conventional Le Fort I osteotomies with 5 and 10 mm advancements were
      performed on both the cortical and trabecular bone using the Surgical Simulation
      Module of Mimics software; 1.7 mm Leibinger standard orthognathic 5-hole L plates
      and 1.7 mm Leibinger orthognathic advancement 11-hole prebent plates were adapted
      to the fragments. Displacement of the segment, the von Mises (VM) stresses (on
      the titanium miniplates) and the maximum principal (MP) stresses (on the bone)
      were evaluated for each configuration. Prebent plates offer a good alternative to
      the conventional two plate system, except in operations where maxillary
      advancement exceeds 5 mm. Surgical procedures that include advancement exceeding
      5 mm or vertical position changes remain controversial and further studies are
      needed.

PMID- 26297422
TI  - Endoscopic management of salivary gland obstructive diseases in patients with
      Sjogren's syndrome.
AB  - PURPOSE: To evaluate, on the basis of our clinical experience, the reliability of
      an endoscopic approach to the management of obstructive salivary diseases related
      to Sjogren's syndrome. MATERIAL AND METHODS: A retrospective review of all
      patients affected by Sjogren's syndrome who were followed up at the Maxillo
      Facial Unit of the Second University of Naples Hospital and referred from the
      Reumatology Unit of the same hospital from September 2007 to July 2012 for
      chronic obstructive sialadenitis unresponsive to medical therapy. A total of 34
      patients (29 women and 5 men) were recruited for this study. After the detection
      of the impaired gland, under local anesthesia with lidocaine 2% to the orifice
      region and a gradual dilation of the duct orifice, the diagnostic unit was
      introduced into the duct and was advanced forward until reaching the ductal
      system, with continuous lavage with isotonic saline solution. The plaques were
      washed out, and any strictures were dilated. Mucus plugs and debris were removed
      with irrigation or with a forceps if necessary. RESULTS: Our cohort included 34
      patients with a mean age of 51.76 years. A total of 60 parotid glands and 25
      submandibular glands were explored and treated. Strictures were found in 38
      glands (38 of 85; 45%), mucus plugs in 47 glands (47 of 85; 55%), mucus plugs and
      strictures together in three glands (3 of 85; 4%), and kinks in two glands (2 of
      85; 2%). In 32 parotid glands (32 of 60; 53%) the Stensen duct was affected, in
      two (2 of 60; 3%) only secondary ducts, and in 18 (18 of 60; 30%) both. In
      submandibular glands explored, strictures and mucus plugs were mainly observed in
      Wharton ducts. Symptomatic improvement was achieved in 29 patients (29 of 34;
      85%), in a follow-up period ranging from 5 months to 3 years. CONCLUSIONS:
      Interventional sialoendoscopy is a viable technique to treat acute symptomatology
      in patients with obstructive salivary gland diseases related to Sjogren's
      syndrome and refractory to conventional management.

PMID- 26297424
TI  - Metamorphic changes in abdominal spines of Forcipomyia nigra pupae (Diptera:
      Ceratopogonidae).
AB  - Pupae of Forcipomyia nigra biting midges bear double rows of dorsal and lateral
      spines. Their arrangement corresponds to the distribution of larval
      mechanosensory setae. They are serrated simple cuticular structures with
      tubercles but, in contrast to larval secretory mechanoreceptors, they are not
      innervated and do not exhibit any pores. The ultrastructure of abdominal spines
      varies among different pupal stages. They are produced by epidermal cells which
      fill the interior of the spine. In the youngest pupae epidermal cells are tightly
      packed and adhere to the cuticle. Then, the cells withdraw from the spinal cavity
      and the beginning of autophagy is observed. The last stage represents abdominal
      spines without any cellular material and then apoptosis probably proceeds in the
      withdrawn epidermal cells. Since the pupal spines occupied the same region of the
      segment as the larval setae, we consider that the same genes are responsible for
      their formation as for the formation of epidermal cells but that their
      mechanosensory and secretory function is no longer needed. 

PMID- 26297423
TI  - Application of fossa bone graft to stabilize stock total joint prosthesis in
      temporomandibular joint surgery.
AB  - PURPOSE: To describe a new glenoid fossa bone graft technique, and to evaluate
      its effect on the stability of stock fossa prosthesis implantation in total
      alloplastic joint replacement surgery. METHODS: Eight patients who underwent
      total joint replacement surgery with a Biomet stock prosthesis (Biomet, Warsaw,
      IN, USA) from November 2013 to April 2014 were included in this study. ProPlan
      CMF 1.4 software (Materialise NV, Leuven, Belgium) was used to choose the
      prosthesis size and place it in the right position. The depth of the fossa was
      measured, and the osteotomy line was designed to cut the bone which overlapped
      the fossa prosthesis. A bone graft, taken from the bottom of the articular
      eminence or the condylar neck, was used to fill in the fossa and make a flat
      plane in combination with the residual eminence for the positioning of the fossa
      prosthesis. The stability of the fossa prosthesis was evaluated both intra
      operatively and postoperatively with computed tomography (CT) scanning after at
      least 6 months of follow-up. The bone contact area of the fossa prosthesis and
      the volume of the grafted bone were measured. RESULTS: Fossa prostheses were
      intra-operatively stable after bone grafting. All patients had stable occlusion
      after surgery and at follow-up. Postoperative measurement showed that the bone
      contact area with the fossa prosthesis increased from 52.8% to 88.5% after bone
      grafting. Postoperative CT measurements (at an average of 9 months after surgery)
      showed that the bone graft volume decreased by 11.1%. CONCLUSION: Bone grafts in
      the glenoid fossa help to improve the stability of Biomet stock fossa prosthesis
      implantation.

PMID- 26297426
TI  - Commentary to 'Post-surgical infections and perioperative antibiotics usage in
      pediatric genitourinary procedures'.

PMID- 26297425
TI  - Mas receptor deficiency exacerbates lipopolysaccharide-induced cerebral and
      systemic inflammation in mice.
AB  - Beyond the classical actions of the renin-angiotensin system on the regulation of
      cardiovascular homeostasis, several studies have shown its involvement in acute
      and chronic inflammation. The G protein-coupled receptor Mas is a functional
      binding site for the angiotensin-(1-7); however, its role in the immune system
      has not been fully elucidated. In this study, we evaluated the effect of genetic
      deletion of Mas receptor in lipopolysaccharide (LPS)-induced systemic and
      cerebral inflammation in mice. Inflammatory response was triggered in Mas
      deficient (Mas(-/-)) and C57BL/6 wild-type (WT) mice (8-12 weeks-old) by
      intraperitoneal injection of LPS (5 mg/kg). Mas(-/-) mice presented more intense
      hypothermia compared to WT mice 24 h after LPS injection. Systemically, the bone
      marrow of Mas(-/-) mice contained a lower number of neutrophils and monocytes 3 h
      and 24 h after LPS injection, respectively. The plasma levels of inflammatory
      mediators KC, MCP-1 and IL-10 were higher in Mas(-/-) mice 24 h after LPS
      injection in comparison to WT. In the brain, Mas(-/-) animals had a significant
      increase in the number of adherent leukocytes to the brain microvasculature
      compared to WT mice, as well as, increased number of monocytes and neutrophils
      recruited to the pia-mater. The elevated number of adherent leukocytes on brain
      microvasculature in Mas(-/-) mice was associated with increased expression of
      CD11b - the alpha-subunit of the Mac-1 integrin - in bone marrow neutrophils 3h
      after LPS injection, and with increased brain levels of chemoattractants KC, MIP
      2 and MCP-1, 24 h later. In conclusion, we demonstrated that Mas receptor
      deficiency results in exacerbated inflammation in LPS-challenged mice, which
      suggest a potential role for the Mas receptor as a regulator of systemic and
      brain inflammatory response induced by LPS.

PMID- 26297427
TI  - The Akt/mTOR/p70S6K pathway is activated in IgA nephropathy and rapamycin may
      represent a viable treatment option.
AB  - IgA nephropathy (IgAN) is one of the most frequent forms of glomerulonephritis,
      and 20 to 40% of patients progress to end-stage renal disease (ESRD) within 20
      years of disease onset. However, little is known about the molecular pathways
      involved in the altered physiology of mesangial cells during IgAN progression.
      This study was designed to explore the role of mTOR signaling and the potential
      of targeted rapamycin therapy in a rat model of IgAN. After establishing an IgA
      nephropathy model, the rats were randomly divided into four groups: control,
      control+rapamycin, IgAN and IgA+rapamycin. Western blotting and
      immunohistochemistry were performed to determine phospho-Akt, p70S6K and S6
      protein levels. Coomassie Brilliant Blue was utilized to measure 24-h urinary
      protein levels. The biochemical parameters of the rats were analyzed with an
      autoanalyzer. To evaluate IgA deposition in the glomeruli, FITC-conjugated goat
      anti-rat IgA antibody was used for direct immunofluorescence. Cellular
      proliferation and the mesangial matrix in glomeruli were assayed via histological
      and morphometric procedures. Our results showed that p70S6K, S6 and Akt
      phosphorylation were significantly upregulated in IgAN rats, and rapamycin
      effectively inhibited p70S6K and S6 phosphorylation. A low dose of the mTOR
      inhibitor rapamycin reduced proteinuria, inhibited IgA deposition, and protected
      kidney function in an IgAN rat model. Low-dose rapamycin treatment corresponded
      to significantly lower cellular proliferation rates and a decreased mesangial
      matrix in the glomeruli. In conclusion, the Akt/mTOR/p70S6K pathway was activated
      in IgAN, and our findings suggested that rapamycin may represent a viable option
      for the treatment of IgAN.

PMID- 26297428
TI  - Mitochondrial OGG1 protects against PM2.5-induced oxidative DNA damage in BEAS-2B
      cells.
AB  - The enzyme 8-oxoguanine glycosylase 1 (OGG1) has been shown to be involved in the
      repair of oxidative DNA damage. However, the effect of OGG1 on oxidative DNA
      damage caused by particulate matter 2.5 (PM2.5) is unknown. Herein, we
      demonstrated that OGG1 could inhibit the generation of ROS and alleviate
      mitochondrial dysfunction and increased the expression of IL-1beta caused by
      PM2.5. The dichlorodihydrofluorescein diacetate (DCFH-DA) staining and 5,5',6,6'
      tetrachloro-1,1',3,3'-. tetraethylbenzi-midazolylcarbocyanine iodide (JC-1)
      staining using flow cytometry showed that PM2.5 induces the generation of ROS and
      leads to a reduction in mitochondrial membrane potential (MMP) in BEAS-2B cells.
      Overexpression of OGG1 inhibited the generation of ROS and the decline in MMP.
      Knockdown of OGG1 by RNA interference (RNAi) increased the generation of ROS and
      reduced the MMP. Real-time quantitative PCR (RT-qPCR) for the mitochondrial DNA
      copy number (mtDNAcn) and flow cytometry for apoptosis revealed that OGG1
      inhibits the apoptosis and decreases mtDNAcn induced by PM2.5. Additionally, the
      results of the comet assay showed that OGG1 had a significant repair effect on
      DNA strand breaks caused by PM2.5. Overexpression of OGG1 also significantly
      suppressed the expression of IL-1beta caused by PM2.5. Together, these data
      suggest that PM2.5 leads to mitochondrial dysfunction and the up-regulation of IL
      1beta could be reversed by overexpression of OGG1. The mitochondrial dysfunction
      caused by PM2.5 could be relieved by OGG1. Thus, the base excision repair enzyme
      OGG1 may alleviate mitochondrial dysfunction caused by PM2.5 involved in the
      expression of IL-1beta. 

PMID- 26297430
TI  - Monitoring of Extraction Efficiency by a Sample Process Control Virus Added
      Immediately Upon Sample Receipt.
AB  - When analysing food samples for enteric viruses, a sample process control virus
      (SPCV) must be added at the commencement of the analytical procedure, to verify
      that the analysis has been performed correctly. Samples can on occasion arrive at
      the laboratory late in the working day or week. The analyst may consequently have
      insufficient time to commence and complete the complex procedure, and the samples
      must consequently be stored. To maintain the validity of the analytical result,
      it will be necessary to consider storage as part of the process, and the
      analytical procedure as commencing on sample receipt. The aim of this study was
      to verify that an SPCV can be recovered after sample storage, and thus indicate
      the effective recovery of enteric viruses. Two types of samples (fresh and frozen
      raspberries) and two types of storage (refrigerated and frozen) were studied
      using Mengovirus vMC0 as SPCV. SPCV recovery was not significantly different (P >
      0.5) regardless of sample type or duration of storage (up to 14 days at -20 
      degrees C). Accordingly, samples can be stored without a significant effect on
      the performance of the analysis. The results of this study should assist the
      analyst by demonstrating that they can verify that viruses can be extracted from
      food samples even if samples have been stored.

PMID- 26297429
TI  - Malnutrition in Bariatric Surgery Candidates: Multiple Micronutrient Deficiencies
      Prior to Surgery.
AB  - BACKGROUND: Over 78 million American adults have obesity. Bariatric surgery is
      the leading means of durable weight loss. Nutritional deficiencies are commonly
      treated post-operatively but are often undiagnosed pre-operatively. Malnutrition
      is correlated with adverse surgical outcomes. OBJECTIVES: The aim of this study
      is to assess pre-operative nutritional status in our bariatric surgery candidates
      in a cross-sectional study. METHODS: We recruited 58 bariatric candidates
      approved to undergo the Roux-en Y gastric bypass. Nutritional status was
      determined for vitamins A, B12, D, E-alpha, and E-beta/gamma as well as thiamine,
      folate, and iron. We used clinical as well as frank deficiency cut-offs based on
      the Institute of Medicine and the World Health Organization guidelines. RESULTS:
      This cohort was largely female (77.6%) and white (63.8%). Median age was 42.2
      years. Median body mass index (BMI) was 46.3 kg/m(2). Multiple comorbidities
      (MCM) were present in 41.4%, 54.0% hypertension, 42.0% diabetic, 34.0% sleep
      apnea. Men had more comorbidities, 69.2 % with MCM. Folate and iron saturation
      varied significantly by sex. Vitamins A, D, E-alpha, and thiamine significantly
      varied by race. Vitamin D negatively correlated with BMI (p = 0.003) and age (p =
      0.030). Vitamin A negatively correlated with age (p = 0.001) and number of
      comorbidities (p = 0.003). These pre-operative bariatric candidates had
      significant malnutrition, particularly in vitamin D (92.9%) and iron (36.2 to
      56.9 %). Multiple micronutrient deficiency (MMND) was more common in blacks (50.0
      versus 39.7% overall). Number of comorbidities did not correlate with MMND.
      CONCLUSIONS: Malnutrition in one or multiple micronutrients is pervasive in this
      pre-operative bariatric cohort. The effect of pre-operative supplementation,
      especially vitamin D and iron, should be explored.

PMID- 26297431
TI  - Kaempferol Suppresses Transforming Growth Factor-beta1-Induced Epithelial-to
      Mesenchymal Transition and Migration of A549 Lung Cancer Cells by Inhibiting Akt1
      Mediated Phosphorylation of Smad3 at Threonine-179.
AB  - Kaempferol, a natural dietary flavonoid, is well known to possess chemopreventive
      and therapeutic anticancer efficacy; however, its antimetastatic effects have not
      been mechanistically studied so far in any cancer model. This study was aimed to
      investigate the inhibitory effect and accompanying mechanisms of kaempferol on
      epithelial-to-mesenchymal transition (EMT) and cell migration induced by
      transforming growth factor-beta1 (TGF-beta1). In human A549 non-small lung cancer
      cells, kaempferol strongly blocked the enhancement of cell migration by TGF-beta1
      induced EMT through recovering the loss of E-cadherin and suppressing the
      induction of mesenchymal markers as well as the upregulation of TGF-beta1
      mediated matrix metalloproteinase-2 activity. Interestingly, kaempferol reversed
      TGF-beta1-mediated Snail induction and E-cadherin repression by weakening Smad3
      binding to the Snail promoter without affecting its C-terminus phosphorylation,
      complex formation with Smad4, and nuclear translocation under TGF-beta1
      stimulation. Mechanism study revealed that the phosphorylation of Smad3 linker
      region induced by TGF-beta1 was required for the induction of EMT and cell
      migration, and selective downregulation of the phosphorylation of Smad3 at Thr179
      residue (not Ser204, Ser208, and Ser213) in the linker region was responsible for
      the inhibition by kaempferol of TGF-beta1-induced EMT and cell migration.
      Furthermore, Akt1 was required for TGF-beta1-mediated induction of EMT and cell
      migration and directly phosphorylated Smad3 at Thr179, and kaempferol completely
      abolished TGF-beta1-induced Akt1 phosphorylation. In summary, kaempferol blocks
      TGF-beta1-induced EMT and migration of lung cancer cells by inhibiting Akt1
      mediated phosphorylation of Smad3 at Thr179 residue, providing the first evidence
      of a molecular mechanism for the anticancer effect of kaempferol. 

PMID- 26297432
TI  - Gli1-Mediated Regulation of Sox2 Facilitates Self-Renewal of Stem-Like Cells and
      Confers Resistance to EGFR Inhibitors in Non-Small Cell Lung Cancer.
AB  - Non-small cell lung cancer (NSCLC) patients have very low survival rates because
      the current therapeutic strategies are not fully effective. Although EGFR
      tyrosine kinase inhibitors are effective for NSCLC patients harboring EGFR
      mutations, patients invariably develop resistance to these agents. Alterations in
      multiple signaling cascades have been associated with the development of
      resistance to EGFR inhibitors. Sonic Hedgehog and associated Gli transcription
      factors play a major role in embryonic development and have recently been found
      to be reactivated in NSCLC, and elevated Gli1 levels correlate with poor
      prognosis. The Hedgehog pathway has been implicated in the functions of cancer
      stem cells, although the underlying molecular mechanisms are not clear. In this
      context, we demonstrate that Gli1 is a strong regulator of embryonic stem cell
      transcription factor Sox2. Depletion of Gli1 or inhibition of the Hedgehog
      signaling significantly abrogated the self-renewal of stem-like side-population
      cells from NSCLCs as well as vascular mimicry of such cells. Gli1 was found to
      transcriptionally regulate Sox2 through its promoter region, and Gli1 could be
      detected on the Sox2 promoter. Inhibition of Hedgehog signaling appeared to work
      cooperatively with EGFR inhibitors in markedly reducing the viability of NSCLC
      cells as well as the self-renewal of stem-like cells. Thus, our study
      demonstrates a cooperative functioning of the EGFR signaling and Hedgehog
      pathways in governing the stem-like functions of NSCLC cancer stem cells and
      presents a novel therapeutic strategy to combat NSCLC harboring EGFR mutations. 

PMID- 26297433
TI  - Mesenchymal Stem Cells Shed Amphiregulin at the Surface of Lung Carcinoma Cells
      in a Juxtacrine Manner.
AB  - Solid tumors comprise cancer cells and different supportive stromal cells,
      including mesenchymal stem cells (MSCs), which have recently been shown to
      enhance tumor growth and metastasis. We provide new mechanistic insights into how
      bone marrow (BM)-derived MSCs co-injected with Lewis lung carcinoma cells promote
      tumor growth and metastasis in mice. The proinvasive effect of BM-MSCs exerted on
      tumor cells relies on an unprecedented juxtacrine action of BM-MSC, leading to
      the trans-shedding of amphiregulin (AREG) from the tumor cell membrane by tumor
      necrosis factor-alpha-converting enzyme carried by the BM-MSC plasma membrane.
      The released soluble AREG activates cancer cells and promotes their invasiveness.
      This novel concept is supported by the exploitation of different 2D and 3D
      culture systems and by pharmacological approaches using a tumor necrosis factor
      alpha-converting enzyme inhibitor and AREG-blocking antibodies. Altogether, we
      here assign a new function to BM-MSC in tumor progression and establish an
      uncovered link between AREG and BM-MSC. 

PMID- 26297434
TI  - Sorafenib Sensitizes Glioma Cells to the BH3 Mimetic ABT-737 by Targeting MCL1 in
      a STAT3-Dependent Manner.
AB  - The oncogenic transcription factor signal transducer and activator of
      transcription 3 (STAT3) is overactivated in malignant glioma and plays a key role
      in promoting cell survival, thereby increasing the acquired apoptosis resistance
      of these tumors. Here we investigated the STAT3/myeloid cell leukemia 1 (MCL1)
      signaling pathway as a target to overcome the resistance of glioma cells to the
      Bcl-2-inhibiting synthetic BH3 mimetic ABT-737. Stable lentiviral knockdown of
      MCL1 sensitized LN229 and U87 glioma cells to apoptotic cell death induced by
      single-agent treatment with ABT-737 which was associated with an early activation
      of DEVDase activity, cytochrome c release, and nuclear apoptosis. Similar
      sensitizing effects were observed when ABT-737 treatment was combined with the
      multikinase inhibitor sorafenib which effectively suppressed levels of
      phosphorylated STAT3 and MCL1 in MCL1-proficient LN229 and U87 glioma cells. In
      analogous fashion, these synergistic effects were observed when we combined ABT
      737 with the STAT3 inhibitor WP-1066. Lentiviral knockdown of the activating
      transcription factor 5 combined with subsequent quantitative polymerase chain
      reaction analysis revealed that sorafenib-dependent suppression of MCL1 occurred
      at the transcriptional level but did not depend on activating transcription
      factor 5 which previously had been proposed to be essential for MCL1-dependent
      glioma cell survival. In contrast, the constitutively active STAT3 mutant STAT3-C
      was able to significantly enhance MCL1 levels under sorafenib treatment to retain
      cell survival. Collectively, these data demonstrate that sorafenib targets MCL1
      in a STAT3-dependent manner, thereby sensitizing glioma cells to treatment with
      ABT-737. They also suggest that targeting STAT3 in combination with inducers of
      the intrinsic pathway of apoptosis may be a promising novel strategy for the
      treatment of malignant glioma. 

PMID- 26297435
TI  - Dynamic Change in p63 Protein Expression during Implantation of Urothelial Cancer
      Clusters.
AB  - Although the dissemination of urothelial cancer cells is supposed to be a major
      cause of the multicentricity of urothelial tumors, the mechanism of implantation
      has not been well investigated. Here, we found that cancer cell clusters from the
      urine of patients with urothelial cancer retain the ability to survive, grow, and
      adhere. By using cell lines and primary cells collected from multiple patients,
      we demonstrate that ?Np63alpha protein in cancer cell clusters was rapidly
      decreased through proteasomal degradation when clusters were attached to the
      matrix, leading to downregulation of E-cadherin and upregulation of N-cadherin.
      Decreased ?Np63alpha protein level in urothelial cancer cell clusters was
      involved in the clearance of the urothelium. Our data provide the first evidence
      that clusters of urothelial cancer cells exhibit dynamic changes in ?Np63alpha
      expression during attachment to the matrix, and decreased ?Np63alpha protein
      plays a critical role in the interaction between cancer cell clusters and the
      urothelium. Thus, because ?Np63alpha might be involved in the process of
      intraluminal dissemination of urothelial cancer cells, blocking the degradation
      of ?Np63alpha could be a target of therapy to prevent the dissemination of
      urothelial cancer. 

PMID- 26297436
TI  - Predominant Activation of JAK/STAT3 Pathway by Interleukin-6 Is Implicated in
      Hepatocarcinogenesis.
AB  - Chronic inflammation is an important process leading to tumorigenesis. Therefore,
      targeting and controlling inflammation can be a promising cancer therapy.
      Inflammation is often caused by a variety of inflammatory cytokine such as the
      interleukin (IL)-6, a pleiotrophic cytokine known to be involved in the
      tumorigenesis. In this study, an in vivo hepatic tumorigenesis model of zebrafish
      was generated to demonstrate a direct consequence of the human IL6 expression
      causing hepatocarcinogenesis. To do this, an elevated expression of the hIL6 gene
      was established to specifically target the zebrafish hepatocytes by transgenesis.
      Interestingly, the elevated hIL6 expression caused the chronic inflammation which
      results in a massive infiltration of inflammatory cells. This eventually resulted
      in the generation of various dysplastic lesions such as clear cell, small cell,
      and large cell changes, and also eosinophilic and basophilic foci of
      hepatocellular alteration. Hepatocellular carcinoma was then developed in the
      transgenic zebrafish. Molecular characterization revealed upregulation of the
      downstream components involved in the IL6-mediated signaling pathways, especially
      PI3K/Akt and JAK/STAT3 pathways. Further investigation indicated that PI3K was
      the most reactive to the infiltrated inflammatory cells and dysplasia with large
      cell change, whereas STAT3 was heavily activated in the region with dysplastic
      foci, suggesting that the JAK/STAT3 pathway was mainly implicated in the hepatic
      tumorigenesis in the current model. Our present study provides an in vivo
      evidence of the relationship between chronic inflammation and tumorigenesis and
      reinforces the pivotal role of IL6 in the inflammation-associated
      hepatocarcinogenesis. 

PMID- 26297438
TI  - Enhancement of Surfactin yield by improving the medium composition and
      fermentation process.
AB  - Surfactin is one of the most promising biosurfactants due to its extraordinary
      surface activity. Commonly, the well-established Cooper medium, a glucose-based
      mineral salt medium, is utilized for the microbial production of Surfactin. The
      current study investigated the enhancement of Surfactin yields by analyzing the
      effects of different glucose concentrations, next to the introduction of an
      alternative chelating agent and nitrogen source. The utilization of 8 g/L
      glucose, 0.008 mM Na3citrate and 50 mM (NH4)2SO4 increased Surfactin yields from
      0.7 to 1.1 g/L during shake flask experiments applying Bacillus subtilis
      DSM10(T). Consequentially conducted shake flask experiments, employing five other
      Surfactin producer strains during cultivation in the former and enhanced version
      of the Cooper medium, suggest a general enhancement of Surfactin yields during
      application of the enhanced version of the Cooper medium. The enhancement of the
      medium composition is therefore most likely independent from the employed
      producer strain. The following utilization of the enhanced medium composition
      during fed-batch fermentation with integrated foam fractionation yielded 30 %
      more Surfactin in comparison to batch fermentations with integrated foam
      fractionation employing the former version of the Cooper medium. 

PMID- 26297437
TI  - Wnt/beta-Catenin Signaling Activation beyond Robust Nuclear beta-Catenin
      Accumulation in Nondysplastic Barrett's Esophagus: Regulation via Dickkopf-1.
AB  - INTRODUCTION: Wnt/beta-catenin signaling activation has been reported only during
      the late steps of Barrett's esophagus (BE) neoplastic progression, but not in BE
      metaplasia, based on the absence of nuclear beta-catenin. However, beta-catenin
      transcriptional activity has been recorded in absence of robust nuclear
      accumulation. Thus, we aimed to investigate the Wnt/beta-catenin signaling in
      nondysplastic BE. METHODS: Esophageal tissues from healthy and BE patients
      without dysplasia were analyzed for Wnt target gene expression by quantitative
      reverse transcription polymerase chain reaction (qRT-PCR) and
      immunohistochemistry. Esophageal squamous (EPC1-& EPC2-hTERT), BE metaplastic (CP
      A), and adenocarcinoma (OE33) cell lines were characterized for Wnt activation by
      qRT-PCR, Western blot, and luciferase assay. Wnt activity regulation was examined
      by using recombinant Wnt3a and Dickkopf-1 (Dkk1) as well as Dkk1 short
      interfering RNA. RESULTS: Wnt target genes (AXIN2, c-MYC, Cyclin D1, Dkk1) and
      Wnt3a were significantly upregulated in nondysplastic BE compared with squamous
      mucosa. Elevated levels of dephosphorylated beta-catenin were detected in
      nondysplastic BE. Nuclear active beta-catenin and TOPflash activity were
      increased in CP-A and OE33 cells compared with squamous cells. Wnt3a-mediated
      beta-catenin signaling activation was abolished by Dkk1 in CP-A cells. TOPFlash
      activity was elevated following Dkk1 silencing in CP-A but not in OE33 cells.
      Dysplastic and esophageal adenocarcinoma tissues demonstrated further Dkk1 and
      AXIN2 overexpression. CONCLUSIONS: Despite the absence of robust nuclear
      accumulation, beta-catenin is transcriptionally active in nondysplastic BE. Dkk1
      overexpression regulates beta-catenin signaling in BE metaplastic but not in
      adenocarcinoma cells, suggesting that early perturbation of Dkk1-mediated
      signaling suppression may contribute to BE malignant transformation.

PMID- 26297439
TI  - Incident diabetes, hypertension and dyslipidemia in a Manitoba First Nation.
AB  - BACKGROUND: Diabetes and diabetes complications are substantially higher among
      Canadian First Nations populations compared with the general Canadian population.
      However, incidence data using detailed individual assessments from a population
      based cohort have not been undertaken. OBJECTIVE: We sought to describe incident
      diabetes, hypertension and dyslipidemia in a population-based cohort from a
      Manitoba Ojibway First Nation community. DESIGN: Study data were from 2 diabetes
      screening studies in Sandy Bay First Nation in Manitoba, Canada, collected in
      2002/2003 and 2011/2012. The cohort comprised of respondents to both screening
      studies (n=171). Health and demographic data were collected using a
      questionnaire. Fasting blood samples, blood pressure and anthropometric data were
      also collected objectively. Incident diabetes, hypertension and dyslipidemia were
      determined. Generalized linear models with Poisson distribution were used to
      estimate risk of incident diabetes and cardiometabolic conditions according to
      age and sex. RESULTS: There were 35 (95% CI: 26, 45) new cases of diabetes among
      128 participants without diabetes at baseline (27 or 3.3% per year). While
      participants who were 50 years and older at baseline had a significantly higher
      risk of incident diabetes at follow-up compared with participants aged 18-29 at
      baseline (p=0.012), more than half of the incident cases of diabetes occurred
      among participants aged less than 40 at baseline. There were 28 (95% CI: 20, 37)
      new cases of dyslipidemia at follow-up among 112 without dyslipidemia at baseline
      (25%). There were 36 (95% CI: 31, 42) new cases of hypertension among 104
      participants without hypertension at baseline (34.6%). Women had half the risk of
      developing hypertension compared with men (p=0.039). CONCLUSIONS: Diabetes
      incidence is very high, and the number of new cases among those younger than 40
      is a concern. Additional public health and primary care efforts are needed to
      address the diabetes burden in this First Nation community.

PMID- 26297440
TI  - Animal model for medication-related osteonecrosis of the jaw with precedent
      metabolic bone disease.
AB  - Despite the fact that the medications used to treat abnormal bone conditions
      often induce osteonecrosis of the jaw (ONJ), previous attempts to establish an
      animal model for ONJ have shown insufficient consideration for this important
      prerequisite for the development of the disease. The purpose of this study was to
      establish an animal model with the most common metabolic bone disease,
      osteoporosis. Ninty-six rats were randomly divided into ovariectomy (Ov) group
      (n=48) and sham-operated group (n=48). Six weeks after Ov or sham surgery, rats
      in each group were subdivided into bisphosphonate group (n=36 each) and control
      group (n=12 each) and injected with zoledronic acid and normal saline,
      respectively, once a week. After additional 6weeks, surgical intervention was
      performed, and the injections were continued for 8 more weeks. The animals were
      then sacrificed for further macroscopic, histological, histomorphometric,
      radiological, and bone biomarker investigations. As histologically determined,
      the Ov group (77.8%) showed higher ONJ prevalence compared to the sham group
      (47.2%; P<0.05). Micro-structural and histomorphometric assessments revealed that
      rats with ONJ (ONJ group) presented with deteriorated bone architectures with
      higher necrotic bone fraction and lower number of osteoclasts (P<0.05). Compared
      to the sham-operated ONJ group, the Ov ONJ group showed significantly lower
      values of Tb.N, Tb.Sp, Conn.D, N.Oc/T.Ar, and TRACP 5b and CTX/TRACP (P<0.05).
      The ovariectomized rat model in this study successfully mimicked human ONJ
      lesions with an underlying bone disease and showed different bone characteristics
      than that of the previous ONJ model. Based on the differences, further researches
      for investigating pathophysiology of ONJ, including various pharmacological
      responses for deteriorated bone environment, are required. 

PMID- 26297441
TI  - Fine mapping of bone structure and strength QTLs in heterogeneous stock rat.
AB  - We previously demonstrated that skeletal structure and strength phenotypes vary
      considerably in heterogeneous stock (HS) rats. These phenotypes were found to be
      strongly heritable, suggesting that the HS rat model represents a unique genetic
      resource for dissecting the complex genetic etiology underlying bone fragility.
      The purpose of this study was to identify and localize genes associated with bone
      structure and strength phenotypes using 1524 adult male and female HS rats
      between 17 to 20 weeks of age. Structure measures included femur length, neck
      width, head width; femur and lumbar spine (L3-5) areas obtained by DXA; and cross
      sectional areas (CSA) at the midshaft, distal femur and femoral neck, and the 5th
      lumbar vertebra measured by CT. In addition, measures of strength of the whole
      femur and femoral neck were obtained. Approximately 70,000 polymorphic SNPs
      distributed throughout the rat genome were selected for genotyping, with a mean
      linkage disequilibrium coefficient between neighboring SNPs of 0.95. Haplotypes
      were estimated across the entire genome for each rat using a multipoint haplotype
      reconstruction method, which calculates the probability of descent at each locus
      from each of the 8 HS founder strains. The haplotypes were then tested for
      association with each structure and strength phenotype via a mixed model with
      covariate adjustment. We identified quantitative trait loci (QTLs) for structure
      phenotypes on chromosomes 3, 8, 10, 12, 17 and 20, and QTLs for strength
      phenotypes on chromosomes 5, 10 and 11 that met a conservative genome-wide
      empiric significance threshold (FDR=5%; P<3*10(-6)). Importantly, most QTLs were
      localized to very narrow genomic regions (as small as 0.3 Mb and up to 3 Mb),
      each harboring a small set of candidate genes, both novel and previously shown to
      have roles in skeletal development and homeostasis.

PMID- 26297443
TI  - Anti-inflammatory and antinociceptive effects of racemic goniothalamin, a styryl
      lactone.
AB  - AIMS: The present study aimed to further investigate the anti-inflammatory
      activity of goniothalamin (GTN), a styryl lactone, as well as its antinociceptive
      effects. MAIN METHODS: The anti-inflammatory activity was evaluated in models of
      paw edema induced by different mediators in mice and carrageenan-induced
      peritonitis. Evaluation of the antinociceptive effect was performed through
      acetic acid-induced writhing test and formalin test. Activity of GTN on gene
      expression levels of interleukin-1beta (IL-1beta), induced nitric oxidase
      synthase (iNOS) and cyclooxygenase-2 (COX-2) were evaluated in vitro in
      lipopolysaccharide (LPS)-stimulated macrophage (RAW 264.7), as well as gene
      expression and protein levels of tumor necrosis factor-alpha (TNF-alpha). KEY
      FINDINGS: Pretreatment with GTN (300 mg/kg) significantly reduced paw edema
      induced by compound 48/80, prostaglandin E2, phospholipase A2 and bradykinin. GTN
      (10, 30 and 100mg/kg) inhibited leukocyte migration in the peritonitis model and
      gene expression levels of IL-1beta, iNOS and TNF-alpha, as well as TNF-alpha
      protein levels, in LPS-stimulated macrophages, without affecting COX-2 gene
      expression levels. GTN inhibited nociception induced by acetic acid in the
      writhing model and in the formalin test, when both neurogenic and inflammatory
      phases were inhibited. SIGNIFICANCE: For the first time the acute anti
      inflammatory profile of GTN is characterized and its antinociceptive activity
      reported. The current study shows that GTN inhibits both vascular and cellular
      phases of inflammation, with bradykinin and PLA2 induced inflammation being the
      most affected by GTN. Its anti-inflammatory effects also involved the in vitro
      inhibition of gene expression of alarm cytokines and mediators as IL-1beta, iNOS
      and TNF-alpha.

PMID- 26297442
TI  - Plasma periostin associates significantly with non-vertebral but not vertebral
      fractures in postmenopausal women: Clinical evidence for the different effects of
      periostin depending on the skeletal site.
AB  - BACKGROUND: Periostin is preferentially expressed by the periosteum, which mainly
      covers the long bones. Therefore, the role of periostin in osteoporotic fracture
      (OF) may differ depending on bone type. We performed a case-control study to
      investigate whether periostin can serve as a predictor of OF risk, particularly
      after dividing OFs into non-vertebral and vertebral fractures. METHODS: Among 532
      consecutive postmenopausal women not taking any drug or without any disease that
      could affect bone metabolism, 133 cases with OF (i.e., non-vertebral and/or
      vertebral fractures) and 133 age- and body mass index-matched controls were
      enrolled. Non-vertebral (i.e., forearm, humerus, hip, and pelvis; n=81) and
      morphological vertebral (n=62) fractures were identified by an interviewer
      assisted questionnaire and lateral thoracolumbar radiographs, respectively. Bone
      mineral density (BMD) and plasma periostin levels were also measured. RESULTS:
      Plasma periostin was markedly higher in subjects with non-vertebral fracture than
      their controls even after adjustment for BMD and potential confounders (P=0.006).
      Each standard deviation increment of plasma periostin was associated with a
      multivariable-adjusted odds ratio of 1.59 for non-vertebral fracture. The odds
      for non-vertebral fracture were 2.48-fold higher in subjects in the highest
      periostin tertile compared with those in the lowest periostin tertile (95%
      confidence interval=1.10-5.61). However, associations between plasma periostin
      and vertebral fracture were not observed, regardless of the adjustment model
      used. Consistently, plasma periostin levels were inversely associated with
      proximal femur BMD (P=0.007 to 0.030) but not lumbar spine BMD. In subgroup
      analyses, plasma periostin had no correlation with the levels of classical bone
      turnover markers. CONCLUSIONS: Plasma periostin may be a potential biomarker of
      the risk of OF, especially in non-spinal skeletal sites, such as the limbs,
      rather than spine.

PMID- 26297445
TI  - Obesity and cancer phenotype: Is angiogenesis a missed link?
AB  - Obesity remains nowadays one of the main threats to human health, being a problem
      of worldwide proportions. It is characterized by augmented storage of fatty acids
      in an enlarged adipose tissue. This process is possible thanks to a rich
      capillary network, supported by a mechanism that has also a crucial role on
      cancer: angiogenesis. Given that several studies point obesity as a risk factor
      for cancer development, angiogenesis may be approached as the missed link between
      these two pathologies. Understanding the different pathways behind angiogenesis
      becomes essential to break this link by developing new anti-angiogenic therapies
      or improving the actual ones. In the first phase, this paper will focus the
      structural and cellular changes that adipose tissue suffers in obesity. Then, the
      main pro-angiogenic players will be reviewed, taking into account the pathways
      that explain their putative role in obesity-cancer link. Finally, the clinical
      implications of the presented mechanisms will also be regarded, being the main
      focus on the anti-angiogenic therapies. 

PMID- 26297444
TI  - Thiopental protects human neuroblastoma cells from apoptotic cell death -
      Potential role of heat shock protein 70.

PMID- 26297446
TI  - Isolation and characterization of a novel Helicobacter species, Helicobacter
      jaachi sp. nov., from common marmosets (Callithrix jaachus).
AB  - Purpose-bred common marmosets from domestic sources housed in a US research
      facility, and used in multiple drug discovery programmes, were noted to have a
      high incidence of spontaneous inflammatory bowel disease and sporadic
      cholecystitis and cholangiohepatitis. Inflammatory infiltrates increased in
      incidence and severity with age. Because Helicobacter spp. have been linked to
      gastrointestinal diseases, samples from the gastrointestinal tracts of 39
      marmosets were screened for Helicobacter spp. by culture and PCR. Helicobacter
      spp. were frequently detected in marmosets; 28.2% of the marmosets were positive
      for a proposed novel species, Helicobacter jaachi sp. nov., by culture, and 48.7%
      were positive by Helicobacter genus-specific PCR. Seventeen strains of
      Helicobacter sp. from 11 marmosets were cultured from various gastrointestinal
      sites. Older animals (age 6-11 years) had a higher helicobacter prevalence rate
      (57.1%) compared with younger animals (age 3-5 years), which had a 27.2%
      prevalence rate. Cells of H. jaachi sp. nov. were catalase, urease and oxidase
      positive and had fusiform morphology, with periplasmic fibres and multiple
      bipolar, sheathed flagella. All isolates had similar 16S and 23S rRNA sequences,
      which clustered as representatives of a novel Helicobacter species closely
      related to 'Helicobacter sanguini' (97%), a species isolated from cotton-top
      tamarins and 'Helicobacter callitrichis' (96%) isolated previously from the
      faeces of common marmosets. The whole genome sequence of one of the liver
      isolates, H. jaachi sp. nov. MIT 09-6949(T), had a 1.9 Mb genome length with a 41
      mol% DNA G+C content. The type strain of Helicobacter jaachi sp. nov., MIT 09
      6949(T), has been deposited in the BCCM/LMG Bacteria Collection as LMG 28613(T).
      These findings add to the increasing number of animal species with
      gastrointestinal disease in which novel enterohepatic Helicobacter spp. have been
      isolated.

PMID- 26297447
TI  - Implementation of the HealthKick intervention in primary schools in low-income
      settings in the Western Cape Province, South Africa: a process evaluation.
AB  - BACKGROUND: The HealthKick intervention, introduced at eight primary schools in
      low-income settings in the Western Cape Province, South Africa, aimed to promote
      healthy lifestyles among learners, their families and school staff. Eight schools
      from similar settings without any active intervention served as controls.
      METHODS: The Action Planning Process (APP) guided school staff through a process
      that enabled them to assess areas for action; identify specific priorities; and
      set their own goals regarding nutrition and physical activity at their schools.
      Educators were introduced to the APP and trained to undertake this at their
      schools by holding workshops. Four action areas were covered, which included the
      school nutrition environment; physical activity and sport environment; staff
      health; and chronic disease and diabetes awareness. Intervention schools also
      received a toolkit comprising an educator's manual containing planning guides,
      printed resource materials and a container with physical activity equipment. To
      facilitate the APP, a champion was identified at each school to drive the APP and
      liaise with the project team. Over the three-years a record was kept of
      activities planned and those accomplished. At the end of the intervention, focus
      group discussions were held with school staff at each school to capture
      perceptions about the APP and intervention activities. RESULTS: Overall uptake of
      events offered by the research team was 65.6% in 2009, 75% in 2010 and 62.5% in
      2011. Over the three-year intervention, the school food and nutrition environment
      action area scored the highest, with 55.5% of planned actions being undertaken.
      In the chronic disease and diabetes awareness area 54.2% actions were completed,
      while in the school physical activity and sport environment and staff health
      activity areas 25.9 and 20% were completed respectively. According to educators,
      the low level of implementation of APP activities was because of a lack of
      parental involvement, time and available resources, poor physical environment at
      schools and socio-economic considerations. CONCLUSIONS: The implementation of the
      HealthKick intervention was not as successful as anticipated. Actions required
      for future interventions include increased parental involvement, greater support
      from the Department of Basic Education and assurance of sufficient motivation and
      'buy-in' from schools.

PMID- 26297448
TI  - Childhood Immunizations: First-Time Expectant Mothers' Knowledge, Beliefs,
      Intentions, and Behaviors.
AB  - INTRODUCTION: This study focused on how first-time mothers decide or intend to
      decide with respect to the recommended childhood immunization schedule. METHODS:
      This was the baseline survey of a larger longitudinal survey. Data were collected
      between June and September 2014 from 200 first-time mothers in their second
      trimester of pregnancy to examine vaccine-related knowledge, perceptions,
      intentions, and information-seeking behavior. RESULTS: Data were analyzed between
      January and June 2015. Seventy-five percent planned to have their child receive
      all the vaccinations consistent with the recommended childhood immunization
      schedule. Although participants expressed interest in childhood vaccine
      information, most had not received information directly from a primary care
      provider. One third reported receiving such information from their
      obstetrician/gynecologist but only about half of those were "very satisfied" with
      the information they received. About 70% indicated they were not familiar with
      the recommended vaccination schedule and number of routinely recommended
      vaccines. Familiarity with common vaccine education messages varied widely. Women
      who indicated they were planning to delay one or more recommended vaccinations
      were most likely to rely on Internet searches for childhood vaccine information.
      CONCLUSIONS: Overall, respondents had relatively positive beliefs and perceptions
      regarding childhood vaccines, which were associated with intentions to get their
      newborn vaccinated as recommended. However, most who were planning to delay
      recommended vaccinations or were undecided relied primarily on socially available
      sources of vaccine information, rather than information provided by a healthcare
      professional. Improved access to vaccine information from healthcare
      professionals could foster better vaccine-related knowledge and favorably impact
      vaccination decisions.

PMID- 26297449
TI  - Predictors of Vaccination in India for Children Aged 12-36 Months.
AB  - INTRODUCTION: India has one of the lowest immunization rates worldwide despite a
      longstanding Universal Immunization Program (UIP) that provides free childhood
      vaccines. This study characterizes the predictors for under- and non-vaccination
      among Indian children aged 12-36 months. METHODS: This study utilized District
      Level Household and Facility Survey Data, 2008 (DLHS3), from India. DLHS3 is a
      nationally representative sample collected from December 2007 through December
      2008; this analysis was conducted during 2014. Children's vaccination status was
      categorized as fully, under-, and non-vaccinated based on whether children
      received all, some, or none of the UIP-recommended vaccines (one dose each of
      bacillus Calmette-Guerin and measles, and three doses of diphtheria-pertussis
      tetanus). A multinomial logistic regression model estimated the odds of under
      vaccination compared with full vaccination, and odds of non-vaccination compared
      with full vaccination. Analytic predictors included socioeconomic, cultural,
      household, maternal, and childhood characteristics. RESULTS: The analysis
      included 108,057 children; the estimated proportions of fully, under-, and non
      vaccinated children were 57%, 31%, and 12%, respectively. After adjusting for
      state of residence, age, gender, household wealth, and maternal education,
      additional significant predictors of children's vaccination status were religion,
      caste, place of delivery, number of antenatal care visits, and maternal tetanus
      vaccination, all of which demonstrated large effect sizes. CONCLUSIONS: India's
      immunization coverage remained low in 2008, with just slightly more than half of
      all children aged 12-36 months fully vaccinated with UIP-recommended vaccines. A
      better understanding of the predictors for vaccination can help shape
      interventions to reduce disparities in full vaccination among children of
      differing demographic/cultural groups.

PMID- 26297450
TI  - Lessons Learned From Making and Implementing Vaccine Recommendations in the U.S.
AB  - After publication of certain vaccine recommendations made by the Advisory
      Committee on Immunization Practices, several unexpected events have occurred
      during implementation of these recommendations. These have included changes in
      recommendations following adverse events involved with a particular vaccine and
      the conferral of community protection as an offshoot of vaccination of a specific
      population. Vaccine shortages and hesitancy have also been proven impediments to
      full implementation, and vaccine recommendations have not gone unaffected by
      either public perception of a vaccine or by cost considerations. 

PMID- 26297451
TI  - Racial and Ethnic Disparities in Vaccination Coverage Among Adult Populations in
      the U.S.
AB  - INTRODUCTION: Reducing racial/ethnic disparities in immunization rates is a
      compelling public health goal. Disparities in childhood vaccination rates have
      not been observed in recent years for most vaccines. The objective of this study
      is to assess adult vaccination by race/ethnicity in the U.S. METHODS: The 2012
      National Health Interview Survey was analyzed in 2014 to assess adult vaccination
      by race/ethnicity for five vaccines routinely recommended for adults: influenza,
      tetanus, pneumococcal (two vaccines), human papilloma virus, and zoster vaccines.
      Multivariable logistic regression analysis was performed to identify factors
      independently associated with all adult vaccinations. RESULTS: Vaccination
      coverage was significantly lower among non-Hispanic blacks, Hispanics, and non
      Hispanic Asians compared with non-Hispanic whites, with only a few exceptions.
      Age, sex, education, health insurance, usual place of care, number of physician
      visits in the past 12 months, and health insurance were independently associated
      with receipt of most of the examined vaccines. Racial/ethnic differences
      narrowed, but gaps remained after taking these factors into account. CONCLUSIONS:
      Racial and ethnic differences in vaccination levels narrow when adjusting for
      socioeconomic factors analyzed in this survey, but are not eliminated, suggesting
      that other factors that are associated with vaccination disparities are not
      measured by the National Health Interview Survey and could also contribute to the
      differences in coverage. Additional efforts, including systems changes to ensure
      routine assessment and recommendations for needed vaccinations among adults for
      all racial/ethnic groups, are essential for improving vaccine coverage.

PMID- 26297453
TI  - Urchin-like gold nanoparticle-based immunochromatographic strip test for rapid
      detection of fumonisin B1 in grains.
AB  - An immunochromatographic strip (ICS) using urchin-like gold nanoparticles (UGNs)
      for sensitive detection of fumonisin B1 (FB1) was developed to meet the
      requirement for rapidly monitoring FB1 in grain samples. The sensitivity of the
      ICS was 5.0 ng/mL, which represents a fourfold increase in sensitivity over
      conventional strip preparation using colloidal gold as the antibody-labeled
      probe. Analysis of FB1 in grain samples showed that data obtained from the strip
      tests were in a good agreement with those obtained from HPLC and enzyme-linked
      immunosorbent assays (ELISAs). This qualitative test did not require any
      specialized equipment, and the detection time was less than 5 min, which is
      suitable for on-site testing of FB1 in grain samples. Overall, to our knowledge,
      this is the first report of using a UGN as the antibody-labeled probe for
      sensitive detection of FB1 in grains using an ICS. Graphical Abstract Preparation
      of ICS using conventional colloidal gold and urchin-like gold nanoparticle,
      respectively. 

PMID- 26297452
TI  - The roles of tetrapyrroles in plastid retrograde signaling and tolerance to
      environmental stresses.
AB  - MAIN CONCLUSION: This review provides new insights that tetrapyrrole signals play
      important roles in nuclear gene expression, chloroplast development and plant's
      resistance to environmental stresses. Higher plants contain many tetrapyrroles,
      including chlorophyll (Chl), heme, siroheme, phytochromobilin and some of their
      precursors, all of which have important biological functions. Genetic and
      physiological studies indicated that tetrapyrrole (mainly Mg-protoporphyrin IX)
      retrograde signals control photosynthesis-associated nuclear gene (PhANG)
      expression. Recent studies have shown that tetrapyrrole-derived signals may
      correlate with plant resistance to environmental stresses such as drought, high
      light stress, water stress, osmotic stress, salinity and heavy metals. Signaling
      and physiological roles of Mg-protoIX-binding proteins (such as PAPP5, CRD and
      HSP90) and heme-binding proteins (such as HO and TSPO) and tetrapyrrole-signaling
      components (such as GUN1, ABI4 and CBFA) are summarized. Some of them positively
      regulate plant development and response to environmental stresses. The
      intermediate signaling components (such as PTM, HSP70-HSP90-HAP1 complex and
      PAPP5) between the nucleus and the plastid also positively regulate plant
      resistance to environmental stresses. This review provides new insights that
      genetically modified plants with enhanced tetrapyrrole levels have improved
      resistance to environmental stresses.

PMID- 26297454
TI  - Fast analysis of glibenclamide and its impurities: quality by design framework in
      capillary electrophoresis method development.
AB  - A fast capillary zone electrophoresis method for the simultaneous analysis of
      glibenclamide and its impurities (I(A) and I(B)) in pharmaceutical dosage forms
      was fully developed within a quality by design framework. Critical quality
      attributes were represented by I(A) peak efficiency, critical resolution between
      glibenclamide and I(B), and analysis time. Experimental design was efficiently
      used for rapid and systematic method optimization. A 3(5)//16 symmetric screening
      matrix was chosen for investigation of the five selected critical process
      parameters throughout the knowledge space, and the results obtained were the
      basis for the planning of the subsequent response surface study. A Box-Behnken
      design for three factors allowed the contour plots to be drawn and the design
      space to be identified by introduction of the concept of probability. The design
      space corresponded to the multidimensional region where all the critical quality
      attributes reached the desired values with a degree of probability pi >= 90%.
      Under the selected working conditions, the full separation of the analytes was
      obtained in less than 2 min. A full factorial design simultaneously allowed the
      design space to be validated and method robustness to be tested. A control
      strategy was finally implemented by means of a system suitability test. The
      method was fully validated and was applied to real samples of glibenclamide
      tablets.

PMID- 26297455
TI  - Quantitative determination of 2-amino-2-(2-(4'-(2-propyloxazol-4-yl)-[1,1'
      biphenyl]-4-yl)ethyl)propane-1,3-diol and its active phosphorylated metabolite in
      rat blood by LC-MS/MS and application to PK/PD analysis.
AB  - A sensitive and specific LC-MS/MS method was developed and validated for
      simultaneous determination of 2-amino-2-(2-(4'-(2-propyloxazol-4-yl)-[1,1'
      biphenyl]-4-yl)ethyl)propane-1,3-diol (SYL930) and its active phosphate
      metabolite (SYL930-P) in rat blood using SYL927, an analogue of SYL930 as the
      internal standard. Blood samples were prepared by a simple protein precipitation
      with acetonitrile. The chromatographic separation was performed on a ZorbaxSB-C18
      column (3.5 MUm, 2.1 * 100 mm) with a gradient mobile phase of methanol/water
      containing 0.1 % formic acid (v/v) at a flow rate of 0.2 mL/min. The detection
      was carried out on a triple quadrupole tandem mass spectrometer equipped with
      electrospray ionization (ESI) in multiple reactions monitoring mode (MRM). The
      monitored transitions were 381.2 -> 364.2 for SYL930, 461.2 -> 334.2 for SYL930
      P, and 367.1 -> 350.4 for the internal standard, respectively. Good linearity was
      obtained for the analytes over the range of 0.2-100 ng/mL for SYL930 and 0.5-100
      ng/mL for SYL930-P. The lower limits of quantitation (LLOQs) for SYL930 and
      SYL930-P were 0.2 and 0.5 ng/mL, respectively. The intra-day and inter-day
      precisions (RSD, %) of analytes were within 9.87 %, and the accuracy (RE, %)
      ranged from -7.04 to 13.15 %. The mean recoveries for two compounds in rat blood
      were 87.9-109 %. The analytes were proved to be stable during all sample storage,
      preparation, and analytic procedures. The validated method was successfully
      applied to pharmacokinetic and PK/PD studies of SYL930 and SYL930-P in rats after
      oral administration of SYL930. Graphical Abstract Quantitative determination of
      SYL930 and its active phosphorylated metabolite in rat blood by LCMS/MS and
      application to PK/PD analysis. 

PMID- 26297456
TI  - Selective extraction of gallic acid in pomegranate rind using surface imprinting
      polymers over magnetic carbon nanotubes.
AB  - A novel surface imprinting polymer based on magnetic carbon nanotubes was
      prepared using dendritic polyethyleneimine as functional monomer to amplify the
      number of imprinted cavities. The characteristics of resulting polymers were
      evaluated by transmission electron microscopy (TEM), X-ray diffraction (XRD),
      Fourier-transform infrared spectroscopy (FT-IR), and vibrating sample
      magnetometer (VSM). Results suggest that magnetic nanoparticles are deposited
      onto the surface of multiwalled carbon nanotubes and the imprinted shell is
      coated on the surface of magnetic carbon nanotubes with a thickness of
      approximately 8 nm. Magnetic imprinted polymers are sensitive to magnetic fields
      and can be easily separated within 3 s using an external magnet. The adsorption
      results indicate that the obtained imprinted polymers have fast kinetics, an
      ultrahigh adsorption capacity of 479.9 mg g(-1), and satisfactory selectivity
      towards the template molecule. The prepared materials have excellent stability
      with no obvious deterioration after six adsorption-regeneration cycles. In
      addition, a method for determination of gallic acid (GA) in pomegranate rind was
      developed, using a combination of the prepared polymers used as solid-phase
      extraction (SPE) sorbents and high-performance liquid chromatography (HPLC) for
      rapid isolation and determination of GA. The limit of detection of the proposed
      method is 0.001 MUg mL(-1), and the intra and inter-day relative standard
      deviations (RSDs) are lower than 3.8% and 5.3%, respectively. The recoveries of
      GA from pomegranate rind extract are in the range 98.2-103.6% with RSDs lower
      than 4.3%.

PMID- 26297457
TI  - Tailored 96-well MUElution solid-phase extraction combined with UFLC-MS/MS: a
      significantly improved approach for determination of free 3-nitrotyrosine in
      human urine.
AB  - We developed and validated a simple and fast UFLC-MS/MS method for the accurate
      determination of 3-nitrotyrosine (3-NT) in human urine as a noninvasive biomarker
      for oxidative stress. The method, involving tailored 96-well MUElution solid
      phase extraction (SPE) combined with UFLC-MS/MS, allows 3-NT to be determined in
      biological samples without the need for hydrolysis, derivatization, evaporation,
      and two-dimensional LC for the first time. Using ammonium acetate (pH 9, 25 mM)
      as an elution buffer was found to improve SPE selectivity. Fast chromatographic
      elution of 3-NT with a total run time of 7 min was achieved on a PFPP column (150
      mm * 2.1 mm, 3 MUm). This fine-tuned integrated method delivered significantly
      improved throughput, specificity, and sensitivity while reducing the matrix
      effect, solvent usage, and waste disposal. Using this simple and rapid method,
      two plates of urine samples (n = 192) can be processed within 24 h. The lower
      limit of quantification for 3-NT is 10 pg/mL, which represents a notable
      sensitivity enhancement over reported methods. Less than 6.0 % variations for
      intraday and interday assay precisions and 97.7-106.3% for accuracies in terms of
      recovery were obtained. The applicability and reliability of the method were
      demonstrated by determining the reference range in human urine for 82 healthy
      people. Considering the noninvasive and inexpensive nature of urine sampling,
      this novel method could be used to re-evaluate the role of 3-NT as an oxidative
      stress biomarker in pre-clinical and clinical studies.

PMID- 26297458
TI  - Identification of Ginkgo biloba supplements adulteration using high performance
      thin layer chromatography and ultra high performance liquid chromatography-diode
      array detector-quadrupole time of flight-mass spectrometry.
AB  - Ginkgo biloba is one of the most widely sold herbal supplements and medicines in
      the world. Its popularity stems from having a positive effect on memory and the
      circulatory system in clinical studies. As ginkgo popularity increased, non
      proprietary extracts were introduced claiming to have a similar phytochemical
      profile as the clinically tested extracts. The standardized commercial extracts
      of G. biloba leaf used in ginkgo supplements contain not less than 6%
      sesquiterpene lactones and 24% flavonol glycosides. While sesquiterpene lactones
      are unique constituents of ginkgo leaf, the flavonol glycosides are found in many
      other botanical extracts. Being a high value botanical, low quality ginkgo
      extracts may be subjected to adulteration with flavonoids to meet the requirement
      of 24% flavonol glycosides. Chemical analysis by ultra high performance liquid
      chromatography-mass spectrometry revealed that adulteration of ginkgo leaf
      extracts in many of these products is common, the naturally flavonol glycoside
      rich extract being spiked with pure flavonoids or extracts made from another
      flavonoid-rich material, such as the fruit/flower of Japanese sophora
      (Styphnolobium japonicum), which also contains the isoflavone genistein.
      Recently, genistein has been proposed as an analytical marker for the detection
      of adulteration of ginkgo extracts with S. japonicum. This study confirms that
      botanically authenticated G. biloba leaf and extracts made therefrom do not
      contain genistein, and the presence of which even in trace amounts is suggestive
      of adulteration. In addition to the mass spectrometric approach, a high
      performance thin layer chromatography method was developed as a fast and economic
      method for chemical fingerprint analysis of ginkgo samples.

PMID- 26297459
TI  - A biosensor based on electroactive dipyrromethene-Cu(II) layer deposited onto
      gold electrodes for the detection of antibodies against avian influenza virus
      type H5N1 in hen sera.
AB  - This paper describes the development of a biosensor for the detection of anti
      hemagglutinin antibodies against the influenza virus hemagglutinin. The steps of
      biosensor fabrications are as follows: (i) creation of a mixed layer containing
      the thiol derivative of dipyrromethene and 4-mercapto-1-butanol, (ii)
      complexation of Cu(II) ions, (iii) oriented immobilization of the recombinant
      histidine-tagged hemagglutinin, and (iv) filling free spaces with bovine serum
      albumin. The interactions between recombinants hemagglutinin from the highly
      pathogenic avian influenza virus type H5N1 and anti-hemagglutinin H5 monoclonal
      antibodies were explored with Osteryoung square-wave voltammetry. The biosensor
      displayed a good detection limit of 2.4 pg/mL, quantification limit of 7.2 pg/mL,
      and dynamic range from 4.0 to 100.0 pg/mL in buffer. In addition, this analytical
      device was applied for the detection of antibodies in hen sera from individuals
      vaccinated and non-vaccinated against the avian influenza virus type H5N1. The
      limit of detection for the assay was the dilution of sera 1: 7 * 10(6), which is
      about 200 times better than the enzyme-linked immunosorbent assay.

PMID- 26297460
TI  - Discrimination of urinary tract infection pathogens by means of their growth
      profiles using surface enhanced Raman scattering.
AB  - Urinary tract infection (UTI) is a widespread infection and affects millions of
      people around the globe. The gold standard for identification of microorganisms
      causing infection is urine culture. However, current methods require at least 24
      h for the results. In clinical settings, identification and discrimination of
      bacteria with less time-consuming and cheaper methods are highly desired. In
      recent years, the power of surface-enhanced Raman scattering (SERS) for fast
      identification of bacteria and biomolecules has been demonstrated. In this study,
      we show discrimination of urinary tract infection causative pathogens within 1 h
      of incubation using principal component analysis (PCA) of SERS spectra of seven
      different UTI causative bacterial species. In addition, we showed differentiation
      of them at their different growth phases. We also analyzed origins of bacterial
      SERS spectra and demonstrated the highly dynamic structure of the bacteria cell
      wall during their growth. Graphical Abstract Collection of bacteria from urine
      sample, and their discrimination using their SERS spectra and multivariate
      analysis. 

PMID- 26297461
TI  - Metabolism of the new psychoactive substances N,N-diallyltryptamine (DALT) and 5
      methoxy-DALT and their detectability in urine by GC-MS, LC-MSn, and LC-HR-MS-MS.
AB  - N,N-Diallyltryptamine (DALT) and 5-methoxy-DALT (5-MeO-DALT) are synthetic
      tryptamine derivatives commonly referred to as so-called new psychoactive
      substances (NPS). They have psychoactive effects that may be similar to those of
      other tryptamine derivatives. The objectives of this work were to study the
      metabolic fate and detectability, in urine, of DALT and 5-MeO-DALT. For
      metabolism studies, rat urine obtained after high-dose administration was
      prepared by precipitation and analyzed by liquid chromatography-high-resolution
      mass spectrometry (LC-HR-MS-MS). On the basis of the metabolites identified,
      several aromatic and aliphatic hydroxylations, N-dealkylation, N-oxidation, and
      combinations thereof are proposed as the main metabolic pathways for both
      compounds. O-Demethylation of 5-MeO-DALT was also observed, in addition to
      extensive glucuronidation or sulfation of both compounds after phase I
      transformation. The cytochrome P450 (CYP) isoenzymes predominantly involved in
      DALT metabolism were CYP2C19, CYP2D6, and CYP3A4; those mainly involved in 5-MeO
      DALT metabolism were CYP1A2, CYP2C19, CYP2D6, and CYP3A4. For detectability
      studies, rat urine was screened by GC-MS, LC-MS(n), and LC-HR-MS-MS after
      administration of low doses. LC-MS(n) and LC-HR-MS-MS were deemed suitable for
      monitoring consumption of both compounds. The most abundant targets were a ring
      hydroxy metabolite of DALT, the N,O-bis-dealkyl metabolite of 5-MeO-DALT, and
      their glucuronides. GC-MS enabled screening of DALT by use of its main
      metabolites only.

PMID- 26297463
TI  - UHPLC-high-resolution mass spectrometry determination of bisphenol A and plastic
      additives released by polycarbonate tableware: influence of ageing and surface
      damage.
AB  - A new UHPLC-ESI-Orbitrap method for the identification and the quantitative
      determination of bisphenol A and some common additives employed in plastic
      manufacturing has been developed and validated. The method has been applied to
      evaluate the migration from 14 samples of tableware of different age and degree
      of surface damage, in both ethanol and isooctane (used as food simulants
      according to EU plastic regulation). Bisphenol A, three UV light absorbers, and
      one whitening agent were detected and quantified. Data were analyzed with the aim
      of exploring a possible correlation between bisphenol A and additives release,
      ageing, and surface integrity. A high correlation between age of samples, surface
      damage, and bisphenol A migration has been evaluated, while the release of
      additives was not correlated with other parameters. Obtained data showed for the
      first time that the release of bisphenol A seems to be more connected to ageing
      than to scratches and cracks occurrence. Graphical Abstract Bisphenol A and
      additives released by polycarbonate tableware: influence of ageing and surface
      damage. 

PMID- 26297462
TI  - Chemiluminescent aptasensor for chloramphenicol based on N-(4-aminobutyl)-N
      ethylisoluminol-functionalized flower-like gold nanostructures and magnetic
      nanoparticles.
AB  - A novel chemiluminescent aptasensor for the highly sensitive detection of
      chloramphenicol (CAP) in milk was successfully developed using biotinylated CAP
      aptamer-functionalized magnetic nanoparticles (MNPs) as capture probes and
      thiolated hybridized complementary strand-modified N-(4-aminobutyl)-N
      ethylisoluminol (ABEI)-functionalized flower-like gold nanostructures (AuNFs) as
      signal probes. P-iodophenol (PIP) was also added to form an ABEI-H2O2-PIP steady
      state chemiluminescence (CL) system. Based on a competitive format, the CL
      intensity was negatively correlated with the concentration of CAP in the range of
      0.01-0.20 ng/mL and the detection limit was 0.01 ng/mL in buffer and 1 ng/mL in
      milk. The proposed method was successfully applied to measure CAP in milk samples
      and compared to a commercial ELISA method. The high sensitivity of AuNFs,
      excellent selectivity and stability of aptamers, and good overall stability of
      the chemiluminescent bioassay with magnetic separation make them a promising
      approach for the detection of small molecular illegal additives. Additionally,
      the high sensitivity, easy operation, and good reproducibility exhibited by the
      stable chemiluminescent bioassay demonstrate its applicability for the trace
      detection of CAP in applications, such as animal husbandry. 

PMID- 26297464
TI  - In vivo confocal Raman microspectroscopy of the human skin: highlighting of
      spectral markers associated to aging via a research of correlation between Raman
      and biometric mechanical measurements.
AB  - Skin plays a protective role against the loss of water and external aggression,
      including mechanical stresses. These crucial functions are ensured by different
      cutaneous layers, particularly the stratum corneum (SC). During aging, the human
      skin reveals some apparent modifications of functionalities such as a loss of
      elasticity. Our investigations aimed at demonstrating that Raman
      microspectroscopy, as a label-free technique with a high molecular specificity,
      is efficient to assess in vivo the molecular composition of the skin and the
      alterations underwent during aging. Our approach was based on a search for
      correlation between Raman data collected on healthy female volunteers of
      different ages (from 21 to 70 years old) by means of a remote confocal Raman and
      skin firmness measurements used as a reference method. Raman and biometric data
      were then submitted to a partial least square (PLS)-based data processing. Our
      experiments demonstrated the potential of Raman microspectroscopy to provide an
      objective in vivo assessment of the skin "biological age" that can be very
      different from the "chronological age" of the person. In addition, Raman features
      sensitive to the elasticity and the fatigability of the SC were highlighted.
      Thereafter, calibration transfer functions were constructed to show the
      possibility to compare the results obtained during two distinct measurement
      campaigns conducted with two Raman probes of the same conception. This approach
      could lead to several interesting prospects, in particular by objectifying the
      effects of dermocosmetic products on the superficial layers of the skin and by
      accessing some underlying molecular mechanisms. 

PMID- 26297465
TI  - Rapid measurement of perchlorate in polar ice cores down to sub-ng L(-1) levels
      without pre-concentration.
AB  - An ion chromatography-electrospray ionization-tandem mass spectrometry (IC-ESI
      MS/MS) method has been developed for rapid and accurate measurement of
      perchlorate in polar snow and ice core samples in which perchlorate
      concentrations are expected to be as low as 0.1 ng L(-1). Separation of
      perchlorate from major inorganic species in snow is achieved with an ion
      chromatography system interfaced to an AB SCIEX triple quadrupole mass
      spectrometer operating in multiple reaction monitoring mode. Under optimized
      conditions, the limit of detection and lower limit of quantification without pre
      concentration have been determined to be 0.1 and 0.3 ng L(-1), respectively, with
      a linear dynamic range of 0.3-10.0 ng L(-1) in routine measurement. These
      represent improvements over previously reported methods using similar analytical
      techniques. The improved method allows fast, accurate, and reproducible
      perchlorate quantification down to the sub-ng L(-1) level and will facilitate
      perchlorate measurement in the study of natural perchlorate production with polar
      ice cores in which perchlorate concentrations are anticipated to vary in the low
      and sub-ng L(-1) range. Initial measurements of perchlorate in ice core samples
      from central Greenland show that typical perchlorate concentrations in snow dated
      prior to the Industrial Revolution are about 0.8 ng L(-1), while perchlorate
      concentrations are significantly higher in recent (post-1980) snow, suggesting
      that anthropogenic sources are a significant contributor to perchlorate in the
      current environment. 

PMID- 26297466
TI  - Time-resolved spectroscopy of a homogeneous dielectric barrier discharge for soft
      ionization driven by square wave high voltage.
AB  - Helium capillary dielectric barrier discharge driven by the square wave-shaped
      high voltage was investigated spatially and temporally by means of optical
      emission spectroscopy. The finding of the previous investigation conducted with
      the sinusoidal-like high voltage was confirmed, i.e., the plasma in the jet and
      the plasma in the capillary constitute two temporally separated events. The
      plasma in the jet occurs prior to the discharge in the capillary and exists only
      during the positive half period of the applied high voltage. The time delay of
      the capillary discharge with respect to the discharge in the jet depended on the
      high voltage, and it was between 2.4 and 8.4 MUs for the voltage amplitude change
      in the range from 1.96 to 2.31 kV, respectively. It was found that, compared to
      sinusoidal-like voltage, application of the square wave high voltage results with
      stronger (~6 times) He line emission in the jet, which makes the latter more
      favorable for efficient soft ionization. The use of the square wave high voltage
      enabled comparison of the currents (~1 mA) flowing in the capillary during the
      positive and negative high voltage periods, which yielded the estimation for the
      charge dissipated in the atmosphere ((4 +/- 20 %) * 10(-11) C) through the plasma
      jet. 

PMID- 26297467
TI  - A new social-family model for eating disorders: A European multicentre project
      using a case-control design.
AB  - OBJECTIVE: To examine a new socio-family risk model of Eating Disorders (EDs)
      using path-analyses. METHOD: The sample comprised 1264 (ED patients = 653;
      Healthy Controls = 611) participants, recruited into a multicentre European
      project. Socio-family factors assessed included: perceived maternal and parental
      parenting styles, family, peer and media influences, and body dissatisfaction.
      Two types of path-analyses were run to assess the socio-family model: 1.) a
      multinomial logistic path-model including ED sub-types [Anorexia Nervosa
      Restrictive (AN-R), AN-Binge-Purging (AN-BP), Bulimia Nervosa (BN) and EDNOS)] as
      the key polychotomous categorical outcome and 2.) a path-model assessing whether
      the socio-family model differed across ED sub-types and healthy controls using
      body dissatisfaction as the outcome variable. RESULTS: The first path-analyses
      suggested that family and media (but not peers) were directly and indirectly
      associated (through body dissatisfaction) with all ED sub-types. There was a weak
      effect of perceived parenting directly on ED sub-types and indirectly through
      family influences and body dissatisfaction. For the second path-analyses, the
      socio-family model varied substantially across ED sub-types. Family and media
      influences were related to body dissatisfaction in the EDNOS and control sample,
      whereas perceived abusive parenting was related to AN-BP and BN. DISCUSSION: This
      is the first study providing support for this new socio-family model, which
      differed across ED sub-types. This suggests that prevention and early
      intervention might need to be tailored to diagnosis-specific ED profiles.

PMID- 26297468
TI  - The nutritional status and energy and protein intakes of MOW clients and the need
      for further targeted strategies to enhance intakes.
AB  - There is a paucity of literature about the nutritional status and energy and
      protein intakes of Meals on Wheels (MOW) clients. The current study aimed to
      determine the nutritional status and the adequacy of energy and protein intakes
      of MOW clients. Forty-two clients were recruited from two MOW services in the
      Illawarra region of Australia for assessment of their nutritional status, using
      the Mini Nutritional Assessment (MNA((r))). Estimated energy and protein intakes
      for a MOW day were compared to a non-MOW day and average daily energy and protein
      intakes were assessed against estimated daily requirements. A single dietitian
      performed all assessments and home based interviews to explore the client's
      perception of the service. Mean daily energy intake (7593 (+/-2012) kJ) was not
      significantly different to estimated requirements (7720 (+/-975) kJ) (P = 0.480),
      while mean daily protein intake was higher (78.7 (+/-23.4) g) than calculated
      requirements (68.4 (+/-10.8) g; P = 0.009). However 16 clients were identified as
      at risk of malnutrition and 2 were malnourished; consuming 2072 kJ (P = 0.000)
      less energy and 20.4 g less protein (P = 0.004) per day compared to well
      nourished clients. MOW clients are at risk of being poorly nourished and meals
      delivered by the service provide an important contribution to overall intakes.
      These findings support the need for regular nutrition screening and dietary
      monitoring in this high risk group, to identify those for whom additional
      strategies may be indicated.

PMID- 26297469
TI  - How to use local resources to fight malnutrition in Madagascar? A study combining
      a survey and a consumer test.
AB  - This study aimed to understand consumers' habits and belief structures concerning
      local food products and to develop a new snack as a way to fight against children
      malnutrition in Madagascar. A large variety of natural food resources grow in
      Madagascar, like Moringa oleifera (MO) which leaves are rich in nutrients but not
      consumed. First, a survey conducted in four areas of Madagascar revealed that MO
      leaves are known for their health benefits but infrequently consumed, probably
      because of their low satiating power and strong odor. In the studied areas,
      different levels of consumption were observed, which may be linked to varying
      levels of familiarity with MO by the local populations, this in turn resulting
      from different situations regarding geographical and historical availability. In
      contrary, resources such as cassava are perceived as having negative effects on
      health but are widely consumed because they are cheap, liked by children and
      satiating. The second step in the study aimed to propose products that could
      increase MO consumption without completely changing food practices. The
      acceptability of snacks associating cassava roots and MO was evaluated by means
      of hedonic tests performed by children. Between the snacks tested, the preferred
      snack contained the highest quantity of MO and was sweetened. There was no effect
      of area on the acceptance of the formulated snacks. This work is an evaluation of
      the potential of MO in the diet of malnourished population. 

PMID- 26297470
TI  - Impact of NIHR HTA Programme funded research on NICE clinical guidelines: a
      retrospective cohort.
AB  - BACKGROUND: It is vitally important that there is a connection between health
      research and clinical practice. Indications as to the impact of the research on
      evidence-based practice and policy can be obtained by tracking the use of outputs
      of health research, especially its use in clinical guidelines (CGs). This study
      aims to assess the proportion of National Institute for Health and Care
      Excellence (NICE) CGs citing National Institute for Health Research Health
      Technology Assessment (NIHR HTA) studies and the impact of evidence from those
      studies on the included NICE CGs. METHODS: This is a retrospective cohort study
      assessing the proportion of NICE CGs from all NICE CGs issued between April 2001
      and April 2012, which cited evidence from studies funded by the NIHR HTA
      Programme and the impact of those studies on the CGs as the primary and secondary
      outcome measures. RESULTS: Of the cohort of NICE CGs (n = 122), 3 (2%) CGs were
      based on previous NIHR HTA reports and would not have been issued in that form
      without those NIHR HTA studies, 90 (74%) included evidence from NIHR HTA studies,
      and 29 (24%) did not include evidence from NIHR HTA studies. The impact of NIHR
      HTA evidence on NICE CGs varied in the type and quantity of data used.
      CONCLUSIONS: Findings suggest that NIHR HTA funded research impacts on clinical
      guidance from NICE and hence is well connected to both clinical practice and
      policy.

PMID- 26297471
TI  - An assessment of horse (Equus ferus caballus) responding on fixed interval
      schedules of reinforcement: An individual analysis.
AB  - We assessed different measures of temporal control of horse (N=16) responding on
      fixed interval schedules of reinforcement and a peak procedure. Subjects were
      trained to insert their heads into a response hoop to break an infrared beam in
      order to receive horse treats from an automatic feeder. We analyzed cumulative
      response records, binned response levels, quarter life, latency to first
      response, breakpoint, and inter-response patterns of the fixed interval trials.
      To analyze the peak procedure trials, we performed a series of bin analyses. To
      avoid potential pitfalls associated with aggregate analyses, we performed
      individual trial and subject analyses using an ordinal analysis within
      Observation Oriented Modeling. Most subjects produced clear indications that
      responding came under temporal control of the fixed interval schedules for most
      of our investigated measures, and some subjects' response levels peaked at half
      of the peak trial intervals. We provide the first quantitative evidence of equine
      timing performances using protocols based on fixed interval schedules of
      reinforcement. 

PMID- 26297472
TI  - The group I pilin glycan affects type IVa pilus hydrophobicity and twitching
      motility in Pseudomonas aeruginosa 1244.
AB  - The group I pilin category is the most common type of type IVa pilus produced by
      Pseudomonas aeruginosa. The lateral surfaces of these pili are characterized by
      the presence of closely spaced, covalently attached O-antigen repeating units.
      The current work was conducted to investigate the pilin glycan's effect on pilus
      solubility and function. Culture supernatant fluids containing fully, partially
      and non-glycosylated P. aeruginosa group I pili were tested for solubility in the
      presence of ammonium sulfate. These results showed that while pili expressing
      three or four sugars were highly soluble under all conditions, those with fewer
      than three were insoluble under the lowest salt concentrations tested. A
      representative of the P. aeruginosa group II pili also showed low solubility when
      assayed under these same conditions. Reduced solubility suggested an increased
      pilus surface hydrophobicity, which was supported by protein modelling. While
      having no effect on the WT strain, an ionic strength found at many host infection
      sites inhibited surface and subsurface twitching motility of strain 1244G7, an
      isogenic mutant unable to glycosylate pilin. This effect was reversed by mutant
      complementation. Twitching motility of P. aeruginosa strain PA103, which produces
      group II pili, was also inhibited by ionic strengths which influenced the mutant
      1244 strain. We suggest that the group I pilin glycan may, therefore, be
      beneficial to this organism specifically for optimal pilus functioning at the
      many host disease sites with ionic strengths comparable to those tested here. 

PMID- 26297473
TI  - Facial, vocal and cross-modal emotion processing in early-onset schizophrenia
      spectrum disorders.
AB  - Recognition of emotional expressions plays an essential role in children's
      healthy development. Anomalies in these skills may result in empathy deficits,
      social interaction difficulties and premorbid emotional problems in children and
      adolescents with schizophrenia. Twenty-six subjects with early onset
      schizophrenia spectrum (EOSS) disorders and twenty-eight matched healthy controls
      (HC) were instructed to identify five basic emotions and a neutral expression.
      The assessment entailed presenting visual, auditory and congruent cross-modal
      stimuli. Using a generalized linear mixed model, we found no significant
      association for handedness, age or gender. However, significant associations
      emerged for emotion type, perception modality, and group. EOSS patients performed
      worse than HC in uni- and cross-modal emotional tasks with a specific negative
      emotion processing impairment pattern. There was no relationship between emotion
      identification scores and positive or negative symptoms, self-reported empathy
      traits or a positive history of developmental disorders. However, we found a
      significant association between emotional identification scores and nonverbal
      communication impairments. We conclude that cumulative dysfunctions in both
      nonverbal communication and emotion processing contribute to the social
      vulnerability and morbidity found in youths who display EOSS disorder. 

PMID- 26297474
TI  - Nurses' knowledge, attitudes, and current practice of daily oral hygiene care to
      patients on acute aged care wards in two Australian hospitals.
AB  - This study aimed to identify nurses' knowledge, attitudes, and current practice
      in relation to oral hygiene (OH) by means of a questionnaire. It was conducted on
      the aged care wards of two acute tertiary referral hospitals in New South Wales,
      Australia. We found that 74% of nurses have a set OH practice. Fifty-four percent
      of nurses learn their OH practice at university or TAFE. The main nurse
      qualification is a registered nurse (72%). Denture cleaning, toothbrushing, and
      swabbing the mouth with a toothette are the main OH practices. Nurses (99%)
      considered OH to be important. The main barriers to conducting OH practices were
      patient behaviors, lack of time and staff, and patient physical difficulties.
      Nurses considered OH important however patient behaviors impact on their ability
      to undertake the task. Education institutions and hospitals should consider the
      joint development of a formal OH procedure and training package that can be used
      on acute geriatric care wards. 

PMID- 26297475
TI  - High levels of fish oil enhance neutrophil development and activation and
      influence colon mucus barrier function in a genetically susceptible mouse model.
AB  - Dietary fatty acids influence immunologic homeostasis, but their effect on
      initiation of colitis, an immune-mediated disease, is not well established.
      Previously, our laboratory demonstrated that high doses of dietary fish oil (FO)
      increased colon inflammation and dysplasia in a model of infection-induced
      colitis. In the current study, we assessed the effects of high-dose dietary FO,
      6% by weight, on colon inflammation, neutrophil recruitment and function, and
      mucus layer integrity in a genetically susceptible, colitis-prone mouse model in
      the absence of infection. FO-fed SMAD3(-/-) mice had increased colon inflammation
      evidenced by increased numbers of systemic and local neutrophils and increased
      neutrophil chemoattractant and inflammatory cytokine gene expression in the
      colon. Mucus layer thickness in the cecum and goblet cell numbers in the cecum
      and colon in FO-fed mice were reduced compared to control. FO consumption
      affected colitis in male and female mice differently. Compared to female control
      mice, neutrophils from FO-fed female mice had reduced reactive oxygen species
      (ROS) upon ex vivo stimulation with phorbol myristate acetate while FO-fed male
      mice produced increased ROS compared to control-fed male mice. In summary,
      dietary FO impaired mucus layer integrity and was associated with colon
      inflammation characterized by increased neutrophil numbers and altered neutrophil
      function. High-dose FO may have detrimental effects in populations genetically
      susceptible for inflammatory bowel disease and these effects may differ between
      males and females. 

PMID- 26297476
TI  - Inhibition of tumor progression by oral piceatannol in mouse 4T1 mammary cancer
      is associated with decreased angiogenesis and macrophage infiltration.
AB  - Piceatannol, a polyphenol which exhibits anticancer activities, is found in
      grapes, red wine and berries. It has been shown to inhibit several transcription
      factor pathways. The present study was conducted to determine whether oral
      administration of piceatannol inhibits mammary tumor progression. 4T1 mammary
      carcinoma cells were injected into the mammary fat pad of syngeneic female BALB/c
      mice. Starting 1 day later, piceatannol (10- or 20-mg/kg body weight/day) was
      administered by oral gavage for 30 days. Piceatannol treatment reduced tumor
      growth. In tumor tissues, piceatannol treatment reduced the expression of
      transcription factors P-NFkappaB p65, P-STAT3 and HIF-1alpha and multiple
      proteins involved in regulation of cell cycle progression (Ki67, cyclin D1,
      cyclin A, CDK2, CDK4), angiogenesis (VEGF-A, VEGFR-2, VE-cadherin, CD31) and
      lymphangiogenesis (VEGF-C, LYVE-1), as well as macrophage infiltration.
      Piceatannol significantly increased apoptotic cells and expression of both Bax
      and cleaved caspase-3 but reduced Bcl-2 expression in tumor tissues. In addition,
      piceatannol reduced the number and volume of pulmonary tumor nodules and
      expression of MMP-9 in both lung and tumor. It also reduced tissue levels of
      cytokines/chemokines, including M-CSF and MCP-1. In vitro results revealed that
      piceatannol inhibited migration of 4T1 cells and monocytes, as well as secretion
      of MCP-1 and M-CSF by 4T1 cells. 4T1 cell-conditioned medium stimulated monocyte
      migration, which was suppressed by a CCR2 antibody. These results indicate that
      alteration in tumor microenvironment (macrophages, transcription factors, etc.)
      is an important mechanism by which piceatannol inhibits tumor proliferation,
      angiogenesis and lymphangiogenesis, leading to suppression of mammary tumor
      growth and metastasis. 

PMID- 26297477
TI  - Zebra finches are able to learn affixation-like patterns.
AB  - Adding an affix to transform a word is common across the world languages, with
      the edges of words more likely to carry out such a function. However, detecting
      affixation patterns is also observed in learning tasks outside the domain of
      language, suggesting that the underlying mechanism from which affixation patterns
      have arisen may not be language or even human specific. We addressed whether a
      songbird, the zebra finch, is able to discriminate between, and generalize,
      affixation-like patterns. Zebra finches were trained and tested in a Go/Nogo
      paradigm to discriminate artificial song element sequences resembling prefixed
      and suffixed 'words.' The 'stems' of the 'words,' consisted of different
      combinations of a triplet of song elements, to which a fourth element was added
      as either a 'prefix' or a 'suffix.' After training, the birds were tested with
      novel stems, consisting of either rearranged familiar element types or novel
      element types. The birds were able to generalize the affixation patterns to novel
      stems with both familiar and novel element types. Hence, the discrimination
      resulting from the training was not based on memorization of individual stimuli,
      but on a shared property among Go or Nogo stimuli, i.e., affixation patterns.
      Remarkably, birds trained with suffixation as Go pattern showed clear evidence of
      using both prefix and suffix, while those trained with the prefix as the Go
      stimulus used primarily the prefix. This finding illustrates that an asymmetry in
      attending to different affixations is not restricted to human languages. 

PMID- 26297478
TI  - Terrisporobacter petrolearius sp. nov., isolated from an oilfield petroleum
      reservoir.
AB  - A Gram-staining-positive, spore-forming, strictly anaerobic bacterium, designated
      strain LAM0A37T, was isolated from enrichment samples collected from a petroleum
      reservoir in Shengli oilfield. Cells of strain LAM0A37T were rod-shaped and
      motile by peritrichous flagella. The optimal temperature and pH for growth were
      40  degrees C and 7.0-7.5, respectively. The strain did not require NaCl for
      growth but tolerated up to 3 % (w/v) NaCl. Strain LAM0A37T was able to utilize
      glucose, fructose, maltose, xylose, sorbitol, cellobiose, melibiose and
      melezitose as sole carbon sources. Sulfite was used as an electron acceptor. The
      main products of glucose fermentation were acetate and CO2. The predominant fatty
      acid was C16 : 0 (23.6 %). The main polar lipid profile comprised of five
      glycolipids, six phospholipids and two lipids. No menaquinone was detected. The
      genomic DNA G+C content was 27.1 +/- 0.2 mol% as determined by the T m method.
      Analysis of the 16S rRNA gene sequence indicated that the isolate was a member of
      the genus Terrisporobacter, and was most closely related to Terrisporobacter
      glycolicus JCM 1401T and Terrisporobacter mayombei DSM 6539T with 98.3 % 16S rRNA
      gene sequence similarity to both. DNA-DNA hybridization values between strain
      LAM0A37T and type strains of Terrisporobacter glycolicus and Terrisporobacter
      mayombei were 45.6 +/- 0.3 % and 38.3 +/- 0.4 %, respectively. Based on
      phenotypic, phylogenetic and chemotaxonomic characteristics, strain LAM0A37T is
      suggested to represent a novel species of the genus Terrisporobacter, for which
      the name Terrisporobacter petrolearius sp. nov. is proposed. The type strain is
      LAM0A37T ( = ACCC 00740T = JCM 19845T).

PMID- 26297479
TI  - Productive global health research from Africa: it takes more.

PMID- 26297480
TI  - Esophageal Bypass Using a Y-Shaped Gastric Tube for Advanced Esophageal Cancer:
      Transabdominal Placement of the Decompression Tube.

PMID- 26297481
TI  - Defining equivalence in medical education evaluation and research: does a
      distribution-based approach work?
AB  - Educators often seek to demonstrate the equivalence of groups, such as whether or
      not students achieve comparable success regardless of the site at which they
      trained. A methodological consideration that is often underappreciated is how to
      operationalize equivalence. This study examined whether a distribution-based
      approach, based on effect size, can identify an appropriate equivalence threshold
      for medical education data. Thirty-nine individuals rated program site
      equivalence on a series of simulated pairwise bar graphs representing one of four
      measures with which they had prior experience: (1) undergraduate academic
      achievement, (2) a student experience survey, (3) an Objective Structured
      Clinical Exam global rating scale, or (4) a licensing exam. Descriptive
      statistics and repeated measures ANOVA examined the effects on equivalence
      ratings of (a) the difference between means, (b) variability in scores, and (c)
      which program site (the larger or smaller) scored higher. The equivalence
      threshold was defined as the point at which 50 % of participants rated the sites
      as non-equivalent. Across the four measures, the equivalence thresholds converged
      to average effect size of Cohen's d = 0.57 (range of 0.50-0.63). This
      corresponded to an average mean difference of 10 % (range of 3-13 %). These
      results are discussed in reference to findings from the health-related quality of
      life field that has demonstrated that d = 0.50 represents a consistent threshold
      for perceived change. This study provides preliminary empirically-based guidance
      for defining an equivalence threshold for researchers and evaluators conducting
      equivalence tests.

PMID- 26297482
TI  - Maritimibacter lacisalsi sp. nov., isolated from a salt lake, and emended
      description of the genus Maritimibacter Lee et al. 2007.
AB  - A Gram-staining-negative, non-motile, strictly aerobic bacterium, strain X12M-4T,
      was isolated from Xiaochaidan Lake, a salt lake (salinity 9.9 %, w/w) in Qaidam
      basin, Qinghai Province, China. Its taxonomic position was determined by using a
      polyphasic approach. Strain X12M-4T was catalase- and oxidase-positive. Cells
      were rod-shaped, 0.5-0.8 MUm wide and 1.1-1.6 MUm long. Growth was observed in
      the presence of 0-11.0 % (w/v) NaCl (optimum, 5.0-6.0 %) and at 15-40  degrees C
      (optimum, 25  degrees C) and pH 6.5-9.5 (optimum, pH 7.0). No growth occurred at
      10  degrees C or 45  degrees C. Strain X12M-4T contained C18 : 1omega7c, C19 : 0
      cyclo omega8c and C16 : 0 as the major fatty acids (>10.0 %). The predominant
      respiratory quinone was Q-10.The major polar lipids were phosphatidylcholine,
      phosphatidylglycerol, diphosphatidglycerol, an unknown aminolipid and an
      unidentified lipid. The DNA G+C content was 65.7 mol% (determined using T m).
      Strain X12M-4T showed highest 16S rRNA gene sequence similarities to
      Maritimibacter alkaliphilus HTCC2654T (96.7 %), Roseibacterium elongatum DSM
      19469T (96.4 %), Tropicimonas aquimaris DPG-21T (95.6 %), 'Roseibacterium
      beibuensis' JLT1202r (95.6 %) and Tropicimonas sediminicola M97T (95.5 %) and <
      95.5 % to others. Phylogenetic trees based on 16S rRNA gene sequences indicated
      that strain X12M-4T formed a robust cluster with M. alkaliphilus HTCC2654T. On
      the basis of the data, it is concluded that strain X12M-4T represents a novel
      species of the genus Maritimibacter, for which the name Maritimibacter lacisalsi
      sp. nov. is proposed. The type strain is X12M-4T ( = CGMCC 1.12922T = JCM
      30555T). To accommodate the novel species, the description of the genus
      Maritimibacter was emended.

PMID- 26297483
TI  - Patient Safety Perceptions in Pediatric Out-of-Hospital Emergency Care:
      Children's Safety Initiative.
AB  - OBJECTIVE: To characterize emergency medical service (EMS) providers' perceptions
      of the factors that contribute to safety events and errors in the out-of-hospital
      emergency care of children. STUDY DESIGN: We used a Delphi process to achieve
      consensus in a national sample of 753 emergency medicine physicians and EMS
      professionals. Convergence and stability were achieved in 3 rounds, and findings
      were reviewed and interpreted by a national expert panel. RESULTS: Forty-four
      (88%) states were represented, and 66% of participants were retained through all
      3 rounds. From an initial set of 150 potential contributing factors derived from
      focus groups and literature, participants achieved consensus on the following
      leading contributors: airway management, heightened anxiety caring for children,
      lack of pediatric skill proficiency, lack of experience with pediatric equipment,
      and family members leading to delays or interference with care. Somewhat
      unexpectedly, medications and communication were low-ranking concerns. After
      thematic analysis, the overarching domains were ranked by their relative
      importance: (1) clinical assessment; (2) training; (3) clinical decision-making;
      (4) equipment; (5) medications; (6) scene characteristics; and (7) EMS cultural
      norms. CONCLUSIONS: These findings raise considerations for quality improvement
      and suggest important roles for pediatricians and pediatric emergency physicians
      in training, medical oversight, and policy development.

PMID- 26297484
TI  - A systematic review of variations of the recurrent laryngeal nerve.
AB  - With thyroid cancer fast becoming one of the most common endocrine cancers, the
      frequency of thyroid surgery has increased. A common and debilitating concern
      with thyroid surgery is recurrent laryngeal nerve (RLN) paralysis leading to
      glottal obstruction and airway compromise. A systematic review regarding the
      anatomical variation of the recurrent laryngeal nerve was performed to determine
      the position of anatomical variants of the RLN in relation to the inferior
      thyroid artery (ITA) as well as the prevalence of nonrecurrent laryngeal nerve
      (NRLN). MEDLINE, Web of Science, MEDITEXT, AMED, CINAHL, Cochrane, ProQuest,
      Pubmed, and ScienceDirect. Databases were searched using the search terms
      "inferior thyroid artery," "recurrent laryngeal nerve," "nonrecurrent laryngeal
      nerve," and "anatomical variation." The reference sections of the articles found
      were searched for additional reports. The references of all articles were
      searched to find articles missed in the database search. A total of 8,655 RLN
      sides were included in this study. One thousand eight hundred and thirteen
      (20.95%; 95% confidence interval (CI) 20.09, 2,182) showed a Type A configuration
      of RLN in relation to the ITA, 2,432 (28.10%; 95% CI 27.15, 29.06) showed a Type
      B configuration and 4,410 (50.95%; 95% CI 49.89, 52.01) showed a Type C
      configuration between the RLN and the ITA. The second search returned with 38,568
      recurrent laryngeal sides and only 221 (0.57%; 95%CI 0.5, 0.65) NRLN documented.
      The RLN is most commonly found in the posterior position, relative to the ITA.
      The incidence of the NRLN is low, only occurring in 0.57% of people.

PMID- 26297485
TI  - The beneficial effect of Zinc(II) on low-dose chemotherapeutic sensitivity
      involves p53 activation in wild-type p53-carrying colorectal cancer cells.
AB  - BACKGROUND: Activation of wild-type p53 in response to genotoxic stress occurs
      through different mechanisms including protein conformation, posttranslational
      modifications, and nuclear localization, leading to DNA binding to sequence
      specific promoters. Zinc ion plays a crucial role in stabilizing p53/DNA binding
      to induce canonical target genes. Mutant p53 proteins undergo protein misfolding
      that can be counteracted by zinc. However, whether zinc supplementation might
      have a beneficial antitumor effect in wild-type p53-carrying cells in combination
      with drugs, has not been addressed so far. METHODS: In this study we compared the
      effect of two antitumor treatments: on the one hand wild-type p53-carrying colon
      cancer cells were treated with low and high doses of chemotherapeutic agent
      Adriamycin and, on the other hand, Adriamycin was used in combination with ZnCl2.
      Biochemical and molecular analyses were applied to evaluate p53 activity and
      biological outcomes in this setting. Finally, the effect of the different
      combination treatments were applied to assess tumor growth in vivo in tumor
      xenografts. RESULTS: We found that low-dose Adriamycin did not induce p53
      activation in wtp53-carrying colon cancer cells, unless in combination with
      ZnCl2. Mechanistically, ZnCl2 was a key determinant in inducing wtp53/DNA binding
      and transactivation of target genes in response to low-dose Adriamycin that used
      alone did not achieve such effects. Finally, in vivo studies, in a model of wtp53
      colon cancer xenograft, show that low-dose Adriamycin did not induce tumor
      regression unless in combination with ZnCl2 that activated endogenous wtp53.
      CONCLUSIONS: These results provide evidence that ZnCl2 might be a valuable
      adjuvant in chemotherapeutic regimens of colorectal cancer harboring wild-type
      p53, able to both activate p53 and reduce the amount of drugs for antitumor
      purposes.

PMID- 26297487
TI  - Streptomyces rubrisoli sp. nov., neutrotolerant acidophilic actinomycetes
      isolated from red soil.
AB  - Three neutrotolerant, acidophilic actinomycete strains, designated FXJ1.526,
      FXJ1.725(T) and FXJ1.726, were isolated from red soil collected from Liujiazhan,
      Jiangxi Province, China. Phylogenetic analysis based on 16S rRNA gene sequences
      indicated that the three strains clustered together and their closest relative
      was Streptomyces ferralitis CGMCC 4.1985(T) (98.9-99.0% similarity). Multilocus
      sequence analysis confirmed their relationship to S. ferralitis and separated
      these strains as representing a novel species. Mean DNA-DNA hybridization values
      among strains FXJ1.526, FXJ1.725(T) and FXJ1.726 were 81.6 +/- 3.5-87.2 +/- 3.8%,
      and the values between the three strains and S. ferralitis CGMCC 4.1985(T) were
      well below 70%. The three strains also shared several phenotypic characteristics
      that were distinct from the closely related species. They grew at 21-50  degrees
      C, at pH 4.0-9.0 (with an optimal pH of 5.0) and with 0-3% (w/v) NaCl, and the
      major cellular fatty acids were anteiso-C15 : 0, iso-C15 : 0 and iso-C16 : 0. On
      the basis of data from this polyphasic taxonomic study, it is proposed that
      strains FXJ1.526, FXJ1.725(T) and FXJ1.726 be classified as representatives of a
      novel species of the genus Streptomyces, with the name Streptomyces rubrisoli sp.
      nov. The type strain is FXJ1.725(T) ( = CGMCC 4.7025(T)= DSM 42083(T)).

PMID- 26297486
TI  - Integrative analysis of RNA, translation, and protein levels reveals distinct
      regulatory variation across humans.
AB  - Elucidating the consequences of genetic differences between humans is essential
      for understanding phenotypic diversity and personalized medicine. Although
      variation in RNA levels, transcription factor binding, and chromatin have been
      explored, little is known about global variation in translation and its genetic
      determinants. We used ribosome profiling, RNA sequencing, and mass spectrometry
      to perform an integrated analysis in lymphoblastoid cell lines from a diverse
      group of individuals. We find significant differences in RNA, translation, and
      protein levels suggesting diverse mechanisms of personalized gene expression
      control. Combined analysis of RNA expression and ribosome occupancy improves the
      identification of individual protein level differences. Finally, we identify
      genetic differences that specifically modulate ribosome occupancy--many of these
      differences lie close to start codons and upstream ORFs. Our results reveal a new
      level of gene expression variation among humans and indicate that genetic
      variants can cause changes in protein levels through effects on translation.

PMID- 26297488
TI  - Sentinel events predicting later unwanted sex among girls: A national survey in
      Haiti, 2012.
AB  - Sexual violence against children is a significant global public health problem,
      yet limited studies exist from low-resource settings. In Haiti we conducted the
      country's first, nationally representative survey focused on childhood violence
      to help inform the development of a national action plan for violence against
      children. The Haiti Violence Against Children Survey was a household-level,
      multistage, cluster survey among youth age 13-24. In this analysis we sought to
      determine whether sexual violence sentinel events (unwanted sexual touching or
      unwanted attempted sex) were predictive of later unwanted, completed, penetrative
      sex in Haiti. We also sought to explore characteristics of sentinel events and
      help-seeking behavior among Haitian children. Multivariable logistic regression
      was used to test associations between sentinel events and later unwanted,
      completed, penetrative sex. Overall, 1,457 females reported on experiences of
      sexual violence occurring in childhood (before age 18). A sentinel event occurred
      in 40.4% of females who experienced subsequent unwanted completed sex. Females
      experiencing a sentinel event were approximately two and a half times more likely
      to experience later unwanted completed sex (adjusted odds ratio=2.40, p=.004)
      compared to individuals who did not experience a sentinel event. The mean lag
      time from first sentinel event to first unwanted completed sex was 2.3 years.
      Only half (54.6%) of children experiencing a sentinel event told someone about
      their experience of sexual violence. Among children, sentinel events occur
      frequently before later acts of completed unwanted sex and may represent a useful
      point of intervention. Reporting of sexual violence by children in Haiti is low
      and can be improved to better act on sentinel events.

PMID- 26297489
TI  - Oxidative stress in Nipah virus-infected human small airway epithelial cells.
AB  - Nipah virus (NiV) is a zoonotic emerging pathogen that can cause severe and often
      fatal respiratory disease in humans. The pathogenesis of NiV infection of the
      human respiratory tract remains unknown. Reactive oxygen species (ROS) produced
      by airway epithelial cells in response to viral infections contribute to lung
      injury by inducing inflammation and oxidative stress; however, the role of ROS in
      NiV-induced respiratory disease is unknown. To investigate whether NiV induces
      oxidative stress in human respiratory epithelial cells, we used oxidative stress
      markers and monitored antioxidant gene expression. We also used ROS scavengers to
      assess their role in immune response modulation. Oxidative stress was confirmed
      in infected cells and correlated with the reduction in antioxidant enzyme gene
      expression. Infected cells treated by ROS scavengers resulted in a significant
      decrease of the (F2)-8-isoprostane marker, inflammatory responses and virus
      replication. In conclusion, ROS are induced during NiV infection in human
      respiratory epithelium and contribute to the inflammatory response. Understanding
      how oxidative stress contributes to NiV pathogenesis is crucial for therapeutic
      development. 

PMID- 26297490
TI  - Pre-vaccination type-specific HPV prevalence in confirmed cervical high grade
      lesions in the Maori and non-Maori populations in New Zealand.
AB  - BACKGROUND: New Zealand initiated HPV vaccination in 2008, and has attained 3
      dose coverage of ~50 % in 12-13 year old girls. Due to the success of program
      initiatives in Maori girls, higher coverage rates of ~60 % have been achieved in
      this group. We have previously reported a benchmark overall pre-vaccination
      prevalence of oncogenic HPV infection in high grade cervical lesions in New
      Zealand. The current extended analysis provides separate pre-vaccination
      benchmark prevalence for Maori and non-Maori women. METHODS: The National
      Cervical Screening Programme Register (NCSP-R) was used to identify any woman
      aged 20-69 years of age with an index high grade cytology report from 2009-2011.
      Extended recruitment was performed until 2012 in clinics with a high proportion
      of Maori women. Ethnicity status was based on self-reported information by
      participating women through phone contact supplemented by recordings on the study
      questionnaire (the NCSP-R was not used to extract ethnicity status). A total of
      730 women consented to participate and had a valid HPV test result; 418 of these
      had histologically-confirmed cervical intraepithelial neoplasia (CIN) 2/3 lesions
      (149 Maori, 269 non-Maori). The prevalence of any cervical oncogenic HPV
      infection, HPV16, and HPV18 was calculated in women with CIN2/3. RESULTS: In
      confirmed CIN2/3, the prevalence of any oncogenic HPV, HPV16 and HPV18 was 96 %
      (95 % CI:91-99 %), 54 % (95 % CI:46-63 %), 11 % (95 % CI:7-18 %) in Maori and 96
      % (95 % CI:93-98 %), 54 % (95 % CI:48-60 %), 11 % (95 % CI:7-15 %) in non-Maori
      women, respectively. Age-specific patterns of infection for HPV16/18 in confirmed
      CIN2/3 differed between the two groups (Pinteraction = 0.02), with a lower
      prevalence in younger vs. older Maori women (57 % in 20-29 years vs 75 % in 40-69
      years) but a higher prevalence in younger vs. older non-Maori women (70 % in 20
      29 years vs 49 % in 40-69 years); the difference in the age-specific patterns of
      infection for HPV16/18 was not significant either when considering confirmed CIN2
      alone (p = 0.09) or CIN3 alone (p = 0.22). CONCLUSIONS: The overall prevalence of
      vaccine-included types in CIN2/3 was similar in Maori and non-Maori women,
      implying that the long-term effects of vaccination will be similar in the two
      groups.

PMID- 26297491
TI  - Terriglobus albidus sp. nov., a member of the family Acidobacteriaceae isolated
      from Namibian semiarid savannah soil.
AB  - A novel aerobic, chemo-organoheterotrophic bacterium, strain Ac_26_B10T, was
      isolated from a semiarid savannah soil collected in northern Namibia (Mashare,
      Kavango region). Based on analysis of its nearly full-length 16S rRNA gene
      sequence, the isolate belongs to the genus Terriglobus (family Acidobacteriaceae,
      order Acidobacteriales, class Acidobacteria) and shares 98.3 and 96.9 % 16S rRNA
      gene sequence similarity with its closest relatives, Terriglobus tenax DRP 35T
      and T. aquaticus O3SUJ4T. Cells were Gram-negative, coccoid to rod-shaped, non
      motile and divided by binary fission. Strain Ac_26_B10T showed weak catalase
      activity and, in contrast to the other described species of the genus
      Terriglobus, was oxidase-positive. Compared with the already established species
      of the genus Terriglobus, the novel strain used a larger range of sugars and
      sugar alcohols for growth, lacked alpha-mannosidase activity and exhibited a
      higher temperature optimum of growth. DNA-DNA hybridization studies with its
      closest phylogenetic relative, T. tenax DSM 28898T, confirmed that strain
      Ac_26_B10T represents a distinct genomospecies. Its most abundant fatty acids
      were iso-C15 : 0, summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c) and C16
      : 0. Dominant polar lipids were phosphatidylethanolamine and
      diphosphatidylglycerol. The predominant menaquinone was MK-8; minor amounts of MK
      7 and MK-8(H2) were also recorded. The G+C content of the genomic DNA was 58.5
      mol%. On the basis of our polyphasic analysis, Ac_26_B10T represents a novel
      species of the genus Terriglobus, for which the name Terriglobus albidus sp. nov.
      is proposed. The type strain is Ac_26_B10T ( = DSM 26559T = LMG 27984T).

PMID- 26297492
TI  - Nonadherence is Associated with Lack of HIV-Related Knowledge: A Cross-Sectional
      Study among HIV-Infected Individuals in Guinea-Bissau.
AB  - BACKGROUND: Poor treatment adherence is a main barrier for effective
      antiretroviral therapy (ART) globally. HIV-related knowledge may affect
      understanding and utilization of HIV medical information, hence limited health
      literacy is a known barrier to treatment adherence. DESIGN AND METHODS: A cross
      sectional study included 494 HIV-infected individuals from the Bissau HIV Cohort
      in Guinea-Bissau. They completed a questionnaire designed for assessment of
      adherence and HIV-related knowledge. RESULTS: A majority were female, 41% were
      illiterate, 25% did not take the medicine during the last 4 days, and 23% skipped
      their medicine during weekends. The most frequent reasons for not taking medicine
      were simply forgetting, side effects, lack of food, and being too ill to attend
      the clinic. Nonadherent patients had a lower level of HIV-related knowledge.
      CONCLUSION: Main barriers for nonadherence were side effects, food insecurity,
      and simply forgetting. Lack of HIV-related knowledge about ART and HIV may be a
      barrier to nonadherence.

PMID- 26297493
TI  - Kordia zhangzhouensis sp. nov., isolated from surface freshwater.
AB  - An aerobic, Gram-stain-negative, rod-shaped and non-motile bacterium, JS14SB-1T,
      was isolated from the surface freshwater of the Jiulong River, PR China. Strain
      JS14SB-1T grew at 15-38  degrees C (optimum, 28-35  degrees C), at pH 6.0-9.0
      (optimum pH 7.0) and in the presence of 1.0-7.0 % (w/v) NaCl [optimum 3.0-5.0 %
      (w/v)]. Phylogenetic analysis, based on 16S rRNA gene sequences, indicated that
      strain JS14SB-1T was affiliated to the genus Kordia, sharing low similarities
      (95.1-97.1 %) to all type strains of species of this genus. The digital DNA-DNA
      hybridization (DDH) value between strain JS14SB-1T and the closely related strain
      Kordia jejudonensis SSK3-3T was 20.70 +/- 2.33 % and far below the 70 % DDH value
      taken as the gold standard for delineation of bacterial species. The major fatty
      acids were identified as iso-C15 : 0 and iso-C17 : 0 3-OH. The polar lipids were
      phosphatidylethanolamine, glycolipid, aminolipid, several unidentified
      phospholipids and lipids. The predominant menaquinone was MK-6. The G+C content
      of the genomic DNA was 33.8 mol%. Based on the phenotypic, phylogenetic and
      chemotaxonomic distinctiveness, strain JS14SB-1T is considered to represent a
      novel species of the genus Kordia, for which the name Kordia zhangzhouensis sp.
      nov. is proposed; the type strain is JS14SB-1T ( = MCCC 1A00726T = KCTC 42140T).

PMID- 26297494
TI  - Productive life cycle of adeno-associated virus serotype 2 in the complete
      absence of a conventional polyadenylation signal.
AB  - We showed that WT adeno-associated virus serotype 2 (AAV2) genome devoid of a
      conventional polyadenylation [poly(A)] signal underwent complete genome
      replication, encapsidation and progeny virion production in the presence of
      adenovirus. The infectivity of the progeny virion was also retained. Using
      recombinant AAV2 vectors devoid of a human growth hormone poly(A) signal, we also
      demonstrated that a subset of mRNA transcripts contained the inverted terminal
      repeat (ITR) sequence at the 3' end, which we designated ITR in RNA (ITRR).
      Furthermore, AAV replication (Rep) proteins were able to interact with the ITRR.
      Taken together, our studies suggest a new function of the AAV2 ITR as an RNA
      element to mediate transgene expression from poly(A)-deleted mRNA. 

PMID- 26297495
TI  - MANAGEMENT OF ENDOCRINE DISEASE: Outcome of adrenal sparing surgery in heritable
      pheochromocytoma.
AB  - The management of hereditary pheochromocytoma has drastically evolved in the last
      20 years. Bilateral pheochromocytoma does not increase mortality in MEN2 or von
      Hippel-Lindau (VHL) mutation carriers who are followed regularly, but these
      mutations induce major morbidities if total bilateral adrenalectomy is performed.
      Cortical sparing adrenal surgery may be proposed to avoid definitive adrenal
      insufficiency. The surgical goal is to leave sufficient cortical tissue to avoid
      glucocorticoid replacement therapy. This approach was achieved by the progressive
      experience of minimally invasive surgery via the transperitoneal or
      retroperitoneal route. Cortical sparing adrenal surgery exhibits <5% significant
      recurrence after 10 years of follow-up and normal glucocorticoid function in more
      than 50% of the cases. Therefore, cortical sparing adrenal surgery should be
      systematically considered in the management of all patients with MEN2 or VHL
      hereditary pheochromocytoma. Hereditary pheochromocytoma is a rare disease, and a
      randomized trial comparing cortical sparing vs classical adrenalectomy is
      probably not possible. This lack of data most likely explains why cortical
      sparing surgery has not been adopted in most expert centers that perform at least
      20 procedures per year for the treatment of this disease. This review examined
      recent data to provide insight into the technique, its indications, and the
      results and subsequent follow-up in the management of patients with hereditary
      pheochromocytoma with a special emphasis on MEN2. 

PMID- 26297496
TI  - Readiness Assessment to Improve Program Implementation: Shifting the Lens to
      Optimizing Intervention Design.

PMID- 26297497
TI  - The Impact of Teachers' Modifications of an Evidenced-Based HIV Prevention
      Intervention on Program Outcomes.
AB  - The degree to which evidence-based program outcomes are affected by modifications
      is a significant concern in the implementation of interventions. The ongoing
      national implementation of an evidence-based HIV prevention program targeting
      grade 6 students in The Bahamas [Focus on Youth in The Caribbean (FOYC)] offers
      an opportunity to explore factors associated with teachers' modification of FOYC
      lessons and to examine the impact of types and degrees of modifications on
      student outcomes. Data were collected in 2012 from 155 teachers and 3646 students
      in 77 government elementary schools. Results indicate that teachers taught 16 of
      30 core activities, 24.5 of 46 total activities and 4.7 of 8 sessions. Over one
      half of the teachers made modifications to FOYC core activities; one-fourth of
      the teachers modified 25 % or more core activities that they taught (heavily
      modified FOYC). Omitting core activities was the most common content
      modification, followed by lengthening FOYC lessons with reading, writing
      assignments or role-play games, and shortening core activities or adding
      educational videos. Mixed-effects modeling revealed that omitting core activities
      had negative impacts on all four student outcomes. Shortening core activities and
      adding videos into lessons had negative impacts on HIV/AIDS knowledge and/or
      intention to use condom protection. Heavy modifications (>1/4 core activities)
      were associated with diminished program effectiveness. Heavy modifications and
      omitting or shortening core activities were negatively related to teachers' level
      of implementation. We conclude that poorer student outcomes were associated with
      heavy modifications.

PMID- 26297498
TI  - Higher Childhood Peer Reports of Social Preference Mediates the Impact of the
      Good Behavior Game on Suicide Attempt.
AB  - The Good Behavior Game (GBG) is a universal classroom-based preventive
      intervention directed at reducing early aggressive, disruptive behavior and
      improving children's social adaptation into the classroom. The GBG is one of the
      few universal preventive interventions delivered in early elementary school that
      has been shown to reduce the risk for future suicide attempts. This paper
      addresses one potential mechanism by which the GBG lowers the risk of later
      suicide attempt. In this study, we tested whether the GBG, by facilitating social
      adaptation into the classroom early on, including the level of social preference
      by classmates, thereby lowers future risk of suicide attempts. The measure of
      social adaptation is based on first and second grade peer reports of social
      preference ("which children do you like best?"; "which children don't you
      like?"). As part of the hypothesized meditational model, we examined the
      longitudinal association between childhood peer social preference and the risk of
      future suicide attempt, which has not previously been examined. Data were from an
      epidemiologically based randomized prevention trial, which tested the GBG among
      two consecutive cohorts of first grade children in 19 public schools and 41
      classrooms. Results indicated that peer social preference partially mediated the
      relationship between the GBG and the associated reduction of risk for later
      suicide attempts by adulthood, specifically among children characterized by their
      first grade teacher as highly aggressive, disruptive. These results suggest that
      positive childhood peer relations may partially explain the GBG-associated
      reduction of risk for suicide attempts and may be an important and malleable
      protective factor for future suicide attempt. 

PMID- 26297499
TI  - An Emotion Regulation Intervention to Reduce Risk Behaviors Among at-Risk Early
      Adolescents.
AB  - This study aimed to evaluate an intervention designed to enhance early
      adolescents' emotion regulation skill use and to decrease risk behaviors.
      Adolescents 12 to 14 years old (N = 420; 53 % male) with mental health symptoms
      were referred for participation in either an Emotion Regulation (ER) or Health
      Promotion (HP) intervention consisting of 12 after-school sessions. Participants
      completed baseline and follow-up questionnaires on laptop computers. Using a
      generalized analysis of covariance controlling for baseline scores, participants
      in the ER intervention were less likely to be sexually active and engage in other
      risk behaviors, such as fighting, at the conclusion of the program. Additionally,
      participants in the ER intervention reported greater use of emotion regulation
      strategies and more favorable attitudes toward abstinence. Interventions directly
      targeting emotion regulation may be useful in addressing health risk behaviors of
      adolescents with mental health symptoms.

PMID- 26297501
TI  - Molecular identification of tigecycline- and colistin-resistant carbapenemase
      producing Acinetobacter baumannii from a Greek hospital from 2011 to 2013.
AB  - An alarming increase in the resistance rates of tigecycline and colistin among
      carbapenemase-producing Acinetobacter baumannii recovered from a Greek hospital
      over a 3-year period (2011-2013) was investigated. The antimicrobial resistance
      profiles and carbapenemase gene content were determined for a collection of
      colistin- and/or tigecycline-resistant carbapenemase-producing A. baumannii
      isolates (n = 42), which were recovered consecutively during the study period. A
      gradual increase in the incidence of blaOXA-23 producers was observed from 2011
      to 2013. A cluster of 21 isolates comprised tigecycline-resistant blaOXA-23
      producers displayed a single antimicrobial resistance pattern. The emergence of
      two blaOXA-23 producers resistant to both tigecycline and colistin was
      documented. Furthermore, determination of the mechanisms of colistin and
      tigecycline resistance and molecular typing by the tri-locus sequence typing
      (3LST) scheme for nine isolates recovered from bloodstream infections were
      performed. Out of nine isolates, five tigecycline- and two colistin-resistant
      isolates were blaOXA-23 producers of 3LST ST101 corresponding to the
      international clone II recovered during 2012-2013. All nine isolates were
      positive for the presence of the adeB gene of the AdeABC efflux pump. Three
      colistin-resistant isolates possessed novel substitutions in PmrB, which may be
      implicated in colistin resistance. To the best of our knowledge, this is the
      first report of the acquisition of tigecycline and colistin resistance among
      blaOXA-23-producing A. baumannii of 3LST ST101 in Greece; thus, continuous
      surveillance and molecular characterization, prudent use of antibiotics and
      implementation of infection control measures for A. baumannii are urgent.

PMID- 26297502
TI  - Integrated analyses of copy number variations and gene differential expression in
      lung squamous-cell carcinoma.
AB  - BACKGROUND: Although numerous efforts have been made, the pathogenesis underlying
      lung squamous-cell carcinoma (SCC) remains unclear. This study aimed to identify
      the CNV-driven genes by an integrated analysis of both the gene differential
      expression and copy number variation (CNV). RESULTS: A higher burden of the CNVs
      was found in 10-50 kb length. The 16 CNV-driven genes mainly located in chr 1 and
      chr 3 were enriched in immune response [e.g. complement factor H (CFH) and Fc
      fragment of IgG, low affinity IIIa, receptor (FCGR3A)], starch and sucrose
      metabolism [e.g. amylase alpha 2A (AMY2A)]. Furthermore, 38 TFs were screened for
      the 9 CNV-driven genes and then the regulatory network was constructed, in which
      the GATA-binding factor 1, 2, and 3 (GATA1, GATA2, GATA3) jointly regulated the
      expression of TP63. CONCLUSIONS: The above CNV-driven genes might be potential
      contributors to the development of lung SCC.

PMID- 26297503
TI  - Assessment of Foveal Microstructure and Foveal Lucencies Using Optical Coherence
      Tomography Radial Scans Following Macular Hole Surgery.
AB  - PURPOSE: To evaluate the foveal microstructure using high-density (24-line)
      radial scans and their correlation with visual recovery following macular hole
      surgery. DESIGN: Retrospective, consecutive, interventional case series. METHODS:
      Forty-five eyes of 43 patients with >=6 months follow-up following surgery were
      analyzed. Preoperative predictive measures evaluated included basal hole and
      minimum linear diameters. Outcome measures included best-corrected visual acuity
      (BCVA), postoperative foveal lucency horizontal and vertical size, external
      limiting membrane, and ellipsoid zone defect. RESULTS: Mean basal hole diameter
      was 642 +/- 330 MUm and minimum linear diameter was 277 +/- 161 MUm. BCVA
      (logMAR) improved from 0.67 +/- 0.23 to 0.31 +/- 0.16 at 12 months (P < .001).
      Foveal lucency horizontal and vertical sizes (MUm) improved from 97 +/- 81 and 33
      +/- 18 at 1 month to 26 +/- 33 and 19 +/- 18, respectively (P < .05) at 12
      months. External limiting membrane recovered in all cases at 1 month. Mean
      ellipsoid zone defect (MUm) reduced from 136 +/- 164 at 1 month to 32 +/- 33 at
      12 months (P < .05). Preoperative basal hole diameter correlated with horizontal
      foveal lucency size at all time points (P < .05). Horizontal foveal lucency size
      at 1 month correlated (P < .05) with BCVA at 6 and 12 months. Basal hole diameter
      >=700 MUm (71% sensitivity and 70% specificity) and minimum linear diameter >=330
      MUm (71% sensitivity and 70% specificity) were predictive of foveal lucency
      development. Cataract surgery did not influence foveal lucency resolution and no
      holes reopened. CONCLUSION: Using radial scans, 71% of eyes demonstrated a foveal
      lucency at 1 month, whose size correlated with visual recovery. Preoperative
      basal hole diameter was predictive of foveal lucency development and size.

PMID- 26297500
TI  - Reduction in peripheral vascular resistance predicts improvement in insulin
      clearance following weight loss.
AB  - BACKGROUND: The hyperinsulinemia of obesity is a function of both increased
      pancreatic insulin secretion and decreased insulin clearance, and contributes to
      cardiovascular risk. Whilst weight loss is known to enhance insulin clearance,
      there is a paucity of data concerning the underlying mechanisms. This study was
      conducted to examine the inter-relationships between changes in sympathetic
      nervous system (SNS) activity, vascular function and insulin clearance during a
      weight loss program. METHODS: Seventeen non-smoking, un-medicated individuals
      aged 55 +/- 1 years (mean +/- SEM), body mass index (BMI) 33.9 +/- 1.7 kg/m(2),
      underwent a 4-month hypocaloric diet (HCD), using a modified Dietary Approaches
      to Stop Hypertension diet, whilst seventeen age- and BMI-matched subjects acted
      as controls. Insulin sensitivity and insulin clearance were assessed via
      euglycemic hyperinsulinemic clamp (exogenous insulin clearance); hepatic insulin
      extraction was calculated as fasting C-peptide to insulin ratio (endogenous
      insulin clearance); SNS activity was quantified by microneurographic nerve
      recordings of muscle sympathetic nerve activity (MSNA) and whole-body
      norepinephrine kinetics; and vascular function by calf venous occlusion
      plethysmography and finger arterial tonometry. RESULTS: Weight loss averaged -8.3
      +/- 0.6% of body weight in the HCD group and was accompanied by increased clamp
      derived glucose utilization (by 20 +/- 9%, P = 0.04) and exogenous insulin
      clearance (by 12 +/- 5%, P = 0.02). Hepatic insulin extraction increased from 6.3
      +/- 0.8 to 7.1 +/- 0.9 (P = 0.09). Arterial norepinephrine concentration
      decreased by -12 +/- 5%, whole-body norepinephrine spillover rate by -14 +/- 8%,
      and MSNA by -9 +/- 5 bursts per 100 heartbeats in the HCD group (P all >0.05
      versus control group). Step-wise regression analysis revealed a bidirectional
      relationship between enhanced exogenous insulin clearance post weight loss and
      reduction in calf vascular resistance (r = -0.63, P = 0.01) which explained 40%
      of the variance. Increase in hepatic insulin extraction was predicted by enhanced
      finger reactive hyperaemic response (P = 0.006) and improvement in oral glucose
      tolerance (P = 0.002) which together explained 64% of the variance. CONCLUSIONS:
      Insulin clearance is independently and reciprocally associated with changes in
      vascular function during weight loss intervention. Trial registration
      ClinicalTrials.gov: NCT01771042 and NCT00408850.

PMID- 26297504
TI  - Pseudomaricurvus alcaniphilus sp. nov., a marine bacterium isolated from tidal
      flat sediment and emended descriptions of the genus Pseudomaricurvus,
      Pseudomaricurvus alkylphenolicus Iwaki et al. 2014 and Maricurvus nonylphenolicus
      Iwaki et al. 2012.
AB  - A novel Gram-reaction-negative, rod-shaped, aerobic and motile strain, designated
      MEBiC06469T, was isolated from tidal flat sediment of the Taean province, South
      Korea. Strain MEBiC06469T produced ivory-coloured colonies on marine agar 2216
      medium and could degrade carboxymethyl-cellulose. On the basis of 16S rRNA gene
      sequence similarity, the closest relative was Pseudomaricurvus alkylphenolicus
      KU41GT with 96.5 % similarity. The isolate was catalase-positive but oxidase
      negative. Growth was observed at 16-38  degrees C (optimum, 32  degrees C), at pH
      6.0-9.0 (optimum, pH 7.5) and in the presence of 0.0-8.0 % (w/v) NaCl (optimum,
      1.5 %). The only isoprenoid quinone was Q-8.The dominant fatty acids were summed
      feature 3 (comprised of C15 : 0 2-OH and/or C16 : 1omega7c; 20.4 %) and C17 :
      1omega8c (30.9 %), summed feature 8 (comprised of C18 : 1omega7c and/or C18 :
      1omega6c; 9.5 %), C16 : 0 (9.0 %), C15 : 1omega8c (5.3 %), and C11 : 0 3-OH (5.2
      %). Based on these phenotypic properties and phylogenetic data, strain
      MEBiC06469T should be classified as a novel species within the genus
      Pseudomaricurvus for which the name Pseudomaricurvus alcaniphilus sp. nov. is
      proposed. The type strain is MEBiC06469T ( = KCCM 42976T = JCM 18313T). Emended
      descriptions of the genus Pseudomaricurvus, Pseudomaricurvus alkylphenolicusIwaki
      et al. 2014, and Maricurvus nonylphenolicusIwaki et al. 2012 are also provided. 

PMID- 26297505
TI  - Disproportionate Minority Contact.
AB  - The overrepresentation of racial/ethnic minorities within the criminal justice
      system relative to their population percentage, a phenomenon termed
      disproportionate minority contact, has been examined within general adult and
      adolescent offender populations; yet few studies have tested whether this
      phenomenon extends to juvenile sexual offenders (JSOs). In addition, few studies
      have examined whether offender race/ethnicity influences registration and
      notification requirements, which JSOs are subject to in some U.S. states. The
      present study assessed for disproportionate minority contact among general
      delinquent offenders and JSOs, meaning it aimed to test whether the criminal
      justice system treats those accused of sexual and non-sexual offenses differently
      by racial/ethnic group. Furthermore, racial/ethnic group differences in risk,
      legal classification, and sexual offending were examined for JSOs. Results
      indicated disproportionate minority contact was present among juveniles with non
      sexual offenses and JSOs in Alabama. In addition, offense category and risk
      scores differed between African American and European American JSOs. Finally,
      registration classifications were predicted by offending characteristics, but not
      race/ethnicity. Implications and future directions regarding disproportionate
      minority contact among JSOs and social and legal policy affecting JSOs are
      discussed.

PMID- 26297506
TI  - RNA silencing movement in plants.
AB  - Multicellular organisms, like higher plants, need to coordinate their growth and
      development and to cope with environmental cues. To achieve this, various signal
      molecules are transported between neighboring cells and distant organs to control
      the fate of the recipient cells and organs. RNA silencing produces cell non
      autonomous signal molecules that can move over short or long distances leading to
      the sequence specific silencing of a target gene in a well defined area of cells
      or throughout the entire plant, respectively. The nature of these signal
      molecules, the route of silencing spread, and the genes involved in their
      production, movement and reception are discussed in this review. Additionally, a
      short section on features of silencing spread in animal models is presented at
      the end of this review. 

PMID- 26297507
TI  - Birt-Hogg-Dube syndrome: A diagnosis to consider in patients with renal cancer
      and pulmonary cysts.

PMID- 26297508
TI  - Digestive diseases mimicking primary gynecological diseases or with secondary
      gynecological manifestations.
AB  - A wide range of gastrointestinal diseases may spread to and involve genital
      organs by different pathways. These pathways result in extension of the
      pathological process into the extraperitoneal spaces and between the extra- and
      intraperitoneal spaces. These communications occur either via mesenteries and
      ligaments or via the posterior parietal peritoneum. Thus, infectious,
      inflammatory or tumoral digestive diseases can extend into the pelvic organs and
      present with a misleading clinical picture and/or radiological features, showing
      the complexity of pelvic diseases in women. This article reviews, illustrates and
      discusses these different presentations and provides certain clues to help reach
      a definite diagnosis. 

PMID- 26297509
TI  - Ritonavir inhibits intratumoral docetaxel metabolism and enhances docetaxel
      antitumor activity in an immunocompetent mouse breast cancer model.
AB  - Docetaxel (Taxotere((r))) is currently used intravenously as an anticancer agent
      and is primarily metabolized by Cytochrome P450 3A (CYP3A). The HIV protease
      inhibitor ritonavir, a strong CYP3A4 inhibitor, decreased first-pass metabolism
      of orally administered docetaxel. Anticancer effects of ritonavir itself have
      also been described. We here aimed to test whether ritonavir co-administration
      could decrease intratumoral metabolism of intravenously administered docetaxel
      and thus increase the antitumor activity of docetaxel in an orthotopic,
      immunocompetent mouse model for breast cancer. Spontaneously arising
      K14cre;Brca1(F/F) ;p53(F/F) mouse mammary tumors were orthotopically implanted in
      syngeneic mice lacking Cyp3a (Cyp3a(-/-)) to limit ritonavir effects on systemic
      docetaxel clearance. Over 3 weeks, docetaxel (20 mg/kg) was administered
      intravenously once weekly, with or without ritonavir (12.5 mg/kg) administered
      orally for 5 days per week. Untreated mice were used as control for tumor growth.
      Ritonavir treatment alone did not significantly affect the median time of
      survival (14 vs. 10 days). Median time of survival in docetaxel-treated mice was
      54 days. Ritonavir co-treatment significantly increased this to 66 days, and
      substantially reduced relative average tumor size, without altering tumor
      histology. Concentrations of the major docetaxel metabolite M2 in tumor tissue
      were reduced by ritonavir co-administration, whereas tumor RNA expression of
      Cyp3a was unaltered. In this breast cancer model, we observed no direct antitumor
      effect of ritonavir alone, but we found enhanced efficacy of docetaxel treatment
      when combined with ritonavir. Our data, therefore, suggest that decreased
      docetaxel metabolism inside the tumor as a result of Cyp3a inhibition contributes
      to increased antitumor activity.

PMID- 26297510
TI  - Deinococcus metallilatus sp. nov. and Deinococcus carri sp. nov., isolated from a
      car air-conditioning system.
AB  - Two bacterial strains, designated MA1002(T) and MA1003(T), were isolated from the
      air-conditioning system of a car. Cells of both strains were Gram-reaction
      positive, non-motile, non-spore-forming coccoids, catalase- and oxidase-positive
      and UV-radiation resistant. The major fatty acids of strain MA1002(T) were iso
      C17 : 0 and iso-C15 : 0 and those of strain MA1003(T) were iso-C16 : 0 and iso
      C16 : 1 H. The polar lipid profile of MA1002(T) contained
      phosphatidylethanolamine, two unidentified phosphoglycolipids, an unidentified
      phospholipid, an unidentified aminophospholipid, an unidentified aminolipid and
      an unidentified lipid. MA1003(T) had three unidentified phosphoglycolipids, six
      unidentified phospholipids, two unidentified glycolipids and two unidentified
      polar lipids as the polar lipids. The G+C contents of the genomic DNA of
      MA1002(T) and MA1003(T) were 70.5 and 76.0 mol%, respectively. MK-8 was the
      predominant respiratory quinone for both strains. 16S rRNA gene sequence analysis
      showed that strain MA1002(T) was phylogenetically related to Deinococcus
      apachensis DSM 19763(T), D. geothermalis DSM 11300(T), D. aerius TR0125(T) and D.
      aetherius ST0316(T) (92.9, 92.6, 92.0 and 91.9% sequence similarity,
      respectively), and MA1003(T) showed the highest sequence similarity to
      Deinococcus hopiensis KR-140(T) (92.9%) and D. xinjiangensis X-82(T) (91.4%). The
      results of genotypic and phenotypic characterizations showed that both strains
      could be distinguished from phylogenetically related species, and that the
      strains represented novel species within the genus Deinococcus, for which we
      propose the names Deinococcus metallilatus sp. nov. (type strain MA1002(T) = KACC
      17964(T) = NBRC 110141(T)) and Deinococcus carri sp. nov. (type strain is
      MA1003(T) = KACC 17965(T) = NBRC 110142(T)).

PMID- 26297511
TI  - Relation of Total and Cardiovascular Death Rates to Climate System, Temperature,
      Barometric Pressure, and Respiratory Infection.
AB  - A distinct seasonal pattern in total and cardiovascular death rates has been
      reported. The factors contributing to this pattern have not been fully explored.
      Seven locations (average total population 71,354,000) were selected where data
      were available including relatively warm, cold, and moderate temperatures. Over
      the period 2004 to 2009, there were 2,526,123 all-cause deaths, 838,264
      circulatory deaths, 255,273 coronary heart disease deaths, and 135,801 ST
      elevation myocardial infarction (STEMI) deaths. We used time series and
      multivariate regression modeling to explore the association between death rates
      and climatic factors (temperature, dew point, precipitation, barometric
      pressure), influenza levels, air pollution levels, hours of daylight, and day of
      week. Average seasonal patterns for all-cause and cardiovascular deaths were very
      similar across the 7 locations despite differences in climate. After adjusting
      for multiple covariates and potential confounders, there was a 0.49% increase in
      all-cause death rate for every 1 degrees C decrease. In general, all-cause,
      circulatory, coronary heart disease and STEMI death rates increased linearly with
      decreasing temperatures. The temperature effect varied by location, including
      temperature's linear slope, cubic fit, positional shift on the temperature axis,
      and the presence of circulatory death increases in locally hot temperatures. The
      variable effect of temperature by location suggests that people acclimatize to
      local temperature cycles. All-cause and circulatory death rates also demonstrated
      sizable associations with influenza levels, dew point temperature, and barometric
      pressure. A greater understanding of how climate, temperature, and barometric
      pressure influence cardiovascular responses would enhance our understanding of
      circulatory and STEMI deaths. 

PMID- 26297512
TI  - Comparison of Inhospital Outcomes of Surgical Aortic Valve Replacement in
      Hospitals With and Without Availability of a Transcatheter Aortic Valve
      Implantation Program (from a Nationally Representative Database).
AB  - We hypothesized that the availability of a transcatheter aortic valve
      implantation (TAVI) program in hospitals impacts the overall management of
      patients with aortic valve disease and hence may also improve postprocedural
      outcomes of conventional surgical aortic valve replacement (SAVR). The aim of the
      present study was to compare the inhospital outcomes of SAVR in centers with
      versus without availability of a TAVI program in an unrestricted large nationwide
      patient population >50 years of age. SAVRs performed on patients aged >50 years
      were identified from the Nationwide Inpatient Sample (NIS) for the years 2011 and
      2012 using the International Classification of Diseases, Ninth Revision, Clinical
      Modification procedure codes. SAVR cases were divided into 2 categories: those
      performed at hospitals with a TAVI program (SAVR-TAVI) and those without (SAVR
      non-TAVI). A total of 9,674 SAVR procedures were identified: 4,526 (46.79%) in
      the SAVR-TAVI group and 5,148 (53.21%) in SAVR-non-TAVI group. The mean age of
      the study population was 70.2 +/- 0.1 years with majority (53%) of the patients
      aged >70 years. The mean Charlson's co-morbidity score for patients in SAVR-TAVI
      group was greater (greater percentage of patients were aged >80 years, had
      hypertension, congestive heart failure, renal failure, and peripheral arterial
      disease) than that of patients in SAVR-non-TAVI group (1.6 vs 1.4, p <0.001). The
      propensity score matching analysis showed a statistically significant lower
      inhospital mortality (1.25% vs 1.72%, p = 0.001) and complications rate (35.6% vs
      37.3%, p = 0.004) in SAVR-TAVI group compared to SAVR-non-TAVI group. The mean
      length of hospital stay was similar in the 2 groups the cost of hospitalization
      was higher in the SAVR-TAVI group ($43,894 +/- 483 vs $41,032 +/- 473, p
      <0.0001). Having a TAVI program was a significant predictor of reduced mortality
      and complications rate after SAVR in multivariate analysis. In conclusion, this
      largest direct comparative analysis demonstrates that SAVRs performed in centers
      with a TAVI program are associated with significantly lower mortality and
      complications rates compared to those performed in centers without a TAVI
      program. 

PMID- 26297515
TI  - Microbubble Void Imaging: A Non-invasive Technique for Flow Visualisation and
      Quantification of Mixing in Large Vessels Using Plane Wave Ultrasound and
      Controlled Microbubble Contrast Agent Destruction.
AB  - There is increasing recognition of the influence of the flow field on the
      physiology of blood vessels and their development of pathology. Preliminary work
      is reported on a novel non-invasive technique, microbubble void imaging, which is
      based on ultrasound and controlled destruction of microbubble contrast agents,
      permitting flow visualisation and quantification of flow-induced mixing in large
      vessels. The generation of microbubble voids can be controlled both spatially and
      temporally using ultrasound parameters within the safety limits. Three different
      model vessel geometries-straight, planar-curved and helical-with known effects on
      the flow field and mixing were chosen to evaluate the technique. A high-frame
      rate ultrasound system with plane wave transmission was used to acquire the
      contrast-enhanced ultrasound images, and an entropy measure was calculated to
      quantify mixing. The experimental results were cross-compared between the
      different geometries and with computational fluid dynamics. The results indicated
      that the technique is able to quantify the degree of mixing within the different
      configurations, with a helical geometry generating the greatest mixing, and a
      straight geometry, the lowest. There is a high level of concordance between the
      computational fluid dynamics and experimental results. The technique could also
      serve as a flow visualisation tool. 

PMID- 26297514
TI  - Signaling Over Distances.
AB  - Neurons are extremely polarized cells. Axon lengths often exceed the dimension of
      the neuronal cell body by several orders of magnitude. These extreme axonal
      lengths imply that neurons have mastered efficient mechanisms for long distance
      signaling between soma and synaptic terminal. These elaborate mechanisms are
      required for neuronal development and maintenance of the nervous system. Neurons
      can fine-tune long distance signaling through calcium wave propagation and
      bidirectional transport of proteins, vesicles, and mRNAs along microtubules. The
      signal transmission over extreme lengths also ensures that information about axon
      injury is communicated to the soma and allows for repair mechanisms to be
      engaged. This review focuses on the different mechanisms employed by neurons to
      signal over long axonal distances and how signals are interpreted in the soma,
      with an emphasis on proteomic studies. We also discuss how proteomic approaches
      could help further deciphering the signaling mechanisms operating over long
      distance in axons. 

PMID- 26297513
TI  - Investigating the underlying mechanisms of aberrant behaviors in bipolar disorder
      from patients to models: Rodent and human studies.
AB  - Psychiatric patients with bipolar disorder suffer from states of depression and
      mania, during which a variety of symptoms are present. Current treatments are
      limited and neurocognitive deficits in particular often remain untreated.
      Targeted therapies based on the biological mechanisms of bipolar disorder could
      fill this gap and benefit patients and their families. Developing targeted
      therapies would benefit from appropriate animal models which are challenging to
      establish, but remain a vital tool. In this review, we summarize approaches to
      create a valid model relevant to bipolar disorder. We focus on studies that use
      translational tests of multivariate exploratory behavior, sensorimotor gating,
      decision-making under risk, and attentional functioning to discover profiles that
      are consistent between patients and rodent models. Using this battery of
      translational tests, similar behavior profiles in bipolar mania patients and mice
      with reduced dopamine transporter activity have been identified. Future
      investigations should combine other animal models that are biologically relevant
      to the neuropsychiatric disorder with translational behavioral assessment as
      outlined here. This methodology can be utilized to develop novel targeted
      therapies that relieve symptoms for more patients without common side effects
      caused by current treatments. 

PMID- 26297516
TI  - Pre-sedation and transport of Rhamdia quelen in water containing essential oil of
      Lippia alba: metabolic and physiological responses.
AB  - The effects of transporting silver catfish (Rhamdia quelen) for 6 h in plastic
      bags containing 0 (control), 30 or 40 uL/L of essential oil (EO) from Lippia alba
      leaves were investigated. Prior to transport, the fish in the two experimental
      groups were sedated with 200 uL/L of EO for 3 min. After transport, dissolved
      oxygen, carbon dioxide, alkalinity, water hardness, pH, temperature and un
      ionized ammonia levels in the transport water did not differ significantly among
      the groups. However, total ammonia nitrogen levels and net Na(+), Cl(-) and K(+)
      effluxes were significantly lower in the groups transported with EO of L. alba
      than those in the control group. PvO2, PvCO2 and HCO3(-) were higher after
      transporting fish in 40 uL/L of EO of L. alba, but there were no significant
      differences between groups regarding blood pH or hematocrit. Cortisol levels were
      significantly higher in fish transported in 30 uL/L of EO of L. alba compared to
      those of the control group. The metabolic parameters (glycogen, lactate, total
      amino acid, total ammonia and total protein) showed different responses after
      adding EO to the transport water. In conclusion, while the EO of L. alba is
      recommended for fish transport in the conditions tested in the present study
      because it was effective in reducing waterborne total ammonia levels and net ion
      loss, the higher hepatic oxidative stress in this species with the same EO
      concentrations reported by a previous study led us to conclude that the 10-20
      uL/L concentration range of EO and lack of pre-sedation before transport are more
      effective.

PMID- 26297517
TI  - MRI-detected bone marrow changes within 3 weeks after initiation of high-dose
      corticosteroid therapy: a possible change preceding the subsequent appearance of
      low-intensity band in femoral head osteonecrosis.
AB  - Osteonecrosis of the femoral head is considered to occur early during the course
      of corticosteroid treatment. However, it remains unclear exactly how early it can
      develop after initiation of corticosteroid treatment. We report a case of
      osteonecrosis of the femoral head in which abnormal findings were observed on
      short-tau inversion recovery (STIR) sequence image performed 2 weeks and 4 days
      after initiation of high-dose corticosteroid therapy. A 45-year-old man with
      hemophagocytic syndrome was started on prednisolone, with a maximum dose of 40
      mg/day. On day 13 after initiation of this corticosteroid therapy, he transiently
      experienced left hip pain with no apparent cause. STIR sequence image 5 days
      after the onset of pain revealed high-intensity bone marrow lesions at the
      femoral neck of both hips. At 3 months after initiation of corticosteroid
      therapy, T1-weighted magnetic resonance imaging revealed concave-shaped low
      intensity bands, which corresponded to the preceding high-intensity lesions on
      both hips. Because of the subsequent progression to collapse of the left femoral
      head, he underwent prosthetic replacement surgery. The high-intensity lesions on
      STIR sequence image indicate the possibility that osteonecrosis can occur within
      3 weeks after initiation of high-dose corticosteroid therapy.

PMID- 26297518
TI  - Sympathetic blocks for visceral cancer pain management: A systematic review and
      EAPC recommendations.
AB  - The neurolytic blocks of sympathetic pathways, including celiac plexus block
      (CPB) and superior hypogastric plexus block (SHPB) , have been used for years.
      The aim of this review was to assess the evidence to support the performance of
      sympathetic blocks in cancer patients with abdominal visceral pain. Only
      comparison studies were included. All data from the eligible trials were analyzed
      using the GRADE system. Twenty-seven controlled studies were considered. CPB,
      regardless of the technique used, improved analgesia and/or decrease opioid
      consumption, and decreased opioid-induced adverse effects in comparison with a
      conventional analgesic treatment. In one study patients treated with superior
      hypogastric plexus block (SHPB) had a decrease in pain intensity and a less
      morphine consumption, while no statistical differences in adverse effects were
      found. The quality of these studies was generally poor due to several
      limitations, including sample size calculation, allocation concealment, no
      intention to treat analysis. However, at least two CPB studies were of good
      quality. Data regarding the comparison of techniques or other issues were sparse
      and of poor quality, and evidence could not be analysed. On the basis of existing
      evidence, CPB has a strong recommendation in patients with pancreatic cancer
      pain. There is a weak recommendation for SHPB, that should be based on individual
      conditions. Data regarding the choice of the technique are sparse and unfit to
      provide any recommendation. 

PMID- 26297519
TI  - Design and Testing of the Degree of Shoulder Involvement in Sports (DOSIS) Scale.
AB  - BACKGROUND: For athletes affected by shoulder problems, the most important
      expectation is to resume sporting activities. The ability to return to sport is
      related to several parameters, including the type and level of sport played. By
      focusing on these parameters, the Degree of Shoulder Involvement in Sports
      (DOSIS) scale allows for a better assessment of the involvement of the shoulder
      in sports. PURPOSE: To design the DOSIS scale and test its psychometric features.
      STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The DOSIS scale was
      developed as a patient self-administered scale by the Sport Committee of SIGASCOT
      (Societa Italiana del Ginocchio Artroscopia Sport Cartilagine Tecnologie
      Ortopediche) to score sports activity based on 3 parameters: (1) type of sport,
      (2) frequency with which the sport is played, and (3) level at which the sport is
      played. In a subsequent phase, the psychometric features of the DOSIS scale were
      measured in a cohort of 85 patients who were affected by recurrent anterior
      shoulder instability and who underwent an open Bristow-Latarjet procedure or an
      arthroscopic Bankart repair. The content validity, criterion validity, construct
      validity, responsiveness, and test-retest reliability were measured and compared
      with the psychometric features of the Tegner activity scale. RESULTS: Neither the
      DOSIS nor the Tegner activity scale showed floor or ceiling effects, but the
      DOSIS scale had a different distribution of scores, with a tendency toward a
      higher percentage of patients with high scores. The test-retest reliability
      analysis of the DOSIS scale revealed excellent intraobserver reliability
      (intraclass correlation coefficient = 0.96). Regarding the construct validity, 3
      of the 4 hypotheses that we tested were significant. The DOSIS scale showed good
      criterion validity when compared with the Tegner activity scale (rho = 0.3, P =
      .003), and the effect size between the preoperative and postoperative DOSIS scale
      was 1.1. CONCLUSION: The DOSIS scale showed acceptable psychometric features and
      seems to be a valid instrument for shoulder assessment in athletes.

PMID- 26297520
TI  - Successful Total Meniscus Reconstruction Using a Novel Fiber-Reinforced Scaffold:
      A 16- and 32-Week Study in an Ovine Model.
AB  - BACKGROUND: Meniscus injuries in the United States result in an estimated 850,000
      surgical procedures each year. Although meniscectomies are the most commonly
      performed orthopaedic surgery, little advancement has been made in meniscus
      replacement and regeneration, and there is currently no total meniscus
      replacement device approved by the Food and Drug Administration. HYPOTHESIS: A
      novel fiber-reinforced meniscus scaffold can be used as a functional total
      meniscus replacement. STUDY DESIGN: Controlled laboratory study. METHODS: A
      tyrosine-derived, polymer fiber-reinforced collagen sponge meniscus scaffold was
      evaluated mechanically (tensile and compressive testing) and histologically after
      16 and 32 weeks of implantation in an ovine total meniscectomy model (N = 20; 16
      implants plus 4 meniscectomies, divided equally over the 2 time periods). The
      extent of cartilage damage was also measured on tibial plateaus by use of
      toluidine blue surface staining and on femoral condyles by use of Mankin scores
      on histological slides. RESULTS: Scaffolds induced formation of neomeniscus
      tissue that remained intact and functional, with breaking loads approximating 250
      N at both 16 and 32 weeks compared with 552 N for native menisci. Tensile
      stiffness values (99 and 74 N/mm at 16 and 32 weeks, respectively) were also
      comparable with those of the native meniscus (147 N/mm). The compressive modulus
      of the neomeniscus tissue (0.33 MPa at both 16 and 32 weeks) was significantly
      increased compared with unimplanted (time 0) scaffolds (0.15 MPa). There was
      histological evidence of extensive tissue ingrowth and extracellular matrix
      deposition, with immunohistochemical evidence of types I and II collagen. Based
      on significantly decreased surface damage scores as well as Mankin scores, the
      scaffold implants provided greater protection of articular cartilage compared
      with the untreated total meniscectomy. CONCLUSION: This novel fiber-reinforced
      meniscus scaffold can act as a functional meniscus replacement, with mechanical
      properties similar to those of the native meniscus, while protecting the
      articular cartilage of the knee from the extensive damage after a total
      meniscectomy. CLINICAL RELEVANCE: This meniscus replacement scaffold has the
      potential to improve surgical treatment and provide better long-term outcomes for
      those suffering from severe meniscus damage.

PMID- 26297521
TI  - Pseudoparalysis From a Massive Rotator Cuff Tear Is Reliably Reversed With an
      Arthroscopic Rotator Cuff Repair in Patients Without Preoperative Glenohumeral
      Arthritis.
AB  - BACKGROUND: Pseudoparalysis is defined as active forward flexion less than 90
      degrees  with full passive motion. There is controversy about the ideal surgical
      management of a massive rotator cuff tear with pseudoparalysis.
      PURPOSE/HYPOTHESIS: The purpose of this study was to prospectively analyze the
      ability to reverse pseudoparalysis with an arthroscopic rotator cuff repair
      (ARCR). The hypothesis was that in the absence of substantial glenohumeral
      arthritis, preoperative fatty infiltration of grade 3 or higher and an
      acromiohumeral interval (AHI) of less than 7 mm would not prevent reversal of
      pseudoparalysis with an ARCR. STUDY DESIGN: Case series; Level of evidence, 4.
      METHODS: A prospective multicenter study of ARCR performed for preoperative
      pseudoparalysis was conducted. The minimum follow-up was 1 year. The mean patient
      age was 63 years, and pseudoparalysis was present for a mean of 4.2 months
      preoperatively. Preoperative radiographic evaluation included plain film
      evaluation of the AHI and Hamada classification and MRI evaluation of fatty
      degeneration and rotator cuff retraction. Functional outcome was determined by
      the Simple Shoulder Test (SST), American Shoulder and Elbow Surgeons (ASES)
      Shoulder Score, visual analog scale (VAS), and subjective shoulder value (SSV).
      RESULTS: Of the 58 patients enrolled, 56 had at least 1 year of follow-up. Mean
      active forward flexion improved from 47 degrees  preoperatively to 159 degrees 
      postoperatively (P < .001). Statistically significant improvements were seen in
      the SST (from 2.8 preoperatively to 10.1 postoperatively), SSV (from 28 to 83),
      ASES Shoulder Score (from 37 to 88), and VAS (from 5.7 to 1.1) (P < .001).
      Pseudoparalysis was reversed in 53 of 56 patients (95%). There was no difference
      in the rate of reversal of pseudoparalysis between those patients with an AHI of
      less than 7 mm (88.2%) and those with an AHI of 7 mm or more (96.9%) (P =.289).
      Pseudoparalysis was reversed in all 8 of the patients with fatty degeneration of
      grade 3 or higher in 1 or more of the rotator cuff muscles. CONCLUSION: ARCR can
      lead to reversal of preoperative pseudoparalysis in patients with minimal
      preoperative glenohumeral arthritis. ARCR is a viable first line of treatment for
      patients with pseudoparalysis in the absence of advanced glenohumeral arthritis.

PMID- 26297523
TI  - Hand hygiene assessment in the workplace using a UV lamp.
AB  - The aim of this study was to determine the quality of the hand hygiene (HH)
      technique of healthcare workers (HCW) in real conditions, without previous
      education or training. All 705 participants did the World Health Organization
      sequence for HH correctly, but only 9.5% actually achieved the highest rating
      (ie, all hand areas with hand rub distribution). 

PMID- 26297522
TI  - Chronic Degeneration Leads to Poor Healing of Repaired Massive Rotator Cuff Tears
      in Rats.
AB  - BACKGROUND: Chronic rotator cuff tears present a clinical challenge, often with
      poor outcomes after surgical repair. Degenerative changes to the muscle, tendon,
      and bone are thought to hinder healing after surgical repair; additionally, the
      ability to overcome degenerative changes after surgical repair remains unclear.
      PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate healing outcomes of
      muscle, tendon, and bone after tendon repair in a model of chronic rotator cuff
      disease and to compare these outcomes to those of acute rotator cuff injuries and
      repair. The hypothesis was that degenerative rotator cuff changes associated with
      chronic multitendon tears and muscle unloading would lead to poor structural and
      mechanical outcomes after repair compared with acute injuries and repair. STUDY
      DESIGN: Controlled laboratory study. METHODS: Chronic rotator cuff injuries,
      induced via detachment of the supraspinatus (SS) and infraspinatus (IS) tendons
      and injection of botulinum toxin A into the SS and IS muscle bellies, were
      created in the shoulders of rats. After 8 weeks of injury, tendons were
      surgically reattached to the humeral head, and an acute, dual-tendon injury and
      repair was performed on the contralateral side. After 8 weeks of healing, muscles
      were examined histologically, and tendon-to-bone samples were examined
      microscopically, histologically, and biomechanically and via micro-computed
      tomography. RESULTS: All repairs were intact at the time of dissection, with no
      evidence of gapping or ruptures. Tendon-to-bone healing after repair in our
      chronic injury model led to reduced bone quality and morphological
      disorganization at the repair site compared with acute injuries and repair. SS
      and IS muscles were atrophic at 8 weeks after repair of chronic injuries,
      indicating incomplete recovery after repair, whereas SS and IS muscles exhibited
      less atrophy and degeneration in the acute injury group at 8 weeks after repair.
      After chronic injuries and repair, humeral heads had decreased total mineral
      density and an altered trabecular structure, and the repair had decreased
      strength, stiffness, and toughness, compared with the acute injury and repair
      group. CONCLUSION: Chronic degenerative changes in rotator cuff muscles, tendons,
      and bone led to inferior healing characteristics after repair compared with acute
      injuries and repair. The changes were not reversible after repair in the time
      course studied, consistent with clinical impressions. CLINICAL RELEVANCE: High
      retear rates after rotator cuff repair are associated with tear size and
      chronicity. Understanding the mechanisms behind this association may allow for
      targeted tissue therapy for tissue degeneration that occurs in the setting of
      chronic tears.

PMID- 26297524
TI  - Epidemiology of CTX-M-type extended-spectrum beta-lactamase-producing Escherichia
      coli among older adults.
AB  - To identify independent predictors for isolation of CTX-M-type extended-spectrum
      beta-lactamase-producing Escherichia coli (CTX-M E coli) in older adults (>65
      years old), 87 cases with CTX-M E coli isolation were compared with matched
      controls without E coli isolation. Institutionalized residence, multiple
      comorbidities, and urinary catheter were independent predictors of CTX-M E coli
      among older adults. 

PMID- 26297525
TI  - Effect of daily chlorhexidine bathing on acquisition of carbapenem-resistant
      Acinetobacter baumannii (CRAB) in the medical intensive care unit with CRAB
      endemicity.
AB  - BACKGROUND: There is insufficient evidence for daily chlorhexidine bathing to
      reduce nosocomial spread of carbapenem-resistant Acinetobacter baumannii (CRAB)
      in endemic situations. METHODS: An interrupted time series study was performed to
      evaluate the effect of daily chlorhexidine bathing on the acquisition of CRAB in
      a medical intensive care unit (ICU) with CRAB endemicity. There was a 14-month
      control period and 12-month chlorhexidine bathing period. Segmented Poisson
      regression analysis was performed to assess the impact of chlorhexidine bathing
      on the level and trend of the series of prevalence rates and incidence density.
      Also, chlorhexidine susceptibility testing was performed on CRAB isolates
      collected during the chlorhexidine bathing period. RESULTS: There was a 51.8%
      reduction of CRAB acquisition rates after an introduction of daily chlorhexidine
      bathing (44.0 vs 21.2 cases/1,000 at-risk patient days, P < .001). There was a
      significant reduction in the level (-0.604; 95% CI, -0.904 to -0.305; P < .001)
      of incidence density of CRAB, whereas there was no significant change in both
      level and trend of CRAB prevalence rates. Minimum inhibitory concentration of
      chlorhexidine against a total of 98 CRAB isolates ranged from 8-64 MUg/mL.
      CONCLUSION: Daily chlorhexidine bathing significantly reduces the acquisition of
      CRAB in a medical ICU with CRAB endemicity.

PMID- 26297526
TI  - Depressive Symptoms, Family Functioning and Quality of Life in Chinese Patients
      with Type 2 Diabetes.
AB  - OBJECTIVE: Patients with type 2 diabetes mellitus often have depression or
      depressive symptoms, impaired family functioning and poor quality of life. This
      study aimed to examine relationships among psychological variables, including
      depressive symptoms, family functioning and quality of life, for Chinese patients
      with type 2 diabetes and to explore the influencing factors on quality of life
      for these patients. METHOD: In this cross-sectional study, 257 patients with type
      2 diabetes and 259 nondiabetic community controls completed the Beck Depression
      Inventory, the Family Assessment Device, and the Quality of Life Enjoyment and
      Satisfaction Questionnaire-Short Form. RESULTS: Patients with type 2 diabetes
      reported significant family impairment in the dimension of affective involvement
      compared with nondiabetic community controls (p<0.05). Mean Family Assessment
      Device scores were negatively associated with quality of life scores among
      patients with type 2 diabetes. Age, depressive symptoms, duration of diabetes,
      communication, affective involvement and behavioural control were associated with
      quality of life in patients with type 2 diabetes. CONCLUSIONS: The results
      indicate that having type 2 diabetes was associated with some difficulties with
      family functioning and that poor family functioning was associated with a poorer
      quality of life. Additional factors, including older age, depressive symptoms,
      duration of diabetes, and some dimensions of family functioning, were found to be
      associated with quality of life in Chinese individuals with type 2 diabetes.

PMID- 26297527
TI  - Effect of postprandial hyperglycaemia on coronary flow reserve in patients with
      impaired glucose tolerance and type 2 diabetes mellitus.
AB  - BACKGROUND: This study investigated whether postprandial hyperglycaemia has an
      adverse effect on coronary microvascular function and left ventricular diastolic
      function. METHODS: In all, 28 patients with type 2 diabetes mellitus with no
      significant stenosis in left anterior descending artery were enrolled. In all
      subjects, plasma 1,5-anhydroglucitol was measured, and coronary flow reserve in
      the left anterior descending artery was evaluated using a Doppler wire. Membrane
      type-1 matrix metalloproteinase expression on circulating peripheral blood
      mononuclear cells was measured by flow cytometry. Correlation analyses were
      performed for coronary flow reserve and 1,5-anhydroglucitol, other coronary risk
      factors, membrane type-1 matrix metalloproteinase and E/e'. RESULTS: Strong
      correlations were found only between 1,5-anhydroglucitol and coronary flow
      reserve and membrane type-1 matrix metalloproteinase. On multiple regression
      analysis, 1,5-anhydroglucitol remained an independent predictor of coronary flow
      reserve (beta = 0.38, p = 0.048). CONCLUSION: Postprandial hyperglycaemia appears
      to have an adverse effect on coronary microvascular function, suggesting that
      improvement of postprandial hyperglycaemia may contribute to the improvement of
      coronary microvascular dysfunction.

PMID- 26297528
TI  - Prior treatment with dipeptidyl peptidase 4 inhibitors is associated with better
      functional outcome and lower in-hospital mortality in patients with type 2
      diabetes mellitus admitted with acute ischaemic stroke.
AB  - It is unclear whether prior antidiabetic treatment affects stroke severity and
      outcome. To evaluate this association, we prospectively studied all patients who
      were admitted in our Department with acute ischaemic stroke (n = 378, mean age =
      78.8 +/- 6.5 years). The severity of stroke was assessed at admission with the
      National Institutes of Health Stroke Scale. The outcome was assessed with the
      modified Rankin Scale at discharge and with in-hospital mortality. A total of 123
      patients had type 2 diabetes mellitus. At admission, there was a trend for lower
      National Institutes of Health Stroke Scale in patients treated with dipeptidyl
      peptidase 4 inhibitors compared with patients treated with other antidiabetic
      agents (6.1 +/- 7.5 vs 10.0 +/- 9.2, respectively; p = 0.079). At discharge,
      patients treated with dipeptidyl peptidase 4 inhibitors had lower modified Rankin
      Scale than patients treated with other antidiabetic agents (2.1 +/- 1.9 vs 3.2 +/
      2.1, respectively; p < 0.05). Patients treated with dipeptidyl peptidase 4
      inhibitors also had lower in-hospital mortality than patients treated with other
      antidiabetic agents (0.0% vs 15.1%, respectively; p < 0.05). In conclusion, prior
      treatment with dipeptidyl peptidase 4 inhibitors in patients with acute ischaemic
      stroke appears to be associated with better functional outcome and lower
      mortality risk. 

PMID- 26297529
TI  - Reactivation of hepatitis B virus during interferon-free therapy with daclatasvir
      and asunaprevir in patient with hepatitis B virus/hepatitis C virus co-infection.
AB  - Direct-acting antiviral agents (DAA) for hepatitis C virus (HCV) are not
      effective for hepatitis B virus (HBV), which may be suggestive of reactivation of
      anti-HBe hepatitis during interferon (IFN)-free DAA therapy in HBV/HCV co
      infected patients with inactive HBV. A 69-year-old male patient was diagnosed
      with chronic hepatitis due to HBV/HCV co-infection with serum levels of alanine
      aminotransferase (ALT) of 94 U/L, HCV RNA of 4.2 log IU/mL and HBV DNA of 2.5 log
      copies/mL. HCV was thought to be responsible for the hepatitis activity because
      of low level of HBV core-related antigen (3.1 log U/mL). He was treated with
      combination therapy of daclatasvir and asunaprevir. Serum ALT gradually
      increased, and reached 237 U/L on day 43 in spite of undetectable HCV RNA. Serum
      HBV DNA was increasing to 7.0 log copies/mL at that time. The treatment was
      stopped due to suspicion of drug-induced liver injury and/or HBV reactivation.
      Administration of entecavir reduced HBV DNA levels, followed by improvement in
      ALT levels. This report proposes that close monitoring of HBV DNA during the anti
      HCV DAA therapy and the commencement of anti-HBV therapy with nucleoside analogs
      after the increase of HBV DNA should be considered in patients with HBV/HCV co
      infection. 

PMID- 26297530
TI  - A novel bioactive membrane by cell electrospinning.
AB  - Electrospinning permits fabrication of biodegradable matrices that can resemble
      the both scale and mechanical behavior of the native extracellular matrix.
      However, achieving high-cellular density and infiltration of cells within
      matrices with traditional technique remain challenging and time consuming. The
      cell electrospinning technique presented in this paper can mitigate the problems
      associated with these limitations. Cells encapsulated by the material in the cell
      electrospinning technique survived well and distributed homogenously within the
      nanofibrous membrane, and their vitality was improved to 133% after being
      cultured for 28 days. The electrospun nanofibrous membrane has a certain
      degradation property and favorable cell-membrane interaction that supports the
      active biocompatibility of the membrane. Its properties are helpful for
      supporting cell attachment and growth, maintaining phenotypic shape, and
      secreting an ample amount of extracellular matrix (ECM). This novel membrane may
      be a potential application within the field of tissue engineering. The ability of
      cell electrospinning to microintegrate cells into a biodegradable fibrous matrix
      embodies a novel tissue engineering approach that could be applied to fabricate a
      high cell density elastic tissue mimetic.

PMID- 26297531
TI  - Effects of Ginko biloba leaf extract on the neurogenesis of the hippocampal
      dentate gyrus in the elderly mice.
AB  - Aging is associated with reduced hippocampal neurogenesis, which may in turn
      contribute to cognitive impairment. We assessed the effect of Ginkgo biloba (Gb)
      on hippocampal neurogenesis in elderly male mice using immunohistochemistry. We
      used anti-caspase-3 as a marker of apoptosis, anti-GFAP as a marker of neural
      stem cells, anti-Ki-67 as a specific marker for cellular proliferation and anti
      doublecortin (DCX) to detect newly born neurons in the hippocampal dentate gyrus
      (DG) of aged male mice. The 24-month-old male mice were divided into two groups:
      a control group treated with distilled water and a group fed with Gb at a dose of
      100 mg/kg once daily for 28 days. A sharp decrease in apoptotic cells in Gb
      treated compared to nontreated mice was observed by anti-csapase-3
      immunostaining. A large number of GFAP+ve cells was found in the subgranular zone
      of the DG of Gb-treated mice, suggesting an increase in the pool of neural stem
      cells by Gb treatment. There was also an increase in Ki-67 immunoreactive cells,
      indicating increased cell proliferation in the DG in the Gb-treated compared to
      nontreated group. A significant increase in newborn DCX+ve neurons with well
      developed tertiary dendrites was also found in the Gb-treated compared to
      nontreated group. Using Western blot analysis, the expression of DCX protein in
      the Gb group was also significantly increased compared to the control. The
      results support a beneficial role of Gb on hippocampal neurogenesis in the
      context of brain aging. 

PMID- 26297532
TI  - Editor's spotlight/take 5: sex-specific analysis of data in high-impact
      orthopaedic journals: how are we doing?

PMID- 26297534
TI  - Tomorrow's vector vaccines for small ruminants.
AB  - Inactivated and attenuated vaccines have contributed to the control or even the
      eradication of significant animal pathogens. However, these traditional vaccine
      technologies have limitations and disadvantages. Inactivated vaccines lack
      efficacy against certain pathogens, while attenuated vaccines are not always as
      safe. New technology vaccines, namely DNA and recombinant viral vector vaccines,
      are being developed and tested against pathogens of small ruminants. These
      vaccines induce both humoral and cellular immune responses, are safe to
      manufacture and use and can be utilized in strategies for differentiation of
      infected from vaccinated animals. Although there are more strict regulatory
      requirements for the safety standards of these vaccines, once a vaccine platform
      is evaluated and established, effective vaccines can be rapidly produced and
      deployed in the field to prevent spread of emerging pathogens. The present
      article offers an introduction to these next generation technologies and examples
      of vaccines that have been tested against important diseases of sheep and goats. 

PMID- 26297533
TI  - Optimizing Treatment of Elderly COPD Patients: What Role for Inhaled
      Corticosteroids?
AB  - The most recent international documents on the management and therapy of chronic
      obstructive pulmonary disease (COPD) recommend inhaled corticosteroids (ICS) in
      addition to long-acting bronchodilators as maintenance treatment for patients at
      high risk of exacerbations, namely patients with forced expiratory volume in 1 s
      (FEV1) of <50% predicted and/or more than one exacerbation per year. However, ICS
      are widely used in up to 70% of COPD patients, including those at low risk of
      exacerbations. In recent years, concerns about the potential adverse effects of
      this drug category have been raised, and both observational and clinical studies
      have shown that elderly subjects with COPD treated with ICS are at high risk of
      developing cataracts and diabetes and more severe and life-threatening conditions
      such as pneumonia and osteoporotic fractures. Moreover, aging is characterized by
      memory impairment, decline in muscle strength and body mass impaired
      coordination, as well as alterations in eyesight and hearing that can impede
      proper use of devices currently available for ICS administration. Thus, regular
      use of ICS in more elderly patients with COPD should follow guideline
      recommendations, be considered with caution, and be based upon carefully weighing
      up expected benefits with the risk of undesired, adverse effects.

PMID- 26297535
TI  - Activation of mTOR dependent signaling pathway is a necessary mechanism of
      antidepressant-like activity of zinc.
AB  - The rapid antidepressant response to the N-methyl-D-aspartate (NMDA) receptor
      antagonists is mediated by activation of the mammalian target of the rapamycin
      (mTOR) signaling pathway, an increase in the synthesis of synaptic proteins and
      formation of new synapses in the prefrontal cortex (PFC) of rats. Zinc (Zn),
      which is a potent NMDA receptor antagonist, exerts antidepressant-like effects in
      screening tests and models of depression. We focused these studies in
      investigating whether activation of the mTOR signaling pathway is also a
      necessary mechanism of the antidepressant-like activity of Zn. We observed that a
      single injection of Zn (5 mg/kg) induced an increase in the phosphorylation of
      mTOR and p70S6K 30 min and 3 h after Zn treatment at time points when Zn produced
      also an antidepressant-like effect in the forced swim test (FST). Furthermore, Zn
      administered 3 h before the decapitation increased the level of brain derived
      neurotrophic factor (BDNF), GluA1 and synapsin I. An elevated level of GluA1 and
      synapsin I was still observed 24 h after the Zn treatment, although Zn did not
      produce any effects in the FST at that time point. We also observed that
      pretreatment with rapamycin (mTORC1 inhibitor), LY294002 (PI3K inhibitor), H-89
      (PKA inhibitor) and GF109203X (PKC inhibitor) blocked the antidepressant-like
      effect of Zn in FST in rats and blocks Zn-induced activation of mTOR signaling
      proteins (analyzed 30 min after Zn administration). These studies indicated that
      the antidepressant-like activity of Zn depends on the activation of mTOR
      signaling and other signaling pathways related to neuroplasticity, which can
      indirectly modulate mTOR function.

PMID- 26297536
TI  - Identification of histaminergic neurons through histamine 3 receptor-mediated
      autoinhibition.
AB  - Using a reporter mouse model with expression of the tomato fluorescent protein
      under the dopamine transporter promoter (Tmt-DAT) we discovered a new group of
      neurons in the histaminergic tuberomamillary nucleus (TMN), which, in contrast to
      tuberoinfundibular dopaminergic neurons of the dorsomedial arcuate nucleus, do
      not express tyrosine hydroxylase but can synthesize and store dopamine. Tmt-DAT
      neurons located within TMN share electrophysiological properties with
      histaminergic neurons: spontaneous firing at a membrane potential around -50 mV
      and presence of hyperpolarization-activated cyclic nucleotide-gated ion channels.
      Histamine (30 MUM) depolarizes and excites Tmt-DAT neurons through H1R activation
      but inhibits histaminergic neurons through H3R activation thus allowing a
      pharmacological identification of the different neurons. Single-cell RT-PCR
      revealed that all histaminergic neurons expressing histidine decarboxylase (HDC)
      also express H3R. This includes neurons retrogradely traced from the striatum
      whose inhibition by a selective H3R agonist was indistinguishable from the whole
      population. Prolonged depolarization reduces the autoinhibition. The potency of
      histamine at H3R depends on membrane potential and on extracellular and
      intracellular calcium. Autoinhibition can be impaired by preincubation with
      capsaicin, a ligand of the calcium-permeable TRPV1 channel or by blockade of
      Ca(2+)-ATPase with thapsigargin. The pharmacology of autoinhibition is revisited
      and physiological conditions for its functionality are determined. Usage of
      reporter mouse models for the safe identification of aminergic neurons under
      pathophysiological conditions is recommended. This article is part of the Special
      Issue entitled 'Histamine Receptors'.

PMID- 26297537
TI  - RGS proteins destroy spare receptors: Effects of GPCR-interacting proteins and
      signal deamplification on measurements of GPCR agonist potency.
AB  - Many GPCRs are able to activate multiple distinct signaling pathways, and these
      may include biochemical cascades activated via either heterotrimeric G proteins
      or by beta-arrestins. The relative potencies and/or efficacies among a series of
      agonists that act on a common receptor can vary depending upon which signaling
      pathway is being activated. This phenomenon is known as biased signaling or
      functional selectivity, and is presumed to reflect underlying differences in
      ligand binding affinities for alternate conformational states of the receptor.
      The first part of this review discusses how various cellular GPCR interacting
      proteins (GIPs) can influence receptor conformation and thereby affect ligand
      receptor interactions and contribute to signaling bias. Upon activation,
      receptors trigger biochemical cascades that lead to altered cellular function,
      and measuring points along the cascade (e.g., second messenger production)
      conveys information about receptor activity. As a signal continues along its way,
      the observed concentration dependence of a GPCR ligand may change due to
      amplification and saturation of biochemical steps. The second part of this review
      considers additional cellular factors that affect signal processing, focusing
      mainly on structural elements and deamplification mechanisms, and discusses the
      relevance of these to measurements of potency and functional selectivity. 

PMID- 26297538
TI  - The temporal increase in HIV-1 non-R5 tropism frequency among newly diagnosed
      patients from northern Poland is associated with clustered transmissions.
AB  - INTRODUCTION: CCR5 (R5) tropic viruses are associated with early stages of
      infection, whereas CXCR4 (X4) HIV-1 tropism has been associated with severe
      immunodeficiency. We investigated the temporal changes in the genotype-predicted
      tropism frequency and the phylogenetic relationships between the R5 and non-R5
      clades. METHODS: A cohort of 194 patients with a newly diagnosed HIV infection
      that was linked to their care from 2007 to 2014 was analyzed. Baseline plasma
      samples were used to assess the HIV-1 genotypic tropism with triplicate V3-loop
      sequencing. The non-R5 tropism prediction thresholds were assigned using a false
      positive rate (FPR) of 10 and 5.75% and associated with clinical and laboratory
      data. The transmission clusters were analyzed using pol sequences with a maximum
      likelihood and Bayesian inference. RESULTS: The overall non-R5 tropism frequency
      for 5.75% FPR was 15.5% (n=30) and 27.8% (n=54) for 10% FPR. The frequency of the
      non-R5 tropism that was predicted using 5.75% FPR increased significantly from
      2007 (0%) to 2014 (n=5/17, 29.4%) (p=0.004, rough slope +3.73%/year) and from 0%
      (2007) to 35.3% (2014, n=6/17) (p=0.071, rough slope +2.9%/year) using 10% FPR.
      Increase in the asymptomatic diagnoses over time was noted (p=0.05, rough slope
      +3.53%/year) along with a tendency to increase the lymphocyte CD4 nadir
      (p=0.069). Thirty-two clusters were identified, and non-R5 tropic viruses were
      found for 26 (30.95%) sequences contained within 14 (43.8%) clusters. Non-R5
      tropism was associated with subtype D variants (p=0.0001) and the presence of
      CCR5 Delta32/wt genotype (p=0.052). CONCLUSIONS: R5 tropism predominates among
      the treatment of naive individuals, but the increases in the frequency of non-R5
      tropic variants may limit the clinical efficacy of the co-receptor inhibitors.
      The rising prevalence of non-R5 HIV-1 may indicate transmission of X4 clades.

PMID- 26297539
TI  - Allowing for population stratification in case-only studies of gene-environment
      interaction, using genomic control.
AB  - Gene-environment interactions (G * E) have attracted considerable research
      interest in the past owing to their scientific and public health implications,
      but powerful statistical methods are required to successfully track down G * E,
      particularly at a genome-wide level. Previously, a case-only (CO) design has been
      proposed as a means to identify G * E with greater efficiency than traditional
      case-control or cohort studies. However, as with genotype-phenotype association
      studies themselves, hidden population stratification (PS) can impact the validity
      of G * E studies using a CO design. Since this problem has been subject to little
      research to date, we used comprehensive simulation to systematically assess the
      type I error rate, power and effect size bias of CO studies of G * E in the
      presence of PS. Three types of PS were considered, namely genetic-only (PSG),
      environment-only (PSE), and joint genetic and environmental stratification
      (PSGE). Our results reveal that the type I error rate of an unadjusted Wald test,
      appropriate for the CO design, would be close to its nominal level (0.05 in our
      study) as long as PS involves only one interaction partner (i.e., either PSG or
      PSE). In contrast, if the study population is stratified with respect to both G
      and E (i.e., if there is PSGE), then the type I error rate is seriously inflated
      and estimates of the underlying G * E interaction are biased. Comparison of CO to
      a family-based case-parents design confirmed that the latter is more robust
      against PSGE, as expected. However, case-parent trios may be particularly
      unsuitable for G * E studies in view of the fact that they require genotype data
      from parents and that many diseases with an environmental component are likely to
      be of late onset. An alternative approach to adjusting for PS is principal
      component analysis (PCA), which has been widely used for this very purpose in
      past genome-wide association studies (GWAS). However, resolving genetic PS
      properly by PCA requires genetic data at the population level, the availability
      of which would conflict with the basic idea of the CO design. Therefore, we
      explored three modified Wald test statistics, inspired by the genomic control
      (GC) approach to GWAS, as an alternative means to allow for PSGE. The modified
      statistics were benchmarked against a stratified Wald test assuming known
      population affiliation, which should provide maximum power under PS. Our results
      confirm that GC is capable of successfully and efficiently correcting the PS
      induced inflation of the type I error rate in CO studies of G * E.

PMID- 26297540
TI  - Rubbery egg challenge.

PMID- 26297541
TI  - Solution to highest melting point challenge.

PMID- 26297542
TI  - miR-125a-5p inhibits cell proliferation and induces apoptosis in colon cancer via
      targeting BCL2, BCL2L12 and MCL1.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that function as regulators of gene
      expression. MiR-125 is a family of miRNAs that have been shown to be involved in
      various cancer types. In this study, for the first time, we showed that miR-125a
      5p was specifically down-regulated in both colon cancer tissue and colon cancer
      cell lines. The tumor suppressor role of miR-125a-5p in colon cancer was
      supported by the observation that overexpression of miR-125a-5p inhibited cell
      proliferation and induced cell apoptosis in colon cancer cells. We also confirmed
      that in colon cancer cells, anti-apoptotic genes BCL2, BCL2L12 and Mcl-1 were
      direct targets of miR-125a-5p, and they were down-regulated by miR-125a-5p
      overexpression. Furthermore, restoration of BCL2, BCL2L12 and Mcl-1 expression in
      colon cancer cells could partially reverse the cell proliferation inhibition and
      apoptosis stimulation caused by miR-125a-5p overexpression, indicating that miR
      125a-5p inhibits cell proliferation and induces apoptosis in colon cancer cells
      via targeting BCL2, BCL2L12 and Mcl-1. 

PMID- 26297543
TI  - Profiling of miRNA expression in immune thrombocytopenia patients before and
      after Qishunbaolier (QSBLE) treatment.
AB  - Immune thrombocytopenia (ITP), also known as idiopathic thrombocytopenic purpura,
      is an autoimmune disease characterized by low platelet count and increased
      bleeding tendency. Currently, glucocorticoid and splenectomy are the main
      therapies for ITP but with obvious side effects including tendency of relapse and
      risk of internal bleeding. In this study, we report the Mongolian medicine
      Qishunbaolier (QSBLE) can significantly and efficiently increase platelet count
      with a low recurrent rate and unnoticeable side effect. We profiled the microRNA
      (miRNA) expression in the blood sample of ITP patients and identified 44 miRNAs
      that are differentially expressed in ITP patients before and after QSBLE
      treatment. Out of these 44 miRNAs, 25 are expressed in control subjects and are
      downregulated in ITP patients, whereas the treatment with QSBLE restores their
      expressions to the level of control subjects. This result suggests that abnormal
      expression of these 25 miRNAs might be connected to the pathogenesis of ITP.
      Interestingly, 14 of those 44 miNRAs are predicted to target at least once on 31
      known IPT associated genes, indicating the possible mechanism of QSBLE on ITP
      therapy. 

PMID- 26297544
TI  - MiR-548-3p functions as an anti-oncogenic regulator in breast cancer.
AB  - Emerging evidence has found that microRNAs (miRNA) play an important role in
      breast cancer. MiR-548 family has been demonstrated to be involved in the
      pathogenesis of several cancers. However, its role in breast cancer has not yet
      been elucidated. To explore this concern, we explored the expression of miR-548
      3p in clinical specimens and breast cancer cells by qRT-PCR. In addition, an CCK
      8 assay and Caspase 3/7 activity were used to evaluated the rates of cell
      proliferation and apoptosis. Protein expression was analyzed by western blotting
      and the target gene was confirmed using a luciferase reporter assay. Our results
      illustrated that miR-548-3p was significantly downregulated in breast cancer.
      Overexpression of miR-548-3p inhibited the proliferation and promoted the
      apoptosis of breast cancer cells. In addition, ECHS1 expression was demonstrated
      to be significantly upregulated in breast cancer tissues and cells, and the ECHS1
      gene was identified to be one target of miR-548-3p. Therefore, our results
      demonstrated that miR-548-3p inhibited the proliferation of breast cancer cells
      by regulating the expression of ECHS1, indicating its potential as a therapeutic
      target for breast cancer. 

PMID- 26297545
TI  - miR-99b suppresses IGF-1R expression and contributes to inhibition of cell
      proliferation in human epidermal keratinocytes.
AB  - Condyloma acuminatum (CA) is a condition caused by the highly contagious human
      papillomavirus (HPV), characterized by warts that undergo abnormal cell
      proliferation. One of the important regulators of cell proliferation is microRNAs
      (miRNAs). In this study, we aimed to investigate the expression profile of miR
      99b in HPV positive CA samples and normal skin. We found significantly lower miR
      99b levels in CA samples than in normal skin. Therefore, we investigated the role
      of miR-99b in regulating the proliferation of primary cultured human epidermal
      keratinocytes, and found that forced expression of miR-99b inhibited
      proliferation and induced G1-phase arrest. Based on conserved sequences in 3'UTR
      for miR-99b binding, we identified the insulin-like growth factor-1 receptor (IGF
      1R) gene as a direct target for miR-99b. Further, we confirmed the binding site
      for miR-99b in the IGF-1R 3'UTR by mutation using a luciferase reporter assay
      that showed decrease in luciferase activity in the presence of miR-99b in the
      construct with the wild-type 3'UTR, but not in the construct with the mutant
      3'UTR. Moreover, miR-99b over-expression could down-regulate IGF-1R expression,
      and could repress the PI3K-AKT signaling pathway. Lastly, over-expression of IGF
      1R reversed the inhibitory effect of miR-99b on keratinocyte proliferation. Taken
      together, our results suggest that IGF-1R levels may be modulated by miR-99b in
      CA: downregulation of miR-99b with concomitant upregulation of its target gene
      IGF-1R may over-induce the PI3K-AKT signaling pathway, leading to deregulated
      cell proliferation in CA. 

PMID- 26297546
TI  - Upregulation of miR-556-5p promoted prostate cancer cell proliferation by
      suppressing PPP2R2A expression.
AB  - The prognosis and survival rate of prostate cancer are very poor. Previous
      studies have shown that miR-556-5p have emerged as important regulators in cancer
      cell biological processes. The role of miR-556-5p in prostate cancer remains
      unclear. In this study, expression of miR-556-5p in prostate cancer cell lines
      and tissues was upregulated. Result of MTT assays, colony formation and anchorage
      independent growth assays demonstrated that overexpression of miR-556-5p promoted
      prostate cancer cell growth. Additionally, PPP2R2A was identified as a direct
      target of miR-556-5p. Ectopic expression of miR-556-5p led to downregulation of
      PPP2R2A protein, which resulted in the downregulation of p27, upregulation of
      cyclin D1. Taken together, our data provide compelling evidence that miR-556-5p
      functions as an onco-miRNA and participates in prostate cancer carcinogenesis by
      suppressing PPP2R2A expression. 

PMID- 26297547
TI  - miR-140-5p inhibits ovarian cancer growth partially by repression of PDGFRA.
AB  - Dysregulation of miRNAs is a common feature in human cancers, and miR-140-5p has
      been found to be down-regulated in cancer. However its role in ovarian cancer
      remains unclear. miR-140-5p was underexpressed in HCC tissues and cell lines
      compared with their normal controls. Additionally, PDGFRA was predicted the
      target gene of miR-140-5p. PDGFRA was inversely correlated with the expression of
      miR-140-5p in ovarian cancer cells. Importantly, we demonstrate that the over
      expression of miR-140-5p significantly inhibits ovarian cancer cell proliferation
      and induces apoptosis. Our results suggest the existence of a novel miR-140-5p
      PDGFRA pathway and indicate that miR-140-5p acts as a tumor suppressor during
      ovarian carcinogenesis. These results may provide a promising alterative strategy
      for the therapeutic treatment of ovarian cancer. 

PMID- 26297548
TI  - MiR-454 inhibited cell proliferation of human glioblastoma cells by suppressing
      PDK1 expression.
AB  - It has been well documented that aberrant expression of microRNAs is associated
      with carcinogenesis of glioblastoma (GBM), however the underlying mechanisms are
      not clear. In this present study, we aimed to clarify the biological function of
      miR-454 in GBM. MiR-454 was identified to be significantly down-regulated in GBM
      primary tumors and cell lines. Overexpression of miR-454 in GBM cells resulted in
      arresting cells at G0/G1 phase and thus inhibiting cell proliferation.
      Bioinformatic analysis predicted 3-phosphoinositide-dependent protein kinase-1
      (PDK1) as a target of miR-454 which acted as a tumor promoter gene. Increased miR
      454 significantly repressed PDK1 expression, and then regulating cell
      proliferation and cell cycle regulators, down-regulation of Cyclin D1 and p-pRb
      and p21 was up-regulated. Taken together, our study has revealed miR-454 as a
      tumor suppressor in GBM. 

PMID- 26297549
TI  - Bioactive peptides derived from natural proteins with respect to diversity of
      their receptors and physiological effects.
AB  - We have found various bioactive peptides derived from animal and plant proteins,
      which interact with receptors for endogenous bioactive peptides such as opioids,
      neurotensin, complements C3a and C5a, oxytocin, and formyl peptides etc. Among
      them, rubiscolin, a delta opioid peptide derived from plant RuBisCO, showed
      memory-consolidating, anxiolytic-like, and food intake-modulating effects.
      Soymorphin, a MU opioid peptide derived from beta-conglycinin showed anxiolytic
      like, anorexigenic, hypoglycemic, and hypotriglyceridemic effects. beta
      Lactotensin derived from beta-lactoglobulin, the first natural ligand for the
      NTS2 receptor, showed memory-consolidating, anxiolytic-like, and
      hypocholesterolemic effects. Weak agonist peptides for the complements C3a and
      C5a receptors were released from many proteins and exerted various central
      effects. Peptides showing anxiolytic-like antihypertensive and anti-alopecia
      effects via different types of receptors such as OT, FPR and AT2 were also
      obtained. Based on these study, new functions and post-receptor mechanisms of
      receptor commom to endogenous and exogenous bioactive peptides have been
      clarified. 

PMID- 26297550
TI  - Do English NHS Microbiology laboratories offer adequate services for the
      diagnosis of UTI in children? Healthcare Quality Improvement Partnership (HQIP)
      Audit of Standard Operational Procedures.
AB  - The National Institute of Care Excellence (NICE) 2007 guidance CG54, on urinary
      tract infection (UTI) in children, states that clinicians should use urgent
      microscopy and culture as the preferred method for diagnosing UTI in the hospital
      setting for severe illness in children under 3 years old and from the GP setting
      in children under 3 years old with intermediate risk of severe illness. NICE also
      recommends that all 'infants and children with atypical UTI (including non
      Escherichia coli infections) should have renal imaging after a first infection'.
      We surveyed all microbiology laboratories in England with Clinical Pathology
      Accreditation to determine standard operating procedures (SOPs) for urgent
      microscopy, culture and reporting of children's urine and to ascertain whether
      the SOPs facilitate compliance with NICE guidance. We undertook a computer search
      in six microbiology laboratories in south-west England to determine urine
      submissions and urine reports in children under 3 years. Seventy-three per cent
      of laboratories (110/150) participated. Enterobacteriaceae that were not E. coli
      were reported only as coliforms (rather than non-E. coli coliforms) by 61%
      (67/110) of laboratories. Eighty-eight per cent of laboratories (97/110) provided
      urgent microscopy for hospital and 54% for general practice (GP) paediatric
      urines; 61% of laboratories (confidence interval 52-70%) cultured 1 MUl volume of
      urine, which equates to one colony if the bacterial load is 106 c.f.u. l(-1).
      Only 22% (24/110) of laboratories reported non-E. coli coliforms and provided
      urgent microscopy for both hospital and GP childhood urines; only three
      laboratories also cultured a 5 MUl volume of urine. Only one of six laboratories
      in our submission audit had a significant increase in urine submissions and
      urines reported from children less than 3 years old between the predicted pre
      2007 level in the absence of guidance and the 2008 level following publication of
      the NICE guidance. Less than a quarter of laboratories were providing a service
      that would allow clinicians to fully comply with the first line recommendations
      in the 2007 NICE UTI in children guidance. Laboratory urine submission report
      figures suggest that the guidance has not led to an increase in diagnosis of UTI
      in children under 3 years old.

PMID- 26297551
TI  - Do consumers 'Get the facts'? A survey of alcohol warning label recognition in
      Australia.
AB  - BACKGROUND: There is limited research on awareness of alcohol warning labels and
      their effects. The current study examined the awareness of the Australian
      voluntary warning labels, the 'Get the facts' logo (a component of current
      warning labels) that directs consumers to an industry-designed informational
      website, and whether alcohol consumers visited this website. METHODS:
      Participants aged 18-45 (unweighted n = 561; mean age = 33.6 years) completed an
      online survey assessing alcohol consumption patterns, awareness of the 'Get the
      facts' logo and warning labels, and use of the website. RESULTS: No participants
      recalled the 'Get the facts' logo, and the recall rate of warning labels was 16%
      at best. A quarter of participants recognised the 'Get the facts' logo, and
      awareness of the warning labels ranged from 13.1-37.9%. Overall, only 7.3% of
      respondents had visited the website. Multivariable logistic regression models
      indicated that younger drinkers, increased frequency of binge drinking, consuming
      alcohol directly from the bottle or can, and support for warning labels were
      significantly, positively associated with awareness of the logo and warning
      labels. While an increased frequency of binge drinking, consuming alcohol
      directly from the container, support for warning labels, and recognition of the
      'Get the facts' logo increased the odds of visiting the website. CONCLUSIONS:
      Within this sample, recall of the current, voluntary warning labels on Australian
      alcohol products was non-existent, overall awareness was low, and few people
      reported visiting the DrinkWise website. It appears that current warning labels
      fail to effectively transmit health messages to the general public.

PMID- 26297552
TI  - Antiretroviral Pharmacokinetics in Pregnant Women.
AB  - For women infected with the human immunodeficiency virus (HIV) who become
      pregnant, the use of combination antiretroviral therapy (ART) significantly
      reduces transmission of HIV from mother to child. Selection of an appropriate ART
      regimen for use among pregnant women requires consideration of numerous factors
      including maternal and fetal safety, antiretroviral pharmacokinetics, and regimen
      efficacy. Optimization of antiretroviral pharmacokinetics during pregnancy
      requires special consideration because pregnancy-associated changes in drug
      absorption, distribution, metabolism, and excretion are known to occur throughout
      pregnancy and postpartum. Understanding antiretroviral placental transfer may
      offer additional insight into each drug's potential role in preventing HIV
      transmission in utero and may also have implications regarding viral resistance
      in cases where transmission does occur. In this review, we summarize key
      published data describing antiretroviral pharmacokinetics in pregnant women,
      providing suggestions for clinical application of these data where appropriate. 

PMID- 26297554
TI  - Identification of mutations in Colombian patients affected with Fabry disease.
AB  - Fabry Disease (FD) is an X-linked inborn error of glycosphingolipid catabolism,
      caused by a deficiency of the lisosomal alpha-galactosidase A (AGAL). The
      disorder leads to a vascular disease secondary to the involvement of kidney,
      heart and the central nervous system. The mutation analysis is a valuable tool
      for diagnosis and genetic counseling. Although more than 600 mutations have been
      identified, most mutations are private. Our objective was to describe the
      analysis of nine Colombian patients with Fabry disease by automated sequencing of
      the seven exons of the GLA gene. Two novel mutations were identified in two
      patients affected with the classical subtype of FD, in addition to other 6
      mutations previously reported. The present study confirms the heterogeneity of
      mutations in Fabry disease and the importance of molecular analysis for genetic
      counseling, female heterozygotes detection as well as therapeutic decisions. 

PMID- 26297555
TI  - Characterization of Pax3 and Pax7 genes and their expression patterns during
      different development and growth stages of Japanese pufferfish Takifugu rubripes.
AB  - Pax3 and Pax7 are the regulators and markers of muscle progenitors and satellite
      cells that contribute to the embryonic development and postembryonic growth of
      skeletal muscle in vertebrates, as well as to its repair and regeneration.
      However, information regarding them in vertebrate genome model, torafugu Takifugu
      rubripes, has remained unknown. Therefore, as an initial step, here we
      characterized Pax3 and Pax7 from torafugu and investigated their expression
      patterns during different developmental stages by RT-PCR. In silico analysis with
      the Fugu genome database (ver. 4.0) yielded two distinct genes each for Pax3
      (Pax3a and Pax3b) and Pax7 (Pax7a and Pax7b). The 75th amino acid, glutamine
      (Gln75), from the N-terminus was replaced by proline in the paired box domain
      (PD) of Pax3a. One single cDNA clone encoding Pax3a had deletion of Gln75 in PD,
      suggesting the presence of alternatively spliced variants (Q+/Q-). This was
      further supported by identification of two adjacent alternative 3' splice
      acceptor sites which produce Pax3b Q+ (aagCAGGGA) and Q- (aagcagGGA) variants.
      Interestingly, torafugu Pax7a, but not Pax7b, had an insert encoding five amino
      acid residues (SGEAS) in a C-terminal region of PD in two out of three cDNA
      clones. Genomic analysis showed two alternate splice donor sites at exon 4 of
      Pax7a. In synteny analysis, torafugu Pax3a showed syntenic relationship with the
      corresponding regions in other teleosts only, whereas Pax3b and Pax7b showed high
      syntenic relationship with the corresponding regions of both mammals and other
      teleosts. RT-PCR revealed that expression of Pax3a and Pax3b transcripts was
      restricted to embryonic stages only, whereas those of Pax7a and Pax7b was
      continued to be expressed in larvae and importantly those of Pax7a were found in
      adult skeletal muscles. Therefore, Pax3 appears to be most important for primary
      myogenesis and Pax7 for secondary myogenesis and growth by hyperplasia in fish.
      In this regard, the transcripts of torafugu Pax3 and Pax7 genes might be used for
      further investigation as a marker for identification of muscle precursor cells
      during different phases of growth, and this ambiguity is the next target of our
      research. 

PMID- 26297553
TI  - High-throughput methods for identification of protein-protein interactions
      involving short linear motifs.
AB  - Interactions between modular domains and short linear motifs (3-10 amino acids
      peptide stretches) are crucial for cell signaling. The motifs typically reside in
      the disordered regions of the proteome and the interactions are often transient,
      allowing for rapid changes in response to changing stimuli. The properties that
      make domain-motif interactions suitable for cell signaling also make them
      difficult to capture experimentally and they are therefore largely
      underrepresented in the known protein-protein interaction networks. Most of the
      knowledge on domain-motif interactions is derived from low-throughput studies,
      although there exist dedicated high-throughput methods for the identification of
      domain-motif interactions. The methods include arrays of peptides or proteins,
      display of peptides on phage or yeast, and yeast-two-hybrid experiments. We here
      provide a survey of scalable methods for domain-motif interaction profiling.
      These methods have frequently been applied to a limited number of ubiquitous
      domain families. It is now time to apply them to a broader set of peptide binding
      proteins, to provide a comprehensive picture of the linear motifs in the human
      proteome and to link them to their potential binding partners. Despite the
      plethora of methods, it is still a challenge for most approaches to identify
      interactions that rely on post-translational modification or context dependent or
      conditional interactions, suggesting directions for further method development. 

PMID- 26297557
TI  - Reply: ALDH18A1 gene mutations cause dominant spastic paraplegia SPG9: loss of
      function effect and plausibility of a dominant negative mechanism.

PMID- 26297558
TI  - ALDH18A1 gene mutations cause dominant spastic paraplegia SPG9: loss of function
      effect and plausibility of a dominant negative mechanism.

PMID- 26297556
TI  - Closing the tau loop: the missing tau mutation.
AB  - Frontotemporal lobar degeneration comprises a group of disorders characterized by
      behavioural, executive, language impairment and sometimes features of
      parkinsonism and motor neuron disease. In 1994 we described an Irish-American
      family with frontotemporal dementia linked to chromosome 17 associated with
      extensive tau pathology. We named this disinhibition-dementia-parkinsonism
      amyotrophy complex. We subsequently identified mutations in the MAPT gene. Eleven
      MAPT gene splice site stem loop mutations were identified over time except for 5'
      splice site of exon 10. We recently identified another Irish family with
      autosomal dominant early amnesia and behavioural change or parkinsonism
      associated with the 'missing' +15 mutation at the intronic boundary of exon 10.
      We performed a clinical, neuropsychological and neuroimaging study on the proband
      and four siblings, including two affected siblings. We sequenced MAPT and
      performed segregation analysis. We looked for a biological effect of the tau
      variant by performing real-time polymerase chain reaction analysis of RNA
      extracted from human embryonic kidney cells transfected with exon trapping
      constructs. We found a c.915+15A>C exon 10/intron 10 stem loop mutation in all
      affected subjects but not in the unaffected. The c.915+15A>C variant caused a
      shift in tau splicing pattern to a predominantly exon 10+ pattern presumably
      resulting in predominant 4 repeat tau and little 3 repeat tau. This strongly
      suggests that the c.915+15A>C variant is a mutation and that it causes
      frontotemporal dementia linked to chromosome 17 in this pedigree by shifting tau
      transcription and translation to +4 repeat tau. Tau (MAPT) screening should be
      considered in families where amnesia or atypical parkinsonism coexists with
      behavioural disturbance early in the disease process. We describe the final
      missing stem loop tau mutation predicted 15 years ago. Mutations have now been
      identified at all predicted sites within the 'stem' when the stem-loop model was
      first proposed and no mutations have been found within the 'loop' region as
      expected. Therefore we 'close the tau loop' having 'opened the loop' 21 years
      ago.

PMID- 26297559
TI  - Targeting the colony stimulating factor 1 receptor alleviates two forms of
      Charcot-Marie-Tooth disease in mice.
AB  - See Scherer (doi:10.1093/awv279) for a scientific commentary on this
      article.Charcot-Marie-Tooth type 1 neuropathies are inherited disorders of the
      peripheral nervous system caused by mutations in Schwann cell-related genes.
      Typically, no causative cure is presently available. Previous preclinical data of
      our group highlight the low grade, secondary inflammation common to distinct
      Charcot-Marie-Tooth type 1 neuropathies as a disease amplifier. In the current
      study, we have tested one of several available clinical agents targeting
      macrophages through its inhibition of the colony stimulating factor 1 receptor
      (CSF1R). We here show that in two distinct mouse models of Charcot-Marie-Tooth
      type 1 neuropathies, the systemic short- and long-term inhibition of CSF1R by
      oral administration leads to a robust decline in nerve macrophage numbers by ~70%
      and substantial reduction of the typical histopathological and functional
      alterations. Interestingly, in a model for the dominant X-linked form of Charcot
      Marie-Tooth type 1 neuropathy, the second most common form of the inherited
      neuropathies, macrophage ablation favours maintenance of axonal integrity and
      axonal resprouting, leading to preserved muscle innervation, increased muscle
      action potential amplitudes and muscle strengths in the range of wild-type mice.
      In another model mimicking a mild, demyelination-related Charcot-Marie-Tooth type
      1 neuropathy caused by reduced P0 (MPZ) gene dosage, macrophage blockade causes
      an improved preservation of myelin, increased muscle action potential amplitudes,
      improved nerve conduction velocities and ameliorated muscle strength. These
      observations suggest that disease-amplifying macrophages can produce multiple
      adverse effects in the affected nerves which likely funnel down to common
      clinical features. Surprisingly, treatment of mouse models mimicking Charcot
      Marie-Tooth type 1A neuropathy also caused macrophage blockade, but did not
      result in neuropathic or clinical improvements, most likely due to the late start
      of treatment of this early onset disease model. In summary, our study shows that
      targeting peripheral nerve macrophages by an orally administered inhibitor of
      CSF1R may offer a highly efficacious and safe treatment option for at least two
      distinct forms of the presently non-treatable Charcot-Marie-Tooth type 1
      neuropathies. 

PMID- 26297561
TI  - Occurrence and activity of a type II CRISPR-Cas system in Lactobacillus gasseri.
AB  - Bacteria encode clustered regularly interspaced short palindromic repeats
      (CRISPRs) and CRISPR-associated genes (cas), which collectively form an RNA
      guided adaptive immune system against invasive genetic elements. In silico
      surveys have revealed that lactic acid bacteria harbour a prolific and diverse
      set of CRISPR-Cas systems. Thus, the natural evolutionary role of CRISPR-Cas
      systems may be investigated in these ecologically, industrially, scientifically
      and medically important microbes. In this study, 17 Lactobacillus gasseri strains
      were investigated and 6 harboured a type II-A CRISPR-Cas system, with
      considerable diversity in array size and spacer content. Several of the spacers
      showed similarity to phage and plasmid sequences, which are typical targets of
      CRISPR-Cas immune systems. Aligning the protospacers facilitated inference of the
      protospacer adjacent motif sequence, determined to be 5'-NTAA-3' flanking the 3'
      end of the protospacer. The system in L. gasseri JV-V03 and NCK 1342 interfered
      with transforming plasmids containing sequences matching the most recently
      acquired CRISPR spacers in each strain. We report the distribution and function
      of a native type II-A CRISPR-Cas system in the commensal species L. gasseri.
      Collectively, these results open avenues for applications for bacteriophage
      protection and genome modification in L. gasseri, and contribute to the
      fundamental understanding of CRISPR-Cas systems in bacteria. 

PMID- 26297562
TI  - Polydrug use among nightclub patrons in a megacity: A latent class analysis.
AB  - BACKGROUND: Nightclubs are places with a high prevalence of binge drinking and
      illicit drug use. The aim of this study was to evaluate the characteristics of
      polydrug use, including licit and illicit drugs, among 2420 nightclub patrons in
      a probabilistic sample in the city of Sao Paulo, Brazil, METHODS: The study was
      conducted in 2013. A latent class analysis (LCA) of polydrug use, accounting for
      binge drinking (BD) and other drug use (cannabis, cocaine, ecstasy, tobacco,
      ketamine, inhalants and hallucinogens) in the past 12 months was performed using
      Mplus. Multinomial logistic regression was used to evaluate latent class
      associations with sociodemographic characteristics and variables that
      characterise type of nightclub and frequency of attendance. FINDINGS: A three
      class LCA model best described polydrug use patterns. We found a "no polydrug
      use" class (55%), a "moderate polydrug use" class (35%) and a "high level
      polydrug use" class (10%). Compared to "no polydrug use", patrons in the two
      "polydrug use classes" were more likely to be men, young adults (<34 years), have
      attended nightclubs three times or more per month and have attended hip-hop and
      rock music nightclubs. Patrons in the "high level polydrug use" class were more
      likely to attend electronic (aOR=9.9, 95% CI: 5.4-8.1, p<0.001) and hip-hop music
      nightclubs (aOR=10.1, 95% CI: 6.2-16.5, p<0.001). CONCLUSION: LCA is a useful
      method to identify groups of polydrug users among nightclub patrons. The three
      groups identified represented the diversity of patrons of Sao Paulo nightclubs.
      Frequency of attendance and the nightclub's musical style were highly correlated
      with polydrug use.

PMID- 26297560
TI  - Faulty cardiac repolarization reserve in alternating hemiplegia of childhood
      broadens the phenotype.
AB  - Alternating hemiplegia of childhood is a rare disorder caused by de novo
      mutations in the ATP1A3 gene, expressed in neurons and cardiomyocytes. As
      affected individuals may survive into adulthood, we use the term 'alternating
      hemiplegia'. The disorder is characterized by early-onset, recurrent, often
      alternating, hemiplegic episodes; seizures and non-paroxysmal neurological
      features also occur. Dysautonomia may occur during hemiplegia or in isolation.
      Premature mortality can occur in this patient group and is not fully explained.
      Preventable cardiorespiratory arrest from underlying cardiac dysrhythmia may be a
      cause. We analysed ECG recordings of 52 patients with alternating hemiplegia from
      nine countries: all had whole-exome, whole-genome, or direct Sanger sequencing of
      ATP1A3. Data on autonomic dysfunction, cardiac symptoms, medication, and family
      history of cardiac disease or sudden death were collected. All had 12-lead
      electrocardiogram recordings available for cardiac axis, cardiac interval,
      repolarization pattern, and J-point analysis. Where available, historical and
      prolonged single-lead electrocardiogram recordings during electrocardiogram
      videotelemetry were analysed. Half the cohort (26/52) had resting 12-lead
      electrocardiogram abnormalities: 25/26 had repolarization (T wave) abnormalities.
      These abnormalities were significantly more common in people with alternating
      hemiplegia than in an age-matched disease control group of 52 people with
      epilepsy. The average corrected QT interval was significantly shorter in people
      with alternating hemiplegia than in the disease control group. J wave or J-point
      changes were seen in six people with alternating hemiplegia. Over half the
      affected cohort (28/52) had intraventricular conduction delay, or incomplete
      right bundle branch block, a much higher proportion than in the normal population
      or disease control cohort (P = 0.0164). Abnormalities in alternating hemiplegia
      were more common in those >=16 years old, compared with those <16 (P = 0.0095),
      even with a specific mutation (p.D801N; P = 0.045). Dynamic, beat-to-beat or
      electrocardiogram-to-electrocardiogram, changes were noted, suggesting the
      prevalence of abnormalities was underestimated. Electrocardiogram changes
      occurred independently of seizures or plegic episodes. Electrocardiogram
      abnormalities are common in alternating hemiplegia, have characteristics
      reflecting those of inherited cardiac channelopathies and most likely amount to
      impaired repolarization reserve. The dynamic electrocardiogram and neurological
      features point to periodic systemic decompensation in ATP1A3-expressing organs.
      Cardiac dysfunction may account for some of the unexplained premature mortality
      of alternating hemiplegia. Systematic cardiac investigation is warranted in
      alternating hemiplegia of childhood, as cardiac arrhythmic morbidity and
      mortality are potentially preventable. 

PMID- 26297563
TI  - A matter of mind-set in the interpretation of forensic application.

PMID- 26297564
TI  - Defining populations and injecting parameters among people who inject drugs:
      Implications for the assessment of hepatitis C treatment programs.
AB  - There is considerable interest in determining the impact that increased uptake of
      treatment for hepatitis C virus (HCV) infection will have on the burden of HCV
      among people who inject drugs (PWID). An understanding of the size of the
      population of PWID, rates of injecting cessation and HCV prevalence and incidence
      within the PWID population is essential for such exercises. However, these
      parameters are often uncertain. In this paper we review methods for estimating
      the size of the population of PWID and related parameters, taking into account
      the uncertainty that exists around data on the natural history of injecting drug
      use; consider issues in the estimation of HCV prevalence among PWID; and consider
      the importance of opioid substitution therapy and prisons as settings for the
      prevention and treatment of HCV infection among PWID. These latter two points are
      illustrated through examples of ongoing work in England, Scotland and Australia.
      We conclude that an improved understanding of the size of PWID populations,
      including current and former PWID and parameters related to injecting drug use
      and settings where PWID may be reached, is necessary to inform HCV prevention and
      treatment strategies. 

PMID- 26297566
TI  - Spatiotemporally Distinct Interactions with Dendritic Cell Subsets Facilitates
      CD4+ and CD8+ T Cell Activation to Localized Viral Infection.
AB  - The dynamics of when and where CD4(+) T cells provide help for CD8(+) T cell
      priming and which dendritic cells (DCs) activate CD4(+) T cells in vivo after
      localized infection are poorly understood. By using a cutaneous herpes simplex
      virus infection model combined with intravital 2-photon imaging of the draining
      lymph node (LN) to concurrently visualize pathogen-specific CD4(+) and CD8(+) T
      cells, we found that early priming of CD4(+) T cells involved clustering with
      migratory skin DCs. CD8(+) T cells did not interact with migratory DCs and their
      activation was delayed, requiring later clustering interactions with LN-resident
      XCR1(+) DCs. CD4(+) T cells interacted with these late CD8(+) T cell clusters on
      resident XCR1(+) DCs. Together, these data reveal asynchronous T cell activation
      by distinct DC subsets and highlight the key role of XCR1(+) DCs as the central
      platform for cytotoxic T lymphocyte activation and the delivery of CD4(+) T cell
      help. 

PMID- 26297567
TI  - Health care providers' perspectives on a weekly text-messaging intervention to
      engage HIV-positive persons in care (WelTel BC1).
AB  - Though evidence shows that Mobile health (mHealth) interventions can improve
      adherence and viral load in HIV-positive persons, few have studied the health
      care providers' (HCP) perspective. We conducted a prospective mixed methods pilot
      study using the WelTel intervention wherein HIV-positive participants (n = 25)
      received weekly interactive text messages for 6 months. Text message response
      rate and topic data were collected to illustrate the HCP experience. The aim of
      this study is to explore intervention acceptability and feasibility from the HCP
      perspective through a baseline focus group and end of study interviews with HCP
      impacted by the intervention. Interview data were thematically coded using the
      Technology Acceptance Model. HCPs identified that the WelTel intervention engaged
      patients in building relationships, while organizing and streamlining existing
      mHealth efforts and dealing with privacy issues. HCPs recognized that although
      workload would augment initially, intervention benefits were many, and went
      beyond simply improving HIV viral load. 

PMID- 26297568
TI  - Methylomagnum ishizawai gen. nov., sp. nov., a mesophilic type I methanotroph
      isolated from rice rhizosphere.
AB  - An aerobic, methane-oxidizing bacterium (strain RS11D-PrT) was isolated from rice
      rhizosphere. Cells of strain RS11D-PrT were Gram-stain-negative, motile rods with
      a single polar flagellum and contained an intracytoplasmic membrane system
      typical of type I methanotrophs. The strain utilized methane and methanol as sole
      carbon and energy sources. It could grow at 20-37  degrees C (optimum 31-33 
      degrees C), at pH 6.8-7.4 (range 5.5-9.0) and with 0-0.2 % (w/v) NaCl (there was
      no growth at above 0.5 % NaCl). pmoA and mmoX genes were present. The ribulose
      monophosphate and/or ribulose bisphosphate pathways were used for carbon
      assimilation. Results of sequence analysis of 16S rRNA genes showed that strain
      RS11D-PrT is related closely to the genera Methylococcus, Methylocaldum,
      Methyloparacoccus and Methylogaea in the family Methylococcaceae. The similarity
      was low (94.6 %) between strain RS11D-PrT and the most closely related type
      strain (Methyloparacoccus murrellii R-49797T). The DNA G+C content was 64.1 mol%.
      Results of phylogenetic analysis of the pmoA gene and chemotaxonomic data
      regarding the major cellular fatty acids (C16 : 1omega7c, C16 : 0 and C14 : 0)
      and the major respiratory quinone (MQ-8) also indicated the affiliation of strain
      RS11D-PrT to the Methylococcus-Methylocaldum-Methyloparacoccus-Methylogaea clade.
      On the basis of phenotypic, genotypic and phylogenetic characteristics, strain
      RS11D-PrT is considered to represent a novel genus and species within the family
      Methylococcaceae, for which the name Methylomagnum ishizawai gen. nov., sp. nov.
      is proposed. The type strain is RS11D-PrT ( = JCM 18894T = NBRC 109438T = DSM
      29768T = KCTC 4681T).

PMID- 26297569
TI  - Somatic symptoms and psychological concerns in a general adolescent population:
      Exploring the relevance of DSM-5 somatic symptom disorder.
AB  - OBJECTIVE: DSM-5 somatic symptom disorder (SSD) constitutes a major change for
      psychosomatic medicine and psychiatry, as well as for epidemiological research in
      these fields. This study investigates somatic symptoms and psychological concerns
      among adolescents in order to systematically explore the relevance of SSD for
      general adolescent populations. METHODS: A cross-sectional population-based
      design, with a symptoms-based strategy and a symptom-and-psychological-concern
      based strategy, was used to estimate the prevalence of somatic symptoms and
      psychological concerns in a general adolescent population (n=2476, mean
      age=16years, 49% boys, 51% girls). Somatic symptoms and psychological concerns in
      relation to gender, and self-reported medical and psychiatric conditions were
      investigated. The association between somatic symptoms, psychological concerns,
      and functional impairment in school-, family-, peer- and physical activities was
      studied. RESULTS: Reporting 3+ persistent distressing somatic symptoms was
      significantly more common than reporting one or more persistent distressing
      somatic symptom(s) combined with serious psychological concern. The prevalence of
      such complaints was significantly higher in girls. The proportion of medical and
      psychiatric conditions was highest in the group reporting 3+ persistent
      distressing somatic symptoms combined with serious psychological concern.
      Belonging to this group most significantly increased odds ratios for functional
      impairment. CONCLUSION: For large-scale studies on SSD, results suggest the use
      of measures based on multiple somatic items in combination with psychological
      concerns, and a methodologically sound standardized measure of functional
      impairment. To further enhance clinical decision-making, the relation of symptoms
      to functional impairment, and the substantial overlap of SSD with medical and
      psychiatric conditions during adolescence should be addressed.

PMID- 26297570
TI  - Internal rib structure can be predicted using mathematical models: An anatomic
      study comparing the chest to a shell dome with application to understanding
      fractures.
AB  - The human rib cage resembles a masonry dome in shape. Masonry domes have a
      particular construction that mimics stress distribution. Rib cortical thickness
      and bone density were analyzed to determine whether the morphology of the rib
      cage is sufficiently similar to a shell dome for internal rib structure to be
      predicted mathematically. A finite element analysis (FEA) simulation was used to
      measure stresses on the internal and external surfaces of a chest-shaped dome.
      Inner and outer rib cortical thickness and bone density were measured in the mid
      axillary lines of seven cadaveric rib cages using computerized tomography
      scanning. Paired t tests and Pearson correlation were used to relate cortical
      thickness and bone density to stress. FEA modeling showed that the stress was 82%
      higher on the internal than the external surface, with a gradual decrease in
      internal and external wall stresses from the base to the apex. The inner cortex
      was more radio-dense, P < 0.001, and thicker, P < 0.001, than the outer cortex.
      Inner cortical thickness was related to internal stress, r = 0.94, P < 0.001,
      inner cortical bone density to internal stress, r = 0.87, P = 0.003, and outer
      cortical thickness to external stress, r = 0.65, P = 0.035. Mathematical models
      were developed relating internal and external cortical thicknesses and bone
      densities to rib level. The internal anatomical features of ribs, including the
      inner and outer cortical thicknesses and bone densities, are similar to the
      stress distribution in dome-shaped structures modeled using FEA computer
      simulations of a thick-walled dome pressure vessel. Fixation of rib fractures
      should include the stronger internal cortex.

PMID- 26297571
TI  - Expedited Programs for Serious Conditions: An Update on Breakthrough Therapy
      Designation.
AB  - PURPOSE: Our aim was to describe the regulatory pathways made available by the US
      Food and Drug Administration (FDA) to expedite the drug development and approval
      process, with a focus on the benefits and limitations of the Breakthrough Therapy
      Designation (BTD) pathway. METHODS: Published materials consisting of journal
      articles, press releases, government documents, and news articles from
      pharmaceutical publishers were identified through online databases (ie, Medline
      and Scopus), the FDA website, and Internet search engines (eg, Google). FINDINGS:
      To encourage pharmaceutical innovation and increase the number of products being
      approved each year, the FDA has introduced 4 expedited regulatory pathways to
      accelerate the drug development and approval process. The most recent program,
      enacted in July 2012, was BTD that is given to drugs that treat a serious or life
      threatening disease or condition; and preliminary clinical evidence suggests the
      potential for these drugs to provide a substantial improvement over the current
      standard of care. The primary basis for the creation of BTD is to provide
      patients with serious conditions with earlier access to FDA-approved medications.
      In 2014, 22% of the new molecular entities approved within the Center for Drug
      Evaluation and Research had BTD status, as opposed to only 11% in 2013, which
      indicates both the popularity and success of this expedited pathway.
      Additionally, the creation of BTD has produced a more collaborative working
      relationship between the pharmaceutical industry and the FDA because both parties
      have a vested interest in the drug's success. Some of the more notable concerns
      surrounding these approved breakthrough therapies have been the abbreviated
      tolerability and efficacy evidence available from accelerated clinical
      development programs, ensuring the manufacturing aspects keep pace with these
      accelerated clinical programs, and finally, managing the strain on resources for
      both the pharmaceutical companies and the FDA. IMPLICATIONS: BTD has already had
      many positive and negative impacts on various stakeholders, including sponsors,
      investors, regulatory agencies, third-party payors, and patients. The ultimate
      goal of the BTD program is to identify promising drug candidates early in the
      clinical development timeline, expedite the development and review processes via
      intensive guidance from the FDA, and provide patients access to approved
      therapies as quickly as possible. With the first few batches of BTD product
      approvals, the FDA and other stakeholders have been working collaboratively to
      address the various expected and unexpected challenges that have arisen during
      the BTD process in order to refine and improve this already successful program.

PMID- 26297572
TI  - Emoticon use Increases Plain Milk and Vegetable Purchase in a School Cafeteria
      without Adversely Affecting Total Milk Purchase.
AB  - PURPOSE: Choosing poor-quality foods in school cafeterias is a risk factor for
      childhood obesity. Given the option, children often select chocolate milk over
      plain white milk. Efforts to increase plain white milk selection, such as banning
      chocolate milk in school cafeterias, increases plain white fat-free milk (PWFFM)
      purchase but decreases the overall milk purchase. The purpose of this study was
      to determine whether emoticon placement next to healthful foods would increase
      healthful purchases, particularly PWFFM. METHODS: In an inner city elementary
      school with 297 children, "Green Smiley Face" emoticons were placed to encourage
      the purchase of healthful foods including an entree with whole grains, fruits,
      vegetables, and PWFFM. Purchase data were obtained from cash register receipts.
      Differences were analyzed by chi(2) Care and Statistical Process Control (SPC)
      and Graphical Methods. RESULTS: Only 7.4% of students selected white milk at
      baseline compared with 17.9% after the emoticons were placed (P < 0.0001). There
      was a decrease in chocolate milk purchase from 86.5% to 77.1% with the addition
      of the emoticons (P < 0.001). There was no significant difference in total milk
      purchase: 93.4% before the emoticons compared with 94.9% after. There was no
      significant change in the purchase of entree or fruits. However, there was, a
      significant increase in vegetable purchase from 0.70 vegetables purchased per
      student per day to 0.90 by SPC (>8 points above the mean). IMPLICATIONS: The
      addition of emoticons increases the purchase of PWFFM and vegetables in a school
      cafeteria setting without adversely affecting total milk sales. Emoticons offer a
      practical, low-cost means to improve food selection by children.

PMID- 26297573
TI  - Terasakiispira papahanaumokuakeensis gen. nov., sp. nov., a gammaproteobacterium
      from Pearl and Hermes Atoll, Northwestern Hawaiian Islands.
AB  - A Gram-negative, helical bacterium designated PH27AT was cultivated from an
      anchialine pool on Pearl and Hermes Atoll, Northwestern Hawaiian Islands. The
      obligately halophilic strain was motile by bipolar tufts of flagella and grew
      optimally at pH 7, and microaerobically or aerobically. Closest neighbours based
      on 16S rRNA gene nucleotide sequence identity are Marinospirillum celere v1c_Sn
      redT (93.31 %) and M. alkaliphilum Z4T (92.10 %) in the family
      Oceanospirillaceae, class Gammaproteobacteria. PH27AT is distinguished
      phenotypically from members of the genus Marinospirillum by its hydrolysis of
      gelatin, the absence of growth in media containing <= 1 % (w/v) NaCl and the
      ranges of temperature (12-40  degrees C) and pH (5-8) for growth. The major
      compound ubiquinone Q-9 distinguishes the quinone system of strain PH27AT from
      those in members of the genus Marinospirillum and other members of the
      Oceanospirillaceae, in which the major quinone is Q-8. Major polar lipids in
      PH27AT were phosphatidylethanolamine and phosphatidylglycerol, with moderate
      amounts of diphosphatidylglycerol and phosphatidylserine. Spermidine and
      cadaverine dominated the polyamine pattern; large proportions of cadaverine have
      not been reported in members of the genus Marinospirillum. Genotypic and
      chemotaxonomic data show that PH27AT does not belong in the genus Marinospirillum
      or other genera of the family Oceanospirillaceae or the Halomonadaceae. We
      propose a new genus, Terasakiispira gen. nov., be created to accommodate
      Terasakiispira papahanaumokuakeensis gen. nov., sp. nov. as the type species,
      with PH27AT ( = ATCC BAA-995T = DSM 16455T = DSM 23961T) as the type strain.

PMID- 26297575
TI  - Camelimonas fluminis sp. nov., a cyhalothrin-degrading bacterium isolated from
      river water.
AB  - An aerobic, Gram-stain-negative, short rod-shaped, non-spore-forming, cyhalothrin
      degrading bacterial strain, XZ2(T), was isolated from the surface water of
      Hanjiang River in Wuhan, China. Strain XZ2(T) grew optimally at pH 6.0, 30 
      degrees C and in the absence of NaCl. The G+C content of the total DNA was 64.1
      mol%. The 16S rRNA gene sequence of strain XZ2(T) showed the highest similarity
      to that of Camelimonas lactis M 2040(T) (99.1%), followed by Camelimonas abortus
      UK34/07-5(T) (95.9%) and Chelatococcus daeguensis K106(T) (95.3%). The major
      cellular fatty acids of strain XZ2(T) were C19 : 0 cyclo omega8c (63.1%), C16 : 0
      (15.0%) and C18 : 1omega7c/C18 : 1omega6c (summed feature 8; 8.9%). C18 : 0 3-OH
      was also detected as the major hydroxylated fatty acid. The respiratory quinone
      was ubiquinone Q-10. The polar lipid profile included the major compounds
      phosphatidylcholine and diphosphatidylglycerol, and moderate amounts of
      phosphatidylethanolamine, phosphatidylglycerol and two unidentified aminolipids.
      The predominant compound in the polyamine pattern was spermidine. These
      chemotaxonomic data supported the affiliation of strain XZ2(T) to the genus
      Camelimonas. The DNA-DNA hybridization value between strain XZ2(T) and
      Camelimonas lactis M 2040(T) was 43.5 +/- 0.6%. DNA-DNA hybridization data as
      well as biochemical and physiological characteristics strongly supported the
      genotypic and phenotypic differentiations between strain XZ2(T) and Camelimonas
      lactis M 2040(T). Therefore, strain XZ2(T) represents a novel species of the
      genus Camelimonas, for which the name Camelimonas fluminis sp. nov. is proposed.
      The type strain is XZ2(T) ( = KCTC 42282(T) = ACCC 19738(T)).

PMID- 26297574
TI  - Topical clobetasol for the treatment of toxic epidermal necrolysis: study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: Toxic epidermal necrolysis (TEN) is a rare systemic allergic drug
      eruption with high patient mortality. Currently, no established treatments have
      been shown to be effective for TEN beyond supportive care. Prior studies of
      systemic corticosteroids have yielded conflicting data, with some showing a
      possible benefit and others reporting in increased mortality. However, topical
      steroids have shown promise for treatment of ocular sequelae of TEN, such as
      scarring and vision loss. We have designed a randomized controlled trial to
      evaluate topical clobetasol for treatment of the epidermal manifestations of TEN.
      In addition, we propose genetic studies to characterize the TEN transcriptome and
      alterations in cutaneous gene expression that might occur following topical
      steroid treatment. METHODS/DESIGN: This split-body randomized, double-blind,
      placebo-controlled Phase IIa proof-of-concept trial will evaluate the safety and
      efficacy of once-daily topical clobetasol applied to the skin of patients with
      TEN. This multicenter trial will recruit a total of 15 patients between the ages
      of 12 and 85 from the University of California Davis Medical Center and Shriners
      Hospital for Children inpatient burn units. Designated treatment areas on
      opposite sides of the body will be treated with blinded clobetasol 0.05% ointment
      or control petrolatum ointment daily for 14 days. On day 3 of therapy, a biopsy
      will be taken from the treated area for genetic studies. The primary study aims
      will be to establish the safety of topical clobetasol treatment and determine the
      time to cessation of skin detachment for the control and clobetasol-treated
      areas. Secondary endpoints will evaluate efficacy using parameters such as time
      to 90% re-epithelialization and percentage of affected skin at 0, 3, 6, 9, 12 and
      15 days. Genomic DNA and RNA will be obtained from biopsy samples, to
      characterize the TEN transcriptome and identify changes in gene expression after
      topical steroid treatment. DISCUSSION: Topical steroids have shown promise for
      treating ocular complications of TEN, but to date have not been evaluated for
      cutaneous manifestations of the disease. This trial will investigate clinical and
      molecular outcomes of topical clobetasol application and hopefully provide
      insight into the disease pathophysiology. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT02319616. https://clinicaltrials.gov/ct2/show/NCT02351037.

PMID- 26297577
TI  - Antiviral immunity in marine molluscs.
AB  - Marine molluscs, like all living organisms, are constantly exposed to viruses and
      have evolved efficient antiviral defences. We review here recent developments in
      molluscan antiviral immunity against viruses belonging to the order
      Herpesvirales. Emerging results suggest an interferon-like response and autophagy
      are involved in the antiviral defence of bivalves to viral infection. Multi
      functional plasma proteins from gastropods and bivalves have been identified to
      have broad-spectrum antiviral activity against mammalian viruses. The antiviral
      defences present in molluscs can be enhanced by genetic selection, as shown by
      the presence of oyster strains specifically resistant to ostreid herpesvirus type
      1. Whether varying amounts or different isoforms of these antiviral plasma
      proteins contributes to genetic resistance is worthy of further research. Other
      evolutionarily conserved antiviral mechanisms, such as RNA interference and
      apoptosis, still need further characterization. 

PMID- 26297576
TI  - Molecular epidemiology study of Mycobacterium tuberculosis and its susceptibility
      to anti-tuberculosis drugs in Indonesia.
AB  - BACKGROUND: Genotyping of Mycobacterium tuberculosis helps to understand the
      molecular epidemiology of tuberculosis and to address evolutionary questions
      about the disease spread. Certain genotypes also have implications for the spread
      of infection and treatment. Indonesia is a very diverse country with a population
      with multiple ethnicities and cultures and a history of many trade and tourism
      routes. This study describes the first attempt to map the molecular epidemiology
      of TB in the Indonesian archipelago. METHOD: From 2008 to 2011, 404 clinical
      specimens from sputum-smear (SS+) TB patients, age >=15 years, were collected
      from 16 TB referral primary health centers (PHC) in 16 provincial capitals in
      Indonesia. Susceptibility testing to first line drugs was conducted for 262
      samples using the agar proportion method as per WHO guidelines. Spoligotyping was
      done on all samples. RESULTS: Ninety-three of the 404 samples (23 %) were from
      the Beijing family, making it the predominant family in the country. However, the
      geographic distribution of the family varied by region with 86/294 (29.3 %) in
      the western region, 6/72 (8.3 %) in the central region, and 2/72 (2.8 %) in the
      eastern region (p < 0.001). The predominant genotype in the central and eastern
      regions was from the East-African-Indian (EAI) family, comprising 15.3 % (11/72),
      and 26.3 % (10/38) of the isolates, respectively. Drug susceptibility to first
      line anti-TB drugs was tested in 262 isolates. 162 (61.8 %) isolates were
      susceptible to all TB drugs, 70 (26.7 %) were mono-resistant 16 (6.1 %) were poly
      resistant, and 14 (5.4 %) were multi-drug resistant (MDR). The proportion of
      Beijing family isolates in the susceptible, mono-resistant, poly-resistant, and
      MDR groups was 33/162 (20.4 %), 28/70 (40.0 %), 6/16 (37.5 %), and 3/14 (21.4 %),
      respectively. Overall, resistance of the Beijing family isolates to any of the
      first line TB drugs was significantly higher than non-Beijing families [37/71
      (52.1 %) vs. 63/191 (33.0 %) (p-value = 0.003)]. CONCLUSION: The distribution of
      Mycobacterium tuberculosis genotypes in Indonesia showed high genetic diversity
      and tended to vary by geographic regions. Drug susceptibility testing confirmed
      that the Beijing family of M.tb in Indonesia exhibited greater resistance to
      first line anti-TB drugs than did other families.

PMID- 26297578
TI  - Pantoea theicola sp. nov., isolated from black tea.
AB  - A Gram-negative, facultatively anaerobic strain was isolated from black tea. On
      the basis of 16S rRNA gene sequence similarity comparisons, strain QC88-366T was
      grouped into the genus Pantoea, being related most closely to the type strains of
      Pantoea gaviniae (98.5 %) and Pantoea calida (98.3 %); sequence similarities were
      <= 97.0 % to the type strains of other species of the genus Pantoea. Multilocus
      sequence analysis based on partial sequences of the gyrB, rpoB, infB and atpD
      genes also revealed P. gaviniae and P. calida as the closest phylogenetic
      relatives. The fatty acid profile showed the major fatty acids of strain QC88
      366T were C16 : 0, C16 : 1 and C18 : 1, the same as those of its closest related
      species. However, the ratio of C16 : 1, C17 : 0 cyclo, C18 : 1 and C18 : 2
      differed slightly compared with those of the related neighbours. In addition, the
      results of physiological and biochemical tests also allowed the phenotypic
      differentiation of strain QC88-366T from its closest phylogenetic neighbours. The
      G+C content of the DNA was 57.2 mol%. Strain QC88-366T therefore represents a
      novel species of the genus Pantoea, for which the name Pantoea theicola sp. nov.
      is proposed. The type strain is QC88-366T ( = DSM 29212T = NBRC 110557T). 

PMID- 26297579
TI  - Nocardiopsis oceani sp. nov. and Nocardiopsis nanhaiensis sp. nov., actinomycetes
      isolated from marine sediment of the South China Sea.
AB  - Two actinomycete strains, designated 10A08AT and 10A08BT, were isolated from
      marine sediment samples of the South China Sea and their taxonomic positions were
      determined by a polyphasic approach. The two Gram-stain-positive, aerobic strains
      produced branched substrate mycelium and aerial hyphae, and no diffusible pigment
      was produced in the media tested. At maturity, spore chains were formed on aerial
      hyphae and all mycelium fragmented with age. Whole-cell hydrolysates of both
      strains contained meso-diaminopimelic acid and no diagnostic sugars. Their
      predominant menaquinones (>10 %) were MK-9(H4), MK-9(H6) and MK-10(H6) for strain
      10A08AT and MK-9(H4), MK-9(H6), MK-10(H4) and MK-10(H6) for strain 10A08BT. The
      polar lipids detected from the two strains were diphosphatidylglycerol,
      phosphatidylglycerol, phosphatidylcholine and unknown phosphoglycolipids and
      phospholipids. The major fatty acids (>10 %) of both strains were iso-C16 : 0 and
      summed feature 4 (iso-C17 : 1 I and/or anteiso-C17 : 1 B). The genomic DNA G+C
      contents of strains 10A08AT and 10A08BT were 70.9 and 71.6 mol%, respectively. On
      the basis of 16S rRNA gene sequence similarities, the two strains were shown to
      be most closely related to species of the genus Nocardiopsis. DNA-DNA
      hybridization relatedness values of < 70 % between these two isolates and their
      closest neighbour, Nocardiopsis terrae YIM 90022T, and between the two strains
      supported the conclusion that they represent two novel species. Based on
      phylogenetic analysis and phenotypic and genotypic data, it is concluded that the
      two isolates belong to the genus Nocardiopsis, and the names Nocardiopsis oceani
      sp. nov. (type strain 10A08AT = DSM 45931T = BCRC 16951T) and Nocardiopsis
      nanhaiensis sp. nov. (type strain 10A08BT = CGMCC 47227T = BCRC 16952T) are
      proposed.

PMID- 26297580
TI  - Transcriptional activation of Epstein-Barr virus BRLF1 by USF1 and Rta.
AB  - During its lytic cycle, Epstein-Barr virus (EBV) expresses Rta, a factor encoded
      by BRLF1 that activates the transcription of viral lytic genes. We found that
      upstream stimulating factor (USF) binds to E1, one of the five E boxes located at
      - 79 in the BRLF1 promoter (Rp), to activate BRLF1 transcription. Furthermore,
      Rta was shown to interact with USF1 in coimmunoprecipitation and glutathione S
      transferase (GST)-pulldown assays, and confocal laser-scanning microscopy further
      confirmed that these two proteins colocalize in the nucleus. Rta was also found
      to bind with the E1 sequence in a biotin-labelled E1 probe, but only in the
      presence of USF1, suggesting that these two proteins likely form a complex on E1.
      We subsequently constructed p188mSZ, a reporter plasmid that contained the
      sequence from - 188 to +5 in Rp, within which the Sp1 site and Zta response
      element were mutated. In EBV-negative Akata cells cotransfected with p188mSZ and
      plasmids expressing USF1 and Rta, synergistic activation of Rp transcription was
      observed. However, after mutating the E1 sequence in p188mSZ, USF1 and Rta were
      no longer able to transactivate Rp, indicating that Rta autoregulates BRLF1
      transcription via its interaction with USF1 on E1. This study showed that pUSF1
      transfection after EBV lytic induction in P3HR1 cells increases Rta expression,
      indicating that USF1 activates Rta expression after the virus enters the lytic
      cycle. Together, these results reveal a novel mechanism by which USF interacts
      with Rta to promote viral lytic development, and provide additional insight into
      the viral-host interactions of EBV. 

PMID- 26297581
TI  - Photo-isomerization and oxidation of bilirubin in mammals is dependent on albumin
      binding.
AB  - The bilirubin (BR) photo-conversion in the human body is a protein-dependent
      process; an effective photo-isomerization of the potentially neurotoxic Z,Z-BR as
      well as its oxidation to biliverdin in the antioxidant redox cycle is possible
      only when BR is bound on serum albumin. We present a novel analytical concept in
      the study of linear tetrapyrroles metabolic processes based on an in-depth
      mapping of binding sites in the structure of human serum albumin (HSA). A
      combination of fluorescence spectroscopy, circular dichroism (CD) spectroscopy,
      and molecular modeling methods was used for recognition of the binding site for
      BR, its derivatives (mesobilirubin and bilirubin ditaurate), and the products of
      the photo-isomerization and oxidation (lumirubin, biliverdin, and xanthobilirubic
      acid) on HSA. The CD spectra and fluorescent quenching of the Trp-HSA were used
      to calculate the binding constants. The results of the CD displacement
      experiments performed with hemin were interpreted together with the findings of
      molecular docking performed on the pigment-HSA complexes. We estimated that Z,Z
      BR and its metabolic products bind on two independent binding sites. Our findings
      support the existence of a reversible antioxidant redox cycle for BR and explain
      an additional pathway of the photo-isomerization process (increase of HSA binding
      capacity; the excess free [unbound] BR can be converted and also bound to HSA). 

PMID- 26297582
TI  - Short-term high glucose exposure impairs insulin signaling in endothelial cells.
AB  - BACKGROUND: Hyperglycemia is the hallmark of diabetes and its cardiovascular
      complications. Insulin plays an important role in the regulation of vascular
      homeostasis and maintenance of endothelial function. Insulin signaling occurs
      after binding to the insulin receptor, causing activation of two separate and
      parallel pathways: PI3K/AKT/eNOS and Ras/Raf/MAPK pathways. AKT phosphorylates
      eNOS at Ser1177, resulting in increased nitric oxide production and vasodilation.
      The MAPK pathway results in endothelin-1 production and vasoconstriction and
      mitogenic effects. METHODS: We studied the effects of physiological insulin
      treatment in human umbilical vein endothelial cells (HUVECs) on the two pathways
      under high glucose conditions, which mimic the in vivo condition of
      hyperglycemia. HUVECs were incubated with insulin at different physiological
      concentrations (from 10(-10) to 10(-8) M) for 30 min after 24 h of exposition to
      normal (5 mmol/L, NG) or high glucose (25 mmol/L, HG). Phosphorylated forms of
      AKT, eNOS, ERK1/2, p38, JNK and insulin receptor-beta subunit (IRbeta) were
      evaluated. RESULTS: In normal glucose, the active phosphorylated forms of AKT,
      eNOS, ERK1/2, p38 and JNK were increased in insulin treated cells, in a dose
      dependent manner. In high glucose, insulin was not able to activate the
      PI3K/AKT/eNOS pathway, with the phosphorylated form of eNOS reduced with respect
      to the control. However, insulin was able to induce the up-regulation of phospho
      ERK1/2, -p38 and -JNK. Moreover, we found reduced levels of IRbeta phosphorylated
      form in high glucose as compared to the control. Insulin was able to increase
      phospho-IRbeta in normal glucose but not in high glucose, in which the total
      protein levels remained reduced. CONCLUSIONS: Exposure to short-term high glucose
      negatively affects insulin signaling even when physiological insulin
      concentrations are added. The impairment of the PI3K/AKT/eNOS pathway after
      physiological insulin treatment could contribute to detrimental effects on
      cardiovascular homeostasis under high glucose conditions, and might shift toward
      the activation of certain mitogenic effectors, such as ERK1/2, p38 and JNK, the
      only ones that respond to physiological insulin treatment in high glucose.

PMID- 26297583
TI  - Structural design of contact lens-based drug delivery systems; in vitro and in
      vivo studies of ocular triggering mechanisms.
AB  - This study identifies and investigates the potential use of in-eye trigger
      mechanisms to supplement the widely available information on release of
      ophthalmic drugs from contact lenses under passive release conditions. Ophthalmic
      dyes and surrogates have been successfully employed to investigate how these
      factors can be drawn together to make a successful system. The storage of a drug
      containing lens in a pH lower than that of the ocular environment can be used to
      establish an equilibrium that favours retention of the drug in the lens prior to
      ocular insertion. Although release under passive conditions does not result in
      complete dye elution, the use of mechanical agitation techniques which mimic the
      eyelid blink action in conjunction with ocular tear chemistry promotes further
      release. In this way differentiation between passive and triggered in vitro
      release characteristics can be established. Investigation of the role of
      individual tear proteins revealed significant differences in their ability to
      alter the equilibrium between matrix-held and eluate-held dye or drug. These
      individual experiments were then investigated in vivo using ophthalmic dyes.
      Complete elution was found to be achievable in-eye; this demonstrated the
      importance of that fraction of the drug retained under passive conditions and the
      triggering effect of in-eye conditions on the release process. Understanding both
      the structure-property relationship between drug and material and in-eye trigger
      mechanisms, using ophthalmic dyes as a surrogate, provides the basis of knowledge
      necessary to design ocular drug delivery vehicles for in-eye release in a
      controllable manner. 

PMID- 26297584
TI  - The oral microbiome in human immunodeficiency virus (HIV)-positive individuals.
AB  - Human immunodeficiency virus (HIV) infection is associated with a range of oral
      conditions, and increased numbers of disease-associated microbial species have
      previously been found in HIV-positive subjects. The aim of this study was to use
      next-generation sequencing to compare the composition of the oral microbiome in
      HIV-positive and -negative individuals. Plaque and saliva were collected from 37
      HIV-positive individuals and 37 HIV-negative individuals, and their bacterial
      composition determined by pyrosequencing of partial 16S rRNA genes. A total of
      855,222 sequences were analysed. The number of species-level operational
      taxonomic units (OTUs) detected was significantly lower in the saliva of HIV
      positive individuals (mean = 303.3) than in that of HIV-negative individuals
      (mean = 365.5) (P < 0.0003). Principal coordinates analysis (PCoA) based on
      community membership (Jaccard index) and structure (Yue and Clayton measure of
      dissimilarity) showed significant separation of plaque and saliva samples
      [analysis of molecular variance (AMOVA), P < 0.001]. PCoA plots did not show any
      clear separation based on HIV status. However, AMOVA indicated that there was a
      significant difference in the community membership of saliva between HIV-positive
      and -negative groups (P = 0.001). Linear discriminant analysis effect size
      revealed an OTU identified as Haemophilus parainfluenzae to be significantly
      associated with HIV-positive individuals, whilst Streptococcus mitis/HOT473 was
      most significantly associated with HIV-negative individuals. In conclusion, this
      study has confirmed that the microbial composition of saliva and plaque is
      different. The oral microbiomes of HIV-positive and -negative individuals were
      found to be similar overall, although there were minor but significant
      differences in the composition of the salivary microbiota of the two groups.

PMID- 26297586
TI  - Editor's Note.

PMID- 26297585
TI  - Methylocapsa palsarum sp. nov., a methanotroph isolated from a subArctic
      discontinuous permafrost ecosystem.
AB  - An aerobic methanotrophic bacterium was isolated from a collapsed palsa soil in
      northern Norway and designated strain NE2T. Cells of this strain were Gram-stain
      negative, non-motile, non-pigmented, slightly curved thick rods that multiplied
      by normal cell division. The cells possessed a particulate methane monooxygenase
      enzyme (pMMO) and utilized methane and methanol. Strain NE2T grew in a wide pH
      range of 4.1-8.0 (optimum pH 5.2-6.5) at temperatures between 6 and 32  degrees C
      (optimum 18-25  degrees C), and was capable of atmospheric nitrogen fixation
      under reduced oxygen tension. The major cellular fatty acids were C18 : 1omega7c,
      C16 : 0 and C16 : 1omega7c, and the DNA G+C content was 61.7 mol%. The isolate
      belonged to the family Beijerinckiaceae of the class Alphaproteobacteria and was
      most closely related to the facultative methanotroph Methylocapsa aurea KYGT
      (98.3 % 16S rRNA gene sequence similarity and 84 % PmoA sequence identity).
      However, strain NE2T differed from Methylocapsa aurea KYGT by cell morphology,
      the absence of pigmentation, inability to grow on acetate, broader pH growth
      range, and higher tolerance to NaCl. Therefore, strain NE2T represents a novel
      species of the genus Methylocapsa, for which we propose the name Methylocapsa
      palsarum sp. nov. The type strain is NE2T ( = LMG 28715T = VKM B-2945T).

PMID- 26297587
TI  - Beyond Versailles: Recovering the Voices of-Nurses in Post-World War I U.S.
      European Relations.
AB  - From late 1918 to 1922, the American Red Cross (ARC) enlisted roughly six hundred
      American nurses and scores of female auxiliary staff to labor in post-World War I
      continental Europe, Russia, and the Near East, mostly stationed in Poland,
      Czechoslovakia, the Balkan states, and Siberia. The ARC nurses ran health
      clinics, made home visits, and opened nurse training schools. Close readings of
      letters, diaries, official reports, and published articles help recover the place
      of these women in postwar European history and the history of U.S. foreign
      relations. Their writings reveal their perceptions about eastern European and
      Russian politics and culture, their assumptions about the proper U.S. role in the
      region's affairs, and their efforts to influence popular U.S. discourse on these
      topics. This article argues that American nurses and support staff are central
      yet neglected-players in the history of U.S.-European affairs. Through its bottom
      up approach, it offers a more personal and intimate perspective on the history of
      U.S. international relations during this time. 

PMID- 26297588
TI  - Midwife and Public Health Nurse Tatsuyo Amari and a State-Endorsed Birth Control
      Campaign in 1950s Japan.
AB  - Mrs. Tatsuyo Amari, a qualified midwife and nurse, served Japan's state-endorsed
      birth control campaign as a "birth control field instructor" in rural Minamoto
      Village of Yamanashi Prefecture just west of Tokyo. Her work sheds light on the
      role of female health-care workers in health and population governance in 1950s
      Japan. Amari not only facilitated the "top-down" transfer of the state-sanctioned
      idea of birth control and contraceptives, as did other birth control field
      instructors, but also enabled the "bottom-up" flow of knowledge about people's
      reproductive lives through her participation in the policy-oriented birth control
      research called the "three model-village study." Contextualizing Amari's
      engagement with the study elucidates how the state relied on the established role
      of female health-care workers as intermediaries between the state and the people.
      Finally, Amari's contribution to the scientific aspect of the campaign may
      motivate historians to recognize the politics around the participation of female
      health-care workers in the science of birth control. 

PMID- 26297589
TI  - Considering the History of Interprofessional Education and Practice in the United
      States.

PMID- 26297590
TI  - Teamwork: Metaphors and Myths of Equality in the Health-Care Setting.

PMID- 26297591
TI  - An Unexpected but Fruitful Combination.

PMID- 26297592
TI  - Interdisciplinary Interprofessionalism at Mid-Century: Ancel Keys, Human Biology,
      and the Laboratory of Physiological Hygiene, 1940-1950.

PMID- 26297593
TI  - Clinical Pharmacy: An Example of Interprofessional Education in the Late 1960s
      and 1970s.

PMID- 26297594
TI  - Nurses, Doctors, and the Cardiac Arrest Paradigm: A Collaborative Endeavor.

PMID- 26297595
TI  - Interprofessional Learning: An Old Idea in a New Package.

PMID- 26297597
TI  - Streptomonospora halotolerans sp. nov., an actinomycete isolated from soil.
AB  - A novel actinomycete, designated strain NEAU-Jh2-17(T), was isolated from muddy
      soil collected from a riverbank in Jilin Province, northern China, and
      characterized using a polyphasic approach. The 16S rRNA gene sequence of strain
      NEAU-Jh2-17(T) showed highest similarity to those of Streptomonospora nanhaiensis
      12A09(T) (99.26%), Nocardiopsis rosea YIM 90094(T) (97.31%), Streptomonospora
      halophila YIM 91355(T )(97.24%) and Streptomonospora arabica S186(T) (97.02%).
      Phylogenetic analysis based on 16S rRNA gene sequences demonstrated that strain
      NEAU-Jh2-17(T) fell within a cluster consisting of the type strains of species of
      the genus Streptomonospora and formed a stable clade with S. nanhaiensis 12A09(T)
      in trees generated with two algorithms. Key morphological and chemotaxonomic
      properties also confirmed the affiliation of strain NEAU-Jh2-17(T) to the genus
      Streptomonospora. The cell wall contained meso-diaminopimelic acid as the
      diagnostic diamino acid and whole-cell hydrolysates contained glucose, ribose and
      galactose. The polar lipids were diphosphatidylglycerol (DPG),
      phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylcholine
      (PC), phosphatidylinositol (PI), phosphatidylinositol mannoside (PIM), two
      unknown phospholipids (PLs) and two unknown glycolipids (GLs). The predominant
      menaquinones were MK-10(H2), MK-10(H8), MK-10(H6) and MK-10(H4). Major fatty
      acids were C18 : 0 10-methyl, anteiso-C17 : 0, C16 : 0 10-methyl, iso-C15 : 0,
      C17 : 0 10-methyl and C18 : 0. The DNA G+C content was 71.82 mol%. However, a
      combination of DNA-DNA hybridization results and some phenotypic characteristics
      demonstrated that strain NEAU-Jh2-17(T) could be distinguished from its closely
      related relatives. Therefore, strain NEAU-Jh2-17(T) is considered to represent a
      novel species of the genus Streptomonospora, for which the name Streptomonospora
      halotolerans sp. nov. is proposed. The type strain is NEAU-Jh2-17(T) ( = CGMCC
      4.7218(T) = JCM 30347(T)).

PMID- 26297598
TI  - A Randomized Controlled Trial of the Food Dudes Program: Tangible Rewards are
      More Effective Than Social Rewards for Increasing Short- and Long-Term Fruit and
      Vegetable Consumption.
AB  - BACKGROUND: Despite many health benefits, children do not consume enough fruits
      and vegetables (F/V). The Food Dudes program increases in-school F/V consumption,
      but the cost of prizes might be an adoption barrier. OBJECTIVE: Our aim was to
      compare the effects of the Food Dudes program when prizes vs praise are used to
      reward F/V consumption. DESIGN: We conducted a randomized controlled trial with
      three groups (ie, prize, praise, and control). Schools were randomly assigned to
      groups while approximately equating the percentage of students qualifying for
      free or reduced-price lunch. F/V consumption (lunch-tray photos) was assessed
      twice at pre-intervention and once after phase I, phase II, and at 6 months post
      intervention, spanning approximately 11 months overall. PARTICIPANTS/SETTING: In
      total, 2,292 students attending six elementary schools participated, with 882,
      640, and 770 in the prize, praise, and control groups, respectively.
      INTERVENTION: The Food Dudes program was implemented over 4.5 months in all but
      the control schools. Two Food Dudes schools implemented the program with tangible
      prizes contingent on individual students' F/V consumption (prize group); two
      schools implemented Food Dudes using teacher praise instead of prizes (praise
      group). Follow-up data were collected 6 months post-intervention. MAIN OUTCOME
      MEASURE: F/V consumption was assessed by digital imaging of lunch trays.
      STATISTICAL ANALYSIS PERFORMED: Linear mixed-effects modeling, including sex,
      grade, and baseline consumption as covariates, was performed. RESULTS: Students
      attending the Food Dudes schools consumed more F/V than control schools after
      phase I, with larger differences in prize schools (92% difference) than praise
      schools (50% difference). After phase II, Food Dudes schools consumed 46% more
      F/V than control schools, with no difference between prize and praise schools. At
      6-month follow-up, only prize schools consumed more F/V than control schools
      (0.12 cups more per child, 42.9% difference). CONCLUSIONS: Social praise proved
      an inadequate substitute for tangible prizes within the Food Dudes program.
      Program-related increases in F/V consumption decreased after the intervention,
      underscoring the need to develop low-cost, long-term interventions to maintain
      and make habitual consumption of recommended levels of F/V.

PMID- 26297599
TI  - Identification and molecular characterization of dorsal and dorsal-like genes in
      the cyclopoid copepod Paracyclopina nana.
AB  - To date, knowledge of the immune system in aquatic invertebrates has been
      reported in only a few model organisms, even though all metazoans have an innate
      immune system. In particular, information on the copepod's immunity and the
      potential role of key genes in the innate immune systems is still unclear. In
      this study, we identified dorsal and dorsal-like genes in the cyclopoid copepod
      Paracyclopina nana. In silico analyses for identifying conserved domains and
      phylogenetic relationships supported their gene annotations. The transcriptional
      levels of both genes were slightly increased from the nauplius to copepodid
      stages, suggesting that these genes are putatively involved in copepodid
      development of P. nana. To examine the involvement of both genes in the innate
      immune response and under stressful conditions, the copepods were exposed to
      lipopolysaccharide (LPS), different culture densities, salinities, and
      temperatures. LPS significantly upregulated mRNA expressions of dorsal and dorsal
      like genes, suggesting that both genes are transcriptionally sensitive in
      response to immune modulators. Exposure to unfavorable culture conditions also
      increased mRNA levels of dorsal and dorsal-like genes. These findings suggest
      that transcriptional regulation of the dorsal and dorsal-like genes would be
      associated with environmental changes in P. nana. 

PMID- 26297600
TI  - An embryonic transcriptome of the pulmonate snail Radix balthica.
AB  - The pond snail, Radix balthica (Linnaeus 1758), is an emerging model species
      within ecological developmental biology. While its development has been
      characterised in detail, genomic resources for embryonic stages are lacking. We
      applied Illumina MiSeq RNA-seq to RNA isolated from pools of embryos at two
      points during development. Embryos were cultured in either the presence or
      absence of predator kariomones to increase the diversity of the transcripts
      assembled. Sequencing produced 47.2M paired-end reads, assembled into 54,360
      contigs of which 73% were successfully annotated. This transcriptome provides an
      invaluable resource to build a mechanistic understanding of developmental
      plasticity. 

PMID- 26297601
TI  - Low-level repeated exposure to diazinon and chlorpyrifos decrease anxiety-like
      behaviour in adult male rats as assessed by marble burying behaviour.
AB  - Occupational exposure to organophosphate (OPs) pesticides is reported to increase
      in the risk of developing anxiety and depression. Preclinical studies using OP
      levels, which inhibit acetylcholinesterase activity, support the clinical
      observations, but little is known of the effects of exposure below this
      threshold. We examined the effects of low level OP exposure on behaviours and
      neurochemistry associated with affective disorders. Adult rats were administered
      either diazinon (1 mg/kg i.p.) which is present in sheep dip and flea collars,
      chlorpyrifos (1 mg/kg i.p.) which is present in crop sprays, or vehicle for 5
      days. OP exposure did not affect acetylcholinesterase activity (blood,
      cerebellum, caudate putamen, hippocampus, prefrontal cortex), anhedonia-like
      behaviour (sucrose preference), working memory (novel object recognition),
      locomotor activity or anxiety-like behaviour in the open field arena. In contrast
      OP exposure attenuated marble burying behaviour, an ethological measure of
      anxiety. The diazinon-induced reduction in marble burying persisted after
      exposure cessation. In comparison to vehicle, dopamine levels were lowered by
      chlorpyrifos, but not diazinon. 5-HT levels and turnover were unaffected by OP
      exposure. However, 5-HT transporter expression was reduced by diazinon suggesting
      subtle changes in 5-HT transmission. These data indicate exposure to occupational
      and domestic OPs, below the threshold to inhibit acetylcholinesterase, can subtly
      alter behaviour and neurochemistry.

PMID- 26297602
TI  - Chemical and Mineralogical Analysis of Ureteral Stent Encrustation and Associated
      Risk Factors.
AB  - OBJECTIVE: To assess the burden and chemical and mineralogical composition of
      stent coating at both stent ends, with evaluation of associated risk factors.
      MATERIALS AND METHODS: A total of 40 consecutive patients submitted to ureteral
      stent removal were considered. Stents were previously positioned for both
      urolithiasis and during the management of other urologic diseases and/or
      procedures. Mean indwelling time was 59.2 +/- 7.5 days. ANALYTICAL PROCEDURES:
      Encrustations were submitted to chemical-mineralogical analysis as well as to
      their quantification. Quantification was achieved by measuring the weight of
      stent fragments before and after oxidative acid treatment to dissolve the
      deposited (both organic and inorganic) material. The analytical solution obtained
      by acid attack was used to acquire information on calcium and magnesium content
      with atomic-absorption spectroscopy. X-ray diffraction was used to determine the
      mineralogy of encrustations for a group of stent samples characterized by
      relatively high amounts of deposited material. RESULTS: The composition of
      encrustations at the proximal coil reflected the composition of stones in
      patients with urolithiasis. Whewellite was the more common encrustant. In a
      regression model, the variable mostly related to the burden of proximal
      encrustation was urolithiasis (P = .04), especially in frequent stone formers. At
      the distal coil, higher degrees of encrustation were related to urinary tract
      infection (P = .012) and patient's aging (P = .05), thus suggesting a possible
      association with a bladder outlet dysfunction. CONCLUSION: The present study
      highlighted some variables related to stent encrustation and seems to be the
      first one analyzing separately the two coils. Our outcomes suggest that the so
      obtained risk factors have to be considered when positioning a ureteral stent.

PMID- 26297603
TI  - Total Anatomical Reconstruction During Robot-assisted Radical Prostatectomy:
      Implications on Early Recovery of Urinary Continence.
AB  - BACKGROUND: The introduction of robotics revolutionized prostate cancer surgery
      because the magnified three-dimensional vision system and wristed instruments
      allow microsurgery to be performed. The advantages of robotic surgery could lead
      to improved continence outcomes in terms of early recovery compared with the
      traditional surgical methods. OBJECTIVE: To describe the total anatomical
      reconstruction (TAR) technique during robot-assisted radical prostatectomy
      (RARP). PRIMARY ENDPOINT: evaluation of the continence rate at different time
      points. Secondary endpoint: evaluation of urine leakage and anastomosis stenosis
      rates related to the technique. DESIGN, SETTING, AND PARTICIPANTS: June, 2013 to
      November, 2014; prospective consecutive series of patients with localized
      prostate cancer (cT1-3, cN0, cM0). SURGICAL PROCEDURE: RARP with TAR was
      performed in all cases. Lymph node dissection was performed if the risk of lymph
      nodal metastasis was over 5%, according to the Briganti updated nomogram.
      MEASUREMENTS: Preoperative, intraoperative, postoperative, and pathological
      variables were analyzed. Enrolled patients were arbitrarily divided into three
      groups according to a time criterion. The relationships between the learning
      curve and the trend of the above-mentioned variables were analyzed using LOESS
      analysis. Continence was rigorously analyzed preoperatively and at 24h, 1 wk, 4
      wk, 12 wk, and 24 wk after catheter removal. RESULTS AND LIMITATIONS: In total,
      252 patients were analyzed. The continence rates immediately after catheter
      removal and at 1 wk, 4 wk, 12 wk, and 24 wk after RARP were 71.8%, 77.8%, 89.3%,
      94.4%, and 98.0%, respectively. Multivariate analysis revealed that the nerve
      sparing technique, D'Amico risk groups, lymph node dissection, and prostate
      volume were involved in the early recovery of urinary continence. One ileal
      perforation requiring reoperation was recorded. The transfusion rate was 0.8%.
      Thirty-one (12.3%) postoperative complications were recorded up to 6 mo after
      surgery. Among these, eight acute urinary retentions (3.2%) and three urine
      leakages (1.2%) were recorded. There was a lack of randomization and comparison
      with other techniques. Both anatomical dissection of the prostatic apex and TAR
      were used. The results may not be generalized to low-volume centers. CONCLUSIONS:
      The TAR technique showed promising results in the early recovery of urinary
      continence, as well as watertight anastomosis and a low rate of urine leakage.
      The oncologic results were not affected. Comparative studies are needed to
      support the quality of reported results. PATIENT SUMMARY: On the basis of our
      findings, it seems that the risk of urinary incontinence following radical
      prostatectomy can be lowered via meticulous anatomical reconstruction using a
      robotic system. Comparative studies are required to support the reported results.

PMID- 26297604
TI  - Guidelines on Testicular Cancer: 2015 Update.
AB  - CONTEXT: This is an update of the previous European Association of Urology testis
      cancer guidelines published in 2011, which included major changes in the
      diagnosis and treatment of germ cell tumours. OBJECTIVE: To summarise latest
      developments in the treatment of this rare disease. Recommendations have been
      agreed within a multidisciplinary working group consisting of urologists, medical
      oncologists, and radiation oncologists. EVIDENCE ACQUISITION: A semi-structured
      literature search up to February 2015 was performed to update the
      recommendations. In addition, this document was subjected to double-blind peer
      review before publication. EVIDENCE SYNTHESIS: This publication focuses on the
      most important changes in treatment recommendations for clinical stage I disease
      and the updated recommendations for follow-up. CONCLUSIONS: Most changes in the
      recommendations will lead to an overall reduction in treatment burden for
      patients with germ cell tumours. In advanced stages, treatment intensification is
      clearly defined to further improve overall survival rates. PATIENT SUMMARY: This
      is an update of a previously published version of the European Association of
      Urology guidelines for testis cancer, and includes new recommendations for
      clinical stage I disease and revision of the follow-up recommendations. Patients
      should be fully informed of all the treatment options available to them.

PMID- 26297605
TI  - Is Robot-assisted Cystectomy Better than Open?--Nearing an Answer after a Decade
      of Use.

PMID- 26297606
TI  - Questioning the significance of the non-identity problem in applied ethics: a
      reply to Tony Hope.
AB  - In this paper I reply to Tony Hope's response to my non-identity paper, aiming to
      clarify the nature of my objections, and also to address, briefly, Hope's
      suggestion that the implications of my view are that any book written for a lay
      audience ought to seek to present a 'balanced overview'. Essentially, I suggest
      that there may be a pro tanto consideration in favour of such an approach, but
      this would only be one consideration, to be weighed against competing
      considerations. 

PMID- 26297607
TI  - Borrelia-induced cytokine production is mediated by spleen tyrosine kinase (Syk)
      but is Dectin-1 and Dectin-2 independent.
AB  - Although it is known that Borrelia species express sugar-like structures on their
      outer surface, not much is known about the role of these structures in immune
      recognition by host cells. Fungi, like Candida albicans, are mainly recognized by
      C-type lectin receptors, in specific Dectin-1 and Dectin-2. In this study we
      assessed the role of Dectin-1 and Dectin-2 in the recognition process of Borrelia
      spirochetes. Using specific inhibitors against these receptors on human cells did
      not influenced cytokine production. Individuals carrying a SNP leading to an
      early stop codon in the DECTIN-1 gene also did not lead to differential induction
      of Borrelia-dependent cytokines. After injection of live Borrelia into knee
      joints of Dectin-2 deficient mice a trend towards lower inflammation was
      observed. Inhibition of Syk in human cells resulted in lower cytokine production
      after Borrelia stimulation. In conclusion, Dectin-1 and Dectin-2 seem not to play
      a major role in Borrelia recognition or Borrelia-induced inflammation. However,
      Syk seems to be involved in Borrelia-induced cytokine production. 

PMID- 26297608
TI  - Potential International Approaches to Ownership/Control of Human Genetic
      Resources.
AB  - In its governance activities for genetic resources, the international community
      has adopted various approaches to their ownership, including: free access; common
      heritage of mankind; intellectual property rights; and state sovereign rights.
      They have also created systems which combine elements of these approaches. While
      governance of plant and animal genetic resources is well-established
      internationally, there has not yet been a clear approach selected for human
      genetic resources. Based on assessment of the goals which international
      governance of human genetic resources ought to serve, and the implications for
      how they will be accessed and utilised, it is argued that common heritage of
      mankind will be the most appropriate approach to adopt to their
      ownership/control. It does this with the aim of stimulating discussion in this
      area and providing a starting point for deeper consideration of how a common
      heritage of mankind, or similar, regime for human genetic resources would
      function and be implemented. 

PMID- 26297610
TI  - Beclin 1 is dispensable for chromosome congression and proper outer kinetochore
      assembly.

PMID- 26297611
TI  - Response to Luca L Fava and colleagues.

PMID- 26297612
TI  - Oxidation-Responsive Polymer-Drug Conjugates with a Phenylboronic Ester Linker.
AB  - Polymer-drug conjugates have attracted great interest as one category of various
      promising nanomedicines due to the advantages of high drug-loading capacity,
      negligible burst release, and improved pharmacokinetics as compared with the
      small molecular weight drugs or the polymeric delivery systems with physically
      encapsulated drugs. Herein, a new type of oxidation-responsive polymer-drug
      conjugates composed of a poly(ethylene glycol) (PEG) block and a hydrophobic
      polyacrylate block to which Naproxen is attached through a phenylboronic ester
      linker is reported. The amphiphilic block copolymers are synthesized through the
      reversible addition-fragmentation chain transfer polymerization of the Naproxen
      containing acrylic monomer using a PEG chain transfer agent. In neutral aqueous
      buffer, the conjugates formed nanoparticles with diameters of ~150-300 nm
      depending on the length of the hydrophobic segment. The dynamic covalent bond of
      the phenylboronic ester is stabilized due to the hydrophobic microenvironment
      inside the nanoparticles. Upon exposure to H2 O2 , the phenylboronic ester is
      oxidized rapidly into the phenol derivative which underwent a 1,6-elimination
      reaction, releasing the intact Naproxen. The rate of drug release is influenced
      by the concentration of H2 O2 and the hydrophobic block length. This type of
      oxidation-responsive polymer-drug conjugate is feasible for other drugs
      containing hydroxyl group or amino group. 

PMID- 26297609
TI  - Ins and outs of GPCR signaling in primary cilia.
AB  - Primary cilia are specialized microtubule-based signaling organelles that convey
      extracellular signals into a cellular response in most vertebrate cell types. The
      physiological significance of primary cilia is underscored by the fact that
      defects in assembly or function of these organelles lead to a range of severe
      diseases and developmental disorders. In most cell types of the human body,
      signaling by primary cilia involves different G protein-coupled receptors
      (GPCRs), which transmit specific signals to the cell through G proteins to
      regulate diverse cellular and physiological events. Here, we provide an overview
      of GPCR signaling in primary cilia, with main focus on the rhodopsin-like (class
      A) and the smoothened/frizzled (class F) GPCRs. We describe how such receptors
      dynamically traffic into and out of the ciliary compartment and how they interact
      with other classes of ciliary GPCRs, such as class B receptors, to control
      ciliary function and various physiological and behavioral processes. Finally, we
      discuss future avenues for developing GPCR-targeted drug strategies for the
      treatment of ciliopathies. 

PMID- 26297613
TI  - Refractive index degeneration in older lenses: A potential functional correlate
      to structural changes that underlie cataract formation.
AB  - A major structure/function relationship in the eye lens is that between the
      constituent proteins, the crystallins and the optical property of refractive
      index. Structural breakdown that leads to cataract has been investigated in a
      number of studies; the concomitant changes in the optics, namely increases in
      light attenuation have also been well documented. Specific changes in the
      refractive index gradient that cause such attenuation, however, are not well
      studied because previous methods of measuring refractive index require
      transparent samples. The X-ray Talbot interferometric method using synchrotron
      radiation allows for measurement of fine changes in refractive index through
      lenses with opacities. The findings of this study on older human lenses show
      disruptions to the refractive index gradient and in the refractive index
      contours. These disruptions are linked to location in the lens and occur in polar
      regions, along or close to the equatorial plane or in lamellar-like formations.
      The disruptions that are seen in the polar regions manifest branching formations
      that alter with progression through the lens with some similarity to lens
      sutures. This study shows how the refractive index gradient, which is needed to
      maintain image quality of the eye, may be disturbed and that this can occur in a
      number of distinct ways. These findings offer insight into functional changes to
      a major optical parameter in older lenses. Further studies are needed to elicit
      how these may be related to structural degenerations reported in the literature. 

PMID- 26297614
TI  - Adenosine A3 receptor activation is neuroprotective against retinal
      neurodegeneration.
AB  - Death of retinal neural cells, namely retinal ganglion cells (RGCs), is a
      characteristic of several retinal neurodegenerative diseases. Although the role
      of adenosine A3 receptor (A3R) in neuroprotection is controversial, A3R
      activation has been reported to afford protection against several brain insults,
      with few studies in the retina. In vitro models (retinal neural and organotypic
      cultures) and animal models [ischemia-reperfusion (I-R) and partial optic nerve
      transection (pONT)] were used to study the neuroprotective properties of A3R
      activation against retinal neurodegeneration. The A3R selective agonist (2-Cl-IB
      MECA, 1 MUM) prevented apoptosis (TUNEL(+)-cells) induced by kainate and
      cyclothiazide (KA + CTZ) in retinal neural cultures (86.5 +/- 7.4 and 37.2 +/-
      6.1 TUNEL(+)-cells/field, in KA + CTZ and KA + CTZ + 2-Cl-IB-MECA, respectively).
      In retinal organotypic cultures, 2-Cl-IB-MECA attenuated NMDA-induced cell death,
      assessed by TUNEL (17.3 +/- 2.3 and 8.3 +/- 1.2 TUNEL(+)-cells/mm(2) in NMDA and
      NMDA+2-Cl-IB-MECA, respectively) and PI incorporation (ratio DIV4/DIV2 3.3 +/-
      0.3 and 1.3 +/- 0.1 in NMDA and NMDA+2-Cl-IB-MECA, respectively) assays.
      Intravitreal 2-Cl-IB-MECA administration afforded protection against I-R injury
      decreasing the number of TUNEL(+) cells by 72%, and increased RGC survival by
      57%. Also, intravitreal administration of 2-Cl-IB-MECA inhibited apoptosis (from
      449.4 +/- 37.8 to 207.6 +/- 48.9 annexin-V(+)-cells) and RGC loss (from 1.2 +/-
      0.6 to 8.1 +/- 1.7 cells/mm) induced by pONT. This study demonstrates that 2-Cl
      IB-MECA is neuroprotective to the retina, both in vitro and in vivo. Activation
      of A3R may have great potential in the management of retinal neurodegenerative
      diseases characterized by RGC death, as glaucoma and diabetic retinopathy, and
      ischemic diseases. 

PMID- 26297616
TI  - Lactobacillus casei stimulates phase-II detoxification system and rescues
      malathion-induced physiological impairments in Caenorhabditis elegans.
AB  - Malathion, an organophosphorus insecticide, is renowned for its inhibitory action
      on acetylcholinesterase (AChE) enzyme that eventually leads to widespread
      disturbance in the normal physiological and behavioral activities of any
      organism. Lactic acid bacteria (LAB) are still an underexploited and
      inexhaustible source of significant pharmaceutical thrust. In the present study,
      Caenorhabditis elegans was employed to identify and characterize the indigenous
      LAB isolated from different traditional food against malathion-induced toxicity.
      The results demonstrated that malathion at its LD50 concentration decreased
      various C. elegans physiological parameters such as survival, feeding, and
      locomotion. Among the screened isolates, L. casei exhibited an excellent
      protective efficacy against malathion-induced toxicity by increasing the level of
      AChE and thereby rescued all physiological parameters of C. elegans. In addition,
      short-term exposure and food choice assay divulged that L. casei could serve as a
      better food to protect C. elegans from noxious environment. The expression
      analysis unveiled that L. casei gavage upregulated the phase-II detoxification
      enzymes coding genes metallothioneins (mtl-1 and mtl-2) and glutathione-S
      transferase (gst-8) and thereby eliminated malathion from the host system.
      Furthermore, the upregulation of ace-3 along with down-regulation of cyp35a in
      the nematodes supplemented with L. casei could be attributed to attenuate the
      malathion-induced physiological defects in C. elegans. Thus, the present study
      reports that an indigenous LAB-L. casei could serve as a promising protective
      agent against the harmful effects of pesticide. 

PMID- 26297615
TI  - Beneficial effects of fenofibric acid on overexpression of extracellular matrix
      components, COX-2, and impairment of endothelial permeability associated with
      diabetic retinopathy.
AB  - In the Fenofibric Acid (FA) Intervention and Event Lowering in Diabetes (FIELD)
      study, FA, a lipid-lowering drug, has been shown to significantly reduce macular
      edema in diabetic patients. In the present study, we investigated whether FA
      reduces vascular permeability by inhibiting cyclooxygenase-2 (COX-2), a critical
      mediator of inflammation, and reducing overexpression of fibronectin (FN) and
      collagen IV (Coll IV), two basement membrane (BM) components upregulated in
      diabetic retinopathy. Rat retinal endothelial cells (RRECs) were grown in normal
      (N:5 mM glucose) or high glucose (HG:30 mM glucose) medium with or without FA for
      7 days. Total protein isolated from these cells was assessed for FN, Coll IV, COX
      2, and zonula occludens-1 (ZO-1), a tight junction protein, using Western blot
      analysis. In addition, the distribution and localization of ZO-1 was determined
      by immunofluorescence microscopy, and cell monolayer permeability was studied by
      in vitro permeability (IVP) assay. RRECs grown in HG medium showed significant
      increase in FN, Coll IV, and COX-2 expression (179%, 144%, 139% of N
      respectively), and a decrease in ZO-1 expression (48% of N) compared to those of
      N cells. Cells grown in HG medium supplemented with FA significantly reduced FN,
      Coll IV, and COX-2 expression by 47%, 32%, and 34% respectively, with concomitant
      increase in ZO-1 expression by 42%. In parallel studies, IVP assays showed a
      significant increase (139% of N) in cell monolayer permeability in RRECs grown in
      HG medium, which was significantly reduced with FA treatment. Additionally,
      immunostaining results indicated FA prevents HG-induced downregulation of ZO-1.
      The findings indicate that the beneficial effect of FA in reducing excess
      permeability is mediated, at least in part, by downregulating abnormal
      overexpression of BM components and inflammatory factors and preventing
      compromised tight junctions associated with diabetic retinopathy. 

PMID- 26297617
TI  - The Lifestyle Engagement Activity Program (LEAP): Implementing Social and
      Recreational Activity into Case-Managed Home Care.
AB  - OBJECTIVES: The Lifestyle Engagement Activity Program (LEAP) incorporates social
      support and recreational activities into case-managed home care. This study's aim
      was to evaluate the effect of LEAP on engagement, mood, and behavior of home care
      clients, and on case managers and care workers. DESIGN: Quasi-experimental.
      SETTING: Five Australian aged home care providers, including 2 specializing in
      care for ethnic minorities. PARTICIPANTS: Clients (n = 189) from 5 home care
      providers participated. INTERVENTION: The 12-month program had 3 components: (1)
      engaging support of management and staff; (2) a champion to drive practice
      change; (3) staff training. Case managers were trained to set meaningful social
      and/or recreational goals during care planning. Care workers were trained in good
      communication, to promote client independence and choice, and in techniques such
      as Montessori activities, reminiscence, music, physical activity, and humor.
      MEASUREMENTS: Data were collected 6 months before program commencement, at
      baseline, and 6 and 12 months. The Homecare Measure of Engagement Staff report
      and Client-Family interview were primary outcomes. Secondary outcomes were the
      Cohen-Mansfield Agitation Inventory; apathy, dysphoria, and agitation subscales
      of the Neuropsychiatric Inventory-Clinician Rating; the geriatric depression
      scale; UCLA loneliness scale; and home care satisfaction scale. Staff provided
      information on confidence in engaging clients and the Utrecht Work Engagement
      Scale. RESULTS: Twelve months after program commencement, clients showed a
      significant increase in self- or family-reported client engagement (b = 5.39,
      t[113.09] = 3.93, P < .000); and a significant decrease in apathy (b = -0.23,
      t(117.00) = -2.03, P = .045), dysphoria (b = -0.25, t(124.36) = -2.25, P = .026),
      and agitation (b = -0.97, t(98.15) = -3.32, P = .001) on the Neuropsychiatric
      Inventory-Clinician. Case managers and care workers both reported significant
      increases in their confidence to socially and recreationally engage clients (b =
      0.52, t(21.33) = 2.80, P = .011, b = 0.29, t(198.69) = 2.58, P = .011,
      respectively). There were no significant changes in care worker-rated client
      engagement or client or family self-complete measures of depression or loneliness
      (P > .05). Client and family self-rated apathy increased over 12 months (b =
      0.04, t(43.36) = 3.06, P = .004; b = 3.63, t(34.70) = 2.20, P = .035)
      CONCLUSIONS: LEAP demonstrated that home care providers can incorporate social
      and recreational care into usual practice for older clients, and that this
      benefits clients' engagement, dysphoria, and agitation.

PMID- 26297618
TI  - Palliative Care in People With Young-Onset Dementia (YOD): An Undiscovered Area!

PMID- 26297619
TI  - Angiotensin-Converting Enzyme Inhibitor in Tube-Fed Patients With Stroke History.

PMID- 26297620
TI  - Selecting Patients for Rehabilitation.

PMID- 26297621
TI  - Geriatric Rehabilitation and Discharge Location After Hip Fracture in Relation to
      the Risks of Death and Readmission.
AB  - OBJECTIVES: To investigate the effects of geriatric rehabilitation on short-term
      risk of death and readmission after a hip fracture were investigated in a
      nationwide cohort. In addition, the association of discharge location (nursing
      home or patient's home) with the short-term risk of death was assessed. DESIGN,
      SETTING, AND PARTICIPANTS: The cohort consisted of 89,301 individuals at least 50
      years of age, with a first hip fracture registered in the Swedish quality
      register RIKSHOFT, the years 2004-2012. MEASURES: Short-term risk of death and
      readmission to hospital after discharge was compared at 8 hospitals, where most
      patients received inpatient care in geriatric wards, and those treated at 71
      regular hospitals. RESULTS: The risks of death within 30 days of admission were
      7.1% in patients admitted to geriatric ward hospitals and 7.4% in those treated
      at regular hospitals (multivariable-adjusted hazard ratio [HR] 0.91, 95% CI 0.85
      0.97), whereas the odds of readmission within 30 days of discharge were 8.7% and
      9.8%, respectively (multivariable-adjusted odds ratio 0.86, 95% CI 0.81-0.91).
      The risk of death was influenced by discharge location and inpatient length of
      stay (LOS). Thus, for patients discharged to short-term nursing homes with a LOS
      of at most 10 days, each additional day of LOS reduction increased the risk of
      death within 30 days of discharge by 13% (HR 1.13, 95% CI 1.08-1.18). This
      association was reduced in patients discharged to permanent nursing homes (HR
      1.04, 95% CI 1.02-1.07), and not significant in those discharged to their own
      home (OR 1.00, 95% CI 0.91-1.10). CONCLUSION: The risks of death and readmission
      were lower in patients with hip fracture who received care in hospitals with
      geriatric wards. The risk of death after discharge increased with shorter LOS,
      especially in patients discharged to short-term nursing homes.

PMID- 26297622
TI  - Expression of nerve growth factor and its receptor, tyrosine kinase receptor A,
      in rooster testes.
AB  - Nerve growth factor (NGF), which is required for the survival and differentiation
      of the nervous system, is also thought to play an important role in the
      development of mammalian reproductive tissues. To explore the function of NGF in
      the male reproductive system of non-mammalian animals, we determined the presence
      of NGF and its receptor, tyrosine kinase receptor A (TrkA), in rooster testes and
      investigated the regulation of NGF and TrkA expression by follicle-stimulating
      hormone (FSH). The mRNA and protein levels of NGF and TrkA in 6-week-old rooster
      testes were lower than those in 12-, 16- or 20-week age groups; levels were
      highest in the 16-week group. Immunohistochemistry showed that NGF and TrkA were
      both detected in spermatogonia, spermatocytes and spermatids. NGF
      immunoreactivity was observed in Leydig cells and strong TrkA signals were
      present in Sertoli cells. Meanwhile, FSH increased TrkA transcript levels in
      rooster testes in a dose-dependent manner. We present novel evidence for the
      developmental and FSH-regulated expression of the NGF/TrkA system, and our
      findings suggest that the NGF/TrkA system may play a prominent role in chicken
      spermatogenesis. 

PMID- 26297623
TI  - Impact of thermal stress on the efficiency of ovulation synchronization protocols
      in Holstein cows.
AB  - The objective of this study was to evaluate the impact of thermal stress on the
      efficiency of three different protocols to synchronize time of ovulation in
      purebred Holstein cows under subtropical Egyptian conditions. The influence of
      temperature humidity index (THI) on the conception, pregnancy, embryonic loss and
      early abortion rates were investigated. Conception and pregnancy rates using the
      CIDRsynch and Presynch (37.5% and 33.9%; 29.5 and 29. 6%, respectively) were
      significantly greater than that for cows expressing spontaneous estrus (SE) and
      with use of the Ovsynch (28.5% and 24.3%; 21.6% and 24.6%, respectively)
      treatment regimen. Conception and pregnancy rates using the Ovsynch protocol were
      significantly decreased from 31.6% and 26.3% at the lesser THI to 11.5% and 9.9%,
      respectively than at the greater THI [crude odds ratio (COR) = 0.28 and 0.32; P =
      0.001 and 0.004, respectively]. However, conception (P/AI at 28 days) and
      pregnancy (P/AI at 75 days) rates using the Presynch protocol were significantly
      reduced at either the lesser or greater THI (COR = 0.47 and 0.42; 0.48 and 0.34,
      respectively). Embryonic loss rate with the Presynch group was significantly
      increased from 11.5% at the lesser THI to 22.2% at the greater THI (COR = 2.28; P
      = 0.039). In contrast, conception, pregnancy and embryonic loss rates did not
      differ significantly (P > 0.05) with the CIDRsynch protocol at the different THI.
      Results from the present study indicate that use of the CIDRsynch protocol may
      provide consistent and satisfactory conception and pregnancy rates in Holstein
      cows under subtropical environmental conditions.

PMID- 26297624
TI  - Validity of the Parenting Stress Index Short Form in a Sample of At-Risk Mothers.
AB  - BACKGROUND: The Parenting Stress Index Short Form (PSI-SF) is a widely used
      instrument in scientific literature to evaluate the levels of stress a parent
      feels when facing parenting-related tasks. Despite the potential usefulness of
      the PSI-SF with at-risk families, no validation studies have been carried out on
      this population in Spain. OBJECTIVES: The main objective of this study is to
      report evidences of the reliability and validity of PSI-SF with a sample of at
      risk mothers. Specifically, (1) to examine the discriminative capacity of PSI-SF
      to differentiate between a community sample and another sample composed of
      families with various levels of risk and (2) to analyze the relationships with
      general health indicators and parental sense of competence. RESULTS: Analyses
      reported in this article show satisfactory results regarding appropriate internal
      consistency coefficients for the scale. With respect to the evidences of
      validity, results reported here suggest that the total PSI-SF score, but not the
      two subscales, could be useful to differentiate between different groups of
      mothers with different levels of risk. The Childrearing stress subscale was
      associated with a poorer perception as a mother as well as with an external locus
      of control, and the Personal distress subscale was related to all the general
      health indicators, explaining a high percentage of variance. CONCLUSION: The
      results reported show that the total score or the subscales should be used in a
      differentiated way according to the professional's objectives. Hence, PSI-SF may
      be a useful instrument for researchers and practitioners who work with at-risk
      families.

PMID- 26297625
TI  - Numerosity processing is context driven even in the subitizing range: An fMRI
      study.
AB  - Numerical judgments are involved in almost every aspect of our daily life. They
      are carried out so efficiently that they are often considered to be automatic and
      innate. However, numerosity of non-symbolic stimuli is highly correlated with its
      continuous properties (e.g., density, area), and so it is hard to determine
      whether numerosity and continuous properties rely on the same mechanism. Here we
      examined the behavioral and neuronal mechanisms underlying such judgments. We
      scanned subjects' hemodynamic responses to a numerosity comparison task and to a
      surface area comparison task. In these tasks, numerical and continuous magnitudes
      could be either congruent or incongruent. Behaviorally, an interaction between
      the order of the tasks and the relevant dimension modulated the congruency
      effects. Continuous magnitudes always interfered with numerosity comparison.
      Numerosity, on the other hand, interfered with the surface area comparison only
      when participants began with the numerosity task. Hemodynamic activity showed
      that context (induced by task order) determined the neuronal pathways in which
      the dimensions were processed. Starting with the numerosity task led to enhanced
      activity in the right hemisphere, while starting with the continuous task led to
      enhanced left hemisphere activity. Continuous magnitudes processing relied on
      activation of the frontal eye field and the post-central gyrus. Processing of
      numerosities, on the other hand, relied on deactivation of these areas,
      suggesting active suppression of the continuous dimension. Accordingly, we
      suggest that numerosities, even in the subitizing range, are not always processed
      automatically; their processing depends on context and task demands. 

PMID- 26297626
TI  - Antigenic assessment of a recombinant human CD90 protein expressed in prokaryotic
      expression system.
AB  - Cluster of Differentiation 90 (CD90, Thy-1) has been proposed as one of the most
      important biomarkers in several cancer cells including cancer stem cells (CSCs).
      CD90 is considered as a potential normal stem cell and CSCs biomarker and also
      has been identified in lung cancer stem cells, hepatocellular carcinoma cells and
      high-grade gliomas. Using eukaryotic host systems involves complex procedures and
      frequently results in low protein yields. The expression of recombinant proteins
      in Escherichia coli is comparatively easier than eukaryotic host cells. The
      potential of large scale production of recombinant protein has made this system
      an economic production platform. In this study we expressed the extra-membrane
      domain of human CD90 (exCD90) antigen (Gln15-Cys130) in E. coli expression host
      cells. The epitope integrity of purified recombinant antigen was confirmed by
      antibody-antigen interaction using 5E10 anti-CD90 monoclonal antibody and binding
      study through ELISA and florescent staining of CD90(+) cells in a flow cytometry
      experiment. 

PMID- 26297627
TI  - More Than Telemonitoring: Health Provider Use and Nonuse of Life-Log Data in
      Irritable Bowel Syndrome and Weight Management.
AB  - BACKGROUND: The quantified self, self-monitoring or life-logging movement is a
      trend to incorporate technology into data acquisition on aspects of a person's
      daily life in terms of inputs (eg food consumed), states (eg mood), and
      performance (mental and physical). Consumer self-monitoring mobile phone apps
      have been widely studied and used to promote healthy behavior changes. Data
      collected through life-logging apps also have the potential to support clinical
      care. OBJECTIVE: We sought to develop an in-depth understanding of providers'
      facilitators and barriers to successfully integrating life-log data into their
      practices and creating better experiences. We specifically investigated three
      research questions: How do providers currently use patient-collected life-log
      data in clinical practice? What are provider concerns and needs with respect to
      this data? What are the constraints for providers to integrate this type of data
      into their workflows? METHODS: We interviewed 21 health care providers
      physicians, dietitians, a nurse practitioner, and a behavioral psychologist-who
      work with obese and irritable bowel syndrome patients. We transcribed and
      analyzed interviews according to thematic analysis and an affinity diagramming
      process. RESULTS: Providers reported using self-monitoring data to enhance
      provider-patient communication, develop personalized treatment plans, and to
      motivate and educate patients, in addition to using them as diagnostic and
      adherence tools. However, limitations associated with current systems and
      workflows create barriers to regular and effective review of this data. These
      barriers include a lack of time to review detailed records, questions about
      providers' expertise to review it, and skepticism about additional benefits
      offered by reviewing data. Current self-monitoring tools also often lack
      flexibility, standardized formats, and mechanisms to share data with providers.
      CONCLUSIONS: Variations in provider needs affect tracking and reviewing needs.
      Systems to support diagnosis might require better reliability and resolution,
      while systems to support interaction should support collaborative reflection and
      communication. Automatic synthesis of data logs could help providers focus on
      educational goals while communication of contextual information might help
      providers better understand patient values. We also discuss how current mobile
      apps and provider systems do, and do not, support these goals, and future design
      opportunities to realize the potential benefits of using life-logging tools in
      clinical care.

PMID- 26297628
TI  - Clinical presentation and long-term outcome of 144 patients with microscopic
      polyangiitis in a monocentric German cohort.
AB  - OBJECTIVE: To evaluate the clinical presentation and long-term outcome of a
      vasculitis centre cohort of patients with microscopic polyangiitis (MPA) with
      respect to organ manifestations, treatment, chronic damage and mortality.
      METHODS: We performed a retrospective chart review at our vasculitis referral
      centre. MPA patients admitted between 1991 and 2013 classified by a modified
      European Medicines Agency algorithm were diagnosed and treated according to a
      standardized interdisciplinary approach. RESULTS: Comprehensive data from
      standardized interdisciplinary workups was available for 144 patients (median
      follow-up 72 months). The overall standardized mortality ratio was 1.40 (95% CI
      0.91, 2.07; P = 0.13). We observed a higher mortality [hazard ratio (HR) 4.04
      (95% CI 1.21, 13.45), P = 0.02] in 17 patients with MPA-associated fibrosing
      interstitial lung disease (ILD) and 56 patients with peripheral nervous system
      involvement [HR 5.26 (95% CI 1.10, 25.14), P = 0.04] at disease onset. One
      hundred and fifteen patients (79.9%) responded to the initial treatment. Sixty
      one (42.3%) achieved complete remission and 54 (37.5%) achieved partial
      remission. Twenty (13.9%) showed a refractory disease course. CONCLUSION: MPA
      patients at our tertiary rheumatology referral centre seemed to have a less
      severe phenotype resulting in a less severe disease course and better outcome
      than reported in other cohorts. Fibrosing ILD was significantly associated with
      mortality in this cohort.

PMID- 26297629
TI  - Facing the fear of failure: An explorative qualitative study of client
      experiences in a mindfulness-based stress reduction program for university
      students with academic evaluation anxiety.
AB  - The aim of this qualitative study was to investigate the subjective experiences
      of 29 university students who participated in an 8-week mindfulness-based stress
      reduction (MBSR) program for academic evaluation anxiety. Participants who self
      referred to the Student Counseling Service underwent individual semi-structured
      interviews about how they experienced the personal relevance and practical
      usefulness of taking the MBSR program. Interviews were transcribed and analyzed
      through a team-based explorative-reflective thematic approach based on a
      hermeneutic-phenomenological epistemology. Five salient patterns of meaning
      (themes) were found: (1) finding an inner source of calm, (2) sharing a human
      struggle, (3) staying focused in learning situations, (4) moving from fear to
      curiosity in academic learning, and (5) feeling more self-acceptance when facing
      difficult situations. We contextualize these findings in relation to existing
      research, discuss our own process of reflexivity, highlight important limitations
      of this study, and suggest possible implications for future research. 

PMID- 26297630
TI  - Applicability of the Zwolle risk score for safe early discharge after primary
      percutaneous coronary intervention in ST-segment elevation myocardial infarction.
AB  - INTRODUCTION AND AIM: The optimal length of stay for patients with uncomplicated
      ST-segment elevation myocardial infarction (STEMI) treated with primary
      percutaneous coronary intervention (PPCI) is still undetermined. The Zwolle risk
      score (ZRS) is a simple tool designed to identify patients who can be safely
      discharged within 72 hours. The purpose of this study was to assess the
      applicability and performance of the ZRS in our population. METHODS: We studied
      276 consecutive patients (mean age 62 +/- 14 years, 75% male, 20% Killip class
      >1) admitted over a two-year period for STEMI and treated with PPCI. ZRS, length
      of stay, 30-day mortality and readmission were obtained for all patients. Low
      risk was defined as ZRS <= 3. RESULTS: The median ZRS was 3 (interquartile range
      [IQR] 1-4), with 171 patients (62%) being classified as low risk. Thirty-day
      mortality was 4.7% (13 patients). Compared to other patients, low-risk patients
      had shorter length of stay (median 5.0 [IQR 4-7] vs. 7.0 [5-13] days, p<0.001),
      and lower 30-day mortality (0 vs. 12.4%, p<0.001), yielding a negative predictive
      value of 100% (95% CI 97.0-100%) for the proposed cutoff. The ZRS showed
      excellent discriminative power (C-statistic: 0.937, 95% CI 0.906-0.968, p<0.001),
      and good calibration against the original cohort. CONCLUSIONS: The ZRS appears to
      perform well in identifying low-risk STEMI patients who could be safely
      discharged within 72 hours of admission. Using the ZRS in our population could
      result in a more rational use of in-patient resources.

PMID- 26297631
TI  - Introduction of percutaneous treatment for mitral regurgitation in Portugal.

PMID- 26297632
TI  - Creatine as a booster for human brain function. How might it work?
AB  - Creatine, a naturally occurring nitrogenous organic acid found in animal tissues,
      has been found to play key roles in the brain including buffering energy supply,
      improving mitochondrial efficiency, directly acting as an anti-oxidant and acting
      as a neuroprotectant. Much of the evidence for these roles has been established
      in vitro or in pre-clinical studies. Here, we examine the roles of creatine and
      explore the current status of translation of this research into use in humans and
      the clinic. Some further possibilities for use of creatine in humans are also
      discussed. 

PMID- 26297634
TI  - Prediction of root coverage for single recessions in anterior teeth: a 6-month
      study.
AB  - BACKGROUND: The aim of this study was to evaluate the predictive values of
      baseline inter-dental papilla height (IPH), loss of inter-dental papilla height
      (LPH), avascular exposed root surface area (AERSA) and inter-dental clinical
      attachment level (ICAL) measurements on complete root coverage (CRC) of single
      recession defects treated with coronally advanced flap and connective tissue
      graft technique (CAF+CTG). MATERIAL & METHODS: A total of 122 patients with one
      isolated gingival recession were enrolled. All recession defects without loss of
      ICAL (ID-CAL) (RT1) and with an amount of ID-CAL equal or smaller to the buccal
      attachment loss (RT2), located at upper and lower anterior teeth were treated
      with CAF+CTG. IPH, LPH, AERSA and ICAL parameters were analysed for possible
      correlation with CRC after 6 months. RESULTS: The CRC was 86.7% for RT1, 74.2%
      for RT2 groups. The ROC analyses revealed acceptable cut-off points for baseline
      AERSA, IPH and LPH for achieving CRC. The results of logistic regression analyses
      showed that having baseline AERSA>=19 mm(2) (OR:23.7), IPH lower <=1 mm (OR:97.3)
      and belonging to RT2 group (OR:15.0) were found to be independent risk factors
      related with not achieving final CRC. CONCLUSION: This study indicates that AERSA
      and IPH may be used to predict the final CRC outcomes in RT1 and RT2 defects
      treated with CAF+CTG.

PMID- 26297633
TI  - Bacterial antibiotic resistance studies using in vitro dynamic models: Population
      analysis vs. susceptibility testing as endpoints of mutant enrichment.
AB  - Emergence of bacterial antibiotic resistance is usually characterised either by
      population analysis or susceptibility testing. To compare these endpoints in
      their ability to demonstrate clear relationships with the ratio of 24-h area
      under the concentration-time curve (AUC24) to the minimum inhibitory
      concentration (MIC), enrichment of ciprofloxacin-resistant mutants of four
      clinical isolates of Pseudomonas aeruginosa was studied in an in vitro dynamic
      model that simulates mono-exponential pharmacokinetics of ciprofloxacin over a
      wide range of the AUC24/MIC ratios. Each organism was exposed to twice-daily
      ciprofloxacin for 3 days. Amplification of resistant mutants was monitored by
      plating on media with 2*, 4*, 8* and 16* MIC of ciprofloxacin. Population
      analysis data were expressed by the area under the bacterial mutant concentration
      time curve (AUBCM). Changes in P. aeruginosa susceptibility were examined by
      daily MIC determinations. To account for the different susceptibilities of P.
      aeruginosa strains, post-exposure MICs (MICfinal) were related to the MICs
      determined with the starting inoculum (MICinitial). For each organism, AUC24/MIC
      relationships both with AUBCM and MICfinal/MICinitial were bell-shaped, but the
      latter were more strain-specific than the former. Using combined data on all four
      isolates, AUBCM showed a better correlation than MICfinal/MICinitial (r(2)=0.75
      vs. r(2)=0.53). The shift of MICfinal/MICinitial relative to AUBCM vs. AUC24/MIC
      curves resulted in a weak correlation between AUBCM and MICfinal/MICinitial
      (r(2)=0.41). These data suggest that population analysis is preferable to
      susceptibility testing in bacterial resistance studies and that these endpoints
      should not be considered interchangeable. 

PMID- 26297635
TI  - Chlamydial conjunctivitis: prevalence and serovar distribution of Chlamydia
      trachomatis in adults.
AB  - The extragenital manifestation of Chlamydia trachomatis infection frequently
      results in non-specific conjunctivitis among sexually active adults. The aims of
      the present study were to determine the prevalence of C. trachomatis, to describe
      the distribution of serovars among patients with conjunctivitis and to
      characterize the relationship between the prevalence and patient demographics
      such as age and gender. A total of 245 conjunctival specimens were screened for
      C. trachomatis DNA targeting the plasmid gene. Serovar determination of the C.
      trachomatis-positive specimens was carried out by an omp1 PCR-based RFLP analysis
      method. Statistical analysis was done using a generalized linear model. C.
      trachomatis was detected in 53 cases (21.6 %) of adult conjunctivitis. Molecular
      genotyping differentiated seven distinct urogenital serovars, the most prevalent
      being serovar E (16/53), followed by F (15/53), D (6/53), K (6/53), G (4/53), H
      (4/53) and J (2/53). Statistical analysis showed higher C. trachomatis prevalence
      in the younger age groups, and this peaked at younger age in women than in men.
      The high prevalence of this pathogen found in ocular samples should alert
      ophthalmologists to focus on the role of C. trachomatis in adult conjunctivitis.
      The serovar distribution indicated that ocular chlamydial infections usually have
      a genital source. Nevertheless, conjunctivitis might be the only sign of this
      sexually transmitted infection. Further comparative genotyping of C. trachomatis
      in ocular and genital specimens might give more detailed epidemiological
      information about the aetiology of the disease.

PMID- 26297636
TI  - Inhibitory effect of GB-2a (I3-naringenin-II8-eriodictyol) on melanogenesis.
AB  - ETHNOPHARMACOLOGY RELEVANCE: GB-2a is a I3-naringenin-II8-eriodictyol compound
      isolated from Garcinia gardneriana (Planchon & Triana) Zappi, a plant used in
      folk medicine for the treatment of skin disorders. AIM OF STUDY: In the search
      for new depigmenting agents, this study was carried out to investigate the in
      vitro effects of GB-2a isolated from G. gardneriana (Planchon & Triana) Zappi in
      B16F10 melanoma cells. MATERIALS AND METHODS: The effects of GB-2a were evaluated
      through determination of melanin biosynthesis in B16F10 melanoma cells in
      comparison with the reference drug kojic acid (500uM). In parallel, the GB-2a
      effect was assessed in a cell viability assay. Mushroom tyrosinase activity
      assays were conducted to verify the effect of this enzyme. In order to ascertain
      the nature of enzyme inhibition on tyrosinase, kinetics analysis of the GB-2a was
      performed with L-tyrosine and L-3,4-dihydroxyphenylalanine (L-DOPA) substrates.
      RESULTS: The results showed that GB-2a biflavonoid significantly inhibited the
      melanin content, without reducing cell viability. GB-2a also showed a strong
      antityrosinase activity in the mushroom tyrosinase assay. GB-2a inhibited the
      tyrosinase activity, exerting a mixed inhibition. For the L-tyrosine substrate
      the inhibition was in non-competitive mode and for L-DOPA it was in uncompetitive
      mode. CONCLUSION: GB-2a biflavonoid promoted inhibition on tyrosinase activity
      and reduced melanin biosynthesis in B16F10 cells, which suggests great potential
      for medical and cosmetic uses as a depigmenting agent.

PMID- 26297637
TI  - Safety assessment of saponins extract in Dolichos falcatus Klein: Subchronic
      study in Sprague-Dawley rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Dolichos falcatus Klein (DF), a Chinese Dai
      ethnic medicine popularly known as "Tuoyeteng" in Yunnan province of China, has
      been widely used in China to treat fracture, rheumatoid arthritis and soft tissue
      injuries for a long time. Our previous study showed that saponins in DF (DFS)
      ameliorated the gouty arthritis induced by MSU crystals in vivo and in vitro. The
      present study was carried out to evaluate the no-observed-adverse-effect level
      (NOAEL) of DFS. MATERIALS AND METHODS: Sprague-Dawley rats (10/sex/group) were
      gavaged with DFS at dose level of 0, 50, 100 and 200 mg/kg body weight /day for
      90-days. RESULTS: DFS administration did not result in mortality or show
      treatment-related changes in clinical signs of toxicity, body weights gain or
      feed consumption. Similarly, in addition to slightly hemolytic anemia and
      gastrointestinal tract lesion in males of high-dose treatment group, no
      toxicologically significant treatment-related changes in hematological, clinical
      chemistry, urine analysis parameters, organ weights, and macroscopic and
      microscopic abnormalities were noted during the testing period. CONCLUSION: The
      results of subchronic toxicity study support the NOAEL for DFS as 200 mg/kg/d in
      females and as 100mg/kg/d in males. These results provide an important reference
      for further DFS-related clinical trials or new drug exploration.

PMID- 26297638
TI  - Inventory of U.S. 2012 dioxin emissions to atmosphere.
AB  - In 2006, the U.S. EPA published an inventory of dioxin emissions for the U.S.
      covering the period from 1987-2000. This paper is an updated inventory of all
      U.S. dioxin emissions to the atmosphere in the year 2012. The sources of
      emissions of polychlorinated dibenzodioxins (PCDDs) and polychlorinated
      dibenzofurans (PCDFs), collectively referred to in this paper as "dioxins", were
      separated into two classes: controlled industrial and open burning sources.
      Controlled source emissions decreased 95.5% from 14.0 kg TEQ in 1987 to 0.6 kg in
      2012. Open burning source emissions increased from 2.3 kg TEQ in 1987 to 2.9 kg
      in 2012. The 2012 dioxin emissions from 53 U.S. waste-to-energy (WTE) power
      plants were compiled on the basis of detailed data obtained from the two major
      U.S. WTE companies, representing 84% of the total MSW combusted (27.4 million
      metric tons). The dioxin emissions of all U.S. WTE plants in 2012 were 3.4 g TEQ
      and represented 0.54% of the controlled industrial dioxin emissions, and 0.09% of
      all dioxin emissions from controlled and open burning sources.

PMID- 26297640
TI  - Modifying the "Modified Schwartz Equation" for Lung Cancer Volume Estimates.

PMID- 26297641
TI  - Results of the 2015 Survey of the American Alliance of Academic Chief Residents
      in Radiology.
AB  - RATIONALE AND OBJECTIVES: The American Alliance of Academic Chief Residents in
      Radiology conducts an annual survey of chief residents in Diagnostic Radiology
      programs in North America. The survey serves as a resource for observing trends
      and disseminating ideas among radiology training programs. MATERIALS AND METHODS:
      An online survey was distributed to chief residents at 181 residency programs,
      with questions on a broad range of topics including resident benefits, program
      and call structure, American Board of Radiology Core exam preparation,
      fellowships, and the job market. RESULTS: A total of 193 individual responses
      were received from 120 programs, for a response rate of 66%. The responses were
      compared to data from prior years' surveys, principally from 2012 to 2014.
      CONCLUSIONS: Programs are shifting resident benefits spending toward Core exam
      preparation resources and away from lead aprons. In addition, 24-hour attending
      coverage continues to spread among programs, and the fraction of programs
      providing face-to-face postcall readouts continues to decline. Finally, although
      resident perception of the job market is now improving, residents feel that the
      job market continues to discourage medical students from entering radiology, a
      fact borne out by the 2015 match results. How the upcoming change to a direct
      interventional radiology residency will affect medical student interest is as yet
      uncertain.

PMID- 26297639
TI  - HIV-1 protease cleaves the serine-threonine kinases RIPK1 and RIPK2.
AB  - BACKGROUND: HIV-1 protease (PR) is essential for viral infectivity as it cleaves
      Gag and Gag-Pol polyprotein precursors during viral maturation. Recent evidence
      suggests that cellular proteins can also be cleaved by PR, perhaps representing
      an important viral strategy to counter host defense mechanisms. Receptor
      interacting protein kinase 1 (RIPK1) and RIPK2 belong to a family of
      serine/threonine kinases with conserved domain architecture and important
      functions in apoptosis, necrosis and innate immunity. RESULTS: We found that
      RIPK1 and RIPK2 but not other members of the RIP kinase family are cleaved by HIV
      1 PR. In RIPK1, we identified a putative PR cleavage site; a mutation at this
      site rendered RIPK1 resistant to PR cleavage. RIPK1 and RIPK2 were cleaved during
      HIV-1 infection of T cell lines or primary activated CD4(+) T cells. Interfering
      with the viral life cycle at different stages by the addition of specific
      inhibitors against RT, integrase, or PR, completely prevented RIPK1 and RIPK2
      cleavage. Cleavage of RIPK1 disrupted RIPK1/RIPK3 complex formation and RIPK1
      mediated induction of NF-kB. CONCLUSIONS: These findings indicate that RIPK1 and
      RIPK2 are targets of HIV-1 PR activity during infection, and their inactivation
      may contribute to modulation of cell death and host defense pathways by HIV-1.

PMID- 26297642
TI  - Evaluation of the potential therapeutic effects of a double-stranded RNA mimic
      complexed with polycations in an experimental mouse model of endometriosis.
AB  - OBJECTIVE: To assess the therapeutic potential of polyinosine-polycytidylic acid,
      a double-stranded RNA molecule with selective proapoptotic and antiangiogenic
      activity, complexed with polyethyleneimine (pIC(PEI)) in treating endometriosis.
      DESIGN: A heterologous mouse model of endometriosis was created by injecting
      human endometrial fragments into the peritoneum. Endometrial fragments were
      engineered to express the fluorescent protein mCherry as a reporter to monitor
      status over the course of the 4-week study. SETTING: University-affiliated
      infertility center. ANIMAL(S): Ovariectomized and hormone-replaced nude mice (n =
      30) injected with fluorescent-labeled human endometrial fragments at 4-6 weeks of
      age. INTERVENTION(S): Animals (n = 10 per group) were injected with vehicle
      (control), the anti-VEGF compound CBO-P11 (0.6 mg/kg), or pIC(PEI) (0.6 mg/kg)
      twice weekly over the course of 4 weeks. MAIN OUTCOME MEASURE(S): Variations in
      the size of endometriotic implants were estimated by quantifying the expression
      of mCherry throughout the course of the experiment. Neovascularization, cellular
      proliferation, and apoptosis were estimated by quantitative immunofluorescence
      detection of PECAM, alpha-SMA, Ki67, and TUNEL. RESULT(S): pIC(PEI) promoted a
      significant increase in apoptosis and a decrease in neovascularization in human
      fragments, but did not reduce the size of endometriotic implants. CONCLUSION(S):
      While pIC(PEI) treatment had significant antiangiogenic and pro-apoptotic effects
      in this setting, longer periods of exposure than the ones supported by our
      heterologous model and/or assays in homologous mouse models of endometriosis may
      be necessary to detect an effect of this compound on lesion size.

PMID- 26297643
TI  - Pregnancy-associated plasma protein A in human ovarian follicles and its
      association with intrafollicular hormone levels.
AB  - OBJECTIVE: To evaluate follicular fluid (FF) levels of pregnancy-associated
      plasma protein A (PAPP-A) in relation to levels of intrafollicular hormones.
      Furthermore, immunostaining of human follicles of varying diameters was studied
      for PAPP-A, antimullerian hormone (AMH), and aromatase, and the biological
      activity of PAPP-A in FF was evaluated. DESIGN: Laboratory investigation.
      SETTING: University hospital. PATIENT(S): A total of 43 women with a total of 80
      samples were obtained from three different size-groups of antral follicles
      collected before and after the LH surge. INTERVENTION(S): ELISA measurement of
      steroids, PAPP-A, and AMH, immunohistochemistry of PAPP-A, AMH, and aromatase on
      follicles of different diameter, and proteolytic activity of PAPP-A toward
      insulin-like growth factor (IGF)-binding protein 4 (IGFBP-4). MAIN OUTCOME
      MEASURE(S): Association between FF levels of PAPP-A and measured ovarian
      hormones, PAPP-A activity in FF, localization of PAPP-A, AMH, and aromatase in
      antral follicles. RESULT(S): A highly significant association between FF levels
      of PAPP-A and all measured hormones were obtained with positive associations
      toward E2 and P, whereas AMH, T, and A showed strong negative associations. PAPP
      A proteolytic activity toward IGFBP-4 was detected in human FF. PAPP-A
      immunostaining shifted from being primarily present in theca cells of small
      antral follicles to being expressed in granulosa cells (GCs) of preovulatory
      follicles. In contrast, AMH expression became reduced with increasing follicular
      diameter. Aromatase expression was highly specifically localized to GCs of
      preovulatory follicles. CONCLUSION(S): The results suggest that PAPP-A is
      specifically involved in the regulation of steroidogenesis in human antral
      follicles. Local regulation of IGF-II activity may represent a mechanism by which
      PAPP-A exerts this function and highlights the importance of IGF signaling during
      follicular development.

PMID- 26297644
TI  - Nuclear magnetic resonance metabolomic profiling of urine provides a noninvasive
      alternative to the identification of biomarkers associated with endometriosis.
AB  - OBJECTIVE: To investigate whether urine metabolomic profile can be used to
      identify biomarkers associated to endometriosis. DESIGN: Prospective study. For
      each subject, a urine sample was collected after overnight fasting and before
      surgery. SETTING: University medical center. PATIENT(S): The clinical cohort
      included 45 endometriosis patients, diagnosed at early (n = 6) and advanced (n =
      39) stages of the disease, and 36 healthy women. All women underwent diagnostic
      laparoscopy to visually confirm the presence or absence of endometriotic lesions.
      INTERVENTION(S): Metabolomic profiling of urine samples based on (1)H-nuclear
      magnetic resonance (NMR) spectroscopy in combination with statistical approaches.
      MAIN OUTCOME MEASURE(S): Comparative identification of metabolites present in
      urine from endometriosis patients and healthy women. RESULT(S): The urine
      metabolomic profile of endometriosis patients exhibited higher concentrations of
      N(1)-methyl-4-pyridone-5-carboxamide, guanidinosuccinate, creatinine, taurine,
      valine, and 2-hydroxyisovalerate and decreased concentrations of lysine compared
      with healthy women. Most of these metabolites are involved in inflammation and
      oxidative stress processes. These pathophysiologic events had been previously
      described to be present in ectopic endometrial proliferation foci. CONCLUSION(S):
      Overall, the results demonstrate the potential of (1)H-NMR-based metabolomics, a
      rapid and noninvasive approach, to identify metabolic changes associated to
      endometriosis in urine samples. This information could be useful to get a better
      understanding of the pathogenesis of endometriosis, thus providing support to the
      noninvasive diagnosis of this pathology.

PMID- 26297645
TI  - Exploring adhesion formation and prevention.

PMID- 26297646
TI  - Gonadotropin dose is negatively correlated with live birth rate: analysis of more
      than 650,000 assisted reproductive technology cycles.
AB  - OBJECTIVE: To evaluate the correlation between total gonadotropin dose and live
      birth rate. DESIGN: Retrospective analysis. SETTING: Not applicable. PATIENT(S):
      A total of 658,519 fresh autologous cycles of in vitro fertilization (IVF)
      reported to the Society for Assisted Reproductive Technology from 2004 to 2012.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Logistic regression models were
      fitted to live birth rates with the use of categorized values for total FSH dose
      and number of oocytes retrieved as the primary predictor variables. To reduce the
      effect of the most significant confounders that may lead physicians to prescribe
      higher doses of FSH, additional analyses were performed limited to good-prognosis
      patients (<35 years of age, body mass index <30 kg/m(2), and no diagnosis of
      diminished ovarian reserve, endometriosis, or ovulatory disorder) and including
      duration of gonadotropin treatment. RESULT(S): Live birth rate significantly
      decreased with increasing FSH dose, regardless of the number of oocytes
      retrieved. The statistically significant decrease in live birth rate with
      increasing FSH dose remained in patients with good prognosis, and regardless of
      female age, except for women aged >= 35 years with 1-5 oocytes retrieved.
      CONCLUSION(S): This analysis suggests that physicians may wish to avoid
      prescribing a high dose of FSH. However, the results of this study do not justify
      the use of minimal-stimulation or natural-cycle IVF.

PMID- 26297647
TI  - Live birth following in vitro maturation of oocytes retrieved from extracorporeal
      ovarian tissue aspiration and embryo cryopreservation for 5 years.
AB  - OBJECTIVE: To report a live birth after in vitro maturation (IVM) of oocytes
      retrieved from extracorporeal ovarian tissue aspiration in the setting of
      fertility preservation. DESIGN: Observational study. SETTING: Academic center.
      PATIENT(S): A 23-year-old woman. INTERVENTION(S): IVM from extracorporeal ovarian
      tissue aspiration. MAIN OUTCOME MEASURE(S): Live birth after IVM. RESULT(S): A 23
      year-old woman conceived with embryos derived from extracorporeal oocyte
      aspiration followed by IVM, embryo freezing, and frozen embryo transfer.
      CONCLUSION(S): A healthy live birth from extracorporeal aspiration of immature
      oocytes, IVM, and a frozen embryo transfer after 5 years was documented.
      Consideration of this technique should be made as a primary or adjunct
      intervention in the setting of fertility preservation.

PMID- 26297648
TI  - Quinol oxidase encoded by cyoABCD in Rhizobium etli CFN42 is regulated by ActSR
      and is crucial for growth at low pH or low iron conditions.
AB  - Rhizobium etli aerobically respires with several terminal oxidases. The quinol
      oxidase (Cyo) encoded by cyoABCD is needed for efficient adaptation to low oxygen
      conditions and cyo transcription is upregulated at low oxygen. This study sought
      to determine how transcription of the cyo operon is regulated. The 5' sequence
      upstream of cyo was analysed in silico and revealed putative binding sites for
      ActR of the ActSR two-component regulatory system. The expression of cyo was
      decreased in an actSR mutant regardless of the oxygen condition. As ActSR is
      known to be important for growth under low pH in another rhizobial species, the
      effect of growth medium pH on cyo expression was tested. As the pH of the media
      was incrementally decreased, cyo expression gradually increased in the WT,
      eventually reaching ~ 10-fold higher levels at low pH (4.8) compared with neutral
      pH (7.0) conditions. This upregulation of cyo under decreasing pH conditions was
      eliminated in the actSR mutant. Both the actSR and cyo mutants had severe growth
      defects at low pH (4.8). Lastly, the actSR and cyo mutants had severe growth
      defects when grown in media treated with an iron chelator. Under these
      conditions, cyo was upregulated in the WT, whereas cyo was not induced in the
      actSR mutant. Altogether, the results indicated cyo expression is largely
      dependent on the ActSR two-component system. This study also demonstrated
      additional physiological roles for Cyo in R. etli CFN42, in which it is the
      preferred oxidase for growth under acidic and low iron conditions.

PMID- 26297649
TI  - Planning future clinical trials in Machado Joseph disease: Lessons from a phase 2
      trial.
AB  - BACKGROUND: In a recent phase 2 clinical trial in spinocerebellar ataxia type
      3/Machado Joseph disease (SCA3/MJD), a neurogenetic disorder without specific
      therapy, benefits of lithium carbonate were found only on secondary efficacy
      outcomes, all related to ataxic features. In order to help designing future
      studies, we further analyzed the trial data searching for treatment response
      modifiers and metric properties of spinocerebellar ataxia (SCA) scales. METHODS:
      Efficacy analysis was performed with the Neurological Examination Score for the
      Assessment of Spinocerebellar Ataxia (NESSCA) and the Scale for the Assessment
      and Rating of Ataxia (SARA) subscores and with the subgroup of patients with
      independent gait according to the 8-meter walking-time (8MW). Interactions of
      clinical/molecular findings with treatment response, minimally important
      differences (MIDs), and sample size estimations for NESSCA, SARA, Spinocerebellar
      Ataxia Functional Index (SCAFI) and Composite Cerebellar Functional Score (CCFS)
      were evaluated. RESULTS: 62 SCA3/MJD patients had been randomly assigned (1:1)
      for the double-blind, placebo-controlled trial. While cerebellar NESSCA (range: 0
      7 points) differed between groups 0.64 points (95% CI 0.23 to 1.05, p<0.001) over
      the whole 48weeks of study, favoring lithium, no effect was found on non-ataxia
      subscores. Among patients able to perform the 8MW on baseline, NESSCA (p=0.010)
      and SCAFI (p=0.015) differed between groups favoring lithium. Finally, estimated
      sample sizes for the scales were provided. CONCLUSION: Lithium efficacy on
      cerebellar NESSCA, and on SCAFI and CCFS in the primary analysis, together with
      the lack of effect on non-ataxia features suggests that lithium should be tested
      in phase 3 trials in SCA3/MJD and that ataxia scales should be preferred to
      multisystem neurological instruments as the primary outcome. The inclusion of
      early stage patients is advisable in future clinical trials in SCA3/MJD. TRIAL
      REGISTRATION: clinicaltrials.gov identifier: NCT01096082.

PMID- 26297650
TI  - The correlation of isolated unilateral oculomotor paresis and pure midbrain
      stroke.

PMID- 26297652
TI  - Sinimarinibacterium flocculans gen. nov., sp. nov., a gammaproteobacterium from
      offshore surface seawater.
AB  - Two aerobic, rod-shaped, non-motile, non-sporulating and Gram-staining-negative
      bacterial strains, namely NH6-24T and Za3-11, were isolated from the surface
      seawater of the South China Sea and the estuary of the Yangtze River,
      respectively. The two isolates grew at 14-44  degrees C (optimum 37-40  degrees
      C) and pH 6.0-8.5 (optimum pH 7.0-7.5). The sea salt ranges for growth were 0.5
      10 % (w/v) (optimum 1-2.5 %) for strain NH6-24T and 0-12 % (w/v) (optimum 0.5-4.5
      %) for strain Za3-11.Both strains could grow in the absence of NaCl. Results of
      phylogenetic analysis based on 16S rRNA gene sequences indicated that the two
      isolates showed closest affinity to the genera Fontimonas (96.0 %) and Solimonas
      (94.1-95.1 %) and formed a single lineage in the cluster of the family
      Solimonadaceae. The predominant isoprenoid quinone was ubiquinone-8.The major
      fatty acids were C18 : 1omega7c, iso-C16 : 0 and C16 : 0.The dominant polar
      lipids were diphosphatidylglycerol, phosphatidylglycerol and
      phosphatidylethanolamine. The DNA G+C content was 65 mol%. Based on the
      polyphasic taxonomic characterization, strains NH6-24T and Za3-11 are considered
      to represent a novel species of a novel genus, for which the name
      Sinimarinibacterium flocculans gen. nov., sp. nov. is proposed. The type strain
      of the type species is NH6-24T ( = CGMCC 1.10815T = JCM 17607T) and an additional
      strain is Za3-11 ( = CGMCC 1.10816 = JCM 17606).

PMID- 26297653
TI  - Frailty Index and Quality of Life in Nursing Home Residents: Results From INCUR
      Study.
AB  - BACKGROUND: Frailty is a common clinical syndrome in older adults that carries an
      increased risk for poor health outcomes. The aim of this study was to examine the
      relationship between frailty and health-related Quality of Life (QoL) in older
      nursing home patients. METHODS: The study sample consisted of 590 patients aged
      65 years or older. QoL was measured with the Visual Analogue Scale. Frailty was
      assessed using the Frailty Index as proposed by Rockwood and colleagues. RESULTS:
      Mean age of the participants was 85.9 (standard deviation [SD] 7.6) years, with
      73.6% being female. The mean Frailty Index was 0.40 (SD 0.07) and the mean value
      of QoL was 67.4 out of 100 (SD 25.9). Before and after adjusting for age, and
      stratification for sociodemographic, and health-related variables, no significant
      associations between frailty and QoL were reported. CONCLUSION: In our study, the
      Frailty Index was not associated with QoL in nursing home residents.

PMID- 26297654
TI  - Cognitive Status at Hospital Admission: Postoperative Trajectory of Functional
      Recovery for Hip Fracture.
AB  - BACKGROUND: Cognitive impairment is common in the hip fracture patient
      population, yet few studies of functional recovery include this subgroup. The
      objective was to determine whether baseline cognition was a determinant of the
      rate of functional recovery over 6 months after hip fracture. METHODS: A
      consecutive cohort of 383 patients 65 years or older who were treated for hip
      fracture within a Canadian health region were grouped on cognitive status.
      Participants with Mini-Mental Status Examination scores <18 at 3-5 days
      postoperatively were classified as cognitively impaired. Primary outcome was the
      Functional Independence Measure. Interviews were completed within 5 days
      postoperatively (baseline), 1, 3, and 6 months postoperatively. Linear mixed
      modeling examined the pattern of recovery and the effect of cognitive status.
      RESULTS: Of the 383 participants, 104 (27%) had Mini-Mental Status Examination
      scores of less than 18. The effect size for changes in the FIM over 6 months was
      large for those without cognitive impairment (effect size = 2.3) and smaller for
      those with cognitive impairment (effect size = 0.9). After adjusting for age,
      gender, proxy respondent, and fracture type, participants with impaired cognition
      recovered more slowly, never attaining comparable levels with those without
      cognitive impairment. The 6-month health status for the cohort was substantially
      lower than the health status of age-gender-matched, community-dwelling adults.
      CONCLUSIONS: Patients with cognitive impairment who fracture their hips recover
      more slowly and achieve less functional recovery. Recovery is not uniform nor is
      it linear over the initial 6 months. The diversity of patient needs should be
      recognized postoperatively so that long-term recovery is optimized.

PMID- 26297655
TI  - Leg Muscle Mass and Foot Symptoms, Structure, and Function: The Johnston County
      Osteoarthritis Project.
AB  - BACKGROUND: Loss of muscle mass occurs with aging and in lower limbs it may be
      accelerated by foot problems. In this cross-sectional analysis, we evaluated the
      relationship of leg muscle mass to foot symptoms (presence or absence of pain,
      aching, or stiffness), structure while standing (high arch or low arch), and
      function while walking (pronated or supinated) in a community-based study of
      Caucasian and African American men and women who were 50-95 years old. METHODS:
      In the Johnston County Osteoarthritis Project, leg muscle mass was measured with
      whole body dual-energy x-ray absorptiometry, and plantar foot pressure data,
      using predetermined values, were used to classify foot structure and function.
      Sex-specific crude and adjusted (age, body mass index, and race) linear
      regression models examined associations of leg muscle mass index (Leg muscle mass
      [kg]/Height [m](2)) with foot symptoms, structure, and function. RESULTS:
      Complete data were available for 1,037 participants (mean age 68 years, mean body
      mass index 31 kg/m(2), 68% women, 29% African American). In women, pronated foot
      function was associated with lower leg muscle mass in crude (p = .02), but not
      adjusted (p = .22), models. A low arch was associated with a higher leg muscle
      mass in adjusted models for both men and women (p < .01). CONCLUSIONS: Leg muscle
      mass was associated with foot structure in our biracial sample, whereas relations
      between leg muscle mass and foot function were attenuated by age, body mass
      index, and race. Future longitudinal analyses are needed to explain the temporal
      relationship between these conditions and how they relate to other aspects of
      impairment and physical function.

PMID- 26297656
TI  - Frailty in Older Adults: A Nationally Representative Profile in the United
      States.
AB  - BACKGROUND: Frailty assessment provides a means of identifying older adults most
      vulnerable to adverse outcomes. Attention to frailty in clinical practice is more
      likely with better understanding of its prevalence and associations with patient
      characteristics. We sought to provide national estimates of frailty in older
      people. METHODS: A popular, validated frailty phenotype proposed by Fried and
      colleagues was applied to 7,439 participants in the 2011 baseline of the National
      Health and Aging Trends Study, a national longitudinal study of persons aged 65
      and older. All measures drew on a 2-hour in-person interview. Weighted estimates
      of frailty prevalence were obtained. RESULTS: Fifteen percent (95% CI: 14%, 16%)
      of the older non-nursing home population is frail, and 45% is prefrail (95% CI:
      44%, 47%). Frailty is more prevalent at older ages, among women, racial and
      ethnic minorities, those in supportive residential settings, and persons of lower
      income. Independently of these characteristics, frailty prevalence varies
      substantially across geographic regions. Chronic disease and disability
      prevalence increase steeply with frailty. Among the frail, 42% were hospitalized
      in the previous year, compared to 22% of the prefrail and 11% of persons
      considered robust. Hip, back, and heart surgery in the last year were associated
      with frailty. Over half of frail persons had a fall in the previous year.
      CONCLUSIONS: Our findings support the importance of frailty in late-life health
      etiology and potential value of frailty as a marker of risk for adverse health
      outcomes and as a means of identifying opportunities for intervention in clinical
      practice and public health policy.

PMID- 26297657
TI  - Plasma Klotho and Cognitive Decline in Older Adults: Findings From the InCHIANTI
      Study.
AB  - BACKGROUND: The hormone klotho, encoded by the gene klotho, is primarily
      expressed in the kidney and choroid plexus of the brain. Higher klotho
      concentrations and certain genetic variants of klotho have been linked to better
      cognition; however, it is unknown whether klotho relates prospectively to slower
      cognitive decline in older adults. METHODS: Plasma klotho was measured in 833
      participants aged 55 or older without dementia enrolled in InCHIANTI, a
      prospective cohort study comprising Italian adults. Cognition was measured by
      Mini-Mental State Examination (MMSE) and Trail-Making Tests A and B (Trails A and
      Trails B) at enrollment and at 3 and 6 years after enrollment. We assessed
      whether klotho concentrations measured at the 3-year visit related to cognition
      and cognitive decline. RESULTS: Each additional natural logarithm of klotho
      (pg/mL) was associated with 35% lower risk of meaningful decline in MMSE, defined
      as decline exceeding three points (relative risk = 0.65; 95% confidence interval
      0.45, 0.95; p value = .02), and 0.75-point smaller average 3-year decline
      (baseline to 3-year visit) in MMSE (95% confidence interval 0.02, 1.48; p value =
      .04). No statistically significant associations were found between klotho and
      declining Trails A (relative risk = 0.99; 95% confidence interval 0.75, 1.32; p
      value = .97) and B (relative risk = 1.02; 95% confidence interval 0.84, 1.24; p
      value = .82). CONCLUSIONS: Higher plasma klotho concentrations were associated
      with lower risk of meaningful decline and smaller average decline in MMSE. We did
      not observe such findings with Trails A and B, perhaps because they test
      executive function and motor skills, whereas MMSE measures global cognition.
      Future studies should investigate mechanisms through which klotho may affect
      domain-specific cognitive changes.

PMID- 26297658
TI  - COS-STAR: a reporting guideline for studies developing core outcome sets
      (protocol).
AB  - BACKGROUND: Core outcome sets can increase the efficiency and value of research
      and, as a result, there are an increasing number of studies looking to develop
      core outcome sets (COS). However, the credibility of a COS depends on both the
      use of sound methodology in its development and clear and transparent reporting
      of the processes adopted. To date there is no reporting guideline for reporting
      COS studies. The aim of this programme of research is to develop a reporting
      guideline for studies developing COS and to highlight some of the important
      methodological considerations in the process. METHODS/DESIGN: The study will
      include a reporting guideline item generation stage which will then be used in a
      Delphi study. The Delphi study is anticipated to include two rounds. The first
      round will ask stakeholders to score the items listed and to add any new items
      they think are relevant. In the second round of the process, participants will be
      shown the distribution of scores for all stakeholder groups separately and asked
      to re-score. A final consensus meeting will be held with an expert panel and
      stakeholder representatives to review the guideline item list. Following the
      consensus meeting, a reporting guideline will be drafted and review and testing
      will be undertaken until the guideline is finalised. The final outcome will be
      the COS-STAR (Core Outcome Set-STAndards for Reporting) guideline for studies
      developing COS and a supporting explanatory document. DISCUSSION: To assess the
      credibility and usefulness of a COS, readers of a COS development report need
      complete, clear and transparent information on its methodology and proposed core
      set of outcomes. The COS-STAR guideline will potentially benefit all stakeholders
      in COS development: COS developers, COS users, e.g. trialists and systematic
      reviewers, journal editors, policy-makers and patient groups.

PMID- 26297659
TI  - Deinococcus metalli sp. nov., isolated from an abandoned lead-zinc mine.
AB  - An aerobic, non-motile and Gram-staining-positive bacterial strain (1PNM-19T) was
      isolated from a lead-zinc ore in an abandoned mine and was investigated in a
      taxonomic study using a polyphasic approach. Phylogenetic analyses based on 16S
      rRNA gene sequences showed that strain 1PNM-19T was affiliated to the genus
      Deinococcus and most closely related to Deinococcus aquatilis DSM 23025T and
      Deinococcus ficus DSM 19119T. The major respiratory quinone was determined to be
      menaquinone 8 (MK-8) and the major fatty acids contained summed feature 3 (C16 :
      1omega7c and/or C16 : 1omega6c) and C16 : 0. A complex polar lipid profile
      consisted of different unidentified glycolipids and polar lipids, two
      unidentified aminolipids, an unidentified phosphoglycolipid, phospholipid and
      aminophospholipid. The genomic DNA G+C content of strain 1PNM-19T was 71.7 +/-
      0.1 mol%. Based on data from this taxonomic study, strain 1PNM-19T represents a
      novel species of the genus Deinococcus, for which the name Deinococcus metalli
      sp. nov. is proposed. The type strain is 1PNM-19T ( = GIMCC 1.654T = CCTCC AB
      2014198T = DSM 27521T).

PMID- 26297660
TI  - 60S ribosomal protein L35 regulates beta-casein translational elongation and
      secretion in bovine mammary epithelial cells.
AB  - 60S ribosomal protein L35 (RPL35) is an important component of the 60S ribosomal
      subunit and has a role in protein translation and endoplasmic reticulum (ER)
      docking. However, few studies have investigated RPL35 in eukaryotes and much
      remains to be learned. Here, we analyzed the function of RPL35 in beta-casein
      (CSN2) synthesis and secretion in bovine mammary epithelial cells (BMECs). We
      found that methionine (Met) could promote the expressions of CSN2 and RPL35.
      Analysis of overexpression and inhibition of RPL35 confirmed that it could
      mediate the Met signal and regulate CSN2 expression. The mechanism of CSN2
      regulation by RPL35 was analyzed by coimmunoprecipitation (Co-IP),
      colocalization, fluorescence resonance energy transfer (FRET) and gene mutation.
      We found that RPL35 could control ribosome translational elongation during
      synthesis of CSN2 by interacting with eukaryotic translational elongation factor
      2 (eEF2), and that eEF2 was the signaling molecule downstream of RPL35
      controlling this process. RPL35 could also control the secretion of CSN2 by
      locating it to the ER. Taken together, these results revealed that, RPL35 was an
      important positive regulatory factor involving in the Met-mediated regulation of
      CSN2 translational elongation and secretion. 

PMID- 26297661
TI  - Calpain-dependent regulation of the skeletal muscle atrophy following unloading.
AB  - Unloading causes rapid skeletal muscle atrophy due to increased protein
      degradation via activation of calpains and decreased protein synthesis. Our study
      elucidated role of calpain-1 in the regulation of ubiquitin proteasome pathway
      (UPP) and anabolic processes mediated by Akt-mTOR-p70S6K and MAPK-Erk (p90RSK)
      signaling. We hypothesized that blocking calpain will inhibit activation of UPP
      and decrease protein degradation resulting in reduction of unloading-induced
      skeletal muscle atrophy. Rats were divided into three groups: non-treated control
      (C), three day hindlimb suspension with (HSPD) or without (HS) treatment with
      calpain inhibitor PD150606. When compared with control PD150606 treatment during
      unloading: 1) attenuated loss of muscle mass, 2) prevented accumulation of
      calpain-1 (1.8-fold in HS vs 1.3-fold in HSPD) and ubiquitin (2.3-fold in HS vs
      0.7-fold in HSPD) mRNA and ubiquitinated proteins (1.6-fold in HS vs 0.8-fold in
      HSPD), 3) prevented decrease in the pAkt (0.4-fold in HS vs 1-fold in HSPD) and
      pFOXO3 (0.2-fold in HS vs 1.2-fold in HSPD) levels, 4) prevented increase in
      MAFbx (3.8-fold in HS vs 1.3-fold in HSPD) and eEF2k (1.8-fold in HS vs 0.6-fold
      in HSPD) mRNA. Our study indicates that blocking of calpain during unloading
      decreases skeletal muscle atrophy by inhibiting UPP activation and preserving
      anabolic signaling. 

PMID- 26297662
TI  - Streptomyces tyrosinilyticus sp. nov., a novel actinomycete isolated from river
      sediment.
AB  - A novel actinomycete, designated strain NEAU-Jh3-20(T), was isolated from river
      sediment collected from South river in Jilin Province, north China and
      characterized using a polyphasic approach. Phylogenetic analysis, based on 16S
      rRNA gene sequences, indicated that strain NEAU-Jh3-20(T) should be assigned to
      the genus Streptomyces and forms a distinct branch with its closest neighbour
      Streptomyces vitaminophilus DSM 41686(T)(97.09%). Moreover, key morphological and
      chemotaxonomic properties also confirmed the affiliation of strain NEAU-Jh3-20(T)
      to the genus Streptomyces. The cell wall contained ll-diaminopimelic acid and the
      whole-cell hydrolysates were glucose and ribose. The phospholipids were
      diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol,
      phosphatidylinositol mannosides and an unidentified phospholipid. The predominant
      menaquinones were MK-9(H8) and MK-9(H6). The major fatty acids were C16 : 0, C18
      : 0, anteiso-C15 : 0 and anteiso-C17 : 0. The DNA G+C content was 72.2 mol%. A
      combination of DNA-DNA hybridization results and some phenotypic characteristics
      demonstrated that strain NEAU-Jh3-20(T) could be distinguished from its closest
      phylogenetic relative. Therefore, it is proposed that strain NEAU-Jh3-20(T)
      represents a novel species of the genus Streptomyces, for which the name
      Streptomyces tyrosinilyticus sp. nov. is proposed. The type strain is NEAU-Jh3
      20(T) ( = CGMCC 4.7201(T)= DSM 42170(T)).

PMID- 26297663
TI  - A new case of de novo 6q24.2-q25.2 deletion on paternal chromosome 6 with growth
      hormone deficiency: a twelve-year follow-up and literature review.
AB  - BACKGROUND: Deletions on the distal portion of the long arm of chromosome 6 are
      relatively uncommon, and only a small number occurs in the paternal copy, causing
      growth abnormalities. As a result, extensive clinical descriptions are lacking.
      CASE PRESENTATION: We describe a male of Italian descent born at 35 weeks by
      elective caesarean delivery presenting hypoplastic left colon, bilateral inguinal
      hernia, dysplastic tricuspid and pulmonary valves, premature ventricular
      contractions, recurrent otitis media, poor feeding, gastro-oesophageal reflux,
      bilateral pseudopapilledema, and astigmatism. He also showed particular facial
      dysmorphisms and postnatal growth failure. Early psychomotor development was
      mildly delayed. At 3.75 years, he was evaluated for severe short stature (-2.98
      SD) and delayed bone age. He showed an insulin-like growth factor 1 concentration
      (IGF-1) in the low-normal range. Growth hormone stimulation tests showed a low
      response to clonidine and insulin. Magnetic resonance imaging showed hypophyseal
      hypoplasia. Genetic evaluation by Single Nucleotide Polymorphism arrays showed a
      de novo 6q24.2-q25.2 deletion on paternal chromosome 6. CONCLUSION: We confirm
      that this is a new congenital malformation syndrome associated with a deletion of
      6q24.2-q25.2 on paternal chromosome 6. We suggest evaluating the growth hormone
      axis in children with 6q24.2-q25.2 deletions and growth failure.

PMID- 26297665
TI  - Lachancea quebecensis sp. nov., a yeast species consistently isolated from tree
      bark in the Canadian province of Quebec.
AB  - A thorough sampling of maple, oak, birch, and apple tree bark in North America
      yielded a set of isolates that represent a yeast species not yet formally
      described. The strains obtained were all isolated from the Canadian province of
      Quebec. These four isolates have identical electrophoretic karyotypes, distinct
      from other species of the genus Lachancea, and are most closely related to the
      formally recognized species Lachancea thermotolerans according to the D1/D2
      domain of the LSU rDNA gene and 5.8S-ITS region. Previous studies revealed the
      existence of a population of strains closely related to L. thermotolerans, with
      unique D1/D2 sequences and the ability to grow on melibiose, which is also true
      for these isolates. The sequences obtained here (for the D1/D2, and 5.8S-ITS
      region) are identical among the four strains, and in a phylogenetic analysis of
      the D1/D2 region, the strains form a distinct clade with the previously described
      population closely related to L. thermotolerans, composed of isolates from Japan,
      as well as from the provinces of Ontario and Quebec in Canada. On the basis of
      select physiological and phylogenetic characteristics, a novel ascosporogenous
      yeast species, Lachancea quebecensis sp. nov., is proposed. The type strain
      LL11_022T ( = CBS 14138T = CLIB 1763T = UCDFST 15-106T) was isolated from maple
      tree bark in the Station Duchesnay, QC region of Quebec, Canada. The MycoBank
      number is MB811749.

PMID- 26297664
TI  - Visualization and quantification of simian immunodeficiency virus-infected cells
      using non-invasive molecular imaging.
AB  - In vivo imaging can provide real-time information and three-dimensional (3D) non
      invasive images of deep tissues and organs, including the brain, whilst allowing
      longitudinal observation of the same animals, thus eliminating potential
      variation between subjects. Current in vivo imaging technologies, such as
      magnetic resonance imaging (MRI), positron emission tomography-computed
      tomography (PET-CT) and bioluminescence imaging (BLI), can be used to pinpoint
      the spatial location of target cells, which is urgently needed for revealing
      human immunodeficiency virus (HIV) dissemination in real-time and HIV-1
      reservoirs during suppressive antiretroviral therapy (ART). To demonstrate that
      in vivo imaging can be used to visualize and quantify simian immunodeficiency
      virus (SIV)-transduced cells, we genetically engineered SIV to carry different
      imaging reporters. Based on the expression of the reporter genes, we could
      visualize and quantify the SIV-transduced cells via vesicular stomatitis virus
      glycoprotein pseudotyping in a mouse model using BLI, PET-CT or MRI. We also
      engineered a chimeric EcoSIV for in vivo infection study. Our results
      demonstrated that BLI is sensitive enough to detect as few as five single cells
      transduced with virus, whilst PET-CT can provide 3D images of the spatial
      location of as few as 10 000 SIV-infected cells. We also demonstrated that MRI
      can provide images with high spatial resolution in a 3D anatomical context to
      distinguish a small population of SIV-transduced cells. The in vivo imaging
      platform described here can potentially serve as a powerful tool to visualize
      lentiviral infection, including when and where viraemia rebounds, and how
      reservoirs are formed and maintained during latency or suppressive ART. 

PMID- 26297666
TI  - Next-generation sequencing shows West Nile virus quasispecies diversification
      after a single passage in a carrion crow (Corvus corone) in vivo infection model.
AB  - West Nile virus (WNV) occurs as a population of genetic variants (quasispecies)
      infecting a single animal. Previous low-resolution viral genetic diversity
      estimates in sampled wild birds and mosquitoes, and in multiple-passage
      adaptation studies in vivo or in cell culture, suggest that WNV genetic
      diversification is mostly limited to the mosquito vector. This study investigated
      genetic diversification of WNV in avian hosts during a single passage using next
      generation sequencing. Wild-captured carrion crows were subcutaneously infected
      using a clonal Middle-East WNV. Blood samples were collected 2 and 4 days post
      infection. A reverse-transcription (RT)-PCR approach was used to amplify the WNV
      genome directly from serum samples prior to next-generation sequencing resulting
      in an average depth of at least 700 *  in each sample. Appropriate controls were
      sequenced to discriminate biologically relevant low-frequency variants from
      experimentally introduced errors. The WNV populations in the wild crows showed
      significant diversification away from the inoculum virus quasispecies structure.
      By contrast, WNV populations in intracerebrally infected day-old chickens did not
      diversify from that of the inoculum. Where previous studies concluded that WNV
      genetic diversification is only experimentally demonstrated in its permissive
      insect vector species, we have experimentally shown significant diversification
      of WNV populations in a wild bird reservoir species. 

PMID- 26297667
TI  - PBB: definition, mechanisms, and treatment.

PMID- 26297668
TI  - Trends in Type of Health Insurance Coverage for US Children and Their Parents,
      1998-2011.
AB  - OBJECTIVE: To examine trends in health insurance type among US children and their
      parents. METHODS: Using the Medical Expenditure Panel Survey (1998-2011), we
      linked each child (n = 120,521; weighted n ~ 70 million) with his or her parent
      or parents and assessed patterns of full-year health insurance type, stratified
      by income. We examined longitudinal insurance trends using joinpoint regression
      and further explored these trends with adjusted regression models. RESULTS: When
      comparing 1998 to 2011, the percentage of low-income families with both child and
      parent or parents privately insured decreased from 29.2% to 19.1%, with an
      estimated decline of -0.86 (95% confidence interval, -1.10, -0.63) unadjusted
      percentage points per year; middle-income families experienced a drop from 74.5%
      to 66.3%, a yearly unadjusted percentage point decrease of -0.73 (95% confidence
      interval, -0.98, -0.48). The discordant pattern of publicly insured children with
      uninsured parents increased from 10.4% to 27.2% among low-income families and
      from 1.4% to 6.7% among middle-income families. Results from adjusted models were
      similar to joinpoint regression findings. CONCLUSIONS: During the past decade,
      low- and middle-income US families experienced a decrease in the percentage of
      child-parent pairs with private health insurance and pairs without insurance.
      Concurrently, there was a rise in discordant coverage patterns-mainly publicly
      insured children with uninsured parents.

PMID- 26297671
TI  - Corrigendum.

PMID- 26297669
TI  - What does independence mean?

PMID- 26297672
TI  - Inherited cardiomyopathies--Novel therapies.
AB  - Cardiomyopathies arising due to a single gene defect represent various pathways
      that evoke adverse remodeling and cardiac dysfunction. While the gene therapy
      approach is slowly evolving and has not yet reached clinical "prime time" and
      gene correction approaches are applicable at the bench but not at the bedside,
      major advances are being made with molecular and drug therapies. This review
      summarizes the contemporary drugs introduced or being tested to help manage these
      unique disorders bearing a major impact on the quality of life and survival of
      the affected individuals. The restoration of the RNA reading frame facilitates
      the expression of partly functional protein to salvage or alleviate the disease
      phenotype. Chaperones are used to prevent the degradation of abnormal but still
      functional proteins, while other molecules are given for pathogen silencing, to
      prevent aggregation or to enhance clearance of protein deposits. The absence of
      protein may be managed by viral gene delivery or protein therapy. Enzyme
      replacement therapy is already a clinical reality for a series of metabolic
      diseases. The progress in molecular biology, based on the knowledge of the gene
      defect, helps generate small molecules and pharmaceuticals targeting the key
      events occurring in the malfunctioning element of the sick organ. Cumulatively,
      these tools augment the existing armamentarium of phenotype oriented symptomatic
      and evidence-based therapies for patients with inherited cardiomyopathies. 

PMID- 26297673
TI  - Targeting oxidant-dependent mechanisms for the treatment of COPD and its
      comorbidities.
AB  - Chronic obstructive pulmonary disease (COPD) is an incurable global health burden
      and is characterised by progressive airflow limitation and loss of lung function.
      In addition to the pulmonary impact of the disease, COPD patients often develop
      comorbid diseases such as cardiovascular disease, skeletal muscle wasting, lung
      cancer and osteoporosis. One key feature of COPD, yet often underappreciated, is
      the contribution of oxidative stress in the onset and development of the disease.
      Patients experience an increased burden of oxidative stress due to the combined
      effects of excess reactive oxygen species (ROS) and nitrogen species (RNS)
      generation, antioxidant depletion and reduced antioxidant enzyme activity.
      Currently, there is a lack of effective treatments for COPD, and an even greater
      lack of research regarding interventions that treat both COPD and its
      comorbidities. Due to the involvement of oxidative stress in the pathogenesis of
      COPD and many of its comorbidities, a unique therapeutic opportunity arises where
      the treatment of a multitude of diseases may be possible with only one
      therapeutic target. In this review, oxidative stress and the roles of ROS/RNS in
      the context of COPD and comorbid cardiovascular disease, skeletal muscle wasting,
      lung cancer, and osteoporosis are discussed and the potential for therapeutic
      benefit of anti-oxidative treatment in these conditions is outlined. Because of
      the unique interplay between oxidative stress and these diseases, oxidative
      stress represents a novel target for the treatment of COPD and its comorbidities.

PMID- 26297674
TI  - Oryzobacter terrae gen. nov., sp. nov., isolated from paddy soil.
AB  - A bacterial strain, PSGM2-16(T), was isolated from a pot of paddy soil grown with
      rice in Suwon region, Republic of Korea, and was characterized as having aerobic,
      Gram-stain-positive, short-rod-shaped cells with one polar flagellum. The 16S
      rRNA gene sequence of strain PSGM2-16(T) revealed the highest sequence
      similarities with Knoellia locipacati DMZ1T (97.4%), Fodinibacter luteus YIM
      C003(T) (97.2%) and Lapillicoccus jejuensis R-Ac013(T) (97.0%), and the
      phylogenetic tree showed that strain PSGM2-16(T) formed a subgroup with
      Ornithinibacter aureus HB09001(T) and F. luteus YIM C003(T) within the family
      Intrasporangiaceae. The major fatty acids (>10% of the total fatty acids) of
      strain PSGM2-16(T) were iso-C16 : 0, C17 : 1omega8c and iso-C14 : 0. The
      predominant menaquinone was MK-8(H4). The polar lipids present were
      diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, three
      aminophospholipids and two phospholipids. The peptidoglycan was type A4gamma with
      meso-diaminopimelic acid as the diagnostic diamino acid. DNA-DNA hybridization
      values between strain PSGM2-16(T) and closely related taxa were much less than
      70%. The genomic DNA G+C content of strain PSGM2-16(T) was 70.0 mol%. On the
      basis of the evidence presented, it is concluded that strain PSGM2-16(T)
      represents a novel species of a new genus in the family Intrasporangiaceae, for
      which the name Oryzobacter terrae gen. nov., sp. nov. is proposed. The type
      strain of the type species is PSGM2-16(T) ( = KACC 17299(T)= DSM 27137(T)= NBRC
      109598(T)).

PMID- 26297675
TI  - The growth pattern of the human intestine and its mesentery.
AB  - BACKGROUND: It remains unclear to what extent midgut rotation determines human
      intestinal topography and pathology. We reinvestigated the midgut during its
      looping and herniation phases of development, using novel 3D visualization
      techniques. RESULTS: We distinguished 3 generations of midgut loops. The
      topography of primary and secondary loops was constant, but that of tertiary
      loops not. The orientation of the primary loop changed from sagittal to
      transverse due to the descent of ventral structures in a body with a still
      helical body axis. The 1st secondary loop (duodenum, proximal jejunum) developed
      intraabdominally towards a left-sided position. The 2nd secondary loop (distal
      jejunum) assumed a left-sided position inside the hernia before returning, while
      the 3rd and 4th secondary loops retained near-midline positions. Intestinal
      return into the abdomen resembled a backward sliding movement. Only after return,
      the 4th secondary loop (distal ileum, cecum) rapidly "slid" into the right lower
      abdomen. The seemingly random position of the tertiary small-intestinal loops may
      have a biomechanical origin. CONCLUSIONS: The interpretation of "intestinal
      rotation" as a mechanistic rather than a descriptive concept underlies much of
      the confusion accompanying the physiological herniation. We argue, instead, that
      the concept of "en-bloc rotation" of the developing midgut is a fallacy of
      schematic drawings. Primary, secondary and tertiary loops arise in a hierarchical
      fashion. The predictable position and growth of secondary loops is pre-patterned
      and determines adult intestinal topography. We hypothesize based on published
      accounts that malrotations result from stunted development of secondary loops.

PMID- 26297677
TI  - In vitro development of Haemoproteus columbae (Haemosporida: Haemoproteidae),
      with perspectives for genomic studies of avian haemosporidian parasites.
AB  - The evolutionary origin of wildlife and human malaria parasites (Plasmodium spp.)
      has been discussed for several decades. The lack of genomic data about species of
      wildlife haemosporidian parasites related to Plasmodium limits the number of taxa
      available for phylogenetic analysis. Genomic data about avian parasites of the
      genus Haemoproteus parasites, the sister genus to Plasmodium are still not
      available, mainly due to difficulties in obtaining pure DNA of parasites
      inhabiting nucleated avian host cells. Recent studies show that microgametes of
      Haemoproteus (Parahaemoproteus) spp. develop in vitro and can be isolated by
      simple centrifugation, allowing the isolation of pure parasite DNA for genomic
      studies. However, in vitro development of Haemoproteus (Haemoproteus) spp. has
      not been investigated, and it is unclear if microgametes of these parasites also
      can be obtained under in vitro conditions. Here, we provide the first data about
      the in vitro development of Haemoproteus (Haemoproteus) columbae, a widespread
      avian haemosporidian parasite, which is specific to pigeons and doves
      (Columbiformes) and is transmitted by hippoboscid flies (Diptera, Hippoboscidae).
      In vitro gametogenesis and ookinete development of H. columbae were studied using
      a strain isolated from a feral Rock Pigeon (Columba livia) in Bogota-Colombia.
      The morphological events leading to exflagellation, fertilization and ookinete
      formation, as well as the rate of development of these stages were followed in
      vitro at 40  degrees C, 19  degrees C and 15  degrees C for 48 h. Macrogametes,
      microgametes, zygotes and initial stages of ookinete development were observed in
      all temperatures, but mature ookinetes were seen only at 40  degrees C. The
      largest diversity of sporogonic stages of H. columbae were present at 40  degrees
      C however, exflagellation, fertilization of macrogametes and development of
      immature ookinetes were also observed at 15  degrees C and 19  degrees C.
      Morphological and morphometric features of these stages in vitro were described
      and illustrated. This study demonstrates a requirement of high temperature for
      the successful development of mature ookinetes of H. columbae, but not gametes.
      We show that 1) parasites of the H. (Haemoproteus) subgenus exflagellate in vitro
      at 15-19  degrees C, as is the case in H. (Parahaemoproteus) spp. and 2) in vitro
      exflagellation can be used to obtain pure DNA for genomic studies.

PMID- 26297676
TI  - Anaerobic respiration: In vitro efficacy of Nitazoxanide against mitochondriate
      Acanthamoeba castellanii of the T4 genotype.
AB  - Acanthamoeba is an opportunistic protist pathogen that is responsible for serious
      human and animal infection. Being one of the most frequently isolated protists
      from the environment, it is likely that it readily encounters microaerophilic
      environments. For respiration under anaerobic or low oxygen conditions in several
      amitochondriate protists, decarboxylation of pyruvate is catalyzed by pyruvate
      ferredoxin oxidoreductase instead of pyruvate dehydrogenase. In support,
      Nitazoxanide, an inhibitor of pyruvate ferredoxin oxidoreductase, is effective
      and non-mutagenic clinically against a range of amitochondriate protists, Giardia
      intestinalis, Entamoeba histolytica and Trichomonas vaginalis. The overall aim of
      the present study was to determine in vitro efficacy of Nitazoxanide against
      Acanthamoeba castellanii. At micromolar concentrations, the findings revealed
      that Nitazoxanide neither affected A. castellanii growth or viability nor amoeba
      mediated host cell monolayer damage in vitro or extracellular proteolytic
      activities. Similarly, microaerophilic conditions alone had no significant
      effects. In contrast, microaerophilic conditions together with Nitazoxanide
      showed amoebicidal effects and inhibited A. castellanii-mediated host cell
      monolayer damage as well as extracellular proteases. Using encystation assays, it
      was observed that Nitazoxanide inhibited trophozoite transformation into cysts
      both under aerophilic and microaerophilic conditions. Furthermore, pre-treatment
      of cysts with Nitazoxanide inhibited A. castellanii excystation. These findings
      are important in the identification of potential targets that could be useful
      against parasite-specific respiration as well as to understand the basic biology
      of the life cycle of Acanthamoeba. 

PMID- 26297678
TI  - Autophagy protein 12 plays an essential role in Acanthamoeba encystation.
AB  - Autophagy is a well conserved, catabolic process in eukaryotic cells. Previously,
      we identified two novel ubiquitin like conjugation systems (Atg12 and Atg8) in
      the autophagy process of Acanthamoeba castellanii. To obtain more specific
      information on the Atg12 ubiquitin like conjugation system during encystation of
      Acanthamoeba, we characterized the function of Atg12. Knockdown of AcAg12 in
      trophozoites resulted in inhibition of cyst formation. Analysis of subcellular
      localization showed that AcAtg12 was evenly distributed in the trophozoites
      during early encystation, started to accumulate partially as dots or fragments,
      and then co-localized with the vesicle of the autophagic structure. However, the
      mRNA expression of AcAtg12 was maintained at a constant level during encystation
      as well as in trophozoites. Ultrastructural analysis with TEM showed that AcAtg12
      knockdown cells showed vacuolization, lack of cyst wall formation, and numerical
      decline of autophagic structures, compared with the control cells. Interestingly,
      these knockdown cells began to round-up and swell, and then burst at 144 h post
      encystation. Taken together, our results might provide a better understanding of
      the Atg12 UBL conjugation system in Acanthamoeba and other cyst forming protozoan
      parasites. 

PMID- 26297679
TI  - Heme proteins of Giardia intestinalis.
AB  - Among the few organisms that cannot make the iron cofactor heme, some nonetheless
      possess heme proteins. This includes the protozoan parasite Giardia intestinalis,
      which encodes five known heme proteins: a flavohemoglobin and four members of the
      cytochrome b5 family. Giardia flavohemoglobin closely resembles those of the
      Enterobacteriaceae in structure and function, acting as a nitric oxide
      dioxygenase that is induced when trophozoites are exposed to reactive nitrogen
      species. The Giardia cytochromes b5 are soluble proteins having relatively low
      reduction potentials and lack several features that are expected to promote rapid
      electron transfer with redox partners. Only one potential electron donor, and no
      electron acceptors, have yet been identified in the Giardia genome, and the roles
      of these cytochromes are presently unknown. The answer may lie in the sequences
      that flank the heme-binding core of these proteins which could serve to localize
      them within the cell through reversible post-translational modifications and to
      promote specific protein-protein interactions. 

PMID- 26297680
TI  - Rapid concentration and sensitive detection of hookworm ova from wastewater
      matrices using a real-time PCR method.
AB  - The risk of human hookworm infections from land application of wastewater
      matrices could be high in regions with high hookworm prevalence. A rapid,
      sensitive and specific hookworm detection method from wastewater matrices is
      required in order to assess human health risks. Currently available methods used
      to identify hookworm ova to the species level are time consuming and lack
      accuracy. In this study, a real-time PCR method was developed for the rapid,
      sensitive and specific detection of canine hookworm (Ancylostoma caninum) ova
      from wastewater matrices. A. caninum was chosen because of its morphological
      similarity to the human hookworm (Ancylostoma duodenale and Necator americanus).
      The newly developed PCR method has high detection sensitivity with the ability to
      detect less than one A. caninum ova from 1 L of secondary treated wastewater at
      the mean threshold cycle (CT) values ranging from 30.1 to 34.3. The method is
      also able to detect four A. caninum ova from 1 L of raw wastewater and from ~4 g
      of treated sludge with mean CT values ranging from 35.6 to 39.8 and 39.8 to 39.9,
      respectively. The better detection sensitivity obtained for secondary treated
      wastewater compared to raw wastewater and sludge samples could be attributed to
      sample turbidity. The proposed method appears to be rapid, sensitive and specific
      compared to traditional methods and has potential to aid in the public health
      risk assessment associated with land application of wastewater matrices.
      Furthermore, the method can be adapted to detect other helminth ova of interest
      from wastewater matrices. 

PMID- 26297681
TI  - Bone marrow-derived cells migrate to the liver and contribute to the generation
      of different cell types in chronic Schistosoma mansoni infection.
AB  - The main pathogenic event caused by Schistosoma mansoni infection is
      characterized by a granulomatous inflammatory reaction around parasite eggs and
      fibrosis in the liver. We have previously shown that transplantation of bone
      marrow cells (BMC) promotes a reduction in liver fibrosis in chronically S.
      mansoni-infected mice. Here we investigated the presence and phenotype of bone
      marrow-derived cells in livers of S. mansoni-infected mice. During the chronic
      phase of infection, C57BL/6 mice had an increased number of circulating
      mesenchymal stem cells and endothelial progenitor cells in the peripheral blood
      when compared to uninfected controls. In order to investigate the fate of BMC in
      the liver, we generated bone marrow chimeric mice by transplanting BMC from
      transgenic green fluorescent protein (GFP) mice into lethally irradiated wild
      type C57BL/6 mice. S. mansoni-infected chimeric mice did not demonstrate
      increased mortality and developed similar liver histopathological features, when
      compared to wild-type S. mansoni-infected mice. GFP(+) bone marrow-derived cells
      were found in the liver parenchyma, particularly in periportal regions.
      CD45(+)GFP(+) cells were found in the granulomas. Flow cytometry analysis of
      digested liver tissue characterized GFP(+) cells as lymphocytes, myeloid cells
      and stem cells. GFP(+) cells were also found in areas of collagen deposition,
      although rare GFP(+) cells expressed the myofibroblast cell marker alpha-SMA.
      Additionally GFP(+) endothelial cells (co-stained with von Willebrand factor)
      were frequently observed, while BMC-derived hepatocytes (GFP(+) albumin(+) cells)
      were sparsely found in the liver of chimeric mice chronically infected with S.
      mansoni. In conclusion, BMC are recruited to the liver during chronic
      experimental infection with S. mansoni and contribute to the generation of
      different cell types involved, not only in disease pathogenesis, but possibly in
      liver regeneration and repair. 

PMID- 26297682
TI  - Presence of a thapsigargin-sensitive calcium pump in Trypanosoma evansi:
      Immunological, physiological, molecular and structural evidences.
AB  - In higher eukaryotes, the sarco-endoplasmic reticulum (ER) Ca(2+)-ATPase (SERCA)
      is characterized for its high sensitivity to low concentrations of thapsigargin
      (TG), a very specific inhibitor. In contrast, SERCA-like enzymes with different
      sensitivities to TG have been reported in trypanosomatids. Here, we characterized
      a SERCA-like enzyme from Trypanosoma evansi and evaluated its interaction with
      TG. Confocal fluorescence microscopy using BODIPY FL TG and specific anti-SERCA
      antibodies localized the T. evansi SERCA-like enzyme in the ER and confirmed its
      direct interaction with TG. Moreover, the use of either 1 MUM TG or 25 MUM 2',5'
      di (tert-butyl)-1,4-benzohydroquinone prevented the reuptake of Ca(2+) and
      consequently produced a small increase in the parasite cytosolic calcium
      concentration in a calcium-free medium, which was released from the ER pool. A
      3035 bp-sequence coding for a protein with an estimated molecular mass of 110.2
      kDa was cloned from T. evansi. The corresponding gene product contained all the
      invariant residues and conserved motifs found in other P-type ATPases but lacked
      the calmodulin binding site. Modeling of the three-dimensional structure of the
      parasite enzyme revealed that the amino acid changes found in the TG-SERCA
      binding pocket do not compromise the interaction between the enzyme and the
      inhibitor. Therefore, we concluded that T. evansi possesses a SERCA-like protein
      that is inhibited by TG. 

PMID- 26297683
TI  - Performance of a real time PCR for leishmaniasis diagnosis using a L. (L.)
      infantum hypothetical protein as target in canine samples.
AB  - Visceral leishmaniasis represents an important public health issue in different
      parts of the world, requiring that measures be put in place to control the spread
      of the disease worldwide. The canine leishmaniasis diagnosis is not easy based on
      clinical signs, since dogs may not develop the infection with recognizable signs.
      Thus, the laboratorial diagnosis is essential to ascertain the incidence and
      prevalence of canine leishmaniasis especially in areas with major control
      efforts. Although, the diagnosis can be performed by the use of different
      approaches, the molecular methods such as PCR have become an indispensable tool
      for leishmaniases diagnosis. A TaqMan assay for real-time PCR (Linj31-qPCR) was
      developed to determine the parasite occurrence in clinical cases of
      leishmaniasis. The assay targets an L. (L.) infantum hypothetical protein region.
      The specificity of the assay was verified by using Leishmania World Health
      Organization reference strains including parasites belonging to subgenus L.
      (Leishmania), subgenus L. (Viannia), other Leishmania species and Trypanosoma
      cruzi. The sensitivity was verified by using isolates of L. (L.) amazonensis and
      L. (L.) infantum. The usefulness of the assay for diagnosis was ascertained by
      testing 277 samples from dogs in regions endemic for visceral and/or cutaneous
      leishmaniasis and from regions in which leishmaniasis was not endemic in Sao
      Paulo State, Brazil. Diagnosis of canine visceral leishmaniasis (CVL) was
      determined on these animals by conventional PCR and three serological tests. The
      dog samples were divided into four groups. I, dogs with CVL (n = 101); II, dogs
      with other diseases and without CVL (n = 97); III, dogs with American cutaneous
      leishmaniasis (n = 7), and, IV, dogs without CVL (n = 72) from areas where
      leishmaniasis was not endemic as control group. Results indicated that Linj31
      qPCR was able to identify parasites belonging to subgenus L. (Leishmania) with no
      cross-amplification with other parasite subgenera. The Linj31-qPCR detected
      Leishmania parasites DNA in 98% of samples from Group I. In conclusion this
      methodology can be used as routine diagnostic tools to detect parasites from
      subgenus Leishmania. 

PMID- 26297684
TI  - AMP-activated protein kinase attenuates oxLDL uptake in macrophages through
      PP2A/NF-kappaB/LOX-1 pathway.
AB  - The differentiation of macrophages into lipid-laden foam cells is a hallmark in
      early-stage atherosclerosis. The developmental role of adenosine monophosphate
      activated protein kinase (AMPK) in a transformation of foam cells, especially in
      macrophage cholesterol uptake that remains undetermined. Here we demonstrate that
      AMPK activation in response to IMM-H007 or AICAR resulted in a decrease in
      macrophage cholesterol uptake and thus inhibited foam cell formation in
      macrophages mediated by oxidized low-density lipoprotein (oxLDL). This functional
      change was caused by a downregulation of mRNA and protein expression of LOX-1 but
      not other scavenger receptors, including scavenger receptor-A (SR-A), CD36 and
      scavenger receptor-BI (SR-BI). The expression of LOX-1 was regulated by AMPK
      activation induced decreased phosphorylation of nuclear transcription factor NF
      kappaB, since siRNA interference or dominant negative AMPK overexpression
      significantly promotes Ser536 dephosphorylation of NF-kappaB p65 and thus
      increases LOX-1 expression. Moreover, pharmacological AMPK activation was shown
      to promote protein phosphatase 2A (PP2A) activity and the specific PP2A
      inhibitor, okadaic acid, could prevent the effects of IMM-H007 or AICAR on NF
      kappaB and LOX-1. In vivo, pharmacological AMPK activation reduced the lesion
      size of atherosclerosis and the expression of LOX-1 in aortas in apolipoprotein E
      deficient mice. Our current findings suggest a novel mechanism of LOX-1
      regulation by AMPK to attenuate macrophage oxLDL uptake and atherosclerosis.

PMID- 26297685
TI  - Resistance to cellular HIV infection.

PMID- 26297686
TI  - Telomere length and age-at-menopause in the US.
AB  - OBJECTIVES: Age-at-menopause and leukocyte telomere length (LTL) are both
      associated with biologic aging. Therefore, it would be reasonable to hypothesize
      that LTL may also serve as a marker for reproductive aging as shorter LTL may be
      associated with earlier age-at-menopause. METHODS: We analyzed data from 799 post
      menopausal (ages 41-85) participants in the National Health and Nutrition
      Examination Survey (1999-2002), a nationally representative sample of U.S. women.
      RESULTS: Controlling for behavioral, socio-demographic, and health-related
      determinants of menopause, we found that among non-Hispanic white women, an
      increase of one standard deviation in LTL was associated with a 0.43 year higher
      reported age-at-menopause. Among Mexican-Americans, an increase of one standard
      deviation in LTL was associated with a 1.56 year earlier menopause. There was no
      significant association between LTL and age-at-menopause among non-Hispanic black
      women. CONCLUSIONS: Our main finding is evidence of a strong interaction by
      race/ethnicity in the association between LTL and age-at-menopause. This evidence
      does not support the hypothesis that shorter LTL is a predictor of earlier age-at
      menopause, as the magnitude and direction of the associations between LTL and age
      at-menopause varied across racial/ethnic groups.

PMID- 26297687
TI  - Uterine stem cells--promise and possibilities.
AB  - A fraction of cells residing in the uterine endometrium exhibit functional
      pluripotent potential, allowing them to be classified as adult stem cells. While
      the physiological relevance of this cell population is mostly conjectural at this
      juncture, uterine endometrial stem cells (UESC's) may underline pathogenesis of
      certain common gynecological disorders, such as endometriosis and adenomyosis.
      The ease of access and harvesting of UESC's and the diverse differentiation
      potential of this cell population has identified the uterine endometrium as a
      valuable source of autologous stem cells that can be harnessed through judicious
      application of principals of regenerative medicine. This mini review offers a
      glimpse into the journey, and an introduction to the spectrum of disorders that
      UESC's have the potential of impacting. 

PMID- 26297688
TI  - Mapping brain Fos immunoreactivity in response to water deprivation and partial
      rehydration: Influence of sodium intake.
AB  - Water deprivation (WD) followed by water intake to satiety, produces satiation of
      thirst and partial rehydration (PR). Thus, WD-PR is a natural method to
      differentiate thirst from sodium appetite. WD-PR also produces Fos
      immunoreactivity (Fos-ir) in interconnected areas of a brain circuit postulated
      to subserve sodium appetite. In the present work, we evaluated the effect of
      sodium intake on Fos-ir produced by WD-PR in brain areas operationally defined
      according to the literature as either facilitatory or inhibitory to sodium
      intake. Isotonic NaCl was available for ingestion in a sodium appetite test
      performed immediately after a single episode of WD-PR. Sodium intake decreased
      Fos-ir in facilitatory areas such as the lamina terminalis (particularly
      subfornical organ and median preoptic nucleus), central amygdala and hypothalamic
      parvocellular paraventricular nucleus in the forebrain. Sodium intake also
      decreased Fos-ir in inhibitory areas such as the area postrema, lateral
      parabrachial nucleus and nucleus of the solitary tract in the hindbrain. In
      contrast, sodium intake further increased Fos-ir that was activated by water
      deprivation in the dorsal raphe nucleus, another inhibitory area localized in the
      hindbrain. WD-PR increased Fos-ir in the core and shell of the nucleus accumbens.
      Sodium intake reduced Fos-ir in both parts of the accumbens. In summary, sodium
      intake following WD-PR reduced Fos-ir in most facilitatory and inhibitory areas,
      but increased Fos-ir in another inhibitory area. It also reduced Fos-ir in a
      reward area (accumbens). The results suggest a functional link between sodium
      intake and the activity of the hindbrain-forebrain circuitry subserving reward
      and sodium appetite in response to water deprivation. 

PMID- 26297689
TI  - Predictors of "Liking" Three Types of Health and Fitness-Related Content on
      Social Media: A Cross-Sectional Study.
AB  - BACKGROUND: Adolescence and young adulthood are key periods for developing norms
      related to health behaviors and body image, and social media can influence these
      norms. Social media is saturated with content related to dieting, fitness, and
      health. Health and fitness-related social media content has received significant
      media attention for often containing objectifying and inaccurate health messages.
      Limited research has identified problematic features of such content, including
      stigmatizing language around weight, portraying guilt-related messages regarding
      food, and praising thinness. However, no research has identified who is "liking"
      or "following" (ie, consuming) such content. OBJECTIVE: This exploratory study
      aimed to identify demographics, mental health, and substance use-related
      behaviors that predicted consuming 3 types of health and fitness-related social
      media content-weight loss/fitness motivation pages (ie, "fitspiration"),
      detox/cleanse pages, and diet/fitness plan pages-among young social media users.
      METHODS: Participants (N=1001; age: median 21.06, IQR 17.64-24.64; female:
      723/1001, 72.23%) completed a cross-sectional 112-question online survey aimed at
      social media users aged between 15-29 years residing in Victoria, Australia.
      Logistic regression was used to determine which characteristics predicted
      consuming the 3 types of health and fitness-related social media content.
      RESULTS: A total of 378 (37.76%) participants reported consuming at least 1 of
      the 3 types of health and fitness-related social media content: 308 (30.77%)
      fitspiration pages, 145 (14.49%) detox pages, and 235 (23.48%) diet/fitness plan
      pages. Of the health and fitness-related social media content consumers, 85.7%
      (324/378) identified as female and 44.8% (324/723) of all female participants
      consumed at least 1 type of health and fitness-related social media content.
      Predictors of consuming at least one type of health and fitness-related social
      media content in univariable analysis included female gender (OR 3.5, 95% CI 2.5
      4.9, P<.001), being aged 15-17 years (OR 3.0, 95% CI 2.2-4.0, P<.001), residing
      outside a major city (OR 2.0, 95% CI 1.4-2.9, P<.001), having no post-high school
      education (OR 2.2, 95% CI 1.7-2.9, P<.001), being born in Australia (OR 2.0, 95%
      CI 1.2-3.2, P=.006), having a self-reported eating disorder (OR 2.4, 95% CI 1.5
      3.9, P<.001), being a victim of bullying (OR 1.7, CI 1.3-2.3, P<.001), misusing
      detox/laxative teas or diet pills (OR 4.6, 95% CI 2.8-7.6, P<.001), never using
      illegal drugs (OR 1.6, 95% CI 1.2-2.0, P=.001), and not engaging in risky single
      occasion drinking on a weekly basis (OR 2.0, 95% CI 1.3-3.0, P=.003).
      CONCLUSIONS: Consumers of health and fitness-related social media content were
      predominantly teenaged girls. There is a need to ensure that this social media
      content portrays responsible health messages and to research further the role of
      fitspiration pages, detox pages, and diet/fitness plan pages in influencing body
      image and health behaviors.

PMID- 26297690
TI  - Ten Year Follow-Up of Gap Balanced, Rotating Platform Total Knee Arthroplasty in
      Patients Under 60 Years of Age.
AB  - 68 patients (91 primary total knee arthroplasties) were evaluated at a mean 10
      year, minimum 5 year follow up in patients younger than sixty years of age
      utilizing the gap balanced, rotating platform design. Follow up assessment
      included implant survivorship, adverse events, x-rays, Knee Society rating system
      and clinical evaluation. Three revisions were performed with only one for aseptic
      loosening at 45 months. Two manipulations were performed in the early
      postoperative period. Survivorship of the rotating platform, gap balanced knee
      was 96.7% using surgical revision for any reason and 98.9% using aseptic
      loosening as endpoints. The rotating platform design using the gap balancing
      technique in young patients had excellent survivorship at 10-year mean follow up.

PMID- 26297691
TI  - Simultaneous Bilateral Versus Unilateral Total Knee Arthroplasty: A Comparison of
      30-Day Readmission Rates and Major Complications.
AB  - We queried the National Surgical Quality Improvement Program to compare the rate
      of 30-day readmissions and major complications between simultaneous bilateral and
      unilateral total knee arthroplasty (TKA). We identified 1771 patients who
      underwent simultaneous (same-day) bilateral TKA and matched them to a control
      group of 6790 patients who underwent unilateral TKA. The simultaneous bilateral
      TKA patients had longer surgery, were more commonly performed under general
      anesthesia, had a higher rate of postoperative transfusion, and a greater
      proportion of patients discharged to rehabilitation facilities. Simultaneous
      bilateral TKA has a low incidence of major complications and was not associated
      with more readmissions as compared to unilateral TKA (3.6% versus 3.5%
      respectively). Nonetheless, the odds of major complications was slightly higher
      following simultaneous bilateral TKA (OR=1.58). 

PMID- 26297692
TI  - Physiologically based pharmacokinetic modeling of ethyl acetate and ethanol in
      rodents and humans.
AB  - A physiologically based pharmacokinetic (PBPK) model was developed and applied to
      a metabolic series approach for the ethyl series (i.e., ethyl acetate, ethanol,
      acetaldehyde, and acetate). This approach bases toxicity information on dosimetry
      analyses for metabolically linked compounds using pharmacokinetic data for each
      compound and toxicity data for parent or individual compounds. In vivo
      pharmacokinetic studies of ethyl acetate and ethanol were conducted in rats
      following IV and inhalation exposure. Regardless of route, ethyl acetate was
      rapidly converted to ethanol. Blood concentrations of ethyl acetate and ethanol
      following both IV bolus and infusion suggested linear kinetics across blood
      concentrations from 0.1 to 10 mM ethyl acetate and 0.01-0.8 mM ethanol. Metabolic
      parameters were optimized and evaluated based on available pharmacokinetic data.
      The respiratory bioavailability of ethyl acetate and ethanol were estimated from
      closed chamber inhalation studies and measured ventilation rates. The resulting
      ethyl series model successfully reproduces blood ethyl acetate and ethanol
      kinetics following IV administration and inhalation exposure in rats, and blood
      ethanol kinetics following inhalation exposure to ethanol in humans. The
      extrapolated human model was used to derive human equivalent concentrations for
      the occupational setting of 257-2120 ppm ethyl acetate and 72-517 ppm ethyl
      acetate for continuous exposure, corresponding to rat LOAELs of 350 and 1500 ppm.

PMID- 26297693
TI  - Simple Neurectomy Versus Neurectomy With Intramuscular Implantation for
      Interdigital Neuroma: A Comparative Study.
AB  - BACKGROUND: Simple neurectomy is a standard treatment of interdigital nerve
      neuroma after failure of conservative treatment. Recently, neurectomy with
      intramuscular implantation of the proximal nerve stump has been proposed as a
      safe and effective alternative method providing significant pain improvement.
      However, there remains little evidence supporting one technique over the other.
      The purpose of this study was to compare functional outcomes and complications of
      simple neurectomy versus neurectomy with intramuscular implantation. METHODS:
      Retrospective chart review along with prospectively collected data of 99
      consecutive patients (105 feet with 118 neuromas) who were diagnosed with
      interdigital neuroma of the foot and underwent simple neurectomy (66 patients /
      72 feet / 78 neuromas) and neurectomy with intramuscular implantation of proximal
      nerve stump into intrinsic muscle of foot (33 patients / 33 feet / 40 neuromas)
      between 2000 and 2013. The minimum follow-up to be included in the study was 6
      months for both techniques (mean = 44.6 months, range = 6 to 150 months for
      simple neurectomy; and mean = 19.3 months, range = 6 to 66 months for neurectomy
      with intramuscular implantation of proximal nerve stump into the intrinsic
      muscle). The primary outcomes were Foot Function Index (FFI); pain, disability,
      activity limitation, and total score, Short Form-36 (SF-36: physical and mental
      component scores); and visual analog scale (VAS). Secondary outcomes included
      operative time and complications. Pre- and postoperative SF-36, and FFI, and pain
      (VAS) scores were obtained and compared using a paired t test. An independent t
      test was used to assess the functional outcomes and operative time between the 2
      groups, and a chi-square test was used to compare the complications between the 2
      techniques. RESULTS: Both groups demonstrated significant improvement of
      postoperative functional outcomes (FFI, SF-36, and VAS; P < .001, all) compared
      to the preoperative period. Neurectomy with intramuscular implantation
      demonstrated significant improvement of pain compared to simple neurectomy as
      measured with VAS (P = .002); however, the operative time was significantly
      longer than the simple neurectomy technique (P = .001). The rest of the
      functional outcomes measured were comparable between the 2 techniques.
      Complications in both simple neurectomy and implantation techniques were
      persistent pain (11.5% vs. 2.5%, P = .07), revision rate (5.1% vs. 0.0%, P =
      .08), and painful scar (5.1% vs. 5.0%, P = .83), respectively, but it did not
      reach statistical significance (P > .05, all). CONCLUSION: Both simple neurectomy
      and neurectomy with intramuscular implantation demonstrated significant
      improvement in terms of functional outcomes as measured with the FFI, SF-36, and
      VAS in patients with interdigital neuroma. Although requiring a longer operative
      time, neurectomy with intramuscular implantation technique might offer superior
      pain relief with comparable complications to the simple neurectomy technique.

PMID- 26297694
TI  - Creating a Supportive Environment: Peer Support Groups for Psychotic Disorders.
AB  - People with psychotic disorders frequently experience significant mental and
      social limitations that may result in persisting social isolation. Research has
      shown that a supportive social environment is crucial for the process of personal
      recovery. Peer support groups can provide an opportunity to reduce isolation and
      enhance the process of personal recovery. It encourages people to express their
      thoughts, feelings, and personal concerns in a peer-to-peer learning environment.
      Although the importance of peer support groups for various chronic diseases is
      widely acknowledged, they do not generally form part of routine care for people
      with psychotic disorders. The evidence base is promising, but the field could
      benefit from more rigorous, pragmatic trials with follow-up measurements to
      establish a solid evidence-base. This article briefly reviews the literature and
      discusses the barriers to implementation of a peer-support learning environment
      in routine care, as well as ways to overcome these. 

PMID- 26297695
TI  - Surgical Rescue: An Essential Component of Acute Care Surgery.

PMID- 26297696
TI  - Too Many Unanswered Questions in Children's Forearm Shaft Fractures: High
      Standard Epidemiological and Clinical Research in Pediatric Trauma is Warranted.

PMID- 26297698
TI  - Brain tumours in paediatrics: when should they be suspected?

PMID- 26297697
TI  - Head injury from falls in children younger than 6 years of age.
AB  - The risk of serious head injury (HI) from a fall in a young child is ill defined.
      The relationship between the object fallen from and prevalence of intracranial
      injury (ICI) or skull fracture is described. METHOD: Cross-sectional study of HIs
      from falls in children (<6 years) admitted to UK hospitals, analysed according to
      the object fallen from and associated Glasgow Coma Score (GCS) or alert, voice,
      pain, unresponsive (AVPU) and CT scan results. RESULTS: Of 1775 cases ascertained
      (median age 18 months, 54.7% boys), 87% (1552) had a GCS=15/AVPU=alert. 19.3%
      (342) had a CT scan: 32% (110/342) were abnormal; equivalent to 5.9% of the
      overall population, 16.9% (58) had isolated skull fractures and 13.7% (47) had
      ICI (49% (23/47) had an associated skull fracture). The prevalence of ICI
      increased with neurological compromise; however, 12% of children with a
      GCS=15/AVPU=alert had ICI. When compared to falls from standing, falls from a
      person's arms (233 children (mean age 1 year)) had a significant relative OR for
      a skull fracture/ICI of 6.94 (95% CI 3.54 to 13.6), falls from a building (eg,
      window or attic) (mean age 3 years) OR 6.84 (95% CI 2.65 to 17.6) and from an
      infant or child product (mean age 21 months) OR 2.75 (95% CI 1.36 to 5.65).
      CONCLUSIONS: Most HIs from a fall in these children admitted to hospital were
      minor. Infants, dropped from a carer's arms, those who fell from infant products,
      a window, wall or from an attic had the greatest chance of ICI or skull fracture.
      These data inform prevention and the assessment of the likelihood of serious
      injury when the object fallen from is known.

PMID- 26297699
TI  - Should children with overweight or obesity be excluded from height references?
AB  - BACKGROUND AND OBJECTIVES: Growth reference charts are usually based on
      measurements of children free from a medical condition that affects growth.
      However, samples collected during the past decades often contain a large
      proportion of overweight or obese children. Because obesity increases linear
      growth, the question arises to what extent the percentiles curves for
      length/height are affected by the presence of children with overweight or
      obesity. METHODS: Data from two cross-sectional samples of 2-year-old to 18-year
      old children were analysed: 12,252 Belgian children, measured in 2002-2004, and
      6159 Norwegian children, measured in 2003-2006. The LMS method was used to
      estimate height-for-age curves with and without children considered overweight or
      obese according to the International Obesity Task Force thresholds. RESULTS: The
      prevalence of overweight (including obesity) and obesity was 13.0% and 2.8% in
      the Belgian and 13.8% and 2.3% in the Norwegian sample. Children were taller when
      overweight (+0.49 and 0.43 SD, in the Belgian and Norwegian sample, respectively)
      or obese (+0.73 and 0.72 SD in the Belgian and Norwegian sample, respectively).
      Effect sizes were smaller in younger and older children, which points to an
      advanced age of maturation as a possible cause. Excluding overweight and obese
      children had only a minor impact on the growth curves with largest difference in
      mean height SD scores -0.09 in the Belgian and -0.12 in the Norwegian sample with
      a corresponding increase of up to 0.5% and 1.2% in number of children >+2 SD.
      CONCLUSIONS: Current Belgian and Norwegian growth references for length/height
      were found to be largely unaffected by the current proportion of overweight and
      obese children. There is, therefore, no need for revised height charts that
      exclude overweight or obese children.

PMID- 26297700
TI  - Presentation of childhood cancers to a paediatric shared care unit.
AB  - OBJECTIVE: To describe the pathways by which children with cancer present to a
      shared care oncology unit. DESIGN: A population-based retrospective cohort study
      of children diagnosed with cancer between the years 2004 and 2014. SETTING:
      District General Hospital with a level 2 Paediatric Oncology Shared Care Unit.
      PATIENTS: 93 children aged 0-15 years . OUTCOME MEASURES: Time to presentation
      (TTP) was defined as time from initial symptoms to time seen by secondary
      paediatrics. Time to diagnosis (TTD) was defined as time from initial symptoms to
      diagnosis at a Principal Treatment Centre. Patient pathways to diagnosis were
      mapped and routes for different cancers were compared. RESULTS: Only 2/93 cases
      (2.1%) in 10 years were referred via the 2-week pathway. Most presentations were
      acute via immediate general practitioner (GP) referral or self-referral to the
      emergency department 62/93 (67%). Leukaemia presented acutely and via the GP more
      often than via self-presentation to the emergency department 21/28 (75% vs 25%),
      while solid tumours were self-referred to the emergency department 21/34 (62% vs
      38%) more often than via the GP. TTP and TTD were calculated for 87 patients.
      Wilms' tumour demonstrated the shortest median TTP of 7 days and TTD of 16 days.
      Lymphoma had the longest TTD, with TTP 107 days and TTD 120 days. Pathways to
      diagnosis via other specialties were longer. CONCLUSION: The majority of children
      diagnosed with cancer present via acute services, with the route varying between
      tumour types. Only two cases in 10 years were referred via the 2-week pathway,
      thus challenging its relevance in the paediatric population.

PMID- 26297701
TI  - Dose-and gender-specific effects of resistance training on circulating levels of
      brain derived neurotrophic factor (BDNF) in community-dwelling older adults.
AB  - BACKGROUND: BDNF is known to induce neuroplasticity and low circulating levels
      have been related to neuronal loss in older persons. Physical exercise is thought
      to trigger BDNF-induced neuroplasticity, but conflicting observations have been
      reported regarding the effects of resistance training on circulating BDNF in the
      elderly. These conflicting observations might reflect dose-and gender-specific
      differences. METHOD: Fifty-six apparently healthy elderly (68 +/- 5 years)
      participants were randomized to 12 weeks of resistance training (3*/week) at
      either high-resistance (HIGH, 8 Males, 10 Females, 2 * 10-15 repetitions at 80% 1
      RM), low-resistance (LOW, 9 Males, 10 Females, 1 * 80-100 repetitions at 20% 1
      RM), or mixed low-resistance (LOW+, 9 Males, 10 Females, 1 * 60 repetitions at
      20% 1 RM followed by 1 * 10-20 repetitions at 40% 1 RM). Serum was collected for
      BDNF assay at baseline and after 12 weeks (24 h-48 h after the last training).
      RESULTS: 12 weeks of LOW+ exercise significantly increased BDNF levels in male
      (from 34.9 +/- 10.7 ng/mL to 42.9 +/- 11.9 ng/mL, time * group interaction
      p=0.013), but not in female participants. No significant change was observed in
      HIGH or LOW, neither in male nor female subjects. CONCLUSION: Our results show
      that only the mixed-low-resistance training program with a very high number of
      repetitions at a sufficiently high external resistance was able to increase
      circulating BDNF in older male participants. Training to volitional fatigue might
      be necessary to obtain optimal results. Additional studies are needed to unravel
      the underlying mechanisms, as well as to confirm the observed gender difference.

PMID- 26297702
TI  - MIG1 Regulates Resistance of Candida albicans against the Fungistatic Effect of
      Weak Organic Acids.
AB  - Candida albicans is the leading cause of fungal infections; but it is also a
      member of the human microbiome, an ecosystem of thousands of microbial species
      potentially influencing the outcome of host-fungal interactions. Accordingly,
      antibacterial therapy raises the risk of candidiasis, yet the underlying
      mechanism is currently not fully understood. We hypothesize the existence of
      bacterial metabolites that normally control C. albicans growth and of fungal
      resistance mechanisms against these metabolites. Among the most abundant
      microbiota-derived metabolites found on human mucosal surfaces are weak organic
      acids (WOAs), such as acetic, propionic, butyric, and lactic acid. Here, we used
      quantitative growth assays to investigate the dose-dependent fungistatic
      properties of WOAs on C. albicans growth and found inhibition of growth to occur
      at physiologically relevant concentrations and pH values. This effect was
      conserved across distantly related fungal species both inside and outside the CTG
      clade. We next screened a library of transcription factor mutants and identified
      several genes required for the resistance of C. albicans to one or more WOAs. A
      single gene, MIG1, previously known for its role in glucose repression, conferred
      resistance against all four acids tested. Consistent with glucose being an
      upstream activator of Mig1p, the presence of this carbon source was required for
      WOA resistance in wild-type C. albicans. Conversely, a MIG1-complemented strain
      completely restored the glucose-dependent resistance against WOAs. We conclude
      that Mig1p plays a central role in orchestrating a transcriptional program to
      fight against the fungistatic effect of this class of highly abundant metabolites
      produced by the gastrointestinal tract microbiota. 

PMID- 26297703
TI  - Blood pressure reduction and control with fixed-dose combination
      perindopril/amlodipine: A Pan-Hellenic prospective observational study.
AB  - INTRODUCTION: Hypertension guidelines recommend fixed-dose combinations for
      enhanced blood pressure (BP) reduction and compliance. The objective of this
      study was to assess the effectiveness and safety of fixed-dose
      perindopril/amlodipine combination in reducing and controlling BP in Greek
      hypertensive patients, as well as the effect of baseline BP and added
      cardiovascular risk on BP reduction. METHODS: This 6-month prospective
      observational study included male or female patients ?18 years with essential
      hypertension prescribed fixed-dose combination perindopril/amlodipine. BP was
      measured at baseline and 3 and 6 months. Baseline cardiovascular risk and
      treatment compliance were also assessed. RESULTS: In 2231 per protocol patients,
      mean systolic BP decreased from 157.0+/-15.4 mm Hg to 129.0+/-7.9 mm Hg after 6
      months, and diastolic BP from 91.5+/-10.1 to 78.8+/-6.7 mm Hg (both p < 0.001).
      BP control was achieved in 84.8% at 6 months. Patients with higher baseline added
      cardiovascular risk or BP had greater BP reduction (p < 0.001). Compliance was
      good (97.1% took treatment "every day" or "quite often") and few (n = 27; 1.2%)
      discontinued treatment prematurely due to adverse events. CONCLUSIONS: Fixed-dose
      perindopril/amlodipine safely and effectively reduced high BP in real-life
      practice, achieving BP control in most patients. About half of Greek hypertensive
      patients have high/very high added cardiovascular risk.

PMID- 26297704
TI  - ACE polymorphisms and the acute response of blood pressure to a walk in medicated
      hypertensive patients.
AB  - HYPOTHESIS/INTRODUCTION: Polymorphisms of the angiotensin converting enzyme (ACE)
      gene can interfere with exercise-induced acute blood pressure (BP) reduction.
      This cross-over study investigated the acute effect of a single walk on BP and
      tested whether polymorphisms of the ACE gene might explain the variation in BP
      responses. MATERIALS AND METHODS: Thirty-four healthy medicated individuals were
      randomized to one control and one walking session at 60-75% of heart rate
      reserve. Subjects left the laboratory wearing an ambulatory BP monitor until
      waking the next morning. RESULTS: Overall, systolic BP was somewhat lower
      following the walking session (p=.06), which could be attributed to a
      consistently lower systolic BP for 5 h after exercise (p-interaction<.04)
      compared with control rest. Similarly, II/ID individuals had a lower systolic BP
      (p-interaction=.02) and diastolic BP (p-interaction<.01) for 5 h after walking
      compared with control rest. Among DD individuals, a single walk did not induce a
      reduction in BP (p-interaction>.05). CONCLUSIONS: Our results showed that
      postexercise hypotension can occur after a walk at moderate intensity in carriers
      of the I allele; we were not able to demonstrate this in DD individuals. Our
      results suggest that genetic variation in the ACE gene might affect the BP
      response to exercise, although more research is needed to confirm these findings.

PMID- 26297705
TI  - Inclusion of Small Indigenous Fish Improves Nutritional Quality During the First
      1000 Days.
AB  - BACKGROUND: Within food-based approaches to improve nutrition during the first
      1000 days of life, improved formulations of food products and the use of animal
      source foods, such as fish, are 2 widely cited strategies; however, there are few
      examples where the 2 strategies are combined. Furthermore, although small
      indigenous fish are highly nutritious and available to the poor in many regions
      of the world, their importance is often overlooked. OBJECTIVE: To document the
      development of 2 nutritious fish-based food products in Bangladesh: a chutney for
      pregnant and lactating women (PLW) and a complementary food (CF) for infants and
      young children (6-23 months), including potential contributions to recommended or
      desirable nutrient intakes in the first 1000 days, processing methods, and
      nutrient composition. METHODS: Local nutrient-rich ingredients and simple
      processing methods based on traditional knowledge (for the chutney), and a
      literature review (for the CF), were selected and trial batches produced.
      Products were analyzed for nutrient composition using standard analytical
      procedures and results compared with recommended or desirable nutrient intakes
      for women and children. RESULTS: Both products could contribute significantly to
      micronutrient intakes of PLW (24% of iron and 35% of calcium recommended intakes)
      and macro- and micronutrient intake of infants and young children (>= 65% of
      vitamin A, >= 61% of zinc, and 41% of iron desirable intakes) when consumed in
      the proposed serving size. CONCLUSION: Inclusion of small indigenous fish as an
      underutilized animal source food in combination with other local nutrient-rich
      ingredients in food products represents a promising food-based strategy to
      improve nutrition, with many additional potential benefits for communities
      involved in production, and therefore warrants further investigation.

PMID- 26297706
TI  - Examination of Age Variations in the Predictive Validity of Self-Rated Health.
AB  - OBJECTIVES: The high predictive validity of self-rated health (SRH) is a major
      strength of this widely used population health measure. Recent studies, however,
      noted that the predictive validity varies across population subgroups. The aim of
      this study is to examine respondents' age as a moderator of SRH predictive
      validity with respect to subsequent mortality risk. METHOD: Using data from the
      National Health Interview Survey-Linked Mortality Files (NHIS-LMF) 1986-2006, we
      estimate Cox proportional hazard models of all-cause and cause-specific mortality
      for adults aged 45-84 years as a function of their health ratings (N = 574,008).
      RESULTS: The data show significant age moderation of the predictive validity of
      SRH across all levels of ratings: the hazard ratios for mortality decline by
      about a half between the ages of 50 and 80 years. This attenuation appears
      primarily among earlier birth cohorts; there is no significant age attenuation in
      more recent cohorts-however, this may be in part attributed to the earlier ages
      when the respondents are observed. DISCUSSION: The findings of declining
      predictive validity of SRH across age imply that individuals may evaluate their
      health differently as they age. The results also suggest caution in using SRH to
      capture age-related health changes in the older population.

PMID- 26297708
TI  - Methodological Aspects of Subjective Life Expectancy: Effects of Culture-Specific
      Reporting Heterogeneity Among Older Adults in the United States.
AB  - OBJECTIVES: Subjective life expectancy (SLE) has been suggested as a predictor of
      mortality and mortality-related behaviors. Although critical for culturally
      diverse societies, these findings do not consider cross-cultural methodological
      comparability. Culture-specific reporting heterogeneity is a well-known
      phenomenon introducing biases, and research on this issue with SLE is not
      established. METHOD: Using data from the Health and Retirement Study, we examined
      reporting heterogeneity in SLE focusing on item nonresponse, focal points, and
      reports over time for five ethnic-cultural groups: non-Hispanic Whites, non
      Hispanic Blacks, non-Hispanic other races, English-interviewed Hispanics, and
      Spanish-interviewed Hispanics. RESULTS: On item nonresponse, Spanish-interviewed
      Hispanics said, "I don't know," to SLE significantly more than any other groups.
      Nearly half of the respondents chose 0, 50, or 100, making them focal points.
      However, the focal points differed: 50 for Whites, 100 for Blacks, and 0 for
      Spanish-interviewed Hispanics. The relationship of SLE measured at two time
      points was higher for Whites than minorities. Moreover, those who said "I don't
      know" to SLE showed higher subsequent mortality than those who gave an answer.
      SLE was not a significant mortality predictor for Hispanics. DISCUSSION: Overall,
      SLE is not free from culture-specific reporting heterogeneity. This warrants
      further research about its culture-relevant measurement mechanisms.

PMID- 26297709
TI  - Can Faith and Hospice Coexist: Is the African American Church the Key to
      Increased Hospice Utilization for African Americans?
AB  - African Americans are twice as likely as Caucasian Americans to choose aggressive
      hospital treatment when death is imminent. Repeat hospitalizations are traumatic
      for patients and drain patient and health system resources. Hospice care is a
      specialized alternative that vastly improves patient quality of life at end-of
      life. This study was conducted to determine if hospices partnering with African
      American churches to disseminate hospice education materials could increase
      utilization of hospice services by African Americans. Members of two African
      American churches (N = 34) participated in focus group discussions to elicit
      beliefs about hospice care. Focus group transcripts were coded and comments were
      grouped according to theme. Six themes were identified. Lack of knowledge about
      hospice services and spiritual beliefs emerged as the top two contributing
      factors for underutilization of hospice services. Study findings support
      partnerships between hospices and African American churches to provide hospice
      education to the African American community.

PMID- 26297707
TI  - Socioeconomic Predictors of the Employment of Migrant Care Workers by Italian
      Families Assisting Older Alzheimer's Disease Patients: Evidence From the Up-Tech
      Study.
AB  - BACKGROUND: The availability of family caregivers of older people is decreasing
      in Italy as the number of migrant care workers (MCWs) hired by families
      increases. There is little evidence on the influence of socioeconomic factors in
      the employment of MCWs. METHOD: We analyzed baseline data from 438 older people
      with moderate Alzheimer's disease (AD), and their family caregivers enrolled in
      the Up-Tech trial. We used bivariate analysis and multilevel regressions to
      investigate the association between independent variables-education, social
      class, and the availability of a care allowance-and three outcomes-employment of
      a MCW, hours of care provided by the primary family caregiver, and by the family
      network (primary and other family caregivers). RESULTS: The availability of a
      care allowance and the educational level were independently associated with
      employing MCWs. A significant interaction between education and care allowance
      was found, suggesting that more educated families are more likely to spend the
      care allowance to hire a MCW. DISCUSSION: Socioeconomic inequalities negatively
      influenced access both to private care and to care allowance, leading
      disadvantaged families to directly provide more assistance to AD patients. Care
      allowance entitlement needs to be reformed in Italy and in countries with similar
      long-term care and migration systems.

PMID- 26297710
TI  - Prognostic Significance of CD169+ Lymph Node Sinus Macrophages in Patients with
      Malignant Melanoma.
AB  - CD169 (sialoadhesin) is a sialic acid receptor that is specifically expressed on
      macrophages, including lymph node sinus macrophages. Animal studies suggest that
      CD169(+) macrophages in lymph nodes have properties in preventing cancers. In
      order to determine the significance of CD169(+) macrophages in patients with
      malignant melanoma, we evaluated tissue samples from 93 patients to investigate
      CD169 expression in regional lymph nodes (RLN) and determine the relationship of
      this expression with overall survival and various clinicopathologic factors.
      Higher densities of CD169(+) cells were significantly associated with longer
      overall survival (P = 0.001). A multivariate analysis showed that the density of
      CD169(+) cells was an independent prognostic factor, with higher densities
      correlating with higher density of CD8(+) cytotoxic T cells within tumor sites.
      High CD169 expression in macrophages could be stimulated by IFNalpha in vitro,
      and in RLNs, IFNalpha-producing macrophages and CD303(+) plasmacytoid dendritic
      cells were identified surrounding CD169(+) macrophages. These data suggest that
      IFNalpha-stimulated CD169(+) macrophages in RLNs are closely involved in T-cell
      mediated antitumor immunity and may be a useful marker for assessing the clinical
      prognosis and monitoring antitumor immunity in patients with malignant melanoma.

PMID- 26297711
TI  - Effector CD8+ T-cell Engraftment and Antitumor Immunity in Lymphodepleted Hosts
      Is IL7Ralpha Dependent.
AB  - Adoptive cellular therapy, in which activated tumor-reactive T cells are
      transferred into lymphodepleted recipients, is a promising cancer treatment
      option. Activation of T cells decreases IL7 responsiveness; therefore, IL15 is
      generally considered the main driver of effector T-cell responses in this
      setting. However, we found in lymphodepleted mice that CD8(+) T cells activated
      with IL12 showed enhanced engraftment that was initially dependent on host IL7,
      but not IL15. Mechanistically, enhanced IL7 responsiveness was conferred by
      elevated IL7Ralpha expression, which was critical for antitumor immunity.
      Elevated IL7Ralpha expression was achievable without IL12, as polyclonal CD8(+) T
      cells activated with high T-cell receptor (TCR) stimulation depended on T-cell
      IL7Ralpha expression and host IL7 for maximal engraftment. Finally, IL12
      conditioning during the activation of human CD8(+) T cells, including TCR
      modified T cells generated using a clinically relevant protocol, led to enhanced
      IL7Ralpha expression. Our results demonstrate the importance of the donor
      IL7Ralpha/host IL7 axis for effector CD8(+) T-cell engraftment and suggest novel
      strategies to improve adoptive cellular therapy as a cancer treatment.

PMID- 26297713
TI  - European Heart Rhythm Association/Heart Failure Association joint consensus
      document on arrhythmias in heart failure, endorsed by the Heart Rhythm Society
      and the Asia Pacific Heart Rhythm Society.

PMID- 26297712
TI  - HDAC Inhibition Upregulates PD-1 Ligands in Melanoma and Augments Immunotherapy
      with PD-1 Blockade.
AB  - Expression of PD-1 ligands by tumors and interaction with PD-1-expressing T cells
      in the tumor microenvironment can result in tolerance. Therapies targeting this
      coinhibitory axis have proven clinically successful in the treatment of
      metastatic melanoma, non-small cell lung cancer, and other malignancies.
      Therapeutic agents targeting the epigenetic regulatory family of histone
      deacetylases (HDAC) have shown clinical success in the treatment of some
      hematologic malignancies. Beyond direct tumor cell cytotoxicity, HDAC inhibitors
      have also been shown to alter the immunogenicity and enhance antitumor immune
      responses. Here, we show that class I HDAC inhibitors upregulated the expression
      of PD-L1 and, to a lesser degree, PD-L2 in melanomas. Evaluation of human and
      murine cell lines and patient tumors treated with a variety of HDAC inhibitors in
      vitro displayed upregulation of these ligands. This upregulation was robust and
      durable, with enhanced expression lasting past 96 hours. These results were
      validated in vivo in a B16F10 syngeneic murine model. Mechanistically, HDAC
      inhibitor treatment resulted in rapid upregulation of histone acetylation of the
      PD-L1 gene leading to enhanced and durable gene expression. The efficacy of
      combining HDAC inhibition with PD-1 blockade for treatment of melanoma was also
      explored in a murine B16F10 model. Mice receiving combination therapy had a
      slower tumor progression and increased survival compared with control and single
      agent treatments. These results highlight the ability of epigenetic modifiers to
      augment immunotherapies, providing a rationale for combining HDAC inhibitors with
      PD-1 blockade.

PMID- 26297715
TI  - The alpha and omega of galactosylceramides in T cell immune function.

PMID- 26297716
TI  - Structure-function analysis of the Drosophila melanogaster Caudal transcription
      factor provides insights into core promoter-preferential activation.

PMID- 26297714
TI  - Evidence-Based Diabetes Prevention and Control Programs and Policies in Local
      Health Departments.
AB  - PURPOSE: The purpose of this study is to: (1) assess implementation of evidence
      based programs and policies (EBPPs) related to diabetes prevention and control in
      local health departments, (2) assess feasibility of non-implemented diabetes
      prevention and control EBPPs, and (3) examine individual- and organizational
      level factors associated with implementation of diabetes prevention and control
      EBPPs. METHODS: An online survey was administered in January 2015 to key
      representatives of all local health departments in Missouri. Descriptive
      statistics were used to describe implementation and perceived feasibility of 20
      diabetes prevention and control EBPPs. Logistic regression was used to examine
      the association between individual and organizational factors and diabetes
      prevention and control EBPP implementation. RESULTS: One hundred local health
      departments participated (89% response rate) in the online survey. Most
      frequently implemented diabetes-related EBPPs in local health departments
      included: nutrition education for agency or community members, increased fruit
      and vegetable access in community settings, and community-wide campaigns to
      promote physical activity. Increased encouragement to others in the department to
      use evidence-based decision making and agency incentives to help employees use
      evidence-based decision making were positively associated with implementation of
      diabetes prevention and control EBPPs. CONCLUSIONS: Local health departments are
      on the "front line" of public health, and this study demonstrates the important
      role these organizations play in implementing diabetes prevention and control
      EBPPs. Potential leverage points for more widespread adoption of diabetes-related
      EBPPs in local health departments include education about and encouragement of
      evidence-based decision making and organizational incentives for employees to
      integrate evidence-based decision making into their diabetes prevention and
      control activities.

PMID- 26297717
TI  - Using of Group-Modeling in Predesign Phase of New Healthcare Environments:
      Stakeholders Experiences.
AB  - BACKGROUND: Current research shows a relationship between healthcare architecture
      and patient-related outcomes. The planning and designing of new healthcare
      environments is a complex process. The needs of the various end users of the
      environment must be considered, including the patients, the patients' significant
      others, and the staff. The aim of this study was to explore the experiences of
      healthcare professionals participating in group modeling utilizing system
      dynamics in the predesign phase of new healthcare environments. We engaged
      healthcare professionals in a series of workshops using system dynamics to
      discuss the planning of healthcare environments in the beginning of a
      construction and then interviewed them about their experience. METHODS: An
      explorative and qualitative design was used to describe participants' experiences
      of participating in the group-modeling projects. Participants (N = 20) were
      recruited from a larger intervention study using group modeling and system
      dynamics in planning and designing projects. The interviews were analyzed by
      qualitative content analysis. RESULTS: Two themes were formed, representing the
      experiences in the group-modeling process: "Participation in the group modeling
      generated knowledge and was empowering" and "Participation in the group modeling
      differed from what was expected and required the dedication of time and skills."
      CONCLUSIONS: The method can support participants in design teams to focus more on
      their healthcare organization, their care activities, and their aims rather than
      focusing on detailed layout solutions. This clarification is important when
      decisions about the design are discussed and prepared and will most likely lead
      to greater readiness for future building process.

PMID- 26297718
TI  - Affordance-Based Evaluations that Focus on Supporting the Needs of Users.

PMID- 26297719
TI  - An estimate of the proportion of symptomatic gonococcal, chlamydial and non
      gonococcal non-chlamydial urethritis attributable to oral sex among men who have
      sex with men: a case-control study.
AB  - BACKGROUND: Sexually transmitted infections (STIs) of the pharynx are common
      among men who have sex with men (MSM); the degree to which these infections are
      transmitted through oral sex is unknown. METHODS: We conducted a case-control
      study of MSM attending Public Health-Seattle & King County STD Clinic between
      2001 and 2013 to estimate the proportion of symptomatic urethritis cases
      attributable to oral sex using two methods. First, we categorised men into the
      following mutually exclusive behavioural categories based on their self-reported
      sexual history in the previous 60 days: (1) only received oral sex (IOS); (2)
      100% condom usage with insertive anal sex plus oral sex (PIAI); (3) inconsistent
      condom usage with anal sex (UIAI); and (4) no sex. We then determined the
      proportion of cases in which men reported the oropharynx as their only urethral
      exposure (IOS and PIAI). Second, we calculated the population attributable risk
      per cent (PAR%) associated with oral sex using Mantel-Haenszel OR estimates.
      RESULTS: Based on our behavioural categorisation method, men reported the
      oropharynx as their only urethral exposure in the past 60 days in 27.5% of
      gonococcal urethritis, 31.4% of chlamydial urethritis and 35.9% non-gonococcal,
      non-chlamydial urethritis (NGNCU) cases. The PAR%s for symptomatic gonococcal
      urethritis, chlamydial urethritis and NGNCU attributed to oropharyngeal exposure
      were 33.8%, 2.7% and 27.1%, respectively. CONCLUSIONS: The pharynx is an
      important source of gonococcal transmission, and may be important in the
      transmission of chlamydia and other, unidentified pathogens that cause
      urethritis. Efforts to increase pharyngeal gonorrhoea screening among MSM could
      diminish STI transmission.

PMID- 26297720
TI  - Predictors of provider recommendation for HPV vaccine among young adult men and
      women: findings from a cross-sectional survey.
AB  - BACKGROUND: Although physician recommendation is one of the strongest predictors
      of human papillomavirus (HPV) vaccination, it is unclear for whom physicians are
      recommending the vaccine. To help guide intervention efforts, this study
      investigated predictors of participant-reported physician recommendation for HPV
      vaccine among young adults in the USA. METHODS: Women and men (N=223) aged 18-26
      years were recruited online through Craigslist, a popular classified
      advertisements website. Ads were posted in the 25 largest US cities from
      September 2013 to March 2014. Participants completed a survey that assessed
      demographic and sociopolitical characteristics, sexual history, HPV vaccination
      history, and whether they had ever received a recommendation for HPV vaccine from
      a physician or healthcare provider. RESULTS: Fifty-three per cent reported
      receiving a recommendation for HPV vaccine and 45% had received >=1 dose of HPV
      vaccine. Participants who received a recommendation were over 35 times more
      likely to receive >=1 dose of HPV vaccine relative to participants without a
      recommendation. Bivariable and multivariable correlates of provider
      recommendation were identified. Results from the multivariable model indicated
      that younger (aged 18-21 years), female, White participants with health insurance
      (ie, employer-sponsored or some other type such as military-sponsored) were more
      likely to report receiving a recommendation for HPV vaccine. CONCLUSIONS: Results
      suggest that physician recommendation practices for HPV vaccination vary by
      characteristics of the patient. Findings underscore the key role of the
      healthcare provider in promoting HPV vaccination and have important implications
      for future HPV vaccine interventions with young adults.

PMID- 26297721
TI  - The HIV care continuum among men who have sex with men in Moscow, Russia: a cross
      sectional study of infection awareness and engagement in care.
AB  - OBJECTIVES: Early diagnosis and treatment of HIV infection is critical to
      improving clinical outcomes for HIV-infected individuals. We sought to
      characterise the HIV care continuum and identify correlates of being unaware of
      one's HIV infection among men who have sex with men (MSM) in Moscow, Russia.
      METHODS: Participants (N=1376) were recruited via respondent-driven sampling and
      completed a sociobehavioural survey and HIV testing from 2010 to 2013. Sample and
      population estimates were calculated for key steps along the HIV care continuum
      for HIV-infected MSM and logistic regression methods were used to examine
      correlates of being unaware of one's HIV infection. RESULTS: 15.6% (184/1177;
      population estimate: 11.6%; 95% CI 8.5% to 14.7%) of participants were HIV
      infected. Of these, only 23.4% (43/184; population estimate: 13.2; 95% CI 11.0 to
      15.4) were previously aware of their infection, 8.7% (16/184 population estimate:
      4.7; 95% CI 1.0 to 8.5) were on antiretroviral therapy (ART), and 4.4% (8/164;
      population estimate: 3.0; 95% CI 0.3 to 5.6) reported an undetectable viral load.
      Bisexual identity (reference: homosexual; adjusted odds ratio (AOR): 3.69; 95% CI
      1.19 to 11.43), having >=5 sexual partners in the last 6 months (reference: <=1;
      AOR: 4.23; 95% CI 1.17 to 15.28), and employer HIV testing requirements
      (reference: no; AOR: 15.43; 95% CI 1.62 to 147.01) were associated with being
      unaware of one's HIV infection. HIV testing in a specialised facility (reference:
      private; AOR: 0.06; 95% CI 0.01 to 0.53) and testing >=2 times in the last 12
      months (reference: none; AOR: 0.17; 95% CI 0.04 to 0.73) were inversely
      associated with being unaware of HIV infection. CONCLUSIONS: There is a steep
      gradient along the HIV care continuum for Moscow-based MSM beginning with low
      awareness of HIV infection. Efforts that improve access to acceptable HIV testing
      strategies, such as alternative testing facilities, and linkage to care are
      needed for key populations.

PMID- 26297722
TI  - Detrimental effects of introducing partial compulsory vaccination: experimental
      evidence.
AB  - BACKGROUND: During outbreaks of vaccine-preventable diseases, compulsory
      vaccination is sometimes discussed as a last resort to counter vaccine refusal.
      Besides ethical arguments, however, empirical evidence on the consequences of
      making selected vaccinations compulsory is lacking. Such evidence is needed to
      make informed public health decisions. This study therefore assesses the effect
      of partial compulsory vaccination on the uptake of other voluntary vaccines.
      METHOD: A total of 297 (N) participants took part in an online experiment that
      simulated two sequential vaccination decisions using an incentivized behavioural
      vaccination game. The game framework bases on epidemiological, psychological and
      game-theoretical models of vaccination. Participants were randomized to the
      compulsory vaccination intervention (n = 144) or voluntary vaccination control
      group (n = 153), which determined the decision architecture of the first of two
      decisions. The critical second decision was voluntary for all participants. We
      also assessed the level of anger, vaccination attitude and perceived severity of
      the two diseases. RESULTS: Compulsory vaccination increased the level of anger
      among individuals with a rather negative vaccination attitude, whereas voluntary
      vaccination did not. This led to a decrease in vaccination uptake by 39% in the
      second voluntary vaccination (reactance). CONCLUSION: Making only selected
      vaccinations compulsory can have detrimental effects on the vaccination programme
      by decreasing the uptake of voluntary vaccinations. As this effect occurred
      especially for vaccine hesitant participants, the prevalence of vaccine hesitancy
      within a society will influence the damage of partial compulsory vaccination.

PMID- 26297723
TI  - Bone wax to improvise a screw-holder: a makeshift emergency tool.
AB  - A missing screw-holder threatened cancellation of a case of facial trauma
      surgery. We present a simple makeshift tool using bone wax to improvise a
      temporary replacement for the screw-holder missing in our surgical instrument
      kit. This impromptu set-up is especially useful when operating in the field and
      faced with mass casualties. 

PMID- 26297724
TI  - The impact of intervening in green space in Dutch deprived neighbourhoods on
      physical activity and general health: results from the quasi-experimental URBAN40
      study.
AB  - BACKGROUND: Many problems concentrate in deprived neighbourhoods, among which is
      poor health. One possible way to address these health problems is to invest in
      the green space in deprived neighbourhoods. The number of evaluations of the
      public health impact of actual changes in neighbourhood green space is still
      limited. This study investigated the impact of real-life changes in the quality
      or quantity of green space in severely deprived neighbourhoods on physical
      activity and perceived general health. METHODS: Repeated cross-sectional surveys
      from 2004 till 2011 yielded self-reported information on leisure time walking,
      cycling and sports, and perceived general health of 48,132 adult residents. We
      fitted generalised mixed models to assess the rate of change per half year,
      estimate the linear trend, and the change in trends before and after the start of
      the urban regeneration mid-2008. Using a quasi-experimental design, we compared
      the trends in the intervention neighbourhoods with different selections of
      control areas. RESULTS: The deprived neighbourhoods that intervened in green
      space did not show more favourable changes in the trend of physical activity and
      good general health compared to all the different groups of control areas.
      CONCLUSIONS: We did not observe short-term positive effects on physical activity
      and general health among adults from improvements in green space in deprived
      neighbourhoods. This suggests that greening interventions that have been carried
      out in the context of the Dutch District Approach did not achieve short-term
      health gains among adults.

PMID- 26297725
TI  - Genetic Networks Required to Coordinate Chromosome Replication by DNA Polymerases
      alpha, delta, and epsilon in Saccharomyces cerevisiae.
AB  - Three major DNA polymerases replicate the linear eukaryotic chromosomes. DNA
      polymerase alpha-primase (Pol alpha) and DNA polymerase delta (Pol delta)
      replicate the lagging-strand and Pol alpha and DNA polymerase epsilon (Pol
      epsilon) the leading-strand. To identify factors affecting coordination of DNA
      replication, we have performed genome-wide quantitative fitness analyses of
      budding yeast cells containing defective polymerases. We combined temperature
      sensitive mutations affecting the three replicative polymerases, Pol alpha, Pol
      delta, and Pol epsilon with genome-wide collections of null and reduced function
      mutations. We identify large numbers of genetic interactions that inform about
      the roles that specific genes play to help Pol alpha, Pol delta, and Pol epsilon
      function. Surprisingly, the overlap between the genetic networks affecting the
      three DNA polymerases does not represent the majority of the genetic interactions
      identified. Instead our data support a model for division of labor between the
      different DNA polymerases during DNA replication. For example, our genetic
      interaction data are consistent with biochemical data showing that Pol epsilon is
      more important to the Pre-Loading complex than either Pol alpha or Pol delta. We
      also observed distinct patterns of genetic interactions between leading- and
      lagging-strand DNA polymerases, with particular genes being important for
      coupling proliferating cell nuclear antigen loading/unloading (Ctf18, Elg1) with
      nucleosome assembly (chromatin assembly factor 1, histone regulatory HIR
      complex). Overall our data reveal specialized genetic networks that affect
      different aspects of leading- and lagging-strand DNA replication. To help others
      to engage with these data we have generated two novel, interactive visualization
      tools, DIXY and Profilyzer. 

PMID- 26297726
TI  - Similar Efficacies of Selection Shape Mitochondrial and Nuclear Genes in Both
      Drosophila melanogaster and Homo sapiens.
AB  - Deleterious mutations contribute to polymorphism even when selection effectively
      prevents their fixation. The efficacy of selection in removing deleterious
      mitochondrial mutations from populations depends on the effective population size
      (Ne) of the mitochondrial DNA and the degree to which a lack of recombination
      magnifies the effects of linked selection. Using complete mitochondrial genomes
      from Drosophila melanogaster and nuclear data available from the same samples, we
      reexamine the hypothesis that nonrecombining animal mitochondrial DNA harbor an
      excess of deleterious polymorphisms relative to the nuclear genome. We find no
      evidence of recombination in the mitochondrial genome, and the much-reduced level
      of mitochondrial synonymous polymorphism relative to nuclear genes is consistent
      with a reduction in Ne. Nevertheless, we find that the neutrality index, a
      measure of the excess of nonsynonymous polymorphism relative to the neutral
      expectation, is only weakly significantly different between mitochondrial and
      nuclear loci. This difference is likely the result of the larger proportion of
      beneficial mutations in X-linked relative to autosomal loci, and we find little
      to no difference between mitochondrial and autosomal neutrality indices.
      Reanalysis of published data from Homo sapiens reveals a similar lack of a
      difference between the two genomes, although previous studies have suggested a
      strong difference in both species. Thus, despite a smaller Ne, mitochondrial loci
      of both flies and humans appear to experience similar efficacies of purifying
      selection as do loci in the recombining nuclear genome. 

PMID- 26297727
TI  - Appropriateness of endoscopic surveillance recommendations in organised
      colorectal cancer screening programmes based on the faecal immunochemical test.
AB  - OBJECTIVES: To assess the appropriateness of recommendations for endoscopic
      surveillance in organised colorectal cancer (CRC) screening programmes based on
      the faecal immunochemical test (FIT). DESIGN: 74 Italian CRC screening programmes
      provided aggregated data on the recommendations given after FIT-positive
      colonoscopies in 2011 and 2013. Index colonoscopies were divided into negative/no
      adenoma and low- risk, intermediate-risk and high-risk adenomas. Postcolonoscopy
      recommendations included a return to screening (FIT after 2 years or 5 years), an
      endoscopic surveillance after 6 months or after 1 year, 3 years or 5 years,
      surgery or other. We assessed the deviation from the postcolonoscopy
      recommendations of the European Guidelines in 2011 and 2013 and the correlation
      between overuse of endoscopic surveillance in 2011 and the process indicators
      associated with the endoscopic workload in 2013. RESULTS: 49 704 postcolonoscopy
      recommendations were analysed. High-risk, intermediate-risk and low-risk
      adenomas, and no adenomas were reported in 5.9%, 19.3%, 15.3% and 51.5% of the
      cases, respectively. Endoscopic surveillance was inappropriately recommended in
      67.4% and 7%, respectively, of cases with low-risk and no adenoma. Overall, 37%
      of all endoscopic surveillance recommendations were inappropriate (6696/17 860).
      Overuse of endoscopic surveillance was positively correlated with the extension
      of invitations (correlation coefficient (cc) 0.29; p value 0.03) and with
      compliance with post-FIT+ colonoscopy (cc 0.25; p value 0.05), while it was
      negatively correlated with total colonoscopy waiting times longer than 60 days
      (cc -0.26; p value 0.05). CONCLUSIONS: In organised screening programmes, a high
      rate of inappropriate recommendations for patients with low risk or no adenomas
      occurs, affecting the demand for endoscopic surveillance by a third.

PMID- 26297728
TI  - MR spectroscopy for assessing the effects of oxytocin on marrow adipogenesis
      induced by glucocorticoid in rabbits.
AB  - BACKGROUND: Previous studies suggest that oxytocin (OT) negatively modulates
      adipogenesis while promoting osteogenesis in vitro. Because of its effects on
      marrow stromal cells, OT might have potential utility in therapy for
      glucocorticoid-induced osteoporosis (GIO). PURPOSE: To explore the effects of OT
      on marrow adipogenesis in a rabbit model of GIO. MATERIAL AND METHODS: Thirty-six
      month-old female New Zealand rabbits were randomly assigned to the control, GIO,
      and GIO + OT groups. Magnetic resonance (MR) spectroscopy and multi-detector
      computed tomography (MDCT) were performed to detect marrow fat content (MFC) and
      bone mineral density (BMD) at baseline, and 1, 2, and 3 months. After 3 months of
      treatment, marrow adipocytes were quantitatively evaluated by histopathology.
      RESULTS: In the GIO group, MFC substantially increased from 34.1% to 43.2% at
      month 1, and it was maintained until month 3 (by 59.2%, all P <0.01). MFC values
      in the GIO group were significantly different from the control and OT-treated
      groups over time. Early OT treatment reversed marrow adiposity to levels of the
      controls. BMD values were significantly lower in the GIO group at months 2 and 3
      compared to the controls; however, partial recovery of vertebral BMD (87.1% of
      baseline) and femoral BMD (89.3% of baseline) in the OT-treated group were
      observed. The mean diameter and density of adipocyte and percentage of adipocyte
      area increased by 30.0%, 70.1%, and 88.9%, respectively (all P <0.05) in the GIO
      group, but remained unchanged in the OT-treated group. CONCLUSION: Early OT
      treatment was sufficient to eliminate glucocorticoid-induced marrow adiposity.

PMID- 26297729
TI  - Brain glucose metabolism in diffuse large B-cell lymphoma patients as assessed
      with FDG-PET: impact on outcome and chemotherapy effects.
AB  - BACKGROUND: There is a lack of data on the effect of rituximab, cyclophosphamide,
      doxorubicin, vincristine, and prednisone (R-CHOP) therapy on brain glucose
      metabolism of diffuse large B-cell lymphoma (DLBCL) patients, as measured by 18F
      fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). Moreover, the
      prognostic value of brain glucose metabolism measurements is currently unknown.
      PURPOSE: To investigate the use of FDG-PET for measurement of brain glucose
      metabolism in R-CHOP-treated DLBCL patients, and to assess its prognostic value.
      MATERIAL AND METHODS: This retrospective study included DLBCL patients who
      underwent FDG-PET including the brain. FDG-PET metabolic volume products (MVPs)
      of the entire brain, cerebral cortex, basal ganglia, and cerebellum were
      measured, before and after R-CHOP therapy. Whole-body total lesion glycolysis
      (TLG) was also measured. RESULTS: Thirty-eight patients were included, of whom 18
      had an appropriate end-of-treatment FDG-PET scan. There were no significant
      differences (P > 0.199) between pre- and post-treatment brain glucose metabolism
      metrics. Low basal ganglia MVP was associated with a significantly worse
      progression-free survival (PFS) and overall survival (OS) (P = 0.020 and P =
      0.032), and low cerebellar MVP was associated with a significantly worse OS (P =
      0.034). There were non-significant very weak correlations between pretreatment
      brain glucose metabolism metrics and TLG. In the multivariate Cox regression,
      only the National Comprehensive Cancer Network International Prognostic Index
      (NCCN-IPI) remained an independent predictor of PFS (hazard ratio 3.787, P =
      0.007) and OS (hazard ratio 2.903, P = 0.0345). CONCLUSION: Brain glucose
      metabolism was not affected by R-CHOP therapy. Low pretreatment brain glucose
      metabolism was associated with a worse outcome, but did not surpass the
      predictive value of the NCCN-IPI.

PMID- 26297730
TI  - Genetic and Morphological Characterization of Freshwater Shrimps (Caridina
      africana Kingsley, 1882) Reveals the Presence of Alien Shrimps in the Cape
      Floristic Region, South Africa.
AB  - Morphological identification and molecular data (mtDNA COI) were used to resolve
      the taxonomic identity of a non-native freshwater shrimp in the Cape Floristic
      Region (CFR) of South Africa and to evaluate levels of genetic diversity and
      differentiation in the species' core natural distribution. The species was
      morphologically and genetically identified as Caridina africana Kingsley, 1882,
      whose main natural distribution is in the KwaZulu-Natal (KZN) Province, more than
      1200 km from the point of new discovery. Subsequently, sequence data from natural
      populations occurring in seven rivers throughout KZN showed the presence of
      nuclear copies of the mtDNA COI gene (NUMTs) in 46 out of 140 individuals. Upon
      removal of sequences containing NUMTs, levels of genetic diversity were low in
      the alien population (possibly as a consequence of a bottleneck event), while
      varying levels of genetic diversity and differentiation were found in natural
      populations, indicating habitat heterogeneity, fragmentation and restricted gene
      flow between rivers. Following the present study, the alien shrimp has survived
      the Western Cape's winter and dispersed into a nearby tributary of the Eerste
      River System, hence posing an additional potential threat to endangered endemics.
      Understanding the biology of this alien species will aid detection and
      eradication procedures. 

PMID- 26297731
TI  - Plastic and Evolutionary Gene Expression Responses Are Correlated in European
      Grayling (Thymallus thymallus) Subpopulations Adapted to Different Thermal
      Environments.
AB  - Understanding how populations adapt to changing environmental conditions is a
      long-standing theme in evolutionary biology. Gene expression changes have been
      recognized as an important driver of local adaptation, but relatively little is
      known regarding the direction of change and in particular, about the interplay
      between plastic and evolutionary gene expression. We have previously shown that
      the gene expression profiles of European grayling (Thymallus thymallus)
      populations inhabiting different thermal environments include both plastic and
      evolutionary components. However, whether the plastic and evolutionary responses
      were in the same direction was not investigated in detail, nor was the identity
      of the specific genes involved. In this study, we show that the plastic changes
      in protein expression in response to different temperatures are highly correlated
      with the evolutionary response in grayling subpopulations adapted to different
      thermal environments. This finding provides preliminary evidence that the plastic
      response most likely facilitates adaptation during the early phases of
      colonization of thermal environments. The proteins that showed significant
      changes in expression level between warm and cold temperature treatments were
      mostly related to muscle development, which is consistent with earlier findings
      demonstrating muscle mass differentiation between cold and warm grayling
      populations.

PMID- 26297732
TI  - Intraorbital corticosteroid injection for the treatment of IgG4-related
      ophthalmic disease.
AB  - AIM: To review the efficacy of intraorbital corticosteroid injection for the
      treatment of IgG4-related ophthalmic disease (IgG4-ROD). METHODS: This study was
      a retrospective twin-centre histopathology review and observational case series.
      A chart review was undertaken for 10 cases of biopsy-confirmed IgG4-ROD treated
      with intraorbital corticosteroid injection. The main outcome measures were the
      magnitude, onset and duration of the clinical response. RESULTS: All cases
      received intraorbital injection(s) of 20 or 40 mg doses of triamcinolone
      acetonide suspension (Kenacort-A 40, Bristol-Myers Squibb, Australia).
      Intraorbital corticosteroid injection was associated with a swift positive
      response in all cases. 50% of cases achieved complete and sustained clinical
      remission during mean follow-up of 41 months. This was achieved with a single
      injection in three cases and with repeat injections in two cases. Peak clinical
      improvement was reached in <=7 days following 61% of injections. 60% of cases
      suffered relapse and 56% of relapses occurred during weeks 3 or 4 following
      injection. Sclerosing histology was associated with a clinical response that was
      gradual in onset (p=0.01) and that tended to be incomplete (p=0.4). There were no
      complications of injection other than brief discomfort. CONCLUSIONS: Intraorbital
      injection of corticosteroid may be a useful treatment option for IgG4-ROD. It may
      have a role as a first-line therapy in selected cases of IgG4-ROD centred in the
      anterior orbit. However, most cases require repeat injections due to incomplete
      response and relapse.

PMID- 26297733
TI  - Identification of P450 Oxidoreductase as a Major Determinant of Sensitivity to
      Hypoxia-Activated Prodrugs.
AB  - Hypoxia is a prevalent feature of many tumors contributing to disease progression
      and treatment resistance, and therefore constitutes an attractive therapeutic
      target. Several hypoxia-activated prodrugs (HAP) have been developed, including
      the phase III candidate TH-302 (evofosfamide) and the preclinical agent SN30000,
      which is an optimized analogue of the well-studied HAP tirapazamine. Experience
      with this therapeutic class highlights an urgent need to identify biomarkers of
      HAP sensitivity, including enzymes responsible for prodrug activation during
      hypoxia. Using genome-scale shRNA screens and a high-representation library
      enriched for oxidoreductases, we identified the flavoprotein P450 (cytochrome)
      oxidoreductase (POR) as the predominant determinant of sensitivity to SN30000 in
      three different genetic backgrounds. No other genes consistently modified SN30000
      sensitivity, even within a POR-negative background. Knockdown or genetic knockout
      of POR reduced SN30000 reductive metabolism and clonogenic cell death and
      similarly reduced sensitivity to TH-302 under hypoxia. A retrospective evaluation
      of head and neck squamous cell carcinomas showed heterogeneous POR expression and
      suggested a possible relationship between human papillomavirus status and HAP
      sensitivity. Taken together, our study identifies POR as a potential predictive
      biomarker of HAP sensitivity that should be explored during the clinical
      development of SN30000, TH-302, and other hypoxia-directed agents.

PMID- 26297734
TI  - The Estrogen Receptor Cofactor SPEN Functions as a Tumor Suppressor and Candidate
      Biomarker of Drug Responsiveness in Hormone-Dependent Breast Cancers.
AB  - The treatment of breast cancer has benefitted tremendously from the generation of
      estrogen receptor-alpha (ERalpha)-targeted therapies, but disease relapse
      continues to pose a challenge due to intrinsic or acquired drug resistance. In an
      effort to delineate potential predictive biomarkers of therapy responsiveness,
      multiple groups have identified several uncharacterized cofactors and interacting
      partners of ERalpha, including Split Ends (SPEN), a transcriptional corepressor.
      Here, we demonstrate a role for SPEN in ERalpha-expressing breast cancers. SPEN
      nonsense mutations were detectable in the ERalpha-expressing breast cancer cell
      line T47D and corresponded to undetectable protein levels. Further analysis of
      101 primary breast tumors revealed that 23% displayed loss of heterozygosity at
      the SPEN locus and that 3% to 4% harbored somatically acquired mutations. A
      combination of in vitro and in vivo functional assays with microarray-based
      pathway analyses showed that SPEN functions as a tumor suppressor to regulate
      cell proliferation, tumor growth, and survival. We also found that SPEN binds
      ERalpha in a ligand-independent manner and negatively regulates the transcription
      of ERalpha targets. Moreover, we demonstrate that SPEN overexpression sensitizes
      hormone receptor-positive breast cancer cells to the apoptotic effects of
      tamoxifen, but has no effect on responsiveness to fulvestrant. Consistent with
      these findings, two independent datasets revealed that high SPEN protein and RNA
      expression in ERalpha-positive breast tumors predicted favorable outcome in
      patients treated with tamoxifen alone. Together, our data suggest that SPEN is a
      novel tumor-suppressor gene that may be clinically useful as a predictive
      biomarker of tamoxifen response in ERalpha-positive breast cancers.

PMID- 26297735
TI  - Glioblastomas require integrin alphavbeta3/PAK4 signaling to escape senescence.
AB  - Integrin alphavbeta3 has been implicated as a driver of aggressive and metastatic
      disease, and is upregulated during glioblastoma progression. Here, we demonstrate
      that integrin alphavbeta3 allows glioblastoma cells to counteract senescence
      through a novel tissue-specific effector mechanism involving recruitment and
      activation of the cytoskeletal regulatory kinase PAK4. Mechanistically, targeting
      either alphavbeta3 or PAK4 led to emergence of a p21-dependent, p53-independent
      cell senescence phenotype. Notably, glioblastoma cells did not exhibit a similar
      requirement for either other integrins or additional PAK family members.
      Moreover, alphavbeta3/PAK4 dependence was not found to be critical in epithelial
      cancers. Taken together, our findings established that glioblastomas are
      selectively addicted to this pathway as a strategy to evade oncogene-induced
      senescence, with implications that inhibiting the alphavbeta3-PAK4 signaling axis
      may offer novel therapeutic opportunities to target this aggressive cancer.

PMID- 26297736
TI  - ADAPT, a Novel Scaffold Protein-Based Probe for Radionuclide Imaging of Molecular
      Targets That Are Expressed in Disseminated Cancers.
AB  - Small engineered scaffold proteins have attracted attention as probes for
      radionuclide-based molecular imaging. One class of these imaging probes, termed
      ABD-Derived Affinity Proteins (ADAPT), has been created using the albumin-binding
      domain (ABD) of streptococcal protein G as a stable protein scaffold. In this
      study, we report the development of a clinical lead probe termed ADAPT6 that
      binds HER2, an oncoprotein overexpressed in many breast cancers that serves as a
      theranostic biomarker for several approved targeting therapies. Surface-exposed
      amino acids of ABD were randomized to create a combinatorial library enabling
      selection of high-affinity binders to various proteins. Furthermore, ABD was
      engineered to enable rapid purification, to eradicate its binding to albumin, and
      to enable rapid blood clearance. Incorporation of a unique cysteine allowed site
      specific conjugation to a maleimido derivative of a DOTA chelator, enabling
      radionuclide labeling, 111In for SPECT imaging and 68Ga for PET imaging.
      Pharmacologic studies in mice demonstrated that the fully engineered molecule
      (111)In/68Ga-DOTA-(HE)3-ADAPT6 was specifically bound and taken up by HER2
      expressing tumors, with a high tumor-to-normal tissue ratio in xenograft models
      of human cancer. Unbound tracer underwent rapid renal clearance followed by high
      renal reabsorption. HER2-expressing xenografts were visualized by gamma-camera or
      PET at 1 hour after infusion. PET experiments demonstrated feasibility for
      discrimination of xenografts with high or low HER2 expression. Our results offer
      a preclinical proof of concept for the use of ADAPT probes for noninvasive in
      vivo imaging.

PMID- 26297737
TI  - Smoking, Diabetes Mellitus, Thyroid Dysfunction, and a Variety of Drugs Have
      Potential Effects on Serum HDL-C Level.

PMID- 26297738
TI  - B-cell precursor acute lymphoblastic leukemia cells use tunneling nanotubes to
      orchestrate their microenvironment.
AB  - Acute lymphoblastic leukemia (ALL) cells reside in the bone marrow
      microenvironment which nurtures and protects cells from chemotherapeutic drugs.
      The disruption of cell-cell communication within the leukemic niche may offer an
      important new therapeutic strategy. Tunneling nanotubes (TNTs) have been
      described as a novel mode of intercellular communication, but their presence and
      importance in the leukemic niche are currently unknown. Here, we show for the
      first time that primary B-cell precursor ALL (BCP-ALL) cells use TNTs to signal
      to primary mesenchymal stromal cells (MSCs). This signaling results in secretion
      of prosurvival cytokines, such as interferon-gamma-inducible protein 10/CXC
      chemokine ligand 10, interleukin 8, and monocyte chemotactic protein-1/CC
      chemokine ligand 2. A combination of TNT-disrupting conditions allows us to
      analyze the functional importance of TNTs in an ex vivo model. Our results
      indicate that TNT signaling is important for the viability of patient-derived B
      cell precursor ALL cells and induces stroma-mediated prednisolone resistance.
      Disruption of TNTs significantly inhibits these leukemogenic processes and
      resensitizes B-cell precursor ALL cells to prednisolone. Our findings establish
      TNTs as a novel communication mechanism by which ALL cells modulate their bone
      marrow microenvironment. The identification of TNT signaling in ALL-MSC
      communication gives insight into the pathobiology of ALL and opens new avenues to
      develop more effective therapies that interfere with the leukemic niche. 

PMID- 26297740
TI  - Enriching the drinking water of rats with extracts of Salvia officinalis and
      Thymus vulgaris increases their resistance to oxidative stress.
AB  - Nature is an attractive source of therapeutic compounds. In comparison to the
      artificial drugs, natural compounds cause less adverse side effects and are
      suitable for current molecularly oriented approaches to drug development and
      their mutual combining. Medicinal plants represent one of the most available
      remedy against various diseases. Proper examples are Salvia officinalis L. and
      Thymus vulgaris L. which are known aromatic medicinal plants. They are very
      popular and frequently used in many countries. The molecular mechanism of their
      biological activity has not yet been fully understood. The aim of this study was
      to ascertain if liver cells of experimental animals drinking extracts of sage or
      thyme will manifest increased resistance against oxidative stress. Adult Sprague
      Dawley rats were divided into seven groups. They drank sage or thyme extracts for
      2 weeks. At the end of the drinking period, blood samples were collected for
      determination of liver biochemical parameters and hepatocytes were isolated to
      analyze (i) oxidatively generated DNA damage (conventional and modified comet
      assay), (ii) activities of antioxidant enzymes [superoxide dismutase (SOD),
      glutathione peroxidase (GPx)] and (iii) content of glutathione. Intake of sage
      and thyme had no effect either on the basal level of DNA damage or on the
      activity of SOD in rat hepatocytes and did not change the biochemical parameters
      of blood plasma. Simultaneously, the activity of GPx was significantly increased
      and the level of DNA damage induced by oxidants was decreased. Moreover, sage
      extract was able to start up the antioxidant protection expressed by increased
      content of glutathione. Our results indicate that the consumption of
      S.officinalis and T.vulgaris extracts positively affects resistency of rat liver
      cells against oxidative stress and may have hepatoprotective potential.

PMID- 26297739
TI  - In vivo genome editing of the albumin locus as a platform for protein replacement
      therapy.
AB  - Site-specific genome editing provides a promising approach for achieving long
      term, stable therapeutic gene expression. Genome editing has been successfully
      applied in a variety of preclinical models, generally focused on targeting the
      diseased locus itself; however, limited targeting efficiency or insufficient
      expression from the endogenous promoter may impede the translation of these
      approaches, particularly if the desired editing event does not confer a selective
      growth advantage. Here we report a general strategy for liver-directed protein
      replacement therapies that addresses these issues: zinc finger nuclease (ZFN) 
      mediated site-specific integration of therapeutic transgenes within the albumin
      gene. By using adeno-associated viral (AAV) vector delivery in vivo, we achieved
      long-term expression of human factors VIII and IX (hFVIII and hFIX) in mouse
      models of hemophilia A and B at therapeutic levels. By using the same targeting
      reagents in wild-type mice, lysosomal enzymes were expressed that are deficient
      in Fabry and Gaucher diseases and in Hurler and Hunter syndromes. The
      establishment of a universal nuclease-based platform for secreted protein
      production would represent a critical advance in the development of safe,
      permanent, and functional cures for diverse genetic and nongenetic diseases. 

PMID- 26297741
TI  - The use of dose-response data in a margin of exposure approach to carcinogenic
      risk assessment for genotoxic chemicals in food.
AB  - Genotoxic substances are generally not permitted for deliberate use in food
      production. However, an appreciable number of known or suspected genotoxic
      substances occur unavoidably in food, e.g. from natural occurrence, environmental
      contamination and generation during cooking and processing. Over the past decade
      a margin of exposure (MOE) approach has increasingly been used in assessing the
      exposure to substances in food that are genotoxic and carcinogenic. The MOE is
      defined as a reference point on the dose-response curve (e.g. a benchmark dose
      lower confidences limit derived from a rodent carcinogenicity study) divided by
      the estimated human intake. A small MOE indicates a higher concern than a very
      large MOE. Whilst the MOE cannot be directly equated to risk, it supports
      prioritisation of substances for further research or for possible regulatory
      action, and provides a basis for communicating to the public. So far, the MOE
      approach has been confined to substances for which carcinogenicity data are
      available. In the absence of carcinogenicity data, evidence of genotoxicity is
      used only in hazard identification. The challenge to the genetic toxicology
      community is to develop approaches for characterising risk to human health based
      on data from genotoxicity studies. In order to achieve wide acceptance, it would
      be important to further address the issues that have been discussed in the
      context of dose-response modelling of carcinogenicity data in order to assign
      levels of concern to particular MOE values, and also whether it is possible to
      make generic conclusions on how potency in genotoxicity assays relates to
      carcinogenic potency.

PMID- 26297742
TI  - Death from ductal carcinoma in situ is very low except in young and black women,
      US data show.

PMID- 26297743
TI  - Data Sharing in Historical Perspective.

PMID- 26297744
TI  - Sharing Public Health Research Data: Toward the Development of Ethical Data
      Sharing Practice in Low- and Middle-Income Settings.
AB  - It is increasingly recognized that effective and appropriate data sharing
      requires the development of models of good data-sharing practice capable of
      taking seriously both the potential benefits to be gained and the importance of
      ensuring that the rights and interests of participants are respected and that
      risk of harms is minimized. Calls for the greater sharing of individual-level
      data from biomedical and public health research are receiving support among
      researchers and research funders. Despite its potential importance, data sharing
      presents important ethical, social, and institutional challenges in low-income
      settings. In this article, we report on qualitative research conducted in five
      low- and middle-income countries exploring the experiences of key research
      stakeholders and their views about what constitutes good data-sharing practice. 

PMID- 26297745
TI  - Views of Ethical Best Practices in Sharing Individual-Level Data From Medical and
      Public Health Research: A Systematic Scoping Review.
AB  - There is increasing support for sharing individual-level data generated by
      medical and public health research. This scoping review of empirical research and
      conceptual literature examined stakeholders' perspectives of ethical best
      practices in data sharing, particularly in low- and middle-income settings. Sixty
      nine empirical and conceptual articles were reviewed, of which, only five were
      empirical studies and eight were conceptual articles focusing on low- and middle
      income settings. We conclude that support for sharing individual-level data is
      contingent on the development and implementation of international and local
      policies and processes to support ethical best practices. Further conceptual and
      empirical research is needed to ensure data sharing policies and processes in low
      and middle-income settings are appropriately informed by stakeholders'
      perspectives. 

PMID- 26297746
TI  - Sweat, Skepticism, and Uncharted Territory: A Qualitative Study of Opinions on
      Data Sharing Among Public Health Researchers and Research Participants in Mumbai,
      India.
AB  - Efforts to internalize data sharing in research practice have been driven largely
      by developing international norms that have not incorporated opinions from
      researchers in low- and middle-income countries. We sought to identify the issues
      around ethical data sharing in the context of research involving women and
      children in urban India. We interviewed researchers, managers, and research
      participants associated with a Mumbai non-governmental organization, as well as
      researchers from other organizations and members of ethics committees. We
      conducted 22 individual semi-structured interviews and involved 44 research
      participants in focus group discussions. We used framework analysis to examine
      ideas about data and data sharing in general; its potential benefits or harms,
      barriers, obligations, and governance; and the requirements for consent. Both
      researchers and participants were generally in favor of data sharing, although
      limited experience amplified their reservations. We identified three themes:
      concerns that the work of data producers may not receive appropriate
      acknowledgment, skepticism about the process of sharing, and the fact that the
      terrain of data sharing was essentially uncharted and confusing. To increase data
      sharing in India, we need to provide guidelines, protocols, and examples of good
      practice in terms of consent, data preparation, screening of applications, and
      what individuals and organizations can expect in terms of validation,
      acknowledgment, and authorship. 

PMID- 26297747
TI  - Trust, Respect, and Reciprocity: Informing Culturally Appropriate Data-Sharing
      Practice in Vietnam.
AB  - International science funders and publishers are driving a growing trend in data
      sharing. There is mounting pressure on researchers in low- and middle-income
      settings to conform to new sharing policies, despite minimal empirically grounded
      accounts of the ethical challenges of implementing the policies in these
      settings. This study used in-depth interviews and focus group discussions with 48
      stakeholders in Vietnam to explore the experiences, attitudes, and expectations
      that inform ethical and effective approaches to sharing clinical research data.
      Distinct views on the role of trust, respect, and reciprocity were among those
      that emerged to inform culturally appropriate best practices. We conclude by
      discussing the challenges that authors of data-sharing policies should consider
      in this unique context. 

PMID- 26297748
TI  - Involving Research Stakeholders in Developing Policy on Sharing Public Health
      Research Data in Kenya: Views on Fair Process for Informed Consent, Access
      Oversight, and Community Engagement.
AB  - Increased global sharing of public health research data has potential to advance
      scientific progress but may present challenges to the interests of research
      stakeholders, particularly in low-to-middle income countries. Policies for data
      sharing should be responsive to public views, but there is little evidence of the
      systematic study of these from low-income countries. This qualitative study
      explored views on fair data-sharing processes among 60 stakeholders in Kenya with
      varying research experience, using a deliberative approach. Stakeholders'
      attitudes were informed by perceptions of benefit and concerns for research data
      sharing, including risks of stigmatization, loss of privacy, and undermining
      scientific careers and validity, reported in detail elsewhere. In this article,
      we discuss institutional trust-building processes seen as central to perceptions
      of fairness in sharing research data in this setting, including forms of
      community involvement, individual prior awareness and agreement to data sharing,
      independence and accountability of governance mechanisms, and operating under a
      national framework. 

PMID- 26297749
TI  - Perceived Benefits, Harms, and Views About How to Share Data Responsibly: A
      Qualitative Study of Experiences With and Attitudes Toward Data Sharing Among
      Research Staff and Community Representatives in Thailand.
AB  - The Thailand Major Overseas Programme coordinates large multi-center studies in
      tropical medicine and generates vast amounts of data. As the data sharing
      movement gains momentum, we wanted to understand attitudes and experiences of
      relevant stakeholders about what constitutes good data sharing practice. We
      conducted 15 interviews and three focus groups discussions involving 25
      participants and found that they generally saw data sharing as something
      positive. Data sharing was viewed as a means to contribute to scientific progress
      and lead to better quality analysis, better use of resources, greater
      accountability, and more outputs. However, there were also important reservations
      including potential harms to research participants, their communities, and the
      researchers themselves. Given these concerns, several areas for discussion were
      identified: data standardization, appropriate consent models, and governance. 

PMID- 26297750
TI  - Developing Ethical Practices for Public Health Research Data Sharing in South
      Africa: The Views and Experiences From a Diverse Sample of Research Stakeholders.
AB  - The abundance of South African clinical and public health research data has the
      potential to unlock important and valuable future advances in biomedical science.
      Amid increasing calls for more effective sharing of individual-level data,
      commitment to promote access to research data is evident within South Africa's
      public research sector, but national guidance and regulation are absent. This
      qualitative study examined the perceptions, experiences and concerns of 32
      research stakeholders about data-sharing practices. There was consensus about the
      utility of data sharing in publicly funded health research. However, disparate
      views emerged about the possible harms and benefits of sharing data and how these
      should be weighed. The relative dearth of policies governing data-sharing
      practices needs to be addressed and a framework of support developed that
      incentivizes data-sharing practices for researchers that are both ethical and
      effective. 

PMID- 26297752
TI  - Sharing Research Data to Improve Public Health: A Funder Perspective.
AB  - Through the Public Health Research Data Forum, global health research funders are
      working together to increase the availability of public health and epidemiology
      research data in ways that are equitable, ethical, and efficient. The Wellcome
      Trust funded the research reported in this special edition as a first step toward
      building an evidence base on the perspectives of research stakeholders in low-
      and middle-income countries on the benefits and challenges of sharing health
      research data. We hope this work will make a key contribution to discussions
      aimed at creating policy frameworks for data access at local, national, and
      regional levels that are sensitive to different contexts and ensure the benefits
      to research and health are realized in an equitable manner. 

PMID- 26297751
TI  - Best Practices for Ethical Sharing of Individual-Level Health Research Data From
      Low- and Middle-Income Settings.
AB  - Sharing individual-level data from clinical and public health research is
      increasingly being seen as a core requirement for effective and efficient
      biomedical research. This article discusses the results of a systematic review
      and multisite qualitative study of key stakeholders' perspectives on best
      practices in ethical data sharing in low- and middle-income settings. Our
      research suggests that for data sharing to be effective and sustainable, multiple
      social and ethical requirements need to be met. An effective model of data
      sharing will be one in which considered judgments will need to be made about how
      best to achieve scientific progress, minimize risks of harm, promote fairness and
      reciprocity, and build and sustain trust. 

PMID- 26297753
TI  - Addressing Global Data Sharing Challenges.
AB  - This issue of the Journal of Empirical Research on Human Research Ethics
      highlights the ethical issues that arise when researchers conducting projects in
      low- and middle-income countries seek to share the data they produce. Although
      sharing data is considered a best practice, the barriers to doing so are
      considerable and there is a need for guidance and examples. To that end, the
      authors of this article reviewed the articles in this special issue to identify
      challenges common to the five countries and to offer some practical advice to
      assist researchers in navigating this "uncharted territory," as some termed it.
      Concerns around informed consent, data management, data dissemination, and
      validation of research contributions were cited frequently as particularly
      challenging areas, so the authors focused on these four topics with the goal of
      providing specific resources to consult as well as examples of successful
      projects attempting to solve many of the problems raised. 

PMID- 26297754
TI  - The INDEPTH Data Repository: An International Resource for Longitudinal
      Population and Health Data From Health and Demographic Surveillance Systems.
AB  - The International Network for the Demographic Evaluation of Populations and Their
      Health (INDEPTH) is a global network of research centers that conduct
      longitudinal health and demographic evaluation of populations in low- and middle
      income countries (LMICs) currently in 52 health and demographic surveillance
      system (HDSS) field sites situated in sub-Saharan Africa (14 countries), Asia
      (India, Bangladesh, Thailand, Vietnam, and Indonesia), and Oceania (Papua New
      Guinea). Through this network of HDSS field sites, INDEPTH is capable of
      producing reliable longitudinal data about the lives of people in the research
      communities as well as how development policies and programs affect those lives.
      The aim of the INDEPTH Data Repository is to enable INDEPTH member centers and
      associated researchers to contribute and share fully documented, high-quality
      datasets with the scientific community and health policy makers. 

PMID- 26297755
TI  - Data Rights and Responsibilities: A Human Rights Perspective on Data Sharing.
AB  - A human-rights-based analysis can be a useful tool for the scientific community
      and policy makers as they develop codes of conduct, harmonized standards, and
      national policies for data sharing. The human rights framework provides a shared
      set of values and norms across borders, defines rights and responsibilities of
      various actors involved in data sharing, addresses the potential harms as well as
      the benefits of data sharing, and offers a framework for balancing competing
      values. The right to enjoy the benefits of scientific progress and its
      applications offers a particularly helpful lens through which to view data as
      both a tool of scientific inquiry to which access is vital and as a product of
      science from which everyone should benefit. 

PMID- 26297756
TI  - A Reflection on a Data Curation Journey.
AB  - This commentary is a reflection on experience of data preservation and sharing
      (i.e., data curation) practices developed in a South African research
      organization. The lessons learned from this journey have echoes in the findings
      and recommendations emerging from the present study in Low and Middle-Income
      Countries (LMIC) and may usefully contribute to more general reflection on the
      management of change in data practice. 

PMID- 26297757
TI  - The Transcription Factor Ehf Is Involved in TGF-beta-Induced Suppression of
      FcepsilonRI and c-Kit Expression and FcepsilonRI-Mediated Activation in Mast
      Cells.
AB  - FcepsilonRI, which is composed of alpha, beta, and gamma subunits, plays an
      important role in IgE-mediated allergic responses. TGF-beta1 has been reported to
      suppress FcepsilonRI and stem cell factor receptor c-Kit expression on mast cell
      surfaces and to suppress mast cell activation induced by cross-linking of
      FcepsilonRI. However, the molecular mechanism by which these expressions and
      activation are suppressed by TGF-beta1 remains unclear. In this study, we found
      that the expression of Ets homologous factor (Ehf), a member of the Ets family
      transcriptional factors, is upregulated by TGF-beta/Smad signaling in mouse bone
      marrow-derived mast cells (BMMCs). Forced expression of Ehf in BMMCs repressed
      the transcription of genes encoding FcepsilonRIalpha, FcepsilonRIbeta, and c-Kit,
      resulting in a reduction in cell surface FcepsilonRI and c-Kit expression.
      Additionally, forced expression of Ehf suppressed FcepsilonRI-mediated
      degranulation and cytokine production. Ehf inhibited the promoter activity of
      genes encoding FcepsilonRIalpha, FcepsilonRIbeta, and c-Kit by binding to these
      gene promoters. Furthermore, the mRNA levels of Gata1, Gata2, and Stat5b were
      lower in BMMCs stably expressing Ehf compared with control cells. Because GATA-1
      and GATA-2 are positive regulators of FcepsilonRI and c-Kit expression, decreased
      expression of GATAs may be also involved in the reduction of FcepsilonRI and c
      Kit expression. Decreased expression of Stat5 may contribute to the suppression
      of cytokine production by BMMCs. In part, mast cell response to TGF-beta1 was
      mimicked by forced expression of Ehf, suggesting that TGF-beta1 suppresses
      FcepsilonRI and c-Kit expression and suppresses FcepsilonRI-mediated activation
      through upregulation of Ehf. 

PMID- 26297758
TI  - Vaccination Produces CD4 T Cells with a Novel CD154-CD40-Dependent Cytolytic
      Mechanism.
AB  - The discovery of new vaccines against infectious diseases and cancer requires the
      development of novel adjuvants with well-defined activities. The TLR4 agonist
      adjuvant GLA-SE elicits robust Th1 responses to a variety of vaccine Ags and is
      in clinical development for both infectious diseases and cancer. We demonstrate
      that immunization with a recombinant protein Ag and GLA-SE also induces granzyme
      A expression in CD4 T cells and produces cytolytic cells that can be detected in
      vivo. Surprisingly, these in vivo CTLs were CD4 T cells, not CD8 T cells, and
      this cytolytic activity was not dependent on granzyme A/B or perforin. Unlike
      previously reported CD4 CTLs, the transcription factors Tbet and Eomes were not
      necessary for their development. CTL activity was also independent of the Fas
      ligand-Fas, TRAIL-DR5, and canonical death pathways, indicating a novel mechanism
      of CTL activity. Rather, the in vivo CD4 CTL activity induced by vaccination
      required T cell expression of CD154 (CD40L) and target cell expression of CD40.
      Thus, vaccination with a TLR4 agonist adjuvant induces CD4 CTLs, which kill
      through a previously unknown CD154-dependent mechanism. 

PMID- 26297759
TI  - Regulatory and Helper Follicular T Cells and Antibody Avidity to Simian
      Immunodeficiency Virus Glycoprotein 120.
AB  - T follicular regulatory cells (TFR) are a suppressive CD4(+) T cell subset that
      migrates to germinal centers (GC) during Ag presentation by upregulating the
      chemokine receptor CXCR5. In the GC, TFR control T follicular helper cell (TFH)
      expansion and modulate the development of high-affinity Ag-specific responses. In
      this study, we identified and characterized TFR as CXCR5(+)CCR7(-) "follicular" T
      regulatory cells in lymphoid tissues of healthy rhesus macaques, and we studied
      their dynamics throughout infection in a well-defined animal model of HIV
      pathogenesis. TFR were infected by SIVmac251 and had comparable levels of SIV DNA
      to CXCR5(-)CCR7(+) "T zone" T regulatory cells and TFH. Contrary to the SIV
      associated TFH expansion in the chronic phase of infection, we observed an
      apparent reduction of TFR frequency in cell suspension, as well as a decrease of
      CD3(+)Foxp3(+) cells in the GC of intact lymph nodes. TFR frequency was inversely
      associated with the percentage of TFH and, interestingly, with the avidity of the
      Abs that recognize the SIV gp120 envelope protein. Our findings show changes in
      the TFH/TFR ratio during chronic infection and suggest possible mechanisms for
      the unchecked expansion of TFH cells in HIV/SIV infection. 

PMID- 26297760
TI  - Macrophages and Myeloid Dendritic Cells Lose T Cell-Stimulating Function in
      Simian Immunodeficiency Virus Infection Associated with Diminished IL-12 and IFN
      alpha Production.
AB  - Impaired T cell responses are a defining characteristic of HIV infection, but the
      extent to which altered mononuclear phagocyte function contributes to this defect
      is unclear. We show that mononuclear phagocytes enriched from rhesus macaque
      lymph nodes have suppressed ability to stimulate CD4 T cell proliferation and IFN
      gamma release after acute SIV infection. When individual populations were
      isolated, myeloid dendritic cells (mDC) and macrophages but not plasmacytoid DC
      (pDC) had suppressed capacity to stimulate CD4 T cell proliferation, with
      macrophage function declining as infection progressed. Macrophages, but not pDC
      or mDC, had suppressed capacity to induce IFN-gamma release from CD4 T cells in
      acute infection, even after stimulation with virus-encoded TLR7/8 ligand. Changes
      in expression of costimulatory molecules did not explain loss of function
      postinfection. Conversely, pDC and mDC had marked loss of IFN-alpha and IL-12
      production, respectively, and macrophages lost production of both cytokines. In T
      cell cocultures without TLR7/8 ligand, macrophages were the primary source of IL
      12, which was profoundly suppressed postinfection and correlated with loss of IFN
      gamma release by T cells. TLR7/8-stimulated pDC, mDC and macrophages all produced
      IL-12 in T cell cocultures, which was suppressed in chronic infection.
      Supplementing IL-12 enhanced mDC-driven IFN-gamma release from T cells, and IL-12
      and IFN-alpha together restored function in TLR7/8-activated macrophages. These
      findings reveal loss of macrophage and mDC T cell-stimulating function in lymph
      nodes of SIV-infected rhesus macaques associated with diminished IL-12 and IFN
      alpha production that may be a factor in AIDS immunopathogenesis. 

PMID- 26297761
TI  - Plasmacytoid Dendritic Cell Activation and IFN-alpha Production Are Prominent
      Features of Murine Autoimmune Pancreatitis and Human IgG4-Related Autoimmune
      Pancreatitis.
AB  - The abnormal immune response accompanying IgG4-related autoimmune pancreatitis
      (AIP) is presently unclear. In this study, we examined the role of plasmacytoid
      dendritic cell (pDC) activation and IFN-alpha production in this disease as well
      as in a murine model of AIP (MRL/Mp mice treated with polyinosinic-polycytidylic
      acid). We found that the development of AIP in treated MRL/Mp mice occurred in
      parallel with pancreatic accumulation of pDCs producing IFN-alpha, and with pDC
      depletion and IFN-alpha-blocking studies, we showed that such accumulation was
      necessary for AIP induction. In addition, we found that the pancreas of treated
      MRL/Mp mice contained neutrophil extracellular traps (NETs) shown previously to
      stimulate pDCs to produce IFN-alpha. Consistent with these findings, we found
      that patients with IgG4-related AIP also exhibited pancreatic tissue localization
      of IFN-alpha-expressing pDCs and had significantly higher serum IFN-alpha levels
      than healthy controls. In addition, the inflamed pancreas of these patients but
      not controls also contained NETs that were shown to be capable of pDC activation.
      More importantly, patient pDCs cultured in the presence of NETs produced greatly
      increased levels of IFN-alpha and induced control B cells to produce IgG4 (but
      not IgG1) as compared with control pDCs. These data suggest that pDC activation
      and production of IFN-alpha is a major cause of murine AIP; in addition, the
      increased pDC production of IFN-alpha and its relation to IgG4 production
      observed in IgG4-related AIP suggest that this mechanism also plays a role in the
      human disease. 

PMID- 26297762
TI  - The Neurorepellent Slit2 Inhibits Postadhesion Stabilization of Monocytes
      Tethered to Vascular Endothelial Cells.
AB  - The secreted neurorepellent Slit2, acting through its transmembrane receptor,
      Roundabout (Robo)-1, inhibits chemotaxis of varied cell types, including
      leukocytes, endothelial cells, and vascular smooth muscle cells, toward diverse
      attractants. The role of Slit2 in regulating the steps involved in recruitment of
      monocytes in vascular inflammation is not well understood. In this study, we
      showed that Slit2 inhibited adhesion of monocytic cells to activated human
      endothelial cells, as well as to immobilized ICAM-1 and VCAM-1. Microfluidic live
      cell imaging showed that Slit2 inhibited the ability of monocytes tethered to
      endothelial cells to stabilize their actin-associated anchors and to resist
      detachment in response to increasing shear forces. Transfection of constitutively
      active plasmids revealed that Slit2 inhibited postadhesion stabilization of
      monocytes on endothelial cells by preventing activation of Rac1. We further found
      that Slit2 inhibited chemotaxis of monocytes toward CXCL12 and CCL2. To determine
      whether Slit2 and Robo-1 modulate pathologic monocyte recruitment associated with
      vascular inflammation and cardiovascular disease, we tested PBMC from patients
      with coronary artery disease. PBMC from these patients had reduced surface levels
      of Robo-1 compared with healthy age- and sex-matched subjects, and Slit2 failed
      to inhibit chemotaxis of PBMC of affected patients, but not healthy control
      subjects, toward CCL2. Furthermore, administration of Slit2 to atherosclerosis
      prone LDL receptor-deficient mice inhibited monocyte recruitment to nascent
      atherosclerotic lesions. These results demonstrate that Slit2 inhibits chemotaxis
      of monocytes, as well as their ability to stabilize adhesions and resist
      detachment forces. Slit2 may represent a powerful new tool to inhibit pathologic
      monocyte recruitment in vascular inflammation and atherosclerosis. 

PMID- 26297763
TI  - IL-9 Expression by Invariant NKT Cells Is Not Imprinted during Thymic
      Development.
AB  - Invariant NKT (iNKT) cell thymic development can lead to distinct committed
      effector lineages, namely NKT1, NKT2, and NKT17. However, following
      identification of IL-9-producing iNKT cells involved in mucosal inflammation,
      their development remains unaddressed. In this study, we report that although
      thymic iNKT cells from naive mice do not express IL-9, iNKT cell activation in
      the presence of TGF-beta and IL-4 induces IL-9 secretion in murine and human iNKT
      cells. Acquisition of IL-9 production was observed in different iNKT subsets
      defined by CD4, NK1.1, and neuropilin-1, indicating that distinct functional
      subpopulations are receptive to IL-9 polarization. Transcription factor
      expression kinetics suggest that regulatory mechanisms of IL-9 expression are
      shared by iNKT and CD4 T cells, with Irf4 and Batf deficiency deeply affecting IL
      9 production. Importantly, adoptive transfer of an enriched IL-9(+) iNKT cell
      population leads to exacerbated allergic inflammation in the airways upon
      intranasal immunization with house dust mite, confirming the ability of IL-9
      producing iNKT cells to mediate proinflammatory effects in vivo, as previously
      reported. Taken together, our data show that peripheral iNKT cells retain the
      capacity of shaping their function in response to environmental cues, namely TGF
      beta and IL-4, adopting an IL-9-producing NKT cell phenotype able to mediate
      proinflammatory effects in vivo, namely granulocyte and mast cell recruitment to
      the lungs. 

PMID- 26297764
TI  - Decreased T Follicular Regulatory Cell/T Follicular Helper Cell (TFH) in Simian
      Immunodeficiency Virus-Infected Rhesus Macaques May Contribute to Accumulation of
      TFH in Chronic Infection.
AB  - T follicular helper cells (TFH) are critical for the development and maintenance
      of germinal center (GC) and humoral immune responses. During chronic HIV/SIV
      infection, TFH accumulate, possibly as a result of Ag persistence. The HIV/SIV
      associated TFH expansion may also reflect lack of regulation by suppressive
      follicular regulatory CD4(+) T cells (TFR). TFR are natural regulatory T cells
      (TREG) that migrate into the follicle and, similar to TFH, upregulate CXCR5, Bcl
      6, and PD1. In this study, we identified TFR as
      CD4(+)CD25(+)FOXP3(+)CXCR5(+)PD1(hi)Bcl-6(+) within lymph nodes of rhesus
      macaques (RM) and confirmed their localization within the GC by
      immunohistochemistry. RNA sequencing showed that TFR exhibit a distinct
      transcriptional profile with shared features of both TFH and TREG, including
      intermediate expression of FOXP3, Bcl-6, PRDM1, IL-10, and IL-21. In healthy, SIV
      uninfected RM, we observed a negative correlation between frequencies of TFR and
      both TFH and GC B cells, as well as levels of CD4(+) T cell proliferation. Post
      SIV infection, the TFR/TFH ratio was reduced with no change in the frequency of
      TREG or TFR within the total CD4(+) T cell pool. Finally, we examined whether
      higher levels of direct virus infection of TFR were responsible for their
      relative depletion post SIV infection. We found that TFH, TFR, and TREG sorted
      from SIV-infected RM harbor comparable levels of cell-associated viral DNA. Our
      data suggest that TFR may contribute to the regulation and proliferation of TFH
      and GC B cells in vivo and that a decreased TFR/TFH ratio in chronic SIV
      infection may lead to unchecked expansion of both TFH and GC B cells. 

PMID- 26297765
TI  - Human Mucosa-Associated Invariant T Cells Accumulate in Colon Adenocarcinomas but
      Produce Reduced Amounts of IFN-gamma.
AB  - Mucosa-associated invariant T (MAIT) cells are innate-like T cells with a
      conserved TCR alpha-chain recognizing bacterial metabolites presented on the
      invariant MHC-related 1 molecule. MAIT cells are present in intestinal tissues
      and liver, and they rapidly secrete IFN-gamma and IL-17 in response to bacterial
      insult. In colon cancer, IL-17-driven inflammation promotes tumor progression,
      whereas IFN-gamma production is essential for antitumor immunity. Thus, tumor
      associated MAIT cells may affect antitumor immune responses by their secreted
      cytokines. However, the knowledge of MAIT cell presence and function in tumors is
      virtually absent. In this study, we determined the frequency, phenotype, and
      functional capacity of MAIT cells in colon adenocarcinomas and unaffected colon
      lamina propria. Flow cytometric analyses showed significant accumulation of MAIT
      cells in tumor tissue, irrespective of tumor stage or localization. Colonic MAIT
      cells displayed an activated memory phenotype and expression of chemokine
      receptors CCR6 and CCR9. Most MAIT cells in unaffected colon tissues produced IFN
      gamma, whereas only few produced IL-17. Colonic MAIT cells also produced TNF
      alpha, IL-2, and granzyme B. In the tumors, significantly lower frequencies of
      IFN-gamma-producing MAIT cells were seen, whereas there were no differences in
      the other cytokines analyzed, and in vitro studies showed that secreted factors
      from tumor tissue reduced IFN-gamma production from MAIT cells. In conclusion,
      MAIT cells infiltrate colon tumors but their ability to produce IFN-gamma is
      substantially reduced. We suggest that MAIT cells have the capacity to promote
      local immune responses to tumors, but factors in the tumor microenvironment act
      to reduce MAIT cell IFN-gamma production. 

PMID- 26297766
TI  - An unusual case of sepsis? A rare presentation of a common disease.

PMID- 26297767
TI  - Consequences of low birth weight, maternal illiteracy and poor access to medical
      care in rural India: infantile iatrogenic Cushing syndrome.
AB  - Home delivery, low birth weight babies and maternal illiteracy among the poor in
      rural India are frequent. The rural poor prefer to seek healthcare from private
      providers, most of whom have no formal medical training and buy medicines from
      private pharmacies without a prescription owing to a weakly regulated
      environment. This report is of a 4-month-old baby from a remote village in
      northern India, who presented with exogenous Cushing syndrome. This baby was a
      full-term low birth weight home delivery. As the baby was not growing well,
      treatment was started at 1 month by a private doctor with betamethasone drops The
      mother on her own volition continued giving the betamethasone drops by buying the
      medicine over the counter from a private pharmacy. This case highlights the gaps
      in essential health services in rural India and the steps being taken to improve
      the situation.

PMID- 26297768
TI  - Glandular odontogenic cyst: a rare entity revealed and a review of the
      literature.
AB  - A glandular odontogenic cyst (GOC) is a developmental cyst that is a clinically
      rare and histopathologically unusual type of odontogenic cyst. GOCs are now
      relatively well-known entities; their importance relates to the fact that they
      exhibit a propensity for recurrence rates from 21% to 55%, similar to odontogenic
      keratocysts, and may be confused microscopically with central mucoepidermoid
      carcinoma. Furthermore, some microscopic features of GOCs may also be found in
      dentigerous, botryoid, radicular and surgical ciliated cysts. The present case
      report aims to describe a typical case of GOC, throwing light on its epidemiology
      and origin, as well as on its clinical, radiographic and microscopic features,
      which may be helpful for diagnosis in problematic cases, long-term follow-up and
      to determine the most appropriate treatment. 

PMID- 26297769
TI  - Gorlin-Goltz syndrome in twin brothers: an unusual occurrence with review of the
      literature.
AB  - Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome, is
      caused by genetic alteration produced by a mutation in the 'patched' tumour
      suppressor gene, and is inherited in a dominant autosomal way. Although sporadic
      cases have been found, this syndrome has rarely been reported in twin patients.
      The syndrome is characterised by a wide range of developmental abnormalities and
      has a predisposition to neoplasms such as multiple pigmented basal cell
      carcinomas and keratocysts in jaws; it also has other features such as palmar
      and/or plantar pits and calcification of falx cerebri. Owing to the critical oral
      and maxillofacial manifestations of this syndrome, it is important to recognise
      its characteristics in order to make a diagnosis, and to plot early preventive
      treatment and establish the right genetic evidence. Based on a combination of
      imaging, clinical and histopathological findings, we present a diagnosed case of
      Gorlin-Goltz syndrome in 18-year-old twin brothers. All cystic lesions were
      enucleated and 1 year follow-up showed no recurrence.

PMID- 26297770
TI  - Haemodynamic changes due to systemic arterial shunts in a destroyed lung
      mimicking pulmonary thromboembolism on CT.

PMID- 26297771
TI  - Juxtacortical haemorrhage in cerebral venous sinus thrombosis: 'The Cashew Nut
      Sign'.

PMID- 26297772
TI  - An unusual cause of abdominal pain in a middle-aged man.

PMID- 26297773
TI  - Medulloblastoma with myogenic differentiation: a rare medulloblastoma variant in
      a young child.

PMID- 26297774
TI  - Four new species of Phylloporia (Hymenochaetales, Basidiomycota) from tropical
      China with a key to Phylloporia species worldwide.
AB  - Phylloporia (Hymenochaetaceae) is a monophyletic and cosmopolitan genus with
      diverse morphology. In a nuc 28S rDNA-based phylogeny specimens collected from
      tropical China were recovered as four new lineages within the Phylloporia clade.
      Based on morphological evidence and host relationships, these four lineages are
      described and illustrated as four new species: Phylloporia clausenae, P.
      cylindrispora, P. flacourtiae and P. homocarnica. The distinctive morphological
      characters of the four new species of Phylloporia are discussed. In addition, the
      phylogenetic position of P. tiliae, which was recently described from China, was
      confirmed in the Phylloporia clade. A key is provided for all 30 accepted species
      of Phylloporia. 

PMID- 26297775
TI  - Wood-inhabiting fungi in southern Italy forest stands: morphogroups, vegetation
      types and decay classes.
AB  - The authors conducted an ecological study of forests subjected to varying
      management. The aim of the study was to extend and integrate, within a
      multivariate context, knowledge of how saproxylic fungal communities behave along
      altitudinal/vegetational gradients in response to the varying features and
      quality of coarse woody debris (CWD). The intra-annual seasonal monitoring of
      saproxylic fungi, based on sporocarp inventories, was used to investigate
      saproxylic fungi in relation to vegetation types and management categories. We
      analyzed fungal species occurrence, recorded according to the presence/absence
      and frequency of sporocarps, on the basis of the harvest season, of coarse woody
      debris decay classes as well as other environmental and ecological variables. Two
      way cluster analysis, DCA and Spearman's rank correlations, for indirect gradient
      analysis, were performed to identify any patterns of seasonality and decay. Most
      of the species were found on CWD in an intermediate decay stage. The first DCA
      axis revealed the vegetational/microclimate gradient as the main driver of fungal
      community composition, while the second axis corresponded to a strong gradient of
      CWD decay classes. 

PMID- 26297776
TI  - Root-associated fungal community response to drought-associated changes in
      vegetation community.
AB  - Recent droughts in southwestern USA have led to large-scale mortality of pinon
      (Pinus edulis) in pinon-juniper woodlands. Pinon mortality alters soil moisture,
      nutrient and carbon availability, which could affect the root-associated fungal
      (RAF) communities and therefore the fitness of the remaining plants. We collected
      fine root samples at a pinon-juniper woodland and a juniper savannah site in
      central New Mexico. Roots were collected from pinon and juniper (Juniperus
      monosperma) trees whose nearest neighbors were live pinon, live juniper or dead
      pinon. RAF communities were analyzed by 454 pyrosequencing of the universal
      fungal ITS region. The most common taxa were Hypocreales and Chaetothyriales.
      More than 10% of ITS sequences could not be assigned taxonomy at the phylum
      level. Two of the unclassified OTUs significantly differed between savanna and
      woodland, had few like sequences in GenBank and formed new fungal clades with
      other unclassified RAF from arid plants, highlighting how little study has been
      done on the RAF of arid ecosystems. Plant host or neighbor did not affect RAF
      community composition. However, there was a significant difference between RAF
      communities from woodland vs. savanna, indicating that abiotic factors such as
      temperature and aridity might be more important in structuring these RAF
      communities than biotic factors such as plant host or neighbor identity.
      Ectomycorrhizal fungi (EM) were present in juniper as well as pinon in the
      woodland site, in contrast with previous research, but did not occur in juniper
      savanna, suggesting a potential shared EM network with juniper. RAF richness was
      lower in hosts that were neighbors of the opposite host. This may indicate
      competitive exclusion between fungi from different hosts. Characterizing these
      communities and their responses to environment and plant neighborhood is a step
      toward understanding the effects of drought on a biome that spans 19,000,000 ha
      of southwestern USA.

PMID- 26297777
TI  - Disentangling the complex of Lichenothelia species from rock communities in the
      desert.
AB  - Rock-inhabiting fungi (RIF) are melanized, meristematic fungi which dwell on and
      within rocks and have adapted to withstand harsh conditions in extreme habitats
      worldwide. Their morphological and genetic diversity remained unknown for a long
      time, but in the past few years culture-dependent and molecular phylogenetic
      approaches have contributed to uncovering the species richness of these otherwise
      very inconspicuous fungi. Only a few taxa of RIF develop both sexual reproductive
      structure (fertile stromata and/or pycnidia) and show multiple life styles,
      interacting with algae and lichen thalli in different ways. The genus
      Lichenothelia is one of these: It is characterized by fertile stromata and
      pycnidia and by species which can grow on and within exposed rocks, optionally
      associating with algae, with some species also being lichenicolous. The genus
      Lichenothelia includes up to now 25 species and form a monotypic family
      (Lichenotheliaceae) and order (Lichenotheliales) in Dothideomycetes. Here we
      focused on a group of Lichenothelia taxa distributed in the hot arid region of
      the Sonoran and Mojave Deserts in the Joshua Tree National Park in California. We
      performed molecular and morphological analyses and culture isolation and
      considered the ecology of the environmental samples to disentangle five species.
      We present the revision of two species already described, Lichenothelia calcarea
      and L. convexa, and introduce three new taxa to science, L. arida, L. umbrophila
      and L. umbrophila var. pullata. 

PMID- 26297778
TI  - A survey of genes encoding H2O2-producing GMC oxidoreductases in 10 Polyporales
      genomes.
AB  - The genomes of three representative Polyporales (Bjerkandera adusta, Phlebia
      brevispora and a member of the Ganoderma lucidum complex) recently were sequenced
      to expand our knowledge on the diversity and distribution of genes involved in
      degradation of plant polymers in this Basidiomycota order, which includes most
      wood-rotting fungi. Oxidases, including members of the glucose-methanol-choline
      (GMC) oxidoreductase superfamily, play a central role in the above degradative
      process because they generate extracellular H2O2 acting as the ultimate oxidizer
      in both white-rot and brown-rot decay. The survey was completed by analyzing the
      GMC genes in the available genomes of seven more species to cover the four
      Polyporales clades. First, an in silico search for sequences encoding members of
      the aryl-alcohol oxidase, glucose oxidase, methanol oxidase, pyranose oxidase,
      cellobiose dehydrogenase and pyranose dehydrogenase families was performed. The
      curated sequences were subjected to an analysis of their evolutionary
      relationships, followed by estimation of gene duplication/reduction history
      during fungal evolution. Second, the molecular structures of the near one hundred
      GMC oxidoreductases identified were modeled to gain insight into their structural
      variation and expected catalytic properties. In contrast to ligninolytic
      peroxidases, whose genes are present in all white-rot Polyporales genomes and
      absent from those of brown-rot species, the H2O2-generating oxidases are widely
      distributed in both fungal types. This indicates that the GMC oxidases provide
      H2O2 for both ligninolytic peroxidase activity (in white-rot decay) and Fenton
      attack on cellulose (in brown-rot decay), after the transition between both decay
      patterns in Polyporales occurred. 

PMID- 26297779
TI  - Violaceomyces palustris gen. et sp. nov. and a new monotypic lineage,
      Violaceomycetales ord. nov. in Ustilaginomycetes.
AB  - Numerous strains of a novel yeast were isolated in Louisiana, USA, from the
      leaves of several palustrine plants, most frequently from the invasive aquatic
      ferns Salvinia minima and S. molesta. This fungus produced fast-growing colonies
      that were grayish violet to dark blue in culture and rapidly reproduced via
      production of copious ballistoconidia that germinated to form pseudohyphae.
      Colonies produced many two-celled yeasts that were distinctly hourglass-or peanut
      shaped, and occurred singly or in chains. Phylogenetic analyses of translation
      elongation factor 1-alpha, beta-tubulin and the nuc rDNA regions encompassing 28S
      D1-D2 domains, 18S and the internal transcribed spacers 1 and 2, including 5.8S,
      indicate this fungus is a member of Ustilaginomycetes but holds an isolated
      position, distinct from the two currently recognized orders, Ustilaginales and
      Urocystales. Here we describe Violaceomycetales ord. nov., Violaceomycetaceae
      fam. nov. and Violaceomyces palustris gen. et sp. nov. for this unusual fungus. 

PMID- 26297780
TI  - The nascent-polypeptide-associated complex alpha subunit regulates the
      polygalacturonases expression negatively and influences the pathogenicity of
      Sclerotinia sclerotiorum.
AB  - Sclerotinia sclerotiorum is a necrotrophic plant-pathogenic fungus that infects
      more than 400 species of plants. In this study the nascent polypeptide-associated
      complex alpha subunit gene of S. sclerotiorum (SsNACalpha; accession No.
      XP_001593856.1) was cloned and characterized. The relative transcript expression
      of SsNACalpha at different morphological stages of asexual development of S.
      sclerotiorum were analyzed by quantitative real time PCR (qRT-PCR). RNAi-mediated
      gene silencing was successful for SsNACalpha, and the mutated strains exhibited
      less than 15% of the relative expression of SsNACalpha were obtained and used for
      studying the biological functions of the gene. A delay in sclerotial maturation
      for S. sclerotiorum was observed in the SsNACalpha mutants. The significant
      elevations for both the activities of pectin-degrading enzymes and the expression
      of polygalacturonase genes also were associated with the mutated strains,
      indicating that SsNACalpha could negatively influence polygalacturonases
      expression and modulate the pathogenicity of S. sclerotiorum. 

PMID- 26297781
TI  - The Xeromphalina campanella/kauffmanii complex: species delineation and
      biogeographical patterns of speciation.
AB  - European, North American and northeastern Asian collections of Xeromphalina
      section Xeromphalina were studied by sequencing the nuc rDNA ITS1-5.8SITS2 and
      28S 5' regions and partial RNA polymerase II second largest subunit gene (RPB2).
      Previously designated Xeromphalina campanella I is designated X. campanella s.
      str. and a neotype for this species from the topotype region is established. This
      species is shown to be a discrete, cold-tolerant organism that is distributed
      across North America and Eurasia and does not exhibit significant geographical
      partitioning. A second closely related phylogenetic species previously designated
      X. campanella II, proposed as X. enigmatica, cannot be distinguished from X.
      campanella morphologically but is reproductively isolated and is sympatric with
      X. campanella across much of Eurasia and North America. Unlike X. campanella it
      shows geographical partitioning and some of the geographical populations likely
      have become reproductively isolated. Phylogenetic and geographical evidence
      suggests that X. enigmatica may have given rise to the eastern North American
      endemic, Xeromphalina kauffmanii, which also is reproductively isolated and is
      characterized by a hardwood substrate and a difference in basidiospore shape. Two
      putatively interbreeding haplotypes are evident for both eastern North American
      X. kauffmanii and eastern North American X. enigmatica and might be contributions
      from different glacial refugia. Cryptic taxa related to X. enigmatica are
      identified but not named due to small sample sizes including Asian taxa 1-5 and
      an apparent endemic from Idaho and British Columbia. Several species-delineation
      procedures were attempted and compared with this complex molecular dataset.
      Rosenberg's PAB statistic and PID (liberal) were the most liberal, assigning
      species status to haplotypes or interbreeding clades within species. PID (strict)
      and PRD (randomly distinct) were more stringent. Ability to intercross was the
      most stringent criterion for species delineation and did not correlate well with
      PAB, PID and PRD delineations. 

PMID- 26297782
TI  - Metabolite diversity in the plant pathogen Alternaria brassicicola: factors
      affecting production of brassicicolin A, depudecin, phomapyrone A and other
      metabolites.
AB  - A systematic investigation of the metabolites of Alternaria brassicicola produced
      under various culture conditions is reported. The phytotoxin brassicicolin A is
      produced in significantly larger amounts in potato dextrose broth than in minimal
      medium cultures. In general an increase in the incubation temperature of cultures
      23-30 C increases the production of brassicicolin A but decreases depudecin
      production. Reducing or eliminating nitrate from culture media or adding ammonium
      chloride increases the production of brassicicolin A at 30 C, depudecin at 23 C
      and alpha-acetylorcinol at either temperature, suggesting that nitrogen represses
      their biosynthesis. Siderophores are detected in cultures of A. brassicicola
      containing low and high ferric ion concentrations. The metabolites alpha
      acetylorcinol and tyrosol are isolated for the first time from cultures of A.
      brassicicola, and alpha-acetylorcinol is synthesized in four steps and 36%
      overall yield. Only brassicicolin A and no other isolated metabolites, including
      depudecin and phomapyrone A, display phytotoxicity on leaves of Brassica species
      (up to 5.0 mM). Epigenetic modifiers, 5-azacitidin (5-AZA), suberoylanilide
      hydroxamic acid (SAHA) and suberoyl bis-hydroxamic acid (SBHA) do not affect the
      metabolite profiles of liquid cultures of this fungal pathogen. 

PMID- 26297783
TI  - Description and phylogenetic placement of Beauveria hoplocheli sp. nov. used in
      the biological control of the sugarcane white grub, Hoplochelus marginalis, on
      Reunion Island.
AB  - On Reunion Island successful biological control of the sugarcane white grub
      Hoplochelus marginalis Fairmaire (Coleoptera: Melolonthidae) has been conducted
      for decades with strains from the entomopathogenic fungal genus Beauveria
      (Ascomycota: Hypocreales). A study based on morphological characters combined
      with a multisequence phylogenetic analysis of genes that encode the translation
      elongation factor 1-alpha (TEF1), RNA polymerase II largest subunit (RPB1), RNA
      polymerase II second largest subunit (RPB2) and the Bloc nuc intergenic region
      was carried out on Beauveria strains isolated on Reunion and Madagascar from H.
      marginalis. This study revealed that these strains, previously identified as
      Beauveria brongniartii, did not match that species and are closely related to but
      still distinct from B. malawiensis strains. Therefore we describe the Reunion
      Island fungus as the new species B. hoplocheli. 

PMID- 26297784
TI  - F-actin localization dynamics during appressorium formation in Colletotrichum
      graminicola.
AB  - Appressoria are essential penetration structures for many phytopathogenic fungi.
      Here F-actin localization dynamics were documented during appressorium formation
      in vitro and in planta in Colletotrichum graminicola Four discernible stages of
      dynamic F-actin distribution occurring in a programmed order were documented from
      differentiation of appressoria to formation of penetration pores: (stage A) from
      germ tube enlargement to complete expansion of the appressorium; (stage S)
      septation occurs; (stage L) a long period of low F-actin activity; (stage P) the
      penetration pore forms. The F-actin subcellular localization corresponded to each
      stage. A distinct redistribution of actin cables occurred at the transition from
      stage A to stage S. The in planta assays revealed that F-actin also assembled in
      invasive hyphae and that actin cables might play an essential role for
      penetration-peg development. The F-actin localization distribution may be used as
      a subcellular marker to define the developmental stages during appressorium
      formation. 

PMID- 26297785
TI  - Cupreoboletus (Boletaceae, Boletineae), a new monotypic genus segregated from
      Boletus sect. Luridi to reassign the Mediterranean species B. poikilochromus.
AB  - Cupreoboletus is erected as a new monospecific genus of Boletaceae to accommodate
      the thermophilic southern European species Boletus poikilochromus, characterized
      by discoloration toward copper-red tints overall, hymenophore forming tiny
      crystals on drying, a pervasive and long lasting sweet odor and presence of
      pseudocystidia. Macro- and microscopic descriptions of the species based on re
      examination of the type material and recent Italian collections including
      additional topotypical samples are provided and accompanied by photos and line
      drawings of the main anatomical structures. In addition, an epitype specimen is
      selected. Phylogenetic relationships were inferred from multigene molecular
      analysis based on partial sequences of the nuc rDNA 28S D1/D2 (28S) and internal
      transcribed spacer (ITS) regions and genes for ribosomal RNA polymerase II
      subunits 1 (rpb1) and 2 (rpb2) and translation-elongation factor 1-alpha
      (tef1alpha). Ecological context, geographical range and delimitation from closely
      allied taxa also were elucidated. B. martaluciae is treated as a synonym of C.
      poikilochromus according to the morphological and molecular comparative study. 

PMID- 26297786
TI  - Arrhythmia Termination Versus Elimination of Dormant Pulmonary Vein Conduction as
      a Procedural End Point of Catheter Ablation for Paroxysmal Atrial Fibrillation: A
      Prospective Randomized Trial.
AB  - BACKGROUND: Pulmonary vein isolation (PVI) is still associated with a substantial
      number of arrhythmia recurrences in paroxysmal atrial fibrillation (AF). This
      prospective, randomized study aimed to compare 2 different procedural strategies.
      METHODS AND RESULTS: A total of 152 patients undergoing de novo ablation for
      paroxysmal AF were randomized to 2 different treatment arms. The procedure in
      group A consisted of PVI exclusively. In this group, all isolated PVs were
      challenged with adenosine to reveal and ablate dormant conduction. In group B,
      PVI was performed with the patient either in spontaneous or in induced AF. If AF
      did not terminate with PVI, ablation was continued by targeting extra-PV AF
      sources with the desired procedural end point of termination to sinus rhythm.
      Primary study end point was freedom from arrhythmia during 1-year follow-up. In
      group A, adenosine provoked dormant conduction in 31 (41%) patients with a mean
      of 1.6+/-0.8 transiently recovered PVs per patient. Termination of AF during PVI
      was observed in 31 (65%) patients, whereas AF persisted afterward in 17 (35%)
      patients. AF termination occurred in 13 (76%) patients by AF source ablation.
      After 1-year follow-up, significantly more group B patients were free of
      arrhythmia recurrences (87 versus 68%; P=0.006). During redo ablation, the rate
      of PV reconduction did not differ between both groups (group A: 55% versus group
      B: 61%; P=0.25). CONCLUSIONS: Elimination of extra-PV AF sources after PVI is
      superior to sole PV isolation with the adjunct of abolishing potential dormant
      conduction. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov.
      Unique identifier: NCT02238392.

PMID- 26297787
TI  - Abnormal Left Ventricular Mechanics of Ventricular Ectopic Beats: Insights Into
      Origin and Coupling Interval in Premature Ventricular Contraction-Induced
      Cardiomyopathy.
AB  - BACKGROUND: Left ventricular (LV) dyssynchrony caused by premature ventricular
      contractions (PVCs) has been proposed as a mechanism of PVC-induced
      cardiomyopathy. We sought to understand the impact of different PVC locations and
      coupling intervals (prematurity) on LV regional mechanics and global function of
      the PVC beat itself. METHODS AND RESULTS: Using our premature pacing algorithm,
      pentageminal PVCs at coupling intervals of 200 to 375 ms were delivered from the
      epicardial right ventricular apex, RV outflow tract, and LV free wall, as well as
      premature atrial contractions, from the left atrial appendage at a coupling
      interval of 200 ms in 7 healthy canines. LV short-axis echocardiographic images,
      LV stroke volume, and dP/dtmax were obtained during all ectopic beats and
      ventricular pacing. LV dyssynchrony was assessed by dispersion of QRS-to-peak
      strain (earliest-last QRS-to-peak strain) between 6 different LV segments during
      each of the aforementioned beats (GE, EchoPac). LV dyssynchrony was greater
      during long-coupled rather than short-coupled PVCs and PVCs at 375 ms compared
      with rapid ventricular pacing at 400 ms (P<0.0001), whereas no difference was
      found between PVC locations. Longer PVC coupling intervals were associated with
      greater stroke volume and dP/dtmax despite more pronounced dyssynchrony
      (P<0.001). CONCLUSIONS: PVCs with longer coupling intervals demonstrate more
      pronounced LV dyssynchrony, whereas PVC location has minimal impact. LV
      dyssynchrony cannot be attributed to prematurity or abnormal ventricular
      activation alone, but rather to a combination of both. This study suggests that
      late-coupled PVCs may cause a more severe cardiomyopathy if dyssynchrony is the
      leading mechanism responsible for PVC-induced cardiomyopathy.

PMID- 26297788
TI  - Platelet reactivity and hemorrhage risk in neurointerventional procedures under
      dual antiplatelet therapy.
AB  - BACKGROUND AND PURPOSE: Hemorrhagic complications during neurointerventional
      procedures have various etiologies and can result in severe morbidity and
      mortality. This study investigated the possible association between low platelet
      reactivity measured by the VerifyNow assay and increased hemorrhagic
      complications during elective neurointervention under dual antiplatelet therapy.
      METHODS: From May 2010 to April 2013 we recorded baseline characteristics, P2Y12
      reaction units (PRU), and aspirin reaction units using VerifyNow. The primary
      endpoint was post-procedural hemorrhagic complications. RESULTS: A total of 279
      patients were enrolled and 31 major hemorrhagic complications (11.1%) were
      identified. From receiver-operating characteristic curve analysis, PRU values
      could discriminate between patients with and without major hemorrhagic
      complications (area under the curve 0.63). Aspirin reaction unit values had no
      association with the primary outcome. The optimal cut-off for the primary outcome
      (PRU <=175) was used to identify the low platelet reactivity group. The incidence
      of hemorrhagic complications was 20.0% in this group and 8.9% in the non-low
      platelet reactivity group. Multivariate analysis identified low platelet
      reactivity as an independent predictor for hemorrhagic complications.
      CONCLUSIONS: The risk of hemorrhagic complications during elective
      neurointervention including cerebral aneurysm coil embolization and carotid
      artery stenting under dual antiplatelet therapy is associated with the response
      to clopidogrel but not to aspirin. A PRU value of <=175 discriminates between
      patients with and without hemorrhagic complications. Future prospective studies
      are required to validate whether a specific PRU value around 170-180 is
      predictive of hemorrhagic complications.

PMID- 26297789
TI  - Interference with Virus Infection.

PMID- 26297790
TI  - Pillars Article: Virus Interference. I. The Interferon. Proc R Soc Lond B Biol
      Sci. 1957. 147: 258-267.

PMID- 26297791
TI  - Pillars Article: Virus Interference. II. Some Properties of Interferon. Proc R
      Soc Lond B Biol Sci. 1957. 147: 268-273.

PMID- 26297792
TI  - Donor Unrestricted T Cells: A Shared Human T Cell Response.
AB  - The now-famous term "restriction" derived from experiments in which T cells from
      Donor A failed to recognize Ags presented by cells from Donor B. Restriction
      results from interdonor variation in MHC genes. Donor restriction dominates
      immunologists' thinking about the T cell response because it governs organ
      transplantation and hinders the discovery of disease-associated Ags. However,
      other T cells can be considered "donor unrestricted" because their targets, CD1a,
      CD1b, CD1c, CD1d, or MR1, are expressed in a similar form among all humans. A
      striking feature of donor unrestricted T cells is the expression of invariant
      TCRs with nearly species-wide distribution. In this article, we review new
      evidence that donor unrestricted T cells are common in humans. NKT cells, mucosa
      associated invariant T cells, and germline-encoded mycolyl-reactive T cells
      operate outside of the familiar principles of the MHC system, providing a broader
      picture of T cell function and new opportunities for therapy.

PMID- 26297794
TI  - Serum amyloid A1alpha induces paracrine IL-8/CXCL8 via TLR2 and directly
      synergizes with this chemokine via CXCR2 and formyl peptide receptor 2 to recruit
      neutrophils.
AB  - Cell migration depends on the ability of leukocytes to sense an external gradient
      of chemotactic proteins produced during inflammation. These proteins include
      chemokines, complement factors, and some acute phase proteins, such as serum
      amyloid A. Serum amyloid A chemoattracts neutrophils, monocytes, and T
      lymphocytes via its G protein-coupled receptor formyl peptide receptor 2. We
      demonstrate that serum amyloid A1alpha more potently chemoattracts neutrophils in
      vivo than in vitro. In contrast to CD14(+) monocytes, no rapid (within 2 h)
      induction of interleukin-8/CXC chemokine ligand 8 or macrophage-inflammatory
      protein-1alpha/CC chemokine ligand 3 was observed in purified human neutrophils
      after stimulation of the cells with serum amyloid A1alpha or lipopolysaccharide.
      Moreover, interleukin-8/CXC chemokine ligand 8 induction in monocytes by serum
      amyloid A1alpha was mediated by toll-like receptor 2 and was inhibited by
      association of serum amyloid A1alpha with high density lipoprotein. This
      indicates that the potent chemotactic response of neutrophils toward
      intraperitoneally injected serum amyloid A1alpha is indirectly enhanced by rapid
      induction of chemokines in peritoneal cells, synergizing in a paracrine manner
      with serum amyloid A1alpha. We observed direct synergy between IL-8/CXC chemokine
      ligand 8 and serum amyloid A1alpha, but not lipopolysaccharide, in chemotaxis and
      shape change assays with neutrophils. Furthermore, the selective CXC chemokine
      receptor 2 and formyl peptide receptor 2 antagonists, SB225002 and WRW4,
      respectively, blocked the synergy between IL-8/CXC chemokine ligand 8 and serum
      amyloid A1alpha in neutrophil chemotaxis in vitro, indicating that for synergy
      their corresponding G protein-coupled receptors are required. Additionally,
      SB225002 significantly inhibited serum amyloid A1alpha-mediated peritoneal
      neutrophil influx. Taken together, endogenous (e.g., IL-1beta) and exogenous
      (e.g., lipopolysaccharide) inflammatory mediators induce primary chemoattractants
      such as serum amyloid A that synergize in an autocrine (monocyte) or a paracrine
      (neutrophil) fashion with secondary chemokines induced in stromal cells. 

PMID- 26297793
TI  - Age-Associated B Cells: A T-bet-Dependent Effector with Roles in Protective and
      Pathogenic Immunity.
AB  - A newly discovered B cell subset, age-associated B cells, expresses the
      transcription factor T-bet, has a unique surface phenotype, and accumulates
      progressively with age. Moreover, B cells with these general features are
      associated with viral infections and autoimmunity in both mice and humans. In
      this article, we review current understanding of the characteristics, origins,
      and functions of these cells. We also suggest that the protective versus
      pathogenic actions of these cells reflect appropriate versus aberrant engagement
      of regulatory mechanisms that control the Ab responses to nucleic acid-containing
      Ags.

PMID- 26297795
TI  - Soluble beta-glucan from Grifola frondosa induces tumor regression in synergy
      with TLR9 agonist via dendritic cell-mediated immunity.
AB  - The maturation of dendritic cells into more-immunostimulatory dendritic cells by
      stimulation with different combinations of immunologic agents is expected to
      provide efficient, adoptive immunotherapy against cancer. Soluble beta-glucan
      maitake D-fraction, extracted from the maitake mushroom Grifola frondosa, acts as
      a potent immunotherapeutic agent, eliciting innate and adoptive immune responses,
      thereby contributing to its antitumor activity. Here, we evaluated the efficacy
      of maitake D-fraction, in combination with a Toll-like receptor agonist, to treat
      tumors in a murine model. Our results showed that maitake D-fraction, in
      combination with the Toll-like receptor 9 agonist, cytosine-phosphate-guanine
      oligodeoxynucleotide, synergistically increased the expression of dendritic cell
      maturation markers and interleukin-12 production in dendritic cells, but it did
      not increase interleukin-10 production, generating strong effector dendritic
      cells with an augmented capacity for efficiently priming an antigen-specific, T
      helper 1-type T cell response. Maitake D-fraction enhances cytosine-phosphate
      guanine oligodeoxynucleotide-induced dendritic cell maturation and cytokine
      responses in a dectin-1-dependent pathway. We further showed that a combination
      therapy using cytosine-phosphate-guanine oligodeoxynucleotide and maitake D
      fraction was highly effective, either as adjuvants for dendritic cell vaccination
      or by direct administration against murine tumor. Therapeutic responses to direct
      administration were associated with increased CD11c(+) dendritic cells in the
      tumor site and the induction of interferon-gamma-producing CD4(+) and CD8(+) T
      cells. Our results indicate that maitake D-fraction and cytosine-phosphate
      guanine oligodeoxynucleotide synergistically activated dendritic cells, resulting
      in tumor regression via an antitumor T helper cell 1-type response. Our findings
      provide the basis for a potent antitumor therapy using a novel combination of
      immunologic agents for future clinical immunotherapy studies in patients. 

PMID- 26297796
TI  - Inherited predisposition to colorectal cancer: towards a more complete picture.
AB  - Colorectal carcinoma (CRC) is the third most common cancer worldwide. Hereditary
      factors are important in 15%-35% of affected patients. This review provides an
      update on the genetic basis of inherited predisposition to CRC. Currently known
      genetic factors include a group of highly penetrant mutant genes associated with
      rare mendelian cancer syndromes and a group of common low-penetrance alleles that
      have been identified through genetic association studies. Additional mechanisms,
      which may underlie a predisposition to CRC, will be outlined, for example,
      variants in intermediate penetrance alleles. Recent findings, including mutations
      in POLE, POLD1 and NTHL1, will be highlighted, and we identify gaps in present
      knowledge and consider how these may be addressed through current and emerging
      genomic approaches. It is expected that identification of the missing heritable
      component of CRC will be resolved through evermore comprehensive cataloguing and
      phenotypic annotation of CRC-associated variants identified through sequencing
      approaches. This will have important clinical implications, particularly in areas
      such as risk stratification, public health and CRC prevention.

PMID- 26297797
TI  - Treadmill training for patients with Parkinson's disease.
AB  - BACKGROUND: Treadmill training is used in rehabilitation and is described as
      improving gait parameters of patients with Parkinson's disease. OBJECTIVES: To
      assess the effectiveness of treadmill training in improving the gait of patients
      with Parkinson's disease and the acceptability and safety of this type of
      therapy. SEARCH METHODS: We searched the Cochrane Movement Disorders Group
      Specialised Register (see Review Group details for more information) (last
      searched September 2014), Cochrane Central Register of Controlled Trials (The
      Cochrane Library 2014, Issue 10), MEDLINE (1950 to September 2014), and EMBASE
      (1980 to September 2014). We also handsearched relevant conference proceedings,
      searched trials and research registers, and checked reference lists (last
      searched September 2014). We contacted trialists, experts and researchers in the
      field and manufacturers of commercial devices. SELECTION CRITERIA: We included
      randomised controlled trials comparing treadmill training with no treadmill
      training in patients with Parkinson's disease. DATA COLLECTION AND ANALYSIS: Two
      review authors independently selected trials for inclusion, assessed trial
      quality and extracted data. We contacted the trialists for additional
      information. We analysed the results as mean differences (MDs) for continuous
      variables and relative risk differences (RD) for dichotomous variables. MAIN
      RESULTS: We included 18 trials (6 3 3 participants) in this update of this
      review. Treadmill training improved gait speed (MD = 0.09 m/s; 95% confidence
      interval (CI) 0.03 to 0.14; P = 0.001; I(2) = 24%; m oderate quality of
      evidence), stride length (MD = 0.05 metres; 95% CI 0.01 to 0.09; P = 0.01; I(2) =
      0%; l ow quality of e vidence), but walking distance (MD = 48.9 metres; 95% CI 
      1.32 to 99.14; P = 0.06; I(2) = 91%; very low quality of evidence) and cadence
      did not improve (MD = 2.16 steps/minute; 95% CI -0.13 to 4.46; P = 0.07; I(2) =
      28%; low quality of evidence) at the end of study. Treadmill training did not
      increase the risk of patients dropping out from intervention (RD = -0.02; 95% CI 
      0.06 to 0.02; P = 0.32; I(2) = 1 3%; m oderate quality of evidence). Adverse
      events were not reported in included studies. AUTHORS' CONCLUSIONS: This update
      of our systematic review provides evidence from e ighteen trials with moderate to
      l ow risk of bias that the use of treadmill training in patients with PD may
      improve clinically relevant gait parameters such as gait speed and stride length
      (m oderate and low quality of evidence, respectively) . This apparent benefit for
      patients is, however, not supported by all secondary variables (e.g. cadence and
      walking distance ). Comparing physiotherapy and treadmill training against other
      alternatives in the treatment of gait hypokinesia such as physiotherapy without
      treadmill training this type of therapy seems to be more beneficial in practice
      without increased risk. The gain seems small to moderate clinically relevant .
      However, the results must be interpreted with caution because it is not known how
      long these improvements may last and some s tudies used no intervention in the
      control group and underlie some risk of bias . Additionally the results were
      heterogenous and we found variations between the trials in patient
      characteristics, the duration and amount of training, and types of treadmill
      training applied.

PMID- 26297798
TI  - Plants as antimalarial agents in Sub-Saharan Africa.
AB  - Although the burden of malaria is decreasing, parasite resistance to current
      antimalarial drugs and resistance to insecticides by vector mosquitoes threaten
      the prospects of malaria elimination in endemic areas. Corollary, there is a
      scientific departure to discover new antimalarial agents from nature. Because the
      two antimalarial drugs quinine and artemisinin were discovered through improved
      understanding of the indigenous knowledge of plants, bioprospecting Sub-Saharan
      Africa's enormous plant biodiversity may be a source of new and better drugs to
      treat malaria. This review analyses the medicinal plants used to manage malaria
      in Sub-Saharan Africa. Chemical compounds with antiplasmodial activity are
      described. In the Sub-Saharan African countries cited in this review, hundreds of
      plants are used as antimalarial remedies. While the number of plant species is
      not exhaustive, plants used in more than one country probably indicate better
      antimalarial efficacy and safety. The antiplasmodial data suggest an opportunity
      for inventing new antimalarial drugs from Sub-Saharan-African flora. 

PMID- 26297799
TI  - Genetic diversity of Plasmodium falciparum histidine-rich protein 2 in the China
      Myanmar border area.
AB  - Deletion of the Plasmodium falciparum histidine-rich protein 2 (pfhrp2) gene may
      affect the performance of PfHRP2-based rapid diagnostic tests (RDTs). Here we
      investigated the genetic diversity of the pfhrp2 gene in clinical parasite
      isolates collected in recent years from the China-Myanmar border area. Deletion
      of pfhrp2 has been identified in 4 out of 97 parasite isolates. Sequencing of the
      pfhrp2 exon2 from 67 isolates revealed a high level of genetic diversity in
      pfhrp2, which is reflected in the presence of many repeat types and their
      variants, as well as variable copy numbers and different arrangements of these
      repeats in parasite isolates. In addition, we observed pfhrp3 deletion in three
      of the four parasites harboring pfhrp2 deletion, suggesting of double deletions
      of both genes in these three isolates. Analysis of two cases, which were P.
      falciparum-positive by microscopy and PCR but failed by two PfHRP2-based RDTs,
      did not find pfhrp2 deletion. Further correlational studies of pfhrp2
      polymorphisms with detection sensitivity are needed to identify factors
      influencing the performance of RDTs in malaria-endemic areas. 

PMID- 26297800
TI  - The impact of time of sample collection on the measurement of thyroid stimulating
      hormone values in the serum.
AB  - OBJECTIVE: The aim of our research is to determine whether the time of blood
      sampling and fasting of patients have an impact on TSH values. DESIGN AND
      METHODS: A total of 198 participants were enrolled in this study and classified
      into five groups: A--the first sample collection for TSH measurement was taken
      between 7:00 and 8:00 a.m. at fasting and the second after 140 min without food
      intake; B--between 7:00 and 8:00 a.m. at fasting and the second after 140 min
      with food intake; C--between 7:00 and 8:00 a.m. at fasting the previous day and
      the second one between 7:00 and 8:00 a.m. at fasting the following day; D-
      between 9:00 and 10:00 a.m. at fasting the previous day and the second one
      between 9:00 and 10:00 a.m. at fasting the following day, and E--between 9:00 and
      10:00 a.m. at fasting the previous day and the second one between 7:00 and 8:00
      a.m. on the following day. Serum TSH concentration was measured by
      electrochemiluminescence immunoassay (ECLIA, Roche Diagnostics, Mannheim,
      Germany). RESULTS: TSH values (mIU/L) were in group A: 2.50 (2.20-2.81) first
      samples, 1.74 (1.52-1.96) second samples, p<0.001; B: 2.11 (1.52-2.72) first
      samples, 1.56 (1.13-1.81) second samples, p<0.001; C: 2.60 (2.28-2.91) first
      samples, 2.23 (1.92-2.53) second samples, p<0.001; D: 1.80 (1.48-2.11) first
      samples, 1.77 (1.44-2.09) second samples, p<0.597; and E: 1.32 (1.11-2.16) first
      samples, 1.67 (1.48-2.93) second samples, p<0.001. CONCLUSION: The time of sample
      collection must be standardised for the purpose of standardisation and
      harmonisation of TSH measurements.

PMID- 26297801
TI  - Three-dimensional structure of the mammalian limbal stem cell niche.
AB  - Although the existence of the limbal stem cell (LSC) niche is accepted, precise
      knowledge of its three-dimensional (3D) architecture remains incomplete. The LSC
      niche was explored on freshly excised and organ-cultured corneoscleral rims from
      human donors (n = 47), pigs (n = 15) and mice (n = 27) with full-field optical
      coherence microscopy (FFOCM). Limbal crypt features were detected in 90% of organ
      cultured human corneoscleral rims, extending between the palisades of Vogt as
      radially oriented rectangular (74% of eyes) and/or rounded (23% of eyes) forms,
      often branching off to, or becoming interconnected by, sub-scleral radially or
      circumferentially oriented crypts (in 56% of eyes). Mean crypt volume represented
      16% of sampled limbal volume on the vertical axis and 8% on the horizontal axis.
      In pigs, palisades were finer and crypts wider with relatively uniform
      distribution around the eye, and radial orientation, connecting to numerous
      narrow criss-crossing invaginations beneath the scleral surface. In mice, only a
      circumferential limbal trough was detected. Mean crypt volume represented 13% of
      sampled limbal volume in humans and 9% in pigs. FFOCM combined with fluorescence,
      and confocal fluorescence microscopy, showed presence of p63-alpha+ cells and
      cytokeratin-3+ cells in the limbal crypts. To assess colony forming efficiency
      (CFE), limbal epithelial cells were cultured at low density with mitomycin
      arrested 3T3 feeders. CFE increased with limbal crypt volume and was not
      significantly decreased in organ-cultured cornea, despite degradation of the
      epithelial roof, suggesting that stem cells remain protected at the base of
      crypts during organ culture. CFE in human samples was significantly greater than
      in pig, and CFE in mouse was zero. Crypt architecture in the three species
      appears associated with eye exposure to light. LSC density increased with
      percentage limbal volume occupied by crypts. 

PMID- 26297802
TI  - CTLA4-Ig suppresses development of experimental autoimmune uveitis in the
      induction and effector phases: Comparison with blockade of interleukin-6.
AB  - Recently, a number of biologics have been used in the treatment of autoimmune
      diseases. However, in the treatment of severe autoimmune uveitis, only TNF-alpha
      inhibitors are preferably used and the effect of other biologics such as
      interleukin-6 (IL-6) signaling blockade or cytotoxic T-lymphocyte antigen-4
      immunoglobulin fusion protein (CTLA4-Ig) has not been well studied. Previously,
      we reported that IL-6 blockade effectively suppresses the development of
      experimental autoimmune uveitis (EAU), a mouse model for uveitis, by inhibiting
      Th17 cell development. In this study, we investigated the effect of CTLA4-Ig on
      EAU development and compared it with the effect of anti-IL-6 receptor monoclonal
      antibody (MR16-1). C57BL/6J mice were immunized with interphotoreceptor retinoid
      binding protein (IRBP) and treated once with CTLA4-Ig or MR16-1. Both CTLA4-Ig
      and MR16-1 administered in the induction phase (the same day as immunization)
      significantly reduced the clinical and histopathological scores of EAU.
      Fluorescence-activated cell sorting studies using draining lymph node (LN) cells
      from EAU mice 10 days after immunization showed that CTLA4-Ig can suppress early
      T-helper cell activation. CTLA4-Ig administered in the effector phase of the
      disease (one week after immunization), when IRBP-reactive T cells have been
      primed, also significantly reduced the clinical and histopathological scores of
      EAU. In contrast, MR16-1 administered in the effector phase did not ameliorate
      EAU. To investigate the differences between these biologics in the effector
      phase, in vitro restimulation analysis of LN cells obtained from EAU mice one
      week after immunization was performed and revealed that CTLA4-Ig, but not MR16-1,
      added to culture media could inhibit the proliferation of IRBP-specific CD4(+) T
      cells which possessed capacities of producing IFN-gamma and/or IL-17.
      Collectively, CTLA4-Ig ameliorated EAU through preventing initial T-cell
      activation in the induction phase and suppressing proliferation of IRBP-specific
      T cells in the effector phase. Blockade of IL-6 signaling did not have such
      inhibitory effects after T-cell priming. CTLA4-Ig may have therapeutic effects on
      human chronic uveitis. 

PMID- 26297803
TI  - Effects of light deprivation in physical performance and psychophysiological
      responses to a time-to-exhaustion exercise test.
AB  - Studies have shown that there is no effect of light deprivation in closed-loop
      exercise performance, however less is known about the open-loop exercise
      performance. Thus, we verified if light deprivation may affect performance and
      psychophysiological responses to a time-to-exhaustion (TE), constant intensity
      exercise test. Twelve men performed TE tests (at 80% WPEAK of maximal incremental
      test) in control and light-deprived condition. Gaseous exchange (VE and VO2),
      heart rate (HR) and vastus lateralis electromyography (EMG) were continuously
      assessed, ratings of perceived exertion (RPE) and associative thoughts to
      exercise (ATE) were obtained every 60s. Responses at absolute time of exercise
      matched by the shortest time to exhaustion, and responses at exhaustion were
      compared between conditions (P<0.05). Exhaustion was shortened (5.0 +/- 1.6 min
      vs 6.4 +/- 2.4 min) and RPE slope was elevated in light deprivation, when
      compared to control (P<0.05). Responses of VE, VO2 and RPE were greater at
      exhaustion in light deprivation TE test than at the equivalent, paired time in
      control test. However, responses were similar at exhaustion of both TE tests; the
      exception was the lower EMG when the light was deprived. The light deprivation
      shortened the exhaustion and increased RPE in TE test, until the attainment of
      similar maximal psychophysiological responses.

PMID- 26297804
TI  - Conformational change of Dishevelled plays a key regulatory role in the Wnt
      signaling pathways.
AB  - The intracellular signaling molecule Dishevelled (Dvl) mediates canonical and non
      canonical Wnt signaling via its PDZ domain. Different pathways diverge at this
      point by a mechanism that remains unclear. Here we show that the peptide-binding
      pocket of the Dvl PDZ domain can be occupied by Dvl's own highly conserved C
      terminus, inducing a closed conformation. In Xenopus, Wnt-regulated convergent
      extension (CE) is readily affected by Dvl mutants unable to form the closed
      conformation than by wild-type Dvl. We also demonstrate that while Dvl cooperates
      with other Wnt pathway elements to activate canonical Wnt signaling, the open
      conformation of Dvl more effectively activates Jun N-terminal kinase (JNK). These
      results suggest that together with other players in the Wnt signaling pathway,
      the conformational change of Dvl regulates Wnt stimulated JNK activity in the non
      canonical Wnt signaling. 

PMID- 26297807
TI  - Hard coral (Porites lobata) extracts and homarine on cytochrome P450 expression
      in Hawaiian butterflyfishes with different feeding strategies.
AB  - Dietary specialists tend to be less susceptible to the effects of chemical
      defenses produced by their prey compared to generalist predators that feed upon a
      broader range of prey species. While many researchers have investigated the
      ability of insects to detoxify dietary allelochemicals, little research has been
      conducted in marine ecosystems. We investigated metabolic detoxification pathways
      in three species of butterflyfishes: the hard coral specialist feeder, Chaetodon
      multicinctus, and two generalist feeders, Chaetodon auriga and Chaetodon kleinii.
      Each species was fed tissue homogenate of the hard coral Porites lobata or the
      feeding deterrent compound homarine (found in the coral extract), and the
      expression and catalytic activity of cytochrome P450 (CYP) 3A-like and CYP2-like
      enzymes were examined after one-week of treatment. The P. lobata homogenate
      significantly induced content and catalytic activity of CYP2-like and CYP3A-like
      forms, by 2-3 fold and by 3-9 fold, respectively, in C. multicinctus. Homarine
      caused a significant decrease of CYP2-like and CYP3A-like proteins at the high
      dose in C. kleinii and 60-80% mortality in that species. Homarine also induced
      CYP3A-like content by 3-fold and catalytic activity by 2-fold in C. auriga, while
      causing non-monotonic increases in CYP2-like and CYP3A-like catalytic activity in
      C. multicinctus. Our results indicate that dietary exposure to coral homogenates
      and the feeding deterrent constituent within these homogenates caused species
      specific modulation of detoxification enzymes consistent with the prey selection
      strategies of generalist and specialist butterflyfishes. 

PMID- 26297805
TI  - Wild worm embryogenesis harbors ubiquitous polygenic modifier variation.
AB  - Embryogenesis is an essential and stereotypic process that nevertheless evolves
      among species. Its essentiality may favor the accumulation of cryptic genetic
      variation (CGV) that has no effect in the wild-type but that enhances or
      suppresses the effects of rare disruptions to gene function. Here, we adapted a
      classical modifier screen to interrogate the alleles segregating in natural
      populations of Caenorhabditis elegans: we induced gene knockdowns and used
      quantitative genetic methodology to examine how segregating variants modify the
      penetrance of embryonic lethality. Each perturbation revealed CGV, indicating
      that wild-type genomes harbor myriad genetic modifiers that may have little
      effect individually but which in aggregate can dramatically influence penetrance.
      Phenotypes were mediated by many modifiers, indicating high polygenicity, but the
      alleles tend to act very specifically, indicating low pleiotropy. Our findings
      demonstrate the extent of conditional functionality in complex trait
      architecture. 

PMID- 26297808
TI  - The oxidative stress response in freshwater-acclimated killifish (Fundulus
      heteroclitus) to acute copper and hypoxia exposure.
AB  - Aquatic organisms face multiple stressors in natural ecosystems. Here we examine
      the effects of moderate hypoxia and low-level copper (Cu) on freshwater (FW)
      acclimated killifish. Both Cu and hypoxia can affect oxidative stress in fish,
      but it is unclear if in combination these two stressors would act
      synergistically. We exposed killifish for 96h to Cu in normoxia (total 23.4+/
      0.9MUg CuL(-1)), or either no Cu (2.33+/-0.01mg O2 L(-1)) or with Cu in hypoxia
      (23.6+/-0.8MUg Cu L(-1); 2.51+/-0.04mg O2 L(-1)), and compared them to normoxic
      controls with no added Cu (0.7+/-0.1MUg Cu L(-1); 9.10+/-0.00mg O2 L(-1)) at a
      hardness of 140mgL(-1) as CaCO3 equivalents. Gills showed significant Cu
      accumulation with both excess waterborne Cu in normoxia and in hypoxia. This was
      accompanied by increases in gill catalase (CAT) activity but with no significant
      changes in either protein carbonyls or lipid peroxidation (TBARS). Hypoxia alone
      decreased gill protein carbonyls. Liver showed no change in Cu load, but a
      significant decline in CAT activity occurred with Cu in normoxia. Liver showed an
      increase in TBARS with Cu in normoxia. Cu when combined with hypoxia caused a
      significant decline in cytochrome c oxidase (COX) and citrate synthase (CS)
      activity in gill and liver. Thus, low waterborne levels of Cu and moderate
      hypoxia both affected gill and liver phenotypes. However, killifish are tolerant
      of Cu and hypoxia, and there was no evidence of a synergistic response to
      exposure to the two stressors combined compared to each stressor alone. 

PMID- 26297806
TI  - Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2
      and promote centriole duplication.
AB  - Primary microcephaly (MCPH) associated proteins CDK5RAP2, CEP152, WDR62 and CEP63
      colocalize at the centrosome. We found that they interact to promote centriole
      duplication and form a hierarchy in which each is required to localize another to
      the centrosome, with CDK5RAP2 at the apex, and CEP152, WDR62 and CEP63 at
      sequentially lower positions. MCPH proteins interact with distinct centriolar
      satellite proteins; CDK5RAP2 interacts with SPAG5 and CEP72, CEP152 with CEP131,
      WDR62 with MOONRAKER, and CEP63 with CEP90 and CCDC14. These satellite proteins
      localize their cognate MCPH interactors to centrosomes and also promote centriole
      duplication. Consistent with a role for satellites in microcephaly, homozygous
      mutations in one satellite gene, CEP90, may cause MCPH. The satellite proteins,
      with the exception of CCDC14, and MCPH proteins promote centriole duplication by
      recruiting CDK2 to the centrosome. Thus, centriolar satellites build a MCPH
      complex critical for human neurodevelopment that promotes CDK2 centrosomal
      localization and centriole duplication. 

PMID- 26297809
TI  - Alkali replacement raises urinary citrate excretion in patients with topiramate
      induced hypocitraturia.
AB  - AIMS: The aims of this study were to assess (1) the magnitude and temporality of
      decreased urinary citrate excretion in patients just starting topiramate and (2)
      the effect of alkali replacement on topiramate-induced hypocitraturia. METHODS:
      Study 1 was a prospective, non-intervention study in which patients starting
      topiramate for headache remediation provided pre- and post-topiramate 24 h urine
      collections for measurement of urine citrate. Study 2 was a clinical comparative
      effectiveness study in which patients reporting to our stone clinic for kidney
      stones and who were treated with topiramate were prescribed alkali therapy. Pre-
      and post-alkali 24 h urinary citrate excretion was compared. RESULTS: Data for 12
      and 22 patients (studies 1 and 2 respectively) were evaluated. After starting
      topiramate, urinary citrate excretion dropped significantly by 30 days (P =
      0.016) and 62% of patients had hypocitraturia (citrate <320 mg day(-1) ). At 60
      days, urine citrate was even lower than at baseline (P = 0.0032) and 86% of
      patients had developed hypocitraturia. After starting alkali, urine citrate
      increased in stone-forming patients on topiramate (198 +/- 120 to 408 +/- 274 mg
      day(-1) ; P = 0.042 for difference). 85% of patients were hypocitraturic on
      topiramate alone vs. 40% after adding alkali. The increase in urinary citrate was
      greater in patients provided >= 90 mEq potassium citrate. CONCLUSIONS: Our study
      is the first to provide clinical evidence that alkali therapy can raise urinary
      citrate excretion in patients who form kidney stones while being treated with
      topiramate. Clinicians should consider alkali therapy for reducing the kidney
      stone risk of patients benefitting from topiramate treatment for migraine
      headaches or other conditions.

PMID- 26297810
TI  - Simplified Approach to Diagnosing Sleep-Disordered Breathing and Nocturnal
      Hypercapnia in Individuals With Spinal Cord Injury.
AB  - OBJECTIVE: To evaluate a strategy of home-based testing to diagnose sleep
      disordered breathing and nocturnal hypercapnia in individuals with spinal cord
      injury (SCI). DESIGN: Case series. SETTING: Referral center. PARTICIPANTS: Adults
      with C1-T6 SCI (N=81). Individuals were eligible if >= 18 years old, with SCI of
      >= 3 months' duration, living within 100 miles of the study site, and not meeting
      exclusion criteria. Of the 161 individuals recruited from the SCI Model System
      database who were not enrolled, reasons were not interested in participating,
      change of location, prior positive pressure ventilation use, or medical
      contraindication. Ten individuals did not complete the study. INTERVENTIONS:
      Performance of an unsupervised home sleep apnea test combined with transcutaneous
      partial pressure of carbon dioxide/oxygen saturation by pulse oximetry
      monitoring. MAIN OUTCOME MEASURES: Prevalence of sleep-disordered breathing and
      nocturnal hypercapnia. Clinical and physiological variables were examined to
      determine which, if any, correlate with the severity of sleep-disordered
      breathing. RESULTS: Obstructive sleep apnea (OSA) was found in 81.3% of
      individuals, central sleep apnea (CSA) was found in 23.8%, and nonspecific
      hypopnea events, where respiratory effort was too uncertain to classify, were
      present in 35%. Nonspecific hypopnea events correlated strongly with CSA but
      weakly with OSA, suggesting that conventional sleep apnea test scoring may
      underestimate central/neuromuscular hypopneas. Nocturnal hypercapnia was present
      in 28% and oxygen desaturation in 18.3%. Neck circumference was the primary
      predictor for OSA, whereas baclofen use and obstructive apnea/hypopnea index
      weakly predicted CSA. Awake transcutaneous partial pressure of carbon dioxide and
      CSA were only marginally associated with nocturnal hypercapnia. CONCLUSIONS:
      Unsupervised home sleep apnea testing with transcutaneous capnography effectively
      identifies sleep-disordered breathing and nocturnal hypercapnia in individuals
      with SCI.

PMID- 26297812
TI  - Transcranial direct current stimulation in Parkinson's disease:
      Neurophysiological mechanisms and behavioral effects.
AB  - Recent research has highlighted the potential of transcranial direct current
      stimulation (tDCS) to complement rehabilitation effects in the elderly and in
      patients with neurological diseases, including Parkinson's disease (PD). TDCS can
      modulate cortical excitability and enhance neurophysiological mechanisms that
      compensate for impaired learning in PD. The objective of this systematic review
      is to provide an overview of the effects of tDCS on neurophysiological and
      behavioral outcome measures in PD patients, both as a stand-alone and as an
      adjunctive therapy. We systematically reviewed the literature published
      throughout the last 10 years. Ten studies were included, most of which were sham
      controlled. Results confirmed that tDCS applied to the motor cortex had
      significant results on motor function and to a lesser extent on cognitive tests.
      However, the physiological mechanism underlying the long-term effects of tDCS on
      cortical excitability in the PD brain are still unclear and need to be clarified
      in order to apply this technique optimally to a wider population in the different
      disease stages and with different medication profiles. 

PMID- 26297811
TI  - Gbx2 is essential for maintaining thalamic neuron identity and repressing
      habenular characters in the developing thalamus.
AB  - The thalamus and habenula, two important nodes of the forebrain circuitry, are
      derived from a single developmental compartment, called prosomere 2, in the
      diencephalon. Habenular and thalamic neurons display distinct molecular identity,
      neurochemistry, and connectivity. Furthermore, their progenitors exhibit
      distinctive neurogenic patterns with a marked delay in the onset of neurogenesis
      in the thalamus. However, the progenitors in prosomere 2 express many common
      developmental regulators and the mechanism underlying the specification and
      differentiation of these two populations of neurons remains unknown. Gbx2, coding
      for a homeodomain transcription factor, is initially expressed in thalamic
      neuronal precursors that have just exited the cell cycle, and its expression is
      maintained in many mature thalamic neurons in adults. Deletion of Gbx2 severely
      disrupts histogenesis of the thalamus and abolishes thalamocortical projections
      in mice. Here, by using genome-wide transcriptional profiling, we show that Gbx2
      promotes thalamic but inhibits habenular molecular characters. Remarkably,
      although Gbx2 is expressed in postmitotic neuronal precursors, deletion of Gbx2
      changes gene expression and cell proliferation in dividing progenitors in the
      developing thalamus. These defects are partially rescued by the mosaic presence
      of wild-type cells, demonstrating a cell non-autonomous role of Gbx2 in
      regulating the development of thalamic progenitors. Our results suggest that Gbx2
      is essential for the acquisition of the thalamic neuronal identity by repressing
      habenular identity through a feedback signaling from postmitotic neurons to
      progenitors.

PMID- 26297813
TI  - The magnificent seven: A quantitative review of dopamine receptor d4 and its
      association with child behavior.
AB  - A large volume of behavioral research has explored the variable number of tandem
      repeat (VNTR) polymorphism on the dopamine receptor D4 gene (DRD4). However,
      findings are inconsistent and there is no agreement about what constitutes
      "functional" and "less functional" variants at this locus. First, we
      systematically review studies exploring biological differences between DRD4 VNTRs
      (k=21). Second, we systematically review studies relating DRD4 variation to
      behavioral traits in population-based, non-clinical samples of children and
      adolescents (k=46; N=13,195), highlighting the various genotypic classifications
      previously used. Third, we use meta-analyses to examine associations of DRD4
      VNTRs with five broadly-defined behavioral outcomes (externalizing and attention
      problems, executive function, social/emotional development, and "reactive"
      temperament). We identify a significant association of "longer" DRD4 variants
      with lower levels of executive function and social/emotional development, but not
      independent of the choice of genotypic classification. We suggest that until the
      functionality of DRD4 VNTRs is established, researchers should report all
      genotypic classifications to ensure full transparency and allow for further meta
      analytic work. 

PMID- 26297814
TI  - Observation of a thermally accessible triplet state resulting from rotation
      around a main-group pi bond.
AB  - We report the first direct spectroscopic observation by electron paramagnetic
      resonance (EPR) spectroscopy of a triplet diradical that is formed in a thermally
      induced rotation around a main-group pi bond, that is, the Si?Si double bond of
      tetrakis(di-tert-butylmethylsilyl)disilene (1). The highly twisted ground-state
      geometry of singlet 1 allows access to the perpendicular triplet diradical 2 at
      moderate temperatures of 350-410 K. DFT-calculated zero-field splitting (ZFS)
      parameters of 2 accurately reproduce the experimentally observed half-field
      transition. Experiment and theory suggest a thermal equilibrium between 1 and 2
      with a very low singlet-triplet energy gap of only 7.3 kcal mol(-1) . 

PMID- 26297815
TI  - Pharmaceutical occurrence in groundwater and surface waters in forests land
      applied with municipal wastewater.
AB  - The occurrence and fate of pharmaceutical and personal care products in the
      environment are of increasing public importance because of their ubiquitous
      nature and documented effects on wildlife, ecosystems, and potentially humans.
      One potential, yet undefined, source of entry of pharmaceuticals into the
      environment is via the land application of municipal wastewater onto permitted
      lands. The objective of the present study is to determine the extent to which
      pharmaceuticals are mitigated by or exported from managed tree plantations
      irrigated with municipal wastewater. A specific focus of the present study is the
      presence of pharmaceutical compounds in groundwater and surface water discharge.
      The study site is a municipality that land-applies secondary treated wastewater
      onto 930 hectares of a 2000-hectare managed hardwood and pine plantation. A suite
      of 33 pharmaceuticals and steroid hormones was targeted in the analysis, which
      consisted of monthly grab sampling of groundwater, surface water, and wastewater,
      followed by concentration and cleanup via solid phase extraction and separation,
      detection, and quantification via liquid chromatography coupled with tandem mass
      spectrometry. More than one-half of all compounds detected in irrigated
      wastewater were not present in groundwater and subsequent surface water. However,
      antibiotics, nonsteroidal anti-inflammatory drugs, caffeine, and other
      prescription and over-the-counter drugs remained in groundwater and were
      transported into surface water at concentrations up to 10 ng/L. These results
      provide important documentation for pharmaceutical fate and transport in forest
      systems irrigated with municipal wastewater, a previously undocumented source of
      environmental entry.

PMID- 26297816
TI  - Systematic review of physical activity promotion by community health workers.
AB  - OBJECTIVE: To assess the physical activity promotion in interventions conducted
      by community health workers. METHODS: Systematic searches in five electronic
      databases (LILACS, PubMed, Scopus, Web of Science and SportDiscus) and manual
      searches in reference lists were conducted for papers published up until May
      2014. The inclusion criteria were interventions delivered in adults by community
      health workers that had physical activity promotion as an objective (primary or
      secondary). RESULTS: Of the 950 references initially retrieved, 26 were included
      in the descriptive synthesis. At the operational level, action strategies were
      predominantly based on the model of health education grounded in counseling, and
      delivered in populations at risk or diagnosed with chronic non-communicable
      diseases. Only five studies had the primary outcome of physical activity
      promotion and twenty-five studies used self-report methods for evaluation. The
      majority of studies (72.4%) were classified as having low or moderate risk of
      bias. Sixteen studies (61.5%) reported positive results for different parameters
      of physical activity. Most studies were carried out in the United States. The
      successful interventions were conducted over a period averaging 6.5 months and
      targeted mainly women, individuals older than thirty, specific ethnic groups, and
      syndromic or at-risk individuals. CONCLUSIONS: The community health workers were
      important for physical activity promotion, but further interventions should be
      carried out in different countries and less specific samples, that include
      physical activity as a primary outcome and employ direct methods for assessing
      physical activity.

PMID- 26297817
TI  - Sensitive electrochemical detection of glucose based on electrospun
      La(0.88)Sr(0.12)MnO3 naonofibers modified electrode.
AB  - Electrochemical detection of glucose in alkaline solution was performed on
      La0.88Sr0.12MnO3 (LSMO) nanofibers modified carbon paste electrode. Perovskite
      type oxide LSMO nanofibers were prepared by an electrospinning and calcination
      process. The morphologies, structures, and electrochemical behavior of the
      nanofibers were characterized by scanning electron microscope, energy dispersive
      spectrometer, X-ray diffraction, Fourier transform infrared spectrum, and cyclic
      voltammetry. The modified electrode shows excellent electrocatalytic activity
      toward glucose. Under optimal conditions, the linear response was obtained in the
      range of 0.05-100 MUM with high sensitivity and rapid response. 

PMID- 26297818
TI  - Comparison of broad-scope assays of nucleotide sugar-dependent
      glycosyltransferases.
AB  - Glycosyltransferases (GTs) are abundant in nature and diverse in their range of
      substrates. Application of GTs is, however, often complicated by their narrow
      substrate specificity. GTs with tailored specificities are highly demanded for
      targeted glycosylation reactions. Engineering of such GTs is, however, restricted
      by lack of practical and broad-scope assays currently available. Here we present
      an improvement of an inexpensive and simple assay that relies on the enzymatic
      detection of inorganic phosphate cleaved from nucleoside phosphate products
      released in GT reactions. This phosphatase-coupled assay (PCA) is compared with
      other GT assays: a pH shift assay and a commercially available immunoassay in
      Escherichia coli cell-free extract (CE). Furthermore, we probe PCA with three GTs
      with different specificities. Our results demonstrate that PCA is a versatile and
      apparently general GT assay with a detection limit as low as 1 mU. The detection
      limit of the pH shift assay is roughly 4 times higher. The immunoassay, by
      contrast, detected only nucleoside diphosphates (NDPs) but had the lowest
      detection limit. Compared with these assays, PCA showed superior robustness and,
      therefore, appears to be a suitable general screening assay for nucleotide sugar
      dependent GTs. 

PMID- 26297820
TI  - Biochemical identification of the catalytic residues of a glycoside hydrolase
      family 120 beta-xylosidase, involved in xylooligosaccharide metabolisation by gut
      bacteria.
AB  - The beta-xylosidase B from Bifidobacterium adolescentis ATCC15703 belongs to the
      newly characterized family 120 of glycoside hydrolases. In order to investigate
      its catalytic mechanism, an extensive kinetic study of the wild-type enzyme and
      mutants targeting the three highly conserved residues Asp(393), Glu(416) and
      Glu(364) was performed. NMR analysis of the xyloside hydrolysis products, the
      change of the reaction rate-limiting step for the Glu(416) mutants, the pH
      dependency of E416A activity and its chemical rescue allowed to demonstrate that
      this GH120 enzyme uses a retaining mechanism of glycoside hydrolysis, Glu(416)
      playing the role of acid/base catalyst and Asp(393) that of nucleophile. 

PMID- 26297819
TI  - Ablation of the 14-3-3gamma Protein Results in Neuronal Migration Delay and
      Morphological Defects in the Developing Cerebral Cortex.
AB  - 14-3-3 proteins are ubiquitously-expressed and multifunctional proteins. There
      are seven isoforms in mammals with a high level of homology, suggesting potential
      functional redundancy. We previously found that two of seven isoforms, 14-3
      3epsilon and 14-3-3zeta, are important for brain development, in particular,
      radial migration of pyramidal neurons in the developing cerebral cortex. In this
      work, we analyzed the function of another isoform, the protein 14-3-3gamma, with
      respect to neuronal migration in the developing cortex. We found that in utero 14
      3-3gamma-deficiency resulted in delays in neuronal migration as well as
      morphological defects. Migrating neurons deficient in 14-3-3gamma displayed a
      thicker leading process stem, and the basal ends of neurons were not able to
      reach the boundary between the cortical plate and the marginal zone. Consistent
      with the results obtained from in utero electroporation, time-lapse live imaging
      of brain slices revealed that the ablation of the 14-3-3gamma proteins in
      pyramidal neurons slowed down their migration. In addition, the 14-3-3gamma
      deficient neurons showed morphological abnormalities, including increased
      multipolar neurons with a thicker leading processes stem during migration. These
      results indicate that the 14-3-3gamma proteins play an important role in radial
      migration by regulating the morphology of migrating neurons in the cerebral
      cortex. The findings underscore the pathological phenotypes of brain development
      associated with the disruption of different 14-3-3 proteins and will advance the
      preclinical data regarding disorders caused by neuronal migration defects.

PMID- 26297821
TI  - Glycosaminoglycan silencing by engineered CXCL12 variants.
AB  - We have engineered GPCR (G protein-coupled receptor) knock-out and high GAG
      binding affinity into CXCL12alpha to inhibit CXCL12alpha-induced cell migration.
      Compared to wtCXCL12, the mutant CXCL12alpha (Delta8 L29K V39K) exhibited a 5.6
      fold and a 2.2-fold affinity increase for heparin and heparan sulfate,
      respectively. From NaCl-based heparin displacement chromatography we concluded
      that more amino acid replacements would lead to altered GAG (glycosaminoglycan)
      ligand specificity. GAG silencing by this mutant was shown in a murine seeding
      model of human cancer cells, whereby a greatly reduced number of liver metastases
      was detected when the animals were treated intravenously with 1mg/kg CXCL12alpha
      (Delta8 L29K V39K) before cancer cell application. 

PMID- 26297822
TI  - Communication between circadian clusters: The key to a plastic network.
AB  - Drosophila melanogaster is a model organism that has been instrumental in
      understanding the circadian clock at different levels. A range of studies on the
      anatomical and neurochemical properties of clock neurons in the fly led to a
      model of interacting neural circuits that control circadian behavior. Here we
      focus on recent research on the dynamics of the multiple communication pathways
      between clock neurons, and, particularly, on how the circadian timekeeping system
      responds to changes in environmental conditions. It is increasingly clear that
      the fly clock employs multiple signalling cues, such as neuropeptides, fast
      neurotransmitters, and other signalling molecules, in the dynamic interplay
      between neuronal clusters. These neuronal groups seem to interact in a plastic
      fashion, e.g., rearranging their hierarchy in response to changing environmental
      conditions. A picture is emerging supporting that these dynamic mechanisms are in
      place to provide an optimal balance between flexibility and an extraordinary
      accuracy. 

PMID- 26297823
TI  - Identification of substrates of F-box protein involved in methylmercury toxicity
      in yeast cells.
AB  - We previously reported that some of the substrate proteins recognized by Hrt3 or
      Ucc1, a component of Skp1/Cdc53/F-box protein ubiquitin ligase, may include
      proteins that are involved in the methylmercury toxicity and degraded by the
      proteasome. In this study, we found that Dld3 and Grs1 bound to Hrt3 and that
      Eno2 bound to Ucc1 using a yeast two-hybrid screening. We demonstrated that Dld3
      and Grs1 are substrates that are ubiquitinated by Hrt3, and Eno2 is a substrate
      that is ubiquitinated by Ucc1. Moreover, any yeast showing overexpression of
      Dld3, Grs1, and Eno2 demonstrated higher methylmercury sensitivity. This
      indicates that Hrt3 and Ucc1 are involved in alleviating the methylmercury
      toxicity by promoting proteasomal degradation through the ubiquitination of Dld3,
      Grs1, and Eno2. 

PMID- 26297825
TI  - A new active antimicrobial peptide from PD-L4, a type 1 ribosome inactivating
      protein of Phytolacca dioica L.: A new function of RIPs for plant defence?
AB  - We investigated the antimicrobial activity of PD-L4, a type 1 RIP from Phytolacca
      dioica. We found that this protein is active on different bacterial strains both
      in a native and denatured/alkylated form and that this biological activity is
      related to a cryptic peptide, named PDL440-65, identified by chemical
      fragmentation. This peptide showed the same antimicrobial activity of full-length
      protein and possessed, similarly to several antimicrobial peptides, an
      immunomodulatory effect on human cells. It assumes an alpha-helical conformation
      when interact with mimic membrane agents as TFE and likely bacterial membranes
      are a target of this peptide. To date PDL440-65 is the first antimicrobial
      peptide identified in a type 1 RIP. 

PMID- 26297826
TI  - Role of RSUME in inflammation and cancer.
AB  - RSUME (for RWD-domain-containing sumoylation enhancer), RWDD3 gene, was
      identified from a pituitary tumor cell with increased tumorigenic and angiogenic
      potential, and has higher expression in cerebellum, pituitary, heart, kidney,
      liver, pancreas, adrenal gland and prostate. RSUME is induced by cellular stress
      like hypoxia and heat shock, and is increased in pituitary tumors, in gliomas and
      in VHL tumors. Seven splicing forms have been described. Two of them correspond
      to non-coding RNAs and the other five possess an RWD domain in the N-terminus and
      differ in their C-terminal end. RSUME enhances SUMO conjugation by interacting
      with the SUMO conjugase Ubc9, increases Ubc9 thioester formation and therefore
      favors sumoylation of specific targets. RSUME increases IkappaB levels and
      stabilizes HIF-1alpha during hypoxia, leading to inhibition of NF-kappaB and
      increased HIF-1 transcriptional activity. RSUME inhibits pVHL function, thus
      suppressing HIF-1 and 2alpha ubiquitination and degradation. Disruption of the
      RWD domain structure of RSUME indicated that this domain is critical for RSUME
      action. The findings point to an important role of RSUME in the regulation and
      stability of specific targets, which are key regulatory mediators in cancer and
      inflammation. 

PMID- 26297824
TI  - Overcoming differences: The catalytic mechanism of metallo-beta-lactamases.
AB  - Metallo-beta-lactamases are the latest resistance mechanism of pathogenic and
      opportunistic bacteria against carbapenems, considered as last resort drugs. The
      worldwide spread of genes coding for these enzymes, together with the lack of a
      clinically useful inhibitor, have raised a sign of alarm. Inhibitor design has
      been mostly impeded by the structural diversity of these enzymes. Here we provide
      a critical review of mechanistic studies of the three known subclasses of metallo
      beta-lactamases, analyzed at the light of structural and mutagenesis
      investigations. We propose that these enzymes present a modular structure in
      their active sites that can be dissected into two halves: one providing the
      attacking nucleophile, and the second one stabilizing a negatively charged
      reaction intermediate. These are common mechanistic elements in all metallo-beta
      lactamases. Nucleophile activation does not necessarily requires a Zn(II) ion,
      but a Zn(II) center is essential for stabilization of the anionic intermediate.
      Design of a common inhibitor could be therefore approached based in these
      convergent mechanistic features despite the structural differences. 

PMID- 26297827
TI  - Binding of ouabain and marinobufagenin leads to different structural changes in
      Na,K-ATPase and depends on the enzyme conformation.
AB  - Ion pump, Na,K-ATPase specifically binds cardiotonic steroids (CTS), which leads
      to inhibition of the enzyme activity and activation of signaling network in the
      cell. We have studied interaction of Na,K-ATPase with CTS of two different types 
      marinobufagenin and ouabain. We have shown that both CTS inhibit activity of
      Na,K-ATPase with the same Ki values, but binding of ouabain is sensitive to the
      conformation of Na,K-ATPase while binding of marinobufagenin is not. Furthermore,
      binding of ouabain and marinobufagenin results in different structural changes in
      Na,K-ATPase. Our data allow to explain the diversity of effects on the receptor
      function of Na,K-ATPase caused by different types of CTS. 

PMID- 26297828
TI  - Cholesterol facilitates interactions between alpha-synuclein oligomers and charge
      neutral membranes.
AB  - Oligomeric species formed during alpha-synuclein fibrillation are suggested to be
      membrane-disrupting agents, and have been associated with cytotoxicity in
      Parkinson's disease. The majority of studies, however, have revealed that the
      effect of alpha-synuclein oligomers is only noticeable on systems composed of
      anionic lipids, while the more physiologically relevant zwitterionic lipids
      remain intact. We present experimental evidence for significant morphological
      changes in zwitterionic membranes containing cholesterol, induced by alpha
      synuclein oligomers. Depending on the lipid composition, model membranes are
      either unperturbed, disrupt, or undergo dramatic morphological changes and
      segregate into structurally different components, which we visualize by 2-photon
      fluorescence microscopy and generalized polarization analysis using the
      fluorescent probe Laurdan. Our results highlight the crucial role of cholesterol
      for mediating interactions between physiologically relevant membranes and alpha
      synuclein. 

PMID- 26297829
TI  - Contribution of autophagy to antiviral immunity.
AB  - Although identified in the 1960's, interest in autophagy has significantly
      increased in the past decade with notable research efforts oriented at
      understanding as to how this multi-protein complex operates and is regulated.
      Autophagy is commonly defined as a "self-eating" process evolved by eukaryotic
      cells to recycle senescent organelles and expired proteins, which is
      significantly increased during cellular stress responses. In addition, autophagy
      can also play important roles during human diseases, such as cancer,
      neurodegenerative and autoimmune disorders. Furthermore, novel findings suggest
      that autophagy contributes to the host defense against microbial infections. In
      this article, we review the role of macroautophagy in antiviral immune responses
      and discuss molecular mechanisms evolved by viral pathogens to evade this
      process. A role for autophagy as an effector mechanism used both, by innate and
      adaptive immunity is also discussed. 

PMID- 26297830
TI  - In various protein complexes, disordered protomers have large per-residue surface
      areas and area of protein-, DNA- and RNA-binding interfaces.
AB  - We provide first large scale analysis of the peculiarities of surface areas of
      5658 dissimilar (below 50% sequence similarity) proteins with known 3D-structures
      that bind to proteins, DNA or RNAs. We show here that area of the protein surface
      is highly correlated with the protein length. The size of the interface surface
      is only modestly correlated with the protein size, except for RNA-binding
      proteins where larger proteins are characterized by larger interfaces. Disordered
      proteins with disordered interfaces are characterized by significantly larger per
      residue areas of their surfaces and interfaces when compared to the structured
      proteins. These result are applicable for proteins involved in interaction with
      DNA, RNA, and proteins and suggest that disordered proteins and binding regions
      are less compact and more likely to assume extended shape. We demonstrate that
      disordered protein binding residues in the interfaces of disordered proteins
      drive the increase in the per residue area of these interfaces. Our results can
      be used to predict in silico whether a given protomer from the DNA, RNA or
      protein complex is likely to be disordered in its unbound form. 

PMID- 26297831
TI  - Assembly of human mitochondrial ATP synthase through two separate intermediates,
      F1-c-ring and b-e-g complex.
AB  - Mitochondrial ATP synthase is a motor enzyme in which a central shaft rotates in
      the stator casings fixed with the peripheral stator stalk. When expression of d
      subunit, a stator stalk component, was knocked-down, human cells could not form
      ATP synthase holocomplex and instead accumulated two subcomplexes, one containing
      a central rotor shaft plus catalytic subunits (F1-c-ring) and the other
      containing stator stalk components ("b-e-g" complex). F1-c-ring was also formed
      when expression of mitochondrial DNA-coded a-subunit and A6L was suppressed.
      Thus, the central rotor shaft and the stator stalk are formed separately and they
      assemble later. Similar assembly strategy has been known for ATP synthase of
      yeast and Escherichia coli and could be common to all organisms. 

PMID- 26297832
TI  - Loss of histone deacetylase Hdac1 disrupts metabolic processes in intestinal
      epithelial cells.
AB  - By using acetyl-CoA as a substrate, acetyltransferases and histone deacetylases
      regulate protein acetylation by adding or removing an acetyl group on lysines.
      Nuclear-located Hdac1 is a regulator of intestinal homeostasis. We have
      previously shown that Hdac1 define specific intestinal epithelial cell basal and
      inflammatory-dependent gene expression patterns and control cell proliferation.
      We show here that Hdac1 depletion in cellulo leads to increased histone
      acetylation after metabolic stresses, and to metabolic disturbances resulting in
      impaired responses to oxidative stresses, AMPK kinase activation and
      mitochondrial biogenesis. Thus, nuclear Hdac1 may control intestinal epithelial
      cell metabolism by regulating the supply of acetyl groups. 

PMID- 26297833
TI  - Pregnancy-associated plasma protein-A modulates the anabolic effects of
      parathyroid hormone in mouse bone.
AB  - Intermittent parathyroid hormone (PTH) is a potent anabolic therapy for bone, and
      several studies have implicated local insulin-like growth factor (IGF) signaling
      in mediating this effect. The IGF system is complex and includes ligands and
      receptors, as well as IGF binding proteins (IGFBPs) and IGFBP proteases.
      Pregnancy-associated plasma protein-A (PAPP-A) is a metalloprotease expressed by
      osteoblasts in vitro that has been shown to enhance local IGF action through
      cleavage of inhibitory IGFBP-4. This study was set up to test two specific
      hypotheses: 1) Intermittent PTH treatment increases the expression of IGF-I,
      IGFBP-4 and PAPP-A in bone in vivo, thereby increasing local IGF activity. 2) In
      the absence of PAPP-A, local IGF activity and the anabolic effects of PTH on bone
      are reduced. Wild-type (WT) and PAPP-A knock-out (KO) mice were treated with 80
      MUg/kg human PTH 1-34 or vehicle by subcutaneous injection five days per week for
      six weeks. IGF-I, IGFBP-4 and PAPP-A mRNA expression in bone were significantly
      increased in response to PTH treatment. PTH treatment of WT mice, but not PAPP-A
      KO mice, significantly increased expression of an IGF-responsive gene. Bone
      mineral density (BMD), as measured by DEXA, was significantly decreased in femurs
      of PAPP-A KO compared to WT mice with PTH treatment. Volumetric BMD, as measured
      by pQCT, was significantly decreased in femoral midshaft (primarily cortical
      bone), but not metaphysis (primarily trabecular bone), of PAPP-A KO compared to
      WT mice with PTH treatment. These data suggest that stimulation of PAPP-A
      expression by intermittent PTH treatment contributes to PTH bone anabolism in
      mice.

PMID- 26297834
TI  - Effect of SI-591, a new class of cathepsin K inhibitor with peptidomimetic
      structure, on bone metabolism in vitro and in vivo.
AB  - SI-591[N-[1-[[[(1S)-3-[[(3S)-hexahydro-2-oxo-1H-azepin-3-yl]amino]-1-(1
      methylethyl)-2,3-dioxopropyl]amino]carbonyl]cyclohexyl]-2-furancarboxamide] is an
      orally bioavailable compound that was synthesized as one of several unique
      peptidomimetic compounds without a basic group. This compound was found to have
      the ability to inhibit cathepsin K, a lysosomal cysteine protease. Cathepsin K is
      known to be expressed in osteoclasts and involved in bone loss processes. In this
      study, SI-591 was shown to inhibit the activity of various purified cathepsin
      molecules at nanomolar concentrations but had high selectivity for cathepsin K
      over other subtypes including B and L. SI-591 also decreased the level of CTX-I,
      a bone resorption marker, which was released from osteoclasts in vitro in a dose
      dependent manner. The mobilization of calcium from the bones to the blood stream
      is known to increase in rats fed with a low calcium diet; SI-591 inhibited this
      increase in serum calcium level at an oral dose of 3mg/kg. Furthermore, SI-591
      significantly decreased the level of CTX-I and DPD, bone resorption markers, at
      oral doses of 10mg/kg or less in ovariectomized rats, while it did not affect the
      level of BGP, a bone formation marker. In addition, SI-591 prevented bone mineral
      density loss in the lumber vertebrae and femurs in ovariectomized rats. These
      results suggest that SI-591 inhibits bone resorption without affecting osteoblast
      maturation. Therefore, SI-591, a novel cathepsin K inhibitor, could be a
      promising agent for the treatment of postmenopausal osteoporosis.

PMID- 26297836
TI  - The gga-let-7 family post-transcriptionally regulates TGFBR1 and LIN28B during
      the differentiation process in early chick development.
AB  - Early chick embryogenesis is governed by a complex mechanism involving
      transcriptional and post-transcriptional regulation, although how post
      transcriptional processes influence the balance between pluripotency and
      differentiation during early chick development have not been previously
      investigated. Here, we characterized the microRNA (miRNA) signature associated
      with differentiation in the chick embryo, and found that as expression of the gga
      let-7 family increases through early development, expression of their direct
      targets, TGFBR1 and LIN28B, decreases; indeed, gga-let-7a-5p and gga-let-7b
      miRNAs directly bind to TGFBR1 and LIN28B transcripts. Our data further indicate
      that TGFBR1 and LIN28B maintain pluripotency by regulating POUV, NANOG, and
      CRIPTO. Therefore, gga-let-7 miRNAs act as post-transcriptional regulators of
      differentiation in blastodermal cells by repressing the expression of the TGFBR1
      and LIN28B, which intrinsically controls blastodermal cell differentiation in
      early chick development.

PMID- 26297835
TI  - Cell Surface Human Airway Trypsin-Like Protease Is Lost During Squamous Cell
      Carcinogenesis.
AB  - Cancer progression is accompanied by increased levels of extracellular proteases
      that are capable of remodeling the extracellular matrix, as well as cleaving and
      activating growth factors and receptors that are involved in pro-cancerous
      signaling pathways. Several members of the type II transmembrane serine protease
      (TTSP) family have been shown to play critical roles in cancer progression,
      however, the expression or function of the TTSP Human Airway Trypsin-like
      protease (HAT) in carcinogenesis has not been examined. In the present study we
      aimed to determine the expression of HAT during squamous cell carcinogenesis. HAT
      transcript is present in several tissues containing stratified squamous
      epithelium and decreased expression is observed in carcinomas. We determined that
      HAT protein is consistently expressed on the cell surface in suprabasal/apical
      layers of squamous cells in healthy cervical and esophageal epithelia. To assess
      whether HAT protein is differentially expressed in normal tissue versus tissue in
      different stages of carcinogenesis, we performed a comprehensive
      immunohistochemical analysis of HAT protein expression levels and localization in
      arrays of paraffin embedded human cervical and esophageal carcinomas compared to
      the corresponding normal tissue. We found that HAT protein is expressed in the
      non-proliferating, differentiated cellular strata and is lost during the
      dedifferentiation of epithelial cells, a hallmark of squamous cell
      carcinogenesis. Thus, HAT expression may potentially be useful as a marker for
      clinical grading and assessment of patient prognosis in squamous cell carcinomas.

PMID- 26297837
TI  - Differences in promoter DNA methylation and mRNA expression of individual alleles
      of the HLA class II DQA1 gene.
AB  - OBJECTIVES: Extensive polymorphism of HLA class II genes is not restricted to the
      coding region of the gene. It extends also to the linked promoter region, where
      it forms the basis for different levels of individual allele's expression.
      Differential expression of HLA class II alleles can shape an immune response and
      influence the risk of developing autoimmune disease. In addition to genetic
      variability, variation in epigenetic modifications, including DNA methylation,
      can be another cause of the uneven expression of individual alleles. We aimed to
      analyze the DNA methylation of promoter sequences and the levels of expression of
      individual DQA1 gene alleles, interallelic variation of these two characteristics
      and the relationship between them. METHODS: The 60 healthy donors included into
      study were HLA-DRB1, HLA-DQB1 and HLA-DQA1 genotyped using PCR-SSP. Genomic DNA
      was treated by sodium bisulfite and the target segment in the HLA-DQA1 gene
      promoter was PCR amplified. PCR product was cloned into Escherichia coli and
      individual clones were sequenced. Transcripts of individual DQA1 alleles in
      peripheral blood leukocytes were quantified by Real-Time PCR. RESULTS: In this
      study, we have described detailed DNA methylation profile of promoter area of
      DQA1 gene alleles. The overall promoter methylation is increased for DQA1*02:01
      and DQA1*04:01 alleles, on the other side, DQA1*05:01 allele shows decreased
      methylation level. Our results suggest that there are only minor interindividual
      differences in DRA-normalized expression level of specific allele. Furthermore,
      expression levels of individual alleles followed DQA1*03>*01:03 (in DRB1*13
      DQA1*01:03-DQB1*06:03 haplotype)>*01:01,*05:05, and DQA1*03>*02:01>*05:05
      hierarchy. The statistically significantly most expressed allele, DQA1*03,
      comprises part of DQ8 molecule, which is commonly linked to autoimmune diseases.
      A clear relationship between promoter DNA methylation and mRNA expression level
      of the DQA1 gene could not be identified.

PMID- 26297838
TI  - Troxis necrosis, a novel mechanism for drug-induced hepatitis secondary to
      immunomodulatory therapy.
AB  - OBJECTIVES: A case of drug-induced hepatitis mediated by troxis necrosis, a form
      of autoimmune hepatitis, is described. METHODS: Clinical data, light and electron
      microscopy of an ultrasound-guided core needle liver biopsy specimen, were
      examined to investigate the cause of transaminitis in a 26year old male patient
      on Cellcept and Plaquenil for the treatment of lupus erythematosus. A systematic
      PUBMED review of troxis necrosis as the underlying mechanism for drug-induced
      hepatitis was performed. RESULTS: Liver function tests (LFTs) were significant
      for elevated AST (305) and ALT (174); the autoimmune workup was significant for
      anti-ANA positivity and alpha-SMA negativity. On light microscopy, the liver
      biopsy shows focal areas of lymphocytic infiltrates surrounding and forming
      immunologic synapses with lobular hepatocytes, indicating lobular hepatitis of
      autoimmune nature. Electron microscopy confirmed the presence of immunologic
      synapses. Upon cessation of the offending medications, the LFTs returned to
      baseline with no further intervention. Literature search yielded 7 previously
      reported cases of drug-induced hepatitis mediated by troxis necrosis. CONCLUSION:
      Troxis necrosis is a novel mechanism for drug-induced hepatitis, including
      immunomodulatory medications including a monoclonal anti-TWEAK antibody and
      Cellcept and Plaquenil, two widely used immunosuppression/anti-rejection
      medications.

PMID- 26297839
TI  - Determination and pharmacokinetic study of four xanthones in rat plasma after
      oral administration of Gentianella acuta extract by UHPLC-ESI-MS/MS.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Gentianella acuta (Michx.) Hulten belonging to
      the family of Gentianaceae is an annual plant mainly distributed in north of
      China, Mongolia plateau, Siberia and Far East areas of Russia. The whole herb was
      used as folk medicine to treat hepatitis, jaundice, headache and fever in
      Mongolia native medicine. Xanthones are the main active compounds of G. acuta and
      possess a lot of pharmacological and biological activities AIM OF THE STUDY: A
      selective and sensitive UHPLC-MS/MS method was developed and validated for the
      determination and pharmacokinetic study of swertianolin, norswertianolin,
      bellidifolin and demethylbellidifolin (DMB) in rat plasma after oral
      administration of G. acuta extract. MATERIALS AND METHODS: Sample preparation
      involved a liquid-liquid extraction of the analytes with ethyl acetate.
      Butylparaben was employed as an internal standard. LC separation was achieved on
      an Agilent SB-C18 RRHD column (1.8 MUm, 150 mm * 2.1 mm) at 30 degrees C with an
      isocratic mobile phase consisting of acetonitrile-water (0.1% formic acid)
      (90:10, v/v). The detection was accomplished by multiple-reaction monitoring
      (MRM) scanning with electrospray ionization (ESI) source operating in the
      negative ionization mode. The optimized mass transition ion-pairs (m/z) monitored
      for swertianolin, norswertianolin, bellidifolin, DMB and I.S. were 435.1/272.0,
      420.8/258.9, 273.0/258.0, 258.9/214.9 and 193.0/92.0, respectively. RESULTS: The
      current UHPLC-MS/MS assay was validated for linearity, intra-day and inter-day
      precisions, accuracy, extraction recovery and stability and was suitable for
      pharmacokinetic studies of the four xanthones after oral administration of G.
      acuta extract. The time to reach the maximum plasma concentration (Tmax) was 0.40
      +/- 0.12 h for swertianolin, 0.27 +/- 0.07 h for norswertianolin, 1.00 +/- 0.18 h
      for bellidifolin and 0.94 +/- 0.15 h for demethylbellidifolin. The elimination
      half-time (t1/2) of swertianolin, norswertianolin, bellidifolin and DMB, was 19.7
      +/- 9.64 h, 11.3 +/- 4.51 h, 19.9 +/- 8.11 h and 24.9 +/- 8.19 h, respectively.
      CONCLUSION: This study described a simple, sensitive and validated UHPLC-MS/MS
      method for simultaneous determination of four xanthones in rat plasma after oral
      administration of G. acuta extract, and investigated on their pharmacokinetic
      studies as well.

PMID- 26297840
TI  - Cyperus rotundus L.: Traditional uses, phytochemistry, and pharmacological
      activities.
AB  - ETHNO-PHARMACOLOGICAL RELEVANCE: Cyperus rotundus L. (Cyperaceae) is a medicinal
      herb traditionally used to treat various clinical conditions at home such as
      diarrhea, diabetes, pyresis, inflammation, malaria, and stomach and bowel
      disorders. Currently, it is one of the most widespread, problematic, and
      economically damaging agronomic weeds, growing wildly in various tropical and
      subtropical regions of the world. The present paper summarizes the available
      information that will aid in future medicine preparation by identifying active
      ingredients and their mode of action for a specific therapeutic activity using
      the latest technologies. MATERIAL AND METHOD: This review article is based on the
      information available on the phytochemical, toxicological, and pharmacological
      studies on and traditional uses of C. rotundus. The present paper covers the
      literature available particularly from 2000 to 2015 online (Google Scholar,
      PubMed, ScienceDirect, Scopus, SpringerLink, and Web of Science) and in books on
      phytochemistry, ethnopharmacology, and botany of this plant. RESULTS:
      Phytochemical and pharmacological studies revealed the significance of C.
      rotundus as an antiandrogenic, antibacterial, anticancerous, anticonvulsant,
      antidiabetic, antidiarrheal, antigenotoxic, anti-inflammatory, antilipidemic,
      antimalarial, antimutagenic, antiobesity, antioxidant, anti-uropathogenic,
      hepatoprotective, cardioprotective, neuroprotective, and nootropic agent. This is
      the most investigated plant worldwide due to the higher concentration of active
      ingredients in the form of essential oils, phenolic acids, ascorbic acids, and
      flavonoids in the tuber and rhizomes. Unfortunately, this significant plant
      species has not been assessed under improved cultivation conditions with the aim
      of conservation in natural habitats and high quality. CONCLUSION: Reports can be
      found on the ehtnobotanical use of C. rotundus in atherosclerosis, aging,
      apoptosis, cancer, cystitis, epilepsy, hirsutism, nociception, prostatitis, and
      genotoxicity disorders. The phytochemical and pharmacological activities of C.
      rotundus have supported its traditional as well as prospective uses as a valuable
      Ayurvedic plant. Previous researches focuses on the phytochemistry, biological
      properties and clinical application of rhizomes and tubers of C. rotundus.
      However, such studies on the other parts of this medicinally important plant are
      still quest to be investigate. Furthermore, future study should aim at confirming
      the clinical activities and safety of this plant before being used for the
      development of new therapeutic agent in human subjects.

PMID- 26297841
TI  - A new ursane triterpenoic acid and other potential anti-inflammatory and anti
      arthritic constituents from EtOAc extracts of Vitellaria paradoxa stem bark.
AB  - OBJECTIVE: Vitellaria paradoxa (shea tree) is used in traditional medicine for
      the treatment of various ailments, including, inflammation and fever. Therefore
      the present research investigates the anti-inflammatory and anti-rheumatic
      effects of V. paradoxa stem bark extracts in rats and the isolation and
      characterization of its active constituents. METHODS: The anti-inflammatory
      activity of ethyl acetate extract of V. Paradoxa (VPEE) was evaluated by use of
      the carrageenan-induced paw oedema model in rats. Moreover, rheumatoid arthritis
      (RA) was induced by injection of Freund's Completed Adjuvant (FCA) into the
      subplantar surface of the hind paw of the male Wistar rats. Paw volume was
      measured plethysmometrically. Joint swelling was measured using electronic
      vernier caliper. Hot plate test was used to assess the effect of VPEE on
      hyperalgesia while open field was used to assess the locomotors activity. The
      relative weight of spleen, liver and thymus was obtained as well as some
      haematological parameters. Tibiotarsal joint was extracted for histopathology
      under light microscope. Chemical analysis was carried out by high resolution mass
      spectrometry and one and two-dimensional NMR techniques. RESULTS: LC-MS analysis
      of the EtOAc extract revealed the presence of a new triterpenoid and several
      known compounds. The structure of the novel compound was elucidated by means of
      LC-MS and selected 1D and 2D-NMR experiments. The biological effects of ethyl
      acetate (VPEE), methanol (VPME) and water extracts (VPAE) of V. paradoxa were
      tested on carrageenan model of acute inflammation and FCA-induced rheumatoid
      arthritis animal model. In the carrageenan-induced inflammation, VPEE (150 mg/kg)
      significant (66.67%) inhibited the first (after 1h) and the second phase (4-6h)
      of edema formation. On the Complete Freund's adjuvant-induced rheumatoid
      arthritis, VPEE at the same dose showed a significantly protective effect. On
      days 19-28th of treatment, the maximum inflammatory percentage was between 9.60
      and 8.91% for the VPEE compared to 30.91-24.29% for the controls. All the
      extracts significantly reduced the score of arthritis but the maximal reduction
      was obtained with the VPEE on day 24th of the experimentation. The altered
      haematological parameters in the arthritic rats were significantly recovered to
      near normal by the treatment with VPEE at the dose of 150 mg/kg. Further
      histological studies revealed the anti-arthritic activity by preventing cartilage
      destruction of the arthritic joints of adjuvant arthritic rats. The spleen
      hypertrophy induced by the FCA was also significantly inhibited. CONCLUSION:
      These findings provide pharmacological basis for the application of the VPEE in
      inflammatory disorders.

PMID- 26297842
TI  - Inhibition of Helicobacter pylori growth and its colonization factors by
      Parthenium hysterophorus extracts.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Parthenium hysterophorus (Asteraceae) is a
      traditional medicinal plant used to treat gastrointestinal disorders, such as
      gastritis. Helicobacter pylori have been described as the etiological agent of
      gastritis, peptic ulcer, as well as gastric adenocarcinoma. 50% of the world's
      population is infected with this bacterium and the current therapy fails due to
      the increment in antibiotic resistance; therefore, it is necessary to find new
      approaches to control H. pylori infection, either by its eradication or by
      preventing the bacterial colonization. AIM OF THE STUDY: To investigate the
      effect of P. hysterophorus extracts on H. pylori growth and upon its colonization
      related factors. MATERIALS AND METHODS: Five different polarity extracts from
      roots and aerial parts of P. hysterophorus were evaluated in vitro against H.
      pylori growth by the broth dilution method. Anti-colonization activities were
      determined as follows: motility in soft agar plates, urease activity by ammonia
      colorimetrical quantification, and adherence of FITC labeled H. pylori to AGS
      cells by fluorometrical measurement. RESULTS: Organic extracts inhibited H.
      pylori growth. Particularly, the dichloromethane extract from roots showed a MIC
      of 15.6 ug/ml while the aqueous extracts showed low or null activity. There is a
      direct correlation between antibacterial activity and inhibition of motility.
      Urease activity was partially inhibited by organic extracts, at best 46%, except
      for the roots dichloromethane extract which reached 74% of inhibition with 500
      ug/ml (IC50=136.4 ug/ml). Plant extracts inhibited adherence in different ranges
      but the dichloromethane-methanol ones possessed the highest effect, with a 70%
      maximal inhibition at 1mg/ml. CONCLUSION: The results indicate that some P.
      hysterophorus extracts have various biological activities that could act
      synergistically against H. pylori. This work contributes to the ethnomedical
      knowledge of this species and underlines the potential of some organic extracts
      as a good source for the isolation of bioactive compounds.

PMID- 26297843
TI  - Antidiarrheal activity of cashew GUM, a complex heteropolysaccharide extracted
      from exudate of Anacardium occidentale L. in rodents.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Anacardium occidentale L. (Anacardiaceae) is
      commonly known as the cashew tree. It is native to tropical America and extracts
      of the leaves, bark, roots, chestnut net and exudate have been traditionally used
      in northeast Brazil for the treatment of various diseases. The exudate of the
      cashew tree (cashew gum) has been exploited by locals since ancient times for
      multiple applications, including the treatment of diarrheal diseases. AIM OF THE
      STUDY: The primary aim of the present study is to evaluate the antidiarrheal
      activity of cashew gum (CG), a complex heteropolysaccharide from the exudate of
      the cashew tree, using various models. MATERIALS AND METHODS: The antidiarrheal
      activity of cashew gum (CG) against acute diarrhea was investigated using the
      castor oil-induced diarrhea model. The effects of CG on gastrointestinal transit
      and castor oil- and PGE2- induced enteropooling were also examined in rodents. In
      addition, the effect of CG against secretory diarrhea was investigated using a
      model of fluid secretion in cholera toxin-treated intestinal closed loops in live
      mice. RESULTS: Cashew gum (30, 60, and 90 mg/kg, p.o.) showed a significant
      (P<0.05-0.01) antidiarrheal effect in rats with castor oil-induced diarrhea,
      inhibiting the total amount of stool and diarrheal stools. The 60 mg/kg dose of
      CG exhibited excellent antidiarrheal activity and significantly reduced the
      severity of diarrhea (diarrhea scores) in rats. CG (60 mg/kg) significantly
      (P<0.05) decreased the volume of castor oil- and PGE2-induced intestinal fluid
      secretion (enteropooling). In addition, similar to loperamide (standard drug, 5
      mg/kg, p.o.), CG treatment reduced the distance traveled by a charcoal meal in
      the 30-min gastrointestinal transit model by interacting with opioid receptors.
      In cholera toxin-induced secretory diarrhea, CG (60 mg/kg) significantly
      inhibited the intestinal fluid secretion and decreased Cl(-) ion loss in the
      cholera toxin(-)treated isolated loops model of live mice by competitively
      binding to cholera toxin-GM1 receptors. CONCLUSIONS: In conclusion, our results
      indicate that a complex heteropolysaccharide extracted from the exudate of A.
      occidentale L. has antidiarrheal activity in acute, inflammatory, and secretory
      diarrhea models, which could justify its traditional use in the treatment of
      diarrhea in northeast Brazil. The antidiarrheal activity might be explained by
      the capacity of CG to inhibit gastrointestinal motility and thereby reduce the
      accumulation of intestinal fluid and the secretion of water and chloride ions in
      the lumen of the intestine.

PMID- 26297844
TI  - Acute toxicity and long-term safety evaluation of the crude extract from rhizomes
      of Limonium brasiliense in mice and rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Limonium brasiliense (Boiss.) Kuntze,
      Plumbaginaceae, popularly known as baicuru, has been used in folk medicine to
      treat menstrual cramps and to regulate menstrual periods. However, little is
      known about its safety. This study evaluated the safety through in vivo tests of
      the acute, long-term, and liver toxicity, and the mutagenicity of the crude
      extract (CE) from rhizomes of L. brasiliense. MATERIALS AND METHODS: The acute
      toxicity was assessed in Swiss mice, and the chronic toxicity in Wistar rats.
      Male and female mice received the CE orally in single doses of 1.0, 2.0, 3.0,
      4.0, or 5.0 g/kg. Clinical changes and mortality rate were used as parameters to
      assess the acute toxicity. In the long-term evaluation, male and female Wistar
      rats were treated orally with daily doses of the CE (50, 100, or 200 mg/kg) for
      90 days. Assessments of weight, behavior and food intake, urinalysis, biochemical
      and hematological analyses, as well as macro- and microscopic observations of
      several organs were performed. The redox state of the liver was evaluated as a
      means of investigating the liver toxicity, and the micronucleus test to assess
      mutagenicity was also performed. RESULTS: Evaluation of acute toxicity indicated
      no apparent clinical change in the animals; the LD50 was 4.8 g/kg. Evaluation
      after 90 days administration showed that the CE, even in higher doses than are
      considered therapeutic, appeared to be safe. The micronucleus test demonstrated a
      low mutagenic potential for the CE. CONCLUSION: Our results showed that treatment
      with the CE from L. brasiliense caused low or no toxicity, as assessed using
      these doses and evaluation methods.

PMID- 26297845
TI  - A herbal formula comprising Rosae Multiflorae Fructus and Lonicerae Japonicae
      Flos inhibits the production of inflammatory mediators and the IRAK-1/TAK1 and
      TBK1/IRF3 pathways in RAW 264.7 and THP-1 cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: As documented in the Chinese Materia Medica Grand
      Dictionary (), a herbal formula (RL) consisting of Rosae Multiflorae Fructus
      (multiflora rose hips) and Lonicerae Japonicae Flos (Japanese honeysuckle
      flowers) has traditionally been used in treating inflammatory disorders. RL was
      previously reported to inhibit the expression of various inflammatory mediators
      regulated by NF-kappaB and MAPKs that are components of the TLR4 signalling
      pathways. AIM OF THE STUDY: This study aims to provide further justification for
      clinical application of RL in treating inflammatory disorders by further
      delineating the involvement of the TLR4 signalling cascades in the effects of RL
      on inflammatory mediators. MATERIALS AND METHODS: RL consisting of Rosae
      Multiflorae Fructus and Lonicerae Japonicae Flos (in 5:3 ratio) was extracted
      using absolute ethanol. We investigated the effect of RL on the production of
      cytokines and chemokines that are regulated by three key transcription factors of
      the TLR4 signalling pathways AP-1, NF-kappaB and IRF3 in LPS-stimulated RAW264.7
      cells using the multiplex biometric immunoassay. Phosphorylation of AP-1, NF
      kappaB, IRF3, IkappaB-alpha, IKKalpha/beta, Akt, TAK1, TBK1, IRAK-1 and IRAK-4
      were examined in LPS-stimulated RAW264.7 cells and THP-1 cells using Western
      blotting. Nuclear localizations of AP-1, NF-kappaB and IRF3 were also examined
      using Western blotting. RESULTS: RL reduced the secretion of various pro
      inflammatory cytokines and chemokines regulated by transcription factors AP-1, NF
      kappaB and IRF3. Phosphorylation and nuclear protein levels of these
      transcription factors were decreased by RL treatment. Moreover, RL inhibited the
      activation/phosphorylation of IkappaB-alpha, IKKalpha/beta, TAK1, TBK1 and IRAK
      1. CONCLUSIONS: Suppression of the IRAK-1/TAK1 and TBK1/IRF3 signalling pathways
      was associated with the effect of RL on inflammatory mediators in LPS-stimulated
      RAW264.7 and THP-1 cells. This provides further pharmacological basis for the
      clinical application of RL in the treatment of inflammatory disorders.

PMID- 26297846
TI  - Medicinal plants of Papua New Guinea's Miu speaking population and a focus on
      their use of plant-slaked lime mixtures.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Here we present the results of an ethnobotanical
      survey of the medicinal plants used by the Miu, a virtually unresearched
      ethnolinguistic group who live in the mountainous interior of Papua New Guinea's
      West New Britain Province. We compare the findings for those previously reported
      for the neighbouring inland Kaulong speaking population. Three species, Trema
      orientalis, Spondias dulcis and Ficus botryocarpa are used in combination with
      locally prepared slaked lime to produce intensely coloured mixtures which are
      applied to dermatological infections. Their effects on dermal fibroblast
      viability with and without slaked lime are examined. The sap of F. botryocarpa
      which is used to treat tropical ulcers was examined further with assays relevant
      to wound healing. MATERIALS AND METHODS: Focus groups and semi-structured
      interviews were used to acquire information on the uses of plants, vouchers of
      which were collected and identified by comparison with authentic herbarium
      specimens. LC-MS and NMR were used to identify chemical components. Cell
      viability assays were used to examine the effects of added slaked lime on dermal
      fibroblasts. For the sap of F. botryocarpa, fibroblast stimulation assays and
      antibacterial growth inhibition with Bacillus subtilis were carried out. RESULTS:
      The survey identified 33 plants and one fungal species, and clear differences
      with the inland Kaulong group despite their close proximity. Added slaked lime
      does not greatly increase the cytotoxicity of plant material towards dermal
      fibroblasts. The sap of F. botryocarpa contains the alkaloid ficuseptine as a
      single major component and displays antibacterial activity. CONCLUSIONS: The
      results demonstrate the potential for variation in medicinal plant use amongst
      Papua New Guinea's numerous language groups. The addition of slaked lime to plant
      material does not appear to present a concern for wound healing in the amounts
      used. The sap of F. botryocarpa displays antibacterial activity at concentrations
      that would occur at the wound surface and could be used as a highly accessible
      alternative to conventional antiseptics for remote communities in Papua New
      Guinea.

PMID- 26297847
TI  - Time-efficient determination of spin compartments by time-encoded pCASL T2
      relaxation-under-spin-tagging and its application in hemodynamic characterization
      of the cerebral border zones.
AB  - Information on water-transport across the blood-brain barrier can be determined
      from the T2 of the arterial spin labeling (ASL) signal. However, the current
      approach of using separate acquisitions of multiple inversion times is too time
      consuming for clinical (research) applications. The aim of this study was to
      improve the time-efficiency of this method by combining it with time-encoded
      pseudo-continuous ASL (te-pCASL). Furthermore, the hemodynamic properties of the
      border zone regions in the brains of healthy, young volunteers were characterized
      as an example application. The use of te-pCASL instead of multi-TI pCASL
      significantly reduced the total scan duration, while providing a higher temporal
      resolution. A significantly lower cerebral blood flow (CBF) was found in the
      border zone regions compared with the central regions in both the posterior and
      the middle cerebral artery (MCA) flow territory. The arterial transit time (ATT)
      was almost two times longer in the border zone regions than in the central
      regions (p<0.05), with an average delay in ATT of 382ms in the posterior and
      539ms in the MCA flow territory. When corrected for the ATT, the change in T2
      over time was not significantly different for the border zones as compared to the
      central regions. In conclusion, te-pCASL-TRUST provided a time-efficient method
      to distinguish spin compartments based on their T2. The ATT in the border zone is
      significantly longer than in the central region. However, the exchange of the
      label from the arterial to the tissue compartment appears to be at a similar
      rate. 

PMID- 26297848
TI  - Comparison of accelerated T1-weighted whole-brain structural-imaging protocols.
AB  - Imaging in neuroscience, clinical research and pharmaceutical trials often
      employs the 3D magnetisation-prepared rapid gradient-echo (MPRAGE) sequence to
      obtain structural T1-weighted images with high spatial resolution of the human
      brain. Typical research and clinical routine MPRAGE protocols with ~1mm isotropic
      resolution require data acquisition time in the range of 5-10min and often use
      only moderate two-fold acceleration factor for parallel imaging. Recent advances
      in MRI hardware and acquisition methodology promise improved leverage of the MR
      signal and more benign artefact properties in particular when employing increased
      acceleration factors in clinical routine and research. In this study, we examined
      four variants of a four-fold-accelerated MPRAGE protocol (2D-GRAPPA, CAIPIRINHA,
      CAIPIRINHA elliptical, and segmented MPRAGE) and compared clinical readings,
      basic image quality metrics (SNR, CNR), and automated brain tissue segmentation
      for morphological assessments of brain structures. The results were benchmarked
      against a widely-used two-fold-accelerated 3T ADNI MPRAGE protocol that served as
      reference in this study. 22 healthy subjects (age=20-44yrs.) were imaged with all
      MPRAGE variants in a single session. An experienced reader rated all images of
      clinically useful image quality. CAIPIRINHA MPRAGE scans were perceived on
      average to be of identical value for reading as the reference ADNI-2 protocol.
      SNR and CNR measurements exhibited the theoretically expected performance at the
      four-fold acceleration. The results of this study demonstrate that the four-fold
      accelerated protocols introduce systematic biases in the segmentation results of
      some brain structures compared to the reference ADNI-2 protocol. Furthermore,
      results suggest that the increased noise levels in the accelerated protocols play
      an important role in introducing these biases, at least under the present study
      conditions.

PMID- 26297849
TI  - What Gives Meaning in Life to Patients With Advanced Cancer? A Comparison Between
      Spanish, German, and Swiss Patients.
AB  - CONTEXT: Meaning in life (MiL) is a construct that varies across individuals,
      situations, cultures, and countries, and protects against emotional distress at
      the end of life. OBJECTIVES: To examine MiL in inpatients with advanced cancer
      from Barcelona, Spain, and to compare the findings with those obtained in German
      and Swiss samples. METHODS: This was a cross-sectional study in which the
      Schedule for Meaning in Life Evaluation (SMiLE) was administered. The SMiLE asks
      respondents to list individual areas that give meaning in their lives and then to
      rate their current level of importance and satisfaction with the listed areas.
      RESULTS: A total of 101 inpatients completed the SMiLE. The Index of Satisfaction
      was 76.8 +/- 21.1, the Index of Weighting was 88.0 +/- 13.0, and the Index of
      Weighted Satisfaction was 76.9 +/- 20.7. Family, partnership, well-being, and
      friends were the four areas listed by the largest proportion of Spanish patients.
      Compared with the German sample, Spanish patients were more likely to list well
      being (P < 0.01) and pleasure (P < 0.05) and less likely to list animals/nature,
      leisure time, and finances (P < 0.01). With respect to their Swiss counterparts,
      Spanish patients were more likely to list health (P < 0.01) and less likely to
      list friends, leisure time, animals/nature, and finances (P < 0.01). CONCLUSION:
      Differences were identified in the areas of MiL listed by the participants
      according to country of origin. Compared with their German and Swiss
      counterparts, the Spanish patients listed more areas involving interpersonal
      relationships. Interpersonal relationships, at both the family and wider social
      level, are reported to be the areas that give the greatest MiL to these patients.
      These aspects, therefore, should be considered when drawing up care plans
      designed to help patients achieve the maximum possible comfort and quality of
      life.

PMID- 26297850
TI  - Correlates and Predictors of Changes in Dyspnea Symptoms Over Time Among
      Community-Dwelling Palliative Home Care Clients.
AB  - CONTEXT: Dyspnea is a frequently reported and highly distressing symptom for
      persons nearing end of life, affecting the quality of living and dying.
      OBJECTIVES: This study described health and clinical characteristics of persons
      experiencing dyspnea who receive palliative home care services and identified
      factors affecting change in dyspnea over time. METHODS: Anonymized assessments (N
      = 6655 baseline; 959 follow-up) from the interRAI palliative care assessment
      instrument (interRAI PC) were collected during pilot implementation (2006-2011).
      Triggering of the interRAI PC dyspnea clinical assessment protocol was used to
      indicate presence of dyspnea. Bivariate and logistic regression analyses
      described risk and protective factors for developing new dyspnea and for recovery
      from dyspnea at follow-up. RESULTS: At baseline, 44.9% of persons exhibited
      dyspnea. Dyspnea was more prevalent among older adults, males, persons with
      shortened prognoses, and persons without cancer. Persons with dyspnea were more
      likely to experience functional impairment, moderate cognitive impairment,
      fatigue, weight loss, and urinary incontinence. Among persons with dyspnea at
      baseline, 31.5% recovered from dyspnea at follow-up. In contrast, 31% of persons
      without dyspnea at baseline reported new dyspnea at follow-up. Risk factors for
      developing new dyspnea included smoking, fatigue, and receiving oxygen therapy.
      CONCLUSION: Results highlight that dyspnea is not inevitable as persons progress
      toward death. Accordingly, dyspnea should be identified and prioritized during
      the care planning process. Integrated approaches using the interRAI PC dyspnea
      clinical assessment protocol may assist clinicians to make informed decisions
      addressing dyspnea at the person-level and thereby improve quality of life at the
      end of life.

PMID- 26297851
TI  - Differences in Physicians' Verbal and Nonverbal Communication With Black and
      White Patients at the End of Life.
AB  - CONTEXT: Black patients are more likely than white patients to die in the
      intensive care unit with life-sustaining treatments. Differences in patient-
      and/or surrogate-provider communication may contribute to this phenomenon.
      OBJECTIVES: To test whether hospital-based physicians use different verbal and/or
      nonverbal communication with black and white simulated patients and their
      surrogates. METHODS: We conducted a randomized factorial trial of the
      relationship between patient race and physician communication using high-fidelity
      simulation. Using a combination of probabilistic and convenience sampling, we
      recruited 33 hospital-based physicians in western Pennsylvania who completed two
      encounters with prognostically similar, critically and terminally ill black and
      white elders with identical treatment preferences. We then conducted detailed
      content analysis of audio and video recordings of the encounters, coding verbal
      emotion-handling and shared decision-making behaviors, and nonverbal behaviors
      (time interacting with the patient and/or surrogate, with open vs. closed
      posture, and touching the patient and physical proximity). We used a paired t
      test to compare each subjects' summed verbal and nonverbal communication scores
      with the black patient compared to the white patient. RESULTS: Subject
      physicians' verbal communication scores did not differ by patient race (black vs.
      white: 8.4 vs. 8.4, P-value = 0.958). However, their nonverbal communication
      scores were significantly lower with the black patient than with the white
      patient (black vs. white: 2.7 vs. 2.9, P-value 0.014). CONCLUSION: In this small
      regional sample, hospital-based physicians have similar verbal communication
      behaviors when discussing end-of-life care for otherwise similar black and white
      patients but exhibit significantly fewer positive, rapport-building nonverbal
      cues with black patients.

PMID- 26297852
TI  - Mediating Effect of Family Caregivers' Hesitancy to Use Analgesics on Homecare
      Cancer Patients' Analgesic Adherence.
AB  - CONTEXT: Family caregivers play an increasingly critical role in cancer patients'
      symptom management as the number of cancer patients receiving home care grows.
      However, there is a lack of research measuring the impact of the family
      caregivers' hesitancy to use analgesics on analgesic adherence and the resulting
      influence on patient pain intensity. OBJECTIVES: To examine whether family
      caregivers' hesitancy to use analgesics is a mediator that influences patient
      adherence and investigate how analgesic regimen adherence affects pain intensity.
      METHODS: This study used a cross-sectional and descriptive design. One hundred
      seventy-six patient-family caregiver dyads (N = 352) were recruited from one
      local hospital in southern Taiwan. Instruments included the Short Version of the
      Barriers Questionnaire-Taiwan, the Morisky Medication Adherence Measure-Taiwan,
      the Brief Pain Inventory-Chinese, and demographic and illness questionnaires. A
      one-way analysis of variance and post hoc comparisons were performed to assess
      the influence of analgesic regimen adherence on pain intensity. Sobel tests were
      used to examine mediating effects. RESULTS: Family caregivers' hesitancy to use
      analgesics was a significant mediator between patient barriers to use analgesics
      and patient analgesic regimen adherence (P < 0.0001). Patients with low and
      moderate adherence levels reported significantly higher levels of pain severity
      (F = 3.83, P < 0.05). CONCLUSION: This study showed that family caregivers'
      hesitancy to use analgesics was a significant mediator associated with their
      hesitancy to use analgesics and the patients' analgesic adherence. It is
      important for health care providers to consider family caregivers' hesitancy to
      use analgesics when attempting to improve adherence to pain management regimens
      in clinical practice.

PMID- 26297853
TI  - The Business Case for Palliative Care: Translating Research Into Program
      Development in the U.S.
AB  - Specialist palliative care (PC) often embraces a "less is more" philosophy that
      runs counter to the revenue-centric nature of most health care financing in the
      U.S. A special business case is needed in which the financial benefits for
      organizations such as hospitals and payers are aligned with the demonstrable
      clinical benefits for patients. Based on published studies and our work with PC
      programs over the past 15 years, we identified 10 principles that together form a
      business model for specialist PC. These principles are relatively well
      established for inpatient PC but are only now emerging for community-based PC.
      Three developments that are key for the latter are the increasing penalties from
      payers for overutilization of hospital stays, the variety of alternative payment
      models such as accountable care organizations, which foster a population health
      management perspective, and payer-provider partnerships that allow for greater
      access to and funding of community-based PC.

PMID- 26297854
TI  - ESCCAR international congress on Rickettsia and other intracellular bacteria.
AB  - The European Society for the study of Chlamydia, Coxiella, Anaplasma and
      Rickettsia (ESCCAR) held his triennial international meeting in Lausanne. This
      meeting gathered 165 scientists from 28 countries and all 5 continents, allowing
      efficient networking and major scientific exchanges. Topics covered include
      molecular and cellular microbiology, genomics, as well as epidemiology,
      veterinary and human medicine. Several breakthroughs have been revealed at the
      meeting, such as (i) the presence of CRISPR (the "prokaryotic immune system") in
      chlamydiae, (ii) an Anaplasma effector involved in host chromatin remodelling,
      (iii) the polarity of the type III secretion system of chlamydiae during the
      entry process revealed by cryo-electron tomography. Moreover, the ESCCAR meeting
      was a unique opportunity to be exposed to cutting-edge science and to listen to
      comprehensive talks on current hot topics. 

PMID- 26297856
TI  - An Alternative to MOC?

PMID- 26297855
TI  - Massachusetts Alzheimer's Disease Research Center: progress and challenges.

PMID- 26297857
TI  - Bridging the G-APP: Continuous Professional Development for Gastroenterologists:
      Replacing MOC with a Model for Lifelong Learning and Accountability.

PMID- 26297858
TI  - Absolute polarity determination of teeth cementum by phase sensitive second
      harmonic generation microscopy.
AB  - The absolute sign of local polarity in relation to the biological growth
      direction has been investigated for teeth cementum using phase sensitive second
      harmonic generation microscopy (PS-SHGM) and a crystal of 2-cyclooctylamino-5
      nitropyridine (COANP) as a nonlinear optic (NLO) reference material. A second
      harmonic generation (SHG) response was found in two directions of cementum:
      radial (acellular extrinsic fibers that are oriented more or less perpendicular
      to the root surface) and circumferential (cellular intrinsic fibers that are
      oriented more or less parallel to the surface). A mono-polar state was
      demonstrated for acellular extrinsic cementum. However, along the different parts
      of cementum in circumferential direction, two corresponding domains were observed
      featuring an opposite sign of polarity indicative for a bi-polar microscopic
      state of cellular intrinsic cementum. The phase information showed that the
      orientation of radial collagen fibrils of cementum is regularly organized with
      the donor (D) groups pointing to the surface. Circumferential collagen molecules
      feature orientational disorder and are oriented up and down in random manner
      showing acceptor or donor groups at the surface of cementum. Considering that the
      cementum continues to grow in thickness throughout life, we can conclude that the
      cementum is growing circumferentially in two opposite directions and radially in
      one direction. A Markov chain type model for polarity formation in the direction
      of growth predicts D-groups preferably appearing at the fiber front. 

PMID- 26297859
TI  - A multisensor approach to improve manometric analysis of the upper esophageal
      sphincter.
AB  - OBJECTIVES/HYPOTHESIS: High-resolution manometry (HRM) improves on previous
      manometric systems by including a greater number of sensors that are more densely
      placed. Due to deglutitive movement of the HRM catheter and upper esophageal
      sphincter (UES), it is unclear which HRM sensors capture pressure in the UES. To
      address this issue, we present two complementary studies to describe UES pressure
      patterns using HRM + videofluoroscopy and HRM + electromyography (EMG). STUDY
      DESIGN: Case series involving a new analysis method. METHODS: Study 1:
      Simultaneous HRM + videofluoroscopy were performed in 11 healthy subjects
      swallowing five 10-mL thin-liquid boluses. HRM catheter and UES movement were
      tracked to identify UES pressure patterns over multiple HRM sensors. Study 2:
      Simultaneous HRM + cricopharyngeal EMGs were performed in six healthy subjects
      swallowing five 10-mL water boluses. HRM and EMG outputs were correlated over
      individual and multiple HRM sensors. RESULTS: HRM sensors move prior to UES
      movement (P < .001) and to a lesser extent in rostral and ventral directions (P
      <= .01) than the UES. UES closure pressure is captured with two distinct
      patterns: 1) a rostral UES pattern with short durations and fast rate of pressure
      release, depicting UES descent along the catheter as it closes; and 2) a caudal
      UES pattern with tonic pressures at baseline and a deglutitive nadir. The HRM +
      EMG multisensor correlation (r = 0.88) was significantly stronger than the single
      sensor correlation (r = 0.80; P = .02). CONCLUSIONS: During deglutition, the HRM
      catheter and the UES rise above baseline positions and create a distinctive,
      multisensor manometric trace. Accurate deglutitive UES pressure evaluation must
      include multiple manometric sensors. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:657
      664, 2016.

PMID- 26297860
TI  - Expression quantitative trait loci for TNFRSF10 influence both HBV infection and
      hepatocellular carcinoma development.
AB  - Tumor necrosis factor receptor superfamily member 10 (TNFRSF10) is a death domain
      containing receptor for the apoptotic ligand TNFSF10, which involves multiple
      processes, including hepatocarcinogenesis and immune response against HBV
      infection. Several single nucleotide polymorphisms (SNPs) were identified as
      expression quantitative trait loci (eQTLs) for TNFRSF10. To assess the
      association of TNFRSF10 eQTL SNPs with the risk of hepatocellular carcinoma (HCC)
      and chronic HBV infection, we designed a case-control study that included 1,300
      HBV-related HCC patients, 1,344 chronic HBV carriers, and 1,344 subjects with HBV
      natural clearance, and then genotyped two TNFRSF10 eQTL SNPs (rs79037040 and
      rs2055822). We found that rs79037040 GT/TT genotypes were associated with a
      decreased HCC risk (adjusted odds ratio [OR] = 0.83, 95% confidence intervals
      [CIs] = 0.71-0.97, P = 0.021) but an increased chronic HBV infection risk of
      borderline significance (adjusted OR = 1.14, 95%CIs = 0.98-1.33, P = 0.085). In
      contrast, the rs2055822 G allele was a risk factor for HCC (adjusted OR = 1.12,
      95%CIs = 1.00-1.25, P = 0.041) but a protective factor for chronic HBV infection
      (adjusted OR = 0.89, 95%CIs = 0.80-0.99, P = 0.038). Furthermore, we observed a
      dose-dependent relationship between the number of alleles (rs79037040-T and
      rs2055822-A) and the risk of HCC and chronic HBV infection. In comparison with
      "0" alleles, having "1-4" alleles was significantly associated with decreased HCC
      risk and increased HBV infection risk. These findings suggest that eQTL SNPs for
      TNFRSF10 may be susceptibility markers for HCC and chronic HBV infection.

PMID- 26297861
TI  - Rat renal transplant model for mixed acute humoral and cellular rejection: Weak
      correlation of serum cytokines/chemokines with intragraft changes.
AB  - BACKGROUND: Acute renal allograft rejection remains a major cause of allograft
      dysfunction; especially for episodes with mixed humoral and cellular character
      which can be detrimental for graft survival. We established a rat RT model with
      exclusive and complete MHC-disparity to investigate pathomechanisms of acute
      rejection and evaluate serum multiplex assays as a diagnostic tool in this
      context. METHODS: LEW rats receive congeneic LEW.1W allografts (allo), no
      immunosuppression. Planned duration of the experiment was 4 weeks (n = 13 allo, n
      = 3 iso). To study kinetics of rejection, additional animals were sacrificed at
      day 7 (n = 6 allo and n = 3 iso) and day 21 (n = 3 allo). Serum cytokines and
      chemokine were longitudinally analyzed with multiplex assays in n = 5 allo and n
      = 5 controls. Allografts were assessed by histopathology, immunohisto-chemistry
      and PCR. RESULTS: Animals develop allograft dysfunction acute humoral rejection
      with additional cellular components. Donor-specific MHC-antibodies are already
      detectable at day seven (d7) after RT. Leukocytic graft infiltrates are dominated
      by macrophages and additionally consist of T-cells, B-cells and NK-cells.
      Increased intragraft expression of interleukin-2, interferon gamma, tumor
      necrosis factor alpha as well as B-cell activating factor and its receptor are
      observed. Of the 24 serum cytokines/chemokines, only CCL2 is significantly
      different (higher)in allo vs. controls at d7 (p = 0.02). CONCLUSIONS: Correlation
      of serum chemokines/cytokines with features of humoral and cellular rejection, as
      reproduced in our LEW.1W to LEW rat renal transplant model, is limited.
      Macrophages, B-cells and their signaling pathways deserve more attention in
      genesis and possibly also treatment of acute rejection.

PMID- 26297862
TI  - Hydrogen sulfide in cancer: Friend or foe?
AB  - Hydrogen sulfide (H2S) is the third gaseous signaling molecule that plays
      important roles in cancer biological processes. Recent studies indicate that H2S
      has both pro-cancer and anti-cancer effects. Endogenous H2S can exert pro-cancer
      functions through induction of angiogenesis regulation of mitochondrial
      bioenergetics, acceleration of cell cycle progression, and anti-apoptosis
      mechanisms. Thus, the inhibition of the production of H2S in cancer cells may be
      a new cancer treatment strategy. In contrast to the pro-cancer effect of H2S,
      relatively high concentrations of exogenous H2S could suppress the growth of
      cancer cells by inducing uncontrolled intracellular acidification, inducing cell
      cycle arrest, and promoting apoptosis. Therefore, H2S donors and H2S-releasing
      hybrids could be designed and developed as novel anti-cancer drugs. In this
      review, the production and metabolism of H2S in cancer cells are summarized and
      the role and mechanism of H2S in cancer development and progression are further
      discussed.

PMID- 26297863
TI  - Advances in the treatment of cognitive impairment in Parkinson's disease.
AB  - Cognitive impairment in Parkinson's disease (PD) is a frequent complication, with
      significant interindividual variability in clinical symptoms, severity, timing,
      and neural substrates. Recent studies have focused not only on understanding PD
      dementia, but also mild cognitive impairment in PD, which may represent a
      prodromal stage for dementia. In recent years, there have been important advances
      regarding clinical characterizations, definitions, associated biomarkers, and
      risk factors for both mild cognitive impairment in PD and PD dementia. However,
      there is a paucity of effective therapies for cognitive impairment in PD, whether
      for mild symptoms or for moderate to severe dementia. At present, only
      rivastigmine is U.S. Food and Drug Administration approved for PD dementia, an
      indication received nearly a decade ago. Given the frequency of PD cognitive
      impairment and its substantial impact on both patients and families, the lack of
      available and effective treatments represents a striking gap in the field,
      especially when compared to the large number of available therapies for PD motor
      symptoms and complications. Improved symptomatic therapies, as well as potential
      disease-modifying agents, for PD cognitive impairment are needed. Most
      therapeutic trials for PD dementia and mild cognitive impairment in PD have
      focused on drugs developed for and tested in Alzheimer's disease, such as
      cholinesterase inhibitors and the N-methyl-D-aspartate receptor antagonist,
      memantine, though recent and ongoing trials examine the effects of
      pharmacological agents affecting other neurotransmitters, as well as
      nonpharmacological therapies, including mental and physical exercise and
      neurostimulation. This review summarizes the design and outcomes of trials for PD
      cognitive impairment published since 2013 and highlights future therapeutic
      research opportunities and challenges.

PMID- 26297864
TI  - Central corticosterone disrupts behavioral and neuroendocrine responses during
      lactation.
AB  - Administration of a high dose of chronic peripheral corticosterone during the
      postpartum period has been shown to lead to reduced maternal care, but the
      interference of acute corticosterone, mimicking a situation of acute stress, on
      maternal behavior has not been well established. Therefore, the aim of our study
      was to investigate the influence of acute central corticosterone on behavioral
      and neuroendocrine responses during lactation. On day 7 of lactation, female rats
      were treated with vehicle (5 MUL; i.c.v.) or corticosterone (10 ng/5 MUL; i.c.v.)
      30 min before the start of the experiment. To evaluate maternal behavior, the
      pups were returned to the side of their home cages opposite the previous nest,
      and the resulting behavior of the lactating rats was filmed for the next 30 min.
      Plasma levels of oxytocin and the amount of milk consumed by the pups were
      evaluated 15 min after the onset of suckling. In addition, the double-labeled c
      Fos/oxytocin neurons in the paraventricular nucleus (PVN) and supraoptic nucleus
      (SON) and c-Fos immunoreactivity in medial preoptic area (MPOA) neurons were
      quantified for each lactating rat. Corticosterone decreased maternal care, plasma
      oxytocin levels, milk consumption by the pups, the activation of oxytocinergic
      neurons in hypothalamic nuclei, and c-Fos immunoreactivity in MPOA neurons. Our
      results indicate that changes in the behavioral responses of lactating rats
      treated with corticosterone may be related to disruption of the neuroendocrine
      control of oxytocin secretion.

PMID- 26297865
TI  - Regulation of leukocyte tricarboxylic acid cycle in drug-naive Bipolar Disorder.
AB  - Several lines of evidence suggest a role for mitochondrial dysfunction in the
      pathophysiology of bipolar disorder (BD). The tricarboxylic acid cycle (TCA
      cycle) is fundamental for mitochondrial energy production and produces substrates
      used in oxidative phosphorylation by the mitochondrial electron transport chain.
      The activity of the key TCA cycle enzymes citrate synthase, malate dehydrogenase,
      and succinate dehydrogenase has never been evaluated in BD. In the present study,
      these enzymes were assayed from leukocytes of drug-naive BD patients in a major
      depressive episode (n=18) and compared to 24 age-matched healthy controls. Drug
      naive BD patients did not show differences in activities of citrate synthase
      (p=0.79), malate dehydrogenase (p=0.17), and succinate dehydrogenase (p=0.35)
      compared with healthy controls. No correlation between any TCA cycle enzyme
      activity and severity of depressive symptoms was observed. Overall, these data
      suggest that the activities of the TCA cycle enzymes are not altered in major
      depressive episodes of recent-onset BD, which may support the concept of illness
      staging and neuroprogression in BD. 

PMID- 26297866
TI  - SIRT1 contributes to aldose reductase expression through modulating NFAT5 under
      osmotic stress: In vitro and in silico insights.
AB  - So far, a myriad of molecules were characterized to modulate NFAT5 and its
      downstream targets. Among these NFAT5 modifiers, SIRT1 was proposed to have a
      promising role in NFAT5 dependent events, yet the exact underlying mechanism
      still remains obscure. Hence, the link between SIRT1 and NFAT5-aldose reductase
      (AR) axis under osmotic stress, was aimed to be delineated in this study. A
      unique osmotic stress model was generated and its mechanistic components were
      deciphered in U937 monocytes. In this model, AR expression and nuclear NFAT5
      stabilization were revealed to be positively regulated by SIRT1 through
      utilization of pharmacological modulators. Overexpression and co-transfection
      studies of NFAT5 and SIRT1 further validated the contribution of SIRT1 to AR and
      NFAT5. The involvement of SIRT1 activity in these events was mediated via
      modification of DNA binding of NFAT5 to AR ORE region. Besides, NFAT5 and SIRT1
      were also shown to co-immunoprecipitate under isosmotic conditions and this
      interaction was disrupted by osmotic stress. Further in silico experiments were
      conducted to investigate if SIRT1 directly targets NFAT5. In this regard, certain
      lysine residues of NFAT5, when kept deacetylated, were found to contribute to its
      DNA binding and SIRT1 was shown to directly bind K282 of NFAT5. Based on these in
      vitro and in silico findings, SIRT1 was identified, for the first time, as a
      novel positive regulator of NFAT5 dependent AR expression under osmotic stress in
      U937 monocytes. 

PMID- 26297868
TI  - Efficacy and safety of therapeutic ERCP in patients with cirrhosis: a large
      multicenter study.
AB  - BACKGROUND AND AIMS: Patients with cirrhosis may be less than optimal candidates
      for ERCP because of underlying ascites, coagulopathy, encephalopathy, and other
      problems. Although the risks of surgery in patients with cirrhosis are well
      known, few data are available regarding ERCP in patients with cirrhosis. We
      performed a retrospective, multicenter study of ERCP in patients with cirrhosis
      to evaluate outcomes, efficacy, and safety. METHODS: Multicenter retrospective
      study. RESULTS: A total of 538 ERCP procedures were performed on 328 patients
      with cirrhosis. A total of 229 patients had Child-Pugh (CP) class A, 229 patients
      had CP class B, and 80 patients had CP class C. Thrombocytopenia and coagulopathy
      were corrected before ERCP. The 30-day, procedure-related adverse events included
      post-ERCP pancreatitis (n = 25, 4.6%: 21 mild, 3 moderate, 1 severe), hemorrhage
      (n = 6, 1.1%), cholangitis (n = 15, 2.8%), perforation (n = 2, 0.4%), aspiration
      pneumonia (n = 5, 0.9%), bile leakage (n = 1, 0.2%), cholecystitis (n = 1, 0.2%),
      and death (n = 1, 0.2%). There was a higher incidence of adverse events in
      patients with CP class B and C disease when compared with those with CP class A
      disease (11.4%, 11.3%, and 6.1%, respectively; P = .048). There was no
      correlation between the risk of significant hemorrhage and the presence of
      coagulopathy or CP class, even in those who underwent a sphincterotomy. The
      presence of poorly controlled encephalopathy correlated with a higher overall
      adverse event rate (P = .003). Sub-analysis revealed that patients without
      primary sclerosing cholangitis had a significantly higher overall rate of adverse
      events, pancreatitis, bleeding, and cardiopulmonary adverse events after ERCP
      when compared with those with primary sclerosing cholangitis. CONCLUSIONS: Our
      study was performed on a large series of patients with cirrhosis undergoing ERCP.
      Overall, the adverse events seen in patients with cirrhosis are similar to those
      seen in the general population of patients undergoing ERCP, although patients
      with CP classes B and C have higher adverse event rates compared with those with
      CP class A. Patients with cirrhosis without primary sclerosing cholangitis had
      significantly greater adverse event rates when compared with patients with
      primary sclerosing cholangitis.

PMID- 26297869
TI  - A rare case of non-Epstein-Barr virus-associated lymphoepithelioma-like carcinoma
      of the esophagus treated with endoscopic submucosal dissection.

PMID- 26297870
TI  - Preoperative indicators of failure of en bloc resection or perforation in
      colorectal endoscopic submucosal dissection: implications for lesion
      stratification by technical difficulties during stepwise training.
AB  - BACKGROUND AND AIMS: The technical difficulties inherent in endoscopic submucosal
      dissection (ESD) for colorectal neoplasms may result in the failure of en bloc
      resection or perforation. The aim of this retrospective study was to assess the
      predictors of en bloc resection failure or perforation by using preoperatively
      available factors. METHODS: Between September 2002 and March 2013, 716 colorectal
      ESDs in 673 consecutive patients were performed at a tertiary cancer center.
      Patient characteristics, tumor location, tumor type, colonoscopy-related factors,
      and endoscopist experience were assessed based on a prospectively recorded
      institutional ESD database. Logistic regression analysis was performed to
      identify predictors of failure of en bloc resection or perforations, with
      subgroup analyses of ESDs performed by endoscopists less experienced in
      colorectal ESD (<40 cases) and for colonic lesions only. RESULTS: On multivariate
      analysis, independent predictors of failure of en bloc resection or perforations
      were the presence of fold convergence (odds ratio [OR] 4.4; 95% confidence
      interval [95% CI], 1.9-9.9), protruding type (OR 3.6; 95% CI, 1.8-7.1), poor
      endoscope operability (OR 3.5; 95% CI, 1.8-6.9), right-sided colonic lesions (OR
      3.0; 95% CI, 1.5-6.3 vs rectal lesions), left-sided colonic lesions (OR 3.2; 95%
      CI, 1.7-6.3, vs rectal lesions), the presence of an underlying semilunar fold (OR
      2.1; 95% CI, 1.3-3.6), and a less-experienced endoscopist (OR 2.1; 95% CI, 1.3
      3.6). Among less-experienced endoscopists, colonic lesions were independent
      predictors (right-sided colonic lesions 8.1; 95% CI, 2.9-25.1; left-sided colonic
      lesions 8.1; 95% CI, 2.5-28.3 vs rectal lesions). For colonic lesions, the
      presence of fold convergence (OR 3.7; 95% CI, 1.6-8.6), poor endoscope
      operability (OR 3.6; 95% CI, 1.8-7.2), a less-experienced endoscopist (OR 3.0;
      95% CI, 1.7-1.8), and the presence of an underlying semilunar fold (OR 2.7; 95%
      CI, 1.5-4.7) were identified predictors. CONCLUSION: This study successfully
      identified predictors of en bloc resection failure or perforation. Understanding
      these indicators could help to accurately stratify lesions according to technical
      difficulty and to appropriately select endoscopists.

PMID- 26297871
TI  - "Here's looking at you, kid".

PMID- 26297867
TI  - Otolaryngology-head and neck surgery at Johns Hopkins: The first 100 years (1914
      2014).

PMID- 26297873
TI  - Proliferative laryngitis with airway obstruction in an adult: Consider herpes.
AB  - OBJECTIVES/HYPOTHESIS: Few cases of herpes simplex virus (HSV) affecting the
      larynx have been reported in the literature. Although HSV laryngitis appears to
      present with nonspecific symptoms, this is a potentially serious condition that
      can rapidly progress to unnecessary morbidity and mortality if not identified and
      treated accordingly. We report a case of HSV laryngitis in an individual with
      well controlled human immunodeficiency virus infection and perform a
      comprehensive literature review of HSV laryngitis in adults. From this case
      report and review of the literature, we advocate early diagnostic biopsy of
      unusual or poorly responsive laryngeal lesions for pathology, culture, and
      virology studies.

PMID- 26297872
TI  - Wnt/beta-catenin and sonic hedgehog pathways interact in the regulation of the
      development of the dorsal mesenchymal protrusion.
AB  - BACKGROUND: The dorsal mesenchymal protrusion (DMP) is a second heart field (SHF)
      derived tissue involved in cardiac septation. Molecular mechanisms controlling
      SHF/DMP development include the Bone Morphogenetic Protein and Wnt/beta-catenin
      signaling pathways. Reduced expression of components in these pathways leads to
      inhibition of proliferation of the SHF/DMP precursor population and failure of
      the DMP to develop. While the Sonic Hedgehog (Shh) pathway has also been
      demonstrated to be critically important for SHF/DMP development and
      atrioventricular septation, its role in the regulation of SHF proliferation is
      contentious. RESULTS: Tissue-specific deletion of the Shh receptor Smoothened
      from the SHF resulted in compromised DMP formation and atrioventricular septal
      defects (AVSDs). Immunohistochemical analysis at critical stages of DMP
      development showed significant proliferation defect as well as reduction in
      levels of the Wnt/beta-catenin pathway-intermediates beta-catenin, Lef1, and
      Axin2. To determine whether the defects seen in the conditional Smoothened knock
      out mouse could be attributed to reduced Wnt/beta-catenin signaling, LiCl, a
      pharmacological activator of this Wnt/beta-catenin pathway, was administered.
      This resulted in restoration of proliferation and partial rescue of the AVSD
      phenotype. CONCLUSIONS: The data presented suggest that the Wnt/beta-catenin
      pathway interact with the Shh pathway in the regulation of SHF/DMP-precursor
      proliferation and, hence, the development of the DMP.

PMID- 26297874
TI  - Reduced risk of pertussis in whole-cell compared to acellular vaccine recipients
      is not confounded by age or receipt of booster-doses.
AB  - Several observational studies provide evidence that acellular pertussis vaccines
      (aP) are less protective against pertussis disease than highly effective whole
      cell pertussis vaccines (wP), however, concerns have been raised that some of
      these findings may be confounded by age. By undertaking age-stratified and
      restricted analyses on a cohort of Australian children primed with either aP
      only, wP-only or mixed pertussis vaccine schedules, we demonstrate that compared
      to aP the association of wP with increased protection from pertussis is not
      confounded by age, nor by aP booster-dose receipt.

PMID- 26297875
TI  - Impact of pneumococcal conjugate vaccines on childhood otitis media in the United
      Kingdom.
AB  - BACKGROUND: Studies have demonstrated a reduction for otitis media (OM) following
      the introduction of seven-valent pneumococcal conjugate vaccine (PCV7), but this
      has not been evaluated in the United Kingdom (UK). Moreover, there are limited
      data on any additional impact of PCV13 introduction in 2010. METHODS: We
      conducted an observational cohort study to investigate the trends in OM incidence
      and associated antibiotic prescriptions in children aged <10 year-olds during
      2002-2012 using a national primary care database. Three time-periods were defined
      to estimate monthly incidence: pre-PCV7 (January 2002-August 2006), post-PCV7
      (September 2007-March 2010), and post-PCV13 (April 2011-December 2012). RESULTS:
      Overall annual OM incidence declined by 51.3% from 135.8 episodes/1000 person
      years in 2002 to 66.1 episodes/1000 person-years in 2012; antibiotic prescription
      rates for OM declined by 72.9% from 57.9 prescriptions/1000 person-years to 15.7
      prescriptions/1000 person-years, respectively. PCV7 introduction was associated
      with significant decline in OM rates across all age-groups (21.8%; 95% CI, 20.2
      23.4), including <2 year-olds (19.8%; 95% CI, 16.0-23.5%); 2-4 year-olds (23.0%;
      95% CI, 20.4-25.4%) and 5-9 year-olds (20.2%; 95% CI, 17.6-22.7%). There was an
      additional significant reduction in OM (18.5%; 95% CI, 16.7-20.2%) and associated
      antibiotic prescribing (12.2%; 95% CI, 8.6-15.6%) after the introduction of PCV13
      across all age-groups. CONCLUSION: The introduction of PCV7 was associated with a
      22% significant reductions in OM in children aged <10 year-olds with an
      additional 19% reductions after PCV13 introduction. These declines are equivalent
      to 592,000 and 15,700 fewer consultations and OM-related hospitalizations,
      respectively, in England and Wales every year. Although the continuing decline in
      OM rates in our study suggests that further reduction may continue to occur, it
      is important to monitor long-term trends in all pneumococcal diseases, including
      OM and pneumonia, because of increasing replacement of non-vaccine pneumococcal
      serotypes in carriage and disease.

PMID- 26297876
TI  - Jun N-terminal kinase activity is required for invagination but not
      differentiation of the sea urchin archenteron.
AB  - Although sea urchin gastrulation is well described at the cellular level, our
      understanding of the molecular changes that trigger the coordinated cell
      movements involved is not complete. Jun N-terminal kinase (JNK) is a component of
      the planar cell polarity pathway and is required for cell movements during
      embryonic development in several animal species. To study the role of JNK in sea
      urchin gastrulation, embryos were treated with JNK inhibitor SP600125 just prior
      to gastrulation. The inhibitor had a limited and specific effect, blocking
      invagination of the archenteron. Embryos treated with 2 MUM SP600125 formed
      normal vegetal plates, but did not undergo invagination to form an archenteron.
      Other types of cell movements, specifically ingression of the skeletogenic
      mesenchyme, were not affected, although the development and pattern of the
      skeleton was abnormal in treated embryos. Pigment cells, derived from
      nonskeletogenic mesenchyme, were also present in SP600125-treated embryos.
      Despite the lack of a visible archenteron in treated embryos, cells at the
      original vegetal plate expressed several molecular markers for endoderm
      differentiation. These results demonstrate that JNK activity is required for
      invagination of the archenteron but not its differentiation, indicating that in
      this case, morphogenesis and differentiation are under separate regulation.

PMID- 26297877
TI  - The pescatorial sixth.
AB  - A 56-year-old man with diabetes presented with acute diplopia and signs of
      bilateral complete abduction deficits. Diffuse areflexia was his only other sign
      at presentation. Within a few days, he developed complete ophthalmoplegia and
      ataxia, consistent with a clinical diagnosis of Miller-Fisher syndrome, and
      repeated history revealed a possible gastroenteritis 3 weeks prior. This case
      illustrates an "ophthalmoplegia without ataxia" variant of this classic
      autoimmune condition, which should be considered in patients presenting with
      bilateral VI nerve palsies.

PMID- 26297878
TI  - Biomimetic repeat protein derived from Xenopus tropicalis for fibrous scaffold
      fabrication.
AB  - Collagen, silk, and elastin are the fibrous proteins consist of representative
      amino acid repeats. Because these proteins exhibited distinguishing mechanical
      properties, they have been utilized in diverse applications, such as fiber-based
      sensors, filtration membranes, supporting materials, and tissue engineering
      scaffolds. Despite their infinite prevalence and potential, most studies have
      only focused on a few repeat proteins. In this work, the hypothetical protein
      with a repeat motif derived from the frog Xenopus tropicalis was obtained and
      characterized for its potential as a novel protein-based material. The codon
      optimized recombinant frog repeat protein, referred to as 'xetro', was produced
      at a high rate in a bacterial system, and an acid extraction-based purified xetro
      protein was successfully fabricated into microfibers and nanofibers using wet
      spinning and electrospinning, respectively. Specifically, the wet-spun xetro
      microfibers demonstrated about 2- and 1.5-fold higher tensile strength compared
      with synthetic polymer polylactic acid and cross-linked collagen, respectively.
      In addition, the wet-spun xetro microfibers showed about sevenfold greater
      stiffness than collagen. Therefore, the mass production potential and greater
      mechanical properties of the xetro fiber may result in these fibers becoming a
      new promising fiber-based material for biomedical engineering.

PMID- 26297879
TI  - Bioactive properties of milk proteins in humans: A review.
AB  - Many studies have demonstrated that milk protein consumption has benefits in
      terms of promoting human health. This review assesses the intervention studies
      which have evaluated potential health enhancing effects in humans following the
      ingestion of milk proteins. The impact of milk protein ingestion has been studied
      to asses their satiating, hypotensive, antimicrobial, anti-inflammatory,
      anticancer, antioxidant and insulinotropic properties as well as their impact on
      morphological modifications (e.g., muscle and fat mass) in humans. Consistent
      health promoting effects appear to have been observed in certain instances (i.e.,
      muscle protein synthesis, insulinotropic and hypotensive activity). However,
      controversial outcomes have also been reported (i.e., antimicrobial, anti
      inflammatory, anticancer and antioxidant properties). Several factors including
      interindividual differences, the timing of protein ingestion as well as the
      potency of the active components may explain these differences. In addition,
      processing conditions have been reported, in certain instances, to affect milk
      protein structure and therefore modify their bioactive potential. It is thought
      that the health promoting properties of milk proteins are linked to the release
      of bioactive peptides (BAPs) during gastrointestinal digestion. There is a need
      for further research to develop a more in-depth understanding on the possible
      mechanisms involved in the observed physiological effects. In addition, more
      carefully controlled and appropriately powered human intervention studies are
      required to demonstrate the health enhancing properties of milk proteins in
      humans. 

PMID- 26297880
TI  - Leptin receptor expressing neurons express phosphodiesterase-3B (PDE3B) and
      leptin induces STAT3 activation in PDE3B neurons in the mouse hypothalamus.
AB  - Leptin signaling in the hypothalamus is critical for normal food intake and body
      weight regulation. Cumulative evidence suggests that besides the signal
      transducer and activator of transcription-3 (STAT3) pathway, several non-STAT3
      pathways including the phosphodiesterase-3B (PDE3B) pathway mediate leptin
      signaling in the hypothalamus. We have shown that PDE3B is localized in various
      hypothalamic sites implicated in the regulation of energy homeostasis and that
      the anorectic and body weight reducing effects of leptin are mediated by the
      activation of PDE3B. It is still unknown if PDE3B is expressed in the long form
      of the leptin-receptor (ObRb)-expressing neurons in the hypothalamus and whether
      leptin induces STAT3 activation in PDE3B-expressing neurons. In this study, we
      examined co-localization of PDE3B with ObRb neurons in various hypothalamic
      nuclei in ObRb-GFP mice that were treated with leptin (5mg/kg, ip) for 2h.
      Results showed that most of the ObRb neurons in the arcuate nucleus (ARC, 93%),
      ventromedial nucleus (VMN, 94%), dorsomedial nucleus (DMN, 95%), ventral
      premammillary nucleus (PMv, 97%) and lateral hypothalamus (LH, 97%) co-expressed
      PDE3B. We next examined co-localization of p-STAT3 and PDE3B in the hypothalamus
      in C57BL6 mice that were treated with leptin (5mg/kg, ip) for 1h. The results
      showed that almost all p-STAT3 positive neurons in different hypothalamic nuclei
      including ARC, VMN, DMN, LH and PMv areas expressed PDE3B. These results suggest
      the possibility for a direct role for the PDE3B pathway in mediating leptin
      action in the hypothalamus. 

PMID- 26297881
TI  - Transcriptome analysis to identify genes for peptides and proteins involved in
      immunity and reproduction from male accessory glands and ejaculatory duct of
      Bactrocera dorsalis.
AB  - In the male reproductive system of insects, the male accessory glands and
      ejaculatory duct (MAG/ED) are important organs and their primary function is to
      enhance the fertility of spermatozoa. Proteins secreted by the MAG/ED are also
      known to induce post-mating changes and immunity responses in the female insect.
      To understand the gene expression profile in the MAG/ED of the oriental fruit fly
      Bactrocera dorsalis (Hendel), that is an important pest in fruits, we performed
      an Illumina-based deep sequencing of mRNA. This yielded 54,577,630 clean reads
      corresponding to 4.91Gb total nucleotides that were assembled and clustered to
      30,669 unigenes (average 645bp). Among them, 20,419 unigenes were functionally
      annotated to known proteins/peptides in Gene Orthology, Clusters of Orthologous
      Groups, Kyoto Encyclopedia of Genes and Genomes pathway databases. Typically,
      many genes were involved in immunity and these included microbial recognition
      proteins and antimicrobial peptides. Subsequently, the inducible expression of
      these immunity-related genes was confirmed by qRT-PCR analysis when insects were
      challenged with immunity-inducible factors, suggesting their function in
      guaranteeing fertilization success. Besides, we identified some important
      reproductive genes such as juvenile hormone- and ecdysteroid-related genes in
      this de novo assembly. In conclusion, this transcriptomic sequencing of B.
      dorsalis MAG/ED provides insights to facilitate further functional research of
      reproduction, immunity and molecular evolution of reproductive proteins in this
      important agricultural pest.

PMID- 26297882
TI  - Homozygous deletion of TRMT10A as part of a contiguous gene deletion in a
      syndrome of failure to thrive, delayed puberty, intellectual disability and
      diabetes mellitus.
AB  - Two recent reports describe a new syndrome of intellectual disability, short
      stature, microcephaly, and young onset diabetes or disturbed glucose metabolism
      in association with inactivating mutations in the TRMT10A gene. We investigated
      the clinical spectrum presented by a 17-year-old female with a homozygous
      contiguous gene deletion involving the TRMT10A gene. From infancy, she presented
      with failure to thrive and microcephaly. Puberty was characterized by a slow and
      an inconsistent course of progression. Concomitantly, gonadotropin levels
      fluctuated between low and high levels which were compatible with gonadal
      failure. Unlike the previous reports, the patient had ketoacidosis at onset of
      diabetes and islet cell autoantibodies. Nevertheless, glycemic control was
      excellent (HbA1C 5.0%-6.2%). RT-PCR and Western blot analysis demonstrated a
      complete abolishment of TRMT10A mRNA and its translated protein. In order to
      elucidate the nature of diabetes in this patient, endogenous insulin secretion
      and glycemic control were evaluated by a glucagon stimulation test and continuous
      glucose monitoring both during insulin treatment and off therapy. Endogenous
      insulin secretion still persisted 22 months after onset of diabetes and
      relatively normal glucose levels were kept over 3 days without insulin treatment.
      The fluctuating course of puberty and diabetes may reflect intermittent apoptotic
      damages due to sensitization of the relevant cells to various stress agents in
      the absence of functional TRMT10A.

PMID- 26297883
TI  - Fluoride gel supplemented with sodium hexametaphosphate reduces enamel erosive
      wear in situ.
AB  - OBJECTIVE: This study evaluated the effect of fluoride gels, supplemented or not
      with sodium hexametaphosphate (HMP), on enamel erosive wear in situ. METHODS:
      Twelve healthy volunteers wore palatal appliances containing four bovine enamel
      discs. Subjects were randomly allocated into four experimental phases (double
      blind, crossover protocol) according to the gels: Placebo (no fluoride or HMP),
      1% NaF, 2% NaF, and 1% NaF+9% HMP. Enamel discs were selected after polishing and
      surface hardness analysis, and treated only once with the respective gels prior
      to each experimental phase. Erosion (ERO) was performed by extra-oral immersion
      of the appliance in 0.05M citric acid, pH 3.2 (four times/day, five minutes each,
      5 days). Additional abrasion (ERO+ABR) was produced on only two discs by
      toothbrushing with fluoridated dentifrice after ERO (four times/day, 30s, 5
      days). The specimens were submitted to profilometry and hardness analysis. The
      results were analyzed by two-way ANOVA and the Student-Newman-Keuls test
      (p<0.05). RESULTS: The 1% NaF+9% HMP gel promoted significantly lower enamel wear
      for ERO compared to the other groups, being statistically lower than 1% NaF and
      Placebo for ERO+ABR. Similarly, the lowest values of integrated lesion area were
      found for 1% NaF+9% HMP and 2% NaF, respectively, for ERO and ERO+ABR.
      CONCLUSION: The addition of HMP to the 1% NaF gel promoted greater protective
      effect against ERO and ERO+ABR compared to the 1% NaF gel, achieving similar
      protective levels to those seen for the 2% NaF gel. CLINICAL SIGNIFICANCE: Gel
      containing 1% NaF+9% HMP showed a high anti-erosive potential, being a safer
      alternative when compared to a conventional 2% NaF gel.

PMID- 26297884
TI  - Incorporation of fibrin into a collagen-glycosaminoglycan matrix results in a
      scaffold with improved mechanical properties and enhanced capacity to resist cell
      mediated contraction.
AB  - Fibrin has many uses as a tissue engineering scaffold, however many in vivo
      studies have shown a reduction in function resulting from the susceptibility of
      fibrin to cell-mediated contraction. The overall aim of the present study was to
      develop and characterise a reinforced natural scaffold using fibrin, collagen and
      glycosaminoglycan (FCG), and to examine the cell-mediated contraction of this
      scaffold in comparison to fibrin gels. Through the use of an injection loading
      technique, a homogenous FCG scaffold was developed. Mechanical testing showed a
      sixfold increase in compressive modulus and a thirtyfold increase in tensile
      modulus of fibrin when reinforced with a collagen-glycosaminoglycan backbone
      structure. Human vascular smooth muscle cells (vSMCs) were successfully
      incorporated into the FCG scaffold and demonstrated excellent viability over 7
      days, while proliferation of these cells also increased significantly. VSMCs were
      seeded into both FCG and fibrin-only gels at the same seeding density for 7 days
      and while FCG scaffolds did not demonstrate a reduction in size, fibrin-only gels
      contracted to 10% of their original diameter. The FCG scaffold, which is composed
      of natural biomaterials, shows potential for use in applications where
      dimensional stability is crucial to the functionality of the tissue. STATEMENT OF
      SIGNIFICANCE: Fibrin is a versatile scaffold for tissue engineering applications,
      but its weak mechanical properties leave it susceptible to cell-mediated
      contraction, meaning the dimensions of the fibrin construct will change over
      time. We have reinforced fibrin with a collagen glycosaminoglycan matrix and
      characterised the mechanical properties and bioactivity of the reinforced fibrin
      (FCG). This is the first scaffold manufactured from all naturally derived
      materials that resists cell-mediated contraction. In fact, over 7 days, the FCG
      scaffold fully resisted cell-mediated contraction of vascular smooth muscle
      cells. This FCG scaffold has many potential applications where natural scaffold
      materials can encourage regeneration.

PMID- 26297885
TI  - 3D patterned substrates for bioartificial blood vessels - The effect of hydrogels
      on aligned cells on a biomaterial surface.
AB  - The optimal bio-artificial blood vessel construct is one that has a compliant
      tubular core with circumferentially aligned smooth muscle cells (SMCs). Obtaining
      this well-aligned pattern of SMCs on a scaffold is highly beneficial as this
      cellular orientation preserves the SMC contractile phenotype. We used 3D
      patterning to create channels on a polycaprolactone (PCL) scaffold; SMCs were
      then found to be aligned within the microchannels. To preserve this alignment,
      and to provide a protective coating that could further incorporate cells, we
      evaluated the use of two hydrogels, one based on poly(ethylene glycol) diacrylate
      (PEGDA) and the other based on gelatin. Hydrogels were either physically coated
      on the PCL surfaces or covalently linked via suitable surface modification of
      PCL. For covalent immobilization of PEGDA hydrogel, alkene groups were introduced
      on PCL, while for gelatin covalent linkage, serum proteins were introduced. It
      is, however, crucial that the hydrogel coating does not disrupt the cellular
      patterning and distribution. We show in this work that both the process of
      coating as well as the nature of the coating are critical to preservation of the
      aligned SMCs. The covalent coating methods involving the crosslinking of
      hydrogels with the surface of PCL films promoted hydrogel retention time on the
      film as compared with physical deposition. Furthermore, subsequent hydrogel
      degradation is affected by the components of the cell culture medium, hinting at
      a possible route to in vivo biodegradation. STATEMENT OF SIGNIFICANCE: Surface
      features control cellular orientation and subsequently influence their
      functionality, a useful effect for cellularized biomedical devices. Such devices
      also can benefit from protective and cell friendly hydrogel coatings. However,
      literature is lacking on the fate of cells that have endured hydrogel coating
      whilst orientated on a biomaterial surface. In particular, elucidation of the
      cells ability to remain adherent and orientated post hydrogel addition. Coating
      requires two procedures that may be deleterious to the orientated cells: the
      surface pretreatment for gel binding and the hydrogel crosslinking reaction. We
      compare transglutaminase gelatin crosslinking and UV initiated PEGDA
      crosslinking, coated onto smooth muscle cells orientated on patterned PCL
      surfaces. This original study will be of considerable use to the wider
      biomaterials community.

PMID- 26297886
TI  - Elastomeric and mechanically stiff nanocomposites from poly(glycerol sebacate)
      and bioactive nanosilicates.
AB  - Poly(glycerol sebacate) (PGS) has been proposed for tissue engineering
      applications owing to its tough elastomeric mechanical properties,
      biocompatibility and controllable degradation. However, PGS shows limited
      bioactivity and thus constraining its utilization for musculoskeletal tissue
      engineering. To address this issue, we developed bioactive, highly elastomeric,
      and mechanically stiff nanocomposites by covalently reinforcing PGS network with
      two-dimensional (2D) nanosilicates. Nanosilicates are ultrathin nanomaterials and
      can induce osteogenic differentiation of human stem cells in the absence of any
      osteogenic factors such as dexamethasone or bone morphogenetic proteins-2 (BMP2).
      The addition of nanosilicate to PGS matrix significantly enhances the mechanical
      stiffness without affecting the elastomeric properties. Moreover, nanocomposites
      with higher amount of nanosilicates have higher in vitro stability as determined
      by degradation kinetics. The increase in mechanical stiffness and in vitro
      stability is mainly attributed to enhanced interactions between nanosilicates and
      PGS. We evaluated the in vitro bioactivity of nanocomposite using preosteoblast
      cells. The addition of nanosilicates significantly enhances the cell adhesion,
      support cell proliferation, upregulate alkaline phosphates and mineralized matrix
      production. Overall, the combination of high mechanically stiffness and
      elastomericity, tailorable degradation profile, and the ability to promote
      osteogenic differentiation of PGS-nanosilicate can be used for regeneration of
      bone.

PMID- 26297887
TI  - Improved light-induced cell detachment on rutile TiO2 nanodot films.
AB  - Anatase TiO2 nanodot films have been found to be able to release cells under
      light illumination with excellent efficiency and safety. In the present study, we
      investigated the effects of rutile contents in TiO2 nanodot films on such light
      induced cell detachment behavior. The results showed that TiO2 nanodot films with
      different contents of rutile phase have been prepared successfully. The content
      of rutile phase increased with the increase in calcination temperature. All films
      possessed good cell adhesion but there was a decrease in cell proliferation with
      the increasing content of rutile phase. Single cell detachment assay showed that
      the films with high rutile contents (calcined at 900 degrees C and 1100 degrees
      C) showed better cell detachment performance. That was ascribed to the changes of
      the secondary structure of extracellular proteins adsorbed on the nanodot surface
      after ultraviolet (365 nm, UV365) illumination. In addition, cell sheets detached
      through UV365 illumination maintained high activity and could be further used in
      tissue engineering. The present work showed that the existence of rutile phase is
      helpful in cell detachment behavior and it could be utilized to optimize light
      induced cell detachment behavior. STATEMENT OF SIGNIFICANCE: This work discovers
      that the presence of rutile phase in TiO2 nanodot films could improve the light
      induced cell detachment behavior, although rutile phase is inferior to anatase
      phase on light induced superhydrophilicity. That strongly supported that the
      behaviors of adsorbed proteins are crucial in acquiring cell sheet with light
      illumination. In fact, the state and behavior of adsorbed protein greatly affect
      the interaction between biomaterials and living cells. Therefore, we consider
      this work is not only important in harvesting cells or cell sheets through light
      illumination, but also helpful in further understanding of interaction between
      biomaterials and cells.

PMID- 26297888
TI  - Photodynamic therapy of melanoma skin cancer using carbon dot - chlorin e6 -
      hyaluronate conjugate.
AB  - Despite wide application of photodynamic therapy (PDT) for the treatment of
      melanoma skin cancers, there are strong biomedical unmet needs for the effective
      generation of singlet oxygen after targeted delivery of photosensitizers. Here,
      we investigated a facile PDT of melanoma skin cancer using transdermal carbon dot
      - chlorine e6 - hyaluronate (Cdot-Ce6-HA) conjugates. The Cdot-Ce6-HA conjugate
      was synthesized by the coupling reaction of diaminohexane modified HA (DAH-HA)
      with the carboxylic group of Ce6. The singlet oxygen generation of Cdot-Ce6-HA
      conjugates in aqueous solution was more significant than that of free Ce6. The
      enhanced transdermal and intracellular delivery of Cdot-Ce6-HA conjugates to
      B16F10 melanoma cells in tumor model mice were corroborated by confocal
      microscopy and two-photon microscopy. The laser irradiation after topical
      treatment with Cdot-Ce6-HA conjugates resulted in complete suppression of
      melanoma skin cancers. The antitumor effect was confirmed by histological
      analysis with H&E staining and TUNEL assay for tumor apoptosis. Taken together,
      we could confirm the feasibility of Cdot-Ce6-HA conjugate for transdermal PDT of
      melanoma skin cancers. STATEMENT OF SIGNIFICANCE: To our knowledge, this is the
      first report on a facile transdermal photodynamic therapy (PDT) of melanoma skin
      cancer using carbon dot - chlorine e6 - hyaluronate (Cdot-Ce6-HA) conjugates. We
      found that the singlet oxygen generation of Cdot-Ce6-HA conjugates in aqueous
      solution was more significant than that of free Ce6. Confocal microscopy and two
      photon microscopy clearly confirmed the enhanced transdermal and intracellular
      delivery of Cdot-Ce6-HA conjugates to B16F10 melanoma cells in tumor model mice.
      Taken together, we could confirm the feasibility of Cdot-Ce6-HA conjugate for
      transdermal PDT of melanoma skin cancers.

PMID- 26297889
TI  - Classification of membrane protein types using Voting Feature Interval in
      combination with Chou's Pseudo Amino Acid Composition.
AB  - Membrane protein is a major constituent of cell, performing numerous crucial
      functions in the cell. These functions are mostly concerned with membrane
      protein's types. Initially, membrane proteins types are classified through
      traditional methods and reasonable results were obtained using these methods.
      However, due to large exploration of protein sequences in databases, it is very
      difficult or sometimes impossible to classify through conventional methods,
      because it is laborious and wasting of time. Therefore, a new powerful
      discriminating model is indispensable for classification of membrane protein's
      types with high precision. In this work, a quite promising classification model
      is developed having effective discriminating power of membrane protein's types.
      In our classification model, silent features of protein sequences are extracted
      via Pseudo Amino Acid Composition. Five classification algorithms were utilized.
      Among these classification algorithms Voting Feature Interval has obtained
      outstanding performance in all the three datasets. The accuracy of proposed model
      is 93.9% on dataset S1, 89.33% on S2 and 86.9% on dataset S3, respectively,
      applying 10-fold cross validation test. The success rates revealed that our
      proposed model has obtained the utmost outcomes than other existing models in
      literatures so far and will be played a substantial role in the fields of drug
      design and pharmaceutical industry.

PMID- 26297890
TI  - Classification of signaling proteins based on molecular star graph descriptors
      using Machine Learning models.
AB  - Signaling proteins are an important topic in drug development due to the
      increased importance of finding fast, accurate and cheap methods to evaluate new
      molecular targets involved in specific diseases. The complexity of the protein
      structure hinders the direct association of the signaling activity with the
      molecular structure. Therefore, the proposed solution involves the use of protein
      star graphs for the peptide sequence information encoding into specific
      topological indices calculated with S2SNet tool. The Quantitative Structure
      Activity Relationship classification model obtained with Machine Learning
      techniques is able to predict new signaling peptides. The best classification
      model is the first signaling prediction model, which is based on eleven
      descriptors and it was obtained using the Support Vector Machines-Recursive
      Feature Elimination (SVM-RFE) technique with the Laplacian kernel (RFE-LAP) and
      an AUROC of 0.961. Testing a set of 3114 proteins of unknown function from the
      PDB database assessed the prediction performance of the model. Important
      signaling pathways are presented for three UniprotIDs (34 PDBs) with a signaling
      prediction greater than 98.0%. 

PMID- 26297891
TI  - Systematic exchanges between nucleotides: Genomic swinger repeats and swinger
      transcription in human mitochondria.
AB  - Chargaff's second parity rule, quasi-equal single strand frequencies for
      complementary nucleotides, presumably results from insertion of repeats and
      inverted repeats during sequence genesis. Vertebrate mitogenomes escape this rule
      because repeats are counterselected: their hybridization produces loop bulges
      whose deletion is deleterious. Some DNA/RNA sequences match mitogenomes only
      after assuming one among 23 systematic nucleotide exchanges (swinger DNA/RNA:
      nine symmetric, e.g. A <-> C; and 14 asymmetric, e.g. A -> C -> G -> A). Swinger
      transformed repeats do not hybridize, escaping selection against deletions due to
      bulge formation. Blast analyses of the human mitogenome detect swinger repeats
      for all 23 swinger types, more than in randomized sequences with identical length
      and nucleotide contents. Mean genomic swinger repeat lengths increase with
      observed human swinger RNA frequencies: swinger repeat and swinger RNA
      productions appear linked, perhaps by swinger RNA retrotranscription. Mean
      swinger repeat lengths are proportional to reading frame retrievability, post
      swinger transformation, by the natural circular code. Genomic swinger repeats
      confirm at genomic level, independently of swinger RNA detection, occurrence of
      swinger polymerizations. They suggest that repeats, and swinger repeats in
      particular, contribute to genome genesis.

PMID- 26297892
TI  - Alpha2beta1 integrin in cancer development and chemoresistance.
AB  - Extracellular matrix, via its receptors the integrins, has emerged as a crucial
      factor in cancer development. The alpha2beta1 integrin is a major collagen
      receptor that is widely expressed and known to promote cell migration and control
      tissue homeostasis. Growing evidence suggests that it can be a key pathway in
      cancer. Recent studies have shown that alpha2beta1 integrin is a regulator of
      cancer metastasis either by promoting or inhibiting the dissemination process of
      cancer cells. The alpha2beta1 integrin signaling can also enhance tumor
      angiogenesis. Emerging evidence supports a role for alpha2beta1 integrin in
      cancer chemoresistance especially in hematological malignancies originating from
      the T cell lineage. In addition, alpha2beta1 integrin has been associated with
      cancer stem cells. In this review, we will discuss the complex role of
      alpha2beta1 integrin in these processes. Collagen is a major matrix protein of
      the tumor microenvironment and thus, understanding how alpha2beta1 integrin
      regulates cancer pathogenesis is likely to lead to new therapeutic approaches and
      agents for cancer treatment. 

PMID- 26297893
TI  - Synaptic changes in GABAA receptor expression in the thalamus of the stargazer
      mouse model of absence epilepsy.
AB  - Absence seizures are known to result from disturbances within the cortico
      thalamocortical network, which remains partially synchronous under normal
      conditions but switches to a state of hypersynchronicity and hyperexcitability
      during absence seizures. There is evidence to suggest that impaired GABAergic
      inhibitory function within the thalamus could contribute to the generation of
      hypersynchronous oscillations in some animal models of absence epilepsy.
      Recently, we demonstrated region-specific alterations in the tissue expression
      level of GABAA receptors (GABA(A)Rs) alpha1 and beta2 subunits within the
      thalamus of the stargazer mouse model of absence epilepsy. In the present study
      we investigated whether changes in these subunits also occur at synapses in the
      ventral posterior (VP) complex where they are components of phasic GABA(A)R
      receptors. Postembedding immunogold cytochemistry and electron microscopy were
      used to analyze the relative synaptic expression of alpha1 and beta2 subunits in
      the VP thalamic region in epileptic stargazer mice compared to their non
      epileptic littermates. We show that there is a significant increase in expression
      of alpha1 and beta2 subunits (53.6% and 45.8%, respectively) at synapses in the
      VP region of stargazers, indicative of an increase in phasic GABA(A)Rs at
      thalamocortical (TC) relay neurons. Furthermore, we investigated whether tissue
      expression of GABA(A)R subunits alpha4 and delta, which constitute part of tonic
      GABA(A)Rs in the VP region, is altered in the stargazer mouse. Semi-quantitative
      Western blotting showed a significant increase in GABA(A)R alpha4 and delta
      subunits in the VP region of stargazer thalamus, which would indicate an increase
      in tonic GABA(A)R expression. Our findings show that there are changes in the
      levels of both phasic and tonic GABA(A)Rs in the VP thalamus; altered GABAergic
      inhibition within the VP could be one of many mechanisms contributing to the
      generation of absence seizures in this model.

PMID- 26297894
TI  - Cardiovascular and single-unit responses to L-glutamate injection into the
      posterior insular cortex in rat.
AB  - The insular cortex in rat is a longitudinal strip that runs along the rostral
      half of the rhinal fissure. The previous studies showed connections between the
      posterior insular cortex (PIC) and some major cardiovascular centers. Based on
      the stimulation site, electrical or chemical stimulation of the PIC induced an
      increase or a decrease in blood pressure (BP) and heart rate (HR). There is no
      report of simultaneous cardiovascular and single-unit recording microinjection of
      Glut in the PIC. In this study, L-glutamate was microinjected into the PIC of
      urethane anesthetized rats and arterial pressure, HR and single-unit responses
      were recorded simultaneously. Also the response of the neurons to baroreceptor
      activation was explored. Glut produced five types of long oscillatory, pressor,
      depressor, bradycardic and tachycardic cardiovascular responses, with no
      association between pressure and HR responses. We also observed five single-unit
      responses, consisting of short excitatory, long oscillatory, excitatory,
      inhibitory and mixed responses. There was an association between oscillation in
      BP and in single-unit response. There were some differences between the two sides
      especially for single-unit responses. In conclusion, there were five types of
      cardiovascular and five types of single-unit responses, to Glut microinjection
      into PIC, from which three types were correlated. The left side of the PIC is
      involved more in the cardiovascular functions. These data along with the fact
      that most recorded neurons responded to baroreceptor activation, might imply the
      presence of feedback systems in the PIC, producing irregularity in BP and HR.

PMID- 26297895
TI  - Effect of parasitic infection on dopamine biosynthesis in dopaminergic cells.
AB  - Infection by the neurotropic agent Toxoplasma gondii alters rodent behavior and
      can result in neuropsychiatric symptoms in humans. Little is understood regarding
      the effects of infection on host neural processes but alterations to dopaminergic
      neurotransmission are implicated. We have previously reported elevated levels of
      dopamine (DA) in infected dopaminergic cells however the involvement of the host
      enzymes and fate of the produced DA were not defined. In order to clarify the
      effects of infection on host DA biosynthetic enzymes and DA packaging we examined
      enzyme levels and activity and DA accumulation and release in T. gondii-infected
      neurosecretory cells. Although the levels of the host tyrosine hydroxylase (TH)
      and DOPA decarboxylase and AADC (DDC) did not change significantly in infected
      cultures, DDC was found within the parasitophorous vacuole (PV), the vacuolar
      compartment where the parasites reside, as well as in the host cytosol in
      infected dopaminergic cells. Strikingly, DDC was found within the intracellular
      parasite cysts in infected brain tissue. This finding could provide some
      explanation for observations of DA within tissue cysts in infected brain as a
      parasite-encoded enzyme with TH activity was also localized within tissue cysts.
      In contrast, cellular DA packaging appeared unchanged in single-cell
      microamperometry experiments and only a fraction of the increased DA was
      accessible to high potassium-induced release. This study provides some
      understanding of how this parasite produces elevated DA within dopaminergic cells
      without the toxic ramifications of free cytosolic DA. The mechanism for synthesis
      and packaging of DA by T. gondii-infected dopaminergic cells may have important
      implications for the effects of chronic T. gondii infection on humans and
      animals. 

PMID- 26297896
TI  - In vitro validation of effects of BDNF-expressing mesenchymal stem cells on
      neurodegeneration in primary cultured neurons of APP/PS1 mice.
AB  - Alzheimer's disease (AD), the most common type of dementia, is characterized by
      the presence of senile plaques, neurofibrillary tangles, and neuronal loss in
      defined regions of the brain including the hippocampus and cortex.
      Transplantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) offers a
      safe and potentially effective tool for treating neurodegenerative disorders.
      However, the therapeutic effects of BM-MSCs on AD pathology remain unclear and
      their mechanisms at cellular and molecular levels still need to be addressed. In
      this study, we developed a unique neuronal culture made from 5xFAD mouse, an
      APP/PS1 transgenic mouse model (FAD neurons) to investigate progressive
      neurodegeneration associated with AD pathology and efficacy of brain-derived
      neurotrophic factor expressing-MSCs (BDNF-MSCs). Analyses of the expression of
      brain-derived neurotrophic factor (BDNF), synaptic markers and survival/apoptotic
      signals indicate that pathological features of cultured neurons made from these
      mice accurately mimic AD pathology, suggesting that our protocol provided a valid
      in vitro model of AD. We also demonstrated amelioration of AD pathology by MSCs
      in vitro when these FAD neurons were co-cultured with MSCs, a paradigm that
      mimics the in vivo environment of post-transplantation of MSCs into damaged
      regions of brains. To overcome failed delivery of BDNF to the brain and to
      enhance MSCs releasing BDNF effect, we created BDNF-MSCs and found that MSCs
      protection was enhanced by BDNF-MSCs. This protection was abolished by BDNF
      blocking peptides, suggesting that BDNF supply from BDNF-MSCs was enough to
      prevent AD pathology. 

PMID- 26297897
TI  - Effects of early-life stress on cognitive function and hippocampal structure in
      female rodents.
AB  - We tested the effect of early-life stress (ELS) - 24h maternal deprivation (MD)
      at postnatal day (PND) 3 - on cognitive performance and hippocampal structure in
      12-17-week-old female rats. Behavioral performance was examined in: the Elevated
      Plus Maze, as an index for general anxiety; the rodent Iowa gambling test,
      probing reward-based decision making; and the object recognition and object-in
      location task, to assess non-stressful contextual memory performance. We further
      determined hippocampal dentate gyrus (DG) volume and cell density as well as
      adult proliferation and neurogenesis rates. Half of the rats was treated with the
      glucocorticoid receptor antagonist mifepristone during a critical pre-pubertal
      developmental window (PNDs 26-28), in an attempt to ameliorate the potentially
      adverse behavioral consequences of ELS. Neither MD nor treatment with the
      glucocorticoid antagonist affected behavioral performance of the females in any
      of the tasks. Also, DG structure, proliferation and neurogenesis were not
      different between the groups. Lack of structural differences and a behavioral
      phenotype in non-stressful hippocampus dependent learning tasks fits with the
      lack of phenotype generally reported after ELS in female but less so in male
      rodents. As evident from an extensive literature review, female and male animals
      appear to respond more similarly to early-life adversity when tested in anxiety
      related tasks. This agrees with recent findings in humans suggesting that females
      may be relatively resilient to the structural/hippocampal effects of childhood
      maltreatment, but not to the anxiety and mood-related psychopathology for which
      childhood maltreatment is considered a risk factor.

PMID- 26297898
TI  - Photothrombosis combined with thrombin injection establishes a rat model of
      cerebral venous sinus thrombosis.
AB  - OBJECTIVE: Cerebral venous sinus thrombosis (CVST) is a rare but life-threatening
      disease and an animal model for in-depth study of CVST is needed. This study
      aimed to develop a rat model suitable for studying clinically relevant aspects of
      CVST and investigating its dynamic pathophysiological changes during a 7-day
      period. METHOD: A photothrombosis method was used to create a rat sinus-vein
      thrombosis model. A spot size-adjustable Diode Pumped Solid State laser (DPSS)
      combined with thrombin injection occluded the rostral and caudal superior
      sagittal sinus (SSS). The model was used to evaluate pathophysiological changes
      at different time points over 7 days. Evans Blue dye injection was used to detect
      alterations in blood-brain barrier (BBB) permeability. Brain water content was
      also measured. Moreover, we examined changes in brain infarct volume,
      neurological function, as well as histology after induction of CVST. RESULT: CVST
      in rats significantly altered BBB permeability, consistent with the development
      of brain edema. It was accompanied by an increase in brain infarct volume and
      deficits in neurological function that began on day 1, peaked on day 2, and
      typically improved by day 7 due to the neuroprotective effects of angiogenesis
      and gliocyte proliferation. CONCLUSION: In this study, we describe a rat model
      that produces clinically relevant pathophysiology and pathology that will
      facilitate evaluation of therapeutic regimens for CVST. Furthermore, our results
      indicate a period of optimal clinical intervention for patients with CVST, which
      may reduce the probability of dependency and death.

PMID- 26297900
TI  - Psychosocial aspects of ejaculatory dysfunction and male reproduction.
AB  - This article provides a summary of the biopsychosocial model and the assessment
      and treatment of male sexual dysfunction as manifested in cases of infertility.
      In couples trying to get pregnant, a unique set of psychosocial and behavioral
      changes may evolve that directly interferes with a couple's usual pattern of
      sexual behavior, resulting in sexual dysfunction. The unique set of changes is
      discussed and how these changes impact on erectile and ejaculatory function.
      Strategies for assessing and managing male sexual dysfunction that compromise
      fertility are reviewed. 

PMID- 26297899
TI  - Molecular and functional changes in glucokinase expression in the brainstem
      dorsal vagal complex in a murine model of type 1 diabetes.
AB  - Glucose concentration changes in the nucleus tractus solitarius (NTS) affect
      visceral function and metabolism by influencing central vagal circuits,
      especially inhibitory, GABAergic NTS neurons. Acutely elevated glucose can alter
      NTS neuron activity, and prolonged hyperglycemia and hypoinsulemia in animal
      models of type 1 diabetes results in plasticity of neural responses in the NTS.
      NTS neurons contributing to metabolic regulation therefore act as central glucose
      sensors and are functionally altered in type 1 diabetes. Glucokinase (GCK)
      mediates cellular utilization of glucose, linking increased glucose concentration
      to excitability changes mediated by ATP-sensitive K(+) channels (KATP). Using
      quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), Western
      blot, and in vitro electrophysiology, we tested the hypothesis that changes in
      GCK expression in the NTS accompany the development of diabetes symptoms in the
      streptozotocin (STZ)-treated mouse model of type 1 diabetes. After several days
      of hyperglycemia in STZ-treated mice, RNA expression of GCK, but not Kir6.2 or
      SUR1, was decreased versus controls in the dorsal vagal complex.
      Electrophysiological recordings in vitro indicated that neural responses to acute
      hyperglycemia, and synaptic responsiveness to blockade of GCK with glucosamine,
      were attenuated in GABAergic NTS neurons from STZ-treated mice, consistent with
      reduced molecular and functional expression of GCK in the vagal complex of
      hyperglycemic, STZ-treated mice. Altered autonomic responses to glucose in type 1
      diabetes may therefore involve reduced functional GCK expression in the dorsal
      vagal complex. 

PMID- 26297901
TI  - Association between previously unknown connective tissue disease and subclinical
      hypothyroidism diagnosed during first trimester of pregnancy.
AB  - OBJECTIVE: To investigate the presence of autoimmune rheumatic disorders among
      women with autoimmune thyroid disorders diagnosed during the first trimester of
      pregnancy and subsequent pregnancy outcomes. DESIGN: Case-control study. SETTING:
      Tertiary obstetric and gynecologic center. PATIENT(S): Pregnant women in the
      first trimester of pregnancy. INTERVENTION(S): Clinical, laboratory,
      ultrasonographic evaluations. MAIN OUTCOME MEASURE(S): Thyroid-stimulating
      hormone (TSH) level; antibodies against thyroperoxidase, thyroid globulin and TSH
      receptor detection; screening for rheumatic symptoms and antinuclear antibodies
      (ANA); uterine artery pulsatility index evaluation; pregnancy complication onset.
      RESULT(S): Out of 3,450 women enrolled, 106 (3%) were diagnosed with autoimmune
      thyroid disorders. ANA were present in 18 (16.9%) of 106 cases and 26 (12.6%) of
      206 controls. Of the cases, 28 (26.4%) of 106 reported rheumatic symptoms, 5 of
      these were diagnosed with Sjogren syndrome or with undefined connective tissue
      disease. Autoimmune thyroid diseases are statistically significantly associated
      with a higher risk of preeclampsia, fetal growth restriction, and overall
      pregnancy complications compared with controls, with a higher uterine artery
      pulsatility index, suggesting a defective placentation in thyroid disorders. The
      effect of ANA-positivity on moderate/severe adverse pregnancy outcomes was
      statistically significant among the patients with thyroid disorders (9 of 18 as
      compared to 8 of 88, odds ratio 9.65; 95% confidence interval, 2.613-7.81).
      CONCLUSION(S): Connective tissue diseases are frequently associated with
      autoimmune thyroid disorders diagnosed during the first trimester of pregnancy.
      Thyroid autoimmunity and ANA positivity independently increased the risk of
      adverse pregnancy outcomes.

PMID- 26297902
TI  - Endoscopic surgery of the orbital apex: Outcomes and emerging techniques.
AB  - OBJECTIVES/HYPOTHESIS: To review our experience with endoscopic orbital apex
      surgery. STUDY DESIGN: Retrospective review. METHODS: All cases with Current
      Procedural Terminology codes for endoscopic orbital decompression between 2002
      and 2011 at two institutions were reviewed. Patients with a diagnosis of Graves
      orbitopathy or an orbital complication of sinusitis were excluded. Presenting
      symptoms, lesion location, pathology, surgical outcomes, and complications were
      examined. RESULTS: A total of 27 patients were identified. Seventeen (63%) of the
      patients were men, and the average age was 56 (range = 14-82) years. Eighteen
      patients had primary orbital apex lesions, and nine patients had sinonasal
      lesions that predominantly involved the medial orbital apex. The lesions were
      found to be on the right in 59% of cases. The etiologies include benign (40.7%),
      malignant (44%), infectious (7.4%), and metastatic (7.4%) lesions. Obtaining a
      pathologic diagnosis was successful endoscopically in all but two (7.4%)
      patients, both with lateral lesions. The two-surgeon, four-handed technique and
      intraoperative image guidance employing fused computed tomography/magnetic
      resonance imaging were used in the majority of intraconal cases. Complications
      occurred in three patients (11%) and included myocardial infarction, deep venous
      thrombosis, and vision loss. There were no cerebrospinal fluid leaks or
      postoperative hemorrhages. Notably, vision remained stable or improved in all but
      one patient (3.7% risk of vision decline). Average follow-up was 4 years (range =
      1 month-8 years). CONCLUSIONS: The endoscopic approach to the orbit apex offers
      significant advantages over traditional external approaches, and should be the
      preferred approach for all medial and inferior lesions. A two-surgeon multihanded
      technique can help facilitate difficult cases.

PMID- 26297903
TI  - Genetics of long-term treatment outcome in bipolar disorder.
AB  - Bipolar disorder (BD) shows one of the strongest genetic predispositions among
      psychiatric disorders and the identification of reliable genetic predictors of
      treatment response could significantly improve the prognosis of the disease. The
      present study investigated genetic predictors of long-term treatment-outcome in
      723 patients with BD type I from the STEP-BD (Systematic Treatment Enhancement
      Program for Bipolar Disorder) genome-wide dataset. BD I patients with >6months of
      follow-up and without any treatment restriction (reflecting a natural setting
      scenario) were included. Phenotypes were the total and depressive episode rates
      and the occurrence of one or more (hypo)manic/mixed episodes during follow-up.
      Quality control of genome-wide data was performed according to standard criteria
      and linear/logistic regression models were used as appropriate under an additive
      hypothesis. Top genes were further analyzed through a pathway analysis. Genes
      previously involved in the susceptibility to BD (DFNB31, SORCS2, NRXN1, CNTNAP2,
      GRIN2A, GRM4, GRIN2B), antidepressant action (DEPTOR, CHRNA7, NRXN1), and mood
      stabilizer or antipsychotic action (NTRK2, CHRNA7, NRXN1) may affect long-term
      treatment outcome of BD. Promising findings without previous strong evidence were
      TRAF3IP2-AS1, NFYC, RNLS, KCNJ2, RASGRF1, NTF3 genes. Pathway analysis supported
      particularly the involvement of molecules mediating the positive regulation of
      MAPK cascade and learning/memory processes. Further studies focused on the
      outlined genes may be helpful to provide validated markers of BD treatment
      outcome. 

PMID- 26297904
TI  - Integrated continuous biomanufacturing: A new paradigm for biopharmaceutical
      production.

PMID- 26297905
TI  - Complete genome of the potential thermozyme producer Anoxybacillus gonensis G2(T)
      isolated from the Gonen hot springs in Turkey.
AB  - Anoxybacillus gonensis type strain G2(T) (=NCIMB 13,933(T) =NCCB 100040(T)) has
      been isolated from the Gonen hot springs in Turkey. This strain produces a number
      of well-studied, biotechnologically important enzymes, including xylose
      isomerase, carboxylesterase, and fructose-1,6-bisphosphate aldolase. In addition,
      this strain is an excellent candidate for the bioremediation of areas with heavy
      metal pollution. Here, we present a high-quality, annotated, complete genome of
      A. gonensis G2(T). Furthermore, this report provides insights into several novel
      enzymes of strain G2(T) and their potential industrial applications. 

PMID- 26297906
TI  - Complete genome sequence of Bacillus amyloliquefaciens L-S60, a plant growth
      promoting and antifungal bacterium.
AB  - Bacillus amyloliquefaciens L-S60, a gram-positive plant-associated bacterium,
      which could stimulate plant growth and shows strong antifungal function, was
      isolated from the turfy soil in Beijing, China. The genome of B.
      amyloliquefaciens L-S60 comprises a 3903,017bp long circular chromosome that
      consists of 3909 protein-coding genes and 117 RNA genes. Based on genomic
      analysis, we identified gene clusters responsible for the biosynthesis of
      numerous bioactive metabolites with well-established in-vitro activity such as
      surfactin, iturin and fengycins. Additionally, we also found functionally related
      genes in the genome of L-S60, which play key roles in the process of plant growth
      promotion hormone secretion, biofilm formation and volatile compounds production.

PMID- 26297907
TI  - Whole genome sequence typing and microarray profiling of nasal and blood stream
      methicillin-resistant Staphylococcus aureus isolates: Clues to phylogeny and
      invasiveness.
AB  - Hospital-associated methicillin-resistant Staphylococcus aureus (MRSA) infections
      are frequently caused by predominant clusters of closely related isolates that
      cannot be discriminated by conventional diagnostic typing methods. Whole genome
      sequencing (WGS) and DNA microarray (MA) now allow for better discrimination
      within a prevalent clonal complex (CC). This single center exploratory study aims
      to distinguish invasive (blood stream infection) and non-invasive (nasal
      colonization) MRSA isolates of the same CC5 into phylogenetic- and virulence
      associated genotypic subgroups by WGS and MA. A cohort of twelve blood stream and
      fifteen nasal MRSA isolates of CC5 (spa-types t003 and t504) was selected.
      Isolates were propagated at the same period of time from unrelated patients
      treated at the University of Saarland Medical Center, Germany. Rooted phylotyping
      based on WGS with core-genome single nucleotide polymorphism (SNP) analysis
      revealed two local clusters of closely related CC5 subgroups (t504 and Clade1
      t003) which were separated from other local t003 isolates and from unrelated CC5
      MRSA reference isolates of German origin. Phylogenetic subtyping was not
      associated with invasiveness when comparing blood stream and nasal isolates.
      Clustering based on MA profiles was not concordant with WGS phylotyping, but MA
      profiles may identify subgroups of isolates with nasal and blood stream origin.
      Among the new putative virulence associated genes identified by WGS, the
      strongest association with blood stream infections was shown for ebhB mutants.
      Analysis of the core-genome together with the accessory genome enables subtyping
      of closely related MRSA isolates according to phylogeny and presumably also to
      the potential virulence capacity of isolates. 

PMID- 26297908
TI  - Differential activation of ER stress pathways in myelinating cerebellar tracts.
AB  - Myelin production during brain development requires an increase in membrane
      protein and lipid production in oligodendrocytes and this primarily occurs in the
      endoplasmic reticulum (ER), an organelle which initiates the Unfolded Protein
      Response (UPR) when under stress. We hypothesise that the UPR is activated in
      white matter tracts during myelination in order to expand the ER capacity of
      oligodendrocytes. Using early and late stage markers, critical myelination time
      points were identified by immunohistochemistry in developing rat cerebellum.
      These were correlated to peaks in ER stress signalling by staining for activated
      UPR transducers (pIRE1, ATF6 and pPERK) and associated downstream molecules
      (peIF2alpha, PDI, GRP78, GRP94, CHOP and calreticulin) in cerebellar tracts III
      and IV. Gene expression in developing cerebellum was assessed by qPCR. Actively
      myelinating tracts were shown to have differential expression of pIRE1, PERK and
      ATF6 as well as UPR targets GRP94, GRP78 and PDI. Activated pIRE1-positive cells
      were widespread at P14 and P17 and at significantly higher numbers during
      myelination than at other stages. Nuclear-localised ATF6 (indicative of the
      active transcription factor) peaked at P10, concurrent with the initial phase of
      myelination. The percentage of cells positive for pPERK was less than 1% at
      postnatal ages but increased significantly in adult tissue. The downstream
      targets GRP78, GRP94 and PDI were significantly up-regulated at P17 compared to
      P7 and remained significantly elevated in adults. The majority of cells positive
      for these markers and ATF6 were oligodendrocytes as confirmed by dual-labelling.
      Although gene expression in the cerebellum for GRP78, GRP94 and PDI did not
      change significantly over time, ATF6 and XBP1s both showed significant fold
      changes between early and late timepoints. This data helps promote understanding
      of events occurring during developmental myelination and may have implications
      for the development of reparative treatments in diseases such as multiple
      sclerosis. 

PMID- 26297909
TI  - FK866 compromises mitochondrial metabolism and adaptive stress responses in
      cultured cardiomyocytes.
AB  - AIM: FK866 is an inhibitor of the NAD(+) synthesis rate-limiting enzyme
      nicotinamide phosphoribosyltransferase (NAMPT). Using FK866 to target NAD(+)
      synthesis has been proposed as a treatment for inflammatory diseases and cancer.
      However, use of FK866 may pose cardiovascular risks, as NAMPT expression is
      decreased in various cardiomyopathies, with low NAD(+) levels playing an
      important role in cardiovascular disease progression. In addition, low NAD(+)
      levels are associated with cardiovascular risk conditions such as aging,
      dyslipidemia, and type II diabetes mellitus. The aim of this work was to study
      the effects of FK866-induced NAD(+) depletion on mitochondrial metabolism and
      adaptive stress responses in cardiomyocytes. METHODS AND RESULTS: FK866 was used
      to deplete NAD(+) levels in cultured rat cardiomyocytes. Cell viability,
      mitochondrial metabolism, and adaptive responses to insulin, norepinephrine, and
      H2O2 were assessed in cardiomyocytes. The drop in NAD(+) induced by FK866
      decreased mitochondrial metabolism without changing cell viability. Insulin
      stimulated Akt phosphorylation, glucose uptake, and H2O2-survival were
      compromised by FK866. Glycolytic gene transcription was increased, whereas
      cardiomyocyte hypertrophy induced by norepinephrine was prevented. Restoring
      NAD(+) levels via nicotinamide mononucleotide administration reestablished
      mitochondrial metabolism and adaptive stress responses. CONCLUSION: This work
      shows that FK866 compromises mitochondrial metabolism and the adaptive response
      of cardiomyocytes to norepinephrine, H2O2, and insulin.

PMID- 26297910
TI  - Cinnamic aldehyde suppresses hypoxia-induced angiogenesis via inhibition of
      hypoxia-inducible factor-1alpha expression during tumor progression.
AB  - During tumor progression, hypoxia-inducible factor 1 (HIF-1) plays a critical
      role in tumor angiogenesis and tumor growth by regulating the transcription of
      several genes in response to a hypoxic environment and changes in growth factors.
      This study was designed to investigate the effects of cinnamic aldehyde (CA) on
      tumor growth and angiogenesis and the mechanisms underlying CA's anti-angiogenic
      activities. We found that CA administration inhibits tumor growth and blocks
      tumor angiogenesis in BALB/c mice. In addition, CA treatment decreased HIF-1alpha
      protein expression and vascular endothelial growth factor (VEGF) expression in
      mouse tumors and Renca cells exposed to hypoxia in vitro. Interestingly, CA
      treatment did not affect the stability of von Hippel-Lindau protein (pVHL)
      associated HIF-1alpha and CA attenuated the activation of mammalian target of
      rapamycin (mTOR) pathway. Collectively, these findings strongly indicate that the
      anti-angiogenic activity of CA is, at least in part, regulated by the mTOR
      pathway-mediated suppression of HIF-1alpha protein expression and these findings
      suggest that CA may be a potential drug for human cancer therapy. 

PMID- 26297911
TI  - A dipeptidyl peptidase-IV inhibitor improves hepatic steatosis and insulin
      resistance by AMPK-dependent and JNK-dependent inhibition of LECT2 expression.
AB  - Leukocyte cell-derived chemotaxin 2 (LECT2) is a recently discovered hepatokine
      that mediates obesity-related metabolic disturbances. Dipeptidyl peptidase-4 (DPP
      4) inhibitors are novel therapeutic agents for inflammatory disorders including
      nonalcoholic fatty liver disease (NAFLD). However, no research has examined the
      connections or functions of LECT2 and the novel DPP-4 inhibitor, gemigliptin, in
      NAFLD pathogenesis. High-fat diet (HFD)-fed C57BL/6 mice were used to investigate
      the effect of gemigliptin on hepatic steatosis and LECT2 expression. In the HepG2
      cell line, LECT2 and gemigliptin signaling were analyzed by Western blot. LECT2
      increased mammalian target of rapamycin (mTOR) phosphorylation, sterol regulatory
      element-binding protein (SREBP)-1 cleavage, lipid accumulation, and insulin
      resistance in HepG2 cells; these events were significantly decreased by treatment
      with a c-Jun N-terminal kinase (JNK) inhibitor. Gemigliptin increased AMP
      activated protein kinase (AMPK) phosphorylation and inhibited tumor necrosis
      factor (TNF) alpha-induced mTOR phosphorylation, SREBP-1 cleavage, lipid
      accumulation, and LECT2 expression in HepG2 cells; these events were attenuated
      by an AMPK inhibitor. Gemigliptin recovered TNFalpha-induced inhibition of
      insulin receptor substrate (IRS)-1 and Akt phosphorylation that was abolished in
      LECT2 knockdown cells or by AMPK inhibition. In preliminary in vivo experiments,
      gemigliptin induced AMPK phosphorylation and inhibited LECT2 expression in liver
      tissues from HFD-fed mice. Mice fed with HFD and gemigliptin showed improved
      hepatic steatosis and insulin resistance compared to HFD-fed mice. Gemigliptin
      might alleviate hepatic steatosis and insulin resistance by inhibiting LECT2
      expression by AMPK-dependent and JNK-dependent mechanisms, suggesting a direct
      protective effect against NAFLD progression. 

PMID- 26297912
TI  - Key Questions on the Role of Phenotypic Plasticity in Eco-Evolutionary Dynamics.
AB  - Ecology and evolution have long been recognized as reciprocally influencing each
      other, with recent research emphasizing how such interactions can occur even on
      very short (contemporary) time scales. Given that these interactions are mediated
      by organismal phenotypes, they can be variously shaped by genetic variation,
      phenotypic plasticity, or both. I here address 8 key questions relevant to the
      role of plasticity in eco-evolutionary dynamics. Focusing on empirical evidence,
      especially from natural populations, I offer the following conclusions. 1)
      Plasticity is--not surprisingly--sometimes adaptive, sometimes maladaptive, and
      sometimes neutral. 2) Plasticity has costs and limits but these constraints are
      highly variable, often weak, and hard to detect. 3) Variable environments favor
      the evolution of increased trait plasticity, which can then buffer
      fitness/performance (i.e., tolerance). 4) Plasticity sometimes aids colonization
      of new environments (Baldwin Effect) and responses to in situ environmental
      change. However, plastic responses are not always necessary or sufficient in
      these contexts. 5) Plasticity will sometimes promote and sometimes constrain
      genetic evolution. 6) Plasticity will sometimes help and sometimes hinder
      ecological speciation but, at present, empirical tests are limited. 7) Plasticity
      can show considerable evolutionary change in contemporary time, although the
      rates of this reaction norm evolution are highly variable among taxa and traits.
      8) Plasticity appears to have considerable influences on ecological dynamics at
      the community and ecosystem levels, although many more studies are needed. In
      summary, plasticity needs to be an integral part of any conceptual framework and
      empirical investigation of eco-evolutionary dynamics.

PMID- 26297913
TI  - What Do Primary and Secondary School Teachers Know About ADHD in Children?
      Findings From a Systematic Review and a Representative, Nationwide Sample of
      Danish Teachers.
AB  - OBJECTIVE: To identify what primary and secondary school teachers know about ADHD
      in children and, furthermore, to identify which factors predict their knowledge.
      METHOD: A 29-item questionnaire about ADHD was distributed to a random,
      nationwide, and representative sample of Danish primary and secondary school
      teachers. Data were analyzed descriptively and by hierarchical regression
      analysis. RESULTS: A total of 528 teachers were included. Most teachers
      identified the symptoms of ADHD (79%-96%) and effective classroom intervention
      strategies (75%-98%). However, knowledge about other characteristics, etiology,
      prognosis, and treatment was inconsistent, for example, only 56% and 17%
      correctly rejected diet as a cause and effective treatment for ADHD. Among the
      strongest predictors for correct knowledge was having been provided postgraduate
      education about ADHD. CONCLUSION: Teachers require knowledge about ADHD to
      successfully include and manage children with ADHD and, additionally, to ensure
      positive working environments for teachers and support constructive school-home
      working collaborations.

PMID- 26297914
TI  - Bordetella pertussis evolution in the (functional) genomics era.
AB  - The incidence of whooping cough caused by Bordetella pertussis in many developed
      countries has risen dramatically in recent years. This has been linked to the use
      of an acellular pertussis vaccine. In addition, it is thought that B. pertussis
      is adapting under acellular vaccine mediated immune selection pressure, towards
      vaccine escape. Genomics-based approaches have revolutionized the ability to
      resolve the fine structure of the global B. pertussis population and its
      evolution during the era of vaccination. Here, we discuss the current picture of
      B. pertussis evolution and diversity in the light of the current resurgence,
      highlight import questions raised by recent studies in this area and discuss the
      role that functional genomics can play in addressing current knowledge gaps. 

PMID- 26297915
TI  - Immunomodulation of host-protective immune response by regulating Foxp3
      expression and Treg function in Leishmania-infected BALB/c mice: critical role of
      IRF1.
AB  - Visceral leishmaniasis (VL), caused by a protozoan parasite Leishmania donovani,
      is still a threat to mankind due to treatment failure, drug resistance and
      coinfection with HIV. The limitations of first-line drugs have led to the
      development of new strategies to combat this dreaded disease. Recently, we have
      shown the immunomodulatory property of Ara-LAM, a TLR2 ligand, against
      leishmanial pathogenesis. In this study, we have extended our study to the effect
      of Ara-LAM on regulatory T cells in a murine model of VL. We observed that Ara
      LAM-treated infected BALB/c mice showed a strong host-protective Th1 immune
      response due to reduced IL-10 and TGF-beta production, along with marked decrease
      in CD4(+) CD25(+) Foxp3(+) GITR(+) CTLA4(+) regulatory T cell (Treg) generation
      and activation. The reduction in Foxp3 expression was due to effective modulation
      of TGF-beta-induced SMAD signaling in Treg cells by Ara-LAM. Moreover, we
      demonstrated that Ara-LAM-induced IRF1 expression in the Treg cells, which
      negatively regulated foxp3 gene transcription, resulting in the reduced
      immunosuppressive activity of Treg cells. Interestingly, irf1 gene knockdown
      completely abrogated the effect of Ara-LAM on Treg cells. Thus, these findings
      provide detailed mechanistic insight into Ara-LAM-mediated modulation of Treg
      cells, which might be helpful in combating VL. 

PMID- 26297916
TI  - Hypoxia impairs anti-viral activity of natural killer (NK) cells but has little
      effect on anti-fibrotic NK cell functions in hepatitis C virus infection.
AB  - BACKGROUND & AIMS: Natural killer (NK) cells have been shown to exert anti-viral
      as well as anti-fibrotic functions in hepatitis C virus (HCV) infection. Previous
      studies, however, analyzed NK cell functions exclusively under atmospheric oxygen
      conditions despite the fact that the liver microenvironment is hypoxic. Here, we
      analyzed the effects of low oxygen tension on anti-viral and anti-fibrotic NK
      cell activity. METHODS: Peripheral (n=34) and intrahepatic (n=15) NK cells from
      HCV(+) patients as well as circulating NK cells from healthy donors (n=20) were
      studied with respect to anti-viral and anti-fibrotic activity via co-culture
      experiments with HuH7 replicon cells and hepatic stellate cells, respectively.
      RESULTS: Anti-viral activity of resting NK cells from healthy controls was not
      affected by hypoxia. However, hypoxia significantly reduced the response of
      healthy NK cells to cytokine stimulation. In contrast to healthy controls, we
      observed resting and cytokine activated peripheral NK cells from HCV patients to
      display a significantly decreased anti-viral activity when cultured at 5% or 1%
      oxygen, suggesting HCV NK cells to be very sensitive to hypoxia. These findings
      could be confirmed when intrahepatic NK cells were tested. Finally, we show that
      anti-fibrotic NK cell activity was not affected by low oxygen tension.
      CONCLUSIONS: Our results show that anti-viral function of NK cells from HCV(+)
      patients is critically affected by a hypoxic microenvironment and, therefore,
      indicate that in order to obtain an accurate understanding of intrahepatic NK
      cell anti-HCV activity, the laboratory modelling should take into account the
      liver specific levels of oxygen.

PMID- 26297917
TI  - Contribution of beta-cell dysfunction and insulin resistance to cirrhosis
      associated diabetes: Role of severity of liver disease.
AB  - BACKGROUND & AIMS: This study evaluated the contribution of beta-cell dysfunction
      and insulin resistance to cirrhosis-associated diabetes. METHODS: One-hundred and
      sixty cirrhotic patients with normal fasting plasma glucose (FPG), three with
      impaired fasting glucose and seven with untreated diabetes mellitus (DM)
      underwent an extended oral glucose tolerance test (OGTT). The OGTT data were
      analyzed with a Minimal Model to estimate dynamic (derivative) control (DC) and
      static (proportional) control (PC) of beta-cell function, and with the Oral
      Glucose Insulin Sensitivity (OGIS)-2h index to estimate insulin sensitivity.
      RESULTS: Twenty-six patients (15.6%) had normal glucose tolerance (NGT), 60
      (35.8%) had impaired glucose tolerance (IGT), and 84 (48.6%) had DM. DC was
      significantly reduced in DM vs. NGT and IGT patients. PC was significantly
      impaired in DM and IGT vs. NGT patients and in DM vs. IGT subjects. The OGIS-2h
      index was significantly reduced to a similar extent in DM and IGT vs. NGT
      patients. Patients with Child-Pugh class B and C cirrhosis had reduced DC and PC,
      but not OGIS-2h values, as compared with subjects in class A. Moreover, Child
      Pugh class/score was an independent predictor of beta-cell function even after
      adjustment for glucose tolerance. CONCLUSIONS: Abnormalities of glucose tolerance
      occur frequently in cirrhosis even in patients with normal FPG, thereby
      supporting the importance of performing an OGTT. Transition from IGT to DM is
      driven primarily by beta-cell dysfunction. Insulin secretion worsens in parallel
      with the severity of liver disease, thus suggesting a detrimental effect of liver
      failure on pancreatic islets on its own.

PMID- 26297918
TI  - Primary biliary cirrhosis by another name is still PBC.

PMID- 26297919
TI  - Sedentary behaviour, physical activity, and NAFLD: Curse of the chair.

PMID- 26297920
TI  - Maintaining canine sperm function and osmolyte content with multistep freezing
      protocol and different cryoprotective agents.
AB  - Cryopreservation procedures cause osmotic stress to spermatozoa following
      cryoinjury and reduce their content of osmolytes. Conventional method for
      cryoprotectant loading and dilution on canine semen freezing which could be
      categorized in single step protocol, makes decreasing in sperm performance such
      as motility, morphology and viability. Therefore, the objective of the present
      study was to determine if a multistep protocol using glycerol or ethylene glycol
      can be used to overcome the osmotic sensitivity of canine spermatozoa, and to
      identify osmolytes that were involved in regulation of osmotic stress. A
      multistep protocol, comprising serial loading and dilution of cryoprotective
      agents by dividing the total volume of extender into 4 steps (14%, 19%, 27%, and
      40%) every 30s, was compared to a single step method. Frozen-thawed spermatozoa
      in the multistep group showed superior quality (P<0.05) compared with the single
      step process in progressive motility (23.3 +/- 1.3% vs. 12.5 +/- 1.6%), intact
      membranes (66.5 +/- 2.8% vs. 49.5 +/- 2.6%) and bent tail (29.2 +/- 3.2% vs. 46.2
      +/- 1.9%). Multistep also succeeded in minimizing loss of the osmolytes carnitine
      (20.6 +/- 2.0 nmol/U G6PDH vs. 10.8 +/- 2.1 nmol/U G6PDH) and glutamate (18.4 +/-
      1.6 nmol/U G6PDH vs. 14.4 +/- 0.8 nmol/U G6PDH) compared to the single step
      group. Moreover, glycerol with multistep was more advantageous for maintaining
      sperm quality than ethylene glycol. In conclusion, the multistep protocol with
      glycerol can be used to improve the morphology, motility and osmolytes content of
      frozen-thawed canine spermatozoa.

PMID- 26297921
TI  - An infection of human adenovirus 31 affects the differentiation of preadipocytes
      into fat cells, its metabolic profile and fat accumulation.
AB  - The primary issue undertaken in this study was to test the hypothesis that
      preadipocytes would have intrinsically elevated propensity to differentiate into
      mature adipocytes due to HAdV31 infection. To prove that, the metabolic and
      molecular mechanisms responsible for HAdV31-induced adipogenesis were examined.
      3T3L1 cells (mouse embryonic fibroblast, adipose like cell line) were used as a
      surrogate model to analyze an increased proliferation, differentiation, and
      maturation of preadipocytes infected with human adenovirus. An expression of
      E4orf1, C/EBP-beta, PPAR-gamma, GAPDH, aP2, LEP, and fatty acid synthase genes,
      intracellular lipid accumulation as well as cytokine release from the fat cells
      were assessed. Data showed that HAdV31 increased an expression of C/EBP-beta and
      PPAR-gamma genes leading to an enhanced differentiation of preadipocytes into fat
      cells. Besides, overexpression of GAPDH and fatty acid synthase, and decreased
      expression of leptin caused an increased accumulation of intracellular lipids.
      Secretion of TNF-alpha and IL-6 from HAdV31-infected cells was strongly
      decreased, leading to unlimited virus replication. The results obtained from this
      study provided the evidences that HAdV31, likewise previously documented HAdV36,
      is a subsequent human adenovirus affecting the differentiation and lipid
      accumulation of 3T3L1 cells.

PMID- 26297923
TI  - 2014 Ogura lecture: When more than the patient is ill: Healing sick systems.

PMID- 26297922
TI  - Crispld2 is required for neural crest cell migration and cell viability during
      zebrafish craniofacial development.
AB  - The CAP superfamily member, CRISPLD2, has previously been shown to be associated
      with nonsyndromic cleft lip and palate (NSCLP) in human populations and to be
      essential for normal craniofacial development in the zebrafish. Additionally, in
      rodent models, CRISPLD2 has been shown to play a role in normal lung and kidney
      development. However, the specific role of CRISPLD2 during these developmental
      processes has yet to be determined. In this study, it was demonstrated that
      Crispld2 protein localizes to the orofacial region of the zebrafish embryo and
      knockdown of crispld2 resulted in abnormal migration of neural crest cells (NCCs)
      during both early and late time points. An increase in cell death after crispld2
      knockdown as well as an increase in apoptotic marker genes was also shown. This
      data suggests that Crispld2 modulates the migration, differentiation, and/or
      survival of NCCs during early craniofacial development. These results indicate an
      important role for Crispld2 in NCC migration during craniofacial development and
      suggests involvement of Crispld2 in cell viability during formation of the
      orofacies.

PMID- 26297924
TI  - Characterizing the effects of bisphenol A on sediment-dwelling benthic organisms.
AB  - Bisphenol A (BPA) is a high production volume chemical intermediate used
      primarily in the production of polycarbonate plastics and epoxy resins. It
      primarily enters surface water and sediment via effluent discharges during its
      manufacture and use. The physical properties of BPA suggest that sediment is a
      potential sink and may result in exposure to benthic organisms. Currently there
      are no studies measuring the chronic toxicity of BPA to benthic organisms via
      direct sediment exposure. The present study examined the chronic toxicity of BPA
      to 3 commonly used test organisms that are generally representative of
      invertebrates occupying the base of the benthic food web and for which
      standardized testing protocols are available: the oligochaete Lumbriculus
      variegatus (mean numbers and biomass), the midge Chironomus riparius (emergence
      and development rate), and the estuarine amphipod Leptocheirus plumulosus
      (survival, growth, and reproduction). No-observed-effect concentrations (NOECs)
      for the 3 species ranged from 12 mg/kg to 54 mg/kg dry weight. All NOEC values
      were higher than all measured concentrations of BPA in freshwater and marine
      sediments reported in reliable, fully reported studies from North America and
      Europe from the 1990s to the present. For the first time, there are studies with
      BPA measuring the chronic toxicity to 3 taxa of sediment dwelling invertebrates,
      which are suitable to support region-specific risk assessments.

PMID- 26297925
TI  - The association between economic development, lifestyle differentiation, and C
      reactive protein concentration within rural communities in Hainan Island, China.
AB  - OBJECTIVE: Earlier fieldwork in rural areas of Hainan Island, China, demonstrated
      that during the course of economic development increasing differences had emerged
      in lifestyles within communities. It is possible that these variations might have
      stratified residents into subpopulations with different health attributes. This
      study examined the association between C-reactive protein (CRP) concentration, a
      biomarker of future cardiovascular events, and personal lifestyle parameters and
      the degree of community-level economic development among rural communities.
      METHODS: A cross-sectional field survey was undertaken in 19 rural communities in
      Hainan. Convenience sampling was used to recruit 1,744 participants. Dried blood
      spot samples were collected to measure high-sensitivity CRP concentration. Sex
      stratified multilevel regression analyses were conducted to identify factors
      associated with CRP concentration among the participants. RESULTS: While CRP
      concentration was negatively associated with being married and (more) education
      among men, for women CRP concentration was associated with the frequency of
      poultry consumption (P = 0.014) and the experience of migratory work in the
      previous year (P = 0.009). In addition, for females, living in communities with a
      greater degree of inequality, as indexed by the Gini coefficient, was also
      associated with increased CRP concentration (P = 0.003). CONCLUSION: Given that
      CRP concentration is a marker of future CVD risk, this study suggests that within
      these previously homogenous rural communities, economic development might have
      stratified people into population subgroups with a different CVD risk.

PMID- 26297926
TI  - Membrane-induced structure of novel human tachykinin hemokinin-1 (hHK1).
AB  - PPT-C encoded hemokinin-1(hHK-1) of Homo sapiens (TGKASQFFGLM) is a structurally
      distinct neuropeptide among the tachykinin family that participate in the NK-1
      receptor downstream signaling processes. Subsequently, signal transduction leads
      to execution of various effector functions which includes aging, immunological,
      and central nervous system (CNS) regulatory actions. However the conformational
      pattern of ligand receptor binding is unclear. The three-dimensional structure of
      the hemokinin-1 in aqueous and micellar environment has been studied by one and
      two-dimensional proton nuclear magnetic resonance (2D 1H-NMR spectroscopy) and
      distance geometry calculations. Data shows that hemokinin-1 was unstructured in
      aqueous environment; anionic detergent SDS induces alpha-helix formation. Proton
      NMR assignments have been carried out with the aid of correlation spectroscopy
      (gradient-COSY and TOCSY) and nuclear Overhauser effect spectroscopy (NOESY and
      ROESY) experiments. The inter proton distances and dihedral angle constraints
      obtained from the NMR data have been used in torsion angle dynamics algorithm for
      NMR applications (CYANA) to generate a family of structures, which have been
      refined using restrained energy minimization and dynamics. Helical conformation
      is observed from residue K3-M11. The conformational range of the peptide revealed
      by NMR studies has been analyzed in terms of characteristic secondary features.
      Observed conformational features have been compared to that of Substance P potent
      NK1 agonist. Thus the report provides a structural insight to study hHK-1-NK1
      interaction that is essential for hHK1 based signaling events.

PMID- 26297927
TI  - Dynamics and thermodynamic properties of CXCL7 chemokine.
AB  - Chemokines form a family of signaling proteins mainly responsible for directing
      the traffic of leukocytes, where their biological activity can be modulated by
      their oligomerization state. We characterize the dynamics and thermodynamic
      stability of monomer and homodimer structures of CXCL7, one of the most abundant
      platelet chemokines, using experimental methods that include circular dichroism
      (CD) and nuclear magnetic resonance (NMR) spectroscopy, and computational methods
      that include the anisotropic network model (ANM), molecular dynamics (MD)
      simulations and the distance constraint model (DCM). A consistent picture emerges
      for the effects of dimerization and Cys5-Cys31 and Cys7-Cys47 disulfide bonds
      formation. The presence of disulfide bonds is not critical for maintaining
      structural stability in the monomer or dimer, but the monomer is destabilized
      more than the dimer upon removal of disulfide bonds. Disulfide bonds play a key
      role in shaping the characteristics of native state dynamics. The combined
      analysis shows that upon dimerization flexibly correlated motions are induced
      between the 30s and 50s loop within each monomer and across the dimer interface.
      Interestingly, the greatest gain in flexibility upon dimerization occurs when
      both disulfide bonds are present, and the homodimer is least stable relative to
      its two monomers. These results suggest that the highly conserved disulfide bonds
      in chemokines facilitate a structural mechanism that is tuned to optimally
      distinguish functional characteristics between monomer and dimer.

PMID- 26297928
TI  - Antihypertensive and cardioprotective effects of the dipeptide isoleucine
      tryptophan and whey protein hydrolysate.
AB  - AIMS: Angiotensin-converting enzyme inhibitors are treatment of choice in
      hypertensive patients. Clinically used inhibitors exhibit a structural similarity
      to naturally occurring peptides. This study evaluated antihypertensive and
      cardioprotective effects of ACE-inhibiting peptides derived from food proteins in
      spontaneously hypertensive rats. METHODS AND RESULTS: Isoleucine-tryptophan (in
      vitro IC50 for ACE = 0.7 MUm), a whey protein hydrolysate containing an augmented
      fraction of isoleucine-tryptophan, or captopril was given to spontaneously
      hypertensive rats (n = 60) over 14 weeks. Two further groups, receiving either no
      supplement (Placebo) or intact whey protein, served as controls. Systolic blood
      pressure age-dependently increased in the Placebo group, whereas the blood
      pressure rise was effectively blunted by isoleucine-tryptophan, whey protein
      hydrolysate and captopril (-42 +/- 3, -38 +/- 5, -55 +/- 4 mm Hg vs. Placebo). At
      study end, myocardial mass was lower in isoleucine-tryptophan and captopril
      groups but only partially in the hydrolysate group. Coronary flow reserve (1 MUm
      adenosine) was improved in isoleucine-tryptophan and captopril groups. Plasma ACE
      activity was significantly decreased in isoleucine-tryptophan, hydrolysate and
      captopril groups, but in aortic tissue only after isoleucine-tryptophan or
      captopril treatment. This was associated with lowered expression and activity of
      matrix metalloproteinase-2. Following isoleucine-tryptophan and captopril
      treatments, gene expression of renin was significantly increased indicating an
      active feedback within renin-angiotensin system. CONCLUSION: Whey protein
      hydrolysate and isoleucine-tryptophan powerfully inhibit plasma ACE resulting in
      antihypertensive effects. Moreover, isoleucine-tryptophan blunts tissue ACE
      activity, reduces matrix metalloproteinase-2 activity and improves coronary flow
      reserve. Thus, whey protein hydrolysate and particularly isoleucine-tryptophan
      may serve as innovative food additives with the goal of attenuating hypertension.

PMID- 26297929
TI  - On the effect of hydrostatic pressure on the conformational stability of globular
      proteins.
AB  - The model developed for cold denaturation (Graziano, PCCP 2010, 12, 14245-14252)
      is extended to rationalize the dependence of protein conformational stability
      upon hydrostatic pressure, at room temperature. A pressure- volume work is
      associated with the process of cavity creation for the need to enlarge the liquid
      volume against hydrostatic pressure. This contribution destabilizes the native
      state that has a molecular volume slightly larger than the denatured state due to
      voids existing in the protein core. Therefore, there is a hydrostatic pressure
      value at which the pressure-volume contribution plus the conformational entropy
      loss of the polypeptide chain are able to overwhelm the stabilizing gain in
      translational entropy of water molecules, due to the decrease in water accessible
      surface area upon folding, causing denaturation.

PMID- 26297931
TI  - Otolaryngological manifestations of Measles (Rubeola): A case report and brief
      review.
AB  - Measles is an acute viral respiratory illness caused by a virus of the
      Paramyxoviridae family. Despite being eliminated from the United States, small
      outbreaks across the country continue to occur. The United States experienced a
      record number of cases in 2014, with 668 cases seen across the country, a record
      since its elimination in 2000. Here, we present a case of an acute presentation
      of measles illness and discuss the otolaryngologic manifestation of the disease.
      Laryngoscope, 126:1481-1483, 2016.

PMID- 26297930
TI  - Squamous cell carcinoma of the nasal cavity: A population-based analysis.
AB  - OBJECTIVES/HYPOTHESIS: Squamous cell carcinoma of the nasal cavity (NCSCC) is an
      infrequent malignancy that has been historically difficult to characterize. This
      study provides new insight into NCSCC utilizing a population-based database. We
      analyze the propensity for cervical and distant metastasis from NCSCC, as well as
      survival outcomes. STUDY DESIGN: Retrospective database analysis. METHODS: The
      Surveillance, Epidemiology, and End Results (SEER) database (2004-2012) was
      queried for NCSCC cases. Data were analyzed with respect to various demographic
      and clinicopathologic factors. The results were further examined for regional and
      distant metastasis. Survival was analyzed using the Kaplan-Meier model. RESULTS:
      A total of 1,180 cases of NCSCC were identified in the SEER database between 2004
      and 2012. The mean age at diagnosis was 65.8 years. American Joint Committee on
      Cancer stage was known in 1,050 cases, of which 53.4% were stage I, 13.3% were
      stage II, 10.2% were stage III, and 23.0% were stage IV. By tumor (T) stage
      classification, T1 was the most common (56.6%), followed by T4 (19.3%). Most
      cases had no nodal (N) involvement at diagnosis (90.8%). Cervical nodal
      involvement was present in 9.1% of cases, while distant metastasis was seen in
      1.9%. Five-year disease-specific survival was 69.5% overall, 39.6% in cases with
      neck involvement and 0.0% for metastatic cases. CONCLUSIONS: This study
      represents the only known population-based investigation of NCSCC. Metastasis to
      cervical nodes or distant sites, especially with T1 tumors, is rare. However, any
      cervical involvement or distant metastasis discovered on presentation is a poor
      prognostic indicator. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:560-565, 2016.

PMID- 26297932
TI  - Nuclear alpha Spectrin Differentially Affects Monoubiquitinated Versus Non
      Ubiquitinated FANCD2 Function After DNA Interstrand Cross-Link Damage.
AB  - Nonerythroid alpha spectrin (alphaIISp) and the Fanconi anemia (FA) protein,
      FANCD2, play critical roles in DNA interstrand cross-link (ICL) repair during S
      phase. Both are needed for recruitment of repair proteins, such as XPF, to sites
      of damage and repair of ICLs. However, the relationship between them in ICL
      repair and whether alphaIISp is involved in FANCD2's function in repair is
      unclear. The present studies show that, after ICL formation, FANCD2 disassociates
      from alphaIISp and localizes, before alphaIISp, at sites of damage in nuclear
      foci. alphaIISp and FANCD2 foci do not co-localize, in contrast to our previous
      finding that alphaIISp and the ICL repair protein, XPF, co-localize and follow a
      similar time course for formation. Knock-down of alphaIISp has no effect on
      monoubiquitination of FANCD2 (FANCD2-Ub) or its localization to chromatin or
      foci, though it leads to decreased ICL repair. Studies using cells from FA
      patients, defective in ICL repair and alphaIISp, have elucidated an important
      role for alphaIISp in the function of non-Ub FANCD2. In FA complementation group
      A (FA-A) cells, in which FANCD2 is not monoubiquitinated and does not form damage
      induced foci, we demonstrate that restoration of alphaIISp levels to normal, by
      knocking down the protease MU-calpain, leads to formation of non-Ub FANCD2 foci
      after ICL damage. Since restoration of alphaIISp levels in FA-A cells restores
      DNA repair and cell survival, we propose that alphaIISp is critical for
      recruitment of non-Ub FANCD2 to sites of damage, which has an important role in
      the repair response and ICL repair.

PMID- 26297933
TI  - A clinical trial of Integra Template for diabetic foot ulcer treatment.
AB  - Individuals with diabetes mellitus are at an increased risk of developing a
      diabetic foot ulcer (DFU). This study evaluated the safety and efficacy of
      Integra Dermal Regeneration Template (IDRT) for the treatment of nonhealing DFUs.
      The Foot Ulcer New Dermal Replacement Study was a multicenter, randomized,
      controlled, parallel group clinical trial conducted under an Investigational
      Device Exemption. Thirty-two sites enrolled and randomized 307 subjects with at
      least one DFU. Consented patients were entered into the 14-day run-in phase where
      they were treated with the standard of care (0.9% sodium chloride gel) plus a
      secondary dressing and an offloading/protective device. Patients with less than
      30% reepithelialization of the study ulcer after the run-in phase were randomized
      into the treatment phase. The subjects were randomized to the control treatment
      group (0.9% sodium chloride gel; n = 153) or the active treatment group (IDRT, n
      = 154). The treatment phase was 16 weeks or until confirmation of complete wound
      closure (100% reepithelialization of the wound surface), whichever occurred
      first. Following the treatment phase, all subjects were followed for 12 weeks.
      Complete DFU closure during the treatment phase was significantly greater with
      IDRT treatment (51%) than control treatment (32%; p = 0.001) at sixteen weeks.
      The median time to complete DFU closure was 43 days for IDRT subjects and 78 days
      for control subjects in wounds that healed. The rate of wound size reduction was
      7.2% per week for IDRT subjects vs. 4.8% per week for control subjects (p =
      0.012). For the treatment of chronic DFUs, IDRT treatment decreased the time to
      complete wound closure, increased the rate of wound closure, improved components
      of quality of life and had less adverse events compared with the standard of care
      treatment. IDRT could greatly enhance the treatment of nonhealing DFUs. 

PMID- 26297934
TI  - Medial humeral epicondylitis in clinically affected cats.
AB  - OBJECTIVE: To describe the clinical signs and histologic changes in cats
      clinically affected with medial humeral epicondylitis (MHE) and evaluate long
      term outcome after either conservative or surgical treatment. STUDY DESIGN:
      Prospective cohort study. ANIMALS: Client-owned cats (n = 17) with MHE. METHODS:
      Cats diagnosed with MHE, based on clinical signs, radiographs and computed
      tomography (CT), were prospectively recruited. Cats were treated conservatively
      for an initial 4 weeks, followed by either surgery or continued conservative
      treatment. Followup examinations were performed at 6 and 12 weeks and at 6-49
      months. RESULTS: Cats had a mean age of 10.3 years and presented for chronic
      lameness. Examination revealed pain on palpation caudodistal to the medial
      epicondyle and by exerting antebrachial supination/pronation with elbow and
      carpal flexion. Lameness was restricted to 1 limb although CT revealed bilateral
      disease in 11/17 cats. Free mineralized joint bodies were identified in 9/17
      cats. Nine cats were treated surgically and 8 cats were treated conservatively.
      Intraoperative findings included new bone formation at the origin of the humeral
      head of the flexor carpi ulnaris muscle with displacement and adhesions of the
      ulnar nerve. Microscopic examination revealed neurogenic myopathy in 4/9 cats
      treated surgically. Seven of 9 cats treated surgically were free from lameness by
      12 weeks. Seven of 8 cats treated conservatively were chronically lame throughout
      the study. CONCLUSIONS: Cats with forelimb lameness should be evaluated for MHE.
      This condition is associated with free joint bodies and neurogenic myopathy.
      Surgical treatment is associated with excellent outcome in the majority of cats.

PMID- 26297935
TI  - Does septoplasty performed at the same time as oropharyngeal surgery increase
      complication rates?
AB  - OBJECTIVES/HYPOTHESIS: To determine whether septoplasty when combined with
      ambulatory oropharyngeal surgery increases postoperative complications. STUDY
      DESIGN: Cross-sectional analysis of multistate ambulatory surgery and hospital
      databases. METHODS: Ambulatory adult septoplasty and oropharyngeal surgical
      procedures (tonsillectomy and uvulopalatoplasty [UPPP]) were extracted from the
      state ambulatory surgery databases for New York, Florida, Iowa, and California
      for 2010-2011. Cases with concurrent sinus surgery were excluded. Cases were
      linked to the state emergency department databases and the state inpatient
      databases to identify revisits within 14 days. The rates of unplanned revisits
      and postoperative bleeding were determined and compared among groups undergoing
      solely oropharyngeal surgery versus groups undergoing oropharyngeal surgery
      combined with septoplasty. RESULTS: Among 26,280 tonsillectomies alone versus
      1,002 tonsillectomies + septoplasty, rates for unplanned revisits and hemorrhage
      were 13.2% and 12.8% (P = .66) and 4.9% and 7.0% (P = .003), respectively. Among
      2,598 UPPPs alone versus 1,343 UPPPs + septoplasty, rates for revisits and
      hemorrhage were 11.4% versus 10.1% (P = .242) and 3.5% versus 3.8% (P = 0.683),
      respectively. Among 389 UPPP/tonsillectomies versus 164 UPPP/tonsillectomies +
      septoplasty, rates for revisits and hemorrhage were 11.8% versus 8.5% (P = .256)
      and 3.9% versus 6.1% (P = .247), respectively. Among all cases and groups, there
      were mortalities only in the UPPP alone group. CONCLUSIONS: The addition of
      septoplasty to oropharyngeal ambulatory surgical procedures does not
      significantly increase the rate of unplanned revisits or postoperative hemorrhage
      except in the case of septoplasty added to tonsillectomy, with a small percentage
      increase in hemorrhage rate. Combining septoplasty with ambulatory oropharyngeal
      surgery is clinically reasonable in adults. LEVEL OF EVIDENCE: 2b.

PMID- 26297936
TI  - Chronic pain in Noonan Syndrome: A previously unreported but common symptom.
AB  - Noonan syndrome (NS) is a multiple malformation syndrome characterized by
      pulmonic stenosis, cardiomyopathy, short stature, lymphatic dysplasia,
      craniofacial anomalies, cryptorchidism, clotting disorders, and learning
      disabilities. Eight genes in the RAS/MAPK signaling pathway are implicated in NS.
      Chronic pain is an uncommon feature. To investigate the prevalence of pain in NS,
      we distributed a two-part questionnaire about pain among NS individuals at the
      Third International Meeting on Genetic Syndromes of the Ras/MAPK Pathway. The
      first part of the questionnaire queried demographic information among all NS
      participants. The second part was completed by individuals with chronic pain.
      Questions included musculoskeletal problems and clinical features of pain. Forty
      five questionnaires were analyzed; 53% of subjects were female. Mean age was 17
      (2-48) years; 47% had a PTPN11 mutation. Sixty-two percent (28/45) of individuals
      with NS experienced chronic pain. There was a significant relationship between
      prevalence of pain and residing in a cold climate (P = 0.004). Pain occurred
      commonly in extremities/joints and head/trunk, but more commonly in
      extremities/joints (P = 0.066). Subjects with hypermobile joints were more likely
      to have pain (P = 0.052). Human growth hormone treatment was not statistically
      significant among subjects without chronic pain (P = 0.607). We conclude that
      pain is a frequent and under-recognized clinical feature of NS. Chronic pain may
      be associated with joint hypermobility and aggravated by colder climate. Our
      study is a preliminary investigation that should raise awareness about pain as a
      common symptom in children and adults with NS.

PMID- 26297937
TI  - Patterns of Alcohol Consumption and Risk of Frailty in Community-dwelling Older
      Adults.
AB  - BACKGROUND: Consumption of moderate-to-heavy amounts of alcohol has been
      associated with lower risk of cardiovascular disease and diabetes. Although both
      diseases are main causes of the frailty syndrome, no previous study has assessed
      the association between alcohol-drinking patterns and risk of frailty in older
      adults. METHODS: A prospective cohort study of 2,086 community-dwelling
      individuals aged 60 and older, recruited in 2008-2010, and followed through 2012,
      was carried out. Drinking patterns were self-reported at baseline. Moderate
      drinking was defined as alcohol intake less than 40 g/day for men and less than
      24 g/day for women. A Mediterranean drinking pattern was defined as moderate
      alcohol intake, with wine preference (>=80% of alcohol proceeds from wine) and
      drinking only with meals. Study participants were followed through 2012 to
      ascertain incident frailty, defined as >=2 of the following 4 Fried criteria:
      exhaustion, muscle weakness, low physical activity, and slow walking speed.
      Analyses were performed with logistic regression and adjusted for the main
      confounders. RESULTS: After a mean follow-up of 3.3 (SD = 0.6) years, 292
      participants with incident frailty were identified. Compared with nondrinkers,
      the odds ratio and its 95% confidence interval of frailty was 0.90 (0.65-1.25)
      for moderate drinkers. The corresponding results were 0.74 (0.48-1.16) for wine
      versus other beverage preference and 0.53 (0.31-0.92) for drinking only with
      meals versus only outside meals. Finally, compared with nondrinkers, the odds
      ratio (95% confidence interval) of frailty was 0.68 (0.47-0.99) for those
      adhering to the Mediterranean drinking pattern. CONCLUSIONS: Certain drinking
      patterns, in particular drinking only with meals and the Mediterranean drinking
      pattern, are associated with a lower risk of frailty in older adults.

PMID- 26297938
TI  - Regulatory T Cells, Frailty, and Immune Activation in Men Who Have Sex With Men
      in the Multicenter AIDS Cohort Study.
AB  - BACKGROUND: Both HIV infection and frailty have been associated with chronic
      immune activation. One possible explanation for this chronic immune activation
      could be low levels of CD4(+) T regulatory cells (Tregs), which suppress immune
      responses. METHODS: HIV-uninfected (HIV-) and HIV-infected (HIV+) men in the
      Multicenter AIDS Cohort Study (MACS) were classified as frail (or nonfrail) if
      they expressed (or did not express) the Fried frailty phenotype at two
      consecutive study visits. Percentages and absolute numbers of total Tregs, and
      percentages of different subsets of Tregs and of activated T cells were measured
      by flow cytometry. The function of Tregs was measured by suppression of T-cell
      proliferation. RESULTS: Percentages of Tregs were higher, rather than lower, in
      frail men than in nonfrail men, and this difference was significant for HIV- men.
      Percentages of subsets of Tregs did not differ significantly by frailty status.
      Among HIV+ men, the suppressive function of Tregs was similar between frail and
      nonfrail men. Percentages of Tregs and activated T cells were negatively
      correlated in nonfrail men (HIV- and HIV+) and in frail HIV- men, but this
      correlation was strongly positive in frail HIV+ men. CONCLUSION: These data
      suggest that: (a) Tregs were not deficient in frail men; and (b) the
      immunological pathophysiology of frailty may differ by HIV status.

PMID- 26297939
TI  - Mitochondrial Aging and Physical Decline: Insights From Three Generations of
      Women.
AB  - Decline in mitochondrial DNA (mtDNA) copy number, function, and accumulation of
      mutations and deletions have been proposed to contribute to age-related physical
      decline, based on cross sectional studies in genetically unrelated individuals.
      There is wide variability of mtDNA and functional measurements in many population
      studies and therefore we assessed mitochondrial function and physical function in
      18 families of grandmothers, mothers, and daughters who share the same maternally
      inherited mtDNA sequence. A significant age-related decline in mtDNA copy number,
      mitochondrial protein expression, citrate synthase activity, cytochrome c oxidase
      content, and VO2 peak were observed. Also, a lower abundance of SIRT3,
      accompanied by an increase in acetylated skeletal muscle proteins, was observed
      in grandmothers. Muscle tissue-based full sequencing of mtDNA showed greater than
      5% change in minor allele frequency over a lifetime in two locations, position
      189 and 408 in the noncoding D-loop region but no changes were noted in blood
      cells mtDNA. The decline in oxidative capacity and muscle function with age in
      three generations of women who share the same mtDNA sequence are associated with
      a decline in muscle mtDNA copy number and reduced protein deacetylase activity of
      SIRT3. 

PMID- 26297940
TI  - Yoga Is as Good as Stretching-Strengthening Exercises in Improving Functional
      Fitness Outcomes: Results From a Randomized Controlled Trial.
AB  - BACKGROUND: Despite yoga's popularity, few clinical trials have employed rigorous
      methodology to systematically explore its functional benefits compared with more
      established forms of exercise. The objective of this study was to compare the
      functional benefits of yoga with the conventional stretching-strengthening
      exercises recommended for adults. METHODS: Sedentary healthy adults (N = 118; M
      age = 62.0) participated in an 8-week (three times a week for 1 hour) randomized
      controlled trial, which consisted of a Hatha yoga group (n = 61) and a stretching
      strengthening exercise group (n = 57). Standardized functional fitness tests
      assessing balance, strength, flexibility, and mobility were administered at
      baseline and postintervention. RESULTS: A repeated measures multivariate analysis
      of variance showed a significant time effect for measures of balance [F(3,18) =
      4.88, p < .01, partial eta(2) = .45], strength [F(2,19) = 15.37, p < .001,
      partial eta(2) = .62], flexibility [F(4,17) = 8.86, p < .001, partial eta(2) =
      .68], and mobility [F(2,19) = 8.54, p < .002, partial eta(2) = .47]. Both groups
      showed significant improvements on measures of balance (left-right leg and four
      square step); strength (chair stands and arm curls); flexibility (back scratch
      and sit-and-reach); and mobility (gait speed and 8-feet up and go), with partial
      eta(2) ranging from .05 to .47. CONCLUSIONS: These data suggest that regular yoga
      practice is just as effective as stretching-strengthening exercises in improving
      functional fitness. To our knowledge, this is the first study to examine
      functional benefits of yoga in comparison with stretching-strengthening exercises
      in sedentary, healthy, community-dwelling older adults. These findings have
      clinical implications as yoga is a more amenable form of exercise than
      strengthening exercises as it requires minimal equipment and can be adapted for
      individuals with lower levels of functioning or disabilities.

PMID- 26297941
TI  - Measures of Healthspan as Indices of Aging in Mice-A Recommendation.
AB  - Over the past decade, a large number of discoveries have shown that interventions
      (genetic, pharmacological, and nutritional) increase the lifespan of
      invertebrates and laboratory rodents. Therefore, the possibility of developing
      antiaging interventions for humans has gone from a dream to a reality. However,
      it has also become apparent that we need more information than just lifespan to
      evaluate the translational potential of any proposed antiaging intervention to
      humans. Information is needed on how an intervention alters the "healthspan" of
      an animal, that is, how the physiological functions that change with age are
      altered. In this report, we describe the utility and the limitations of assays in
      mice currently available for measuring a wide range of physiological functions
      that potentially impact quality of life. We encourage investigators and reviewers
      alike to expect at minimum an overall assessment of health in several domains
      across several ages before an intervention is labeled as "increasing healthspan."
      In addition, it is important that investigators indicate any tests in which the
      treated group did worse or did not differ statistically from controls because
      overall health is a complex phenotype, and no intervention discovered to date
      improves every aspect of health. Finally, we strongly recommend that functional
      measurements be performed in both males and females so that sex differences in
      the rate of functional decline in different domains are taken into consideration.

PMID- 26297943
TI  - Neurodevelopmental outcome at 2 years in twin-twin transfusion syndrome survivors
      randomized for the Solomon trial.
AB  - BACKGROUND: The preferred treatment for twin-twin transfusion syndrome is
      fetoscopic laser coagulation of inter-twin vascular anastomoses on the
      monochorionic placenta. Severe postoperative complications can occur when inter
      twin vascular anastomoses remain patent including twin-anemia polycythemia
      sequence or recurrent twin-twin transfusion syndrome. To minimize the occurrence
      of residual anastomoses, a modified laser surgery technique, the Solomon
      technique, was developed in which the entire vascular equator is coagulated. In
      the Solomon randomized controlled trial (NTR1245), the Solomon technique was
      associated with a significant reduction in twin-anemia polycythemia sequence and
      recurrence of twin-twin transfusion syndrome when compared with the standard
      laser surgery technique. Although a significant improvement in perinatal outcome
      was shown after the Solomon technique, the clinical importance should also be
      ascertained with long-term follow-up evaluation of the surviving children.
      OBJECTIVE: The purpose of this study was to compare the long-term
      neurodevelopmental outcome in surviving children with twin-twin transfusion
      syndrome who were included in the Solomon randomized trial and treated with
      either the Solomon technique or standard laser surgery technique. STUDY DESIGN:
      Routine standardized follow-up evaluation in survivors, at least 2 years after
      the estimated date of delivery, was performed at 2 of the 5 centers that
      participated in the Solomon trial: Buzzi Hospital Milan (Italy) and Leiden
      University Medical Center (The Netherlands). The primary outcome of this follow
      up study was survival without long-term neurodevelopmental impairment at age 2
      years. Neurodevelopmental impairment was defined as cerebral palsy, cognitive
      and/or motor development score of <85, bilateral blindness, or deafness.
      Cognitive and motor development was evaluated with the use of Bayley-III. All
      analyses per fetus, neonate, or child were conducted with the generalized
      estimated equation module to account for the effect that observations between co
      twins are not independent. RESULTS: The primary outcome (survival without
      neurodevelopmental impairment) was detected in 95 of 141 cases (67%) in the
      Solomon group and in 99 of 146 cases (68%) in the standard group (P = .92).
      Neurodevelopmental impairment in long-term survivors who were included for follow
      up evaluation was detected in 12 of 107 cases (11%) in the Solomon and in 10 of
      109 cases (9%) in the standard group (P = .61). Neurodevelopmental impairment was
      due to cerebral palsy in 1 case (1%; spastic unilateral) in the Solomon group and
      in 2 cases (2%; spastic unilateral and spastic bilateral) in the standard group
      (P = .58). Cognitive development <85 cases was detected in 2 of 105 children (2%)
      in the Solomon group and in 6 of 106 children (6%) in the standard group (P =
      .23). Motor development <85 occurred in 8 of 103 children (8%) in the Solomon
      group and 3 of 104 children (3%) in the standard group (P = .23). CONCLUSION: We
      found no difference in survival without neurodevelopmental impairment between the
      Solomon and standard laser techniques. In view of the reduction of short-term
      complications and the absence of increased adverse long-term effects, these data
      support the use of the Solomon technique in the treatment of twin-twin
      transfusion syndrome.

PMID- 26297944
TI  - Antitumor dendritic cell-based vaccines: lessons from 20 years of clinical trials
      and future perspectives.
AB  - Dendritic cells (DCs) are versatile elements of the immune system and are best
      known for their unparalleled ability to initiate and modulate adaptive immune
      responses. During the past few decades, DCs have been the subject of numerous
      studies seeking new immunotherapeutic strategies against cancer. Despite the
      initial enthusiasm, disappointing results from early studies raised some doubts
      regarding the true clinical value of these approaches. However, our expanding
      knowledge of DC immunobiology and the definition of the optimal characteristics
      for antitumor immune responses have allowed a more rational development of DC
      based immunotherapies in recent years. Here, after a brief overview of DC
      immunobiology, we sought to systematize the knowledge provided by 20 years of
      clinical trials, with a special emphasis on the diversity of approaches used to
      manipulate DCs and their consequent impact on vaccine effectiveness. We also
      address how new therapeutic concepts, namely the combination of DC vaccines with
      other anticancer therapies, are being implemented and are leveraging clinical
      outcomes. Finally, optimization strategies, new insights, and future perspectives
      on the field are also highlighted. 

PMID- 26297942
TI  - Gait Speed Predicts Incident Disability: A Pooled Analysis.
AB  - BACKGROUND: Functional independence with aging is an important goal for
      individuals and society. Simple prognostic indicators can inform health promotion
      and care planning, but evidence is limited by heterogeneity in measures of
      function. METHODS: We performed a pooled analysis of data from seven studies of
      27,220 community-dwelling older adults aged 65 or older with baseline gait speed,
      followed for disability and mortality. Outcomes were incident inability or
      dependence on another person in bathing or dressing; and difficulty walking 1/4 -
      1/2 mile or climbing 10 steps within 3 years. RESULTS: Participants with faster
      baseline gait had lower rates of incident disability. In subgroups (defined by
      0.2 m/s-wide intervals from <0.4 to >= 1.4 m/s) with increasingly greater gait
      speed, 3-year rates of bathing or dressing dependence trended from 10% to 1% in
      men, and from 15% to 1% in women, while mobility difficulty trended from 47% to
      4% in men and 40% to 6% in women. The age-adjusted relative risk ratio per 0.1
      m/s greater speed for bathing or dressing dependence in men was 0.68 (0.57-0.81)
      and in women: 0.74 (0.66-0.82); for mobility difficulty, men: 0.75 (0.68-0.82),
      women: 0.73 (0.67-0.80). Results were similar for combined disability and
      mortality. Effects were largely consistent across subgroups based on age, gender,
      race, body mass index, prior hospitalization, and selected chronic conditions. In
      the presence of multiple other risk factors for disability, gait speed
      significantly increased the area under the receiver operator characteristic
      curve. CONCLUSION: In older adults, gait speed predicts 3 year incidence of
      bathing or dressing dependence, mobility difficulty, and a composite outcome of
      disability and mortality.

PMID- 26297945
TI  - Exploring the evolution of marine invertebrate cryopreservation - Landmarks,
      state of the art and future lines of research.
AB  - Lanan (1971) working on oyster sperm and Asahina and Takahashi (1977) on sea
      urchin sperm and embryos can be considered the pioneers in marine invertebrate
      cryopreservation. It was from the 90s onwards when the number of references began
      to increase and diversify not only the range of species of interest but also in
      the cell types and fields of application. This work is an attempt to summarize
      the research published on marine invertebrates in a wide variety of journals
      regarding the development and the applications of marine invertebrate
      cryopreservation protocols. This paper reviews factors and trends, the obtained
      results, remaining technical constraints and the immediate future of marine
      invertebrate cryopreservation. 

PMID- 26297946
TI  - The crucial role of zona pellucida in cryopreservation of oocytes by
      vitrification.
AB  - Mammalian oocytes have a proteinaceous hydrogel-like outer shell known as the
      zona pellucida (ZP) that semi-encloses their plasma membrane and cytoplasm. In
      this study, we cryopreserved mouse oocytes either with or without ZP by
      vitrification. Our results show that the presence of an intact ZP could
      significantly improve the post-vitrification survival of oocytes to 92.1% from
      13.3% for oocytes without ZP. Moreover, there was no significant difference in
      embryonic development between fresh and cryopreserved oocytes with ZP after in
      vitro fertilization (IVF). Further atomic force microscopy (AFM) analysis showed
      that the intact oocytes with ZP have an elastic modulus that is more than 85
      times higher than that of oocytes without ZP. This may partially explain the
      important role of ZP in protecting the oocytes by resisting the mechanical stress
      due to possible ice formation during cryopreservation by vitrification.
      Collectively, this study reveals a new biophysical role of ZP during
      vitrification of oocytes and suggests microencapsulation of the many mammalian
      cells without a ZP in ZP-like hydrogel is an effective strategy to improve their
      survival post cryopreservation by vitrification. 

PMID- 26297947
TI  - Progranulin plays crucial roles in preserving bone mass by inhibiting TNF-alpha
      induced osteoclastogenesis and promoting osteoblastic differentiation in mice.
AB  - A close correlation between atherosclerosis, inflammation, and osteoporosis has
      been recognized, although the precise mechanism remains unclear. The growth
      factor progranulin (PGRN) is expressed in various cells such as macrophages,
      leukocytes, and chondrocytes. PGRN plays critical roles in a variety of diseases,
      such as atherosclerosis and arthritis by inhibiting Tumor Necrosis Factor-alpha
      (TNF-alpha) signaling. The purpose of this study was to investigate the effect of
      PGRN on bone metabolism. Forty-eight-week old female homozygous PGRN knockout
      mice (PGRN-KO) (n = 8) demonstrated severe low bone mass in the distal femur
      compared to age- and sex-matched wild type C57BL/6J mice (WT) (n = 8) [BV/TV (%):
      5.8 vs. 16.6; p < 0.001, trabecular number (1/mm): 1.6 vs. 3.8; p < 0.001]. In
      vitro, PGRN inhibited TNF-alpha-induced osteoclastogenesis from spleen cells of
      PGRN-KO mice. Moreover, PGRN significantly promoted ALP activity, osteoblast
      related mRNA (ALP, osteocalcin) expression in a dose-dependent manner and up
      regulated osteoblastic differentiation by down-regulating phosphorylation of
      ERK1/2 in mouse calvarial cells. In conclusion, PGRN may be a promising treatment
      target for both atherosclerosis and inflammation-related osteoporosis.

PMID- 26297948
TI  - Identification of a PEAK1/ZEB1 signaling axis during TGFbeta/fibronectin-induced
      EMT in breast cancer.
AB  - Transforming Growth Factor beta (TGFbeta) is the archetypal member of the TGFbeta
      superfamily of ligands and has pleiotropic functions during normal development,
      adult tissue homeostasis and pathophysiological processes such as cancer. In
      epithelial cancers TGFbeta signaling can either suppress tumor growth or promote
      metastasis via the induction of a well-characterized epithelial-mesenchymal
      transition (EMT) program. We recently reported that PEAK1 kinase mediates
      signaling cross talk between TGFbeta receptors and integrin/Src/MAPK pathways and
      functions as a critical molecular regulator of TGFbeta-induced breast cancer cell
      proliferation, migration, EMT and metastasis. Here, we examined the breast cancer
      cell contexts in which TGFbeta induces both EMT and PEAK1, and discovered this
      event to be unique to oncogene-transformed mammary epithelial cells and triple
      negative breast cancer cells. Using the Cancer BioPortal database, we identified
      PEAK1 co-expressors across multiple malignancies that are also common to the
      TGFbeta response gene signature (TBRS). We then used the ScanSite database to
      identify predicted protein-protein binding partners of PEAK1 and the PEAK1-TBRS
      co-expressors. Analysis of the Cytoscape interactome and Babelomics-derived gene
      ontologies for a novel gene set including PEAK1, CRK, ZEB1, IL11 and COL4A1
      enabled us to hypothesize that PEAK1 may be regulating TGFbeta-induced EMT via
      its interaction with or regulation of these other genes. In this regard, we have
      demonstrated that PEAK1 is necessary for TGFbeta to induce ZEB1-mediated EMT in
      the context of fibronectin/ITGB3 activation. These studies and future mechanistic
      studies will pave the way toward identifying the context in which TGFbeta
      blockade may significantly improve breast cancer patient outcomes. 

PMID- 26297949
TI  - Time-fixed feeding prevents obesity induced by chronic advances of light/dark
      cycles in mouse models of jet-lag/shift work.
AB  - Recent findings have uncovered intimate relationships between circadian clocks
      and energy metabolism. Epidemiological studies have shown that the frequency of
      obesity and metabolic disorders increases among shift-workers. Here we found that
      a chronic shift in light/dark (LD) cycles comprising an advance of six hours
      twice weekly, induced obesity in mice. Under such conditions that imitate jet
      lag/shift work, body weight and glucose intolerance increased, more fat
      accumulated in white adipose tissues and the expression profiles of metabolic
      genes changed in the liver compared with normal LD conditions. Mice fed at a
      fixed 12 h under the LD shift notably did not develop symptoms of obesity despite
      isocaloric intake. These results suggest that jet lag/shift work induces obesity
      as a result of fluctuating feeding times and it can be prevented by fixing meal
      times. This rodent model of obesity might serve as a useful tool for
      understanding why shift work induces metabolic disorders.

PMID- 26297950
TI  - Differential caspase activity in the cortex and striatum with chronic infusion of
      3-nitropropionic acid.
AB  - Systemic administration of 3-nitropropionic acid (3-NP) facilitates the
      development of select striatal lesions, and some reports provide clues about this
      pathology. In this study, we investigated the relationship between reduced levels
      of brain-derived neurotrophic factor (BDNF) in lesioned brain regions and caspase
      activity, as well as involvement of apoptosis signal-regulating kinase 1 (ASK1)
      in caspase activation. We analyzed apoptotic cell death, BDNF distribution,
      caspase-3 activity, caspase-6 activity, ASK1 expression level, and active ASK1 in
      the cortex and striatum. There were different levels and distributions of these
      factors within each sub-region. Caspase-6 activity was reduced with down
      regulation of ASK1 in the cortex. BDNF protein levels did not decrease in the
      cortex, but there was replenishment of severely reduced BDNF in the striatum. The
      present study suggests that an increase in ASK1 in the damaged cortex is related
      to caspase-6 activation and is involved in cortical depletion of BDNF in the
      striatum. Furthermore, with systemic infusion of 3-NP, differential expression of
      ASK1 in the cortex and striatum suggests that this kinase may modulate caspase
      activation and striatal degeneration. 

PMID- 26297951
TI  - Cytotoxicity of pregnane glycosides of Cynanchum otophyllum.
AB  - Fourteen new pregnane glycosides, including nine caudatin glycosides (1-9), three
      qinyangshengenin glycosides (10-12), one kidjoranin glycosides (13) and one
      gagaminin glycosides (14), along with twelve known analogs (15-26) were isolated
      from roots of Cynanchum otophyllum Schneid. Their structures were deduced by
      detailed analysis of 1D and 2D NMR spectra, as well as HRESIMS. In this study,
      all pregnane glycosides obtained (1-26) were evaluated for their cytotoxic
      activities using three cancer cell lines (HepG2, Hela, U251). As results, except
      6 and 10, other twenty-four pregnane glycosides showed cytotoxicities at
      different degrees against three cell lines. 

PMID- 26297952
TI  - Quercetin reduced inflammation and increased antioxidant defense in rat adjuvant
      arthritis.
AB  - Novel therapies for rheumatoid arthritis also include the use of naturally
      occurring compounds possessing antioxidant properties. In the present work, the
      effects of oral administration of quercetin were investigated in a rat model of
      adjuvant arthritis. Arthritis was induced by a single intradermal injection of
      heat-inactivated Mycobacterium butyricum in incomplete Freund's adjuvant. The
      experimental groups were treated with an oral daily dose of 150 mg/kg b.w. of
      quercetin for 28 days. Results indicated that quercetin was able to ameliorate
      all markers of inflammation and oxidative stress measured. Quercetin lowered
      levels of interleukin-1beta, C-reactive protein, and monocyte chemotactic protein
      1 and restored plasma antioxidant capacity. In addition, quercetin inhibited the
      enzymatic activity of pro-inflammatory 12/15-lipoxygenase in lung and liver and
      increased the expression of heme oxygenase-1 in joint and lung of arthritic rats.
      Finally, quercetin inhibited the 2-fold increase of NF-?B activity observed in
      lung, liver and joint after induction of arthritis. 

PMID- 26297953
TI  - Early detection of Toxoplasma gondii-infected cats by interferon-gamma release
      assay.
AB  - Felines, the only definitive hosts that shed the environmentally-durable oocysts,
      are the key in the transmission of Toxoplasma gondii to all warm-blooded animals.
      They seroconvert as late as the third week and begin to shed oocysts as early as
      3-8 days after being fed tissue cysts. Early detection of Toxoplasma-infected
      cats is crucial to evaluate Toxoplasma-contaminated environment and potential
      risks to public health. Moreover, it is fundamental for Toxoplasma infection
      control. Interferon-gamma release assay (IGRA) is a blood-based test assessing
      the presence of IFN-gamma released by the T-lymphocytes directed against specific
      antigens, which is an ideal assay for early detection of Toxoplasma-infected
      cats. Here, cats were orally infected with the tissue cysts and blood was
      collected for toxoplasmic antigen stimulation, and the released IFN-gamma was
      measured by ELISA. Results showed that Toxoplasma-infection was detected by IGRA
      as early as 4 days post-infection (dpi); while serum Toxoplasma IgM and IgG were
      detected by ELISA at 10 dpi and 14 dpi, respectively. Our findings demonstrated
      that IGRA-positive and ELISA-negative samples revealed an early Toxoplasma
      infection in cats, indicating a new strategy for the early diagnosis of
      Toxoplasma infection by combining IGRA and ELISA. Therefore, IGRA could emerge as
      a reliable diagnostic tool for the exploration of cat toxoplasmosis prevalence
      and its potential risks to public health. 

PMID- 26297954
TI  - Clinical, haematological, cytokine and acute phase protein changes during
      experimental Babesia gibsoni infection of beagle puppies.
AB  - Babesia gibsoni is a haemoprotozoan parasite of emerging global importance. The
      clinical presentation of babesial infections is diverse and the systemic
      inflammatory response induced by infection is considered to be a major feature of
      the pathophysiology of canine babesiosis. An experimental case-controlled
      longitudinal study was conducted to assess the clinical, haematological, cytokine
      and acute phase protein changes that occur during experimental B. gibsoni
      infection of beagle puppies. Infected dogs became transiently pyrexic and
      anaemic, intermittently neutropenic and transiently, but profoundly,
      thrombocytopenic, although this had no apparent adverse clinical effect.
      Experimental B. gibsoni infection also induced an acute phase response,
      characterised by a marked increase in the concentration of C-reactive protein,
      which was delayed in onset following infection but preceded the detection of
      peripheral parasitaemia. Experimental B. gibsoni infection was also associated
      with marked increases in the concentration of multiple cytokines which were also
      delayed in onset following infection and occurred subsequent to the detection of
      peripheral parasitaemia and the acute phase response. This study furthers our
      understanding of the immune response that occurs during babesial infections and
      the role that systemic inflammation plays in the pathophysiology of canine
      babesiosis. 

PMID- 26297955
TI  - Balamuthia mandrillaris: Further morphological observations of trophozoites by
      light, scanning and transmission electron microscopy.
AB  - Additional morphological features of Balamuthia mandrillaris observed by light
      and electron microscopy are reported. Trophozoites were extremely pleomorphic:
      their cell shapes ranged from rounded to elongated and sometimes they appeared
      exceptionally stretched out and branched. By transmission electron microscopy it
      was possible to observe two different cytoplasmic areas, the ectoplasm and the
      endoplasm and often sections of rough endoplasmic reticulum were found in the
      transition zone. The cytoplasm was very fibrogranular and most of the organelles
      typically found in eukaryotic cells were observed. A particular finding was the
      presence of numerous mitochondria with a different structure from those of other
      free-living amoebae. The observations reported here may reinforce the
      morphological knowledge of this amoeba and provide a background for further
      analyses. 

PMID- 26297957
TI  - Use of a two-step ultrafiltration procedure to concentrate viral hemorrhagic
      septicemia virus (VHSV) in seawater.
AB  - Viral hemorrhagic septicemia virus (VHSV) has been reported to be stable in both
      fresh as well as seawater, suggesting that VHSV exists in natural aquatic
      environments and might have an effect on the wild and cultured fish. However,
      VHSV is below the detectable limits of laboratory tests in natural seawater. In
      this study, a two-step ultrafiltration (UF) procedure was used to concentration
      of VHSV in seawater, providing samples that were tested for infectivity by cell
      culture and the presence of VHSV by quantitative reverse transcriptase PCR (qRT
      PCR) methods. Overall, VHSV was approximately concentrated 100-1000 times in 1, 5
      and 10 L, seawater volumes respectively: from 2.81*10(6) to 6.53*10(7)/mL and
      10(3.3) to 10(3.8)TCID50/mL prior to the UF procedure, to 3.78*10(8), 1.16 *
      10(11), and 9.12 * 10(10)/mL after the procedure. This is the first report of
      concentrating VHSV using an UF method that was specifically designed for seawater
      samples. In addition, the two-step UF procedure appears to be compatible with
      viral cell culture and qRT-PCR methods. 

PMID- 26297956
TI  - MiR-145, a microRNA targeting ADAM17, inhibits the invasion and migration of
      nasopharyngeal carcinoma cells.
AB  - MiR-145 is downregulated and functions as a tumor suppressor in many
      malignancies. In this study, the biological function, molecular mechanism, and
      direct target genes of miR-145 in nasopharyngeal carcinoma (NPC) cells were
      investigated. Cell survival was detected by cell viability assay, and cell cycle
      was determined through flow cytometry. Invasion and migration of NPC cells were
      examined using cell invasion and wound healing assays, respectively. A
      disintegrin and metalloproteinase 17 (ADAM17) was verified as the target of miR
      145 through luciferase reporter assay, qRT-PCR, and Western blot analysis. In NPC
      cell lines, miR-145 expression was significantly downregulated and ADAM17 protein
      expression was upregulated. ADAM17 was downregulated at the post-transcriptional
      level by miR-145 via the binding site of ADAM17-3'UTR. Transfection with miR-145
      mimic suppressed cell growth and induced cell cycle arrest in the G0/G1 phase by
      upregulating key G0/G1 phase regulators, namely, p53 and p21. MiR-145 also
      inhibited cellular migration and invasion through targeting ADAM17 involving the
      regulation of EGFR and E-cadherin. Knockdown of ADAM17 elicited similar effects
      to that of miR-145 on NPC cells. This study reveals that miR-145 suppressed the
      invasion and migration of NPC cells by targeting ADAM17. Thus, miR-145 could be a
      therapeutic target for NPC.

PMID- 26297958
TI  - Construction of an oral vaccine for transmissible gastroenteritis virus based on
      the TGEV N gene expressed in an attenuated Salmonella typhimurium vector.
AB  - This research aimed to develop an oral vaccine for transmissible gastroenteritis
      virus (TGEV) based on the TGEV N gene expressed in an attenuated Salmonella
      typhimurium vector and aimed to evaluate the vaccine's immune response in
      piglets. Recombinant plasmid pVAX-N was transformed into competent cells of
      attenuated S. typhimurium SL7207 via electroporation. After it was identified via
      RT-PCR and double digestion, the screened recombinant bacteria presenting pVAX-N
      were named SL7207 (pVAX-N). To evaluate the safety and stability of the developed
      vaccine, different dosages (5 * 10(8), 1 * 10(9), and 2 * 10(9) CFU/mice) of
      SL7207 (pVAX-N) were inoculated to 6-week-old mice. Piglets below 20 days of age
      were dosed with 1 * 10(12) CFU. Humoral (neutralization titer and specific IgG),
      cellular (interleukin-4, gamma-interferon, and peripheral lymphocyte
      proliferation), and mucosal (sIgA) immune responses were detected and evaluated.
      The three immunizing dosages were determined to be safe for mice and were
      completely eliminated 8 weeks after the first inoculation. Results of antibody
      and cytokine detection indicated that SL7207 (pVAX-N) could significantly induce
      antibody-IgG, antibody-IgA, interleukin-4, and gamma-interferon, whose value was
      maximized on the 6th week. Results confirmed that the recombinant vaccine
      increased the proliferation of peripheral T lymphocyte. In conclusion, the oral
      vaccine was developed successfully, and the vaccine could significantly induce
      humoral, cellular, and mucosal immune responses in piglets.

PMID- 26297959
TI  - Use of embryonated chicken egg as a model to study the susceptibility of avian
      influenza H9N2 viruses to oseltamivir carboxylate.
AB  - Avian influenza (AI) H9N2 viruses are endemic in many bird species, and human
      infections of H9N2 viruses have been reported. Oseltamivir phosphate
      (Tamiflu((r))) is the available antiviral drug for the treatment and prophylaxis
      of influenza. There are no reports of use of embryonated chicken egg as a model
      to study susceptibility of AI viruses to oseltamivir carboxylate (OC), the active
      metabolite. The present study was undertaken to explore the use of embryonated
      chicken eggs as a model for testing OC against the AI H9N2 viruses. A total of
      three AI H9N2 viruses, isolated in poultry in India, were used. Various virus
      dilutions were tested against 14MUg/ml of OC. Three methods, namely (1) the in
      vitro virus-drug treatment, (2) drug delivery and virus challenge by allantoic
      route, and (3) drug delivery by albumen route and virus challenge by allantoic
      route were explored. The viruses were also tested using the fluorescence-based
      neuraminidase inhibitor (NAI) assay. There was significant inhibition (p<0.05) of
      the H9N2 viruses in presence of OC. The infectious virus titers as well as
      hemagglutination titers were significantly lower in presence of OC as compared to
      controls. The in vitro treatment of virus and drug; and drug and virus delivery
      at the same time by allantoic route showed significantly higher inhibition
      (p<0.05) of virus growth than that by the albumen route. In the NAI assay, the
      half maximal inhibitory concentration (IC50) values of the H9N2 viruses were
      within the standard range for known susceptible reference virus. In conclusion,
      the H9N2 viruses used in the study were susceptible to OC. Embryonated chicken
      egg could be used as a model to study susceptibility of AI viruses to antiviral
      drugs. 

PMID- 26297960
TI  - Performance of the HPV-16 L1 methylation assay and HPV E6/E7 mRNA test for the
      detection of squamous intraepithelial lesions in cervical cytological samples.
AB  - HPV-16 L1 methylation and E6/E7 mRNA have suggested that they had close
      relationship with cervical neoplastic progression. This study aimed to evaluate
      the clinical performance of the HPV-16 L1 methylation assay and E6/E7 mRNA test
      for detecting high-grade cervical lesions (CIN2+). A total of 81 women with
      liquid-based cytology (LBC) samples, histological results, and positive HPV-DNA
      test for HPV type 16 only were included in this study. HPV-16 L1 methylation and
      E6/E7 mRNA levels were measured using methylation-sensitive high resolution
      melting (MS-HRM) analysis and Quantivirus(r)HPV E6/E7 RNA 3.0 assay (bDNA),
      respectively, in the same residue of LBC samples. The current date showed a
      positive correlation between the HPV-16 L1 methylation and the E6/E7 mRNA levels.
      The L1 methylation and mRNA levels both increased with disease severity. The mRNA
      test method showed higher sensitivity and NPV (98.0 and 91.7% vs. 89.8 and
      80.8%), while lower specificity and PPV (34.4 and 69.6% vs. 65.6 and 80.0%), than
      the L1 methylation assay for detecting histology-confirmed CIN2+. When using the
      detection method of mRNA test combined with L1 methylation assay, we obtained a
      sensitivity of 89.8% and a specificity of 71.9%. These findings suggest that
      assessment of HPV-16 L1 methylation testing combined with E6/E7 mRNA testing may
      be a promising method for the triage of women with HPV type 16 only. 

PMID- 26297961
TI  - Pharmacokinetic analysis of prostate cancer using independent component analysis.
AB  - Dynamic contrast enhanced (DCE)-MRI combined with pharmacokinetic (PK) modeling
      of a tumor provides information about its perfusion and vascular permeability.
      Most PK models require the time course of contrast agent concentration in blood
      plasma as an input, which cannot be measured directly at the tissue of interest,
      and is approximated with an arterial input function (AIF). Variability in methods
      used in estimating the AIF and inter-observer variability in region of interest
      selection are major sources of discrepancy between different studies. This study
      had two aims. The first was to determine whether a local vascular input function
      (VIF) estimated using an adaptive complex independent component analysis (AC-ICA)
      algorithm could be used to estimate PK parameters from clinical dynamic contrast
      enhanced (DCE)-MRI studies. The second aim was to determine whether normalizing
      the input function using its area under the curve would improve the results of PK
      analysis. AC-ICA was applied to DCE-MRI of 27 prostate cancer patients and the
      intravascular signal was estimated. This signal was converted into contrast agent
      concentration to give a local vascular input function (VIF) which was used as the
      input function for PK analysis. We compared K(trans) values for normal peripheral
      zone (PZ) and tumor tissues using the local VIF with those calculated using a
      conventional AIF obtained from the femoral artery. We also compared the K(trans)
      values obtained from the un-normalized input functions with the KN(trans) values
      obtained after normalizing the AIF and local VIF. Normalization of the input
      function resulted in smaller variation in PK parameters (KN(trans) vs. K(trans)
      for normal PZ tissue was 0.20+/-0.04mM.min(-1) vs. 0.87+/-0.54min(-1) for local
      VIF and 0.21+/-0.07mM.min(-1) vs. 0.25+/-0.29min(-1) for AIF) and better
      separation of the normal and tumor tissues (effect-size of this separation using
      KN(trans) vs. K(trans) was 0.89 vs. 0.75 for local VIF and 0.94 vs. 0.41 for
      AIF). The AC-ICA and AIF-based analyses provided similar (KN(trans)) values in
      normal PZ tissue of prostate across patients. Normalizing the input function
      before PK analysis significantly improved the reproducibility of the PK
      parameters and increased the separation between normal and tumor tissues. Using
      AC-ICA allows a local VIF to be estimated and the resulting PK parameters are
      similar to those obtained using a more conventional AIF; this may be valuable in
      studies where an artery is not available in the field of view. 

PMID- 26297962
TI  - Design of a miRNA sponge for the miR-17 miRNA family as a therapeutic strategy
      against vulvar carcinoma.
AB  - Dysregulation of microRNAs has been studied thoroughly, and has been observed in
      a variety of tumors including vulvar carcinomas, a rare type of gynecological
      tumor with increasing incidence. However, very few therapeutic alternatives have
      reached the clinical setting, and there is an urgent unmet need to develop novel
      strategies for patients with this tumor type. Thus, a microRNA (miRNA) sponge for
      the miR-17 miRNA family was designed, synthesized and validated in vitro in order
      to explore a new therapeutic strategy based on inhibiting this oncogenic miRNA
      family in vulvar cancer. Members of the miR-17 family were evaluated for
      expression in a vulvar tumor cell line (SW954) and 20 HPV negative formalin-fixed
      paraffin-embedded (FFPE) samples by quantitative real-time PCR (qRT-PCR). Six in
      tandem, bulged sequences that were complementary to these miRNAs were designed,
      synthesized, cloned, and transfected into SW954 cells. A luciferase reporter
      assay with a psiCheck2 vector was used to test the specificity of the sponge
      sequences for miR-17 family miRNA binding. Taqman qRT-PCR was used to test how
      the sponges affected miRNA expression. In FFPE samples, higher expression of miR
      20a and miR-106a correlated with deeper tumor invasion (P = 0.0187 and P =
      0.0404, respectively). The luciferase reporter assay validated the specificity of
      the sponge for miR-17 family members. Using qRT-PCR, we confirmed this
      specificity with decreased expression in 5 (out of six) miRNAs of the miR-17
      family in SW954 cells. Although our results are preliminary, these results
      demonstrate that these miRNA sponges are potent inhibitors of the miR-17 family
      of miRNAs in SW954. Therefore, this miRNA-specific sponge may be developed into a
      novel therapeutic treatment for patients with vulvar cancer.

PMID- 26297963
TI  - AMPK and autophagy in glucose/glycogen metabolism.
AB  - Glucose/glycogen metabolism is a primary metabolic pathway acting on a variety of
      cellular needs, such as proliferation, growth, and survival against stresses. The
      multiple regulatory mechanisms underlying a specific metabolic fate have been
      documented and explained the molecular basis of various pathophysiological
      conditions, including metabolic disorders and cancers. AMP-activated protein
      kinase (AMPK) has been appreciated for many years as a central metabolic
      regulator to inhibit energy-consuming pathways as well as to activate the
      compensating energy-producing programs. In fact, glucose starvation is a potent
      physiological AMPK activating condition, in which AMPK triggers various
      subsequent metabolic events depending on cells or tissues. Of note, the recent
      studies show bidirectional interplay between AMPK and glycogen. A growing number
      of studies have proposed additional level of metabolic regulation by a lysosome
      dependent catabolic program, autophagy. Autophagy is a critical degradative
      pathway not only for maintenance of cellular homeostasis to remove potentially
      dangerous constituents, such as protein aggregates and dysfunctional subcellular
      organelles, but also for adaptive responses to metabolic stress, such as nutrient
      starvation. Importantly, many lines of evidence indicate that autophagy is
      closely connected with nutrient signaling modules, including AMPK, to fine-tune
      the metabolic pathways in response to many different cellular cues. In this
      review, we introduce the studies demonstrating the role of AMPK and autophagy in
      glucose/glycogen metabolism. Also, we describe the recent advances on their
      contributions to the metabolic disorders. 

PMID- 26297964
TI  - The effects of the cellular and infectious prion protein on the neuronal adaptor
      protein X11alpha.
AB  - BACKGROUND: The neuronal adaptor protein X11alpha is a multidomain protein with a
      phosphotyrosine binding (PTB) domain, two PDZ (PSD_95, Drosophila disks-large, ZO
      1) domains, a Munc Interacting (MI) domain and a CASK interacting region. Amongst
      its functions is a role in the regulation of the abnormal processing of the
      amyloid precursor protein (APP). It also regulates the activity of Cu/Zn
      Superoxide dismutase (SOD1) through binding with its chaperone the copper
      chaperone for SOD1. How X11alpha production is controlled has remained unclear.
      METHODS: Using the neuroblastoma cell line, N2a, and knockdown studies, the
      effect of the cellular and infectious prion protein, PrP(C) and PrP(Sc), on
      X11alpha is examined. RESULTS: We show that X11alpha expression is directly
      proportional to the expression of PrP(C), whereas its levels are reduced by
      PrP(Sc). We also show PrP(Sc) to affect X11alpha at a functional level. One of
      the effects of prion infection is lowered cellular SOD1 levels, here by knockdown
      of X11alpha we identify that the effect of PrP(Sc) on SOD1 can be reversed
      indicating that X11alpha is involved in prion disease pathogenesis. CONCLUSIONS:
      A role for the cellular and infectious prion protein, PrP(C) and PrP(Sc),
      respectively, in regulating X11alpha is identified in this work. GENERAL
      SIGNIFICANCE: Due to the multiple interacting partners of X11alpha, dysfunction
      or alteration in X11alpha will have a significant cellular effect. This work
      highlights the role of PrP(C) and PrP(Sc) in the regulation of X11alpha, and
      provides a new target pathway to control X11alpha and its related functions.

PMID- 26297965
TI  - Rare sugar D-allulose: Potential role and therapeutic monitoring in maintaining
      obesity and type 2 diabetes mellitus.
AB  - Obesity and type 2 diabetes mellitus (T2DM) are the leading worldwide risk
      factors for mortality. The inextricably interlinked pathological progression from
      excessive weight gain, obesity, and hyperglycemia to T2DM, usually commencing
      from obesity, typically originates from overconsumption of sugar and high-fat
      diets. Although most patients require medications, T2DM is manageable or even
      preventable with consumption of low-calorie diet and maintaining body weight.
      Medicines like insulin, metformin, and thiazolidinediones that improve glycemic
      control; however, these are associated with weight gain, high blood pressure, and
      dyslipidemia. These situations warrant the attentive consideration of the role of
      balanced foods. Recently, we have discovered advantages of a rare sugar, D
      allulose, a zero-calorie functional sweetener having strong anti-hyperlipidemic
      and anti-hyperglycemic effects. Study revealed that after oral administration in
      rats D-allulose readily entered the blood stream and was eliminated into urine
      within 24h. Cell culture study showed that D-allulose enters into and leaves the
      intestinal enterocytes via glucose transporters GLUT5 and GLUT2, respectively. In
      addition to D-allulose's short-term effects, the characterization of long-term
      effects has been focused on preventing commencement and progression of T2DM in
      diabetic rats. Human trials showed that D-allulose attenuates postprandial
      glucose levels in healthy subjects and in borderline diabetic subjects. The anti
      hyperlipidemic effect of D-allulose, combined with its anti-inflammatory actions
      on adipocytes, is beneficial for the prevention of both obesity and
      atherosclerosis and is accompanied by improvements in insulin resistance and
      impaired glucose tolerance. Therefore, this review presents brief discussions
      focusing on physiological functions and potential benefits of D-allulose on
      obesity and T2DM.

PMID- 26297967
TI  - How does the hippocampus shape decisions?
AB  - Making optimal decisions depends on an appreciation of the value of choices. An
      important source of information about value comes from memory for prior
      experience. Such value-based learning has historically been considered the domain
      of a striatal memory system. However, recent developments suggest that memorial
      representations supported by the hippocampus may also contribute to decision
      making. Unlike striatal representations, hippocampal ones are flexible; they can
      be modified and updated as new information is acquired. In this paper we argue
      that the hippocampus plays a pivotal role in value-based decision making via
      three flexible learning mechanisms: (1) updating, (2) generalization, and (3)
      construction. 

PMID- 26297966
TI  - Roles of receptor for activated protein kinase C1 for modulating immune responses
      in white shrimp Litopenaeus vannamei.
AB  - Complementary (c)DNA encoding a receptor for activated protein kinase C1 (RACK1)
      messenger (m)RNA of the white shrimp Litopenaeus vannamei, designated LvRACK1,
      consisted a 1136-bp cDNA containing an open reading frame (ORF) of 954 bp, a 111
      bp 5'-untranslated region (UTR), and a 71-bp 3'-UTR, which is a 36 kDa cytosolic
      protein, belonging to the Trp-Asp40 (WD40) family of proteins, characterized by
      containing seven highly conserved Trp-Asp40 (WD40) internal repeats, and a poly A
      tail. The WD repeat of LvRACK1 can be predicted to form a seven-bladed propeller
      structure with each WD repeat composed of four antiparallel beta-sheets. The WD40
      domains have been implicated in protein-protein interactions. A comparison of
      amino acid sequences showed that LvRACK1 was closely related to arthropods RACK1.
      LvRACK1 cDNA was synthesized in all tested tissues detected with real-time PCR
      including haemocytes, hepatopancreas, gills, muscles, subcuticular epithelium,
      intestines, abdominal nervous ganglia, thoracic nervous ganglia, lymphoid organ,
      stomach, heart, and antennal gland, especially in subcuticular epithelium and
      gill. LvRACK1 mRNA transcription in haemocytes of L. vannamei injected with
      Vibrio alginolyticus decreased. The depletion of LvRACK1 of haemocytes in L.
      vannamei received its dsRNA revealed the increased respiratory bursts per
      haemocyte, superoxide dismutase (SOD), activity, glutathione peroxidase (GPx)
      activity, and clotting time, but showed the decreased total haemocyte count
      (THC), hyaline cells (HCs), phagocytic activity, and transglutaminase (TG)
      activity. LvRACK1 silenced shrimp showed the upregulated gene expressions of
      cyMnSOD, mtMnSOD, peroxinectin (PE), and TGI, and showed the downregulated alpha2
      macroglobulin (alpha2-M), clottable protein (CP), lysozyme, and crustin gene
      expressions. It is therefore concluded that LvRACK1 is involved in immune defense
      and signaling transduction in haemocytes of L. vannamei infected with V.
      alginolyticus.

PMID- 26297968
TI  - Latent Class Analysis of the Short and Long Forms of the Chronic Pain Acceptance
      Questionnaire: Further Examination of Patient Subgroups.
AB  - A substantial literature indicates that pain acceptance is a useful behavioral
      process in chronic pain rehabilitation. Pain acceptance consists of willingness
      to experience pain and to engage in important activities even in the presence of
      pain and is often measured using the Chronic Pain Acceptance Questionnaire
      (CPAQ). Previous traditional cluster analyses of the 20-item CPAQ identified 3
      patient clusters that differed across measures of patient functioning in
      meaningful ways. The aims of this study were to replicate the previous study in a
      new sample, using the more robust method of latent class analysis (LCA), and to
      compare the cluster structure of the CPAQ and the shorter CPAQ-8. In total, 914
      patients with chronic pain completed the CPAQ and a range of measures of
      psychological and physical function. Patient clusters identified via LCA were
      then used to compare patients across functional measures. Contrary to previous
      research, LCA demonstrated that a 4-cluster structure was superior to a 3-cluster
      structure. Consistent with previous research, cluster membership based on
      patterns of pain willingness and activity engagement was significantly associated
      with specific patterns of psychological and physical function, in line with
      theoretical predictions. These cluster structures were similar for both CPAQ-20
      and CPAQ-8 items. These results provide further evidence of the relevance of
      chronic pain acceptance, and a more nuanced understanding of how the components
      of acceptance are related to function. PERSPECTIVE: Pain acceptance is important
      in chronic pain. The findings of the present study, which included 914
      individuals with chronic pain, provide support for 4 discrete groups of patients
      based on levels of acceptance (low, medium, and high), as well as a group with a
      high level of activity engagement and low willingness to have pain. These groups
      appear statistically robust and differed in predictable ways across measures of
      functioning.

PMID- 26297969
TI  - An alternative to MOC?

PMID- 26297970
TI  - Bridging the G-APP: Continuous Professional Development for Gastroenterologists:
      Replacing MOC with a Model for Lifelong Learning and Accountability.

PMID- 26297971
TI  - Hysteroscopic Curettage Using the Lin Snare and Y Adaptor: A Review of 300 Cases.
AB  - STUDY: To present a de novo technique of endometrial sampling - hysteroscopic
      curettage. OBJECTIVE: Aim to describe this new procedure and study its
      effectiveness and accuracy. DESIGN: Prospective study (Canadian Task Force
      Classification II-2). SETTING: University-affiliated public hospital. PATIENTS:
      Two hundred and ninety-three consecutive patients who attended outpatient
      gynaecological endoscopic centre. INTERVENTION: A total of 300 hysteroscopic
      curettage was carried out using flexible hysteroscope and Lin snare system. MAIN
      RESULTS: The procedure failure rate is 2.67%. Out of 292 successful hysteroscopic
      curettages, hysteroscopy alone has a sensitivity of 99% and negative predictive
      value of 97.7%. The accuracy was further improved to near perfection with
      curettage histology. The negative predictive value is 99%. CONCLUSION:
      Hysteroscopic curettage is easy to perform, highly effective and accurate. It
      offers an excellent outpatient alternative for patients who require endometrial
      sampling and/or an evaluation of abnormal uterine bleeding.

PMID- 26297972
TI  - 4-Nerolidylcatechol analogues as promising anticancer agents.
AB  - 4-Nerolidylcatechol (1) is an isolated compound from Pothomorphe umbellata L.
      (Piperaceae) with promising antitumor cells properties. However it presents
      lability under light and room temperatures. Many efforts have been directed
      towards discovering anticancer agents endowed with cytotoxic activities. Here, we
      evaluated cytotoxic effects of 4-NRC analogues (LQFMs 2-6) and the cell death
      pathways induced by these compounds in multidrug-resistant K562 cells. Compounds
      (2-6) exhibited cytotoxic activities in a concentration-dependent manner against
      leukaemic cells, specially the compounds (3) and (5). Additionally, compounds
      (1), (3) and (5) promoted marked alterations on the cell morphology, including
      nuclear changes as demonstrated by Hoescht 33342 staining. Moreover, these
      compounds promoted apoptosis induction in K562 cells by phosphatidylserine
      exposure, increase of sub-G1 cells and modulation of the caspases-3/7, -8 and -9
      activation. In addition, the pancaspase inhibitor z-VAD-fmk partially reduced the
      apoptosis induced by the compounds (1) and (5)-induced, suggesting caspase
      dependent and caspase-independent cell death pathways. Compounds (1) and (5) also
      modified the cell cycle progression by G0/G1 and S arrest, respectively.
      Furthermore, compounds (1), (3) and (5) promoted mitochondrial dysfunction
      associated to accumulation of cytosolic cytochrome c and modulated the NF-KB
      activation. In addition, unlike their analogues, 4-NRC (1) also promoted a
      significant cyclin D1 inhibition. Together, these data suggest that the mechanism
      of cell death of 4-NRC and its analogues (3) and (5) occurs by apoptosis through
      mitochondrial mechanisms. Considering that LQFMs are biocompatible synthetic
      analogues produced by molecular simplification of (1) without the chiral centre,
      which is associated with the instability found in compound (1), we suggest that
      these compounds are promising candidates for further pre-clinical studies. 

PMID- 26297973
TI  - Modulation of endoplasmic reticulum stress in Parkinson's disease.
AB  - Parkinson's disease is a neurodegenerative disease characterized by the loss of
      dopaminergic neurons in the substantia nigra in the midbrain. However, the
      etiology of the reduction in dopaminergic neurons remains unclear. Recently, it
      has been suggested that oxidative stress, endoplasmic reticulum (ER) stress, and
      mitochondrial dysfunction are involved in neuronal cell death in the pathology of
      Parkinson's disease. Furthermore, it has been suggested that some existing anti-
      Parkinson's disease drugs have protective effects against cell death. Among
      these, zonisamide exerts neuroprotective effects partly by modulating ER stress.
      Elucidating the involvement of ER stress in in vitro and in vivo Parkinson's
      disease models and investigating the mechanisms against ER stress will contribute
      to the search for new therapeutic agents for Parkinson's disease. 

PMID- 26297974
TI  - Inhibition of microglia in the basolateral amygdala enhanced morphine-induced
      antinociception: Possible role of GABAA receptors.
AB  - In clinical medicine, morphine is widely used to relieve many types of pain, but
      it has several side effects such as the development of tolerance and dependence.
      In order to decrease the side effects of morphine administration for the
      treatment of pain, the combination of minocycline as a glial inhibitor and
      morphine has been suggested in previous studies. It is important to understand
      which synaptic mechanisms are involved in the potentiative effect of minocycline
      on morphine antinociception. To this aim, male Wistar rats were bilaterally
      cannulated in the basolateral amygdala by srereotaxic instrument. A tail-flick
      apparatus was used to measure the pain threshold. The results revealed that
      intraperitoneal injection of morphine (2.5-7.5 mg/kg) induced antinociception.
      Intra-basolateral amygdala microinjection of minocycline (5-10 ug/rat) by itself
      had no effect on tail-flick latency, while the microinjection of the same doses
      of minocycline with an ineffective dose of morphine (5 mg/kg) induced
      antinociception. Intra-basolateral amygdala microinjection of different doses of
      muscimol (0.001-0.005 ug/rat) increased the minocycline-induced potentioation on
      morphine response in the tail-flick test. Intra-basolateral amygdala
      microinjection of muscimol by itself had no effect on tail-flick latency. On the
      other hand, intra-basolateral amygdala microinjection of bicuculline (0.01-0.1
      ug/rat) inhibited minocycline-induced potentiation of morphine antinociception.
      It should be noted that intra-basolateral amygdala bicucculine by itself had no
      effect on tail-flick latency. It can thus be concluded that intra-basolateral
      amygdala minocycline potentiates morphine response in the tail-flick test.
      Moreover, basolateral amygdala GABAergic system may be involved in the
      minocycline-induced potentiation of morphine response via GABAA receptors.

PMID- 26297975
TI  - beta2-adrenoceptor agonist-evoked reactive oxygen species generation in mouse
      atria: implication in delayed inotropic effect.
AB  - Fenoterol, a beta2-adrenoceptor agonist, has anti-apoptotic action in
      cardiomyocytes and induces a specific pattern of downstream signaling. We have
      previously reported that exposure to fenoterol (5 MUM) results in a delayed
      positive inotropic effect which is related to changes in both Ca2+ transient and
      NO. Here, the changes in reactive oxygen species (ROS) production in response to
      the fenoterol administration and the involvement of ROS in effect of this agonist
      on contractility were investigated in mouse isolated atria. Stimulation of beta2
      adrenoceptor increases a level of extracellular ROS, while intracellular ROS
      level rises only after removal of fenoterol from the bath. NADPH-oxidase
      inhibitor (apocynin) prevents the increase in ROS production and the Nox2 isoform
      is immunofluorescently colocalized with beta2-adrenoceptor at the atrial
      myocytes. Treatments with antioxidants (N-acetyl-L-cysteine, NADPH inhibitors,
      exogenous catalases) significantly inhibit the fenoterol induced increase in the
      contraction amplitude, probably by attenuating Ca2+ transient and up-regulating
      NO production. ROS generated in a beta2-adrenoceptor-dependent manner can
      potentiate the activity of some Ca2+ channels. Indeed, inhibition of ryanodine
      receptors, TRPV-or L-type Ca2+- channels shows a similar efficacy in reduction of
      positive inotropic effect of both fenoterol and H2O2. In addition, detection of
      mitochondrial ROS indicates that fenoterol triggers a slow increase in ROS which
      is prevented by rotenone, but rotenone has no impact on the inotropic effect of
      fenoterol. We suggest that stimulation of beta2-adrenoceptor with fenoterol
      causes the activation of NADPH-oxidase and after the agonist removal
      extracellularly generated ROS penetrates into the cell, increasing the atrial
      contractions probably via Ca2+ channels.

PMID- 26297976
TI  - Matrix metalloproteinase inhibitors prevent sepsis-induced refractoriness to
      vasoconstrictors in the cecal ligation and puncture model in rats.
AB  - Previous studies have shown that the loss of contractility in aortas from
      lipopolysaccharide (LPS)-treated rats is related to intracellular activation of
      matrix metalloproteinase (MMPs). However, the role of MMPs in the vascular
      refractoriness to vasoconstrictors has not been investigated in a model of
      polymicrobial sepsis. We evaluated the effects of the oral administration of the
      MMP inhibitors doxycycline or ONO-4817 in the in vitro vascular reactivity of
      aortic rings from rats subjected to the cecal ligation and puncture (CLP) model
      of sepsis. Both doxycycline and ONO-4817 did not change vascular responses in
      sham-operated rats, but fully prevented hyporeactivity to KCl, phenylephrine and
      angiotensin II in vessels from CLP rats. This protective effect was not
      associated with changes in hematological parameters or blood nitrate and nitrite.
      The refractoriness to contractile agents was accompanied by enhanced activity of
      MMP-2 in aorta from CLP rats, which was abrogated by MMP inhibitors. CLP-induced
      sepsis did not impair the levels of MMP-2 in aorta, but significantly reduced
      calponin-1, a regulatory protein of vascular contraction. In addition, augmented
      levels of TIMP-1 were found in vessels from CLP rats. All these differences were
      prevented by either doxycycline or ONO-4817. Our study shows, for the first time
      in the CLP rat model of sepsis, that the vascular refractoriness to different
      contractile agents induced by polymicrobial sepsis is associated with increased
      activity of MMP-2 and reduced amounts of calponin-1 in the aorta. These findings
      reinforce the importance of the enhanced activity of MMPs for vascular failure in
      septic shock. 

PMID- 26297977
TI  - The autotaxin-lysophosphatidic acid pathway in pathogenesis of rheumatoid
      arthritis.
AB  - Lysophosphatidic acid (LPA) is a phospholipid that is mainly produced by the
      hydrolysis of lysophosphatidylcholine (LPC) by lysophospholipase D, which is also
      called autotaxin (ATX). LPA interacts with specific G-protein coupled receptors
      and is involved in the regulation of cellular survival, proliferation,
      differentiation and motility. LPA also has roles in several pathological
      disorders, such as cancer and pulmonary, dermal and renal fibrosis. The
      involvement of the ATX-LPA pathway has recently been demonstrated in inflammatory
      responses and apoptosis of fibroblast-like synoviocytes (FLS) from patients with
      rheumatoid arthritis and during the development of experimental arthritis. This
      review summarises the current literature of the ATX-LPA pathway in rheumatoid
      arthritis. 

PMID- 26297978
TI  - Oleanolic acid attenuates obstructive cholestasis in bile duct-ligated mice,
      possibly via activation of NRF2-MRPs and FXR antagonism.
AB  - Obstructive cholestasis is characterized by impairment of hepatic canalicular
      bile efflux and there are no clinically effective drugs to cure except surgeries.
      Previously we revealed that oleanolic acid (OA) protected against lithocholic
      acid (LCA)-induced intrahepatic cholestasis in mice. Cholestasis caused by LCA is
      characterized by segmental bile duct obstruction, whether OA possesses the
      beneficial effect on completed obstructive cholestasis induced by bile duct
      ligation (BDL) remains unknown. In this study, we demonstrated that BDL-induced
      mice liver pathological change, and increase in serum levels of ALT, AST and ALP
      were all significantly reduced by OA (20 mg/kg, i.p.). Meanwhile, OA also lowered
      total bilirubin and total bile acids levels in serum, as well as total bile acids
      level in liver, in contrast, urinary total bile acids output was remarkably up
      regulated by OA. Gene expression analysis showed that OA caused significant
      increased mRNA expression of MRP3 and MRP4 located at hepatic basolateral
      membrane, and restoration of MRP2 and BSEP located at hepatic cannalicular
      membrane. Furthermore, significant NRF2 protein accumulation in nucleus was also
      observed in OA treated mice. In mice primary cultured hepatocytes, the effects of
      OA on MRP2, MRP3 and MRP4 expression were directly proved to be mediated via NRF2
      activation, and BSEP downregulation induced by OA was in part due to FXR
      antagonism. Luciferase assay performed in Hep G2 cells also illustrated that OA
      was a partial FXR antagonist. Taken together, we conclude that OA attenuates
      obstructive cholestasis in BDL mice, possibly via activation of NRF2-MRPs and FXR
      antagonism.

PMID- 26297979
TI  - Herbacetin inhibits inducible nitric oxide synthase via JNK and nuclear factor
      kappaB in LPS-stimulated RAW264.7 cells.
AB  - Herbacetin (3,4',5,7,8-pentahydroxyflavone), an active flavonol compound within
      flavonoid, has been shown to induce apoptosis in HepG2 cells and suppress
      hepatocyte growth factor-induced motility of human breast cancer MDA-MB-231
      cells. However, the anti-inflammatory mechanisms of Herbacetin have not been
      researched. In this study, we examined the inflammatory responses stimulated by
      lipopolysaccharide (LPS) in RAW264.7 macrophage cells after pretreatment with
      different concentrations of Herbacetin. We found that Herbacetin decreased nitric
      oxide (NO) production in LPS-induced RAW264.7 and mouse bone marrow-derived
      macrophages. In addition, Herbacetin inhibited the LPS-induced expression of
      inducible nitric oxide synthase mRNA and protein in RAW264.7 cells. Treatment
      with Herbacetin decreased the release of proinflammatory cytokines, including TNF
      alpha and IL-1beta. Moreover, Herbacetin inhibited the activity of JNK kinase and
      nuclear factor-kappaB, signaling molecules involved in NO production. Cell
      signaling analysis using Bay 11-7082 (an inhibitory kappaB kinase 2 inhibitor)
      and mitogen-activated protein kinase (MAPK) inhibitors (SB203580 for p38,
      SP600125 for JNK, and PD 98059 for ERK) suggested that LPS induced iNOS
      expression via activation of the JNK and NF-kappaB pathway, but not the p38 and
      ERK pathway. These findings suggest that Herbacetin exerts an anti-inflammatory
      effect through suppression of LPS-induced JNK and NF-kappaB signaling pathways
      and diminished production of proinflammatory cytokines and mediators. 

PMID- 26297980
TI  - CD36 initiated signaling mediates ceramide-induced TXNIP expression in pancreatic
      beta-cells.
AB  - Diverse mechanisms are involved in the pathogenesis of beta-cell failure in type
      2 diabetes. Of them, the accumulation of ceramide, a bioactive lipid metabolite,
      is suggested to play a major role in inflammatory and stress responses that
      induce diabetes. However, the downstream inflammatory target of ceramide has not
      been defined. Using rat islets and the INS-1 beta-cell line, we hypothesized that
      activation of the redox sensitive protein TXNIP is involved in ceramide-induced
      beta-cell dysfunction. Incubation of INS-1 cells and primary islets with C2
      ceramide (N-acetyl-sphingosine) downregulated insulin and PDX-1 expression and
      increased beta-cell apoptosis. Ceramide treatment induced a time dependent
      increase in TXNIP gene expression accompanied by activation of nuclear factor
      (NF)-kappaB and reduced mitochondrial thioredoxin (TRX) activity. Pretreatment
      with sulfo-N-succinimidyl oleate (SSO), an irreversible inhibitor of the
      scavenger receptor CD36, blocked ceramide-induced up-regulation of TXNIP
      expression and activity of NF-kappaB. Blockade of NF-kappaB nuclear translocation
      by the peptide SN50 prevented ceramide-mediated TXNIP induction. Furthermore, SSO
      also attenuated ceramide-induced early loss of insulin signaling and apoptosis.
      Collectively, our results unveil a novel role of CD36 in early molecular events
      leading to NF-kappaB activation and TXNIP expression. These data suggest that
      CD36 dependent NF-kappaB-TXNIP signaling contributes to the ceramide-induced
      pathogenesis of pancreatic beta-cell dysfunction and failure. 

PMID- 26297981
TI  - Inhibition of intestinal chloride secretion by piperine as a cellular basis for
      the anti-secretory effect of black peppers.
AB  - Piperine is the principal alkaloid in black peppers (Piper nigrum L.), which is a
      commonly included spice in anti-diarrheal formulations. Piperine has
      antispasmodic activities, but its anti-secretory effect is not known. Therefore,
      this study investigated the anti-secretory effect of piperine and its underlying
      mechanism. Piperine inhibited cAMP-mediated Cl- secretion in human intestinal
      epithelial (T84) cells, similar to black pepper extract. Intraluminal
      administration of piperine (2 MUg/loop) suppressed cholera toxin-induced
      intestinal fluid accumulation by ~85% in mice. The anti-secretory mechanism of
      piperine was investigated by evaluating its effects on the activity of transport
      proteins involved in cAMP-mediated Cl- secretion. Notably, piperine inhibited
      CFTR Cl- channel activity (IC50#8'6#10 MUM) without affecting intracellular cAMP
      levels. The mechanisms of piperine-induced CFTR inhibition did not involve MRP4
      mediated cAMP efflux, AMPK or TRPV1. Piperine also inhibited cAMP-activated
      basolateral K+ channels, but it had no effect on Na+-K+-Cl- cotransporters or Na+
      K+ ATPases. Piperine suppressed Ca2+-activated Cl- channels (CaCC) without
      affecting intracellular Ca2+ concentrations or Ca2+-activated basolateral K+
      channels. Collectively, this study indicates that the anti-secretory effect of
      piperine involves the inhibition of CFTR, CaCC and cAMP-activated basolateral K+
      channels. Piperine represents a novel class of drug candidates for the treatment
      of diarrheal diseases caused by the intestinal hypersecretion of Cl-.

PMID- 26297982
TI  - Intravenous nanosomes of quercetin improve brain function and hemodynamic
      instability after severe hypoxia in newborn piglets.
AB  - Perinatal asphyxia is a major cause of death and neurological morbidity in
      newborns and oxidative stress is one of the critical mechanisms leading to
      permanent brain lesions in this pathology. In this context we have chosen
      quercetin, a natural antioxidant, known also by its brain protective effects to
      study its potential as a therapy for brain pathology provoked by severe hypoxia
      in the brain. To overcame the difficulties of quercetin to access the brain, we
      have developed lecithin/cholesterol/cyclodextrin nanosomes as a safe and
      protective vehicle. We have applied the nanosomal preparation intravenously to
      newborn piglets submitted to a severe hypoxic or ischemic/hypoxic episode and
      followed them for 8 or 72 h, respectively. Either towards the end of 8 h after
      hypoxia or up to 72 h after, electroencephalographic amplitude records in animals
      that received the nanosomes improved significantly. Animals receiving quercetin
      also stabilized blood pressure and recovered spontaneous breathing. In this
      experimental group mechanical ventilation assistance was withdrawn in the first
      24 h while the hypoxic and vehicle groups required more than 24 h of mechanical
      ventilation. Three days after the hypoxia the suckling and walking capacity in
      the group that received quercetin recovered significantly compared with the
      hypoxic groups. Pathological studies did not show significant differences in the
      brain of newborn piglets treated with nanosomes compared with hypoxic groups. The
      beneficial effects of quercetin nanosomal preparation after experimental
      perinatal asphyxia show it as a promising putative treatment for the damaged
      brain in development.

PMID- 26297983
TI  - Physiological performance of warm-adapted marine ectotherms: Thermal limits of
      mitochondrial energy transduction efficiency.
AB  - Thermal regimes in aquatic systems have profound implications for the physiology
      of ectotherms. In particular, the effect of elevated temperatures on
      mitochondrial energy transduction in tropical and subtropical teleosts may have
      profound consequences on organismal performance and population viability. Upper
      and lower whole-organism critical temperatures for teleosts suggest that
      subtropical and tropical species are not susceptible to the warming trends
      associated with climate change, but sub-lethal effects on energy transduction
      efficiency and population dynamics remain unclear. The goal of the present study
      was to compare the thermal sensitivity of processes associated with mitochondrial
      energy transduction in liver mitochondria from the striped mojarra (Eugerres
      plumieri), the whitemouth croaker (Micropogonias furnieri) and the palometa
      (Trachinotus goodei), to those of the subtropical pinfish (Lagodon rhomboides)
      and the blue runner (Caranx crysos). Mitochondrial function was assayed at
      temperatures ranging from 10 to 40 degrees C and results obtained for both
      tropical and subtropical species showed a reduction in the energy transduction
      efficiency of the oxidative phosphorylation (OXPHOS) system in most species
      studied at temperatures below whole-organism critical temperature thresholds. Our
      results show a loss of coupling between O2 consumption and ATP production before
      the onset of the critical thermal maxima, indicating that elevated temperature
      may severely impact the yield of ATP production per carbon unit oxidized. As
      warming trends are projected for tropical regions, increasing water temperatures
      in tropical estuaries and coral reefs could impact long-term growth and
      reproductive performance in tropical organisms, which are already close to their
      upper thermal limit. 

PMID- 26297984
TI  - Transformation of potential medical demand in China: A system dynamics simulation
      model.
AB  - OBJECTIVES: The increasing of potential medical demand in China has threatened
      the health of the population, the medical equity, accessibility to medical
      services, and has impeded the development of Chinese health delivery system. This
      study aims to understand the mechanism of the increasing potential medical demand
      and find some solutions. METHODS: We constructed a system dynamics model to
      analyze and simulate this problem, to predict the influences of health policies
      on the actual percentage of patients not seeking medical care (adjusting the
      quantity structure of hospitals and community health systems (CHSs), adjusting
      outpatient prices, and adjusting the level of health insurance). RESULTS:
      Decreasing the number of hospitals, increasing the number of CHSs, and raising
      the proportion of health insurance compensation would effectively increase the
      transformation of potential medical demand. But currently, changes of the
      outpatient prices didn't play a role in the transformation of potential medical
      demand. CONCLUSIONS: Combined with validation analysis and model simulation, we
      suggest some possible solutions. The main factors causing potential medical
      demand are accessibility to medical services and proportion of health insurance
      compensation. Thus, adjusting the number of hospitals and CHSs and increasing the
      proportion of health insurance compensation should decrease the actual percentage
      of patients not seeking medical care and accelerate the transformation of
      potential medical demand, which deserved being concerned in policymaking.

PMID- 26297985
TI  - MiRNA-TF-gene network analysis through ranking of biomolecules for multi
      informative uterine leiomyoma dataset.
AB  - Gene ranking is an important problem in bioinformatics. Here, we propose a new
      framework for ranking biomolecules (viz., miRNAs, transcription-factors/TFs and
      genes) in a multi-informative uterine leiomyoma dataset having both gene
      expression and methylation data using (statistical) eigenvector centrality based
      approach. At first, genes that are both differentially expressed and methylated,
      are identified using Limma statistical test. A network, comprising these genes,
      corresponding TFs from TRANSFAC and ITFP databases, and targeter miRNAs from
      miRWalk database, is then built. The biomolecules are then ranked based on
      eigenvector centrality. Our proposed method provides better average accuracy in
      hub gene and non-hub gene classifications than other methods. Furthermore, pre
      ranked Gene set enrichment analysis is applied on the pathway database as well as
      GO-term databases of Molecular Signatures Database with providing a pre-ranked
      gene-list based on different centrality values for comparing among the ranking
      methods. Finally, top novel potential gene-markers for the uterine leiomyoma are
      provided. 

PMID- 26297986
TI  - Septin 9 Exhibits Polymorphic Binding to F-Actin and Inhibits Myosin and Cofilin
      Activity.
AB  - Septins are a highly conserved family of proteins in eukaryotes that is
      recognized as a novel component of the cytoskeleton. Septin 9 (SEPT9) interacts
      directly with actin filaments and functions as an actin stress fiber cross
      linking protein that promotes the maturation of nascent focal adhesions and cell
      migration. However, the molecular details of how SEPT9 interacts with F-actin
      remain unknown. Here, we use electron microscopy and image analysis to show that
      SEPT9 binds to F-actin in a highly polymorphic fashion. We demonstrate that the
      basic domain (B-domain) of the N-terminal tail of SEPT9 is responsible for actin
      cross-linking, while the GTP-binding domain (G-domain) does not bundle F-actin.
      We show that the B-domain of SEPT9 binds to three sites on F-actin, and the two
      of these sites overlap with the binding regions of myosin and cofilin. SEPT9
      inhibits actin-dependent ATPase activity of myosin and competes with the weakly
      bound state of myosin for binding to F-actin. At the same time, SEPT9
      significantly reduces the extent of F-actin depolymerization by cofilin. Taken
      together, these data suggest that SEPT9 protects actin filaments from
      depolymerization by cofilin and myosin and indicate a mechanism by which SEPT9
      could maintain the integrity of growing and contracting actin filaments. 

PMID- 26297987
TI  - NDRG1 overexpressing gliomas are characterized by reduced tumor vascularization
      and resistance to antiangiogenic treatment.
AB  - Hypoxia-regulated molecules play an important role in vascular resistance to
      antiangiogenic treatment. N-myc downstream-regulated-gene 1 (NDRG1) is
      significantly upregulated during hypoxia in glioma. It was the aim of the present
      study to analyze the role of NDRG1 on glioma angiogenesis and on antiangiogenic
      treatment. Orthotopically implanted NDRG1 glioma showed reduced tumor growth and
      vessel density compared to controls. RT-PCR gene array analysis revealed a 30
      fold TNFSF15 increase in NDRG1 tumors. Consequently, the supernatant from NDRG1
      transfected U87MG glioma cells resulted in reduced HUVEC proliferation, migration
      and angiogenic response in tube formation assays in vitro. This effect was
      provoked by increased TNFSF15 promoter activity in NDRG1 cells. Mutations in NF
      kappaB and AP-1 promoter response elements suppressed TNFSF15 promoter activity.
      Moreover, U87MG glioma NDRG1 knockdown supernatant contained multiple
      proangiogenic proteins and increased HUVEC spheroid sprouting. Sunitinib
      treatment of orhotopically implanted mice reduced tumor volume and vessel density
      in controls; in NDRG1 overexpressing cells no reduction of tumor volume or vessel
      density was observed. NDRG1 overexpression leads to reduced tumor growth and
      angiogenesis in experimental glioma via upregulation of TNFSF15. In NDRG1
      overexpressing glioma antiangiogenic treatment does not yield a therapeutic
      response.

PMID- 26297988
TI  - Androgen receptor inhibits epithelial-mesenchymal transition, migration, and
      invasion of PC-3 prostate cancer cells.
AB  - Bone metastasis is very common in prostate cancer (PCa) and causes severe pain.
      PC-3 is an androgen receptor (AR)-negative PCa cell line with high metastatic
      potential established from PCa bone metastasis. We observed that re-expression of
      AR, which is located in the cytoplasm in the absence of androgen, suppressed cell
      motility, migration, and invasion of PC-3 cells as determined by wound healing
      assay and transwell assay. Micro-Western Array and Western blotting analysis
      indicated that re-expression of AR increased APC, Akt2, Akt3, PI3K p85, phospho
      PI3K p85 Tyr458, PI3K p85, and E-cadherin but decreased GSK-3beta, phospho-GSK
      3beta Ser9, phospho-mTOR Ser2448, Skp2, NF-kappaB p50, Slug, N-cadherin, beta
      catenin, vimentin, MMP-9, and Snail. Migration and invasion of PC-3 and PC-3(AR)
      cells were promoted by EGF or IGF-1 but were suppressed by Casodex. Re-expression
      of AR reduced the activity of MMP-2 and MMP-9 in PC-3 cells. Our observations
      suggested that re-expressing AR suppresses migration and invasion of PC-3 cells
      via regulation of EMT marker proteins and MMP activity. 

PMID- 26297989
TI  - Chrysin attenuates liver fibrosis and hepatic stellate cell activation through
      TGF-beta/Smad signaling pathway.
AB  - We investigated the protective effect of chrysin on chronic liver fibrosis in
      mice and the potential mechanism underlying TGF-beta1-mediated hepatic stellate
      cells (HSCs) activation on fibrogenesis. Experimental fibrosis was established by
      intraperitoneal injection of mice with 20% v/v, 2 ml/kg CCl4 twice a week, for 7
      weeks. Mice were orally treated with 3 doses of chrysin (50, 100 and 200 mg/kg)
      or with vehicle as control. For the assessment of the spontaneous reversion of
      fibrosis, CCl4 treated animals were investigated after two weeks of recovery
      time. Silymarin was used as standard hepatoprotective flavonoid.
      Histopathological investigations showed that hepatic fibrosis grade was markedly
      reduced in the chrysin groups compared to the fibrotic one. Moreover, CCl4
      activated HSCs induced an upregulation of smooth muscle actin (alpha-SMA), an
      increased number of TGF-beta1 immunopositive cells and marked up-regulation of
      TGF-beta1. alpha-SMA and TGF-beta1 levels were significantly reduced in all
      chrysin treated groups in a dose-dependent manner, whereas the level of
      spontaneous reversal of fibrosis was lower compared to all flavonoid treated
      groups. Liver mRNA levels of Smad 2 in the 50, 100 and 200 mg/kg chrysin treated
      groups were significantly reduced by about 88.54%, 92.15% and 95.56% of the
      corresponding levels in the fibrosis mice group. The results were similar for
      mRNA levels of Smad 3. The protective response to silymarin was almost similar to
      that seen with the highest doses of chrysin. In this study, we have shown that
      chrysin has the efficacy to reverse CCl4-stimulated liver fibrosis by inhibition
      of HSCs activation and proliferation through TGF-beta1/Smad pathway. These
      results suggest that chrysin may be useful in stopping or reversing the
      progression of liver fibrosis and might offer the possibility to develop a new
      therapeutic drug, useful in treatment of chronic liver diseases. 

PMID- 26297990
TI  - Kinetics and molecular docking studies of cholinesterase inhibitors derived from
      water layer of Lycopodiella cernua (L.) Pic. Serm. (II).
AB  - Acetylcholinesterase (AChE) inhibitors increase the availability of acetylcholine
      in central cholinergic synapses and are the most promising drugs currently
      available for the treatment of Alzheimer's disease (AD). Our screening study
      indicated that the water fraction of the methanolic extract of Lycopodiella
      cernua (L.) Pic. Serm. significantly inhibited AChE in vitro. Bioassay-guided
      fractionation led to the isolation of a new lignan glycoside, lycocernuaside A
      (12), and fourteen known compounds (1-11 and 13-15). Compound 7 exhibited the
      most potent AChE inhibitory activity with an IC50 value of 0.23 MUM. Compound 15
      had the most potent inhibitory activity against BChE and BACE1 with IC50 values
      of 0.62 and 2.16 MUM, respectively. Compounds 4 and 7 showed mixed- and
      competitive-type AChE inhibition. Compound 7 noncompetitively inhibited BChE
      whereas 15 showed competitive and 8, 13, and 14 showed mixed-type inhibition. The
      docking results for complexes with AChE or BChE revealed that inhibitors 4, 7,
      and 15 stably positioned themselves in several pocket/catalytic domains of the
      AChE and BChE residues. 

PMID- 26297991
TI  - Xanthohumol inhibits cell cycle progression and proliferation of larynx cancer
      cells in vitro.
AB  - Xanthohumol (XN), a prenylflavonoid derived from the hop plant (Humulus lupulus
      L.) has been found to exhibit a broad spectrum of biological properties,
      including anti-cancer activity. In this study, the mechanisms involved in anti
      cancer activity of XN in human RK33 and RK45 larynx cancer cell lines were
      investigated. The effect of XN on the viability of larynx cancer and normal cells
      (human skin fibroblasts HSF and rat oligodendroglia-derived cells, OLN-93) was
      compared. Additionally, the influence of XN on proliferation, cell cycle
      progression, induction of apoptosis in larynx cancer cells, as well as the
      molecular mechanisms underlying in these processes were analyzed. XN promoted the
      reduction of cell viability in cancer cells, but showed low cytotoxicity to
      normal cells. The decrease in cell viability in the cancer cells was coupled with
      induction of apoptosis via two pathways. The mechanisms involved in these effects
      of XN were associated with cell growth inhibition by induction of cell cycle
      arrest in the G1 phase, increased p53 and p21/WAF1 expression levels,
      downregulation of cyclin D1 and Bcl-2, and activation of caspases-9, -8, and -3.
      Moreover, this compound inhibited phosphorylation of ERK1/2, suggesting a key
      role of the ERKs pathway in the XN-mediated growth suppressing effects against
      the studied cells. These results indicate that XN could be used as a potential
      agent for the treatment of patients with larynx cancer. 

PMID- 26297992
TI  - Growth factors mediated cell signalling in prostate cancer progression:
      Implications in discovery of anti-prostate cancer agents.
AB  - Cancer is one of the leading causes of mortality amongst world's population, in
      which prostate cancer is one of the most encountered malignancies among men.
      Globally, it is the sixth leading cause of cancer-related death in men. Prostate
      cancer is more prevalent in the developed world and is increasing at alarming
      rates in the developing countries. Prostate cancer is mostly a very sluggish
      progressing disease, caused by the overproduction of steroidal hormones like
      dihydrotestosterone or due to over-expression of enzymes such as 5-alpha
      reductase. Various studies have revealed that growth factors play a crucial role
      in the progression of prostate cancer as they act either by directly elevating
      the level of steroidal hormones or upregulating enzyme efficacy by the active
      feedback mechanism. Presently, treatment options for prostate cancer include
      radiotherapy, surgery and chemotherapy. If treatment is done with prevailing
      traditional chemotherapy; it leads to resistance and development of androgen
      independent prostate cancer that further complicates the situation with no cure
      option left. The current review article is an attempt to cover and establish an
      understanding of some major signalling pathways intervened through survival
      factors (IGF-1R), growth factors (TGF-alpha, EGF), Wnt, Hedgehog, interleukin,
      cytokinins and death factor receptor which are frequently dysregulated in
      prostate cancer. This will enable the researchers to design and develop better
      therapeutic strategies targeting growth factors and their cross talks mediated
      prostate cancer cell signalling. 

PMID- 26297993
TI  - Purification optimization for a recombinant single-chain variable fragment
      against type 1 insulin-like growth factor receptor (IGF-1R) by using design of
      experiment (DoE).
AB  - Design of experiment (DoE) is a statistics-based technique for experimental
      design that could overcome the shortcomings of traditional one-factor-at-a-time
      (OFAT) approach for protein purification optimization. In this study, a DoE
      approach was applied for optimizing purification of a recombinant single-chain
      variable fragment (scFv) against type 1 insulin-like growth factor receptor (IGF
      1R) expressed in Escherichia coli. In first capture step using Capto L, a 2-level
      fractional factorial analysis and successively a central composite circumscribed
      (CCC) design were used to identify the optimal elution conditions. Two main
      effects, pH and trehalose, were identified, and high recovery (above 95%) and low
      aggregates ratio (below 10%) were achieved at the pH range from 2.9 to 3.0 with
      32-35% (w/v) trehalose added. In the second step using cation exchange
      chromatography, an initial screening of media and elution pH and a following CCC
      design were performed, whereby the optimal selectivity of the scFv was obtained
      on Capto S at pH near 6.0, and the optimal conditions for fulfilling high DBC and
      purity were identified as pH range of 5.9-6.1 and loading conductivity range of 5
      12.5 mS/cm. Upon a further gel filtration, the final purified scFv with a purity
      of 98% was obtained. Finally, the optimized conditions were verified by a 20-fold
      scale-up experiment. The purities and yields of intermediate and final products
      all fell within the regions predicted by DoE approach, suggesting the robustness
      of the optimized conditions. We proposed that the DoE approach described here is
      also applicable in production of other recombinant antibody constructs.

PMID- 26297994
TI  - Combining a PagP fusion protein system with nickel ion-catalyzed cleavage to
      produce intrinsically disordered proteins in E. coli.
AB  - Many proteins contain intrinsically disordered regions that are highly solvent
      exposed and susceptible to post-translational modifications. Studying these
      protein segments is critical to understanding their physiologic regulation, but
      proteolytic degradation can make them difficult to express and purify. We have
      designed a new protein expression vector that fuses the target protein to the N
      terminus of the integral membrane protein, PagP. The two proteins are connected
      by a short linker containing the sequence SRHW, previously shown to be optimal
      for nickel ion-catalyzed cleavage. The methodology is demonstrated for an
      intrinsically disordered segment of cardiac troponin I. cTnI[135-209]-SRHW-PagP
      His6 fusion protein was overexpressed in Escherichia coli, accumulating in
      insoluble inclusion bodies. The protein was solubilized, purified using nickel
      affinity chromatography, and then cleaved with 0.5mM NiSO4 at pH 9.0 and 45 
      degrees C, all in 6M guanidine-HCl. Nickel ion-catalyzed peptide bond hydrolysis
      is an effective chemical cleavage technique under denaturing conditions that
      preclude the use of proteases. Moreover, nickel-catalyzed cleavage is more
      specific than the most commonly used agent, cyanogen bromide, which cleaves C
      terminal to methionine residues. We were able to produce 15 mg of purified
      cTnI[135-209] from 1L of M9 minimal media using this protocol. The methodology is
      more generally applicable to the production of intrinsically disordered protein
      segments.

PMID- 26297995
TI  - Full-length trimeric influenza virus hemagglutinin II membrane fusion protein and
      shorter constructs lacking the fusion peptide or transmembrane domain:
      Hyperthermostability of the full-length protein and the soluble ectodomain and
      fusion peptide make significant contributions to fusion of membrane vesicles.
AB  - Influenza virus is a class I enveloped virus which is initially endocytosed into
      a host respiratory epithelial cell. Subsequent reduction of the pH to the 5-6
      range triggers a structural change of the viral hemagglutinin II (HA2) protein,
      fusion of the viral and endosomal membranes, and release of the viral
      nucleocapsid into the cytoplasm. HA2 contains fusion peptide (FP), soluble
      ectodomain (SE), transmembrane (TM), and intraviral domains with respective
      lengths of ~ 25, ~ 160, ~ 25, and ~ 10 residues. The present work provides a
      straightforward protocol for producing and purifying mg quantities of full-length
      HA2 from expression in bacteria. Biophysical and structural comparisons are made
      between full-length HA2 and shorter constructs including SHA2 = SE, FHA2 = FP+SE,
      and SHA2-TM = SE+TM constructs. The constructs are helical in detergent at pH 7.4
      and the dominant trimer species. The proteins are highly thermostable in
      decylmaltoside detergent with Tm>90  degrees C for HA2 with stabilization
      provided by the SE, FP, and TM domains. The proteins are likely in a trimer-of
      hairpins structure, the final protein state during fusion. All constructs induce
      fusion of negatively-charged vesicles at pH 5.0 with much less fusion at pH 7.4.
      Attractive protein/vesicle electrostatics play a role in fusion, as the proteins
      are positively-charged at pH 5.0 and negatively-charged at pH 7.4 and the pH
      dependence of fusion is reversed for positively-charged vesicles. Comparison of
      fusion between constructs supports significant contributions to fusion from the
      SE and the FP with little effect from the TM.

PMID- 26297996
TI  - Tandem SUMO fusion vectors for improving soluble protein expression and
      purification.
AB  - Availability of highly purified proteins in quantity is crucial for detailed
      biochemical and structural investigations. Fusion tags are versatile tools to
      facilitate efficient protein purification and to improve soluble overexpression
      of proteins. Various purification and fusion tags have been widely used for
      overexpression in Escherichia coli. However, these tags might interfere with
      biological functions and/or structural investigations of the protein of interest.
      Therefore, an additional purification step to remove fusion tags by proteolytic
      digestion might be required. Here, we describe a set of new vectors in which
      yeast SUMO (SMT3) was used as the highly specific recognition sequence of
      ubiquitin-like protease 1, together with other commonly used solubility enhancing
      proteins, such as glutathione S-transferase, maltose binding protein, thioredoxin
      and trigger factor for optimizing soluble expression of protein of interest. This
      tandem SUMO (T-SUMO) fusion system was tested for soluble expression of the C
      terminal domain of TonB from different organisms and for the antiviral protein
      scytovirin. 

PMID- 26297997
TI  - Concomitant partial exon skipping by a unique missense mutation of RPS6KA3 causes
      Coffin-Lowry syndrome.
AB  - Coffin-Lowry syndrome (CLS) is an X-linked semi-dominant disorder characterized
      by diverse phenotypes including intellectual disability, facial and digital
      anomalies. Loss-of-function mutations in the Ribosomal Protein S6 Kinase
      Polypeptide 3 (RPS6KA3) gene have been shown to be responsible for CLS. Among the
      large number of mutations, however, no exonic mutation causing exon skipping has
      been described. Here, we report a male patient with CLS having a novel mutation
      at the 3' end of an exon at a splice donor junction. Interestingly, this
      nucleotide change causes both a novel missense mutation and partial exon skipping
      leading to a truncated transcript. These two transcripts were identified by cDNA
      sequencing of RT-PCR products. In the carrier mother, we found only wildtype
      transcripts suggesting skewed X-inactivation. Methylation studies confirmed X
      inactivation was skewed moderately, but not completely, which is consistent with
      her mild phenotype. Western blot showed that the mutant RSK2 protein in the
      patient is expressed at similar levels relative to his mother. Protein modeling
      demonstrated that the missense mutation is damaging and may alter binding to ATP
      molecules. This is the first report of exon skipping from an exonic mutation of
      RPS6KA3, demonstrating that a missense mutation and concomitant disruption of
      normal splicing contribute to the manifestation of CLS. 

PMID- 26297998
TI  - MicroRNA dynamics during human embryonic stem cell differentiation to pancreatic
      endoderm.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that have emerged as critical
      regulators of human embryonic stem cell (hESC) pluripotency and differentiation.
      Despite the wealth of information about the role individual that miRNAs play in
      these two processes, there has yet to be a large-scale temporal analysis of the
      dynamics of miRNA expression as hESCs move from pluripotency into defined
      lineages. In this report, we used Next Generation Sequencing (NGS) to map
      temporal expression of miRNAs over ten 24-hour intervals as pluripotent cells
      were differentiated into pancreatic endoderm. Of the 2042 known human miRNAs, 694
      had non-zero expression on all 11 days. Of these 694 miRNAs, 494 showed
      statistically significant changes in expression during differentiation. Clusters
      of miRNAs were identified, each displaying unique expression profiles distributed
      over multiple days. Selected miRNAs associated with pluripotency/differentiation
      (miR-302/367 and miR-371/372/373) and development/growth (miR-21, miR-25, miR
      103, miR-9, and miR-92a) were found to have distinct expression profiles
      correlated with changes in media used to drive the differentiation process. Taken
      together, the clustering of miRNAs to identify expression dynamics that occur
      over longer periods of time (days vs. hours) provides unique insight into
      specific stages of differentiation. Major shifts in defined stages of hESC
      differentiation appear to be heavily dependent upon changes in external
      environmental factors, rather than intrinsic conditions in the cells.

PMID- 26298000
TI  - Metabolic alteration--Overcoming therapy resistance in gastric cancer via PGK-1
      inhibition in a combined therapy with standard chemotherapeutics.
AB  - BACKGROUND AND OBJECTIVES: It can be assumed that PGK1 is involved in metastatic
      spread of gastric carcinomas. Furthermore PGK1 has a proven influence on the
      characteristics of tumor stem cells. The presence of malignant stem cells,
      regarding treatment resistance and recurrence, is of considerable importance. We
      hypothesized that inhibition of PGK1 makes these cells more sensitive to
      chemotherapeutic agents and therefore mediates an overcome of the existing
      therapy resistance. METHODS: All investigations were performed with human gastric
      adenocarcinoma cell lines. Small hairpin RNA knockdown of PGK1 via adenovirus
      shPGK1 was used for PGK1-inhibition. Chemotherapeutic agents were 5-FU and
      mitomycin. FACS, qRT-PCR, and xCELLigence were performed. RESULTS: Using the
      medium-sole-control indicating the highest cell viability and Triton indicating
      the lowest, mitomycin and 5-FU alone showed a significant decrease in cell
      viability. The treatment with AdvshPGK1 alone already showed a better decrease.
      The simultaneous application of chemotherapeutics and adenovirus showed the
      strongest effect and is comparable to the effect of Triton. CONCLUSIONS: We
      showed a significant decrease in cell viability after the simultaneous
      application of chemotherapeutics and adenovirus. These results suggest that PGK1
      inhibition is able to increase the vulnerability of gastric cancer cells and
      tumor stem cells to overcome the chemotherapeutic therapy resistance.

PMID- 26297999
TI  - Genetic variations of NKX2-5 in sporadic atrial septal defect and ventricular
      septal defect in Chinese Yunnan population.
AB  - Congenital heart disease (CHD) is the most common birth abnormality, and more
      than 40% CHD subtypes are sporadic atrial septal defect (ASD) and ventricular
      septal defect (VSD). The etiology of ASD and VSD remains largely unknown. NKX2-5
      gene is a highly conserved homeobox protein gene and expressed in the developing
      heart. Its mutations can cause sporadic ASD and VSD. This study aimed to
      investigate the genetic variations of NKX2-5 in ASD and VSD in Chinese Yunnan
      population. The whole 2 coding exon and partial flanking intron sequences of NKX2
      5 gene were screened using DNA sequencing in 107 ASD patients and 391 VSD
      patients as well as 487 healthy individuals (control) who had parental origin
      (three generations) from the Yunnan province in China. Results found that, 4
      reported single nucleotide polymorphisms (SNPs) (rs2277923, rs3729753, rs703752
      and rs202071628) were detected. A novel heterozygous DNA sequence variant (DSV)
      (1500G>C) in the 3'UTR region of NKX2-5 gene were identified in 2 VSD patients,
      but none in ASD and controls. One single nucleotide polymorphism (rs2277923), the
      frequency of which was significantly higher in ASD group, and the allele and
      genotype were associated with the occurrence of ASD. Besides, a weak statistical
      association existed between rs703752 and VSD (uncorrected P=0.028). The novel DSV
      (1500G>C) of NKX2-5 gene may contribute to a small number of VSD, and rs2277923
      SNP may contribute to the risk of sporadic ASD in Chinese Yunnan population. 

PMID- 26298001
TI  - Comparative clinicopathological changes in buffalo and cattle following infection
      by Pasteurella multocida B:2.
AB  - Haemorrhagic septicaemia (HS) is an acute, septicaemic disease of cattle and
      buffalo of Asia and Africa caused by Pasteurella multocida B:2 or E:2. Buffaloes
      are believed to be more susceptible than cattle. In this study, 9 buffaloes of 8
      months old were divided equally into 3 groups (Groups 1, 3, 5). Similarly, 9
      cattle of 8 months old were equally divided into 3 groups (Groups 2, 4, 6).
      Animals of Groups 1 and 2 were inoculated with PBS while Groups 3 and 4 were
      inoculated subcutaneously with 10(5) cfu/ml of P. multocida B:2. Animals of
      Groups 5 and 6 were inoculated intranasally with the same inoculum. Both
      buffaloes and cattle that were inoculated subcutaneously succumbed to the
      infection at 16 h and 18 h, respectively. Two buffaloes that were inoculated
      intranasally (Group 5) succumbed at 68 h while the remaining cattle and buffaloes
      survived the 72-h study period. Endotoxin was detected in the blood of infected
      cattle (Group 4) and buffaloes (Groups 3 and 5) prior to the detection of P.
      multocida B:2 in the blood. The endotoxin was detected in the blood of buffaloes
      of Group 3 and cattle of Group 4 at 0.5 h post-inoculation while buffaloes of
      Group 5 and cattle of Group 6 at 1.5 h. On the other hand, bacteraemia was
      detected at 2.5 h in buffaloes of Group 3 and cattle of Group 4 and at 12 h in
      buffaloes of Group 5 and cattle of Group 6. Affected cattle and buffaloes showed
      lesions typical of haemorrhagic septicaemia. These included congestion and
      haemorrhages in the organs of respiratory, gastrointestinal and urinary tracts
      with evidence of acute inflammatory reactions. The severity of gross and
      histopathology lesions in cattle and buffalo calves that succumbed to the
      infection showed insignificant (p > 0.05) difference. However, inoculated buffalo
      and cattle that survived the infection showed significantly (p < 0.05) less
      severe gross and histopathological changes than those that succumbed. In general,
      cattle are more resistant to intranasal infection by P. multocida B:2 than
      buffaloes.

PMID- 26298002
TI  - Combined effects of lactoferrin and lysozyme on Streptococcus pneumoniae killing.
AB  - Streptococcus pneumoniae is a common colonizer of the human nasopharynx, which
      can occasionally spread to sterile sites, causing diseases such as otitis media,
      sinusitis, pneumonia, meningitis and bacteremia. Human apolactoferrin (ALF) and
      lysozyme (LZ) are two important components of the mucosal innate immune system,
      exhibiting lytic effects against a wide range of microorganisms. Since they are
      found in similar niches of the host, it has been proposed that ALF and LZ could
      act synergistically in controlling bacterial spread throughout the mucosa. The
      combination of ALF and LZ has been shown to enhance killing of different
      pathogens in vitro, with ALF facilitating the latter action of LZ. The aim of the
      present work was to investigate the combined effects of ALF and LZ on S
      pneumoniae. Concomitant addition of ALF and LZ had a synergistic killing effect
      on one of the pneumococci tested. Furthermore, the combination of ALF and ALZ was
      more bactericidal than lysozyme alone in all pneumococcal strains. Pneumococcal
      surface protein A (PspA), an important vaccine candidate, partially protects
      pneumococci from ALF mediated killing, while antibodies against one PspA enhance
      killing of the homologous strain by ALF. However, the serological variability of
      this molecule could limit the effect of anti-PspA antibodies on different
      pneumococci. Therefore, we investigated the ability of anti-PspA antibodies to
      increase ALF-mediated killing of strains that express different PspAs, and found
      that antisera to the N-terminal region of PspA were able to increase pneumococcal
      lysis by ALF, independently of the sequence similarities between the molecule
      expressed on the bacterial surface and that used to produce the antibodies. LF
      binding to the pneumococcal surface was confirmed by flow cytometry, and found to
      be inhibited in presence of anti-PspA antibodies. On a whole, the results suggest
      a contribution of ALF and LZ to pneumococcal clearance, and confirm PspA's
      ability to interact with ALF.

PMID- 26298003
TI  - The ethanol metabolite acetaldehyde induces water and salt intake via two
      distinct pathways in the central nervous system of rats.
AB  - The sensation of thirst experienced after heavy alcohol drinking is widely
      regarded as a consequence of ethanol (EtOH)-induced diuresis, but EtOH in high
      doses actually induces anti-diuresis. The present study was designed to
      investigate the introduction mechanism of water and salt intake after heavy
      alcohol drinking, focusing on action of acetaldehyde, a metabolite of EtOH and a
      toxic substance, using rats. The aldehyde dehydrogenase (ALDH) inhibitor
      cyanamide was used to mimic the effect of prolonged acetaldehyde exposure because
      acetaldehyde is quickly degraded by ALDH. Systemic administration of a high-dose
      of EtOH at 2.5 g/kg induced water and salt intake with anti-diuresis. Cyanamide
      enhanced the fluid intake following EtOH and acetaldehyde administration.
      Systemic administration of acetaldehyde with cyanamide suppressed blood pressure
      and increased plasma renin activity. Blockade of central angiotensin receptor
      AT1R suppressed the acetaldehyde-induced fluid intake and c-Fos expression in the
      circumventricular organs (CVOs), which form part of dipsogenic mechanism in the
      brain. In addition, central administration of acetaldehyde together with
      cyanamide selectively induced water but not salt intake without changes in blood
      pressure. In electrophysiological recordings from slice preparations,
      acetaldehyde specifically excited angiotensin-sensitive neurons in the CVO. These
      results suggest that acetaldehyde evokes the thirst sensation following heavy
      alcohol drinking, by two distinct and previously unsuspected mechanisms,
      independent of diuresis. First acetaldehyde indirectly activates AT1R in the
      dipsogenic centers via the peripheral renin-angiotensin system following the
      depressor response and induces both water and salt intake. Secondly acetaldehyde
      directly activates neurons in the dipsogenic centers and induces only water
      intake. 

PMID- 26298004
TI  - Detection of the BLV provirus from nasal secretion and saliva samples using BLV
      CoCoMo-qPCR-2: Comparison with blood samples from the same cattle.
AB  - Bovine leukemia virus (BLV) induces enzootic bovine leukosis, which is the most
      common neoplastic disease in cattle. Sero-epidemiological studies show that BLV
      infection occurs worldwide. Direct contact between infected and uninfected cattle
      is thought to be one of the risk factors for BLV transmission. Contact
      transmission occurs via a mixture of natural sources, blood, and exudates. To
      confirm that BLV provirus is detectable in these samples, matched blood, nasal
      secretion, and saliva samples were collected from 50 cattle, and genomic DNA was
      extracted. BLV-CoCoMo-qPCR-2, an assay developed for the highly sensitive
      detection of BLV, was then used to measure the proviral load in blood (n=50),
      nasal secretions (n=48), and saliva (n=47) samples. The results showed that 35
      blood samples, 14 nasal secretion samples, and 6 saliva samples were positive for
      the BLV provirus. Matched blood samples from cattle that were positive for the
      BLV provirus (either in nasal secretion or saliva samples) were also positive in
      their blood. The proviral load in the positive blood samples was >14,000
      (copies/1*10(5) cells). Thus, even though the proviral load in the nasal
      secretion and saliva samples was much lower (<380 copies/1*10(5) cells) than that
      in the peripheral blood, prolonged direct contact between infected and healthy
      cattle may be considered as a risk factor for BLV transmission. 

PMID- 26298005
TI  - Anti-inflammatory effects of methylthiouracil in vitro and in vivo.
AB  - The screening of bioactive compound libraries can be an effective approach for
      repositioning FDA-approved drugs or discovering new treatments for human
      diseases. Here, methylthiouracil (MTU), an antithyroid drug, was examined for its
      effects on lipopolysaccharide (LPS)-mediated vascular inflammatory responses. The
      anti-inflammatory activities of MTU were determined by measuring permeability,
      human neutrophil adhesion and migration, and activation of pro-inflammatory
      proteins in LPS-activated human umbilical vein endothelial cells and mice. We
      found that post-treatment with MTU inhibited LPS-induced barrier disruption,
      expression of cell adhesion molecules (CAMs), and adhesion/transendothelial
      migration of human neutrophils to human endothelial cells. MTU induced potent
      inhibition of LPS-induced endothelial cell protein C receptor (EPCR) shedding. It
      also suppressed LPS-induced hyperpermeability and neutrophil migration in vivo.
      Furthermore, MTU suppressed the production of tumor necrosis factor-alpha (TNF
      alpha) and interleukin (IL)-6, and the activation of nuclear factor-kappaB (NF
      kappaB) and extracellular regulated kinases (ERK) 1/2 by LPS. Moreover, post
      treatment with MTU resulted in reduced LPS-induced lethal endotoxemia. These
      results suggest that MTU exerts anti-inflammatory effects by inhibiting
      hyperpermeability, expression of CAMs, and adhesion and migration of leukocytes,
      thereby endorsing its usefulness as a therapy for vascular inflammatory diseases.

PMID- 26298007
TI  - Decreasing the toxicity of paraquat through the complexation with sodium
      salicylate: Stoichiometric analysis.
AB  - Over the last decades, paraquat (1,1'-dimethyl-4,4'-bipyridilium dichloride; PQ)
      has been involved in numerous fatalities especially attributed to suicide
      attempts. Previously, it was shown that salicylates, namely sodium salicylate
      (NaSAL) and lysine acetylsalicylate (LAS) may form complexes with PQ, which may
      contribute to prevent its toxicity. The direct chemical reactivity between PQ and
      NaSAL was previously studied by liquid chromatography/electrospray
      ionization/mass spectrometry/mass spectrometry, showing the formation of
      complexes, though reported data was not fully conclusive. In the present study,
      the structure of the complex of PQ with NaSAL is fully characterized by
      crystallography. It was observed that PQ is complexed with 4 NaSAL molecules.
      Since formulations containing PQ and salicylates have been proposed, these
      results point that the stoichiometry of 1:4 (PQ:salicylates) should be considered
      to optimize prevention of PQ-mediated toxic effects. 

PMID- 26298006
TI  - Identification of protein expression alterations in gefitinib-resistant human
      lung adenocarcinoma: PCNT and mPR play key roles in the development of gefitinib
      associated resistance.
AB  - Gefitinib is the first-line chemotherapeutic drug for treating non-small cell
      lung cancer (NSCLC), which comprises nearly 85% of all lung cancer cases
      worldwide. However, most patients eventually develop drug resistance after 12-18
      months of treatment. Hence, investigating the drug resistance mechanism and
      resistance-associated biomarkers is necessary. Two lung adenocarcinoma cell
      lines, PC9 and gefitinib-resistant PC9/Gef, were established for examining
      resistance mechanisms and identifying potential therapeutic targets. Two
      dimensional differential gel electrophoresis and matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry were used for examining global
      protein expression changes between PC9 and PC9/Gef. The results revealed that 164
      identified proteins were associated with the formation of gefitinib resistance in
      PC9 cells. Additional studies using RNA interference showed that progesterone
      receptor membrane component 1 and pericentrin proteins have major roles in
      gefitinib resistance. In conclusion, the proteomic approach enabled identifying
      of numerous proteins involved in gefitinib resistance. The results provide useful
      diagnostic markers and therapeutic candidates for treating gefitinib-resistant
      NSCLC.

PMID- 26298008
TI  - The Arabidopsis RING Domain Protein BOI Inhibits Flowering via CO-dependent and
      CO-independent Mechanisms.
AB  - BOTRYTIS SUSCEPTIBLE1 INTERACTOR (BOI) and its three homologs (BOIs) are RING
      domain-containing proteins that repress flowering. Here, we investigated how BOIs
      repress flowering. Genetic analysis of the boiQ quadruple mutant indicates that
      BOIs repress flowering mainly through FLOWERING LOCUS T (FT). BOIs repress the
      expression of FT by CONSTANS (CO)-dependent and -independent mechanisms: in the
      CO-dependent mechanism, BOIs bind to CO, inhibit the targeting of CO to the FT
      locus, and thus repress the expression of FT; in the CO-independent mechanism,
      BOIs target the FT locus via a mechanism that requires DELLAs but not CO. This
      dual repression of FT makes BOIs strong repressors of flowering in both CO
      dependent and CO-independent pathways in Arabidopsis thaliana. Our finding that
      BOIs inhibit CO targeting further suggests that, in addition to modulating CO
      mRNA expression and CO protein stability, flowering regulation can also modulate
      the targeting of CO to FT.

PMID- 26298009
TI  - The role of food experiences during early childhood in food pleasure learning.
AB  - Infants are born equipped to ingest nutrients, but have to learn what to eat.
      This must occur early, because the mode of feeding evolves dramatically, from
      "tube" feeding in utero to eating family foods. Eating habits established during
      early years contribute to the development of subsequent eating habits. Therefore,
      it is fundamental to understand the most important early periods (between birth
      and 2 years, i.e. onset of food neophobia) for the development of eating habits
      and the drivers of this development. The role of pleasure in eating is central,
      especially during childhood when cognitive drivers of food choices may be less
      prominent than later in life. It is not easy to define and measure pleasure of
      eating in early childhood. However, it is possible to identify the
      characteristics of the eating experience which contribute to drive infant's
      eating and to shape preferences (food sensory properties; food rewarding
      properties; social context of eating). The learning processes involve repeated
      exposure (including to a variety of flavours), association with post-absorptive
      consequences and with contextual signals (including family members). The
      important early periods for learning food pleasure start being well identified.
      Beyond the first flavour discoveries during the prenatal and lactation periods
      (through the infant's exposure to flavours from foods of the mother's diet), the
      most important phase may be the beginning of complementary feeding. Infants
      discover the sensory (texture, taste and flavour) and nutritional properties
      (energy density) of the foods that will ultimately compose their adult diet;
      parents are still in charge of providing appropriate foods, timing, context for
      eating. Inter-individual differences in food pleasure learning, related to
      temperamental dimensions, or to sensory sensitivity also have to be taken into
      account.

PMID- 26298011
TI  - Treg-Mediated Immune Tolerance and the Risk of Solid Cancers: Findings From EPIC
      Heidelberg.
AB  - BACKGROUND: Laboratory-based, mechanistic, and prognosis studies suggest that a
      shift from antitumor immunity towards tumor-immune tolerance plays a major role
      in carcinogenesis. However, prospective epidemiological studies on the
      consequences of differing immune tolerance levels prior to clinical manifestation
      are missing. METHODS: A case-cohort study embedded in EPIC-Heidelberg was
      conducted comprising incident cases of breast (n = 399), colorectal (n = 185),
      lung (n = 149), and prostate (n = 378) cancer, which occurred during 6.6 years of
      follow-up, and a subcohort (n = 807). Foxp3+ regulatory T-lymphocytes and CD3+ T
      lymphocytes were measured by quantitative polymerase chain reaction-based DNA
      methylation analysis in prediagnostic leukocyte samples. Hazard ratios (HRs) for
      associations of cancer risk with the ratio of both parameters, the "cellular
      ratio of immune tolerance" (ImmunoCRIT), were estimated using Cox regression
      models. All statistical tests were two-sided. RESULTS: ImmunoCRIT values were
      positively associated with the risk of lung (highest vs lowest tertile, HR =
      1.98, 95% confidence interval = 1.06 to 3.69, P trend = .0263) and colorectal
      cancer (HR = 1.59, 95% CI = 0.99 to 2.54, P trend = .0069) after multivariable
      adjustment, but not with prostate cancer risk. Regarding breast cancer
      significant heterogeneity by estrogen receptor (ER) status was observed (P
      heterogeneity = .02), and the ImmunoCRIT was associated with the risk of ER
      negative breast cancer (HR = 3.34, 95% CI = 1.52 to 7.35, P trend <= .001), but
      not ER-positive breast cancer. CONCLUSION: The present study indicates that
      increased peripheral immune tolerance may be an independent risk factor for lung,
      colorectal, and ER-negative breast cancer, whereas its role on the development of
      prostate and ER-positive breast tumors remains uncertain.

PMID- 26298010
TI  - Increased Circulating Visfatin Is Associated With Progression of Kidney Disease
      in Non-Diabetic Hypertensive Patients.
AB  - BACKGROUD: Declining renal function is an independent risk factor for all-cause
      mortality in cardiovascular disease. Visfatin has been described as a marker of
      inflammation and endothelial dysfunction, but whether circulating visfatin levels
      are predictive to a subsequent decline in renal function remains unclear.
      METHODS: In total, 200 nondiabetic, non-proteinuric hypertensive outpatients with
      initial serum creatinine (Scr) <=1.5 mg/dl were enrolled. Plasma visfatin
      concentration and endothelial function estimated by brachial artery flow-mediated
      dilatation (FMD) were determined in the study subjects. The primary endpoints
      were the occurrence of renal events including doubling of Scr, 25% loss of
      glomerular filtration rate (GFR) from baseline values, and the occurrence of end
      stage renal disease during follow-up. RESULTS: The mean annual rate of GFR
      decline (DeltaGFR/y) was -1.26+/-2.76 ml/min/1.73 m(2) per year during follow-up
      (8.6+/-2.5 years). At baseline, plasma visfatin was negatively correlated with
      estimated GFR. In longitudinal analysis, the DeltaGFR/y was correlated with
      visfatin, baseline GFR, FMD, systolic blood pressure, and fasting blood glucose
      (FBG). Multivariate analysis indicated that increased visfatin (r = -0.331, P
      <0.001), baseline GFR (r = -0.234, P = 0.001), FMD (r = 0.163, P = 0.015), and
      FBG (r = -0.160, P = 0.015) are independent predictors of DeltaeGFR/y. Cox
      regression model analysis showed that visfatin (hazard ratio (HR), 1.09; 95%
      confidence interval (CI), 1.05-1.13, P <0.001), FBG (HR, 1.01; 95% CI, 1.00-1.02,
      P = 0.020), and FMD (HR, 0.87; 95% CI, 0.76-1.00, P = 0.049) were independently
      associated with the risk of developing future renal events. CONCLUSIONS:
      Increased circulating visfatin are associated with subsequent decline in renal
      function in nondiabetic hypertensive patients.

PMID- 26298012
TI  - A Meckel's diverticulum presenting as pyogenic liver abscesses.
AB  - Meckel's diverticula are the most common congenital malformation of the small
      intestine. The condition is rarely symptomatic and is usually an incidental
      finding during surgery. Bleeding in children and obstruction in adults are the
      most common symptomatic presentations. Our case involves a 50-year-old man with
      multiple pyogenic liver abscesses due to a Meckel's diverticulum. The abscesses
      were percutaneously drained and the diverticulum was eventually resected.
      Pyogenic liver abscess is a very rare presentation of a Meckel's diverticulum.
      The diverticulum in our case appeared to have a thickened wall on imaging but no
      signs of acute inflammation were present on the CT scan or noticed
      intraoperatively. It was presumed to be the possible source as all other
      possibilities were ruled out. Ultimately, the surgical pathology revealed acute
      inflammation and focal abscess. We propose that elective resection of a Meckel's
      diverticulum should be considered in the setting of pyogenic liver abscess with
      no other identifiable source. 

PMID- 26298013
TI  - Annual dynamics of North Sea bacterioplankton: seasonal variability superimposes
      short-term variation.
AB  - The dynamics of coastal marine microbial communities are driven by seasonally
      changing abiotic and biotic factors as well as by rapidly occurring short-term
      changes such as river fresh water influxes or phytoplankton blooms. We examined
      the variability of the free-living bacterioplankton at Helgoland Roads (German
      Bight, North Sea) over a period of one year with high temporal and taxonomic
      resolution to reveal variation patterns and main influencing factors. 16S rRNA
      gene tag sequencing of the bacterioplankton community hints at annual recurrence
      and resilience of few main taxa belonging to Alphaproteobacteria,
      Betaproteobacteria, Flavobacteriia, Acidimicrobiia and Thermoplasmata. Multiple
      regression analyses with various environmental factors revealed changes in water
      current patterns and resulting phytoplankton blooms as the main driving factors
      for short-term variation and temperature as the overlying factor for seasonal
      variation. Comparison of bacterioplankton successions during spring and summer
      phytoplankton blooms revealed the same dominating Flavobacteriia operational
      taxonomic units (OTUs) but shifts in Roseobacter related OTUs
      (Alphaproteobacteria) and SAR92 clade members (Gammaproteobacteria). Network
      analysis suggests that during spring and summer phytoplankton blooms temperature
      dependent guilds are formed. In conclusion, our data imply that short-term
      bacterioplankton successions in response to phytoplankton blooms are indirectly
      affected by temperature, which is a major niche-defining factor in the German
      Bight. 

PMID- 26298014
TI  - The activated sludge bulking filament Eikelboom morphotype 0803 embraces more
      than one member of the Chloroflexi.
AB  - The Eikelboom filamentous morphotype 0803 is commonly found in activated sludge
      systems globally, where it contributes to sludge bulking events. Earlier reports
      have suggested that it is a member of both the Proteobacteria and Chloroflexi.
      This study shows that this filament contributing to a period of poor sludge
      settleability in an Australian activated sludge plant is a member of the
      Chloroflexi, but not within the Caldilinea, as reported for this morphotype in
      Danish plants. Instead, it is a member of the Anaerolineae. The fluorescent
      signals generated in these filaments using the FISH probes designed here were
      unevenly distributed, a situation similar to that seen earlier in the
      Anaerolineae morphotype 0092 to which it is more closely related phylogenetically
      than it is to the Caldilinea morphotype 0803. FISH-based surveys showed that this
      0803 phylotype is uncommon in Australian activated sludge systems, and where seen
      is present usually at low abundances. The FISH probes described here will
      facilitate attempts to map the distribution and impact of this Australian
      filament morphotype 0803 in activated sludge systems of different configurations
      in plants around the world. 

PMID- 26298015
TI  - Molecular phylogeny and diversity of Fusarium endophytes isolated from tomato
      stems.
AB  - Plant tissues are a known habitat for two types of Fusarium species: plant
      pathogens and endophytes. Here, we investigated the molecular phylogeny and
      diversity of endophytic fusaria, because endophytes are not as well studied as
      pathogens. A total of 543 Fusarium isolates were obtained from the inside of
      tomato stems cultivated in soils mainly obtained from agricultural fields. We
      then determined partial nucleotide sequences of the translation elongation factor
      1 alpha (EF-1alpha) genes of the isolates. Among the isolates from tomato, 24 EF
      1alpha gene sequence types (EFST) were found: nine were classified as being from
      the Fusarium oxysporum species complex and its sister taxa (FOSC, 332 isolates),
      seven from the F. fujikuroi species complex (FFSC, 75 isolates) and eight from
      the F. solani species complex (FSSC, 136 isolates). To determine more
      characteristic details of the tomato isolates, we isolated 180 fusaria directly
      from soils and found 95% of them were nested within the FOSC (82 isolates; five
      EFSTs), FFSC (21 isolates; six FESTs) and FSSC (68 isolates; 11 EFSTs). These
      results suggested that the dominant Fusarium endophytes within tomato stems were
      members of the same three species complexes, which were also the dominant fusaria
      in the soils. 

PMID- 26298016
TI  - Characterization of sophorolipid biosynthetic enzymes from Starmerella bombicola.
AB  - Altering glycolipid structure by genetic engineering of Starmerella bombicola is
      a recently started research topic and worthy alternative to the unsuccessful
      selective feeding strategies conventionally applied to reach this goal. One
      question to be addressed when expressing heterologous proteins in S. bombicola is
      the activity of the subsequent biosynthetic enzymes toward such modified
      substrates. In this scope, we studied the substrate specificity of the UDP
      glucosyltransferases UgtA1 and UgtB1, responsible for the stepwise synthesis of
      sophorolipids from a hydroxylated fatty acid, and that of the acetyltransferase,
      responsible for acetylation of the sophorolipid molecule. All enzymes showed
      specificity toward a C18:1 chained acceptor and both glucosyltransferases were
      highly selective toward the UDP-glucose donor. Severe product inhibition of the
      glucosyltransferases explains the limited accumulation of sophorolipid
      intermediates by earlier created single deletion mutants of S. bombicola.
      Finally, a more detailed study of the acetylation of sophorolipid intermediates
      sheds light on the enzymatic cascade during synthesis. 

PMID- 26298017
TI  - Identification and characterization of lipases from Malassezia restricta, a
      causative agent of dandruff.
AB  - Dandruff, a skin disorder affecting 50% of the world population, is linked with
      proliferation of lipophilic yeasts of the genus Malassezia (particularly
      Malassezia globosa and M. restricta). Most Malassezia species show a unique lipid
      dependency and require external lipids for growth. Genome mining of the
      incomplete M. restricta genome led to the identification of eight lipase
      sequences. Sequences representing the class 3 and LIP lipase families were used
      to clone the lipases MrLip1, MrLip2 and MrLip3, recombinantly expressed in Pichia
      pastoris, and tested for their activity using mono-, di- and triacylglycerol
      substrates. Hydrolysis by the M. restricta lipase MrLip1 and MrLip2 (family class
      3) was limited to the mono- and diacylglycerol, while MrLip3 (family LIP)
      hydrolyzed all three substrates. This result confirms that Malassezia family LIP
      lipases are responsible for the hydrolysis of triacylglycerols, the main
      component of human sebum. Furthermore, the information regarding lipases from M.
      restricta presented here might aid in the search for anti-dandruff agents. 

PMID- 26298018
TI  - Polymicrobial Candida biofilms: friends and foe in the oral cavity.
AB  - The role of polymicrobial biofilm infections in medicine is becoming more
      apparent. Increasing number of microbiome studies and deep sequencing has enabled
      us to develop a greater understanding of how positive and negative microbial
      interactions influence disease outcomes. An environment where this is
      particularly pertinent is within the oral cavity, a rich and diverse ecosystem
      inhabited by both bacteria and yeasts, which collectively occupy and coexist
      within various niches as biofilm communities. Studies within this environment
      have however tended to be subject to extensive independent investigation, in the
      context of either polymicrobial bacterial communities or yeast biofilms, but
      rarely both together. It is clear however that they are not mutually exclusive.
      Therefore, this review aims to explore the influence of candidal populations on
      the composition of these complex aggregates and biofilm communities, to
      investigate their mechanistic interactions to understand how these impact
      clinical outcomes, and determine whether we can translate how this knowledge can
      be used to improve patient management. 

PMID- 26298020
TI  - The effect of ankle brace type on braking response time-A randomised study.
AB  - INTRODUCTION: The question whether or not a patient with an ankle brace should
      drive a car is of obvious importance because brake response time (BRT) is
      considered one of the most important factors for driving safety. MATERIALS AND
      METHODS: Applying a crossover study design, 70 healthy participants (35 women, 35
      men) participated in our study. BRT was assessed using a custom-made driving
      simulator. We assessed BRT under six conditions: without a brace (control) (1),
      with a typical postoperative ankle brace with adjustable ROM and the settings:
      unrestricted (2), fixed at 15 degrees  (3) plantar flexion, restricted with 15
      degrees /50 degrees  (4) (dorsal/plantar flexion), a brace for ligament
      instabilities (5) and an elastic ankle bandage (6). Participants were instructed
      to apply the brake pedal exclusively with the right foot as quickly as possible
      on receipt of a visual stimulus. RESULTS: The 70 participants showed
      significantly impaired BRT with the ankle brace for ROM restriction in the
      settings: unrestricted (p<0.001), fixed at 15 degrees  plantar flexion (p<0.001)
      and 15 degrees /50 degrees  dorsal/plantar flexion (p<0.001) as compared to the
      control group. BRT was not impaired with the brace for ankle instabilities or the
      elastic ankle bandage. CONCLUSIONS: In conclusion, right-sided ROM restricting
      ankle braces involve significant impairment of BRT in healthy participants. No
      such prolonged BRT was found for an elastic ankle bandage or the ligament brace.

PMID- 26298019
TI  - Surgical lung cancer patients' views about smoking and support to quit after
      diagnosis: a qualitative study.
AB  - PURPOSE: Evidence suggests that quitting smoking improves symptoms as well as
      disease-related mortality for cancer patients. However, smoking cessation support
      is typically not well integrated into routine cancer care even in the case of
      lung cancer.. We explored surgical lung cancer patients' views about smoking and
      about their preferences for support to help them to quit. METHODS: We conducted
      semi-structured, qualitative interviews with 22 surgical lung cancer patients
      with a smoking history, after treatment with surgery. Data were analysed using
      the framework approach. RESULTS: Although diagnosis promoted a successful quit
      attempt in some, others continued smoking or relapsed after a quit attempt. Most
      participants wished they were a non-smoker but, in conflict with this, also felt
      that smoking was enjoyable, helped with psychological coping or had some health
      benefits. Some also demonstrated a fatalist attitude towards the potential
      detrimental health effects. However, all participants felt that it was important
      for health professionals to address smoking and some wanted cessation support
      although it was often not provided. Participants wanted support to start as early
      as possible and to continue for the first weeks after discharge. CONCLUSIONS:
      Surgical lung cancer patients often stop smoking during hospitalisation, and many
      want to remain quit but relapse shortly after discharge. Although it is often not
      provided, many patients want to be offered support to help them quit.
      IMPLICATIONS FOR CANCER SURVIVORS: Surveys suggest that clinicians believe that
      addressing smoking will be difficult and/or unwanted. However, these findings
      suggest that surgical lung cancer patients would tolerate, and most would prefer,
      integration of smoking cessation support into routine cancer care.

PMID- 26298021
TI  - Neuroprotective effects of Ganoderma lucidum polysaccharides against traumatic
      spinal cord injury in rats.
AB  - INTRODUCTION: Ganoderma lucidum (G. lucidum) is a mushroom belonging to the
      polyporaceae family of Basidiomycota and has widely been used as a traditional
      medicine for thousands of years. G. lucidum has never been studied in traumatic
      spinal cord injury. The aim of this study is to investigate whether G. lucidum
      polysaccharides (GLPS) can protect the spinal cord after experimental spinal cord
      injury. MATERIALS AND METHODS: Rats were randomized into five groups of eight
      animals each: control, sham, trauma, GLPS, and methylprednisolone. In the control
      group, no surgical intervention was performed. In the sham group, only a
      laminectomy was performed. In all the other groups, the spinal cord trauma model
      was created by the occlusion of the spinal cord with an aneurysm clip. In the
      spinal cord tissue, caspase-3 activity, tumour necrosis factor-alpha levels,
      myeloperoxidase activity, malondialdehyde levels, nitric oxide levels, and
      superoxide dismutase levels were analysed. Histopathological and ultrastructural
      evaluations were also performed. Neurological evaluation was performed using the
      Basso, Beattie, and Bresnahan locomotor scale and the inclined-plane test.
      RESULTS: After traumatic spinal cord injury, increases in caspase-3 activity,
      tumour necrosis factor-alpha levels, myeloperoxidase activity, malondialdehyde
      levels, and nitric oxide levels were detected. After the administration of GLPS,
      decreases were observed in tissue caspase-3 activity, tumour necrosis factor
      alpha levels, myeloperoxidase activity, malondialdehyde levels, and nitric oxide
      levels. Furthermore, GLPS treatment showed improved results in histopathological
      scores, ultrastructural scores, and functional tests. CONCLUSIONS: Biochemical,
      histopathological, and ultrastructural analyses and functional tests reveal that
      GLPS exhibits meaningful neuroprotective effects against spinal cord injury.

PMID- 26298022
TI  - Common complications in hip fracture surgery: Tips/tricks and solutions to avoid
      them.
AB  - Surgical management of hip fractures in elderly people is challenging and
      complications relating to surgery could be devastating. They often lead to
      reoperation and revision surgery and can be associated with significantly
      increased morbidity and mortality. The most common surgical complications after
      internal fixation of hip fractures include cut-out, nonunion, Z-effect/medial
      migration, periimplant failure and avascular necrosis. High quality surgical
      fixation is of outmost importance to avoid surgical complications. This article
      presents the aetiology, risk factors and incidence of perioperative and post
      fracture fixation complications. Technical tips and tricks for a successful
      fixation as well as the contemporary evidence surrounding the augmentation of
      osteoporotic bone fixation in internal fixation of hip fractures are discussed. 

PMID- 26298023
TI  - Complications and patient-reported outcome after hip fracture. A consecutive
      annual cohort study of 664 patients.
AB  - INTRODUCTION: The aim of every patient with hip fracture is to regain previous
      function but we know little about the outcome, especially patient-reported
      outcome. We wanted to investigate what factors influence the result one year
      after hip fracture, including fast-track for hip fracture patients, as well as
      investigating the patients' satisfaction with their rehabilitation and to what
      degree they regained their pre-fracture function. METHODS: All patients (>20
      years, non-pathological fracture, residents in the catchment area, n=664) having
      surgery for hip fracture at our hospital during 2011 were included in a
      retrospective cohort study. From medical records, information was gathered about
      pre-fracture condition as well as fracture type, surgical details, length of stay
      and whether the patient entered the hospital through the fast-track system.
      Medical records were scrutinised for general complications up to six months and
      for local complications up to one year after surgery. A postal questionnaire was
      sent one year after surgery inquiring about health status, pain and satisfaction
      along with multiple-choice questions regarding mobility and rehabilitation.
      Variables were analysed with linear regression or the proportional odds model.
      RESULTS: The most common general complications were new falls, pneumonia and new
      fractures. Deep infection was the most frequent local complication. The only
      significant effect of the fast-track system was shorter time to surgery (78 vs.
      62% had surgery within 24h, p<0.001). A total of 29% reported to have regained
      their previous mobility and 30% considered the rehabilitation to be adequate.
      Mean value for pain VAS was 24 (SD 22) and for satisfaction 28 (SD 25). Absence
      of general and local complications correlated to satisfaction and hip pain.
      General complications correlated to loss of function. Higher age correlated to
      inadequate rehabilitation. CONCLUSION: General complications seem to be the major
      risk factor, being the only factor affecting functional outcome and together with
      local complications affecting pain and satisfaction. To avoid general
      complications, co-operation between orthopaedic surgeons and internists may be
      crucial in the aftercare of hip fracture patients. A majority did not receive
      adequate rehabilitation and efforts need to be made to improve the rehabilitation
      process.

PMID- 26298024
TI  - Physical activity in COPD patients decreases short-acting bronchodilator use and
      the number of exacerbations.
AB  - BACKGROUND: Physically inactive patients with chronic obstructive pulmonary
      disease (COPD) exhibit higher rates of exacerbations and symptoms of dyspnoea
      than active patients. Whether the use of COPD medication explains these
      differences is not known. AIM: This study evaluated differences in the use of
      COPD medication and the number of exacerbations due to physical activity.
      METHODS: A COPD cohort (N = 719) was followed through medical records to identify
      hospital admissions, and exercise activity was evaluated using mailed
      questionnaires. The national drug reimbursement registry identified drug
      purchases for one year. RESULTS: The use of maintenance therapies, such as long
      acting muscarinic antagonists (LAMAs), long-acting beta agonists (LABAs), inhaled
      corticosteroids (ICS), and theophylline, did not differ significantly between
      physically active (N = 346) and inactive (N = 355) COPD patients. The cumulative
      dose of salbutamol (85 vs. 218 mg, adjusted P = 0.01) and oral corticosteroids
      (OCS) (621 vs. 1068 mg, adjusted P = 0.02) were significantly higher in inactive
      patients, regardless of disease severity. LABAs, LAMAs, and ICS were used in
      reduced doses in both patient groups compared to daily defined doses (DDD).
      Physical activity was independently associated with the number of hospital
      admissions and the use of OCS and short-acting bronchodilators. CONCLUSION:
      Physical inactivity in COPD was not associated with poorer use of maintenance
      therapies. In contrast, inactivity was independently associated with the number
      of exacerbations measured by hospital admissions and the use of OCS and short
      acting symptom-relieving medications.

PMID- 26298025
TI  - Transplantation dose alters the dynamics of human neural stem cell engraftment,
      proliferation and migration after spinal cord injury.
AB  - The effect of transplantation dose on the spatiotemporal dynamics of human neural
      stem cell (hNSC) engraftment has not been quantitatively evaluated in the central
      nervous system. We investigated changes over time in engraftment/survival,
      proliferation, and migration of multipotent human central nervous system-derived
      neural stem cells (hCNS-SCns) transplanted at doses ranging from 10,000 to
      500,000 cells in spinal cord injured immunodeficient mice. Transplant dose was
      inversely correlated with measures of donor cell proliferation at 2 weeks post
      transplant (WPT) and dose-normalized engraftment at 16 WPT. Critically, mice
      receiving the highest cell dose exhibited an engraftment plateau, in which the
      total number of engrafted human cells never exceeded the initial dose. These data
      suggest that donor cell expansion was inversely regulated by target niche
      parameters and/or transplantation density. Investigation of the response of donor
      cells to the host microenvironment should be a key variable in defining target
      cell dose in pre-clinical models of CNS disease and injury.

PMID- 26298026
TI  - Removal of the anti-cancer drug methotrexate from water by advanced oxidation
      processes: Aerobic biodegradation and toxicity studies after treatment.
AB  - Anti-cancer drugs are discussed as high risk substances in regard to human health
      and considered as problematic for the environment. They are of potential
      environmental relevance due to their poor biodegradability and toxicological
      properties. Methotrexate (MTX) is an antimetabolite that was introduced in the
      pharmaceutical market in the 40's and still today is one of the most consumed
      cytotoxic compounds around the world. In the present study MTX was only partially
      biodegraded in the closed bottle test (CBT). Therefore, it was submitted to three
      different advanced oxidation processes (AOPs): UV/H2O2, UV/Fe(2+)/H2O2 and
      UV/TiO2. The irradiation was carried out with a Hg medium-pressure lamp during
      256min whereas the analytical monitoring was done through LC-UV-MS/MS and DOC
      analysis. MTX was easily removed in all the irradiation experiments, while the
      highest mineralization values and rates were achieved by the UV/Fe(2+)/H2O2
      treatment. The lowest resulted from the UV/H2O2 reactions. The UV/H2O2 treatment
      resulted in little biodegradable transformation products (TPs). However, the same
      treatment resulted in a reduction of the toxicity of MTX by forming less toxic
      TPs. Analysis by LC-UV-MS/MS revealed the existence of nine TPs formed during the
      photo-catalytic treatments. The pH of the solutions decreased from 6.4 (t 0min)
      to 5.15 in the UV/H2O2 and from 6.4 (t 0min) to 5.9 in the UV/TiO2 at the end of
      the experiments. The initial pH of the UV/Fe(2+)/H2O2 experiments was adjusted to
      5 and after the addition of H2O2 the pH decreased to around 3 and remained in
      this range until the end of the treatments. 

PMID- 26298027
TI  - Effective removal of cationic dyes using carboxylate-functionalized cellulose
      nanocrystals.
AB  - A novel carboxylate-functionalized adsorbent (CNM) based on cellulose
      nanocrystals (CNCs) was prepared and adsorptive removal of multiple cationic dyes
      (crystal violet, methylene blue, malachite green and basic fuchsin) were
      investigated. The maximum cationic dyes uptakes ranged from 30.0 to 348.9mgg(-1)
      following the order of: CNM>CNCs>raw cellulose. Furthermore, the removal of
      crystal violet by CNM was investigated representatively where kinetics,
      thermodynamics and isotherm analysis were employed to explain in-depth
      information associated with the adsorption process. The adsorption kinetics
      fitted well to the pseudo-second-order model and thermodynamic analysis revealed
      that the adsorption process was spontaneous and exothermic. Meanwhile, isothermal
      study demonstrated a monolayer adsorption behavior following the Langmuir model
      with a calculated maximum absorption capacity of 243.9mgg(-1), which is higher
      than those of many other reported adsorbents. These findings prefigure the
      promising potentials of CNM as a versatile adsorbent for the efficient removal of
      cationic dyes from wastewater. 

PMID- 26298028
TI  - Thirty-day mortality leads to underestimation of postoperative death after liver
      resection: A novel method to define the acute postoperative period.
AB  - BACKGROUND: Postoperative mortality commonly is defined as death occurring within
      30 days of surgery or during hospitalization. After resection for liver
      malignancies, this definition may result in underreporting, because mortality
      caused by postoperative complications can be delayed as the result of improved
      critical care. The aim of this study was to estimate statistically the acute
      postoperative period (APP) after partial hepatectomy and to compare mortality
      within this phase to standard timestamps. METHODS: From a prospective database,
      784 patients undergoing resection for primary and secondary hepatic malignancies
      between 2003 and 2013 were reviewed. For estimation of APP, a novel statistical
      method applying tests for a constant postoperative hazard was implemented.
      Multivariable mortality analysis was performed. RESULTS: The APP was determined
      to last for 80 postoperative days (95% confidence interval 40-100 days). Within
      this period, 55 patients died (7.0%; 80-day mortality). In comparison, 30-day
      mortality (N = 32, 4.0%) and in-hospital death (N = 39, 5.0%) were relevantly
      less. No patient died between postoperative days 80 and 90. The causes of
      mortality within 30 days and from days 30-80 did not greatly differ, especially
      regarding posthepatectomy liver failure (44% vs 39%, P = .787). Septic
      complications, however, tended to cause late deaths more frequently (43% vs 25%,
      P = .255). Comorbidities (Charlson comorbidity index >= 3; P = .046), increased
      preoperative alanine aminotransferase activity (P = .030), and major liver
      resection (P = .035) were independent risk factors of 80-day mortality.
      CONCLUSION: After liver resection for primary and secondary malignancies, 90-day
      rather than 30-day or in-hospital mortality should be used to avoid
      underreporting of deaths.

PMID- 26298029
TI  - Reliability of hospital cost profiles in inpatient surgery.
AB  - BACKGROUND: With increased policy emphasis on shifting risk from payers to
      providers through mechanisms such as bundled payments and accountable care
      organizations, hospitals are increasingly in need of metrics to understand their
      costs relative to peers. However, it is unclear whether Medicare payments for
      surgery can reliably compare hospital costs. METHODS: We used national Medicare
      data to assess patients undergoing colectomy, pancreatectomy, and open incisional
      hernia repair from 2009 to 2010 (n = 339,882 patients). We first calculated risk
      adjusted hospital total episode payments for each procedure. We then used
      hierarchical modeling techniques to estimate the reliability of total episode
      payments for each procedure and explored the impact of hospital caseload on
      payment reliability. Finally, we quantified the number of hospitals meeting
      published reliability benchmarks. RESULTS: Mean risk-adjusted total episode
      payments ranged from $13,262 (standard deviation [SD] $14,523) for incisional
      hernia repair to $25,055 (SD $22,549) for pancreatectomy. The reliability of
      hospital episode payments varied widely across procedures and depended on sample
      size. For example, mean episode payment reliability for colectomy (mean caseload,
      157) was 0.80 (SD 0.18), whereas for pancreatectomy (mean caseload, 13) the mean
      reliability was 0.45 (SD 0.27). Many hospitals met published reliability
      benchmarks for each procedure. For example, 90% of hospitals met reliability
      benchmarks for colectomy, 40% for pancreatectomy, and 66% for incisional hernia
      repair. CONCLUSION: Episode payments for inpatient surgery are a reliable measure
      of hospital costs for commonly performed procedures, but are less reliable for
      lower volume operations. These findings suggest that hospital cost profiles based
      on Medicare claims data may be used to benchmark efficiency, especially for more
      common procedures.

PMID- 26298030
TI  - The conundrum of the young colon cancer patient.
AB  - BACKGROUND: Colonoscopy has had a major impact on the incidence and survival of
      colon cancer for patients who are screened, usually beginning at the age of 50.
      Meanwhile, the incidence rate of colon cancer is actually increasing in the
      patients younger than 50 while no routine screening is implemented for this age
      group. METHODS: All patients surgically treated for colon cancer (2004-2011)
      without preexisting high-risk characteristics (hereditary nonpolyposis colorectal
      cancer, inflammatory bowel disease) were included (n = 1,015). Age-related
      disparities in baseline disease and outcomes were reviewed. RESULTS: Patients
      younger than 50 years of age (n = 108; 10.6%) had the greatest baseline rates of
      metastatic (20.4% vs 8.0%; P < .001), node-positive disease (54.6% vs 39.4%; P =
      .002), and greater rates of extramural vascular invasion (38.9 vs 29.4%; P =
      .043). Cancer-related mortality also was greatest in this group (28.7 vs 18.4%; P
      = .011). Multivariable Cox regression shows that patients younger than 50 are
      still at significantly greater risk of mortality after adjustment for effects of
      age, baseline AJCC staging, smoking, and comorbidity (hazard ratio: 1.57, 95%
      confidence interval 1.01-2.45; P = .049). DISCUSSION: Patients younger than 50
      present with the most advanced and aggressive disease, giving them the worst
      stage-independent prognosis of all age groups. Potential causes include age
      related differences in tumor biology and underdetection by current screening
      efforts. This raises the question of how to address the conundrum of the young
      colon cancer patient, who often is the proverbial needle in a haystack of young
      patients, with nonspecific gastrointestinal symptoms but who would benefit
      considerably from early detection.

PMID- 26298031
TI  - Entrustment, autonomy, and performance in the operating room.

PMID- 26298032
TI  - Impact of maternal smoking during pregnancy on microvasculature in childhood. The
      Generation R Study.
AB  - BACKGROUND: Fetal exposure to maternal smoking is associated with an adverse
      cardiovascular risk profile in later life. Early microvasculature adaptations
      might be part of the underlying mechanisms for these associations. AIMS: The aim
      of this study was to examine the influence of maternal smoking during pregnancy
      on retinal vessel calibers in children. STUDY DESIGN: We performed a population
      based prospective cohort study among 3564 school-age children. Maternal smoking
      patterns during pregnancy were assessed by questionnaires. OUTCOME MEASURES: At
      the median age of 6.0 years (95% range 5.8, 8.0 years), we measured childhood
      retinal vessel calibers from retinal photographs. RESULTS: No differences were
      observed in childhood retinal arteriolar and venular calibers among offspring
      from mothers who smoked in the first trimester and mothers who continued smoking
      throughout pregnancy, as compared to mothers who did not smoke during pregnancy.
      Also, no dose-dependent associations of the number of cigarettes smoked during
      pregnancy with childhood retinal vessel calibers were present. CONCLUSION:
      Maternal smoking during pregnancy did not influence childhood retinal arteriolar
      and venular calibers. The mechanisms linking fetal smoke exposure with
      cardiovascular risk factors in later life may include other mechanisms than
      structural microvasculature adaptations.

PMID- 26298033
TI  - Morphology, ontogenesis and molecular characterization of Atractos contortus
      Vorosvary, 1950 and Stichotricha aculeata Wrzesniowskiego, 1866 (Ciliophora,
      Stichotrichida) with consideration of their systematic positions.
AB  - Atractos contortus, a rare highly spiralized hypotrich ciliate, has not been
      studied by modern methods. Atractos contortus and Stichotricha aculeata are
      currently assigned to the Spirofildae. A Canadian population of A. contortus and
      an Idaho population of Stichotricha aculeata, were characterized using live
      observation, silver impregnation, scanning electron microscopy, and 18S rDNA
      sequencing. Atractos contortus has two frontal and one buccal cirrus, two
      marginal and two ventral rows arranged in left-handed helices, and four dorsal
      kineties. Left and right marginal rows make two and a half and three turns; left
      and right ventral rows are shortened. Frontoterminal, postoral, transverse and
      caudal cirri are absent. During morphogenesis the parental adoral zone is
      completely retained. Cirral rows replicate by intrakinetal and de novo processes.
      New right marginal and right ventral rows arise from the parental right ventral
      row. The parental right marginal row is morphogenetically inactive. Dorsal
      kineties replicate apokinetally. The parental dorsomarginal kinety and some
      parental marginal cirri persist for some time after cytokinesis.
      Phylogenetically, A. contortus groups with Uroleptus species and not spirofilids.
      The Idaho S. aculeata matches populations from previous reports. Monophyly of the
      Spirofilidae is rejected. Placement of genus Atractos in the family, Atractosidae
      nov. nom. is proposed. 

PMID- 26298034
TI  - Taxonomy and molecular phylogeny of two novel ciliates, with establishment of a
      new genus, Pseudogastrostyla n. g. (Ciliophora, Hypotrichia, Oxytrichidae).
AB  - Two novel hypotrichous ciliates, Pseudogastrostyla flava n. g., n. sp. and
      Urosomoida subtropica n. sp., isolated from Daya Bay Mangrove Park, Huizhou,
      southern China, were observed in vivo and after protargol staining.
      Pseudogastrostyla n. g. is diagnosed by having more than 18 frontal-ventral
      transverse cirri, an indistinct frontoventral row, undulating membranes in
      Oxytricha-pattern and dorsomarginal kinety, but lacking dorsal kinety
      fragmentation during morphogenesis. The monotypic species, P. flava n. sp., is
      characterized by its brownish body colour, brown-yellowish cortical granules
      mostly arranged in groups, frontoventral row terminating near mid-body, and one
      caudal cirrus. Urosomoida subtropica n. sp. can be recognized by having one
      micronucleus located between two macronuclear nodules, four transverse cirri,
      pretransverse ventral cirrus (V/2) anteriorly located, four dorsal kineties and
      three caudal cirri. Phylogenetic analyses based on SSU rRNA gene sequence data
      indicate that Pseudogastrostyla n. g. is nested within the oxytrichids and is
      most closely related to Rubrioxytricha ferruginea, and that Urosomoida subtropica
      n. sp. clusters with Oxytricha elegans rather than the type species, U. agilis.
      Nodal support values are, however, too low to draw any conclusions about the
      molecular systematics of the genus Urosomoida. 

PMID- 26298035
TI  - Quantitative Evaluation of Vascularity Using 2-D Power Doppler Ultrasonography
      May Not Identify Malignancy of the Thyroid.
AB  - The purpose of this study was to evaluate the usefulness of a quantitative
      vascular index in predicting thyroid malignancy. A total of 1309 thyroid nodules
      in 1257 patients (mean age: 50.2 y, range: 18-83 y) were included. The
      vascularity pattern and vascular index (VI) measured by quantification software
      for each nodule were obtained from 2-D power Doppler ultrasonography (US). Gray
      scale US + vascularity pattern was compared with gray-scale US + VI with respect
      to diagnostic performance. Of the 1309 thyroid nodules, 927 (70.8%) were benign
      and 382 (29.2%) were malignant. The area under the receiver operating
      characteristics curve (Az) for gray-scale US (0.82) was significantly higher than
      that for US combined with vascularity pattern (0.77) or VI (0.70, all p < 0.001).
      Quantified VIs were higher in benign nodules, but did not improve the performance
      of 2-D US in diagnosing thyroid malignancy. 

PMID- 26298036
TI  - Additional Targeted Biopsy in Clinically Suspected Prostate Cancer: Prospective
      Randomized Comparison between Contrast-Enhanced Ultrasound and Sonoelastography
      Guidance.
AB  - Our aim was to improve the detection of prostate cancer by evaluating whether
      contrast-enhanced ultrasound (CEUS) or sonoelastography (SE) is more helpful in
      guiding targeted biopsy (TB) performed before systematic biopsy (SB). A total of
      52 patients suspected of having prostate cancer were prospectively included and
      randomly assigned to either the CEUS or SE group. Different, independent
      radiologists performed TB and twelve-core SB. Within each group, cancer detection
      rates based on core number were compared between SB and TB. We evaluated the
      effect of TB on core-based cancer detection rates between the CEUS and SE groups.
      Cancer detection was higher in overall TB cores 16.4% (28/171) than SB cores
      11.4% (71/624) in both groups. In the SE group, TB cores revealed higher cancer
      detection than did SB cores from 4.49% (14/312) to 12.86% (9/70) (p = 0.01).
      Compared with CEUS, SE may improve detection rates when considering additional TB
      guidance methods.

PMID- 26298037
TI  - Evaluation of cytokine and chemokine response elicited by Rv2204c and Rv0753c to
      detect latent tuberculosis infection.
AB  - Latent TB infection (LTBI) is one of the major contributing factors for the high
      incidence of TB in India that in turn significantly contributes to the pool of
      active TB. Hence, identification and treatment of LTBI is of utmost importance.
      Currently, no specific diagnostic test is available for LTBI. Earlier, in our
      immunoproteomic analysis, we identified Rv2204c and Rv0753c protein-containing
      fractions induced significantly higher interferon-gamma (IFN-gamma) response in
      LTBI than in active TB. In this study, we evaluated cytokine and chemokine
      response against M. tuberculosis antigens for improving LTBI identification. Two
      M. tb proteins Rv2204c and Rv0753c were cloned, over expressed in E. coli and
      purified by affinity chromatography. Antigen-specific immune response was
      evaluated in 39 pulmonary TB patients (PTB) and 35 healthy house-hold contacts
      (HHC). After whole blood culture for 6 days, the secretion of cytokines and
      chemokines were quantified in culture supernatants using Enzyme Linked Immune
      Sorbent Assay (ELISA). Antigen specific cytokines such as interferon gamma (IFN
      gamma), interleukin-6 (IL-6), IL-8, IL-12p40 and chemokines like monocyte
      chemotactic proteins MCP-1, MCP-2 were significantly higher in HHC than PTB. In
      contrast to other cytokines, tumor necrosis factor-alpha (TNF)-alpha response was
      significantly increased in PTB compared with HHC. Both Rv2204c and Rv0753c
      antigen specific IFN-gamma response showed 86% positivity in HHC; whereas in PTB,
      these antigens showed 18% and 21% positivity respectively. Rv2204c antigen
      specific IFN-gamma/TNF-alpha response displayed maximum positivity of 91% in HHC
      and minimum positivity of 10% (4/39) in PTB. Rv2204c and Rv0753c specific IFN
      gamma and IFN-gamma/TNF-alpha responses showed the most promising accuracy in
      identifying LTBI.

PMID- 26298038
TI  - Utility of serum ferritin and lactate dehydrogenase as surrogate markers for
      steroid therapy for Mycoplasma pneumoniae pneumonia.
AB  - INTRODUCTION: Patients with severe mycoplasma pneumonia having very high serum
      interleukin-18 levels may require systemic corticosteroid treatment. However, we
      know of no laboratory markers that have been identified to assess the precise
      severity of Mycoplasma pneumoniae pneumonia. Thus, we investigated the usefulness
      of four clinical laboratory tests as severity indicators and surrogate markers
      for initiation of steroid therapy in these patients. PATIENTS AND METHODS: For 22
      Japanese children (including 3 patients who needed systemic corticosteroid
      therapy) diagnosed with Mycoplasma pneumoniae pneumonia, white blood cell counts
      and serum concentrations of interleukin-18, C-reactive protein, lactate
      dehydrogenase, and ferritin were determined in the acute and recovery phases.
      RESULTS: In total, 8 and 14 patients were classified as moderate and mild
      pneumonia, respectively, according to clinical manifestations. The serum
      interleukin-18 level in the acute phase of the pneumonia group was significantly
      higher than that of age-matched controls. Furthermore, serum interleukin-18,
      lactate dehydrogenase and ferritin levels in the acute phase increased in
      parallel with the severity of the pneumonia. The serum ferritin level was also
      higher in the acute phase than in the recovery phase. Positive correlations
      between the levels of serum interleukin-18, lactate dehydrogenase and ferritin
      were observed in the acute phase. CONCLUSIONS: Serum lactate dehydrogenase and
      ferritin levels may be useful as indicators of the severity of pediatric
      Mycoplasma pneumoniae pneumonia for initiation of corticosteroid therapy.

PMID- 26298039
TI  - A pathologically proven case of adult-onset HIV-related lymphocytic interstitial
      pneumonia with acute exacerbation treated with steroid and antiretroviral
      therapy.
AB  - Lymphocytic interstitial pneumonia (LIP) is a rare opportunistic illness in human
      immunodeficiency virus (HIV)-infected adults, although it is relatively common
      among HIV-infected children. Most adult cases have been reported in African and
      Afro-Caribbean patients and few cases have been reported from Asia. Acute
      exacerbation of HIV-related LIP has not been well described. Here we report a
      pathologically proven case of acute exacerbation of adult-onset HIV-related LIP.
      The patient was an African immigrant living in Japan who presented with chronic
      dyspnea and diffuse bilateral pulmonary infiltrates. His clinical, radiological,
      and pathological findings were consistent with those of LIP. After a diagnostic
      surgical lung biopsy, his hypoxemia and pulmonary infiltrates exacerbated rapidly
      over a few days, although his condition had not progressed during the previous
      year. LIP may be an important differential diagnosis among adult patients in
      Asian countries, especially patients of non-Asian ethnicity. 

PMID- 26298040
TI  - Distribution and annual changes in Streptococcus pneumoniae serotypes in adult
      Japanese patients with pneumonia.
AB  - BACKGROUND: Streptococcus pneumoniae is one of the main causative bacteria in
      patients with pneumonia; however, there are no data regarding serotype changes in
      adult patients with pneumonia after the introduction of the pneumococcal vaccine
      (PCV7) for childhood immunization in Japan. We herein evaluated the serotype
      distribution in adult patients with pneumonia. METHODS: This retrospective
      epidemiological study was performed at the University of Occupational and
      Environmental Health, Japan from January 2011 to December 2013. The serotypes of
      pneumococcal isolates obtained from patients with pneumonia were evaluated along
      with the patients' clinical information. RESULTS: A total of 81 patients with
      pneumococcal pneumonia (89 episodes) from whom S. pneumoniae was isolated were
      included. The numbers (percentages) of sample types were as follows: sputum 55
      (61.8%), intratracheal tube suction 15 (16.9%), intrabronchial sampling 5 (5.6%)
      and bronchoalveolar lavage fluid 14 (15.7%). The PCV7 serotypes decreased
      significantly among the patients with pneumococcal pneumonia from 46.4% in 2011
      to 20.0% in 2013 (p < 0.05). Conversely, PCV13 and 23-valent pneumococcal
      polysaccharide vaccination (PPSV23) serotypes other than PCV7 serotypes mildly
      increased during this period. In addition, the frequency of serotypes 19F, 23F
      and 4 (which are covered by PCV7) decreased annually; however, the changes in the
      frequencies of the other serotypes were not significant. DISCUSSION: This study
      demonstrated the yearly decrease of PCV7 serotypes in adult pneumococcal
      pneumonia patients after introducing PCV7 into the childhood immunization
      schedule in Japan. Continued surveillance of pneumococcal serotype changes is
      important for the proper use of different pneumococcal vaccines.

PMID- 26298041
TI  - Increase of 25-hydroxyvitamin D levels after initiation of combination
      antiretroviral therapy.
AB  - Although vitamin D deficiency in HIV patients reported worldwide, the mechanisms
      and the effect of combination antiretroviral therapy (cART) on vitamin D levels
      are unclear. Patients were 50 male Japanese with HIV who visited Teikyo
      University Hospital, Tokyo, Japan. Patients were divided into those receiving
      cART (cART-experienced group, n = 30) and those who had not received cART (cART
      naive group, n = 20). Patients in the cART-experienced group had received
      treatment with cART for more than one year and those in the cART-naive group were
      just about to start cART at study entry. Patients underwent measurement of serum
      25-hydroxyvitamin D (25(OH)D) levels and assessment of clinical factors twice at
      one year intervals. At study entry, 23 (76.7%) in the cART-experienced group and
      19 (95.0%) in the cART-naive group had vitamin D insufficiency or deficiency.
      Mean 25(OH)D values were significantly higher in the cART-experienced group (25.2
      ng/ml vs. 19.3 ng/ml, p = 0.01). However, levels of 25(OH)D at one year increased
      more in the cART-naive group (-1.1 ng/ml vs. 5.0 ng/ml, p = 0.01), with mean
      25(OH)D values in the cART-naive group increasing to match those in the cART
      experienced group. HIV infected patients who initiated cART showed increases in
      vitamin D levels in one year.

PMID- 26298042
TI  - Translation and construct validity of the Trunk Control Measurement Scale in
      children and youths with brain lesions.
AB  - Trunk control is essential for the performance of everyday tasks. Children with
      neurological impairments such as cerebral palsy (CP) or acquired brain injury
      (ABI) commonly show impaired trunk control, which leads to restriction in
      functional activities. The aim of this study was to provide construct validity of
      the German version of the Trunk Control Measurement Scale (TCMS). We investigated
      convergent and discriminant construct validity by comparing the TCMS with the
      Gross Motor Function Classification System (GMFCS) and the modified Timed up and
      Go (mTUG). Several TCMS items were validated with force plate measurements. The
      centre of pressure (COP) parameters included the standard deviation of amplitude,
      the COP displacement and the area. Fifty-two children with CP and ten children
      with ABI (mean age 10.9 years 4.9 months, range 5-18 years, GMFCS levels I-IV)
      participated. Spearman rank correlation coefficients calculated between the TCMS
      and the GMFCS and mTUG amounted to -0.75 and -0.42, respectively. Validating TCMS
      items with COP parameters was difficult. Nevertheless, the results support the
      validity of the TCMS in children with brain lesions. This study provides
      paediatric therapists working in German speaking countries with a valid tool to
      assess impaired trunk control in these children. Although originally designed for
      children with CP, our results show that the TCMS may also be applicable to
      children with ABI, but more research is needed on a larger population. 

PMID- 26298043
TI  - Effects of aging and dual tasking on step adjustments to perturbations in
      visually cued walking.
AB  - Making step adjustments is an essential component of walking. However, the
      ability to make step adjustments may be compromised when the walker's attentional
      capacity is limited. This study compared the effects of aging and dual tasking on
      step adjustments in response to stepping-target perturbations during visually
      cued treadmill walking. Fifteen older adults (69.4 +/- 5.0 years; mean +/- SD)
      and fifteen young adults (25.4 +/- 3.0 years) walked at a speed of 3 km/h on a
      treadmill. Both groups performed visually cued step adjustments in response to
      unpredictable shifts of projected stepping targets in forward (FW), backward (BW)
      or sideward (SW) directions, at different levels of task difficulty [which
      increased as the available response distance (ARD) decreased], and with and
      without dual tasking (auditory Stroop task). In both groups, step adjustments
      were smaller than required. For FW and BW shifts, older adults undershot more
      under dual-task conditions. For these shifts, ARD affected the age groups
      differentially. For SW shifts, larger errors were found for older adults, dual
      tasking and the most difficult ARD. Stroop task performance did not differ
      between groups in all conditions. Older adults have more difficulty than young
      adults to make corrective step adjustments while walking, especially under dual
      tasking conditions. Furthermore, they seemed to prioritize the cognitive task
      over the step adjustment task, a strategy that may pose aging populations at a
      greater fall risk. For comparable task difficulty, the older adults performed
      considerably worse than the young adults, indicating a decreased ability to
      adjust steps under time pressure.

PMID- 26298044
TI  - Processing of visual information compromises the ability of older adults to
      control novel fine motor tasks.
AB  - We performed two experiments to determine whether amplified motor output
      variability and compromised processing of visual information in older adults
      impair short-term adaptations when learning novel fine motor tasks. In Experiment
      1, 12 young and 12 older adults underwent training to learn how to accurately
      trace a sinusoidal position target with abduction-adduction of their index
      finger. They performed 48 trials, which included 8 blocks of 6 trials (the last
      trial of each block was performed without visual feedback). Afterward, subjects
      received an interference task (watched a movie) for 60 min. We tested retention
      by asking subjects to perform the sinusoidal task (5 trials) with and without
      visual feedback. In Experiment 2, 12 young and 10 older adults traced the same
      sinusoidal position target with their index finger and ankle at three distinct
      visual angles (0.25 degrees , 1 degrees  and 5.4 degrees ). In Experiment 1, the
      movement error and variability were greater for older adults during the visual
      feedback trials when compared with young adults. In contrast, during the no
      vision trials, age-associated differences in movement error and variability were
      ameliorated. Short-term adaptations in learning the sinusoidal task were similar
      for young and older adults. In Experiment 2, lower amount of visual feedback
      minimized the age-associated differences in movement variability for both the
      index finger and ankle movements. We demonstrate that although short-term
      adaptations are similar for young and older adults, older adults do not process
      visual information as well as young adults and that compromises their ability to
      control novel fine motor tasks during acquisition, which could influence long
      term retention and transfer.

PMID- 26298045
TI  - Effect of high level of bladder filling on spinal nociception and motoneuronal
      excitability.
AB  - To verify whether high level of bladder distension may counteract the inhibitory
      effect of descending pathways on sacral spinal cord neurons and to investigate
      which spinal circuitries are possibly involved in such a viscero-somatic
      interaction. Nociceptive withdrawal reflex (NWR), cutaneous silent period (CSP),
      and H-reflex were recorded in both lower and upper limbs of twenty-eight healthy
      subjects. Subjects were examined during baseline (empty bladder, no voiding
      desire), high level of bladder filling (urgency desire), and control (empty
      bladder, no voiding desire) sessions. Results showed that the NWR and its related
      pain perception were reduced in the upper limbs, while only a pain perception
      reduction in males was observed in the lower limbs. The H-reflex was inhibited in
      both limbs. No effects were found on the CSP duration. The decrease in both the
      NWR and its related pain perception in the upper limbs confirms the presence of a
      bladder distension-induced descending inhibitory modulation on nociception at
      spinal level. The lack of a similar inhibitory effect in the lower limbs suggests
      that excitatory nociceptive inputs from bladder afferents counterbalance the
      inhibitory effect on sacral spinal cord. The lack of the descending inhibitory
      effect may be a mechanism aimed at forcing the micturition phase to avoid bladder
      damage caused by bladder sovradistension. 

PMID- 26298047
TI  - An acute bleeding metastatic spinal tumor from HCC causes an acute onset of cauda
      equina syndrome.
AB  - Hepatocellular carcinoma (HCC) is an aggressive tumor that frequently occurs in
      the setting of chronic liver disease and cirrhosis. Herein, we describe a case
      where a patient presented with acute onset cauda equina syndrome due to an
      intradural and extramedullary metastatic tumor bleeding from hepatocellular
      carcinoma (HCC). The patient had lower back pain that had radiated to the
      bilateral lower legs for 3 weeks. Then, the patient had experienced an acute
      onset of bilateral lower leg weakness as well as bladder-urinary dysfunction 2
      days before going to the ER. The patient received a laminectomy from the L1 to L4
      vertebra, removing the intradural spinal tumor and hematoma. To the best of our
      knowledge, this is the first reported case of HCC metastasized to the cauda
      equina with tumor bleeding causing cauda equina syndrome. 

PMID- 26298046
TI  - Gaze-grasp coordination in obstacle avoidance: differences between binocular and
      monocular viewing.
AB  - Most adults can skillfully avoid potential obstacles when acting in everyday
      cluttered scenes. We examined how gaze and hand movements are normally
      coordinated for obstacle avoidance and whether these are altered when binocular
      depth information is unavailable. Visual fixations and hand movement kinematics
      were simultaneously recorded, while 13 right-handed subjects reached-to-precision
      grasp a cylindrical household object presented alone or with a potential obstacle
      (wine glass) located to its left (thumb's grasp side), right or just behind it
      (both closer to the finger's grasp side) using binocular or monocular vision.
      Gaze and hand movement strategies differed significantly by view and obstacle
      location. With binocular vision, initial fixations were near the target's centre
      of mass (COM) around the time of hand movement onset, but usually shifted to end
      just above the thumb's grasp site at initial object contact, this mainly being
      made by the thumb, consistent with selecting this digit for guiding the grasp.
      This strategy was associated with faster binocular hand movements and improved
      end-point grip precision across all trials than with monocular viewing, during
      which subjects usually continued to fixate the target closer to its COM despite a
      similar prevalence of thumb-first contacts. While subjects looked directly at the
      obstacle at each location on a minority of trials and their overall fixations on
      the target were somewhat biased towards the grasp side nearest to it, these gaze
      behaviours were particularly marked on monocular vision-obstacle behind trials
      which also commonly ended in finger-first contact. Subjects avoided colliding
      with the wine glass under both views when on the right (finger side) of the
      workspace by producing slower and straighter reaches, with this and the behind
      obstacle location also resulting in 'safer' (i.e. narrower) peak grip apertures
      and longer deceleration times than when the goal object was alone or the obstacle
      was on its thumb side. But monocular reach paths were more variable and
      deceleration times were selectively prolonged on finger-side and behind obstacle
      trials, with this latter condition further resulting in selectively increased
      grip closure times and corrections. Binocular vision thus provided added
      advantages for collision avoidance, known to require intact dorsal cortical
      stream processing mechanisms, particularly when the target of the grasp and
      potential obstacle to it were fairly closely separated in depth. Different
      accounts of the altered monocular gaze behaviour converged on the conclusion that
      additional perceptual and/or attentional resources are likely engaged compared to
      when continuous binocular depth information is available. Implications for people
      lacking binocular stereopsis are briefly considered. 

PMID- 26298048
TI  - Prearrest hypothermia improved defibrillation and cardiac function in a rabbit
      ventricular fibrillation model.
AB  - BACKGROUND: Hypothermia when cardiopulmonary resuscitation begins may help
      achieve defibrillation and return of spontaneous circulation (ROSC), but few data
      are available. OBJECTIVE: The objective of this study was to determine whether
      prearrest hypothermia improved defibrillation and cardiac function in a rabbit
      ventricular fibrillation (VF) model. RESULTS: Thirty-six New Zealand rabbits were
      randomized equally to receive normothermia (Norm) (~39 degrees C), post-ROSC
      hypothermia (~33 degrees C), or prearrest hypothermia (~33 degrees C).
      Ventricular fibrillation was induced by alternating current. After 4 minutes of
      VF, rabbits were defibrillated and given cardiopulmonary resuscitation until ROSC
      or no response (>=30 minutes). Hemodynamics and electrocardiogram were monitored;
      N-terminal pro-brain natriuretic peptideand troponin I were determined by enzyme
      linked immunosorbent assay. Myocardial histology and echocardiographic data were
      evaluated. First-shock achievement of perfusion rhythm was more frequent in
      prearrest than normothermic animals (7/12 vs 1/12; P=.027). After ROSC, dp/dtmax
      was higher in prearrest than normothermic animals (P<.001). Left ventricular end
      systolic pressure was higher in prearrest than normothermic animals (P=.001). At
      240 minutes after ROSC, troponin I and N-terminal pro-brain natriuretic peptide
      were lower in prearrest than normothermic animals (15.74+/-2.26 vs 25.09+/-1.85
      ng/mL and 426+/-23 vs 284+/-45 pg/mL, respectively), the left ventricular
      ejection fraction and cardiac output were lower in the Norm group than other 2
      groups (P<.01). Myocardial histology was more disturbed in normothermic than post
      ROSC and prearrest animals, but was not different in the latter 2 groups.
      CONCLUSIONS: Induction of hypothermia before VF led to improved cardiac function
      in a rabbit VF model through improving achievement of perfusing rhythm by first
      shock defibrillation and facilitating resuscitation.

PMID- 26298049
TI  - Heel compressions quadruple the number of bystanders who can perform chest
      compressions for 10 minutes.
AB  - OBJECTIVE: The objective of the study is to evaluate whether chest compressions
      using the heel provide a more effective method than manual compressions for
      bystanders. METHODS: This is a cross-sectional observational comparison study
      where each subject acted as his or her own control. A 49-person cohort whose age
      distribution approximated that of sudden cardiac arrest victims were asked to
      perform 10 minutes of 5-cm manual compressions on a cardiopulmonary resuscitation
      manikin at 100 compressions per minute. The compression rate and the endurance of
      each subject were recorded. The same subject was then asked to perform 10 minutes
      of heel compressions at the same depth and rate. RESULTS: Sixteen percent of the
      cohort performed compliant manual compressions for 10 minutes vs 65% using heel
      compressions. Twenty-four percent of the subjects were not heavy enough to get
      compliant depth with manual vs 2% with heel compressions, and 6% could not get
      down on the floor to attempt manual compressions. DISCUSSION: Most cardiac
      arrests occur in private residences. If there is a witness, his or her age
      usually approximates that of the victim. Heel compressions are useful in
      situations where a lone rescuer cannot get down on the floor, cannot compress the
      chest to guideline depth because of an infirmity or lack of weight, or becomes
      too tired to continue manual compressions. Heel compressions significantly
      increase the bystander population's ability to provide effective, uninterrupted
      compressions until EMS arrival.

PMID- 26298050
TI  - Unusual cervical spine epidural abscess.
AB  - A 48-year-old man presented to the emergency department with complain of severe
      neck pain and anterior chest pain. Intermittent fever in the recent 2 days was
      also noted. There is a track maker over his left side of neck. The laboratory
      examination showed leukocytosis and high C-reactive protein level. Urine drug
      screen was positive for opiate. Empirical antibiotic administration was given.
      Blood culture grew gram-positive cocci in chain, and there was no vegetation
      found by heart echocardiogram. However, progressive weakness of four limbs was
      noted, and patient even cannot stand up and walk. The patient also complained of
      numbness sensation over bilateral hands and legs, and lower abdomen. Acute urine
      retention occurred. We arranged magnetic resonance imaging survey, which showed
      evidence of inflammatory process involving the retropharyngeal spaces and
      epidural spaces from the skull base to the bony level of T5. Epidural
      inflammatory process resulted in compression of the spinal cord and bilateral
      neural foramen narrowing. Neurosurgeon was consulted. Operation with laminectomy
      and posterior fusion with bone graft and internal fixation was done. Culture of
      epidural abscess and 2 sets of blood culture all yielded methicillin-sensitive
      Staphylococcus aureus. For epidural abscess, the most common involved spine is
      lumbar followed by thoracic and cervical spine. Diagnosis and treatment in the
      drug abusers are still challenging because they lack typical presentation, drug
      compliance, and adequate follow-up and because it is hard to stop drug abuser
      habit. Significant improvement of neurological deficit can be expected in most
      spinal abscess in drug abusers after treatment.

PMID- 26298051
TI  - Subtle anterior subtalar dislocation.
AB  - Subtalar dislocations are uncommon injuries, and anterior subtalar dislocations
      are extremely rare. Only 7 cases have been reported in detail in the literature,
      but all were associated with substantial displacement immediately apparent on
      radiographs. We report a case of a subtle anterior subtalar dislocation that was
      missed on initial plain films but was subsequently treated successfully with
      closed reduction.

PMID- 26298052
TI  - Pediatric acute osteomyelitis in the postvaccine, methicillin-resistant
      Staphylococcus aureus era.
AB  - OBJECTIVE: We sought to describe the causative organisms, bones involved, and
      complications in cases of pediatric osteomyelitis in the postvaccine age and in
      the era of increasing infection with community-associated methicillin-resistant
      Staphylococcus aureus (MRSA). METHODS: We reviewed the medical records of
      children 12 years and younger presenting to our pediatric emergency department
      between January 1, 2003, and December 31, 2012, with the diagnosis of
      osteomyelitis. We reviewed operative cultures, blood cultures, and imaging
      studies. We identified causative organisms, bone(s) involved, time to therapeutic
      antibiotic treatment, and local and hematogenous complications. RESULTS: The most
      common organism identified was methicillin-sensitive S aureus (26/55), followed
      by MRSA (21/55). Seventy-three bone areas were affected in 67 subjects. The most
      common bone area was the femur (24/73). Forty-six subjects had 75 local
      complications. The most common organism in cases with local complications was
      MRSA (49%). Three subjects had hematogenous complications of deep venous
      thrombosis, septic pulmonary embolus, and endophthalmitis. Subjects with
      complications had shorter time to therapeutic antibiotic treatment. When an
      operative culture was done after therapeutic antibiotics were given, an organism
      was identified from the operative culture in 84% of cases. CONCLUSION: Treatment
      of pediatric osteomyelitis should include antibiotic coverage for MRSA. Most
      cases of pediatric osteomyelitis occur in the long bones. Hematogenous
      complications may include deep venous thrombosis and may be related to treatment
      with a central venous catheter. Operative culture yield when antibiotics have
      already been given is high, and antibiotic treatment should not be delayed until
      operative cultures are obtained.

PMID- 26298053
TI  - Proper target depth of an accelerometer-based feedback device during CPR
      performed on a hospital bed: a randomized simulation study.
AB  - PURPOSE: Feedback devices are used to improve chest compression (CC) quality
      related to survival rates in cardiac arrest. However, several studies have shown
      that feedback devices are not sufficiently reliable to ensure adequate CC depth
      on soft surfaces. Here, we determined the proper target depth of feedback (TDF)
      using an accelerometer during cardiopulmonary resuscitation in hospital beds.
      METHODS: In prospective randomized crossover study, 19 emergency physicians
      performed CCs for 2 minutes continuously on a manikin in 2 different beds with 3
      TDFs (5, 6, and 7 cm). We measured CC depth, the proportion of accurate
      compression depths, CC rate, the proportion of incomplete chest decompressions,
      the velocity of CC (CC velocity), the proportion of time spent in CC relative to
      compression plus decompression (duty cycle), and the time spent in CC (CC time).
      RESULTS: Mean (SD) CC depths at TDF 5, 6, and 7 were 45.42 (5.79), 52.68 (4.18),
      and 58.47 (2.48) on one bed and 46.26 (4.49), 53.58 (3.15), and 58.74 (2.10) mm
      on the other bed (all P<.001), respectively. The proportions of accurate
      compression depths and CC velocity at TDF 5, 6, and 7 differed significantly
      according to TDF on both beds (all P<.001).The CC rate, CC time, and proportion
      of incomplete chest decompression did not differ on both beds (all P>.05). The
      duty cycle differed significantly on only B2. CONCLUSIONS: The target depth of
      the real-time feedback device should be at least 6 cm but should not exceed 7 cm
      for optimal CC on patients on hospital beds.

PMID- 26298054
TI  - Delays and errors among pediatric residents during simulated resuscitation
      scenarios using Pediatric Advanced Life Support (PALS) algorithms.

PMID- 26298055
TI  - An unusual infection of cervicofacial area caused by dental pathology: flesh
      eating syndrome.
AB  - Necrotizing fasciitis (NF) of the cervicofacial area is highly rare, but
      physicians should be familiar with the presentation of this situation owing to
      the suddenness of its beginning, the rapidness of its spread, and ending with
      high mortality and morbidity. In this article, 5 patients with NF admitted to
      emergency department with dental pathology history were discussed with a review
      of the literature. The purpose of this case series is to raise awareness about NF
      of the cervicofacial area caused by dental pathologies. Five patients admitted to
      our emergency department between January 2012 and March 2015 and diagnosed as
      having cervicofacial NF were identified. All patients had dental pathologies. The
      parameters of the study were patients' age, sex, complaints, self- and family
      histories, physical examinations' findings, routine laboratory-computed
      tomographic findings, treatment, and complications. Two of the patients were
      older than 70 years. One of the patients was healthy but he lost time because of
      an inappropriate treatment. These 3 patients died. The remaining patients were
      discharged at the end of the prolonged and intensive treatment. Necrotizing
      fasciitis should always be remembered in the diagnosis of the infection of the
      cervicofacial area. Because of difficulty in its diagnosis, a delay in the
      treatment may result in a horrific outcome.

PMID- 26298057
TI  - Intravenous antibiotics for pulmonary exacerbations in people with cystic
      fibrosis.

PMID- 26298056
TI  - Oncolytic viral therapy for neuroblastoma cells with Sindbis virus AR339 strain.
AB  - PURPOSE: With current treatment regimens, high-risk neuroblastoma (NB) remains
      largely incurable. Oncolytic viral therapy uses replication-competent viruses,
      like Sindbis virus (SINV), to kill cancers. The SINV AR339 strain is blood borne
      and relatively non-virulent. We evaluated the feasibility of SINV AR339 for
      treating human NB. METHODS: The cytotoxicity and viral growth of SINV AR339 were
      evaluated for five human NB cell lines, SK-N-SH, IMR-32, LAN-5, GOTO, and RT-BM
      1. SINV-induced apoptosis was confirmed by TUNEL assays and PARP-1 cleavage. In
      vivo effects of SINV on neuroblastoma cell xenografts in nude mice were assessed
      by intratumoral or intravenous SINV inoculation. RESULTS: In five human NB cell
      lines, SINV infections induced remarkable cytotoxicity. The mRNA expressions of
      anti-apoptotic genes, Bcl-2 and Bcl-xL, in LAN-5 and RT-BM-1, which were less
      sensitive to SINV infection, increased in response to SINV infection, while the
      other NB cell lines sensitive to SINV infection failed to respond. In nude mice,
      intratumoral and intravenous SINV inoculations caused significant regression of
      NB xenograft tumors. CONCLUSION: Our results suggested that SINV AR339 was
      significantly oncolytic against human NB. Thus, SINV showed promise as a novel
      therapy for treating NB.

PMID- 26298058
TI  - Assessment of a molecular diagnostic platform for integrated isolation and
      quantification of mRNA in whole blood.
AB  - Implementation of point-of-care tests may facilitate the health management of
      infectious diseases by reducing the timeframe on pathogen identification and host
      response measurements, allowing for immediate diagnosis and guided clinical
      intervention. In this feasibility study, a novel totally integrated and fully
      automated real-time polymerase chain reaction (PCR) platform (IdyllaTM,
      Biocartis) was assessed to determine the mRNA expression levels of multiple genes
      from 1 mL of whole blood. To this purpose, a sample-in result-out assay,
      including mRNA extraction and RT-qPCR-based detection, was ported to the
      platform. The genes used (matrix metallopeptidase 9, olfactomedin 4, NB1
      glycoprotein and lipocalin 2) were previously identified as predictive for
      severity of disease caused by infection with respiratory syncytial virus (RSV).
      The reproducibility and robustness of the prototype assay was determined using
      the blood samples of 21 healthy donors. The data showed that the IdyllaTM
      platform allows for a fast and user-friendly determination of the relative
      expression levels of the four selected mRNA markers. 

PMID- 26298059
TI  - Socioeconomic patterning in the incidence and survival of teenage and young adult
      men aged between 15 and 24 years diagnosed with non-seminoma testicular cancer in
      northern england.
AB  - PURPOSE: Previous research from developed countries has shown a marked increase
      in the incidence of testicular cancer in the past 50 years. This has also been
      demonstrated in northern England, along with improving 5-year survival. The
      present study aims to determine if socioeconomic factors may play a role in both
      etiology and survival from non-seminoma testicular cancer. MATERIALS AND METHODS:
      We extracted all 214 cases of non-seminoma testicular cancer diagnosed in teenage
      and young adult men aged between 15 and 24 years during 1968 to 2006 from the
      Northern Region Young Persons' Malignant Disease Registry, which is a population
      based specialist regional registry. Negative binomial regression was used to
      examine the relationship between incidence and both the Townsend deprivation
      score (and component variables) and small-area population density. Cox regression
      was used to analyze the relationship between survival and both deprivation and
      population density. RESULTS: Decreased incidence was associated with living in
      areas of higher household overcrowding for young adults aged between 20 and 24
      years (relative risk per 1% increase in household overcrowding = 0.79; 95% CI:
      0.66-0.94) but no association was detected for young people aged between 15 and
      19 years. Community-level household unemployment was associated with worse
      survival (hazard ratio per 1% increase in household unemployment = 1.04; 95% CI:
      1.00-1.08). CONCLUSIONS: This study has shown that increased risk of non-seminoma
      testicular cancer in teenage and young adult men may be associated with some
      aspect of more advantaged living. In contrast, greater deprivation is linked with
      worse survival prospects. The study was ecological by design and so these area
      based results may not necessarily apply to individuals.

PMID- 26298060
TI  - A method for moisture measurement in porous media based on epithermal neutron
      scattering.
AB  - A method for moisture measurement in porous media was proposed. A wide beam of
      epithermal neutrons was obtained from a Pu-Be neutron source immersed in a
      cylinder made of paraffin wax. (3)He detectors (four or six) arranged in the
      backward direction of the incident beam were used to record scattered neutrons
      from investigated samples. Experiments of water absorption into clay and silicate
      bricks, and a sand column were investigated by neutron scattering. While the
      samples were absorbing water, scattered neutrons were recorded from fixed
      positions along the water flow direction. It was observed that, at these
      positions scattered neutrons increase as the water uptake increases. Obtained
      results are discussed in terms of the theory of macroscopic flow in porous media.
      It was shown that, the water absorption processes were Fickian and non Fickian in
      the sand column and brick samples, respectively. The advantages of applying the
      proposed method to study fast as well as slow flow processes in porous media are
      discussed. 

PMID- 26298061
TI  - Current status of arsenic exposure and social implication in the Mekong River
      basin of Cambodia.
AB  - To evaluate the current status of arsenic exposure in the Mekong River basin of
      Cambodia, field interview along with urine sample collection was conducted in the
      arsenic-affected area of Kandal Province, Cambodia. Urine samples were analyzed
      for total arsenic concentrations by inductively coupled plasma mass spectrometry.
      As a result, arsenicosis patients (n = 127) had As in urine (UAs) ranging from
      3.76 to 373 ug L(-1) (mean = 78.7 +/- 69.8 ug L(-1); median = 60.2 ug L(-1)).
      Asymptomatic villagers (n = 108) had UAs ranging from 5.93 to 312 ug L(-1) (mean
      = 73.0 +/- 52.2 ug L(-1); median = 60.5 ug L(-1)). About 24.7 % of all
      participants had UAs greater than 100 ug L(-1) which indicated a recent arsenic
      exposure. A survey found that females and adults were more likely to be diagnosed
      with skin sign of arsenicosis than males and children, respectively. Education
      level, age, gender, groundwater drinking period, residence time in the village
      and amount of water drunk per day may influence the incidence of skin signs of
      arsenicosis. This study suggests that residents in Kandal study area are
      currently at risk of arsenic although some mitigation has been implemented. More
      commitment should be made to address this public health concern in rural
      Cambodia. 

PMID- 26298062
TI  - Radiologic assessment of HeartMate II position: Minimal pump migration after long
      term support.
AB  - BACKGROUND: Surgical positioning of the HeartMate II (HMII) left ventricular
      assist device assuring an unobstructed blood flow path is essential for optimal
      device function and hemodynamic support. We report a non-invasive radiologic
      assessment of HMII position after implant and long-term follow-up. METHODS: We
      reviewed 132 consecutive patients (age 64 +/- 14 years; 86% male; 60% destination
      therapy) implanted with an HMII from January 2009 to December 2012 and followed
      for them for up to 4 years. A radiologist measured pump position, pocket depth
      and cannula angles using chest radiography. Changes over time were determined in
      64 of these patients with pairs of radiographs immediately after implant and at
      an average of 2.0 +/- 0.7 years of follow-up. RESULTS: The axis of the pump
      relative to the spine was 92 +/- 10 degrees  at baseline and 94 +/- 9 degrees  at
      2 years (n = 64, p = 0.02), and inflow cannula angles averaged 21 +/- 13 degrees 
      from vertical at baseline and 20 +/- 12 degrees  at 2 years (p = not
      statistically significant). More than 90% of angle measurements showed <15
      degrees  movement over the follow-up duration. There was a small but significant
      superior pump migration from a depth of 12.7 +/- 2.7 cm to 10.4 +/- 2.6 cm (p <
      0.001). There were no cannula obstructions or instances of right ventricular
      assist device use. The 30-day operative mortality was 3.0%. Prolonged inotrope
      dependence occurred in 5.3% (7 of 126) of patients, and low rates of pump
      thrombosis of 0.018 event/patient-year (0 at 3 months) and stroke 0.074
      event/patient-year were noted. CONCLUSION: Non-invasive radiographic measurements
      of surgical pump placement designed to avoid pump and cannula malposition
      demonstrate stable position with minimal pump migration.

PMID- 26298063
TI  - Dramatic Improvement in Juvenile Parkinsonism after Levodopa Treatment in a
      Patient Negative for the PANK2 Mutation.

PMID- 26298064
TI  - Synthesis of well-defined bicapped octahedral iron clusters [((tren) L)2 Fe8
      (PMe2 Ph)2 ](n) (n=0, -1).
AB  - The synthesis of polynuclear clusters with control over size and cluster geometry
      remains an unsolved challenge. Herein, we report the synthesis and
      characterization of open-shell octairon clusters supported by two heptaamine
      ligands [o-H2 NC6 H4 NH(CH2 )2 ]3 N ((tren) LH9 ). The crystal structure of the
      all-ferrous species ([(tren) L)2 Fe8 (PMe2 Ph)2 ] (1) displays a bicapped
      octahedral geometry with Fe?Fe distances ranging from 2.4071(6) to 2.8236(5) A,
      where the ligand amine units are formally in amine, amide, and imide oxidation
      states. Several redox states of the octairon cluster are accessible, as
      ascertained using cyclic voltammetry. The one-electron-reduced clusters [M](+)
      [((tren) L)2 Fe8 (PMe2 Ph)2 ](-) (M=Bu4 N (2 a); (15-crown-5)Na(thf) (2 b)) were
      isolated and characterized. Variable-temperature magnetic susceptibility data
      indicates that the exchange coupling within the [Fe8 ] core is antiferromagnetic
      which is attenuated upon reduction to the mixed valent anion. 

PMID- 26298066
TI  - Multi-residue analysis of veterinary drugs, pesticides and mycotoxins in dairy
      products by liquid chromatography-tandem mass spectrometry using low-temperature
      cleanup and solid phase extraction.
AB  - A multi-class multi-residue analysis method for determination of veterinary
      drugs, pesticides and mycotoxins in dairy products by liquid chromatography
      tandem mass spectrometry (LC-MS/MS) has been established. These 17 classes, a
      total of 40 kinds of target compounds were chosen because their administration to
      food-producing animals is banned or regulated in China and may be potentially
      abused or misused. Samples were extracted with acetonitrile-ethyl acetate-acetic
      acid (49.5+49.5+1, v/v/v). Most of lipids in the extract were removed by low
      temperature cleanup, prior to solid phase extraction on HLB cartridges. The
      quantification and confirmation of the 40 analytes were performed by LC-MS/MS
      with electro-spray ionization (ESI) interface in multiple reaction monitoring
      (MRM) mode. The limits of detection (LODs) and limits of quantification (LOQs)
      were 0.006-0.3MUg/kg and 0.02-1.0MUg/kg, respectively. The spiked recoveries in
      milk, yogurt, milk powder and cheese samples were from 67.3% to 106.9%. The
      repeatability and the within-laboratory reproducibility were less than 12.7% and
      13.9%. Applying this method, our results revealed the presences of
      chloramphenicol, cimeterol, and flunixin at the concentration of 0.027
      0.452MUg/kg in some samples. 

PMID- 26298067
TI  - Differential responses in photosynthesis, growth and biomass yields in two
      mulberry genotypes grown under elevated CO2 atmosphere.
AB  - This study was aimed to examine the responses of two mulberry genotypes (Morus
      alba L.), which include a drought tolerant (DT) Selection-13 (S13) and a drought
      susceptible (DS) Kanva-2 (K2) grown under elevated atmospheric CO2 concentration
      ([CO2]) of 550 MUmol mol(-1). Although both genotypes exhibited positive
      responses to elevated CO2, S13 showed higher light saturated photosynthetic rates
      (A') and apparent quantum efficiency (AQE), suggesting better Rubisco
      carboxylation. Increased water use efficiency (WUEi) in elevated CO2 grown S13
      (ES13) was due to reduced stomatal conductance (gs) and transpiration (E).
      Elevated CO2 significantly increased chlorophyll a fluorescence characteristics
      including maximum quantum yield of primary photochemistry (FV/FM) and performance
      index (PI(ABS)) suggesting an improved photosystem-II efficiency in both
      genotypes compared to their respective controls. Even though ES13 showed superior
      photosynthetic performance, accumulation of soluble and insoluble sugars (starch)
      were significantly low compared to elevated CO2 grown K2 (EK2), demonstrating
      higher sink capacity in ES13, which in turn resulted in better biomass yields. We
      conclude that S13 could be a potential genotype for mulberry-based short rotation
      forestry (SRF) to mitigate increasing atmospheric [CO2] as well as for the
      production of carbon neutral renewable bio-energy.

PMID- 26298065
TI  - Exploiting genomics and natural genetic variation to decode macrophage enhancers.
AB  - The mammalian genome contains on the order of a million enhancer-like regions
      that are required to establish the identities and functions of specific cell
      types. Here, we review recent studies in immune cells that have provided insight
      into the mechanisms that selectively activate certain enhancers in response to
      cell lineage and environmental signals. We describe a working model wherein
      distinct classes of transcription factors define the repertoire of active
      enhancers in macrophages through collaborative and hierarchical interactions, and
      discuss important challenges to this model, specifically providing examples from
      T cells. We conclude by discussing the use of natural genetic variation as a
      powerful approach for decoding transcription factor combinations that play
      dominant roles in establishing the enhancer landscapes, and the potential that
      these insights have for advancing our understanding of the molecular causes of
      human disease. 

PMID- 26298068
TI  - The effects of combined low level laser therapy and mesenchymal stem cells on
      bone regeneration in rabbit calvarial defects.
AB  - OBJECTIVE: This study evaluated the effect of Low Level Laser Therapy (LLLT) and
      Mesenchymal Stem Cells (MSCs) on bone regeneration. BACKGROUND DATA: Although
      several studies evaluated the effects of MSCs and LLLT, there is little
      information available regarding in vivo application of LLLT in conjunction with
      MSCs. METHODS: Forty-eight circular bone defects (6mm in diameter) were prepared
      in the calvaria of 12 New-Zealand white rabbits. The defects of each animal were
      randomly assigned to 4 groups: (C) no treatment; (L) applying LLLT; (SC) filled
      with MSCs; (SCL) application of both MSCs and LLLT. LLL was applied on alternate
      days at wavelength of 810 nm, power density of 0.2 W/cm(2) and a fluency of 4
      J/cm(2) using a Gallium-Aluminum-Arsenide (GaAlAs) diode laser. The animals were
      sacrificed after 3 weeks and then histological samples were evaluated to
      determine the amount of new bone formation and the remaining scaffold and
      inflammation. RESULTS: The histological evaluation showed a statistically
      significant increase in new bone formation of LLLT group relative to the control
      and the other two experimental groups (p<0.05). There was no significant
      difference in bone formation of the control group compared to experimental groups
      filled with MSCs. Laser irradiation had no significant effect on resorption of
      the scaffold material. In addition, inflammation was significantly reduced in
      LLLT group compared to the control defects and the other two experimental groups.
      CONCLUSION: Low level laser therapy could be effective in bone regeneration but
      there is no evidence of a synergistic effect when applied in conjunction with
      MSCs.

PMID- 26298069
TI  - Strut Coverage After Paclitaxel-Eluting Stent Implantation in the Superficial
      Femoral Artery.

PMID- 26298070
TI  - Whole-Body Visualization of Ectopic Bone Formation of Arteries and Skin in
      Pseudoxanthoma Elasticum.

PMID- 26298071
TI  - Native T1 Mapping by 3-T CMR Imaging for Characterization of Chronic Myocardial
      Infarctions.
AB  - OBJECTIVES: The purpose of this study was to investigate whether native T1 maps
      at 3-T can reliably characterize chronic myocardial infarctions (MIs) in patients
      with prior ST-segment elevation myocardial infarction (STEMI) or non-ST-segment
      elevation myocardial infarction (NSTEMI). BACKGROUND: Late gadolinium enhancement
      (LGE) cardiac magnetic resonance is the gold standard for characterizing chronic
      MIs, but it is contraindicated in patients with end-stage chronic kidney disease.
      METHODS: Native T1 and LGE images were acquired at 3-T in patients with prior
      STEMI (n = 13) and NSTEMI (n = 12) at a median of 13.6 years post-MI. Infarct
      location, size, and transmurality were measured using mean +/- 5 SDs thresholding
      criterion from LGE images and T1 maps and compared against one another.
      Independent reviewers assessed visual conspicuity of MIs on LGE images and T1
      maps. RESULTS: Native T1 maps and LGE images were not different for measuring
      infarct size (STEMI: p = 0.46; NSTEMI: p = 0.27) and transmurality (STEMI: p =
      0.13; NSTEMI: p = 0.21) using thresholding criterion. Using thresholding
      criterion, good agreement was observed between LGE images and T1 maps for
      measuring infarct size (STEMI: bias = 0.6 +/- 3.1%; R(2) = 0.93; NSTEMI: bias = 
      0.4 +/- 4.4%; R(2) = 0.85) and transmurality (STEMI: bias = 2.0 +/- 4.2%; R(2) =
      0.89; NSTEMI: bias = -2.7 +/- 7.9%; R(2) = 0.68). Sensitivity and specificity of
      T1 maps for detecting chronic MIs based on thresholding criterion were 89% and
      98%, respectively (STEMI), and 87% and 95%, respectively (NSTEMI). Relative to
      LGE images, the mean visual conspicuity score for detecting chronic MIs was
      significantly lower for T1 maps (p < 0.001 for both cases). Median infarct-to
      remote myocardium contrast-to-noise ratio was 2.5-fold higher for LGE images
      relative to T1 maps (p < 0.001). Sensitivity and specificity of T1 maps for
      visual detection were 60% and 86%, respectively (STEMI), and 64% and 91%
      (NSTEMI), respectively. CONCLUSIONS: Chronic MIs in STEMI and NSTEMI patients can
      be reliably characterized using threshold-based detection on native T1 maps at 3
      T. Visual detection of chronic MIs on native T1 maps in both patient populations
      has high specificity, but modest sensitivity.

PMID- 26298072
TI  - Influence of Coronary Calcification on the Diagnostic Performance of CT
      Angiography Derived FFR in Coronary Artery Disease: A Substudy of the NXT Trial.
AB  - OBJECTIVES: The goal of this study was to examine the diagnostic performance of
      noninvasive fractional flow reserve (FFR) derived from coronary computed
      tomography angiography (CTA) (FFRCT) in relation to coronary calcification
      severity. BACKGROUND: FFRCT has shown promising results in identifying lesion
      specific ischemia. The extent to which the severity of coronary calcification
      affects the diagnostic performance of FFRCT is not known. METHODS: Coronary
      calcification was assessed by using the Agatston score (AS) in 214 patients
      suspected of having coronary artery disease who underwent coronary CTA, FFRCT,
      and FFR (FFR examination was performed in 333 vessels). The diagnostic
      performance of FFRCT (<=0.80) in identifying vessel-specific ischemia (FFR
      <=0.80) was investigated across AS quartiles (Q1 to Q4) and for discrimination of
      ischemia in patients and vessels with a low-mid AS (Q1 to Q3) versus a high AS
      (Q4). Coronary CTA stenosis was defined as lumen reduction >50%. RESULTS: Mean +/
      SD per-patient and per-vessel AS were 302 +/- 468 (range 0 to 3,599) and 95 +/-
      172 (range 0 to 1,703), respectively. There was no statistical difference in
      diagnostic accuracy, sensitivity, or specificity of FFRCT across AS quartiles.
      Discrimination of ischemia by FFRCT was high in patients with a high AS (416 to
      3,599) and a low-mid AS (0 to 415), with no difference in area under the receiver
      operating characteristic curve (AUC) (0.86 [95% confidence interval (CI): 0.76 to
      0.96] vs. 0.92 [95% CI: 0.88 to 0.96]) (p = 0.45). Similarly, discrimination of
      ischemia by FFRCT was high in vessels with a high AS (121 to 1,703) and a low-mid
      AS (0 to 120) (AUC: 0.91 [95% CI: 0.85 to 0.97] vs. 0.95 [95% CI: 0.91 to 0.98];
      p = 0.65). Diagnostic accuracy and specificity of FFRCT were significantly higher
      than for stenosis assessment in each AS quartile at the per-patient (p < 0.001)
      and per-vessel (p < 0.05) level with similar sensitivity. In vessels with a high
      AS, FFRCT exhibited improved discrimination of ischemia compared with coronary
      CTA alone (AUC: 0.91 vs. 0.71; p = 0.004), whereas on a per-patient level, the
      difference did not reach statistical significance (AUC: 0.86 vs. 0.72; p = 0.09).
      CONCLUSIONS: FFRCT provided high and superior diagnostic performance compared
      with coronary CTA interpretation alone in patients and vessels with a high AS.

PMID- 26298073
TI  - OCT-Defined Morphological Characteristics of Coronary Artery Spasm Sites in
      Vasospastic Angina.
AB  - OBJECTIVES: The aim of this study was to define the morphological features of
      coronary artery spasm sites using optical coherence tomography (OCT) in patients
      with vasospastic angina (VSA). BACKGROUND: Plaque characteristics at coronary
      artery spasm sites have not been investigated systematically. METHODS: Sixty-nine
      consecutive patients (80 spasm sites) presenting with VSA who underwent OCT
      imaging were included in this study. Fibrous cap disruption was identified by the
      discontinuation of fibrous cap with or without intraplaque cavity formation. OCT
      defined erosion was established by the presence of thrombus with or without lumen
      irregularity overlying an intact fibrous cap on multiple adjacent OCT frames.
      Other morphological features such as the absence of thrombus with or without
      lumen irregularity and those not in the previously mentioned criteria were also
      documented. RESULTS: Plaque was seen on OCT in 79 of the 80 spasm sites. Fibrous
      cap disruption was detected at 3 sites (4%). OCT-defined erosion was observed at
      21 spasm sites (26%). Thrombus with lumen irregularity was observed in 20 sites,
      whereas 1 site had thrombus without lumen irregularity. Lumen irregularity
      without thrombus was observed at 49 spasm sites (61%). Spontaneous spasm was seen
      more frequently in patients with acute myocardial infarction and out-of-hospital
      cardiac arrest than in patients without these conditions (50.0% vs. 19.3%, p =
      0.025). CONCLUSIONS: Our results show that OCT-defined erosion at spasm sites
      occurred in more than one-fourth of patients in this study. Luminal irregularity
      was observed in nearly two-thirds of the patients without overlying thrombus.
      These findings suggest the potential role of antiplatelet therapy in VSA.

PMID- 26298074
TI  - Association of a 4-Tiered Classification of LV Hypertrophy With Adverse CV
      Outcomes in the General Population.
AB  - OBJECTIVES: This study was performed to determine whether a 4-tiered
      classification of left ventricular hypertrophy (LVH) defines subgroups in the
      general population that are at variable risks of adverse cardiovascular (CV)
      outcomes. BACKGROUND: We recently proposed a 4-tiered classification of LVH where
      eccentric LVH is subdivided into "indeterminate hypertrophy" and "dilated
      hypertrophy" and concentric LVH into "thick hypertrophy" and "both thick and
      dilated hypertrophy," based on the presence of increased left ventricular (LV)
      end-diastolic volume. METHODS: Participants from the Dallas Heart study who
      underwent cardiac magnetic resonance and did not have LV dysfunction or a history
      of heart failure (HF) (n = 2,458) were followed for a median of 9 years for the
      primary outcome of HF or CV death. Multivariable Cox proportional hazards models
      were used to adjust for age, sex, African-American race, hypertension, diabetes,
      and history of CV disease. RESULTS: In the cohort, 70% had no LVH, 404 (16%) had
      indeterminate hypertrophy, 30 (1%) had dilated hypertrophy, 289 (12%) had thick
      hypertrophy, and 7 (0.2%) had both thick and dilated hypertrophy. The cumulative
      incidence of HF or CV death was 2% with no LVH, 1.7% with indeterminate, 16.7%
      with dilated, 11.1% with thick, and 42.9% with both thick and dilated hypertrophy
      (log-rank p < 0.0001). Compared with participants without LVH, those with dilated
      (hazard ratio [HR]: 7.3; 95% confidence interval [CI]: 2.8 to 18.8), thick (HR:
      2.4; 95% CI: 1.4 to 4.0), and both thick and dilated (HR: 5.8; 95% CI: 1.7 to
      19.5) hypertrophy remained at increased risk for HF or CV death after
      multivariable adjustment, whereas the group with indeterminate hypertrophy was
      not (HR: 0.9; 95% CI: 0.4 to 2.2). CONCLUSIONS: In the general population, the 4
      tiered classification system for LVH stratified LVH into subgroups with
      differential risk of adverse CV outcomes.

PMID- 26298075
TI  - Chemical and toxicological characterization of sediments along a Colombian
      shoreline impacted by coal export terminals.
AB  - Extraction, transport and utilization of coal spread out coal dust. Nowadays,
      Colombia is an important producer of this mineral in South America, being the
      Santa Marta area one of the largest coal exporting ports in the country. The aim
      of this work was to assess the pollutants levels and toxicity of shoreline
      sediments from this place. 16 PAHs and 46 elements were measured in nine
      locations during dry and rainy seasons. HepG2 cells were exposed to 1% sediment
      extracts and mRNA expression evaluated for selected genes. PAHs levels were
      greater during the rainy season. The highest ?PAHs (89.9 ng g(-1)) appeared at a
      site located around 300 m far from the coast line at close proximity to the area
      where coal is loaded into cargo vessels for international shipments, being
      naphthalene the most abundant PAH. At Santa Marta Bay port, ?PAHs were 62.8 ng g(
      1) and 72.8 ng g(-1) for dry and rainy seasons, respectively, with greatest
      levels for fluoranthene. Based on sediment standards, most stations have poor
      condition regarding Cr, but moderate contamination on Cu, Pb and Zn. Sediments
      from the port and coal transport sites, the most polluted by PAHs and metals,
      induced CYP1A1 and NQO1 during the dry season. Data showed the sediments from
      this shoreline have bioactive chemicals that determine their toxicological
      profile.

PMID- 26298076
TI  - Rotational output and beam quality evaluations for helical tomotherapy with use
      of a third-party quality assurance tool.
AB  - Our aim was to determine whether a third-party quality assurance (QA) tool was
      suitable for the measurement of rotational output and beam quality in place of on
      board detector signals. A Rotational Therapy Phantom 507 (507 Phantom) was used
      as a QA tool. The rotational output constancy (ROC507) and the beam quality index
      ([Formula: see text]) were evaluated by analysis of signals from an ion chamber
      inserted into the 507 Phantom. On-board detector signals were obtained for
      comparisons with the data from the 507 Phantom. The rotational output
      (ROC(detector)) and beam quality (corrected cone ratio; CCR) were determined by
      analysis of on-board detector signals that were generated by irradiation. The
      tissue phantom ratio at depth 20 and 10 cm (TPR20, 10) was measured with a Farmer
      type ionization chamber inserted in a plastic-slab phantom. For rotational output
      measurement, the correlation coefficient between ROC507 and ROC(detector) values
      was 0.68 (p < 0.001). ROC507 and ROC(detector) values showed a reduced
      coefficient of variation after magnetron replacement, which was done during the
      measurement period. In addition, ROC507 values were reduced significantly along
      with ROC(detector) values after target replacement (p < 0.001). Regarding the
      beam quality index, [Formula: see text] showed a change similar to CCR and an
      increase similar to TPR20, 10 after magnetron/target replacement. This QA tool
      could check for daily rotational output and detect changes in rotational output
      and beam quality caused by magnetron or target failure as well as when on-board
      detector signals were used. Without needing a tomotherapy quality assurance
      license, we could effectively and quantitatively estimate the rotational output
      and beam quality at a low cost.

PMID- 26298077
TI  - Transcriptional and post-transcriptional targeting for enhanced transient gene
      expression in CHO cells.
AB  - OBJECTIVE: To develop a simple approach to increase titers of transient gene
      expression in CHO cells without relying on host cell line engineering as recent
      reports suggest that for PEI-mediated transfections, under optimized conditions,
      DNA delivery into cells and nuclei is not the limiting factor. RESULTS: N, N
      Dimethyl acetamide (DMA) was utilized to enhance transcription. To target post
      transcriptional events, we evaluated the co-expression of various genes involved
      in the unfolded protein response, namely XBP1S, ATF4, CHOP and HSPA5. XBP1S
      overexpression led to a 15-85 % increase in titer for multiple therapeutic
      proteins. Mechanistic studies confirmed that addition of 0.125 % DMA increased
      transgene mRNA levels as expected. However, overexpression of XBP1S had no effect
      on transgene mRNA levels, indicating that it influenced post-transcriptional
      events. Since DMA and XBP1S targeted different pathways, the combination of the
      two approaches led to an additive improvement in protein titer (150-250 % titer
      increase). CONCLUSION: Transcriptional and post-transcriptional pathways of
      transient gene expression can be targeted to increase titers without resorting to
      host cell line engineering in a simple, short, 7 day production process.

PMID- 26298078
TI  - In-lake measures for phosphorus control: The most feasible and cost-effective
      solution for long-term management of water quality in urban lakes.
AB  - Both in-lake and catchment measures designed to reduce phosphorus (P) loading
      were implemented as part of a 12.3 million USD restoration project for the
      Minneapolis Chain of lakes in Minnesota (USA). Treatment wetlands, 'in-pipe'
      measures, and in-lake aluminum sulfate (alum) treatment were applied to restore
      water quality in the four urban lakes. Different alum dosing methods led to
      between 4 and 20+ (modeled) years of water quality improvements in these lakes
      after treatment and only one of the four lakes continues to meet water quality
      goals approximately 25 years after the project started. Due to limited space and
      poor performance, reduction of total external loads was low (1-13%) for three
      lakes. Changes to internal P sediment release rates after application of alum
      correlated well with epilimnetic total P (TP) concentrations in these lakes,
      indicating that improvements in water quality were mainly driven by reduced
      internal loading via in-lake measures. Substantial reductions to external P
      loading were only achieved at Cedar Lake (49%) via conversion of an existing
      natural area to a treatment wetland, but even Cedar Lake is no longer meeting
      management goals. When expressed in terms of dollars spent per unit P removed, in
      lake alum treatment was on average 50 times more effective than in-catchment
      measures. The results of this study indicate that substantial external nutrient
      reductions may not be adequate to sustainably maintain water quality in urban
      lakes and that continued in-lake management of P accumulated in lake sediment
      will not only be necessary, but will also be more cost efficient relative to in
      catchment measures.

PMID- 26298079
TI  - Zeolite-type metal organic frameworks immobilized Eu3+ for cation sensing in
      aqueous environment.
AB  - A novel luminescent lanthanide metal organic framework (Ln-MOF) is synthesized by
      in situ encapsulating Eu(3+) ions to partial replace the transition-metal
      clusters in the channels of CPM-17-Zn nanocrystals. The Eu(3+) functionalized
      zeolite-type MOF hybrid system shows excellent luminescence property and photo
      stability in aqueous environment for the sensitization and protection from the
      host framework. Subsequently, as a highly selective and sensitive sensor, its
      nanocrystals can be used to detect Cd(2+) in aqueous solution. In addition, the
      possible sensing mechanism based on ion exchange is discussed in detail. This
      work is one of the few cases for detecting Cd(2+) in aqueous solution based on a
      zeolite-type MOF. The good fluorescence stability, low detection limit and broad
      linear range in aqueous environment make this probe to be expected to have
      potential application in intracellular sensing and imaging of Cd(2+) potentially.

PMID- 26298080
TI  - Influence of ionic strength and polyelectrolyte concentration on the electrical
      conductivity of suspensions of soft colloidal polysaccharides.
AB  - The electrokinetic properties of carboxymethyldextran, a soft and anionic
      polysaccharide, were analysed in aqueous NaNO3 solutions through measurements of
      the electrical conductivity of the suspensions. The results, which furnish new
      experimental support for the structure of soft polysaccharides in electrolyte
      solution show that the polyion concentration governs the conductance behavior of
      the suspension as the ionic strength decreases. This is particularly evident for
      large polymer concentrations, for which electrical double layer overlap is more
      likely. In contrast, the electrical conductivity of the suspension at high ionic
      strength reduces to the contribution of the ions in solution, as screening of the
      polyion charges is more efficient in such conditions. The applicability of
      Ohshima's general conductivity expression to these electrical conductivity
      measurements was examined, and a major discrepancy against the theory was
      observed. The calculated values of the electrical conductivity deduced on the
      basis of this theory were found to be lower than the experimental ones. Possible
      reasons for this discrepancy are discussed and a numerical model, based on the
      use of a cell approach to account for hydrodynamic and electrical interactions
      between particles, has shown to be a good description of the experimental
      electrokinetic data.

PMID- 26298081
TI  - A different approach to multiplicity-edited heteronuclear single quantum
      correlation spectroscopy.
AB  - A new experiment for recording multiplicity-edited HSQC spectra is presented. In
      standard multiplicity-edited HSQC experiments, the amplitude of CH2 signals is
      negative compared to those of CH and CH3 groups. We propose to reverse the sign
      of (13)C frequencies of CH2 groups in t1 as criteria for editing. Basically, a
      modified [BIRD](r,x) element (Bilinear Rotation Pulses and Delays) is inserted in
      a standard HSQC pulse sequence with States-TPPI frequency detection in t1 for
      this purpose. The modified BIRD element was designed in such a way as to pass or
      stop the evolution of the heteronuclear (1)JHC coupling. This is achieved by
      adding a 180 degrees  proton RF pulse in each of the 1/2J periods. Depending on
      their position the evolution is switched on or off. Usually, the BIRD- element is
      applied on real and imaginary increments of a HSQC experiment to achieve the
      editing between multiplicities. Here, we restrict the application of the modified
      BIRD element to either real or imaginary increments of the HSQC. With this new
      scheme for editing, changing the frequency and/or amplitude of the CH2 signals
      becomes available. Reversing the chemical shift axis for CH2 signals simplifies
      overcrowded frequency regions and thus avoids accidental signal cancellation in
      conventional edited HSQC experiments. The practical implementation is
      demonstrated on the protein Lysozyme. Advantages and limitations of the idea are
      discussed. 

PMID- 26298082
TI  - Spatiotemporal expression of endogenous opioid processing enzymes in mouse uterus
      at peri-implantation.
AB  - Successful implantation requires intimate interactions between a competent
      blastocyst and a receptive uterus. We recently demonstrated that the aberrant
      activation of opioid signaling by exogenous ligands adversely affects
      preimplantation embryonic development and subsequent implantation in mice.
      However, the underlying machinery governing the dynamic homeostasis of the
      endogenous opioid system in the uterus during early pregnancy remains elusive. We
      now show that all three major endogenous opioid precursors are spatiotemporally
      expressed in the uterus during early pregnancy. Moreover, we observe the well
      coordinated expression of the synthetic enzyme prohormone convertases 1/3 (PC1/3)
      at lower levels and of its inhibitor proprotein convertase subtilisin/kexin type
      1 inhibitor (Pcsk1n) and the degrading enzyme membrane metallo-endopeptidase
      (MME) at higher levels in the receptive uterus. Both estrogen and progestin tend
      to reduce the uterine levels of opioid ligand precursors in the ovariectomized
      mouse model. This tight regulation of the endogenous opioid system by PC1/3,
      Pcsk1n and MME has been further confirmed in physiologically related
      pseudopregnancy and delayed implantation mouse models. The coordinated regulation
      of opioid precursor biosynthesis and metabolism helps to create appropriate
      opioid signaling ensuring uterine receptivity for implantation. Thus, endogenous
      uterine opioid levels are primarily determined by the coordinated expressions of
      PC1/3, Pcsk1n and MME under the influence of ovarian progestin and estrogen. Our
      findings raise an additional cautionary note regarding the effects of opioid
      abuse on early pregnancy events. 

PMID- 26298083
TI  - Adaptation and validation of the Spanish version of the graded chronic pain
      scale.
AB  - OBJECTIVE: To adapt the Graded Chronic Pain Scale for use in Primary care
      patients in Spain, and to assess its psychometric properties. METHODS: Clinical
      measures observational study investigating the severity of chronic pain. The
      methodology included a process of translation and back-translation following the
      international guidelines. Study participants were 75 patients who experienced
      lower back pain for more than six months and were sent to Primary Care
      physiotherapy units. Internal consistency, construct validity, test-retest
      reliability, floor and ceiling effects, and answering capacity were analysed.
      RESULTS: The Spanish version of the Graded Chronic Pain Scale had a high internal
      consistency, with a Cronbach's alpha of 0.87 and intraclass correlation
      coefficient of 0.81. Regarding construct validity, it was identified that two
      factors explained 72.37% of the variance. Convergent validity showed a moderate
      positive correlation with the Visual Analogue Scale, the activity avoidance
      subscale of the Tampa Scale of Kinesophobia, the Pain Catastrophizing Scale, the
      Roland-Morris Low Back Pain and Disability Questionnaire, and the FearAvoidance
      Beliefs Questionnaire. A moderate negative correlation was identified with the
      Chronic Pain Self-Efficacy Scale. The mean time of questionnaire administration
      was 2minutes and 28seconds. CONCLUSIONS: The Spanish version of the Graded
      Chronic Pain Scale appears to be a valid, reliable, and useful tool for measuring
      chronic pain at an early stage in Primary Care settings in Spain.

PMID- 26298084
TI  - Pathology and diagnosis of Mycobacterium bovis in naturally infected dromedary
      camels (Camelus dromedarius) in India.
AB  - The present study investigated the pathological features of tuberculosis (TB)
      caused by Mycobacterium bovis and its diagnosis in naturally infected dromedary
      camels from an organized farm in India. During the period of the 5-year study, a
      total of 18 (19.56 %) camels out of 92 examined showed gross lesions compatible
      with TB at post-mortem. The clinical signs and pathological lesions in these
      camels were studied, and the efficacy of different diagnostic tests was also
      assessed. On the basis of occurrence and distribution of gross TB lesions, the
      infected camels revealed two different lesional patterns as pulmonary (n = 15)
      and disseminated (n = 3) form. The histopathology of affected organs revealed
      typical granulomatous lesions wherein the giant cells and acid-fast bacilli were
      occasionally observed in pulmonary form whereas they frequently observed in
      disseminated form. The single intradermal tuberculin test (SIDT) detected TB in
      10 (55.55 %) whereas the Ziehl-Neelsen (ZN) stain and IS6110 PCR from tissue
      lesions detected 13 (72.22 %) and 18 (100 %) of the infected camels,
      respectively. The study suggests that pulmonary form of the TB is more common in
      camels indicating respiratory route as the major source of exposure in camel
      herds. Moreover, very low sensitivity of SIDT was observed which highlights the
      difficulty for confirmation of TB in live camels. 

PMID- 26298085
TI  - Cross-linking oppositely charged oil-in-water emulsions to enhance
      heteroaggregate stability.
AB  - The formation and subsequent enzymatic and chemical cross-linking of
      heteroaggregates from oppositely charged oil-in-water (O/W) emulsions was
      investigated. For this purpose, 10% (w/w) oil-in-water emulsions (d43<1 MUm) were
      prepared at pH 4 using a positively charged emulsifier (Nalpha-lauroyl-L-arginine
      ethyl ester (LAE), cold water fish gelatin, or whey protein isolate) or a
      negatively charged one (sugar beet pectin or Quillaja saponins). The oppositely
      charged emulsions were then combined at a volume ratio of 1:1 and treated with
      laccase or glutaraldehyde in order to further stabilize the electrostatically
      attached aggregates by covalently cross-linking the oppositely charged membranes.
      Emulsions and heteroaggregates were characterized by their rheological
      properties, their surface charge, particle size distribution, and microstructure
      using dynamic and static light scattering as well as confocal laser scanning
      microscopy. Prior to cross-linking, the emulsifiers' stabilization mechanism were
      found to greatly influence the formation of heteroaggregates. Laccase treatment
      (1.34 mU/mL) increased aggregate expansion by ca. 30% for the combined emulsions
      stabilized by Quillaja saponins/whey protein isolate, while combined Quillaja
      saponins/fish gelatin stabilized emulsions remained unaffected. When combined
      emulsions were treated with 50mM glutaraldehyde, aggregate size significantly
      increased 2- and 3-fold, respectively. Thus, our study provides novel insights
      into the enzymatic and chemical cross-linking of heteroaggregates composed of
      oppositely charged O/W emulsions.

PMID- 26298086
TI  - Comparison of different cationized proteins as biomaterials for nanoparticle
      based ocular gene delivery.
AB  - Cationized polymers have been proposed as transfection agents for gene therapy.
      The present work aims to improve the understanding of the potential use of
      different cationized proteins (atelocollagen, albumin and gelatin) as
      nanoparticle components and to investigate the possibility of modulating the
      physicochemical properties of the resulting nanoparticle carriers by selecting
      specific protein characteristics in an attempt to improve current ocular gene
      delivery approaches. The toxicity profiles, as well as internalization and
      transfection efficiency, of the developed nanoparticles can be modulated by
      modifying the molecular weight of the selected protein and the amine used for
      cationization. The most promising systems are nanoparticles based on intermediate
      molecular weight gelatin cationized with the endogenous amine spermine, which
      exhibit an adequate toxicological profile, as well as effective association and
      protection of pDNA or siRNA molecules, thereby resulting in higher transfection
      efficiency and gene silencing than the other studied formulations. 

PMID- 26298087
TI  - The impact of language co-activation on L1 and L2 speech fluency.
AB  - Fluent speech depends on the availability of well-established linguistic
      knowledge and routines for speech planning and articulation. A lack of speech
      fluency in late second-language (L2) learners may point to a deficiency of these
      representations, due to incomplete acquisition. Experiments on bilingual language
      processing have shown, however, that there are strong reasons to believe that
      multilingual speakers experience co-activation of the languages they speak. We
      have studied to what degree language co-activation affects fluency in the speech
      of bilinguals, comparing a monolingual German control group with two bilingual
      groups: 1) first-language (L1) attriters, who have fully acquired German before
      emigrating to an L2 English environment, and 2) immersed L2 learners of German
      (L1: English). We have analysed the temporal fluency and the incidence of
      disfluency markers (pauses, repetitions and self-corrections) in spontaneous film
      retellings. Our findings show that learners to speak more slowly than controls
      and attriters. Also, on each count, the speech of at least one of the bilingual
      groups contains more disfluency markers than the retellings of the control group.
      Generally speaking, both bilingual groups-learners and attriters-are equally
      (dis)fluent and significantly more disfluent than the monolingual speakers. Given
      that the L1 attriters are unaffected by incomplete acquisition, we interpret
      these findings as evidence for language competition during speech production. 

PMID- 26298088
TI  - Commentary on "Transformations in hallucinosis and the receptivity of the
      analyst" by Civitarese.
AB  - After summarizing Civitareses complex and stimulating thoughts, merits of his
      conceptualization are emphazised firstly before coming to drawbacks of it. As a
      supplementary perspective on the conceptualisation (TH) of Civitares the
      commentary is focused on a slightly different approach. Transformation into
      hallucinosis is linked to excessive forms of projective identification., which
      can have massive influence on the analyst, thus pressing him into (behavioral)
      patterns similar to what was phantazised, or hallucinated or deluded by the
      patient about the relationsship. If the analyst is after a shorter or longer
      period able to recognize, how near he is or was to the Patient's deluded or
      hallucinated Constructions of his world, this will give him a further source to
      sense and to examine the patients experience. 

PMID- 26298089
TI  - Personalizing chemotherapy dosing using pharmacological methods.
AB  - PURPOSE: Given the toxic nature and narrow therapeutic index of traditional
      chemotherapeutics, better methods of dose and therapy selection are critical.
      Pharmacological methods, including pharmacogenomics and pharmacokinetics, offer a
      practical method to enrich drug exposure, reduce toxicity, and improve quality of
      life for patients. METHODS: PubMed and key abstracts from the American Society of
      Clinical Oncology (ASCO) and American Association for Cancer Research (AACR) were
      searched until July 2015 for clinical data relating to pharmacogenomic- and/or
      pharmacokinetic-guided dosing of anticancer drugs. RESULTS: Based on the results
      returned from a thorough search of the literature and the plausibility of
      utilizing pharmacogenomic and/or pharmacokinetic methods to personalize
      chemotherapy dosing, we identified several chemotherapeutic agents with the
      potential for therapy individualization. We highlight the available data,
      clinical validity, and utility of using pharmacogenomics to personalize therapy
      for tamoxifen, 5-fluorouracil, mercaptopurine, and irinotecan, in addition to
      using pharmacokinetics to personalize dosing for 5-fluorouracil, busulfan,
      methotrexate, taxanes, and topotecan. CONCLUSION: A concerted effort should be
      made by researchers to further elucidate the role of pharmacological methods in
      personalizing chemotherapy dosing to optimize the risk-benefit profile.
      Clinicians should be aware of the clinical validity, utility, and availability of
      pharmacogenomic- and pharmacokinetic-guided therapies in clinical practice, to
      ultimately allow optimal dosing for each and every cancer patient.

PMID- 26298090
TI  - Expression of NGF, BDNF and their high-affinity receptors in ovine mammary glands
      during development and lactation.
AB  - The distribution of nerve growth factor (NGF), brain-derived neurotrophic factor
      (BDNF) and their high-affinity tyrosine kinase receptors TrkA and TrkB was
      investigated by immunohistochemical method in the mammary gland of ewes from
      prepubertal stage to involution. NGF and BDNF protein expressions were strong
      during development of glands at prepubertal stage and during pregnancy and
      decreased during lactation and involution. The expressions localized in both
      stromal and parenchymal cells of developing gland were mainly arranged in the
      apical side of secretory cells during lactation. These observations were also
      confirmed at transcriptional level by RT-PCR analyses. The highest expression of
      all genes significantly occurred at prepubertal stage. NGF was then down
      regulated from pregnancy to involution, and no statistical differences were
      observed among these stages. The receptor TrkA was also under-expressed from
      pregnancy to involution, and its expression significantly differed between
      pregnancy and 30 days of lactation and also between 30 and 60 days of lactation.
      BDNF was significantly down-regulated at 60 days of lactation in comparison with
      prepubertal stage and again between pregnancy and 30 days of lactation. The
      relative abundance of its receptor, TrkB, showed also a significant down
      regulation at 60 days of lactation in comparison with pregnancy and involution.
      Among the myriad of other molecular signals involved in the mammary gland cycle,
      the local production of neuropeptides and their receptors could be of interest in
      understanding their potential role in mammary biology.

PMID- 26298092
TI  - The SLC25A1-p53 mutant crosstalk.

PMID- 26298091
TI  - Does "difficult patient" status contribute to de facto demedicalization? The case
      of borderline personality disorder.
AB  - A diagnosis of Borderline Personality Disorder (BPD) often signals the
      quintessential "difficult patient" status to clinicians, with at least one
      scholar arguing the condition itself was created to name and group difficult
      patients. While patients who are deemed difficult are often dispreferred for
      care, does this have an impact on their overall status as medicalized patients
      who have successfully achieved a sick role? This study relies on (n = 22) in
      depth interviews with mental health clinicians in the United States from 2012 to
      evaluate how they describe patients with BPD, how the diagnosis of BPD affects
      the treatment clinicians are willing to provide, and the implications for
      patients. My findings suggest patients with BPD are routinely labeled
      "difficult," and subsequently routed out of care through a variety of direct and
      indirect means. This process creates a functional form of demedicalization where
      the actual diagnosis of BPD remains de jure medicalized, but the de facto or
      treatment component of medicalization is harder to secure for patients. 

PMID- 26298093
TI  - A rare knee extensor mechanism injury: Vastus intermedius tendon rupture.
AB  - INTRODUCTION: Quadriceps tendon injuries are rare. There is a limited number of
      studies in the literature, reporting partial quadriceps tendon ruptures. We did
      not find any study reporting an isolated vastus intermedius tendon injury in the
      literature. PRESENTATION OF CASE: A 22 years old professional rugby player with
      the complaints of pain in the right lower limb, decreased range of motion in
      right knee and a mass in the mid-anterior of the right thigh applied following an
      overloading on his hyperflexed knee during a rugby match. T2 sequence magnetic
      resonance images revealed discontinuity in the vastus intermedius tendon and
      intramuscular hematoma. The patient has been conservatively treated. DISCUSSION:
      Quadriceps tendon ruptures generally occur after the 4th decade in the presence
      of degenerative changes. Our case is a young professional rugby player. Isolated
      vastus intermedius tendon rupture is unusual. Conservative treatment is performed
      as the intermedius tendon is in the deepest layer of the quadriceps muscle.
      CONCLUSION: We report the first case of isolated rupture of the vastus
      intermedius tendon in the literature and we claim that disorder may be
      succesfully treated with conservative treatment and adequate physiotheraphy.

PMID- 26298094
TI  - Approach and management of a giant lipoma in the left lumbar region.
AB  - INTRODUCTION: Lipomas are the most common benign tumors of the adipose tissue and
      can be located in any region of the body. In most cases lipomas are small and
      asymptomatic, but they can at times reach considerable dimensions and, depending
      on their anatomic site, hinder movements, get inflamed, cause lymphedema, pain
      and/or a compression syndrome. PRESENTATION OF CASE: We here report the case of
      an otherwise healthy patient who came to our observation with a giant bulk in the
      left lumbar region which had been showing progressive growth in the previous 5-6
      years. Physical examination, ultrasound and MRI were carried out in order to
      characterize the size, vascularization and limits of the lesion. Due to the pain
      and restriction of movement that this bulky lesion caused, surgical excision of
      the lesion was performed. DISCUSSION: Giant lipomas display an important
      differential diagnosis problem with malignant neoplasms, especially liposarcomas,
      with which they share many features; often the final diagnosis rests on
      histological evaluation. We here discuss the diagnostic problems that arise with
      a giant lipoma and all the possible approaches concerning treatment of such a big
      lesion, explaining the reasons of our approach and management of a common tumor
      in our case presenting unusual dimensions and location. CONCLUSION: Our approach
      revealed to be successful in order to nurse our patient's pain, restore the
      mobility and address the aesthetic issues that this lesion caused. Postoperative
      checkups were carried out for one year and no signs of relapse have been
      reported.

PMID- 26298095
TI  - Epithelioid Haemangioendothelioma of the mandibular gingiva: case report and
      literature review.
AB  - INTRODUCTION: Epithelioid hemangioendothelioma (EHE) is a rare vascular neoplasm
      that exhibits the potential for recurrence and metastasis but rarely involves the
      oral cavity. PRESENTATION OF CASE: We report the management and long term follow
      up of recurrent EHE in a 23- year-old woman. The lesion initially presented as a
      small area of erythematous gingival swelling with localised bone loss around the
      lower anterior teeth. It was treated by buccal and lingual stripping of the
      gingival tissues. The patient suffered local recurrence after 7 years and was
      treated with a wider surgical excision of the buccal and lingual gingivae,
      conserving the adjacent teeth and bone with an excellent cosmetic outcome. Over
      21 years later, there have been no further recurrences. DISCUSSION: This case
      highlights the management challenges of EHE and is the only case in the
      literature to have reported a case of mandibular gingivae with a long review
      period of 21 years. CONCLUSION: Oral EHE is an unpredictable lesion with a
      relatively benign course, unlike non-oral EHE where up to one third of cases may
      metastasise. Because of the propensity to recur locally after excision and
      curettage, a wide local excision with close clinical follow has been suggested in
      the literature as the treatment of choice for oral lesions. However, the lack of
      metastases from oral lesions, the small size, mandibular site and bland histology
      in this case suggests that a limited soft tissue excision and bone curettage,
      with long term follow-up would be appropriate for similar gingival lesions in
      future.

PMID- 26298096
TI  - [Prothionamide and PAS doses. Correction to "Consensus document on the diagnosis,
      treatment and prevention of tuberculosis"].

PMID- 26298097
TI  - Prediction of higher cost of antiretroviral therapy (ART) according to clinical
      complexity. A validated clinical index.
AB  - BACKGROUND: The financing of antiretroviral therapy (ART) is generally determined
      by the cost incurred in the previous year, the number of patients on treatment,
      and the evidence-based recommendations, but not the clinical characteristics of
      the population. OBJECTIVE: To establish a score relating the cost of ART and
      patient clinical complexity in order to understand the costing differences
      between hospitals in the region that could be explained by the clinical
      complexity of their population. METHODS: Retrospective analysis of patients
      receiving ART in a tertiary hospital between 2009 and 2011. Factors potentially
      associated with a higher cost of ART were assessed by bivariate and multivariate
      analysis. Two predictive models of "high-cost" were developed. The normalized
      estimated (adjusted for the complexity scores) costs were calculated and compared
      with the normalized real costs. RESULTS: In the Hospital Index, 631 (16.8%) of
      the 3758 patients receiving ART were responsible for a "high-cost" subgroup,
      defined as the highest 25% of spending on ART. Baseline variables that were
      significant predictors of high cost in the Clinic-B model in the multivariate
      analysis were: route of transmission of HIV, AIDS criteria, Spanish nationality,
      year of initiation of ART, CD4+ lymphocyte count nadir, and number of hospital
      admissions. The Clinic-B score ranged from 0 to 13, and the mean value (5.97) was
      lower than the overall mean value of the four hospitals (6.16). CONCLUSIONS: The
      clinical complexity of the HIV patient influences the cost of ART. The Clinic-B
      and Clinic-BF scores predicted patients with high cost of ART and could be used
      to compare and allocate costs corrected for the patient clinical complexity.

PMID- 26298098
TI  - Three-Dimensional Echocardiography: A Powerful New Tool in the Evaluation of
      Mitral Annular Structure and Dynamics.

PMID- 26298099
TI  - Risk-stratified postnatal care of newborns with congenital heart disease
      determined by fetal echocardiography.
AB  - BACKGROUND: Advances in fetal echocardiography have improved recognition of
      congenital heart disease (CHD). Imaging protocols have been developed that
      predict delivery room (DR) risk and anticipated postnatal level of care (LOC).
      The aim of this study was to determine the utility of fetal echocardiography in
      the perinatal management of CHD. METHODS: A retrospective analysis of fetal and
      postnatal records was conducted. The anticipated LOC was assigned by fetal
      echocardiography (LOC 1, nursery consult/outpatient follow-up; LOC 2, stable in
      DR with transfer to cardiac hospital; LOC 3 or 4, DR instability/urgent
      intervention needed). Prenatal diagnoses and LOC assignment were compared with
      postnatal diagnoses, treatment, and short-term outcomes. RESULTS: From 2004 to
      2012, 8,101 fetuses were evaluated; 7,405 were normal. Of 696 with CHD, 101
      terminated, 40 died in utero, and 37 received palliative care. LOC was assigned
      in the remaining 518. Of 219 LOC 1, 195 (89%) had postnatal follow-up. Only two
      required transfer for intervention (LOC 1 sensitivity, 0.9; LOC 1 positive
      predictive value, 0.99). Of 260 assigned LOC 2, 229 (88%) had follow-up. Of
      these, 200 (87%) were transferred for surgery or intervention. The median time to
      admission was 195 min. Twenty-two patients (10%) assigned LOC 2 did not require
      intervention; however, seven (all with D-transposition of the great arteries)
      required catheter intervention before surgery. Hospital survival was 86% (LOC 2
      sensitivity, 0.97; LOC 2 positive predictive value, 0.87). All LOC 3 and 4
      patients had follow-up. Thirty-four (87%) needed urgent intervention, with 100%
      DR and 87% hospital survival (LOC 3 and 4 sensitivity, 0.83; LOC 3 and 4 positive
      predictive value, 0.87). CONCLUSIONS: Fetal echocardiography enables accurate
      postnatal risk stratification in CHD, with the exception of D-transposition of
      the great arteries. LOC 1 assignment facilitated outpatient follow-up; LOC 2
      assignment facilitated transfer for intervention. LOC 3 and 4 patients underwent
      stabilizing intervention or surgery with good short-term outcomes. Given the
      inability to predict need for intervention in D-transposition of the great
      arteries, all such patients should be assigned as LOC 3 or 4. Fetal
      echocardiography with LOC assignment should be used in the planning of postnatal
      care in CHD.

PMID- 26298100
TI  - Reduced gene expression levels after chronic exposure to high concentrations of
      air pollutants.
AB  - We analyzed the ability of particulate matter (PM) and chemicals adsorbed onto it
      to induce diverse gene expression profiles in subjects living in two regions of
      the Czech Republic differing in levels and sources of the air pollution. A total
      of 312 samples from polluted Ostrava region and 154 control samples from Prague
      were collected in winter 2009, summer 2009 and winter 2010. The highest
      concentrations of air pollutants were detected in winter 2010 when the subjects
      were exposed to: PM of aerodynamic diameter <2.5MUm (PM2.5) (70 vs.
      44.9MUg/m(3)); benzo[a]pyrene (9.02 vs. 2.56ng/m(3)) and benzene (10.2 vs.
      5.5MUg/m(3)) in Ostrava and Prague, respectively. Global gene expression analysis
      of total RNA extracted from leukocytes was performed using Illumina Expression
      BeadChips microarrays. The expression of selected genes was verified by
      quantitative real-time PCR (qRT-PCR). Gene expression profiles differed by
      locations and seasons. Despite lower concentrations of air pollutants a higher
      number of differentially expressed genes and affected KEGG (Kyoto Encyclopedia of
      Genes and Genomes) pathways was found in subjects from Prague. In both locations
      immune response pathways were affected, in Prague also neurodegenerative diseases
      related pathways. Over-representation of the latter pathways was associated with
      the exposure to PM2.5. The qRT-PCR analysis showed a significant decrease in
      expression of APEX, ATM, FAS, GSTM1, IL1B and RAD21 in subjects from Ostrava, in
      a comparison of winter 2010 and summer 2009. In Prague, an increase in gene
      expression was observed for GADD45A and PTGS2. In conclusion, high concentrations
      of pollutants in Ostrava were not associated with higher number of differentially
      expressed genes, affected KEGG pathways and expression levels of selected genes.
      This observation suggests that chronic exposure to air pollution may result in
      reduced gene expression response with possible negative health consequences. 

PMID- 26298101
TI  - Influence of heat shock and osmotic stresses on the growth and viability of
      Saccharomyces cerevisiae SUBSC01.
AB  - BACKGROUND: With a preceding scrutiny of bacterial cellular responses against
      heat shock and oxidative stresses, current research further investigated such
      impact on yeast cell. Present study attempted to observe the influence of high
      temperature (44-46  degrees C) on the growth and budding pattern of Saccharomyces
      cerevisiae SUBSC01. Effect of elevated sugar concentrations as another stress
      stimulant was also observed. Cell growth was measured through the estimation of
      the optical density at 600 nm (OD600) and by the enumeration of colony forming
      units on the agar plates up to 450 min. RESULTS: Subsequent transformation in the
      yeast morphology and the cellular arrangement were noticed. A delayed and lengthy
      lag phase was observed when yeast strain was grown at 30, 37, and 40  degrees C,
      while at 32.5  degrees C, optimal growth pattern was noticed. Cells were found to
      lose culturability completely at 46  degrees C whereby cells without the
      cytoplasmic contents were also observed under the light microscope. Thus the
      critical growth temperature was recorded as 45  degrees C which was the highest
      temperature at which S. cerevisiae SUBSC01 could grow. However, a complete growth
      retardation was observed at 45  degrees C with the high concentrations of
      dextrose (0.36 g/l) and sucrose (0.18 g/l). Notably, yeast budding was found at
      44 and 45  degrees C up to 270 min of incubation, which was further noticed to be
      suppressed at 46  degrees C. CONCLUSIONS: Present study revealed that the optimal
      and the critical growth temperatures of S. cerevisiae SUBSC01 were 32.5 and 45 
      degrees C, respectively; and also projected on the inhibitory concentrations of
      sugars on yeast growth at that temperature.

PMID- 26298102
TI  - Overexpression of a Brassica campestris HSP70 in tobacco confers enhanced
      tolerance to heat stress.
AB  - Heat shock proteins (HSPs) exist extensively in eukaryotes and are conserved
      molecular chaperones with important contribution to plant's survival under
      environmental stresses. Here, the cloning and characterization of one
      complementary DNA (cDNA) designated as BcHSP70 from young seedlings of Brassica
      campestris were reported in the present work. Bioinformatic analysis revealed
      that BcHSP70 belongs to the plant HSP gene family and had the closest
      relationship with HSP70-4 from Arabidopsis thaliana. Constitutive overexpression
      of BcHSP70 in tobacco obviously conferred tolerance to heat stress by affecting
      different plant physiological parameters. In our study, transgenic tobaccos
      exhibited higher chlorophyll content than wild-type control when exposed to heat
      stress. Superoxide dismutase (SOD) and peroxidase (POD) activities, which were
      helpful to decrease the damage to the membrane system, were significantly higher
      in transformants compared to wild-type lines. Meanwhile, lower comparative
      electrical conductivity and malondialdehyde (MDA) content and higher proline and
      soluble sugar accumulation were found in transgenic tobaccos than in wild-type
      lines. All these above results indicated that this isolated BcHSP70 cDNA owned
      the ability to improve the tolerance to heat stress in transgenic tobacco, which
      provides helpful information and good basement to culture new robust B.
      campestris variety resistant to high-temperature stress by molecular breeding in
      the future. 

PMID- 26298104
TI  - Erratum to: Metal artifact suppression at the hip: diagnostic performance at 3.0
      T versus 1.5 Tesla.

PMID- 26298103
TI  - Sonography of chondral print on humeral head.
AB  - OBJECTIVE: The aim of this study is to determine the diagnostic accuracy of
      sonography in order to identify the chondral print on the humeral head. MATERIALS
      AND METHODS: In total, 44 patients who had already been candidates for
      arthroscopic surgery were prospectively studied with ultrasound to assess the
      presence of humeral subchondral erosion at the level of the biceps pulley; no
      patient had undergone previous surgery or radiographic calcification of rotator
      cuff tendons. Using arthroscopy as the reference standard the sensitivity,
      specificity, positive predictive, negative predictive and diagnostic accuracy
      values were calculated. RESULTS: Of the 44 patients, arthroscopy showed the
      humeral chondral print in 30 patients. Of the 30 arthroscopy proven humeral
      chondral prints, ultrasound identified 28 subchondral erosions at the same level,
      with two false negatives. One of the 14 patients without arthroscopic humeral
      chondral print was positive for subchondral erosion at ultrasound. The
      sensitivity, specificity, positive predictive, negative predictive, and
      diagnostic accuracy values of ultrasound were respectively of 93, 93, 96, 87 and
      93%. CONCLUSION: Ultrasound has a good diagnostic accuracy in identifying the
      chondral print sign.

PMID- 26298105
TI  - Endovascular management of IVC syndrome after IVC filter placement.
AB  - Approximately 60,000-100,000 Americans die from deep venous thrombosis or
      pulmonary embolism annually, while the overall estimate of individuals affected
      is 30,000-600,000. Inferior vena cava (IVC) filter placement has emerged as a
      break-through endovascular technique which has gained increasing acceptance and
      has probably saved thousands of lives by preventing fatal thromboembolic events.
      However, in the absence of a national IVC filter registry an accurate estimate of
      device complications is currently unavailable. We present a case of symptomatic
      IVC syndrome due to IVC interruption in a patient with a non-retrievable IVC
      filter. This patient was initially managed with balloon angioplasty and
      mechanical thrombectomy with suboptimal results and subsequently with stent
      placement through the IVC filter.

PMID- 26298106
TI  - Communication: Observation of local-bender eigenstates in acetylene.
AB  - We report the observation of eigenstates that embody large-amplitude, local
      bending vibrational motion in acetylene by stimulated emission pumping
      spectroscopy via vibrational levels of the S1 state involving excitation in the
      non-totally symmetric bending modes. The N(b) = 14 level, lying at 8971.69 cm(-1)
      (J = 0), is assigned on the basis of degeneracy due to dynamical symmetry
      breaking in the local-mode limit. The level pattern for the N(b) = 16 level,
      lying at 10 218.9 cm(-1), is consistent with expectations for increased
      separation of l = 0 and 2 vibrational angular momentum components. Increasingly
      poor agreement between our observations and the predicted positions of these
      levels highlights the failure of currently available normal mode effective
      Hamiltonian models to extrapolate to regions of the potential energy surface
      involving large-amplitude displacement along the acetylene ? vinylidene
      isomerization coordinate.

PMID- 26298107
TI  - Communication: Spectroscopic consequences of proton delocalization in OCHCO+.
AB  - Even though quartic force fields (QFFs) and highly accurate coupled cluster
      computations describe the OCHCO(+) cation at equilibrium as a complex between
      carbon monoxide and the formyl cation, two notable and typical interstellar and
      atmospheric molecules, the prediction from the present study is that the
      equilibrium C(infinityv) structure is less relevant to observables than the
      saddle-point D(infinityh) structure. This is the conclusion from diffusion Monte
      Carlo and vibrational self-consistent field/virtual state configuration
      interaction calculations utilizing a semi-global potential energy surface. These
      calculations demonstrate that the proton "rattle" motion (nu6) has
      centrosymmetric delocalization of the proton over the D(infinityh) barrier lying
      only 393.6 cm(-1) above the double-well OCHCO(+) C(infinityv) minima. As a
      result, this molecule will likely appear Dinfinityh, and the rotational spectrum
      will be significantly dimmer than the computed equilibrium 2.975 D center-of-mass
      dipole moment indicates. However, the proton transfer fundamental, determined to
      be at roughly 300 cm(-1), has a very strong intensity. This prediction as well as
      those of other fundamentals should provide useful guides for laboratory detection
      of this cation. Finally, it is shown that the two highest energy QFF-determined
      modes are actually in good agreement with their vibrational configuration
      interaction counterparts. These high-level quantum chemical methods provide novel
      insights into this fascinating and potentially common interstellar molecule.

PMID- 26298108
TI  - Communication: Analytic continuation of the virial series through the critical
      point using parametric approximants.
AB  - The mathematical structure imposed by the thermodynamic critical point motivates
      an approximant that synthesizes two theoretically sound equations of state: the
      parametric and the virial. The former is constructed to describe the critical
      region, incorporating all scaling laws; the latter is an expansion about zero
      density, developed from molecular considerations. The approximant is shown to
      yield an equation of state capable of accurately describing properties over a
      large portion of the thermodynamic parameter space, far greater than that covered
      by each treatment alone. 

PMID- 26298109
TI  - Modeling of ultrafast time-resolved fluorescence applied to a weakly coupled
      chromophore pair.
AB  - We present theory for calculating the third-order non-linear response function of
      a molecular aggregate in the weak inter-chromophore coupling regime. This
      approach is based on the perturbative expansion of the system evolution with
      respect to the resonance coupling, while the system-bath interaction is treated
      non-perturbatively by means of cumulant expansion. An explicit expression for the
      time-resolved fluorescence signal is then obtained. This allows us to investigate
      the ultrafast time-dependent Stokes shift, signatures of coherent dynamics, and
      the excitonic polaron formation in the excited state of the aggregate. Numerical
      simulations of the time-resolved fluorescence spectra of a pair of coupled
      molecules demonstrate these effects. 

PMID- 26298110
TI  - Generalized quantum kinetic expansion: Higher-order corrections to
      multichromophoric Forster theory.
AB  - For a general two-cluster energy transfer network, a new methodology of the
      generalized quantum kinetic expansion (GQKE) method is developed, which predicts
      an exact time-convolution equation for the cluster population evolution under the
      initial condition of the local cluster equilibrium state. The cluster-to-cluster
      rate kernel is expanded over the inter-cluster couplings. The lowest second-order
      GQKE rate recovers the multichromophoric Forster theory (MCFT) rate. The higher
      order corrections to the MCFT rate are systematically included using the
      continued fraction resummation form, resulting in the resummed GQKE method. The
      reliability of the GQKE methodology is verified in two model systems, revealing
      the relevance of higher-order corrections. 

PMID- 26298111
TI  - Restricted and unrestricted non-Hermitian Hartree-Fock: Theory, practical
      considerations, and applications to metastable molecular anions.
AB  - This work describes the implementation and applications of non-Hermitian self
      consistent field (NH-SCF) theory with complex basis functions for the ab initio
      computation of positions and widths of shape resonances in molecules. We utilize
      both the restricted open-shell and the previously unexplored spin-unrestricted
      variants to compute Siegert energies of several anionic shape resonances in small
      diatomic and polyatomic molecules including carbon tetrafluoride which has been
      the subject of several recent experimental studies. The computation of general
      molecular properties from a non-Hermitian wavefunction is discussed, and a
      density-based analysis is applied to the (2)B1 shape resonance in formaldehyde.
      Spin-unrestricted NH-SCF is used to compute a complex potential energy surface
      for the carbon monoxide anion which correctly describes dissociation. 

PMID- 26298112
TI  - Multi-reference approach to the calculation of photoelectron spectra including
      spin-orbit coupling.
AB  - X-ray photoelectron spectra provide a wealth of information on the electronic
      structure. The extraction of molecular details requires adequate theoretical
      methods, which in case of transition metal complexes has to account for effects
      due to the multi-configurational and spin-mixed nature of the many-electron wave
      function. Here, the restricted active space self-consistent field method
      including spin-orbit coupling is used to cope with this challenge and to
      calculate valence- and core-level photoelectron spectra. The intensities are
      estimated within the frameworks of the Dyson orbital formalism and the sudden
      approximation. Thereby, we utilize an efficient computational algorithm that is
      based on a biorthonormal basis transformation. The approach is applied to the
      valence photoionization of the gas phase water molecule and to the core
      ionization spectrum of the [Fe(H2O)6](2+) complex. The results show good
      agreement with the experimental data obtained in this work, whereas the sudden
      approximation demonstrates distinct deviations from experiments. 

PMID- 26298113
TI  - The effects of intrinsic noise on the behaviour of bistable cell regulatory
      systems under quasi-steady state conditions.
AB  - We analyse the effect of intrinsic fluctuations on the properties of bistable
      stochastic systems with time scale separation operating under quasi-steady state
      conditions. We first formulate a stochastic generalisation of the quasi-steady
      state approximation based on the semi-classical approximation of the partial
      differential equation for the generating function associated with the chemical
      master equation. Such approximation proceeds by optimising an action functional
      whose associated set of Euler-Lagrange (Hamilton) equations provides the most
      likely fluctuation path. We show that, under appropriate conditions granting time
      scale separation, the Hamiltonian can be re-scaled so that the set of Hamilton
      equations splits up into slow and fast variables, whereby the quasi-steady state
      approximation can be applied. We analyse two particular examples of systems whose
      mean-field limit has been shown to exhibit bi-stability: an enzyme-catalysed
      system of two mutually inhibitory proteins and a gene regulatory circuit with
      self-activation. Our theory establishes that the number of molecules of the
      conserved species is order parameters whose variation regulates bistable
      behaviour in the associated systems beyond the predictions of the mean-field
      theory. This prediction is fully confirmed by direct numerical simulations using
      the stochastic simulation algorithm. This result allows us to propose strategies
      whereby, by varying the number of molecules of the three conserved chemical
      species, cell properties associated to bistable behaviour (phenotype, cell-cycle
      status, etc.) can be controlled. 

PMID- 26298114
TI  - Nuclear velocity perturbation theory for vibrational circular dichroism: An
      approach based on the exact factorization of the electron-nuclear wave function.
AB  - The nuclear velocity perturbation theory (NVPT) for vibrational circular
      dichroism (VCD) is derived from the exact factorization of the electron-nuclear
      wave function. This new formalism offers an exact starting point to include
      correction terms to the Born-Oppenheimer (BO) form of the molecular wave
      function, similar to the complete-adiabatic approximation. The corrections depend
      on a small parameter that, in a classical treatment of the nuclei, is identified
      as the nuclear velocity. Apart from proposing a rigorous basis for the NVPT, we
      show that the rotational strengths, related to the intensity of the VCD signal,
      contain a new contribution beyond-BO that can be evaluated with the NVPT and that
      only arises when the exact factorization approach is employed. Numerical results
      are presented for chiral and non-chiral systems to test the validity of the
      approach. 

PMID- 26298115
TI  - Should thermostatted ring polymer molecular dynamics be used to calculate thermal
      reaction rates?
AB  - We apply Thermostatted Ring Polymer Molecular Dynamics (TRPMD), a recently
      proposed approximate quantum dynamics method, to the computation of thermal
      reaction rates. Its short-time transition-state theory limit is identical to
      rigorous quantum transition-state theory, and we find that its long-time limit is
      independent of the location of the dividing surface. TRPMD rate theory is then
      applied to one-dimensional model systems, the atom-diatom bimolecular reactions H
      + H2, D + MuH, and F + H2, and the prototypical polyatomic reaction H + CH4.
      Above the crossover temperature, the TRPMD rate is virtually invariant to the
      strength of the friction applied to the internal ring-polymer normal modes, and
      beneath the crossover temperature the TRPMD rate generally decreases with
      increasing friction, in agreement with the predictions of Kramers theory. We
      therefore find that TRPMD is approximately equal to, or less accurate than, ring
      polymer molecular dynamics for symmetric reactions, and for certain asymmetric
      systems and friction parameters closer to the quantum result, providing a basis
      for further assessment of the accuracy of this method. 

PMID- 26298117
TI  - Development of highly accurate approximate scheme for computing the charge
      transfer integral.
AB  - The charge transfer integral is a key parameter required by various theoretical
      models to describe charge transport properties, e.g., in organic semiconductors.
      The accuracy of this important property depends on several factors, which include
      the level of electronic structure theory and internal simplifications of the
      applied formalism. The goal of this paper is to identify the performance of
      various approximate approaches of the latter category, while using the high level
      equation-of-motion coupled cluster theory for the electronic structure. The
      calculations have been performed on the ethylene dimer as one of the simplest
      model systems. By studying different spatial perturbations, it was shown that
      while both energy split in dimer and fragment charge difference methods are
      equivalent with the exact formulation for symmetrical displacements, they are
      less efficient when describing transfer integral along the asymmetric alteration
      coordinate. Since the "exact" scheme was found computationally expensive, we
      examine the possibility to obtain the asymmetric fluctuation of the transfer
      integral by a Taylor expansion along the coordinate space. By exploring the
      efficiency of this novel approach, we show that the Taylor expansion scheme
      represents an attractive alternative to the "exact" calculations due to a
      substantial reduction of computational costs, when a considerably large region of
      the potential energy surface is of interest. Moreover, we show that the Taylor
      expansion scheme, irrespective of the dimer symmetry, is very accurate for the
      entire range of geometry fluctuations that cover the space the molecule accesses
      at room temperature. 

PMID- 26298116
TI  - Constant-complexity stochastic simulation algorithm with optimal binning.
AB  - At the molecular level, biochemical processes are governed by random interactions
      between reactant molecules, and the dynamics of such systems are inherently
      stochastic. When the copy numbers of reactants are large, a deterministic
      description is adequate, but when they are small, such systems are often modeled
      as continuous-time Markov jump processes that can be described by the chemical
      master equation. Gillespie's Stochastic Simulation Algorithm (SSA) generates
      exact trajectories of these systems, but the amount of computational work
      required for each step of the original SSA is proportional to the number of
      reaction channels, leading to computational complexity that scales linearly with
      the problem size. The original SSA is therefore inefficient for large problems,
      which has prompted the development of several alternative formulations with
      improved scaling properties. We describe an exact SSA that uses a table data
      structure with event time binning to achieve constant computational complexity
      with respect to the number of reaction channels for weakly coupled reaction
      networks. We present a novel adaptive binning strategy and discuss optimal
      algorithm parameters. We compare the computational efficiency of the algorithm to
      existing methods and demonstrate excellent scaling for large problems. This
      method is well suited for generating exact trajectories of large weakly coupled
      models, including those that can be described by the reaction-diffusion master
      equation that arises from spatially discretized reaction-diffusion processes. 

PMID- 26298118
TI  - Coupled-cluster theory for atoms and molecules in strong magnetic fields.
AB  - An implementation of coupled-cluster (CC) theory to treat atoms and molecules in
      finite magnetic fields is presented. The main challenges for the implementation
      stem from the magnetic-field dependence in the Hamiltonian, or, more precisely,
      the appearance of the angular momentum operator, due to which the wave function
      becomes complex and which introduces a gauge-origin dependence. For this reason,
      an implementation of a complex CC code is required together with the use of gauge
      including atomic orbitals to ensure gauge-origin independence. Results of coupled
      cluster singles-doubles-perturbative-triples (CCSD(T)) calculations are presented
      for atoms and molecules with a focus on the dependence of correlation and binding
      energies on the magnetic field. 

PMID- 26298119
TI  - Explicitly correlated similarity transformed equation-of-motion coupled-cluster
      method.
AB  - Similarity transformed equation-of-motion method, based on linearly approximated
      explicitly correlated coupled-cluster singles and doubles [CCSD(F12)] model, has
      been formulated and implemented. An extension of similarity transformation
      operator is introduced in order to treat short-range correlation effects for
      excited states. Additionally, effective reduction of the number of active
      virtuals can be obtained by such modification. Numerical tests for sets of
      valence and Rydberg excited states of several molecules are conducted.
      Statistical measures of errors in excitation energies show that explicitly
      correlated results are accurate up to 0.1 e.V already at a double-zeta level
      compared to those in the complete basis set limit, if the excitation energy is
      not too close to an ionization threshold. An example of long-range charge
      transfer excitation is also considered and highly accurate results are obtained. 

PMID- 26298120
TI  - On iterative path integral calculations for a system interacting with a shifted
      dissipative bath.
AB  - Real-time path integral calculations for the propagation of a system in contact
      with a harmonic dissipative environment often employ the iterative quasi
      adiabatic propagator path integral (i-QuAPI) methodology. We compare two simple
      ways of applying this methodology to a bath initially in equilibrium with the
      localized state of the system (e.g., the donor in the case of charge transfer).
      The first way involves modifying the phase of the system via a time-local phase
      given in terms of integrals of the spectral density or in terms of the
      coefficients entering the QuAPI-discretized influence functional. In the
      iterative decomposition of the path integral, this approach requires consistent
      memory truncation to avoid extremely slow convergence. The second, alternative
      approach involves shifting the coordinate of the system, to bring the donor state
      in equilibrium with the bath, and requires no further modification of the i-QuAPI
      algorithm. 

PMID- 26298121
TI  - Hyperdynamics boost factor achievable with an ideal bias potential.
AB  - Hyperdynamics is a powerful method to significantly extend the time scales
      amenable to molecular dynamics simulation of infrequent events. One outstanding
      challenge, however, is the development of the so-called bias potential required
      by the method. In this work, we design a bias potential using information about
      all minimum energy pathways (MEPs) out of the current state. While this approach
      is not suitable for use in an actual hyperdynamics simulation, because the
      pathways are generally not known in advance, it allows us to show that it is
      possible to come very close to the theoretical boost limit of hyperdynamics while
      maintaining high accuracy. We demonstrate this by applying this MEP-based
      hyperdynamics (MEP-HD) to metallic surface diffusion systems. In most cases, MEP
      HD gives boost factors that are orders of magnitude larger than the best existing
      bias potential, indicating that further development of hyperdynamics bias
      potentials could have a significant payoff. Finally, we discuss potential
      practical uses of MEP-HD, including the possibility of developing MEP-HD into a
      true hyperdynamics. 

PMID- 26298122
TI  - Adiabatic theory for anisotropic cold molecule collisions.
AB  - We developed an adiabatic theory for cold anisotropic collisions between slow
      atoms and cold molecules. It enables us to investigate the importance of the
      couplings between the projection states of the rotational motion of the atom
      about the molecular axis of the diatom. We tested our theory using the recent
      results from the Penning ionization reaction experiment (4)He(1s2s (3)S) +
      HD(1s(2)) -> (4)He(1s(2)) + HD(+)(1s) + e(-) [Lavert-Ofir et al., Nat. Chem. 6,
      332 (2014)] and demonstrated that the couplings have strong effect on positions
      of shape resonances. The theory we derived provides cross sections which are in a
      very good agreement with the experimental findings. 

PMID- 26298123
TI  - Efficient treatment of induced dipoles.
AB  - Most existing treatments of induced dipoles in polarizable molecular mechanics
      force field calculations use either the self-consistent variational method, which
      is solved iteratively, or the "direct" approximation that is non-iterative as a
      result of neglecting coupling between induced dipoles. The variational method is
      usually implemented using assumptions that are only strictly valid under tight
      convergence of the induced dipoles, which can be computationally demanding to
      enforce. In this work, we discuss the nature of the errors that result from
      insufficient convergence and suggest a strategy that avoids such problems. Using
      perturbation theory to reintroduce the mutual coupling into the direct algorithm,
      we present a computationally efficient method that combines the precision of the
      direct approach with the accuracy of the variational approach. By analyzing the
      convergence of this perturbation series, we derive a simple extrapolation formula
      that delivers a very accurate approximation to the infinite order solution at the
      cost of only a few iterations. We refer to the new method as extrapolated
      perturbation theory. Finally, we draw connections to our previously published
      permanent multipole algorithm to develop an efficient implementation of the
      electric field and Thole terms and also derive some necessary, but not
      sufficient, criteria that force field parameters must obey. 

PMID- 26298124
TI  - Dynamics of gradient formation by intracellular shuttling.
AB  - A number of important cellular functions rely on the formation of intracellular
      protein concentration gradients. Experimental studies discovered a number of
      mechanisms for the formation of such gradients. One of the mechanisms relies on
      the intracellular shuttling of a protein that interconverts between the two
      states with different diffusivities, under the action of two enzymes, one of
      which is localized to the plasma membrane, whereas the second is uniformly
      distributed in the cytoplasm. Recent work reported an analytical solution for the
      steady state gradient in this mechanism, obtained in the framework of a one
      dimensional reaction-diffusion model. Here, we study the dynamics in this model
      and derive analytical expressions for the Laplace transforms of the time
      dependent concentration profiles in terms of elementary transcendental functions.
      Inverting these transforms numerically, one can obtain time-dependent
      concentration profiles of the two forms of the protein. 

PMID- 26298125
TI  - The influence of the "cage effect" on the mechanism of reversible bimolecular
      multistage chemical reactions in solutions.
AB  - Manifestations of the "cage effect" at the encounters of reactants are
      theoretically treated by the example of multistage reactions in liquid solutions
      including bimolecular exchange reactions as elementary stages. It is shown that
      consistent consideration of quasi-stationary kinetics of multistage reactions
      (possible only in the framework of the encounter theory) for reactions proceeding
      near reactants contact can be made on the basis of the concepts of a "cage
      complex." Though mathematically such a consideration is more complicated, it is
      more clear from the standpoint of chemical notions. It is established that the
      presence of the "cage effect" leads to some important effects not inherent in
      reactions in gases or those in solutions proceeding in the kinetic regime, such
      as the appearance of new transition channels of reactant transformation that
      cannot be caused by elementary event of chemical conversion for the given
      mechanism of reaction. This results in that, for example, rate constant values of
      multistage reaction defined by standard kinetic equations of formal chemical
      kinetics from experimentally measured kinetics can differ essentially from real
      values of these constants. 

PMID- 26298126
TI  - On the use of different coordinate systems in mechanochemical force analyses.
AB  - Force analyses are crucial for a comprehensive understanding of mechanochemical
      processes. The choice of coordinate system in these kinds of analyses is a
      nontrivial task that determines the quality and validity of the obtained results.
      Here, we study the suitability of different sets of coordinates for mechanical
      force analyses, i.e., normal modes, delocalized internal, redundant internal, and
      Z-matrix coordinates. After discussing the theoretical foundations of force
      analyses using different coordinate systems, we investigate a number of test
      molecules. We show that normal modes and Z-matrix coordinates deliver useful
      results only if certain requirements are fulfilled and that only redundant
      internal coordinates yield meaningful results in all cases. 

PMID- 26298128
TI  - Absolute shielding scales for Al, Ga, and In and revised nuclear magnetic dipole
      moments of (27)Al, (69)Ga, (71)Ga, (113)In, and (115)In nuclei.
AB  - We present coupled cluster calculations of NMR shielding constants of aluminum,
      gallium, and indium in water-ion clusters. In addition, relativistic and
      dynamical corrections and the influence of the second solvation shell are
      evaluated. The final NMR shielding constants define new absolute shielding
      scales, 600.0 +/- 4.1 ppm, 2044.4 +/- 31.4 ppm, and 4507.7 +/- 63.7 ppm for
      aluminum, gallium, and indium, respectively. The nuclear magnetic dipole moments
      for (27)Al, (69)Ga, (71)Ga, (113)In, and (115)In isotopes are corrected by
      combining the computed shielding constants with experimental NMR frequencies. The
      absolute magnitude of the correction increases along the series and for indium
      isotopes it reaches approximately -8.0 * 10(-3) of the nuclear magneton. 

PMID- 26298129
TI  - Accurate ab initio-based double many-body expansion potential energy surface for
      the adiabatic ground-state of the C3 radical including combined Jahn-Teller plus
      pseudo-Jahn-Teller interactions.
AB  - A fully ab initio-based potential energy surface is first reported for the ground
      electronic state of the C3 radical using the double many-body expansion (DMBE)
      method. The DMBE form so obtained mimics the full set of energies calculated at
      the multireference configuration interaction level of theory with chemical
      accuracy. To account for the incompleteness of the one- and N-electron bases, the
      calculated external correlation energies have been scaled prior to the fitting
      procedure via DMBE-scaled external correlation method. Furthermore, the novel
      potential energy surface reproduces accurately dissociation energies, diatomic
      potentials, long-range interactions at all asymptotic channels, and the correct
      topological behavior at the region of 4 conical intersections with the partner
      state of the same symmetry near equilateral triangular geometries due to combined
      Jahn-Teller (E' ? e') plus pseudo-Jahn-Teller [(E'+A1')?e'] interactions.
      Rovibrational calculations have also been performed, unveiling a good match of
      the vibrational spectrum of C3 for 53 calculated levels. The present DMBE form
      is, therefore, commended for both spectroscopic and reaction dynamics studies,
      some also performed in the present work.

PMID- 26298127
TI  - Effective doping of low energy ions into superfluid helium droplets.
AB  - We report a facile method of doping cations from an electrospray ionization (ESI)
      source into superfluid helium droplets. By decelerating and stopping the ion
      pulse of reserpine and substance P from an ESI source in the path of the droplet
      beam, about 10(4) ion-doped droplets (one ion per droplet) can be recorded,
      corresponding to a pickup efficiency of nearly 1 out of 1000 ions. We attribute
      the success of this simple approach to the long residence time of the cations in
      the droplet beam. The resulting size of the doped droplets, on the order of
      10(5)/droplet, is measured using deflection and retardation methods. Our method
      does not require an ion trap in the doping region, which significantly simplifies
      the experimental setup and procedure for future spectroscopic and diffraction
      studies. 

PMID- 26298130
TI  - Excited state of protonated benzene and toluene.
AB  - We present photo-fragmentation electronic spectra of the simplest protonated
      aromatic molecules, protonated benzene and toluene, recorded under medium
      resolution conditions and compared with the photo-fragmentation spectrum of
      protonated pyridine. Despite the resolution and cold temperature achieved in the
      experiment, the electronic spectra of protonated benzene and toluene are
      structure-less, thus intrinsically broadened. This is in agreement with the large
      geometrical changes and the fast dynamic toward internal conversion predicted by
      ab initio calculations for protonated benzene [Rode et al., J. Phys. Chem. A 113,
      5865-5873 (2009)]. 

PMID- 26298131
TI  - The spectroscopy and photochemistry of quinioline structural isomers: (E)- and
      (Z)-phenylvinylnitrile.
AB  - In Titan's atmosphere, photochemical pathways that lead to nitrogen
      heteroaromatics may incorporate photoisomerization of their structural isomers as
      a final step. (E)- and (Z)-phenylvinylnitrile ((E)- and (Z)-PVN, C6H5-CH=CHCN)
      are structural isomers of quinoline that themselves possess extensive absorptions
      in the ultraviolet, and thus may engage in such photoisomerization pathways. The
      present study explores the vibronic spectroscopy and photo-induced isomerization
      of gas-phase (E)- and (Z)-PVN in the 33,600-35,850 cm(-1) region under jet-cooled
      conditions. The S0-S1 origins for (E)- and (Z)-PVN have been identified at 33 827
      cm(-1) and 33 707 cm(-1), respectively. Isomer-specific UV-UV hole-burning and UV
      depletion spectra reveal sharp vibronic structure that extends over almost 2000
      cm(-1), with thresholds for fast non-radiative decay identified by a comparison
      between hole-burning and UV depletion spectra. Dispersed fluorescence spectra of
      the two isomers enable the assignment of many low frequency transitions in both
      molecules, aided by harmonic frequency calculations (B3LYP/6-311++G(d,p)) and a
      comparison with the established spectroscopy of phenylvinylacetylene, the ethynyl
      counterpart to PVN. Both isomers are proven to be planar in both the S0 ground
      and S1 electronic excited states. (E)-PVN exhibits extensive Duschinsky mixing
      involving out-of-plane modes whose frequencies and character change significantly
      in the pipi* transition, which modulates the degree of single- and double-bond
      character along the vinylnitrile substituent. This same mixing is much less
      evident in (Z)-PVN. The spectroscopic characterization of (E)- and (Z)-PVN served
      as the basis for photoisomerization experiments using ultraviolet hole-filling
      spectroscopy carried out in a reaction tube affixed to the pulsed valve.
      Successful interconversion between (E) and (Z)-PVN was demonstrated via
      ultraviolet hole-filling experiments. Photoexcitation of (E)- and (Z)-PVN at
      their respective S0-S1 origins failed to produce quinoline, a simple polycyclic
      aromatic nitrogen heterocylcle, within the detection sensitivity of our
      experiments. Stationary points along the potential energy surface associated with
      (Z)-PVN -> quinoline isomerization showed a barrier of 93 kcal/mol associated
      with the first step in the isomerization process, slowing the interconversion
      process at the excitation energies used (96 kcal/mol) to timescales beyond those
      probed in the present experiment.

PMID- 26298132
TI  - Theoretical study of the electronic spectra of neutral and cationic NpO and NpO2.
AB  - The electronic spectra of neutral NpO and NpO2 as well as of their mono- (NpO(+),
      NpO2(+)) and dications (NpO(2+), NpO2(2+)) were studied using
      multiconfigurational relativistic quantum chemical calculations at the complete
      active space self-consistent field/CASPT2 level of theory taking into account
      spin-orbit coupling. The active space included 16 orbitals: all the 7s, 6d, and
      5f orbitals of neptunium together with selected orbitals of oxygen. The vertical
      excitation energies on the ground state geometries have been computed up to ca.
      35,000 cm(-1). The gas-phase electronic spectra were evaluated on the basis of
      the computed Einstein coefficients at 298 K and 3000 K. The computed vertical
      transition energies show good agreement with previous condensed-phase results on
      NpO2(+) and NpO2(2+).

PMID- 26298133
TI  - Fluorinated noble-gas cyanides FKrCN, FXeCN, and FXeNC.
AB  - We report on three new noble-gas molecules, FKrCN, FXeCN, and FXeNC, prepared in
      low-temperature Kr and Xe matrices. These molecules are made by UV photolysis of
      FCN in the matrices and subsequent thermal annealing. The FCN precursor is
      produced by deposition of the matrix gas containing (FCN)3 through a microwave
      discharge. The new noble-gas molecules are assigned with the help of quantum
      chemical calculations at the MP2(full) and CCSD(T) levels of theory. Similar Ar
      compounds (FArCN and FArNC) as well as FKrNC are not found in these experiments,
      which is in agreement with the calculated energetics. 

PMID- 26298134
TI  - Fragmentation of mercury compounds under ultraviolet light irradiation.
AB  - Ultraviolet light induced photofragmentation of mercury compounds is studied
      experimentally with electron energy resolved photoelectron-photoion coincidence
      techniques and theoretically with computational quantum chemical methods. A high
      resolution photoelectron spectrum using synchrotron radiation is presented.
      Fragmentation of the molecule is studied subsequent to ionization to the atomic
      mercury-like d orbitals. State dependent fragmentation behaviour is presented and
      specific reactions for dissociation pathways are given. The fragmentation is
      found to differ distinctly in similar orbitals of different mercury compounds. 

PMID- 26298135
TI  - Simulation of femtosecond two-dimensional electronic spectra of conical
      intersections.
AB  - We have simulated femtosecond two-dimensional (2D) electronic spectra for an
      excited-state conical intersection using the wave-function version of the
      equation-of-motion phase-matching approach. We show that 2D spectra at fixed
      values of the waiting time provide information on the structure of the vibronic
      eigenstates of the conical intersection, while the evolution of the spectra with
      the waiting time reveals predominantly ground-state wave-packet dynamics. The
      results show that 2D spectra of conical intersection systems differ significantly
      from those obtained for chromophores with well separated excited-state potential
      energy surfaces. The spectral signatures which can be attributed to conical
      intersections are discussed. 

PMID- 26298136
TI  - Electron attachment and positive ion chemistry of monohydrogenated fluorocarbon
      radicals.
AB  - Rate coefficients and product branching fractions for electron attachment and for
      reaction with Ar(+) are measured over the temperature range 300-585 K for three
      monohydrogenated fluorocarbon (HFC) radicals (CF3CHF, CHF2CF2, and CF3CHFCF2), as
      well as their five closed-shell precursors (1-HC2F4I, 2-HC2F4I, 2-HC2F4Br, 1
      HC3F6I, 2-HC3F6Br). Attachment to the HFC radicals is always fairly inefficient
      (between 0.1% and 10% of the Vogt-Wannier capture rate), but generally faster
      than attachment to analogous perfluorinated carbon radicals. The primary products
      in all cases are HF-loss to yield C(n)F(m-1)(-) anions, with only a minor
      branching to F(-) product. In all cases the temperature dependences are weak.
      Attachment to the precursor halocarbons is near the capture rate with a slight
      negative temperature dependence in all cases except for 2-HC2F4Br, which is ~10%
      efficient at 300 K and becomes more efficient, approaching the capture rate at
      higher temperatures. All attachment kinetics are successfully reproduced using a
      kinetic modeling approach. Reaction of the HFC radicals with Ar(+) proceeds at or
      near the calculated collisional rate coefficient in all cases, yielding a wide
      variety of product ions.

PMID- 26298137
TI  - Making sense of the conflicting magic numbers in WSi(n) clusters.
AB  - First principles studies on the geometric structure, stability, and electronic
      structure of WSi(n) clusters, n = 6-16, have been carried out to show that the
      observed differing "magic sizes" for WSi(n) clusters are associated with the
      nature of the growth processes. The WSi12 cluster, observed as a magic species in
      experiments reacting transition metal ions with silane, is not stable due to a
      filled shell of 18 electrons, as previously proposed, but due to its atomic
      structure that arrests further growth because of an endohedral transition metal
      site. In fact, it is found that all of these clusters, n = 6-16, have filled 5d
      shells except for WSi12, which has a 5d(8) configuration that is caused by
      crystal field splitting. The stability of WSi15 (+), observed as highly stable in
      clusters generated by vaporizing silicon and metal carbonyls, is shown to be
      associated with a combination of geometric and electronic features. The findings
      are compared with previous results on CrSi(n) clusters.

PMID- 26298138
TI  - "Plug-and-Play" potentials: Investigating quantum effects in (H2)2-Li(+)-benzene.
AB  - Quantum and anharmonic effects are investigated in (H2)2-Li(+)-benzene, a model
      for hydrogen adsorption in metal-organic frameworks and carbon-based materials,
      using rigid-body diffusion Monte Carlo (RBDMC) simulations. The potential-energy
      surface (PES) is calculated as a modified Shepard interpolation of M05-2X/6
      311+G(2df,p) electronic structure data. The RBDMC simulations yield zero-point
      energies (ZPE) and probability density histograms that describe the ground-state
      nuclear wavefunction. Binding a second H2 molecule to the H2-Li(+)-benzene
      complex increases the ZPE of the system by 5.6 kJ mol(-1) to 17.6 kJ mol(-1).
      This ZPE is 42% of the total electronic binding energy of (H2)2-Li(+)-benzene and
      cannot be neglected. Our best estimate of the 0 K binding enthalpy of the second
      H2 to H2-Li(+)-benzene is 7.7 kJ mol(-1), compared to 12.4 kJ mol(-1) for the
      first H2 molecule. Anharmonicity is found to be even more important when a second
      (and subsequent) H2 molecule is adsorbed; use of harmonic ZPEs results in
      significant error in the 0 K binding enthalpy. Probability density histograms
      reveal that the two H2 molecules are found at larger distance from the Li(+) ion
      and are more confined in the theta coordinate than in H2-Li(+)-benzene. They also
      show that both H2 molecules are delocalized in the azimuthal coordinate, phi.
      That is, adding a second H2 molecule is insufficient to localize the wavefunction
      in phi. Two fragment-based (H2)2-Li(+)-benzene PESs are developed. These use a
      modified Shepard interpolation for the Li(+)-benzene and H2-Li(+)-benzene
      fragments, and either modified Shepard interpolation or a cubic spline to model
      the H2-H2 interaction. Because of the neglect of three-body H2, H2, Li(+) terms,
      both fragment PESs lead to overbinding of the second H2 molecule by 1.5 kJ mol(
      1). Probability density histograms, however, indicate that the wavefunctions for
      the two H2 molecules are effectively identical on the "full" and fragment PESs.
      This suggests that the 1.5 kJ mol(-1) error is systematic over the regions of
      configuration space explored by our simulations. Notwithstanding this, modified
      Shepard interpolation of the weak H2-H2 interaction is problematic and we obtain
      more accurate results, at considerably lower computational cost, using a cubic
      spline interpolation. Indeed, the ZPE of the fragment-with-spline PES is
      identical, within error, to the ZPE of the full PES. This fragmentation scheme
      therefore provides an accurate and inexpensive method to study higher hydrogen
      loading in this and similar systems. 

PMID- 26298139
TI  - Pressure-induced transformations in glassy water: A computer simulation study
      using the TIP4P/2005 model.
AB  - We study the pressure-induced transformations between low-density amorphous (LDA)
      and high-density amorphous (HDA) ice by performing out-of-equilibrium molecular
      dynamics (MD) simulations. We employ the TIP4P/2005 water model and show that
      this model reproduces qualitatively the LDA-HDA transformations observed
      experimentally. Specifically, the TIP4P/2005 model reproduces remarkably well the
      (i) structure (OO, OH, and HH radial distribution functions) and (ii) densities
      of LDA and HDA at P = 0.1 MPa and T = 80 K, as well as (iii) the qualitative
      behavior of rho(P) during compression-induced LDA-to-HDA and decompression
      induced HDA-to-LDA transformations. At the rates explored, the HDA-to-LDA
      transformation is less pronounced than in experiments. By studying the LDA-HDA
      transformations for a broad range of compression/decompression temperatures, we
      construct a "P-T phase diagram" for glassy water that is consistent with
      experiments and remarkably similar to that reported previously for ST2 water.
      This phase diagram is not inconsistent with the possibility of TIP4P/2005 water
      exhibiting a liquid-liquid phase transition at low temperatures. A comparison
      with previous MD simulation studies of SPC/E and ST2 water as well as experiments
      indicates that, overall, the TIP4P/2005 model performs better than the SPC/E and
      ST2 models. The effects of cooling and compression rates as well as aging on our
      MD simulations results are also discussed. The MD results are qualitatively
      robust under variations of cooling/compression rates (accessible in simulations)
      and are not affected by aging the hyperquenched glass for at least 1 MUs. A
      byproduct of this work is the calculation of TIP4P/2005 water's diffusion
      coefficient D(T) at P = 0.1 MPa. It is found that, for T >= 210 K, D(T) ~ (T -
      T(MCT))(-gamma) as predicted by mode coupling theory and in agreement with
      experiments. For TIP4P/2005 water, T(MCT) = 209 K and gamma = 2.14, very close to
      the corresponding experimental values T(MCT) = 221 K and gamma = 2.2.

PMID- 26298140
TI  - Structural singularities in Ge(x)Te(100-x) films.
AB  - Structural and calorimetric investigation of Ge(x)Te(100-x) films over wide range
      of concentration 10 < x < 50 led to evidence two structural singularities at x ~
      22 at. % and x ~ 33-35 at. %. Analysis of bond distribution, bond variability,
      and glass thermal stability led to conclude to the origin of the first
      singularity being the flexible/rigid transition proposed in the framework of
      rigidity model and the origin of the second one being the disappearance of the
      undercooled region resulting in amorphous materials with statistical
      distributions of bonds. While the first singularity signs the onset of the Ge-Ge
      homopolar bonds, the second is related to compositions where enhanced Ge-Ge
      correlations at intermediate lengthscales (7.7 A) are observed. These two
      threshold compositions correspond to recently reported resistance drift threshold
      compositions, an important support for models pointing the breaking of homopolar
      Ge-Ge bonds as the main phenomenon behind the ageing of phase change materials.

PMID- 26298141
TI  - Systematic coarse-graining in nucleation theory.
AB  - In this work, we show that the standard method to obtain nucleation rate
      predictions with the aid of atomistic Monte Carlo simulations leads to nucleation
      rate predictions that deviate 3 - 5 orders of magnitude from the recent brute
      force molecular dynamics simulations [Diemand et al., J. Chem. Phys. 139, 074309
      (2013)] conducted in the experimental accessible supersaturation regime for
      Lennard-Jones argon. We argue that this is due to the truncated state space the
      literature mostly relies on, where the number of atoms in a nucleus is considered
      the only relevant order parameter. We here formulate the nonequilibrium
      statistical mechanics of nucleation in an extended state space, where the
      internal energy and momentum of the nuclei are additionally incorporated. We show
      that the extended model explains the lack in agreement between the molecular
      dynamics simulations by Diemand et al. and the truncated state space. We
      demonstrate additional benefits of using the extended state space; in particular,
      the definition of a nucleus temperature arises very naturally and can be shown
      without further approximation to obey the fluctuation law of McGraw and
      LaViolette. In addition, we illustrate that our theory conveniently allows to
      extend existing theories to richer sets of order parameters. 

PMID- 26298142
TI  - Indication of non-thermal contribution to visible femtosecond laser-induced CO
      oxidation on Ru(0001).
AB  - We studied CO oxidation on Ru(0001) induced by 400 nm and 800 nm femtosecond
      laser pulses where we find a branching ratio between CO oxidation and desorption
      of 1:9 and 1:31, respectively, showing higher selectivity towards CO oxidation
      for the shorter wavelength excitation. Activation energies computed with density
      functional theory show discrepancies with values extracted from the experiments,
      indicating both a mixture between different adsorbed phases and importance of non
      adiabatic effects on the effective barrier for oxidation. We simulated the
      reactions using kinetic modeling based on the two-temperature model of laser
      induced energy transfer in the substrate combined with a friction model for the
      coupling to adsorbate vibrations. This model gives an overall good agreement with
      experiment except for the substantial difference in yield ratio between CO
      oxidation and desorption at 400 nm and 800 nm. However, including also the
      initial, non-thermal effect of electrons transiently excited into antibonding
      states of the O-Ru bond yielded good agreement with all experimental results. 

PMID- 26298143
TI  - Proton transport in ice at 30-140 K: Effects of porosity.
AB  - We examined the role of porosity, a crucial characteristic of amorphous solid
      water (ASW), on electrostatic charging and discharging of ASW films with 500 eV
      He(+) and Xe(+) ions, by measuring the surface potentials with a Kelvin probe.
      When a charged ASW film is heated, its surface potential decreases sharply, at
      temperatures that depend on the maximum temperature the film was once subject to.
      This sharp decrease of the surface potential is not due to a large thermally
      induced increase of the dielectric constant epsilon as proposed in other studies,
      since measurements of epsilon yielded a value of ~3 below ~100 K. Rather, the
      potential drop can be explained by the transport of the surface charge to the
      substrate, which depends on film porosity. We propose that the charge migrates
      along the walls of the pores within the ASW film, facilitated by the thermally
      induced reorientation of the incompletely coordinated molecules on the pore
      walls. 

PMID- 26298144
TI  - Super-radiant plasmon mode is more efficient for SERS than the sub-radiant mode
      in highly packed 2D gold nanocube arrays.
AB  - The field coupling in highly packed plasmonic nanoparticle arrays is not
      localized due to the energy transport via the sub-radiant plasmon modes, which is
      formed in addition to the regular super-radiant plasmon mode. Unlike the sub
      radiant mode, the plasmon field of the super-radiant mode cannot extend over long
      distances since it decays radiatively with a shorter lifetime. The coupling of
      the plasmon fields of gold nanocubes (AuNCs) when organized into highly packed 2D
      arrays was examined experimentally. Multiple plasmon resonance optical peaks are
      observed for the AuNC arrays and are compared to those calculated using the
      discrete dipole approximation. The calculated electromagnetic plasmon fields of
      the arrays displayed high field intensity for the nanocubes located in the center
      of the arrays for the lower energy super-radiant mode, while the higher energy
      sub-radiant plasmon mode displayed high field intensity at the edges of the
      arrays. The Raman signal enhancement by the super-radiant plasmon mode was found
      to be one hundred fold greater than that by sub-radiant plasmon mode because the
      super-radiant mode has higher scattering and stronger plasmon field intensity
      relative to the sub-radiant mode. 

PMID- 26298145
TI  - Structure and dynamics of a layer of sedimented particles.
AB  - We investigate experimentally and theoretically thin layers of colloid particles
      held adjacent to a solid substrate by gravity. Epifluorescence, confocal, and
      holographic microscopy, combined with Monte Carlo and hydrodynamic simulations,
      are applied to infer the height distribution function of particles above the
      surface, and their diffusion coefficient parallel to it. As the particle area
      fraction is increased, the height distribution becomes bimodal, indicating the
      formation of a distinct second layer. In our theory, we treat the suspension as a
      series of weakly coupled quasi-two-dimensional layers in equilibrium with respect
      to particle exchange. We experimentally, numerically, and theoretically study the
      changing occupancies of the layers as the area fraction is increased. The
      decrease of the particle diffusion coefficient with concentration is found to be
      weakened by the layering. We demonstrate that particle polydispersity strongly
      affects the properties of the sedimented layer, because of particle size
      segregation due to gravity. 

PMID- 26298146
TI  - The atomic structure of low-index surfaces of the intermetallic compound InPd.
AB  - The intermetallic compound InPd (CsCl type of crystal structure with a broad
      compositional range) is considered as a candidate catalyst for the steam
      reforming of methanol. Single crystals of this phase have been grown to study the
      structure of its three low-index surfaces under ultra-high vacuum conditions,
      using low energy electron diffraction (LEED), X-ray photoemission spectroscopy
      (XPS), and scanning tunneling microscopy (STM). During surface preparation,
      preferential sputtering leads to a depletion of In within the top few layers for
      all three surfaces. The near-surface regions remain slightly Pd-rich until
      annealing to ~580 K. A transition occurs between 580 and 660 K where In
      segregates towards the surface and the near-surface regions become slightly In
      rich above ~660 K. This transition is accompanied by a sharpening of LEED
      patterns and formation of flat step-terrace morphology, as observed by STM.
      Several superstructures have been identified for the different surfaces
      associated with this process. Annealing to higher temperatures (>=750 K) leads to
      faceting via thermal etching as shown for the (110) surface, with a bulk In
      composition close to the In-rich limit of the existence domain of the cubic
      phase. The Pd-rich InPd(111) is found to be consistent with a Pd-terminated bulk
      truncation model as shown by dynamical LEED analysis while, after annealing at
      higher temperature, the In-rich InPd(111) is consistent with an In-terminated
      bulk truncation, in agreement with density functional theory (DFT) calculations
      of the relative surface energies. More complex surface structures are observed
      for the (100) surface. Additionally, individual grains of a polycrystalline
      sample are characterized by micro-spot XPS and LEED as well as low-energy
      electron microscopy. Results from both individual grains and "global"
      measurements are interpreted based on comparison to our single crystals findings,
      DFT calculations and previous literature. 

PMID- 26298147
TI  - Non-ideal diffusion effects, short-range ordering, and unsteady-state effects
      strongly influence Brownian aggregation rates in concentrated dispersions of
      interacting spheres.
AB  - Brownian aggregation rates are determined for concentrated dispersions of
      interacting particles with Brownian dynamics (BD) simulations and various
      theoretical models. Using simulation results as benchmarks, the predictions of
      the classical Fuchs-Smoluchowski (FS) model are shown to be quite inaccurate for
      concentrated dispersions. A new aggregation model is presented which provides
      significantly improved predictions. This model is developed on the basis of the
      fundamental measure theory (FMT) which is a rigorous "liquid-state" dynamic
      density-functional theory (DDFT) approach. It provides a major improvement of the
      FS model by considering short-range ordering, non-ideal diffusion, and unsteady
      state effects. These were recently shown by the authors to play important roles
      in Brownian aggregation of hard spheres at high concentrations. Two types of
      interparticle interaction potentials are examined, the purely attractive van der
      Waals potential and the DLVO potential which includes van der Waals attraction
      and electrostatic double layer repulsion. For dispersions of particles with
      purely attractive interactions, the FS model underpredicts the aggregation rates
      by up to 1000 fold. In the presence of strong interparticle repulsive forces, its
      predictions are in fair agreement with the BD simulation results for dilute
      systems with particle volume fractions phi < < 0.1. In contrast, the predictions
      of the new FM-DDFT based model compare favorably with the BD simulation results,
      in both cases, up to phi = 0.3. A new quantitative measure for colloidal
      dispersion stability, different from the classical FS stability ratio, is
      proposed on the basis of aggregation half-times. Hence, a better mechanistic
      understanding of Brownian aggregation is obtained for concentrated dispersions of
      particles with either attractive or repulsive interactions, or both. 

PMID- 26298148
TI  - Incommensurate superstructure in heavily doped fullerene layer on Bi/Si(111)
      surface.
AB  - Cs adsorption onto the C60-covered Si(111)-beta-?3*?3-Bi reconstruction has been
      studied by means of scanning tunneling microscopy and photoelectron spectroscopy.
      Unexpected increase in apparent size of every second C60 molecule has been
      detected, hereupon the close packed molecular array almost doubles its
      periodicity. The change affects only the fullerenes that are in direct contact
      with the metal-induced reconstruction and takes no place already in the second
      layer. Photoelectron studies have revealed that this incommensurate "2 * 2"
      superstructure of a heavily doped C60 monolayer remains in an insulating state
      regardless of doping level.

PMID- 26298149
TI  - Growth and structure of ultrathin cerium oxide films on Rh(111).
AB  - The geometric structure of ultra-thin cerium oxide films on Rh(111), prepared by
      annealing the metallic cerium films at a very low coverage between 0.3 and 1.5
      monolayers in an oxygen atmosphere, is investigated using scanning tunneling
      microscopy (STM), low-energy electron diffraction (LEED), X-ray photoelectron
      spectroscopy, and density functional theory (DFT) calculations. The STM image and
      LEED pattern indicate that cerium oxide films epitaxially grown as ordered
      CeO2(111) layers aligned to the 110 azimuthal direction of Rh(111). The in-plane
      lattice parameter measured from the LEED pattern appears to be contracted with
      respect to the bulk ceria lattice. The measured ratio Ce:O for two-trilayer
      cerium oxide film is 1.96:1, which is close to the stoichiometric ratio. The
      simulated STM image on the basis of DFT+U calculations is in good agreement with
      the experimental STM images. 

PMID- 26298150
TI  - Coarsening mechanics of a colloidal suspension in toggled fields.
AB  - Suspensions of paramagnetic colloids are driven to phase separate and self
      assemble in toggled magnetic fields. At field strengths above 575 A/m and toggle
      frequencies between 0.66 and 2 Hz, an initial gel-like, arrested network
      collapses into condensed, ellipsoidal aggregates. The evolution to this
      equilibrium structure occurs via a Rayleigh-Plateau instability. The toggle
      frequency nu determines the fluidity of the breakup process. At frequencies
      between 0.66 and 1.5 Hz, the suspension breaks up similar to a viscous, Newtonian
      fluid. At frequencies nu > 1.5 Hz, the network ruptures like a viscoplastic
      material. The field strength alters the onset time of the instability. A power
      law relationship emerges as the scaled frequency and field strength can be used
      to predict the onset of breakup. These results further aid in understanding the
      mechanics and dynamics of the phase separation process of suspensions of
      polarizable colloids in toggled external fields. 

PMID- 26298151
TI  - On the mesoscopic origins of high viscosities in some polyelectrolyte-surfactant
      mixtures.
AB  - Oppositely charged polyelectrolyte (PE) surfactant mixtures allow the control of
      rheological parameters of a solution even at fairly low concentrations. For
      example, addition of 0.3 wt. % of anionic surfactant to a 1 wt. % solution of the
      polycation JR 400 increases the viscosity by 4 orders of magnitude. Recently, we
      could show that this increase is related to the formation of mixed, rod-like
      PE/surfactant aggregates which interconnect several polyelectrolyte chains
      [Hoffmann et al., Europhys. Lett. 104, 28001 (2013)]. In this paper, we refine
      our structural model of the aggregates to obtain a more consistent picture of
      their internal structure for different anionic surfactants. Combining small angle
      neutron scattering (SANS) and neutron spin-echo (NSE) allows us to determine the
      size of the aggregates. By comparing different contrasts, the internal structure
      of the aggregates can be elucidated and it is seen that the PE in the aggregates
      retains a relatively high freedom of movement. We proceeded to investigate the
      influence of the surfactant concentration and the surfactant type on structure
      and dynamics of the mixed aggregates. It is seen that the structural parameters
      of the aggregates depend very little on the surfactant concentration and
      headgroup. However, it is crucial to incorporate a sufficient amount of PE in the
      aggregates to increase the viscosity of the aggregates. By comparing viscous
      samples at 1 wt. % PE concentration with samples at a PE concentration of 0.3 wt.
      %, where no significant increase in viscosity is observed, we find that similar
      aggregates are formed already at this lower PE concentrations. However, the
      amount of PE incorporated in them is insufficient to interconnect several PE
      chains and therefore, they do not increase viscosity. So, our detailed
      investigation combining contrast variation SANS and NSE does not only allow to
      explain the viscosity behavior but also to deduced detailed information regarding
      the structures and the dynamics especially of the polyelectrolyte within the
      complexes. 

PMID- 26298152
TI  - Thermal diffusivity anisotropy measured by a temperature wave method in the
      homologous series of (p-alkoxybenzylidene)-p'-octylaniline (nO.8).
AB  - The anisotropy of thermal diffusivity in four homologues of (p-alkoxybenzylidene)
      p'-octylaniline (nO.8, n = 4 - 7) was measured using a temperature wave method.
      The results show that the thermal diffusivity component along the director
      (alpha(?)) is considerably larger than that perpendicular to the director
      (alpha(?)) in all mesophases, i.e., nematic (N), smectic A (SmA), smectic B
      (SmB), and smectic G (SmG) phases. Both components of the thermal diffusivity
      show a dip at the second- or weakly first-order N-SmA phase transition due to the
      heat capacity anomaly. In contrast, at the first-order SmA-SmB phase transition,
      thermal diffusivity exhibits a stepwise increase. The x-ray and calorimetric
      measurements enable a calculation of the thermal conductivity and the study of
      the effect of the molecular length on the thermal conductivity and diffusivity in
      the SmA and SmB phases. For the homologues n = 4, 5, and 6, which exhibit the
      same phase sequence upon cooling, the parallel component of the thermal
      conductivity k(?) in the SmA and SmB phases systematically increases with
      increasing length of the molecular tails, while no such increase is observed in
      the thermal diffusivity alpha(?). We thus conclude that the molecular model
      [Urbach et al., J. Chem. Phys. 78, 5113 (1983)] is valid for the qualitative
      prediction of the effect of the molecular length on the magnitude of the thermal
      conductivity.

PMID- 26298153
TI  - Improving the prospects of cleavage-based nanopore sequencing engines.
AB  - Recently proposed methods for DNA sequencing involve the use of cleavage-based
      enzymes attached to the opening of a nanopore. The idea is that DNA interacting
      with either an exonuclease or polymerase protein will lead to a small molecule
      being cleaved near the mouth of the nanopore, and subsequent entry into the pore
      will yield information about the DNA sequence. The prospects for this approach
      seem promising, but it has been shown that diffusion related effects impose a
      limit on the capture probability of molecules by the pore, which limits the
      efficacy of the technique. Here, we revisit the problem with the goal of
      optimizing the capture probability via a step decrease in the nucleotide
      diffusion coefficient between the pore and bulk solutions. It is shown through
      random walk simulations and a simplified analytical model that decreasing the
      molecule's diffusion coefficient in the bulk relative to its value in the pore
      increases the nucleotide capture probability. Specifically, we show that at
      sufficiently high applied transmembrane potentials (>=100 mV), increasing the
      potential by a factor f is equivalent to decreasing the diffusion coefficient
      ratio D(bulk)/D(pore) by the same factor f. This suggests a promising route
      toward implementation of cleavage-based sequencing protocols. We also discuss the
      feasibility of forming a step function in the diffusion coefficient across the
      pore-bulk interface.

PMID- 26298154
TI  - Theory of polymer translocation through a flickering nanopore under an
      alternating driving force.
AB  - We develop a theory for polymer translocation driven by a time-dependent force
      through an oscillating nanopore. To this end, we extend the iso-flux tension
      propagation theory [Sarabadani et al., J. Chem. Phys. 141, 214907 (2014)] for
      such a setup. We assume that the external driving force in the pore has a
      component oscillating in time, and the flickering pore is similarly described by
      an oscillating term in the pore friction. In addition to numerically solving the
      model, we derive analytical approximations that are in good agreement with the
      numerical simulations. Our results show that by controlling either the force or
      pore oscillations, the translocation process can be either sped up or slowed down
      depending on the frequency of the oscillations and the characteristic time scale
      of the process. We also show that while in the low and high frequency limits, the
      translocation time tau follows the established scaling relation with respect to
      chain length N0, in the intermediate frequency regime small periodic,
      fluctuations can have drastic effects on the dynamical scaling. The results can
      be easily generalized for non-periodic oscillations and elucidate the role of
      time dependent forces and pore oscillations in driven polymer translocation. 

PMID- 26298155
TI  - A coarse-grained molecular dynamics study of segmental structure and mobility in
      capped crosslinked copolymer films.
AB  - We present results from molecular-dynamics simulations of a generic bead-spring
      model of copolymer chains confined between solid walls and report on the glass
      transition temperature and segmental dynamics as a function of film thickness and
      mesh size (the end-to-end distance of the subchains in the crosslinked polymer
      networks). Apparently, the glass-transition temperature displayed a steep
      increase for mesh-size values much smaller than the radius of gyration of the
      bulk chains, otherwise it remained invariant to mesh-size variations. The rise in
      the glass-transition temperature with decreasing mesh size and film thickness was
      accompanied by a monotonic slowing-down of segmental dynamics on all studied
      length scales. This observation is attributed to the correspondingly decreased
      width of the bulk density layer that was obtained in films whose thickness was
      larger than the end-to-end distance of the bulk polymer chains. To test this
      hypothesis, additional simulations were performed in which the crystalline walls
      were replaced with amorphous or rough walls. In the amorphous case, the high
      polymer density close to the walls vanished, but the dynamic response of the film
      was not affected. The rough walls, on the other hand, only slightly decreased the
      density close to the walls and led to a minor slowing-down in the dynamics at
      large length-scales. 

PMID- 26298156
TI  - Fast internal dynamics in alcohol dehydrogenase.
AB  - Large-scale domain motions in alcohol dehydrogenase (ADH) have been observed
      previously by neutron spin-echo spectroscopy (NSE). We have extended the
      investigation on the dynamics of ADH in solution by using high-resolution neutron
      time-of-flight (TOF) and neutron backscattering (BS) spectroscopy in the
      incoherent scattering range. The observed hydrogen dynamics were interpreted in
      terms of three mobility classes, which allowed a simultaneous description of the
      measured TOF and BS spectra. In addition to the slow global protein diffusion and
      domain motions observed by NSE, a fast internal process could be identified.
      Around one third of the protons in ADH participate in the fast localized
      diffusive motion. The diffusion coefficient of the fast internal motions is
      around two third of the value of the surrounding D2O solvent. It is tempting to
      associate the fast internal process with solvent exposed amino acid residues with
      dangling side chains. 

PMID- 26298157
TI  - 4E-BP1 as an oncotarget.

PMID- 26298158
TI  - Veiled EGM Jackpots: The Effects of Hidden and Mystery Jackpots on Gambling
      Intensity.
AB  - Understanding the impact of EGM Jackpots on gambling intensity may allow targeted
      strategies to be implemented that facilitate harm minimisation by acting to
      reduce losses of gamblers who play frequently, while maintaining the enjoyment
      and excitement of potential jackpots. The current study investigated the
      influences of Hidden and Mystery Jackpots on EGM gambling intensity. In a Hidden
      Jackpot, the prize value is not shown to the player, although the existence of a
      jackpot prize is advertised. In a Mystery Jackpot, the jackpot triggering state
      of the machine is unknown to players. One hundred and seven volunteers (males =
      49, females = 58) played a laptop-simulated EGM with a starting $20 real-money
      stake and a chance to win a Jackpot ($500). Participants played for either a
      Hidden or Known Jackpot Value, with either a Mystery or Known winning symbol
      combination in a crossed design. Lastly, a control condition with no jackpot was
      included. Gambling intensity (speed of bets, persistence) was greater when the
      Jackpot value was unknown, especially when a winning-symbol combination suggested
      that a win was possible. While there is no evidence in the present investigation
      to suggest that Hidden or Mystery jackpots contribute to greater player
      enjoyment, there is some evidence to suggest a marginal positive contribution of
      hidden jackpots to risky playing behaviour. 

PMID- 26298160
TI  - Is 3-D gait analysis essential? By Professor James Wright: Introduction by Mr.
      Tim Theologis.

PMID- 26298159
TI  - Dual task interference during walking: The effects of texting on situational
      awareness and gait stability.
AB  - Dual-task interference caused by mobile phone use while walking increases safety
      risks by increasing attentional and cognitive demands. Situational awareness,
      important for control of walking and safety, has been examined previously but
      measured only by the awareness of visually noteworthy objects in the environment
      or the number of times the person looked up from the phone. This study
      systematically investigated the effects of texting on situational awareness to
      different environments and its consequent impact on gait kinematics. Twenty
      healthy volunteers walked on a treadmill while texting and attending to visual
      tasks simultaneously. Gait parameters and situational awareness examined under
      dual-task conditions (walk and text or walk, text, and visual task) were compared
      with those of single-task conditions (text, walk or visual task only). The size
      of the visual field, display duration of the visual cue, and visual acuity demand
      were varied across the visual task conditions. About half of the visual cues
      provided during walking and texting were not perceived (48.3%) as compared to the
      visual task only condition. The magnitude of this loss of situational awareness
      was dependent upon the nature of visual information provided. While gait
      parameters were not different among visual task conditions, greater total medial
      lateral excursion of the pelvis was observed in the walk and text condition
      compared to the walk only condition, showing the dual-task effects of texting on
      gait kinematics. The study provides further evidence of dual-task effects of
      texting on situational awareness as well as gait kinematics. 

PMID- 26298162
TI  - Imaging in pleural mesothelioma: A review of the 12th International Conference of
      the International Mesothelioma Interest Group.
AB  - Imaging of malignant pleural mesothelioma is essential to patient management,
      prognostication, and response assessment. From animal models to clinical trials,
      the gamut of research activities and clinical standards relies on imaging to
      provide information on lesion morphology and the growing number of physiologic
      characteristics amenable to capture through imaging techniques. The complex
      morphology, growth pattern, and biological mechanisms of mesothelioma, however,
      present challenges for image acquisition and interpretation. Nevertheless, novel
      approaches to image acquisition and subsequent image analysis have expanded the
      opportunities for (as well as the need for) imaging in this disease. This paper
      summarizes the imaging-based research presented orally at the 2014 International
      Conference of the International Mesothelioma Interest Group (iMig) in Cape Town,
      South Africa, October 2014. Presented topics include the imaging of hypoxia in a
      murine model through positron emission tomography (PET), the use of diffusion
      weighted magnetic resonance imaging (MRI) to assess the histologic composition of
      biphasic mesothelioma and to assess early response to chemotherapy, the
      correlation of CT-based tumor volume with the volume of the post-surgical tumor
      specimen, the development of volumetric tumor response criteria, and pre
      treatment tumor volume growth considerations for tumor response assessment. 

PMID- 26298161
TI  - NZ suppresses TLR4/NF-kappaB signalings and NLRP3 inflammasome activation in LPS
      induced RAW264.7 macrophages.
AB  - OBJECTIVE: The purpose of the present study was to evaluate the potential
      therapeutic effects of NZ on lipopolysaccharide (LPS)-induced RAW264.7 cells and
      explore its underlying mechanisms. METHODS: The effect of NZ on NO generation in
      LPS-activated macrophage was measured by Griess assay. The concentrations of TNF
      alpha, IL-18, IL-1beta were analyzed with ELISA kits. The LPS-induced production
      of reactive oxygen species (ROS) was determined by flow cytometry. The protein
      expressions of TLR4, NF-kappaB and NLRP3 signaling pathway were investigated with
      Western blot analysis. RESULTS: It was shown that NZ significantly reduced the
      production of NO and the generation of pro-inflammatory cytokines in LPS-induced
      RAW264.7 cells. In addition, NZ markedly inhibited the up-regulation of toll-like
      receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and the activation
      of nuclear factor kappa B (NF-kappaB) in LPS-stimulated RAW 264.7 macrophages. Of
      note, NZ suppressed the expression of the inflammasome component such as NOD-like
      receptor 3(NLRP3), apoptosis-associated speck-like protein containing CARD(ASC),
      as well as the levels of cytokines including Interleukin-18(IL-18) and
      Interleukin-1beta(IL-1beta). CONCLUSION: These results indicated that NZ
      inhibited the generations of NO and pro-inflammatory cytokines by suppressing
      TLR4/MyD88/NF-kappaB pathway, suggesting that NZ could be an effective candidate
      for ameliorating LPS-induced inflammatory responses.

PMID- 26298163
TI  - Intraoperative Periprosthetic Fractures in Proximal Interphalangeal Joint
      Arthroplasty.
AB  - PURPOSE: To examine the frequency, risk factors, and postoperative outcomes
      associated with intraoperative periprosthetic fractures during proximal
      interphalangeal (PIP) joint arthroplasty. METHODS: We examined 382 consecutive
      PIP joint arthroplasties in 205 patients. Procedures were performed from 1998 to
      2012. The patients were identified and outcomes were collected through a single
      institution's total joints registry, collecting additional information not
      contained in the prospectively collected registry through medical record
      examination. Multiple outcomes were analyzed relating to the fractures, the hard
      surgical outcomes, finger function, and radiographic findings. Statistical
      analysis was performed utilizing Kaplan-Meier survival models, log-rank tests,
      univariate analysis, Student t test and Fisher exact test. RESULTS:
      Intraoperative periprosthetic fracture occurred in 5% (n = 20) of 383 PIP joint
      arthroplasties. All of the patients who had an intraoperative fracture were
      women. Lower body mass index and a diagnosis of rheumatoid arthritis were
      associated with a significantly higher risk of intraoperative fracture. The use
      of pyrocarbon implants also significantly increased fracture risk. At a median
      follow-up of 5.3 years, there were no refractures in the patients who sustained
      an intraoperative fracture. Six patients underwent revision surgery, with a 2-
      and 5-year survival rate free of revision surgery of 76% and 64%, respectively.
      These rates were not significantly different from those without intraoperative
      fractures. There was no significant difference in the incidence of postoperative
      complications between patients with or without an intraoperative fracture.
      CONCLUSIONS: Intraoperative fractures occur in about 5% of PIP joint
      arthroplasties. These periprosthetic fractures do not appear to influence
      outcomes, including revision surgery, refracture rate, or other early
      complications. Female sex, lower body mass index, rheumatoid arthritis, and the
      use of pyrocarbon implants were associated with increased risk for intraoperative
      fractures. CLINICAL RELEVANCE: This information may help decrease fracture risk
      and help surgeons identify and treat the fractures when they do occur. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Prognostic II.

PMID- 26298164
TI  - Pulmonary Metastases Exhibit Epigenetic Clonality: Implications for Precision
      Cancer Therapy.
AB  - BACKGROUND: Development of effective cancer therapies may be limited by
      intratumoral heterogeneity, which facilitates outgrowth and organ-specific
      dissemination of treatment resistant clones. At present, limited information is
      available regarding epigenetic landscapes of pulmonary metastases. This study was
      undertaken to characterize epigenetic signatures of pulmonary metastases and to
      identify potential therapeutic targets. METHODS: RNA and DNA were extracted from
      65 pulmonary metastases resected from 12 patients (5 with sarcoma, 7 with
      adrenocortical carcinoma). Quantitative reverse transcription polymerase chain
      reaction techniques were used to evaluate expression levels of cancer-testis (CT)
      genes (NY-ESO-1, MAGE-A3, MAGE-A9, MAGE-A12, GAGE1, CT-45, SSX-1, and SSX-2),
      tumor suppressor (TS) genes (p16 and RASSF1A), and genes encoding epigenetic
      modifiers (DNMT1, DNMT3A, DNMT3B, EZH2, EED, and SUZ12), aberrantly expressed in
      human malignant diseases. Pyrosequencing techniques were used to quantitate DNA
      methylation levels in LINE1, NBL2, and D4Z4 repetitive sequences and promoter
      methylation status of differentially regulated genes. Results of these analyses
      were compared with a standardized panel of normal lung tissues. RESULTS:
      Pulmonary metastases exhibited histologically related and patient-specific global
      DNA demethylation. Significant interpatient heterogeneity of gene expression was
      observed even among patients with similar tumor histologic features. Epigenetic
      signatures appeared consistent among metastases from the same patient,
      irrespective of the time of resection (synchronous/metachronous) or the anatomic
      location. EZH2, EED, and SUZ12 (core components of Polycomb repressive complex-2
      [PRC-2]) were upregulated in the majority of metastases. CONCLUSIONS: Pulmonary
      metastases exhibit patient-specific epigenetic clonality, which may be exploited
      for precision therapies targeting aberrant CT or TS gene expression. PRC-2 may be
      a shared target for epigenetic therapy of pulmonary metastases.

PMID- 26298165
TI  - Impact of Lepidic Component Occupancy on Effects of Adjuvant Chemotherapy for
      Lung Adenocarcinoma.
AB  - BACKGROUND: The prognosis of lepidic predominant lung adenocarcinoma is
      favorable. We postulated that lepidic predominant tumors might not require
      postoperative adjuvant chemotherapy. The present study aims to determine whether
      lepidic component occupancy affects overall survival after postoperative adjuvant
      chemotherapy for lung adenocarcinoma. METHODS: Clinical and pathologic data were
      collected from a database and from the medical records of 964 patients with
      completely resected lung adenocarcinoma. We assessed the influence of lepidic
      component occupancy in the tumor on the outcomes of adjuvant chemotherapy.
      RESULTS: Among the patients, 270 received adjuvant chemotherapy and 694 did not,
      and 415 and 549 had lepidic predominant and non-lepidic predominant tumors,
      respectively. Adjuvant chemotherapy contributed to better overall survival
      compared with observation in non-lepidic predominant tumors (p = 0.025).
      Multivariate analyses revealed age, sex, stage, lepidic component occupancy, and
      adjuvant chemotherapy as independent prognostic factors for overall survival. The
      overall survival was significantly longer for patients with non-lepidic
      predominant tumors at stages IA, IB, and II-III under adjuvant chemotherapy
      compared with observation (p = 0.040, p = 0.007, and p = 0.012, respectively),
      whereas survival rates were similar for patients with all stages of lepidic
      predominant tumors even after propensity score matching study. CONCLUSIONS:
      Lepidic component occupancy reflected the effect of adjuvant chemotherapy for
      lung adenocarcinoma. Adjuvant chemotherapy did not have much impact for lepidic
      predominant tumors and could be considered for non-lepidic predominant tumors
      even at stage IA.

PMID- 26298166
TI  - Superior Vena Cava Reconstruction for Treatment of Chylothorax Resulting From
      Thrombosis of Superior Vena Cava in Young Infants.
AB  - BACKGROUND: Thrombosis and occlusion of the superior vena cava (SVC) can cause
      massive chylothorax resulting in significant morbidity and mortality among young
      infants. Medical therapy is often unsuccessful. We report a new surgical
      technique that entails open thrombectomy and reconstruction of the SVC and
      innominate vein to treat this condition. METHODS: The charts of 4 consecutive
      infants with chylothoraces refractory to conservative management were reviewed.
      The operations were performed on cardiopulmonary bypass without myocardial
      arrest. The SVC and innominate veins were incised open, and thrombectomy was
      performed. This was followed by homograft patch reconstruction of both the veins.
      RESULTS: The infants were aged between 5 weeks to 4 months and had an average
      weight of 4 kg. All of them had hypoalbuminemia and evidence of hypercoagulable
      state. After surgical intervention, 3 had complete relief of SVC obstruction. Two
      of the 3 patients had complete resolution of chylous effusion, and the third
      patient had a significant decrease in chest tube drainage (70%) by the end of 1
      week. The fourth patient had recurrence of high drainage after an initial
      improvement, and a subsequent angiogram demonstrated stenosis of the SVC without
      thrombosis. The chest tube drainage finally resolved after balloon angioplasty.
      CONCLUSIONS: Thrombotic occlusion of the SVC can result in chylothorax that is
      often not amenable to medical therapy. This is associated with significant loss
      of proteins and hypercoagulable state. A complete surgical relief of SVC
      obstruction by open thrombectomy and venoplasty can result in dramatic decrease
      in chylous output.

PMID- 26298167
TI  - The Effect of Institutional Volume on Complications and Their Impact on Mortality
      After Pediatric Heart Transplantation.
AB  - BACKGROUND: This study evaluated the potential association of institutional
      volume with survival and mortality subsequent to major complications in a modern
      cohort of pediatric patients after orthotopic heart transplantation (OHT).
      METHODS: The United Network of Organ Sharing database was queried for pediatric
      patients (aged <=18 years) undergoing OHT between 2000 and 2010. Institutional
      volume was defined as the average number of transplants completed annually during
      each institution's active period and was evaluated as categoric and as a
      continuous variable. Logistic regression models were used to determine the effect
      of institutional volumes on postoperative outcomes, which included renal failure,
      stroke, rejection, reoperation, infection, and a composite complication outcome.
      Cox modeling was used to analyze the risk-adjusted effect of institutional volume
      on 30-day, 1-year, and 5-year mortality. Kaplan-Meier estimates were used to
      compare differences in unconditional survival. RESULTS: A total of 3,562 patients
      (111 institutions) were included and stratified into low-volume (<6.5
      transplants/year, 91 institutions), intermediate-volume (6.5 to 12.5
      transplants/year, 12 institutions), and high-volume (>12.5 transplants/year, 8
      institutions) tertiles. Unadjusted survival was significantly different at 30
      days (p = 0.0087) in the low-volume tertile (94.2%; 95% confidence interval,
      92.7% to 95.4%) compared with the high-volume tertile (96.8%; 95% confidence
      interval, 95.7% to 97.7%). No difference was observed at 1 or 5 years. Risk
      adjusted Cox modeling demonstrated that low-volume institutions had an increased
      rate of mortality at 30 days (hazard ratio, 1.91; 95% confidence interval, 1.02
      to 3.59; p = 0.044), but not at 1 or 5 years. High-volume institutions had lower
      incidences of postoperative complications than low-volume institutions (30.3% vs
      38.4%, p < 0.001). Despite this difference in the rate of complications, survival
      in patients with a postoperative complication was similar across the volume
      tertiles. CONCLUSIONS: No association was observed between institutional volume
      and adjusted or unadjusted long-term survival. High-volume institutions have a
      significantly lower rate of postoperative complications after pediatric OHT. This
      association does not correlate with increased subsequent mortality in low-volume
      institutions. Given these findings, strategies integral to the allocation of
      allografts in adult transplantation, such as regionalization of care, may not be
      as relevant to pediatric OHT.

PMID- 26298168
TI  - Triptolide Inhibits Lung Cancer Cell Migration, Invasion, and Metastasis.
AB  - BACKGROUND: Triptolide is an extract from Tripterygium wilfordii used in
      traditional Chinese medicine to treat autoimmune disorders. Triptolide has
      anticancer effects in vitro and is reported to impair cancer cell migration. We
      studied whether triptolide inhibits lung cancer cell migration and metastasis.
      METHODS: We determined the microRNA expression profile of triptolide-treated
      cells. We tested the effects of triptolide treatment on migration and invasion of
      lung cancer cells by using Transwell filters coated with fibronectin and
      Matrigel, respectively. Western blot analyses were used to compare expression of
      proteins involved in cell migration before and after 10 nmol/L triptolide
      treatment. Tail vein injections with H358 cells were performed. The mice were
      treated with 1 mg/kg triptolide or vehicle by intraperitoneal injection three
      times per week. Lung and liver metastases were compared at 9 weeks. Means of
      groups were compared by using a t test. RESULTS: Triptolide altered the
      expression of microRNAs involved in cellular movement and significantly decreased
      migration and invasion of lung cancer cells from approximately 18 to 3 cells per
      field (p < 0.001). Triptolide decreases focal adhesion kinase expression, which
      leads to impairment of downstream signaling. Finally, triptolide-treated mice
      injected with lung cancer cells significantly decreased metastatic colony
      formation in the lungs (p < 0.01). CONCLUSIONS: Triptolide decreases lung cancer
      cell migration and invasion in vitro and inhibits metastatic tumor formation in
      mice. Triptolide suppresses focal adhesion kinase, which causes deregulation of
      the migration machinery. These results suggest that triptolide inhibits lung
      cancer metastasis and should be investigated as a new lung cancer therapy.

PMID- 26298169
TI  - Resected Lung Cancer Patients Who Would and Would Not Have Met Screening
      Criteria.
AB  - BACKGROUND: Current eligibility criteria for lung cancer screening may
      underestimate the risk of malignancy for some individuals. We compared the
      predicted risk of lung cancer among patients who would have met screening
      criteria to those who would not have despite being at moderate-risk. METHODS: A
      retrospective cohort study of resected lung cancer patients was performed. The
      screen eligible group was based on criteria provided by the United States
      Preventive Services Task Force; age 55 to 80 and a 30 or greater pack-year
      smoking history. The screen ineligible group was based on criteria provided by
      the National Comprehensive Cancer Network for a moderate-risk individual not
      recommended screening; age greater than 50 years, greater than 20 pack-year
      smoking history, and no history of asbestos exposure or chronic obstructive
      pulmonary disease. A recently validated risk-prediction model was used to compare
      the risk of lung cancer across eligibility groups based on measured and imputed
      patient-level variables. RESULTS: Screen ineligible patients (n = 88) had a lower
      estimated probability of lung cancer than screen eligible patients (n = 419);
      1.3% versus 3.1%, p value less than 0.001. However, 20% of screen ineligible
      patients had a predicted probability of lung cancer greater than or equal to the
      prevalence of lung cancer (3.7%) among National Lung Screening Trial
      participants; 17% of screen ineligible patients had a predicted probability of
      lung cancer greater than or equal to the American Association for Thoracic
      Surgery threshold (5%) defining high-risk individuals. CONCLUSIONS: Current
      eligibility criteria for lung cancer screening underestimate the risk of lung
      cancer for some individuals who might benefit from lung cancer screening.

PMID- 26298171
TI  - The Effect of Comprehensive Society of Thoracic Surgeons Quality Improvement on
      Outcomes and Failure to Rescue.
AB  - BACKGROUND: The Society of Thoracic Surgeons (STS) quality benchmarks guide
      clinical outcome improvement in cardiac surgery. Failure to rescue (FTR) from
      postoperative morbidity is a proposed metric of program quality. We examined the
      effect of a quality improvement initiative guided by STS quality measures on
      outcomes and FTR. METHODS: Prospectively collected STS data on 3,065 consecutive
      patients who underwent nonemergency cardiac operations at a single institution
      from January 1, 2010, to January 31, 2014, were retrospectively analyzed. On
      January 1, 2012, the quality improvement initiative was implemented. Clinical
      outcomes and FTR rates were compared between operations performed before (group
      A) and after (group B) implementation. RESULTS: STS predicted preoperative
      mortality and composite of mortality plus morbidity were similar in group A and
      group B (2.9% +/- 3.7% vs 3.1% +/- 4.0%, p = 0.21; 17.8% +/- 12.1% vs 18.3% +/-
      12.4%, p = 0.24, respectively). However, the observed mortality and composite
      mortality plus morbidity were lower in group B vs group A (31 of 1,576 [2.0%] vs
      46 of 1,489 [3.1%], p = 0.05; 168 of 1,576 [10.7%] vs 301 of 1,489 [20.2%], p =
      0.0001, respectively). Despite clinical outcome improvement, no differences in
      FTR rates were observed across all seven major morbidity indicators in group A vs
      B (35 of 290 [12.1%] vs 19 of 156 [12.1%], p = 1.00, respectively). The finding
      of similarity in the FTR rate remained consistent during procedural subgroup
      analysis for isolated coronary artery bypass grafting in group A vs B (22 of 174
      [12.6%] vs 9 of 77 [11.7%], p = 1.00, respectively). CONCLUSIONS: Implementation
      of quality improvement initiatives significantly improves outcomes without
      affecting FTR rates. Further study is needed to determine if FTR provides
      additive value to quality assessment over existing STS metrics.

PMID- 26298170
TI  - Epidemiology of Stroke in Pediatric Cardiac Surgical Patients Supported With
      Extracorporeal Membrane Oxygenation.
AB  - BACKGROUND: Stroke is a common complication of extracorporeal membrane
      oxygenation (ECMO), and pediatric cardiac surgical patients may be at higher
      risk. Epidemiology and risk factors for stroke in these patients are not well
      characterized. METHODS: We analyzed pediatric (<18 years) cardiac ECMO cases in
      the Extracorporeal Life Support Organization Registry from 2002 to 2013. Cardiac
      surgical patients were identified, and procedures were stratified according to
      The Society of Thoracic Surgeons morbidity categories. The primary outcome was
      any stroke (hemorrhagic or infarction) identified by neuroimaging. Risk factors
      were identified through multivariable logistic regression. RESULTS: We analyzed
      3,517 cardiac surgical patients; 81% with cyanotic disease, and 57% in high-risk
      categories from The Society of Thoracic Surgeons (categories 4 and 5). Overall,
      12% experienced stroke while receiving ECMO, and those with stroke had greater in
      hospital mortality (72% versus 51%; p < 0.0001). In multivariable analysis,
      neonatal status (adjusted odds ratio, 1.8; 95% confidence interval, 1.3 to 2.4),
      lower weight-for-age z score (adjusted odds ratio, 1.1 for each 1-point decrease;
      95% confidence interval, 1.04 to 1.25), and longer ECMO duration (upper quartile
      [>= 167 hours] adjusted odds ratio, 1.4; 95% confidence interval, 1.1 to 1.8)
      were independently associated with increased stroke risk, whereas cyanotic
      disease, The Society of Thoracic Surgeons category, and bypass time were not.
      CONCLUSIONS: This multicenter analysis demonstrates that pediatric cardiac
      surgical patients on ECMO are at high risk of stroke; younger or underweight
      patients and those with longer ECMO duration are at greatest risk, independent of
      procedural complexity. Future study is necessary to determine how anticoagulation
      or other clinical practices can be modified to reduce stroke incidence.

PMID- 26298173
TI  - Characterization of the interactions within fine particle mixtures in highly
      concentrated suspensions for advanced particle processing.
AB  - This paper aims to summarize recent investigations into the dispersion of fine
      particles, and the characterization of their interactions, in concentrated
      suspensions. This summary will provide a better understanding of the current
      status of this research, and will provide useful feedback for advanced particle
      processing. Such processes include the fabrication of functional nanostructures
      and the sustainable beneficiation of complex ores. For example, there has been
      increasing demand for complex ore utilization due to the noticeable decrease in
      the accessibility of high grade and easily extractable ores. In order to maintain
      the sustainable use of mineral resources, the effective beneficiation of complex
      ores is urgently required. It can be successfully achieved only with selective
      particle/mineral dispersion/liberation and the assistance of mineralogical and
      particle characterization. 

PMID- 26298172
TI  - Estradiol enhances the acquisition of lithium chloride-induced conditioned taste
      aversion in castrated male rats.
AB  - The present study examined the effects of short-term treatment with ovarian
      hormones on the acquisition of conditioned taste aversion (CTA). Adult male rats
      were castrated and randomly divided into LiCl- and saline-treated groups.
      Nineteen days after castration, all of the animals were subjected to 23.5-h daily
      water deprivation for seven successive days (day 1 to day 7). On the conditioning
      day (day 8), the rats received either a 4 ml/kg of 0.15 M LiCl or the same dose
      of saline injection immediately after administration of a 2 % sucrose solution
      during the 30-min water session. Starting from day 6, rats in both groups
      received one of the following treatments: daily subcutaneous injection of (1)
      estradiol alone (30 MUg/kg; estradiol benzoate (E) group), (2) estradiol plus
      progesterone (500 MUg; E + progesterone (P) group), or (3) olive oil. From day 9
      to day 11, all of the rats were given daily two-bottle preference tests during
      the 30-min fluid session. The estradiol and estradiol plus progesterone
      treatments in the LiCl groups resulted in significantly lower preference scores
      for the sucrose solution compared with the olive oil treatment groups, but no
      difference in preference score was seen between these two groups. These results
      indicate that both the estradiol and estradiol plus progesterone treatments in
      the LiCl groups enhanced the acquisition of CTA learning and suggest that
      estradiol affects the acquisition of CTA mediated by an activational effect in
      male rats, whereas progesterone treatment does not influence the effects of
      estradiol on the acquisition of CTA.

PMID- 26298174
TI  - Vaccination strategies in lymphoproliferative disorders: Failures and successes.
AB  - Anti-tumor vaccines in lymphoproliferative disorders hold out the prospect of
      effective tumor therapies with minimal side effects. The addition of
      immunotherapy to old and new chemotherapy regimens has improved both response
      rates and disease-free survival, leading in many cases to an extended overall
      survival. Ideally, an antigen that is used for vaccination would be specifically
      expressed in the tumor; it must have an important, causal part in the
      multifactorial process that leads to cancer, and it must be expressed stably even
      after it is attacked by the immune system. Immunotherapies, which aim to activate
      the immune system to kill cancer cells, include strategies to increase the
      frequency or potency of antitumor T cells, to overcome suppressive factors in the
      tumor microenvironment, and to reduce T-cell suppression systemically. In this
      review, we focus on the results of clinical trials of vaccination in lymphoma,
      and discuss potential strategies to enhance the efficacy of immunotherapy in the
      future. 

PMID- 26298175
TI  - Disruption of pre-B-cell receptor signaling jams the WNT/beta-catenin pathway and
      induces cell death in B-cell acute lymphoblastic leukemia cell lines.
AB  - Targeting components of the B-cell receptor (BCR) pathway have dramatically
      improved clinical outcomes in a variety of B-cell malignancies. Despite the well
      documented pathogenic role of BCR precursor (pre-BCR) pathway in B-cell acute
      lymphoblastic leukemia (B-ALL), there is limited available data of therapies that
      aim to disrupt this pathway. To investigate the role of protein kinase Cbeta
      (PKCbeta), a crucial mediator of BCR and pre-BCR signaling, in B-ALL survival, we
      studied the activity of the PKCbeta selective inhibitor enzastaurin (ENZ) in
      seven B-ALL cell lines. Treatment with ENZ resulted in a dose- and time-dependent
      growth inhibition in all cell lines with a relatively higher efficacy in pro-B
      ALL with translocation t(4;11)(q21;q23). The mechanism of growth inhibition was
      by apoptotic induction and cell cycle arrest. A rapid reduction in
      phosphorylation of AKT and its downstream target glycogen synthase kinase 3beta
      (GSK3beta) were observed at 30min after treatment and remaining for 48h. The
      reduction in GSK3beta phosphorylation was associated with a paradoxical
      accumulation of beta-catenin, which was due to a transient loss of beta-catenin
      phosphorylation at ser33-37. In addition, accumulation of beta-catenin was
      associated with downregulation of c-Myc, upregulatiuon of c-Jun, and a subsequent
      protective effect on the tumor suppressor p73. Data in this paper were presented
      in part at 2012 American Society of Hematology Annual Meeting, abstract 1350.

PMID- 26298176
TI  - Effect of hepatitis B and C clearance on atazanavir exposure.

PMID- 26298177
TI  - Persistent organic pollutants carried on plastic resin pellets from two beaches
      in China.
AB  - Microplastics provide a mechanism for the long-range transport of hydrophobic
      chemical contaminants to remote coastal and marine locations. In this study,
      plastic resin pellets were collected from Zhengmingsi Beach and Dongshan Beach in
      China. The collected pellets were analyzed for PAHs, PCBs, HCHs, DDTs, chlordane,
      heptachlor, endosulfan, aldrin, dieldrin and endrin. The total concentration of
      PCBs ranged from 34.7-213.7 ng g(-1) and from 21.5-323.2 ng g(-1) in plastic
      resin pellets for Zhengmingsi Beach and Dongshan Beach respectively. The highest
      concentrations of PCBs were observed for congeners 44, 110, 138, 155 and 200. The
      total concentration of PAHs ranged from 136.3-1586.9 ng g(-1) and from 397.6
      2384.2 ng g(-1) in the plastic pellets, whereas DDTs concentration ranged from
      1.2-101.5 ng g(-1) and from 1.5-127.0 ng g(-1) for the two beaches. The elevated
      concentrations of pollutants appear to be related to extensive industrial
      development, agricultural activity and the use of coal in the area.

PMID- 26298178
TI  - Multidisciplinary rehabilitation after primary brain tumour treatment.
AB  - BACKGROUND: Brain tumours can cause significant disability, which may be amenable
      to multidisciplinary rehabilitation. However, the evidence base for this is
      unclear. This review is an update of a previously published review in the
      Cochrane Database of Systematic Reviews [2013, Issue 1, Art. No. CD009509] on
      'Multidisciplinary rehabilitation after primary brain tumour treatment'.
      OBJECTIVES: To assess the effectiveness of multidisciplinary rehabilitation in
      people after primary brain tumour treatment, especially the types of approaches
      that are effective (settings, intensity). SEARCH METHODS: For this update, we
      searched the Cochrane Central Register of Controlled Trials (CENTRAL, the
      Cochrane Library up to Issue 12 of 12, 2014), MEDLINE (1950 to January week 2,
      2015), EMBASE (1980 to January week 2, 2015), PEDro (1985 to January week 2
      2015), and LILACS (1982 to January week 2, 2015). We checked the bibliographies
      of papers we identified and contacted the authors and known experts in the field
      to seek published and unpublished trials. SELECTION CRITERIA: Controlled clinical
      trials (randomised and non-randomised clinical trials) that compared
      multidisciplinary rehabilitation in primary brain tumour with either routinely
      available local services or lower levels of intervention, or studies that
      compared multidisciplinary rehabilitation in different settings or at different
      levels of intensity. DATA COLLECTION AND ANALYSIS: Three review authors
      independently assessed study quality, extracted data, and performed a 'best
      evidence ' synthesis based on methodological quality. MAIN RESULTS: We did not
      identify any studies for inclusion in the previous version of this review. For
      this update, the literature search identified one low-quality controlled clinical
      trial involving 106 participants. The findings from this study suggest 'low
      level' evidence to support high-intensity ambulatory (outpatient)
      multidisciplinary rehabilitation in reducing short- and long-term motor
      disability (continence, mobility and locomotion, cognition), when compared with
      standard outpatient care. We found improvement in some domains of disability
      (continence, communication) and psychosocial gains were maintained at six months
      follow-up. We found no evidence for improvement in overall participation (quality
      of life and societal relationship). No adverse events were reported as a result
      of multidisciplinary rehabilitation. We found no evidence for improvement in
      quality of life or cost-effectiveness of rehabilitation. It was also not possible
      to suggest best 'dose' of therapy. AUTHORS' CONCLUSIONS: Since the last version
      of this review, one new study has been identified for inclusion. The best
      evidence to date comes from this CCT, which provides low quality evidence that
      higher intensity ambulatory (outpatient) multidisciplinary rehabilitation reduces
      short- and long-term disability in people with brain tumour compared with
      standard outpatient care. Our conclusions are tentative at best, given gaps in
      current research in this area. Although the strength of evidence has increased
      with the identification of a new controlled clinical trial in this updated
      review, further research is needed into appropriate and robust study designs;
      outcome measurement; caregiver needs; evaluation of optimal settings; type,
      intensity, duration of therapy; and cost-effectiveness of multidisciplinary
      rehabilitation in the brain tumour population.

PMID- 26298179
TI  - Rectal bleeding and endoscopy need in Sierra Leone: results of a nationwide,
      cluster-randomized, community-based survey.

PMID- 26298180
TI  - Subcutaneous tuberculosis formation during FOLFIRI and bevacizumab treatment: a
      case report.

PMID- 26298181
TI  - Celiac disease and Hashimoto's thyroiditis: a shared plot?

PMID- 26298182
TI  - Risk of complications and long-term functional alterations after local excision
      of rectal tumors with transanal endoscopic microsurgery (TEM).
AB  - INTRODUCTION: Transanal endoscopic microsurgery (TEM) is a consolidated technique
      for the excision of rectal tumors. However, many aspects relating to its
      morbidity, risk of functional alterations, and therapeutic outcomes are still
      unclear. The aim of this study was to assess the rate of morbidity and fecal
      incontinence after TEM, and to identify associated risk factors. METHODS: We
      prospectively recorded the clinical data of 157 patients who underwent TEM from
      1996 to 2013. Among these, 89 patients answered a questionnaire for the
      assessment of fecal continence at a median follow-up time of 40 months. RESULTS:
      Intraoperative and postoperative TEM complication rates were 3.8 and 20.4%. The
      mortality rate was 0.6%. A distance from the anal verge of more than 6 cm
      correlated with a higher risk of perforation, while patients with cancer were
      more likely to have postoperative bleeding. Incontinence was reported by 32 (36%)
      patients, of which 7 (8%) experienced transitory symptoms only, while 25 (28%)
      reported persistent symptoms. We found a correlation between patients receiving
      preoperative radiotherapy (RT) and the development of fecal incontinence. The
      recurrence rate was 3% (1/32) in pT1, 80% (4/5) in pT2, and 100% (1/1) in pT3.
      After radiotherapy, 7% (1/9) showed a good response (pT0-1), and 18% (2/7) showed
      no response (pT2-3). CONCLUSIONS: TEM is associated with low morbidity but the
      risk of developing functional alterations is not negligible and should be
      discussed with the patient before the operation. Good oncological outcomes are
      possible for early invasive cancers and for selected advanced cancers following a
      good response to preoperative RT.

PMID- 26298183
TI  - Complications and risk prediction in treatment of elderly patients with rectal
      cancer.
AB  - PURPOSE: The primary aim of this study was to characterise complications,
      identify predictors of postoperative morbidity and mortality and to evaluate
      existing risk prediction models in elderly rectal cancer patients. METHODS: An
      observational single-centre study of 330 consecutive patients >75 years treated
      in 1994-2006. Analyses were performed by age group: 75-79 years, 80-85 years and
      >85 years. RESULTS: Total observed in-hospital morbidity was 48.7 %. In
      multivariate analysis, age (OR 1.04, 95 % CI 1.01-1.08, p = 0.04), ASA grade >= 3
      (p = 0.01), acute presentation (OR 1.67, 95 % CI 1.2-13.2, p = 0.02) and major
      surgery (APR OR 3.72, 95 % CI 1.37-10.15, p = 0.01, LAR OR 2.98, 95 % CI 1.14
      7.79, p = 0.03, Hartmann OR 5.46, 95 % CI 1.60-19.28, p = 0.02) were independent
      risk factors for postoperative morbidity. The 30-day mortality was 6.3, 6.4 and
      14.3 % (p = 0.146) in the three age groups, and the 100-day mortality was 8.7,
      10.1 and 22.2 % (p = 0.03), respectively. ASA group 3 (OR 6.21, 95 % CI 4.39
      27.69, p = 0.017), ASA group 4 (OR 32.6, 95 % CI 5.12-207.75, p < 0.001) and
      acute presentation (OR 6.48, 95 % CI 1.62-25.99, p = 0.008) increased the risk of
      100-day mortality. The Physiological and Operative Severity Score for enUmeration
      of Mortality and Morbidity (POSSUM) observed/estimated (O/E) ratio for morbidity
      was 1.05. For 30-day mortality, the colorectal POSSUM (Cr-POSSUM) O/E ratio was
      0.74, Surgical Risk Scale 0.61 and the Association of Coloproctology of Great
      Britain and Ireland (ACPGBI) mortality model 0.63, and for 100-day mortality,
      ratios were 1.12, 0.91 and 0.95, respectively. CONCLUSION: In this series, age
      increased the risk of in-hospital morbidity and 100-day mortality. Cr-POSSUM, SRS
      and ACPGBI overestimated 30-day mortality but predicted 100-day mortality with a
      high degree of accuracy. POSSUM correctly predicted in-hospital morbidity.

PMID- 26298184
TI  - Impact of being underweight on the long-term outcomes of patients with gastric
      cancer.
AB  - BACKGROUND: The aim of this study was to investigate the impact of being
      underweight on the long-term outcomes of gastric cancer patients. METHODS: This
      study reviewed the medical records of 638 patients with gastric cancer who
      underwent gastrectomy between January 2003 and December 2011. The patients were
      divided into three groups according to the WHO classification: underweight (BMI
      <18.5 kg/m(2)), normal weight (BMI >=18.5 and <25 kg/m(2)), and overweight (BMI
      >=25 kg/m(2)). A multivariate analysis was performed to identify prognostic
      factors. RESULTS: The mean BMI immediately before surgery was 22.5 kg/m(2)
      (standard deviation, 3.3 kg/m(2)). According to the BMI subgroup, 73 patients
      (11.4 %) were underweight, 431 patients (67.6 %) were of normal weight, and 134
      patients (21 %) were overweight. The 5-year overall survival (OS) rate was 66.6 %
      in the underweight patients, 81.3 % in the normal weight patients, and 79.9 % in
      the overweight patients (P = 0.001). The OS rate was significantly lower in the
      underweight patients than in the normal weight and overweight patients among
      those with stage I disease, and it was also lower than in the normal weight
      patients among those with stage II and III disease. In the multivariate analysis,
      being underweight was found to be an independent predictor of OS, but it was not
      an independent predictor among patients with stage II and III disease.
      CONCLUSIONS: Being underweight is a simple and reliable predictor of a worse long
      term outcome among gastric cancer patients. Being underweight is considered to be
      associated with a higher risk of non-cancer death.

PMID- 26298185
TI  - Statistical monitoring of data quality and consistency in the Stomach Cancer
      Adjuvant Multi-institutional Trial Group Trial.
AB  - INTRODUCTION: Data quality may impact the outcome of clinical trials; hence,
      there is a need to implement quality control strategies for the data collected.
      Traditional approaches to quality control have primarily used source data
      verification during on-site monitoring visits, but these approaches are hugely
      expensive as well as ineffective. There is growing interest in central
      statistical monitoring (CSM) as an effective way to ensure data quality and
      consistency in multicenter clinical trials. METHODS: CSM with SMARTTM uses
      advanced statistical tools that help identify centers with atypical data patterns
      which might be the sign of an underlying quality issue. This approach was used to
      assess the quality and consistency of the data collected in the Stomach Cancer
      Adjuvant Multi-institutional Trial Group Trial, involving 1495 patients across
      232 centers in Japan. RESULTS: In the Stomach Cancer Adjuvant Multi-institutional
      Trial Group Trial, very few atypical data patterns were found among the
      participating centers, and none of these patterns were deemed to be related to a
      quality issue that could significantly affect the outcome of the trial.
      DISCUSSION: CSM can be used to provide a check of the quality of the data from
      completed multicenter clinical trials before analysis, publication, and
      submission of the results to regulatory agencies. It can also form the basis of a
      risk-based monitoring strategy in ongoing multicenter trials. CSM aims at
      improving data quality in clinical trials while also reducing monitoring costs.

PMID- 26298186
TI  - Effects of organic acids on cadmium and copper sorption and desorption by two
      calcareous soils.
AB  - Low molecular weight organic acids (LMWOAs) present in soil alter equilibrium pH
      of soil, and consequently, affect heavy metal sorption and desorption on soil
      constitutes. This study was conducted to investigate the effects of different
      concentrations (0.1, 1, 2.5, 5, 10, 30, 40, 50, 70, and 100 mM) of citric, malic,
      and oxalic acids on sorption and desorption of cadmium (Cd) and copper (Cu) in
      two calcareous soils. Increasing the concentrations of three LMWOAs decreased the
      equilibrium pH of soil solutions. The results indicated that increase in organic
      acids concentrations generally reduced Cd and Cu sorption in soils. Increase
      concentrations of LMWOAs generally promoted Cd and Cu desorption from soils. A
      valley-like curve was observed for desorption of Cu after the citric acid
      concentration increment in soil 2. Increasing the concentrations of three LMWOAs
      caused a marked decrease in Kd(sorp) values of Cd and Cu in soils. In general,
      citric acid was the most effective organic acid in reducing sorption and
      increasing desorption of both metals, and oxalic acid had the minimal impact. The
      results indicated that LMWOAs had a greater impact on Cu sorption and desorption
      than Cd, which can be attributed to higher stability constants of organic acids
      complexes with Cu compared to Cd. It can be concluded that by selecting suitable
      type and concentration of LMWOAs, mobility, and hence, bioavailability of heavy
      metals can be changed. So, environmental implications concerning heavy metals
      mobility might be derived from these findings.

PMID- 26298187
TI  - Potential human health risk assessment of heavy metals via the consumption of
      tilapia Oreochromis mossambicus collected from contaminated and uncontaminated
      ponds.
AB  - Fish tilapia Oreochromis mossambicus were collected from a contaminated Seri
      Serdang (SS) pond potentially receiving domestic effluents and an uncontaminated
      pond from Universiti Putra Malaysia (UPM). The fish were dissected into four
      parts namely gills, muscles, intestines, and liver. All the fish parts were
      pooled and analyzed for the concentrations of Cd, Cu, Fe, Ni, Pb, and Zn.
      Generally, the concentrations of all metals were low in the edible muscle in
      comparison to the other parts of the fish. It was found that the levels of all
      the heavy metals in the different parts of fish collected from the SS were
      significantly (P<0.05) higher than those from UPM, indicating greater metal
      bioavailabilities in the SS pond. The sediment data also showed a similar pattern
      with significantly (P<0.05) higher metal concentrations in SS than in UPM,
      indicating higher metal contamination in SS. Potential health risk assessments
      based on provisional tolerable weekly intake (PTWI) and the amount of fish
      required to reach the PTWI values, estimated daily intake (EDI), and target
      hazard quotient (THQ) indicated that health risks associated with heavy metal
      exposure via consumption of the fish's muscles were insignificant to human.
      Therefore, the consumption of the edible muscles of tilapia from both ponds
      should pose no toxicological risk of heavy metals since their levels are also
      below the recommended safety guidelines. While it is advisable to discard the
      livers, gills, and intestines of the two tilapia fish populations before
      consumption, there were no potential human health risks of heavy metals to the
      consumers on the fish muscle part.

PMID- 26298188
TI  - Estimation of reproduction number and probable vector density of the first
      autochthonous dengue outbreak in Japan in the last 70 years.
AB  - OBJECTIVES: The first autochthonous case of dengue fever in Japan since 1945 was
      reported on August 27, 2014. Infection was transmitted by Aedes albopictus
      mosquitoes in Tokyo's Yoyogi Park. A total of 65 cases with no history of
      overseas travel and who may have been infected around the park were reported as
      of September 5, 2014. To quantify infection risk of the local epidemic, the
      reproduction number and vector density per person at the onset of the epidemic
      were estimated. METHODS: The estimated probability distribution and the number of
      female mosquitoes per person (MPP) were determined from the data of the initial
      epidemic. RESULTS: The estimated distribution R(0i) for the initial epidemic was
      fitted to a Gamma distribution using location parameter 4.25, scale parameter
      0.19, and shape parameter 7.76 with median 7.78 and IQR (7.21-8.40). The MPP was
      fitted to a normal distribution with mean 5.71 and standard deviation 0.53.
      CONCLUSIONS: Both estimated reproduction number and vector density per person at
      the onset of the epidemic were higher than previously reported values. These
      results indicate the potential for dengue outbreaks in places with elevated
      vector density per person, even in dengue non-endemic countries. To investigate
      the cause of this outbreak, further studies will be needed, including assessments
      of social, behavioral, and environmental factors that may have contributed to
      this epidemic by altering host and vector conditions in the park.

PMID- 26298189
TI  - FOXA2 mRNA expression is associated with relapse in patients with Triple
      Negative/Basal-like breast carcinoma.
AB  - The FOXA family of transcription factors regulates chromatin structure and gene
      expression especially during embryonic development. In normal breast tissue FOXA1
      acts throughout mammary development; whereas in breast carcinoma its expression
      promotes luminal phenotype and correlates with good prognosis. However, the role
      of FOXA2 has not been previously studied in breast cancer. Our purpose was to
      analyze the expression of FOXA2 in breast cancer cells, to explore its role in
      breast cancer stem cells, and to correlate its mRNA expression with
      clinicopathological features and outcome in a series of patients diagnosed with
      breast carcinoma. We analyzed FOXA2 mRNA expression in a retrospective cohort of
      230 breast cancer patients and in cell lines. We also knocked down FOXA2 mRNA
      expression by siRNA to determine the impact on cell proliferation and
      mammospheres formation using a cancer stem cells culture assay. In vitro studies
      demonstrated higher FOXA2 mRNA expression in Triple-Negative/Basal-like cells.
      Further, when it was knocked down, cells decreased proliferation and its
      capability of forming mammospheres. Similarly, FOXA2 mRNA expression was detected
      in 10% (23/230) of the tumors, especially in Triple-Negative/Basal-like phenotype
      (p < 0.001, Fisher's test). Patients whose tumors expressed FOXA2 had increased
      relapses (59 vs. 79%, p = 0.024, log-rank test) that revealed an independent
      prognostic value (HR = 3.29, C.I.95% = 1.45-7.45, p = 0.004, Cox regression). Our
      results suggest that FOXA2 promotes cell proliferation, maintains cancer stem
      cells, favors the development of Triple-Negative/Basal-like tumors, and is
      associated with increase relapses.

PMID- 26298190
TI  - Does infection tilt the scales? Disease effects on the mass balance of an
      invertebrate nutrient recycler.
AB  - While parasites are increasingly recognized as important components of
      ecosystems, we currently know little about how they alter ecosystem nutrient
      availability via host-mediated nutrient cycling. We examined whether infection
      alters the flow of nutrients through hosts and whether such effects depend upon
      host diet quality. To do so, we compared the mass specific nutrient (i.e.,
      nitrogen and phosphorus) release rates, ingestion rates, and elemental
      composition of uninfected Daphnia to those infected with a bacterial parasite, P.
      ramosa. N and P release rates were increased by infection when Daphnia were fed P
      poor diets, but we found no effect of infection on the nutrient release of
      individuals fed P-rich diets. Calculations based on the first law of
      thermodynamics indicated that infection should increase the nutrient release
      rates of Daphnia by decreasing nutrient accumulation rates in host tissues.
      Although we found reduced nutrient accumulation rates in infected Daphnia fed all
      diets, this reduction did not increase the nutrient release rates of Daphnia fed
      the P-rich diet because infected Daphnia fed this diet ingested nutrients more
      slowly than uninfected hosts. Our results thus indicate that parasites can
      significantly alter the nutrient use of animal consumers, which could affect the
      availability of nutrients in heavily parasitized environments. 

PMID- 26298191
TI  - Protection via parasitism: Datura odors attract parasitoid flies, which inhibit
      Manduca larvae from feeding and growing but may not help plants.
AB  - Insect carnivores frequently use olfactory cues from plants to find prey or
      hosts. For plants, the benefits of attracting parasitoids have been
      controversial, partly because parasitoids often do not kill their host insect
      immediately. Furthermore, most research has focused on the effects of solitary
      parasitoids on growth and feeding of hosts, even though many parasitoids are
      gregarious (multiple siblings inhabit the same host). Here, we examine how a
      gregarious parasitoid, the tachinid fly Drino rhoeo, uses olfactory cues from the
      host plant Datura wrightii to find the sphingid herbivore Manduca sexta, and how
      parasitism affects growth and feeding of host larvae. In behavioral trials using
      a Y-olfactometer, female flies were attracted to olfactory cues emitted by
      attacked plants and by cues emitted from the frass produced by larval Manduca
      sexta. M. sexta caterpillars that were parasitized by D. rhoeo grew to lower
      maximum weights, grew more slowly, and ate less of their host plant. We also
      present an analytical model to predict how tri-trophic interactions change with
      varying herbivory levels, parasitization rates and plant sizes. This model
      predicted that smaller plants gain a relatively greater benefit compared to large
      plants in attracting D. rhoeo. By assessing the behavior, the effects of host
      performance, and the variation in ecological parameters of the system, we can
      better understand the complex interactions between herbivorous insects, the
      plants they live on and the third trophic level members that attack them. 

PMID- 26298192
TI  - Resveratrol ameliorates cardiac oxidative stress in diabetes through
      deacetylation of NFkB-p65 and histone 3.
AB  - Resveratrol, a phytoalexin, has recently gained attention for protective effects
      against metabolic and cardiac diseases. The beneficial effects of resveratrol
      have been linked to sirtuin-1 (SIRT-1) activation. However, little is known about
      the effect of resveratrol in cardiac complications associated with diabetes.
      Here, we have demonstrated that resveratrol ameliorates cardiac hypertrophy,
      electrocardiographic abnormalities and oxidative stress in the fructose-fed
      diabetic rat heart. Mechanistic studies revealed that fructose feeding to Sprague
      Dawley rats over a period of 8 weeks leads to cardiac hypertrophy and increased
      oxidative stress through increased activity of NADPH oxidase (NOX) and reactive
      oxygen species production. We found increased activity of nuclear factor kappa B
      (NFkB) p-65 along with decreased SIRT-1 activity in the diabetic heart.
      Resveratrol activates SIRT-1, which deacetylates NFkB-p65 at lysine 310 and
      histone 3 (H3) at lysine 9 position. SIRT1 activation leads to decreased binding
      of NFkB-p65 to DNA and attenuated cardiac hypertrophy and oxidative stress
      through reduced transcription of NADPH oxidase subunits. In vitro analysis also
      revealed that SIRT-1 activation by resveratrol is associated with decreased NFkB
      p65 activity and NOX transcription. Similarly, knockdown or inhibition of SIRT1
      in H9C2 cells increased acetylation of NFkB-p65 K310 and H3K9. Overall, our data
      demonstrated that SIRT-1 activation by resveratrol leads to deacetylation of both
      NFkB-p65 and H3, thereby attenuating cardiac oxidative stress and complications
      in diabetes. 

PMID- 26298193
TI  - Learning with hidden variables.
AB  - Learning and inferring features that generate sensory input is a task
      continuously performed by cortex. In recent years, novel algorithms and learning
      rules have been proposed that allow neural network models to learn such features
      from natural images, written text, audio signals, etc. These networks usually
      involve deep architectures with many layers of hidden neurons. Here we review
      recent advancements in this area emphasizing, amongst other things, the
      processing of dynamical inputs by networks with hidden nodes and the role of
      single neuron models. These points and the questions they arise can provide
      conceptual advancements in understanding of learning in the cortex and the
      relationship between machine learning approaches to learning with hidden nodes
      and those in cortical circuits. 

PMID- 26298194
TI  - Shorter sleep duration is associated with poorer glycemic control in type 2
      diabetes patients with untreated sleep-disordered breathing.
AB  - PURPOSE: The purpose of this study is to explore the impact of sleep duration on
      glycemic control in type 2 diabetes patients with untreated sleep-disordered
      breathing (SDB). METHODS: Ninety type 2 diabetes patients participated in the
      study. SDB was diagnosed using an overnight in-home monitoring device
      (WatchPAT200). Sleep duration was recorded by wrist actigraphy for 7 days.
      Medical records were reviewed for hemoglobin A1c (HbA1c) values. RESULTS: Seventy
      one patients (78.8 %) were diagnosed with SDB [apnea-hypopnea index (AHI) >= 5].
      In patients with SDB, there was no significant relationship between AHI and
      glycemic control. In addition, oxygen desaturation index, minimum oxygen
      saturation, and time spent below oxygen saturation of 90 % were not significantly
      correlated with glycemic control. Sleep duration, however, was inversely
      correlated with HbA1c (r = -0.264, p 0.026). Multiple regression analysis
      adjusting for age, sex, body mass index, insulin use, diabetes duration, and AHI
      revealed that sleep duration was significantly associated with HbA1c (p = 0.005).
      Each hour reduction in sleep duration was associated with a 4.8 % increase in
      HbA1c of its original value (95 % CI 1.5-8.0). CONCLUSION: In type 2 diabetes
      patients with untreated SDB, shorter sleep duration was independently associated
      with poorer glycemic control. Sleep duration optimization may lead to improved
      glycemic control in this population.

PMID- 26298196
TI  - A pilot study of the impact of a novel compression belt on pelvic blood flow in
      healthy postpartum women.

PMID- 26298197
TI  - A time-dependent model for improved biogalvanic tissue characterisation.
AB  - Measurement of the passive electrical resistance of biological tissues through
      biogalvanic characterisation has been proposed as a simple means of
      distinguishing healthy from diseased tissue. This method has the potential to
      provide valuable real-time information when integrated into surgical tools.
      Characterised tissue resistance values have been shown to be particularly
      sensitive to external load switching direction and rate, bringing into question
      the stability and efficacy of the technique. These errors are due to transient
      variations observed in measurement data that are not accounted for in current
      electrical models. The presented research proposes the addition of a time
      dependent element to the characterisation model to account for losses associated
      with this transient behaviour. Influence of switching rate has been examined,
      with the inclusion of transient elements improving the repeatability of the
      characterised tissue resistance. Application of this model to repeat biogalvanic
      measurements on a single ex vivo human colon tissue sample with healthy and
      cancerous (adenocarcinoma) regions showed a statistically significant difference
      (p < 0.05) between tissue types. In contrast, an insignificant difference (p >
      0.05) between tissue types was found when measurements were subjected to the
      current model, suggesting that the proposed model may allow for improved
      biogalvanic tissue characterisation. 

PMID- 26298195
TI  - International collaborative study for establishment of the 2nd WHO International
      Standard for Haemophilus influenzae type b polysaccharide.
AB  - In this report we present the results of a collaborative study for the
      preparation and calibration of a replacement International Standard (IS) for
      Haemophilus influenzae type b polysaccharide (polyribosyl ribitol phosphate; 5-d
      ribitol-(1 -> 1)-beta-d-ribose-3-phosphate; PRP). Two candidate preparations were
      evaluated. Thirteen laboratories from 9 different countries participated in the
      collaborative study to assess the suitability and determine the PRP content of
      two candidate standards. On the basis of the results from this study, Candidate 2
      (NIBSC code 12/306) has been established as the 2nd WHO IS for PRP by the Expert
      Committee of Biological Standards of the World Health Organisation with a content
      of 4.904 +/- 0.185mg/ampoule, as determined by the ribose assays carried out by
      11 of the participating laboratories. 

PMID- 26298198
TI  - Reexcision for positive margins in breast cancer: A predictive score of residual
      disease.
AB  - BACKGROUND: Guidelines recommend re-excision if resection margins are positive in
      lumpectomy for breast cancer. However, residual disease (RD) is not always found.
      The aim of our study was to develop a score to predict RD in re-excision
      specimens. MATERIALS AND METHODS: We carried out a multicenter, retrospective
      study with two population groups. The 'modeling' group was composed of 148
      patients treated in the Centre Hospitalier Poissy-St-Germain or the Georges
      Pompidou European Hospital and the 'validation' group was composed of 67 patients
      treated in Curie Institute. The score was built with a logistic regression model.
      RESULTS: Factors independently associated with RD were: a cumulative length of
      all positive margins>5 mm, invasion by ductal carcinoma in situ only, a
      pathological tumor size>30 mm and a pathological tumor size<30 mm with a
      discrepancy of >50% between pathological and radiological tumor size. The 7-point
      score allowed the classification of patients into three risk groups for RD: low
      (16% of patients experienced RD), moderate (65%) and high (100%). The areas under
      the ROC curve of the score and the logistic model were 0.72(95%CI:0.68-0.75,p =
      0.60). The proportion of RD in each group of the validation population (25%, 48%,
      and 100% in the low, moderate and high group, respectively) confirmed the
      accuracy of the score in an independent population. CONCLUSIONS: This score
      enables the identification of patients at high risk of RD but it cannot provide
      guidance for the decision to undertake re-excision surgery in the low-risk group.
      Further studies are needed to test the score in extensive datasets and better
      identify low-risk patients.

PMID- 26298199
TI  - Update for ASCO 2015 sarcoma sessions.
AB  - There were over 75 oral or poster presentations in last Spring's American Society
      for Clinical Oncology (ASCO) sarcoma sessions. These presentations included
      investigations studying new medical therapy regimens for soft tissue sarcoma
      (STS) patients with advanced disease, research studies on the relative value of
      aggressive local therapies for certain histologies of STS, and innovative
      investigations evaluating prognostic (and potentially therapeutic) implications
      of next generation sequencing of tumors and circulating tumor DNA. This paper
      serves to review select presentations from the sessions in the meeting. 

PMID- 26298200
TI  - How should we manage small focal pure ground-glass opacity nodules on high
      resolution computed tomography? A single institute experience.
AB  - BACKGROUND: Although the detection of pure ground-glass opacity (p-GGO) nodules
      on high-resolution chest computed tomography (HRCT) often implies a diagnosis of
      lung adenocarcinoma, the management of p-GGO nodules remains under discussion.
      OBJECTIVE: To assess the correlation between the radiological and pathological
      diagnoses of small p-GGO on HRCT. PATIENTS AND METHODS: This is a single
      institution retrospective study. We analyzed 89 consecutive patients, including
      33 patients with resected p-GGO nodule(s) equal or less than 20 mm in maximal
      diameter on axial images of HRCT. RESULTS: Thirty-nine patients underwent
      locoregional treatment (Treatment group), including surgical resection in 33 and
      stereotactic body radiation therapy in six. The remaining 50 patients were
      observed (Observation group) using periodic chest HRCT. The median follow-up time
      was 30.4 (4.9-102.5) months in the Treatment group and 44.8 (0.4-1125.8) months
      in the Observation group. During the follow-up period, the p-GGO nodules
      increased in size in eight patients over a median of 20.6 (12.1-50.6) months,
      with increased attenuation in three patients over a median of 20.6 (12.1-50.6)
      months, and either decreased in size or disappeared in four patients over a
      median of 6.9 (2.0-11.2) months. Thirty-three patients with 47 nodules underwent
      surgical resection, including 41 adenocarcinomas, one neuroendocrine tumor, three
      cases of atypical adenomatous hyperplasia and two benign lesions. The frequency
      of invasive adenocarcinoma was higher among the larger p-GGO nodules.
      CONCLUSIONS: Careful observation and decision making with respect to the timing
      of intervention in cases of p-GGO nodules are warranted.

PMID- 26298201
TI  - Complex I dysfunction underlies the glycolytic switch in pulmonary hypertensive
      smooth muscle cells.
AB  - ATP is essential for cellular function and is usually produced through oxidative
      phosphorylation. However, mitochondrial dysfunction is now being recognized as an
      important contributing factor in the development cardiovascular diseases, such as
      pulmonary hypertension (PH). In PH there is a metabolic change from oxidative
      phosphorylation to mainly glycolysis for energy production. However, the
      mechanisms underlying this glycolytic switch are only poorly understood. In
      particular the role of the respiratory Complexes in the mitochondrial dysfunction
      associated with PH is unresolved and was the focus of our investigations. We
      report that smooth muscle cells isolated from the pulmonary vessels of rats with
      PH (PH-PASMC), induced by a single injection of monocrotaline, have attenuated
      mitochondrial function and enhanced glycolysis. Further, utilizing a novel live
      cell assay, we were able to demonstrate that the mitochondrial dysfunction in PH
      PASMC correlates with deficiencies in the activities of Complexes I-III. Further,
      we observed that there was an increase in mitochondrial reactive oxygen species
      generation and mitochondrial membrane potential in the PASMC isolated from rats
      with PH. We further found that the defect in Complex I activity was due to a loss
      of Complex I assembly, although the assembly of Complexes II and III were both
      maintained. Thus, we conclude that loss of Complex I assembly may be involved in
      the switch of energy metabolism in smooth muscle cells to glycolysis and that
      maintaining Complex I activity may be a potential therapeutic target for the
      treatment of PH. 

PMID- 26298202
TI  - Outcome after BCG treatment for urinary bladder cancer may be influenced by
      polymorphisms in the NOS2 and NOS3 genes.
AB  - PURPOSE: Bacillus Calmette-Guerin (BCG)-treatment is an established treatment for
      bladder cancer, but its mechanisms of action are not fully understood. High-risk
      non-muscle invasive bladder-cancer (NMIBC)-patients failing to respond to BCG
      treatment have worse prognosis than those undergoing immediate radical cystectomy
      and identification of patients at risk for BCG-failure is of high priority.
      Several studies indicate a role for nitric oxide (NO) in the cytotoxic effect
      that BCG exerts on bladder cancer cells. In this study we investigated whether NO
      synthase (NOS)-gene polymorphisms, NOS2-promoter microsatellite (CCTTT)n, and the
      NOS3-polymorphisms-786T>C (rs2070744) and Glu298Asp (rs1799983), can serve as
      possible molecular markers for outcome after BCG-treatment for NMIBC. MATERIALS
      AND METHODS: All NMIBC-patients from a well-characterized population based cohort
      were analyzed (n=88). Polymorphism data were combined with information from 15
      years of clinical follow-up. The effect of BCG-treatment on cancer-specific death
      (CSD), recurrence and progression in patients with varying NOS-genotypes were
      studied using Cox proportional hazard-models and log rank tests. RESULTS: BCG
      treatment resulted in significantly better survival in patients without (Log
      rank: p=0.006; HR: 0.12, p=0.048), but not in patients with a long version
      ((CCTTT)n ?13 repeats) of the NOS2-promoter microsatellite. The NOS3
      rs2070744(TT) and rs1799983(GG)-genotypes showed decreased risk for CSD (Log
      rank(TT): p=0.001; Log rank(GG): p=0.010, HR(GG): 0.16, p=0.030) and progression
      (Log rank(TT): p<0.001, HR(TT): 0.05, p=0.005; Log rank(GG): p<0.001, HR(GG):
      0.10, p=0.003) after BCG-therapy compared to the other genotypes. There was also
      a reduction in recurrence in BCG-treated patients that was mostly genotype
      independent. Analysis of combined genotypes identified a subgroup of 30% of the
      BCG-treated patients that did not benefit from BCG-treatment. CONCLUSIONS: Our
      results suggest that the investigated polymorphisms influence patient response to
      BCG-treatment and thus may serve as possible markers for identification of BCG
      failures.

PMID- 26298203
TI  - NOSH-sulindac (AVT-18A) is a novel nitric oxide- and hydrogen sulfide-releasing
      hybrid that is gastrointestinal safe and has potent anti-inflammatory, analgesic,
      antipyretic, anti-platelet, and anti-cancer properties.
AB  - Sulindac is chemopreventive and has utility in patients with familial adenomatous
      polyposis; however, side effects preclude its long-term use. NOSH-sulindac (AVT
      18A) releases nitric oxide and hydrogen sulfide, was designed to be a safer
      alternative. Here we compare the gastrointestinal safety, anti-inflammatory,
      analgesic, anti-pyretic, anti-platelet, and anti-cancer properties of sulindac
      and NOSH-sulindac administered orally to rats at equimolar doses.
      Gastrointestinal safety: 6h post-administration, number/size of hemorrhagic
      lesions in stomachs were counted. Tissue samples were frozen for PGE2, SOD, and
      MDA determination. Anti-inflammatory: 1h after drug administration, the volume of
      carrageenan-induced rat paw edemas was measured for 5h. Anti-pyretic: fever was
      induced by LPS (ip) an hour before administration of the test drugs, core body
      temperature was measured hourly for 5h. Analgesic: time-dependent analgesic
      effects were evaluated by carrageenan-induced hyperalgesia. Antiplatelet: anti
      aggregatory effects were studied on collagen-induced platelet aggregation of
      human platelet-rich plasma. Anti-cancer: We examined the effects of NOSH-sulindac
      on the growth properties of 12 human cancer cell lines of six different tissue
      origins. Both agents reduced PGE2 levels in stomach tissue; however, NOSH
      sulindac did not cause any stomach ulcers, whereas sulindac caused significant
      bleeding. Lipid peroxidation induced by sulindac was higher than that from NOSH
      sulindac. SOD activity was significantly lowered by sulindac but increased by
      NOSH-sulindac. Both agents showed similar anti-inflammatory, analgesic, anti
      pyretic, and anti-platelet activities. Sulindac increased plasma TNFalpha whereas
      this rise was lower in the NOSH-sulindac-treated animals. NOSH-sulindac inhibited
      the growth of all cancer cell lines studied, with potencies of 1000- to 9000-fold
      greater than that of sulindac. NOSH-sulindac inhibited cell proliferation,
      induced apoptosis, and caused G2/M cell cycle block. These results demonstrate
      that NOSH-sulindac is gastrointestinal safe, and maintains the anti-inflammatory,
      analgesic, antipyretic, and antiplatelet properties of its parent compound
      sulinsac, with anti-growth activity against a wide variety of human cancer cells.

PMID- 26298205
TI  - Psychological distress and mortality in patients with acute dyspnea: data from
      the Akershus Cardiac Examination (ACE) 2 Study.
AB  - OBJECTIVE: To test the hypotheses that anxiety and depression are associated with
      etiology, disease severity and mortality in patients hospitalized with acute
      dyspnea. METHODS: The Hospital Anxiety and Depression Scale was completed within
      48h of admission in 185 patients. A subscale score of >=8 was regarded as
      clinically significant. The etiology and severity of dyspnea on admission and all
      cause mortality during follow-up (median, 2.3years) were recorded. RESULTS:
      Anxiety and depression were more prevalent in patients with chronic obstructive
      pulmonary disease (COPD) (n=53; 42% and 31%) and heart failure (HF) (n=80; 33%
      and 23%) than in other causes of acute dyspnea (15% and 11%). Psychological
      distress was not associated with clinical status or cardiac biomarkers. Anxiety,
      but not depression, was associated with increased mortality, also when adjusting
      for cardiac biomarkers in multivariate Cox analysis. In contrast, anxiety was not
      associated with mortality after adjustment for body mass index, history of COPD
      and disease severity (hazard ratio, 1.67; 95% confidence interval, 0.92-3.00).
      CONCLUSION: Psychological distress was associated with COPD and HF as etiology of
      acute dyspnea, but not with disease severity. Anxious patients had a higher
      mortality rate, but this association was related to the presence and severity of
      COPD.

PMID- 26298206
TI  - Emergence of whooping cough: notes from three early epidemics in Persia.
AB  - Whooping cough is a relatively new infectious disease afflicting human beings,
      compared with other infectious diseases, and is undergoing a resurgence despite
      decades of vaccination. The oldest known epidemic is thought to be the Paris
      outbreak of 1578. In this Historical Review, we describe three epidemics of
      whooping cough in Persia, which although arising roughly one century before the
      Paris outbreak, have not been examined in detail. A great amount of
      epidemiological detail was reported that not only distinguishes the various
      stages and complications of whooping cough, but also reveals unique immunological
      aspects of this disease. The first of these epidemics is the oldest recorded
      whooping cough epidemic. On the basis of epidemiological features, we propose
      that this whooping cough epidemic was the first to have taken place in Persia and
      might have been part of the first pandemic. This theory pushes back the date of
      first documented emergence of whooping cough by almost a century, which matches
      molecular data about its spread. Here, we discuss features of these early
      epidemics in relation to their initial emergence, potential origins, and spread
      to Europe. 

PMID- 26298204
TI  - The role of lipoxygenases in pathophysiology; new insights and future
      perspectives.
AB  - Lipoxygenases (LOXs) are dioxygenases that catalyze the formation of
      corresponding hydroperoxides from polyunsaturated fatty acids such as linoleic
      acid and arachidonic acid. LOX enzymes are expressed in immune, epithelial, and
      tumor cells that display a variety of physiological functions, including
      inflammation, skin disorder, and tumorigenesis. In the humans and mice, six LOX
      isoforms have been known. 15-LOX, a prototypical enzyme originally found in
      reticulocytes shares the similarity of amino acid sequence as well as the
      biochemical property to plant LOX enzymes. 15-LOX-2, which is expressed in
      epithelial cells and leukocytes, has different substrate specificity in the
      humans and mice, therefore, the role of them in mammals has not been established.
      12-LOX is an isoform expressed in epithelial cells and myeloid cells including
      platelets. Many mutations in this isoform are found in epithelial cancers,
      suggesting a potential link between 12-LOX and tumorigenesis. 12R-LOX can be
      found in the epithelial cells of the skin. Defects in this gene result in
      ichthyosis, a cutaneous disorder characterized by pathophysiologically dried skin
      due to abnormal loss of water from its epithelial cell layer. Similarly, eLOX-3,
      which is also expressed in the skin epithelial cells acting downstream 12R-LOX,
      is another causative factor for ichthyosis. 5-LOX is a distinct isoform playing
      an important role in asthma and inflammation. This isoform causes the
      constriction of bronchioles in response to cysteinyl leukotrienes such as LTC4,
      thus leading to asthma. It also induces neutrophilic inflammation by its
      recruitment in response to LTB4. Importantly, 5-LOX activity is strictly
      regulated by 5-LOX activating protein (FLAP) though the distribution of 5-LOX in
      the nucleus. Currently, pharmacological drugs targeting FLAP are actively
      developing. This review summarized these functions of LOX enzymes under
      pathophysiological conditions in mammals. 

PMID- 26298209
TI  - Shaeer's Corporal Rotation III: Shortening-Free Correction of Congenital Penile
      Curvature-The Noncorporotomy Technique.
AB  - BACKGROUND: Shortening-free correction of congenital ventral penile curvature by
      rotation of the corpora cavernosa was first introduced in 2006 (Shaeer's corporal
      rotation I). The basic principle was shifting the concavity of both corpora
      cavernosa from the ventral aspect of the penis to the lateral aspects, in
      opposition. Rotation was achieved by approximating short parallel incisions on
      the dorsum of both corpora cavernosa. In 2008, we reported modification of the
      technique (Shaeer's corporal rotation II), in which the incisions spanned the
      whole length of the corpora cavernosa. OBJECTIVE: The current modification,
      Shaeer's corporal rotation III (the noncorporotomy technique) simplifies corporal
      rotation further and addresses shortcomings. DESIGN, SETTING, AND PARTICIPANTS:
      This is a retrospective study of 127 cases of congenital ventral penile curvature
      25-90 degrees  operated at Kamal Shaeer Hospital, Cairo, Egypt, from 2009 to
      2015. SURGICAL PROCEDURE: The neurovascular bundle was mobilized, and the corpora
      were rotated by approximating premarked respective points on either side of the
      deep dorsal vein using polyester sutures without incising the tunica albuginea.
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Intraoperative postrotation angle
      and erect length and girth. RESULTS AND LIMITATIONS: On-table measurements showed
      a mean prerotation erection angle of 66.5 degrees  +/- 17.9 degrees  (range: 25
      90 degrees ; median 65 degrees ). Following rotation, the angle was 0.47 degrees 
      +/- 1.8 degrees  (p<0.001) and length was 0.06 +/- 0.25 cm longer (p=0.007),
      whereas girth was 0.77 +/- 0.9 cm narrower (p<0.001). Complications included 11
      cases (8.7%) of ventral wound gaping and 3 (2.4%) with mild recurrence not
      requiring correction. The International Index of Erectile Function was 24.99 +/-
      0.9, with an increase of 13.35 +/- 3.4 over the preoperative state (p<0.001).
      CONCLUSIONS: Shaeer's corporal rotation III enables correction of any degree of
      ventral congenital penile curvature, with neither shortening nor erectile
      dysfunction. PATIENT SUMMARY: Shaeer's corporal rotation is a surgical technique
      for correction of severe degrees of innate downward curvature of the penis,
      without shortening.

PMID- 26298208
TI  - An Arterial Based Complexity (ABC) Scoring System to Assess the Morbidity Profile
      of Partial Nephrectomy.
AB  - BACKGROUND: Tumor characteristics affect surgical complexity and outcomes of
      partial nephrectomy (PN). OBJECTIVE: To develop an Arterial Based Complexity
      (ABC) scoring system to predict morbidity of PN. DESIGN, SETTING, AND
      PARTICIPANTS: Four readers independently scored contrast-enhanced computed
      tomography images of 179 patients who underwent PN. INTERVENTION: Renal cortical
      masses were categorized by the order of vessels needed to be transected/dissected
      during PN. Scores of 1, 2, 3S, or 3H were assigned to tumors requiring
      transection of interlobular and arcuate arteries, interlobar arteries, segmental
      arteries, or in close proximity of the renal hilum, respectively during PN.
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Interobserver variability was
      assessed with kappa values and percentage of exact matches between each pairwise
      combination of readers. Linear regression was used to evaluate the association
      between reference scores and ischemia time, estimated blood loss, and estimated
      glomerular filtration rates at 6 wk and 6 mo after surgery adjusted for baseline
      estimated glomerular filtration rate. Fisher's exact test was used to test for
      differences in risk of urinary fistula formation by reference category
      assignment. RESULTS AND LIMITATIONS: Pairwise comparisons of readers' score
      assignments were significantly correlated (all p<0.0001); average kappa = 0.545
      across all reader pairs. The average proportion of exact matches was 69%. Linear
      regression between the complexity score system and surgical outcomes showed
      significant associations between reference category assignments and ischemia time
      (p<0.0001) and estimated blood loss (p=0.049). Fisher's exact test showed a
      significant difference in risk of urinary fistula formation with higher reference
      category assignments (p=0.028). Limitations include use of a single institutional
      cohort to evaluate our system. CONCLUSIONS: The ABC scoring system for PN is
      intuitive, easy to use, and demonstrated good correlation with perioperative
      morbidity. PATIENT SUMMARY: The ABC scoring system is a novel anatomy
      reproducible tool developed to help patients and doctors understand the
      complexity of renal masses and predict the outcomes of kidney surgery.

PMID- 26298210
TI  - Bridging the Gap in Upper Tract Urothelial Carcinoma.

PMID- 26298207
TI  - Hypoxia, Hypoxia-inducible Transcription Factors, and Renal Cancer.
AB  - CONTEXT: Renal cancer is a common urologic malignancy, and therapeutic options
      for metastatic disease are limited. Most clear cell renal cell carcinomas (ccRCC)
      are associated with loss of von Hippel-Lindau tumor suppressor (pVHL) function
      and deregulation of hypoxia pathways. OBJECTIVE: This review summarizes recent
      evidence from genetic and biological studies showing that hypoxia and hypoxia
      related pathways play critical roles in the development and progress of renal
      cancer. EVIDENCE ACQUISITION: We used a systematic search for articles using the
      keywords hypoxia, HIF, renal cancer, and VHL. EVIDENCE SYNTHESIS: Identification
      of the tumor suppressor pVHL has allowed the characterization of important ccRCC
      associated pathways. pVHL targets alpha-subunits of hypoxia-inducible
      transcription factors (HIF) for proteasomal degradation. The two main HIF-alpha
      isoforms have opposing effects on RCC biology, possibly through distinct
      interactions with additional oncogenes. Furthermore, HIF-1alpha activity is
      commonly diminished by chromosomal deletion in ccRCCs, and increased HIF-1
      activity reduces tumor burden in xenograft tumor models. Conversely,
      polymorphisms at the HIF-2alpha gene locus predispose to the development of
      ccRCCs, and HIF-2alpha promotes tumor growth. Genetic studies have revealed a
      prominent role for chromatin-modifying enzyme genes in ccRCC, and these may
      further modulate specific aspects of the HIF response. This suggests that, rather
      than global activation of HIF, specific components of the response are important
      in promoting kidney cancer. Some of these processes are already targets for
      current therapeutic strategies, and further dissection of this pathway might
      yield novel methods of treating RCC. CONCLUSIONS: In contrast to many tumor
      types, HIF-1alpha and HIF-2alpha have opposing effects in ccRCC biology, with HIF
      1alpha acting as a tumor suppressor and HIF-2alpha acting as an oncogene. The
      overall effect of VHL inactivation will depend on fine-tuning of the HIF
      response. PATIENT SUMMARY: High levels of hypoxia-inducible transcription factors
      (HIF) are particularly important in the clear cell type of kidney cancer, in
      which they are no longer properly regulated by the von Hippel-Lindau protein. The
      two HIF-alpha proteins have opposing effects on tumor evolution.

PMID- 26298211
TI  - Further Innovation in Carotid Revascularization Requires Greater Insight into
      Minor Stroke Prevention and Quality of Life Outcomes.

PMID- 26298212
TI  - Dilemma strength as a framework for advancing evolutionary game theory: Reply to
      comments on "Universal scaling for the dilemma strength in evolutionary games".

PMID- 26298213
TI  - The death of recency: Relationship between end-state comfort and serial position
      effects in serial recall: Logan and Fischman (2011) revisited.
AB  - Two experiments examined the dynamic interaction between cognitive resources in
      short-term memory and bimanual object manipulation by extending recent research
      by Logan and Fischman (2011). In Experiment 1, 16 participants completed a
      bimanual end-state comfort task and a memory task requiring serial recall of 12
      words or pictures. The end-state comfort task involved moving two glasses between
      two shelves. Participants viewed the items, performed the end-state comfort task,
      and then serially recalled the items. Recall was evaluated by the presence or
      absence of primacy and recency effects. The end-state comfort effect (ESCE) was
      assessed by the percentage of initial hand positions that allowed the hands to
      end comfortably. The main findings indicated that the ESCE was disrupted; the
      primacy effect remained intact; and the recency effect disappeared regardless of
      the type of memory item recalled. In Experiment 2, 16 participants viewed six
      items, performed an end-state comfort task, viewed another six items, and then
      serially recalled all 12 items. Results were essentially the same as in
      Experiment 1. Findings suggest that executing a bimanual end-state comfort task,
      regardless of when it is completed during a memory task, diminishes the recency
      effect irrespective of the type of memory item. 

PMID- 26298214
TI  - Task-specificity of balance training.
AB  - Despite much research on balance training, it is still unclear whether balance
      training leads to highly task-specific adaptations or rather non-specific
      adaptations. Hence, in this study we examined whether balance training increased
      performance only in the balance task that was trained or also in non-trained
      tasks. Forty healthy participants (28 m 12 f, 25 +/- 4 years, 177 +/- 10 cm, 73
      +/- 14 kg) were assigned to one of two training groups (TGs) or a control group.
      Both TGs completed six sessions over 2 weeks, only the training device differed.
      Before and after the training, performance in the trained task as well as in
      additional untrained tasks was recorded. ANOVAs showed that each TG outperformed
      the other groups only in the task they had trained (e.g., task trained by TG1:
      +225% in TG1, only +41% and +30% in TG2 and control, group*time interaction,
      p<0.001; Untrained task 1: TG1 +48%, TG2 +48%, and control +30%, no significant
      interaction, p=0.72). In summary, 2 weeks of balance training resulted in highly
      task-specific effects, no transfer even to very similar tasks was observed.
      Therefore, we recommend identifying and training exactly those tasks that need
      improvement, and test the efficacy of training programs using specific tests
      instead of general tests with limited functional relevance.

PMID- 26298215
TI  - Does handwriting on a tablet screen affect students' graphomotor execution? A
      comparison between Grades Two and Nine.
AB  - We sought to ascertain how handwriting with a plastic-tipped pen on the screen of
      a digital tablet affects graphomotor execution in students, compared with
      handwriting on paper with a ballpoint pen. We predicted that the modification to
      propriokinesthetic feedback induced by the screen/plastic tip combination would
      differently disturb younger and older students, who rely on perceptual feedback
      either to form letters (former) or to adjust movement execution (latter). Twenty
      eight students from Grades Two and Nine were asked to handwrite the alphabet and
      their names and surnames under the two conditions. Kinematics were recorded using
      the tablet, controlled by Eye and Pen software. Results showed that handwriting
      on the tablet surface with a plastic-tipped pen primarily affected pen pauses in
      the second graders and pen movements in the ninth graders, suggesting a
      disturbance in segment trajectory calculation in the younger participants and
      reduced control of muscular adjustment in the older children. 

PMID- 26298216
TI  - When details of no consequence are the ones that matter.
AB  - After a clinical encounter, a physician considers the value of details from the
      patient's narrative that cannot be clearly interpreted. 

PMID- 26298217
TI  - Clients' psychosocial communication and midwives' verbal and nonverbal
      communication during prenatal counseling for anomaly screening.
AB  - OBJECTIVES: This study focuses on facilitation of clients' psychosocial
      communication during prenatal counseling for fetal anomaly screening. We assessed
      how psychosocial communication by clients is related to midwives' psychosocial
      and affective communication, client-directed gaze and counseling duration.
      METHODS: During 184 videotaped prenatal counseling consultations with 20 Dutch
      midwives, verbal psychosocial and affective behavior was measured by the Roter
      Interaction Analysis System (RIAS). We rated the duration of client-directed
      gaze. We performed multilevel analyses to assess the relation between clients'
      psychosocial communication and midwives' psychosocial and affective
      communication, client-directed gaze and counseling duration. RESULTS: Clients'
      psychosocial communication was higher if midwives' asked more psychosocial
      questions and showed more affective behavior (beta=0.90; CI: 0.45-1.35; p<0.00
      and beta=1.32; CI: 0.18-2.47; p=0.025, respectively). Clients "psychosocial
      communication was not related to midwives" client-directed gaze. Additionally,
      psychosocial communication by clients was directly, positively related to the
      counseling duration (beta=0.59; CI: 0.20-099; p=0.004). CONCLUSIONS: In contrast
      with our expectations, midwives' client-directed gaze was not related with
      psychosocial communication of clients. PRACTICE IMPLICATIONS: In addition to
      asking psychosocial questions, our study shows that midwives' affective behavior
      and counseling duration is likely to encourage client's psychosocial
      communication, known to be especially important for facilitating decision-making.

PMID- 26298218
TI  - Sharing decisions during diagnostic consultations; an observational study in
      pediatric oncology.
AB  - OBJECTIVE: Children and parents need to make important decisions in the period of
      being informed about the diagnosis of childhood cancer. Although parents' and
      children's involvement is legally required, it is unclear whether oncologists
      involve them. This study explored which decisions families face, how oncologists
      involve them in shared decision-making (SDM) and which factors are associated
      with this process. METHODS: Forty-three families with children, starting
      treatment for childhood cancer, were recruited from three Dutch academic
      pediatric oncology clinics. Diagnostic consultations were audio-taped and coded
      with the OPTION. RESULTS: On average, 3.5 decisions were discussed per
      consultation. Most frequently discussed decisions concerned registration in a
      patient database (42%) and how to deal with hair loss (33%). Oncologists'
      assistance in SDM focused on giving information and ensuring the parents' and the
      child's understanding. The hospital in which children were treated (F(2,2)=5.39,
      p=.01) and discussing trial participation (F(1,1)=8.11, p=.01) were associated
      with oncologists' assistance. CONCLUSION: Decision-making during diagnostic
      consultations appears to focus on non-treatment related decisions. Oncologists'
      assistance mostly concerned sharing information, instead of SDM. PRACTICE
      IMPLICATIONS: Additional research is needed to provide insight in how to increase
      oncologists' assistance, while taking into account children's and parents'
      preferences concerning SDM.

PMID- 26298220
TI  - Communication training: Skills and beyond.
AB  - OBJECTIVES: As communication is a central part of every interpersonal meeting
      within healthcare and research reveals several benefits of effective
      communication, we need to teach students and practitioners how to communicate
      with patients and with colleagues. This paper reflects on what and how to teach.
      METHODS: In the previous century two major changes occurred: clinical
      relationship between doctor and patient became important and patients became
      partners in care. Clinicians experienced that outcome and especially compliance
      was influenced by the relational aspect and in particular by the communicative
      skills of the physician. This paper reflects on teaching and defines problems. It
      gives some implications for the future. RESULTS: Although communication skills
      training is reinforced in most curricula all over the word, huge implementation
      problems arise; most of the time a coherent framework is lacking, training is
      limited in time, not integrated in the curriculum and scarcely contextualized,
      often no formal training nor teaching strategies are defined. Moreover evidence
      on communication skills training is scarce or contradictory. CONCLUSIONS: Knowing
      when, what, how can be seen as an essential part of skills training. But students
      need to be taught to reflect on every behavior during every medical consultation.
      PRACTICE IMPLICATIONS: Three major implications can be helpful to overcome the
      problems in communication training. First research and education on healthcare
      issues need to go hand in hand. Second, students as well as healthcare
      professionals need a toolkit of basic skills to give them the opportunity not
      only to tackle basic and serious problems, but to incorporate these skills and to
      be able to use them in a personal and creative way. Third, personal reflection on
      own communicative actions and dealing with interdisciplinary topics is a core
      business of medical communication and training.

PMID- 26298219
TI  - Technology-delivered adaptations of motivational interviewing for health-related
      behaviors: A systematic review of the current research.
AB  - OBJECTIVES: The aims of this paper were to describe and evaluate the methods and
      efficacy of technology-delivered motivational interviewing interventions (TAMIs),
      discuss the challenges and opportunities of TAMIs, and provide a framework for
      future research. METHODS: We reviewed studies that reported using motivational
      interviewing (MI) based components delivered via technology and conducted ratings
      on technology description, comprehensiveness of MI, and study methods. RESULTS:
      The majority of studies were fully-automated and included at least one form of
      media rich technology to deliver the TAMI. Few studies provided complete
      descriptions of how MI components were delivered via technology. Of the studies
      that isolated the TAMI effects, positive changes were reported. CONCLUSION:
      Researchers have used a range of technologies to deliver TAMIs suggesting
      feasibility of these methods. However, there are limited data regarding their
      efficacy, and strategies to deliver relational components remain a challenge.
      Future research should better characterize the components of TAMIs, empirically
      test the efficacy of TAMIs with randomized controlled trials, and incorporate
      fidelity measures. PRACTICE IMPLICATIONS: TAMIs are feasible to implement and
      well accepted. These approaches offer considerable potential to reduce costs,
      minimize therapist and training burden, and expand the range of clients that may
      benefit from adaptations of MI.

PMID- 26298221
TI  - Reporting and Methodological Quality of Randomised Controlled Trials in Vascular
      and Endovascular Surgery.
AB  - BACKGROUND: Randomised controlled trials (RCTs) are subject to bias if they lack
      methodological quality. Moreover, optimal and transparent reporting of RCT
      findings aids their critical appraisal and interpretation. OBJECTIVES: The aim of
      this study was to ascertain whether the methodological and reporting quality of
      RCTs in vascular and endovascular surgery is improving. METHODS: The most recent
      75 and oldest 75 RCTs published in leading journals over a 10-year period (2003
      2012) were identified. The reporting quality and methodological quality data of
      the old and new RCTs were extracted and compared. The former was analysed using
      the Consolidated Standards of Reporting Trials (CONSORT) statement, the latter
      with the Scottish Intercollegiate Guidelines Network (SIGN) checklist. RESULTS:
      Reporting quality measured by CONSORT was better in the new studies than in the
      old studies (0.68 [95% CI, 0.66-0.7] vs. 0.60 [95% CI, 0.58-0.62], p < .001);
      however, both new and old studies had similar methodological quality measured by
      SIGN (0.9 [IQR 0.1] vs. .09 [IQR: 0.2], p = .787). Unlike clinical items, the
      methodological items of the CONSORT statement were not well reported in old and
      new RCTs. More trials in the new group were endovascular related (33.33% vs.
      17.33%, p = .038) and industry sponsored (28% vs. 6.67%, p = .001). CONCLUSIONS:
      Despite some progress, there remains room for improvement in the reporting
      quality of RCTs in vascular and endovascular surgery. The methodological quality
      of recent RCTs is similar to that of trials performed >10 years ago.

PMID- 26298222
TI  - Non-invasive Carotid Artery Imaging to Identify the Vulnerable Plaque: Current
      Status and Future Goals.
AB  - BACKGROUND: The current clinical practise to determine if a patient should
      undergo carotid intervention to prevent stroke is to determine the clinical
      features combined with degree of carotid stenosis. However, this does not
      accurately determine the individual patient's risk for future stroke. A thin
      fibrous cap, a large lipid core, high macrophage count, and intraplaque
      haemorrhage have all been identified as markers of the so-called "vulnerable"
      plaque being related to a higher stroke risk. There is a need to assess the
      accuracy of in vivo imaging to identify vulnerable plaque characteristics,
      thereby enabling in vivo risk stratification to guide clinical decision-making.
      METHODS: The aim of this topical review is to assess the roles of currently
      available imaging modalities that are applied in clinical practice and those
      experimental techniques that are close to clinical translation in defining
      carotid plaque characteristics and in informing clinical practice. RESULTS:
      Ultrasound is a low cost and ready available low-risk tool, but it lacks the
      accuracy to reliably detect individual plaque components and characteristics.
      Computed tomography is considered to be the best imaging technique to identify
      calcification in the carotid plaque. Magnetic resonance imaging (MRI) can
      identify most described plaque characteristics with moderate to good agreement.
      Positron emission tomography allows assessment of specific metabolic functions
      with tracers labelled with positron emitting radio-isotopes, but limited spatial
      resolution makes anatomic precision imprecise. CONCLUSION: MRI has demonstrated
      the most potential, with good sensitivity and specificity for most plaque
      characteristics. However, currently there is no single imaging modality that can
      reliably identify the vulnerable plaque in relation to development of future
      stroke.

PMID- 26298223
TI  - Emergency Percutaneous Closure of an Iatrogenic Atrial Septal Defect Causing
      Right-to-Left Shunt and Severe Refractory Hypoxemia After Pulmonary Vein
      Isolation.

PMID- 26298224
TI  - Venous Strangulation as an Unusual Cause of MitraClip System Delivery Failure.

PMID- 26298225
TI  - Transapical Mitral Valve Implantation for the Treatment of Severe Native Mitral
      Valve Stenosis in a Prohibitive Surgical Risk Patient: Importance of
      Comprehensive Cardiac Computed Tomography Procedural Planning.

PMID- 26298226
TI  - Acute Kidney Injury in Patients With Chronic Kidney Disease Undergoing Internal
      Carotid Artery Stent Implantation.
AB  - OBJECTIVES: This study sought to investigate acute kidney injury (AKI) following
      carotid artery stenting (CAS). BACKGROUND: Few data exist on AKI following CAS.
      METHODS: This study evaluated 126 chronic kidney disease (CKD) patients who
      underwent CAS. The risk for contrast-induced AKI was defined by the Mehran score.
      Hemodynamic depression (i.e., periprocedural systolic blood pressure <90 mm Hg or
      heart rate <60 beats/min), AKI (i.e., an increase of >=0.3 mg/dl in the serum
      creatinine concentration at 48 h), and 30-day major adverse events (including
      death, stroke, and acute myocardial infarction) were assessed. RESULTS: AKI
      occurred in 26 patients (21%). Although baseline kidney function and contrast
      volume were similar in the AKI group and the non-AKI group, the risk score was
      higher (10 +/- 3 vs. 8 +/- 3; p = 0.032), and hemodynamic depression (mostly due
      to hypotension) (65.5% vs. 35%; p = 0.005) was more common in the AKI group. The
      threshold of hemodynamic depression duration for AKI development was 2.5 min
      (sensitivity 54%, specificity 82%). Independent predictors of AKI were
      hemodynamic depression (odds ratio [OR]: 4.01; 95% confidence interval [CI]: 1.07
      to 15.03; p = 0.009), risk score (OR: 1.29; 95% CI: 1.03 to 1.60; p = 0.024), and
      male sex (OR: 6.07; 95% CI: 1.18 to 31.08; p = 0.021). Independent predictors of
      30-day major adverse events that occurred more often in the AKI group (19.5% vs.
      7%; p = 0.058) were AKI (HR: 4.83; 95% CI: 1.10 to 21.24; p = 0.037) and
      hemodynamic depression (HR: 5.58; 95% CI: 1.10 to 28.31; p = 0.038). CONCLUSIONS:
      AKI in CKD patients undergoing CAS is mostly due to hemodynamic depression and is
      associated with a higher 30-day major adverse events rate.

PMID- 26298227
TI  - Hybrid Strategy for Long Diffuse Coronary Lesion.

PMID- 26298228
TI  - Chest Pain Post-Aortic Valve Surgery: Is It Serious?

PMID- 26298229
TI  - How direct is social perception?

PMID- 26298230
TI  - Potential role of reduced environmental UV exposure as a driver of the current
      epidemic of atopic dermatitis.
AB  - The basis for the sudden and dramatic increase in atopic dermatitis (AD) and
      related atopic diseases in the second half of the 20th century is unclear. The
      hygiene hypothesis proposes that the transition from rural to urban living leads
      to reduced childhood exposure to pathogenic microorganisms. Hence instead of
      having the normal TH1 bias and immune tolerance because of repeated exposure to
      pathogens, urban dwellers have TH2 cell immune activity and atopic disease in a
      more sterile environment. Various other environmental exposures have been
      implicated in the explosion of AD (and atopic disorders in general), including
      breast-feeding, tobacco smoking, alcohol consumption, and exposure to
      domesticated furry pets. Notably, the key role of a compromised barrier of
      neonatal skin as a predisposing factor in the development of childhood AD has
      recently been demonstrated. In this article we review the salubrious effects of
      suberythemogenic doses of UVB irradiation for the skin barrier. We then discuss
      how the lack of sufficient UVB exposure could have contributed to the rapid
      increase in the incidence of AD in developed countries. This hypothesis offers a
      separate but not competing partial explanation, which should be viewed as not
      discounting the role of the etiopathogenic factors that also could influence the
      prevalence of atopic disorders. 

PMID- 26298231
TI  - Intracrine steroid production and mammalian target of rapamycin pathways in
      pulmonary lymphangioleiomyomatosis.
AB  - Lymphangioleiomyomatosis (LAM) is a rare, potentially fatal disease primarily
      affecting young women. Estrogens enhance cell proliferation and progression of
      the tumor. Clinical trials using molecularly targeted agents such as endocrine
      manipulation and mammalian target of rapamycin (mTOR) inhibitors are in progress,
      but the status of these molecules, including aromatase and mTOR, has not been
      explored in LAM tissue. We first examined immunoreactivity for sex steroid
      receptors (estrogen receptor [ER] alpha, ERbeta, progesterone receptor, androgen
      receptor), sex steroid-synthesizing enzymes (aromatase, steroid sulfatase, 17beta
      hydroxysteroid dehydrogenase 1, 5alpha-reductases), apoptotic suppression factor
      (Bcl-2), and factors involved in the mTOR signaling pathway in 30 pulmonary LAM
      tissues. Immunoreactivity for ERalpha, ERbeta, progesterone receptor, aromatase,
      and Bcl-2 was significantly more abundant in epithelioid cells, whereas the
      status of androgen receptor, 5alpha-reductases, and phospho-mTOR signaling was
      not different in epithelioid and spindle-shaped LAM cells. We further examined
      the correlation among H scores of these markers using hierarchical clustering
      analysis. The results indicated that LAM tumors can be further classified into
      "aromatase" and "mTOR" groups on the basis of the patterns of immunoreactivity,
      and the 2 types could benefit from different modes of therapy. 

PMID- 26298232
TI  - A rare case of spontaneous cricothyroid joint dislocation.
AB  - Post-traumatic cricothyroid joint dislocation is reported in the literature.
      Trauma of the laryngeal framework is the most common cause. As a result,
      spontaneous non-traumatic cricothyroid joint dislocation is very rarely
      described. We report the case of a patient with spontaneous cricothyroid joint
      dislocation with the aim of reporting the diagnostic and therapeutic findings
      related to this rare entity. History and physical examination may suggest
      diagnosis. Computed tomography scan can confirm diagnosis and detect coexistence
      of anatomic anomalies of the neck. Reduction of dislocation may be easily
      performed in outpatient setting, producing immediate relief from dysphonia and
      neck pain. As CTJ dislocation is a speech-related disorder, appropriate speech
      therapy is advisable in order to avoid relapse. 

PMID- 26298233
TI  - Transoral surgery for laryngo-pharyngeal cancer - The paradigm shift of the head
      and cancer treatment.
AB  - Transoral surgery is a less invasive treatment that is becoming a major strategy
      in the treatment of laryngo-pharyngeal cancer. It is a minimally invasive
      approach that has no skin incision and limits the extent of tissue dissection,
      disruption of speech and swallowing muscles, blood loss, damage to major
      neurovascular structures, and injury to normal tissue. Transoral approaches to
      the laryngo-pharynx, except for early glottis cancer, had been limited
      traditionally to tumors that can be observed directly and manipulated with
      standard instrumentation and lighting. Since the 1990s, transoral laser
      microsurgery (TLM) has been used as an organ preservation strategy with good
      oncological control and good functional results, although it has not been widely
      used because of its technical difficulty. Recently, transoral robotic surgery
      (TORS) is becoming popular as a new treatment modality for laryngo-pharyngeal
      cancer, and surgical robots are used widely in the world since United States FDA
      approval in 2009. In spite of the global spread of TORS, it has not been approved
      by the Japan FDA, which has led to the development of other low-cost transoral
      surgical techniques in Japan. Transoral videolaryngoscopic surgery (TOVS) was
      developed as a new transoral surgery system for laryngo-pharyngeal lesions to
      address the problems of TLM. In TOVS, a rigid endoscope is used to visualize the
      surgical field instead of a microscope and the advantages of TOVS include the
      wide operative field and working space achieved using the distending laryngoscope
      and videolaryngoscope. Also, with the spread of narrow band imaging (NBI),
      endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD),
      which are widely used for superficial cancers in the gastrointestinal tract, have
      been applied for the superficial laryngo-pharyngeal cancer. Both EMR and ESD are
      performed mainly by gastroenterologists with a sharp dissector and magnifying
      endoscopy (ME)-NBI with minimal surgical margin. Endoscopic laryngo-pharyngeal
      surgery (ELPS) was developed to treat laryngo-pharyngeal superficial cancer by
      modifying the ESD procedure. The concept of ELPS is the same as that of ESD,
      however, the resection procedure is performed by a head and neck surgeon with
      both hands using a ME-NBI and rigid curved laryngo-pharyngoscope. These four
      procedures are low cost with similar oncological and functional outcomes to TORS.
      TORS may be less expensive than chemoradiotherapy, but the number of hospitals
      that can afford da Vinci surgical systems is limited. Even in the era of robotic
      surgery, these four procedures will be good options for laryngo-pharyngeal
      cancer. 

PMID- 26298234
TI  - Differential embryotoxicity of the organic pollutants in rural and urban air
      particles.
AB  - Airborne particulate matter (PM) is a recognized risk factor for human
      populations. Here we assessed the toxic potential of the organic constituents
      from PM collected in urban and rural sites during warm and cold periods of
      2012/2013, and fractionated into 6 size fractions. The finest PM fraction (<0.5
      MUm) showed the highest biological activity (dioxin-like activity and fish
      embryotoxicity) in all samples, and the maximal activity was observed in rural
      samples from the cold period. Zebrafish embryo transcriptome analysis showed a
      strong induction of the AhR signaling pathway correlated to PAH concentrations.
      Oxidative stress-related genes and pancreatic and eye-lens gene markers appeared
      de-regulated in embryos exposed to urban extracts, whereas exposure to rural
      extracts affected genes implicated in basic cellular functions. The observed
      effects can be directly related to air pollution-related human disorders,
      suggesting different potential adverse outcomes for human populations exposed to
      air pollution from specific sources. 

PMID- 26298236
TI  - Successful retrograde percutaneous coronary intervention to a right coronary
      ostium agenesis via an extremely tortuous epicardial collateral.

PMID- 26298235
TI  - Calcified nodule: a double paradox on coronary imaging.

PMID- 26298237
TI  - Very late metallic stent malapposition and in-stent restenosis treated with a
      bioresorbable scaffold: a novel alternative for an old problem.

PMID- 26298238
TI  - A suspicious calcium spike.

PMID- 26298239
TI  - Unexpected reason for a persistent cough: carotid artery pseudoaneurysm with
      arteriovenous fistula.

PMID- 26298240
TI  - High serum lactate level in cranial meningioma resection: A case report.
AB  - BACKGROUND: Peri-operative elevated serum lactate could be a sign of high risk of
      morbidity among affected patients. However, this finding can be self-limiting and
      with no consequences in some conditions. CASE PRESENTATION: We present a case of
      transient elevated serum lactate level in a 33 year old man that underwent a
      cranial meningioma resection. The patient had an elevation of serum lactate
      levels peri-operatively, with a spontaneous gradual decline in the serum lactate
      five hours post-operatively. The patient had an otherwise uncomplicated post
      operative course and was discharged home on the fifth post-operative day.
      CONCLUSION: Elevation in serum lactate level during a large meningioma resection
      could be transient and may not result in morbidity.

PMID- 26298241
TI  - Pseudotumor in the temporomandibular joint: A case report.
AB  - INTRODUCTION: Neoplastic disease in the temporomandibular joint (TMJ) is a rare
      condition and is difficult to differentiate from temporomandibular disorders
      (TMD) based on symptoms and simple X-ray examinations. Potential differential
      diagnoses include synovial chondromatosis and pseudotumor, both of which are also
      relatively rare in the TMJ. PRESENTATION OF CASE: We report a case of pseudotumor
      of the TMJ that was difficult to differentiate from synovial chondromatosis in a
      71-year-old woman with a chief complaint of pain in the left TMJ. MRI of the
      right TMJ initially led to diagnosis of synovial chondromatosis. Extirpation of
      the lesion was performed under general anesthesia. Histopathological findings of
      the resected specimen revealed inflammatory granulation tissue without cellular
      atypism. DISCUSSION: The pathological findings for the resected specimen were
      compatible with pseudotumor of the TMJ. These findings were not supportive of
      synovial chondromatosis or other tumor diseases. CONCLUSION: This case
      illustrates the importance of careful examination of a mass lesion in the TMJ for
      differentiation from other TMJ-related diseases.

PMID- 26298242
TI  - A rare case of penis agenesis (Aphallia) with associated multiple urogenital
      anomalies.
AB  - The penis as a component of external genitalia, takes part in fertility, urinary
      and psychosexual structure of males with its complex character. We report a case
      of penis agenesis with associated left renal agenesis, left superior segment
      ureteral agenesis, prostate agenesis, left ureterocele, right vesicoureteral
      reflux and high urethrorectal communication above the rectal sphincter. The
      patient refused any surgical intervention because of his religious beliefs. 

PMID- 26298243
TI  - Suprameatal extension of retrosigmoid approach for microvascular decompression of
      trigeminal nerve: Case report.
AB  - INTRODUCTION: Trigeminal neuralgia is produced in a significant number of cases
      by vascular compression at the level of cisternal segment of the nerve at the
      entry of the pons. It is common to find superior cerebellar artery (SCA)
      responsible for this compression. The retrosigmoid approach (RA), with asterional
      craniectomy, clearly exposes the cisternal portion of the trigeminal nerve (TN).
      PRESENTATION OF CASE: We describe in this case report how vessels at the
      trigeminal pore level known as "Meckel's segment" can compress the TN. This
      situation is unusual. One of the reasons why the compression of this Meckel's
      segment level could be overlooked is a suprameatal tubercle (ST) prominence that
      would prevent trigeminal pore visualization through retrosigmoid approach.
      DISCUSSION: The suprameatal extension of this approach has been described for
      other purposes, especially in tumors invading Meckel's cave resection. We could
      not find publications for the use of the resection of the suprameatal tubercle in
      the retrosigmoid approach for microvascular decompression of the trigeminal
      neuralgia. CONCLUSION: Microvascular decompression of the TN is an effective
      treatment for trigeminal neuralgia, however in some cases, in which vascular
      compression is not evident when exploring the cerebellopontine angle, it is
      important to note that association of a prominent ST can hide a vascular
      compression of the nerve in this region.

PMID- 26298244
TI  - Management of complication after breast augmentation with methacrylate.
AB  - INTRODUCTION: Several alloplastic biomaterials are available for injection to the
      breast, nevertheless not all of them are approved for biomedical use. Although in
      North America and Western Europe experience with synthetic biomaterials for
      breast augmentation is very limited, migratory streams might expose physicians
      worldwide to manage the related complications of these procedures. The aim of
      this study was to share with other surgeons the case of a patient presenting
      complications after breast augmentation with an unknown synthetic substance
      containing methacrylate. PRESENTATION OF CASE: A 33-years old Asian woman
      presented to our Institution with breast deformities, lumps and chest pain. The
      patient referred previous breast injection "with hospital fat" performed in China
      six years before. She was not aware about the details of the procedure, and
      language barriers limited communication. Clinical examination and ultrasounds
      revealed the irregular distribution of an unknown substance in both breasts. The
      material was surgically removed and replaced in the same session with
      polyurethane implants. Chemical analysis revealed the presence of methacrylate.
      DISCUSSION: With a growing demand for non-invasive cosmetic surgery, has been
      reported a growing population of untrained and unlicensed personnel performing
      cosmetic surgery in many countries where there are no laws that restrict the use
      of cosmetic procedures to physicians with appropriate training and with approved
      materials. Surgical removal of this substances can be extremely challenging and
      an open procedure with surgical debridement is recommended. CONCLUSION: Breast
      augmentation with non-absorbable biomaterials can lead to severe complications,
      in particular for patients intending to breastfeed.

PMID- 26298245
TI  - Significant concentration changes of chemical components of PM1 in the Yangtze
      River Delta area of China and the implications for the formation mechanism of
      heavy haze-fog pollution.
AB  - Since the winter season of 2013, a number of persistent haze-fog events have
      occurred in central-eastern China. Continuous measurements of the chemical and
      physical properties of PM1 at a regional background station in the Yangtze River
      Delta area of China from 16 Nov. to 18 Dec., 2013 revealed several haze-fog
      events, among which a heavy haze-fog event occurred between 6 Dec. and 8 Dec. The
      mean concentration of PM1 was 212MUgm(-3) in the heavy haze-fog period, which was
      about 10 times higher than on clean days and featured a peak mass concentration
      that reached 298MUgm(-3). Organics were the largest contributor to the dramatic
      rise of PM1 on heavy haze-fog days (average mass concentration of 86MUgm(-3)),
      followed by nitrate (58MUgm(-3)), sulfate (35MUgm(-3)), ammonium (29MUgm(-3)),
      and chloride (4.0MUgm(-3)). Nitrate exhibited the largest increase (~20 factors),
      associated with a significant increase in NOx. This was mainly attributable to
      increased coal combustion emissions, relative to motor vehicle emissions, and was
      caused by short-distance pollutant transport within surrounding areas. Low
      volatility oxidized organic aerosols (OA) (LV-OOA) and biomass-burning OA (BBOA)
      also increased sharply on heavy haze-fog days, exhibiting an enhanced oxidation
      capacity of the atmosphere and increased emissions from biomass burning. The
      strengthening of the oxidation capacity during the heavy pollution episode, along
      with lower solar radiation, was probably due to increased biomass burning, which
      were important precursors of O3. The prevailing meteorological conditions,
      including low wind and high relative humidity, and short distance transported
      gaseous and particulate matter surrounding of the sampling site, coincided with
      the increased pollutant concentrations mainly from biomass-burning mentioned
      above to cause the persistent haze-fog event in the YRD area. 

PMID- 26298246
TI  - Impact of treated wastewater on organismic biosensors at various levels of
      biological organization.
AB  - Relating the treated wastewater quality and its impact on organismic biosensors
      (Prussian carp, Carassius gibelio and earthworm, Eisenia fetida) was the main
      objective of the study. The impact on health status of fish living downstream,
      microbiological contamination and antimicrobial resistance, fish tissue
      structure, blood biochemistry, oxidative stress, genotoxic effects, as well as
      multixenobiotic resistance mechanism (MXR) was assessed. Treated wastewater
      discharged from the WWTP modified the environmental parameters and xenobiotic
      concentrations of the receiving surface waters. Potential bacterial pathogens
      from fish and respective waters were found in relatively low numbers, although
      they comprised aeromonads with a zoonotic potential. High resistance profiles
      were determined towards the tested antimicrobial compounds, mostly
      sulfamethoxazole and erythromycin. Histopathology primarily revealed gill
      lamellar fusion and reduction of interlamellar spaces of effluent fish. A
      significant increase in plasma values of urea, total proteins, albumins and
      triglycerides and a significant decrease in the activity of plasma superoxide
      dismutase were noted in carp from the effluent-receiving canal. Micronucleus test
      did not reveal significant differences between the examined groups, but a higher
      frequency of erythrocyte nuclear abnormalities was found in fish sampled from the
      effluent-receiving canal. Earthworms indicated to the presence of MXR inhibitors
      in water and sludge samples, thus proving as a sensitive sentinel organism for
      environmental pollutants. The integrative approach of this study could serve as a
      guiding principle in conducting evaluations of the aquatic habitat health in
      complex bio-monitoring studies. 

PMID- 26298247
TI  - Fecal pollution source tracking toolbox for identification, evaluation and
      characterization of fecal contamination in receiving urban surface waters and
      groundwater.
AB  - The quality of surface waters/groundwater of a geographical region can be
      affected by anthropogenic activities, land use patterns and fecal pollution
      sources from humans and animals. Therefore, the development of an efficient fecal
      pollution source tracking toolbox for identifying the origin of the fecal
      pollution sources in surface waters/groundwater is especially helpful for
      improving management efforts and remediation actions of water resources in a more
      cost-effective and efficient manner. This review summarizes the updated knowledge
      on the use of fecal pollution source tracking markers for detecting, evaluating
      and characterizing fecal pollution sources in receiving surface waters and
      groundwater. The suitability of using chemical markers (i.e. fecal sterols,
      fluorescent whitening agents, pharmaceuticals and personal care products, and
      artificial sweeteners) and/or microbial markers (e.g. F+RNA coliphages, enteric
      viruses, and host-specific anaerobic bacterial 16S rDNA genetic markers) for
      tracking fecal pollution sources in receiving water bodies is discussed. In
      addition, this review also provides a comprehensive approach, which is based on
      the detection ratios (DR), detection frequencies (DF), and fate of potential
      microbial and chemical markers. DR and DF are considered as the key criteria for
      selecting appropriate markers for identifying and evaluating the impacts of fecal
      contamination in surface waters/groundwater. 

PMID- 26298248
TI  - Phototransformation of sulfamethoxazole under simulated sunlight: Transformation
      products and their antibacterial activity toward Vibrio fischeri.
AB  - Sulfamethoxazole (SMX) is a bacteriostatic antibiotic ubiquitously found in the
      aquatic environment. Since conventional biological wastewater treatment is not
      efficient to remove SMX, photolysis in natural waters can represent an important
      transformation pathway. It was recently shown that SMX transformation products
      can retain antibiotic activity. Therefore, it is crucial to better understand
      photochemical processes occurring in natural water just as the formation of
      active transformation products (TPs). During long-term SMX photolysis experiments
      (one week), nine TPs were identified by reference standards. Moreover, five
      further TPs of photodecomposition of SMX were found. For the first time, a TP
      with m/z 271 [M+H](+) was observed during photolysis and tentatively confirmed as
      4,x-dihydroxylated SMX. The DOC mass balance clearly showed that only around 5 to
      10% were mineralized during the experiment emphasizing the need to elucidate the
      fate of TPs. Bacterial bioassays confirmed that the mixture retains its
      antibiotic toxicity toward luminescence (24h) and that there is no change over
      the treatment time on EC50. In contrast, growth inhibition activity was found to
      slightly decrease over the irradiation time. However, this decrease was not
      proportional to the transformation of the parent compound SMX. 

PMID- 26298249
TI  - Impacts of climate and land use changes on the hydrological and erosion processes
      of two contrasting Mediterranean catchments.
AB  - The impacts of climate and land use changes on streamflow and sediment export
      were evaluated for a humid (Sao Lourenco) and a dry (Guadalupe) Mediterranean
      catchment, using the SWAT model. SWAT was able to produce viable streamflow and
      sediment export simulations for both catchments, which provided a baseline for
      investigating climate and land use changes under the A1B and B1 emission
      scenarios for 2071-2100. Compared to the baseline scenario (1971-2000), climate
      change scenarios showed a decrease in annual rainfall for both catchments (humid:
      -12%; dry: -8%), together with strong increases in rainfall during winter. Land
      use changes were derived from a socio-economic storyline in which traditional
      agriculture is replaced by more profitable land uses (i.e. corn and commercial
      forestry at the humid site; sunflower at the dry site). Climate change
      projections showed a decrease in streamflow for both catchments, whereas sediment
      export decreased only for the Sao Lourenco catchment. Land use changes resulted
      in an increase in streamflow, but the erosive response differed between
      catchments. The combination of climate and land use change scenarios led to a
      reduction in streamflow for both catchments, suggesting a domain of the climatic
      response. As for sediments, contrasting results were observed for the humid (A1B:
      -29%; B1: -22%) and dry catchment (A1B: +222%; B1: +5%), which is mainly due to
      differences in the present-day and forecasted vegetation types. The results
      highlight the importance of climate-induced land-use change impacts, which could
      be similar to or more severe than the direct impacts of climate change alone. 

PMID- 26298250
TI  - Geographic isolation of Escherichia coli genotypes in sediments and water of the
      Seven Mile Creek - A constructed riverine watershed.
AB  - Escherichia coli is used to indicate fecal contamination in freshwater systems
      and is an indicator of the potential presence of human pathogens. However,
      naturalized E. coli strains that persist and grow in the environment confound the
      use of this bacterium as a fecal indicator. Here we examined the spatial and
      temporal distribution of E. coli in water and sediments of the Seven Mile Creek
      (SMC), a constructed, ephemeral watershed. E. coli concentrations showed
      variation by site and date, likely due to changes in temperature and rainfall.
      Horizontal fluorophore enhanced rep-PCR (HFERP) DNA fingerprint analyses
      indicated that E. coli populations were very diverse and consisted of transient
      and naturalized strains, which were especially prevalent in sediment. E. coli
      fingerprints from water and sediment collected in the same year clustered
      together with significant overlap, indicating exchange of strains between
      matrices. Isolates obtained during periods of flow, but not during non-flow
      conditions, clustered together regardless of sample site, indicating that
      transport between sites occurred. Naturalized E. coli strains were found in the
      SMC and strains become geographically isolated and distinct during non-flow
      conditions. Isolates collected during late spring to fall clustered together at
      each site, suggesting that temperature and growth of naturalized strains are
      likely factors affecting population dynamics. Results of this study show that
      newly introduced and naturalized E. coli strains are present in the SMC. Results
      of this study highlight an important concern for resource managers using this
      species for water quality monitoring. 

PMID- 26298251
TI  - Characteristics and sources of polycyclic aromatic hydrocarbons in atmospheric
      aerosols in the Kathmandu Valley, Nepal.
AB  - The Kathmandu Valley in the foothills of the Himalayas, where the capital city of
      Nepal is located, has one of the most serious air pollution problems in the
      world. In this study, total suspended particle (TSP) samples collected over a
      year (April 2013-March 2014) in the Kathmandu Valley were analyzed for
      determining the concentrations of 15 priority particle-bound polycyclic aromatic
      hydrocarbons (PAHs). The TSP and PAH concentrations were extremely high, with
      annual average concentration being 199+/-124MUg/m(3) and 155+/-130ng/m(3),
      respectively, which are comparable to those observed in Asian cities such as
      Beijing and Delhi. The TSP and PAH concentrations varied considerably, with the
      seasonal average concentration being maximal during the post-monsoon season
      followed by, in descending order, the winter, pre-monsoon, and monsoon seasons.
      In the winter and pre-monsoon seasons, ambient TSP and PAH concentrations
      increased because of emissions from brick kilns and the use of numerous small
      generators. Moreover, in the pre-monsoon season, forest fires in the surrounding
      regions influenced the TSP and PAH concentrations in the valley. PAHs with 4 to 6
      rings constituted a predominant proportion (92.3-93.3%) of the total PAHs
      throughout the year. Evaluation of diagnostic molecular ratios indicated that the
      atmospheric PAHs in the Kathmandu Valley originated mainly from diesel and
      biomass combustion. The toxic equivalent quantity (TEQ) of particle phase PAHs
      ranged between 2.74 and 81.5ngTEQ/m(3), which is considerably higher than those
      reported in other South Asian cities, and 2-80 times higher than the World Health
      Organization guideline (1ngTEQ/m(3)). This suggests that ambient PAH levels in
      the Kathmandu Valley pose a serious health risk to its approximately 3.5 million
      residents. 

PMID- 26298252
TI  - HONO and its potential source particulate nitrite at an urban site in North China
      during the cold season.
AB  - Characteristics and transformation of nitrous acid (HONO) and particulate nitrite
      were investigated with high time-resolution field measurements at an urban site
      in Ji'nan, China from Nov. 2013 to Jan. 2014. During the sampling period,
      averages of 0.35ppbv HONO and 2.08MUgm(-3) fine particulate nitrite were
      observed. HONO and particulate nitrite exhibited similar diurnal variation
      patterns but differed in the time at which concentration peaks and valleys
      occurred. Elevated nocturnal HONO concentration peaks were mainly associated with
      primary emissions from vehicle exhaust and secondary formation via heterogeneous
      reactions of NO2. In fresh air masses dominated by vehicle emissions, the average
      HONO/NOx ratio was 0.58%. The nocturnal heterogeneous reactions of NO2
      contributed to about half of the elevated HONO concentration peaks, with the
      conversion rates in the range of 0.05% to 0.96%h(-1). Meanwhile, a large amount
      of particulate nitrite, which greatly exceeded the concentration of the gas-phase
      HONO, was also produced through the heterogeneous reactions of NO2. The large
      yields of particulate nitrite were facilitated by abundant ammonia and
      particulate cations in urban Ji'nan. Notably, in the daytime, particulate nitrite
      acted as a potential source of HONO, especially in conditions of low humidity and
      acidic aerosols, which possibly has subsequent effects on photochemistry in the
      boundary layer. 

PMID- 26298253
TI  - A Multi-Criteria Decision Analysis based methodology for quantitatively scoring
      the reliability and relevance of ecotoxicological data.
AB  - Ecotoxicological data are highly important for risk assessment processes and are
      used for deriving environmental quality criteria, which are enacted for assuring
      the good quality of waters, soils or sediments and achieving desirable
      environmental quality objectives. Therefore, it is of significant importance the
      evaluation of the reliability of available data for analysing their possible use
      in the aforementioned processes. The thorough analysis of currently available
      frameworks for the assessment of ecotoxicological data has led to the
      identification of significant flaws but at the same time various opportunities
      for improvement. In this context, a new methodology, based on Multi-Criteria
      Decision Analysis (MCDA) techniques, has been developed with the aim of analysing
      the reliability and relevance of ecotoxicological data (which are produced
      through laboratory biotests for individual effects), in a transparent
      quantitative way, through the use of expert knowledge, multiple criteria and
      fuzzy logic. The proposed methodology can be used for the production of weighted
      Species Sensitivity Weighted Distributions (SSWD), as a component of the
      ecological risk assessment of chemicals in aquatic systems. The MCDA aggregation
      methodology is described in detail and demonstrated through examples in the
      article and the hierarchically structured framework that is used for the
      evaluation and classification of ecotoxicological data is shortly discussed. The
      methodology is demonstrated for the aquatic compartment but it can be easily
      tailored to other environmental compartments (soil, air, sediments). 

PMID- 26298254
TI  - An environmental management industrial solution for the treatment and reuse of
      mussel wastewaters.
AB  - In the North-West of Spain, the annual production of mussel is 2*10(6)t (35% of
      the world). The industrial thermal treatment of mussels generates between 300 and
      400L/t wastewaters that are continuously disposed into the sea without previous
      treatment and or further reuse. These effluents, relatively rich in organic
      matter (7g glycogen/L and 25g COD/L), contribute to the progressive deterioration
      of the marine ecosystem. We wish to suggest a biotechnological process, based on
      a laboratory optimization and industrial pre-scale trials, to transform these
      industrial effluents into a growth culture medium to produce microbial biomass.
      Furthermore, this biomass is isolated and treated by different optimized
      separation and purification processes to produce several bioproducts: 1) single
      cell protein; 2) cell wall material with a high content in glucans and
      glycoproteins 3) fractions of 1,3-beta-glucans and mannoproteins from yeast cell
      walls hydrolysis; and 4) a potential antioxidant extract. Finally, the authors
      propose a scaled process for its industrial application. In consequence, we
      believe that this work provides an environmentally friendly, eco-designed and
      profitable solution that allows integrating the mussel industry into the
      ecosystem in a sustainable way. 

PMID- 26298255
TI  - A new class of draw solutions for minimizing reverse salt flux to improve forward
      osmosis desalination.
AB  - The applications of forward osmosis (FO) have been hindered because of the lack
      of an optimal draw solution. The reverse salt flux from the draw solution not
      only reduces the water flux but also increases the cost of draw solute
      replenishment. Therefore, in this study, Tergitol NP7 and NP9 with a long
      straight carbon chain and low critical micelle concentration (CMC) were coupled
      with highly charged ethylenediaminetetraacetic acid (EDTA) as an innovative draw
      solution to minimize reverse salt diffusion in FO for the first time. The results
      showed that the lowest reverse salt flux of 0.067 GMH was observed when 0.1M EDTA
      2Na coupled with 15mM NP7 was used as a draw solution and deionized water was
      used as a feed solution in FO mode (active layer facing with the feed solution).
      This is due to the hydrophobic interaction between the tails of NP7 and the FO
      membrane, thus creating layers on the membrane surface and constricting the FO
      membrane pores. Moreover, 1M EDTA-2Na coupled with 15mM NP7 is promising as an
      optimal draw solution for brackish water and sea water desalination. Average
      water fluxes of 7.68, 6.78, and 5.95 LMH were achieved when brackish water was
      used as a feed solution (5, 10, and 20g/L NaCl), and an average water flux of
      3.81 LMH was achieved when sea water was used as a feed solution (35g/L NaCl).
      The diluted draw solution was recovered using a nanofiltration (NF-TS80) membrane
      with a high efficiency of 95% because of the high charge and large size of the
      draw solution. 

PMID- 26298256
TI  - Characteristics of maize biochar with different pyrolysis temperatures and its
      effects on organic carbon, nitrogen and enzymatic activities after addition to
      fluvo-aquic soil.
AB  - In this study, the characteristics of maize biochar produced at different
      pyrolysis temperatures (300, 450 and 600 degrees C) and its effects on organic
      carbon, nitrogen and enzymatic activities after addition to fluvo-aquic soil were
      investigated. As pyrolysis temperature increased, ash content, pH, electrical
      conductivity, surface area, pore volume and aromatic carbon content of biochar
      increased while yield, ratios of oxygen:carbon and hydrogen: carbon and alkyl
      carbon content decreased. During incubation, SOC, total N, and ammonium-N
      contents increased in all biochar-amended treatments compared with the urea
      treatment; however, soil nitrate-N content first increased and then decreased
      with increasing pyrolysis temperature of the applied biochar. Extracellular
      enzyme activities associated with carbon transformation first increased and then
      decreased with biochars pyrolyzed at 450 and 600 degrees C. Protease activity
      markedly increased with increased pyrolysis temperatures, whereas pyrolysis
      temperature had limited effect on soil urease activity. The results indicated
      that the responses of extracellular enzymes to biochar were dependent on the
      pyrolysis temperature, the enzyme itself and incubation time as well. 

PMID- 26298257
TI  - Value added liquid products from waste biomass pyrolysis using pretreatments.
AB  - Douglas fir wood, a forestry waste, was attempted to be converted into value
      added products by pretreatments followed by pyrolysis. Four different types of
      pretreatments were employed, namely, hot water treatment, torrefaction, sulphuric
      acid and ammonium phosphate doping. Subsequently, pyrolysis was done at 500
      degrees C and the resulting bio-oils were analysed for their chemical composition
      using Karl Fischer titration, thermogravimetry, ion exchange, and gas
      chromatography. Pretreatment with acid resulted in the highest yield of bio-oil
      (~60%). The acid and salt pretreatments were responsible for drastic reduction in
      the lignin oligomers and enhancement of water content in the pyrolytic liquid.
      The quantity of xylose/mannose reduced as a result of pretreatments. Although,
      the content of fermentable sugars remained similar across all the pretreatments,
      the yield of levoglucosan increased. Pretreatment of the biomass with acid
      yielded the highest amount of levoglucosan in the bio-oil (13.21%). The acid and
      salt pretreatments also elevated the amount of acetic acid in the bio-oils.
      Addition of acid and salt to the biomass altered the interaction of cellulose
      lignin in the pyrolysis regime. Application of pretreatments should be based on
      the intended end use of the liquid product having a desired chemical composition.

PMID- 26298258
TI  - Levels and predictors of persistent organic pollutants in an adult population
      from four Spanish regions.
AB  - This research aimed to assess serum concentrations of a group of persistent
      organic pollutants (POPs) in a sample of adults recruited in four different
      regions from Spain and to assess socio-demographic, dietary, and lifestyle
      predictors of the exposure. The study population comprised 312 healthy adults
      selected from among controls recruited in the MCC-Spain multicase-control study.
      Study variables were collected using standardized questionnaires, and pollutants
      were analyzed by means of gas chromatography with electron capture detection.
      Multivariable analyses were performed to identify predictors of log-transformed
      pollutant concentrations, using combined backward and forward stepwise multiple
      linear regression models. Detection rates ranged from 89.1% (hexachlorobenzene,
      HCB) to 93.6% (Polychlorinated biphenyl-153 [PCB-153]); p,p'
      dichlorodiphenyldichloroethylene (p,p'-DDE) showed the highest median
      concentrations (1.04ng/ml), while HCB showed the lowest (0.24ng/ml). In the
      multivariable models, age was positively associated with HCB, p,p'-DDE, and PCB
      180. BMI was associated positively with p,p'-DDE but negatively with PCB-138.
      Total accumulated time residing in an urban area was positively associated with
      PCB-153 concentrations. The women showed higher HCB and lower p,p'-DDE
      concentrations versus the men. Notably, POP exposure in our study population was
      inversely associated with the breastfeeding received by participants and with the
      number of pregnancies of their mothers but was not related to the participants'
      history of breastfeeding their children or parity. Smoking was negatively
      associated with HCB and PCB-153 concentrations. Consumption of fatty foods,
      including blue fish, was in general positively associated with POP levels.
      Although POP environmental levels are declining worldwide, there is a need for
      the continuous monitoring of human exposure in the general population. The
      results of the present study confirm previous findings and point to novel
      predictors of long-term exposure to persistent organic pollutants. 

PMID- 26298259
TI  - Career choice and future plan of Chinese 8-year stomatology medical doctor
      program students.
AB  - BACKGROUND: This elite education reform that commenced in 2001 aims to improve
      the quality of Chinese dentists. It is expected to be one of the biggest drivers
      that lead dental education of China to a new stage. The authors identified and
      analyzed the perspectives of Chinese 8-year stomatology medical doctor (SMD)
      program students toward their career choice and future plan. METHODS: The data
      from a self-administered questionnaire (4 items regarding career choice and 6
      items about future plan), administered to 87 8-year SMD program students from the
      School of Stomatology, Peking University, Beijing, China, were used. The authors
      performed a comparison of the students of different sexes and home locations
      using the Chi-square test. RESULTS: Of the students, 34.5% indicated
      interpersonal motives as the reason to choose the 8-year SMD program, and only
      52.9% thought that they had made good choices. The top three popular careers were
      those of prosthodontists (20.7%), oral surgeons (14.9%), and orthodontists
      (13.8%). The majority of students preferred first-tier cities (85.7%) and
      university hospitals (71.3%). CONCLUSION: In China, most 8-year S.M.D students
      would like to work as clinical dentists of university hospitals in first-tier
      cities. The top three career choices of graduates would be prosthodontists, oral
      surgeons, and orthodontists.

PMID- 26298260
TI  - Overcoming the barriers of osteoporosis treatment--a better route and a longer
      use.

PMID- 26298261
TI  - Quantitative response relationships between degradation rates and functional
      genes during the degradation of beta-cypermethrin in soil.
AB  - In the present study, the degradation mechanisms of beta-cypermethrin and its
      metabolites in soil were explored through the quantitative response relationships
      between the degradation rates and related functional genes. We found that the
      degradation rate of beta-cypermethrin was rapid in unsterilized soil but not in
      sterilized soil, which indicated that the degradation process is microbially
      based. Moreover, three metabolites (3-phenoxybenzoic acid, phenol and
      protocatechuic acid) were detected during the degradation process and used to
      identify the degradation pathway and functional genes related to the degradation
      process. The key rate-limiting functional genes were pytH and pobA, and the
      relative contributions of these genes to the degradation process were examined
      with a path analysis. The path analysis revealed that the genes pobA and pytH had
      the greatest direct effects on the degradation of beta-cypermethrin (pobA), alpha
      cypermethrin (pobA), theta-cypermethrin (pytH) and 3-phenoxybenzoic acid (pytH). 

PMID- 26298262
TI  - Mechanism of protodesorption-exchange of heavy metal cations for protons in a
      heterophase system of H2O-H2SO4-MSO4-cellulose sorbent.
AB  - The influence of pH on the distribution of metal cations [Cd(II), Cu(II), Fe(II),
      Ni(II), Zn(II)] in a four-component heterophase system (H2O-H2SO4-MSO4-cellulose
      sorbent) was studied. Protodesorption of metal cations was studied with indicator
      and constant quantities of [MSO4] salts and constant solvent-sorbent ratio.
      Linear dependence lgKDM2+=f(rN) with tgalpha=1/2 of the KDM2+ metal ions
      distribution coefficients from the acidity of the aqueous phase is observed in
      logarithmic coordinates. Depression of the exponent corresponding to proton
      involvement in protodesorption from 2 (theory) to 0.5 (experiment) indicates that
      anions of the aqueous phase are involved in the process of exchange of metal
      cation for proton on the anionic centers of the sorbent, which corresponds to
      participation of the salt and acid components of the system in molecular non
      dissociated form in an equivalent proportion H2SO4/MSO4=1/1. Different behavior
      of the salt and acid components in ion exchange of cations for cations and
      cations for protons is due to the differences in the constraint coefficients of
      their molecular and ionic forms which must be taken into consideration in
      equations describing thermodynamics of the interphase exchange. 

PMID- 26298263
TI  - Occurrence and estrogenic potency of eight bisphenol analogs in sewage sludge
      from the U.S. EPA targeted national sewage sludge survey.
AB  - As health concerns over bisphenol A (BPA) in consumer products are mounting, this
      weak estrogen mimicking compound is gradually being replaced with structural
      analogs, whose environmental occurrence and estrogen risks are not well
      understood yet. We used high performance liquid chromatography-tandem mass
      spectrometry (HPLC-MS/MS) to determine the concentrations of eight bisphenol
      analogs in 76 sewage sludge samples collected by the U.S. Environmental
      Protection Agency (EPA) in 2006/2007 from 74 wastewater treatment plants (WWTPs)
      in 35 states. Bisphenols were detected at the following concentration ranges
      (ng/g dry weight) and detection frequencies: BPA (6.5-4700; 100%); bisphenol S
      (BPS; <1.79-1480; 84%); bisphenol F (BPF; <1.79-242; 68%); bisphenol AF (BPAF;
      <1.79-72.2; 46%); bisphenol P (BPP; <1.79-6.42; <5%), bisphenol B (BPB; <1.79
      5.60; <5%), and bisphenol Z (BPZ; <1.79--66.7; <5%). Bisphenol AP (BPAP) was not
      detected in any of the samples (<1.79 ng/g dw). Concentrations of BPA in sewage
      sludge were an order of magnitude higher than those reported in China but similar
      to those in Germany. The calculated 17beta-estradiol equivalents (E2EQ) of
      bisphenols present in sludge samples were 7.74 (0.26-90.5) pg/g dw, which were
      three orders of magnitude lower than the estrogenic activity contributed by
      natural estrogens present in the sludge. The calculated mass loading of
      bisphenols through the disposal of sludge and wastewater was <0.02% of the total
      U.S. production. As the usage of BPA is expected to decline further,
      environmental emissions of BPS, BPF, and BPAF are likely to increase in the
      future. This study establishes baseline levels and estrogenic activity of diverse
      bisphenol analogs in sewage sludge.

PMID- 26298264
TI  - The centralized control of elemental mercury emission from the flue gas by a
      magnetic rengenerable Fe-Ti-Mn spinel.
AB  - A magnetic Fe-Ti-Mn spinel was developed to adsorb gaseous Hg(0) in our previous
      study. However, it is currently extremely restricted in the control of Hg(0)
      emission from the flue gas for at least three reasons: sorbent recovery, sorbent
      regeneration and the interference of the chemical composition in the flue gas.
      Therefore, the effect of SO2 and H2O on the adsorption of gaseous Hg(0) on the Fe
      Ti-Mn spinel and the regeneration of spent Fe-Ti-Mn spinel were investigated in
      this study. Meanwhile, the procedure of the centralized control of Hg(0) emission
      from the flue gas by the magnetic Fe-Ti-Mn spinel has been analyzed for
      industrial application. The spent Fe-Ti-Mn spinel can be regenerated by water
      washing followed by the thermal treatment at 450  degrees C with no obvious
      decrease of its ability for Hg(0) capture. Meanwhile, gaseous Hg(0) in the flue
      gas can be remarkably concentrated during the regeneration, facilitating its safe
      disposal. Initial pilot test demonstrated that gaseous Hg(0) in the real flue gas
      can be concentrated at least 100 times by the Fe-Ti-Mn spinel. Therefore, Fe-Ti
      Mn spinel was a novel magnetic regenerable sorbent, which can be used for the
      centralized control of Hg(0) emission from the flue gas.

PMID- 26298265
TI  - Cushing's syndrome with adrenal suppression and masked hyperandrogenism by high
      dose medroxyprogesterone acetate for treatment of endometrial cancer in a young
      woman with polycystic ovarian syndrome.

PMID- 26298266
TI  - Revisiting theoretical and causal explanations for the bilingual advantage in
      executive functioning.

PMID- 26298267
TI  - On the belief that the cognitive exercise associated with the acquisition of a
      second language enhances extra-linguistic cognitive functions: Is "Type-I
      incompetence" at work here?

PMID- 26298268
TI  - Still waiting for real answers.

PMID- 26298269
TI  - Isolation and Characterization of Multi-Metal-Resistant Halomonas sp. MG from
      Tamil Nadu Magnesite Ore Soil in India.
AB  - The aim of the study was to isolate and characterize potential multi-metal
      resistant bacteria from ore soils. A total of three bacteria were isolated and
      assayed for resistance to arsenic (As), copper (Cu), and lead (Pb). Isolate
      Halomonas sp. MG exhibited maximum resistance to 1000 mg Pb/L, 800 mg As/L, and
      500 mg Cu/L and it was identified as Halomonas sp. based on the partial 16S rDNA
      sequences. The metal(loid)s resistance mechanisms were further confirmed by
      amplification of arsC (As) copAU (Cu), and pbrT (Pb) genes. Biological
      transmission electron micrographs and XRD studies showed that the isolate
      Halomonas sp. MG transformed and/or biomineralized the metals either
      intracellularly or extracellularly. These results suggest that the isolate could
      be used as a potential candidate for the bioremediation of As, Cu, and Pb.

PMID- 26298270
TI  - Simple accurate mathematical models of blood HbO2 and HbCO2 dissociation curves
      at varied physiological conditions: evaluation and comparison with other models.
AB  - PURPOSE: Equations for blood oxyhemoglobin (HbO2) and carbaminohemoglobin (HbCO2)
      dissociation curves that incorporate nonlinear biochemical interactions of oxygen
      and carbon dioxide with hemoglobin (Hb), covering a wide range of physiological
      conditions, are crucial for a number of practical applications. These include the
      development of physiologically-based computational models of alveolar-blood and
      blood-tissue O2-CO2 transport, exchange, and metabolism, and the analysis of
      clinical and in vitro data. METHODS AND RESULTS: To this end, we have revisited,
      simplified, and extended our previous models of blood HbO2 and HbCO2 dissociation
      curves (Dash and Bassingthwaighte, Ann Biomed Eng 38:1683-1701, 2010), validated
      wherever possible by available experimental data, so that the models now
      accurately fit the low HbO2 saturation (SHbO2) range over a wide range of values
      of PCO2, pH, 2,3-DPG, and temperature. Our new equations incorporate a novel PO2
      dependent variable cooperativity hypothesis for the binding of O2 to Hb, and a
      new equation for P50 of O2 that provides accurate shifts in the HbO2 and HbCO2
      dissociation curves over a wide range of physiological conditions. The accuracy
      and efficiency of these equations in computing PO2 and PCO2 from the SHbO2 and
      SHbCO2 levels using simple iterative numerical schemes that give rapid
      convergence is a significant advantage over alternative SHbO2 and SHbCO2 models.
      CONCLUSION: The new SHbO2 and SHbCO2 models have significant computational
      modeling implications as they provide high accuracy under non-physiological
      conditions, such as ischemia and reperfusion, extremes in gas concentrations,
      high altitudes, and extreme temperatures.

PMID- 26298271
TI  - How accurate is accident data in road safety research? An application of vehicle
      black box data regarding pedestrian-to-taxi accidents in Korea.
AB  - Recently, the introduction of vehicle black box systems or in-vehicle video event
      data recorders enables the driver to use the system to collect more accurate
      crash information such as location, time, and situation at the pre-crash and
      crash moment, which can be analyzed to find the crash causal factors more
      accurately. This study presents the vehicle black box system in brief and its
      application status in Korea. Based on the crash data obtained from the vehicle
      black box system, this study analyzes the accuracy of the crash data collected
      from existing road crash data recording method, which has been recorded by police
      officers based on accident parties' statements or eyewitness's account. The
      analysis results show that the crash data observed by the existing method have an
      average of 84.48m of spatial difference and standard deviation of 157.75m as well
      as average 29.05min of temporal error and standard deviation of 19.24min.
      Additionally, the average and standard deviation of crash speed errors were found
      to be 9.03km/h and 7.21km/h, respectively. 

PMID- 26298272
TI  - Analysis of railroad tank car releases using a generalized binomial model.
AB  - The United States is experiencing an unprecedented boom in shale oil production,
      leading to a dramatic growth in petroleum crude oil traffic by rail. In 2014,
      U.S. railroads carried over 500,000 tank carloads of petroleum crude oil, up from
      9500 in 2008 (a 5300% increase). In light of continual growth in crude oil by
      rail, there is an urgent national need to manage this emerging risk. This need
      has been underscored in the wake of several recent crude oil release incidents.
      In contrast to highway transport, which usually involves a tank trailer, a crude
      oil train can carry a large number of tank cars, having the potential for a
      large, multiple-tank-car release incident. Previous studies exclusively assumed
      that railroad tank car releases in the same train accident are mutually
      independent, thereby estimating the number of tank cars releasing given the total
      number of tank cars derailed based on a binomial model. This paper specifically
      accounts for dependent tank car releases within a train accident. We estimate the
      number of tank cars releasing given the number of tank cars derailed based on a
      generalized binomial model. The generalized binomial model provides a
      significantly better description for the empirical tank car accident data through
      our numerical case study. This research aims to provide a new methodology and new
      insights regarding the further development of risk management strategies for
      improving railroad crude oil transportation safety. 

PMID- 26298273
TI  - Effectiveness of virtual classroom training in improving the knowledge and key
      maternal neonatal health skills of general nurse midwifery students in Bihar,
      India: A pre- and post-intervention study.
AB  - BACKGROUND: In 2008-09, the National Health Systems Resource Center of India
      reported overall quality of nurse-midwifery education in Bihar as grossly sub
      optimal. To address this, we implemented a competency-based training using
      virtual classrooms in two general nurse midwives (GNM) schools of Bihar. The
      students from remotely located nursing institutions were now able to see live
      demonstrations of maternal and newborn health (MNH) practices performed by a
      trained faculty on simulation models at instructor location. OBJECTIVE: To
      evaluate the effectiveness of virtual classroom training in improving the MNH
      related skills of the nursing-midwifery students in Bihar, India. DESIGN: This
      study used a pre- and post-intervention design without a control group. SETTINGS:
      Students from two public GNM schools of Bihar. PARTICIPANTS: Final-year students
      from both the GNM schools who have completed their coursework in MNH. METHOD: A
      total of 83 students from selected GNM schools were assessed for their
      competencies in six key MNH practices using objective structured clinical
      examination method prior to intervention. A 72hour standardized training package
      was then implemented in these schools through virtual classroom approach. Post
      intervention, 92 students from the next batch who attended virtual training were
      assessed for the same competencies. RESULTS: The mean student score assessed
      before the intervention was 21.3 (95% CI, 19.9-22.6), which increased to 62.0
      (95% CI, 60.3-63.7) post-intervention. This difference was statistically
      significant. When adjusted for clustering using linear regression analysis, the
      students in post-intervention scored 52.3 (95% CI, 49.4%-55.3%) percentage points
      higher than pre-intervention, and this was statistically significant. CONCLUSION:
      Virtual classroom training was found to be effective in improving knowledge and
      key MNH skills of GNM students in Bihar, India.

PMID- 26298274
TI  - Exploring the environment of clinical baccalaureate nursing students' education
      in Iran; A qualitative descriptive study.
AB  - INTRODUCTION: Today's students are the nurses of tomorrow. They need appropriate
      clinical learning opportunities in order to shape their professional identity,
      attitudes and values. Despite undeniable progresses of nursing education in Iran,
      the quality of the clinical education in Iran is not favorable. There is a need
      to explore the environment of clinical baccalaureate nursing students' education
      for developing, maintaining and enhancing the quality of clinical program.
      METHOD: This is a qualitative study and was conducted based on content analysis
      multimethod design. Data were collected by individual interviews, focus groups
      and direct observations. 54 nursing students and 8 clinical educators from the
      four geographically diverse universities in the Iran composed the study sample. A
      purposive sampling was used. RESULT: Five themes were emerged from data analysis
      including; ambiguity in the nursing care role, routine-based nursing care,
      uncritical and dependent thinking climate, incompetency of clinical educators and
      patient education as important component of nursing. CONCLUSIONS: The findings of
      this study describe a clearer understanding of the real environment of the
      clinical education in Iran. All of themes that emerged from the study play an
      important role in student learning and nursing education. It is crucial to pay
      more attention to reconsider care concept as an operational component of nursing,
      maximize meaningful learning opportunities, reevaluate clinical instructor as
      role models and prepare effective operational plan to combine theoretical and
      evidence based knowledge with clinical practice.

PMID- 26298275
TI  - Roles of CDKN1B in cancer?

PMID- 26298277
TI  - Topography of Place Maps along the CA3-to-CA2 Axis of the Hippocampus.
AB  - We asked whether the structural heterogeneity of the hippocampal CA3-CA2 axis is
      reflected in how space is mapped onto place cells in CA3-CA2. Place fields were
      smaller and sharper in proximal CA3 than in distal CA3 and CA2. The proximodistal
      shift was accompanied by a progressive loss in the ability of place cells to
      distinguish configurations of the same spatial environment, as well as a
      reduction in the extent to which place cells formed uncorrelated representations
      for different environments. The transition to similar representations was
      nonlinear, with the sharpest drop in distal CA3. These functional changes along
      the CA3-CA2 axis mirror gradients in gene expression and connectivity that partly
      override cytoarchitectonic boundaries between the subfields of the hippocampus.
      The results point to the CA3-CA2 axis as a functionally graded system with
      powerful pattern separation at the proximal end, near the dentate gyrus, and
      stronger pattern completion at the CA2 end.

PMID- 26298276
TI  - Neural Population Evidence of Functional Heterogeneity along the CA3 Transverse
      Axis: Pattern Completion versus Pattern Separation.
AB  - Classical theories of associative memory model CA3 as a homogeneous attractor
      network because of its strong recurrent circuitry. However, anatomical gradients
      suggest a functional diversity along the CA3 transverse axis. We examined the
      neural population coherence along this axis, when the local and global spatial
      reference frames were put in conflict with each other. Proximal CA3 (near the
      dentate gyrus), where the recurrent collaterals are the weakest, showed degraded
      representations, similar to the pattern separation shown by the dentate gyrus.
      Distal CA3 (near CA2), where the recurrent collaterals are the strongest,
      maintained coherent representations in the conflict situation, resembling the
      classic attractor network system. CA2 also maintained coherent representations.
      This dissociation between proximal and distal CA3 provides strong evidence that
      the recurrent collateral system underlies the associative network functions of
      CA3, with a separate role of proximal CA3 in pattern separation. 

PMID- 26298278
TI  - (75)As NQR studies on FeAs2.
AB  - (75)As NQR spectra and relaxation times of synthetic and natural FeAs2 samples
      have been studied at variable static magnetic field and temperature. FeAs2 is a
      well understood diamagnetic semiconductor and occurs as the natural mineral
      lollingite in selected ore deposits. We observed a spin-spin relaxation time
      enhancement of up to five in synthetic powders in the presence of a weak external
      static magnetic field. The effect is of interest with regard to signal-to-noise
      ratio improvement for materials characterization applications where broad NQR
      absorption lines are excited with wideband pulse sequences. 

PMID- 26298280
TI  - Development and validation of a direct-comparison method for cardiac (123)I
      metaiodobenzylguanidine washout rates derived from late 3-hour and 4-hour
      imaging.
AB  - PURPOSE: The washout rate (WR) has been used in (123)I-metaiodobenzylguanidine
      (MIBG) imaging to evaluate cardiac sympathetic innervation. However, WR varies
      depending on the time between the early and late MIBG scans. Late scans are
      performed at either 3 or 4 hours after injection of MIBG. The aim of this study
      was to directly compare the WR at 3 hours (WR3h) with the WR at 4 hours (WR4h).
      METHODS: We hypothesized that the cardiac count would reduce linearly between the
      3-hour and 4-hour scans. A linear regression model for cardiac counts at two time
      points was generated. We enrolled a total of 96 patients who underwent planar
      (123)I-MIBG scintigraphy early (15 min) and during the late phase at both 3 and 4
      hours. Patients were randomly divided into two groups: a model-creation group
      (group 1) and a clinical validation group (group 2). Cardiac counts at 15 minutes
      (countearly), 3 hours (count3h) and 4 hours (count4h) were measured. Cardiac
      count4h was mathematically estimated using the linear regression model from
      countearly and count3h. RESULTS: In group 1, the actual cardiac
      count4h/countearly was highly significantly correlated with count3h/countearly (r
      = 0.979). In group 2, the average estimated count4h was 92.8 +/- 31.9, and there
      was no significant difference between this value and the actual count4h (91.9 +/-
      31.9). Bland-Altman analysis revealed a small bias of -0.9 with 95 % limits of
      agreement of -6.2 and +4.3. WR4h calculated using the estimated cardiac count4h
      was comparable to the actual WR4h (24.3 +/- 9.6 % vs. 25.1 +/- 9.7 %, p = ns).
      Bland-Altman analysis and the intraclass correlation coefficient showed that
      there was excellent agreement between the estimated and actual WR4h. CONCLUSION:
      The linear regression model that we used accurately estimated cardiac count4h
      using countearly and count3h. Moreover, WR4h that was mathematically calculated
      using the estimated count4h was comparable to the actual WR4h.

PMID- 26298279
TI  - Important abnormalities of bone mineral metabolism are present in patients with
      coronary artery disease with a mild decrease of the estimated glomerular
      filtration rate.
AB  - Chronic kidney disease (CKD)-mineral and bone disorder (MBD) is characterized by
      increased circulating levels of parathormone (PTH) and fibroblast growth factor
      23 (FGF23), bone disease, and vascular calcification, and is associated with
      adverse outcomes. We studied the prevalence of mineral metabolism disorders, and
      the potential relationship between decreased estimated glomerular filtration rate
      (eGFR) and CKD-MBD in coronary artery disease patients in a cross-sectional study
      of 704 outpatients 7.5 +/- 3.0 months after an acute coronary syndrome. The mean
      eGFR (CKD Epidemiology Collaboration formula) was 75.8 +/- 19.1 ml/min/1.73 m(2).
      Our patients showed lower calcidiol plasma levels than a healthy cohort from the
      same geographical area. In the case of men, this finding was present despite
      similar creatinine levels in both groups and older age of the healthy subjects.
      Most patients (75.6 %) had an eGFR below 90 ml/min/1.73 m(2) (eGFR categories G2
      G5), with 55.3 % of patients exhibiting values of 60-89 ml/min/1.73 m(2) (G2).
      PTH (r = -0.3329, p < 0.0001) and FGF23 (r = -0.3641, p < 0.0001) levels
      inversely correlated with eGFR, whereas calcidiol levels and serum phosphate
      levels did not. Overall, PTH levels were above normal in 34.9 % of patients. This
      proportion increased from 19.4 % in G1 category patients, to 33.7 % in G2
      category patients and 56.6 % in G3-G5 category patients (p < 0.001). In
      multivariate analysis, eGFR and calcidiol levels were the main independent
      determinants of serum PTH. The mean FGF23 levels were 69.9 (54.6-96.2) relative
      units (RU)/ml, and 33.2 % of patients had FGF23 levels above 85.5 RU/ml (18.4 %
      in G1 category patients, 30.0 % in G2 category patients, and 59.2 % in G3-G5
      category patients; p < 0.001). In multivariate analysis, eGFR was the main
      predictor of FGF23 levels. Increased phosphate levels were present in 0.7 % of
      the whole sample: 0 % in G1 category patients, 0.3 % in G2 category patients, and
      2.8 % in G3-G5 category patients (p = 0.011). Almost 90 % of patients had
      calcidiol insufficiency without significant differences among the different
      degrees of eGFR. In conclusion, in patients with coronary artery disease there is
      a large prevalence of increased FGF23 and PTH levels. These findings have an
      independent relationship with decreased eGFR, and are evident at an eGFR of 60-89
      ml/min/1.73 m(2). Then, mild decreases in eGFR must be taken in consideration by
      the clinician because they are associated with progressive abnormalities of
      mineral metabolism. 

PMID- 26298281
TI  - The Choice Between Total Hip Arthroplasty and Arthrodesis in Adolescent Patients:
      A Survey of Orthopedic Surgeons.
AB  - For adolescent patients with end-stage hip disease, the choice between total hip
      arthroplasty (THA) and arthrodesis is complex; the clinical evidence is not
      definitive, and there are difficult trade-offs between clear short-term benefits
      from THA and uncertain long-term risks. We surveyed nearly 700 members of the
      Pediatric Orthopedic Society of North America and the American Association of Hip
      and Knee Surgeons. Respondents chose between a recommendation of THA or
      arthrodesis in four clinical vignettes. A clear majority of surgeons recommended
      THA in two of the vignettes, however opinion was somewhat divided in one vignette
      (overweight adolescent) and deeply divided in another (adolescent destined for
      manual labor job). Across all vignettes, recommendations varied systematically
      according to surgeons' age and their attitudes regarding tradeoffs between life
      stages. 

PMID- 26298282
TI  - Hypoxia and glioblastoma therapy.

PMID- 26298283
TI  - Two step continuous method to synthesize colloidal spheroid gold nanorods.
AB  - This research investigated a two-step continuous process to synthesize colloidal
      suspension of spheroid gold nanorods. In the first step; gold precursor was
      reduced to seed-like particles in the presence of polyvinylpyrrolidone and
      ascorbic acid. In continuous second step; silver nitrate and alkaline sodium
      hydroxide produced various shape and size Au nanoparticles. The shape was
      manipulated through weight ratio of ascorbic acid to silver nitrate by varying
      silver nitrate concentration. The specific weight ratio of 1.35-1.75 grew
      spheroid gold nanorods of aspect ratio ~1.85 to ~2.2. Lower weight ratio of 0.5
      1.1 formed spherical nanoparticle. The alkaline medium increased the yield of
      gold nanorods and reduced reaction time at room temperature. The synthesized gold
      nanorods retained their shape and size in ethanol. The surface plasmon resonance
      was red shifted by ~5 nm due to higher refractive index of ethanol than water.

PMID- 26298285
TI  - Influence of the heterogeneous wettability on capillary trapping in glass-beads
      monolayers: Comparison between experiments and the invasion percolation theory.
AB  - We demonstrated that a change in the surface chemistry, i.e., a change from
      heterogeneous to homogeneous wettability, can dramatically influence capillary
      trapping, i.e., from significant trapping (~5%) to no trapping. Furthermore, the
      displacement process (water displaces air) in glass-beads monolayer with
      heterogeneous wettability shows (i) a heterogeneous morphology and a stochastic
      advancement of the interface in the highly ordered triangular structure, (ii)
      capillary trapping of a broad variety of gas clusters, notably large ganglia-like
      and network-like gas clusters, and (iii) a variation in the contact angle between
      30 degrees  and 100 degrees . In the second part of this paper, we compared the
      experimental results of capillary trapping for the monolayer that possesses a
      heterogeneous wettability with predictions from the invasion percolation theory
      and found excellent agreement, e.g., that the experimental cluster size
      distribution can be described by a universal power-law with an averaged exponent
      tau(exp)=2.06; that is a deviation of 5% from the theoretical value. This
      agreement indicates that capillary trapping within the 2D-monolayer is governed
      by the 3D critical exponent; therefore, the monolayer shows a trapping behavior
      similar to a 3D-porous media. We proposed an analytical approach to calculate the
      mass transfer rate constant using functional relationships predicted by
      percolation theory and compare this result with results derived from empirical
      relationships, which are often used for modelling the dissolution process of
      trapped non-wetting phases.

PMID- 26298284
TI  - Solvothermal synthesis and upconversion properties of about 10 nm orthorhombic
      LuF3: Yb3+, Er3+ rectangular nanocrystals.
AB  - The Yb(3+) and Er(3+) codoped orthorhombic LuF3 rectangular nanocrystals (NCs)
      with the size of about 10nm were synthesized by a facile and effective
      solvothermal process. X-ray diffraction (XRD), transmission electron microscopy
      (TEM), high-resolution transmission electron microscopy (HRTEM), upconversion
      (UC) luminescence spectra and decay curves were used to characterize the
      resulting samples. Compared with YF3 and alpha-NaYF4 NCs, owning the similar size
      and the same doping levels of Yb(3+) ions and Er(3+) ions as LuF3 NCs, the green
      UC emission of LuF3 NCs is 18.7 times and 5.1 times stronger than that of YF3 and
      alpha-NaYF4 NCs respectively; the red UC emission of LuF3 NCs is 13.2 times and
      0.6 times stronger than that of YF3 and alpha-NaYF4 NCs respectively. Under 980
      nm wavelength excitation, the decay curves of both (4)S3/2->(4)I15/2 transition
      and (4)F9/2->(4)I15/2 transition exhibit a single exponential function, resulting
      from the fast energy migrations among Yb(3+) ions caused by the high
      concentration of Yb(3+) ions (20 mol%). Meanwhile, at relatively low power
      density, the slopes of the linear plots between log(I) and log(P) for green UC
      and red UC are 1.7 and 1.9 respectively, which are less than 2 due to the
      quenching of the thermal effect, indicating a two-photon process for them. At
      high power density, the slopes are decreased caused by the saturation effect. In
      addition, we proved the existence of the thermal effect by the pump power
      dependence of the intensity ratio of (2)H11/2->(4)I15/2 transition to (4)S3/2
      >(4)I15/2 transition.

PMID- 26298286
TI  - Advanced and economical ambient drying method for controlled mesopore
      polybenzoxazine-based carbon xerogels: Effects of non-ionic and cationic
      surfactant on porous structure.
AB  - Polybenzoxazine has been successfully synthesized by a facile quasi-solventless
      method and used as a precursor for producing carbon xerogels via an ambient
      drying method, rather than usually used CO2 critical or freeze drying. In this
      work, we aim to study the effect of non-ionic (Synperonic NP30) and cationic
      (CTAB) surfactants on porous structure of polybenzoxazine-based carbon xerogels.
      Of particular interest is the formation of inter-connected structure of
      mesoporous carbon xerogels with mesopore diameters in the range of 15-36 nm by
      using different concentrations of the cationic surfactant. In addition, carbon
      xerogel nanospheres with the size of 50-200 nm are also obtained through the
      emulsion process. The mesopore diameters start to decrease when the carbon
      xerogel nanospheres are formed at the cationic surfactant concentration of equal
      to or exceeding 0.030 M. By using the non-ionic surfactant, the properties of the
      obtained carbon xerogels are shifted from mesoporous materials for the reference
      carbon xerogel (no surfactant added) to microporous materials at higher
      concentrations of the non-ionic surfactant (0.009-0.180 M). The carbon xerogel
      microspheres with the diameter size of about 2.5 MUm are also obtained through
      the emulsion process when the concentration of the non-ionic surfactant is at
      0.180 M.

PMID- 26298287
TI  - Methotrexate modulates the expression of MMP-1 and type 1 collagen in dermal
      fibroblast.
AB  - Methotrexate (MTX), an anti-metabolite and anti-inflammatory drug, has been used
      to effectively manage and prevent keloids, but its mechanism(s) of action has not
      been elucidated. Our study sought to evaluate the effect of MTX on the production
      of key extra cellular matrix components, collagen, and matrix metalloproteinase-1
      (MMP-1), produced by fibroblasts and involved in development of fibrosis. The
      proliferation and viability of cultured human dermal fibroblasts in response to
      different concentrations of MTX were determined using cell counting and MTT
      assay, respectively. Western blot analysis was used to determine the levels of
      both intracellular and secreted type 1 collagen and MMP-1. The results showed no
      significant changes in the proliferation of fibroblasts treated with 50 ng/ml of
      MTX as compared to that of control. Under the same experimental conditions, the
      level of secreted and intracellular type I collagen was markedly reduced and,
      conversely, the level of MMP-1 increased in treated neonatal, adult, and
      hypertrophic scar fibroblasts as compared with those of controls. The possible
      involvement of MTX-induced extracellular signal-regulated kinase 1/2 (ERK1/2)
      pathway in MMP-1 production was also studied and the result showed an increase in
      phosphorylated ERK 1/2 in response to MTX treatment. In summary, the findings of
      this study revealed that MTX significantly reduced collagen production in
      different strains of fibroblasts derived from neonatal, adult, and hypertrophic
      scar tissues, while under the same experimental conditions, it increased the
      expression of MMP-1. As such, our findings validate and identify a potential
      mechanism through which MTX functions as an anti-fibrogenic factor in treating
      fibroproliferative disorders. 

PMID- 26298288
TI  - Effect of anterior cruciate ligament rupture on secondary damage to menisci and
      articular cartilage.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of anterior cruciate
      ligament (ACL) rupture on secondary damage to menisci and articular cartilage.
      METHOD: A total of 366 patients with knee ACL rupture were divided into the
      following six groups based on the time span from the initial injury to ACL
      reconstruction: (1) <1.5months; (2) between 1.5 and three months; (3) between
      three and six months; (4) between six and 12months; (5) between 12 and 24months,
      and (6) >24months. During ACL reconstruction, impairment of meniscal or chondral
      integrity was systematically documented. RESULTS: Of the 366 patients involved in
      this study, meniscal and chondral damage were found in 223 (60.9%) and 75 (20.5%)
      patients, respectively. In addition, the incidence of medial meniscal and
      chondral damage was significantly increased when ACL reconstruction was delayed.
      The incidence of medial meniscal and chondral damage was found to be 6.1 and 9.9
      times higher in patients with a time from initial injury (TFI) of >24months than
      those with a TFI of <1.5months, respectively. CONCLUSION: In this study,
      correlations between secondary damage to the menisci and/or the articular
      cartilage and time after initial injury were found in Chinese population. Our
      data suggested that ACL reconstruction should be performed as early as possible
      after ACL rupture to avoid secondary meniscal and/or chondral damage. It is
      recommended that the best time range for ACL reconstruction is between four and
      six weeks after initial injury.

PMID- 26298289
TI  - AuNP flares-capped mesoporous silica nanoplatform for MTH1 detection and
      inhibition.
AB  - The human mutT homologue MTH1, a nucleotide pool sanitizing enzyme, represents a
      vulnerability factor and an attractive target for anticancer therapy. However,
      there is currently a lack of selective and effective platforms for the detection
      and inhibition of MTH1 in cells. Here, we demonstrate for the first time a gold
      nanoparticle (AuNP) flares-capped mesoporous silica nanoparticle (MSN)
      nanoplatform that is capable of detecting MTH1 mRNA and simultaneously
      suppressing MTH1 activity. The AuNP flares are made from AuNPs that are
      functionalized with a dense shell of MTH1 recognition sequences hybridized to
      short cyanine (Cy5)-labeled reporter sequences and employed to seal the pores of
      MSN to prevent the premature MTH1 inhibitors (S-crizotinib) release. Just like
      the pyrotechnic flares that produce brilliant light when activated, the resulting
      AuNP flares@MSN (S-crizotinib) undergo a significant burst of red fluorescence
      enhancement upon MTH1 mRNA binding. This hybridization event subsequently induces
      the opening of the pores and the release of S-crizotinib in an mRNA-dependent
      manner, leading to significant cytotoxicity in cancer cells and improved
      therapeutic response in mouse xenograft models. We anticipate that this
      nanoplatform may be an important step toward the development of MTH1-targeting
      theranostics and also be a useful tool for cancer phenotypic lethal anticancer
      therapy. 

PMID- 26298290
TI  - Prion protein "gamma-cleavage": characterizing a novel endoproteolytic processing
      event.
AB  - The cellular prion protein (PrP(C)) is a ubiquitously expressed protein of
      currently unresolved but potentially diverse function. Of putative relevance to
      normal biological activity, PrP(C) is recognized to undergo both alpha- and beta
      endoproteolysis, producing the cleavage fragment pairs N1/C1 and N2/C2,
      respectively. Experimental evidence suggests the likelihood that these processing
      events serve differing cellular needs. Through the engineering of a C-terminal c
      myc tag onto murine PrP(C), as well as the selective use of a far-C-terminal anti
      PrP antibody, we have identified a new PrP(C) fragment, nominally 'C3', and
      elaborating existing nomenclature, 'gamma-cleavage' as the responsible
      proteolysis. Our studies indicate that this novel gamma-cleavage event can occur
      during transit through the secretory pathway after exiting the endoplasmic
      reticulum, and after PrP(C) has reached the cell surface, by a matrix
      metalloprotease. We found that C3 is GPI-anchored like other C-terminal and full
      length PrP(C) species, though it does not localize primarily at the cell surface,
      and is preferentially cleaved from an unglycosylated substrate. Importantly, we
      observed that C3 exists in diverse cell types as well as mouse and human brain
      tissue, and of possible pathogenic significance, gamma-cleavage may increase in
      human prion diseases. Given the likely relevance of PrP(C) processing to both its
      normal function, and susceptibility to prion disease, the potential importance of
      this previously underappreciated and overlooked cleavage event warrants further
      consideration. 

PMID- 26298292
TI  - Organization of microtubule assemblies in Dictyostelium syncytia depends on the
      microtubule crosslinker, Ase1.
AB  - It has long been known that the interphase microtubule (MT) array is a key
      cellular scaffold that provides structural support and directs organelle
      trafficking in eukaryotic cells. Although in animal cells, a combination of
      centrosome nucleating properties and polymer dynamics at the distal microtubule
      ends is generally sufficient to establish a radial, polar array of MTs, little is
      known about how effector proteins (motors and crosslinkers) are coordinated to
      produce the diversity of interphase MT array morphologies found in nature. This
      diversity is particularly important in multinucleated environments where multiple
      MT arrays must coexist and function. We initiate here a study to address the
      higher ordered coordination of multiple, independent MT arrays in a common
      cytoplasm. Deletion of a MT crosslinker of the MAP65/Ase1/PRC1 family disrupts
      the spatial integrity of multiple arrays in Dictyostelium discoideum, reducing
      the distance between centrosomes and increasing the intermingling of MTs with
      opposite polarity. This result, coupled with previous dynein disruptions suggest
      a robust mechanism by which interphase MT arrays can utilize motors and
      crosslinkers to sense their position and minimize overlap in a common cytoplasm. 

PMID- 26298293
TI  - A role for retromer in hepatitis C virus replication.
AB  - Hepatitis C virus (HCV) has infected over 170 million people worldwide.
      Phosphatidylinositol 4-phosphate (PI4P) is the organelle-specific
      phosphoinositide enriched at sites of HCV replication. Whether retromer, a PI4P
      related host transport machinery, unloads its cargo at HCV replication sites
      remains inconclusive. We sought to characterize the role of retromer in HCV
      replication. Here, we demonstrated the interaction between retromer subunit Vps35
      and HCV NS5A protein by immunoprecipitation and GST pulldown. Vps35 colocalized
      with NS5A and PI4P in both OR6 replicon and JFH1 infected Huh 7.5.1 cells. HCV
      replication was inhibited upon silencing retromer subunits. CIMPR, a typical
      retromer cargo, participated in HCV replication. Our data suggest that retromer
      component Vps35 is recruited by NS5A to viral replication sites where PI4P
      unloads CIMPR. These findings demonstrate a dependence role of retromer in HCV
      replication and identify retromer as a potential therapeutic target against HCV. 

PMID- 26298291
TI  - HIF-1-driven skeletal muscle adaptations to chronic hypoxia: molecular insights
      into muscle physiology.
AB  - Skeletal muscle is a metabolically active tissue and the major body protein
      reservoir. Drop in ambient oxygen pressure likely results in a decrease in muscle
      cells oxygenation, reactive oxygen species (ROS) overproduction and stabilization
      of the oxygen-sensitive hypoxia-inducible factor (HIF)-1alpha. However, skeletal
      muscle seems to be quite resistant to hypoxia compared to other organs, probably
      because it is accustomed to hypoxic episodes during physical exercise. Few
      studies have observed HIF-1alpha accumulation in skeletal muscle during ambient
      hypoxia probably because of its transient stabilization. Nevertheless, skeletal
      muscle presents adaptations to hypoxia that fit with HIF-1 activation, although
      the exact contribution of HIF-2, I kappa B kinase and activating transcription
      factors, all potentially activated by hypoxia, needs to be determined. Metabolic
      alterations result in the inhibition of fatty acid oxidation, while activation of
      anaerobic glycolysis is less evident. Hypoxia causes mitochondrial remodeling and
      enhanced mitophagy that ultimately lead to a decrease in ROS production, and this
      acclimatization in turn contributes to HIF-1alpha destabilization. Likewise,
      hypoxia has structural consequences with muscle fiber atrophy due to mTOR
      dependent inhibition of protein synthesis and transient activation of
      proteolysis. The decrease in muscle fiber area improves oxygen diffusion into
      muscle cells, while inhibition of protein synthesis, an ATP-consuming process,
      and reduction in muscle mass decreases energy demand. Amino acids released from
      muscle cells may also have protective and metabolic effects. Collectively, these
      results demonstrate that skeletal muscle copes with the energetic challenge
      imposed by O2 rarefaction via metabolic optimization.

PMID- 26298295
TI  - Multiple primary melanomas among 16,570 patients with melanoma diagnosed at
      Kaiser Permanente Northern California, 1996 to 2011.
AB  - BACKGROUND: Published rates of cutaneous multiple primary melanoma (MPM) vary
      widely. OBJECTIVE: We examined incidence of and risk factors associated with MPMs
      among Kaiser Permanente Northern California members. METHODS: We estimated MPM
      incidence among 16,570 patients with melanoma from 1996 through 2011. We compared
      characteristics between patients with MPMs and single primary melanomas and
      estimated crude and adjusted hazard ratios of MPMs using Cox models. RESULTS: In
      all, 15,448 patients had a single melanoma and 1122 had MPMs. Patients with MPMs
      were older and more often male, non-Hispanic white, and partnered. Subsequent
      primary melanomas were diagnosed after a mean of 3.83 (SD 3.61, median 2.82)
      years and were more likely in situ and thinner than initial tumors. The risk of a
      subsequent melanoma decreased from 2% in the first year after diagnosis to a
      stable approximately 1% rate through 15 years of follow-up. LIMITATIONS: We
      lacked data on some known melanoma risk factors and had small numbers of non
      white patients and certain tumor subtypes. CONCLUSIONS: The risk of MPMs,
      although highest in the first year after diagnosis, remains stable thereafter.
      Those at highest risk of MPMs are older, male, white, and partnered. Clinicians
      should be aware of the rate of MPMs and recognize high-risk subgroups.

PMID- 26298294
TI  - Automatically visualise and analyse data on pathways using PathVisioRPC from any
      programming environment.
AB  - BACKGROUND: Biological pathways are descriptive diagrams of biological processes
      widely used for functional analysis of differentially expressed genes or
      proteins. Primary data analysis, such as quality control, normalisation, and
      statistical analysis, is often performed in scripting languages like R, Perl, and
      Python. Subsequent pathway analysis is usually performed using dedicated external
      applications. Workflows involving manual use of multiple environments are time
      consuming and error prone. Therefore, tools are needed that enable pathway
      analysis directly within the same scripting languages used for primary data
      analyses. Existing tools have limited capability in terms of available pathway
      content, pathway editing and visualisation options, and export file formats.
      Consequently, making the full-fledged pathway analysis tool PathVisio available
      from various scripting languages will benefit researchers. RESULTS: We developed
      PathVisioRPC, an XMLRPC interface for the pathway analysis software PathVisio.
      PathVisioRPC enables creating and editing biological pathways, visualising data
      on pathways, performing pathway statistics, and exporting results in several
      image formats in multiple programming environments. We demonstrate PathVisioRPC
      functionalities using examples in Python. Subsequently, we analyse a publicly
      available NCBI GEO gene expression dataset studying tumour bearing mice treated
      with cyclophosphamide in R. The R scripts demonstrate how calls to existing R
      packages for data processing and calls to PathVisioRPC can directly work
      together. To further support R users, we have created RPathVisio simplifying the
      use of PathVisioRPC in this environment. We have also created a pathway module
      for the microarray data analysis portal ArrayAnalysis.org that calls the
      PathVisioRPC interface to perform pathway analysis. This module allows users to
      use PathVisio functionality online without having to download and install the
      software and exemplifies how the PathVisioRPC interface can be used by data
      analysis pipelines for functional analysis of processed genomics data.
      CONCLUSIONS: PathVisioRPC enables data visualisation and pathway analysis
      directly from within various analytical environments used for preliminary
      analyses. It supports the use of existing pathways from WikiPathways or pathways
      created using the RPC itself. It also enables automation of tasks performed using
      PathVisio, making it useful to PathVisio users performing repeated visualisation
      and analysis tasks. PathVisioRPC is freely available for academic and commercial
      use at http://projects.bigcat.unimaas.nl/pathvisiorpc.

PMID- 26298296
TI  - [Seroconversion in response to a reinforced primary hepatitis B vaccination in
      children with cancer].
AB  - INTRODUCTION: Immune response against vaccine antigens may be impaired in
      children with cancer. The aim of this study was to evaluate the seroconversion
      response against hepatitis B vaccination (HBV) at the time of chemotherapy onset
      and/or remission in children with cancer. PATIENTS AND METHOD: Prospective, two
      centre, controlled, non-randomised study conducted on children recently diagnosed
      with cancer, paired with healthy subjects. Cases received HBV at time 0, 1 and 6
      months with DNA recombinant HBV at a dose of 20 and 40 MUg if < or > than 10
      years of age, respectively, at the time of diagnosis for solids tumours and after
      the remission in case of haematological tumours. Controls received the same
      schedule, but at of 10 and 20 MUg doses, respectively. HBs antibodies were
      measured in serum samples obtained at 2, 8 and 12 months post-vaccination.
      Protective titres were defined as > 10 mIU/ml at 8th month of follow up. RESULTS:
      A total of 78 children with cancer and 25 healthy controls were analysed at month
      8th of follow up. Seroconversion rates in the cancer group reached 26.9%, with no
      differences by age, gender or type of tumour (P = .13, .29, and .44,
      respectively). Control group seroconversion was 100% at the 8th month, with P <
      .0001 compared with the cancer group. At month 12 of follow up, just 31.9% of
      children with cancer achieved anti-HBs antibodies > 10 mIU/ml. CONCLUSIONS:
      Vaccination against hepatitis B with three doses of DNA recombinant vaccine at an
      increased concentration, administrated at the time of onset of chemotherapy
      and/or remission provided an insufficient immune response in a majority of
      children with cancer. More immunogenic vaccines should be evaluated in this
      special population, such as a third generation, with more immunogenic adjuvants,
      enhanced schedules at 0, 1, 2, 6 month, evaluation of antibody titres at month 8
      and 12h to evaluate the need for further booster doses.

PMID- 26298297
TI  - [Hospital Admissions due to cyanosis episodes in newborns with gestational age of
      34 weeks or more].
AB  - OBJECTIVES: A retrospective study was performed between January 2007 and December
      2012 to assess the admission rates of newborns due to episodes of cyanosis
      PATIENTS AND METHOD: Retrospective study that included all the newborns
      hospitalized with episodes of cyanosis between January 2007 and December 2012. In
      them were employed two study protocols that considered first and second line
      tests, the latter in view of recurrence of events. The first line protocol
      considered general biochemical tests, chest x-ray and echocardiography in
      selected cases, while the second line protocol included electroencephalogram,
      electrocardiogram, nuclear magnetic resonance of the brain, expanded metabolic
      screening, pyruvic acid, lactic acid, and in case of seizures, cytochemical, and
      culture of cerebrospinal fluid (CSF) and PCR (polymerase chain reaction) for
      herpes. RESULTS: A total of 98 (2.8%) out of 3,454 newborns were admitted due to
      episodes of cyanosis. Gestational age: 37.8+1.4 weeks, birth weight: 3,145+477 g.
      Maternal age: 32+4.8 years. Disease was present in 19.4% of mothers; gestational
      diabetes (8.1%), pregnancy induced hypertension (5.1%), intrahepatic cholestasis
      (3.1%), and intrauterine growth retardation (3.1%). Gender: 48.8% male, 51.2%
      female (NS). Birth: caesarean section, 68.4%, and vaginal delivery, 31.6%. Age on
      admission 1.9+1.4 days. Hospital stay: 4.2+4.2 days. First line tests were
      performed in 100% of patients with 39.8% fulfilling the criteria for second line
      study. A condition was detected in 21.4%, with convulsive syndrome was the most
      frequent (33%). Newborns with an identified condition had 3.8+2.7 episodes versus
      1.5+2,4 in those without diagnosis (NS). A home oxygen monitor was given to
      15.4%. There were no re-admissions. CONCLUSIONS: Most newborns admitted due to
      cyanosis are discharged with a condition of unknown origin. In this study,
      convulsive syndrome was the most frequent cause.

PMID- 26298298
TI  - [Aetiology of childhood alopecia].
AB  - INTRODUCTION: Childhood alopecia is a relative rare event in general paediatric
      dermatology practice. Hair loss in children may have multiple causes, and there
      are different types of alopecia according to age groups. The aim of the study was
      to describe the clinical and epidemiological profile of alopecia in children from
      two Chilean paediatric hospitals. PATIENTS AND METHOD: Descriptive analysis of
      clinical records of patients from the Dermatology Department of Roberto del Rio
      and Luis Calvo Mackenna Hospitals between January 2007 and June 2010. Patients
      with clinical diagnosis of alopecia were included. RESULTS: A total of 345
      clinical records were analysed, with 179 males (51.9%). The median age was 72
      months. Overall, the most common diagnoses were: alopecia areata (AA), (36.8%),
      tinea capitis (TC), (21%), nevus sebaceous (13.2%), and tellogen effluvium
      (8.7%). According to age groups, in newborns, the most common causes were aplasia
      cutis and nevus sebaceous. In toddlers, pre-school and school children, the
      principal causes were nevus sebaceous, AA and TC. Trichotillomania was also
      significant in school children. In adolescents, nevus sebaceous, AA and tellogen
      effluvium were the most frequent diagnoses. AA was statistically associated with
      autoimmune disease, thyroid disease, nail disorder, psychiatric disease, and
      Down's syndrome. The most common aetiological agent in TC was M. canis (86.6%).
      Trichotillomania was also statistically associated to psychiatric disorders.
      CONCLUSIONS: In this study, the main causes of alopecia in children were acquired
      and non-scarring alopecia. In our results, the type of alopecia varies according
      to age group. Some types of childhood alopecia showed a close correlation to
      psychiatric disorders.

PMID- 26298299
TI  - [Severe rhabdomyolysis secondary to severe hypernatraemic dehydration].
AB  - INTRODUCTION: Rhabdomyolysis is a rare paediatric condition. The case is
      presented of a patient in whom this developed secondary to severe hypernatraemic
      dehydration following acute diarrhoea. CASE REPORT: Infant 11 months of age who
      presented with vomiting, fever, diarrhoea and anuria for 15 hours. Parents
      reported adequate preparation of artificial formula and oral rehydration
      solution. He was admitted with malaise, severe dehydration signs and symptoms,
      cyanosis, and low reactivity. The laboratory tests highlighted severe metabolic
      acidosis, hypernatraemia and pre-renal kidney failure (Sodium [Na] plasma 181
      mEq/L, urine density> 1030). He was managed in Intensive Care Unit with gradual
      clinical and renal function improvement. On the third day, slight axial hypotonia
      and elevated cell lysis enzymes (creatine phosphokinase 75,076 IU/L) were
      observed, interpreted as rhabdomyolysis. He was treated with intravenous
      rehydration up to 1.5 times the basal requirements, and he showed a good clinical
      and biochemical response, being discharged 12 days after admission without motor
      sequelae. CONCLUSIONS: Severe hypernatraemia is described as a rare cause of
      rhabdomyolysis and renal failure. In critically ill patients, it is important to
      have a high index of suspicion for rhabdomyolysis and performing serial
      determinations of creatine phosphokinase for early detection and treatment.

PMID- 26298300
TI  - [Secular variation of births, weight and length at birth: Local perspective].
AB  - OBJECTIVE: To analyse the outcomes of births and anthropometric measurements at
      birth of children born between 1974 and 2011 at Limache Hospital (Valparaiso,
      Chile). PATIENTS AND METHOD: Times series were constructed of births, weight and
      length at birth, and low weight and length at birth. The trend was modelled with
      linear and logistical regressions using splines to represent breaks in the trend
      by decade. RESULTS: The series includes 17,574 births. There was an increase in
      births per year in the 1970s (30/year) and declines in them to 17 and 22
      births/year in the 1980s and 1990s, respectively (P<.001), with no significant
      trend thereafter. Newborns from 2000 to 2011 weighed 266 grams more than those in
      the 1970s (P<.001), and have now reached a mean weight of 3,530 g. Low
      birthweight fell from 8% in the 1970s to 1.1% after 2000. Birth length increased
      by 1cm in the 37 years studied, with a reduction of low birth length from 7.6% to
      2.1% during the period. CONCLUSION: Live births in the Limache Hospital declined,
      and anthropometric measurements at birth improved in the years analysed. This
      information is useful in developing interventions, taking into account the
      possible selection biases that could distort these estimates and their
      interpretation.

PMID- 26298301
TI  - [Self-concept level in children with burns sequelae: A comparative study].
AB  - INTRODUCTION: Self-concept is the set of ideas and attitudes that a person has
      about him/herself. OBJECTIVE: To evaluate whether there are differences in the
      level of self-concept in children 8-12 years old with and without burns sequelae.
      To identify predictive variables of self-concept in children with sequelae.
      PATIENTS AND METHOD: A comparative cross-sectional study of self-concept in 109
      children with burns sequelae, from 8 to 12 years old, with 109 children without
      burns sequelae, and of the same age and socioeconomic status. The Piers-Harris
      self-concept scale is used, which provides a general measurement of self-concept
      and behavioural, intellectual and school status, appearance, and physical
      attributes, anxiety, popularity, happiness and satisfaction dimensions. RESULTS:
      There were no significant differences in the level of general self-concept or
      their dimensions (P>.05). In the group with burns sequelae, the protective factor
      was the variable number of sequels was associated with the dimensions of anxiety,
      popularity, happiness-satisfaction and general self-concept. The location
      variable emerged as a risk factor for the behavioural dimension. DISCUSSION: The
      absence of differences in self-concept between children with burns sequelae and
      children without them is similar to that reported in the literature. The finding
      in the risk and protective factors encourages to further research, and perhaps
      incorporating pre-morbidity and family background.

PMID- 26298302
TI  - Enzymatic Assays Coupled with Mass Spectrometry with or without Embedded Liquid
      Chromatography.
AB  - This article reviews monitoring strategies for enzymatic assays coupled with mass
      spectrometric detection. This coupling has already been shown to be helpful in
      providing versatile and detailed knowledge about enzyme kinetics. Various
      available publications address two general approaches. 1) The continuous-flow
      setup allows real-time determination of substrate degradation. Simultaneously,
      resulting product or potential intermediates can be detected. 2) The online
      coupled continuous-flow mixing assay allows the direct coupling of an enzymatic
      assay to chromatographic separation of complex mixtures. The latest efforts in
      improving the methodology have been made with regard to miniaturization. This is
      especially advantageous with regard to reducing costly consumption of chemicals.
      Finally, these developments are applicable for diverse bioanalytical purposes in
      the realms of pharmaceutical, biotechnological, food, and environmental research.

PMID- 26298303
TI  - Adult-plant resistance to Septoria tritici blotch in hexaploid spring wheat.
AB  - KEY MESSAGE: New QTL for Septoria tritici blotch detected in hexapoid spring
      wheat under field conditions across diverse environments. Septoria tritici blotch
      caused by the ascomycete fungus Zymoseptoria tritici presents a serious and
      consistent challenge to global wheat production. In particular the augmented use
      of soil management practices that leave large amounts of wheat stubble on the
      soil surface and global warming increases the chance of Septoria tritici blotch
      epidemics to emerge more frequently including in developing countries. Two
      recombinant inbred line populations developed from a cross between the
      susceptible Moroccan spring bread wheat variety 'NASMA' and the CIMMYT resistant
      lines, 'IAS20*5/H567.71' and 'RPB709.71/COC' were used to study the genetics and
      map adult-plant resistance to Septoria tritici blotch under field conditions in
      different environments. Resistance to Septoria tritici blotch in both populations
      was quantitative and overall, five across environment consistent resistance loci
      on chromosomes 1BS, 3AL, 5AL and 7AS were detected in the two populations. The
      QTL on chromosome 1BS and 7AS are likely to be allelic with the known Septoria
      tritici blotch genes Stb3 and Stb11. All identified QTL were additive and
      explained between 4 and 27 % of the phenotypic variation. Epistatic interaction
      was not observed. Low cost KASP assays were developed as flanking markers for all
      five QTL that will facilitate molecular breeding. Our study represents the first
      mapping effort under field conditions utilizing two spring bread wheat resistant
      sources evaluated over multiple environments.

PMID- 26298304
TI  - Comparison of Successful Myocardial Reperfusion and Adverse Events in Patients
      With ST-Elevation Myocardial Infarction Who Underwent Rescue Percutaneous
      Coronary Intervention After Failed Fibrinolytic Therapy With Versus Without
      Manual Coronary Thrombus Aspiration.
AB  - It has been unclear the impact of manual thrombus aspiration (TA) on procedural
      outcomes in patients with ST-elevation myocardial infarction (STEMI) who
      underwent rescue percutaneous coronary intervention (PCI) after failed
      fibrinolytic therapy in comparison with primary PCI. Our aim was to test the
      hypothesis that manual TA may improve myocardial reperfusion and clinical
      outcomes in patients with STEMI who underwent rescue PCI after failed
      fibrinolytic therapy. From March 2011 to March 2014, 70 patients with STEMI after
      unsuccessful fibrinolysis were randomized to either rescue PCI with TA (TA group)
      or without TA (NTA group). Primary end points were rate of myocardial blush grade
      >=2 and ST-segment resolution >=70%. The secondary end point included 30 days
      follow-up for major adverse cardiac events (MACEs). Baseline clinical and
      angiographic characteristics were similar in the 2 groups. The TA and NTA groups
      were compared as follows: myocardial blush grade >=2, 71% versus 46% (p <0.05);
      complete ST-segment resolution 71% versus 46% (p <0.05); no reflow 20% versus 49%
      (p <0.05); procedure time (min) 65.0 +/- 38.6 versus 90.1 +/- 28.8 (p <0.05);
      contrast amount (ml) 99.0 +/- 45.2 versus 121.2 +/- 33.4 (p <0.05); and direct
      stenting 60% versus 37% (p <0.05). There was a significant reduction of MACE in
      the TA group, 20% versus 37% (p <0.05). In conclusion, rescue PCI with manual TA
      leads to better myocardial reperfusion and significant reduction of MACE. 

PMID- 26298305
TI  - Reduced Irregularity of Ventricular Response During Atrial Fibrillation and Long
      term Outcome in Patients With Heart Failure.
AB  - Reduced heart rate variability (HRV) is associated with poor outcome in patients
      with heart failure (HF). However, the data on predictive value of RR variability
      during atrial fibrillation (AF) are limited. Therefore, the aim of this study was
      to evaluate the association between ventricular response characteristics and long
      term clinical outcome in the population of ambulatory patients with mild-to
      moderate HF and AF at baseline. The study included 155 patients (mean age 69 +/-
      10 years) with AF at 20-minute Holter electrocardiographic (ECG) recordings at
      enrollment. HRV analysis included SDNN, rMSSD, and pNN50, whereas irregularity
      indexes included 2 nonlinear parameters: approximate entropy (ApEn) and Shannon
      entropy. After median 41 months of follow-up, 54 patients died, including 21 HF
      related and 16 sudden deaths. Patients with ApEn <=1.68 (lower tertile) had 40%
      mortality versus 12% in others (p <0.001) at 2 years of follow-up. Only nonlinear
      HRV parameters (irregularity but not variability indexes) identified patients at
      higher risk during follow-up. Decreased ApEn <=1.68 was an independent predictor
      of total mortality (hazard ratio [HR] 2.81, 95% confidence interval [CI] 1.61 to
      4.89, p <0.001), sudden cardiac death (HR 3.83, 95% CI 1.31 to 11.25, p = 0.014),
      and HF death (HR 3.45, 95% CI 1.42 to 8.38, p = 0.006) in a multivariate Cox
      analysis. In conclusion, in a post hoc analysis of Muerte Subita en
      Insufficiencia Cardiaca study AF cohort, reduced irregularity of RR intervals
      during AF, likely caused by autonomic dysfunction, was an independent predictor
      of all-cause mortality and sudden death and HF progression in patients with mild
      to-moderate HF, whereas traditional HRV indexes did not predict outcome. 

PMID- 26298306
TI  - The impact of drugs, infants, single mothers, and relatives on reunification: A
      Decision-Making Ecology approach.
AB  - Using a Decision-Making Ecology (DME) approach and proportional hazards models,
      the study isolated four case factor profiles that interacted strongly with race
      and resulted in disparate reunification outcomes for African American children
      compared with Anglos. The four interrelated factors were drug involvement, a solo
      infant case, single mothers, and relative placements. A cohort of 21,763 children
      from the Texas Department of Family and Protective Services who were placed for
      the first time in care, who were under 13 and either Anglo or African American
      were followed for 20 months or more post entry into care. Starting with an
      initial model consisting of main effects only and consistent with other studies,
      African American children had a 12% lower hazard rate of reunification compared
      to Anglo children. However, when a set of case profiles involving combinations of
      single parents, single infants, drug involvements and kinship placements were
      crossed with race, the magnitude of the effect of race on hazard rates fanned out
      from no difference to as much as 68% that of Anglo children. The results show
      that racial disparities in outcomes resulting from complex, contextual decision
      making cannot be modeled well with simple main effects models. 

PMID- 26298307
TI  - Emotional triggering of cardiac dysfunction: the present and future.
AB  - Mental stress and emotional arousal can act as triggers of acute myocardial
      infarction and other adverse cardiovascular outcomes. Experimental research
      examining mechanisms of the adverse interplay between mind and heart has led to
      the discovery of mental stress-induced cardiac dysfunction or myocardial ischemia
      (MSIMI). Evidence about the prevalence, clinical significance, and mechanistic
      bases of MSIMI outlines a wide range of central and peripheral bio-pathologic
      processes that are associated with emotions and behaviors. MSIMI is recognized as
      an integrated and intermediate biomarker underpinning the negative mind-heart
      interplay. Particularly, MSIMI research paves the way toward investigations
      aiming more specifically at recognizing the susceptibilities of individuals who
      are prone to respond adversely to the psycho-social-environmental stress. This
      article reviews recent literature on MSIMI research following the comprehensive
      review of Strike and Steptoe Eur Heart J 24:690-703, 2003. Further, this article
      outlines the main steps in the identification of the specific bio-pathologic
      manifestations of the cardiovascular system to emotional stress. Finally, a
      speculative description is provided of future directions in better searching for
      areas that may be critical targets in resolving adverse mind-heart interplays. 

PMID- 26298308
TI  - Cardiac resynchronization therapy update: evolving indications, expanding
      benefit?
AB  - Cardiac resynchronisation therapy (CRT) is an effective intervention for
      appropriately selected patients with heart failure, but exactly how it works is
      uncertain. Recent data suggest that much, or perhaps most, of the benefits of CRT
      are not delivered by re-coordinating left ventricular dyssynchrony. Atrio
      ventricular resynchronization, reduction in mitral regurgitation and prevention
      of bradycardia are other potential mechanisms of benefit that will vary from one
      patient to the next and over time. Because there is no single therapeutic target,
      it is unlikely that any single measure will accurately predict benefit. The only
      clinical characteristic that appears to be a useful predictor of the benefits of
      CRT is a QRS duration of >140 ms. Many new approaches are being developed to try
      to improve the effectiveness of and extend the indications for CRT. These include
      smart pacing algorithms, better pacing-site targeting, new sensors, multipoint
      pacing, remote device monitoring and leadless endocardial pacing. Whether CRT is
      effective in patients with atrial fibrillation or whether adding a defibrillator
      function to CRT improves prognosis awaits further evidence. 

PMID- 26298310
TI  - Making the Case to Study the Volume-Outcome Relationship in Hematologic Cancers.
AB  - The positive relationship between the volume of health services (hospital and
      physician) and health-related outcomes is established in the complex surgical
      treatment of cancers and certain nononcologic medical conditions. However, this
      topic has not been systematically explored in the medical management of cancers.
      We summarize the limited current state of knowledge about the volume-outcome
      relationship in the management of hematologic cancers and provide reasons why
      further research on this subject is necessary. We highlight the relatively low
      annual volume of hematologic cancers in the United States, the increasing
      complexity of making a diagnosis due to constant change in classification and
      prognostication, the rapid availability of novel agents with unique mechanisms of
      action and toxicities, and the proliferation of treatment guidelines distinct to
      each disease subtype. We also discuss the potential implications pertaining to
      medical practice and trainee education, including effects on quality of care,
      access and referral patterns, and subspecialty training. 

PMID- 26298309
TI  - Disrupted glutamate-glutamine cycle in acute encephalopathy with biphasic
      seizures and late reduced diffusion.
AB  - INTRODUCTION: Acute encephalopathy with biphasic seizures and late reduced
      diffusion (AESD) is the most common subtype of infectious pediatric
      encephalopathy in Japan. It is sometimes difficult to make an early diagnosis of
      AESD; excitotoxicity is postulated to be the pathogenesis based on elevated
      glutamine (Gln) and glutamate (Glu) complex (Glx = Glu + Gln) observed on MR
      spectroscopy. It is uncertain whether Gln or Glu contributes to the elevated Glx,
      or whether MR spectroscopy is useful for an early diagnosis. METHODS: Five
      Japanese patients with AESD (three boys and two girls, 1 year of age) were
      enrolled in this study. MR spectroscopy was acquired from the frontal white
      matter (repetition time (TR) of 5000 ms, echo time (TE) of 30 ms) with a 1.5- or
      3.0-T scanner. MR spectroscopy was performed four times for two patients, three
      times for one patient, and two times for two patients. Quantification of Glu and
      Gln was performed using LCModel. RESULTS: Glu was elevated in three of four
      studies on days 1-4 and became normal or low afterward. Gln was normal in three
      studies on days 1-2, elevated in all seven studies on days 4-12, and became
      normal or low afterward. CONCLUSION: These findings suggest that MR spectroscopy
      may be useful for an early diagnosis. Acute Glu elevation changes to subacute Gln
      elevation, suggesting that a disrupted Glu-Gln cycle may play an important role.

PMID- 26298311
TI  - Vaccines for preventing infection with Pseudomonas aeruginosa in cystic fibrosis.
AB  - BACKGROUND: Chronic pulmonary infection in cystic fibrosis results in progressive
      lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs,
      it is almost impossible to eradicate. Vaccines, aimed at reducing infection with
      Pseudomonas aeruginosa, have been developed. This is an update of a previously
      published review. OBJECTIVES: To assess the effectiveness of vaccination against
      Pseudomonas aeruginosa in cystic fibrosis. SEARCH METHODS: We searched the
      Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register using the
      terms vaccines AND pseudomonas (last search 30 March 2015). We previously
      searched PubMed using the terms vaccin* AND cystic fibrosis (last search 30 May
      2013). SELECTION CRITERIA: Randomised trials (published or unpublished) comparing
      Pseudomonas aeruginosa vaccines (oral, parenteral or intranasal) with control
      vaccines or no intervention in cystic fibrosis. DATA COLLECTION AND ANALYSIS: The
      authors independently selected trials, assessed them and extracted data. MAIN
      RESULTS: Six trials were identified. Two trials were excluded since they were not
      randomised and one old, small trial because it was not possible to assess whether
      is was randomised. The three included trials comprised 483, 476 and 37 patients,
      respectively. No data have been published from one of the large trials, but the
      company stated in a press release that the trial failed to confirm the results
      from an earlier study and that further clinical development was suspended. In the
      other large trial, relative risk for chronic infection was 0.91 (95% confidence
      interval 0.55 to 1.49), and in the small trial, the risk was also close to one.
      In the large trial, one patient was reported to have died in the observation
      period. In that trial, 227 adverse events (4 severe) were registered in the
      vaccine group and 91 (1 severe) in the control group. In this large trial of a
      vaccine developed against flagella antigens, antibody titres against the epitopes
      contained in the vaccine were higher in the vaccine group compared to the placebo
      group (P < 0.0001). AUTHORS' CONCLUSIONS: Vaccines against Pseudomonas aeruginosa
      cannot be recommended.

PMID- 26298312
TI  - Effects of an antioxidant beverage on biomarkers of oxidative stress in
      Alzheimer's patients.
AB  - PURPOSE: The purpose of the study was to test whether daily consumption of a
      beverage with high antioxidant power, combining extracts of green tea and apple
      over a period of 8 months, would affect blood and urinary concentrations of
      biomarkers of oxidative stress in Alzheimer's patients. METHODS: The study
      included 100 subjects, 48 of them were Alzheimer's patients, aged 76.5 +/- 3.5
      years, and 52 were control subjects, aged 79 +/- 4 years, without dementia. Three
      blood and urine samples were taken from each participant, the first (T i) before
      starting the antioxidant or placebo beverage intake, the second (T m) 4 months
      after the antioxidant or placebo beverage intake and the third (T f) 8 months
      after the antioxidant or placebo beverage intake, and concentrations of
      biomarkers of oxidative stress were measured on serum, lysed erythrocytes or
      urine by UV-Vis spectrophotometry or by competitive in vitro enzyme-linked
      immunosorbent assay, according to the parameter analyzed. RESULTS: The
      administration of the antioxidant beverage to the Alzheimer's patients prevented
      the decrease in total antioxidant status in the moderate phase of the disease (T
      i = 1.40 +/- 0.10 mmol/L vs T f = 1.20 +/- 0.08 mmol/L), increased values of
      glutathione peroxidase and superoxide dismutase in initial (165 and 24 %
      respectively) and moderate phase (75 and 85 % respectively), and prevented the
      increase in protein carbonyls in moderate phase (T i = 0.17 +/- 0.07 nmol/mg
      protein vs T f = 0.21 +/- 0.06 nmol/mg protein), with a significant decrease in
      protein carbonyls since the fourth month of the intake in initial phase (T m =
      0.21 +/- 0.06 nmol/mg protein vs T f = 0.11 +/- 0.05 nmol/mg protein).
      CONCLUSION: Our results suggest that antioxidant beverage could be used as a
      natural complementary therapy for alleviate or decrease the oxidative stress
      effects in the stages of Alzheimer's disease.

PMID- 26298313
TI  - A reduced-dimensional model for near-wall transport in cardiovascular flows.
AB  - Near-wall mass transport plays an important role in many cardiovascular
      processes, including the initiation of atherosclerosis, endothelial cell
      vasoregulation, and thrombogenesis. These problems are characterized by large
      Peclet and Schmidt numbers as well as a wide range of spatial and temporal
      scales, all of which impose computational difficulties. In this work, we develop
      an analytical relationship between the flow field and near-wall mass transport
      for high-Schmidt-number flows. This allows for the development of a wall-shear
      stress-driven transport equation that lies on a codimension-one vessel-wall
      surface, significantly reducing computational cost in solving the transport
      problem. Separate versions of this equation are developed for the reaction-rate
      limited and transport-limited cases, and numerical results in an idealized
      abdominal aortic aneurysm are compared to those obtained by solving the full
      transport equations over the entire domain. The reaction-rate-limited model
      matches the expected results well. The transport-limited model is accurate in the
      developed flow regions, but overpredicts wall flux at entry regions and
      reattachment points in the flow.

PMID- 26298314
TI  - Thymidine Phosphorylase in Cancer; Enemy or Friend?
AB  - Thymidine phosphorylase (TP) is a nucleoside metabolism enzyme that plays an
      important role in the pyrimidine pathway.TP catalyzes the conversion of thymidine
      to thymine and 2-deoxy-alpha-D-ribose-1-phosphate (dRib-1-P). Although this
      reaction is reversible, the main metabolic function of TP is catabolic. TP is
      identical to the angiogenic factor platelet-derived endothelial-cell growth
      factor (PD-ECGF). TP is overexpressed in several human cancers in response to
      cellular stressful conditions like hypoxia, acidosis, chemotherapy and
      radiotherapy. TP has been shown to promote tumor angiogenesis, invasion,
      metastasis, evasion of the immune-response and resistance to apoptosis. Some of
      the biological effects of TP are dependent on its enzymatic activity, while
      others are mediated through cytokines like interleukin 10 (IL-10), basic
      fibroblast growth factor (bFGF) and tumour necrosis factor alpha (TNFalpha).
      Interestingly, TP also plays a role in cancer treatment through its role in the
      conversion of the oral fluoropyrimidine capecitabine into its active form 5-FU.
      TP is a predictive marker for fluoropyrimidine response. Given its various
      biological functions in cancer progression, TP is a promising target in cancer
      treatment. Further translational research is required in this area. 

PMID- 26298315
TI  - Independent association between brachial-ankle pulse wave velocity and global
      longitudinal strain of left ventricle.
AB  - Data regarding the influence of arterial stiffness on left ventricular (LV) long
      axis function has been scarce. This study was performed to investigate the
      association between brachial-ankle pulse wave velocity (baPWV) and LV global
      longitudinal strain (GLS). A total of 248 subjects (mean age 59.2 +/- 12.3 years;
      50% were men) without structural heart problems were retrospectively evaluated.
      LV GLS was measured by 2-dimensional speckle-tracking echocardiography. baPWV
      measurements were made on the same day of echocardiography. The incidences of
      hypertension, diabetes mellitus, and dyslipidemia were 51.2, 19.4, and 22.2%,
      respectively. The mean value of baPWV was 1557 +/- 285 cm/s. In simple linear
      regression analysis, baPWV had a significant positive association with LV GLS
      (beta = 0.215, P = 0.001). In multiple linear regression analysis, baPWV was
      independently associated with LV GLS even after controlling for potential
      confounders, including age, gender, body mass index, systolic blood pressure,
      heart rate, HbA1c, total cholesterol, estimated glomerular filtration rate, left
      ventricular mass index, E/A, septal e' velocity and pulmonary artery systolic
      pressure (beta = 0.211, P = 0.028). The results of this study suggest that baPWV
      may be independently associated with LV GLS, supporting the evidence of a close
      interaction between arterial stiffness and LV function. Increased arterial
      stiffness may result in impaired LV longitudinal function.

PMID- 26298316
TI  - Characterizing and evaluating the expression of the type IIb sodium-dependent
      phosphate cotransporter (slc34a2) gene and its potential influence on phosphorus
      utilization efficiency in yellow catfish (Pelteobagrus fulvidraco).
AB  - A sodium-dependent phosphate cotransporter gene, NaPi-IIb (slc34a2), was isolated
      from yellow catfish (Pelteobagrus fulvidraco) intestine through homology cloning
      and the rapid amplification of cDNA ends. The full-length cDNA of slc34a2
      consisted of 2326 bp with an open reading frame encoding 621 amino acids, a 160
      bp 5' untranslated region, and a 300-bp 3' untranslated region. The deduced amino
      acid sequence showed 79.0 and 70.9% sequence identity to Astyanax mexicanus and
      Pundamilia nyererei, respectively. The membrane-spanning domains based on the
      hydrophilic and hydrophobic properties of the deduced amino acids were predicted,
      and results showed that the putative protein had eight transmembrane domains,
      with the intracellular NH2 and COOH termini. Two functional regions including
      first intracellular loop and third extracellular loop as well as the six N
      glycosylation sites in second extracellular loop were found. The slc34a2 mRNA in
      the tested tissues was examined through semiquantitative reverse transcription
      polymerase chain reaction and quantitative real-time PCR, with the highest level
      found in the anterior intestine, followed by the posterior and middle intestines.
      The slc34a2 mRNA expression in the whole intestine under different dietary
      phosphorus (P) treatments was detected using qPCR. The results showed that the
      slc34a2 expression levels in the low-P groups (0.33 and 0.56%) were significantly
      higher (p < 0.05) than levels in the sufficient-P (0.81%) and high-P (1.15, 1.31,
      and 1.57%) groups. High expression of slc34a2 mRNA in low-P groups stimulated P
      utilization efficiency, indicating the close relationship between genotype and
      phenotype in yellow catfish. In contrast with conventional strategies (formula
      and feeding strategies), this study provided another possible approach by using
      molecular techniques to increase the P utilization in yellow catfish.

PMID- 26298317
TI  - Cytokine profiles in multifocal motor neuropathy and progressive muscular
      atrophy.
AB  - Multifocal motor neuropathy (MMN) and progressive muscular atrophy (PMA) are
      associated with IgM monoclonal gammopathy or the presence IgM anti-GM1
      antibodies. To further investigate the pathophysiology of MMN and PMA we
      determined concentrations of 16 mainly B-cell associated inflammatory markers in
      serum from 25 patients with MMN, 55 patients with PMA, 25 patients with
      amyotrophic lateral sclerosis (ALS) and 50 healthy controls. Median serum
      concentrations of the 16 tested cytokines and chemokines were not significantly
      increased in patients with MMN or patients with PMA, irrespective of the presence
      of IgM monoclonal gammopathy or high IgM anti-GM1 antibodies. These results argue
      against a systemic B-cell mediated immune response underlying the pathogenesis of
      MMN and PMA. 

PMID- 26298319
TI  - MMP-2 -1575G/A polymorphism modifies the onset of optic neuritis as a first
      presenting symptom in MS?
AB  - Previous studies show altered activities of matrix metalloproteinase (MMP)-2 and
      MMP-9 in serum and cerebrospinal fluid of multiple sclerosis (MS) and
      neuromyelitis optica (NMO) patients. Optic neuritis (ON) is a common symptom of
      both disorders. Here we investigated the impacts of MMP-2 -1575G/A and MMP-9 
      1562 C/T gene polymorphisms on disease phenotype in 100 MS patients with ON as a
      first symptom and 376 MS patients with other initial symptomatology. The MMP-2 
      1575G/A polymorphism led to a 5-year-earlier age of disease onset in MS patients
      with ON as a first symptom (p=0.009). 

PMID- 26298318
TI  - Anti-inflammatory effects of thymoquinone in activated BV-2 microglial cells.
AB  - Thymoquinone (TQ), the main pharmacological active ingredient within the black
      cumin seed (Nigella sativa) is believed to be responsible for the therapeutic
      effects on chronic inflammatory conditions such as arthritis, asthma and
      neurodegeneration. In this study, we evaluated the potential anti-inflammatory
      role of TQ in lipopolysaccharide (LPS)-stimulated BV-2 murine microglia cells.
      The results obtained indicate that TQ was effective in reducing NO2(-) with an
      IC50 of 5.04MUM, relative to selective iNOS inhibitor LNIL-l-N6-(1
      iminoethyl)lysine (IC50 4.09MUM). TQ mediated reduction in NO2(-) was found to
      parallel the decline of iNOS protein expression as confirmed by
      immunocytochemistry. In addition, we evaluated the anti-inflammatory effects of
      TQ on ninety-six (96) cytokines using a RayBio AAM-CYT-3 and 4 cytokine antibody
      protein array. Data obtained establish a baseline protein expression profile
      characteristic of resting BV-2 cells in the order of osteopontin>MIP-1alpha>MIP
      1g>IGF-1 and MCP-I. In the presence of LPS [1ug/ml], activated BV-2 cells
      produced a sharp rise in specific pro-inflammatory cytokines/chemokine's IL-6, IL
      12p40/70, CCL12 /MCP-5, CCL2/MCP-1, and G-CSF which were attenuated by the
      addition of TQ (10MUM). The TQ mediated attenuation of MCP-5, MCP-1 and IL-6
      protein in supernatants from activated BV-2 cells were corroborated by
      independent ELISA. Moreover, the data obtained from the RT(2) PCR demonstrated a
      similar pattern where the LPS mediated elevation of mRNA for IL-6, CCL12/MCP-5,
      CCL2/MCP-1 were significantly attenuated by TQ (10MUM). Also, in this study,
      consistent data were obtained for both protein antibody array densitometry and
      ELISA assays. In addition, TQ was found to reduce LPS mediated elevation in gene
      expression of Cxcl10 and a number of other cytokines in the panel. These findings
      demonstrate the significant anti-inflammatory properties of TQ in LPS activated
      microglial cells. Therefore, the obtained results might indicate the usefulness
      of TQ in delaying the onset of inflammation-mediated neurodegenerative disorders
      involving activated microglia cells. 

PMID- 26298321
TI  - Activation and function of murine primary microglia in the absence of the prion
      protein.
AB  - The prion protein (PrP(C)) is predominantly expressed in the nervous and immune
      systems and is involved in relevant cell signaling. Microglia participate in
      neuroimmune interactions, and their regulatory mechanisms are critical for both
      health and disease. Despite recent reports with a microglial cell line, little is
      known about the relevance of PrP(C) in brain microglia. We investigated the role
      of PrP(C) in mouse primary microglia, and found no differences between wild type
      and Prnp-null cells in cell morphology or the expression of a microglial marker.
      Translocation of NF-kappaB to the nucleus also did not differ, nor did cytokine
      production. The levels of iNOS were also similar and, finally, microglia of
      either genotype showed no differences in either rates of phagocytosis or
      migration, even following activation. Thus, functional roles of PrP(C) in primary
      microglial cells are - if present - much more subtle than in transformed
      microglial cell lines. 

PMID- 26298320
TI  - The intracerebroventricular injection of rimonabant inhibits systemic
      lipopolysaccharide-induced lung inflammation.
AB  - We investigated the role of intracerebroventricular (ICV) injection of rimonabant
      (500ng), a CB1 antagonist, on lipopolysaccharide ((LPS) 5mg/kg)-induced pulmonary
      inflammation in rats in an isolated perfused lung model. There were decreases in
      pulmonary capillary pressure (Ppc) and increases in the ((Wet-Dry)/Dry lung
      weight)/(Ppc) ratio in the ICV-vehicle/LPS group at 4h. There were decreases in
      TLR4 pathway markers, such as interleukin receptor-associated kinase-1,
      IkappaBalpha, Raf1 and phospho-SFK (Tyr416) at 30min and at 4h increases in IL-6,
      vascular cell adhesion molecule-1 and myeloperoxidase in lung homogenate.
      Intracerebroventricular rimonabant attenuated these LPS-induced responses,
      indicating that ICV rimonabant modulates LPS-initiated pulmonary inflammation. 

PMID- 26298323
TI  - Circulating brain derived neurotrophic factor (BDNF) and frequency of BDNF
      positive T cells in peripheral blood in human ischemic stroke: Effect on outcome.
AB  - The aim of this study was to measure the levels of circulating BDNF and the
      frequency of BDNF-producing T cells after acute ischaemic stroke. Serum BDNF
      levels were measured by ELISA. Flow cytometry was used to enumerate peripheral
      blood leukocytes that were labelled with antibodies against markers of T cells, T
      regulatory cells (Tregs), and intracellular BDNF. There was a slight increase in
      serum BDNF levels after stroke. There was no overall difference between stroke
      patients and controls in the frequency of CD4(+) and CD8(+) BDNF(+) cells,
      although a subgroup of stroke patients showed high frequencies of these cells.
      However, there was an increase in the percentage of BDNF(+) Treg cells in the
      CD4(+) population in stroke patients compared to controls. Patients with high
      percentages of CD4(+) BDNF(+) Treg cells had a better outcome at 6months than
      those with lower levels. These groups did not differ in age, gender or initial
      stroke severity. Enhancement of BDNF production after stroke could be a useful
      means of improving neuroprotection and recovery after stroke. 

PMID- 26298322
TI  - Increased production of IL-17 in children with autism spectrum disorders and co
      morbid asthma.
AB  - Inflammation and asthma have both been reported in some children with autism
      spectrum disorder (ASD). To further assess this connection, peripheral immune
      cells isolated from young children with ASD and typically developing (TD)
      controls and the production of cytokines IL-17, -13, and -4 assessed following ex
      vivo mitogen stimulation. Notably, IL-17 production was significantly higher
      following stimulation in ASD children compared to controls. Moreover, IL-17 was
      increased in ASD children with co-morbid asthma compared to controls with the
      same condition. In conclusion, children with ASD exhibited a differential
      response to T cell stimulation with elevated IL-17 production compared to
      controls. 

PMID- 26298324
TI  - Vitamin D and estrogen synergy in Vdr-expressing CD4(+) T cells is essential to
      induce Helios(+)FoxP3(+) T cells and prevent autoimmune demyelinating disease.
AB  - Multiple sclerosis (MS) is a neurodegenerative disease resulting from an
      autoimmune attack on the axon-myelin unit. A female MS bias becomes evident after
      puberty and female incidence has tripled in the last half-century, implicating a
      female sex hormone interacting with a modifiable environmental factor. These
      aspects of MS suggest that many female MS cases may be preventable. Mechanistic
      knowledge of this hormone-environment interaction is needed to devise strategies
      to reduce female MS risk. We previously demonstrated that vitamin D3 (D3)
      deficiency increases and D3 supplementation decreases experimental autoimmune
      encephalomyelitis (EAE) risk in a female-biased manner. We also showed that D3
      acts in an estrogen (E2)-dependent manner, since ovariectomy eliminated and E2
      restored D3-mediated EAE protection. Here we probed the hypothesis that E2 and D3
      interact synergistically within CD4(+) T cells to control T cell fate and prevent
      demyelinating disease. The E2 increased EAE resistance in wild-type (WT) but not
      T-Vdr(0) mice lacking Vdr gene function in CD4(+) T cells, so E2 action depended
      entirely on Vdr(+)CD4(+) T cells. The E2 levels were higher in WT than T-Vdr(0)
      mice, suggesting the Vdr(+)CD4(+) T cells produced E2 or stimulated its
      production. The E2 decreased Cyp24a1 and increased Vdr transcripts in T cells,
      prolonging the calcitriol half-life and increasing calcitriol responsiveness. The
      E2 also increased CD4(+)Helios(+)FoxP3(+) T regulatory (Treg) cells in a Vdr
      dependent manner. Thus, CD4(+) T cells have a cooperative amplification loop
      involving E2 and calcitriol that promotes CD4(+)Helios(+)FoxP3(+) Treg cell
      development and is disrupted when the D3 pathway is impaired. The global decline
      in population D3 status may be undermining a similar cooperative E2-D3
      interaction controlling Treg cell differentiation in women, causing a breakdown
      in T cell self tolerance and a rise in MS incidence. 

PMID- 26298325
TI  - Effects of active immunisation with myelin basic protein and myelin-derived
      altered peptide ligand on pain hypersensitivity and neuroinflammation.
AB  - Neuropathic pain is a debilitating condition in multiple sclerosis and
      experimental autoimmune encephalomyelitis (EAE). Specific myelin basic protein
      (MBP) peptides are encephalitogenic, and myelin-derived altered peptide ligands
      (APLs) are capable of preventing and ameliorating EAE. We investigated the
      effects of active immunisation with a weakly encephalitogenic epitope of MBP
      (MBP87-99) and its mutant APL (Cyclo-87-99[A(91),A(96)]MBP87-99) on pain
      hypersensitivity and neuroinflammation in Lewis rats. MBP-treated rats exhibited
      significant mechanical and thermal pain hypersensitivity associated with
      infiltration of T cells, MHC class II expression and microglia activation in the
      spinal cord, without developing clinical signs of paralysis. Co-immunisation with
      APL significantly decreased pain hypersensitivity and neuroinflammation
      emphasising the important role of neuroimmune crosstalk in neuropathic pain. 

PMID- 26298326
TI  - Toll-like receptor-3 gene polymorphism in patients with Japanese encephalitis.
AB  - INTRODUCTION: Japanese encephalitis (JE) is one of the most lethal mosquito-borne
      viral encephalitis seen in India. Toll-like receptors (TLRs) play a critical role
      in host defence mechanism against flaviviruses causing encephalitis. We assessed
      whether abnormalities in toll-like receptor (TLR3) increase the susceptibly for
      JE. METHOD: A total of 103 JE patients (all from an endemic area) and 103 healthy
      control subjects were examined for TLR3 Leu412Phe polymorphism with the help of
      polymerase chain reaction (PCR) and genetic sequencing method. RESULTS: A
      significantly higher frequency of Leu412Phe polymorphism was noted in JE patients
      as compared with healthy controls [mutant (TT) genotype, P-value=0.019; mutant
      (TT)+heterozygous (CT) genotype, P-value=0.013]. Furthermore, frequency of 412Phe
      allele (T) of TLR3 gene was significantly higher in patients with JE than in
      controls (P-value=0.001). There was no significant difference in the distribution
      of any of the TLR3 Leu412Phe (L412F) polymorphism genotype with death within
      1month. CONCLUSION: TLR3 gene polymorphism might confer host genetic
      susceptibility to JE in Indian population. TLR3 polymorphism did not affect the
      mortality.

PMID- 26298327
TI  - Comment on "In vivo and systems biology studies implicate IL-18 as a central
      mediator in chronic pain" by Vasudeva et al., J. Neuroimmunol. 2015 June; 283:3
      49.

PMID- 26298328
TI  - Psychotic syndrome associated with anti-Ca/ARHGAP26 and voltage-gated potassium
      channel antibodies.
AB  - BACKGROUND: Antibodies to the Rho GTPase-activating protein 26 (ARHGAP26, GRAF1)
      (also termed anti-Ca) were first described in patients with cerebellar ataxia.
      However, ARHGAP26 is also expressed in some hippocampal neurons. Moreover, some
      of the previously reported patients showed cognitive and affective symptoms. It
      is unknown whether those symptoms reflected involvement of the limbic system or
      were part of the so-called cerebellar cognitive/affective syndrome. CASE REPORT:
      Here, we report a newly diagnosed anti-Ca/ARHGAP26-IgG-positive patient who
      presented with recurrent psychotic symptoms but no cerebellar ataxia. In
      addition, low-titer acetylcholine receptor antibodies, voltage-gated potassium
      channel complex antibodies (but no LGI1 or CASPR2 antibodies) and anti-nuclear
      antibodies of unknown specificity were detected, suggesting a general autoimmune
      predisposition. Thymectomy revealed mild thymic nodular hyperplasia. CONCLUSION:
      This case indicates that the clinical spectrum of ARHGAP26-related autoimmunity
      might be broader than expected. Studies on the prevalence of anti-Ca/ARHGAP26 in
      patients with suspected limbic encephalitis seem warranted.

PMID- 26298329
TI  - Increased neutralization capacity of TNF-alpha in sera of relapsing remitting
      multiple sclerosis patients is not related to soluble TNF-alpha receptors or anti
      TNF-alpha autoantibody levels.
AB  - The increased TNF-alpha levels in active lesions and CSF of multiple sclerosis
      (MS) patients and the beneficial effect of TNF-alpha blockade in animal models of
      MS led to the therapeutic usage of TNF-alpha antagonists. However, systemic TNF
      alpha blockade exacerbated MS activity and was associated with new-onset MS when
      implemented for treating other autoimmune disorders. We employed a TNF-alpha
      neutralization bioassay and demonstrated that the capacity of sera from untreated
      and IFN-beta-treated relapsing remitting MS patients to neutralize TNF-alpha is
      significantly higher than that of matched healthy controls. This finding was not
      related to sTNFRI, sTNFRII, or anti-TNF-alpha Abs levels. 

PMID- 26298330
TI  - Antibodies to dendritic neuronal surface antigens in opsoclonus myoclonus ataxia
      syndrome.
AB  - Opsoclonus myoclonus ataxia syndrome (OMAS) is an autoimmune disorder
      characterized by rapid, random, conjugate eye movements (opsoclonus), myoclonus,
      and ataxia. Given these symptoms, autoantibodies targeting the cerebellum or
      brainstem could mediate the disease or be markers of autoimmunity. In a subset of
      patients with OMAS, we identified such autoantibodies, which bind to non-synaptic
      puncta on the surface of live cultured cerebellar and brainstem neuronal
      dendrites. These findings implicate autoimmunity to a neuronal surface antigen in
      the pathophysiology of OMAS. Identification of the targeted antigen(s) could
      elucidate the mechanisms underlying OMAS and provide a biomarker for diagnosis
      and response to therapy. 

PMID- 26298332
TI  - "Chemsex" and harm reduction need among gay men in South London.
AB  - BACKGROUND: Chemsex is a colloquial term used by gay men in some parts of the UK
      to describe the use of psychoactive substances (typically mephedrone, GHB/GBL or
      crystal methamphetamine) during sex. Use of these drugs by gay men in London
      appears to have risen sharply from relatively low levels and, as yet, there is
      little data to inform appropriate harm reduction services. This study sought to
      understand the personal and social context of chemsex and the nature of harm
      reduction need. METHODS: In-depth interviews were conducted with 30 self
      identifying gay men (age range 21-53) who lived in three South London boroughs,
      and who had used either crystal methamphetamine, mephedrone or GHB/GBL either
      immediately before or during sex with another man during the previous 12 months.
      Data were subjected to a thematic analysis. RESULTS: While around half of
      participants had utilised a range of drugs over many years, others had only
      recently been introduced to drugs, often by sexual partners who wished to enhance
      the sexual session. As relatively new drugs on the gay scene, understanding of
      appropriate dosing was lacking and a majority described overdoses, particularly
      in relation to GHB/GBL. Negotiation of sex, especially in group sex environments,
      was complicated by the effects of the drugs and a small number of men reported
      concerns relating to sexual consent. While a significant proportion of men had
      experienced a range of physical and mental health harms, few had accessed
      professional support for fear of judgement or concern about chemsex expertise.
      CONCLUSION: Findings from this study indicate a substantial degree of harm in the
      usage of relatively new psychoactive substances in highly sexual circumstances.
      Generic drug services, typically designed to address the needs of opiate users,
      may not be sufficiently resourced to address the specific and acute needs of gay
      men engaging in chemsex.

PMID- 26298331
TI  - Hepatitis C virus (HCV) disease progression in people who inject drugs (PWID): A
      systematic review and meta-analysis.
AB  - BACKGROUND: Understanding HCV disease progression rates among people who inject
      drugs (PWID) is important to setting policy to expand access to detection,
      diagnosis and treatment, and in forecasting the burden of disease. In this paper
      we synthesize existing data on the natural history of HCV among PWID, including
      fibrosis progression rates (FPR) and the incidence of compensated cirrhosis (CC),
      decompensated cirrhosis (DC), and hepatocellular carcinoma (HCC). METHODS: We
      conducted electronic and manual searches for published and unpublished
      literature. Reports were eligible if they (i) included participants who were
      chronically infected with HCV and reported current or previous injection drug
      use; (ii) presented original data on disease progression in a study sample
      comprised of at least 90% PWID; (iii) published between January 1, 1990, and
      December 31, 2013; and (iv) included data from upper-middle- or high-income
      countries. Quality ratings were assigned using an adaptation of the Quality In
      Prognosis Studies (QUIPS) tool. We estimated pooled FPRs using the stage-constant
      and stage-specific methods, and pooled incidence rates of CC, DC, and HCC.
      RESULTS: Twenty-one reports met the study inclusion criteria. Based on random
      effect models, the pooled stage-constant FPR was 0.117 METAVIR units per year
      (95% CI, 0.099-0.135), and the stage-specific FPRs were F0->F1, 0.128 (95% CI
      0.080, 0.176); F1->F2, 0.059 (95% CI 0.035, 0.082); F2->F3, 0.078 (95% CI 0.056,
      0.100); and F3->F4, 0.116 (95% CI 0.070, 0.161). The pooled incidence rates of
      CC, DC, and HCC were 6.6 (95% CI 4.8, 8.4), 1.1 (95% CI 0.8, 1.4), and 0.3 (95%
      CI -0.1, 0.6) events per 1000 person-years, respectively. Following the stage
      constant estimate, average time to cirrhosis is 34 years post-infection, and time
      to METAVIR stage F3 is 26 years; using the stage-specific estimates, time to
      cirrhosis is 46 years and time to F3 is 38 years. CONCLUSION: Left untreated,
      PWID with chronic HCV infection will develop liver sequelae (including HCC) in
      mid- to late-adulthood. Delaying treatment with the new drug regimens until
      advanced fibrosis develops prolongs the period of infectiousness to perhaps
      thirty years. Scaling up of effective HCV prevention and early engagement in care
      and treatment will facilitate the elimination HCV as a source of serious disease
      in PWID.

PMID- 26298333
TI  - Clinical efficacy of denosumab versus bisphosphonates for the prevention of bone
      complications: implications for nursing.
AB  - Antiresorptive therapies are used for the prevention of skeletal-related events
      (SREs) associated with metastatic bone disease related to breast cancer, prostate
      cancer, and other solid tumors. This review highlights the central role of nurses
      in supporting and educating advanced cancer patients regarding the consequences
      of bone metastases and SREs, including therapy management options. Contemporary
      clinical journals reporting evidence-based studies were reviewed. SREs associated
      with bone metastases can significantly impact the quality of life of advanced
      cancer patients. Denosumab therapy, an advancement in antiresorptive treatments,
      significantly prevents and delays the time to develop SREs. In the multifaceted
      approach required for successful and consistent management of SREs associated
      with bone metastases, antiresorptive therapies can play a central role in
      maintaining the functional independence of patients through the prevention of
      debilitating SREs, thereby preserving quality of life. 

PMID- 26298334
TI  - Zoledronic acid for treatment of osteopenia and osteoporosis in women with
      primary breast cancer undergoing adjuvant aromatase inhibitor therapy: a 5-year
      follow-up.
AB  - PURPOSE: This study was designed to explore whether zoledronic acid could prevent
      expected loss of bone mineral density (BMD) in postmenopausal women with pre
      existing osteopenia or osteoporosis who were initiating adjuvant letrozole
      therapy for primary breast cancer. METHODS: Between June 2006 and July 2007, 60
      postmenopausal women with estrogen and/or progesterone receptor-positive breast
      cancer and a BMD T-score <=-2.0 were enrolled. Participants received letrozole
      2.5 mg and vitamin D 400 IU daily, calcium 500 mg twice daily, and zoledronic
      acid 4 mg every 6 months for a maximum of 5 years or until disease progression.
      BMD at the lumbar spine and femoral neck was recorded at the start of the study
      and annually for 5 years. Patients were evaluated for fractures every 6 months
      for the duration of the trial. RESULTS: After 5 years, mean BMD increased
      significantly by 11.6% (p = 0.01) at the lumbar spine and by 8.8% (p = 0.01) at
      combined sites. Femoral neck BMD increased by 4.2%, although this was not
      significant (p = 0.23). At the end of the trial, BMDs were consistent with
      osteoporosis in 7 % and osteopenia in 36% of the patients. A total of six
      fractures were reported after 417 individual assessments. CONCLUSIONS: Zoledronic
      acid appears to prevent further bone loss in postmenopausal breast cancer
      patients with osteopenia and osteoporosis starting treatment with letrozole.
      These findings were maintained at 5 years and support concurrent initiation of
      bisphosphonate and aromatase inhibitor therapy in this high-risk population.

PMID- 26298335
TI  - Response to editorial by Richard Crevenna, MD, regarding "cancer rehabilitation
      and palliative care: critical components in the delivery of high-quality oncology
      services" by Silver et al.

PMID- 26298336
TI  - Atmospheric mercury deposition and its contribution of the regional atmospheric
      transport to mercury pollution at a national forest nature reserve, southwest
      China.
AB  - Atmospheric mercury deposition by wet and dry processes contributes to the
      transformation of mercury from atmosphere to terrestrial and aquatic systems.
      Factors influencing the amount of mercury deposited to subtropical forests were
      identified in this study. Throughfall and open field precipitation samples were
      collected in 2012 and 2013 using precipitation collectors from forest sites
      located across Mt. Jinyun in southwest China. Samples were collected
      approximately every 2 weeks and analyzed for total (THg) and methyl mercury
      (MeHg). Forest canopy was the primary factor on THg and MeHg deposition.
      Simultaneously, continuous measurements of atmospheric gaseous elemental mercury
      (GEM) were carried out from March 2012 to February 2013 at the summit of Mt.
      Jinyun. Atmospheric GEM concentrations averaged 3.8 +/- 1.5 ng m(-3), which was
      elevated compared with global background values. Sources identification indicated
      that both regional industrial emissions and long-range transport of Hg from
      central, northeast, and southwest China were corresponded to the elevated GEM
      levels. Precipitation deposition fluxes of THg and MeHg in Mt. Jinyun were
      slightly higher than those reported in Europe and North America, whereas total
      fluxes of MeHg and THg under forest canopy on Mt. Jiuyun were 3 and 2.9 times of
      the fluxes of THg in wet deposition in the open. Highly elevated litterfall
      deposition fluxes suggest that even in remote forest areas of China, deposition
      of atmospheric Hg(0) via uptake by vegetation leaf may be a major pathway for the
      deposition of atmospheric Hg. The result illustrates that areas with greater
      atmospheric pollution can be expected to have greater fluxes of Hg to soils via
      throughfall and litterfall.

PMID- 26298337
TI  - Polonium-210 levels in different environmental samples.
AB  - Polonium-210 is analysed in different samples which can be affected by the
      presence of a dicalcium phosphate plant (DCP). Particularly, it was determined in
      sludge samples from a drinking water treatment plant located downstream of the
      phosphate plant. From the obtained results, it was not possible to establish a
      correlation with the industrial activities carried out in the DCP plant since the
      measured activities were comparable to the reported in the literature for normal
      soils. This isotope was also monitored in different biota species (as mussels)
      taken also downstream of the DCP, and the potential risk of their ingestion by
      calculating the total effective doses was evaluated. As a result, it is important
      to highlight that the ingestion of these mussels does not constitute a risk for
      the population since the found doses were lower than the values published by
      UNSCEAR. 

PMID- 26298338
TI  - Short-term exposure to particulate air pollution and risk of myocardial
      infarction: a systematic review and meta-analysis.
AB  - A growing number of studies have associated short-term exposure to ambient
      particulate matter air pollution (PM) and risk of specific cardiovascular events,
      just as myocardial infarction (MI). However, the results of the recent studies
      were inconsistent; therefore, a systematic review and meta-analysis was
      performed. To synthetically quantify the association between short-term exposure
      to PM and risk of MI, a meta-analysis was conducted to combine the estimates of
      effect for a relationship between short-term exposure to PM10, PM2.5 (particulate
      matter <= 10 MUm, 2.5 MUm in diameter) and risk of MI. Electronic database
      searches for all relevant published studies were updated in January 2015. And, a
      random-effects model was performed to estimate pooled relative risk (RR) and 95 %
      confidence intervals (95 % CI). Thirty-one published observational
      epidemiological studies were identified. Risk of MI was significantly associated
      with per 10 MUg/m(3) increment in PM10 (OR = 1.005; 95 % CI 1.001-1.008) and
      PM2.5 (OR = 1.022; 95 % CI 1.015-1.030). The risk of PM2.5 exposure was
      relatively greater than PM10. In the subgroup analysis by study design, location,
      quality score, and lag exposure, the results were basically consistent with the
      former overall results in PM2.5 but slightly changed in PM10. Short-term exposure
      to particulate matter (PM2.5, PM10) was a risk factor for MI, and the results
      further confirmed the discovery in the previous meta-analysis.

PMID- 26298339
TI  - Hydrogen storage studies on palladium-doped carbon materials (AC, CB, CNMs) @
      metal-organic framework-5.
AB  - Metal organic frameworks (MOFs) are a rapidly growing class of porous materials
      and are considered as best adsorbents for their high surface area and
      extraordinary porosity. The MOFs are synthesized by using various chemicals like
      triethylamine, terepthalic acid, zinc acetate dihydrate, chloroform, and
      dimethylformamide (DMF). Synthesized MOFs are intercalated with
      palladium/activated carbon, carbon black, and carbon nanomaterials by chemical
      reduction method for the purpose of enhancing the hydrogen adsorption capacities.
      We have observed that the palladium doped activated carbon on MOF-5 showed high
      hydrogen storage capacity. This may be due to the affinity of the palladium
      toward hydrogen molecule. The samples are characterized by X-ray diffraction,
      scanning electron microscopy (SEM), and Brunauer-Emmett-Teller (BET) surface area
      analysis. We have observed a clear decrease in the BET surface area and pore
      volume. The obtained results show a better performance for the synthesized
      sample. To our best knowledge, no one has reported the work on palladium-doped
      carbon materials (activated carbon, carbon black, carbon nanomaterials)
      impregnated to the metal-organic framework-5. We have attempted to synthesize
      carbon nanomaterials using indigenously fabricated chemical vapor deposition
      (CVD) unit as a support. We have observed an increase in the hydrogen storage
      capacities. 

PMID- 26298340
TI  - Long-term performance of vertical-flow and horizontal-flow constructed wetlands
      as affected by season, N load, and operating stage for treating nitrogen from
      domestic sewage.
AB  - To investigate the long-term nitrogen treatment efficiency in vertical-flow (VF)
      horizontal-flow (HF) hybrid constructed wetlands (CWs), the nitrogen removal
      efficiency under different seasons, N loads, and three operating stages
      (representing age of the wetland) were evaluated over a 12-year period. The
      average total nitrogen (TN) removal efficiencies in the effluent during the
      operation period were in the following order: summer (75.2%) > spring (73.4%) ?
      autumn (72.6%) > winter (66.4%). The removal efficiencies of TN in summer,
      autumn, and spring were generally higher than those in winter. At different
      stages of operation (years), the average TN removal rates in the effluent were in
      the following order: middle stage (73.4%; years 2006-2009) > last stage (72.0%;
      years 2010-2013) > beginning stage (70.1%; years 2002-2005). In VF-HF CWs, the
      amount of average TN removal (mg N m(-2) day(-1)) over the 12-year period was in
      the order of summer (5.5) ? autumn (5.1) > spring (4.3) ? winter (4.2) for the VF
      bed and in the order of summer (3.5) ? spring (3.5) ? autumn (3.3) > winter (2.7)
      for the HF bed, showing that the amount of TN removal per unit area (m(2)) in
      summer was slightly greater than that in other seasons. The amount of TN removal
      in the VF bed was slightly greater than that in the HF bed. Using three
      dimensional simulation graphs, the maximum TN removal rate was at inflow N loads
      below 2.7 g m(-2) day(-1) in the summer season, whereas the minimum TN removal
      rate was at inflow N loads below 1.4 g m(-2) day(-1) in the winter season.
      Consequently, the TN removal efficiency was very stable over the 12 years of
      operation in VF-HF hybrid CWs. Results demonstrate that the VF-HF hybrid CWs
      possess good buffer capacity for treating TN from domestic sewage for extended
      periods of time.

PMID- 26298341
TI  - Enhanced bioremediation of BTEX contaminated groundwater in pot-scale wetlands.
AB  - Pot-scale wetlands were used to investigate the role of plants in enhancing the
      performance of engineered bioremediation techniques like biostimulation,
      bioaugmentation, and phytoremediation collectively. Canna generalis plants were
      grown hydroponically in BTEX contaminated groundwater supplied in wetland
      mesocosms. To quantify the contaminant uptake by the plants, wetlands with and
      without shoot biomass along with unplanted gravel bed were used under controlled
      conditions. The residual concentration of the selected BTEX compound, toluene, in
      the rhizosphere water was measured over the entire period of the experiment along
      with the water lost by evapotranspiration. The rate of biodegradation in all
      wetland mesocosms fitted best with the first-order kinetics. The total removal
      time of the BTEX compound was found to be highest in the unplanted gravel bed
      mesocosm followed by wetlands without and with shoot biomass. The cumulative
      uptake of toluene in shoot biomass of the wetland plants initially increased
      rapidly and started to decrease subsequently till it reached a peak value.
      Continuity equations integrated with biodegradation and plant uptake sink terms
      were developed to simulate residual concentration of toluene in rhizospheric
      water for comparison with the measured data for entire period of the experiments.
      The results of this research can be used to frame in situ plant-assisted
      bioremediation techniques for hydrocarbon-contaminated soil-water resources. 

PMID- 26298342
TI  - Assessment of palladium footprint from road traffic in two highway environments.
AB  - Palladium (Pd) is an emerging eco-toxic pollutant from vehicle catalytic
      converters, emitted worldwide for more than two decades. Nowadays, the spatial
      extent of Pd fallout is growing along roads, but its subsequent fate in
      neighboring terrestrial ecosystems has not been extensively addressed yet. Two
      sites representative of contrasted natural environments (field, forest) but
      located under similar ambient conditions were selected to isolate and analyze the
      specific impact of vehicular Pd, along highway A71, France. Pd impregnation was
      assessed along 200-m-long transects perpendicular to the highway. Contents were
      measured in soils, earthworms, plant communities of the right of way (ROW), and
      the neighboring field (crop weeds), as well as in a moss, and bramble and ivy
      leaves in the forest. The direct impact of Pd fallouts appears to be confined in
      the grassy verge of the highway: ROW soils ([Pd] = 52-65 ng g(-1)), earthworms
      ([Pd] = 18-38 ng g(-1)), and plant community ([Pd] = 10-23 ng g(-1)). Pd
      footprint is pointed out by the accumulation index calculated for earthworms and
      plant communities even though transfer coefficients indicate the absence of
      bioaccumulation (TCs < 1). An indirect longer range transfer of Pd is identified,
      induced by hydric transport of organic matter.

PMID- 26298344
TI  - Visual asymmetries for relative depth judgments in a three-dimensional space.
AB  - Our ability to process information about an object's location in depth varies
      along the horizontal and vertical axes. These variations reflect functional
      specialisation of the cerebral hemispheres as well as the ventral/dorsal visual
      streams for processing stimuli located in near and far space. Prior research has
      demonstrated visual field superiorities for processing near space in the lower
      and right hemispaces and for far space in the upper and left hemispaces. No
      research, however, has directly tested whether the functional specialisation of
      the visual fields actually makes objects look closer when presented in the lower
      or right visual fields. To measure biases in the perception of depth, we employed
      anaglyph stimuli where participants made closer/further judgments about the
      relative location of two spheres in a three-dimensional virtual space. We
      observed clear processing differences in this task where participants perceived
      the right and lower spheres to be closer and the left and upper spheres to be
      further away. Furthermore, no relationship between the horizontal and vertical
      dimensions was observed suggesting separate cognitive/neural mechanisms. Not only
      does this methodology clearly demonstrate differences in perceived depth across
      the visual field, it also opens up many possibilities for studying functional
      asymmetries in three-dimensional space. 

PMID- 26298343
TI  - Effects of poultry manure on soil biochemical properties in phthalic acid esters
      contaminated soil.
AB  - This study aimed to evaluate the effects of poultry manure (PM) on soil
      biological properties in DBP- and DEHP-contaminated soils. An indoor incubation
      experiment was conducted. Soil microbial biomass C (Cmic), soil enzymatic
      activities, and microbial phospholipid fatty acid (PLFA) concentrations were
      measured during incubation period. The results indicated that except alkaline
      phosphatase activity, DBP and DEHP had negative effects on Cmic, dehydrogenase,
      urease, protease activities, and contents of total PLFA. However, 5 % PM
      treatment alleviated the negative effects of PAEs on the above biochemical
      parameters. In DBP-contaminated soil, 5 % PM amendment even resulted in
      dehydroenase activity and Cmic content increasing by 17.8 and 11.8 % on the day
      15 of incubation, respectively. During the incubation periods, the total PLFA
      contents decreased maximumly by 17.2 and 11.6 % in DBP- and DEHP-contaminated
      soils without PM amendments, respectively. Compared with those in uncontaminated
      soil, the total PLFA contents increased slightly and the value of
      bacPLFA/fugalPLFA increased significantly in PAE-contaminated soils with 5 % PM
      amendment. Nevertheless, in both contaminated soils, the effects of 5 % PM
      amendment on the biochemical parameters were not observed with 10 % PM amendment.
      In 10 % PM-amended soils, DBP and DEHP had little effect on Cmic, soil enzymatic
      activities, and microbial community composition. At the end of incubation, the
      effects of PAEs on these parameters disappeared, irrespective of PM amendment.
      The application of PM ameliorated the negative effect of PAEs on soil biological
      environment. However, further work is needed to study the effect of PM on soil
      microbial gene expression in order to explain the change mechanisms of soil
      biological properties.

PMID- 26298345
TI  - Taking a Giant Step Toward Women's Heart Health: Finding Policy Solutions to
      Unanswered Research Questions.

PMID- 26298346
TI  - miRNA-204 drives cardiomyocyte proliferation via targeting Jarid2.
AB  - OBJECTIVES: In mammals, the heart grows by hypertrophy but not proliferation of
      cardiomyocytes after birth. The paucity of cardiomyocyte proliferation limits
      cardiac regeneration in a variety of heart diseases. To explore the efficient
      strategies that drive cardiomyocyte proliferation, we employed in vitro and in
      vivo models to investigate the function of miRNA-204, which was demonstrated to
      regulate the proliferation and differentiation of human cardiac progenitor cells
      in our previous study. METHODS AND RESULTS: miRNA-204 overexpression markedly
      promoted cardiomyocyte proliferation in both neonatal and adult rat
      cardiomyocytes in vitro. Transgenic mice with the cardiac-specific overexpression
      of miRNA-204 exhibited excessive cardiomyocyte proliferation throughout the
      embryonic and adult stages, leading to a pronounced increase in ventricular mass.
      Accordingly, the cell cycle regulators, including Cyclin A, Cyclin B, Cyclin D2,
      Cyclin E, CDC2 and PCNA, were upregulated in miRNA-204 transgenic embryonic
      hearts. Furthermore, we demonstrated that miRNA-204 directly targeted Jarid2.
      Knockdown of Jarid2 mimicked the pro-proliferative effect of miRNA-204
      overexpression on cultured rat cardiomyocytes, whereas enhanced expression of
      Jarid2 conferred the myocytes with substantial resistance to proliferation by
      miRNA-204 overexpression. CONCLUSION: Our findings identify a conserved role for
      miRNA-204 in regulating cardiomyocyte proliferation by targeting the Jarid2
      signaling pathway.

PMID- 26298347
TI  - Electrocardiograms in patients with ST-elevation myocardial infarction, non-ST
      elevation myocardial infarction, and Takotsubo syndrome.

PMID- 26298348
TI  - Cardiac positron emission tomography imaging with quantification of
      fluorodeoxyglucose for the detection of cardiac sarcoidosis.

PMID- 26298349
TI  - Coronary artery fistula causing angina pectoris after cardiac surgery - An
      interesting pathophysiologic link.

PMID- 26298351
TI  - Effects of PPARgamma agonist on heart rate variability and cardiac mitochondrial
      function in obese-insulin resistant rats.

PMID- 26298350
TI  - Which biomarkers are predictive specifically for cardiovascular or for non
      cardiovascular mortality in men? Evidence from the Caerphilly Prospective Study
      (CaPS).
AB  - OBJECTIVE: To examine a panel of 28 biomarkers for prediction of cardiovascular
      disease (CVD) and non-CVD mortality in a population-based cohort of men. METHODS:
      Starting in 1979, middle-aged men in Caerphilly underwent detailed medical
      examination. Subsequently 2171 men were re-examined during 1989-1993, and fasting
      blood samples obtained from 1911 men (88%). Fibrinogen, viscosity and white cell
      count (WCC), routine biochemistry tests and lipids were analysed using fresh
      samples. Stored aliquots were later analysed for novel biomarkers. Statistical
      analysis of CVD and non-CVD mortality follow-up used competing risk Cox
      regression models with biomarkers in thirds tested at the 1% significance level
      after covariate adjustment. RESULTS: During an average of 15.4 years follow-up,
      troponin (subhazard ratio per third 1.71, 95% CI 1.46-1.99) and B-natriuretic
      peptide (BNP) (subhazard ratio per third 1.54, 95% CI 1.34-1.78) showed strong
      trends with CVD death but not with non-CVD death. WCC and fibrinogen showed
      similar weaker findings. Plasma viscosity, growth differentiation factor 15 (GDF
      15) and interleukin-6 (IL-6) were associated positively with both CVD death and
      non-CVD death while total cholesterol was associated positively with CVD death
      but negatively with non-CVD death. C-reactive protein (C-RP), alkaline
      phosphatase, gamma-glutamyltransferase (GGT), retinol binding protein 4 (RBP-4)
      and vitamin B6 were significantly associated only with non-CVD death, the last
      two negatively. Troponin, BNP and IL-6 showed evidence of diminishing
      associations with CVD mortality through follow-up. CONCLUSION: Biomarkers for
      cardiac necrosis were strong, specific predictors of CVD mortality while many
      inflammatory markers were equally predictive of non-CVD mortality.

PMID- 26298352
TI  - Comparison of four nontraditional lipid profiles in relation to ischemic stroke
      among hypertensive Chinese population.

PMID- 26298353
TI  - Fluoroless catheter ablation of intraatrial reentrant tachycardia status post
      Fontan procedure: Fluoroless catheter ablation in Fontan patient.

PMID- 26298354
TI  - Absorb bioresorbable vascular scaffold: What have we learned after 5 years of
      clinical experience?
AB  - Bioresorbable scaffolds have the potential to introduce a paradigm shift in
      interventional cardiology, a true anatomical and functional "vascular
      restoration" instead of an artificial stiff tube encased by persistent metallic
      foreign body. Early clinical studies using the first commercially available drug
      eluting bioresorbable vascular scaffold (BVS) reported very promising safety and
      efficacy outcomes, comparable to best-in-class second-generation drug-eluting
      metal stent. To date, more than 60,000 Absorb BVSs have been implanted with only
      the interim analysis of one randomized trial (ABSORB II RCT) available. Recent
      registries have challenged the initial claim that BVS is immune from Scaffold
      Thrombosis (ST). However, suboptimal device expansion and insufficient
      intracoronary imaging guidance can explain higher than expected ST, especially in
      complex lesions. The aim of this review article is to critically evaluate the
      results of the available Absorb BVS studies and discuss the lessons learned to
      optimize lesion selection and implantation technique of such devices. 

PMID- 26298355
TI  - First in man closure of a fenestrated ventricular septal defect (VSD) with a new
      paravalvular leak device (Occlutech PLD).

PMID- 26298356
TI  - The role of media on statin adherence.

PMID- 26298357
TI  - Renal sympathetic denervation: A potential alternative strategy for managing
      patients with heart failure.

PMID- 26298358
TI  - Low-intensity exercise under ischemic conditions enhances metabolic stress in
      patients with heart failure.

PMID- 26298359
TI  - Use of (18)F-FDG PET and MPI with (99m)Tc-MIBI in a patient with delayed
      diagnosis of homozygous familial hypercholesterolemia.

PMID- 26298360
TI  - The role of P-wave indices in the diagnosis of emphysema.

PMID- 26298361
TI  - Prevalence of elevated blood pressure is associated with the increasing
      prevalence of obesity among children and adolescents in Shandong, China.

PMID- 26298362
TI  - Combination refusion therapy for a hemodynamically unstable patient with acute
      myocardial infarction complicated by acute ischemic stroke within a time window.

PMID- 26298363
TI  - Preoperative physical activity in relation to postoperative delirium in elective
      cardiac surgery patients.

PMID- 26298364
TI  - A rapid decrease of the medical college applicants in China this year.

PMID- 26298365
TI  - Retrograde externalization of a Floppy RotaWire in a chronic total occlusion.

PMID- 26298366
TI  - Comment on antidepressant use in cardiovascular diseases.

PMID- 26298367
TI  - The reverse accordion effect.

PMID- 26298368
TI  - Anomalous origin of the left coronary artery from the pulmonary trunk.

PMID- 26298369
TI  - Non-response to questionnaires independently predicts mortality of coronary
      angiography patients.

PMID- 26298370
TI  - Difference in autonomic nervous activity in different subtypes of
      noncardioembolic ischemic stroke.

PMID- 26298371
TI  - Reduced dobutamine stress test-based coronary flow reserve in patients with
      Takotsubo syndrome: An innate substrate or a lingering effect?

PMID- 26298372
TI  - Increased health service use for pulmonary embolism in men: Northumbrian hospital
      episode statistics, 2013-2014.

PMID- 26298373
TI  - Impact of greater than 12-month dual antiplatelet therapy duration on mortality:
      Drug-specific or a class-effect? A meta-analysis.

PMID- 26298374
TI  - Pharmacotherapeutic considerations for the treatment of thyrotoxic pericarditis.

PMID- 26298375
TI  - Dual infection with S. pneumoniae and M. tuberculosis was also a possibility.

PMID- 26298376
TI  - Increased health service use for hypotension in the very old: Northumbrian
      hospital episode statistics, 2013-2014.

PMID- 26298377
TI  - Embolism from noncompaction to different vascular territories.

PMID- 26298378
TI  - Edema index measured by bioelectrical impedance analysis as a predictor of fluid
      reduction needed to remove clinical congestion in acute heart failure.

PMID- 26298379
TI  - Recovering sinus rhythm by fine adjustments of an Amplatzer duct occluder after
      ventricular septal defect closure.

PMID- 26298380
TI  - Sex differences in clinical characteristics and inpatient outcomes among 2442
      hospitalized Chinese patients with nonvalvular atrial fibrillation: The Nanchang
      Atrial Fibrillation Project.
AB  - BACKGROUND: Limited data exists on the impact of sex on clinical characteristics
      and outcomes among nonvalvular AF patients from China. We investigated the impact
      of gender on risk factors and inpatient mortality in a hospitalized nonvalvular
      AF cohort in Nanchang, China. METHODS: We studied consecutive patients
      hospitalized with nonvalvular AF between May 2011 and December 2013. Predictors
      of inpatient mortality were evaluated using multivariate regression analyses.
      RESULTS: We studied 2442 patients (43.7% female; mean age 71.8), with a median
      hospital stay of 10 days (IQR: 7-14). Inpatient mortality was 2.2%. Mean age,
      CHADS2 and CHA2DS2-VASc scores were higher in females vs. males (all p<0.0001).
      Oral anticoagulation use during hospitalization was 33.3% without sex
      differences, and length of stay and inpatient outcomes were comparable between
      sexes. On multivariate analyses, the significant risk factors of inpatient death
      in females were previous ischemic stroke/transient ischemic attack
      (TIA)/thromboembolism (TE) (Odds Ratio (OR): 2.27; 95% Confidence Intervals (CI):
      1.43-3.61), peripheral artery disease (OR: 5.75, 95% CI: 1.49-22.16) and chronic
      renal disease (OR: 5.68, 95% CI: 1.46-22.13). Among males, only age (OR: 1.06,
      95% CI: 1.02-1.11) and previous ischemic stroke/TIA/TE (OR: 1.81, 95% CI: 1.25
      2.63) were independent predictors of inpatient mortality. CONCLUSION: Sex related
      differences in clinical characteristics and stroke risk profile were evident in
      Chinese nonvalvular AF patients, but no sex disparity was evident in the low
      antithrombotic therapy use or inpatient mortality. Previous ischemic
      stroke/TIA/TE was an important predictor of inpatient mortality in both female
      and male patients.

PMID- 26298382
TI  - Mass attached to mechanical mitral valve mimicking a thrombus.
AB  - Mitral valve replacement with preservation of chordae tendineae and papillary
      muscles is a well-known technique which has proved beneficial by reducing
      postoperative left ventricular remodeling and preserving left ventricular
      function. This advantage has been demonstrated in functional mitral valve
      regurgitation as well as mitral valve regurgitation due to rheumatic disease.
      Regarding complications of this technique, several of them have been reported,
      papillary muscle rupture being one of them. We describe a clinical case of this
      weird but possible kind of complication. 

PMID- 26298381
TI  - Unresolved issues in the management of chronic stable angina.
AB  - Chronic stable angina is a common and progressive disease which has a major
      impact on patient quality of life and imposes a high financial and medical burden
      on society. Given the range of agents now available, optimal medical therapy -
      which according to guidelines is the preferred option in the majority of patients
      with low-risk disease - offers the opportunity for effective control. However,
      recent studies suggest that management remains suboptimal in up to a third of
      patients and that physicians often underestimate the extent to which angina
      continues to limit patients' lives. A higher frequency of angina also relates
      directly to increased healthcare costs. These factors suggest the need for the
      development and implementation of appropriate guidelines, for tools to encourage
      the regular, systematic assessment of the management of chronic stable angina
      patients, and for improved means of communication between doctors and patients.
      Neither physicians nor their patients need to accept that a certain level of
      angina symptoms is unavoidable. 

PMID- 26298383
TI  - Catheter ablation of idiopathic fascicular ventricular tachycardia: The role of
      isolated diastolic potentials during mapping in sinus rhythm.

PMID- 26298384
TI  - Guidezilla guide extension catheter facilitated the delivery of long and bulky
      In.Pact Falcon drug-coated balloon for the treatment of chronic total occlusion
      lesion.

PMID- 26298385
TI  - Recurrent ventricular fibrillation in a young female carrying a previously
      unidentified RyR2 gene mutation.

PMID- 26298386
TI  - Deciphering synergistic characteristics of microbial fuel cell-assisted dye
      decolorization.
AB  - This study provided a novel evaluation scheme to quantitatively reveal
      "synergistic" stimulation of microbial fuel cell (MFC)-assisted dye
      decolorization for industrial practicability. This work also disclosed why dye
      decolorization was more electrochemically favorable during simultaneous
      bioelectricity generation and dye decolorization (SBG&DD). Quantitative
      assessment upon stimulating effects of different decolorized metabolites on BG
      and DD alone was also implemented for conclusive remarks. Apparently, using MFC
      as the method of dye decontamination could considerably increase ca. 40-70% of
      electron transfer capabilities for SBG&DD, thereby significantly improving the
      performance of dye decontamination.

PMID- 26298387
TI  - Optimisation on pretreatment of rubber seed (Hevea brasiliensis) oil via
      esterification reaction in a hydrodynamic cavitation reactor.
AB  - Pretreatment of the high free fatty acid rubber seed oil (RSO) via esterification
      reaction has been investigated by using a pilot scale hydrodynamic cavitation
      (HC) reactor. Four newly designed orifice plate geometries are studied. Cavities
      are induced by assisted double diaphragm pump in the range of 1-3.5 bar inlet
      pressure. An optimised plate with 21 holes of 1mm diameter and inlet pressure of
      3 bar resulted in RSO acid value reduction from 72.36 to 2.64 mg KOH/g within 30
      min of reaction time. Reaction parameters have been optimised by using response
      surface methodology and found as methanol to oil ratio of 6:1, catalyst
      concentration of 8 wt%, reaction time of 30 min and reaction temperature of 55
      degrees C. The reaction time and esterified efficiency of HC was three fold
      shorter and four fold higher than mechanical stirring. This makes the HC process
      more environmental friendly.

PMID- 26298388
TI  - Parkinsonism Hyperpyrexia Syndrome following Deep Brain Stimulation.

PMID- 26298389
TI  - Molecular imaging and neural networks in impulse control disorders in Parkinson's
      disease.
AB  - Impulse control disorders (ICDs) may arise in Parkinson's disease (PD) in
      relation to the use of dopamine agonists (DA). A dysfunction of reward circuits
      is considered the main underlying mechanism. Neuroimaging has been largely used
      in this setting to understand the structure of the reward system and its
      abnormalities brought by exogenous stimulation in PD. Dopaminergic changes, such
      as increased dopamine release, reduced dopamine transporter activity and other
      changes, have been shown to be a consistent feature of ICDs in PD. Beyond the
      striatum, alterations of prefrontal cortical function may also impact an
      individuals' propensity for impulsivity. Neuroimaging is advancing our knowledge
      of the mechanisms involved in the development of these behavioral addictions. An
      increased understanding of these disorders may lead to the discovery of new
      therapeutic targets, or the identification of risk factors for the development of
      these disorders. 

PMID- 26298390
TI  - Invasion of ovarian cancer cells is induced byPITX2-mediated activation of TGF
      beta and Activin-A.
AB  - BACKGROUND: Most ovarian cancers are highly invasive in nature and the high
      burden of metastatic disease make them a leading cause of mortality among all
      gynaecological malignancies. The homeodomain transcription factor, PITX2 is
      associated with cancer in different tissues. Our previous studies demonstrated
      increased PITX2 expression in human ovarian tumours. Growing evidence linking
      activation of TGF-beta pathway by homeodomain proteins prompted us to look for
      the possible involvement of this signalling pathway in PITX2-mediated progression
      of ovarian cancer. METHODS: The status of TGF-beta signalling in human ovarian
      tissues was assessed by immunohistochemistry. The expression level of TGFB/INHBA
      and other invasion-associated genes was measured by quantitative-PCR (Q-PCR) and
      Western Blot after transfection/treatments with clones/reagents in normal/cancer
      cells. The physiological effect of PITX2 on invasion/motility was checked by
      matrigel invasion and wound healing assay. The PITX2- and activin-induced
      epithelial-mesenchymal transition (EMT) was evaluated by Q-PCR of respective
      markers and confocal/phase-contrast imaging of cells. RESULTS: Human ovarian
      tumours showed enhanced TGF-beta signalling. Our study uncovers the PITX2-induced
      expression of TGFB1/2/3 as well as INHBA genes (p < 0.01) followed by SMAD2/3
      dependent TGF-beta signalling pathway. PITX2-induced TGF-beta pathway regulated
      the expression of invasion-associated genes, SNAI1, CDH1 and MMP9 (p < 0.01) that
      accounted for enhanced motility/invasion of ovarian cancers. Snail and MMP9 acted
      as important mediators of PITX2-induced invasiveness of ovarian cancer cells.
      PITX2 over-expression resulted in loss of epithelial markers (p < 0.01) and gain
      of mesenchymal markers (p < 0.01) that contributed significantly to ovarian
      oncogenesis. PITX2-induced INHBA expression (p < 0.01) contributed to EMT in both
      normal and ovarian cancer cells. CONCLUSIONS: Overall, our findings suggest a
      significant contributory role of PITX2 in promoting invasive behaviour of ovarian
      cancer cells through up-regulation of TGFB/INHBA. We have also identified the
      previously unknown involvement of activin-A in promoting EMT. Our work provides
      novel mechanistic insights into the invasive behavior of ovarian cancer cells.
      The extension of this study have the potential for therapeutic applications in
      future.

PMID- 26298391
TI  - Long-term histological and mucin alterations in the neobladder mucosa following
      urinary bladder augmentation or substitution with gastrointestinal segment.
AB  - INTRODUCTION: Bladder augmentation is widely used to treat otherwise unmanageable
      urinary incontinence. However, it is associated with a large number of
      complications, of which tumor formation is the most severe. Mucin proteins and
      MUC genes are linked, among others, to malignancies of the urinary bladder and
      the gastrointestinal system. OBJECTIVE: To investigate histological alterations
      as well as changes in expression of MUC1 and MUC2 genes and proteins following
      different types of urinary bladder augmentation or substitution performed in
      children and adolescents. PATIENTS AND METHODS: Between 1988 and 2013, 91
      patients underwent urinary bladder augmentation or substitution at the study
      institute. Patients were included on whom cystoplasty had been performed 4 years
      previously or earlier, and could have been followed-up prospectively. Thus, 54
      patients were involved in the study. In eight patients gastrocystoplasty was
      performed, in 17 patients ileocystoplasty, and in 22 patients colocystoplasty.
      Seven patients underwent bladder substitution using a colonic-segment. Biopsies
      were taken via cystoscopy from the native bladder, from the gastrointestinal
      segment used for augmentation, and from the anastomotic line between these two.
      One part of the samples was fixed in formaldehyde for routine histological
      processing. The other part of the biopsies was embedded into OCT medium, then
      cryosectioned and fluorescently double-immunostained for MUC1 and MUC2 proteins.
      Samples from the microscopically dysplastic lesions and from the 15-year-old or
      older biopsies were processed by laser capture microdissection, and then real
      time PCR was done. Data were statistically analyzed by ANOVA and ordinary least
      squares regression tests. RESULTS: One adenocarcinoma was found in a female
      patient, 11 years after colocystoplasty. There were no significant changes in the
      level of MUC1 and MUC2 proteins and gene expression in the urothelium and in the
      gastrointestinal segment used for augmentation following ileocystoplasty and
      gastrocystoplasty. Significant increase in MUC1 and decrease in MUC2 protein
      levels were detected following colocystoplasty in the large bowel segment used
      for augmentation, both with qualitative and quantitative methods (p < 0.05)
      (Figure). The uroepithelium showed no significant change. RT-PCR revealed
      progressive increase in MUC1 gene expression and decrease in MUC2 gene expression
      after colocystoplasty in the course of time. It also showed highly increased MUC1
      gene expression and decreased MUC2 gene expression in the samples of patients.
      CONCLUSIONS: Alterations in gene expression of MUC1 and MUC2 might serve as
      promising markers for early detection of histological changes after
      colocystoplasty.

PMID- 26298392
TI  - Spectrum of digoxin-induced ocular toxicity: a case report and literature review.
AB  - BACKGROUND: Digoxin intoxication results in predominantly digestive, cardiac and
      neurological symptoms. This case is outstanding in that the intoxication occurred
      in a nonagenarian and induced severe, extensively documented visual symptoms as
      well as dysphagia and proprioceptive illusions. Moreover, it went undiagnosed for
      a whole month despite close medical follow-up, illustrating the difficulty in
      recognizing drug-induced effects in a polymorbid patient. CASE PRESENTATION:
      Digoxin 0.25 mg qd for atrial fibrillation was prescribed to a 91-year-old woman
      with an estimated creatinine clearance of 18 ml/min. Over the following 2-3 weeks
      she developed nausea, vomiting and dysphagia, snowy and blurry vision, photopsia,
      dyschromatopsia, aggravated pre-existing formed visual hallucinations and
      proprioceptive illusions. She saw her family doctor twice and visited the eye
      clinic once until, 1 month after starting digoxin, she was admitted to the
      emergency room. Intoxication was confirmed by a serum digoxin level of 5.7 ng/ml
      (reference range 0.8-2 ng/ml). After stopping digoxin, general symptoms resolved
      in a few days, but visual complaints persisted. Examination by the
      ophthalmologist revealed decreased visual acuity in both eyes, 4/10 in the right
      eye (OD) and 5/10 in the left eye (OS), decreased color vision as demonstrated by
      a score of 1/13 in both eyes (OU) on Ishihara pseudoisochromatic plates, OS
      cataract, and dry age-related macular degeneration (ARMD). Computerized static
      perimetry showed non-specific diffuse alterations suggestive of either bilateral
      retinopathy or optic neuropathy. Full-field electroretinography (ERG) disclosed
      moderate diffuse rod and cone dysfunction and multifocal ERG revealed central
      loss of function OU. Visual symptoms progressively improved over the next 2
      months, but multifocal ERG did not. The patient was finally discharged home after
      a 5 week hospital stay. CONCLUSION: This case is a reminder of a complication of
      digoxin treatment to be considered by any treating physician. If digoxin is
      prescribed in a vulnerable patient, close monitoring is mandatory. In general,
      when facing a new health problem in a polymorbid patient, it is crucial to elicit
      a complete history, with all recent drug changes and detailed complaints, and to
      include a drug adverse reaction in the differential diagnosis.

PMID- 26298393
TI  - Liver-targeted antiviral peptide nanocomplexes as potential anti-HCV
      therapeutics.
AB  - Great success in HCV therapy was achieved by the development of direct-acting
      antivirals (DAA). However, the unsolved issues such as high cost and genotype
      dependency drive us to pursue additional therapeutic agents to be used instead or
      in combination with DAA. The cationic peptide p41 is one of such candidates
      displaying submicromolar anti-HCV potency. By electrostatic coupling of p41 with
      anionic poly(amino acid)-based block copolymers, antiviral peptide nanocomplexes
      (APN) platform was developed to improve peptide stability and to reduce
      cytotoxicity associated with positive charge. Herein, we developed a facile
      method to prepare galactosylated Gal-APN and tested their feasibility as liver
      specific delivery system. In vitro, Gal-APN displayed specific internalization in
      hepatoma cell lines. Even though liver-targeted and non-targeted APN displayed
      comparable antiviral activity, Gal-APN offered prominent advantages to prevent
      HCV association with lipid droplets and suppress intracellular expression of HCV
      proteins. Moreover, in vivo preferential liver accumulation of Gal-APN was
      revealed in the biodistribution study. Altogether, this work illustrates the
      potential of Gal-APN as a novel liver-targeted therapy against HCV. 

PMID- 26298395
TI  - [Convention on the rights of persons with disabilities in mental health. A human
      rights issue].

PMID- 26298394
TI  - High-performance thin-layer chromatography for the evaluation of voacamine
      intracellular concentration related to its cytotoxic effect.
AB  - Previous investigations demonstrated that pretreatment with non-cytotoxic
      concentrations of voacamine had a chemosensitizing effect on cultured multidrug
      resistant osteosarcoma cells exposed to doxorubicin; whereas when used alone at
      high concentrations voacamine induced apoptosis-independent cell death on both
      sensitive and resistant cells. To gain insight into the mechanism of action of
      voacamine at the subcellular level, we developed an analytical high-performance
      thin-layer chromatography technique to assess the intracellular content of
      voacamine that could be correlated with the induction of cell death and
      consequent morphological and ultrastructural changes. The results of the
      quantitative analysis not only did allow us to measure both the amount of
      unmodified voacamine molecules (determined by the method) and the amount of
      molecules which reacted with cellular components (undetectable), but also to
      confirm the findings of our previous studies and support the validity of this
      method.

PMID- 26298396
TI  - Psychiatry and the new compensation scale for motor vehicle accidents.

PMID- 26298397
TI  - Comments on differences of gender dysphoria between children and teenagers.

PMID- 26298398
TI  - Turner syndrome: From birth to adulthood.
AB  - BACKGROUND: Turner syndrome is characterized by a great variability of clinical
      manifestations caused by a total or partial loss of X-chromosome. PATIENTS AND
      METHODS: A retrospective, descriptive study of the diagnosis, course, and current
      status of patients with Turner syndrome followed up at our section over the past
      40 years, based on review of medical records supplemented with a telephone
      survey. RESULTS: Forty-five female patients with a current mean age of 22.95years
      (range 2-38) and a mean age at diagnosis of 4.71 were included. Sixty-three
      percent of them showed a mosaic karyotype. Short stature was the most common
      reason for consultation (54%), with increased prenatal diagnosis in most recent
      cases. Seventy-two percent have been treated with growth hormone, together with
      oxandrolone in 26%. Final stature was short in 69% of patients. Gonadal failure
      was found in 66%; most of whom received replacement therapy. Three patients
      achieved pregnancy by oocyte donation. The 31 adult patients are mainly monitored
      by the endocrinology (37.5%) and/or gynecology (34.4%) departments. As regards
      psychosocial aspects, 22% required support during school, and 80% completed
      middle to high level education. Two patients died, one due to dissecting aortic
      aneurysm and the other one, who had multiple pathological conditions, from
      respiratory failure. CONCLUSIONS: Short stature is the main cause of diagnosis in
      patients with Turner syndrome; most cases show genetic mosaicism. The most common
      clinical manifestations include short stature and gonadal failure. Eighty percent
      of patients complete middle or high education. In adulthood, follow-up is
      irregular, sometimes scarce, and clearly improvable.

PMID- 26298400
TI  - Assessing Change Readiness and Treatment Eagerness among Psychoactive Substance
      Users in Northern Nigeria.
AB  - Studies on psychoactive substance use in Nigeria had focused on prevalence and
      rarely on treatment implication(s) of large rates reported. Further challenge was
      to find suitable instruments to monitor change readiness as well as predict
      treatment outcomes along motivation continuum and according to resilience
      characteristics. Such ability will not only help to match treatment strategy with
      stage of change but also come with a more satisfactory outcome. This study
      therefore provided psychometric properties of one of such measuring scales: Stage
      of Change Readiness and Treatment Eagerness Scale version 8 (SOCRATES-8) and the
      accompanying change in resilience among Nigerians using psychoactive substances.
      Participants were 111 psychoactive substance dependent users in three treatment
      centers in Northern Nigeria. All respondents filled sociodemographic
      questionnaire, SOCRATES-8 and 14-item Resilience Scale. The study found overall
      motivation for change among participants to be medium on the three subscales of
      SOCRATES-8: ambivalence (median=14.00; range=7-20); recognition (median=31.00;
      range=7-35); and taking steps (median=35.00; range=12-40). More than half (61.3%)
      scored moderately on resilience. The Internal reliability of SOCRATES-8's
      subscales fell into acceptable range (ambivalence=0.54; recognition=0.87; taking
      steps=0.84). Pearson correlation coefficients of subscales with resilience are
      positive and in moderate range except for ambivalence with very low coefficient.
      Hierarchical cluster analysis based on participants' resilience characteristics
      yields five distinct profiles corresponding to five stages of motivational
      change. ANOVA of these five profiles based on SOCRATES' 3 subscales was
      significant. The study demonstrates utility of SOCRATES-8 to assess change
      readiness and treatment eagerness of psychoactive substance abusers according to
      stages of change and their resilience characteristics. This will aid treatment
      planning and can also measure treatment outcome. 

PMID- 26298399
TI  - Engagement and Substance Dependence in a Primary Care-Based Addiction Treatment
      Program for People Infected with HIV and People at High-Risk for HIV Infection.
AB  - To improve outcomes for people with substance dependence and HIV infection or at
      risk for HIV infection, patients were enrolled in a primary care-based addiction
      treatment program from 2008-2012 that included a comprehensive substance use
      assessment, individual and group counseling, addiction pharmacotherapy and case
      management. We examined whether predisposing characteristics (depression, housing
      status, polysubstance use) and an enabling resource (buprenorphine treatment)
      were associated with engagement in the program and persistent substance
      dependence at 6 months. At program enrollment 61% were HIV-infected, 53% reported
      heroin use, 46% reported alcohol use, 37% reported cocaine use, and 28% reported
      marijuana use in the past 30 days, 72% reported depression, 19% were homeless,
      and 53% had polysubstance use. Within 6-months 60% had been treated with
      buprenorphine. Engagement (defined as 2 visits in first 14 days and 2 additional
      visits in next 30 days) occurred in 64%; 49% had substance dependence at 6
      months. Receipt of buprenorphine treatment was associated with engagement
      (Adjusted Odds Ratio (AOR) 8.32 95% CI: 4.13-16.77). Self-reported depression at
      baseline was associated with substance dependence at 6-months (AOR 3.30 95% CI:
      1.65-6.61). Neither housing status nor polysubstance use was associated with
      engagement or substance dependence. The FAST PATH program successfully engaged
      and treated patients in a primary care-based addiction treatment program.
      Buprenorphine, a partial opioid agonist, was a major driver of addiction
      treatment engagement. Given depression's association with adverse outcomes in
      this clinical population, including mental health treatment as part of integrated
      care holds potential to improve addiction treatment outcomes. 

PMID- 26298401
TI  - A study on the use of the BioBall(r) as a biofilm carrier in a sequencing batch
      reactor.
AB  - Described in this study are experiments conducted to evaluate the removal of
      organics and nutrients from synthetic wastewater by a moving bed sequencing batch
      biofilm reactor using BioBall(r) carriers as biofilm media. The work involving a
      15L-laboratory scale MBSBBR (moving bed sequencing batch biofilm reactor) model
      showed that the wastewater treatment system was based on biochemical processes
      taking place with activated sludge and biofilm microorganisms developing on the
      surface of the BioBall(r) carriers. Classical nitrification and denitrification
      and the typical enhanced biological phosphorus removal process were achieved in
      the reactor analyzed, which operated with a volumetric organic loading of 0.84
      0.978gCODL(-1)d(-1). The average removal efficiencies for COD, total nitrogen and
      total phosphorus were found to be 97.7+/-0.5%, 87.8+/-2.6% and 94.3+/-1.3%,
      respectively. Nitrification efficiency reached levels in the range 96.5-99.7%.

PMID- 26298402
TI  - Structure and distribution of inorganic components in the cake layer of a
      membrane bioreactor treating municipal wastewater.
AB  - A laboratory-scale submerged anoxic-oxic membrane bioreactor treating municipal
      wastewater was operated to investigate the structure and distribution of the
      inorganic cake layer buildup on the membrane. BCR (European Community Bureau of
      Reference) sequential extraction, X-ray photoelectron spectroscopy (XPS), and
      both map and line scan of energy-dispersive X-ray analysis (EDX) were performed
      for cake layer characterization. BCR results showed that Si, Al, Ca, Mg, Fe, and
      Ba were the predominant inorganic elements in the cake layer, and they occurred
      mostly as crystal particles. Crystal SiO2 was the dominant inorganic compound
      while Ca in the form of CaSO4 (dominant) and CaCO3 were also present, but exerted
      little effect on the cake layer structure because most of these compounds were
      deposited as precipitates on the reactor bottom. EDX results indicated that Si
      and Al accumulated together along the cross-sectional cake layer in the form of
      Si-Al (SiO2-Al2O3) crystal particles.

PMID- 26298403
TI  - Improved docosahexaenoic acid production in Aurantiochytrium by glucose limited
      pH-auxostat fed-batch cultivation.
AB  - Fed-batch, pH auxostat cultivation of the docosahexaenoic acid (DHA)-producing
      microorganism Aurantiochytrium B072 was performed to obtain high cell density and
      record high productivity of both total fatty acid (TFA) and DHA. Using glucose
      feeding by carbon excess (C-excess) and by C-limitation at various feeding rates
      (70%, 50% or 20% of C-excess), high biomass density was obtained and DHA/TFA
      content (w/w) was improved from 30% to 37% with a 50% glucose feed rate when
      compared with C-excess. To understand the biochemistry behind these improvements,
      lipogenic enzyme assays and in silico metabolic flux calculations were used and
      revealed that enzyme activity and C-fluxes to TFA were reduced with C-limited
      feeding but that the carbon flux to the polyketide synthase pathway increased
      relative to the fatty acid synthase pathway. As a result, a new strategy to
      improve the DHA to TFA content while maintaining relatively high DHA productivity
      is proposed.

PMID- 26298404
TI  - Biocatalytic methanation of hydrogen and carbon dioxide in a fixed bed
      bioreactor.
AB  - Biocatalytic methanation of H2 and CO2 was studied in a fixed bed reactor system
      consisting of two solid state bioreactors in series connected to a recirculation
      system. Bioreactors were packed with a mixture of vermiculite shales and granular
      perlite material as a support material. A maximal methane productivity of
      6.35l/lreactord was achieved at a hydrogen feed rate of 25.2l/lreactord, while
      hydrogen conversion rate was 100%. However, stable operation of the reactor at
      this efficiency remains to be achieved. Very simple reactor design, constructed
      from low cost materials, and the idea of exploiting waste material as a robust
      source of nutrients for methanogens makes this study very interesting regarding
      the overall usability and suitability of the system as part of a decentralized
      energy system.

PMID- 26298405
TI  - Comparing activated carbon of different particle sizes on enhancing methane
      generation in upflow anaerobic digester.
AB  - Two sizes of conductive particles, i.e. 10-20 mesh granulated activated carbon
      (GAC) and 80-100 mesh powdered activated carbon (PAC) were added into lab-scale
      upflow anaerobic sludge blanket reactors, respectively, to testify their
      enhancement on the syntrophic metabolism of alcohols and volatile fatty acids
      (VFAs) in 95days operation. When OLR increased to more than 5.8gCOD/L/d, the
      differences between GAC/PAC supplemented reactors and the control reactor became
      more significant. The introduction of activated carbon could facilitate the
      enrichment of methanogens and accelerate the startup of methanogenesis, as
      indicated by enhanced methane yield and substrate degradation. High-throughput
      pyrosequencing analysis showed that syntrophic bacteria and Methanosarcina sp.
      with versatile metabolic capability increased in the tightly absorbed fraction on
      the PAC surface, leading to the promoted syntrophic associations. Thus PAC
      prevails over than GAC for methanogenic reactor with heavy load.

PMID- 26298406
TI  - Feasibility of bioethanol production from tubers of Dioscorea sansibarensis and
      Pyrenacantha kaurabassana.
AB  - Inedible tubers from Dioscorea sansibarensis (DS) and Pyrenacantha kaurabassana
      (PK) were found to be suitable feedstock for bioethanol production. Important
      composition parameters for bioethanol production for DS and PK are dry matter (%
      fresh tubers) ca. 20 and 6, total carbohydrates % dry weight base (db) ca. 68 and
      47 and total protein (% db) ca. 16 and 10, respectively. DS and PK were found to
      contain inulin and galactomannan as principal polysaccharides (% of total
      carbohydrate) ca. 90 and 70, respectively. Diluted acid hydrolysis yielded ca.
      100% of total reducing sugars. Ethanol yield ca. 56 and 35g/L was obtained at
      high efficiency through batch fermentation of acid hydrolysate (25% w/v) of DS
      and PK, respectively. A simple technique of recording and monitoring ethanol
      through CO2 generated during fermentation correlated strongly with HPLC
      measurement R(2)=0.99. Thus, tubers from these plants are potential feedstocks
      for bioethanol production with no competing uses.

PMID- 26298407
TI  - Risk-stratification protocol for carboplatin and oxaliplatin hypersensitivity:
      repeat skin testing to identify drug allergy.
AB  - BACKGROUND: Hypersensitivity reactions (HSRs) to platinum-based chemotherapies
      are increasingly being recognized. The authors developed a novel risk
      stratification protocol that was used successfully in a small number of patients
      with carboplatin-induced HSRs. OBJECTIVE: To describe the utility of this
      protocol in a large number of patients with carboplatin- or oxaliplatin-induced
      HSRs. METHODS: A 5-year retrospective review of patients referred to
      Massachusetts General Hospital with carboplatin- or oxaliplatin-induced HSR was
      performed. Patients were managed using a risk-stratification protocol using 3
      repeat skin tests (STs) with intervening desensitizations. If the repeat ST
      result remained negative 3 times, patients received subsequent infusions without
      desensitization. RESULTS: From 2008 to 2012, 142 patients (92 treated with
      carboplatin, 50 treated with oxaliplatin) completed 574 desensitizations. Most
      patients were women (84.5%, mean +/- SD 58.1 +/- 9.3 years). Patients with
      carboplatin-induced HSRs were classified as having positive (n = 32, 34.8%),
      negative (n = 38, 41.3%), or converted (n = 22, 23.9%) ST reactions when the
      initial negative ST reaction converted to positive at repeat ST. Of those with
      oxaliplatin-induced HSRs, 22 (44%) had positive, 25 (50%) had negative, and 3
      (6%) had converted ST reactions. Of the patients with negative ST reactions, 17
      with carboplatin-induced HSRs and 16 with oxaliplatin-induced HSRs safely
      completed 59 and 95 outpatient infusions, respectively, without desensitizations.
      For carboplatin and oxaliplatin, ST conversion was associated with an interval of
      at least 6 months from the HSR to the initial ST (carboplatin, P = .002;
      oxaliplatin, P = .045). CONCLUSION: This risk-stratification protocol for
      presumed carboplatin- and oxaliplatin-induced HSRs safely identifies false
      negative ST reactions and nonallergic patients who can receive infusions without
      desensitizations. This leads to fewer unnecessary desensitizations and improved
      patient care.

PMID- 26298408
TI  - The BOC ELISA, a ruminant-specific AMH immunoassay, improves the determination of
      plasma AMH concentration and its correlation with embryo production in cattle.
AB  - Plasma anti-Mullerian hormone (AMH) concentrations have been recently found to be
      predictive of the number of embryos recovered after FSH superovulatory treatment
      in the cow. However, the sensitivity of the Active Mullerian-inhibiting
      substance/AMH ELISA (ref. 10-14400; DSL-Beckman-Coulter) used to make these
      measurements in bovine plasma samples is low because it was developed to measure
      human AMH levels. To overcome this limitation, we developed an immunoassay
      specific for the bovine (B), ovine (O), and caprine (C) species, the bovine-ovine
      caprine (BOC) ELISA. For this purpose, we produced recombinant bovine AMH for
      standardization, and we used monoclonal antibodies raised against bovine AMH,
      previously prepared by our laboratory. We evaluated the precision, accuracy,
      specificity, limit of detection, and functional sensitivity of the assay. The
      intra-assay coefficient of variation ranged between 3.4% and 11.3% for AMH
      concentrations between 23.68 and 1.74 ng/mL, and the interassay coefficient of
      variation ranged between 4.8% and 20.5% for concentrations between 25.53 and 1.42
      ng/mL, respectively. The assay displayed a good linearity, had a detection limit
      of 0.4 ng/mL and a functional sensitivity of 1.4 ng/mL. It also cross-reacted
      with ovine and caprine AMHs. Both the mean and median AMH levels measured in 40
      cow plasma samples using the BOC ELISA were approximately 44 fold higher than the
      mean and median AMH levels measured with the Active Mullerian-inhibiting
      substance/AMH ELISA. Moreover, a higher correlation was observed between the
      average number of embryos recovered from each cow after superovulatory treatment
      and AMH concentrations measured with the BOC ELISA. This BOC ELISA provides a
      very efficient tool for evaluating the ovarian follicular reserve of cows and
      predicting their embryo production capacity. 

PMID- 26298409
TI  - A new framework for selecting environmental surrogates.
AB  - Surrogate concepts are used in all sub-disciplines of environmental science.
      However, controversy remains regarding the extent to which surrogates are useful
      for resolving environmental problems. Here, we argue that conflicts about the
      utility of surrogates (and the related concepts of indicators and proxies) often
      reflect context-specific differences in trade-offs between measurement accuracy
      and practical constraints. By examining different approaches for selecting and
      applying surrogates, we identify five trade-offs that correspond to key points of
      contention in the application of surrogates. We then present an 8-step Adaptive
      Surrogacy Framework that incorporates cross-disciplinary perspectives from a wide
      spectrum of the environmental sciences, aiming to unify surrogate concepts across
      disciplines and applications. Our synthesis of the science of surrogates is
      intended as a first step towards fully leveraging knowledge accumulated across
      disciplines, thus consolidating lessons learned so that they may be accessible to
      all those operating in different fields, yet facing similar hurdles. 

PMID- 26298410
TI  - Stimulus-induced reflex epileptic spasms in 5p- syndrome.
AB  - Here we describe two patients with 5p- syndrome who suffered from epilepsy
      characterised by stimulus-induced epileptic spasms manifesting as head nodding.
      In patient 1, a series of spasms were exclusively triggered by eating, and were
      associated with diffuse high-voltage slow waves on ictal EEG, particularly
      presenting as a positive slow potential at the left mid-temporal area. Clusters
      of sharp waves with negative polarity emerged in the same area during the inter
      spasm periods during eating. In patient 2, spasms were provoked by either eating
      or micturition. Ictal EEG of clustered spasms after micturition showed positive
      slow or triphasic waves, which correlated with each spasm, over the bifrontal and
      vertex areas. These findings suggest that the focal cortical areas act as trigger
      regions in reflex epilepsies, and that a spasm-generator responsible for the
      execution of reflex spasms exists either in other cortical areas or in the
      subcortical structures. Although epilepsy is an unusual complication of 5p-
      syndrome, this syndrome may have a propensity to develop reflex epilepsy,
      particularly epileptic spasms. However, identification of responsible genes and
      their roles in this phenotype requires further investigations. 

PMID- 26298411
TI  - This is London calling: a few recollections on the path to the 2015 ESC congress.

PMID- 26298412
TI  - Paravalvular aortic regurgitation after TAVI: new insight.

PMID- 26298413
TI  - CAD in TAVI patients: relevance of disease complexity.

PMID- 26298414
TI  - Periprocedural oral anticoagulation during percutaneous coronary interventions:
      more evidence to fuel an uninterrupted debate.

PMID- 26298415
TI  - Renal sympathetic nerve denervation using intraluminal ultrasound within a
      cooling balloon preserves the arterial wall and reduces sympathetic nerve
      activity.
AB  - AIMS: Circumferential ablation of renal sympathetic nerves using catheter-based
      ultrasound energy was studied in a preclinical in vivo model. The aim was to
      investigate the benefit of cooling the arterial wall and the extent of renal
      nerve injury based on histopathology, and to correlate the injury with kidney
      norepinephrine levels. METHODS AND RESULTS: Computer simulations of the
      ultrasound transducer within the cooling balloon demonstrated a circumferentially
      uniform heating profile. In vivo characterisation was performed in 10
      normotensive pigs. Nine were treated bilaterally with ultrasound and survived for
      seven days (n=8) or were sacrificed acutely (n=1). Acutely, TTC staining of the
      renal arteries treated with ultrasound energy in the presence of cooling
      demonstrated viable tissue consistent with preservation of the arterial medial
      layer. Histological studies demonstrated no endothelial injury and minimal to no
      injury to the media of the renal arterial wall at seven days. Overall,
      circumferential nerve damage with up to 76% of nerve bundles affected within 7.5
      mm of the arterial lumen was observed. Kidney norepinephrine (NEPI) levels were
      significantly reduced in all animals compared to a non-treated control animal
      (n=1) and correlated with the degree of nerve damage. A greater reduction in NEPI
      and a greater percentage of affected nerves was observed in arteries treated with
      two or three bilateral ultrasound emissions. CONCLUSIONS: Catheter-based
      ultrasound delivered within a cooling balloon is effective at targeting the
      majority of the renal nerves circumferentially, resulting in significantly
      decreased kidney NEPI levels without damaging the arterial wall in a porcine
      model.

PMID- 26298416
TI  - Background frequency of Bacillus species at the Canberra Airport: A 12 month
      study.
AB  - Anthrax, caused by Bacillus anthracis, is a naturally occurring disease in
      Australia. Whilst mainly limited to livestock in grazing regions of Victoria and
      New South Wales, movement of people, stock and vehicles means B. anthracis could
      be present outside this region. Of particular interest is the "background"
      prevalence of B. anthracis at transport hubs including airports. The aim of this
      study was to determine the background frequency of B. anthracis and the commonly
      used hoax agent Bacillus thuringiensis at the Canberra Airport over a 12 month
      period. Samples were collected daily for seven days each month from August 2011
      July 2012 and analyzed using species specific real-time polymerase chain
      reaction. Fourteen samples (of a total of 575) were positive for the B. anthracis
      PL3 genomic marker, 24 for the cya (pXO1) plasmid marker and five for the capB
      (pXO2) plasmid marker. Whilst five samples were positive for both PL3 and cya, no
      samples were positive for all three markers hence there is no evidence to suggest
      the presence of pathogenic B. anthracis strains. B. anthracis targets were
      detected primarily in February 2012 and B. thuringiensis peaked in October and
      November 2011 and again in April and May 2012. This study provides a rapid method
      to screen for, and differentiate, Bacillus species. Armed with this information
      investigators will be able to discriminate a "threat" from "background"
      frequencies should the need arise. 

PMID- 26298417
TI  - Performance of computer-based analysis using temporal subtraction to assess joint
      space narrowing progression in rheumatoid patients.
AB  - Our computer-based method can detect the chronological change in joint space
      width between baseline and follow-up images as the joint space difference index
      (JSDI). The aim of this study was to verify the sensitivity and specificity of
      our computer-based method in assessment of joint space narrowing progression in
      rheumatoid patients. Twenty-seven patients (24 women and 3 men) with rheumatoid
      arthritis underwent radiography of the bilateral hand at baseline and at 1 year.
      The joint space narrowing (JSN) of a total of 252 metacarpophalangeal (MCP)
      joints and 229 carpal joints was assessed by our computer-based method, setting
      the Sharp/van der Heijde method as the gold standard. We constructed a receiver
      operating characteristic curve by using the Sharp/van der Heijde method as the
      gold standard and set the optimal cutoff on JSDI for MCP, carpal, and MCP/carpal
      joints. We then calculated the sensitivity and specificity for each cutoff in
      assessment of JSN progression. At the most discriminant cutoff, the sensitivity
      and specificity of the computer-based method for MCP joints was 78.6 versus 85.3
      %, respectively (AUC = 0.837; P < 0.001). Carpal joints revealed a lower
      sensitivity and specificity with 64.7 and 86.8 % (AUC = 0.775; P < 0.001).
      Furthermore, the sensitivity and specificity for MCP/carpal joints was 71.0
      versus 83.6 %, respectively (AUC = 0.778; P < 0.001). The computer-based method
      presented a reliable assessment of JSN progression with high sensitivity and
      specificity and may be useful in follow-up assessment of the joint damage in
      rheumatoid patients.

PMID- 26298418
TI  - CD47 on artificial structures.

PMID- 26298419
TI  - Body ownership and response to threat.
AB  - A virtual-reality setup was used to investigate the relationship between
      perceived body ownership and subjective anxiety, as assessed by an anxiety
      inventory (SA-I). A pilot study confirmed that synchrony between the
      participant's real hand movements and the movements of a virtual effector induced
      perceived ownership illusions. The illusions were comparable for virtual human
      hands and virtual cat claws, even though the overall acceptance was greater for
      human hands. In Experiment 1, participants used the virtual effector to collect
      coins and avoid knives descending on a screen before anxiety was measured. The
      level of anxiety increased with synchrony and was higher for human hands than for
      cat claws, but these two effects were independent. Experiment 2 separated effects
      of coin catching and knife avoiding by means of a between-participant design. The
      outcome of Experiment 1 was replicated in the knife-avoiding task but not in the
      coin-catching task, in which anxiety levels were low and not systematically
      affected by the type of virtual effector. Taken altogether, our findings suggest
      that subjective anxiety and ownership are strongly related.

PMID- 26298420
TI  - Computed tomography and (18)F-fluorodeoxyglucose positron emission
      tomography/computed tomography findings in adrenal candidiasis and
      histoplasmosis: two cases.
AB  - We report the contrast-enhanced computed tomography (CT) and (18)F
      fluorodeoxyglucose positron emission tomography findings in adrenal
      histoplasmosis and candidiasis. Both demonstrated bilateral hypermetabolic
      heterogeneous adrenal masses with limited wash-out on delayed CT. Adrenal
      candidiasis has not been previously reported, nor have the CT wash-out findings
      in either infection. The adrenal imaging findings are indistinguishable from
      malignancy, which is more common; but in this setting, physicians should be alert
      to the differential diagnosis of fungal infections, since it can be equally
      deadly. 

PMID- 26298421
TI  - The role of virtual colonoscopy in colorectal screening.
AB  - Colorectal cancer is the second leading cause of cancer-related deaths in the
      United States. The earlier colorectal cancer is detected, the better chance a
      person has of surviving 5 years after being diagnosed, emphasizing the need for
      effective and regular colorectal screening. Computed tomographic colonography has
      repeatedly demonstrated sensitivities equivalent to the current gold standard,
      optical colonoscopy, in the detection of clinically relevant polyps. It is an
      accurate, safe, affordable, available, reproducible, quick, and cost-effective
      option for colorectal screening and should be considered for mass screening. 

PMID- 26298422
TI  - The development of the illusion of control and sense of agency in 7- to-12-year
      old children and adults.
AB  - The illusion of control can be defined as the erroneous belief that one's actions
      cause a specific outcome, whereas sense of agency refers to the subjective
      feeling of authorship over one's actions. In the present study we investigated
      the development of illusory control and sense of agency. A novel card-guessing
      game was developed in which 7- to-12-year old children (Study 1) and adults
      (Study 2) were required to select a card, and we manipulated the congruence of
      the outcome with their initial choice (i.e., congruent or incongruent) and the
      valence of the outcome that was presented (i.e., positive or negative). We found
      that illusory control and the self-attribution bias (i.e., the bias to attribute
      positive outcomes to oneself) in the card guessing game decreased, as children
      get older. In contrast, for both children and adults sense of agency in the task
      was similarly affected by outcome congruency, suggesting that the ability to
      relate predicted to observed action outcomes reflects a basic mechanism that
      helps people to sustain a sense of agency. Thus, while the illusion of control
      decreases as we get older, the experience of agency as a function of outcome
      congruency seems to be more stable across development.

PMID- 26298423
TI  - Adopting the ritual stance: The role of opacity and context in ritual and
      everyday actions.
AB  - Rituals are a pervasive and ubiquitous aspect of human culture, but when we
      naively observe an opaque set of ritual actions, how do we come to understand its
      significance? To investigate this, across two experiments we manipulated the
      degree to which actions were ritualistic or ordinary, and whether or not they
      were accompanied with context. In Experiment 1, 474 adult participants were
      presented with videos of novel rituals (causally opaque actions) or control
      actions (causally transparent) performed on a set of objects accompanied with
      neutral-valance written context. Experiment 2 presented the same video stimuli
      but with negative and aversive written context. In both experiments ritualized
      objects were rated as physically unchanged, but more 'special' and more
      'desirable' than objects subjected to control actions, with context amplifying
      this effect. Results are discussed with reference to the Ritual Stance and the
      Social-Action hypothesis. Implications for both theories are discussed, as are
      methodological concerns regarding the empirical investigation of ritual
      cognition. We argue that causally opaque ritual actions guide the behavior of
      naive viewers because such actions are perceived as socially normative, rather
      than with reference to supernatural intervention or causation. 

PMID- 26298424
TI  - Unifying morality's influence on non-moral judgments: The relevance of
      alternative possibilities.
AB  - Past work has demonstrated that people's moral judgments can influence their
      judgments in a number of domains that might seem to involve straightforward
      matters of fact, including judgments about freedom, causation, the doing/allowing
      distinction, and intentional action. The present studies explore whether the
      effect of morality in these four domains can be explained by changes in the
      relevance of alternative possibilities. More precisely, we propose that moral
      judgment influences the degree to which people regard certain alternative
      possibilities as relevant, which in turn impacts intuitions about freedom,
      causation, doing/allowing, and intentional action. Employing the stimuli used in
      previous research, Studies 1a, 2a, 3a, and 4a show that the relevance of
      alternatives is influenced by moral judgments and mediates the impact of morality
      on non-moral judgments. Studies 1b, 2b, 3b, and 4b then provide direct empirical
      evidence for the link between the relevance of alternatives and judgments in
      these four domains by manipulating (rather than measuring) the relevance of
      alternative possibilities. Lastly, Study 5 demonstrates that the critical
      mechanism is not whether alternative possibilities are considered, but whether
      they are regarded as relevant. These studies support a unified framework for
      understanding the impact of morality across these very different kinds of
      judgments. 

PMID- 26298427
TI  - Trends of barriers to eye care among adults with diagnosed diabetes in Germany,
      1997-2012.
AB  - BACKGROUND AND AIMS: To study trends of barriers to receiving recommended eye
      care among subjects with diabetes aged 20-81 years in northeast Germany. METHODS
      AND RESULTS: We analyzed population-based data from two repeated cross-sectional
      surveys conducted in 1997-2001 and 2008-2012 (Ns of 4308 and 4402). Andersen's
      Behavioral Model of Health Services Utilization was used to identify individual
      level demographic, financial and health-related barriers to annual eye-care
      utilization in subjects with a self-reported physician's diabetes and to examine
      population trends in these barriers. The prevalence of diabetes increased from
      6.5% to 11.4%. The prevalence of annual eye-care utilization among persons with
      diabetes decreased from 69.4% to 56.0% (adjusted relative risk = 0.77, p <
      0.001). The decline of eye care utilization over the past decade in eye-care use
      was more pronounced in groups at risk for diabetes-related complications (i.e.,
      lower socio-economic status, >5 years since diagnosis of diabetes, poor glycemic
      control, obesity, smoking, lack of physical activity, co-existing diseases). We
      identified relevant predictors of missed annual eye-care use among diabetics.
      CONCLUSION: The increase of diabetes prevalence and downward trend of eye-care
      visits at the recommended level call for development, implementation and
      evaluation of continued efforts to improve access to eye specialists,
      particularly among those with poor diabetic control, co-existing diabetic
      complications, and comorbidities.

PMID- 26298426
TI  - Mild hyponatremia, hypernatremia and incident cardiovascular disease and
      mortality in older men: A population-based cohort study.
AB  - AIM: To examine the association between serum sodium concentration and incident
      major cardiovascular disease (CVD) outcomes and total mortality in older men.
      METHODS AND RESULTS: A prospective study of 3099 men aged 60-79 years without a
      history of cardiovascular disease followed up for an average 11 years during
      which there were 528 major CVD events (fatal coronary heart disease [CHD] and non
      fatal MI, stroke and CVD death) and 873 total deaths. A U shaped relationship was
      seen between serum sodium concentration and major CVD events and mortality.
      Hyponatremia (<136 mEq/L) and low sodium within the normal range (136-138 mEq/L)
      showed significantly increased risk of major CVD events and total mortality
      compared to men within the upper normal range (139-143 mEq/L) after adjustment
      for a wide range of confounders and traditional risk factors [adjusted HRs 1.55
      (1.13,2.12) and 1.40 (1.14,1.72) for major CVD events respectively and 1.30
      (1.02,1.66) and 1.30 (1.11,1.53) respectively for total mortality]. Hyponatremia
      was associated with inflammation, NT-proBNP, low muscle mass and alkaline
      phosphatase; these factors contributed to the increased total mortality
      associated with hyponatremia but did not explain the increased risk of CVD events
      associated with hyponatremia or low normal sodium concentration. Hypernatremia
      (>=145 mEq/L) was associated with significantly increased risk of CVD events and
      mortality due to CVD causes. CONCLUSION: Mild hyponatremia even within the normal
      sodium range and hypernatremia are both associated with increased total mortality
      and major CVD events in older men without CVD which is not explained by known
      adverse CV risk factors.

PMID- 26298425
TI  - A multicenter observational study on the management of hyperglycemia in patients
      with acute coronary syndrome.
AB  - AIM: To assess the prevalence, risk and management of hyperglycemia in patients
      with acute coronary syndrome (ACS). METHODS AND RESULTS:  DESIGN: a multicenter
      prospective observational study of a representative sample of patients with ACS
      consecutively admitted to intensive cardiac care units (ICCU). SETTING: 31 out of
      61 ICCUs in Lombardy, the most heavily populated Italian region. From May 2009 to
      April 2010 1260 patients (69.4% male; mean age 68 +/- 13 years) were included in
      the study: 301 (23.9%) were known diabetic patients (D) and 265 (21.0%) had
      hyperglycemia (H) (blood glucose >180 mg/dL) at hospital admission, 174 with a
      history of diabetes (D+H+) and 91 without (D-H+). On the first day after
      admission intravenous insulin infusion was prescribed to 72 D+H+ (41.4%) and 10 D
      H+ (11.0%), according to different protocols. Approximately one third of D+H+
      patients (59) and one fifth (17) of D-H+ maintained mean blood glucose higher
      than 180 mg/dL during the first day in the ICCU. Patients with diabetes or
      hyperglycemia had a higher incidence of major adverse cardiovascular events or
      death in hospital. However, at multivariable analysis neither diabetes nor blood
      glucose at admission was associated with a poor prognosis whereas mean blood
      glucose on the first day was an independent negative prognostic predictor (OR
      1.010, 95% CI 1.002-1.018, p = 0.016). CONCLUSION: Hyperglycemia is frequent in
      patients with ACS and is independently associated with a poor in-hospital
      prognosis if it persists in first day. Unfortunately, however, this condition is
      still poorly treated, with far from optimal blood glucose control.

PMID- 26298428
TI  - Intake of polyunsaturated fat in relation to mortality among statin users and non
      users in the Southern Community Cohort Study.
AB  - BACKGROUND AND AIMS: Consumption of polyunsaturated fatty acids (PUFA),
      especially the n3-series, may protect against cardiovascular disease (CVD), but
      recent randomized studies have failed to demonstrate these benefits. One of the
      prevailing hypotheses is that PUFA intake may not confer benefits beyond those
      provided by statins, but studies comparing statin users to non-users with regard
      to effects of PUFA are lacking. METHODS AND RESULTS: Black and white men and
      women (n = 69,559) in the Southern Community Cohort Study were studied. Cox
      regression models adjusting for age, sex, race, BMI, recruitment site, education,
      income, smoking, diabetes, and dietary variables were used. RESULTS: At baseline
      the mean +/- SD age was 52 +/- 9 years, 60% of participants were women, 54% had
      hypertension and 16% used statins. We observed modest inverse associations
      between n3-PUFA and n6-PUFA intake with mortality among non-statin users but not
      among statin users. In adjusted analyses, the HRs (95% CIs) for all-cause
      mortality (6,396 deaths over a median of 6.4 years) comparing the highest to the
      lowest quintile were 0.90 (0.82-1.00) for n3-PUFA and 0.80 (0.70-0.92) for n6
      PUFA among non-statin users, whereas they were 1.06 (0.87-1.28) and 0.96 (0.78
      1.19) for n3-PUFA and n6-PUFA, respectively, among statin users. CONCLUSIONS: Our
      results suggest potential benefits of PUFA consumption on mortality which are
      only apparent in the absence of statin therapy. It seems prudent to consider the
      potential benefit of PUFA consumption in the primary prevention of CVD among
      patients who are not candidates for statin therapy but are at increased risk for
      CVD and mortality.

PMID- 26298429
TI  - Low protein and micronutrient intakes in heterogeneous older population samples.
AB  - BACKGROUND: Malnutrition is associated with comorbidities and functional decline
      among older people. Less is known about nutrient intakes across heterogeneous
      older populations. OBJECTIVE: We examined nutritional status and nutrient intakes
      in different samples of older people representing broad spectrum of healthy and
      frail populations. We evaluated adequacy of their energy, protein and
      micronutrient intakes in comparison to recommendations. DESIGN AND PARTICIPANTS:
      Cross-sectional study combined five datasets: home-dwelling older people
      participating in nutrition education and cooking classes (NC) [n=54],
      participants from Helsinki Businessmen Study [n=68], home-dwelling people with
      Alzheimer disease (AD) [n=99] and their spousal caregivers (n=97), participants
      from Porvoo Sarcopenia and Nutrition Trial (n=208), and residents of Helsinki
      assisted living facilities (ALF) [n=374]. Nutritional status was assessed using
      Mini Nutritional Assessment and nutrient intakes retrieved from 1 to 3 day food
      records. RESULTS: Those suffering most from mobility limitation and cognitive
      decline had the poorest nutritional status (p<0.001; adjusted for age, sex,
      comorbidities). However, low intakes of energy, protein, and micronutrients were
      observed in high proportion in all groups, inadequate intakes of vitamins D, E,
      folate, and thiamine being most common. Protein intakes did not differ between
      the groups, but 77% of all participants had lower than recommended protein
      intake. In general, the NC group had highest micronutrient intakes and the ALF
      group the lowest. However, AD females had the lowest energy, protein, and vitamin
      C intakes. CONCLUSIONS: Our study provides a detailed picture of risks related to
      nutrient intakes in various groups of older people. These findings could be used
      in planning tailored nutrition interventions.

PMID- 26298432
TI  - Targeting of non-oncogene addiction.

PMID- 26298430
TI  - Regulatory T cells, inherited variation, and clinical outcome in epithelial
      ovarian cancer.
AB  - The immune system constitutes one of the host factors modifying outcomes in
      ovarian cancer. Regulatory T cells (Tregs) are believed to be a major factor in
      preventing the immune response from destroying ovarian cancers. Understanding
      mechanisms that regulate Tregs in the tumor microenvironment could lead to the
      identification of novel targets aimed at reducing their influence. In this study,
      we used immunofluorescence-based microscopy to enumerate Tregs, total CD4 T
      cells, and CD8(+) cytotoxic T cells in fresh frozen tumors from over 400 patients
      with ovarian cancer (>80 % high-grade serous). We sought to determine whether
      Tregs were associated with survival and genetic variation in 79 genes known to
      influence Treg induction, trafficking, or function. We used Cox regression,
      accounting for known prognostic factors, to estimate hazard ratios (HRs)
      associated with T cell counts and ratios. We found that the ratios of CD8 T cells
      and total CD4 T cells to Tregs were associated with improved overall survival
      (CD8/Treg HR 0.84, p = 0.0089; CD4/Treg HR 0.88, p = 0.046) and with genetic
      variation in IL-10 (p = 0.0073 and 0.01, respectively). In multivariate analyses,
      the associations between the ratios and overall survival remained similar (IL-10
      and clinical covariate-adjusted CD8/Treg HR 0.85, p = 0.031; CD4/Treg HR 0.87, p
      = 0.093), suggesting that this association was not driven by variation in IL-10.
      Thus, integration of novel tumor phenotyping measures with extensive clinical and
      genetic information suggests that the ratio of T cells to Tregs may be prognostic
      of outcome in ovarian cancer, regardless of inherited genotype in genes related
      to Tregs.

PMID- 26298433
TI  - Children's use of interventions to learn causal structure.
AB  - Children between 5 and 8 years of age freely intervened on a three-variable
      causal system, with their task being to discover whether it was a common cause
      structure or one of two causal chains. From 6 or 7 years of age, children were
      able to use information from their interventions to correctly disambiguate the
      structure of a causal chain. We used a Bayesian model to examine children's
      interventions on the system; this showed that with development children became
      more efficient in producing the interventions needed to disambiguate the causal
      structure and that the quality of interventions, as measured by their
      informativeness, improved developmentally. The latter measure was a significant
      predictor of children's correct inferences about the causal structure. A second
      experiment showed that levels of performance were not reduced in a task where
      children did not select and carry out interventions themselves, indicating no
      advantage for self-directed learning. However, children's performance was not
      related to intervention quality in these circumstances, suggesting that children
      learn in a different way when they carry out interventions themselves.

PMID- 26298434
TI  - A study of gamma-ray and neutron radiation in the interaction of a 2 MeV proton
      beam with various materials.
AB  - Epithermal neutron source based on a tandem accelerator with vacuum insulation
      and lithium target has been proposed, developed and operated in Budker Institute
      of Nuclear Physics. The source is regarded as a prototype of a future compact
      device suitable for carrying out BNCT in oncology centers. In this work the
      measurements of gamma-ray and neutron radiation are presented for the interaction
      of a 2 MeV proton beam with various materials (Li, C, F, Al, V, Ti, Cu, Mo,
      stainless steel, and Ta). The obtained results enabled the optimization of the
      neutron-generating target and the high energy beam transportation path.

PMID- 26298435
TI  - Investigation on the reflector/moderator geometry and its effect on the neutron
      beam design in BNCT.
AB  - In order to provide an appropriate neutron beam for Boron Neutron Capture Therapy
      (BNCT), a special Beam Shaping Assembly (BSA) must be designed based on the
      neutron source specifications. A typical BSA includes moderator, reflector,
      collimator, thermal neutron filter, and gamma filter. In common BSA, the
      reflector is considered as a layer which covers the sides of the moderator
      materials. In this paper, new reflector/moderator geometries including multi
      layer and hexagonal lattice have been suggested and the effect of them has been
      investigated by MCNP4C Monte Carlo code. It was found that the proposed
      configurations have a significant effect to improve the thermal to epithermal
      neutron flux ratio which is an important neutron beam parameter. 

PMID- 26298436
TI  - Biodistribution of boron after intravenous 4-dihydroxyborylphenylalanine-fructose
      (BPA-F) infusion in meningioma and schwannoma patients: A feasibility study for
      boron neutron capture therapy.
AB  - We studied the uptake of boron after 100 mg/kg BPA infusion in three meningioma
      and five schwannoma patients as a pre-BNCT feasibility study. With average tumour
      to-whole blood boron concentrations of 2.5, we discuss why BNCT could, and
      probably should, be developed to treat severe forms of the studied tumours.
      However, analysing 72 tumour and 250 blood samples yielded another finding: the
      plasma-to-whole blood boron concentrations varied with time, suggesting that the
      assumed constant boron ratio of 1:1 between normal brain tissue and whole blood
      deserves re-assessment.

PMID- 26298437
TI  - Wound healing complications in brain tumor patients on Bevacizumab.
AB  - Bevacizumab (BEV) is commonly used for treating recurrent glioblastoma (GBM), and
      wound healing is a well-established adverse event. Retrospective analysis of GBM
      patients with and without wound healing complications while on BEV treatment is
      reported. 287 patients identified, majority were males (60 %) with median age of
      52.5 years. 14 cases identified with wound healing problems, related to either
      craniotomy (n = 8) or other soft tissue wounds (n = 6). Median duration of BEV
      treatment to complication was 62 days (range 6-559). Majority received 10 mg/kg
      (n = 11) and nine (64.3 %) were on corticosteroids, with median daily dose of 6
      mg (range 1-16 mg) for median of 473 days before starting BEV. For dehisced
      craniotomy wounds, median time for starting BEV from last surgery was 29 days
      (range 27-345). Median time from starting BEV to developing wound complication
      was 47 days (range 16-173). Seven (87.5 %) had infected wounds requiring
      antibiotics, hospitalization. Four (50 %) required plastic surgery. BEV stopped
      and safely resumed in 6 (75 %) patients; median delay was 70 days (range 34-346).
      Soft tissue wounds included decubitus ulcer, dehisced striae, herpes simplex,
      trauma to hand and back, and abscess. Median time from starting BEV to wound
      issues was 72 days (range 6-559). Five (83.3 %) were infected, requiring
      antibiotics. While three (50 %) required hospitalization, none required plastic
      surgery. Treatment stopped in five (83.3 %) and restarted in two (median delay 48
      days, range 26-69). Wound healing complications are uncommon but associated with
      significant morbidity. Identifying those at risk and contributing factors
      warrants further investigation. 

PMID- 26298438
TI  - A systematic review of the health effects of prenatal exposure to disaster.
AB  - OBJECTIVES: The aim of this study was to determine the health effects of prenatal
      exposure to disaster, based on a systematic review of existing research. METHODS:
      A literature search of scientific databases was conducted in February 2015 for
      articles on prenatal exposure to a natural or man-made disaster. Data was
      extracted from all articles that met the inclusion criteria, and we
      systematically analyzed contents based on type of disaster, health outcome,
      target group and time after birth. RESULTS: Prenatal exposure to famine or war
      was found to be associated with mental health, cardiovascular or metabolic
      outcomes, with varying degrees of significance. The majority of the studies
      showed limited or weak associations between exposures and outcomes. CONCLUSIONS:
      Due to the lack of variety in type of events studied, as well as large
      methodological variation, it is difficult to draw firm conclusions from existing
      literature. However, our systematic review highlights the potential of evaluating
      secondary data, both to accentuate research gaps in the field and to increase the
      understanding of what effects various types of disasters potentially have on the
      unborn child.

PMID- 26298439
TI  - Hepatitis C in key populations in Latin America and the Caribbean: systematic
      review and meta-analysis.
AB  - OBJECTIVES: Summarize hepatitis C virus (HCV) prevalence in injecting (IDU) and
      non-injecting drug users (NIDU), men who have sex with men (MSM), sex workers,
      and prison inmates in Latin America and the Caribbean (LAC). METHODS: Systematic
      review on HCV prevalence in sub-populations in LAC. Databases searched from 1-1
      2000 to 10-30-2013. INCLUSION CRITERIA: prevalence studies in sub-populations in
      LAC. HCV-antibody was marker for prevalence of current/past HCV infection and HCV
      RNA for prevalence of HCV current infection. RESULTS: IDU HCV current/past
      infection presented highest prevalence, from 1.7 % in Colombia to over 95 % in
      Ciudad Juarez and Tijuana, Mexico and pooled regional anti-HCV prevalence was 49
      % (CI 95 % 22.6-76.3 %). NIDU, MSM and sex workers anti-HCV prevalence was below
      10 %, and pooled regional prevalence of 4 % (CI 95 % 2.6-4.5 %), 3 % (CI 95 % 1.7
      4.5 %) and 2 % (CI 95 % 1.0-3.4 %), respectively. Prison inmates presented higher
      values, but prevalence decreased over the 15-year time span (p < 0.001). Current
      HCV infection from three countries showed prevalence under 10 % in prison inmates
      and 1-46 % among drug users. CONCLUSIONS: Disease burden is high and
      surveillance, prevention and treatment should target these groups in LAC.

PMID- 26298440
TI  - Socioeconomic position during childhood and physical activity during adulthood: a
      systematic review.
AB  - OBJECTIVES: A growing body of evidence links socioeconomic position early in life
      and physical activity during adulthood. This systematic review aimed to summarize
      this evidence. METHODS: Medline and EMBASE were searched for studies that
      assessed socioeconomic position before age 18 years and physical activity at age
      >=18 years. Studies were rated according to three key methodological quality
      criteria: (1) was childhood socioeconomic position assessed prospectively? (2)
      Was socioeconomic position during adulthood included in the statistical analysis?
      (3) Was a validated instrument used to measure of physical activity? RESULTS:
      Forty-two publications were included. Twenty-six (61.9 %) found a significant
      association between socioeconomic position early in life and physical activity
      during adulthood. Twenty-one studies met at least two methodological quality
      criteria. Among those, the proportion was higher: 15/21 (71.4 %). Associations
      were of weak to moderate strength, positive for physical activity during leisure
      time, and negative for transports and work. CONCLUSIONS: The bulk of the evidence
      supports the notion that there is a life course association between socioeconomic
      position early in life and physical activity during adulthood. Studies using more
      rigorous methodology supported this conclusion more consistently.

PMID- 26298441
TI  - Equity in maternal health care service utilization: a systematic review for
      developing countries.
AB  - OBJECTIVES: The objective was to explore progress of equity in the utilization of
      maternal health care services in developing countries since maternal care is a
      crucial factor in reducing maternal mortality, which is targeted by the
      Millennium Development Goal 5. METHODS: A systematic review of quantitative
      studies was done. PubMed Central, Web of Science, and Science Direct databases
      were searched for peer-reviewed and English-language articles published between
      2005 and 2015. RESULTS: Thirty-six articles were included in the review. The
      results reveal the lack of equity in the utilization of maternal health care in
      developing countries. Thirty-three out of 36 studies found evidence supporting
      severe inequities while three studies found evidence of equity or at least
      improvement in terms of equity. CONCLUSIONS: Most of the literature devoted to
      utilization of maternal health care generally provides information on the level
      of maternal care used and ignore the equity problem. Research in this area should
      focus not only on the level of maternal care used but also on the most
      disadvantaged segments of the population in terms of utilization of maternal care
      in order to reach the set targets.

PMID- 26298442
TI  - The mental health impact of bed bug infestations: a scoping review.
AB  - OBJECTIVES: We conducted a scoping review to identify and summarize the current
      state of knowledge regarding the mental health effects associated with bed bugs.
      METHODS: We employed a five-stage scoping review framework, to systematically
      identify and review eligible articles. Eligibility criteria included a focus on
      bed bug infestations and reference to mental health impacts. Descriptive
      information was then extracted from each article, including the specific mental
      health effects cited. RESULTS: An initial search yielded 920 unique articles on
      the topic of bed bugs. Of these, 261 underwent abstract review, and 167 underwent
      full-text review. Full-text review and subsequent review of reference lists
      yielded a final sample of 51 articles. Numerous mental health effects were linked
      to bed bug infestations, including severe psychiatric symptoms. However, the
      majority (n = 31) of the articles were commentary papers; only five original
      research articles were identified. CONCLUSIONS: Although significant mental
      health effects are often linked to bed bugs, such discussions remain largely
      anecdotal. Despite recognition that the impact of bed bugs constitutes an
      important public health concern, little empirical evidence currently exists on
      this topic.

PMID- 26298444
TI  - Exposing concerns about vaccination in low- and middle-income countries: a
      systematic review.
AB  - OBJECTIVES: Concerns about vaccination lead to under- and no-vaccination. Our
      objective is to synthesise and expose evidence on individuals' and communities'
      concerns about vaccination to influence current debates on strategies to improve
      vaccination coverage in low- and middle-income countries. METHODS: Systematic
      literature review till February 2014, following standard methods. Published and
      grey literature that focused on individuals and community concerns on childhood
      vaccinations were selected. RESULTS: 44 quantitative, qualitative and mixed
      methods studies were included. Main reported concerns referred to perceptions of
      vaccine harms (e.g. attribution of fatal events). Other concerns included
      programme distrust (mainly due to rumours and conspiracies) and health system
      unfriendliness. CONCLUSIONS: Concerns about vaccination are widespread and
      further worsen the challenges related to programmatic and health system barriers
      to vaccination. There is a disconnection between qualitative and quantitative
      research which misses the opportunity to quantify what is reported in the former.
      Strikingly, there is a wealth of evidence on concerns but much lesser evidence on
      interventions to address them. We welcome World Health Organization initiative to
      tackle vaccine hesitancy and call for the synthesis of evidence and production of
      guidance on strategies to address concerns on vaccination.

PMID- 26298443
TI  - Considering treatment of male genital schistosomiasis as a tool for future HIV
      prevention: a systematic review.
AB  - OBJECTIVES: Male genital schistosomiasis (MGS) is a neglected manifestation of
      Schistosoma haematobium infection with ignored implications on reproductive
      health and a differential diagnosis to sexually transmitted infections in endemic
      regions. MGS may have associations with HIV transmission and acquisition, and
      treatment could be a neglected chance of HIV prevention. This review summarizes
      current knowledge on epidemiology, clinical manifestations, diagnosis and
      treatment of MGS as a hypothesized risk factor for HIV transmission. Future
      research areas of global interest are suggested. METHODS: PubMed published
      literature was reviewed based on the MOOSE guidelines. All publications on MGS
      were included regardless of publication year and study design. Furthermore, all
      publications were searched for information on possible HIV association. RESULTS:
      The 40 identified publications related to MGS were dominated by case reports and
      observational studies. No randomized clinical trials have been conducted to date,
      and very scant information related to possible associations with HIV transmission
      was presented. CONCLUSIONS: Clinical, randomized studies and epidemiological
      studies covering the possible association between MGS and HIV are urgently
      needed. Furthermore, field diagnostic tools should be developed and future mass
      treatment programs should include adults to reduce morbidity and prevent HIV
      acquisition. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42015016252.

PMID- 26298445
TI  - What research tells us about knowledge transfer strategies to improve public
      health in low-income countries: a scoping review.
AB  - OBJECTIVES: This study describes the current state of research on knowledge
      transfer strategies to improve public health in low-income countries, to identify
      the knowledge gaps on this topic. METHODS: In this scoping review, a descriptive
      and systematic process was used to analyse, for each article retained,
      descriptions of research context and methods, types of knowledge transfer
      activities and results reported. RESULTS: 28 articles were analysed. They dealt
      with the evaluation of transfer strategies that employed multiple activities,
      mostly targeting health professionals and women with very young children. Most
      often these studies used quantitative designs and measurements of instrumental
      use with some methodological shortcomings. Results were positive and suggested
      recommendations for improving professional practices, knowledge and health
      related behaviours. The review highlights the great diversity of transfer
      strategies used, strategies and many conditions for knowledge use. CONCLUSIONS:
      The review provides specific elements for understanding the transfer processes in
      low-income countries and highlights the need for systematic evaluation of the
      conditions for research results utilization.

PMID- 26298446
TI  - A systematic literature review of the quality of evidence for injury and
      rehabilitation interventions in humanitarian crises.
AB  - INTRODUCTION: Humanitarian crises continue to pose a significant threat to
      health; the United Nations estimates that 144 million people are directly
      affected by conflict or environmental disasters. During most humanitarian crises,
      surgical and rehabilitative interventions remain a priority. OBJECTIVES: This
      review assessed the quality of evidence that informs injury and physical
      rehabilitation interventions in humanitarian crises. METHODS: Peer-reviewed and
      grey literature sources were assessed in a systematic manner. Selected papers
      were evaluated using quality criteria based on a modified version of the STROBE
      protocol. RESULTS: 46 papers met the inclusion criteria. 63 % of the papers
      referred to situations of armed conflict, of which the Yugoslav Wars were the
      most studied crisis context. 59 % of the studies were published since the year
      2000. However, only two studies were considered of a high quality. CONCLUSIONS:
      While there is now a greater emphasis on research in this sector, the volume of
      evidence remains inadequate given the growing number of humanitarian programmes
      worldwide. Further research is needed to ensure a greater breadth and depth of
      understanding of the most appropriate interventions in different settings.

PMID- 26298447
TI  - Atrial Fibrillation: Would You Prefer a Pill or 150 Joules?

PMID- 26298448
TI  - An Observational Study of the Factor Xa Inhibitors Rivaroxaban and Apixaban as
      Reported to Eight Poison Centers.
AB  - STUDY OBJECTIVE: Rivaroxaban and apixaban are part of a new group of oral
      anticoagulants targeting factor Xa and approved by the Food and Drug
      Administration in 2011 and 2012. These oral anticoagulants are administered at
      fixed daily doses, without the need for laboratory-guided adjustments. There are
      limited data available on supratherapeutic doses or overdose of the oral Xa
      inhibitors. This study characterizes the clinical effect in patients exposed to
      rivaroxaban and apixaban. METHODS: A retrospective study collected data from 8
      regional poison centers covering 9 states. Cases were initially identified by a
      search of the poison centers' databases for case mentions involving a human
      exposure to Xarelto, rivaroxaban, Eliquis, or apixaban. Inclusion criteria
      included single-substance exposure. Exclusion criteria were animal exposure,
      polysubstance exposure, or information call. Data for the study were collected by
      individual chart review, including case narratives, and compiled into a single
      data set. RESULTS: There were 223 patients: 124 (56%) were female patients, mean
      age was 60 years, and 20 were children younger than 12 years (9%). One hundred
      ninety-eight patients ingested rivaroxaban (89%) and 25 ingested apixaban (11%).
      Dose was reported in 182 rivaroxaban patients, with a mean dose of 64.5 mg (range
      15 to 1,200 mg), and in 21 apixaban patients, with a mean dose of 9.6 mg (range
      2.5 to 20 mg). For rivaroxaban, prothrombin time was measured in 49 patients
      (25%) and elevated in 7; partial thromboplastin time, measured in 49 (25%) and
      elevated in 5; and international normalized ratio, measured in 61 (31%) and
      elevated in 13. For apixaban, prothrombin time was measured in 6 patients (24%)
      and elevated in none; partial thromboplastin time, measure in 6 (24%) and
      elevated in none; and international normalized ratio, measured in 5 patients
      (20%) and elevated in none. Bleeding was reported in 15 patients (7%): 11
      rivaroxaban and 4 apixaban. The site of bleeding was gastrointestinal (8), oral
      (2), nose (1), bruising (1), urine (1), and subdural (1). The subdural bleeding
      occurred after fall and head injury. All cases with bleeding involved long-term
      ingestions. Coagulation test results were normal in most patients with bleeding:
      prothrombin time 5 of 6 (83%), partial thromboplastin time 5 of 6 (83%), and
      international normalized ratio 5 of 9 (55%). Blood products were used in 7
      rivaroxaban patients (1 suicide) and 3 apixaban patients. No bleeding or altered
      coagulation test results occurred in children, which all involved a one-time
      ingestion. All 12 suicide attempts involved rivaroxaban: altered coagulation test
      results occurred for 5 patients (42%), no bleeding occurred in any suicide
      attempt patient, 1 patient was treated with fresh frozen plasma (international
      normalized ratio 12.47), and dose by patient history did not predict risk of
      altered coagulation or bleeding. Two rivaroxaban patients experienced elevation
      of hepatic transaminase levels greater than 1,000 U/L. CONCLUSION: Bleeding after
      Xa inhibitor ingestion as a single agent is uncommon. Prothrombin time, partial
      thromboplastin time, or international normalized ratio may be elevated in a
      minority of cases but appears unreliable to measure risk of bleeding. Massive
      acute ingestion in suicide attempt may result in significant anticoagulation.
      Single exploratory ingestion by children was not associated with toxicity.

PMID- 26298449
TI  - From Context Comes Expertise: How Do Expert Emergency Physicians Use Their Know
      Who to Make Decisions?
AB  - STUDY OBJECTIVE: Decisionmaking is influenced by the environment in which it
      takes place. The objective of our study was to explore the influence of the
      specific features of the emergency department (ED) environment on decisionmaking.
      In this paper, we specifically report on the way emergency physicians use their
      knowledge of their collaborators to make their decisions. METHODS: We conducted a
      qualitative study on emergency physicians recruited in 3 French hospitals.
      Physicians were equipped with a microcamera to record their clinical activity
      from their "own-point-of-view perspective." Semistructured interviews, based on
      viewing the video, were held with each physician after an actual clinical
      encounter with a patient. They were then analyzed thematically, using constant
      comparison and matrices, to identify the central themes. RESULTS: Fifteen expert
      emergency physicians were interviewed. Almost all of them reported using their
      knowledge of other health care professionals to assess the seriousness of the
      patient's overall condition (sometimes even before his or her arrival in the ED)
      to optimize the patient's treatment and to anticipate future care. CONCLUSION:
      Emergency physicians interact with many other health care workers during the
      different stages of the patient's management. The many ways in which experts use
      their knowledge of other health care professionals to make decisions puts
      traditional conceptions of expert knowledge into perspective and opens avenues
      for future research.

PMID- 26298450
TI  - Chylous ascites secondary to cirrhosis of the liver: A case report.

PMID- 26298451
TI  - Exploring the conformational space of bridge-substituted dithienylcyclopentenes.
AB  - Stimuli responsive compounds and materials are of high interest in synthetic
      chemistry and materials science, with light being the most intriguing stimulus
      due to the possibility to remote control the physicochemical properties of a
      molecule or a material. There is a constant quest to design photoswitches with
      improved switching efficiency and especially diarylethene-type switches promise
      photo cyclization quantum yields up to unity. However, only limited attention has
      been paid towards the influence of the solution conformation on the switching
      efficiency. Here, we describe a detailed NMR spectroscopic investigation on the
      conformational distribution of bridge-substituted dithienylcyclopentenes in
      solution. We could discriminate between several photoactive and photoinactive as
      well as two diastereomorphous conformations and show that the trends observed in
      the switching efficiency match the conformer populations obtained from state of
      the art NMR parameters in solution. 

PMID- 26298452
TI  - Caesarean section per se does not increase the risk of offspring developing type
      1 diabetes: a Swedish population-based study.
AB  - AIMS/HYPOTHESIS: Some studies have revealed a relationship between Caesarean
      section (CS) and type 1 diabetes, while other studies have not. By using the
      Swedish paediatric quality register we investigated whether birth by CS is
      related to the risk of developing type 1 diabetes during childhood. METHODS: All
      children diagnosed with type 1 diabetes from 2000 to 2012 and included in the
      register (n = 9,376) were matched with four controls by year, day of birth, sex
      and county of birth from the Swedish Medical Birth Register. RESULTS: Overall,
      13.5% of deliveries were by CS. By group, 14.7% of children who developed type 1
      diabetes were delivered by CS compared with 13.3% of control children (p <
      0.001). Mothers with diabetes more often gave birth by CS than mothers without
      diabetes (78.8% vs 12.7%, p < 0.001). In a logistic regression model adjusting
      for maternal age, maternal diabetes and BMI in early pregnancy, the OR for CS was
      1.0. A child who developed type 1 diabetes and had a mother with type 1 diabetes
      at the time of delivery had the highest OR to have been born by CS. Children of
      mothers without diabetes, delivered by CS, had no increased risk of developing
      type 1 diabetes. Maternal diabetes was the strongest predictor of childhood
      diabetes (OR 3.4), especially if the mother had type 1 diabetes (OR 7.54).
      CONCLUSIONS/INTERPRETATION: CS had no influence on the risk of type 1 diabetes
      during childhood or adolescence. However, maternal diabetes itself strongly
      increased the risk of offspring developing type 1 diabetes.

PMID- 26298454
TI  - How Phytochemicals Prevent Chemical Carcinogens and/or Suppress Tumor Growth?
AB  - Phytochemicals are a powerful group of chemicals that are derived from natural
      resource, especially with plants origin. They have shown to exhibit
      chemoprevention and chemotherapeutic effects not only in cell lines and in animal
      models of cancer but also some of them are in the clinical trial phase I and II.
      Despite numerous reports of these phytochemical effects on cancer, an overview of
      the mechanisms of their action and their effects on various cellular and
      molecular functions important in the inhibition of cancer progression has been
      lacking. In this review, we attempt to catalogue various studies to examine the
      effect of phytochemicals in cancer initiation, promotion, signaling, and
      epigenetic changes. Because of the numerous studies in these topics, we only
      pointed out to some examples in each section. 

PMID- 26298453
TI  - Peripheral neurolymphomatosis with tracheal asphyxia: a case report and
      literature review.
AB  - BACKGROUND: Neurolymphomatosis (NL) is an extremely rare disease and tracheal
      asphyxia due to NL has not been previously reported. CASE PRESENTATION: A 54-year
      old Chinese woman with a history of diffuse large B-cell lymphoma in her first
      complete remission developed peripheral neuropathy and tracheal asphyxia.
      Neurolymphomatosis involving the right brachial plexus and the right vagus nerve
      was demonstrated by PET/CT, but not by MRI. She underwent urgent tracheotomy and
      impact chemotherapy using rituximab combined with high dose methotrexate and
      involved field radiotherapy. She achieved a second complete remission.
      CONCLUSION: PET/CT plays valuable role in differentiating NL from other
      neuropathies in patients with lymphoma. Complete remission can be achieved in NL
      due to large B-cell lymphoma.

PMID- 26298455
TI  - Quercetin and Tryptanthrin: Two Broad Spectrum Anticancer Agents for Future
      Chemotherapeutic Interventions.
AB  - The idea and practice of developing or identifying compounds capable of
      eliminating the transformed cells or cancer cells without being nontoxic to their
      normal counterparts deserves much importance. Since ages, plants have been
      considered and proven to be repertoires of chemicals possessing immense
      therapeutic potential. A proportion of these plant-derived compounds or
      phytochemicals were shown to be highly competent anticancer agents besides being
      effective against many other diseases. Representative compounds of different
      classes of phytochemicals are in clinical use against cancer. In this chapter, we
      discuss the anticancer potential of two compounds: quercetin, a flavonoid and
      tryptanthrin, an indoloquinazoline alkaloid, and the mechanisms behind their
      cytotoxic effects on cancers of different origin. The chapter also gives a brief
      mention of their properties that make them effective against cancer. 

PMID- 26298456
TI  - Potential Anticancer Properties and Mechanisms of Action of Withanolides.
AB  - Plant-based Ayurvedic medicine has been practiced in India for thousands of years
      for the treatment of a variety of disorders. They are rich sources of bioactive
      compounds potentially useful for prevention and treatment of cancer. Withania
      somnifera (commonly known as Ashwagandha in Ayurvedic medicine) is a widely used
      medicinal plant whose anticancer value was recognized after isolation of
      steroidal compounds withanolides from the leaves of this shrub. Withaferin A is
      the first member of withanolides to be isolated, and it is the most abundant
      withanolide present in W. somnifera. Its cancer-protective role has now been
      established using chemically induced and oncogene-driven rodent cancer models.
      The present review summarizes the key preclinical studies demonstrating
      anticancer effects of withaferin along with its molecular targets and mechanisms
      related to its anticancer effects. Anticancer potential of other withanolides is
      also discussed. 

PMID- 26298457
TI  - Prenylated Dihydrochalcones from Artocarpus altilis as Antiausterity Agents.
AB  - Human pancreatic cancer cell lines have remarkable tolerance to nutrition
      starvation, which enables them to survive under a tumor microenvironment. A novel
      antiausterity strategy in anticancer drug discovery led to the discovery of
      agents that preferentially inhibit the survival of cancer cells under low
      nutrient conditions. Artocarpus altilis (Family: Moraceae) is commonly referred
      to as breadfruit, traditionally for the treatment of many diseases. Many
      prenylated flavonoid and prenylated chalocones together with their cancer cell
      cytotoxicity were reported from this plant. This chapter briefly summarizes the
      constituents, biosynthesis, cytotoxicity, and antiausterity activity on PANC-1
      human pancreatic cancer cell line of A. altilis. 

PMID- 26298458
TI  - Mechanisms of the Anticancer Effects of Isothiocyanates.
AB  - Cancer results from aberrant signaling pathways that result in uncontrolled
      cellular proliferation. The epidemiological studies have shown a strong inverse
      correlation between dietary consumption of cruciferous vegetables and incidences
      of cancer. Isothiocyanates (ITCs) are present in cruciferous vegetables like
      broccoli, cabbage, watercress, etc. and are identified as the major active
      constituents. Several mechanistic studies have demonstrated chemopreventive and
      chemotherapeutic activity of ITCs against various tumor types. ITCs exert
      anticancer activity by suppressing various critical hallmarks of cancer like
      cellular proliferation, angiogenesis, apoptosis, metastasis, etc., in vitro as
      well as in preclinical animal model. ITCs also generate reactive oxygen species
      to induce apoptosis in cancer cells. Due to promising preclinical results, few
      ITCs have also advanced to clinical trials. This chapter provides a candid review
      on the chemopreventive and chemotherapeutic activity of various major ITCs. 

PMID- 26298459
TI  - Mechanism of the Anticancer Effect of Lycopene (Tetraterpenoids).
AB  - Increasing evidence suggests that lycopene, a major carotenoid detected in human
      plasma, may be preventive against the formation and the development of different
      types of human cancers including prostate, breast, and lung cancer. Experimental
      studies demonstrated that lycopene inhibits the growth of various cancer cells of
      different organs and prevent chemically induced carcinogenesis in animal models.
      Although the excellent antioxidant property of lycopene is most likely the basis
      for its preventive role toward cancer, the direct anticancer activities of
      lycopene through multiple mechanisms are disclosed, including regulation of
      growth factor signaling, cell cycle arrest and/or apoptosis induction, and
      changes in antioxidant and phase II detoxifying enzymes. The anti-inflammatory
      activity of lycopene is also considered as an important determinant that
      suppresses the promotion and progression of carcinogenesis. Moreover, lycopene
      inhibits cell invasion, angiogenesis, and metastasis. Importantly, those
      activities have been shown to be exhibited at the physiologically attainable
      concentration in humans. Although the preclinical data strongly suggest an
      antitumor activity of lycopene, a number of epidemiological and intervention
      studies indicate that there is still no clear clinical evidence that supports its
      use for the prevention of those cancers. More well controlled clinical
      intervention trials are needed to further clarify the exact role of lycopene in
      the cancer prevention. Nonetheless, because of its multiple tumor-inhibitory
      activities, lycopene still remains to be an attractive and promising carotenoid
      that will potentially contribute to the prevention and treatment of human
      cancers. This chapter reviews data on the cancer preventive activities of
      lycopene, possible mechanisms involved, and the relationship between lycopene
      consumption and human cancer risk. 

PMID- 26298460
TI  - Anticancer Mechanism of Sulfur-Containing Compounds.
AB  - Fruit and vegetables have traditionally represented a main source for the
      discovery of many biologically active substances with therapeutic values. Among
      the many bioactive compounds identified over the years, sulfur-containing
      compounds, which are present especially in the genera Allium and Brassica, have
      been showing a protective effect against different types of cancer. Many in vitro
      and in vivo studies reported that apoptosis is crucial for the anticancer effects
      of sulfur-containing compounds. Garlic and onion compounds and isothiocyanates
      contained in Brassica vegetables are able to modulate apoptosis by a wide range
      of mechanisms. This chapter will give an overview on the induction of apoptosis
      by sulfur-containing compounds in cancer cells and their different molecular
      mechanisms. Finally, the potential clinical implications of their proapoptotic
      effects will be discussed. 

PMID- 26298461
TI  - The Role of Soy Phytoestrogens on Genetic and Epigenetic Mechanisms of Prostate
      Cancer.
AB  - Soy phytoestrogens are dietary components with considerable effects on reducing
      the incidence of prostate cancer. Epidemiological studies demonstrated that
      occurrence of prostate cancer is relatively low in Asia and Southern Europe, a
      status associated with consuming of soy isoflavones, such as genistein, daidzein,
      and glycitein. Soy phytoestrogens exert their activity on molecular mechanisms,
      including cell-cycle control, induction of apoptosis, inhibition of angiogenesis,
      and metastasis. In addition, they have antioxidant activity and show regulatory
      effect on the expression of genes involved in DNA damage and repair. Furthermore,
      the epigenetic regulation of gene expression can be modified by soy
      phytoestrogens. They show regulatory effects on gene activity by altering DNA
      methylation and/or histone modification patterns. In this chapter, we discuss the
      role of soy phytoestrogens on the genetic and epigenetic mechanisms of prostate
      cancer. We attempt to provide further insight in order to understand the
      underlying mechanisms of protective effects of soy phytoestrogens in preventing
      prostate cancer. 

PMID- 26298462
TI  - Preface.

PMID- 26298463
TI  - Cardiometabolic Disease Leading to Heart Failure: Better Fat and Fit Than Lean
      and Lazy.
AB  - High body mass index (BMI) and low cardiorespiratory fitness (CRF) are important
      modifiable risk factors for heart failure (HF). While the individual
      contributions of CRF and BMI toward risk for HF are well established, the
      interrelationship between BMI and CRF in modifying long-term HF risk is more
      complex and not well understood. In this review, we discuss and summarize the
      available evidence-base on individual and joint contributions of obesity and low
      CRF toward HF risk, including the potential mechanisms through which these
      lifestyle risk factors may lead to HF. We also discuss the role of interventions
      aimed at intentional loss of weight or CRF improvement as potential HF preventive
      strategies. Finally, the article also highlights the modifying effects of CRF on
      survival in relation to the obesity paradox in patients with established HF. 

PMID- 26298465
TI  - Venlafaxine for neuropathic pain in adults.
AB  - BACKGROUND: Neuropathic pain, which is caused by nerve damage, is increasing in
      prevalence worldwide. This may reflect improved diagnosis, or it may be due to
      increased incidence of diabetes-associated neuropathy, linked to increasing
      levels of obesity. Other types of neuropathic pain include post-herpetic
      neuralgia, trigeminal neuralgia, and neuralgia caused by chemotherapy.
      Antidepressant drugs are sometimes used to treat neuropathic pain; however, their
      analgesic efficacy is unclear. A previous Cochrane review that included all
      antidepressants for neuropathic pain is being replaced by new reviews of
      individual drugs examining chronic neuropathic pain in the first instance.
      Venlafaxine is a reasonably well-tolerated antidepressant and is a serotonin
      reuptake inhibitor and weak noradrenaline reuptake inhibitor. Although not
      licensed for the treatment of chronic or neuropathic pain in most countries, it
      is sometimes used for this indication. OBJECTIVES: To assess the analgesic
      efficacy of, and the adverse effects associated with the clinical use of,
      venlafaxine for chronic neuropathic pain in adults. SEARCH METHODS: We searched
      the Cochrane Central Register of Controlled Trials (CENTRAL) via The Cochrane
      Library, and MEDLINE and EMBASE via Ovid up to 14 August 2014. We reviewed the
      bibliographies of any randomised trials identified and review articles, contacted
      authors of one excluded study and searched www.clinicaltrials.gov to identify
      additional published or unpublished data. We also searched the meta-Register of
      controlled trials (mRCT) (www.controlled-trials.com/mrct) and the WHO
      International Clinical Trials Registry Platform (ICTRP)
      (apps.who.int/trialsearch/) for ongoing trials but did not find any relevant
      trials. SELECTION CRITERIA: We included randomised, double-blind studies of at
      least two weeks' duration comparing venlafaxine with either placebo or another
      active treatment in chronic neuropathic pain in adults. All participants were
      aged 18 years or over and all included studies had at least 10 participants per
      treatment arm. We only included studies with full journal publication. DATA
      COLLECTION AND ANALYSIS: Three review authors independently extracted data using
      a standard form and assessed study quality. We intend to analyse data in three
      tiers of evidence as described by Hearn 2014, but did not find any first-tier
      evidence (ie evidence meeting current best standards, with minimal risk of bias)
      or second-tier evidence, that was considered at some risk of bias but with
      adequate participant numbers (at least 200 in the comparison). Third-tier
      evidence is that arising from studies with small numbers of participants; studies
      of short duration, studies that are likely to be of limited clinical utility due
      to other limitations, including selection bias and attrition bias; or a
      combination of these. MAIN RESULTS: We found six randomised, double-blind trials
      of at least two weeks' duration eligible for inclusion. These trials included 460
      participants with neuropathic pain, with most participants having painful
      diabetic neuropathy. Four studies were of cross-over design and two were parallel
      trials. Only one trial was both parallel design and placebo-controlled. Mean age
      of participants ranged from 48 to 59 years. In three studies (Forssell 2004, Jia
      2006 and Tasmuth 2002), only mean data were reported. Comparators included
      placebo, imipramine, and carbamazepine and duration of treatment ranged from two
      to eight weeks. The risk of bias was considerable overall in the review,
      especially due to the small size of most studies and due to attrition bias. Four
      of the six studies reported some positive benefit for venlafaxine. In the largest
      study by Rowbotham, 2004, 56% of participants receiving venlafaxine 150 to 225 mg
      achieved at least a 50% reduction in pain intensity versus 34% of participants in
      the placebo group and the number needed to treat for an additional beneficial
      outcome was 4.5. However, this study was subject to significant selection bias.
      Known adverse effects of venlafaxine, including somnolence, dizziness, and mild
      gastrointestinal problems, were reported in all studies but were not particularly
      problematic and, overall, adverse effects were equally prominent in placebo or
      other active comparator groups. AUTHORS' CONCLUSIONS: We found little compelling
      evidence to support the use of venlafaxine in neuropathic pain. While there was
      some third-tier evidence of benefit, this arose from studies that had
      methodological limitations and considerable risk of bias. Placebo effects were
      notably strong in several studies. Given that effective drug treatments for
      neuropathic pain are in current use, there is no evidence to revise prescribing
      guidelines to promote the use of venlafaxine in neuropathic pain. Although
      venlafaxine was generally reasonably well tolerated, there was some evidence that
      it can precipitate fatigue, somnolence, nausea, and dizziness in a minority of
      people.

PMID- 26298464
TI  - Persistent Organic Pollutant Determination in Killer Whale Scat Samples:
      Optimization of a Gas Chromatography/Mass Spectrometry Method and Application to
      Field Samples.
AB  - Biologic sample collection in wild cetacean populations is challenging. Most
      information on toxicant levels is obtained from blubber biopsy samples; however,
      sample collection is invasive and strictly regulated under permit, thus limiting
      sample numbers. Methods are needed to monitor toxicant levels that increase
      temporal and repeat sampling of individuals for population health and recovery
      models. The objective of this study was to optimize measuring trace levels (parts
      per billion) of persistent organic pollutants (POPs), namely polychlorinated
      biphenyls (PCBs), polybrominated-diphenyl-ethers (PBDEs),
      dichlorodiphenyltrichloroethanes (DDTs), and hexachlorocyclobenzene, in killer
      whale scat (fecal) samples. Archival scat samples, initially collected,
      lyophilized, and extracted with 70 % ethanol for hormone analyses, were used to
      analyze POP concentrations. The residual pellet was extracted and analyzed using
      gas chromatography coupled with mass spectrometry. Method detection limits ranged
      from 11 to 125 ng/g dry weight. The described method is suitable for p,p'-DDE,
      PCBs-138, 153, 180, and 187, and PBDEs-47 and 100; other POPs were below the
      limit of detection. We applied this method to 126 scat samples collected from
      Southern Resident killer whales. Scat samples from 22 adult whales also had known
      POP concentrations in blubber and demonstrated significant correlations (p <
      0.01) between matrices across target analytes. Overall, the scat toxicant
      measures matched previously reported patterns from blubber samples of decreased
      levels in reproductive-age females and a decreased p,p'-DDE/?PCB ratio in J-pod.
      Measuring toxicants in scat samples provides an unprecedented opportunity to
      noninvasively evaluate contaminant levels in wild cetacean populations; these
      data have the prospect to provide meaningful information for vital management
      decisions.

PMID- 26298466
TI  - Thrombospondin 1 as a novel biological marker of obesity and metabolic syndrome.
AB  - CONTEXT: Thrombospondin 1 (THBS1 or TSP-1) is an adipose-derived matricellular
      protein, which has recently been highlighted as a potential mediator of insulin
      resistance and adipose inflammation in obesity. OBJECTIVE: In this study, we
      aimed to determine the clinical significance of THBS1 as a novel biological
      marker of visceral obesity, metabolic syndrome, and diabetes. METHODS: The THBS1
      mRNA level was quantified with real-time PCR in human adipose tissues obtained
      from 16 non-obese subjects. The relationships between serum THBS1 level and
      obesity/diabetes traits as well as the diagnostic components of metabolic
      syndrome were assessed in 164 normal-weight or overweight/obese subjects (78
      males and 86 females; mean age, 50.4; mean BMI, 29.8) with analysis of covariance
      (ANCOVA) and regression analyses. RESULTS: THBS1 was predominantly expressed in
      visceral adipose tissues relative to subcutaneous adipose tissues (P<0.001). The
      visceral THBS1 expression was positively associated with the body mass index
      (BMI; gammas=0.54, P=0.033). ANCOVA demonstrated that the THBS1 level is
      associated with abdominal obesity (P<0.001), hyperglycemia (P=0.02), and
      hypertension (P=0.04). Multivariable regression analysis suggested an association
      between serum THBS1 and fasting plasma glucose levels. The associations between
      serum THBS1 levels and obesity/diabetes traits were found preferentially in women
      (BMI, gammas=0.30, P=0.05; FPG, gammas=0.26, P=0.016). Subanalyses demonstrated
      that the association with obesity traits was predominantly found in premenopausal
      women (BMI, gammas=0.41, P=0.007), whereas the association with diabetes traits
      was predominant in postmenopausal women (HbA1c, gammas=0.38, P=0.01). During
      medical weight reduction treatment, the change in the serum THBS1 level was
      associated with the change in BMI and HbA1c in pre- and postmenopausal women,
      respectively. CONCLUSIONS: Serum THBS1 is a useful biological marker of obesity
      and metabolic syndrome in Japanese subjects, particularly in women. THBS1 may act
      as a critical circulating factor that couples obesity with metabolic syndrome and
      diabetes in humans.

PMID- 26298467
TI  - Prognostic value of thyroid-stimulating hormone within reference range in
      patients with coronary artery disease.
AB  - BACKGROUND: Thyroid-stimulating hormone (TSH) in the upper part of reference
      range is associated with cardio-metabolic disorders. The association of TSH
      within reference range with prognosis of patients with coronary artery disease
      (CAD) after percutaneous coronary intervention (PCI) remains poorly investigated.
      METHODS: The study included 8010 consecutive patients with CAD who were treated
      with PCI. All patients had a TSH level within reference range (0.3 to 4.0 mU/L).
      The primary outcome was 3-year all-cause mortality. RESULTS: TSH tertiles were:
      1st tertile (0.3 mU/L to <1.02 mU/L; n=2694), 2nd tertile (1.02 mU/L to <1.67
      mU/L; n=2654) and 3rd tertile (1.67 mU/L to 4.00 mU/L; n=2662). The primary
      outcome (3-year mortality) occurred in 753 patients: 240 deaths in the 1st, 227
      deaths in the 2nd and 286 deaths in the 3rd TSH tertile (Kaplan-Meier estimates
      of mortality 10.2%, 9.8% and 12.3%; adjusted hazard ratio [HR]=1.31, 95%
      confidence interval [CI] 1.04-1.66 for each tertile increase). TSH level was
      associated with 30-day mortality (mortality estimates, 1.6% in the 1st, 1.6% in
      the 2nd and 3.5% in the 3rd TSH tertile; adjusted HR=2.30 [1.33-3.97] for each
      tertile increase) but not with 30-day to 3-year mortality (mortality estimates,
      8.6% in the 1st, 8.2% in the 2nd and 8.8% in the 3rd TSH tertile; P=0.603). The
      incidence of cardiogenic shock or peri-PCI bleeding was increased in patients in
      the upper TSH tertile. CONCLUSION: In patients with CAD undergoing PCI, TSH level
      in the upper part of reference range was associated with increased risk of
      mortality after PCI.

PMID- 26298468
TI  - Regional mosaic genomic heterogeneity in the elderly and in Alzheimer's disease
      as a correlate of neuronal vulnerability.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by
      fibrillary aggregates of Abeta peptide and tau protein. The distribution of these
      pathological hallmarks throughout the brain is not random; it follows a
      predictive pattern that is used for pathological staging. However, most
      etiopathogenetic concepts, irrespective of whether they focus on Abeta or tau
      pathology, leave a key question unanswered: what is the explanation for the
      different vulnerabilities of brain regions in AD? The pattern of regional
      progression of neurofibrillary degeneration in AD to some extent inversely
      recapitulates ontogenetic and phylogenetic brain development. Accordingly,
      degeneration preferentially affects brain areas that have recently been acquired
      or restructured during anthropoid evolution, which means that the involvement of
      a neurodevelopmental mechanism is highly likely. Since evolutionary expansion of
      the neocortex is based on a substantial extension of the mitotic activity of
      progenitor cells, we propose a conceptual link between neurogenesis in anthropoid
      primates and a higher risk of accumulating mitotic errors that give rise to
      genomic aberrations commonly referred to as DNA content variation (DCV). If
      increased rates of DCV make neurons more vulnerable to AD-related pathology, one
      might expect there to be a higher rate of DCV in areas that are affected very
      early during the course of AD, as compared to areas which are hardly affected or
      are affected only during the most advanced stages. Therefore, in the present
      study, we comparatively analyzed the DCV in five different cortical areas that
      are affected during the early stage (entorhinal cortex), the intermediate stage
      (temporal, frontal, and parietal association cortex), and the late stage (primary
      sensory occipital cortex) of AD in both normal elderly subjects and AD patients.
      On average, we observed about 10 % neuronal mosaic DCV in the normal elderly and
      a two- to threefold increase in DCV in AD patients. We were able to demonstrate,
      moreover, that the neuronal DCV in the cerebral cortex of the normal elderly as
      well as the increased neuronal DCV in AD patients are not randomly distributed
      but instead show systematic regional differences which correspond to differences
      in vulnerability. These findings provide additional evidence that mosaic genomic
      heterogeneity may play a key role in AD pathology. 

PMID- 26298469
TI  - Rab1-dependent ER-Golgi transport dysfunction is a common pathogenic mechanism in
      SOD1, TDP-43 and FUS-associated ALS.
AB  - Several diverse proteins are linked genetically/pathologically to
      neurodegeneration in amyotrophic lateral sclerosis (ALS) including SOD1, TDP-43
      and FUS. Using a variety of cellular and biochemical techniques, we demonstrate
      that ALS-associated mutant TDP-43, FUS and SOD1 inhibit protein transport between
      the endoplasmic reticulum (ER) and Golgi apparatus in neuronal cells. ER-Golgi
      transport was also inhibited in embryonic cortical and motor neurons obtained
      from a widely used animal model (SOD1(G93A) mice), validating this mechanism as
      an early event in disease. Each protein inhibited transport by distinct
      mechanisms, but each process was dependent on Rab1. Mutant TDP-43 and mutant FUS
      both inhibited the incorporation of secretory protein cargo into COPII vesicles
      as they bud from the ER, and inhibited transport from ER to the ER-Golgi
      intermediate (ERGIC) compartment. TDP-43 was detected on the cytoplasmic face of
      the ER membrane, whereas FUS was present within the ER, suggesting that transport
      is inhibited from the cytoplasm by mutant TDP-43, and from the ER by mutant FUS.
      In contrast, mutant SOD1 destabilised microtubules and inhibited transport from
      the ERGIC compartment to Golgi, but not from ER to ERGIC. Rab1 performs multiple
      roles in ER-Golgi transport, and over-expression of Rab1 restored ER-Golgi
      transport, and prevented ER stress, mSOD1 inclusion formation and induction of
      apoptosis, in cells expressing mutant TDP-43, FUS or SOD1. Rab1 also co-localised
      extensively with mutant TDP-43, FUS and SOD1 in neuronal cells, and Rab1 formed
      inclusions in motor neurons of spinal cords from sporadic ALS patients, which
      were positive for ubiquitinated TDP-43, implying that Rab1 is misfolded and
      dysfunctional in sporadic disease. These results demonstrate that ALS-mutant
      forms of TDP-43, FUS, and SOD1 all perturb protein transport in the early
      secretory pathway, between ER and Golgi compartments. These data also imply that
      restoring Rab1-mediated ER-Golgi transport is a novel therapeutic target in ALS. 

PMID- 26298470
TI  - The Relation between Severity of Autism and Caregiver-Child Interaction: a Study
      in the Context of Relationship Development Intervention.
AB  - The aim of this study was to examine the relations between severity of children's
      autism and qualities of parent-child interaction. We studied these variables at
      two points of time in children receiving a treatment that has a focus on social
      engagement, Relationship Development Intervention (RDI; Gutstein 2009).
      Participants were 18 parent-child dyads where the child (16 boys, 2 girls) had a
      diagnosis of autism and was between the ages of 2 and 12 years. The severity of
      the children's autism was assessed at baseline and later in treatment using the
      autism severity metric of the Autism Diagnostic Observation Schedule (ADOS;
      Gotham et al. Journal of Autism and Developmental Disorders, 39, 693-705 2009).
      Although the ADOS was designed as a diagnostic measure, ADOS calibrated severity
      scores (CSS) are increasingly used as one index of change (e.g., Locke et al.
      Autism, 18, 370-375 2014). Videotapes of parent-child interaction at baseline and
      later in treatment were rated by independent coders, for a) overall qualities of
      interpersonal relatedness using the Dyadic Coding Scales (DCS; Humber and Moss
      The American Journal of Orthopsychiatry, 75, 128-141 2005), and b) second-by
      second parent-child Co-Regulation and Intersubjective Engagement (processes
      targeted by the treatment approach of RDI). Severity of autism was correlated
      with lower quality of parent-child interaction. Ratings on each of these
      variables changed over the course of treatment, and there was evidence that
      improvement was specifically related to the quality of parent-child interaction
      at baseline. 

PMID- 26298471
TI  - Meat-eating by a wild Bornean orang-utan (Pongo pygmaeus).
AB  - We present the first evidence for consumption of meat by a wild Bornean orang
      utan (Pongo pygmaeus). Meat-eating has been reported in Sumatran orang-utans,
      specifically the hunting and consumption of slow lorises (Nycticebus coucang),
      but loris-hunting behaviour has not been observed in the Bornean species and meat
      of any species is essentially absent from their diet, with only two anecdotal
      reports of vertebrate meat consumption prior to this current finding in over 40
      years of study. In August 2012 an unhabituated adult flanged male orang-utan was
      observed eating an adult horse-tailed squirrel (Sundasciurus hippurus) carcass in
      the Sabangau peat-swamp forest, Central Kalimantan. We suspect this to be a case
      of scavenging, never reported previously in a Bornean orang-utan.

PMID- 26298472
TI  - Gait and Functional Mobility Deficits in Fragile X-Associated Tremor/Ataxia
      Syndrome.
AB  - Fragile X-associated tremor/ataxia syndrome (FXTAS) results from a "premutation"
      (PM) size CGG repeat expansion in the fragile X mental retardation 1 (FMR1) gene.
      Cerebellar gait ataxia is the primary feature in some FXTAS patients causing
      progressive disability. However, no studies have quantitatively characterized
      gait and mobility deficits in FXTAS. We performed quantitative gait and mobility
      analysis in seven FMR1 PM carriers with FXTAS and ataxia, six PM carriers without
      FXTAS, and 18 age-matched controls. We studied four independent gait domains,
      trunk range of motion (ROM), and movement transitions using an instrumented Timed
      Up and Go (i-TUG). We correlated these outcome measures with FMR1 molecular
      variables and clinical severity scales. PM carriers with FXTAS were globally
      impaired in every gait performance domain except trunk ROM compared to controls.
      These included total i-TUG duration, stride velocity, gait cycle time, cadence,
      double-limb support and swing phase times, turn duration, step time before turn,
      and turn-to-sit duration, and increased gait variability on several measures.
      Carriers without FXTAS did not differ from controls on any parameters, but double
      limb support time was close to significance. Balance and disability scales
      correlated with multiple gait and movement transition parameters, while the FXTAS
      Rating Scale did not. This is the first study to quantitatively examine gait and
      movement transitions in FXTAS patients. Gait characteristics were consistent with
      those from previous cohorts with cerebellar ataxia. Sensitive measures like the i
      TUG may help determine efficacy of interventions, characterize disease
      progression, and provide early markers of disease in FXTAS.

PMID- 26298473
TI  - The Cerebellum and Neurodevelopmental Disorders.
AB  - Cerebellar dysfunction is evident in several developmental disorders, including
      autism, attention deficit-hyperactivity disorder (ADHD), and developmental
      dyslexia, and damage to the cerebellum early in development can have long-term
      effects on movement, cognition, and affective regulation. Early cerebellar damage
      is often associated with poorer outcomes than cerebellar damage in adulthood,
      suggesting that the cerebellum is particularly important during development.
      Differences in cerebellar development and/or early cerebellar damage could impact
      a wide range of behaviors via the closed-loop circuits connecting the cerebellum
      with multiple cerebral cortical regions. Based on these anatomical circuits,
      behavioral outcomes should depend on which cerebro-cerebellar circuits are
      affected. Here, we briefly review cerebellar structural and functional
      differences in autism, ADHD, and developmental dyslexia, and discuss clinical
      outcomes following pediatric cerebellar damage. These data confirm the prediction
      that abnormalities in different cerebellar subregions produce behavioral symptoms
      related to the functional disruption of specific cerebro-cerebellar circuits.
      These circuits might also be crucial to structural brain development, as peri
      natal cerebellar lesions have been associated with impaired growth of the
      contralateral cerebral cortex. The specific contribution of the cerebellum to
      typical development may therefore involve the optimization of both the structure
      and function of cerebro-cerebellar circuits underlying skill acquisition in
      multiple domains; when this process is disrupted, particularly in early
      development, there could be long-term alterations of these neural circuits, with
      significant impacts on behavior. 

PMID- 26298474
TI  - Psychosis in Machado-Joseph Disease: Clinical Correlates, Pathophysiological
      Discussion, and Functional Brain Imaging. Expanding the Cerebellar Cognitive
      Affective Syndrome.
AB  - Machado-Joseph disease (MJD) is the most common spinocerebellar ataxia worldwide
      with a broad range of clinical manifestations, but psychotic symptoms were not
      previously characterized. We investigated the psychiatric manifestations of a
      large cohort of Brazilian patients with MJD in an attempt to characterize the
      presence of psychotic symptoms. We evaluated 112 patients with clinical and
      molecular diagnosis of MJD from February 2008 to November 2013. Patients with
      psychotic symptoms were referred to psychiatric evaluation and brain perfusion
      single-photon emission computed tomography (SPECT) analysis. A specific scale
      Positive and Negative Syndrome Scale (PANSS)-was used to characterize psychotic
      symptoms in MJD patients. We also performed an autopsy from one of the patients
      with MJD and psychotic symptoms. Five patients presented psychotic symptoms.
      Patients with psychotic symptoms were older and had a late onset of the disease
      (p < 0.05). SPECT results showed that MJD patients had significant regional
      cerebral blood flow (rCBF) decrease in the cerebellum bilaterally and vermis
      compared with healthy subjects. No significant rCBF differences were found in
      patients without psychotic symptoms compared to patients with psychotic symptoms.
      The pathological description of a patient with MJD and psychotic symptoms
      revealed severe loss of neuron bodies in the dentate nucleus and substantia
      nigra. MJD patients with a late onset of the disease and older ones are at risk
      to develop psychotic symptoms during the disease progression. These clinical
      findings may be markers for an underlying cortical-cerebellar disconnection or
      degeneration of specific cortical and subcortical regions that may characterize
      the cerebellar cognitive affective syndrome. 

PMID- 26298475
TI  - Heavy Drinking and Social and Health Factors in University Students from 24 Low,
      Middle Income and Emerging Economy Countries.
AB  - The aim of this study was to investigate heavy drinking and social and health
      correlates in university students in low, middle income and emerging economy
      countries. Using anonymous questionnaires, data were collected in a cross
      sectional survey of 17,590 undergraduate university students (mean age 20.8, SD
      2.9) from 25 universities in 24 countries across Asia, Africa and the Americas.
      Overall, 71.6 % were non-drinkers, 17.1 % moderate and 11.3 % heavy alcohol
      drinkers (14.2 % in men and 9.2 % in women) in the past 2 weeks. In a
      multivariate logistic regression analysis, older age, poorer family background,
      living in a higher income country, weak beliefs in the importance of limiting
      alcohol use, higher country per capita alcohol consumption, other substance use
      (tobacco and illicit drug use), and poor life satisfaction was associated with
      heavy drinking. Addressing health beliefs and co-occurring addictive behaviors
      may be crucial in the prevention of heavy drinking in this population. 

PMID- 26298476
TI  - Cognitive Behavioral Therapy for Psychosis (CBT-p) Delivered in a Community
      Mental Health Setting: A Case Comparison of Clients Receiving CBT Informed
      Strategies by Case Managers Prior to Therapy.
AB  - This exploratory case comparison examines the influence of case management
      activities on engagement and progress in psychotherapy for clients with
      schizophrenia. Six clients were recruited to participate in ten sessions of
      Cognitive Behavioral Therapy for psychosis (CBT-p). Three clients who had
      received Cognitive Behavioral techniques for psychosis (CBt-p, a low-intensity
      case management intervention) prior to receiving therapy were selected from
      referrals. A comparison group of three clients who had received standard case
      management services was selected from referrals. Cases within and across groups
      were compared on outcome measures and observations from case review were offered
      to inform future research. Delivering CBT-p services on a continuum from low- to
      high-intensity is discussed.

PMID- 26298477
TI  - Current and forthcoming approaches for systemic detoxification.

PMID- 26298478
TI  - Platelet concentrates in spine fusion: meta-analysis of union rates and
      complications in controlled trials.
AB  - PURPOSE: Platelet concentrates in spine fusion gained increasing popularity among
      spine surgeons. They avoid morbidity of bone harvest and promise good union rates
      without additional device-related adverse events. Therefore, they seem to be a
      safe and effective alternative to common bone substitutes. This meta-analysis
      assesses the available evidence for union rate and overall complications with the
      use of platelet concentrates in spine fusion. METHODS: We conducted an online
      search for relevant controlled trials and extracted data on union rates,
      complications, and revision rates. These data were synthesized in a meta-analysis
      using fixed-effects odds ratios (OR). To assess covariates, meta-regression was
      performed as well. RESULTS: Our search produced 166 results, ten of which were
      eligible for inclusion. These studies report on a total of 763 patients (328
      experimental, 435 controls) with a mean age of 50.3 +/- 7.5 years. Mean follow-up
      was 1.9 +/- 0.0.4 years. With the use of platelet concentrates, union rate
      decreased significantly, OR 0.53 (95 % CI 0.35-0.79, p = 0.002), compared with
      the control group. There was no statistically significant difference in
      complication rates OR 1.34 (95 % CI 0.62-2.90, p = 0.46) or in revision rates OR
      3.0 (95 % CI 0.90-10.00, p = 0.74). Meta-regression showed no statistically
      significant influence of randomization, Jadad score, or assessment of fusion.
      CONCLUSION: The use of platelet concentrates in spine fusion shows significantly
      decreased union rates compared with the control group. However, complication and
      revision rates were not significantly increased. The current data do not
      recommend the use of platelet concentrate in spine fusion.

PMID- 26298480
TI  - Carbon-ion radiotherapy of spinal osteosarcoma with long-term follow.
AB  - PURPOSE: Primary spinal osteosarcoma is quite rare, and the 5-year survival rate
      is very low. Because of its rarity, successful treatment experience with spinal
      osteosarcoma is limited. The purpose of this study is to report the effect of
      therapy of primary osteosarcoma of spine by carbon-ion radiotherapy (CIRT) and
      long-term follow. METHODS: A 70-year-old with primary spinal osteosarcoma who
      received CIRT underwent combined anterior artificial vertebral body replacement
      and posterior lumbar fusion (L1-L5) 3 years later. RESULTS: According to the
      surgical resection of tumoral lesion, pathological results showed that the
      intertrabecular space previously filled with tumor cells on the initial biopsy
      sample now contained necrotic tissue without tumor cells. This means that primary
      osteosarcoma of the spine was completely eliminated and achieved local control
      with CIRT, with a 7-year follow-up after the initial treatment. CONCLUSIONS:
      Carbon ion beam treatment is an effective local treatment for patients with
      spinal osteosarcoma for whom surgical resection is not a feasible option,
      especially for elderly patients. However, more patients need to be evaluated over
      a longer term to assess the curative effect of CIRT.

PMID- 26298479
TI  - Minimally invasive cervical foraminotomy and diskectomy for laterally located
      soft disk herniation.
AB  - PURPOSE: The posterior cervical foraminotomy and diskectomy (PCD) is a
      traditional surgical technique for patients with laterally located soft-disk
      herniation. Recently, tubular retractor-assisted posterior foraminotomy and
      diskectomy (MTPF) and posterior percutaneous endoscopic cervical foraminotomy and
      diskectomy (P-PECD) have been introduced, but a comparative study has not yet
      been performed. METHODS: Patients with foraminal soft-disk herniation and a
      follow-up period of >2 years were retrospectively reviewed; 22 patients underwent
      a MTPF and 22 patients underwent a P-PECD. The primary end-point was an
      improvement of arm pain more than 4.3. The clinical parameters (age, sex,
      disability index, neck and arm pain), radiological parameters (cervical
      curvature, segmental angle, anterior-/posterior-disk height and amount of facet
      joint removal) preoperatively and at postoperative month 24 and the surgical
      methods were considered as co-variates. RESULTS: Successful outcome was achieved
      in 19/22 (87%) of the patients after both MTPF and a P-PECD. Preoperative SA
      showed trend (P = 0.08; OR 1.2; 95% CI 0.98-1.4) and the cut-off SA was 1.45
      degrees  (sensitivity 80%, specificity 73%). The length of the facet joint's
      removal was 0.02-2.49 mm (0.1-15.2%) with no difference between the MTPF and P
      PECD. The surgical method was not a significant factor. CONCLUSIONS: For patients
      with foraminal soft-disk herniation, either MTPF or P-PECD, may be regarded as an
      alternative options to open surgery. Preoperative kyphotic SA (cut-off value 1.45
      degrees ) seemed to be associated with poor outcome and this may be considered in
      selecting surgical methods.

PMID- 26298482
TI  - Solid recovered fuel: An experiment on classification and potential applications.
AB  - The residual urban waste of Prato district (Italy) is characterized by a high
      calorific value that would make it suitable for direct combustion in waste-to
      energy plants. Since the area of central Italy lacks this kind of plant, residual
      municipal waste is quite often allocated to mechanical treatment plants in order
      to recover recyclable materials (such as metals) and energy content, sending the
      dry fractions to waste-to-energy plants outside the region. With the previous
      Italian legislation concerning Refuse Derived Fuels, only the dry stream produced
      as output by the study case plant, considered in this study, could be allocated
      to energy recovery, while the other output flows were landfilled. The most recent
      Italian regulation, introduced a new classification for the fuel streams
      recovered from waste following the criteria of the European standard (EN
      15359:2011), defining the Solid Recovered Fuel (SRF). In this framework, the aim
      of this study was to check whether the different streams produced as output by
      the study case plant could be classified as SRF. For this reason, a sampling and
      analysis campaign was carried out with the purpose of characterizing every single
      output stream that can be obtained from the study case mechanical treatment
      plant, when operating it in different ways. The results showed that all the
      output flows from the study case mechanical treatment plant were classified as
      SRF, although with a wide quality range. In particular, few streams, of rather
      poor quality, could be fed to waste-to-energy plants, compatibly with the plant
      feeding systems. Other streams, with very high quality, were suitable for non
      dedicated facilities, such as cement plants or power plants, as a substitute for
      coal. The implementation of the new legislation has hence the potential for a
      significant reduction of landfilling, contributing to lowering the overall
      environmental impact by avoiding the direct impacts of landfilling and by
      exploiting the beneficial effects of energy recovery from waste. 

PMID- 26298481
TI  - Secondary Metastases Resection After Bevacizumab Plus Irinotecan-Based
      Chemotherapy in First-Line Therapy of Metastatic Colorectal Cancer in a Real-Life
      Setting: Results of the ETNA Cohort.
AB  - PURPOSE: Resection of metastases after chemotherapy improves survival outcomes of
      patients with initially inoperable metastatic colorectal cancer (mCRC), yet
      little data is available for those treated in the first-line setting with
      bevacizumab plus irinotecan. To provide data on this, the present study described
      the subgroup of the ETNA cohort who underwent metastases surgery. METHODS: The
      population of operated patients was described according to metastatic site
      (exclusively hepatic, non-exclusively hepatic, and non-hepatic). Factors
      associated with overall survival (OS) and progression-free survival (PFS) were
      evaluated using multivariable Cox analysis. RESULTS: A total of 76 patients (21.1
      % of the ETNA cohort) underwent metastases resection: 50 % male, median age 61.9
      years, 85.5 % ECOG  <= 1, and median duration of bevacizumab use 7.2 months. No
      surgery-related deaths were observed and 30.6 % of patients had at least one post
      operative complication, mainly infections (11.8 % of resections), bleeding
      complications (3.5 %), or delayed wound healing (2.4 %). Complete remission was
      higher for those with exclusively hepatic metastases (22/32, 68.8 %) than those
      with non-exclusively hepatic metastases (12/24, 50.0 %), or non-hepatic
      metastases (12/20, 60.0 %). Among operated patients, 52.6 % had died after 5
      years of follow-up. In multivariable analysis at 2 years of follow-up, death (HR
      0.09 [95 % CI 0.02-0.35]) and progression (HR 0.35 [95 % CI 0.23-0.56]) were less
      likely for patients with complete remission (CR) after surgery R0-R1 or
      radiofrequency ablation (RFA) [CR RFA] compared with those who were not resected
      or with R2 resection. CONCLUSION: In real-life practice, bevacizumab with
      irinotecan in first-line therapy for mCRC allows secondary resection of
      metastases and survival is more favourable in those with complete remission (R0
      R1/CR RFA).

PMID- 26298483
TI  - Methane oxidation potential of boreal landfill cover materials: The governing
      factors and enhancement by nutrient manipulation.
AB  - Methanotrophs inhabiting landfill covers are in a crucial role in mitigating CH4
      emissions, but the characteristics of the cover material or ambient temperature
      do not always enable the maximal CH4 oxidation potential (MOP). This study aimed
      at identifying the factors governing MOPs of different materials used for
      constructing biocovers and other cover structures. We also tested whether the
      activity of methanotrophs could be enhanced at cold temperature (4 and 12 degrees
      C) by improving the nutrient content (NO3(-), PO4(3-), trace elements) of the
      cover material. Compost samples from biocovers designed to support CH4 oxidation
      were exhibiting the highest MOPs (4.16 MUmol CH4 g dw(-1) h(-1)), but also the
      soil samples collected from other cover structures were oxidising CH4 (0.41 MUmol
      CH4 g dw(-1) h(-1)). The best predictors for the MOPs were the NO3(-) content and
      activity of heterotrophic bacteria at 72.8%, which were higher in the compost
      samples than in the soil samples. The depletion of NO3(-) from the landfill cover
      material limiting the activity of methanotrophs could not be confirmed by the
      nutrient manipulation assay at 4 degrees C as the addition of nitrogen decreased
      the MOPs from 0.090 MUmol CH4 g dw(-1) h(-1) to <0.085 MUmol CH4 g dw(-1) h(-1).
      At 12 degrees C, all nutrient additions reduced the MOPs. The inhibition was
      believed to result from high ionic concentration caused by nutrient addition. At
      4 degrees C, the addition of trace elements increased the MOPs (>0.096 MUmol CH4
      g dw(-1)h(-1)) suggesting that this was attributable to stimulation of the
      enzymatic activity of the psychrotolerant methanotrophs.

PMID- 26298484
TI  - Curcumin promotes fibril formation in F isomer of human serum albumin via
      amorphous aggregation.
AB  - We here describe the amyloid fibrils promoting behavior of curcumin, which
      ability to inhibit amyloid fibrillization of several globular proteins is well
      documented. Transmission electron microscopy (TEM), 90 degrees  light scattering
      (RLS), thioflavine T (ThT) and Congo red (CR) binding studies demonstrated that
      both F (pH3.4) and E (pH1.8) isomers of human serum albumin (HSA) in the absence
      and presence of curcumin initially converted into amorphous aggregates.
      Interestingly, only the sample containing F isomer preincubated with curcumin
      formed fibrils on incubation for longer period. We also found that curcumin
      strongly bind to the F isomer, alter its secondary, tertiary structures and
      thermal stability. We conclude that the conversion of intermediate states into
      amorphous aggregate to fibrils is dictated by its conformation. This study
      provides unique insights into ligand-controlled HSA aggregation pathway and
      should provide a useful model system to study both amorphous and the fibrillar
      aggregation of multidomain proteins. 

PMID- 26298485
TI  - Percutaneous Pericardial Effusion Drainage under Ultrasonographic and
      Fluoroscopic Guidance for Symptomatic Pericardial Effusion: A Single-Center
      Experience in 93 Consecutive Patients.
AB  - PURPOSE: To evaluate the safety and efficacy of ultrasound-guided and
      fluoroscopically guided percutaneous pericardial effusion drainage as performed
      by interventional radiologists in patients with symptomatic pericardial effusion.
      MATERIALS AND METHODS: From July 2002 to December 2013, 93 patients were treated
      with percutaneous pericardial effusion drainage. Pericardial effusion drainage
      was performed via 3 routes: apical, subxiphoid, and transhepatic routes. After
      puncturing the pericardial sac with a 22-gauge needle under ultrasound guidance,
      a drainage catheter was inserted under fluoroscopic guidance. Pericardial
      effusion was categorized according to its distribution in the pericardial cavity:
      "circumferential even," "circumferential uneven" (predominant site specified),
      and "loculated." Technical success, recurrence, and complication rates were
      assessed. RESULTS: The technical success rate was 99%. Pericardial effusion
      drainage was performed via the subxiphoid approach in 54 procedures, transhepatic
      approach in 30 procedures, and apical approach in 13 procedures. The transhepatic
      approach was mainly performed in cases where the effusion was distributed
      posteriorly to the heart (80%). One patient died of uncontrolled hypotension
      without evidence of hemopericardium. CONCLUSIONS: Ultrasound-guided and
      fluoroscopically guided pericardial effusion drainage is a safe and effective
      procedure for patients with symptomatic pericardial effusion. The transhepatic
      approach may be preferable for posteriorly distributed pericardial effusion that
      would otherwise be inaccessible by a traditional subxiphoid or apical approach.

PMID- 26298486
TI  - Exploring the color feature power for psoriasis risk stratification and
      classification: A data mining paradigm.
AB  - A large percentage of dermatologist's decision in psoriasis disease assessment is
      based on color. The current computer-aided diagnosis systems for psoriasis risk
      stratification and classification lack the vigor of color paradigm. The paper
      presents an automated psoriasis computer-aided diagnosis (pCAD) system for
      classification of psoriasis skin images into psoriatic lesion and healthy skin,
      which solves the two major challenges: (i) fulfills the color feature
      requirements and (ii) selects the powerful dominant color features while
      retaining high classification accuracy. Fourteen color spaces are discovered for
      psoriasis disease analysis leading to 86 color features. The pCAD system is
      implemented in a support vector-based machine learning framework where the
      offline image data set is used for computing machine learning offline color
      machine learning parameters. These are then used for transformation of the online
      color features to predict the class labels for healthy vs. diseased cases. The
      above paradigm uses principal component analysis for color feature selection of
      dominant features, keeping the original color feature unaltered. Using the cross
      validation protocol, the above machine learning protocol is compared against the
      standalone grayscale features with 60 features and against the combined grayscale
      and color feature set of 146. Using a fixed data size of 540 images with equal
      number of healthy and diseased, 10 fold cross-validation protocol, and SVM of
      polynomial kernel of type two, pCAD system shows an accuracy of 99.94% with
      sensitivity and specificity of 99.93% and 99.96%. Using a varying data size
      protocol, the mean classification accuracies for color, grayscale, and combined
      scenarios are: 92.85%, 93.83% and 93.99%, respectively. The reliability of the
      system in these three scenarios are: 94.42%, 97.39% and 96.00%, respectively. We
      conclude that pCAD system using color space alone is compatible to grayscale
      space or combined color and grayscale spaces. We validated our pCAD system
      against facial color databases and the results are consistent in accuracy and
      reliability. 

PMID- 26298487
TI  - Differential cryptanalysis of a medical image cryptosystem with multiple rounds.
AB  - Recently, Fu et al. proposed a chaos-based medical image encryption scheme that
      has permutation-substitution architecture. The authors believe that the scheme
      with bit-level cat map shuffling can be achieved at high level of security even
      if it is only applied with a few encryption rounds. However, we find that the
      scheme cannot resist differential cryptanalysis. The differential cryptanalysis
      shows that the security of the original scheme depends only on permutation key
      instead of on all of the keys. Moreover, 17 chosen plain-images can reveal
      equivalent permutation key for 1-round and 2-round encryption. We propose a novel
      analysis method called double differential cryptanalysis comparison (DDCC) that
      is valid to break multi-round encryption with 16N(2)+1 chosen plain-images, where
      N(2) is the size of the image. We also point out several weaknesses of the
      cryptosystem. The theoretical analysis and simulation results indicate that the
      encryption scheme is insecure. 

PMID- 26298488
TI  - A clinical decision support system for diagnosis of Allergic Rhinitis based on
      intradermal skin tests.
AB  - BACKGROUNDS AND OBJECTIVES: Allergic Rhinitis is a universal common disease,
      especially in populated cities and urban areas. Diagnosis and treatment of
      Allergic Rhinitis will improve the quality of life of allergic patients. Though
      skin tests remain the gold standard test for diagnosis of allergic disorders,
      clinical experts are required for accurate interpretation of test outcomes. This
      work presents a clinical decision support system (CDSS) to assist junior
      clinicians in the diagnosis of Allergic Rhinitis. METHODS: Intradermal Skin tests
      were performed on patients who had plausible allergic symptoms. Based on
      patient's history, 40 clinically relevant allergens were tested. 872 patients who
      had allergic symptoms were considered for this study. The rule based
      classification approach and the clinical test results were used to develop and
      validate the CDSS. Clinical relevance of the CDSS was compared with the Score for
      Allergic Rhinitis (SFAR). Tests were conducted for junior clinicians to assess
      their diagnostic capability in the absence of an expert. RESULTS: The class based
      Association rule generation approach provides a concise set of rules that is
      further validated by clinical experts. The interpretations of the experts are
      considered as the gold standard. The CDSS diagnoses the presence or absence of
      rhinitis with an accuracy of 88.31%. The allergy specialist and the junior
      clinicians prefer the rule based approach for its comprehendible knowledge model.
      CONCLUSION: The Clinical Decision Support Systems with rule based classification
      approach assists junior doctors and clinicians in the diagnosis of Allergic
      Rhinitis to make reliable decisions based on the reports of intradermal skin
      tests.

PMID- 26298489
TI  - Investigations on the role of CH...O interactions and its impact on stability and
      specificity of penicillin binding proteins.
AB  - Penicillin binding proteins are recognized as important antibacterial targets
      because of their crucial role in the cell wall synthesis of bacteria. Alteration
      in the binding site of penicillin binding proteins is one of the major problems
      for beta lactam antibiotics to exert its effect. In the present study the
      influence of CH...O interactions in the conformational stability of penicillin
      binding proteins were analyzed in both Gram positive and Gram negative bacteria.
      CH...O interactions constitute about 20 to 25% of total hydrogen bonds and act as
      an important driving force in ligand selectivity. From our analysis we observed a
      total of 13,398 CH...O interactions in Gram positive bacteria and 10,855 CH...O
      interactions in Gram negative bacteria. It was interesting to observe that CH...O
      interactions were higher in Gram positive bacteria than in Gram negative
      bacteria, which augurs well for the discrepancy in cell wall of the bacteria.
      CH...O interactions are classified into four types depending on the interaction
      of acceptor residues with the back bone or side chain of CH groups. From our
      results we observed that major contribution to penicillin binding proteins was
      observed from side chain atoms of donor residues and back bone atoms of acceptor
      residues [SM CH...O] in both Gram positive and Gram negative bacteria.
      Conformational preference of Gram positive bacteria indicated that amino acids
      lacking side chain and the cyclized amino acids preferred to be in turn regions,
      whereas aromatic amino acids dominated in Gram negative bacteria. Our analysis
      gives detailed information about the principles involved in the conformational
      stability of penicillin binding proteins and the results will be useful for
      researchers exploring penicillin binding proteins. 

PMID- 26298490
TI  - A reduction of the saddle vertical force triggers the sit-stand transition in
      cycling.
AB  - The purpose of the study was to establish the link between the saddle vertical
      force and its determinants in order to establish the strategies that could
      trigger the sit-stand transition. We hypothesized that the minimum saddle
      vertical force would be a critical parameter influencing the sit-stand transition
      during cycling. Twenty-five non-cyclists were asked to pedal at six different
      power outputs from 20% (1.6 +/- 0.3 W kg(-1)) to 120% (9.6 +/- 1.6 W kg(-1)) of
      their spontaneous sit-stand transition power obtained at 90 rpm. Five 6-component
      sensors (saddle tube, pedals and handlebars) and a full-body kinematic
      reconstruction were used to provide the saddle vertical force and other force
      components (trunk inertial force, hips and shoulders reaction forces, and trunk
      weight) linked to the saddle vertical force. Minimum saddle vertical force
      linearly decreased with power output by 87% from a static position on the bicycle
      (5.30 +/- 0.50 N kg(-1)) to power output=120% of the sit-stand transition power
      (0.68 +/- 0.49 N kg(-1)). This decrease was mainly explained by the increase in
      instantaneous pedal forces from 2.84 +/- 0.58 N kg(-1) to 6.57 +/- 1.02 N kg(-1)
      from 20% to 120% of the power output corresponding to the sit-stand transition,
      causing an increase in hip vertical forces from -0.17 N kg(-1) to 3.29 N kg(-1).
      The emergence of strategies aiming at counteracting the elevation of the trunk
      (handlebars and pedals pulling) coincided with the spontaneous sit-stand
      transition power. The present data suggest that the large decrease in minimum
      saddle vertical force observed at high pedal reaction forces might trigger the
      sit-stand transition in cycling.

PMID- 26298491
TI  - 3D shoulder kinematics for static vs dynamic and passive vs active testing
      conditions.
AB  - Shoulder motion analysis provides clinicians with references of normal joint
      rotations. Shoulder joints orientations assessment is often based on series of
      static positions, while clinicians perform either passive or active tests and
      exercises mostly in dynamic. These conditions of motion could modify joint
      coordination and lead to discrepancies with the established references. Hence,
      the objective was to evaluate the influence of static vs dynamic and passive vs
      active testing conditions on shoulder joints orientations. Twenty asymptomatic
      subjects setup with 45 markers on the upper limb and trunk were tracked by an
      optoelectronic system. Static positions (30 degrees , 60 degrees , 90 degrees 
      and 120 degrees  of thoracohumeral elevation) and dynamic motion both in active
      condition and passively mobilised by an examiner were executed. Three-dimensional
      sternoclavicular, acromioclavicular, scapulothoracic and glenohumeral joint
      angles (12 in total) representing the distal segment orientation relative to the
      proximal segment orientation were estimated using a shoulder kinematical chain
      model. Separate four-way repeated measures ANOVA were applied on the 12 joint
      angles with factors of static vs dynamic, passive vs active, thoracohumeral
      elevation angle (30 degrees , 60 degrees , 90 degrees  and 120 degrees ) and
      plane of elevation (frontal and sagittal). Scapulothoracic lateral rotation
      progressed more during arm elevation in static than in dynamic gaining 4.2
      degrees  more, and also in passive than in active by 6.6 degrees . Glenohumeral
      elevation increased more during arm elevation in active than in passive by 4.4
      degrees . Shoulder joints orientations are affected by the testing conditions,
      which should be taken into consideration for data acquisition, inter-study
      comparison or clinical applications.

PMID- 26298492
TI  - The effect of resolution on viscous dissipation measured with 4D flow MRI in
      patients with Fontan circulation: Evaluation using computational fluid dynamics.
AB  - Viscous dissipation inside Fontan circulation, a parameter associated with the
      exercise intolerance of Fontan patients, can be derived from computational fluid
      dynamics (CFD) or 4D flow MRI velocities. However, the impact of spatial
      resolution and measurement noise on the estimation of viscous dissipation is
      unclear. Our aim was to evaluate the influence of these parameters on viscous
      dissipation calculation. Six Fontan patients underwent whole heart 4D flow MRI.
      Subject-specific CFD simulations were performed. The CFD velocities were down
      sampled to isotropic spatial resolutions of 0.5mm, 1mm, 2mm and to MRI
      resolution. Viscous dissipation was compared between (1) high resolution CFD
      velocities, (2) CFD velocities down-sampled to MRI resolution, (3) down-sampled
      CFD velocities with MRI mimicked noise levels, and (4) in-vivo 4D flow MRI
      velocities. Relative viscous dissipation between subjects was also calculated. 4D
      flow MRI velocities (15.6 +/- 3.8 cm/s) were higher, although not significantly
      different than CFD velocities (13.8 +/- 4.7 cm/s, p=0.16), down-sampled CFD
      velocities (12.3 +/- 4.4 cm/s, p=0.06) and the down-sampled CFD velocities with
      noise (13.2 +/- 4.2 cm/s, p=0.06). CFD-based viscous dissipation (0.81 +/- 0.55
      mW) was significantly higher than those based on down-sampled CFD (0.25 +/- 0.19
      mW, p=0.03), down-sampled CFD with noise (0.49 +/- 0.26 mW, p=0.03) and 4D flow
      MRI (0.56 +/- 0.28 mW, p=0.06). Nevertheless, relative viscous dissipation
      between different subjects was maintained irrespective of resolution and noise,
      suggesting that comparison of viscous dissipation between patients is still
      possible.

PMID- 26298493
TI  - Conformationally restrained carbamoylcholine homologues. Synthesis, pharmacology
      at neuronal nicotinic acetylcholine receptors and biostructural considerations.
AB  - Exploration of small selective ligands for the nicotinic acetylcholine receptors
      (nAChRs) based on acetylcholine (ACh) has led to the development of potent
      agonists with clear preference for the alpha4beta2 nAChR, the most prevalent
      nAChR subtype in the central nervous system. In this work we present the
      continuation of these efforts aimed at increasing this subtype selectivity by
      introduction of conformational restriction in the carbamoylcholine homologue, 3
      (dimethylaminobutyl) dimethylcarbamate (DMABC). Our results highlight the
      importance of the N-carbamoyl substitution in alpha4beta2-subtype selectivity.
      Moreover, we have confirmed the non-linear conformation of DMABC bound to nAChRs
      suggested by recent crystal structures of the compound in complex with the
      Lymnaea stagnalis ACh binding protein.

PMID- 26298494
TI  - Design, synthesis of novel tryptophan derivatives for antiplatelet aggregation
      activity based on tripeptide pENW (pGlu-Asn-Trp).
AB  - pENW, a three mer peptide derived from Agkistrodon acutus Guenther venom, has
      been found to be an antagonist of the GPIIb/IIIa receptor and shows antiplatelet
      aggregation activity. Based on pENW and a GPIIb/IIIa inhibitor Tirofiban, a
      series of tryptophan derivatives were designed, synthesized and evaluated for
      their antiplatelet aggregation activity induced by ADP. The most potent compound
      87 was also tested for the bleeding time and antithrombotic activity in vivo in
      comparison with Tirofiban. The results indicated that 87 shows similar
      antiplatelet aggregation activity as Tirofiban to the aggregation of platelet
      induced by all of the four agonists, but has lower bleeding risk than Tirofiban,
      representing a promising lead compound for further study. 

PMID- 26298495
TI  - Expanding the structural diversity of Bcr-Abl inhibitors: Hybrid molecules based
      on GNF-2 and Imatinib.
AB  - In order to expand the structural diversity of Bcr-Abl inhibitors, twenty hybrids
      (series E and P) have been synthesized and characterized based on Imatinib and
      GNF-2. Their biological activities were evaluated in vitro against human leukemia
      cells. Most compounds exhibited potent antiproliferative activity against K562
      cells, especially for compounds E4, E5 and E7. Furthermore, these new hybrids
      were also screened for Abl kinase inhibitory activity, and some of them inhibited
      Abl kinase with low micromolar IC50 values. In particular, compound P3 displayed
      the most potent activity with IC50 value of 0.017 MUM comparable with that of
      Imatinib. Molecular docking studies indicated that these novel hybrids fitted
      well with the active site of Bcr-Abl. These results suggested the great potential
      of these compounds as novel Bcr-Abl inhibitors.

PMID- 26298496
TI  - Discovery of novel 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine derivatives
      as gamma-secretase modulators.
AB  - Novel 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine derivatives were designed,
      synthesized, and evaluated as gamma-secretase modulators (GSMs). An optimization
      study of this series resulted in the identification of (R)-11j, which showed a
      potent Abeta42-lowering effect, high bioavailability and good blood-brain barrier
      permeability in mice. Oral administration of (R)-11j significantly reduced brain
      Abeta42 in mice at a dose of 10 mg/kg.

PMID- 26298497
TI  - Recent progress on MAP kinase pathway inhibitors.
AB  - The RAS-RAF-MEK-ERK, or ERK signaling pathway propagates signals through an
      intracellular signal transduction cascade. Since approximately one third of human
      cancers are impacted by mutations in the ERK signaling pathway, intensive efforts
      to develop drugs targeting members of this cascade are ongoing. While efforts to
      develop drugs aimed at inhibiting RAS are still at an early stage, substantial
      progress in discovering clinical drugs targeting RAF, MEK, and ERK have been
      made. This review will highlight the recent progress in this area. 

PMID- 26298498
TI  - Design and synthesis of carborane-containing estrogen receptor-beta (ERbeta)
      selective ligands.
AB  - Candidates for highly selective estrogen receptor-beta (ERbeta) ligands (6a-c, 7a
      c, 8a and 8b) were designed and synthesized based on carborane-containing ER
      ligands 1 and 2 as lead compounds. Among them, p-carboranylcyclohexanol
      derivatives 8a and 8b exhibited high ERbeta selectivity in competitive binding
      assay: for example, 8a showed 56-fold selectivity for ERbeta over ERalpha.
      Docking studies of 8a and 8b with the ERalpha and ERbeta ligand-binding domains
      (LBDs) suggested that the p-carborane cage of the ligands is located close to key
      amino acid residues that influence ER-subtype selectivity, that is, Leu384 in the
      ERalpha LBD and Met336 in the ERbeta LBD. The p-carborane cage in 8a and 8b
      appears to play a crucial role in the increased ERbeta selectivity. 

PMID- 26298499
TI  - The imidazo[1,2-a]pyridine ring system as a scaffold for potent dual
      phosphoinositide-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitors.
AB  - Based on lead compound 1, which was discovered from a high-throughput screen, a
      series of PI3Kalpha/mTOR inhibitors were evaluated that contained an imidazo[1,2
      a]pyridine as a core replacement for the benzimidazole contained in 1. By
      exploring various ring systems that occupy the affinity pocket, two fragments
      containing a methoxypyridine were identified that gave <100 nM potency toward
      PI3Kalpha in enzyme and cellular assays with moderate stability in rat and human
      liver microsomes. With the two methoxypyridine groups selected to occupy the
      affinity pocket, analogs were prepared with various fragments intended to occupy
      the ribose pocket of PI3Kalpha and mTOR. From these analogs, tertiary alcohol 18
      was chosen for in vivo pharmacodynamic evaluation based on its potency in the
      PI3Kalpha cellular assay, microsomal stability, and in vivo pharmacokinetic
      properties. In a mouse liver pharmacodynamic assay, compound 18 showed 56%
      inhibition of HFG-induced AKT (Ser473) phosphorylation at a 30 mg/kg dose.

PMID- 26298500
TI  - One-pot synthesis of new triazole--Imidazo[2,1-b][1,3,4]thiadiazole hybrids via
      click chemistry and evaluation of their antitubercular activity.
AB  - A new series of triazole-imidazo[2,1-b][1,3,4]thiadiazole hybrids (6a-s, 7a) were
      designed by a molecular hybridisation approach and the target molecules were
      synthesized via one pot click chemistry protocol. All the intermediates and final
      molecules were characterised using spectral methods and one of the target
      compounds (6c) was analysed by the single crystal XRD study. The derivatives were
      screened for their antimycobacterial activity against Mycobacterium tuberculosis
      H37Rv strain. Two compounds, 6f and 6n, demonstrated significant growth
      inhibitory activity against the bacterial strain with a MIC of 3.125 MUg/mL. The
      presence of chloro substituent on the imidazo[2,1-b][1,3,4]thiadiazole ring and
      ethyl, benzyl or cyanomethylene groups on the 1,2,3-triazole ring enhance the
      inhibition activity of the molecules. The active compounds are not toxic to a
      normal cell line which signifies the lack of general cellular toxicity of these
      compounds.

PMID- 26298502
TI  - Striatal contributions to sensory timing: Voxel-based lesion mapping of
      electrophysiological markers.
AB  - To achieve precise timing, the brain needs to establish a representation of the
      temporal structure of sensory input and use this information to generate timely
      responses. These operations engage the basal ganglia. Current research in this
      direction is limited by reliance on animal models, motor and/or offline tasks,
      small sample sizes, the low temporal resolution of functional magnetic resonance
      imaging, and the study of progressive neurodegeneration. Here, we combine the
      excellent temporal resolution of electrophysiological potentials with the high
      spatial resolution of structural neuroimaging to investigate basal ganglia
      contributions to sensory timing. Chronic-stage lesion patients and healthy
      controls listened to pure-tone sequences differing exclusively in temporal
      regularity. Event-related potentials (ERPs) indicate a selective indifference
      against this manipulation in patients, attributable to the striatal part of the
      basal ganglia on the basis of a lesion-mapping approach. These findings provide
      evidence for a crucial contribution of the basal ganglia to basic sensory
      functioning. 

PMID- 26298501
TI  - 2-(3'-Indolyl)-N-arylthiazole-4-carboxamides: Synthesis and evaluation of
      antibacterial and anticancer activities.
AB  - A new series of 2-(3'-indolyl)-N-arylthiazole-4-carboxamides 17a-p has been
      designed and synthesized. Initial reaction of readily available thioamides 15
      with bromopyruvic acid under refluxing conditions produced different thiazole
      carboxylic acids 16 which upon coupling with arylamines by using EDCI.HCl and
      HOBt afforded diverse arylthiazole-4-carboxamides 17a-p in 78-87% yields.
      Antibacterial activity evaluation against Gram-positive and Gram-negative
      bacterial strains led to compounds 17i-k and 17o as potent and selectively (Gram
      negative) antibacterial agents. The cytotoxicity of thiazole carboxamides 17a-p
      was also evaluated on a panel of human cancer cell lines. Among the tested
      derivatives, compounds 17i (IC50=8.64MUM; HEK293T) and 17l (IC50=3.41MUM; HeLa)
      were identified as the most potent analogues of the series. Preliminary mechanism
      of action studies of thiazole carboxamide 17i suggested that its cytotoxicity
      against HeLa cells involves the induction of cell death by apoptosis. 

PMID- 26298503
TI  - Differences in fMRI intersubject correlation while viewing unedited and edited
      videos of dance performance.
AB  - Intersubject correlation (ISC) analysis of functional magnetic resonance imaging
      (fMRI) data provides insight into how continuous streams of sensory stimulation
      are processed by groups of observers. Although edited movies are frequently used
      as stimuli in ISC studies, there has been little direct examination of the effect
      of edits on the resulting ISC maps. In this study we showed 16 observers two
      audiovisual movie versions of the same dance. In one experimental condition there
      was a continuous view from a single camera (Unedited condition) and in the other
      condition there were views from different cameras (Edited condition) that
      provided close up views of the feet or face and upper body. We computed ISC maps
      for each condition, as well as created a map that showed the difference between
      the conditions. The results from the Unedited and Edited maps largely overlapped
      in the occipital and temporal cortices, although more voxels were found for the
      Edited map. The difference map revealed greater ISC for the Edited condition in
      the Postcentral Gyrus, Lingual Gyrus, Precentral Gyrus and Medial Frontal Gyrus,
      while the Unedited condition showed greater ISC in only the Superior Temporal
      Gyrus. These findings suggest that the visual changes associated with editing
      provide a source of correlation in maps obtained from edited film, and highlight
      the utility of using maps to evaluate the difference in ISC between conditions. 

PMID- 26298504
TI  - Apraxia and spatial inattention dissociate in left hemisphere stroke.
AB  - Theories of lateralized cognitive functions propose a dominance of the left
      hemisphere for motor control and of the right hemisphere for spatial attention.
      Accordingly, spatial attention deficits (e.g., neglect) are more frequently
      observed after right-hemispheric stroke, whereas apraxia is a common consequence
      of left-hemispheric stroke. Clinical reports of spatial attentional deficits
      after left hemisphere (LH) stroke also exist, but are often neglected. By
      applying parallel analysis (PA) and voxel-based lesion-symptom mapping (VLSM) to
      data from a comprehensive neuropsychological assessment of 74 LH stroke patients,
      we here systematically investigate the relationship between spatial inattention
      and apraxia and their neural bases. PA revealed that apraxic (and language
      comprehension) deficits loaded on one common component, while deficits in
      attention tests were explained by another independent component. Statistical
      lesion analyses with the individual component scores showed that apraxic (and
      language comprehension) deficits were significantly associated with lesions of
      the left superior longitudinal fascicle (SLF). Data suggest that in LH stroke
      spatial attention deficits dissociate from apraxic (and language comprehension)
      deficits. These findings contribute to models of lateralised cognitive functions
      in the human brain. Moreover, our findings strongly suggest that LH stroke
      patients should be assessed systematically for spatial attention deficits so that
      these can be included in their rehabilitation regime. 

PMID- 26298506
TI  - Association between variable number of tandem repeats (VNTR) polymorphism in the
      promoter region of monoamine oxidase A (MAOA) gene and susceptibility to heroin
      dependence.

PMID- 26298505
TI  - Physicians' opinions following pharmacogenetic testing for psychotropic
      medication.
AB  - Pharmacogenetics seeks to improve patient drug response and decrease side effects
      by personalizing prescriptions using genetic information. Since 2012, by one
      estimate, the number of patients who have had pharmacogenetic testing has doubled
      and this number is expected to double again by 2015. Given the increasing
      evidence for genetic influences on treatment response, we deemed it important to
      study physicians' opinions of pharmacogenetic testing. Surveys were completed by
      168 Canadian physicians who had ordered at least one pharmacogenetic test (in
      particular for CYP2D6 or CYP2C19) for the prescription of psychiatric medication.
      Our results indicated that 80% of respondents believe genetic testing would
      become common standard in psychiatric drug treatment and 76% of respondents
      reported satisfactory or higher than satisfactory understanding of the
      pharmacogenetic report provided. Significantly more male physicians believed they
      had a higher understanding of the pharmacogenetic report compared to female
      physicians. To our knowledge, this is the only study that has assessed
      physicians' opinions of pharmacogenetic testing for psychotropic medication after
      they had received a pharmacogenetic report. Our results demonstrate a positive
      opinion of physicians on pharmacogenetics and indicate great potential for future
      clinical application. 

PMID- 26298507
TI  - A review of Neospora caninum in water buffalo (Bubalus bubalis).
AB  - A number of countries in the world have reported infections with Neospora caninum
      in water buffalo (Bubalus bubalis), from Africa to Asia, Europe and South America
      and recently Australia. In general, clinical manifestations (such as abortion)
      seem rare, which has raised the prospect that buffalo may be inherently resistant
      to clinical effects of N. caninum infection. Worldwide, the seroprevalence of N.
      caninum infection (as a measure of exposure determined by the detection of
      antibody) in buffalo is high, at approximately 48%. This reported seroprevalence
      is three or four times higher than that reported from the world's cattle
      populations, which have collective seroprevalence rates of 16.1% for dairy cattle
      and 11.5% for beef cattle. However, there is a lack of standardisation in
      seroprevalence studies and some studies may well under-estimate the true level of
      infection. Epidemiologic evidence supports post-natal transmission, and in utero
      transmission has also been demonstrated. The causes for water buffalo to have
      markedly higher seroprevalence but apparently lower neosporosis abortion rates
      than cattle warrant further investigation. 

PMID- 26298508
TI  - Bovine and ovine rumen fluke in Ireland-Prevalence, risk factors and species
      identity based on passive veterinary surveillance and abattoir findings.
AB  - The prevalence of rumen fluke, the incidence of clinical paramphistomosis and the
      trematode's species identity were studied in cattle and sheep in the Republic of
      Ireland using passive veterinary surveillance (faecal examination and necropsy
      results; 2010-2013) and abattoir data. Based on faecal examination, the
      prevalence of rumen fluke was higher in cattle than in sheep. Rumen fluke
      prevalence in cattle and sheep fluctuated over the year and in most years (2011
      2013), prevalence was higher in winter (December-February) than in summer (June
      August). For 3 of 4 years studied, there was no correlation between monthly
      prevalence of rumen fluke and prevalence of liver fluke as estimated by faecal
      examination. At sample level, joint occurrence of rumen fluke and liver fluke was
      1.1-2.0 times more common than would be expected under the assumption of
      independence. Based on necropsy data, a spike in deaths attributed to
      paramphistomosis was observed in 2012, when rainfall was unusually high. This
      spike in mortality was not accompanied by a spike in faecal prevalence,
      emphasizing that the incidence of disease, which is due to high burdens of
      juvenile rumen fluke in the gut, is not correlated with prevalence of infection,
      which is measured by faecal examination and reflects presence of adult fluke in
      the rumen. At slaughter, 52% of 518 cattle from 101 herds were positive for rumen
      fluke, compared to 14% of 158 sheep. Prevalence in cattle was higher than
      reported in most studies from mainland Europe and varied by animal category, age,
      sex, abattoir visit and location (county) of farm from which the animal was
      submitted for slaughter, but in multivariate analysis, only sampling month and
      county were significantly associated with detection of rumen fluke. The identity
      of rumen fluke in cattle and sheep was confirmed as Calicophoron daubneyi.
      Although C. daubneyi is thought to share an intermediate host snail with Fasciola
      hepatica, the differences in prevalence between host species and over time
      suggest that the epidemiology of C. daubneyi is distinct from that of F.
      hepatica. Further studies of the C. daubneyi life-cycle in ruminant hosts,
      intermediate snail hosts and the environment will be needed to gain a better
      understanding of modes of transmission and options for control of rumen fluke
      infection and disease. 

PMID- 26298509
TI  - Echinococcus multilocularis: Epidemiology, surveillance and state-of-the-art
      diagnostics from a veterinary public health perspective.
AB  - Alveolar echinococcosis (AE), caused by the larval (metacestode) stage of
      Echinococcus multilocularis, is considered one of the most serious parasitic
      zoonoses in Central and Eastern Europe and is emerging also in large parts of
      Asia and in North America. The red fox represents the main definitive host of E.
      multilocularis in Europe, but the raccoon dog, the domestic dog and to a much
      lesser extent the domestic cat also represent potential definitive hosts. The
      natural intermediate hosts of E. multilocularis are mainly voles. The spectrum of
      accidental hosts is broad and includes many species of monkeys, pigs, dogs and
      humans which get infected by oral uptake of the viable eggs. Yet, human AE is a
      very rare disease in Europe; incidences have increased in recent years, while the
      infection is widely distributed in foxes with high prevalences reaching up to 70%
      in some areas. Generally, infected foxes represent a zoonotic risk, which may be
      particularly relevant in urban areas. Furthermore, there is concern that the risk
      for humans to acquire AE may rise due to the suspected geographical spread of the
      parasite as assessed by infections in its definitive hosts and the high
      prevalences in some regions. Monitoring and surveillance activities have
      therefore been initiated in a few European countries. Several diagnostic
      strategies have been developed and validated in recent years, applying classical
      worm detection by microscopy, but also immunological (ELISA for coproantigen
      detection) and molecular tests (copro-DNA detection by PCR). However, there is an
      urgent need for defining minimal requirements and harmonised approaches for these
      activities to allow for a reliable assessment of the epidemiological situation in
      Europe and comparable results from different countries. 

PMID- 26298510
TI  - Molecular characterization of bot flies, Oestrus spp., (Diptera, Oestridae), from
      domestic and wild Bovidae hosts.
AB  - The identification of Oestrus spp. larvae from Bovidae hosts is a difficult task
      due to the great morphological similarity between species. The lack of
      unambiguous identification criteria could have also serious epidemiological
      implications since domestic and wild hosts are sympatric in many natural areas.
      In order to accurately identify the Oestrus parasitizing hosts, we characterized
      two different genetic markers, 28S (rRNA) and COI, in larvae collected from
      domestic sheep and goats, European mouflon and Iberian ibex. Our sequence
      analyses demonstrate that all samples, except those from Iberian ibex, greatly
      resembles O. ovis and so we conclude that the species parasitizing this ibex is
      not O. ovis. Further studies will be needed to confirm whether it is in fact O.
      caucasicus, as previously suggested, or even a new species. 

PMID- 26298511
TI  - All ecosystems potentially host electrogenic bacteria.
AB  - Instead of requiring metal catalysts, MFCs utilize bacteria that oxidize organic
      matter and either transfer electrons to the anode or take electrons from the
      cathode. These devices are thus based on a wide microbial diversity that can
      convert a large array of organic matter components into sustainable and renewable
      energy. A wide variety of explored environments were found to host electrogenic
      bacteria, including extreme environments. In the present review, we describe how
      different ecosystems host electrogenic bacteria, as well as the physicochemical,
      electrochemical and biological parameters that control the currents from MFCs. We
      also report how using new molecular techniques allowed characterization of
      electrochemical biofilms and identification of potentially new electrogenic
      species. Finally we discuss these findings in the context of future research
      directions. 

PMID- 26298512
TI  - Palmarosa [Cymbopogon martinii (Roxb.) Wats.] as a putative crop for
      phytoremediation, in tannery sludge polluted soil.
AB  - A field experiment using tannery sludge as a soil amendment material and
      palmarosa (Cymbopogon martinii) as a potential phytostabilizer was conducted to
      investigate their synergistic effect in relation to the improvement in soil
      quality/property. Three consecutive harvests of two cultivars of palmarosa-PRC-1
      and Trishna, were examined to find out the influence of different tannery sludge
      doses on their herb, dry matter, essential oil yield and heavy metal
      accumulation. Soil fertility parameters (N, P, K, Organic carbon) were markedly
      affected by different doses of sludge. Enhanced soil nitrogen was positively
      correlated with herb yield (0.719*) and plant height (0.797*). The highest dose
      of tannery sludge (100 t ha(-1)) exhibited best performance than other treatments
      with respect to herb, dry matter and oil yield in all three harvests. Trishna was
      found to be superior to PRC-1 in relation to same studied traits. Quality of oil
      varied, but was insignificant statistically. Uptake of heavy metals followed same
      order (Cr>Ni>Pb>Cd) in roots and shoots. Translocation factor <1 for all trace
      elements and Bioconcentration factor >1 was observed in case of all heavy metals.
      Overall, tannery sludge enhanced the productivity of crop and metal accumulation
      occurred in roots with a meager translocation to shoots, hence it can be used as
      a phytostabiliser. The major advantage of taking palmarosa in metal polluted soil
      is that unlike food and agricultural crops, the product (essential oil) is
      extracted by hydro-distillation and there is no chance of oil contamination, thus
      is commercially acceptable.

PMID- 26298513
TI  - Assessing foods offered in the Food Distribution Program on Indian Reservations
      (FDPIR) using the Healthy Eating Index 2010.
AB  - OBJECTIVE: To assess the nutritional quality of food packages offered in the Food
      Distribution Program on Indian Reservations (FDPIR) using the Healthy Eating
      Index 2010 (HEI-2010). DESIGN: Data were collected from the list of the food
      products provided by the US Department of Agriculture's Food and Nutrition
      Handbook 501 for FDPIR. Nutritional quality was measured through a cross
      sectional analysis of five randomly selected food packages offered through FDPIR.
      HEI-2010 component and total scores were calculated for each food package. ANOVA
      and t tests assessed significant differences between food packages and HEI-2010
      maximum scores, respectively. SETTING: This study took place in the USA.
      SUBJECTS: Study units included food products offered through FDPIR. RESULTS: The
      mean total HEI-2010 score for the combined FDPIR food packages was significantly
      lower than the total HEI-2010 maximum score of 100 (66.38 (sd 11.60); P<0.01).
      Mean scores for total fruit (3.52 (sd 0.73); P<0.05), total vegetables (2.58 (sd
      0.15); P<0.001), greens and beans (0.92 (sd 1.00); P<0.001), dairy (5.12 (sd
      0.63); P<0.001), total protein foods (4.14 (sd 0.56); P<0.05) and refined grains
      (3.04 (sd 2.90); P<0.001) were all significantly lower than the maximum values.
      CONCLUSIONS: The FDPIR food package HEI-2010 score was notably higher than other
      federal food assistance and nutrition programmes. Study findings highlight
      opportunities for the FDPIR to modify its offerings to best support lifestyles
      towards prevention of diet-related chronic disease.

PMID- 26298514
TI  - Rationale, Design, and Methods for Process Evaluation in the Childhood Obesity
      Research Demonstration Project.
AB  - OBJECTIVE: The cross-site process evaluation plan for the Childhood Obesity
      Research Demonstration (CORD) project is described here. DESIGN: The CORD project
      comprises 3 unique demonstration projects designed to integrate multi-level,
      multi-setting health care and public health interventions over a 4-year funding
      period. SETTING: Three different communities in California, Massachusetts, and
      Texas. PARTICIPANTS: All CORD demonstration projects targeted 2-12-year-old
      children whose families are eligible for benefits under Title XXI (CHIP) or Title
      XIX (Medicaid). INTERVENTION(S): The CORD projects were developed independently
      and consisted of evidence-based interventions that aim to prevent childhood
      obesity. The interventions promote healthy behaviors in children by applying
      strategies in 4 key settings (primary care clinics, early care and education
      centers, public schools, and community institutions). MAIN OUTCOME MEASURE(S):
      The CORD process evaluation outlined 3 main outcome measures: reach, dose, and
      fidelity, on 2 levels (researcher to provider, and provider to participant).
      ANALYSIS: The plan described here provides insight into the complex nature of
      process evaluation for consortia of independently designed multi-level, multi
      setting intervention studies. The process evaluation results will provide
      contextual information about intervention implementation and delivery with which
      to interpret other aspects of the program.

PMID- 26298515
TI  - Surface engineering of lentiviral vectors for gene transfer into gene therapy
      target cells.
AB  - Since they allow gene integration into their host genome, lentiviral vectors
      (LVs) have strong therapeutic potentials, as emphasized by recent clinical
      trials. The surface-display of the pantropic vesicular stomatitis virus G
      glycoprotein (VSV-G) on LVs resulted in powerful tools for fundamental and
      clinical research. However, improved LVs are required either to genetically
      modify cell types not permissive to classical VSV-G-LVs or to restrict entry to
      specific cell types. Incorporation of heterologous viral glycoproteins (gps) on
      LVs often require modification of their cytoplasmic tails and ligands can be
      inserted into their ectodomain to target LVs to specific receptors. Recently,
      measles virus (MV) gps have been identified as strong candidates for LV
      retargeting to multiple cell types, with the potential to evolve toward clinical
      applications. 

PMID- 26298516
TI  - CAV-2--why a canine virus is a neurobiologist's best friend.
AB  - Canine adenovirus type 2 (CAV-2) vectors are powerful tools for fundamental and
      applied neurobiology due to their negligible immunogenicity, preferential
      transduction of neurons, widespread distribution via axonal transport, and
      duration of expression in the mammalian brain. CAV-2 vectors are internalized in
      neurons by the selective use of coxsackievirus and adenovirus receptor (CAR),
      which is located at the presynapse in neurons. Neuronal internalization and
      axonal transport is mediated by CAR, which potentiates vector biodistribution.
      The above characteristics, together with the ~30kb cloning capacity of helper
      dependent (HD) CAV-2 vectors, optimized CAV-2 vector creation, production and
      purification, is expanding the therapeutic and fundamental options for CNS gene
      transfer. 

PMID- 26298518
TI  - Differential induction of meristematic stem cells of Catharanthus roseus and
      their characterization.
AB  - Plant cell culture technology has been introduced for the mass production of the
      many useful components. A variety of plant-derived compounds is being used in
      various fields, such as pharmaceuticals, foods, and cosmetics. Plant cell
      cultures are believed to be derived from the dedifferentiation process. In the
      present study, an undifferentiated cambial meristematic cell (CMCs) of
      Catharanthus is isolated using histological and genetic methods, and compared
      with dedifferentiation-derived callus (DDCs) cultures. Furthermore, differential
      culture conditions for both DDCs- and CMCs-derived cell lines were established. A
      suitable media for the increased accumulation of terpenoid indole alkaloids
      (TIAs) was also standardized. Compared with DDCs, CMCs showed marked accumulation
      of TIAs in cell lines grown on media with 1.5 mg.mL(-1) of NAA and 0.5 mg.mL(-1)
      of kinetin. CMCs-derived cultures of Catharanthus, as a source of key anticancer
      drugs (viblastine and vincristine), would overcome the obstacles usually
      associated with the production of natural metabolites through the use of DDCs.
      Cell culture systems that are derived from CMCs may also provide a cost-effective
      and eco-friendly basis for the sustainable production of a number of important
      plant natural products.

PMID- 26298519
TI  - Alcohol consumption and the risk of cancer in Brazil: A study involving 203,506
      cancer patients.
AB  - This study aims to analyze the association between alcohol consumption and the
      risk of developing the most common types of cancer in the Brazilian population.
      It is a case-control study in which the most common types of cancer were
      considered as cases and non-melanoma skin cancers as controls. Data were
      routinely obtained by hospital-based cancer registrars. Individuals between 18
      and 100 years old, diagnosed between January 1, 2000 and December 31, 2009, with
      information regarding alcohol consumption, were included. The odds ratio (OR) for
      each type of cancer was calculated, adjusting for confounding variables. The
      etiologic fraction (EF) was calculated in cases with statistically significant
      results. The study included 203,506 individuals (110,550 women and 92,956 men),
      with an average age of 59 years. A statistically significant association was
      found between alcohol consumption and increased risk of cancers of the
      respiratory and digestive systems, prostate, and female breast. The association
      between alcohol consumption and cancers of the urinary tract, male genital
      organs, and other neoplasias was not statistically significant. Consumption of
      alcoholic beverages increased the risk of developing cancer of the nasal cavity,
      pyriform sinus, oral cavity, oropharynx, nasopharynx, larynx, hypopharynx, lung,
      esophagus, stomach, liver, pancreas, breast, prostate, colon and rectum, and anus
      and anal canal. 

PMID- 26298517
TI  - Gut microbiota and allogeneic transplantation.
AB  - The latest high-throughput sequencing technologies show that there are more than
      1000 types of microbiota in the human gut. These microbes are not only important
      to maintain human health, but also closely related to the occurrence and
      development of various diseases. With the development of transplantation
      technologies, allogeneic transplantation has become an effective therapy for a
      variety of end-stage diseases. However, complications after transplantation still
      restrict its further development. Post-transplantation complications are closely
      associated with a host's immune system. There is also an interaction between a
      person's gut microbiota and immune system. Recently, animal and human studies
      have shown that gut microbial populations and diversity are altered after
      allogeneic transplantations, such as liver transplantation (LT), small bowel
      transplantation (SBT), kidney transplantation (KT) and hematopoietic stem cell
      transplantation (HTCT). Moreover, when complications, such as infection,
      rejection and graft versus host disease (GVHD) occur, gut microbial populations
      and diversity present a significant dysbiosis. Several animal and clinical
      studies have demonstrated that taking probiotics and prebiotics can effectively
      regulate gut microbiota and reduce the incidence of complications after
      transplantation. However, the role of intestinal decontamination in allogeneic
      transplantation is controversial. This paper reviews gut microbial status after
      transplantation and its relationship with complications. The role of intervention
      methods, including antibiotics, probiotics and prebiotics, in complications after
      transplantation are also discussed. Further research in this new field needs to
      determine the definite relationship between gut microbial dysbiosis and
      complications after transplantation. Additionally, further research examining gut
      microbial intervention methods to ameliorate complications after transplantation
      is warranted. A better understanding of the relationship between gut microbiota
      and complications after allogeneic transplantation may make gut microbiota as a
      therapeutic target in the future. 

PMID- 26298520
TI  - Arthroscopic Shoulder Surgical Simulation Training Curriculum: Transfer
      Reliability and Maintenance of Skill Over Time.
AB  - BACKGROUND: Surgical education is evolving as work hour constraints limit the
      exposure of residents to the operating room. Potential consequences may include
      erosion of resident education and decreased quality of patient care. Surgical
      simulation training has become a focus of study in an effort to counter these
      challenges. Previous studies have validated the use of arthroscopic surgical
      simulation programs both in vitro and in vivo. However, no study has examined if
      the gains made by residents after a simulation program are retained after a
      period away from training. METHODS: In all, 17 orthopedic surgery residents were
      randomized into simulation or standard practice groups. All subjects were
      oriented to the arthroscopic simulator, a 14-point anatomic checklist, and
      Arthroscopic Surgery Skill Evaluation Tool (ASSET). The experimental group
      received 1 hour of simulation training whereas the control group had no
      additional training. All subjects performed a recorded, diagnostic arthroscopy
      intraoperatively. These videos were scored by 2 blinded, fellowship-trained
      orthopedic surgeons and outcome measures were compared within and between the
      groups. After 1 year in which neither group had exposure to surgical simulation
      training, all residents were retested intraoperatively and scored in the exact
      same fashion. Individual surgical case logs were reviewed and surgical case
      volume was documented. RESULTS: There was no difference between the 2 groups
      after initial simulation testing and there was no correlation between case volume
      and initial scores. After training, the simulation group improved as compared
      with baseline in mean ASSET (p = 0.023) and mean time to completion (p = 0.01).
      After 1 year, there was no difference between the groups in any outcome
      measurements. CONCLUSION: Although individual technical skills can be cultivated
      with surgical simulation training, these advancements can be lost without
      continued education. It is imperative that residency programs implement a
      simulation curriculum and continue to train throughout the academic year.

PMID- 26298521
TI  - Improved glycemic control with teneligliptin in patients with type 2 diabetes
      mellitus on hemodialysis: Evaluation by continuous glucose monitoring.
AB  - AIMS: Recent reports suggest that appropriate glycemic control without
      hypoglycemia could decrease mortality in patients with diabetes mellitus (DM) and
      end-stage renal disease (ESRD). However, an indication of oral anti-diabetic
      drugs is limited in this population. The aim of this study was to evaluate
      efficacy of teneligliptin, a novel DPP-4 inhibitor, by continuous glucose
      monitoring (CGM) in patients with type 2 DM (T2DM) on hemodialysis (HD). METHODS:
      This 4-week, open label, single arm, intervention trial included 10 diabetic
      patients undergoing HD and with glycated albumin (GA) level of >=18.3%.
      Teneligliptin treatment was administered on days with HD sessions (HD day) and on
      days without HD sessions (NHD day); blood glucose values were measured by CGM.
      The primary endpoint was improvement of glycemic control evaluated by area under
      the curve (AUC). As secondary endpoints, changes in GA, HbA1c and fasting plasma
      glucose (FPG) were evaluated. RESULTS: Teneligliptin improved blood glucose AUC
      on both HD days (p=0.004), and NHD days (p=0.004). This was accompanied by a
      significant reduction in GA, HbA1c, and FPG, without severe hypoglycemia.
      CONCLUSIONS: Teneligliptin is one of the useful options for glycemic control in
      T2DM patients undergoing HD.

PMID- 26298522
TI  - Novel fabrication of fluorescent silk utilized in biotechnological and medical
      applications.
AB  - Silk fibroin (SF) is a natural polymer widely used and studied for diverse
      applications in the biomedical field. Recently, genetically modified silks,
      particularly fluorescent SF fibers, were reported to have been produced from
      transgenic silkworms. However, they are currently limited to textile
      manufacturing. To expand the use of transgenic silkworms for biomedical
      applications, a solution form of fluorescent SF needed to be developed. Here, we
      describe a novel method of preparing a fluorescent SF solution and demonstrate
      long-term fluorescent function up to one year after subcutaneous insertion. We
      also show that fluorescent SF labeled p53 antibodies clearly identify HeLa cells,
      indicating the applicability of fluorescent SF to cancer detection and bio
      imaging. Furthermore, we demonstrate the intraoperative use of fluorescent SF in
      an animal model to detect a small esophageal perforation (0.5 mm). This study
      suggests how fluorescent SF biomaterials can be applied in biotechnology and
      clinical medicine. 

PMID- 26298524
TI  - Effect of Dietary Weight Loss on Menstrual Regularity in Obese Young Adult Women
      with Polycystic Ovary Syndrome.
AB  - STUDY OBJECTIVE: To investigate the effect of dietary weight loss on menstrual
      regularity in obese adolescent women with polycystic ovary syndrome (PCOS).
      DESIGN AND SETTING: A randomized controlled trial was held at the Faculty of
      Nursing, Mansoura University, and the Obesity Clinic of the Rheumatology
      Department at Mansoura University Hospitals between July 2011 and January 2013.
      PARTICIPANTS: Sixty adolescent women with PCOS, body mass index (BMI) greater
      than 30, and complaints of menstrual irregularities were included in this study.
      Enrolled women were divided equally and randomly into 2 groups: intervention and
      control groups. INTERVENTIONS: Women in the intervention group (n = 30) were
      subject to an intensive dietary educational program with instructions to follow a
      conventional energy restricted diet, whereas women in the control group were
      instructed to follow the same healthy diet of the first group without calorie
      restriction. MAIN OUTCOME MEASURES: Menstrual regularity, weight loss, the effect
      on waist circumference, and hirsutism score. RESULTS: The 2 groups were initially
      matched in average body weight, BMI, hirsutism score, and waist circumference.
      Six months later, there were significant decreases in all parameters in the
      weight reduction group. In addition, more menstrual episodes were recorded in the
      weight reduction compared with the control group (3.1 +/- 1.2 vs. 2.3 +/- 1.3; P
      = .010). Also, BMI, waist circumference, and hirsutism score were all
      significantly decreased at the end of the study. CONCLUSION: Dietary weight loss
      in adolescent women with PCOS resulted in significant improvement in menstrual
      regularity, BMI, waist circumference, and hirsutism score.

PMID- 26298525
TI  - Association of PDCD1 polymorphism to Systemic Lupus Erythematosus and Rheumatoid
      Arthritis susceptibility.
AB  - OBJECTIVE: This study aims to analyze the relationship of programmed cell death 1
      (PDCD1) gene polymorphism (PD1.3G/A - rs11568821) with features of systemic lupus
      erythematosus (SLE) and rheumatoid arthritis (RA) in a Southern Brazilian
      population. METHODS: Polymerase Chain Reaction-Restriction Fragment Length
      Polymorphism (PCR-RFLP) was performed in 95 SLE and 87 RA patients and 128
      control group individuals from Santa Catarina, Southern Brazil. The Hardy
      Weinberg Equilibrium (HWE) test, and odds ratio (OR) were analyzed, considering
      CI 95% and p<=0.05. RESULTS: The PD1.3A allele frequencies were 0.095 (SLE),
      0.115 (RA) and 0.078 (controls). The genotypes of the control group were in HWE,
      while those of SLE and RA patients were not. However, we found no association
      between PD1.3 polymorphism and the SLE or RA susceptibility, nor clinical or
      epidemiological data. CONCLUSION: There was no significant association between
      PD1.3 polymorphism and SLE or RA susceptibility in this Southern Brazilian
      population.

PMID- 26298523
TI  - High resolution and dynamic imaging of biopersistence and bioreactivity of extra
      and intracellular MWNTs exposed to microglial cells.
AB  - Multi-walled carbon nanotubes (MWNTs) are increasingly being developed both as
      neuro-therapeutic drug delivery systems to the brain and as neural scaffolds to
      drive tissue regeneration across lesion sites. MWNTs with different degrees of
      acid oxidation may have different bioreactivities and propensities to aggregate
      in the extracellular environment, and both individualised and aggregated MWNTs
      may be expected to be found in the brain. Before practical application, it is
      vital to understand how both aggregates and individual MWNTs will interact with
      local phagocytic immune cells, the microglia, and ultimately to determine their
      biopersistence in the brain. The processing of extra- and intracellular MWNTs
      (both pristine and when acid oxidised) by microglia was characterised across
      multiple length scales by correlating a range of dynamic, quantitative and multi
      scale techniques, including: UV-vis spectroscopy, light microscopy, focussed ion
      beam scanning electron microscopy and transmission electron microscopy. Dynamic,
      live cell imaging revealed the ability of microglia to break apart and
      internalise micron-sized extracellular agglomerates of acid oxidised MWNTs, but
      not pristine MWNTs. The total amount of MWNTs internalised by, or strongly bound
      to, microglia was quantified as a function of time. Neither the significant
      uptake of oxidised MWNTs, nor the incomplete uptake of pristine MWNTs affected
      microglial viability, pro-inflammatory cytokine release or nitric oxide
      production. However, after 24 h exposure to pristine MWNTs, a significant
      increase in the production of reactive oxygen species was observed. Small
      aggregates and individualised oxidised MWNTs were present in the cytoplasm and
      vesicles, including within multilaminar bodies, after 72 h. Some evidence of
      morphological damage to oxidised MWNT structure was observed including highly
      disordered graphitic structures, suggesting possible biodegradation. This work
      demonstrates the utility of dynamic, quantitative and multi-scale techniques in
      understanding the different cellular processing routes of functionalised
      nanomaterials. This correlative approach has wide implications for assessing the
      biopersistence of MWNT aggregates elsewhere in the body, in particular their
      interaction with macrophages in the lung. 

PMID- 26298529
TI  - Screening of multi-targeted natural compounds for receptor tyrosine kinases
      inhibitors and biological evaluation on cancer cell lines, in silico and in
      vitro.
AB  - Receptors for growth factors encompass within the superfamily of receptor
      tyrosine kinases and are known to regulate numerous biological processes
      including cellular growth, proliferation, metabolism, survival, cell
      differentiation and apoptosis. These receptors have recently caught the attention
      of the researchers as an attractive target to combat cancer owing to the evidence
      suggesting their over-expression in cancer cells. Therefore, we studied receptor
      based molecular docking of IR (PDB; 3ETA), IGF1R (PDB; 1K3A), EGFR (PDB; 1M17),
      VEGFIR (PDB; 3HNG), and VEGFIIR (PDB; 2OH4) against natural compounds. Further,
      in vitro investigation of the biological effect of lead molecules in an array of
      cancer cell lines was done. All selected natural compounds were docked with the X
      ray crystal structure of selected protein by employing GLIDE (Grid-based Ligand
      Docking with Energetics) Maestro 9.6. InterBioScreen natural compounds docked
      with each selected protein molecules by using GLIDE high throughput virtual
      screening. On the basis of Gscore, we select 20 compounds along with 68
      anticancer compounds for GLIDE extra precision molecular docking. It was
      discovered in this study that compound epigallocatechin gallate (EGCG) yielded
      magnificent Gscore with IGF1R (PDB; 1K3A) and VEGFIIR (PDB; 2OH4), and protein
      ligand interactions are chart out. Effect of EGCG on biological activity such as
      mRNA expression of selected protein, cell proliferation, oxidative stress, and
      cell migration was reported after the 48 h treatments in cancer cell lines. The
      RT-PCR densitometric bands analysis showed that compound EGCG reduced the mRNA
      expression of IGF1R, VEGFIIR, and mTOR at 80 MUM concentration. Moreover, EGCG
      significantly reduced cell proliferation and ROS generation after 48 h
      treatments. Our result also indicated a reduction in the potential for cell
      migration that might show in vivo anti-metastasis activity of EGCG. 

PMID- 26298531
TI  - Pulmonary ventilation/perfusion single photon emission tomography--Initial
      experience of a Nuclear Medicine Department.
AB  - INTRODUCTION: Lung ventilation/perfusion scintigraphy with planar images (V/QS
      planar) is very useful for the diagnosis and follow-up of pulmonary
      thromboembolism (PTE). Acquiring tomographic images (V/QS-SPECT) is a recent
      development with potential to increase the technique's accuracy. The purpose of
      this work is to evaluate the added benefits of V/QS-SPECT studies as opposed to
      traditional planar imaging. PATIENTS AND METHODS: We prospectively revised 53
      V/QS-planar and V/QS-SPECT exams, performed according to the European Association
      of Nuclear Medicine guidelines. We evaluated the exams independently, by
      consensus of two Nuclear Medicine physicians. For both methods, we gave each lung
      a score expressing the dimension and extension of perfusion defects with normal
      ventilation. For each lung, we compared the scores with the paired Wilcoxon test,
      estimating the 95% confidence interval (95 CI) for the respective difference.
      RESULTS: We performed V/QS-SPECT exams without technical difficulties. The paired
      Wilcoxon test estimated the score difference to be -0.75 (95 CI of -1.0 to -0.5;
      p-value=9.6 * 10(-7)), expressing a statistically significant difference of about
      1 subsegmental defect between both methods, with V/QS-SPECT detecting more
      defects. DISCUSSION: The results demonstrate that V/QS-SPECT identifies a
      slightly larger number of perfusion defects than V/QS-planar, suggesting a higher
      sensitivity of this technique. However, more studies are necessary to evaluate
      the clinical meaning of this fact. CONCLUSION: V/QS-SPECT demonstrates a higher
      capability to identify perfusion defects. This method looks promising, allowing
      for a greater role of this exam in pulmonary thromboembolism diagnosis and follow
      up.

PMID- 26298530
TI  - Efficacy and safety of nab-paclitaxel combined with carboplatin in Chinese
      patients with melanoma.
AB  - This study aimed to evaluate the efficacy and safety of nab-paclitaxel combined
      with carboplatin in Chinese patients with melanoma. The treatment regimen
      consisted of nab-paclitaxel (100 mg/m(2)) and carboplatin (area under the curve =
      2) administered on days 1 and 8 every 21 days. All of the patients were evaluated
      on the basis of efficacy and safety in a two-cycle interval. Of the 45 patients,
      18 were chemotherapy naive and 27 were chemotherapy treated. Of these cases, 18
      manifested acral melanoma and 27 showed non-acral melanomas. Although
      chemotherapy-naive patients exhibited a higher response to the treatment, similar
      progression-free survival (PFS) and overall survival (OS) were detected in
      chemotherapy-naive and chemotherapy-treated patients. A higher response was
      observed in non-acral melanomas; however, similar PFS and OS occurred between
      acral and non-acral melanomas. The most common side effects were alopecia,
      myelosuppression, and gastrointestinal reaction. Nab-paclitaxel combined with
      carboplatin is a well-tolerated and effective regimen to treat Chinese patients
      with melanoma, including acral and non-acral melanomas. This treatment may be an
      alternative approach for Chinese patients with melanoma, especially those without
      the opportunity to undergo therapy with immune checkpoint inhibitors. 

PMID- 26298532
TI  - What's New at SIU Academy.

PMID- 26298533
TI  - Ultrasound in psoriatic arthritis. Can it facilitate a best routine practice in
      the diagnosis and management of psoriatic arthritis?
AB  - Important advances from both therapeutic and clinical assessment have recently
      been reported in psoriatic arthritis (PsA). Moreover, the constant challenge to
      provide a more comprehensive assessment of this heterogeneous disease results in
      a variety of clinical instruments that help the clinician for a global evaluation
      of both disease activity and responsiveness. The current European League Against
      Rheumatism (EULAR) recommendations on the use of imaging suggest the use of
      ultrasound (US) in chronic arthritis to increase the diagnostic accuracy and
      improvement of its management as compared to clinical examination alone. Although
      US findings are not firmly established in daily clinical practice, it
      demonstrated several positive aspects such as good sensitivity and specificity,
      acceptable reliability, and adequate sensitivity to change, especially in the
      peripheral PsA. Additionally, recent works introduced the role of US in the
      assessment of skin and nails opening interesting area of research. The aim of
      this paper is to describe the potential role of US in the assessment of PsA and
      to discuss the current evidence supporting its application in daily clinical
      practice. 

PMID- 26298534
TI  - The spectrum of posterior reversible encephalopathy in systemic lupus
      erythematosus.
AB  - Our aim was to compare our South African cohort of systemic lupus erythematosus
      (SLE) and posterior reversible encephalopathy syndrome (PRES) with other
      published series. We reviewed the records of 10 patients with SLE and PRES seen
      over a 10-year period and their demographic data, clinical manifestations,
      laboratory tests, imaging findings, and outcome were recorded. We identified 10
      females who included six Indians, three mixed ethnicity, and one African Black.
      Three patients had PRES at the onset of SLE. The most common manifestations at
      presentation were seizures (100 %), hypertension (80 %), and altered mental state
      (50 %). On neuroimaging, nine patients had bilateral involvement, and the
      occipital (90 %), parietal (90 %), and frontal lobes (50 %) were most commonly
      involved. The risk factors for PRES were disease activity (90 %), renal disease
      (80 %) and hypertension (80 %). Ninety percent of the patients were on
      immunosuppressive therapy. Immunosuppressive therapy was increased in six
      patients (60 %), continued in two and reduced in two patients after the diagnosis
      of PRES. Seven patients recovered completely and three patients died from co
      morbidities. A review of the larger case series of SLE and PRES showed that the
      presentation and neuroimaging findings were similar; most patients had active
      disease at the time of PRES and the majority of patients required intensification
      of immunosuppressive therapy. We have shown that the majority of patients with
      SLE have active disease at the time of PRES, and they require an increase in
      their immunosuppressive therapy.

PMID- 26298535
TI  - Prevalence and risk factors for intra-operative periprosthetic fractures in one
      thousand eight hundred and seventy two patients undergoing total hip
      arthroplasty: a cross-sectional study.
AB  - PURPOSE: The purpose of this study was to identify the frequency and type of
      intra-operative periprosthetic fractures and to describe risk factors in a single
      tertiary, public hospital, so that these events could be prevented, even among
      less experienced surgeons. METHODS: This is a cross-sectional study, based on
      medical records and imaging exams from the archives of a public, tertiary
      hospital, from April 1998 to October 2013. All consecutive patients submitted to
      total hip arthroplasty (THA) in the study period were evaluated, excluding
      unipolar or bipolar arthroplasty, surgery for the osteosynthesis of
      periprosthetic fractures, surgical procedure to clean infection site without
      component substitution and not arthroplastic surgery. Data were analyzed with chi
      squared test and multivariate Cox regression. RESULTS: In the study period, 1,872
      THA (1,728 patients) were performed and analyzed, with 144 bilateral cases. In
      173 cases, patients had undergone surgical procedures other than THA previously,
      and in only 260 the surgery consisted of revision THA. There were only two cases
      of resection THA. Among all patients 101 intra-operative periprosthetic fractures
      occurred. The univariate analysis revealed a significantly higher risk of intra
      operative fractures in female patients, aged more than 65 years, with indication
      of primary THA and the presence of a previous hip surgery. It indicated also that
      revision surgeries were associated with a 2.8-fold higher risk of intra-operative
      fracture, 2.18-fold risk in a previously operated hip and 3.9-fold in cases of
      resection THA or revision surgery in two stages. CONCLUSIONS: Intraoperative
      periprosthetic fracture is a rare event, and it is associated with revision type
      surgery and THA in a previously operated hip.

PMID- 26298536
TI  - Do manual cutting guides for total knee arthroplasty introduce systematic error?
AB  - INTRODUCTION: Conventional cutting guides in total knee arthroplasty can
      potentially cause unintentional deviation from the planned direction and depth of
      bone resection resulting in malaligned components. The purpose of this study was
      therefore to investigate the accuracy of bone cutting jigs for both the femur and
      tibia using imageless navigation. MATERIAL AND METHODS: A total of 125 patients
      with a mean age of 66.7 +/- 9.9 years underwent primary total knee arthroplasty
      with a Stryker TriathlonTM fixed bearing posterior cruciate retaining implant
      using imageless navigation. Coronal and sagittal position of the secured cutting
      jig was recorded and bone resection was checked with a rectangular probe attached
      to a navigation tracker. RESULTS: There were significant within group differences
      for the femoral sagittal cut (mean delta = 0.9 degrees  [31 %]; p = 0.00001),
      femoral depth medial compartment (mean delta = 0.5 mm [5 %]; p = 0.001), femoral
      depth lateral compartment (mean delta = 0.7 mm [7 %]; p = 0.00001), proximal
      tibial cut (mean delta = 0.3 mm [25 %]; p = 0.001), tibial depth medial
      compartment (mean delta = 0.6 mm [10 %]; p = 0.0001) and tibia depth lateral cut
      (mean delta = 0.4 mm [5 %]; p = 0.002). Deviation of more than 2 degrees  was
      observed for the distal cut in the sagittal plane in 17 % and in 9.6 % for the
      proximal tibial cut in the sagittal plane of all patients. CONCLUSION: The
      results of this study demonstrated significant differences between the dialed in
      cut and "actual" bone resection achieved for all planes for both the femur and
      tibia. The femur sagittal cut demonstrated a tendency for an extended cut and the
      tibia showed a tendency for varus.

PMID- 26298537
TI  - Preoperative radiologic characters to predict hemangiopericytoma from angiomatous
      meningioma.
AB  - BACKGROUND: Hemangiopericytoma is clinically difficult to be differentiated from
      angiomatous meningioma. We set out to determine if the preoperative MRI
      parameters can predict HPC from angiomatous meningioma. METHODS: A retrospective
      review of medical records was conducted for12 HPC patients and 17 angiomatous
      meningiomas. WHO-2007 grading was used for histopathological diagnosis.
      Preoperative radiologic parameters included tumor location, tumor size, tumor
      shape, T1-weighted signal, T2-weighted signal, T1-weighted Gd-enhanced image, ADC
      value, Flair signal, peritumoral edema (PTE), dural tail sign (DTS), vessel voids
      sign, arachnoid layer on T2-weighted MRI, tumor hemorrhage and necrosis were
      analyzed. Univariate analyses were conducted to examine the association between
      radiological or clinical and histopathological features. Binary logistic
      regression model was used to evaluate if the parameters predict the occurrence of
      HPC. RESULTS: Five parameters, included age, gender, ADC value, necrosis and T1
      enhancement was found significantly different between two types after univariate
      analyses. Binary logistic regression model demonstrated ADC value was the sole
      independent predictor of HPC (p=0.039, OR: 14.5, CI-3.7-38.6). CONCLUSIONS: ADC
      value may be used as a simple and useful optional tool in differentiating primary
      intracranial HPC from angiomatous meningioma. The combination of ADC value with
      the data acquired from pre and post-contrast MR scans may further help improve
      the reliability in the differential diagnosis.

PMID- 26298538
TI  - Multianalyte markers of schizophrenia and bipolar disorder: A preliminary study.
AB  - Previous studies have identified altered molecular profiles in blood samples from
      individuals with schizophrenia and with bipolar disorder using multianalyte
      immunoassay platforms but there has been little comparison of the two groups in
      the same investigation. A total of 337 participants including 146 with
      schizophrenia, 79 with bipolar disorder, and 112 non-psychiatric controls had a
      blood sample drawn from which 166 analytes were measured. The initial dataset was
      split; classification models were developed in a training dataset and their
      performance evaluated in a test dataset. Principal component analysis was used to
      generate factor scores that were then compared between the groups. In a training
      set, a total of 7 independent factors were generated using 29 markers that were
      both normally distributed and significantly associated with diagnosis. Many of
      these analytes are components of the immune system and involved in the
      inflammatory response to infectious agents and foreign antigens. Two of the seven
      principal component scores discriminated between individuals with schizophrenia
      and with bipolar disorder; additional factors distinguished individuals with
      either schizophrenia or bipolar disorder from control individuals, while two
      factors were not significantly different between any of the diagnostic groups. In
      a test dataset, the schizophrenia vs. control Receiver Operating Curve (ROC)
      analysis shows an overall accuracy of 77% for schizophrenia vs. bipolar disorder,
      84% for schizophrenia vs. controls, and 72% for bipolar disorder vs. CONTROLS: An
      increased understanding of the role of altered pathways in serious psychiatric
      disorders may lead to novel methods for disease diagnosis and therapy.

PMID- 26298539
TI  - Clozapine improves the orienting of attention in schizophrenia.
AB  - Attentional deficits are prominent in the cognitive profile of patients with
      schizophrenia. However, it remains unclear whether treatment with clozapine, an
      atypical antipsychotic and first-line intervention used to reduce positive and
      negative symptoms of psychosis, improves the attentional functions. We used the
      revised attention network test to measure alerting, orienting, and executive
      control of attention both pre- and post-treatment with clozapine in patients with
      schizophrenia (n=32) and compared performance to healthy controls (n=32). Results
      revealed that there were deficits in all three attentional functions pre
      treatment, and while clozapine improved the orienting function in patients with
      schizophrenia, there was no evidence for improvement in the alerting and
      executive control of attention. The enhancement of the orienting function by
      clozapine may increase the ability of patients with schizophrenia to orient
      towards objects and thoughts of interest. 

PMID- 26298540
TI  - Cytochrome P450 genotypes are not associated with refractoriness to antipsychotic
      treatment.
AB  - Evidence validating the influence of the cytochrome P450 (CYP) 2D6 and 2C19
      enzymes genetic polymorphisms in the response to antipsychotics is scarce. We
      examined the hypothesis that a higher prevalence of CYP2D6 and/or CYP2C19 ultra
      rapid metabolizers might be found among refractory schizophrenia patients. Three
      groups were studied: refractory and non-refractory schizophrenia patients, and
      healthy controls. Participants were genotyped for CYP2D6 and CYP2C19
      polymorphisms and classified in metabolic phenotypes. No between-group
      differences in the distribution of the phenotypes were found. Therefore, our
      findings do not support the CYPs 2D6 and 2C19 genotyping in the prediction of
      therapeutic response in schizophrenia. 

PMID- 26298541
TI  - Mindfulness improves psychological quality of life in community-based patients
      with severe mental health problems: A pilot randomized clinical trial.
AB  - OBJECTIVE: To examine the effectiveness of group mindfulness-based intervention
      (MBI) in patients diagnosed with severe mental illness. The primary outcome was
      health-related psychological quality of life. Secondary measures were
      environmental, social and physical health related quality of life, frequency and
      intensity of psychotic symptoms and daily-life mindfulness. METHOD: Forty-four
      patients from a public community rehabilitation center for people with severe
      mental illness were recruited, and randomly allocated to Integrated
      Rehabilitation Treatment (IRT) or IRT plus MBI. Measures included PANSS
      interview, WHOQOL-BREF, and Mindfulness Attention Awareness Scale. MBI comprised
      26 one-hour weekly sessions. Intention-to-treat analysis was used. RESULTS: One
      patient did not complete IRT+MBI and two did not complete IRT. At baseline there
      were no statistical group differences in demographic characteristics or primary
      and secondary outcomes. At post-treatment interaction between treatment and time
      in health-related psychological quality of life was statistically significant,
      and simple effect analysis showed significant differences for between and within
      subject factor in favor of MBI. Interaction was also significant in PANSS
      negative symptoms, simple effects showed a statistical trend in within subject
      factor. Time factor was significant in environmental and physical quality of
      life. CONCLUSIONS: Data suggest mindfulness added to IRT may enhance
      psychological quality of life in people with severe mental illness from a public
      community center. Results also suggest that mindfulness may impact frequency and
      intensity of negative symptoms.

PMID- 26298542
TI  - What can be more prognostic than the pTNM category assessed on radical cystectomy
      specimens?

PMID- 26298544
TI  - Sticky mittens, prickly Velcro, and infants' transition into independent
      reaching: Response to Williams, Corbetta, and Guan (2015).
AB  - Williams, Corbetta, and Guan (2015) report findings on the effects of active and
      passive motor training in three-month-old infants and argue that passive task
      exposure is sufficient to encourage future reaching behaviors. In this
      commentary, we relate these new findings to our body of published work using
      sticky mittens and describe important differences in the materials and procedures
      used. In particular, Williams et al. (2015) used modified sticky mittens that
      allowed infants' fingers to make direct contact with prickly Velcro on the toys,
      and they used a different training procedure that required infants to discover
      the hidden functionality of the sticky mittens by themselves. We argue that these
      differences explain the apparent conflicts between our prior work and the results
      reported by Williams et al. (2015). The Williams study presented infants with a
      learning context that was quite different from the one infants encountered in our
      research, and so it is not surprising that infants in their study showed such
      different patterns of behavior. 

PMID- 26298545
TI  - Pernicious anemia: Normal ferritin levels and possible hidden iron deficiency.

PMID- 26298543
TI  - Mantle cell lymphoma--a spectrum from indolent to aggressive disease.
AB  - Mantle cell lymphoma (MCL) is a distinctive lymphoma type generally characterized
      by the presence of CCND1 translocation and overexpression of cyclin D1. MCL
      usually presents with advanced stage and rapid clinical progression. The
      diagnosis is in most instances uncomplicated but cases with variant morphologies
      or immunophenotypes, especially cyclin D1-negative cases, may cause diagnostic
      difficulties. During the mantle cell lymphoma (MCL) session at the European
      Association of Haematopathology/Society for Hematopathology workshop 2014 held in
      Istanbul, Turkey, submitted cases illustrated interesting features such as
      unusual morphology or immunophenotypes. In several submitted cases of cyclin D1
      positive MCL, CCND1 rearrangement could not be detected by t(11;14)(q13;q32) dual
      color dual-fusion FISH but was suggested by CCND1 break-apart probes, and
      advantages and disadvantages of different FISH probes were highlighted. Three
      cyclin D1-negative MCL cases were submitted. These were identified by SOX11
      immunohistochemistry and found to carry CCND2 translocations and/or to express
      high levels of cyclin D2 mRNA. Features associated with aggressive clinical
      course were presented including high expression of p53 protein and MYC
      aberrations. The need to integrate histological, immunophenotypic, genetic, and
      clinical data to arrive at the correct diagnosis was emphasized. 

PMID- 26298546
TI  - A 25 years-old woman with a postvaccine thalamic pseudotumoral lesion.

PMID- 26298548
TI  - Accommodation insufficiency as the first sign of Guillain-Barre syndrome.

PMID- 26298547
TI  - Cripto-1 in TNBC.

PMID- 26298549
TI  - Unusual Cyclodextrin Derivatives as a New Avenue to Modulate Self- and Metal
      Induced Abeta Aggregation.
AB  - Mounting evidence suggests an important role of cyclodextrins in providing
      protection in neurodegenerative disorders. Metal dyshomeostasis is reported to be
      a pathogenic factor in neurodegeneration because it could be responsible for
      damage involving oxidative stress and protein aggregation. As such, metal ions
      represent an effective target. To improve the metal-binding ability of
      cyclodextrin, we synthesized three new 8-hydroxyquinoline-cyclodextrin conjugates
      with difunctionalized cyclodextrins. In particular, the 3-difunctionalized
      regioisomer represents the first example of cyclodextrin with two pendants at the
      secondary rim, resulting in a promising compound. The derivatives have
      significant antioxidant capacity and the powerful activity in inhibiting self
      induced amyloid-beta aggregation seems to be led by synergistic effects of both
      cyclodextrin and hydroxyquinoline. Moreover, the derivatives are also able to
      complex metal ions and to inhibit metal-induced protein aggregation. Therefore,
      these compounds could have potential as therapeutic agents in diseases related to
      protein aggregation and metal dyshomeostasis. 

PMID- 26298550
TI  - Factors prognostic for phonetic development after cleft palate repair.
AB  - BACKGROUND: Palatoplasty is aimed to achieve normal speech, improve food intake,
      and ensure successful maxillary growth. However, the velopharyngeal function is
      harder to control than other functions. Therefore, many studies on the prognostic
      factor of velopharyngeal insufficiency have been conducted. This study aimed to
      evaluate the relationships between speech outcomes and multimodality based on
      intraoral and preoperative three-dimensional computerized tomographic (CT)
      findings. METHODS: Among 73 children with cleft palate who underwent palatoplasty
      between April 2011 and August 2014 at Kyungpook National University Hospital
      (KNUH), 27 were retrospectively evaluated. The 27 cases were non-syndromic, for
      which successful speech evaluation was conducted by a single speech-language
      pathologist (Table 1). Successful speech evaluation was defined as performing the
      test three times in 6-month intervals. Three intraoral parameters were measured
      before and immediately after operation (Fig. 1). On axial- and coronal-view
      preoperative facial CT, 5 and 2 different parameters were analyzed, respectively
      (Figs. 2 and 3). Regression analysis (SPSS IBM 22.0) was used in the statistical
      analysis. RESULTS: Two-flap palatoplasty and Furlow's double opposing Z-plasty
      were performed in 15 and 12 patients, respectively. The operation was performed
      11 months after birth on average. Children with a higher palatal arch and wider
      maxillary tuberosity distance showed hypernasality (p < 0.05; Table 2).
      CONCLUSIONS: The useful prognostic factors of velopharyngeal function after
      palatoplasty were palate width and height, rather than initial diagnosis,
      treatment method, or palate length. Therefore, a more active intervention is
      needed, such as orthopedic appliance, posterior pharyngeal wall augmentation, or
      early speech training.

PMID- 26298551
TI  - Eye tracker based study: Perception of faces with a cleft lip and nose deformity.
AB  - AIM: Quantification of visual attention directed towards cleft stigmata and its
      impact on the perception of selected personality traits. METHODS: Forty observers
      were divided into two groups and their visual scan paths were recorded. Both
      groups observed a series of photographs displaying full frontal views of the
      faces of 18 adult patients with clefts, nine with residual cleft stigmata and
      nine with digitally-corrected stigmata (each patient only appeared once per
      series). Patients that appeared with residual stigmata in one series appeared
      digitally corrected in the other series and vice versa. Visual fixation times on
      the upper lip and nose were compared between the original and corrected
      photographs. Observers subsequently rated personality traits as perceived using
      visual analogue scales and the same photographs that they had observed in the
      series. RESULTS: In faces depicting cleft stigmata observers spent more time
      looking at the oronasal region of interest, followed by the eyes (39.6%; SD 5.0
      and 35.1%; SD 3.6, respectively, p = 0.0198). Observers spent more time looking
      at the cleft lip compared with the corrected lip (21.2%; SD 4.0 and 16.7%; SD
      5.0, respectively, p = 0.006). The differences between questionnaire scores for
      faces with cleft stigmata compared with faces with corrected stigmata for
      withdrawn-sociable, discontent-content, lazy-assiduous, unimaginative-creative,
      unlikeable-likeable, and the sum of individual personality traits were not
      significant. CONCLUSION: According to these findings, cleft lip and cleft nose
      have an attention-drawing potential with the cleft lip being the major attention
      drawing factor. These data do not provide supportive evidence for the notion
      reported in literature that patients with clefts are perceived as having negative
      personality traits.

PMID- 26298552
TI  - An initial meta-analysis of Acceptance and Commitment Therapy for treating
      substance use disorders.
AB  - BACKGROUND: In the past decade, multiple studies have examined the effectiveness
      of Acceptance and Commitment Therapy (ACT) for substance use disorders relative
      to other active treatments. The current meta-analysis examined the aggregate
      effect size when comparing ACT to other treatments (e.g., CBT, pharmacotherapy,
      12-step, treatment as usual) specifically on substance use outcomes. METHOD: A
      total of 10 randomized controlled trials were identified through systematic
      searches. RESULTS: A significant small to medium effect size was found favoring
      ACT relative to active treatment comparisons following treatment. Effect sizes
      were comparable across studies for smoking cessation (k=5) and for other drug use
      disorders (k=5). CONCLUSIONS: Based on these findings, ACT appears to be a
      promising intervention for substance use disorders. Limitations and future
      directions are discussed.

PMID- 26298553
TI  - Abstinence phenomena of chronic cannabis-addicts prospectively monitored during
      controlled inpatient detoxification (Part II): Psychiatric complaints and their
      relation to delta-9-tetrahydrocannabinol and its metabolites in serum.
AB  - OBJECTIVE: To investigate the impact of inpatient detoxification treatment on
      psychiatric symptoms of chronic cannabis addicts and to analyze the influence of
      serum cannabinoid levels on the severity of these symptoms. METHODS: Thirty five
      treatment-seeking, not active co-morbid chronic cannabis dependents (ICD-10) were
      studied on admission and on abstinence days 8 and 16, using several observational
      and self-report scales, such as Hamilton Depression Rating Scale (HAMD), Hamilton
      Anxiety Rating Scale (HAMA), Young Mania Rating Scale (YMRS) and Brief
      Psychiatric Rating Scale (BPRS), and the Symptom Checklist-90-Revised (SCL-90-R).
      Simultaneously obtained serum was analyzed with regard to levels of delta-9
      tetrahydrocannabinol (THC) and its main metabolites 11-hydroxy-delta-9
      tetrahydrocannabinol (THC-OH) and 11-nor-delta-9-tetrahydrocannabinol-9
      carboxylic acid (THC-COOH). RESULTS: At admission, nearly 90% of the patients
      were not, or only mildly, affected by depression, anxiety or manic symptoms. In
      contrast, patients' self-description indicated a strong psychiatric burden in
      approximately 60% of the cases. All patients improved significantly within 16
      days of the treatment. Effect sizes ranged from 0.7 to 1.4. (Cohen's d) for the
      respective scales. Serum THC-levels were positively associated with impairment of
      cognition in HAMA and motor retardation in BPRS. All other test results were not
      significantly related to the serum levels of the measured cannabinoids.
      DISCUSSION: Effects of the cannabis withdrawal syndrome and executive
      dysfunctions might explain the discrepancy between the observer ratings and self
      reported psychiatric burden. CONCLUSION: Inpatient cannabis detoxification
      treatment significantly improved psychiatric symptoms. Serum THC-levels were not
      associated with affective symptoms and anxiety but predicted cognitive impairment
      and motor retardation.

PMID- 26298554
TI  - Diagnostic performance of thyroid ultrasonography screening in pediatric patients
      with a hypothyroid, hyperthyroid or euthyroid goiter.
AB  - BACKGROUND: Goiter is frequently the first indicator of thyroid disease in
      children. OBJECTIVE: To evaluate the usefulness of ultrasonography (US) in the
      identification of potential malignant nodules and autoimmune thyroiditis in
      children with diffuse goiter. MATERIALS AND METHODS: This study consisted of 113
      patients <20 years with a diffuse goiter who underwent thyroid US. Parenchymal
      echogenicity and the presence of nodules and abnormal lymph nodes were evaluated
      on US; if a thyroid nodule was detected, its characteristics were analyzed. The
      diagnostic accuracy of the US findings in the diagnosis of autoimmune thyroid
      disease was assessed. RESULTS: Thyroid nodules were detected on US in 72 of the
      113 (63.7%) patients. Of these, 65 (90.3%) had probably benign nodules and 4
      (5.6%) patients had nodules suspicious of malignancy. The remaining had
      indeterminate nodules only. In one child with suspected malignant nodules,
      papillary thyroid cancer with coexisting autoimmune thyroiditis was confirmed.
      Hypoechogenicity was visualized in 23 (88.5%) patients with autoimmune
      thyroiditis and 12 (85.7%) with Graves disease. The sensitivity and specificity
      of micronodulation for autoimmune thyroiditis were 53.9% and 98.3%, respectively.
      CONCLUSION: Although the potential for malignant nodules is relatively low in
      children with diffuse goiter, US can detect focal thyroid disease and
      characterize the nodules. US thus plays a useful role in excluding autoimmune
      thyroiditis in this population.

PMID- 26298556
TI  - New environmentally-friendly antimicrobials and biocides from Andean and Mexican
      biodiversity.
AB  - Persistent application of pesticides often leads to accumulation in the
      environment and to the development of resistance in various organisms. These
      chemicals frequently degrade slowly and have the potential to bio-accumulate
      across the food chain and in top predators. Cancer and neuronal damage at genomic
      and proteomic levels have been linked to exposure to pesticides in humans. These
      negative effects encourage search for new sources of biopesticides that are more
      "environmentally-friendly" to the environment and human health. Many plant or
      fungal compounds have significant biological activity associated with the
      presence of secondary metabolites. Plant biotechnology and new molecular methods
      offer ways to understand regulation and to improve production of secondary
      metabolites of interest. Naturally occurring crop protection chemicals offer new
      approaches for pest management by providing new sources of biologically active
      natural products with biodegradability, low mammalian toxicity and
      environmentally-friendly qualities. Latin America is one of the world's most
      biodiverse regions and provide a previously unsuspected reservoir of new and
      potentially useful molecules. Phytochemicals from a number of families of plants
      and fungi from the southern Andes and from Mexico have now been evaluated. Andean
      basidiomycetes are also a great source of scientifically new compounds that are
      interesting and potentially useful. Use of biopesticides is an important
      component of integrated pest management (IPM) and can improve the risks and
      benefits of production of many crops all over the world. 

PMID- 26298555
TI  - A clinical decision rule for the use of plain radiography in children after acute
      wrist injury: development and external validation of the Amsterdam Pediatric
      Wrist Rules.
AB  - BACKGROUND: In most hospitals, children with acute wrist trauma are routinely
      referred for radiography. OBJECTIVE: To develop and validate a clinical decision
      rule to decide whether radiography in children with wrist trauma is required.
      MATERIALS AND METHODS: We prospectively developed and validated a clinical
      decision rule in two study populations. All children who presented in the
      emergency department of four hospitals with pain following wrist trauma were
      included and evaluated for 18 clinical variables. The outcome was a wrist
      fracture diagnosed by plain radiography. RESULTS: Included in the study were 787
      children. The prediction model consisted of six variables: age, swelling of the
      distal radius, visible deformation, distal radius tender to palpation, anatomical
      snuffbox tender to palpation, and painful or abnormal supination. The model
      showed an area under the receiver operator characteristics curve of 0.79 (95% CI:
      0.76-0.83). The sensitivity and specificity were 95.9% and 37.3%, respectively.
      The use of this model would have resulted in a 22% absolute reduction of
      radiographic examinations. In a validation study, 7/170 fractures (4.1%, 95% CI:
      1.7-8.3%) would have been missed using the decision model. CONCLUSION: The
      decision model may be a valuable tool to decide whether radiography in children
      after wrist trauma is required.

PMID- 26298557
TI  - Self-reported sunscreen use and urinary benzophenone-3 concentrations in the
      United States: NHANES 2003-2006 and 2009-2012.
AB  - BACKGROUND: Sunscreens protect against skin cancer and other harmful effects of
      solar ultraviolet radiation (UVR). Epidemiologic and public health surveys often
      rely on self-reported sunscreen use to estimate sun exposure and avoidance, but
      questions remain about the validity of self-reports. Benzophenone-3 (BP-3), a
      common sunscreen ingredient, can be detected in the urine. Prior studies suggest
      that BP-3 concentrations increase after application of sunscreen. OBJECTIVES: The
      goal of this study was to assess the validity of self-reported frequency of
      sunscreen use in relation to urinary BP-3 concentrations in a representative
      sample of the general US population, including in sub-groups defined by age, sex
      and race/ethnicity. METHODS: To assess the relationship between categorical self
      reported sunscreen use and creatinine-corrected urinary BP-3 concentrations, we
      conducted a linear regression adjusted for age, sex, race/ethnicity, six-month
      time period, body mass index, education, and sun avoidance behaviors. We tested
      for effect modification by age, sex, ethnicity and time period of measurement
      using multiplicative interaction terms and a F test. RESULTS: BP-3 was positively
      associated with self-reported frequency of sunscreen use across all ages, sexes,
      race/ethnicities, and time periods. Crude and multivariate adjusted models were
      all statistically significant. R-square was relatively low for all models,
      ranging from 0.15 to 0.43. CONCLUSIONS: Urinary BP-3 is positively associated
      with self-reported frequency of sunscreen use in the general US population, even
      in groups with overall low sunscreen use. These results suggest that self-report
      is a valid, although weak, way of assessing relative frequencies of sunscreen
      usage in a population-based study.

PMID- 26298559
TI  - 'Void existence' as against 'annihilation existence': Differentiating two
      qualities in primitive mental states.
AB  - This paper attempts to distil out a particular quality of psychic (non)existence,
      which I call here 'void existence', from the quality predominantly explored in
      the psychoanalytic discourse on primitive mental states, which I call
      'annihilation existence'. Achieving this phenomenological differentiation may
      make it easier to identify and work through extreme states in the analytic
      situation, when the patient is under the dominance of 'void existence'. I suggest
      that it is, as it were, a one-dimensional existence, in an infinite contour-less
      void, lacking any substantial internal object, lacking any substantial sense of
      psychic and/or somatic occurrences, and lacking any live representation of this
      very state of being. Hence, it lacks distress and anxiety, as well as calmness
      and peace. One might say that it is the inorganic within the organic; a quality
      of non-alive-ness within life. 'Annihilation existence' is existence in a two- or
      three-dimensional hollowed world, with flat and/or partial representations of
      self and object, which attracts acute distress and annihilation anxiety. It is a
      sort of existence on the brink of non-life, on the brink of the void; where a
      sense of catastrophic danger is brought on by the never-ending potentiality of
      the annihilation's realization. Both these psychic qualities can be encapsulated
      within neurotic and personality disorders, and the dominance of each can serve as
      defence against the dominance of the other. The theoretical discussion is
      supported by excerpts from an analysis. 

PMID- 26298558
TI  - Secondhand smoke in waterpipe tobacco venues in Istanbul, Moscow, and Cairo.
AB  - OBJECTIVE: The prevalence of waterpipe tobacco smoking has risen in recent
      decades. Controlled studies suggest that waterpipe secondhand smoke (SHS)
      contains similar or greater quantities of toxicants than cigarette SHS, which
      causes significant morbidity and mortality. Few studies have examined SHS from
      waterpipe tobacco in real-world settings. The purpose of this study was to
      quantify SHS exposure levels and describe the characteristics of waterpipe
      tobacco venues. METHODS: In 2012-2014, we conducted cross-sectional surveys of 46
      waterpipe tobacco venues (9 in Istanbul, 17 in Moscow, and 20 in Cairo). We
      administered venue questionnaires, conducted venue observations, and sampled
      indoor air particulate matter (PM2.5) (N=35), carbon monoxide (CO) (N=23),
      particle-bound polycyclic aromatic hydrocarbons (p-PAHs) (N=31), 4
      methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) (N=43), and air nicotine
      (N=46). RESULTS: Venue characteristics and SHS concentrations were highly
      variable within and between cities. Overall, we observed a mean (standard
      deviation (SD)) of 5 (5) waterpipe smokers and 5 (3) cigarette smokers per venue.
      The overall median (25th percentile, 75th percentile) of venue mean air
      concentrations was 136 (82, 213) ug/m(3) for PM2.5, 3.9 (1.7, 22) ppm for CO, 68
      (33, 121) ng/m(3) for p-PAHs, 1.0 (0.5, 1.9) ng/m(3) for NNK, and 5.3 (0.7, 14)
      ug/m(3) for nicotine. PM2.5, CO, and p-PAHs concentrations were generally higher
      in venues with more waterpipe smokers and cigarette smokers, although
      associations were not statistically significant. CONCLUSION: High concentrations
      of SHS constituents known to cause health effects indicate that indoor air
      quality in waterpipe tobacco venues may adversely affect the health of employees
      and customers.

PMID- 26298560
TI  - Gender differences in the accuracy of joint line tenderness for arthroscopically
      confirmed meniscal tears.
AB  - INTRODUCTION: The reliability of joint line tenderness was previously
      investigated among other clinical tests for the diagnosis of meniscal pathology
      with variable results. The aim of this study was to evaluate and compare the
      accuracy of joint line tenderness as a clinical diagnosing test for
      arthroscopically confirmed meniscal tears between males and females. MATERIALS
      AND METHODS: For the purpose of preoperative joint line tenderness accuracy
      calculations, this study included male and female groups of patients who have had
      knee arthroscopy following preoperative diagnosis of meniscal tear. Overall, 195
      patients were included in the study, 134 males and 61 females. The mean age was
      43.4 (13-76) years. RESULTS: In the male group, the diagnosis of meniscal tear by
      joint line tenderness was correct in 84 (62.7%) of 134 knees for the medial side
      and in 115 (85.8%) for the lateral side. In the female group, the diagnosis was
      correct in 35 (57.4%) of 61 knees for the medial side and in 57 (93.4%) for the
      lateral side. In order to refine the accuracy of medial joint line tenderness,
      the data were recalculated for patients with medial meniscal tears and no
      chondral lesion or cruciate ligament tears; however, the accuracy remained low.
      CONCLUSIONS: The physical finding of joint line tenderness of the knee as a test
      for lateral meniscal tear was found reliable in both males and females. For
      medial meniscal tears, the test had low reliability and thus less useful if used
      alone, in both genders.

PMID- 26298561
TI  - Platelet-rich plasma did not improve early healing of medial collateral ligament
      in rats.
AB  - BACKGROUND: The medial collateral ligament (MCL) is the most frequently injured
      ligament of the knee. Platelet-rich plasma (PRP) is a relatively new treatment
      option developed to enhance the healing response after injury to different tissue
      types. This study aimed at investigating whether the addition of PRP to MCL tears
      in rats would alter healing both biomechanically and histologically. METHODS:
      Bilateral full-thickness tears of the MCL were surgically induced in the knees of
      32 rats. Right ligament was saturated with PRP (n = 32, study group), and the
      left ligament was saturated with saline (n = 32, control group). The animals were
      killed 3 weeks later and the surgical sites were evaluated by gross inspection,
      biomechanically and histologically. RESULTS: There was no gross difference in the
      mass of granulation tissue, load to failure, stiffness and displacement between
      the study and control groups. Histological examination by means of maturity score
      revealed no significant differences between the study and control groups.
      CONCLUSION: The addition of PRP to a healing MCL did not improve any of the
      outcome measures in this model.

PMID- 26298562
TI  - Influence of posterior lateral femoral condyle geometry on patellar dislocation.
AB  - INTRODUCTION: Patellar instability is a condition with multifactorial aetiology,
      potentially involving soft tissue characteristics, the bony anatomy of the
      patella, femur and tibia, and alignment of the lower limb. The shape of the
      distal femur and patellofemoral joint has been frequently studied using plain
      orthogonal and skyline radiographs. We investigated a possible contribution of
      hypoplasia of the lateral femoral condyle in the axial plane to patellar
      instability. METHODS: The geometry of the distal femur and alignment of the lower
      limb on plain radiographs and MRI scans in 25 young adult patients with patellar
      instability was measured, and compared to a control group of 75 age-matched
      patients. Measurements were validated by intra-observer and inter-observer
      reliability studies, and multivariate analysis was used to compare the groups.
      Cases with and without high Beighton score or knee hyperextension were also
      compared. RESULTS: The anatomical posterior condylar angle, anterior condylar
      angle and sulcus angle on axial MRI scans showed insignificant differences
      between groups. The Blackburne-Peel ratio, anatomical femoro-tibial angle and
      femoral joint angle showed significant differences between groups, but not the
      tibial plateau angle. There was a significant correlation between posterior
      condylar angle and valgus knee alignment. In cases with joint hypermobility,
      femoral joint angle was significantly increased and posterior condylar angle was
      significantly decreased. CONCLUSIONS: Multiplanar hypoplasia of the lateral
      femoral condyle resulting in a valgus knee is a risk factor for patellar
      instability in young patients without osteoarthritis or joint hypermobility.
      Isolated posterior lateral condyle hypoplasia appears to be unrelated to patellar
      instability.

PMID- 26298563
TI  - Proximalize osteotomy of tibial tuberosity (POTT) as a treatment for stiffness
      secondary to patella baja in total knee arthroplasty (TKA).
AB  - INTRODUCTION: Stiffness after a total knee arthroplasty (TKA) is one of the most
      common post-operative complications. The purpose of this study is the evaluation
      of the effectiveness of TT proximalization osteotomy of improving a lack of
      flexion and secondary pain in patella baja (infera) post-TKA. MATERIALS AND
      METHODS: Between April 2007 and July 2012, TT proximalization osteotomy was
      performed on 21 patients. The average preoperative flexion was 70 degrees  (in a
      range of 60-80). Clinical pre- and post-operative evaluations were performed with
      Knee Society Score, Western Ontario and McMaster Universities Arthritis Index
      scales and a satisfaction survey. Modified Blackburn-Peel index and Portner angle
      were used to evaluate patellar height. RESULTS: After an average follow-up of 35
      months (range 18-48), an average flexion of 100 degrees  (range 90-100) and an
      overall satisfaction were obtained. Clinical scores improved significantly. The
      Blackburn-Peel index and Portner angle improved significantly from 0.3 (range 0.1
      0.5) to 0.4 (0.3-0.5) and from 9 (3-15) to 12 (9-18), respectively. Three
      patients showed no signs of osteotomy consolidation. However, this was not linked
      to a lack of extension or an increase in local pain. CONCLUSION: TT
      proximalization osteotomy provides satisfactory results in improving a lack of
      flexion and pain in patella baja post-TKR.

PMID- 26298564
TI  - Regulation and function of SIRT1 in rheumatoid arthritis synovial fibroblasts.
AB  - Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by
      inflammation and destruction of synovial joints. The function of sirtuin (SIRT)1
      in RA is inconclusive. In human synovial cells, SIRT1 was shown to promote
      cytokine production and apoptosis resistance. However, deletion of SIRT1
      aggravated inflammatory arthritis in mice and increased production of pro
      inflammatory cytokines in murine macrophages. In the current study, we
      investigated the regulation, expression, and function of SIRT1 in RA, in
      particular its role in adhesion and proliferation of human RA synovial
      fibroblasts (RASF). We found that expression of SIRT1 was increased in vivo in
      synovial tissues of RA smokers and in vitro by stimulation of RASF with TNFalpha,
      but decreased upon treatment with cigarette smoke extract. Synovial tissues of RA
      smokers showed higher leukocytic infiltration that positively correlated with
      enhanced levels of SIRT1. Global transcriptome analysis revealed that SIRT1
      modulates expression of genes involved in the regulation of inflammatory response
      and cell adhesion. In functional studies, silencing of SIRT1 reduced
      proliferation and leukocytic adhesion to RASF but showed inconsistent results in
      the regulation of adhesion to plastic. In conclusion, SIRT1 modulates the
      proliferative and potentially also adhesive properties of RASF and can therefore
      promote progression of RA. KEY MESSAGES: SIRT1 is upregulated by TNFalpha but
      decreased upon CSE treatment of RASF. Upregulation of SIRT1 in RA smokers
      correlates with increased leukocytic infiltration. SIRT1 modulates expression of
      genes regulating cell adhesion and inflammation. SIRT1 regulates proliferation of
      RASF.

PMID- 26298565
TI  - GUCY2D mutations in a Chinese cohort with autosomal dominant cone or cone-rod
      dystrophies.
AB  - BACKGROUND: To report the results of the GUCY2D gene mutation analysis in a
      cohort of Chinese patients with cone or cone-rod dystrophies (COD or CORD) and to
      describe the clinical features observed in patients with molecularly confirmed
      COD or CORD. METHODS: A total of 74 probands clinically diagnosed with COD or
      CORD were recruited for genetic analysis; these included 15 unrelated patients
      with a positive family history consistent with an autosomal dominant pattern of
      inheritance and 59 unrelated sporadic cases. All probands underwent ophthalmic
      examinations including best-corrected visual acuity, fundus examination, optical
      coherence tomography, and electroretinography. Genomic DNA was extracted from
      venous blood of all participants, and all coding exons and exon-intron boundaries
      of the GUCY2D gene were screened for mutations by PCR-based DNA sequencing.
      Restriction fragment length polymorphism analysis and allele-specific PCR
      analysis were used to validate the substitution in all available family members.
      RESULTS: Four different GUCY2D missense mutations--three affected codon 838 and
      one affected codon 849--were identified in nine unrelated probands. Mutation
      p.R838H was identified in four probands, while both mutations p.R838C and p.R838P
      were found in two unrelated patients, and mutation p.T849A was found in one
      proband. The GUCY2D mutations were found in 47% of the patients (7/15) with
      autosomal dominant cone dystrophy. Patients with mutation p.R838P presented a
      relatively severe clinical phenotype. CONCLUSION: The GUCY2D mutations were
      frequent in Chinese families with autosomal dominant cone or cone-rod
      dystrophies. All mutations were found in exon 13, which should be given priority
      during mutation screening analysis.

PMID- 26298566
TI  - Negotiating competing discourses in narratives of midwifery leadership in the
      English NHS.
AB  - OBJECTIVE: to explore midwifery leaders' narratives of identity, within the
      context of one region of England. DESIGN: a qualitative study using narrative
      identity theory. Data were collected using in-depth, loosely structured narrative
      interviews. SETTING: the study was undertaken in the Midlands region of England,
      in the context of a midwifery-specific leadership development programme.
      Participants were located in local NHS organisations and higher education
      institutions. PARTICIPANTS: the interviewees were midwives currently in one of a
      variety of formal leadership roles, who had recently completed a midwifery
      leadership development programme. Nine leaders were interviewed for the study.
      FINDINGS: two central themes emerged: 'I am still a midwife' showed interviewees'
      continued self-identification according to their professional identity, despite
      the majority no longer holding a clinical role; 'Between a rock and a hard place'
      showed the challenges of maintaining a professionally-based identity narrative in
      the face of group and organisational discourses. KEY CONCLUSIONS: among the
      midwifery leaders interviewed, narratives centred on a continued midwife self
      identification. However, participants faced a number of challenges in maintaining
      this narrative, within the context of wider professional group and organisational
      discourses. IMPLICATIONS FOR PRACTICE: midwifery leaders require the support of
      their professional group and organisational structures if they are to maintain a
      positive self- and social-identity.

PMID- 26298567
TI  - Antihypertensive Therapies and Cognitive Function: a Review.
AB  - Increasing life expectancy has made old age-related health problems like dementia
      and cognitive decline more prevalent, and these are rapidly becoming important
      causes of disability and poor quality of life, causing significant add-ons to
      health-care costs worldwide. Hypertension is the most important modifiable
      vascular risk factor for the development and progression of both cognitive
      decline and dementia. In many observational and randomized studies,
      antihypertensive therapies have been shown to be beneficial in slowing cognitive
      decline. However, due to observed discrepancies by these studies, there is a lack
      of consensus on the best antihypertensive strategy for the prevention or slowing
      of cognitive decline. It is also not clear whether the beneficial effect of
      antihypertensive therapy is due to the use of a specific class of agents or
      combination therapy. Thus, we present a comprehensive review of overall
      antihypertensive therapies and cognition and of the individual antihypertensive
      therapy classes with their specific protective mechanisms and available clinical
      evidence behind their effect on cognitive function.

PMID- 26298569
TI  - Diabetic kidney disease: what does the next era hold?

PMID- 26298568
TI  - Vitellogenin-RNAi and ovariectomy each increase lifespan, increase protein
      storage, and decrease feeding, but are not additive in grasshoppers.
AB  - Reduced reproduction has been shown to increase lifespan in many animals, yet the
      mechanisms behind this trade-off are unclear. We addressed this question by
      combining two distinct, direct means of life-extension via reduced reproduction,
      to test whether they were additive. In the lubber grasshopper, Romalea
      microptera, ovariectomized (OVX) individuals had a ~20% increase in lifespan and
      a doubling of storage relative to controls (Sham operated). Similarly, young
      female grasshoppers treated with RNAi against vitellogenin (the precursor to egg
      yolk protein) had increased fat body mass and halted ovarian growth. In this
      study, we compared VgRNAi to two control groups that do not reduce reproduction,
      namely buffer injection (Buffer) and injection with RNAi against a hexameric
      storage protein (Hex90RNAi). Each injection treatment was tested with and without
      ovariectomy. Hence, we tested feeding, storage, and lifespans in six groups: OVX
      and Buffer, OVX and Hex90RNAi, OVX and VgRNAi, Sham and Buffer, Sham and
      Hex90RNAi, and Sham and VgRNAi. Ovariectomized grasshoppers and VgRNAi
      grasshoppers each had similar reductions in feeding (~40%), increases in protein
      storage in the hemolymph (150-300%), and extensions in lifespan (13-21%).
      Ovariectomized grasshoppers had higher vitellogenin protein levels than did
      VgRNAi grasshoppers. Last but not least, when ovariectomy and VgRNAi were applied
      together, there was no greater effect on feeding, protein storage, or longevity.
      Hence, feeding regulation, and protein storage in insects, may be conserved
      components of life-extension via reduced reproduction.

PMID- 26298570
TI  - Mortality and metformin use in patients with advanced chronic kidney disease.

PMID- 26298571
TI  - Mortality and metformin use in patients with advanced chronic kidney disease-
      Authors' reply.

PMID- 26298572
TI  - Testosterone and cardiovascular risk.

PMID- 26298573
TI  - Country in Focus: economic transition and non-communicable diseases in Thailand.

PMID- 26298574
TI  - Sexual orientation disparities in physical health: age and gender effects in a
      population-based study.
AB  - BACKGROUND: Recent studies have identified substantial health disparities between
      lesbian, gay, and bisexual (LGB) individuals compared to heterosexuals. However,
      possible variation in sexual orientation health disparities by age and according
      to gender remains largely unexplored. PURPOSE: To examine physical health
      disparities between LGB and heterosexual individuals in a general population
      sample in Sweden, to explore potential age and gender differences in these
      disparities, and to test potential mechanisms underlying any observed
      disparities. METHOD: Between 2008 and 2013, 60,922 individuals (16-84 years of
      age) responded to nationwide population-based health surveys. In the sample, 430
      (0.7%) individuals self-identified as gay/lesbian and 757 (1.3%) self-identified
      as bisexual. Logistic and negative binomial regression analyses were used to
      explore health disparities based on sexual orientation. RESULTS: Overall, LGB
      individuals were more likely to report worse self-rated health as well as more
      physical health symptoms (e.g., pain, insomnia, dermatitis, tinnitus, intestinal
      problems) and conditions (e.g., diabetes, asthma, high blood pressure) compared
      to heterosexuals. However, these physical health disparities differed by age.
      Disparities were largest among adolescents and young adults and generally
      smallest in older age groups. Health behaviors and elevated reports of exposure
      to perceived discrimination, victimization, and threats of violence among sexual
      minorities partially explained the sexual orientation disparities in physical
      health. CONCLUSIONS: Age emerged as an important effect modifier of physical
      health disparities based on sexual orientation. Gender-specific findings suggest
      that sexual orientation disparities persist into adulthood for women but are
      gradually attenuated for older age groups; in contrast, for men, these
      disparities disappear starting with young adults. These results support a
      developmental model of minority stress and physical health among LGB individuals.

PMID- 26298575
TI  - Leishmania tarentolae secreting the sand fly salivary antigen PpSP15 confers
      protection against Leishmania major infection in a susceptible BALB/c mice model.
AB  - Cutaneous leishmaniasis is a zoonotic, vector-borne disease causing a major
      health problem in several countries. No vaccine is available and there are
      limitations associated with the current therapeutic regimens. Immune responses to
      sand fly saliva have been shown to protect against Leishmania infection. A
      cellular immune response to PpSP15, a protein from the sand fly Phlebotomus
      papatasi, was sufficient to control Leishmania major infection in mice. This work
      presents data supporting the vaccine potency of recombinant live non-pathogenic
      Leishmania (L.) tarentolae secreting PpSP15 in mice and its potential as a new
      vaccine strategy against L. major. We generated a recombinant L. tarentolae
      PpSP15 strain delivered in the presence of CpG ODN and evaluated its
      immunogenicity and protective immunity against L. major infection in BALB/c mice.
      In parallel, different vaccination modalities using PpSP15 as the target antigen
      were compared. Humoral and cellular immune responses were evaluated before and at
      three and eight weeks after challenge. Footpad swelling and parasite load were
      assessed at eight and eleven weeks post-challenge. Our results show that
      vaccination with L. tarentolae-PpSP15 in combination with CpG as a prime-boost
      modality confers strong protection against L. major infection that was superior
      to other vaccination modalities used in this study. This approach represents a
      novel and promising vaccination strategy against Old World cutaneous
      leishmaniasis. 

PMID- 26298576
TI  - Transcriptional regulation of T cell metabolism.
AB  - T cells express specific metabolic programs to promote diverse cellular
      differentiation states. The activation of naive T cells upregulates the
      expression of genes encoding components of the glycolysis, glutaminolysis, and
      lipid biosynthesis pathways to promote robust proliferation and effector T cell
      activity. In contrast, memory T cells downregulate these pathways and
      predominantly rely on catabolic pathways for long-term survival. Dynamic changes
      in the expression of the genes encoding components of metabolic pathways in part
      define which metabolic programs are utilized in diverse T cell states. The
      current data suggest that key transcription factors involved in T cell
      specialization decisions, including T-bet, Bcl-6, HIF1, IRF4 and Myc, link the
      selective programming of cellular metabolism with fate decisions. In this review,
      we will highlight the transcriptional regulatory events that define metabolic
      pathways involved in effector and memory T cell differentiation. 

PMID- 26298578
TI  - Discovery of Novel GSK-3beta Inhibitors Using Pharmacophore and Virtual Screening
      Studies.
AB  - Glycogen synthase kinase-3beta (GSK-3beta) is a kinase family enzyme and an
      emerged target for the treatment of various diseases. A total of 23 structurally
      diverse flavonoid inhibitors were used to generate pharmacophore models using
      HypoGen algorithm. The hypotheses Hypo1 was considered as a best model which
      consists of three features: one hydrophobic and two aromatic ring features. The
      Hypo1 pharmacophore model was employed as a query to screen NCI and natural
      compound databases to discover novel potential lead compounds. In addition,
      molecular docking studies were carried out with 596 compounds from screening
      studies. NSC230353, NSC66454, NSC159593, and NSC156759 from NCI database and
      STOCK1N-81808, ZINC02159818, ZINC04042470, and ZINC72326235 from natural compound
      database were identified as potential GSK-3beta inhibitors. 

PMID- 26298577
TI  - Hypoxia-inducible factors regulate T cell metabolism and function.
AB  - Resolution of infection requires the coordinated response of heterogeneous cell
      types to a range of physiological and pathological signals to regulate their
      proliferation, migration, differentiation, and effector functions. One mechanism
      by which immune cells integrate these signals is through modulating metabolic
      activity. A well-studied regulator of cellular metabolism is the hypoxia
      inducible factor (HIF) family, the highly conserved central regulators of
      adaptation to limiting oxygen tension. HIF's regulation of cellular metabolism
      and a variety of effector, signaling, and trafficking molecules has made these
      transcription factors a recent topic of interest in T cell biology. Low oxygen
      availability, or hypoxia, increases expression and stabilization of HIF in immune
      cells, activating molecular programs both unique and common among cell types,
      including glycolytic metabolism. Notably, numerous oxygen-independent signals,
      many of which are active in T cells, also result in enhanced HIF activity. Here,
      we discuss both oxygen-dependent and -independent regulation of HIF activity in T
      cells and the resulting impacts on metabolism, differentiation, function, and
      immunity. 

PMID- 26298579
TI  - Effects of Different Carbon Sources on Growth, Membrane Permeability, beta
      Sitosterol Consumption, Androstadienedione and Androstenedione Production by
      Mycobacterium neoaurum.
AB  - Effects of different carbon sources on growth, membrane permeability, beta
      sitosterol consumption, androstadienedione and androstenedione (AD(D)) production
      by Mycobacterium neoaurum were investigated. The results indicated that glucose
      was advantageous to the growth and resulted in the adverse effects on the
      phytosterols consumption and AD(D) production compared to the results of propanol
      and isopropanol as sole carbon source. The cell wall widths of 9.76 by propanol
      and 8.00 nm by isopropanol were 38.3 and 49.4 % thinner than that of 15.82 nm by
      glucose, respectively. The partition coefficient of the cell grown in propanol
      and isopropanol was 18.1 and 22.2, which were 7.23- and 9.09-fold higher than
      that of the cell grown in glucose. 

PMID- 26298580
TI  - PPDB: A Tool for Investigation of Plants Physiology Based on Gene Ontology.
AB  - Representing the way forward, from functional genomics and its ontology to
      functional understanding and physiological model, in a computationally tractable
      fashion is one of the ongoing challenges faced by computational biology. To
      tackle the standpoint, we herein feature the applications of contemporary
      database management to the development of PPDB, a searching and browsing tool for
      the Plants Physiology Database that is based upon the mining of a large amount of
      gene ontology data currently available. The working principles and search options
      associated with the PPDB are publicly available and freely accessible online (
      http://www.iitr.ac.in/ajayshiv/ ) through a user-friendly environment generated
      by means of Drupal-6.24. By knowing that genes are expressed in temporally and
      spatially characteristic patterns and that their functionally distinct products
      often reside in specific cellular compartments and may be part of one or more
      multicomponent complexes, this sort of work is intended to be relevant for
      investigating the functional relationships of gene products at a system level
      and, thus, helps us approach to the full physiology. 

PMID- 26298581
TI  - A Filter Feature Selection Method Based on MFA Score and Redundancy Excluding and
      It's Application to Tumor Gene Expression Data Analysis.
AB  - Feature selection techniques have been widely applied to tumor gene expression
      data analysis in recent years. A filter feature selection method named marginal
      Fisher analysis score (MFA score) which is based on graph embedding has been
      proposed, and it has been widely used mainly because it is superior to Fisher
      score. Considering the heavy redundancy in gene expression data, we proposed a
      new filter feature selection technique in this paper. It is named MFA score+ and
      is based on MFA score and redundancy excluding. We applied it to an artificial
      dataset and eight tumor gene expression datasets to select important features and
      then used support vector machine as the classifier to classify the samples.
      Compared with MFA score, t test and Fisher score, it achieved higher
      classification accuracy. 

PMID- 26298582
TI  - Computational Analysis and In silico Predictive Modeling for Inhibitors of PhoP
      Regulon in S. typhi on High-Throughput Screening Bioassay Dataset.
AB  - There is emergence of multidrug-resistant Salmonella enterica serotype typhi in
      pandemic proportions throughout the world, and therefore, there is a necessity to
      speed up the discovery of novel molecules having different modes of action and
      also less influenced by the resistance formation that would be used as drug for
      the treatment of salmonellosis particularly typhoid fever. The PhoP regulon is
      well studied and has now been shown to be a critical regulator of number of gene
      expressions which are required for intracellular survival of S. enterica and
      pathophysiology of disease like typhoid. The evident roles of two-component PhoP
      /PhoQ-regulated products in salmonella virulence have motivated attempts to
      target them therapeutically. Although the discovery process of biologically
      active compounds for the treatment of typhoid relies on hit-finding procedure,
      using high-throughput screening technology alone is very expensive, as well as
      time consuming when performed on large scales. With the recent advancement in
      combinatorial chemistry and contemporary technique for compounds synthesis, there
      are more and more compounds available which give ample growth of diverse compound
      library, but the time and endeavor required to screen these unfocused massive and
      diverse library have been slightly reduced in the past years. Hence, there is
      demand to improve the high-quality hits and success rate for high-throughput
      screening that required focused and biased compound library toward the particular
      target. Therefore, we still need an advantageous and expedient method to
      prioritize the molecules that will be utilized for biological screens, which
      saves time and is also inexpensive. In this concept, in silico methods like
      machine learning are widely applicable technique used to build computational
      model for high-throughput virtual screens to prioritize molecules for advance
      study. Furthermore, in computational analysis, we extended our study to identify
      the common enriched structural entities among the biologically active compound
      toward finding out the privileged scaffold. 

PMID- 26298583
TI  - Computational Analysis of the Domain Architecture and Substrate-Gating Mechanism
      of Prolyl Oligopeptidases from Shewanella woodyi and Identification of Probable
      Lead Molecules.
AB  - Prolyl oligopeptidases (POPs) are serine proteases found in prokaryotes and
      eukaryotes which hydrolyze the peptide bond containing proline. The current study
      focuses on the analysis of POP sequences, their distribution and domain
      architecture in Shewanella woodyi, a Gram-negative, luminous bacterium which
      causes celiac sprue and similar infections in marine organisms. The POP undergoes
      huge interdomain movement, which allows possible route for the entry of any
      substrate. Hence, it offers an opportunity to understand the mechanism of
      substrate gating by studying the domain architecture and possibility to identify
      a probable drug target. In the present study, the POP sequence was retrieved from
      GenBank database and the best homologous templates were identified by PSI-BLAST
      search. The three-dimensional structures of the closed and open forms of POP from
      S. woodyi, which are not available in native form, were generated by homology
      modeling. The ideal lead molecules were screened by computer-aided virtual
      screening, and the binding potential of the best leads toward the target was
      studied by molecular docking. The domain architecture of the POP revealed that it
      has a propeller domain consists of [Formula: see text]-sheets, surrounded by
      [Formula: see text]-helices and [Formula: see text] hydrolase domain with
      catalytic triad containing Ser-564, Asp-646 and His-681. The hypothetical models
      of open and closed POP showed backbone RMSD value of 0.56 and 0.65 A,
      respectively. Ramachandran plot of the open and closed POP conformations accounts
      for 99.4 and 98.7 % residues in the favoured region, respectively. Our study
      revealed that propeller domain comes as an insert between N-terminal and C
      terminal [Formula: see text] hydrolase domain. Molecular docking, drug likeness
      properties and ADME prediction suggested that KUC-103481N and Pramiracetum can be
      used as probable lead molecules toward the POP from S. woodyi. 

PMID- 26298584
TI  - Disassortative mixing patterns of drug-using and sex networks on HIV risk
      behaviour among young drug users in Yunnan, China.
AB  - OBJECTIVES: The dominant mode of HIV transmission in China has changed from
      injection drug use to sexual contact. The objectives of this study were to
      describe the disassortative and assortative mixing patterns of drug-using and sex
      networks among young drug users in China. STUDY DESIGN: Cross-sectional study.
      METHODS: Respondent-driven sampling (RDS) was used to recruit young drug users in
      an egocentric network study in Yunnan, China. Egos were categorized as having
      disassortative mixing network patterns if they reported both sex and drug-using
      networks. Egos who only had a sex network (no drug-using network), or only a drug
      using network (no sex network) were categorized as having assortative mixing
      network patterns. Multiple logistic regression was performed to analyze the
      relationships between disassortative patterns with risky sexual behaviour and
      drug-using practices. RESULTS: A total of 426 participants were recruited into
      the study. Two hundred forty-two egos reported disassortative mixing patterns and
      139 egos had assortative patterns. The RDS-adjusted proportion of having a
      disassortative pattern was 53.2%. Participants with disassortative patterns were
      more likely to engage in HIV risk behaviour compared to those with assortative
      patterns. Specifically, drug users with disassortative patterns reported more
      multiple sex partners (31.4% vs 19.6%), concurrent partnerships (52.1% vs 39.0%),
      non-regular sex partners (12.0% vs 4.3%), and sex partners who were IDUs (24.9%
      vs 12.5%). Consistent condom use with regular or non-regular partners was low
      (between 18.9% and 47.2%) regardless of the mixing pattern. However, parenteral
      risk for HIV transmission was relatively low in both groups. CONCLUSIONS: The
      transition of the HIV epidemic in China from injection drug use to sexual contact
      may be attributed to disassortative mixing in drug-use and sexual networks. HIV
      programs should consider disassortative mixing patterns when designing new
      behavioural interventions.

PMID- 26298585
TI  - Why participation matters for air quality studies: risk perceptions,
      understandings of air pollution and mobilization in a poor neighborhood in
      Nairobi, Kenya.
AB  - OBJECTIVES: With high urbanization rates, Sub-Saharan Africa is facing growing
      problems of poor air quality in its cities. We make a case for participatory
      approaches in air quality studies especially including those living in poor
      neighborhoods who may be particularly at risk from this trend. STUDY DESIGN: We
      used collaboration with a community based organization, interviews, focus group
      discussions and a community forum. METHODS: We conducted a pilot study to assess
      health risk perceptions of air pollution for civic-minded residents in Mathare,
      an informal settlement in Nairobi, Kenya. Simultaneously, we involved Mathare
      residents in measuring levels of PM2.5 and later presented these data at a
      community forum with the participants of the monitoring study and the focus group
      discussions. RESULTS: We found that participation in conducting and interpreting
      air quality studies helped residents improve their understanding of air pollution
      and also helped them develop responses to it. Initially, participants associated
      air pollution with a bad odor or discomfort rather than their health, but once
      the connection to health was made through participation, they sought more
      information about air quality data and its hazards. Some residents also came up
      with strategies for coping with their environment and its risks. CONCLUSIONS:
      These results point to the potential of including participation in air quality
      monitoring as a way to increase awareness and support local action to address it.
      Discussion and sharing of results at the local level as well as at a wider policy
      level will be critical for advocacy to improve air quality.

PMID- 26298586
TI  - A model for the coupling of the Greater Bairam and local environmental factors in
      promoting Rift-Valley Fever epizootics in Egypt.
AB  - OBJECTIVES: Rift-Valley Fever (RVF) is a zoonotic mosquito-borne disease in
      Africa and the Arabian Peninsula. Drivers for this disease vary by region and are
      not well understood for North African countries such as Egypt. A deeper
      understanding of RVF risk factors would inform disease management policies. STUDY
      DESIGN: The present study employs mathematical and computational modeling
      techniques to ascertain the extent to which the severity of RVF epizootics in
      Egypt differs depending on the interaction between imported ruminant and
      environmentally-constrained mosquito populations. METHODS: An ordinary
      differential system of equations, a numerical model, and an individual-based
      model (IBM) were constructed to represent RVF disease dynamics between localized
      mosquitoes and ruminants being imported into Egypt for the Greater Bairam. Four
      cases, corresponding to the Greater Bairam's occurrence during distinct quarters
      of the solar year, were set up in both models to assess whether the different
      season-associated mosquito populations present during the Greater Bairam resulted
      in RVF epizootics of variable magnitudes. RESULTS: The numerical model and the
      IBM produced nearly identical results: ruminant and mosquito population plots for
      both models were similar in shape and magnitude for all four cases. In both
      models, all four cases differed in the severity of their corresponding simulated
      RVF epizootics. The four cases, ranked by the severity of the simulated RVF
      epizootics in descending order, correspond with the occurrence of the Greater
      Bairam on the following months: July, October, April, and January. The numerical
      model was assessed for sensitivity with respect to parameter values and exhibited
      a high degree of robustness. CONCLUSIONS: Limiting the importation of infected
      ruminants beginning one month prior to the Greater Bairam festival (on years in
      which the festival falls between the months of July and October: 2014-2022) might
      be a feasible way of mitigating future RVF epizootics in Egypt.

PMID- 26298587
TI  - Close proximity to busy roads increases the prevalence and onset of cardiac
      disease--Results from RHINE Tartu.
AB  - OBJECTIVES: To analyze whether living close to a busy road would increase the
      risk of having cardiac disease and hypertension. STUDY DESIGN: Longitudinal cross
      sectional study. METHODS: We used cross-sectional longitudinal questionnaire data
      from the RHINE study for Tartu in 2000/2001 and 2011/2012. Home addresses of the
      respondents were geocoded and traffic data obtained from annually conducted
      traffic counts in Tartu. Relationships between proximity to a busy road and self
      reported cardiac disease and hypertension were analyzed with multiple logistic
      regression. RESULTS: In terms of total traffic (>=10,000 vehicles per day) within
      a 150-m zone of a busy road, the odds ratio (OR) for prevalence of cardiac
      disease was significant in 2000/2001 (1.91, 95% CI 1.15-3.16) and 2011/2012
      (1.58, 95% CI 1.01-2.47). Prevalence of hypertension was significant only in
      2011/2012 (1.61, 95% CI 1.08-2.39). In terms of heavy duty vehicle traffic (>=500
      vehicles per day) within a 150-m zone in 2000/2001, the OR was 1.52 (95% CI 1.04
      2.24) and 1.49 (95% CI 1.02-2.17) respectively for the prevalence of cardiac
      disease and hypertension. In 2011/2012 no significant relationship between heavy
      duty vehicle traffic and cardiac disease or hypertension was found. We also saw a
      significant relationship between total traffic and the onset of cardiac disease
      (OR = 2.04, 95% CI 1.07-3.87). CONCLUSIONS: This study showed that living closer
      than 150 m to a busy road can increase the odds of having cardiac disease and
      hypertension, which should be taken into account in city planning.

PMID- 26298588
TI  - A systematic review of studies on the prevalence of insomnia in university
      students.
AB  - OBJECTIVES: Many studies have shown that insomnia is a common problem among
      university students, but there are wide variations in the prevalence of insomnia.
      In this systematic review, we aimed to explore the prevalence of insomnia among
      university students using scientific and conclusive methods. STUDY DESIGN: A
      systematic review is designed to analyze the studies reporting on prevalence of
      insomnia among university students. METHODS: Systemic searches were conducted in
      PubMed, BioMed Central, EBSCO, ScienceDirect, Ovid LWW and Medline databases
      between January 2000 and July 2014, The Meta analyst software was used to
      calculate the prevalence rate of each study, the pooled means of prevalence rates
      and 95% CIs across studies were then calculated and presented. RESULTS: Seven
      articles that met the inclusion and exclusion criteria were selected. The overall
      sample size in the current review was 16,478, with a minimum of 219 and a maximum
      of 10,322. The prevalence rates of the seven studies ranged between 9.4% (95%CI
      8.8-10.0%) and 38.2% (95% CI 35.4-41.1%). Overall, the total students studied
      with a weighted mean prevalence of 18.5% (95% CI 11.2-28.8%), considerably higher
      than rates of 7.4% (95% CI 5.8-9.0%) reported in general population. CONCLUSIONS:
      This review emphasized that insomnia prevalence in university students is
      considerably higher than that in general population, suggested that more
      attention should be paid to insomnia in university students.

PMID- 26298589
TI  - The return of public health to local government in England: changing the
      parameters of the public health prioritization debate?
AB  - OBJECTIVES: To explore the influence of values and context in public health
      priority-setting in local government in England. STUDY DESIGN: Qualitative
      interview study. METHODS: Decision-makers' views were identified through semi
      structured interviews and prioritization tools relevant for public health were
      reviewed. Interviews (29) were carried out with Health and Wellbeing Board
      members and other key stakeholders across three local authorities in England,
      following an introductory workshop. RESULTS: There were four main influences on
      priorities for public health investment in our case study sites: an
      organizational context where health was less likely to be associated with health
      care and where accountability was to a local electorate; a commissioning and
      priority-setting context (plan, do, study, act) located within broader local
      authority priority-setting processes; different views of what counts as evidence
      and, in particular, the role of local knowledge; and debates over what
      constitutes a public health intervention, triggered by the transfer of a public
      health budget from the NHS to local authorities in England. CONCLUSIONS: The
      relocation of public health into local authorities exposes questions over
      prioritizing public health investment, including the balance across lifestyle
      interventions and broader action on social determinants of health and the extent
      to which the public health evidence base influences local democratic decision
      making. Action on wider social determinants reinforces not only the art and
      science but also the values and politics of public health.

PMID- 26298590
TI  - Should non-citizens have access to publicly funded health care?: a study of
      public attitudes and their affecting factors.
AB  - OBJECTIVES: To analyse public attitudes towards access for non-citizens to
      publicly funded health care and to assess the factors that affect such attitudes.
      STUDY DESIGN: Cross-sectional study. METHODS: Data from 29 countries were used
      for a multilevel regression, and data from four countries (United States, Sweden,
      Philippines, and Korea) were used for a linear regression. The data were
      collected from the International Social Survey Program (ISSP), the World Bank,
      the Organization for Economic Cooperation and Development (OECD), and the United
      Nations. The dependent variable was considered to be agreement for non-citizen
      access to publicly funded health care. The independent variables included: the
      gross national income (GNI), the gross national income coefficient (GINI), sex,
      age, education, household income, employment, health insurance, self-related
      health status, chronic illness, percent having insurance, percent having public
      insurance, percent employed, percent migrants, percent of health expenditure of
      the total gross domestic product (GDP), and percent of social expenditure of the
      total GDP. Egalitarianism for education policy (EEP), egalitarianism for health
      policy (EHP), and willingness to contribute to an egalitarian health policy
      (WCHP) were also examined. RESULTS: In the countries surveyed, more than half of
      the citizens agreed that non-citizens should have access to publicly funded
      health care. Agreement with that statement had a negative trend with respect to
      the GNI. The percent having public insurance and WCHP had a significantly
      positive association with agreement while the percent of those with insurance had
      a negative relationship. In the USA, household income, EHP, and WCHP were
      positively associated with agreement, while females were inversely associated
      with agreement. In Sweden, having health insurance had an inverse association to
      agreement while females, postsecondary education, health insurance coverage, and
      WCHP were positively associated with agreement. In the Philippines, household
      income, EEP, and EHP had significant negative associations with agreement while
      WCHP had a positive relationship. In Korea, household income and self-rated
      health status were positively associated with agreement, while postsecondary
      education had a negative association. CONCLUSION: Public attitudes towards
      allowing non-citizens to have access to publicly funded health care present high
      levels of variation, even among developed countries or countries with similar
      GDPs. The specific socio-economic conditions within a country and an individual's
      own social, demographic, and economic background can have different effects on
      the individual's attitudes towards non-citizens. On a global level, coverage of
      public health insurance plays an important role for enhancing the public's
      positive attitudes towards non-citizens' access to publicly funded health care.
      On a national level, health care policies tailored toward non-citizens based on
      the specific situation of each country and region are necessary.

PMID- 26298591
TI  - Utilization of Fenton-like reaction for antibiotics and resistant bacteria
      elimination in different parts of WWTP.
AB  - Utilization of relatively low-cost modification of Fenton reaction for the
      elimination of selected antibiotics and resistant coliforms in different part of
      wastewater treatment plant (WWTP) was studied. The concentration of antibiotics
      and occurrence of resistant gems in different stages of WWTP in the capital city
      of Slovakia - Bratislava was analyzed by LC-MS/MS technique. Consequently, Fenton
      like reaction was applied for the elimination of chemical and biological
      contaminants. Comparative study with classical Fenton reaction was also done.
      Very high concentrations of clarithromycin, ciprofloxacin and azithromycin in
      influent water were found. Coliform bacteria were predominantly resistant to
      ampicillin, ciprofloxacin and gentamicin. After the mechanical stage, the
      concentration of antibiotics in water was significantly decreased because of the
      sorption during this step. Biological step degraded 12 types of antibiotics.
      Analyses of effluent water showed very bad elimination of azithromycin (919ng/L)
      and clarithromycin (684ng/L). Contrary, ciprofloxacin was removed with very high
      efficiency (95%). The number of resistant bacteria was also significantly
      decreased in effluent water. In the case of Escherichia coli only ampicillin and
      gentamicin resistance bacteria were detected. Our results show that antibiotics
      as well as resistant bacteria were eliminated by the modification of classical
      Fenton reaction with high efficiency. The modification of the Fenton reaction can
      decrease the process wages, environmental impact. Moreover, the degradation
      process was easily controlled, monitored and tuned. 

PMID- 26298593
TI  - Bilateral spinal canal decompression via hemilaminectomy in cervical spondylotic
      myelopathy.
AB  - BACKGROUND: In cervical spondylotic myelopathy (CSM), laminoplasty (LP) or
      laminectomy plus fusion (LF) are accepted operative options and alternatives to
      anterior approaches. Both LP and LF have distinctive disadvantages, which might
      be avoided by unilateral hemilaminectomy and bilateral decompression of the
      spinal cord. METHODS: Description of the surgical technique, indications, and
      limitations. The potential advantages in comparison to LP and LF are discussed.
      CONCLUSIONS: Unilateral hemilaminectomy allows bilateral decompression of the
      whole dorsal circumference of spinal cord from nerve root to nerve root. The
      potential major advantages are a reduction of invasiveness by only unilateral
      muscle detachment, avoidance of implants, and shorter operation times.

PMID- 26298592
TI  - Intraparenchymal ventricular diverticula in chronic obstructive hydrocephalus:
      prevalence, imaging features and evolution.
AB  - BACKGROUND: Intraparenchymal cavities communicating with the ventricles may
      appear in patients with chronic obstructive hydrocephalus despite no identifiable
      surgerical, vascular or traumatic causes. The rate, features, pathogenesis,
      evolution and clinical impact of intraparenchymal diverticula have not been
      outlined, yet. METHODS: Brain MRIs of 130 patients (mean age: 11.3 years; age
      range: 0-67; 60 females) with chronic obstructive hydrocephalus were analyzed.
      The pathogenesis, neurosurgical treatment, ventricle size, signs of
      transependymal reabsorption and septum pellucidum integrity of the hydrocephalus
      were recorded. Subarachnoid outpouching of the ventricles, post-hemorrhagic
      parenchymal cavities, paths of ventricular shunting and cavities not
      communicating with the ventricles were excluded. Of patients with
      intraparenchymal diverticula, all previous available CT and MRI scans were
      evaluated. RESULTS: Eight patients (6.2 %, mean age: 18.7 years; age range: 2-42)
      harbored 11 intraparenchymal diverticula sprouting from the temporal (6),
      occipital (3) or frontal (2) horns of the lateral ventricles. Intraparenchymal
      diverticula were more frequent in males (p = 0.04) and older patients (18.7 +/-
      12.7 vs 11.3 +/- 9.8 years, p = 0.04). Their presence or evolution (mean
      neuroradiological follow-up 3.6 years; range: 0-8) showed a trend of association
      with hydrocephalus severity (bifrontal index) and did not correlate with the
      surgical treatment. In three patients the diverticula progressed during follow
      up. One patient presented with hemiparesis consistent with the intraparenchymal
      lesion and improved after ventricular shunting. A DTI study revealed that the
      cortico-spinal tract was partly included in the septum between the ventricle and
      the intraparenchymal diverticulum. CONCLUSIONS: Clinicians dealing with chronic
      severe obstructive hydrocephalus should be aware of ventricular intraparenchymal
      diverticulation. Studies aiming at clarifying their pathogenesis and proper
      management are warranted.

PMID- 26298594
TI  - Outcome and toxicity profile of salvage low-dose-rate iodine-125 stereotactic
      brachytherapy in recurrent high-grade gliomas.
AB  - BACKGROUND: The aim of this study was to provide an outcome and toxicity profile
      of salvage low-dose-rate iodine-125 (I-125) stereotactic brachytherapy (SBT) in
      patients with small, circumscribed malignant glioma recurrences. METHODS:
      Patients with malignant glioma recurrences consecutively undergoing salvage SBT
      from 2003 to 2011 were identified from our prospective tumor database. SBT was
      considered a potentially suitable treatment strategy for adult mostly
      multimodally pretreated patients (Karnofsky score of >= 70) with biopsy-proven,
      circumscribed, small (diameter <= 3.5 cm) recurrences. Exclusively temporary I
      125 seeds were used (reference dose: 50 Gy, dose rate: < 15 cGy/h). Study
      endpoints were time-to-treatment failure (TTF) after SBT, postrecurrence survival
      (PRS), and toxicity. Survival was assessed with the Kaplan-Meier method. Adverse
      events were categorized according to the RTOG/EORTC classification. Prognostic
      factors were obtained from proportional hazards models. RESULTS: Sixty-eight
      patients (28 WHO grade III, 40 WHO grade IV gliomas) were included. Fifty-nine
      patients had previously received external beam radiation. Median TTF and PRS were
      8.3 months and 13.4 months, respectively. TTF and PRS were longer for grade III
      gliomas than for glioblastomas (15.0 vs. 6.2 months and 28.1 vs. 9.3 months,
      respectively). Patients with grade III tumors were younger (p = 0.002). Favorable
      factors for TTF and PRS were age <= 50 years and a methylated O(6)-methylguanine
      DNA methyltransferase (MGMT)-promoter. Alternative models including tumor grade
      instead of age reached a similar good fit. Three patients suffered from grade I,
      one from grade II, and two from grade IV toxicity. CONCLUSIONS: Salvage SBT is
      feasible and safe even after previously performed external beam radiation.
      Favorable outcome measurements in particular for grade III recurrences deserve
      further prospective evaluation.

PMID- 26298595
TI  - Subarachnoid hemorrhage due to anterior inferior cerebellar artery aneurysms
      associated with Gamma Knife surgery for vestibular schwannomas.

PMID- 26298596
TI  - Poor man-rich man fluorescence. Is this really the problem?

PMID- 26298597
TI  - Response to the Letter to the Editor Surgery for high-grade unruptured
      arteriovenous malformations: era for a new paradox? by Bervini and Morgan.

PMID- 26298598
TI  - What Causes Late Perforation of the Jejuno-Jejunal Anastomosis After Roux-en-Y
      Gastric Bypass Surgery?

PMID- 26298599
TI  - Orbital-type trapping of elastic Lamb waves.
AB  - The interaction of laser-generated Lamb waves propagating in a plate with a sharp
      angle conical hole was studied experimentally and numerically. Part of the energy
      of the incident wave is trapped within the conic area in two ways: the
      antisymmetric Lamb wave orbiting the center of the hole and the wave localized at
      the acute edge. Parameters and conditions for optimal conversion of the incident
      wave into the trapped modes were studied in this work. Experiments were performed
      using the laser stroboscopic shearography technique, which delivers the time
      evolution of the acoustic field in the whole area of interest. The effect of
      trapping can be used for efficient damping, similar to the one-dimensional
      acoustical black hole effect. 

PMID- 26298600
TI  - De novo Diagnosis of Fabry Disease among Italian Adults with Acute Ischemic
      Stroke or Transient Ischemic Attack.
AB  - BACKGROUND AND PURPOSE: Cerebrovascular complications are often the first cause
      of hospitalization in patients with Fabry disease (FD). Screenings for FD among
      stroke patients have yielded discrepant results, likely as a result of
      heterogeneous or incomplete assessment. We designed a study to identify FD among
      adults 60 years of age or younger who were consecutively admitted for acute
      ischemic stroke or transient ischemic attack (TIA) to a stroke neurology service
      in Italy. METHODS: Patients with first-ever or recurrent events were included,
      irrespective of gender, risk factors, or stroke type. We screened male patients
      using alpha-galactosidase A enzyme assay, and female patients using DNA
      sequencing. FD was eventually established after a broad multidisciplinary
      discussion. RESULTS: We screened 108 patients (61% males, median age: 48 years);
      84% of these patients had stroke. De novo FD diagnosis was established in 3
      patients (2.8%; 95% confidence interval, .57-8.18): a 59-year-old man with
      recurrent lacunar-like strokes and multiple risk factors; a 42-year-old woman
      with recurrent cryptogenic minor strokes; and a 32-year-old woman with recurrent
      strokes previously attributed to Behcet's disease. Screened patients were
      systematically asked for typical FD symptoms; each of the de novo patients
      reported one or more of the following: episodes of hand/foot pain during fever,
      angiokeratoma, and family history of heart disease. In all of the patients events
      were recurrent, and lacunar-like infarcts characterized their brain imaging.
      CONCLUSIONS: Prevalence of FD among nonselected adults 60 years of age or younger
      with acute ischemic stroke or TIA is not negligible. A systematic search for FD
      in a stroke setting, using a comprehensive clinical, biochemical, and genetic
      screening protocol, may be worthwhile.

PMID- 26298601
TI  - Water hardness and eczema at 1 and 4 y of age in the INMA birth cohort.
AB  - BACKGROUND: Exposure to hard water has been suggested as a risk factor for eczema
      in childhood, based on limited evidence from two ecologic and two cross-sectional
      studies. OBJECTIVES: We evaluate this hypothesis for the first time in early
      infancy using prospective data from a mother-child cohort study. METHODS: We used
      data from the INMA cohorts in Gipuzkoa, Sabadell and Valencia, Spain (N=1638).
      Current and ever eczema, bathing frequency and duration and covariables were
      collected by questionnaires at 14 months (14 m) and 4 years (4 y). Calcium
      carbonate (CaCO3) level in municipal water was assigned to home addresses at
      birth, 14 m and 4 y. We calculated Odds Ratio (OR) of eczema related to CaCO3 at
      home, bath exposure and a combination of both. RESULTS: Prevalence of eczema ever
      was 18.4% at 14 m and 33.4% at 4 y. Mean CaCO3 ranged from 51.6 to 272.8 mg/L
      among areas. No association was detected between water hardness at home and
      current or ever eczema. Adjusted OR was 0.79 (95%CI=0.45, 1.39) at 14 m and 0.93
      (0.56, 1.52) at 4 y among children in the highest vs. lowest tertiles of CaCO3.
      Bath exposure alone or in combination with water hardness did not increase the OR
      of eczema at 14 m or 4 y either. CONCLUSIONS: We did not find an association
      between eczema and water hardness at home or bathing exposure during the first
      four years of life. This first cohort study in a critical age period with
      improved exposure assessment does not confirm the association suggested among
      children by previous studies.

PMID- 26298602
TI  - Antibiotic susceptibility of Legionella pneumophila strains isolated from
      hospital water systems in Southern Italy.
AB  - OBJECTIVES: The purpose of this study was to describe the susceptibility of
      environmental strains of Legionella spp. to 10 antimicrobials commonly used for
      legionellosis therapy. A study of environmental strains could be useful to timely
      predict the onset of antibiotic resistance in the environment before it is
      evidenced in clinical specimens. METHODS: The minimum inhibitory concentrations
      (MICs) of 100 environmental Legionella pneumophila (Lpn) strains belonging to
      serogroups (sgs) 1, 6, 8, and 10 were tested using the E-test methodology on
      buffered charcoal yeast extract agar supplemented with alpha-ketoglutarate. The
      most frequent sgs were selected from those obtained during microbiological
      surveillance conducted in 2014 in a hospital in Southern Italy. The MICs were
      read after 2 days of incubation at 35  degrees C in a humidified atmosphere
      without CO2. RESULTS: All isolates were inhibited by low concentrations of
      fluoroquinolones and macrolides. Rifampicin was the most active drug against the
      isolates in vitro. All Lpn isolates were inhibited by the following drugs (in
      decreasing order of their MICs): doxycycline>tigecycline>cefotaxime. The MICs of
      azithromycin, ciprofloxacin, levofloxacin, moxifloxacin, and tigecycline were
      significantly lower for Lpn non-sg 1 than Lpn sg 1 isolates. CONCLUSIONS:
      Susceptibility testing of Legionella strains to appropriate antibiotics should be
      performed often to evaluate the possible emergence of resistance, to improve the
      outcomes of patients, and to reduce the direct costs associated with
      hospitalization.

PMID- 26298603
TI  - Commentary: Plastic ocean and the cancer connection: 7 questions and answers.
AB  - A plethora of recent scientific reports testifies to challenges the world is
      facing from an ever-increasing marine plastic pollution. Toxicological concerns
      have been put forward, but possible links between the now ubiquitous synthetic
      polymers and human as well as wildlife cancers remain to be investigated. Hence,
      this commentary which addresses seven questions. Given numerous uncertainties on
      the factual impacts of plastics, we should embark on empirical studies into the
      validity of biologically plausible links between plastic residues and cancers and
      concomitantly consider ways to reduce plastics in the world within and around us.

PMID- 26298604
TI  - Sequential enrichment of singly- and multiply-phosphorylated peptides with
      zwitterionic hydrophilic interaction chromatography material.
AB  - An interesting and novel method for the selective and sequential enrichment of
      singly- and multiply-phosphorylated peptides with a zwitterionic material "Click
      TE-Cys" is presented. Retention mechanisms between phosphopeptides and Click TE
      Cys are systematically investigated by checking the influence of acetonitrile
      content, pH value, and buffer concentration on the retention of phosphopeptides.
      Both hydrophilic interaction and electrostatic interaction are involved in
      retention between phosphopeptides and Click TE-Cys. Based on these results, an
      optimized method is established for selective enrichment of phosphopeptides using
      Click TE-Cys. This method not only exhibits high selectivity for phosphopeptides,
      but also fractionates singly- and multiply-phosphorylated peptides into two
      fractions. This method was evaluated using relatively complex samples, including
      peptide mixtures of alpha-casein and bovine serum albumin (BSA) at a molar ratio
      of 1:10 and skim milk. This efficient and optimized protocol has great potential
      for enriching multiply-phosphorylated peptides and could be a valuable tool for
      specific enrichment of phosphopeptides in phosphoproteome analysis. 

PMID- 26298605
TI  - Gas chromatography-tandem mass spectrometry with atmospheric pressure chemical
      ionization for fluorotelomer alcohols and perfluorinated sulfonamides
      determination.
AB  - Ionization and in source-fragmentation behavior of four fluorotelomer alcohols
      (FTOH) (4:2 FTOH, 6:2 FTOH, 8:2 FTOH and 10:2 FTOH) and four N-alkyl fluorooctane
      sulfonamides/-ethanols (N-MeFOSA, N-EtFOSA, N-MeFOSE and N-EtFOSE) by APCI has
      been studied and compared with the traditionally used EI and CI. Protonated
      molecule was the base peak of the APCI spectrum in all cases giving the
      possibility of selecting it as a precursor ion for MS/MS experiments. Following,
      CID fragmentation showed common product ions for all FOSAs/FOSEs (C4F7 and C3F5).
      Nevertheless, the different functionality gave characteristic pattern
      fragmentations. For instance, FTOHs mainly loss H2O+HF, FOSAs showed the losses
      of SO2 and HF while FOSEs showed the losses of H2O and SO2. Linearity,
      repeatability and LODs have been studied obtaining instrumental LODs between 1
      and 5fg. Finally, application to river water and influent and effluent waste
      water samples has been carried out in order to investigate the improvements in
      detection capabilities of this new source in comparison with the traditionally
      used EI/CI sources. Matrix effects in APCI have been evaluated in terms of signal
      enhancement/suppression when comparing standards in solvent and matrix. No matrix
      effects were observed and concentrations found in samples were in the range of 1
      100pgL(-1) far below the LODs achieved with methods previously reported. Unknown
      related perfluoroalkyl substances, as methyl-sulfone and methyl-sulfoxide
      analogues for FTOHs, were also discovered and tentatively identified. 

PMID- 26298606
TI  - A series of strategies for solving the shortage of reference standards for multi
      components determination of traditional Chinese medicine, Mahoniae Caulis as a
      case.
AB  - In order to solve the bottleneck of reference standards shortage for
      comprehensive quality control of traditional Chinese medicines (TCMs), a series
      of strategies, including one single reference standard to determine multi
      compounds (SSDMC), quantitative analysis by standardized reference extract
      (QASRE), and quantitative nuclear magnetic resonance spectroscopy (qNMR) were
      proposed, and Mahoniae Caulis was selected as an example to develop and validate
      these methods for simultaneous determination of four alkaloids, columbamine,
      jatrorrhizine, palmatine, and berberine. Comprehensive comparisons among these
      methods and with the conventional external standard method (ESM) were carried
      out. The relative expanded uncertainty of measurement was firstly used to compare
      their credibility. The results showed that all these three new developed methods
      can accurately accomplish the quantification by using only one purified reference
      standard, but each of them has its own advantages and disadvantages as well as
      the specific application scope, which were also discussed in detail in this
      paper. 

PMID- 26298607
TI  - Autosomal recessive axonal polyneuropathy in a sibling pair due to a novel
      homozygous mutation in IGHMBP2.
AB  - Charcot-Marie-Tooth disease is a group of genetically heterogeneous disorders
      characterized by a sensorimotor polyneuropathy with subsequent muscle atrophy,
      areflexia, and sensory loss. More than 60 genes have been linked to Charcot-Marie
      Tooth phenotypes, including IGHMBP2. Until recently, mutations in IGHMBP2 were
      exclusively associated with spinal muscular atrophy with respiratory distress
      (SMARD1). We present a sibling pair with a novel homozygous truncating mutation
      in IGHMBP2. The patients presented with childhood-onset distal weakness, wasting
      in the upper and lower limbs, areflexia and decreased sensation, but no
      respiratory involvement. Exome sequencing was performed and a homozygous variant
      was identified (c.2601_2604del; p.Lys868Profs*109). Sanger sequencing confirmed
      the presence of this variant in a homozygous state in the two affected siblings,
      while both parents were heterozygous. Further analyses showed decreased mRNA and
      IGHMBP2 protein in a lymphoblast cell line derived from one of the siblings. We
      demonstrate the utility of next-generation sequencing in reaching a molecular
      diagnosis for a heterogeneous condition such as Charcot-Marie-Tooth. Taken
      together, our data and that from the literature suggest that the spectrum of
      clinical presentations associated with mutations in IGHMBP2 may be secondary, at
      least in part, to the amount of residual protein. 

PMID- 26298608
TI  - Spinal and bulbar muscular atrophy and Charcot-Marie-Tooth type 1A: Co-existence
      of two rare neuromuscular genetic diseases in the same patient.
AB  - Spinal and bulbar muscular atrophy is an X-linked neuromuscular disease caused by
      a trinucleotide CAG repeat expansion in the androgen receptor gene; it is
      clinically characterized by adult-onset, slowly progressive weakness and atrophy
      mainly affecting proximal limb and bulbar muscles. Charcot-Marie-Tooth disease
      type 1A is an autosomal dominant polyneuropathy due to peripheral myelin protein
      22 gene duplication and characterized by slowly progressive distal limb muscle
      weakness, atrophy and sensory loss with foot deformities. Here we report the co
      occurrence of both neuromuscular genetic diseases in the same male patient.
      Difficulties in climbing stairs and jaw weakness were presenting symptoms
      consistent with SBMA. However, predominant distal weakness and bilateral pes
      cavus were rather suggestive of a hereditary polyneuropathy. The combination of
      two diseases, even if extremely rare, should be considered in the presence of
      atypical symptoms; in the case of genetic diseases this event may have important
      implications on family members' counseling. 

PMID- 26298609
TI  - Treatable renal failure found in non-ambulatory Duchenne muscular dystrophy
      patients.
AB  - Duchenne muscular dystrophy (DMD) is a progressive muscular disorder in which
      respiratory and heart failures are the main causes of death. Intensive
      intervention in respiratory and cardiac function has dramatically improved the
      prognosis; however, dysfunction in other multiple organs may emerge in the later
      stages of the disease. We report the case of four non-ambulatory DMD patients who
      presented with renal failure. Common findings included decreased fluid intake,
      use of diuretics, and presence of chronic heart failure. The levels of serum
      cystatin C (CysC), a marker of kidney function unaffected by reduced muscle mass,
      were elevated in all four patients. In two patients, renal failure improved by
      increasing fluid intake, and discontinuing or reducing the dose of diuretics. The
      findings suggest that non-ambulatory DMD patients are at a risk of reduced kidney
      perfusion, which potentially leads to prerenal failure. Therefore, in DMD
      patients, dehydration signs and CysC levels should be monitored. 

PMID- 26298610
TI  - Manipulators live better, but are they always parasites?
AB  - A recent study reports partner manipulation for an interaction that was
      considered a reward-for-defence mutualism. Secretions of lycaenid caterpillars
      altered ant locomotion and aggressiveness, likely by manipulating dopaminergic
      signalling. This study opens the question whether such manipulation is common and
      whether manipulation necessarily characterises an interaction as parasitism. 

PMID- 26298611
TI  - From the Editor's perspective....

PMID- 26298612
TI  - Venous thromboembolism: An overview.
AB  - Venous thromboembolism (VTE) is a disease that includes both deep vein thrombosis
      (DVT) and pulmonary embolism (PE). It is a common, lethal disorder that affects
      both hospitalized and nonhospitalized patients. PE and DVT are 2 clinical
      presentations of VTE and share the same predisposing factors. In most cases, PE
      is a consequence of DVT. This article discusses the predisposing factors,
      prevalence, and individuals who are at risk of developing this often life
      threatening disease. 

PMID- 26298613
TI  - Risk level analysis for deep vein thrombosis (DVT): A study of Turkish patients
      undergoing major orthopedic surgery.
AB  - Deep vein thrombosis (DVT) is a prevalent problem for orthopedic patients,
      particularly owing to the nature of operative interventions and treatment
      procedures, predisposing to an high risk of DVT. This descriptive study was
      conducted to determine the levels of risk, the risk factors, and their odds ratio
      for DVT in patients undergoing major orthopedic surgery. Data were collected
      using a Patient Information Form and the Autar DVT Risk Assessment Scale (DVTRAS)
      in orthopedic wards of a university hospital on postoperative day 2. Data were
      analyzed using descriptive, comparative analysis, and binary logistic regression.
      The 102 patients (mean age, 52.58 +/- 21.58 years) were hospitalized for a mean
      of 14.35 +/- 14.56. Of the sample, 53.9% were female, 65.7% had a history of
      previous surgery, and 54.9% had undergone total hip/knee arthroplastic surgery,
      67.6% of patients wore graduated compression stockings, and 62.7% were
      administered liquid infusion. Those patients had moderate risk score (12.77 +/-
      5.66) in the Autar DVTRAS. According to binary logistic regression analysis,
      aging, obesity, immobility, and acute and chronic diseases were significant risk
      factors for postoperative DVT (p <= .05). This study highlights evidence on the
      degree of DVT risk, risk factors, and impact of venous thromboembolism in
      patients undergoing major orthopedic operations. For evidence-based clinical
      practice, these high-level risk factors should be taken into account in the
      prevention of DVT in orthopedic patients. 

PMID- 26298614
TI  - Functional status of nursing home residents before and after abdominal aortic
      aneurysm repair.
AB  - Although many trials have evaluated abdominal aortic aneurysm (AAA) repair, the
      impact of these procedures on the functional status of frail elderly patients is
      not well-described. The effects of elective open AAA repair (OAR) and
      endovascular AAA repair (EVAR) and comorbidities were evaluated for their impact
      on functional trajectories after discharge. Medicare inpatient claims were linked
      with nursing home assessment data to identify elective admissions for OAR and
      EVAR. A functional score (range, 0-28; higher scores indicate greater impairment)
      was calculated before and after interventions. Logistic regression was used to
      develop a propensity score for receiving EVAR because residents were not
      randomized. Hierarchical linear modeling determined the effect of surgery on
      residents' function, controlling for prehospital function, hospital length of
      stay (LOS), stroke, and the propensity score.Fifty-two residents underwent OAR
      and 161 underwent EVAR. Most (65.3%) were men and 62.0% were from 76 to 85 years
      old. Mean LOS was 8.3 days for OAR and 5.1 days for EVAR. Of the residents, 47.4%
      had good prehospital function (activities of daily living [ADL] score of 0-10),
      and 48.4% were moderately impaired (ADL score of 11-20). Higher baseline ADL
      score, increased LOS, and stroke were associated with worse trajectories.
      Procedure type was not significantly related to postoperative function or the
      subsequent rate of improvement. OAR and EVAR were associated with similar initial
      declines and comparable postoperative trajectories, suggesting that less invasive
      EVAR was not associated with improved functional preservation compared with OAR.
      LOS was found to be higher than expected in the frail elderly after EVAR; longer
      stays were associated with poorer functional trajectories. Higher baseline ADL
      scores were significantly associated with inferior functional status after both
      procedures. Evaluation of preoperative function may assist physicians in
      predicting outcomes in this high-risk population. 

PMID- 26298615
TI  - Disease understanding in patients with intermittent claudication: A qualitative
      study.
AB  - The aim of our qualitative study was to investigate the understanding of patients
      with intermittent claudication (IC) regarding the etiology and atherosclerotic
      nature of their disease. Patients were recruited from participants of the SUPER
      study, a randomized trial comparing angioplasty and supervised exercise therapy
      for alleviation of IC owing to an iliac artery obstruction. Patients were
      submitted to explorative, semistructured, in-depth interviews that were fully
      transcribed, coded, and categorized. We interviewed 19 patients. The majority of
      respondents (79%) recognized smoking as a major risk factor contributing to the
      etiology of IC. However, nearly one-half (47%) underestimated the effects of
      unhealthy dietary and exercise patterns. In contrast, a substantial number of
      respondents (42%) overestimated the contribution of genetics to the etiology of
      their disease. Most respondents (79%) were unaware of the fact that IC implies
      systemic atherosclerosis.This study shows that the patients' interpretation of
      the etiology and nature of IC was mostly incorrect. Therefore, we suggest that
      health care providers enhance counseling about etiologic factors and the systemic
      nature of IC to optimize outcomes of lifestyle adjustments. 

PMID- 26298616
TI  - Trimodal venous thromboembolism prophylaxis in total knee replacement: A quality
      improvement project for best care practices.
AB  - Venous thromboembolism (VTE) is a highly significant clinical and public health
      concern in the United States, particularly in the surgical population, where
      approximately 2 million patients of >30 million operative procedures performed
      annually in the United States experience postoperative complications. Previous
      well-documented research has revealed that longstanding national guidelines that
      call for risk stratification and trimodal VTE prophylaxis, a comprehensive
      modality incorporating 3 arms of prophylaxis-chemical, mechanical, and early
      ambulation-suffer from significant levels of nonadherence. The fallout includes a
      disconcerting magnitude of cases of preventable morbidity and mortality, and
      exertion of a weighty cost burden on the US health care system. This evidence
      based quality improvement project investigated the level of adherence, and the
      causes of nonadherence, to national guidelines for VTE prophylaxis among total
      knee replacement patients at a prominent tertiary facility in central
      Massachusetts. Chief among the findings, analysis of documented data, augmented
      by data collected from unannounced mechanical prophylaxis adherence audits,
      identified frontline staff negligence as the principal cause of nonadherence in
      the mechanical arm. Overall, the project helped to underscore optimal VTE
      prophylaxis as a synergistic amalgamation of the trimodal methodology's
      complementary individual component efficacies. 

PMID- 26298617
TI  - The missing vital sign: The significance of bilateral arm blood pressures.

PMID- 26298618
TI  - Review of article: Early cardiopulmonary resuscitation in out-of-hospital cardiac
      arrest. Hasselqvist-Ax I, Riva G, Herlitz J, Rosenqvist M, et al (N Engl J Med
      2015;374:2307-2315).

PMID- 26298619
TI  - The impact of a three-factor prothrombin complex concentrate on the
      anticoagulatory effects of the factor Xa inhibitor edoxaban.
AB  - BACKGROUND: Edoxaban, a direct factor Xa inhibitor, is a once-daily, non-vitamin
      K antagonist oral anticoagulant. There is no established method to reverse the
      activity of non-vitamin K oral anticoagulants in cases of hemorrhage or urgent
      surgery. This study evaluated the ability of a 3-factor prothrombin complex
      concentrate (3F-PCC) to reverse the anticoagulatory effects of edoxaban. METHODS:
      In this phase 1 study, 24 healthy subjects were randomly assigned to receive a
      single dose of 60 or 180mg edoxaban, followed by placebo, 25IU/kg 3F-PCC, or
      50IU/kg 3F-PCC. Edoxaban pharmacokinetics and pharmacodynamics, including the
      primary endpoint of prothrombin time (PT) and endogenous thrombin potential
      (ETP), were assessed. D-dimer and prothrombin fragment 1 and 2 (F1+2) were also
      measured. RESULTS: Overall, there were no apparent consistent effects of 3F-PCC
      on edoxaban pharmacokinetics. Administration of 3F-PCC 25 or 50IU/kg with
      edoxaban 60 or 180mg did not substantially accelerate the return of PT to
      baseline levels. However, infusion of 3F-PCC 25 and 50IU/kg did substantially
      accelerate return to baseline of ETP compared with placebo. D-dimer and F1+2 data
      did not indicate any lasting procoagulant effects of 3F-PCC infusion, although a
      transient increase in F1+2 was noted during and after 3F-PCC infusion. Edoxaban
      and 3F-PCC co-administration was well tolerated in normal healthy subjects.
      CONCLUSIONS: There was no apparent reversal of PT prolongation with 3F-PCC
      following edoxaban infusion, but ETP was completely reversed. Co-administration
      of 3F-PCC was well tolerated, but a dose-dependent increase in F1+2 may reflect a
      procoagulant risk.

PMID- 26298620
TI  - Corticosteroids and immune checkpoint blockade.

PMID- 26298621
TI  - EBV epiglottitis: Primary supraglottic viral infection in a pediatric
      immunocompetent host.
AB  - In this report we describe a case in which a previously healthy 7 year-old male
      developed acute epiglottitis secondary to Epstein-Barr virus (EBV) infection.
      This patient required fiberoptic intubation and ICU stay. We discuss epiglottitis
      diagnosis and management with EBV as the primary etiologic agent. 

PMID- 26298622
TI  - Furlow palatoplasty for previously repaired cleft palate with velopharyngeal
      insufficiency.
AB  - OBJECTIVE: Velopharyngeal insufficiency (VPI) is a common complication after
      cleft palate repair, it may be due to lack of levator sling reconstruction and/or
      palatal shortening. Furlow palatoplasty has the advantages of retro-positioning
      of levator palati muscles and palatal lengthening. The aim of this study was to
      assess the efficacy of Furlow palatoplasty in the treatment of VPI in patients
      who undergone previous palatoplasty. METHODS: Twenty-three children with post
      palatoplasty VPI were included in the study. Furlow technique which was not used
      in the primary repair, has been used as a secondary corrective surgery.
      Preoperative and postoperative evaluation of velopharyngeal function was
      performed, using auditory perceptual assessment (APA) and nasometry for speech,
      and flexible nasopharyngoscopy for velopharyngeal closure. RESULTS: Significant
      improvement of APA and nasalance score for oral and nasal sentences was achieved.
      Flexible nasopharyngoscopy showed complete velopharyngeal closure in 19 patients
      (82%) postoperatively. CONCLUSION: Furlow palatoplasty is considered a useful
      treatment option for VPI in patients with previously repaired cleft palate, it
      improves the speech and velopharyngeal closure.

PMID- 26298623
TI  - Scedosporium apiospermum causing otomycosis in an immunocompetent child with
      tympanostomy tubes: Management of this rare entity.
AB  - Infection following a tympanostomy tube insertion is a common occurrence.
      Scedosporium apiospermum is a filamentous fungus mainly isolated in water and
      soil. There have been no reported cases of S. apiospermum infection of an
      immunocompetent individual with a tympanostomy tube in situ. A child was referred
      with unilateral otorrhoea failing to respond to conventional treatment in the
      community. S. apiospermum was identified following specialist testing. An
      extended course of anti-fungal treatment led to complete resolution. Due to the
      rare occurrence of aural S. apiospermum and unreported nature, it should be
      managed in a multidisciplinary setting. 

PMID- 26298624
TI  - Incidence of velopharyngeal insufficiency and oronasal fistulae after cleft
      palate repair: A retrospective study of children referred to Isfahan Cleft Care
      Team between 2005 and 2009.
AB  - OBJECTIVE: The purpose of this study is to determine the incidence of
      velopharyngeal insufficiency (VPI) and fistulae development in patients seen by
      the Isfahan Cleft Care Team and also determine the association of gender, age at
      repair, and cleft type with the incidence of each. METHODS: This retrospective
      study was completed using records of patients referred to Isfahan Cleft Care Team
      between 2005 and 2009. One hundred thirty-one patients with a history of cleft
      palate (with or without cleft lip) who had undergone primary palate repair and
      were at least 4 years of age at the time of the speech evaluation were included
      in this review. The main outcome of this study was the incidence of fistulae and
      hypernasality following palatoplasty. A secondary outcome was the association of
      gender, age at the time of repair, and cleft type on the incidence of fistulae
      and hypernasality. RESULTS: A post-surgical fistula was present in 23.7% of the
      patients studied. Fistula rates were significantly higher in patients who had
      undergone repair of bilateral clefts of the lip and palate (40.9%) than for those
      patients who had undergone repair of a unilateral cleft lip and palate (16.9%)
      (p=0.02). Presence of a fistula was not associated with gender (p=0.99) or age at
      time of primary surgical repair (p=0.71). Mild hypernasality was noted in 15.3%
      of patients. Moderate or severe hypernasality was present in 66.5% of the
      patients and the remaining cases presented with normal resonance. Severe
      hypernasality was significantly higher in patients with a Veau IV type cleft as
      compared to patients with Veau III cleft types (p=0.04). There was a
      significantly higher incidence of hypernasality in boys than in girls (p<0.001).
      The association of age at the time of palatal repair and incidence of
      hypernasality was not significant (r=0.13, p=0.07). CONCLUSIONS: Overall, post
      surgical complications were high in this cohort of patients who had undergone
      cleft palate repair by Isfahan Cleft Care Team during the study time frame.
      Therefore, there is a high priority need for increased training of best practices
      for the surgeons.

PMID- 26298625
TI  - Comparing the Use of Centers for Disease Control and Prevention and World Health
      Organization Growth Charts in Children with Cystic Fibrosis through 2 Years of
      Age.
AB  - OBJECTIVE: To examine differences between use of World Health Organization (WHO)
      and Centers for Disease Control and Prevention (CDC) growth reference in children
      with cystic fibrosis (CF) up to 2 years of age. STUDY DESIGN: Growth from 1-24
      months in 2587 children, born 2003-2006 and recorded in the US CF Foundation
      Registry, was evaluated using WHO and CDC references. RESULTS: In both boys and
      girls with CF aged 1-24 months, use of WHO charts resulted in ~8 percentile lower
      length-for-age and ~13% higher short stature rate (length-for-age <5th
      percentile). WHO weight-for-age was ~9 percentile lower prior to age 6 months,
      crossed at 6-7 months, and remained ~14 percentile higher at 8-24 months. WHO
      weight-for-length (WFL) percentile (WFLp) was similar before 12 months but ~10
      percentile higher at 12-24 months compared with CDC. When using WHO charts, 9% of
      children had underweight (WFLp <50th) classified differently and this rate varied
      with age: 4% in the first year, 7% at 12, 13% at 15, and 16% at 18 months,
      respectively. Weight status assessed by WHO body mass index (BMI) charts was
      different from WHO WFL charts. At 24 months when switching back to CDC, 26% of
      children with normal WFLp on WHO charts appeared underweight on CDC charts. A
      70th percentile of WHO BMI percentile was equivalent to the 50th percentile CDC
      BMI percentile. CONCLUSIONS: Growth status in children with CF differed when
      using WHO and CDC references, particularly during the second year of life. These
      differences need to be considered for all uses of growth assessment in CF.

PMID- 26298626
TI  - Kasabach-Merritt Phenomenon.

PMID- 26298627
TI  - Assessment of Transition Readiness in Adolescents and Young Adults with Heart
      Disease.
AB  - OBJECTIVES: To evaluate transition readiness, including perceived knowledge
      deficits, self-efficacy, and self-management behaviors, in 13- to 25-year-olds
      with congenital heart disease or heart transplant and to examine the
      relationships between transition readiness assessment, information seeking
      behavior, and quality of life (QOL). STUDY DESIGN: In this cross-sectional study,
      patients (n = 164) completed the Transition Readiness Assessment and the
      Pediatric Quality of Life Inventory using an e-tablet, web-based format at a
      routine clinic visit. RESULTS: Median patient age was 18.1 years (range 13.0
      25.5). Average perceived knowledge deficit score (% of items with no knowledge)
      was 25.7% (range 0%-75%). On a 100-point scale, the mean score was 72.0 +/- 17.2
      for self-efficacy and 49.7 +/- 17.5 for self-management. Knowledge deficits were
      negatively correlated with self-efficacy (r = -0.45, P < .0001) and self
      management (r = -0.36, P < .0001). Overall, 66% of patients requested information
      (73% >= 18 years old). Higher psychosocial QOL scores were correlated with lower
      knowledge deficit scores (r = -0.21, P = .01) and higher perceived self-efficacy
      scores (r = 0.41, P < .0001). CONCLUSIONS: Transition knowledge deficits are
      common and associated with decreased self-efficacy and self-management skills in
      adolescents and young adults with heart disease. Greater transition knowledge and
      perceived self-efficacy are associated with better psychosocial QOL. Routine
      assessment of transition readiness is recommended to facilitate recognition of
      deficits and interventions to promote successful transition outcomes.

PMID- 26298629
TI  - VEGFR2 predicts decreased patients survival in soft tissue sarcomas.
AB  - AIMS: Tyrosine kinases are promising targets for personalized medicine, and new
      drugs are currently in phase 2 and phase 3 clinical trials. However, expression
      analysis of tyrosine kinases as predictive biomarkers is still not a standard
      approach. Furthermore, only limited studies have investigated the expression of
      tyrosine kinase receptors on the protein level. In this study, we analysed a well
      characterised group of soft tissue sarcomas for different tyrosine kinase
      receptors and correlated the results with clinicopathological parameters,
      including survival. METHODS: 275 soft tissue sarcomas of our Sarcoma center at
      the Ludwig-Maximilians-University (LMU) were reinvestigated and categorized
      according to the current WHO classification system. The tumor collective included
      undifferentiated pleomorphic sarcomas (n=81), leiomyosarcomas (n=50), synovial
      sarcomas (n=27), liposarcomas (n=51), angiosarcomas (n=43) and other soft tissue
      sarcomas (n=23). RESULTS: On protein levels, high expression of VEGFR1 was
      detected immunohistochemically in 61%, VEGFR2 (KDR) in 11%, VEGFR3 in 64%, PDGFRA
      in 42% and PDGFRB in 73%. High expression of VEGFR1-3 and PDGFRB was
      significantly correlated with higher grading (G2 vs G3, p<0.05), and high VEGFR2
      was significantly correlated with decreased patients' survival (p<0.001).
      CONCLUSIONS: Tyrosine kinase receptors showed a distinct expression pattern in
      soft tissue sarcomas. High expression of VEGFR2 (KDR) is significantly associated
      with decreased patients' survival. High VEGFR 1-3 and PDGFRB are significantly
      correlated with higher tumor grading. Protein signatures might be evaluated
      before targeted therapy to give a rationale for an eligible personalized therapy.

PMID- 26298628
TI  - Fragile X Syndrome FMRP Co-localizes with Regulatory Targets PSD-95, GABA
      Receptors, CaMKIIalpha, and mGluR5 at Fiber Cell Membranes in the Eye Lens.
AB  - Fmr1 and FMRP underlie Fragile X Syndrome (FXS) and are linked with related
      autism spectrum disorders (ASD). Fmr1 also has an essential role in eye and lens
      development. Lenses express FMRP along with gamma-aminobutyric acid (GABA)
      receptors (GABARs), post-synaptic density protein 95 (PSD-95), Tyr-phosphatase
      STEP, CaMKIIalpha and Alzheimer's disease Abeta precursor protein, which are
      verified targets of FMRP regulation in neurons and outline major topics in
      FXS/ASD research. PSD-95 as well as CaMKIIalpha transcripts undergo
      polypryimidine tract binding protein dependent alternative splicing in lens,
      consistent with PSD-95 translation in lens. At least 13 GABAR subunits and
      GAD25/65/67 GABA metabolism enzymes are expressed in lenses beginning in
      embryonic development, matching neural development. Interestingly, GABAergic
      drugs (e.g. baclofen) studied as FXS/ASD therapeutics are shown to resolve
      developmental vision defects in experimental myopia. Here, we demonstrated that
      FMRP co-localizes at fiber cell membranes with PSD-95, GABAAdelta, GABAAbeta3,
      GABBR1, STEP, CaMKIIalpha, and mGluR5 in young adult lenses. GAD65 and GABA
      detection was greatest at the peri-nuclear lens region where fiber cell terminal
      differentiation occurs. These findings add to an extensive list of detailed
      parallels between fiber cell and neuron morphology and their lateral membrane
      spine/protrusions, also reflected in the shared expression of genes involved in
      the morphogenesis and function of these membrane structures, and shared use of
      associated regulatory mechanisms first described as distinguishing the neuronal
      phenotype. Future studies can determine if GABA levels currently studied as a
      FXS/ASD biomarker in the brain, and generated by GAD25/65/67 in a comparable cell
      environment in the lens, may be similarly responsive to Fmr1 mutation in lens.
      The present demonstration of FMRP and key regulatory targets in the lens
      identifies a potential for the lens to provide a new research venue, in the same
      individual, to inform about Fmr1/FMRP pathobiology in brain as well as lens. 

PMID- 26298630
TI  - Histopathological pattern of gonads in cases of sex abnormalities in dogs: An
      attempt of morphological evaluation involving potential for neoplasia.
AB  - Disturbances in sex differentiation (DSD - disorder of sexual development) may
      result from disturbances in sex chromosomes or a disturbed development of gonads,
      or from genotypic disturbances. The objective of this article is to describe the
      histological structure of gonads in dogs showing sexual disturbances and a case
      of a cancer resembling gonadoblastoma in one of the animals. Among the 10
      examined dogs with disturbances of sex development only a single case of a
      gonadoblastoma was observed. In animals with sex disturbances, similarly to
      humans, there exists a potential tendency for neoplastic lesions in dysgenetic
      gonads. As a rule, its frequency in population is confined due to the early
      procedure of castration of non-breeding dogs. In the present study dogs
      demonstrated phenotypical traits of bitches with developmental anomalies such as
      hyperplastic clitoris with vestigial os penis (baculum), or abnormalities in the
      location and structure of the vulva. The material for the study included canine
      gonads of various breeds, sampled from phenotypical bitches, aged 7 months to 4
      years - patients of the Department of Reproduction and Clinic of Farm Animals,
      Faculty of Veterinary Medicine, University of Environmental and Life Sciences in
      Wroclaw (Poland) in years 2006-2013. The organs were surgically removed from the
      abdomen and sent for histopathological examination for the purpose of determining
      their histological structure. The 10 examined cases of altered gonads included 6
      bilateral cases of testes (60%), 2 cases of bilateral ovotestis (20%), one case
      of co-manifestation of testis and ovotestis (10%), and a single case of a testis
      and a neoplastically altered gonad (gonadoblastoma) (10%). 

PMID- 26298631
TI  - Gut wall replacing type of gastrointestinal stromal tumor presenting as a
      perforation of the ileal diverticulum.
AB  - Gastrointestinal stromal tumors (GISTs) usually form a well-circumscribed mass.
      Very rarely, however, sporadic GISTs show gut-wall replacing growth, similar to
      the diffuse hyperplasia of interstitial cells of Cajal (ICC) observed in patients
      with neurofibromatosis type 1 (NF1) and hereditary GIST. Here we describe a
      patient with ileal perforation caused by this unusual type of GIST. An 82-year
      old man was admitted to the emergency department with sudden abdominal pain.
      Following a provisional diagnosis of perforation of Meckel's diverticulum, he
      underwent segmental resection of the small intestine. Macroscopic examination
      revealed a diverticulum-like structure 2.5cm in size near the site of mesenteric
      attachment of the ileum. Histological examination showed diffuse and nodular
      proliferation of spindle cells positive for c-KIT and CD34 that had replaced the
      muscularis propria of the small intestine. Mutational analyses of the lesions
      revealed monoclonality of proliferating cells with a somatic mutation in c-kit
      exon 11 (p.Leu576Pro). Gut-wall replacing type of GIST should be recognized as a
      specific type of GIST causing diverticulum-like structures of the
      gastrointestinal tract. 

PMID- 26298633
TI  - Signet ring cell carcinoma of the non-ampullary duodenum: A case report.
AB  - We describe a case of signet ring cell carcinoma of the non-ampullary duodenum in
      an 86-year-old woman. Endoscopic examination revealed a fungating lesion
      (Borrmann classification; type 2) on the anterior wall of the descending duodenum
      (second part). Pylorus-preserving pancreaticoduodenectomy and lymphadenectomy
      were performed. The tumor (pT3 and pN0) was predominantly composed of signet ring
      cells, characterized by a central, optically clear, globoid droplet of
      cytoplasmic mucin with an eccentrically placed nucleus. The cells were positive
      for periodic acid Schiff with diastase and Alcian blue pH 2.5. On
      immunohistochemical examination, MUC-5AC, MUC-2 and CDX2 were diffusely positive,
      and MUC-6 was negative in the tumor cells, which consisted of mixed gastric
      foveolar and intestinal phenotypes. Cytokeratin 7 was focally positive, but
      cytokeratin 20 was negative. Nuclear staining of p53 was diffusely and weakly
      positive. Signet ring cell carcinoma occurring in the non-ampullary duodenum
      might derive from duodenal goblet cells with MUC-5AC expression. 

PMID- 26298632
TI  - The clinicopathological and prognostic significance of CD24, CD44, CD133, ALDH1
      expressions in invasive ductal carcinoma of the breast: CD44/CD24 expression in
      breast cancer.
AB  - BACKGROUND: Recently, there are several studies about cancer stem cells (CSC),
      indicating that they are the cells that initiate the tumor, provide progression,
      metastasis and responsible for the aggressive tumor behavior. MATERIALS AND
      METHODS: The purpose of this study is to investigate the expressions of CD24,
      CD44, their different combinations, ALDH1 and CD133 in invasive ductal carcinoma.
      Their relationships with clinicopathologic parameters, such as tumor grade,
      lymphovascular invasion, tumor size, axillary lymph node involvement, stage,
      hormone receptors, HER2 expression, basal like tumors, triple negative status and
      prognosis were also investigated. Tissue microarray method was used to
      investigate immunohistochemical CD24, CD44, ALDH1 and CD133 expressions in 105
      invasive ductal carcinoma cases. RESULTS: CD133 expression was significantly
      associated with tumor size (p=0.023) and stage (p=0.009). CD133 expression was
      decreased in tumors with larger tumor size, higher stage and lymphovascular
      invasion. CD133 expression was positively correlated with CD44 (r=0.212, p=0.032)
      and CD44(+)/CD24(+) (r=0.202, p=0.040) expressions. CD44, CD24 and ALDH1
      expressions showed no significant relationship and correlation with
      clinicopathologic features. There was a significant relationship (p=0.048)
      between CD44(+)/CD24(-/low) phenotype and basal like tumors. EGFR expression was
      positively correlated with CD44(+)/CD24(-/low) phenotype (r=0.211, p=0.036).
      CONCLUSIONS: Basal like tumors are enriched for CSCs with CD44(+)/CD24(-/low)
      phenotype. CD133 can detect a different population of CSC in breast carcinoma.

PMID- 26298634
TI  - Knocking down the expression of TRA2beta inhibits the proliferation and migration
      of human glioma cells.
AB  - TRA2beta protein is encoded by the TRA2B gene (also called SFRS10) on human
      chromosome 3. It functions as a sequence-specific serine/arginine splicing factor
      that plays a role in mRNA processing, splicing patterns, and gene expression.
      Previous studies have demonstrated that TRA2beta is essential for normal mouse
      embryonic and brain development and has important roles in some cancers. However,
      the contribution of TRA2beta gene dysfunction to the pathology of human diseases,
      such as gliomas, has not been addressed. This study aimed to assess the
      expression and function of TRA2beta in human glioma. To analyze the expression
      levels of TRA2beta protein in glioma tissues, we performed immunohistochemical
      and Western blot analysis on human glioma tissues. The expression level of the
      TRA2beta protein was significantly higher in high-grade gliomas than in low-grade
      gliomas. A strongly positive correlation was observed between TRA2beta and Ki-67.
      More importantly, high expression of TRA2beta was associated with a poor outcome.
      In vitro, after the release of U87 cell lines from serum starvation, the
      expression of TRA2beta was upregulated, as well as PCNA and cyclin A. Knockdown
      of the TRA2beta gene resulted in suppression of the cell proliferation, cell
      cycle arrest during the G0/G1 phase, and a significant inhibition of cell
      migration. These results suggest that TRA2beta promotes glioma cell growth and
      migration, and could be a candidate for molecular targeting during gene therapy
      treatments of glioma. 

PMID- 26298635
TI  - Squamous morula formation in colorectal adenoma: Immunohistochemical and
      molecular analyses.
AB  - Little is known about the squamous morular component (SMC) in colorectal
      neoplasms because of its rarity. The aim of the present study is to elucidate the
      morphological, immunohistochemical and genetic characteristics of SMCs in
      colorectal adenomas. Five colorectal adenomas having SMCs were resected from five
      patients endoscopically. On immunohistochemical examination (four cases), all
      SMCs were positive for cytokeratin 5/6 in their cytoplasm and positive for beta
      catenin in their cytoplasm and nuclei. A nuclear positivity of p63 was detected
      in one SMC. All SMCs were negative for p53, chromogranin A, synaptophysin and
      NCAM. There was no Ki-67 expression in any of the SMCs. We detected none of
      mutations of beta-catenin, KRAS and BRAF by microdissection and polymerase chain
      reaction-direct sequence in any of the four examined SMCs. SMCs are a rare but
      problematic finding in colorectal adenomas. Using immunohistochemistry for beta
      catenin, cytokeratin 5/6, Ki-67, p53, chromogranin A, synaptophysin and NCAM can
      facilitate the diagnosis of these peculiar cell nests. 

PMID- 26298636
TI  - Multidisciplinary team review of best practices for collection and handling of
      blood cultures to determine effective interventions for increasing the yield of
      true-positive bacteremias, reducing contamination, and eliminating false-positive
      central line-associated bloodstream infections.
AB  - BACKGROUND: A literature search was conducted using keywords for articles
      published in English from January 1990 to March 2015. Using criteria related to
      blood culture collection and handling, the search yielded 101 articles.
      References used also included Microbiology Laboratory standards, guidelines, and
      textbook information. RESULTS: The literature identified diverse and complex
      issues surrounding blood culture practices, including the impact of false
      positive results, laboratory definition of contamination, effect on central line
      associated bloodstream infection (CLABSI) reporting, indications for collecting
      blood cultures, drawing from venipuncture sites versus intravascular catheters,
      selection of antiseptics, use of needleless connectors, inoculation of blood
      culture bottles, and optimizing program management in emergency departments,
      education, and implementation of bundled practice initiatives. CONCLUSION:
      Hospitals should optimize best practice in the collection, handling, and
      management of blood culture specimens, an often overlooked but essential
      component in providing optimal care of patients in all settings and populations,
      reducing financial burdens, and increasing the accuracy of reportable CLABSI.
      Although universal concepts exist in blood culture practices, some issues require
      further research to determine benefit. Institutions undertaking a review of their
      blood culture programs are encouraged to use a checklist that addresses elements
      that encompass the research contained in this review.

PMID- 26298637
TI  - Sesamolin enhances NK cell lysis activity by increasing the expression of NKG2D
      ligands on Burkitt's lymphoma cells.
AB  - Sesamolin and sesamin are representative lignans found in sesame seed. The
      present study was designed to demonstrate the anti-cancer activity of sesamolin
      achieved by increasing the expression level of NKG2D ligands on Raji cells, which
      are derived from Burkitt's lymphoma. The anti-cancer activity of sesamolin was
      also compared with that of sesamin. The cytolysis activity of NK cells against
      Raji was elevated by the pretreatment of sesamolin on Raji, but not by sesamin.
      We found that higher NKG2D ligand expression increased the sensitivity of
      sesamolin-treated Raji to NK cell lysis, resulting from a more active ERK
      signaling pathway. Our results provide evidence that targeting the ERK signaling
      pathway may enhance the antitumor activity of lignans and that there is a
      potential immunotherapeutic value for cancer treatment. 

PMID- 26298638
TI  - MOEPGA: A novel method to detect protein complexes in yeast protein-protein
      interaction networks based on MultiObjective Evolutionary Programming Genetic
      Algorithm.
AB  - The identification of protein complexes in protein-protein interaction (PPI)
      networks has greatly advanced our understanding of biological organisms. Existing
      computational methods to detect protein complexes are usually based on specific
      network topological properties of PPI networks. However, due to the inherent
      complexity of the network structures, the identification of protein complexes may
      not be fully addressed by using single network topological property. In this
      study, we propose a novel MultiObjective Evolutionary Programming Genetic
      Algorithm (MOEPGA) which integrates multiple network topological features to
      detect biologically meaningful protein complexes. Our approach first
      systematically analyzes the multiobjective problem in terms of identifying
      protein complexes from PPI networks, and then constructs the objective function
      of the iterative algorithm based on three common topological properties of
      protein complexes from the benchmark dataset, finally we describe our algorithm,
      which mainly consists of three steps, population initialization, subgraph
      mutation and subgraph selection operation. To show the utility of our method, we
      compared MOEPGA with several state-of-the-art algorithms on two yeast PPI
      datasets. The experiment results demonstrate that the proposed method can not
      only find more protein complexes but also achieve higher accuracy in terms of
      fscore. Moreover, our approach can cover a certain number of proteins in the
      input PPI network in terms of the normalized clustering score. Taken together,
      our method can serve as a powerful framework to detect protein complexes in yeast
      PPI networks, thereby facilitating the identification of the underlying
      biological functions. 

PMID- 26298639
TI  - Nanoplasmonic biochips for rapid label-free detection of imidacloprid pesticides
      with a smartphone.
AB  - The widespread and intensive use of neonicotinoid insecticides induces negative
      cascading effects on ecosystems. It is desirable to develop a portable sensitive
      sensing platform for on-site screening of high-risk pesticides. We combined an
      indirect competitive immunoassay, highly sensitive surface plasmon resonance
      (SPR) biochip and a simple portable imaging setup for label-free detection of
      imidacloprid pesticides. The SPR biochip consists of several capped nanoslit
      arrays with different periods which form a spectral image on the chip. The
      qualitative and semiquantitative analyses of pesticides can be directly observed
      from the spot shift on the chip. The precise semiquantitative analyses can be
      further completed by using image processing in a smartphone. We demonstrate
      simultaneous detection of four different concentrations of imidacloprid
      pesticides. The visual detection limit is about 1ppb, which is well below the
      maximum residue concentration permitted by law (20ppb). Compared to the one-step
      strip assay, the proposed chip is capable of performing semiquantitative analyses
      and multiple detection. Compared to the enzyme-linked immunosorbent assay, our
      method is label-free and requires simple washing steps and short reaction time.
      In addition, the label-free chip has a comparable sensitivity but wider working
      range than those labeling techniques. 

PMID- 26298640
TI  - Heart-on-a-chip based on stem cell biology.
AB  - Heart diseases are one of the main causes of death around the world. The great
      challenge for scientists is to develop new therapeutic methods for these types of
      ailments. Stem cells (SCs) therapy could be one of a promising technique used for
      renewal of cardiac cells and treatment of heart diseases. Conventional in vitro
      techniques utilized for investigation of heart regeneration do not mimic natural
      cardiac physiology. Lab-on-a-chip systems may be the solution which could allow
      the creation of a heart muscle model, enabling the growth of cardiac cells in
      conditions similar to in vivo conditions. Microsystems can be also used for
      differentiation of stem cells into heart cells, successfully. It will help better
      understand of proliferation and regeneration ability of these cells. In this
      review, we present Heart-on-a-chip systems based on cardiac cell culture and stem
      cell biology. This review begins with the description of the physiological
      environment and the functions of the heart. Next, we shortly described
      conventional techniques of stem cells differentiation into the cardiac cells.
      This review is mostly focused on describing Lab-on-a-chip systems for cardiac
      tissue engineering. Therefore, in the next part of this article, the microsystems
      for both cardiac cell culture and SCs differentiation into cardiac cells are
      described. The section about SCs differentiation into the heart cells is divided
      in sections describing biochemical, physical and mechanical stimulations.
      Finally, we outline present challenges and future research concerning Heart-on-a
      chip based on stem cell biology. 

PMID- 26298641
TI  - Luminol chemiluminescence biosensor for glycated hemoglobin (HbA1c) in human
      blood samples.
AB  - Luminol chemiluminescence (CL) biosensor based on boronic acid modified gold
      substrate has been developed for the determination of glycated hemoglobin (HbA1c)
      in human blood samples. In order to selectively capture HbA1c in sample, carboxy
      EG6-undecanethiol was self-assembled on a gold thin-film substrate, followed by
      covalent coupling of 3-aminophenyl boronic acid (3-APBA). The captured HbA1c
      containing four iron heme groups plays as a catalyst for luminol CL reaction in
      the presence of hydrogen peroxide, and thus the luminol CL response is linearly
      proportional to the amount of HbA1c captured on the biosensor surface. The
      present biosensor showed linear dynamic range of HbA1c from 2.5% to 17.0%, which
      well covers the clinically important concentration range. In addition, the
      present biosensor exhibited negligible response to interfering species such as
      hemoglobin, fructose, and sorbitol. The present HbA1c biosensor was applied to
      the determination of HbA1c in human blood samples and the results were well
      agreed with that obtained with a conventional method.

PMID- 26298642
TI  - Objective Assessment of Knot-Tying Proficiency With the Fundamentals of
      Arthroscopic Surgery Training Program Workstation and Knot Tester.
AB  - PURPOSE: To assess a new method for biomechanical assessment of arthroscopic
      knots and to establish proficiency benchmarks using the Fundamentals of
      Arthroscopic Surgery Training (FAST) Program workstation and knot tester.
      METHODS: The first study group included 20 faculty at an Arthroscopy Association
      of North America resident arthroscopy course (19.9 +/- 8.25 years in practice).
      The second group comprised 30 experienced surgeons attending an Arthroscopy
      Association of North America fall course (17.1 +/- 19.3 years in practice). The
      training group included 44 postgraduate year 4 or 5 orthopaedic residents in a
      randomized, prospective study of proficiency-based training, with 3 subgroups:
      group A, standard training (n = 14); group B, workstation practice (n = 14); and
      group C, proficiency-based progression using the knot tester (n = 16). Each
      subject tied 5 arthroscopic knots backed up by 3 reversed hitches on alternating
      posts. Knots were tied under video control around a metal mandrel through a
      cannula within an opaque dome (FAST workstation). Each suture loop was stressed
      statically at 15 lb for 15 seconds. A calibrated sizer measured loop expansion.
      Knot failure was defined as 3 mm of loop expansion or greater. RESULTS: In the
      faculty group, 24% of knots "failed" under load. Performance was inconsistent: 12
      faculty had all knots pass, whereas 2 had all knots fail. In the second group of
      practicing surgeons, 21% of the knots failed under load. Overall, 56 of 250 knots
      (22%) tied by experienced surgeons failed. For the postgraduate year 4 or 5
      residents, the aggregate knot failure rate was 26% for the 220 knots tied. Group
      C residents had an 11% knot failure rate (half the overall faculty rate, P =
      .013). CONCLUSIONS: The FAST workstation and knot tester offer a simple and
      reproducible educational approach for enhancement of arthroscopic knot-tying
      skills. Our data suggest that there is significant room for improvement in the
      quality and consistency of these important arthroscopic skills, even for
      experienced arthroscopic surgeons. LEVEL OF EVIDENCE: Level II, prospective
      comparative study.

PMID- 26298643
TI  - Potential Protective Effects of Chronic Anterior Thalamic Nucleus Stimulation on
      Hippocampal Neurons in Epileptic Monkeys.
AB  - BACKGROUND: Stimulation of the anterior nucleus of the thalamus (ANT) is
      effective in seizure reduction, but the mechanisms underlying the beneficial
      effects of ANT stimulation are unclear. OBJECTIVE: To assess the beneficial
      effects of ANT stimulation on hippocampal neurons of epileptic monkeys. METHODS:
      Chronic ANT stimulation was applied to kainic acid-induced epileptic monkeys.
      Behavioral seizures were continuously monitored. Immunohistochemical staining and
      western blot assays were performed to assess the hippocampal injury and the
      effects of ANT stimulation. RESULTS: The frequency of seizures was 42.8% lower in
      the stimulation group compared with the sham-stimulation group.
      Immunohistochemical staining and western blot analyses indicated that neuronal
      loss and apoptosis were less severe and that neurofilament synthesis was enhanced
      in the stimulation monkeys compared with the sham-stimulation group. These data
      showed that the hippocampal injury was less severe in monkeys in the stimulation
      group than in those in the sham-stimulation group. CONCLUSIONS: Our data suggest
      that chronic ANT stimulation may exert protective effects on hippocampal neurons
      and boost the regeneration of neuronal fibers. These effects may be closely
      related to the mechanisms of ANT stimulation in epilepsy treatment.

PMID- 26298645
TI  - Informal m-health: How are young people using mobile phones to bridge healthcare
      gaps in Sub-Saharan Africa?
AB  - The African communications 'revolution' has generated optimism that mobile phones
      might help overcome infrastructural barriers to healthcare provision in resource
      poor contexts. However, while formal m-health programmes remain limited in
      coverage and scope, young people are using mobile phones creatively and
      strategically in an attempt to secure effective healthcare. Drawing on
      qualitative and quantitative data collected in 2012-2014 from over 4500 young
      people (aged 8-25 y) in Ghana, Malawi and South Africa, this paper documents
      these practices and the new therapeutic opportunities they create, alongside the
      constraints, contingencies and risks. We argue that young people are endeavouring
      to lay claim to a digitally-mediated form of therapeutic citizenship, but that a
      lack of appropriate resources, social networks and skills ('digital capital'),
      combined with ongoing shortcomings in healthcare delivery, can compromise their
      ability to do this effectively. The paper concludes by offering tentative
      suggestions for remedying this situation. 

PMID- 26298644
TI  - Anxiety sensitivity mediates the association between post-traumatic stress
      symptom severity and interoceptive threat-related smoking abstinence expectancies
      among World Trade Center disaster-exposed smokers.
AB  - INTRODUCTION: Anxiety sensitivity (fear of internal anxiety-relevant bodily
      sensations) is an individual difference variable that is associated with the
      development and maintenance of posttraumatic stress disorder (PTSD) and is also
      involved in the maintenance/relapse of smoking. Abstinence expectancies are
      crucial to smoking maintenance, yet, past work has not explored how PTSD symptom
      severity and anxiety sensitivity contribute to them. METHOD: Participants were
      122 treatment-seeking daily smokers (36.1% female; Mage=49.2, SD=9.7; cigarettes
      per day: M=18.3, SD=15.2) who were exposed to the World Trade Center disaster on
      September 11, 2001 and responded to an advertisement for a clinical smoking
      cessation trial. The indirect effect of anxiety sensitivity was tested in terms
      of the effect of PTSD symptom severity on smoking abstinence expectancies (i.e.,
      anxiety sensitivity as a statistical mediator). RESULTS: PTSD symptom severity
      was positively associated with interoceptive threat-related smoking abstinence
      expectancies: expecting harmful consequences (beta=.33, p<.001) and somatic
      symptoms (beta=.26, p=.007). PTSD symptom severity was also significantly
      associated with anxiety sensitivity (beta=.27, p=.003). Anxiety sensitivity
      mediated the association between PTSD symptom severity and expectancies about the
      harmful consequences (beta=.09, CI95%=.02-.21; DeltaR(2)=.076) and somatic
      symptoms (beta=.11, CI95%=.02-.24; DeltaR(2)=.123) from smoking abstinence, with
      medium effect sizes (Kappa(2)=.08 and .10, respectively). CONCLUSIONS: These data
      document the role of PTSD symptoms in threat-based expectancies about smoking
      abstinence and suggest anxiety sensitivity may underlie the associations between
      PTSD symptom severity and abstinence expectancies.

PMID- 26298646
TI  - Individual and contextual correlates of physical activity among a clinical sample
      of United States Veterans.
AB  - RATIONALE: Veterans, especially those using U.S. Department of Veterans Affairs
      (VA) healthcare, have poorer health than the general population. In addition,
      Veterans using VA services are more likely than non-VA users to be physically
      inactive. Little is known about physical activity correlates among Veterans. To
      identify targets for health promotion interventions, understanding barriers to
      and facilitators of physical activity in this population is critical. METHODS:
      This study examined individual-, social-, and perceived neighborhood-level
      associations of meeting weekly physical activity recommendations (150 min/week of
      combined leisure and transportation activity) based on the International Physical
      Activity Questionnaire (IPAQ) among N = 717 patients from VA Puget Sound, Seattle
      Division using a mailed survey sent 2012-2013 (response rate = 40%). Independent
      associations were identified with direct estimation of relative risks using
      generalized linear models (dichotomous outcome), and linear regression
      (continuous outcome), including variables associated in bivariate tests (p <
      .05). RESULTS: Most participants were male, Caucasian, and unemployed, and had an
      annual income <=$40,000. Over two-thirds (69.9%) reported meeting physical
      activity recommendations. Fewer days of limitations due to physical or mental
      health (Relative Risk (RR) = 0.99 per day; 95% Confidence Interval (CI) = 0.98,
      0.99; p = .01), others doing physical activity with the Veteran (RR = 1.18; 95%
      CI = 1.04, 1.33; p = .01), receiving ideas from others regarding physical
      activity (RR = 1.14; 95% CI = 1.01, 1.29; p = .03) and better perceived
      neighborhood aesthetics (RR = 1.14; 95% CI = 1.06, 1.24; p = .001) were
      associated with meeting physical activity recommendations. Findings were
      comparable for total weekly physical activity, but lower depression symptom
      severity was also associated with increased physical activity. CONCLUSION: This
      study identified individual and contextual correlates of physical activity among
      VA-using Veterans. Targeting these factors will be important in promoting
      physical activity in order to address the disproportionate disease burden facing
      U.S. Veterans. Existing VA interventions targeting physical activity may need to
      be adapted to account for the influence of contextual factors.

PMID- 26298648
TI  - Novel conditions on exponential stability of a class of delayed neural networks
      with state-dependent switching.
AB  - This paper is concerned with the global exponential stability on a class of
      delayed neural networks with state-dependent switching. Under the novel
      conditions, some sufficient criteria ensuring exponential stability of the
      proposed system are obtained. In particular, the obtained conditions complement
      and improve earlier publications on conventional neural networks with continuous
      or discontinuous right-hand side. Numerical simulations are also presented to
      illustrate the effectiveness of the obtained results. 

PMID- 26298647
TI  - Effects of handrail hold and light touch on energetics, step parameters, and
      neuromuscular activity during walking after stroke.
AB  - BACKGROUND: Holding a handrail or using a cane may decrease the energy cost of
      walking in stroke survivors. However, the factors underlying this decrease have
      not yet been previously identified. The purpose of the current study was to fill
      this void by investigating the effect of physical support (through handrail hold)
      and/or somatosensory input (through light touch contact with a handrail) on
      energy cost and accompanying changes in both step parameters and neuromuscular
      activity. Elucidating these aspects may provide useful insights into gait
      recovery post stroke. METHODS: Fifteen stroke survivors participated in this
      study. Participants walked on a treadmill under three conditions: no handrail
      contact, light touch of the handrail, and firm handrail hold. During the trials
      we recorded oxygen consumption, center of pressure profiles, and bilateral
      activation of eight lower limb muscles. Effects of the three conditions on energy
      cost, step parameters and neuromuscular activation were compared statistically
      using conventional ANOVAs with repeated measures. In order to examine to which
      extent energy cost and step parameters/muscle activity are associated, we further
      employed a partial least squares regression analysis. RESULTS: Handrail hold
      resulted in a significant reduction in energy cost, whereas light touch contact
      did not. With handrail hold subjects took longer steps with smaller step width
      and improved step length symmetry, whereas light touch contact only resulted in a
      small but significant decrease in step width. The EMG analysis indicated a global
      drop in muscle activity, accompanied by an increased constancy in the timing of
      this activity, and a decreased co-activation with handrail hold, but not with
      light touch. The regression analysis revealed that increased stride time and
      length, improved step length symmetry, and decreased muscle activity were closely
      associated with the decreased energy cost during handrail hold. CONCLUSION:
      Handrail hold, but not light touch, altered step parameters and was accompanied
      by a global reduction in muscle activity, with improved timing constancy. This
      suggests that the use of a handrail allows for a more economic step pattern that
      requires less muscular activation without resulting in substantial neuromuscular
      re-organization. Handrail use may thus have beneficial effects on gait economy
      after stroke, which cannot be accomplished through enhanced somatosensory input
      alone.

PMID- 26298649
TI  - Evaluating psychiatric nursing competencies applied to emergency settings: A
      pilot role delineation study.
AB  - BACKGROUND: Despite increasing emergency department (ED) use for psychiatric
      emergencies, limited evidence exists to clearly identify the competencies
      necessary of emergency nurses to care for this population. PURPOSES: 1. To define
      the specialized skill and knowledge of emergency nurses by examining the
      frequency with which recommended psychiatric nursing competencies are performed
      in the ED setting. 2. To assess emergency nurses' rankings of importance and self
      efficacy related to recommended psychiatric nursing competencies in order to
      explore their relevance to emergency nursing. METHODS: Emergency nurses (n = 75)
      completed a survey ranking the frequency, importance and self-efficacy of 15
      psychiatric nursing competencies. Data analysis revealed competency relevance and
      regression analysis demonstrated factors that may contribute to self-efficacy.
      RESULTS: Nurses reported performing psychiatric competencies frequently (mean
      scores of 0.64 to 3.04). Importance rankings were highest (mean scores of 1.81 to
      3.67). Self-efficacy mean scores ranged from 0.89 to 3.47. Frequency and
      importance of activities predicted higher self-efficacy scores. Younger age and
      <5 years experience had negative impacts on self-efficacy scores. IMPLICATIONS:
      Emergency nurses perform psychiatric competencies often, and existing
      competencies appear applicable. As frequency and importance of competencies
      influence self-efficacy, practice and interventions to underscore the importance
      of competencies may improve self-efficacy. Younger and less experienced nurses
      might require more support.

PMID- 26298650
TI  - [Current practice of medicine].

PMID- 26298651
TI  - [Hearing rehabilitation in Treacher Collins Syndrome with bone anchored hearing
      aid].
AB  - OBJECTIVE: To describe a case of hearing rehabilitation with bone anchored
      hearing aid in a patient with Treacher Collins syndrome. CASE DESCRIPTION: 3
      years old patient, male, with Treacher Collins syndrome and severe complications
      due to the syndrome, mostly related to the upper airway and hearing. He had
      bilateral atresia of external auditory canals, and malformation of the pinna. The
      initial hearing rehabilitation was with bone vibration arch, but there was poor
      acceptance due the discomfort caused by skull compression. It was prescribed a
      model of bone-anchored hearing aid, in soft band format. The results were
      evaluated through behavioral hearing tests and questionnaires Meaningful Use of
      Speech Scale (Muss) and Infant-Toddler Meaningful Auditory Integration Scale (IT
      Mais). COMMENTS: The patient had a higher acceptance of the bone-anchored hearing
      aid compared to the traditional bone vibration arch. Audiological tests and the
      speech and auditory skills assessments also showed better communication and
      hearing outcomes. The bone-anchored hearing aid is a good option in hearing
      rehabilitation in this syndrome.

PMID- 26298652
TI  - [Socioeconomic, cultural and demographic maternal factors associated with dietary
      patterns of infants].
AB  - OBJECTIVE: To analyze dietary patterns of infants and its association with
      maternal socioeconomic, cultural, and demographic variables. METHODS: A cross
      sectional study was conducted with two groups of mothers of children up to 24
      months (n=202) living in the city of Maceio, Alagoas, Northeast Brazil. The case
      group consisted of mothers enrolled in a Family Health Unit. The comparison group
      consisted of mothers who took their children to two private pediatric offices of
      the city. Dietary intake was assessed using a qualitative and validated food
      frequency questionnaire (FFQ). The evaluation of the FFQ was performed by a
      method in which the overall rate of consumption frequency is converted into a
      score. RESULTS: Children of higher income families and mothers with better
      education level (control group) showed the highest median of consumption scores
      for fruits and vegetables (p<0.01) and meat, offal, and eggs (p<0.01), when
      compared with children of the case group. On the other hand, the median of
      consumption scores of manufactured goods was higher among children in the case
      group (p<0.01). CONCLUSIONS: Maternal socioeconomic status influenced the quality
      of food offered to the infant. In the case group, children up to 24 months
      already consumed industrial products instead of healthy foods on their menu.

PMID- 26298653
TI  - [Changes in physical fitness and nutritional status of schoolchildren in a period
      of 30 years (1980-2010)].
AB  - OBJECTIVE: To analyze and compare the changes in physical fitness according to
      the nutritional status and gender of schoolchildren during a period of 30 years
      (1980-2010). METHODS: Four cross-sectional evaluations were performed every 10
      years in a period of 30 years from 1978 to 1980 (baseline), 1988-1990 (10 years),
      1998-2000 (20 years) and 2008-2010 (30 years). The sample consisted of 1,291
      schoolchildren (188 in baseline, 307 in 10 years; 375 in 20 years; 421 in 30
      years) of 10 and 11 years old. The variables assessed were: body weight (kg),
      height (cm), upper limb strength (ULS; kg), lower limb strength (LLS; cm),
      agility (seconds) and velocity (seconds). Schoolchildren were classified as
      normal weight and overweight according to World Health Organization reference of
      body mass index for age and gender. Comparisons among periods applied ANOVA
      folled by Bonferroni test, with a significance level set at of p<0.01. Variation
      between baseline and 30 years was assessed by the percentage delta. Seven
      different percentile values were presented for each variable. RESULTS: In
      eutrophic boys and girls, mean values of ULS (-16.7%; -3.2%), agility (-1.5%; 
      1.6%) decreased significantly after 30 years (p<0,001). In the overweight boys
      and girls, only the average ULS (-15.5%; -12.5%) decreased significantly over
      time (p<0,001). After 30 years, the ULS percentile changed in boys. CONCLUSIONS:
      the decline in physical fitness was greater in schoolchildren with normal weight
      than in those with overweight.

PMID- 26298654
TI  - [Knowledge of pediatricians regarding physical activity in childhood and
      adolescence].
AB  - OBJECTIVE: To investigate the knowledge and guidance given by pediatricians
      regarding physical activity in childhood and adolescence. METHODS: A cross
      sectional study involving a convenience sample of pediatricians (n=210) who
      participated in a national pediatrics congress in 2013. Sociodemographic and
      professional data and data regarding habitual physical activity and
      pediatricians' knowledge and instructions for young people regarding physical
      activity were collected using a questionnaire. Absolute and relative frequencies
      and means and standard deviations were calculated. RESULTS: Most pediatricians
      were females, had graduated from medical school more than 15 years ago, and had
      residency in pediatrics. More than 70% of the participants reported to include
      physical activity guidance in their prescriptions. On the other hand,
      approximately two-thirds of the pediatricians incorrectly reported that children
      should not work out and less than 15% answered the question about physical
      activity barriers correctly. With respect to the two questions about physical
      activity to tackle obesity, incorrect answers were marked by more than 50% of the
      pediatricians. Most participants incorrectly reported that 30 minutes should be
      the minimum daily time of physical activity in young people. Less than 40% of the
      pediatricians correctly indicated the maximum time young people should spend in
      front of a screen. CONCLUSIONS: In general, the pediatricians reported that they
      recommend physical activity to their young patients, but specific knowledge of
      this topic was limited. Programs providing adequate information are needed.

PMID- 26298655
TI  - [Factors associated with abdominal obesity in children].
AB  - OBJECTIVE: To identify the association of dietary, socioeconomic factors,
      sedentary behaviors and maternal nutritional status with abdominal obesity in
      children. METHODS: A cross-sectional study with household-based survey, in 36
      randomly selected census tracts in the city of Santos/SP. 357 families were
      interviewed and questionnaires and anthropometric measurements were applied in
      mothers and their 3-0 years-old children. Assessment of abdominal obesity was
      made by maternal and child's waist circumference measurement; for classification
      used cut-off points proposed by World Health Organization (1998) and Taylor et
      al. (2000) were applied. The association between variables was performed by
      multiple logistic regression analysis. RESULTS: 30.5% of children had abdominal
      obesity. Associations with children's and maternal nutritional status and high
      socioeconomic status were shown in the univariate analysis. In the regression
      model, children's body mass index for age (OR=93.7; 95%CI 39.3-223.3), female
      gender (OR=4.1; 95%CI 1.8-9.3) and maternal abdominal obesity (OR=2.7; 95%CI 1.2
      6.0) were significantly associated with children's abdominal obesity, regardless
      of the socioeconomic status. CONCLUSIONS: Abdominal obesity in children seems to
      be associated with maternal nutritional status, other indicators of their own
      nutritional status and female gender. Intervention programs for control of
      childhood obesity and prevention of metabolic syndrome should consider the
      interaction of the nutritional status of mothers and their children.

PMID- 26298656
TI  - [Prevalence and factors associated with the co-occurrence of health risk
      behaviors in adolescents].
AB  - OBJECTIVE: To analyze the prevalence and factors associated with the co
      occurrence of health risk behaviors in adolescents. METHODS: A cross-sectional
      study was performed with a sample of high school students from state public
      schools in Pernambuco, Brazil (n=4,207, 14-19 years old). Data were obtained
      using a questionnaire. The co-occurrence of health risk behaviors was established
      based on the sum of five behavioral risk factors (low physical activity,
      sedentary behavior, low consumption of fruits/vegetables, alcohol consumption and
      tobacco use). The independent variables were gender, age group, time of day
      attending school, school size, maternal education, occupational status, skin
      color, geographic region and place of residence. Data were analyzed by ordinal
      logistic regression with proportional odds model. RESULTS: Approximately 10% of
      adolescents were not exposed to health risk behaviors, while 58.5% reported being
      exposed to at least two health risk behaviors simultaneously. There was a higher
      likelihood of co-occurrence of health risk behaviors among adolescents in the
      older age group, with intermediate maternal education (9-11 years of schooling),
      and who reported living in the driest (semi-arid) region of the state of
      Pernambuco. Adolescents who reported having a job and living in rural areas had a
      lower likelihood of co-occurrence of risk behaviors. CONCLUSIONS: The findings
      suggest a high prevalence of co-occurrence of health risk behaviors in this group
      of adolescents, with a higher chance in five subgroups (older age, intermediate
      maternal education, the ones that reported not working, those living in urban
      areas and in the driest region of the state).

PMID- 26298657
TI  - [Sleep in adolescents of different socioeconomic status: a systematic review].
AB  - OBJECTIVE: To analyze the sleep characteristics in adolescents from different
      socioeconomic levels. DATA SOURCE: Original studies found in the Medline/PubMed
      and SciELO databases without language and period restrictions that analyzed
      associations between sleep variables and socioeconomic indicators. The initial
      search resulted in 99 articles. After reading the titles and abstracts and
      following inclusion and exclusion criteria, 12 articles with outcomes that
      included associations between sleep variables (disorders, duration, quality) and
      socioeconomic status (ethnicity, family income, and social status) were analyzed.
      DATA SYNTHESIS: The studies associating sleep with socioeconomic variables are
      recent, published mainly after the year 2000. Half of the selected studies were
      performed with young Americans, and only one with Brazilian adolescents.
      Regarding ethnic differences, the studies do not have uniform conclusions. The
      main associations found were between sleep variables and family income or
      parental educational level, showing a trend among poor, low social status
      adolescents to manifest low duration, poor quality of sleeping patterns.
      CONCLUSIONS: The study found an association between socioeconomic indicators and
      quality of sleep in adolescents. Low socioeconomic status reflects a worse
      subjective perception of sleep quality, shorter duration, and greater daytime
      sleepiness. Considering the influence of sleep on physical and cognitive
      development and on the learning capacity of young individuals, the literature on
      the subject is scarce. There is a need for further research on sleep in different
      realities of the Brazilian population.

PMID- 26298658
TI  - [Acute urinary retention in a pre-school girl with constipation].
AB  - OBJECTIVE: To report a case of a preschool girl who developed acute urinary
      retention associated with constipation. CASE DESCRIPTION: A girl aged six years
      old presented a 24 hour history of inability to urinate. She was went twice to
      the emergency room during this period. In the first admission, 12 hours after the
      onset of the symptoms, she presented abdominal pain and acute urinary retention.
      After the drainage by urinary catheterization of 300 mL of clear urine, she
      presented relief of the symptoms and, as urinalysis had no change, the patient
      was discharged home. Twelve hours after the first visit, she returned to the
      emergency room complaining about the same symptoms. At physical examination,
      there was only a palpable and distended bladder up to the umbilicus with no other
      abnormalities. Again, a urinary catheterization was performed, which drained 450
      mL of clear urine, with immediate relief of the symptoms. Urinalysis and urine
      culture had no abnormalities. During the anamnesis, the diagnosis of constipation
      was considered and a plain abdominal radiography was performed, which identified
      large amount of feces throughout the colon (fecal retention). An enema with a 12%
      glycerin solution was prescribed for three days. During follow-up, the child used
      laxatives and dietary modifications, this contributed to the resolution of the
      constipation. There were no other episodes of urinary retention after 6 months of
      follow-up. COMMENTS: Acute urinary retention in children is a rare phenomenon and
      constipation should be considered as a cause.

PMID- 26298659
TI  - [Family presence during pediatric invasive procedures and resuscitation].

PMID- 26298660
TI  - [Family's presence in the pediatric emergency room: opinion of health's
      professionals].
AB  - OBJECTIVE: To learn the opinion of health professionals regarding the presence of
      family during pediatric emergency care. METHODS: Cross-sectional study, performed
      with 46 health professionals, members of the medical and nursing team of a
      pediatric emergency service. The data were collected via the application of a
      questionnaire composed by variables related to the opinion of professionals about
      the studied subject, in line with the professional category and the vocational
      training time, as well as invasive procedures during which the presence of family
      is authorized by the professionals. RESULTS: The medical staff and the
      professionals with shorter time after graduation (<10 years) were more favorable
      to the presence of family during emergency procedures. Regarding the complexity
      of the procedures, the nursing staff proved more favorable to the presence of
      family during less complex procedures-peripheral venous puncture and fluid sample
      whereas the consent of the medical staff was similar, regardless the performed
      procedure-peripheral venous puncture, fluid sample, intraosseous puncture,
      tracheal intubation and cardiopulmonary resuscitation. CONCLUSIONS: In order to
      allow the presence of family in the emergency room, it is necessary to sensitize
      health professionals, especially the nursing staff and the longer-term acting
      professionals, which are more resistant to allow the family to stay with the
      child during the emergency care.

PMID- 26298661
TI  - [Prevalence of excessive screen time and associated factors in adolescents].
AB  - OBJECTIVE: To determine the prevalence of excessive screen time and to analyze
      associated factors among adolescents. METHODS: This was a cross-sectional school
      based epidemiological study with 2,874 high school adolescents with age 14-19
      years (57.8% female) from public and private schools in the city of Joao Pessoa,
      PB, Northeast Brazil. Excessive screen time was defined as watching television
      and playing video games or using the computer for more than two hours per day.
      The associated factors analyzed were: sociodemographic (gender, age, economic
      class, and skin color), physical activity and nutritional status of adolescents.
      RESULTS: The prevalence of excessive screen time was 79.5% (95%CI: 78.1-81.1) and
      it was higher in males (84.3%) compared to females (76.1%; p<0,001). In
      multivariate analysis, adolescent males, aged 14-15 years old, of higher economic
      classes had higher chances of exposure to excessive screen time. The level of
      physical activity and nutritional status of adolescents were not associated with
      excessive screen time. CONCLUSIONS: The prevalence of excessive screen time was
      high and varied according to sociodemographic characteristics of adolescents. It
      is necessary to develop interventions to reduce the excessive screen time among
      adolescents, particularly in subgroups with higher exposure.

PMID- 26298662
TI  - [Perception of parents about second hand smoke on the health of their children:
      an ethnographic study].
AB  - OBJECTIVE: To analyze the perception of parents about secondhand smoking in their
      children's health. METHODS: Ethnographic qualitative and quantitative study. We
      sought the point of view and understanding of the parents that were active
      smokers in relation to environmental tobacco smoke (ETS) and secondhand smoking.
      Mothers and fathers who are active smokers and that live with their children from
      seven different public schools in the city of Anapolis, Midwest Brazil, were
      interviewed in the first semester of in a reserved room in the schools. A
      descriptive and qualitative analysis was carried out through the ethnography.
      RESULTS: 58 parents with an average time of smoking of 15.3 years and an average
      quantity of cigarettes smoked per day of 2 were interviewed. Among them, 59%
      didn't know what ETS was, and 60% stated knowing what a secondhand smoker was.
      However, when questioned about their children as secondhand smokers, 52% didn't
      consider them to be. Some parents knew some of the effects of secondhand smoking
      in the health of their children. However, the majority (52%) of them did not
      believe that their children would suffer any respiratory impairment or did not
      know about these impairments. CONCLUSIONS: Children were exposed to Environmental
      Tobacco Pollution in their residence if one considers parental duration of
      smoking and average of cigarettes smoked per day. There was a lack of knowledge
      of the parents about ETS, secondhand smoking and the evils that cigarettes could
      cause in the health of their children.

PMID- 26298664
TI  - Multiple Effect of APOE Genotype on Clinical and Neuroimaging Biomarkers Across
      Alzheimer's Disease Spectrum.
AB  - The apolipoprotein E epsilon4 (APOE epsilon4) allele is the most important
      genetic risk factor for Alzheimer's disease (AD); however, the underlying
      mechanisms responsible for it remain controversial. We used the Alzheimer's
      Disease Neuroimaging Initiative (ADNI) database to examine the influence of APOE
      epsilon4 dose on clinical and neuroimaging biomarkers across the AD spectrum
      (from cognitive normal to AD patients with severe cognitive impairment). A total
      of 1718 participants from the ADNI cohort were selected, and we evaluated the
      impact of epsilon4 dose on cerebrospinal fluid (CSF) levels' Abeta1-42 (Abeta1
      42), tau, and phosphorylated-tau (p-tau); cortical amyloid deposition
      (Florbetapir-PET-AV45); brain atrophy (MRI); brain metabolism (FDG-PET);
      hippocampal metabolism; and cognitive declines, through different cognitive
      subgroups. We found that (1) epsilon4 was associated with decreased CSF beta
      amyloid (Abeta1-42) and increased cerebral Abeta deposition across the AD
      spectrum; (2) increased CSF tau, P-tau and cerebral hypometabolism, hippocampal
      atrophy, and cognition decline were all associated with APOE epsilon4 in
      prodromal AD stage; (3) increased CSF tau, P-tau and cerebral hypometabolism
      appear to begin earlier than hippocampal atrophy and cognitive decline. We
      hypothesized that APOE epsilon4 increases cerebral amyloid-beta (Abeta)
      deposition in all the stages of AD development, and also influences Abeta
      initiated cascade of downstream neurodegenerative effects, thereby increasing the
      risk of AD.

PMID- 26298665
TI  - Regulation of Intracellular Structural Tension by Talin in the Axon Growth and
      Regeneration.
AB  - Intracellular tension is the most important characteristic of neuron polarization
      as well as the growth and regeneration of axons, which can be generated by motor
      proteins and conducted along the cytoskeleton. To better understand this process,
      we created Forster resonance energy transfer (FRET)-based tension probes that can
      be incorporated into microfilaments to provide a real-time measurement of forces
      in neuron cytoskeletons. We found that our probe could be used to assess the
      structural tension of neuron polarity. Nerve growth factor (NGF) upregulated
      structural forces, whereas the glial-scar inhibitors chondroitin sulfate
      proteoglycan (CSPG) and aggrecan weakened such forces. Notably, the tension
      across axons was distributed uniformly and remarkably stronger than that in the
      cell body in NGF-stimulated neurons. The mechanosensors talin/vinculin could
      antagonize the effect of glial-scar inhibitors via structural forces. However, E
      cadherin was closely associated with glial-scar inhibitor-induced downregulation
      of structural forces. Talin/vinculin was involved in the negative regulation of E
      cadherin transcription through the nuclear factor-kappa B pathway. Collectively,
      this study clarified the mechanism underlying intracellular tension in the growth
      and regeneration of axons which, conversely, can be regulated by talin and E
      cadherin.

PMID- 26298663
TI  - Streptozotocin Intracerebroventricular-Induced Neurotoxicity and Brain Insulin
      Resistance: a Therapeutic Intervention for Treatment of Sporadic Alzheimer's
      Disease (sAD)-Like Pathology.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder that is remarkably
      characterized by pathological hallmarks which include amyloid plaques,
      neurofibrillary tangles, neuronal loss, and progressive cognitive loss. Several
      well-known genetic mutations which are being used for the development of a
      transgenic model of AD lead to an early onset familial AD (fAD)-like condition.
      However, these settings are only reasons for a small percentage of the total AD
      cases. The large majorities of AD cases are considered as a sporadic in origin
      and are less influenced by a single mutation of a gene. The etiology of sporadic
      Alzheimer's disease (sAD) remains unclear, but numerous risk factors have been
      identified that increase the chance of developing AD. Among these risk factors
      are insulin desensitization/resistance state, oxidative stress,
      neuroinflammation, synapse dysfunction, tau hyperphosphorylation, and deposition
      of Abeta in the brain. Subsequently, these risk factors lead to development of
      sAD. However, the underlying molecular mechanism is not so clear. Streptozotocin
      (STZ) produces similar characteristic pathology of sAD such as altered glucose
      metabolism, insulin signaling, synaptic dysfunction, protein kinases such as
      protein kinase B/C, glycogen synthase-3beta (GSK-3beta) activation, tau
      hyperphosphorylation, Abeta deposition, and neuronal apoptosis. Further, STZ also
      leads to inhibition of Akt/PKB, insulin receptor (IR) signaling molecule, and
      insulin resistance in brain. These alterations mediated by STZ can be used to
      explore the underlying molecular and pathophysiological mechanism of AD
      (especially sAD) and their therapeutic intervention for drug development against
      AD pathology.

PMID- 26298666
TI  - LSD1-Mediated Demethylation of H3K4me2 Is Required for the Transition from Late
      Progenitor to Differentiated Mouse Rod Photoreceptor.
AB  - Epigenetic modifiers can work in concert with transcription factors to control
      the transition of cells from proliferating progenitors into quiescent terminally
      differentiated cells. This transition involves changes in histone methylation and
      one of the key regulators of this is the H3K4me2/1 histone demethylase LSD1.
      Here, we show that the highest expression of LSD1 occurs in postmitotic retinal
      cells during the peak period of rod photoreceptor differentiation.
      Pharmacological inhibition of LSD1 in retinal explants cultured from PN1 to PN8
      had three major effects. It prevented the normal decrease in expression of genes
      associated with progenitor function, it blocked rod photoreceptor development,
      and it increased expression of genes associated with other retinal cell types.
      The maintained expression of progenitor genes was associated with a maintained
      level of H3K4me2 over the gene and its promoter. Among the genes whose expression
      was maintained was Hes1, a repressor known to block rod photoreceptor
      development. The inhibition of rod photoreceptor gene expression occurred in
      spite of the normal expression of transcription factors CRX and NRL, and the
      normal accumulation of H3K4me2 marks over the promoter and gene body. We suggest
      that LSD1 acts in concert with a series of nuclear receptors to modify chromatin
      structure and repress progenitor genes as well as to inhibit ectopic patterns of
      gene expression in the differentiating postmitotic retinal cells.

PMID- 26298668
TI  - Evaluation of the toxic potential of calcium carbide in the third instar larvae
      of transgenic Drosophila melanogaster (hsp70-lacZ)Bg(9).
AB  - In the present study the toxic potential of calcium carbide (CaC2) was studied on
      the third instar larvae of transgenic Drosophila melanogaster (hsp70-lacZ)Bg(9).
      The third instar larvae were exposed to 2, 4, 8, 16 and 32*10(-3)g/ml of CaC2 in
      diet for 24h. The results reveal that the dose 2*10(-3)g/ml was not toxic but the
      remaining doses showed a dose dependent significant increase in the hsp70
      expression, beta-galactosidase activity, tissue damage, oxidative stress markers
      (lipid peroxidation and protein carbonyl content), glutathione-S-transferase
      activity, expression of Caspase 3 and 9, apoptotic index and DNA damage (midgut
      cells). A significant reduction as compared to control group in total protein,
      glutathione content and acetylcholinesterase activity was also observed. The
      Inductively Coupled Plasma Atomic Emission Spectroscopy analysis (ICPAES) reveals
      the presence of copper, iron, sodium, aluminium, manganese, calcium, nickel and
      mercury. The toxic effects of CaC2 in the present study may be attributed to the
      impurities present in it.

PMID- 26298667
TI  - Inhibitory Injury Signaling Represses Axon Regeneration After Dorsal Root Injury.
AB  - Following injury to peripheral axons, besides increased cyclic adenosine
      monophosphate (cAMP), the positive injury signals extracellular-signal-regulated
      kinase (ERK), c-Jun N-terminal kinase (JNK), and signal transducer and activator
      of transcription 3 (STAT-3) are locally activated and retrogradely transported to
      the cell body, where they induce a pro-regenerative program. Here, to further
      understand the importance of injury signaling for successful axon regeneration,
      we used dorsal root ganglia (DRG) neurons that have a central branch without
      regenerative capacity and a peripheral branch that regrows after lesion. Although
      injury to the DRG central branch (dorsal root injury (DRI)) activated ERK, JNK,
      and STAT-3 and increased cAMP levels, it did not elicit gain of intrinsic growth
      capacity nor the ability to overcome myelin inhibition, as occurred after
      peripheral branch injury (sciatic nerve injury (SNI)). Besides, gain of growth
      capacity after SNI was independent of ERK and cAMP. Antibody microarrays of
      dynein-immunoprecipitated axoplasm from rats with either DRI or SNI revealed a
      broad differential activation and transport of signals after each injury type and
      further supported that ERK, JNK, STAT-3, and cAMP signaling pathways are minor
      contributors to the differential intrinsic axon growth capacity of both injury
      models. Increased levels of inhibitory injury signals including GSK3beta and
      ROCKII were identified after DRI, not only in axons but also in DRG cell bodies.
      In summary, our work shows that activation and transport of positive injury
      signals are not sufficient to promote increased axon growth capacity and that
      differential modulation of inhibitory molecules may contribute to limited
      regenerative response.

PMID- 26298669
TI  - Dose reduction with iterative reconstruction in multi-detector CT: What is the
      impact on deformation of circular structures in phantom study?
AB  - OBJECTIVES: To evaluate the distortion of circular structures induced by the
      increased image noise related to dose reduction and to assess the effect of
      iterative reconstruction (IR). METHODS: MDCT acquisitions were performed with 120
      kVp for 200/100/60/40/20mAs with 100%/50%/30%/20%/10% of dose. Raw data were
      reconstructed by filtered back projection (FBP) and with two IR strengths. Image
      quality indices referred to water and acrylic were measured on a quality image
      phantom. Areas, perimeters, circularity were measured on the circular inserts of
      4.8, 7.9 and 11.1mm on a morphological phantom. RESULTS: Dose reduction resulted
      in increased image noise and in decreased signal to noise ratio and contrast to
      noise ratio. IR improved these indices for the same dose without affecting the
      signal (number CT) and spatial resolution (modulation transfer function). The
      values of area, perimeter and circularity were altered compared to the actual
      value and the inserts were visually deformed with the dose reduction. IR improved
      these three parameters. Image quality indices, areas, perimeters and circularity
      of inserts were similar between the acquisition at 100% of the dose in FBP, 50%
      in strength-3 and 30% in strength-5 with different curves of noise power
      spectrum. CONCLUSION: IR associated to 70% of dose reduction modifies the images
      smooth (NPS) but maintains adequate image quality indices without causing
      distortions of circular structures.

PMID- 26298670
TI  - Control of Escherichia coli and Listeria monocytogenes in suckling-lamb meat
      evaluated using microbial challenge tests.
AB  - Escherichia coli and Listeria monocytogenes microbial challenge tests were
      performed on fresh suckling-lamb meat. Hind leg slices were chilly stored under
      two modified atmosphere packaging (MAP) environments (A: 15%O2/60%CO2/25%N2, B:
      15%O2/30%CO2/55%N2) and vacuum packaging (V). Only E. coli was reduced between
      0.72-1.25 log cfu/g from day 1 to day 4 by the combined use of MAP/V, chilling
      storage and the growth of native lactic acid bacteria. However, L. monocytogenes
      was not inhibited by the application of V or MAP. Even do, in inoculated samples,
      this pathogen increased between 1.2-2.7 log cfu/g throughout the study.
      Consequently, a second experiment that combined the effects of MAP/V and a
      protective culture (Leuconostoc pseudomesenteroides PCK 18) against L.
      monocytogenes was designed. Two different levels of protective cultures were
      assayed (4 and 6 log cfu/g). Lc. pseudomesenteroides PCK 18 was able to control
      the growth of L. monocytogenes when the differences between them are higher than
      2 log cfu/g. Moreover, when high level of protective culture was used a
      significant reduction of L. monocytogenes counts were noticed in samples packaged
      in 60% of CO2 along the storage period, although sensory properties were also
      affected.

PMID- 26298671
TI  - Sequential recall of meaningful and arbitrary sequences by orangutans and human
      children: Does content matter?
AB  - Do visual cues such as size, color, and number facilitate sequential recall in
      orangutans and human children? In Experiment 1, children and adult orangutans
      solved two types of sequences, arbitrary (unrelated pictures) and meaningful
      (pictures varied along a spectrum according to the size, color, or number of
      items shown), in a touchscreen paradigm. It was found that visual cues did not
      increase the percentage of correct responses for either children or orangutans.
      In order to demonstrate that the failure to spontaneously seriate along these
      dimensions was not due to a general inability to perceive the dimensions nor to
      an inability to seriate items, in Experiment 2, orangutans were trained on one
      type of sequence and tested on novel sequences organized according to the same
      rule (i.e., pictures varied on the number spectrum only). The orangutans
      performed significantly better on novel meaningful sequences in this task than on
      novel arbitrary sequences. These results indicate that, while orangutans and
      human children share the ability to learn how to order items according to their
      size, color, or number, both orangutans and humans lack a cognitive propensity to
      spontaneously (i.e., without prior training or enculturation) order multiple
      items by size, color, or number. 

PMID- 26298672
TI  - Detecting Trends in Landuse and Landcover Change of Nech Sar National Park,
      Ethiopia.
AB  - Nech Sar National Park (NSNP) is one of the most important biodiversity centers
      in Ethiopia. In recent years, a widespread decline of the terrestrial ecosystems
      has been reported, yet to date there is no comprehensive assessment on
      degradation across the park. In this study, changes in landcover were analyzed
      using 30 m spatial resolution Landsat imagery. Interannual variations of
      normalized difference vegetation index (NDVI) were examined and compared with
      climatic variables. The result presented seven landcover classes and five of the
      seven landcover classes (forest, bush/shrubland, wooded grassland, woodland and
      grassland) were related to natural vegetation and two landcover types (cultivated
      land and area under encroaching plants) were direct results of anthropogenic
      alterations of the landscape. The forest, grassland, and wooded grassland are the
      most threatened habitat types. A considerable area of the grassland has been
      replaced by encroaching plants, prominently by Dichrostachys cinerea, Acacia
      mellifera, A. nilotica, A. oerfota, and A. seyal and is greatly affected by
      expansion of herbaceous plants, most commonly the species of the family Malvaceae
      which include Abutilon anglosomaliae, A.bidentatum and A.figarianu. Thus, changes
      in vegetation of NSNP may be attributed to (i) degradation of existing vegetation
      through deforestation and (ii) replacement of existing vegetation by encroaching
      plants. While limited in local meteorological station, NDVI analysis indicated
      that climate related changes did not have major effects on park vegetation
      degradation, which suggests anthropogenic impacts as a major driver of observed
      disturbances. 

PMID- 26298673
TI  - Clinical characteristics of bacteraemia caused by Lactobacillus spp. and
      antimicrobial susceptibilities of the isolates at a medical centre in Taiwan,
      2000-2014.
AB  - The clinical characteristics of 89 patients with Lactobacillus bacteraemia
      treated at a university-affiliated hospital in northern Taiwan during 2000-2014
      were retrospectively evaluated. Lactobacillus spp. were identified by 16S rRNA
      sequencing analysis and matrix-assisted laser desorption/ionisation time-of
      flight mass spectrometry (MALDI-TOF/MS). Antimicrobial susceptibilities of the
      isolates were determined by broth microdilution. The most commonly isolated
      species was Lactobacillus salivarius (n = 21), followed by Lactobacillus
      paracasei (n = 16) and Lactobacillus fermentum (n = 13). Excluding three isolates
      with lower 16S rRNA sequence similarity, MALDI-TOF/MS provided correct
      identification for 84.9% (73/86) of Lactobacillus isolates. Concordant
      identification was lowest for Lactobacillus casei (11%). The main infection foci
      were intra-abdominal infection (49%) and catheter-related bloodstream infection
      (17%). Only one-half of the patients received adequate antibiotic treatment
      during the bacteraemic episode. The majority of patients with Lactobacillus
      bacteraemia were immunocompromised. The 7-day and in-hospital mortality rates
      were 21% and 62%, respectively, and underlying malignancy was associated with a
      higher in-hospital mortality rate (odds ratio = 2.666). There were no significant
      differences in mortality (7-day, 14-day, 30-day and in-hospital) among patients
      with bacteraemia due to different Lactobacillus spp. Minimum inhibitory
      concentrations were highest for glycopeptides, cephalosporins and
      fluoroquinolones and were lowest for carbapenems and aminopenicillins.
      Lactobacillus bacteraemia was associated with a high mortality rate, and patient
      outcome was associated with underlying malignancy. MALDI-TOF/MS was able to
      accurately identify 84.9% of the Lactobacillus isolates, and L. salivarius was
      the predominant pathogen. The accuracy rate for identification of Lactobacillus
      spp. by MALDI-TOF/MS was lowest for L. casei.

PMID- 26298674
TI  - A longitudinal evaluation of the Resilient Families randomized trial to prevent
      early adolescent depressive symptoms.
AB  - This study aimed to evaluate whether an intervention prevented the development of
      depressive symptoms through the early years of secondary school (Grades 7 to 9 -
      mean ages 12.3 to 14.5 years) in Victoria, Australia. Twelve schools were
      randomized to a universal preventative intervention (including a student social
      relationship/emotional health curriculum, and parent/caregiver parenting
      education); 12 were randomized as control schools. Multivariate regression
      analyses used student self-report to predict depressive symptoms at 26-month
      follow-up (13-months after intervention completion) from baseline measures and
      intervention status (N = 2027). There was no overall intervention effect on
      depressive symptoms. However, intervention students with moderate symptoms whose
      parents attended parent education events had a significantly reduced risk of
      depressive symptoms at follow-up. Future evaluations of interventions of this
      type should investigate: therapeutic processes; methods to increase recruitment
      into effective parent education events; and the potential to target assistance to
      students with high depressive symptoms. 

PMID- 26298675
TI  - Examining the dimensional structure and nomological network of achievement goals
      in the Philippines.
AB  - The aim of this study was to test the cross-cultural validity of the 2 * 2
      achievement goal model in the Philippine context. The dimensional structure of
      the four achievement goals (mastery-approach, performance-approach, mastery
      avoidance, and performance-avoidance) and their associations with key learning
      outcomes were investigated. In Study 1, support for the dimensional structure of
      the 2 * 2 model was found. In Study 2, associations between achievement goals and
      learning outcomes such as engagement, disaffection, and achievement were
      investigated. Contrary to Western research, performance-avoidance was positively
      associated with adaptive outcomes and performance-approach goals were only weakly
      related to achievement. Cross-cultural implications are discussed. 

PMID- 26298676
TI  - Brief report: Examining children's disruptive behavior in the wake of trauma - A
      two-piece growth curve model before and after a school shooting.
AB  - School shootings may have serious negative impacts on children years after the
      event. Previous research suggests that children exposed to traumatic events
      experience heightened fear, anxiety, and feelings of vulnerability, but little
      research has examined potential aggressive and disruptive behavioral reactions.
      Utilizing a longitudinal dataset in which a local school shooting occurred during
      the course of data collection, this study sought to investigate whether the
      trajectory of disruptive behaviors was affected by the shooting. A two-piece
      growth curve model was used to examine the trajectory of disruptive behaviors
      during the pre-shooting years (i.e., piece one) and post-shooting years (i.e.,
      piece two). Results indicated that the two-piece growth curve model fit the data
      better than the one-piece model and that the school shooting precipitated a
      faster decline in aggressive behaviors. This study demonstrated a novel approach
      to examining effects of an unexpected traumatic event on behavioral trajectories
      using an existing longitudinal data set. 

PMID- 26298677
TI  - Chemometrics-assisted excitation-emission fluorescence analytical data for rapid
      and selective determination of optical brighteners in the presence of
      uncalibrated interferences.
AB  - This study describes a novel approach for the simultaneous determination of CBS-X
      and CXT as widely used optical brighteners in household detergent, by combining
      the advantage of the high sensitivity of molecular fluorescence, and the
      selectivity of second-order chemometric methods. The proposed method is assisted
      by second-order chemometric analyses employing the PARAFAC, SWATLD and APTLD that
      help us to determine CBS-X and CXT in laundry powders and environmental samples,
      through the unique decomposition of the three-way data array. Proposed method can
      provide the extraction of relative concentrations of the analytes, as well as the
      spectral profiles. This approach achieves the second-order advantage and in
      principle could be able to overcome the spectral uncalibrated interference
      problems in the determination of CBS-X and CXT at the ng g(-1) level. By spiking
      the known concentrations of these compounds to the real samples, the accuracy of
      the proposed methods was validated and recoveries of the spiked values were
      calculated. High recoveries (90.00%-113.33%) for the spiked laundry powders and
      real environmental samples indicate the present method successfully faces this
      complex challenge without the necessity of applying separation and
      preconcentration steps in environmental contaminations.

PMID- 26298678
TI  - Synthesis and spectroscopic characterization of fluorescent 4-aminoantipyrine
      analogues: Molecular docking and in vitro cytotoxicity studies.
AB  - Two substituted aromatic carbonyl compounds (compounds 1 and 2) of 4
      aminoantipyrine were synthesized by condensation of fluorine substituted benzoyl
      chlorides and 4-aminoantipyrine. The structures of synthesized derivatives were
      established on the basis of UV-Vis, IR, and Mass, (1)H, (13)C NMR and
      Fluorescence spectroscopy. Both compounds showed significant fluorescence
      emission and two broad emission bands were observed in the region at 340 nm and
      450 nm on excitation at 280 nm. Theoretically to prove that the molecule has
      anticancer activity against cervical cancer cells, the compounds were analyzed
      for molecular docking interactions with HPV16-E7 target protein by Glide
      protocol. Furthermore, 4-aminoantipyrine derivatives were evaluated for their in
      vitro cytotoxic activity against human cervical cancer cells (SiHa) by MTT assay.
      Compound 1 showed two fold higher activity (IC50=0.912 MUM) over compound 2, and
      its activity was similar to that of Pazopanib, suggesting that although the two
      compounds were chemically very similar the difference in substituent on the
      phenyl moiety caused changes in properties.

PMID- 26298679
TI  - Characterization of novel perylene diimides containing aromatic amino acid side
      chains.
AB  - Perylene diimide derivatives have attracted initial interest as industrial dyes.
      Recently, much attention has been focused on their strong pi-pi stacks resulting
      from the large PDI aromatic core. These PDI stacks have distinct optical
      properties, and provide informative models that could mimic light-harvesting
      systems and initial charge transfer typical of photosynthetic systems. The
      absorption property of PDI derivatives may be tuned from visible to near-infrared
      region by peripheral substitution. We have studied a new class of PDI derivatives
      with aryl substituents derived from the side chains of aromatic aminoacids
      (Tyrosine, Tryptophan and Phenylalanine). We have investigated their absorption
      and the fluorescence properties in a set of organic solvents and established
      their different tendencies to aggregate in solution despite their solubility.
      Most aggregation appears to be unordered. One PDI analogue (the one formed from
      Tyr) in Methanol, however, appears to form J-type aggregates. Based on our
      results the compounds appear to be promising for future investigations regarding
      the interaction of these dyes with biomolecules. 

PMID- 26298680
TI  - Mean centering of double divisor ratio spectra, a novel spectrophotometric method
      for analysis of ternary mixtures.
AB  - A novel spectrophotometric method was developed for determination of ternary
      mixtures without previous separation, showing significant advantages over
      conventional methods. The new method is based on mean centering of double divisor
      ratio spectra. The mathematical explanation of the procedure is illustrated. The
      method was evaluated by determination of model ternary mixture and by the
      determination of Amlodipine (AML), Aliskiren (ALI) and Hydrochlorothiazide (HCT)
      in laboratory prepared mixtures and in a commercial pharmaceutical preparation.
      For proper presentation of the advantages and applicability of the new method, a
      comparative study was established between the new mean centering of double
      divisor ratio spectra (MCDD) and two similar methods used for analysis of ternary
      mixtures, namely mean centering (MC) and double divisor of ratio spectra
      derivative spectrophotometry (DDRS-DS). The method was also compared with a
      reported one for analysis of the pharmaceutical preparation. The method was
      validated according to the ICH guidelines and accuracy, precision, repeatability
      and robustness were found to be within the acceptable limits. 

PMID- 26298681
TI  - A highly selective and sensitive fluorescent sensor for the rapid detection of
      Hg2+ based on phenylamine-oligothiophene derivative.
AB  - A fast-responsive fluorescent phenylamine-oligothiophene sensor 3TDDA was
      reported. This sensor exhibited highly selective and sensitive detection of
      Hg(2+) ion in aqueous solution (THF/CH3CN/H2O, 45/50/5, v/v) through fluorescence
      quenching. The detection was not affected by the coexistence of other competitive
      metal ions such as Na(+), K(+), Ag(+), Ca(2+), Fe(3+), Al(3+), Co(2+), Ni(2+),
      Zn(2+), Pb(2+), Cd(2+), Fe(2+) and Cr(3+). A stoichiometric ratio (1:1) of the
      sensor and Hg(2+) was determined by a Job's plot and mole-ratio curves. The
      binding of sensor 3TDDA and Hg(2+) was also chemically reversible with EDTA. The
      detection limit was calculated as low as 4.392*10(-7) M.

PMID- 26298682
TI  - B-type natriuretic peptide as a parameter for pulmonary hypertension in children.
      A systematic review.
AB  - Pulmonary hypertension (PH) is a life-threatening disease with a high mortality
      rate and a broad variety of underlying etiologies. The current golden standard
      for diagnosing PH and monitoring efficiency of treatment is right heart
      catheterization. As an alternative, serum biomarkers have been suggested. Cardiac
      troponin T (TnT), brain natriuretic peptide (BNP), and NT-proBNP seem the most
      potential. The aim of this systematic review was to evaluate the current
      literature on the prognostic value of these biomarkers in children with PH and
      their usefulness as a diagnostic tool. A systematic literature search yielded 14
      studies on patients <=18 years with proven PH with (NT-pro)BNP or TnT as primary
      outcome. TnT is suggested to be a promising biomarker, but its usefulness in
      clinical practice has not been proven. The levels of (NT-pro)BNP seemed to be
      reliable within one PH category, but differed significantly between categories.
      NT-proBNP showed a good correlation with mortality and might have a prognostic
      value. CONCLUSION: The lack of absolute levels makes (NT-pro)BNP unsuitable as a
      diagnostic marker, but in view of the relative changes, it could be used to
      monitor patients. Further investigation should explore differences in normal (NT
      pro)BNP levels between the different categories of PH. WHAT IS KNOWN: * Pulmonary
      hypertension is a life-threatening disease. Diagnosis can be challenging in
      children; the current diagnostic options-right heart catheterization and
      echocardiography-are invasive and/or investigator-dependent procedures. *
      Biomarkers could be useful in this context because they are investigator
      independent and easy to obtain through blood samples. Brain natriuretic peptide
      (BNP) and its N-terminal cleavage product (NT-proBNP) seem to be the most
      promising. The value of these biomarkers in the diagnostic approach of PH has
      already been investigated in adults, with promising results. Pediatric studies
      are still scarce. What is new: * The levels of BNP and NT-proBNP in pediatric
      patients differ strongly between the different categories of PH. Within the same
      category, the levels are more or less equal. * The relative changes could render
      them a prognostic marker in the follow-up of a certain individual patient. At
      this moment there is not enough evidence to rely on BNP or NT-proBNP in clinical
      treatment of patients with PH.

PMID- 26298683
TI  - The Influence of School-Based Health Centers on Adolescents' Youth Risk
      Behaviors.
AB  - INTRODUCTION: Youth risk behaviors that are developed during adolescence are
      likely to continue into adulthood, increasing chances of morbidity, mortality,
      and chronic health conditions. The Centers for Disease Control and Prevention
      identified six critical risk behaviors (unintentional injuries and violence,
      sexual behaviors leading to pregnancies and infections, alcohol and other drug
      use, tobacco use, poor dietary habits, and insufficient physical activities) and
      developed the Youth Risk Behavior Survey to monitor them. The purpose of this
      quantitative study was to investigate which health risk behaviors were affected
      by a new school-based health center (SBHC), using two urban school systems in the
      Mid-Atlantic region. METHOD: The Youth Risk Behavior Survey was administered at
      two schools in 2007 and 2011. Logistic regression was used to predict whether the
      dependent variables had changed based on the new SBHC. RESULTS: Overall, the new
      SBHC did not have a significant effect on the student's risk behaviors.
      DISCUSSION: Schools remain a critical part of adolescents' development, and
      access to SBHCs offers a safety net to students whose families may not have
      health insurance.

PMID- 26298684
TI  - Klatskin tumor: Diagnosis, preoperative evaluation and surgical considerations.
AB  - Hiliar cholangiocarcinoma is the most common type of cholangiocarcinoma, an
      represent around 10% of all hepatobiliary tumors. It is an aggressive malignancy,
      resectable in around 47% of the patients at diagnosis. Complete resection is the
      most effective and only potentially curative therapy, with a survival rate of
      less than 12 months in unresectable cases. Axial computerized tomography and
      magnetic resonance are the most useful image techniques to determine the surgical
      resectability. Clinically, jaundice and pruritus are the most common symptoms at
      diagnosis;preoperative biliary drainage is recommended using endoscopic
      retrograde cholangiography or percutaneous transhepatic cholangiography. Surgery
      using extended liver resections with an en bloc resection of the liver with
      vascular reconstruction is the technique with the highest survival. Complete
      resection with histologically negative resection margins (R0), nodal involvement
      and metastases are the most important prognostic factors. 

PMID- 26298686
TI  - Temporal changes in semantic and lexical access related to mild cognitive
      impairment.
AB  - BACKGROUND: It has been hypothesized that the deterioration in the ability to
      name famous people in normal aging and cognitive impairment is a continuum in
      which meaning-based representations and form-based representations are
      differentially impaired, with early impairments in lexical access but not in
      semantic access. AIMS: This hypothesis is tested in a follow-up study comparing
      the performance of fifty-six participants with amnestic mild cognitive impairment
      and forty-one control participants were assessed. METHOD: A lexical task was
      conducted involving recognition and naming of famous people from photographs.
      Proportional semantic and phonological access measures were calculated. RESULTS:
      Comparisons revealed significant differences between baseline and follow-up, with
      improvements in semantic access in the control group and decrements in
      phonological access in the group with amnestic mild cognitive impairment.
      Phonological access and reaction time measures were significantly and positively
      correlated, and semantic access and reaction time were significantly and
      negatively correlated. CONCLUSIONS: These results add evidence to the hypothesis
      that the decrease of processing resources is related to the increase of
      difficulties in lexical access throughout aging. Patterns of change must be
      replicated over longer periods of time.

PMID- 26298685
TI  - Endurance exercise and selective breeding for longevity extend Drosophila
      healthspan by overlapping mechanisms.
AB  - Endurance exercise has emerged as a powerful intervention that promotes healthy
      aging by maintaining the functional capacity of critical organ systems. In
      addition, long-term exercise reduces the incidence of age-related diseases in
      humans and in model organisms. Despite these evident benefits, the genetic
      pathways required for exercise interventions to achieve these effects are still
      relatively poorly understood. Here, we compare gene expression changes during
      endurance training in Drosophila melanogaster to gene expression changes during
      selective breeding for longevity. Microarrays indicate that 65% of gene
      expression changes found in flies selectively bred for longevity are also found
      in flies subjected to three weeks of exercise training. We find that both
      selective breeding and endurance training increase endurance, cardiac
      performance, running speed, flying height, and levels of autophagy in adipose
      tissue. Both interventions generally upregulate stress defense, folate
      metabolism, and lipase activity, while downregulating carbohydrate metabolism and
      odorant receptor expression. Several members of the methuselah-like (mthl) gene
      family are downregulated by both interventions. Knockdown of mthl-3 was
      sufficient to provide extension of negative geotaxis behavior, endurance and
      cardiac stress resistance. These results provide support for endurance exercise
      as a broadly acting anti-aging intervention and confirm that exercise training
      acts in part by targeting longevity assurance pathways. 

PMID- 26298687
TI  - Urinary tract infection after surgery for colorectal malignancy: risk factors and
      complications.
AB  - BACKGROUND: Over 4% of patients undergoing colorectal surgery develop
      postoperative urinary tract infection (UTI). METHODS: Using 2005 to 2012 American
      College of Surgeons National Surgical Quality Improvement Program data for 47,781
      patients, we examined independent risk factors and complications associated with
      UTI using multivariate logistic regression. RESULTS: Independent predictors of
      UTI included female sex (odds ratio [OR] 1.705, 95% confidence interval [CI]
      1.508 to 1.928), open procedure (OR 1.419, 95% CI 1.240 to 1.624), rectal
      procedure (OR 1.267, 95% CI 1.105 to 1.453), age greater than 65 years (OR 1.322,
      95% CI 1.151 to 1.519), nonindependent functional status (OR 1.609, 95% CI 1.299
      to 1.993), steroid use (OR 1.524, 95% CI 1.116 to 2.080), higher anesthesia
      class, and longer operative time. Patients with UTI had longer hospital stays (7
      vs 12 days), higher reoperation rates (11.9% vs 5.1%), and higher 30-day
      mortality (3.3% vs 1.7%). Postoperative UTI correlated with other complications,
      including sepsis, surgical site infections, and pulmonary embolism (P < .001).
      CONCLUSIONS: Postoperative UTI in colorectal surgery patients correlates with
      increased morbidity and mortality. Patients who contract postoperative UTI may be
      more likely to develop multiple complications.

PMID- 26298688
TI  - Hydrogen-bonding-mediated synthesis of atomically thin TiO2 films with exposed
      (001) facets and applications in fast lithium insertion/extraction.
AB  - Ultrathin two-dimensional (2D) crystalline materials show high specific surface
      area (SA) of high energy (HE) facets, imparting a significant improvement in
      their performances. Herein we report a novel route to synthesize TiO2 nanofilms
      (NFs) with atomic thickness (<2.0 nm) through a solvothermal reaction mediated by
      the hydrogen-bonding networks constructed by hydroquinone (HQ). The resultant
      TiO2 NFs have nearly 100 % exposed (001) facets and give an extremely high SA up
      to 487 m(2)  g(-1) . The synergistic effect of HQ and choline chloride plays a
      vital role in the formation of TiO2 NFs and in the exposure of HE (001) facets.
      Because of its ultrathin feature and exposed (001) facet, the N2 -annealled TiO2
      NFs showed fast kinetics of lithium insertion/extraction, demonstrating
      foreseeable applications in the energy storage. 

PMID- 26298689
TI  - Does the Animal Fun program improve social-emotional and behavioural outcomes in
      children aged 4-6 years?
AB  - Animal Fun was designed to enhance motor and social development in young
      children. Its efficacy in improving motor skills was presented previously using a
      randomised controlled trial and a multivariate nested cohort design. Based on the
      Environmental Stress Hypothesis, it was argued that the program would also result
      in positive mental health outcomes, investigated in the current study. Pre
      intervention scores were recorded for 511 children aged 4.83-6.17 years (M=5.42,
      SD=.30). Intervention and control groups were compared 6 months following
      intervention, and again in their first school year. Changes in teacher-rated
      prosocial behaviour and total difficulties were assessed using the Strengths and
      Difficulties Questionnaire, and data analysed using Generalised Linear Mixed
      Models. There was a significant improvement in prosocial behaviour of children in
      the intervention group six months after initial testing, which remained at 18
      month follow-up. Total difficulties decreased at 6 months for the intervention
      group, with no change at 18 months. This effect was present only for the
      hyperactivity/inattention subscale. The only significant change for the control
      group was an increase in hyperactivity/inattention scores from pre-intervention
      to 18-month follow-up. The Animal Fun program appears to be effective in
      improving social and behavioural outcomes.

PMID- 26298690
TI  - Direct photolysis of MeO-PBDEs in water and methanol: focusing on cyclization
      product MeO-PBDFs.
AB  - Polybrominated diphenyl ethers (PBDEs) and hydroxylated PBDEs can transform into
      polybrominated dibenzofurans (PBDFs) via photocyclization. However, it is unclear
      whether methoxylated PBDEs (MeO-PBDEs) can photocyclize to form MeO-PBDFs. In
      this study, 5-MeO-BDE-47, 5'-MeO-BDE-99 and 6-MeO-BDE-85 were selected as models
      to investigate their direct photolysis, especially photocyclization in two
      solvent environments (water and methanol) using simulated photochemical
      experiments and density functional theory (DFT) calculations. The experimental
      results showed that MeO-PBDEs had faster direct photolysis reactions and higher
      quantum yields in methanol, and MeO-PBDFs could only be formed in a methanol
      solution of 5-MeO-BDE-47. The DFT results indicated that the lowest excited
      triplet state MeO-PBDEs can form dibenzofurans via direct cyclization pathways.
      Intra-annular H-elimination was found to be the rate-determining step for most
      cyclization pathways with high reaction barriers (?19.7kcal/mol), while 5-MeO-BDE
      47 was found to have a distinct pathway for which the rate-determining step is
      ring closure with a low barrier (13.8kcal/mol) in a methanol environment. For
      this pathway, H-elimination assisted by Br cleaved from an ortho-C-Br bond was
      observed with a 2.0kcal/mol barrier. Thus, the DFT results reasonably explained
      the experimental findings, and the photocyclization of MeO-PBDEs depended on the
      specific Br-substitution patterns and specific effects of the environmental
      media.

PMID- 26298693
TI  - Out-of-pocket payments for health care in Serbia.
AB  - BACKGROUND: This study focuses on out-of-pocket payments for health care in
      Serbia. In contrast to previous studies, we distinguish three types of out-of
      pocket patient payments: official co-payments, informal (under-the-table)
      payments and payments for "bought and brought goods" (i.e. payments for health
      care goods brought by the patient to the health care facility). METHODS: We
      analyse the probability and intensity of three different types of out-of-pocket
      patient payments in the public health care sector in Serbia and their
      distribution among different population groups. We use data from the Serbian
      Living Standard Measures Study carried out in 2007. Out-of-pocket patients
      payments for both outpatient and inpatient health care are included. The data are
      analysed using regression analysis. RESULTS: The majority of health care users
      report official co-payments (84.7%) and payments for "bought and brought goods"
      (61.1%), whereas only 5.7% health care users declare that they have paid
      informally. Regarding the regression results, users with an income below the
      poverty line, those from rural areas and who are not married are more likely to
      report payments for "bought and brought goods, while young and more educated
      users are more likely to report informal patient payments. CONCLUSION: Overall,
      the three types of out-of-pocket payments are not correlated. Payments for
      "bought and brought goods" take the highest share of the total annual household
      budget. Serbian policymakers need to consider different strategies to deal with
      informal payments and to eliminate the practice of "bought and brought goods".

PMID- 26298691
TI  - Cortisol covariation within parents of young children: Moderation by relationship
      aggression.
AB  - Covariation in diurnal cortisol has been observed in several studies of
      cohabiting couples. In two such studies (Liu et al., 2013; Saxbe and Repetti,
      2010), relationship distress was associated with stronger within-couple
      correlations, suggesting that couples' physiological linkage with each other may
      indicate problematic dyadic functioning. Although intimate partner aggression has
      been associated with dysregulation in women's diurnal cortisol, it has not yet
      been tested as a moderator of within-couple covariation. This study reports on a
      diverse sample of 122 parents who sampled salivary cortisol on matched days for
      two years following the birth of an infant. Partners showed strong positive
      cortisol covariation. In couples with higher levels of partner-perpetrated
      aggression reported by women at one year postpartum, both women and men had a
      flatter diurnal decrease in cortisol and stronger correlations with partners'
      cortisol sampled at the same timepoints. In other words, relationship aggression
      was linked both with indices of suboptimal cortisol rhythms in both members of
      the couples and with stronger within-couple covariation coefficients. These
      results persisted when relationship satisfaction and demographic covariates were
      included in the model. During some of the sampling days, some women were pregnant
      with a subsequent child, but pregnancy did not significantly moderate cortisol
      levels or within-couple covariation. The findings suggest that couples
      experiencing relationship aggression have both suboptimal neuroendocrine profiles
      and stronger covariation. Cortisol covariation is an understudied phenomenon with
      potential implications for couples' relationship functioning and physical health.

PMID- 26298692
TI  - Does white matter structure or hippocampal volume mediate associations between
      cortisol and cognitive ageing?
AB  - Elevated glucocorticoid (GC) levels putatively damage specific brain regions,
      which in turn may accelerate cognitive ageing. However, many studies are cross
      sectional or have relatively short follow-up periods, making it difficult to
      relate GCs directly to changes in cognitive ability with increasing age.
      Moreover, studies combining endocrine, MRI and cognitive variables are scarce,
      measurement methods vary considerably, and formal tests of the underlying causal
      hypothesis (cortisol->brain->cognition) are absent. In this study, 90 men, aged
      73 years, provided measures of fluid intelligence, processing speed and memory,
      diurnal and reactive salivary cortisol and two measures of white matter (WM)
      structure (WM hyperintensity volume from structural MRI and mean diffusivity
      averaged across 12 major tracts from diffusion tensor MRI), hippocampal volume,
      and also cognitive ability at age 11. We tested whether negative relationships
      between cognitive ageing differences (over more than 60 years) and salivary
      cortisol were significantly mediated by WM and hippocampal volume. Significant
      associations between reactive cortisol at 73 and cognitive ageing differences
      between 11 and 73 (r=-.28 to -.36, p<.05) were partially mediated by both WM
      structural measures, but not hippocampal volume. Cortisol-WM relationships were
      modest, as was the degree to which WM structure attenuated cortisol-cognition
      associations (<15%). These data support the hypothesis that GCs contribute to
      cognitive ageing differences from childhood to the early 70s, partly via brain WM
      structure. 

PMID- 26298694
TI  - Clinical application of a novel developed pressure bladder indicator in lumbar
      epidural puncture.
AB  - STUDY OBJECTIVE: A novel pressure bladder indicator was developed, and this study
      aimed to evaluate the clinical application of the pressure bladder indicator by
      measuring the epidural space pressure and bladder working pressure on patients
      undergoing lumbar epidural puncture. DESIGN: Randomized, prospective, double
      blinded study PATIENTS: 130 patients SETTING: The Second Hospital of Shandong
      University INTERVENTIONS: In this study, 60 patients undergoing surgical
      procedures under lumbar epidural anesthesia were enrolled to detect epidural
      pressure, and other 70 patients who were undergoing lumbar epidural anesthesia or
      combined spinal-epidural anesthesia were enrolled to evaluate the pressure
      bladder indicator. MEASUREMENTS: After successful breakthrough of ligamentum
      flavum by traditional methods, a pressure transducer was connected to an epidural
      needle tail and a monitor to measure the epidural pressure at L1-L5 in 60
      patients. The working pressure of the bladder was also measured by a transducer.
      Then lumbar epidural puncture was performed with the pressure bladder indicator
      in other 70 patients. MAIN RESULTS: The lumbar epidural pressure of the 60
      patients was 9.8 +/- 4.3 mm Hg, and the bladder working pressure of the pressure
      bladder indicator was 122 +/- 15 mm Hg. All these 70 patients were confirmed with
      successful bladder indication and lumbar epidural puncture. Thus, the coincidence
      ratio was 100%. CONCLUSIONS: The novel developed pressure bladder indicator was a
      reliable and useful technique to conduct successful lumbar epidural puncture.

PMID- 26298695
TI  - Thermotolerance of apple tree leaves probed by chlorophyll a fluorescence and
      modulated 820 nm reflection during seasonal shift.
AB  - During the seasonal shift from June to August, air temperatures increase. To
      explore how apple trees improve their thermotolerance during this shift, we
      examined the photochemical reaction capacity of apple tree leaves by simultaneous
      measurement of prompt chlorophyll fluorescence, delayed chlorophyll fluorescence,
      and modulated 820 nm reflection at varying temperatures. It was found that the
      reaction centers and antennae of photosystem II (PSII) and photosystem I (PSI),
      the donor side of PSII, the electron transfer capacity from QA to QB, and the
      reoxidation capacity of plastoquinol were all sensitive to heat stress,
      particularly in June. As the season shifted, apple tree leaves improved in
      thermotolerance. Interestingly, the acclimation to seasonal shift enhanced the
      thermotolerance of PSII and PSI reaction centers more than that of their
      antennae, and the activity of PSII more than that of PSI. This may be a strategy
      for plant adaptation to changes in environmental temperatures. In addition,
      results from prompt and delayed fluorescence, as well as modulated 820 nm
      reflection corroborate each other. We suggest that the simultaneous measurement
      of the three independent signals may provide more information on thermal
      acclimation mechanisms of photochemical reactions in plant leaves.

PMID- 26298696
TI  - The action spectrum of Photosystem II photoinactivation in visible light.
AB  - Photosynthesis is always accompanied by light induced damage to the Photosystem
      II (PSII) which is compensated by its subsequent repair. Photoinhibition of PSII
      is a complex process, balancing between photoinactivation, protective and repair
      mechanisms. Current understanding of photoinactivation is limited with competing
      hypotheses where the photosensitiser is either photosynthetic pigments or the
      Mn4CaO5 cluster itself, with little consensus on the mechanisms and consequences
      of PSII photoinactivation. The mechanism of photoinactivation should be reflected
      in the action spectrum of PSII photoinactivation, but there is a great diversity
      of the action spectra reported thus far. The only consensus is that PSII
      photoinactivation is greatest in the UV region of the electromagnetic spectrum.
      In this review, the authors revisit the methods, technical constraints and the
      different action spectra of PSII photoinactivation reported to date and compare
      them against the diverse mechanisms proposed. Upon critical examination of the
      reported action spectra, a hybrid mechanism of photoinactivation, sensitised by
      both photosynthetic pigments and the Mn4CaO5 appears to be the most plausible
      rationalisation. 

PMID- 26298697
TI  - Modeling microbial growth and dynamics.
AB  - Modeling has become an important tool for widening our understanding of microbial
      growth in the context of applied microbiology and related to such processes as
      safe food production, wastewater treatment, bioremediation, or microbe-mediated
      mining. Various modeling techniques, such as primary, secondary and tertiary
      mathematical models, phenomenological models, mechanistic or kinetic models,
      reactive transport models, Bayesian network models, artificial neural networks,
      as well as agent-, individual-, and particle-based models have been applied to
      model microbial growth and activity in many applied fields. In this mini-review,
      we summarize the basic concepts of these models using examples and applications
      from food safety and wastewater treatment systems. We further review recent
      developments in other applied fields focusing on models that explicitly include
      spatial relationships. Using these examples, we point out the conceptual
      similarities across fields of application and encourage the combined use of
      different modeling techniques in hybrid models as well as their cross
      disciplinary exchange. For instance, pattern-oriented modeling has its origin in
      ecology but may be employed to parameterize microbial growth models when
      experimental data are scarce. Models could also be used as virtual laboratories
      to optimize experimental design analogous to the virtual ecologist approach.
      Future microbial growth models will likely become more complex to benefit from
      the rich toolbox that is now available to microbial growth modelers. 

PMID- 26298698
TI  - Analysis of the intestinal microbial community structure of healthy and long
      living elderly residents in Gaotian Village of Liuyang City.
AB  - Gaotian, one typical conservative village in rural area of South China, is
      differentiated from other adjacent village for its longevity and health situation
      of residents. To ascertain the difference of intestinal microbial community
      between Gaotian and other region, high-throughput sequencing and systematical
      bioinformation analyses was adopted to compare 21 samples in long life group with
      28 in control group. The alpha diversity showed that the diversity of species of
      intestinal flora of Gaotian villagers was higher than that of control group,
      while the beta diversity showed that the similarity of intestinal flora for
      Gaotian residents was also much higher than that of control group. OTU cluster
      analysis and Venn diagram showed that the intestinal microbial community of
      Gaotian villagers is different from that of control group. To quantitatively
      compare the main flora constitution in all samples, real-time PCR was performed,
      and the results showed that the biomass of Enterococcus, Lactobacillus,
      Enterobacteriaceae, Clostridium perfringens, and Bacteroides of Gaotian villages
      is generally significantly higher than that of control group. Remarkably, some
      special species, i.e., Methanobacterium, Butyricimonas, Deinococcus, and
      Streptococcaceae, have been found in Gaotian villagers. Overall, this study lays
      a preparatory basis for exploration of the resources of special species from
      healthy and long-living elderly Gaotian villagers and for proposal of a
      hypothesis, namely, the diversity in intestinal flora of Gaotian might contribute
      to the longevity and health of local residents. Further study should be focused
      on screening and functional evaluation of the special species in the long-life
      residents.

PMID- 26298699
TI  - Study of bioleaching under different hydraulic retention time for enhancing the
      dewaterability of digestate.
AB  - Dewatering of kitchen waste digestate is a key problem to solve so as to increase
      the application of kitchen waste after anaerobic digestion. In this study, the
      effects of bioleaching under different hydraulic retention time (HRT = 2, 2.5,
      and 3 days) on dewaterability of kitchen waste digestate were evaluated. A 12
      stage plug flow bioreactor with 180 L working volume was used for digestate
      bioleaching. The bioleached digestate under different HRTs were collected and
      dewatered by plate-and-frame filter press. The results showed that the moisture
      contents of digestate cakes were 67.87 % at 2 days of HRT, 58.06 % at 2.5 days of
      HRT, and 54.45 % at 3 days of HRT, respectively, indicating the longer the HRT,
      the lower the moisture content of filter cake. Balanced between the cost and
      practical need, 2.5 days can be used as the HRT in engineering application. Under
      the condition of HRT of 2.5 days, the pH, specific resistance to filtration
      (SRF), capillary suction time (CST), and sedimentation rate of digestate changed
      from the initial values of 8.08, 210.6 s, 23.4 * 10(12) m kg(-1) and 10 % to
      3.21, 32.7 s, 2.44 * 10(12) m kg(-1) and 76.8 %, respectively. Based on the
      observations above, the authors conclude that bioleaching technology is an
      effective method to enhance digestate dewaterability and reduce the cost of
      subsequent reutilization. 

PMID- 26298700
TI  - Molecular mechanism involved in the response to hydrogen peroxide stress in
      Acinetobacter oleivorans DR1.
AB  - Two-dimensional gel electrophoresis was conducted to investigate the effect of
      H2O2 on whole protein expression in Acinetobacter oleivorans DR1. Functional
      classification of 13 upregulated proteins using MALDI-TOF mass spectrometry
      showed relationships with oxidative stress, energy production and conversion,
      nucleotide and amino acid metabolism, membrane-related, ion transport, and
      chaperone-related functions. Alignment of OxyR-binding regions from Pseudomonas
      aeruginosa and Escherichia coli with promoters of identified proteins revealed
      that only ahpC, ahpF, and trxB (thioredoxin-disulfide reductase) genes, along
      with a newly found oprC (putative outer membrane receptor protein) gene, have
      OxyR-binding sites. The oxyR and ahpC mutants were more sensitive to H2O2 and
      showed growth defects in both nutritional and n-hexadecane-amended media. Four
      catalases present in the genome of A. oleivorans DR1 were not detected, which led
      us to confirm the expression and activity of those catalases in the presence of
      H2O2. The expression patterns of the four catalase genes differed at different
      concentrations of H2O2. Interestingly, the promoters of both known OxyR
      controlled katG gene (AOLE_17390) and putative small catalase gene (AOLE_09800)
      have OxyR-binding sites. Gel-shift assay confirmed OxyR binding to the promoter
      regions of newly identified OxyR-controlled genes encoding OprC and a putative
      catalase. Hierarchical expression and OxyR-binding of several OxyR-controlled
      genes suggested that concentration is an important factor in inducing the set of
      genes under H2O2 stress. 

PMID- 26298701
TI  - The PhoP transcription factor negatively regulates avermectin biosynthesis in
      Streptomyces avermitilis.
AB  - Bacteria sense and respond to the stress of phosphate limitation, anticipating Pi
      deletion/starvation via the two-component PhoR-PhoP system. The role of the
      response regulator PhoP in primary metabolism and avermectin biosynthesis in
      Streptomyces avermitilis was investigated. In response to phosphate starvation,
      S. avermitilis PhoP, like Streptomyces coelicolor and Streptomyces lividans PhoP,
      activates the expression of phoRP, phoU, and pstS by binding to the PHO boxes in
      their promoter regions. Avermectin biosynthesis was significantly increased in
      DeltaphoP deletion mutants. Electrophoretic mobility gel shift assay (EMSA) and
      DNase I footprinting assays showed that PhoP can bind to a PHO box formed by two
      direct repeat units of 11 nucleotides located downstream of the transcriptional
      start site of aveR. By negatively regulating the transcription of aveR, PhoP
      directly affects avermectin biosynthesis in S. avermitilis. PhoP indirectly
      affects melanogenesis on Casaminoacids Minimal Medium (MMC) lacking supplemental
      phosphate. Nitrogen metabolism and some key genes involved in morphological
      differentiation and antibiotic production in S. avermitilis are also under the
      control of PhoP. 

PMID- 26298702
TI  - Capsular polysaccharide production by Streptococcus pneumoniae serotype 1: from
      strain selection to fed-batch cultivation.
AB  - Streptococcus pneumoniae is a human pathogen largely transmitted by aerosols.
      Vaccines are the main strategy against this pathogen, and the capsular
      polysaccharide (PS) is its major antigen. S. pneumoniae serotype 1 is associated
      with large outbreaks and epidemics of invasive diseases. The aims of this work
      were to screen serotype 1 strains to identify the best PS1 producer, evaluate
      three peptones for PS1 production, investigate the effects of culture medium
      components using a design of experiments (DoE), a statistic tool for
      optimization, and propose a new medium/cultivation strategy. After flask
      cultivation of nine strains, two that produced high PS1 and biomass values were
      chosen for further evaluation in the bioreactor, and ST595/01 was chosen as the
      best PS1 producer strain. Among the peptones tested (Casamino acids, Soytone, and
      Phytone), the highest PS1 production (298 mg/L) was reached with Phytone. Next,
      DoE (2(4-1)) was performed to evaluate the effects of yeast extract (YE),
      Phytone, L-asparagine (Asn), and L-glutamine (Gln), yielding the following
      results: Phytone presented positive effects (p < 0.05) for maximum production of
      biomass, PS1, acetate, and lactate; YE showed positive effects for biomass and
      acid production (p < 0.05); Gln exerted a minor positive effect on PS1 yield
      factor on glucose (p < 0.1); and Asn presented only an effect on acetate
      production (p < 0.1). Hence, a new culture medium was formulated based on
      Phytone, YE, and glucose, and batch and fed-batch cultivations were evaluated.
      The fed-batch cultivation showed almost 2 times the biomass and 2.5 times the PS1
      production as the batch culture, and 8-10 times higher PS1 production than has
      been previously reported. 

PMID- 26298703
TI  - Delusion and bi-ocular vision.
AB  - The delusional experience is the result of a grave disjunction in the psyche
      whose outcome is not readily predictable. Examination of the specific mode of
      disjunction may help us understand the nature and radical character of delusion.
      I will present the therapy of a psychotic patient who after many years of
      analysis and progresses in his life continues to show delusional episodes
      although limited and contained. In his case, the two visions, one delusional and
      the other real, remain distinct and differentiated from each other because they
      both possess the same perceptual character, that of reality. He has a bi-ocular
      vision of reality and not a binocular one because his vision lacks integration,
      as would necessarily be the case if the two visions could be compared with each
      other. The principle of non-contradiction ceases to apply in delusion. A
      corollary of the failure of the principle of non-contradiction is that, if a
      statement and its negation are both true, then any statement is true. Logicians
      call this consequence the principle of explosion. For this reason, the
      distinction between truth, reality, improbability, probability, possibility and
      impossibility is lost in the delusional system, thus triggering an omnipotent,
      explosive mechanism with a potentially infinite progression. The paper presents
      some thoughts for a possible analytic transformation of the delusional
      experience. 

PMID- 26298704
TI  - Survey of otorhinolaryngologists on their clinical examinations performed in
      patients with suspected sleep-disordered breathing.
AB  - There is currently no standardized ear, nose, and throat (ENT) clinical
      examination for patients with sleep-disordered breathing (SDB). As a result,
      there are large inter-individual differences in the examinations due to an
      inadequate estimation of the relevance of certain anatomic sites. We aimed to
      identify which examinations/dynamic tests are considered most relevant by German
      ENT physicians. A questionnaire was designed, evaluating 23 anatomic
      sites/dynamic tests of the upper aero-digestive tract. The questionnaire was sent
      to all German ENT departments (n = 153), including universities and other
      tertiary or secondary referral centers, by postal mail. In addition, almost all
      private ENT specialists registered with the German professional association (n =
      2496) were contacted via e-mail. Participants assessed how often they examined
      the sites/dynamic tests, subjective importance, and the impact on the therapeutic
      procedure. A mean score of relevance (mSOR) was generated (minimum score 1;
      maximum score 75) from these three items. The response rate for hospitals was
      58.8 %; while, it was 4.1 % for ENT specialists in private practice. Therefore,
      the total response rate was 7.3 %. Of the 23 assessed items, some showed a high
      overall relevance, such as the tonsils (mSOR 64.75), webbing (mSOR 58.14), uvula
      (mSOR 55.12), or tongue base (mSOR 53.99). Other examinations, such as simulated
      snoring (mSOR 19.34) or the Mueller maneuver (mSOR 18.98), were estimated as less
      relevant. Our data reflect the assessment of German otorhinolaryngologists on the
      clinical examination of SDB patients. The results should be considered as a basis
      for compiling a standardized procedure.

PMID- 26298705
TI  - Ecotoxicological effect of zinc pyrithione in the freshwater fish Gambusia
      holbrooki.
AB  - Currently diverse biocidal agents can be used for distinct applications, such as
      personal hygiene, disinfection, antiparasitic activity, and antifouling effects.
      Zinc pyrithione is an organometallic biocide, with bactericidal, algicidal and
      fungicidal activities. It has been recently incorporated in antifouling formulas,
      such as paints, which prevent the establishment of a biofilm on surfaces exposed
      to the aquatic environment. It has also been used in cosmetics, such as anti
      dandruff shampoos and soaps. Previously reported data has shown the presence of
      this substance in the aquatic compartment, a factor contributing to the potential
      exertion of toxic effects, and there is also evidence that photodegradation
      products of zinc pyrithione were involved in neurotoxic effects, namely by
      inhibiting cholinesterases in fish species. Additional evidence points to the
      involvement of zinc pyrithione in alterations of metal homeostasis and oxidative
      stress, in both aquatic organisms and human cell models. The present work
      assesses the potential ecotoxicity elicited by zinc pyrithione in the freshwater
      fish Gambusia holbrooki after an acute (96 h) exposure. The oxidative stress was
      assessed by the quantification of the activities of specific enzymes from the
      antioxidant defense system, such as catalase, and glutathione-S-transferases; and
      the extent of peroxidative damage was quantified by measuring the thiobarbituric
      acid reactive substances levels. Neurotoxicity was assessed through measurement
      of acetylcholinesterase activity; and a standardized method for the description
      and assessment of histological changes in liver and gills of was also used. Zinc
      pyrithione caused non-specific and reversible tissue alterations, both in liver
      and gills of exposed organisms. However, histopathological indices were not
      significantly different from the control group. In terms of oxidative stress
      biomarkers, none of the tested biomarkers indicated the occurrence of pro
      oxidative effects, suggesting that the oxidative pathway is not the major
      toxicological outcome of exposure to zinc pyrithione.

PMID- 26298706
TI  - Acetabular cartilage defects cause altered hip and knee joint coordination
      variability during gait.
AB  - BACKGROUND: Patients with acetabular cartilage defects reported increased pain
      and disability compared to those without acetabular cartilage defects. The
      specific effects of acetabular cartilage defects on lower extremity coordination
      patterns are unclear. The purpose of this study was to determine hip and knee
      joint coordination variability during gait in those with and without acetabular
      cartilage defects. METHODS: A combined approach, consisting of a semi
      quantitative MRI-based quantification method and vector coding, was used to
      assess hip and knee joint coordination variability during gait in those with and
      without acetabular cartilage lesions. FINDINGS: The coordination variability of
      the hip flexion-extension/knee rotation, hip abduction-adduction/knee rotation,
      and hip rotation/knee rotation joint couplings were reduced in the acetabular
      lesion group compared to the control group during loading response of the gait
      cycle. The lesion group demonstrated increased variability in the hip flexion
      extension/knee rotation and hip abduction-adduction/knee rotation joint
      couplings, compared to the control group, during the terminal stance/pre-swing
      phase of gait. INTERPRETATION: Reduced variability during loading response in the
      lesion group may suggest reduced movement strategies and a possible compensation
      mechanism for lower extremity instability during this phase of the gait cycle.
      During terminal stance/pre-swing, a larger variability in the lesion group may
      suggest increased movement strategies and represent a compensation or pain
      avoidance mechanism caused by the load applied to the hip joint.

PMID- 26298707
TI  - What Is New in Antibiotic Therapy in Community-Acquired Pneumonia? An Evidence
      Based Approach Focusing on Combined Therapy.
AB  - Despite all published literature, controversies remain about the optimal
      antibiotic treatment in community-acquired pneumonia. The most debated issue is
      whether it is necessary to empirically start one or two antibiotics, i.e. whether
      or not to cover atypical agents. A review of the literature published from 2005
      to present was completed, searching for new insights in antibiotic treatment in
      community-acquired pneumonia (CAP) focusing on monotherapy versus combined
      therapy. Forty-one articles were identified enrolling outpatients, and patients
      admitted to the ward and to the intensive care unit: 11 were meta-analyses, 8
      clinical trials and 22 observational-prospective and retrospective-studies.
      Although controversies remain in the treatment of CAP, the use of combination
      therapy seems to be associated with a lower mortality in case of severe CAP that
      requires intensive care unit (ICU) admission, especially when a beta-lactam
      macrolide association is delivered. Moreover, combination therapy is associated
      with better outcomes-although not always with a lower mortality-in cases of non
      ICU patients with risk factors for a poor outcome, bacteraemic pneumococcal
      pneumonia and high suspicion of infection by atypical agents. In this setting, it
      appears that the best choice of treatment may be a beta-lactam-macrolide regimen.

PMID- 26298708
TI  - Bioconcentration, biotransformation and elimination of pyrene in the arctic
      crustacean Gammarus setosus (Amphipoda) at two temperatures.
AB  - The influence of temperature on the bioaccumulation, toxicokinetics,
      biotransformation and depuration of pyrene was studied in the arctic marine
      amphipod Gammarus setosus. A two-compartment model was used to fit experimental
      values of total body burden, total metabolites and parent pyrene concentrations
      and to calculate toxicokinetic variables derived for two experimental treatments
      (2 and 8  degrees C). No statistically significant differences were observed with
      temperature for these toxicokinetic variables or bioconcentration factors.
      Contrarily, the Q10 values suggested that the toxicokinetic variables ke and km
      were temperature-dependent. This may be explained by the high standard deviation
      of the Q10 values. Q10 is the variation in the rate of a metabolic reaction with
      a 10  degrees C increase in temperature. Depuration rate constants were
      calculated from linear best fit equations applied to measured pyrene
      concentrations over time during the depuration phase of the experiment. During
      depuration, the parent pyrene was eliminated in two stages with faster
      elimination observed at 8  degrees C compared to 2  degrees C. This finding was
      also indicated by the Q10. No changes in total body burdens of metabolite
      concentrations were observed during the monitoring of depuration over a period of
      96 h. The biotransformation pathway of pyrene in G. setosus was also investigated
      in this study with two main phase II biotransformation products discovered by
      liquid chromatography. These products are conditionally identified as the
      sulphate and glucose conjugates of 1-hydroxy-pyrene. Overall, the study
      contributes new knowledge to the understanding of the fate of PAHs in arctic
      biota. In particular, the study provides valuable insight into the
      bioaccumulation and biotransformation of an important PAH and its metabolites in
      a species that serves as both a predator and prey in the arctic ecosystem. 

PMID- 26298709
TI  - Growth Inhibition Accompanied by MOB1 Upregulation in Human Acute Lymphoid
      Leukemia Cells by 3-Deazaneplanocin A.
AB  - Our purpose was to investigate the effect of 3-deazaneplanocin A (DZNep) on human
      T-cell acute lymphoid leukemia (T-ALL) cells, and to explore the underlying
      molecular mechanisms. The human T-ALL cell line Molt4 was treated with DZNep, and
      cell proliferation was examined. The expression of Mps one binder kinase
      activator 1 gene (MOB1) mRNA and protein was determined by RT-PCR and Western
      blotting, respectively. The histone modification effect of DZNep on the lysine 9
      of histone 3 associated with MOB1 promoters was examined with chromatin
      immunoprecipitation and quantitative PCR, and CpG methylation in MOB1 promoters
      was detected by bisulfite sequencing PCR. DZNep treatment inhibited the growth of
      Molt4 cells. The expressions of MOB1 genes were upregulated by DZNep treatment,
      and histone methylations in their promoters were significantly reduced. The
      results indicate that DZNep is a promising therapeutic compound for the treatment
      of human T-ALL. 

PMID- 26298710
TI  - The effect of variable arterial transducer level on the accuracy of pulse contour
      waveform-derived measurements in critically ill patients.
AB  - We know that a 10 cm departure from the reference level of pressure transducer
      position is equal to a 7.5 mmHg change of invasive hemodynamic pressure
      monitoring in a fluid-filled system. However, the relationship between the site
      level of a variable arterial pressure transducer and the pulse contour-derived
      parameters has yet to be established in critically ill patients. Moreover, the
      related quantitative analysis has never been investigated. Forty-two critically
      ill patients requiring PiCCO-Plus cardiac output monitoring were prospectively
      studied. The phlebostatic axis was defined as the zero reference level; the
      arterial pressure transducer was then vertically adjusted to different positions
      (+5, +10, +15, +20, -20, -15, -10, -5 cm) of departure from the zero reference
      site. The pulse contour waveform-derived parameters were recorded at each
      position. Elevation of the pressure transducer caused significantly positive
      changes in the continuous cardiac index (+CCI), stroke volume index (+SVI), and
      stroke volume variation (+SVV), and negative changes in the rate of left
      ventricular pressure rise during systole (-dP/dtmax), the systemic vascular
      resistance index (-SVRI), and vice versa. At the 5 cm position, the SVRI changes
      reached statistical significance with error. At the 10 cm position, the changes
      in CCI and dP/dtmax reached statistical significance with error, while the change
      in SVV reached statistical significance at 15 cm. The change rate of CCI was more
      than 5 % at the 15 cm position and approximately 10 % at the 20 cm position. On
      average, for every centimeter change of the transducer, there was a corresponding
      0.014 L/min/m(2) CCI change and 0.36 % change rate, a 1.41 mmHg/s dP/dtmax change
      and 0.13 % change rate, and a 25 dyne/s/cm(5) SVRI change and 1.2 % change rate.
      The variation of arterial transducer position can result in inaccurate
      measurement of pulse contour waveform-derived parameters, especially when the
      transducer's vertical distance is more than 10 cm from the phlebostatic axis.
      These findings have clinical implications for continuous hemodynamic monitoring. 

PMID- 26298711
TI  - Tibial slope correction combined with second revision ACL produces good knee
      stability and prevents graft rupture.
AB  - PURPOSE: Revision ACL reconstruction requires careful analysis of failure causes
      particularly in cases of two previous graft ruptures. Intrinsic factors as
      excessive tibial slope or narrow femoral notch increase failure risks but are
      rarely addressed in revision surgery. The authors report outcomes, at minimum
      follow-up of 2 years, for second revision ACL reconstructions combined with
      tibial deflexion osteotomy for correction of excessive slope (>12 degrees ).
      METHODS: Nine patients that underwent second revision ACL reconstruction combined
      with tibial deflexion osteotomy were retrospectively studied. The mean age was
      30.3 +/- 4.4 years (median 28; range 26-37), and mean follow-up was 4.0 +/- 2.0
      years (median 3.6; range 2.0-7.6). Autografts were harvested from the quadriceps
      tendon (n = 8) or hamstrings (n = 1), and tibial osteotomy was done by anterior
      closing wedge, without detachment of the patellar tendon, to obtain a slope of 3
      degrees  to 5 degrees . RESULTS: All patients had fused osteotomies, stable
      knees, and there were no intraoperative or postoperative complications. The mean
      posterior tibial slope decreased from 13.2 degrees  +/- 2.6 degrees  (median 13
      degrees ; range 12 degrees -18 degrees ) preoperatively to 4.4 degrees  +/- 2.3
      degrees  (median 4 degrees ; range 2 degrees -8 degrees ) postoperatively. The
      mean Lysholm score was 73.8 +/- 5.8 (median 74; range 65-82), and the IKDC-SKF
      was 71.6 +/- 6.1 (median 72.8; range 62.2-78.5). CONCLUSION: The satisfactory
      results of second revision ACL reconstruction combined with tibial deflexion
      osteotomy at minimum follow-up of 2 years suggest that tibia slope correction
      protects reconstructed ACL from fatigue failure in this study. The authors stress
      the importance of careful analysis failure causes prior to revision ACL
      reconstruction, and recommend correction of tibial slope if it exceeds 12 degrees
      , to reduce the risks of graft retear. LEVEL OF EVIDENCE: III.

PMID- 26298712
TI  - Midterm follow-up after implantation of a polyurethane meniscal scaffold for
      segmental medial meniscus loss: maintenance of good clinical and MRI outcome.
AB  - PURPOSE: The preservation of meniscal structure and function after segmental
      meniscal loss is of crucial importance to prevent early development of
      osteoarthritis. Implantation of artificial meniscal implants has been reported as
      a feasible treatment option. The purpose of this study was to assess the clinical
      and magnetic resonance imaging (MRI) results 4 years after implantation of a
      polyurethane scaffold for chronic segmental medial meniscus deficiency following
      partial medial meniscectomy. METHODS: Eighteen patients received arthroscopic
      implantation of an Actifit((r)) polyurethane meniscal implant (Orteq Sports
      Medicine, London, UK) for deficiency of the medial meniscus. Patients were
      followed at 6, 12, 24, and 48 months. Clinical outcome was assessed using
      established patient-reported outcome scores (KOOS, KSS, UCLA Activity Scale, VAS
      for pain). Radiological outcome was quantified by MRI scans after 6, 12, 24, and
      48 months evaluating scaffold morphology, tissue integration, and status of the
      articular cartilage as well as signs of inflammation. RESULTS: Median patient age
      was 32.5 years (range 17-49 years) with a median meniscal defect size of 44.5 mm
      (range 35-62 mm). Continuing improvement of the VAS and KSS Knee and Function
      Scores could be observed after 48 months compared to baseline, whereas
      improvement of the activity level according to UCLA continued only up to 24
      months and decreased from there on. The KOOS Score showed significant improvement
      in all dimensions. MRI scans showed reappearance of bone bruises in two patients
      with scaffold extrusion. No significant changes in the articular cartilage could
      be perceived. CONCLUSION: Arthroscopic treatment for patients with chronic
      segmental meniscal loss using a polyurethane meniscal implant can achieve
      sustainable midterm results regarding pain reduction and knee function. LEVEL OF
      EVIDENCE: IV.

PMID- 26298713
TI  - Effects of fatigue on lower limb, pelvis and trunk kinematics and lower limb
      muscle activity during single-leg landing after anterior cruciate ligament
      reconstruction.
AB  - PURPOSE: Because there are no studies that have evaluated the effects of fatigue
      on the kinematics of the trunk and pelvis or on muscle activation in subjects
      with ACL reconstruction, the aim of this study was to evaluate the effects of
      fatigue on the lower limb, pelvis and trunk kinematics and lower limb muscle
      activation in subjects with ACL reconstruction during a single-leg landing
      compared to a healthy control group. METHODS: The participants included 20
      subjects with ACL reconstruction (ACL reconstruction group-ACLRG) and 20 healthy
      subjects (control group-CG) who were aged between 18 and 35 years. Kinematic and
      electromyographic analyses were performed during a single-leg landing before and
      after fatigue. The fatigue protocol included a series of 10 squats, two vertical
      jumps, and 20 steps. RESULTS: The effects of fatigue were increased peak trunk
      flexion and increased activation of the vastus lateralis, biceps femoris (BF) and
      gluteus maximus (GMax) during the landing phase. CONCLUSION: After the fatigue
      protocol, an increase in peak trunk flexion and activation of the GMax and BF
      were observed, most likely as a strategy to reduce the load on the ACL. ACL
      injury prevention programs should include strength and endurance exercises for
      the hip and trunk extensor muscles so that they can efficiently control trunk
      flexion during landing. LEVEL OF EVIDENCE: Prospective comparative study, Level
      II.

PMID- 26298714
TI  - Stem cells in degenerative orthopaedic pathologies: effects of aging on
      therapeutic potential.
AB  - PURPOSE: The purpose of this study was to summarize the current evidence on the
      use of stem cells in the elderly population with degenerative orthopaedic
      pathologies and to highlight the pathophysiologic mechanisms behind today's
      therapeutic challenges in stem cell-based regeneration of destructed tissues in
      the elderly patients with osteoarthritis (OA), degenerative disc disease (DDD),
      and tendinopathies. METHODS: Clinical and basic science studies that report the
      use of stem cells in the elderly patients with OA, DDD, and tendinopathies were
      identified using a PubMed search. The studies published in English have been
      assessed, and the best and most recent evidence was included in the current
      study. RESULTS: Evidence suggests that, although short-term results regarding the
      effects of stem cell therapy in degenerative orthopaedic pathologies can be
      promising, stem cell therapies do not appear to reverse age-related tissue
      degeneration. Causes of suboptimal outcomes can be attributed to the decrease in
      the therapeutic potential of aged stem cell populations and the regenerative
      capacity of these cells, which might be negatively influenced in an aged
      microenvironment within the degenerated tissues of elderly patients with OA, DDD,
      and tendinopathies. CONCLUSIONS: Clinical protocols guiding the use of stem cells
      in the elderly patient population are still under development, and high-level
      randomized controlled trials with long-term outcomes are lacking. Understanding
      the consequences of age-related changes in stem cell function and responsiveness
      of the in vivo microenvironment to stem cells is critical when designing cell
      based therapies for elderly patients with degenerative orthopaedic pathologies.

PMID- 26298716
TI  - Risk and Risk Periods for Stroke and Acute Myocardial Infarction in Patients with
      Central Retinal Artery Occlusion.
AB  - PURPOSE: To investigate the risk of stroke and acute myocardial infarction (AMI)
      in patients with incident central retinal artery occlusion (CRAO). DESIGN: A self
      controlled case series (SCCS) study. PARTICIPANTS: Patients with incident CRAO
      from the entire Korean population of 48 million individuals. METHODS: We used the
      Korean national claim database (2007-2011) for analyses. After identifying
      patients with incident CRAO, the relative incidence rate ratios (IRRs) for stroke
      and AMI in risk periods were measured in these patients using a SCCS method. MAIN
      OUTCOME MEASURES: The IRRs of stroke and AMI by risk periods. RESULTS: Of 1655
      patients with incident CRAO in 2009-2010, 165 had stroke/AMI (ischemic stroke in
      139, hemorrhagic stroke in 13, and AMI in 15) in the observation period spanning
      365 days before and after the occurrence of CRAO. The IRR of stroke/AMI 1 to 30
      days after CRAO occurrence significantly increased (14.0; 95% confidence interval
      [CI], 8.90-22.00); the IRR peaked during the 1 to 7 days after CRAO occurrence
      (44.51; 95% CI, 27.07-73.20), and the increased risk was present for the first 30
      days. The IRR of stroke/AMI also significantly increased 1 to 30 days (6.82; 95%
      CI, 4.01-11.60) and 31 to 90 days (2.86; 95% CI, 1.66-4.93) before CRAO
      occurrence. Subanalysis for only ischemic stroke showed similar, magnified IRRs
      in the risk periods compared with all events. The IRRs were not significantly
      different between sexes or age groups (<65 vs. >=65 years). CONCLUSIONS: Patients
      with incident CRAO are at increased risk of ischemic stroke just after CRAO
      occurrence, and the risk is particularly increased during the first week
      immediately after the CRAO occurrence. The results suggest that patients with
      incident CRAO require immediate neurologic evaluation and preventive treatment to
      reduce mortality and morbidity.

PMID- 26298717
TI  - The Onion Sign in Neovascular Age-Related Macular Degeneration Represents
      Cholesterol Crystals.
AB  - PURPOSE: To investigate the frequency, natural evolution, and histologic
      correlates of layered, hyperreflective, subretinal pigment epithelium (sub-RPE)
      lines, known as the onion sign, in neovascular age-related macular degeneration
      (AMD). DESIGN: Retrospective observational cohort study and experimental
      laboratory study. PARTICIPANTS: Two hundred thirty eyes of 150 consecutive
      patients with neovascular AMD and 40 human donor eyes with histopathologic
      diagnosis of neovascular AMD. METHODS: Spectral-domain optical coherence
      tomography (SD OCT), near-infrared reflectance (NIR), color fundus images, and
      medical charts were reviewed. Donor eyes underwent multimodal ex vivo imaging,
      including SD OCT, before processing for high-resolution histologic analysis. MAIN
      OUTCOME MEASURES: Presence of layered, hyperreflective sub-RPE lines, qualitative
      analysis of their change in appearance over time with SD OCT, histologic
      correlates of these lines, and associated findings within surrounding tissues.
      RESULTS: Sixteen of 230 eyes of patients (7.0%) and 2 of 40 donor eyes (5.0%)
      with neovascular AMD had layered, hyperreflective sub-RPE lines on SD OCT
      imaging. These appeared as refractile, yellow-gray exudates on color imaging and
      as hyperreflective lesions on NIR. In all 16 patient eyes, the onion sign
      persisted in follow-up for up to 5 years, with fluctuations in the abundance of
      lines and association with intraretinal hyperreflective foci. Patients with the
      onion sign disproportionately were taking cholesterol-lowering medications
      (P=0.025). Histologic analysis of 2 donor eyes revealed that the hyperreflective
      lines correlated with clefts created by extraction of cholesterol crystals during
      tissue processing. The fluid surrounding the crystals contained lipid, yet was
      distinct from oily drusen. Intraretinal hyperreflective foci correlated with
      intraretinal RPE and lipid-filled cells of probable monocytic origin.
      CONCLUSIONS: Persistent and dynamic, the onion sign represents sub-RPE
      cholesterol crystal precipitation in an aqueous environment. The frequency of the
      onion sign in neovascular AMD in a referral practice and a pathology archive is
      5% to 7%. Associations include use of cholesterol-lowering medication and
      intraretinal hyperreflective foci attributable to RPE cells and lipid-filled
      cells of monocyte origin.

PMID- 26298719
TI  - Lamina Cribrosa Reversal after Trabeculectomy and the Rate of Progressive Retinal
      Nerve Fiber Layer Thinning.
AB  - PURPOSE: To determine whether the reversal of lamina cribrosa (LC) displacement
      observed after trabeculectomy is associated with the rate of progressive retinal
      nerve fiber layer (RNFL) thinning in primary open-angle glaucoma (POAG). DESIGN:
      Observational case series. PARTICIPANTS: Thirty-four patients with POAG who
      underwent trabeculectomy and were followed up for at least 2.5 years, during
      which the RNFL thickness was measured by serial spectral-domain (SD) optical
      coherence tomography (OCT). METHODS: The participants underwent enhanced depth
      imaging scanning of the optic nerve using SD OCT before surgery (PREOP), at a 6
      month postoperative follow-up (FU1), and at a subsequent follow-up that was
      performed at least 2.5 years postoperatively (FU2), and serial RNFL thickness was
      measured at least 5 times during the study period. Preoperative and postoperative
      LC depths (LCDs) as determined on 7 selected B-scan images from each eye were
      averaged to produce the mean LCD. The rate of RNFL thinning was determined by
      linear regression of serial OCT RNFL thickness measurements over time. MAIN
      OUTCOME MEASURES: Factors associated with the rate of OCT RNFL thinning. RESULTS:
      The intraocular pressure (IOP) decreased from 23.8+/-7.9 mmHg (mean+/-standard
      deviation) to 11.0+/-4.4 mmHg at FU1 (P<0.001) and subsequently increased to
      13.1+/-5.2 mmHg at an overall follow-up of 3.5+/-0.8 years (P=0.003). The LCD was
      reduced from 589.90+/-148.32 to 508.57+/-136.28 MUm at FU1 (P<0.001). A
      subsequent slight but nonsignificant increase in the LCD was noted at FU2
      (516.48+/-145.87 MUm; P=0.410). A faster rate of RNFL thinning was associated
      with a shorter follow-up period (P=0.032), higher IOP at PREOP (P=0.011) and FU2
      (P=0.014), and a larger increase in LCD from FU1 to FU2 (P<0.001). The changes in
      LCD between PREOP and FU1 and between PREOP and FU2 were not associated with the
      rate of RNFL thinning. CONCLUSIONS: Eyes with sustained LCD reduction over a long
      period had a slow rate of progressive RNFL thinning after trabeculectomy. A large
      LCD reduction in the early postoperative period was not associated with the long
      term rate of progression if it was not maintained during subsequent follow-up.

PMID- 26298720
TI  - [Single-port video-assisted thoracic surgery in an awake patient].
AB  - Video-assisted thoracic surgery is traditionally carried out with general
      anaesthesia and endotracheal intubation with double lumen tube. However, in the
      last few years procedures, such as lobectomies, are being performed with loco
      regional anaesthesia, with and without sedation, maintaining the patient awake
      and with spontaneous breathing, in order to avoid the inherent risks of general
      anaesthesia, double lumen tube intubation and mechanical ventilation. This
      surgical approach has also shown to be effective in that it allows a good level
      of analgesia, maintaining a correct oxygenation and providing a better post
      operative recovery. Two case reports are presented in which video-assisted
      thoracic surgery was used, a lung biopsy and a lung resection, both with epidural
      anaesthesia and maintaining the patient awake and with spontaneous ventilation,
      as part of a preliminary evaluation of the anaesthetic technique in this type of
      surgery. 

PMID- 26298721
TI  - Oxidative stress induced by low-dose doxorubicin promotes the invasiveness of
      osteosarcoma cell line U2OS in vitro.
AB  - Reactive oxygen species (ROS) are known to mediate doxorubicin (DOX)-induced
      apoptosis and are the major cause of DOX toxicity. We introduce a novel in vitro
      phenomenon of osteosarcoma (OS) cell line caused by low-dose DOX-induced
      oxidative stress. Human osteosarcoma cell line U2OS was used for the experiments.
      Hydrogen peroxide (H2O2) and the antioxidant compound N-acetylcysteine (NAC) were
      used to investigate the involvement of oxidative stress. In proliferation assays,
      low dose of DOX (below 200 nM) did not affect U2OS proliferation significantly
      for up to 48 h. In Matrigel(TM) invasion assay, DOX increased the invasiveness of
      U2OS at around 100 nM, which is a subclinical concentration. Quantitative real
      time polymerase chain reaction and gelatin zymography showed increased MMP-9
      expression and increased MMP-9 enzymatic activity, respectively, in the presence
      of DOX doses that increased the invasiveness of U2OS. H2O2, a representative
      source of ROS, also increased the invasiveness of U2OS as DOX did, with similar
      patterns. However, when the cells were pre-treated with NAC, no DOX- or H2O2
      mediated increase of invasiveness or MMP-9 expression was evident. The results
      suggest that oxidative stress induced by low-dose DOX promotes the invasiveness
      of osteosarcoma cell line U2OS in vitro, through MMP-9 induction. 

PMID- 26298723
TI  - miR-132 upregulation promotes gastric cancer cell growth through suppression of
      FoxO1 translation.
AB  - Gastric carcinoma (GC) is a prevalent malignant cancer worldwide and is highly
      lethal due to its fast growth. Hence, treatments to suppress GC cell growth may
      be applied together with surgery and chemotherapy to increase therapeutic
      outcome. Previous studies have shown the involvement of some microRNAs (miRNAs or
      miRs) in the carcinogenesis of GC, whereas a role of miR-132 in regulating the
      growth of GC has not been reported. Here, we report that overexpression of miR
      132 in GC cells decreased FoxO1 protein levels, whereas depletion of miR-132
      increased FoxO1 protein levels, without altering FoxO1 transcripts.
      Bioinformatics analyses showed that miR-132 bound to 3'-untranslated region (3'
      UTR) of FoxO1 messenger RNA (mRNA) to prevent its translation, which was
      confirmed by luciferase reporter assay. Moreover, miR-132-mediated suppression of
      FoxO1 in GC cells resulted in a significant increase in GC cell growth in vitro
      and in vivo, while increases in FoxO1 by expression of antisense of miR-132
      significantly decreased GC cell growth in vitro and in vivo. Finally, miR-132
      levels were found significantly increased in GC specimens, compared to those in
      paired non-tumor gastric tissue. Together, our data suggest that miR-132
      upregulation in GC cells may promote cell growth through suppression of FoxO1
      translation.

PMID- 26298722
TI  - MiR-944 functions as a novel oncogene and regulates the chemoresistance in breast
      cancer.
AB  - MircroRNAs are emerging as critical regulators in carcinogenesis and
      chemoresistance in multiple cancer types. In this study, we observed that the miR
      944 level was upregulated in breast cancer patients' serum and tumor tissues,
      suggesting that miR-944 is a tumor promoter in breast cancer. To investigate the
      role of miR-944, we performed gain- and loss-of-function experiments in vitro. We
      then demonstrated that miR-944 promotes cell proliferation and tumor metastasis
      in breast cancer cell lines. Furthermore, we indicated that miR-944 is associated
      with cisplatin resistance by targeting BNIP3. Knockdown of the miR-944 by
      specific inhibitors significantly increased the cytotoxicity of cisplatin in
      cisplatin-resistant MCF-7 cells (MCF-7/R). Importantly, we found that the
      sensitization of miR-944 inhibitors to cisplatin cytotoxicity was abolished by
      BNIP3 siRNA which decreased the expression of BNIP3 gene. Finally, we
      demonstrated that miR-944 inhibitors promoted the loss of mitochondrial membrane
      potential (MMP) caused by cisplatin in MCF-7/R cells, resulting in the release of
      mitochondria-derived apoptogenic proteins into cytoplasm, and then, the caspase-3
      was activated. In summary, our study showed that miR-944 functions as a novel
      oncogene and regulates the cisplatin resistance in breast cancer. The miR-944
      BNIP3-MMP-caspase-3 pathway might be a novel target for the chemotherapy of
      breast cancer. 

PMID- 26298724
TI  - MicroRNA-148a inhibits migration of breast cancer cells by targeting MMP-13.
AB  - Breast cancer is a threat to the health of women, and metastasis of breast cancer
      cells plays an important role in the deterioration of breast cancer. MicroRNAs
      play a critical role in the tumorigenesis and development of breast cancer.
      MicroRNA-148a (miR-148a) is associated with the growth and metastasis of tumor
      cells. In the present study, we investigated the role of miR-148a in migration of
      breast cancer cells as well as the underlying mechanism. MiR-148a was found to
      inhibit the proliferation and migration of breast cancer cells. To further
      explore the mechanism through which miR-148a plays its antitumor role, matrix
      metalloproteinase-13 (MMP-13) was identified as a target of miR-148a by western
      blot and luciferase reporter assay. Moreover, silence of MMP-13 mimicked the
      effect of miR-148a, whereas overexpression of MMP-13 rescued the impaired
      migration caused by miR-148a. Our study demonstrates that miR-148a inhibits the
      migration of breast cancer cells by targeting MMP-13 and also lays theoretical
      foundation for further exploration for the function of miR-148a. 

PMID- 26298725
TI  - Overexpression of TRIP6 promotes tumor proliferation and reverses cell adhesion
      mediated drug resistance (CAM-DR) via regulating nuclear p27(Kip1) expression in
      non-Hodgkin's lymphoma.
AB  - Recent studies have identified that thyroid hormone receptor-interacting protein
      6 (TRIP6) is implicated in tumorigenesis. However, the functional role of TRIP6
      in non-Hodgkin's lymphoma (NHL) has never been elucidated. In this study, we
      demonstrated that TRIP6 is reversely correlated with the clinical outcomes of NHL
      patients. Western blot and immunohistochemical analysis revealed that TRIP6
      expression is lower in indolent lymphoma than in progressive lymphoma. Kaplan
      Meier survival curves indicated that the upregulation of TRIP6 is significantly
      associated with poor overall survival. Moreover, patients with higher expression
      of TRIP6 are prone to shorter time to recurrence. Furthermore, we also found that
      TRIP6 can promote the proliferation of NHL cells via regulating cell cycle
      progression. In addition, adhesion of lymphoma cells to fibronectin (FN)
      decreased TRIP6 expression, which led to the upregulation of nuclear p27(Kip1)
      expression by decreasing phosphorylation of p27(Kip1) at T157. Importantly,
      overexpression of TRIP6 can reverse cell adhesion-mediated drug resistance (CAM
      DR) phenotype in NHL. In summary, these results suggest that TRIP6 is a novel
      prognostic indicator for NHL patients and may shed new insights into the
      important role of TRIP6 in cancer development. 

PMID- 26298726
TI  - The study of MED12 gene mutations in uterine leiomyomas from Iranian patients.
AB  - Uterine leiomyomas are the most common gynecologic benign tumors of the female
      genital tract that cause a variety of health problems including, abnormal
      menstrual bleeding, pelvic pain, placenta displacement, premature labor, and
      miscarriages. Recently, studies showed that recurrent somatic mutations in MED12
      exon 2 are the major cause of uterine leiomyomas in different ethnic groups. In
      order to validate these results in Iranian population, we performed mutational
      analysis of exon 2 and the flanking intronic regions by using single-strand
      conformational polymorphism (SSCP) and sequencing analyses in a series of 103
      uterine leiomyomas samples. MED12 gene was mutated in 31.07 % of the uterine
      leiomyomas. Mutations were consisted of 20 missense (62.5 %) and 12 in-frame
      deletion (37.5 %) mutations and were not detected in normal myometrial tissue.
      Although this is the lowest mutation frequency reported so far, MED12 mutations
      are associated with fibroid pathogenesis in the studied population. Understanding
      the molecular mechanisms responsible for the pathogenesis of uterine leiomyoma
      will play an important role in designing new therapeutic strategies. 

PMID- 26298715
TI  - Benefits of Systemic Anti-inflammatory Therapy versus Fluocinolone Acetonide
      Intraocular Implant for Intermediate Uveitis, Posterior Uveitis, and Panuveitis:
      Fifty-four-Month Results of the Multicenter Uveitis Steroid Treatment (MUST)
      Trial and Follow-up Study.
AB  - PURPOSE: To compare the benefits of fluocinolone acetonide implant therapy versus
      systemic corticosteroid therapy supplemented (when indicated) with
      immunosuppression for intermediate uveitis, posterior uveitis, and panuveitis.
      DESIGN: Additional follow-up of a randomized comparative effectiveness trial
      cohort. PARTICIPANTS: Two hundred fifty-five patients with intermediate uveitis,
      posterior uveitis, or panuveitis randomized to implant or systemic therapy. MAIN
      OUTCOME MEASURES: Best-corrected visual acuity (BCVA), visual field mean
      deviation (MD), activity of uveitis, and presence of macular edema (per reading
      center grading) ascertained prospectively. METHODS: Trial participants were
      followed-up for 54 months from original randomization. RESULTS: The visual
      function trajectory in uveitic eyes demonstrated a similar (P = 0.73) degree of
      modest (not statistically significant) improvement from baseline to 54 months in
      both groups (mean improvement in BCVA at 54 months, 2.4 and 3.1 letters in the
      implant and systemic groups, respectively). Many had excellent initial visual
      acuity, limiting the potential for improvement. The mean automated perimetry MD
      score remained similar to baseline throughout 48 months of follow-up in both
      groups. Overall control of inflammation was superior in the implant group at
      every time point assessed (P < 0.016), although most eyes in the systemic therapy
      arm also showed substantial improvement, achieving complete control or low levels
      of inflammation. Although macular edema improved significantly more often with
      implant treatment within the first 6 months, the systemic group gradually
      improved over time such that the proportions with macular edema converged in the
      2 groups by 36 months and overlapped thereafter (P = 0.41 at 48 months).
      CONCLUSIONS: Visual outcomes of fluocinolone acetonide implant and systemic
      treatment for intermediate uveitis, posterior uveitis, and panuveitis were
      similarly favorable through 54 months. The implant maintained a clear advantage
      in controlling inflammation through 54 months. Nevertheless, with systemic
      therapy, most patients also experienced greatly improved inflammatory status.
      Macular edema improved equally with longer follow-up. Based on cost effectiveness
      and side-effect considerations, systemic therapy may be indicated as the initial
      treatment for many bilateral uveitis cases. However, implant therapy is a
      reasonable alternative, especially for unilateral cases and when systemic therapy
      is not feasible or is not successful.

PMID- 26298727
TI  - Ruxolitinib induces autophagy in chronic myeloid leukemia cells.
AB  - Ruxolitinib is the first agent used in myelofibrosis treatment with its potent
      JAK2 inhibitory effect. In this novel study, we aimed to discover the anti
      leukemic effect of ruxolitinib in K-562 human chronic myeloid leukemia cell line
      compared to NCI-BL 2171 human healthy B lymphocyte cell line. Cytotoxic effect of
      ruxolitinib was determined by using WST-1 assay. IC50 values for K-562 and NCI-BL
      2171 cell lines were defined as 20 and 23.6 MUM at the 48th hour, respectively.
      Autophagic effects of ruxolitinib were detected by measuring LC3B-II protein
      formation. Ruxolitinib induced autophagic cell death in K-562 and NCI-BL 2171
      cell lines 2.11- and 1.79-fold compared to control groups, respectively. To
      determine the autophagy-related gene expression changes, total RNA was isolated
      from K-562 and NCI-BL 2171 cells treated with ruxolitinib and untreated cells as
      control group. Reverse transcription procedure was performed for cDNA synthesis,
      and gene expressions were shown by RT-qPCR. Ruxolitinib treatment caused a
      notable decrease in expression of AKT, mTOR, and STAT autophagy inhibitor genes
      in K-562 cells, contrariwise control cell line. Ruxolitinib is a promising agent
      in chronic myeloid leukemia treatment by blocking JAK/STAT pathway known as
      downstream of BCR-ABL and triggering autophagy. This is the first study that
      reveals the relationship between ruxolitinib and autophagy induction. 

PMID- 26298718
TI  - Quality of Life and Risks Associated with Systemic Anti-inflammatory Therapy
      versus Fluocinolone Acetonide Intraocular Implant for Intermediate Uveitis,
      Posterior Uveitis, or Panuveitis: Fifty-four-Month Results of the Multicenter
      Uveitis Steroid Treatment Trial and Follow-up Study.
AB  - PURPOSE: To evaluate the risks and quality-of-life (QoL) outcomes of fluocinolone
      acetonide implant versus systemic therapy with corticosteroid and
      immunosuppression when indicated for intermediate uveitis, posterior uveitis, and
      panuveitis. DESIGN: Additional follow-up of a randomized trial cohort.
      PARTICIPANTS: Two hundred fifty-five patients with intermediate uveitis,
      posterior uveitis, or panuveitis, randomized to implant or systemic therapy.
      METHODS: Randomized subjects with intermediate uveitis, posterior uveitis, or
      panuveitis (479 eyes) were followed up over 54 months, with 79.2% completing the
      54-month visit. MAIN OUTCOME MEASURES: Local and systemic potential complications
      of the therapies and self-reported health utility and vision-related and generic
      health-related QoL were studied prospectively. RESULTS: Among initially phakic
      eyes, cataract and cataract surgery occurred significantly more often in the
      implant group (hazard ratio [HR], 3.0; P = 0.0001; and HR, 3.8; P < 0.0001,
      respectively). In the implant group, most cataract surgery occurred within the
      first 2 years. Intraocular pressure elevation measures occurred more frequently
      in the implant group (HR range, 3.7-5.6; all P < 0.0001), and glaucoma (assessed
      annually) also occurred more frequently (26.3% vs. 10.2% by 48 months; HR, 3.0; P
      = 0.0002). In contrast, potential complications of systemic therapy, including
      measures of hypertension, hyperlipidemia, diabetes, bone disease, and hematologic
      and serum chemistry indicators of immunosuppression toxicity, did not differ
      between groups through 54 months. Indices of QoL initially favored implant
      therapy by a modest margin. However, all summary measures of health utility and
      vision-related or generic health-related QoL were minimally and nonsignificantly
      different by 54 months, with the exception of the 36-item Short-Form Health
      Survey physical component summary score, which favored implant by a small margin
      at 54 months (3.17 on a scale of 100; P = 0.01, not adjusted for multiple
      comparisons). Mean QoL results were favorable in both groups. CONCLUSIONS: These
      results suggest that fluocinolone acetonide implant therapy is associated with a
      clinically important increased risk of glaucoma and cataract with respect to
      systemic therapy, suggesting that careful monitoring and early intervention to
      prevent glaucoma is warranted with implant therapy. Systemic therapy subjects
      avoided a significant excess of toxicities of systemic corticosteroid and
      immunosuppressive therapies in the trial. Self-reported QoL measures initially
      favored implant therapy, but over time the measures converged, with generally
      favorable QoL in both groups.

PMID- 26298730
TI  - Optimal timing of clopidogrel discontinuation in Japanese patients: platelet
      aggregation test using the VerifyNow(r) system.
AB  - OBJECTIVE: The Japanese Circulation Society recommends discontinuation of
      antiplatelet therapy 7-14 days before major surgery. However, reports on the
      relationship between the timing of clopidogrel discontinuation and the risk of
      postoperative bleeding in Japanese subjects are lacking. We assessed the optimal
      timing of clopidogrel discontinuation before elective surgery using the
      VerifyNow(r) P2Y12 assay. In addition, the relationship between preoperative
      platelet function and risk of postoperative bleeding was evaluated. METHODS:
      Study 1: Between June 2012 and December 2014, Platelet function was examined by
      the VerifyNow P2Y12 assay in patients scheduled for cardiac surgery, every other
      day after clopidogrel cessation. Study 2: We compared the preoperative platelet
      function, measured by the VerifyNow, with the postoperative bleeding. RESULTS:
      Study 1: Twenty-four patients were included in this study. The mean P2Y12
      reaction units (PRU) on Day-0 was 186, and increased significantly to 283 PRU on
      Day-7 in a time-dependent manner after clopidogrel discontinuation (p = 0.001).
      The mean PRU value significantly exceeded the cutoff of 230 on Day-5. Study 2:
      Correlation between the preoperative aspirin reaction units (ARU) and
      postoperative bleeding showed a slight inverse correlation in patients undergoing
      aortic valve replacement (rS = -0.363, p = 0.013), mitral valve plasty (rS = 
      0.300, p = 0.085) and off-pump coronary artery bypass (rS = -0.176, p = not
      significant). CONCLUSION: Platelet aggregation had already recovered at 5 days
      after clopidogrel cessation. Surgeons could consider decreasing the interval from
      clopidogrel discontinuation to surgery from the recommended 7-14 days. The
      VerifyNow assay can be used to predict the risk of perioperative bleeding.

PMID- 26298729
TI  - Diverse effects of Brilliant Blue G administration in models of trigeminal
      activation in the rat.
AB  - Activation of the trigeminal system plays an important role in the pathomechanism
      of headaches. A better understanding of trigeminal pain processing is expected to
      provide information helping to unravel the background of these diseases. ATP, a
      key modulator of nociceptive processing, acts on ligand-gated P2X receptors.
      Antagonists of the P2X7 receptors, such as Brilliant Blue G (BBG), have proved
      effective in several models of pain. We have investigated the effects of BBG
      after electrical stimulation of the trigeminal ganglion and in the orofacial
      formalin test in the rat. The right trigeminal ganglion of male rats was
      stimulated either with 5 Hz, 0.5 mA pulses for 5 min (mild procedure) or with 10
      Hz, 0.5 mA pulses for 30 min (robust procedure), preceded by 50 mg/kg i.v. BBG.
      The animals were processed for c-Fos and calcitonin gene-related peptide (CGRP)
      immunohistochemistry. In the orofacial formalin test, 50 MUL of 1.5 % formalin
      was injected into the right whisker pad of awake rats, following the pre
      treatment with BBG. Behaviour was monitored for 45 min, and c-Fos and CGRP
      immunohistochemistry was performed. BBG attenuated the increase in c-Fos-positive
      cells in the caudal trigeminal nucleus (TNC) after robust stimulation, but not
      after mild stimulation. No alterations in CGRP levels were found with either
      methodology. BBG did not mitigate either the behaviour or the increase in c-Fos
      positive cells in the TNC during the orofacial formalin test. These results
      indicate that P2X7 receptors may have a role in the modulation of nociception in
      the trigeminal system.

PMID- 26298731
TI  - Impact of surgery, radiation and systemic therapy on the outcomes of patients
      with dendritic cell and histiocytic sarcomas.
AB  - BACKGROUND: Neoplasms of histiocytic and dendritic cell origin, including
      follicular dendritic cell sarcoma (FDCS), histiocytic sarcoma (HS) and
      interdigitating dendritic cell sarcoma (IDCS), are extremely rare, and data on
      their natural history and treatment outcomes are sparse. We evaluated the impact
      of surgery, radiation and systemic therapies on overall survival (OS). METHODS:
      We conducted a retrospective chart review of patients with FDCS, IDCS and HS
      treated at Memorial Sloan Kettering Cancer Center between 1995 and 2014. RESULTS:
      We identified 31, 15 and 7 patients with FDCS, HS and IDCS, respectively. Median
      age was 48.7, 42.3 and 58.8years for FDCS, HS and IDCS, respectively. Only a
      slight disparity in gender distribution existed for FDCS and HS; however, IDCS
      predominantly affected males (6:1). The most common sites of presentation were
      abdomen and pelvis (42%), extremities (33%) and head and neck (57%) for FDCS, HS
      and IDCS, respectively. At diagnosis, 74%, 40% and 86% of patients presented with
      localised disease in FDCS, HS and IDCS, respectively. Patients with localised
      disease had significantly improved OS than those with metastatic disease in FDCS
      (P=0.04) and IDCS (P=0.014) but not in HS (P=0.95). In FDCS and HS, adjuvant or
      neo-adjuvant therapy was not associated with improved OS compared with
      observation. In IDCS, surgery alone provided a 5-year overall survival rate of
      71%. CONCLUSIONS: Adjuvant or neo-adjuvant treatment in FDCS and HS did not
      affect OS. Patients with IDCS had an excellent outcome with surgery. In the
      metastatic setting, chemotherapy and small molecule inhibitors may provide
      benefit.

PMID- 26298728
TI  - Parkinson's disease between internal medicine and neurology.
AB  - General medical problems and complications have a major impact on the quality of
      life in all stages of Parkinson's disease. To introduce an effective treatment, a
      comprehensive analysis of the various clinical symptoms must be undertaken. One
      must distinguish between (1) diseases which arise independently of Parkinson's
      disease, and (2) diseases which are a direct or indirect consequence of
      Parkinson's disease. Medical comorbidity may induce additional limitations to
      physical strength and coping strategies, and may thus restrict the efficacy of
      the physical therapy which is essential for treating hypokinetic-rigid symptoms.
      In selecting the appropriate medication for the treatment of any additional
      medical symptoms, which may arise, its limitations, contraindications and
      interactions with dopaminergic substances have to be taken into consideration.
      General medical symptoms and organ manifestations may also arise as a direct
      consequence of the autonomic dysfunction associated with Parkinson's disease. As
      the disease progresses, additional non-parkinsonian symptoms can be of concern.
      Furthermore, the side effects of Parkinson medications may necessitate the
      involvement of other medical specialists. In this review, we will discuss the
      various general medical aspects of Parkinson's disease. 

PMID- 26298733
TI  - Successful Hepatectomy Using Venovenous Bypass in a Patient With Carcinoid Heart
      Disease and Severe Tricuspid Regurgitation.

PMID- 26298732
TI  - Sudden hearing loss: National survey in Spain.
AB  - INTRODUCTION: The objective of our study was to identify the diagnostic and
      therapeutic approaches in the different ENT Departments of Spain with respect to
      sudden deafness. We wanted to establish a basis to help to create a new nation
      wide consensus, unifying treatment, diagnostic and follow-up criteria for this
      disease. METHODS: We carried out an anonymous Internet survey, addressing Spanish
      ENT doctors nation-wide (n=2,029), gathering in 33 questions different aspects
      about diagnostic criteria, additional tests, treatment procedures and prognostic
      factors in sudden deafness, according to the different protocols and experience
      of the participants in the survey. RESULTS: A total of 293 Spanish ENT doctors
      (14%) took part anonymously. In relation to diagnostic criteria, is the most
      noteworthy was the requisite of a confirmed neurosensorial loss (91.1%) followed
      by "initiated in less than three days" (75%) and 3 consecutive frequencies
      affected (76.4%). More than half of the participants requested an MRI of the
      IAC/CPA (68.7%) and 88.2% used gadolinium in this test. The prognostic factor
      most frequently considered was delay in commencement of treatment onset (84.8%).
      As far as treatment of primary cases, most of the responders agreed on the use of
      corticosteroids (99.7%). Oral administration was the most widely used (66%),
      followed by intravenous (29.6%) and intratympanic (1.4%) administration. Ninety
      two percent had not had any major complications with systemic steroids.
      Intratympanic treatments were used by 70% of responders for rescue in failure.
      CONCLUSIONS: In Spain there is currently a significant disparity of concepts
      regarding the diagnosis of sudden deafness, and more agreement as to using
      steroids as their treatment. This highlights the need to implement measures to
      promote a better approach, which would be homogeneous and consensual, to this
      condition.

PMID- 26298734
TI  - Response to Proposed Mechanism for "Air" in the Aorta.

PMID- 26298735
TI  - Acquired Coronary Cameral Fistula Following Aortic Valve Replacement.

PMID- 26298736
TI  - CASE 11--2015: Intraoperative Transthoracic Cardiac and Pulmonary
      Ultrasonography.

PMID- 26298738
TI  - Irisin, a novel myokine is an independent predictor for sarcopenia and carotid
      atherosclerosis in dialysis patients.
AB  - OBJECTIVE: In end-stage renal disease, deleterious effect of sarcopenia on
      cardiovascular disease has been explained mainly by chronic inflammation.
      However, evidence emerged that skeletal muscles mediate their protective effect
      against sarcopenia by secreting myokines. Therefore, we sought to investigate the
      effect of irisin, a recently introduced myokine, on the association between
      sarcopenia and cardiovascular disease in peritoneal dialysis (PD) patients.
      METHODS: Serum irisin concentrations were assessed by enzyme-linked immunosorbent
      assay in 102 prevalent PD patients and 35 age- and sex-matched controls. To
      determine sarcopenia and cardiovascular disease, anthropometric indices including
      mid-arm muscle circumference (MAMC) and carotid intima-media thickness (cIMT)
      were measured. RESULTS: Serum irisin concentrations were significantly lower in
      PD patients than in controls (184.2 +/- 88.0 vs. 457.2 +/- 105.5 ng/mL, P <
      0.001). In PD patients, univariate linear regression analysis showed that serum
      irisin was positively correlated with MAMC and thigh circumference, but
      negatively correlated with residual renal function and cIMT. Multivariate
      analysis revealed that MAMC (per 1 cm increase, B = 8.78, 95% confidence interval
      [CI] = 0.77-16.79, P = 0.03) had an independent association with serum irisin. In
      addition, serum irisin was a significant independent predictor for carotid
      atherosclerosis even after adjustment for high-sensitivity C-reactive protein in
      PD patients (per 1 g/mL increase, odds ratio = 0.990, 95% CI = 0.982-0.997, P =
      0.007). CONCLUSION: This study demonstrated that serum irisin was significantly
      associated with sarcopenia and carotid atherosclerosis in PD patients. Additional
      studies to provide a confirmation and examine possible mechanisms are warranted.

PMID- 26298737
TI  - Selective inactivation of NADPH oxidase 2 causes regression of vascularization
      and the size and stability of atherosclerotic plaques.
AB  - BACKGROUND: A variety of NADPH oxidase (Nox) isoforms including Noxs 1, 2, 4 and
      5 catalyze the formation of reactive oxygen species (ROS) in the vascular wall.
      The Nox2 isoform complex has arguably received the greatest attention in the
      progression of atherogenesis in animal models. Thus, in the current study we
      postulated that specific Nox2 oxidase inhibition could reverse or attenuate
      atherosclerosis in mice fed a high-fat diet. METHODS: We evaluated the effect of
      isoform-selective Nox2 assembly inhibitor on the progression and vascularization
      of atheromatous plaques. Apolipoprotein E-deficient mice (ApoE-/-) were fed a
      high fat diet for two months and treated over 15 days with Nox2ds-tat or control
      sequence (scrambled); 10 mg/kg/day, i.p. Mice were sacrificed and superoxide
      production in arterial tissue was detected by cytochrome C reduction assay and
      dihydroethidium staining. Plaque development was evaluated and the angiogenic
      markers VEGF, HIF1-alpha and visfatin were quantified by real time qRT-PCR. MMP-9
      protein release and gelatinolytic activity was determined as a marker for
      vascularization. RESULTS: Nox2ds-tat inhibited Nox-derived superoxide determined
      by cytochrome C in carotid arteries (2.3 +/- 0.1 vs 1.7 +/- 0.1 O2(*-)
      nmol/min*mg protein; P < 0.01) and caused a significant regression in
      atherosclerotic plaques in aorta (66 +/- 6 MUm(2) vs 37 +/- 1 MUm(2); scrmb vs.
      Nox2ds-tat; P < 0.001). Increased VEGF, HIF-1alpha, MMP-9 and visfatin expression
      in arterial tissue in response to high-fat diet were significantly attenuated by
      Nox2ds-tat which in turn impaired both MMP-9 protein expression and activity.
      CONCLUSION: Given these results, it is quite evident that selective Nox
      inhibitors can reverse vascular pathology arising with atherosclerosis.

PMID- 26298740
TI  - Plaque microstructures in patients with coronary artery disease who achieved very
      low low-density lipoprotein cholesterol levels.
AB  - OBJECTIVE: Lowering low-density lipoprotein cholesterol (LDL-C) with statins
      reduces cardiovascular events and slows plaque progression. While this
      therapeutic approach has been reported to favorably modify plaque composition,
      this is not well characterized in humans. Also, the benefit of achieving LDL-C
      levels below current recommended targets remains unknown. Frequency-domain
      optical coherence tomography (FD-OCT) enables visualization of plaque
      microstructures associated with plaque instability. We investigated plaque
      morphologies in patients with low LDL-C levels by using FD-OCT. METHODS: 293 and
      122 non-obstructive lipid and fibrous plaques in 280 stable statin-treated CAD
      patients were evaluated by FD-OCT imaging in vessels requiring percutaneous
      coronary intervention. Study subjects were stratified according to achieved LDL-C
      levels (<50, 50-70, 70-100, <100 mg/dL). FD-OCT derived plaque microstructures
      were compared. RESULTS: LDL-C levels <50 mg/dL and <70 mg/dL were observed in
      13.9% (39/280) and 29.2% (82/280) of patients, respectively. Patients with LDL-C
      <50 mg/dL were more likely to be older (p < 0.001) and receive a high-dose statin
      (p = 0.01). On FD-OCT imaging, patients with LDL-C <50 mg/dL were more likely to
      have fibrous plaque (51.7, 43.2, 22.2 and 12.3%, p = 0.01) and less likely to
      have lipid plaques (48.2, 56.7, 77.7 and 87.6%, p = 0.01). In addition, LDL-C
      level was significantly associated with lipid arc (173 +/- 76, 175 +/- 88, 196 +/
      102 and 234 +/- 85 degrees , p = 0.01) and fibrous cap thickness (139.9 +/-
      93.9, 103.1 +/- 66.4, 92.5 +/- 48.5 and 92.1 +/- 47.8 um, p = 0.001). In
      particular, the smallest lipid arc and thickest fibrous cap were observed in
      patients who achieved LDL-C <50 mg/dL. Multivariable analysis revealed LDL-C
      levels (beta coefficient -0.254, p = 0.009) and high-dose statin use (beta
      coefficient 1.814, p = 0.003) to independently associate with fibrous cap
      thickness. CONCLUSIONS: More stable plaque features were observed within non
      obstructive atheromas in patients with very low LDL-C levels. These findings
      underscore LDL-C level to stabilize plaques in patients with CAD and high
      residual atherosclerotic risk.

PMID- 26298741
TI  - Lipoprotein (a) as a risk factor for ischemic stroke: a meta-analysis.
AB  - OBJECTIVE: Lipoprotein (a) [Lp(a)] harbors atherogenic potential but its role as
      a risk factor for ischemic stroke remains controversial. We conducted a meta
      analysis to determine the relative strength of the association between Lp(a) and
      ischemic stroke and identify potential subgroup-specific risk differences.
      METHODS: A systematic search using the MeSH terms "lipoproteins" OR "lipoprotein
      a" AND "stroke" was performed in PubMed and ScienceDirect for case-control
      studies from June 2006 and prospective cohort studies from April 2009 until
      December 20th 2014. Data from eligible papers published before these dates were
      reviewed and extracted from previous meta-analyses. Studies that assessed the
      relationship between Lp(a) levels and ischemic stroke and reported generic data
      i.e. odds ratio [OR], hazard ratio, or risk ratio [RR]-were eligible for
      inclusion. Studies that not distinguish between ischemic and hemorrhagic stroke
      and transient ischemic attack were excluded. Random effects meta-analyses with
      mixed-effects meta-regression were performed by pooling adjusted OR or RR.
      RESULTS: A total of 20 articles comprising 90,904 subjects and 5029 stroke events
      were eligible for the meta-analysis. Comparing high with low Lp(a) levels, the
      pooled estimated OR was 1.41 (95% CI, 1.26-1.57) for case-control studies (n =
      11) and the pooled estimated RR was 1.29 (95% CI, 1.06-1.58) for prospective
      studies (n = 9). Sex-specific differences in RR were inconsistent between case
      control and prospective studies. Study populations with a mean age of <=55 years
      had an increased RR compared to older study populations. Reported Lp(a) contrast
      levels and ischemic stroke subtype significantly contributed to the heterogeneity
      observed in the analyses. CONCLUSION: Elevated Lp(a) is an independent risk
      factor for ischemic stroke and may be especially relevant for young stroke
      patients. Sex-specific risk differences remain conflicting. Further studies in
      these subgroups may be warranted.

PMID- 26298739
TI  - Soluble klotho and mortality: the Ludwigshafen Risk and Cardiovascular Health
      Study.
AB  - BACKGROUND: Experimental evidence suggests that soluble klotho (s-klotho), a co
      receptor for fibroblast growth factor 23 (FGF23), may modulate cardiovascular
      risk through multiple mechanisms. However, the predictive value of s-klotho in
      patients remains unclear. Therefore, the present study examined in a large cohort
      of patients referred for coronary angiography whether s-klotho is associated with
      cardiovascular and total mortality. METHODS: The longitudinal associations
      between baseline s-klotho and FGF23 concentrations and mortality were evaluated
      in 2948 participants of the Ludwigshafen Risk and Cardiovascular Health Study
      (LURIC), referred for coronary angiography. RESULTS: Mean age of participants
      was: 63 +/- 10 years. Patients with diabetes mellitus (n = 1136) had elevated s
      klotho: [440 (430-449) versus 414 (406-421) pg/mL, p < 0.001]. S-klotho decreased
      in parallel to glomerular filtration rate (GFR) and increased in parallel to
      FGF23. During a median follow-up of 9.9 years, 874 deaths (30%) occurred, 539
      (18%) of which were cardiovascular. After adjustment for cardiovascular risk
      factors, the hazard ratios in the fourth quartile compared to the first quartile
      of s-klotho were 1.14 (95%CI, 0.94-1.38; p = 0.187) for all-cause mortality and
      1.03 (95%CI, 0.80-1.31; p = 0.845) for cardiovascular mortality. Excess mortality
      prediction by high levels of baseline FGF23 was not modified by adjustment for
      baseline s-klotho levels. CONCLUSIONS: Klotho does not add predictive power to
      cardiovascular and mortality risk assessment in patients with normal renal
      function.

PMID- 26298742
TI  - Lipoprotein(a)-lowering therapies: a double edged sword?

PMID- 26298743
TI  - IL-22 affects smooth muscle cell phenotype and plaque formation in apolipoprotein
      E knockout mice.
AB  - OBJECTIVE: IL-22 is a recently discovered cytokine that belongs to the family of
      IL-10 related cytokines. It is produced by activated T-cells and innate lymphoid
      cells and has been suggested to be involved in tissue repair. As both
      inflammation and repair play important roles in atherosclerosis we investigated
      if IL-22 deficiency influences the disease process in Apoe(-/-) mice. METHODS: We
      generated IL-22(-/-)Apoe(-/-) mice and fed them high-fat-diet for 14 weeks to
      characterize atherosclerosis development. RESULTS: IL-22(-/-)Apoe(-/-) mice
      exhibited reduced plaque size both in the aorta (p = 0.0036) and the aortic root
      compared (p = 0.0012) with Apoe(-/-) controls. Moreover, plaque collagen was
      reduced in IL-22(-/-)Apoe(-/-) mice (p = 0.02) and this was associated with an
      increased expression of smooth muscle cell (SMC)-alpha-actin (p = 0.04) and
      caldesmon (p = 0.016) in the underlying media. Carotid arteries from IL-22(-/
      )Apoe(-/-) mice displayed increased expression of genes associated with a
      contractile SMC phenotype e.g. alpha-actin (p = 0.004) and caldesmon (p = 0.03).
      Arterial SMCs were shown to express the IL-22 receptor and in vitro exposure to
      IL-22 resulted in a down-regulation of alpha actin and caldesmon gene expression
      in these cells. CONCLUSION: Our observations demonstrate that IL-22 is involved
      in plaque formation and suggest that IL-22 released by immune cells is involved
      in activation of vascular repair by stimulating medial SMC dedifferentiation into
      a synthetic phenotype. This response contributes to plaque growth by enabling SMC
      migration into the intima but may also help to stabilize the plaque.

PMID- 26298744
TI  - Colorectal adenoma is associated with coronary artery calcification in a Korean
      population.
AB  - OBJECTIVE: Colorectal adenoma and coronary atherosclerosis have similar risk
      factors. The aim of this study was to investigate the association between
      colorectal adenoma and coronary artery calcification (CAC), which is used as a
      surrogate marker for coronary atherosclerosis. METHODS: This is a cross-sectional
      study of 398 Koreans (290 males, mean age of 56.8 +/- 8.1 years) who underwent
      CAC scoring by multi-slice computed tomography and colonoscopy on the same day as
      the screening examination. The CAC scores were divided into the following three
      categories according to severity: absent (CAC score = 0), mild (0 < CAC score <=
      100), and moderate-to-severe CAC (CAC score > 100). RESULTS: Colorectal adenoma
      was detected in 149 (37.4%) subjects and was significantly associated with a CAC
      score of >0 (OR = 1.66, 95% CI = 1.05-2.64, P = 0.032), including both mild (OR =
      1.80, 95% CI = 1.06-3.03, P = 0.029) and moderate-to-severe CAC (OR = 1.95, 95%
      CI = 1.05-3.63, P = 0.035), in multivariate analysis after adjusting for age,
      gender and other risk factors. The proportion of subjects with colorectal adenoma
      and advanced adenoma progressively increased with increasing CAC score
      (colorectal adenoma 28.9%-54.1%, P for trend < 0.001; advanced adenoma 7.0%
      16.4%, P for trend = 0.026). CONCLUSION: Colorectal adenoma is related to
      coronary artery calcification independent of traditional risk factors for
      asymptomatic Koreans. The prevalence of advanced adenoma is more common in
      individuals with severe coronary atherosclerosis.

PMID- 26298745
TI  - Association between Dictyocaulus viviparus status and milk production parameters
      in Dutch dairy herds.
AB  - The objective of this study was to estimate the association between Dictyocaulus
      viviparus bulk tank milk (BTM) test results and milk production and milk
      composition parameters in adult Dutch dairy cattle herds. Bulk tank milk samples
      were collected in August and November 2013, and ELISA tests were performed. Two
      hundred BTM positive (BTM+) and 200 BTM negative (BTM-) herds were selected based
      on their BTM test result of November 2013, obtained from a list of farms that
      participated in the Dutch GD Animal Health voluntary monitoring program for
      controlling nematode infections. The relationship between D. viviparus BTM status
      and 3 production parameters (milk production, milk fat %, and milk protein %) in
      summer (June to August 2013) and autumn (September and October 2013) was
      investigated using generalized linear mixed models. Production data were
      available for 126 BTM- herds and 109 BTM+ herds. Results showed that a positive
      D. viviparus status was associated with decreased milk production (June: -1.01,
      July: -1.19, August: -1.68, September and October: -1.33kg/cow per d). Milk fat
      percentage was 0.14% and 0.08% lower during summer and autumn, respectively, in
      BTM+ herds. No significant association was demonstrated between a positive BTM
      test result and milk protein percentage. Because a strong correlation was present
      between the BTM status for D. viviparus and that for Ostertagia ostertagi, these
      losses cannot be attributed to one of the two parasites. However, it is clear
      that these parasite infections have a considerable effect on production. 

PMID- 26298746
TI  - Acute brief heat stress in late gestation alters neonatal calf innate immune
      functions.
AB  - Heat stress, as one of the environmental stressors affecting the dairy industry,
      compromises the cow milk production, immune function, and reproductive system.
      However, few studies have looked at how prenatal heat stress (HS) affects the
      offspring. The objective of this study was to evaluate the effect of HS during
      late gestation on calf immunity. Calves were born to cows exposed to evaporative
      cooling (CT) or HS (cyclic 23-35 degrees C) for 1 wk at 3 wk before calving. Both
      bull and heifer calves (CT, n=10; HS, n=10) were housed in similar environmental
      temperatures after birth. Both CT and HS calves received 3.78 L of pooled
      colostrum within 12 h after birth and were fed the same diet throughout the
      study. In addition to tumor necrosis factor alpha, IL-1beta, IL-1 receptor
      antagonist (IL-1RA), and toll-like receptor (TLR)2, and TLR4 mRNA expression, the
      expression of CD14(+) and CD18(+) cells, and DEC205(+) dendritic cells were
      determined in whole blood samples at d 0, 3, 7, 14, 21, and 28. The neutrophil to
      lymphocyte ratio, differential cell counts, and the hematocrit were also
      determined. During late gestation, the HS cows had greater respiration rates,
      rectal temperatures, and tended to spend more time standing compared with the CT
      cows. The HS calves had less expression of tumor necrosis factor-alpha and TLR2
      and greater levels of IL-1beta, IL-1RA, and TLR4 compared with CT calves. The HS
      calves also had a greater percentage of CD18(+) cells compared with the CT
      calves. Additionally, a greater percentage of neutrophils and lesser percentage
      of lymphocytes were in the HS calves compared with the CT calves. The results
      indicate that biomarkers of calves' immunity are affected in the first several
      weeks after birth by HS in the dam during late gestation. 

PMID- 26298747
TI  - Modification of the Kjeldahl noncasein nitrogen method to include bovine milk
      concentrates and milks from other species.
AB  - The objective of our research was to modify the current indirect casein method
      for bovine milk to enable it to be applied to bovine milk, bovine milk
      concentrates, and milks of other species that contain a protein concentration up
      to 9% (wt/wt). Our work used a series of bovine milk concentrates from about 3 to
      9% protein with the same casein as a percentage of true protein to determine the
      amount of buffer required and pH of the noncasein nitrogen (NCN) filtrate to
      achieve consistent estimates of casein and casein as percent of true protein. As
      the concentration of protein in milk increased (either in bovine milk
      concentrates or in milks of other species), the amount of buffer needed for the
      NCN sample preparation method to achieve a filtrate pH of 4.6 increased. In the
      first part of the study using a series of bovine milk concentrates, it was
      demonstrated that the method gave more consistent predictions of casein as a
      percentage of true protein when the final NCN filtrate pH was between 4.5 and 4.6
      at 38 degrees C. When the amount of buffer added to the sample was not sufficient
      (i.e., the filtrate pH was too high), the filtrates were not clear. A polynomial
      equation was developed for prediction of the amount of acetic acid or sodium
      acetate buffer required to achieve pH 4.5 to 4.6 for milk protein concentrations
      from 3 to 9% protein using bovine milk and milk concentrates. When the equation
      developed using cow milk was applied to goat, sheep, and water buffalo milks, it
      correctly predicted the volume of reagents needed to achieve a final NCN filtrate
      pH of 4.6 at 38 degrees C. We also verified as part of this work that the ability
      to measure NPN content of milk was not influenced by protein content of milk in
      the range from 3 to 9% protein. The results of this study will be used as the
      basis for proposed changes in the official methods for measurement of the casein
      content of milk to expand the scope of the method so it can be used to achieve
      accurate results for milk concentrates and milks of other species. 

PMID- 26298748
TI  - Textural and cooking properties and viscoelastic changes on heating and cooling
      of Balkan cheeses.
AB  - The growth in food service and prepared consumer foods has led to increasing
      demand for cheese with customized textural and cooking characteristics. The
      current study evaluated Kackavalj, Kackavalj Krstas, and Trappist cheeses
      procured from manufacturing plants in Serbia for texture profile characteristics,
      flow and extensibility of the heated cheese, and changes in viscoelasticity
      characteristics during heating and cooling. Measured viscoelastic parameters
      included elastic modulus, G', loss modulus, G", and loss tangent, LT (G"/G'). The
      melting temperature and congealing temperature were defined as the temperature at
      which LT=1 during heating from 25 to 90 degrees C and on cooling from 90 to 25
      degrees C. The maximum LT during heating was as an index of the maximum fluidity
      of the molten cheese. Significant variation was noted for the extent of flow and
      extensibility of the heated cheeses, with no trend of cheese type. As a group,
      the Kackavalj cheeses had relatively high levels of salt-in-moisture and pH 4.6
      soluble N and low protein-to-fat ratio and levels of alphas1-CN (f24-199). They
      fractured during compression to 75%; had relatively low values of cohesiveness,
      chewiness, and springiness; melted at ~70 to 90 degrees C; reached maximum LT at
      90 degrees C; and congealed at 58 to 63 degrees C. Conversely, the Kackavalj
      Krstas and Trappist cheeses had low levels of primary proteolysis and salt-in
      moisture content and a high protein-to-fat ratio. They did not fracture during
      compression, had high values for cohesiveness and chewiness, melted at lower
      temperatures (56-62 degrees C), attained maximum fluidity at a lower temperature
      (72-78 degrees C), and congealed at 54 to 69 degrees C. There was a hysteretic
      dependence of G' and LT on temperature for all cheeses, with the LT during
      cooling being higher than that during heating, and G' during cooling being lower
      or higher than the equivalent values during heating depending on the cheese type.
      Monitoring the dynamic changes in viscoelasticity during heating and cooling of
      the cheese in the temperature range 25 to 90 degrees C provides a potentially
      useful means of designing ingredient cheeses, with the desired attributes when
      heated and cooled under customized specification. 

PMID- 26298749
TI  - Effects of intramuscular administration of folic acid and vitamin B12 on
      granulosa cells gene expression in postpartum dairy cows.
AB  - The fertility of dairy cows is challenged during early lactation, and better
      nutritional strategies need to be developed to address this issue. Combined
      supplementation of folic acid and vitamin B12 improve energy metabolism in the
      dairy cow during early lactation. Therefore, the present study was undertaken to
      explore the effects of this supplement on gene expression in granulosa cells from
      the dominant follicle during the postpartum period. Multiparous Holstein cows
      received weekly intramuscular injection of 320 mg of folic acid and 10 mg of
      vitamin B12 (treated group) beginning 24 (standard deviation=4) d before calving
      until 56 d after calving, whereas the control group received saline. The urea
      plasma concentration was significantly decreased during the precalving period,
      and the concentration of both folate and vitamin B12 were increased in treated
      animals. Milk production and dry matter intake were not significantly different
      between the 2 groups. Plasma concentrations of folates and vitamin B12 were
      increased in treated animals. Daily dry matter intake was not significantly
      different between the 2 groups before [13.5 kg; standard error (SE)=0.5] and
      after (23.6 kg; SE=0.9) calving. Average energy-corrected milk tended to be
      greater in vitamin-treated cows, 39.7 (SE=1.4) and 38.1 (SE=1.3) kg/d for treated
      and control cows, respectively. After calving, average plasma concentration of
      beta-hydroxybutyrate tended to be lower in cows injected with the vitamin
      supplement, 0.47 (SE=0.04) versus 0.55 (SE=0.03) for treated and control cows,
      respectively. The ovarian follicle >=12 mm in diameter was collected by ovum pick
      up after estrus synchronization. Recovered follicular fluid volumes were greater
      in the vitamin-treated group. A microarray platform was used to investigate the
      effect of treatment on gene expression of granulosa cells. Lower expression of
      genes involved in the cell cycle and higher expression of genes associated with
      granulosa cell differentiation before ovulation were observed. Selected candidate
      genes were analyzed by reverse transcription quantitative PCR. Although the
      effects of intramuscular injections of folic acid and vitamin B12 on lactational
      performance and metabolic status of animals were limited, ingenuity pathway
      analysis of gene expression in granulosa cells suggests a stimulation of cell
      differentiation in vitamin-treated cows, which may be the result of an increase
      in LH secretion. 

PMID- 26298750
TI  - Adipocyte differentiation-related protein promotes lipid accumulation in goat
      mammary epithelial cells.
AB  - Milk fat originates from the secretion of cytosolic lipid droplets (CLD)
      synthesized within mammary epithelial cells. Adipocyte differentiation-related
      protein (ADRP; gene symbol PLIN2) is a CLD-binding protein that is crucial for
      synthesis of mature CLD. Our hypothesis was that ADRP regulates CLD production
      and metabolism in goat mammary epithelial cells (GMEC) and thus plays a role in
      determining milk fat content. To understand the role of ADRP in ruminant milk fat
      metabolism, ADRP (PLIN2) was overexpressed or knocked down in GMEC using an
      adenovirus system. Immunocytochemical staining revealed that ADRP localized to
      the surface of CLD. Supplementation with oleic acid (OA) enhanced its
      colocalization with CLD surface and enhanced lipid accumulation. Overexpression
      of ADRP increased lipid accumulation and the concentration of triacylglycerol in
      GMEC. In contrast, morphological examination revealed that knockdown of ADRP
      decreased lipid accumulation even when OA was supplemented. This response was
      confirmed by the reduction in mass of cellular TG when ADRP was knocked down. The
      fact that knockdown of ADRP did not completely eliminate lipid accumulation at a
      morphological level in GMEC without OA suggests that some other compensatory
      factors may also aid in the process of CLD formation. The ADRP reversed the
      decrease of CLD accumulation induced by adipose triglyceride lipase. This is
      highly suggestive of ADRP promoting triacylglycerol stability within CLD by
      preventing access to adipose triglyceride lipase. Collectively, these data
      provide direct in vitro evidence that ADRP plays a key role in CLD formation and
      stability in GMEC. 

PMID- 26298751
TI  - The dopamine antagonist domperidone increases prolactin concentration and
      enhances milk production in dairy cows.
AB  - In previous studies, our team showed that the inhibition of prolactin (PRL)
      secretion by the dopamine agonist quinagolide reduces milk production in dairy
      cows. The objective of this study was to determine the effects of administration
      of a dopamine antagonist on basal and milking-induced PRL concentrations in blood
      and on milk production during positive energy balance and feed restriction in
      dairy cows. Eighteen mid-lactation Holstein cows received daily s.c. injections
      of either domperidone (300 mg, DOMP, n=9) or the vehicle, canola oil (CTL, n=9),
      for 5 wk. During wk 5, all cows were fed at 65% of their dry matter intake in the
      previous week. Blood and milk samples were collected before (for blood) and
      during (for milk) the a.m. milking thrice weekly from d -9 to 41 (8d after the
      last injection). In addition, blood samples were collected during the a.m.
      milking on d -1 (before the first injection), and on d 1, 28, and 34. Basal PRL
      concentration was similar in both groups before the start of the treatments.
      Domperidone injections caused a gradual increase in basal PRL concentration. Feed
      restriction reduced basal PRL concentration in both the CTL and DOMP cows, but
      PRL concentration remained higher in the DOMP cows. Prolactin concentration
      remained elevated in the DOMP cows 7d after the last injection. The milk
      concentration of PRL increased during the DOMP treatment, but the increase was
      smaller than that observed in serum. In the CTL cows, the milking-induced PRL
      release above the premilking concentration was similar on d -1, 1, and 28 but was
      reduced during feed restriction. In the DOMP cows, the milking-induced PRL
      release was similar on d -1 and 1 but was reduced on d 28 and 34. Milk production
      was similar for both groups before the treatments started but was greater in the
      DOMP cows during the treatment period, at 2.9 +/- 0.6 and 2.4 +/- 0.6 kg/d
      greater during wk 3 and 4 of treatment, respectively. Milk production declined in
      both groups during feed restriction but remained higher in the DOMP cows. Milk
      production became similar again for both groups after the last injection. In
      addition, dry matter intake was increased by DOMP. These results support the
      hypothesis that PRL is galactopoietic in dairy cattle.

PMID- 26298752
TI  - The effects of postexercise consumption of a kefir beverage on performance and
      recovery during intensive endurance training.
AB  - This study was designed to determine whether kefir accentuates the positive
      health benefits assessed by measures in fitness, body composition, or both, as a
      measure of cardiovascular disease risk as well as the biomarker C-reactive
      protein (CRP). Sixty-seven adult males and females aged 18 to 24 yr were assigned
      to 1 of 4 groups: (1) endurance training + control beverage, (2) endurance
      training +kefir beverage,(3) active control + control beverage, or (4) active
      control + kefir beverage. The exercise groups completed 15 wk of structured
      endurancetraining while the active control groups maintained their usual exercise
      routine. Additionally, each group was assigned to either a kefir or a
      calorie/macronutrient matched placebo beverage that was consumed twice per week.
      No significant interactions were found among groups with respect to outcome
      variables with the exception of serum CRP. The endurance training was effective
      in improving 1.5-mile (2.41 km) times and kefir supplementation may have been a
      factor in attenuating the increase in CRP that was observed over the course of
      the intervention period. This preliminary study suggests that kefir may be
      involved in improving the risk profile for cardiovascular disease as defined by
      CRP.

PMID- 26298753
TI  - Late blowing of Cheddar cheese induced by accelerated ripening and ribose and
      galactose supplementation in presence of a novel obligatory heterofermentative
      nonstarter Lactobacillus wasatchensis.
AB  - Lactobacillus wasatchensis sp. nov. has been studied for growth and gas formation
      in a control Cheddar cheese and in cheese supplemented with 0.5% ribose, 0.5%
      galactose, or 0.25% ribose plus 0.25% galactose using regular and accelerated
      cheese ripening temperatures of 6 and 12 degrees C, respectively. Milk was
      inoculated with (1) Lactococcus lactis starter culture, or (2) Lc. lactis starter
      culture plus Lb. wasatchensis (10(4) cfu/mL). In the control cheese with no added
      Lb. wasatchensis, starter numbers decreased from 10(7) initially to ~10(4) cfu/g
      over 23 wk of ripening at 6 degrees C. When the cheese was ripened at 12 degrees
      C, or if Lb. wasatchensis was added, the final starter counts were 1 log lower.
      In contrast, nonstarter lactic acid bacteria in the cheese increased from <10(2)
      cfu/g at press to 10(6) to 10(7) cfu/g after 23 wk, with higher numbers being
      observed with ripening at 12 degrees C. In cheese with no added Lb. wasatchensis,
      levels of Lb. wasatchensis were initially below the enumeration threshold but
      counts of up to 10(3) cfu/g were detected after 23 wk. When the cheese was
      inoculated with Lb. wasatchensis, it could be enumerated throughout ripening,
      with final levels at 23 wk being dependent on whether ribose had been added to
      the cheese curd. With added ribose (with or without added galactose), Lb.
      wasatchensis grew to 10(7) to 10(8) cfu/g after 23 wk, whereas without added
      ribose it was 1 log lower. In all cheeses with added Lb. wasatchensis, greater
      gas formation was observed at 12 degrees C, with most gas production occurring
      after ~16 wk. Very little gas production was detected in cheese without added Lb.
      wasatchensis ripened at 12 degrees C or in cheese with added Lb. wasatchensis
      ripened at 6 degrees C. Adding a combination of ribose and galactose caused more
      gas formation, putatively because of the ability of Lb. wasatchensis to co
      utilize both sugars and grow to high numbers, and then produce gas from galactose
      as ribose levels were depleted. Even without sugar supplementation, gas was
      observed in cheese with added Lb. wasatchensis after 16 wk. We also observed that
      Lb. wasatchensis could grow to high cell densities when grown in carbohydrate
      restricted broth containing lactococcal cell lysate. This suggests that during
      cheese ripening, lysis of starter bacteria provides sufficient substrates (such
      as ribose) to allow growth of Lb. wasatchensis and, if fermentable hexose is
      available, the cheese will become gassy. We conclude that Lb. wasatchensis is a
      previously undetected contributor to late gas formation in Cheddar cheese and the
      defect is more pronounced when elevated ripening temperatures are used. 

PMID- 26298754
TI  - Risk factors for the occurrence of new and chronic cases of subclinical mastitis
      in dairy herds in southern Brazil.
AB  - The aim of this research was to evaluate the risk factors for new and chronic
      subclinical intramammary infections (IMI) using the monthly somatic cells count
      of dairy cows. The study took place at 30 dairy herds with approximately 1,700
      cows in lactation. Data characterizing the dairy farms and their milking
      management were obtained from a survey questionnaire. The somatic cells count
      values from 2 consecutive months were used to classify cows as either healthy or
      with new or chronic infections. A chi-squared test was used in the analysis of
      subclinical IMI to evaluate associations between each independent variable,
      followed by logistic regression to estimate the risk of a new infection in
      healthy cows and of chronic infection in cows with new infections. Factors
      increasing the odds ratio of a cow developing a new case of subclinical mastitis
      were (1) cows with more than 3 lactations, (2) cows with a mean hyperkeratosis
      score above 3, (3) cows with the udder below the hock, (4) cows with very dirty
      udders, and (5) milking of infected animals before healthy cows. Factors
      increasing the risk of a subclinical chronic infection compared with new cases of
      subclinical mastitis were (1) a lack of regular maintenance of milking machinery,
      (2) cows over 100 d in lactation, and (3) cows with the udder on or below the
      hock. The risk factors identified in this study can be used in IMI control
      programs to reduce the frequency of new and chronic cases of subclinical
      mastitis. 

PMID- 26298755
TI  - Linseed oil supplementation to dairy cows fed diets based on red clover silage or
      corn silage: Effects on methane production, rumen fermentation, nutrient
      digestibility, N balance, and milk production.
AB  - The objective of this study was to examine the effect of linseed oil (LO)
      supplementation to red clover silage (RCS)- or corn silage (CS)-based diets on
      enteric CH4 emissions, ruminal fermentation characteristics, nutrient
      digestibility, N balance, and milk production. Twelve rumen-cannulated lactating
      cows were used in a replicated 4*4 Latin square design (35-d periods) with a 2*2
      factorial arrangement of treatments. Cows were fed (ad libitum) RCS- or CS-based
      diets [forage:concentrate ratio 60:40; dry matter (DM) basis] without or with LO
      (4% of DM). Supplementation of LO to the RCS-based diet reduced enteric CH4
      production (-9%) and CH4 energy losses (-11%) with no adverse effects on DM
      intake, digestion, ruminal fermentation characteristics, protozoa numbers, or
      milk production. The addition of LO to the CS-based diet caused a greater
      decrease in CH4 production (-26%) and CH4 energy losses (-23%) but was associated
      with a reduction in DM intake, total-tract fiber digestibility, protozoa numbers,
      acetate:propionate ratio, and energy-corrected milk yield. Urinary N excretion
      (g/d) decreased with LO supplementation to RCS- and CS-based diets, suggesting
      reduced potential of N2O emissions. Results from this study show that the
      depressive effect of LO supplementation on enteric CH4 production is more
      pronounced with the CS- than with the RCS-based diet. However, because of reduced
      digestibility with the CS-based diet, the reduction in enteric CH4 production may
      be offset by higher CH4 emissions from manure storage. Thus, the type of forage
      of the basal diet should be taken into consideration when using fat
      supplementation as a dietary strategy to reduce enteric CH4 production from dairy
      cows. 

PMID- 26298756
TI  - Blood-derived proteins in milk at start of lactation: Indicators of active or
      passive transfer.
AB  - Colostrum has a different composition compared with milk in established
      lactation. This difference is in part due to the partially open blood-milk
      barrier, which, when closed, is designed to prevent the interdiffusion of blood
      and milk components. In the first days of lactation, alpha-lactalbumin (alpha
      LA), a milk protein, is typically present in blood and several blood-derived
      proteins are also present in milk, such as IgG1, IgG2, serum albumin (SA), and
      lactate dehydrogenase (LDH). With the exception of IgG1, which is known to be
      transferred by active transcellular transport, the other proteins are thought to
      pass paracellularly through the temporarily open barrier. Along with an exchange
      of blood and milk components, somatic cell count (SCC) is typically high in
      colostrum. The decline of these proteins and SCC can be used as indicators to
      determine transcellular or paracellular transport. Two hypotheses were tested.
      The first hypothesis was that the decline curve for a protein or SCC would be the
      same as IgG1, indicating transcellular transport, or the decline curve would be
      different than IgG1, indicating paracellular transport. The second hypothesis was
      that the decline curves of SCC and all proteins that are thought to have
      paracellular transport would be the same. Ten Holstein cows were milked at 4 h
      after parturition, the next 5 consecutive milkings, and the afternoon milking on
      d 5, 8, 10, and 14 of lactation for a total of 10 milking time points, and
      sequential jugular blood samples were also taken. Blood and milk samples were
      analyzed for the concentrations of LDH, SA, IgG1, IgG2, and alpha-LA and milk
      samples were measured for SCC. Protein concentration and SCC curves were
      generated from all 10 time points and were evaluated using the tau time constant
      model to determine the rate of decline of the slope of each protein. When
      examining the first hypothesis, the concentration of IgG1 declined significantly
      faster in the milk than the proteins IgG2 and LDH, but declined at the same rate
      as SA. Immunoglobulin G1 also declined significantly faster than SCC and alpha-LA
      in plasma. The second hypothesis showed that IgG2, LDH, and SA in milk were
      declining at the same rate, but were declining significantly faster than SCC and
      alpha-LA in plasma. These results indicate that only active transcellular
      transport of IgG1 occurred, with a sharp decline at parturition, compared with
      IgG2, SA, LDH, alpha-LA, and SCC, which are likely following paracellular
      transport. 

PMID- 26298757
TI  - Effects of high concentrations of dietary crude glycerin on dairy cow
      productivity and milk quality.
AB  - An increasing worldwide interest in alternative fuel sources and in a more
      diversified energy matrix has provided incentives for the biodiesel industry,
      generating large amounts of the by-product crude glycerin, a potential
      alternative feed for dairy cows. A replicated 3*3 Latin square study was
      conducted to evaluate the effects of high concentrations of crude glycerin on dry
      matter intake, milk yield and composition, milk fatty acid profile, and blood
      metabolites of medium-yield cows. Ruminally cannulated Holstein cows (n=6; 587 +/
      39 kg of body weight; 114 +/- 29 d in milk; and 20 +/- 1.5 kg/d milk yield) were
      used in the study. The experimental period included 2 wk for adaptation and 1 wk
      for data collection. Cows were fed diets containing 0 (control), 15, or 30% crude
      glycerin (83% glycerol). Cows were milked, milk weights were recorded twice
      daily, and milk samples were collected for milk quality analyses at d 18 and 19
      in each experimental period. Feeding cows with crude glycerin linearly decreased
      dry-matter intake, the 3.5% fat-corrected milk, and the solid-corrected milk
      yield. Hepatic enzymes were not affected by dietary treatments, except gamma
      glutamyl transferase, which was decreased with the 15% crude glycerin diet. Serum
      glucose and albumin showed quadratic effect with increasing inclusion of crude
      glycerin. Plasma cholesterol as well as total protein linearly decreased with
      increasing inclusion of crude glycerin. Milk fat concentration and yield showed a
      quadratic effect of treatments. Solid yield decreased linearly with increasing
      inclusion of crude glycerin. Odd-chain fatty acids and conjugated linoleic acid
      in milk fat linearly increased with addition of crude glycerin in the diets.
      Together, these results suggest that crude glycerin has potential to replace
      corn; however, feeding diets in which corn is replaced with crude glycerin at 30%
      of dietary DM greatly reduces animal performance.

PMID- 26298758
TI  - Effect of crofelemer extract on severity and consistency of experimentally
      induced enterotoxigenic Escherichia coli diarrhea in newborn Holstein calves.
AB  - The objective of this study was to evaluate the effect of a standardized
      botanical extract of Croton lechleri, named crofelemer extract, on fecal dry
      matter and fecal scores on diarrheic newborn Holstein bull calves induced by
      enterotoxigenic Escherichia coli. A double-blinded randomized clinical trial was
      performed in which 60 newborn Holstein bull calves were clean caught and
      transported to an isolation facility where calves were individually housed and
      randomly assigned to 1 of 3 treatment groups: placebo (control), enteric-coated
      formulation of crofelemer extract (ECROF), and nonenteric-coated formulation of
      crofelemer extract (CROF). Diarrhea was induced at first feeding with an inoculum
      of the enterotoxigenic Escherichia coli (ATCC 31616) administered with a third of
      the recommended dose of a colostrum replacer. All calves enrolled in this study
      received treatments starting on the second feeding (diarrhea onset) and
      treatments were administered before feeding time (0600 and 1600h) for 6 feedings
      consecutively. All calves in this study had failure of passive transfer. The only
      cause of death in this study was due to septicemia, accounting for 1 death out of
      each treatment group. All the calves were examined twice daily, within 2h after
      feeding, from d 1 (prechallenge) until 10, on d 15, and a last examination on d
      25 of life. Five parameters were evaluated during each examination; rectal
      temperature, clinical assessment of dehydration status, fecal scores, attitude,
      and appetite. No differences were observed between treatment groups for rectal
      temperature, attitude, and appetite. Fecal dry matter was analyzed as
      prechallenge fecal dry matter, dry matter during treatment, and fecal dry matter
      after treatment cessation. No difference in prechallenge fecal dry matter was
      observed and prechallenge fecal dry matter was used as a covariate in the models.
      Fecal dry matter during treatment was significantly higher for ECROF calves when
      compared with control calves and CROF calves. Additionally, ECROF fecal dry
      matter after treatment cessation had a statistical tendency to be higher when
      compared with control calves. Together, these results suggest that enteric-coated
      formulation of the standardized crofelemer extract, a natural-product with
      antisecretory properties, can significantly increase fecal dry matter of neonatal
      calves with experimentally induced enterotoxigenic Escherichia coli diarrhea.
      More research is needed to test the efficacy of enteric-coated crofelemer on
      incidence and severity of secretory diarrhea on calves under natural challenge
      conditions. 

PMID- 26298759
TI  - Effect of soluble calcium and lactose on limiting flux and serum protein removal
      during skim milk microfiltration.
AB  - The tendency of calcium to promote microfiltration (MF) membrane fouling is well
      documented, but the role of lactose has not been studied. Milk protein
      concentrate that is 85% protein on a dry basis (MPC85) contains less calcium and
      lactose than skim milk. Our objectives were to determine the effects of skim milk
      soluble calcium and lactose concentrations on the limiting fluxes (LF) and serum
      protein (SP) removal factors of 0.1-um ceramic graded permeability membranes. The
      MF was fed with 3 different milks: skim milk, liquid MPC85 that had been
      standardized to the protein content of skim milk with reverse osmosis water
      (MPC), and liquid MPC85 that had been standardized to the protein and lactose
      contents of skim milk with reverse osmosis water and lactose monohydrate (MPC+L).
      Retentate and permeate were continuously recycled to the feed tank. The LF for
      each feed was determined by increasing flux once per hour from 55 kg.m(-2).h(-1)
      until flux did not increase with increasing transmembrane pressure. Temperature,
      pressure drop across the membrane length, and protein concentration in the
      retentate recirculation loop were maintained at 50 degrees C, 220 kPa, and 8.77
      +/- 0.2%, respectively. Experiments were replicated 3 times and the Proc GLM
      procedure of SAS was used for statistical analysis. An increase in LF between
      skim milk (91 kg.m(-2).h(-1)) and MPC+L (124 kg.m(-2).h(-1)) was associated with
      a reduction in soluble calcium. The LF of MPC+L was lower than the LF of MPC (137
      kg.m(-2).h(-1)) due to the higher viscosity contributed by lactose. Permeates
      produced from the MPC and MPC+L contained more protein than the skim milk
      permeate due to the transfer of caseins from the micelles into the reduced
      calcium sera of the MPC and MPC+L. A SP removal factor was calculated by dividing
      true protein in the permeate by SP in the permeate portion of the feed to
      describe the ease of SP passage through the membrane. No differences in SP
      removal factors were detected among the 3 feeds below the LF. As the fluxes
      approached the LF, SP removal factors decreased due to fouling. Feeding a MF
      system with MPC instead of skim milk will reduce the required membrane surface
      area, but the permeate protein composition will be slightly higher in casein
      content.

PMID- 26298760
TI  - Short communication: Subtyping of Staphylococcus haemolyticus isolates from milk
      and corresponding teat apices to verify the potential teat-skin origin of
      intramammary infections in dairy cows.
AB  - Coagulase-negative staphylococci (CNS) are a major cause of intramammary
      infections (IMI) in dairy cows and they colonize the teat skin. Staphylococcus
      haemolyticus, one of the more common CNS, has been identified as a highly
      versatile opportunistic species. The aim of the present study was to gain better
      insight into the adaptation of S. haemolyticus subtypes to the udder ecosystem
      with respect to IMI development. During a longitudinal observational study
      conducted over 13 mo on 6 Flemish dairy herds, S. haemolyticus isolates were
      recovered from milk and teat apices. A total of 44 S. haemolyticus isolates
      originating from milk (24 isolates) and teat apices (20 isolates) of 6 selected
      udder quarters were singled out and analyzed using a combined methodology of
      (GTG)5-PCR and amplified fragment length polymorphism (AFLP) fingerprinting to
      determine intraspecies differences. Combining both fingerprinting methods, 4 S.
      haemolyticus subtypes were obtained (I to IV). Subtypes I, II, and IV were
      recovered from both milk and teat apex samples and were found to be associated
      with persisting IMI. Subtype III, not apparently related to IMI, was isolated
      solely from teat apices and not from milk. In general, S. haemolyticus subtypes
      found in milk from infected quarters could be recovered from the corresponding
      teat apices, although the latter could be colonized with up to 3 different
      subtypes. Comparing subtypes from milk and teat apices indicates that the IMI
      causing agent likely originates from the teat skin. 

PMID- 26298761
TI  - Association of bedding types with management practices and indicators of milk
      quality on larger Wisconsin dairy farms.
AB  - The objective of this study was to identify associations of bedding type and
      selected management practices with bulk milk quality and productivity of larger
      Wisconsin dairy farms. Dairy herds (n=325) producing >=11,340 kg of milk daily
      were surveyed during a single farm visit. Monthly bulk milk SCC and total
      bacteria counts were obtained from milk buyers for 255 farms for a 2-yr period.
      Of farms with the same type of bedding in all pens during the study period, most
      used inorganic bedding (IB), followed by organic nonmanure bedding (OB) and
      manure products (MB). Almost all bulk milk total bacterial counts were <10,000
      cfu/mL and total bacterial count was not associated with bedding type. Bulk milk
      somatic cell score (BMSCS) was least for farms using IB, varied seasonally, and
      was greatest in the summer. The BMSCS was reduced when new bedding was added to
      stalls at intervals greater than 1 wk and when teats were dried before attaching
      the milking unit. The BMSCS for farms using OB was reduced when bedding in the
      backs of stalls was removed and replaced regularly and when fewer cows with
      nonfunctioning mammary quarters were present. The BMSCS for farms using MB was
      reduced when the proportion of cows with milk discarded was less. The rolling
      herd average (RHA) of herds using IB was 761 and 1,153 kg greater than the RHA of
      herds using OB and MB, respectively. The RHA was 353 kg greater on farms where
      farmers understood subclinical mastitis and 965 kg greater on farms milking 3
      times daily. Each 1% increase of cows with nonfunctioning mammary quarters was
      associated with a decrease of 57 kg of RHA. The BMSCS, proportions of cows with
      milk discarded and proportion of cows with nonfunctioning mammary quarters were
      least for herds using IB and were associated with increased productivity. Large
      Wisconsin dairy farms that used inorganic bedding had greater productivity and
      better milk quality compared with herds using other bedding types.

PMID- 26298762
TI  - Growth performance and sorting characteristics of corn silage-alfalfa haylage
      diets with or without forage dilution offered to replacement Holstein dairy
      heifers.
AB  - Gravid heifers consuming high-quality forage diets are susceptible to excessive
      weight gains and overconditioning. One approach for controlling this problem is
      to dilute diets with low-energy forages, such as straw, that reduce the caloric
      density and dry matter intake (DMI) of that diet by heifers. These diluting
      agents are often sortable by dairy heifers, but previous visual evidence has
      suggested that eastern gamagrass haylage may be a nonsortable alternative. Our
      objectives were (1) to compare the growth performance of dairy heifers offered a
      high-quality forage diet (control) with diets containing 1 of 3 diluting agents
      [eastern gamagrass haylage (EGH), chopped wheat straw (WS), or chopped corn
      fodder (CF)]; and (2) evaluate sorting behaviors of heifers offered these forage
      diets. Holstein heifers (n=128) were stratified (32 heifers/block) on the basis
      of initial body weight (heavy, 560 +/- 27.7 kg; medium-heavy, 481 +/- 17.7 kg;
      medium-light, 441 +/- 22.0 kg; and light, 399 +/- 14.4 kg), and then assigned to
      1 of 16 identical research pens (4 pens/block; 8 heifers/pen), where each of the
      4 research diets were assigned to 1 pen within each block. Diets were offered in
      a 118-d feeding trial with heifers crowded to 133% of capacity at the feed bunk.
      Inclusion of low-energy forages was effective in reducing both diet energy
      density and DMI. Concentrations of physically effective fiber (pef) particles did
      not change during the 24-h period following feeding for either the control or EGH
      diets; however, this response for pef particles masked the competing (and
      cancelling) responses for individual large and medium particles, which heifers
      sorted with discrimination and preference, respectively. Sorting against pef
      particles was detected for WS, and much more severely for the CF diet. Sorting of
      forage particles by heifers could not be related to heifer performance. Compared
      with control (1.16 kg/d), average daily gains (ADG) were reduced by dilution in
      all cases, but were virtually identical between EGH (0.98 kg/d) and CF (0.97
      kg/d), which exhibited no sorting and extensive sorting of pef, respectively.
      Furthermore, ADG for WS was approximately 0.2 kg/d less than EGH or CF, despite
      exhibiting sorting characteristics intermediate between EGH and CF. Diets diluted
      with low-energy forages were formulated to be isonitrogenous and isocaloric;
      within that context, WS was most effective in reducing DMI and maintaining ADG
      within typical recommendations for Holstein heifers.

PMID- 26298763
TI  - Herd management and social variables associated with bulk tank somatic cell count
      in dairy herds in the eastern United States.
AB  - The ability to reduce somatic cell counts (SCC) and improve milk quality depends
      on the effective and consistent application of established mastitis control
      practices. The US dairy industry continues to rely more on nonfamily labor to
      perform critical tasks to maintain milk quality. Thus, it is important to
      understand dairy producer attitudes and beliefs relative to management practices,
      as well as employee performance, to advance milk quality within the changing
      structure of the dairy industry. To assess the adoption rate of mastitis control
      practices in United States dairy herds, as well as assess social variables,
      including attitudes toward employees relative to mastitis control, a survey was
      sent to 1,700 dairy farms in Michigan, Pennsylvania, and Florida in January and
      February of 2013. The survey included questions related to 7 major areas:
      sociodemographics and farm characteristics, milking proficiency, milking systems,
      cow environment, infected cow monitoring and treatment, farm labor, and attitudes
      toward mastitis and related antimicrobial use. The overall response rate was 41%
      (21% in Florida, 39% in Michigan, and 45% in Pennsylvania). Herd size ranged from
      9 to 5,800 cows. Self-reported 3-mo geometric mean bulk tank SCC (BTSCC) for all
      states was 194,000 cells/mL. Multivariate analysis determined that proven
      mastitis control practices such as the use of internal teat sealants and blanket
      dry cow therapy, and not using water during udder preparation before milking,
      were associated with lower BTSCC. Additionally, farmer and manager beliefs and
      attitudes, including the perception of mastitis problems and the threshold of
      concern if BTSCC is above 300,000 cells/mL, were associated with BTSCC. Ensuring
      strict compliance with milking protocols, giving employees a financial or other
      penalty if BTSCC increased, and a perceived importance of reducing labor costs
      were negatively associated with BTSCC in farms with nonfamily employees. These
      findings highlight the need for a comprehensive approach to managing mastitis,
      one that includes the human dimensions of management to maintain the practice of
      scientifically validated mastitis control practices.

PMID- 26298764
TI  - Effect of diet fermentability and unsaturated fatty acid concentration on
      recovery from diet-induced milk fat depression.
AB  - Diet-induced milk fat depression is caused by highly fermentable and high
      unsaturated fatty acid (FA) diets, and results in reduced milk fat concentration
      and yield, reduced de novo FA, and increased trans isomers of the alternate
      biohydrogenation pathways. The hypothesis of the current experiment was that a
      diet higher in fermentability and lower in unsaturated FA (UFA) would accelerate
      recovery compared with a high-UFA and lower-fermentability diet. Eight ruminally
      cannulated and 9 noncannulated multiparous Holstein cows were randomly assigned
      to treatment sequences in a replicated Latin square design. During each period
      milk fat depression was induced for 10 d by feeding a low-fiber, high-UFA diet
      [25.9% neutral detergent fiber (NDF) and 3.3% C18:2]. Following the induction
      phase, cows were switched to recovery treatments for 18 d designed to correct
      dietary fermentability, UFA, or both fermentability and UFA concentration.
      Treatments during recovery were (1) correction of fiber and UFA diet [control;
      31.8% NDF and 1.65% C18:2], (2) a diet predominantly correcting fiber, but not
      UFA [high oil (HO); 31.3% NDF and 2.99% C18:2], and (3) a diet predominantly
      correcting UFA, but not fiber concentration [low fiber (LF); 28.4% NDF and 1.71%
      C18:2]. Milk and milk component yield, milk FA profile, ruminal pH, and 11 rumen
      microbial taxa were measured every third day during recovery. Milk yield
      decreased progressively in HO and control, whereas it was maintained in the LF
      diet. Milk fat concentration increased progressively during recovery in all
      treatments, but was on average 9% lower in LF than control from d 12 to 18. Milk
      fat yield increased progressively in all treatments and was not different between
      control and LF at any time point, but was lower in HO than control on d 15. Milk
      trans-10 C18:1 and trans-10,cis-12 conjugated linoleic acid decreased
      progressively in all treatments, but was higher in HO than control from d 3 to 18
      [136 +/- 50 and 188 +/- 57% (mean +/- SD)], whereas LF caused a smaller increase
      in these FA compared with control (67 +/- 25 and 90 +/- 22%). Additionally, milk
      trans-11 C18:1 and cis-9,trans-11 conjugated linoleic acid was decreased in
      control and LF and increased in HO during recovery. Selected microbial species
      observed changed during recovery, but major treatment differences were only
      observed for Streptococcus bovis. The LF diet that was similar in UFA but 3.4%
      units lower in NDF compared with to the control had a similar decrease in
      alternate trans biohydrogenation intermediates in milk. The HO diet that was
      similar in NDF but 2.0% units higher in UFA compared with the control had higher
      alternate trans biohydrogenation intermediates in milk compared with control.
      However, recovery of milk fat yield was similar between treatments at most time
      points.

PMID- 26298765
TI  - Effect of ceramic membrane channel geometry and uniform transmembrane pressure on
      limiting flux and serum protein removal during skim milk microfiltration.
AB  - Our objectives were to determine the effects of a ceramic microfiltration (MF)
      membrane's retentate flow channel geometry (round or diamond-shaped) and uniform
      transmembrane pressure (UTP) on limiting flux (LF) and serum protein (SP) removal
      during skim milk MF at a temperature of 50 degrees C, a retentate protein
      concentration of 8.5%, and an average cross-flow velocity of 7 m.s(-1).
      Performance of membranes with round and diamond flow channels was compared in UTP
      mode. Performance of the membrane with round flow channels was compared with and
      without UTP. Using UTP with round flow channel MF membranes increased the LF by
      5% when compared with not using UTP, but SP removal was not affected by the use
      of UTP. Using membranes with round channels instead of diamond-shaped channels in
      UTP mode increased the LF by 24%. This increase was associated with a 25%
      increase in Reynolds number and can be explained by lower shear at the vertices
      of the diamond-shaped channel's surface. The SP removal factor of the diamond
      channel system was higher than the SP removal factor of the round channel system
      below the LF. However, the diamond channel system passed more casein into the MF
      permeate than the round channel system. Because only one batch of each membrane
      was tested in our study, it was not possible to determine if the differences in
      protein rejection between channel geometries were due to the membrane design or
      random manufacturing variation. Despite the lower LF of the diamond channel
      system, the 47% increase in membrane module surface area of the diamond channel
      system produced a modular permeate removal rate that was at least 19% higher than
      the round channel system. Consequently, using diamond channel membranes instead
      of round channel membranes could reduce some of the costs associated with ceramic
      MF of skim milk if fewer membrane modules could be used to attain the required
      membrane area.

PMID- 26298766
TI  - Effects of ruminal dosing of Holstein cows with Megasphaera elsdenii on milk fat
      production, ruminal chemistry, and bacterial strain persistence.
AB  - Megasphaera elsdenii is a lactate-utilizing bacterium whose ruminal abundance has
      been shown to be greatly elevated during milk fat depression (MFD). To further
      examine this association, a total of 23 cannulated multiparous Holstein cows were
      examined in 3 experiments in which strains of M. elsdenii were directly dosed
      into the rumen (~2 * 10(12) cells/dose); control cows were dosed with sterile
      lactate-free culture medium. Cows were fed a total mixed ration (292 g of
      starch/kg of dry matter) that contained primarily corn silage, alfalfa silage,
      finely ground high-moisture corn, supplemental protein, and corn oil (3 g/kg of
      dry matter). Experiments differed in stage of lactation of the cows (early or
      late), dosing events (single dose, or 4 doses over a 5-d period), timing of dose
      (prefeed or 4 h postfeed), and M. elsdenii strain (laboratory strain YI9 or 3
      strains isolated from cows in the same herd). Dry matter intake and milk yield
      and composition were measured from 5 to 0 d before dosing and 1 to 7d after first
      dosing, plus later time points that varied by experiment. Milk yield and
      composition were not affected by dosing. Megasphaera elsdenii was quantified in
      the liquid phase of ruminal contents by automated ribosomal intergenic spacer
      analysis, or by PCR with relative quantification (M. elsdenii 16S rRNA gene copy
      number as a percentage of total bacterial 16S rRNA gene copies). Neither the M.
      elsdenii-dosed or control cows displayed MFD after dosing, and in almost all
      cases M. elsdenii populations returned to low baseline levels (<0.02% of 16S rRNA
      gene copy number) within 24 h of dosing. This rapid decline in M. elsdenii also
      occurred in several cows that were dosed with a strain of M. elsdenii that had
      been isolated from that particular cow during a previous bout of MFD. Ruminal pH
      and total millimolar volatile fatty acids and lactate did not differ between
      dosed and control cows, although acetate-to-propionate ratio declined in both
      groups and butyrate increased after dosing with M. elsdenii. The results confirm
      that establishing exogenously added bacterial strains in the rumen is difficult,
      even for strains previously isolated from the recipient cow. The potential role
      of M. elsdenii as an agent of MFD remains unclear in the absence of successful
      establishment of the dosed strains.

PMID- 26298767
TI  - Synchronized ovulation for first insemination improves reproductive performance
      and reduces cost per pregnancy in dairy heifers.
AB  - The objectives were to evaluate the effects of synchronizing estrus and ovulation
      to implement a timed artificial insemination (AI) at first insemination on
      reproductive performance and cost per pregnancy in dairy heifers. Six hundred
      eleven Holsteins heifers at approximately 400 d of age from 3 farms were enrolled
      in the study. Six days before moving to the breeding pens, heifers were allocated
      randomly to AI after detected estrus from study d 0 to 84 (CON, n=306), or to
      timed AI for first AI followed by detected estrus for the remainder of the 84-d
      study (TAI, n=305). Heifers receiving TAI were enrolled in the 5-d timed AI
      protocol on study d -6 (d -6, GnRH and a progesterone insert; d -1, PGF2alpha and
      insert removal; d 0, PGF2alpha; d 2, GnRH + AI), and they were allowed to be bred
      the day before scheduled timed AI if detected in estrus. Starting on study d 0,
      estrus was detected daily. Heifers in estrus were inseminated on the same morning
      as detected estrus. Control heifers not inseminated by study d 7 received
      PGF2alpha and this treatment was repeated every 2 wk until AI. The study lasted
      84 d to allow a period of breeding equivalent to four 21-d estrous cycles. A herd
      budget accounting for inputs for both treatments was created to determine the
      cost per pregnancy. Sensitivity analysis compared economic differences between
      the 2 treatments under different input scenarios when detection of estrus after
      the first AI varied from 50 to 80%. Interval to first AI was 8 d shorter for TAI
      than for CON. Pregnancy at first AI did not differ between treatments (CON=58.3
      vs. TAI=62.8%). In contrast, TAI increased pregnancy per AI (P/AI) compared with
      CON in heifers inseminated with sex-sorted semen (CON=31.6 vs. TAI=54.8%). The 21
      d cycle insemination rate was greater for TAI (91.4%) than for CON (82.4%), even
      when evaluated after the first 21 d in the study (CON=68.2 vs. TAI=77.1%). The
      increased insemination rate improved the 21-d cycle pregnancy rate from 47.9% in
      CON to 57.2% in TAI heifers. In fact, the hazard of pregnancy was 60% greater for
      TAI than CON. The increased pregnancy rate in TAI reduced the median days to
      pregnancy by 12 d (CON=2.0 vs. TAI=14.0) and increased the proportion of pregnant
      heifers by 6.3 percentage points by study d 84 (CON=85.2 vs. TAI=91.5%). The cost
      per pregnancy was $17.00 less for TAI than CON. The sensitivity analysis
      indicated that TAI was economically more advantageous to produce a pregnancy
      compared with CON. Only when insemination rate after the first 21 d of breeding
      was very high and P/AI was relatively low did the cost per pregnancy become
      similar for the 2 treatments. Collectively, inseminating all heifers within 2 d
      of breeding with the 5-d timed AI protocol maintains P/AI, improves pregnancy
      rate, and reduces cost per pregnancy compared with insemination after detected
      estrus. 

PMID- 26298768
TI  - Ex-vivo Donor Heart Perfusion: Testing the Limits of Cardiac Resilience.

PMID- 26298769
TI  - Lipoxin A4 and Neutrophil/Lymphocyte Ratio: A Possible Indicator in Achieved
      Systemic Risk Factors for Periodontitis.
AB  - BACKGROUND: The aim of this study was to evaluate the serum lipoxin A4 (LXA4) and
      neutrophil/lymphocyte (Ne/Ly) ratio in individuals with achieved systemic risk
      factors for periodontitis. MATERIAL AND METHODS: One hundred and eighty
      volunteers (69 male, 111 female) who were categorized as systemically healthy
      control, diabetes, hyperlipidemia, obese and menopause were recruited for this
      cross-sectional study. Sociodemographic characteristics and oral health behaviors
      were recorded via questionnaire. Clinical periodontal parameters, including
      plaque index (PI), gingival index (GI), probing pocket depth (PD), clinical
      attachment level (CAL), sulcus bleeding index (SBI) and decayed, missing, and
      filled teeth index (DMFT), were assessed. Systemic parameters and LXA4 levels
      were evaluated in serum samples. RESULTS: Clinical periodontal parameters and
      DMFT were higher in subjects with achieved systemic risk factors than in healthy
      subjects. The systemically healthy with periodontitis group had higher serum LXA4
      levels than the systemically healthy with non-periodontitis group (P<0.05). The
      Ne/Ly ratio was higher in the hyperlipidemic group with periodontitis than in the
      hyperlipidemic group with non-periodontitis (P<0.05). In the control group, serum
      LXA4 levels were positively correlated with the PD, CAL and SBI. CONCLUSIONS: In
      the presence of periodontitis, an increase in LXA4 levels and the Ne/Ly ratio in
      hyperlipidemic patients could contribute to the hypothesis that these parameters
      could be an indicator in periodontitis and its systemic risk factors.

PMID- 26298770
TI  - New neurons in the adult striatum: from rodents to humans.
AB  - Most neurons are generated during development and are not replaced during
      adulthood, even if they are lost to injury or disease. However, it is firmly
      established that new neurons are generated in the dentate gyrus of the
      hippocampus of almost all adult mammals, including humans. Nevertheless, many
      questions remain regarding adult neurogenesis in other brain regions and
      particularly in humans, where standard birth-dating methods are not generally
      feasible. Exciting recent evidence indicates that calretinin-expressing
      interneurons are added to the adult human striatum at a substantial rate. The
      role of new neurons is unknown, but studies in rodents will be able to further
      elucidate their identity and origin and then we may begin to understand their
      regulation and function. 

PMID- 26298771
TI  - Association between TERT promoter polymorphisms and acute myeloid leukemia risk
      and prognosis.
AB  - Telomerase reverse transcriptase gene (TERT) promoter mutations are identified in
      many malignancies but not in hematological malignancies. Here we analyzed TERT
      and protection of telomeres 1 gene (POT1) mutations, and four different TERT SNVs
      in 226 acute myeloid leukemia (AML) patients and 806 healthy individuals in a
      case referent design, where also overall survival was assessed. A significant
      association for increased risk of AML was found for TERT SNVs, rs2853669 (OR =
      2.45, p = 0.00015) and rs2736100 (OR = 1.5, p = 0.03). The overall survival for
      patients with CC genotype of rs2853669 was significantly shorter compared to
      those with TT or TC genotypes (p = 0.036 and 0.029 respectively). The influence
      of TERT rs2853669 CC on survival was confirmed in multivariable Cox regression
      analysis as an independent risk biomarker in addition to high risk group, higher
      age and treatment. No hot spot TERT promoter mutations at -228C > T or -250C > T
      or POT1 mutations could be identified in this AML cohort. We show that rs2853669
      CC may be a risk factor for the development of AML that may also be used as a
      prognostic marker to identify high risk normal karyotype-AML (NK-AML) patients,
      for treatment guidance. 

PMID- 26298772
TI  - A novel anti-GD2/4-1BB chimeric antigen receptor triggers neuroblastoma cell
      killing.
AB  - Chimeric antigen receptor (CAR)-expressing T cells are a promising therapeutic
      option for patients with cancer. We developed a new CAR directed against the
      disialoganglioside GD2, a surface molecule expressed in neuroblastoma and in
      other neuroectoderm-derived neoplasms. The anti-GD2 single-chain variable
      fragment (scFv) derived from a murine antibody of IgM class was linked, via a
      human CD8alpha hinge-transmembrane domain, to the signaling domains of the
      costimulatory molecules 4-1BB (CD137) and CD3-zeta. The receptor was expressed in
      T lymphocytes by retroviral transduction and anti-tumor activities were assessed
      by targeting GD2-positive neuroblastoma cells using in vitro cytotoxicity assays
      and a xenograft model. Transduced T cells expressed high levels of anti-GD2 CAR
      and exerted a robust and specific anti-tumor activity in 4- and 48-hour cultures
      with neuroblastoma cells. Cytotoxicity was associated with the release of pro
      apoptotic molecules such as TRAIL and IFN-gamma. These results were confirmed in
      a xenograft model, where anti-GD2 CAR T cells infiltrating tumors and persisting
      into blood circulation induced massive apoptosis of neuroblastoma cells and
      completely abrogated tumor growth. This anti-GD2 CAR represents a powerful new
      tool to redirect T cells against GD2. The preclinical results of this study
      warrant clinical testing of this approach in neuroblastoma and other GD2-positive
      malignancies. 

PMID- 26298774
TI  - Differential expression and tumorigenic function of neurotensin receptor 1 in
      neuroendocrine tumor cells.
AB  - Neurotensin (NTS), localized predominantly to the small bowel, stimulates the
      growth of a variety of cancers, including neuroendocrine tumors (NETs), mainly
      through its interaction with the high-affinity NTS receptor 1 (NTSR1). Here, we
      observed increased expression of NTSR1 in almost all tested clinical NET samples,
      but not in normal tissues. Through RT-PCR analysis, we found that the expression
      of NTSR1 and NTSR2 was either variable (NTSR1) or absent (NTSR2) in human NET
      cell lines. In contrast, NTSR3 and NTS were expressed in all NET cells. Treatment
      with 5-aza-2'-deoxycytidine, a demethylating agent, increased levels of NTSR1 and
      NTSR2 suggesting that DNA methylation contributes to NTSR1/2 expression patterns,
      which was confirmed by methylation analyses. In addition, we found that knockdown
      of NTSR1 decreased proliferation, expression levels of growth-related proteins,
      and anchorage-independent growth of BON human carcinoid cells. Moreover, stable
      silencing of NTSR1 suppressed BON cell growth, adhesion, migration and invasion.
      Our results show that high expression of NTSR1 is found in clinical NETs and that
      promoter methylation is an important mechanism controlling the differential
      expression of NTSR1 and silencing of NTSR2 in NET cells. Furthermore, knockdown
      of NTSR1 in BON cells suppressed oncogenic functions suggesting that NTSR1
      contributes to NET tumorigenesis. 

PMID- 26298775
TI  - Evaluation of circulating markers of hepatic apoptosis and inflammation in obese
      children with and without obstructive sleep apnea.
AB  - OBJECTIVE: Hepatocyte apoptosis and macrophage activation contribute to the
      disease progression of nonalcoholic fatty liver disease (NAFLD). Obstructive
      sleep apnea (OSA) in obese children is associated with the severity of NAFLD. The
      aim of this study was to evaluate plasma levels of soluble Fas (sFas), soluble
      Fas ligand (sFasL), cytokeratin 18 (CK18) (markers of apoptosis), and soluble
      CD163 (sCD163) (marker of macrophage activation) in obese children with and
      without OSA. METHODS: Consecutive obese children who were evaluated for OSA were
      recruited. The diagnosis of OSA was made using overnight polysomnography (PSG).
      Fasting blood samples were used to determine plasma CK18, sFas, sFasL, and sCD163
      levels using specific sandwich enzyme-linked immunosorbent assay (ELISA).
      RESULTS: Fifty-eight subjects were included in the analysis with a mean age of
      8.9 +/- 3.2 years and a mean body mass index (BMI) z-score of 2.4 +/- 0.49.
      Circulating sFas and sFasL levels were significantly lower in subjects with mild
      and severe OSA compared with those without OSA (p < 0.005 for both). In addition,
      sCD163 levels increased with an increasing severity of OSA (no OSA = 1.6 +/- 0.25
      mg/L, mild OSA = 2.3 +/- 0.45, and severe OSA = 3.0 +/- 0.52; p < 0.001), and
      they correlated with the apnea-hypopnea index (AHI) [rho (95% confidence
      interval, CI) of 0.71 (0.41, 1.00), p-value <0.001]. In six patients with severe
      OSA from whom samples were taken before and after tonsillectomy, the sCD163 level
      decreased significantly after treatment, and there was a trend toward an increase
      in sFasL. CONCLUSION: Markers of apoptosis and macrophage activation are altered
      in obese children with OSA, indicating increased apoptotic and inflammatory
      pressures.

PMID- 26298776
TI  - A prospective study of Willis-Ekbom disease/restless legs syndrome during and
      after pregnancy.
AB  - OBJECTIVES: Willis-Ekbom disease/restless legs syndrome (WED/RLS) is the most
      common sleep-related movement disorder in pregnancy. We designed a prospective
      longitudinal study to investigate the correlates of WED/RLS during and after
      pregnancy. DESIGN: A total of 138 pregnant women with WED/RLS and a control group
      of 251 age-matched pregnant women were enrolled prospectively. A questionnaire
      was administered during a face-to-face interview at first evaluation during
      pregnancy and three months after delivery. RESULTS: Among all women in the first
      trimester, 15.6% were diagnosed with WED/RLS, whereas 32.8% of those in the
      second trimester and 38.8% of those in the third trimester were diagnosed with
      WED/RLS (p = 0.032). In regression analysis, later gestational age [p < 0.001;
      odds ratio (OR) 1.054] and previous history of WED/RLS (p = 0.001; OR 2.795) were
      positively correlated with the presence of WED/RLS, while ferritin levels (p =
      0.001; OR 0.956) were negatively correlated with the presence of WED/RLS.
      Ferritin levels were also negatively correlated with the International RLS Study
      Group severity index (p = 0.041). Forty-eight patients (34.8%) experienced
      WED/RLS symptomatology after delivery. The ferritin levels were lower, and the
      mean number of pregnancies was higher, in women with residual WED/RLS (p =
      0.008). CONCLUSION: Our survey showed that WED/RLS was more common in the second
      and third trimesters. Emergence of WED/RLS during the second trimester was
      strongly associated with residual WED/RLS. Lower ferritin levels were associated
      with both WED/RLS in pregnancy and residual WED/RLS after delivery. A higher
      number of pregnancies were also associated with a greater likelihood of having
      residual WED/RLS after delivery.

PMID- 26298773
TI  - Tonantzitlolone cytotoxicity toward renal cancer cells is PKCtheta- and HSF1
      dependent.
AB  - Elucidating the targets and mechanism of action of natural products is
      strategically important prior to drug development and assessment of potential
      clinical applications. In this report, we elucidated the main targets and
      mechanism of action of the natural product tonantzitlolone (TZL) in clear cell
      renal cell carcinoma (CCRCC). We identified TZL as a dual PKCalpha and PKCtheta
      activator in vitro, although in CCRCC cells its activity was mostly PKCtheta
      dependent. Through activation of PKCtheta, TZL induced an insulin resistant
      phenotype by inhibiting IRS1 and the PI3K/Akt pathway. Simultaneously, TZL
      activated the heat shock factor 1 (HSF1) transcription factor driving glucose
      dependency. Thus, similar to the selective PKCtheta activator englerin A, TZL
      induces a metabolic catastrophe in CCRCC, starving cells of glucose while
      simultaneously increasing their glycolytic dependency. 

PMID- 26298777
TI  - Environment in pediatric wards: light, sound, and temperature.
AB  - The mutual relationship between sleep and disease is well known, becoming more
      relevant whenever the disease leads to hospitalization. We intend to describe
      patterns of environmental factors of some pediatric wards, and to verify if these
      are in line with those recommended. As a secondary aim, we characterize sleep
      quality during hospitalization. METHODS: Five pediatric wards of a tertiary-level
      hospital were included. Light, sound, and temperature were measured and assessed
      through descriptive statistics. The following recommended values were considered:
      maximum light 100 Lux, maximum sound 45 dB, and optimal temperature 20-24 
      degrees C. A questionnaire was prepared to assess children's sleep, and it was
      completed by a caregiver. RESULTS: Light values were within the desirable limits
      for 86% of evaluated time. In all wards, the intensity of sound was much higher
      than desirable, being above 45 dB during 85% of evaluated time. The temperature
      was above 24  degrees C during 78% of total time. Based on 34 answered
      questionnaires (out of 50 distributed), almost half of the respondents believe
      that sleep quality and restlessness are worse at the hospital. Most children
      slept for a longer time at home. Eighteen children awoke more times at the
      hospital, and those awakenings were mostly attributed to noise. CONCLUSIONS: The
      sound and temperature were higher than recommended. The different values between
      these wards may be due to different levels of care, but this shows that there are
      no standard rules on this matter. A worse quality and shorter duration of sleep
      at hospital were reported. Comprehensive studies are necessary to evaluate the
      impact of environmental factors on disease recovery.

PMID- 26298778
TI  - Sleep in obsessive-compulsive disorder: a systematic review and meta-analysis.
AB  - The aim of this study was to determine whether there are differences in sleep
      between people with and without obsessive-compulsive disorder (OCD), and, if so,
      whether such differences are associated with comorbid depressive symptoms or
      other conditioning factors. We conducted a search for articles published until
      March 2013 in PubMed, Web of Knowledge, PsycINFO, Scopus, Trip Database,
      Dissertation Abstracts, and OpenSIGLE. We retrieved 9658 records, which were
      assessed against the inclusion and quality criteria. Six studies were included in
      the review and four were included in the meta-analysis. They were all cross
      sectional studies with medium methodological quality. All studies except one were
      polysomnographic. The total sample of the meta-analysis consisted of 111 patients
      with OCD and 141 controls. The synthesis of results showed differences in sleep
      between people with and without OCD. The presence of comorbid depression was a
      key issue in the amount and type of differences found. Nevertheless, in order to
      support these results, longitudinal studies should be conducted with larger
      sample sizes and different age ranges. 

PMID- 26298779
TI  - Sleep-associated aspects of myofascial pain in the orofacial area among
      Temporomandibular Disorder patients and controls.
AB  - STUDY OBJECTIVES: To assess sleep-associated aspects of temporomandibular
      disorder (TMD) with myofascial pain (MP) in the orofacial area of patients and
      controls. MEASUREMENTS: Three hundred five female patients were screened to find
      44 participants fulfilling the inclusion criteria, 22 suffering from MP and 22 in
      a control group. Sleep quality was assessed by use of the Pittsburgh Sleep
      Quality-Index (PSQI) and a validated German sleep questionnaire (SF-AR). Tooth
      wear was assessed and anterior temporalis muscle activity was measured at home
      for several nights by use of a portable electromyography (EMG) device. RESULTS:
      22 patients (45.0 +/- 13.6 years) and 22 controls (45.2 +/- 9.0 years) were
      recruited. The PSQI sum-score was 7.5 +/- 3.7 for patients and 4.4 +/- 3.0 for
      controls (p = 0.006). The SF-AR showed that 23% of the controls and 14% of the
      patients were "long sleepers". The overall number of episodes in the two groups
      was not significantly different (4.10 +/- 2.65 versus 4.57 +/- 1.99 episodes per
      hour). However, more patients had temporalis muscle activity possibly related to
      SB during all four consecutive nights (p = 0.04). According to the International
      Classification of Sleep Disorders - Third Edition (ICSD-3) criteria, 13.6% of the
      controls and 71.4% of the patients (p < 0.001) showed SB. CONCLUSIONS: Sleep
      associated disturbances, including reduction of sleep quality and greater
      prevalence of SB and facial pain in the morning, occurred significantly more
      often among TMD patients. Additionally, SB fluctuated over the nights especially
      in controls. This should be taken into consideration when the prevalence of SB is
      assessed by use of EMG.

PMID- 26298780
TI  - Functional disconnection of the right anterior insula in obstructive sleep apnea.
AB  - BACKGROUND: The right anterior insula (AIns) is an important node of the salience
      network and serves to switch between two major cognitive-related functional brain
      networks, ie, the central executive network (CEN) and the default mode network
      (DMN), both of which show functional deficits in obstructive sleep apnea (OSA)
      patients. However, the effect of OSA on functional connectivity of the right AIns
      remains uncertain. OBJECTIVE: To determine whether the resting-state functional
      connectivity (rsFC) between the right AIns and the CEN and DMN is disrupted in
      OSA patients, which may be associated with cognitive deficits in this disorder.
      METHODS: Twenty-four male OSA patients and 21 matched healthy controls underwent
      functional MRI examinations and clinical and neuropsychologic assessments. The
      rsFCs between the right AIns and the CEN and DMN were compared between the two
      groups and were correlated with clinical and neuropsychologic assessments.
      RESULTS: Compared with healthy controls, OSA patients showed significantly
      weakened rsFC between the right AIns and the DMN. Moreover, the functional
      disconnection between the right AIns and the medial prefrontal cortex was
      correlated with the severity of the OSA; and the functional disconnection between
      the right AIns and the posterior cingulate cortex was correlated with depressive
      scores and working memory performance. However, there were no significant inter
      group differences in the rsFC between the right AIns and the CEN. CONCLUSIONS:
      These findings suggest that OSA selectively impairs the rsFC between the right
      AIns and the DMN, which may be a candidate substrate for cognitive impairment in
      OSA patients.

PMID- 26298781
TI  - Chronic dopaminergic treatment in restless legs syndrome: does it affect the
      autonomic nervous system?
AB  - OBJECTIVE: The link between the autonomic nervous system and restless legs
      syndrome (RLS) has been recently postulated. Since dopaminergic agents are used
      as first-line treatment for RLS, the purpose of our study is to verify whether
      chronic pramipexole treatment could influence the autonomic control of
      cardiovascular reflexes and heart rate variability (HRV) in RLS during
      wakefulness. METHODS: Consecutive drug naive RLS patients underwent
      polysomnography (PSG), subjective scales, and cardiovascular function tests
      including head-up tilt test (HUTT), Valsalva maneuver, deep breathing, handgrip
      and cold face before and after 3-month pramipexole therapy. HRV analysis was
      performed in the frequency domain using both autoregressive and fast Fourier
      transform algorithms in rest supine condition and during HUTT. RESULTS: Twenty
      RLS patients reported a significant reduction of RLS symptoms after pramipexole
      treatment, while PSG did not show significant improvements except for periodic
      limb movement index. Pramipexole induced a trend to a lower systolic blood
      pressure and a significant higher variation of systolic and diastolic blood
      pressure at HUTT. Cardiovascular responses to the other tests were unchanged. No
      significant differences in HRV spectral analysis between drug naive and treated
      patients were observed. Moreover, the within-group analysis of HRV between
      orthostatic and supine position did not show any significant change in
      sympathetic and parasympathetic components both in the drug naive and pramipexole
      groups. CONCLUSIONS: Chronic pramipexole treatment does not seem to affect
      autonomic balance during wakefulness. Considering that neither PSG data nor
      autonomic parameters are significantly modified by pramipexole, we hypothesize a
      non-dopaminergic autonomic dysfunction in RLS.

PMID- 26298782
TI  - Predicting poor school performance in children suspected for sleep-disordered
      breathing.
AB  - OBJECTIVE: Habitually snoring children are at a greater risk of poor school
      performance (PSP). We investigated the ability of conventional sleep-disordered
      breathing (SDB) measures for predicting PSP in habitually snoring children.
      METHODS: The dataset of Hannover Study on Sleep Apnea in Childhood (HASSAC), a
      large community-based study in primary school children, was retrospectively
      analyzed. All habitual snorers were included. Based on their grades, children
      were grouped into good and poor school performers. SDB measures obtained by a
      parental questionnaire, a home pulse oximetry, and a home polysomnography were
      evaluated for their accuracy in predicting poor school performance by calculating
      receiver operating characteristic curves and area under this curve (AUC). The
      most predictive single factors were identified and entered into a prediction
      model. RESULTS: Of 114 habitual snorers (mean age 9.6 years, 51 boys), 59 had
      PSP. All investigated SDB measures showed low accuracy (ie, AUC <0.8). The
      highest AUC observed was 0.686 for a questionnaire score, 0.565 for an oximetry
      factor, and 0.624 for a polysomnography factor. Of 20 single significant
      predictors for PSP, five were selected for inclusion into a prediction model. The
      model reached an unadjusted AUC of 0.826 and an adjusted AUC of 0.851.
      CONCLUSIONS: Conventional SDB measures obtained with questionnaire, oximetry, or
      polysomnography may not be sufficiently predictive of PSP in children suspected
      for SDB. However, combining factors in a clinical prediction model may improve
      prediction. Results of such a model may be used to assess the risk of developing
      neurocognitive impairment and to decide whether a child suspected for SDB might
      benefit from treatment.

PMID- 26298783
TI  - Academic performance in adolescents with delayed sleep phase.
AB  - BACKGROUND: Delayed sleep phase (DSP) in adolescence has been linked to reduced
      academic performance, but there are few population-based studies examining this
      association using validated sleep measures and objective outcomes. METHODS: The
      youth@hordaland-survey, a large population-based study from Norway conducted in
      2012, surveyed 8347 high-school students aged 16-19 years (54% girls). DSP was
      assessed by self-report sleep measures, and it was operationalized according to
      the International Classification of Sleep Disorders - Second Edition. School
      performance (grade point average, GPA) was obtained from official administrative
      registries, and it was linked individually to health data. RESULTS: DSP was
      associated with increased odds for poor school performance. After adjusting for
      age and gender, DSP was associated with a threefold increased odds of poor GPA
      (lowest quartile) [odds ratio (OR) = 2.95; 95% confidence interval (CI): 2.03
      4.30], and adjustment for sociodemographics and lifestyle factors did not, or
      only slightly, attenuate this association. Adjustment for nonattendance at school
      reduced the association substantially, and in the fully adjusted model, the
      effect of DSP on poor academic performance was reduced to a non-significant
      level. Mediation analyses confirmed both direct and significant indirect effects
      of DSP on school performance based on school absence, daytime sleepiness, and
      sleep duration. CONCLUSION: Poor academic performance may reflect an independent
      effect of underlying circadian disruption, which in part could be mediated by
      school attendance, as well as daytime sleepiness and short sleep duration. This
      suggests that careful assessment of sleep is warranted in addressing educational
      difficulties.

PMID- 26298784
TI  - Sleep-related modification of atrioventricular block: from first-degree to second
      degree, Mobitz type II.

PMID- 26298785
TI  - Sleep-disordered breathing in chronic heart failure: development and validation
      of a clinical screening score.
AB  - AIMS: Sleep-disordered breathing (SDB) is highly prevalent and of adverse
      prognostic significance in patients with chronic heart failure (CHF). Polygraphy
      is used for diagnosing SDB but polygraphy resources fall short of needs. Here,
      our aim was to develop a score for SDB screening in patients with CHF. METHODS
      AND RESULTS: Consecutive patients with stable chronic CHF referred to our CHF
      clinic for a scheduled follow-up evaluation were included prospectively between
      2000 and 2012. SDB was defined as an apnoea-hypopnoea index >= 5/h as assessed by
      routine polygraphy. A screening score was developed as a linear combination of
      factors independently associated with SDB by multivariate logistic regression.
      Calibration and discrimination were evaluated using the Hosmer-Lemeshow (HL) test
      and area under the receiver-operating characteristics curve (AUC), respectively.
      Bootstrapping was performed to assess internal validity. Of 450 included patients
      (mean age, 59.5 +/- 13.7 years), 397 (88%) had SDB. An easy-to-use score was
      based on age (2 points if >=65 years), body mass index (2 points if >=25
      kg/m(2)), New York Heart Association (NYHA) class (2 points if >=3 or 4) and male
      gender (3 points). A score cut-off of 5 was 78.9% sensitive and 61.5% specific
      for SDB. The final model exhibited adequate calibration (pHL >= 0.3) and
      discrimination (AUC, 0.737; 95% confidence interval, 0.663; 0.810). CONCLUSION:
      An easy-to-use clinical score combining age, body mass index, NYHA class, and
      gender may help to identify those CHF patients most likely to have SDB, thereby
      improving the allocation of scarce polygraphy resources and early diagnosis of
      SDB.

PMID- 26298786
TI  - Effect of oral JZP-110 (ADX-N05) treatment on wakefulness and sleepiness in
      adults with narcolepsy.
AB  - BACKGROUND: JZP-110 is a wake-promoting agent with dopaminergic and noradrenergic
      activity. METHODS: This double-blind, crossover study, randomized adults with
      narcolepsy with or without cataplexy (N = 33) to placebo or JZP-110 at 150 mg/day
      (weeks 1 and 3) increased to 300 mg/day (weeks 2 and 4). Patients had to have
      baseline Epworth Sleepiness Scale (ESS) scores >=10 and mean sleep latencies <=10
      min on the Maintenance of Wakefulness Test (MWT). Efficacy end points included
      MWT sleep latency and ESS, and the percentage of patients improved on the
      Clinical Global Impression of Change. RESULTS: Patients were primarily male
      (57.6%) and white (69.7%), with a mean (standard deviation) age of 37.1 (12.4)
      years. At two weeks, the change in the mean MWT sleep latency was 11.8 min longer
      with JZP-110 than with placebo (P = 0.0002); JZP-110 resulted in greater changes
      in sleep latency on each MWT trial (P <0.001). For ESS, JZP-110 was more
      efficacious relative to placebo after 1 (P <0.0001) and two weeks (P = 0.0002);
      final ESS scores were 10.8 with JZP-110 and 15.2 with placebo, changes of -6.7
      and -2.4, respectively. JZP-110 was generally well tolerated; the most common
      adverse events with JZP-110 were nausea (12%), noncardiac chest discomfort
      (9.1%), and headache (9.1%). CONCLUSIONS: The efficacy of JZP-110 for impaired
      wakefulness and excessive sleepiness was observed at 150-300 mg/day and as early
      as one week after initiating treatment (Clinicaltrials.gov identifier
      NCT01485770).

PMID- 26298787
TI  - Working memory impairment and its associated sleep-related respiratory parameters
      in children with obstructive sleep apnea.
AB  - STUDY OBJECTIVE: Working memory deficits in children with obstructive sleep apnea
      (OSA) have been reported in previous studies, but the results were inconclusive.
      This study tried to address this issue by delineating working memory functions
      into executive processes and storage/maintenance components based on Baddeley's
      working memory model. METHODS: Working memory and basic attention tasks were
      administered on 23 OSA children aged 8-12 years and 22 age-, education-, and
      general cognitive functioning-matched controls. Data on overnight
      polysomnographic sleep study and working memory functions were compared between
      the two groups. Associations between respiratory-related parameters and cognitive
      performance were explored in the OSA group. RESULTS: Compared with controls,
      children with OSA had poorer performance on both tasks of basic storage and
      central executive components in the verbal domain of working memory, above and
      beyond basic attention and processing speed impairments; such differences were
      not significant in the visuo-spatial domain. Moreover, correlational analyses and
      hierarchical regression analyses further suggested that obstructive apnea
      hypopnea index (OAHI) and oxygen saturation (SpO2) nadir were associated with
      verbal working memory performance, highlighting the potential pathophysiological
      mechanisms of OSA-induced cognitive deficits. CONCLUSIONS: Verbal working memory
      impairments associated with OSA may compromise children's learning potentials and
      neurocognitive development. Early identification of OSA and assessment of the
      associated neurocognitive deficits are of paramount importance. Reversibility of
      cognitive deficits after treatment would be a critical outcome indicator.

PMID- 26298788
TI  - Chronic sleep difficulties in non-depressed young women: a longitudinal
      population-based investigation.
AB  - OBJECTIVES/BACKGROUND: Young women are at a risk of poor sleep, but the extent to
      which their sleep difficulties remain chronic is not known. Little is also known
      about the frequency of seeking health care for sleep and satisfaction with that
      health care. This longitudinal study investigated these issues over nine years in
      women who reported sleep difficulties over the preceding 12 months.
      PATIENTS/METHODS: Data from the Australian Longitudinal Study on Women's Health
      were analysed (N = 9683). Information on self-reported sleep difficulties, help
      seeking, and health-care satisfaction was obtained from four surveys collected
      from 2000 (aged 22-27 years) to 2009. Generalized estimating equations were
      conducted to calculate odds ratios (OR) for the likelihood of women who reported
      sleep difficulties in 2000 to report sleep difficulties at subsequent surveys.
      RESULTS: The prevalence of self-reported sleep difficulties 'often' was
      consistent at 9.1-10.8%. Women who reported sleep difficulties 'often' in 2000
      had a markedly increased risk of continued sleep difficulties 'often' over the
      subsequent 9 years [2003: OR (95% confidence interval, CI) = 11.07 (8.03-15.27);
      2006: 12.19 (8.08-16.88); 2009: 10.70 (7.57-15.12)]. Of women who reported sleep
      difficulties 'often' in 2000 (N = 981), 45.1% had persistent sleep problems and
      21.1% experienced relapse of symptoms. About one-third of women who reported
      sleep problems 'often' sought help. CONCLUSION: Self-reported frequent sleep
      difficulties in non-depressed young women strongly predicted a continuation of
      this level of sleep difficulty over a decade, even if help is sought. Current
      health practice may not be breaking the ongoing chronicity of sleep difficulties
      in young women.

PMID- 26298789
TI  - Obstructive sleep apnea exacerbates airway inflammation in patients with chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) concomitant with
      obstructive sleep apnea (OSA) is known as overlap syndrome. It has an increased
      rate of hospitalization due to COPD exacerbation which is believed to indicate a
      worsening of the underlying chronic airway inflammation. Therefore, the aim of
      this prospective study was to explore whether OSA exacerbates airway inflammation
      in subjects with COPD by examining the bronchoalveolar lavage (BAL) fluid.
      METHODS: This prospective study included 47 patients with overlap syndrome and 28
      patients with moderate-to-severe stage stable COPD. Twenty-five patients with
      overlap syndrome adhered to the continuous positive airway pressure (CPAP)
      treatment; the remaining patients either refused CPAP treatment or discontinued
      it within two weeks owing to adverse effects or other reasons. BAL fluid was
      collected from all subjects for the evaluation of cell numbers and tumor necrosis
      factor alpha (TNFalpha) and interleukin-8 (IL-8) levels. RESULTS: The BAL fluid
      of patients with overlap syndrome showed a significantly increased proportion of
      neutrophils and higher TNFalpha concentration and IL-8 levels than that of COPD
      patients; however, the serum CRP levels were not significantly different. An
      association was found between the percentage of neutrophils and the TNFalpha
      concentration and IL-8 levels. Moreover, the TNFalpha concentration was
      significantly correlated with the percentage of nighttime spent with oxygen
      saturation less than 90%. After CPAP treatment, airway inflammation was found to
      decrease significantly. CONCLUSIONS: OSA exacerbates airway inflammation in COPD
      patients. CPAP treatment can improve nocturnal hypoxemia and decrease airway
      inflammation.

PMID- 26298790
TI  - Restless legs syndrome does not affect 3-year mortality in hemodialysis patients.
AB  - OBJECTIVE: Uremic restless legs syndrome (RLS) has been related to an enhanced
      mortality of hemodialysis (HD) patients. In the general population studies of
      this association have yielded inconsistent results. The aim of the present study
      was to re-evaluate the relationship of RLS and mortality in HD patients. METHODS:
      We recorded the 3-year mortality in 579 HD patients after assessment for RLS
      symptoms. This population has been previously evaluated for the prevalence of
      RLS, according to the essential criteria of the International RLS Study Group.
      Mortality data were acquired from the national end-stage renal disease registry.
      Survival probability was calculated by the Kaplan-Meier method and analyzed by
      the log-rank test. For multivariate survival analysis, we implemented a Cox
      regression model. RESULTS: During the 3-year follow-up, we documented 118 deaths.
      Mortality was 15.6% in patients with RLS and 22.3% in patients without RLS (p = 
      0.079). According to the Cox regression analysis, there was no significant
      association between RLS and 3-year mortality, either in an age- and gender
      adjusted model (hazard ratio [HR] = 0.772, 95% confidence interval [CI] = 0.488
      1.219, p = 0.267) or in a multivariate adjusted model (HR = 0.667, 95% CI = 0.417
      1.069, p = 0.092). CONCLUSION: Diagnosis of RLS according to the essential
      criteria of the International RLS Study Group does not seem to influence the 3
      year mortality in HD patients. Our findings are in contrast to those in some
      previous reports, and reinforce the need for further studies of RLS and mortality
      in HD.

PMID- 26298791
TI  - Non-rapid eye movement sleep instability in mild cognitive impairment: a pilot
      study.
AB  - OBJECTIVE: Polysomnographic (PSG) studies in mild cognitive impairment (MCI) are
      not conclusive and are limited only to conventional sleep parameters. The aim of
      our study was to evaluate sleep architecture and cyclic alternating pattern (CAP)
      parameters in subjects with MCI, and to assess their eventual correlation with
      cognition. METHODS: Eleven subjects with MCI (mean age 68.5 +/- 7.0 years), 11
      patients with mild probable Alzheimer's disease (AD; mean age 72.7 +/- 5.9
      years), referred to the Outpatient Cognitive Disorders Clinic, and 11 cognitively
      intact healthy elderly individuals (mean age 69.2 +/- 12.6 years) underwent
      ambulatory PSG for the evaluation of nocturnal sleep architecture and CAP
      parameters. RESULTS: Rapid eye movement sleep, CAP rate, and CAP slow components
      (A1 index) were decreased in MCI subjects and to a greater extent in AD patients,
      compared to cognitively intact controls. AD showed also decreased slow wave sleep
      (SWS) relative to healthy elderly individuals. MCI nappers showed decreased
      nocturnal SWS and A1 subtypes compared to non-nappers. Several correlations
      between sleep variables and neuropsychological tests were found. CONCLUSIONS: MCI
      and AD subjects showed a decreased sleep instability correlated with their
      cognitive decline. Such a decrease may be considered as a potential biomarker of
      underlying neurodegeneration.

PMID- 26298792
TI  - Suicidal ideation and insomnia symptoms in subjects with obstructive sleep apnea
      syndrome.
AB  - OBJECTIVE: Insomnia symptoms are prevalent in subjects with obstructive sleep
      apnea syndrome (OSA) and are important risk factors for suicidal ideation (SI).
      However, the significance of SI has not been clearly demonstrated in persons with
      both OSA and insomnia. We aimed to investigate the prevalence of SI and its
      relationship with insomnia symptoms, mood, and other relevant factors. METHODS: A
      total of 117 consecutive subjects with untreated OSA (apnea-hypopnea index >=5/h)
      participated in the study. They completed questionnaires regarding SI ([BDI-II],
      item 9), insomnia symptoms (Insomnia Severity Index [ISI]), depressive mood
      (modified BDI-II [mBDI-II], which excluded items on SI and sleep disturbances),
      dysfunctional beliefs and attitudes about sleep (DBAS), social support, and
      quality of life. RESULTS: The overall prevalence of SI was 20.5% in subjects with
      OSA. A total of 32 subjects (27.4%) reported significant insomnia symptoms (ISI
      >= 15). Higher SI was associated with higher scores on ISI, DBAS, and mBDI-II and
      lower scores on social support and quality of life questionnaires. The severity
      of insomnia was positively correlated with depressive mood. The relationship
      between SI and insomnia severity was insignificant after adjusting for depressive
      symptom severity. CONCLUSION: Patients with OSA may have SI and insomnia
      symptoms. Collinearity was observed between sleep and mood disturbances. Yet, it
      is remarkable to find a significant association between OSA and SI, which are
      additional contributions to insomnia. This study suggests the necessity of
      integrated approaches to SI and related factors for the comprehensive treatment
      of OSA.

PMID- 26298793
TI  - Analysis of functional GLO1 variants in the BTBD9 locus and restless legs
      syndrome.
AB  - BACKGROUND: Restless legs syndrome (RLS) is a common disorder, with several known
      genetic risk factors, yet the actual genetic causes are unclear. METHODS: Whole
      exome sequencing (WES) was performed in seven RLS families, focusing on six known
      genetic loci: MEIS1, BTBD9, PTPRD, MAP2K5/SKOR1, TOX3, and rs6747972. Genotyping
      using specific TaqMan assays was performed in two case-control cohorts (627
      patients and 410 controls), and in a familial cohort (n = 718). RESULTS: WES
      identified two candidate GLO1 variants (within the BTBD9 locus), p.E111A and the
      promoter variant c.-7C>T, both co-segregated with the disease in four families.
      The GLO1 p.E111A variant was associated with RLS in the French-Canadian cohort
      (odds ratio, OR = 1.38, p = 0.02), and demonstrated a similar trend in the US
      cohort (OR = 1.26, p = 0.09, combined analysis OR = 1.28, p = 0.009). However,
      the original genome-wide association study (GWAS) marker, BTBD9 rs9357271, had
      stronger association with RLS (OR = 1.84, p = 0.0003). Conditional haplotype
      analysis, controlling for the effect of the BTBD9 variant rs9357271, demonstrated
      that the association of GLO1 p.E111A turned insignificant (p = 0.54). In the
      familial cohort, the two GLO1 variants were not associated with RLS. Other
      variants in the SKOR1 (p.W200R and p.A672V) and PTPRD (p.R995C, p.Q447E, p.T781A,
      p.Q447E, and c.551-4C > G) genes, did not co-segregate with the disease.
      CONCLUSIONS: The GLO1 variations studied here are not the source of association
      of the BTBD9 locus with RLS. It is likely that the genetic variants affecting RLS
      susceptibility are located in regulatory regions.

PMID- 26298794
TI  - Willis-Ekbom Disease or Restless Legs Syndrome?
AB  - BACKGROUND: Restless Legs Syndrome (RLS) or Willis-Ekbom Disease (WED) is highly
      prevalent, but patients and healthcare providers alike know little about it.
      Furthermore, controversy persists as to the best way of diagnosing this
      nosological entity. OBJECTIVE: To verify whether the term used to refer to this
      disease entity (Restless Legs Syndrome or Willis-Ekbom Disease) affects the
      prevalence of self-diagnosed RLS/WED in a sample of newly graduated physicians.
      METHODS: Newly graduated physicians were asked to self-evaluate for the presence
      of RLS/WED. Briefly, participants were allocated randomly across two groups. One
      was asked to self-assess for RLS, while the other was asked to self-assess for
      WED. The evaluation form given to one group asked 'Do you have Restless Legs
      Syndrome?' whereas the form given to participants in the other group asked 'Do
      you have Willis-Ekbom Disease?'. Both forms also contained the four criteria for
      diagnosing RLS proposed by the International Restless Legs Syndrome Study Group
      (IRLSSG) and instructions for self-diagnosis according to these criteria.
      RESULTS: The study sample comprised 1413 newly graduated physicians. Of the 708
      participants who were given the form that used the term RLS, 87 (12.28%)
      diagnosed themselves with the condition. Conversely, of 705 physicians given the
      form with the term WED, 13 (1.84%) diagnosed themselves with the condition (p
      <0.0001). CONCLUSION: A greater proportion of newly graduated physicians
      diagnosed themselves with RLS/WED when presented with the term Restless Legs
      Syndrome than when presented with the term Willis-Ekbom Disease. This suggests
      that the term Restless Legs Syndrome may not be the most appropriate term to
      denote this nosological entity.

PMID- 26298796
TI  - Parental poverty and occupation as risk factors for pediatric sleep-disordered
      breathing.
AB  - OBJECTIVES/BACKGROUND: Previous studies have found associations between pediatric
      sleep-disordered breathing (SDB) and socioeconomic status (SES), as well as a
      neighborhood-related disadvantage. This study analyzes the association among
      familial SES, parental occupation, and SDB in Swedish offspring. METHODS: A
      nationwide dataset was constructed by linking Swedish census data to hospital
      discharge register data on all first hospitalizations of children and adolescents
      aged 0-18 years during the study period 1997-2007. The outcome was SDB, defined
      as diagnostic codes for obstructive sleep apnea (OSA), adenotonsillar
      hypertrophy, or tonsillar hypertrophy. Familial SES was defined as family income
      and maternal education. The odds ratio (OR) was calculated with a 95% confidence
      interval (CI). RESULTS: 34,933 of three million children had a first hospital
      diagnosis of SDB. The OR was significantly increased in offspring in families
      with a low income (1.79) and maternal education (1.21). Significantly increased
      ORs were found in 14 of 38 maternal (37%) and 13 of 48 paternal (27%)
      occupations, and six of them involved both parents: drivers, welders, and workers
      in mechanics and iron metalware, chemical processing, and manufacture of food and
      glass. A significantly decreased OR was found in 12 (25%) of the paternal
      occupations, e.g., scientists, physicians, teachers, artists, administrators, and
      farmers, as well as in maternal occupations, such as artists and farmers, with
      offspring aged 0-6 years. CONCLUSION: This study indicates that low familial SES
      and parental occupations associated with a low educational level increased,
      whereas academic parental occupations and farmers decreased the risk of SDB in
      offspring.

PMID- 26298795
TI  - Durability of treatment response to zolpidem with three different maintenance
      regimens: a preliminary study.
AB  - BACKGROUND AND AIM: At present, there is no consensus regarding how to medically
      manage chronic insomnia in the long term. The unstated standard of practice is
      for patients to use hypnotics intermittently. The present study aimed to compare
      a partial reinforcement strategy with nightly and intermittent dosing strategies
      for its potential as a maintenance therapy. METHODS: A mixed model was used in
      the study. One between-subjects factor: group (n = 4). One repeated-measures
      factor: time (12 weekly assessments). A total of 74 subjects with chronic
      Insomnia were treated with 10 mg zolpidem for 4 weeks. Treatment respondents were
      randomized to nightly dosing with 10 mg or 5 mg (QHS-10 and QHS-5), intermittent
      dosing with 10 mg (IDS-10 [3-5 days weekly]), or partial reinforcement dosing
      with 10 mg (PRS-10 [nightly pill use with 50% active medication and 50%
      placebos]) for 12 weeks. RESULTS: It was found, in compliant subjects (n = 55),
      that all four strategies evaluated maintained treatment response over time (ie,
      prevented or delayed relapse). For the subjects that remained in remission, the
      subjects in the intermittent dosing group (IDS-10) group exhibited poorer sleep
      continuity. CONCLUSIONS: While best considered a preliminary study, the present
      findings suggest that the partial reinforcement strategy may be a viable means
      toward maintaining treatment gains over time with less active medication.

PMID- 26298798
TI  - Three-Dimensional Printing and Medical Imaging: A Review of the Methods and
      Applications.
AB  - The purpose of this article is to review recent innovations on the process and
      application of 3-dimensional (3D) printed objects from medical imaging data. Data
      for 3D printed medical models can be obtained from computed tomography, magnetic
      resonance imaging, and ultrasound using the Data Imaging and Communications in
      Medicine (DICOM) software. The data images are processed using segmentation and
      mesh generation tools and converted to a standard tessellation language (STL)
      file for printing. 3D printing technologies include stereolithography, selective
      laser sintering, inkjet, and fused-deposition modeling . 3D printed models have
      been used for preoperative planning of complex surgeries, the creation of custom
      prosthesis, and in the education and training of physicians. The application of
      medical imaging and 3D printers has been successful in providing solutions to
      many complex medical problems. As technology advances, its applications continue
      to grow in the future. 

PMID- 26298797
TI  - Polyphenon E, non-futile at neuroprotection in multiple sclerosis but
      unpredictably hepatotoxic: Phase I single group and phase II randomized placebo
      controlled studies.
AB  - OBJECTIVES: Phase I (PhI): assess the safety of Polyphenon E in people with
      multiple sclerosis (MS) and determine the futility of Polyphenon E as a
      neuroprotective agent. Correlate plasma levels of EGCG with neuroprotective
      effects. Phase II (PhII): Further assess safety and confirm the neuroprotective
      effects of Polyphenon E. DESIGN: PhI: single group futility study. PhII: parallel
      group randomized double-blind placebo-controlled study. PARTICIPANTS: Recruitment
      area (both studies): LSU MS Center, New Orleans, LA and general public from
      surrounding areas. Inclusion criteria (both studies): 1) MS per 2005 McDonald
      criteria; 2) relapsing remitting or secondary progressive MS; 3) stable for six
      months prior to enrollment on either no therapy or glatiramer acetate (GA) for
      the PhI study and on either on GA or Interferon beta for the PhII study.
      Exclusion criteria (both studies): 1) complete bone marrow ablation or
      alentuzumab use at any time; 2) mitoxantrone, cyclophosphamide, natalizumab or
      fingolimod use in the prior nine months; 3) liver problems or significant medical
      problems. INTERVENTIONS: PhI: Polyphenon E, a green tea extract containing 50% of
      the antioxidant Epigallocatechin-gallate (EGCG), two capsules twice daily (200mg
      of EGCG per capsule; total daily dose 800mg) for six months. PhII: Polyphenon E
      or matching placebo capsules, same dose for one year. Only the research
      pharmacist knew treatment assignment and she randomized participants (one-to-one,
      stratified by GA or Interferon beta, blocks of 4 or 6). Outcome evaluators did
      not discuss side effects with participants. OUTCOME MEASURES: PhI: 1) adverse
      events (AE); 2) futility: decrease in N-acetyl aspartate (NAA) from baseline to
      six months of 10% or more; 3) association between EGCG plasma levels and change
      in NAA. PhII: 1) AEs; 2) difference in the rate of change of NAA-levels over
      twelve months.We measured NAA using a point resolved magnetic resonance
      spectroscopic imaging sequence (TE30/TR2000) on a 10cm*10cm*1cm volume of
      interest (VOI) located just superior to the lateral ventricles. The field of view
      was 16*16 resulting in 1cm(3) voxels. We quantified NAA and
      creatine/phosphocreatine (Cr) levels using LCModel for post-processing. RESULTS:
      PhI: Ten participants enrolled and completed all assessments with no serious AEs.
      One discontinued therapy due to grade (G) I abnormal liver function tests (LFTs).
      We included all participants in the analysis. NAA adjusted for creatine increased
      by 10% [95% CI(3.4%,16.2%), p<0.01] rejecting the futility endpoint. PhII:
      Thirteen participants enrolled and twelve started treatment. The DSMB stopped the
      study because 5/7 participants on Polyphenon E had abnormal LFTs (G I, and 1G
      III). Median time to onset of abnormal LFTs was 20 weeks [Inter-Quartile Range
      (IQR) (10,23)]. Only two participants completed the six-month visit, so we could
      not analyze the NAA levels. PhI participants took capsules from lot 189I1107
      while 6/7 PhII participants took capsules from a new lot (L0206306). Both lots
      had similar levels of EGCG but differed in the levels of minor catechins. There
      were no significant differences between the lots on participants' median free
      EGCG plasma levels at either 3h or 8h as well as conjugated EGCG levels at 3h
      (all p>0.4, Wilcoxon exact test). Free EGCG levels at 8h correlated with changes
      in NAA adjusted by water content. A 1ng/ml higher EGCG plasma concentration
      correlated with a 0.9% increase in NAA[95% CI(0.5%,1.4%), visit*level interaction
      F=14.4, p<0.001]. However, EGCG plasma concentrations did not correlate with NAA
      adjusted by creatine (1ng/ml higher EGCG was associated with 0.02%,[95% CI(
      0.27%,0.3%) change in NAA, p>0.5]). There was a trend towards an increase in
      creatine levels (referenced to water content) from baseline to exit (1 5%
      increase, [95% CI(-6%,17%), p=0.4]). The free EGCG levels at 8hours correlated
      significantly with change in creatine levels (1ng/ml higher EGCG level at 8h was
      associated with a 1.1% increase in creatine [95% CI(0.6%,1.6%)]). Thus it is
      possible that the discrepancy between the correlation of the EGCG 8h levels with
      NAA changes referenced to water and the 8h EGCG levels with NAA changes
      referenced to creatine was due to a change in creatine among the subjects with
      higher EGCG levels. Conjugated 3h and 8h levels and free 3h levels did not
      correlate with NAA changes (all p >0.5). CONCLUSIONS/CLASSIFICATION OF EVIDENCE:
      Class III evidence: Polyphenon E at a dose of 400mg of EGCG twice a day is not
      futile at increasing brain NAA levels. Class I evidence: some lots of Polyphenon
      E have a high risk of hepatotoxicity. FUNDING: National Center for Complementary
      and Alternative Medicine K23AT004433, National Multiple Sclerosis Society RG4816
      A-1 and National Institute of General Medical Sciences 1 U54 GM104940. Mitsui
      Norin provided Polyphenon E and placebo and their representative reviewed the
      manuscript prior to publication. Mitsui Norin was not involved in other aspects
      of the study. The decision to submit the manuscript remained with the
      investigators. REGISTRATION: NCT00836719 and NCT01451723

PMID- 26298799
TI  - [Ipilimumab-induced colitis: A new challenge for gastroenterologists].
AB  - Many drugs can produce enterocolitis and they should always be included in the
      differential diagnosis of this clinical picture. Entities such as antibiotic
      associated colitis and neutropenic colitis have been known for some time and
      recently a new type of drug-induced colitis has emerged due to monoclonal
      antibodies. Ipimumab is a humanized monoclonal antibody against the CTLA4
      molecule that is involved in the maturation and regulation of T lymphocyte
      activation. This drug causes immune activation and has an immune-mediated
      antitumor effect with excellent results in tumours such as melanoma. However,
      several immune-related adverse effects may occur in different organs. The most
      frequently involved site is the gastrointestinal tract, with adverse effects
      ranging from mild diarrhoea to colitis with systemic involvement, intestinal
      perforation, and even death. Although no similarities have been found in the
      pathogenesis with inflammatory bowel disease, treatments have been used in
      correlation with its autoimmunological profile: anti-TNF alpha corticosteroids
      have shown clinical efficacy in moderate to severe disease. However the use of
      anti-TNF treatment has not been defined and the safety profile is unknown. The
      inclusion of these new therapies in the treatment of several tumours requires
      familiarity with these entities and their management should be approached as a
      new challenge for the gastroenterologist. For that reason, we conducted a review
      of ipilimumab-induced colitis, evaluating essential features of its symptoms,
      diagnosis and treatment. 

PMID- 26298800
TI  - Two-piece zirconia oral implants withstand masticatory loads: An investigation in
      the artificial mouth.
AB  - OBJECTIVE: To evaluate the fracture resistance of two-piece zirconia oral
      implants after long-term thermomechanical cycling in an aqueous environment. Non
      loaded samples and a one-piece implant system served as control groups. METHODS:
      A total of 48 zirconia implants were evaluated: 16 one-piece implants (ATZ; Group
      A) and 32 differently connected two-piece implants (16 screwed, Group B; 16
      bonded, Group C) made of Y-TZP-A (implant+abutment; B) and Y-TZP-A/ATZ
      (implant/abutment; C), respectively. These groups were divided into two subgroups
      composed of 8 samples. The samples of subgroups 1 (A1, B1, C1) were not exposed
      to any cyclic loading, whereas subgroups 2 (A2, B2, C2) were loaded with 10
      million cycles (98 N). Subsequently, all 48 implants were statically loaded to
      fracture. RESULTS: A constant load on distinct lever arms resulted in different
      exerted bending moments during the dynamic loading (A2: 23.4Ncm, B2: 17.9 Ncm,
      C2: 32.3 Ncm). All implants survived the long-term thermomechanical cycling. For
      the static loading the following average bending moments were calculated: A1/A2:
      362/399 Ncm; B1/B2: 398/346 Ncm; C1/C2: 380/252 Ncm. Foregoing dynamic loading
      significantly increased fracture resistance of Group A implants, whereas Group
      B/C implants showed significantly decreased values. Potentially owed to the
      experimental setup in an aqueous environment of 60  degrees C, 5/8 C2 samples
      showed mobility between implant and abutment due to debonding after dynamic
      loading conditions. SIGNIFICANCE: The evaluated ceramic implant systems seem to
      be able to resist physiological chewing forces long-term. Within the limitations
      of the experimental setup, the connecting mechanism of Group C implants might be
      a weak point.

PMID- 26298801
TI  - Mechanical benefits of conservative restoration for dental fissure caries.
AB  - The principle of minimal intervention dentistry (MID) is to limit removal of
      carious tooth tissue while maximizing its repair and survival potential. The
      objective of this study is to explore the fracture resistance of a permanent
      molar tooth with a fissure carious lesion along with three clinical restoration
      procedures, namely one traditional and two conservative approaches, based upon
      MID. The traditional restoration employs extensive surgical removal of enamel and
      dentine about the cavity to eliminate potential risk of further caries
      development, while conservative method #1 removes significantly less enamel and
      infected dentine, and conservative method #2 only restores the overhanging enamel
      above the cavity and leaves the infected and affected dentine as it was. An
      extended finite element method (XFEM) is adopted here to analyze the fracture
      behaviors of both two-dimensional (2D) and three-dimensional (3D) modeling of
      these four different scenarios. It was found that the two conservative methods
      exhibited better fracture resistance than the traditional restorative method.
      Although conservative method #2 has less fracture resistance than method #1, it
      had significantly superior fracture resistance compared to other restorations.
      More important, after cavity sealing it may potentially enhance the opportunity
      for remineralization and improved loading bearing capacity and fracture
      resistance. 

PMID- 26298802
TI  - Mild Cognitive Impairment, Slow Gait, and Risk of Disability: A Prospective
      Study.
AB  - OBJECTIVES: Mild cognitive impairment (MCI) may be a risk for disability, and co
      occurrence of slow gait (SG) and MCI may increase this risk. DESIGN: Prospective
      study. SETTING: General community. PARTICIPANTS: The study included 3482 older
      adults (mean age: 71.4 years) without disability at baseline. MEASUREMENTS: We
      collected information on demographic variables, measured gait speed and cognitive
      function to diagnose MCI at baseline. During the follow-up period, the incident
      disability was monitored. Participants were divided into groups without MCI and
      SG (control), with SG without MCI (SG), without SG and with MCI in single (sMCI)
      or multiple (mMCI) domains, and with SG and MCI in single (sMCI + SG) and
      multiple (mMCI + SG) domains. RESULTS: During follow-up, 134 participants
      developed disability (mean follow-up: 29.4 months). The proportions of incident
      disability were higher in the MCI with SG, MCI, and SG groups, compared with the
      control group. SG [hazard ratio 2.27 (95% confidence interval: 1.38-3.73)], mMCI
      [2.56 (1.31-5.02)], sMCI + SG [2.46 (1.21-5.00)], and mMCI + SG [3.48 (1.79
      6.76)] participants had risks for disability. CONCLUSIONS: Co-occurrence of SG
      and MCI in multiple domains has a higher risk of disability than each condition
      alone.

PMID- 26298803
TI  - Identification of aberrantly expressed of serum microRNAs in patients with
      hormone-induced non-traumatic osteonecrosis of the femoral head.
AB  - OBJECTIVE: The non-translation RNA-microRNA (miRNA) has been demonstrated to
      correlate to various disease occurrence in body. Serum miRNA was gradually
      considered as molecular markers for disease diagnosis. This study was designed to
      analyze differential serum miRNAs level in hormone-induced non-traumatic
      osteonecrosis of the femoral head (hormone-NOFH) patients. METHODS: We selected
      30 patients with hormone-NOFH as case group, and 30 healthy volunteers were
      recruited as control group. miRCURYTM LNA miRNA chip and quantitative RT-PCR were
      used to examine differential miRNAs expression. Correlation assay was performed
      between miRNAs and NOFH trait. RESULTS: We found that 9 miRNAs were upregulated
      while 3 miRNAs were downregulated in hormone-TOFH patient serum by result of
      miRNA chip. QRT-PCR assay revealed that the level of miR-423-5p was significantly
      increased and miR-10a-5p was significantly decreased. Using Spearman correlation
      analysis, we observed that miR-423-5p serum level is positive association to FHC
      levels whereas miR-10a-5p has no association with FHC levels. Furthermore, miR
      423-5p is negatively correlated to its downstream molecule-adiponectin.
      CONCLUSION: We report a miRNA profile of hormone-NOFH and provide a new
      perspective to understand this intricate disease. This novel information suggests
      the potential roles of miR-423-5p in the diagnosis, prognosis biomarkers, or
      therapy targets of hormone-NOFH.

PMID- 26298804
TI  - Posttraumatic growth in individuals with amputations.
AB  - BACKGROUND: Studying positive outcomes post-amputation is an important area of
      research in order to help individuals recover with the optimal quality of life
      possible. OBJECTIVE: To examine posttraumatic growth (PTG) in the understudied
      population of individuals with amputations. Our main aim was to assess the effect
      of gender, veteran status, age, and time since amputation on PTG. Our secondary
      aim was to examine the role support group participation on PTG. METHODS: Sixty
      six adults with amputations completed an online survey consisting of the
      Posttraumatic Growth Inventory (PTGI) and free response questions about
      experiences with support groups. T-tests and correlations were the main
      statistical analyses. RESULTS: There were no gender differences in PTGI scores.
      Veterans had significantly lower PTGI scores than civilians, t(64) = 2.63, p <
      0.05, Cohen's d = .41. Age was negatively correlated with PTGI score, r = -.27, p
      < 0.05. Participants who indicated consistent engagement in a support group had
      significantly higher PTGI scores than participants without support group
      engagement, t(64) = 3.49, p < 0.01, Cohen's d = .89. CONCLUSIONS: Veterans may be
      a specific population to target for PTG. Support groups appear to be a venue
      associated with higher levels of growth.

PMID- 26298805
TI  - Silicon nanoparticles (SiNp) alleviate chromium (VI) phytotoxicity in Pisum
      sativum (L.) seedlings.
AB  - The present study was aimed to investigate the effect of silicon nanoparticles
      (SiNp) against Cr (VI) phytotoxicity in pea seedlings. Results show that Cr(VI,
      100 MUM) significantly (P < 0.05) declined growth of pea which was accompanied by
      the enhanced level of Cr. Additionally, photosynthetic pigments and chlorophyll
      fluorescence parameters like F(v)/F(m), F(v)/F0 and qP were decreased while NPQ
      significantly (P < 0.05) increased under Cr(VI) treatment. Superoxide radical,
      hydrogen peroxide and malondialdehyde (MDA-lipid peroxidation) contents were
      enhanced by Cr(VI). Activities of antioxidant enzymes like superoxide dismutase
      and ascorbate peroxidase were increased by Cr (VI) while activities of catalase,
      glutathione reductase and dehydroascorbate reductase were inhibited significantly
      (P < 0.05). Micro and macronutrients also show decreasing trends (except S) under
      Cr(VI) treatment. However, addition of SiNp together with Cr(VI) protects pea
      seedlings against Cr(VI) phytotoxicity hence improved growth was noticed. In
      conclusion, the results of this study show that Cr(VI) causes negative impact on
      pea seedlings, however; SiNp protects pea seedlings against Cr(VI) phytotoxicity
      by reducing Cr accumulation and oxidative stress, and up-regulating antioxidant
      defense system and nutrient elements.

PMID- 26298806
TI  - Systemic and local regulation of phosphate and nitrogen transporter genes by
      arbuscular mycorrhizal fungi in roots of winter wheat (Triticum aestivum L.).
AB  - Previous studies have reported that the expression of phosphate (Pi) or nitrogen
      (N) transporter genes in roots of plants could be regulated by arbuscular
      mycorrhizal (AM) fungi, but little is known whether the regulation is systemic or
      not. The present study investigated the systemic and local regulation of multiple
      phosphate and nitrogen transporter genes by four AM fungal species belonging to
      four genera in the roots of winter wheat. A split-root culture system with AM
      inoculated (MR) and non-inoculated root compartments (NR) was used to investigate
      the systemic or local responses of phosphate and nitrogen transporter genes to
      colonization by four AM fungi in the roots of wheat. The expression of four Pi
      transporter, five nitrate transporter, and three ammonium transporter genes was
      quantified using real-time PCR. Of the four AM fungi tested, all locally
      increased expression of the AM-inducible Pi transporter genes, and most locally
      decreased expression of a Pi-starvation inducible Pi transporter gene. The
      addition of N in soil increased the expression of either Pi starvation inducible
      Pi transporters or AM inducible Pi transporters. Inoculation with AM fungi either
      had no effect, or could locally or systemically down-regulate expression of
      nitrogen transporter genes depending on gene type and AM fungal species. 

PMID- 26298807
TI  - Analysis of expression and inhibitory activity of a TrcC-6 phytocystatin present
      in developing and germinating seeds of triticale (*Triticosecale Wittm.).
AB  - Storage proteins of cereal seeds are processed during accumulation and degraded
      during germination primarily by cysteine proteinases. One of the mechanisms
      controlling the activity of these enzymes is the synthesis of specific inhibitors
      named phytocystatins. Here we present the complete gene sequence of a triticale (
      * Triticosecale Wittm.) phytocystatin, TrcC-6, which encodes a 152-amino acid
      protein with a putative 25-amino acid signal peptide. This protein has a
      calculated molecular mass of 16.2 kDa, and was assigned to phylogenetic group B
      of phytocystatins. Because TrcC-6 transcripts are present in triticale seeds, we
      hypothesized that this phytocystatin regulates storage protein accumulation and
      degradation. Therefore, changes in gene expression during the entire period of
      seed development and germination were examined. TrcC-6 transcripts and TrcC-6
      protein levels increased during the maturation of seeds and remained high during
      the first hours of germination. This enabled us to conclude that TrcC-6 likely
      regulates seed germination by the regulation of storage protein hydrolysis. For
      the analysis of TrcC-6 inhibitory activity, recombinant protein was expressed in
      Escherichia coli BL21 (DE3) and purified. Recombinant TrcC-6 proved to be a
      potent inhibitor of cysteine proteinases. It inhibited the in vitro activity of
      papain (EC 3.4.22.2) and ficin (EC 3.4.22.3). Furthermore, native PAGE analysis
      revealed that recombinant TrcC-6 inhibits the activity of endogenous cysteine
      proteinases present in germinating seeds of triticale. Based on these results,
      TrcC-6 is likely one of the important factors that regulate cysteine proteinase
      activity during the accumulation and mobilization of storage proteins.

PMID- 26298809
TI  - Emotional impact of severe post-partum haemorrhage on women and their partners:
      an observational, case-matched, prospective, single-centre pilot study.
AB  - OBJECTIVE: This observational, matched-control, prospective, single-centre study
      sought to estimate the emotional impact of post-partum haemorrhage (PPH) on women
      and their partners, including its influences on post-traumatic stress disorder
      (PTSD), postpartum depression and the mother/child relationship. STUDY DESIGN:
      All consecutive women who were admitted for PPH from December 2010 through
      December 2011 and their partners were screened for eligibility. Emotional impact
      was assessed using three self-reported questionnaires (Impact of Event Scale
      Revised to assess PTSD, Edinburgh Post Natal Depression Scale to assess post
      natal depression and Mother-Infant Bonding Scale to assess the relationship
      between mother and child). Each PPH patient was matched with a control woman for
      whom the delivery was not complicated by PPH. RESULTS: The results showed (a)
      that women with PPH and their partners were more likely to report symptoms
      related to PTSD compared with controls, (b) that women with PPH were less likely
      to suffer from postnatal depression and (c) that there was no difference in the
      mother/child relationship between women with PPH and controls. CONCLUSION: PPH is
      associated with a high incidence of PTSD-related symptoms in both women and their
      partners. PTSD in the context of PPH is likely an under-recognised phenomenon by
      health care professionals.

PMID- 26298808
TI  - Vaginal birth after caesarean section prediction models: a UK comparative
      observational study.
AB  - OBJECTIVE: Primarily, to assess the performance of three statistical models in
      predicting successful vaginal birth in patients attempting a trial of labour
      after one previous lower segment caesarean section (TOLAC). The statistically
      most reliable models were subsequently subjected to validation testing in a local
      antenatal population. STUDY DESIGN: A retrospective observational study was
      performed with study data collected from the Northern Ireland Maternity Service
      Database (NIMATs). The study population included all women that underwent a TOLAC
      (n=385) from 2010 to 2012 in a regional UK obstetric unit. Data was collected
      from the Northern Ireland Maternity Service Database (NIMATs). Area under the
      curve (AUC) and correlation analysis was performed. RESULTS: Of the three
      prediction models evaluated, AUC calculations for the Smith et al., Grobman et
      al. and Troyer and Parisi Models were 0.74, 0.72 and 0.65, respectively. Using
      the Smith et al. model, 52% of women had a low risk of caesarean section (CS)
      (predicted VBAC >72%) and 20% had a high risk of CS (predicted VBAC <60%), of
      whom 20% and 63% had delivery by CS. The fit between observed and predicted
      outcome in this study cohort using the Smith et al. and Grobman et al. models
      were greatest (Chi-square test, p=0.228 and 0.904), validating both within the
      population. CONCLUSION: The Smith et al. and Grobman et al. models could
      potentially be utilized within the UK to provide women with an informed choice
      when deciding on mode of delivery after a previous CS.

PMID- 26298810
TI  - Constructing an atomic-resolution model of human P2X7 receptor followed by
      pharmacophore modeling to identify potential inhibitors.
AB  - The P2X purinoceptor 7 (P2X7R) is a trimeric ATP-activated ion channel gated by
      extracellular ATP. P2X7R has important role in numerous diseases including pain,
      neurodegeneration, and inflammatory diseases such as rheumatoid arthritis and
      osteoarthritis. In this prospective, the discovery of small-molecule inhibitors
      for P2X7R as a novel therapeutic target has received considerable attention in
      recent years. At first, 3D structure of P2X7R was built by using homology
      modeling (HM) and a 50ns molecular dynamics simulation (MDS). Ligand-based
      quantitative pharmacophore modeling methodology of P2X7R antagonists were
      developed based on training set of 49 compounds. The best four-feature
      pharmacophore model, includes two hydrophobic aromatic, one hydrophobic and one
      aromatic ring features, has the highest correlation coefficient (0.874), cost
      difference (368.677), low RMSD (2.876), as well as it shows a high goodness of
      fit and enrichment factor. Consequently, some hit compounds were introduced as
      final candidates by employing virtual screening and molecular docking procedure
      simultaneously. Among these compounds, six potential molecule were identified as
      potential virtual leads which, as such or upon further optimization, can be used
      to design novel P2X7R inhibitors. 

PMID- 26298811
TI  - Computational discovery of novel HIV-1 entry inhibitors based on potent and broad
      neutralizing antibody VRC01.
AB  - Computational prediction of novel HIV-1 entry inhibitors presenting
      peptidomimetics of broadly neutralizing antibody (bNAb) VRC01 was carried out
      based on the analysis of the X-ray complex of this antibody antigen-binding
      fragment with the HIV envelope gp120 core. Using these empirical data,
      peptidomimetic candidates of bNAb VRC01 were identified by a public web-oriented
      virtual screening platform (pepMMsMIMIC) and models of these candidates bound to
      gp120 were generated by molecular docking. At the final point, the stability of
      the complexes of these molecules with gp120 was estimated by molecular dynamics
      and binding free energy calculations. The calculations identified six molecules
      exhibiting a high affinity to the HIV-1 gp120 protein. These molecules were
      selected as the most probable peptidomimetics of bNAb VRC01. In a mechanism
      similar to that of bNAb VRC01, these compounds were predicted to block the
      functionally conserved regions of gp120 critical for the HIV-1 binding to
      cellular receptor CD4. The docked structures of the identified molecules with
      gp120 do not undergo substantial rearrangements during the molecular dynamics
      simulations, in agreement with the low values of free energy of their formation.
      Based on these findings, the selected compounds are considered as promising basic
      structures for the rational design of novel, potent, and broad-spectrum anti-HIV
      1 therapeutics. 

PMID- 26298812
TI  - [C. Jamin in reply to the commentaries by the editorial board of Gynecologie
      Obstetrique & Fertilite on the article entitled: "Emergency contraceptions:
      Propositions of the Orthogenics Commission of the French National College of
      Gynecology and Obstetrics". Gynecol Obstet Fertil 2015;43(9)].

PMID- 26298813
TI  - [Circulating nucleic acids and infertility].
AB  - Circulating nucleic acids (cell-free DNA and microRNAs) have for particularity to
      be easily detectable in the biological fluids of the body. Therefore, they
      constitute biomarkers of interest in female and male infertility care. Indeed, in
      female, they can be used to detect ovarian reserve disorders (polycystic ovary
      syndrome and low functional ovarian reserve) as well as to assess follicular
      microenvironment quality. Moreover, in men, their expression levels can vary in
      case of spermatogenesis abnormalities. Finally, circulating nucleic acids have
      also the ability to predict successfully the quality of in vitro embryo
      development. Their multiple contributions during assisted reproductive technology
      (ART) make of them biomarkers of interest, for the development of new diagnostic
      and/or prognostic tests, applied to our specialty. Circulating nucleic acids
      would so offer the possibility of personalized medical care for infertile couples
      in ART. 

PMID- 26298814
TI  - [Commentaries by the editorial board of Gynecologie Obstetrique & Fertilite on
      the article entitled: "Emergency contraceptions: Propositions of the Orthogenics
      Commission of the French National College of Gynecology and Obstetrics". Gynecol
      Obstet Fertil 2015;43(9)].

PMID- 26298815
TI  - [Emergency contraceptions: Propositions of the Orthogenics Commission of the
      French National College of Gynecology and Obstetrics].

PMID- 26298816
TI  - [Ovarian insufficiency diagnosis in a context of hypogonadotropic hypogonadism].

PMID- 26298818
TI  - A dramatic increase in the positive blood culture rates of Helicobacter cinaedi:
      the evidence of differential detection abilities between the Bactec and
      BacT/Alert systems.
AB  - In our hospital, positive blood culture rates of Helicobacter cinaedi
      dramatically increased after introducing the Bactec system. A simulated culture
      model of H. cinaedi bacteremia demonstrated no positive signals using the
      BacT/Alert system, despite efficient growth in bottles. Clinically suspected H.
      cinaedi bacteremia should be monitored more closely when using the BacT/Alert
      system, preferably with subcultivation after 7days of incubation. 

PMID- 26298817
TI  - Enteropathogenic and enteroaggregative E. coli in stools of children with acute
      gastroenteritis in Davidson County, Tennessee.
AB  - This prospective acute gastroenteritis (AGE) surveillance was conducted in the
      inpatient and emergency room settings at a referral pediatric hospital to
      determine the prevalence of diarrheagenic Escherichia coli (DEC) in children
      <12years of age with AGE in Davidson County, Tennessee. Subjects 15 days to 11
      years of age, who presented with diarrhea and/or vomiting, were enrolled. Stool
      specimens were processed for detection of DEC using multiplex polymerase chain
      reaction. From December 1, 2011, to June 30, 2012, a total of 79 (38%) out of 206
      stool specimens from children with AGE tested positive for E. coli. A total of 12
      (5.8%) out of 206 stool specimens from children with AGE were positive for a DEC.
      Eight (67%) out of these 12 were positive for enteropathogenic E. coli, and the
      remaining 4 were positive for enteroaggregative E. coli. DEC clinical isolates
      clustered with known E. coli enteropathogens according to multilocus sequencing
      typing. 

PMID- 26298819
TI  - Comparison and development of pyrazinamide susceptibility testing methods for
      tuberculosis in Thailand.
AB  - Pyrazinamide (PZA) plays a critical role in shortening tuberculosis treatment
      duration and in treating multi-drug resistant tuberculosis (MDR-TB). The standard
      phenotypic MGIT PZA susceptibility testing method is imperfect because it is slow
      and has potential for false resistance. In this study, we evaluated 2 different
      phenotypic-based methods, quantitative real-time PCR (qPCR) phage assay, and MTT
      assay, as well as genotypic sequencing. The assay was evaluated on 71 clinical
      Mycobacterium tuberculosis isolates (37 MGIT PZA susceptible and 34 MGIT PZA
      resistant) and compared to the MGIT result. Of these methods, the qPCR phage
      assay yielded an accuracy of 89% versus standard MGIT while MTT yielded 83%. The
      genotypic sequencing method yielded 90% accuracy. We conclude that any of these
      faster PZA susceptibility methods perform reasonably well against a MGIT PZA
      susceptibility standard. 

PMID- 26298820
TI  - Actin, actin-related proteins and profilin in diatoms: a comparative genomic
      analysis.
AB  - Diatoms are heterokont unicellular algae with a widespread distribution
      throughout all aquatic habitats. Research on diatoms has advanced significantly
      over the last decade due to available genetic transformation methods and publicly
      available genome databases. Yet up to now, proteins involved in the regulation of
      the cytoskeleton in diatoms are largely unknown. Consequently, this work focuses
      on actin and actin-related proteins (ARPs) encoded in the diatom genomes of
      Thalassiosira pseudonana, Thalassiosira oceanica, Phaeodactylum tricornutum,
      Fragilariopsis cylindrus and Pseudo-nitzschia multiseries. Our comparative
      genomic study revealed that most diatoms possess only a single conventional actin
      and a small set of ARPs. Among these are the highly conserved cytoplasmic Arp1
      protein and the nuclear Arp4 as well as Arp6. Diatom genomes contain genes coding
      for two structurally different homologues of Arp4 that might serve specific
      functions. All diatom species examined here lack ARP2 and ARP3 proteins,
      suggesting that diatoms are not capable of forming the Arp2/3 complex, which is
      essential in most eukaryotes for actin filament branching and plus-end dynamics.
      Interestingly, none of the sequenced representatives of the Bacillariophyta
      phylum code for profilin. Profilin is an essential actin-binding protein
      regulating the monomer actin pool and is involved in filament plus-end dynamics.
      This is the first report of organisms not containing profilin. 

PMID- 26298821
TI  - Long working hours: an avoidable cause of stroke?

PMID- 26298823
TI  - Phase I dose-escalation study of cyclophosphamide combined with bortezomib and
      dexamethasone in Japanese patients with relapsed and/or refractory multiple
      myeloma.
AB  - The present study was conducted to determine the recommended dose (RD) of
      cyclophosphamide (CPM) in the CBD regimen, a triplet combination of CPM,
      bortezomib (BTZ), and dexamethasone (Dex), for relapsed and/or refractory
      multiple myeloma (RRMM). Patients received intravenous CPM on days 1 and 8 at one
      of three dose levels: 300, 400, or 500 mg/m(2), with dose escalation in a 3 + 3
      design. BTZ at 1.3 mg/m(2) was given twice weekly in 3-week cycles, with Dex at
      20 mg/m(2) on the day of and day after BTZ. Of 16 patients enrolled, 15 eligible
      patients were allocated to the study. Dose-limiting toxicities (DLTs) were seen
      in two patients: one in dose level 1 with increased gamma-GTP and the other in
      dose level 3 with increased gamma-GTP and ALT. Both patients spontaneously
      recovered from DLT. Neither therapy-related mortality nor severe adverse events
      were reported during the study. Therefore, the RD of CPM was determined as 500
      mg/m(2). Overall, 2 (13.3 %), 1 (6.7 %), and 8 (53.3 %) patients achieved CR,
      VGPR, and PR, respectively. The regimen was well tolerated and showed promising
      activity in patients with RRMM.

PMID- 26298822
TI  - Long working hours and risk of coronary heart disease and stroke: a systematic
      review and meta-analysis of published and unpublished data for 603,838
      individuals.
AB  - BACKGROUND: Long working hours might increase the risk of cardiovascular disease,
      but prospective evidence is scarce, imprecise, and mostly limited to coronary
      heart disease. We aimed to assess long working hours as a risk factor for
      incident coronary heart disease and stroke. METHODS: We identified published
      studies through a systematic review of PubMed and Embase from inception to Aug
      20, 2014. We obtained unpublished data for 20 cohort studies from the Individual
      Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium and
      open-access data archives. We used cumulative random-effects meta-analysis to
      combine effect estimates from published and unpublished data. FINDINGS: We
      included 25 studies from 24 cohorts in Europe, the USA, and Australia. The meta
      analysis of coronary heart disease comprised data for 603,838 men and women who
      were free from coronary heart disease at baseline; the meta-analysis of stroke
      comprised data for 528,908 men and women who were free from stroke at baseline.
      Follow-up for coronary heart disease was 5.1 million person-years (mean 8.5
      years), in which 4768 events were recorded, and for stroke was 3.8 million person
      years (mean 7.2 years), in which 1722 events were recorded. In cumulative meta
      analysis adjusted for age, sex, and socioeconomic status, compared with standard
      hours (35-40 h per week), working long hours (>=55 h per week) was associated
      with an increase in risk of incident coronary heart disease (relative risk [RR]
      1.13, 95% CI 1.02-1.26; p=0.02) and incident stroke (1.33, 1.11-1.61; p=0.002).
      The excess risk of stroke remained unchanged in analyses that addressed reverse
      causation, multivariable adjustments for other risk factors, and different
      methods of stroke ascertainment (range of RR estimates 1.30-1.42). We recorded a
      dose-response association for stroke, with RR estimates of 1.10 (95% CI 0.94
      1.28; p=0.24) for 41-48 working hours, 1.27 (1.03-1.56; p=0.03) for 49-54 working
      hours, and 1.33 (1.11-1.61; p=0.002) for 55 working hours or more per week
      compared with standard working hours (ptrend<0.0001). INTERPRETATION: Employees
      who work long hours have a higher risk of stroke than those working standard
      hours; the association with coronary heart disease is weaker. These findings
      suggest that more attention should be paid to the management of vascular risk
      factors in individuals who work long hours. FUNDING: Medical Research Council,
      Economic and Social Research Council, European Union New and Emerging Risks in
      Occupational Safety and Health research programme, Finnish Work Environment Fund,
      Swedish Research Council for Working Life and Social Research, German Social
      Accident Insurance, Danish National Research Centre for the Working Environment,
      Academy of Finland, Ministry of Social Affairs and Employment (Netherlands), US
      National Institutes of Health, British Heart Foundation.

PMID- 26298824
TI  - Is repair of the protruded meninges sufficient for treatment of meningocele?
AB  - PURPOSE: The present study aimed to investigate the relationship between
      meningocele and tethered cord syndrome, diagnosis of meningocele associated with
      tethered cord syndrome, and when to perform surgery and the best surgical
      procedure. METHODS: Sixty-nine children with meningocele who were admitted to
      Shanghai Children's Medical Center were analyzed. The relationship between
      meningocele and other lesions causing tethered cord syndrome was studied by
      combining magnetic resonance imaging (MRI) and intraoperative findings. RESULTS:
      The MRI results and intraoperative findings showed that 67 children (97%) had
      associated lesions such as tight filum terminale, fibrous band tethering, spinal
      cord or cauda equina adhesion, diastematomyelia, arachnoid cyst, and epidermoid
      cyst. The protruded meninges were repaired, and the intraspinal lesions were
      treated at the same time. Also, the tethered spinal cord was released. No
      neurological injuries were observed after surgery. CONCLUSIONS: The rate of
      meningocele associated with tethered cord syndrome is very high. MRI is necessary
      for the diagnosis of meningocele. Active surgical treatment is recommended
      immediately after definite diagnosis. During surgery, the surgeon should not only
      repair the protruded meninges but also explore the spinal canal and release the
      tethered cord.

PMID- 26298825
TI  - Diagnostic features of prematurely fused cranial sutures on plain skull X-rays.
AB  - PURPOSE: The characteristic features of prematurely fused craniosynostosis in
      plain radiographs have already been described in literature, but there is no
      clinical trial investigating the individual features of every single form of
      craniosynostosis. We described suture-specific characteristics as well as its
      frequency of appearance in plain radiographs in every different form of
      craniosynostosis. Intraoperative findings served as control to confirm the
      diagnosis. METHODS: One hundred twenty-seven children with prematurely fused
      cranial sutures who underwent a skull X-ray from 2008 to 2012 were investigated
      in the present study. In detail, 34 children with frontal, 60 with sagittal, 13
      with unilateral and 14 with bilateral coronal synostosis and 3 with unilateral
      lambdoid craniosynostosis as well as 3 children with a bilateral lambdoid
      synostosis were included. RESULTS: Typical radiological characteristics in
      craniosynostosis exist. These features as well as its frequency in
      craniosynostosis in plain skull radiographs are presented. In all cases, these
      typical features enabled a correct diagnosis, which was confirmed by
      intraoperative findings. CONCLUSION: The frequency of the appearance of typical
      features is listed and may serve as a "mental internal check list" in the
      radiological approach to craniosynostosis. The study points out the value of
      plain skull X-rays as it enabled proper diagnosis in all investigated 127 cases.

PMID- 26298826
TI  - Drug rash with eosinophilia and systemic symptoms caused by the dietary
      supplement diindolylmethane.

PMID- 26298827
TI  - Time perception impairment in early-to-moderate stages of Huntington's disease is
      related to memory deficits.
AB  - Huntington's disease (HD) primarily affects striatum and prefrontal dopaminergic
      circuits which are fundamental neural correlates of the timekeeping mechanism.
      The few studies on HD mainly investigated motor timing performance in second
      durations. The present work explored time perception in early-to-moderate
      symptomatic HD patients for seconds and milliseconds with the aim to clarify
      which component of the scalar expectancy theory (SET) is mainly responsible for
      HD timing defect. Eleven HD patients were compared to 11 controls employing two
      separate temporal bisection tasks in second and millisecond ranges. Our results
      revealed the same time perception deficits for seconds and milliseconds in HD
      patients. Time perception impairment in early-to-moderate stages of Huntington's
      disease is related to memory deficits. Furthermore, both the non-systematical
      defect of temporal sensitivity and the main impairment of timing performance in
      the extreme value of the psychophysical curves suggested an HD deficit in the
      memory component of the SET. This result was further confirmed by the significant
      correlations between time perception performance and long-term memory test
      scores. Our findings added important preliminary data for both a deeper
      comprehension of HD time-keeping deficits and possible implications on neuro
      rehabilitation practices. 

PMID- 26298828
TI  - A puzzling case without solution: isolated late-onset epileptic seizure.

PMID- 26298829
TI  - The role of white matter dissection technique in modern neuroimaging: can
      neuroradiologists benefit from its use?

PMID- 26298832
TI  - Dose-dependent effects of cannabis on the neural correlates of error monitoring
      in frequent cannabis users.
AB  - Cannabis has been suggested to impair the capacity to recognize discrepancies
      between expected and executed actions. However, there is a lack of conclusive
      evidence regarding the acute impact of cannabis on the neural correlates of error
      monitoring. In order to contribute to the available knowledge, we used a
      randomized, double-blind, between-groups design to investigate the impact of
      administration of a low (5.5 mg THC) or high (22 mg THC) dose of vaporized
      cannabis vs. placebo on the amplitudes of the error-related negativity (ERN) and
      error positivity (Pe) in the context of the Flanker task, in a group of frequent
      cannabis users (required to use cannabis minimally 4 times a week, for at least 2
      years). Subjects in the high dose group (n=18) demonstrated a significantly
      diminished ERN in comparison to the placebo condition (n=19), whereas a reduced
      Pe amplitude was observed in both the high and low dose (n=18) conditions, as
      compared to placebo. The results suggest that a high dose of cannabis may affect
      the neural correlates of both the conscious (late), as well as the initial
      automatic processes involved in error monitoring, while a low dose of cannabis
      might impact only the conscious (late) processing of errors.

PMID- 26298833
TI  - Pharmacological targeting of dopamine D3 receptors: Possible clinical
      applications of selective drugs.
AB  - Dopamine D3 receptors have been pharmacologically engaged in humans since the
      development of the first antipsychotics and ergot-derivative dopamine (DA)
      agonists, even without knowing it. These agents were generally non-selective,
      developed primarily to target D2 receptors. In the last 10 years the
      understanding of the clinical implication of D3 receptors has been progressing
      also due to the identification of D3 gene polymorphisms, the use of more
      selective PET ligands such as [(11)C]-(+)-PHNO and the learning regarding the
      clinical use of the D3-preferential D2/D3 agonists ropinirole and pramipexole. A
      new specific neuroplasticity role of D3 receptor regarding dendrite arborisation
      outgrowth in dopaminergic neurons was also proposed to support, at least in part,
      the slowing of disease observed in subjects with Parkinson's Disease treated with
      DA agonists. Similar mechanisms could be at the basis of the antidepressant-like
      effects observed with DA agonists when co-administered with standard of care.
      Severe adverse event occurring with the use of anti-parkinsonian DA agonists in
      predisposed subjects, i.e., impulse control disorders, are now suggested to be
      putatively related to overactive D3 receptors. Not surprisingly, blockade of D3
      receptors was proposed as treatment for addictive disorders, a goal that could be
      potentially achieved by repositioning buspirone, an anxiolytic drug with D3
      preferential antagonistic features, or with novel selective D3 antagonists or
      partial agonists currently in development for schizophrenia. At the moment ABT
      925 is the only selective D3 antagonist tested in schizophrenic patients in Phase
      II, showing an intriguing cognitive enhancing effects supported by preclinical
      data. Finally, exploratory pharmacogenetic analysis suggested that ABT-925 could
      be effective in a subpopulation of patients with a polymorphism on the D3
      receptor, opening to a possible personalised medicine approach. 

PMID- 26298831
TI  - Brachial plexus 3D reconstruction from MRI with dissection validation: a baseline
      study for clinical applications.
AB  - PURPOSE: The present study aimed to establish a baseline for detailed 3D brachial
      plexus reconstruction from magnetic resonance imaging (MRI). Concretely, the goal
      was to determine the individual brachial plexus anatomy with maximum detail and
      accuracy achievable, as yet irrespective of whether the methods used could be
      economically and practically applied in the clinical setting. MATERIALS AND
      METHODS: Six embalmed cadavers were randomly taken for MRI imaging of the
      brachial plexus. Detailed two-dimensional (2D) segmentation for all brachial
      plexus parts was done. The 2D brachial plexus segmentations were 3D reconstructed
      using Mimics((r)) software. Then, these 3D reconstructions were anatomically
      validated by dissection of the cadavers. After finalising the cadaver
      experiments, brachial plexus MRIs were obtained in three healthy male volunteers
      and the same reconstruction procedure as in vitro was followed. RESULTS: A
      procedure was developed for brachial plexus 3D reconstruction based on MRI
      without the use of any contrast agent. Anatomical validation of six cadaver
      brachial plexus reconstructions showed high correspondence with the dissected
      brachial plexuses. Anatomical variations of the main branches were equally
      present in the 3D reconstructions generated. However, there were also some
      differences that related to the difference between the surface anatomy of the
      nerve and the internal nerve structure. In vivo, it was possible to reconstruct
      the complete brachial plexus in such a manner that normal-appearing BPs were
      derived in a reproducible way. CONCLUSIONS: This study showed that the described
      procedure results in accurate and reproducible brachial plexus 3D
      reconstructions.

PMID- 26298830
TI  - Teaching medical anatomy: what is the role of imaging today?
AB  - PURPOSE: Medical anatomy instruction has been an important issue of debate for
      many years and imaging anatomy has become an increasingly important component in
      the field, the role of which has not yet been clearly defined. The aim of the
      paper was to assess the current deployment of medical imaging in the teaching of
      anatomy by means of a review of the literature. MATERIALS: A systematic search
      was performed using the electronic database PubMed, ScienceDirect and various
      publisher databases, with combinations of the relevant MeSH terms. A manual
      research was added. RESULTS: In most academic curricula, imaging anatomy has been
      integrated as a part of anatomical education, taught using a very wide variety of
      strategies. Considerable variation in the time allocation, content and delivery
      of medical imaging in teaching human anatomy was identified. Given this
      considerable variation, an objective assessment remains quite difficult.
      DISCUSSION: In most publications, students' perceptions regarding anatomical
      courses including imaging anatomy were investigated by means of questionnaires
      and, regardless of the method of teaching, it was globally concluded that imaging
      anatomy enhanced the quality and efficiency of instruction in human anatomy. More
      objective evaluation based on an increase in students' performance on course
      examinations or on specific tests performed before and after teaching sessions
      showed positive results in numerous cases, while mixed results were also
      indicated by other studies. CONCLUSION: A relative standardization could be
      useful in improving the teaching of imaging anatomy, to facilitate its assessment
      and reinforce its effectiveness.

PMID- 26298834
TI  - Association between long-term exposure to air pollution and mortality in France:
      A 25-year follow-up study.
AB  - INTRODUCTION: Long-term exposure to air pollution (AP) has been shown to have an
      impact on mortality in numerous countries, but since 2005 no data exists for
      France. OBJECTIVES: We analyzed the association between long-term exposure to air
      pollution and mortality at the individual level in a large French cohort followed
      from 1989 to 2013. METHODS: The study sample consisted of 20,327 adults working
      at the French national electricity and gas company EDF-GDF. Annual exposure to
      PM10, PM10-2.5, PM2.5, NO2, O3, SO2, and benzene was assessed for the place of
      residence of participants using a chemistry-transport model and taking
      residential history into account. Hazard ratios were estimated using a Cox
      proportional-hazards regression model, adjusted for selected individual and
      contextual risk factors. Hazard ratios were computed for an interquartile range
      (IQR) increase in air pollutant concentrations. RESULTS: The cohort recorded 1967
      non-accidental deaths. Long-term exposures to b aseline PM2.5, PM10-25, NO2 and
      benzene were associated with an increase in non-accidental mortality (Hazard
      Ratio, HR = 1.09; 95% CI: 0.99, 1.20 per 5.9 MUg/m3, PM10-25; HR=1.09; 95% CI:
      1.04, 1.15 per 2.2 MUg/m3, NO2: HR=1.14; 95% CI: 0.99, 1.31 per 19.3 MUg/m3 and
      benzene: HR=1.10; 95% CI: 1.00, 1.22 per 1.7 MUg/m3).The strongest association
      was found for PM10: HR = 1.14; 95% CI: 1.05, 1.25 per 7.8 MUg/m3. PM10, PM10-25
      and SO2 were associated with non-accidental mortality when using time varying
      exposure. No significant associations were observed between air pollution and
      cardiovascular and respiratory mortality. CONCLUSION: Long-term exposure to fine
      particles, nitrogen dioxide, sulfur dioxide and benzene is associated with an
      increased risk of non-accidental mortality in France. Our results strengthen
      existing evidence that outdoor air pollution is a significant environmental risk
      factor for mortality. Due to the limited sample size and the nature of our study
      (occupational), further investigations are needed in France with a larger
      representative population sample.

PMID- 26298835
TI  - Exploring the fate, transport and risk of Perfluorooctane Sulfonate (PFOS) in a
      coastal region of China using a multimedia model.
AB  - Perfluorooctane Sulfonate (PFOS) and related substances have been widely applied
      in both industrial processes and domestic products in China. Exploring the
      environmental fate and transport of PFOS using modeling methods provides an
      important link between emission and multimedia diffusion which forms a vital part
      in the human health risk assessment and chemical management for these substances.
      In this study, the gridded fugacity based BETR model was modified to make it more
      suitable to model transfer processes of PFOS in a coastal region, including
      changes to PFOS partition coefficients to reflect the influence of water salinity
      on its sorption behavior. The fate and transport of PFOS in the Bohai coastal
      region of China were simulated under steady state with the modified version of
      the model. Spatially distributed emissions of PFOS and related substances in 2010
      were estimated and used in these simulations. Four different emission scenarios
      were investigated, in which a range of half-lives for PFOS related substances
      were considered. Concentrations of PFOS in air, vegetation, soil, fresh water,
      fresh water sediment and coastal water were derived from the model under the
      steady-state assumption. The median modeled PFOS concentrations in fresh water,
      fresh water sediment and soil were 7.20ng/L, 0.39ng/g and 0.21ng/g, respectively,
      under Emission Scenario 2 (which assumed all PFOS related substances immediately
      degrade to PFOS) for the whole region, while the maximum concentrations were
      47.10ng/L, 4.98ng/g and 2.49ng/g, respectively. Measured concentration data for
      PFOS in the Bohai coastal region around the year of 2010 were collected from the
      literature. The reliability of the model results was evaluated by comparing the
      range of modeled concentrations with the measured data, which generally matched
      well for the main compartments. Fate and transfer fluxes were derived from the
      model based on the calculated inventory within the compartments, transfer fluxes
      between compartments and advection fluxes between sub-regions. It showed that
      soil and costal water were likely to be the most important sinks of PFOS in the
      Bohai costal region, in which more than 90% of PFOS was stored. Flows of fresh
      water were the driving force for spatial transport of PFOS in this region.
      Influences of the seasonal change of fresh water fluxes on the model results were
      also analyzed. When only seasonal changes of the fresh water flow rates were
      considered, concentrations of PFOS in winter and spring were predicted to be
      higher than that under annual average conditions, while the concentrations in
      summer and autumn were lower. For PFOS fluxes entering the sea, opposite
      conclusions were drawn compared to the concentrations. Environmental risks from
      the presence of PFOS in fresh water were assessed for this region through
      comparison with available water quality criteria values. The predicted
      concentrations of PFOS in the Bohai coastal region provided by the model were
      lower than the water quality criteria published by the United States
      Environmental Protection Agency and Chinese researchers, while the concentrations
      in more than 80% of the sampling locations exceeded the European Union Water
      Framework Directive Environmental Quality Standards values. Seasonal variations
      of flow rate might cause a significant increase in environmental risks. 

PMID- 26298836
TI  - Preferential retrotransposition in aging yeast mother cells is correlated with
      increased genome instability.
AB  - Retrotransposon expression or mobility is increased with age in multiple species
      and could promote genome instability or altered gene expression during aging.
      However, it is unclear whether activation of retrotransposons during aging is an
      indirect result of global changes in chromatin and gene regulation or a result of
      retrotransposon-specific mechanisms. Retromobility of a marked chromosomal Ty1
      retrotransposon in Saccharomyces cerevisiae was elevated in mother cells relative
      to their daughter cells, as determined by magnetic cell sorting of mothers and
      daughters. Retromobility frequencies in aging mother cells were significantly
      higher than those predicted by cell age and the rate of mobility in young
      populations, beginning when mother cells were only several generations old. New
      Ty1 insertions in aging mothers were more strongly correlated with gross
      chromosome rearrangements than in young cells and were more often at non
      preferred target sites. Mother cells were more likely to have high concentrations
      and bright foci of Ty1 Gag-GFP than their daughter cells. Levels of
      extrachromosomal Ty1 cDNA were also significantly higher in aged mother cell
      populations than their daughter cell populations. These observations are
      consistent with a retrotransposon-specific mechanism that causes
      retrotransposition to occur preferentially in yeast mother cells as they begin to
      age, as opposed to activation by phenotypic changes associated with very old age.
      These findings will likely be relevant for understanding retrotransposons and
      aging in many organisms, based on similarities in regulation and consequences of
      retrotransposition in diverse species. 

PMID- 26298837
TI  - Modal variety of microsatellite instability in human endometrial carcinomas.
AB  - PURPOSE: Microsatellite instability (MSI) in human endometrial cancer (EC) was
      analysed using a unique fluorescent technique. MSI is associated with various
      human neoplasms. However, the reported frequency of MSI differs widely in each
      malignancy. Methodological difficulties have in fact been pointed out in its
      assay techniques. METHODS: We previously established a sensitive fluorescent
      technique in which the major methodological problems are overcome. Application of
      this technique has revealed two distinct modes of microsatellite alterations,
      i.e. Type A and Type B. In the present study, we have applied this technique to
      94 ECs. RESULTS: Significant microsatellite alterations were observed in 38
      (40.4%) tumours of the panel. The two modes, Type A and Type B, were indeed
      observed in this malignancy. More importantly, we found that the modes more
      closely correlated with the molecular and clinicopathological backgrounds of the
      tumours than the established and widely used MSI grades, MSI-H and MSI-L. Type B
      MSI widely correlated with family history of hereditary non-polyposis colorectal
      cancer-associated cancers, whereas MSI-H only did with that of colorectal cancer.
      Furthermore, mutation in the KRAS oncogene, which has been regarded as generally
      infrequent in microsatellite-unstable tumours, was clearly associated with Type A
      MSI. CONCLUSIONS: Our observations may suggest a biological relevance and a
      potential utility of the modal classification of MSI and, furthermore, added
      complexities to genomic instability underlying tumourigenesis in human
      endometrium.

PMID- 26298838
TI  - Incidence of metachronous contralateral breast cancer in the Canton of Zurich: a
      population-based study of the cancer registry.
AB  - PURPOSE: To examine the incidence and characteristics of metachronous
      contralateral breast cancer (CBC) among women in the Canton of Zurich,
      Switzerland. METHODS: For 1980-2006, patients with unilateral invasive breast
      cancer (UBC) were analysed for metachronous CBC. Poisson's regression was used to
      estimate incidence rates of metachronous CBC according to age, year of diagnosis,
      follow-up period since first breast cancer and morphology. RESULTS: Of 16,323
      patients with UBC, 700 (4.3%) developed a second malignant tumour of the opposite
      breast. Median age at first breast cancer was lower in the CBC group than in the
      full cohort. Median interval time between first and second breast cancer was 5.5
      (interquartile range 2.6-10.1) years. Incidence rate at age 20-29 was 1006 (95%
      confidence interval, CI, 452-2238) cases per 100,000 person-years and decreased
      to 299 (199-450) at 80-84. Age-adjusted incidence rates according to period of
      diagnosis decreased from 618 (530-721) for 1980-1984 to 329 (217-500) cases per
      100,000 person-years for 2005-2006. Incidence rate ratio of CBC for lobular
      carcinoma was 1.28 (95% CI 0.99-1.67) adjusted by age group and period of
      diagnosis compared to ductal carcinoma. CONCLUSIONS: In our study, incidence
      rates for CBC are comparable with findings from the literature. A reduction in
      the incidence of metachronous CBC, thought to be due to adjuvant therapies, is
      seen in our data. In our cohort, younger age and lobular carcinoma were
      associated with an increased risk of CBC.

PMID- 26298839
TI  - Is Acupuncture Efficacious for Treating Phonotraumatic Vocal Pathologies? A
      Randomized Control Trial.
AB  - OBJECTIVES: To investigate the effectiveness of acupuncture in treating
      phonotraumatic vocal fold lesions. STUDY DESIGN/METHODS: A total of 123 dysphonic
      individuals with benign vocal pathologies were recruited. They were given either
      genuine acupuncture (n = 40), sham acupuncture (n = 44), or no treatment (n = 39)
      for 6 weeks (two 30-minute sessions/wk). The genuine acupuncture group received
      needles puncturing nine voice-related acupoints for 30 minutes, two times a week
      for 6 weeks, whereas the sham acupuncture group received blunted needles
      stimulating the skin surface of the nine acupoints for the same frequency and
      duration. The no-treatment group did not receive any intervention but attended
      just the assessment sessions. One-hundred seventeen subjects completed the study
      (genuine acupuncture = 40; sham acupuncture = 43; and no treatment = 34), but
      only 84 of them had a complete set of vocal functions and quality of life
      measures (genuine acupuncture = 29; sham acupuncture = 33; and no-treatment = 22)
      and 42 of them with a complete set of endoscopic data (genuine acupuncture = 16;
      sham acupuncture = 15; and no treatment = 11). RESULTS: Significant improvement
      in vocal function, as indicated by the maximum fundamental frequency produced,
      and also perceived quality of life, were found in both the genuine and sham
      acupuncture groups, but not in the no-treatment group. Structural (morphological)
      improvements were, however, only noticed in the genuine acupuncture group, which
      demonstrated a significant reduction in the size of the vocal fold lesions.
      CONCLUSIONS: The findings showed that acupuncture of voice-related acupoints
      could bring about improvement in vocal function and healing of vocal fold
      lesions.

PMID- 26298840
TI  - Botulinum Toxin A for Treatment of Contact Granuloma.
AB  - OBJECTIVES: Contact granuloma has been associated with voice abuse,
      laryngopharyngeal reflux, and habitual throat clearing. It has a high propensity
      for persistence and recurrence. Treatment options included voice therapy and
      antireflux measures. Surgical excision has been considered in patients who do not
      respond to medical management. In this research, we aimed to present our
      experience with botulinum toxin injection only. STUDYDESIGN: Retrospective case
      series of a tertiary referral center. METHODS: Our series consisted of 22
      patients, who underwent botulinum toxin injection only as an office procedure to
      bilateral thyroarytenoid and lateral cricoarytenoid muscles in 2 * 1.25 to 2 *
      2.5 U. No other treatment was applied. The cases were followed up for at least 6
      months ranging between 6 and 100 months with a mean of 28. RESULTS: Seventeen
      cases (77%) were cured of their granuloma. Eleven of the cured cases had grade 2,
      four cases had grade 1, and two patients had grade 3 granuloma. CONCLUSIONS:
      Botulinum toxin A injection only is an efficient treatment modality in contact
      granuloma, especially for grade 1, 2, and 3 cases, and it can be used as a first
      line treatment.

PMID- 26298841
TI  - Seeing in the Mind's eye: Imagery rescripting for patients with body dysmorphic
      disorder. A single case series.
AB  - BACKGROUND: Intrusive images of appearance play an important role in the
      maintenance of body dysmorphic disorder (BDD) and are often linked to negative
      autobiographical experiences. However, to date there is no study examining the
      use and efficacy of imagery rescripting in BDD. METHOD: This study investigated
      imagery rescripting in six patients with BDD, using a single case series A-B
      design. The intervention consisted of two treatment sessions (T1, T2). BDD and
      depressive symptoms were evaluated prior to (T1), post (T2) and two weeks after
      intervention (FU), using the Yale -Brown Obsessive Compulsive Scale for BDD (BDD
      YBOCS), the Body Dysmorphic Symptoms Inventory, and the Beck Depression
      Inventory. RESULTS: At post-treatment, significant reductions in negative affect,
      distress, vividness and encapsulated beliefs associated with images and memories
      as well as an increased control were observed for five of six patients. These
      were maintained or decreased at two weeks follow-up. Scores on the BDD-YBOCS
      indicated a significant 26% improvement in BDD severity at follow-up for the
      whole group. Considering response as a >= 30% reduction in BDD-YBOCS score, four
      of six patients were classified as treatment responders. At follow-up,
      significant improvements in BDD and depressive symptoms were observed for the
      whole group. LIMITATIONS: The small sample size and the lack of a control group
      limit the generalizability of our results. CONCLUSIONS: The findings indicate the
      potential efficacy of imagery rescripting, and highlight the need for further
      controlled trials. Imagery rescripting should be considered as a treatment
      technique within the cognitive framework of BDD.

PMID- 26298842
TI  - The effects of a documentary film about schizophrenia on cognitive, affective and
      behavioural aspects of stigmatisation.
AB  - BACKGROUND AND OBJECTIVES: Stereotypes about schizophrenia may lead to
      prejudicial attitudes and discrimination with debilitating effects on people
      diagnosed with schizophrenia. There is thus a need to develop interventions
      aiming to prevent, reduce or eliminate such stereotypes. The aim of this study
      was to evaluate the effects of a documentary film on schizophrenia on cognitive,
      affective and behavioural aspects of stigmatisation. METHODS: Forty-nine
      participants were assessed on measures of stereotypes and social distance, and on
      the Model of Stereotype Content, which includes measures of stereotypes,
      emotional reactions and behavioural tendencies. Participants were randomly
      assigned into either a condition in which they viewed the documentary film (Film
      group), or into a control condition in which no intervention was conducted
      (Control group). RESULTS: Only participants in the Film group revealed a
      significant decrease of negative stereotypes (Dangerousness and Unpredictability)
      and desired Social distance, and a significant increase in the perception of
      sociability in persons with schizophrenia. LIMITATIONS: Small sample size and its
      reduced generalizability are the main limitations in this study. CONCLUSIONS:
      These findings suggest that a documentary film promoting indirect contact with
      people diagnosed with schizophrenia is a promising tool to prevent and reduce
      stigmatisation regarding schizophrenia..

PMID- 26298843
TI  - First empirical evaluation of the link between attachment, social cognition and
      borderline features in adolescents.
AB  - OBJECTIVE: Several developmental models of borderline personality disorder (BPD)
      emphasize the role of disrupted interpersonal relationships or insecure
      attachment. As yet, attachment quality and the mechanisms by which insecure
      attachment relates to borderline features in adolescents have not been
      investigated. In this study, we used a multiple mediational approach to examine
      the cross-sectional interplay between attachment, social cognition (in particular
      hypermentalizing), emotion dysregulation, and borderline features in adolescence,
      controlling for internalizing and externalizing symptoms. METHODS: The sample
      included 259 consecutive admissions to an adolescent inpatient unit (Mage=15.42,
      SD=1.43; 63.1% female). The Child Attachment Interview (CAI) was used to obtain a
      dimensional index of overall coherence of the attachment narrative. An
      experimental task was used to assess hypermentalizing, alongside self-report
      measures of emotion dyregulation and BPD. RESULTS: Our findings suggested that,
      in a multiple mediation model, hypermentalizing and emotion dysregulation
      together mediated the relation between attachment coherence and borderline
      features, but that this effect was driven by hypermentalizing; that is, emotion
      dysregulation failed to mediate the link between attachment coherence and
      borderline features while hypermentalizing demonstrated mediational effects.
      CONCLUSIONS: The study provides the first empirical evidence of well-established
      theoretical approaches to the development of BPD.

PMID- 26298844
TI  - Enlarging an accidental mucosotomy to facilitate tumor extraction during
      submucosal tunneling endoscopic resection for a giant esophageal leiomyoma.

PMID- 26298845
TI  - Sustained low-efficiency extended dialysis (SLED) with single-pass batch system
      in critically-ill patients with acute kidney injury (AKI).
AB  - BACKGROUND: Single-pass batch dialysis (SBD) is a well-established system for
      treatment of end-stage renal disease. However, little evidence is available on
      sustained low-efficiency extended dialysis (SLED) performed with SBD in patients
      with acute kidney injury (AKI) in the intensive care unit (ICU). METHODS: All
      SLED-SBD sessions conducted on AKI patients in nine ICUs between March and June
      2010 were retrospectively analyzed regarding the achieved metabolic and fluid
      control. Logistic regression was performed to identify the risk factors
      associated with hypotension and clotting during the sessions. RESULTS: Data from
      106 patients and 421 sessions were analyzed. Patients were 54.2 +/- 17.0 years
      old, 51 % males, and the main AKI cause was sepsis (68 %); 80 % of patients
      needed mechanical ventilation and 55 % vasoactive drugs. Hospital mortality was
      62 %. The median session time was 360 min [interquartile range (IQR) 300-360] and
      prescribed ultrafiltration was 1500 ml (IQR 800-2000). In 272 sessions (65 %) no
      complications were recorded. No heparin was used in 269/421 procedures (64 %) and
      system clotting occurred in 63 sessions (15 %). Risk factors for clotting were
      sepsis [odds ratio (OR) 2.32 (1.31-4.11), p = 0.004], no anticoagulation [OR 2.94
      (1.47-5.91), p = 0.002] and the prescribed time (hours) [OR 1.14 (1.05-1.24), p =
      0.001]. Hypotension occurred in 25 % of procedures and no independent risk
      factors were identified by logistic regression. Adequate metabolic and fluid
      balance was achieved during SLED sessions. Median blood urea decreased from 107
      to 63 mg/dl (p < 0.001), potassium from 4.1 to 3.9 mEq/l (p < 0.001), and
      increased bicarbonate (from 21.4 to 23.5 mEq/l, p < 0.001). Median fluid balance
      during session days ranged from +1300 to -20 ml/24 h (p < 0.001). CONCLUSIONS:
      SLED-SBD was associated with a low incidence of clotting despite frequent use of
      saline flush, and achieved a satisfactory hemodynamic stability and reasonable
      metabolic and fluid control in critically-ill AKI patients.

PMID- 26298846
TI  - Time-tuning cancer therapy.

PMID- 26298847
TI  - [Drug management of prisoners: Role of the pharmaceutical staff to ensure patient
      safety].
AB  - OBJECTIVES: In the prisons of Lyon, drug management of inmates implies
      cooperation between general practitioners, psychiatrists and pharmacists. All the
      medical prescriptions are reviewed by the pharmacists of the medical unit. The
      aim of this work was to synthesize the pharmaceutical interventions performed and
      show the implication of the pharmaceutical staff in detecting and handling
      prescribing errors. METHODS: Pharmaceutical interventions performed between the
      1st of June 2012 and the 31st December 2014 and entered in the Act-IP((r))
      database (SFPC) were retrospectively analyzed. RESULTS: Among the 18,205
      prescriptions reviewed, 4064 (22.3%) had a prescription error. The main problems
      encountered were by decreasing order of frequency: missing monitoring (15% of the
      interventions), lack of compliance (13%), over dosage (10%), lack of conformity
      with recommendations or consensus (8%). Interventions were accepted in 78% cases.
      Most prescribing errors implied medications of the central nervous system. Among
      the interventions, 8% were initiated by pharmacy technicians, mainly lack of
      compliance. CONCLUSIONS: The pharmaceutical interventions reported reflected
      actions of securisation initiated by the pharmacists in cooperation with
      physicians: monitoring of patients taking antipsychotic medications or
      benzodiazepines maximal dosages. Besides, in this population with a high
      prevalence of psychiatric comorbidities and important suicide rate, detection of
      patients with default of compliance is one of the keys for drug optimization
      among these patients as it is an explanation for therapeutic failure.

PMID- 26298848
TI  - [Medication errors with concentrated potassium intravenous solutions: Data of the
      literature, context and prevention].
AB  - Accidental direct intravenous injection of a concentrated solution of potassium
      often leads to patient death. In France, recommendations of healthcare agencies
      to prevent such accidents cover only preparation and intravenous infusion
      conditions. Accidents continue to occur in French hospitals. These facts
      demonstrate that these recommendations are insufficient and ineffective to
      prevent such deaths, especially those occurring during a catheter flushing. This
      article reviews the measures able to reduce the number of accidents. Countries
      which removed concentrated ampoules from ward stocks observed a decrease of the
      number of accidental deaths. This withdrawal, recommended by the World Health
      Organization, is now part of standards in studies aimed at determining the safety
      of care in hospitals. However, removal alone is insufficient to eliminate the
      risk. The combination with other measures should be considered. These measures
      are the provision of a combination of diluted intravenous ready to use solutions,
      the promotion of the oral route with tablets and oral solutions for potassium
      replenishment and to make available products with safeguards to prevent single
      shot intravenous injection. Studies aimed at determining the consequences on
      preventing concentrated potassium accidents of a widespread distribution of
      isotonic sodium chloride pre-filled ready-to-use syringes for catheter flushing
      should be performed. 

PMID- 26298849
TI  - Susceptibility of pancreatic cancer stem cells to reprogramming.
AB  - Previous reports have indicated that reprogramming technologies may be useful for
      altering the malignant phenotype of cancer cells. Although somatic stem cells in
      normal tissues are more sensitive to reprogramming induction than differentiated
      cells, it remains to be elucidated whether any specific subpopulations are
      sensitive to reprogramming in heterogeneous tumor tissues. Here we examined the
      susceptibility of pancreatic cancer stem cells (CSC) and non-CSC to
      reprogramming. To characterize CSC populations, we focused on c-Met signaling,
      which has been identified as a marker of CSC in mouse experiments in vivo. Cells
      that expressed high levels of c-Met showed higher CSC properties, such as tumor
      initiating capacity, and resistance to gemcitabine. Real-time reverse
      transcription-polymerase chain reaction in cells expressing high levels of c-Met
      revealed endogenous expression of reprogramming factors, such as OCT3/4, SOX2,
      KLF4 and cMYC. Introduction of these four factors resulted in higher alkaline
      phosphatase staining in cells with high c-Met expression than in controls.
      Therefore, the study results demonstrate that cellular reprogramming may be
      useful for extensive epigenetic modification of malignant features of pancreatic
      CSC.

PMID- 26298850
TI  - Benefits and limitations of an intercalibration of phytoplankton assessment
      methods based on the Mediterranean GIG reservoir experience.
AB  - The status of European legislation regarding inland water quality after the
      enactment of the Water Framework Directive (WFD) originated scientific effort to
      develop reliable methods, primarily based on biological parameters. An important
      aspect of the process was to ensure that quality assessment was comparable
      between the different Member States. The Intercalibration process (IC), required
      in the WFD ensures the unbiased application of the norm. The presented results
      were developed in the context of the 2nd IC phase. An overview of the reservoir
      type definition of the Lake Mediterranean Geographical Intercalibration Group,
      where four types were considered divided by both alkalinity and climate, together
      with the results for selection of Maximum Ecological Potential sites (MEP) are
      presented. MEP reservoirs were selected based on pressure and biological
      variables. Three phytoplankton-based assessment methods were intercalibrated
      using data from Mediterranean countries. The Mediterranean Assessment System for
      Reservoirs Phytoplankton (Spain), the New Mediterranean Assessment System for
      Reservoirs Phytoplankton (Portugal and Cyprus) and the New Italian Method (Italy)
      were applied. These three methods were compared through option 3 of the
      Intercalibration Guide. The similarity of the assessments was quantified, and the
      Good/Moderate (GM) boundaries assessed. All three methods stood as comparable at
      the GM boundary except for the MASRP in siliceous wet reservoirs, which was
      slightly stricter. Finally, the main taxonomic groups represented in the
      phytoplankton community at MEP conditions were identified, as well as their main
      changes with an increasing trophic status. MEP sites are dominated by
      chrysophytes in siliceous wet reservoirs and by the diatoms Cyclotella and
      Achnanthes in calcareous ones. Cyanobacteria take over the community in both
      calcareous and siliceous wet reservoirs as eutrophication increases. In summary,
      the relevance and reliability of the quality assessment methods compared were
      confirmed both from an ecological perspective and a health risk management point
      of view. 

PMID- 26298851
TI  - Variations of emission characterization of PAHs emitted from different utility
      boilers of coal-fired power plants and risk assessment related to atmospheric
      PAHs.
AB  - Coal-fired power plants (CFPPs) represent important source of atmospheric PAHs,
      however, their emission characterization are still largely unknown. In this work,
      the concentration, distribution and gas-particle partitioning of PM10- and gas
      phase PAHs in flue gas emitted from different coal-fired utility boilers were
      investigated. Moreover, concentration and distribution in airborne PAHs from
      different functional areas of power plants were studied. People's inhalatory and
      dermal exposures to airborne PAHs at these sites were estimated and their
      resultant lung cancer and skin cancer risks were assessed. Results indicated that
      the boiler capacity and operation conditions have significant effect on PAH
      concentrations in both PM10 and gas phases due to the variation of combustion
      efficiency, whereas they take neglected effect on PAH distributions. The wet flue
      gas desulphurization (WFGD) takes significant effect on the scavenging of PAH in
      both PM10 and gas phases, higher scavenging efficiency were found for less
      volatile PAHs. PAH partitioning is dominated by absorption into organic matter
      and accompanied by adsorption onto PM10 surface. In addition, different
      partitioning mechanism is observed for individual PAHs, which is assumed arising
      from their chemical affinity and vapor pressure. Risk assessment indicates that
      both inhalation and dermal contact greatly contribute to the cancer risk for CFPP
      workers and nearby residents. People working in workshop are exposed to greater
      inhalation and dermal exposure risk than people living in nearby vicinity and
      working office. 

PMID- 26298852
TI  - Linking Ah receptor mediated effects of sediments and impacts on fish to key
      pollutants in the Yangtze Three Gorges Reservoir, China - A comprehensive
      perspective.
AB  - The Three Gorges Reservoir (TGR), created in consequence of the Yangtze River's
      impoundment by the Three Gorges Dam, faces numerous anthropogenic impacts that
      challenge its unique ecosystem. Organic pollutants, particularly aryl hydrocarbon
      receptor (AhR) agonists, have been widely detected in the Yangtze River, but only
      little research was yet done on AhR-mediated activities. Hence, in order to
      assess effects of organic pollution, with particular focus on AhR-mediated
      activities, several sites in the TGR area were examined applying the "triad
      approach". It combines chemical analysis, in vitro, in vivo and in situ
      investigations to a holistic assessment. Sediments and the benthic fish species
      Pelteobagrus vachellii were sampled in 2011/2012, respectively, to identify
      relevant endpoints. Sediment was tested in vitro with the ethoxyresorufin-O
      deethylase (EROD) induction assay, and in vivo with the Fish Embryo Toxicity Test
      and Sediment Contact Assay with Danio rerio. Activities of phase I (EROD) and
      phase II (glutathione-S-transferase) biotransformation enzymes, pollutant
      metabolites and histopathological alterations were studied in situ in P.
      vachellii. EROD induction was tested in vitro and in situ to evaluate possible
      relationships. Two sites, near Chongqing and Kaixian city, were identified as
      regional hot-spots and further investigated in 2013. The sediments induced in the
      in vitro/in vivo bioassays AhR-mediated activities and embryotoxic/teratogenic
      effects - particularly on the cardiovascular system. These endpoints could be
      significantly correlated to each other and respective chemical data. However,
      particle-bound pollutants showed only low bioavailability. The in situ
      investigations suggested a rather poor condition of P. vachellii, with
      histopathological alterations in liver and excretory kidney. Fish from Chongqing
      city exhibited significant hepatic EROD induction and obvious parasitic
      infestations. The polycyclic aromatic hydrocarbon (PAH) metabolite 1
      hydroxypyrene was detected in bile of fish from all sites. All endpoints in
      combination with the chemical data suggest a pivotal role of PAHs in the observed
      ecotoxicological impacts. 

PMID- 26298853
TI  - Contribution of polycyclic aromatic hydrocarbon (PAH) sources to the urban
      environment: A comparison of receptor models.
AB  - The aim of this study was to evaluate the contribution of the main emission
      sources of PAHs associated with PM2.5, in an urban area of the Rio Grande do Sul
      state. Source apportionment was conducted using both the US EPA Positive Matrix
      Factorization (PMF) model and the Chemical Mass Balance (CMB) model. The two
      models were compared to analyze the source contributions similarities and
      differences, their advantages and disadvantages. PM2.5 samples were collected
      continuously over 24h using a stacked filter unit at 3 sampling sites of the
      urban area of the Rio Grande do Sul state every 15days between 2006 and 2008.
      Both models identified the main emission sources of PAHs in PM2.5: vehicle fleet
      (diesel and gasoline), coal combustion, wood burning, and dust. Results indicated
      similar source contribution amongst the sampling sites, as expected because of
      the proximity amongst the sampling sites, which are under the influence of the
      same pollutants emitting sources. Moreover, differences were observed in obtained
      sources contributions for the same data set of each sampling site. The PMF model
      attributed a slightly greater amount of PAHs to the gasoline and diesel sources,
      while diesel contributed more in the CMB results. The results were comparable
      with previous works of the region and in accordance with the characteristics of
      the study area. Comparison between these receptor models, which contain different
      physical constraints, is important for understanding better PAH emissions sources
      in order to reduce air pollution. 

PMID- 26298854
TI  - Toxicological findings in three cases of suicidal asphyxiation with helium.
AB  - INTRODUCTION: Toxicological findings in deaths by asphyxiation due to a pure
      inert gas like helium are rare. We present three suicide cases of asphyxial death
      attributed to anoxia caused by inhalation of helium in a plastic bag positioned
      over the head. METHODS: In one case, lung tissue, brain tissue and heart blood
      were obtained during standard autopsy procedures. In two cases, samples were
      obtained differently: heart blood, femoral blood, brain tissue, lung tissue
      and/or air from the lungs were directly sealed into headspace vials during
      autopsy. Air from the lungs was collected using a syringe and transferred into an
      aluminum gas sampling bag which was heat sealed as soon as possible. Semi
      quantitative gas analyses were performed using headspace gas chromatography
      thermal conductivity detection (HS-GC/TCD) with a molsieve column capable of
      separating permanent gasses. Nitrogen was used as carrier gas. RESULTS: In the
      first case no helium was detected in lung tissue, brain tissue and heart blood.
      In the second case the presence of helium was detected in lung tissue
      (approximately 5% helium in gaseous phase) but not in femoral blood. In the third
      case the presence of helium was detected in air from the lungs (0.05%), lung
      tissue (0.4%), brain tissue (0.1%) and heart blood (0.04%). CONCLUSIONS: Helium
      is easily lost if sampling is not performed properly. The presented cases suggest
      that quick sample collection of various matrices during autopsy is suitable to
      detect gasses like helium in postmortem cases. Use of HS-GC/TCD enables to detect
      an inert gas like helium.

PMID- 26298855
TI  - Multi-modality sparse representation-based classification for Alzheimer's disease
      and mild cognitive impairment.
AB  - BACKGROUND AND OBJECTIVE: The discrimination of Alzheimer's disease (AD) and its
      prodromal stage known as mild cognitive impairment (MCI) from normal control (NC)
      is important for patients' timely treatment. The simultaneous use of multi
      modality data has been demonstrated to be helpful for more accurate
      identification. The current study focused on extending a multi-modality algorithm
      and evaluating the method by identifying AD/MCI. METHODS: In this study, sparse
      representation-based classification (SRC), a well-developed method in pattern
      recognition and machine learning, was extended to a multi-modality classification
      framework named as weighted multi-modality SRC (wmSRC). Data including three
      modalities of volumetric magnetic resonance imaging (MRI), fluorodeoxyglucose
      (FDG) positron emission tomography (PET) and florbetapir PET from the Alzheimer's
      disease Neuroimaging Initiative database were adopted for AD/MCI classification
      (113 AD patients, 110 MCI patients and 117 NC subjects). RESULTS: Adopting wmSRC,
      the classification accuracy achieved 94.8% for AD vs. NC, 74.5% for MCI vs. NC,
      and 77.8% for progressive MCI vs. stable MCI, superior to or comparable with the
      results of some other state-of-the-art models in recent multi-modality
      researches. CONCLUSIONS: The wmSRC method is a promising tool for classification
      with multi-modality data. It could be effective for identifying diseases from NC
      with neuroimaging data, which could be helpful for the timely diagnosis and
      treatment of diseases.

PMID- 26298856
TI  - Comparison of risk factors for acute worsening renal function in heart failure
      patients with and without preserved ejection fraction.
AB  - OBJECTIVE: We compared the risk factors for acute worsening renal function (AWRF)
      in patients with acute decompensated heart failure with preserved ejection
      fraction (HFpEF) versus those with reduced ejection fraction (HFrEF). METHODS: We
      retrospectively studied 181 consecutive patients. AWRF was defined as a rise in
      serum creatinine of >=0.3 mg/dL from admission to day 3. Potential risk factors
      of AWRF were identified in univariate analyses; then logistic regression analysis
      with backward stepwise selection was performed. RESULTS: In the present study of
      limited sample size, 46% had HFpEF (EF>=50%) and 54% had HFrEF (EF<50%). In the
      HFpEF group, history of hypertension (odds ratio [OR] 32.46, 95% CI 2.39-440.12,
      P=0.009), the increased serum potassium value at admission (OR 4.61, 95% CI 1.14
      18.73, P=0.032), and the pretreatment with calcium channel blocker (OR 8.52, 95%
      CI 1.21-60.09, P=0.032) were independent risk factors (defined as P<0.05 and
      OR>1.01) for AWRF. In contrast, diastolic blood pressure at admission (OR 1.07,
      95% CI 1.02-1.13, P=0.004) was the sole independent risk factor for AWRF in the
      HFrEF group. CONCLUSIONS: Hypertension was associated with AWRF in both HFpEF and
      HFrEF patients. A history of hypertension was more important than elevated blood
      pressure at admission as a risk factor for AWRF in HFpEF, whereas the reverse was
      observed for HFrEF. Among antihypertensive drugs, pretreatment with calcium
      channel blocker was an independent risk factor for AWRF in HFpEF, but not in
      HFrEF.

PMID- 26298857
TI  - Response to letter to the editor: "(Chlan & Heiderscheit 2015) Re: Gullick J,
      Kwan X. Patient-directed music therapy reduces anxiety and sedation exposure in
      mechanically-ventilated patients: a research critique. Aust Crit Care 2015;28:103
      5".

PMID- 26298858
TI  - Occurrence of C. botulinum in healthy cattle and their environment following
      poultry botulism outbreaks in mixed farms.
AB  - Ten cattle farms located in an area with a recent history of poultry botulism
      outbreaks were investigated to evaluate the occurrence of toxigenic C. botulinum
      in healthy cattle. Environmental samples in the 10 cattle farms and bovine fecal
      contents in farms with a confirmed environmental contamination were collected.
      Detection of C. botulinum toxin genes C, D, C/D, D/C and E was performed using
      real-time PCR. 4.9% (7/143) of the environmental samples collected in the 10
      investigated cattle farms were positive for C. botulinum type C/D. Theses samples
      (boot-swabs in stalls and on pasture and water of a stream) were collected in 3
      different farms. One cow dung sample and 3 out of 64 fecal contents samples
      collected in a single farm were also positive for C. botulinum type C/D. This
      study demonstrates that cattle are probably indirectly contaminated via poultry
      botulism in the area and that they can be intermittent carrier of C. botulinum
      type C/D after poultry botulism outbreaks in mixed farms. 

PMID- 26298859
TI  - Respiratory syncytial virus nonstructural proteins 1 and 2 are crucial pathogenic
      factors that modulate interferon signaling and Treg cell distribution in mice.
AB  - Respiratory syncytial virus (RSV) nonstructural (NS) proteins 1 and 2 have
      multiple functions in suppressing the innate immune response and modulating T
      helper cell subset differentiation. However, little is known about the roles of
      NS proteins as independent virulence factors. We investigated the effects of
      recombinant NS1- and NS2-expressing plasmids on the pathogenesis of murine
      respiratory tissues and splenetic Foxp3+ regulatory T (Treg) cell distribution.
      Both NS proteins caused weight loss in mice, and NS2 transfection resulted in a
      persistent weight loss. NS1 dramatically suppressed the induction of interferon
      beta and interferon-induced GTP-binding protein Mx1. NS1 and NS2 demonstrated
      different effects in regulating Treg cell differentiation; NS2 increased the
      proportion of Tregs, whereas NS1 suppressed it. Inhibiting either NS1 or NS2
      alleviated the pathology of lung tissues. Thus, NS1 and NS2 are independent
      pathogenic factors and could be targets for therapeutic strategies in treating
      RSV infection. 

PMID- 26298860
TI  - Blunted inflammatory and mucosal IgA responses to pneumonia virus of mice in
      C57BL/6 neonates are correlated to reduced protective immunity upon re-infection
      as elderly mice.
AB  - Respiratory syncytial virus is a major cause of bronchiolitis in infants and
      pneumonia virus of mice (PVM) causes similar disease in mice. The impact of PVM
      infection in BALB/c and C57BL/6 neonates, and upon re-infection as elderly mice,
      was compared. As previously shown for adult mice, PVM caused more disease in
      BALB/c than in C57BL/6 neonates. After PVM-15 infection BALB/c neonates showed
      higher production of inflammatory mediators, more influx of plasmacytoid
      dendritic cells and higher IFN-alpha expression, and more IgA in the lungs than
      C57BL/6 neonates. After re-infection as elderly, BALB/c mice developed virus
      neutralizing antibodies in serum and lung, and were protected from clinical
      disease, whereas C57BL/6 mice did not develop an anamnestic response and were not
      protected. These results suggest that an effective local innate response, as well
      as priming of mucosal adaptive responses in neonates after PVM-15 infection is
      correlated to decreased susceptibility and protection upon re-infection. 

PMID- 26298861
TI  - Women with double primary cancers of the colorectum and endometrium: do they have
      Lynch syndrome?
AB  - OBJECTIVE: The aim of this study was to determine the clinical characteristics of
      women with double primary cancers of the colorectum and endometrium and assess
      the probability of Lynch syndrome. STUDY DESIGN: We identified 15 women with
      paraffin-embedded blocks available who were diagnosed, treated and followed for
      double primary colorectal and endometrial cancers at in a single institution
      between 1994 and 2014. If there was a family history that met the revised
      Amsterdam criteria for Lynch syndrome, the woman was considered to have
      'clinically defined Lynch syndrome'. If immunohistochemical (IHC) loss of
      expression of mismatch repair genes (MLH1, MSH2, MSH6, or PMS2) or high
      microsatellite instability (MSI) was demonstrated in molecular testing, the case
      was considered 'suspected Lynch syndrome'. RESULTS: The incidence of clinically
      defined Lynch syndrome according to the revised Amsterdam criteria was 66% (8 of
      15). All 8 of the women clinically diagnosed with Lynch syndrome had either
      abnormal IHC loss or MSI-high, indicating a suspected Lynch syndrome.
      Furthermore, 27% (4 of 15) experienced second primary colorectal cancer or other
      Lynch syndrome-related cancers. Overall, 66% (10 of 15) met the criteria for
      clinically defined Lynch syndrome or suspected Lynch syndrome. CONCLUSIONS: Based
      on our findings, a large percentage (66%) of women with double primary cancers of
      the colorectum and endometrium are likely to be diagnosed with Lynch syndrome.

PMID- 26298862
TI  - Manual development: A strategy for identifying core components of integrated
      health programs.
AB  - Integrated care models are gaining popularity as a clinical strategy to reduce
      costs and improve client outcomes; however, implementation of such complex models
      requires an understanding of programmatic core components essential to producing
      positive outcomes. To promote this understanding, evaluators can work
      collaboratively with organization staff and leaderships to gather information on
      program implementation, adaptations, organizational buy-in, and project outcomes.
      In 2011, SAMHSA funded two Miami health clinics to implement integrated care
      models in co-located settings. Changes in the federal healthcare landscape, non
      Medicaid expansion for Florida, and the complexity of projects goals led
      evaluators to facilitate a core component review as part of evaluation. A manual
      was developed throughout the project and captured a description, adaptations,
      inputs needed, lessons learned, and sustainability for each integrated care
      component. To increase chances for program success, evaluators should institute a
      method to better define core components of new programs and implementation
      adaptations, while keeping program replication in mind. Breaking down the program
      structurally gave the evaluation utility for stakeholders, and ultimately served
      as a resource for organizations to better understand their program model. The
      manual also continues to serve as a dissemination and replication source for
      other providers looking to implement integrated care. 

PMID- 26298863
TI  - Genetic polymorphisms in the UDP-glucuronosyltransferase UGT1A7 gene in patients
      with acute liver failure after kava-kava consumption.

PMID- 26298864
TI  - Novel binuclear MU-oxo diruthenium complexes combined with ibuprofen and
      ketoprofen: Interaction with relevant target biomolecules and anti-allergic
      potential.
AB  - This work presents the synthesis and characterization of two novel binuclear
      ruthenium compounds of general formula [Ru2O(carb)2(py)6](PF6)2, where
      py=pyridine and carb are the non-steroidal anti-inflammatory drugs ibuprofen (1)
      and ketoprofen (2). Both complexes were characterized by ESI-MS/MS spectrometry.
      The fragmentation patterns, which confirm the proposed structures, are presented.
      Besides that, compounds 1 and 2 present the charge transfer transitions within
      325-330nm; and the intra-core transitions around 585nm, which is the typical
      spectra profile for [Ru2O] analogues. This suggests the carboxylate bridge has
      little influence in their electronic structure. The effects of the diruthenium
      complexes on Ig-E mediated mast cell activation were evaluated by measuring the
      enzyme beta-hexosaminidase released by mast cells stimulated by antigen. The
      inhibitory potential of the ketoprofen complex against mast cell stimulation
      suggests its promising application as a therapeutic agent for treating or
      preventing IgE-mediated allergic diseases. In addition, in vitro metabolism
      assays had shown that the ibuprofen complex is metabolized by the cytochrome P450
      enzymes. 

PMID- 26298865
TI  - Different zinc(II) complex species and binding modes at Abeta N-terminus drive
      distinct long range cross-talks in the Abeta monomers.
AB  - The present study addresses the reconstruction of the free-energy landscapes of
      amyloid-beta1-42 (Abeta42) coordinated respectively with one and two zinc ions,
      to scrutinize whether different Abeta-zinc complex species, i.e., mononuclear and
      dinuclear metal complexes, induce different Abeta conformation features. We found
      a subtle switch of intramolecular interactions, depending both on the zinc
      coordination environment and on the peptide to zinc stoichiometric ratio. On the
      one side, hairpin-like structures are predominant in mononuclear complexes, where
      a salt-bridge that involves Lys28-Glu22 and Lys16-Asp23 is stabilized. On the
      other side, elongated conformations are instead stabilized in the dinuclear zinc
      complexes. Experimental studies of atomic force microscopy as well as of zinc
      Abeta complex species distribution diagrams provide evidence that the theoretical
      calculations can be rationalized in terms of the correlation between the
      increased amount of amorphous aggregates and the Abeta/Zn(2+) ratio. 

PMID- 26298866
TI  - Prognostic value of extravascular lung water assessed with lung ultrasound score
      by chest sonography in patients with acute respiratory distress syndrome.
AB  - BACKGROUND: The prognostic value of extravascular lung water indices (EVLWI) has
      been widely investigated, which is determined by lung ultrasound B-lines.
      However, the clinical value of lung ultrasound B-lines for determining
      prognosis/intensive care unit (ICU) outcomes in patients with acute respiratory
      distress syndrome (ARDS) has been rarely reported. METHODS: Twenty-one ARDS
      patients admitted to the ICU of Fu Xing Hospital underwent both lung
      ultrasonography and pulse index continuous cardiac output (PiCCO) monitoring on
      the first, second, and third days after diagnosis. The correlation between lung
      ultrasound score (LUS) and EVLWI measured by the PiCCO system was investigated.
      The prognostic clinical value of lung ultrasonography in ARDS patients was
      explored. Chest ultrasound was performed using the 12 regions method. The
      comprehensive score of lung ultrasound was determined according to the level of
      lung aeration. RESULTS: With ICU mortality as the end point, 21 patients were
      divided into a survivor group (8 patients, 39.1 %) and a non-survivor group (13
      patients, 61.9 %). Significant positive linear correlations were found between
      LUS and EVLWI, including predicted body weight (r (2) = 0.906), sequential organ
      failure assessment score (r (2) = 0.815), lung injury score (r (2) = 0.361), and
      PaO2/FiO2 (r (2) = 0.472). Significantly different LUSs were found between the
      non-survivor and survivor groups (F = 77.64, P <0.01) by repeated-measures
      analysis of variance. There were no significant differences between the two
      groups on different days. The areas under the receiver operating characteristic
      curves of LUS and EVLW measured by PiCCO were 0.846 (P < 0.01) and 0.918 (P <
      0.01), respectively. The cut-off of LUS for prognosis prediction was 16.5.
      CONCLUSIONS: Lung ultrasonography is a non-invasive, economic, simple, user
      friendly, and radiation-free bedside method for predicting the prognosis of ARDS
      patients. Early measurement of LUS is a better prognostic indicator in patients
      with ARDS.

PMID- 26298867
TI  - The bone mineral content alterations in pediatric patients medicated with
      levetiracetam, valproic acid, and carbamazepine.
AB  - AIM: The negative effect of antiepileptic drugs on bone health has been
      previously documented. However, which antiepileptic drug is safer in regard to
      bone health is still questionable. Our aims were to investigate the bone mineral
      density alterations in pediatric patients who receive antiepileptic medication
      for a minimum of two years and to compare the results of these drugs. MATERIALS
      AND METHODS: Fifty-nine patients (32 males, 27 females; mean age: 8.6+/-4.6years)
      and a control group (13 males, 7 females; mean age: 7.6+/-3.3years) were included
      in the study. The patients were receiving necessarily the same antiepileptic
      drugs (AEDs) for at least two years, and none of the patients had mental
      retardation or cerebral palsy. The patients were divided into three groups: group
      1 (patients receiving levetiracetam (LEV), n=20), group 2 (patients receiving
      carbamazepine (CBZ), n=11), and group 3 (patients receiving valproic acid (VPA),
      n=28). Plasma calcium (Ca), phosphorus (P), parathyroid hormone (PTH), alkaline
      phosphatase (ALP), vitamin D levels, and bone mineral density (BMD) values of
      femur and vertebras (L1-4) and z-scores (comparative results of BMD values of the
      patients with the age- and gender-matched controls in device database) of the
      groups were compared. RESULTS: The differences between P, PTH, ALP and age, Ca
      and BMD results, and vitamin D levels of the patients in all four groups was not
      statistically significant according to Kruskal-Wallis test (p>0.05). The z-score
      levels of all the patient and control groups were also not statistically
      significantly different compared with each other. CONCLUSION: In contrast to
      previous reports in pediatric patients, our study has documented that there is
      not a considerable bone loss in patients receiving long-term AED medication.
      Although levetiracetam has been proposed as bone-protecting medication, we did
      not observe any difference between AEDs regarding bone mineral density after two
      years of treatment.

PMID- 26298868
TI  - Family communication in the context of pediatric epilepsy: A systematic review.
AB  - In childhood chronic illness, family communication can impact the child's and
      parents' psychosocial well-being. However, little is known about family
      communication in the context of epilepsy in childhood. The aim of this systematic
      review was to identify the existing evidence available on communication
      strategies adopted by families living with childhood epilepsy, including; the
      facilitators, barriers and challenges experienced by families when choosing to
      communicate, or not, about epilepsy; and the consequences of this communication.
      Papers published in the English language prior to March 2015 were identified
      following a search of six electronic databases: PubMed, MEDLINE, Web of Science,
      PsycINFO, CINAHL, and Scopus. Studies were included if they involved a sample of
      parents of children with epilepsy or children/young people with epilepsy (0
      18years of age) and used qualitative, quantitative, or mixed methods. Following a
      comprehensive search and screening process, 26 studies were identified as
      eligible for inclusion in the review. No studies identified specific
      communication strategies adopted by families living with childhood epilepsy. Some
      studies found that talking about epilepsy with family members had positive
      consequences (e.g., communication as an effective coping strategy), with no
      negative consequences reported in any of the studies. The main barrier to
      communication for parents was an unwillingness to use the word "epilepsy" because
      of the perceived negative social connotations associated with the health
      condition. For children with epilepsy, barriers were as follows: parental desire
      to keep epilepsy a secret, parents' tendency to deny that the child had epilepsy,
      parental overprotection, and parents' tendency to impose greater restrictions on
      the child with epilepsy than on siblings without epilepsy. Future research
      investigating the communication strategies of families living with epilepsy is
      needed in order to create effective communication-based interventions for
      discussing epilepsy within the home. 

PMID- 26298869
TI  - G2E3 attenuating replicative stress.

PMID- 26298870
TI  - Platelet-activating protamine-heparin-antibodies lead to higher protamine demand
      in patients undergoing cardiac surgery.
AB  - OBJECTIVES: Platelet-activating antibodies against protamine-heparin-complexes
      were described in patients undergoing cardiac surgery, but their clinical
      consequences remain unclear. This prospective single-center observational study
      aimed to describe the prevalence and clinical consequences of protamine-heparin
      complex antibodies in patients undergoing cardiac surgery with cardiopulmonary
      bypass. METHODS: A total of 200 patients undergoing cardiac surgery with
      cardiopulmonary bypass were included. Blood samples were collected preoperatively
      and 1 hour, 24 hours, and 7 days after weaning from cardiopulmonary bypass. All
      sera were tested for the presence of protamine-heparin-complex antibodies using a
      modified heparin-induced platelet-activation assay. Specific Fcgamma receptor IIa
      dependent platelet activation was confirmed by repeated testing in the presence
      of the Fcgamma receptor IIa-blocking antibody IV.3. RESULTS: Samples from 185
      patients were obtained, of whom 24 patients (13%) were positive for protamine
      heparin-complex antibodies preoperatively. In all positive samples, functional
      reactivity was reversible in the presence of IV.3. Although patients with a
      preoperative presence of protamine-heparin-complex antibodies were significantly
      older compared with patients negative for protamine-heparin-complex antibodies
      (73 +/- 9.8 years vs 68 +/- 10 years, P = .037), no other potential risk factors
      were identified at 1 day before operation. Patients with protamine-heparin
      complex antibodies required significantly more protamine to neutralize heparin
      (47.66 mg vs 41.67 mg, P = .027). Protamine-heparin-complex antibodies have no
      significant influence on perioperative platelet numbers, bleeding complications,
      transfusion requirement, thromboembolic events, major cardiovascular and
      cerebrovascular events, inflammation parameters, or kidney function. CONCLUSIONS:
      Protamine-heparin-complex antibodies occur frequently in patients undergoing
      cardiac surgery on cardiopulmonary bypass, resulting in specific platelet
      activation in vitro. Protamine-heparin-complex antibodies are associated with
      increased protamine requirement after cardiopulmonary bypass and possibly slower
      recovery of platelet numbers.

PMID- 26298871
TI  - The diabetes epidemic and its effect on cardiac surgery practice.

PMID- 26298872
TI  - Early surgical intervention versus watchful waiting and outcomes for asymptomatic
      severe aortic regurgitation.
AB  - OBJECTIVES: The management of asymptomatic patients with severe aortic
      regurgitation remains controversial. Accordingly, the aim of the present study
      was to assess the long-term outcomes and incidence of cardiac complications among
      asymptomatic patients with severe aortic regurgitation who underwent operation
      early, in the absence of any class I or class IIa guideline triggers, or were
      managed conservatively and eventually underwent operation whenever these triggers
      appeared. METHODS: A total of 160 consecutive asymptomatic patients (50 +/- 17
      years) with severe aortic regurgitation were prospectively followed up for a
      median of 7.2 years. Overall and cardiovascular survivals and the need for repeat
      aortic regurgitation surgery were evaluated in an "early surgery" group (n = 91)
      and a "conservatively managed" group (n = 69). RESULTS: Ten-year overall (91% +/-
      4% vs 89% +/- 5%, P = .87) and cardiovascular (96% +/- 2% vs 96% +/- 3%, P = .79)
      survivals were similar among the early surgery and conservatively managed groups.
      Conservatively managed patients were further sub-stratified according to the
      regularity and quality of their follow-up. Patients who were regularly followed
      up by a certified cardiologist had a better 10-year overall survival than
      patients undergoing no or a looser follow-up (95% +/- 5% vs 79% +/- 10%, P =
      .045). Multivariate Cox proportional hazards analysis identified age (P = .003)
      and male gender (P = .024) as independent predictors of survival. Early surgical
      management was not a predictor of outcome (P = .45). CONCLUSIONS: Our results
      show that the outcome of asymptomatic patients with severe aortic regurgitation
      is not different between an early surgical and a more conservative strategy,
      provided that the conservatively managed patients are regularly followed up and
      timely referred to surgery as soon as operative triggers develop. This suggests
      that surgery should not be recommended in patients with aortic regurgitation who
      do not meet current guidelines for intervention.

PMID- 26298873
TI  - [Mental health and primary care in Mexico. Opportunities and challenges].
AB  - OBJECTIVE: To present the conditions that favour or limit the integration of
      mental health into health centres, based on the perceptions of health workers and
      on observations made by researchers. DESIGN: A study was conducted between April
      2012 and February 2014 using a non-participant observation technique plus
      interviews with health professionals. SETTING: Descriptive exploratory study
      conducted in 19 health centres in Mexico City. METHOD: The selection of centres
      and participants was intentional, followed by the snowball technique in order to
      reach data saturation. Two guides were use, one for collecting information during
      the observation and the other one for interviews. The observations were
      registered in field notes, while the interviews were audio recorded. All
      collected information was stored in Word files. The analysis of field notes
      consisted of three levels of reading, and the interview analysis was based on
      "categorisation of meanings" proposed by Kvale (1996). RESULTS: The aspects that
      favour or limit the integration of mental health services involve three broad
      categories: a) programs and methods that organise services, b) infrastructure and
      material resources and, c) human and information resources. CONCLUSIONS: Actions
      targeted at including mental health into productivity reports and into already
      established goals, would contribute to the integration of mental health care, as
      well as promoting the idea that mental health is part of overall health, and to
      increase the public investment in health.

PMID- 26298874
TI  - [Cost-effectiveness of the deep vein thrombosis diagnosis process in primary
      care].
AB  - OBJECTIVE: To analyse the cost effectiveness of the application of diagnostic
      algorithms in patients with a first episode of suspected deep vein thrombosis
      (DVT) in Primary Care compared with systematic referral to specialised centres.
      DESIGN: Observational, cross-sectional, analytical study. LOCATION: Patients from
      hospital emergency rooms referred from Primary Care to complete clinical
      evaluation and diagnosis. PARTICIPANTS: A total of 138 patients with symptoms of
      a first episode of DVT were recruited; 22 were excluded (no Primary Care report,
      symptoms for more than 30 days, anticoagulant treatment, and previous DVT). Of
      the 116 patients finally included, 61% women and the mean age was 71 years. MAIN
      MEASUREMENTS: Variables from the Wells and Oudega clinical probability scales, D
      dimer (portable and hospital), Doppler ultrasound, and direct costs generated by
      the three algorithms analysed: all patients were referred systematically,
      referral according to Wells and Oudega scale. RESULTS: DVT was confirmed in
      18.9%. The two clinical probability scales showed a sensitivity of 100% (95% CI:
      85.1 to 100) and a specificity of about 40%. With the application of the scales,
      one third of all referrals to hospital emergency rooms could have been avoided
      (P<.001). The diagnostic cost could have been reduced by ? 8,620 according to
      Oudega and ? 9,741 according to Wells, per 100 patients visited. CONCLUSION: The
      application of diagnostic algorithms when a DVT is suspected could lead to better
      diagnostic management by physicians, and a more cost effective process.

PMID- 26298876
TI  - [Molecular genetics is used to diagnose and treat central nerve system
      disorders].

PMID- 26298877
TI  - [Clinical aspect of ear pain].

PMID- 26298875
TI  - Effectiveness of imaging modalities for screening IgG4-related dacryoadenitis and
      sialadenitis (Mikulicz's disease) and for differentiating it from Sjogren's
      syndrome (SS), with an emphasis on sonography.
AB  - INTRODUCTION: The aim of this study was to clarify the effectiveness of various
      imaging modalities and characteristic imaging features in the screening of IgG4
      related dacryoadenitis and sialadenitis (IgG4-DS), and to show the differences in
      the imaging features between IgG4-DS and Sjogren's syndrome (SS). METHODS: Thirty
      nine patients with IgG4-DS, 51 with SS and 36 with normal salivary glands were
      enrolled. Images of the parotid and submandibular glands obtained using
      sonography, 2-[(18)F]-fluoro-2-deoxy-D-glucose positron emission
      tomography/computed tomography (FDG-PET/CT), computed tomography (CT) and
      magnetic resonance imaging (MRI) were retrospectively analyzed. Six oral and
      maxillofacial radiologists randomly reviewed the arranged image sets under
      blinded conditions. Each observer scored the confidence rating regarding the
      presence of the characteristic imaging findings using a 5-grade rating system.
      After scoring various findings, diagnosis was made as normal, IgG4-DS or SS,
      considering all findings for each case. RESULTS: On sonography, multiple
      hypoechoic areas and hyperechoic lines and/or spots in the parotid glands and
      obscuration of submandibular gland configuration were detected mainly in patients
      with SS (median scores 4, 4 and 3, respectively). Reticular and nodal patterns
      were observed primarily in patients with IgG4-DS (median score 5). FDG-PET/CT
      revealed a tendency for abnormal (18)F-FDG accumulation and swelling of both the
      parotid and submandibular glands in patients with IgG4-DS, particularly in the
      submandibular glands. On MRI, SS had a high score regarding the findings of a
      salt-and-pepper appearance and/or multiple cystic areas in the parotid glands
      (median score 4.5). Sonography showed the highest values among the four imaging
      modalities for sensitivity, specificity and accuracy. There were significant
      differences between sonography and CT (p = 0.0001) and between sonography and FDG
      PET/CT (p = 0.0058) concerning accuracy. CONCLUSIONS: Changes in the
      submandibular glands affected by IgG4-DS could be easily detected using
      sonography (characteristic bilateral nodal/reticular change) and FDG-PET/CT
      (abnormal (18)F-FDG accumulation). Even inexperienced observers could detect
      these findings. In addition, sonography could also differentiate SS.
      Consequently, we recommend sonography as a modality for the screening of IgG4-DS,
      because it is easy to use, involves no radiation exposure and is an effective
      imaging modality.

PMID- 26298878
TI  - [IgG4 associated disorder involved with otorhinolaryngologic diseases].

PMID- 26298879
TI  - [Diagnose and treatment of nasal sinus mycoses].

PMID- 26298880
TI  - [Prevention and treatment of congenital rubella syndrome].

PMID- 26298881
TI  - [Surgery and postoperative treatment of eosinophilic nasal sinustis].

PMID- 26298882
TI  - Addendum to report of the Global Advisory Committee on Vaccine Safety (GACVS), 10
      11 June 20151. Safety of CYD-TDV dengue vaccine.

PMID- 26298883
TI  - Progress towards poliomyelitis eradication in Nigeria, January 2014- July 2015.

PMID- 26298884
TI  - Monthly report on dracunculiasis cases, January-June 2015.

PMID- 26298885
TI  - [Head and neck tumor].

PMID- 26298886
TI  - [Transoral robotic surgery: TORS].

PMID- 26298887
TI  - [Immunotherapy for head and neck cancer].

PMID- 26298888
TI  - [Molecular targeting treatment for thyroid cancer].

PMID- 26298889
TI  - [Getting out of tobacco].

PMID- 26298890
TI  - [Tacrolimus in atopic dermatitis: restricting reimbursement was wrong].

PMID- 26298891
TI  - [The use of electronic cigarettes should be carefully supervised].

PMID- 26298892
TI  - [Vascular liver diseases].
AB  - Vascular liver diseases include a group of rare, even exceptional, diseases:
      portal vein thrombosis, obliterative portal venopathy and Budd-Chiari syndrome.
      Here we will discuss in detail the least rare, portal vein thrombosis, of which
      the main complication (when recanalization was not reached during the acute
      phase) is esophageal variceal bleeding. However, a prothrombotic condition
      (including myeloproliferative syndrome) is often the cause of portal vein
      thrombosis. Thereby, in certain cases, a long-term anticoagulation is necessary
      despite the bleeding risk. Aside from these rare diseases, vascular and
      thrombotic involvement participate in the pathophysiology of cirrhosis, and
      anticoagulant treatment might be beneficial in some patients.

PMID- 26298893
TI  - [Ebola virus disease].

PMID- 26298894
TI  - [Bariatric surgery in teenagers].
AB  - Bariatric surgery in teen-agers is increasing. This surgical option in the
      severely obese adolescent raises a series of questions on clinical pathway and
      ethics. It should be realized in highly specialized centers gathering skills in
      bariatric surgery, pediatric endocrinology and nutrition and psychology. It is a
      longstanding multifocal and proactive management including the transition to
      adulthood. Expert centers should be identified.

PMID- 26298895
TI  - [Can the duration of antibiotic therapy be reduced to 4 days in intra-abdominal
      infections?].

PMID- 26298896
TI  - [Colorectal cancer: a heterogeneous complex model].

PMID- 26298897
TI  - [Epidemiology of colorectal cancer].
AB  - The incidence of colorectal cancer increased in France until the 2000s' then
      decreased. Time trends in incidence for this cancer varied according to its
      sublocation along the gut. Incidence increased for right and left colon cancers,
      whereas it remained stable for sigmoid cancers in males and decreased in females.
      Incidence decreased over time for rectal cancers. The proportion of colorectal
      cancer in the overall French cancer prevalence is 12%. In 2008, 121,000 patients
      had a colorectal cancer diagnosed in the 5 previous years. The cumulative risk of
      colorectal cancer increased from 3.9% for males born around 1900 to 4.9% for
      those born around 1930 and then slightly decreased, being 4.5% among those born
      around 1950. It remained at the same level for females and was 2.9% for those
      born around 1950. The prognosis of colorectal cancer improved over time. Net 5
      year survival increased in males from 53% for cancers diagnosed between 1989 and
      1991 to 58% for those diagnosed between 2001 and 2004. The highest improvement of
      10 year survival rates concerned left colon and rectosigmoid junction (+19% in a
      decade). The progressive set up of national colorectal screening since the early
      2000's and the introduction of recent immunological tests in 2015 should decrease
      the mortality for this cancer and, at term, should decrease its incidence too.

PMID- 26298898
TI  - [Screening and prevention of colorectal cancer].
AB  - Population-based studies have shown that guaiac faecal occult blood testing
      followed by colonoscopy in case of positivity can reduce colorectal cancer
      mortality. However attention has been given for alternative tests in particular
      to immunochemical faecal occult blood tests. It is now clear from available data
      that immunochemical tests outperform guaiac tests. They should be preferred for
      CRC screening. The one sample strategy has been adopted in most screening
      programmes. Given the superior performance characteristics of immunochemical, it
      is reasonable to assume that an organized programme using this type of test would
      lead to a greater reduction in colorectal cancer mortality and possibly of
      colorectal cancer incidence. Epidemiological studies allow us to define subjects
      at very high risk (genetic origin) and high risk for colorectal cancer.
      Colonoscopy screening is recommended in first degree relatives of patients with
      colorectal cancer or large adenoma diagnosed before 60 years or with two affected
      first-degree relatives, in subjects with an extended inflammatory bowel disease,
      or with a personal history of large bowel cancer or large adenoma.

PMID- 26298899
TI  - [Surgical treatment of colorectal cancer].
AB  - Any therapeutic decision in colorectal cancer must be taken by multidisciplinary
      coordination meeting. The treatment of non-metastatic colon cancer based on the
      first surgery with complete excision, dissection and respect distal margins. In
      case of node-adjuvant chemotherapy improves survival. For rectal cancer, surgery
      may be preceded by chemo radiotherapy for locally advanced cancers. The sphincter
      preservation rate in entrained teams can reach 90%. The abdominoperineal
      resection is indicated in cases of tumor invading the external sphincter. In
      colorectal cancer the most important prognostic factor is the histological stage
      (invasion of the intestinal wall and lymph node involvement). If the breach only
      affects the mucosal healing is 100%. If the entire wall is reached, node negative
      the survival is 60%. However, if the lymph nodes are affected survival drop 30
      40%. Finally in the presence of synchronous liver metastases curative treatment
      options can be considered and must be defined in the multidisciplinary
      coordination meeting. Surgery of liver metastases can achieve cure rates of 30%
      at 5 years.

PMID- 26298900
TI  - [Peri-operative treatments for rectal cancer].
AB  - Depending on its location or stage, rectal cancer may differ significantly.
      Before any treatment decision a careful work up is mandatory relying mainly on
      endoscopy and imaging (MRI). Surgery according to the TME principle is the
      cornerstone of treatment. Most of the time surgery is associated with external
      beam radiotherapy often combined with concurrent chemotherapy (capecitabine)
      according to the neoadjuvant regimen CAP 50 (5 weeks long). It is sometimes
      possible to escalate safely the dose of irradiation using contact X-ray
      brachytherapy 50 Kv or Iridium 192 interstitial brachytherapy. Adjuvant
      chemotherapy may be given in case of pejorative pathological findings but its
      benefit is not yet proven in contrast with colon cancer. Local recurrences are
      becoming unusual as is permanent APE surgery with permanent stoma. To reduce the
      risk of distant metastasis clinical trials are testing first line chemotherapy in
      T3-4 lesions. For early stage (T2-"small" T3) clinical trials try to achieve
      organ preservation. Intensification of CAP 50 either with more chemotherapy or
      radiation dose escalation using contact X-ray aim at achieving a clinical
      complete response followed by local excision or close surveillance.

PMID- 26298901
TI  - [Adjuvant treatment for resected colon cancer].
AB  - Adjuvant treatment has clearly demonstrated its efficacy and safety in resected
      colon cancer patients, saving thousands of lives every year worldwide. Six months
      adjuvant chemotherapy combining 5FU and oxaliplatin (FOLFOX or XELOX regimens) is
      indicated in stage III colon cancer after surgical removal of the primary tumor.
      The benefit of adjuvant chemotherapy seems less evident in stage II colon cancer,
      but this treatment should be discussed in patients with "high risk" factors for
      recurrence. Patient's age is also an important factor for adjuvant treatment
      decision. The challenge in the future will be to establish predictive and
      prognostic scores able to offer an even more personalized adjuvant therapeutic
      approach.

PMID- 26298902
TI  - [Management of metastatic colorectal cancer].
AB  - Prognosis of metastatic colorectal cancer has dramatically improved during these
      two last decades, through a better understanding of therapeutic goals and the
      development of news drugs such as biologics. The character resectable,
      potentially resectable or not resectable of colorectal cancer liver metastasis
      should be considered at baseline because it determines the systemic chemotherapy
      which will be conducted. Considering resectable metastasis, 6 courses of FOLFOX
      (5 fluoro-uracil + oxaliplatin) will be administered before and after surgery in
      the goal of "cleaning" the body from the potential micrometastasis. In
      potentially resectable liver metastasis, the objective of the chemotherapy will
      be to get a tumor shrinkage, enabling microscopically complete resection while
      leaving enough functional hepatic parenchyma. In case of unresectable metastasis,
      obtaining a tumor response with an intensive induction chemotherapy is the
      guarantee of a good disease control, and authorizes to light treatment during a
      maintenance period, or a therapeutic break in selected patients, without altering
      the prognosis.

PMID- 26298903
TI  - [Colorectal cancer surgery with curative intent: what surveillance?].
AB  - Colorectal cancer, incidence has increased by more than 50% over the past 30
      years. On the other hand, over the same period, the number of deaths remained
      stable, which reflects major therapeutic progress. Around 75% of patients may
      benefit from surgical resection with curative intent. Among them, nearly 30% of
      stage II and more than 55% of stage III patients present a loco-regional or
      distant recurrence or a metachronous cancer within 5 years after initial
      treatment. This high risk of recurrence raises the question of postoperative
      monitoring in order to detect early recurrences and metachronous cancers at a
      curable stage. The annual incidence of adenomas is low and the cumulative risk of
      endoluminal recurrences or metachronous cancer is very low. Therefore intensive
      endoscopic monitoring is not useful. Postoperative monitoring of distant
      recurrences is poorly codified. However, despite their limits, recent trials and
      meta-analysis suggest that survival is increased thanks to clinical monitoring
      combined with hepatic and pulmonary imaging. CEA measurement usefulness remains
      debated. A large randomised trial of monitoring strategy ended recently and
      should provide answers. This report focused on the monitoring mode after curative
      resection.

PMID- 26298904
TI  - [Colorectal cancer biology].
AB  - In colorectal cancer (CRC), genetic alterations are involved in disease
      progression from adenoma to carcinoma and metastatic disease. Three different
      carcinogenesis mechanisms exist: chromosomal instability phenotype (CIN),
      microsatellite instability phenotype (MSI) and the hypermetylator phenotype (CIMP
      for CpG Island methylation phenotype). These molecular alterations lead to signal
      transduction dysfunction, and signaling pathways alterations are involved in
      cancer mechanisms, such as EGFR pathway, WNT/APC pathway, TGFB pathway and p53
      pathway. Recently, molecular signatures have been established, allowing
      distinction of 4 different types of CCR. Finally, circulating biomarkers are
      investigated for molecular characterization.

PMID- 26298905
TI  - [Why look for secondary hypertension?].

PMID- 26298906
TI  - [Iatrogenic and drug-induced hypertension].
AB  - Various toxic or drug agents can induce arterial hypertension, aggravate or limit
      the efficiency of anti-hypertensive drugs. Iatrogenic and drug-induced
      hypertension should be well known by the clinicians and the pharmacists, given
      the impact for driving the management of patients. In the food, an excessive
      alcohol consumption (more than 30 g per day) and more rarely glycerizine (active
      ingredient of the licorice) should be systematically looked for in front of a
      recent hypertension or do not respond to usual treatment. In the list of
      offending medicines, we must remember ethinyl estradiol contained in the
      contraception (oral, vaginal ring or transcutaneous patch), non steroidal anti
      inflammatory drugs, immunosuppressants (cyclosporine, tacrolimus), vascular
      endothelial growth factor and its receptor R2 (avastin, inhibitors of receptor
      tyrosine kinases), recombinant human erythropoietin, sympathomimetics (nasal
      decongestants), anabolic steroids, bromocriptine (inhibitor of lactation),
      psychotropes (tricyclics antidepressants, monoamine oxydase inhibitors). The
      diagnosis of iatrogenic hypertensions should be systematically suspected in front
      of a suggestive clinical context with a meticulous food questioning because these
      hypertensions are partially or fully reversible after exposure stops.

PMID- 26298907
TI  - [Primary aldosteronism].
AB  - Primary aldosteronism affects 6% of hypertensive patients. The diagnosis should
      be suspected in any patient with severe or resistant hypertension or hypertension
      associated with hypokalemia. The screening test consists on the assessment of the
      aldosterone to renin ratio. In case of an elevated ratio, the diagnosis of
      primary aldosteronism is confirmed by either elevated concentrations of basal
      plasma and/or urinary aldosterone or absence of suppression of aldosterone during
      dynamic test (including the saline infusion test). CT aims to ensure the absence
      of adrenal carcinoma and to study the morphology of the adrenals. The unilateral
      or bilateral type of aldosterone secretion is based on the realization of an
      adrenal venous sampling. When the hypersecretion is unilateral, the treatment
      consists of adrenalectomy leading to cure of hypertension in 42% of cases,
      improvement in 40% of cases. For patient with bilateral disease or who don't want
      to undergo surgery, treatment is based on spironolactone usually at doses of 25
      or 50 mg in combination with other antihypertensives drugs such as diuretics or
      calcium channel blockers.

PMID- 26298908
TI  - [Renal artery stenosis].
AB  - Renal artery stenosis (RAS) is found in 1 to 2% of all hypertensive patients. Its
      diagnosis involves as a first step Doppler ultrasound and as a confirmatory test,
      CT scan or MRI. When the diagnosis isconfirmed, three questions should be
      addressed by the clinician: 1) the anatomical orm that is, fibromuscular
      dysplasia (FD) or atherosclerotic RAS (ARAS); 2) the potential relation between
      RAS and hypertension with major differences according to the two main etiologies;
      in the presence of FD hypertension is a priorir elated to the stenosis while it
      is not the case with ARAS; 3) is there an indication for revascularization with
      again two opposite situations. Renal angioplasty may cure up to one third of
      patients with FD and improve blood pressure control in some others and has thus
      to be discussed in this clinical context. On the contrary, several randomized
      trials have shown that the blood pressure benefit of renal revascularization is
      limited if any in ARAS and, above all, not associated with an improvement of
      cardiovascular and renal outcomes. Renal angioplasty should thus be restricted to
      highly selected patients while in all cases, cardiovascular prevention should be
      intensified, based on renin angiotensin system blockers, statins, and aspirin
      use. Whatever the management, these patients should be followed both on the renal
      side to detect restenosis or renal impairment, and on other cardiovascular
      complications particularly in the presence of ARAS.

PMID- 26298909
TI  - [Pheochromocytoma and paraganglioma].
AB  - Pheochromocytoma and functional paraganglioma (PH/PGL) are classical causes of
      secondary hypertension. The clinical practice guidelines for PH/PGL have been
      changed by the recent identification of a dozen of susceptibility genes. PH/PGL
      is the neuroendocrine tumor most affected by genetics. Total metanephrin should
      be measured in every young patient suffering of a resistant hypertension. The
      diagnosis is based on conventional imaging assciated with nuclear imaging.
      Genetic testing should be offered to every patient diagnosed for PH/PGL because
      the identification of a germline mutation, which is found in over 30% of the
      cases, will change his work-up and follow-up as well as offer the opportunity of
      a familial genetic testing in relatives. A specialized management is indicated,
      especially for patients with hereditary or metastatic PH/PGL, and should be
      performed in an expert center with a multidisciplinary team.

PMID- 26298910
TI  - [Hypertension during obstructive sleep apnea syndrome].
AB  - Hypertension (HT) related to obstructive sleep apnea syndrome (OSAS) is one of
      the secondary forms of HT. It must be systematically evoked in hypertensive
      patient because the association "obesity, major snoring and excessive diurnal
      sleepiness" is fickle during OSAS. HT in apneic patient is more often diastolic,
      nocturnal, with a non-dipper profile. Moreover, OSAS is very frequently present
      during resistant hypertension. There are many mechanisms linking OSAS to HT. The
      main stimulus is intermittent hypoxia and the most important pathophysiological
      consequence is high sympathetic activity. After doing the diagnosis of OSAS, its
      treatment principally associated lifestyle changes with continuous positive
      airway pressure (CPAP). CPAP can significantly decrease blood pressure,
      especially if compliance to treatment is good and hypertension is resistant.

PMID- 26298911
TI  - [Means and strategy diagnosis of hypertension in the child].

PMID- 26298912
TI  - [Arterial hypertension of renal origin].

PMID- 26298913
TI  - [An evidence based center for primary care].

PMID- 26298914
TI  - [Prevention of breastfeeding complications].

PMID- 26298915
TI  - [Why and how to undertake a conservative treatment of catheter related
      infections].

PMID- 26298916
TI  - [Realities of alcohol withdrawal].

PMID- 26298917
TI  - [Breastfeeding].

PMID- 26298918
TI  - [Monitoring and complications of venous access].

PMID- 26298919
TI  - [Addiction to alcohol].

PMID- 26298920
TI  - [Chronic lymphocytic leukemia].

PMID- 26298921
TI  - [Prevention of fetal risks. Infection, drugs, toxins, radiation].

PMID- 26298922
TI  - Title IX: Implications for Health Care Providers.

PMID- 26298923
TI  - Contemporary Approach To Diagnosis, Management, And Treatment of Varicocele In
      the Adolescent.
AB  - Varicocele is the most common inguinoscrotal pathology among adolescents. It is
      of concern due to the potential effect on fertility. A review of the literature
      focusing on current guidelines regarding diagnosis, evaluation, and management of
      adolescent varicocele was conducted. An algorithm is provided as one method for
      approaching the adolescent varicocele.

PMID- 26298924
TI  - Current and Future Applications Of Genetic Prostate Cancer Screening in the
      Urologic Clinic.
AB  - The limitations of PSA and DRE screening for prostate cancer have prompted much
      research into genetic-based screenings. This survey of innovations and obstacles
      in genomic testing will help prepare urologic clinicians for future
      interventions.

PMID- 26298925
TI  - A Comparison of Affected Individual and Support Person Responses on the Impact of
      Urinary Incontinence on Quality of Life.
AB  - The purpose of this pilot study conducted in Canada was to examine affected
      individual and support person agreement on the impact of urinary incontinence on
      affected individuals' quality of life. Findings suggest that support persons may
      be able to make reasonably accurate inferences regarding the quality of life of
      individuals affected by urinary incontinence.

PMID- 26298926
TI  - Cost Analysis of Adult Male Circumcision with the PrePex Device versus Surgery in
      Rwanda.
AB  - In this study from Rwanda, voluntary adult male circumcision costs 33% less with
      trained nurses using the PrePex device compared with physician-nurse teams
      performing dorsal-slit surgery. These cost savings and the documented safety,
      speed, and efficacy of the PrePex procedure, serve Rwanda's HIV prevention
      program.

PMID- 26298927
TI  - Two Sessions of Behavioral Urotherapy for Bowel and Bladder Dysfunction: Does It
      Get Any Better?
AB  - This study sets to determine the optimal duration of behavioral urotherapy
      necessary to achieve maximal improvement in the management of pediatric bowel and
      bladder dysfunction.

PMID- 26298928
TI  - Student Nurse Understanding Of the Psychosocial Impact Of Urinary Incontinence.
AB  - This study examined the attitudes of baccalaureate student nurses regarding the
      care of the incontinent patient and to explore their beliefs of the psychosocial
      impact urinary incontinence has on the affected adult patient. It explored the
      beliefs and attitudes of traditional-aged student nurses compared to those of:
      older, non-traditional students. Students have a more positive attitude when
      caring for patients who have urinary incontinence yet have a moderate level of
      understanding regarding the associated psychosocial sequela. The benefit of this
      research is that it gives insight into how student nurses perceive incontinent
      patients' feelings and concerns, and refines the current understanding of how
      important students believe it is to deal with a patient's incontinence.

PMID- 26298929
TI  - Time to Invest in the Future.

PMID- 26298930
TI  - Pelvic Floor Dysfunction and Associated Lower Urinary Tract Symptoms--A Case
      Study.
AB  - Lower urinary tract symptoms are a common complaint for women who present with a
      myriad of symptoms. A thorough history and physical examination, as well as
      specific diagnostic testing, can help determine the underlying cause and direct
      the best treatment option as presented in this case study.

PMID- 26298931
TI  - Urological Implications Of Falls in the Elderly: Lower Urinary Tract Symptoms And
      Alpha-Blocker Medications.
AB  - Falls are a leading cause of morbidity and mortality in the elderly. In
      prospective studies, lower urinary tract symptoms (LUTS) have been shown to be an
      independent risk factor for falls. Alpha-blockers, frequently used to treat LUTS
      and benign prostatic hyperplasia, can increase the risk of falls in the elderly
      due to their class effect of orthostatic hypotension. In the urology setting,
      risk factors for falls may be addressed through evaluation and counseling, and by
      careful selection and monitoring of medications for LUTS.

PMID- 26298932
TI  - Pre-Operative Pelvic Floor Muscle Training--A Review.
AB  - The use of pelvic floor muscle training has been well established for the
      management of post-prostatectomy incontinence. In recent years, it has been
      hypothesized that because the severity and period of incontinence are not
      predictable pre-operatively, it makes sense to teach all men the new motor skill
      of correct pelvic floor muscle activation before surgery. This review is based on
      literature found through computerized and manual searches on available databases.
      Included were any studies that looked at the effect of adding pelvic floor muscle
      training pre-operatively and comparing them to the effect of not having pre
      operative pelvic floor muscle exercises. Pre-operative pelvic floor muscle
      training was found to be effective in reducing the time to continence as well as
      the severity of incontinence in only four studies. Adding biofeedback or
      electrical stimulation was not found to change the outcomes.

PMID- 26298933
TI  - An Evidence-Based Approach To the Prevention of Catheter-Associated Urinary Tract
      Infections.
AB  - This article describes a bundle of interventions that effectively reduced the
      incidence of catheter-associated urinary tract infections on the Acute Care
      Medicine' Unit, a general medicine/telemetry unit. A series of evidence-based
      interventions were implemented in October 2011, and since the implementation of
      these interventions, the 28-bed unit has seen a significant reduction in catheter
      associated urinary tract infections.

PMID- 26298934
TI  - The Effect of Intensive Education On Urinary Incontinence Following Radical
      Prostatectomy: A Randomized Control Trial.
AB  - Intense bladder control education failed to improve bladder control among
      patients who underwent a radical prostatectomy as treatment of their prostate
      cancer. Despite this educational intervention, participants continued to
      experience post-operative bladder control problems. Nurses need to develop and
      implement novel interventions that might enhance bladder control.

PMID- 26298936
TI  - Starting the Conversation.

PMID- 26298935
TI  - Web-Based Treatment for Women With Stress Urinary Incontinence.
AB  - This was a non-experimental, descriptive, correlational study designed to assess
      the feasibility and efficacy of an evidence-based online pelvic floor treatment
      program targeting stress urinary incontinence in adult women. The majority of the
      participants reported some level of improvement in their incontinence symptoms
      and overwhelmingly supported the web-based physical therapy program.

PMID- 26298937
TI  - Appraising the Literature On Bathing Practices And Catheter-Associated Urinary
      Tract Infection Prevention.
AB  - As pressure for reduced catheter-associated urinary tract infection (CA UTI)
      rates continues, health care organizations are challenged to find new methods for
      infection prevention. The purpose of this review is to synthesize the evidence
      regarding the impact of bathing practices, particularly non-basin bathing, on
      CAUTI prevention.

PMID- 26298938
TI  - Probiotics in Preventing Recurrent Urinary Tract Infections in Women: A
      Literature Review.
AB  - Increasing antibiotic resistance and increasing resistance to commonly used
      antibiotics makes treatment and prevention of urinary tract infections difficult.
      Although more research is needed, probiotics should be considered a useful and
      safe alternative to antibiotics.

PMID- 26298939
TI  - Refining a Prostate Cancer Survivor's Toolkit.
AB  - Men who have undergone radical prostatectomy for the treatment of prostate cancer
      often lack knowledge about post-surgical care to bridge this gap in knowledge.
      Thus, we developed, refined, and validated a prostate cancer survivor's toolkit,
      which provides these men in the care required after this procedure.

PMID- 26298940
TI  - Application to the Evidence Base: Refining a Prostate Cancer Survivor's Toolkit.

PMID- 26298942
TI  - Ethical Issues in the Disruptive Behaviors of Incivility, Bullying, And
      Horizontal/Lateral Violence.

PMID- 26298941
TI  - Advances in Female Urology: A Review of the 2013 Literature.
AB  - The field of female urology covers a broad spectrum of lower urinary tract
      dysfunction and pelvic disorders. The aim of this article is to provide a
      comprehensive review of the most significant literature published during 2013.

PMID- 26298943
TI  - Professional Apathy: Avoiding And Preventing This Chronic Work Condition.

PMID- 26298944
TI  - The Price of Prior Authorization.

PMID- 26298945
TI  - Underlying Mechanisms and Optimal Treatment for Interstitial Cystitis: A Brief
      Overview.
AB  - The intention of this article is to present a brief overview of the etiology,
      diagnosis, and treatment modalities of interstitial cystitis for primary care
      clinicians. While very succinct, it encapsulates the condition with clear and
      precise definition.

PMID- 26298946
TI  - Undescended Testes: A Clinical and Surgical Review.
AB  - Undescended testes are a common congenital disorder with potential sequelae that
      include infertility and malignancy. This article addresses a contemporary
      perspective on the pathophysiology of the undescended testis, impact on
      testicular function and risk of testicular cancer. Surgical management and
      current guidelines regarding optimal timing of surgery will also be presented.

PMID- 26298947
TI  - A Web-Based Self-Management Intervention for Intermittent Catheter Users.
AB  - A new Web-based self-management intervention was developed for persons with
      spinal cord injury who use intermittent urinary catheters. Included are a
      description of the components, examples from the educational book, and multiple
      screen shots of the online urinary diary.

PMID- 26298948
TI  - Pre- and Post-Operative Care With Associated Intra-Operative Techniques for
      Phalloplasty In Female-to-Male Patients.
AB  - Phalloplasty, or creation of the penis, is one of the steps in gender confirming
      surgery for a female-to-male patient and for males with absence or malformation
      of the penis. Here, the most common techniques for phalloplasty, along with the
      pre-operative and post-operative care are discussed.

PMID- 26298949
TI  - Human Papillomavirus: Not Just a Woman's Concern.
AB  - Human papillomavirus (HPV) association to cervical cancer in women is well
      publicized. It is also linked to serious sequela in males. This article provides
      peer-reviewed information regarding HPV and its relevance to males.

PMID- 26298950
TI  - The Pursuit of Happiness, Science, And Effective Staffing: The Leader's
      Challenge.
AB  - It should be intuitive that happy people produce better results than unhappy
      people. It should be intuitive that leaders must be singularly focused on how
      they can create happiness within their companies so that people can grow and
      thrive and reach sustainable organizational goals. But in spite of such common
      sense, the data show us people are not too happy at work and it is not getting
      better. Health care has much to learn about creating happi ness that in turn
      creates a positive return on investment financially, as well as on patient
      outcomes and the well-being, growth, and productivity of the staff. (1) We need a
      serious call to action in health care that will implement the research about
      happy organizations and their success. Our stakes are high; we must do no harm.

PMID- 26298951
TI  - Clinical Economics. Alzheimer's Disease.

PMID- 26298952
TI  - Health 'care': An examination on the art of caring.

PMID- 26298953
TI  - PRACTICE INNOVATORS Unique ways to thrive--and how you can too.

PMID- 26298954
TI  - Building for success. Lessons from an urgent care entrepreneur.

PMID- 26298955
TI  - Prescribing mobile apps: What to consider.

PMID- 26298957
TI  - Narrowing networks.

PMID- 26298956
TI  - Diversifying your practice.

PMID- 26298958
TI  - PRIMARY CARE PHYSICIANS SAY MOC DOES NOT MAKE THEM MORE EFFECTIVE.

PMID- 26298959
TI  - Clinical Economics. Depression.

PMID- 26298960
TI  - A phone call to remember.

PMID- 26298961
TI  - MEDICARE AT 50 IS IT WORKING?

PMID- 26298962
TI  - Accounts receivable. Strategies for better management. From eligibility
      verification to patient engagement, managing accounts receivable is a vital
      process to maintaining financial health.

PMID- 26298963
TI  - STARTING AN URGENT CARE CENTER. 5 ESSENTIALS FOR SUCCESS.

PMID- 26298964
TI  - After SGR: Physician pay facing a value-driven future. While many details remain
      to be finalized, here's what physicians need to know about the future of Medicare
      reimbursement.

PMID- 26298965
TI  - How Congress finally killed SGR.

PMID- 26298966
TI  - POLLS. MAJORITY OF AMERICANS SUPPORT ACA SUBSIDIES.

PMID- 26298967
TI  - Clinical Economics. Hypertension.

PMID- 26298968
TI  - An early death.

PMID- 26298969
TI  - The lCD-10 transition. Avoiding revenue disruptions.

PMID- 26298970
TI  - EHRs' BROKEN PROMISE. What must be done to win back your trust.

PMID- 26298971
TI  - RISK MANAGEMENT STRATEGIES FOR PATIENT PORTAL USE.

PMID- 26298972
TI  - Improving continuity of care. Bringing physicians together to collaborate on
      patient care requires new ways of thinking.

PMID- 26298973
TI  - STRATEGIES TO MANAGE THE CLAIM DENIAL PROCESS.

PMID- 26298974
TI  - CMS RELEASES MEDICARE PART D PHYSICIAN PRESCRIBING DATA.

PMID- 26298975
TI  - The difficult patient.

PMID- 26298976
TI  - Clinical Economics. Atrial Fibrillation.

PMID- 26298977
TI  - MOC. Doctors strike back.

PMID- 26298978
TI  - Leveraging the front office. Strategies to increase your practice's cash flow.

PMID- 26298979
TI  - Proper use of Modifer 59. UNDERSTANDING THE NEW SUB-CODES.

PMID- 26298980
TI  - PATIENT PORTALS. Essential, but underused by physicians.

PMID- 26298981
TI  - CHOOSING INDEPENDENCE. Tips on moving to private practice.

PMID- 26298982
TI  - THE ABCs OF BETTER MEDICAL PRACTICE MANAGEMENT.

PMID- 26298983
TI  - STUDY PROBES AFFORDABLE CARE ACT IMPACT ON PRIMARY CARE VISITS.

PMID- 26298984
TI  - Clinical Economics Type 2 Diabetes.

PMID- 26298985
TI  - From the other side.

PMID- 26298987
TI  - Dealing with Dr Google. Why communication is key.

PMID- 26298986
TI  - YOUR BEST MALPRACTICE DEFENSES. Reduce risk with a patient-first approach.

PMID- 26298988
TI  - TALKING TREATMENT COSTS. Navigating financial discussions with patients.
      Exploring how the rising of healthcare affects the physician-patient
      relationship.

PMID- 26298989
TI  - GETTING PAID. STRATEGIES & BEST PRACTICES.

PMID- 26298990
TI  - The ethics of researching patients on the web.

PMID- 26298991
TI  - NEW PAYMENT MODELS BRINGING CHANGES TO MEDICAL PRACTICES.

PMID- 26298992
TI  - To care always.

PMID- 26298994
TI  - High-value care STRATEGIES. Guiding patient conversations to optimize care,
      reduce costs.

PMID- 26298993
TI  - Clinical Economics Allergic Rhinitis.

PMID- 26298995
TI  - Managing conflict with patients. Effective communication is vital to managing
      disagreements with patients to resolve tension and prevent negative outcomes.

PMID- 26298996
TI  - AVOIDING SELF-REFERRAL: UNDERSTANDING THE STARK LAWS.

PMID- 26298997
TI  - How to get started with Direct messaging. Many physicians don't use or are
      unaware of Direct secure messaging, but it can help improve care coordination-
      provided you can navigate its challenges..

PMID- 26298998
TI  - IPAs: Joining forces to retain independence. Independent physician associations
      can help doctors meet the business challenges of independent practice, but do
      your homework before joining.

PMID- 26298999
TI  - BUSINESS INSURANCE COVERAGE EVERY PHYSICIAN SHOULD HAVE.

PMID- 26299000
TI  - AFFORDABLE CARE ACT WILL COST BILLIONS LESS THAN PREDICTED.

PMID- 26299001
TI  - Cinical Economics Obesity.

PMID- 26299002
TI  - ICD-10 DOCUMENTATION. The key to getting paid.

PMID- 26299003
TI  - CAREER DECISIONS: SHOULD YOU START, BUY OR JOIN A PRACTICE?

PMID- 26299004
TI  - Preventing payer denials, A physician's roadmap to performance improvement must
      include best practices to reduce and reverse unpaid claims.

PMID- 26299005
TI  - Physician liability for the actions of midlevel providers.

PMID- 26299006
TI  - MALPRACTICE INSURANCE CONSIDERATIONS FOR EMPLOYED PHYSICIANS.

PMID- 26299007
TI  - Treating Medicaid patients. Medicaid is a difficult payer to work with, but
      growing patient numbers means physicians must consider how to overcome the
      obstacles.

PMID- 26299008
TI  - CONGRESS SEEKS TO AID PHYSICIANS ON THE BURDEN OF MEANINGFUL USE 2.

PMID- 26299009
TI  - MU2: Mission Impossible. Ill-conceived government mandate places unnecessary
      burden on physicians.

PMID- 26299010
TI  - Automated precertification lags behind, but new solutions emerging.

PMID- 26299011
TI  - EMBRACING EHRs: 8 WAYS THEY CAN IMPROVE YOUR PRACTICE.

PMID- 26299012
TI  - Engaging patients to decrease costs and improve outcomes.

PMID- 26299013
TI  - Creating and maintaining an employee benefits package.

PMID- 26299014
TI  - CODING QUESTIONS ANSWERED: MIDLEVEL BILLING, WAIVING COPAYS AND MORE.

PMID- 26299015
TI  - Building a medical group in 12 steps.

PMID- 26299016
TI  - HIPAA LIABILITY PROTECTIONS: BUSINESS ASSOCIATE AGREEMENTS.

PMID- 26299017
TI  - How motivational interviewing can help reach noncompliant patients.

PMID- 26299018
TI  - MEDICAID PROVIDER FIGURES DON'T REFLECT REALITY OF PATIENT CARE.

PMID- 26299019
TI  - PAYMENT OUTLOOK FOR 2015. Your guide to solutions to help your practice thrive.

PMID- 26299020
TI  - STRATEGIES FOR PROACTIVE PAYER CONTRACT NEGOTIATIONS.

PMID- 26299021
TI  - Electronic prior authorization. The solution to physicians' headaches?.

PMID- 26299022
TI  - Streamlining your practice.

PMID- 26299023
TI  - PREPARING FOR 2015 EVALUATION AND MANAGEMENT CODE CHANGES.

PMID- 26299024
TI  - THE IMPORTANCE OF IN-PERSON STAFF MEETINGS.

PMID- 26299025
TI  - HOW AN EMPLOYEE MANUAL CAN HELP CONTROL RISK AND CONTAIN COST.

PMID- 26299026
TI  - The defensive medicine balancing act.

PMID- 26299027
TI  - STUDY: REFERRAL PROCESS NEEDS PROTOCOLS, STANDARDIZATION.

PMID- 26299028
TI  - Jeremy.

PMID- 26299029
TI  - Clinical Economics. Insomnia.

PMID- 26299030
TI  - Chronic Care Management SUCCESS. How to overcome tech limitations.

PMID- 26299031
TI  - Mining EHR data for quality improvement. How physicians can provide better care
      and adhere to quality metrics, and why its important to start now.

PMID- 26299032
TI  - STRATEGIES TO OPTIMIZE YOUR USE OF ELECTRONIC HEALTH RECORDS.

PMID- 26299033
TI  - CONSIDERATIONS WHEN REMOVING A PATIENT FROM YOUR PRACTICE.

PMID- 26299034
TI  - PILOT PROGRAM WILL EXPLORE GIVING PATIENT ACCESS TO EHR RECORDS.

PMID- 26299035
TI  - Clinical Economics. Asthma.

PMID- 26299036
TI  - FROM QUANTITY? TO QUALITY. Meeting the new demands of value-based care.

PMID- 26299037
TI  - YOU'VE BEEN SUED FOR MALPRACTICE--NOW WHAT?

PMID- 26299038
TI  - The rising cost of generic drugs.

PMID- 26299039
TI  - In our patients' shoes. Reducing barriers to care in diabetes treatment.

PMID- 26299040
TI  - The revenue cycle decision.

PMID- 26299041
TI  - WHAT YOU NEED TO KNOW ABOUT CHRONIC CARE MANAGEMENT.

PMID- 26299042
TI  - Defend your practice against HIPAA violations.

PMID- 26299043
TI  - 'WE GOT IT WRONG': ABIM DOES ABOUT-FACE ON RECENT MOC CHANGES.

PMID- 26299044
TI  - MAKING A CRUCIAL DECISION FOR YOUR PRACTICE. ACO-PCMH.

PMID- 26299045
TI  - Becoming a PCMH. 4 transformations to consider.

PMID- 26299046
TI  - Specialty ACOs. What physicians need to know.

PMID- 26299047
TI  - High deductibles. Why physicians must adjust how they practice.

PMID- 26299048
TI  - GETTING PAID FOR WOMEN'S HEALTH SERVICES IN PRIMARY CARE.

PMID- 26299049
TI  - HOW YOUNG PHYSICIANS CAN MASTER LEADERSHIP ROLES.

PMID- 26299050
TI  - Why empathy may be the best risk management strategy.

PMID- 26299051
TI  - NEW STUDIES FUEL CONTROVERSY OVER MAINTENANCE OF CERTIFICATION.

PMID- 26299052
TI  - [The neuromatrix and its importance in pain neurobiology].
AB  - The gate control theory of pain, introduced by Melzack and Wall in 1965, led the
      way in pain research during the second half of the 20th century. Eventually, the
      observation of pain-related phenomena which the theory could not satisfactorily
      explain propelled Melzack to develop a new concept, the neuromatrix, which
      considers as participants in the pain transmission and modulation system, certain
      brain areas not traditionally associated with the pain experience. This concept
      places equal importance on the sensory, affective and cognitive aspects of pain,
      helping the advancement of novel diagnostic and therapeutic approaches in
      different clinical pain conditions.

PMID- 26299053
TI  - [Serological diagnosis of sporotrichosis using an antigen of Sporothrix schenckii
      sensu stricto mycelium].
AB  - We developed and analyzed an Enzyme-Linked Immunosorbent Assay (ELISA) in order
      to detect antibodies in sera from sporotrichosis patients. We used a crude
      antigen of Sporothrix schenckii sensu stricto, obtained from the mycelial phase
      of the fungi. Positive sera were analyzed by other serological techniques such as
      double immunodiffusion (IGG) and counterimmunoelectrophoresis (CIE). The assay
      was validated by using sera from patients with other pathologies such as:
      histoplasmosis, paracoccidioidomycosis, tuberculosis, leishmaniasis, lupus and
      healthy individuals as negative controls. For the Sporothrix schenckii sensu
      stricto antigen, we found a 100% of specificity by every technique and
      sensitivity higher than 98% with IDD, CIE and ELISA. Our results show a high
      sensitivity and specificity for the Sporothrix schenckii sensu stricto antigen,
      so it can be used for IDD, CIE and ELISA. The results suggest that this antigen
      could be used in conjunction with other conventional tests for differential
      diagnosis and may be useful for monitoring the disease progression and response
      to treatment.

PMID- 26299054
TI  - [Effects of occupational exposure to pesticides on semen quality of workers in an
      agricultural community of Merida state, Venezuela].
AB  - Numerous studies report adverse effects of pesticides on male reproductive
      health. The objectives of this study were to investigate whether there is a
      relationship between occupational exposure to pesticides and semen quality, and
      to determine whether chronic exposure to pesticides differentially affects semen
      quality in men of different ages. A comparative study of 64 farmers and 64
      control men was performed. The farmers were interviewed to determine their
      occupational history and particularly, activities that may involve exposure to
      pesticides. Semen parameters were evaluated and a comparative analysis of semen
      variables between exposed and control groups, as well as between age groups: 18
      29, 30-37 and 38-60 years was done. Significant alterations of some semen
      parameters in the exposed group were found, such as: decreases in sperm
      concentration, slow progressive motility and sperm membrane integrity; at the
      same time, increases in eosin Y positive and sperm DNA fragmentation index. The
      results obtained by age groups showed significant differences between exposed and
      control groups for the parameters of membrane integrity, eosin Y positive and
      sperm DNA fragmentation index, being the exposed group between 18-29 years that
      showed the highest altered cases of these parameters. Our results prove that
      occupational pesticide exposure is associated with alterations in sperm quality,
      creating a risk to farm workers in their reproductive capacity.

PMID- 26299055
TI  - [Novel central dopaminergic agents derived from atypical di-substituted 2
      aminoindane-4, 7. Synthesis and central pharmacological profile].
AB  - In recent decades, many compounds with central dopaminergic activity have been
      designed, synthesized and evaluated pharmacologically. However, it has not been
      possible to obtain a drug able to improve or cure diseases involving dopaminergic
      regulation in the central nervous system, such as Parkinson's disease and
      schizophrenia, among others. Taking into consideration the term "atypical
      pharmacophore" and from the compound 5, the aralkyl fragment was incorporated,
      and the compounds 10, 11, 13a-h and 14a-h were synthesized. Both the compounds 10
      and 13a-h under its methoxylated form and the compounds 11 and 14a-h under the
      phenolic form, were evaluated to determine their pharmacologically agonistic and
      antagonistic effects on central dopaminergic activity. For this, the effect of
      intracerebroventricular injection of said compounds on the hydromineral balance
      and stereotyped behavior in rats, was determined. The results of the preliminary
      pharmacological evaluation show a centrally acting action through dopamine
      mechanisms, in which the compounds 10, 11, 13d-h and 14a showed responses as
      agonists, whereas compounds 14b-h, had responses as antagonists.

PMID- 26299056
TI  - [Cadherins E and P expression in the molecular types of breast cancer].
AB  - The epithelial-mesenchymal transition is a process by which tumor cells lose
      their epithelial markers and migrate to distant organs. This process involves
      several cell adhesion proteins such as E-cadherin and P-cadherin. The present
      study was performed in 354 pacients diagnosed with breast infiltrating ductal
      carcinoma in the Oncology Institute "Dr. Miguel Perez Carreno", Valencia,
      Venezuela. The expression of 22 molecules was analyzed by tissue micro-arrays and
      the results were compared with the molecular clases established by
      immunohistochemistry, according to the'expression of estrogen receptor (ER),
      progesterone (PR) and human epidermal growth factor receptor type 2 (HER2), and
      with the overall survival (OS). Based on the results of ER, PR and HER2 molecular
      classes according to the following per- centages were established: Luminal A
      42.4%, Luminal B 20.3%, 9% HER2 and 28.2% triple negative (TN). E-cadherin
      expression was observed conserved in most of the tumors of this series, 92.5% of
      cases. TN phenotype tumors showed a high percentage (41.7%) with absent or
      reduced expression. The P-cadherin was expressed in 40.5% of cases, although
      expressed in all classes; the proportion was significantly higher in cases TN. No
      significant prognostic value was observed when analyzing the overall five-year
      survival of patients with tumors with absent or reduced expression of E-cadherin.
      The P-cadherin expression had a negative relationship with the OS.

PMID- 26299057
TI  - Prevalence of the metabolic syndrome, insulin resistance index, leptin and
      thyroid hormone levels in the general population of Merida (Venezuela).
AB  - The metabolic syndrome (MetSyn) is a significant risk factor for cardiovascular
      events, but scarce information exists about its frequency in Venezuela. In this
      cross-sectional study, we quantified the prevalence of the MetSyn in a
      probabilistic, stratified sample of 274 subjects aged > or =18 years from the
      Libertador district in Merida, Venezuela. Secondary outcomes were the measurement
      of thyroid hormones (free T4 and TSH), leptin levels, and insulin resistance
      index (HOMA2-IR). The frequency of MetSyn (percentage +/- 95% confidence
      interval) according to several diagnostic criteria was as follows: National
      Cholesterol Education Panel (NCEP, original): 27.4% (22.1-32.7); modified NCEP:
      31.8% (26.3-37.3); International Diabetes Federation: 40.9% (35.1-46.7); Latin
      American Diabetes Association: 27% (21.7-32.3), and Venezuelan criteria: 31.8%
      (26.3-37.3). The MetSyn was more frequent in males than in females with most
      diagnostic criteria. The estimated prevalence of type 2 diabetes mellitus was
      2.9% either according to the patients' self reports or to fasting glucose level
      found to be above 126 mg/dL. Abnormal HOMA2-IR index, free T4 and TSH (above the
      95th percentile) were detected in 4.5%, 4.4% and 5.1% of the sample,
      respectively. Free T4 and TSH levels below the 5th percentile were detected in
      4.4% and 4.7% of subjects respectively. These values are presented for
      comparisons with forthcoming studies in specific clinical populations. While
      studies are being conducted about the different definitions of the MetSyn in
      Venezuela, we recommend analyzing and publishing local research data with all the
      available criteria so as to allow comparisons with the results already reported
      in the literature.

PMID- 26299058
TI  - KPC and VIM producing Enterobacter cloacae strain from a hospital in northeastern
      Venezuela.
AB  - An 83-year-old male patient is admitted to the central hospital in Cumana,
      Venezuela with severe urinary infection, history of hospitalizaions and prolonged
      antimicrobial treatments. A strain of Enterobacter cloacae was isolated showing
      resistance to multiple types of antibiotics (only sensitive to gentamicin), with
      phenotype of serine- and metallo-carbapenemases. Both, bla(VIM-2) and bla(KPC)
      genes were detected in the isolate. This is the first report of an
      Enterobacteriaceae species producing both KPC carbapenemase and VIM metallo
      carbapenemase in Venezuela. This finding has a great clinical and epidemiological
      impact in the region, because of the feasibility of transferring these genes,
      through mobile elements to other strains of Enterobacter and to other infection
      causing species of bacteria.

PMID- 26299059
TI  - [Neuroprotective mechanisms of cannabinoids in brain ischemia and
      neurodegenerative disorders].
AB  - One of the most important causes of morbidity and mortality is neurologic
      dysfunction; its high incidence has led to an intense research of the mechanisms
      that protect the central nervous system from hypoxia and ischemia. The mayor
      challenge is to block the biochemical events leading to neuronal death. This may
      be achieved by neuroprotective mechanisms that avoid the metabolic and
      immunologic cascades that follow a neurological damage. When it occurs, several
      pathophysiological events develop including cytokine release, oxidative stress
      and excitotoxicity. Neuroprotective effects of cannabinoids to all those
      mechanisms have been reported in animal models of brain ischemia, excitotoxicity,
      brain trauma and neurodegenerative disorders. Some endocannabinoid analogs are
      being tested in clinical studies (I-III phase) for acute disorders involving
      neuronal death (brain trauma and ischemia). The study of the cannabinoid system
      may allow the discovery of effective neuroprotective drugs for the treatment of
      neurological disorders.

PMID- 26299060
TI  - [Pathogenic mechanisms of neuronal damage in multiple sclerosis].
AB  - Multiple sclerosis is the most common cause of progressive neurological
      disability in young adults. This disease involves damage to the myelin sheath
      that normally insulates the electrical activity of nerve fibers. This leads to a
      wide range of symptoms as specific nerves become injured and lose their function.
      Epidemiological and experimental studies show that genetic alterations,
      antioxidant enzyme abnormalities and autoimmunity are risk factors for developing
      the disease. Recent evidence suggests that inflammation and oxidative stress
      within the central nervous system are major causes of ongoing tissue damage.
      Resident central nervous system cells and invading inflammatory cells release
      several reactive oxygen and nitrogen species which cause the histopathological
      features of multiple sclerosis: demyelization and axonal damage. The interplay
      between inflammatory and neurodegenerative processes results in an intermittent
      neurological disturbance followed by progressive accumulation of disability.
      Reductions in inflammation and oxidative stress status are important therapeutic
      strategies to slow or halt the disease processes. Therefore, several drugs are
      currently in trial in clinical practice to target this mechanism; particularly
      the use of supplements such as antioxidants and omega-3 polyunsaturated fatty
      acids, in order to improve the survival and quality of patients' lives.

PMID- 26299061
TI  - [Evidence that suggest the reality of reincarnation].
AB  - Worldwide, children can be found who reported that they have memories of a
      previous life. More than 2,500 cases have been studied and their specifications
      have been published and preserved in the archives of the Division of Perceptual
      Studies at the University of Virginia (United States). Many of those children
      come from countries where the majority of the inhabitants believe in
      reincarnation, but others come from countries with different cultures and
      religions that reject it. In many cases, the revelations of the children have
      been verified and have corresponded to a particular individual, already dead. A
      good number of these children have marks and birth defects corresponding to
      wounds on the body of his previous personality. Many have behaviors related to
      their claims to their former life: phobias, philias, and attachments. Others seem
      to recognize people and places of his supposed previous life, and some of their
      assertions have been made under controlled conditions. The hypothesis of
      reincarnation is controversial. We can never say that it does not occur, or will
      obtain conclusive evidence that it happens. The cases that have been described so
      far, isolated or combined, do not provide irrefutable proof of reincarnation, but
      they supply evidence that suggest its reality.

PMID- 26299062
TI  - Performance Evaluation of the Sysmex CS-5100 Automated Coagulation Analyzer.
AB  - BACKGROUND: Coagulation testing is widely applied clinically, and laboratories
      increasingly demand automated coagulation analyzers with short turn-around times
      and high-throughput. The purpose of this study was to evaluate the performance of
      the Sysmex CS-5100 automated coagulation analyzer for routine use in a clinical
      laboratory. METHODS: The prothrombin time (PT), international normalized ratio
      (INR), activated partial thromboplastin time (APTT), fibrinogen (Fbg), and D
      dimer were compared between the Sysmex CS-5100 and Sysmex CA-7000 analyzers, and
      the imprecision, comparison, throughput, STAT function, and performance for
      abnormal samples were measured in each. RESULTS: The within-run and between-run
      coefficients of variation (CV) for the PT, APTT, INR, and D-dimer analyses showed
      excellent results both in the normal and pathologic ranges. The correlation
      coefficients between the Sysmex CS-5100 and Sysmex CA-7000 were highly
      correlated. The throughput of the Sysmex CS-5100 was faster than that of the
      Sysmex CA-7000. There was no interference at all by total bilirubin
      concentrations and triglyceride concentrations in the Sysmex CS-5100 analyzer.
      CONCLUSIONS: We demonstrated that the Sysmex CS-5100 performs with satisfactory
      imprecision and is well suited for coagulation analysis in laboratories
      processing large sample numbers and icteric and lipemic samples.

PMID- 26299063
TI  - Circulating Cell Free Mitochondrial DNA is a Biomarker in the Development of
      Coronary Heart Disease in the Patients with Type 2 Diabetes.
AB  - BACKGROUND: Circulating cell-free mtDNA (ccf-mtDNA) is presumably derived from
      injured tissue or cells in the body and has been suggested to be a potential
      biomarker in several diseases. In the present study, we investigated whether ccf
      mtDNA levels could serve as a biomarker of diabetic patients without Coronary
      Heart Disease (CHD) and correlate with their incidence to develop CHD. METHODS:
      Ccf-mtDNA levels in plasma and the traditional CHD risk factors were determined
      in 50 type 2 diabetes (DM) with CHD and 50 DM without CHD patients and 50 age-
      and sex-matched healthy controls. MtDNA levels were assessed by measuring the
      NADH dehydrogenase 1 gene using quantitative real-time PCR. ROC curve analyses of
      plasma mtDNA in DM with or without CHD were also determined. Multivariate
      logistic regression analyses were conducted to determine the correlation between
      the mtDNA levels and traditional CHD risk factors. RESULTS: The plasma ccf-mtDNA
      levels and CRP were significantly elevated in DM compared with healthy controls,
      and a consistent increase of mtDNA in diabetes with CHD compared to those without
      CHD. The area under the ROC curves of mtDNA in DM patients versus DM patients
      with CHD and healthy controls was 0.843 and 0.898, respectively. Correlation
      analyses showed that the mtDNA levels were significantly correlated with that of
      C-reactive protein (CRP) in patients with CHD. CONCLUSIONS: Ccf-mtDNA was
      elevated in type 2 diabetes with CHD and correlated with CRP levels. Both may be
      considered a prognostic biomarker of CHD development.

PMID- 26299064
TI  - Differentiation Borrelia Species in Environmental Samples with High-Resolution
      DNA Melting Analysis.
AB  - BACKGROUND: Borrelia burgdorferi sensu lato includes at least 20 species in the
      world, and half of these are found in Europe. The usefulness of high resolution
      melting (HRM) analysis of DNA denaturation curves has been assessed for
      differentiation of Borrelia species. METHODS: HRM protocol for Borrelia species
      was used to examine the 77 DNA extracts selected from earlier studies with the
      use of three different molecular markers: flaB, rplL, and groEL. RESULTS: The
      studies revealed that the best marker is the groEL gene, which enables
      identification of 8 Borrelia species, including B. miyamotoi from the relapsing
      fever borreliae group and 7 of B. burgdorferi s.l. complex (B. garinii, B,
      afzelii, B. burgdorferi s.s., B. valaisiana, B. lusitaniae, B. bissetii, B.
      spielmanii). CONCLUSIONS: The HRM method, when compared with other PCR variants
      with regard to the reduced time of analysis, is an alternative for the procedures
      used in the molecular diagnostics of borreliosis including testing of blood
      samples or saved Ixodes ticks for the presence and genotyping of Borrelia
      burgdorferi after biting a patient.

PMID- 26299065
TI  - Albuminuria and Glomerular Filtration in Patients with Essential Hypertension.
AB  - BACKGROUND: Essential hypertension (EH) is a widespread disease. One frequent
      complication of EH is Chronic Kidney Disease (CKD), whose diagnosis is delayed
      due to its asymptomatic course. The purpose of this study is to determine the
      involvement of the kidneys in patients with EH by biomarkers for kidney damage
      (albuminuria) and glomerular filtration rate (GFR) with creatinine and cystatin
      C. METHODS: We observed a control group of 153 healthy volunteers and a group of
      150 patients with EH. The biomarkers we tested were urinary albumin, ACR, total
      protein, and PCR. The GFR was calculated by the CKD-EPI formula using creatinine
      simultaneously and by the combined formula CKD-EPI using creatinine and cystatin
      C. RESULTS: The obtained results for the studied biomarkers in the control group
      are similar to the ones reported in the literature. In the group of patients with
      EH (at the time of study none of which had been diagnosed with CKD) we observed
      albuminuria A2 in 59 of the patients (39.9%) and none with albuminuria A3;
      increased ACR in 60 patients (40%); PCR above reference range in 42 patients
      (28%). GFRR was < 60 mL/min/1.73 m2 in 13 patients (8.6%). CONCLUSIONS: These
      results show that albuminuria A2 and ACR are sensitive, while GFR is a specific
      biomarker for kidney damage. For patients with EH, a timely follow-up of these
      biomarkers is necessary in order to decrease the progression of the kidney damage
      to Chronic Kidney Failure, cardiac complications, and premature mortality.

PMID- 26299066
TI  - Biochemical Identification of Vitamin B12 Deficiency in a Medical Office.
AB  - BACKGROUND: A vitamin B12 deficiency can be an underlying cause or a
      deteriorating factor in several diseases. Nevertheless, early identification of
      such a deficiency remains a problem. Holotranscobalamin (HTC) is presently
      considered to be the gold standard. We tested the predictive power of other B12
      parameters by comparing them with HTC. METHODS: The blood of 77 patients from a
      medical office was tested for HTC, total B12 (CLIA [chemiluminescent immunoassay]
      and MTP [microbiological test with microtitre plates]), MMA (methylmalonic acid),
      HCY (homocysteine), and MCV (mean cell volume). The parameters were correlated
      and sensitivity, specificity, PPV (positive predictive value), NPV (negative
      predictive value), LR+ (positive likelihood ratio), and LR- (negative likelihood
      ratio) in comparison to HTC were determined. A ROC analysis was also performed.
      RESULTS: At a cutoff value of 35 pmol/L for HTC, the total B12 CLIA (cutoff 211
      ng/L) qualified 53% of individuals as having a B12 deficiency. The total B12 MTP
      (cutoff 288 ng/L) classified 71% as having a B12 deficiency. Specificity was
      similar in both cases (CLIA, 93%; MTP, 95%). With a cutoff value of 10 umol/L for
      homocysteine, the best negative prediction was achieved. MVA has a low
      sensitivity (41%) and a high specificity (90%). Based on the ROC analysis, which
      indicated superiority of the B12-MTP, the reference levels of B12-CLIA and B12
      MTP were raised to 304 and 368 ng/L, respectively. Thus, a probable B12
      deficiency was identified in 94% of cases with either method and with a
      comparable specificity. CONCLUSIONS: If total B12 is applied to identify B12
      deficiency, the cutoff values should be elevated to 304 (B12-CLIA) and 368 ng/L
      (B12-MTP) to improve the predictive power. The negative-predictive power of HCY
      can be useful in daily routine. HTC has a broad grey area of uncertainty and MMA
      should only be applied as a confirmatory test.

PMID- 26299067
TI  - Erythropoietin Receptors and IgG Autoantibody Expression on Nucleated
      Erythrocytes in Some Cases of Immuno-Related Pancytopenia.
AB  - BACKGROUND: In recent years, we have detected autoantibodies in bone marrow (BM)
      hemopoietic cells in some patients with idiopathic cytopenia of undetermined
      significance (ICUS), termed immunorelated pancytopenia (IRP). However, we know
      little about the targets of these autoantibodies. METHODS: Twenty-six newly
      diagnosed IRP patients with IgG autoantibody on nucleated erythrocytes and 20
      healthy donors as controls were enrolled in this study. The serum erythropoietin
      (EPO) level was examined by ELISA. Expression of EPO receptor (EPOR) and IgG
      autoantibody on the membrane of nucleated erythrocytes were detected by flow
      cytometry before and after autoantibody stripping. RESULTS: The serum EPO level
      of the untreated patients was 199.9 +/- 106.4 mIU/mL, which was significantly
      higher than that of normal controls (13.2 +/- 8.41 mIU/mL, p < 0.01). EPOR
      expression on nucleated erythrocytes in the patients was 1.38 +/- 0.73%, lower
      than that of normal controls (2.33 +/- 1.73%), but there was no significant
      difference; EPOR in these patients was inversely correlated with IgG autoantibody
      on erythrocytes (r = -0.479, p = 0.013). The regression equation was Y = 0.116
      0.479X; EPOR expression on the membrane increased significiantly (5.63 +/- 4.99%,
      p < 0.01) after stripping the autoantibodies. After immunosuppressive treatment,
      median hemoglobin increased from 72 g/L to 98 g/L, and median reticulocytes
      increased from 1.46% to 3.56%. CONCLUSIONS: IgG autoantibodies might block or
      competitively inhibit EPOR on nucleated erythrocytes in some cases of ICUS.

PMID- 26299068
TI  - Survival and Prognostic Analysis of Primary Nasopharyngeal Carcinoma in North
      China.
AB  - BACKGROUND: To investigate the prognostic factors of Nasopharyngeal Carcinoma
      (NPC). METHODS: Retrospective analysis was carried out on the clinical data
      collected from three hospitals in North China between September, 1999 to March,
      2012. RESULTS: Higher survival rates (1, 3, 5, and 10 year) were found in NPC
      patients who were female, non-smokers, early clinical phase, and T1-2 (p < 0.05).
      No association was found between survival rates and drinking habits, lesion
      location, pathological types, N stages, and radiotherapy pattern. The 1-, 3-, and
      5-year overall survival rates were equal following both conventional radiotherapy
      and Intensity-Modulating Radiotherapy (IMRT). CONCLUSIONS: Patient gender, age,
      smoking status, clinical stages, and T stages all served as prognostic factors of
      nasopharyngeal carcinoma.

PMID- 26299069
TI  - High Prolactin Excretion in Patients with Diabetes Mellitus and Impaired Renal
      Function.
AB  - BACKGROUND: The metabolic clearance of prolactin (PRL) is partially executed by
      the kidney. Here, we investigate the urine excretion of PRL in patients with
      Diabetes Mellitus and renal impairment. METHODS: Serum and urine samples were
      collected from male, mestizo patients in central Mexico employing a cross
      sectional study design. Ninety-eight individuals had either no diabetes and
      normal renal function (control), diabetes and normal renal function, or diabetes
      with impaired renal function. PRL was determined by a chemiluminescent
      immunometric assay; protein, albumin, and creatinine were evaluated using
      quantitative colorimetric assays. The results were analyzed using ANOVA-testing.
      RESULTS: Patients with Diabetes Mellitus and renal impairment had significantly
      higher urine PRL levels than patients with Diabetes Mellitus and normal renal
      function and control patients. Higher urine PRL levels were associated with lower
      glomerular filtration rates, higher serum creatinine, and higher urinary albumin
      to-creatinine ratios (UACR). Urine PRL levels correlated positively with UACR.
      Serum PRL levels were similar among groups. CONCLUSIONS: Patients with Diabetes
      Mellitus and impaired renal function demonstrate a high urinary PRL excretion.
      Urinary PRL excretion in the context of proteinuria could contribute to PRL
      dysregulation in renal impairment.

PMID- 26299070
TI  - Staurosporine Induces Platelet Apoptosis Through p38 Mitogen-Activated Protein
      Kinase Signaling Pathway.
AB  - BACKGROUND: Staurosporine (STS), a microbial alkaloid and potent PKC inhibitor,
      has become one of the most promising anti-cancer drugs. STS effectively induces
      apoptosis in many nucleated cells; however, it is still unclear whether STS
      induces apoptosis in enucleated platelets. METHODS: Apoptotic events in platelets
      treated with STS were assessed by flow cytometry or western blotting. RESULTS:
      STS induced depolarization of mitochondrial inner transmembrane potential
      (DeltaPsim), up-regulation of Bax and Bak, phosphatidylserine (PS) exposure,
      release of mitochondrial cytochrome c, and activation of caspase-8 and caspase-9
      in human platelets. Furthermore, STS stimulation induced phosphorylation of p38
      mitogen-activated protein kinase (MAPK). Inhibition of p38 MAPK activation
      significantly reduced DeltaPsim depolarization and PS exposure in platelets
      stimulated with STS. CONCLUSIONS: These data indicate that STS induces platelet
      apoptosis via the p38 MAPK signaling pathway. These findings suggest that
      platelet apoptosis-related hemorrhage should be noticed in STS and its
      derivatives in clinical tests.

PMID- 26299071
TI  - Evaluation of the Meritas(r) BNP Test for Point-of-Care Testing.
AB  - BACKGROUND: BNP and NT-proBNP are widely used as rule-out tests for heart failure
      (HF) and they are frequently requested by primary care doctors. A point-of-care
      (POC) test would reduce the time to diagnosis for patients with suspected HF. The
      aim of the study was to evaluate a POC BNP test. METHODS: Plasma BNP results
      obtained with the Meritas(r) POC instrument (n = 82) were compared with the
      corresponding plasma BNP results analyzed on an Advia Centaur analyzer (Siemens
      Healthcare, Erlangen, Germany). RESULTS: The two methods showed concordant
      results with a Passing-Bablok correlation between the two methods: BNP(Meritas) =
      1.00 x BNP(Siemens) + 1.09; r = 0.9773. CONCLUSIONS: The study show that the
      Meritas(r) BNP assay could be used in primary care permitting rapid BNP testing
      to rule out heart failure.

PMID- 26299072
TI  - Establishment and Characterization of a CD20-Positive NK/T-Cell Lymphoma Cell
      Line.
AB  - BACKGROUND: CD20 positive NK/T-cell lymphoma is extremely rare and difficult for
      clinical treatment. Due to the lack of an established cell model for this
      disease, less is known about its biological characterization and potential
      therapeutic options. METHODS: A cell line of NK/T-cell lymphoma, which was
      enriched by magnetic sorting with proper cell surface markers (CD56) from
      peripheral blood mononuclear cells (PBMCs) drawn from a 21-year-old male patient
      with nasal angiocentric NK/T-cell lymphoma, was designated as ZQNK-29.
      Immunophenotypic analysis of ZQNK-29 was performed by flow cytometric and
      immunohistochemical analysis. Comparative genomic hybridization (CGH) analysis
      was used for cytogenetic analysis of ZQNK-29. Potential rearrangements of the
      immunoglobulin gene and Epstein-Barr virus (EBV) infection were examined by PCR
      and RT-PCR, respectively. RESULTS: ZQNK-29 cells express the phenotypic T-cell
      marker (CD3), T cell activation markers (HLA-DR), markers for both NK and
      cytotoxic T lymphocytes (TIA-1), and B-lineage marker CD20; however, expression
      of CD56 was not detected in expanded ZQNK-29 cells although this NK cell surface
      marker was used as one of selective cell surface markers for the initial
      isolation of NK/T cells. RT-PCR analysis showed that the pattern of gene
      expressions for infected EBV was latency type III, with the expressions of LMP1,
      EBNA-1, and EBNA-2; no rearrangements were found in the heavy-chain of the
      immunoglobulin gene or in the y chain of the T cell receptors (TCRs) gene. CGH
      analysis demonstrated that ZQNK-29 possessed an abnormal karyotype, 46XY, 1p
      (dist)+, 4p (dist)+, 4q (mid)-, 5q (mid)-, 9q (dist)+, 16p (dist)+, 16q (dist)+,
      17p+, 17q (dist)+, 19q (dist)+, 20p+, 20q+, 21q+, and 22q+. Of these, 1p (dist)+,
      which has been confirmed to be mitochondrial DNA amplification, is believed to be
      mainly caused by EBV infection. CONCLUSIONS: ZQNK-29 is a well characterized
      premature human NK/T-cell lymphoma cell line with expression of the B-cell marker
      CD20 and will provide a useful pre-clinic model for characterization and
      potential therapeutic studies of the aggressive NK/T-cell lymphoma.

PMID- 26299073
TI  - OXA-type Carbapenemases and Susceptibility of Colistin and Tigecycline Among
      Carbapenem-Resistant Acinetobacter Baumannii Isolates from Patients with
      Bacteremia in Turkey.
AB  - BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) has emerged as
      one of the most troublesome pathogens in healthcare settings worldwide. The
      present study was conducted to analyze the genes encoding resistance to
      carbapenems and to determine in vitro activity of colistin and tigecycline
      against CRAB isolates from blood culture of hospitalized patients at Istanbul
      University Cerrahpasa Medical School hospital. METHODS: Between January 2012 and
      June 2014, a total of 72 CRAB isolates were isolated by conventional methods from
      blood cultures of patients with bacteremia who were hospitalized in intensive
      care units and in various departments of the hospital. The isolates were
      confirmed using a Phoenix automated system. Antibiotic susceptibilities were
      determined by disk diffusion method and Etest. Molecular detection of resistance
      genes were screened by multiplex real time polymerase chain reaction (qPCR) and
      PCR parameters. RESULTS: CRAB isolates were highly resistant to tetracycline
      (86.1%), trimethoprim/sulfamethoxazole (84.7%), ceftazidime (83.3%), cefepime
      (81.9%), ciprofloxacin (81.9%), amikacin (75.0%), piperacillin/tazobactam
      (75.0%), cefotaxime (72.2%), and gentamicin (69.4%). Tigecycline and colistin
      resistance were not detected. MIC50 and MIC90 of tigecycline (MIC ranges 0.016-1
      ug/mL) and colistin (MIC ranges 0.125-1.5 ug/mL) were found to be 0.5 ug/mL and 1
      ug/mL, respectively. All isolates were positive for OXA-51 that shows molecular
      identification of A. baumannii. Fifty-one (70.8%) and 2 (2.8%) of these isolates
      were positive for OXA-23 and OXA-58 genes, re- spectively. CONCLUSIONS: This
      study indicated the most of the CRAB isolates in our hospital carry the OXA-23
      gene. Colistin and tigecycline resistance were not detected. However, significant
      effort must be done to prevent the spread of OXA-23-producing CRAB-isolates and
      continuous monitoring of drug resistance is necessary in clinical settings.

PMID- 26299074
TI  - Molecular Characterization of KRAS, BRAF, and EGFR Genes in Cases with Prostatic
      Adenocarcinoma; Reporting Bioinformatics Description and Recurrent Mutations.
AB  - BACKGROUND: Prostate cancer is one of the most common cancers which develops by
      mutations and/or other genetic alterations in specific genes. Regarding the
      previous studies in literature predominant mutations take place in KRAS, BRAF,
      and EGFR genes in special types of cancers. In this research, we attempt to
      identify the prevalence and significant role of the possible mutations in EGFR
      exons 18-21, KRAS codon 12, 13, and 61, and BRAF codon 600 mutations in tumoral
      tissue specimens from patients with prostatic adenocarcinoma. Furthermore, in
      this research, it has been attempted to investigate the molecular characteristics
      of these genes in terms of bioinformatic aspects. METHODS: A total of 35
      prostatic adenocarcinoma fresh tissue samples, enriched in neoplastic cells, were
      obtained from the Cancer Institute of Iran. The presence of mutations at codons
      12, 13 and 61 of KRAS, codon 600 of BRAF and EGFR exons 18-21 were determined by
      direct Sanger sequencing. To evaluate the molecular features, structure, and post
      translation modification of those genes, a bioinformatics survey was performed
      using the SWISS-MODEL (http://swissmodel.expasy.org) and NetPhos 2.0
      (http://www.cbs.dtu.dk/services/NetPhos/) Server. Also, using bioinformatics
      software, the phylogeny tree of the mutations was drawn. RESULTS: Mutations of
      codons 12 and 13 of KRAS were found in 2 of the 35 prostatic adenocarcinomas. Two
      cases carried homozygous mutations on exon 2 in codon 12 (G12V) and codon 13
      (G13D). Also, no mutation was detected at BRAF codon 600 and EGFR exons 18-21 in
      any of the samples. CONCLUSIONS: Based on the group of patients with prostate
      adenocarcinoma, our research shows that the mutations in codons 12 and 13 of KRAS
      are the most common in prostate carcinomas. Noting these results and the
      molecular pathway of this gene, there is a possible more perceptible role for
      this gene in the pathogenesis of prostatic carcinoma. However, according to our
      finding, as in previous studies, the role of BRAF and EGFR gene mutations in
      prostate adenocarcinoma are less than in the KRAS gene and, therefore, we assume
      that these common mutations of the KRAS gene can be used as an early determining
      marker for early diagnosis of prostate adenocarcinoma. In the future, due to the
      complexity of etiological parameters in prostate cancer development, the case
      specific tumor molecular identification and treatment for each affected subject
      are urgently needed.

PMID- 26299076
TI  - The Diagnostic Value of Oxidative/Antioxidative Balance Parameters in Venous
      Thromboembolism.
AB  - BACKGROUND: The aim of this study is to observe the association between venous
      thromboembolism (VTE) and oxidative stress and to see if there is a diagnostic
      value in the oxidative/antioxidative balance parameters like total oxidant status
      (TOS), total antioxidant status (TAS), paraoxonase-(PON1), and arylesterase (ARE)
      enzyme activities in this specific disease. METHODS: Sixty-nine patients with
      deep vein thrombosis and/or pulmonary embolism and 40 control subjects were
      included in the study. Oxidative stress index, total oxidant status, and
      antioxidant status were examined in addition to the PON1 and ARE enzyme
      activities in both groups. RESULTS: Serum PON1 and ARE activities were
      significantly lower in the VTE patients, whereas total oxidant status was higher
      in patients compared to the controls. CONCLUSIONS: This preliminary study showed
      that oxidative/antioxidative balance shifted towards the oxidative status in
      venous thromboembolism. ROC analysis results suggested that the parameters used
      in this study were not good enough to be used in the diagnosis of VTE.

PMID- 26299075
TI  - Extracellular Hydrolysis of Adenine Nucleotides and Nucleoside Adenosine is
      Higher in Patients with ST Elevation than Non-ST Elevation in Acute Myocardial
      Infarction.
AB  - BACKGROUND: The hydrolysis of adenine nucleotide linked to the membrane of the
      platelets is changed in acute myocardial infarction (AMI) probably due to a
      greater arterial blockage and cell damage in patients with ST elevation (STEMI)
      than in those without ST segment elevation (NSTEM). METHODS: This study aimed to
      compare the extracellular hydrolysis of adenine nucleotides on the platelet
      surface of STEMI and NSTEMI patients. This study was carried out with 50 patients
      with AMI (STEMI and NSTEMI). The extracellular hydrolysis of adenine nucleotides
      and nucleoside adenosine as well as the expression of NTPDase were verified in
      platelets. RESULTS: The results demonstrated that STEMI patients had
      significantly higher extracellular hydrolysis of adenine nucleotides (p < 0.001),
      ADA (adenosine deaminase) activity (p < 0.05), as well as troponin levels (p <
      0.0001) when compared to NSTEMI patients. CONCLUSIONS: Findings suggest that the
      extracellular hydrolysis of adenine nucleotides and increase in the ADA activity
      are higher in patients with STEMI than in those with NSTEMI probably because
      there was a blockage in this major arterial with a large area of damaged tissue.

PMID- 26299077
TI  - Reference Intervals for Thyroid Function and the Negative Correlation between FT4
      and HbA1c in Pregnant Women of West China.
AB  - BACKGROUND: It is necessary to establish the reference intervals of thyroid
      hormones in the three trimesters and postpartum period of healthy pregnant women
      in western China. Thyroid hormones play important roles in metabolic processes.
      METHODS: The concentrations of TPOAbs, TSH, and FT4 were measured by an ADVIA
      Centaur 2000 and HbA1c in the second trimester was measured by BIO-RAD D-10.
      RESULTS: 3435 pregnant women and 834 non-pregnant women were selected to
      establish the reference intervals. The level of TSH was the lowest (from 0.051 to
      4.489 mIU/L) in the first trimester (p < 0.001) and FT4 was lower in the second
      (from 10.97 to 15.49 pmol/L) or third trimester (from 9.49 to 16.25 pmol/L)
      compared with the other periods (p < 0.001). 20% of participants had TSH levels
      below the lower limit of the manufacturer's reference interval (0.55 mIU/L) in
      the first trimester. 6.9% in the second and 16.1% of participants in the third
      trimester had FT4 levels below the lower limit of the manufacturer's reference
      interval. In multiple regression analyses, FT4 was independently associated with
      HbA1c (OR = 0.191; 95% CI 0.052, 0.698; p = 0.012), BMI (OR = 0.697; 95% CI
      0.525, 0.927; p = 0.013), and TSH (OR = 0.647; 95% CI 0.428, 0.978; p = 0.039).
      Nonpredictive variable was age. CONCLUSIONS: The established reference intervals
      of TSH and FT4 reflected the changes of thyroid hormones veritably during
      gestation, and concentrations of FT4 in the first trimester were negatively
      correlated with HbA1c in the second trimester.

PMID- 26299078
TI  - Identification and Characterization of EDTA Test Strip Interfering Substances
      Using a Digital Color Detector.
AB  - BACKGROUND: Rapid test strips for ethylenediaminetetraacetic acid (EDTA) can be
      used to verify correct specimen types for clinical assays which require, or
      cannot be performed on, plasma collection tubes containing EDTA anticoagulant. As
      the test strip reaction chemistry is based on a color change induced by chelation
      of bismuth from a xylenol orange complex, we hypothesized that any agent capable
      of chelating bismuth might induce false positive test strip reactivity. The
      present study was therefore designed to evaluate the potential for test strip
      interference by chelating agents commonly used in the treatment of trace and
      heavy metal toxicity. METHODS: A digital color detector mounted on a 3D-printed
      test strip holder was used to quantitatively assess test strip reactivity and
      evaluate concentration-response relationships of eight commercially available
      chelating agents. RESULTS: This approach revealed the following rank-order
      potency: K2EDTA = Na2EDTA > ethylene glycol tetra-acetic acid (EGTA) >
      dimercaptosuccinic acid (DMSA) > 2,3-dimercapto-1-propanesulfonic acid (DMPS) >
      penicillamine (PEN). Both deferoxamine (DEF) and alpha lipoic acid (ALA) were non
      reactive at 10 mM concentrations. CONCLUSIONS: These experiments demonstrate that
      multiple substances can induce EDTA rapid test strip reactivity, but only at
      concentrations higher than might be expected during therapeutic chelation
      therapy. These agents are therefore unlikely to cause false positive results in
      routine clinical laboratory specimens.

PMID- 26299079
TI  - Different Expression of Erythrocyte Sedimentation Rate and C-reactive Protein in
      Papillary Thyroid Carcinoma and Nodular Goiter.
AB  - BACKGROUND: Inflammation is the seventh hallmark of cancer. Growing evidence
      indicated inflammation was linked to the progression and prognosis of many
      malignancies. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP),
      as two inflammation markers, reported frequently in the incidence and progress of
      solid cancers, but little research has concerned these markers in thyroid
      disease. In this study, the expression of ESR and CRP both in papillary thyroid
      carcinoma (PTC) and nodular goiter was investigated. METHODS: 512 patients were
      recruited to this study, including 341 PTC and 171 nodular goiters. Serum ESR and
      CRP were tested before operation. The clinical pathological factors such as
      gender, age, body mass index (BMI), tumor size, extrathyroidal extension, capsule
      invasion, lymphatic metastasis, distant metastasis, and other thyroid specific
      markers were subanalyzed in the PTC group. RESULTS: In patients with PTC, the
      mean level of ESR was 14.24 +/- 11.35 mm/h, which was lower than patients with
      nodular goiter (16.90 +/- 12.00 mm/h, p = 0.006). Meanwhile the mean level of CRP
      was 1.81 +/- 3.51 mg/L in PTC, which was lower than patients with nodular goiter
      (2.09 +/- 3.34 mg/L, p = 0.008). Subanalysis in PTC showed that the ESR/CRP level
      has no significant difference concerning the capsule invasion, extrathyroidal
      extension, T grades, lymphatic metastasis, distant metastasis, Tumor Nodulus
      Metastases (TNM) and tumor sizes (p > 0.05). Pearson's correlation analysis
      showed a positive correlation between ESR and CRP (r = 0.416, p = 0.000), ESR and
      Tg (r = 0.140, p = 0.002), CRP and Tg (r = 0.187, p = 0.000). The results of
      multivariate logistic analysis showed that gender and age were the independent
      risk factors of ESR, meanwhile age and BMI were the independent risk factors of
      CRP. CONCLUSIONS: The present study demonstrated a different expression of ESR
      and CRP between PTC and nodular goiter. Even though the difference in absolute
      figures between them was very small, it could help clinicians to distinguish the
      difference between nodular goiter and PTC to some extent. ESR/CRP may have
      potential value in distinguishing thyroid benign disease from malignant tumors.
      However, ESR and CRP had no effect on the progress of PTC. They may not have
      potential value currently in PTC staging and predicting prognosis.

PMID- 26299080
TI  - Hematocrit Level could Reflect Inflammatory Response and Disease Activity in
      Patients with Systemic Lupus Erythematosus.
AB  - BACKGROUND: The previous study has reported the association of hematocrit (HCT)
      with inflammation in several diseases. But the role of HCT in systemic lupus
      erythematosus (SLE) remained unclear. We tried to evaluate the clinical
      significance of HCT levels in patients with SLE. METHODS: A retrospective study
      including 127 adult SLE patients and 146 normal healthy controls was performed.
      HCT levels between SLE patients and normal healthy controls were compared, and
      correlations between HCT and clinical characteristics were evaluated. RESULTS:
      HCT levels in SLE patients were significantly decreased as compared with the
      normal healthy controls and negatively correlated with C-reactive protein (CRP)
      (r = -0.336, p < 0.01), erythrocyte sedimentation rate (ESR) (r = -0.332, p <
      0.01), and SLEDAI scores (r = -0.376, p < 0.01). HCT levels were also
      significantly lower in SLE patients with decreased C3 and C4 as compared with
      those in SLE patients with normal C3 and C4, indicating that HCT was positively
      correlated with C3 and C4 levels (r = 0.272, p < 0.01; r = 0.273, p < 0.01). HCT
      was decreased in SLE patients with the presence of anti-Sm and anti-RNP
      antibodies as compared with those without these auto-antibodies (p = 0.013, p <
      0.01). After adjusting RBC count and hemoglobin level, multiple linear regression
      analysis showed that HCT was independently associated with disease activity in
      SLE patients. In addition, HCT levels were elevated after treatment. CONCLUSIONS:
      HCT is correlated with CRP, ESR, and SLEDAI, suggesting that HCT could reflect
      inflammatory response and disease activity in SLE patients.

PMID- 26299081
TI  - Synovial Fluid HMGB-1 Levels are Associated with Osteoarthritis Severity.
AB  - BACKGROUND: Recent data have shown that enhanced cytokine production in knee
      osteoarthritis (OA) synovium are believed to promote pathological OA. High
      mobility group box 1 (HMGB-1) as a well-known pro-inflammatory cytokine may
      influence the development of knee OA. The purpose of this study is to analyze the
      amount of and location of HMGB-1 in OA synovium and to compare it with controls
      who are afflicted with acute meniscal or cruciate ligament tears. We also
      evaluated the relationship between the level of HMGB-1 in synovial fluid with the
      severity of synovitis, clinical symptoms (pain, stiffness, daily activity), and
      radiological changes in patients with knee OA. METHODS: Synovium and synovial
      fluid were harvested from seventy-four knee OA patients and thirty-four controls
      afflicted with acute meniscal or cruciate ligament tears. Kellgren-Lawrence (KL)
      grading system and Western Ontario McMaster University Osteoarthritis Index
      (WOMAC) assessment scale were applied to evaluate the radiological and clinic
      severity of OA patients. Additionally, for all patients, the microscopic
      synovitis was graded to evaluate the severity of synovium pathology. The location
      of HMGB-1 was determined in the synovium by immunohistochemistry. Synovium and
      synovial fluid HMGB-1 levels were measured by western blotting and enzyme-linked
      immunosorbent assay (ELISA), respectively. RESULTS: Synovium immunohistochemical
      analysis revealed that HMGB-1 displayed a strictly nuclear localization in
      controls; however, both nuclear and cytoplasmic distributions were present in OA
      patients. The percentage of HMGB-1 positive cells as well as cytoplasmic HMGB-1
      cell population in OA patients were higher than those of controls (42.5% vs.
      39.7% and 24.0% vs. 5.7%). Both synovium and synovial fluid HMGB-1 levels in OA
      patients were significantly higher than controls. In OA patients, HMGB-1 in the
      KL2/3 group was higher than in the KL4 group. Additionally, synovial fluid HMGB-1
      levels in OA patients were positively associated with the severity of synovitis,
      pain, and daily activities. CONCLUSIONS: Our results demonstrated that HMGB-1 is
      overexpressed and relocated in synovial membranes of patients with knee OA. The
      increased synovial fluid HMGB-1 levels were associated with the severity of
      synovitis, pain, and daily activities in knee OA patients. These results
      suggested that HMGB-1, as a pro-inflammatory cytokine, may play a crucial role in
      the progression of knee OA.

PMID- 26299082
TI  - Analysis of Specific IgE Level in 1,215 Patients with Allergic Diseases in
      Harbin, China.
AB  - BACKGROUND: As the incidence of allergic diseases increases, the detection of
      serum-specific immunoglobulin E (sIgE) becomes important for the diagnosis and
      management of allergic disease. This study aimed to investigate the diagnostic
      value of sIgE level in north east Chinese patients with allergic disease and
      provide more information for rational use of the sIgE results METHODS: A total of
      1,215 patients with positive allergens by an sIgE assay were enrolled from the
      Second Affiliated Hospital of Harbin Medical University, China. Serum levels of
      sIgE to fourteen allergens were detected by AllergyScreen. RESULTS: Age of the
      subjects ranged from 0 to 86 years old, and 49.1% of them (597) were less than 18
      years old. sIgE levels were grade 1 in 51.5% of them, grade 2 in 84.2%, grade 3
      in 29.5%, and grade 4 and above in 13.2%. There was a significant difference in
      the positive rank of the house dust mite mix and mixing mold between the group of
      4 to 12 year-old boys and the group of 0 to 3 year-olds and the group of over 30
      year-olds. 280 patients were positive at grade 1; if grade 2 was taken as the
      critical, 23% patients would be negative. CONCLUSIONS: The positive rank of sIgE
      was grade 1-3 in most cases and few patients were over grade 4. If grade 2 was
      taken as a positive judgment basis, 23% of patients would be mistakenly judged as
      negative. Serum sIgE levels may have value for the prevention and management for
      allergic disease.

PMID- 26299083
TI  - Troponin I can be Determined in Intraosseous Aspirates in a Porcine Shock Model.
AB  - BACKGROUND: Determination of troponin I may be important in the management of the
      critically ill patient. In medical emergencies, especially when vascular access
      is difficult to achieve, the use of intraosseous (10) needles is recommended. We
      aimed to perform a descriptive study, aiming to elucidate whether IO needles can
      be used to evaluate troponin I in a porcine model of human shock. METHODS: Eight
      pigs were anesthetized and challenged with a 6 hours continuous intravenous
      infusion of E. coli endotoxin. An IO needle (EZ-IO(r)) was inserted in the
      proximal tibia of each pig. Circulatory variables were monitored and troponin I
      was sampled from arterial and venous blood and also from bone marrow aspirates.
      RESULTS: Circulatory deterioration developed in all endotoxemic animals, which
      was reflected by a profound deterioration of left ventricular stroke work index.
      Troponin I levels were nearly identical in both arterial, venous, and IO samples
      during the first hour of endotoxemia. At 1 hour, all mean troponin I levels had
      more than doubled as compared to baseline. The troponin I levels continued to
      increase over time and were markedly elevated versus baseline levels during the
      2nd and 6th hours, regardless of sampling site. At 3 hours, IO troponin I reached
      a plateau, whereas troponin I in both arterial and venous blood continued to
      increase. CONCLUSIONS: This investigation has shown that troponin I can be
      analyzed in bone marrow aspirates in a shock model. This may be useful in medical
      emergencies, where cardiac damage is suspected to be involved. The levels of IO
      troponin I increased during the first 3 hours of shock, after which it remained
      at a high level. During this initial period there was, in parallel, a progressive
      circulatory deterioration.

PMID- 26299084
TI  - Auer Rod-Like Inclusions in Prolymphocytic Leukemia.
AB  - BACKGROUND: Prolymphocytic leukemia (PLL) is a generalized malignancy of the
      lymphoid tissue, usually of B cell type. Auer rod-like inclusions in
      prolymphocytic leukemia cells are an extremely rare event; the inclusions are
      very similar to the Auer rods morphologically. METHODS: We describe a case of B
      cell PLL presenting with Auer rod-like inclusions. The diagnosis was eventually
      proven by the morphology, cytochemical staining, immunophenotypes, and electron
      microscopy. RESULTS: Auer rod-like inclusions are pathological changes of
      mitochondria with increasing density of matrix and disappearing internal
      instructure seen through a scanning electronic microscope. CONCLUSIONS: Auer rod
      like inclusions can present in pathologically changed prolymphocytic leukemia
      cells.

PMID- 26299085
TI  - Lymphoplasmacytic Lymphoma with IgA Paraproteinemia.
AB  - BACKGROUND: Lymphoplasmacytic lymphoma is a type of B-cell Non-Hodgkin's
      lymphoma. The monoclonal immunoglobulin of IgA type is rarely seen in the
      clinical practice. METHODS: We report a patient with anemia, thrombocytopenia,
      hepatomegaly, and splenomegaly. Serum immuno-electrophoresis, bone marrow
      morphology, and flow cytometry assays were used for the diagnosis of this
      patient. RESULTS: The monoclonal gammopathy was detected in the serum protein
      electrophoresis. The serum immunoelectrophoresis was of IgA-lambda type and serum
      IgA level was high. The bone marrow aspiration exhibited a large number of
      prominent lymphoplasmacytoid lymphocytes. Immunophenotype of lymphoplasmacytoid
      lymphocytes showed: CD38+, CD138+, CD19+, CD20+. The patient was diagnosed as
      Lymphoplasmacytic Lymphoma with IgA paraproteinemia. CONCLUSIONS: For patients
      whose bone marrow aspiration reveals lymphoplasmacytoid lymphocytes while the
      monoclonal immunoglobulin is not of IgM type, further diagnosis should be
      performed to determine the characteristic of the tumor cells, in order to
      diagnose if it is a rare type of LPL.

PMID- 26299086
TI  - Alkaline Phosphatase, iPTH and Bone Turnover Markers in Chinese Advanced Chronic
      Kidney Disease Patients.
AB  - BACKGROUND: Clinicians may use several biochemical markers of bone turnover to
      assess or guide the care of patients with chronic kidney disease (CKD). The aims
      of this study are to describe changes and correlations of markers of bone
      remodeling in patients with different stages of CKD. METHODS: A total of 317
      Chinese patients with advanced CKD (stage 3-5) were enrolled. We measured serum
      levels of intact-parathyroid hormone (iPTH), N-terminal midfragment (N-MID)
      osteocalcin, procollagen type 1 amino-terminal propeptide (P1NP), beta-isomerized
      C-terminal telopeptide (beta-CTx), total alkaline phosphatase (ALP), and 25
      hydroxyvitamin D (25[OH]D). RESULTS: Levels of iPTH, N-MID osteocalcin, P1NP, and
      beta-CTx and serum phosphorus were significantly different among patients with
      different stages of CKD. Serum levels of ALP and 25(OH)D were higher in
      hemodialysis (HD) patients than in peritoneal dialysis (PD) patients. Levels of
      ALP, osteocalcin, and P1NP were significantly higher in dialysis patients than in
      non-dialysis patients. Correlations between the levels of iPTH, ALP, N-MID os-
      teocalcin, P1NP, and beta-CTx were statistically significant but weak. There was
      no correlation between 25(OH)D and iPTH or ALP. CONCLUSIONS: Our results suggest
      that measurement of N-MID osteocalcin, P1NP, beta-CTx, and iPTH may be useful for
      assessment of CKD-mineral bone disorder (MBD) in patients with CKD.

PMID- 26299087
TI  - Hemophilus Influenzae Infections with Abscess Formation in Adults: a
      Retrospective Study Covering an Eleven-Year Period.
AB  - BACKGROUND: The aim of this study was to investigate the presence of Haemophilus
      influenzae in abscesses in adults and to determine their antibiotic resistance
      patterns. METHODS: H. influenzae strains isolated from abscesses during an eleven
      year period were determined retrospectively and the stored strains were tested
      for ampicillin, amoxicillin/calvulanic acid, cefuroxime, cefotaxime, ceftriaxone,
      ciprofloxacin, azithromycin, tetracycline, and imipenem resistance by broth
      microdilution method. The production of beta-lactamase was detected using the
      nitrocefin disc test and real-time PCR. RESULTS: A total of 26 H. influenzae
      isolated strains were found. According to ampicillin resistance and beta
      lactamase production, 2 strains were determined as BLPAR, 1 strain BLNAR, 1
      strain BLPACR, and 22 strains as BLNAS. Cefuroxime resistance was detected in 4
      strains, tetracycline resistance was detected in 4 strains, and no resistance to
      cefotaxime, ceftriaxone, imipenem, azithromycin and levofloxacin was detected.
      CONCLUSIONS: H. influenzae should be taken into account for the proper management
      of abscesses.

PMID- 26299088
TI  - Clinical Performance Evaluation of a High-Risk Human Papillomavirus Genotyping
      Test "Clinichip HPV" Using Cervical Scrape Specimens.
AB  - BACKGROUND: Persistent infection with high-risk human papillomavirus (HPV) is
      closely associated with cervical cancer development. In this study, the
      performance of the Clinichip HPV genotyping assay as a screening laboratory test
      for high-risk HPV infection was evaluated. METHODS: The genotypes of 74 cervical
      scrape specimens were tested using the Clinichip HPV assay and a conventionally
      employed HPV polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) assay. PCR sequencing was performed in cases with discrepant results
      between the Clinichip HPV test and PCR-RFLP. RESULTS: Genotyping using the
      Clinichip HPV assay and PCR-RFLP method resulted in 27% disagreement. PCR
      sequence results exhibited 79% and 21% consistency with the Clinichip HPV assay
      and PCR-RFLP method, respectively. Multiple infections were detected in 24.3% and
      12.2% of the tested cases using the Clinichip HPV assay and PCR-RFLP method,
      respectively. CONCLUSIONS: The genotyping performance of the Clinichip HPV showed
      strong concordance with PCR sequencing, although this rate was partially
      diminished in cases with multiple HPV infections. The Clinichip HPV represents a
      suitable laboratory test for the clinical screening of high-risk HPV infections.

PMID- 26299089
TI  - Setting the Gray Zone of Near-Cutoff Values in a Real-Time PCR Test for the
      Detection of Mycobacterium tuberculosis in an Intermediate Burden Country.
AB  - BACKGROUND: Recently, molecular detection of Mycobacterium tuberculosis in a
      respiratory specimens is accepted as one of the standard procedures for diagnosis
      of tuberculosis in Korea. When detecting tuberculosis using a real-time
      polymerase chain reaction (PCR), results showed the repeated near-cutoff values
      in a specimen make it difficult for the laboratory to give definitive reports as
      positive or negative. METHODS: We retrospectively evaluated clinical state of
      ninety-eight patients who were not currently taking antituberculosis medications
      and had near-cutoff values of respiratory specimens using a real-time PCR test.
      RESULTS: Sixty-eight percent of the patients had clinical tuberculosis. In
      subgroup analysis, patients less than the age of 50, 94.3% had tuberculosis while
      only 55.6% of the patients with the age of equal and over 50 had tuberculosis (p
      < 0.001). CONCLUSIONS: Setting a gray zone for real-time PCR result and give
      additional tailored information onto the interpretative report would be suggested
      for the clinical practice in an intermediate burden of tuberculosis country.

PMID- 26299090
TI  - Investigation of Concordance in Two Automated Rapid Plasma Reagin Assays and
      Conventional Manual Card Method.

PMID- 26299091
TI  - A Case of Refractory Anemia with Excess Blast-2 with Sole Trisomy 13.

PMID- 26299092
TI  - [Risk Assessment of Single-Donor (Apheresis) Platelet Concentrates and Pooled
      Whole-Blood-Derived Platelet Concentrates].
AB  - According to the risk estimates of the Robert-Koch-Institute (RKI) and the Paul
      Ehrlich-Institute (PEI) an equivalence cannot be assumed to exist between the two
      different platelet preparations. Differences between single-donor (apheresis)
      platelet concentrates (ATK) and pooled whole-blood-derived platelet concentrates
      (PTK) result from donor populations, donation intervals, and preparation
      techniques. There are no prospective randomized studies with regard to the
      clinical efficacy, which would unambiguously demonstrate equivalence of the
      therapeutic efficacy of PTK (buffy coat method) in comparison to ATK. The German
      Association of Blood Transfusion Services (StKB) points out that, due to the non
      equivalence of PTK and ATK, it is incumbent on the transfusion physician to
      select the platelet concentrate, make the appropriate disclosures, and assume
      treatment responsibility. Proper compensation for ATK and PTK must be ensured by
      the health insurance companies, whereby a special indication for the selection of
      either PTK or ATK is not given. Exceptions are patients with known HLA antibodies
      in which only selected platelet concentrates may be administered. Otherwise, no
      indication exists in the selection of the different platelet concentrates
      (Article is in German).

PMID- 26299093
TI  - Men-tor (men'tor', -ter) n. A wise and trusted counselor or teacher.

PMID- 26299095
TI  - 11th Street Family Health Services. Expanding Center in North Philadelphia a
      Model for the Future.

PMID- 26299096
TI  - 7 Cases of Proliferative Verrucous Leukoplakia: The Need for a High Clinical
      Suspicion Among Dental Practitioners. .
AB  - Proliferative verrucous leukoplakia is a distinct precancerous condition with a
      high rate of recurrence and malignant transformation over time. Proliferative
      verrucous leukoplakia has no specific histopathologic presentation; therefore,
      emphases must be on clinical presentation and history to make a diagnosis; giving
      the need for a high clinical suspicion. This condition is very important for the
      general dentist to recognize. Here we describe the clinical and microscopic
      features of seven cases of proliferative verrucous leukoplakia, with two cases
      which demonstrated malignant transformation (hybrid carcinoma and squamous cell
      carcinoma).

PMID- 26299097
TI  - Dentists must choose to opt in or out of Medicare enrollment.

PMID- 26299098
TI  - President's Message--Road Construction Ahead.

PMID- 26299099
TI  - Legislative Update--Nurses Celebrate New Workplace Safety Law.

PMID- 26299102
TI  - Agricultural Health: North Carolina and Nursing.

PMID- 26299103
TI  - Ever the Nurse--NCNA Member Reflects on Nursing Post-Retirement.

PMID- 26299104
TI  - Being an Advocate: Knowing When Hospice is Right for Your Patient.

PMID- 26299105
TI  - Making a Difference: Advocacy to Improve Pediatric Health in Eastern North
      Carolina.

PMID- 26299106
TI  - Watts School of Nursing: A Tradition of Nursing Excellence.

PMID- 26299107
TI  - Leadership Academy Update.

PMID- 26299109
TI  - North Carolina Board of Nursing Candidates.

PMID- 26299108
TI  - In Your Corner.

PMID- 26299111
TI  - Anti-Toxoplasma activities of methanolic extract of Sambucus nigra
      (Caprifoliaceae) fruits and leaves.
AB  - Toxoplasma gondii is an obligatory intracellular parasite that infects a wide
      range of warm-blooded animals and humans. Considering the severity of
      toxoplasmosis, side effects of current treatments, and the contribution of the
      ethnopharmacological knowledge for the treatment of parasitic infections, the aim
      of the present study was to investigate the efficacy of methanolic extracts from
      the fruits and leaves of Sambucus nigra against tachyzoite of T gondii. For this,
      fruits and leaves of S. nigra were collected from Mazandaran province, Iran, were
      dried under the shade, and powdered using a commercial electrical blender. For
      extractions, methanol was used as solvent. Virulent RH strain of T. gondii was
      maintained in mice and macrophages containing tachyzoites were aspirated from the
      peritoneal cavity. Four concentrations (5, 10, 25 and 50 mg/mL) of S. nigra
      extract were incubated with infected macrophages for 30, 60, 120 and 180 minutes
      and the viability of the tachyzoites were evaluated by trypan blue staining.
      Results showed that S. nigra fruit extracts at the concentrations of 5 and 10
      mg/mL killed 100% of T gondii tachyzoites after 60 and 120 minutes, respectively;
      and concentrations of 25 and 50 mg/mL killed 100% of the tachyzoites after 30
      minutes. Additionally, extract of S. nigra leaves, at the concentrations of 5, 10
      and 25 mg/mL after 180 minutes, and concentration of 50 mg/mL after 60 minutes,
      resulted with the highest efficacy. Our results showed that S. nigra has
      acceptable efficacy in vitro and the parasiticidal effect of fruit extract was
      significantly better than leaf extract. However, in vivo efficacy of this extract
      needs further investigation.

PMID- 26299112
TI  - Seasonal variations in phytoplankton diversity in the Bui dam area of the Black
      Volta in Ghana during the pre- and post-impoundment periods.
AB  - Phytoplankton constitutes the primary producers of aquatic ecosystems and
      represents the food chain base that supports the commercial fisheries of most
      water bodies. Nowadays, there is lack of information on phytoplankton assemblages
      of most reservoirs in Africa. To contribute with this knowledge, this study was
      carried out to determine the density and diversity of seasonal variations of
      phytoplankton species in the Bui dam area of the Black Volta, during the pre-
      (2011) and post-impoundment (2012) periods. For this, a three-level stratified
      random sampling approach was adopted for 22 months. Phytoplankton samples were
      obtained by towing a 0.5m diameter phytoplankton net (35 microm mesh size and
      0.25m2 mouth surface area) from a non-motorized canoe through a distance of about
      100 m against the current from downstream to upstream of the river. In 2011, 35
      species of phytoplankton belonging to four classes, Bacillariophyceae (7.6%),
      Chlorophyceae (43%), Cyanophyceae (48.6%) and Euglenophyceae (0.8%) were
      identified. In the 2012 sampling, 18 species belonging to three classes,
      Bacillariophyceae (2.2%), Chlorophyceae (26.1%) and Cyanophyceae (71.7%) were
      observed. A total of 17 species of phytoplankton, including Gyrosigma sp.,
      Surirella sp., Carteria sp., Chlosterium sp., Chlorogonium sp., Coelastrum sp.,
      Cosmarium sp., Volvox sp., Chroococcus sp., Coelosphaerium sp., Rivularia sp. and
      Spirulina sp., were absent during the late post-impoundment period. Mean monthly
      total phytoplankton abundance decreased from June (7 384 cells/M3) to August (106
      cells/m3) in 2011. In 2012 however, mean total phytoplankton decreased from
      February (1237 cels/m3) to August (4 cells/m3). The results also showed that
      variations occurred between seasons among some phytoplankton groups. The dry and
      pre-wet seasons had significantly (p<0.05) higher mean phytoplankton abundance
      than the wet season during the 22 months of sampling period. The biotic indices
      of Shannon-Wiener (HI) were homogenously distributed in the four hydrological
      seasons of the two years. The phytoplankton groups, Bacillariophyceae,
      Chlorophyceae, Euglenophyceae and total phytoplankton differed significantly
      (p<0.05) between the pre- and post-impoundment periods. The total phytoplankton
      was also significantly (p<0.05) higher in the upstream station than the
      downstream station indicating the impact of the impoundment on the downstream
      ecology. Hence, river management strategies should be implemented by hydro
      biologist to lessen the impact of the dam on the downstream ecology.

PMID- 26299113
TI  - [Diagnosis for the ecological conservation of Jatropha spp. (Euphorbiaceae) and
      their habitats in the Tehuacan-Cuicatlan Reserve, Mexico].
AB  - Jatropha spp. is an important phytogenetic resource used as food, medicine, and
      biofuel. In this study, we verified the taxonomic identity of Jatropha species
      for The Biosphere Reserve Tehuacan-Cuicatlan, and the Ecological Land Units (ELU)
      occupied by them. We assessed the conservation status of their habitats, and the
      vulnerability of Jatopha spp. populations. A total of 15 sampling sites were
      selected in the Reserve. The taxonomic work was based on specimens, original
      descriptions and type material from herbaria and those available on-line. ELUs
      were classified using biophysical variables, and gvSIG software. Ecological
      attributes were determined using a quantitative analysis by the point-centered
      quarter method; disturbance was estimated through site indicators, and the
      conservation status of the Jatropha populations was assessed using the Method for
      Evaluation of the Risk of Extinction of Plants in Mexico (MER). Jatropha
      frequently dominated the physiognomy of plant communities. The current
      distribution of Jatropha species in the Reserve was mainly determined by
      elevation, temperature, and precipitation variables. The confirmed species were
      Jatropha ciliata Sessd ex Cerv., Jatropha neopauciflora Pax, Jatropha oaxacana J.
      Jimenez Ram. & R. Torres, Jatropha rufescens Brandegee, and Jatropha rzedowskii
      J. Jimenez Ram., which are distributed in four of the six defined ELU. J.
      neopauciflora and J. rzedowskii were the most widespread species; this last
      species concur in four, J. oaxacana in two, while J. rufescens and J. ciliata in
      one ELU, being the most restricted. The richness of the genera in the associated
      communities ranged from 16 to 42. The maximum and minimum Importance Value
      Indexes were observed.in San Nicolas Tepoxtitlan for J. neopauciflora (53.75%)
      and J. rzedowskii (1.50%). The disturbance index varied from 0.22 to 0.82, with
      an average of 0.51, where the livestock variable had a high contribution.
      Considering the risk categories of MER, we concluded that J. oaxacana requires
      special protection, and J. ciliata and J. rufescens were species under extinction
      risk. The conservation status of the plant communities inhabited by populations
      of Jatropha spp. was moderate, taking into account the rate of disturbance. The
      main factors affecting the habitats of Jatropha were livestock and human
      activities; the floristic composition of the surrounding plant communities has
      low richness. These results support the urgent need of conservation strategies to
      avoid the loss of important wild growing species of Jatropha populations.

PMID- 26299114
TI  - [Pollination ecology of three sympatric species of Oenocarpus (Arecaceae) in the
      Colombian Amazon].
AB  - The understanding of pollination mechanisms is vital for developing management
      and conservation actions of economically important species. In order to
      understand the pollination mechanisms of the promising palms in the genus
      Oenocarpus (Arecaceae), we studied floral morphology and biology, of three
      sympatric species in the Colombian Amazon: O. bataua, O. balickii and O. minor.
      During the period 2010-2012 we made direct and continuous observations of
      inflorescences (visitors, pollinators, and reproductive success) of the three
      species in every development phase. We determined the association of the palms
      with their floral visitors through a complex or interaction network, whereas
      specificity or preference of the insects for each individual palm was assessed
      through paired similarity analysis, similarity analysis (ANOSIM), and ordering
      analysis based on nonmetric multidimensional scaling (NMSD). The three species
      flowered throughout the year; their inflorescences have long rachillae that hang
      close to each other from a short rachis, and they bear flowers in dyads or
      triads. Inflorescences are protandrous, thermogenic; anthesis takes place during
      daytime but pollination is nocturnal. We recorded 79 species of insects, mainly
      beetles, 33 of which visited O. balickii, 63 visited O. bataua, and 33 visited 0.
      minor. Although they shared some visitors, their abundance during the pistillate
      phase, as well as their pollen loads showed that only a few species of
      Curculionidae and Nitidulidae are the principal pollinators of the three studied
      species. Differences in network structure between staminate and pistillate
      phases, as well as difference in abundance found with the ANOSIM and NMSD
      similarity tests, suggest a high specificity of pollinators, leading to
      reproductive isolation among.the three species. Because all pollinating beetles
      were found to develop their life cycles within the inflorescences, we hypothesize
      the occurrence of a specialized system of mutual dependence between each of this
      three Oenocarpus species and their pollinators. This specialization assures a
      year-round availability of the pollinators.

PMID- 26299115
TI  - Defaunation affects Astrocaryum gratum (Arecales: Arecaceae) seed survivorship in
      a sub-montane tropical forest.
AB  - Animal-plant interactions in Neotropical forests are complex processes. Within
      these processes, mid- to large-sized mammals consume fruits and seeds from
      several species; however, because of their size these mammals are overhunted,
      resulting in defaunated forests. Our objective was to evaluate and compare seed
      removal and survivorship in a forest with no hunting, a forest with moderate or
      reduced hunting, and a forest with higher hunting pressure. We examined the
      interaction between Astrocaryum gratum and white lipped peccary (Tayassu pecari)
      to tease apart the defaunation process. To isolate and evaluate mammal seed
      removal rates and to identify the causes of mortality on Agratum, under the three
      different hunting pressures forests, we used exclosures in each one. In four
      different forest-patches for each forest, we positioned a block-treatment
      consisting of three exclosures (total exclusion, peccary exclusion, and control),
      randomly distributed 5m apart and the block-treatments spaced 50-75 m apart from
      one another. We established 15 treatments in total for each patch (5 blocks per
      patch). There were 20 blocks within each forest type. For total exclusion, all
      vertebrates were excluded using galvanized wire mesh exclosures. The second, the
      peccary exclusion, was designed to stop peccaries from entering treatment units,
      providing access only to small vertebrates; larger mammals were able to access
      the treatment unit by reaching over the sides and the open top; finally, the
      Control allowed full access for all mammals. Fresh A. gratum fruits were
      collected from the forest floor under different adult trees throughout the study
      area. In each exclosure treatment, twenty Agratum seeds were placed, and their
      removal was recorded. In total, 3 600 seeds were analyzed. Seed survival was
      lower in unhunted forest compared to areas with moderate hunting and forest with
      a higher hunt pressure, supporting the hypothesis of the importance of mammals in
      seed removal. From the initial 400 seeds left for each control exclosure in each
      type of forest, there was a significant difference between the seed removal;
      1.75% seeds in the unhunted forest remained; 43.5% in the moderately hunted
      forest, and 48.5% in hunted forest. The main cause of seed mortality was white
      lipped peccaries; while in the forests without them, the main removal was caused
      by rodents and a higher insect infection was observed in the heavily hunted
      forest. Our results indicated that defaunation affects seed survivorship.

PMID- 26299116
TI  - [Contribution of tropical upland forests to carbon storage in Colombia].
AB  - The tropical montane forests in the Colombian Andean region are located above
      1500 m, and have been heavily deforested. Despite the general presumption that
      productivity and hence carbon stocks in these ecosystems are low, studies in this
      regard are scarce. This study aimed to (i) to estimate Above Ground Biomass (AGB)
      in forests located in the South of the Colombian Andean region, (ii) to identify
      the carbon storage potential of tropical montane forests dominated by the black
      oak Colombobalanus excelsa and to identify the relationship between AGB and
      altitude, and (iii) to analyze the role of tropical mountain forests in
      conservation mechanisms such as Payment for Environmental Services (PES) and
      Reducing Emissions from Deforestation and Degradation (REDD+). Twenty six 0.25 ha
      plots were randomly distributed in the forests and all trees with D > or =10 cm
      were measured. The results provided important elements for understanding the role
      of tropical montane forests as carbon sinks. The information produced can be used
      in subnational initiatives, which seek to mitigate or reduce the effects of
      deforestation through management or conservation of these ecosystems, like REDD+
      or PES. The AGB and carbon stocks results obtained were similar to those reported
      for lowland tropical forests. These could be explained by the dominance and
      abundance of C. excelsa, which accounted for over 81% of AGB/carbon. The error
      associated with the estimates of AGB/carbon was 10.58%. We found a negative and
      significant relationship between AGB and altitude, but the higher AGB values were
      in middle altitudes (approximatly = 700-1800 m), where the environmental
      conditions could be favorable to their growth. The carbon storage potential of
      these forests was higher. However, if the historical rate of the deforestation in
      the study area continues, the gross emissions of CO2e to the atmosphere could
      turn these forests in to an important emissions source. Nowadays, it is clear
      that tropical montane forests are vulnerable to deforestation, especially black
      Oak forests due to their commercial value. Given their high carbon storage
      potential, the presence of endemic species and the strategic functions of these
      ecosystems, we recommend that they should be considered relevant during REDD+,
      PES or any other conservation assessment.

PMID- 26299117
TI  - Toxicity induced by dieldrin and chlorpyrifos in the freshwater crayfish
      Cambarellus montezumae (Cambaridae).
AB  - The toxicity induced by insecticides in aquatic organisms is of utmost relevance
      because it may give a clue about the degree of health or damage of the involved
      ecosystem. In the present report, we determined the effect of dieldrin (DD) and
      chlorpyrifos (CP) on the freshwater crayfish, Cambarellus montezumae. The
      organisms (4-6 cm in diameter) were collected in the Ignacio Ramirez Reservoir,
      situated at 50 km Northeast of Mexico City, in the Rio Lerma Basin. Initially, we
      determined the LC50 value with the Probit method, then the DNA damage with single
      cell gel electrophoresis (comet assay applied at 24, 48, and 72 h of exposure) to
      the brain and hepatopancreas of animals exposed (in reconstituted water) to 0.05
      and 0.5 microg/L of each insecticide. In the hepatopancreas of the same
      organisms, we determined the lipid peroxidation by applying the TBARS test. DNA
      damage and lipid peroxidation were also evaluated with the same methods to
      organisms exposed in water from the reservoir. In regard to the LC50, at 72 h of
      exposure, we found a value of 5.1 microg/L and a value of 5.62 microg/L for DD
      and CP, respectively. The comet assay applied at different exposure times showed
      significant DNA damage to both organs, with respect to the control level. In the
      case of DD, statistical significance was observed for the two doses in the whole
      evaluated schedule. CP was genotoxic in the brain with the high dose at 72 h, and
      in the hepatopancreas with the two tested doses at all evaluated exposure times.
      Also, a significant lipid peroxidation increase was detected with the two doses
      of insecticides. In the study with water from the reservoir, a more pronounced
      DNA damage was detected. Our results showed strong DNA damage induced by both
      insecticides in the crayfish, as well as a correlation with the lipid
      peroxidation effect, suggesting that oxidative stress is involved in the
      genotoxic alteration. Our results also showed the usefulness of the studied
      organism as well as the applied tests for the evaluation of toxicological
      effects, and suggested the pertinence of applying the comet assay to other
      freshwater organisms to evaluate the bioaccumulation of insecticides.

PMID- 26299118
TI  - [Estimation of the sampling cover for dung beetles (Coleoptera: Scarabacinae) in
      Colombia].
AB  - The promotion of biodiversity conservation strategies must address the lack of
      information and the difficulty of identifying knowledge gaps that may facilitate
      our knowledge of different taxonomic groups. Dung beetles constitute one of those
      groups, despite having been proposed as an efficient bioindicator of
      environmental disturbance processes. In this work, we aimed to prepare a
      diagnosis on the state of knowledge of the subfamily Scarabaeinae, focusing on
      the cover sampling degree of this group in Colombia, with the purpose of
      identifying high-priority areas that will allow the completion of a national
      inventory. The work consisted of a bibliographical compilation using 12
      referential databases and the examination of specimens deposited in 26 national
      collections. A total of 16 940 individuals were examined, finding registers for
      232 species from 386 localities. The respective distribution cover maps were
      presented, and the cover at a national level was 10.62%. A historical analysis
      demonstrated a proliferation in the number of studies for the last three decades;
      nevertheless, a great proportion of unpublished works persists, resulting in only
      64 sampled localities with published records. The localities with the greatest
      sampling efforts were RN La Planada, Lloro, AUN Los Estoraques, PNN Tinigua and
      Mariquita. Registries for all departments were available, and the best sampled
      ones were Cundinamarca, Antioquia, Valle del Cauca and Boyaca. The ecosystems
      with the greatest number of publications are the Andean pre mountain humid
      forest, followed by the Andean mountain humid forest and the Pacific humid
      forest. Other ecosystems with few studies included mangroves, desert zones,
      natural savannahs, palm swamps, paramos, flooding forests and agroforestry
      systems. The biogeographic region with the greatest number of localities was the
      Andean region, followed by Choco-Magdalenense and Amazonia. Our results showed
      that high levels of subsampling persist and that some zones lack registries, as
      in the case of some parks of the national system of protected areas. It is
      imperative that the sampling cover is extended at a national level, focusing all
      possible efforts on collecting in those subsampled regions that have high
      conservation importance, with the main goal of completing the listing of species
      and their distribution.

PMID- 26299119
TI  - [Biomass of Cornops aquaticum (Orthoptera: Acrididae) in wetlands of Northeast
      Argentina].
AB  - The estimation of biomass in insect populations is a key factor to quantify the
      available resources and energy fluxes in ecosystems food webs. Cornops aquaticum
      is a common herbivore in Eichhornia plants in wetlands of Northeast Argentina. We
      aimed to analyse its biomass variation, related to the different grasshopper age
      categories populations in two host-plants: Eichhornia azurea and Eichhornia
      crassipes. For this, standard samplings of C. aquaticum populations were carried
      out with an entomological net of 70 cm diameter in two wetlands with E. azurea
      and E. crassipes, in Corrientes and Chaco Provinces; besides, dry weight was also
      obtained (directly and indirectly), and a regression model to indirectly estimate
      the biomass from a linear dimension measure (hind femur length) is proposed. A
      total of 2307 individuals were collected and separated in different age
      categories; their abundance and linear dimension data were obtained. The model
      proposed was InDM=lna+b*lnH (where DM=dry mass, a and b are constants and H=hind
      femur length) (R2 = 0.97). The population biomass variations of C. aquaticum were
      due to the relative abundance of each age category and the grasshopper individual
      dry weight. No significant differences were found between populations biomasses
      obtained by direct and indirect methods in E. azurea and E. crassipes floating
      meadows. This model made easier the C. aquaticum biomass calculation for both
      individuals and the population, and accelerated the processing of high number of
      samples. Finally, high biomass values of populations and individual age category
      (especially in adults) emphasize the importance of C. aquaticum as a consumer and
      a resource for predators on Eichhornia floating meadows food webs.

PMID- 26299120
TI  - Early development in the mouth-brooding cichlid fish Satanoperca pappaterra
      (Perciformes: Cichlidae).
AB  - The Neotropical region exhibits the largest diversity of fish worldwide; however,
      little is known about the early development of fish species from this region.
      Therefore, to contribute to this knowledge, this study aimed to morphologically
      describe the early stages of development (eggs, larvae and juveniles) of S.
      pappaterra using morphometric and meristic traits, and to assess changes in
      growth rates throughout larval and juvenile development by analyzing the
      relationships between various morphometric traits using analytical regression
      models. Both juvenile and adult individuals with mouth-brooded offspring were
      collected along the basins of the Cuiaba and Manso Rivers in the state of Mato
      Grosso, Brazil between March 2000 and March 2004. After the adults were
      identified, the offspring were classified according to its stage (embryonic,
      larval or juvenile period), and various morphometric and meristic variables were
      individually measured (when possible). The eggs of this species are yellow in
      color, oval shaped, show dendritic pigmentation within their yolk, have small to
      moderately sized perivitelline spaces and lack a mucous membrane and oil
      droplets. The horizontal and vertical diameters of the sample yolks ranged from
      1.43mm to 2.70mm and 1.05mm to 1.68 mm, respectively. The standard length of the
      larval period varied from 4.30mm to 7.16mm, and the standard length of the
      juvenile period varied from 10.29mm to 24.57mm. Larvae exhibit yolk sacs with
      internal dendritic pigmentation and dark punctate pigmentation in the dorsal and
      ventral body regions, whereas irregular transverse spots along the flanks are
      observed during the juvenile period. Adhesive organs are only present during the
      yolk-sac stage and at the beginning of the flexion stage. The mouth is terminal
      during all stages of development. The myomere number varied from 22 to 29 (9 to
      16 pre-anal and 10 to 16 post-anal), and the maximal numbers of fin rays and
      spines were as follows: dorsal, XVI+10; anal, IV+8; pectoral, 16; and pelvic,
      I+8. Growth analyses identified periods of important change in larval morphology
      (i.e., metamorphosis), particularly during the flexion and post-flexion stages
      and in juveniles. Therefore, the morphological development of S. pappaterra is
      consistent with the ecological requirements of this species, which primarily
      occurs in structured lentic environments with aquatic macrophytes.

PMID- 26299121
TI  - [Osteological development of the vertebral column and caudal complex of Lujanus
      guttatus (Perciformes: Lutjanidae) larvae under rearing conditions].
AB  - The spotted rose snapper (Lutjanus guttatus) is an important commercial species
      in Mexico with good culture potential. The osteological study at early stages in
      this species is an important tool to confirm normal bone structure and for the
      detection of malformations that may occur during early development. This study
      was carried out in order to evaluate and describe the normal osteological
      development of the vertebral column and caudal complex of this species grown
      under controlled conditions. For this, a total of 540 larvae of L. guttatus,
      between 2.1 and 17.5 mm of total length (TL), were cultured during 36 days;
      culture conditions were 28 degrees C, 5.74 mg/L oxygen and 32.2 ups salinity with
      standard feeding rates. To detect growth changes, a sample of 15 organisms was
      daily taken from day one until day 36 of post-hatch (DPH). Samples were processed
      following standard techniques of clearing, and cartilage (alcian blue) and bone
      staining (alizarin red). Results showed that the vertebral column is composed of
      ten vertebrae in the abdominal region, and 14 vertebrae including the urostyle in
      the caudal region. The development of the axial skeleton starts with the neural
      arches and haemal arches at 3.8 mm TL. Caudal elements such as the hypurals and
      parahypural began to develop at 4.1 mm TL. Pre-flexion and flexion of the
      notochord and the formation of all hypurals were observed between 5.3 and 5.8 mm
      TL. Ossification of the vertebrae in the abdominal region and in some neural
      arches initiated at 9.5mm TL. In the caudal region, all the neural and haemal
      arches ossified at 10.2 mm TL. All the abdominal vertebrae and their respective
      neural arches and parapophyses ossified at 11.2 mm TL, while the elements of the
      caudal complex that ossified were the hypurals, parahypurals and modified haemal
      spines. All caudal fm rays, 12 neural spines and 3 haemal arches were ossified by
      15.5 mm. The complete ossification process of this specie under laboratory
      culture conditions was observed when larvae reached 17.3 mm TL on 36 DPH.
      Detailed analysis of the osteological structures will allow a reference
      description to evaluate and detect malformations that may occur during the larval
      culture of the spotted rose snapper.

PMID- 26299122
TI  - Phenotypic differentiation of Barilius bendelisis (Cypriniformes: Cyprinidae) in
      four rivers from Central Indian Himalaya.
AB  - Barilius bendelisis, commonly known as Indian Hill Trout is an upland water fish
      of South East Asia. It belongs to the family Cyprinidae and dwells in shallow,
      clear and cold water. In this study, the intraspecific variation of Barilius
      bendelisis, on the basis of morphometric characters, was investigated.
      Altogether, 402 specimens were collected from four rivers in the Central Indian
      Himalaya. A truss network was constructed by interconnecting 12 landmarks to
      yield 30 distance variables that were extracted from digital images of specimens
      using tpsDig2 and PAST software. Allometric transformed truss measurements were
      subjected to univariate analysis of variance, factor analysis and discriminant
      analysis. All variables exhibited significant differences between the
      populations. Altogether 88% of the specimens were classified into their original
      populations (81.98% under a 'leave-one-out' procedure). With factor analysis
      measurements of the head region, the middle portion and the caudal region had
      high loadings on the first and second axis. The results indicated that B.
      bendelisis has significant phenotypic heterogeneity between the geographically
      isolated regions of Central Indian Himalaya. We hypothesize that the marked
      interspecific variation in B. bendelisis is the result of local ecological
      conditions.

PMID- 26299123
TI  - Growth stanzas in an Epinephelidae-Lutjanidae complex: considerations to length
      weight relationships.
AB  - Growth stanzas or abrupt changes in growth rates are present throughout the life
      span of fish. Identifying growth stanzas will help to adequately described growth
      taking into account that fishes are indeterminate growers. In this study, we used
      length-weight (L-W) relationships to analyze the growth stanzas in the Grouper
      Snapper complex of Southern Gulf of Mexico. For this, the type of sexuality, sex
      and different sexual maturity phase were considered in the analyses of three
      species of gonochoric Snappers (Lutjanidae) and six species of protogynous
      hermaphrodite Groupers (Epinephelidae). Welch ANOVA tests were carried out to
      deter- mine the existence of differences in length and weight between juveniles
      and adults per sex. According to the observed differences, L-W relationship
      parameters (a and b), standard error (SE b) and coefficients of determination
      (R2) were calculated for all species separately by sex and sexual maturity phase.
      Snappers' juvenile-females b-value ranged from 2.44-2.77, juvenile-males from
      2.16-2.94, adult-females from 2.63-2.80 and adult-males from 2.63-2.98. Groupers'
      b-value ranged for juvenile-females 2.66-3.20, adult-females from 2.73-3.31 and
      for adult-males 2.93-3.29. For each relationship b-value was 1-tested (-Student)
      to explore differences from the allometric coefficient (b=3), which indicated
      changes in body form. Hypothesis test, for regression slopes (b) between
      Snappers' juvenile-females vs. adult-females and juvenile-males vs. adult-males
      and Groupers' juvenile-females vs. adult-females and adult-females vs. adult
      males, indicated different growth stanzas related to gonadal development for
      Snappers, and to gonadal development and sex change in Groupers. The
      identification of growth stanzas is crucial to avoid an overestimation or
      misleading growth rate which is used in fisheries management to establish some
      target reference points, such as maximum sustainable yield or yield-per-recruit.

PMID- 26299124
TI  - [Growth and mortality parameters of Orthopristis ruber (Perciformes: Haemulidae)
      from Los Frailes Archipelaeo. Venezuela].
AB  - Orthopristis ruber is a species in high demand in Eastern Venezuela, but
      production has been decreasing in recent years. For this reason, our objective
      was to estimate the growth and mortality parameters of this resource. Monthly
      samples were collected from June 2011 to May 2012, obtaining 2980 specimens in El
      Tirano and Puerto Abajo. Data on total length (cm), total weight (g), and sex
      were recorded for each specimen. No sexual dimorphism was shown with respect to
      length (t(S)=1.113, p>0.05), so one length-weight ratio was established for both
      sexes (Wt=0.0612*Lt(2.54)); and they both exhibited minor allometric growth.
      Growth was estimated by analysis of length frequency distributions using FiSAT
      software. The estimated growth parameters (L.=39.03cm, W.=679.60g, k=0.48/year
      and t(O) = -0.32 year) showed moderately rapid growth. Length frequency data were
      adjusted to the von Bertalaniffy model, and indicated an exponential tendency of
      accelerated growth during the first years of life, followed by slow growth until
      the fish reached its maximum length. The coefficient of variation of the growth
      index (theta) demonstrated no differences in growth pattern. The natural
      mortality rate (M=0.97/year), from fishing (F=1.57/year), and total mortality
      (Z=2.54/year), were high, as well as the exploitation rate (E=0.62/year). We
      concluded that O. ruber has been fully exploited by artisanal fishers, and
      suggest a continuous study on population dynamics, to recommend optimum
      management techniques for the fishery.

PMID- 26299125
TI  - Life-stages, exploitation status and habitat use of Lutjanus goreensis
      (Perciformes: Lutjanidae) in coastal marine environments of Lagos, SW Nigeria.
AB  - The Gorean snapper, Lutanus goreensis is an important component of artisanal
      fisheries and trawl landings in the Gulf of Guinea. Despite its economic
      importance, there is a dearth of information on size structure and life history
      strategies of the species. Therefore, the objectives of this study were to
      provide baseline data on the life stages, exploitation status and habitat use for
      the species in Nigeria. Monthly samples were obtained from artisanal and trawl
      catches in Five Cowrie Creek and Lagos coastal waters between December 2008 and
      December 2010, respectively. Length-frequency distributions of the fishes caught
      were analysed to provide preliminary information on mean and modal lengths at
      capture and life-history strategies based on habitat use and estuarine-dependency
      for L. goreensis. A total of 822 specimens of L. goreensis were collected from
      Five Cowrie Creek while 377 specimens were collected from Lagos coastal waters.
      Total length varied between 7.90-34.90 cm for creek samples and from 21.90-56.10
      cm for marine samples. Length-frequency histograms showed polymodal size
      distributions in creek and marine samples. Length-frequency distributions of L.
      goreensis showed a high abundance ofjuveniles (<20 cm) and sub-adults (20-35 cm)
      which accounted for 84.1% and 68.4% of creek and marine samples examined,
      respectively. For the creek samples, fish in modal length class of 13.00-13.99 cm
      were the most exploited while in the marine samples, length classes of 29.00
      30.99 cm and 31.00-32.99cm constituted the most frequently exploited fishes.
      Increase in total lengths from the creek (mean +/- SD; 16.19 +/- 3.73 cm) to the
      marine habitat samples (32.89 +/- 6.14 cm) indicated ontogenetic shift in habitat
      use. Occurrence of a predominant juvenile population in Five Cowrie Creek by L.
      goreensis suggests estuarine-dependency and is indicative of a temporary juvenile
      habitat or a migratory corridor. In conclusion, data from the presently reported
      study and previous studies demonstrated that juvenile L. goreensis displays
      estuarine dependency and habitat flexibility. Hence, this underscores the
      importance of preserving estuarine environments as essential fish habitats to
      prevent overfishing. The study also concludes that the species is vulnerable to
      recruitment overfishing in the marine environment especially as a consequence of
      shrimping. Consequently, it advocates for ban on all fishing activities during
      peak spawning periods in breeding grounds and shrimp ground assemblage.

PMID- 26299126
TI  - Ecology and management of the invasive lionfish Pterois volitans/miles complex
      (Perciformes: Scorpaenidae) in Southern Costa Rica.
AB  - Invasive species alter ecosystem integrity and functioning and are considered one
      of the major threats to biodiversity on a global scale. The indopacific lionfish
      (Plerois volitans [Linnaeus, 1758] / miles [Bennet, 1882] complex) is the first
      non-native marine fish that has established itself in the Western Atlantic. It
      was first reported in Florida in the 1980s and then spread across the entire
      Caribbean in subsequent years. In Costa Rica, lionfish were first sighted by the
      end of 2008 and are now present in all South Caribbean reefs. Lionfish are a
      major problem for local fisherman by displacing native fish species. The aim of
      this study was to determine population density, size and diet of lionfish
      populations at four study sites along the Southern Caribbean coast of Costa Rica.
      Two of the sites were located inside the National Park Cahuita where regular
      lionfish removal occurs, whereas the other two study sides do not experiment this
      kind of management. Total length and wet weight of >450 lionfish individuals were
      determined between March and June 2011. Three relative metrics of prey quantity
      (percent number, percent frequency, and percent weight) were compared from
      approximately 300 lionfish caught with the polespear in shallow waters (<7 m
      depth). Population density was assessed weekly through visual transect surveys.
      Our results showed that lionfish preyed mostly upon teleosts and crustaceans.
      Teleosts dominated lionfish diet in percent frequency (71%) and percent weight
      (85%), whereas crustaceans had the highest percent number (58%). The top five
      teleost families of dietary importance were Pomacentridae, Acanthuridae,
      Blennidae, Labridae and Serranidae. The average total length (+/- SD) of lionfish
      was 18.7 (+/- 5.7)cm and varied significantly between sites (p<0.001). Mean
      density of lionfish was 92fish/ha with no significant differences between sites.
      Smallest fish and lowest densities were found at the two sites inside the
      National Park Cahuita. Despite management efforts on a regional scale, nationwide
      efforts are ineffective and lionfish control activities are poorly implemented.
      We conclude that there is an urgent need to develop an improved institutional
      framework for local lionfish control that promotes effective coordination among
      the relevant stakeholders in order to deal with invasive lionfish in Costa Rica.

PMID- 26299127
TI  - Acute toxicity and sublethal effects of the mixture glyphosate (Roundup Active)
      and Cosmo-Flux 411F to anuran embryos and tadpoles of four Colombian species.
AB  - Glyphosate is the most widely used herbicide in the world with application in
      agriculture, forestry, industrial weed control, garden and aquatic environments.
      However, its use is highly controversial for the possible impact on not-target
      organisms, such as amphibians, which are vanishing at an alarming and rapid rate.
      Due to the high solubility in water and ionic nature, the glyphosate requires of
      surfactants to increase activity. In addition, for the control of coca
      (Erythroxylum coca) and agricultural weeds in Colombia, formulated glyphosate is
      mixed and sprayed with the adjuvant Cosmo-Flux 411F to increase the penetration
      and activity of the herbicide. This study evaluates the acute toxic and sublethal
      effects (embryonic development, tadpole body size, tadpole swimming performance)
      of the mixture of the formulated glyphosate Roundup Active and Cosmo-Flux 411F to
      anuran embryos and tadpoles of four Colombian species under 96h laboratory
      standard tests and microcosms, which are more similar to field conditions as they
      include soil, sand and macrophytes. In the laboratory, embryos and tadpoles of
      Engystomops pustulosus were the most tolerant (LC50 = 3904 microg a.e./L; LC50=2
      799 pg a.e./L, respectively), while embryos and tadpoles of Hypsiboas crepitans
      (LC50=2 203 microg a.e./L; LC50=1424 microgg a.e./L, respectively) were the most
      sensitive. R. humboldti and R. marina presented an intermediate toxicity. Embryos
      were significantly more tolerant to the mixture than tadpoles, which could be
      likely attributed to the exclusion of chemicals by the embryonic membranes and
      the lack of organs, such as gills, which are sensitive to surfactants. Sublethal
      effects were observed for the tadpole body size, but not for the embryonic
      development and tadpole swimming performance. In microcosms, no toxicity (LC50
      could not be estimated), or sublethal responses were observed at concentrations
      up to fourfold (14.76 kg glyphosate a.e./ha) the highest field application rate
      of 3.69 kg glyphosate a.e./ha. Thus, toxicity was less in the microcosms than in
      laboratory tests, which may be attributed to the presence of sediments and
      organic matter which rapidly adsorb glyphosate and surfactants such as POEA. It
      is concluded that the mixture of glyphosate (Roundup Active) and Cosmo-Flux*411F,
      as used in the field, has a negligible toxic effect to embryos and tadpoles of
      the species tested in this study.

PMID- 26299128
TI  - [Egg size variation in egrets and herons (Aves: Ardeidae) nesting in Birama's
      swamp, Cuba].
AB  - Intraclutch egg size variation in birds depends on many ecological factors and on
      the evolutive history of each species. In wading birds, a trend to smaller eggs
      with laying order has been described, but comparative reports are scarce. In this
      study, egg size variation patterns were described for nine Egrets and Heron
      species nesting in Birama' Swamp, Cuba. The patterns were described using
      external dimensions of 3142 eggs from 1875 nests of Butorides virescens, Bubulcus
      ibis, Ardea alba, Nycticorax nycticorax, Nyctanassa violacea and four Egretta
      species, taken in the field between 1998 and 2006. Results showed that eggs were
      4.9-10% of adult weight and had volume variation coefficients between 6-9%. There
      were no general and consistent interspecies relationship between clutch size and
      egg sizes. Average volumes tend to get smaller with laying order, but it is not
      statistically detectable in Butorides and Bubulcus. Last egg was between 0.2% and
      15% smaller than the first, showing an inverse relationship with it. Intraclutch
      asymmetry is light in E. thula and fluctuating around null in Bubulcus. Size only
      predicted laying or hatching order for the last egg, in nests with more than two
      eggs, with 72.4% of confidence.

PMID- 26299129
TI  - [Seed germination of four tree species from the tropical dry forest of Valle del
      Cauca, Colombia].
AB  - The ecological restoration strategies for highly threatened ecosystems such as
      the tropical dry forest, depend on the knowledge of limiting factors of
      biological processes for the different species. Some of these include aspects
      such as germination and seed longevity of typical species present in those
      forests. In this study, we evaluated the effect of light and temperature on seed
      germination of two Fabaceae (Samanea saman and Jacaranda caucana) and two
      Bignoniaceae (Pithecellobium dulce and Tabebuia rosea) species having potential
      use in restoration, and we analyzed the seed storage behavior of these species
      for a three months period. To study the light effect, four levels of light
      quality on seeds were used (photoperiod of 12 hours of white light, darkness and
      light enriched in red and far-red, both for an hour each day), and we combined
      them with three levels of alternated temperatures (20/25, 20/30 and 25/30*C
      16/8h). For the storage behavior, two levels of seed moisture content particular
      for each species were used (low: 3.5-6.1% and high: 8.3-13.8%), with three
      storage temperatures (20, 5 and -20 degrees C) and two storage times (one and
      three months). The criterion for germination was radicle emergence which was
      measured in four replicates per treatment, and was expressed as percentage of
      germination (PG). There were significant differences in germination of Samanea
      saman and Jacaranda caucana among light and temperature treatments, with the
      lowest value in darkness treatments, whereas germination of Pithecellobium dulce
      and Tabebuia rosea did not differ between treatments (PG>90%). The most suitable
      temperature regime to promote germination in all species was 25/30 degrees C.
      These four species showed an orthodox seed storage behavior. We concluded that
      seeds of R dulce, J. caucana and T. rosea did not have an apparent influence of
      all light conditions tested in their germination response, which might confer
      advantages in colonization and establishment processes, while S. saman did not
      germinate well in darkness. We suggest the use of seeds of P dulce, J. caucana
      and T rosea in ecological restoration processes, due to their tolerance and
      germination under a wide range of temperature and light conditions. Futhermore,
      seeds of S. saman might be used in open areas such as forest gaps.

PMID- 26299130
TI  - [Aboveground biomass input of Myristicaceae tree species in the Amazonian Forest
      in Peru].
AB  - Amazonian forests are a vast storehouse of biodiversity and function as carbon
      sinks from biomass that accumulates in various tree species. In these forests,
      the taxa with the greatest contribution of biomass cannot be precisely defined,
      and the representative distribution of Myristicaceae in the Peruvian Amazon was
      the starting point for designing the present study, which aimed to quantify the
      biomass contribution of this family. For this, I analyzed the databases that
      corresponded to 38 sample units that were previously collected and that were
      provided by the TeamNetwork and RAINFOR organizations. The analysis consisted in
      the estimation of biomass using pre-established allometric equations, Kruskal
      Wallis sample comparisons, interpolation-analysis maps, and nonparametric
      multidimensional scaling (NMDS). The results showed that Myristicaceae is the
      fourth most important biomass contributor with 376.97 Mg/ha (9.92 Mg/ha in
      average), mainly due to its abundance. Additionally, the family shows a
      noticeable habitat preference for certain soil conditions in the physiographic
      units, such is the case of Virola pavonis in "varillales", within "floodplain",
      or Iryanthera tessmannii and Virola loretensis in sewage flooded areas or "igapo"
      specifically, and the preference of Virola elongata and irola surinamensis for
      white water flooded areas or "varzea" edaphic conditions of the physiographic
      units taken in the study.

PMID- 26299131
TI  - Mycorrhizal fungi isolated from native terrestrial orchids of pristine regions in
      Cordoba (Argentina).
AB  - Orchidaceae is a highly dependent group on the Rhizoctonia complex that includes
      Ceratorhiza, Moniliopsis, Epulorhiza and Rhizoctonia, for seed germination and
      the development of new orchid plants. Thus, the isolation and identification of
      orchid mycorrhizal fungi are important to understand the orchid-fungus
      relationship, which can lead to the development of efficient conservation
      strategies by in vivo germination of seeds from endangered orchid plants. The aim
      of our work was to isolate and characterize the different mycorrhizal fungi found
      in roots of terrestrial orchids from Cordoba (Argentina), and, to learn about the
      natural habit and fungal associations in the Chaco Serrano woodland pristine
      region. In this study, bloomed orchid root and rhizosphere soil samples were
      obtained in two times from Valle de Punilla during spring of 2007; samples were
      kept in plastic bags until processed within 48 hours, and mycorrhizal condition
      confirmed assessing peloton presence. A total of 23 isolates of the orchideous
      mycorrhizal Rhizoctonia complex were obtained. The isolates were studied based on
      morphological characters and ITS-rDNA sequences. Morphological characteristics as
      color of colonies, texture, growth rate, hyphal diameter and length and presence
      of sclerotia were observed on culture media. To define the number of nuclei per
      cell, the isolates were grown in Petri dishes containing water-agar (WA) for
      three days at 25 degrees C and stained with Safranine-O solution. The mycorrhizal
      fungi were grouped into binucleate (MSGib, 10 isolates) and multinucleate (MSGim,
      13 isolates) based on morphological characteristics of the colonies. We obtained
      the ITS1-5.8s-ITS4 region that was amplified using primers ITSI and ITS4. Based
      on DNA sequencing, isolates Q23 and Q29 were found to be related to species of
      Ceratobasidium. Isolates Q24 and Q4 were related to the binucleated anastomosis
      group AG-C of Rhizoctonia sp. The rest of the isolates grouped in the
      Ceratobasidium clade without grouping. From our knowledge this is the first
      report of the asso- ciation of the AG-C testers with terrestrial orchids. A high
      specificity was observed in the symbiotic relationship. As the mycorrhizal fungal
      isolates were obtained from native orchids, they could be incorporated in
      conservation programes of endangered orchids in Argentina.

PMID- 26299132
TI  - Dormancy-breaking requirements of Sophora tomentosa and Erythrina speciosa
      (Fabaceae) seeds.
AB  - The physical dormancy of seeds has been poorly studied in species from tropical
      forests, such as the Atlantic Forest. This study aimed to examine the effect of
      moderate alternating temperatures on breaking the physical dormancy of seeds, the
      morphoanatomy and histochemistry of seed coats, and to locate the
      structure/region responsible for water entrance into the seed, after breaking the
      physical dormancy of seeds of two woody Fabaceae (subfamily Faboideae) species
      that occur in the Brazilian Atlantic Forest: Sophora tomentosa and Erythrina
      speciosa. To assess temperature effect, seeds were incubated in several
      temperature values that occur in the Atlantic Forest. For morphological and
      histochemical studies, sections of fixed seeds were subjected to different
      reagents, and were observed using light or epifluorescence microscopy, to analyze
      the anatomy and histochemistry of the seed coat. Treated and nonreated seeds were
      also analyzed using a scanning electron microscope (SEM) to observe the
      morphology of the seed coat. To localize the specific site of water entrance, the
      seeds were blocked with glue in different regions and also immersed in ink. In
      the present work a maximum temperature fluctuation of 15 degrees C was applied
      during a period of 20 days and these conditions did not increase the germination
      of S. tomentosa or E. speciosa. These results may indicate that these seeds
      require larger fluctuation of temperature than the applied or/and longer period
      of exposition to the temperature fluctuation. Blocking experiments water inlet
      combined with SEM analysis of the structures of seed coat for both species showed
      that besides the lens, the hilum and micropyle are involved in water absorption
      in seeds scarified with hot water. In seeds of E. speciosa the immersion of
      scarified seeds into an aniline aqueous solution showed that the solution first
      entered the seed through the hilum. Both species showed seed morphological and
      anatomical features for seed coats of the subfamily Faboideae. Lignin and callose
      were found around all palisade layers and the water impermeability and ecological
      role of these substances are discussed in the work.

PMID- 26299133
TI  - Anaerobic degradation of anionic surfactants by indigenous microorganisms from
      sediments of a tropical polluted river in Brazil.
AB  - Linear alkylbenzene sulfonate (LAS) is widely used in the formulation of domestic
      and industrial cleaning products, the most synthetic surfactants used worldwide.
      These products can reach water bodies through the discharge of untreated sewage
      or non-effective treatments. This study evaluates the ability of the
      microorganisms found in the Tiete river sediment to degrade this synthetic
      surfactant. The experiment was conducted in a bioreactor, operated in batch
      sequences under denitrifying conditions, with cycles of 24 hours and stirring at
      150rpm, using 430 mL of sediments and 1 070mL of a synthetic substrate consisting
      of yeast extract, soluble starch, sodium bicarbonate and sucrose. LAS was added
      at different concentrations of l5mg/L and 30mg/L. The reactor operation was
      divided into the biomass adaptation to the synthetic substrate without LAS and
      three experimental conditions: a) addition of l5mg/L of LAS; b) 50% reduction the
      co-substrate concentration and 15 mg/L of LAS, and c) addition of 30mg/L of LAS
      and 100% co-substrate concentration. The results showed that the degradation
      efficiency of LAS was directly related to the addition of co-substrates and the
      population of denitrifying bacteria. The removal of LAS and nitrate can be
      achieved simultaneously in wastewater with low organic loads. The reduction in
      the co-substrates concentration was directly influenced by the number of
      denitrifying bacteria (2.2x10(13) to 1.0 x 10(8) MPN/gTVS), and consequently, LAS
      degradation (60.1 to 55.4%). The sediment microorganisms in the Tiete river can
      be used as an alternative inoculum in the treatment of wastewater with nitrate
      and LAS contamination.

PMID- 26299134
TI  - Leaf and fruit essential oil compositions of Pimenta guatemalensis (Myrtaceae)
      from Costa Rica.
AB  - Pitnenta is a genus of flowering plants in the Myrtaceae family, which has about
      15 species, mostly found in the Caribbean region of the Americas. Commonly used
      for culinary and medicinal purposes, the best known commercial species are
      allspice, P. dioica (P. officinalis) and bay rum, P. racemosa, but there is
      little information concerning P. guatemalensis. The aim of the present study was
      to identify the chemical composition of the leaf and fruit essential oils ofP.
      guatemalensis. The extraction of essential oils of P. guatemalensis growing wild
      in Costa Rica was carried out by the hydrodistillation method at atmospheric
      pressure, using a modified Clevenger type apparatus. The chemical composition of
      the oils was analyzed by capillary gas chromatographyflame ionization detector
      (GC/FID) and gas chromatography-mass spectrometry (GC/MS) using the retention
      indices on DB-5 type capillary column. A total of 103 and 63 compounds were
      identified in the leaf and fruit oils, respectively, corresponding to 96.8% and
      86.1% of the total amount of the oils. The leaf oil consisted mainly of eugenol
      (72.8%), and mono- and sesquiterpene hydrocarbons (18.2%). Among terpenes the
      major components were beta-caryophyllene (8.2%) and terpinolene (3.0%). The fruit
      oil also consisted mainly of eugenol (74.7%) and minor amounts of oxygenated mono
      and sesquiterpenes (7.3%), mainly caryophyllene oxide (3.3%). This is the first
      report of the chemical composition of the essential oils obtained from this plant
      species.

PMID- 26299136
TI  - The Star Trek tricorder.

PMID- 26299137
TI  - Next Generation 9-1-1.

PMID- 26299138
TI  - Community paramedicine.

PMID- 26299140
TI  - Clinical Decision Support.

PMID- 26299139
TI  - Golden Age of Data.

PMID- 26299141
TI  - Educated to Be Data Centric. .

PMID- 26299142
TI  - Drowning in Data, Thirsting for Knowledge.
AB  - Progressive EMS organizations need to be monitoring, capturing and measuring data
      continuously, in real-time and near-real-time to ensure quality patient care and
      optimum clinical and operational performance. Previously, this required
      exhaustive staff time and efforts, cobbling data together manually from various
      sources. We can now use EMS technologies to make useful, actionable decisions in
      near-real-time based on the data we collect--all as close to the event as
      possible. While technology is fantastic, it's still very important to keep an
      overall focus on the patient. "Treat the patient, not the monitor" is a very
      common sentiment heard in paramedic training programs around the world. The
      availability of technology doesn't preclude this statement. While crew members
      performing tasks on scene should concentrate on the job at hand, when possible,
      there should be a team leader that watches over the entire scene to help provide
      real-time direction and feedback. Crews can see what they are doing while they
      are doing it and it improves outcomes. Real-time and near-real-time information
      and feedback shows leaders where their system is headed. It gives our patients
      the best chance at the best outcomes, and gives our EMS systems the best chance
      to improve and provide measurable outcomes.

PMID- 26299143
TI  - The molecular menu: evaluating approaches to tumor profiling.

PMID- 26299144
TI  - Acute kidney injury: New biomarkers detect risk for this silent killer.

PMID- 26299145
TI  - Saliva as a diagnostic tool.

PMID- 26299146
TI  - Reviewing guidelines for primary HPV screening in women age 25 to 29.

PMID- 26299147
TI  - Liquid biopsy: its impact on cancer diagnostics.

PMID- 26299148
TI  - Better questions, better answers: reporting vs. analytics.
AB  - Tracking performance through reporting is a basic obligation for responsible lab
      management. But creative, visionary leadership requires that lab leaders ask
      better questions, reach better conclusions, and transform those conclusions into
      action to achieve better results. The clinical lab has always had the breadth of
      data to contribute to that process. With analytics, lab leaders now have the
      depth and control to effect positive change as well.

PMID- 26299149
TI  - EMR today and tomorrow. Technology, economics--and government--may drive
      adoption.

PMID- 26299150
TI  - Middleware for everywhere. Business analytics can be a GPS for the clinical
      laboratory.

PMID- 26299151
TI  - The future means flexibility: enterprise-wide EMR.

PMID- 26299153
TI  - Specimen collection automation is on the way.

PMID- 26299152
TI  - Using laboratory business intelligence to raise specimen collection quality and
      performance.

PMID- 26299154
TI  - In situ PCR: MDx meets histology.

PMID- 26299155
TI  - Group B streptococcus testing.

PMID- 26299157
TI  - Efficient nitrogen incorporation in ZnO nanowires.
AB  - One-dimensional ZnO nanowires (NWs) are a promising materials system for a
      variety of applications. Utilization of ZnO, however, requires a good
      understanding and control of material properties that are largely affected by
      intrinsic defects and contaminants. In this work we provide experimental evidence
      for unintentional incorporation of nitrogen in ZnO NWs grown by rapid thermal
      chemical vapor deposition, from electron paramagnetic resonance spectroscopy. The
      incorporated nitrogen atoms are concluded to mainly reside at oxygen sites (NO).
      The NO centers are suggested to be located in proximity to the NW surface, based
      on their reduced optical ionization energy as compared with that in bulk. This
      implies a lower defect formation energy at the NW surface as compared with its
      bulk value, consistent with theoretical predictions. The revealed facilitated
      incorporation of nitrogen in ZnO nanostructures may be advantageous for realizing
      p-type conducting ZnO via N doping. The awareness of this process can also help
      to prevent such unintentional doping in structures with desired n-type
      conductivity. 

PMID- 26299158
TI  - A controlled thiol-initiated surface polymerization strategy for the preparation
      of hydrophilic polymer stationary phases.
AB  - A controlled thiol-initiated surface polymerization strategy has been
      successfully developed and employed to prepare hydrophilic polymer stationary
      phases, which exhibited excellent chromatographic performance and protein non
      fouling properties. 

PMID- 26299159
TI  - Bound to supine sleep: Parkinson's disease and the impact of nocturnal
      immobility.
AB  - BACKGROUND: Impaired nocturnal mobility is a well-known problem in Parkinson's
      disease (PD), and clinical experience suggests a predominance of supine body
      position during sleep. However, this assumption - and potential consequences -
      still awaits objective validation by a polysomnography-based and adequately
      controlled study. METHODS: Clinical and polysomnographical analysis of 80
      consecutive PD patients and 80 control subjects carefully matched for age, sex,
      body mass index and apnea-hypopnea index. RESULTS: PD patients slept twice as
      much in supine position than control subjects (62.2 +/- 32.9% vs. 34.2 +/- 28.5%,
      p < 0.001). In PD, but not in control subjects, more supine sleep correlated with
      fewer changes in body position (rho = -0.434, p < 0.001). Longer PD disease
      duration was an independent predictor of more supine sleep in multiple linear
      regression analysis (beta = 0.389, p < 0.001); conversely, more supine sleep was
      associated with higher apnea-hypopnea index and daytime sleepiness. CONCLUSIONS:
      We confirmed that supine sleep is common in PD, and increases with longer disease
      duration. Our findings indicate that supine sleep may contribute to the overall
      disease burden by deteriorating sleep-disordered breathing and daytime vigilance.

PMID- 26299160
TI  - Imaging biomarkers in tauopathies.
AB  - Abnormally aggregated tau protein is central to the pathophysiology of
      Alzheimer's disease, frontotemporal dementia variants, progressive supranuclear
      palsy, corticobasal degeneration and chronic traumatic encephalopathy. The post
      mortem cortical density of hyperphosphorylated tau tangles correlates with pre
      morbid cognitive dysfunction and neuron loss. Selective PET ligands including
      [18F]THK5117, [18F]THK5351, [18F]AV1451 (T807) and [11C]PBB3 now provide in vivo
      imaging information about the timing and distribution of tau in the early phases
      of neurodegenerative diseases. They are potential imaging biomarkers for both
      supporting diagnosis and tracking disease progression. Here, we discuss the
      challenges posed in developing selective tau ligands as biomarkers, their state
      of development and the new clinical information that has been revealed.

PMID- 26299161
TI  - Re: Gullick J, Kwan X. Patient-directed music therapy reduces anxiety and
      sedation exposure in mechanically-ventilated patients: a research critique. Aust
      Crit Care 2015;28:103-5.

PMID- 26299162
TI  - Autocrine-paracrine regulation of the mammary gland.
AB  - The mammary gland has a remarkable capacity for regulation at a local level,
      particularly with respect to its main function: milk secretion. Regulation of
      milk synthesis has significant effects on animal and human health, at the level
      of both the mother and the neonate. Control by the mammary gland of its essential
      function, milk synthesis, is an evolutionary necessity and is therefore tightly
      regulated at a local level. For at least the last 60 yr, researchers have been
      interested in elucidating the mechanisms underpinning the mammary gland's ability
      to self-regulate, largely without the influence from systemic hormones or
      signals. By the 1960s, scientists realized the importance of milk removal in the
      capacity of the gland to produce milk and that the dynamics of this removal,
      including emptying of the alveolar spaces and frequency of milking, were
      controlled locally as opposed to traditional systemic hormonal regulation. Using
      both in vitro systems and various mammalian species, including goats, marsupials,
      humans, and dairy cows, it has been demonstrated that the mammary gland is
      largely self-regulating in its capacity to support the young, which is the
      evolutionary basis for milk production. Local control occurs at the level of the
      mammary epithelial cell through pressure and stretching negative-feedback
      mechanisms, and also in an autocrine fashion through bioactive factors within the
      milk which act as inhibitors, regulating milk secretion within the alveoli
      themselves. It is only within the last 20 to 30 yr that potential candidates for
      these bioactive factors have been examined at a molecular level. Several,
      including parathyroid hormone-related protein, growth factors (transforming
      growth factor, insulin-like growth factor, epidermal growth factor), and
      serotonin, are synthesized within and act upon the gland and possess dynamic
      receptor activity resulting in diverse effects on growth, calcium homeostasis,
      and milk composition. This review will focus on the autocrine-paracrine
      regulation of the mammary gland, with an examination of both foundational work
      and the progress made within the last 10 to 20 yr of research. 

PMID- 26299163
TI  - Effect of forage level and replacing canola meal with dry distillers grains with
      solubles in precision-fed heifer diets: Digestibility and rumen fermentation.
AB  - Objectives of this study were to determine the effects of feeding differing
      forage-to-concentrate ratios (F:C) and inclusion rates of corn dry distillers
      grain with solubles (DDGS) on digestion and rumen fermentation in precision-fed
      dairy heifer rations. A split-plot design with F:C as whole plot and DDGS
      inclusion level as sub-plot was administered in a 4-period (19 d) 4 * 4 Latin
      square. Eight rumen-cannulated Holstein heifers (12.5 +/- 0.5 mo of age and 344
      +/- 15 kg of body weight) housed in individual stalls were allocated to 2 F:C
      [50:50, low forage, or 75:25 high forage; dry matter (DM) basis] and to a
      sequence of DDGS inclusion (0, 7, 14, and 21%; DM basis). Forage was a mix of 50%
      corn silage and 50% grass hay (DM basis). Diets were fed to allow for 800 g/d of
      body weight gain and fed 1*/d. Rumen contents were sampled at -2, 0, 2, 4, 6, 8,
      10, 12, and 20 h after feeding for rumen fermentation measures. Low-forage
      rations had greater DM and organic matter apparent digestibility. We detected a
      quadratic effect for DM, organic matter, acid detergent fiber, and neutral
      detergent fiber apparent digestibility, with the 14% DDGS inclusion level having
      the highest values. Nitrogen retention decreased with increasing levels of DDGS.
      Molar proportions of acetate tended to be greater for HF and decreased as DDGS
      increased; propionate increased as DDGS increased, resulting in the opposite
      effect on acetate to propionate ratio. Rumen protozoa count decreased as DDGS
      increased. Moderate levels (14% of DM) of DDGS appear to enhance nutrient
      utilization and fermentation in precision-fed dairy heifers fed different F:C
      diets.

PMID- 26299164
TI  - Treatment of grain with organic acids at 2 different dietary phosphorus levels
      modulates ruminal microbial community structure and fermentation patterns in
      vitro.
AB  - Recent data indicate positive effects of treating grain with citric (CAc) or
      lactic acid (LAc) on the hydrolysis of phytate phosphorus (P) and fermentation
      products of the grain. This study used a semicontinuous rumen simulation
      technique to evaluate the effects of processing of barley with 50.25 g/L (wt/vol)
      CAc or 76.25 g/L LAc on microbial composition, metabolic fermentation profile,
      and nutrient degradation at low or high dietary P supply. The low P diet [3.1g of
      P per kg of dry matter (DM) of dietary P sources only] was not supplemented with
      inorganic P, whereas the high P diet was supplemented with 0.5 g of inorganic P
      per kg of DM through mineral premix and 870 mg of inorganic P/d per incubation
      fermenter via artificial saliva. Target microbes were determined using
      quantitative PCR. Data showed depression of total bacteria but not of total
      protozoa or short-chain fatty acid (SCFA) concentration with the low P diet. In
      addition, the low P diet lowered the relative abundance of Ruminococcus albus and
      decreased neutral detergent fiber (NDF) degradation and acetate proportion, but
      increased the abundance of several predominantly noncellulolytic bacterial
      species and anaerobic fungi. Treatment of grain with LAc increased the abundance
      of total bacteria in the low P diet only, and this effect was associated with a
      greater concentration of SCFA in the ruminal fluid. Interestingly, in the low P
      diet, CAc treatment of barley increased the most prevalent bacterial group, the
      genus Prevotella, in ruminal fluid and increased NDF degradation to the same
      extent as did inorganic P supplementation in the high P diet. Treatment with
      either CAc or LAc lowered the abundance of Megasphaera elsdenii but only in the
      low P diet. On the other hand, CAc treatment increased the proportion of acetate
      in the low P diet, whereas LAc treatment decreased this variable at both dietary
      P levels. The propionate proportion was significantly increased by LAc at both P
      levels, whereas butyrate increased only with the low P diet. Treatments with CAc
      or LAc reduced the degradation of CP and ammonia concentration compared with the
      control diet at both P levels. In conclusion, the beneficial effects of CAc and
      LAc treatment on specific ruminal microbes, fermentation profile, and fiber
      degradation in the low P diet suggest the potential for the treatment to
      compensate for the lack of inorganic P supplementation in vitro. Further research
      is warranted to determine the extent to which the treatment can alleviate the
      shortage of inorganic P supplementation under in vivo conditions.

PMID- 26299165
TI  - Clinical value of natriuretic peptides in chronic kidney disease.
AB  - According to several lines of evidence, natriuretic peptides (NP) are the main
      components of a cardiac-renal axis that operate in clinical conditions of
      decreased cardiac hemodynamic tolerance to regulate sodium homeostasis, blood
      pressure and vascular function. Even though it is reasonable to assume that NP
      may exert a relevant role in the adaptive response to renal mass ablation,
      evidence gathered so far suggest that this contribution is probably complex and
      dependent on the type and degree of the functional mass loss. In the last years
      NP have been increasingly used to diagnose, monitor treatment and define the
      prognosis of several cardiovascular (CV) diseases. However, in many clinical
      settings, like chronic kidney disease (CKD), the predictive value of these
      biomarkers has been questioned. In fact, it is now well established that renal
      function significantly affects the plasmatic levels of NP and that renal failure
      is the clinical condition associated with the highest plasmatic levels of these
      peptides. The complexity of the relation between NP plasmatic levels and CV and
      renal functions has obvious consequences, as it may limit the predictive value of
      NP in CV assessment of CKD patients and be a demanding exercise for clinicians
      involved in the daily management of these patients. This review describes the
      role of NP in the regulatory response to renal function loss and addresses the
      main factors involved in the clinical valorization of the peptides in the context
      of significant renal failure. 

PMID- 26299166
TI  - Cardiac complications of arteriovenous fistulas in patients with end-stage renal
      disease.
AB  - Cardiovascular disease is the leading cause of the death in dialysis patients.
      Arteriovenous fistulas (AVFs) are associated with lower mortality and are viewed
      as the desired access option in most patients with advanced kidney disease
      needing dialysis. However, AVFs have significant and potentially deleterious
      effects on cardiac functions particularly in the setting of preexisting heart
      disease. This article provides a comprehensive and contemporary review to what is
      known about the impact of AVFs on: congestive heart failure, left ventricular
      hypertrophy, pulmonary hypertension, right ventricular dysfunction, coronary
      artery disease and valvular heart disease. 

PMID- 26299167
TI  - Preemptive kidney transplantation in elderly recipients with kidneys discarded of
      very old donors: A good alternative.
AB  - BACKGROUND: The shortage of organs is a major hurdle in kidney transplantation,
      and one solution to the problem is to extend the age of the donor. However,
      organs from older donors are often discarded due to the macroscopic appearance of
      the parenchyma or major vessels. On the other hand, a large number of elderly
      patients are potential candidates for kidney transplantation, while many kidneys
      from elderly deceased donors are discarded due to a lack of age-matched
      recipients. In addition, a large number are often discarded due to the lack of
      compatible recipients among elderly patients undergoing chronic dialysis. A
      possible solution to avoid this wastage of kidneys potentially suitable for
      transplantation could be the performance of preemptive kidney transplantation
      (PKT) in carefully selected elderly patients. PKT improves graft and patient
      survival compared to other renal replacement therapy options. There is no
      information about PKT in elderly patients receiving kidneys from elderly deceased
      donors. METHODS: From 2007 to 2012, we performed a prospective observational
      study comparing 26 elderly patients receiving PKT with a control group of 26
      elderly patients receiving a first transplant after prior dialysis. RESULTS: Mean
      age of recipients was 74.3+/-2.9 years and mean age of donors was 73.8+/-4.1
      years. Induction immunosuppression was similar in both groups. Death-censored
      graft survival was 96% in the PKT group and 68% in the control group (p=0.02), at
      5 years after transplantation. Immediate and delayed graft function occurred in
      92% and 3.8%, respectively, of patients in the PKT group and 53% and 34.6% of
      patients in the control group (p=0.005). Acute rejection was significantly more
      frequent in PKT patients (23.1% vs 3.8%, p=0.043). At the end of follow-up time
      35.5+/-20.1 months, the glomerular filtration rate was similar in both groups
      (42.2+/-11.7 vs 41.7+/-11.2ml/min, p-value=0.72). Patient survival was similar in
      the two groups. CONCLUSIONS: Elderly patients with end stage of renal disease non
      dialysis may benefit from PKT elderly deceased donors whose kidneys were to be
      discarded for there are not patients in the waiting list.

PMID- 26299168
TI  - Clinical approach to kidney disease in kidney recipients in Spain.
AB  - BACKGROUND AND OBJECTIVES: In the present study, clinical criteria used by
      Spanish nephrologists when approaching chronic kidney disease (CKD) in kidney
      recipients, as well as their level of maintenance and control of renal function,
      were evaluated. METHODS: An epidemiological, observational, multicenter, nation
      wide, prospective study was carried out, with a 6-month follow-up period. Three
      hundred and sixty-eight adult patients with stage3 kidney disease after a 24
      month or longer post-transplantation follow-up period were included. Visits
      schedule included a retrospective visit, a baseline visit, an optional mid-term
      visit, and a final visit at month6. RESULTS: Mean time since kidney
      transplantation was 8.2+/-5.4years. Most common pre-transplant cardiovascular
      risk factors were high blood pressure (80.2%), followed by high cholesterol
      levels (61.7%). Serum creatinine levels showed a statistically significant
      decrease from baseline visit to 6-month visit (0.06+/-0.22; P<.0001), and
      glomerular filtration rate (GFR) reduction was -1.03+/-6.14 (P=0.0014).
      Significant independent prognostic factors for GFR worsening were: higher 24-hour
      proteinuria (OR=1.001 per mg; P=.020), longer time since transplantation
      (OR=1.009 per month; P=.017), and lower hemoglobin levels (OR=1.261 per g/dl;
      P=.038). Donor age also had some negative influence (OR=1.021 per year; P=.106).
      Biopsies were obtained in only 8% of kidney transplant recipients with stage 3
      CKD with an intervention being carried out in 25.4% of cases. CONCLUSIONS:
      Secondary markers and factors resulting in CKD progression, particularly anemia,
      are still frequently uncontrolled after kidney transplantation. Only about 2% of
      patients benefit from a therapeutic intervention based on a biopsy. Clinical
      perception differs from objective measures, which results in an obvious clinical
      inertia regarding risk factor control in such patients.

PMID- 26299169
TI  - Glucose homeostasis changes and pancreatic beta-cell proliferation after
      switching to cyclosporin in tacrolimus-induced diabetes mellitus.
AB  - BACKGROUND: Switching to cyclosporine A may result in a reversion of tacrolimus
      induced diabetes mellitus. However, mechanisms underlying such a reversion are
      still unknown. METHODS: Obese Zucker rats were used as a model for tacrolimus
      induced diabetes mellitus. A cohort of 44 obese Zucker rats received tacrolimus
      for 11 days (0.3mg/kg/day) until diabetes development; then: (a)22 rats were
      euthanized at day 12 and were used as a reference group (tacrolimus-day 12), and
      (b)22 rats on tacrolimus were shifted to cyclosporin (2.5mg/kg/day) for 5 days
      (tacrolimus-cyclosporin). An additional cohort of 22 obese Zucker rats received
      the vehicle for 17 days and were used as a control group. All animals underwent
      an intraperitoneal glucose tolerance test at the end of the study. RESULTS: beta
      cell proliferation, apoptosis and Ins2 gene expression were evaluated. Compared
      to rats in tacrolimus-day 12 group, those in tacrolimus-cyclosporin group showed
      a significant improvement in blood glucose levels in all assessment points in
      intraperitoneal glucose tolerance test. Diabetes decreased from 100% in
      tacrolimus-day 12 group to 50% in tacrolimus-cyclosporin group. Compared to
      tacrolimus-day 12 group, rats in tacrolimus-cyclosporin group showed an increased
      beta-cell proliferation, but such an increase was lower than in rats receiving
      the vehicle. Ins2 gene expressions in rats receiving tacrolimus-cyclosporin and
      rats receiving the vehicle were comparable. CONCLUSION: An early switch from
      tacrolimus to cyclosporin in tacrolimus-induced diabetes mellitus resulted in an
      increased beta-cell proliferation and reversion of diabetes in 50% of cases.

PMID- 26299170
TI  - Choosing conservative therapy in chronic kidney disease.
AB  - INTRODUCTION: Incidence of use for various renal replacement therapies is well
      known, but no data are available on conservative treatment use. OBJECTIVE: To
      assess the proportion of patients with chronic kidney failure receiving a
      conservative treatment. RESULTS: From July 1, 2013 to June 30, 2014, 232 patients
      with stage 5 CKD were seen in the Nephrology Department. After having received
      information on existing therapeutic options and having known the opinion of their
      treating physicians, 81 patients (35%) selected hemodialysis, 56 (24%) preferred
      peritoneal dialysis, 5 (2%) selected a preemptive transplant from a living donor,
      and in 90 (39%) a conservative treatment option was selected. In a univariate
      analysis using logistic regression, variables associated to a preference for
      conservative treatment were age, Charlson index excluding age, degree of walking
      difficulties, and functional dependence level, with the first three factors
      achieving statistical significance in a multivariate analysis. Presence of a
      severe disease resulting in a poor prognosis was the main reason for selecting a
      conservative treatment (49%), with the second one being patient refusal to
      receive a renal replacement therapy (26%). Mortality rate was 8.2/100 patient
      months in conservative therapy group versus 0.6/100 patient-months in patients
      receiving renal replacement therapy (P<.001). In patients receiving conservative
      therapy, baseline glomerular filtration rate at the time of study enrollment was
      the sole variable showing a significant impact on survival. CONCLUSIONS: About
      39% of patients with stage 5 CKD seen over a 1-year period in the Nephrology
      Department received conservative therapy. Age, co-morbidity, and functional
      disability were the factors associated to selecting a conservative therapy
      option.

PMID- 26299171
TI  - Assessment of dialyzer surface in online hemodiafiltration; objective choice of
      dialyzer surface area.
AB  - INTRODUCTION: Online hemodiafiltration (OL-HDF) is currently the most effective
      technique. Several randomized studies and meta-analyses have observed a reduction
      in mortality as well as a direct association with convective volume. Currently,
      it has not been well established whether a larger dialyzer surface area could
      provide better results in terms of convective and depurative effectiveness. The
      aim of this study was to assess the effect of larger dialyzer surface areas on
      convective volume and filtration capacity. MATERIAL AND METHODS: A total of 37
      patients were studied, including 31 men and 6 women, who were in the OL-HDF
      program using a 5008 Cordiax monitor with auto-substitution. Each patient was
      analyzed in 3 sessions in which only the dialyzer surface area varied (1.0, 1.4
      or 1.8 m(2)). The concentrations of urea (60 Da), creatinine (113 Da), beta2
      microglobulin (11800 Da), myoglobin (17200 Da) and alpha1-microglobulin (33000
      Da) were determined in serum at the beginning and end of each session in order to
      calculate the percent reduction of these solutes. RESULTS: The convective volume
      reached was 29.8 +/- 3.0 with 1.0 m(2), 32.7 +/- 3.1 (an increase of 6%) with 1.4
      m(2), and 34.7 +/- 3.3 L (an increase of 16%) with 1.8 m(2) (p<.001). The
      increased surface of the dialyzer showed an increase in the dialysis dose as well
      as urea and creatinine filtration. The percentage of beta2m reduction increased
      from 80.0 +/- 5.6 with 1.0 m(2) to 83.2 +/- 4.2 with 1.4 m(2) and to 84.3 +/-
      4.0% with 1.8 m(2). As for myoglobin and a1-microglobulin, significant
      differences were observed between smaller surface area (1.0 m(2)) 65.6 +/- 11 and
      20.1 +/- 9.3 and the other two surface areas, which were 70.0 +/- 8.1 and 24.1 +/
      7.1 (1.4 m(2)) and 72.3 +/- 8.7 and 28.6 +/- 12 (1.8 m(2)). CONCLUSION: The 40%
      and 80% increases in surface area led to increased convective volumes of 6 and
      16% respectively, while showing minimal differences in both the convective volume
      as well as the filtration capacity when the CUF was higher than 45 ml/h/mmHg. It
      is recommended to optimize the performance of dialyzers with the minimal surface
      area possible when adjusting the treatment prescription.

PMID- 26299172
TI  - Compliance with guidelines and predictors of mortality in hemodialysis. Learning
      from Serbia patients.
AB  - OBJECTIVES: The aims of the study were to determine the percentage of patients on
      regular hemodialysis (HD) in Serbia failing to meet KDOQI guidelines targets and
      find out factors associated with the risk of time to death and the association
      between guidelines adherence and patient outcome. METHODS: A cohort of 2153
      patients on regular HD in 24 centers (55.7% of overall HD population) in Serbia
      were followed from January 2010 to December 2012. The percentage of patients
      failing to meet KDOQI guidelines targets of dialysis dose (Kt/V>1.2), hemoglobin
      (>110g/L), serum phosphorus (1.1-1.8mmol/L), calcium (2.1-2.4mmol/L) and iPTH
      (150-300pg/mL) was determined. Cox proportional hazards analysis was used to
      select variables significantly associated with the risk of time to death.
      RESULTS: The patients were on regular HD for 5.3+/-5.3 years, dialyzed 11.8+/
      1.9h/week. Kt/V<1.2 had 42.4% of patients, hemoglobin <110g/L had 66.1%, s
      phosphorus <1.1mmol/L had 21.7% and >1.8mmol/L 28.6%, s-calcium <2.1mmol/L had
      11.7% and >2.4mmol/L 25.3%, iPTH <150pg/mL had 40% and >300pg/mL 39.7% of
      patients. Using Cox model (adjustment for patient age, gender, duration of HD
      treatment) age, duration of HD treatment, hemoglobin, iPTH and diabetic
      nephropathy were selected as significant independent predictors of time to death.
      When targets of five examined parameters were included in Cox model, target for
      KtV, hemoglobin and iPTH were found to be significant independent predictors of
      time to death. CONCLUSION: Substantial proportion of patients examined failed to
      meet KDOQI guidelines targets. The relative risk of time to death was associated
      with being outside the targets for Kt/V, hemoglobin and iPTH.

PMID- 26299173
TI  - Serum cystatin C levels in preterm newborns in our setting: Correlation with
      serum creatinine and preterm pathologies.
AB  - BACKGROUND: Cystatin C (CysC) is a renal function marker that is not as
      influenced as creatinine (Cr) by endogenous or exogenous agents, so it is
      therefore proposed as a marker in preterm infants. OBJECTIVES: To determine serum
      CysC values in preterm infants during the first week of life, compared to Cr. To
      analyze alterations caused by prematurity diseases. METHOD: The design involved a
      longitudinal, observational study of prospective cohorts. Groups were based on
      gestational age (GA): Group A (24-27 weeks), Group B (28-33 weeks), Group C (34
      36 weeks). Blood samples were collected at birth, within 48-72hours and after 7
      days of life. STATISTICS: SPSS v.20 software was used. The statistical methods
      applied included chi-squared test and ANOVA. RESULTS: A total of 109 preterm
      infants were included in the study. CysC levels were: 1.54mg/L (+/-0.28) at
      birth; 1.38mg/L (+/-0.36) within 48-72hours of life; 1.50mg/L (+/-0.31) after 7
      days (p<0.05). Cr levels were: 0.64mg/dL (+/-0.17) at birth; 0.64mg/dL (+/-0.28)
      within 48-72hours; 0.56mg/dL (+/-0.19) after 7 days (P<.05). CysC values were
      lower in hypotensive patients and those with a respiratory disease (P<.05), and
      no alterations associated with other diseases were observed. There were no
      differences in Cr levels associated with any disease. Creatinine levels were
      higher in patients <=1.500g (P<.05). CONCLUSIONS: Serum CysC decreased within 48
      72hours of life, and this decline showed significance (P<.05). The levels
      increased after 7 days in all 3 GA groups, and there was no difference in CysC
      levels among the groups. More studies in preterm infants with hypotension and
      respiratory disease are required. CysC is a better glomerular filtration (GF)
      marker in <=1.500g preterm infants.

PMID- 26299174
TI  - Hereditary apolipoprotein AI-associated renal amyloidosis: A diagnostic
      challenge.
AB  - Hereditary renal amyloidosis is an autosomal dominant condition with considerable
      overlap with other amyloidosis types. Differential diagnosis is complicated, but
      is relevant for prognosis and treatment. We describe a patient with nephrotic
      syndrome and progressive renal failure, who had a mother with renal amiloidosis.
      Renal biopsy revealed amyloid deposits in glomerular space, with absence of light
      chains and protein AA. We suspected amyloidosis with fibrinogen A alpha chain
      deposits, which is the most frequent cause of hereditary amyloidosis in Europe,
      with a glomerular preferential affectation. However, the genetic study showed a
      novel mutation in apolipoprotein AI. On reviewing the biopsy of the patient's
      mother similar glomerular deposits were found, but there were significant
      deposits in the renal medulla as well, which is typical in APO AI amyloidosis.
      The diagnosis was confirmed by immunohistochemistry. Apo AI amyloidosis is
      characterized by slowly progressive renal disease and end-stage renal disease
      occurs aproximately 3 to 15 years from initial diagnosis. Renal transplantation
      offers an acceptable graft survival and in these patients with hepatorenal
      involvement simultaneous liver and kidney transplantation could be considered. 

PMID- 26299175
TI  - Severe intradialytic hypoglycemia associated with marijuana use.

PMID- 26299176
TI  - Hypertensive crisis in a patient with a medullary lesion.

PMID- 26299177
TI  - Grover's disease in chronic kidney failure.

PMID- 26299178
TI  - Severe arrhythmia due to hypokalemia. Influence from diuretic substances.

PMID- 26299179
TI  - Subcapsular liver hematoma as a complication of an atypical hemolytic uremic
      syndrome.

PMID- 26299180
TI  - Kidney transplant recipients infected with blaKPC-2-producing Klebsiella
      pneumoniae.

PMID- 26299181
TI  - "Masked" renal disease in the elderly: Still "masked" after a 5-year follow-up?

PMID- 26299182
TI  - Systemic bioimpedance analysis in patients with implanted cardiac stimulation
      devices.

PMID- 26299183
TI  - Essential competencies for the education of nursing assistants and care helpers
      in elderly care.
AB  - BACKGROUND: The Dutch health care system faces huge challenges with regard to the
      demand on elderly care and the competencies of professionals required to meet
      this demand. However, a recent study showed that the curricula in vocational
      education for nursing assistants and care helpers remains inadequate to prepare
      them for the social and healthcare needs of the elderly. OBJECTIVE: To determine
      the essential competencies for the initial education of nursing assistants and
      care helpers in elderly care. METHODS: First, a draft version of essential
      competencies for the education of nursing assistants and care helpers in elderly
      care (N=120) was developed and approved by experts, also members of the project
      steering committee. Second, a Delphi survey was conducted to determine the
      essential competencies. The Delphi panel consisted of eleven field experts
      (teachers/educational developers) working for different vocational education
      training colleges in the Netherlands. RESULTS: Ten panel members participated in
      a two-round consensus building process via email. A definitive set of 116
      essential competencies for the initial education of nursing assistants and 42
      essential competencies for the initial education of care helpers were determined.
      CONCLUSIONS: The competencies in the definitive set are more in line with social
      and healthcare needs of the elderly like: autonomy, daily functioning prevention
      of health problems, healthy ageing and wellbeing, involvement of informal care,
      collaboration between professionals and informal care. The main challenge now is
      to translate these competencies into educational programmes for vocational
      education training colleges for care helpers and nursing assistants.
      Recommendations are made for the implementation of these competencies in the
      Dutch vocational education training colleges for care helpers and nursing
      assistants.

PMID- 26299184
TI  - Clonorchiasis.
AB  - On Aug 21, 1875, James McConnell published in The Lancet his findings from a post
      mortem examination of a 20-year-old Chinese man--undertaken at the Medical
      College Hospital in Calcutta, India--in whom he found Clonorchis sinensis in the
      bile ducts. Now, exactly 140 years later, we have a sound understanding of the
      lifecycle of this liver fluke, including key clinical, diagnostic, and
      epidemiological features. Developments in the so-called -omics sciences have not
      only advanced our knowledge of the biology and pathology of the parasite, but
      also led to the discovery of new diagnostic, drug, and vaccine targets. C
      sinensis infection is primarily related to liver and biliary disorders,
      especially cholangiocarcinoma. Clonorchiasis mainly occurs in east Asia, as a
      result of the region's social-ecological systems and deeply rooted cultural habit
      of consuming raw freshwater fish. The Kato-Katz technique, applied on fresh stool
      samples, is the most widely used diagnostic approach. Praziquantel is the
      treatment of choice and has been considered for preventive chemotherapy.
      Tribendimidine showed good safety and therapeutic profiles in phase 2 trials and
      warrants further investigation. Still today, the precise distribution, the exact
      number of infected people, subtle morbidities and pathogenesis, and the global
      burden of clonorchiasis are unknown. Integrated control strategies, consisting of
      preventive chemotherapy; information, education, and communication; environmental
      management; and capacity building through intersectoral collaboration should be
      advocated.

PMID- 26299185
TI  - Moving towards universal health coverage: lessons from 11 country studies.
AB  - In recent years, many countries have adopted universal health coverage (UHC) as a
      national aspiration. In response to increasing demand for a systematic assessment
      of global experiences with UHC, the Government of Japan and the World Bank
      collaborated on a 2-year multicountry research programme to analyse the processes
      of moving towards UHC. The programme included 11 countries (Bangladesh, Brazil,
      Ethiopia, France, Ghana, Indonesia, Japan, Peru, Thailand, Turkey, and Vietnam),
      representing diverse geographical, economic, and historical contexts. The study
      identified common challenges and opportunities and useful insights for how to
      move towards UHC. The study showed that UHC is a complex process, fraught with
      challenges, many possible pathways, and various pitfalls--but is also feasible
      and achievable. Movement towards UHC is a long-term policy engagement that needs
      both technical knowledge and political know-how. Technical solutions need to be
      accompanied by pragmatic and innovative strategies that address the national
      political economy context.

PMID- 26299187
TI  - Aphasia and the neuropsychobiology of stress.
AB  - Individuals with aphasia face significant challenges in their lives. These
      challenges stem from the difficulties caused by impaired language function.
      Impairment in the ability to successfully communicate could be a significant
      source of stress to individuals with aphasia. The purpose of the current paper is
      to present a review of the literature on the neuropsychobiology of stress and
      aphasia, give a contemporary conceptualization of stress (both neurobiological
      and psychological), offer a framework and directions for future investigations in
      stress and aphasia, and finally suggest clinical implications for this line of
      inquiry. 

PMID- 26299186
TI  - Hypoglycorrhachia in adults with community-acquired meningitis: etiologies and
      prognostic significance.
AB  - OBJECTIVES: Hypoglycorrhachia (cerebrospinal fluid (CSF) glucose <45 mg/dl) has
      been identified as a prognostic factor in patients with meningitis. The
      differential diagnosis of hypoglycorrhachia and its clinical significance was
      analyzed in the present study. METHODS: This was a retrospective study of 620
      adult patients with community-acquired meningitis (CSF white blood cell count >5
      * 10(6) cells/l and absence of a CSF shunt or recent neurosurgical procedure (<1
      month)) at eight Memorial Hermann hospitals in Houston, Texas, from January 2005
      to December 2010. An adverse clinical outcome was defined as a Glasgow outcome
      scale score of <= 4. RESULTS: Out of 620 patients with meningitis, 116 (19%) had
      hypoglycorrhachia. Etiologies of hypoglycorrhachia were idiopathic (n=40),
      bacterial (n=27), cryptococcal (n=26), viral (n=15), and tuberculous (n=4).
      Patients with hypoglycorrhachia were more likely to be immunosuppressed, have a
      history of intravenous drug use, and present with a vesicular or petechial rash,
      nausea or vomiting, nuchal rigidity, sinusitis/otitis, abnormal mental status,
      and focal neurological deficits compared to those patients without
      hypoglycorrhachia (p<0.05). Additionally, patients in the hypoglycorrhachia group
      had significantly higher rates of positive CSF and blood cultures, urgent
      treatable conditions, and abnormal cranial imaging (p<0.05). Furthermore,
      patients with hypoglycorrhachia had more adverse clinical outcomes (26/116
      (22.4%) vs. 45/504 (8.9%); p<0.001). CONCLUSION: Hypoglycorrhachia has
      significant clinical and prognostic value in the evaluation of adult patients
      with community-acquired meningitis.

PMID- 26299188
TI  - Lifespan development of phonemic and semantic fluency: Universal increase,
      differential decrease.
AB  - The aim of this study was to examine whether performance on phonemic and semantic
      fluency tasks follows similar lifespan trajectories. Data from 1212 Hebrew
      speakers aged 5-86 years were analyzed. Both linear and curvilinear quadratic
      models fit the data, reflecting a general increase in ability with age, as well
      as an increase followed by a decrease beyond this linear rise. A significant
      interaction between task type and the curvilinear effect demonstrated
      differential lifespan patterns of performance on each task. While scores improved
      similarly on the phonemic and semantic tasks during childhood, late-life decline
      was more noticeable on the semantic task, possibly due to the unique
      characteristics of aging-related word retrieval difficulties. 

PMID- 26299189
TI  - Internalizing disorders in adults with a history of childhood traumatic brain
      injury.
AB  - INTRODUCTION: While the presence of externalizing behavioral problems following
      traumatic brain injury (TBI) has been well established in the literature, less is
      known regarding internalizing disorders, and more specifically anxiety disorders,
      in such a population. This study explored the presence, rate, and incidence of
      internalizing behavior problems, including anxiety, depression, somatic
      complaints, avoidant personality symptomatology, and overall internalizing
      behavior problems in university students aged 18-25 years. METHOD: A convenience
      sample of 247 university students (197 non-TBI, 47 mild TBI, 2 moderate TBI, 1
      severe TBI) aged 18-25 years was utilized. Participants completed a self-report
      measure on behavioral functioning, the Adult Self Report (ASR), to identify
      internalizing behaviors, and a questionnaire to identify TBI history. RESULTS:
      Raw scores of behavior indicated that participants with a history of childhood
      TBI reported significantly higher levels of withdrawal, somatic complaints, and
      internalizing behavioral problems than the non-TBI participants. When analyzing
      standardized T-scores for borderline and clinically elevated ASR syndromes and
      Diagnostic and Statistical Manual of Mental Disorders (DSM)-oriented scales,
      individuals in the TBI group were significantly more likely to have higher rates
      of borderline anxiety, somatic complaints, avoidant personality problems, and
      overall internalizing disorders, and clinically elevated somatic complaints.
      Adults with a history of childhood TBI were also significantly more likely to
      report at least 1 or more DSM disorders. CONCLUSION: These results clearly
      suggest that individuals with a childhood history of TBI are at a heightened risk
      for a range of internalizing disorders in early adulthood, which is particularly
      troubling in a university sample pursuing tertiary education.

PMID- 26299191
TI  - Do immigrants improve the health of natives?
AB  - This paper studies the effects of immigration on health. Specifically, we merge
      information on individual characteristics from the German Socio-Economic Panel
      (1984-2009) with detailed local labour market characteristics, and we then
      exploit the longitudinal component of the data to determine how immigration
      affects the health of both immigrants and natives over time. We find that
      immigrants to Germany are healthier than natives upon their arrival (the healthy
      immigrant effect) but that immigrants' health deteriorates over time. We show
      that the convergence in health is heterogeneous across immigrants and occurs more
      rapidly among those working in more physically demanding jobs. Because immigrants
      are significantly more likely to work in strenuous occupations, we investigate
      whether changes in the spatial concentration of immigrants affect the health of
      the native population. Our results suggest that immigration reduces the
      likelihood that residents will report negative health outcomes. We show that
      these effects are concentrated in blue-collar occupations and are stronger among
      low-educated natives. Improvements in natives' average working conditions and
      workloads help explain the positive effects of immigration on the health of the
      native population. 

PMID- 26299190
TI  - Biocontrol of tomato plant diseases caused by Fusarium solani using a new
      isolated Aspergillus tubingensis CTM 507 glucose oxidase.
AB  - The present study focuses on the potential of glucose oxidase (GOD) as a
      promising biocontrol agent for fungal plant pathogens. In fact, a new GOD
      producing fungus was isolated and identified as an Aspergillus tubingensis. GOD
      (125 AU) has been found to inhibit Fusarium solani growth and spore production.
      Indeed, GOD caused the reduction of spores, the formation of chlamydospores, the
      induction of mycelial cords and the vacuolization of mycelium. In vivo assays,
      GOD acted as a curative treatment capable of protecting the tomato plants against
      F. solani diseases. In fact, the incidence was null in the curative treatment
      with GOD and it is around 45% for the preventive treatment. The optimization of
      media composition and culture conditions led to a 2.6-fold enhancement in enzyme
      activity, reaching 81.48U/mL. This study has demonstrated that GOD is a potent
      antifungal agent that could be used as a new biofungicide to protect plants from
      diseases. 

PMID- 26299192
TI  - Thioaptamer-conjugated CD44-targeted delivery system for the treatment of breast
      cancer in vitro and in vivo.
AB  - The high transfection efficiency and enhanced therapeutic effect of drug delivery
      systems developed in recent years imply that ligand-decorated nanocarriers are
      potentially targeted vectors for breast cancer treatment. Thioaptamer (TA)
      modified nanoparticles (NPs) designed in this study mainly consisted of ligand TA
      and dendritic polyamidoamine (PAMAM). Knowing that TA can bind to CD44-receptors
      in breast cancer, this study was intended to validate the safety and feasibility
      of systemic miRNA delivery to breast cancer cells by TA-PEG-PAMAM/miRNA
      (polyethylene glycol - PEG), testify its tumor targeting efficiency in vitro, and
      observe its biodistribution when it was administered systemically to a xenograft
      mouse model of breast cancer. The in vivo and ex vivo imaging results in human
      breast cancer tumor-bearing mice showed that TA-modification was able to enhance
      the accumulation of NPs in the breast cancer tumor. Our data showed that TA-NPs
      did not induce functional impairment to normal tissues and vital organs. TA-NPs
      may prove to be a safe and effective miRNA deliver system for breast cancer
      treatment, and could be widely used in pre-clinical and eventually clinical
      arenas of breast cancer treatment. 

PMID- 26299194
TI  - Integrated health messaging for multiple neglected zoonoses: Approaches,
      challenges and opportunities in Morocco.
AB  - Integrating the control of multiple neglected zoonoses at the community-level
      holds great potential, but critical data is missing to inform the design and
      implementation of different interventions. In this paper we present an evaluation
      of an integrated health messaging intervention, using powerpoint presentations,
      for five bacterial (brucellosis and bovine tuberculosis) and dog-associated
      (rabies, cystic echinococcosis and leishmaniasis) zoonotic diseases in Sidi Kacem
      Province, northwest Morocco. Conducted by veterinary and epidemiology students
      between 2013 and 2014, this followed a process-based approach that encouraged
      sequential adaptation of images, key messages, and delivery strategies using auto
      evaluation and end-user feedback. We describe the challenges and opportunities of
      this approach, reflecting on who was targeted, how education was conducted, and
      what tools and approaches were used. Our results showed that: (1) replacing words
      with local pictures and using "hands-on" activities improved receptivity; (2)
      information "overload" easily occurred when disease transmission pathways did not
      overlap; (3) access and receptivity at schools was greater than at the community
      level; and (4) piggy-backing on high-priority diseases like rabies offered an
      important avenue to increase knowledge of other zoonoses. We conclude by
      discussing the merits of incorporating our validated education approach into the
      school curriculum in order to influence long-term behaviour change. 

PMID- 26299193
TI  - Leisure activities and depressive symptoms in older adults with cognitive
      complaints.
AB  - BACKGROUND: Depressive symptoms are common in older adults and associated with
      increased risk of cognitive impairment. Leisure activities are often promoted for
      individuals with mood symptoms but few studies compare the effects of different
      types of leisure activities on reducing depressive symptoms. METHODS: Data were
      analyzed from participants enrolled from 2008-2009 in the Mental Activity and
      eXercise (MAX) Trial, which examined the effects of physical plus mental activity
      over 12 weeks in inactive older adults with cognitive complaints. There were no
      significant differences between intervention groups on the primary outcome of
      cognitive function or the secondary outcome of depressive symptoms; therefore,
      all participants were combined for the current analyses in which we examined
      changes in leisure activity engagement (Community Healthy Activities Model
      Program for Seniors (CHAMPS)), and changes in depressive symptoms (Geriatric
      Depression Scale (GDS)) as a function of changes in leisure activity engagement
      from baseline to post-intervention. RESULTS: Participants' mean age was 73.0
      years, 61.6% were female, and 63.6% were non-Hispanic white. There was a
      significant change in total hours per week engaged in leisure activities from
      baseline (36.7 hours, SD = 12.7) to post-intervention (40.4 hours, SD = 15.7;
      paired t-test p = 0.02), and mean change in depressive symptoms was significantly
      inversely correlated with change in leisure activity hours such that increases in
      total leisure activity were associated with decreases in depressive symptoms (r =
      -0.21, p = 0.04). CONCLUSIONS: Increasing the total amount of leisure activity
      levels may help lower depressive symptoms in inactive older adults with cognitive
      complaints.

PMID- 26299195
TI  - Further evidences for the mode of action of the larvicidal m-pentadecadienyl
      phenol isolated from Myracrodruon urundeuva seeds against Aedes aegypti.
AB  - Nowadays, dengue fever is considered the most important arbovirosis worldwide and
      its control is still based upon combating the vector Aedes aegypti. Besides
      monitoring of mosquito populations resistant to conventional insecticides, the
      search for new environmentally safe insecticides and conduction of molecular
      studies focusing on the elucidation of mode of action and possible resistance
      mechanisms are considered the key for a sustainable management of the mosquito
      vector. Thus, the present work aimed to assess changes in protein expression of
      3rd-instar larvae of Ae. aegypti after exposure to the natural insecticide m
      pentadecadienyl-phenol. Bidimensional electrophoresis followed by mass
      spectrometry resulted in identification of 12 proteins differentially expressed
      between control and treated groups. Larvae exposed to the toxic compound for 24h
      showed elevated detoxification response (glutathione-S-transferase), increased
      levels of stress-related proteins (HSP70) as well as evidence of lysosome
      stabilization to enable survival. Furthermore, expression of proteins involved in
      protection of peritrophic membrane and metabolism of lipids indicated systemic
      effect of toxic effects in treated larvae. 

PMID- 26299197
TI  - Health-related quality of life and its contributory factors in allergic rhinitis
      patients in Nigeria.
AB  - OBJECTIVES: To determine the health-related quality of life (HRQoL) in allergic
      rhinitis patients as well as identify contributory factors to patient's well
      being. METHODS: Cross-sectional study by multistage sampling. Four-month study
      duration (October 2013 to January 2014). The setting of the study was Kwara
      State, Nigeria, which has 16 local government areas with 3 senatorial districts,
      total land mass of 36,825km(2) with a population of 2,591,555. 132 consenting
      adults; 66 of them have allergic rhinitis (AR) using Score for Allergic Rhinitis
      (SFAR) instrument and 66 were age- and gender-matched controls (chi(2)=0, d.f.=1,
      P=1 and chi(2)=1.24, d.f.=2, P=0.54, respectively). Information on HRQoL was
      obtained using the 14-parameter mini-rhinoconjunctivitis quality of life
      questionnaire (mini-RQLQ). Socio-demographic variables possibly contributory to
      patient's well-being were obtained. Kruskal-Wallis and Mann-Whitney U tests were
      used to compare means. RESULTS: The overall Total Symptom Score (TSS) was 3.37+/
      0.9, while male and female allergic patients and control TSS were 3.61+/-1.0;
      3.16+/-0.8, and 0.98+/-0.2; 0.95+/-0.2, respectively. Effects of gender, marital
      status, senatorial districts, residential area and duration of symptoms had
      significant impact on the quality of life. The highest correlation with TSS and
      components of mini-RQOL questionnaire existed between nasal problems and other
      symptoms (r=0.866; 0.868). CONCLUSION: AR had appreciable impact on HRQoL of the
      participants. Gender, number of dependents, marital status, senatorial districts,
      residential area and duration of symptoms were major identifiable contributory
      factors to the patient's well-being.

PMID- 26299196
TI  - Effects of adjuvant radiotherapy on completely resected gastric cancer: A
      radiation oncologist's view of the ARTIST randomized phase III trial.
AB  - PURPOSE: We investigated which subgroups might benefit from adjuvant radiotherapy
      (RT) and suggested optimal RT targets by analyzing the results of the Adjuvant
      Chemoradiation Therapy in Stomach Cancer (ARTIST) trial. METHODS: We conducted
      randomized controlled trial in 458 gastric cancer patients. Patients were
      randomly assigned to XP (6 cycles of capecitabine and) or XPRT (2 cycles of XP+RT
      45Gy/25 fraction with capecitabine+2 cycles of XP) groups after D2 resection.
      Minimum follow-up was 5years. RESULTS: During follow-up, 77 patients (33.8%) in
      the XP arm and 60 (26.1%) in the XPRT arm experienced recurrence. Among these
      patients, locoregional recurrence (LRR) developed in 44 (9.6%; 29 in XP, 15 in
      XPRT; P=0.03). The local recurrence rate (4.8%) did not vary between arms.
      Regional recurrence was the most important difference between the two groups (23
      in the XP arm, 5 in the XPRT arm, P<0.001). LRR-free survival (LRRFS) was
      significantly different between study arms (P=0.03), especially in patients with
      LN metastasis (P=0.009). CONCLUSIONS: Adjuvant RT after D2 resection in gastric
      cancer reduced LRR, especially in group 3 LNs, and improved LRRFS. Patients with
      LN metastasis benefited more from the adjuvant RT treatment than the other
      subgroups.

PMID- 26299198
TI  - Giant fibrovascular polyp on aryepiglottic fold.
AB  - Polyps are common lesions in pharynx and larynx. A 46-year-old woman was
      transferred to our department because of the huge laryngeal mass, which was
      incidentally detected during routine health screening. On laryngoscopic exam,
      both vocal folds were not visualized due to the mass but she had no symptom such
      as hoarseness, dysphagia, and dyspnea. Awake intubation was safely performed
      using flexible bronchoscope without tracheostomy. A 4-cm sized mass on the left
      aryepiglottic fold was removed with trans-oral approach and discharged without
      complication. The pathologic diagnosis was reported as 'fibrovascular polyp'.
      Herein, we describe a unique case of giant fibrovascular polyp on aryepiglottic
      fold, which is the first report in the English literature. 

PMID- 26299199
TI  - Neodymium 1D systems: targeting new sources for field-induced slow magnetization
      relaxation.
AB  - Two non-isostructural homometallic 1D neodymium species displaying field-induced
      slow magnetization relaxations are presented together with theoretical studies.
      It is established that both systems are better described as organized 1D single
      molecule magnets (SMMs). Studies show great potential of Nd(III) ions to provide
      homometallic chains with slow magnetic relaxation. 

PMID- 26299200
TI  - Tissue- and age-dependent expression of the bovine DEFB103 gene and protein.
AB  - Beta-defensin 103 (DEFB103) shares little homology with 8 other members of the
      bovine beta-defensin family and in other species DEFB103 protein has diverse
      functions, including antimicrobial activity, a chemoattractant for dendritic
      cells, enhancing epithelial wound repair and regulating hair colour. Expression
      of the bovine DEFB103 gene was surveyed in 27 tissues and transcript was most
      abundant in tissues with stratified squamous epithelium. Oral cavity epithelial
      tissues and nictitating membrane consistently expressed high levels of DEFB103
      gene transcript. An age-dependent decrease (P < 0.05) in DEFB103 gene expression
      was only observed for buccal epithelium when comparing healthy 10- to 14-day-old
      and 10- to 12-month-old calves. A bovine herpesvirus-1 respiratory infection did,
      however, significantly (P < 0.05) up-regulate DEFB103 gene expression in the
      buccal epithelium of 6- to 8-month-old calves. Finally, DEFB103 transcript was
      low in lymph nodes draining the skin and at the limit of detection in other
      internal organs such as lung, intestine and kidney. Affinity-purified rabbit
      antisera to bovine DEFB103 was used to identify cells expressing DEFB103 protein
      within tissues with stratified squamous epitheliums. DEFB103 protein was most
      abundant in basal epithelial cells and was present in these cells prior to birth.
      Beta-defensins have been identified as regulators of dendritic cell (DC)
      chemokine responses and we observed a close association between DCs and
      epithelial cells expressing DEFB103 in both the fetus and newborn calf. In
      conclusion, bovine DEFB103 gene expression is most abundant in stratified
      squamous epithelium with DEFB103 protein localised to basal epithelial cells.
      These observations are consistent with proposed roles for DEFB103 in DC
      recruitment and repair of stratified squamous epithelium. 

PMID- 26299201
TI  - Case of mucous membrane pemphigoid with immunoglobulin G antibodies to the beta 3
      subunit of laminin-332 showing clinically Stevens-Johnson syndrome-like
      generalized blistering mucocutaneous lesions.

PMID- 26299202
TI  - Speciation and reduced hybrid female fertility in house mice.
AB  - In mammals, intrinsic postzygotic isolation has been well studied in males but
      has been less studied in females, despite the fact that female gametogenesis and
      pregnancy provide arenas for hybrid sterility or inviability that are absent in
      males. Here, we asked whether inviability or sterility is observed in female
      hybrids of Mus musculus domesticus and M. m. musculus, taxa which hybridize in
      nature and for which male sterility has been well characterized. We looked for
      parent-of-origin growth phenotypes by measuring adult body weights in F1 hybrids.
      We evaluated hybrid female fertility by crossing F1 females to a tester male and
      comparing multiple reproductive parameters between intrasubspecific controls and
      intersubspecific hybrids. Hybrid females showed no evidence of parent-of-origin
      overgrowth or undergrowth, providing no evidence for reduced viability. However,
      hybrid females had smaller litter sizes, reduced embryo survival, fewer
      ovulations, and fewer small follicles relative to controls. Significant variation
      in reproductive parameters was seen among different hybrid genotypes, suggesting
      that hybrid incompatibilities are polymorphic within subspecies. Differences in
      reproductive phenotypes in reciprocal genotypes were observed and are consistent
      with cyto-nuclear incompatibilities or incompatibilities involving genomic
      imprinting. These findings highlight the potential importance of reduced hybrid
      female fertility in the early stages of speciation. 

PMID- 26299204
TI  - Ultrafast non-radiative decay of gas-phase nucleosides.
AB  - The ultrafast photo-physical properties of DNA are crucial in providing a stable
      basis for life. Although the DNA bases efficiently absorb ultraviolet (UV)
      radiation, this energy can be dissipated to the surrounding environment by the
      rapid conversion of electronic energy to vibrational energy within about a
      picosecond. The intrinsic nature of this internal conversion process has
      previously been demonstrated through gas phase experiments on the bases,
      supported by theoretical calculations. De-excitation rates appear to be
      accelerated when individual bases are hydrogen bonded to solvent molecules or
      their complementary Watson-Crick pair. In this paper, the first gas-phase
      measurements of electronic relaxation in DNA nucleosides following UV excitation
      are reported. Using a pump-probe ionization scheme, the lifetimes for internal
      conversion to the ground state following excitation at 267 nm are found to be
      reduced by around a factor of two for adenosine, cytidine and thymidine compared
      with the isolated bases. These results are discussed in terms of a recent
      proposition that a charge transfer state provides an additional internal
      conversion pathway mediated by proton transfer through a sugar to base hydrogen
      bond. 

PMID- 26299203
TI  - Analysis of the differential expression of circulating microRNAs during the
      progression of hepatic fibrosis in patients with chronic hepatitis B virus
      infection.
AB  - Considering the limitations of liver biopsy, reliable non-invasive serum
      biomarkers of liver fibrosis are required for early diagnosis. The present study
      analyzed the expression profile of circulating micro (mi)RNAs during the
      development and progression of hepatic fibrosis in patients with chronic
      hepatitis B virus (HBV) infection, aiming to identify novel earlier diagnostic
      biomarkers. Fresh plasma samples were collected from 50 patients diagnosed with
      chronic HBV infection and hepatic fibrosis. These patients were classified into
      five groups (S0, S1, S2, S3 and S4; n=10 per group) based on Scheuer's staging
      criteria. The differential expression of the circulating miRNAs was determined by
      performing miRNA microarray hybridization. Finally, the target genes of the
      miRNAs were predicted and classified using gene ontology analysis. A total of 140
      miRNAs were detected in the S1-S4 patient groups, and their expression levels
      were >2-fold higher compared with those in the S0 group. The numbers of miRNAs
      differentially expressed in the S1-S4 patient groups were 48, 97, 84 and 56,
      respectively, with 12 miRNAs differentially expressed at all stages, 10 of which
      were upregulated and two of which were downregulated. The target genes of the
      miRNAs identified were found to be involved in 100 signal transduction pathways,
      the majority of which affected hepatic fibrosis via the TGF-/Smad, Wnt, MAPK,
      Jak/STAT and VEGF pathways. The differential expression levels of miRNAs were
      closely associated with the staging of hepatic fibrosis. The results of the
      present study provide evidence to facilitate the development and application of
      non-invasive biomarkers for earlier diagnosis of hepatic fibrosis.

PMID- 26299205
TI  - Transcriptome analysis of Bifidobacterium longum strains that show a differential
      response to hydrogen peroxide stress.
AB  - Consumer and commercial interest in foods containing probiotic bifidobacteria is
      increasing. However, because bifidobacteria are anaerobic, oxidative stress can
      diminish cell viability during production and storage of bioactive foods. We
      previously found Bifidobacterium longum strain NCC2705 had significantly greater
      intrinsic and inducible resistance to hydrogen peroxide (H2O2) than strain D2957.
      Here, we explored the basis for these differences by examining the
      transcriptional responses of both strains to sub-lethal H2O2 exposure for 5- or
      60-min. Strain NCC2705 had 288 genes that were differentially expressed after the
      5-min treatment and 114 differentially expressed genes after the 60-min
      treatment. In contrast, strain D2957 had only 21 and 90 differentially expressed
      genes after the 5- and 60-min treatments, respectively. Both strains showed up
      regulation of genes coding enzymes implicated in oxidative stress resistance,
      such as thioredoxin, thioredoxin reductase, peroxiredoxin, ferredoxin,
      glutaredoxin, and anaerobic ribonucleotide reductase, but induction levels were
      typically highest in NCC2705. Compared to D2957, NCC2705 also had more up
      regulated genes involved in transcriptional regulation and more down-regulated
      genes involved in sugar transport and metabolism. These results provide a greater
      understanding of the molecular basis for oxidative stress resistance in B. longum
      and the factors that contribute to strain-to-strain variability in survival in
      bioactive food products. 

PMID- 26299206
TI  - Complete genome sequence of Haloferax gibbonsii strain ARA6, a potential producer
      of polyhydroxyalkanoates and halocins isolated from Araruama, Rio de Janeiro,
      Brasil.
AB  - Haloferax gibbonsii strain ARA6 is a haloarchaea isolated from saline saltern
      samples from Vermelha lake, located in Araruama region, Rio de Janeiro, Brazil.
      Its genome displays 66,2% G+C content and is composed by one circular chromosome
      of 2,945,391 bp and four circular plasmids comprising 993,063 bp. This genomic
      information shows H. gibbonsii's potential for biotechnological applications and
      can also contribute to assign evolutionary traits in the genus Haloferax.

PMID- 26299208
TI  - 3-Aza pi-allyl palladium derived from imino migration in palladium-carbene: MCRs
      toward multiple substituted indole skeleton.
AB  - Palladium-catalyzed multi-component reactions (MCRs) between 2-iodoaniline, aryl
      isonitrile, N-tosylhydrazones and solvent were developed. This procedure features
      the migration of the imino group in palladium-carbene to produce a 3-aza pi-allyl
      palladium species. Then, intramolecular nucleophilic attack of the pi-allyl
      palladium species by the amino group takes place facilely, thus producing a 1,2,3
      trisubstitued indole skeleton, which has high diversity and complexity. 

PMID- 26299207
TI  - Incorporating Six Degree-of-Freedom Intervertebral Joint Stiffness in a Lumbar
      Spine Musculoskeletal Model-Method and Performance in Flexed Postures.
AB  - Intervertebral translations and rotations are likely dependent on intervertebral
      stiffness properties. The objective of this study was to incorporate realistic
      intervertebral stiffnesses in a musculoskeletal model of the lumbar spine using a
      novel force-dependent kinematics approach, and examine the effects on vertebral
      compressive loading and intervertebral motions. Predicted vertebral loading and
      intervertebral motions were compared to previously reported in vivo measurements.
      Intervertebral joint reaction forces and motions were strongly affected by
      flexion stiffness, as well as force-motion coupling of the intervertebral
      stiffness. Better understanding of intervertebral stiffness and force-motion
      coupling could improve musculoskeletal modeling, implant design, and surgical
      planning. 

PMID- 26299209
TI  - Preparation, characterisation and thermal properties of calcium alginate/n
      nonadecane microcapsules fabricated by electro-coextrusion for thermo-regulating
      textiles.
AB  - The objective of this study is to develop a new technique for producing a phase
      change material (PCM) loaded biopolymer capsule for thermo-regulating textiles.
      Electro-coextrusion process fabricated a series of microencapsulated phase change
      material (MEPCM) based on n-nonadecane core and alginate shell. The influence of
      the flow rate ratio of the shell/core on the formation, encapsulation efficiency
      and thermal behaviour of a microencapsulated PCM has been investigated. The MEPCM
      was characterised using optical microscopy and differential scanning calorimetry
      (DCS). The size and the encapsulation efficiency of a capsule decreased as the
      flow rate ratio of the shell/core increased. The PCM microcapsules contained 56
      84% n-nonadecane and the size range from 200 to 400 um, as evaluated by DSC and
      optical microscopy, respectively. The experimental results show that the electro
      coextrusion method has a potential technology for the encapsulation of PCMs for
      thermal storage.

PMID- 26299210
TI  - Analysis of lithium ion concentration and stress in the solid electrolyte
      interphase on the graphite anode.
AB  - One of the critical challenges in advancing lithium ion battery performance is
      increasing mechanical stability of the solid electrolyte interphase (SEI) layers.
      Our work aims at developing a mathematical model to study the lithium ion
      concentration and stress in the SEI on the graphite anode. The main influence
      factors on the SEI stress have been thoroughly investigated. We find that the ion
      transportation of the SEI has the underlying effects on the maximum stress in the
      graphite active layer, especially at a high charging rate. The physical
      properties of the SEI should be taken into account to obtain an accurate anode
      stress. The tensile SEI stress along the hoop direction is dominant, and should
      be regarded as the leading cause of mechanical failure for the SEI. Moreover, the
      peak stress in the SEI is independent of the charging rate, but can be
      effectively reduced by rationally designing geometric and material properties of
      anode components by: (1) decreasing modulus of the SEI itself; (2) enhancing
      tensile stiffness of the current collector; and (3) making the ratio of anode
      radius to thickness larger than ten. 

PMID- 26299212
TI  - Breast cancer and (25R)-26-hydroxycholesterol.
AB  - (25R)-26-Hydroxycholesterol (27-hydroxycholesterol) has been found to accumulate
      in breast tissue and to stimulate tumor growth via the estrogen receptor.
      Although most tissues express CYP27A1, the highest levels are in macrophages and
      most attention had been given to the production of 27-hydroxycholesterol in sub
      endothelial macrophages as part of reverse cholesterol transport. In view of the
      newly identified biologic activity, it is important to consider the determinants
      of the levels of 27-hydroxycholesterol in macrophages that infiltrate breast
      tissue. Among these determinants are the oxysterol binding proteins expressed in
      macrophages, the level of expression of CYP7B1, the oxysterol 7 alpha hydroxylase
      that generates an inactive triol, and further oxidation of 27-hydroxycholestrol
      to the C27 acid by multifunctional CYP27A1. Transport of 27-hydroxycholesterol
      from macrophages to plasma is HDL-associated. In many tissues the ratio of 27
      hydroxycholesterol to cholesterol (ng/MUg) is higher than that in plasma.
      Tamoxifen, an effective estrogen receptor antagonist that prevents breast cancer,
      also has the biologic property of blocking several steps in the lanosterol to
      cholesterol metabolic pathway. In genetically disposed women, tamoxifen may
      increase the amount of 27-hydroxycholesterol in breast tissue. 

PMID- 26299213
TI  - Primary prevention implantable cardioverter defibrillators in women: More
      questions than answers.

PMID- 26299211
TI  - Evolution of complex symbiotic relationships in a morphologically derived family
      of lichen-forming fungi.
AB  - We studied the evolutionary history of the Parmeliaceae (Lecanoromycetes,
      Ascomycota), one of the largest families of lichen-forming fungi with complex and
      variable morphologies, also including several lichenicolous fungi. We assembled a
      six-locus data set including nuclear, mitochondrial and low-copy protein-coding
      genes from 293 operational taxonomic units (OTUs). The lichenicolous lifestyle
      originated independently three times in lichenized ancestors within Parmeliaceae,
      and a new generic name is introduced for one of these fungi. In all cases, the
      independent origins occurred c. 24 million yr ago. Further, we show that the
      Paleocene, Eocene and Oligocene were key periods when diversification of major
      lineages within Parmeliaceae occurred, with subsequent radiations occurring
      primarily during the Oligocene and Miocene. Our phylogenetic hypothesis supports
      the independent origin of lichenicolous fungi associated with climatic shifts at
      the Oligocene-Miocene boundary. Moreover, diversification bursts at different
      times may be crucial factors driving the diversification of Parmeliaceae.
      Additionally, our study provides novel insight into evolutionary relationships in
      this large and diverse family of lichen-forming ascomycetes. 

PMID- 26299214
TI  - Better survival for victims of cardiac arrest occurring in sports facilities:
      From speculations to facts.

PMID- 26299215
TI  - Design and methods of the Echo WISELY (Will Inappropriate Scenarios for
      Echocardiography Lessen SignificantlY) study: An investigator-blinded randomized
      controlled trial of education and feedback intervention to reduce inappropriate
      echocardiograms.
AB  - BACKGROUND: Appropriate use criteria (AUC) for transthoracic echocardiography
      (TTE) were developed to address concerns regarding inappropriate use of TTE. A
      previous pilot study suggests that an educational and feedback intervention can
      reduce inappropriate TTEs ordered by physicians in training. It is unknown if
      this type of intervention will be effective when targeted at attending level
      physicians in a variety of clinical settings. AIMS: The aim of this
      international, multicenter study is to evaluate the hypothesis that an AUC-based
      educational and feedback intervention will reduce the proportion of inappropriate
      echocardiograms ordered by attending physicians in the ambulatory environment.
      METHODS: In an ongoing multicentered, investigator-blinded, randomized controlled
      trial across Canada and the United States, cardiologists and primary care
      physicians practicing in the ambulatory setting will be enrolled. The
      intervention arm will receive (1) a lecture outlining the AUC and most recent
      available evidence highlighting appropriate use of TTE, (2) access to the
      American Society of Echocardiography mobile phone app, and (3) individualized
      feedback reports e-mailed monthly summarizing TTE ordering behavior including
      information on inappropriate TTEs and brief explanations of the inappropriate
      designation. The control group will receive no education on TTE appropriate use
      and order TTEs as usual practice. CONCLUSIONS: The Echo WISELY (Will
      Inappropriate Scenarios for Echocardiography Lessen Significantly in an education
      RCT) study is the first multicenter randomized trial of an AUC-based educational
      intervention. The study will examine whether an education and feedback
      intervention will reduce the rate of outpatient inappropriate TTEs ordered by
      attending level cardiologists and primary care physicians (www.clinicaltrials.gov
      identifier NCT02038101).

PMID- 26299216
TI  - Randomized comparison of a sirolimus-eluting Orsiro stent with a biolimus-eluting
      Nobori stent in patients treated with percutaneous coronary intervention:
      Rationale and study design of the Scandinavian Organization for Randomized Trials
      with Clinical Outcome VII trial.
AB  - BACKGROUND: Third-generation coronary drug-eluting stents (DES) with
      biodegradable polymers have been designed to improve safety and efficacy. We
      designed a large scale registry-based randomized clinical trial to compare 2
      third-generation DES: a thin strut, cobalt-chromium DES with silicon carbide
      coating releasing sirolimus from a biodegradable polymer (O-SES, Orsiro;
      Biotronik, Bulach, Switzerland) with the stainless steel biodegradable polymer
      biolimus-eluting Nobori stents (N-BES, Nobori; Terumo, Tokyo, Japan) in an all
      comer patient population. DESIGN: The multicenter SORT OUT VII trial
      (NCT01879358) randomly assigned 2,530 patients to treatment with biodegradable
      polymer O-SES or biodegradable polymer N-BES at 3 sites in Western Denmark.
      Patients were eligible, if they were >=18 years old; had chronic stable coronary
      artery disease or acute coronary syndromes; and >=1 coronary lesion with >50%
      diameter stenosis, requiring treatment with a DES. The primary end point target
      lesion failure is a composite of cardiac death, myocardial infarction (not
      related to other than index lesion), or target lesion revascularization within 12
      months. Clinically, driven event detection based on Danish registries will be
      used. An event rate of 6.5% is assumed in each stent group. With a sample size of
      1,157 patients in each treatment arm, a 2-group large-sample normal approximation
      test of proportions with a 1-sided 5% significance level will have 90% power to
      detect noninferiority of the O-SES compared with the N-BES with a predetermined
      noninferiority margin of 3.0%. CONCLUSION: The SORT OUT VII trial will determine
      whether the biodegradable polymers O-SES is noninferior to the N-BES with respect
      to driven event.

PMID- 26299217
TI  - Community-based comprehensive lifestyle programs in patients with coronary artery
      disease: Objectives, design and expected results of Randomized Evaluation of
      Secondary Prevention by Outpatient Nurse SpEcialists 2 trial (RESPONSE 2).
AB  - Patients with coronary artery disease (CAD) are at high risk of recurrent events.
      A healthy lifestyle can significantly reduce this risk. A previous trial,
      Randomized Evaluation of Secondary Prevention by Outpatient Nurse SpEcialists
      (RESPONSE), demonstrated that nurse-coordinated outpatient clinics improve drug
      treatment of cardiovascular risk factors. However, lifestyle-related risk
      factors, including smoking, overweight, and physical inactivity, were common and
      remained largely unchanged at follow-up in most patients (66%). The aim of the
      current study is to evaluate the impact of 3 community-based lifestyle programs
      in patients after hospitalization for CAD. We are conducting a multicenter (n =
      15), randomized trial that will recruit 800 patients to test the efficacy of up
      to 3 widely available commercial lifestyle programs, aimed at patients and their
      partners, on top of usual care. These programs are aimed at smoking cessation
      (Luchtsignaal((r))), weight loss (Weight Watchers((r))), and improving physical
      activity (Philips DirectLife((r))). OUTCOMES: The primary outcome at 12months is
      the proportion of patients in whom at least 1 lifestyle risk factor is improved
      without deterioration in any of the other 2, and a relative increase of at least
      30% in this proportion is considered clinically relevant.

PMID- 26299218
TI  - Hypertrophic Cardiomyopathy Registry: The rationale and design of an
      international, observational study of hypertrophic cardiomyopathy.
AB  - Hypertrophic cardiomyopathy (HCM) is the most common monogenic heart disease with
      a frequency as high as 1 in 200. In many cases, HCM is caused by mutations in
      genes encoding the different components of the sarcomere apparatus. Hypertrophic
      cardiomyopathy is characterized by unexplained left ventricular hypertrophy,
      myofibrillar disarray, and myocardial fibrosis. The phenotypic expression is
      quite variable. Although most patients with HCM are asymptomatic, serious
      consequences are experienced in a subset of affected individuals who present
      initially with sudden cardiac death or progress to refractory heart failure. The
      Hypertrophic Cardiomyopathy Registry study is a National Heart, Lung, and Blood
      Institute-sponsored 2,750-patient, 44-site, international registry and natural
      history study designed to address limitations in extant evidence to improve
      prognostication in HCM (NCT01915615). In addition to the collection of standard
      demographic, clinical, and echocardiographic variables, patients will undergo
      state-of-the-art cardiac magnetic resonance for assessment of left ventricular
      mass and volumes as well as replacement scarring and interstitial fibrosis. In
      addition, genetic and biomarker analyses will be performed. The Hypertrophic
      Cardiomyopathy Registry has the potential to change the paradigm of risk
      stratification in HCM, using novel markers to identify those at higher risk. 

PMID- 26299220
TI  - Sex differences in health behavior change after premature acute coronary
      syndrome.
AB  - BACKGROUND: Limited information is available on the health behavior profile of
      patients with premature acute coronary syndrome (ACS). The purpose of this study
      is to desribe the health bahvior of young patients with ACS at the baseline and 1
      year post-ACS and examine sex differences. METHODS: GENESIS-PRAXY is a
      prospective cohort study of adults (18-55 years old) hospitalized with ACS from
      26 centers located in Canada, United States, and Switzerland. Data on diet,
      physical activity, smoking, alcohol consumption, and recreational drug use were
      collected through self-administered questionnaires at baseline and 1 year post
      ACS. RESULTS: Our analysis included 740 patients with complete data. At baseline,
      the health behavior profile of young patients with ACS was worse than that of the
      general population. Men had a lower fruit and vegetable intake, consumed alcohol
      more, and used recreational drugs more than women. Conversely, fewer men than
      women were smokers (34% vs 42%). At 1 year post-ACS, the proportion of those
      consuming >=5 daily servings of fruits and vegetables increased modestly (+5% vs
      +1%, for men vs women) but remained lower than the general population. Among
      women, the prevalence of smoking remained about twice as high as the general
      population. Recreational drug use also remained higher than in the general
      population. CONCLUSIONS: Despite small improvements at 1 year post-ACS, the
      health behavior profile of young patients remained worse than that of the general
      population. Greater efforts to improve health behaviors post-ACS among young
      patients are needed, and a sex-based approach may be required to ensure
      successful behavioral changes.

PMID- 26299219
TI  - Autonomic dysfunction in early breast cancer: Incidence, clinical importance, and
      underlying mechanisms.
AB  - Autonomic dysfunction represents a loss of normal autonomic control of the
      cardiovascular system associated with both sympathetic nervous system overdrive
      and reduced efficacy of the parasympathetic nervous system. Autonomic dysfunction
      is a strong predictor of future coronary heart disease, vascular disease, and
      sudden cardiac death. In the current review, we will discuss the clinical
      importance of autonomic dysfunction as a cardiovascular risk marker among breast
      cancer patients. We will review the effects of antineoplastic therapy on
      autonomic function, as well as discuss secondary exposures, such as psychological
      stress, sleep disturbances, weight gain/metabolic derangements, and loss of
      cardiorespiratory fitness, which may negatively impact autonomic function in
      breast cancer patients. Lastly, we review potential strategies to improve
      autonomic function in this population. The perspective can help guide new
      therapeutic interventions to promote longevity and cardiovascular health among
      breast cancer survivors. 

PMID- 26299221
TI  - Trends in mortality and recurrent coronary heart disease events after an acute
      myocardial infarction among Medicare beneficiaries, 2001-2009.
AB  - BACKGROUND: Few contemporary studies examine trends in recurrent coronary heart
      disease (CHD) events and mortality after acute myocardial infarction (AMI) and
      whether these trends vary by race or sex. METHODS: We used data from the national
      5% random sample of Medicare fee-for-service beneficiaries for 1999 to 2010. We
      included beneficiaries who experienced an AMI (International Classification of
      Disease [ICD] 9 410.xx, except 410.x2) between January 1, 2001, and December 31,
      2009. Each beneficiary's first AMI was included as their index event. Outcomes
      included all-cause mortality, recurrent AMI, and recurrent CHD events during the
      365days after discharge for the index AMI. To examine secular trends, we pooled
      calendar years into 3 periods (2001-2003, 2004-2006, and 2007-2009). RESULTS:
      Among 48,688 beneficiaries with index AMIs from 2001 to 2009, we observed
      decreases in the age-adjusted rates for mortality (-3.8% for each 3-year period,
      95% CI -6.1% to -1.6%, P trend = .001), recurrent AMI (-15.0%, 95% CI -18.6% to 
      11.2%, P trend < .001), and recurrent CHD events (-11.1%, 95% CI -14.0% to -8.0%,
      P trend < .001) in the 365days after the index AMI. In 2007 to 2009, blacks had
      excess risk relative to whites for mortality and recurrent AMI (black/white
      incidence rate ratio of 1.38 for mortality [95% CI 1.21-1.57] and 1.38 for
      recurrent AMI [95% CI 1.07-1.79]). CONCLUSIONS: Despite overall favorable trends
      in lower mortality and recurrent events after AMI, efforts are needed to reduce
      racial disparities.

PMID- 26299222
TI  - Incidence, diagnostic methods, and evolution of left ventricular thrombus in
      patients with anterior myocardial infarction and low left ventricular ejection
      fraction: a prospective multicenter study.
AB  - BACKGROUND AND OBJECTIVES: We aimed to assess the incidence and evolution of left
      ventricular (LV) thrombi in a high-risk population of patients with LV systolic
      dysfunction after anterior myocardial infarction (ant-MI). We also compared the
      accuracy of transthoracic echocardiography (TTE) and cardiac magnetic resonance
      imaging with contrast-delayed enhancement (CMR-DE) in detecting LV thrombi.
      METHODS: We prospectively included 100 consecutive patients with LV ejection
      fraction (LVEF) <45% at the first TTE performed <7 days after ant-MI. A second
      evaluation with TTE and CMR-DE (by blinded examiners) was performed at 30 days. A
      third TTE and assessment of clinical status were performed between 6 and 12
      months after ant-MI. RESULTS: Patients (males 71%; mean age 59.1 +/- 12.1 years;
      mean LVEF 33.5% +/- 6.0%) were included at a median of 5.5 days (interquartile
      range 25th-75th percentile 4.25-6.0 days) after ant-MI. Thrombi were detected
      among 26 (26%) patients at a median of 12.0 days after ant-MI (7 patients at 1-7
      days after MI; 15 at 8-30 days; and 4 after day 30). Sensitivity and specificity
      for LV thrombi detection were 94.7% and 98.5%, respectively, for TTE as compared
      with CMR-DE. Most thrombi (n = 24; 92.3%) disappeared after triple antithrombotic
      therapy (vitamin K antagonist in addition to dual antiplatelet therapy).
      CONCLUSION: Left ventricular thrombus is a frequent complication after ant-MI
      with systolic dysfunction. When a search for thrombus is prespecified, the
      accuracy of TTE is high as compared with CMR-DE. The best antithrombotic strategy
      is not known.

PMID- 26299223
TI  - Trends in characteristics of cardiovascular clinical trials 2001-2012.
AB  - BACKGROUND: Efficient conduct of clinical trials is essential for the timely
      generation of critical medical knowledge. METHODS: We systematically assessed
      size, duration, enrollment rates, and geographic distribution of randomized
      cardiovascular trials published between 2001 and 2012 in the 8 highest-impact
      journals in general medicine and cardiology. RESULTS: Of the 1,224 trials, 27.0%
      were conducted in North America, 36.5% in Western Europe, and 7.7% in other
      countries, and 28.8% were multiregional. Trials enrolled a median of 452 patients
      (interquartile range 167-1,530) in 20 sites (2-76). Median duration was 2.1 (1.3
      3.3) years, with an estimated enrollment rate of 1.1 (0.5-3.5) patients/site per
      month. Between 2001-2003 and 2009-2012, the proportion of North American trials
      decreased from 34.5% to 25.7% (P = .006), whereas that of multiregional trials
      (from 26.0% to 30.3%; P = .046) and trials conducted in other countries (from
      4.6% to 10.3%; P = .012) increased. Over time, trials involved more patients
      (from 400 to 500 [median]; P = .032) and sites (from 20 to 22; P = .049),
      multiregional trials involved more countries (from 12 to 18; P = .031), and
      enrollment rate declined from 1.2 to 0.9 patients/site per month (P = .017). The
      proportion of trials meeting their primary end point ("positive") decreased from
      69% to 57% (P < .001). Trials with higher enrollment rates were more likely to be
      positive (odds ratio 1.20 per doubling, 95% CI 1.12-1.29), as were industry
      sponsored compared with government-sponsored trials (odds ratio 2.62, 95% CI 1.67
      4.12). CONCLUSIONS: From 2001 to 2012, cardiovascular clinical trials have become
      larger, more global, and less likely to meet their primary end point. Enrollment
      rates have declined, requiring more sites and regions.

PMID- 26299224
TI  - The association of in-hospital guideline adherence and longitudinal postdischarge
      mortality in older patients with non-ST-segment elevation myocardial infarction.
AB  - BACKGROUND: Prior work has demonstrated that adherence to American College of
      Cardiology/American Heart Association guideline recommendations is associated
      with decreased in-hospital mortality in non-ST-segment elevation myocardial
      infarction (NSTEMI) patients; however, it is unknown whether this association
      persists after hospital discharge in older, real-world populations. METHODS: We
      evaluated 32,646 NSTEMI patients >=65 years treated at 243 US hospitals
      participating in CRUSADE from 2003 to 2006, linked to Medicare longitudinal
      claims data (followed to January 1, 2010). Hospital composite adherence examined
      the use of 13 individual American College of Cardiology/American Heart
      Association Class IA guideline-recommended interventions. Among patients who
      survived to hospital discharge, we used Cox proportional hazards modeling to
      examine the association between hospital composite adherence and 1- and 3-year
      mortality conditional on surviving initial hospitalization and adjusting for
      patient baseline clinical factors and hospital characteristics. RESULTS: The
      overall median composite guideline adherence to all 13 interventions was 77.4%
      with median (25th, 75th percentiles) hospital adherence ranging from 66.7%
      (61.9%, 70.1%) in the lowest adherence quartile to 85.8% (83.7%, 88.7%) in the
      highest adherence quartiles. Overall survival at 1 and 3 years was 80.0% and
      62.8%, respectively. Relative to patients treated at the lowest adherence
      hospitals, those treated at the highest had similar adjusted mortality risk at 1
      year but significantly lower 3-year mortality risk (adjusted hazard ratio [95%
      CI] 0.90 [0.82-0.99]). For every 10% increase in adherence to all 13 hospital
      composite therapies, there was a 5% reduction in 3-year mortality risk (0.95
      [0.91-0.98]). CONCLUSIONS: Use of guideline-based therapies during acute
      hospitalization for NSTEMI was associated with significant decreases in mortality
      up to 3 years post-hospital discharge.

PMID- 26299225
TI  - A validated risk model for 1-year mortality after primary prevention implantable
      cardioverter defibrillator placement.
AB  - OBJECTIVE: We sought to determine survival for patients with heart failure after
      an implantation of an implantable cardioverter defibrillator (ICD) for primary
      prevention in the United States and to develop a simple model that would predict
      mortality risk. BACKGROUND: Clinical trials have found that patients with heart
      failure with a 1-year mortality risk near 20% may not benefit from an ICD.
      METHODS: We identified patients from the ICD Registry of the National
      Cardiovascular Disease Registries who underwent ICD implantation for primary
      prevention from 2007 to 2009. Two risk scores for mortality were developed in 2
      cohorts: one limited to those with a B-type natriuretic peptide (BNP) value and a
      second for all patients. The scores were obtained from derivation datasets and
      tested in a validation sets using logistic regression models and classification
      and regression trees. RESULTS: In a primary prevention population with BNP
      available (18,725) the 6 variables most predictive of 1-year mortality were age
      >=75, BNP >=700 pg/mL, chronic lung disease, dialysis, blood urea nitrogen >=30
      mg/dL, and systolic blood pressure <120 mmHg. Patients with zero risk factors had
      a 3.3% one-year mortality compared to a 66.7% one-year mortality for those with
      all 6 risk factors. Those with >=3 risk factors (24.0% of the population) had a
      25.8% one-year mortality. A second score using a larger cohort that did not
      consider BNP identified similar risk factors. CONCLUSIONS: A simple validated
      risk score can identify patients at high and low risk for death within a year
      after ICD placement. A large fraction of those currently implanted with an ICD in
      the United States have a high 1-year mortality and may not benefit from ICD
      therapy.

PMID- 26299226
TI  - Predictors of clinical outcomes in acute decompensated heart failure: Acute Study
      of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure outcome
      models.
AB  - BACKGROUND: Patients hospitalized for acute decompensated heart failure (ADHF)
      are at high risk for early mortality and rehospitalization. Risk stratification
      of ADHF using clinically available data on admission is increasingly important to
      integrate with clinical pathways. Our goal was to create a simple method of
      screening patients upon admission to identify those with increased risk of future
      adverse events. METHODS: Using ASCEND-HF, a pragmatic clinical trial conducted in
      398 sites globally, we developed and validated logistic regression risk models
      for (a) 30-day mortality/HF rehospitalization, (b) 30-day mortality/all-cause
      rehospitalization, (c) 30-day all-cause mortality, and (d) 180-day all-cause
      mortality. Fifty-one candidate variables were evaluated based on prior
      publications and clinical review. Final models were selected based on stepwise
      selection with entry and a staying criterion of P < .01. The 30-day mortality
      model was externally validated, and coefficients were converted to an additive
      risk score. RESULTS: Among 7,141 patients, the median age was 67 years, 34% were
      female, and 80% had a left ventricular ejection fraction <40%. The models had
      between 5 and 12 risk factors with c-indices ranging from 0.68 to 0.75. A
      simplified score, including age, systolic blood pressure, sodium, blood urea
      nitrogen, and dyspnea at rest, discriminated 30-day mortality risk from 0.5%
      (score 0) to 53% (score 10). CONCLUSIONS: Commonly available clinical variables
      provide simple risk stratification for clinical outcomes among patients with
      ADHF, and these models may be considered for integration into routine clinical
      care.

PMID- 26299227
TI  - Worsening heart failure during hospitalization for acute heart failure: Insights
      from the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated
      Heart Failure (ASCEND-HF).
AB  - BACKGROUND: Despite initial in-hospital treatment of acute heart failure (HF),
      some patients experience worsening HF (WHF). There are limited data about the
      outcomes and characteristics of patients who experience in-hospital WHF. METHODS
      AND RESULTS: We assessed the characteristics and outcomes of patients with and
      without WHF in the ASCEND-HF trial. Worsening HF was defined as at least 1
      symptom or sign of new, persistent, or WHF requiring additional intravenous
      inotropic/vasodilator or mechanical therapy during index hospitalization. We
      assessed the relationship between WHF and 30-day mortality, 30-day mortality or
      HF hospitalization, and 180-day mortality. We also assessed whether there was a
      differential association between early (days 1-3) vs late (day >=4) WHF and
      outcomes. Of 7,141 patients with acute HF, 354 (5%) experienced WHF. Patients
      with WHF were more often male and had a history of atrial fibrillation or
      diabetes, lower blood pressure, and higher creatinine. After risk adjustment, WHF
      was associated with increased 30-day mortality (odds ratio 13.37, 95% CI 9.85
      18.14), 30-day mortality or HF rehospitalization (odds ratio 6.78, 95% CI 5.25
      8.76), and 180-day mortality (hazard ratio 3.90, 95% CI 3.14-4.86) (all P values
      < .0001). There was no evidence of a difference in outcomes between early and
      late WHF (all P values for comparison >= .2). CONCLUSIONS: Worsening HF during
      index hospitalization was associated with worse 30- and 180-day outcomes.
      Worsening HF may represent an important patient-centered outcome in acute HF and
      a focus of future treatments.

PMID- 26299228
TI  - Intermediate and long-term risk of new-onset heart failure after hospitalization
      for pneumonia in elderly adults.
AB  - BACKGROUND: Pneumonia is associated with high risk of heart failure (HF) in the
      short term (30 days) postinfection. Whether this association persists beyond this
      period is unknown. METHODS: We studied 5,613 elderly (>=65 years) adults enrolled
      in the Cardiovascular Health Study between 1989 and 1994 at 4 US communities.
      Participants had no clinical diagnosis of HF at enrollment, and they were
      followed up through December 2010. Hospitalizations for pneumonia were identified
      using validated International Classification of Disease Ninth Revision codes. A
      centralized committee adjudicated new-onset HF events. Using Cox regression, we
      estimated adjusted hazard ratios (HRs) of new-onset HF at different time
      intervals after hospitalization for pneumonia. RESULTS: A total of 652
      participants hospitalized for pneumonia during follow-up were still alive and
      free of clinical diagnosis of HF by day 30 posthospitalization. Relative to the
      time of their hospitalization, new-onset HF occurred in 22 cases between 31 and
      90 days (HR 6.9, 95% CI 4.46-10.63, P < .001), 14 cases between 91 days and 6
      months (HR 3.2, 95% CI 1.88-5.50, P < .001), 20 cases between 6 months and 1 year
      (HR 2.6, 95% CI 1.64-4.04, P < .001), 76 cases between 1 and 5 years (HR 1.7, 95%
      CI 1.30-2.12, P < .001), and 71 cases after 5 years (HR 2.0, 95% CI 1.56-2.58, P
      < .001). Results were robust to sensitivity analyses using stringent definitions
      of pneumonia and extreme assumptions for potential informative censoring.
      CONCLUSION: Hospitalization for pneumonia is associated with increased risk of
      new-onset HF in the intermediate and long term. Studies should characterize the
      mechanisms of this association in order to prevent HF in elderly pneumonia
      survivors.

PMID- 26299229
TI  - Diuretic response in acute heart failure-an analysis from ASCEND-HF.
AB  - BACKGROUND: Diuretic unresponsiveness often occurs during hospital admission for
      acute heart failure (AHF) and is associated with adverse outcome. This study aims
      to investigate determinants, clinical outcome, and the effects of nesiritide on
      diuretic response early after admission for AHF. METHODS: Diuretic response,
      defined as weight loss per 40 mg of furosemide or equivalent, was examined from
      hospital admission to 48 hours in 4,379 patients from the ASCEND-HF trial. As an
      additional analysis, a urinary diuretic response metric was investigated in 5,268
      patients using urine volume from hospital admission to 24 hours per 40 mg of
      furosemide or equivalent. RESULTS: Mean diuretic response was -0.42 kg/40 mg of
      furosemide (interquartile range -1.0, -0.05). Poor responders had lower blood
      pressure, more frequent diabetes, long-term use of loop diuretics, poorer
      baseline renal function, and lower urine output (all P < .01). Randomized
      nesiritide treatment was not associated with diuretic response (P = .987). Good
      diuretic response was independently associated with a significantly decreased
      risk of 30-day all-cause mortality or heart failure rehospitalization (odds ratio
      0.44, 95% CI 0.29-0.65, highest vs lowest quintile, P < .001). Diuretic response
      based on urine output per 40 mg of furosemide showed similar results in terms of
      clinical predictors, association with outcome, and the absence of an effect of
      nesiritide. CONCLUSIONS: Poor diuretic response early after hospital admission
      for AHF is associated with low blood pressure, renal impairment, low urine
      output, and an increased risk of death or rehospitalization early after
      discharge. Nesiritide had a neutral effect on diuretic response.

PMID- 26299230
TI  - Race and ethnicity influences on cardiovascular and renal events in patients with
      diabetes mellitus.
AB  - BACKGROUND: The incidence of end-stage renal disease (ESRD) has been consistently
      shown to be higher among blacks and Hispanics compared to whites with unmeasured
      risk factors and access to care as suggested explanations. In a high-risk cohort
      with frequent protocol-directed follow-up, we evaluated the influence of race on
      cardiovascular (CV) outcomes and incidence of ESRD. METHODS: TREAT was a
      randomized, double-blind, placebo-controlled study. This secondary analysis
      focused on role of race on outcomes. TREAT enrolled 4,038 patients with type 2
      diabetes, chronic kidney disease (estimated glomerular filtration rate 20-60
      mL/min per 1.73 m(2)), and anemia (hemoglobin level <=11 g/dL) treated with
      either darbepoetin alfa or placebo. We compared self-described black and Hispanic
      patients to white patients with regard to baseline characteristics and outcomes,
      including mortality, CV outcomes (myocardial infarction, stroke, heart failure,
      resuscitated sudden death, and coronary revascularization), and incident ESRD.
      Multivariate adjusted Cox models were developed for these outcomes. RESULTS:
      Black and Hispanic patients were younger, more likely women, had less prior CV
      disease, and higher blood pressure. During a mean follow-up of 2.4 years with
      comparable access to care, blacks and Hispanics had a greater risk of ESRD but a
      significant lower risk of myocardial infarction and coronary revascularization
      than whites. After adjusting for confounders, blacks remained at significantly
      greater risk of ESRD than whites (hazard ratio 1.53, 95% CI 1.26-1.85, P < .001),
      whereas this ESRD risk did not persist among Hispanics. CONCLUSION: Despite
      similar access to care and lower CV event rates, the risk of ESRD was higher
      among blacks and Hispanics than whites. For blacks, but not Hispanics, this
      increase was independent of known attributable risk factors.

PMID- 26299231
TI  - Gender and outcomes after primary prevention implantable cardioverter
      defibrillator implantation: Findings from the National Cardiovascular Data
      Registry (NCDR).
AB  - BACKGROUND: Clinical trials have demonstrated the benefit of implantable
      cardioverter-defibrillators (ICDs) for the primary prevention of sudden cardiac
      death in selected high-risk individuals. Because of small numbers of women
      enrolled in these trials, outcomes for women after hospital discharge have not
      been well described. We compared procedure-related complications and outcomes
      after hospital discharge between men and women undergoing single- or dual-chamber
      ICD implantation for primary prevention. METHODS: In patients 65 years or older
      with Medicare fee-for-service coverage, we identified 38,912 initial implants
      (25% women) who received single- or dual-chamber ICDs for primary prevention
      between January 2006 and December 2009 in the NCDR and evaluated gender
      differences in outcomes. RESULTS: Women had greater comorbidity and more advanced
      heart failure (HF) at the time of ICD implantation than did men. Device-related
      complications, death at 6 months, all-cause readmissions, and HF readmissions at
      6 months were significantly more common in women (7.2% vs 4.8%, 6.5% vs 5.6%,
      37.2% vs 31.7%, and 14.0% vs 10.0% respectively; P < .001 for all). Women
      continued to have higher odds of procedural complications (odds ratio [OR] 1.39,
      95% CI 1.26-1.53, P < .001), 6-month all-cause readmission (OR 1.22, 95% CI 1.16
      1.28, P < .001), and 6-month HF readmission (OR 1.32, 95% CI 1.23-1.42, P <
      .001), with a trend toward higher 6-month mortality (OR 1.08, 95% CI 0.98-1.20, P
      = .123), compared with men, after adjusting for differences in baseline
      characteristics and device type (single vs dual chamber). CONCLUSIONS: Among
      older patients receiving ICDs for primary prevention in clinical practice, women
      experience worse outcomes than do men. Reasons for gender differences in outcomes
      are poorly understood and require further investigation.

PMID- 26299232
TI  - Survival from sports-related sudden cardiac arrest: In sports facilities versus
      outside of sports facilities.
AB  - BACKGROUND: We sought to evaluate frequency, characteristics, and outcomes of
      sudden cardiac arrest (SCA) during sports activities according to the location of
      occurrence (in sports facilities vs those occurring outside of sports
      facilities). METHODS AND RESULTS: This is an observational 5-year prospective
      national French survey of subjects 10 to 75 years old presenting with SCA during
      sports (2005-2010), in 60 French administrative regions (covering a population of
      35 million people). Of the 820 SCA during sports, 426 SCAs (52%) occurred in
      sports facilities. Overall, a substantially higher survival rate at hospital
      discharge was observed among SCA in sports facilities (22.8%, 95% CI 18.8-26.8)
      compared to those occurring outside (8.0%, 95% CI 5.3-10.7) (P < .0001). Patients
      with SCA in sports facilities were younger (42.1 vs 51.3 years, P < .0001) and
      less frequently had known cardiovascular diseases (P < .0001). The events were
      more often witnessed (99.8% vs 84.9%, 0.0001), and bystander cardiopulmonary
      resuscitation was more frequently initiated (35.4% vs 25.9%, P = .003). Delays of
      intervention were significantly shorter when SCA occurred in sports facilities
      (9.3 vs 13.6, P=0.03), and the proportion of initially shockable rhythm was
      higher (58.8% vs 33.1%, P < .0001). Better survival in sports facilities was
      mainly explained by concomitant circumstances of occurrence (adjusted odds ratio
      1.48, 95% CI 0.88-2.49, P = .134). CONCLUSIONS: Sports-related SCA is not a
      homogeneous entity. The 3-fold higher survival rate reported among sports-related
      SCA is mainly due to cases that occur in sports facilities, whereas SCA during
      sports occurring outside of sports facilities has the usual very low rate of
      survival.

PMID- 26299233
TI  - Evaluation of Selvester QRS score for use in presence of conduction abnormalities
      in a broad population.
AB  - BACKGROUND: The Selvester QRS score is an electrocardiographic tool designed to
      quantify myocardial scar. It was updated in 2009 to expand its usefulness in
      patients with conduction abnormalities such as bundle-branch and fascicular
      blocks. There is need to further validate the updated score in a broader group of
      patients with cardiovascular disease and conduction abnormalities. We primarily
      hypothesized that the updated score could distinguish between presence and
      absence of scar by cardiac magnetic resonance imaging (CMR) with late gadolinium
      enhancement in 4 groups of patients with distinct conduction abnormalitites.
      METHODS: A total of 193 patients were retrospectively identified that had
      received an electrocardiogram (ECG) and a CMR scan at Duke University Medical
      Center between January 2011 and August 2013: 62 with left bundle-branch block, 51
      with right bundle-branch block (RBBB), 43 with left anterior fascicular block
      (LAFB), and 37 with RBBB + LAFB. Scar sizes estimated by ECG and by CMR were
      compared using scatterplots, modified Bland-Altman plots, and receiver operating
      characteristics curves. RESULTS: Of 193 patients, 96 (50%) had no scar by CMR.
      The QRS score generally overestimated CMR scar. The area under the curve ranged
      between 0.62 and 0.65 for the different conduction types, and 95% confidence
      intervals included 0.5 for all conduction types. Performance was slightly
      improved in LAFB and RBBB + LAFB by excluding all points derived from leads V4
      V6. CONCLUSIONS: The Selvester QRS score for use in conduction abnormalities
      needs to be improved, primarily its specificity, to enable effective clinical use
      in a population with a wide range of left ventricular ejection fraction and low
      pretest probability of myocardial scar.

PMID- 26299234
TI  - Impact of access site choice on outcomes of patients with cardiogenic shock
      undergoing percutaneous coronary intervention: A systematic review and meta
      analysis.
AB  - BACKGROUND: The benefit of transradial access (TRA) in patients with cardiogenic
      shock (CS) is uncertain. We sought to determine the benefits of TRA in patients
      with CS undergoing coronary angiography/intervention. METHODS: MEDLINE, Embase,
      Cochrane Central, and electronic databases were searched for studies that
      assessed the following: (1) patients with CS who underwent percutaneous coronary
      intervention (PCI) and (2) the association between choice of arterial access, 30
      day all-cause mortality, and 30-day major adverse cardiac and cerebral events
      (MACCEs) using random-effects model. RESULTS: From 3,652 retrieved citations, 8
      studies involving 8,131 patients with CS undergoing PCI (via TRA: 2,321 patients,
      via TFA: 5,810 patients) were included. Transradial access was associated with
      significantly reduced risk for all-cause mortality (unadjusted: risk ratio [RR]
      0.60, 95% CI 0.52-0.71, P < .001, I(2) = 29%, 8 included studies; adjusted: RR
      0.55, 95% CI 0.46-0.65, P < .001, I(2) = 0%, 6 included studies) and MACCE
      (unadjusted: RR 0.68, 95% CI 0.63-0.73, P < .001, I(2) = 0%, 6 included studies;
      adjusted: RR 0.63, 95% CI 0.52-0.75, P < .001, I(2) = 0%, 4 included studies) at
      30 days when compared with TFA. CONCLUSIONS: Transradial access is associated
      with reduced mortality and MACCE at 30 days in patients with CS undergoing PCI.
      Considering the possible influence of selection bias on the effect estimate in
      our analysis, randomized controlled trials are needed to better assess this
      association.

PMID- 26299235
TI  - Cardiovascular mortality prediction in veterans with arm exercise vs
      pharmacologic myocardial perfusion imaging.
AB  - BACKGROUND: No data exist comparing outcome prediction from arm exercise vs
      pharmacologic myocardial perfusion imaging (MPI) stress test variables in
      patients unable to perform treadmill exercise. METHODS: In this retrospective
      study, 2,173 consecutive lower extremity disabled veterans aged 65.4 +/-
      11.0years (mean +/- SD) underwent either pharmacologic MPI (1730 patients) or arm
      exercise stress tests (443 patients) with MPI (n = 253) or electrocardiography
      alone (n = 190) between 1997 and 2002. Cox multivariate regression models and
      reclassification analysis by integrated discrimination improvement (IDI) were
      used to characterize stress test and MPI predictors of cardiovascular mortality
      at >=10-year follow-up after inclusion of significant demographic, clinical, and
      other variables. RESULTS: Cardiovascular death occurred in 561 pharmacologic MPI
      and 102 arm exercise participants. Multivariate-adjusted cardiovascular mortality
      was predicted by arm exercise resting metabolic equivalents (hazard ratio [HR]
      0.52, 95% CI 0.39-0.69, P < .001), 1-minute heart rate recovery (HR 0.61, 95% CI
      0.44-0.86, P < .001), and pharmacologic and arm exercise delta (peak-rest) heart
      rate (both P < .001). Only an abnormal arm exercise MPI prognosticated
      cardiovascular death by multivariate Cox analysis (HR 1.98, 95% CI 1.04-3.77, P <
      .05). Arm exercise MPI defect number, type, and size provided IDI over covariates
      for prediction of cardiovascular mortality (IDI = 0.074-0.097). Only
      pharmacologic defect size prognosticated cardiovascular mortality (IDI = 0.022).
      CONCLUSIONS: Arm exercise capacity, heart rate recovery, and pharmacologic and
      arm exercise heart rate responses are robust predictors of cardiovascular
      mortality. Arm exercise MPI results are equivalent and possibly superior to
      pharmacologic MPI for cardiovascular mortality prediction in patients unable to
      perform treadmill exercise.

PMID- 26299236
TI  - Comparison of quality-of-life measures after radial versus femoral artery access
      for cardiac catheterization in women: Results of the Study of Access Site for
      Enhancement of Percutaneous Coronary Intervention for Women quality-of-life
      substudy.
AB  - BACKGROUND: In the SAFE-PCI for Women trial, patient preference for radial access
      for future procedures was greater than for femoral access. We sought to assess
      whether radial or femoral access impacts formal measures of quality-of-life (QOL)
      among women undergoing cardiac catheterization. METHODS: We assessed QOL using
      European quality of life-5 dimensions (EQ-5D) and EQ visual analog scale (EQ-VAS)
      scores among 304 women randomized to radial or femoral arteriotomy in the SAFE
      PCI for Women trial at sites with QOL substudy approval. Patient surveys were
      administered at baseline, hospital discharge, and 30 days (for percutaneous
      coronary intervention patients). RESULTS: Women randomized to both treatments had
      similar EQ-5D index and EQ-VAS scores at baseline, hospital discharge, and 30-day
      follow-up. After adjustment for baseline scores, there was no effect of assigned
      treatment on EQ-5D (discharge 0.004; 95% CI -0.03 to 0.04; 30 days -0.03; 95% CI 
      0.09 to 0.02) or EQ-VAS (discharge -1.31; 95% CI -4.74 to 2.12; 30 days -2.10;
      95% CI -8.92 to 4.71) scores. At discharge, 60.5% versus 63.5% (P = .60) of
      patients in radial and femoral groups were free from access site pain; at 30
      days, rates were 85.7% versus 77.6% (P = .30), respectively. Patient preference
      for the same access strategy for repeat procedures was greater in the radial
      versus femoral group (77.2% vs 26.8%; P < .0001). CONCLUSIONS: Using established
      QOL instruments, we did not measure any difference in QOL or functional status
      according to access site strategy in women undergoing cardiac catheterization,
      yet patient preference for the radial approach was significantly greater. Other
      factors influencing patient choice for radial access should be investigated.

PMID- 26299237
TI  - Six-year change in high-sensitivity C-reactive protein and risk of diabetes,
      cardiovascular disease, and mortality.
AB  - BACKGROUND: Single measurements of elevated high-sensitivity C-reactive protein
      (hs-CRP) are associated with increased risk of diabetes, cardiovascular disease,
      and mortality. Large increases or sustained elevations in hs-CRP may be
      associated with even greater risk of these outcomes. The objective of this study
      was to characterize the association of 6-year change in hs-CRP with incident
      diabetes, incident cardiovascular events (heart disease, stroke, and heart
      failure), and mortality. METHODS: We included 10,160 ARIC participants with hs
      CRP measured at visits 2 (1990-1992) and 4 (1996-1998). Change in hs-CRP was
      categorized as sustained low/moderate (<3 mg/L at both visits), decreased (>=3
      mg/L at visit 2 and <3 mg/L at visit 4), increased (<3 mg/L at visit 2 and >=3
      mg/L at visit 4), and sustained elevated (>=3 mg/L at both visits). Cox
      proportional hazards models were used to assess the association of 6-year change
      in hs-CRP with incident diabetes, cardiovascular events, and death during ~15
      years after visit 4. RESULTS: Compared with persons with sustained low/moderate
      hs-CRP, those with increased or sustained elevated hs-CRP had an increased risk
      of incident diabetes (hazard ratios [95% CIs] 1.56 [1.38-1.76] and 1.39 [1.25
      1.56], respectively), whereas those with deceased hs-CRP did not. Persons with
      sustained elevated hs-CRP had an increased risk of coronary heart disease,
      ischemic stroke, heart failure, and mortality (hazard ratios [95% CIs] 1.51 [1.23
      1.85], 1.70 [1.32-2.20], 1.60 [1.35-1.89], and 1.52 [1.37-1.69], respectively)
      compared with those with sustained low/moderate hs-CRP. Associations for
      sustained elevated hs-CRP were greater than for those with increased hs-CRP over
      6 years. CONCLUSIONS: Large increases or sustained elevations in hs-CRP over a 6
      year period were associated with a subsequent increased risk of diabetes, and
      persons with sustained elevations in hs-CRP were at the highest risk for
      cardiovascular disease and mortality. Two measurements of hs-CRP are better than
      one for characterizing risk, and large increases are particularly prognostic.

PMID- 26299238
TI  - Cardiorespiratory fitness attenuates risk for major adverse cardiac events in
      hyperlipidemic men and women independent of statin therapy: The Henry Ford
      ExercIse Testing Project.
AB  - AIMS: We sought to evaluate the effect of cardiorespiratory fitness (CRF) in
      predicting mortality, myocardial infarction (MI), and revascularization in
      patients with hyperlipidemia after stratification by gender and statin therapy.
      METHODS AND RESULTS: This retrospective cohort study included 33,204 patients
      with hyperlipidemia (57 +/- 12 years old, 56% men, 25% black) who underwent
      physician-referred treadmill stress testing at the Henry Ford Health System from
      1991 to 2009. Patients were stratified by gender, baseline statin therapy, and
      estimated metabolic equivalents from stress testing. We computed hazard ratios
      using Cox regression models after adjusting for demographics, cardiac risk
      factors, comorbidities, pertinent medications, interaction terms, and indication
      for stress testing. RESULTS: There were 4,851 deaths, 1,962 MIs, and 2,686
      revascularizations over a median follow-up of 10.3 years. In men and women not on
      statin therapy and men and women on statin therapy, each 1-metabolic equivalent
      increment in CRF was associated with hazard ratios of 0.86 (95% CI 0.85-0.88),
      0.83 (95% CI 0.81-0.85), 0.85 (95% CI 0.83-0.87), and 0.84 (95% CI 0.81-0.87) for
      mortality; 0.93 (95% CI 0.90-0.96), 0.87 (95% CI 0.83-0.91), 0.89 (95% CI 0.86
      0.92), and 0.90 (95% CI 0.86-0.95) for MI; and 0.91 (95% CI 0.88-0.93), 0.87 (95%
      CI 0.83-0.91), 0.89 (95% CI 0.87-0.92), and 0.90 (95% CI 0.86-0.94) for
      revascularization, respectively. No significant interactions were observed
      between CRF and statin therapy (P > .23). CONCLUSION: Higher CRF attenuated risk
      for mortality, MI, and revascularization independent of gender and statin therapy
      in patients with hyperlipidemia. These results reinforce the prognostic value of
      CRF and support greater promotion of CRF in this patient population.

PMID- 26299239
TI  - Anatomic runoff score predicts cardiovascular outcomes in patients with lower
      extremity peripheral artery disease undergoing revascularization.
AB  - BACKGROUND: Although the presence, extent, and severity of obstruction in
      patients with lower extremity peripheral artery disease (LE PAD) affect their
      functional status, quality of life, and treatment, it is not known if these
      factors are associated with future cardiovascular events. We empirically created
      an anatomic runoff score (ARS) to approximate the burden of LE PAD and determined
      its association with clinical outcomes. METHODS: We evaluated all patients with
      LE PAD and bilateral angiography undergoing revascularization in a community
      based clinical study. Primary clinical outcomes of interest were (1) a composite
      of all-cause death, myocardial infarction (MI), and stroke and (2) amputation
      free survival. Cox proportional hazards models were created to identify
      predictors of clinical outcomes. RESULTS: We evaluated 908 patients undergoing
      angiography, and a total of 260 (28.0%) patients reached the composite end point
      (45 MI, 63 stroke, and 152 death) during the study period. Anatomic runoff score
      ranged from 0 to 15 (mean 4.7; SD 2.5) with higher scores indicating a higher
      burden of disease, and an optimal cutpoint analysis classified patients into low
      ARS (<5) and high ARS (>=5). The unadjusted rates of the primary composite end
      point and amputation-free survival were nearly 2-fold higher in patients with a
      high ARS when compared with patients with a low ARS. The most significant
      predictors of the composite end point (death/MI/stroke) were age (delta 10 years;
      hazard ratio [HR] 1.53; CI 1.32-1.78; P < .001), diabetes mellitus (HR 1.65; CI
      1.26-2.18; P < .001), glomerular filtration rate <30 (HR 2.23; CI 1.44-3.44; P <
      .001), statin use (HR 0.66; CI 0.48-0.88; P < .001), and ARS (delta 2 points; HR
      1.21; CI 1.08-1.35; P < .001). CONCLUSIONS: After adjustment for clinical
      factors, the LE PAD ARS was an independent predictor of future cardiovascular
      morbidity and mortality in a broadly representative patient population undergoing
      revascularization for symptomatic PAD. A clinically useful anatomic scoring
      system, if validated, may assist clinicians in risk stratification during the
      course of clinical decision making.

PMID- 26299240
TI  - Ultraslow thrombolytic therapy: A novel strategy in the management of PROsthetic
      MEchanical valve Thrombosis and the prEdictors of outcomE: The Ultra-slow
      PROMETEE trial.
AB  - BACKGROUND: Low-dose (25mg), slow infusion (6hours) of tissue-type plasminogen
      activator (t-PA) with repetition as needed has been shown to provide effective
      and safer thrombolysis in patients with prosthetic valve thrombosis (PVT).
      Further prolonging the infusion time may be rational with regard to reducing
      complication rates without reducing success rates. We aimed to investigate the
      efficacy and safety of ultraslow (25hours) infusion of low-dose (25mg) alteplase
      (t-PA) for PVT. METHODS AND RESULTS: Transesophageal echocardiography-guided
      thrombolytic therapy (TT) was administered to 114 patients with PVT in 120
      different episodes between 2009 and 2013 in a single center. Prosthetic valve
      thrombosis was obstructive in 77 (64.2%) and nonobstructive in 43 (35.8%)
      episodes. Ultraslow infusion (25hours) of low-dose (25mg) t-PA, as the TT
      regimen, was used in all patients admitted with PVT. The end points were
      thrombolytic success, mortality, and complication rates. The overall success rate
      of TT was 90% (95% CI 0.85-0.95). The univariate predictors of an unsuccessful
      result were higher New York Heart Association (NYHA) class, thrombus cross
      sectional area, duration of suboptimal anticoagulation, lower baseline valve
      area, and presence of atrial fibrillation. The NYHA class was the only
      independent predictor of TT failure by multiple variable analysis. The overall
      complication rate was 6.7% (3.3% nonfatal major, 2.5% minor, and 0.8% death). The
      predictors of complications were presence of atrial fibrillation, higher NYHA
      class, and thrombus area. CONCLUSION: Ultraslow (25hours) infusion of low-dose
      (25mg) t-PA without bolus appears to be associated with quite low nonfatal
      complications and mortality for PVT patients without loss of effectiveness,
      except for those with NYHA class IV.

PMID- 26299241
TI  - Commentary on "Supervised versus unsupervised exercise for intermittent
      claudication: A sytematic review and meta-analysis".

PMID- 26299242
TI  - Letter response.

PMID- 26299243
TI  - Temporal-spatial pathological changes in the brains of permissive and non
      permissive hosts experimentally infected with Angiostrongylus cantonensis.
AB  - Human cerebral angiostrongyliasis becomes an emerging disease in many parts of
      the world. By postmortem examination, Angiostrongylus cantonensis have been
      reported to cause severe pathological changes in the central nervous system. The
      present study was designed to determine the temporal-spatial pathological changes
      through experimental infections and histopathological examination of permissive
      (SD rats) and non-permissive (ICR mice) hosts. After infecting SD rats with 25,
      50, or 100 third-stage larvae (L3) and ICR mice with 25 L3, one animal from each
      group was sacrificed daily from day 1 to day 30 post-infection. Each rat brain
      was cut into six sections and mouse brain into five sections. These sections were
      stained with haematoxylin and eosin and examined microscopically. Eosinophilic
      meningitis was found to be the most commonly pathological change and occurred on
      day 17 post-infection in rats with 25 L3, day 9 in the 50- or 100-L3 groups, and
      day 12 in infected mice. Thickness of the meninges increased 9-24 folds in
      infected rats and 89 folds in an infected mouse on day 28. Encephalitis,
      congestion, perivascular cuffing, and haemorrhage were revealed in infected mice
      and rats with 100 L3. Fifth-stage larvae were frequently observed in the meninges
      but occasionally in the parenchyma. Significant correlations between meningitis
      and presence of larvae in the meninges were found in the three infected rat
      groups but not in the infected mice. The results indicate that the clinical
      course of A. cantonensis infection is not self-limited but becomes more severe
      with the intensity of infection. 

PMID- 26299244
TI  - Low reduction potential cytochrome b5 isotypes of Giardia intestinalis.
AB  - Despite lacking mitochondria and a known pathway for heme biosynthesis the micro
      aerotolerant anaerobic protozoan parasite Giardia intestinalis encodes four
      members of the cytochrome b5 family of electron transfer proteins, three of which
      are small, single-domain proteins. While these are similar in size and fold to
      their better-known mammalian counterparts the Giardia proteins have distinctly
      lower reduction potentials, ranging from -140 to -171 mV compared to +6 mV for
      the bovine microsomal protein. This difference is accounted for by a more polar
      heme environment in the Giardia proteins, as mutation of a conserved heme pocket
      tyrosine residue to phenylalanine in the Giardia cytochrome b5 isotype-I (gCYTb5
      I Y61F) raises its reduction potential by nearly 100 mV. All three isotypes have
      UV-visible spectra consistent with axial coordination of the heme by a pair of
      histidine residues, but electron paramagnetic spectroscopy indicates that the
      planes of their imidazole rings are nearly perpendicular rather than coplanar as
      observed in mammalian cytochrome b5, which may be due to geometrical constraints
      imposed by a one-residue shorter spacing between the ligand pair in the Giardia
      proteins. Although no function has yet to be ascribed to any Giardia cytochrome
      b5, the presence of similar sequences in many other eukaryotes indicates that
      these represent an under-characterized class of low reduction potential family
      members. 

PMID- 26299245
TI  - Cloning, expression and enzymatic characterization of 3-phosphoglycerate kinase
      from Schistosoma japonicum.
AB  - In the present study, a full-length cDNA encoding the Schistosoma japonicum 3
      phosphoglycerate kinase (SjPGK) with an open reading frame of 1251 bp was
      isolated from 42-day-old (42-d) schistosome cDNAs. Real-time quantitative reverse
      transcription PCR analysis revealed that SjPGK was expressed in all investigated
      developmental stages and at a higher transcript levels in 21- and 42-d worms.
      Moreover, the SjPGK mRNA level was significantly downregulated in 10-d
      schistosomula from Wistar rats (non-susceptible host). SjPGK was subcloned into
      pET28a(+) and expressed as both supernatant and inclusion bodies in Escherichia
      coli BL21 cells. The enzymatic activity of recombinant SjPGK protein (rSjPGK) was
      125 U/mg. Kinetic analyses with respect to 3-phosphoglycerate (3-PGA) as
      substrate gave a Km of 2.69 mmol/L and a Vmax of 748 MUmol/min/mg protein. rSjPGK
      was highly stable over a range of pH 8.0-9.0 and temperature of 30 degrees C-40 
      degrees C under physiological conditions. Immunolocalization analysis showed that
      SjPGK was mainly distributed in the tegument and parenchyma of schistosomes.
      Western blotting showed that rSjPGK had good immunogenicity. We vaccinated BALB/c
      mice with rSjPGK combined with Seppic 206 adjuvant. However, there were no
      significant reductions in the numbers of worms of eggs in the liver, as compared
      to adjuvant or blank control groups in two independent vaccination tests. This
      study provides the basis for further investigations into the biological function
      of SjPGK, although it might not be suitable as a potential vaccine candidate
      against schistosomiasis. 

PMID- 26299246
TI  - Dolichol phosphate mannose synthase from the pathogenic yeast Candida albicans is
      a multimeric enzyme.
AB  - BACKGROUND: Dolichol phosphate mannose synthase (DPMS) is a key enzyme in N- and
      O-linked glycosylations and glycosylphosphatidylinositol (GPI)-anchor synthesis.
      DPMS generates DPM, the substrate for mentioned processes, by the transfer of
      mannosyl residue from GDP-Man to dolichol phosphate. Here we describe the role of
      DPMS for Candida albicans physiology with emphasis on the cell wall composition
      and morphogenesis. METHODS: C. albicans genes for DPMS subunits were cloned,
      tagged and expressed in Saccharomyces cerevisiae. The C. albicans strains with
      controlled expression of DPM genes were constructed and analyzed. Gene expression
      and enzyme activities were measured using RT-PCR and radioactive substrate.
      Sensitivities against chemical agents were tested with microdilution method. The
      composition of the cell wall was estimated by HPLC. Glycosylation status of the
      marker protein was analyzed by Western blot. Morphological differentiation of the
      strains was checked on the media promoting hyphae and chlamydospore formation.
      RESULTS: We demonstrate that C. albicans DPMS consists of three interacting
      subunits, among which Dpm1 and Dpm3 are indispensable, whereas Dpm2 increases
      enzymatic activity. Lowered expression of DPMS genes results in decreased DPMS
      activity, increased susceptibility to cell wall perturbing agents and in altered
      cell wall composition. Mutants Tetp-DPM1 and Tetp-DPM3 show defective protein
      glycosylation and are impaired in hyphae and chlamydospore formation. MAJOR
      CONCLUSION: DPMS from C. albicans, opposite to S. cerevisiae, belongs to the
      family of DPMS with multimeric protein structure. GENERAL SIGNIFICANCE: This work
      provides important data about factors required for a proper protein glycosylation
      and for morphogenesis of pathogenic yeast C. albicans.

PMID- 26299247
TI  - Role of P2X7 receptor in Clostridium perfringens beta-toxin-mediated cellular
      injury.
AB  - BACKGROUND: Clostridium perfringens beta-toxin is a pore-forming toxin (PFT) and
      an important agent of necrotic enteritis and enterotoxemia. We recently reported
      that beta-toxin strongly induced cell death in THP-1 cells via the formation of
      oligomers. We here describe that the P2X(7) receptor, which is an ATP receptor,
      interacts with beta-toxin. METHODS: We tested the role of P2X(7) receptor in beta
      toxin-induced toxicity using specific inhibitors, knockdown of receptor,
      expression of the receptor and interaction by dot-blot assay. The potency of
      P2X(7) receptor was further determined using an in vivo mouse model. RESULTS:
      Selective P2X(7) receptor antagonists (oxidized ATP (o-ATP), oxidized ADP, and
      Brilliant Blue G (BBG)) inhibited beta-toxin-induced cytotoxicity in THP-1 cells.
      o-ATP also blocked the binding of beta-toxin to cells. The P2X(7) receptor and
      beta-toxin oligomer were localized in the lipid rafts of THP-1 cells. siRNA for
      the P2X(7) receptor inhibited toxin-induced cytotoxicity and binding of the
      toxin. In contrast, the siRNA knockdown of P2Y(2) or P2Y(6) had no effect on beta
      toxin-induced cytotoxicity. The addition of beta-toxin to P2X(7)-transfected HEK
      293 cells resulted in binding of beta-toxin oligomer. Moreover, beta-toxin
      specifically bound to immobilized P2X(7) receptors in vitro and colocalized with
      the P2X(7) receptor on the THP-1 cell surface. Furthermore, beta-toxin-induced
      lethality in mice was blocked by the preadministration of BBG. CONCLUSIONS: The
      results of this study indicate that the P2X(7) receptor plays a role in beta
      toxin-mediated cellular injury. GENERAL SIGNIFICANCE: P2X(7) receptor is a
      potential target for the treatment of C. perfringens type C infection.

PMID- 26299248
TI  - Serial pharmacological prescribing practices for tic management in Tourette
      syndrome.
AB  - Pharmacological treatments for Tourette syndrome (TS) vary in efficacy between
      different patients. The evidence base is limited as even high quality controlled
      studies tend to be of relatively short duration which may lose relevance in
      clinical usage. Patients are frequently treated with serial agents in the search
      for efficacy and tolerability. The success of this strategy has not been
      previously documented. We examined 400 consecutive TS patients seen over a 10
      year period, some with a longer prior history in other clinics; 255/400 (64%)
      were prescribed medication. We present this heterogeneous cohort in terms of the
      number of drugs they had tried, and as a proxy measure of some benefit of the
      last drug used, whether it had been prescribed under our supervision for >= 5
      months. The most commonly prescribed medications were aripiprazole (64%),
      clonidine (40%), risperidone (30%) and sulpiride (29%) with changes in
      prescribing practises over the period examined. The number of different drugs
      tried were one (n = 155), two (n = 69), three (n = 36), four (n = 14), five (n =
      15), six (n = 5), seven (n = 2) and eight (n = 1). The data illustrate the
      difficulty in drug treatment of tics and suggest that even after trials of
      several agents there is potential benefit in trying further options.

PMID- 26299249
TI  - Transplantation of a horseshoe kidney from a living donor: Case report, long term
      outcome and donor safety.
AB  - INTRODUCTION: The use of a horseshoe kidney in renal transplant remains
      controversial, when it is found in the evaluation of a living donor, anatomical,
      surgical and ethical issues are involved. PRESENTATION OF CASE: An uncomplicated
      horseshoe kidney was detected in a 51-year-old woman who was the only suitable
      donor for her 30-year-old son. Kidneys were fused in the inferior pole and no
      vascular or urinary abnormalities were detected during imaging evaluation. The
      surgical procedure was approved by the hospital transplant committee. A
      laparotomy was performed by means of a medial upper incision. The isthmus of the
      kidney was divided using a harmonic scalpel and the left segment was used; it had
      2 arteries too distant to create a common one, thus anastomosed separately. The
      renal vein was side-to-side anastomosed to the right external iliac vein and a
      Lich-Gregoir ureteral implant was made. There were no intraoperative or
      postoperative complications in the donor who currently remains asymptomatic.
      Recipient developed a delayed graft function (DGF), and was discharged on the
      12th day after surgery. After 24 months of surgery, renal function has remained
      stable with a serum creatinine of 128MUmol/L (1.45mg/dL). DISCUSSION: There are 7
      reports of a horseshoe kidney from living donors in 8 patients without morbidity
      and a good long term outcome of all recipients. CONCLUSION: If we anticipate a
      low operative risk and there is a suitable anatomy, we may consider the use of
      horseshoe kidneys from living donors a viable alternative.

PMID- 26299250
TI  - Delayed presentation of a metastatic choroidal melanoma to the liver: The latency
      of an elective metastatic localization.
AB  - INTRODUCTION: Choroidal melanoma is the most common primary intraocular malignant
      tumour and the second most common type of primary malignant melanoma in the body.
      Biologically, cutaneuous and ocular melanoma may be considered different, in
      terms of both metastatic diffusion and metastatic latency. The principal target
      organ for metastasis of the ocular melanoma is the liver.This distinctive
      behaviour is also sustained by different metastatic latency, as some patients
      present with metastatic ocular melanoma several years after the treatment of the
      primary tumor. PRESENTATION OF CASE: A 60 year-old male who had undergone left
      ocular enucleation for choroid melanoma 20 years ago was referred to our
      department with a three months history of diffuse abdominal pain, fever, weight
      loss and massive ascites. Abdominal ultrasonography (US) and total body computed
      tomography (CT) scan were performed and revealed diffuse liver metastases,
      associated with peritoneal carcinosis, bilateral adrenal metastases and a large
      mass in the left kidney compatible with another secondary localization. An
      ultrasound guided fine needle agobiopsy (FNA) of liver lesions was performed and
      the pathological findings led to the diagnosis of liver metastasis from choroidal
      melanoma. The patient died a few weeks later for hepatic failure. DISCUSSION:
      Currently, there is no consensus regarding the optimal follow-up in terms of
      screening modality or time interval after the treatment of the primary ocular
      melanoma. CONCLUSION: Patients with gastrointestinal symptoms and a history of
      choroidal melanoma should be investigated for the presence of gastrointestinal or
      liver metastases, although the original primary malignancy was diagnosed years
      before the patient's presentation.

PMID- 26299253
TI  - Impact of Ultrabithorax alternative splicing on Drosophila embryonic nervous
      system development.
AB  - Hox genes control divergent segment identities along the anteroposterior body
      axis of bilateral animals by regulating a large number of processes in a cell
      context-specific manner. How Hox proteins achieve this functional diversity is a
      long-standing question in developmental biology. In this study we investigate the
      role of alternative splicing in functional specificity of the Drosophila Hox gene
      Ultrabithorax (Ubx). We focus specifically on the embryonic central nervous
      system (CNS) and provide a description of temporal expression patterns of three
      major Ubx isoforms during development of this tissue. These analyses imply
      distinct functions for individual isoforms in different stages of neural
      development. We also examine the set of Ubx isoforms expressed in two isoform
      specific Ubx mutant strains and analyze for the first time the effects of
      splicing defects on regional neural stem cell (neuroblast) identity. Our findings
      support the notion of specific isoforms having different effects in providing
      individual neuroblasts with positional identity along the anteroposterior body
      axis, as well as being involved in regulation of progeny cell fate. 

PMID- 26299252
TI  - Loss of lamin A function increases chromatin dynamics in the nuclear interior.
AB  - Chromatin is organized in a highly ordered yet dynamic manner in the cell
      nucleus, but the principles governing this organization remain unclear.
      Similarly, it is unknown whether, and how, various proteins regulate chromatin
      motion and as a result influence nuclear organization. Here by studying the
      dynamics of different genomic regions in the nucleus of live cells, we show that
      the genome has highly constrained dynamics. Interestingly, depletion of lamin A
      strikingly alters genome dynamics, inducing a dramatic transition from slow
      anomalous diffusion to fast and normal diffusion. In contrast, depletion of
      LAP2alpha, a protein that interacts with lamin A and chromatin, has no such
      effect on genome dynamics. We speculate that chromosomal inter-chain interactions
      formed by lamin A throughout the nucleus contribute to chromatin dynamics, and
      suggest that the molecular regulation of chromatin diffusion by lamin A in the
      nuclear interior is critical for the maintenance of genome organization. 

PMID- 26299251
TI  - Methamphetamine Use in HIV-infected Individuals Affects T-cell Function and Viral
      Outcome during Suppressive Antiretroviral Therapy.
AB  - We investigated the associations between methamphetamine (meth) use, immune
      function, and the dynamics of HIV and cytomegalovirus [CMV] in the blood and
      genital tract of HIV-infected ART-suppressed subjects. Self-reported meth use was
      associated with increased CD4(+) and CD8(+) T-cell proliferation (Ki67(+), p <
      0.005), CD4(+) T-cell activation (CD45RA(-)CD38(+), p = 0.005) and exhaustion (PD
      1(+), p = 0.0004) in blood, compared to non-meth users. Meth use was also
      associated with a trend towards higher blood HIV DNA levels (p = 0.09) and more
      frequent shedding of CMV in seminal plasma (p = 0.002). To explore possible
      mechanisms, we compared ex vivo spontaneous and antigen-specific proliferation in
      PBMC collected from subjects with and without positive meth detection in urine
      (Utox+ vs. Utox-). Despite higher levels of spontaneous proliferation,
      lymphocytes from Utox+ meth users had a significantly lower proliferative
      capacity after stimulation with a number of pathogens (CMV, candida,
      mycobacterium, toxoplasma, HIV, p < 0.04 in all cases), compared to Utox-
      participants. Our findings suggest that meth users have greater proliferation and
      exhaustion of the immune system. Meth use is also associated with a loss of
      control of CMV replication, which could be related to loss of immune response to
      pathogens. Future studies should consider meth use as a potential modulator of T
      cell responses. 

PMID- 26299254
TI  - Critical role for Fat/Hippo and IIS/Akt pathways downstream of Ultrabithorax
      during haltere specification in Drosophila.
AB  - In Drosophila, differential development of wing and haltere, which differ in cell
      size, number and morphology, is dependent on the function of Hox gene
      Ultrabithorax (Ubx). Here we report our studies on Ubx-mediated regulation of the
      Fat/Hippo and IIS/dAkt pathways, which control cell number and cell size during
      development. Over-expression of Yki or down regulation of negative components of
      the Fat/Hippo pathway, such as expanded, caused considerable increase in haltere
      size, mainly due to increase in cell number. These phenotypes were also
      associated with the activation of Akt pathways in developing haltere. Although
      activation of Akt alone did not affect the cell size or the organ size, we
      observed dramatic increase in haltere size when Akt was activated in the
      background where expanded is down regulated. This was associated with the
      increase in both cell size and cell number. The organ appeared flatter than
      wildtype haltere and the trichome morphology and spacing resembled that of wing
      suggesting homeotic transformations. Thus, our results suggest a link between
      cellular growth and pattern formation and the final differentiated state of the
      organ. 

PMID- 26299255
TI  - Steroidal glycoalkaloids: chemical defence of edible African nightshades against
      the tomato red spider mite, Tetranychus evansi (Acari: Tetranychidae).
AB  - BACKGROUND: Tetranychus evansi is an invasive pest of solanaceous crops in
      Africa, and in the field it differentially attacks edible African nightshades.
      The chemical basis for the differential attack on these plant species is largely
      unknown. Using bioassays and chemical analysis, we investigated the differential
      bioactivity of leaf extracts of three edible African nightshade species, Solanum
      sarrachoides, S. scabrum and S. villosum, on adult T. evansi females. RESULTS:
      Only the bioactivity of the leaf extract of S. sarrachoides (LC50 7.44 mg mL(-1))
      and that of its most polar fraction (LC50 5.44 mg mL(-1)) paralleled that of the
      positive control, neem oil (LC50 1.89 mg mL(-1)), across all doses tested. Liquid
      chromatography-quadruple time of flight-mass spectrometry identified a mixture of
      steroidal glycoalkaloids (SGAs), including alpha-solasonine, alpha-solamargine
      and derivatives of tomatine and demissine, which were neither detected in the
      crude extract nor in any of the fractions obtained from S. scabrum and S.
      villosum. CONCLUSION: Our results suggest that the presence of SGAs may play a
      key role in the differential defence of edible African nightshades against attack
      by T. evansi. These findings may add to the plethora of environmentally friendly
      tools from natural plant products for management of T. evansi.

PMID- 26299256
TI  - Ultrasonography of the optic nerve sheath to assess intracranial pressure changes
      after ventriculo-peritoneal shunt surgery in children with hydrocephalus: a
      prospective observational study.
AB  - The optic nerve sheath diameter has been verified by various clinical studies as
      a non-invasive indicator of intracranial hypertension. The aim of this study was
      to compare the optic nerve sheath diameter before and immediately after
      ventriculo-peritoneal shunt surgery in children with hydrocephalus. We analysed
      transorbital ultrasonographic images recorded after induction of anaesthesia and
      30 min after shunt insertion in 34 children, measuring the optic nerve sheath
      diameters using a linear ultrasound probe. The mean (SD) optic nerve sheath
      diameters were 5.4 (0.6) mm (right) and 5.3 (0.7) mm (left) before surgery and
      4.4 (0.5) mm (right) and 4.5 (0.7) mm (left) after surgery (p < 0.0001 for before
      and after comparisons for both eyes). The technique allows rapid and non-invasive
      assessment of intracranial pressure to guide appropriate postoperative
      management.

PMID- 26299257
TI  - Mammalian target of rapamycin, insulin resistance and hidradenitis suppurativa: a
      possible metabolic loop.

PMID- 26299258
TI  - Lack of Impact of High Dietary Vitamin A on T Helper 2-Dependent Contact
      Hypersensitivity to Fluorescein Isothiocyanate in Mice.
AB  - Overuse of vitamin A as a dietary supplement is a concern in industrialized
      countries. High-level dietary vitamin A is thought to shift immunity to a T
      helper 2 (Th2)-dominant one, resulting in the promotion of allergies. We have
      been studying a fluorescein isothiocyanate (FITC)-induced contact
      hypersensitivity (CHS) mouse model that involves Th2-type immunity. We fed a diet
      with a high retinyl palmitate content (250 international units (IU)/g diet) or a
      control diet (4 IU/g diet) to BALB/c mice for three weeks. No augmentation of
      FITC-induced CHS was found in mice fed the diet with a high vitamin A content,
      although accumulation of the vitamin was confirmed in the livers of these
      animals. The results indicated that relatively short-term feeding of the high
      level vitamin A diet did not influence the Th2-driven response at a stage with
      significant retinol accumulation in the liver. The results were in contrast to
      the high-dose pyridoxine diets that produced a reduced response in FITC-induced
      CHS. 

PMID- 26299259
TI  - Sample collection and amino acids analysis of extracellular fluid of mouse brain
      slices with low flow push-pull perfusion.
AB  - Brain tissue slices are a common neuroscience model that allows relatively
      sophisticated analysis of neuronal networks in a simplified preparation. Most
      experimental methodology utilizes electrophysiological tools to probe these model
      systems. The work here demonstrates the adaptation of low-flow push-pull
      perfusion sampling (LFPS) to a brain slice system. LFPS is used to sample from
      the hippocampus of mouse brain slices. Perfusate amino acid levels are quantified
      following sampling with capillary electrophoresis. Glutamate was measured from
      the CA1 region of the hippocampus in slices taken from a cystine-glutamate
      transporter deletion mutant, xCT(-/-), and the background strain C57BL/6J.
      Sampling is performed over up to 6.5 h with standard tissue slice preparation and
      experimentation methods. Four amino acids were quantified to demonstrate the
      ability to perform LFPS and show good agreement with published literature.
      Perfusate glutamate levels are found to be significantly lower with xCT(-/-)
      slices (1.9(+/-0.5) MUM) relative to controls (4.90(+/-1.1) MUM). But,
      experiments with control slices show a significant decrease in glutamate over the
      6 h sampling period that are not seen with xCT(-/-) slices. Increasing the LFPS
      sample collection rate during the first 90 min of sampling did not show a
      sampling artifact in perfusate glutamate content. Sampling immediately following
      slicing did not show an early increasing glutamate level that would be indicative
      of a significant contribution from blood or tissue damage. The data presented
      here show a complementarity to electrophysiological studies of tissue slices. The
      ability to characterize extracellular fluid chemical content with LFPS in these
      slices provides an alternative data stream for probing neurochemical signaling
      networks in brain tissue slices. 

PMID- 26299260
TI  - Effect of 2, 4-di-tert-butylphenol on growth and biofilm formation by an
      opportunistic fungus Candida albicans.
AB  - Candida albicans, an opportunistic pathogen, has been known to form hypoxic
      biofilms on medical devices which in turn confers resistance towards antifungals,
      resulting in subsequent therapeutic failures. Inclusion of anti-biofilm agents in
      the control of infections is a topic of current interest in developing potential
      anti-infectives. The in vitro anti-fungal and anti-biofilm efficacy of 2,4-di
      tert-butyl phenol [DTBP] was evaluated in this study, which revealed the
      potential fungicidal action of DTBP at higher concentrations where fluconazole
      failed to act completely. DTBP also inhibited the production of hemolysins,
      phospholipases and secreted aspartyl proteinase which are the crucial virulence
      factors required for the invasion of C. albicans. Various anti-biofilm assays and
      morphological observations revealed the efficacy of DTBP in both inhibiting and
      disrupting biofilms of C. albicans. Inhibition of hyphal development, a key
      process that aids in initial adhesion of C. albicans, was observed, and this
      could be a mechanism for the anti-biofilm activity of DTBP.

PMID- 26299261
TI  - Differences in health-related quality of life and caregiver burden after hip and
      spine surgery in non-ambulatory children with severe cerebral palsy.
AB  - AIM: The aim of this study was to evaluate changes in caregivers' perceptions of
      health-related quality of life (HRQOL) and caregiver impact in children with
      severe, non-ambulatory cerebral palsy after orthopedic surgery to correct hip or
      spine deformities. METHOD: A prospective longitudinal cohort study (n=44) design
      was used to measure changes before and after surgery. Caregivers completed the
      Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD)
      and the Assessment of Caregiver Experience with Neuromuscular Disease (ACEND).
      Data collection was between February 2011 and February 2014. Caregivers were
      included if their child was 3 to 25 years old, had cerebral palsy in Gross Motor
      Function Classification System levels IV and V, and was scheduled for orthopedic
      surgery. Analysis of variance with repeated measures was used to assess changes
      before and at four time points after surgery. RESULTS: Forty-four caregivers
      participated. Caregivers' perceptions of their child's HRQOL demonstrated an
      improvement from baseline to 12 months (p<0.001). Patients who had spine surgery
      demonstrated a steady improvement over time, whereas patients who had hip surgery
      had a decrease at 6 weeks followed by steady improvement. Improvements were noted
      in five of six of the CPCHILD domains, with no changes in the quality of life
      domain. No changes were noted in any of the ACEND domains. INTERPRETATION:
      Caregivers report an improvement in a variety of domains of HRQOL 1 year after
      orthopedic surgery.

PMID- 26299262
TI  - Performance of PCR-REBA assay for screening and identifying pathogens directly in
      whole blood of patients with suspected sepsis.
AB  - AIMS: Rapid and accurate identification of a broad range of bacterial and fungal
      pathogens is the key to successful management of patients with bloodstream
      infections (BSIs). The aim of this study was to evaluate the diagnostic
      performance of PCR-REBA Sepsis-ID test for the detection of BSIs pathogens.
      METHODS AND RESULTS: EDTA anticoagulated blood for REBA Sepsis-ID assay and blood
      culture samples from 882 patients with suspected sepsis were simultaneously
      collected from January 2014 to December 2014. Of 115 patients with positive blood
      culture, 64 (55.7%) were Gram-positive bacteria, 35 (30.4%) were Gram-negative
      bacteria, 1 (0.9%) was Candida albicans and 15 (13.0%) were polymicrobial
      infections. The concordance rate of blood culture system and PCR-REBA Sepsis ID
      test was 83.0% (95% confidence interval (CI), 79.8-84.8, P < 0.0001). Compared to
      blood culture, the diagnosis of bacterial proven pathogens by PCR-REBA revealed
      81.0% (95% CI, 73.4-86.8, P < 0.0001) sensitivity, 83.4% (95% CI, 80.0-85.4, P <
      0.0001) specificity, 80.9% positive and 95.8% negative predictive values
      respectively. In 10 cases with PCR-REBA positive but blood culture negative, the
      levels of C-reactive protein were significantly elevated 18.5 mg dl(-1) (SD +/-
      13.7, 95% CI 1.8-41.9) and six cases has been proven to have pathogen by
      bacterial 16S rRNA sequencing. Although the sensitivity for pathogen
      identification was not significantly different between PCR-REBA and blood culture
      (P = 0.5), the combination of the two methods resulted in a significantly
      increased rate of pathogen detection (P = 0.002). The results of this study
      suggested that PCR-REBA may be helpful when added to blood culture in the
      diagnosis and management of sepsis. CONCLUSIONS: PCR-REBA Sepsis-ID test is a
      useful tool for the rapid identification of pathogenic isolates in whole blood to
      ensure adequate treatment for the causative agents of BSIs. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Although the cost of molecular diagnostic assays is higher
      than the cost of conventional methods, clinical and economic cost-benefit
      analysis is still needed. PCR-REBA may provide essential information for
      accelerating therapeutic decisions to ensure effective treatment with antibiotics
      in the acute phase of pathogen infection.

PMID- 26299263
TI  - The Role of Bone Morphogenetic Proteins 2, 7, and 14 in Approaches for
      Intervertebral Disk Restoration.

PMID- 26299264
TI  - Health Burden of Adult Spinal Deformity Compared with Other Chronic Diseases.

PMID- 26299265
TI  - Futuristic Three-Dimensional Printing and Personalized Neurosurgery.

PMID- 26299266
TI  - Vascular Specification, Wnts, and Central Nervous System Lymphatics.

PMID- 26299267
TI  - Network analysis of host-virus communities in bats and rodents reveals
      determinants of cross-species transmission.
AB  - Bats are natural reservoirs of several important emerging viruses. Cross-species
      transmission appears to be quite common among bats, which may contribute to their
      unique reservoir potential. Therefore, understanding the importance of bats as
      reservoirs requires examining them in a community context rather than
      concentrating on individual species. Here, we use a network approach to identify
      ecological and biological correlates of cross-species virus transmission in bats
      and rodents, another important host group. We show that given our current
      knowledge the bat viral sharing network is more connected than the rodent
      network, suggesting viruses may pass more easily between bat species. We identify
      host traits associated with important reservoir species: gregarious bats are more
      likely to share more viruses and bats which migrate regionally are important for
      spreading viruses through the network. We identify multiple communities of viral
      sharing within bats and rodents and highlight potential species traits that can
      help guide studies of novel pathogen emergence.

PMID- 26299269
TI  - Synthesis, Characterization, and Stoichiometric U-O Bond Scission in Uranyl
      Species Supported by Pyridine(diimine) Ligand Radicals.
AB  - Two uranium(VI) uranyl compounds, Cp*UO2((Mes)PDI(Me)) (3) and Cp*UO2((t)Bu
      (Mes)PDI(Me)) (3-(t)Bu) (Cp* = 1,2,3,4,5-pentamethylcyclopentadienide;
      (Mes)PDI(Me) = 2,6-((Mes)N=CMe)2C5H3N; (t)Bu-(Mes)PDI(Me) = 2,6-((Mes)N=CMe)2-p
      C(CH3)3C5H2N; Mes = 2,4,6-trimethylphenyl), have been synthesized by addition of
      N-methylmorpholine N-oxide to trianionic pyridine(diimine) uranium(IV)
      precursors, Cp*U((Mes)PDI(Me))(THF) (1), Cp*U((Mes)PDI(Me))(HMPA) (1-HMPA), and
      Cp*U((t)Bu-(Mes)PDI(Me))(THF) (1-(t)Bu). These uranyl complexes contain singly
      reduced pyridine(diimine) ligands suggesting formation occurs via cooperative
      ligand/metal oxidation. Treating 3 or 3-(t)Bu with stoichiometric equivalents of
      Me3SiI results in stepwise oxo silylation to form (Me3SiO)2UI2((Mes)PDI(Me)) (5)
      or (Me3SiO)UI2((t)Bu-(Mes)PDI(Me)) (5-(t)Bu), respectively. Additional
      equivalents result in full uranium-oxo bond scission and formation of UI4(1,4
      dioxane)2 with extrusion of hexamethyldisiloxane. The uranium complexes have been
      characterized via multinuclear NMR, vibrational, and electronic absorption
      spectroscopies and, in some cases, X-ray crystallography. 

PMID- 26299268
TI  - DOT1L Activity Promotes Proliferation and Protects Cortical Neural Stem Cells
      from Activation of ATF4-DDIT3-Mediated ER Stress In Vitro.
AB  - Growing evidence suggests that the lysine methyltransferase DOT1L/KMT4 has
      important roles in proliferation, survival, and differentiation of stem cells in
      development and in disease. We investigated the function of DOT1L in neural stem
      cells (NSCs) of the cerebral cortex. The pharmacological inhibition and shRNA
      mediated knockdown of DOT1L impaired proliferation and survival of NSCs. DOT1L
      inhibition specifically induced genes that are activated during the unfolded
      protein response (UPR) in the endoplasmic reticulum (ER). Chromatin
      immunoprecipitation analyses revealed that two genes encoding for central
      molecules involved in the ER stress response, Atf4 and Ddit3 (Chop), are marked
      with H3K79 methylation. Interference with DOT1L activity resulted in
      transcriptional activation of both genes accompanied by decreased levels of H3K79
      dimethylation. Although downstream effectors of the UPR, such as Ppp1r15a/Gadd34,
      Atf3, and Tnfrsf10b/Dr5 were also transcriptionally activated, this most likely
      occurred in response to increased ATF4 expression rather than as a direct
      consequence of altered H3K79 methylation. While stem cells are particularly
      vulnerable to stress, the UPR and ER stress have not been extensively studied in
      these cells yet. Since activation of the ER stress program is also implicated in
      directing stem cells into differentiation or to maintain a proliferative status,
      the UPR must be tightly regulated. Our and published data suggest that histone
      modifications, including H3K4me3, H3K14ac, and H3K79me2, are implicated in the
      control of transcriptional activation of ER stress genes. In this context, the
      loss of H3K79me2 at the Atf4- and Ddit3-promoters appears to mark a point-of-no
      return that activates the death program in NSCs.

PMID- 26299271
TI  - Phenotypic plasticity is not affected by experimental evolution in constant,
      predictable or unpredictable fluctuating thermal environments.
AB  - The selective past of populations is presumed to affect the levels of phenotypic
      plasticity. Experimental evolution at constant temperatures is generally expected
      to lead to a decreased level of plasticity due to presumed costs associated with
      phenotypic plasticity when not needed. In this study, we investigated the effect
      of experimental evolution in constant, predictable and unpredictable daily
      fluctuating temperature regimes on the levels of phenotype plasticity in several
      life history and stress resistance traits in Drosophila simulans. Contrary to the
      expectation, evolution in the different regimes did not affect the levels of
      plasticity in any of the traits investigated even though the populations from the
      different thermal regimes had evolved different stress resistance and fitness
      trait means. Although costs associated with phenotypic plasticity are known, our
      results suggest that the maintenance of phenotypic plasticity might come at low
      and negligible costs, and thus, the potential of phenotypic plasticity to evolve
      in populations exposed to different environmental conditions might be limited. 

PMID- 26299272
TI  - Using an evidence-based care bundle to improve initial emergency nursing
      management of patients with severe traumatic brain injury.
AB  - AIMS AND OBJECTIVES: To test the feasibility of an evidence-based care bundle in
      a Thai emergency department. The specific objective of this study was to examine
      the impact of the implementation of the care bundle on the initial emergency
      nursing management of patients with severe traumatic brain injury. BACKGROUND: A
      care bundle approach is one strategy used to improve the consistency, quality and
      safety of emergency care for different patients groups, however, has not been
      tested in patients with severe traumatic brain injury. DESIGN: A pretest/post
      test design was used. The study intervention was an evidence-based care bundle
      for initial emergency nursing management of patients with severe traumatic brain
      injury. METHODS: Nonparticipant observations were conducted between October 2012
      June 2013 at an emergency department of a 640 bed regional hospital in Southern
      Thailand. The initial emergency nursing care was observed in 45 patients with
      severe traumatic brain injury: 20 patients in the pretest period and 25 patients
      in the post-test period. RESULTS: There were significant improvements in clinical
      care of patients with severe traumatic brain injury after implementation of the
      care bundle: (1) use of end-tidal carbon dioxide monitoring, (2) frequency of
      respiratory rate assessment, (3) frequency of pulse rate and blood pressure
      assessment, and (4) patient positioning. CONCLUSION: This study demonstrated that
      implementation of an evidence-based care bundle improved specific elements of
      emergency nurses' clinical management of patients with severe traumatic brain
      injury. RELEVANCE TO CLINICAL PRACTICE: The study suggests that a care bundle
      approach can be used as a strategy to improve emergency nursing care of patients
      with severe traumatic brain injury.

PMID- 26299270
TI  - Cardiopulmonary and arterial baroreceptor unloading during passive hyperthermia
      does not contribute to hyperthermia-induced hyperventilation.
AB  - NEW FINDINGS: What is the central question of this study? Does baroreceptor
      unloading during passive hyperthermia contribute to increases in ventilation and
      decreases in end-tidal carbon dioxide during that exposure? What is the main
      finding and its importance? Hyperthermic hyperventilation is not mitigated by
      expanding central blood volume and reloading the cardiopulmonary baroreceptors
      via rapid saline infusion or by reloading the arterial baroreceptors via
      phenylephrine administration. The absence of a reduction in ventilation upon
      reloading the baroreceptors to pre-hyperthermic levels indicates that
      cardiopulmonary and arterial baroreceptor unloading with hyperthermia is unlikely
      to contribute to hyperthermic hyperventilation in humans. This study tested the
      hypothesis that baroreceptor unloading during passive hyperthermia contributes to
      increases in ventilation and decreases in end-tidal partial pressure of carbon
      dioxide (P ET ,CO2) during that exposure. Two protocols were performed, in which
      healthy subjects underwent passive hyperthermia (increasing intestinal
      temperature by ~1.8 degrees C) to cause a sustained increase in ventilation and
      reduction in P ET ,CO2. Upon attaining hyperthermic hyperventilation, in protocol
      1 (n = 10; three females) a bolus (19 +/- 2 ml kg(-1) ) of warm (~38 degrees C)
      isotonic saline was rapidly (5-10 min) infused intravenously to restore
      reductions in central venous pressure, whereas in protocol 2 (n = 11; five
      females) phenylephrine was infused intravenously (60-120 MUg min(-1) ) to return
      mean arterial pressure to normothermic levels. In protocol 1, hyperthermia
      increased ventilation (by 2.2 +/- 1.7 l min(-1) , P < 0.01), while reducing P ET
      ,CO2 (by 4 +/- 3 mmHg, P = 0.04) and central venous pressure (by 5 +/- 1 mmHg, P
      <0.01). Saline infusion increased central venous pressure by 5 +/- 1 mmHg (P <
      0.01), restoring it to normothermic values, but did not change ventilation or P
      ET ,CO2 (P > 0.05). In protocol 2, hyperthermia increased ventilation (by 5.0 +/-
      2.7 l min(-1) , P <0.01) and reduced P ET ,CO2 (by 5 +/- 2 mmHg, P < 0.01) and
      mean arterial pressure (by 9 +/- 7 mmHg, P <0.01). Phenylephrine infusion
      increased mean arterial pressure by 12 +/- 3 mmHg (P < 0.01), restoring it to
      normothermic values, but did not change ventilation or P ET ,CO2 (P > 0.05). The
      absence of a reduction in ventilation upon reloading the cardiopulmonary and
      arterial baroreceptors to pre-hyperthermic levels indicates that baroreceptor
      unloading with hyperthermia is unlikely to contribute to hyperthermic
      hyperventilation in humans.

PMID- 26299273
TI  - Marijuana Use in Epilepsy: The Myth and the Reality.
AB  - Marijuana has been utilized as a medicinal plant to treat a variety of conditions
      for nearly five millennia. Over the past few years, there has been an
      unprecedented interest in using cannabis extracts to treat epilepsy, spurred on
      by a few refractory pediatric cases featured in the media that had an almost
      miraculous response to cannabidiol-enriched marijuana extracts. This review
      attempts to answer the most important questions a clinician may have regarding
      the use of marijuana in epilepsy. First, we review the preclinical and human
      evidences for the anticonvulsant properties of the different cannabinoids, mainly
      tetrahydrocannabinol (THC) and cannabidiol (CBD). Then, we explore the safety
      data from animal and human studies. Lastly, we attempt to reconcile the
      controversy regarding physicians' and patients' opinions about whether the
      available evidence is sufficient to recommend the use of marijuana to treat
      epilepsy. 

PMID- 26299274
TI  - Treatment of Super-Refractory Status Epilepticus.
AB  - Super-refractory status epilepticus (SRSE) is a devastating neurological
      condition with limited treatment options. We conducted an extensive literature
      search to identify and summarize the therapeutic options for SRSE. The search
      mainly resulted in case reports of various pharmacologic and non-pharmacologic
      treatments. The success rate of each of the following agents, ketamine, inhaled
      anesthetics, intravenous immunoglobulin G (IVIG), IV steroids, ketogenic diet,
      hypothermia, electroconvulsive therapy (ECT), transcranial magnetic stimulation
      (TMS), and vagal nerve stimulation (VNS), are discussed in greater detail. The
      choice of appropriate treatment options for a given patient is based on clinical
      presentation. This review focuses on evidence-based, pharmacotherapeutic
      strategies for patients in SRSE. 

PMID- 26299275
TI  - Update on TBI and Cognitive Impairment in Military Veterans.
AB  - Traumatic brain injury (TBI) is a common cause of morbidity and mortality in
      military life. Interest in military TBI has increased recently due to the
      conflicts in Iraq and Afghanistan. Certain types of TBI are relatively unique to
      the military, the most prominent being blast-related TBI. Blast-related mild TBI
      has been of particular concern in veterans from the most recent conflicts
      although controversy remains concerning its separation from post-traumatic stress
      disorder. TBI is also a risk factor for the later development of
      neurodegenerative diseases in which cognitive impairment is prominent putting
      veterans at risk for disorders including Alzheimer's disease and chronic
      traumatic encephalopathy. Recent evidence associating TBI with chronic cognitive
      impairment is reviewed in the context of its relevance to military veterans. 

PMID- 26299276
TI  - Update on Hippocampal Sclerosis.
AB  - The diagnostic hallmarks of hippocampal sclerosis (HS) are severe volume loss of
      the hippocampus, severe neuronal loss, and reactive gliosis involving primarily
      two especially vulnerable fields, CA1 and the subiculum. Occasionally, HS may be
      the only neuropathological change detected in older individuals with dementia and
      is known as pure HS. In the majority of cases, HS occurs in the setting of other
      degenerative changes, usually Alzheimer's disease (AD). In these cases, it is
      classified as combined HS. Although a clinical profile for HS has been
      identified, its similarities with AD make the diagnosis during life quite
      challenging; thus, the diagnosis is often made postmortem. The pathogenesis of HS
      is not completely understood, but the strong association with transactive
      response DNA-binding protein 43 (TDP-43), in approximately 90%, and the recent
      discovery of genetic risk factors are important contributions to a better
      understanding of the disease process.

PMID- 26299278
TI  - Spanish Adaptation and Validation of the Posttraumatic Growth Inventory-Short
      Form.
AB  - The purpose of this article is to adapt and validate the short form of the
      Posttraumatic Growth Inventory (PTGI-SF) in Spanish. The scale consists of 10
      items distributed in 5 posttraumatic growth dimensions measured in the original
      instrument. The psychometric properties and dimensionality of the scale are
      examined in a sample of college students (N = 681). Results lend support to the
      validity and reliability (alpha = .83) of the PTGI-SF. The dimensions of PTGI-SF
      show correlations ranging between .29 and .52. In addition, the inventory
      correlates significantly with deliberate rumination (r = .39) and the search for
      meaning in life (r = .32). The factor loadings of the items in the confirmatory
      factor analysis varied between .52 and .87, showing good fit indexes (comparative
      fit index = .97, Tucker-Lewis index = .93, relative fit index = .90, incremental
      fit index = .97, normed fit index = .96, and root mean square error of
      approximation = .05). Multi-group confirmatory factor analysis supported
      invariance of the PTGI-SF across the 2 groups. Finally, significantly higher PTGI
      SF scores were observed in subjects who were actively looking for meaning in
      life, or had found it after a seeking process, than in subjects who had not
      looked for meaning in life or had given up because they had not been successful.

PMID- 26299277
TI  - Lymphoid susceptibility to the Aggregatibacter actinomycetemcomitans cytolethal
      distending toxin is dependent upon baseline levels of the signaling lipid,
      phosphatidylinositol-3,4,5-triphosphate.
AB  - The Aggregatibacter actinomycetemcomitans cytolethal distending toxin (Cdt)
      induces G2 arrest and apoptosis in lymphocytes and other cell types. We have
      shown that the active subunit, CdtB, exhibits phosphatidylinositol-3,4,5
      triphosphate (PIP3) phosphatase activity and depletes lymphoid cells of PIP3.
      Hence we propose that Cdt toxicity results from depletion of this signaling lipid
      and perturbation of phosphatidylinositol-3-kinase (PI-3K)/PIP3/Akt signaling. We
      have now focused on the relationship between cell susceptibility to CdtB and
      differences in the status of baseline PIP3 levels. Our studies demonstrate that
      the baseline level of PIP3, and likely the dependence of cells on steady-state
      activity of the PI-3K signaling pathway for growth and survival, influence cell
      susceptibility to the toxic effects of Cdt. Jurkat cells with known defects in
      both PIP3 degradative enzymes, PTEN and SHIP1, not only contain high baseline
      levels of PIP3, pAkt, and pGSK3beta, but also exhibit high sensitivity to Cdt. In
      contrast, HUT78 cells, with no known defects in this pathway, contain low levels
      of PIP3, pAkt, and pGSK3beta and likely minimal dependence on the PI-3K signaling
      pathway for growth and survival, and exhibit reduced susceptibility to Cdt. These
      differences in susceptibility to Cdt cannot be explained by differential toxin
      binding or internalization of the active subunit. Indeed, we now demonstrate that
      Jurkat and HUT78 cells bind toxin at comparable levels and internalize relatively
      equal amounts of CdtB. The relevance of these observations to the mode of action
      of Cdt and its potential role as a virulence factor is discussed.

PMID- 26299279
TI  - Environmental stress speeds up DNA replication in Pseudomonas putida in chemostat
      cultivations.
AB  - Cellular response to different types of stress is the hallmark of the cell's
      strategy for survival. How organisms adjust their cell cycle dynamics to
      compensate for changes in environmental conditions is an important unanswered
      question in bacterial physiology. A cell using binary fission for reproduction
      passes through three stages during its cell cycle: a stage from cell birth to
      initiation of replication, a DNA replication phase and a period of cell division.
      We present a detailed analysis of durations of cell cycle phases, investigating
      their dynamics under environmental stress conditions. Applying continuous steady
      state cultivations (chemostats), the DNA content of a Pseudomonas putida KT2440
      population was quantified with flow cytometry at distinct growth rates. Data
      driven modeling revealed that under stress conditions, such as oxygen
      deprivation, solvent exposure and decreased iron availability, DNA replication
      was accelerated correlated to the severity of the imposed stress (up to 1.9
      fold). Cells maintained constant growth rates by balancing the shortened
      replication phase with extended cell cycle phases before and after replication.
      Transcriptome data underpin the transcriptional upregulation of crucial genes of
      the replication machinery. Hence adaption of DNA replication speed appears to be
      an important strategy to withstand environmental stress. 

PMID- 26299280
TI  - Enhanced immunogenicity of multivalent MUC1 glycopeptide antitumour vaccines
      based on hyperbranched polymers.
AB  - Enhancing the immunogenicity of an antitumour vaccine still poses a major
      challenge. It depends upon the selected antigen and the mode of its presentation.
      We here describe a fully synthetic antitumour vaccine, which addresses both
      aspects. For the antigen, a tumour-associated MUC1 glycopeptide as B-cell epitope
      was synthesised and linked to the immunostimulating T-cell epitope P2 derived
      from tetanus toxoid. The MUC1-P2 conjugate is presented multivalently on a
      hyperbranched polyglycerol to the immune system. In comparison to a related
      vaccine of lower multivalency, this vaccine exposing more antigen structures on
      the hyperbranched polymer induced significantly stronger immune responses in mice
      and elicited IgG antibodies of distinctly higher affinity to epithelial tumour
      cells. 

PMID- 26299282
TI  - Gas Transport Resistance in Polymer Electrolyte Thin Films on Oxygen Reduction
      Reaction Catalysts.
AB  - Significant reductions in expensive platinum catalyst loading for the oxygen
      reduction reaction are needed for commercially viable fuel cell electric vehicles
      as well as other important applications. In reducing loading, a resistance at the
      Pt surface in the presence of thin perfluorosulfonic acid (PFSA) electrolyte
      film, on the order of 10 nm thick, becomes a significant barrier to adequate
      performance. However, the resistance mechanism is unresolved and could be due to
      gas dissolution kinetics, increased diffusion resistance in thin films, or
      electrolyte anion interactions. A common hypothesis for the origin of the
      resistance is a highly reduced oxygen permeability in the thin polymer
      electrolyte films that coat the catalyst relative to bulk permeability that is
      caused by nanoscale confinement effects. Unfortunately, the prior work has not
      separated the thin-film gas transport resistance from that associated with PFSA
      interactions with a polarized catalyst surface. Here, we present the first
      characterization of the thin-film O2 transport resistance in the absence of a
      polarized catalyst, using a nanoporous substrate that geometrically mimics the
      active catalyst particles. Through a parametric study of varying PFSA film
      thickness, as thin as 50 nm, we observe no enhanced gas transport resistance in
      thin films as a result of either interfacial effects or structural changes in the
      PFSA. Our results suggest that other effects, such as anion poisoning at the Pt
      catalyst, could be the source of the additional resistance observed at low Pt
      loading. 

PMID- 26299281
TI  - Hydrogen sulfide attenuates doxorubicin-induced cardiotoxicity by inhibiting
      reactive oxygen species-activated extracellular signal-regulated kinase 1/2 in
      H9c2 cardiac myocytes.
AB  - Doxorubicin (DOX) is a potent and available antitumor therapeutic agent; however,
      its clinical application is limited due to its cardiotoxicity. Preliminary
      evidence suggests that hydrogen sulfide (H2S) may exert protective effects on DOX
      induced cardiotoxicity. Therefore, the aim of the present study was to
      investigate whether the extracellular signal-regulated kinase (ERK) 1/2 signaling
      pathway is involved in the cardioprotection of H2S against DOX-induced
      cardiotoxicity. The present study demonstrated that pretreatment with sodium
      hydrosulfide (NaHS; a donor of H2S) prior to DOX exposure attenuated the
      decreased cell viability, the increased apoptosis rate and the intracellular
      accumulation of reactive oxygen species (ROS) in H9c2 cardiac myocytes. Exposure
      of H9c2 cardiac myocytes to DOX upregulated the expression levels of
      phosphorylated ERK1/2, which had been reduced by pretreatment with NaHS or N
      acetyl-L-cysteine, a ROS scavenger. In addition, H2S upregulated the anti
      apoptotic protein, Bcl-2 and downregulated the pro-apoptotic protein, Bax.
      Notably, U0126, a selective inhibitor of ERK1/2, was observed to mimic the above
      mentioned cytoprotective activity of H2S. In conclusion, these findings indicate
      that H2S attenuates DOX-induced cardiotoxicity by inhibiting ROS-mediated
      activation of ERK1/2 in H9c2 cardiac myocytes.

PMID- 26299283
TI  - Elderly and octogenarian cohort: Comparable outcomes with nonelderly cohort after
      open or laparoscopic inguinal hernia repairs.
AB  - PURPOSE: To understand whether the elderly (>65 years of age) or octogenarian
      cohort is at greater risk for poor clinical outcomes after open or laparoscopic
      inguinal hernia repairs. METHODS: Beginning in June 2009, all patients presenting
      to our institution for inguinal hernia repair were asked to participate in a
      prospective database. Demographics, presenting symptoms, preoperative findings on
      examination, intraoperative variables, postoperative outcomes, and readmission
      data were collected. Additionally, patient-centered outcomes were evaluated with
      the Short Form-36 and Carolina Comfort Score questionnaires at follow-up visits
      (3 weeks, 6 months, 1 year, and for the Short Form-36 preoperatively as well).
      RESULTS: A total of 471 patients were included in the study; 285 were nonelderly,
      155 patients were aged 65-80 years, and 31 patients were older than 80 years of
      age. Of these patients, the percent who underwent laparoscopic repair was 86% for
      the nonelderly, 79% for the elderly, and 41.9% for the octogenarian cohorts (P <
      .001). After laparoscopic repairs, the older cohorts had greater rates of minor
      postoperative complications than the nonelderly cohort (38% and 58% vs 15%; P <
      .001) attributable to greater rates of seroma and urinary retention.
      Intraoperative complications and recurrence rates were not different among the
      cohorts; however, the octogenarian cohort was more likely to be readmitted
      compared with both the nonelderly and elderly cohorts (17% vs 2% and 2%,
      respectively, P < .001) and to have a greater duration of stay (P < .001). For
      laparoscopic repairs over all the cohorts, the Carolina Comfort Scale improved
      over time (P < .001). Laparoscopic repairs in the octogenarians (P = .07) but not
      in the elderly (P = .6) had better scores over time (8.1 and 1.0 and points
      less/better, respectively) than the nonelderly cohort. CONCLUSION: Laparoscopic
      inguinal hernia repair is safe and effective in elderly and octogenarian patients
      with no major morbidities or mortalities. Although these patients are at greater
      risk for postoperative seroma and urinary retention, and octogenarians are at
      greater risk for readmission, patient-centered outcomes may be better after
      laparoscopic repairs with the proper patient selection in the older population.

PMID- 26299285
TI  - Failure of the Platelet Function Assay (PFA)-100 to detect antiplatelet agents.
AB  - BACKGROUND: Antiplatelet therapy is a complicating factor in patients with
      traumatic brain injuries (TBI), as well as those with hemorrhagic cerebrovascular
      accidents (CVAs). Platelet Function Assay (PFA)-100 is a coagulation device that
      can detect platelet dysfunction caused by aspirin and adenosine diphosphate
      inhibition. Our retrospective study reviewed the effectiveness of PFA-100 in
      detecting platelet dysfunction caused by aspirin and clopidogrel and determined
      its clinical importance. METHODS: All patients with PFA-100 tests from January
      2013 to February 2014 were collected. Diagnoses indicative of a TBI or CVA were
      chosen for analysis. Patients with a normal PFA-100 indicating no platelet
      dysfunction but with documented aspirin and/or clopidogrel use were selected. An
      extensive chart review was performed to determine the relevance to their clinical
      care. RESULTS: A total of 475 patients were evaluated with a PFA-100 from January
      2013 to February 2014. PFA-100 detected platelet dysfunction as the result of pre
      injury use of antiplatelet agents in TBI and CVA patients with a sensitivity of
      only 48.6% and a specificity of 74.8%. Had these antiplatelet medications been
      known during initial workup, these patients would have had a change in management
      that may have impacted their outcomes. CONCLUSION: Despite its common usage, the
      PFA-100 is an unreliable tool to assist in the management of TBI and CVA
      patients. Additional investigation into alternative methods for detecting
      platelet dysfunction is warranted.

PMID- 26299287
TI  - Here/In This Issue and There/Abstract Thinking: The Secret Lives of Adolescents:
      Are We Asking the Right Questions?

PMID- 26299288
TI  - Reading Between the Lines: Finding Fundamental Themes in Fiction.

PMID- 26299289
TI  - Genetic Effects, Categorical Disorders, and Quantitative Traits.

PMID- 26299290
TI  - Naturalistic Studies and the Rigor of Psychopharmacology Trials Yet to Come.

PMID- 26299291
TI  - Meta-Assurance: No Tic Exacerbation Caused by Stimulants.

PMID- 26299292
TI  - Web Intervention for Adolescents Affected by Disaster: Population-Based
      Randomized Controlled Trial.
AB  - OBJECTIVE: To assess the efficacy of Bounce Back Now (BBN), a modular, Web-based
      intervention for disaster-affected adolescents and their parents. METHOD: A
      population-based randomized controlled trial used address-based sampling to
      enroll 2,000 adolescents and parents from communities affected by tornadoes in
      Joplin, MO, and several areas in Alabama. Data collection via baseline and follow
      up semi-structured telephone interviews was completed between September 2011 and
      August 2013. All families were invited to access the BBN study Web portal
      irrespective of mental health status at baseline. Families who accessed the Web
      portal were assigned randomly to 1 of 3 groups: BBN, which featured modules for
      adolescents and parents targeting adolescents' mental health symptoms; BBN plus
      additional modules targeting parents' mental health symptoms; or assessment only.
      The primary outcomes were adolescent symptoms of posttraumatic stress disorder
      (PTSD) and depression. RESULTS: Nearly 50% of families accessed the Web portal.
      Intent-to-treat analyses revealed time * condition interactions for PTSD symptoms
      (B = -0.24, SE = 0.08, p < .01) and depressive symptoms (B = -0.23, SE = 0.09, p
      < .01). Post hoc comparisons revealed fewer PTSD and depressive symptoms for
      adolescents in the experimental versus control conditions at 12-month follow-up
      (PTSD: B = -0.36, SE = 0.19, p = .06; depressive symptoms: B = -0.42, SE = 0.19,
      p = 0.03). A time * condition interaction also was found that favored the BBN
      versus BBN + parent self-help condition for PTSD symptoms (B = 0.30, SE = 0.12, p
      = .02) but not depressive symptoms (B = 0.12, SE = 0.12, p = .33). CONCLUSION:
      Results supported the feasibility and initial efficacy of BBN as a scalable
      disaster mental health intervention for adolescents. Technology-based solutions
      have tremendous potential value if found to reduce the mental health burden of
      disasters. CLINICAL TRIAL REGISTRATION INFORMATION: Web-based Intervention for
      Disaster-Affected Youth and Families; http://clinicaltrials.gov; NCT01606514.

PMID- 26299293
TI  - Neuromotor Adverse Effects in 342 Youth During 12 Weeks of Naturalistic Treatment
      With 5 Second-Generation Antipsychotics.
AB  - OBJECTIVE: Second-generation antipsychotic (SGA) effects in youth were monitored
      to quantify extrapyramidal side effects (EPS) and to identify risk profiles for
      treatment-emergent EPS. METHOD: Data were analyzed for the nonrandomized,
      prospective Second-generation Antipsychotic Treatment Indications, Effectiveness
      and Tolerability in Youth (SATIETY) inception cohort study. EPS were assessed at
      baseline and 4, 8, and 12 weeks after naturalistic SGA initiation for
      schizophrenia, mood, disruptive behavior, and autism spectrum disorders using the
      Simpson-Angus Scale (SAS), Barnes Akathisia Scale, Abnormal Involuntary Movement
      Scale (AIMS), and Treatment Emergent Side Effect Scale. Drug-induced parkinsonism
      was defined by incident mean SAS score >0.33, anticholinergic initiation, or
      increasing total SAS score >=2 in patients with baseline EPS. RESULTS: In 342
      youth aged 13.6 +/- 3.5 years (male = 58.2%, antipsychotic-naive = 65.8%), 15.2%
      developed drug-induced parkinsonism. Raw SGA-grouped drug-induced parkinsonism
      rates were as follows: quetiapine = 1.5%, olanzapine = 13.8%, risperidone =
      16.1%, ziprasidone = 20.0%, and aripiprazole = 27.3%. SGA type, dose, higher age,
      and lower baseline functioning were jointly associated with drug-induced
      parkinsonism (R(2) = 0.18; p < .0001). Controlling for these factors, drug
      induced parkinsonism rates were significantly lower only for quetiapine and
      olanzapine. Subjectively reported EPS (5%), EPS-related treatment discontinuation
      (3.3%), and anticholinergic initiation (3%) were infrequent. Anticholinergic
      initiation was most frequent with risperidone (10.2%; p = .0004). Treatment
      emergent dyskinesia ranged from 4.5% (aripiprazole) to 15.5% (olanzapine). SGA
      type, younger age, white race/ethnicity, and baseline AIMS were jointly
      associated with treatment-emergent dyskinesia (R(2) = 0.31; p < .0001).
      Controlling for these factors, treatment-emergent dyskinesia rates differed among
      SGA subgroups, with higher rates with olanzapine and ziprasidone. At baseline,
      psychostimulant use was associated with dyskinesia, and number of psychotropic
      comedications was associated with subjective EPS. CONCLUSION: In youth, SGA
      related EPS rates did not generally exceed those reported in adults, with
      particularly low rates with quetiapine and olanzapine.

PMID- 26299294
TI  - Meta-Analysis: Risk of Tics Associated With Psychostimulant Use in Randomized,
      Placebo-Controlled Trials.
AB  - OBJECTIVE: Clinical practice currently restricts the use of psychostimulant
      medications in children with tics or a family history of tics for fear that tics
      will develop or worsen as a side effect of treatment. Our goal was to conduct a
      meta-analysis to examine the risk of new onset or worsening of tics as an adverse
      event of psychostimulants in randomized, placebo-controlled trials. METHOD: We
      conducted a PubMed search to identify all double-blind, randomized, placebo
      controlled trials examining the efficacy of psychostimulant medications in the
      treatment of children with attention-deficit/hyperactivity disorder (ADHD). We
      used a fixed effects meta-analysis with risk ratio of new onset or worsening tics
      in children treated with psychostimulants compared to placebo. We used stratified
      subgroup analysis and meta-regression to examine the effects of stimulant type,
      dose, duration of treatment, recorder of side effect data, trial design, and mean
      age of participants on the measured risk of tics. RESULTS: We identified 22
      studies involving 2,385 children with ADHD for inclusion in our meta-analysis.
      New onset tics or worsening of tic symptoms were commonly reported in the
      psychostimulant (event rate = 5.7%, 95% CI = 3.7%-8.6%) and placebo groups (event
      rate = 6.5%, 95% CI = 4.4%-9.5%). The risk of new onset or worsening of tics
      associated with psychostimulant treatment was similar to that observed with
      placebo (risk ratio = 0.99, 95% CI = 0.78-1.27, z = -0.05, p = .962). Type of
      psychostimulant, dose, duration of treatment, recorder, and participant age did
      not affect risk of new onset or worsening of tics. Crossover studies were
      associated with a significantly greater measured risk of tics with
      psychostimulant use compared to parallel group trials. CONCLUSION: Meta-analysis
      of controlled trials does not support an association between new onset or
      worsening of tics and psychostimulant use. Clinicians may want to consider
      rechallenging children who report new onset or worsening of tics with
      psychostimulant use, as these symptoms are much more likely to be coincidental
      rather than caused by psychostimulants.

PMID- 26299295
TI  - Single Nucleotide Polymorphism Heritability of Behavior Problems in Childhood:
      Genome-Wide Complex Trait Analysis.
AB  - OBJECTIVE: Genetic factors contribute to individual differences in behavior
      problems. In children, genome-wide association studies (GWAS) have yielded the
      first suggestive results when aiming to identify genetic variants that explain
      heritability, but the proportion of genetic variance that can be attributed to
      common single nucleotide polymorphisms (SNPs) remains to be determined, as only a
      few studies have estimated SNP heritability, with diverging results. METHOD:
      Genomic-relationship-matrix restricted maximum likelihood (GREML) as implemented
      in the software Genome-Wide Complex Trait Analysis (GCTA) was used to estimate
      SNP heritability (SNP h(2)) for multiple phenotypes within 4 broad domains of
      children's behavioral problems (attention-deficit/hyperactivity symptoms,
      internalizing, externalizing, and pervasive developmental problems) and cognitive
      function. We combined phenotype and genotype data from 2 independent, population
      based Dutch cohorts, yielding a total number of 1,495 to 3,175 of 3-, 7-, and 9
      year-old children. RESULTS: Significant SNP heritability estimates were found for
      attention-deficit/hyperactivity symptoms (SNP h(2) = 0.37-0.71), externalizing
      problems (SNP h(2) = 0.44), and total problems (SNP h(2) = 0.18), rated by mother
      or teacher. Sensitivity analyses with exclusion of extreme cases and quantile
      normalization of the phenotype data decreased SNP h(2) as expected under genetic
      inheritance, but they remained statistically significant for most phenotypes.
      CONCLUSION: We provide evidence of the influence of common SNPs on child behavior
      problems in an ethnically homogenous sample. These results support the
      continuation of large GWAS collaborative efforts to unravel the genetic basis of
      complex child behaviors.

PMID- 26299296
TI  - A Population-Based Imaging Genetics Study of Inattention/Hyperactivity: Basal
      Ganglia and Genetic Pathways.
AB  - OBJECTIVE: Although attention-deficit/hyperactivity disorder (ADHD) is 1 of the
      most common neurodevelopmental disorders, little is known about the neurobiology.
      Clinical studies suggest basal ganglia morphology plays a role. Furthermore,
      hyperactivity/impulsivity symptoms have recently been linked to genetic pathways
      involved in dopamine/norepinephrine and serotonin neurotransmission and neuritic
      outgrowth. We aimed to assess the association between ADHD symptoms, basal
      ganglia volume, and the 3 proposed genetic pathways in a pediatric population
      based sample. With this, we aimed to investigate the generalizability of earlier
      clinical findings to the general population. METHOD: This study included a
      population-based sample of 1,871 children with data on ADHD symptoms and genetic
      data, and 344 children with additional neuroimaging data. Regression analyses
      between ADHD symptom severity and volumetric data of the basal ganglia were
      performed. Also, gene-set analyses investigating the association between both
      ADHD symptom severity and basal ganglia volume with the dopamine/norepinephrine,
      serotonin, and neuritic outgrowth pathways were performed. RESULTS: More
      inattention and hyperactivity/impulsivity symptoms were associated with a smaller
      volume of the putamen (beta = -0.13, p = .034), which was regarded as trend-level
      after correction for multiple testing. Stratified analyses showed a stronger
      putamen-hyperactivity association in children with clinical scores, although a
      similar trend was visible in the nonclinical subsample. The genetic pathways were
      not related to either ADHD symptoms or basal ganglia volume. CONCLUSION: ADHD
      symptoms were marginally related to putamen volume in our population-based
      sample. We found no evidence for a role of dopamine/norepinephrine, serotonin, or
      neuritic outgrowth genetic pathways in ADHD symptom severity.

PMID- 26299297
TI  - Child Maltreatment and Neural Systems Underlying Emotion Regulation.
AB  - OBJECTIVE: The strong associations between child maltreatment and psychopathology
      have generated interest in identifying neurodevelopmental processes that are
      disrupted following maltreatment. Previous research has focused largely on neural
      response to negative facial emotion. We determined whether child maltreatment was
      associated with neural responses during passive viewing of negative and positive
      emotional stimuli and effortful attempts to regulate emotional responses. METHOD:
      A total of 42 adolescents aged 13 to 19 years, half with exposure to physical
      and/or sexual abuse, participated. Blood oxygen level-dependent (BOLD) response
      was measured during passive viewing of negative and positive emotional stimuli
      and attempts to modulate emotional responses using cognitive reappraisal.
      RESULTS: Maltreated adolescents exhibited heightened response in multiple nodes
      of the salience network, including amygdala, putamen, and anterior insula, to
      negative relative to neutral stimuli. During attempts to decrease responses to
      negative stimuli relative to passive viewing, maltreatment was associated with
      greater recruitment of superior frontal gyrus, dorsal anterior cingulate cortex,
      and frontal pole; adolescents with and without maltreatment down-regulated
      amygdala response to a similar degree. No associations were observed between
      maltreatment and neural response to positive emotional stimuli during passive
      viewing or effortful regulation. CONCLUSION: Child maltreatment heightens the
      salience of negative emotional stimuli. Although maltreated adolescents modulate
      amygdala responses to negative cues to a degree similar to that of non-maltreated
      youths, they use regions involved in effortful control to a greater degree to do
      so, potentially because greater effort is required to modulate heightened
      amygdala responses. These findings are promising, given the centrality of
      cognitive restructuring in trauma-focused treatments for children.

PMID- 26299301
TI  - Adsorption of 2-propanol on ice probed by ambient pressure X-ray photoelectron
      spectroscopy.
AB  - The interaction of 2-propanol with ice was examined via ambient pressure X-ray
      photoelectron spectroscopy (APXPS), a surface sensitive technique that probes the
      adsorbed 2-propanol directly with submonolayer resolution. Isothermal uptake
      experiments were performed on vapor deposited ice at 227 K in the presence of the
      equilibrium water vapor pressure of 0.05 Torr and 2-propanol partial pressures
      ranging from 5 * 10(-5) to 2 * 10(-3) Torr. The C 1s APXPS spectra of adsorbed 2
      propanol showed two characteristic peaks associated with the COH alcohol group
      and CMe methyl groups in a 1 : 2 ratio, respectively. Coverage increased with 2
      propanol partial pressure and followed first order Langmuir kinetics with a
      Langmuir constant of K = 6.3 * 10(3) Torr(-1). The 1 : 2 ratio of COH : CMe
      remained constant with increasing coverage, indicating there is no chemical
      reaction upon adsorption. The observed Langmuir kinetics using APXPS is
      consistent with previous observations of other small chain alcohols via indirect
      adsorption methods using, e.g., Knudsen cell and coated wall flow tube reactors. 

PMID- 26299298
TI  - Intrinsic Amygdala Functional Connectivity in Youth With Bipolar I Disorder.
AB  - OBJECTIVE: Bipolar disorder (BD) commonly begins during adolescence and may
      continue into adulthood. Studies in adults with BD suggest that disruptions in
      amygdalar neural circuitry explain the pathophysiology underlying the disorder.
      Importantly, however, amygdala subregion networks have not yet been examined in
      youth close to mania onset. The goal of this study was to compare resting state
      functional connectivity patterns in amygdala subregions in youth with bipolar I
      disorder with patterns in healthy controls. METHOD: Centromedial, laterobasal,
      and superficial amygdala subdivisions were assessed during rest and examined in
      relation to clinical measures of mania in youth (14-20 years old) with bipolar I
      disorder who experienced only a single episode of mania (BD; n = 20) and age
      matched healthy comparison youth without any personal or family history of DSM-IV
      Axis I disorders (HC; n = 23). RESULTS: Relative to HC youth, youth with BD
      exhibited decreased connectivity between the laterobasal subdivision of the
      amygdala and the hippocampus and precentral gyrus, and increased connectivity
      between the laterobasal subdivision and the precuneus. Connectivity between the
      right laterobasal amygdala and right hippocampus was positively correlated with
      levels of anxiety in BD but not in HC youth, and connectivity between the right
      laterobasal amygdala and right precuneus was negatively correlated with insight
      about bipolar illness. CONCLUSION: Youth with BD have abnormal amygdala resting
      state network connections to regions that are critical for emotional processing
      and self-awareness. Longitudinal studies are needed to determine whether these
      aberrant patterns in youth with BD can be altered with intervention and can
      influence the course of disorder.

PMID- 26299299
TI  - Neural Activation During Cognitive Emotion Regulation in Previously Depressed
      Compared to Healthy Children: Evidence of Specific Alterations.
AB  - OBJECTIVE: Impairments in cognitive emotion regulation (CER) have been linked to
      functional neural abnormalities and the pathogenesis of major depressive disorder
      (MDD). Few functional magnetic resonance imaging (fMRI) studies have investigated
      the neural underpinnings of CER in samples with depression. As CER develops in
      childhood, understanding dysfunctional CER-related alterations in brain function
      during this period could advance knowledge of the developmental psychopathology
      of MDD. METHOD: This study tested whether neural activity in brain regions known
      to support cognitive reappraisal differed between healthy 7- to 15-year-old
      children and same-age peers with a history of MDD (MDD-ever). A total of 64
      children participated in this event-related fMRI study, which used a
      developmentally appropriate and validated fMRI reappraisal task. Children were
      instructed to passively view sad or neutral images and to decrease negative
      emotions using cognitive reappraisal. RESULTS: MDD-ever and healthy children
      showed similar patterns of cortical activation during reappraisal, but with a
      significant difference found in 1 key CER region, the left inferior frontal gyrus
      (IFG). In addition, individual differences in CER were associated with left IFG
      activity during reappraisal. CONCLUSION: Alterations in the neurocircuitry of
      reappraisal are evident in children with a depression history compared to healthy
      controls. The finding that MDD-ever children showed reappraisal-related neural
      responses in many regions similar to healthy controls has clinical implications.
      Findings suggest that identification of alterations in reappraisal in children
      with remitted depression, for whom much, although not all, of the neural
      circuitry remains intact, may be an important window of opportunity for
      intervention.

PMID- 26299302
TI  - Clinical study replicability and the pursuit of excellence.
AB  - Comparisons of processes of care are common in critical care research. Often,
      these processes are neither explicit nor replicable and this can result in
      seemingly irreconcilable results. Here, we briefly review the article by
      Taniguchi and colleagues, who studied liberation from mechanical ventilation by
      using either a computerized weaning protocol or one driven by respiratory
      therapists. We discuss the implications of explicit protocols increasing
      replicability in clinical research. 

PMID- 26299303
TI  - A SERS active bimetallic core-satellite nanostructure for the ultrasensitive
      detection of Mucin-1.
AB  - In this study, we established gold nanorods (Au NRs) core-silver nanoparticles
      (Ag NPs) satellite assemblies as an ultrasensitive aptamer-based SERS sensor for
      the detection of Mucin-1, a specific breast cancer marker protein. The limit of
      detection (LOD) was 4.3 aM and the wide linear range was 0.005-1 fM. 

PMID- 26299304
TI  - Photo-induced cation translocation in a molecular shuttle based on a calix[4]
      biscrown including DCM and DMABN chromophores.
AB  - We present a new molecular shuttle, consisting of a calixarene core attached to
      two different photoactive centers, DCM and DMABN. We show that a K(+) ion bound
      to the DCM-grafted crown is translocated towards the other site of the molecule
      upon photoexcitation, but not released to the bulk. 

PMID- 26299305
TI  - Colchicine induces apoptosis in HT-29 human colon cancer cells via the AKT and c
      Jun N-terminal kinase signaling pathways.
AB  - Colchicine is a natural compound, which belongs to the botanical family
      Colchicaceae and prevents growth of cancer cells via antimitotic activity by
      interacting with microtubules. Although numerous studies have demonstrated that
      the effect of colchicine on cell apoptosis is mediated by the activation of
      caspase-3, the signaling pathways involved in the process remain unknown. In the
      current study, evidence is presented regarding the missing information using HT
      29 human colon cancer cells. The effect of colchicine on apoptosis in HT-29 cells
      and the apoptosis-associated signaling pathways were determined using various
      methods, including cell viability assay, Annexin V/propidium idodide (PI)
      binding, PI staining, Hoechst 33342 staining, mitochondrial membrane potential
      (Deltapsim) assay, reactive oxygen species (ROS) assay and western blot analysis.
      Colchicine was observed to induce a dose-dependent reduction in cell viability in
      HT-29 cells and early apoptosis occurred when the cells were treated with 1 ug/ml
      colchicine. Furthermore, colchicine treatment induced a loss of Deltapsim,
      increased ROS production, activated caspase-3, upregulated BAX expression and
      downregulated Bcl-2 expression, which evidenced the colchicine activity on
      apoptosis, potentially by acting via the intrinsic apoptotic signaling pathway.
      Colchicine increased phosphorylation of p38, although not phosphorylation of
      extracellular signal-regulated kinase and c-Jun N-terminal kinase, which
      indicates that colchicine activates the p38 signaling pathway in order to induce
      cell apoptosis. Therefore, colchicine exhibited significant growth inhibition of
      the HT-29 colon cancer cell line and induced apoptosis in the cells via the
      mitochondrial pathway, which is regulated by p38 signaling pathways.

PMID- 26299307
TI  - Higher fluorescence in platinum(iv) orthometallated complexes of perylene imine
      compared with their platinum(ii) or palladium(ii) analogues.
AB  - The reaction of 3-perylenylmethylen-4'-ethylaniline () with [Pt2Me4(MU-SMe2)2]
      (and subsequent addition of PPh3) or with [Pt2(eta(3)-C4H7)2(MU-Cl)2] produced
      cyclometallated Pt(II) complexes [Pt(C^N)Me(PPh3)] () and, respectively,
      [Pt2(C^N)2(MU-Cl)2] () (HC^N = 3-C20H11CH[double bond, length as m-dash]NC6H4-p
      C2H5), with Pt bound to the ortho site of the perylenyl fragment. From the
      mononuclear complexes [Pt(C^N)L2] (L2 = acac (); S2COMe (); S2CNEt2 () are easily
      formed. Oxidative addition of methyl iodide to the square-planar Pt(II) complexes
      , , and gave the corresponding cyclometallated Pt(IV) compounds [Pt(C^N)L2MeI] ,
      and . The X-ray structures of , , and show that the perylenyl fragment remains
      essentially flat in and and slightly twisted in . Comparison of the optical
      properties of these Pt(II) complexes with those reported for similar Pd(II)
      derivatives reveals that the change of metal exerts a notable influence on the UV
      vis spectra. In solution at room temperature, all the Pt complexes exhibit
      fluorescence associated with the perylene fragment with low emission quantum
      yields for the Pt(II) complexes (<1%) and remarkably higher emission values for
      the Pt(IV) complexes: up to 29%, with emission lifetimes of 1-5 ns. Time
      dependent density functional theory (TD-DFT) calculations were performed on the
      perylene imine and on representative complexes [M(C^N)(acac)] (M = Pd, Pt) and
      [Pt(C^N)(acac)MeI] to analyse the absorption spectra. These calculations support
      a perylene-dominated intraligand pi-pi*emissive state based on the HOMO and LUMO
      orbitals of the perylene chromophore, and a ligand-to-ligand charge-transfer
      (more intense for the Pt(II) complex) that explains the observed influence of the
      metal on the absorption properties. 

PMID- 26299306
TI  - Parity and Cardiovascular Disease Mortality: a Dose-Response Meta-Analysis of
      Cohort Studies.
AB  - Parity has been shown to inversely associate with cardiovascular disease (CVD)
      mortality, but the evidence of epidemiological studies is still controversial.
      Therefore, we quantitatively assessed the relationship between parity and CVD
      mortality by summarizing the evidence from prospective studies. We searched
      MEDLINE (PubMed), EMBASE and ISI Web of Science databases for relevant
      prospective studies of parity and CVD mortality through the end of March 2015.
      Fixed- or random-effects models were used to estimate summary relative risks
      (RRs) and 95% confidence intervals (CIs). Heterogeneity among studies was
      assessed using the I(2) statistics. All statistical tests were two-sided. Ten
      prospective studies were included with a total of 994,810 participants and 16,601
      CVD events. A borderline significant inverse association was observed while
      comparing parity with nulliparous, with summarized RR = 0.79 (95% CI: 0.60-1.06;
      I(2) = 90.9%, P < 0.001). In dose-response analysis, we observed a significant
      nonlinear association between parity number and CVD mortality. The greatest risk
      reduction appeared when the parity number reached four. The findings of this meta
      analysis suggests that ever parity is inversely related to CVD mortality.
      Furthermore, there is a statistically significant nonlinear inverse association
      between parity number and CVD mortality. 

PMID- 26299308
TI  - Electrochemical reduction of CO2 to ethylene glycol on imidazolium ion-terminated
      self-assembly monolayer-modified Au electrodes in an aqueous solution.
AB  - Imidazolium ion-terminated self-assembled monolayer (SAM)-modified electrodes
      achieve CO2 conversion while suppressing hydrogen evolution. Immobile imidazolium
      ion on gold (Au) electrodes reduce CO2 at low overpotential. The distance between
      electrode and imidazolium ion separated by alkane thiol affects CO2 reduction
      activity. CO2 reduction current depends on the tunnel current rate. Although the
      product of CO2 reduction at the bare Au electrode is CO, SAM-modified electrodes
      produce ethylene glycol in aqueous electrolyte solution without CO evolution. The
      faradaic efficiency reached a maximum of 87%. CO2 reduction at SAM-modified
      electrodes is unaffected by reduction activity of Au electrode. This phenomenon
      shows that the reaction field of CO2 reduction is not the electrode surface but
      the imidazolium ion monolayer. 

PMID- 26299309
TI  - Tbx15 controls skeletal muscle fibre-type determination and muscle metabolism.
AB  - Skeletal muscle is composed of both slow-twitch oxidative myofibers and fast
      twitch glycolytic myofibers that differentially impact muscle metabolism,
      function and eventually whole-body physiology. Here we show that the mesodermal
      transcription factor T-box 15 (Tbx15) is highly and specifically expressed in
      glycolytic myofibers. Ablation of Tbx15 in vivo leads to a decrease in muscle
      size due to a decrease in the number of glycolytic fibres, associated with a
      small increase in the number of oxidative fibres. This shift in fibre composition
      results in muscles with slower myofiber contraction and relaxation, and also
      decreases whole-body oxygen consumption, reduces spontaneous activity, increases
      adiposity and glucose intolerance. Mechanistically, ablation of Tbx15 leads to
      activation of AMPK signalling and a decrease in Igf2 expression. Thus, Tbx15 is
      one of a limited number of transcription factors to be identified with a critical
      role in regulating glycolytic fibre identity and muscle metabolism. 

PMID- 26299310
TI  - Investigation of Inhibition Mechanism of Chemokine Receptor CCR5 by Micro-second
      Molecular Dynamics Simulations.
AB  - Chemokine receptor 5 (CCR5) belongs to G protein coupled receptors (GPCRs) and
      plays an important role in treatment of human immunodeficiency virus (HIV)
      infection since HIV uses CCR5 protein as a co-receptor. Recently, the crystal
      structure of CCR5-bound complex with an approved anti-retroviral drug (maroviroc)
      was resolved. During the crystallization procedure, amino acid residues (i.e.,
      Cys224, Arg225, Asn226 and Glu227) at the third intra-cellular loop were replaced
      by the rubredoxin for stability reasons. In the current study, we aimed to
      understand the impact of the incorporated rubredoxin on the conformations of TM
      domains of the target protein. For this reason, rubredoxin was deleted from the
      crystal structure and the missing amino acids were engineered. The resultant
      structure was subjected to long (MUs) molecular dynamics (MD) simulations to shed
      light into the inhibitory mechanism. The derived model structure displayed a
      significant deviation in the cytoplasmic domain of TM5 and IC3 in the absence of
      rubredoxin. The principal component analyses (PCA) and MD trajectory analyses
      revealed important structural and dynamical differences at apo and holo forms of
      the CCR5. 

PMID- 26299311
TI  - Anxiety symptoms in Korean elderly individuals: a two-year longitudinal community
      study.
AB  - BACKGROUND: Although late-life anxiety occurs frequently and is associated with
      higher morbidity, few longitudinal studies have been concerned with the
      evaluation thereof. We investigated the prevalence, incidence, and persistence of
      anxiety and related factors over a two-year period in community-dwelling Korean
      elderly individuals. METHODS: A total of 1,204 Korean elderly individuals were
      evaluated at baseline, and 909 were followed up two years later. The community
      version of the Geriatric Mental State Schedule was used to estimate anxiety at
      both baseline and follow-up interviews. We defined "prevalence" as the rate of
      anxiety symptoms (for both anxiety cases and sub-threshold anxiety) at baseline;
      "incidence" as the rate of anxiety symptoms at follow-up in those without
      baseline anxiety symptoms; and "persistence" as the rate of anxiety symptoms at
      follow-up in those with baseline anxiety symptoms. Associations between various
      covariates and anxiety status were examined using multivariate logistic
      regression models. RESULTS: The prevalence, incidence, and persistence of anxiety
      symptoms were 38.1%, 29.3%, and 41.1%, respectively. Prevalent anxiety symptoms
      were associated independently with female, rented housing, more stressful life
      event and medical illness, physical inactivity, depression, insomnia, and lower
      cognitive function. Incident anxiety symptoms were predicted by older age, female
      gender, depression, and insomnia; persistent anxiety symptoms were predicted by
      older age, more medical illness, and baseline depression. CONCLUSIONS: Since
      depression was associated with prevalent, incident, and persistent anxiety
      symptoms, effective detection and management thereof is important in older adults
      to reduce anxiety. Furthermore, preventive collaborative care should be
      considered, particularly for older, female, insomniac patients.

PMID- 26299312
TI  - Nesfatin-1 acts on the dopaminergic reward pathway to inhibit food intake.
AB  - Nesfatin-1 is a novel 82-amino acid anorectic peptide. Previous studies of
      nesfatin-1 have focused on hypothalamic and brainstem circuits implicated in
      feeding regulation. Recently, nesfatin-1 expression was also reported in the
      nucleus accumbens (NAc), amygdaloid nucleus and insular cortex of mice, areas
      that are related to the control of reward behavior. Therefore, it is possible
      that nesfatin-1 might also inhibit food intake via central reward circuits. Using
      electrophysiology and electrochemical and behavioral tests, we investigated the
      effect of nesfatin-1 on the dopaminergic reward pathway between the ventral
      tegmental area (VTA) and the NAc. Our results showed that injection of nesfatin-1
      into the VTA significantly inhibited dark-phase cumulative food intake in mice.
      The excitability of VTA dopaminergic neurons was inhibited by nesfatin-1. In
      addition, nesfatin-1 decreased dopamine release in the NAc. Therefore, we
      concluded that nesfatin-1 acts on dopaminergic neurons, and these effects might
      contribute to the decrease of food intake that results from the injection of
      nesfatin-1 into the VTA. 

PMID- 26299313
TI  - Functionalization of nanomaterials with aryldiazonium salts.
AB  - This paper reviews the surface modification strategies of a wide range of
      nanomaterials using aryldiazonium salts. After a brief history of diazonium salts
      since their discovery by Peter Griess in 1858, we will tackle the surface
      chemistry using these compounds since the first trials in the 1950s. We will then
      focus on the modern surface chemistry of aryldiazonium salts for the modification
      of materials, particularly metallic, semiconductors, metal oxide nanoparticles,
      carbon-based nanostructures, diamond and clays. The successful modification of
      sp(2) carbon materials and metals by aryldiazonium salts paved the way to
      innovative strategies for the attachment of aryl layers to metal oxide
      nanoparticles and nanodiamonds, and intercalation of clays. Interestingly,
      diazotized surfaces can easily trap nanoparticles and nanotubes while diazotized
      nanoparticles can be (electro)chemically reduced on electrode/materials surfaces
      as molecular compounds. Both strategies provided organized 2D surface assembled
      nanoparticles. In this review, aryldiazonium salts are highlighted as efficient
      coupling agents for many types of molecular, macromolecular and nanoparticulate
      species, therefore ensuring stability to colloids on the one hand, and the
      construction of composite materials and hybrid systems with robust and durable
      interfaces/interphases, on the other hand. The last section is dedicated to a
      selection of patents and industrial products based on aryldiazonium-modified
      nanomaterials. After nearly 160 years of organic chemistry, diazonium salts have
      entered a new, long and thriving era for the benefit of materials, colloids, and
      surface scientists. This tempts us to introduce the terminology of "diazonics" we
      define as the science and technology of aryldiazonium salt-derived materials.

PMID- 26299315
TI  - Age Differences in Treatment and Control of Hypertension in US Physician Offices,
      2003-2010: A Serial Cross-sectional Study.
AB  - BACKGROUND: Evidence-based and age-appropriate antihypertensive pharmacotherapy
      in outpatient settings is essential for optimal treatment outcomes. Recent
      guidelines, although controversial, recommended different blood pressure goals
      using age cutoff of 60 years. We describe recent age-specific national trends in
      antihypertensive prescribing patterns and blood pressure control in US office
      based practices. METHODS: We analyzed all hypertension-related visits to
      physician offices from the latest available National Ambulatory Medical Care
      Survey (2003-2010). We identified trends of antihypertensive prescribing overall
      and by class, trends of hypertension control, age differences in antihypertensive
      prescribing patterns and hypertension control, predicted probabilities of
      hypertension control in subgroups, and correlates of hypertension control.
      RESULTS: There were 16,729 physician office visits included in the analysis.
      Overall, the prescription of antihypertensive medication increased from 69.2% in
      2003-2004 to 78.8% in 2009-2010 (Ptrend = .001), and the increased trend was
      consistent in both age groups (<60 and >=60 years). This was accompanied by an
      improvement in the overall hypertension control (from 39.1% to 48.8%, Ptrend
      <.001). Antihypertensive prescribing patterns differ significantly between the 2
      age groups. The proportions of visits with beta-blocker (from 25.4% to 34.7%,
      Ptrend <.001) and angiotensin receptor blocker prescriptions (from 17.0% to
      22.1%, Ptrend = .042) increased for older patients. The increased trend of beta
      blocker use persisted after excluding patients with compelling indications. Among
      treated patients, lower odds of blood pressure control were associated with
      African American race, presence of comorbidities, younger age, and insufficient
      insurance coverage. CONCLUSIONS: In office-based practices, antihypertensive
      medication prescribing among US adults with hypertension increased significantly
      in recent years, which was accompanied by improvement in hypertension control.
      The prescribing patterns differed among younger and older patients, but
      continuous use of beta-blockers without other compelling indications raises
      concerns.

PMID- 26299314
TI  - Intrinsic brain indices of verbal working memory capacity in children and
      adolescents.
AB  - Working memory (WM) is central to the acquisition of knowledge and skills
      throughout childhood and adolescence. While numerous behavioral and task-based
      functional magnetic resonance imaging (fMRI) studies have examined WM
      development, few have used resting-state fMRI (R-fMRI). Here, we present a
      systematic R-fMRI examination of age-related differences in the neural indices of
      verbal WM performance in a cross-sectional pediatric sample (ages: 7-17; n=68),
      using data-driven approaches. Verbal WM capacity was measured with the digit span
      task, a commonly used educational and clinical assessment. We found distinct
      neural indices of digit span forward (DSF) and backward (DSB) performance,
      reflecting their unique neuropsychological demands. Regardless of age, DSB
      performance was related to intrinsic properties of brain areas previously
      implicated in attention and cognitive control, while DSF performance was related
      to areas less commonly implicated in verbal WM storage (precuneus, lateral visual
      areas). From a developmental perspective, DSF exhibited more robust age-related
      differences in brain-behavior relationships than DSB, and implicated a broader
      range of networks (ventral attention, default, somatomotor, limbic networks)-
      including a number of regions not commonly associated with verbal WM (angular
      gyrus, subcallosum). These results highlight the importance of examining the
      neurodevelopment of verbal WM and of considering regions beyond the "usual
      suspects".

PMID- 26299316
TI  - Misconceptions and Facts About Hypertrophic Cardiomyopathy.
AB  - Hypertrophic cardiomyopathy is the most common genetic heart disease. Once
      considered relentless, untreatable, and deadly, it has become a highly treatable
      disease with contemporary management. Hypertrophic cardiomyopathy is one of
      cardiology's "great masqueraders." Mistakes and delays in diagnosis abound.
      Hypertrophic cardiomyopathy commonly "masquerades" as asthma, anxiety, mitral
      prolapse, and coronary artery disease. However, once properly diagnosed, patients
      with hypertrophic cardiomyopathy can be effectively managed to improve both
      symptoms and survival. This review highlights some of the misconceptions about
      hypertrophic cardiomyopathy. Providers at all levels should have awareness of
      hypertrophic cardiomyopathy to promptly diagnose and properly manage these
      individuals. 

PMID- 26299317
TI  - Grapefruit Juice and Statins.
AB  - We determined the validity of current medical advice to avoid grapefruit juice
      consumption while taking 3 widely used statins. A daily glass of grapefruit juice
      increases blood levels of simvastatin and lovastatin by about 260% if taken at
      the same time (about 90% if taken 12 hours apart), and atorvastatin by about 80%
      (whenever taken). Simvastatin 40 mg, lovastatin 40 mg, and atorvastatin 10 mg
      daily reduce low-density lipoprotein (LDL) cholesterol levels in a 60-year-old
      man with an LDL cholesterol of 4.8 mmol/L by 37%, reducing ischemic heart disease
      risk by 61%. When simvastatin or lovastatin are taken at the same time as
      grapefruit juice, the estimated reduction in LDL cholesterol is 48%, and in heart
      disease is 70%. If the juice is taken 12 hours before these statins, the
      reductions are, respectively, 43% and 66%, and for atorvastatin, 42% and 66%. The
      increased rhabdomyolysis risk from grapefruit juice consumption due to the
      increased effective statin dose is minimal compared with the greater effect in
      preventing heart disease. Grapefruit juice should not be contraindicated in
      people taking statins. 

PMID- 26299318
TI  - Negative Secular Trends in Medicine: Prolonged Training Periods.

PMID- 26299319
TI  - The Incidence and Outcomes of Ischemic Hepatitis: A Systematic Review with Meta
      analysis.
AB  - BACKGROUND: Ischemic hepatitis is a devastating cause of acute liver injury. Data
      are limited regarding its incidence and outcomes. METHODS: Systematic review and
      meta-analysis of studies from PubMed, EMBASE, and Web of Science with specific
      search terms. Inclusion criteria included case series with >10 patients and clear
      case definition (especially liver enzyme levels >10 times the upper limit of
      normal). RESULTS: Twenty-four papers met inclusion criteria. A total of 1782
      cases were identified in these papers (mean 78 per paper, range 12-322). The
      pooled average age of the included patients was 64.2 years, and their mean peak
      aspartate aminotransferase level, alanine aminotransferase level, and total
      bilirubin were 2423 IU/L, 1893 IU/L, and 2.55 mg/dL, respectively. Ischemic
      hepatitis was present in 2 of every 1000 admissions; including 2.5 of every 100
      intensive care unit admissions and 4 of 10 admissions associated with an
      aminotransferase level >10 times the upper limit of normal. The pooled
      proportions of patients with ischemic hepatitis who had a predisposing acute
      cardiac event or sepsis were 78.2% and 23.4%, respectively. The proportion of
      patients with a documented hypotensive event of any duration was 52.9%. Overall,
      the pooled rate of survival to discharge was 51% (range 23.1%-85.7%).
      CONCLUSIONS: Ischemic hepatitis is a common cause of severe acute liver injury
      and is associated with a significant risk of in-hospital death. A major
      opportunity in the management of ischemic hepatitis is recognition of the
      condition without documented hypotension.

PMID- 26299320
TI  - Demolition Site: Rhinotillexomania.

PMID- 26299321
TI  - Not Just Another Flare: Acute Polyarthritis in Rheumatoid Arthritis.

PMID- 26299322
TI  - Caught on Capsule: Iron-deficiency Anemia Due to Hookworm Infection.

PMID- 26299323
TI  - Focal nodular hyperplasia and hepatocellular adenoma: The value of shear wave
      elastography for differential diagnosis.
AB  - OBJECTIVE: This study assessed the clinical usefulness of shear wave elastography
      (SWE) during ultrasound for differentiating between focal nodular hyperplasias
      (FNHs) and hepatocellular adenomas (HAs). MATERIALS AND METHODS: SWE was
      performed on 56 patients presenting with 76 liver lesions (57 FNHs and 19HAs)
      that were confirmed by MRI and contrast-enhanced ultrasound (CEUS) (n=55) or by
      histology (n=21). A mean elasticity value was obtained for each lesion. The
      ratios of the elasticity of the lesions to the elasticity of the surrounding
      liver were determined. The optimal elasticity cut-off value for distinguishing
      between the two lesion types was determined using ROC analysis. All lesions that
      were classified as "undetermined" after CEUS were reclassified using the
      elasticity values. RESULTS: The mean elasticity value was 46.99 +/- 31.15 kPa for
      FNHs and 12.08 +/- 10.68 kPa for HAs (p<0.0001). The mean relative elasticity
      ratio values were 7.94 +/- 6.43 and 1.91 +/- 1.70, respectively (p<0.0001). The
      ROC analysis showed a maximal accuracy of 95% for identification with a cut-off
      of 18.8 kPa for lesion elasticity (accuracy of 96% with a cut-off of 1.98 for the
      relative elasticity ratio). A total of 68 CEUS were performed, and 17 lesions
      (25%) were classified as "undetermined" after CEUS. With these cut-off values 16
      lesions (94.1%) were correctly reclassified as FNHs. CONCLUSION: SWE is a useful
      adjunctive tool for differentiation between FNH and HA during ultrasound
      examination.

PMID- 26299324
TI  - Intraoperative intravenous lidocaine exerts a protective effect on cell-mediated
      immunity in patients undergoing radical hysterectomy.
AB  - Surgical procedures cause a decrease in lymphocyte proliferation rate, an
      increase in apoptosis and shifts the balance of T-helper (Th)1/Th2 cells towards
      anti-cell-mediated immunity (CMI) Th2 dominance, which is relevant to the
      immunosuppressive effects of CMI, postoperative septic complications and the
      formation of tumor metastasis. Previous studies have revealed that lidocaine
      exhibits antibacterial actions; regulating inflammatory responses, reducing
      postoperative pain and affecting the duration spent in hospital. Thus, the
      present study hypothesized that lidocaine may exert a protective effect on the
      CMI of patients undergoing surgery for the removal of a primary tumor. A total of
      30 adult female patients diagnosed with cervical cancer were recruited to the
      present study and were randomized into two groups. The lidocaine group received
      an intravenous bolus dose of 1.5 mg/kg lidocaine, followed by continuous infusion
      at 1.5 mg/kg/h until discharge from the operating room. The control group
      received the same volume of normal saline. A 10 ml sample of venous blood was
      drawn, and the lymphocytes were isolated using Ficoll-paque 1 day prior to
      surgery, at discharge from the operating room and 48 h post-surgery. The
      proliferation rate of the lymphocytes was assessed using a Cell Counting Kit-8
      assay and was found to be higher in the lidocaine group. The early apoptosis of
      lymphocytes was attenuated following lidocaine treatment at 48 h post-surgery, as
      detected using flow cytometry with Annexin V-fluorescein isothiocyanate/propidium
      iodide staining. The level of interferon (IFN)-gamma in the serum at 48 h was
      significantly decreased following surgery in the control group, compared with the
      pre-surgical values (3.782 +/- 0.282, vs. 4.089 +/- 0.339 pg/ml, respectively)
      and the ratio of IFN-gamma to interleukin-4 was well preserved in the lidocaine
      group. In conclusion, the present study demonstrated that the intraoperative
      systemic administration of lidocaine exerted a protective effect on CMI in
      patients with cervical cancer undergoing radical hysterectomy. This may be
      beneficial in reducing the occurrence of postoperative septic complications and
      tumor metastasis formation.

PMID- 26299325
TI  - Can hip abduction and external rotation discriminate sacroiliac joint pain?
AB  - AIM: The primary aim of the study is to determine if Hip Abduction and External
      Rotation (HABER) test is capable of reproducing familiar pain in individuals with
      low back pain (LBP) of sacroiliac joint (SIJ) origin (SIJ-positive) when compared
      with LBP of Non-SIJ origin (SIJ-negative). If so, the secondary aim is to
      determine the diagnostic accuracy of HABER test against the reference standard of
      pain provocation tests, and to determine which increments of the HABER test has
      highest sensitivity and specificity for identifying SIJ-positive individuals.
      DESIGN: Single-blinded diagnostic accuracy study. METHOD: Participants [n(122)]
      between ages of 18-50 y, suffering from chronic non-specific LBP (>=3 months)
      volunteered in the study. An experienced musculoskeletal physiotherapist
      evaluated and classified participants into either SIJ-positive [n(45)] or SIJ
      negative [n(77)], based on reference standard of pain provocation tests [>=3
      positive tests = SIJ-positive]. Another musculoskeletal physiotherapist, blinded
      to clinical groups, evaluated participants for reproduction of familiar pain
      during each increment (10 degrees , 20 degrees , 30 degrees , 40 degrees , and 50
      degrees ) of HABER test. RESULTS: The HABER test reproduced familiar pain in SIJ
      positive individuals when compared with SIJ-negative individuals [p (0.001), R(2)
      (0.38), Exp(beta) (5.95-10.32)], and demonstrated moderate level of sensitivity
      (67%-78%) and specificity (71%-72%) for identifying SIJ-positive individuals.
      Receiver operator curve analysis demonstrated that the HABER increments of >=30
      degrees  have the highest sensitivity (83%-100%) and specificity (52%-64%).
      CONCLUSIONS: The HABER test is capable of reproducing familiar pain in SIJ
      positive LBP individuals and has moderate levels of sensitivity and specificity
      for identifying SIJ-positive LBP individuals.

PMID- 26299326
TI  - Anticancer drugs induce hypomethylation of the acetylcholinesterase promoter via
      a phosphorylated-p38-DNMT1-AChE pathway in apoptotic hepatocellular carcinoma
      cells.
AB  - Apoptosis, also known as programmed cell death, plays an essential role in
      eliminating excessive, damaged or harmful cells. Previous work has demonstrated
      that anticancer drugs induce cell apoptosis by inducing cytotoxicity. In recent
      years, several reports demonstrated modulated expression of DNA
      methyltransferases 1 (DNMT1) and acetylcholinesterase (AChE) in a variety of
      tumors. In this study, we showed that the expression of DNMT1 was decreased and
      the methylation of CpGs in the promoter of AChE was reduced in anticancer drugs
      induced apoptotic hepatocellular carcinoma cells. Silencing of DNMT1 expression
      by AZA or RNA interference (RNAi) restored AChE production and inhibition of AChE
      expression by RNAi protected HCC cells from anticancer drugs-induced apoptosis.
      Furthermore, we demonstrated that the regulation of AChE by DNMT1 was involved in
      the phosphorylated p38 pathway in anticancer drugs-induced apoptosis. In
      addition, immunohistochemical staining showed that P-p38, DNMT1 and AChE were
      aberrantly expressed in a subset of HCC tumors. Taken together, we demonstrated
      the regulation of AChE by DNMT1 and further, we found that this regulation was
      involved in the phosphorylated p38 pathway in anticancer drugs-induced apoptosis.

PMID- 26299327
TI  - Estrogen receptor signal in regulation of B cell activation during diverse immune
      responses.
AB  - The role of signalling through oestrogen receptors (ERs) in the regulation of B
      cell activation is an area of growing importance not only in terms protective
      immunity but also in the determination of the mechanisms of the onset of
      autoimmune disorders and cancers. The mode of signalling action of this single
      chain nuclear receptor protein molecule depends on its ability to bind to the
      promoters of Pax5, HOXC4 and apolipoprotein B RNA-editing enzyme activation
      induced cytidine deaminase (AID) genes. ER-mediated transcriptional regulation
      induces class switch recombination of the immunoglobulin heavy chain variable
      (VH) to DH-JH genes and somatic hypermutation in developing B cells. The mode of
      action of ER is associated with BCR-signal pathways that involve the regulator
      proteins BAFF and APRIL. Additionally, the plasma membrane-bound G protein
      coupled oestrogen receptor-1 (GEPR1) directs diverse cell signalling events in B
      cells that involve the MAPK pathways. These signals are immensely important
      during progenitor and precursor B cell activation. We have focused our goals on
      the medicinal aspects of ER-signalling mechanisms and their effects on polyclonal
      B cell activation. 

PMID- 26299328
TI  - Let-7g induces granulosa cell apoptosis by targeting MAP3K1 in the porcine ovary.
AB  - Follicular atresia mainly results from apoptosis of granulosa cells (GCs). Our
      previous microRNA array data indicated that the miRNA let-7g level increases
      significantly during porcine ovary follicular atresia. It is uncertain if GCs
      apoptosis is mediated by microRNA let-7g. In this study, the expression levels of
      the apoptosis-associated genes CASP3, BAX and BIM were significantly upregulated
      when let-7g mimic was transfected into porcine GCs, and the anti-apoptotic genes
      BCL-2 and MCL-1 were significantly downregulated. The apoptosis rate was measured
      by flow cytometry, and our results indicated that let-7g significantly enhanced
      GCs apoptosis. In further studies, we found that overexpression of let-7g induced
      the expression of FoxO1 in GCs and led to nuclear accumulation of
      dephosphorylated FoxO1. In addition, the effect of let-7g on FoxO1 expression and
      dephosphorylation resulted from repression of the expression of the MAP3K1 gene
      in porcine GCs. The site on MAP3K1 mRNA targeted by let-7g was confirmed by
      luciferase reporter assay. The anti-apoptotic effect of MAP3K1 was validated by
      silencing MAP3K1 using small interfering RNA technology. In conclusion, our data
      indicate that let-7g induces porcine GCs apoptosis by inhibiting the MAP3K1 gene,
      which promotes FoxO1 expression and dephosphorylation with nuclear accumulation. 

PMID- 26299329
TI  - Regulation of MDA5-MAVS Antiviral Signaling Axis by TRIM25 through TRAF6-Mediated
      NF-kappaB Activation.
AB  - Tripartite motif protein 25 (TRIM25), mediates K63-linked polyubiquitination of
      Retinoic acid inducible gene I (RIG-I) that is crucial for downstream antiviral
      interferon signaling. Here, we demonstrate that TRIM25 is required for melanoma
      differentiation-associated gene 5 (MDA5) and MAVS mediated activation of NF
      kappaB and interferon production. TRIM25 is required for the full activation of
      NF-kappaB at the downstream of MAVS, while it is not involved in IRF3 nuclear
      translocation. Mechanical studies showed that TRIM25 is involved in TRAF6
      mediated NF-kappaB activation. These collectively indicate that TRIM25 plays an
      additional role in RIG-I/MDA5 signaling other than RIG-I ubiquitination via
      activation of NF-kappaB. 

PMID- 26299331
TI  - LPS Up-Regulates ICAM-1 Expression in Breast Cancer Cells by Stimulating a MyD88
      BLT2-ERK-Linked Cascade, Which Promotes Adhesion to Monocytes.
AB  - Monocytes are the major inflammatory cells that infiltrate most solid tumors in
      humans. The interaction of tumor cells with infiltrating monocytes and their
      adhesion to these monocytes play a significant role in altering the tumor to
      become more aggressive. Recently, exposure to lipopolysaccharide (LPS) was
      suggested to promote cancer cell adhesion to monocytes; however, little is known
      about the details of the signaling mechanism involved in this process. In this
      study, we found that LPS up-regulates ICAM-1 expression in MDA-MB-231 breast
      cancer cells, which facilitates their adhesion to THP-1 monocytes. In addition,
      we analyzed the signaling mechanism underlying the up-regulation of ICAM-1 and
      found that the siRNA-mediated depletion of BLT2 markedly suppressed the LPS
      induced expression of ICAM-1 in MDA-MB-231 cells and the subsequent adhesion of
      these cells to THP-1 monocytes. Moreover, we demonstrated that myeloid
      differentiation primary response gene 88 (MyD88) lies downstream of LPS/TLR4 and
      upstream of BLT2 and that this 'MyD88-BLT2' cascade mediates ERK activation and
      subsequent ICAM-1 expression, which is critical for the adhesion of MDA-MB-231
      cells to THP-1 monocytes. Taken together, our results demonstrate for the first
      time that LPS up-regulates ICAM-1 expression in breast cancer cells via a MyD88
      BLT2-ERK-linked signaling cascade, leading to the increased adhesion of breast
      cancer cells to monocytes. 

PMID- 26299330
TI  - The Genome-Wide Expression Profile of Saussurea lappa Extract on House Dust Mite
      Induced Atopic Dermatitis in Nc/Nga Mice.
AB  - Saussurea lappa has been reported to possess anti-atopic properties. In this
      study, we have confirmed the S. lappa's anti-atopic properties in Nc/Nga mice and
      investigated the candidate gene related with its properties using microarray. We
      determined the target gene using real time PCR in in vitro experiment. S. lappa
      showed the significant reduction in atopic dermatitis (AD) score and
      immunoglobulin E compared with the AD induced Nc/Nga mice. In the results of
      microarray using back skin obtained from animals, we found that S. lappa's
      properties are closely associated with cytokine-cytokine receptor interaction and
      the JAK-STAT signaling pathway. Consistent with the microarray data, real-time RT
      PCR confirmed these modulation at the mRNA level in skin tissues from S. lappa
      treated mice. Among these genes, PI3Kca and IL20Rbeta were significantly
      downregulated by S. lappa treatment in Nc/Nga mouse model. In in vitro experiment
      using HaCaT cells, we found that the S. lappa components, including
      alantolactone, caryophyllene, costic acid, costunolide and dehydrocostus lactone
      significantly decreased the expression of PI3Kca but not IL20Rbeta in vitro.
      Therefore, our study suggests that PI3Kca-related signaling is closely related
      with the protective effects of S. lappa against the development of atopic
      dermatitis.

PMID- 26299332
TI  - Dietary acid load, metabolic acidosis and insulin resistance - Lessons from cross
      sectional and overfeeding studies in humans.
AB  - BACKGROUND & AIM: Western diets rich in animal protein and poor in fruit and
      vegetables increase the body acid load, a predictor of type 2 diabetes risk. The
      relationships between dietary acid load, mild metabolic acidosis and insulin
      resistance remain unclear. The objective of this study was to assess the
      association between dietary acid load, body acid/base markers and peripheral
      insulin resistance at baseline and following a short-term overfeeding
      intervention in healthy individuals. METHODS: In a cross-sectional study of 104
      men and women, insulin sensitivity was measured by hyperinsulinemic-euglycemic
      clamp. Plasma lactate, a marker of metabolic acidosis, was assessed and acid load
      scores (potential renal acid load, PRAL and net endogenous acid production, NEAP)
      derived from diet diaries. The cohort was grouped into lean and overweight/obese
      and the latter further classified as insulin-sensitive (Obsen) and insulin
      resistant (Obres) based on hyperinsulinemic-euglycemic clamp glucose infusion
      rate (GIR, top tertile vs. bottom 2 tertiles). A subset of 40 individuals
      participated in an overfeeding intervention (+1250 kcal/day) for 28 days and
      studies repeated. RESULTS: Obsen and Obres were matched for adiposity (BMI and
      fat mass, both P = 1). Fasting plasma lactate was higher in Obres (0.78 [0.63
      1.14] mmol/L) compared with both lean (0.71 [0.44-0.90] mmol/L, P = 0.02) and
      Obsen (0.67 [0.56-0.79] mmol/L, P = 0.04) and not different between lean and
      Obsen (P = 0.9). Overfeeding was characterized by an increase in dietary acid
      load scores PRAL (P = 0.003) and NEAP (P = 0.05), a reduction in GIR necessary to
      maintain euglycemia (P = 0.03) and an increase in fasting plasma lactate (P =
      0.02). The change in lactate was inversely associated with the change in GIR (r =
      -0.36, P = 0.03). CONCLUSIONS: Mild metabolic acidosis, measured by plasma
      lactate, aligns with insulin resistance independent of obesity and is induced by
      short-term increases in energy and dietary acid load in healthy humans. Further
      studies are required to determine whether buffering mild metabolic acidosis
      improves insulin resistance and reduces diabetes risk.

PMID- 26299334
TI  - Synthesis of trifluoromethyl gamma-aminophosphonates by nucleophilic aziridine
      ring opening.
AB  - Phosphonated derivatives of trifluoromethyl aziridine were obtained with good
      yield from aziridine-2-carbaldehyde by two distinct methods, which resulted in
      different diastereoselectivities. Using thiols as nucleophiles ring opening
      reactions of trifluoromethylated derivatives of aziridine-2-phosphonates
      proceeded regio- and diastereoselectively, giving rise to gamma-amino-gamma
      trifluoromethyl phosphonates. 

PMID- 26299333
TI  - Echocardiographic estimation of right ventricular stroke work in children with
      pulmonary arterial hypertension: comparison with invasive measurements.
AB  - BACKGROUND: Right ventricular (RV) failure is a key determinant of mortality in
      children with pulmonary arterial hypertension (PAH). RV stroke work (RVSW) can be
      estimated as the product of RV systolic pressure and stroke volume. The authors
      have shown that RVSW predicts adverse outcomes in this population when derived
      from hemodynamic data; noninvasive assessment of RVSW may be advantageous but has
      not been assessed. There are few data validating noninvasive versus invasive
      measurements in children with PAH. The aim of this study was to compare
      echocardiographically derived RVSW with RVSW determined from hemodynamic data.
      METHODS: This was a retrospective study, including subjects with idiopathic PAH
      and minor or repaired congenital heart disease. Forty-nine subjects were
      included, in whom cardiac catheterization and echocardiography were performed
      within 1 month. Fourteen additional patients were included in a separate cohort,
      in whom catheterization and echocardiography were performed simultaneously.
      Catheterization-derived RVSW was calculated as RV systolic pressure * (cardiac
      output/heart rate). Echocardiographically derived RVSW was calculated as 4 *
      (peak tricuspid regurgitant jet velocity)(2) * (pulmonary valve area * velocity
      time integral). Statistics included the intraclass correlation coefficient and
      Bland-Altman analysis. RESULTS: Echocardiographically derived RVSW was linearly
      correlated with invasively derived RVSW (r = 0.74, P < .0001, intraclass
      correlation coefficient = 0.76). Bland-Altman analysis showed adequate agreement.
      Echocardiographically derived RV work was related to indexed pulmonary vascular
      resistance (r = 0.43, P = .002), tricuspid annular plane systolic excursion (r =
      0.41, P = .004), and RV wall thickness (r = 0.62, P < .0001). CONCLUSIONS: The
      authors demonstrate that RV work, a potential novel index of RV function, can be
      estimated noninvasively and is related to pulmonary hemodynamics and other
      indices of RV performance.

PMID- 26299335
TI  - Metastatic clear cell renal cell carcinoma: A review of current therapies and
      novel immunotherapies.
AB  - Treatment of metastatic renal cell carcinoma (mRCC) has changed dramatically in
      the past 10 years, largely due to advances in understanding of tumor biology. A
      number of targeted therapies have been shown to improve progression free survival
      and overall survival as compared to nonspecific immunotherapy. Despite the
      success of targeted therapies, they have not produced durable responses that have
      been seen historically with immunotherapy such as IL-2 (interleukin 2) and IFN
      alpha (interferon). The promise of durable responses has caused some to shift
      research focus from targeted therapies to novel immunotherapies. This article
      reviews the literature behind the current targeted therapies and describes
      several novel approaches to immunotherapy that are in various phases of
      development. 

PMID- 26299336
TI  - How medical choices influence quality of life of women carrying a BRCA mutation.
AB  - Germline mutations in BRCA1 and BRCA2 genes were discovered twenty years ago.
      Female BRCA mutation carriers have an increased risk of breast and ovarian cancer
      at a relatively young age. Several choices have to be made with respect to cancer
      risk management, and consequences of these choices may affect quality of life. A
      review of the literature was performed to evaluate quality of life in unaffected
      BRCA mutation carriers and the influence of these medical choices. Overall,
      general quality of life appears not to be permanently affected in BRCA mutation
      carriers or by their choices. Risk-reducing salpingo-oophorectomy and its
      subsequent premature menopause affect (menopause specific) quality of life most.
      Hormone replacement therapy does not fully alleviate climacteric symptoms and
      therefore, there is a strong need for alternative strategies to reduce ovarian
      cancer risk and/or for improvements in postoperative care. Future research should
      focus on these needs. 

PMID- 26299337
TI  - Detection and some properties of a high molecular weight toxin in the
      hypobranchial gland of strawberry conch Strombus luhuanus.
AB  - The extract from the hypobranchial gland of strawberry conch Strombus luhuanus
      was found to be lethal to mice. There were no marked regional and seasonal
      variations in toxicity although a considerable individual variation was
      recognized. The toxin was thermostable and extractable with aqueous solvents but
      not with organic solvents. Behaviors in dialysis, ultrafiltration and column
      chromatography on various adsorbents suggested that the toxin is a high molecular
      weight acidic substance of 400-500 k.

PMID- 26299338
TI  - A previous history of repeated amphetamine exposure modifies brain angiotensin II
      AT1 receptor functionality.
AB  - Previous results from our laboratory showed that angiotensin II AT1 receptors
      (AT1-R) are involved in the neuroadaptative changes induced by amphetamine. The
      aim of the present work was to study functional and neurochemical responses to
      angiotensin II (ANG II) mediated by AT1-R activation in animals previously
      exposed to amphetamine. For this purpose male Wistar rats (250-320 g) were
      treated with amphetamine (2.5mg/kg/day intraperitoneal) or saline for 5 days and
      implanted with intracerebroventricular (i.c.v.) cannulae. Seven days after the
      last amphetamine administration the animals received ANG II (400 pmol) i.c.v. One
      group was tested in a free choice paradigm for sodium (2% NaCl) and water intake
      and sacrificed for Fos immunoreactivity (Fos-IR) determinations. In a second
      group of rats, urine and plasma samples were collected for electrolytes and
      plasma renin activity determination and then they were sacrificed for Fos-IR
      determination in Oxytocinergic neurons (Fos-OT-IR). RESULTS: Repeated amphetamine
      exposure (a) prevented the increase in sodium intake and Fos-IR cells in caudate
      putamen and accumbens nucleus induced by ANG II i.c.v. (b) potentiated urinary
      sodium excretion and Fos-OT-IR in hypothalamus and (c) increased the inhibitory
      response in plasma renin activity, in response to ANG II i.c.v. Our results
      indicate a possible functional desensitisation of AT1-R in response to ANG II,
      induced by repeated amphetamine exposure. This functional AT1-R desensitisation
      allows to unmask the effects of ANG II i.c.v. mediated by oxytocin. We conclude
      that the long lasting changes in brain AT1-R functionality should be considered
      among the psychostimulant-induced neuroadaptations.

PMID- 26299339
TI  - Rac1 contributes to cerebral ischemia reperfusion-induced injury in mice by
      regulation of Notch2.
AB  - BACKGROUND: Cerebral ischemia-reperfusion (IR) injury is a complex pathological
      process that can cause irreversible brain damage, neuronal injury or death from
      brain ischemia. Rac1 GTPase is involved in cellular protection from IR injury.
      However, the mechanism of protection and the molecules affected by Rac1 remain to
      be defined. METHODS AND RESULTS: C57BL/6 mice were subjected to middle cerebral
      artery occlusion for 1h, followed by 24-h reperfusion. In this in vivo model of
      cerebral IR injury, mice treated with the Rac GTPase inhibitor NSC23766 or Rac1
      small interfering RNA (siRNA) had better short-term (72 h) neurologic scores,
      less infarction volume, higher production of antioxidant enzymes, lower lipid
      peroxide, and reduced apoptosis compared with a vehicle-treated group or a
      control-siRNA group. However, long-term (14 day) neurologic scores were worse for
      the two treatments compared to controls. Microarray and quantitative polymerase
      chain reaction (PCR) revealed that Notch2 was downregulated under NSC23766
      treatment. Notch2 protein levels decreased with NSC23766 and Rac1 siRNA in vitro
      and in vivo. Cell survival increased with the Notch signaling inhibitor DAPT or
      Notch2 siRNA and NICD2 attenuated the NSC23766 effect. In addition,
      immunoblotting showed that DAPT and Notch2 siRNA changed the levels of apoptosis
      regulating proteins. NFkB mediated Rac1, which regulated Notch2 in an oxygen
      glucose deprivation model. Both inhibitors of Notch2 and Rac1 enhanced neural
      stem cell differentiation. CONCLUSIONS: This study demonstrated the importance of
      Rac1 regulation of Notch2 in mediating cerebral IR-induced production of
      injurious reactive oxygen species and cell death in vitro and in vivo in the
      short term. Targeted inhibition of Rac1 or Notch2 is new avenue for in vivo
      therapy aimed at protecting organs at risk from IR injury.

PMID- 26299340
TI  - P2X7 receptor activation downmodulates Na(+)-dependent high-affinity GABA and
      glutamate transport into rat brain cortex synaptosomes.
AB  - Sodium-dependent high-affinity amino-acid transporters play crucial roles in
      terminating synaptic transmission in the central nervous system (CNS). However,
      there is lack of information about the mechanisms underlying the regulation of
      amino-acid transport by fast-acting neuromodulators, like ATP. Here, we
      investigated whether activation of the ATP-sensitive P2X7 receptor modulates
      Na(+)-dependent high-affinity gamma-aminobutyric acid (GABA) and glutamate uptake
      into nerve terminals (synaptosomes) of the rat cerebral cortex. Radiolabeled
      neurotransmitter accumulation was evaluated by liquid scintillation spectrometry.
      The cell-permeant sodium-selective fluorescent indicator, SBFI-AM, was used to
      estimate Na(+) influx across plasma membrane. 2'(3')-O-(4-benzoylbenzoyl)ATP
      (BzATP, 3-300 MUM), a prototypic P2X7 receptor agonist, concentration-dependently
      decreased [(3)H]GABA (14%) and [(14)C]glutamate (24%) uptake; BzATP decreased
      transport maximum velocity (Vmax) without affecting the Michaelis constant (Km)
      values. The selective P2X7 receptor antagonist, A-438079 (3 MUM), prevented
      inhibition of [(3)H]GABA and [(14)C]glutamate uptake by BzATP (100 MUM). The
      inhibitory effect of BzATP coincided with its ability to increase intracellular
      Na(+) and was mimicked by Na(+) ionophores, like gramicidin and monensin.
      Increases in intracellular Na(+) (with veratridine or ouabain) or substitution of
      extracellular Na(+) by N-methyl-D-glucamine (NMDG)(+) all decreased [(3)H]GABA
      and [(14)C]glutamate uptake and attenuated BzATP effects. Uptake inhibition by
      BzATP (100 MUM) was also attenuated by calmidazolium, which selectively inhibits
      Na(+) currents through the P2X7 receptor pore. In conclusion, disruption of the
      Na(+) gradient by P2X7 receptor activation downmodulates high-affinity GABA and
      glutamate uptake into rat cortical synaptosomes. Interference with amino-acid
      transport efficacy may constitute a novel target for therapeutic management of
      cortical excitability.

PMID- 26299342
TI  - Encapsulation and subsequent freeze-drying of Lactobacillus reuteri CRL 1324 for
      its potential inclusion in vaginal probiotic formulations.
AB  - Probiotic formulations must include a high number of viable and active
      microorganisms. In this work, the survival of human vaginal Lactobacillus reuteri
      CRL 1324 during encapsulation, lyophilization and storage, and the activity of
      encapsulated and/or freeze-dried bacterial cells were evaluated. Extrusion-ionic
      gelation technique was applied to encapsulate L. reuteri CRL 1324, using xanthan
      and gellan. Encapsulated and free bacterial cells were freeze-dried with or
      without lactose and skim milk as lyoprotectors. The different systems obtained
      were stored at room temperature and at 4 degrees C for 150days. The following
      determinations were performed: L. reuteri CRL 1324 viability, microorganism
      released from capsules, survival in a medium simulating the vaginal fluid and
      maintenance of beneficial properties (growth inhibition of opportunistic
      pathogenic Streptococcus agalactiae NH 17 and biofilm formation). L. reuteri CRL
      1324 encapsulation was efficient, allowing the recovery of a high number of
      entrapped lactobacilli. The survival of encapsulated L. reuteri during
      lyophilization and storage was significantly higher in the presence of
      lyoprotectors. At the end of storage, the highest numbers of viable cells were
      obtained in free or encapsulated cells freeze-dried with lyoprotectors, stored at
      4 degrees C. Encapsulated and/or lyophilized L. reuteri cells maintained their
      viability in simulated vaginal fluid as well as the ability to inhibit S.
      agalactiae NH 17 growth and to form biofilm. Encapsulated and freeze-dried L.
      reuteri CRL 1324 can be included in a suitable pharmaceutical form for vaginal
      application to prevent or treat urogenital infections in women. 

PMID- 26299341
TI  - RNF4 negatively regulates NF-kappaB signaling by down-regulating TAB2.
AB  - Most of NF-kappaB (nuclear factor kappa B) signaling molecules have various types
      of post-translational modifications. In this study, we focused on ubiquitination
      and designed a siRNA library including most ubiquitin-binding domains. With this
      library, we identified several candidate regulators of canonical NF-kappaB
      pathway, including RNF4. Overexpression of RNF4 impaired NF-kappaB activation in
      a dose-dependent manner, whereas RNF4 knockdown potentiated NF-kappaB activation.
      We showed that RNF4 interacts with the TAK1-TAB2-TAB3 complex, but not TAB1.
      Further, we found that RNF4 specifically down-regulated TAB2 through a lysosomal
      pathway, and knockdown of RNF4 impaired endogenous TAB2 degradation. Therefore,
      our findings will provide new insights into the negative regulation of NF-kappaB
      signaling. 

PMID- 26299344
TI  - Epilepsy classification and additional definitions in occipital lobe epilepsy.
AB  - AIM: To evaluate epileptic children with occipital lobe epilepsy (OLE) in the
      light of the characteristics of Panayiotopoulos syndrome and late-onset occipital
      lobe epilepsy of Gastaut (OLE-G). METHODS: Patients were categorized into six
      groups: primary OLE with autonomic symptoms (Panayiotopoulos syndrome), primary
      OLE with visual symptoms (OLE-G), secondary OLE with autonomic symptoms (P-type
      sOLE), secondary OLE with visual symptoms (G-type sOLE), and non-categorized
      primary OLE and non-categorized secondary OLE according to characteristic ictal
      symptoms of both Panayiotopoulos syndrome and OLE-G, as well as aetiology
      (primary or secondary). Patients were compared with regards to seizure symptoms,
      aetiology, cranial imaging, EEG, treatment and outcome. RESULTS: Of 108 patients
      with OLE (6.4+/-3.9 years of age), 60 patients constituted primary groups (32
      with Panayiotopoulos syndrome, 11 with OLE-G, and 17 with non-categorized primary
      OLE); the other 48 patients constituted secondary groups (eight with P-type sOLE,
      three with G-type sOLE, and 37 with non-categorized sOLE). Epileptiform activity
      was restricted to the occipital area in half of the patients. Generalized
      epileptiform activity was observed in three patients, including a patient with
      Panayiotopoulos syndrome (PS). Only one patient had refractory epilepsy in the
      primary groups while such patients made up 29% in the secondary groups.
      CONCLUSION: In OLE, typical autonomic or visual ictal symptoms of Panayiotopoulos
      syndrome and OLE-G do not necessarily indicate primary (i.e. genetic or
      idiopathic) aetiology. Moreover, primary OLE may not present with these symptoms.
      Since there are many patients with OLE who do not exhibit the characteristics of
      Panayiotopoulos syndrome or OLE-G, additional definitions and terminology appear
      to be necessary to differentiate between such patients in both clinical practice
      and studies.

PMID- 26299343
TI  - Investigation of Hexadecylphosphocholine (miltefosine) usage in Pegylated
      liposomal doxorubicin as a synergistic ingredient: In vitro and in vivo
      evaluation in mice bearing C26 colon carcinoma and B16F0 melanoma.
AB  - In this investigation, Hexadecylphosphocholine (HePC, miltefosine) was being used
      as a new ingredient in Pegylated liposomal doxorubicin (PLD) and different
      aspects of this integration such as its effect on doxorubicin (Dox) release and
      cell uptake, cytotoxicity of liposomes, in vivo distribution and half-life
      clearance time of Dox as well as median survival time were illustrated. The
      liposomal formulations were Pegylated liposomal doxorubicin containing 0, 0.5, 1,
      2 and 4% mole ratios of HePC (HePC-PLD) and their respective Dox-free liposomes
      (HePC-PLs). The cells used were colon carcinoma (C26), adriamycin-resistant
      breast cancer (MCF-7-ADR), and B16F0 melanoma cell lines, of which C26 and B16F0
      cells were exploited for tumoring in BALB/c and C57Bl/6 mice, respectively. In
      most cases, increase in miltefosine percentage resulted in physically liposomal
      instability, increased Dox delivery and toxicity and reduced blood half-life of
      Dox. Overall, HePC 4% -PLD and PLD differed significantly in many respects and it
      was considered too toxic to be injected at the same dose (15mg Dox/ kg) as PLD.
      Although HePC 2% -PLD could extend the median survival time marginally in
      comparison to PLD, the concept of HePC- containing liposomes merits further
      investigation. 

PMID- 26299345
TI  - Solid-phase synthesis of 5'-triantennary N-acetylgalactosamine conjugated
      antisense oligonucleotides using phosphoramidite chemistry.
AB  - A convenient solid-phase synthetic method was developed for assembling a
      triantennary N-acetylgalactosamine (GalNAc) cluster on the 5'-end of antisense
      oligonucleotide using phosphoramidite chemistry. Conjugation of the 5'
      triantennary GalNAc cluster improved potency of the 14 mer ASO 7-fold in mice and
      more than 50 fold in hepatocytes. The synthetic approach described in this Letter
      simplifies the synthesis of 5'-triantennary GalNAc cluster conjugated ASOs and
      helps understand the structure-activity relationship for targeting hepatocytes
      with oligonucleotide therapeutics. 

PMID- 26299346
TI  - Design and synthesis of 11alpha-substituted bile acid derivatives as potential
      anti-tuberculosis agents.
AB  - We have synthesized a series of novel 11alpha-triazoyl bile acid derivatives. In
      addition, we also have synthesized N-alkyl and N-acyl derivatives of C-11 amino
      bile acid esters. All the compounds were evaluated for the inhibitory activity
      against Mycobacterium tuberculosis H37Ra (MTB) at 30 MUg/mL level. Four lead
      compounds (2b, 3, 7 and 8) were further confirmed from their dose dependent
      effect against MTB. These compounds were found to be active against Dormant and
      active stage MTB under both in vitro as well as within THP1 host macrophages. The
      most promising compound 2b showed strong antitubercular activities against MTB
      under in vitro and ex vivo (IC90 value of ~3 MUg/mL) conditions and almost
      insignificant cytotoxicity up to 100 MUg/mL against THP-1, A549 and PANC-1 human
      cancer cell lines. Inactivity of all these compounds against Gram positive and
      Gram negative bacteria indicates their specificity. Molecular docking studies of
      these compounds into the active site of DprE1 enzyme revealed a similar binding
      mode to native ligands in the crystal structure thereby helping to establish a
      structural basis of inhibition of MTB. The synthesized compounds were analyzed
      for ADME properties and showed potential to develop good oral drug candidates.
      Our results clearly indicate the identification of some novel, selective and
      specific inhibitors against MTB that can be explored further for potential
      antitubercular drug.

PMID- 26299347
TI  - Optimization of a small molecule probe that restores e-cadherin expression.
AB  - E-cadherin is a ubiquitous trans-membrane protein that has important functions in
      cellular contacts and has been shown to play a role in the epithelial mesenchymal
      transition. We have previously reported the use of an HTS screen to identify
      compounds that are capable of restoring e-cadherin in cancer cells. Here, we
      report the additional medicinal chemistry optimization of these molecules,
      resulting in new molecules that restore e-cadherin expression at low micromolar
      concentrations. Further, we report preliminary pharmacokinetic data on a
      compound, ML327, that can be used as a probe of e-cadherin restoration. 

PMID- 26299348
TI  - Synthesis, structure-activity relationship and biological evaluation of novel
      nitrogen mustard sophoridinic acid derivatives as potential anticancer agents.
AB  - A series of novel nitrogen mustard sophoridinic acid derivatives were designed,
      synthesized and evaluated for their cytotoxicity. Of the newly synthesized
      compounds, compound 6 exhibited a potent effect against hepatocellular carcinoma
      in vitro and in vivo. SAR analysis indicated that introduction of a nitrogen
      mustard group to the structure of sophoridinic acid significantly enhance the
      antitumor activity. Moreover, molecular docking study exhibited benzyl group
      introduced to the nitrogen atom at the 12-position and aryl nitrogen mustard
      group at the 4'-carboxyl region for compound 6 were beneficial for the higher
      anticancer activity. This work provides useful information for further structural
      modifications of these compounds and for the synthesis of new, potent antitumor
      agents.

PMID- 26299349
TI  - Design and synthesis of N-[6-(Substituted Aminoethylideneamino)-2-Hydroxyindan-1
      yl]arylamides as selective and potent muscarinic M1 agonists.
AB  - The observation that cholinergic deafferentation of circuits projecting from
      forebrain basal nuclei to frontal and hippocampal circuits occurs in Alzheimer's
      disease has led to drug-targeting of muscarinic M1 receptors to alleviate
      cognitive symptoms. The high homology within the acetylcholine binding domain of
      this family however has made receptor-selective ligand development challenging.
      This work presents the synthesis scheme, pharmacokinetic and structure-activity
      relationship study findings for M1-selective ligand, LY593093. Pharmacologically
      the compound acts as an orthosteric ligand. The homology modeling work presented
      however will illustrate that compound binding spans from the acetylcholine pocket
      to the extracellular loops of the receptor, a common allosteric vestibule for the
      muscarinic protein family. Altogether LY593093 represents a growing class of
      multi-topic ligands which interact with the receptors in both the ortho- and
      allosteric binding sites, but which exert their activation mechanism as an
      orthosteric ligand. 

PMID- 26299350
TI  - Discovery, synthesis and biochemical profiling of purine-2,6-dione derivatives as
      inhibitors of the human poly(A)-selective ribonuclease Caf1.
AB  - Eukaryotic mRNA contains a 3' poly(A) tail, which plays important roles in the
      regulation of mRNA stability and translation. Well-characterized enzymes involved
      in the shortening of the poly(A) tail include the multi-subunit Ccr4-Not
      deadenylase, which contains the Caf1 (Pop2) and Ccr4 catalytic components, and
      poly(A)-specific ribonuclease (PARN). Two Mg(2+) ions present in the active sites
      of these ribonucleases are required for RNA cleavage. Here, we report the
      discovery, synthesis and biochemical profiling of purine-2,6-dione derivatives as
      (sub)micromolar inhibitors of Caf1. 

PMID- 26299352
TI  - The heavy atom effect on Zn(ii) phthalocyanine derivatives: a theoretical
      exploration of the photophysical properties.
AB  - Absorption electronic spectra, singlet-triplet energy gaps and spin-orbit matrix
      elements have been computed at DFT and TDDFT levels of theory for a series of
      substituted Zn(ii)-phthalocyanines (ZnPcs), recently proposed as potential
      photosensitizers in photodynamic therapy (PDT). Their photophysical properties
      have been rationalized in the light of the substitution pattern which includes
      the position, the donor or withdrawing nature, and the relative donating force of
      peripheral and non-peripheral ligands. Moreover, the effects of heavy
      substituents on these properties have been investigated by introducing a
      different number of iodine atoms on the phthalocyanine macrocycle. The results
      show that the substitution pattern significantly affects the absorption spectra,
      but just slightly modifies the DeltaES-T values. The presence of heavy atoms
      produces a significant effect on the photophysical properties of the investigated
      compounds enhancing the spin-orbit coupling (SOC) values. 

PMID- 26299351
TI  - High prevalence and antimicrobial resistance of urinary tract infection isolates
      in febrile young children without localizing signs in Taiwan.
AB  - BACKGROUND: Antimicrobial susceptibility and prevalence of pediatric urinary
      tract infection (UTI) is very useful for pediatricians in selecting effective
      antibiotics in time to improve outcomes in patients. This study aimed to
      determine the prevalence rate, bacterial distribution, and antimicrobial
      susceptibility of UTI in febrile young children at a teaching hospital in
      northern Taiwan. METHODS: From January 2011 to December 2011, all urinary
      isolates from suspected cases of UTI in febrile young children aged from 1 day to
      36 months visiting the Pediatric Emergency Room of Chang Gung Children's
      Hospital, Taoyuan, Taiwan were identified by conventional methods. Antibiotic
      susceptibility was determined according to the Clinical and Laboratory Standards
      Institute. RESULTS: A total of 5470 (78%) from 7009 eligible children were
      enrolled in the study, and 619 (11.3%) had a diagnosis of UTI. The most prevalent
      bacterium was Escherichia coli (68%) followed by Klebsiella pneumoniae (8.1%) and
      Proteus mirabilis (6.8%). Ampicillin, piperacillin, and trimethoprim
      sulfamethoxazole (TMP-SMX) showed a higher resistance rate in the three
      predominant bacteria. All tested bacteria showed higher resistance to ampicillin
      (79.3%) and TMP-SMX (44.1%), and lower resistance to cefazolin (17.7%) and
      gentamicin (13.0%). Fourteen percent of the isolates produced extended spectrum
      beta-lactamase (ESBL), among which 93.33% were E. coli isolates. CONCLUSION: The
      overall prevalence of UTI in this study was higher than previously reported in
      febrile children. Higher antimicrobial resistance was found in ampicillin and TMP
      SMX. Among commonly used antibiotics, cefazolin and gentamicin are recommended to
      treat UTI in febrile children aged < 3 years without localizing signs.

PMID- 26299353
TI  - Impact of variations in fatty liver on sonographic detection of focal hepatic
      lesions originally identified by CT.
AB  - PURPOSE: The aim of this study was to investigate the influence of variations in
      fatty liver on the ultrasonographic detection of focal liver lesions. METHODS: A
      total of 229 patients with varying degrees of fatty liver and focal liver lesions
      and 200 patients with focal liver lesions but no fatty liver were randomly
      selected for inclusion in groups I and II, respectively. Findings of focal liver
      lesions identified on computed tomography were taken as the reference, and
      findings on ultrasonography were compared with them. RESULTS: The number of focal
      liver lesions in groups I and II were 501 and 413, respectively. The
      ultrasonographic detection rates of focal liver lesions in groups I and II were
      86.8% (435/501) and 94.2% (389/413), respectively. Comparison of the detection of
      the focal lesions between patients with and without fatty liver or different
      grades of fatty liver were as follows: mild fatty liver (162/177) vs. liver
      without fat infiltration (389/413) (P=0.277); mild fatty liver (162/177) vs.
      moderate fatty liver (190/212) (P=0.604); mild fatty liver (162/177) vs. severe
      fatty liver (83/112) (P<0.001); moderate fatty liver (190/212) vs. liver without
      fat infiltration (389/413) (P=0.051); moderate fatty liver (190/212) vs. severe
      fatty liver (83/112) (P<0.001); severe fatty liver (83/112) vs. liver without fat
      infiltration (389/413) (P<0.001); and fatty liver (435/501) vs. liver without fat
      infiltration (389/413) (P<0.001). CONCLUSION: Mild and moderate fatty liver are
      not significantly associated with the visualization of the lesion, while severe
      fatty liver usually impairs the detection of focal lesions in the liver. If a
      patient with severe fatty liver is suspected to have a liver tumor,
      ultrasonography should only be chosen cautiously in case of a missed diagnosis.

PMID- 26299354
TI  - The follicular variant of papillary thyroid carcinoma: characteristics of
      preoperative ultrasonography and cytology.
AB  - PURPOSE: The goal of this study was to validate the ultrasonography (US) and
      cytopathological features that are used in the diagnosis of the follicular
      variant of papillary thyroid carcinoma (FVPTC) and to characterize the role of
      BRAF (V600E) mutation analysis in the diagnosis of FVPTC. METHODS: From May 2012
      to February 2014, 40 thyroid nodules from 40 patients (mean age, 56.2 years;
      range, 26 to 81 years) diagnosed with FVPTC were included in this study. The US
      features of the nodules were analyzed and the nodules were classified as probably
      benign or suspicious for malignancy. Twenty-three thyroid nodules (57.5%)
      underwent BRAF (V600E) mutation analysis. Clinical information and
      histopathologic results were obtained by reviewing the medical records of the
      patients. RESULTS: Thirty nodules (75.0%) were classified as suspicious for
      malignancy, while 10 (25.0%) were classified as probably benign. Seven of the
      eight nodules (87.5%) with atypia of undetermined significance/follicular lesion
      of undetermined significance (AUS/FLUS) cytology showed suspicious US features,
      while one of the two nodules (50.0%) with follicular neoplasm cytology presented
      suspicious US features. Five of the 23 nodules (21.7%) that underwent BRAF
      (V600E) mutation analysis had positive results, all of which were diagnosed as
      suspicious for malignancy or malignant based on cytology. None of the nodules
      with benign, AUS/FLUS, or follicular neoplasm cytology were positive for the BRAF
      (V600E) mutation. CONCLUSION: US features allow nodules to be classified as
      suspicious for malignancy, and the presence of suspicious US features in nodules
      with ambiguous cytology may aid in the diagnosis of FVPTC. BRAF (V600E) mutation
      analysis is of limited value in the diagnosis of FVPTC.

PMID- 26299355
TI  - Reduction of dichloro(diaza-phospha)stibanes - isolation of a donor-stabilized
      distibenium dication.
AB  - A reaction of antimonytrichloride SbCl3 with potassium
      bis(terphenylimino)phosphide K[(TerN)2P] smoothly afforded a novel class of mixed
      diazadipnictanes, namely dichloro(diaza-phospha)stibane
      [Ter2N2P((III))Sb((III))Cl2], which is considered to exist as open chain-like and
      cyclic isomers in an equilibrium. [Ter2N2PSbCl2] is a versatile starting material
      for reduction and halide abstraction experiments. Halide abstraction led to the
      formation of a cyclic diazastibaphosphenium cation [P(MU-NTer)2SbCl](+). Upon
      reduction of [Ter2N2PSbCl2], the transient existence of the novel mixed
      biradicaloid [P(MU-NTer)2Sb] was proven by a trapping experiment with an alkyne,
      while reduction in the absence of trapping agents afforded the eight-membered
      heterocycle [Sb2-{MU-(TerN)2P}2]. This constitutional isomer of a dimerized
      biradicaloid features a bonding situation that indicates the presence of a donor
      stabilized [Sb2](2+) ion. 

PMID- 26299357
TI  - Solvent-induced reversible solid-state colour change of an intramolecular charge
      transfer complex.
AB  - A dynamic intramolecular charge-transfer (CT) complex was designed that displayed
      reversible colour changes in the solid-state when treated with different organic
      solvents. The origins of the dichromatism were shown to be due to solvent
      inclusion, which induced changes in the relative orientations of the donor pyrene
      and acceptor naphthalenediimide units. 

PMID- 26299356
TI  - Upregulation of the gene expression of CLOCK is correlated with hypoxia-inducible
      factor 1alpha in advanced varicose lesions.
AB  - According to previous literature, venous hypoxia and the hypoxia-inducible factor
      (HIF) pathway may contribute to the pathogenesis of varicose veins (VVs). It is
      widely accepted that the circadian locomotor output cycles kaput (CLOCK) gene
      affects nucleotide excision repair, DNA damage checkpoints and apoptosis in
      mammalian organisms; however, the expression levels of CLOCK in varicose veins
      remain to be elucidated. The aim of the present study was to detect the
      expression of the circadian clock gene in initial and advanced varicose lesions
      and analyze the correlation between the CLOCK gene, HIF-1alpha, and its target
      gene, vascular endothelial growth factor (VEGF), in VVs. Sections of the great
      saphenous veins (GSVs) were obtained from patients undergoing ligation and
      stripping for VVs (n=70) and a control group undergoing coronary artery bypass
      grafting with GSV harvest (n=11). All VV patients had incompetent GSVs, according
      to color flow duplex scanning. C-class VVs were determined according to the
      clinical-etiology-anatomy-pathophysiology classification for venous diseases
      following physical examination of the patients with VV. Reverse transcription
      quantitative polymerase chain reaction was used to determine the expression
      levels of the CLOCK gene, HIF-1alpha and VEGF. Immunohistochemical analysis was
      also performed. The patients with VVs were divided into those with initial
      varicose lesions (C3 and C4) and advanced varicose lesions (C5 and C6). In total,
      21 of the patients had C3 lesions, 23 had C4 lesions, 14 had C5 lesions and 12
      had C6 chronic venous disease. The expression of the CLOCK gene was significantly
      higher in the VV lesions of the GSV, compared with the normal GSVs (P<0.0001).
      The same trend was found in the expression levels of HIF-1alpha and its target
      gene, VEGF, in the VV lesions (P=0.003 and P<0.0001, respectively). Subgroup
      analysis revealed that the expression levels of the CLOCK gene, HIF-1alpha and
      VEGF were significantly higher in the advanced stage varicose lesions, compared
      with the initial varicose lesions (P<0.0001, P=0.0014 and P<0.0001,
      respectively). However, no statistically significant difference was identified in
      the expression levels of the aforementioned genes in the C3 and C4 lesions. The
      results demonstrated that the expression gene levels of CLOCK, HIF-1alpha and its
      target gene, VEGF, increased significantly in advanced stage varicose lesions.
      Therefore, upregulation of the CLOCK gene in the vessel walls of veins may be
      involved in the pathogenesis of VVs and the progression of venous disease.

PMID- 26299358
TI  - Phil Bryden: Husband, father, colleague, friend.
AB  - This article describes some of the personal life of M. Philip Bryden, and how it
      interacted with his professional and scholarly achievements.

PMID- 26299359
TI  - Growth of colloidal PbS nanosheets and the enhancement of their
      photoluminescence.
AB  - Dual photoluminescence peaks observed during the synthesis of colloidal PbS
      nanosheets reveal their growth mechanism - two-dimensional attachments of the
      quantum dots. Well-grown nanosheets show the photoluminescence linewidth of 95
      meV at room temperature. Aged nanosheets in toluene have enhanced
      photoluminescence with intensity improved by an order of magnitude. 

PMID- 26299361
TI  - A Symmetrical Quasi-Classical Spin-Mapping Model for the Electronic Degrees of
      Freedom in Non-Adiabatic Processes.
AB  - A recent series of papers has shown that a symmetrical quasi-classical (SQC)
      windowing procedure applied to the Meyer-Miller (MM) classical vibronic
      Hamiltonian provides a very good treatment of electronically nonadiabatic
      processes in a variety of benchmark model systems, including systems that exhibit
      strong quantum coherence effects and some which other approximate approaches have
      difficulty in describing correctly. In this paper, a different classical
      electronic Hamiltonian for the treatment of electronically nonadiabatic processes
      is proposed (and "quantized" via the SQC windowing approach), which maps the
      dynamics of F coupled electronic states to a set of F spin-(1)/2 degrees of
      freedom (DOF), similar to the Fermionic spin model described by Miller and White
      (J. Chem. Phys. 1986, 84, 5059). It is noted that this spin-mapping (SM)
      Hamiltonian is an exact Hamiltonian if treated as a quantum mechanical (QM)
      operator-and thus QM'ly equivalent to the MM Hamiltonian-but that an analytically
      distinct classical analogue is obtained by replacing the QM spin-operators with
      their classical counterparts. Due to their analytic differences, a practical
      comparison is then made between the MM and SM Hamiltonians (when quantized with
      the SQC technique) by applying the latter to many of the same benchmark test
      problems successfully treated in our recent work with the SQC/MM model. We find
      that for every benchmark problem the MM model provides (slightly) better
      agreement with the correct quantum nonadiabatic transition probabilities than
      does the new SM model. This is despite the fact that one might expect, a priori,
      a more natural description of electronic state populations (occupied versus
      unoccupied) to be provided by DOF with only two states, i.e., spin-(1)/2 DOF,
      rather than by harmonic oscillator DOF which have an infinite manifold of states
      (though only two of these are ever occupied). 

PMID- 26299360
TI  - Efficient Optical Energy Harvesting in Self-Accelerating Beams.
AB  - We report the experimental observation of energetically confined self
      accelerating optical beams propagating along various convex trajectories. We show
      that, under an appropriate transverse compression of their spatial spectra, these
      self-accelerating beams can exhibit a dramatic enhancement of their peak
      intensity and a significant decrease of their transverse expansion, yet retaining
      both the expected acceleration profile and the intrinsic self-healing properties.
      We found our experimental results to be in excellent agreement with the numerical
      simulations. We expect further applications in such contexts where power budget
      and optimal spatial confinement can be important limiting factors. 

PMID- 26299362
TI  - The role of psychological well-being in obese and overweight older adults.
AB  - Being obese or overweight is often associated with impaired quality of life and
      psychological well-being (PWB) in comparison with normal-weight people (Giuli et
      al., 2014), both in developed and developing countries. PWB is considered a very
      important correlate of subjective well-being in people with excess weight. The
      concept of PWB is based on Ryff's multidimensional model (Ryff, 2014), which
      considers well-being as eudaemonic concept, and includes six dimensions:
      autonomy, environmental mastery, personal growth, positive relations with others,
      purpose in life, and self-acceptance. Few studies have analyzed the role of
      specific correlates of perceived well-being in the obese and overweight Italian
      older population. The purpose of this study was to evaluate the role of perceived
      well-being in obese and overweight older adults. Our study included 124
      overweight and obese older participants, aged 60 years or more, selected from
      patients attending the Division of Endocrinology, Department of Clinical and
      Molecular Sciences of Polytechnic University of Marche (Italy). As previously
      described (Giuli et al., 2014), the participants were recruited on the basis of
      specific inclusion/exclusion criteria, in a period of three years (January 2010
      December 2012). 

PMID- 26299363
TI  - Isolation and molecular characterization of Toxoplasma gondii in a colony of
      captive black-capped squirrel monkeys (Saimiri boliviensis).
AB  - Toxoplasmosis is commonly asymptomatic; however, it can be a fatal multisystemic
      disease in some animal species, such as New World monkeys. An outbreak of acute
      fatal toxoplasmosis was reported in a colony of black-capped squirrel monkeys
      (Saimiri boliviensis) from the zoo of La Plata, Argentina. Post-mortem
      examination of two monkeys revealed macroscopical and microscopical lesions
      compatible with acute toxoplasmosis. The presence of Toxoplasma gondii was
      confirmed by immunohistochemistry on monkey tissues, bioassay in mice and PCR
      using the specific primers B22-B23. By PCR-RFLP analysis, T. gondii isolated in
      mice, deriving from both monkeys, showed the same restriction pattern, with most
      markers showing a type III restriction pattern, except for C22-8 (type II) and
      C29-2 (type I). To our knowledge this is the first report of fatal toxoplasmosis
      in S. boliviensis caused by a non-canonical or atypical genotype of T. gondii. 

PMID- 26299364
TI  - Heterozygous Loss-of-Function Mutations in DLL4 Cause Adams-Oliver Syndrome.
AB  - Adams-Oliver syndrome (AOS) is a rare developmental disorder characterized by the
      presence of aplasia cutis congenita (ACC) of the scalp vertex and terminal limb
      reduction defects. Cardiovascular anomalies are also frequently observed.
      Mutations in five genes have been identified as a cause for AOS prior to this
      report. Mutations in EOGT and DOCK6 cause autosomal-recessive AOS, whereas
      mutations in ARHGAP31, RBPJ, and NOTCH1 lead to autosomal-dominant AOS. Because
      RBPJ, NOTCH1, and EOGT are involved in NOTCH signaling, we hypothesized that
      mutations in other genes involved in this pathway might also be implicated in AOS
      pathogenesis. Using a candidate-gene-based approach, we prioritized DLL4, a
      critical NOTCH ligand, due to its essential role in vascular development in the
      context of cardiovascular features in AOS-affected individuals. Targeted
      resequencing of the DLL4 gene with a custom enrichment panel in 89 independent
      families resulted in the identification of seven mutations. A defect in DLL4 was
      also detected in two families via whole-exome or genome sequencing. In total,
      nine heterozygous mutations in DLL4 were identified, including two nonsense and
      seven missense variants, the latter encompassing four mutations that replace or
      create cysteine residues, which are most likely critical for maintaining
      structural integrity of the protein. Affected individuals with DLL4 mutations
      present with variable clinical expression with no emerging genotype-phenotype
      correlations. Our findings demonstrate that DLL4 mutations are an additional
      cause of autosomal-dominant AOS or isolated ACC and provide further evidence for
      a key role of NOTCH signaling in the etiology of this disorder. 

PMID- 26299365
TI  - Accurate Non-parametric Estimation of Recent Effective Population Size from
      Segments of Identity by Descent.
AB  - Existing methods for estimating historical effective population size from genetic
      data have been unable to accurately estimate effective population size during the
      most recent past. We present a non-parametric method for accurately estimating
      recent effective population size by using inferred long segments of identity by
      descent (IBD). We found that inferred segments of IBD contain information about
      effective population size from around 4 generations to around 50 generations ago
      for SNP array data and to over 200 generations ago for sequence data. In human
      populations that we examined, the estimates of effective size were approximately
      one-third of the census size. We estimate the effective population size of
      European-ancestry individuals in the UK four generations ago to be eight million
      and the effective population size of Finland four generations ago to be 0.7
      million. Our method is implemented in the open-source IBDNe software package. 

PMID- 26299367
TI  - Targeting the Wnt-Regulatory Protein CTNNBIP1 by microRNA-214 Enhances the
      Stemness and Self-Renewal of Cancer Stem-Like Cells in Lung Adenocarcinomas.
AB  - A novel hypothesis in cancer biology proposes that cancer growth is driven by
      cancer stem-like cells (CSLCs), also called tumor-initiating cells, which can
      self-renew and differentiate into multilineage progeny in a fashion similar to
      stem cells. However, the impact and underlying mechanisms of this process in lung
      adenocarcinoma (LAC) remain to be elucidated. Here, we report that microRNA-214
      (miR-214) contributes to cell self-renewal by directly targeting catenin beta
      interacting protein 1 (CTNNBIP1), a member of the Wnt signaling pathway. We
      demonstrate that miR-214 overexpression enhances stem-like properties in LAC
      cells and that miR-214 shows increased expression in CSLCs derived from primary
      tumor tissue and from two LAC cell lines (A549 and NCI-H1650). Strikingly,
      downregulation of miR-214 expression in CSLCs resulted in a significant decrease
      in spheroid formation and the expression of the stem-cell markers Nanog, Oct-4,
      and Sox-2. Finally, CTNNBIP1 was identified as a target of miR-214. miR-214
      expression in LAC was negatively correlated with CTNNBIP1 expression and
      positively correlated with differentiated cellular states. Moreover, CTNNBIP1
      expression correlated with longer overall survival in LAC patients. This study
      reveals that miR-214 plays a critical role in CSLC self-renewal and stemness by
      targeting CTNNBIP1. The identification of this functional miR-214-CTNNBIP1
      interaction that regulates self-renewal in CSLCs has the potential to direct the
      development of novel therapeutic strategies for LAC.

PMID- 26299366
TI  - Mutations in SPATA5 Are Associated with Microcephaly, Intellectual Disability,
      Seizures, and Hearing Loss.
AB  - Using whole-exome sequencing, we have identified in ten families 14 individuals
      with microcephaly, developmental delay, intellectual disability, hypotonia,
      spasticity, seizures, sensorineural hearing loss, cortical visual impairment, and
      rare autosomal-recessive predicted pathogenic variants in spermatogenesis
      associated protein 5 (SPATA5). SPATA5 encodes a ubiquitously expressed member of
      the ATPase associated with diverse activities (AAA) protein family and is
      involved in mitochondrial morphogenesis during early spermatogenesis. It might
      also play a role in post-translational modification during cell differentiation
      in neuronal development. Mutations in SPATA5 might affect brain development and
      function, resulting in microcephaly, developmental delay, and intellectual
      disability. 

PMID- 26299369
TI  - Negenegen: Sweet talk, disrespect, and abuse among rural auxiliary midwives in
      Mali.
AB  - OBJECTIVE: the purpose of this study was to explore disrespect and abuse toward
      women in labor from the perspective of auxiliary midwives. DESIGN: this study
      uses a cross-sectional, descriptive mixed-methods design using surveys and
      interviews. SETTING: Koutiala, Mali. PARTICIPANTS: 67 mostly rural auxiliary
      midwives. INTERVENTIONS: this was a descriptive study and had no intervention
      component. The variables of interest were Malian auxiliary midwives' reports of
      caring and respectful, as well as abusive and disrespectful, behaviours towards
      childbearing women. FINDINGS: participants reported abusive and disrespectful
      behaviour toward women, particularly yelling, insulting, and displaying a hostile
      or aggressive attitude. However, auxiliary midwives also stressed the importance
      of making women feel welcome and comfortable, sweet-talking to them throughout
      labor, and providing quality care. IMPLICATIONS FOR TRAINING AND PRACTICE: we
      recommend a strengths-based approach to pre-service and continuing education to
      ensure that auxiliary midwives meet the basic competencies for midwives and
      appreciate both the impact of their abusive and disrespectful behaviours and the
      value of the respectful care they already provide.

PMID- 26299368
TI  - STAT1 deficiency redirects IFN signalling toward suppression of TLR response
      through a feedback activation of STAT3.
AB  - Interferons (IFNs) potentiate macrophage activation typically via a STAT1
      dependent pathway. Recent studies suggest a functioning of STAT1-independent
      pathway in the regulation of gene expression by IFN-gamma, thus pointing to the
      diversity in cellular responses to IFNs. Many functions of IFNs rely on cross
      regulation of the responses to exogenous inflammatory mediators such as TLR
      ligands. Here we investigated the contribution of STAT1-independent pathway to
      macrophage activation and its underlying mechanism in the context of combined
      stimulation of IFN and TLR. We found that TLR-induced production of inflammatory
      cytokines (TNF-alpha, IL-12) was not simply nullified but was significantly
      suppressed by signaling common to IFN-gamma and IFN-beta in STAT1-null
      macrophages. Such a shift in the suppression of TLR response correlated with a
      sustained STAT3 activation and attenuation of NF-kappaB signaling. Using a
      JAK2/STAT3 pathway inhibitor or STAT3-specific siRNA, blocking STAT3 in that
      context restored TNF-alpha production and NF-kappaB signaling, thus indicating a
      functional cross-regulation among STAT1, STAT3, and NF-kappaB. Our results
      suggest that STAT1 deficiency reprograms IFN signaling from priming toward
      suppression of TLR response via feedback regulation of STAT3, which may provide a
      new insight into the host defense response against microbial pathogens in a
      situation of STAT1 deficiency. 

PMID- 26299370
TI  - Validity and reliability of the Turkish version of the Optimality Index-US (OI
      US) to assess maternity care outcomes.
AB  - BACKGROUND: Although obstetrical interventions are used commonly in Turkey, there
      is no standardized evidence-based assessment tool to evaluate maternity care
      outcomes. The Optimality Index-US (OI-US) is an evidence-based tool that was
      developed for the purpose of measuring aggregate perinatal care processes and
      outcomes against an optimal or best possible standard. This index has been
      validated and used in Netherlands, USA and UK until now. OBJECTIVE: The objective
      of this study was to adapt the OI-US to assess maternity care outcomes in Turkey.
      DESIGN: Translation and back translation were used to develop the Optimality
      Index-Turkey (OI-TR) version. To evaluate the content validity of the OI-TR, an
      expert panel group (n=10) reviewed the items and evidence-based quality of the OI
      TR for application in Turkey. Following the content validity process, the OI-TR
      was used to assess 150 healthy and 150 high-risk pregnant women who gave birth at
      a high volume, urban maternity hospital in Turkey. The scores between the two
      groups were compared to assess the discriminant validity of the OI-TR. The
      percentage of agreement between two raters and the Kappa statistic were
      calculated to evaluate the reliability. FINDINGS: Content validity was
      established for the OI-TR by an expert group. Discriminant validity was confirmed
      by comparing the OI scores of healthy pregnant women (mean OI score=77.65%) and
      those of high-risk pregnant women (mean OI score=78.60%). The percentage of
      agreement between the two raters was 96.19, and inter-rater agreement was
      provided for each item in the OI-TR. CONCLUSION: OI-TR is a valid and reliable
      tool that can be used to assess maternity care outcomes in Turkey. The results of
      this study indicate that although the risk statuses of the women differed, the
      type of care they received was essentially the same, as measured by the OI-TR.
      Care was not individualised based on risk and for a majority of items was
      inconsistent with evidence based practice, which is not optimal. IMPLICATIONS FOR
      PRACTICE: Use of the OI-TR will help to provide a standardized way to assess
      maternity care process and outcomes of maternity care in Turkey which can inform
      future research aimed at improving maternity care outcomes.

PMID- 26299371
TI  - Sense of coherence and childbearing choices: A cross sectional survey.
AB  - BACKGROUND: as concern for increasing rates of caesarean section and
      interventions in childbirth in Western countries mounts, the utility of the risk
      approach (inherent in the biomedical model of maternity care) is called into
      question. The theory of salutogenesis offers an alternative as it focuses on the
      causes of health rather than the causes of illness. Sense of coherence (SOC), the
      cornerstone of salutogenic theory, is a predictive indicator of health. We
      hypothesised that there is a relationship between a woman's SOC and the
      childbirth choices she makes in pregnancy. METHODS: the study aims to investigate
      the relationship between SOC and women's pregnancy and anticipated labour
      choices. A cross sectional survey was conducted where eligible women completed a
      questionnaire that provided information on SOC scores, Edinburgh Postnatal
      Depression (EPDS) scores, Support Behaviour Inventory (SBI) scores, pregnancy
      choices and demographics. FINDINGS: 1074 pregnant women completed the study.
      Compared to women with low SOC, women with high SOC were older, were less likely
      to identify pregnancy conditions, had lower EPDS scores and higher SBI scores.
      SOC was not associated with women's pregnancy choices. CONCLUSION: this study
      relates SOC to physical and emotional health in pregnancy as women with high SOC
      were less likely to identify pregnancy conditions, had less depressive symptoms
      and perceived higher levels of support compared to women with low SOC.
      Interestingly, SOC was not associated with pregnancy choices known to increase
      normal birth rates. More research is required to explore the relationship between
      SOC and women's birthing outcomes.

PMID- 26299373
TI  - Chirality sensing with stereodynamic biphenolate zinc complexes.
AB  - Two bidentate ligands consisting of a fluxional polyarylacetylene framework with
      terminal phenol groups were synthesized. Reaction with diethylzinc gives
      stereodynamic complexes that undergo distinct asymmetric transformation of the
      first kind upon binding of chiral amines and amino alcohols. The substrate-to
      ligand chirality imprinting at the zinc coordination sphere results in
      characteristic circular dichroism signals that can be used for direct
      enantiomeric excess (ee) analysis. This chemosensing approach bears potential for
      high-throughput ee screening with small sample amounts and reduced solvent waste
      compared to traditional high-performance liquid chromatography methods.

PMID- 26299372
TI  - Rhizobial strains isolated from nodules of Medicago marina in southwest Spain are
      abiotic-stress tolerant and symbiotically diverse.
AB  - The isolation and characterisation of nitrogen-fixing root nodule bacteria from
      Medicago marina, a tolerant legume species, were studied in two areas from
      southwest Spain. A total of 30 out of 82 isolates with distinct ERIC-PCR
      fingerprints were analysed on the basis of molecular (PCR-RFLP of the 16S-23S
      rDNA intergenic spacer region (IGS) with two endonucleases, analysis of the 16S
      rDNA and symbiotic nodC gene sequences, plasmid profiles and SDS-PAGE of LPS,
      including the partial sequence of the housekeeping gene glnII and the symbiotic
      gene nodA of some representatives), physiological (utilisation of sole carbon
      sources, tolerance to antibiotics, NaCl, heavy metals, temperature and pH) and
      symbiotic parameters (efficacy on M. marina, M. minima, M. murex, M. orbicularis,
      M. polymorpha, M. sativa and M. truncatula). All the bacteria isolated from M.
      marina nodules belonged to Ensifer meliloti, except for one strain that belonged
      to E. medicae. To determine the nodulation range of M. marina, 10 different
      Ensifer species were tested for their ability to nodulate on this plant. E.
      kummerowiae CCBAU 71714 and the E. medicae control strain M19.1 were the only
      Ensifer species tested that developed nitrogen-fixing nodules on this plant. Most
      of the M. marina-nodulating strains showed tolerance to stress factors and all of
      them shared the presence of a gene similar to cadA, a gene that encodes for a PIB
      type ATPase, which is a transporter belonging to the large superfamily of ATP
      driven pumps involved in the transport of metals across cell membranes. 

PMID- 26299374
TI  - Historical introgression among the American live oaks and the comparative nature
      of tests for introgression.
AB  - Introgressive hybridization challenges the concepts we use to define species and
      infer phylogenetic relationships. Methods for inferring historical introgression
      from the genomes of extant species, such as ABBA-BABA tests, are widely used,
      however, their results can be easily misinterpreted. Because these tests are
      inherently comparative, they are sensitive to the effects of missing data
      (unsampled species) and nonindependence (hierarchical relationships among
      species). We demonstrate this using genomic RADseq data sampled from all extant
      species in the American live oaks (Quercus series Virentes), a group notorious
      for hybridization. By considering all species and their phylogenetic
      relationships, we were able to distinguish true hybridizing lineages from those
      that falsely appear admixed. Six of seven species show evidence of admixture,
      often with multiple other species, but which is explained by introgression among
      a few related lineages occurring in close proximity. We identify the Cuban oak as
      the most admixed lineage and test alternative scenarios for its origin. The live
      oaks form a continuous ring-like distribution around the Gulf of Mexico,
      connected in Cuba, across which they could effectively exchange alleles. However,
      introgression appears highly localized, suggesting that oak species boundaries
      and their geographic ranges have remained relatively stable over evolutionary
      time. 

PMID- 26299375
TI  - Atypical bullous pemphigoid with extensive cutaneous and mucosal erosions
      associated with chronic lymphocytic leukemia.

PMID- 26299376
TI  - Receptor-Guided De Novo Design of Dengue Envelope Protein Inhibitors.
AB  - Inhibitor design associated with the dynamics of dengue envelope protein at pre
      fusion stage is a prominent strategy to interfere fusion transition of dengue
      virus with the host cell membrane. Receptor-guided de novo inhibitors were
      designed based on the knowledge of co-crystallized detergent, beta-octyl
      glucoside. Pharmacophore features distribution showed the preference of aromatic
      groups with H bonding features connected to aliphatic bulky group as the skeleton
      for inhibitor design. Molecular dynamic simulations revealed (2R)-2-[(6-amino-1
      oxohexan-2-yl)amino]-4-[6-(4-phenylpiperidine-1-yl)-1,2-benzoxazol-3-yl]butanoate
      as the probable binder which developed extensive conservative interactions
      despite the local pocket residues movements especially from kl beta-hairpin, the
      key structural unit for initiating conformational changes required for fusion
      transition. The electronic and hydrophobic potentials also indicated that
      butanoate molecule as the initial lead for envelope protein inhibitors. 

PMID- 26299377
TI  - Molecular Cloning and Expression Analysis of a Catalase Gene (NnCAT) from Nelumbo
      nucifera.
AB  - Rapid amplification cDNA end (RACE) assay was established to achieve the complete
      cDNA sequence of a catalase gene (NnCAT) from Nelumbo nucifera. The obtained full
      length cDNA was 1666 bp in size and contained a 1476-bp open reading frame. The
      3D structural model of NnCAT was constructed by homology modeling. The putative
      NnCAT possessed all the main characteristic amino acid residues and motifs of
      catalase (CAT) protein family, and the phylogenetic analysis revealed that NnCAT
      grouped together with high plants. Moreover, recombinant NnCAT showed the CAT
      activity (758 U/mg) at room temperature, holding high activity during temperature
      range of 20-50  degrees C, then the optimal pH of recombinant protein was
      assessed from pH 4 to pH 11. Additionally, real-time PCR assay demonstrated that
      NnCAT mRNA was expressed in various tissues of N. nucifera, with the highest
      expression in young leaf and lowest level in the root, and mRNA level of NnCAT
      was significantly augmented in response to short-time mechanical wounding.
      Different expression pattern of NnCAT gene suggested that NnCAT probably played a
      defensive role in the initial stages of oxidative stress, regulating the level of
      reactive oxygen species (ROS) by extracellular stimuli such as short-time
      mechanical wounding. 

PMID- 26299378
TI  - Utilization of High-Fructose Corn Syrup for Biomass Production Containing High
      Levels of Docosahexaenoic Acid by a Newly Isolated Aurantiochytrium sp. YLH70.
AB  - High-fructose corn syrup (HFCS) is an agro-source product and has been the most
      commonly used substitute for sugar as sweetener in food industry due to its low
      price and high solution property. In this study, the F55 HFCS, rich in fructose
      and glucose, was first tested for biomass and docosahexaenoic acid productions as
      a mixed carbon source by a newly isolated Aurantiochytrium sp.YLH70. After the
      compositions of the HFCS media were optimized, the results showed that the HFCS
      with additions of metal ion and vitamin at low concentrations was suitable for
      biomass and docosahexaenoic acid productions and the metal ion and sea salt had
      the most significant effects on biomass production. During the 5-l fed-batch
      fermentation, total HFCS containing 180 g l(-1) reducing sugar was consumed and
      yields of biomass, lipid, and DHA could reach 78.5, 51, and 20.1 g l(-1),
      respectively, at 114 h. Meanwhile, the daily productivity and the reducing sugar
      conversion yield for docosahexaenoic acid were up to 4.23 g l(-1)day(-1) and 0.11
      g g(-1). The fatty acid profile of Aurantiochytrium sp.YLH70 showed that 46.4% of
      total fatty acid was docosahexaenoic acid, suggesting that Aurantiochytrium
      sp.YLH70 was a promising DHA producer.

PMID- 26299379
TI  - Accommodating lithium into 3D current collectors with a submicron skeleton
      towards long-life lithium metal anodes.
AB  - Lithium metal is one of the most attractive anode materials for electrochemical
      energy storage. However, the growth of Li dendrites during electrochemical
      deposition, which leads to a low Coulombic efficiency and safety concerns, has
      long hindered the application of rechargeable Li-metal batteries. Here we show
      that a 3D current collector with a submicron skeleton and high electroactive
      surface area can significantly improve the electrochemical deposition behaviour
      of Li. Li anode is accommodated in the 3D structure without uncontrollable Li
      dendrites. With the growth of Li dendrites being effectively suppressed, the Li
      anode in the 3D current collector can run for 600 h without short circuit and
      exhibits low voltage hysteresis. The exceptional electrochemical performance of
      the Li-metal anode in the 3D current collector highlights the importance of
      rational design of current collectors and reveals a new avenue for developing Li
      anodes with a long lifespan. 

PMID- 26299380
TI  - Goal setting and lifestyle changes in a nurse-led counselling programme for leg
      ulcer patients: an explorative analysis of nursing records.
AB  - AIMS AND OBJECTIVES: To describe goals set in individual nurse-led lifestyle
      counselling sessions in leg ulcer patients, and to explore patient and goal
      characteristics in relation to health behaviour change. BACKGROUND: Goal setting
      is increasingly used in nurse-led counselling programmes, but the delivery is
      often unknown, especially in patient groups for which only recently programmes
      have been developed, such as patients with venous leg ulcers. DESIGN: A secondary
      analysis of data collected in the intervention arm of a randomised clinical trial
      of counselling sessions in venous leg ulcer patients. METHODS: Nursing records (n
      = 71) were explored for the number of goals set, topic, quality and course of
      goals during the trajectory. Furthermore, goals and patient characteristics were
      compared in relation to health behaviour change. RESULTS: Forty-one patients
      (58%) succeeded in changing their behaviour after setting a goal. Setting goals
      for conducting leg exercises was chosen by most patients in this study, goals for
      adherence with compression therapy were chosen the least. Sixty-eight per cent of
      the goals met criteria for being Specific, Measurable and Time-bound. Patients
      who achieved behaviour change were significantly younger compared to the patients
      who did not. Except for age, there were no differences in characteristics between
      the group that did and did not achieve behaviour change. CONCLUSIONS: Goal
      setting could be improved by setting goals more Specific, Measurable and Time
      bound, and by setting goals on an essential topic for behaviour change. This
      explorative study did not show that goal characteristics, including the quality
      of goals, were related to patients' behaviour change. RELEVANCE TO CLINICAL
      PRACTICE: The delivery of goal setting in this programme, and most likely in
      similar programmes, could be improved. Regular quality checks in daily goal
      setting practice should be considered. More research is needed into how to best
      provide health promotion to frail and elderly people.

PMID- 26299382
TI  - A case of human to human transmission of orf between mother and child.
AB  - Orf is caused by a parapoxvirus. In adults, it is commonly associated with
      specific occupations, whereas cases in children tend to be associated with
      household or recreational exposure. Spontaneous recovery usually occurs within 6
      weeks. Infection in humans is believed to be through exposure to an infected
      animal or fomite. We present a case of a 13-month-old boy who was exposed to orf
      through his mother, a farmer, who had contracted the disease through
      administering medication to an infected animal. We believe that this may
      represent only the fifth case of human to human transmission of orf reported in
      the literature. 

PMID- 26299383
TI  - Progestogens and risk of breast cancer: a link between bone and breast?
AB  - This article reviews the data supporting the role of receptor activator of the
      nuclear factor kappa (RANK) and its ligand, RANKL, in progestogen-induced breast
      cancer. Both experimental and clinical studies have been included. The expression
      of both RANK and RANKL has been described in epithelial cells of both mice and
      humans. Experiments of gain and loss of function in mice have shown that
      RANK/RANKL mediate alveologenesis during pregnancy or the estrous cycle.
      Moreover, the participation of the RANK/RANKL has been detected in models of
      breast carcinogenesis associated with progestogens-like medroxyprogesterone
      acetate. Recent clinical studies have found that the expression of RANK is
      associated with parameters of aggressiveness of the tumor. 

PMID- 26299384
TI  - Capillary isoelectric focusing-mass spectrometry: Coupling strategies and
      applications.
AB  - IEF on immobilized pH gradient strips is a widespread tool for protein
      separation, especially as first dimension in commonly utilized 2DE. In the latter
      arrangement, separations are based on two orthogonal molecular characteristics
      according to pI in the first and molecular weight in the second dimension.
      However, the approach is time consuming, quantification is difficult and MS can
      be applied only offline. Capillary IEF and related IEF techniques in combination
      with MS provide similar information. The major benefits are high mass resolution
      and mass accuracy, reproducibility, speed, automation, and quantification by
      using a high-resolution mass spectrometer. However, online hyphenation of CIEF
      with MS is interfered by the ampholytes, acids, and bases needed for high
      resolution IEF. This review will give an overview about important coupling
      techniques, like low ampholyte concentration, interim separation by
      chromatography, or the use of a dialysis interface to separate the analytes from
      interfering substances. It is focused on strategies which allow sensitive MS
      detection of CIEF-separated analytes. In addition, proteomic and
      biopharmaceutical applications of capillary IEF techniques combined with MS are
      briefly summarized.

PMID- 26299381
TI  - Safety of Retinopathy of Prematurity Examination and Imaging in Premature
      Infants.
AB  - OBJECTIVES: To describe adverse events (AEs) and noteworthy clinical or ocular
      findings associated with retinopathy of prematurity (ROP) evaluation procedures.
      STUDY DESIGN: Descriptive analysis of predefined AEs and noteworthy findings
      reported in a prospective observational cohort study of infants <1251 g birth
      weight who had ROP study visits consisting of both binocular indirect
      ophthalmoscopy (BIO) and digital retinal imaging. We compared infant
      characteristics during ROP visits with and without AEs. We compared respiratory
      support, nutrition, and number of apnea, bradycardia, or hypoxia events 12 hours
      before and after ROP visits. RESULTS: A total of 1257 infants, mean birth weight
      802 g, had 4263 BIO and 4048 imaging sessions (total 8311 procedures). No serious
      AEs were related to ROP visits. Sixty-five AEs were reported among 61 infants for
      an AE rate of 4.9% infants (61/1257) or 0.8% total procedures (65/8311 BIO +
      imaging). Most AEs were due to apnea, bradycardia, and/or hypoxia (68%),
      tachycardia (16%), or emesis (8%). At ROP visit, infants with AEs, compared with
      those without, were more likely to be on mechanical ventilation (26% vs 12%, P =
      .04) even after adjustment for weight and postmenstrual age. Noteworthy clinical
      findings were reported during 8% BIO and 15% imaging examinations. Respiratory
      and nutrition support were not significantly different before and after ROP
      evaluations. CONCLUSIONS: Retinal imaging by nonphysicians combined with BIO was
      safe. Noteworthy clinical findings occurred during both procedures. Ventilator
      support was a risk factor for AEs. Monitoring rates of AEs and noteworthy
      findings are important to the safe implementation of ROP imaging protocols. TRIAL
      REGISTRATION: Clinicaltrials.gov: NCT01264276.

PMID- 26299385
TI  - [Elective extubation during skin-to-skin contact in the extremely premature
      newborn].

PMID- 26299387
TI  - Clinicopathological analysis of mechanic's hand associated with dermatomyositis.
AB  - Mechanic's hand is often seen in the fingers of patients with dermatomyositis and
      is frequently associated with anti-aminoacyl-transfer RNA synthetase
      autoantibodies and interstitial lung disease. We analysed the clinical symptoms
      of 50 patients with dermatomyositis who had visited our department, 26 of whom
      also had mechanic's hand. A histological examination was carried out in 16 of the
      26 cases, which revealed hyperkeratosis in all cases and colloid bodies in the
      epidermis in 15 cases. The number of cases of interstitial lung disease in
      patients with mechanic's hand (22/26, 85%) was significantly higher than that in
      those without mechanic's hand (12/24, 50%) (P < 0.05). Mechanic's hand is an
      important skin lesion of dermatomyositis, and increases the likelihood of
      interstitial lung disease.

PMID- 26299388
TI  - Report of a delayed seizure after low frequency repetitive Transcranial Magnetic
      Stimulation in a chronic stroke patient.

PMID- 26299386
TI  - Suppressive mechanisms in visual motion processing: From perception to
      intelligence.
AB  - Perception operates on an immense amount of incoming information that greatly
      exceeds the brain's processing capacity. Because of this fundamental limitation,
      the ability to suppress irrelevant information is a key determinant of perceptual
      efficiency. Here, I will review a series of studies investigating suppressive
      mechanisms in visual motion processing, namely perceptual suppression of large,
      background-like motions. These spatial suppression mechanisms are adaptive,
      operating only when sensory inputs are sufficiently robust to guarantee
      visibility. Converging correlational and causal evidence links these behavioral
      results with inhibitory center-surround mechanisms, namely those in cortical area
      MT. Spatial suppression is abnormally weak in several special populations,
      including the elderly and individuals with schizophrenia-a deficit that is
      evidenced by better-than-normal direction discriminations of large moving
      stimuli. Theoretical work shows that this abnormal weakening of spatial
      suppression should result in motion segregation deficits, but direct behavioral
      support of this hypothesis is lacking. Finally, I will argue that the ability to
      suppress information is a fundamental neural process that applies not only to
      perception but also to cognition in general. Supporting this argument, I will
      discuss recent research that shows individual differences in spatial suppression
      of motion signals strongly predict individual variations in IQ scores. 

PMID- 26299389
TI  - Hypoglycemia and risk of vascular events and mortality: a systematic review and
      meta-analysis.
AB  - AIMS: Hypoglycemia has been associated with adverse outcomes in patients with
      diabetes and critical illness. However, such associations in these populations
      have not been systematically examined. METHODS: We conducted a systematic review
      and meta-analysis of longitudinal follow-up cohort studies to investigate the
      associations between hypoglycemia and various adverse outcomes. RESULTS: After
      removing duplicates and critically appraising all screened citations, a total of
      19 eligible studies were included. As demonstrated by random-effects meta
      analysis, hypoglycemia was strongly associated with a higher risk of adverse
      events (HR 1.90, 95 % CI 1.63-2.20; P < 0.001). Comparable risk ratios were shown
      in prespecified stratified analyses investigating above association for different
      study endpoints, in patients with or without critical illness, in patients with
      and without diabetes (from 1.47 to 3.31; p for interaction or heterogeneity
      >0.1). Additionally, a dose-dependent relationship between the severity of
      hypoglycemia and adverse vascular events and mortality (HR for mild hypoglycemia:
      1.68, 95 % CI 1.25-2.26; P < 0.001 and HR for severe hypoglycemia: 2.33, 95 % CI
      2.07-2.61; P < 0.001; p for trend 0.02) was observed. Suggested by a bias
      analysis, the above observations were unlikely to have resulted from unmeasured
      confounding parameters. CONCLUSIONS: This is the first study demonstrating that
      hypoglycemia was associated with comparable risk ratios in different study
      populations and various study endpoints, and a trend of a dose-dependent
      relationship between hypoglycemia severity and adverse events. The findings of
      this systematic review support the speculation that hypoglycemia is a risk factor
      for adverse vascular events and mortality.

PMID- 26299390
TI  - Neuronal migration disorders: Focus on the cytoskeleton and epilepsy.
AB  - A wide spectrum of focal, regional, or diffuse structural brain abnormalities,
      collectively known as malformations of cortical development (MCDs), frequently
      manifest with intellectual disability (ID), epilepsy, and/or autistic spectrum
      disorder (ASD). As the acronym suggests, MCDs are perturbations of the normal
      architecture of the cerebral cortex and hippocampus. The pathogenesis of these
      disorders remains incompletely understood; however, one area that has provided
      important insights has been the study of neuronal migration. The amalgamation of
      human genetics and experimental studies in animal models has led to the
      recognition that common genetic causes of neurodevelopmental disorders, including
      many severe epilepsy syndromes, are due to mutations in genes regulating the
      migration of newly born post-mitotic neurons. Neuronal migration genes often,
      though not exclusively, code for proteins involved in the function of the
      cytoskeleton. Other cellular processes, such as cell division and axon/dendrite
      formation, which similarly depend on cytoskeletal functions, may also be
      affected. We focus here on how the susceptibility of the highly organized
      neocortex and hippocampus may be due to their laminar organization, which
      involves the tight regulation, both temporally and spatially, of gene expression,
      specialized progenitor cells, the migration of neurons over large distances and a
      birthdate-specific layering of neurons. Perturbations in neuronal migration
      result in abnormal lamination, neuronal differentiation defects, abnormal
      cellular morphology and circuit formation. Ultimately this results in
      disorganized excitatory and inhibitory activity leading to the symptoms observed
      in individuals with these disorders.

PMID- 26299391
TI  - Inflammation without neuronal death triggers striatal neurogenesis comparable to
      stroke.
AB  - Ischemic stroke triggers neurogenesis from neural stem/progenitor cells (NSPCs)
      in the subventricular zone (SVZ) and migration of newly formed neuroblasts toward
      the damaged striatum where they differentiate to mature neurons. Whether it is
      the injury per se or the associated inflammation that gives rise to this
      endogenous neurogenic response is unknown. Here we showed that inflammation
      without corresponding neuronal loss caused by intrastriatal lipopolysaccharide
      (LPS) injection leads to striatal neurogenesis in rats comparable to that after a
      30 min middle cerebral artery occlusion, as characterized by striatal DCX+
      neuroblast recruitment and mature NeuN+/BrdU+ neuron formation. Using global gene
      expression analysis, changes in several factors that could potentially regulate
      striatal neurogenesis were identified in microglia sorted from SVZ and striatum
      of LPS-injected and stroke-subjected rats. Among the upregulated factors, one
      chemokine, CXCL13, was found to promote neuroblast migration from neonatal mouse
      SVZ explants in vitro. However, neuroblast migration to the striatum was not
      affected in constitutive CXCL13 receptor CXCR5(-/-) mice subjected to stroke.
      Infarct volume and pro-inflammatory M1 microglia/macrophage density were
      increased in CXCR5(-/-) mice, suggesting that microglia-derived CXCL13, acting
      through CXCR5, might be involved in neuroprotection following stroke. Our
      findings raise the possibility that the inflammation accompanying an ischemic
      insult is the major inducer of striatal neurogenesis after stroke.

PMID- 26299392
TI  - The non-take up of long-term care benefit in France: A pecuniary motive?
AB  - With aging populations, European countries face difficult challenges. In 2002,
      France implemented a public allowance program (APA) offering financial support to
      the disabled elderly for their long-term care (LTC) needs. Although currently
      granted to 1.2 million people, it is suspected that some of those eligible do not
      claim it--presenting a non-take-up behavior. The granting of APA is a
      decentralized process, with 94 County Councils (CC) managing it, with wide room
      for local interpretation. This spatial heterogeneity in the implementation of the
      program creates the conditions for a "quasi-natural experiment", and provides the
      opportunity to study the demand for APA in relation to variations in CCs'
      "generosity" in terms of both eligibility and subsidy rate for LTC. We use a
      national health survey and administrative data in a multilevel model controlling
      for geographical, cultural and political differences between counties. The
      results show that claiming for APA is associated with the "generosity" of CCs:
      the population tends to apply less for the allowance if the subsidy rate is in
      average lower. This pecuniary trade-off, revealed by our study, can have strong
      implications for the well-being of the elderly and their relatives.

PMID- 26299393
TI  - Violent video game players and non-players differ on facial emotion recognition.
AB  - Violent video game playing has been associated with both positive and negative
      effects on cognition. We examined whether playing two or more hours of violent
      video games a day, compared to not playing video games, was associated with a
      different pattern of recognition of five facial emotions, while controlling for
      general perceptual and cognitive differences that might also occur. Undergraduate
      students were categorized as violent video game players (n = 83) or non-gamers (n
      = 69) and completed a facial recognition task, consisting of an emotion
      recognition condition and a control condition of gender recognition.
      Additionally, participants completed questionnaires assessing their video game
      and media consumption, aggression, and mood. Violent video game players
      recognized fearful faces both more accurately and quickly and disgusted faces
      less accurately than non-gamers. Desensitization to violence, constant exposure
      to fear and anxiety during game playing, and the habituation to unpleasant
      stimuli, are possible mechanisms that could explain these results. Future
      research should evaluate the effects of violent video game playing on emotion
      processing and social cognition more broadly.

PMID- 26299394
TI  - Residual Elimination Algorithm Enhancements to Improve Foot Motion Tracking
      During Forward Dynamic Simulations of Gait.
AB  - Patient-specific gait optimizations capable of predicting post-treatment changes
      in joint motions and loads could improve treatment design for gait-related
      disorders. To maximize potential clinical utility, such optimizations should
      utilize full-body three-dimensional patient-specific musculoskeletal models,
      generate dynamically consistent gait motions that reproduce pretreatment marker
      measurements closely, and achieve accurate foot motion tracking to permit
      deformable foot-ground contact modeling. This study enhances an existing residual
      elimination algorithm (REA) Remy, C. D., and Thelen, D. G., 2009, "Optimal
      Estimation of Dynamically Consistent Kinematics and Kinetics for Forward Dynamic
      Simulation of Gait," ASME J. Biomech. Eng., 131(3), p. 031005) to achieve all
      three requirements within a single gait optimization framework. We investigated
      four primary enhancements to the original REA: (1) manual modification of tracked
      marker weights, (2) automatic modification of tracked joint acceleration curves,
      (3) automatic modification of algorithm feedback gains, and (4) automatic
      calibration of model joint and inertial parameter values. We evaluated the
      enhanced REA using a full-body three-dimensional dynamic skeletal model and
      movement data collected from a subject who performed four distinct gait patterns:
      walking, marching, running, and bounding. When all four enhancements were
      implemented together, the enhanced REA achieved dynamic consistency with lower
      marker tracking errors for all segments, especially the feet (mean root-mean
      square (RMS) errors of 3.1 versus 18.4 mm), compared to the original REA. When
      the enhancements were implemented separately and in combinations, the most
      important one was automatic modification of tracked joint acceleration curves,
      while the least important enhancement was automatic modification of algorithm
      feedback gains. The enhanced REA provides a framework for future gait
      optimization studies that seek to predict subject-specific post-treatment gait
      patterns involving large changes in foot-ground contact patterns made possible
      through deformable foot-ground contact models.

PMID- 26299395
TI  - Copper catalyzed sequential arylation-oxidative dimerization of o-haloanilides:
      synthesis of dimeric HPI alkaloids.
AB  - In this communication, we report a copper catalyzed sequential arylation
      oxidative dimerization reaction as the key step for the synthesis of
      hexahydropyrroloindole alkaloids (+)-chimonanthine, (+)-folicanthine and (-)
      calycanthine. 

PMID- 26299396
TI  - Extended follow-up of neurological, cognitive, behavioral and academic outcomes
      after severe abusive head trauma.
AB  - Studies about long-term outcome following abusive head trauma (AHT) are scarce.
      The aims of this study were to report long-term neurological, cognitive,
      behavioral and academic outcomes, ongoing treatments and/or rehabilitation,
      several years after AHT diagnosis, and factors associated with outcome. In this
      retrospective study, all patients admitted to a single rehabilitation unit
      following AHT between 1996 and 2005, with subsequent follow-up exceeding 3 years,
      were included. Medical files were reviewed and a medical interview was performed
      with parents on the phone when possible. The primary outcome measure was the
      Glasgow Outcome Scale (GOS). Forty-seven children (out of 66) met the inclusion
      criteria (mean age at injury 5.7 months; SD=3.2). After a median length of follow
      up of 8 years (range 3.7-12), only seven children (15%) had "good outcome"
      (normal life - GOS I) and 19 children (40%) presented with severe neurological
      impairment (GOS III and IV). Children sustained epilepsy (38%), motor deficits
      (45%), visual deficit (45%), sleep disorders (17%), language abnormalities (49%),
      attention deficits (79%) and behavioral disorders (53%). Most children (83%) had
      ongoing rehabilitation. Only 30% followed a normal curriculum, whereas 30%
      required special education services. Children with better overall outcome (GOS I
      and II) had significantly higher educated mothers than those with worse outcomes
      (GOS III and IV): graduation from high school 59% and 21% respectively (p=0.006).
      This study highlights the high rate of severe sequelae and health care needs
      several years post-AHT, and emphasizes the need for extended follow-up of
      medical, cognitive and academic outcomes. 

PMID- 26299397
TI  - Bloodletting for non-medical reasons: what about safety and quality?

PMID- 26299398
TI  - Invasive Thymoma Protruding into the Superior Vena Cava through the Thymic Vein.
AB  - We report a rare case of protrusion of an invasive thymoma with intraluminal
      growth through the thymic vein into the superior vena cava (SVC) without direct
      invasion of the vessel walls. The tumor and left brachiocephalic vein were
      resected, and the tumor in the SVC was removed with temporal bypass of the right
      brachiocephalic vein and right auricle. Histopathological finding showed that the
      thymoma had protruded via a thymic vein. During resection of a thymoma, a
      detailed examination of thymic vein is necessary to ensure that no tumor tissue
      remains in the vessels. 

PMID- 26299399
TI  - A nuclear fraction of turnip crinkle virus capsid protein is important for
      elicitation of the host resistance response.
AB  - The N-terminal 25 amino acids (AAs) of turnip crinkle virus (TCV) capsid protein
      (CP) are recognized by the resistance protein HRT to trigger a hypersensitive
      response (HR) and systemic resistance to TCV infection. This same region of TCV
      CP also contains a motif that interacts with the transcription factor TIP, as
      well as a nuclear localization signal (NLS). However, it is not yet known whether
      nuclear localization of TCV CP is needed for the induction of HRT-mediated HR and
      resistance. Here we present new evidence suggesting a tight correlation between
      nuclear inclusions formed by CP and the manifestation of HR. We show that a
      fraction of TCV CP localized to cell nuclei to form discrete inclusion-like
      structures, and a mutated CP (R6A) known to abolish HR failed to form nuclear
      inclusions. Notably, TIP-CP interaction augments the inclusion-forming activity
      of CP by tethering inclusions to the nuclear membrane. This TIP-mediated
      augmentation is also critical for HR resistance, as another CP mutant (R8A) known
      to elicit a less restrictive HR, though still self-associated into nuclear
      inclusions, failed to direct inclusions to the nuclear membrane due to its
      inability to interact with TIP. Finally, exclusion of CP from cell nuclei
      abolished induction of HR. Together, these results uncovered a strong correlation
      between nuclear localization and nuclear inclusion formation by TCV CP and
      induction of HR, and suggest that CP nuclear inclusions could be the key trigger
      of the HRT-dependent, yet TIP-reinforced, resistance to TCV. 

PMID- 26299401
TI  - Experimental and Modeling Study of Solvent Diffusion in PDMS for Nanoparticle
      Polymer Cosuspension Imprint Lithography.
AB  - This study is the first that focuses on solvent migration in a
      polydimethylsiloxane (PDMS) stamp during the imprint lithography of ZnO
      poly(methyl methacrylate) (PMMA) hybrid suspensions. Using suspensions with
      varying solids loading levels and ZnO/PMMA ratios, the uptake of the anisole
      solvent in the stamp is evaluated as a function of time. Laser confocal
      microscopy is employed as a unique technique to measure the penetration depth of
      the solvent into the stamp. The suspension solids loading affects the anisole
      saturation depth in the PDMS stamp. For the suspensions with low solids loading,
      the experimental data agree with the model for non-Fickian diffusion through a
      rubbery-elastic polymer. For the suspensions with high solids loading, the data
      agree more with a sigmoidal diffusion curve, reflecting the rubbery-viscous
      behavior of a swelling polymer. This difference is due to the degree of swelling
      in the PDMS. Higher solids loadings induce more swelling because the rate of
      anisole diffusing into the stamp is increased, likely due to the less dense
      buildup of the solids as the suspension dries. 

PMID- 26299400
TI  - Effect of over-the-counter fluoridated products regimens on root caries
      inhibition.
AB  - OBJECTIVE: This study aimed to evaluate the effect of fluoridated dentifrice (FD)
      and mouthwash (FM) under different treatment regimens on root caries (RC)
      inhibition. METHODS: Dual-species biofilms formed by Streptococcus mutans and
      Lactobacillus casei were grown on the surface of bovine root dentine slabs which
      were exposed during 3 consecutive days to one of the following treatments: T1
      distilled and deionized water 3*/day; T2-FD (1450ppmF) 2*/day; T3-FD 2*/day+FM
      (226ppmF) 1*/day; T4-FD 3*/day. Viable microorganisms counts were performed after
      4 days of biofilm formation. Percentage of surface microhardness change (%SMC),
      lesion depth (LD; MUm), integrated mineral loss (IML; vol%*MUm) and the
      percentages of change (Delta%) in the ratio of fluorapatite (FAp/amide) and
      hydroxiapatite (HAp/amide) were calculated. RESULTS: Minor changes were found on
      microbial counts in response to different treatments (p<0.05). %SMC in T4 was
      statistically lower compared with T2, but with no significant difference compared
      with T3. LD of slabs treated with T4 was statistically lower compared with T2 and
      T3, which were not significantly different between them. No significant
      differences were found for IML, FAp and HAp among the fluoridated treatments
      (p>0.05). CONCLUSION: The use of FD 3*/day may be more effective than the use of
      FD 2*/day or the tested association between FD and FM on RC inhibition.

PMID- 26299402
TI  - Droplets merging through wireless ultrasonic actuation.
AB  - A new technique of droplets merging through wireless ultrasonic actuation has
      been proposed and experimentally investigated in this work. The proposed method
      is based on the principle of resonant inductive coupling and piezoelectric
      resonance. When a mechanical vibration is excited in a piezoelectric plate, the
      ultrasonic vibration transmitted to the droplets placed on its surface and
      induces merging. It has been observed that the merging rate of water droplets
      depends on the operating frequency, mechanical vibration of piezoelectric plate,
      separation distance between the droplets, and volume of droplets. The
      investigated technique of droplets merging through piezoelectric actuation is
      quite useful for microfluidics, chemical and biomedical engineering applications.

PMID- 26299405
TI  - How pervasive is biotic homogenization in human-modified tropical forest
      landscapes?
AB  - Land-cover change and ecosystem degradation may lead to biotic homogenization,
      yet our understanding of this phenomenon over large spatial scales and different
      biotic groups remains weak. We used a multi-taxa dataset from 335 sites and 36
      heterogeneous landscapes in the Brazilian Amazon to examine the potential for
      landscape-scale processes to modulate the cumulative effects of local
      disturbances. Biotic homogenization was high in production areas but much less in
      disturbed and regenerating forests, where high levels of among-site and among
      landscape beta-diversity appeared to attenuate species loss at larger scales. We
      found consistently high levels of beta-diversity among landscapes for all land
      cover classes, providing support for landscape-scale divergence in species
      composition. Our findings support concerns that beta-diversity has been
      underestimated as a driver of biodiversity change and underscore the importance
      of maintaining a distributed network of reserves, including remaining areas of
      undisturbed primary forest, but also disturbed and regenerating forests, to
      conserve regional biota. 

PMID- 26299406
TI  - Long term side effects of adjuvant chemotherapy in patients with early breast
      cancer.
AB  - Adjuvant systemic therapy along with screening has been key to the observed
      improvements in disease-free and overall survival (DFS/OS) in breast cancer.
      Improvements in overall survival already take into account therapy related
      toxicities that can result in death. However, this measure alone does not
      adequately capture the impact on health-related quality of life. Therefore, it is
      important to examine the prevalence, frequency and short/long-term impact of
      therapy-related toxicities, identify patients who might be at greatest risk.
      Ultimately decisions regarding expected therapy benefits (relative and absolute
      percentage improvements in DFS/OS) must be made against a background of known
      potential harms. For many patients with early breast cancer (EBC), their risk of
      recurrence is not zero but is small. At the same time, for many therapies for
      early stage breast cancer, the risk of serious side effects is small but is not
      zero. As we better understand the long-term side effects of adjuvant chemotherapy
      and targeted therapy, it becomes critical to integrate our growing understanding
      of breast cancer biology with standard high-quality histopathologic measures to
      better identify the patients most likely to benefit from the various options for
      combined multimodality therapy. Hence, we must strive against the notion of
      recommending adjuvant systemic chemotherapy "just in case." This article focuses
      on the long-term side effects of adjuvant chemotherapy in patients with EBC.

PMID- 26299407
TI  - Characterization of two cation diffusion facilitators NpunF0707 and NpunF1794 in
      Nostoc punctiforme.
AB  - AIMS: To characterize genes involved in maintaining homeostatic levels of zinc in
      the cyanobacterium Nostoc punctiforme. METHODS AND RESULTS: Metal efflux
      transporters play a central role in maintaining homeostatic levels of trace
      elements such as zinc. Sequence analyses of the N. punctiforme genome identified
      two potential cation diffusion facilitator (CDF) metal efflux transporters,
      Npun_F0707 (Cdf31) and Npun_F1794 (Cdf33). Deletion of either Cdf31or Cdf33
      resulted in increased zinc retention over 3 h. Interestingly, Cdf31(-) and Cdf33(
      ) mutants showed no change in sensitivity to zinc exposure in comparison with the
      wild type, suggesting some compensatory capacity for the loss of each other.
      Using qRT-PCR, a possible interaction was observed between the two cdf's, where
      the Cdf31(-) mutant had a more profound effect on cdf33 expression than Cdf33(-)
      did on cdf31. Over-expression of Cdf31 and Cdf33 in ZntA(-) - and ZitB(-) 
      deficient Escherichia coli revealed function similarities between the ZntA and
      ZitB of E. coli and the cyanobacterial transporters. CONCLUSIONS: The data
      presented shed light on the function of two important transporters that regulate
      zinc homeostasis in N. punctiforme. SIGNIFICANCE AND IMPACT OF THE STUDY: This
      study shows for the first time the functional characterization of two
      cyanobacterial zinc efflux proteins belonging to the CDF family.

PMID- 26299409
TI  - RP-HPLC analysis of seco-iridoid glycoside swertiamarin from different Swertia
      species.
AB  - Genus Swertia is valued for its great medicinal potential; mainly Swertia
      chirayita (Roxb. ex Fleming) H. Karst. is used in traditional medicine for a wide
      range of diseases. Seco-iridoid glycosides like swertiamarin is referred with
      enormous pharmacological potentials. The aim of the study was to identify a
      suitable substitute to S. chirayita by quantifying seco-iridoid swertiamarin from
      five different Swertia species endemic to the Western Ghats. The reverse-phase
      high-performance liquid chromatography diode array detector analyses were
      performed and chromatographic separation was achieved on a Lichrospher 100, C18e
      (5 um) column (250-4.6 mm). A mobile phase consisting of acetonitrile and water
      (25:75) was used for separation. Results indicated that the concentration of the
      marker compound has been found to vary largely between and within the species
      from different localities. The content of swertiamarin was the highest in S.
      chirayita compared to the other species studied herein, advocating the use of
      Swertia minor as an alternate source to S. chirayita.

PMID- 26299408
TI  - Midgut bacterial communities in the giant Asian honeybee (Apis dorsata) across 4
      developmental stages: A comparative study.
AB  - Bacterial communities are known to play important roles during the developmental
      stages of insects, but current knowledge of bacteria associated with the midgut
      of Apis dorsata, the giant Asian honeybee, is limited. Using polymerase chain
      reaction-denaturing gradient gel electrophoresis analysis (PCR-DGGE) and 16S rRNA
      sequencing, the aim of this study was to determine the dynamics of bacterial
      community structure across four A. dorsata life stages in different geographical
      locations. The results reveal that bacterial diversity increased as the bee
      progressed through larval stage to newly emerged worker and old worker. However,
      in the pupal stage, no bands identified as bacteria could be observed. Overall, 2
      bacterial phyla (Proteobacteria and Firmicutes) and 4 classes
      (Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, and Bacilli) were
      identified, but the frequency varied among the different stages and locations.
      The classes of Gammaproteobacteria and Bacilli dominated among larval, newly
      emerged worker and old worker developmental stages.

PMID- 26299410
TI  - Thermal evolution of cobalt deposits on Co3O4(111): atomically dispersed cobalt,
      two-dimensional CoO islands, and metallic Co nanoparticles.
AB  - Cobalt oxide nanomaterials show high activity in several catalytic reactions
      thereby offering the potential to replace noble metals in some applications. We
      have developed a well-defined model system for partially reduced cobalt oxide
      materials aiming at a molecular level understanding of cobalt-oxide-based
      catalysis. Starting from a well-ordered Co3O4(111) film on Ir(100), we modified
      the surface by deposition of metallic cobalt. Growth, structure, and adsorption
      properties of the cobalt-modified surface were investigated by scanning tunneling
      microscopy (STM), low-energy electron diffraction (LEED), and infrared reflection
      absorption spectroscopy (IRAS) using CO as a probe molecule. The deposition of a
      submonolayer of cobalt at 300 K leads to the formation of atomically dispersed
      cobalt ions distorting the surface layer of the Co3O4 film. Upon annealing to 500
      K the Co ions are incorporated into the surface layer forming ordered two
      dimensional CoO islands on the Co3O4 grains. At 700 K, Co ions diffuse from the
      CoO islands into the bulk and the ordered Co3O4(111) surface is restored.
      Deposition of larger amounts of Co at 300 K leads to formation of metallic Co
      aggregates on the dispersed cobalt phase. The metallic particles sinter at 500 K
      and diffuse into the bulk at 700 K. Depending on the degree of bulk reduction,
      extended Co3O4 grains switch to the CoO(111) structure. All above structures show
      characteristic CO adsorption behavior and can therefore be identified by IR
      spectroscopy of adsorbed CO. 

PMID- 26299411
TI  - Frequency of progression from acute to chronic pancreatitis and risk factors: a
      meta-analysis.
AB  - BACKGROUND & AIM: Acute pancreatitis (AP) and chronic pancreatitis (CP)
      traditionally have been thought to be distinct diseases, but there is evidence
      that AP can progress to CP. Little is known about the mechanisms of pancreatitis
      progression. We performed a meta-analysis to quantify the frequency of transition
      of AP to CP and identify risk factors for progression. METHODS: We searched
      PubMed, Scopus, and Embase for studies of patients with AP who developed CP,
      published from 1966 through November 2014. Pooled prevalence and 95% confidence
      intervals (CIs) were calculated for these outcomes, and sensitivity, subgroup,
      and meta-regression analyses were conducted. RESULTS: We analyzed 14 studies,
      which included a total of 8492 patients. The pooled prevalence of recurrent AP
      was 22% (95% CI, 18%-26%), and the pooled prevalence of CP was 10% (95% CI, 6%
      15%). Sensitivity analyses yielded a pooled prevalence of CP of 10% (95% CI, 4%
      19%) and 36% (95% CI, 20%-53%) in patients after the first occurrence and
      recurrent AP, respectively. Subgroup analyses found alcohol use and smoking to be
      the largest risk factors for the development of CP, with pooled prevalence values
      of 65% (95% CI, 48%-56%) and 61% (95% CI, 47%-73%), respectively. Meta-regression
      analysis found that men were more likely than women to transition from AP to CP.
      CONCLUSIONS: Ten percent of patients with a first episode of AP and 36% of
      patients with recurrent AP develop CP; the risk is higher among smokers,
      alcoholics, and men. Prospective clinical studies are needed to study
      pancreatitis progression.

PMID- 26299412
TI  - Heritability of Hepatic Fibrosis and Steatosis Based on a Prospective Twin Study.
AB  - BACKGROUND & AIMS: Little is known about the heritability of hepatic fibrosis,
      and the heritability of hepatic steatosis has not been assessed systematically in
      adults. We investigated the heritability of hepatic fibrosis and steatosis in a
      community-dwelling twin cohort. METHODS: We performed a cross-sectional analysis
      of a cohort of well-characterized twins residing in Southern California including
      60 pairs of twins (42 monozygotic and 18 dizygotic; average age, 45.7 +/- 22.1 y;
      average body mass index, 26.4 +/- 5.7 kg/m(2)). We collected data on medical
      history, physical examinations, fasting laboratory test results, and liver
      health; all participants underwent an advanced magnetic resonance imaging (MRI)
      examination of the liver from January 2012 through January 2015. Hepatic
      steatosis was quantified noninvasively by MRI and determined based on the proton
      density fat fraction (MRI-PDFF); liver fibrosis was measured based on stiffness
      measured by magnetic resonance elastography. RESULTS: Twenty-six of the 120
      subjects (21.7%) had nonalcoholic fatty liver disease (defined as MRI-PDFF >= 5%
      after exclusion of other causes of hepatic steatosis). The presence of hepatic
      steatosis correlated between monozygotic twins (r(2) = 0.70; P < .0001) but not
      between dizygotic twins (r(2) = 0.36; P = .2). The level of liver fibrosis also
      correlated between monozygotic twins (r(2) = 0.48; P < .002) but not between
      dizygotic twins (r(2) = 0.12; P = .7). In multivariable models adjusted for age,
      sex, and ethnicity, the heritability of hepatic steatosis (based on MRI-PDFF) was
      0.52 (95% confidence interval, 0.31-0.73; P < 1.1 * 10(-11)) and the heritability
      of hepatic fibrosis (based on liver stiffness) was 0.5 (95% confidence interval,
      0.28-0.72; P <6.1 * 10(-11)). CONCLUSIONS: A study of twins provides evidence
      that hepatic steatosis and hepatic fibrosis are heritable traits.

PMID- 26299413
TI  - Minimal hepatic encephalopathy and critical flicker frequency are associated with
      survival of patients with cirrhosis.
AB  - BACKGROUND & AIMS: Minimal hepatic encephalopathy (MHE) is associated with falls,
      traffic accidents, and overt HE. However, the association with survival is
      controversial. We assessed the effects of MHE on the long-term survival of
      patients with cirrhosis. METHODS: We performed a prospective study of 117
      consecutive patients with cirrhosis seen at a tertiary hospital in Seville, Spain
      (estimation cohort), followed by a validation study of 114 consecutive patients
      with cirrhosis seen at 4 hospitals in Spain from January 2004 through December
      2007. Patients were examined every 6 months at outpatient clinics through
      December 2013 (follow-up periods of 5 +/- 2.8 y and 4.4 +/- 3.9 y for each group,
      respectively). Cirrhosis was identified by liver biopsy, ultrasound, endoscopic
      analysis, and biochemical parameters. Liver dysfunction was determined based on
      model for end-stage liver disease (MELD) and Child-Pugh scores. All patients were
      administered the critical flicker frequency (CFF) test and psychometric hepatic
      encephalopathy scores were used to detect MHE. Survival curves were compared
      using the log-rank test and multivariable analysis was performed using Cox
      proportional hazards models. RESULTS: The distributions of Child-Pugh scores were
      as follows: 66% class A, 31% class B, and 3% class C in the estimation cohort,
      and 50% class A, 32% class B, and 18% class C in the validation cohort. In the
      estimation cohort, 24 of 35 patients (68.6%) with a CFF score less than 39 Hz
      survived for 5 years, whereas 50 of 61 patients (82%) with a CFF score of 39 Hz
      or higher survived during the follow-up period (log-rank score, 5.07; P = .024).
      Psychometric hepatic encephalopathy scores did not correlate with survival. In
      multivariable analysis, older age (hazard ratio [HR], 1.07; 95% confidence
      interval [CI], 1.02-1.12; P = .009), CFF score less than 39 Hz (HR, 4.36; 95% CI,
      1.67-11.37; P = .003), and MELD score (HR, 1.40; 95% CI, 1.21-1.63; P = .0001)
      were associated independently with survival during the follow-up period. In the
      validation cohort, CFF score less than 39 Hz and MELD score also were associated
      with patient survival during the follow-up period. MHE had no effect on the
      survival of patients with MELD scores less than 10 (among patients with CFF
      scores >=39 Hz, 94.5% survived for 5 years vs 91.9% of patients with CFF scores
      <39 Hz; log-rank score, 0.64; P = .423). Fewer patients with MELD scores of 10-15
      and MHE survived for 5 years (44.4%; 12 of 27) than those with MELD scores
      greater than 15 without MHE (61.5%; 8 of 13) (P < .05). Only 2 of 12 patients
      (16.7%) with MELD scores of 15 or higher and MHE survived for 5 years (log-rank
      score, 90.56; P = .0001). CONCLUSIONS: MHE is associated with a reduced 5-year
      survival rate of patients with cirrhosis. Evaluation of MHE could help predict
      survival times and outcomes of patients with specific MELD scores. The CFF could
      help physicians determine prognoses of patients with cirrhosis.

PMID- 26299415
TI  - Preparation of enantiomerically pure open calcocene and strontocene complexes and
      their application in ring opening polymerizations of rac-lactide.
AB  - The synthesis of C2 symmetric enantiomerically pure open Ca and Sr metallocenes,
      [(eta(5)-pdl*)2Ca(thf)] (1) and [(eta(5)-pdl*)2Sr(thf)2] (2) (pdl* =
      dimethylnopadienyl) is described and these complexes were fully characterized.
      The solid state structures confirm that the pdl* ligands coordinate exclusively
      with the less sterically demanding site to the Ca and Sr atoms. These complexes
      are active catalysts for the controlled ring opening polymerization (ROP) of rac
      lactide to give heterotactically enriched polylactides (PL) with narrow
      polydispersities (PDI = 1.29-1.31) and without adding further activators.

PMID- 26299414
TI  - Outcomes and Factors Associated With Reduced Symptoms in Patients With
      Gastroparesis.
AB  - BACKGROUND & AIMS: Gastroparesis is a chronic clinical syndrome characterized by
      delayed gastric emptying. However, little is known about patient outcomes or
      factors associated with reduction of symptoms. METHODS: We studied adult patients
      with gastroparesis (of diabetic or idiopathic type) enrolled in the National
      Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical
      Research Consortium Gastroparesis Registry, seen every 16 weeks and treated
      according to the standard of care with prescribed medications or other therapies
      at 7 tertiary care centers. Characteristics associated with reduced symptoms,
      based on a decrease of 1 or more in the gastroparesis cardinal symptom index
      (GCSI) score after 48 weeks of care, were determined from logistic regression
      models. Data were collected from patients for up to 4 years (median, 2.1 y).
      RESULTS: Of 262 patients, 28% had reductions in GCSI scores of 1 or more at 48
      weeks. However, there were no significant reductions in GCSI score from weeks 48
      through 192. Factors independently associated with reduced symptoms at 48 weeks
      included male sex, age 50 years and older, initial infectious prodrome,
      antidepressant use, and 4-hour gastric retention greater than 20%. Factors
      associated with no reduction in symptoms included overweight or obesity, a
      history of smoking, use of pain modulators, moderate to severe abdominal pain, a
      severe gastroesophageal reflex, and moderate to severe depression. CONCLUSIONS:
      Over a median follow-up period of 2.1 years, 28% of patients treated for
      gastroparesis at centers of expertise had reductions in GCSI scores of 1 or
      greater, regardless of diabetes. These findings indicate the chronic nature of
      gastroparesis. We identified factors associated with reduced symptoms that might
      be used to guide treatment. ClinicalTrials.gov no: NCT00398801.

PMID- 26299417
TI  - Amniocentesis vs chorionic villous sampling as a diagnostic test after an
      abnormal noninvasive prenatal testing result.

PMID- 26299416
TI  - Multimodal nociceptive mechanisms underlying chronic pelvic pain.
AB  - OBJECTIVE: We sought to evaluate candidate mechanisms underlying the pelvic floor
      dysfunction in women with chronic pelvic pain (CPP) and/or painful bladder
      syndrome (PBS)/interstitial cystitis. Notably, prior studies have not
      consistently controlled for potential confounding by psychological or anatomical
      factors. STUDY DESIGN: As part of a larger study on pelvic floor pain dysfunction
      and bladder pain sensitivity, we compared a measure of mechanical pain
      sensitivity, pressure pain thresholds (PPTs), between women with pelvic pain and
      pain-free controls. We also assessed a novel pain measure using degree and
      duration of postexam pain aftersensation, and conducted structural and functional
      assessments of the pelvic floor to account for any potential confounding.
      Phenotypic specificity of pelvic floor measures was assessed with receiver
      operator characteristic curves adjusted for prevalence. RESULTS: A total of 23
      women with CPP, 23 women with PBS, and 42 pain-free controls completed the study.
      Women with CPP or PBS exhibited enhanced pain sensitivity with lower PPTs (1.18
      [interquartile range, 0.87-1.41] kg/cm(2)) than pain-free participants (1.48
      [1.11-1.76] kg/cm(2); P < .001) and prolonged pain aftersensation (3.5 [0-9] vs 0
      [0-1] minutes; P < .001). Although genital hiatus (P < .01) was wider in women
      with CPP there were no consistently observed group differences in pelvic floor
      anatomy, muscle tone, or strength. The combination of PPTs and aftersensation
      duration correlated with severity of pelvic floor tenderness (R(2), 41-51; P <
      .01). Even after adjustment for prevalence, the combined metrics discriminated
      pain-free controls from women with CPP or PBS (area under the curve, 0.87).
      CONCLUSION: Both experimental assessment of pelvic floor pain thresholds and
      measurement of sustained pain are independently associated with pelvic pain
      phenotypes. These findings suggest systematic clinical assessment of the time
      course of provoked pain symptoms, which occurs over seconds for mechanical pain
      thresholds vs minutes for aftersensation pain, would be helpful in identifying
      the fundamental mechanisms of pelvic floor pain. Longitudinal studies of
      therapies differentially targeting these discrete mechanisms are needed to
      confirm their clinical significance.

PMID- 26299418
TI  - Filtration system performance cleaning exhaust air of pneumatic maize seed
      drills.
AB  - BACKGROUND: In the agricultural sector, toxic substances can be released into the
      atmosphere. In recent years, Europe has encountered a significant environmental
      issue related to the dispersion of pesticides during maize seeding, especially
      when performed with pneumatic seed drills. This phenomenon can be very dangerous
      for insects, as the dispersed dust contains pesticides (insecticides, fungicides,
      etc.) used to dress maize seeds. On the basis of these considerations,
      experimental tests have been carried out using a filtration system to clean the
      airflow that exits from the fan of pneumatic maize seed drills. RESULTS: The
      tested filtration system does not interfere with the seeding quality because the
      vacuum level observed within the filtration system assembled on the seeder (5.7
      kPa) is 27% higher than the correct vacuum level to guarantee good seeding
      quality (4.2 kPa). In addition, it enables a reduction in the risk of
      environmental contamination, as no dust deposits were found at different
      distances from the machine. CONCLUSION: The use of a filtration system shows
      advantages in terms of environmental and operator safety because dangerous
      materials are contained in the filter case, thus avoiding contamination of
      neighbouring areas and the machinery used (tractor and seed drill). (c) 2015
      Society of Chemical Industry.

PMID- 26299419
TI  - Quantitative measurements in capsule endoscopy.
AB  - This review summarizes several approaches for quantitative measurement in capsule
      endoscopy. Video capsule endoscopy (VCE) typically provides wireless imaging of
      small bowel. Currently, a variety of quantitative measurements are implemented in
      commercially available hardware/software. The majority is proprietary and hence
      undisclosed algorithms. Measurement of amount of luminal contamination allows
      calculating scores from whole VCE studies. Other scores express the severity of
      small bowel lesions in Crohn's disease or the degree of villous atrophy in celiac
      disease. Image processing with numerous algorithms of textural and color feature
      extraction is further in the research focuses for automated image analysis. These
      tools aim to select single images with relevant lesions as blood, ulcers, polyps
      and tumors or to omit images showing only luminal contamination. Analysis of
      motility pattern, size measurement and determination of capsule localization are
      additional topics. Non-visual wireless capsules transmitting data acquired with
      specific sensors from the gastrointestinal (GI) tract are available for clinical
      routine. This includes pH measurement in the esophagus for the diagnosis of acid
      gastro-esophageal reflux. A wireless motility capsule provides GI motility
      analysis on the basis of pH, pressure, and temperature measurement.
      Electromagnetically tracking of another motility capsule allows visualization of
      motility. However, measurement of substances by GI capsules is of great interest
      but still at an early stage of development. 

PMID- 26299420
TI  - Reflectance confocal microscopy for plaque psoriasis therapeutic follow-up during
      an anti-TNF-alpha monoclonal antibody: an observational multicenter study.
AB  - BACKGROUND: Psoriasis is a chronic recurrent inflammatory skin disease that
      affects 2-3% of the world population. Biologics are relatively new systemic
      treatments that block molecular steps important in the pathogenesis of psoriasis.
      In vivo Reflectance confocal microscopy (RCM) is a non-invasive, imaging
      technique already reported to be useful in the evaluation of the follow-up of PP
      under treatment with topical actives and phototherapy. No reports on systemic
      treatments have been proposed in literature so far. OBJECTIVE: The aim of this
      study was to evaluate the feasibility of RCM in the monitoring of microscopic
      response to a subcutaneous anti-TNF treatment, Adalimumab. METHODS: One target
      lesion with typical clinical aspect, from 48 psoriatic patients, was evaluated
      using RCM at baseline, after 4 and 8 weeks of treatment. RESULTS: Microscopic
      confocal changes were followed up during treatment. Results disclosed
      identification of early microscopic evidence of the anti-inflammatory activity of
      Adalimumab not detected at clinical examination. Confocal feature related to the
      effect of TNF-alpha on melanocytes activity has been also identified. CONCLUSION:
      Early detected RCM parameters related to Adalimumab activity could be used to
      identify an early response to the treatment. RCM seems to be able to give useful
      and practical information about follow-up in patients with PP under treatment
      with Adalimumab.

PMID- 26299421
TI  - Epidemiological studies of neurological signs and symptoms and blood pressure in
      populations near the industrial methylmercury contamination at Minamata, Japan.
AB  - Severe methylmercury exposure occurred in Minamata, Japan. Only a limited number
      of epidemiological studies related to that exposure have been carried out. The
      evidence that methylmercury is cardiotoxic is very limited, and these studies
      provide only minimal support for that hypothesis. We therefore analyzed the data
      both from an investigation in Minamata and neighboring communities in 1971 and an
      investigation in 1974 in another area simultaneously. We included a total of
      3,751 participants. We examined the association of residential area with
      neurological signs or blood pressure using logistic regression or multiple linear
      regression models, adjusting for sex and age. We found that the prevalence of
      neurological signs and symptoms was elevated in the Minamata area (high
      exposure), followed by the Goshonoura area (medium-exposure). Moreover, blood
      pressure was elevated in residents of the Minamata area.

PMID- 26299422
TI  - Dichotic listening and attention: the legacy of Phil Bryden.
AB  - In this article I review the early auditory laterality and dichotic listening
      research from the perspective of the legacy of Phil Bryden's pioneering
      contributions to not only empirical work, but also on theory, critical
      interpretations of results, and statistical issues, with a focus on the role of
      attention. In doing so, I am describing how my own research was shaped and
      influenced by Phil Bryden and his work on auditory laterality and dichotic
      listening. In addition to personal recollections of my meetings and discussions
      with Phil that had a profound impact on my later career, I have focused the
      overview on Phil's early dichotic listening papers from the 1960s, to be followed
      by a detailed review and discussion of the seminal [Bryden, M. P., Munhall, K., &
      Allard, F. (1983). Attentional biases and the right-ear effect in dichotic
      listening. Brain and Language, 18, 236-248] paper on attentional effects on the
      ear advantage in dichotic listening. Finally, I review the little known fact that
      Phil was also a contributor to the very first functional neuroimaging study that
      used dichotic stimuli.

PMID- 26299423
TI  - Kinship reinforces cooperative predator inspection in a cichlid fish.
AB  - Kin selection theory predicts that cooperation is facilitated between genetic
      relatives, as by cooperating with kin an individual might increase its inclusive
      fitness. Although numerous theoretical papers support Hamilton's inclusive
      fitness theory, experimental evidence is still underrepresented, in particular in
      noncooperative breeders. Cooperative predator inspection is one of the most
      intriguing antipredator strategies, as it implies high costs on inspectors.
      During an inspection event, one or more individuals leave the safety of a group
      and approach a potential predator to gather information about the current
      predation risk. We investigated the effect of genetic relatedness on cooperative
      predator inspection in juveniles of the cichlid fish Pelvicachromis taeniatus, a
      species in which juveniles live in shoals under natural conditions. We show that
      relatedness significantly influenced predator inspection behaviour with kin dyads
      being significantly more cooperative. Thus, our results indicate a higher
      disposition for cooperative antipredator behaviour among kin as predicted by kin
      selection theory. 

PMID- 26299424
TI  - Absorption and metabolism characteristics of pristimerin as determined by a
      sensitive and reliable LC-MS/MS method.
AB  - In this research, a sensitive and reliable LC-MS/MS method was developed and
      applied to determine the concentration of pristimerin in rat plasma, cell
      incubation media and metabolism incubation mixtures. The absolute oral
      bioavailability of pristimerin is 28.4% at a dose of 1 mg.kg(-1), and the
      bioavailability was poor. The bidirectional transport of pristimerin across Caco
      2 cells was studied in vitro. A markedly higher transport of pristimerin across
      Caco-2 cells was observed in the basolateral-to-apical direction and was
      abrogated in the presence of the P-gp inhibitor, verapamil. The result indicated
      that P-gp might be involved in the transport of pristimerin in intestine. The
      phase I and phase II metabolic stability was also investigated using human liver
      microsomes (HLM) and S9 fractions, respectively. Pristimerin was stable in S9
      fractions but metabolized in HLM with a half-life of 20.4 min, which indicated
      that pristimerin could be mainly metabolized by phase I enzymes. In conclusion,
      the absolute oral bioavailability of pristimerin in plasma, transport across Caco
      2 cell monolayers, and metabolic stability in HLM and S9 fractions were
      systematically investigated by using a sensitive and reliable LC-MS/MS method.

PMID- 26299425
TI  - Pharmacogenetics of Bisphosphonate-associated Osteonecrosis of the Jaw.
AB  - Osteonecrosis of the jaws (ONJ) is a potentially severe disorder that develops in
      a subgroup of individuals who have used bisphosphonate (BP) medications. Several
      clinical risk factors have been associated with the risk of ONJ development, but
      evidence is limited and in most instances ONJ remains an unpredictable adverse
      drug reaction. Interindividual genetic variability can contribute to explaining
      ONJ development in a subset of BP users and the discovery of relevant associated
      gene variants could lead to the identification of individuals at higher risk. No
      genetic variant has been found to be robustly associated with susceptibility to
      ONJ. 

PMID- 26299426
TI  - Synthesis of microcapsules containing different extractant agents.
AB  - Mercury is one of the most toxic pollutants, with high capacity of accumulation
      in living organism, causing important human health problems. Therefore, the
      mercury removal from water is an important research goal. In a previous work, an
      extractant agent [di(2-ethylhexyl)phosphoric acid] was microencapsulated in
      poly(styrene-co-divinylbenzene) by means of suspension polymerisation using
      toluene as diluent. In this study, this recipe has been modified changing the
      toluene by heptane and extended to four additional extractants (trioctylamine,
      trioctylmethylammonium chloride [TOMAC], tributyl phosphate and trioctylphosphine
      oxide). The polluting potential of the waste liquid from the process was measured
      by total organic carbon and chemical oxygen demand analyses. The morphology,
      particle size and distribution were studied by scanning electron microscopy and
      low angle laser light scattering. The amount of extractant agent into the
      microcapsules and the microencapsulation efficiency were determined by
      thermogravimetric analysis and the mercury removal capacity by equilibrium
      studies. Microcapsules containing TOMAC demonstrated to be the best material for
      the mercury removal and retention. 

PMID- 26299427
TI  - Structural, electronic and optical properties of a hybrid triazine-based
      graphitic carbon nitride and graphene nanocomposite.
AB  - The interfacial effect on the structural, electronic and optical properties of a
      hybrid triazine-based graphitic carbon nitride and graphene nanocomposite is
      calculated using the first-principles method. It reveals the favorable stacking
      pattern utilizing the ab initio thermodynamics approach. The electronic band
      structure presents that the high carrier mobility is maintained in a hybrid g
      CN/G nanocomposite, and a moderate band gap is opened by the interactions between
      g-C3N4 and graphene. Moreover, the opened band gap can be tuned regularly with
      the interfacial distance. Based on the analysis of the imaginary part of
      dielectric function of the graphene, the g-C3N4 monolayer and the hybrid g-CN/G
      nanocomposite, it is found that the hybrid g-CN/G nanocomposite displays enhanced
      and extended optical absorption compared to simplex graphene and the g-C3N4
      monolayer. 

PMID- 26299428
TI  - Peroxisome proliferator-activated receptor-gamma inhibits pancreatic cancer cell
      invasion and metastasis via regulating MMP-2 expression through PTEN.
AB  - The invasive and metastatic behavior of pancreatic cancer is associated with a
      poor prognosis. Therefore, understanding the molecular mechanisms underlying the
      invasion and metastasis of pancreatic cancer has important application values
      theoretically and clinically. In previous years, with increasing studies focusing
      on tumor pathogenesis, it has been revealed that peroxisome proliferator
      activated receptor-gamma (PPARgamma) and phosphatase and tensin homolog (PTEN)
      are closely associated with the occurrence and development of pancreatic cancer.
      Thus, in the present study, a scratch wound assay, western blotting and transwell
      assays were used to investigate their function. The scratch wound assay
      demonstrated that treatment with the PPARgamma ligand rosiglitazone (RGZ) could
      reduce the movement and migration of pancreatic cancer cells. Western blotting
      results indicated that while RGZ inhibited the expression of matrix
      metalloproteinase (MMP)-2, PPARgamma inhibitors promoted MMP-2 expression.
      However, PPARgamma ligands and inhibitors did not affect the expression of MMP-9.
      Further investigation indicated that the regulation of MMP-2 by PPARgamma
      activation occurred through PTEN. In addition, PPARgamma activation promoted PTEN
      expression, thereby inhibiting the expression of MMP-2. Subsequent transwell
      experiments demonstrated that RGZ treatment significantly inhibited the
      invasiveness of pancreatic cancer cells and the inhibitory effect of RGZ was
      completely reversed by simultaneous transfection of the MMP-2-overexpressing
      vector, which increased the invasiveness of pancreatic cancer cells. Therefore,
      PPARgamma activation can activate PTEN expression, thereby suppressing the
      expression of MMP-2 and hence inhibiting the invasion and metastasis of
      pancreatic cancer cells.

PMID- 26299429
TI  - Rapid quantification of starch molecular order through multivariate modelling of
      (13)C CP/MAS NMR spectra.
AB  - A partial least squares model has been generated enabling the rapid assessment of
      ordered molecular structure in a semi-crystalline polymer, starch, directly from
      solid state NMR spectra. Solid state NMR spectroscopy offers many advantages over
      conventional analysis tools being non-destructive and functional in complex
      mixtures. 

PMID- 26299430
TI  - A dual optical and nuclear imaging reagent for peptide labelling via disulfide
      bridging.
AB  - We report a concise approach to a multimodal imaging reagent for peptide
      labelling via disulfide bridging. The reagent is constructed using a one pot,
      three component, [3 + 2] cycloaddition of a fluorescent azide with a
      dithiomaleimide-alkyne, with concomitant incorporation of (125)I. The
      dithiomaleimide handle then enables site selective conjugation to a disulfide
      bond of a peptide whilst retaining the key structural bridging functionality, as
      exemplified on the therapeutic peptide octreotide. 

PMID- 26299431
TI  - Structural Adaptability Facilitates Histidine Heme Ligation in a Cytochrome P450.
AB  - Almost all known members of the cytochrome P450 (CYP) superfamily conserve a key
      cysteine residue that coordinates the heme iron. Although mutation of this
      residue abolishes monooxygenase activity, recent work has shown that mutation to
      either serine or histidine unlocks non-natural carbene- and nitrene-transfer
      activities. Here we present the first crystal structure of a histidine-ligated
      P450. The T213A/C317H variant of the thermostable CYP119 from Sulfolobus
      acidocaldarius maintains heme iron coordination through the introduced ligand, an
      interaction that is accompanied by large changes in the overall protein
      structure. We also find that the axial cysteine C317 may be substituted with any
      other amino acid without abrogating folding and heme cofactor incorporation.
      Several of the axial mutants display unusual spectral features, suggesting that
      they have active sites with unique steric and electronic properties. These novel,
      highly stable enzyme active sites will be fruitful starting points for
      investigations of non-natural P450 catalysis and mechanisms. 

PMID- 26299432
TI  - Regional Isolation Drives Bacterial Diversification within Cystic Fibrosis Lungs.
AB  - Bacterial lineages that chronically infect cystic fibrosis (CF) patients
      genetically diversify during infection. However, the mechanisms driving
      diversification are unknown. By dissecting ten CF lung pairs and studying ~12,000
      regional isolates, we were able to investigate whether clonally related
      Pseudomonas aeruginosa inhabiting different lung regions evolve independently and
      differ functionally. Phylogenetic analysis of genome sequences showed that
      regional isolation of P. aeruginosa drives divergent evolution. We investigated
      the consequences of regional evolution by studying isolates from mildly and
      severely diseased lung regions and found evolved differences in bacterial
      nutritional requirements, host defense and antibiotic resistance, and virulence
      due to hyperactivity of the type 3 secretion system. These findings suggest that
      bacterial intermixing is limited in CF lungs and that regional selective
      pressures may markedly differ. The findings also may explain how specialized
      bacterial variants arise during infection and raise the possibility that pathogen
      diversification occurs in other chronic infections characterized by spatially
      heterogeneous conditions. 

PMID- 26299434
TI  - Cytokine-induced killer cells induce apoptosis and inhibit the Akt/nuclear factor
      kappaB signaling pathway in cisplatin-resistant human glioma U87MG cells.
AB  - Despite advances in the development of treatment methods, glioma remains among
      the cancer types with a high rate of mortality. Therefore, significant efforts
      are made to develop novel strategies for the treatment of glioma. Ineffective,
      long-term cancer chemotherapy can lead to multidrug resistance (MDR), which is
      one of the most common reasons for the failure of chemotherapy. The present study
      investigated the effects of cytokine-induced killer cells (CIK) on reversing MDR
      in cisplatin-resistant U87MG cells (U87MG/DDP). Mononuclear cells were isolated
      from the peripheral blood of healthy individuals and cultured in vitro in the
      presence of a combination of cytokines to generate CIK for the treatment of
      U87MG/DDP. An MTS assay, flow cytometric analysis of apoptosis, ELISA, western
      blotting and reverse transcription quantitative polymerase chain reaction were
      used to investigate the MDR-reversing effects of CIK as well as the underlying
      mechanisms. The results showed that cisplatin sensitivity and the apoptotic rate
      following cisplatin treatment were increased, P-glycoprotein expression was
      decreased and the intracellular rhodamine-123 content was increased in U87MG/DDP
      co-cultured with CIK. In addition, the present study also identified increased
      mRNA and protein expression levels of MDR gene 1 (MDR1), MDR-associated protein 1
      (MRP1), B-cell lymphoma 2, Survivin and glutathione S-transferase-pi, while the
      phosphorylation of AKT and the transcriptional activity of nuclear factor-kappaB
      in CIK co-cultured U87MG/DDP was decreased. These results indicated that pre
      treatment with CIK reversed the MDR of U87MG/DDP, and that CIK-induced apoptosis
      of U87MG/DDP was associated with the inhibition of Akt/NF-kappaB. These findings
      suggested that treatment with CIK may be an effective method to enhance the
      sensitivity of patients with glioma to chemotherapy.

PMID- 26299435
TI  - Probing Rotational Motion in 4-tert-Butylcatechol through H Atom
      Photofragmentation: Deviations from Axial Recoil.
AB  - The time-resolved photofragmentation dynamics of 4-tert-butylcatechol were
      studied following one photon excitation to the S1 (1(1)pipi*) state with
      ultraviolet radiation in the range 260 <= lambda <= 286 nm. The preparation of an
      aligned molecular ensemble via photoexcitation leads to anisotropy in the H atom
      photofragments. These H atoms originate from the decay of the S1 state through
      coupling onto the S2 ((1)pisigma*) state, which is dissociative along the
      nonintramolecular hydrogen bonded "free" O-H bond. The degree of anisotropy of
      these photogenerated H atoms decreases with increasing pump-probe time delay.
      This is attributed to rotational dephasing of the initially aligned molecular
      ensemble. The measured dephasing occurs on a time scale akin to the appearance
      time of these H atoms, which likely places an intrinsic lower bound on the
      dephasing lifetime. The present work demonstrates how a careful balance between
      the appearance time of the H atoms, determined by the S1 lifetime, and the
      rotational dephasing in 4-tert-butylcatechol provides an opportune window to
      probe rotational motion in real time. 

PMID- 26299433
TI  - Polyamine biosynthesis is critical for growth and differentiation of the
      pancreas.
AB  - The pancreas, in most studied vertebrates, is a compound organ with both exocrine
      and endocrine functions. The exocrine compartment makes and secretes digestive
      enzymes, while the endocrine compartment, organized into islets of Langerhans,
      produces hormones that regulate blood glucose. High concentrations of polyamines,
      which are aliphatic amines, are reported in exocrine and endocrine cells, with
      insulin-producing beta cells showing the highest concentrations. We utilized
      zebrafish as a model organism, together with pharmacological inhibition or
      genetic manipulation, to determine how polyamine biosynthesis functions in
      pancreatic organogenesis. We identified that inhibition of polyamine biosynthesis
      reduces exocrine pancreas and beta cell mass, and that these reductions are at
      the level of differentiation. Moreover, we demonstrate that inhibition of
      ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine
      biosynthesis, phenocopies inhibition or knockdown of the enzyme deoxyhypusine
      synthase (DHS). These data identify that the pancreatic requirement for polyamine
      biosynthesis is largely mediated through a requirement for spermidine for the
      downstream posttranslational modification of eIF5A by its enzymatic activator
      DHS, which in turn impacts mRNA translation. Altogether, we have uncovered a role
      for polyamine biosynthesis in pancreatic organogenesis and identified that it may
      be possible to exploit polyamine biosynthesis to manipulate pancreatic cell
      differentiation. 

PMID- 26299436
TI  - The Role of Psychological Factors in Persistent Pain After Cesarean Delivery.
AB  - This French multicenter prospective cohort study recruited 391 patients to
      investigate the risk factors for persistent pain after elective cesarean
      delivery, focusing on psychosocial aspects adjusted for other known medical
      factors. Perioperative data were collected and specialized questionnaires were
      completed to assess reports of pain at the site of surgery. Three dependent
      outcomes were considered: pain at the third month after surgery (M3, n = 268;
      risk = 28%), pain at the sixth month after surgery (M6, n = 239; risk = 19%), and
      the cumulative incidence (up to M6) of neuropathic pain, as assessed using the
      Douleur Neuropathique 4 questionnaire (n = 218; risk = 24.5%). The neuropathic
      aspect of reported pain changed over time in more than 60% of cases, pain being
      more intense if associated with neuropathic features. Whatever the dependent
      outcome, a high mental component of quality of life (SF-36) was protective. Pain
      at M3 was also predicted by pain reported during current pregnancy and a history
      of miscarriage. Pain at M6 was also predicted by report of a postoperative
      complication. Incident neuropathic pain was predicted by pain reported during
      current pregnancy, a previous history of a peripheral neuropathic event, and
      preoperative anxiety. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00812734.
      PERSPECTIVE: Persistent pain after cesarean delivery has a relatively frequent
      neuropathic aspect but this is less stable than that after other surgeries. When
      comparing the risk factor analyses with published data for hysterectomy, the
      influence of preoperative psychological factors seems less important, possibly
      because of the different context and environment.

PMID- 26299437
TI  - Hydrophilic modification of titania nanomaterials as a biofunctional adsorbent
      for selective enrichment of phosphopeptides.
AB  - TiO2-based metal oxide affinity chromatography (MOAC) nanomaterials show high
      potential in phosphoproteome mass-spectrometric (MS) analysis. However, a
      drawback of TiO2 nanomaterials is poor water solubility, which greatly reduces
      the enrichment efficiency of phosphopeptides and eventually limits their use in
      phosphoproteome MS analysis. In this work, a hydrophilic TiO2 hybrid material
      (denoted as NH2@TiO2) is successfully designed with 1,6-hexanediamine modified on
      the surface of TiO2 nanoparticles and applied as a biofunctional adsorbent for
      selective enrichment of phosphopeptides. The novel TiO2 hybrid material with high
      hydrophilicity and biocompatibility is characterized using scanning electron
      microscopy (SEM), energy dispersive X-ray (EDX) and infrared (IR) spectroscopy,
      and its performance in selective enrichment of phosphopeptides is evaluated with
      the standard protein digests, human serum and the tryptic digests of nonfat milk.

PMID- 26299438
TI  - A Preliminary Investigation into Worry about Mental Health: Development of the
      Mental Health Anxiety Inventory.
AB  - BACKGROUND: Worry about physical health is broadly referred to as health anxiety
      and can range from mild concern to severe or persistent anxiety such as that
      found in DSM-IV hypochondriasis. While much is known about anxiety regarding
      physical health, little is known about anxiety regarding mental health. However,
      recent conceptualizations of health anxiety propose that individuals can
      experience severe and problematic worry about mental health in similar ways to
      how people experience extreme worry about physical health. AIMS: Given the
      paucity of research in this area, the aim of the current study was to explore
      anxiety regarding mental health through validation of the Mental Health Anxiety
      Inventory (MHAI), a modified version of the Short Health Anxiety Inventory.
      METHOD: The MHAI, and measures of state anxiety (Depression, Anxiety and Stress
      Scales-21), trait worry (Penn State Worry Questionnaire), and health anxiety
      (Short Health Anxiety Inventory) were administered to 104 adult volunteers from
      the general community. RESULTS: The MHAI demonstrated high internal consistency,
      acceptable test-retest reliability, and good construct validity when correlated
      with other measures of anxiety. Results also indicated that participants worried
      about their mental health and physical health equally, and that almost 9% of
      participants reported levels of mental health anxiety that were potentially
      problematic. CONCLUSION: Preliminary results suggest that a small proportion of
      adults in the community may experience high levels of mental health anxiety
      requiring treatment, and that the MHAI, if validated further, could be a useful
      tool for assessing this form of anxiety.

PMID- 26299439
TI  - Pathway-Based Genome-wide Association Studies Reveal That the Rac1 Pathway Is
      Associated with Plasma Adiponectin Levels.
AB  - Pathway-based analysis as an alternative and effective approach to identify
      disease-related genes or loci has been verified. To decipher the genetic
      background of plasma adiponectin levels, we performed genome wide pathway-based
      association studies in extremely obese individuals and normal-weight controls.
      The modified Gene Set Enrichment Algorithm (GSEA) was used to perform the pathway
      based analyses (the GenGen Program) in 746 European American females, which were
      collected from our previous GWAS in extremely obese (BMI > 35 kg/m(2)) and never
      overweight (BMI<25 kg/m(2)) controls. Rac1 cell motility signaling pathway was
      associated with plasma adiponectin after false-discovery rate (FDR) correction
      (empirical P < 0.001, FDR = 0.008, family-wise error rate = 0.008). Other several
      Rac1-centered pathways, such as cdc42racPathway (empirical P < 0.001), hsa00603
      (empirical P = 0.003) were among the top associations. The RAC1 pathway
      association was replicated by the ICSNPathway method, yielded a FDR = 0.002.
      Quantitative pathway analyses yielded similar results (empirical P = 0.001) for
      the Rac1 pathway, although it failed to pass the multiple test correction (FDR =
      0.11). We further replicated our pathway associations in the ADIPOGen Consortium
      data by the GSA-SNP method. Our results suggest that Rac1 and related cell
      motility pathways might be associated with plasma adiponectin levels and
      biological functions of adiponectin. 

PMID- 26299440
TI  - TIMP3 Attenuates the Loss of Neural Stem Cells, Mature Neurons and Neurocognitive
      Dysfunction in Traumatic Brain Injury.
AB  - Mesenchymal stem cells (MSCs) have been shown to have potent therapeutic effects
      in a number of disorders including traumatic brain injury (TBI). However, the
      molecular mechanism(s) underlying these protective effects are largely unknown.
      Herein we demonstrate that tissue inhibitor of matrix metalloproteinase-3
      (TIMP3), a soluble protein released by MSCs, is neuroprotective and enhances
      neuronal survival and neurite outgrowth in vitro. In vivo in a murine model of
      TBI, intravenous recombinant TIMP3 enhances dendritic outgrowth and abrogates
      loss of hippocampal neural stem cells and mature neurons. Mechanistically we
      demonstrate in vitro and in vivo that TIMP3-mediated neuroprotection is
      critically dependent on activation of the Akt-mTORC1 pathway. In support of the
      neuroprotective effect of TIMP3, we find that intravenous delivery of recombinant
      TIMP3 attenuates deficits in hippocampal-dependent neurocognition. Taken
      together, our data strongly suggest that TIMP3 has direct neuroprotective effects
      that can mitigate the deleterious effects associated with TBI, an area with few
      if any therapeutic options.

PMID- 26299441
TI  - Mixed COPD-asthma Phenotype: ACOS or CAOS? A Reflection on Recent Guidelines and
      Recommendations.

PMID- 26299442
TI  - Experimental adaptation to marine conditions by a freshwater alga.
AB  - The marine-freshwater boundary has been suggested as one of the most difficult to
      cross for organisms. Salt is a major ecological factor and provides an unequalled
      range of ecological opportunity because marine habitats are much more extensive
      than freshwater habitats, and because salt strongly affects the structure of
      microbial communities. We exposed experimental populations of the freshwater alga
      Chlamydomonas reinhardtii to steadily increasing concentrations of salt. About
      98% of the lines went extinct. The ones that survived now thrive in growth medium
      with 36 g?L(-1) NaCl, and in seawater. Our results indicate that adaptation to
      marine conditions proceeded first through genetic assimilation of an inducible
      response to relatively low salt concentrations that was present in the ancestors,
      and subsequently by the evolution of an enhanced inducible response to high salt
      concentrations. These changes appear to have evolved through reversible and
      irreversible modifications, respectively. The evolution of marine from freshwater
      lineages is an example that clearly indicates the possibility of studying certain
      aspects of major ecological transitions in the laboratory.

PMID- 26299444
TI  - Highly Magneto-Responsive Elastomeric Films Created by a Two-Step Fabrication
      Process.
AB  - An innovative method for the preparation of elastomeric magnetic films with
      increased magneto-responsivity is presented. Polymeric films containing aligned
      magnetic microchains throughout their thickness are formed upon the
      magnetophoretic transport and assembly of microparticles during polymer curing.
      The obtained films are subsequently magnetized at a high magnetic field of 3 T
      directed parallel to the orientation of the microchains. We prove that the
      combination of both alignment of the particles along a favorable direction during
      curing and the subsequent magnetization of the solid films induces an impressive
      increase of the films' deflection. Specifically, the displacements reach few
      millimeters, up to 85 times higher than those of the nontreated films with the
      same particle concentration. Such a process can improve the performance of the
      magnetic films without increasing the amount of magnetic fillers and, thus,
      without compromising the mechanical properties of the resulting composites. The
      proposed method can be used for the fabrication of magnetic films suitable as
      components in systems in which large displacements at relatively low magnetic
      fields are required, such as sensors and drug delivery or microfluidic systems,
      especially where remote control of valves is requested to achieve appropriate
      flow and mixing of liquids. 

PMID- 26299443
TI  - Studies on ageing and the severity of radiographic joint damage in rheumatoid
      arthritis.
AB  - INTRODUCTION: The western population is ageing. It is unknown whether age at
      diagnosis affects the severity of Rheumatoid Arthritis (RA), we therefore
      performed the present study. METHOD: 1,875 RA-patients (7,219 radiographs)
      included in five European and North-American cohorts (Leiden-EAC, Wichita, Umea,
      Groningen and Lund) were studied on associations between age at diagnosis and
      joint damage severity. In 698 Leiden RA-patients with 7-years follow-up it was
      explored if symptom duration, anti-citrullinated-peptide-antibodies (ACPA),
      swollen joint count (SJC) and C-reactive-protein (CRP) mediated the association
      of age with joint damage. Fifty-six other RA-patients of the EAC-cohort underwent
      baseline MRIs of wrist, MCP and MTP-joints; MRI-inflammation (RAMRIS-synovitis
      plus bone marrow edema) was also evaluated in mediation analyses. Linear
      regression and multivariate normal regression models were used. RESULTS: Analysis
      on the five cohorts and the Leiden-EAC separately revealed 1.026-fold and 1.034
      fold increase of radiographic joint damage per year increase in age (beta=1.026,
      1.034, both p<0.001); this effect was present at baseline and persisted over
      time. Age correlated stronger with baseline erosion-scores compared to joint
      space narrowing (JSN)-scores (r=0.38 versus 0.29). Symptom duration, ACPA, SJC
      and CRP did not mediate the association of age with joint damage severity. Age
      was significantly associated with the MRI-inflammation-score after adjusting for
      CRP and SJC (beta=1.018, p=0.027). The association of age with joint damage
      (beta=1.032, p=0.004) decreased after also including the MRI-inflammation-score
      (beta=1.025, p=0.021), suggesting partial mediation. CONCLUSION: RA-patients
      presenting at higher age have more severe joint damage; this might be partially
      explained by more severe MRI-detected inflammation at higher age.

PMID- 26299445
TI  - Granulomatous variant of vegetative pyoderma gangrenosum with
      sternocostoclavicular hyperostosis.

PMID- 26299446
TI  - Amyloid Goiter in a Patient with Progressive Thyromegaly.

PMID- 26299447
TI  - Electrical detection of ortho-para conversion in fullerene-encapsulated water.
AB  - Water exists in two spin isomers, ortho and para, that have different nuclear
      spin states. In bulk water, rapid proton exchange and hindered molecular rotation
      obscure the direct observation of two spin isomers. The supramolecular
      endofullerene H2O@C60 provides freely rotating, isolated water molecules even at
      cryogenic temperatures. Here we show that the bulk dielectric constant of this
      substance depends on the ortho/para ratio, and changes slowly in time after a
      sudden temperature jump, due to nuclear spin conversion. The attribution of the
      effect to ortho-para conversion is validated by comparison with nuclear magnetic
      resonance and quantum theory. The change in dielectric constant is consistent
      with an electric dipole moment of 0.51+/-0.05 Debye for an encapsulated water
      molecule, indicating the partial shielding of the water dipole by the
      encapsulating cage. The dependence of bulk dielectric constant on nuclear spin
      isomer composition appears to be a previously unreported physical phenomenon. 

PMID- 26299448
TI  - Pay Now or Pay Later: An Economic Rationale for State-Funded Helping Services to
      Assist Women Leaving an Abusive Relationship.
AB  - There has been an increase in costing analysis of intimate partner violence in
      recent decades, including the monetary impact to government, society, and the
      individual. Using data collected in a Canadian longitudinal study, the empirical
      analysis in this article provides an economic rationale for mobilizing public
      resources that improve the well-being of women leaving an abusive relationship. I
      estimated six variants of a selection model and used a costing exercise to build
      an economic case for preventive and other helping services to support women over
      their healing journey. The removal of financial constraints suffered by abused
      women, in support of their training needs, as well as reduced barriers to
      preventive health care services, may potentially lead to fiscal resource savings
      in the long run. 

PMID- 26299449
TI  - Approaches of intensive care nurses towards sensory requirements of patients.
AB  - AIMS AND OBJECTIVES: This study aimed to identify the approaches used by nurses
      to address the sensory requirements of patients to respond to the concerns and
      needs in this area. BACKGROUND: Preventing sensory problems is very important for
      intensive care nurses as these problems may cause various additional health
      problems in intensive care patients; however, no study has evaluated the
      approaches used by nurses in this respect. DESIGN: The study was conducted as a
      descriptive study in all internal medicine intensive care units at hospitals
      located within the borders of the metropolitan municipality in the capital city
      of Turkey. METHOD: Data were collected using case forms that were developed
      through expert opinions to identify the approaches of nurses for the sensory
      requirements of patients. The study was conducted with 95 nurses who agreed to be
      involved in the study of the 107 internal medicine intensive care nurses in the
      research population. RESULTS: Most of the nurses (86.3%) who took part in this
      study indicated that intensive care patients had sensory requirements, but 80%
      clarified that their priority was to maintain life support and to meet their
      physiological needs. Almost all of the nurses were able to accurately identify
      the specific sensory problems of the six different ones in cases that were
      assigned to them. However, this ratio decreased when identifying the proper
      approach for the given sensory requirement. CONCLUSIONS: Nurses were able to
      identify sensory requirements of patients, but they do need support in deciding
      the appropriate management approach. This study may fill the gap in the
      literature regarding the approaches of nurses towards sensory requirements and to
      provide contribution for future research. RELEVANCE TO CLINICAL PRACTICE: To help
      intensive care patients with sensory problems, nurses should routinely assess
      patients' psychology and should do appropriate interventions.

PMID- 26299450
TI  - Do depressive symptoms predict cancer incidence?: 17-year follow-up of the
      Whitehall II study.
AB  - OBJECTIVE: To explore the association between depressive symptom history and
      cancer incidence. METHODS: Affective/emotional depressive symptoms were assessed
      using the General Health Questionnaire (GHQ-30) depression sub-scale across phase
      1 (1985-1988), phase 2 (1989-1990), and phase 3 (1991-1994) of the Whitehall II
      prospective cohort study; 'chronic'=depressive episode at phase 1, 2 and 3;
      'new'=depressive episode at phase 3 only. Cancer incidence was obtained from the
      National Health Service Central Register with an average follow-up of 15.6 years
      (range 0.08-17.4). The study sample consisted of 6983 participants, aged 35-55
      years at baseline. Results were adjusted for age, sex, socio-economic position,
      health behaviours, health status/conditions, medication, and social support.
      RESULTS: Over a 17.4 year follow-up, chronic depressive symptoms did not increase
      the risk of cancer incidence compared to those who never experienced symptoms
      (hazard ratio (HR)=1.03, 95% confidence interval (CI): 0.71-1.49). Participants
      who experienced new depressive symptoms had an increased risk of cancer incidence
      in the first 9 years of follow-up (HR=1.89, 95% CI: 1.23-2.90) but no increased
      risk in later years (HR=0.84, 95% CI: 0.52-1.35). CONCLUSION: Chronic depressive
      symptoms were not associated with cancer incidence. In contrast, new-onset
      symptoms were associated with a substantially increased risk, possibly due to
      reverse causality.

PMID- 26299451
TI  - Cutaneous melioidosis with unusual histological features.
AB  - Melioidosis is caused by the saprophytic gram-negative bacillus Burkholderia
      pseudomallei, and has varied presentations, with cutaneous manifestations
      occurring in about 13% of cases. The usual histopathological features of
      melioidosis are suppurative to chronic granulomatous inflammation. Recommended
      treatment of melioidosis is sequential use of intravenous followed by oral
      antibiotics for a few months, although oral antibiotics alone can be used in
      primary cutaneous melioidosis. We report a case of cutaneous melioidosis in a
      healthy young man, with the unusual histopathological feature of
      lymphoplasmacytic inflammation, and failing an initial trial of oral antibiotics
      alone. 

PMID- 26299452
TI  - Mitochondrial Respiration Controls Lysosomal Function during Inflammatory T Cell
      Responses.
AB  - The endolysosomal system is critical for the maintenance of cellular homeostasis.
      However, how endolysosomal compartment is regulated by mitochondrial function is
      largely unknown. We have generated a mouse model with defective mitochondrial
      function in CD4(+) T lymphocytes by genetic deletion of the mitochondrial
      transcription factor A (Tfam). Mitochondrial respiration deficiency impairs
      lysosome function, promotes p62 and sphingomyelin accumulation, and disrupts
      endolysosomal trafficking pathways and autophagy, thus linking a primary
      mitochondrial dysfunction to a lysosomal storage disorder. The impaired lysosome
      function in Tfam-deficient cells subverts T cell differentiation toward
      proinflammatory subsets and exacerbates the in vivo inflammatory response.
      Restoration of NAD(+) levels improves lysosome function and corrects the
      inflammatory defects in Tfam-deficient T cells. Our results uncover a mechanism
      by which mitochondria regulate lysosome function to preserve T cell
      differentiation and effector functions, and identify strategies for intervention
      in mitochondrial-related diseases.

PMID- 26299454
TI  - Eventual proapoptotic or anti-apoptotic impact of aberrantly expressed Cx43 and
      Cx26 can depend on ER-alpha overexpression in human endometrioid adenocarcinoma.
AB  - Estrogen receptor (ER) and progesterone receptor (PgR) accumulations lead to
      impairment of gap junctional intercellular communication in endometrial cancer.
      The task of this study was to explore relationships of Cx26 and Cx43 with anti
      apoptotic protein Bcl-xL and proapoptotic agent Bak in ER-alpha and PgR negative
      or variably positive endometrioid adenocarcinomas. Cx26, Cx43, Bak, Bcl-xL, PgR
      and ER-alpha were detected in 78 endometrioid adenocarcinomas with
      immunohistochemistry. There was a remarkable cellular re-distribution of Cx26 and
      Cx43 from normally membranous location in normal endometrium to aberrantly
      cytoplasmic expression in endometrioid adenocarcinomas, thus suggesting the
      decrease of functional membranous gap junctions in the malignancy. Bak failed to
      correlate with Cx43 regardless of either PgR or ER-alpha status of tumors, while
      Bcl-xL positively correlated with Cx43 in ER-alpha positive tumors (p = 0.001, r
      = 0.427) and both PgR positive (p = 0.019, r = 0.312) and negative (p = 0.015, r
      = 0.509) cancers. Similarly, Bcl-xL significantly associated with Cx26 in ER
      alpha positive tumors (p = 0.036, r = 0.267) and both PgR positive (p = 0.026, r
      = 0.297) and negative (p = 0.046, r = 0.429) cancers. On the contrary, Bak
      exclusively correlated with Cx26 only in ER-alpha negative tumors (p = 0.027, r =
      0.551). ER-alpha status of endometrioid adenocarcinomas could restrict eventual
      proapoptotic or anti-apoptotic impact of aberrantly expressed Cx43 and Cx26 in
      these tumors. 

PMID- 26299453
TI  - Interactions between Gut Microbiota, Host Genetics and Diet Modulate the
      Predisposition to Obesity and Metabolic Syndrome.
AB  - Obesity, diabetes, and metabolic syndrome result from complex interactions
      between genetic and environmental factors, including the gut microbiota. To
      dissect these interactions, we utilized three commonly used inbred strains of
      mice-obesity/diabetes-prone C57Bl/6J mice, obesity/diabetes-resistant 129S1/SvImJ
      from Jackson Laboratory, and obesity-prone but diabetes-resistant 129S6/SvEvTac
      from Taconic-plus three derivative lines generated by breeding these strains in a
      new, common environment. Analysis of metabolic parameters and gut microbiota in
      all strains and their environmentally normalized derivatives revealed strong
      interactions between microbiota, diet, breeding site, and metabolic phenotype.
      Strain-dependent and strain-independent correlations were found between specific
      microbiota and phenotypes, some of which could be transferred to germ-free
      recipient animals by fecal transplantation. Environmental reprogramming of
      microbiota resulted in 129S6/SvEvTac becoming obesity resistant. Thus,
      development of obesity/metabolic syndrome is the result of interactions between
      gut microbiota, host genetics, and diet. In permissive genetic backgrounds,
      environmental reprograming of microbiota can ameliorate development of metabolic
      syndrome. 

PMID- 26299455
TI  - Lessons from viruses: Small non-coding RNA meets transcription factors (comment
      on DOI 10.1002/bies.201500060).

PMID- 26299456
TI  - Mitochondria: The Red Queen lies within (comment on DOI 10.1002/bies.201500057).

PMID- 26299457
TI  - Receptor activation with a twist (comment on DOI 10.1002/bies.201500041).

PMID- 26299461
TI  - Risk factors for postoperative depression: A retrospective analysis of 248
      subjects operated on for drug-resistant epilepsy.
AB  - The aim of this retrospective case series analysis was to identify the predictors
      of postoperative depression (PostOp-D) in a sample of 248 subjects with focal
      drug-resistant focal epilepsy. The presence or absence of PostOp-D during a 12
      month follow-up period was the outcome variable. Demographic, neurologic,
      psychiatric characteristics, and antiepileptic therapy were the explanatory
      variables. After preliminary bivariate analysis, a multivariate logistic
      regression model was fitted to identify variables associated with PostOp-D. Sixty
      seven patients (27%) experienced PostOp-D. At multivariate analysis, lifetime
      depression, age at surgery, and levetiracetam (LEV) are positive predictors of
      PostOp-D; carbamazepine (CBZ) and anxiety disorders are protective factors. LEV
      increases the risk for PostOp-D by about half; the relative risk (RR) is 1.48.
      Conversely, CBZ decreases the risk for PostOp-D by about half (RR 0.59). Our
      results suggest that careful psychiatric evaluation and follow-up should be
      recommended for subjects at risk. It is advisable to treat patients with
      depression before surgery. Antiepileptic drugs should be selected carefully when
      patients present with not modifiable risk factors, such as positive personal
      history for depression. 

PMID- 26299462
TI  - Can mixed pure hepatocellular carcinoma and germinoma arise together in the
      brain?
AB  - Intracranial germ-cell tumors (GCTs) represent 10-15% of all pediatric brain
      tumors in East Asia. There is a wide histopathological spectrum of intracranial
      GCTs. Germinomas and nongerminomatous GCTs are the two major classifications. It
      is difficult to distinguish different subtypes of intracranial GCTs based solely
      on imaging studies, however, some tumor markers, such as alpha-fetoprotein or
      beta-human chorionic gonadotropin, are helpful for diagnosis. In this study we
      present the case of a 13-year-old girl with an intracranial mixed GCT containing
      a hepatocellular carcinoma and germinoma without a primary liver tumor. Based on
      this unique pathological diagnosis, a series of treatments were applied,
      including surgery for gross tumor removal, adjuvant radiotherapy, and
      chemotherapy. Long-term follow up indicates fair disease control. 

PMID- 26299463
TI  - The Difficult Ureter: Clinical and Radiographic Characteristics Associated With
      Upper Urinary Tract Access at the Time of Ureteroscopic Stone Treatment.
AB  - OBJECTIVE: To evaluate the association between clinicoradiographic features and
      need for prestenting (PS) because of inability of the ureter to accommodate the
      ureteroscope, or ureteral access sheath, at the time of stone treatment.
      MATERIALS AND METHODS: From 2009 to 2013, 120 consecutive nonstented patients
      underwent ureteroscopic stone treatment with preoperative computerized tomography
      urogram. Acute stone events with obstruction or infection were excluded.
      Preoperative radiographic imaging underwent radiologist review.
      Clinicoradiographic features were characterized, and multivariable logistic
      regression models were used to identify covariates independently associated with
      need for PS. RESULTS: Of the 154 renal units treated, 25 (16%) required PS for
      failed primary access. PS ureters were less likely to have a history of prior
      ipsilateral ureteral stent (4% vs 31%) or surgery (8% vs 36%; P <.05).
      Radiographically, PS ureters had a narrower ureteropelvic junction (4 mm vs 5 mm)
      and were more likely to have <50% ureteral opacification on computerized
      tomography urogram (32% vs 9%; P <.05). On multivariable analysis, prior
      ipsilateral ureteral stent (odds ratio [OR] = 0.11) and stone surgery (OR = 0.15)
      reduced the need for PS; meanwhile, <50% ureteral opacification (OR = 4.41) was
      independently associated with an increased risk of access failure. CONCLUSION: We
      report a 16% incidence of access failure requiring PS at time of ureteroscopy.
      Clinically, there was an 89% and 85% risk reduction in the need for PS with prior
      history of ipsilateral ureteral stent or surgery. Radiographically, there was a
      4.4-fold increased risk of PS with <50% ureteral opacification. Accordingly, our
      findings may assist in counseling and operative management of the difficult
      ureter.

PMID- 26299464
TI  - Rapid Identification of Rectal Multidrug-resistant Escherichia coli Before
      Transrectal Prostate Biopsy.
AB  - OBJECTIVE: To develop and evaluate a rapid multiplex-quantitative polymerase
      chain reaction (qPCR) to identify fecal carriers of multidrug-resistant
      extraintestinal pathogenic Escherichia coli (MDR-ExPEC) clonal groups. METHODS:
      Men presenting for transrectal prostate biopsy (TPB) at the San Diego Veterans
      Affairs Medical Center underwent rectal culture immediately before TPB. Rectal
      swabs were streaked onto ciprofloxacin-supplemented (4 mg/L) MacConkey agar
      plates, identified, and susceptibility tested. The same swab was sent to the
      University of Washington for qPCR test (EST200) targeting 2 major MDR-ExPEC
      clonal groups--ST131 and ST69--that combined were expected to represent majority
      of fluoroquinolone (FQ)- and trimethoprim-sulfamethoxazole-resistant E coli. We
      calculate test characteristics including the area under the receiver operative
      curve (AUC). RESULTS: We enrolled 104 men from 11/5/2013 to 6/10/2014. FQ
      resistant E coli were cultured from 19.2% (20/104) of rectal swabs, and 26%
      (27/104) of all swabs were positive for EST200 by PCR. The test characteristics
      comparing the EST200 to the culture-based detection of FQ resistance were 75%,
      86%, 94%, and 56%, respectively. The AUC was 0.84 for the EST200 to detect FQ
      resistance before TPB. CONCLUSION: Compared to the reference standard rectal
      culture, EST200 was able to detect majority of FQ-resistant E coli on rectal
      swabs before prostate biopsy.

PMID- 26299465
TI  - Analyzing Why Men Seek Treatment for Lower Urinary Tract Symptoms and Factors
      Associated With Nonimprovement.
AB  - OBJECTIVE: To determine the motivating factor for why men seek urologic care and
      determine persistence of these symptoms and any factors that influence
      resolution. METHODS: Men presenting to an outpatient urology clinic with lower
      urinary tract symptoms (LUTSs) were prospectively evaluated. At each of 2 visits,
      surveys were administered including the American Urological Association Symptom
      Index and a chief LUTS complaint (CLC) identification form. On the CLC
      identification form, symptoms were considered "transient" if only seen at V1 and
      "persistent" if they were selected at both visits. RESULTS: Sixty-five percent of
      the 1240 participants were able to specify a CLC. Among these, nocturia was by
      far the most common and was found to be persistent in 49% of cases. When
      comparing the groups of patients who presented with transient verses persistent
      nocturia, older age (P <.001), diabetes (P = .006), hypertension (P = .033),
      alpha-blocker use (P = .018), 5-alpha-reductase inhibitor use (P = .008), higher
      nocturia severity (P <.001), and more severe American Urological Association
      Symptom Index scores at initial visit (P = .047) were found to be predictors of
      persistent nocturia. CONCLUSION: Most men with LUTS can identify a predominant
      CLC. Of these, nocturia is the primary CLC of most men and does not improve in
      almost 50% of those studied. By improving our identification of a predominant CLC
      and the patient factors that influence both the development and persistence of
      urinary symptoms, we may start to better evaluate and hopefully focus treatment
      on the most bothersome urinary symptom.

PMID- 26299466
TI  - Tungsten lamp and chronic actinic dermatitis.
AB  - Chronic actinic dermatitis is often associated with sensitivity to UV light. It
      is not well recognised that chronic actinic dermatitis may be exacerbated by
      light in the visible spectrum. We describe an unusual case of chronic actinic
      dermatitis exacerbated by a tungsten lamp, which emits light in the visible
      spectrum.

PMID- 26299468
TI  - East, West: is home best?

PMID- 26299467
TI  - Longitudinal differences in sleep duration in Hispanic and Caucasian children.
AB  - BACKGROUND AND AIM: Short sleep duration is associated with significant negative
      consequences, including poor school performance, behavioral problems, obesity,
      and hypertension. There is prior evidence that there are disparities in sleep
      duration related to ethnicity; however, there are no specific data on Hispanic
      children. We aimed to test the hypothesis that there are ethnic differences in
      parent-reported sleep duration in a community-based cohort of Hispanic and
      Caucasian children. METHODS: We examined the parent-reported sleep patterns of a
      community-based prospective cohort (Tucson Children's Assessment of Sleep Apnea
      study [TuCASA]) involving 338 Hispanic and Caucasian children at two time points
      approximately five years apart. RESULTS: In the initial phase of the TuCASA study
      with a cohort median age of 8.8 years (interquartile range (IQR), 7.6-10.1
      years), parent-reported sleep duration during weekdays was shorter in Hispanic
      (median, 9.5 h; IQR, 9.0, 10.0 years) than in Caucasian children (10 h; IQR, 9.5,
      10.0 h; p < 0.0001); however, this difference was not seen 5 years later when the
      cohort was older (median age, 13.3 years; IQR, 11.9-14.6 years; p = 0.43). In
      addition, Hispanic children had a significantly later bedtime at both time points
      (p < 0.02). In the initial phase, parent-reported sleep duration during weekends
      tended to be shorter in Hispanic than in Caucasian children (p = 0.06).
      CONCLUSIONS: Short sleep duration in Hispanic children may contribute to health
      disparities. Our research suggests that in Hispanic children, behavioral
      interventions toward improving sleep duration accomplished by earlier bedtimes or
      delayed school start times and mechanistic studies to unravel any inherent
      tendency toward a delayed sleep phase are needed.

PMID- 26299469
TI  - Elliot D. Weitzman MD and early sleep research and sleep medicine in New York.

PMID- 26299470
TI  - Sleep-stage transitions during polysomnographic recordings as diagnostic features
      of type 1 narcolepsy.
AB  - OBJECTIVE: Type 1 narcolepsy/hypocretin deficiency is characterized by excessive
      daytime sleepiness, sleep fragmentation, and cataplexy. Short rapid eye movement
      (REM) latency (<=15 min) during nocturnal polysomnography (PSG) or during naps of
      the multiple sleep latency test (MSLT) defines a sleep-onset REM sleep period
      (SOREMP), a diagnostic hallmark. We hypothesized that abnormal sleep transitions
      other than SOREMPs can be identified in type 1 narcolepsy. METHODS: Sleep-stage
      transitions (one to 10 epochs to one to five epochs of any other stage) and bout
      length features (one to 10 epochs) were extracted from PSGs. The first 15 min of
      sleep were excluded when a nocturnal SOREMP was recorded. F(0.1) measures and
      receiver operating characteristic curves were used to identify specific (>=98%)
      features. A data set of 136 patients and 510 sex- and age-matched controls was
      used for the training. A data set of 19 cases and 708 sleep-clinic patients was
      used for the validation. RESULTS: (1) >=5 transitions from >=5 epochs of stage N1
      or W to >=2 epochs of REM sleep, (2) >=22 transitions from >=3 epochs of stage N2
      or N3 to >=2 epochs of N1 or W, and (3) >=16 bouts of >=6 epochs of N1 or W were
      found to be highly specific (>=98%). Sensitivity ranged from 16% to 30%, and it
      did not vary substantially with and without medication or a nocturnal SOREMP. In
      patients taking antidepressants, nocturnal SOREMPs occurred much less frequently
      (16% vs. 36%, p < 0.001). CONCLUSIONS: Increased sleep-stage transitions notably
      from >=2.5 min of W/N1 into REM are specifically diagnostic for narcolepsy
      independent of a nocturnal SOREMP.

PMID- 26299471
TI  - Impact of television on the quality of sleep in preschool children.
AB  - OBJECTIVES: We aimed to investigate the impact of different habits concerning
      television (TV) use and the time of day in which TV is watched on the sleep
      quality of young children. METHODS: Parents of 100 healthy children (58% boys,
      mean age of 2.7 +/- 1.5 years) attending a routine health check completed the
      Sleep Disturbance Scale for Children (SDSC) and a questionnaire concerning TV and
      electronic media use. Children were divided into those with a normal (SDSC-) or
      abnormal (SDSC+) questionnaire score. TV viewing habits were compared between
      groups. RESULTS: The total sleep time and total TV viewing time were not
      different between groups. A TV set was inside each child's bedroom in 51% of
      participants. Children with a TV in their bedroom showed significantly higher
      scores in the "sleep terrors," "nightmares," "sleep talking," and "tired when
      waking up" responses of the SDSC (P = 0.02, 0.01, 0.01, and 0.01, respectively).
      Children with a TV in their room had an odds ratio (95% confidence interval) of
      3.29 (1.08-9.99) for having an abnormal SDSC. Evening TV viewers had
      significantly higher SDSC scores compared with those who watched TV earlier
      during the day (P = 0.04). CONCLUSIONS: The presence of a TV set in the child's
      bedroom was associated with significant reductions in the quality of young
      children's sleep. Evening exposure to TV was associated with significantly worse
      sleep quality.

PMID- 26299472
TI  - The evidence for immunotherapy in dermatomyositis and polymyositis: a systematic
      review.
AB  - Dermatomyositis and polymyositis are rare chronic inflammatory disorders with
      significant associated morbidity and mortality despite treatment. High-dose
      corticosteroids in addition to other interventions such as immunosuppressants,
      immunomodulators, and more recently, biologics are commonly used in clinical
      practice; however, there are no clear guidelines directing their use. Our
      objective was to systematically review the evidence for immunotherapy in the
      treatment of dermatomyositis and polymyositis. Relevant studies were identified
      through Embase and PubMed database searches. Trials were selected using pre
      determined selection criteria and then assessed for quality. Randomized
      controlled trials and experimental studies without true randomization and
      including adult patients with definite or probable dermatomyositis or
      polymyositis were evaluated. Any type of immunotherapy was considered. Clinical
      improvement, judged by assessment of muscle strength after 6 months, was the
      primary outcome. Secondary outcomes included IMACS definition of improvement,
      improvements in patient and physician global scores, physical function, and
      muscle enzymes. Twelve studies met eligibility criteria. Differences in trial
      design, quality, and variable reporting of baseline characteristics and outcomes
      made direct comparison impossible. Although no treatment can be recommended on
      the basis of this review, improved outcomes were demonstrated with a number of
      agents including methotrexate, azathioprine, ciclosporin, rituximab, and
      intravenous immunoglobulin. Plasmapheresis and leukapheresis were of no apparent
      benefit. More high-quality randomized controlled trials are needed to establish
      the role of immunosuppressive agents in the treatment of these conditions and the
      clinical context in which they are most likely to be beneficial.

PMID- 26299473
TI  - Clonally Related Forebrain Interneurons Disperse Broadly across Both Functional
      Areas and Structural Boundaries.
AB  - The medial ganglionic eminence (MGE) gives rise to the majority of mouse
      forebrain interneurons. Here, we examine the lineage relationship among MGE
      derived interneurons using a replication-defective retroviral library containing
      a highly diverse set of DNA barcodes. Recovering the barcodes from the mature
      progeny of infected progenitor cells enabled us to unambiguously determine their
      respective lineal relationship. We found that clonal dispersion occurs across
      large areas of the brain and is not restricted by anatomical divisions. As such,
      sibling interneurons can populate the cortex, hippocampus striatum, and globus
      pallidus. The majority of interneurons appeared to be generated from asymmetric
      divisions of MGE progenitor cells, followed by symmetric divisions within the
      subventricular zone. Altogether, our findings uncover that lineage relationships
      do not appear to determine interneuron allocation to particular regions. As such,
      it is likely that clonally related interneurons have considerable flexibility as
      to the particular forebrain circuits to which they can contribute. 

PMID- 26299475
TI  - Response to letter to the Editor: "Similarity between studies of dihydromyricetin
      and resveratrol for NAFLD".

PMID- 26299474
TI  - Wide Dispersion and Diversity of Clonally Related Inhibitory Interneurons.
AB  - The mammalian neocortex is composed of two major neuronal cell types with
      distinct origins: excitatory pyramidal neurons and inhibitory interneurons,
      generated in dorsal and ventral progenitor zones of the embryonic telencephalon,
      respectively. Thus, inhibitory neurons migrate relatively long distances to reach
      their destination in the developing forebrain. The role of lineage in the
      organization and circuitry of interneurons is still not well understood.
      Utilizing a combination of genetics, retroviral fate mapping, and lineage
      specific retroviral barcode labeling, we find that clonally related interneurons
      can be widely dispersed while unrelated interneurons can be closely clustered.
      These data suggest that migratory mechanisms related to the clustering of
      interneurons occur largely independent of their clonal origin.

PMID- 26299476
TI  - Popularity differentially predicts reactive and proactive aggression in early
      adolescence.
AB  - Previous research has indicated that peer popularity is associated with
      aggressive behavior. However, it is not yet clear whether popularity is uniquely
      related to different functions of aggression. In this study, we examined
      associations between peer-perceived popularity, and reactive and proactive
      aggression using a cross-sectional and a longitudinal design. Yearly sociometric
      measures of popularity, and reactive and proactive aggression were gathered from
      266 seventh and eight grade adolescents (Mage grade 7 = 12.80, SDage  = .40).
      Popularity was positively correlated with proactive aggression and negatively
      correlated with reactive aggression, both concurrently as over time. Curvilinear
      trends indicated that a significant minority of low versus high popular
      adolescents showed both functions of aggression. Somewhat stronger effects of
      popularity on proactive aggression were found for boys than girls. Stably popular
      adolescents showed the highest levels of proactive aggression, whereas stably
      unpopular youth showed the highest levels of reactive aggression. Implications
      and directions for future research are discussed.

PMID- 26299478
TI  - Finite-Element Extrapolation of Myocardial Structure Alterations Across the
      Cardiac Cycle in Rats.
AB  - Myocardial microstructures are responsible for key aspects of cardiac mechanical
      function. Natural myocardial deformation across the cardiac cycle induces
      measurable structural alteration, which varies across disease states. Diffusion
      tensor magnetic resonance imaging (DT-MRI) has become the tool of choice for
      myocardial structural analysis. Yet, obtaining the comprehensive structural
      information of the whole organ, in 3D and time, for subject-specific examination
      is fundamentally limited by scan time. Therefore, subject-specific finite-element
      (FE) analysis of a group of rat hearts was implemented for extrapolating a set of
      initial DT-MRI to the rest of the cardiac cycle. The effect of material symmetry
      (isotropy, transverse isotropy, and orthotropy), structural input, and warping
      approach was observed by comparing simulated predictions against in vivo MRI
      displacement measurements and DT-MRI of an isolated heart preparation at relaxed,
      inflated, and contracture states. Overall, the results indicate that, while
      ventricular volume and circumferential strain are largely independent of the
      simulation strategy, structural alteration predictions are generally improved
      with the sophistication of the material model, which also enhances torsion and
      radial strain predictions. Moreover, whereas subject-specific transversely
      isotropic models produced the most accurate descriptions of fiber structural
      alterations, the orthotropic models best captured changes in sheet structure.
      These findings underscore the need for subject-specific input data, including
      structure, to extrapolate DT-MRI measurements across the cardiac cycle. 

PMID- 26299479
TI  - Statin Selection in Qatar Based on Multi-indication Pharmacotherapeutic Multi
      criteria Scoring Model, and Clinician Preference.
AB  - PURPOSE: Statin selection for the largest hospital formulary in Qatar is not
      systematic, not comparative, and does not consider the multi-indication nature of
      statins. There are no reports in the literature of multi-indication-based
      comparative scoring models of statins or of statin selection criteria weights
      that are based primarily on local clinicians' preferences and experiences. This
      study sought to comparatively evaluate statins for first-line therapy in Qatar,
      and to quantify the economic impact of this. METHODS: An evidence-based, multi
      indication, multi-criteria pharmacotherapeutic model was developed for the
      scoring of statins from the perspective of the main health care provider in
      Qatar. The literature and an expert panel informed the selection criteria of
      statins. Relative weighting of selection criteria was based on the input of the
      relevant local clinician population. Statins were comparatively scored based on
      literature evidence, with those exceeding a defined scoring threshold being
      recommended for use. FINDINGS: With 95% CI and 5% margin of error, the scoring
      model was successfully developed. Selection criteria comprised 28 subcriteria
      under the following main criteria: clinical efficacy, best publish evidence and
      experience, adverse effects, drug interaction, dosing time, and fixed dose
      combination availability. Outcome measures for multiple indications were related
      to effects on LDL cholesterol, HDL cholesterol, triglyceride, total cholesterol,
      and C-reactive protein. Atorvastatin, pravastatin, and rosuvastatin exceeded
      defined pharmacotherapeutic thresholds. Atorvastatin and pravastatin were
      recommended as first-line use and rosuvastatin as a nonformulary alternative. It
      was estimated that this would produce a 17.6% cost savings in statins
      expenditure. Sensitivity analyses confirmed the robustness of the evaluation's
      outcomes against input uncertainties. IMPLICATIONS: Incorporating a comparative
      evaluation of statins in Qatari practices based on a locally developed,
      transparent, multi-indication, multi-criteria scoring model has the potential to
      considerably reduce expenditures on statins. Atorvastatin and pravastatin should
      be the first-line statin therapies in the main Qatari health care provider, with
      rosuvastatin as an alternative.

PMID- 26299477
TI  - Histone variants and cellular plasticity.
AB  - The broad diversity of cell types within vertebrates arises from a unique genetic
      blueprint by combining intrinsic cellular information with developmental and
      other extrinsic signals. Lying at the interface between cellular signals and the
      DNA is the chromatin, a dynamic nucleoprotein complex that helps to mediate gene
      regulation. The most basic subunit of chromatin, the nucleosome, consists of DNA
      wrapped around histones, a set of proteins that play crucial roles as scaffolding
      molecules and regulators of gene expression. Growing evidence indicates that
      canonical histones are commonly replaced by protein variants before and during
      cellular transitions. We highlight exciting new results suggesting that histone
      variants are essential players in the control of cellular plasticity during
      development and in the adult nervous system. 

PMID- 26299480
TI  - Analysis of prescription pattern and guideline adherence in the management of
      asthma among medical institutions and physician specialties in Taiwan between
      2000 and 2010.
AB  - PURPOSE: The aim of this study was to evaluate prescription patterns of
      antiasthmatic medications in ambulatory care, guideline adherence by physician
      specialties and medical institutions, and the rate of hospitalization and
      emergency department visits due to asthma exacerbation. METHODS: The ambulatory
      visits between 2000 and 2010 from the Taiwan Longitudinal Health Insurance
      Database 2000 were analyzed for prescription trends. Seven classes of
      antiasthmatic medications were identified for prescription trend analysis.
      Prescription patterns of different medical institutions and physician specialties
      were further evaluated. FINDINGS: We studied 4495 patients with newly diagnosed
      asthma in 2000. Estimates indicated an increased use in fixed-dose combination of
      inhaled corticosteroids and long-acting beta2-agonists (3.6% in 2002 to 28.8% in
      2010) with decreased use of inhaled corticosteroids (14.5% in 2001 to 7.3% in
      2010). Xanthine was still the most frequently used medication for asthmatic
      patients (60.2% in 2001 and 45.2% in 2010). Another marked increase was the use
      of leukotriene receptor antagonists (2.6% in 2001 to 6.0% in 2010). In the
      studied population, the rate of hospital admission or emergency department visit
      moderately decreased from 1.42% to 0.59% during 10 years. Physicians in medical
      centers and regional hospitals, as well as asthma specialists, dominated the
      increased use of fixed-dose combinations of inhaled corticosteroids and long
      acting beta2-agonists and leukotriene receptor antagonists. IMPLICATIONS:
      Physicians in academic medical centers and asthma specialists achieved better
      adherence to the core recommendations of the international guidelines for asthma
      management. The reasons for guideline nonadherence among physicians in district
      hospitals and primary care clinics deserve health care professionals' attention
      and require further investigation.

PMID- 26299481
TI  - Immunohistochemical localization of GLUT3, MCT1, and MCT2 in the testes of mice
      and rats: the use of different energy sources in spermatogenesis.
AB  - Lactate represents a preferential energy substrate of germ cells rather than
      glucose. Testicular Sertoli cells are believed to produce lactate and pyruvate
      and to supply these to germ cells, particularly spermatocytes and spermatids.
      Monocarboxylate transporter (MCT), responsible for the transport of lactate and
      other monocarboxylates via the cell membrane, is abundant in the testes and sperm
      (MCT1, MCT2, and MCT4). For the uptake of glucose, germ cells within the
      seminiferous tubules and sperm have been known to intensely express GLUT3. The
      present study investigated expression profiles of MCTs and GLUTs and revealed
      their cellular and subcellular localization in the mouse and rat testis. An in
      situ hybridization analysis showed significant expressions of MCT1, MCT2, and
      GLUT3 mRNA in the testis. Immunohistochemically, spermatogonia, spermatocytes,
      and spermatids expressed MCT1 on their cell surfaces in a stage-dependent manner:
      in some seminiferous tubules, an intense expression of MCT1 was unique to the
      spermatogonia. MCT2 was restricted to the tails of elongated spermatids and
      sperm. An intense immunoreactivity for GLUT3 was shared by spermatocytes,
      spermatids, and sperm. Sertoli cells were devoid of any immunoreactivities for
      MCT1, MCT2, and GLUT3. The predominant energy source of germ cells may be lactate
      and other monocarboxylates--especially for spermatogonia, but glucose and other
      hexoses may be responsible for an energy supply to spermatocytes and spermatids.

PMID- 26299482
TI  - Foxc2 in pharyngeal arch mesenchyme is important for aortic arch artery
      remodelling and ventricular septum formation.
AB  - The forkhead box C2 (Foxc2) protein is a member of the forkhead/winged helix
      transcription factor family and plays an essential role in cardiovascular
      development. Previous studies showed that Foxc2 null mouse embryos die during
      midgestation or just after birth with severe cardiovascular defects, including
      interruption, coarctation of the aortic arch and ventricular septal defects.
      These are also seen in human congenital heart disease. However, the tissue
      specific role of Foxc2 in aortic arch remodelling is not yet fully understood.
      Here we show that Foxc2 is expressed in a restricted pattern in several cell
      populations, including the mesenchyme and endothelium of pharyngeal arch
      arteries, which are important for cardiovascular development. In this study, we
      use a conditional knockout approach to examine the tissue specific role of Foxc2
      in aortic arch remodelling. We demonstrate that mouse embryos lacking Foxc2 in
      Nkx2.5-expressing mesenchyme and endothelium of pharyngeal arch arteries display
      aortic arch interruption type B and ventricular septal defects. In contrast,
      conditional deletion of Foxc2 in Tie2-expressing endothelial cells does not
      result in aortic arch or ventricular septal defects, but does result in embryonic
      lethality due to peripheral oedema. Our data therefore provide for a detailed
      understanding of the role of mesenchymal Foxc2 in aortic arch remodelling and in
      the development of ventricular septum. 

PMID- 26299483
TI  - Structure of the methyl orange-binding site on human serum albumin and its color
      change mechanism.
AB  - The goal in this study was to clarify the color-change mechanisms of methyl
      orange (MO) bound to human serum albumin (HSA) and the structure of the binding
      site. The absorbance of the MOHSA complex was measured at 560 nm in solutions of
      varying pH (pH 2.4-6.6). The obtained pH-dependent experimental data were
      consistent with the data calculated using the Henderson-Hasselbalch equation and
      pKa values (3.8, MO; 1.4, carboxyl group). The extent of the binding of MO to an
      HSA molecule was determined to be 1-4 by performing surface plasmon resonance
      analysis. Furthermore, the binding of MO to HSA was inhibited by warfarin. A
      fitting model of MO to HSA was created to evaluate these results based on PDB
      data (warfarin-HSA complex: 2BXD) and protein-structure analysis. The color
      change mechanism of the MO-HSA complex appears to be as follows: the dissociated
      sulfo group of MO binds to Arg218/Lys444 sidechains through electrostatic
      interaction in the warfarin-binding site, and, subsequently, the color change
      occurs through a proton exchange between the diazenyl group and the gamma
      carboxyl group of Glu292. The color-changed MO is fixed in the warfarin-binding
      site. These results could support the development of a reliable dye-binding
      method and of a new method for staining diverse tissues that is based on a
      validated mechanism. 

PMID- 26299484
TI  - Protein expression profile related to cisplatin resistance in bladder cancer cell
      lines detected by two-dimensional gel electrophoresis.
AB  - We used a proteomic approach to compare the differentially regulated protein
      expression profiles of cisplatin-naive and cisplatin-resistant bladder cancer
      cell lines to screen candidate molecules related to cisplatin resistance. The
      cisplatin-resistant cell line T24 was established by the stepwise exposure of T24
      cells to up to 40 MUM of cisplatin. We performed a comprehensive study of protein
      expression in bladder cancer cell lines that included cisplatin-naive (T24) and
      cisplatin-resistant cells (T24CDDPR) by means of agarose two-dimensional gel
      electrophoresis followed by analysis of liquid chromatography tandem mass
      spectroscopy. We identified 25 obviously different spots for T24 and T24 CDDPR.
      Seven spots had increased expression and 18 spots had decreased expression in
      T24CDDPR compared to those in T24. Cytoskeletal proteins and enzyme modulators
      were prominent among differential proteins. Of the 25 proteins, we selected
      HNRNPA3, PCK2, PPL, PGK1, TKT, SERPINB2, GOT2, and EIF3A for further validation
      by Western blot. HNRNPA3, PGK1, TKT, and SERPINB2 had more than 1.5-times
      incremental expression in T24CDDPR compared to that in T24. PCK2 and PPL
      expressions were decreased less than 20% in T24CDDPR compared to that in T24. The
      results of 25 new proteins in this study could be valuable and could lead to the
      development of a new molecular marker. 

PMID- 26299485
TI  - GP2-expressing cells in the conjunctiva and tear ducts of mice: identification of
      a novel type of cells in the squamous stratified epithelium.
AB  - GP2 is a membrane-associated secretory protein originally identified in zymogen
      granules of pancreatic acinar cells. Recently, this glycoprotein has attracted
      attention as a marker substance of M cells of Peyer's patches and for its
      involvement in the selective uptake of pathological bacteria via M cells. When we
      stained the conjunctiva and tear ducts of mice using a GP2 antibody, all goblet
      cells in the squamous stratified epithelium of the conjunctiva were intensely
      immunolabeled, while goblet cells in the intestine and airway were devoid of the
      immunoreactivity, indicating that the conjunctiva contains a special type of
      goblet cell. Further immunostaining for GP-2 labeled dispersed cells of peculiar
      shapes within the stratified squamous epithelium in the lacrimal canaliculi,
      lacrimal sac, and nasolacrimal duct. The GP2-immunoreactive cells in the tear
      duct projected arched or branched processes toward the basement membrane.
      Electron-microscopically, immunogold particles for GP2 outlined the basolateral
      plasma membrane of both the conjuntival goblet cells and the peculiarly shaped
      cells in the tear duct. Intracellularly, GP2 products of the goblet cells were
      localized around secretory granules in the apical cytoplasm and those of the tear
      duct cells inside the vesicles. The luminal contents close to apical plasma
      membrane were heavily labeled with immunogold particles, suggesting an exocytosis
      based targeting of GP2 to the plasma membrane and its release into the lumen. The
      possible function of GP2 in tear ducts is discussed in relation to a defense
      system against invasive microoranisms and antigens. 

PMID- 26299486
TI  - ProGRP is a possible tumor marker for patients with Ewing sarcoma.
AB  - We analyzed serum ProGRP levels in patients with Ewing sarcoma, and found that 5
      out of 9 patients had elevated levels; the values range equally with those of
      patients with limited disease of small-cell lung carcinoma. Serum ProGRP levels
      in patients with bone and soft tissue malignancies other than Ewing sarcoma are
      not elevated. Immunohistochemical studies demonstrated that ProGRP-like
      immunoreactivities were detected in Ewing sarcoma tissues obtained from 2
      patients with elevated serum ProGRP levels, suggesting that ProGRP is a product
      of tumor cells of Ewing sarcoma. These results indicate that serum ProGRP could
      serve as a specific tumor marker for Ewing sarcoma. Since ProGRP is a major
      hormonal product of tumor cells of small-cell lung carcinoma, a typical
      neuroendocrine carcinoma, it is reasonable to postulate that the present study
      provides an evidence for Ewing sarcoma to possess neuroendocrine differentiation.

PMID- 26299487
TI  - What Are the Indications for Resection After an Episode of Sigmoid
      Diverticulitis?

PMID- 26299488
TI  - Hospital Readmissions: Are They Preventable?

PMID- 26299489
TI  - Recent Advances in Intestinal and Multivisceral Transplantation.

PMID- 26299490
TI  - Which Is Best for Abdominal Aortic Aneurysms Treatment with Chronic Renal
      Insufficiency: Endovascular Aneurysm Repair or Open Repair?

PMID- 26299491
TI  - What Is the Optimal Treatment of Papillary Thyroid Cancer?

PMID- 26299492
TI  - Does Diet Make a Difference Following Colon Surgery?

PMID- 26299494
TI  - Hospital Accreditation and Bariatric Surgery: Is It Important?

PMID- 26299493
TI  - Principles in Management of Soft Tissue Sarcoma.

PMID- 26299495
TI  - Trainee Participation in Emergency Surgery: What Are the Consequences?

PMID- 26299496
TI  - Laparoscopic Pancreaticoduodenectomy: Is It an Effective Procedure for Pancreatic
      Ductal Adenocarcinoma?

PMID- 26299497
TI  - Bariatric Surgery versus Intensive Medical Weight Management for Type 2 Diabetes.

PMID- 26299498
TI  - Should Steroids Be Used During Endovascular Aortic Repair?

PMID- 26299499
TI  - Are Higher Hospital Venous Thromboembolism Rates an Indicator of Better Quality?:
      Evaluation of the Validity of a Hospital Quality Measure.

PMID- 26299500
TI  - Fluid Restriction During Pancreaticoduodenectomy: Is It Effective in Reducing
      Postoperative Complications?

PMID- 26299501
TI  - Is There a Relationship Between Patient Satisfaction and Favorable Surgical
      Outcomes?

PMID- 26299502
TI  - Does Volume Affect Outcome with Severe Trauma?

PMID- 26299503
TI  - Hyperparathyroidism: What Preoperative Imaging Is Necessary?

PMID- 26299504
TI  - Abscess After Appendectomy: Predisposing Factors.

PMID- 26299505
TI  - A sensitive turn-on fluorescent probe for intracellular imaging of glutathione
      using single-layer MnO2 nanosheet-quenched fluorescent carbon quantum dots.
AB  - A sensitive turn-on fluorescent sensor based on single-layer MnO2 nanosheet
      quenched fluorescent carbon quantum dots has been developed for rapid and
      selective sensing of glutathione in aqueous solutions, as well as in living
      cells. 

PMID- 26299507
TI  - Visual features for perception, attention, and working memory: Toward a three
      factor framework.
AB  - Visual features are the general building blocks for attention, perception, and
      working memory. Here, I explore the factors which can quantitatively predict all
      the differences they make in various paradigms. I tried to combine the strengths
      of experimental and correlational approaches in a novel way by developing an
      individual-item differences analysis to extract the factors from 16 stimulus
      types on the basis of their roles in eight tasks. A large sample size (410)
      ensured that all eight tasks had a reliability (Cronbach's alpha) of no less than
      0.975, allowing the factors to be precisely determined. Three orthogonal factors
      were identified which correspond respectively to featural strength (i.e., how
      close a stimulus is to a basic feature), visual strength (i.e., visual quality of
      the stimulus), and spatial strength (i.e., how well a stimulus can be represented
      as a spatial structure). Featural strength helped substantially in all the tasks
      but moderately less so in perceptual discrimination; visual strength helped
      substantially in low-level tasks but not in high-level tasks; and spatial
      strength helped change detection but hindered ensemble matching and visual
      search. Jointly, these three factors explained 96.4% of all the variances of the
      eight tasks, making it clear that they account for almost everything about the
      roles of these 16 stimulus types in these eight tasks. 

PMID- 26299506
TI  - Spatiotemporal drug delivery using laser-generated-focused ultrasound system.
AB  - Laser-generated-focused ultrasound (LGFU) holds promise for the high-precision
      ultrasound therapy owing to its tight focal spot, broad frequency band, and
      stable excitation with minimal ultrasound-induced heating. We here report the
      development of the LGFU as a stimulus for promoted drug release from microgels
      integrated with drug-loaded polymeric nanoparticles. The pulsed waves of
      ultrasound, generated by a carbon black/polydimethylsiloxane (PDMS)-photoacoustic
      lens, were introduced to trigger the drug release from alginate microgels
      encapsulated with drug-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles.
      We demonstrated the antibacterial capability of this drug delivery system against
      Escherichia coli by the disk diffusion method, and antitumor efficacy toward the
      HeLa cell-derived tumor spheroids in vitro. This novel LGFU-responsive drug
      delivery system provides a simple and remote approach to precisely control the
      release of therapeutics in a spatiotemporal manner and potentially suppress
      detrimental effects to the surrounding tissue, such as thermal ablation. 

PMID- 26299508
TI  - Sinonasal renal cell-like adenocarcinomas: robust carbonic anhydrase expression.
AB  - We report 3 new patients with sinonasal renal cell-like adenocarcinoma (SNRCLA).
      One case submitted in consultation demonstrated robust carbonic anhydrase IX (CA
      IX) expression, leading us to a broader inquiry of CA-IX and carbonic anhydrase
      II (CA-II) expression in other SNRCLA, Schneiderian tissues, and histologic
      mimickers. Robust cytoplasmic and membranous CA-IX expression is demonstrated in
      6 of 7 SNRCLAs; CA-II expression was demonstrated in 2 of 5 cases. Robust,
      diffuse CA-II expression is demonstrated throughout sinonasal seromucinous glands
      in all 10 normal Schneiderian samples. CA-IX is also expressed in all normal
      sinonasal samples, albeit focally. The closest salivary mimic to SNRCLA is
      hyalinizing salivary clear cell carcinoma; only focal CA-IX expression was
      demonstrated in 1 of 2 cases studied. Carbonic anhydrase expression in
      Schneiderian tissue speaks to its role in regulating the ion concentration of
      sinonasal secretions and may also explain the origin of this rare tumor. 

PMID- 26299509
TI  - Rare variants in the spectrum of human herpesvirus 8/Epstein-Barr virus
      copositive lymphoproliferations.
AB  - We report 2 rare variants in the spectrum of human herpesvirus 8 (HHV8)/Epstein
      Barr virus (EBV)-copositive lymphoproliferations arising in HIV-seronegative
      patients, including a large B-cell lymphoma arising in the setting of
      multicentric Castleman disease and a germinotropic lymphoproliferative disorder.
      In the first case, histology revealed features of multicentric Castleman disease
      and a proliferation of large lymphoid cells forming clusters or arcs or rings
      replacing the periphery of follicles or sheets of frank lymphoma outside the
      follicles. In the second case, a proliferation of large lymphoid cells totally or
      partially invaded follicle germinal centers. In both cases, the large cells were
      positive for EBV-encoded small RNA, HHV8 (LANA-1), MUM1/IRF4, and CD38 and
      negative for CD45, CD79a, CD10, BCL6, and CD138. In the large B-cell lymphoma,
      the large cells did not express detectable cytoplasmic immunoglobulin light- and
      heavy-chains, whereas in the germinotropic lymphoproliferative disorder, the
      large cells expressed MU heavy chain. The present cases broaden the spectrum of
      HHV-EBV--copositive lymphoproliferations. 

PMID- 26299510
TI  - Mechanical Properties of Water-Assembled Graphene Oxide Langmuir Monolayers:
      Guiding Controlled Transfer.
AB  - Liquid-phase transfer of graphene oxide (GO) and reduced graphene oxide (RGO)
      monolayers is investigated from the perspective of the mechanical properties of
      these films. Monolayers are assembled in a Langmuir-Blodgett trough, and
      oscillatory barrier measurements are used to characterize the resulting
      compressive and shear moduli as a function of surface pressure. GO monolayers are
      shown to develop a significant shear modulus (10-25 mN/m) at relevant surface
      pressures while RGO monolayers do not. The existence of a shear modulus indicates
      that GO is acting as a two-dimensional solid driven by strong interaction between
      the individual GO sheets. The absence of such behavior in RGO is attributed to
      the decrease in oxygen moieties on the sheet basal plane, permitting RGO sheets
      to slide across one another with minimum energy dissipation. Knowledge of this
      two-dimensional solid behavior is exploited to successfully transfer large-area,
      continuous GO films to hydrophobic Au substrates. The key to successful transfer
      is the use of shallow-angle dipping designed to minimize tensile stress present
      during the insertion or extraction of the substrate. A shallow dip angle on
      hydrophobic Au does not impart a beneficial effect for RGO monolayers, as these
      monolayers do not behave as two-dimensional solids and do not remain coherent
      during the transfer process. We hypothesize that this observed correlation
      between monolayer mechanical properties and continuous film transfer success is
      more universally applicable across substrate hydrophobicities and could be
      exploited to control the transfer of films composed of two-dimensional materials.

PMID- 26299511
TI  - The role of lymph node revealing solution on the improvement of lymph node
      harvest in colorectal cancer specimens.
AB  - AIM: The correct analysis of lymph node status is one of the most important
      parameters for the accurate pathological diagnosis of colorectal cancer. Our aim
      was to evaluate the number of lymph nodes among the specimens obtained from
      colorectal resections due to colorectal cancer, before and after the routine use
      of a lymph node revealing solution (LNRS). METHOD: Data from 780 surgical
      specimens from patients of both genders with colorectal cancer were studied. The
      cases were divided chronologically into two groups: the conventional group
      included 497 specimens treated with conventional methods, i.e. without the use of
      the LNRS (January 2000 to July 2007), and the LNRS group included 283 specimens
      examined through the routine use of this solution (August 2007 to July 2012).
      RESULTS: Most patients were female (57.4%) with a median age of 62 years. The
      median lymph node number was 18, and 75.9% of the cases (592) had 12 or more
      nodes dissected. Lymph node metastases were noted in 334 cases (42.8%). A median
      of 24 lymph nodes was dissected in the LNRS group compared to 15 in the
      conventional group (P < 0.001). The LNRS group had 9.2% of cases with fewer than
      12 lymph nodes dissected compared with 32.6% in the conventional group (P <
      0.001). CONCLUSIONS: The use of the LNRS increases the number of lymph nodes
      obtained from colorectal cancer surgical specimens and can help to reduce the
      number of cases with < 12 lymph nodes.

PMID- 26299512
TI  - Long-Lasting Crossmodal Cortical Reorganization Triggered by Brief Postnatal
      Visual Deprivation.
AB  - Animal and human studies have demonstrated that transient visual deprivation
      early in life, even for a very short period, permanently alters the response
      properties of neurons in the visual cortex and leads to corresponding behavioral
      visual deficits. While it is acknowledged that early-onset and longstanding
      blindness leads the occipital cortex to respond to non-visual stimulation, it
      remains unknown whether a short and transient period of postnatal visual
      deprivation is sufficient to trigger crossmodal reorganization that persists
      after years of visual experience. In the present study, we characterized brain
      responses to auditory stimuli in 11 adults who had been deprived of all patterned
      vision at birth by congenital cataracts in both eyes until they were treated at 9
      to 238 days of age. When compared to controls with typical visual experience, the
      cataract-reversal group showed enhanced auditory-driven activity in focal visual
      regions. A combination of dynamic causal modeling with Bayesian model selection
      indicated that this auditory-driven activity in the occipital cortex was better
      explained by direct cortico-cortical connections with the primary auditory cortex
      than by subcortical connections. Thus, a short and transient period of visual
      deprivation early in life leads to enduring large-scale crossmodal reorganization
      of the brain circuitry typically dedicated to vision.

PMID- 26299513
TI  - Loss of Centrobin Enables Daughter Centrioles to Form Sensory Cilia in
      Drosophila.
AB  - Sensory cilia are organelles that convey information to the cell from the
      extracellular environment. In vertebrates, ciliary dysfunction results in
      ciliopathies that in humans comprise a wide spectrum of developmental disorders.
      In Drosophila, sensory cilia are found only in the neurons of type I sensory
      organs, but ciliary dysfunction also has dramatic consequences in this organism
      because it impairs the mechanosensory properties of bristles and chaetae and
      leads to uncoordination, a crippling condition that causes lethality shortly
      after eclosion. The cilium is defined by the ciliary membrane, a protrusion of
      the cell membrane that envelops the core structure known as the axoneme, a
      microtubule array that extends along the cilium from the basal body. In
      vertebrates, basal body function requires centriolar distal and subdistal
      appendages and satellites. Because these structures are acquired through
      centriole maturation, only mother centrioles can serve as basal bodies. Here, we
      show that although centriole maturity traits are lacking in Drosophila, basal
      body fate is reserved to mother centrioles in Drosophila type I neurons.
      Moreover, we show that depletion of the daughter-centriole-specific protein
      Centrobin (CNB) enables daughter centrioles to dock on the cell membrane and to
      template an ectopic axoneme that, although structurally defective, protrudes out
      of the cell and is enveloped by a ciliary membrane. Conversely, basal body
      capability is inhibited in mother centrioles modified to carry CNB. These results
      reveal the crucial role of CNB in regulating basal body function in Drosophila
      ciliated sensory organs.

PMID- 26299514
TI  - A Higher Brain Circuit for Immediate Integration of Conflicting Sensory
      Information in Drosophila.
AB  - Animals continuously evaluate sensory information to decide on their next action.
      Different sensory cues, however, often demand opposing behavioral responses. How
      does the brain process conflicting sensory information during decision making?
      Here, we show that flies use neural substrates attributed to odor learning and
      memory, including the mushroom body (MB), for immediate sensory integration and
      modulation of innate behavior. Drosophila melanogaster must integrate
      contradictory sensory information during feeding on fermenting fruit that
      releases both food odor and the innately aversive odor CO2. Here, using this
      framework, we examine the neural basis for this integration. We have identified a
      local circuit consisting of specific glutamatergic output and PAM dopaminergic
      input neurons with overlapping innervation in the MB-beta'2 lobe region, which
      integrates food odor and suppresses innate avoidance. Activation of food odor
      responsive dopaminergic neurons reduces innate avoidance mediated by CO2
      responsive MB output neurons. We hypothesize that the MB, in addition to its long
      recognized role in learning and memory, serves as the insect's brain center for
      immediate sensory integration during instantaneous decision making. 

PMID- 26299515
TI  - Human Hippocampal Dynamics during Response Conflict.
AB  - Besides its relevance for declarative memory functions, hippocampal activation
      has been observed during disambiguation of uncertainty and conflict. Uncertainty
      and conflict may arise on various levels. On the perceptual level, the
      hippocampus has been associated with signaling of contextual deviance and
      disambiguation of similar items (i.e., pattern separation). Furthermore,
      conflicts can occur on the response level. Animal experiments showed a role of
      the hippocampus for inhibition of prevailing response tendencies and suppression
      of automatic stimulus-response mappings, potentially related to increased theta
      oscillations (3-8 Hz). In humans, a recent fMRI study demonstrated hippocampal
      involvement in approach-avoidance conflicts. However, the more general
      significance of hippocampal activity for dealing with response conflicts also on
      a cognitive level is still unknown. Here, we investigated the role of the
      hippocampus for response conflict in the Stroop task by combining intracranial
      electroencephalography (iEEG) recordings from the hippocampus of epilepsy
      patients with region of interest-based fMRI in healthy participants. Both methods
      revealed converging evidence that the hippocampus is recruited in a regionally
      specific manner during response conflict. Moreover, our iEEG data show that this
      activation depends on theta oscillations and is relevant for successful response
      conflict resolution.

PMID- 26299516
TI  - Functional Divergence of Two Secreted Immune Proteases of Tomato.
AB  - Rcr3 and Pip1 are paralogous secreted papain-like proteases of tomato. Both
      proteases are inhibited by Avr2 from the fungal pathogen Cladosporium fulvum, but
      only Rcr3 acts as a co-receptor for Avr2 recognition by the tomato Cf-2 immune
      receptor. Here, we show that Pip1-depleted tomato plants are hyper-susceptible to
      fungal, bacterial, and oomycete plant pathogens, demonstrating that Pip1 is an
      important broad-range immune protease. By contrast, in the absence of Cf-2, Rcr3
      depletion does not affect fungal and bacterial infection levels but causes
      increased susceptibility only to the oomycete pathogen Phytophthora infestans.
      Rcr3 and Pip1 reside on a genetic locus that evolved over 36 million years ago.
      These proteins differ in surface-exposed residues outside the substrate-binding
      groove, and Pip1 is 5- to 10-fold more abundant than Rcr3. We propose a model in
      which Rcr3 and Pip1 diverged functionally upon gene duplication, possibly driven
      by an arms race with pathogen-derived inhibitors or by coevolution with the Cf-2
      immune receptor detecting inhibitors of Rcr3, but not of Pip1.

PMID- 26299517
TI  - The Deubiquitinase USP37 Regulates Chromosome Cohesion and Mitotic Progression.
AB  - A bipolar mitotic spindle facilitates the equal segregation of chromosomes to two
      daughter cells. To achieve bipolar attachment of microtubules to kinetochores of
      sister chromatids, chromatids must remain paired after replication. This cohesion
      is mediated by the conserved cohesin complex comprised of SMC1, SMC3, SCC1, and
      either SA1 or SA2 in humans. Because defects in spindle assembly or sister
      chromatid cohesion can lead to aneuploidy in daughter cells, proper regulation of
      these processes is essential for fidelity in chromosome segregation. In an RNAi
      screen for regulators of spindle assembly, we identify the deubiquitinase USP37
      as a regulator of mitotic progression, centrosome integrity, and chromosome
      alignment. USP37 associates with cohesin and contributes to sister chromatid
      resolution. Cohesion defects are rescued by expression of an RNAi-resistant
      USP37, but not the catalytically impaired USP37(C350A) mutant. Further, USP37
      associates with WAPL, a negative regulator of cohesion necessary for cohesin
      release in prophase, in a manner dependent on USP37's second and third ubiquitin
      interacting motifs. Depletion of USP37 reduces the stability of chromatin
      associated WAPL and increases the fraction of WAPL that is more heavily
      ubiquitylated in mitosis. Consistently, overexpression of USP37(C350A) results in
      increased modification of WAPL, and addition of purified USP37(WT), but not
      USP37(C350A), to WAPL immunoprecipitates results in a reduction of ubiquitylated
      products. Taken together, our results ascribe a novel function for USP37 in
      mitotic progression and further suggest that USP37 positively regulates the
      stability of chromatin-associated WAPL to facilitate sister chromatid resolution.

PMID- 26299518
TI  - The Formin FMNL3 Controls Early Apical Specification in Endothelial Cells by
      Regulating the Polarized Trafficking of Podocalyxin.
AB  - Angiogenesis is the fundamental process by which new blood vessels form from pre
      existing vasculature. It plays a critical role in the formation of the
      vasculature during development and is triggered in response to tissue hypoxia in
      adult organisms. This process requires complex and coordinated regulation of the
      endothelial cell cytoskeleton to control cell shape and polarity. In our previous
      work, we showed that the cytoskeletal regulator FMNL3/FRL2 controls the alignment
      of stabilized microtubules during polarized endothelial cell elongation and that
      depletion of FMNL3 retards elongation of the intersegmental vessels in zebrafish.
      Recent work has shown that FMNL3 is also needed for vascular lumen formation, a
      critical element of the formation of functional vessels. Here, we show that FMNL3
      interacts with Cdc42 and RhoJ, two Rho family GTPases known to be required for
      lumen formation. FMNL3 and RhoJ are concentrated at the early apical surface, or
      AMIS, and regulate the formation of radiating actin cables from this site. In
      diverse biological systems, formins mediate polarized trafficking through the
      generation of similar actin filaments tracks. We show that FMNL3 and RhoJ are
      required for polarized trafficking of podocalyxin to the early apical surface--an
      important event in vascular lumenogenesis.

PMID- 26299519
TI  - The Limits of Shape Recognition following Late Emergence from Blindness.
AB  - Visual object recognition develops during the first years of life. But what if
      one is deprived of vision during early post-natal development? Shape information
      is extracted using both low-level cues (e.g., intensity- or color-based contours)
      and more complex algorithms that are largely based on inference assumptions
      (e.g., illumination is from above, objects are often partially occluded).
      Previous studies, testing visual acuity using a 2D shape-identification task (Lea
      symbols), indicate that contour-based shape recognition can improve with visual
      experience, even after years of visual deprivation from birth. We hypothesized
      that this may generalize to other low-level cues (shape, size, and color), but
      not to mid-level functions (e.g., 3D shape from shading) that might require prior
      visual knowledge. To that end, we studied a unique group of subjects in Ethiopia
      that suffered from an early manifestation of dense bilateral cataracts and were
      surgically treated only years later. Our results suggest that the newly sighted
      rapidly acquire the ability to recognize an odd element within an array, on the
      basis of color, size, or shape differences. However, they are generally unable to
      find the odd shape on the basis of illusory contours, shading, or occlusion
      relationships. Little recovery of these mid-level functions is seen within 1 year
      post-operation. We find that visual performance using low-level cues is
      relatively robust to prolonged deprivation from birth. However, the use of
      pictorial depth cues to infer 3D structure from the 2D retinal image is highly
      susceptible to early and prolonged visual deprivation.

PMID- 26299520
TI  - Impact of cardiovascular risk factors and related comorbid conditions and medical
      therapy reported at baseline on the treatment response to tadalafil 5 mg once
      daily in men with lower urinary tract symptoms associated with benign prostatic
      hyperplasia: an integrated analysis of four randomised, double-blind, placebo
      controlled, clinical trials.
AB  - PURPOSE: The influence of cardiovascular risk factors/comorbidities on response
      to oral once-daily tadalafil 5 mg was explored in men with lower urinary tract
      symptoms associated with benign prostatic hyperplasia (LUTS/BPH). METHODS: This
      post hoc analysis pooled data from four double-blind studies in which 1498 men
      with > 6-mo history of LUTS/BPH were randomised and received either once-daily
      placebo (n = 746) or tadalafil 5 mg (n = 752) for 12 weeks. Descriptive
      statistics were reported for changes in total International Prostate Symptom
      Score (IPSS), IPSS voiding and storage subscores, and IPSS quality-of-life (QoL)
      index. Treatment group differences by baseline clinical and cardiovascular
      factors and medical therapies were examined using analysis of covariance.
      RESULTS: Tadalafil was effective in men with LUTS/BPH and cardiovascular risk
      factors/comorbidities except for patients receiving > 1 antihypertensive
      medication. Placebo-adjusted least squares (LS) mean improvements in total IPSS
      were -1.2 (95% CI: -2.5 to -0.0) in men taking > 1 antihypertensive medication
      vs. -3.3 (95% CI: -4.4 to -2.1) in men taking one medication (interaction p =
      0.020). In addition, placebo-adjusted LS mean improvements in total IPSS were 
      0.2 (95% CI, -2.1 to 1.7) in men who reported use of diuretics vs. -2.8 (95% CI, 
      3.7 to -1.9) in men who reported taking other antihypertensive medications vs. 
      2.3 (95% CI, -3.2 to -1.5) in men who reported not using any antihypertensive
      drug (p-value for interaction = 0.053). CONCLUSIONS: Once-daily tadalafil 5 mg
      improved LUTS/BPH, regardless of severity, in men with coexisting cardiovascular
      risk factors/comorbidities, except for patients with history of > 1 drug for
      arterial hypertension. Use of diuretics may contribute to patients' perception of
      a negated efficacy of tadalafil on LUTS/BPH. Comorbidities should be considered
      when choosing the optimal medicine to treat men with LUTS/BPH.

PMID- 26299521
TI  - Lack of support for Rensch's rule in an intraspecific test using red flour beetle
      (Tribolium castaneum) populations.
AB  - Rensch's rule proposes a universal allometric scaling phenomenon across species
      where sexual size dimorphism (SSD) has evolved: in taxa with male-biased
      dimorphism, degree of SSD should increase with overall body size, and in taxa
      with female-biased dimorphism, degree of SSD should decrease with increasing
      average body size. Rensch's rule appears to hold widely across taxa where SSD is
      male-biased, but not consistently when SSD is female-biased. Furthermore, studies
      addressing this question within species are rare, so it remains unclear whether
      this rule applies at the intraspecific level. We assess body size and SSD within
      Tribolium castaneum (Herbst), a species where females are larger than males,
      using 21 populations derived from separate locations across the world, and
      maintained in isolated laboratory culture for at least 20 years. Body size, and
      hence SSD patterns, are highly susceptible to variations in temperature, diet
      quality and other environmental factors. Crucially, here we nullify interference
      of such confounds as all populations were maintained under identical conditions
      (similar densities, standard diet and exposed to identical temperature, relative
      humidity and photoperiod). We measured thirty beetles of each sex for all
      populations, and found body size variation across populations, and (as expected)
      female-biased SSD in all populations. We test whether Rensch's rule holds for our
      populations, but find isometry, i.e. no allometry for SSD. Our results thus show
      that Rensch's rule does not hold across populations within this species. Our
      intraspecific test matches previous interspecific studies showing that Rensch's
      rule fails in species with female-biased SSD.

PMID- 26299522
TI  - Chemical analysis of essential oils from different parts of Ferula communis L.
      growing in central Italy.
AB  - Ferula communis is a showy herbaceous plant typical of the Mediterranean area
      where it is used as a traditional medicine. The plant is a source of bioactive
      compounds such as daucane sesquiterpenes and prenylated coumarins. In Italy, most
      of phytochemical studies focused on Sardinian populations where poisonous and
      nonpoisonous chemotypes were found, while investigations on peninsular
      populations are scarce. In this work, we report the chemical characterisation of
      the essential oils obtained from different parts of F. communis growing in
      central Italy. The chemical profiles of the plant parts, as detected by GC-FID
      and GC-MS, were different from each other and from those reported in insular
      populations. Notably, alpha-pinene (10.5%), gamma-terpinene (7.6%) and hedycariol
      (8.4%) were the major volatile constituents in flowers; alpha-pinene (55.9%),
      beta-pinene (16.8%) and myrcene (5.9%) in fruits; beta-eudesmol (12.1%), alpha
      eudesmol (12.1%) and hedycariol (10.3%) in leaves; (E)-beta-farnesene (9.5%),
      beta-cubebene (8.2%) and (E)-caryophyllene (7.2%) in roots. The volatile profiles
      detected did not allow to classify the investigated central Italy population into
      the poisonous and nonpoisonous chemotypes previously described in Sardinia. 

PMID- 26299523
TI  - The surface roughness, but not the water molecular orientation varies with
      temperature at the water-air interface.
AB  - We examine the temperature dependence of the interfacial molecular structure at
      the water-air interface by combining experimental and simulated sum-frequency
      generation (SFG) spectroscopy. The experimental SFG spectra of the OH-stretching
      mode show a decrease in the amplitude at ~3300 cm(-1) with increasing
      temperature, while the 3700 cm(-1) 'free OH' SFG feature is insensitive to
      temperature changes. The simulated spectra are in excellent agreement with
      experiment. A comparison between interfacial SFG spectra and bulk infrared/Raman
      spectra reveals that the variation of the SFG signal due to the temperature
      change is not caused by a temperature-dependent OH bond orientation of the
      interfacial water molecules, but can be fully accounted for by the temperature
      dependence of the optical response of water. These results indicate that while
      the thickness of the interfacial region varies with temperature, the molecular
      organization of interfacial water at the water-air interface is surprisingly
      insensitive to temperature changes. 

PMID- 26299524
TI  - LC/MS-based polar metabolite profiling reveals gender differences in serum from
      patients with myocardial infarction.
AB  - Myocardial infarction (MI), a leading cause of death worldwide, results from
      prolonged myocardial ischemia with necrosis of myocytes due to a blood supply
      obstruction to an area of the heart. Many studies have reported gender-related
      differences in the clinical features of MI, but the reasons for these differences
      remain unclear. In this study, we applied ultra-performance liquid
      chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) and
      various statistical methods-such as multivariate, pathway, and correlation
      analyses-to identify gender-specific metabolic patterns in polar metabolites in
      serum from healthy individuals and patients with MI. Patients with diagnosed MI
      (n=68), and age- and body mass index-matched healthy individuals (n=68), were
      included in this study. The partial least-squares discriminant analysis (PLS-DA)
      model was generated from metabolic profiling data, and the score plots showed a
      significant gender-related difference in patients with MI. Many pathways were
      associated with amino acids and purines; amino acids, acylcarnitines, and purines
      differed significantly between male and female patients with MI. This approach
      could be utilized to observe gender-specific metabolic pattern differences
      between healthy controls and patients with MI.

PMID- 26299525
TI  - The application of electrochemistry to pharmaceutical stability testing-
      comparison with in silico prediction and chemical forced degradation approaches.
AB  - The aim of this study was to evaluate the use of electrochemistry to generate
      oxidative degradation products of a model pharmaceutical compound. The compound
      was oxidized at different potentials using an electrochemical flow-cell fitted
      with a glassy carbon working electrode, a Pd/H2 reference electrode and a
      titanium auxiliary electrode. The oxidative products formed were identified and
      structurally characterized by LC-ESI-MS/MS using a high resolution Q-TOF mass
      spectrometer. Results from electrochemical oxidation using electrolytes of
      different pH were compared to those from chemical oxidation and from accelerated
      stability studies. Additionally, oxidative degradation products predicted using
      an in silico commercially available software were compared to those obtained from
      the various experimental methods. The electrochemical approach proved to be
      useful as an oxidative stress test as all of the final oxidation products
      observed under accelerated stability studies could be generated; previously
      reported reactive intermediate species were not observed most likely because the
      electrochemical mechanism differs from the oxidative pathway followed under
      accelerated stability conditions. In comparison to chemical degradation tests
      electrochemical degradation has the advantage of being much faster and does not
      require the use of strong oxidizing agents. Moreover, it enables the study of
      different operating parameters in short periods of time and optimisation of the
      reaction conditions (pH and applied potential) to achieve different oxidative
      products mixtures. This technique may prove useful as a stress test condition for
      the generation of oxidative degradation products and may help accelerate
      structure elucidation and development of stability indicating analytical methods.

PMID- 26299526
TI  - Avoid the perils of using rounded data.
AB  - From a purely technical point of view it is always better to work with
      recorded/unrounded data. This paper discusses reasons why despite this, rounded
      data used for reporting may have been used in the past in calculations and
      visualisation. If rounded data are used then it is recommended that a risk
      assessment of the impact of the rounding is performed. If it is not possible to
      use unrounded data (with many decimal places) then the authors recommend that the
      data used should have at least two decimal places more than the number of decimal
      places required in the reported value ("effectively unrounded data"). Examples
      are given to illustrate the importance of using effectively unrounded data in
      visualisation and numerical calculations. It is recommended that effectively
      unrounded data and, if required, reported data are listed in reports. The
      implications of using rounded data when making formal assessments against
      specification limits is also discussed and guidance is provided on the use of
      nominal and effective specification limits.

PMID- 26299527
TI  - A validated method for the quantification of fosfomycin on dried plasma spots by
      HPLC-MS/MS: application to a pilot pharmacokinetic study in humans.
AB  - Quantification of fosfomycin in the plasma samples of patients is the basis of
      clinical pharmacokinetic studies from which evidence based dosing regimens can be
      devised to maximise antibiotic effectiveness against a pathogen. We have
      developed and validated a LC-MS/MS method to quantify fosfomycin using dried
      plasma spot sampling. Following HILIC chromatography, fosfomycin and
      ethylphosphonic acid, used as internal standard, were measured using negative-ion
      multiple reaction monitoring. The method was linear over the calibration range of
      5-2000mg/L of fosfomycin. Intra-day assay results for dried plasma spot quality
      control samples at 15.6, 79.9 and 1581mg/L of fosfomycin had precision of +/-4.2,
      8.2, and 2.0%, respectively, and accuracy of +3.9, -0.1, and -1.2%, respectively.
      Recovery of fosfomycin from dried plasma spots was calculated as 83.6% and the
      dried plasma spot samples were found to be stable stored at room temperature for
      three months and when stored for four hours at 50 degrees C. A Bland-Altman plot
      comparing DPS to plasma sampling found a negative bias of 16.6%, with all but one
      sample within the mean limits of agreement (-2.6 to 30.6%). Dried plasma spot
      sampling provides a useful tool for pharmacokinetic research of fosfomycin.

PMID- 26299529
TI  - Endoscopic findings of atypical juvenile colonic polyps.

PMID- 26299528
TI  - Dabigatran-induced asymptomatic esophageal mucosal injury.

PMID- 26299530
TI  - Novel EUS-guided double-balloon-occluded gastrojejunostomy bypass.

PMID- 26299531
TI  - ERCP with balloon-overtube-assisted enteroscopy in postsurgical anatomy.

PMID- 26299532
TI  - Anti-obesity activity of the water extract of Lactobacillus paracasei subsp.
      paracasei NTU 101 fermented soy milk products.
AB  - The anti-obesity activity of the water extract of soy milk fermented with
      Lactobacillus paracasei subsp. paracasei NTU 101 (W101) was investigated. A high
      fat diet (HFD) was used to induce obesity in rats, and the effects of daily W101
      feeding (8 weeks) were observed. The rats fed the HFD and supplemented with low
      dose W101 (LW101, 15 mg per kg body weight per day) or high-dose W101 (HW101, 150
      mg per kg body weight per day) had significantly reduced final body weight in
      comparison with that of the HFD group. W101 decreased the formation of lipid
      plaques in the aorta, reduced the adipocyte cross-sectional area and diameter,
      and reduced the levels of CCAAT/enhancer-binding protein beta (C/EBPbeta),
      peroxisome proliferator associated receptor gamma (PPARgamma), and C/EBPalpha.
      Regarding lipogenesis regulation in adipocytes, W101 suppressed heparin
      releasable lipoprotein lipase (HR-LPL) in adipose tissues and inhibited lipid
      absorption, thereby reducing lipogenesis. Lactobacillus paracasei subsp.
      paracasei NTU 101-fermented soy milk may be used to develop health foods that
      prevent obesity. 

PMID- 26299533
TI  - Limbal Stem Cell Transplantation for Soft Contact Lens Wear-Related Limbal Stem
      Cell Deficiency.
AB  - PURPOSE: To describe the outcomes of limbal stem cell transplantation in eyes
      with limbal stem cell deficiency related to soft contact lens wear. DESIGN:
      Retrospective interventional case series. METHODS: Institutional database search
      at the Cincinnati Eye Institute revealed 9 patients (14 eyes) who underwent
      limbal stem cell transplantation with systemic immunosuppression for soft contact
      lens wear-related limbal stem cell deficiency. Outcome measures included patient
      demographics, symptoms, best-corrected visual acuity, ocular surface stability,
      adverse events, and additional surgeries required. RESULTS: Average patient age
      at time of surgery was 46.6 +/- 11.1 years (range 20-60 years). Average duration
      of follow-up was 28 +/- 19.1 months (range 12-70 months). Preoperative best
      corrected visual acuity (BCVA) was 20/40 or worse in all eyes (average 20/70,
      range 20/40-20/250) and patient symptoms included foreign body sensation,
      tearing, redness, and/or pain. Four eyes (29%) underwent living-related
      conjunctival limbal allograft and 10 eyes (71%) underwent cadaver-donor
      keratolimbal allograft surgery. Topical and systemic immunosuppression was used
      in all patients. At final follow-up after limbal stem cell transplantation, there
      was a stable ocular surface in 12 of 14 eyes (86%) and improvement in BCVA to
      20/30 or better and complete resolution of patient symptoms in all except 1
      patient who had significant rosacea blepharokeratoconjunctivitis, whose BCVA
      remained at 20/150 and 20/60, in right and left eyes, respectively. The most
      common adverse event was an increase in intraocular pressure in 8 of 14 eyes
      (57%), requiring topical antiglaucoma treatment. Ten of 14 eyes (71%) underwent
      cataract extraction related to topical steroid use. No eyes required subsequent
      penetrating keratoplasty. CONCLUSION: Limbal stem cell transplantation is a
      viable option for the management of soft contact lens wear-related limbal stem
      cell deficiency in young healthy patients. Early intervention prior to
      subepithelial fibrosis can lead to good visual outcomes with no need for
      subsequent cornea transplant. Co-management with a solid organ transplant
      specialist is helpful for the monitoring and management of systemic adverse
      events related to patient systemic immunosuppression.

PMID- 26299534
TI  - Loculation of Fluid in the Posterior Choroid in Eyes With Central Serous
      Chorioretinopathy.
AB  - PURPOSE: To evaluate potential accumulation of fluid in the outer choroid in eyes
      with central serous chorioretinopathy. DESIGN: Retrospective observational case
      series. METHODS: Patients in 2 community-based retinal practices were evaluated
      for hyporeflective areas in the outer choroid consistent with collections of
      fluid using enhanced depth imaging optical coherence tomography. Eligible
      patients were examined over the preceding 2 years, had a history of central
      serous chorioretinopathy, and did not have a history of choroidal
      neovascularization or photodynamic therapy. RESULTS: In the New York group there
      were 131 eyes of 70 patients who had a mean age of 56.3 (+/- 12.5) years, and 88
      (67.2%) had hyporeflective regions consistent with posterior loculation of fluid
      in the macular region. In the Minnesota data set there were 91 eyes of 48
      patients who had a mean age of 47.9 (+/- 9.9) years and hyporeflective regions
      consistent with posterior loculation of fluid was present in 59 (64.8%). In the
      entire group the mean subfoveal choroidal thickness of those without loculated
      fluid was 344 MUm, as compared with 498 MUm with loculated fluid (P < .001). The
      areas of loculated fluid were hyporeflective, were larger topographically than
      the large choroidal vessels, had an angular inner border, and did not have a
      bounding vascular wall. CONCLUSIONS: Posterior loculation of fluid is a common
      finding in central serous chorioretinopathy, but it has a different pattern and
      distribution than do collections of fluid in the outer choroid and suprachoroidal
      space as seen in other forms of choroidal effusion.

PMID- 26299535
TI  - Association Between Insufficient Photoreceptor Layer Plugging and Postoperative
      Visual Outcome in the Surgically Closed Macular Hole.
AB  - PURPOSE: To investigate whether the photoreceptor layer status of the detached
      retina, which has the potential to plug the macular hole (MH), can predict
      postoperative visual acuity (VA). DESIGN: Retrospective, consecutive,
      observational case series. METHODS: A consecutive series of 48 eyes in 48
      patients with surgically closed MHs were recruited into the study. Spectral
      domain optical coherence tomography (SD OCT) images were obtained preoperatively
      and postoperatively. Length gaps between photoreceptor layers and the
      preoperative diameter of the basal MH in the detached part of the retina was
      calculated for the photoreceptor outer segment (OS) and the external limiting
      membrane (ELM). The postoperative photoreceptor layer status at the fovea,
      including continuity of the ELM line, inner segment ellipsoid line (ISe), and
      cone outer segment tip (COST) line, was categorized by graders. RESULTS: The
      preoperative OS gap length and ELM gap length correlated significantly with
      postoperative VA. A larger OS or ELM gap length was associated with a more severe
      postoperative photoreceptor layer status. Eyes with a moderately reflective
      lesion had a significantly longer OS gap length and ELM gap length, significantly
      worse postoperative VA, and more severe photoreceptor layer status than did eyes
      without such a moderately reflective lesion. Eyes with a better postoperative
      COST status had significantly better postoperative VA (P = .0465). CONCLUSIONS:
      OS and ELM gap length, which represent the degree of insufficiency of MH
      plugging, was strongly correlated with postoperative VA; moreover, these
      preoperative parameters were associated with the postoperative photoreceptor
      layer status, including glial cell proliferation.

PMID- 26299536
TI  - The Small-Aperture IC-8 Intraocular Lens: A New Concept for Added Depth of Focus
      in Cataract Patients.
AB  - PURPOSE: To evaluate visual performance of subjects implanted monocularly with a
      small-aperture hydrophobic intraocular lens (IC-8 IOL). DESIGN: A prospective,
      noncomparative, multicenter case series. METHODS: A series of 12 patients,
      presenting for cataract surgery, were implanted monocularly with a single-piece
      hydrophobic acrylic intraocular with a centrally located opaque annular mask
      measuring 3.23 mm in total diameter with a 1.36 mm central aperture. Uncorrected
      distance, intermediate, and near visual acuities (UDVA, UIVA, and UNVA); depth of
      focus; and subjective symptoms were evaluated for 12 months after implantation.
      Mean +/- standard deviation visual acuity is reported in logMAR. RESULTS: The
      mean monocular UDVA, UIVA, and UNVA improved significantly from 0.42 +/- 0.18,
      0.52 +/- 0.22 and 0.66 +/- 0.23 preoperatively to 0.06 +/- 0.08 (P < .0001), 0.07
      +/- 0.11 (P < .0001), and 0.11 +/- 0.15 (P < .0001) at 1 month, respectively, and
      remained stable until 12 months. At 12 months, 100%, 100%, and 92% of patients
      achieved 20/32 or better binocularly for UDVA, UIVA, and UNVA, respectively. One
      hundred percent of eyes maintained 20/40 or better visual acuity over a range of
      +0.50 diopter to -1.50 diopters of defocus. Subjects implanted with the IC-8 IOL
      perceived a small magnitude of visual symptoms and rated their symptoms on the
      lower end of the severity scale. CONCLUSION: Early results demonstrate that
      monocular IC-8 intraocular lens implantation provides a continuous, broad range
      of vision and excellent acuity across all focal distances.

PMID- 26299537
TI  - Assessment of Anterior, Posterior, and Total Central Corneal Astigmatism in Eyes
      With Keratoconus.
AB  - PURPOSE: To investigate the magnitudes and the axis orientations of anterior,
      posterior, and total central corneal astigmatism in eyes with keratoconus.
      DESIGN: Retrospective case series. METHODS: This study comprised 137 eyes of 137
      keratoconic patients (97 men and 40 women; mean age +/- standard deviation, 36.9
      +/- 12.2 years). The magnitude and the axis orientation of each corneal
      astigmatism were determined with a rotating Scheimpflug system. RESULTS: The mean
      magnitudes of anterior, posterior, and total central corneal astigmatism were
      3.93 +/- 2.74 diopters (D), 0.93 +/- 0.64 D, and 3.90 +/- 2.75 D, respectively.
      With-the-rule (WTR), against-the-rule (ATR), and oblique astigmatism of the
      anterior corneal surface was found in 90 eyes (65.7%), 33 eyes (24.1%), and 14
      eyes (10.2%), respectively, whereas the corresponding astigmatism of the
      posterior corneal surface was found in 14 eyes (10.2%), 15 eyes (10.9%), and 108
      eyes (78.8%), respectively. We found a significant correlation between the
      magnitudes of anterior and posterior corneal astigmatism (Pearson correlation
      coefficient r = 0.769, P < .001). CONCLUSIONS: The mean magnitudes of anterior
      and posterior corneal astigmatism were approximately 4 D and 1 D, respectively,
      in eyes with keratoconus. Approximately 65% and 80% of eyes showed that WTR
      anterior astigmatism and ATR posterior astigmatism, respectively. The presence of
      posterior corneal astigmatism is not necessarily negligible for the accurate
      astigmatic correction of toric intraocular lens implantation or rigid gas
      permeable contact lens wear for keratoconus.

PMID- 26299538
TI  - Clinical Features and Outcomes of Retained Lens Fragments in the Anterior Chamber
      After Phacoemulsification.
AB  - PURPOSE: To review the clinical features, treatments, and outcomes of patients
      with retained lens fragments in the anterior chamber after phacoemulsification
      with an intact posterior capsule. DESIGN: Retrospective, interventional case
      series. METHODS: setting: Duke University Eye Center. STUDY POPULATION: Fifty
      four eyes of 54 patients with a diagnosis of retained lens fragment in the
      anterior chamber following otherwise uncomplicated phacoemulsification cataract
      surgery. Patient demographics, clinical examination findings, ocular biometry
      measurements, treatment received, and pre- and post-lens fragment removal visual
      acuity were recorded. MAIN OUTCOME MEASURES: Corneal edema, time to surgical
      extraction of lens fragment, and visual acuity. RESULTS: All lens fragments were
      located in the inferior angle or the inferior anterior chamber, with 13% of cases
      requiring gonioscopy for diagnosis. Fifty-six percent of eyes had associated
      corneal edema, most often located inferiorly. Forty-four percent of patients were
      initially managed medically, but in all 54 cases the lens fragment was eventually
      removed surgically. The mean time to removal of the lens fragment from the date
      of cataract surgery was 70 days (range 1 day-30 months). Five patients had
      corneal edema that did not resolve following fragment extraction and 3 eventually
      received an endothelial keratoplasty. Best-corrected visual acuity improved from
      an average of 20/51 before lens fragment removal to 20/28 after surgical
      extraction (P < .00001). CONCLUSIONS: Corneal edema is common in the setting of
      retained lens fragments and can evolve to corneal decompensation requiring
      transplantation. Inferior corneal edema, in particular, should alert the
      practitioner to possible retained lens fragment. Surgical removal of retained
      lens fragments should be considered at the time of diagnosis.

PMID- 26299539
TI  - Diversity of bacterial communities in the midgut of Bactrocera cucurbitae
      (Diptera: Tephritidae) populations and their potential use as attractants.
AB  - BACKGROUND: The microbiota plays an important role in insect development and
      fitness. Understanding the gut microbiota composition is essential for the
      development of pest management strategies. Midgut bacteria were isolated from
      nine wild B. cucurbitae populations collected from different agroecological zones
      of India. These isolates were further studied for attractant potential of fruit
      fly adults, and the chemical constituents in the supernatants of gut bacteria
      were analysed. RESULTS: Twenty-six bacterial isolates belonging to the families
      Enterobacteriaceae, Bacillaceae, Micrococcaceae and Staphylococcaceae were
      isolated and identified on the basis of 16S rRNA gene sequence analysis. The
      dominant species in the midgut of melon fly were from the genera Enterobacter
      (34.6%), Klebsiella (19.2%), Citrobacter (7.7%), Bacillus (15.4%) and Providencia
      (7.7%), and 3.8% each of Micrococcus, Staphylococcus, Leclercia and
      Exiguobacterium. Bactrocera cucurbitae and B. dorsalis adults were significantly
      attracted to bacterial whole cell cultures and their supernatants in the fruit
      fly attraction bioassays. Bacillus cereus, Enterobacter, Klebsiella, Citrobacter
      and Providencia species attracted both male and females of Bactrocera species.
      The supernatants of Klebsiella, Citrobacter and Providencia species attracted a
      significantly greater number of females than males. The most abundant chemical
      constituents in supernatants of K. oxytoca and C. freundii were 3-methyl-1
      butanol, 2-phenylethanol, butyl isocyanatoacetate, 2-methyl-1-propanol and 3
      hydroxy-2-butanone, as identified by gas chromatography-mass spectrometry.
      CONCLUSIONS: The bacterial endosymbionts associated with melon fly exhibited
      attractant potential which could facilitate eco-friendly insect control
      strategies. (c) 2015 Society of Chemical Industry.

PMID- 26299540
TI  - Fixed, low radiant exposure vs. incremental radiant exposure approach for diode
      laser hair reduction: a randomized, split axilla, comparative single-blinded
      trial.
AB  - BACKGROUND: Diode lasers are the most commonly used treatment modalities for
      unwanted hair reduction. Only a few controlled clinical trials but not a single
      randomized controlled trial (RCT) compared the impact of various laser
      parameters, especially radiant exposure, onto efficacy, tolerability and safety
      of laser hair reduction. OBJECTIVE: To compare the safety, tolerability and mid
      term efficacy of fixed, low and incremental radiant exposures of diode lasers
      (800 nm) for axillary hair removal, we conducted an intrapatient, left-to-right,
      patient- and assessor-blinded and controlled trial. METHODS: Diode laser (800 nm)
      treatments were evaluated in 39 study participants (skin type II-III) with
      unwanted axillary hairs. Randomization and allocation to split axilla treatments
      were carried out by a web-based randomization tool. Six treatments were performed
      at 4- to 6-week intervals with study subjects blinded to the type of treatment.
      Final assessment of hair reduction was conducted 6 months after the last
      treatment by means of blinded 4-point clinical scale using photographs. The
      primary endpoint was reduction in hair growth, and secondary endpoints were
      patient-rated tolerability and satisfaction with the treatment, treatment-related
      pain and adverse effects. RESULTS: Excellent reduction in axillary hairs (>= 76%)
      at 6-month follow-up visit after receiving fixed, low and incremental radiant
      exposure diode laser treatments was obtained in 59% and 67% of study participants
      respectively (Z value: 1.342, P = 0.180). Patients reported lower visual analogue
      scale (VAS) pain score on the fixed (4.26) than on the incremental radiant
      exposure side (5.64) (P < 0.0003). The only side-effect was mild and transient
      erythema. Subjects better tolerated the fixed, low radiant exposure protocol (P =
      0.03). The majority of the study participants were satisfied with both
      treatments. CONCLUSION: Both low and incremental radiant exposures produced
      similar hair reduction and high and comparable patient satisfaction. However, low
      radiant exposure diode laser treatments were less painful and better tolerated.

PMID- 26299541
TI  - [Not Available].

PMID- 26299542
TI  - [Not Available].

PMID- 26299543
TI  - [Not Available].

PMID- 26299544
TI  - [Not Available].

PMID- 26299545
TI  - How directional change in reading/writing habits relates to directional change in
      displayed pictures.
AB  - It has been suggested that reading/writing habits may influence the appreciation
      of pictures. For example, people who read and write in a rightward direction have
      an aesthetic preference for pictures that face rightward over pictures that face
      leftward, and vice versa. However, correlations for this phenomenon have only
      been found in cross-cultural studies. Will a directional change in
      reading/writing habits within a culture relate to changes in picture preference?
      Korea is a good place to research this question because the country underwent
      gradual changes in reading/writing direction habits, from leftward to rightward,
      during the 20th century. In this study, we analyzed the direction of drawings and
      photos published in the two oldest newspapers in Korea from 1920-2013. The
      results show that the direction of the drawings underwent a clear shift from the
      left to the right, but the direction of the photos did not change. This finding
      suggests a close psychological link between the habits of reading/writing and
      drawing that cannot be accounted for simply by an accidental correspondence
      across different cultures. 

PMID- 26299546
TI  - Rapid evolution of elaborate male coloration is driven by visual system in
      Australian fairy-wrens (Maluridae).
AB  - The interplay between colour vision and animal signalling is of keen interest to
      behavioural ecologists and evolutionary biologists alike, but is difficult to
      address in terrestrial animals. Unlike most avian lineages, in which colour
      vision is relatively invariant among species, the fairy-wrens and allies
      (Maluridae) show a recent gain of ultraviolet sensitivity (UVS). Here, we compare
      the rates of colour evolution on 11 patches for males and females across
      Maluridae in the context of their visual system. We measured reflectance spectra
      for 24 species, estimating five vision-independent colour metrics as well as
      metrics of colour contrast among patches and sexual dichromatism in a receiver
      neutral colour space. We fit Brownian motion (BM) and Ornstein-Uhlenbeck (OU)
      models to estimate evolutionary rates for these metrics and to test whether male
      coloration, female coloration or dichromatism was driven by selective regimes
      defined by visual system or geography. We found that in general male coloration
      evolved rapidly in comparison with females. Male colour contrast was strongly
      correlated with visual system and expanded greatly in UVS lineages, whereas
      female coloration was weakly associated with geography (Australia vs. Papua New
      Guinea). These results suggest that dichromatism has evolved in Maluridae as
      males and females evolve at different rates, and are driven by different
      selection pressures. 

PMID- 26299547
TI  - Experimental assessment of social interactions in two species of the genus
      Teratoscincus (Gekkota).
AB  - Social organization of many reptile species that are rare in the wild remains
      rather unexplored due to difficulties when setting experiments in the field.
      Behavioral analysis of standard social situations in laboratory conditions is
      considered an indirect method to reveal social behavior in the field. We studied
      two rare species of geckos, Teratoscincus scincus and Teratoscincus keyserlingii,
      inhabiting sand dunes of Uzbekistan and Eastern Iran. A series of experiments was
      carried out to quantify responses in social interactions among conspecific adults
      as well as reactions of these towards conspecific/heterospecific subadults and
      juveniles. We also assessed the effect of species and sex on recorded behavior.
      Finally, the reaction to threat stimuli simulating predator attack was analyzed.
      The species effect was recorded only in the response to a simulated predatory
      attack: T. scincus typically escaped whereas larger T. keyserlingii attacked the
      stimulus. In accordance with the sexual competition hypothesis, agonistic
      interactions were nearly exclusively confined to male-male encounters while
      females were tolerant to each other. Male-female encounters regularly resulted in
      mating attempts, which suggests that females are not strongly selective in
      choosing partners. Therefore, male aggression can be linked to mate guarding or
      territoriality. Adults' lack of interest in immature geckos may indicate
      generalized tolerance of adults towards young. 

PMID- 26299548
TI  - An alternative to the stay/switch equation assessed when using a changeover
      delay.
AB  - An alternative to the generalized matching equation for understanding concurrent
      performances is the stay/switch model. For the stay/switch model, the important
      events are the contingencies and behaviors at each alternative. The current
      experiment compares the descriptions by two stay/switch equations, the original,
      empirically derived stay/switch equation and a more theoretically derived
      equation based on ratios of stay to switch responses matching ratios of stay to
      switch reinforcers. The present experiment compared descriptions by the original
      stay/switch equation when using and not using a changeover delay. It also
      compared descriptions by the more theoretical equation with and without a
      changeover delay. Finally, it compared descriptions of the concurrent
      performances by these two equations. Rats were trained in 15 conditions on
      identical concurrent random-interval schedules in each component of a multiple
      schedule. A COD operated in only one component. There were no consistent
      differences in the variance accounted for by each equation of concurrent
      performances whether or not a COD was used. The simpler equation found greater
      sensitivity to stay than to switch reinforcers. It also found a COD eliminated
      the influence of switch reinforcers. Because estimates of parameters were more
      meaningful when using the more theoretical stay/switch equation it is preferred. 

PMID- 26299549
TI  - Elevated IL-3 and IL-12p40 levels in the lower airway of infants with RSV-induced
      bronchiolitis correlate with recurrent wheezing.
AB  - Respiratory Syncytial Virus (RSV) is the first cause of hospitalization due to
      bronchiolitis in infants. RSV bronchiolitis has been linked to asthma and
      recurrent wheezing, however the mechanisms behind this association have not been
      elucidated. Here, we evaluated the cytokine and chemokine profiles in the airways
      in infants with RSV bronchiolitis. Nasopharyngeal Aspirates (NPA) and
      Bronchoalveolar Lavage Fluids (BALF) from infants hospitalized due to RSV
      bronchiolitis and healthy controls were analyzed for cytokine and chemokine
      production. We observed elevated levels of Th2 cytokines (IL-3, IL-4, IL-10 and
      IL-13), pro-inflammatory cytokines and chemokines (IL-1beta, IL-6, TNF-beta, MCP
      1/CCL2, MIP-1alpha/CCL3 and IL-8/CXCL8) in BALF from infants with RSV
      bronchiolitis, as compared to controls. We found a direct correlation of IL-3 and
      IL-12p40 levels with the development of recurrent wheezing later in life. These
      results suggest that IL-3 and IL-12p40 could be considered as molecular
      predictors for recurrent wheezing due to RSV infection. 

PMID- 26299550
TI  - Sedation for transesophageal echocardiography: comparison of propofol, midazolam
      and midazolam-alfentanil combination.
AB  - AIM: The administration of trans esophageal echocardiography (TEE) may cause
      nausea, shortness of breath, agitation, emotional distress and pain in patients
      due to pharyngo-esophageal intubation, which may be partially relieved by
      sedoanalgesia. The aim of this study was to compare clinical effects of
      midazolam, midazolam-alfentanil combination and propofol sedation given for
      sedation and sedoanalgesia to patients with planned diagnostic TEE interventions.
      METHODS: This study was prospectively completed with 90 randomized adult patients
      in ASA risk groups I-II-III. Group M were given 2.5 mg midazolam, group MA were
      given 1 mg midazolam and 5 MUg/kg alfentanil and group P were given 0.5 mg/kg
      propofol intravenous bolus. If necessary, additional doses were administered.
      Patients administered with TEE were evaluated in terms of additional dose
      requirements, Ramsey Sedation Scale (RSS), modified Aldrete Scoring (MAS),
      recovery time and duration of stay in the hospital. RESULTS: In the group P
      additional dose requirements were greater (p<0.05), as well as the duration of
      stay in the recovery unit and hospital were shorter (p<0.05). On insertion of the
      TEE probe, the RSS in the group P was clearly higher than in other groups M and
      MA (p<0.05). CONCLUSION: During the TEE intervention, the use of propofol,
      contrary to requirements for additional dose and observation of apnea, appears to
      be advantageous due to providing more rapid and effective sedation depth without
      a need of expensive antagonist agents, and allowing early discharge of patients.
      Additionally, it seems that the use of midazolam combined with alfentanil, is
      more advantageous comparing to midazolam alone.

PMID- 26299551
TI  - Exploitation of pleiotropic actions of statins by using tumour-targeted delivery
      systems.
AB  - Statins are drugs traditionally used to lower cholesterol levels in blood. At
      concentrations 100- to 500-fold higher than those needed for reaching cholesterol
      lowering activity, they have anti-tumour activity. This anti-tumour activity is
      based on statins pleiotropic effects derived from their ability to inhibit the
      mevalonate synthesis and include anti-proliferative, pro-apoptotic, anti
      angiogenic, anti-inflammatory, anti-metastatic actions and modulatory effects on
      intra-tumour oxidative stress. Thus, in this review, we summarise the possible
      pleiotropic actions of statins involved in tumour growth inhibition. Since the
      administration of these high doses of statins is accompanied by severe side
      effects, targeted delivery of statins seems to be the appropriate strategy for
      efficient application of statins in oncology. Therefore, we also present an
      overview of the current status of targeted delivery systems for statins with
      possible utilisation in oncology. 

PMID- 26299552
TI  - Adolescent and Young Adult Health in the Arab Region: Where We Are and What We
      Must Do.

PMID- 26299553
TI  - Time for an Adolescent Health Surveillance System in Saudi Arabia: Findings From
      "Jeeluna".
AB  - PURPOSE: With the increasing burden of noncommunicable disease, adolescence is
      viewed as an opportune time to prevent the onset of certain behaviors and promote
      healthy states. Although adolescents comprise a considerable portion of Saudi
      Arabia's population, they have received insufficient attention and indicators of
      their health status, as a first step in a prevention cycle are unavailable. This
      study was carried out with the aim of identifying the health risk behaviors and
      health status of adolescents in Saudi Arabia. METHODS: This cross-sectional,
      school-based study was carried out in all 13 regions of Saudi Arabia. Through
      multistage, cluster, random sampling, intermediate, and secondary school students
      were invited to participate. Data were collected by means of a self-administered
      questionnaire addressing health risk behaviors and health status, clinical
      anthropometric measurements, and laboratory investigations. RESULTS: A total of
      12,575 adolescents participated. Various health risk behaviors, including dietary
      and sedentary behaviors, lack of safety measures, tobacco use, bullying, and
      violence were highly prevalent. Twenty-eight percent of adolescents reported
      having a chronic health condition, 14.3% reported having symptoms suggestive of
      depression, 30.0% were overweight/obese, and 95.6% were vitamin D deficient.
      CONCLUSION: Behaviors and conditions known to persist into adulthood and result
      in morbidity and premature mortality are prevalent among adolescents in Saudi
      Arabia. Preventive measures and local health policies are urgently needed and can
      impact adolescents and future adults. Establishing adolescent health surveillance
      is necessary to monitor trends and impacts of such measures.

PMID- 26299554
TI  - Weight Changes After Reduction Mammaplasty in Adolescents.
AB  - PURPOSE: The ability to exercise more easily and weight loss are often cited
      benefits of reduction mammaplasty. However, measured weight outcomes after this
      common procedure are lacking. The purpose of this study was to measure body mass
      index (BMI) changes in an otherwise healthy adolescent sample after bilateral
      breast reduction. METHODS: We retrospectively reviewed the records of patients
      aged 12-21 years who underwent reduction mammaplasty at our institution between
      2007 and 2013, with a minimum postoperative follow-up time of 1 year. Charts were
      reviewed for preoperative and postoperative height and weight, amount of breast
      tissue resected, and medical comorbidities. No formal nutritional support or
      weight loss program was instituted before or after surgery. RESULTS: Eighty
      patients meeting eligibility criteria were identified. The mean follow-up time
      was 2.0 +/- 1.0 years. Mean postoperative BMI did not differ significantly from
      mean preoperative BMI (27.8 +/- 7.1 kg/m(2) vs. 27.3 +/- 6.4 kg/m(2)). However,
      among overweight and obese patients, a significant gain in preoperative to
      postoperative BMI was observed, on average (p = .019). Twelve (22.2%) of these
      patients increased their BMI by at least 10% after reduction mammaplasty.
      Although approximately one third (37%) of overweight/obese patients decreased
      their BMI, only 5.6% decreased BMI by at least 10%. CONCLUSIONS: We found no
      significant difference between mean preoperative and postoperative BMI among
      patients who underwent reduction mammaplasty. Our results suggest that although
      reduction mammaplasty may facilitate exercise and help some patients lose weight,
      meaningful postoperative weight loss without additional support is rare.

PMID- 26299555
TI  - Development and Validation of the Adolescent Assessment of Preparation for
      Transition: A Novel Patient Experience Measure.
AB  - PURPOSE: Significant gaps exist in health care transition (HCT) preparation that
      can impact care and outcomes in young adults with chronic illness. No quality
      measure exists to directly assess adolescent experiences of HCT preparation. Our
      objective was to develop an adolescent-reported measure of the quality of HCT
      preparation received from pediatric health care providers. METHODS: The
      Adolescent Assessment of Preparation for Transition (ADAPT) is a 26-item mailed
      survey designed for completion by 16- and 17-year-old adolescents with a chronic
      health condition. Adolescents from three samples (two large Medicaid insurance
      plans [n = 3,000 each] and one large tertiary care pediatric hospital [n = 623])
      were mailed the survey. An iterative developmental process included focus groups
      and cognitive interviews, and validity was assessed using confirmatory factor
      analysis and ordinal reliability coefficients. RESULTS: Reliability and validity
      was evaluated for the following three prespecified composite measures: (1)
      counseling on transition self-management; (2) counseling on prescription
      medication; and (3) transfer planning. Across the three samples, all but one
      measure had good internal consistency (ordinal reliability coefficient >= .7).
      Confirmatory factor analysis using tetrachoric correlation coefficients was
      stable across samples and supported the construct validity of the first two
      composite measures. CONCLUSIONS: ADAPT is a reliable, validated instrument
      measuring the quality of HCT preparation experiences reported by adolescents with
      chronic disease. ADAPT will enable clinical programs and health care delivery
      systems to assess the quality of HCT preparation and provide targets for
      improvement in adolescent counseling related to transition.

PMID- 26299556
TI  - Improving the Quality of Health Care Services for Adolescents, Globally: A
      Standards-Driven Approach.
AB  - PURPOSE: The World Health Organization (WHO) undertook an extensive and elaborate
      process to develop eight Global Standards to improve quality of health care
      services for adolescents. The objectives of this article are to present the
      Global Standards and their method of development. METHODS: The Global Standards
      were developed through a four-stage process: (1) conducting needs assessment; (2)
      developing the Global Standards and their criteria; (3) expert consultations; and
      (4) assessing their usability. Needs assessment involved conducting a meta-review
      of systematic reviews and two online global surveys in 2013, one with primary
      health care providers and another with adolescents. The Global Standards were
      developed based on the needs assessment in conjunction with analysis of 26
      national standards from 25 countries. The final document was reviewed by experts
      from the World Health Organization regional and country offices, governments,
      academia, nongovernmental organizations, and development partners. The standards
      were subsequently tested in Benin and in a regional expert consultation of Latin
      America and Caribbean countries for their usability. RESULTS: The process
      resulted in the development of eight Global Standards and 79 criteria for
      measuring them: (1) adolescents' health literacy; (2) community support; (3)
      appropriate package of services; (4) providers' competencies; (5) facility
      characteristics; (6) equity and nondiscrimination; (7) data and quality
      improvement; and (8) adolescents' participation. CONCLUSIONS: The eight standards
      are intended to act as benchmarks against which quality of health care provided
      to adolescents could be compared. Health care services can use the standards as
      part of their internal quality assurance mechanisms or as part of an external
      accreditation process.

PMID- 26299557
TI  - Parent Preferences for Communicating With Their Adolescent's Provider Using New
      Technologies.
AB  - PURPOSE: Because adolescents make few health care visits, we assessed the views
      of parents of adolescents on various means to communicate with their adolescents'
      physicians about vaccine reminders and appointments, medication refills and test
      results-including phone, mail, e-mail, text messages, and personal health records
      (PHRs). METHODS: We performed a cross-sectional survey of 400 parents of
      adolescents presenting to four pediatric offices (two urban, two suburban) in
      Rochester, NY in 2011 before vaccine reminders occurring in these practices.
      RESULTS: Roughly half of parents (60% urban, 52% suburban, p = .11) were
      accepting of teens receiving their own vaccine reminders. Urban parents preferred
      communicating with the provider via telephone, whereas suburban parents preferred
      e-mail for most issues and a PHR for receipt of test results. In adjusted
      analyses, being younger was associated with preferring text message vaccine
      reminders (41 to <51 years: adjusted relative risk [aRR] = .8, p = .02; >=51
      years, aRR = .5, p < .001), and being a suburban parent was associated with
      preferring e-mail reminders (aRR = 1.6, p < .001). Those who were younger (41 to
      <51 years: aRR = .6, p = .007; >=51 years: aRR = .4, p < .001) and suburban (aRR
      = 2.4, p < .001) were most likely to be interested in general use of a PHR.
      CONCLUSIONS: Our study shows that some, but not all, parents are ready for
      electronic (text message, e-mail, PHR) communications for their adolescents'
      health care and that a parent age and socioeconomic divide exists. Providing
      options in the means in which parents communicate with an adolescent's provider
      is ideal.

PMID- 26299558
TI  - Adolescent Trajectories of Depressive Symptoms: Codevelopment of Behavioral and
      Academic Problems.
AB  - PURPOSE: Increasing evidence suggests the existence of heterogeneity in the
      development of depressive symptoms during adolescence, but little remains known
      regarding the implications of this heterogeneity for the development of commonly
      co-occurring problems. In this study, we derived trajectories of depressive
      symptoms in adolescents and examined the codevelopment of multiple behavioral and
      academic problems in these trajectories. METHODS: Participants were 6,910
      students from secondary schools primarily located in disadvantaged areas of
      Quebec (Canada) who were assessed annually from the age 12 to 16 years.
      Trajectories were identified using growth mixture modeling. The course of
      behavioral (delinquency, substance use) and academic adjustment (school liking,
      academic achievement) in trajectories was examined by deriving latent growth
      curves for each covariate conditional on trajectory membership. RESULTS: We
      identified five trajectories of stable-low (68.1%), increasing (12.1%),
      decreasing (8.7%), transient (8.7%), and stable-high (2.4%) depressive symptoms.
      Examination of conditional latent growth curves revealed that the course of
      behavioral and academic problems closely mirrored the course of depressive
      symptoms in each trajectory. CONCLUSIONS: This pattern of results suggests that
      the course of depressive symptoms and other adjustment problems over time is
      likely to involve an important contribution of shared underlying developmental
      process(es).

PMID- 26299559
TI  - Substance Use Disorder Counselors' Reports of Tobacco Cessation Services
      Availability, Implementation, and Tobacco-related Knowledge.
AB  - PURPOSE: Adolescence is a prime developmental stage for early tobacco cessation
      (TC) intervention. This study examined substance use disorder counselors' reports
      of the availability and implementation of TC services (behavioral treatments and
      pharmacotherapies) in their treatment programs and the relationship between their
      tobacco-related knowledge and implementation of TC services. METHODS: Survey data
      were collected in 2012 from 63 counselors working in 22 adolescent-only treatment
      programs. Measures included 15 TC behavioral treatments, nine TC
      pharmacotherapies, and three tobacco-related knowledge scales
      (morbidity/mortality, modalities and effectiveness, pharmacology). RESULTS:
      First, nine of the 15 behavioral treatments are reported as being available by
      more than half of counselors; four of the 15 behavioral treatments are used by
      counselors with more than half of adolescents. Of the nine pharmacotherapies,
      availability of the nicotine patch is reported by almost 40%, buproprion by
      nearly 30%, and clonidine by about 21% of counselors. Pharmacotherapies are used
      by counselors with very few adolescents. Second, counselors' tobacco-related
      knowledge varies based on the knowledge scale examined. Third, we only find a
      significant positive relationship between counselors' implementation of TC
      behavioral treatments and TC modalities and effectiveness knowledge. DISCUSSION:
      Findings suggest that more behavioral treatments should be made available in
      substance use disorder treatment programs considering that they are the main
      treatment recommendation for adolescents. Counselors should be encouraged to
      routinely use a wide range of available behavioral treatments. Finally,
      counselors should be encouraged to expand their knowledge of TC modalities and
      effectiveness because of the relationship with behavioral treatments
      implementation.

PMID- 26299560
TI  - Factors Associated With Early Sexual Experience Among American Indian and Alaska
      Native Youth.
AB  - PURPOSE: American Indian and Alaska Native (AI/AN) youth experience disparities
      associated with sexual and reproductive health, including early age of sexual
      initiation. Identifying factors that are most proximally related to early sexual
      intercourse and that are modifiable through health promotion interventions may
      help to reduce these disparities. Using a multisystem approach, we assessed
      individual (biological, psychological, and behavioral), familial, and
      extrafamilial (peer behavioral) factors associated with lifetime sexual
      experience among AI/AN early adolescents living in three geographically dispersed
      U.S. regions. METHODS: We analyzed cross-sectional data from 537 AI/AN youth aged
      12-14 years, recruited from 27 study sites in Alaska, Arizona, and the Pacific
      Northwest. We used multilevel logistic regression models to estimate associations
      between independent variables and lifetime sexual intercourse (oral and/or
      vaginal sex) individually, within discrete systems, and across systems. RESULTS:
      The analytical sample was 55.1% female, with a mean age of 13.2 years (standard
      deviation = 1.06 years); 6.5% were sexually experienced. In the final model, we
      found that lower next-year intentions to have oral or vaginal sex (psychological
      factors), avoidance of risky situations, and nonuse of alcohol (behavioral
      factors) were associated with lower odds of lifetime sexual intercourse (all p <=
      .01). No other variables were significantly associated with lifetime sexual
      intercourse. CONCLUSIONS: Interventions that reduce sexual intentions, exposure
      to risky situations, and alcohol use may help to delay sexual initiation among
      AI/AN early adolescents.

PMID- 26299561
TI  - Early Childhood Maltreatment and Girls' Sexual Behavior: The Mediating Role of
      Pubertal Timing.
AB  - PURPOSE: Although links between early childhood maltreatment and girls' sexual
      behavior in adolescence have been well established, it is unclear whether
      different forms of maltreatment are differentially associated with sexual
      outcomes and whether distinct mechanisms explain associations across maltreatment
      types. METHODS: Using data from National Longitudinal Study of Adolescent Health
      (Add Health), the present study examines whether physical abuse, sexual abuse,
      and physical neglect in early childhood differentially predict girls' age at
      first intercourse and number of sexual partners in early adulthood. The study
      also tests whether early pubertal timing mediates the link between early
      maltreatment and sexual behavior (N = 6,364). RESULTS: Findings indicate that
      early sexual and physical abuse were equally predictive of earlier age at first
      intercourse and a greater number of sexual partners, but that only the sexual
      abuse-age at first intercourse link was mediated by early puberty. CONCLUSIONS:
      These results suggest that sexual abuse and physical abuse are associated with
      earlier and riskier sexual behavior in girls relative to no maltreatment and to
      similar degrees. However, only the link between sexual abuse and sexual behavior
      involves a biological mechanism manifested in early pubertal timing.

PMID- 26299562
TI  - Variation in Practice of Expedited Partner Therapy for Adolescents by State
      Policy Environment.
AB  - PURPOSE: The purpose of this study was to assess provider practice of expedited
      partner therapy (EPT) for adolescents with chlamydial infection across varying
      state policy environments and compare provider practice in a parallel treatment
      scenario for a nonsexually transmitted disease. METHODS: Anonymous survey of
      randomly selected providers in one of three state EPT policy environments: EPT is
      (A) explicitly legal; (B) permissible, but not directly referenced in law; or (C)
      potentially allowable. RESULTS: Of 195 respondents, only 20% reported ever
      practicing EPT. Group A providers were more likely to have used EPT than Groups B
      and C. Commonly cited barriers included missed opportunity to counsel partners
      and ensuring medication delivery. In parallel hypothetical scenarios, providers
      were more likely to offer prophylactic antibiotics to a patient's mother for
      pertussis exposure without a face-to-face visit than the sexual partner of an
      adolescent with chlamydia. CONCLUSIONS: Further investigation is needed to better
      understand provider and policy factors that may facilitate EPT provision to
      adolescents.

PMID- 26299564
TI  - Inhibition effect of a non-permeating component on gas permeability of nanoporous
      graphene membranes.
AB  - We identify the inhibition effect of a non-permeating gas component on gases
      permeating through the nanoporous graphene membranes and reveal its mechanisms
      from molecular dynamics insights. The membrane separation process involves the
      gas mixtures of CH4/H2 and CH4/N2 with different partial pressures of the non
      permeating gas component (CH4). The results show that the permeance of the H2 and
      N2 molecules decreases sharply in the presence of the CH4 molecules. The
      permeance of the N2 molecules can be reduced to as much as 64.5%. The adsorption
      of the CH4 molecules on the graphene surface weakens the surface adsorption of
      the H2 and N2 molecules due to a competitive mechanism, accordingly reducing the
      permeability of the H2 and N2 molecules. For the N2 molecules with stronger
      adsorption ability, the reduction of the permeance is greater. On the other hand,
      the CH4 molecules near the nanopore have a blocking effect, which further
      inhibits the permeation of the H2 and N2 molecules. In addition, we predict the
      selectivity of the nanopore by using density functional theory calculations. This
      work can provide valuable guidance for the application of nanoporous graphene
      membranes in the separation of the gas mixtures consisting of permeating and non
      permeating components with different adsorption abilities. 

PMID- 26299563
TI  - Psychosocial Well-Being of Adolescents Before and After a 1-Year Telephone-Based
      Adiposity Prevention Study for Families.
AB  - PURPOSE: Body image and psychosocial well-being play an important role in
      influencing health behavior of obese adolescents. Effects of family-based
      interventions on self-image and mental well-being are poorly understood. The
      effects of a parent-delivered intervention on psychosocial well-being in obese
      adolescents were investigated. METHODS: A subset of secondary variables from the
      randomized-controlled Telephone-based Adiposity prevention study For Families
      (T.A.F.F. study) was analyzed. Multivariate analysis of variance and Pearson
      correlations were used to examine intervention effects on measures of body image,
      body dissatisfaction, self-efficacy, self-worth, and resilience and changes of
      standard deviation score of body mass index (BMI-SDS). RESULTS: A total of 154
      randomized adolescents participated in this study (10-17 years). Body
      dissatisfaction decreased between baseline and follow-up (p = .013, confidence
      interval [CI], .03-.29), whereas self-efficacy increased (p = .022; CI, -1.73 to 
      0.14). Both were independent of the randomization arm. Initial body image was a
      negative predictor of self-efficacy after the intervention. Changes in body
      dissatisfaction and self-efficacy were positively correlated with changes in self
      worth and resilience but were not related to changes in weight status.
      CONCLUSIONS: Overweight/obese adolescents have a high level of body
      dissatisfaction, more pronounced in girls than in boys. Interactions within
      families during overweight and obesity interventions need to be investigated in
      relation to adolescent body self-concept.

PMID- 26299566
TI  - Formation of alpha-[KSiH3] by hydrogenolysis of potassium triphenylsilyl.
AB  - Hydrogenation of easily accessible potassium triphenylsilyl [K(Me6TREN)SiPh3]
      gave the hydrogen storage material alpha-[KSiH3] in high yields by an unusual
      hydrogenolytic cleavage of silicon-phenyl bonds. 

PMID- 26299565
TI  - Distribution and effect of steroidal saponin derivative WRC3 in B16 melanoma
      cells.
AB  - Steroidal saponins have recently attracted attention due to their structural
      diversity and significant biological activities, including anti-hyperlipidemic,
      antibacterial, anti-inflammatory, immunomodulatory and anti-HIV activities. In
      the present study, it was demonstrated that WRC3, a novel saponin derivative, can
      inhibit B16 cancer cells by inducing apoptotic cell death with an IC50 value of
      12.09 uM. The inhibitory effect of WRC3 on B16 cells appears to occur in a time-
      and concentration-dependent manner. The fluorescence distribution observed by
      confocal microscopy revealed that WRC3 entered cells and acted in the cytoplasm
      without causing genetic toxicity. Following administration of WRC3 (2.5, 5.0 and
      7.5 g/kg body weight) once a day for 7 days, no obvious abnormalities were
      observed in the organs of the mice as demonstrated by hematoxylin and eosin
      staining. Compared with the normal control group, aspartate transaminase (AST),
      alanine transaminase (ALT), creatine and urea levels in the serum of mice treated
      with WRC3 (2.5-7.5 uM) remained unchanged. In conclusion, it was demonstrated
      that WRC3 can induce cancer cell death without causing genetic toxicity,
      hepatotoxicity or nephrotoxicity.

PMID- 26299567
TI  - Enantioselective and Synergetic Toxicity of Axial Chiral Herbicide Propisochlor
      to SP2/0 Myeloma Cells.
AB  - The axial chiral herbicide propisochlor is used to control weeds. Different
      enantiomers of a compound usually have different biological activities. It is
      unclear how the toxicities of the propisochlor enantiomers differ. Propisochlor
      enantiomers, separated by high-performance liquid chromatography, were tested on
      SP2/0 myeloma cells. Cytotoxicity and apoptosis were measured, and interactions
      between the enantiomers were evaluated. The rac-propisochlor, pure R-(+) isomer,
      and pure S-(-) isomer inhibited cell proliferation and induced apoptosis. The rac
      propisochlor, R-(+) isomer, and S-(-) isomer half maximal effective concentration
      values after 24 h of incubation were 111 +/- 0.15, 68 +/- 0.09, and 99 +/- 0.21
      MUM, respectively. R-(+) isomer induced the most apoptosis. R-(+) isomer was
      ~1.63 times more cytotoxic than rac-propisochlor and ~1.46 times more cytotoxic
      than S-(-) isomer. Antagonistic cytotoxic interactions were found between R-(+)
      and S-(-) isomers. This is the first time the toxicities of these enantiomers and
      antagonism between the enantiomers have been reported. The antagonism indicates
      that the ecotoxicological effects of the enantiomers should be investigated. 

PMID- 26299568
TI  - In vitro assembly of a viral envelope.
AB  - Viruses such as influenza and Ebola are enveloped in lipid bilayers annexed from
      host cells and containing glycoproteins essential for the infection process. At
      the molecular level little is known about the assembly process in terms of
      physical interactions between the lipids and glycoproteins. In this paper we
      assemble HIV glycoproteins in lipid vesicles in order to examine envelope
      assembly, a process that is usually only executed under control of a host cell.
      Using atomic force microscopy it was possible to observe fusion of individual
      envelope like particles, and contrast this with the behaviour of lipid vesicles
      without envelope glycoproteins. It was found that the inclusion of glycoproteins
      caused the vesicles to distort and that the subsequent fusion "footprint" with a
      lipid bilayer was related to the envelopes' unique morphology. This non-spherical
      morphology suggests that the presence of a viral capsid may be essential for the
      stability of an enveloped virus. Interactions between trans-membrane gp41 and
      gp120, the spikes protruding from a virion, were examined using supported lipid
      bilayers. Interactions between the gp120 and membrane-located gp41 resulted in
      the assembly of unusual molecular wires, one molecule in height and with a zigzag
      arrangement of gp120 molecules. In this work we have shown that purely
      physical/chemical interactions have dramatic effects on glycoprotein/lipid
      assembly and should be considered in the development of virus based technologies
      such as virosomes. 

PMID- 26299569
TI  - Potential application of injectable chitosan hydrogel treated with siRNA in
      chronic rhinosinusitis therapy.
AB  - Chronic rhinosinusitis is a condition with severe clinical symptoms and limited
      therapeutic solutions. It has been reported that vascular endothelial growth
      factor (VEGF) can promote nasal epithelial cell growth and result in hyperplasia
      of the sinuses. Therefore, the downregulation of VEGF may inhibit the process of
      hyperplasia. In the present study, small interfering RNA (siRNA) targeting VEGF
      was used to silence the expression of VEGF, and injectable chitosan based
      hydrogel, which is suitable for sinus injection and exhibits long-term retention,
      was prepared as the siRNA carrier. Human bronchial epithelial cells were cultured
      directly on the hydrogel to observe the biological performance in vitro. Further
      in vivo effects were investigated by the injection of the hydrogel into the sinus
      cavity. Following the introduction of siRNA introducing, the expression of VEGF
      in the bronchial epithelial cells was significantly suppressed at mRNA and
      protein levels. The number of living cells on the gel was significantly
      decreased, thus resulting in the inhibition of proliferation. However, the
      cytoskeletal arrangement of the remaining cells were not affected substantially.
      The hydrogel was able to retain the siRNA for an extended duration, which enabled
      a sustained supply of siRNA. The in vivo sinus mucosa analysis revealed that the
      siRNA was able to collocate with cells and the mucosa thickness was substantially
      decreased. In conclusion, the results of the present study suggested that
      injectable chitosan based hydrogel, treated with siRNA targeting VEGF, may be
      used as a convenient therapeutic option for chronic rhinosinusitis.

PMID- 26299570
TI  - Does the American College of Surgeons NSQIP-Pediatric Accurately Represent
      Overall Patient Outcomes?
AB  - BACKGROUND: The National Surgical Quality Improvement Program-Pediatrics (NSQIP
      P) collects data for institutional quality benchmarking of surgery performed on
      children using a sampling algorithm. The Pediatric and Infant Case Log and
      Outcomes (PICaLO) is a database of all general and thoracic pediatric surgery
      (GTPS) procedures performed at our institution with the attendant complications.
      This study compared postsurgical occurrences in a NSQIP-P sample with all
      postoperative occurrences at a single institution to test the hypothesis that a
      sample of higher risk procedures represents the actual event rate for all higher
      risk procedures. STUDY DESIGN: The definitions of postoperative occurrences used
      in PICaLO are derived from NSQIP-P but tracked past 30 days postoperatively and
      include additional occurrences (ie, anastomotic leak). The number and types of
      occurrences and number of deaths from PICaLO and NSQIP-P databases were compared
      for procedures specific to pediatric GTPS procedures during 2012 to 2013. A chi
      square test evaluated the proportion of occurrences and deaths in PICaLO to NSQIP
      P. RESULTS: The NSQIP-P sampled 37.7% of eligible GTS procedures recorded in
      PICaLO during the study period. The proportion of cases with 1 or more
      occurrences was significantly higher in the NSQIP-P dataset when compared with
      all cases in PICaLO (p < 0.0001). When NSQIP-P and PICaLO were compared based on
      specific CPT codes, NSQIP-P still had a higher event rate (p = 0.004).
      CONCLUSIONS: In focused comparisons, the data demonstrate that the NSQIP-P
      sampling algorithm successfully identifies CPT codes with higher postoperative
      event rates than the overall cohort of pediatric GTPS patients, but may not be
      reflective of the total experience for procedures with those CPT codes.

PMID- 26299571
TI  - Single-Cell RNA-Seq with Waterfall Reveals Molecular Cascades underlying Adult
      Neurogenesis.
AB  - Somatic stem cells contribute to tissue ontogenesis, homeostasis, and
      regeneration through sequential processes. Systematic molecular analysis of stem
      cell behavior is challenging because classic approaches cannot resolve cellular
      heterogeneity or capture developmental dynamics. Here we provide a comprehensive
      resource of single-cell transcriptomes of adult hippocampal quiescent neural stem
      cells (qNSCs) and their immediate progeny. We further developed Waterfall, a
      bioinformatic pipeline, to statistically quantify singe-cell gene expression
      along a de novo reconstructed continuous developmental trajectory. Our study
      reveals molecular signatures of adult qNSCs, characterized by active niche
      signaling integration and low protein translation capacity. Our analyses further
      delineate molecular cascades underlying qNSC activation and neurogenesis
      initiation, exemplified by decreased extrinsic signaling capacity, primed
      translational machinery, and regulatory switches in transcription factors,
      metabolism, and energy sources. Our study reveals the molecular continuum
      underlying adult neurogenesis and illustrates how Waterfall can be used for
      single-cell omics analyses of various continuous biological processes. 

PMID- 26299572
TI  - Humanized Mice Reveal Differential Immunogenicity of Cells Derived from
      Autologous Induced Pluripotent Stem Cells.
AB  - The breakthrough of induced pluripotent stem cell (iPSC) technology has raised
      the possibility that patient-specific iPSCs may become a renewable source of
      autologous cells for cell therapy without the concern of immune rejection.
      However, the immunogenicity of autologous human iPSC (hiPSC)-derived cells is not
      well understood. Using a humanized mouse model (denoted Hu-mice) reconstituted
      with a functional human immune system, we demonstrate that most teratomas formed
      by autologous integration-free hiPSCs exhibit local infiltration of antigen
      specific T cells and associated tissue necrosis, indicating immune rejection of
      certain hiPSC-derived cells. In this context, autologous hiPSC-derived smooth
      muscle cells (SMCs) appear to be highly immunogenic, while autologous hiPSC
      derived retinal pigment epithelial (RPE) cells are immune tolerated even in non
      ocular locations. This differential immunogenicity is due in part to abnormal
      expression of immunogenic antigens in hiPSC-derived SMCs, but not in hiPSC
      derived RPEs. These findings support the feasibility of developing hiPSC-derived
      RPEs for treating macular degeneration. 

PMID- 26299573
TI  - Inflammation-Induced Emergency Megakaryopoiesis Driven by Hematopoietic Stem Cell
      like Megakaryocyte Progenitors.
AB  - Infections are associated with extensive platelet consumption, representing a
      high risk for health. However, the mechanism coordinating the rapid regeneration
      of the platelet pool during such stress conditions remains unclear. Here, we
      report that the phenotypic hematopoietic stem cell (HSC) compartment contains
      stem-like megakaryocyte-committed progenitors (SL-MkPs), a cell population that
      shares many features with multipotent HSCs and serves as a lineage-restricted
      emergency pool for inflammatory insults. During homeostasis, SL-MkPs are
      maintained in a primed but quiescent state, thus contributing little to steady
      state megakaryopoiesis. Even though lineage-specific megakaryocyte transcripts
      are expressed, protein synthesis is suppressed. In response to acute
      inflammation, SL-MkPs become activated, resulting in megakaryocyte protein
      production from pre-existing transcripts and a maturation of SL-MkPs and other
      megakaryocyte progenitors. This results in an efficient replenishment of
      platelets that are lost during inflammatory insult. Thus, our study reveals an
      emergency machinery that counteracts life-threatening platelet depletions during
      acute inflammation.

PMID- 26299574
TI  - Resin-acid derivatives as potent electrostatic openers of voltage-gated K
      channels and suppressors of neuronal excitability.
AB  - Voltage-gated ion channels generate cellular excitability, cause diseases when
      mutated, and act as drug targets in hyperexcitability diseases, such as epilepsy,
      cardiac arrhythmia and pain. Unfortunately, many patients do not satisfactorily
      respond to the present-day drugs. We found that the naturally occurring resin
      acid dehydroabietic acid (DHAA) is a potent opener of a voltage-gated K channel
      and thereby a potential suppressor of cellular excitability. DHAA acts via a non
      traditional mechanism, by electrostatically activating the voltage-sensor domain,
      rather than directly targeting the ion-conducting pore domain. By systematic
      iterative modifications of DHAA we synthesized 71 derivatives and found 32
      compounds more potent than DHAA. The most potent compound, Compound 77, is 240
      times more efficient than DHAA in opening a K channel. This and other potent
      compounds reduced excitability in dorsal root ganglion neurons, suggesting that
      resin-acid derivatives can become the first members of a new family of drugs with
      the potential for treatment of hyperexcitability diseases. 

PMID- 26299575
TI  - Biomarkers of oxidative damage and antioxidant defense capacity in Caiman
      latirostris blood.
AB  - Several xenobiotics, and among them pesticides, can produce oxidative stress,
      providing a mechanistic basis for their observed toxicity. Chronic oxidative
      stress induces deleterious modifications to DNA, lipids and proteins that are
      used as effective biomarkers to study pollutant-mediated oxidative stress. No
      previous report existed on the application of oxidative damage and antioxidant
      defense biomarkers in Caiman latirostris blood, while few studies reported in
      other crocodilians were done in organs or muscles of dead animals. The aim of
      this study was to characterize a new set of oxidative stress biomarkers in C.
      latirostris blood, through the modification of conventional techniques: 1) damage
      to lipids by thiobarbituric acid reactive substances (TBARS), 2) damage to DNA by
      comet assay modified with the enzymes FPG and Endo III, and 3) antioxidant
      defenses: catalase, superoxide dismutase and glutathione; in order to apply them
      in future biomonitoring studies. We successfully adapted standard procedures for
      CAT, SOD, GSH and TBARS determination in C. latirostris blood. Calibration curves
      for FPG and Endo III showed that the three dilutions tested were appropriate to
      conduct the modified comet assay for the detection of oxidized bases in C.
      latirostris erythrocytes. One hour of incubation allowed a complete repair of the
      damage generated. The incorporation of these biomarkers in biomonitoring studies
      of caiman populations exposed to xenobiotics is highly important considering that
      this species has recovered from a serious endangered state through the
      implementation of sustainable use programs in Argentina, and represents nowadays
      a relevant economic resource for many human communities. 

PMID- 26299576
TI  - Kinetics, Mechanism, and Secondary Organic Aerosol Yield of Aqueous Phase Photo
      oxidation of alpha-Pinene Oxidation Products.
AB  - Formation of secondary organic aerosol (SOA) involves atmospheric oxidation of
      volatile organic compounds (VOCs), the majority of which are emitted from
      biogenic sources. Oxidation can occur not only in the gas-phase but also in
      atmospheric aqueous phases such as cloudwater and aerosol liquid water. This
      study explores for the first time the aqueous-phase OH oxidation chemistry of
      oxidation products of alpha-pinene, a major biogenic VOC species emitted to the
      atmosphere. The kinetics, reaction mechanisms, and formation of SOA compounds in
      the aqueous phase of two model compounds, cis-pinonic acid (PIN) and
      tricarballylic acid (TCA), were investigated in the laboratory; TCA was used as a
      surrogate for 3-methyl-1,2,3-butanetricarboxylic acid (MBTCA), a known alpha
      pinene oxidation product. Aerosol time-of-flight chemical ionization mass
      spectrometry (Aerosol-ToF-CIMS) was used to follow the kinetics and reaction
      mechanisms at the molecular level. Room-temperature second-order rate constants
      of PIN and TCA were determined to be 3.3 (+/- 0.5) * 10(9) and 3.1 (+/- 0.2) *
      10(8) M(-1) s(-1), respectively, from which were estimated their condensed-phase
      atmospheric lifetimes. Aerosol-ToF-CIMS detected a large number of products
      leading to detailed reaction mechanisms for PIN and MBTCA. By monitoring the
      particle size distribution after drying, the amount of SOA material remaining in
      the particle phase was determined. An aqueous SOA yield of 40 to 60% was
      determined for PIN OH oxidation. Although recent laboratory studies have focused
      primarily on aqueous-phase processing of isoprene-related compounds, we
      demonstrate that aqueous formation of SOA materials also occurs from monoterpene
      oxidation products, thus representing an additional source of biogenically driven
      aerosol formation.

PMID- 26299577
TI  - Household food insufficiency is associated with dietary intake in Korean adults.
AB  - OBJECTIVE: To examine the association of food insufficiency with dietary intake
      and eating and health behaviours. DESIGN: A cross-sectional study. SETTING: Data
      were obtained from a secondary source, the Fifth Korea National Health and
      Nutrition Examination Survey (2010-2012). SUBJECTS: The sample size consisted of
      15 603 adults over 19 years of age (8898 households). RESULTS: Significant
      differences in socio-economic factors were observed according to food
      insufficiency level (P<0.05), but BMI was similar among groups. Regarding
      macronutrients, lower protein intake and higher carbohydrate intake were found in
      the severely food-insufficient group, but we found no association with fat
      intake. Regarding micronutrients, Ca, Fe, vitamin A, thiamin, riboflavin niacin
      and vitamin C intakes were negatively associated with food insufficiency level (P
      trend<0.05). Consumption of different food groups, such as meat, fish, eggs and
      beans, vegetables and fruits, was significantly lower as food insufficiency level
      decreased after controlling for all possible variables; food group consumption
      also differed by sex. Overall eating and health behaviours were poorer in the
      mildly and severely food-insufficient groups, who received more food assistance
      but less nutritional education. CONCLUSIONS: Our results showed that dietary
      intake as well as eating and health behaviours are adversely associated with food
      insufficiency. These findings suggest that specific strategies to help food
      insufficient individuals should be developed in order to improve their dietary
      quality and health status.

PMID- 26299578
TI  - The use of an essay examination in evaluating medical students during the
      surgical clerkship.
AB  - BACKGROUND: Third-year medical students are graded according to subjective
      performance evaluations and standardized tests written by the National Board of
      Medical Examiners (NBME). Many "poor" standardized test takers believe the
      heavily weighted NBME does not evaluate their true fund of knowledge and would
      prefer a more open-ended forum to display their individualized learning
      experiences. Our study examined the use of an essay examination as part of the
      surgical clerkship evaluation. METHODS: We retrospectively examined the final
      surgical clerkship grades of 781 consecutive medical students enrolled in a large
      urban academic medical center from 2005 to 2011. We examined final grades with
      and without the inclusion of the essay examination for all students using a
      paired t test and then sought any relationship between the essay and NBME using
      Pearson correlations. RESULTS: Final average with and without the essay
      examination was 72.2% vs 71.3% (P < .001), with the essay examination increasing
      average scores by .4, 1.8, and 2.5 for those receiving high pass, pass, and fail,
      respectively. The essay decreased the average score for those earning an honors
      by .4. Essay scores were found to overall positively correlate with the NBME (r =
      .32, P < .001). CONCLUSIONS: The inclusion of an essay examination as part of the
      third-year surgical core clerkship final did increase the final grade a modest
      degree, especially for those with lower scores who may identify themselves as
      "poor" standardized test takers. A more open-ended forum may allow these students
      an opportunity to overcome this deficiency and reveal their true fund of surgical
      knowledge.

PMID- 26299581
TI  - Olive leaf components apigenin 7-glucoside and luteolin 7-glucoside direct human
      hematopoietic stem cell differentiation towards erythroid lineage.
AB  - The generation of blood cellular components from hematopoietic stem cells is
      important for the therapy of a broad spectrum of hematological disorders. In
      recent years, several lines of evidence suggested that certain nutrients,
      vitamins and flavonoids may have important roles in controlling the stem cell
      fate decision by maintaining their self-renewal or stimulating the lineage
      specific differentiation. In this study, main olive leaf phytochemicals
      oleuropein (Olp), apigenin 7-glucoside (Api7G) and luteolin 7-glucoside (Lut7G)
      were investigated for their potential effects on hematopoietic stem cell
      differentiation using both phenotypic and molecular analysis. Oleuropein and the
      combination of the three compounds enhanced the differentiation of CD34+ cells
      into myelomonocytic cells and lymphocytes progenitors and inhibited the
      commitment to megakaryocytic and erythroid lineages. Treatment with Lut7G
      stimulated both the erythroid and the myeloid differentiation, while treatment
      with Api7G specifically induced the differentiation of CD34+ cells towards the
      erythroid lineage and inhibited the myeloid differentiation. Erythroid
      differentiation induced by Api7G and Lut7G treatments was confirmed by the
      increase in hemoglobin genes expressions (alpha-hemoglobin, beta-hemoglobin and
      gamma-hemoglobin) and erythroid transcription factor GATA1 expression. As
      revealed by microarray analysis, the mechanisms underlying the erythroid
      differentiation-inducing effect of Api7G on hematopoietic stem cells involves the
      activation of JAK/STAT signaling pathway. These findings prove the
      differentiation-inducing effects of olive leaf compounds on hematopoietic stem
      cells and highlight their potential use in the ex vivo generation of blood cells.

PMID- 26299579
TI  - MiR-126 Contributes to Human Umbilical Cord Blood Cell-Induced Neurorestorative
      Effects After Stroke in Type-2 Diabetic Mice.
AB  - Diabetes mellitus (DM) is a high risk factor for stroke and leads to more severe
      vascular and white-matter injury than stroke in non-DM. We tested the
      neurorestorative effects of delayed human umbilical cord blood cell (HUCBC)
      treatment of stroke in type-2 diabetes (T2DM). db/db-T2DM and db/+-non-DM mice
      were subjected to distal middle cerebral artery occlusion (dMCAo) and were
      treated 3 days after dMCAo with: (a) non-DM + Phosphate buffered saline (PBS);
      (b) T2DM + PBS; (c) T2DM + naive-HUCBC; (d) T2DM + miR-126(-/-) HUCBC. Functional
      evaluation, vascular and white-matter changes, neuroinflammation, and miR-126
      effects were measured in vivo and in vitro. T2DM mice exhibited significantly
      decreased serum and brain tissue miR-126 expression compared with non-DM mice.
      T2DM + HUCBC mice exhibited increased miR-126 expression, increased tight
      junction protein expression, axon/myelin, vascular density, and M2-macrophage
      polarization. However, decreased blood-brain barrier leakage, brain hemorrhage,
      and miR-126 targeted gene vascular cell adhesion molecule-1 and monocyte
      chemotactic protein 1 expression in the ischemic brain as well as improved
      functional outcome were present in HUCBC-treated T2DM mice compared with control
      T2DM mice. MiR-126(-/-) HUCBC-treatment abolished the benefits of naive-HUCBC
      treatment in T2DM stroke mice. In vitro, knock-in of miR-126 in primary cultured
      brain endothelial cells (BECs) or treatment of BECs with naive-HUCBCs
      significantly increased capillary-like tube formation, and increased axonal
      outgrowth in primary cultured cortical neurons; whereas treatment of BECs or
      cortical neurons with miR-126(-/-) HUCBC attenuated HUCBC-treatment-induced
      capillary tube formation and axonal outgrowth. Our data suggest delayed HUCBC
      treatment of stroke increases vascular/white-matter remodeling and anti
      inflammatory effects; MiR-126 may contribute to HUCBC-induced neurorestorative
      effects in T2DM mice.

PMID- 26299580
TI  - Curcumin as therapeutics for the treatment of head and neck squamous cell
      carcinoma by activating SIRT1.
AB  - SIRT1 is one of seven mammalian homologs of Sir2 that catalyzes NAD(+)-dependent
      protein deacetylation. The aim of the present study is to explore the effect of
      SIRT1 small molecule activator on the anticancer activity and the underlying
      mechanism. We examined the anticancer activity of a novel oral agent, curcumin,
      which is the principal active ingredient of the traditional Chinese herb Curcuma
      Longa. Treatment of FaDu and Cal27 cells with curcumin inhibited growth and
      induced apoptosis. Mechanistic studies showed that anticancer activity of
      curcumin is associated with decrease in migration of HNSCC and associated
      angiogenesis through activating of intrinsic apoptotic pathway (caspase-9) and
      extrinsic apoptotic pathway (caspase-8). Our data demonstrating that anticancer
      activity of curcumin is linked to the activation of the ATM/CHK2 pathway and the
      inhibition of nuclear factor-kappaB. Finally, increasing SIRT1 through small
      molecule activator curcumin has shown beneficial effects in xenograft mouse
      model, indicating that SIRT1 may represent an attractive therapeutic target. Our
      studies provide the preclinical rationale for novel therapeutics targeting SIRT1
      in HNSCC. 

PMID- 26299582
TI  - Evaluation of the new AmpliSens multiplex real-time PCR assay for simultaneous
      detection of Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium,
      and Trichomonas vaginalis.
AB  - In this study, we performed an evaluation of the new CE-marked multiplex real
      time AmpliSens N.gonorrhoeae/C.trachomatis/M.genitalium/T.vaginalis-MULTIPRIME
      FRT PCR assay compared to APTIMA tests, i.e., APTIMA COMBO 2 assay, APTIMA
      Trichomonas vaginalis assay (FDA-approved), and two different APTIMA Mycoplasma
      genitalium assays (research use only; one of them only used for discrepancy
      analysis). Vaginal swabs (n = 209) and first-void urine (FVU) specimens from
      females (n = 498) and males (n = 554), consecutive attendees (n = 1261) at a
      dermatovenerological clinic in Sweden, were examined. The sensitivity of the
      AmpliSens PCR assay for detection of C. trachomatis (6.3% prevalence), M.
      genitalium (5.7% prevalence), N. gonorrhoeae (0.3% prevalence), and T. vaginalis
      (0.08% prevalence) was 97.5% (95% confidence interval (CI): 91.2-99.6%), 81.9%
      (95% CI: 70.7-89.7%), 100% (95% CI: 40.2-100%) and 100% (95% CI: 16.5-100%),
      respectively. The specificity of the AmpliSens PCR assay was 100% (95% CI: 99.6
      100%) for all agents. The analytical sensitivity and specificity for N.
      gonorrhoeae detection was excellent, i.e., 55 international gonococcal strains
      detected and 135 isolates of 13 non-gonococcal Neisseria species were negative.
      In conclusion, the multiplex real-time AmpliSens
      N.gonorrhoeae/C.trachomatis/M.genitalium/T.vaginalis-MULTIPRIME-FRT PCR assay
      demonstrated high sensitivity and excellent specificity for the detection of C.
      trachomatis, N. gonorrhoeae, and T. vaginalis, and excellent specificity but
      suboptimal sensitivity for M. genitalium detection. 

PMID- 26299583
TI  - Encephalitozoon hellem in a patient with CD4+ T-cell prolymphocytic leukemia:
      case report and genomic identification.
AB  - Five cases of microsporidioses among leukemic patients, 4 in myeloid-leukemic
      patients and 1 in a chronic lymphocytic leukemia, have been described until now.
      We report a case of microsporidiosis and the genomic identification of
      Encephalitozoon hellem in a patient with CD4(+) T-cell prolymphocytic leukemia. 

PMID- 26299584
TI  - Reproductive character displacement of female mate preferences for male cuticular
      hydrocarbons in Drosophila subquinaria.
AB  - Several lines of evidence implicate sexual isolation in both initiating and
      completing the speciation process. Although its existence is straightforward to
      demonstrate, understanding the evolution of sexual isolation requires identifying
      the underlying phenotypes responsible so that we can determine how these have
      diverged. Here, we study geographic variation in female mate preferences for male
      sexual displays in the fly Drosophila subquinaria. Female D. subquinaria that are
      sympatric with its sister species D. recens discriminate strongly against both D.
      recens and allopatric conspecific males, whereas females from allopatric
      populations do not. Furthermore, female mate preferences target at least in part
      a suite of cuticular hydrocarbons (CHCs) in males and geographic variation in
      CHCs mirrors the pattern of mate discrimination. In this study, we quantify
      female mate preferences for male CHCs from populations that span the geographic
      range of D. subquinaria. We find that the direction of linear sexual selection
      varies significantly between populations that are sympatric versus allopatric
      with D. recens in a pattern of reproductive character displacement. Differences
      in preference partially align with existing differences in CHCs and patterns of
      sexual isolation, although discrepancies remain that suggest the involvement of
      additional traits and/or more complex, nonlinear preference functions.

PMID- 26299585
TI  - Toxic erythema with eccrine squamous syringometaplasia induced by nanoparticle
      albumin-bound paclitaxel.

PMID- 26299586
TI  - Lactation and appetite-regulating hormones: increased maternal plasma peptide YY
      concentrations 3-6 months postpartum.
AB  - Breast-feeding is associated with maternal hormonal and metabolic changes
      ensuring adequate milk production. In this study, we investigate the impact of
      breast-feeding on the profile of changes in maternal appetite-regulating hormones
      3-6 months postpartum. Study participants were age- and BMI-matched lactating
      mothers (n 10), non-lactating mothers (n 9) and women without any history of
      pregnancy or breast-feeding in the previous 12 months (control group, n 10).
      During study sessions, young mothers breast-fed or bottle-fed their babies, and
      maternal blood samples were collected at five time points during 90 min: before,
      during and after feeding the babies. Outcome parameters were plasma
      concentrations of ghrelin, peptide YY (PYY), leptin, adiponectin, prolactin,
      cortisol, insulin, glucose and lipid values. At baseline, circulating PYY
      concentrations were significantly increased in lactating mothers (100.3 (se 6.7)
      pg/ml) v. non-lactating mothers (73.6 (se 4.9) pg/ml, P=0.008) and v. the control
      group (70.2 (se 9) pg/ml, P=0.021). We found no differences in ghrelin, leptin
      and adiponectin values. Baseline prolactin concentrations were over 4-fold higher
      in lactating mothers (P<0.001). Lactating women had reduced TAG levels and LDL
      cholesterol:HDL-cholesterol ratio, but increased waist circumference, when
      compared with non-lactating women. Breast-feeding sessions further elevated
      circulating prolactin (P<0.001), but induced no acute effects on appetite
      regulating hormones. In summary, one single breast-feeding session did not
      acutely modulate circulating appetite-regulating hormones, but increased baseline
      PYY concentrations are associated with prolonged lactation. PYY might play a role
      in the coordination of energy balance during lactation, increasing fat
      mobilisation from maternal depots and ensuring adequate milk production for the
      demands of the growing infant. 

PMID- 26299587
TI  - Autophagy: Surviving stress in pancreatic cancer.

PMID- 26299594
TI  - The efficacy of music therapy for people with dementia: A meta-analysis of
      randomised controlled trials.
AB  - AIMS AND OBJECTIVES: To (1) perform a meta-analysis of randomised controlled
      trials pertaining to the efficacy of music therapy on disruptive behaviours,
      anxiety levels, depressive moods and cognitive functioning in people with
      dementia; and (2) clarify which interventions, therapists and participant
      characteristics exerted higher and more prominent effects. BACKGROUND: Present
      study was the first to perform a meta-analysis that included all the randomised
      controlled trials found in literature relating to music therapy for people with
      dementia over the past 15 years. DESIGN: A meta-analysis study design. METHODS:
      Quantitative studies were retrieved from PubMed, Medline, Cochrane Library
      Database, CINAHL, SCOPUS and PsycINFO. A meta-analysis was used to calculate the
      overall effect sizes of music therapy on outcome indicators. RESULTS: Music
      therapy significantly improved disruptive behaviours [Hedges' g = -0.66; 95%
      confidence interval (CI) = -0.44 to -0.88] and anxiety levels (Hedges' g = -0.51;
      95% CI = -0.02 to -1.00) in people with dementia. Music therapy might affect
      depressive moods (Hedges' g = -0.39; 95% CI = 0.01 to -0.78), and cognitive
      functioning (Hedges' g = 0.19; 95% CI = 0.45 to -0.08). CONCLUSION: Music therapy
      exerted a moderately large effect on disruptive behaviours of people with
      dementia, a moderate effect on anxiety levels and depressive moods, and a small
      effect on cognitive functioning. RELEVANCE TO CLINICAL PRACTICE: Individual music
      therapy provided once a week to patients with cognitive functioning and manual
      guided in music intervention construction is suggested. Group music therapy is
      provided several times a week to reduce their disruptive behaviours, anxiety
      levels and depressive moods. Music therapy is a cost-effective, enjoyable,
      noninvasive therapy and could be useful for clinical nurses in creating an
      environment that is conducive to the well-being of patients with dementia.

PMID- 26299592
TI  - Deoxyribonucleotide metabolism, mutagenesis and cancer.
AB  - Cancer was recognized as a genetic disease at least four decades ago, with the
      realization that the spontaneous mutation rate must increase early in
      tumorigenesis to account for the many mutations in tumour cells compared with
      their progenitor pre-malignant cells. Abnormalities in the deoxyribonucleotide
      pool have long been recognized as determinants of DNA replication fidelity, and
      hence may contribute to mutagenic processes that are involved in carcinogenesis.
      In addition, many anticancer agents antagonize deoxyribonucleotide metabolism.
      Here, we consider the extent to which aspects of deoxyribonucleotide metabolism
      contribute to our understanding of both carcinogenesis and to the effective use
      of anticancer agents. 

PMID- 26299596
TI  - The Development and Validation of the Social Networking Experiences
      Questionnaire: A Measure of Adolescent Cyberbullying and Its Impact.
AB  - The measurement of cyberbullying has been marked by several inconsistencies that
      lead to difficulties in cross-study comparisons of the frequency of occurrence
      and the impact of cyberbullying. Consequently, the first aim of this study was to
      develop a measure of experience with and impact of cyberbullying victimization in
      social networking sites in adolescents. The second aim was to investigate the
      psychometric properties of a purpose-built measure (Social Networking Experiences
      Questionnaire [SNEQ]). Exploratory factor analysis on 253 adolescent social
      networking sites users produced a six-factor model of impact. However, one factor
      was removed because of low internal consistency. Cronbach's alpha was higher than
      .76 for the victimization and remaining five impact subscales. Furthermore,
      correlation coefficients for the Victimization scale and related dimensions
      showed good construct validity. The utility of the SNEQ for victim support
      personnel, research, and cyberbullying education/prevention programs is
      discussed. 

PMID- 26299595
TI  - Mouse model of endoscopically ablated enteric nervous system.
AB  - BACKGROUND: Current transgenic animal models of Hirschsprung disease are
      restricted by limited survival and need for special dietary care. We used small
      animal colonoscopy to produce chemically ablated enteric nervous system in the
      distal colon and rectum of normal mice. MATERIALS AND METHODS: Adult C57BL/6 mice
      underwent colonoscopy with submucosal injection of 75-100 MUL of saline (n = 2)
      or 0.002% (n = 2), 0.02% (n = 15), or 0.2% (n = 2) benzalkonium chloride (BAC).
      Each mouse received 1-3 injections in the distal colon and rectum. Mice were
      sacrificed on postprocedure day 7 or 28. Injection sites were analyzed
      histologically and with immunostaining for beta-tubulin III. RESULTS: Submucosal
      injection of 0.02% BAC resulted in megacolon and obliteration of 82 +/- 8.8% of
      myenteric ganglia at the injection site on postprocedure day 7 compared with
      normal colon. This effect was sustained until day 28. Injection of 0.002% BAC had
      little effect on the myenteric neuronal network at these time points. Multiple
      injections of 0.002% or 0.02% BAC (up to three injections per mouse) were well
      tolerated. Injection of 0.2% BAC caused acute toxicity or death. CONCLUSIONS: A
      novel model of chemically ablated enteric nervous system in the mouse colon and
      rectum is introduced. This model can be valuable in evaluating targeted cell
      delivery therapies for Hirschsprung disease.

PMID- 26299593
TI  - Sympathetic nervous system regulation of the tumour microenvironment.
AB  - The peripheral autonomic nervous system (ANS) is known to regulate gene
      expression in primary tumours and their surrounding microenvironment. Activation
      of the sympathetic division of the ANS in particular modulates gene expression
      programmes that promote metastasis of solid tumours by stimulating macrophage
      infiltration, inflammation, angiogenesis, epithelial-mesenchymal transition and
      tumour invasion, and by inhibiting cellular immune responses and programmed cell
      death. Haematological cancers are modulated by sympathetic nervous system (SNS)
      regulation of stem cell biology and haematopoietic differentiation programmes. In
      addition to identifying a molecular basis for physiologic stress effects on
      cancer, these findings have also identified new pharmacological strategies to
      inhibit cancer progression in vivo. 

PMID- 26299597
TI  - Factors Affecting Hurricane Evacuation Intentions.
AB  - Protective actions for hurricane threats are a function of the environmental and
      information context; individual and household characteristics, including cultural
      worldviews, past hurricane experiences, and risk perceptions; and motivations and
      barriers to actions. Using survey data from the Miami-Dade and Houston-Galveston
      areas, we regress individuals' stated evacuation intentions on these factors in
      two information conditions: (1) seeing a forecast that a hurricane will hit one's
      area, and (2) receiving an evacuation order. In both information conditions
      having an evacuation plan, wanting to keep one's family safe, and viewing one's
      home as vulnerable to wind damage predict increased evacuation intentions. Some
      predictors of evacuation intentions differ between locations; for example,
      Florida respondents with more egalitarian worldviews are more likely to evacuate
      under both information conditions, and Florida respondents with more
      individualist worldviews are less likely to evacuate under an evacuation order,
      but worldview was not significantly associated with evacuation intention for
      Texas respondents. Differences by information condition also emerge, including:
      (1) evacuation intentions decrease with age in the evacuation order condition but
      increase with age in the saw forecast condition, and (2) evacuation intention in
      the evacuation order condition increases among those who rely on public sources
      of information on hurricane threats, whereas in the saw forecast condition
      evacuation intention increases among those who rely on personal sources. Results
      reinforce the value of focusing hurricane information efforts on evacuation plans
      and residential vulnerability and suggest avenues for future research on how
      hurricane contexts shape decision making. 

PMID- 26299598
TI  - Editorial.

PMID- 26299599
TI  - Supplement for the 2015 Annual Scientific Meeting of the British Society of
      Paediatric Dentistry, Bath, UK, 3-4 September.

PMID- 26299600
TI  - Unloading the hired gun: Inoculation effects in expert witness testimony.
AB  - The current study investigated the efficacy of inoculation as a trial strategy
      designed to counter mock jurors' perceptions that an expert is a hired gun in a
      criminal trial. The effect of narrative and fragmented expert responses to cross
      examination questions was also examined. The significant results were that not
      using inoculation led to higher ratings of expert knowledge compared to other
      conditions. Response style did not make a difference in the criminal setting.
      Implications of these results regarding "hired gun" expert witnesses and
      courtroom persuasion are discussed. 

PMID- 26299601
TI  - Psychosocial adversity, delinquent pathway and internalizing psychopathology in
      juvenile male offenders.
AB  - The main aim of the present study was to investigate the presence of a set of
      risk factors relating to childhood life events and other psychosocial factors
      that may be associated with criminal indicators and with the prevalence of
      internalizing psychopathology in a sample of adolescent offenders. Fifty male
      adolescents in the custody of the Portuguese Juvenile Justice System participated
      in the study (M=15.8 years of age). The Adolescent Psychopathology Scale - Short
      Form (APS-SF) was administered in a structured interview format, and the
      sociodemographic, family and criminal data questionnaire was filled in by the
      justice professional after consulting the adolescent's file. Forty-six percent of
      all subjects had previous delinquent behavior. About 32% of the boys had
      committed violent offenses and 88% acted with peers. Also, the persistence of the
      delinquent behavior (50% of the offenders), coupled with the increase in the
      severity of the crimes committed (38% of the sample), suggests that these
      adolescents were at risk for serious and chronic delinquency at the time of the
      intervention. About 32% of the participants reported posttraumatic stress
      disorder symptoms, 20% had suicide ideation, and a lower percentage reported
      other internalizing problems. Institutionalization, maltreatment and conduct
      problems in childhood, and family risk factors (parental conflict, absence of a
      father figure, lack of parental control and family substance addiction) were
      related with the report of internalizing problems. Moreover, the increase in the
      severity of criminal offenses and living in a correctional facility were
      associated with higher levels of posttraumatic stress, interpersonal problems,
      anxiety and depression. This study draws attention to the importance of assessing
      indicators of psychopathology and of psychosocial risk in intervention programs
      with young offenders, but also to the need of family focused interventions in
      order to help prevent recidivism.

PMID- 26299603
TI  - Trends in euthanasia and assisted suicide.

PMID- 26299602
TI  - Expression of plectasin in Bacillus subtilis using SUMO technology by a maltose
      inducible vector.
AB  - Plectasin, the first fungus defensin, is especially efficient against Gram
      positive bacteria. To explore an effective approach for expressing plectasin in
      Bacillus subtilis, the sequence encoding plectasin fused with the small ubiquitin
      like modifier (SUMO) gene, the 6 * His gene and the signal peptide of SacB were
      cloned into an E. coli-B. subtilis shuttle vector pGJ148 in which the maltose
      utilization operon promoter Pglv directed the expression. The fusion protein
      successfully secreted in culture and approximately, 41 mg of the recombinant
      fusion protein SUMO-plectasin was purified per liter of culture supernatant.
      After purification by Ni-NTA resin column and digestion by SUMO protease, 5.5 mg
      of plectasin with a purity of 94 % was obtained from 1 L fermentation culture.
      Recombinant plectasin was found inhibition activity against S. pneumoniae, S.
      aureus and S. epidermidis. These results indicate that the maltose-induced
      expression system may be a safe and efficient way for the large-scale production
      of soluble peptides in B. subtilis.

PMID- 26299604
TI  - High HLA-DP expression and graft-versus-host disease.

PMID- 26299605
TI  - Genetic mutations and outcome in myeloma.

PMID- 26299606
TI  - Azathioprine-induced Sweet's syndrome: A case series and review of the
      literature.
AB  - We present three patients with azathioprine-induced Sweet's syndrome (AISS) who
      attended our tertiary institution within a 12-month period. Established
      associations exist between Sweet's syndrome and some medications; however, to
      date links to azathioprine are tentative. While there are case reports of AISS,
      most have occurred in patients with inflammatory bowel disease (IBD), an
      underlying predisposition for Sweet's syndrome. Our case series adds to the
      evidence that the entity of AISS truly exists independent of confounding factors
      such as concurrent IBD.

PMID- 26299607
TI  - Efficacy of acupuncture in the management of atopic dermatitis: a systematic
      review.
AB  - Atopic dermatitis (AD) has a high negative impact on quality of life. Acupuncture
      has antipruritic actions and may assist in treatment of AD; however, the current
      state of evidence for this remains unknown. We aimed to evaluate the efficacy of
      acupuncture against placebo/sham acupuncture in the management of AD. Electronic
      searches were conducted on a number of databases, from their inception until
      November 2013. Studies comparing the effects of acupuncture with those of
      placebo/sham acupuncture on severity of disease or symptoms/signs of AD were
      included. We did not find any studies that were eligible to be included in this
      systematic review. Among the excluded studies, there were two studies that
      evaluated the antipruritic effects of acupuncture and one study that evaluated
      the effects of acupuncture on IgE-mediated allergy. However, there were no
      randomized controlled trials evaluating the effects of acupuncture on AD as a
      disease. This finding therefore provides an indication of the current state of
      evidence of acupuncture in the management of AD, and highlights the research gap
      that exists, in that there is a lack of gold-standard studies (i.e. RCTs) to
      support valid conclusions. There is currently no evidence of the effects of
      acupuncture in the management of AD, and no evidence-based recommendations or
      conclusions can be made from this review. Several studies indicated that
      acupuncture may have a role in reducing itch or regulating IgE-mediated allergy,
      both of which are major characteristics of AD. However, there were no RCTs
      evaluating the effects of acupuncture on AD as a disease. There is therefore an
      urgent need for rigorously designed RCTs to assess the efficacy of acupuncture in
      the management of AD. 

PMID- 26299608
TI  - Therapy escape mechanisms in the malignant prostate.
AB  - Androgen receptor (AR) is the main target for prostate cancer therapy. Clinical
      approaches for AR inactivation include chemical castration, inhibition of
      androgen synthesis and AR antagonists (anti-androgens). However, treatment
      resistance occurs for which an important number of therapy escape mechanisms have
      been identified. Herein, we summarise the current knowledge of molecular
      mechanisms underlying therapy resistance in prostate cancer. Moreover, the tumour
      escape mechanisms are arranged into the concepts of target modification, bypass
      signalling, histologic transformation, cancer stem cells and miscellaneous
      mechanisms. This may help researchers to compare and understand same or similar
      concepts of therapy resistance in prostate cancer and other cancer types. 

PMID- 26299609
TI  - Improved Fuzzy C-Means based Particle Swarm Optimization (PSO) initialization and
      outlier rejection with level set methods for MR brain image segmentation.
AB  - In this paper, a new image segmentation method based on Particle Swarm
      Optimization (PSO) and outlier rejection combined with level set is proposed. A
      traditional approach to the segmentation of Magnetic Resonance (MR) images is the
      Fuzzy C-Means (FCM) clustering algorithm. The membership function of this
      conventional algorithm is sensitive to the outlier and does not integrate the
      spatial information in the image. The algorithm is very sensitive to noise and in
      homogeneities in the image, moreover, it depends on cluster centers
      initialization. To improve the outlier rejection and to reduce the noise
      sensitivity of conventional FCM clustering algorithm, a novel extended FCM
      algorithm for image segmentation is presented. In general, in the FCM algorithm
      the initial cluster centers are chosen randomly, with the help of PSO algorithm
      the clusters centers are chosen optimally. Our algorithm takes also into
      consideration the spatial neighborhood information. These a priori are used in
      the cost function to be optimized. For MR images, the resulting fuzzy clustering
      is used to set the initial level set contour. The results confirm the
      effectiveness of the proposed algorithm. 

PMID- 26299610
TI  - Impact of residual platelet reactivity under clopidogrel treatment for lesions
      and the clinical outcome after drug-eluting stent implantation in patients with
      hemodialysis.
AB  - BACKGROUND: Hemodialysis (HD) patients are at high risk for adverse clinical
      outcomes after drug-eluting stent (DES) implantation. However, the impact of
      residual platelet reactivity under dual anti-platelet therapy in this subset of
      patients remains unclear. METHODS: We enrolled 142 stable angina patients (194
      lesions) treated with DES, who were taking aspirin and 75mg clopidogrel and had
      undergone 8-month angiography with optical coherence tomography (OCT). OCT
      findings and major adverse cardiac events (MACEs) at 1 year (cardiac death, acute
      coronary syndrome, target lesion and vessel revascularization, and stent
      thrombosis) were compared between 28 HD patients and 114 non-HD patients.
      Responsiveness to clopidogrel was assessed by measuring P2Y12 reaction unit (PRU)
      at 8 months. RESULTS: PRU was significantly higher in HD patients than in non-HD
      patients (p=0.006), even though proportion of cytochrome P450 2C19 genotype was
      equivalent. HD patients had a significantly higher rate of thrombi formation
      (assessed using OCT) and MACEs than non-HD patients (thrombi: p=0.001; MACEs:
      p=0.0001). The PRU value was independently associated with MACEs in both groups.
      The optimal cutoff values of PRU for predicting MACEs were 235 for HD patients
      and 259 for non-HD patients. CONCLUSIONS: HD was associated with a high residual
      platelet reactivity, which may contribute to the higher incidence of MACEs after
      DES implantation in HD patients. HD may be a patient profile that merits a more
      potent anti-platelet regimen.

PMID- 26299611
TI  - Pulmonary hypertension due to left heart disease: The prognostic implications of
      diastolic pulmonary vascular pressure gradient.
AB  - BACKGROUND: Compared to transpulmonary pressure gradient (TPPG), diastolic
      pulmonary vascular pressure gradient (DPG) may be a more sensitive and specific
      indicator for pulmonary hypertension (PH) due to left heart disease (LHD) with
      significant pulmonary vascular disease (PVD). The aim of this study was to
      investigate the incidence and clinical features of PH-LHD with PVD classified by
      DPG and TPPG. METHODS: We analyzed 410 patients admitted for symptomatic heart
      failure (HF) (New York Heart Association >=2) and who underwent right heart
      catheterization (RHC) at compensated stage between 2007 and 2012. Patients with
      PH-LHD were divided into 3 groups according to the value of DPG and TPPG (Non-PVD
      group: DPG <7mmHg and TPPG <=12mmHg; TPPG-PVD group: DPG <7mmHg and TPPG >12mmHg;
      DPG-PVD group: DPG >=7mmHg). Multivariate Cox regression analysis was applied to
      investigate whether each PH-LHD category predicts death or HF readmission after
      adjusting for other variables. RESULTS: PH-LHD was observed in 164 patients (40%)
      with symptomatic HF. Thirteen patients (3%) were allocated into DPG-PVD group,
      while 24 patients were allocated into TPPG-PVD group (6%). DPG-PVD group was
      significantly associated with death or HF readmission compared to non-PVD group
      (hazard ratio: 3.57; 95% CI: 1.33 to 9.55, p=0.01), while the association between
      TPPG-PVD group and non-PVD group did not reach statistical significance (hazard
      ratio: 1.89; 95% CI: 0.77 to 4.64, p=0.17). CONCLUSIONS: PH-LHD with PVD
      classified by DPG was significantly associated with poor long-term clinical
      outcomes, whereas the association between PH-LHD with PVD classified by TPPG and
      clinical outcomes did not reach statistical significance. However, further
      studies are needed, because there was no substantial difference in clinical
      outcomes between PH-LHD with PVD classified by DPG and PH-LHD with PVD classified
      by TPPG.

PMID- 26299612
TI  - The metastatic infiltration at the metastasis/brain parenchyma-interface is very
      heterogeneous and has a significant impact on survival in a prospective study.
AB  - The current approach to brain metastases resection is macroscopic removal of
      metastasis until reaching the glial pseudo-capsule (gross total resection (GTR)).
      However, autopsy studies demonstrated infiltrating metastatic cells into the
      parenchyma at the metastasis/brain parenchyma (M/BP)-interface. AIMS/METHODS: To
      analyze the astrocyte reaction and metastatic infiltration pattern at the M/BP
      interface with an organotypic brain slice coculture system. Secondly, to evaluate
      the significance of infiltrating metastatic tumor cells in a prospective biopsy
      study. Therefore, after GTR, biopsies were obtained from the brain parenchyma
      beyond the glial pseudo-capsule and analyzed histomorphologically. RESULTS: The
      coculture revealed three types of cancer cell infiltration. Interestingly, the
      astrocyte reaction was significantly different in the coculture with a benign,
      neuroectodermal-derived cell line. In the prospective biopsy study 58/167 (34.7%)
      samples revealed infiltrating metastatic cells. Altogether, 25/39 patients
      (64.1%) had proven to exhibit infiltration in at least one biopsy specimen with
      significant impact on survival (OS) (3.4 HR; p = 0.009; 2-year OS was 6.6% versus
      43.5%). Exceptionally, in the non-infiltrating cohort three patients were long
      term survivors. CONCLUSIONS: Metastatic infiltration has a significant impact on
      prognosis. Secondly, the astrocyte reaction at the M/BP-interface is
      heterogeneous and supports our previous concept of the organ-specific defense
      against metastatic (organ-foreign) cells.

PMID- 26299613
TI  - FOXM1 is a downstream target of LPA and YAP oncogenic signaling pathways in high
      grade serous ovarian cancer.
AB  - Lysophosphatidic acid (LPA), a prototypical ligand for G protein coupled
      receptors, and Forkhead box protein M1 (FOXM1), a transcription factor that
      regulates expression of a wide array of genes involved in cancer initiation and
      progression, are two important oncogenic signaling molecules in human epithelial
      ovarian cancers (EOC). We conducted in vitro mechanistic studies using
      pharmacological inhibitors, genetic forms of the signaling molecules, and RNAi
      mediated gene knock-down to uncover the molecular mechanisms of how these two
      molecules interact in EOC cells. Additionally, in vivo mouse studies were
      performed to confirm the functional involvement of FOXM1 in EOC tumor formation
      and progression. We show for the first time that LPA up-regulates expression of
      active FOXM1 splice variants in a time- and dose-dependent manner in the human
      EOC cell lines OVCA433, CAOV3, and OVCAR5. Gi-PI3K-AKT and G12/13-Rho-YAP
      signaling pathways were both involved in the LPA receptor (LPA1-3) mediated up
      regulation of FOXM1 at the transcriptional level. In addition, down-regulation of
      FOXM1 in CAOV3 xenografts significantly reduced tumor and ascites formation,
      metastasis, and expression of FOXM1 target genes involved in cell proliferation,
      migration, or invasion. Collectively, our data link the oncolipid LPA, the
      oncogene YAP, and the central regulator of cell proliferation/mutagenesis FOXM1
      in EOC cells. Moreover, these results provide further support for the importance
      of these pathways as potential therapeutic targets in EOC. 

PMID- 26299614
TI  - Spatiotemporal control of gene expression in bone-marrow derived cells of the
      tumor microenvironment induced by MRI guided focused ultrasound.
AB  - The tumor microenvironment is an interesting target for anticancer therapies but
      modifying this compartment is challenging. Here, we demonstrate the feasibility
      of a gene therapy strategy that combined targeting to bone marrow-derived tumor
      microenvironment using genetically modified bone-marrow derived cells and control
      of transgene expression by local hyperthermia through a thermo-inducible
      promoter. Chimera were obtained by engraftment of bone marrow from transgenic
      mice expressing reporter genes under transcriptional control of heat shock
      promoter and inoculated sub-cutaneously with tumors cells. Heat shocks were
      applied at the tumor site using a water bath or magnetic resonance guided high
      intensity focused ultrasound device. Reporter gene expression was followed by
      bioluminescence and fluorescence imaging and immunohistochemistry. Bone marrow
      derived cells expressing reporter genes were identified to be mainly tumor
      associated macrophages. We thus provide the proof of concept for a gene therapy
      strategy that allows for spatiotemporal control of transgenes expression by
      macrophages targeted to the tumor microenvironment. 

PMID- 26299615
TI  - New therapeutic strategies in neuroblastoma: combined targeting of a novel
      tyrosine kinase inhibitor and liposomal siRNAs against ALK.
AB  - Many different aberrations in the Anaplastic Lymphoma Kinase (ALK) were found to
      be oncogenic drivers in several cancers including neuroblastoma (NB), therefore
      ALK is now considered a critical player in NB oncogenesis and a promising
      therapeutic target. The ALK-inhibitor crizotinib has a limited activity against
      the various ALK mutations identified in NB patients. We tested: the activity of
      the novel ALK-inhibitor X-396 administered alone or in combination with Targeted
      Liposomes carrying ALK-siRNAs (TL[ALK-siRNA]) that are active irrespective of ALK
      gene mutational status; the pharmacokinetic profiles and the biodistribution of X
      396; the efficacy of X-396 versus crizotinib treatment in NB xenografts; whether
      the combination of X-396 with the TL[ALK-siRNA] could promote long-term survival
      in NB mouse models. X-396 revealed good bioavailability, moderate half-life, high
      mean plasma and tumor concentrations. X-396 was more effective than crizotinib in
      inhibiting in vitro cell proliferation of NB cells and in reducing tumor volume
      in subcutaneous NB models in a dose-dependent manner. In orthotopic NB
      xenografts, X-396 significantly increased life span independently of the ALK
      mutation status. In combination studies, all effects were significantly improved
      in the mice treated with TL[ALK-siRNA] and X-396 compared to mice receiving the
      single agents. Our findings provide a rational basis to design innovative
      molecular-based treatment combinations for clinical application in ALK-driven NB
      tumors.

PMID- 26299616
TI  - Evaluating blood levels of neuron specific enolase, chromogranin A, and
      circulating tumor cells as Merkel cell carcinoma biomarkers.
AB  - BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin
      cancer. Although used to monitor MCC patients, the clinical utility of neuron
      specific enolase (NSE) and chromogranin A (ChrA) blood levels is untested. EpCAM
      positive circulating tumor cells (CTC) reflect disease status in several
      epithelial tumors. Here we investigate the use of NSE and ChrA blood levels and
      CTC counts as biomarkers for MCC disease behavior. METHODS: NSE and ChrA blood
      levels from 60 patients with MCC were retrospectively analyzed; 30 patients were
      additionally screened for CTC. Biomarker values were correlated to clinical
      parameters. RESULTS: Despite routine use by some physicians, NSE and ChrA blood
      levels did not correlate with progression free survival, disease specific
      survival, or MCC recurrence. We found CTC in 97% of tested MCC patients. CTC
      counts were elevated in patients with active disease, suggesting their potential
      use in monitoring MCC. CONCLUSIONS: NSE and ChrA levels were not effective in
      predicting outcomes or detecting recurrences of MCC. In contrast, CTC counts have
      potential utility as a biomarker for MCC disease behavior.

PMID- 26299617
TI  - Whole-transcriptome analysis of flow-sorted cervical cancer samples reveals that
      B cell expressed TCL1A is correlated with improved survival.
AB  - Cervical cancer is typically well infiltrated by immune cells. Because of the
      intricate relationship between cancer cells and immune cells, we aimed to
      identify both cancer cell and immune cell expressed biomarkers. Using a novel
      approach, we isolated RNA from flow-sorted viable EpCAM+ tumor epithelial cells
      and CD45+ tumor-infiltrating immune cells obtained from squamous cell cervical
      cancer samples (n = 24). Total RNA was sequenced and differential gene expression
      analysis of the CD45+ immune cell fractions identified TCL1A as a novel marker
      for predicting improved survival (p = 0.007). This finding was validated using
      qRT-PCR (p = 0.005) and partially validated using immunohistochemistry (p =
      0.083). Importantly, TCL1A was found to be expressed in a subpopulation of B
      cells (CD3-/CD19+/CD10+/CD34-) using multicolor immunofluorescence. A high
      TCL1A/CD20 (B cell) ratio, determined in total tumor samples from a separate
      patient cohort using qRT-PCR (n = 52), was also correlated with improved survival
      (p = 0.027). This is the first study demonstrating the prognostic value of
      separating tumor epithelial cells from tumor-infiltrating immune cells and
      determining their RNA expression profile for identifying putative cancer
      biomarkers. Our results suggest that intratumoral TCL1A+ B cells are important
      for controlling cervical cancer development. 

PMID- 26299619
TI  - Levels of physical activity among adults 18-64 years old in 28 European
      countries.
AB  - BACKGROUND: Sedentary lifestyle is associated with more than three million deaths
      annually. Data from the 2013 Eurobarometer survey were analyzed to assess levels
      of physical activity across the European Union (EU) and to explore factors
      associated with adequate and high physical activity. METHODS: A representative
      sample of n=19,978 individuals aged 18-64 years from the 28 EU countries (sub
      sample of the Eurobarometer survey, wave 80.2) was analyzed. Frequency and
      average duration of walking, moderate and vigorous physical activity was assessed
      with a self-reported questionnaire. Participants were then classified as
      physically inactive or adequately/highly active, based on the World Health
      Organization's (WHO) recommendations. The total amount of MET-minutes (MET-min)
      per week was also calculated for each respondent. RESULTS: The proportion of
      physically inactive individuals was 28.6%, (12.4% in Sweden to 53.7% in Cyprus),
      while 59.1% of the respondents (37.9% in Portugal and Cyprus to 72.2% in Sweden)
      were classified as highly active. The mean total weekly physical activity was
      2151 MET-min (95%CI: 2095-2206), of which 891 MET-min (95%CI: 858-924) were
      contributed by vigorous exercise, 559 MET-min (95%CI: 540-578) by moderate
      exercise (excluding walking) and 690 MET-min (95%CI: 673-706) by walking. Male
      gender, younger age, residence in rural areas and Northern Europe, higher
      education level and ability to pay bills were independently associated with
      higher physical activity. CONCLUSION: One fourth of the EU population did not
      meet the WHO's recommendations for physical activity, with wide inequalities
      between and within countries. Wide-reaching environmental approaches are required
      to promote physical activity and address these inequalities.

PMID- 26299618
TI  - CD44 promotes multi-drug resistance by protecting P-glycoprotein from FBXO21
      mediated ubiquitination.
AB  - Here we demonstrate that a ubiquitin E3-ligase, FBXO21, targets the multidrug
      resistance transporter, ABCB1, also known as P-glycoprotein (P-gp), for
      proteasomal degradation. We also show that the Ser291-phosphorylated form of the
      multifunctional protein and stem cell marker, CD44, inhibits FBXO21-directed
      degradation of P-gp. Thus, CD44 increases P-gp mediated drug resistance and
      represents a potential therapeutic target in P-gp-positive cells. 

PMID- 26299620
TI  - Young women's experiences of intrusive behavior in 12 countries.
AB  - The present study provides international comparisons of young women's (N = 1,734)
      self-reported experiences of intrusive activities enacted by men. Undergraduate
      psychology students from 12 countries (Armenia, Australia, England, Egypt,
      Finland, India, Indonesia, Italy, Japan, Portugal, Scotland, and Trinidad)
      indicated which of 47 intrusive activities they had personally experienced.
      Intrusive behavior was not uncommon overall, although large differences were
      apparent between countries when women's personal experiences of specific
      intrusive activities were compared. Correlations were carried out between self
      reported intrusive experiences, the Gender Empowerment Measure (GEM), and
      Hofstede's dimensions of national cultures. The primary associations were between
      women's experiences of intrusive behavior and the level of power they are
      afforded within the 12 countries. Women from countries with higher GEM scores
      reported experiencing more intrusive activities relating to courtship and
      requests for sex, while the experiences of women from countries with lower GEM
      scores related more to monitoring and ownership. Intrusive activities, many of
      them constituent of harassment and stalking, would appear to be widespread and
      universal, and their incidence and particular form reflect national level gender
      inequalities.

PMID- 26299621
TI  - Management of direct-acting antiviral agent failures.
AB  - Failure to respond to the approved combinations of multiple direct-acting
      antiviral agents is relatively low in hepatitis C virus treatment registration
      studies, with rates of 1% to 7%, depending on the patients' baseline
      characteristics. In real life, failure is slightly higher, likely because of
      lower compliance. Treatment failures are usually related to relapse and less
      often to on-treatment viral breakthrough. Hepatitis C drug-resistant variants are
      detected in most patients who do not achieve viral eradication. The risk of
      developing these variants depends on host- and virus-related factors, the
      properties of the drugs used, and the treatment strategies applied. Patients who
      carry resistance-associated variants may not obtain benefits from treatment and
      are at risk of disease progression and transmission of the variants. Whether
      hepatitis C resistance-associated variants persist depends on their type: NS3-4A
      variants often disappear gradually after therapy is stopped, whereas NS5A
      variants tend to persist for more than 2 years. The best way to prevent emergence
      of resistant variants is to eliminate the virus at the first treatment using
      highly potent antivirals with genetic barriers to resistance. In patients failing
      first-generation protease inhibitors, combination therapies with sofosbuvir and
      NS5 inhibitors have proven effective. Some salvage regimens can be shortened to
      12 weeks by addition of ribavirin. The optimal treatment for patients who fail an
      NS5A inhibitor and those with multidrug-resistant variants remains to be defined,
      and research efforts should continue to focus on treatment for these patients.

PMID- 26299622
TI  - MAPKAP kinase 2 regulates IL-10 expression and prevents formation of intrahepatic
      myeloid cell aggregates during cytomegalovirus infections.
AB  - BACKGROUND & AIMS: The kinase p38(MAPK) and its downstream target MAPKAP kinase
      (MK) 2 are critical regulators of inflammatory responses towards pathogens. To
      date, the relevance of MK2 for regulating IL-10 expression and other cytokine
      responses towards cytomegalovirus (CMV) infection and the impact of this pathway
      on viral replication in vitro and in vivo is unknown and the subject of this
      study. METHODS: The effect of MK2, interferon-alpha receptor (IFNAR)1,
      tristetraprolin (TTP) and IL-10 on mouse (M)CMV virus titres, cytokine
      expression, signal transduction, transcript stability, liver enzymes release,
      immune cell recruitment and aggregation in response to MCMV infection were
      studied ex vivo in hepatocytes and macrophages, as well as in vivo. RESULTS: MK2
      is critical for MCMV-induced production of IL-10, IFN-alpha2 and 4, IFN-beta, IL
      6, and TNF-alpha but not for IFN-gamma. The MCMV-induced IL-10 production
      requires activation of IFNAR1 and is further regulated by MK2 and TTP-dependent
      stabilization of IL-10 transcripts. MK2(-/-) mice are able to control acute MCMV
      replication, despite deregulated cytokine production. This may be related to the
      observation that MCMV-infected MK2(-/-) mice show enhanced formation of focal
      intrahepatic lymphocyte infiltrates resembling intrahepatic myeloid cell
      aggregates of T cell expansion (iMATEs), which were also observed in MCMV
      infected IL-10(-/-) mice but are almost absent in MCMV-infected wild-type
      controls. CONCLUSIONS: The data suggest that MK2 is critical for regulating
      cytokine responses towards acute MCMV infection, including that of IL-10 via
      IFNARI-mediated circuits. MCMV stimulates expression of MK2-dependent cytokines,
      in particular IL-10 and thereby prevents enhanced formation of intrahepatic iMATE
      like cellular aggregates.

PMID- 26299627
TI  - Factors influencing mortality and morbidity following colorectal resection in
      France. Analysis of a national database (2009-2011).
AB  - AIM: Correlation between outcome and hospital volume regarding colorectal
      resection (CRR) has been described, but it suggests that provider variability may
      have an impact. Our aim was to analyse the influence of institutional
      characteristics and the impact of volume [high volume (HV) or low volume (LV)] on
      mortality and morbidity after CRR at a national level. METHOD: Data from 2009
      2012, including patient demographics, diagnosis, procedure, mode of admission and
      discharge and hospital type, were obtained. Each hospital admission was
      classified as one of four levels of severity. RESULTS: Of 176,444 patients
      included, 5408 (3.06%) died and 41,240 (23.37%) had a complication. Multivariate
      analysis showed that factors influencing morbidity were age over 80 years,
      severity level, pathology other than diverticular disease, male gender, demanding
      surgery, open surgery and surgery in an HV institution. Factors influencing
      mortality were the same except for the impact of volume. In HV centres, surgery
      was significantly more demanding (54.66% vs 47.17%, P < 0.0001), morbidity more
      frequent (26.59% vs 22.07%, P < 0.0001), but mortality was lower (2.17% vs 3.43%,
      P < 0.0001). In total, 6038 (3.4%) patients were transferred after surgery.
      Transfer rate and mortality after transfer were significantly higher in LV
      institutions (respectively: 4.3% vs 2.5%, P < 0.0001; and 12% vs 10.3%, P <
      0.0001). CONCLUSION: High volume centres have higher morbidity, but lower
      mortality. Six per cent of patients in LV centres required transfer. A national
      mortality rate after CRR of 3.5% can be expected. Transfer rate and mortality
      after transfer should be included in the evaluation of institutional mortality.
      Volume of institution, regardless of type, influences mortality after CRR.

PMID- 26299628
TI  - Catabolite control protein A has an important role in the metabolic regulation of
      Streptococcus suis type 2 according to iTRAQ-based quantitative proteomic
      analysis.
AB  - The catabolite control protein A (ccpA) regulates the carbon metabolism in
      Streptococcus suis type 2 and has pleiotropic regulatory functions in bacterial
      virulence and transcription. The present study systematically investigated ccpA
      activity in Streptococcus suis type 2 using isobaric tag for relative and
      absolute quantification (iTRAQ) liquid chromatography-tandem mass spectrometry
      based proteomics. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes
      analyses demonstrated that ccpA is an important protein for the regulation of
      metabolism, virulence and immune pathways in Streptococcus suis type 2. The
      present study therefore expanded the current understanding of the effects of ccpA
      on virulence, metabolic regulation and transcription in Streptococcus suis type 2
      and other important pathogens.

PMID- 26299629
TI  - Efficacy of Varicocele Repair in Different Age Groups.
AB  - OBJECTIVE: To compare semen parameters and spouse pregnancy rates after
      varicocele repair in 2 age groups. MATERIALS AND METHODS: Mean changes in
      spermatozoa concentration, motility, and morphology after varicocele repair in 83
      patients were compared between patients aged 30 years or younger (group 1) and
      those older than 30 years (group 2). Spouse pregnancy rates were compared between
      the 2 age groups. RESULTS: The mean sperm concentration increased significantly
      in both groups (P <.05). The percentage of motile sperm increased from 48.2% to
      56.6% in group 1 and from 47.2% to 53.2% in group 2 one year after varicocele
      repair. The increase in motility was statistically significant for both groups (P
      <.05), but there was no statistically significant difference in the increase in
      sperm motility between the 2 groups (P = .01). The percentage of sperm with
      abnormal morphology decreased significantly in both groups 12 months
      postoperatively (from 62.7% to 59.6% in group 1 and from 61.3% to 58% in group 2;
      P = .03). However, there was no statistically significant difference in the
      improvement in sperm morphology between the 2 groups (P >.05). The pregnancy
      rates in the patients' spouses were 51.1% and 44.7% in groups 1 and 2,
      respectively. This difference was not statistically significant (P = .9).
      CONCLUSION: There was no statistically significant difference in semen parameter
      improvement and spouse pregnancy rates after varicocelectomy in the 2 age groups.

PMID- 26299630
TI  - Association Between Testosterone Supplementation Therapy and Thrombotic Events in
      Elderly Men.
AB  - OBJECTIVE: To determine the prevalence of thrombotic events and all-cause
      mortality in men older than 65 years with hypogonadism treated with testosterone
      therapy (TST). PATIENTS AND METHODS: We retrospectively reviewed the charts of
      217 hypogonadal men >65 years. We compared men who received TST (n = 153) to
      hypogonadal men (n = 64) who did not receive TST. We evaluated all-cause
      mortality, prevalence of myocardial infarction (MI), transient ischemic attack
      (TIA), cerebrovascular accident (CVA or "stroke"), and deep vein
      thrombosis/pulmonary embolism (DVT/PE). All events were verified by contacting
      patients. We excluded men with previous thrombotic events, men previously on
      androgen deprivation therapy, and men who had used TST before age of 65 years.
      RESULTS: Median age and Charlson Comorbidity Index of men on TST (74y; 5.1) was
      similar to hypogonadal men not on TST (73y, P = .48; 5.3, P = .36). Median follow
      up was 3.8 vs 3.5 years (TST vs no TST). No man on TST died, whereas 5
      hypogonadal men who did not receive TST died (P = .007). There were 4 thrombotic
      events (1 MI, 2 CVA/TIA, and 1 PE) in men who received TST and 1 event (CVA/TIA)
      among men who did not receive TST (P = .8). All events (1 death, 6-month follow
      up) occurred at least after 2 years of follow-up. CONCLUSION: There was increased
      all-cause mortality in hypogonadal men not treated with testosterone compared to
      men who received TST. There was no difference in prevalence of MI, TIA/CVA, or PE
      between patients treated with testosterone and hypogonadal men not treated with
      testosterone.

PMID- 26299631
TI  - Editorial Comment.

PMID- 26299632
TI  - Reply: To PMID 26299630.

PMID- 26299633
TI  - Halogen bonding assisted selective removal of bromide.
AB  - A new benzene platform based tripodal halogen bond (XB) donor receptor, 1a, has
      shown selectivity towards bromide over chloride and other interfering anions.
      Importantly, bromide selectivity of 1a has been utilized towards the selective
      removal of bromide (complex 1) from a mixture of interfering anions via a
      competitive crystallization process.

PMID- 26299634
TI  - Basal serum testosterone levels correlate with ovarian reserve and ovarian
      response in cycling women undergoing in vitro fertilization.
AB  - This study aimed to investigate the association between basal serum testosterone
      levels and in vitro fertilization (IVF) parameters in cycling women. A
      retrospective cohort study was performed at a clinical IVF center, and 495 women
      with regular menstruation were enrolled. Serum testosterone levels were measured
      before the start of IVF treatment cycle. We found that basal serum testosterone
      levels were negatively associated with female age and FSH/LH ratios. In contrast,
      we found a positive correlation between serum testosterone levels and the number
      of oocytes and available embryos. However, there was no significant association
      between testosterone levels and pregnancy outcome. Our results suggest that basal
      serum testosterone levels were significantly related to certain classic
      indicators of ovarian reserve, such as age and FSH/LH ratios. Increased
      testosterone levels improved ovarian response in cycling women, but they fail to
      predict pregnancy and miscarriage rate. 

PMID- 26299635
TI  - Combinatorial anticancer effects of curcumin and sorafenib towards thyroid cancer
      cells via PI3K/Akt and ERK pathways.
AB  - The objective of this study was to examine the in vitro combinatorial anticancer
      effects of curcumin and sorafenib towards thyroid cancer cells FTC133 using a MTT
      cytotoxicity assay, and to test whether the mechanism involves induction of
      apoptosis. The present results demonstrated that curcumin at 15-25 MUM dose
      dependently suppressed the proliferation of FTC133. Combined treatment (curcumin
      (25 MUM) and sorafenib (2 MUM)) resulted in a reduction in cell colony formation
      and significantly decreased the invasion and migration of FTC133 cells compared
      with that treated with individual drugs. Western blot showed that the levels of p
      ERK and p-Akt proteins were significantly reduced (p < 0.01) in the medicine
      treated FTC133 cells. The curcumin was found to dose-dependently inhibit the
      apoptosis of FTC133 cells possibly via PI3K/Akt and ERK pathways. There is a
      synergetic antitumour effect between curcumin and sorafenib. 

PMID- 26299636
TI  - Remote effects of extracorporeal shock wave therapy on cutaneous
      microcirculation.
AB  - BACKGROUND: Extracorporeal shock wave treatment (ESWT) has proven its clinical
      benefits in different fields of medicine. Tissue regeneration and healing is
      improved after shock wave treatment. Even in the case of burn wounds angiogenesis
      and re-epithelialization is accelerated, but ESWT in extensive burn wounds is
      impracticable. HYPOTHESIS: High energy ESWT influences cutaneous microcirculation
      at body regions remote from application site. METHODS: Eighteen Sprague Dawley
      rats were randomly assigned to two groups and received either high energy ESWT
      (Group A: total 1000 impulses, 10 J) or placebo shock wave treatment (Group B: 0
      impulses, 0 J), applied to the dorsal lower leg of the hind limb. Ten minutes
      later microcirculatory effects were assessed at the contralateral lower leg of
      the hind limb (remote body region) by combined Laser-Doppler-Imaging and
      Photospectrometry. RESULTS: In Group A cutaneous capillary blood velocity was
      significantly increased by 152.8% vs. placebo ESWT at the remote body location (p
      = 0.01). Postcapillary venous filling pressure remained statistically unchanged
      (p > 0.05), while cutaneous tissue oxygen saturation increased by 12.7% in Group
      A (p = 0.220). CONCLUSION: High energy ESWT affects cutaneous hemodynamics in
      body regions remote from application site in a standard rat model. The results of
      this preliminary study indicate that ESWT might be beneficial even in
      disseminated and extensive burn wounds by remote shock wave effects and should
      therefore be subject to further scientific evaluation.

PMID- 26299637
TI  - An efficient top-down approach for the fabrication of large-aspect-ratio g-C3N4
      nanosheets with enhanced photocatalytic activities.
AB  - Graphitic carbon nitride (g-C3N4) nanosheets with large aspect ratios were
      fabricated from bulk g-C3N4 through an efficient top-down approach of moderate
      disintegration-exfoliation using diluted H2SO4 as an "efficient knife". By prior
      disintegration in a diluted H2SO4 solution, the exfoliation of bulk g-C3N4 was
      effectively accelerated. The as-prepared g-C3N4 nanosheets possess a two
      dimensional (2D) thin-layer structure with seven-atom thickness, a large lateral
      size of about 1 MUm, and a high specific surface area of 80 m(2) g(-1). Compared
      with the bulk precursor, the g-C3N4 nanosheets showed much higher efficiency of
      photogenerated charge transfer and separation, and consequently exhibited
      enhanced photocatalytic activity toward hydrogen evolution and pollutant
      decomposition under both full-sunlight and visible-light irradiation. 

PMID- 26299638
TI  - The influence of errors during practice on motor learning in young individuals
      with cerebral palsy.
AB  - The aim of this study was to investigate the effect of errors during practice on
      motor skill learning in young individuals with cerebral palsy (CP). Minimizing
      errors has been validated in typically developing children and children with
      intellectual disabilities as a method for implicit learning, because it reduces
      working memory involvement during learning. The present study assessed whether a
      practice protocol that aims at minimizing errors can induce implicit learning in
      young individuals with CP as well. Accordingly, we hypothesized that reducing
      errors during practice would lead to enhanced learning and a decrease in the
      dependency of performance on working memory. Young individuals with CP practiced
      an aiming task following either an error-minimizing (N=20) or an error-strewn
      (N=18) practice protocol. Aiming accuracy was assessed in pre-, post- and
      retention test. Dual task performance was assessed to establish dependency on
      working memory. The two practice protocols did not invoke different amounts or
      types of learning in the participants with CP. Yet, participants improved aiming
      accuracy and showed stable motor performance after learning, irrespective of the
      protocol they followed. Across groups the number of errors made during practice
      was related to the amount of learning, and the degree of conscious monitoring of
      the movement. Only participants with relatively good working memory capacity and
      a poor initial performance showed a rudimentary form of (most likely, explicit)
      learning. These new findings on the effect of the amount of practice errors on
      motor learning in children of CP are important for designing interventions for
      children and adolescents with CP. 

PMID- 26299639
TI  - Impact of tactile function on upper limb motor function in children with
      Developmental Coordination Disorder.
AB  - This study investigated the presence of, and relationship between tactile
      dysfunction and upper limb motor function in children with Developmental
      Coordination Disorder (DCD) compared to typical developing (TD) children.
      Participants were 36 children aged 6-12 years. Presence of DCD (n=20) or TD
      (n=16) was confirmed using the Movement Assessment Battery for Children, second
      edition. All children participated in a comprehensive assessment of tactile
      registration (Semmes Weinstein Monofilaments); tactile spatial perception (Single
      Point Localisation (SPL) and two-point discrimination (2PD)); haptic perception
      (Stereognosis); speed of simple everyday manual tasks (Jebsen-Taylor Test of Hand
      Function (JTTHF)); and handwriting speed and accuracy (Evaluation Tool of
      Children's Handwriting (ETCH)). Compared to TD children, children with DCD
      demonstrated poorer localisation of touch in the non-dominant hand (p=0.04),
      slower speed of alphabet writing (p<0.05) and less legible handwriting (p<0.01),
      but no difference in speed of simple everyday manual tasks (JTTHF: p>0.05).
      Regression analysis showed that spatial tactile perception (SPL) predicted
      handwriting legibility (ETCH: r=0.11) and speed of functional tasks (JTTHF:
      r=0.33). These results suggest that tactile function, specifically single point
      localisation, should be a primary tactile assessment employed to determine
      reasons for upper limb motor difficulties experienced by children with DCD. 

PMID- 26299640
TI  - Types of fruits and vegetables used in commercial baby foods and their
      contribution to sugar content.
AB  - Fruits and vegetables (F&V) are often featured in names of commercial baby foods
      (CBFs). We aimed to survey all available CBFs in the UK market with F&V included
      in the food name in order to describe the amount and types of F&V used in CBF and
      their contribution to total sugar content. Food labels were used to identify F&V
      and total sugar content. Fruits were more common than vegetables in names of the
      329 CBFs identified. The six most common F&V in the names were all relatively
      sweet: apple, banana, tomato, mango, carrot and sweet potato. The percentage of
      F&V in the foods ranged from a median of 94% for sweet-spoonable to 13% for dry
      savoury products. Fruit content of sweet foods (n = 177) was higher than
      vegetable content of savoury foods (n = 152) with a median (IQR) of 64.0 g/100 g
      (33.0-100.0) vs. 46.0 g/100 g (33-56.7). Fruit juice was added to 18% of
      products. The proportion of F&V in CBF correlated significantly with sugar
      content for all the food types except dry-savoury food (sweet-spoonable r = 0.24,
      P = 0.006; savoury-spoonable r = 0.65, P < 0.001; sweet-dry r = 0.81, P < 0.001;
      savoury-dry r = 0.51, P = 0.06) and explained up to two-thirds of the variation
      in sugar content. The F&V content of CBFs mainly consists of fruits and
      relatively sweet vegetables which are unlikely to encourage preferences for
      bitter-tasting vegetables or other non-sweet foods. F&V contribute significantly
      to the total sugar content, particularly of savoury foods.

PMID- 26299641
TI  - Carbo-Iron as improvement of the nanoiron technology: From laboratory design to
      the field test.
AB  - In a first pilot-scale field test the use of Carbo-Iron(r) was successfully
      demonstrated. Carbo-Iron was developed with the goal to overcome significant
      shortcomings of nanoscale zero-valent iron (NZVI) for in-situ groundwater
      remediation. The composite material of colloidal activated carbon and embedded
      nanoiron structures has been tested for the remediation of a tetrachloroethene
      (PCE) contaminated field site in Lower Saxony, Germany. The results of the two
      step field test confirmed the properties intended by its design and the particle
      performance achieved in the laboratory experiments. The material showed transport
      lengths of several metres in the field and fast PCE decomposition with no vinyl
      chloride formation. Extended longevity of the PCE decrease in the treated area
      and evidence for microbiological participation were found. Carbo-Iron is now
      under study in the framework of the EU-project NanoREM where its performance is
      being further optimized at various scales from laboratory via large-scale tank to
      field testing. Targeted property adjustment was successful for Carbo-Iron
      performance in both directions: plume treatment and source attack. 

PMID- 26299642
TI  - Protective effects of germinated and fermented soybean extract against tert-butyl
      hydroperoxide-induced hepatotoxicity in HepG2 cells and in rats.
AB  - The aim of the current study is to investigate the antioxidant and
      hepatoprotective effects of germinated and fermented soybean extract (GFSE) on
      tert-butyl hydroperoxide (t-BHP)-induced oxidative stress in HepG2 cells and in
      the rat liver. High performance liquid chromatography (HPLC) analysis showed that
      genistin (3.40 +/- 0.14 MUg mg(-1)) was the most abundant isoflavone in the GFSE.
      Coumestrol (1.00 +/- 0.04 MUg mg(-1)), daidzin (0.78 +/- 0.14 MUg mg(-1)),
      genistein (0.68 +/- 0.05 MUg mg(-1)), glycitin (0.54 +/- 0.02 MUg mg(-1)),
      glycitein (0.41 +/- 0.02 MUg mg(-1)), and daidzein (0.02 +/- 0.0 g mg(-1)) are
      also contained in decreasing order of content. GFSE significantly inhibited t-BHP
      induced reactive oxygen species (ROS) production in HepG2 cells. This GFSE
      induced ROS reduction was associated with the down-regulation of nicotinamide
      adenine dinucleotide phosphate oxidase 4 (NOX4), a pro-oxidant enzyme, and the up
      regulation of the mRNA levels of antioxidant enzymes, including catalase,
      superoxide dismutase (SOD), glutathione reductase (GR), and glutathione
      peroxidase (Gpx) in the rat liver. In addition, increased levels of antioxidant
      enzyme mRNAs correlated with the enhanced enzymatic activities of SOD, catalase,
      and glutathione-S-transferase (GST). The antioxidant effect of GFSE was supported
      by the reduction in the levels of malondialdehyde (MDA), a hydroperoxide, and the
      serum levels of lactate dehydrogenase (LDH), a biomarker of cell damage, were
      also lowered by GFSE. Alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST), which are clinical biomarkers of liver function, were
      shown to be improved with GFSE administration. The effects of GFSE were
      attributable to an improvement in liver tissue morphology. Taken together, GFSE
      protected the liver from t-BHP-induced oxidative stress by regulating ROS-related
      enzymes. Our results suggest that GFSE might be a hepatoprotective source against
      oxidative stress. 

PMID- 26299643
TI  - Better adherence to antithyroid drug is associated with decreased risk of stroke
      in hyperthyroidism patients.
AB  - BACKGROUND: An increased risk for ischaemic stroke has been reported in young
      hyperthyroidism patients independent of atrial fibrillation (AF). However,
      whether the use of antithyroid drugs in hyperthyroidism patients can reduce the
      occurrence of ischaemic stroke remains unclear. METHODS: A total of 36,510 newly
      diagnosed hyperthyroidism patients during 2003-2006 were identified from the
      Taiwan National Health Insurance Research database. Each patient was individually
      tracked for 5 years from their index date (beginning the antithyroid drugs) to
      identify those who suffered from new episode of ischaemic stroke. Medication
      possession ratio (MPR) was used to represent the antithyroid drug compliance. The
      association between the MPR and the risk of stroke was examined. RESULTS: The
      stroke incidence rates for hyperthyroidism patients with age < 45 years and age
      >= 45 years were 0.42 and 3.76 per 1000 person-years, respectively. The patients
      aged < 45 years with MPR < 0.2 (adjusted hazard ratio, HR, 2.30; 95% CI, 1.13
      4.70; p = 0.02) and 0.2 <= MPR < 0.4 (adjusted HR, 2.24; 95% CI, 1.06-4.72; p =
      0.035) had a significantly increased risk of ischaemic stroke as compared to
      those with >= 0.6. In patients of the age >= 45 years, only the patients with MPR
      < 0.2 (adjusted HR, 1.44; 95% CI, 1.03-2.01; p = 0.036) had a significantly
      higher risk of ischaemic stroke as compared to those with MPR >= 0.6. In
      hyperthyroidism patients without AF, good antithyroid drugs compliance also
      reduced the incidence of stroke significantly (adjusted HR, range: 1.52-1.61; p =
      0.02); but not in hyperthyroidism with AF. CONCLUSION: Hyperthyroidism patients
      with good antithyroid drug compliance had a lower risk of ischaemic stroke than
      patients with poor compliance.

PMID- 26299644
TI  - Chimpanzee sociability is associated with vasopressin (Avpr1a) but not oxytocin
      receptor gene (OXTR) variation.
AB  - The importance of genes in regulating phenotypic variation of personality traits
      in humans and animals is becoming increasingly apparent in recent studies. Here
      we focus on variation in the vasopressin receptor gene 1a (Avpr1a) and oxytocin
      receptor gene (OXTR) and their effects on social personality traits in
      chimpanzees. We combine newly available genetic data on Avpr1a and OXTR allelic
      variation of 62 captive chimpanzees with individual variation in personality,
      based on behavioral assessments. Our study provides support for the positive
      association of the Avpr1a promoter region, in particular the presence of DupB,
      and sociability in chimpanzees. This complements findings of previous studies on
      adolescent chimpanzees and studies that assessed personality using questionnaire
      data. In contrast, no significant associations were found for the single
      nucleotide polymorphism (SNP) ss1388116472 of the OXTR and any of the personality
      components. Most importantly, our study provides additional evidence for the
      regulatory function of the 5' promoter region of Avpr1a on social behavior and
      its evolutionary stable effect across species, including rodents, chimpanzees and
      humans. Although it is generally accepted that complex social behavior is
      regulated by a combination of genes, the environment and their interaction, our
      findings highlight the importance of candidate genes with large effects on
      behavioral variation. 

PMID- 26299646
TI  - Simplified high-throughput screening of AOX1-expressed laccase enzyme in Pichia
      pastoris.
AB  - The heterologous protein expression in Pichia pastoris under the control of
      alcohol oxidase (AOX1)promoter comprises two steps, the growth and induction
      phases, which are time-consuming and technically demanding. Here, we describe an
      alternate method where expression is carried out directly in the methanol
      containing medium. Using this method, we were successful in screening high
      activity laccase clones from a library of laccase mutants generated by random
      mutagenesis. This simplified method not only saves time but also is highly
      efficient and can be used for screening a large number of clones. 

PMID- 26299645
TI  - Detecting respiratory viral RNA using expanded genetic alphabets and self
      avoiding DNA.
AB  - Nucleic acid (NA)-targeted tests detect and quantify viral DNA and RNA
      (collectively xNA) to support epidemiological surveillance and, in individual
      patients, to guide therapy. They commonly use polymerase chain reaction (PCR) and
      reverse transcription PCR. Although these all have rapid turnaround, they are
      expensive to run. Multiplexing would allow their cost to be spread over multiple
      targets, but often only with lower sensitivity and accuracy, noise, false
      positives, and false negatives; these arise by interactions between the multiple
      nucleic acid primers and probes in a multiplexed kit. Here we offer a multiplexed
      assay for a panel of respiratory viruses that mitigates these problems by
      combining several nucleic acid analogs from the emerging field of synthetic
      biology: (i) self-avoiding molecular recognition systems (SAMRSs), which
      facilitate multiplexing, and (ii) artificially expanded genetic information
      systems (AEGISs), which enable low-noise PCR. These are supplemented by
      "transliteration" technology, which converts standard nucleotides in a target to
      AEGIS nucleotides in a product, improving hybridization. The combination supports
      a multiplexed Luminex-based respiratory panel that potentially differentiates
      influenza viruses A and B, respiratory syncytial virus, severe acute respiratory
      syndrome coronavirus (SARS), and Middle East respiratory syndrome (MERS)
      coronavirus, detecting as few as 10 MERS virions in a 20-MUl sample. 

PMID- 26299647
TI  - Studying the relationship between cell cycle and Alzheimer's disease by gold
      nanoparticle probes.
AB  - In this study, a simple gold nanoparticle (GNP)-based colorimetric assay has been
      developed for studying the relationship between cell cycle and beta-amyloid
      peptide (Abeta, the biomarker of Alzheimer's disease [AD]) expression level. It
      was found that Abeta expression of neuronal cells (e.g., SHG-44 cell line) is
      strongly dependent on cell cycle phases; that is, the Abeta expression level was
      highest when cells were arrested in the G1/S phase by thymidine and was lowest
      when they were arrested in the G2/M phase by nocodazole. This finding may improve
      the understanding of AD pathology and provide a new tool for anti-dementia drug
      development. 

PMID- 26299648
TI  - Knockdown of juvenile hormone acid methyl transferase severely affects the
      performance of Leptinotarsa decemlineata (Say) larvae and adults.
AB  - BACKGROUND: Juvenile hormone (JH) plays a critical role in the regulation of
      metamorphosis in Leptinotarsa decemlineata, a notorious defoliator of potato. JH
      acid methyltransferase (JHAMT) is involved in one of the final steps of JH
      biosynthesis. RESULTS: A putative JHAMT cDNA (LdJHAMT) was cloned. Two double
      stranded RNAs (dsRNAs) (dsJHAMT1 and dsJHAMT2) against LdJHAMT were constructed
      and bacterially expressed. Experiments were conducted to investigate the
      effectiveness of RNAi in both second- and fourth-instar larvae. Dietary
      introduction of dsJHAMT1 and dsJHAMT2 successfully knocked down the target gene,
      lowered JH titre in the haemolymph and reduced the transcript of Kruppel
      homologue 1 gene. Ingestion of dsJHAMT caused larval death and weight loss,
      shortened larval developmental period and impaired pupation. Moreover, the
      dsJHAMT-fed pupae exhibited lower adult emergence rates. The resulting adults
      weighed an average of 50 mg less than the control group, and the females did not
      deposit eggs. Application of pyriproxyfen to the dsJHAMT-fed insects rescued all
      the negative effects. CONCLUSIONS: LdJHAMT expresses functional JHAMT enzyme. The
      RNAi targeting LdJHAMT could be used for control of L. decemlineata. (c) 2015
      Society of Chemical Industry.

PMID- 26299649
TI  - Methods matter for critical reviews too.

PMID- 26299650
TI  - On tasks and cognitive constructs for the bilingual (non-)advantage.

PMID- 26299651
TI  - Erythrodermic mycosis fungoides and Sezary syndrome treated with extracorporeal
      photopheresis as part of a multimodality regimen: A single-centre experience.
AB  - BACKGROUND: Extracorporeal photopheresis (ECP) is recommended for the
      erythrodermic mycosis fungoides (MF) and Sezary syndrome (SS) alone or in
      combination with other therapies. The possibility of a differential response in
      the blood and skin has hardly been addressed in the literature. OBJECTIVES: To
      evaluate the clinical response rate of patients with erythrodermic MF and SS to
      ECP as part of a multimodality approach and to compare the kinetics of the blood
      and skin responses in the presence of leukaemic involvement. METHODS: Twenty
      patients were treated with ECP and other modalities at a tertiary medical centre
      in 2003-2013. Ten patients had SS, 1 CD8-positive patch-stage MF with leukaemic
      involvement and nine erythrodermic MF. Clinical and outcome data were collected
      retrospectively from the medical files. Response was evaluated overall and for
      blood and skin separately. RESULTS: Adjunctive therapies were interferon-alpha,
      narrow-band ultraviolet B, psoralen and ultraviolet A, isotretinoin, acitretin,
      methotrexate, prednisone, topical nitrogen mustard and total skin or localized
      hands/feet electron beam radiotherapy. Overall response was documented in 13
      patients (65%)--complete 30%, partial 35%--and maintained for >2 years in 38.5%.
      In patients with leukaemic involvement (n = 11), the blood response occurred
      earlier than skin response (P = 0.008) and was maintained longer (P = 0.03). In
      three of the patients with a complete blood response, the skin response was
      partial (n = 2) or absent (n = 1). CONCLUSION: Extracorporeal photopheresis as
      part of a multimodality approach yields a high durable clinical response in
      patients with erythrodremic MF and SS. The kinetics of the response differ
      between the blood and skin. The blood response occurs earlier and lasts longer;
      it does not necessarily predict the clinical skin response. Further studies are
      needed to determine if there is a survival advantage to a blood response in the
      absence of a skin response.

PMID- 26299652
TI  - Acknowledge, repeat, rephrase, elaborate: Witnesses can help each other remember
      more.
AB  - Crimes are often observed by multiple witnesses. Research shows that witnesses
      can contaminate each other's memory, but potential benefits of co-witness
      discussion have not yet been investigated. We examined whether witnesses can help
      each other remember, or prune each other's errors. In a research design with high
      ecological validity, attendees of a theatre play were interviewed approximately
      one week later about a violent scene in the play. The couples that signed up for
      our study had known each other for 31 years on average. Participants were first
      interviewed individually and then took part in a collaborative interview. We also
      included a control condition in which participants took part in two individual
      interviews. Collaboration did not help witnesses to remember more about the
      scene, but collaborative pairs made significantly fewer errors than nominal
      pairs. Further, quantitative and qualitative analyses of retrieval strategies
      during the discussion revealed that couples who actively acknowledged, repeated,
      rephrased, and elaborated upon each other's statements remembered significantly
      more information overall. Taken together, our findings suggest that, under
      certain circumstances, discussion between witnesses is not such a bad idea after
      all. 

PMID- 26299653
TI  - The ecological success of a social parasite increases with manipulation of
      collective host behaviour.
AB  - Many parasites alter the behaviour of their host to their own advantage, yet
      hosts often vary in their susceptibility to manipulation. The ecological and
      evolutionary implications of such variation can be profound, as resistant host
      populations may suffer lower parasite pressures than those susceptible to
      manipulation. To test this prediction, we assessed parasite-induced aggressive
      behaviours across 16 populations of two Temnothorax ant species, many of which
      harbour the slavemaker ant Protomognathus americanus. This social parasite uses
      its Dufour's gland secretions to manipulate its hosts into attacking nestmates,
      which may deter defenders away from itself during invasion. We indeed find that
      colonies that were manipulated into attacking their Dufour-treated nestmates were
      less aggressive towards the slavemaker than those that did not show slavemaker
      induced nestmate attack. Slavemakers benefited from altering their hosts'
      aggression, as both the likelihood that slavemakers survived host encounters and
      slavemaker prevalence in ant communities increased with slavemaker-induced
      nestmate attack. Finally, we show that Temnothorax longispinosus colonies were
      more susceptible to manipulation than Temnothorax curvispinosus colonies. This
      explains why T. curvispinosus colonies responded with more aggression towards
      invading slavemakers, why they were less likely to let slavemakers escape and why
      they were less frequently parasitized by the slavemaker than T. longispinosus.
      Our findings highlight that large-scale geographic variation in resistance to
      manipulation can have important implications for the prevalence and host
      preference of parasites. 

PMID- 26299654
TI  - Comparative mitochondrial genome analysis of Pythium insidiosum and related
      oomycete species provides new insights into genetic variation and phylogenetic
      relationships.
AB  - Oomycetes are eukaryotic microorganisms, which are phylogenetically distinct from
      the true-fungi, which they resemble morphologically. While many oomycetes are
      pathogenic to plants, Pythium insidiosum is capable of infecting humans and
      animals. Mitochondrial (mt) genomes are valuable genetic resources for exploring
      the evolution of eukaryotes. During the course of 454-based nuclear genome
      sequencing, we identified a complete 54.9 kb mt genome sequence, containing 2
      large inverted repeats, from P. insidiosum. It contains 65 different genes
      (including 2 ribosomal RNA genes, 25 transfer RNA genes and 38 genes encoding
      NADH dehydrogenases, cytochrome b, cytochrome c oxidases, ATP synthases, and
      ribosomal proteins). Thirty-nine of the 65 genes have two copies, giving a total
      of 104 genes. A set of 30 conserved protein-coding genes from the mt genomes of
      P. insidiosum, 11 other oomycetes, and 2 diatoms (outgroup) were used for
      phylogenetic analyses. The oomycetes can be classified into 2 phylogenetic
      groups, in relation to their taxonomic lineages: Saprolegnialean and
      Peronosporalean. P. insidiosum is more closely related to Pythium ultimum than
      other oomycetes. In conclusion, the complete mt genome of P. insidiosum was
      successfully sequenced, assembled, and annotated, providing a useful genetic
      resource for exploring the biology and evolution of P. insidiosum and other
      oomycetes.

PMID- 26299655
TI  - Polymorphism - 116C/G of the human X box binding protein 1 gene is associated
      with risk of type 2 diabetes in a Chinese Han population.
AB  - Evidence has been obtained showing that endoplasmic reticulum (ER) stress is
      closely associated with the development of type 2 diabetes (T2D) and that the
      human X box binding protein 1 (XBP1) is an important transcription factor
      involved in the development of ER stress. The study aimed to analyze the
      potential association between polymorphism -116C/G of XBP1 and the risk of T2D.
      The association between XBP1 polymorphism -116C/G and T2D risk was assessed among
      1058 consecutive unrelated subjects, including 523 T2D patients and 535 healthy
      controls, in a case control study. The -116GG genotype and -116G allele were more
      frequent in T2D subjects compared with control subjects by statistical analysis,
      showing that the -116GG homozygote polymorphism of XBP1 might lead to increased
      susceptibility to T2D in a Chinese Han population. T2D subjects with the -116GG
      genotype had higher fasting plasma glucose levels, fasting insulin levels, and
      HbA1c and worse HOMA-IR than the T2D subjects with -116CG and -116CC genotypes
      (P<0.0001). The study supports a role for -116C/G polymorphism of the XBP1
      promoter in the pathogenesis of T2D in a Chinese Han population, and more studies
      are needed to further evaluate our results. 

PMID- 26299656
TI  - SP1 and USF differentially regulate ADAMTS1 gene expression under normoxic and
      hypoxic conditions in hepatoma cells.
AB  - ADAM metallopeptidase with thrombospondin type I motif, 1 (ADAMTS1) that has both
      antiangiogenic and aggrecanase activity was dysregulated in many pathophysiologic
      circumstances. However, there is limited information available on the
      transcriptional regulation of ADAMTS1 gene. Therefore, this study mainly aimed to
      identify regulatory regions important for the regulation of ADAMTS1 gene under
      normoxic and hypoxic conditions in human hepatoma cells (HEP3B). Cultured HEP3B
      cells were exposed to normal oxygen condition, and Cobalt chloride (CoCl2)
      induced the hypoxic condition, which is an HIF-1 inducer. The cocl2-induced
      hypoxic condition led to the induced ADAMTS1 mRNA and protein expression in
      Hepatoma cells. Differential regulation of SP1 and USF transcription factors on
      ADAMTS1 gene expression was determined by transcriptional activity, mRNA and
      protein level of ADAMTS1 gene. Ectopic expression of SP1 and USF transcription
      factors resulted in the decrease in ADAMTS1 transcriptional activity of all
      promoter constructs consistent with mRNA and protein level in normoxic condition.
      However, overexpression of SP1 and USF led to the increase of ADAMTS1 gene
      expressions at mRNA and protein level in hypoxic condition. On the other hand,
      C/EBPalpha transcription factor didn't show any statistically significant effect
      on ADAMTS1 gene expression at mRNA, protein and transcriptional level under
      normoxic and hypoxic condition.

PMID- 26299657
TI  - Expression of stem cell pluripotency factors during regeneration in the earthworm
      Eisenia foetida.
AB  - Stem cell pluripotency factors can induce somatic cells to form induced
      pluripotent stem cells, which are involved in cell reprogramming and
      dedifferentiation. The tissue regeneration in the earthworm Eisenia foetida may
      involve cell dedifferentiation. There is limited information about associations
      between pluripotency factors and the regeneration. In this report, cDNA sequences
      of pluripotency factors, oct4, nanog, sox2, c-myc and lin28 genes from the
      earthworm E. foetida were cloned, and quantitative PCR analysis was performed for
      their mRNA expressions in the head, clitellum and tail. The maximum up-regulation
      of oct4, nanog, sox2, c-myc and lin28 occurred at 12h, 4 days, 12h, 2 days, and
      24h after amputation for 110, 178, 21, 251 and 325-fold, respectively, in
      comparison with the controls. The results suggest that the tissues are
      regenerated via cellular dedifferentiation and reprogramming.

PMID- 26299658
TI  - Drug-carrier interaction analysis in the cell penetrating peptide-modified
      liposomes for doxorubicin loading.
AB  - Doxorubicin (DOX) is widely used as an antitumor model drug in liposomes because
      of its high encapsulation efficiency. The cell-penetrating peptide (CPP) has
      potential applications in drug delivery systems. However, we discovered that the
      encapsulation efficiency of DOX decreased with increasing modification density of
      CPP on liposomes. To explore the interaction mechanisms of CPP-modified liposomes
      (CPPL) for DOX loading, X-ray diffraction, Fourier transform infrared
      spectroscopy and Raman spectroscopy were utilised, and theoretical calculations
      based on molecular dynamics simulation were performed. Results showed that the
      monomeric intermolecular interaction between CPP and DOX, in which the
      guanidinium group of CPP was parallel to the planar aromatic chromophore of DOX,
      depending on the cation-pi interaction and hydrogen bonds, weakened the tendency
      of DOX transporting into the internal medium from the liposomal external medium.
      Analysis of the interaction between CPP and DOX at the molecular level provided
      theoretical guidance for the further development of CPPL. 

PMID- 26299659
TI  - The Induction and Repair of DNA Interstrand Crosslinks and Implications in Cancer
      Chemotherapy.
AB  - DNA interstrand crosslinks (ICLs) can be induced by numerous endogenous and
      exogenous chemical agents with the capacity of covalently binding to two base
      sites in the two strands of the DNA duplex. A series of normal DNA metabolism
      processes are affected by ICLs. For example, DNA replication and transcription
      are interfered during cell division, which is fatal to cell survival. In cancer
      cells, the induction of ICLs is a significant target for cancer chemotherapies.
      However, the formation of ICLs in cancer cells can be weakened by the repair
      mechanisms of DNA damage, which results in resistance to chemotherapies.
      Therefore, it is necessary to develop highly effective ICL agents for the purpose
      of achieving good chemotherapeutic effects. Furthermore, the combination of ICL
      agents with inhibitors of ICL repair is a promising strategy for the clinical
      treatment of cancer. This review summarizes the development of several types of
      ICL agents as chemotherapies over the past decades and the mechanisms underlying
      the repair of DNA ICLs. The potential of ICL repair inhibitors for combination
      therapy with ICL agents in cancer treatment is also discussed. 

PMID- 26299660
TI  - Multiple Pharmacological Properties of a Novel Parthenin Analog P16 as Evident by
      its Cytostatic and Antiangiogenic Potential Against Pancreatic Adenocarcinoma
      PANC -1 Cells.
AB  - Pancreatic ductal adenocarcinoma (PDA) remains one of the deadliest types of
      cancers. Median survival rate is very poor with the currently available
      chemotherapeutical regimens. Therefore, discovery of new antineoplastic agents
      against PDA is one of the focused areas of contemporary research. The present
      study was undertaken to explore the antitumour activity of a potent parthenin
      analog P16. Among PANC-1, Mia PaCa-2 and AsPC-1 pancreatic cancer cells, PANC-1
      showed highest sensitivity to P16 with an IC50 value of 3.4 MUM. Time dependent
      cell cycle studies revealed that P16 suppressed the growth of PANC-1 cells by
      arresting the progression through the cell cycle in G2/M phase via downregulation
      of cyclin B1 and cyclin A. However, P16 did not alter the expressions of CDK-1
      and CDC25C in PANC-1 cells. The P16 induced cell cycle arrest, which
      consequently, led to induction of apoptosis, which was accompanied by activation
      of caspase-9 and -3. Interestingly, PANC-1 cells displayed increasing loss of
      mitochondrial potential, which seemed to be correlated to the activation of
      caspase-3. Additionally, P16 was also able to down-regulate the cell migration in
      PANC-1 cells. Furthermore, P16 treatment of hypoxic PANC-1 cells strongly
      suppressed the expression of proangiogenic factors VEGFR-2, HIF1alpha and
      HIF1beta. Antiangiogenic ability of P16 was also reflected in the human umbilical
      vascular endothelial cells (HUVECs), where it effectively suppressed the
      migration and inhibited the formation of the tube in a matrigel based assay.
      Therefore, cytostatic and antiangiogenic properties of P16 against pancreatic
      adenocarcinoma cells make it a suitable candidate for further investigation.

PMID- 26299661
TI  - The Immune System in Cancer Prevention, Development and Therapy.
AB  - The immune system plays a pivotal role in the maintenance of the integrity of an
      organism. Besides the protection against pathogens, it is strongly involved in
      cancer prevention, development and defense. This review focuses on how the immune
      system protects against infections and trauma and on its role in cancer
      development and disease. Focus is set on the interactions of the innate and
      adaptive immune system and tumors. The role of IFN-gamma as a pleiotropic
      cytokine that plays a very important role at the interface of innate and adaptive
      immune systems in tumor development and induction of anti-tumor immune responses
      is outlined. Further, immune cells as prognostic and predictive markers of cancer
      will be discussed. Data are provided that even the brain as immune privileged
      organ is subjected to immune surveillance and consequently also brain tumors.
      Immune therapeutic approaches for glioblastoma multiforme, the most frequent and
      malignant brain tumor, based on vaccination with dendritic cells are outlined and
      application of hyperthermia in form of magnetic nanoparticles is discussed. We
      conclude that the immune system and developing tumors are intimately intertwined.
      Anti-tumor immune responses can be prominently boosted by multimodal therapies
      aiming on the one hand to induce immunogenic tumor cell death forms and on the
      other hand to actively counteract the immune suppressive microenvironment based
      on the tumor itself. 

PMID- 26299662
TI  - Therapeutic Use of MicroRNAs in Cancer.
AB  - MicroRNAs are small non-coding RNAs which regulate gene expression and silence a
      wide set of target genes. Aberrant miRNA expression has been described in cancer
      cells and is at least in part responsible of cancer initiation, development and
      progression. Due to their role, miRNAs have emerged as therapeutic targets or
      molecules suitable at the therapeutic level as well as markers of the response to
      chemo/radio/targeted therapy. Restoration or repression of miRNAs expression and
      activity shows high potential in managing cancer, and many studies on pre
      clinical models have demonstrated the feasibility and efficacy of miRNA-based
      therapy. However, despite the exciting potential, some limitations, due to the
      degree of delivery and biodistribution or to possible side effects, need to be
      taken into consideration and solved in order to accomplish transition to clinical
      application. In this review we report and discuss the role of miRNAs in cancer,
      focusing on their use as therapeutic agents and their involvement in
      modulating/affecting the response to chemo/radio/targeted therapy in some of the
      most frequent solid tumors. 

PMID- 26299663
TI  - CXCR4 and Glioblastoma.
AB  - This article focuses on the possible application of antagonists of the G-protein
      coupled chemokine receptor, CXCR4, for the treatment of glioblastoma and
      summarises the evidence for CXCR4 antagonism being a viable therapeutic approach.
      Particular attention is paid to the role of this receptor in cancer stem cell
      biology, and the maintenance of CXCR4 expression by the glioblastoma key driver
      mutations. The expression of the CXCR4 receptor, and of its ligand stromal
      derived factor 1 (SDF-1, CXCL12), is maintained by intracellular pathways via
      positive feedback loops, and is associated with the epithelial mesenchymal
      transition (EMT) and the generation and self-renewal of cancer stem cells. SDF-1
      and CXCR4 also play a role in the generation and maintenance of the perivascular
      stem cell niche which contains these cancer stem cells. The available data
      suggest that most, if not all, glioblastoma cancer stem cells rely on CXCR4
      mediated signalling to maintain their phenotype. SDF-1 and CXCR4 are alsoinvolved
      in many other aspects of brain tumour biology including resistance to radio- and
      chemotherapy, the migration of cancer cells through the brain, the generation of
      the tumour blood supply and the recruitment of vascular progenitor cells. These
      properties suggest that a CXCR4 antagonist would help in the control of this
      disease. 

PMID- 26299664
TI  - Nutrition, Nitrogen Requirements, Exercise and Chemotherapy-Induced Toxicity in
      Cancer Patients. A puzzle of Contrasting Truths?
AB  - Amino acids can modulate cell metabolism and control cell fate by regulating cell
      survival and cell death. The molecular mechanisms involved are mediated by the
      mTOR complexes mTORC1 and mTORC2 activity. These complexes are finely regulated
      and the continuous advancement of the knowledge on their composition and function
      is revealing that their balance may represent the condition that determines the
      cell fate. This is important for normal healthy cells but it is becoming clear,
      and it is even more important, that the balance of the mTORCs activity may also
      condition the cell fate of cancer cells. Here, we discuss the evidences
      supporting the amino acids supplementation as a cancer fighting weapon and a
      possible strategy to counteract the myocyte toxicity associated with
      chemotherapy, possibly by tipping the balance of mTORCs activity. 

PMID- 26299665
TI  - MicroRNA-31 inhibits lung adenocarcinoma stem-like cells via down-regulation of
      MET-PI3K-Akt signaling pathway.
AB  - Accumulated evidences suggested that microRNAs (miRs) play an important role in
      non-small cell lung cancer (NSCLC). However, how miRs perform their functions in
      lung adenocarcinoma cancer stem cells (CSCs) remains unknown. Notably, most
      studies pay more attention to the effects of miRNAs on the metastasis traits
      whereas the growth activities of CSCs are rather undervalued. In our report,
      using A549CD133+cells, we examined the inhibitory effects and the underlying
      mechanisms of microRNA-31 (miR-31) on the growth of lung adenocarcinoma CSC-like
      cells. Initially, we determined the level of miR-31 in A549 and A549CD133+ cells.
      Over-expression of miR-31 was found in A549CD133+ cells by microarray and real
      time quantitative PCR (RTqPCR) assays. Experiments in multiple NSCLC cell lines
      in vitro and A549CD133+ cells xenograft models in vivo confirmed that down
      regulation of miR-31 resulted in increase of A549CD133+ cells growth, whereas
      overexpression of miR-31 led to the inhibition of adenocarcinoma cell
      proliferation. Also, MET proto-oncogene has been determined to be a direct target
      of miR-31 by dual luciferase report, RT-qPCR and western blot analysis. Down
      regulation of MET inhibited viability of A549CD133+ cells. The levels of
      PI3Kinase, Akt and p-Akt as well as downstream proteins were consequently
      decreased. These results suggest that miR-31 might inhibit the growth of lung
      adenocarcinoma cancer stem-like cells via down regulation of the MET-PI3K-Akt
      signaling pathway. 

PMID- 26299666
TI  - Differential Gene Expression of BRCA1,ERBB2 and TP53 biomarkers between Human
      Breast Tissue and Peripheral Blood Samples of Breast Cancer.
AB  - Breast cancer is a most common malignancy especially in Iraqi women accounting
      for high morbidity and mortality. Mutations in BRCA1 gene is one of the important
      genetic predisposing factors inbreast cancer. Similarly ERBB2 and TP53 are also
      key prognostic markers in breast cancer treatment.We were interested to explore
      the gene expression profiles of BRCA1, ERBB2 and TP53 in breast cancer women
      patients from Iraq so as to assess the potential of such markers in breast cancer
      treatment. The mRNA levels were significantly over-expressed in tumor tissues in
      comparison to normal ones with p values (p<0.005) observed between malignant
      BRCA1 and control tissue samples. Similarly significant difference (p<0.001) was
      observed between malignant ERBB2 in comparison to control, and malignant TP53 and
      benign tissue samples as well. However in blood samples, no considerable
      expression of these markers was observed. Out of three selected genes, ERBB2
      expression was significantly expressed in comparison to BRCA1 and TP53 in cancer
      tissue. Mutation analysis of BRCA1, ERBB2 and TP53 has been made to find out the
      region most susceptible to mutations in these genes The BRCA1 exon 11, ERBB2 16
      and TP53 exon 5 displayed increased chances of having mutations. We can conclude
      from the study that differential gene expression of BRCA1, ERBB2 and TP53 at mRNA
      levels may act as a diagnostic marker of circulating tumor cells having important
      prognostic value in breast cancer patients. 

PMID- 26299667
TI  - (14)N overtone transition in double rotation solid-state NMR.
AB  - Solid-state NMR transitions involving outer energy levels of the spin-1 (14)N
      nucleus are immune, to first order in perturbation theory, to the broadening
      caused by the nuclear quadrupole interaction. The corresponding overtone spectra,
      when acquired in conjunction with magic-angle sample spinning, result in lines,
      which are just a few kHz wide, permitting the direct detection of nitrogen
      compounds without the need for labeling. Despite the success of this technique,
      "overtone" resonances are still broadened due to indirect, second order effects
      arising from the large quadrupolar interaction. Here we demonstrate that another
      order of magnitude in spectral resolution may be gained by using double rotation.
      This brings the width of the (14)N solid-state NMR lines much closer to the
      region commonly associated with high-resolution solid-state NMR spectroscopy of
      (15)N and demonstrates the improvements in resolution that may be possible
      through the development of pulsed methodologies to suppress these second order
      effects. 

PMID- 26299669
TI  - Accessing conjugated polymers with precisely controlled heterobisfunctional chain
      ends via post-polymerization modification of the OTf group and controlled Pd(0)/t
      Bu3P-catalyzed Suzuki cross-coupling polymerization.
AB  - A general strategy toward the synthesis of well-defined conjugated polymers with
      controlled heterobisfunctional chain ends via combination of controlled Pd(0)/t
      Bu3P Suzuki cross-coupling polymerization with the post-polymerization
      modification of the triflate (OTf) group was disclosed. 

PMID- 26299668
TI  - Inhibition of microRNA-30a prevents puromycin aminonucleoside-induced podocytic
      apoptosis by upregulating the glucocorticoid receptor alpha.
AB  - It is well-established that steroid-resistant nephrotic syndrome commonly
      involves podocytic injury, however, the underlying mechanism remains to be
      elucidated. Previous studies have demonstrated that glucocorticoids enhance
      podocytic recovery predominantly through the functional isoform, glucocorticoid
      receptor (GR)alpha. Our previous study demonstrated the reduced expression of
      GRalpha in podocytes from patients with steroid-resistant nephrotic syndrome
      compared with those with steroid-sensitive syndromes, which suggested that
      microRNAs (miRNAs) may be a potential therapeutic target in the modulation of
      steroid sensitivity. The present study screened miRNAs in murine injured
      podocytes by microarray and identified 10 miRNAs significantly upregulated,
      including miR-30a, miR-30d, miR-100, miR181c, miR-5099, miR-3535, miR-140-3p, miR
      148-3p and miR-103-3p. Bioinformatic target prediction indicated that the GR was
      a candidate target gene of miR-30a. The data also indicated that miR-30a
      negatively regulated GRalpha in normal and injured podocytes induced by puromycin
      aminonucleoside (PAN). In addition, the inhibition of miR-30a prevented podocytic
      apoptosis induced by PAN. However, luciferase reporter assay data suggested an
      indirect effect on the transcriptional activity of GRalpha. The present study
      indicated that silencing of miR-30a may improve steroid sensitivity in injured
      podocytes, although the mechanism cannot be explained by conventional means and
      remains to be elucidated.

PMID- 26299670
TI  - Orientation, interaction and laser assisted self-assembly of organic single
      crystal micro-sheets in a nematic liquid crystal.
AB  - Colloidal self-assembly has been one of the major driving themes in material
      science to obtain functional and advanced optical materials with complex
      architecture. Most of the nematic colloids reported so far are based on the
      optically isotropic spherical microparticles. We study organic single crystal
      micro-sheets and investigate their orientation, interaction and directed assembly
      in a nematic liquid crystal. The micro-sheets induce planar surface anchoring of
      the liquid crystal. The elasticity mediated pair interaction of micro-sheets
      shows quadrupolar characteristics. The average orientation angle of the micro
      sheets in a planar cell and the angle between two micro-sheets in a homeotropic
      cell are supported by the Landau-de Gennes Q-tensor modeling. The self-assembly
      of the micro-sheets is assisted by a laser tweezer to form larger two-dimensional
      structures which have the potential for application of colloids in photonics. 

PMID- 26299672
TI  - Previously Uncultured Marine Bacteria Linked to Novel Alkaloid Production.
AB  - Low-nutrient media and long incubation times facilitated the cultivation of 20
      taxonomically diverse Gram-negative marine bacteria within the phyla
      Bacteroidetes and Proteobacteria. These strains comprise as many as three new
      families and include members of clades that had only been observed using culture
      independent techniques. Chemical studies of the type strains representing two new
      families within the order Cytophagales led to the isolation of nine new alkaloid
      secondary metabolites that can be grouped into four distinct structure classes,
      including azepinones, aziridines, quinolones, and pyrazinones. Several of these
      compounds possess antibacterial properties and appear, on structural grounds, to
      be produced by amino acid-based biosynthetic pathways. Our results demonstrate
      that relatively simple cultivation techniques can lead to the isolation of new
      bacterial taxa that are capable of the production of alkaloid secondary
      metabolites with antibacterial activities. These findings support continued
      investment in cultivation techniques as a method for natural product discovery. 

PMID- 26299671
TI  - RNAi-mediated knockdown of the CLN3 gene inhibits proliferation and promotes
      apoptosis in drug-resistant ovarian cancer cells.
AB  - CLN3 is a recently identified anti-apoptotic gene, which has been demonstrated to
      be highly expressed in a diverse range of cancer cell lines, including ovarian
      cancer. In the present study, RNA interference, mediated by a lentivirus
      expressing CLN3 short hairpin RNA (shRNA) was utilized to knockdown the
      expression of CLN3 in the A2780 human ovarian cancer cell line, and its cisplatin
      resistant and carboplatin-resistant sublines, A2780/DDP and A2780/CBP cells. It
      was revealed that the mRNA and protein expression levels of CLN3 were
      significantly reduced in the CLN3-specific shRNA-transduced cells, compared with
      the untransduced and control shRNA-transduced cells. In addition, specific
      knockdown of CLN3 in these cells inhibited cell proliferation and led to cell
      cycle arrest at the G0/G1 phase, with eventual apoptosis. CLN3 knockdown caused
      increases in the levels of Bax, FAX, cleaved-caspase 3, cleaved-caspase 8 and
      cleaved-RARP, but decreased the level of Bcl-2. Finally, it was observed that
      CLN3 depletion markedly reduced the half maximum inhibitory concentration in the
      A2780/DDP and A2780/CBP cells. Taken together, these data suggested that CLN3 is
      involved in tumorigenesis and drug resistance in ovarian cancer, and may serve as
      a promising therapeutic target for its treatment.

PMID- 26299673
TI  - Adaptive Assembly: Maximizing the Potential of a Given Functional Peptide with a
      Tailor-Made Protein Scaffold.
AB  - Protein engineering that exploits known functional peptides holds great promise
      for generating novel functional proteins. Here we propose a combinatorial
      approach, termed adaptive assembly, which provides a tailor-made protein scaffold
      for a given functional peptide. A combinatorial library was designed to create a
      tailor-made scaffold, which was generated from beta hairpins derived from a 10
      residue minimal protein "chignolin" and randomized amino acid sequences. We
      applied adaptive assembly to a peptide with low affinity for the Fc region of
      human immunoglobulin G, generating a 54-residue protein AF.p17 with a 40,600-fold
      enhanced affinity. The crystal structure of AF.p17 complexed with the Fc region
      revealed that the scaffold fixed the active conformation with a unique structure
      composed of a short alpha helix, beta hairpins, and a loop-like structure.
      Adaptive assembly can take full advantage of known peptides as assets for
      generating novel functional proteins. 

PMID- 26299674
TI  - Eosinophil-Mediated Cardiac Injury Possibly Due to Dimethyl Fumarate.

PMID- 26299675
TI  - Scientific output does not preclude regular physical activity in young Polish
      cardiologists.

PMID- 26299676
TI  - Understanding Solidification of Polythiophene Thin Films during Spin-Coating:
      Effects of Spin-Coating Time and Processing Additives.
AB  - Spin-coating has been used extensively in the fabrication of electronic devices;
      however, the effects of the processing parameters have not been fully explored.
      Here, we systematically characterize the effects of the spin-coating time on the
      microstructure evolution during semiconducting polymer solidification in an
      effort to establish the relationship between this parameter and the performances
      of the resulting polymer field-effect transistors (FETs). We found that a short
      spin-coating time of a few seconds dramatically improve the morphology and
      molecular order in a conjugated polymer thin film because the pi-pi stacking
      structures formed by the polymer molecules grow slowly and with a greater degree
      of order due to the residual solvent present in the wet film. The improved
      ordering is correlated with improved charge carrier transport in the FETs
      prepared from these films. We also demonstrated the effects of various processing
      additives on the resulting FET characteristics as well as on the film drying
      behavior during spin-coating. The physical properties of the additives are found
      to affect the film drying process and the resulting device performance. 

PMID- 26299677
TI  - Heart rate and adverse outcomes in patients with atrial fibrillation: A combined
      AFFIRM and AF-CHF substudy.
AB  - BACKGROUND: An elevated resting heart rate has been associated with adverse
      cardiovascular outcomes. Its prognostic value has not specifically been examined
      in patients with atrial fibrillation. OBJECTIVE: The purpose of this study was to
      assess the relationship between resting heart rate measured in sinus rhythm and
      in atrial fibrillation and subsequent hospitalizations and death. METHODS: An
      analysis of individual patient-level data from subjects enrolled in the AFFIRM
      and AF-CHF trials was conducted to determine the impact of resting heart rate on
      hospitalizations and mortality. Separate analyses were performed in atrial
      fibrillation and sinus rhythm. A total of 7159 baseline ECGs (4848 in atrial
      fibrillation, 2311 in sinus rhythm) were analyzed in 5164 patients (34.8% female,
      age 68.2 +/- 8.3 years). RESULTS: During mean follow-up of 40.8 +/- 16.3 months,
      1016 patients died (668 cardiovascular deaths), and 3150 required at least 1
      hospitalization (2215 cardiovascular). An elevated baseline heart rate in sinus
      rhythm was associated with increased all-cause mortality [hazard ratio (HR) 1.24
      per 10 bpm increase, 95% confidence interval (CI) 1.14-1.36, P < .0001]. In
      contrast, a baseline heart rate in atrial fibrillation was not associated with
      mortality. However, compared to heart rates 90-114 bpm in atrial fibrillation, a
      heart rate >114 bpm was independently associated with all-cause (HR 1.18, 95% CI
      1.06-1.31, P = .0018) and cardiovascular (HR 1.25, 95% CI 1.10-1.42, P = .0005)
      hospitalizations. CONCLUSION: In patients with a history of atrial fibrillation,
      an elevated baseline heart rate in sinus rhythm is independently associated with
      mortality. In contrast, the baseline heart rate in atrial fibrillation is not
      associated with mortality but predicts hospitalizations.

PMID- 26299678
TI  - Trajectory and Model Studies of Collisions of Highly Excited Methane with Water
      Using an ab Initio Potential.
AB  - Quasi-classical trajectory studies have been performed for the collision of
      internally excited methane with water using an accurate methane-water potential
      based on a full-dimensional, permutationally invariant analytical representation
      of energies calculated at a high level of theory. The results suggest that most
      energy transfer takes place at impact parameters smaller than about 8 Bohr;
      collisions at higher impact parameters are mostly elastic. Overall, energy
      transfer is fairly facile, with values for ?DeltaEdown? and ?DeltaEup?
      approaching almost 2% of the total excitation energy. A classical model
      previously developed for the collision of internally excited molecules with atoms
      (Houston, P. L.; Conte, R.; Bowman, J. M. J. Phys. Chem. A 2015, 119, 4695-4710)
      has been extended to cover collisions of internally excited molecules with other
      molecules. For high initial rotational levels, the agreement with the trajectory
      results is quite good (R(2) ~ 0.9), whereas for low initial rotational levels it
      is only fair (R(2) ~ 0.7). Both the model and the trajectories can be
      characterized by a four-dimensional joint probability distribution,
      P(J1,f,DeltaE1,J2,f,DeltaE2), where J1,f and J2,f are the final rotational levels
      of molecules 1 and 2 and DeltaE1 and DeltaE2 are the respective changes in
      internal energy. A strong anticorrelation between DeltaE1 and DeltaE2 is observed
      in both the model and trajectory results and can be explained by the model. There
      is evidence in the trajectory results for a small amount of V <-> V energy
      transfer from the water, which has low internal energy, to the methane, which has
      substantial internal energy. This observation suggests that V <-> V energy
      transfer in the other direction also occurs. 

PMID- 26299679
TI  - Insulin resistance and sarcopenia are closely related to metabolic syndrome in
      male and female adolescents.

PMID- 26299681
TI  - Surfactant therapy for bronchiolitis in critically ill infants.
AB  - BACKGROUND: Bronchiolitis is one of the most frequent causes of respiratory
      failure in infants; some infants will require intensive care and mechanical
      ventilation. There is lack of evidence regarding effective treatment for
      bronchiolitis other than supportive care. Abnormalities of surfactant quantity or
      quality (or both) have been observed in severe cases of bronchiolitis. Exogenous
      surfactant administration appears to favourably change the haemodynamics of the
      lungs and may be a potentially promising therapy for severe bronchiolitis. This
      is an update of a review published in Issue 9, 2012. We did not identify any new
      studies for inclusion, and our conclusions remain unchanged. OBJECTIVES: To
      evaluate the efficacy of exogenous surfactant administration (i.e. intratracheal
      administration of surfactant of any type (whether animal-derived or synthetic),
      at any dose and at any time after start of ventilation) compared to placebo, no
      intervention or standard care in reducing mortality and the duration of
      ventilation in infants and children with bronchiolitis requiring mechanical
      ventilation. SEARCH METHODS: We searched the Cochrane Central Register of
      Controlled Studies (CENTRAL; 2015, Issue 5) which contains the Cochrane Acute
      Respiratory Infections Group's Specialised Register; MEDLINE (1948 to June week
      3, 2015); EMBASE (1974 to June 2015); CINAHL (1982 to June 2015); LILACS (1985 to
      June 2015); and Web of Science (1985 to June 2015). SELECTION CRITERIA: We
      considered prospective, randomised controlled trials (RCTs) and quasi-RCTs
      evaluating the effect of exogenous surfactant in infants and children with
      bronchiolitis requiring mechanical ventilation. DATA COLLECTION AND ANALYSIS: Two
      review authors selected studies independently. We extracted the data using a
      predefined proforma, independently analysed the data, and performed meta
      analyses. MAIN RESULTS: We included three small RCTs enrolling 79 participants.
      Two trials did not use a placebo in the control arms and the third trial used air
      placebo. Two included studies reported no mortality. We judged all three of the
      included studies to be at low risk or unclear risk across all risk of bias
      categories; we did not judge any of the studies to be at high risk of bias in any
      category. Our pooled analysis of the three trials revealed that duration of
      mechanical ventilation was not significantly different between the groups (mean
      difference (MD) -63.04, 95% confidence interval (CI) -130.43 to 4.35 hours) but
      duration of intensive care unit (ICU) stay was less in the surfactant group
      compared to the control group: MD -3.31, 95% CI -6.38 to -0.25 days. After
      excluding one trial which produced significant heterogeneity, the duration of
      mechanical ventilation and duration of ICU stay were significantly lower in the
      surfactant group compared to the control group: MD -28.99, 95% CI -40.10 to 
      17.87 hours; and MD -1.81, 95% CI -2.42 to -1.19 days, respectively. Use of
      surfactant had favourable effects on oxygenation and CO2 elimination. No adverse
      effects and no complications were observed in any of the three included studies.
      The level of evidence for duration of mechanical ventilation, duration of
      intensive care unit stay, oxygenation parameters, and carbon dioxide parameters
      was of moderate quality. AUTHORS' CONCLUSIONS: Use of surfactant had favourable
      effects on duration of mechanical ventilation, duration of ICU stay, oxygenation,
      and CO2 elimination. However, the studies are few and small (n = 79) so available
      evidence is insufficient to establish the effectiveness of surfactant therapy for
      bronchiolitis in critically ill infants who require mechanical ventilation. There
      is a need for larger trials with adequate power and a cost-effectiveness analysis
      to evaluate the effectiveness of exogenous surfactant therapy for infants with
      bronchiolitis who require intensive care management.

PMID- 26299682
TI  - Protein Kinase-A Inhibition Is Sufficient to Support Human Neural Stem Cells Self
      Renewal.
AB  - Human pluripotent stem cell-derived neural stem cells offer unprecedented
      opportunities for producing specific types of neurons for several biomedical
      applications. However, to achieve it, protocols of production and amplification
      of human neural stem cells need to be standardized, cost effective, and safe.
      This means that small molecules should progressively replace the use of media
      containing cocktails of protein-based growth factors. Here we have conducted a
      phenotypical screening to identify pathways involved in the regulation of hNSC
      self-renewal. We analyzed 80 small molecules acting as kinase inhibitors and
      identified compounds of the 5-isoquinolinesulfonamide family, described as
      protein kinase A (PKA) and protein kinase G inhibitors, as candidates to support
      hNSC self-renewal. Investigating the mode of action of these compounds, we found
      that modulation of PKA activity was central in controlling the choice between
      self-renewal or terminal neuronal differentiation of hNSC. We finally
      demonstrated that the pharmacological inhibition of PKA using the small molecule
      HA1004 was sufficient to support the full derivation, propagation, and long-term
      maintenance of stable hNSC in absence of any other extrinsic signals. Our results
      indicated that tuning of PKA activity is a core mechanism regulating hNSC self
      renewal and differentiation and delineate the minimal culture media requirement
      to maintain undifferentiated hNSC in vitro.

PMID- 26299683
TI  - Administration of Lactobacillus gasseri SBT2055 suppresses macrophage
      infiltration into adipose tissue in diet-induced obese mice.
AB  - Administration of Lactobacillus gasseri SBT2055 (LG2055) has been shown to
      prevent body weight gain and it also down-regulates the expression of the Ccl2
      gene in adipose tissue in diet-induced obese mice. The CC chemokine ligand 2 has
      a crucial role in macrophage infiltration into adipose tissue, which is known to
      exacerbate inflammation. However, it is not yet known how LG2055 affects the
      invasion of macrophages into adipose tissue. C57BL/6J male mice were fed a normal
      fat diet (10 % energy fat), high-fat diet (HFD; 45 % energy fat), or HFD
      containing LG2055 for 12 weeks. After the feeding period, gene expression and
      macrophage population in adipose tissue were analysed by real-time PCR and flow
      cytometry, respectively. Body weight and abdominal fat weight were not altered by
      feeding LG2055. Flow cytometry analysis revealed that the population of
      macrophages in adipose tissue was significantly reduced by feeding LG2055
      compared with HFD only. Furthermore, the ratio of classically activated
      inflammatory macrophages (M1 macrophages) to total macrophages was significantly
      decreased in the LG2055-fed group. The expressions of Ccl2, Ccr2 and Lep were
      down-regulated and that of Il6, Tnf and Nos2 tended to be down-regulated in
      adipose tissue by feeding LG2055. In addition, fasting glucose levels were
      significantly decreased in the LG2055-fed group. These data suggest that
      administration of LG2055 might attenuate inflammation, which is caused by the
      intake of an HFD, through the inhibition of macrophage invasion into adipose
      tissue. 

PMID- 26299684
TI  - Imaging Internal Structure of Long Bones Using Wave Scattering Theory.
AB  - An ultrasonic wavefield imaging method is developed to reconstruct the internal
      geometric properties of long bones using zero-offset data acquired axially on the
      bone surface. The imaging algorithm based on Born scattering theory is
      implemented with the conjugate gradient iterative method to reconstruct an
      optimal image. In the case of a multilayered velocity model, ray tracing through
      a smooth medium is used to calculate the traveled distance and traveling time.
      The method has been applied to simulated and real data. The results indicate that
      the interfaces of the top cortex are accurately imaged and correspond favorably
      to the original model. The reconstructed bottom cortex below the marrow is less
      accurate mainly because of the low signal-to-noise ratio. The current imaging
      method has successfully recovered the top cortical layer, providing a potential
      tool to investigate the internal structures of long bone cortex for osteoporosis
      assessment. 

PMID- 26299685
TI  - Heel Pad Stiffness in Plantar Heel Pain by Shear Wave Elastography.
AB  - The goal of the study was to evaluate the reliability of supersonic shear wave
      elastography in measuring heel pad stiffness and the change in heel pad stiffness
      in patients with plantar heel pain. In the reliability test involving 12 normal
      participants, each heel pad was tested six times in succession, and adequate
      reliability was reflected in the intraclass correlation coefficients (0.95, 0.93
      and 0.96 for the microchambers, macrochambers and bulk heel pad, respectively).
      In the clinical assessment involving 20 normal participants and 16 unilateral
      plantar heel pain patients, diseased heel pads (86.8 +/- 22.9, 36.8 +/- 7.7 and
      46.6 +/- 10.9 kPa for the microchambers, macrochambers and bulk heel pad,
      respectively) were significantly stiffer than unaffected heel pads (66.8 +/-
      14.1, 25.2 +/- 5.7, 34.2 +/- 6.6 kPa) and those of normal participants (60.9 +/-
      11.4, 26.3 +/- 6.1, 31.8 +/- 6.3 kPa), suggesting that the heel pad with plantar
      heel pain was associated with loss of elasticity. 

PMID- 26299687
TI  - Biweekly gemcitabine therapy induces complete remission in cutaneous angiosarcoma
      resistant to multiple anticancer drugs.

PMID- 26299686
TI  - Non-immune immunoglobulins shield Schistosoma japonicum from host
      immunorecognition.
AB  - Schistosomiasis is a major human parasitic disease with a global impact.
      Schistosoma japonicum, the most difficult to control, can survive within host
      veins for decades. Mechanisms of immune evasion by the parasite, including
      antigenic variation and surface masking, have been implicated but not well
      defined. In this study, we defined the immunoglobulin-binding proteomes of S.
      japonicum using human IgG, IgM, and IgE as the molecular bait for affinity
      purification, followed by protein identification by liquid chromatography with
      tandem mass spectrometry (LC-MS/MS). Several proteins situated at the tegument of
      S. japonicum were able to nonselectively bind to the Fc domain of host
      immunoglobulins, indicating a mechanism for the avoidance of host immune
      attachment and recognition. The profile of the immunoglobulin-binding proteomes
      provides further clues for immune evasion mechanisms adopted by S. japonicum. 

PMID- 26299688
TI  - Mucosal immunology: Living in harmony.

PMID- 26299689
TI  - Stimuli-Responsive Matrix-Assisted Colorimetric Water Indicator of
      Polydiacetylene Nanofibers.
AB  - An alternative signal transduction mechanism of polydiacetylene (PDA) sensors is
      devised by combining stimuli-responsive polymer hydrogel as a matrix and PDA
      sensory materials as a signal-generating component. We hypothesized that
      volumetric expansion of the polymer hydrogel matrix by means of external stimuli
      can impose stress on the imbedded PDA materials, generating a sensory signal. PDA
      assembly as a sensory component was ionically linked with the alginate hydrogel
      in order to transfer the volumetric expansion force of alginate hydrogel
      efficiently to the sensory PDA molecules. Under the same swelling ratio of
      alginate hydrogel, alginate gel having embedded 1-dimensional thin PDA nanofibers
      (~20 nm diameter) presented a sharp color change while 0-dimensional PDA liposome
      did not give any sensory signal when it was integrated in alginate gel. The
      results implied that dimensionality is an important design factor to realize
      stimuli-responsive matrix-driven colorimetric PDA sensory systems; more effective
      contact points between 1-dimensional PDA nanofibers and the alginate matrix much
      more effectively transfer the external stress exerted by the volumetric expansion
      force, and thin PDA nanofibers respond more sensitively to the stress. 

PMID- 26299690
TI  - Spontaneous reduction of ileoileal adult intussusception after blunt abdominal
      injury.
AB  - This is the first case report of an adult who had spontaneous reduction of
      ileoileal intussusception occurred after punching to the abdomen. A 40-year-old
      man was brought to our emergency department by ground ambulance due to pounding
      and punching a few hours ago. Physical examination showed multiple dermabrasions
      on his face, abdomen, and lower extremities. All other examinations were
      unremarkable except that of mild abdominal pain. Laboratory results gave no
      clues. On abdominal x-ray, paucity of intestinal gas, pseudomass and surrounding
      gas appearances were visible. No nausea or vomiting occurred during observation.
      His abdominal pain resolved gradually. On the 24th hour after admission, control
      computed tomography showed that the findings of intussusception disappeared. He
      was discharged after 1 day of observation. Outpatient follow-up did not show any
      abnormality. We suggest that, in patients with mild to moderate trauma, even if
      the patient has mild abdominal pain, physicians should rule out invagination.
      Computed tomography is the suggested imaging modality. These patients should be
      kept in close follow-up. If symptoms resolve and intussusception findings
      disappear in computed tomography, no further treatment is required.

PMID- 26299691
TI  - Time-to-reperfusion in STEMI undergoing interhospital transfer using smartphone
      and WhatsApp messenger.
AB  - OBJECTIVE: The objective of this study is to assess the efficacy of WhatsApp
      application as a communication method among the emergency physician (EP) in a
      rural hospital without percutaneous coronary intervention (PCI) capability and
      the interventional cardiologist at a tertiary PCI center. BACKGROUND: Current
      guidelines recommend that patients with ST-segment elevation myocardial
      infarction (STEMI) receive primary PCI within 90 minutes. This door-to-balloon
      (D2B) time has been difficult to achieve in rural STEMI. METHODS AND RESULTS: We
      evaluated 108 patients with STEMI in a rural hospital with emergency department
      but without PCI capability to determine the impact of WhatsApp triage and
      activation of the cardiac catheterization laboratory on D2B time. The images were
      obtained from cases of suspected STEMI using the smartphones by the EP and were
      sent to the interventional cardiologist via the WhatsApp application (group 1,
      n=53). The control group included concurrently treated patients with STEMI during
      the same period but not receiving triage (group 2, n=55). The D2B time was
      significantly shorter in the intervention group (109+/-31 vs 130+/-46 minutes,
      P<.001) with significant reduction in false STEMI rate as well. CONCLUSION: This
      study demonstrates that use of WhatsApp triage with activation of the cardiac
      catheterization laboratory was associated with shorter D2B time and results in a
      greater proportion of patients achieving guideline recommendations. The method is
      cheap, quick, and easy to operate.

PMID- 26299692
TI  - Successful treatment of flecainide-induced cardiac arrest with extracorporeal
      membrane oxygenation in the ED.
AB  - Flecainide is a class Ic antidysrhythmic agent used to prevent and treat
      tachydysrhythmias. Flecainide toxicity primarily causes cardiovascular and
      neurologic effects through sodium-channel blockade. There is scant evidence to
      support specific management, and recommended therapies have been extrapolated
      from management of other sodium-channel blocking drugs. Traditionally, these
      therapies have consisted of intravenous fluids, sodium bicarbonate, vasopressors,
      and cardiac pacing. Novel therapies include intravenous fat emulsion and
      venoarterial extracorporeal membrane oxygenation (VA-ECMO). A 24-year-old woman
      ingested her husband's flecainide and presented to the emergency department (ED)
      in profound shock with a wide complex bradydysrhythmia. Despite aggressive
      medical therapy including sodium bicarbonate, vasopressors, cardiac pacing, and
      intravenous fat emulsion, her condition deteriorated and she developed pulseless
      electrical activity (PEA) cardiac arrest refractory to standard resuscitation.
      Venoarterial extracorporeal membrane oxygenation was initiated in the ED, and the
      patient remained comatose and critically ill in the intensive care unit. Her
      hemodynamics and mental status recovered, but she had compartment syndrome in her
      left leg requiring fasciotomy. She was discontinued from VA-ECMO on hospital day
      5, extubated on hospital day 6, and discharged home with excellent neurologic
      recovery on hospital day 19. Intravenous fat emulsion is thought to sequester the
      offending agent in a plasma lipid "sink," alter ion channel permeability, and/or
      modify fatty acid utilization by the myocardium. The quality of evidence for
      intravenous fat emulsion is generally low. Venoarterial extracorporeal membrane
      oxygenation was used in this patient to restore organ perfusion and allow
      intrinsic drug metabolism and elimination. Venoarterial extracorporeal membrane
      oxygenation should be strongly considered for refractory shock and/or cardiac
      arrest secondary to flecainide toxicity.

PMID- 26299694
TI  - Infarction of the choroid plexus in basilar artery occlusion.

PMID- 26299693
TI  - Analysis of human soft palate morphogenesis supports regional regulation of
      palatal fusion.
AB  - It is essential to complete palate closure at the correct time during fetal
      development, otherwise a serious malformation, cleft palate, will ensue. The
      steps in palate formation in humans take place between the 7th and 12th week and
      consist of outgrowth of palatal shelves from the paired maxillary prominences,
      reorientation of the shelves from vertical to horizontal, apposition of the
      medial surfaces, formation of a bilayered seam, degradation of the seam and
      bridging of mesenchyme. However, in the soft palate, the mechanism of closure is
      unclear. In previous studies it is possible to find support for both fusion and
      the alternative mechanism of merging. Here we densely sample the late embryonic
      early fetal period between 54 and 74 days post-conception to determine the timing
      and mechanism of soft palate closure. We found the epithelial seam extends
      throughout the soft palates of 57-day specimens. Cytokeratin antibody staining
      detected the medial edge epithelium and distinguished clearly that cells in the
      midline retained their epithelial character. Compared with the hard palate, the
      epithelium is more rapidly degraded in the soft palate and only persists in the
      most posterior regions at 64 days. Our results are consistent with the soft
      palate following a developmentally more rapid program of fusion than the hard
      palate. Importantly, the two regions of the palate appear to be independently
      regulated and have their own internal clocks regulating the timing of seam
      removal. Considering data from human genetic and mouse studies, distinct anterior
      posterior signaling mechanisms are likely to be at play in the human fetal
      palate.

PMID- 26299695
TI  - Decisions, Science, and Values: Crafting Regulatory Alternatives Analysis.
AB  - Emerging "prevention-based" approaches to chemical regulation seek to minimize
      the use of toxic chemicals by mandating or directly incentivizing the adoption of
      viable safer alternative chemicals or processes. California and Maine are
      beginning to implement such programs, requiring manufacturers of consumer
      products containing certain chemicals of concern to identify and evaluate
      potential safer alternatives. In the European Union, the REACH program imposes
      similar obligations on manufacturers of certain substances of very high concern.
      Effective prevention-based regulation requires regulatory alternatives analysis
      (RAA), a methodology for comparing and evaluating the regulated chemical or
      process and its alternatives across a range of relevant criteria. RAA has both
      public and private dimensions. To a significant degree, alternatives analysis is
      an aspect of product design; that is, the process by which private industry
      designs the goods it sells. Accordingly, an RAA method should reflect the
      attributes of well-crafted product design tools used by businesses. But RAA adds
      health and environmental objectives to the mix of concerns taken into account by
      the product designer. Moreover, as part of a prevention-based regulatory regime,
      it implicates important public values such as legitimacy, equity, public
      engagement, and accountability. Thus, an RAA should reflect both private
      standards and public values, and be evaluated against them. This article adopts
      that perspective, identifying an integrated set of design principles for RAA, and
      illustrating the application of those principles. 

PMID- 26299696
TI  - In Vivo Characterization of Retinal Microvascular Network in Multiple Sclerosis.

PMID- 26299697
TI  - Familial Exudative Vitreoretinopathy: Spectral-Domain Optical Coherence
      Tomography of the Vitreoretinal Interface, Retina, and Choroid.
AB  - PURPOSE: The in vivo microstructural features of familial exudative
      vitreoretinopathy (FEVR) have not been well described. We present new anatomic
      features of FEVR with functional and genetic correlations. DESIGN: Consecutive,
      retrospective, observational case series. PARTICIPANTS: Patients with FEVR
      treated from 2009 to 2014. METHODS: We identified 346 patients with FEVR. Those
      imaged with spectral-domain optical coherence tomography (SD OCT) with or without
      enhanced depth imaging (EDI) were included, and images were correlated with best
      corrected visual acuity (BCVA), widefield angiography, fundus autofluorescence
      (AF), and wnt signaling pathway mutations. MAIN OUTCOME MEASURES: Exploratory SD
      OCT findings and BCVA. RESULTS: A total of 225 imaging sessions were acquired in
      74 eyes from 41 patients. Mean age was 19.0 years. Sixty-seven eyes (91%) had
      interpretable images, of which 50 (75%) had anomalous microstructural findings;
      all eyes with FEVR severity of stage 2 or greater had abnormalities. A broad
      spectrum of features were identified: various forms of posterior hyaloidal
      organization, vitreomacular traction (VMT), vitreopapillary traction, vitreo-fold
      traction, vitreo-laser scar adhesion, diminished foveal contour, persistent fetal
      foveal architecture, cystoid macular edema (CME), intraretinal exudates and
      subretinal lipid aggregation, dry or edematous radial folds, and disruption of
      the ellipsoid zone. Mean foveal, central macular, and choroidal thicknesses were
      305+/-145 MUm, 337+/-160 MUm, and 216+/-64 MUm, respectively. In stages 1 to 2,
      greater foveal and central macular thicknesses (Rho=0.493, 0.544, respectively;
      both P<0.001) correlated with poorer BCVA, but not choroidal thickness
      (Rho=0.032; P=0.868). Posterior hyaloidal organization (P<0.001), VMT (P<0.001),
      CME (P<0.001), exudation (P<0.001), and disruption of the ellipsoid zone
      (P<0.001) were associated with poorer BCVA. Disruption of the ellipsoid zone
      (beta=0.699; P<0.001) and posterior hyaloidal organization (beta=0.289; P=0.011)
      retained significance in multivariate modeling (R2=0.627; P<0.001). Spectral
      domain OCT detected all cases of angiographic edema and areas of outer retinal
      dysfunction that were hypoautofluorescent on AF. Microstructural-genetic
      associations were not identified. CONCLUSIONS: Spectral-domain OCT imaging
      identified microstructural anomalies in the majority of patients with FEVR.

PMID- 26299698
TI  - The Prevalence of Coworker Conflict Including Bullying in a Unionized U.S. Public
      Sector Workforce.
AB  - Workplace violence is an enormous problem worldwide; incidents where the
      perpetrator is a current or former employee are an important dimension. This
      large cross-sectional survey examined the prevalence of this problem among a U.S.
      state government unionized public sector workforce. Using participatory action
      research methods, we conducted a web-based survey of members of that workforce
      from a single northeast U.S. state, receiving 11,874 completed surveys (response
      rate: 71.8%). Overall, 10.0% of the respondents indicated that they had been
      bullied at work during the prior 6 months, with 71.9% of those who reported
      regular bullying identifying the perpetrator as a supervisor and/or top
      management. The prevalence of bullying was similar to the rates reported in
      Europe and Scandinavia (5%-30%). Those reports also identified the person(s)
      responsible for the behavior as being predominantly of higher status within the
      organization. 

PMID- 26299699
TI  - Determination of the Relationship Between rs4986790 and rs4986791 Variants of
      TLR4 Gene and Lung Cancer.
AB  - Chronic inflammation triggers DNA damage and oncogenic mutations and causes tumor
      formation and tumor progression. One of the important components of the
      inflammatory response is Toll-like receptor (TLR) family. The objective of our
      study is to determine the relationship between rs4986790(+896A/G) and
      rs4986791(+1196C/T) gene polymorphisms and lung cancer risk. PCR-RFLP technique
      was carried out to identify the genotypes in 100 control individuals and 160 lung
      cancer patients. DNA extracted from peripheral blood samples were amplified and
      digested with NcoI and HinfI then visualized. We did not find any difference
      between genotype frequencies between controls and patients (p > 0.05) in
      rs4986790. But a significant difference between control group and patients with
      lung cancer as for genotype frequencies (chi (2) = 4.19, p = 0.041) in rs4986791
      variants was found. Our data indicate that any correlation was not found between
      rs4986790 polymorphism and lung cancer, while a correlation between rs4986791 and
      lung cancer has been determined and found to be associated with lung cancer risk.

PMID- 26299700
TI  - Use of a blog in an undergraduate nursing leadership course.
AB  - In this study, the use of a blog in a senior leadership clinical nursing course
      was analyzed qualitatively through two means; focus group interviews of those
      using the blog, and analysis of blog content. Initial feelings expressed by
      students were annoyance and intimidation concerning the blogging assignment.
      These feelings quickly dissipated, with students verbalizing many positive
      aspects related to the blog, including having a place to reflect, feeling
      connected as a group, valuing feedback provided by their peers, and learning from
      theirs and others' experiences. The mechanics of having to synthesize their
      thoughts in written form, in a shared venue was also identified by students to be
      helpful for their learning. Blog posts were primarily related to student
      experiences, with students identifying a "lesson learned" in most posts. Student
      comments were geared to providing support of fellow students, through words of
      encouragement or through sharing similar experiences. Instructors felt the blog,
      in addition to helping students to synthesize their thoughts, helped to monitor
      how students were learning and progressing throughout the semester, and helped
      them to transition from nursing student to practicing professional. The
      researchers concluded that blogging in a senior leadership clinical nursing
      course promotes reflection is an effective way to enhance student learning. 

PMID- 26299701
TI  - Written debriefing: Evaluating the impact of the addition of a written component
      when debriefing simulations.
AB  - Debriefing, the reflective period following a simulation, is said to be where the
      bulk of simulation learning takes place. Many expert opinions regarding
      debriefing exist, but evidence-based best practices have yet to be identified.
      Written debriefing is one of these practices; experts state learning can be
      extended through the addition of a written component to the debriefing process,
      but no evidence exists to support this. This study compares three debriefing
      types: discussion alone, and discussion followed by journaling or blogging.
      Undergraduate nursing students participating in a simulation were randomized as a
      simulation group to one of these three debriefing types. Following completion of
      debriefing activities, students completed a Debriefing Experience Scale, a tool
      designed to evaluate the student experience during debriefing. Data obtained from
      completed scales were analyzed with ANOVA followed by Fisher LSD post hoc
      testing. The results showed the students preferred their experience with
      discussion debriefing over discussion debriefing with a written component added. 

PMID- 26299702
TI  - Ultrasound cavitation versus cryolipolysis for non-invasive body contouring.
AB  - BACKGROUND/OBJECTIVES: The demand for non-surgical and non-invasive devices is
      continuous and increasing. Such devices have gradually gained ground in the
      reduction of localised fat and the improvement of body contouring. The study
      aimed to compare the effects of ultrasound cavitation and cryolipolysis on
      localised abdominal fat. METHODS: In total, 60 participants with a body mass
      index (BMI) over 30 kg/m2 , whose age ranged between 25 and 45 years, were
      included. The participants were randomly assigned to three groups of 20 each,
      using ultrasound cavitation and diet, cryolipolysis and diet, and diet only (the
      control group), respectively. Measures were bodyweight, BMI, waist circumference
      and suprailiac skinfold were measured at the beginning of the study and 2 months
      later. RESULTS: The three groups showed significant improvements in all measured
      variables after 2 months. There was no statistically significant difference in
      bodyweight or in BMI among the groups after treatment. However, the groups using
      ultrasound cavitation and cryolipolysis showed better post-treatment improvement
      than the diet-only group in waist circumference and suprailiac skinfold. There
      was no statistically significant difference post-treatment between the cavitation
      and cryolipolysis groups in waist circumference or suprailiac skinfold.
      CONCLUSION: Both ultrasound cavitation and cryolipolysis are safe and effective
      for the reduction of abdominal fat thickness and for abdominal contouring.

PMID- 26299703
TI  - microRNA profiling for early detection of nonmelanoma skin cancer.
AB  - BACKGROUND: microRNAs (miRNAs) are single-stranded, noncoding RNA molecules.
      Given the vast regulatory potential of miRNAs and their often tissue-specific and
      disease-specific expression patterns, miRNAs are being assessed as possible
      biomarkers to aid diagnosis and prediction of different types and stages of
      cancers, including skin cancer. Basal cell carcinoma (BCC) and squamous cell
      carcinoma (SCC) are the most common forms of nonmelanoma skin cancer (NMSC). BCC
      originates from the basal layer of the epidermis, while SCC arises from epidermal
      keratinocytes or from the dermal appendages. Although NMSCs are currently the
      most common types of malignancies, both BCC and SCC have a better than 95% cure
      rate if detected early. AIM: To identify plasma miRNAs suitable for early
      detection of NMSC. METHODS: Expression profiles of 741 miRNAs were evaluated
      using high-throughput real-time quantitative PCR from plasma samples in 42
      patients with NMSC and 282 healthy controls (HCs). RESULTS: Our results
      demonstrated that in patients with NMSC, compared with HCs, expression levels of
      miR-30e-3p, miR-145-5p, miR-186-5p and miR-875-5p were significantly (P < 0.05)
      upregulated, while those of miR-19a-3p, miR-25-3p, miR-30a-5p, miR-451 and miR
      576-3p were significantly downregulated. CONCLUSION: Our study suggests that the
      miRNAs with significant changes in expression (miR-19a-3p, miR-25-3p, miR-30a-5p,
      miR-145-5p and miR-186-5p) could serve as novel noninvasive biomarkers for
      detection of NMSC.

PMID- 26299704
TI  - Effects of dietary nucleotides on growth, non-specific immune response and
      disease resistance of sea cucumber Apostichopus japonicas.
AB  - A 9-week feeding trial was conducted to investigate the effects of dietary
      nucleotides (NT) on growth, immune response and disease resistance of sea
      cucumber Apostichopus japonicas (initial weight: 5.87 +/- 0.03 g). Four graded
      levels of dietary NT were designed as 0, 150, 375 and 700 mg/kg, respectively.
      After the feeding trial, sea cucumbers were challenged with Vibrio splendidus for
      the determination of disease resistance. The results showed that the specific
      growth rates were significantly higher in sea cucumber fed the diet with 375
      mg/kg NT than those fed the basal diet without NT supplementation (P < 0.05). The
      highest total coelomocytes counts in coelomic fluid were found in the treatment
      with 150 mg/kg of dietary NT (P < 0.05). Compared to those fed with the basal
      diet, sea cucumber fed diets with nucleotides (>= 375 mg/kg) had significantly
      higher phagocytic activities in coelomic fluid (P < 0.05). Respiratory burst
      activities in coelomic fluid significantly increased with increasing dietary NT
      supplementations up to 700 mg/kg (P < 0.05). No significant differences in the
      activities of superoxide dismutase, total nitric oxide synthase and acid
      phosphatase in coelomic fluid were found among all the treatments (P > 0.05).
      After being challenged with V. splendidus, the cumulative mortalities of sea
      cucumber fed diets with 150 and 375 mg/kg NT were significantly lower than that
      in the treatment without dietary nucleotide supplementation (P < 0.05). Under the
      experimental conditions, the present results confirmed that a diet supplemented
      with 375 mg/kg NT is able to enhance both non-specific immune response and growth
      of sea cucumber in vivo. In conclusion, it was showed that dietary NT does
      increase the growth performance, non-specific immunity and disease resistance of
      sea cucumber. The optimum dietary NT supplementation level for sea cucumber was
      found to be 375 mg/kg. The application of dietary NT may present a novel strategy
      for health management in sea cucumber's aquaculture.

PMID- 26299705
TI  - Prion protein-deficient mice exhibit decreased CD4 T and LTi cell numbers and
      impaired spleen structure.
AB  - The cellular prion protein is expressed in almost all tissues, including the
      central nervous system and lymphoid tissues. To investigate the effects of the
      prion protein in lymphoid cells and spleen structure formation, we used prion
      protein-deficient (Prnp(0/0)) Zurich I mice generated by inactivation of the Prnp
      gene. Prnp(0/0) mice had decreased lymphocytes, in particular, CD4 T cells and
      lymphoid tissue inducer (LTi) cells. Decreased CD4 T cells resulted from impaired
      expression of CCL19 and CCL21 in the spleen rather than altered chemokine
      receptor CCR7 expression. Importantly, some of the white pulp regions in spleens
      from Prnp(0/0) mice displayed impaired T zone structure as a result of decreased
      LTi cell numbers and altered expression of the lymphoid tissue-organizing genes
      lymphotoxin-alpha and CXCR5, although expression of the lymphatic marker
      podoplanin and CXCL13 by stromal cells was not affected. In addition, CD3(
      )CD4(+)IL-7Ralpha(+) LTi cells were rarely detected in impaired white pulp in
      spleens of these mice. These data suggest that the prion protein is required to
      form the splenic white pulp structure and for development of normal levels of CD4
      T and LTi cells.

PMID- 26299706
TI  - Nodal centrality of functional network in the differentiation of schizophrenia.
AB  - A disturbance in the integration of information during mental processing has been
      implicated in schizophrenia, possibly due to faulty communication within and
      between brain regions. Graph theoretic measures allow quantification of
      functional brain networks. Functional networks are derived from correlations
      between time courses of brain regions. Group differences between SZ and control
      groups have been reported for functional network properties, but the potential of
      such measures to classify individual cases has been little explored. We tested
      whether the network measure of betweenness centrality could classify persons with
      schizophrenia and normal controls. Functional networks were constructed for 19
      schizophrenic patients and 29 non-psychiatric controls based on resting state
      functional MRI scans. The betweenness centrality of each node, or fraction of
      shortest-paths that pass through it, was calculated in order to characterize the
      centrality of the different regions. The nodes with high betweenness centrality
      agreed well with hub nodes reported in previous studies of structural and
      functional networks. Using a linear support vector machine algorithm, the
      schizophrenia group was differentiated from non-psychiatric controls using the
      ten nodes with the highest betweenness centrality. The classification accuracy
      was around 80%, and stable against connectivity thresholding. Better performance
      was achieved when using the ranks as feature space as opposed to the actual
      values of betweenness centrality. Overall, our findings suggest that changes in
      functional hubs are associated with schizophrenia, reflecting a variation of the
      underlying functional network and neuronal communications. In addition, a
      specific network property, betweenness centrality, can classify persons with SZ
      with a high level of accuracy. 

PMID- 26299708
TI  - Optimization of proteins and minerals removal from shrimp shells to produce
      highly acetylated chitin.
AB  - Chitin and derivatives used for biomedical or pharmaceutical applications require
      a high level of purity and quality that are difficult to achieve. In this study,
      we propose to optimize the extraction of chitin in order to obtain pure product
      keeping a structure as close as possible to the native form. Thus,
      demineralization step was firstly optimized using response surface methodology.
      In the optimized conditions predicted by the model, the obtained chitin has an
      acetylation degree (DA) and a demineralization degree (DM) equal to 99% and 100%,
      respectively. Then, different microbial and fish crude alkaline proteases were
      tested for their efficiency in deproteinization. Crude alkaline proteases giving
      the highest deproteinization degrees (DP), Bacillus mojavensis A21 and Scorpaena
      scrofa, were selected for chitin extraction. The obtained DP was 88+/-2% and 83+/
      1%, respectively. At the end, effect of the use of mixed enzymatic treatment with
      the two selected crude enzymes and the order of demineralization/deproteinization
      steps were tested. The results demonstrated that two separated steps in enzymatic
      treatments realized on demineralized sample give the best DP (96%) preserving the
      DA (99%). 

PMID- 26299707
TI  - Memory systems in schizophrenia: Modularity is preserved but deficits are
      generalized.
AB  - OBJECTIVE: Schizophrenia patients exhibit impaired working and episodic memory,
      but this may represent generalized impairment across memory modalities or
      performance deficits restricted to particular memory systems in subgroups of
      patients. Furthermore, it is unclear whether deficits are unique from those
      associated with other disorders. METHOD: Healthy controls (n=1101) and patients
      with schizophrenia (n=58), bipolar disorder (n=49) and attention-deficit
      hyperactivity-disorder (n=46) performed 18 tasks addressing primarily verbal and
      spatial episodic and working memory. Effect sizes for group contrasts were
      compared across tasks and the consistency of subjects' distributional positions
      across memory domains was measured. RESULTS: Schizophrenia patients performed
      poorly relative to the other groups on every test. While low to moderate
      correlation was found between memory domains (r=.320), supporting modularity of
      these systems, there was limited agreement between measures regarding each
      individual's task performance (ICC=.292) and in identifying those individuals
      falling into the lowest quintile (kappa=0.259). A general ability factor
      accounted for nearly all of the group differences in performance and agreement
      across measures in classifying low performers. CONCLUSIONS: Pathophysiological
      processes involved in schizophrenia appear to act primarily on general abilities
      required in all tasks rather than on specific abilities within different memory
      domains and modalities. These effects represent a general shift in the overall
      distribution of general ability (i.e., each case functioning at a lower level
      than they would have if not for the illness), rather than presence of a generally
      low-performing subgroup of patients. There is little evidence that memory
      impairments in schizophrenia are shared with bipolar disorder and ADHD.

PMID- 26299709
TI  - Sumatriptan succinate loaded chitosan solid lipid nanoparticles for enhanced anti
      migraine potential.
AB  - The objective of the present investigation was to prepare chitosan solid lipid
      nanoparticles (SLN), containing sumatriptan succinate using solvent injection
      method and to optimize the formulations for brain targeting potential. The
      formulation optimization was performed using three factor two level full
      factorial design so as to minimize the particle size and zeta potential, maximize
      the entrapment efficiency as well as maximize the concentration of drug in brain
      with maximized brain/plasma ratio of the drug. The particle size, zeta potential
      and entrapment efficiency for all the batches were in the range of 192-301.4nm,
      30.2-51.4mV and 76.3-91.1% respectively. The optimized formulation showed a 4.54
      fold increase in brain/blood ratio of drug after 2h of drug administration in
      male Wistar rats. The optimized nanoparticles were characterized by FT-IR
      spectroscopy, DSC, TGA, powder X-ray diffraction study and TEM analysis. It could
      be elucidated from the experimental in vivo and behavioral studies that the
      formulations successfully crossed the blood brain barrier and significantly
      exhibited its anti-migraine activity. Present investigation indicated that the
      hydrophilic drug sumatriptan succinate, loaded in chitosan SLN, can be
      successfully targeted to brain via oral delivery and thus present an effective
      approach for the therapeutic management of migraine. 

PMID- 26299710
TI  - Improved thermal stability of polylactic acid (PLA) composite film via PLA-beta
      cyclodextrin-inclusion complex systems.
AB  - The effects of the incorporation of PLA-beta-cyclodextrin-inclusion complex (IC)
      and beta-cyclodextrin (beta-CD) on biopolyester PLA films were investigated.
      Thermal stability, surface morphology, barrier, and mechanical properties of the
      films were measured at varying IC (1, 3, 5, and 7%) and beta-CD (1 and 5%)
      concentrations. The PLA-IC-composite films (IC-PLA-CFs) showed uniform
      morphological structure, while samples containing beta-CD (beta-CD-PLA-CFs)
      showed high agglomeration of beta-CD due to poor interfacial interaction between
      beta-CD and PLA moieties. According to the thermal property analysis, the 5% IC
      PLA-CFs showed 6.6 times lower dimensional changes (6.5%) at the temperature
      range of 20-80 degrees C than that of pure PLA film (43.0%). The increase of IC
      or beta-CD content in the PLA-composite films shifted the glass transition and
      crystallization temperature to higher temperature regions. The crystallinity of
      both composite films improved by increasing IC or beta-CD content. Both composite
      films had higher oxygen and water vapor permeability as IC or beta-CD content
      increased in comparison to pure PLA film. All the composite films had less
      flexibility and lower tensile strength than the pure PLA film. In conclusion,
      this study shows that the IC technique is valuable to improve the thermal
      expansion stability of PLA-based films. 

PMID- 26299711
TI  - New photocatalyst based on graphene oxide/chitin for degradation of dyes under
      sunlight.
AB  - Sunlight photocatalyst was fabricated by in situ synthesis of Cu2O in the
      regenerated chitin (RC)/graphene oxide (GO) composite film, where the porous
      chitin film was used as the microreactor for the formation of nano Cu2O. Nano
      Cu2O was immobilized and evenly distributed in the matrix and Cu2O tended to grow
      on the GO sheets. Cu2O inside the matrix excite and generate free photoelectrons
      and electron holes, which was responsible for the degradation of dyes, while GO
      transferred the yielded photoelectrons to prevent the generation of local high
      potential zone and induce the chain degradation at more points. So it was found
      that the porous chitin film could load Cu2O and graphene at the same time,
      controlling the size of Cu2O and leading to easy recycle and reuse of the
      photocatalyst. Moreover, the introduction of GO has dramatically improved the
      photocatalytic activity of Cu2O in the Cu2O/GO/RC film, showing great potential
      application in wastewater treatment utilizing solar energy. 

PMID- 26299712
TI  - High concentrations of uric acid inhibit angiogenesis via regulation of the
      Kruppel-like factor 2-vascular endothelial growth factor-A axis by miR-92a.
AB  - BACKGROUND: Angiogenesis is a critical component of many pathological conditions,
      and microRNAs (miRNAs) are indispensable in angiogenesis. It is unclear whether
      miRNAs regulate angiogenesis in the presence of high concentrations of uric acid
      (HUA), and the underlying mechanisms remain unknown. METHODS AND RESULTS: It was
      found that HUA inhibited the angiogenic ability of endothelial cells. miRNA
      expression profiling was conducted using microarray assays in HUA-stimulated
      endothelial cells. Eighteen differentially expressed miRNAs were subjected to
      bioinformatic analyses. The results indicated that miR-92a was negatively
      regulated and was closely related to angiogenesis. Furthermore, the effects of
      miR-92a on HUA-stimulated endothelial cell angiogenesis and the underlying
      mechanisms were investigated in dual-luciferase reporter assays, electrophoretic
      mobility shift assays, immunoblot assays, and tube formation assays. It was
      determined that Kruppel-like factor 2 (KLF2) is a target gene of miR-92a, and
      KLF2 binds the vascular endothelial growth factor-A (VEGFA) promoter to inhibit
      its expression. miR-92a and VEGFA overexpression or KLF2 downregulation
      alleviates the HUA-mediated inhibition of angiogenesis in endothelial cells in
      vitro. CONCLUSIONS: This study reported that there is a novel pathway regulating
      angiogenesis under HUA conditions. In the presence of HUA, miR-92a downregulation
      increased KLF2 expression, subsequently inhibiting VEGFA, which resulted in
      decreased angiogenesis. Thus, this study reports a possible mechanism for
      cardiovascular injury caused by hyperuricemia and suggests that the miR-92a-KLF2
      VEGFA axis may be a target for hyperuricemia treatment.

PMID- 26299713
TI  - Determinants of consumer food waste behaviour: Two routes to food waste.
AB  - Approximately one quarter of the food supplied for human consumption is wasted
      across the food supply chain. In the high income countries, the food waste
      generated at the household level represents about half of the total food waste,
      making this level one of the biggest contributors to food waste. Yet, there is
      still little evidence regarding the determinants of consumers' food waste
      behaviour. The present study examines the effect of psycho-social factors, food
      related routines, household perceived capabilities and socio-demographic
      characteristics on self-reported food waste. Survey data gathered among 1062
      Danish respondents measured consumers' intentions not to waste food, planning,
      shopping and reuse of leftovers routines, perceived capability to deal with
      household food-related activities, injunctive and moral norms, attitudes towards
      food waste, and perceived behavioural control. Results show that perceived
      behavioural control and routines related to shopping and reuse of leftovers are
      the main drivers of food waste, while planning routines contribute indirectly. In
      turn, the routines are related to consumers' perceived capabilities to deal with
      household related activities. With regard to intentional processes, injunctive
      norms and attitudes towards food waste have an impact while moral norms and
      perceived behavioural control make no significant contribution. Implications of
      the study for initiatives aimed at changing consumers' food waste behaviour are
      discussed. 

PMID- 26299714
TI  - Intergenerational differences in beliefs about healthy eating among carers of
      left-behind children in rural China: A qualitative study.
AB  - China's internal migration has left 61 million rural children living apart from
      parents and usually being cared for by grandparents. This study aims to explore
      caregivers' beliefs about healthy eating for left-behind children (LBC) in rural
      China. Twenty-six children aged 6-12 (21 LBC and 5 non-LBC) and 32 caregivers (21
      grandparents, 9 mothers, and 2 uncles/aunts) were recruited in one township in
      rural China. Children were encouraged to keep food diaries followed by in-depth
      interviews with caregivers. Distinct intergenerational differences in beliefs
      about healthy eating emerged: the grandparent generation was concerned about not
      having enough food and tended to emphasise the importance of starchy foods for
      children's growth, due to their past experiences during the Great Famine. On the
      other hand, the parent generation was concerned about food safety and paid more
      attention to protein-source foods including meat, eggs and milk. Parents appeared
      to offer children high-energy food, which was viewed as a sign of economic
      status, rather than as part of a balanced diet. Lack of remittances from migrant
      parents may compromise LBC's food choices. These findings suggest the potential
      for LBC left in the care of grandparents, especially with experience of the Great
      Famine, may be at greater risk of malnutrition than children cared for by
      parents. By gaining an in-depth understanding of intergenerational differences in
      healthy eating beliefs for children, our findings could inform for the
      development of nutrition-related policies and interventions for LBC in rural
      China. 

PMID- 26299715
TI  - A systematic review of longer-term dietary interventions on human cognitive
      function: Emerging patterns and future directions.
AB  - Cognitive function may be affected by long-term diet and most of the support for
      this idea is derived from human correlational studies and animal prescribed diet
      studies. To date there has been no systematic examination of human experimental
      studies that examine whether a prescribed long-term (24 h+) diet can cause
      changes in cognitive function. Here, we review the experimental evidence of long
      term changes in cognition following prescribed diet interventions. A total of 30
      diet interventions were identified and reviewed. Measures of working memory, long
      term memory, and attention appeared most sensitive to dietary manipulation, but
      there was considerable variability in outcome. Additionally, energy and fat
      intake manipulations tended to influence performance on these measures to the
      greatest degree. This review also serves to identify factors that should be
      considered in designing future diet-cognition studies. We also suggest a series
      of cognitive tests based on this review and indicate potentially profitable
      directions to take the diet-cognition literature.

PMID- 26299716
TI  - Multidisciplinary management of colorectal adenocarcinoma associated with anal
      fistula: an Indian series.
AB  - AIM: Adenocarcinomas associated with anal fistula are rare and often present at
      an advanced stage. They are often mistaken for commonly occurring benign
      diseases, leading to delayed diagnosis. Previous reports have predicted inferior
      oncological outcomes for these cases compared with sporadic rectal cancers. We
      are presenting our series of patients with colorectal adenocarcinoma associated
      with anal fistula who were treated with multimodality therapy at a tertiary
      cancer centre in India. METHOD: This was a retrospective review of a
      prospectively maintained database of patients treated at our centre between 1
      July 2013 and 31 March 2015. Of the 15 patients included in the study, 11 had
      prior intervention in the form of seton placement or fistulotomy. Fourteen
      patients had circumferential resection margin (CRM) involvement at initial workup
      and hence were given neoadjuvant chemoradiotherapy (NACRT). None of the patients
      had distant metastasis and only 15% had regional nodal involvement. RESULTS: All
      13 patients included in the final analysis underwent abdominoperineal excision
      (APE). Ten patients (73%) underwent extralevator APE. Plastic reconstruction in
      the form of a V-Y advancement flap for perineal closure was required in six
      patients (46%). On histopathological examination, a mucinous component was found
      to be present in 11 patients (73%). The quality of total mesorectal excision was
      complete in 92% patients. The CRM was free in 92% of patients. Median overall
      survival and disease-free survival were not reached. CONCLUSION: Colorectal
      adenocarcinomas associated with fistula are locally aggressive malignancies with
      a low incidence of lymph node involvement and distant metastasis. NACRT, wider
      resection in the form of extralevator APE, and liberal use of plastic
      reconstruction may result in favourable outcomes.

PMID- 26299717
TI  - Silica promotes the transdifferentiation of rat circulating fibrocytes in vitro.
AB  - To investigate the effects of silica on circulating fibrocytes (cFbs), the
      present study established a primary culture model of rat alveolar macrophages and
      cFbs in vitro. Macrophages were treated with free silica, and their supernatant
      was used to stimulate cFbs. The mRNA expression levels of collagen I, collagen
      III and alpha-smooth muscle actin (SMA) in cFbs were analyzed by reverse
      transcription-quantitative polymerase chain reaction. The intracellular and
      extracellular protein expression levels of collagen I, collagen III and alpha-SMA
      were detected by ELISA and immunofluorescence staining. The results indicated
      that in the cell model, the free silica effectively increased the protein and
      mRNA expression levels of collagen-I, collagen-III and alpha-SMA. The free silica
      significantly promoted the transdifferentiation of cFbs into myofibroblasts in a
      dose-and time-dependent manner.

PMID- 26299718
TI  - Anti-Vascular Endothelial Growth Factor Injections and Intraocular Pressure
      Measurement: Should We Throw the Baby out with the Bath Water?

PMID- 26299719
TI  - Boston Keratoprosthesis with Severe Ecstasia.

PMID- 26299720
TI  - MIGS and the FDA: What's in a Name?

PMID- 26299721
TI  - Pupillary Responses to High-Irradiance Blue Light Correlate with Glaucoma
      Severity.
AB  - PURPOSE: To evaluate whether a chromatic pupillometry test can be used to detect
      impaired function of intrinsically photosensitive retinal ganglion cells (ipRGCs)
      in patients with primary open-angle glaucoma (POAG) and to determine if pupillary
      responses correlate with optic nerve damage and visual loss. DESIGN: Cross
      sectional study. PARTICIPANTS: One hundred sixty-one healthy controls recruited
      from a community polyclinic (55 men; 151 ethnic Chinese) and 40 POAG patients
      recruited from a glaucoma clinic (22 men; 35 ethnic Chinese) 50 years of age or
      older. METHODS: Subjects underwent monocular exposure to narrowband blue light
      (469 nm) or red light (631 nm) using a modified Ganzfeld dome. Each light
      stimulus was increased gradually over 2 minutes to activate sequentially the
      rods, cones, and ipRGCs that mediate the pupillary light reflex. Pupil diameter
      was recorded using an infrared pupillography system. MAIN OUTCOME MEASURES:
      Pupillary responses to blue light and red light were compared between control
      subjects and those with POAG by constructing dose-response curves across a wide
      range of corneal irradiances (7-14 log photons/cm(2) per second). In patients
      with POAG, pupillary responses were evaluated relative to standard automated
      perimetry testing (Humphrey Visual Field [HVF]; Carl Zeiss Meditec, Dublin, CA)
      and scanning laser ophthalmoscopy parameters (Heidelberg Retinal Tomography
      [HRT]; Heidelberg Engineering, Heidelberg, Germany). RESULTS: The pupillary light
      reflex was reduced in patients with POAG only at higher irradiance levels,
      corresponding to the range of activation of ipRGCs. Pupillary responses to high
      irradiance blue light associated more strongly with disease severity compared
      with responses to red light, with a significant linear correlation observed
      between pupil diameter and HVF mean deviation (r = -0.44; P = 0.005) as well as
      HRT linear cup-to-disc ratio (r = 0.61; P < 0.001) and several other optic nerve
      head parameters. CONCLUSIONS: In glaucomatous eyes, reduced pupillary responses
      to high-irradiance blue light were associated with greater visual field loss and
      optic disc cupping. In POAG, a short chromatic pupillometry test that evaluates
      the function of ipRGCs can be used to estimate the degree of damage to retinal
      ganglion cells that mediate image-forming vision. This approach could prove
      useful in detecting glaucoma.

PMID- 26299722
TI  - Multimodal Imaging in Multiple Evanescent White Dot Syndrome.

PMID- 26299723
TI  - En Face Optical Coherence Tomography of Subfoveal Perfluorocarbon Liquid.

PMID- 26299724
TI  - Neglected Basal Cell Carcinoma.

PMID- 26299725
TI  - Author reply: To PMID 25109931.

PMID- 26299726
TI  - Re: Wu et al.: Optical coherence tomography-defined changes preceding the
      development of drusen-associated atrophy in age-related macular degeneration
      (Ophthalmology 2014;121:2415-22).

PMID- 26299727
TI  - Re: Holland et al.: Antibiotic resistance in acute postoperative endophthalmitis
      (Ophthalmology 2014;121:S1-S9).

PMID- 26299728
TI  - Re: Conart et al.: Outcomes of macular hole surgery with short-duration
      positioning in highly myopic eyes: a case-control study (Ophthalmology
      2014;121:1263-8).

PMID- 26299729
TI  - Author reply: To PMID 24480709.

PMID- 26299730
TI  - Re: Maurino et al.: Quality of vision after bilateral multifocal intraocular lens
      implantation: a randomized trial - AT LISA 809M versus AcrySof ReSTOR SN6AD1
      (Ophthalmology 2015;122:700-10).

PMID- 26299731
TI  - Author reply: To PMID 25537197.

PMID- 26299732
TI  - Phosphorus-doped CoS2 nanosheet arrays as ultra-efficient electrocatalysts for
      the hydrogen evolution reaction.
AB  - In this communication, we, for the first time, prepared phosphorus-doped cobalt
      disulfide nanosheets as highly advanced electrocatalysts for the hydrogen
      evolution reaction. It was demonstrated that P doping could significantly enhance
      the electrocatalytic performance of CoS2 nanosheets in terms of onset
      overpotential, Tafel slope, exchange current density, and stability. 

PMID- 26299733
TI  - Effect of emulsifier and viscosity on oil separation in ready-to-use therapeutic
      food.
AB  - Oil separation is a common food quality problem in ready-to-use therapeutic food
      (RUTF), the shelf-stable, peanut-based food used to treat severe acute
      malnutrition in home settings. Our objective was to evaluate the effect on oil
      separation of three emulsifiers at different concentrations in RUTF. We also
      assessed two viscosity measurements. A scale-up experiment was carried out during
      full-scale RUTF production in Malawi. Results indicate that viscosity is
      inversely correlated with oil separation, and that the Bostwick consistometer is
      a simple, useful tool to predict viscosity. Oil separation in RUTF may be
      mitigated by use of an emulsifier, which increases the viscosity of the product.
      The emulsifier that reduced oil separation to the greatest extent was a mixture
      of high and low monoacylglycerol (MAG) emulsifiers. Proper raw material quality
      control to achieve consistent ingredient fat level and fat type, and production
      temperature and shearing control should be a focus in RUTF manufacturing. 

PMID- 26299734
TI  - Terrenolide S, a new antileishmanial butenolide from the endophytic fungus
      Aspergillus terreus.
AB  - Terrenolide S, a new butenolide derivative (6), together with six known
      compounds: (22E,24R)-stigmasta-5,7,22-trien-3-beta-ol (1), stigmast-4-ene-3-one
      (2), stigmasta-4,6,8(14),22-tetraen-3-one (3), terretonin A (4), terretonin (5)
      and butyrolactone VI (7) have been isolated from the endophytic fungus
      Aspergillus terreus isolated from the roots of Carthamus lanatus (Asteraceae).
      Their structures were established by extensive spectroscopic analyses (1D, 2D NMR
      and HRESIMS), as well as optical rotation measurement and comparison with
      literature data. Compound 1 displayed a potent activity towards methicillin
      resistant Staphylococcus aureus (MRSA) and Cryptococcus neoformans with IC50
      values of 2.29 and 10.68 uM, respectively. Moreover, 1, 2 and 6 exhibited
      antileishmanial activity towards Leishmania donovani with IC50 values of 11.24,
      15.32 and 27.27 uM, respectively and IC90 values of 14.68, 40.56 and 167.03 uM,
      respectively.

PMID- 26299735
TI  - Defining ambulatory bouts in free-living activity: Impact of brief stationary
      periods on bout metrics.
AB  - The aim of this study was to assess the effect of varying the maximum resting
      period between consecutive ambulatory bouts in community-based outcomes.
      Ambulation was assessed in 97 community-dwelling older adults (mean (SD) age 69.2
      (7.7) years) using an accelerometer (activPALTM) worn on the upper thigh for 7
      consecutive days. The volume, pattern and variability of ambulation were
      calculated over a range of maximum resting periods (1-30s). Outcomes with a
      maximum resting period from 1 to 6s did not vary due to device functionality. Non
      linear regression (power law, r(2) > 0.99) showed that increasing the maximum
      resting period from 6 to 30s resulted in changes in volume (increased duration
      spent walking, and decreased number of bouts), variability (S2 increased) and
      pattern (alpha decreased), and a linear relationship with an increase in average
      bout length. With a MRP of 6s, 6% of the cohort achieved the public health
      guidelines of 150 min of ambulation/week accumulated in bouts >= 10 min, which
      increased to 40% using a maximum resting period of 30s. Modifying the maximum
      resting period impacts on volume, pattern and variability measures of community
      based ambulation, and attainment of public health guidelines. This highlights the
      need for standardised algorithms to aid interpretation and explicit reporting of
      the maximum resting period to aid comparison between studies.

PMID- 26299736
TI  - U@C28: the electronic structure induced by the 32-electron principle.
AB  - First principles calculations show that the neutral U@C28 has a (cage)(2) ground
      state with Td symmetry instead of the long believed (5f)(1)(cage)(1) ground state
      with D2 symmetry. Its 34 valence electrons preferentially obey the 32-electron
      principle which fills all the s-, p-, d-, and f-type valence shells of the
      uranium atom. The remaining two valence electrons cannot break the electronic
      configuration and thus are located on the cage. 

PMID- 26299737
TI  - [Modern Nanomedicine in Treatment of Lung Carcinomas].
AB  - BACKGROUNDS: Despite the fast development of new effective cytostatics and
      targeted therapy, the treatment efficiency of lung cancer is still insufficient.
      The systemic administration of drugs results in a decrease in drug concentrations
      in tumor site, particularly due to specific extracellular environment in lungs.
      Nanotransporters could serve as a platform, protecting a drug against these
      undesired effects, which may enhance its therapeutic index and reduce side
      effects of a drug. Moreover, nanotechnologies possess the potential to improve
      the diagnostics of lung cancer, and thus increase a survival rate of oncologic
      patients. AIM: The presented study is aimed to demonstrate the possibilities
      provided by nanotechnologies in the field of treatment and diagnostic of lung
      cancers and discuss the obstacles, which complicate a translation into clinical
      practice.

PMID- 26299738
TI  - [Potential of Cell-free Circulating DNA in Diagnosis of Cancer].
AB  - Circulating cell-free DNA (cf-DNA) is characterized as extracellular DNA that may
      be present in the blood of healthy individuals in low concentrations. Cf-DNA is
      released by apoptosis or necrosis into the bloodstream. Increased levels are
      found in pathological conditions, such as inflammation, autoimmune diseases, or
      stress. Significant increase of cf-DNA is particularly evident in patients with
      malignancies, especially in the advanced stages of the disease. In this case, the
      tumor specific cf-DNA is released by necrosis from the cells of primary tumor and
      metastases. Recently, many studies concentrate on the so-called 'liquid biopsies'
      that allow detection of circulating tumor cells and circulating nucleic acids
      from peripheral blood for tumor diagnostics. Quantitative methods and detection
      of genetic and epigenetic alternations of cf-DNA in patients with different
      malignancies have potential applications in molecular diagnosis, prognosis,
      monitoring of disease progression and response to treatment. This review focuses
      on potential utility of cf-DNA as a blood biomarker in selected solid tumors and
      hematologic malignancies.

PMID- 26299739
TI  - [The Possibility of Epidermal Growth Factor Receptor Inhibition in Anal Cancer].
AB  - Anal cancer is a relatively rare tumour. In local and locally advanced disease,
      concomitant chemoradiation based on mitomycin C and 5-fluorouracil, remains
      golden standard of treatment. However, this treatment is associated with
      significant morbidity. With the developing of molecular biology, new treatment
      strategies can be investigated. Epidermal growth factor receptor (EGFR)
      expression in anal cancer is observed in 55-100% of cases. Some studies
      demonstrated that KRAS mutations, mechanism marker of resistance to antiEGFR
      therapy, are rare in anal cancer. This paper presents current view on the
      possibilities of antiEGFR therapy in locally advanced and metastatic anal cancer.

PMID- 26299740
TI  - [Cost-effectiveness Analysis of Panitumumab Plus mFOLFOX6 Compared to Bevacizumab
      Plus mFOLFOX6 for First-line Treatment of Patients with Wild-type RAS Metastatic
      Colorectal Cancer--Czech Republic Model Adaptation].
AB  - BACKGROUND: Pharmacoeconomic assessments are a part of the decision process not
      only during reimbursement setting, but in clinical practice as well. The
      presented cost-effectiveness analysis assesses panitumumab+mFOLFOX6 vs.
      bevacizumab+mFOLFOX6 in 1st line treatment of patients with wildtype RAS
      metastatic colorectal cancer (mCRC) in the Czech environment. MATERIAL AND
      METHODS: The adaptation of a Markov model considers the healthcare perspective;
      clinical data (efficacy, healthcare utilization and adverse events) are derived
      from a head-to-head comparison (PEAK study). Health states included in the model:
      progression free on treatment, progression (with/ without active treatment),
      resection of metastases, disease-free after successful resection and death.
      Actual reimbursement levels were used to estimate costs, published literature to
      estimate duration of 2nd line treatment. The analysis assumes a lifetime horizon;
      uncertainty was limited by performing one-way and probabilistic sensitivity
      analyses. Analysis outcomes are life-years gained (LYG) and quality-adjusted life
      years (QALYs). RESULTS: Panitumumab+mFOLFOX6 is more effective and more costly in
      1st line patients with wildtype RAS mCRC. Incremental costs per QALY are 837,270
      CZK, per LYG 615,022 CZK; however, below the willingness-to-pay threshold applied
      in the Czech Republic. CONCLUSIONS: Panitumumab+mFOLFOX6 is cost-effective in 1st
      line treatment of patients with wildtype RAS mCRC compared to
      bevacizumab+mFOLFOX6 in the Czech setting.

PMID- 26299741
TI  - Estimated Glomerular Filtration Rate in Oncology Patients before Cisplatin
      Chemotherapy.
AB  - BACKGROUND: The aim of the study is to compare measured glomerular filtration
      rate by technetium radiolabled diethylene tiamine pentaacetic acid (mGFR DTPA) to
      estimated GFR (eGFR). Glomerular filtration rate (GFR) is estimated from serum
      creatinine (eGFRcreatinine), serum cystatin C (eGFRcystatin C) and by combined
      equation (eGFRcreatinine+cystatin C). This study focuses on oncology patients
      considered for treatment with cisdiamminedichloroplatinum (cisplatin). We
      evaluated the impact of different GFR methods on the reduction of cisplatin dose.
      PATIENTS AND METHODS: The study population consisted of 112 consecutive oncology
      patients from oncology center treated in the town of Zlin in the Czech Republic,
      who were considered for cisplatin treatment. mGFR DTPA was performed by dynamic
      renal 99mTc scintigraphy method using diethyltriaminepentaacetic acid. Creatinine
      and cystatin C were determined by newly standardized tests. Estimation of GFR was
      calculated using The Chronic Kidney Disease Epidemiology (CKD EPI) equations
      which were established in 2009 and 2012. RESULTS: The median (interquartile
      range) of mGFR DTPA was 1.335 ml/s/1.73 m2 (1.070-1.725). The median of
      eGFRcystatin C 1.195 ml/s/1.73 m2 (0.885-1.625) was lower than mGFR DTPA
      (p<0.05). The median of eGFRcreatinine 1.460 ml/s/1.73 m2 (1.210-1.660) was
      higher than mGFR DTPA (p<0.05). Correlation analysis and Bland Altman plots show
      high individual differences between mGFR DTPA and all eGFRs. CONCLUSIONS:
      Oncology patients are a very special group of patients who dif-fer from general
      population. There are significant individual differences between mGFR DTPA and
      all eGFRs, impacting detection rate of CKD and potential drug dosage adjustment.

PMID- 26299742
TI  - Incidence and Prognostic Value of Known Genetic Aberrations in Patients with
      Acute Myeloid Leukemia--a Two Year Study.
AB  - BACKGROUND: In this work, we evaluated the incidence and prognostic value of
      several genetic aberrations in patients with a diagnosis of acute myeloid
      leukemia (AML). PATIENTS AND METHODS: We analysed 90 patients: 42 males (mean age
      54.5 years) and 48 females (mean age 59 years), with AML. The genetics of all
      leukemia samples was studied using conventional cytogenetics, the interphase
      fluorescence in situ hybridisation as well as the standardized RTPCR protocol.
      RESULTS: In 34.4% of patients, we detected at least one of the analysed genetic
      aberrations, except the CBFB MYH11, which we did not detect. Translocation
      t(8;21)/ AML1 ETO was found in 4.4% of patients with a mean age of 45.4 years,
      while none of these patients was older than 55 years. Translocation t(15;17)/
      PMLRARA was found in 5.5% of patients with a mean age of 52.6 years and an almost
      equal distribution between younger and older patients. The MLL gene
      rearrangements were found in 6.6% of patients, the -5/ 5q- and/ or -7/ 7q-
      aberrations in 7.7% of patients, while the most frequent genetic abnormality in
      our study was trisomy 8 (10%). Moreover, we found a favorable clinical outcome in
      patients expressing fusion genes AML1-ETO or PMLRARA in contrast to an adverse
      clinical outcome with few remissions and death in AML patients with MLL, -5q/ -5
      and -7q/ 7-. Finally, an intermediate prognosis was found in patients with
      trisomy 8. CONCLUSION: In this study, we found a good congruence with published
      literature on the incidence and prognostic value of several well established AML
      associated genetic aberrations. This simple genetic-based classification system
      helps us to identify patients with a favorable, intermediate or unfavorable
      prognosis and to treat them with the best currently available therapy. However,
      analysis of new genetically defined abnormalities in AML is necessary for
      development of better therapeutic strategies and/or diagnostics.

PMID- 26299743
TI  - [Extraoseus Ewings Sarcoma, Primary Affection of Uterine Cervix--Case Report].
AB  - BACKGROUND: Ewing's sarcoma is usually diagnosed in adolescents and young adults,
      peak of incidence is around 15 years of age. Primary localization is mostly in
      the skeleton of long bones and chest wall. Primary extraosseous involvement
      rarely occurs, incidence increases with age. CASE: We present a case report of a
      57-year-old patient with locally advanced tumors of the cervix, clinical stage
      IIB. Due to histological and molecular genetic examination revealing EWS -ERG
      fusion gene, Ewing's sarcoma was diagnosed. CT revealed pathological pelvic
      lymphadenopathy and multiple pulmonary bilateral methastases, scintigraphy did
      not prove any affection of skeleton. The patient underwent a two-stage intensive
      chemotherapy regimens VIDE (vincristine, ifosfamide, doxorubicin, etoposide) and
      VAI (vincristine, actinomycin D, ifosfamide). During the second phase,
      concomitant radiotherapy of pelvis was aplied. According to PET/CT, complete
      remission was achieved. Whole-lung irradiation was applied in consolidation of
      the result. CONCLUSION: Primary Ewing's sarcoma of the cervix is an extremely
      rare disease. To our knowledge, only 12 cases was presented until this time. The
      average age at time of dia-gnosis was 35 years. Unlike the previous reports, we
      initially diagnosed distant metastases. The treatment was led according to the
      protocol Ewing 2008 designed for primary skeletal Ewing's sarcoma. Currently, 18
      months after the therapy, the patient is without signs of disease. However, long
      term follow-up is necessary.

PMID- 26299744
TI  - [Embryonal Tumors with Multilayer Rosettes--Rare Central Nervous System Tumors in
      Infants].
AB  - INTRODUCTION: The most recent findings show a histopathological, genetic and
      clinical uniformity in cases of tumors called embryonal tumors with multilayer
      rosettes. This group is composed of medulloepithelioma, ependymoblastoma and
      embryonal tumor with abundant neuropil and true rosettes. Amplification of locus
      19q13.42, which includes C19MC cluster containing genes for microRNA, and also
      LIN28A positivity are present in all three entities. Dysregulation of epigenetic
      modifiers is very important in pathogenesis of the disease. These tumors manifest
      in little children (median less than 3 years of age); overall survival is 5-10%.
      CASE REPORT: Almost three year-old boy diagnosed with brainstem tumor:
      meduloepithelioma, WHO grade IV confirmed by histological investigation. He
      presented with dysarthria, bulbar syndrome, central lesion of the facial nerve,
      quadriparesis with right-side dominancy. He received three induction cycles of
      chemotherapy from March to May 2014 (according to protocol COG ACNS0334). Only
      partial improvement of his clinical state was reached. Signs of an intracranial
      hypertension appeared resulting in VP shunt insertion; impairment of
      consciousness developed after the induction cycles and before any other treatment
      could be initiated. He underwent radiotherapy due to vital indication. After
      application of two fractions (boost in the center of the tumor), the patient
      became quickly comatose. Spinal cord metastasis was demarked by MRI scan (in the
      level of 3rd cervical vertebra). A bilateral infiltration in pulmonary
      parenchyma, according to a radiologist metastasis-wise, was detected by CT scan
      (histologisation of infiltration was not implemented). The patient died in August
      2014--six months after manifestation of first symptoms. CONCLUSION: We reported
      our first documented case of a patient with tumor from embryonal tumors with
      multilayer rosettes group in Slovakia. Nowadays, there is no effective treatment
      of these tumors. Research of molecules targeting to epigenetic modifiers would be
      one of the possible promises for future therapy.

PMID- 26299745
TI  - [Anticoagulation and Thrombembolism During Bevacizumab Treatment--To Be Careful
      or Fearful?].
AB  - Inhibition of angiogenesis is a valid approach in today's medicine. Besides
      oncology, it is used in ophthalmology, as well. In oncology, angiogenesis
      inhibition has become a routine and accessible method. A combination of
      angiogenesis inhibition and other therapies, including anticoagulation and
      antiaggregation is common in many cases. Bevacizumab is the most used
      antiangiogenic agent and has been in use for the longest period of time. A
      concomitant administration of angiogenesis inhibitors and anticoagulation may be
      feared by oncologists. From the available literature it is obvious that
      concomitant administration of bevacizumab and anticoagulation is safe. Also, use
      of antiaggregation and bevacizumab is safe. The risk of venous and arterial
      thromboembolism is real during the treatment with bevacizumab. Therefore,
      concomitant anticoagulation is not only possible but also may be desirable.

PMID- 26299746
TI  - New concepts in basement membrane biology.
AB  - Basement membranes (BMs) are thin sheets of extracellular matrix that outline
      epithelia, muscle fibers, blood vessels and peripheral nerves. The current view
      of BM structure and functions is based mainly on transmission electron microscopy
      imaging, in vitro protein binding assays, and phenotype analysis of human
      patients, mutant mice and invertebrata. Recently, MS-based protein analysis,
      biomechanical testing and cell adhesion assays with in vivo derived BMs have led
      to new and unexpected insights. Proteomic analysis combined with ultrastructural
      studies showed that many BMs undergo compositional and structural changes with
      advancing age. Atomic force microscopy measurements in combination with phenotype
      analysis have revealed an altered mechanical stiffness that correlates with
      specific BM pathologies in mutant mice and human patients. Atomic force
      microscopy-based height measurements strongly suggest that BMs are more than two
      fold thicker than previously estimated, providing greater freedom for modelling
      the large protein polymers within BMs. In addition, data gathered using BMs
      extracted from mutant mice showed that laminin has a crucial role in BM
      stability. Finally, recent evidence demonstrate that BMs are bi-functionally
      organized, leading to the proposition that BM-sidedness contributes to the
      alternating epithelial and stromal tissue arrangements that are found in all
      metazoan species. We propose that BMs are ancient structures with tissue
      organizing functions and were essential in the evolution of metazoan species. 

PMID- 26299747
TI  - Thrombosis Research Editorial.

PMID- 26299748
TI  - Monolayer kinetic model of formation of beta-cyclodextrin-beta-carotene inclusion
      complex.
AB  - The carotenoids are sensitive molecules and their chemical integrity must be
      preserved from pro-oxidant elements which could affect and decrease their
      physiological benefits. The encapsulation based on the inclusion of the
      carotenoids into cage molecules is a promising approach for preserving over time
      of the intrinsic properties of the carotenoids. It is well known that cyclic
      oligosaccharide beta-cyclodextrin (CD) as a cage molecule possesses strong
      inclusion ability to beta-carotene (C) and as a result of the hydrophobic
      interactions forms an inclusion complex. In the present paper a monolayer kinetic
      model was established with the notion to extract more information about the
      influence of the molecular structure and organization to the interfacial
      interactions between the interacting species as well as about the role of the
      specific areas, which are often underestimated in previously studied dispersed
      systems. We developed the monolayer kinetic model for the formation of the
      inclusion CD-C complex by applying an experimental approach for following the
      kinetics by means of measuring the decrease of the surface area (DeltaA) versus
      time (t) at constant surface pressure (pi) and the decrease of surface pressure
      (pi) versus time (t) at constant surface area (A). We also visualized by AFM the
      state of the monolayers at the initial and end points of the kinetic process. The
      values for the degree (d) and constant (Ka) of the association were estimated and
      compared with those from the studies of dispersed systems. 

PMID- 26299749
TI  - Epidemiology of serogroup C and Y invasive meningococcal disease (IMD) in
      Ontario, 2000-2013: Vaccine program impact assessment.
AB  - OBJECTIVES: A publicly-funded meningococcal serogroup C conjugate vaccine (MCCV)
      program was introduced in Ontario, in 2004/2005 for 1-year-old children as well
      as adolescents (approximately 12 years old). In 2009, quadrivalent meningococcal
      conjugate vaccine (MCV4) replaced MCCV for grade seven students. Our objective
      was to determine meningococcal vaccine program impact on reported cases of
      serogroup C and Y invasive meningococcal disease (IMD) at the population level in
      Ontario, Canada. METHODS: Data were obtained from the Ontario reportable diseases
      system, the integrated Public Health Information System (iPHIS), and Public
      Health Ontario Laboratories (PHOL) for 2000-2013. Descriptive epidemiologic
      analyses, including age-specific rates for age groups based on program
      eligibility, were conducted. Changes over the 14-year observation period and
      comparison of pre- and post-program periods for MCCV and MCV4 were assessed.
      Analyses were conducted using SAS 9.3. RESULTS: There were 161 serogroup C IMD
      cases and its annual incidence decreased significantly over time (17.2% reduction
      per year [95% CI: 13.4 to 20.7]). The incidence of serogroup C IMD decreased
      significantly in children aged 1-17 years in the post-program period, based on
      age-specific incidence rate ratios (IRRs) and their 95% confidence intervals
      (CIs). Adolescents 12-16 years had the lowest serogroup C IRR (0.07 [95% CI: 0.01
      to 0.55]); the rate decreased more than 14-fold between the pre- and post
      periods. There were 187 serogroup Y IMD cases and there was a non-significant
      1.6% reduction per year [95% CI: -1.9 to 5.1]) over the surveillance period.
      Likewise, there was a non-significant decrease in serogroup Y IMD among persons
      12-16 years (MCV4 eligible) in the post-program period. CONCLUSIONS: Reductions
      in serogroup C IMD among program eligible and ineligible age groups suggest both
      direct and indirect MCCV vaccine program impact. Continued surveillance of IMD in
      Ontario is important to further assess MCV4 program impact.

PMID- 26299751
TI  - Task- and Context-Specific Balance Training Program Enhances Dynamic Balance and
      Functional Performance in Parkinsonian Nonfallers: A Randomized Controlled Trial
      With Six-Month Follow-Up.
AB  - OBJECTIVES: To investigate the short- and long-term effects of a task- and
      context-specific balance training program on dynamic balance and functional
      performance, and to explore the effects on preventing total and injurious falls
      in parkinsonian nonfallers. DESIGN: A randomized controlled trial with group
      allocation single-blinded to the assessor. SETTING: Community centers, malls, and
      outdoor parks. PARTICIPANTS: Nonfallers with Parkinson disease (PD) (N=70; mean
      age +/- SD, 61.2+/-8.8y) randomly assigned to either a balance (BAL) group (n=32)
      or a control (CON) group (n=38). INTERVENTIONS: The BAL group received 4 weeks of
      indoor and 4 weeks of outdoor balance training (with a 2-h session per week). The
      CON group received 8 weeks of upper limb training at the same dosage. Both groups
      were instructed to perform 3 hours of home exercise weekly posttraining. MAIN
      OUTCOME MEASURES: (1) Dynamic balance performance: Mini-Balance Evaluation
      Systems Test (Mini-BESTest); (2) Functional performance: functional reach (FR), 5
      times sit-to-stand (FTSTS), 1-leg-stance (OLS), Timed Up and Go (TUG), and dual
      task TUG tests; (3) Fall-related outcomes: ratios of total nonfallers to fallers
      and noninjurious fallers to injurious fallers, total and injurious fall rates,
      times to first falls and injurious falls. RESULTS: Sixty-eight participants
      completed training. A total of 7 patients (10%) withdrew before the 6-month
      follow-up, but not because of any adverse effects. At immediate and 6 months
      posttraining, the BAL group showed significantly greater improvements (from
      baseline) than the CON group in Mini-BESTest total scores, FR distances, and OLS
      times, together with greater time reductions in FTSTS, TUG, and dual-task TUG
      tests (all P<.05). The number of injurious fallers was significantly lower in the
      BAL group at 6-month follow-up. CONCLUSIONS: This task- and context-specific
      balance training program improved the dynamic balance and fall-prone functional
      performance of PD nonfallers for up to 6 months after training. The BAL group
      showed a reduction in injurious fallers.

PMID- 26299750
TI  - Nanovaccines for malaria using Plasmodium falciparum antigen Pfs25 attached gold
      nanoparticles.
AB  - Malaria transmission-blocking vaccines (TBV) targeting sexual stages of the
      parasite represent an ideal intervention to reduce the burden of the disease and
      eventual elimination at the population level in endemic regions. Immune responses
      against sexual stage antigens impair the development of parasite inside the
      mosquitoes. Target antigens identified in Plasmodium falciparum include surface
      proteins Pfs230 and Pfs48/45 in male and female gametocytes and Pfs25 expressed
      in zygotes and ookinetes. The latter has undergone extensive evaluation in pre
      clinical and phase I clinical trials and remains one of the leading target
      antigens for the development of TBV. Pfs25 has a complex tertiary structure
      characterized by four EGF-like repeat motifs formed by 11 disulfide bonds, and it
      has been rather difficult to obtain Pfs25 as a homogenous product in native
      conformation in any heterologous expression system. Recently, we have reported
      expression of codon-harmonized recombinant Pfs25 in Escherichia coli (CHrPfs25)
      and which elicited highly potent malaria transmission-blocking antibodies in
      mice. In the current study, we investigated CHrPfs25 along with gold
      nanoparticles of different shapes, size and physicochemical properties as
      adjuvants for induction of transmission blocking immunity. The results revealed
      that CHrPfs25 delivered with various gold nanoparticles elicited strong
      transmission blocking antibodies and suggested that gold nanoparticles based
      formulations can be developed as nanovaccines to enhance the immunogenicity of
      vaccine antigens.

PMID- 26299752
TI  - Measuring Patients' Experience of Rehabilitation Services Across the Care
      Continuum. Part I: A Systematic Review of the Literature.
AB  - OBJECTIVE: To identify empirically tested survey instruments designed to measure
      patient experience across a rehabilitative care system. DATA SOURCES: A
      comprehensive search was conducted of the MEDLINE (PubMed), CINAHL (EBSCO), and
      PsycINFO (APA PsycNET) databases from 2004 to 2014. Further searches were
      conducted in relevant journals and the reference lists of the final accepted
      articles. STUDY SELECTION: Of 2472 articles identified, 33 were selected for
      inclusion and analysis. Articles were excluded if they were unrelated to
      rehabilitative care, were anecdotal or descriptive reports, or had a veterinary,
      mental health, palliative care, dental, or pediatric focus. Four reviewers
      performed the screening process. Interrater reliability was confirmed through 2
      rounds of title review (30 articles each) and 1 round of abstract review (10
      articles), with an average kappa score of .69. DATA EXTRACTION: Data were
      extracted related to the instrument, study setting, and patient characteristics,
      including treated disease, type of rehabilitation (eg, occupational or physical
      therapy), methodology, sample size, and level of evidence. DATA SYNTHESIS: There
      were 25 discrete measurement instruments identified in the 33 articles evaluated.
      Seven of the instruments originated outside of the rehabilitative care sector,
      and only 1 measured service experience across the care continuum. CONCLUSIONS: As
      providers move to integrate rehabilitative care across the continuum from
      hospital to home, patients experience a system of care. Research is required to
      develop psychometrically tested instruments that measure patients' experience
      across a rehabilitative system.

PMID- 26299753
TI  - Hyponatremia, hypo-osmolality, and seizures in children early post-kidney
      transplant.
AB  - Post-transplant seizures are uncommon in young kidney transplant recipients but
      can be harbingers of devastating outcomes such as cerebral edema and death. We
      reviewed all transplants performed at our institution from January 2013 to
      January 2014 and compared three patients who seized within 24 h post-transplant
      (cases) with the remaining 33 transplant recipients (controls). Records were
      reviewed for hyponatremia, hypocalcemia, hypomagnesemia, BUN clearance,
      osmolality shifts, and blood pressure control in the first 24 h post-transplant.
      All cases had more pronounced (p < 0.001) shifts in serum sodium and calculated
      serum osmolality, with their sodium decreasing by >15 mmol/L to nadir values of
      124, 131, and 131 mmol/L, respectively. There were no differences in serum
      calcium corrected for hypoalbuminemia, serum magnesium, urine output, or blood
      pressure control between the groups. Our study suggests that mild hyponatremia
      and an acute decrease in serum osmolality are risk factors for potentially severe
      postoperative neurologic complications following kidney transplantation. Thus,
      peri-transplant management should be optimized to anticipate and prevent these
      abnormalities.

PMID- 26299754
TI  - Bacillus amyloliquefaciens AG1 biosurfactant: Putative receptor diversity and
      histopathological effects on Tuta absoluta midgut.
AB  - The use of biosurfactant in pest management has received much attention for the
      control of plant pathogens, but few studies reported their insecticidal activity.
      The present study describes the insecticidal activity of biosurfactant extracted
      from Bacillus amyloliquefaciens strain AG1. This strain produces a lipopeptide
      biosurfactant exhibiting an LC50 of about 180ng/cm(2) against Tuta absoluta
      larvae. Accordingly, the histopathologic effect of this biosurfactant on T.
      absoluta larvae showed serious damages of the midgut tissues including rupture
      and disintegration of epithelial layer and cellular vacuolization. By PCR, we
      showed that this biosurfactant could be formed by several lipopeptides and
      polyketides including iturin, fengycin, surfactin, bacyllomicin, bacillaene,
      macrolactin and difficidin. Binding experiment revealed that it recognized five
      putative receptors located in the BBMV of T. absoluta with sizes of 68, 63, 44,
      30 and 19kDa. Therefore, biosurfactant AG1 hold potential for use as an
      environmentally friendly agent to control the tomato leaf miner. 

PMID- 26299755
TI  - Agricultural nematology in East and Southern Africa: problems, management
      strategies and stakeholder linkages.
AB  - By 2050, Africa's population is projected to exceed 2 billion. Africa will have
      to increase food production more than 50% in the coming 50 years to meet the
      nutritional requirements of its growing population. Nowhere is the need to
      increase agricultural productivity more pertinent than in much of Sub-Saharan
      Africa, where it is currently static or declining. Optimal pest management will
      be essential, because intensification of any system creates heightened selection
      pressures for pests. Plant-parasitic nematodes and their damage potential are
      intertwined with intensified systems and can be an indicator of unsustainable
      practices. As soil pests, nematodes are commonly overlooked or misdiagnosed,
      particularly where appropriate expertise and knowledge transfer systems are
      meager or inadequately funded. Nematode damage to roots results in less efficient
      root systems that are less able to access nutrients and water, which can produce
      symptoms typical of water or nutrient deficiency, leading to misdiagnosis of the
      underlying cause. Damage in subsistence agriculture is exacerbated by growing
      crops on degraded soils and in areas of low water retention where strong root
      growth is vital. This review focuses on the current knowledge of economically
      important nematode pests affecting key crops, nematode control methods and the
      research and development needs for sustainable management, stakeholder
      involvement and capacity building in the context of crop security in East and
      Southern Africa, especially Kenya, Tanzania, Uganda and Zimbabwe.

PMID- 26299757
TI  - Golfer's purpura - an under recognised form of exercise-induced capillaritis.

PMID- 26299756
TI  - Structural insights into tumor-specific chaperoning activity of gamma synuclein
      in protecting estrogen receptor alpha 36 and its role in tamoxifen resistance in
      breast cancer.
AB  - Gamma synuclein (gammaSyn), a tumor-specific molecular chaperone, protects Hsp90
      client proteins like ERalpha36 and stimulates rapid membrane-initiated estrogen
      signalling in breast cancer cells. However, the structural perspectives of this
      tumor-specific chaperone function of gammaSyn remains unclear. Hence, in this
      present work, we studied the conformational dynamics of ERalpha36 in the absence
      and presence of Hsp90 and gammaSyn. Results indicate that in a chaperone-free
      state, ERalpha36 undergoes an inter-domain movement and exposes the hydrophobic
      patch of residues that are responsible for binding with ubiquitin. However,
      independent of Hsp90, gammaSyn, by establishing transient interactions, prevents
      interdomain movement, unveils the co-activator binding groove, masks the
      ubiquitin-binding residues and maintains 'open' pocket conformation of LBD. By
      doing so, gammaSyn effectively protects ERalpha36 from degradation and maintains
      its functional state like Hsp90 based chaperoning machinery but independent of
      ATP. Our studies also show that the gammaSyn protected conformation of ERalpha36
      can effectively bind with both estradiol (E2) and 4-hydroxy tamoxifen (4-OHT).
      Although they exhibit unique binding modes, they maintained the functionally
      active conformation of ERalpha36. Interestingly, the molecular dynamics
      simulation studies showed that 4-OHT, like gammaSyn, prevented the interdomain
      movements, primes the co-activator binding groove of ERalpha36 for complexation
      with downstream signalling proteins and this mechanism explains its agonist
      activity and associated anti-estrogen resistance observed in the presence of
      ERalpha36. The observed differences in the chaperoning mechanism of gammaSyn
      sheds light on its selectivity over Hsp90 in cancer cells, for promoting rapid
      protection of crucial oncogenic proteins. Based on our findings, we speculate
      that the compounds, which can hamper association of gammaSyn with ERalpha36
      and/or can arrest ERalpha36 in an ubiquitin binding state, would be promising
      alternatives for treating ERalpha36 expressed breast carcinomas. 

PMID- 26299758
TI  - Attention following traumatic brain injury: Neuropsychological and driving
      simulator data, and association with sleep, sleepiness, and fatigue.
AB  - The objectives of this study were to compare individuals with traumatic brain
      injury (TBI) and healthy controls on neuropsychological tests of attention and
      driving simulation performance, and explore their relationships with
      participants' characteristics, sleep, sleepiness, and fatigue. Participants were
      22 adults with moderate or severe TBI (time since injury >= one year) and 22
      matched controls. They completed three neuropsychological tests of attention, a
      driving simulator task, night-time polysomnographic recordings, and subjective
      ratings of sleepiness and fatigue. Results showed that participants with TBI
      exhibited poorer performance compared to controls on measures tapping speed of
      information processing and sustained attention, but not on selective attention
      measures. On the driving simulator task, a greater variability of the vehicle
      lateral position was observed in the TBI group. Poorer performance on specific
      subsets of neuropsychological variables was associated with poorer sleep
      continuity in the TBI group, and with a greater increase in subjective sleepiness
      in both groups. No significant relationship was found between cognitive
      performance and fatigue. These findings add to the existing evidence that speed
      of information processing is still impaired several years after moderate to
      severe TBI. Sustained attention could also be compromised. Attention seems to be
      associated with sleep continuity and daytime sleepiness; this interaction needs
      to be explored further.

PMID- 26299759
TI  - Interpretations of bullying by bullies, victims, and bully-victims in
      interactions at different levels of abstraction.
AB  - According to the Social Information Processing Model of children's adjustment,
      children develop general interpretation styles for future social events based on
      past social experiences. Previous research has shown associations between
      interpretations of social situations and internalizing and externalizing
      symptoms. This study investigated whether bullies, victims, bully-victims, and
      uninvolved children interpreted ambiguous human interactions differently in terms
      of bullying and whether these interpretations generalized to abstract non-human
      interactions. Participants were 390 children (49% girls, Mage  = 10.3 years) who
      completed self-report measures of bullying and victimization. In addition, they
      indicated whether video fragments of positive, negative, or ambiguous
      interactions between humans, animals, and abstract figures depicted bullying
      situations. Bully-victims reported more bullying than victims and uninvolved
      children in ambiguous abstract figure, animal, and human fragments and in
      positive animal fragments. Children who bully did not differ from the other
      groups. These findings indicate that interpretations of bullying generalized from
      ambiguous human interactions to more abstract ambiguous animal and abstract
      figure interactions. Implications for further research and practice were
      discussed.

PMID- 26299761
TI  - Comparative analysis of methods for real-time analytical control of
      chemotherapies preparations.
AB  - Control of chemotherapies preparations are now an obligation in France, though
      analytical control is compulsory. Several methods are available and none of them
      is presumed as ideal. We wanted to compare them so as to determine which one
      could be the best choice. We compared non analytical (visual and video-assisted,
      gravimetric) and analytical (HPLC/FIA, UV/FT-IR, UV/Raman, Raman) methods thanks
      to our experience and a SWOT analysis. The results of the analysis show great
      differences between the techniques, but as expected none us them is without
      defects. However they can probably be used in synergy. Overall for the pharmacist
      willing to get involved, the implementation of the control for chemotherapies
      preparations must be widely anticipated, with the listing of every parameter, and
      remains according to us an analyst's job. 

PMID- 26299763
TI  - Chemical interaction of water molecules with framework Al in acid zeolites: a
      periodic ab initio study on H-clinoptilolite.
AB  - Periodic quantum-chemistry methods as implemented in the CRYSTAL14 code were
      considered to analyse the interaction of acid clinoptilolite with water.
      Initially adsorbed molecules hydrolyse the Al-O bonds, giving rise to defective
      dealuminated materials. A suitable and representative periodic model of the
      partially disordered hydrated H-zeolite is the primitive cell (18 T sites) of a
      decahydrated trialuminated structure of HEU topology. The water distribution
      inside the material cavities was initially investigated. The model considered for
      further dealumination was the most stable one from those generated through a
      combined force field Monte Carlo and ab initio optimization strategy.
      Optimizations and energy estimations were made at the hybrid DFT level of theory
      (PBE0 functional) with an atomic basis set of VDZP quality. The energetics of the
      different pathways involved in the dealumination process was addressed by
      considering the Gibbs free energy with thermal and zero-point corrections through
      phonon analysis. It arises that hydrated models exhibit protonated water clusters
      stabilized by different kinds of H-bonds. The first Al extraction is slightly
      more energetically favourable from T3 than T2 sites, but at the same time the
      latter is more probable owing to its larger Al population. However, concerning
      the second dealumination step, it is more favourable removing the Al atom from
      both remaining sites after a starting abstraction from T2 rather than T3. These
      facts determine that the most probable overall pathways go through a first Al
      removal from T2. The agreement with experimental results is discussed. 

PMID- 26299762
TI  - Targeting docetaxel-PLA nanoparticles simultaneously inhibit tumor growth and
      liver metastases of small cell lung cancer.
AB  - Small cell lung cancer (SCLC) is one of the most malignant cancers in the world
      and 5-year survival rate has not been significantly improved with conventional
      chemotherapy. Targeting treatment may be a promising alternative to enhance the
      antitumor efficacy. Present study was aimed at establishing a targeting nanodrug
      delivery system for SCLC therapy. A targeting peptide (AHSGMYP, named AP),
      screened in H446 cells by phage display technology, was conjugated to the
      docetaxel (DTX) encapsulated polylactic acid nanoparticles (DN) to prepare the
      targeting DTX nanoparticles (AP-DN). Cell cytotoxicity, cellular uptake,
      therapeutic efficacy and biodistribution of AP-DN were investigated in vitro and
      in vivo experiment. The mean particle size of AP-DN was 260 nm with encapsulation
      efficiency >94% and a sustained release profile. Cytotoxicity of AP-DN against
      H446 cell was superior to that of DTX and DN. AP-DN exhibited excellent antitumor
      efficacy and particularly effectively inhibited the liver metastases with better
      tolerance. Results of cellular uptake and biodistribution indicated that the
      excellent antitumor efficacy of AP-DN was attributed to both the increased
      accumulation of drug and cellular uptake. To our knowledge, this is the first
      report on establishing SCLC targeting delivery system which offers a potential
      therapeutic alterative for SCLC therapy.

PMID- 26299764
TI  - Two-way chromic interconversion of the 2,2'-biphenol-6,6'-diyl dication with
      5H,10H-dioxapyrene or 9H,10H-4,5-dihydroxyphenanthrene.
AB  - Two-proton or two-electron transfer of the title biphenolic dication proceeds
      nearly simultaneously to induce 2,6'/2',6- or 6,6'-bond formation to give
      dioxapyrene or dihydrophenanthrene derivatives, respectively, with vivid changes
      in color (halochromism and electrochromism). 

PMID- 26299765
TI  - Abnormal alterations in the Ca2+/CaV1.2/calmodulin/caMKII signaling pathway in a
      tremor rat model and in cultured hippocampal neurons exposed to Mg2+-free
      solution.
AB  - Voltage-dependent calcium channels (VDCCs) are key elements in epileptogenesis.
      There are several binding-sites linked to calmodulin (CaM) and several potential
      CaM-dependent protein kinase II (CaMKII)-mediated phosphorylation sites in
      CaV1.2. The tremor rat model (TRM) exhibits absence-like seizures from 8 weeks of
      age. The present study was performed to detect changes in the
      Ca2+/CaV1.2/CaM/CaMKII pathway in TRMs and in cultured hippocampal neurons
      exposed to Mg2+-free solution. The expression levels of CaV1.2, CaM and
      phosphorylated CaMKII (p-CaMKII; Thr-286) in these two models were examined using
      immunofluorescence and western blotting. Compared with Wistar rats, the
      expression levels of CaV1.2 and CaM were increased, and the expression of p
      CaMKII was decreased in the TRM hippocampus. However, the expression of the
      targeted proteins was reversed in the TRM temporal cortex. A significant increase
      in the expression of CaM and decrease in the expression of CaV1.2 were observed
      in the TRM cerebellum. In the cultured neuron model, p-CaMKII and CaV1.2 were
      markedly decreased. In addition, neurons exhibiting co-localized expression of
      CaV1.2 and CaM immunoreactivities were detected. Furthermore, intracellular
      calcium concentrations were increased in these two models. For the first time, o
      the best of our knowledge, the data of the present study suggested that abnormal
      alterations in the Ca2+/CaV1.2/CaM/CaMKII pathway may be involved in
      epileptogenesis and in the phenotypes of TRMs and cultured hippocampal neurons
      exposed to Mg2+-free solution.

PMID- 26299767
TI  - Surgical correction of a bilateral congenital tarsal hyperextension deformity in
      a cat.
AB  - CASE DESCRIPTION: An approximately three-month-old, 0.45 kg female Domestic
      Shorthaired kitten with stiff hyperextended hindlimbs distal to the talo-central
      joint is reported. Attempts at repositioning of the joints by flexion failed
      while increased manipulative forces caused signs of pain and vocalization.
      Orthogonal radiographic views revealed a significant malarticulation of the
      tarsus. Goniometric measurments revealed a 145 degrees  extensor and 95 degrees 
      internal torsional deformity. TREATMENT AND OUTCOME: Pantarsal arthrodesis with a
      transarticular external fixation system was performed for both limbs in two
      separate stages. Pre-assembled frames were composed of two 40 mm diameter half
      rings (on the medial side) and two 40 mm diameter full rings connected with two
      pre-contoured (125 degrees  flexion) rods from proximal to distal. Following
      transection of the superficial and deep digital flexor tendons, cartilage was
      removed from the articular surfaces, autologous cancellous bone graft was
      inserted, and joints were fixed in 125 degrees  flexion with pre-contured
      external frames. The cat commenced weight-bearing bilaterally immediately
      postoperatively. Frames were removed 32 and 27 days after application. Two months
      after frame removal, joint fusion was confirmed and full weight-bearing at the
      walk and run was achieved. CLINICAL RELEVANCE: To our knowledge, this is the
      first report of surgical correction of a bilateral congenital tarsal
      hyperextension deformity by pantarsal arthrodesis using a transarticular external
      fixation system.

PMID- 26299766
TI  - Targeting Mycobacterium tuberculosis Biotin Protein Ligase (MtBPL) with
      Nucleoside-Based Bisubstrate Adenylation Inhibitors.
AB  - Mycobacterium tuberculosis (Mtb), responsible for both latent and symptomatic
      tuberculosis (TB), remains the second leading cause of mortality among infectious
      diseases worldwide. Mycobacterial biotin protein ligase (MtBPL) is an essential
      enzyme in Mtb and regulates lipid metabolism through the post-translational
      biotinylation of acyl coenzyme A carboxylases. We report the synthesis and
      evaluation of a systematic series of potent nucleoside-based inhibitors of MtBPL
      that contain modifications to the ribofuranosyl ring of the nucleoside. All
      compounds were characterized by isothermal titration calorimetry (ITC) and shown
      to bind potently with K(D)s <= 2 nM. Additionally, we obtained high-resolution
      cocrystal structures for a majority of the compounds. Despite fairly uniform
      biochemical potency, the whole-cell Mtb activity varied greatly with minimum
      inhibitory concentrations (MIC) ranging from 0.78 to >100 MUM. Cellular
      accumulation studies showed a nearly 10-fold enhancement in accumulation of a C
      2'-alpha analogue over the corresponding C-2'-beta analogue, consistent with
      their differential whole-cell activity.

PMID- 26299768
TI  - MicroRNA-101 inhibits the migration and invasion of intrahepatic
      cholangiocarcinoma cells via direct suppression of vascular endothelial growth
      factor-C.
AB  - MicroRNAs (miRs) have important roles in the pathogenesis of human malignancy. It
      has previously been suggested that deregulation of miR-101 is associated with the
      progression of intrahepatic cholangiocarcinoma (ICC); however, the exact role of
      miR-101 in the regulation of ICC metastasis remains largely unknown. The present
      study demonstrated that the expression levels of miR-101 were significantly
      decreased in ICC tissue, as compared with matched adjacent normal tissue.
      Furthermore, miR-101 was downregulated in the ICC-9810 human ICC cell line, as
      compared with in the normal human intrahepatic biliary epithelial cell (HIBEC)
      line. Vascular endothelial growth factor (VEGF)-C was identified as a target gene
      of miR-101 in ICC-9810 cells. The expression of VEGF-C was negatively regulated
      by miR-101 at the post-transcriptional level in ICC-9810 cells. Further
      investigation demonstrated that overexpression of miR-101 markedly suppressed the
      migration and invasion of ICC-9810 cells, and these effects were similar to those
      observed following VEGF-C knockdown. Conversely, restoration of VEGF-C reversed
      the inhibitory effects of miR-101 overexpression on ICC-9810 cell migration and
      invasion, thus suggesting that miR-101 may suppress ICC-9810 cell migration and
      invasion, at least partly via inhibition of VEGF-C. It was also demonstrated that
      the mRNA and protein expression levels of VEGF-C were frequently upregulated in
      ICC tissue and cells, and its expression level was inversely correlated with that
      of miR-101 in ICC tissue. In conclusion, the present study identified important
      roles for miR-101 and VEGF-C in ICC, suggesting that miR-101/VEGF-C signaling may
      be a promising diagnostic and/or therapeutic target for ICC.

PMID- 26299769
TI  - Endobronchial aspergilloma: An unusual presentation of pulmonary aspergillosis.

PMID- 26299770
TI  - Selective Inhibition of SIRT2 Improves Outcomes in a Lethal Septic Model.
AB  - BACKGROUND: Seven isoforms of histone deacetylase Class III have been reported -
      Sirtuin (SIRT) 1-7. We recently demonstrated that EX-527, an inhibitor of SIRT1,
      reduces mortality in a mouse model of lethal-cecal-ligationand- puncture (CLP)
      induced septic shock. Our present study was aimed at determining whether
      selective inhibition of SIRT2, with AGK2, would decrease animal death and
      attenuate the inflammatory response in a septic model. METHODS: Experiment I:
      C57BL/6J mice were intraperitoneally given either AGK2 (82 mg/kg) in dimethyl
      sulfoxide (DMSO) or DMSO alone, and 2 h later subjected to CLP. Survival was
      monitored for 240 hours. Experiment II: mice treated the same way as Experiment
      I, were grouped into (i) DMSO vehicle, and (ii) AGK2, with sham mice (operating
      but without any treatment) serving as controls. Peritoneal fluid and peripheral
      blood were examined at 24 and 48 hours for cytokine production. Samples of blood
      at 48 h were also allocated to assess coagulability using Thrombelastography
      (TEG). Morphological changes of bone marrow were evaluated from long bones
      (femurs and tibias) with hematoxylin and eosin (H&E) staining. Bone marrow
      atrophy was quantified by a blinded pathologist. Experiment III: cytokines in
      supernatant of the cultured normal primary splenocytes were measured after the
      cells were stimulated by lipopolysaccharide and treated with or without AGK2 (10
      uM) for 6 hours. RESULTS: AGK2 significantly reduced mortality and decreased
      levels of cytokines in blood (TNF-alpha: 298.3+/-24.6 vs 26.8+/-2.8 pg/ml,
      p=0.0034; IL-6: 633.4+/-82.8 vs 232.6+/-133.0 pg/ml, p=0.0344) and peritoneal
      fluid (IL-6: 704.8+/-67.7 vs 391.4+/-98.5 pg/ml, p=0.033) compared to vehicle
      control. Also, AGK2 suppressed the TNF-alpha and IL-6 production in the cultured
      splenocytes (TNF-alpha: 68.1+/-6.4 vs 23.9+/-2.8 pg/ml, p=0.0009; IL-6: 73.1+/
      4.2 vs 49.6+/-3.0 pg/ml; p=0.0051). The TEG data showed that the mice subjected
      to CLP displayed prolonged fibrin formation and fibrin cross-linkage time, slower
      clot formation, decreased platelet function, and clot rigidity. AGK2 treatment
      was associated with dramatic improvements in fibrin cross-linkage and clot
      formation times, without a significant impact on the clot initiation parameters
      or platelet function. Additionally, AGK2 significantly attenuated the bone marrow
      atrophy (58.3+/-6.5 vs 30.0+/-8.2%, p=0.0262). CONCLUSION: Selective inhibition
      of SIRT2 significantly improves survival, and attenuates sepsis-associated
      "cytokine storm", coagulopathy, and bone marrow atrophy in a mouse model of
      lethal septic shock.

PMID- 26299771
TI  - Mechanical Strain Promotes Osteogenesis of BMSCs from Ovariectomized Rats via the
      ERK1/2 but not p38 or JNK-MAPK Signaling Pathways.
AB  - Osteoporosis has become a world-wide health problem. As a promising intervention,
      mechanical strain is considered to be an important factor in bone remodeling.
      However, the underlying mechanisms are still not clarified clearly. In the
      present study, we aim to investigate the possible mechanism by which mechanical
      stimulation induces osteogenic differentiation of bone mesenchymal stem cells
      (BMSCs) from ovariectomized rats (OVX BMSCs). The results demonstrated that
      intermittent mechanical strain (IMS) promoted osteogenic differentiation of OVX
      BMSCs by activating Runt-related transcription factor 2 (Runx2). When the
      extracellular regulated kinase1/2-mitogen activated protein kinases (ERK1/2-MAPK)
      signaling pathway was blocked, the osteogenenic effects of IMS were diminished;
      while blocking of the p38-MAPK signaling pathway had little effect on subsequent
      osteogenic events. In addition, the phosphorylation level of JNK was not affected
      by IMS. Our results indicated that strain-induced osteogenic differentiation of
      OVX BMSCs may take effect via ERK1/2-MAPK not p38 or c-Jun N-terminal (JNK)-MAPK
      signaling pathway. These findings may have implications for physical treatment of
      osteoporosis in vitro. 

PMID- 26299772
TI  - Semen Quality, Hormonal Levels, and Androgen Receptor Gene Polymorphisms in a
      Population of Young Male Volunteers from Two Different Regions of Poland.
AB  - BACKGROUND: The population of healthy Polish men has not been frequently and
      systematically investigated for fertility status. The aim of this study was to
      assess the quality of semen in a randomly recruited population of young males.
      The most important task was to find a relationship between semen parameters, sex
      hormones, and AR gene polymorphism. MATERIAL AND METHODS: Semen and blood samples
      from young men from the Poznan (n=113) and Lublin regions (n=89) were collected
      for semen analysis, assessment of hormonal concentrations, and calculation of the
      CAG and GGN repeats of the AR gene. RESULTS: Statistical comparisons of the
      hormones and circulating proteins and the seminological parameters revealed
      significant differences between the regional groups of males studied. Among the
      correlations found, we emphasize the positive relationship between inhibin B
      levels and both the number of spermatozoa per ml (R=0.37; p=0.0001) and the total
      sperm concentration (R=0.40; p=0.00003). Positive correlations between IGF1 and
      sperm morphology was also found (R=0.40; p=0.000004). The mean number of CAG
      repeats in our tested groups was 21.93+/-2.79, in a range from 16 to 31. The mean
      number of GGN repeats was 23.2+/-1.66 and ranged from 16 to 29. Numerous
      significant correlations were found between CAG or GGN repeats and blood hormones
      or circulating proteins and semen parameters; however, Spearman's rank
      correlations revealed rather weak coefficients. CONCLUSIONS: This report
      attempted to determine the quality of semen samples and sex hormones in a
      population of Polish young men. The results were found to be similar to data
      obtained in Scandinavia. The calculated means and range of CAG or GGN repeats of
      the AR gene in Polish males were similar to West European epidemiological data.

PMID- 26299773
TI  - A Simple Laparoscopic Procedure to Restore a Normal Vaginal Length After
      Colpohysterectomy With Large Upper Colpectomy for Cervical and/or Vaginal
      Neoplasia.
AB  - Colpohysterectomy is sometimes associated with a large upper colpectomy resulting
      in a shortened vagina, potentially impacting sexual function. We report on a
      preliminary experience of a laparoscopic colpoplasty to restore a normal vaginal
      length. Patients with shortened vaginas after a laparoscopic colpohysterectomy
      were considered for a laparoscopic modified Davydov's procedure to create a new
      vaginal vault using the peritoneum of the rectum and bladder. From 2010 to 2014,
      8 patients were offered this procedure, after informed preoperative consent.
      Indications were 2 extensive recurrent vaginal intraepithelial neoplasias grade 3
      and 6 radical hysterectomies for cervical cancer. Mean vaginal length before
      surgery was 3.8 cm (standard deviation, 1.6). Median operative time was 50
      minutes (range, 45-90). Blood loss was minimal (50-100 mL). No perioperative
      complications occurred. Median vaginal length at discharge was 11.3 cm (range, 9
      13). Sexual intercourse could be resumed around 10 weeks after surgery. At a
      median follow-up of 33.8 months (range, 2.4-51.3), 6 patients remained sexually
      active but 2 had stopped. Although this experience is small, this laparoscopic
      modified Davydov's procedure seems to be an effective procedure, adaptable to
      each patient's anatomy. If the initial postoperative regular self-dilatation is
      carefully observed, vaginal patency is durably restored and enables normal sexual
      function. 

PMID- 26299774
TI  - Investigation on preparation and performance of spinel LiNi0.5Mn1.5O4 with
      different microstructures for lithium-ion batteries.
AB  - The high voltage spinel LiNi0.5Mn1.5O4 is a promising cathode material in next
      generation of lithium ion batteries. In this study, LiNi0.5Mn1.5O4 with various
      particle microstructures are prepared by controlling the microstructures of
      precursors. LiNi0.5Mn1.5O4 spinel samples with solid, hollow and hierarchical
      microstructures are prepared with solid MnCO3, hollow MnO2 and hierarchical Mn2O3
      as precursor, respectively. The homemade spinel materials are investigated and
      the results show that the content of Mn(3+) and impurity phase differ much in
      these three spinel samples obtained under the same calcining and annealing
      conditions. It is revealed for the first time that an inhomogeneous migration of
      atoms may introduce Mn(3+) and impurity phase in the spinel. The hierarchical
      microstructure with the primary particles interconnected is optimal for electrode
      materials because this microstructure has a higher conductivity between the
      interconnected primary particles and appropriate specific surface area.
      LiNi0.5Mn1.5O4 in this microstructure has the best rate capability and also the
      best long-term cycling stability. 

PMID- 26299775
TI  - Effect of Reagent Vibrational Excitation on the Dynamics of F + H2(v = 1, j = 0) 
      > HF(v', j') + H Reaction.
AB  - The reaction of fluorine atom with vibrationally excited H2 at v = 1 has been
      studied using a high resolution crossed molecular beam apparatus at collision
      energies of 0.52 and 0.90 kcal/mol. Product HF rotational state-resolved
      differential cross sections (DCSs) were measured at v' = 2, 3, 4 levels. The
      product angular distributions are predominantly backward scattered except for a
      small forward signal of HF(v' = 4) at 0.90 kcal/mol. At the collision energy of
      0.52 kcal/mol, the forward scattering peak of the HF(v' = 2) product, which
      arises in F + H2(v = 0) reaction from the Feshbach resonances, disappears in F +
      H2(v = 1) reaction. Oscillatory structures do not appear in the backward
      direction of the scattering as the collision energy increases from 0.4 to 2.0
      kcal/mol, indicating there are no explicit reaction resonances in the F + H2(v =
      1, j = 0) -> HF + H reaction in the studied energy range. Quantum dynamics
      calculations on a highly accurate potential energy surface are in good agreement
      with the experimental results and reveal that the reaction occurs via likely a
      direct abstraction mechanism, not via long-lived reactive resonances. 

PMID- 26299777
TI  - WITHDRAWN: Gonadotrophin therapy for ovulation induction in subfertility
      associated with polycystic ovary syndrome.

PMID- 26299778
TI  - WITHDRAWN: Recombinant FSH versus urinary gonadotrophins or recombinant FSH for
      ovulation induction in subfertility associated with polycystic ovary syndrome.

PMID- 26299780
TI  - Diluvian Clustering: A Fast, Effective Algorithm for Clustering Compositional and
      Other Data.
AB  - Diluvian Clustering is an unsupervised grid-based clustering algorithm well
      suited to interpreting large sets of noisy compositional data. The algorithm is
      notable for its ability to identify clusters that are either compact or diffuse
      and clusters that have either a large number or a small number of members.
      Diluvian Clustering is fundamentally different from most algorithms previously
      applied to cluster compositional data in that its implementation does not depend
      upon a metric. The algorithm reduces in two-dimensions to a case for which there
      is an intuitive, real-world parallel. Furthermore, the algorithm has few tunable
      parameters and these parameters have intuitive interpretations. By eliminating
      the dependence on an explicit metric, it is possible to derive reasonable
      clusters with disparate variances like those in real-world compositional data
      sets. The algorithm is computationally efficient. While the worst case scales as
      O(N2) most cases are closer to O(N) where N is the number of discrete data
      points. On a mid-range 2014 vintage computer, a typical 20,000 particle, 30
      element data set can be clustered in a fraction of a second.

PMID- 26299779
TI  - Preconditioning Human Cardiac Stem Cells with an HO-1 Inducer Exerts Beneficial
      Effects After Cell Transplantation in the Infarcted Murine Heart.
AB  - The regenerative potential of c-kit(+) cardiac stem cells (CSCs) is severely
      limited by the poor survival of cells after transplantation in the infarcted
      heart. We have previously demonstrated that preconditioning human CSCs (hCSCs)
      with the heme oxygenase-1 inducer, cobalt protoporphyrin (CoPP), has significant
      cytoprotective effects in vitro. Here, we examined whether preconditioning hCSCs
      with CoPP enhances CSC survival and improves cardiac function after
      transplantation in a model of myocardial infarction induced by a 45-minute
      coronary occlusion and 35-day reperfusion in immunodeficient mice. At 30 minutes
      of reperfusion, CoPP-preconditioned hCSCs(GFP+), hCSCs(GFP+), or medium were
      injected into the border zone. Quantitative analysis with real-time qPCR for the
      expression of the human-specific gene HLA revealed that the number of survived
      hCSCs was significantly greater in the preconditioned-hCSC group at 24 hours and
      7 and 35 days compared with the hCSC group. Coimmunostaining of tissue sections
      for both green fluorescent protein (GFP) and human nuclear antigen further
      confirmed greater hCSC numbers at 35 days in the preconditioned-hCSC group. At 35
      days, compared with the hCSC group, the preconditioned-hCSC group exhibited
      increased positive and negative left ventricular (LV) dP/dt, end-systolic
      elastance, and anterior wall/apical strain rate (although ejection fraction was
      similar), reduced LV remodeling, and increased proliferation of transplanted
      cells and of cells apparently committed to cardiac lineage. In conclusion, CoPP
      preconditioning of hCSCs enhances their survival and/or proliferation, promotes
      greater proliferation of cells expressing cardiac markers, and results in greater
      improvement in LV remodeling and in indices of cardiac function after infarction.

PMID- 26299782
TI  - Ionic Liquids with Weakly Coordinating [M(III)(OR(F))4](-) Anions.
AB  - Ionic liquids (ILs) are defined as salts with melting points below 100  degrees
      C. They attracted much attention in the last two decades due to their unique set
      of properties, including high conductivities, low viscosities, negligible vapor
      pressure, and high electrochemical resistance. ILs are seen as tunable systems,
      of which (also in mixtures) up to 10(19) combinations may exist. These properties
      make ILs interesting candidates for a variety of fundamental to industrial
      applications. Our addition to this field was weakly coordinating, little
      interacting anions, the highly fluorinated aluminates [Al(OR(F))4](-) (R(F) =
      C(CF3)3, C(CH3), (CF3)2, and CH(CF3)2 and later also CH2(CF3)). We have used
      these anions in a broad spectrum of applications, including the stabilization of
      reactive cations, (polymerization) catalysis, and conducting salts for cyclic
      voltammetry or in electrochemical cells. Especially the [Al(Ohfip)4](-) (hfip =
      CH(CF3)2) anions in combination with asymmetric organic cations turned out to be
      very well suited for the synthesis of ILs with very low melting points, some even
      far below 0  degrees C. Also the analogous borates, [B(OR(F))4](-), were shown to
      yield ILs, and currently a plethora of such aluminate and borate ILs have been
      synthesized and thoroughly investigated. In many aspects, at least the
      [Al(Ohfip)4](-) ILs present almost ideally noninteracting prototype ILs with
      (nearly) isotropic but weak and flat Coulomb potential. Consequently, their
      overall interionic interactions are significantly reduced compared with other
      classes of ILs, resulting in an extraordinarily low degree, or (for short cation
      chain lengths below six) even complete absence of ion pairing. From thorough
      analysis of the principles governing the physical properties of this highly
      fluorinated IL class with minimized interactions, we were able to learn basic
      principles that could be extended, for example, to the prediction of the
      principal properties of a wide variety of typical ILs. In this Account, we give a
      comprehensive review of their syntheses, thermal and toxicological behavior,
      physical as well as dynamic properties, and use in electrochemical applications.
      We delineate advantages and limitations of the [M(III)(OR(F))4](-) ILs developed
      in our lab and give an outlook on those fields, in which there is still a lack of
      knowledge. 

PMID- 26299781
TI  - Organic acids from root exudates of banana help root colonization of PGPR strain
      Bacillus amyloliquefaciens NJN-6.
AB  - The successful colonization of plant growth promoting rhizobacteria (PGPR) in the
      rhizosphere is an initial and compulsory step in the protection of plants from
      soil-borne pathogens. Therefore, it is necessary to evaluate the role of root
      exudates in the colonization of PGPR. Banana root exudates were analyzed by high
      pressure liquid chromatography (HPLC) which revealed exudates contained several
      organic acids (OAs) including oxalic, malic and fumaric acid. The chemotactic
      response and biofilm formation of Bacillus amyloliquefaciens NJN-6 were
      investigated in response to OA's found in banana root exudates. Furthermore, the
      transcriptional levels of genes involved in biofilm formation, yqxM and epsD,
      were evaluated in response to OAs via quantitative reverse transcriptase
      polymerase chain reaction (qRT-PCR). Results suggested that root exudates
      containing the OAs both induced the chemotaxis and biofilm formation in NJN-6. In
      fact, the strongest chemotactic and biofilm response was found when 50 MUM of OAs
      were applied. More specifically, malic acid showed the greatest chemotactic
      response whereas fumaric acid significantly induced biofilm formation by a 20.7
      27.3% increase and therefore biofilm formation genes expression. The results
      showed banana root exudates, in particular the OAs released, play a crucial role
      in attracting and initiating PGPR colonization on the host roots. 

PMID- 26299783
TI  - Altered folate metabolism modifies cell proliferation and progesterone secretion
      in human placental choriocarcinoma JEG-3 cells.
AB  - Folate is an essential B vitamin required for de novo purine and thymidylate
      synthesis, and for the remethylation of homocysteine to form methionine. Folate
      deficiency has been associated with placenta-related pregnancy complications, as
      have SNP in genes of the folate-dependent enzymes, methionine synthase (MTR) and
      methylenetetrahydrofolate dehydrogenase 1 (MTHFD1). We aimed to determine the
      effect of altered folate metabolism on placental cell proliferation, viability
      and invasive capacity and on progesterone and human chorionic gonadotropin (hCG)
      secretion. Human placental choriocarcinoma (JEG-3) cells cultured in low folic
      acid (FA) (2 nM) demonstrated 13% (P<0.001) and 26% (P<0.001) lower
      proliferation, 5.5% (P=0.025) and 7.5% (P=0.004) lower invasion capacity, and 5
      to 7.5% (P=0.004-0.025) lower viability compared with control (20 nM) or
      supplemented (100 nM) cells, respectively. FA concentration had no effect on
      progesterone or hCG secretion. Small interfering RNA (siRNA) knockdown of MTR
      gene and protein expression resulted in 17.7% (P<0.0001) lower proliferation and
      61% (P=0.014) higher progesterone secretion, but had no effect on cell invasion
      and hCG secretion. siRNA knockdown of MTHFD1 gene expression in the absence of
      detectable changes in protein expression resulted in 10.3% (P=0.001) lower cell
      proliferation, but had no effect on cell invasion and progesterone or hCG
      secretion. Our data indicate that impaired folate metabolism can result in lower
      trophoblast proliferation, and could alter viability, invasion capacity and
      progesterone secretion, which may explain in part the observed associations
      between folate and placenta-related complications.

PMID- 26299784
TI  - Surgical management of canine refractory retrobulbar abscesses: six cases.
AB  - OBJECTIVE: To report the clinical presentation, surgical treatment and outcomes
      of dogs with retrobulbar abscesses refractory to intra-oral lancing and
      antibiotics. METHODS: Medical records from January 2006 through September 2014
      were reviewed and dogs with retrobulbar abscesses failing treatment with
      antibiotics and intra-oral lancing were included. Clinicopathologic, imaging and
      surgical details were extracted from the medical records. Referring veterinarians
      and owners were interviewed via telephone for follow-up data. RESULTS: A total of
      six dogs were included in the study. The most common clinical signs were pain
      upon opening of the mouth, exophthalmos and prolapsed nictitans. Computed
      tomography was performed in five dogs, ultrasound in four and magnetic resonance
      imaging in one. Imaging identified an abscess in all dogs, with a suspected
      foreign body in four dogs. Surgical approach was a modified lateral orbitotomy in
      five dogs. No foreign body was identified during surgery in all dog. All dogs
      surviving to discharge did not have recurrence of clinical signs (follow-up time
      range: 27 to 95 months). CLINICAL SIGNIFICANCE: Dogs with retrobulbar abscesses
      refractory to standard therapy can experience long-term resolution of clinical
      signs with surgical treatment, most commonly via a modified lateral orbitotomy.

PMID- 26299785
TI  - Structure and function of Fic proteins.
AB  - Fic proteins are a family of proteins characterized by the presence of a
      conserved FIC domain that is involved in the modification of protein substrates
      by the addition of phosphate-containing compounds, including AMP and other
      nucleoside monophosphates, phosphocholine and phosphate. Fic proteins are
      widespread in bacteria, and various pathogenic species secrete Fic proteins as
      toxins that mediate post-translational modifications of host cell proteins, to
      interfere with cytoskeletal, trafficking, signalling or translation pathways in
      the host cell. In this Review, we discuss the current knowledge of the structure,
      function and regulation of Fic proteins and consider important areas for future
      research. 

PMID- 26299786
TI  - Viral evolution: The history of Lassa virus.

PMID- 26299787
TI  - Remote ischemic preconditioning protects the spinal cord against ischemic insult:
      An experimental study in a porcine model.
AB  - OBJECTIVE: Surgical repair of thoracoabdominal aneurysm jeopardizes the
      vascularization of the spinal cord, and therefore, despite improvement in
      surgical techniques, still carries the risk of paraplegia. This study aimed to
      demonstrate the possible protective effects of remote ischemic preconditioning
      (RIPC) on the preservation of spinal cord function after segmental artery (SA)
      occlusion. METHODS: Twenty piglets were randomized into the RIPC group (n = 10)
      and the control group (n = 10). The RIPC group underwent transient left hind limb
      ischemia before systematic left subclavian artery and SA occlusion at the level
      of the diaphragm. Motor-evoked potential (MEP) monitoring was performed from the
      hind limbs. Afterward, the thoracic and lumbar spinal cords were harvested and
      analyzed. RESULTS: The elevation of the MEP amplitude after RIPC was
      statistically significant, whereas amplitude was consistently decreased in the
      control group. Additionally, the onset latency was significantly shorter after
      RIPC during SA occlusion. The control group reached a 50% decrease of MEP
      amplitude in the right hind limb sooner than did the experimental group.
      CONCLUSIONS: Remote ischemic preconditioning preserves spinal cord function after
      left subclavian artery and SA occlusion, as indicated by the MEP amplitudes.

PMID- 26299788
TI  - "Coming soon to a cath lab near you...".

PMID- 26299789
TI  - Risk Reduction of an Invasive Insect by Targeting Surveillance Efforts with the
      Assistance of a Phenology Model and International Maritime Shipping Routes and
      Schedules.
AB  - Reducing the risk of introduction to North America of the invasive Asian gypsy
      moth (Lymantria dispar asiatica Vnukovskij and L. d. japonica [Motschulsky]) on
      international maritime vessels involves two tactics: (1) vessels that wish to
      arrive in Canada or the United States and have visited any Asian port that is
      subject to regulation during designated times must obtain a predeparture
      inspection certificate from an approved entity; and (2) vessels with a
      certificate may be subjected to an additional inspection upon arrival. A decision
      support tool is described here with which the allocation of inspection resources
      at North American ports can be partitioned among multiple vessels according to
      estimates of the potential onboard Asian gypsy moth population and estimates of
      the onboard larval emergence pattern. The decision support tool assumes that port
      inspection is uniformly imperfect at the Asian ports and that each visit to a
      regulated port has potential for the vessel to be contaminated with gypsy moth
      egg masses. The decision support tool uses a multigenerational phenology model to
      estimate the potential onboard population of egg masses by calculating the
      temporal intersection between the dates of port visits to regulated ports and the
      simulated oviposition pattern in each port. The phenological development of the
      onboard population is simulated each day of the vessel log until the vessel
      arrives at the port being protected from introduction. Multiple independent
      simulations are used to create a probability distribution of the size and timing
      of larval emergence. 

PMID- 26299791
TI  - Implication of sperm chromosomal abnormalities in recurrent abortion and multiple
      implantation failure.
AB  - Currently, some infertility treatment centres provide sperm karyotype analysis,
      although the impact of sperm chromosomal abnormalities on fertility is not yet
      fully understood. Several studies using fluorescence in-situ hybridization (FISH)
      to analyse sperm chromosomal constitution discovered that the incidence of
      aneuploidy is increased in individuals with a history of repeated abortion or
      implantation failure and is even higher in cases of oligoasthenoteratozoospermia
      (OAT), abnormal somatic karyotype or in spermatozoa retrieved directly from the
      testis or epididymis, showing that the application of FISH in these cases may be
      of some benefit for improving the reproductive outcome. This article presents the
      results of clinical trials of FISH analysis on spermatozoa, the medical
      indications for performing this examination, its results in infertile patients
      and the advantages when performing genetic counselling prior to treatment. Also
      discussed is the possibility of applying the latest techniques of genetic
      analysis in these cases and the potential benefits for improving the prognosis of
      male infertility. 

PMID- 26299790
TI  - Role of Extracorporeal Membrane Oxygenation in Aluminum Phosphide Poisoning
      Induced Reversible Myocardial Dysfunction: A Novel Therapeutic Modality.
AB  - BACKGROUND: Aluminum phosphide (AlP) poisoning carries a high rate of mortality
      despite intensive care management, primarily because of refractory myocardial
      depression, resistant hypotension, and severe metabolic acidosis as well as acute
      respiratory distress syndrome. Extracorporeal membrane oxygenation (ECMO) is a
      modified "heart-lung" machine to provide temporary cardiorespiratory support. We
      studied the novel use of ECMO in the management of a subset of patients with AlP
      poisoning. CASE REPORT: In this case series, seven patients with AlP poisoning
      suffering from severe metabolic acidosis and refractory cardiogenic shock with a
      reduced left ventricular ejection fraction (<35%) received ECMO treatment. The
      acidosis and hemodynamic status improved within 6-12 h and 12-24 h, respectively,
      in five patients. Two patients did not survive because of a long delay in
      presentation after ingestion. The majority of the patients developed
      dysrhythmias, ECMO cannulation site bleeding, and thrombocytopenia. Two patients
      required surgical exploration of the femoral artery. At 9 months of follow-up,
      all five surviving patients were doing well, with the near normalization of
      ventricular function. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: We
      have found that timely intervention with ECMO in patients with AlP poisoning
      induced severe metabolic acidosis and refractory cardiogenic shock may lead to a
      significant improvement in overall survival. Therefore, ECMO might be considered
      as a bridge therapy for patients with intractable cardiorespiratory failure
      caused by AlP poisoning who are not responding to conventional treatment. ECMO,
      however, also is associated with significant complication rates, which must be
      incorporated into the risk-benefit analysis while considering treatment options.

PMID- 26299792
TI  - Evolution, ecology and physiology of amphibious killifishes (Cyprinodontiformes).
AB  - The order Cyprinodontiformes contains an exceptional diversity of amphibious
      taxa, including at least 34 species from six families. These cyprinodontiforms
      often inhabit intertidal or ephemeral habitats characterized by low dissolved
      oxygen or otherwise poor water quality, conditions that have been hypothesized to
      drive the evolution of terrestriality. Most of the amphibious species are found
      in the Rivulidae, Nothobranchiidae and Fundulidae. It is currently unclear
      whether the pattern of amphibiousness observed in the Cyprinodontiformes is the
      result of repeated, independent evolutions, or stems from an amphibious common
      ancestor. Amphibious cyprinodontiforms leave water for a variety of reasons: some
      species emerse only briefly, to escape predation or capture prey, while others
      occupy ephemeral habitats by living for months at a time out of water. Fishes
      able to tolerate months of emersion must maintain respiratory gas exchange,
      nitrogen excretion and water and salt balance, but to date knowledge of the
      mechanisms that facilitate homeostasis on land is largely restricted to model
      species. This review synthesizes the available literature describing amphibious
      lifestyles in cyprinodontiforms, compares the behavioural and physiological
      strategies used to exploit the terrestrial environment and suggests directions
      and ideas for future research. 

PMID- 26299793
TI  - A revised model for estimating g-ratio from MRI.
AB  - A key measure of white matter health is the g-ratio, which is defined as the
      ratio between the inner axon radius and the outer, myelinated, axon radius.
      Recent methods have been proposed to measure the g-ratio non-invasively using the
      relationship between two magnetic resonance imaging (MRI) measures. While this
      relationship is intuitive, it predicates on the simplifying assumption that g
      ratio is constant across axons. Here, we extend the model to account for a
      distribution of g-ratio values within an imaging voxel, and evaluate this model
      with quantitative histology from normal and hypomyelinated mouse brains.

PMID- 26299794
TI  - Functional connectivity MRI tracks memory networks after maze learning in
      rodents.
AB  - Learning and memory employs a series of cognitive processes which require the
      coordination of multiple areas across the brain. However in vivo imaging of
      cognitive function has been challenging in rodents. Since these processes involve
      synchronous firing among different brain loci we explored functional connectivity
      imaging with resting-state fMRI. After 5-day training on a hidden platform
      watermaze task, notable signal correlations were seen between the hippocampal CA3
      and other structures, including thalamus, septum and cingulate cortex, compared
      to swim control or naive animals. The connectivity sustained 7 days after
      training and was reorganized toward the cortex, consistent with views of memory
      trace distribution leading to memory consolidation. These data demonstrates that,
      after a cognitive task, altered functional connectivity can be detected in the
      subsequently sedated rodent using in vivo imaging. This approach paves the way to
      understand dynamics of area-dependent distribution processes in animal models of
      cognition.

PMID- 26299795
TI  - Knowing when not to swing: EEG evidence that enhanced perception-action coupling
      underlies baseball batter expertise.
AB  - Given a decision that requires less than half a second for evaluating the
      characteristics of the incoming pitch and generating a motor response, hitting a
      baseball potentially requires unique perception-action coupling to achieve high
      performance. We designed a rapid perceptual decision-making experiment modeled as
      a Go/No-Go task yet tailored to reflect a real scenario confronted by a baseball
      hitter. For groups of experts (Division I baseball players) and novices (non
      players), we recorded electroencephalography (EEG) while they performed the task.
      We analyzed evoked EEG single-trial variability, contingent negative variation
      (CNV), and pre-stimulus alpha power with respect to the expert vs. novice groups.
      We found strong evidence for differences in inhibitory processes between the two
      groups, specifically differential activity in supplementary motor areas (SMA),
      indicative of enhanced inhibitory control in the expert (baseball player) group.
      We also found selective activity in the fusiform gyrus (FG) and orbital gyrus in
      the expert group, suggesting an enhanced perception-action coupling in baseball
      players that differentiates them from matched controls. In sum, our results show
      that EEG correlates of decision formation can be used to identify neural markers
      of high-performance athletes. 

PMID- 26299796
TI  - Functional connectivity indicates differential roles for the intraparietal sulcus
      and the superior parietal lobule in multiple object tracking.
AB  - Attentive tracking requires sustained object-based attention, rather than passive
      vigilance or rapid attentional shifts to brief events. Several theories of
      tracking suggest a mechanism of indexing objects that allows for attentional
      resources to be directed toward the moving targets. Imaging studies have shown
      that cortical areas belonging to the dorsal frontoparietal attention network
      increase BOLD-signal during multiple object tracking (MOT). Among these areas,
      some studies have assigned IPS a particular role in object indexing, but the
      neuroimaging evidence has been sparse. In the present study, we tested
      participants on a continuous version of the MOT task in order to investigate how
      cortical areas engage in functional networks during attentional tracking.
      Specifically, we analyzed the data using eigenvector centrality mapping (ECM)
      analysis, which provides estimates of individual voxels' connectedness with hub
      like parts of the functional network. The results obtained using permutation
      based voxel-wise statistics support the proposed role for the IPS in object
      indexing as this region displayed increased centrality during tracking as well as
      increased functional connectivity with both prefrontal and visual perceptual
      cortices. In contrast, the opposite pattern was observed for the SPL, with
      decreasing centrality, as well as reduced functional connectivity with the visual
      and frontal cortices, in agreement with a hypothesized role for SPL in
      attentional shifts. These findings provide novel evidence that IPS and SPL serve
      different functional roles during MOT, while at the same time being highly
      engaged during tracking as measured by BOLD-signal changes. 

PMID- 26299797
TI  - Investigating the influence of histidine residues on the metal ion binding
      ability of the wheat metallothionein gamma-Ec-1 domain.
AB  - While Zn(II) and Cd(II) have similar geochemical and environmental properties,
      their biological properties are distinctively different as Cd(II) ions have very
      limited metabolic significance and are mostly even toxic, while Zn(II) ions
      belong to the most essential micronutrients. One of the key proteins involved in
      intracellular Zn(II) and Cd(II) binding are metallothioneins (MTs), small
      cysteine-rich proteins ubiquitously found in many different organisms. In the
      past two decades, also MT sequences from diverse species that contain histidine
      residues have been found, and His-metal ion coordination has been shown. It is
      not clear, however, why in some MTs parts of the Cys residues are replaced by
      His, while most other MTs only contain Cys residues for metal ion binding. To
      address this question, we used the gamma-domain of the early-cysteine labeled (Ec
      1) metallothionein from common wheat as a model system because its enclosed
      M2Cys6 cluster represents the smallest metal-thiolate cluster possible with
      divalent metal ions. Based on the known three-dimensional structure of the gamma
      domain we set about to investigate the influence of a single Cys-to-His mutation
      on the structure and metal ion binding abilities of this domain. Combined data
      obtained by mass spectrometry, UV, as well as NMR spectroscopy suggest a
      preference for Zn(II) versus Cd(II) ions in the histidine containing binding
      site. 

PMID- 26299798
TI  - The present state of the art in expression, production and characterization of
      monoclonal antibodies.
AB  - Monoclonal antibodies (MAb's) have become one the most powerful therapeutic and
      diagnostic tools in modern medicine. Some estimates target the worldwide market
      of MAb's on the order of $125 billion in the next four years. Recent advances in
      molecular biology, immunology, and development of robust production platforms
      will drive the development of more MAb's suitable to treat an ever increasing
      number of disease states. This circumstance combined with the fact that many of
      the original antibody therapies from the 1980 s and 1990 s will soon be coming
      off patent will attract a great deal of investment in the development of larger
      industrial facilities to increase monoclonal antibody to meet increasing demand.
      In this review, the present state of the science that underlies the development
      of new antibodies therapies in Chinese hamster ovary cells combined with a
      description of the present challenges facing the industry in terms of the
      limitations of output and compliance with current good manufacturing practices
      and FDA regulations. Also addressed are future challenges to overcome production
      bottlenecks, description of critical quality control attributes particular to
      antibodies, and detailed treatment of scale-up considerations.

PMID- 26299800
TI  - Children's Everyday Lives Shadowed by Stalking: Post separation Stalking
      Narratives of Finnish Children and Women.
AB  - This qualitative study discusses post separation stalking and its implications in
      children's everyday lives. Based on narratives of 13 Finnish children and 20
      women, the research fills a gap in the knowledge regarding the psychosocial,
      emotional, and physical impacts of stalking on children when their mothers are
      stalked by a former partner. It identifies four forms of impact: (a) an
      atmosphere of fear and feelings of insecurity; (b) disguised acts of stalking and
      the father's performance of care, love, and longing; (c) exploitation of children
      in stalking; and (d) physical abuse, acts of violence, and threats of death. The
      findings indicate that stalking severely constrains children's everyday lives and
      strengthens, yet often distorts, the mother-child bond. The study concludes that
      in cases where mothers are stalked, professionals in the social and health
      services, law enforcement, and criminal justice should view the children, too, as
      victims and construct supportive social relationships for women and children
      facing threatening life situations.

PMID- 26299799
TI  - A combination of excimer laser treatment and topical tacrolimus is more effective
      in treating vitiligo than either therapy alone for the initial 6 months, but not
      thereafter.
AB  - BACKGROUND: There are insufficient data on the long-term outcome of a combination
      therapy that comprises phototherapy and topical administration of tacrolimus.
      AIM: To evaluate the clinical efficacy according to the duration of treatment and
      in vitro results of a combination therapy involving topical tacrolimus and an
      excimer laser in the treatment of vitiligo. METHODS: In total, 276 patients with
      nonsegmental vitiligo were treated with an excimer laser twice weekly, or with
      tacrolimus ointment twice daily, or both. The melanin contents and levels of
      melanogenic enzymes were measured in cultured human melanocytes treated with
      tacrolimus and/or excimer laser. RESULTS: After adjusting for potential
      confounders, the combination of tacrolimus plus excimer laser was significantly
      more effective than either tacrolimus or excimer laser alone (P < 0.001 and P <
      0.01, respectively) for the first 6 months. However, this superiority was not
      observed after the initial 6 months of treatment. In vitro, the combination of
      tacrolimus plus excimer laser led to a higher level of melanogenesis than with
      either treatment alone. CONCLUSIONS: A combination treatment with topical
      tacrolimus and an excimer laser may be useful as an induction therapy for up to 6
      months, but continuation of this therapy for > 6 months might not provide a
      better final outcome than monotherapy.

PMID- 26299801
TI  - Palmoplantar keratoses and Bowen's disease in a Vietnam veteran: Could Agent Blue
      be implicated?
AB  - Agent Blue was an arsenical herbicide used extensively in the Vietnam War.
      Arsenic is one of the known causes of acquired palmoplantar keratoderma (PPK).
      The most common manifestation of arsenic exposure in susceptible individuals is
      bilateral palmoplantar hyperkeratosis. We report a 67-year-old man with no known
      prior exposure to arsenic in the USA or family history of PPK who developed
      multiple squamous cell carcinoma in situ (SCCIS) and palmoplantar hyperkeratotic
      lesions beginning 23 years after service in Vietnam. The SCCIS were located on
      the trunk and extremities in both sun-exposed and non-sun-exposed sites and his
      palmoplantar lesions were diagnosed concurrently with his SCCIS. He has continued
      to develop SCCIS since his first visit to our clinic 25 years ago. 

PMID- 26299802
TI  - Reggie-1/Flotillin-2 regulates integrin trafficking and focal adhesion turnover
      via Rab11a.
AB  - Reggies/flotillins are implicated in trafficking of membrane proteins to their
      target sites and in the regulation of the Rab11a-dependent targeted recycling of
      E-cadherin to adherens junctions (AJs). Here we demonstrate a function of reggies
      in focal adhesion (FA) formation and alpha5- and beta1-integrin recycling to FAs.
      Downregulation of reggie-1 in HeLa and A431 cells by siRNA and shRNA increased
      the number of FAs, impaired their distribution and modified FA turnover. This was
      coupled to enhanced focal adhesion kinase (FAK) and Rac1 signaling and gain in
      plasma membrane motility. Wild type and constitutively-active (CA) Rab11a rescued
      the phenotype (normal number of FAs) whereas dominant-negative (DN) Rab11a
      mimicked the loss-of-reggie phenotype in control cells. That reggie-1 affects
      integrin trafficking emerged from the faster loss of internalized antibody
      labeled beta1-integrin in reggie-deficient cells. Moreover, live imaging using
      TIRF microscopy revealed vesicles containing reggie-1 and alpha5- or beta1
      integrin, trafficking close to the substrate-near membrane and making kiss-and
      run contacts with FAs. Thus, reggie-1 in interaction with Rab11a controls Rac1
      and FAK activation and coordinates the targeted recycling of alpha5- and beta1
      integrins to FAs to regulate FA formation and membrane dynamics. 

PMID- 26299803
TI  - A long noncoding RNA AB073614 promotes tumorigenesis and predicts poor prognosis
      in ovarian cancer.
AB  - Long noncoding RNA (lncRNA) profiles in ovarian cancer (OC) remain largely
      unknown. In the present study, we screened AB073614 as a new candidate lncRNA
      which promotes development of OC, in two independent datasets (GSE18521 and
      GSE38666) from the Gene Expression Omnibus (GEO). The level of AB073614 was then
      detected in 75 paired OC tissues and adjacent normal tissues by qRT-PCR. Results
      showed that AB073614 expression was significantly up-regulated in 85.3% (64/75)
      cancerous tissues compared with normal counterparts (P < 0.01). Further, the 5
      year overall survival (OS) in OC patients with high expression of AB073614 was
      inferior to that with low expression (17.2 months vs 30.0 months, P = 0.0025). To
      investigate the functional role of AB073614, AB073614 siRNA was transfected into
      OC cell lines. Knockdown of AB073614 expression significantly inhibited cell
      proliferation and invasion, resulted in cell arrest in G1 phase of cell cycle and
      a dramatic increase of apoptosis, both in HO-8910 and OVCAR3 cells. In vivo
      experiment also revealed that knockdown AB073614 inhibited OVCAR3 cells
      proliferation. Finally, western blot assays indicated that lncRNA AB073614 may
      exert its function by targeting ERK1/2 and AKT-mediated signaling pathway. In
      conclusion, our study suggests that lncRNA AB073614 acts as a functional oncogene
      in OC development. 

PMID- 26299804
TI  - Suppression of beta-catenin/TCF transcriptional activity and colon tumor cell
      growth by dual inhibition of PDE5 and 10.
AB  - Previous studies suggest the anti-inflammatory drug, sulindac inhibits
      tumorigenesis by a COX independent mechanism involving cGMP PDE inhibition. Here
      we report that the cGMP PDE isozymes, PDE5 and 10, are elevated in colon tumor
      cells compared with normal colonocytes, and that inhibitors and siRNAs can
      selectively suppress colon tumor cell growth. Combined treatment with inhibitors
      or dual knockdown suppresses tumor cell growth to a greater extent than
      inhibition from either isozyme alone. A novel sulindac derivative, ADT-094 was
      designed to lack COX-1/-2 inhibitory activity but have improved potency to
      inhibit PDE5 and 10. ADT-094 displayed >500 fold higher potency to inhibit colon
      tumor cell growth compared with sulindac by activating cGMP/PKG signaling to
      suppress proliferation and induce apoptosis. Combined inhibition of PDE5 and 10
      by treatment with ADT-094, PDE isozyme-selective inhibitors, or by siRNA
      knockdown also suppresses beta-catenin, TCF transcriptional activity, and the
      levels of downstream targets, cyclin D1 and survivin. These results suggest that
      dual inhibition of PDE5 and 10 represents novel strategy for developing potent
      and selective anticancer drugs. 

PMID- 26299807
TI  - The effects of negative and positive mood induction on eating behaviour: A meta
      analysis of laboratory studies in the healthy population and eating and weight
      disorders.
AB  - OBJECTIVE: The aim of this study was to conduct a meta-analysis to quantify the
      effect of induced negative and positive mood on meal consumption in healthy
      participants and patients with eating and weight disorders. METHOD: The search
      term "MOOD" was combined with the following keywords: "TEST MEAL" or "LABORATORY
      FEEDING" or "LABORATORY MEAL" or "TASTE TEST" or "TASTE TASK" to identify the
      relevant studies. RESULTS: Thirty-three studies were selected, including 2491
      participants. Two meta-analyses compared negative mood or positive mood with
      neutral mood. Induced negative mood was significantly associated with greater
      food intake, especially in restrained eaters and binge eaters. Positive mood was
      also associated with greater caloric intake across groups. CONCLUSION: These
      findings support the causal relationship between negative mood and greater food
      intake, especially in restrained eaters and binge eaters. Preliminary evidence
      indicates that strategies to improve positive mood might be of benefit for people
      with anorexia nervosa and bulimia nervosa, although the size of the effect across
      a single meal is small.

PMID- 26299805
TI  - Similar but different: distinct roles for KRAS and BRAF oncogenes in colorectal
      cancer development and therapy resistance.
AB  - Colorectal cancer (CRC) is characterized by recurrent mutations deregulating key
      cell signaling cascades and providing the cancer cells with novel functional
      traits. Among the most frequent mutations in CRC are gain-of-function missense
      mutations in KRAS and BRAF. Oncogenic activation of KRAS and BRAF is mutually
      exclusive and occurs in approximately 40% and 10% of all CRCs, respectively. Here
      we summarize genetic alterations currently described in the literature and
      databases, indicating overlapping but also specific co-occurrences with either
      mutated BRAF or KRAS. We describe common and potentially specific biological
      functions of KRAS and BRAF oncoproteins in the intestinal epithelial cells and
      during initiation and progression of CRC. We discuss signal transduction
      networks, highlighting individual functions of oncogenic KRAS and BRAF in terms
      of feedback loops and their impact on treatment outcome. Finally, we give an
      update on current strategies of targeted therapeutic intervention in oncogenic
      RAS-RAF signaling networks for the treatment of metastatic CRC and outline future
      directions. 

PMID- 26299806
TI  - Fisetin, a phytochemical, potentiates sorafenib-induced apoptosis and abrogates
      tumor growth in athymic nude mice implanted with BRAF-mutated melanoma cells.
AB  - Melanoma is the most deadly form of cutaneous malignancy, and its incidence rates
      are rising worldwide. In melanoma, constitutive activation of the BRAF/MEK/ERK
      (MAPK) and PI3K/AKT/mTOR (PI3K) signaling pathways plays a pivotal role in cell
      proliferation, survival and tumorigenesis. A combination of compounds that lead
      to an optimal blockade of these critical signaling pathways may provide an
      effective strategy for prevention and treatment of melanoma. The phytochemical
      fisetin is known to possess anti-proliferative and pro-apoptotic activities. We
      found that fisetin treatment inhibited PI3K signaling pathway in melanoma cells.
      Therefore, we investigated the effect of fisetin and sorafenib (an RAF inhibitor)
      alone and in combination on cell proliferation, apoptosis and tumor growth.
      Combination treatment (fisetin + sorafenib) more effectively reduced the growth
      of BRAF-mutated human melanoma cells at lower doses when compared to individual
      agents. In addition, combination treatment resulted in enhanced (i) apoptosis,
      (ii) cleavage of caspase-3 and PARP, (iii) expression of Bax and Bak, (iv)
      inhibition of Bcl2 and Mcl-1, and (v) inhibition of expression of PI3K,
      phosphorylation of MEK1/2, ERK1/2, AKT and mTOR. In athymic nude mice
      subcutaneously implanted with melanoma cells (A375 and SK-MEL-28), we found that
      combination therapy resulted in greater reduction of tumor growth when compared
      to individual agents. Furthermore, combination therapy was more effective than
      monotherapy in: (i) inhibition of proliferation and angiogenesis, (ii) induction
      of apoptosis, and (iii) inhibition of the MAPK and PI3K pathways in xenograft
      tumors. These data suggest that simultaneous inhibition of both these signaling
      pathways using combination of fisetin and sorafenib may serve as a therapeutic
      option for the management of melanoma. 

PMID- 26299808
TI  - Repetition and variation in motor practice: A review of neural correlates.
AB  - Random practice results in more effective motor learning than either constant or
      blocked practice. Recent studies have investigated the effects of practice
      schedules at the neurophysiological level. This study aims to conduct a
      literature review of the following issues: (a) the differential involvement of
      premotor areas, the primary motor cortex, the dorsolateral prefrontal cortex and
      the posterior parietal cortex in different types of practice; (b) changes in the
      participation of these areas throughout practice; and (c) the degree of support
      that current neurophysiological findings offer to strengthen the behavioral
      proposition that distinct cognitive processes are generated by different practice
      schedules. Data from 10 studies that investigated associations between practice
      structures and neurobiological substrates were analyzed. The participation of the
      indicated areas was found to depend on practice structure and varied during the
      learning process. Greater cognitive engagement was associated with random
      practice. In conclusion, distinct neural processes are engendered by different
      practice conditions. The integration of behavioral and neurophysiological
      findings promotes a more comprehensive view of the phenomenon. 

PMID- 26299809
TI  - Fractures of the Talus: State of the Art.
AB  - Talus fractures occur rarely but are often associated with complications and
      functional limitations. Urgent reduction of associated dislocations is
      recommended with open reduction and internal fixation of displaced fractures when
      adjacent soft tissue injury permits. Delayed definitive fixation may reduce the
      risks of wound complications and infections. Restoration of articular and axial
      alignment is necessary to optimize ankle and hindfoot function. Despite this,
      posttraumatic arthrosis occurs frequently after talar neck and body fractures,
      especially with comminution of the talar body. Osteonecrosis is reported in up to
      half of talar neck fractures, although many of these injuries will revascularize
      without collapse of the talar dome. Initial fracture displacement and presence of
      open fractures increase the risk of osteonecrosis. Talar process fractures may be
      subtle and easily missed on plain radiographs. Advanced imaging will provide
      detail to facilitate treatment planning. LEVEL OF EVIDENCE: Therapeutic Level V.
      See Instructions for Authors for a complete description of levels of evidence.

PMID- 26299810
TI  - Biomechanical Assessment of Locked Plating for the Fixation of Patella Fractures.
AB  - OBJECTIVE: To analyze the mechanical stability of locked plating in comparison
      with tension-band wiring for the fixation of fractures of the patella. METHODS:
      Biomechanical tests were performed on artificial foam patella specimens comparing
      an angular stable plate and monocortical screws with tension-band wiring. Tests
      were performed under combined tension and bending until failure simulating
      physiological loading of the tibia during walking. RESULTS: Tension-band wiring
      failed at 66% of the failure load of plating (1052 N, P = 0.002) and had 5 times
      larger fracture gap displacements (P = 0.002). CONCLUSIONS: Based on the
      biomechanical advantages, locked plating of the patella may constitute a
      reasonable alternative in the treatment of patella fractures.

PMID- 26299811
TI  - Protein tyrosine phosphatase 1B (PTP1B): A key regulator and therapeutic target
      in liver diseases.
AB  - Phosphorylation of tyrosine residues within proteins, which is controlled by the
      reciprocal action of protein tyrosine kinases and protein tyrosine phosphatases,
      plays a key role in regulating almost all physiological responses. Therefore, it
      comes as no surprise that once the balance of tyrosine phosphorylation is
      disturbed, drastic effects can occur. Protein tyrosine phosphatase 1B (PTP1B), a
      classical non-transmembrane tyrosine phosphatase, is a pivotal regulator and
      promising drug target in type 2 diabetes and obesity. Recently it has received
      renewed attention in liver diseases and represents an intriguing opportunity as a
      drug target by modulating hepatocyte death and survival, hepatic lipogenesis and
      so on. Here, the multiple roles of PTP1B in liver diseases will be presented,
      with respect to liver regeneration, drug-induced liver disease, non-alcoholic
      fatty liver disease (NAFLD) and hepatocellular carcinoma. 

PMID- 26299812
TI  - Epigallocatechin-3-gallate inhibits the invasion of salivary adenoid cystic
      carcinoma cells by reversing the hypermethylation status of the RECK gene.
AB  - Epigallocatechin-3-gallate (EGCG) is an active and major constituent of green
      tea. As a non-nucleoside inhibitor of DNA methylation, EGCG is able to inhibit
      the hypermethylation of newly synthesised DNA, resulting in the reversal of
      hypermethylation and recovery in expression of the silenced genes. Reversion
      inducing cysteine-rich protein with Kazal motifs (RECK) is a novel tumour
      suppressor gene, which negatively regulates matrix metalloproteinases, and
      inhibits tumour invasion, angiogenesis and metastasis. The present study aimed to
      examine the effects of EGCG on the methylation status of the RECK gene and tumour
      invasion in a salivary adenoid cystic carcinoma (SACC) cell line in vitro. Marked
      levels of methylated and weak levels of unmethylated RECK promoter were detected
      in the SACC83 cells, which was determined using methylation-specific polymerase
      chain reaction (PCR). In addition, the treatment of SACC83 cells with EGCG
      partially reversed the hypermethylation status of the RECK gene. Western blot
      analysis and reverse transcription-PCR demonstrated that EGCG significantly
      enhanced the protein and mRNA expression levels of RECK, and significantly
      reduced the invasive ability of the SACC83 cells, as determined using a Transwell
      assay. These results suggested that EGCG possesses novel anti-metastatic
      therapeutic potential for the treatment of SACC.

PMID- 26299813
TI  - Biologically inspired non-heme iron-catalysts for asymmetric epoxidation; design
      principles and perspectives.
AB  - Iron coordination complexes with nitrogen and oxygen donor ligands have long
      since been known to react with peroxides producing powerful oxidizing species.
      These compounds can be regarded as simple structural and functional models of the
      active sites of non-heme iron dependent oxygenases. Research efforts during the
      last decade have uncovered basic principles and structural coordination chemistry
      motifs that permit us to control the chemistry that evolves when these iron
      complexes react with peroxides, in order to provide powerful metal-based, but at
      the same time selective, oxidising agents. Oxidation methodologies with synthetic
      value are currently emerging from this approach. The current review focuses on
      asymmetric epoxidation, a reaction which has large value in synthesis, and where
      iron/H2O2 based methodologies may represent not only a sustainable choice, but
      may also expand the scope of state-of-the-art oxidation methods. Basic principles
      that underlay catalyst design as well as H2O2 activation are discussed, whilst
      limitations and future perspectives are also reviewed. 

PMID- 26299814
TI  - Nutritional, amylolytic enzymes inhibition and antioxidant properties of bread
      incorporated with Stevia rebaudiana.
AB  - Wheat bread with sucrose content replaced with different levels of stevia extract
      was compared with traditional wheat bread. The ability to reduce glucose intake
      was highlighted by performing enzymatic assays using alpha-amylase and alpha
      glucosidase. Antioxidant activity was measured by determining the scavenging
      effect on alpha,alpha-diphenyl-beta-picrylhydrazyl radical. In comparison with
      the control, the bread with stevia extract was softer and had lower microbial
      growth during the shelf-life study. The sensory test showed that the substitution
      of 50% stevia extract was more acceptable when comparing with all the quality
      characteristics. Regarding the nutritional contribution, the content of dietary
      fiber and digestible carbohydrates in the bread with stevia extract was higher
      and lower respectively, so caloric intake was significantly reduced. The results
      showed that the biological properties of Stevia rebaudiana extract were retained
      after the bread making process and that the proposed bread could be suitable as
      functional food in human nutrition. 

PMID- 26299815
TI  - Detection of Patients at High Risk of Medication Errors: Development and
      Validation of an Algorithm.
AB  - Medication errors (MEs) are preventable and can result in patient harm and
      increased expenses in the healthcare system in terms of hospitalization,
      prolonged hospitalizations and even death. We aimed to develop a screening tool
      to detect acutely admitted patients at low or high risk of MEs comprised by items
      found by literature search and the use of theoretical weighting. Predictive
      variables used for the development of the risk score were found by the literature
      search. Three retrospective patient populations and one prospective pilot
      population were used for modelling. The final risk score was evaluated for
      precision by the use of sensitivity, specificity and area under the ROC (receiver
      operating characteristic) curves. The variables used in the final risk score were
      reduced renal function, the total number of drugs and the risk of individual
      drugs to cause harm and drug-drug interactions. We found a risk score in the
      prospective population with an area under the ROC curve of 0.76. The final risk
      score was found to be quite robust as it showed an area under the ROC curve of
      0.87 in a recent patient population, 0.74 in a population of internal medicine
      and 0.66 in an orthopaedic population. We developed a simple and robust score,
      MERIS, with the ability to detect patients and divide them according to low and
      high risk of MEs in a general population admitted at acute admissions unit. The
      accuracy of the risk score was at least as good as other models reported using
      multiple regression analysis. 

PMID- 26299816
TI  - Redox activity of melanin from the ink sac of Sepia officinalis by means of
      colorimetric oxidative assay.
AB  - The redox properties of natural extract from cuttlefish ink sac (Sepia
      officinalis) and synthetic melanin used as a biomimetic in melanin structural
      investigation were determined by comparison of this phenol-based heterogeneous
      pigment with gallic acid used as a standard in Folin-Ciocalteu colorimetric assay
      widely employed for characterisation of oxidative properties of biomaterials.
      Reactivity of sepia melanin reported here is much higher than previously
      indicated and this protocol should allow the redox characterisation of all
      melanins irrespective of their origin and composition. 

PMID- 26299817
TI  - An in vitro study on the antioxidant capacity of usnic acid on human erythrocytes
      and molecular models of its membrane.
AB  - Usnic acid (UA) has been associated with chronic diseases through its antioxidant
      action. Its main target is the cell membrane; however, its effect on that of
      human erythrocytes has been scarcely investigated. To gain insight into the
      molecular mechanisms of the interaction between UA and cell membranes human
      erythrocytes and molecular models of its membrane have been utilized.
      Dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine
      (DMPE) were chosen as representative of phospholipid classes located in the outer
      and inner monolayers of the erythrocyte membrane, respectively. Results by X-ray
      diffraction showed that UA produced structural perturbations on DMPC and DMPE
      bilayers. DSC studies have indicated that thermotropic behavior of DMPE was most
      strongly distorted by UA than DMPC, whereas the latter is mainly affected on the
      pretransition. Scanning electron (SEM) and defocusing microscopy (DM) showed that
      UA induced alterations to erythrocytes from the normal discoid shape to
      echinocytes. These results imply that UA molecules were located in the outer
      monolayer of the erythrocyte membrane. Results of its antioxidant properties
      showed that UA neutralized the oxidative capacity of HClO on DMPC and DMPE
      bilayers; SEM, DM and hemolysis assays demonstrated the protective effect of UA
      against the deleterious oxidant effects of HClO upon human erythrocytes. 

PMID- 26299818
TI  - Bacterial genotoxins: The long journey to the nucleus of mammalian cells.
AB  - Bacterial protein genotoxins target the DNA of eukaryotic cells, causing DNA
      single and double strand breaks. The final outcome of the intoxication is
      induction of DNA damage responses and activation of DNA repair pathways. When the
      damage is beyond repair, the target cell either undergoes apoptosis or enters a
      permanent quiescent stage, known as cellular senescence. In certain instances,
      intoxicated cells can survive and proliferate. This event leads to accumulation
      of genomic instability and acquisition of malignant traits, underlining the
      carcinogenic potential of these toxins. The toxicity is dependent on the toxins'
      internalization and trafficking from the extracellular environment to the
      nucleus, and requires a complex interaction with several cellular membrane
      compartments: the plasma membrane, the endosomes, the trans Golgi network and the
      endoplasmic reticulum, and finally the nucleus. This review will discuss the
      current knowledge of the bacterial genotoxins internalization pathways and will
      highlight the issues that still remain unanswered. This article is part of a
      Special Issue entitled: Pore-Forming Toxins edited by Mauro Dalla Serra and
      Franco Gambale. 

PMID- 26299819
TI  - Chlorpromazine-induced changes in membrane micro-architecture inhibit
      thrombopoiesis in rat megakaryocytes.
AB  - Chlorpromazine often causes severe and persistent thrombocytopenia. Several
      clinical studies have suggested the presence of an as-yet-unknown mechanism in
      this drug-induced thrombocytopenia, by which the platelet production from
      megakaryocytes may directly be affected. As we previously demonstrated in rat
      peritoneal mast cells or adipocytes, chlorpromazine is amphiphilic and
      preferentially partitioned into the lipid bilayers of the plasma membrane.
      Therefore, it can induce some structural changes in the megakaryocyte membrane
      surface and thus affect the process of thrombopoiesis. In the present study,
      employing the standard patch-clamp whole-cell recording technique, we examined
      the effects of chlorpromazine on the membrane capacitance and Kv1.3-channel
      currents in rat megakaryocytes. By electron microscopic imaging of the cellular
      surface, we also examined the effects of chlorpromazine on the membrane micro
      architecture of megakaryocytes. Chlorpromazine markedly decreased the membrane
      capacitance of megakaryocytes, indicating the decreased number of invaginated
      plasma membranes, which was not detected by the fluorescent imaging techniques.
      As shown by electron microscopy, chlorpromazine actually changed the membrane
      micro-architecture of megakaryocytes, and was likely to halt the process of pro
      platelet formation in the cells. This drug persistently decreased the membrane
      capacitance and almost totally and irreversibly inhibited the Kv1.3-channel
      currents in megakaryocytes. This study demonstrated for the first time that
      chlorpromazine is likely to inhibit the process of thrombopoiesis persistently in
      megakaryocytes, as detected by the long-lasting decrease in the membrane
      capacitance and the irreversible suppression of the Kv1.3-channel currents.
      Chlorpromazine-induced changes in the membrane micro-architecture are thought to
      be responsible for its persistent effects. 

PMID- 26299820
TI  - Hemolysin of uropathogenic Escherichia coli: A cloak or a dagger?
AB  - Hemolysin from uropathogenic Escherichia coli (UPEC) is a hemolytic and cytotoxic
      protein active against a broad range of species and cell types. Expression of
      hemolysin correlates with severity of infection, as up to 78% of UPEC isolates
      from pyelonephritis cases express hemolysin. Despite decades of research on
      hemolysin activity, the mechanism of intoxication and the function of hemolysin
      in UPEC infection remain elusive. Early in vitro research established the role of
      hemolysin as a lytic protein at high doses. It is hypothesized that hemolysin is
      secreted at sublytic doses in vivo and recent research has focused on
      understanding the more subtle effects of hemolysin both in vitro and in elegant
      infection models in vivo, including inoculation by micropuncture of individual
      kidney nephrons. As the field continues to evolve, comparisons of hemolysin
      function in isolates from a range of UTI infections will be important for
      delineating the role of this toxin. This article is part of a Special Issue
      entitled: Pore-Forming Toxins edited by Mauro Dalla Serra and Franco Gambale. 

PMID- 26299821
TI  - Electrodeposition of Pt nanostructures with reproducible SERS activity and
      superhydrophobicity.
AB  - Surface-enhanced Raman scattering (SERS) activity and water wettability are
      important characteristic properties of nanostructured surfaces with respect to
      their practical applications. In the present work, we report a simple one-step
      electrodeposition of nanostructured Pt surfaces. The tree-like Pt nanostructures
      exhibited reproducible SERS activity, and they also showed superhydrophobic
      natures after n-dodecanethiol modification. The growth process of Pt
      nanostructures as a function of deposition charge was monitored using a scanning
      electron microscope, from which the correlation between the structural variation
      of the Pt nanostructures and the SERS activity and wettability was investigated.
      The SERS activity was dependent on the presence of sharp edge sites, whereas the
      wettability was dependent on the apex structures. Well-defined Pt tree
      nanostructures exhibited high, reproducible, and electrochemically stable SERS
      activity. The straightforward fabrication of multi-functional Pt nanostructures
      presented in this work would allow new opportunities for the application of
      nanostructured metal surfaces. 

PMID- 26299822
TI  - A PCR-free fluorescence strategy for detecting telomerase activity via double
      amplification strategy.
AB  - As a universal tumor biomarker, research on the activity and inhibition of
      telomerase is of great importance for cancer diagnosis and therapy. Although the
      telomeric repeat amplification protocol (TRAP) has served as a powerful assay for
      detecting telomerase activity, its application has been significantly limited by
      amplification related errors and time-consuming procedure. To address the
      limitations of PCR-based protocol, a dual amplification fluorescence assay was
      developed for PCR-free detecting telomerase activity. Briefly, we designed an
      arch-structure DNA probe to specifically control strand displacement reaction and
      subsequent enzyme-aided amplification. Telomerase substrate (TS) primer was
      extended by telomerase to form long elongation products which contain several
      TTAGGG repeat units. So, one elongation product can release more than one trigger
      DNA (t-DNA) via strand displacement reaction to realize first amplification.
      Subsequently, t-DNA specifically opened molecular beacon (MB) to restore the
      fluorescence of MB. Meanwhile, t-DNA was recycled by the aid of nicking
      endonuclease to continuously open more and more MBs, leading to a second
      amplification. Owing to the double amplification strategy, the proposed method
      allowed the measurement of telomerase activity in crude cell extracts equivalent
      to 5 HeLa cells and 10 CCRF-CEM cells without PCR amplification. Besides, the
      influence of telomere-binding ligands on the telomerase activity demonstrated
      that the proposed method holds the potential to evaluate the inhibition
      efficiency of telomerase inhibitors. 

PMID- 26299823
TI  - Enhancement of surface plasmon resonance signals using a MIP/GNPs/rGO nano-hybrid
      film for the rapid detection of ractopamine.
AB  - A novel surface plasmon resonance (SPR) sensor that uses molecular imprinted
      polymers (MIPs) coated with gold nanoparticles (GNPs) and reduced graphene oxide
      (rGO) as a sensing nano-hybrid film was developed for detection of ractopamine.
      The MIPs were synthesized by precipitation polymerization and characterized by
      scanning electron microscopy and Scatchard analysis. The GNPs/rGO composite was
      synthesized by a single-step reduction of graphene oxide and HAuCl4 solution. The
      MIP/GNPs/rGO nano-hybrid film was immobilized onto a bare sensor chip and
      exhibited remarkable sensitivity and stability by the "grafting to" method with
      the assistance of ionic liquid (IL) as a binder. The prepared sensor showed class
      specific selectivity for ractopamine (RAC) and its analogs under optimized
      conditions. The novel SPR sensor had a wide linear range over an RAC
      concentration from 20 to 1000 ng/mL with a detection limit of 5 ng/mL (S/N=3).
      The results demonstrated that the MIP/GNPs/rGO nano-hybrid film was suitable as
      the recognition element of the SPR sensorfor rapid screening and detection of
      beta-agonists such as RAC.

PMID- 26299824
TI  - Methods and considerations for the analysis and standardization of assessing
      muscle sympathetic nerve activity in humans.
AB  - The technique of microneurography and the assessment of muscle sympathetic nerve
      activity (MSNA) are used in laboratories throughout the world. The variables used
      to describe MSNA, and the criteria by which these variables are quantified from
      the integrated neurogram, vary among studies and laboratories and, therefore, can
      become confusing to those starting to learn the technique. Therefore, the purpose
      of this educational review is to discuss guidelines and standards for the
      assessment of sympathetic nervous activity through the collection and analysis of
      MSNA. This review will reiterate common practices in the collection of MSNA, but
      will also introduce considerations for the evaluation and physiological inference
      using MSNA. 

PMID- 26299825
TI  - Synthesis of 1,2-benzisoxazole tethered 1,2,3-triazoles that exhibit anticancer
      activity in acute myeloid leukemia cell lines by inhibiting histone deacetylases,
      and inducing p21 and tubulin acetylation.
AB  - 1,2,3-Triazole-based heterocycles have previously been shown to possess
      significant anticancer activity in various tumor models. In the present study, we
      attached a 1,2,3-triazole moiety to the third position of a 1,2-benzisoxazole
      heterocycle via copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) with
      various alkynes and established for the title compounds significant
      antiproliferative effect against human acute myeloid leukemia (AML) cells. Among
      the tested compounds, 3-(4-(4-phenoxyphenyl)-1H-1,2,3-triazol-1
      yl)benzo[d]isoxazole (PTB) was found to be the most potent antiproliferative
      agent with an IC50 of 2 MUM against MV4-11 cells using MTT assay. Notably, PTB
      induced cytotoxicity in MOLM13, MOLM14 and MV4-11 cells with selectivity over
      normal bone marrow cells (C57BL/6). Furthermore, PTB was found to induce
      cytotoxicity by increasing apoptosis of AML cells (MOLM13, MOLM14 and MV4-11) as
      well as sub-G1 cell population and apoptotic cells at submicromolar
      concentrations, as shown by flow cytometry and Annexin-V staining, respectively.
      On the protein level we suggested histone deacetylases (HDACs) as the potential
      protein target of those compounds in silico, and the predicted target was next
      experimentally validated by measuring the variations in the levels of p21, cyclin
      D and acetylation of histone H3 and tubulin. Molecular docking analysis of the
      title compounds with the second deacetylase domain of HDAC6 displayed high degree
      of shape complementarity to the binding site of the enzyme, forming multiple
      molecular interactions in the hydrophobic region as well as a hydrogen bond to
      the phenol side-chain of Tyr-782. Thus, 1,2,3-triazole derivatives appear to
      represent a class of novel, biologically active ligands against histone
      deacetylases which deserve to be further evaluated in their applications in the
      cancer field.

PMID- 26299826
TI  - 1,4-Disubstituted aromatic piperazines with high 5-HT2A/D2 selectivity:
      Quantitative structure-selectivity investigations, docking, synthesis and
      biological evaluation.
AB  - Simultaneous targeting of dopamine D2 and 5-HT2A receptors for the treatment of
      schizophrenia is one key feature of typical and atypical antipsychotics. In most
      of the top-selling antipsychotic drugs like aripiprazole and risperidone, high
      affinity to both receptors can be attributed to the presence of 1,4-disubstituted
      aromatic piperazines or piperidines as primary receptor recognition elements.
      Taking advantage of our in-house library of phenylpiperazine-derived dopamine
      receptor ligands and experimental data, we established highly significant CoMFA
      and CoMSIA models for the prediction of 5-HT2A over D2 selectivity. Subsequently,
      the models were applied to identify the selective candidates 55-57 from our newly
      synthesized library of GPCR ligands comprising a pyrazolo[1,5-a]pyridine head
      group and a 1,2,3-triazole based linker unit. The test compound 57 showed
      subnanomolar a Ki value (0.64 nM) for 5-HT2A and more than 10- and 30-fold
      selectivity over the dopamine receptor isoforms D2S and D2L, respectively.

PMID- 26299828
TI  - Nerve reconstruction after sural nerve biopsy with supermicrosurgical fascicular
      turnover flap.

PMID- 26299827
TI  - Discovery of 5-substituted tetrahydronaphthalen-2yl-methyl with N-phenyl-N
      (piperidin-4-yl)propionamide derivatives as potent opioid receptor ligands.
AB  - A new series of novel opioid ligands have been designed and synthesized based on
      the 4-anilidopiperidine scaffold containing a 5-substituted tetrahydronaphthalen
      2yl)methyl group with different N-phenyl-N-(piperidin-4-yl)propionamide
      derivatives to study the biological effects of these substituents on MU and delta
      opioid receptor interactions. Recently our group reported novel 4
      anilidopiperidine analogues, in which several aromatic ring-contained amino acids
      were conjugated with N-phenyl-N-(piperidin-4-yl)propionamide and examined their
      biological activities at the MU and delta opioid receptors. In continuation of
      our efforts in these novel 4-anilidopiperidine analogues, we took a
      peptidomimetic approach in the present design, in which we substituted aromatic
      amino acids with tetrahydronaphthalen-2yl methyl moiety with amino, amide and
      hydroxyl substitutions at the 5th position. In in vitro assays these ligands,
      showed very good binding affinity and highly selective toward the MU opioid
      receptor. Among these, the lead ligand 20 showed excellent binding affinity (2
      nM) and 5000 fold selectivity toward the MU opioid receptor, as well as
      functional selectivity in GPI assays (55.20 +/- 4.30 nM) and weak or no agonist
      activities in MVD assays. Based on the in vitro bioassay results the lead
      compound 20 was chosen for in vivo assessment for efficacy in naive rats after
      intrathecal administration. Compound 20 was not significantly effective in
      alleviating acute pain. This discrepancy between high in vitro binding affinity,
      moderate in vitro activity, and low in vivo activity may reflect differences in
      pharmacodynamics (i.e., engaging signaling pathways) or pharmacokinetics (i.e.,
      metabolic stability). In sum, our data suggest that further optimization of this
      compound 20 is required to enhance in vivo activity.

PMID- 26299829
TI  - [Editorial commentary. Hans Selye Symposium, Budapest, November 2014].

PMID- 26299830
TI  - [Hans Selye, the grandmaster of creativity and originality].
AB  - Hans Selye, the father of the stress concept, was a giant of science of the
      twentieth century. Beyond his best-known work on stress, he also made several
      discoveries on various other fields of experimental medicine. He described and
      characterized various pluricausal diseases. In addition, he made pivotal
      contributions to the broad field of endocrinology, especially to the
      classification of steroids and to our better understanding of their mode of
      action. He developed surgical technics and experimental animal models suitable
      for studying the pathogenesis and prevention of human diseases. Selye was an
      extremely well educated, highly intelligent and disciplined individual, an
      original and creative scientist, an outstanding teacher, a philosopher, a
      prolific author, a fabulous communicator and a gifted organizer successfully
      establishing, developing and managing a major academic research institution, the
      word-famous Institute of Experimental Medicine and Surgery of the University of
      Montreal.

PMID- 26299831
TI  - [Stress and the kynurenine pathway].
AB  - The kynurenine pathway is the main route of tryptophan degradation which gives
      rise to several neuroactive metabolites. Kynurenic acid is an endogenous
      antagonist of excitatory receptors, which proved to be neuroprotective in the
      preclinical settings. Kynurenines have been implicated in the neuroendocrine
      regulatory processes. Stress induces several alterations in the kynurenine
      metabolism and this process may contribute to the development of stress-related
      pathological processes. Irritable bowel disease and gastric ulcer are well-known
      disorders which are related to psychiatric comorbidity and stress. In
      experimental conditions kynurenic acid proved to be beneficial by reducing
      inflammatory processes and normalizing microcirculation in the bowel. Further
      investigations are needed to better understand the relations of stress and the
      kynurenines, with the aim of developing novel therapeutic tools for stress
      related pathologies.

PMID- 26299832
TI  - [Naming and classification of steroids and human stress ulcers. Articles of
      historic significance published by Hans Selye 70 years ago].
AB  - The name of Hans Selye is mostly known worldwide as the discoverer of stress
      reaction. Yet, he made numerous other seminal and clinically relevant
      discoveries. Namely, since he had a focused research on steroid hormones
      originating from the adrenal cortex that play a crucial role in stress response,
      he was the first who introduced about 70 years ago the first classification of
      steroids that is still valid nowadays. This is based on three objective facts:
      (a) the names of steroid groups are identical with their organ of origin (e.g.,
      corticoids from the adrenal cortex, testoids/androgens from the testis); (b)
      chemical structures of the steroids are identical within a group (e.g., all
      corticoids have pregnane nucleus with 21 carbon atoms); and (c) the biological
      effects are homogenous within a group (e.g., all glucocorticoids exert catabolic
      effect, while androgens are anabolic). It should be emphasized that Selye also
      discovered in animal models the pro-inflammmatory effect of mineralocorticoids
      and the anti-inflammatory properties of glucocorticoids, about 8-10 years before
      Nobel Prize was awarded to a physician for the first clinical use of
      adrenocorticotrop hormone and cortisone. Last, but not least, Selye was the first
      who recognized about 70 years ago the occurence of stress ulcers in humans, based
      on clinical reports on the huge increase in the number of perforated gastric anti
      duodenal ulcers during bombings of London in World War II. The subsequent ulcer
      research by Selye's former students and their contemporaries resulted in the
      recognition of anti-duodenal ulcer effect of dopamine, and the central
      gastroprotective actions of thyreotrop releasing hormone and endogenous opioids.
      Thus, Hans Selye made much more contributions to medical science and clinical
      practice than 'just' the discoverer of biologic stress response.

PMID- 26299833
TI  - [Steroids: The physiologic and pharmacologic effects of glucocorticoids].
AB  - Glucocorticoids are widely used in medical practice mainly for suppression of the
      immune system. According to Selye - who named them - the endogenous molecules are
      very important for the adaptation to challenges, stress. They were synthesized in
      the 1940s. Since then numerous data have been published about their production
      (also locally in several organs), transportation (primarily cortisol-binding
      globulin) and receptors (nuclear and non-genomic effects). Although
      glucocorticoids are primarily under the control of the hypothalamo-pituitary
      adrenocortical axis, several other molecules (especially catecholamines) may also
      increase their secretion. Their permissive influences are dominant, thereby they
      are indispensable for the effect of numerous other molecules. Thus,
      glucocorticoids have very diverse influence from metabolism through
      cardiovascular effect to bone-metabolism, affecting even the central nervous
      system. They are also important in metabolic syndrome. Their extensive
      therapeutic usage are limited by side-effects, which could be diminished - among
      others - with concomitant usage of the anabolic dehydroepiandrosterone.

PMID- 26299834
TI  - [Peptic ulcer disease and stress].
AB  - The discovery that Helicobacter pylori infection is the major cause of peptic
      ulcer disease revolutionised our views on the etiology and treatment of the
      disease. This discovery has tempted many experts to conclude that psychological
      factors and, specifically, stress are unimportant. However, Helicobacter pylori
      infection alone does not explain fully the incidence and prevalence of peptic
      ulcer disease. It has been demonstrated that stress can cause peptic ulcer
      disease even in the absence of Helicobacter pylori infection, supporting a
      multicausal model of peptic ulcer etiology. Psychological stress among other risk
      factors can function as a cofactor with Helicobacter pylori infection.

PMID- 26299835
TI  - [Stress and fertility].
AB  - In Western countries, sperm quality and fertility of men significantly worsened.
      Female infertility does not show a better trend either. Subtle defects in the
      reproductive functions can not be explained by the current methods, and
      "unexplained infertility" is becoming a more common diagnosis. Every year 1
      million couples seek expensive and time consuming fertility treatment in the
      world. Deeper understanding of an unhealthy lifestyle and the environmental
      damages may lead to personalized treatments to increase the chance of
      conception.The effects of various stressors on the male and female reproductive
      performance were scientifically substantiated by Selye and coworkers in 1976.
      Cognitive therapy methods can be applied against emotional stressors,
      supplementation by antioxidants against reactive oxygen compounds, and
      administration of vitamins and trace elements, especially when deficiency is
      found, may help before medical intervention on a rational and economical way in
      the fight against infertility.

PMID- 26299836
TI  - [A peculiar man - about Hans Selye, as reflected in his Hungarian connections].
AB  - Hans Selye made a great impact on the Hungarian medical, scientific and public
      life. His first Hungarian publication about the alarm-reaction appeared 1938 in
      the Orvosi Hetilap. His Hungarian relationship was quite extensive after the war
      as he published, gave lectures, and accepted Hungarian students for specialized
      training in his Canadian institute saw. The rich documents in archives about
      Selye are currently being processed and those will surely shed light on Selye's
      life in further details.

PMID- 26299837
TI  - Multi-scale modeling of cell survival and death mediated by the p53 network: a
      systems pharmacology framework.
AB  - The determination of cell fate is a key regulatory process for the development of
      complex organisms that are controlled by distinct genes in mammalian cells. To
      interpret the decision process in a rigorous, analytical framework, we performed
      a multi-scale simulation of cell fate decision mediated by the p53 regulatory
      network in a systems pharmacology framework. The model treats fate determination
      as a gradual response to stress that delays the initiation of apoptosis to give
      the cell an opportunity to survive. The newly proposed two-factor model: DNA-p53
      coupling explains the phenomenon of the existing biological responses to stress
      damage for the p53 regulatory network. In addition, the model also reveals that
      the cell survival rate can be improved by lowering the p53 level in a feedback
      network to increase its robustness for external stimuli. The present work not
      only deepens our understanding of cell fate determination, but also provides a
      theoretical basis for rational drug discovery and development. 

PMID- 26299838
TI  - In response to Melgari et al. "hERG potassium channel inhibition by ivabradine
      requires channel gating".

PMID- 26299839
TI  - Angiotensin II-induced TLR4 mediated abdominal aortic aneurysm in apolipoprotein
      E knockout mice is dependent on STAT3.
AB  - Abdominal Aortic Aneurysm (AAA) is a major cause of mortality and morbidity in
      men over 65 years of age. Male apolipoprotein E knockout (ApoE(-/-)) mice infused
      with angiotensin II (AngII) develop AAA. Although AngII stimulates both JAK/STAT
      and Toll-like receptor 4 (TLR4) signaling pathways, their involvement in AngII
      mediated AAA formation is unclear. Here we used the small molecule STAT3
      inhibitor, S3I-201, the TLR4 inhibitor Eritoran and ApoE(-/-)TLR4(-/-) mice to
      evaluate the interaction between STAT3 and TLR4 signaling in AngII-induced AAA
      formation. ApoE(-/-) mice infused for 28 days with AngII developed AAAs and
      increased STAT3 activation and TLR4 expression. Moreover, AngII increased
      macrophage infiltration and the ratio of M1 (pro-inflammatory)/M2 (healing)
      macrophages in aneurysmal tissue as early as 7-10 days after AngII infusion.
      STAT3 inhibition with S3I-201 decreased the incidence and severity of AngII
      induced AAA formation and decreased MMP activity and the ratio of M1/M2
      macrophages. Furthermore, AngII-mediated AAA formation, MMP secretion, STAT3
      phosphorylation and the ratio of M1/M2 macrophages were markedly decreased in
      ApoE(-/-)TLR4(-/-) mice, and in Eritoran-treated ApoE(-/-) mice. TLR4 and pSTAT3
      levels were also increased in human aneurysmal tissue. These data support a role
      of pSTAT3 in TLR4 dependent AAA formation and possible therapeutic roles for TLR4
      and/or STAT3 inhibition in AAA.

PMID- 26299841
TI  - Evaluating clinically significant changes in health-related quality of life: A
      sample of relatives of patients with severe traumatic brain injury.
AB  - The objective of the study was to investigate change and predictors of change in
      health-related quality of life (HRQoL) in relatives of patients with severe
      traumatic brain injury (TBI) during rehabilitation, and to analyse associations
      between changes in HRQoL and symptoms of anxiety and depression. The Vitality
      (VT), Mental Health (MH), Social Function (SF) and the Role Emotional (RE) scales
      from the Short Form 36, and the anxiety and depression scales from the Symptom
      Checklist-90 - Revised were used. Of the 62 relatives, 24.6% experienced a
      reliable improvement on the VT scale, 53.2% on the MH scale, 27.4% on the SF
      scale and 16.1% on the RE scale. Of the relatives, 24.0% experienced clinically
      significant change (CSC) on the VT scale, 19.6% on the MH scale, 21.6% on the SF
      scale, and 19.2% on the RE scale. Relatives' age and higher patient Glasgow Coma
      Scale score predicted the experience of CSC in RE, and change on the Functional
      Independence Measure in patients predicted CSC on the MH scale. Improvements in
      VT as well as MH were associated with improvement in symptoms of anxiety and
      depression, and improvement in SF was associated with improvement in symptoms of
      depression. About one-fifth of the sample experienced a CSC on one of the four
      HRQoL measures. Relatives experiencing CSC tended to be related to patients who
      showed more improvement during rehabilitation. Improvements in HRQoL were
      associated with improvements in symptoms of anxiety and depression.

PMID- 26299840
TI  - Examining explanations for the link between bullying perpetration and physical
      dating violence perpetration: Do they vary by bullying victimization?
AB  - This short-term longitudinal study examined whether the association between
      bullying perpetration and later physical dating violence perpetration and
      mediators of that association (via anger, depression, anxiety, and social
      status), varied depending on level of bullying victimization. Differences have
      been noted between those who bully but are not victims of bullying, and those who
      are both bullies and victims. These differences may influence dating violence
      risk and the explanations for why bullying leads to dating violence. Data were
      from dating adolescents in three rural counties who completed self-administered
      questionnaires in the fall semester of grades 8-10 and again in the spring
      semester. The sample (N = 2,414) was 44.08% male and 61.31% white. Bullying
      perpetration in the fall semester predicted physical dating violence perpetration
      in the spring semester when there was no bullying victimization, but not when
      there was any bullying victimization. Bullying perpetration was positively
      associated with anger at all levels of bullying victimization and with social
      status when there was no or low amounts of victimization; it was negatively
      associated with social status at high levels of victimization. Bullying
      victimization was positively associated with anger, depression, and anxiety at
      all levels of bullying perpetration. Anger mediated the association between
      bullying perpetration and dating violence, regardless of level of victimization;
      depression, anxiety, and social status did not mediate the association at any
      level of bullying victimization. The findings have implications for dating
      violence prevention efforts and for future research on the link between bullying
      and dating violence.

PMID- 26299842
TI  - Psychophysical and neural correlates of noised-induced tinnitus in animals: Intra
      and inter-auditory and non-auditory brain structure studies.
AB  - Tinnitus, a ringing in the ear or head without an external sound source, is a
      prevalent health problem. It is often associated with a number of limbic
      associated disorders such as anxiety, sleep disturbance, and emotional distress.
      Thus, to investigate tinnitus, it is important to consider both auditory and non
      auditory brain structures. This paper summarizes the psychophysical,
      immunocytochemical and electrophysiological evidence found in rats or hamsters
      with behavioral evidence of tinnitus. Behaviorally, we tested for tinnitus using
      a conditioned suppression/avoidance paradigm, gap detection acoustic reflex
      behavioral paradigm, and our newly developed conditioned licking suppression
      paradigm. Our new tinnitus behavioral paradigm requires relatively short baseline
      training, examines frequency specification of tinnitus perception, and achieves
      sensitive tinnitus testing at an individual level. To test for tinnitus-related
      anxiety and cognitive impairment, we used the elevated plus maze and Morris water
      maze. Our results showed that not all animals with tinnitus demonstrate anxiety
      and cognitive impairment. Immunocytochemically, we found that animals with
      tinnitus manifested increased Fos-like immunoreactivity (FLI) in both auditory
      and non-auditory structures. The manner in which FLI appeared suggests that lower
      brainstem structures may be involved in acute tinnitus whereas the midbrain and
      cortex are involved in more chronic tinnitus. Meanwhile, animals with tinnitus
      also manifested increased FLI in non-auditory brain structures that are involved
      in autonomic reactions, stress, arousal and attention. Electrophysiologically, we
      found that rats with tinnitus developed increased spontaneous firing in the
      auditory cortex (AC) and amygdala (AMG), as well as intra- and inter-AC and AMG
      neurosynchrony, which demonstrate that tinnitus may be actively produced and
      maintained by the interactions between the AC and AMG.

PMID- 26299843
TI  - Auditory-limbic interactions in chronic tinnitus: Challenges for neuroimaging
      research.
AB  - Tinnitus is a widespread auditory disorder affecting approximately 10-15% of the
      population, often with debilitating consequences. Although tinnitus commonly
      begins with damage to the auditory system due to loud-noise exposure, aging, or
      other etiologies, the exact neurophysiological basis of chronic tinnitus remains
      unknown. Many researchers point to a central auditory origin of tinnitus;
      however, a growing body of evidence also implicates other brain regions,
      including the limbic system. Correspondingly, we and others have proposed models
      of tinnitus in which the limbic and auditory systems both play critical roles and
      interact with one another. Specifically, we argue that damage to the auditory
      system generates an initial tinnitus signal, consistent with previous research.
      In our model, this "transient" tinnitus is suppressed when a limbic
      frontostriatal network, comprised of ventromedial prefrontal cortex and ventral
      striatum, successfully modulates thalamocortical transmission in the auditory
      system. Thus, in chronic tinnitus, limbic-system damage and resulting
      inefficiency of auditory-limbic interactions prevents proper compensation of the
      tinnitus signal. Neuroimaging studies utilizing connectivity methods like resting
      state fMRI and diffusion MRI continue to uncover tinnitus-related anomalies
      throughout auditory, limbic, and other brain systems. However, directly assessing
      interactions between these brain regions and networks has proved to be more
      challenging. Here, we review existing empirical support for models of tinnitus
      stressing a critical role for involvement of "non-auditory" structures in
      tinnitus pathophysiology, and discuss the possible impact of newly refined
      connectivity techniques from neuroimaging on tinnitus research.

PMID- 26299844
TI  - Development of an electrode for the artificial cochlear sensory epithelium.
AB  - An artificial cochlear sensory epithelium has been developed on the basis of a
      new concept that the piezoelectric membrane, which converts mechanical distortion
      into electricity, can mimic the function of the inner hair cell and basilar
      membrane of the mammalian cochlea. Our previous research demonstrated that the
      piezoelectric membrane generated electrical outputs in response to the sound
      stimulation after implantation into the guinea pig cochlea, whereas electrodes
      for the stimulation of spiral ganglion neurons have not been fabricated, and a
      method to fix the device in the cochlea is also required to show proof-of
      concept. In the present study, to achieve proof-of-concept of hearing recovery by
      implantation of the artificial cochlear sensory epithelium, we fabricated new
      electrodes that stick into the cochlear modiolus, which also play a role in the
      fixation of the device in the cochlea. The efficacy of new electrodes for
      fixation of the device in the cochlea and for the stimulation of spiral ganglion
      neurons was estimated in guinea pigs. Four weeks after implantation, we confirmed
      that the devices were in place. Histological analysis of the implanted cochleae
      revealed inconspicuous fibrosis and scar formation compared with the sham
      operated specimens (n = 5 for each). The terminal deoxynucleotidyl transferase
      dUTP nick end labeling method was used to assess cell death due to surgical
      procedures in the cochleae that were harvested after 1 day (n = 6) and 7 days (n
      = 6) of implantation; there was no significant increase in apoptotic cell death
      in the implanted cochleae compared with sham-operated cochleae. In seven animals,
      serial measurements of electrically evoked auditory brainstem responses were
      obtained, with the electrode positioned in the scala tympani and with the
      electrode inserted into the cochlear modiolus. With the insertion of electrodes
      into the cochlear modiolus, significant reduction was achieved in the thresholds
      of electrically evoked auditory brainstem responses compared with those placed in
      the scala tympani (p = 0.028). These findings indicated that the new electrodes
      efficiently fixed the device in the cochlea and were able to stimulate spiral
      ganglion neurons.

PMID- 26299846
TI  - A systematic review of non-surgical treatments for lentigo maligna.
AB  - Lentigo maligna (LM) is the most common melanocytic malignancy of the head and
      neck. If left untreated, LM can progress to lentigo maligna melanoma (LMM).
      Complete surgical excision is the gold standard for treatment, however, due to
      the location, size, and advanced age of patients, surgery is not always
      acceptable. As a result, there is ongoing interest in alternative, less invasive
      treatment modalities. The objective was to provide a structured review of key
      literature reporting the use of radiotherapy, imiquimod and laser therapy for the
      management of LM in patients where surgical resection is prohibited. An
      independent review was conducted following a comprehensive search of the National
      Library of Medicine using MEDLINE and PubMed, Embase, Scopus, ScienceDirect and
      Cochrane Library databases. Data were presented in tabular format, and crude data
      pooled to calculate mean recurrence rates for each therapy. 29 studies met the
      inclusion criteria: radiotherapy 10; topical imiquimod 10; laser therapies 9.
      Radiotherapy demostrated recurrence rates of up to 31% (mean 11.5%), with follow
      up durations of 1-96 months. Topical imiquimod recurrence rates were up to 50%
      (mean 24.5%), with follow-up durations of 2-49 months. Laser therapy yielded
      recurrence rates of up to 100% (mean 34.4%), and follow-up durations of 8-78
      months. in each of the treatment series the I(2) value measuring statistical
      heterogeneity exceeded the accepted threshold of 50% and as such a meta-analysis
      of included data were inappropriate. For non-surgical patients with LM,
      radiotherapy and topical imiquimod were efficacious treatments. Radiotherapy
      produced superior complete response rates and fewer recurrences than imiquimod
      although both are promising non-invasive modalities. There was no consistent body
      of evidence regarding laser therapy although response rates of up to 100% were
      reported in low quality studies. A prospective comparative trial is indicated and
      would provide accurate data on the long-term efficacy and overall utility of
      these treatments.

PMID- 26299845
TI  - Hair cell counts in a rat model of sound damage: Effects of tissue preparation &
      identification of regions of hair cell loss.
AB  - Exposure to intense sound can damage or kill cochlear hair cells (HC). This loss
      of input typically manifests as noise induced hearing loss, but it can also be
      involved in the initiation of other auditory disorders such as tinnitus or
      hyperacusis. In this study we quantify changes in HC number following exposure to
      one of four sound damage paradigms. We exposed adult, anesthetized Long-Evans
      rats to a unilateral 16 kHz pure tone that varied in intensity (114 dB or 118 dB)
      and duration (1, 2, or 4 h) and sacrificed animals 2-4 weeks later. We compared
      two different methods of tissue preparation, plastic embedding/sectioning and
      whole mount dissection, for quantifying hair cell loss as a function of
      frequency. We found that the two methods of tissue preparation produced largely
      comparable cochleograms, with whole mount dissections allowing a more rapid
      evaluation of hair cell number. Both inner and outer hair cell loss was observed
      throughout the length of the cochlea irrespective of sound damage paradigm. Inner
      HC loss was either equal to or greater than outer HC loss. Increasing the
      duration of sound exposures resulted in more severe HC loss, which included all
      HC lesions observed in an analogous shorter duration exposure. 

PMID- 26299847
TI  - Individualized evaluation of cholinesterase inhibitors effects in dementia with
      adaptive cognitive testing.
AB  - Computerized Adaptive Testing (CAT) of cognitive function, selects for every
      individual patient, only items of appropriate difficulty to estimate his or her
      level of cognitive impairment. Therefore, CAT has the potential to combine
      brevity with precision. We retrospectively examined the evaluation of treatment
      effects of cholinesterase inhibitors by CAT using longitudinal data from 643
      patients from a Dutch teaching hospital who were diagnosed with Alzheimer disease
      or Lewy Body disease. The Cambridge Cognitive Examination (CAMCOG) was
      administered before treatment initiation and after intervals of six months of
      treatment. A previously validated CAT was simulated using 47 CAMCOG items.
      Results demonstrated that the CAT required a median number of 17 items (inter
      quartile range 16-20), or a corresponding 64% test reduction, to estimate
      patients' global cognitive impairment levels. At the same time, intraclass
      correlations between global cognitive impairment levels as estimated by CAT or
      based on all 47 CAMCOG items, ranged from 0.93 at baseline to 0.91-0.94 at follow
      up measurements. Slightly more people had substantial decline on the original
      CAMCOG (N = 31/285, 11%) than on the CAT (N = 17/285, 6%). We conclude that CAT
      saves time, does not lose much precision, and therefore deserves a role in the
      evaluation of treatment effects in dementia. Copyright (c) 2015 John Wiley &
      Sons, Ltd.

PMID- 26299848
TI  - Papillary meningioma: an aggressive variant meningioma with clinical features and
      treatment: a retrospective study of 10 cases.
AB  - INTRODUCTION: Papillary meningioma is a rare subtype of malignant meningiomas.
      The aim of this retrospective study was to investigate the clinical,
      radiological, histopathological features and prognosis for papillary meningioma
      at our institutions. MATERIALS AND METHODS: Ten patients with clinically,
      radiologically and histopathologically confirmed papillary meningiomas were
      treated at our hospitals. The clinical data, imaging characteristics,
      histopathological features, surgical treatment and postoperative follow-up, were
      analyzed retrospectively. RESULTS: The patients with a mean age of 36.9 years at
      the time of their initial operations. The papillary meningiomas were
      predominantly located in the convexity (n = 6). At their initial operation, six
      patients underwent gross total resection and four patients underwent subtotal
      resection. The mean post-operative follow-up period was 42.6 months (range: 12-90
      months). Six patients underwent multiple surgical resections. The mean time to
      first recurrence was 21.5 months. On magnetic resonance imaging scan, marked
      enhancements and dural tail signs were displayed in all lesions. All lesions
      showed peritumoral edema. Cysts were seen in four lesions. Bone hyperostosis or
      destruction was seen in six lesions. Cerebrospinal fluid dissemination was seen
      in three lesions. Incomplete surgical resection was associated with recurrence.
      MIB-1 labeling index was associated with progression-free survival for patients
      (p = 0.0442). CONCLUSIONS: Papillary meningioma has a tendency to present in
      middle-aged patients, and it has specific clinical and histopathological
      characteristics. MIB-1 labeling index and the extent of resection might predict
      the recurrence. Cystic formation, peritumoral edema, osseous change and CSF
      dissemination might be neuroimaging characteristics of papillary meningioma,
      especially in recurrence papillary meningioma.

PMID- 26299850
TI  - Leflunomide, a Reversible Monoamine Oxidase Inhibitor.
AB  - A screening study aimed at identifying inhibitors of the enzyme, monoamine
      oxidase (MAO), among clinically used drugs have indicated that the antirheumatic
      drug, leflunomide, is an inhibitor of both MAO isoforms. Leflunomide inhibits
      human MAO-A and MAO-B and exhibits IC<sub>50</sub> values of 19.1 MUM and 13.7
      MUM, respectively. The corresponding K<sub>i</sub> values are 17.7 MUM (MAO-A)
      and 10.1 MUM (MAO-B). Dialyses of mixtures of the MAO enzymes and leflunomide
      show that inhibition of the MAOs by leflunomide is reversible. The principal
      metabolite of leflunomide, teriflunomide (A77 1726), in contrast is not an MAO
      inhibitor. This study concludes that, although leflunomide is only moderately
      potent as an MAO inhibitor, isoxazole derivatives may represent a general class
      of MAO inhibitors and this heterocycle may find application in MAO inhibitor
      design. In this respect, MAO inhibitors are used in the clinic for the treatment
      of depressive illness and Parkinson's disease, and are under investigation as
      therapy for certain types of cancer, Alzheimer's disease and age-related
      impairment of cardiac function. 

PMID- 26299849
TI  - Characterization of highly proliferative secondary tumor clusters along host
      blood vessels in malignant glioma.
AB  - The aim of the present study was to investigate the extensive invasion of tumor
      cells into normal brain tissue, a life-threatening feature of malignant gliomas.
      How invasive tumor cells migrate into normal brain tissue and form a secondary
      tumor structure remains to be elucidated. In the present study, the morphological
      and phenotypic changes of glioma cells during invasion in a C6 glioma model were
      investigated. C6 glioma cells were stereotactically injected into the right
      putamen region of adult Sprague-Dawley rats. The brain tissue sections were then
      subjected to hematoxylin and eosin, immunohistochemical or immunofluorescent
      staining. High magnification views of the tissue sections revealed that C6 cells
      formed tumor spheroids following implantation and marked invasion was observed
      shortly after spheroid formation. In the later stages of invasion, certain tumor
      cells invaded the perivascular space and formed small tumor clusters. These small
      tumor clusters exhibited certain common features, including tumor cell
      multilayers surrounding an arteriole, which occurred up to several millimeters
      away from the primary tumor mass; a high proliferation rate; and similar gene
      expression profiles to the primary tumor. In conclusion, the present study
      revealed that invading tumor cells are capable of forming highly proliferative
      cell clusters along arterioles near the tumor margin, which may be a possible
      cause of the recurrence of malignant glioma. 

PMID- 26299851
TI  - Synthesis and Anticonvulsant Effect of Novel Thiazolidinedione Containing Benzene
      sulfonylurea and Sulfonylthiourea Derivatives.
AB  - A newer series of 1-(4-substitutedphenyl)-3-(4-((2,4-dioxothiazolidin-5
      lidene)methyl)phenyl sulfonyl)urea/thiourea (4a-l) were synthesized for their
      anticonvulsant activity. The activity is attributed to its potential to restrain
      astrocytic Na+, 2HCl, and K+ co-transport similar to torasemide which has
      sulfonylurea in its structure. Torasemide having the similar action as the
      furosemide that obstructs kainic acid-induced electrical discharges observed from
      cortex and it has neuroprotective agents, for instance antagonizing the N-methyl
      D-aspartate (NMDA) and non-NMDA receptors for evaluating antiepileptic activity.
      The structures of new derivatives were established by elemental analysis and
      spectroscopic techniques viz. FTIR, 1H NMR and LC-MS. The all twelve derivatives
      were assessed for anticonvulsant activity at three different doses at 30, 100 and
      300 mg/kg body weight into maximal electroshock (MES) and subcutaneous
      pentylenetetrazole (sports) models. Compounds 4c and 4e were formed to be most
      active among all the derivatives for both the models of anticonvulsant activity.
      Beside these compounds 4g, 4i and 4k also possessed the prominent anticonvulsant
      activity devoid of any neurotoxicity. The sulfonylurea and sulfonylthiourea both
      were proved to be effective anticonvulsant pharmacophore. Other structure
      activity relationships were established by considering the aspect of substitution
      in the lead. 

PMID- 26299852
TI  - [Molecular biology of colorectal cancer in clinical practice].
AB  - The review summarizes current data on the molecular genetic mechanisms underlying
      the pathogenesis of colorectal cancer (CRC) and addresses the connections between
      these mechanisms and biomarkers used for predictive diagnosis, risk
      stratification, prognosis, and predicting response to chemotherapy and tar-geted
      therapy. Evidence of microRNA involvement in the regulation of major signaling
      pathways affected by CRC pathogenesis is discussed, and signaling pathways that
      can be used as targets in the therapy of colorectal cancer are examined. 

PMID- 26299854
TI  - [Glucokinase and glucokinase regulatory proteins as molecular targets for novel
      antidiabetic drugs].
AB  - The impairment of glucose homeostasis leads to hyperglycemia and type-2 diabetes
      mellitus. Glucokinase (GK), an enzyme that catalyzes the conversion of glucose to
      glucose-6-phosphate in pancreatic beta-cells, liver hepatocytes, specific
      hypothalamic neurons, and intestine enterocytes, is a key regulator of glucose
      homeostasis. In hepatocytes, GK controls the glucose uptake and glycogen
      synthesis and inhibits the glucose synthesis via the gluconeogenesis pathway.
      Glucokinase regulatory protein (GKRP) synthesized in hepatocytes acts as an
      endogenous GK inhibitor. During fasting, GKRP binds GK, inactivates it, and
      transports it into the cell nucleus, thus isolating it from the hepatocyte
      carbohydrate metabolism. In the beginning of the 2000s, the research was mainly
      focused on the development and trials of the small molecule GK activators as
      potential antidiabetic glucose-lowering drugs. However, the use of such
      substances increased the risk of hypoglycemia, and clinical studies of most
      synthetic GK activators are currently discontinued. Allosteric inhibitors of the
      GK-GKRP interaction are coming as alternative agents increasing the GK activity
      that can substitute GKA. In this review, we discuss the recent advances and the
      current state of art in the development of potential antidiabetic drugs targeted
      to GK as a key regulator of glucose homeostasis. 

PMID- 26299853
TI  - [Ebola hemorrhagic fever: Properties of the pathogen and development of vaccines
      and chemotherapeutic agents].
AB  - Ebola hemorrhagic fever (EHF) epidemic currently ongoing in West Africa is not
      the first among numerous epidemics in the continent. Yet it seems to be the worst
      EHF epidemic outbreak caused by Ebola virus Zaire since 1976 as regards its
      extremely large scale and rapid spread in the population. Experiments to study
      the agent have continued for more than 20 years. The EHF virus has a relatively
      simple genome with seven genes and additional reading frame resulting from RNA
      editing. While being of a relatively low genetic capacity, the virus can be
      ranked as a standard for pathogenicity with the ability to evade the host immune
      response in uttermost perfection. The EHF virus has similarities with
      retroviruses, but belongs to (-)RNA viruses of a nonretroviral origin. Genetic
      elements of the virus, NIRV, were detected in animal and human genomes. EHF virus
      glycoprotein (GP) is a class I fusion protein and shows more similarities than
      distinctions in tertiary structure with SIV and HIV gp41 proteins and even
      influenza virus hemagglutinin. EHF is an unusual infectious disease, and studying
      the molecular basis of its pathogenesis may contribute to new findings in therapy
      of severe conditions leading to a fatal outcome. 

PMID- 26299855
TI  - [A role of long noncoding RNAs in carcinogenesis].
AB  - The review describes the changes observed in long noncoding RNA (lncRNA) content
      and function at various stages of carcinogenesis, as well as the prospects of
      lncRNA application in cancer prognosis. 

PMID- 26299856
TI  - [Effects of DNA quality on the measurement of telomere length].
AB  - Existing evidence on the association of telomere length with life expectancy and
      the risk of various age related diseases is discordant. This inconsistency in the
      data may be due to methodological factors, e.g., the differences in the
      techniques for measuring telomere length, cell harvesting, DNA isolation, and
      material. One of the general requirements to experiments concerned with the
      measurement of telomere length is the high quality of DNA samples under study.
      The current review considers the most common errors during the measurement of
      telomere length associated with the improper quality of the biological material. 

PMID- 26299858
TI  - [Characterization and cloning of the cry2A gene from indigenous isolates of
      Bacillus thuringiensis].
AB  - Discovery of novel cry genes of Bacillus thuringiensis (Bt) with higher toxicity
      is important for the development of transgenic Bt crops resistant to target
      pests. Two new indigenous isolates of Bt were characterized for their colony
      type, crystal inclusion and toxicity with Helicoverpa armigera Hubner and
      Spodoptera litura Linn. Screening of cry2A genes from the two new isolates of Bt,
      T30 and T48, by PCR with cry2A family primers showed the presence of cry2A genes
      only in the isolate T30. Further screening of these isolates of Bt with three
      different cry2A gene specific primers showed the presence of cry2Aa, cry2Ab and
      cry2Ac genes in both of the new Bt isolates. The cry2A open reading frame (ORF)
      of Bt T48 (~1.9 kb) was amplified and cloned in a T/A vector (~2.8 kb). All the
      E. coli transformants showed only the cry2Aa gene. Comparison of the nucleotide
      sequence data generated from the cry2Aa (~1.9 kb) gene showed a 99 percent
      homology and one amino acid variation when compared with the holotype sequence of
      Cry2Aa1. 

PMID- 26299857
TI  - [Rabies vaccines: Current status and prospects for development].
AB  - Rabies is an infectious disease among humans and animals that remains incurable,
      despite its longstanding research history. The only way to prevent the disease is
      prompt treatment, including vaccination as an obligatory component and
      administration of antirabies immunoglobulin as a supplement. Since the first
      antirabies vaccination performed in the 19th century, a large number of different
      rabies vaccines have been developed. Progress in molecular biology and
      biotechnology enabled the development of effective and safe technologies of
      vaccine production. Currently, new-generation vaccines are being developed based
      on recombinant rabies virus strains or on the production of an individual
      recombinant rabies antigen-glycoprotein (G protein), either as a component of
      nonpathogenic viruses, or in plants, or in the form of DNA vaccines. In this
      review, the main modern trends in the development of rabies vaccines have been
      discussed. 

PMID- 26299859
TI  - [Two Elovl5-like elongase genes in Cyprinus carpio var. Jian: Gene
      characterization, mRNA expression, and nutritional regulation].
AB  - Elovl5 elongase is a critical enzyme involved in the highly unsaturated fatty
      acid (HUFA) biosynthesis. There is very little information on the evolution and
      functional characterization of Elovl5-a and Elovl5-b genes in common carp
      (Cyprinus carpio var. Jian). In the present study, the genomic sequences and
      structures of two putative Elovl5-like elongase genes in the common carp genome
      were obtained. The mRNA expression patterns of Elovl5-a and Elovl5-b in tissues,
      hatching carp embryos, and juveniles under nutritional regulation were
      investigated. The results show that the two Elovl5 elongase genes have similar
      organization, coding 8 exons of high identity and introns of distinct size and
      sequence composition. They are not allelic variants of a single gene. Both Elovl5
      elongase genes are highly expressed in liver, intestine (pyloric caeca) and
      brain. Elovl5-a and Elovl5-b mRNAs showed increased expression from newly hatched
      to 20 days after hatching. The regulation of Elovl5-a and Elovl5-b in response to
      dietary fatty acid composition was determined in liver, brain and intestine
      (pyloric caeca) of common carp fed with diets: (i) fish oil (FO) rich in n-3
      HUFA, (ii) corn oil (CO, 18:2n-6) or (iii) linseed oil (LO, 18:3n-3). Also the
      differential expression of Elovl5-a and Elovl5-b genes in liver, brain and
      intestine in common carps fed with different oil sources was studied. Further
      work aimed at the determination of the mechanisms of differential expression of
      the Elovl5-a and Elovl5-b in different tissues and the roles of transcription
      factors in regulating HUFA synthesis is in progress. 

PMID- 26299860
TI  - [The HHEX rs1111875A/G gene polymorphism is associated with susceptibility to
      type 2 diabetes in the Iranian population].
AB  - The illuminating picture of genetic mechanisms underlying the development of type
      2 diabetes (T2DM) includes differently accumulated genetic polymorphisms that
      increase the risk along with environmental factors. A number of single nucleotide
      polymorphisms (SNPs) are indicated to be linked with T2DM, but also conflicting
      results have been found. To examine the contribution of these polymorphisms in
      conferring susceptibility to T2DM, the association of HHEX rs1111875A/G and
      CDKN2A/B rs10811661C/T common gene polymorphisms with the risk of T2DM in an
      Iranian population was evaluated. In this study participated 140 patients and 140
      controls. Genomic DNA was extracted from samples and genotyping of the
      polymorphisms was performed by the Polymerase Chain Reaction-Restriction Fragment
      Length Polymorphism (PCR-RFLP) technique. A significant association was found
      with the G allele (OR = 1.729, CI = 1.184-2.523, P = 0.004) and GG genotype (OR =
      2.921, 95% CI = 1.789-4.771, P < 0.001) of the rs1111875A/G SNP for
      susceptibility to T2DM in the recessive model. Furthermore, compared with the GG
      genotype, individuals with the GA genotype had a lower risk to develop T2DM (OR =
      0.237, 95% CI = 0.137-0.408, P< 0.001) in the additive model. In addition, an
      association between the polymorphism and BMI in regard to the risk of T2DM was
      identified. The genotype and allele frequencies of the rs10811661C/T polymorphism
      did not show a statistically significant association with T2DM in any genetic
      model. Our results show that the rs1111875A/G polymorphism is an important
      susceptibility polymorphism for the development of T2DM in the Iranian
      population. Also, these findings support that this polymorphism is a key genetic
      risk factor for the development of T2DM in multiple ethnic populations. 

PMID- 26299861
TI  - [The expression profile of Arabidopsis thaliana beta-1,3-glucanase promoter in
      tobacco].
AB  - Well characterized promoters with specific activity only during male gametophyte
      development of transgenic organism are widely utilized in strategies aimed at the
      elimination of unwanted transgene escape from the transgenic to the non
      transgenic plant population. Since the specificity and timing of the applied
      promoter in the original and transgenic organism don't have to be consistent,
      here we have tested by promoter-GUS fusion analysis the APRS promoter isolated
      from Arabidopsis thaliana in transgenic tobacco plants. Unlike of A. thaliana
      transcriptomic microarray data that identified gene expression from this promoter
      in late stages of pollen development, in tobacco plants the APRS promoter was
      active in the developing microspores during a short period of time before the
      microspores are released from the tetrads. Despite these discrepancies, the APRS
      promoter remains strictly pollen specific in tobacco plants. However,
      verification of its specificity in other important crops should precede the use
      of the APRS promoter in the engineered male sterility or in production of
      transgene-free pollen via site-specific recombination systems. 

PMID- 26299862
TI  - [Biochip detection of KRAS, BRAF, and PIK3CA somatic mutations in colorectal
      cancer patients].
AB  - Somatic mutations of KRAS, PIK3CA, and BRAF cause insensitivity of colorectal
      tumors to therapy with anti-EGFR monoclonal antibodies, necessitating a genetic
      testing prior to therapy. A biological microchip was developed and validated to
      allow detection of 19 somatic mutations in KRAS, PIK3CA, and BRAF genes. The
      method combines LNA-clamp PCR and allele-specific hybridization on a microchip
      and detects mutant DNA in 100 times wild-type background (1%). A total of 66 DNA
      samples isolated from colorectal tumors were tested with the biochip. Possible
      associations between the genetic status of the tumor and the patient's
      characteristics (age, sex, tumor localization, stage, and TMN) were assessed
      statistically. KRAS mutations were more common in females (P = 0.02) and in
      patients with distant metastasis (P = 0.04). Other associations between the
      presence of mutations and patient characteristics were not observed. The method
      proved highly sensitive and can be used in oncology to select patients who
      sensitive to therapy with anti-EGFR monoclonal antibodies. 

PMID- 26299863
TI  - [DNA amplification using PCR with abutting primers].
AB  - DNA analysis of nimplex biological objects (wastewater, soil, archaeological and
      forensic samples, etc.) is currently of great interest. DNA of these objects is
      characterized by low suitability for research due to the violation of its
      integrity and chemical structure; thus, the detection of specific nucleic acid
      fragments can be achieved by PCR with contiguous primers. In this paper, we
      present the results that clarify the specific characteristics of PCR with
      abutting primers. The 3'-ends of these primers are annealed at adjacent
      nucleotides of complementary chains of DNA target. It has been shown that the
      proximity of primers enables the formation of specific reaction products with a
      higher sensitivity and less reaction time. Using artificially damaged DNA and DNA
      from the soil we demonstrated that the abutting primers provide assured detection
      of specific DNA fragments. The results of this work may be taken into account in
      PCR with degraded (fragmented) DNA. 

PMID- 26299864
TI  - [Polymorphism of the bphA genes in bacteria destructing biphenyl/chlorinated
      biphenils].
AB  - Polychlorinated biphenyls (PCBs) are persistent organic pollutants. Biphenyl 2,3
      dioxygenase (BDO) is a key enzyme that determines the range of PCBs oxidized by a
      bacterial strain. BDO subunit alpha (BphA1) plays an essential role in substrate
      recognition and binding. The genes for dioxygenases that hydroxylate aromatic
      rings were screened and analyzed phylogenetically. Genes found in biphenyl
      oxidizing Rhodococcus erythropolis strains G12a, B7b, and B106a proved to be
      similar to the published nucleotide sequences of the Rhodococcus sp. HA99 and R04
      and Novosphingobium aromaticivorans F199 bphA1 genes, which code for the alpha
      subunits that do not belong to the biphenyl/toluene dioxygenase (B/TDO) family.
      PCB-destructing R. ruber P25 was found to possess a unique bphA1 gene, which
      clusters together with the phenylpropionate dioxygenase (PPDO) alpha-subunits of
      Mycobacterium vanbaalenii PYR-1 and Frankia sp. EuI1c. The deduced amino acid
      sequences of the genes were analyzed. The amino acids of the BDO active site in
      R. wratislaviensis P1, P12, P13, and P20 (bphA1 genes of the B/TDO family) were
      identical to those of the active PCB degrader R. jostii RHA1. The Rhodococcus
      strains in question were shown to be active toward both orthoand parachlorinated
      ring of 2,4'-dichlorobiphenyl. The alpha-subunit amino acids responsible for the
      substrate specificity of the enzyme in Pseudomonas sp. S9, S13, S210, S211, and
      S212 (B/TDO family) were the same as in P. pseudoalcaligenes KF707. The
      Pseudomonas strains were active toward the para-chlorinated ring of 2,4'
      dichlorobiphenyl. The results of screening bacterial strains for bphA1 can be
      used to identify the biotechnologically promising PCB destructors. 

PMID- 26299865
TI  - [Effects of Ido1 on mouse decidualization].
AB  - Indoleamine 2,3-dioxygenase 1 (Ido1) is a rate-limiting enzyme which converts the
      essential amino acid tryptophan to kynurenine. The aim of this study was to
      investigate the expression and regulation of Ido1 in mouse uterus during
      decidualization. The results showed that Ido1 mRNA expression gradually increased
      from day 1 to 4 of pregnancy and reached the peak level on day 4. On days 5-8 of
      pregnancy, a low level of Ido1 expression was observed in the uteri.
      Simultaneously, Ido1 mRNA was also lowly expressed in the decidualized uterus and
      the stromal cells treated with 8-Br-cAMP. Under in vitro decidualization, the
      expression of Ido1 mRNA gradually declined. Further studies found that
      overexpression of Ido1 can inhibit the expression of decidualization marker genes
      PRL, IGFBP1 and Dtprp under in vitro decidualization while inhibition of Ido1
      with L-1-MT can induce the expression of these marker genes. Ido1 can prevent
      uterine stromal cells proliferation and enhance the expression of the Bax gene
      and increase the Bax/Bcl2 ratio under in vitro decidualization. Additionally,
      Ido1 can also modulate the expression of the MMP2 gene. In the uterine stromal
      cells, estrogen and progesterone can stimulate the expression of Ido1. These data
      indicate that Ido1 may play an important role during mouse decidualization and
      may be regulated by estrogen and progesterone in the uterine stromal cells. 

PMID- 26299866
TI  - [Changes in the number of copies of genetic loci in gastric cancer].
AB  - It is assumed that changes in the number of copies that belong to the basic
      mechanisms that control the expression of genes are important for malignization.
      Therefore, the characterization of these genes and the precise assessment of the
      number of copies are important for understanding the molecular basis of tumor
      emergence and progression in the human organism, as well as for the
      identification of predictive markers of malignization. In the present study, the
      relative number of copies of 19 loci (BAX, GSTP1, CASP3, CASP8, HIF1A, OCT4, C
      MYC, SOX2, BCL2, CASP8/FADD, NANOG, P53, CASP9, IL-10, NFKB1, HV2, and ACTB) in
      cancerous and conventionally healthy tissues from 25 residents of southern Russia
      with a histologically confirmed diagnosis of adenocarcinoma (stages G1-G2 and G3)
      or signet cell gastric cancer were determined by quantitative real-time PCR.
      Changes in the number of copies of the gene were shown to be specific to
      particular histological types of cancer, as well as to depend on the stage of
      tumor cell differentiation. The data suggest that the number of copies of changes
      in the BAX, CASP3, CASP8, OCT4, C-MYC, SOX2, BCL2, NANOG, CASP9, NFKB1, HV2,
      ACTB, MKI67, IL-10, GSTP1, and P53 genes play an important role in the
      malignization of gastric tissue. 

PMID- 26299867
TI  - [DNA methylation in the promoter regions of the laminin family genes in normal
      and breast carcinoma tissues].
AB  - Extracellular glycoproteins of the laminin family are essential components of
      basement membranes involved in a number of biological processes, including tissue
      differentiation, wound healing, and tumorigenesis. We present the first
      comprehensive study of promoter methylation status of the genes encoding laminin
      chains in normal tissues (peripheral blood leucocytes, buccal epithelial cells,
      autopsy breast tissue samples) and in breast carcinoma samples. Based on the
      results of this study, we divide laminin genes into three categories. Genes,
      constitutively methylated in breast tissues include LAMA3A, LAMB2, LAMB3, and
      LAMC2. Genes prone to abnormal methylation in breast carcinoma include LAMA1,
      LAMA2, LAMA3B, LAMA4, LAMB1, and LAMC3. Genes that are rarely if ever methylated
      in breast carcinoma include LAMA5 and LAMC1. The constitutively methylated group
      includes all of the genes that encode subunits of laminin-5 (the historical name
      of laminin 332), the promoters of which were previously considered unmethylated
      in normal tissues and prone to abnormal methylation in breast cancer. 

PMID- 26299868
TI  - [Downregulation of OGDHL expression is associated with promoter hypermethylation
      in colorectal cancer].
AB  - Cell metabolic reprogramming is one of the cancer hallmarks. Glycolysis
      activation, along with suppression of oxidative phosphorylation and, to a lower
      extent, the TCA cycle, occurs in the majority of malignant tumors. A
      bioinformatics search for the glucose metabolism genes that are differentially
      expressed in colorectal cancer (CC) was performed using the data of The Cancer
      Genome Atlas (TCGA) Project. OGDHL for an oxoglutarate dehydrogenase complex
      subunit, which is involved in the TCA cycle and is indirectly responsible for the
      induction of apoptosis, was identified as one of the most promising candidates. A
      quantitative PCR analysis showed, on average, an eightfold downregulation of
      OGDHL in 50% (15/30) of CC samples. Based on the TCGA data, promoter
      hypermethylation was assumed to be a major mechanism of OGDHL inactivation.
      Bisulfite sequencing identified the OGDHL promoter region (+327 ... +767 relative
      to the transcription start site) that is often methylated in CC samples with
      downregulated ODGHL expression (80%, 8/10) and is possibly crucial for gene
      inactivation. Thus, frequent and significant OGDHL downregulation due to
      hypermethylation of a specific promoter region was demonstrated for CC. The OGDHL
      promoter methylation pattern was assumed to provide a marker for differential
      diagnosis of CIMP+ (CpG island methylator phenotype) tumors, which display dense
      hypermethylation of the promoter region in many genes. 

PMID- 26299869
TI  - [Reduced representation bisulfite sequencing design for assessing the methylation
      of human CpG islands in large samples].
AB  - The reduced representation bisulfite sequencing (RRBS) method has been developed
      for the high-throughput analysis of DNA methylation based on the sequencing of
      genomic libraries treated with sodium bisulfite by next-generation approaches. In
      contrast to whole-genome sequencing, the RRBS approach elaborates specific
      endonucleases to prepare libraries in order to produce pools of CpG-rich DNA
      fragments. The original RRBS technology based on the use of the MspI libraries
      allows one to increase the relative number of CpG islands in the pools of genomic
      fragments compared to whole-genome bisulfite sequencing. Nevertheless, this
      technology is rarely used due to the high cost compared with bisulfite
      methylation analysis with hybridization microarrays and significant residual
      amount of data represented by the sequences of genomic repeats that complicates
      the alignment and is not of particular interest for developing DNA methylation
      markers, which is often the main goal of biomedical research. We have developed
      an algorithm for estimating the likelihood that recognition sites of restriction
      endonucleases will be represented in CpG islands and present a method of reducing
      the effective size of the RRBS library without a significant loss of the CpG
      islands based on the use of the XmaI endonuclease for library preparation. In
      silico analysis demonstrates that the optimum range of the XmaI-RRBS fragment
      lengths is 110-200 base pairs. The sequencing of this library allows one to
      assess the methylation status of over 125000 CpG dinucleotides, of which over
      90000 belong to CpG islands. 

PMID- 26299870
TI  - [Identification and polymorphism of the sucrose synthase gene Sus1 in Pisum
      fulvum].

PMID- 26299871
TI  - Molecular tectonics: heterometallic (Ir,Cu) grid-type coordination networks based
      on cyclometallated Ir(III) chiral metallatectons.
AB  - A chiral-at-metal Ir(III) organometallic metallatecton was synthesised as a
      racemic mixture and as enantiopure complexes and combined with Cu(II) to afford a
      heterobimetallic (Ir,Cu) grid-type 2D coordination network.

PMID- 26299872
TI  - 'End of life' conversations, appreciation sequences, and the interaction order in
      cancer clinics.
AB  - OBJECTIVE: To address the organization of conversations in oncology visits by
      taking an "interaction order" perspective and asking how these visits are
      intrinsically organized. METHODS: Conversation analysis. RESULTS: Using audio
      recordings of talk in oncology visits involving patients with non-small cell lung
      cancer, we identify and analyze an "appreciation sequence" that is designed to
      elicit patients' understanding and positive assessment of treatments in terms of
      their prolongation of life. CONCLUSION: An "appreciation sequence," regularly
      initiated after the delivery of scan results and/or treatment recommendations,
      simultaneously reminds patients of their mortality while suggesting that the
      treatment received has prolonged their lives, and in some cases significantly
      beyond the median time of survival. PRACTICE IMPLICATIONS: We explore the
      functions of the appreciation sequence for cancer care and set the stage for
      considering where and when physicians have choices about the order and direction
      the talk can take and how to allocate time for end of life and quality of life
      conversations.

PMID- 26299873
TI  - Low temperature structural anomalies arising from competing exchange interactions
      in pyrochlore Nd2Ru2O7 probed by XRD and EXAFS.
AB  - Quantitative structural parameters of pyrochlore Nd2Ru2O7, with temperature
      dependence, have been derived upon fitting XRD and EXAFS data. An anomalous
      expansion of the lattice parameter and the Ru-O bond length indicates a
      structural instability at low temperatures; in particular, an increase in the non
      thermal term of the mean square fluctuation in the bond length is the evidence
      for a static disorder of Ru atoms. This static disorder is closely correlated
      with a decrease in the average Ru-O-Ru bond angle with decreasing temperature,
      favoring the short-range ferromagnetic coupling in the material. This
      ferromagnetic coupling formed thus triggered the spin frustration at low
      temperature when the contradictory constraints of antiferromagnetic interaction
      act upon the same Ru site in the corner-sharing tetrahedrons of pyrochlore
      Nd2Ru2O7. This study demonstrates that the spin frustration arising from the
      competition of ferromagnetic/antiferromagnetic interactions in pyrochlore
      Nd2Ru2O7 will cause structural instability especially on the atomic scale, which
      provides a new point of view to help understand its particular magnetic state. 

PMID- 26299874
TI  - Extended duration versus standard duration of peginterferon alfa-2a in treatment
      of chronic hepatitis B: A systematic review and meta-analysis.
AB  - In the last decade, PEG-IFNa-2a has been widely used in the treatment of chronic
      hepatitis B (CHB). The current standard duration is 48 weeks; however, several
      studies based on small sample sizes have indicated that treatment extended beyond
      48 weeks improved clinical outcomes than standard 48 weeks of therapy. Therefore,
      we performed a meta-analysis to compare the efficacy and safety of extended
      duration versus standard duration treatment with PEG-IFNa-2a monotherapy for
      patients with CHB. Four studies comprising of 350 patients were included in our
      study. Our analysis showed that extended treatment resulted in a higher HBsAg
      clearance rate compared with the standard treatment at the end of treatment, 24
      and 48 weeks post-treatment [odds ratio (OR)=2.45, 95% confidence intervals (CI)
      (1.17-5.11), P=0.02; OR=3.17, 95% CI (1.62-6.21), P<0.01; OR=5.02, 95% CI (1.63
      15.45), P<0.01, respectively]. Higher HBeAg seroconversion rates were also
      obtained in the extended treatment group than the standard treatment group at the
      end of treatment and 48 weeks post-treatment [OR=2.09, 95% CI (1.10-3.98),
      P=0.02, and OR=2.67, 95% CI (1.39-5.13), P<0.01, respectively]. In addition,
      extended treatment was superior to standard treatment in HBV-DNA inhibition rate
      at 48 weeks post-treatment [OR=3.15, 95% CI (1.51-6.57), P<0.01]. Therefore,
      extended treatment with PEG-IFNa-2a beyond 48 weeks may be a promising strategy
      to achieve higher rates of sustained HBV-DNA inhibition, HBeAg seroconversion and
      HBsAg clearance off-therapy for patients with CHB. 

PMID- 26299875
TI  - Editorial: Essentials in Tooth Development and Regeneration.

PMID- 26299877
TI  - How common are myeloproliferative neoplasms? A systematic review and meta
      analysis.

PMID- 26299876
TI  - Histone Modification in Osteogenic Differentiation of Skeletal Stem Cells.
AB  - Osteogenic differentiation of skeletal stem cells is an integral part of bone
      development and homeostasis, and the perturbation of this process is one of the
      causes to skeletal disease. Understanding of how epigenetic events regulate
      skeletal stem cell differentiation is therefore of great importance. While the
      basic epigenetic modifications leading to bone formation are somewhat under
      explored, a significant amount of research has defined the regulatory roles of
      histone modifications in osteogenic differentiation. The orchestration of histone
      modifications is a requirement to establish the epigenetic status which regulates
      gene transcription during osteogenic differentiation of skeletal stem cells. Here
      we focus on the roles of histone modification during osteogenic differentiation
      and review studies that have advanced our knowledge in the field. Before this
      summary, a brief description is given regarding the up-to-date understanding of
      the definition of skeletal stem cells and the main mechanisms responsible for
      histone modifications. 

PMID- 26299878
TI  - Unicameral bone cyst of the patella in a young dog.
AB  - This report describes a case of a solitary unicameral patellar bone cyst in a
      young dog. A five-month-old, male Dobermann Pinscher dog was referred for a 10
      day left hindlimb lameness. A mild swelling of the peripatellar soft tissues of
      the left patella was detected upon physical examination. Signs of pain were
      elicited upon direct palpation of the patella. Radiographic examination revealed
      an oval radiolucency within the medullary cavity at the base of the left patella.
      Radiographic examination, arthroscopy, and histopathology findings supported the
      diagnosis of a benign patellar bone cyst. The condition was treated by surgical
      curettage and autogenous bone graft harvested from the ipsilateral proximal
      tibia. Clinical signs, including lameness and signs of pain upon deep palpation,
      disappeared three weeks after surgery. Follow-up re-evaluation five years after
      surgery revealed no recurrence of the cyst and the patient was asymptomatic. 

PMID- 26299879
TI  - Evolution of mitochondrial gene order in Annelida.
AB  - Annelida is a highly diverse animal group with over 21,000 described species. As
      part of Lophotrochozoa, the vast majority of annelids are currently classified
      into two groups: Errantia and Sedentaria, together forming Pleistoannelida.
      Besides these taxa, Sipuncula, Amphinomidae, Chaetopteridae, Oweniidae and
      Magelonidae can be found branching at the base of the tree. Comparisons of
      mitochondrial genomes have been used to investigate phylogenetic relationship
      within animal taxa. Complete annelid mitochondrial genomes are available for some
      Sedentaria and Errantia and in most cases exhibit a highly conserved gene order.
      Only two complete genomes have been published from the basal branching lineages
      and these are restricted to Sipuncula. We describe the first complete
      mitochondrial genome sequences for all other basal branching annelid families:
      Owenia fusiformis (Oweniidae), Magelona mirabilis (Magelonidae), Eurythoe
      complanata (Amphinomidae), Chaetopterus variopedatus and Phyllochaetopterus sp.
      (Chaetopteridae). The mitochondrial gene order of all these taxa is substantially
      different from the pattern found in Pleistoannelida. Additionally, we report the
      first mitochondrial genomes in Annelida that encode genes on both strands. Our
      findings demonstrate that the supposedly highly conserved mitochondrial gene
      order suggested for Annelida is restricted to Pleistoannelida, representing the
      ground pattern of this group. All investigated basal branching annelid taxa show
      a completely different arrangement of genes than observed in Pleistoannelida. The
      gene order of protein coding and ribosomal genes in Magelona mirabilis differs
      only in two transposition events from a putative lophotrochozoan ground pattern
      and might be the closest to an ancestral annelid pattern. The mitochondrial
      genomes of Myzostomida show the conserved pattern of Pleistoannelida, thereby
      supporting their inclusion in this taxon.

PMID- 26299880
TI  - Diversification patterns in cosmopolitan earthworms: similar mode but different
      tempo.
AB  - Comparative phylogeography of widespread species that span the same geographic
      areas can elucidate the influence of historical events on current patterns of
      biodiversity, identify patterns of co-vicariance, and therefore aid the
      understanding of general evolutionary processes. Soil-dwelling animals present
      characteristics that make them suitable for testing the effect of the
      palaeogeographical events on their distribution and diversification, such as
      their low vagility and population structure. In this study, we shed light on the
      spatial lineage diversification and cladogenesis of two widely-distributed
      cosmopolitan and invasive earthworms (Aporrectodea rosea and A. trapezoides) in
      their putative ancestral area of origin, the Western Palearctic, and a few
      populations in North America. Molecular analyses were conducted on mitochondrial
      and nuclear markers from 220 (A. rosea) and 198 (A. trapezoides) individuals
      collected in 56 and 57 localities, respectively. We compared the lineage
      diversification pattern, genetic variability and cladogenesis in both species.
      Our findings showed that both species underwent a similar diversification from
      the Western Mediterranean plates to (i) Northern Europe and (ii) the Iberian
      Peninsula, establishing their two main lineages. Their diversification was in
      concordance with the main palaeogeographical events in the Iberian Peninsula and
      Western Mediterranean, followed by a later colonization of North America from
      individuals derived exclusively from the Eurosiberian lineage. Their
      diversification occurred at different times, with the diversification of A. rosea
      being potentially more ancient. Cladogenesis in both species seems to have been
      modelled only by the Mediterranean plate shifts, ignoring historical climatic
      oscillations such as the Messinian salinity crisis. Their high genetic
      variability, strong population structure, lack of gene flow and stepping-stone
      like cladogenesis suggest the existence of different cryptic lineages. Our
      results may indicate a recurrent event in invasive earthworms within their
      ancestral distribution areas in the Western Palearctic. 

PMID- 26299881
TI  - A prospective pilot study in assessing the accuracy of ultrasound estimated fetal
      weight prior to delivery.
AB  - BACKGROUND: Perinatal mortality and morbidity related to growth restriction and
      macrosomia are predicted by birthweight. Estimated fetal weight is a surrogate
      measure for neonatal weight, and accurate measurement of this is central to
      providing counselling and managing preterm birth. AIMS: To assess the accuracy of
      estimated fetal weight (EFW) measured by two sonographers within 1 week of
      delivery using Hadlock formula. MATERIALS AND METHODS: Two sonographers
      independently scanned 150 women with singleton pregnancies, who were booked for
      elective delivery. The sonographers measured four biometric measurements in
      estimating fetal weight. The accuracy of EFW compared to the birthweight was
      examined. We also assessed the sensitivity and specificity for diagnosis of small
      for-gestational age (SGA) and large-for-gestational age (LGA) according to the
      EFW. RESULTS: Estimated fetal weight was similar to actual birthweight, with a
      mean percentage difference (SD) of 1.4(7.0) (P = 0.44). The reliability
      coefficient of EFW compared to actual birthweight was 0.97 (95% CI (0.96, 0.98)).
      There was no significant difference between the sonographers for EFWs and among
      the sonographers from the ultrasound scan to delivery interval. The sensitivity
      and specificity for detection of SGA and LGA were 93.3% and 99.3%, 60% and 95.6%,
      respectively. CONCLUSIONS: There is high reproducibility with minimum discrepancy
      from actual birthweight among sonographers 1 week prior to delivery using Hadlock
      formula with better prediction of SGA neonates.

PMID- 26299882
TI  - Pediatric and adolescent renal cell carcinoma.
AB  - OBJECTIVE: Renal cell carcinoma (RCC) is an uncommon malignancy among children
      and adolescents. Because of this, there has been relatively sparse research and
      evidence on the topic. As the body of research regarding pediatric and adolescent
      RCC has developed in recent years, it has become increasingly clear that it
      demonstrates important differences from the much more common adult-type RCC. This
      review aims to examine and summarize the current literature, with a focus on the
      ways that pediatric and adolescent RCC differ from the adult disease, and to make
      recommendations for evaluation and management based on this evidence whenever
      possible. METHODS AND MATERIALS: A thorough search of all articles relating to
      pediatric and adolescent RCC has been undertaken using PubMed. The reference
      lists from all relevant articles have been further reviewed, to ensure inclusion
      of all pertinent literature. CONCLUSION: The most significant development in
      recent years has been the realization that most of the pediatric and adolescent
      RCC cases, but only a very small fraction of adult RCC cases, demonstrate
      "translocation tumor" pathology. It is likely that such differences may
      eventually explain many of the previous observations regarding differences in
      behavior of RCC among children and teenagers. At this point, however, the
      relevance of translocation pathology to clinical management remains unclear, and
      so most continue to treat these patients in much the same way as those with the
      more conventional tumor subtypes.

PMID- 26299883
TI  - UNC-51-like kinase 1 expression in radical nephrectomy specimens as a predicting
      factor of progression-free survival in patients with metastatic renal cell
      carcinoma treated with mammalian target of rapamycin inhibitors.
AB  - BACKGROUND: To analyze basal expression levels of multiple components in the
      autophagy pathway in radical nephrectomy specimens from patients with metastatic
      renal cell carcinoma (mRCC) treated with mammalian target of rapamycin (mTOR)
      inhibitors, to identify factors predicting susceptibility to these agents.
      METHODS: This study included 48 consecutive patients undergoing radical
      nephrectomy, who were diagnosed with mRCC and subsequently treated with either
      everolimus or temsirolimus. Expression levels of 5 major molecular markers
      involved in the signaling pathway associated with autophagy, including autophagy
      related protein (Atg)5, Atg9, Beclin1, microtubule-associated protein light chain
      3, and UNC-51-like kinase 1 (ULK1), were measured by immunohistochemical staining
      of primary renal cell carcinoma specimens. RESULTS: During the observation period
      of this study (median = 16.2 mo), 36 patients developed disease progression, with
      a median progression-free survival (PFS) period of 7.6 months. Of several factors
      examined, bone metastasis, liver metastasis, and ULK1 expression were shown to
      have significant effects on the response to mTOR inhibitors. PFS was
      significantly correlated with the expression level of ULK1 in addition to bone
      and liver metastases on univariate analysis. Of these significant factors, ULK1
      expression and liver metastasis were independently associated with PFS on
      multivariate analysis. CONCLUSIONS: It may be useful to consider expression
      levels of potential molecular markers in the autophagy pathway, particularly
      ULK1, in addition to conventional parameters, when selecting patients with mRCC
      who are likely to benefit from treatment with mTOR inhibitors.

PMID- 26299884
TI  - Hepatitis B virus intergenotypic recombinants worldwide: An overview.
AB  - Novel variants generated by recombination events between different hepatitis B
      virus (HBV) genotypes have been increasingly documented worldwide, and the role
      of recombination in the evolutionary history of HBV is of significant research
      interest. In the present study, large-scale data retrieval and analysis on HBV
      intergenotypic recombinant genomes were performed. The geographical distribution
      of HBV recombinants as well as the molecular processes involved in recombination
      were examined. After review of published data, a total of 436 complete HBV
      sequences, previously identified as recombinants, were included in the
      recombination detection analysis. About 60% of HBV recombinants were B/C (n=179)
      and C/D (n=83) hybrids. A/B/C, A/C, A/C/G, A/D, A/E, A/G, B/C/U (U=unknown
      genotype), C/F, C/G, C/J, D/E, D/F, and F/G hybrids were additionally identified.
      HBV intergenotypic sequences were reported in almost all geographical regions
      with similar circulation patterns as their original genotypes, indicating the
      potential for spreading in a wide range of human populations and developing their
      own epidemiology. Recombination breakpoints were non-randomly distributed in the
      genome, and specific favored sites detected, such as within nt 1700-2000 and 2100
      2300 regions, which displayed a statistically significant difference in
      comparison with the remaining genome. Elucidation of the effects of recombination
      events on the evolutionary history of HBV is critical to understand current and
      future evolution trends. 

PMID- 26299885
TI  - Dual regulatory effects of non-coding GC-rich elements on the expression of
      virulence genes in malaria parasites.
AB  - As the primary virulence factor of falciparum malaria, var genes harboring
      mutually exclusive expression pattern lead to antigenic variation and immune
      evasion of this pathogen in human host. Although various mechanisms contribute to
      silence of var genes, little is known of transcriptional activation pathways of a
      single var gene and maintenance of its active state with other silent var loci.
      Here, we report a monoallelic expression pattern of the non-coding GC-elements
      flanking chromosomal internal var genes, and transcript from the active one was
      required for activation of the var gene in the same array. Meanwhile, GFP
      reporter assays revealed a repressive effect on the adjacent gene induced by DNA
      motifs of the insulator-like GC-element, which was linked to heterochromatin
      subnuclear localization. Taken together, these data for the first time provide
      experimental evidence of the dual cis- and trans-acting regulatory functions of
      the GC-elements in both silence and activation of var genes, which would advance
      our understanding of the complex regulatory network of the virulence gene family
      in P. falciparum. 

PMID- 26299886
TI  - Genetic and resistance phenotypic subtyping of Salmonella Saintpaul isolates from
      various food sources and humans: Phylogenetic concordance in combinatory
      analyses.
AB  - Bacterial pathogen subtyping for public health traceback of foodborne outbreaks
      has increasingly produced a number of disparate molecular techniques of varying
      resolution. Here, we bridge the molecular divide across three methodologies,
      transform data types for cross-comparison, and test phylogenetic concordance.
      Single nucleotide polymorphism (SNP) discovery was combined with pulsed-field gel
      electrophoresis (PFGE) and antimicrobial susceptibility profiles for identifying
      and differentiating 183 strains of closely related Salmonella enterica serovar
      Saintpaul isolates from retail meats, produce-associated outbreaks, and clinical
      sources. Fifty-six SNPs across 30 different genes were identified by comparative
      genomic analysis. These SNPs stratified general, monophyletic S. Saintpaul
      serovar specific signatures down to informative strain-specific markers. This SNP
      panel resulted in 17 distinct genotypes that, in concert with standard PFGE
      profiling, generated additional discriminatory power among clonal swarms of
      isolates when the data were transformed into a cross-comparable binary format. In
      a limited number of cases, antimicrobial susceptibility profiles (ASP) provided
      additional attributes for some strains when combined similarly. However, as
      expected from presumably acquired elements, resistant and susceptible populations
      produced some conflicting signals in most clonal complexes but they remained
      largely undisruptive to the general concordance. Taken in concert together, the
      three datasets (SNPs, PFGE,ASP) yielded a matrix of 156 independent phylogenetic
      characters that were statistically evaluated and found to be largely congruent,
      resulting in a consistently structured, non-homoplastic, phylogenetic signal and
      tree topology. 

PMID- 26299888
TI  - Sacral nerve stimulation for faecal incontinence and constipation in adults.
AB  - BACKGROUND: Faecal incontinence (FI) and constipation are both socially
      embarrassing and physically-disabling conditions that impair quality of life. For
      both, surgery may be required in a minority of people when more conservative
      measures fail. However, the invasiveness and irreversible nature of direct
      surgery on bowel and sphincter muscles, poor long-term outcomes and well
      established compIications makes such procedures unappealing for these benign
      conditions. A less-invasive surgical option to treat faecal incontinence and
      constipation is direct, low-voltage stimulation of the sacral nerve roots, termed
      sacral nerve stimulation (SNS). SNS has become the first line surgical treatment
      for FI in people failing conservative therapies. Its value in the treatment of
      constipation is less clear. OBJECTIVES: To assess the effects of sacral nerve
      stimulation using implanted electrodes for the treatment of faecal incontinence
      and constipation in adults. SEARCH METHODS: We searched the Cochrane Incontinence
      Group Specialised Register, which contains trials identified from the Cochrane
      Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process,
      ClinicalTrials.gov, the World Health Organization (WHO) ICTRP and handsearched
      journals and conference proceedings (searched 5 February 2015), EMBASE (1 January
      1947 to 2015 Week 5), and the reference lists of retrieved relevant articles.
      SELECTION CRITERIA: All randomised or quasi-randomised trials assessing the
      effects of SNS for faecal incontinence or constipation in adults. DATA COLLECTION
      AND ANALYSIS: Two review authors independently screened the search results,
      assessed the methodological quality of the included trials, and undertook data
      extraction. MAIN RESULTS: Six crossover trials and two parallel group trials were
      included.Six trials assessed the effects of SNS for FI. In the parallel group
      trial conducted by Tjandra, 53 participants with severe FI in the SNS group
      experienced fewer episodes of faecal incontinence compared to the control group
      who received optimal medical therapy (mean difference (MD) -5.20, 95% confidence
      interval (CI) -9.15 to -1.25 at 3 months; MD -6.30, 95% CI -10.34 to -2.26 at 12
      months). Adverse events were reported in a proportion of participants: pain at
      implant site (6%), seroma (2%) and excessive tingling in the vaginal region
      (9%).In the parallel group trial carried out by Thin, 15 participants with FI in
      the SNS group experienced fewer episodes of FI compared with the percutaneous
      tibial nerve stimulation (PTNS) group (MD -3.00, 95% CI -6.61 to 0.61 at 3
      months; MD -3.20, 95% CI -7.14 to 0.74 at 12 months). Adverse events were
      reported in three participants: mild ipsilateral leg pain during temporary
      testing (n = 1); and stimulator-site pain following insertion of neurostimulator
      (n = 2).In the crossover trial by Leroi 7 of 34 recruited participants were
      excluded from the crossover due mainly to complications or immediate device
      failure. Twenty-four of the remaining 27 participants while still blinded chose
      the period of stimulation they had preferred. Outcomes were reported separately
      for 19 participants who preferred the 'on' and five who preferred the 'off'
      period. For the group of 19, the median (range) episodes of faecal incontinence
      per week fell from 1.7 (0 to 9) during the 'off' period to 0.7 (0 to 5) during
      the 'on' period; for the group of five, however, the median (range) rose from 1.7
      (0 to 11) during the 'off' period compared with 3.7 (0 to 11) during the 'on'
      period. Four of 27 participants experienced an adverse event resulting in removal
      of the stimulator.In the crossover trial by Sorensen and colleagues, participants
      did not experience any FI episodes in either the one-week 'on' or 'off'
      periods.In the crossover trial by Vaizey, participants reported an average of
      six, and one, episodes of faecal incontinence per week during the 'off' and 'on'
      periods respectively in two participants with FI. Neither study reported adverse
      events.In the crossover trial by Kahlke, 14 participants with FI experienced
      significantly lower episodes of FI per week during the stimulator 'on' (1 (SD,
      1.7)) compared with the 'off' period (8.4 (SD, 8.7)). Adverse events reported
      include: haematoma formation (n = 3); misplacement of tined lead (1); and pain at
      stimulator site (n = 1).Two trials assessed SNS for constipation. In the Kenefick
      trial, the two participants experienced an average of two bowel movements per
      week during the 'off' crossover period, compared with five during the 'on'
      period. Abdominal pain and bloating occurred 79% of the time during the 'off'
      period compared with 33% during the 'on' period. No adverse events occurred. In
      contrast, in the trial by Dinning with 59 participants, SNS did not improve
      frequency of bowel movements and 73 adverse events were reported, which included
      pain at site of the implanted pulse generator (32), wound infection (12), and
      urological (17) events. AUTHORS' CONCLUSIONS: The limited evidence from the
      included trials suggests that SNS can improve continence in a proportion of
      patients with faecal incontinence. However, SNS did not improve symptoms in
      patients with constipation. In addition, adverse events occurred in some patients
      where these were reported. Rigorous high quality randomised trials are needed to
      allow the effects of SNS for these conditions to be assessed with more certainty.

PMID- 26299889
TI  - A novel method for measuring TBAb activity in TSAb- and TBAb-positive serum.
AB  - We reported a conversion assay in which thyroid blocking antibody (TBAb) function
      as thyroid stimulating antibody (TSAb). TBAb-bound porcine thyroid cells (PTC)
      were made by incubating TBAb(+) serum and PTC for 1 hour. When these TBAb-bound
      PTC were incubated 4 h with rabbit anti-human (h) IgG antibody (Ab), cAMP
      production was high, but when incubated with normal rabbit serum (NRS) cAMP
      production was low. TBAb-Mnoclonal Ab (MoAb) (KI-70) showed similar conversion.
      However, when TSAb-MoAb(M22) was assayed, anti-hIgG Ab-produced cAMP was lower
      than NRS-produced cAMP. When a mixture of M22 and KI-70 was assayed, anti-hIgG Ab
      produced cAMP was higher than NRS. Thus, it is possible to determine existence of
      TBAb in TSAb(+)serum when anti-IgG Ab-produced cAMP is higher than NRS-produced
      cAMP. In this assay TBAb activity in TSAb(+)serum was scored as positive, gray
      zone and negative when the difference [anti-hIgG Ab-produced cAMP(%)-NRS-produced
      cAMP(%)] was >100%, 50-100% and <+/-50%, respectively. In TSAb(+)sera of Graves'
      patients with no treatment or anti-thyroid therapy, positive TBAb was 9% (3/33
      )and 6.9% (5/72), and gray zone was 18 % (6/33) and 25% (18/72), respectively. A
      low prevelance of TBAb and low TBAb activity (<200% as cAMP) was found in these
      Graves' patients. A radioisotope treated Graves' patient showed existence of both
      TSAb and TBAb at 5 months (NRS, 800% cAMP and anti-IgGAb,1,350% cAMP), and highly
      positive TBAb (NRS, 180% cAMP and anti-hIgG Ab, 3,200% cAMP) at 30 months. This
      conversion assay is useful principally for TBAb determination but is also useful
      for TBAb determination in TSAb(+)serum. 

PMID- 26299890
TI  - The doubt-certainty continuum in psychopathology, lay thinking, and science.
AB  - This paper presents a theoretical model suggesting that doubt and certainty are
      two extremes of a continuum. Different people can be located in different
      locations on this continuum, according to how much they tend to seek refutation
      vs. confirmation. In both ends of the continuum lay mental disorders, which can
      be seen as extreme deviations from the usual relatively stable equilibrium
      between the two thinking processes. One end is defined by excessive skepticism
      and manifested as obsessive compulsive disorder (OCD), a disorder characterized
      by incessant doubt. The other end is defined by excessive certainty and lack of
      doubt, manifested as delusional disorders. Throughout this article, we
      demonstrate that the differences between normative thoughts and delusional
      thoughts are relatively vague, and that in general, the human default tendency is
      to prefer certainty over doubt. This preference is reflected in the confirmation
      bias as well as in other cognitive constructs such as overconfidence and
      stereotypes. Recent perspectives on these biases suggest that the human
      preference for confirmation can be explained in evolutionary terms as adaptive
      and rational. A parallel view of the scientific enterprise suggests that it also
      requires a certain equilibrium between skepticism and confirmation. We conclude
      by discussing the importance of the dialectic relationship between confirmation
      and refutation in both lay thinking and scientific thought.

PMID- 26299891
TI  - An effective attentional set for a specific colour does not prevent capture by
      infrequently presented motion distractors.
AB  - An organism's survival depends on the ability to rapidly orient attention to
      unanticipated events in the world. Yet, the conditions needed to elicit such
      involuntary capture remain in doubt. Especially puzzling are spatial cueing
      experiments, which have consistently shown that involuntary shifts of attention
      to highly salient distractors are not determined by stimulus properties, but
      instead are contingent on attentional control settings induced by task demands.
      Do we always need to be set for an event to be captured by it, or is there a
      class of events that draw attention involuntarily even when unconnected to task
      goals? Recent results suggest that a task-irrelevant event will capture attention
      on first presentation, suggesting that salient stimuli that violate contextual
      expectations might automatically capture attention. Here, we investigated the
      role of contextual expectation by examining whether an irrelevant motion cue that
      was presented only rarely (~3-6% of trials) would capture attention when
      observers had an active set for a specific target colour. The motion cue had no
      effect when presented frequently, but when rare produced a pattern of
      interference consistent with attentional capture. The critical dependence on the
      frequency with which the irrelevant motion singleton was presented is consistent
      with early theories of involuntary orienting to novel stimuli. We suggest that
      attention will be captured by salient stimuli that violate expectations, whereas
      top-down goals appear to modulate capture by stimuli that broadly conform to
      contextual expectations. 

PMID- 26299892
TI  - Prevalence and characteristics of misreporting of energy intake in US adults:
      NHANES 2003-2012.
AB  - Using data from the National Health and Nutrition Examination Survey (NHANES)
      2003-2012, we investigated the prevalence and characteristics of under-reporting
      and over-reporting of energy intake (EI) among 19 693 US adults >=20 years of
      age. For the assessment of EI, two 24-h dietary recalls were conducted using the
      US Department of Agriculture Automated Multiple-Pass Method. Under-reporters,
      acceptable reporters and over-reporters of EI were identified by two methods
      based on the 95 % confidence limits: (1) for agreement between the ratio of EI to
      BMR and a physical activity level for sedentary lifestyle (1.55) and (2) of the
      expected ratio of EI to estimated energy requirement (EER) of 1.0. BMR was
      calculated using Schofield's equations. EER was calculated using equations from
      the US Dietary Reference Intakes, assuming 'low active' level of physical
      activity. The risk of being an under-reporter or over-reporter compared with an
      acceptable reporter was analysed using multiple logistic regression. Percentages
      of under-reporters, acceptable reporters and over-reporters were 25.1, 73.5 and
      1.4 %, respectively, based on EI:BMR, and 25.7, 71.8 and 2.5 %, respectively,
      based on EI:EER. Under-reporting was associated with female sex, older age, non
      Hispanic blacks (compared with non-Hispanic whites), lower education, lower
      family poverty income ratio and overweight and obesity. Over-reporting was
      associated with male sex, younger age, lower family poverty income ratio, current
      smoking (compared with never smoking) and underweight. Similar findings were
      obtained when analysing only the first 24-h recall data from NHANES 1999-2012 (n
      28 794). In conclusion, we found that misreporting of EI, particularly under
      reporting, remains prevalent and differential in US adults. 

PMID- 26299893
TI  - Soft drink consumption is positively associated with metabolic syndrome risk
      factors only in Korean women: Data from the 2007-2011 Korea National Health and
      Nutrition Examination Survey.
AB  - OBJECTIVE: To examine the association between sugar-sweetened beverage
      consumption and metabolic syndrome risk factors in Korean adults. METHODS: We
      used data from 13,972 participants (5432 men and 8540 women) aged >=30 years,
      from the 2007-2011 Korea National Health and Nutrition Examination Survey. The
      subjects were divided into six groups based on their soft drink consumption
      levels from a food frequency questionnaire. Dietary sugar intake was compared
      among groups using 24-hour dietary recall data. RESULTS: The highest soft drink
      consumption frequency category was >=4 times per week, observed in 4.6% of men
      and 1.7% of women. The percentage of energy from total sugar and sugar in
      processed foods increased with increased soft drink consumption in both men and
      women. In the highest consumption group, the percentage of energy from sugar in
      processed foods was 8.9% in men and 11.0% in women. After adjusting for potential
      confounding variables, greater consumption of soft drinks was positively
      associated with all of the components of metabolic syndrome, except the high
      density lipoprotein (HDL) cholesterol level, in women only. Women who consumed
      soft drinks >=4 times per week had a 74% higher risk of metabolic syndrome
      compared to those who consumed soft drinks infrequently (OR: 1.74; 95% CI: 1.00
      3.03; P for trend <0.0001). CONCLUSION: High levels of soft drink consumption
      might constitute an important determinant of metabolic syndrome and its
      components only in Korean adult women.

PMID- 26299894
TI  - Doxycycline assay hair samples for testing long-term compliance treatment.
AB  - OBJECTIVES: Many patients undergoing long-term doxycycline treatment do not
      regularly take their treatment because of photosensitivity. Our objective was to
      create an assay for determining doxycycline levels and to use hair samples for
      monitoring the compliance over a longer period of time. METHODS: We tested sera
      and hair samples from patients treated with doxycycline by a suitable ultra-high
      performance liquid chromatography (UHPLC) based assay. RESULTS: We estimated that
      the speed of hair growth is roughly 1.25 cm per month and we were able to
      determine doxycycline levels over a 6-month period. We tested 14 patients treated
      with doxycycline and we found similar levels of doxycycline in the serum and the
      hair samples representing the last 4 months. Linear regression analysis revealed
      that the level of doxycycline in the serum remained stable over time (p = 0.7)
      but the level of doxycycline in the hair decreased significantly over time (p =
      0.03) indicating a degradation of this molecule in the hair. We detected two
      patients who did not have antibiotic in the hair, indicating a lack of compliance
      that was also confirmed by interview. CONCLUSION: Hair samples can be used to
      test long-term compliance in patients to explain failures or relapses.

PMID- 26299895
TI  - Application of Umbilical Artery Classification in Complicated Monochorionic
      Twins.
AB  - We report our experience on the application of Gratacos' classification in a
      cohort of monochorionic pregnancies complicated by selective intra-uterine growth
      retardation based on the Doppler assessment of the umbilical artery. MATERIALS
      AND METHODS: A retrospective study was conducted on 52 cases of monochorionic
      twin pregnancies, in which one twin presented an abdominal circumference at or
      below the 10th percentile for gestational age. Cases were classified into three
      types according to the umbilical artery Doppler in the smaller twin.
      Subsequently, patients were divided into two groups: the selective IntraUterine
      Growth Retardation group and the Twin-to-Twin Transfusion Syndrome (TTTS) group.
      RESULTS: Of the total 52 cases, 37 were classified as Type I, 12 as Type II, and
      3 as Type III cases. In the total group, progressive fetal deterioration of the
      smaller fetus requiring active management was observed in 66.7% of Type II and
      11.1% of Type I cases (p < .001), and in no Type III case. Unexpected fetal death
      of the smaller twin was observed more frequently in Type III (two cases, 66.7%)
      than in Types I and II cases (5% and 33%, respectively). Among the 52 cases, TTTS
      with oligo-polyhydramnios sequence was diagnosed in 10 cases. The remaining 42
      cases were therefore defined as selective intra-uterine growth retardation. In
      the selective IntraUterine Growth Retardation group, results were similar to
      those obtained for the whole population. CONCLUSIONS: Classification of
      complicated monochorionic twins based on the umbilical artery Doppler is
      particularly important for counseling, even when we include TTTS cases, and
      permits the prediction of clinical evolution and perinatal outcome.

PMID- 26299896
TI  - Optimization of Caco-2 and HT29 co-culture in vitro cell models for permeability
      studies.
AB  - The purpose of this study was to investigate the appropriate proportion of Caco-2
      and HT29 co-culture in vitro cell models for permeability studies. The results
      showed that the transepithelial electrical resistance values of 9:1 and 1:0
      groups (263 +/- 3.61 and 300 +/- 7.55) after 21-day culture were >250 Omega
      cm(2), which were suitable for further experiments. The confocal laser microscopy
      showed that the group of 9:1 (Caco-2:HT29) had the highest integrity, whereas the
      group of 0:1 (Caco-2:HT29) exhibited the lowest. The staining study confirmed
      that mucus was successfully produced by HT29 cells, and it was also produced in
      co-cultures with Caco-2 cells model, but the Caco-2 monocultures did not have any
      blue staining, which made us affirm that mucus is only produced in the presence
      of HT29 cells. The real-time PCR results showed that the total highest expression
      level of ALPi and MUC5AC was the ratio of 9:1 (Caco-2:HT29) and lowest is 1:1
      (Caco-2:HT29). So we concluded that 9:1 (Caco-2:HT29) is the optimal Caco-2 to
      HT29 ratio in the in vitro model co-culture for permeability studies. 

PMID- 26299897
TI  - Folic acid-targeted magnetic Tb-doped CeF3 fluorescent nanoparticles as bimodal
      probes for cellular fluorescence and magnetic resonance imaging.
AB  - Magnetic fluorescent nanoparticles (NPs) have great potential applications for
      diagnostics, imaging and therapy. We developed a facile polyol method to
      synthesize multifunctional Fe3O4@CeF3:Tb@CeF3 NPs with small size (<20 nm), high
      water solubility and good biocompatibility. The NPs were modified by ligand
      exchange reactions with citric acid (CA) to obtain carboxyl-functionalized NPs
      (Fe3O4@CeF3:Tb@CeF3-COOH). Folic acid (FA) as an affinity ligand was then
      covalently conjugated onto NPs to yield Fe3O4@CeF3:Tb@CeF3-FA NPs. They were then
      applied as multimodal imaging agents for simultaneous in vitro targeted
      fluorescence imaging and magnetic resonance imaging (MRI) of HeLa cells with
      overexpressed folate receptors (FR). The results indicated that these NPs had
      strong luminescence and enhanced T2-weighted MR contrast and would be promising
      candidates as multimodal probes for both fluorescence and MRI imaging. 

PMID- 26299898
TI  - A simple method for selecting spawning-ready individuals out from laboratorial
      cultured amphioxus population.
AB  - Amphioxus is an emerging model organism for evolutionary developmental (Evo-Dev)
      studies owing to its key phylogenetic position in chordates. However, the rare
      supply of living embryonic materials is a major drawback for using amphioxus as a
      laboratorial model animal. Although the problem has been partially resolved in
      several recent reports, the spawning of amphioxus still remains unpredictable to
      some extent. In the present study, we reported an accurate method to distinguish
      spawning-ready and non-spawning-ready individuals of amphioxus Branchiostoma
      belcheri. In comparison with non-spawning-ready amphioxus, all spawning-ready
      individuals display following features several hours before their spawning: 1)
      for both males and females, the interstices between two adjacent gonads are
      obvious and relatively wide; and 2) the connections among eggs are loose and the
      crannies appear in each individual ovary of females. These morphological features
      were also observed in B. japonicum, indicating their conservation among different
      lancelet species. Based on this observable criterion, we made predictions on the
      spawning of about 600 ripe B. belcheri individuals and acquired an accuracy of
      86.7% for females and 80.4% for males. In addition, we found that advancing or
      delaying onset of darkness has no detectable effect on the timing of spawning of
      B. belcheri. Our study makes amphioxus spawning more amenable for our experiments
      and will greatly facilitate its utilization as a laboratorial model animal.

PMID- 26299899
TI  - Negative pressure and nanocrystalline silver dressings for nonhealing ulcer: A
      randomized pilot study.
AB  - Chronic wounds have a high prevalence and wound care, treatment, and prevention
      consume large quantities of resources. Chronic wounds are a growing challenge for
      clinicians. A prospective randomized pilot study was conducted to assess the
      effectiveness in terms of reduction in area and safety of the combined use of
      negative-pressure wound therapy and nanocrystalline silver dressings as compared
      to negative pressure wound therapy (NPWT) alone in the management of outpatients
      with chronic wounds. A total of 17 patients were included in the study, 10 were
      treated with the combined method and 7 with NPWT. Patients were followed for 6
      weeks, with a final assessment at 3 months. Clinical improvement, microbiologic
      data, and toxicity of silver were evaluated. The antibacterial effects of ionic
      silver together with the development of granulation tissue promoted by NPWT
      reduced significantly the median extension of the wound between weeks 3 and 6 of
      treatment. The combination with silver also reduced bacterial colonization with
      Pseudomonas aeruginosa and the bacterial load on the surface of the wound. The
      silver levels correlated positively with the extension of the wound, although in
      none of the patients' toxic levels were reached. The combination of NPWT with
      nanocrystalline silver dressings was safe and as effective as NPWT alone. 

PMID- 26299900
TI  - Active Constituents from Drynaria fortunei Rhizomes on the Attenuation of
      Abeta(25-35)-Induced Axonal Atrophy.
AB  - Axonal regeneration might contribute to the restoration of damaged neuronal
      networks and improvement of memory deficits in a murine Alzheimer's disease (AD)
      model. A search for axonal regenerative drugs was performed to discover novel
      therapeutic options for AD. In this study, an aqueous extract of Drynaria
      fortunei rhizomes reversed Abeta25-35-induced axonal atrophy in cultured cortical
      neurons of mice. Bioassay-guided fractionation of this extract led to the
      isolation and identification of compounds 1-5. Among them, (2S)-neoeriocitrin (2)
      and caffeic acid 4-O-glucoside (4) showed significant axonal elongation effects
      on Abeta25-35-induced atrophy. 

PMID- 26299901
TI  - The facile synthesis of hollow Au nanoflowers for synergistic chemo-photothermal
      cancer therapy.
AB  - A novel, mild and facile synthetic route was first developed to fabricate hollow
      Au nanoflowers (designated as H-AuNFs) with drug loading capacity, superior
      photothermal conversion property and pH/NIR dual-responsive drug delivery
      performance. 

PMID- 26299902
TI  - Genetic and antigenic characterization of H5N1 viruses of clade 2.3.2.1 isolated
      in India.
AB  - The recurrent circulation of highly pathogenic avian influenza (HPAI) H5N1 in
      Indian poultry since 2006 resulted in emergence of the viruses of distinct
      antigenic clades of haemagglutinin (HA) with the majority of the H5N1 outbreaks
      since 2011 belonging to clade 2.3.2.1. The present study was aimed to
      characterize the antigenic profile of a collection of H5N1 HPAI viruses of clade
      2.3.2.1 isolated in India by applying antigenic cartography, serological data and
      phylogenetic analysis. Eleven H5N1 viruses (2 of clade 2.2 and 9 of clade
      2.3.2.1) were selected based on genetic analysis and were further characterized
      by antigenic cartography analysis based on cross HI (hemagglutination inhibition)
      data. This study highlights the intercladal antigenic differences between clades
      2.3.2.1 and 2.2 and the intracladal antigenic divergence among the clade 2.3.2.1
      viruses. Five viruses of clade 2.3.2.1 were also studied for analysis of
      glycosylation pattern of Hemagglutinin (HA) gene and the growth kinetics analysis
      in MDCK cells in which the viruses CL03485/H5N1 and 03CL488/H5N1 showed better
      replication kinetics than other viruses. The study presents a baseline data of
      antigenicity and other factors that can be used in the selection of suitable H5
      vaccine strains or HA donor viruses to develop H5 vaccine strains by reverse
      genetics or other methods for control of currently circulating H5N1 viruses in
      Indian region. 

PMID- 26299903
TI  - Parathyroid imaging and successful Parathyroidectomy.

PMID- 26299904
TI  - Transient optogenetic inactivation of the medial entorhinal cortex biases the
      active population of hippocampal neurons.
AB  - The mechanisms that enable the hippocampal network to express the appropriate
      spatial representation for a particular circumstance are not well understood.
      Previous studies suggest that the medial entorhinal cortex (MEC) may have a role
      in reproducibly selecting the hippocampal representation of an environment. To
      examine how ongoing MEC activity is continually integrated by the hippocampus, we
      performed transient unilateral optogenetic inactivations of the MEC while
      simultaneously recording place cell activity in CA1. Inactivation of the MEC
      caused a partial remapping in the CA1 population without diminishing the degree
      of spatial tuning across the active cell assembly. These changes remained stable
      irrespective of intermittent disruption of MEC input, indicating that while MEC
      input is integrated over long time scales to bias the active population, there
      are mechanisms for stabilizing the population of active neurons independent of
      the MEC. We find that MEC inputs to the hippocampus shape its ongoing activity by
      biasing the participation of the neurons in the active network, thereby
      influencing how the hippocampus selectively represents information.

PMID- 26299905
TI  - Ab initio structure determination of n-diamond.
AB  - A systematic computational study on the crystal structure of n-diamond has been
      performed using first-principle methods. A novel carbon allotrope with hexagonal
      symmetry R32 space group has been predicted. We name it as HR-carbon. HR-carbon
      composed of lonsdaleite layers and unique C3 isosceles triangle rings, is stable
      over graphite phase above 14.2 GPa. The simulated x-ray diffraction pattern,
      Raman, and energy-loss near-edge spectrum can match the experimental results very
      well, indicating that HR-carbon is a likely candidate structure for n-diamond. HR
      carbon has an incompressible atomic arrangement because of unique C3 isosceles
      triangle rings. The hardness and bulk modulus of HR-carbon are calculated to be
      80 GPa and 427 GPa, respectively, which are comparable to those of diamond. C3
      isosceles triangle rings are very important for the stability and hardness of HR
      carbon. 

PMID- 26299906
TI  - Human multidrug-resistant Mycobacterium bovis infection in Mexico.
AB  - Here, we describe the molecular characterization of six human Mycobacterium bovis
      clinical isolates, including three multidrug resistant (MDR) strains, collected
      in Mexico through the National Survey on Tuberculosis Drug Resistance (ENTB
      2008), a nationally representative survey conducted during 2008-2009 in nine
      states with a stratified cluster sampling design. The genetic background of
      bovine M. bovis strains identified in three different states of Mexico was
      studied in parallel to assess molecular relatedness of bovine and human strains.
      Additionally, resistance to first and second line anti-tuberculosis (TB) drugs
      and molecular identification of mutations conferring drug resistance was also
      performed. All strains were characterized by spoligotyping and 24-loci MIRU
      VNTRs, and analyzed using the SITVIT2 (n = 112,000 strains) and SITVITBovis (n =
      25,000 strains) proprietary databases of Institut Pasteur de la Guadeloupe.
      Furthermore, data from this study (n = 55 isolates), were also compared with
      genotypes recorded for M. bovis from USA (n = 203), Argentina (n = 726), as well
      as other isolates from Mexico (independent from the present study; n = 147), to
      determine any evidence for genetic relatedness between circulating M. bovis
      strains. The results showed that all human M. bovis cases were not genetically
      related between them or to any bovine strain. Interestingly, a high degree of
      genetic variability was observed among bovine strains. Several autochthonous and
      presumably imported strains were identified. The emergence of drug-resistant M.
      bovis is an important public health problem that jeopardizes the success of TB
      control programs in the region. 

PMID- 26299907
TI  - Discovery of novel lysine E-aminotransferase inhibitors: An intriguing potential
      target for latent tuberculosis.
AB  - Mycobacterium tuberculosis (MTB) has remarkable ability to persist in the human
      host and causes latent infection in one third of the world population. Currently
      available tuberculosis (TB) drugs while effective in killing actively growing
      MTB, is largely ineffective in killing persistent or latent MTB. Lysine-E
      aminotransferase (LAT) enzyme is reported to be highly up-regulated (41.86 times)
      in in vitro models of TB designed to mimic the latent stage. Hence inhibition of
      this MTB LAT seems attractive for developing novel drugs against latent TB. In
      the present study, crystal structure of the MTB LAT bound to substrate was used
      as a framework for structure-based design utilizing database compounds to
      identify novel thiazole derivative as LAT inhibitors. Thirty six compounds were
      synthesized and evaluated in vitro for their ability to inhibit LAT, in vitro
      activity against latent MTB, in vivo activity using Mycobacterium marinum
      infected zebra fish and cytotoxicity as steps toward the derivation of structure
      activity relationship (SAR) for lead optimization. Compound 4-methoxy-2-(pyridin
      4-yl)thiazole-5-carboxylic acid (24) emerged as the most promising lead with an
      IC50 of 1.22 +/- 0.85 MUM against LAT and showed 2.8 log reduction against
      nutrient starved MTB, with little cytotoxicity at a higher concentration (>50
      MUM). It also exhibited 1.5 log reduction of M. marinum load in in vivo zebra
      fish model at 10 mg/kg. 

PMID- 26299908
TI  - [Language acquisition in preterm infants during the first year of life].
AB  - Previous studies have shown that preterm children are at a higher risk for
      cognitive and language delays than full-term children. Most of these studies have
      concentrated on the effects of prematurity during the preschool or school years,
      while the effect of preterm birth on the early development of language, much of
      which occurs during the first year of life, remains very little explored. This
      article focuses on this crucial period and reviews the studies that have explored
      early phonological and lexical development in preterm infants. The results of
      these studies show uneven proficiency in different language subdomains in preterm
      infants. This raises the possibility that different constraints apply to the
      acquisition of different linguistic subcomponents in this population, in part as
      a result of a complex interaction between maturation, experience, and language
      subdomains. 

PMID- 26299909
TI  - [Social inequalities in perinatal health].
AB  - Social insecurity is a known perinatal risk factor but beyond that, a social
      gradient in perinatal health is observable. This social gradient is particularly
      visible for the risk of neonatal mortality from congenital anomalies, premature
      delivery, and low birth weight. Analysis of mechanisms that would explain how the
      different dimensions of the social status of women interact with perinatal health
      indicators are not to this day fully understood. However, numbers of intermediate
      factors related to both the social status and perinatal risk have been
      identified. Among them, smoking, drug use, exposure to psychological and physical
      stress, genital infections, access to care, or drudgery. Finally, it was observed
      that the interaction of social conditions with the level of maternal education,
      geographic or ethnic origin, and the environment in which women live are complex
      and make the generalization of data obtained in a particular context sensitive. 

PMID- 26299910
TI  - [Bacteriology of early neonatal infection in Brazzaville (Congo)].

PMID- 26299911
TI  - [Deep vein thrombosis due to protein C deficiency in a neonate].
AB  - INTRODUCTION: Venous thromboembolic disease is increasingly recognized as an
      important cause of morbidity and mortality in children. In the neonatal period,
      thrombotic accidents suggest constitutional abnormalities of homeostasis,
      including congenital protein C deficiency. We report on a clinical case that
      helps review all the diagnostic elements and discuss actions to be taken in the
      neonatal period. OBSERVATION: A newborn infant was admitted for transient
      neonatal respiratory distress. The physical examination revealed a facial
      dysmorphism and a bilateral lumbar contact. Abdominal Doppler ultrasounds showed
      a thrombosis of the vena cava inferior and of the left renal vein. Investigations
      searching for a thrombophilic state revealed severe congenital protein C
      deficiency. The maternal level of protein C at 50% argues in favor of a
      heterozygote deficit, the rate being normal in the father. Therapeutic management
      was based on low-molecular-weight heparin. The ultrasound check showed regression
      and then disappearance of thrombosis. Genetic counseling was planned. DISCUSSION
      AND CONCLUSION: In cases of neonatal thrombosis, seeking a deficiency
      anticoagulant factor, in particular of protein C, is essential in the newborn and
      in both parents. Therapeutic management is not codified. An individualized
      approach is appropriate in this very rare clinical situation.

PMID- 26299912
TI  - [Paracetamol (acetaminophen) use in neonatology: a (re)appreciation of an old
      drug].
AB  - In neonates, paracetamol is mainly used for its analgesic action. This drug is
      actually preferred by neonatologists because of its broad therapeutic index.
      Recently, it has been demonstrated that paracetamol is also an anti
      cyclooxygenase (COX) medication through its inhibitory action on the peroxidase
      arm of central and peripheral COX (Boutaud et al., 2002; Toussaint et al., 2010;
      Graham et al., 2013; Hinz et al., 2008; Hinz and Brune, 2011). As such, this drug
      interferes with the synthesis of prostaglandins. This inhibition of peroxidase
      is, however, limited to a low concentration of arachidonic acid (AA) (around
      2MUM, in vitro) when the plasmatic concentration of paracetamol is experimentally
      10MUM, actually within the same range as compared to the therapeutic
      concentrations in vivo. This may partly explain its low anti-inflammatory effect
      as compared to ibuprofen and indomethacin, which exert their inhibition on COX
      whatever the AA concentrations are. This new well-demonstrated action of
      paracetamol on peripheral COX-2 of intact cells could explain recent observations
      making this drug a potential alternative in treating patent ductus arteriosus.
      However, the higher dosages that have been claimed by some authors in this
      indication still remain to be validated. This inhibition that paracetamol shows
      on the physiological synthesis of prostaglandins E2 (PGE2) could also explain
      some long-term immune deviations because the physiological concentration of PGE2
      is a well-known actor in the genesis of immune homeostasis in the submucosal
      area. Indeed, recent epidemiology studies have pointed out immune deviations in
      children repeatedly exposed to paracetamol earlier in life. Consequently, this is
      actually the new discovery of an old drug. From these new data on paracetamol, a
      more focused pharmacovigilance on the long-term effects of paracetamol repeatedly
      given in the early stage should be urgently initiated. 

PMID- 26299913
TI  - [Early-onset neonatal infection: assessment of professional practices in 14
      maternity wards in the Ile-de-France region in 2013].
AB  - INTRODUCTION: Early-onset neonatal infection remains a major cause of morbidity
      and mortality in neonates. Both universal vaginal screening for group-B
      streptococcus (GBS) and intrapartum antibiotic prophylaxis have decreased the
      incidence of early-onset GBS disease. Almost 12 years after the implementation of
      the French recommendations, we assessed the practices around screening,
      diagnosis, and treatment of early-onset neonatal infection in the Ile-de-France
      region. PATIENTS AND METHODS: We conducted a prospective, multicenter,
      observational study in 14 volunteer maternity wards from 18 to 31 March 2013. All
      live newborn infants delivered at 35 gestational weeks or more were eligible.
      Maternal, obstetrical, and neonatal characteristics were collected, as well as
      the management of suspected early-onset neonatal infections. RESULTS: A total of
      1194 mothers and 1217 neonates were included. Among the latter, 54% had
      bacteriological samplings at birth, with at least a gastric aspirate.
      Bacteriological samples were collected at birth in 85% of cases based on major or
      minor anamnestic infection criteria defined by the French National Authority for
      Health in 2002. In addition, 26% of neonates had at least one blood sample taken.
      Antibiotic treatment was administered in 4% of the infants with cefotaxime
      administered in two thirds of cases. CONCLUSION: An update of the French
      guidelines for the management of early-onset neonatal infections is required in
      order to improve targeting of newborn infants suspected of having an infection
      and to optimize the antibiotics administered. Moreover, the role of
      bacteriological sampling at birth needs to be clarified.

PMID- 26299914
TI  - Echocardiography and Cardiac Rupture: Is Contrast Extravasation an Indication for
      Surgery?
AB  - Contrast echocardiography demonstrating microbubbles in the pericardial space has
      often been cited as evidence of ventricular rupture requiring emergent surgical
      intervention. We report a case where no myocardial perforation was found during
      post-myocardial infarction surgery despite prior echocardiographic evidence of
      contrast extravasation into the pericardial effusion. Clinical decision making
      requires balancing imaging evidence with clinical circumstances to determine the
      optimal timing for surgical intervention. 

PMID- 26299915
TI  - 'Button type' bipolar plasma vaporisation of the prostate compared with standard
      transurethral resection: a systematic review and meta-analysis of short-term
      outcome studies.
AB  - OBJECTIVE: To evaluate the surgical morbidity and effectiveness in improving
      symptoms of benign prostatic hyperplasia (BPH), comparing 'button-type' bipolar
      plasma vaporisation (BTPV) vs transurethral resection of the prostate (TURP).
      METHODS: We conducted a literature search of published articles until November
      2014. Only prospective and randomised studies with comparative data between BTPV
      and conventional TURP (mono- or bipolar) were included in this review. RESULTS:
      Six articles were selected for the analyses. In the 871 patients evaluated, 522
      underwent TURP and 349 BTPV. There was a tendency for a higher transfusion rate
      in the TURP group, with two BTPV cases (0.006%) and 16 TURP cases (0.032%)
      requiring transfusions (P = 0.06). The number of complications was similar
      between the groups (odds ratio 0.33, 95% confidence interval [CI] 0.8-1.31; P =
      0.12; I(2) = 86%). When subdivided by severity, 10.7% (14/131) and 14.6% (52/355)
      of complications were classified as severe (Clavien 3 or 4) in patients who
      underwent BTPV and TURP, respectively (P = 0.02). The average duration of
      indwelling catheterisation was significantly less in patients who underwent BTPV
      (standardised mean difference [SMD] -0.84; 95% CI -1.54 to 0.14; P = 0.02; I(2) =
      81%). Both treatments significantly improved symptoms and the postoperative
      International Prostate Symptom Score was similar in both groups (SMD 0.09, 95% CI
      -1.56 to 1.73; P = 0.92). CONCLUSION: BTPV is an effective and safe treatment for
      BPH. The improvement of urinary symptoms and overall complications are comparable
      to conventional TURP. However, BTVP appears to be associated with a lower rate of
      major complications and duration of indwelling catheterisation.

PMID- 26299916
TI  - Mastl/PP2A regulate Cdk1 in ooycte maturation.

PMID- 26299917
TI  - FPRs: linking innate immune system and fibrosis.

PMID- 26299918
TI  - Bmk-1 regulates lifespan in Caenorhabditis elegans by activating hsp-16.
AB  - The genetics of aging is typically concerned with lifespan determination that is
      associated with alterations in expression levels or mutations of particular
      genes. Previous reports in C. elegans have shown that the bmk-1 gene has
      important functions in chromosome segregation, and this has been confirmed with
      its mammalian homolog, KIF11. However, this gene has never been implicated in
      aging or lifespan regulation. Here we show that the bmk-1 gene is an important
      lifespan regulator in worms. We show that reducing bmk-1 expression using RNAi
      shortens worm lifespan by 32%, while over-expression of bmk-1 extends worm
      lifespan by 25%, and enhances heat-shock stress resistance. Moreover, bmk-1 over
      expression increases the level of hsp-16 and decreases ced-3 in C. elegans.
      Genetic epistasis analysis reveals that hsp-16 is essential for the lifespan
      extension by bmk-1. These findings suggest that bmk-1 may act through enhanced
      hsp-16 function to protect cells from stress and inhibit the apoptosis pathway,
      thereby conferring worm longevity. Though it remains unclear whether this is a
      distinct function from chromosomal segregation, bmk-1 is a potential new target
      for extension of lifespan and enhancement of healthspan. 

PMID- 26299919
TI  - Evidence for the involvement of sphingosine-1-phosphate in the homing and
      engraftment of hematopoietic stem cells to bone marrow.
AB  - The alpha-chemokine stromal-derived factor 1 (SDF-1), which binds to the CXCR4
      receptor, directs migration and homing of CXCR4+ hematopoietic stem/progenitor
      cells (HSPCs) to bone marrow (BM) stem cell niches. Nevertheless, it is also
      known that CXCR4-/- fetal liver-derived hematopoietic stem cells engraft into BM
      and that blockade of CXCR4 by its antagonist AMD3100 does not prevent engraftment
      of HSPCs. Because of this finding of SDF-1-CXCR4-independent BM homing, the
      unique role of SDF-1 in HSPC homing has recently been challenged. While SDF-1 is
      the only chemokine that chemoattracts HSPCs, other chemoattractants for these
      cells have recently been described, including the bioactive phosphosphingolipid
      sphingosine-1-phosphate (S1P). To address the potential role of S1P in homing of
      HSPCs to BM, we performed hematopoietic transplants into mice deficient in BM
      expressed sphingosine kinase 1 (Sphk1-/-) using hematopoietic cells from normal
      control mice as well as cells from mice in which floxed CXCR4 (CXCR4fl/fl) was
      conditionally deleted. We observed the presence of a homing and engraftment
      defect in HSPCs of Sphk1-/- mice that was particularly profound after
      transplantation of CXCR4-/- BM cells. Thus, our results indicate that BM
      microenvironment-expressed S1P plays a role in homing of HSPCs. They also support
      the concept that, in addition to the SDF-1-CXCR4 axis, other chemotactic axes are
      also involved in homing and engraftment of HSPCs. 

PMID- 26299920
TI  - Inhibition of microRNA-497 ameliorates anoxia/reoxygenation injury in
      cardiomyocytes by suppressing cell apoptosis and enhancing autophagy.
AB  - MiR-497 is predicted to target anti-apoptosis gene Bcl2 and autophagy gene
      microtubule-associated protein 1 light chain 3 B (LC3B), but the functional
      consequence of miR-497 in response to anoxia/reoxygenation (AR) or
      ischemia/reperfusion (IR) remains unknown. This study was designed to investigate
      the influences of miR-497 on myocardial AR or IR injury. We noted that miR-497
      was enriched in cardiac tissues, while its expression was dynamically changed in
      murine hearts subjected to myocardial infarction and in neonatal rat
      cardiomyocytes (NRCs) subjected to AR. Forced expression of miR-497 (miR-497
      mimic) induced apoptosis in NRCs as determined by Hoechst staining and TUNEL
      assay. In response to AR, silencing of miR-497 using a miR-497 sponge
      significantly reduced cell apoptosis and enhanced autophagic flux. Furthermore,
      the infarct size induced by IR in adenovirus (Ad)-miR-497 sponge infected mice
      was significantly smaller than in mice receiving Ad-vector or vehicle treatment,
      while Ad-miR-497 increased infarct size. The expression of Bcl-2 and LC3B-II in
      NRCs or in murine heart was significantly decreased by miR-497 mimic and enhanced
      by miR-497 sponge. These findings demonstrate that inhibition of miR-497 holds
      promise for limiting myocardial IR injury. 

PMID- 26299921
TI  - Integration of microarray analysis into the clinical diagnosis of hematological
      malignancies: How much can we improve cytogenetic testing?
AB  - PURPOSE: To evaluate the clinical utility, diagnostic yield and rationale of
      integrating microarray analysis in the clinical diagnosis of hematological
      malignancies in comparison with classical chromosome karyotyping/fluorescence in
      situ hybridization (FISH). METHODS: G-banded chromosome analysis, FISH and
      microarray studies using customized CGH and CGH+SNP designs were performed on 27
      samples from patients with hematological malignancies. A comprehensive comparison
      of the results obtained by three methods was conducted to evaluate benefits and
      limitations of these techniques for clinical diagnosis. RESULTS: Overall, 89.7%
      of chromosomal abnormalities identified by karyotyping/FISH studies were also
      detectable by microarray. Among 183 acquired copy number alterations (CNAs)
      identified by microarray, 94 were additional findings revealed in 14 cases (52%),
      and at least 30% of CNAs were in genomic regions of diagnostic/prognostic
      significance. Approximately 30% of novel alterations detected by microarray were
      >20 Mb in size. Balanced abnormalities were not detected by microarray; however,
      of the 19 apparently "balanced" rearrangements, 55% (6/11) of recurrent and 13%
      (1/8) of non-recurrent translocations had alterations at the breakpoints
      discovered by microarray. CONCLUSION: Microarray technology enables accurate,
      cost-effective and time-efficient whole-genome analysis at a resolution
      significantly higher than that of conventional karyotyping and FISH. Array-CGH
      showed advantage in identification of cryptic imbalances and detection of clonal
      aberrations in population of non-dividing cancer cells and samples with poor
      chromosome morphology. The integration of microarray analysis into the
      cytogenetic diagnosis of hematologic malignancies has the potential to improve
      patient management by providing clinicians with additional disease specific and
      potentially clinically actionable genomic alterations.

PMID- 26299922
TI  - MiR-139-5p inhibits the biological function of breast cancer cells by targeting
      Notch1 and mediates chemosensitivity to docetaxel.
AB  - OBJECTIVES: MiRNA-139 is located at 11q13.4 and it has anti-oncogenic and
      antimetastatic activity in humans. However, its role in controlling apoptosis,
      invasion and metastasis and the development of chemosensitivity to docetaxel in
      breast cancer cells are not fully understood. The aim of this study was to
      research the biological function of miR-139-5p and the efficacy of
      chemosensitivity to docetaxel. METHODS: MiR-139-5p expression in MCF-7, MCF-7/Doc
      cells and in selected breast cancer tissue samples was confirmed by real-time
      PCR; cell viability was analyzed by Cell Counting Kit-8 assay; apoptosis and cell
      cycle were analyzed by flow cytometry; control of metastasis and invasion of
      breast cancer cells was measured by transwell assay; expression of Notch1 was
      measured by western blot; a luciferase reporter vector was constructed to
      identify the miR-139-5p target gene. RESULTS: MiR-139-5p was significantly down
      regulated in breast cancer cells. MiR-139-5p inhibits the viability of breast
      cancer cells. MiR-139-5p induces apoptosis, causes cell cycle arrest in S phase,
      inhibits migration and invasion in breast cancer cells, however, MiR-139-5p play
      the opposite role in docetaxel-induced breast cancer cells. CONCLUSIONS: MiR-139
      5p not only attenuated the development of breast cancer cells but also mediated
      drug-resistance by regulating the expression of the downstream target gene
      Notch1.

PMID- 26299923
TI  - Crystal structure of Staphylococcus aureus exfoliative toxin D-like protein:
      Structural basis for the high specificity of exfoliative toxins.
AB  - Exfoliative toxins are serine proteases secreted by Staphylococcus aureus that
      are associated with toxin-mediated staphylococcal syndromes. To date, four
      different serotypes of exfoliative toxins have been identified and 3 of them
      (ETA, ETB, and ETD) are linked to human infection. Among these toxins, only the
      ETD structure remained unknown, limiting our understanding of the structural
      determinants for the functional differentiation between these toxins. We recently
      identified an ETD-like protein associated to S. aureus strains involved in mild
      mastitis in sheep. The crystal structure of this ETD-like protein was determined
      at 1.95 A resolution and the structural analysis provide insights into the
      oligomerization, stability and specificity and enabled a comprehensive structural
      comparison with ETA and ETB. Despite the highly conserved molecular architecture,
      significant differences in the composition of the loops and in both the N- and C
      terminal alpha-helices seem to define ETD-like specificity. Molecular dynamics
      simulations indicate that these regions defining ET specificity present different
      degrees of flexibility and may undergo conformational changes upon substrate
      recognition and binding. DLS and AUC experiments indicated that the ETD-like is
      monomeric in solution whereas it is present as a dimer in the asymmetric unit
      indicating that oligomerization is not related to functional differentiation
      among these toxins. Differential scanning calorimetry and circular dichroism
      assays demonstrated an endothermic transition centered at 52  degrees C, and an
      exothermic aggregation in temperatures up to 64  degrees C. All these together
      provide insights about the mode of action of a toxin often secreted in syndromes
      that are not associated with either ETA or ETB. 

PMID- 26299924
TI  - NFAT5 promotes proliferation and migration of lung adenocarcinoma cells in part
      through regulating AQP5 expression.
AB  - The osmoregulated transcription factor nuclear factor of activated T-cells
      5(NFAT5), has been found to play important roles in the development of many kinds
      of human cancers, including breast cancer, colon carcinoma, renal cell carcinoma
      and melanoma. The aim of the present study was to determine whether NFAT5 is
      involved in the proliferation and migration of lung adenocarcinoma cells. We
      found that NFAT5 was upregulated in lung adenocarcinoma cells and knockdown of
      NFAT5 decreased proliferation and migration of the cells, accompanied by a
      significant reduction in the expression of AQP5. AQP5 was upregulated in lung
      adenocarcinoma cells and knockdown of AQP5 also inhibited proliferation and
      migration of the cells as knockdown of NFAT5 did. Moreover, overexpression of
      NFAT5 promoted proliferation and migration of lung adenocarcinoma cells,
      accompanied by a significant increase in the expression of AQP5. These results
      indicate that NFAT5 plays important roles in proliferation and migration of human
      lung adenocarcinoma cells through regulating AQP5 expression, providing a new
      therapeutic option for lung adenocarcinoma therapy. 

PMID- 26299926
TI  - Tsukushi expression is dependent on Notch signaling and oscillated in the
      presomitic mesoderm during chick somitogenesis.
AB  - During somitogenesis, segmentation of the body axis occurs by epithelial somites
      budding off from the rostral end of the unsegmented presomitic mesoderm (PSM),
      and its molecular regulation is achieved by a molecular oscillator and signaling
      molecules. Tsukushi (TSK) is a unique secreted protein and involved in diverse
      biological cascades in vertebrate embryos by modulating several signaling
      pathways at the extracellular region. However, the involvement of TSK in
      somitogenesis remains unknown. In this study, we investigated the detailed
      expression patterns of TSK at different developmental stages of a chick embryo.
      Chick-TSK (C-TSK) is expressed in the PSM and shows an oscillation pattern with
      three phases. The oscillation pattern of C-TSK in the PSM is similar to that of c
      Notch1 and c-hairy1, but not to c-Delta1. Our in vitro data showed that Notch
      signaling is necessary for the normal expression of C-TSK and that expression of
      C-TSK is an intrinsic property of the anterior PSM. These data suggest that TSK
      plays a role in chick somitogenesis.

PMID- 26299925
TI  - A potential link between insulin signaling and GLUT4 translocation: Association
      of Rab10-GTP with the exocyst subunit Exoc6/6b.
AB  - Insulin increases glucose transport in fat and muscle cells by stimulating the
      exocytosis of specialized vesicles containing the glucose transporter GLUT4. This
      process, which is referred to as GLUT4 translocation, increases the amount of
      GLUT4 at the cell surface. Previous studies have provided evidence that insulin
      signaling increases the amount of Rab10-GTP in the GLUT4 vesicles and that GLUT4
      translocation requires the exocyst, a complex that functions in the tethering of
      vesicles to the plasma membrane, leading to exocytosis. In the present study we
      show that Rab10 in its GTP form binds to Exoc6 and Exoc6b, which are the two
      highly homologous isotypes of an exocyst subunit, that both isotypes are found in
      3T3-L1 adipocytes, and that knockdown of Exoc6, Exoc6b, or both inhibits GLUT4
      translocation in 3T3-L1 adipocytes. These results suggest that the association of
      Rab10-GTP with Exoc6/6b is a molecular link between insulin signaling and the
      exocytic machinery in GLUT4 translocation. 

PMID- 26299927
TI  - Exendin-4 protects hindlimb ischemic injury by inducing angiogenesis.
AB  - Exendin-4, an analog of glucagon-like peptide-1, has shown to have beneficial
      effects on endothelial function, and was recently approved for the treatment of
      diabetes. In previous studies, we showed that exendin-4 induces angiogenesis in
      in vitro and ex vivo assays; in this study, we assessed the proangiogenic effects
      of exendin-4 in vivo using a mouse hindlimb ischemia model. Treatment with
      exendin-4 for three days mitigated hindlimb and gastrocnemius muscle fiber
      necrosis. Hindlimb perfusion was determined using indocyanine green fluorescence
      dynamics that showed, significantly higher blood flow rate to the ischemic
      hindlimbs in an exendin-4-treated group. Immunohistochemistry assay showed that
      exendin-4 increased CD31-positive areas in the gastrocnemius muscle of ischemic
      limbs. Furthermore, treatment of the hindlimbs of ischemic mice with exendin-4
      increased vascular endothelial growth factor (VEGF) and phospho-extracellular
      signal-related kinase (ERK) on western blot analysis. Our data demonstrate that
      exendin-4 prevents hindlimb ischemic injury by inducing vessels via VEGF
      angiogenic-related pathways. These findings suggest that exendin-4 has potential
      as a therapeutic agent for vascular diseases that stimulate angiogenesis.

PMID- 26299928
TI  - Trehalose intake induces chaperone molecules along with autophagy in a mouse
      model of Lewy body disease.
AB  - The accumulation of mis-folded and/or abnormally modified proteins is a major
      characteristic of many neurodegenerative diseases. In Lewy body disease (LBD),
      which includes Parkinson's disease and dementia with Lewy bodies, insoluble alpha
      synuclein is widely deposited in the presynaptic terminals as well as in the
      neuronal cytoplasm in distinct brain regions. It is well known that the autophagy
      lysosome system serves as an efficient degradation pathway for abnormal molecules
      within cells. To test the possibility that activated autophagy can degrade
      abnormal molecules, we investigated the effect of trehalose on abnormal
      aggregation of alpha-synuclein in a model of LBD. Trehalose is a natural
      disaccharide composed of two glucose units and functions as an autophagy inducer.
      Consistent with previous studies, trehalose increased level of the autophagosomal
      protein LC3, especially a lipidated form LC3-II in cultured cells and mice brain.
      Also, trehalose increased levels of several chaperon molecules, such as HSP90 and
      SigmaR1, in the brains of LBD model mice. Further studies revealed that level of
      detergent-insoluble alpha-synuclein was suppressed in mice following oral
      administration of trehalose, despite an apparent alteration was not observed
      regarding abnormal aggregation of alpha-synuclein. These results suggest that the
      oral intake of trehalose modulates propensity of molecules prior to aggregation
      formation.

PMID- 26299929
TI  - Development of a screening method to identify regulators of MICA shedding.
AB  - Immune cells, such as natural killer (NK) cells, recognize virally infected and
      transformed cells, and eliminate them through the interaction between NKG2D
      receptors on NK cells and NKG2D ligands on pathogenic cells. Shedding of NKG2D
      ligands is thought to be a type of counter-mechanism employed by pathogenic cells
      to evade from NKG2D-mediated immune surveillance. MHC class I polypeptide-related
      sequence A (MICA) is a prototypical NKG2D ligand. We previously reported that, in
      soluble form, MICA expression levels are significantly associated with hepatitis
      virus-induced hepatocellular carcinoma. Here, we report a MICA shedding assay
      that utilizes membrane-bound MICA tagged at its N-terminus with a nano-luciferase
      reporter to quantify MICA shedding into culture media. Using this method, we
      screened a compound library and identified putative regulators of MICA shedding
      that have the potential to enhance the immune reaction by simultaneously
      increasing cell surface MICA levels and decreasing soluble MICA levels. This
      shedding assay may be useful for screening regulators of cell surface molecule
      shedding.

PMID- 26299930
TI  - Influence of GTP on system specific chaperone - Twin arginine signal peptide
      interaction.
AB  - Many bacterial respiratory redox enzymes depend on the twin-arginine translocase
      (Tat) system for translocation and membrane insertion. Tat substrates contain an
      N-terminal twin-arginine (SRRxFLK) motif serving as the targeting signal towards
      the translocon. Many Tat substrates have a system specific chaperone - redox
      enzyme maturation protein (REMP) - for final folding and assembly prior to Tat
      binding. The REMP DmsD strongly interacts with the twin-arginine motif of the
      DmsA signal sequence of dimethyl sulfoxide (DMSO) reductase. In this study, we
      have utilized the in vitro protein-protein interaction technique of an affinity
      pull down assay, as well as protein thermal stability measurement via
      differential scanning fluorimetry (DSF) to investigate the interaction of
      guanosine nucleotides (GNPs) with DmsD. Here we have shown highly cooperative
      binding of DmsD with GTP. A dissociative ligand-binding style isotherm was
      generated upon GTP titration into the DmsD:DmsAL interaction, yielding sigmoidal
      release of DmsD with a Hill coefficient of 2.09 and a dissociation constant of
      0.99 mM. DSF further illustrated the change in thermal stability upon DmsD
      interaction with DmsAL and GTP. These results imply the possibility of DmsD
      detection and binding of GTP during the DMSO protein maturation mechanism, from
      ribosomal translation to membrane targeting and final assembly. Conceivably, GTP
      is shown to act as a molecular regulator in the biochemical pathway.

PMID- 26299931
TI  - Synergistic effect of fluoride and sodium hexametaphosphate in toothpaste on
      enamel demineralization in situ.
AB  - OBJECTIVE: To evaluate the effect of a fluoride dentifrice containing sodium
      hexametaphosphate (HMP) on enamel demineralization in situ. METHODS: This double
      blind and cross-over study consisted of 3 phases (7 days each) in which 12
      volunteers wore intraoral appliances containing four enamel bovine blocks.
      Specimens were treated (3*/day) with placebo (no F or HMP), 1100ppm F (1100F) and
      1100F plus HMP1% (1100F-HMP1%) toothpastes, and the cariogenic challenge was
      performed using a 30% sucrose solution (6*/day). Final surface hardness, the
      percentage of surface hardness loss (%SH), the integrated loss of subsurface
      hardness (DeltaKHN), as well as enamel calcium (Ca), phosphorus (P) and firmly
      bound fluoride (F) were determined. Also, biofilm formed on the blocks were
      analyzed for F, Ca, P and insoluble extracellular polysaccharide (EPS)
      concentrations. Data were submitted 1-way ANOVA, followed by Student-Newman
      Keuls' test (p<0.05). RESULTS: 1100F-HMP1% promoted the lowest %SH and DeltaKHN
      among all groups (p<0.001). The addition of HMP1% to 1100F did not enhance enamel
      F uptake, but significantly increased enamel Ca concentrations (p<0.001). Similar
      EPS concentrations were seen for 1100F-HMP1% and 1100F groups (p>0.05). All the
      groups were supersaturated with respect to HA. However, only 1100F-HMP1% group
      was supersaturated with respect to CaF2 (p<0.05). The ionic activities of F(-),
      CaF(+) and HF(0) for the 1100F-HMP1% group were the highest among all groups
      (p<0.001). CONCLUSION: The addition of HMP1% to a conventional toothpaste
      significantly reduces enamel demineralization in situ when compared to 1100F.
      CLINICAL RELEVANCE: This dentifrice could be a viable alternative to patients at
      high risk of caries.

PMID- 26299932
TI  - Microbiological consequences of indoor composting.
AB  - Recycling of organic waste appeals to more and more people. The aim of this study
      was to evaluate the microbiological contamination around organic waste bins at
      three distances over a 12-month period. Contamination near the customary trash of
      control households was evaluated at the beginning to ensure that there is no
      recruitment bias. Air samples using the MAS 100 impactor were carried out in 38
      dwellings that do household waste composting and in 10 dwellings of controls.
      Collection of particles by CIP 10 rotating cup sampler and dust samples collected
      by electrostatic dust collector cloths were acquired in dwellings that do
      household waste composting. Samples were analyzed by culture and by real-time
      quantitative PCR. Information about dwelling characteristics and inhabitant
      practices was obtained by a standardized questionnaire. The genera most often
      isolated were Penicillium, Aspergillus, Cladosporium and Streptomyces. Near the
      organic waste bins, bioaerosol samples showed an increase of Acarus siro (P =
      0.001). Sedimented dust analyses highlighted an increase of A. siro, Wallemia
      sebi, Aspergillus versicolor, and Cladosporium sphaerospermum concentrations
      after a 12-month survey compared to the beginning. Composting favors
      microorganism development over time, but does not seem to have an effect on the
      bioaerosol levels and the surface microbiota beyond 0.5 m from the waste bin.

PMID- 26299933
TI  - Improvement of an enzyme immunosorbent assay for detecting antibodies against
      Dioctophyma renale.
AB  - An available enzyme-linked immunosorbent assay (ELISA) was studied for the
      detection of anti-Dioctophyma renale antibodies in the sera of dogs using,
      detection of parasite eggs in urine sediment as a reference test. ELISA uses a
      soluble antigenic preparation of esophagus of D. renale and the optimal dilutions
      of the antigen, serum and conjugate were determined by means of checker board
      titration, using positive (n=13) and negative (n=27) reference serum. The
      specificity and sensitivity of the ELISA were 93.8% and 92.3% respectively and
      the kappa index was good (0.76). These results suggest that ELISA described may
      prove to be an effective serological test for detecting dogs infected and exposed
      to this parasite mainly dogs that are not eliminating parasite eggs through their
      urine. 

PMID- 26299934
TI  - Alveolar and cystic echinococcosis in Europe: Old burdens and new challenges.

PMID- 26299935
TI  - Systems biology-based discovery of a potential Atg4B agonist (Flubendazole) that
      induces autophagy in breast cancer.
AB  - The aim of this study was to explore the autophagy-related protein 4B(ATG4B) and
      its targeted candidate agonist in triple-negative breast cancer (TNBC) therapy.
      In this study, the identification of Atg4B as a novel breast cancer target for
      screening candidate small molecular agonists was performed by phylogenetic
      analysis, network construction, molecular modelling, molecular docking and
      molecular dynamics (MD) simulation. In vitro, MTT assay, electron microscopy,
      western blot and ROS measurement were used for validating the efficacy of the
      candidate compounds. We used the phylogenetic analysis of Atg4B and constructed
      their protein-protein interaction (PPI) network. Also, we screened target
      compounds of Atg4 proteins from Drugbank and ZINC. Flubendazole was validated for
      its anti-proliferative efficacy in MDA-MB-231 cells. Further MD simulation
      results supported the stable interaction between Flubendazole and Atg4B.
      Moreover, Flubendazole induced autophagy and increased ROS production. In
      conclusion, in silico analysis and experimental validation together demonstrate
      that Flubendazole can target Atg4B in MDA-MB-231 cells and induce autophagy,
      which may shed light on the exploration of this compound as a potential new Atg4B
      targeted drug for future TNBC therapy. 

PMID- 26299936
TI  - Coronin Enhances Actin Filament Severing by Recruiting Cofilin to Filament Sides
      and Altering F-Actin Conformation.
AB  - High rates of actin filament turnover are essential for many biological processes
      and require the activities of multiple actin-binding proteins working in concert.
      The mechanistic role of the actin filament severing protein cofilin is now firmly
      established; however, the contributions of other conserved disassembly-promoting
      factors including coronin have remained more obscure. Here, we have investigated
      the mechanism by which yeast coronin (Crn1) enhances F-actin turnover. Using
      multi-color total internal reflection fluorescence microscopy, we show that Crn1
      enhances Cof1-mediated severing by accelerating Cof1 binding to actin filament
      sides. Further, using biochemical assays to interrogate F-actin conformation, we
      show that Crn1 alters longitudinal and lateral actin-actin contacts and restricts
      opening of the nucleotide-binding cleft in actin subunits. Moreover, Crn1 and
      Cof1 show opposite structural effects on F-actin yet synergize in promoting
      release of phalloidin from filaments, suggesting that Crn1/Cof1 co-decoration may
      increase local discontinuities in filament topology to enhance severing. 

PMID- 26299937
TI  - Structural Insights into Nonspecific Binding of DNA by TrmBL2, an Archaeal
      Chromatin Protein.
AB  - The crystal structure of TrmBL2 from the archaeon Pyrococcus furiosus shows an
      association of two pseudosymmetric dimers. The dimers follow the prototypical
      design of known bacterial repressors with two helix-turn-helix (HTH) domains
      binding to successive major grooves of the DNA. However, in TrmBL2, the two
      dimers are arranged at a mutual displacement of approximately 2bp so that they
      associate with the DNA along the double-helical axis at an angle of approximately
      80 degrees . While the deoxyribose phosphate groups of the double-stranded DNA
      (dsDNA) used for co-crystallization are clearly seen in the electron density map,
      most of the nucleobases are averaged out. Refinement required to assume a
      superposition of at least three mutually displaced dsDNAs. The HTH domains
      interact primarily with the deoxyribose phosphate groups and polar interactions
      with the nucleobases are almost absent. This hitherto unseen mode of DNA binding
      by TrmBL2 seems to arise from nonoptimal protein-DNA contacts made by its four
      HTH domains resulting in a low-affinity, nonspecific binding to DNA. 

PMID- 26299939
TI  - Chirality control of nonplanar lead phthalocyanine (PbPc) and its potential
      application in high-density storage: a theoretical investigation.
AB  - On single-crystal surfaces, achiral molecules may become chiral owing to
      confinement in two dimensions (2D). Metal phthalocyanines (MPcs) on Cu(001) and
      Ag(100) surfaces have exhibited a chiral electronic state. However, the chirality
      is not always desirable since crystal defects (grain boundaries) inevitably occur
      between two different chiral domains during the self-assembly of single layers.
      In this theoretical study, we propose to utilize metal(001) substrates with
      different electron configurations to mediate the azimuthal orientations of
      nonplanar PbPc. The results show that PbPc is chiral on Cu(001) with a partially
      filled s orbital (3d(10)4s(1)) but achiral on Pd(001) with a completely filled d
      orbital (4d(10)). The mechanism that PbPc prefers achiral azimuthal orientation
      rather than chiral orientation on Pd(001) is clarified. In addition, we predict
      that PbPc can form a (3 * 4) surface reconstruction. While it is used for data
      storage, the capacity is almost three orders of magnitude higher than the present
      storage materials. 

PMID- 26299938
TI  - Activation of sonic hedgehog signaling enhances cell migration and invasion by
      induction of matrix metalloproteinase-2 and -9 via the phosphoinositide-3
      kinase/AKT signaling pathway in glioblastoma.
AB  - Aberrant hedgehog signaling contributes to the development of various
      malignancies, including glioblastoma (GBM). However, the potential mechanism of
      hedgehog signaling in GBM migration and invasion has remained to be elucidated.
      The present study showed that enhanced hedgehog signaling by recombinant human
      sonic hedgehog N-terminal peptide (rhSHH) promoted the adhesion, invasion and
      migration of GBM cells, accompanied by increases in mRNA and protein levels of
      matrix metalloproteinase-2 (MMP-2) and MMP-9. However, inhibition of hedgehog
      signaling with cyclopamine suppressed the adhesion, invasion and migration of GBM
      cells, accompanied by decreases in mRNA and protein levels of MMP-2 and -9.
      Furthermore, it was found that MMP-2- and MMP-9-neutralizing antibodies or
      GAM6001 reversed the inductive effects of rhSHH on cell migration and invasion.
      In addition, enhanced hedgehog signaling by rhSHH increased AKT phosphorylation,
      whereas blockade of hedgehog signaling decreased AKT phosphorylations. Further
      experiments showed that LY294002, an inhibitor of phosphoinositide-3 kinase
      (PI3K), decreased rhSHH-induced upregulation of MMP-2 and -9. Finally, the
      protein expression of glioblastoma-associated oncogene 1 was positively
      correlated with levels of phosphorylated AKT as well as protein expressions of
      MMP-2 and -9 in GBM tissue samples. In conclusion, the present study indicated
      that the hedgehog pathway regulates GBM-cell migration and invasion by increasing
      MMP-2 and MMP-9 production via the PI3K/AKT pathway.

PMID- 26299940
TI  - Identification of immunodominant Leishmania major antigenic markers of the early
      C57BL/6 and BALB/c mice infection stages.
AB  - The C57BL/6 mouse strain is resistant to Leishmania (L.) major infection and,
      unlike susceptible BALB/c, develops small self-healing cutaneous lesions. The
      specific antibody responses of C57BL/6 and BALB/c mice were previously
      characterized by the predominance of IgG2a ('resistant' isotype associated with
      Th1) and IgG1 ('pathogenic' isotype associated with Th2) antibodies,
      respectively. In this study, we looked for the presence of antigens able to
      elicit an exclusive or predominant IgG1 production during the early stages of
      C57BL/6 lesion development and checked whether they are recognized or not by
      BALB/c mice. We demonstrate first that IgG2a predominance in C57BL/6 sera occurs
      only late after infection, whereas in BALB/c, IgG1 antibodies dominate mostly in
      the early stages. Interestingly, soon after inoculation of live amastigotes,
      C57BL/6 displayed an exclusive IgG1 reactivity against particular L. major
      antigens but with MWs different from those identified in BALB/c. Furthermore,
      mice immunized with killed amastigotes displayed striking differences in their
      immunodetection profiles, particularly for the IgG1 isotype. Taken together, the
      observed differences in the specific antibody repertoires between infected mice
      resulted, at least in part, from immunological events independent from those
      triggered by the replicating parasite, and bring new insights into the selection
      of future vaccine candidates.

PMID- 26299941
TI  - Prey composition and ontogenetic shift in coastal populations of longnose gar
      Lepisosteus osseus.
AB  - Longnose gar Lepisosteus osseus were collected from May 2012 to July 2013 in the
      Charleston Harbor and Winyah Bay estuaries (SC, U.S.A.). This study examined
      trends in stomach fullness, described major prey components and their importance
      in the diet of L. osseus, compared stomach content-based trophic level estimates
      with the stable-isotope-based proxy: delta(15) N and tested for the occurrence of
      an ontogenetic diet shift using stomach content analysis and stable C and N
      isotopes (delta(13) C and delta(15) N). Dominant prey families were Clupeidae,
      Sciaenidae, Penaeidae, Fundulidae and Mugilidae, with the highest consumption
      rates in autumn. Trophic levels calculated using stomach contents did not
      correspond to delta(15) N (P > 0.05). Stomach contents and stable-isotope
      signatures indicate ontogenetic prey composition shifts from low trophic level
      benthic prey (fundulids) to higher trophic level pelagic prey (clupeids) as the
      fish grow between 400 and 600 mm in standard length. Due to their biomass,
      abundance and top predator status, L. osseus play a significant ecological role
      in the estuarine community composition, although this effect has often been
      overlooked by past researchers and should be considered in future estuarine
      community studies. 

PMID- 26299942
TI  - Extract of Rhizoma Polygonum cuspidatum reduces early renal podocyte injury in
      streptozotocin-induced diabetic rats and its active compound emodin inhibits
      methylglyoxal-mediated glycation of proteins.
AB  - Podocyte injury contributes to renal damage and, eventually, to the occurrence of
      proteinuria in diabetic nephropathy. The aim of the present study was to
      investigate the effect of an ethanol extract from Rhizoma Polygonum cuspidatum
      (P. cuspidatum) on proteinuria and podocyte injury, and elucidate the underlying
      mechanism for streptozotocin (STZ)-induced diabetic nephropathy. The protective
      effects of P. cuspidatum extract (PCE) on renal podocytes in STZ-induced diabetic
      rats were also investigated. PCE (100 or 350 mg/kg/day) was administered to STZ
      induced diabetic rats for 16 weeks, and blood glucose levels, body weight and
      proteinuria were measured. A double labeling technique with the terminal
      deoxynucleotidyl transferase dUTP nick end labeling assay was performed and
      synaptopodin expression was observed. In addition, cleaved caspase-3,
      methylglyoxal (MGO) and 8-hydroxydeoxyguanosine (8-OHdG) expression levels were
      measured. STZ-induced diabetic rats developed hyperglycemia and proteinuria.
      Increased apoptosis of the podocytes and increased cleaved caspase-3, MGO and 8
      OHdG expression levels, as well as decreased synaptopodin expression were
      detected in the glomeruli of STZ-induced diabetic rats. However, treatment with
      PCE for 16 weeks restored protein levels to normal, and reduced podocyte loss and
      apoptosis. Levels of caspase-3 and MGO expression, as well as oxidative stress
      were ameliorated by PCE treatment. In addition, emodin, a biologically active
      ingredient of PCE, exerted an MGO scavenging effect and inhibited MGO-derived
      advanced glycation end-product formation. These findings indicate that PCE may be
      administered to prevent proteinuria and podocyte loss in STZ-induced diabetic
      rats partly by inhibiting podocyte apoptosis and cleaved caspase-3 expression,
      and by restoring the balance of oxidative stress and MGO expression.

PMID- 26299943
TI  - Highlighting Indication of extracorporeal membrane oxygenation in endocrine
      emergencies.
AB  - Extracorporeal membrane oxygenation (ECMO) has been repeatedly used to rescue
      patients with cardiopulmonary arrest. However, its clinical utility in endocrine
      emergencies remains unclear. Herein, we describe a case series of 12 patients
      presenting with refractory shock secondary to endocrine emergencies who were
      rescued by ECMO support. Patients were identified between 2005 and 2012 from our
      ECMO registry. The diagnostic distribution was as follows: pheochromocytoma
      crisis (n = 4), thyroid storm (n = 5), and diabetic ketoacidosis (n = 3). The
      initial presentation of pheochromocytoma crisis was indistinguishable from acute
      myocardial infarction (AMI) and frequently accompanied by paroxysmal hypertension
      and limb ischemia. Thyroid storm was characterized by hyperbilirubinemia and
      severe gastrointestinal bleeding, whereas neurological symptoms were common in
      diabetic ketoacidosis. The clinical outcomes of patients with endocrine
      emergencies were compared with those of 80 cases with AMI who received ECMO
      because of cardiogenic shock. The cardiac function and the general conditions
      showed a significantly faster recovery in patients with endocrine emergencies
      than in those with AMI. We conclude that ECMO support can be clinically useful in
      endocrine emergencies. The screening of endocrine diseases should be considered
      during the resuscitation of patients with refractory circulatory shock. 

PMID- 26299945
TI  - Structure and Switch Cycle of SRbeta as Ancestral Eukaryotic GTPase Associated
      with Secretory Membranes.
AB  - G proteins of the Ras-family of small GTPases trace the evolution of eukaryotes.
      The earliest branching involves the closely related Arf, Sar1, and SRbeta GTPases
      associated with secretory membranes. SRbeta is an integral membrane component of
      the signal recognition particle (SRP) receptor that targets ribosome-nascent
      chain complexes to the ER. How SRbeta integrates into the regulation of SRP
      dependent membrane protein biogenesis is not known. Here we show that SRbeta-GTP
      interacts with ribosomes only in presence of SRalpha and present crystal
      structures of SRbeta in complex with the SRX domain of SRalpha in the GTP-bound
      state at 3.2 A, and of GDP- and GDP . Mg(2+)-bound SRbeta at 1.9 A and 2.4 A,
      respectively. We define the GTPase switch cycle of SRbeta and identify specific
      differences to the Arf and Sar1 families with implications for GTPase regulation.
      Our data allow a better integration of SRbeta into the scheme of protein
      targeting.

PMID- 26299944
TI  - Structure of the Human Atg13-Atg101 HORMA Heterodimer: an Interaction Hub within
      the ULK1 Complex.
AB  - The ULK1 complex, consisting of the ULK1 protein kinase itself, FIP200, Atg13,
      and Atg101, controls the initiation of autophagy in animals. We determined the
      structure of the complex of the human Atg13 HORMA (Hop1, Rev7, Mad2) domain in
      complex with the full-length HORMA domain-only protein Atg101. The two HORMA
      domains assemble with an architecture conserved in the Mad2 conformational
      heterodimer and the S. pombe Atg13-Atg101 HORMA complex. The WF finger motif that
      is essential for function in human Atg101 is sequestered in a hydrophobic pocket,
      suggesting that the exposure of this motif is regulated. Benzamidine molecules
      from the crystallization solution mark two hydrophobic pockets that are conserved
      in, and unique to, animals, and are suggestive of sites that could interact with
      other proteins. These features suggest that the activity of the animal Atg13
      Atg101 subcomplex is regulated and that it is an interaction hub for multiple
      partners.

PMID- 26299946
TI  - Solution Structure of Apoptotic BAX Oligomer: Oligomerization Likely Precedes
      Membrane Insertion.
AB  - Proapoptotic BAX protein is largely cytosolic in healthy cells, but it
      oligomerizes and translocates to mitochondria upon receiving apoptotic stimuli. A
      long-standing challenge has been the inability to capture any structural
      information beyond the onset of activation. Here, we present solution structures
      of an activated BAX oligomer by means of spectroscopic and scattering methods,
      providing details about the monomer-monomer interfaces in the oligomer and how
      the oligomer is assembled from homodimers. We show that this soluble oligomer
      undergoes a direct conversion into membrane-inserted oligomer, which has the
      ability of inducing apoptosis and structurally resembles a membrane-embedded
      oligomer formed from BAX monomers in lipid environment. Structural differences
      between the soluble and the membrane-inserted oligomers are manifested in the C
      terminal helices. Our data suggest an alternative pathway of apoptosis in which
      BAX oligomer formation occurs prior to membrane insertion.

PMID- 26299949
TI  - Critical neurocircuitry mediating cardiovascular diseases and strategies for
      intervention.

PMID- 26299947
TI  - Structure of Ribosomal Silencing Factor Bound to Mycobacterium tuberculosis
      Ribosome.
AB  - The ribosomal silencing factor RsfS slows cell growth by inhibiting protein
      synthesis during periods of diminished nutrient availability. The crystal
      structure of Mycobacterium tuberculosis (Mtb) RsfS, together with the cryo
      electron microscopy (EM) structure of the large subunit 50S of Mtb ribosome,
      reveals how inhibition of protein synthesis by RsfS occurs. RsfS binds to the 50S
      at L14, which, when occupied, blocks the association of the small subunit 30S.
      Although Mtb RsfS is a dimer in solution, only a single subunit binds to 50S. The
      overlap between the dimer interface and the L14 binding interface confirms that
      the RsfS dimer must first dissociate to a monomer in order to bind to L14. RsfS
      interacts primarily through electrostatic and hydrogen bonding to L14. The EM
      structure shows extended rRNA density that it is not found in the Escherichia
      coli ribosome, the most striking of these being the extended RNA helix of H54a. 

PMID- 26299948
TI  - The PTEN Tumor Suppressor Forms Homodimers in Solution.
AB  - As the phosphoinositol-3-kinase antagonist in the PI3K pathway, the PTEN tumor
      suppressor exerts phosphatase activity on diacylphosphatidylinositol triphosphate
      in the plasma membrane. Even partial loss of this activity enhances
      tumorigenesis, but a mechanistic basis for this aspect of PTEN physiology has not
      yet been established. It was recently proposed that PTEN mutations have dominant
      negative effects in cancer via PTEN dimers. We show that PTEN forms homodimers in
      vitro, and determine a structural model of the complex from SAXS and Rosetta
      docking studies. Our findings shed new light on the cellular control mechanism of
      PTEN activity. Phosphorylation of the unstructured C-terminal tail of PTEN
      reduces PTEN activity, and this result was interpreted as a blockage of the PTEN
      membrane binding interface through this tail. The results presented here instead
      suggest that the C-terminal tail functions in stabilizing the homodimer, and that
      tail phosphorylation interferes with this stabilization.

PMID- 26299950
TI  - Pemphigoid gestationis revealing a denial of pregnancy.

PMID- 26299951
TI  - WSS25, a sulfated polysaccharide, inhibits RANKL-induced mouse osteoclast
      formation by blocking SMAD/ID1 signaling.
AB  - AIM: WSS25 is a sulfated polysaccharide extracted from the rhizome of Gastrodia
      elata BI, which has been found to bind to bone morphogenetic protein 2 (BMP-2) in
      hepatocellular cancer cells. Since BMP-2 may regulate both osteoclasts and
      osteoblasts, here we investigated the effects of WSS25 on osteoclastogenesis in
      vitro and bone loss in ovariectomized mice. METHODS: RAW264.7 cells or mouse bone
      marrow macrophages (BMMs) were treated with RANKL to induce osteoclastogenesis,
      which was assessed using TRAP staining, actin ring formation and pit formation
      assays, as well as bone resorption assay. Cell viability was detected with MTT
      assay. The mRNA levels of osteoclastogenesis-related genetic markers (TRAP,
      NFATc1, MMP-9 and cathepsin K) were detected using RT-PCR, while the protein
      levels of p-Smad1/5/8 and Id1 were measure with Western blotting. WSS25 was
      administered to ovariectomized mice (100 mg.kg(-1).d(-1), po) for 3 months. After
      the mice were euthanized, total bone mineral density and cortical bone density
      were measured. RESULTS: In RAW264.7 cells and BMMs, WSS25 (2.5, 5, 10 MUg/mL) did
      not affect the cell viability, but dose-dependently inhibited RANKL-induced
      osteoclastogenesis. Furthermore, WSS25 potently suppressed RANKL-induced
      expression of TRAP, NFATc1, MMP-9 and cathepsin K in RAW264.7 cells. Treatment of
      RAW264.7 cells with RANKL increased BMP-2 expression, Smad1/5/8 phosphorylation
      and Id1 expression, which triggered osteoclast differentiation, whereas co
      treatment with WSS25 or the endogenous BMP-2 antagonist noggin suppressed the BMP
      2/Smad/Id1 signaling pathway. In RAW264.7 cells, knockdown of Id1 attenuated
      RANKL-induced osteoclast differentiation, which was partially rescued by Id1
      overexpression. In conformity to the in vitro experiments, chronic administration
      of WSS25 significantly reduced the bone loss in ovariectomized mice. CONCLUSION:
      WSS25 inhibits RANKL-induced osteoclast formation in RAW264.7 cells and BMMs by
      blocking the BMP-2/Smad/Id1 signaling pathway. WSS25 administration reduces bone
      loss in ovariectomized mice, suggesting that it may be a promising therapeutic
      agent for osteoporosis.

PMID- 26299952
TI  - Toward rapamycin analog (rapalog)-based precision cancer therapy.
AB  - Rapamycin and its analogs (rapalogs) are the first generation of mTOR inhibitors,
      which have the same molecular scaffold, but different physiochemical properties.
      Rapalogs are being tested in a wide spectrum of human tumors as both monotherapy
      and a component of combination therapy. Among them, temsirolimus and everolimus
      have been approved for the treatment of breast and renal cancer. However,
      objective response rates with rapalogs in clinical trials are modest and
      variable. Identification of biomarkers predicting response to rapalogs, and
      discovery of drug combinations with improved efficacy and tolerated toxicity are
      critical to moving this class of targeted therapeutics forward. This review
      focuses on the aberrations in the PI3K/mTOR pathway in human tumor cells or
      tissues as predictive biomarkers for rapalog efficacy. Recent results of
      combinational therapy using rapalogs and other anticancer drugs are documented.
      With the rapid development of next-generation genomic sequencing and precision
      medicine, rapalogs will provide greater benefits to cancer patients. 

PMID- 26299953
TI  - Protease Omi cleaving Hax-1 protein contributes to OGD/R-induced mitochondrial
      damage in neuroblastoma N2a cells and cerebral injury in MCAO mice.
AB  - AIM: In the penumbra after focal cerebral ischemia, an increase of protease Omi
      is linked to a decrease of Hs1-associated protein X-1 (Hax-1), a protein
      belonging to the Bcl-2 family. In this study we investigated the mechanisms
      underlying the regulation of Hax-1 by protease Omi in cerebral
      ischemia/reperfusion (I/R) injury. METHODS: Mouse neuroblastoma N2a cells were
      subjected to oxygen-glucose deprivation and reoxygenation (OGD/R); cell viability
      was assessed with MTT assay. Mice underwent 2-h middle cerebral artery occlusion
      (MCAO) and reperfusion, and the infarct volume was determined with TTC staining.
      The expression of Omi and Hax-1 was detected using immunoblot and
      immunofluorescence assays. The mitochondrial membrane potential was measured
      using TMRM staining. RESULTS: In the brains of MCAO mice, the protein level of
      Omi was significantly increased, while the protein level of Hax-1 was decreased.
      Similar changes were observed in OGD/R-treated N2a cells, but the mRNA level of
      Hax-1 was not changed. Furthermore, in OGD/R-treated N2a cells, knockdown of Omi
      significantly increased Hax-1 protein level. Immunofluorescence assay showed that
      Omi and Hax-1 were co-localized in mitochondria of N2a cells. OGD/R caused marked
      mitochondrial damage and apoptosis in N2a cells, while inhibition of Omi protease
      activity with UCF-101 (10 MUmol/L) or overexpression of Hax-1 could restore the
      mitochondrial membrane potential and attenuate cell apoptosis. Moreover,
      pretreatment of MCAO mice with UCF-101 (7.15 mg/kg, ip) could restore Hax-1
      expression, inhibit caspase activation, and significantly reduce the infarct
      volume. CONCLUSION: Protease Omi impairs mitochondrial function by cleaving Hax
      1, which induces apoptosis in OGD/R-treated N2a cells and causes I/R injury in
      MCAO mice.

PMID- 26299955
TI  - Nevoid melanoma: A study of 43 cases with emphasis on growth pattern.
AB  - BACKGROUND: Nevoid melanoma may be confused both clinically and histologically
      with benign nevi. OBJECTIVE: The aim of this study was to characterize the
      histologic features of nevoid melanoma. METHODS: Forty-three cases of nevoid
      melanoma from our laboratory were evaluated. RESULTS: Our study cases included 33
      men and 10 women with mean age of 62 years. The back was the most common site
      followed by the arm. A clinical diagnosis other than melanoma was made in about
      40% of the cases. Two architectural patterns were identified: Plaque and
      polypoid. Sheetlike confluence of melanocytes expanding the papillary dermis was
      seen in 60% of the cases. Nests disposed in parallel arrays at the base of the
      tumor (parallel theque pattern) were present in roughly 81% of our series.
      Mitoses were evident in one-third of cases ranging from less than 1 to 4 per
      square millimeter. Genomic abnormalities characteristic of melanoma were detected
      in 7 of 8 tested cases. LIMITATION: This is a descriptive study. No follow-up
      information was available for 32 of the 43 patients. In the other 11, follow-up
      was limited to the re-excision specimens. CONCLUSION: Characteristic growth
      patterns including confluence of dermal melanocytes with no intervening
      connective tissue and the parallel theque pattern can be helpful in suggesting a
      diagnosis of nevoid melanoma at scanning magnification.

PMID- 26299956
TI  - A Phase 4, Pilot, Open-Label Study of VIVITROL(r) (Extended-Release Naltrexone XR
      NTX) for Prisoners.
AB  - This was a Phase 4, pilot, open-label feasibility study of extended-release
      injectable naltrexone (XR-NTX) administered to pre-release prisoners having a
      history of pre-incarceration opioid disorder. We evaluated the relationship
      between XR-NTX adherence and criminal recidivism (re-arrest and re-incarceration)
      and opioid and cocaine use. Twenty-seven pre-release male and female prisoners
      who had opioid disorders during the year prior to index incarceration were
      recruited and received one XR-NTX injection once each month for 7 months (1
      injection pre-release from prison and 6 injections in the community) and of those
      27, 10 (37%) were retained in treatment at 7-months post release. Results
      indicate those completing 6 compared to those completing <6 injections were less
      likely to test positive for opioids in the community (0% vs. 62.5%, respectively;
      p=0.003). Although not statistically significant, individuals who did not
      complete all 6 injections were more likely to be re-arrested compared to those
      completing all 6 community injections (31.3% vs. 0%, respectively; p=0.123).
      Contingent upon further study of a randomized controlled trial, XR-NTX may be a
      feasible option in the prison setting in view of the lack of potential for
      diversion. Furthermore, these data suggest that completing the entire course of
      treatment (6 injections) may reduce opioid use and, to a lesser degree, re-arrest
      and re-incarceration.

PMID- 26299957
TI  - A review of steroids from Sarcophyton species.
AB  - This review reports the structural diversity of steroids from Sarcophyton species
      based on literature from the beginning of marine steroid research until now.
      There are 65 compounds studied from eight species. Most of them are polyhydroxy
      type steroids of C-27-C-31 carbon skeleton. Their biological activities are
      highly diverse ranging from cytotoxic, antibacterial, antifungal, antiviral, anti
      inflammatory, antidiabetic to antiosteoporosis properties. 

PMID- 26299954
TI  - Genome-wide analysis of microRNA and mRNA expression signatures in cancer.
AB  - Cancer is an extremely diverse and complex disease that results from various
      genetic and epigenetic changes such as DNA copy-number variations, mutations, and
      aberrant mRNA and/or protein expression caused by abnormal transcriptional
      regulation. The expression profiles of certain microRNAs (miRNAs) and messenger
      RNAs (mRNAs) are closely related to cancer progression stages. In the past few
      decades, DNA microarray and next-generation sequencing techniques have been
      widely applied to identify miRNA and mRNA signatures for cancers on a genome-wide
      scale and have provided meaningful insights into cancer diagnosis, prognosis and
      personalized medicine. In this review, we summarize the progress in genome-wide
      analysis of miRNAs and mRNAs as cancer biomarkers, highlighting their diagnostic
      and prognostic roles. 

PMID- 26299958
TI  - Improvement in clinical outcome of FLT3 ITD mutated acute myeloid leukemia
      patients over the last one and a half decade.
AB  - AML with FLT3 ITD mutations are associated with poor outcome. We reviewed
      outcomes of patients with FLT3 ITD mutated AML to investigate trends over time.
      We analyzed 224 AML patients (excluding patients with core binding factor and
      acute promyelocytic leukemia) referred to our institution between 2000 and 2014.
      Patients were divided into five cohorts by era: 2000-2002 (Era 1, n = 19), 2003
      2005 (Era 2, n = 41), 2006-2008 (Era 3, n = 53), 2009-2011 (Era 4, n = 55), and
      2012-2014 (Era 5, n = 56) to analyze differences in outcome. The baseline
      characteristics were not statistically different across Eras. The response rate
      (CR/CRp) from Era 1-5 was 68%, 49%, 72%, 73%, and 75%, respectively. The overall
      response rate (all Eras) with chemotherapy alone versus chemotherapy plus FLT3
      inhibitor was 67% and 72.5%, respectively (P = 0.4). The median time to relapse
      was 6, 3.6, 7.9, 8.1 months and not reached from Eras 1 through 5, respectively
      (P = 0.001). The median OS has improved: 9.6, 7.6, 14.4, 15.7, and 17.8 month
      from Eras 1-5, respectively (P = <0.001). Stem cell transplant as a time
      dependent variable, showed better OS in the univariate analysis (HR: 0.57, 95%
      CI: 0.39-0.84, P = 0.004) but did not retained its significance in multivariate
      analysis (HR: 0.75, 95% CI: 0.50-1.13, P = 0.16). Our data suggest improvement in
      outcome of FLT3 ITD mutated AML patients over the last 15 years. This is probably
      due to improvement in treatment strategies, including but not limited to
      integration of FLT3 inhibitors and increased use of SCT.

PMID- 26299959
TI  - Presenilin 1 Maintains Lysosomal Ca(2+) Homeostasis via TRPML1 by Regulating
      vATPase-Mediated Lysosome Acidification.
AB  - Presenilin 1 (PS1) deletion or Alzheimer's disease (AD)-linked mutations disrupt
      lysosomal acidification and proteolysis, which inhibits autophagy. Here, we
      establish that this phenotype stems from impaired glycosylation and instability
      of vATPase V0a1 subunit, causing deficient lysosomal vATPase assembly and
      function. We further demonstrate that elevated lysosomal pH in Presenilin 1
      knockout (PS1KO) cells induces abnormal Ca(2+) efflux from lysosomes mediated by
      TRPML1 and elevates cytosolic Ca(2+). In WT cells, blocking vATPase activity or
      knockdown of either PS1 or the V0a1 subunit of vATPase reproduces all of these
      abnormalities. Normalizing lysosomal pH in PS1KO cells using acidic nanoparticles
      restores normal lysosomal proteolysis, autophagy, and Ca(2+) homeostasis, but
      correcting lysosomal Ca(2+) deficits alone neither re-acidifies lysosomes nor
      reverses proteolytic and autophagic deficits. Our results indicate that vATPase
      deficiency in PS1 loss-of-function states causes lysosomal/autophagy deficits and
      contributes to abnormal cellular Ca(2+) homeostasis, thus linking two AD-related
      pathogenic processes through a common molecular mechanism.

PMID- 26299960
TI  - Functional Gene Correction for Cystic Fibrosis in Lung Epithelial Cells Generated
      from Patient iPSCs.
AB  - Lung disease is a major cause of death in the United States, with current
      therapeutic approaches serving only to manage symptoms. The most common chronic
      and life-threatening genetic disease of the lung is cystic fibrosis (CF) caused
      by mutations in the cystic fibrosis transmembrane regulator (CFTR). We have
      generated induced pluripotent stem cells (iPSCs) from CF patients carrying a
      homozygous deletion of F508 in the CFTR gene, which results in defective
      processing of CFTR to the cell membrane. This mutation was precisely corrected
      using CRISPR to target corrective sequences to the endogenous CFTR genomic locus,
      in combination with a completely excisable selection system, which significantly
      improved the efficiency of this correction. The corrected iPSCs were subsequently
      differentiated to mature airway epithelial cells where recovery of normal CFTR
      expression and function was demonstrated. This isogenic iPSC-based model system
      for CF could be adapted for the development of new therapeutic approaches.

PMID- 26299961
TI  - Adenylylation of Gyrase and Topo IV by FicT Toxins Disrupts Bacterial DNA
      Topology.
AB  - Toxin-antitoxin (TA) modules are ubiquitous molecular switches controlling
      bacterial growth via the release of toxins that inhibit cell proliferation. Most
      of these toxins interfere with protein translation, but a growing variety of
      other mechanisms hints at a diversity that is not yet fully appreciated. Here, we
      characterize a group of FIC domain proteins as toxins of the conserved and
      abundant FicTA family of TA modules, and we reveal that they act by suspending
      control of cellular DNA topology. We show that FicTs are enzymes that adenylylate
      DNA gyrase and topoisomerase IV, the essential bacterial type IIA topoisomerases,
      at their ATP-binding site. This modification inactivates both targets by blocking
      their ATPase activity, and, consequently, causes reversible growth arrest due to
      the knotting, catenation, and relaxation of cellular DNA. Our results give
      insight into the regulation of DNA topology and highlight the remarkable
      plasticity of FIC domain proteins.

PMID- 26299962
TI  - Antagonistic Effects of BACE1 and APH1B-gamma-Secretase Control Axonal Guidance
      by Regulating Growth Cone Collapse.
AB  - BetaACE1 is the major drug target for Alzheimer's disease, but we know
      surprisingly little about its normal function in the CNS. Here, we show that this
      protease is critically involved in semaphorin 3A (Sema3A)-mediated axonal
      guidance processes in thalamic and hippocampal neurons. An active membrane-bound
      proteolytic CHL1 fragment is generated by BACE1 upon Sema3A binding. This
      fragment relays the Sema3A signal via ezrin-radixin-moesin (ERM) proteins to the
      neuronal cytoskeleton. APH1B-gamma-secretase-mediated degradation of this
      fragment stops the Sema3A-induced collapse and sensitizes the growth cone for the
      next axonal guidance cue. Thus, we reveal a cycle of proteolytic activity
      underlying growth cone collapse and restoration used by axons to find their
      correct trajectory in the brain. Our data also suggest that BACE1 and gamma
      secretase inhibition have physiologically opposite effects in this process,
      supporting the idea that combination therapy might attenuate some of the side
      effects associated with these drugs.

PMID- 26299963
TI  - An Allosteric Interaction Links USP7 to Deubiquitination and Chromatin Targeting
      of UHRF1.
AB  - The protein stability and chromatin functions of UHRF1 (ubiquitin-like,
      containing PHD and RING finger domains, 1) are regulated in a cell-cycle
      dependent manner. We report a structural characterization of the complex between
      UHRF1 and the deubiquitinase USP7. The first two UBL domains of USP7 bind to the
      polybasic region (PBR) of UHRF1, and this interaction is required for the USP7
      mediated deubiquitination of UHRF1. Importantly, we find that the USP7-binding
      site of the UHRF1 PBR overlaps with the region engaging in an intramolecular
      interaction with the N-terminal tandem Tudor domain (TTD). We show that the USP7
      UHRF1 interaction perturbs the TTD-PBR interaction of UHRF1, thereby shifting the
      conformation of UHRF1 from a TTD-"occluded" state to a state open for multivalent
      histone binding. Consistently, introduction of a USP7-interaction-defective
      mutation to UHRF1 significantly reduces its chromatin association. Together,
      these results link USP7 interaction to the dynamic deubiquitination and chromatin
      association of UHRF1.

PMID- 26299964
TI  - PGC-1alpha Modulates Telomere Function and DNA Damage in Protecting against Aging
      Related Chronic Diseases.
AB  - Cellular senescence and organismal aging predispose age-related chronic diseases,
      such as neurodegenerative, metabolic, and cardiovascular disorders. These
      diseases emerge coincidently from elevated oxidative/electrophilic stress,
      inflammation, mitochondrial dysfunction, DNA damage, and telomere dysfunction and
      shortening. Mechanistic linkages are incompletely understood. Here, we show that
      ablation of peroxisome proliferator-activated receptor gamma coactivator-1alpha
      (PGC-1alpha) accelerates vascular aging and atherosclerosis, coinciding with
      telomere dysfunction and shortening and DNA damage. PGC-1alpha deletion reduces
      expression and activity of telomerase reverse transcriptase (TERT) and increases
      p53 levels. Ectopic expression of PGC-1alpha coactivates TERT transcription and
      reverses telomere malfunction and DNA damage. Furthermore, alpha lipoic acid
      (ALA), a non-dispensable mitochondrial cofactor, upregulates PGC-1alpha-dependent
      TERT and the cytoprotective Nrf-2-mediated antioxidant/electrophile-responsive
      element (ARE/ERE) signaling cascades, and counteracts high-fat-diet-induced, age
      dependent arteriopathy. These results illustrate the pivotal importance of PGC
      1alpha in ameliorating senescence, aging, and associated chronic diseases, and
      may inform novel therapeutic approaches involving electrophilic specificity.

PMID- 26299966
TI  - The Smc5/6 Complex Is an ATP-Dependent Intermolecular DNA Linker.
AB  - The structural maintenance of chromosome (SMC) protein complexes cohesin and
      condensin and the Smc5/6 complex (Smc5/6) are crucial for chromosome dynamics and
      stability. All contain essential ATPase domains, and cohesin and condensin
      interact with chromosomes through topological entrapment of DNA. However, how
      Smc5/6 binds DNA and chromosomes has remained largely unknown. Here, we show that
      purified Smc5/6 binds DNA through a mechanism that requires ATP hydrolysis by the
      complex and circular DNA to be established. This also promotes topoisomerase 2
      dependent catenation of plasmids, suggesting that Smc5/6 interconnects two DNA
      molecules using ATP-regulated topological entrapment of DNA, similar to cohesin.
      We also show that a complex containing an Smc6 mutant that is defective in ATP
      binding fails to interact with DNA and chromosomes and leads to cell death with
      concomitant accumulation of DNA damage when overexpressed. Taken together, these
      results indicate that Smc5/6 executes its cellular functions through ATP
      regulated intermolecular DNA linking.

PMID- 26299965
TI  - Mitotic Stress Is an Integral Part of the Oncogene-Induced Senescence Program
      that Promotes Multinucleation and Cell Cycle Arrest.
AB  - Oncogene-induced senescence (OIS) is a tumor suppression mechanism that blocks
      cell proliferation in response to oncogenic signaling. OIS is frequently
      accompanied by multinucleation; however, the origin of this is unknown. Here, we
      show that multinucleate OIS cells originate mostly from failed mitosis. Prior to
      senescence, mutant H-RasV12 activation in primary human fibroblasts compromised
      mitosis, concordant with abnormal expression of mitotic genes functionally linked
      to the observed mitotic spindle and chromatin defects. Simultaneously, H-RasV12
      activation enhanced survival of cells with damaged mitoses, culminating in
      extended mitotic arrest and aberrant exit from mitosis via mitotic slippage. ERK
      dependent transcriptional upregulation of Mcl1 was, at least in part, responsible
      for enhanced survival and slippage of cells with mitotic defects. Importantly,
      mitotic slippage and oncogene signaling cooperatively induced senescence and key
      senescence effectors p21 and p16. In summary, activated Ras coordinately triggers
      mitotic disruption and enhanced cell survival to promote formation of
      multinucleate senescent cells.

PMID- 26299967
TI  - Recovery from Age-Related Infertility under Environmental Light-Dark Cycles
      Adjusted to the Intrinsic Circadian Period.
AB  - Female reproductive function changes during aging with the estrous cycle becoming
      more irregular during the transition to menopause. We found that intermittent
      shifts of the light-dark cycle disrupted regularity of estrous cycles in middle
      aged female mice, whose estrous cycles were regular under unperturbed 24-hr light
      dark cycles. Although female mice deficient in Cry1 or Cry2, the core components
      of the molecular circadian clock, exhibited regular estrous cycles during youth,
      they showed accelerated senescence characterized by irregular and unstable
      estrous cycles and resultant infertility in middle age. Notably, tuning the
      period length of the environmental light-dark cycles closely to the endogenous
      one inherent in the Cry-deficient females restored the regularity of the estrous
      cycles and, consequently, improved fertility in middle age. These results suggest
      that reproductive potential can be strongly influenced by age-related changes in
      the circadian system and normal reproductive functioning can be rescued by the
      manipulation of environmental timing signals.

PMID- 26299968
TI  - Astrocyte Depletion Impairs Redox Homeostasis and Triggers Neuronal Loss in the
      Adult CNS.
AB  - Although the importance of reactive astrocytes during CNS pathology is well
      established, the function of astroglia in adult CNS homeostasis is less well
      understood. With the use of conditional, astrocyte-restricted protein synthesis
      termination, we found that selective paralysis of GFAP(+) astrocytes in vivo led
      to rapid neuronal cell loss and severe motor deficits. This occurred while
      structural astroglial support still persisted and in the absence of any major
      microvascular damage. Whereas loss of astrocyte function did lead to microglial
      activation, this had no impact on the neuronal loss and clinical decline.
      Neuronal injury was caused by oxidative stress resulting from the reduced redox
      scavenging capability of dysfunctional astrocytes and could be prevented by the
      in vivo treatment with scavengers of reactive oxygen and nitrogen species
      (ROS/RNS). Our results suggest that the subpopulation of GFAP(+) astrocytes
      maintain neuronal health by controlling redox homeostasis in the adult CNS.

PMID- 26299969
TI  - Lipid Cooperativity as a General Membrane-Recruitment Principle for PH Domains.
AB  - Many cellular processes involve the recruitment of proteins to specific
      membranes, which are decorated with distinctive lipids that act as docking sites.
      The phosphoinositides form signaling hubs, and we examine mechanisms underlying
      recruitment. We applied a physiological, quantitative, liposome microarray-based
      assay to measure the membrane-binding properties of 91 pleckstrin homology (PH)
      domains, the most common phosphoinositide-binding target. 10,514 experiments
      quantified the role of phosphoinositides in membrane recruitment. For most
      domains examined, the observed binding specificity implied cooperativity with
      additional signaling lipids. Analyses of PH domains with similar lipid-binding
      profiles identified a conserved motif, mutations in which-including some found in
      human cancers-induced discrete changes in binding affinities in vitro and protein
      mislocalization in vivo. The data set reveals cooperativity as a key mechanism
      for membrane recruitment and, by enabling the interpretation of disease
      associated mutations, suggests avenues for the design of small molecules
      targeting PH domains.

PMID- 26299970
TI  - Genomic DISC1 Disruption in hiPSCs Alters Wnt Signaling and Neural Cell Fate.
AB  - Genetic and clinical association studies have identified disrupted in
      schizophrenia 1 (DISC1) as a candidate risk gene for major mental illness. DISC1
      is interrupted by a balanced chr(1;11) translocation in a Scottish family in
      which the translocation predisposes to psychiatric disorders. We investigate the
      consequences of DISC1 interruption in human neural cells using TALENs or CRISPR
      Cas9 to target the DISC1 locus. We show that disruption of DISC1 near the site of
      the translocation results in decreased DISC1 protein levels because of nonsense
      mediated decay of long splice variants. This results in an increased level of
      canonical Wnt signaling in neural progenitor cells and altered expression of fate
      markers such as Foxg1 and Tbr2. These gene expression changes are rescued by
      antagonizing Wnt signaling in a critical developmental window, supporting the
      hypothesis that DISC1-dependent suppression of basal Wnt signaling influences the
      distribution of cell types generated during cortical development.

PMID- 26299971
TI  - Disruption of the Rag-Ragulator Complex by c17orf59 Inhibits mTORC1.
AB  - mTORC1 controls key processes that regulate cell growth, including mRNA
      translation, ribosome biogenesis, and autophagy. Environmental amino acids
      activate mTORC1 by promoting its recruitment to the cytosolic surface of the
      lysosome, where its kinase is activated downstream of growth factor signaling.
      mTORC1 is brought to the lysosome by the Rag GTPases, which are tethered to the
      lysosomal membrane by Ragulator, a lysosome-bound scaffold. Here, we identify
      c17orf59 as a Ragulator-interacting protein that regulates mTORC1 activity
      through its interaction with Ragulator at the lysosome. The binding of c17orf59
      to Ragulator prevents Ragulator interaction with the Rag GTPases, both in cells
      and in vitro, and decreases Rag GTPase lysosomal localization. Disruption of the
      Rag-Ragulator interaction by c17orf59 impairs mTORC1 activation by amino acids by
      preventing mTOR from reaching the lysosome. By disrupting the Rag-Ragulator
      interaction to inhibit mTORC1, c17orf59 expression may represent another
      mechanism to modulate nutrient sensing by mTORC1.

PMID- 26299973
TI  - Salmonella Disrupts Host Endocytic Trafficking by SopD2-Mediated Inhibition of
      Rab7.
AB  - Intracellular bacterial pathogens of a diverse nature share the ability to evade
      host immunity by impairing trafficking of endocytic cargo to lysosomes for
      degradation, a process that is poorly understood. Here, we show that the
      Salmonella enterica type 3 secreted effector SopD2 mediates this process by
      binding the host regulatory GTPase Rab7 and inhibiting its nucleotide exchange.
      Consequently, this limits Rab7 interaction with its dynein- and kinesin-binding
      effectors RILP and FYCO1 and thereby disrupts host-driven regulation of
      microtubule motors. Our study identifies a bacterial effector capable of directly
      binding and thereby modulating Rab7 activity and a mechanism of endocytic
      trafficking disruption that may provide insight into the pathogenesis of other
      bacteria. Additionally, we provide a powerful tool for the study of Rab7
      function, and a potential therapeutic target.

PMID- 26299974
TI  - Murine embryonic stem cell line CGR8 expresses all subtypes of muscarinic
      receptors and multiple nicotinic receptor subunits: Down-regulation of alpha4-
      and beta4-subunits during early differentiation.
AB  - Non-neuronal acetylcholine mediates its cellular effects via stimulation of the G
      protein-coupled muscarinic receptors and the ligand-gated ion channel nicotinic
      receptors. The murine embryonic stem cell line CGR8 synthesizes and releases non
      neuronal acetylcholine. In the present study a systematic investigation of the
      expression of nicotinic receptor subunits and muscarinic receptors was performed,
      when the stem cells were grown in the presence or absence of LIF, as the latter
      condition induces early differentiation. CGR8 cells expressed multiple nicotinic
      receptor subtypes (alpha3, alpha4, alpha7, alpha9, alpha10, beta1, beta2, beta3,
      beta4, gamma, delta, epsilon) and muscarinic receptors (M1, M3, M4, M5); M2 was
      detected only in 2 out of 8 cultures. LIF removal caused a down-regulation only
      of the alpha4- and beta4-subunit. In conclusion, more or less the whole
      repertoire of cholinergic receptors is expressed on the murine embryonic stem
      cell line CGR8 for mediating cellular signaling of non-neuronal acetylcholine
      which acts via auto- and paracrine pathways. During early differentiation of the
      murine CGR8 stem cell signaling via nicotinic receptors containing alpha4- or
      beta4 subunits is reduced. Thus, the so-called neuronal alpha4 nicotine receptor
      composed of these subunits may be involved in the regulation of pluripotency in
      this murine stem cell line. 

PMID- 26299972
TI  - PRC2 Is Required to Maintain Expression of the Maternal Gtl2-Rian-Mirg Locus by
      Preventing De Novo DNA Methylation in Mouse Embryonic Stem Cells.
AB  - Polycomb Repressive Complex 2 (PRC2) function and DNA methylation (DNAme) are
      typically correlated with gene repression. Here, we show that PRC2 is required to
      maintain expression of maternal microRNAs (miRNAs) and long non-coding RNAs
      (lncRNAs) from the Gtl2-Rian-Mirg locus, which is essential for full pluripotency
      of iPSCs. In the absence of PRC2, the entire locus becomes transcriptionally
      repressed due to gain of DNAme at the intergenic differentially methylated
      regions (IG-DMRs). Furthermore, we demonstrate that the IG-DMR serves as an
      enhancer of the maternal Gtl2-Rian-Mirg locus. Further analysis reveals that PRC2
      interacts physically with Dnmt3 methyltransferases and reduces recruitment to and
      subsequent DNAme at the IG-DMR, thereby allowing for proper expression of the
      maternal Gtl2-Rian-Mirg locus. Our observations are consistent with a mechanism
      through which PRC2 counteracts the action of Dnmt3 methyltransferases at an
      imprinted locus required for full pluripotency.

PMID- 26299975
TI  - Green tea polyphenols change the profile of inflammatory cytokine release from
      lymphocytes of obese and lean rats and protect against oxidative damage.
AB  - This study aimed to investigate whether green tea polyphenols (GT) modulate some
      functional parameters of lymphocytes from obese rats. Male Wistar rats were
      treated with GT by gavage (12 weeks/5 days/week; 500 mg/kg of body weight) and
      obesity was induced by cafeteria diet (8 weeks). Lymphocytes were obtained from
      mesenteric lymph nodes for analyses. In response to the cafeteria diet we
      observed an increase in activity of the metabolic enzyme hexokinase, ROS
      production, MnSOD, CuZnSOD and GR enzyme activities and proliferation capacity of
      the cells (baseline), whereas IL-10 production was decreased. Obese rats treated
      with GT decreased cell proliferation (under ConA stimulation). Hexokinase and
      G6PDH activity, ROS production and MnSOD, CuZnSOD, GPx and GR enzymes remained
      increased, accompanied by an increase in Nrf2 mRNA level. There was a decrease in
      pro-inflammatory IL-2, IL-6, IL-1beta, TNF-alpha cytokines that were accompanied
      by a decrease in the mRNA level of TRL4 while IL-10 production was increased in
      obese rats treated with GT. GT treatment of lean rats showed similar results to
      that of obese rats treated with GT, indicating that the effects of GT are
      independent of diet. Foxp3 and IRF4 mRNA levels were increased by GT. In
      conclusion, cafeteria diet modulated the function of lymphocytes from lymph
      nodes, increasing ROS production and decreasing anti-inflammatory IL-10, which
      could contribute to the inflammatory state in obesity. GT reduced ROS production,
      improving the redox status and reducing pro-inflammatory cytokine production by
      lymphocytes, suggesting that GT treatment may be driving lymphocytes to a more
      anti-inflammatory than pro-inflammatory microenvironment.

PMID- 26299977
TI  - Metagenomic insights into the effects of volatile fatty acids on microbial
      community structures and functional genes in organotrophic anammox process.
AB  - To explore the metabolic versatility of "Candidatus Brocadia sinica" in the
      presence of VFAs, the impacts of VFAs on anammox activity and nitrogen removal
      were investigated in this study. Results found that low VFAs concentrations has
      no affect on anammox activity and the removal efficiencies of NH4(+)-N and NO2(-)
      N. However, "Ca. Brocadia sinica" showed higher adaptability to some VFAs
      stresses. Furthermore, Illumina MiSeq pyrosequencing results indicated that the
      microbial community structures varied significantly and the phyla Chloroflexi,
      Proteobacteria, Bacteroidetes and Chlorobi were dominated. Finally, qPCR was
      performed to validate the growth of anammox bacteria and gain the quantitative
      insights into the correlation between nitrogen transformation rates and the key
      functional genes in the organotrophic anammox system. Combined analysis clearly
      demonstrated that the coupling of the anammox, denitrification and DNRA were the
      noteworthy pathway for the simultaneous removal of nitrogen and organic carbon.

PMID- 26299976
TI  - Application of human haploid cell genetic screening model in identifying the
      genes required for resistance to environmental toxicants: Chlorpyrifos as a case
      study.
AB  - INTRODUCTION: High-throughput loss-of-function genetic screening tools in yeast
      or other model systems except in mammalian cells have been implemented to study
      human susceptibility to chemical toxicity. Here, we employed a newly developed
      human haploid cell (KBM7)-based mutagenic screening model (KBM7-mu cells) and
      examined its applicability in identifying genes whose absence allows cells to
      survive and proliferate in the presence of chemicals. METHODS: KBM7-mu cells were
      exposed to 200 MUM Chlorpyrifos (CPF), a widely used organophosphate pesticide, a
      dose causing approximately 50% death of cells after 48h of treatment. After a 2-3
      week period of continuous CPF exposure, survived single cell colonies were
      recovered and used for further analysis. DNA isolated from these cells was
      amplified using Splinkerette PCR with specific designed primers, and sequenced to
      determine the genomic locations with virus insertion and identify genes affected
      by the insertion. Quantitative realtime reverse transcription PCR (qRT-PCR) was
      used to confirm the knockdown of transcription of identified target genes.
      RESULTS: We identified total 9 human genes in which the cells carrying these
      genes conferred the resistance to CPF, including AGPAT6, AIG1, ATP8B2, BIK,
      DCAF12, FNBP4, LAT2, MZF1-AS1 and PPTC7. MZF1-AS1 is an antisense RNA and not
      included in the further analysis. qRT-PCR results showed that the expression of 6
      genes was either significantly reduced or completely lost. There were no changes
      in the expression of DCAF12 and AGPAT6 genes between the KBM7-mu and the control
      KBM7 cells. DISCUSSION: The KBM7-mu genetic screening system can be modified and
      applied to identify novel susceptibility genes in response to environmental
      toxicants, which could provide valuable insights into potential mechanisms of
      toxicity.

PMID- 26299978
TI  - High-yield production of biosugars from Gracilaria verrucosa by acid and
      enzymatic hydrolysis processes.
AB  - Gracilaria verrucosa, the red alga, is a suitable feedstock for biosugar
      production. This study analyzes biosugar production by the hydrolysis of G.
      verrucosa conducted under various conditions (i.e., various acid concentrations,
      substrate concentrations, reaction times, and enzyme dosages). The acid
      hydrolysates of G. verrucosa yielded a total of 7.47g/L (37.4%) and 10.63g/L
      (21.26%) of reducing sugars under optimal small (30mL) and large laboratory-scale
      (1L) hydrolysis processes, respectively. Reducing sugar obtained from acid and
      enzymatic hydrolysates were 10% higher, with minimum by-products, than those
      reported in other studies. The mass balance for the small laboratory-scale
      process showed that the acid and enzymatic hydrolysates had a carbohydrate
      conversion of 57.2%. The mass balance approach to the entire hydrolysis process
      of red seaweed for biosugar production can be applied to other saccharification
      processes.

PMID- 26299979
TI  - In situ high-valued utilization and transformation of sugars from Dioscorea
      zingiberensis C.H. Wright for clean production of diosgenin.
AB  - The industrial production of diosgenin in China generates a large amount of high
      sugar wastes with low bioavailability, which causes serious pollution to the
      environment. In this study, a new clean and efficient process for the production
      of diosgenin was developed using sugars through in situ high-valued
      transformation. The sugar mixture from Dioscorea zingiberensis C.H. Wright
      contained abundant beneficial components. Nine typical microorganisms that
      produced intracellular products were evaluated. Saccharopolyspora spinosa was
      selected for recursive protoplast fusion to increase the spinosad yield by 46.3%
      compared with that of the wildtype. Diosgenin and spinosad co-production was
      conducted in a 100L bioreactor, with pH controlled by adding glucose. The
      biological oxygen demand of the effluent water decreased from 15,000mg/L to
      450mg/L; hence, the proposed process is environment friendly.

PMID- 26299980
TI  - Assessing the environmental fate of S-metolachlor, its commercial product
      Mercantor Gold(r) and their photoproducts using a water-sediment test and in
      silico methods.
AB  - Pesticides enter surface and groundwater by several routes in which partition to
      sediment contributes to their fate by abiotic (e.g. photolysis, hydrolysis) and
      biotic processes. Yet, little is known about S-metolachlor (SM) transformation in
      water-sediment systems. Therefore, a newly developed screening water-sediment
      test (WST) was applied to compare biodegradation and sorption processes between
      pure SM and Mercantor Gold(r) (MG), a commercial formulation of SM. Photolysis in
      water was performed by Xe lamp irradiation. Subsequently, the biodegradability of
      SM and MG photolysis mixtures was examined in WST. The primary elimination of SM
      from water phase was monitored and structures of its TPs resulting from
      biotransformation (bio-TPs) were elucidated by LC-MS/MS. SM was extracted from
      sediment in order to estimate the role of sorption in WST for its elimination. A
      set of in silico prediction software tools was applied for toxicity assessment of
      SM and its bio-TPs. Obtained results suggest that the MG adjuvants do not
      significantly affect biodegradation, but do influence diffusion of SM into
      sediment. 50% of SM could not be re-extracted from sediment with 0.01 M CaCl2
      aqueous solution recommended in OECD test guideline for adsorption. Neither the
      parent compound nor the photo-TPs were biodegraded. However, new bio-TPs have
      been generated from SM and MG photo-TPs due to bacterial activity in the water
      sediment interphase. Moreover, according to in silico assessment of the bio-TPs
      the biotransformation might lead to an increased toxicity to the water organisms
      compared with the SM. This might raise concerns of bio-TPs presence in the
      environment.

PMID- 26299981
TI  - Influence of anterior vaginal mesh with concomitant mid-urethral sling surgery on
      stress urinary incontinence: clinical and sonographic outcome.
AB  - INTRODUCTION: To clinically and sonographically evaluate the influence of
      anterior vaginal mesh (AVM) surgery with concomitant mid-urethral sling surgery
      (MUS) for stress urinary incontinence (SUI). MATERIALS AND METHODS: Women with
      severe symptomatic pelvic organ prolapse (POP) stage III or IV with concomitant
      SUI were divided into two groups: Group I had transobturator tape (TOT) and AVM
      surgery and Group II underwent TOT without AVM surgery. Clinical outcome was
      assessed pre-operatively and 1 year post-operatively, while ultrasound
      evaluations were performed after one year. Objective cure was defined as no
      urinary leakage demonstrable on provocative filling cystometry. Subjective SUI
      cure was a negative response to Urogenital Distress Inventory Six (UDI-6)
      (question 3). RESULTS: A total of 97 women were recruited, 57 in Group I and 40
      in Group II. Three women had symptomatic prolapse in Group I and 5 in Group II.
      There were no differences in the ultrasound and clinical outcomes between women
      who had mid-urethral slings with and without AVM. Successful SUI outcome was
      reported in 85 women. Urethral kinking was demonstrable in 50% of successful
      cases, but none with failed outcomes. Subanalysis among those with successful SUI
      outcome (n = 85) and failure (n = 12) revealed the tape, bladder neck and mesh
      mobility was significantly higher (P < 0.001) among those with SUI success.
      CONCLUSIONS: Among women who had MUS, there were no differences in the ultrasound
      and clinical outcome between those who had AVM or otherwise.

PMID- 26299982
TI  - Long-term Mortality in Patients with Asymptomatic Carotid Stenosis: Implications
      for Statin Therapy.
AB  - OBJECTIVE: Recent studies with asymptomatic carotid patients on best medical
      management have shown that the annual risk of stroke has decreased to
      approximately 1%. There is no evidence that a similar decrease in mortality has
      occurred. In addition, the intensity of statin therapy for these patients has not
      yet been determined. The aims of this review were to determine (a) the reported
      long-term all-cause and cardiac-related mortality in patients with asymptomatic
      carotid stenosis (ACS) > 50%, (b) whether there has been a decrease in mortality
      in recent years, (c) the available methods of mortality risk stratification, and
      (d) whether the latest ACC/AHA guidelines on the treatment of serum lipids can be
      applied to this group of patients. METHODS: Systematic review of PubMed,
      EuroPubMed, and Cochrane Library and meta-analysis using random effects for
      pooled proportions were performed regarding long-term all-cause and cardiac
      related mortality and the associated risk factors in ACS patients. The last day
      for literature search was October 30, 2014. RESULTS: Seventeen studies were
      retrieved reporting 5-year all-cause mortality in 11,391 patients with ACS >50%.
      The 5-year cumulative all-cause mortality across all 17 studies was 23.6% (95% CI
      20.50-26.80). Twelve additional studies, reporting both all-cause and cardiac
      mortality with a minimum of 2 year follow-up and involving 4,072 patients were
      identified. Of the 930 deaths reported, 589 (62.9%; 95% CI 58.81-66.89) were
      cardiac-related. This translates into an average cardiac-related mortality of
      2.9% per year. CONCLUSIONS: All-cause and cardiac mortality in ACS patients are
      very high. Although risk stratification is possible, most patients are classified
      as high risk. In view of this high risk, aggressive statin therapy is indicated
      if the new ACC/AHA guidelines on serum lipids are to be adhered to.

PMID- 26299983
TI  - Consequences of Using Self-Protective Behaviors in Nonsexual Assaults: The
      Differential Risk of Completion and Injury by Victim Sex.
AB  - This study examines the consequences of using self-protective behaviors in
      nonsexual assaults. Particular attention is paid to how victim sex modifies
      conclusions regarding the effectiveness of countermeasures as completion or
      injury avoidance strategies. These relationships are tested using 16,309
      incidents of nonsexual assaults from the National Crime Victimization Survey.
      Several outcomes of violent encounters (i.e., completion, injury, injury
      severity) are regressed on measures of self-protective behaviors through a
      sequence of logistic regressions. Interactions between victim sex and self
      protective behavior are also estimated. Forceful physical strategies are
      associated with a greater probability of assault completion and injury.
      Conversely, nonforceful verbal strategies serve as protective factors for both
      completion and injury and nonforceful physical strategies are associated with a
      lower probability of injury. Furthermore, there is some evidence that the
      effectiveness of these countermeasures varies by the sex of the victim. 

PMID- 26299985
TI  - Systemic lupus erythematosus and atherosclerosis: Review of the literature.
AB  - The purpose of this manuscript is to extensively review the literature related to
      systemic lupus erythematosus and atherosclerosis. The conclusion of this review
      has covered accelerated atherosclerosis in systemic lupus erythematosus, the role
      of complement, interferon in premature atherosclerosis, inflammatory mediators
      such as cytokines, leukocytes, innate and adaptive immunity, hydrolytic enzymes,
      reactive oxygen species, vascular endothelial growth factor, toll receptors in
      lupus nephritis, several specific anti-inflammatory pharmacological therapies,
      and potential prevention strategies for atherothrombotic events, interferons and
      the inflammasome. It is important for allergist-immunologists, rheumatologists
      both in academic institutions and in practice to understand this important
      disorder. 

PMID- 26299984
TI  - The critical role of toll-like receptors--From microbial recognition to
      autoimmunity: A comprehensive review.
AB  - Toll-like receptors (TLRs) constitute an important mechanism in the activation of
      innate immune cells including monocytes, macrophages and dendritic cells.
      Macrophage activation by TLRs is pivotal in the initiation of the rapid
      expression of pro-inflammatory cytokines TNF, IL-1beta and IL-6 while promoting
      Th17 responses, all of which play critical roles in autoimmunity. Surprisingly,
      in inflammatory arthritis, activation of specific TLRs can not only induce but
      also inhibit cellular processes associated with bone destruction. The
      intercellular and intracellular orchestration of signals from different TLRs,
      their endogenous or microbial ligands and accessory molecules determine the
      activating or inhibitory responses. Herein, we review the TLR-mediated activation
      of innate immune cells in their activation and differentiation to osteoclasts and
      the capacity of these signals to contribute to bone destruction in arthritis.
      Detailed understanding of the opposing mechanisms of TLRs in the induction and
      suppression of cellular processes in arthritis may pave the way to develop novel
      therapies to treat autoimmunity. 

PMID- 26299986
TI  - Clinical and genetic characterization of the autoinflammatory diseases diagnosed
      in an adult reference center.
AB  - INTRODUCTION: Autoinflammatory diseases (AID) are usually diagnosed during the
      pediatric age. However, adult-onset disease or diagnosis during adulthood has
      been occasionally described. OBJECTIVES: To assess the clinical and genetic
      characteristics of adult patients diagnosed with an AID in an adult referral
      center for AID. METHODS: We retrospectively evaluated clinical and genetic
      features of adult patients (>=16 years) diagnosed with an AID or referred after
      AID diagnosis to the Clinical Unit of AID, at the Department of Autoimmune
      Diseases, Hospital Clinic of Barcelona, from 2008 to 2014. RESULTS: During the
      study period, a genetic study for suspected AID was requested to 90 patients at
      the Department of Autoimmune Diseases. A final diagnosis of monogenic AID was
      achieved in 17 patients (19% of patients tested). Five additional cases were
      diagnosed with periodic fever, aphthous stomatitis, pharyngitis and cervical
      adenitis (PFAPA) syndrome and 10 patients with AID were referred from other adult
      departments. Finally, a total of 32 patients with AID were finally diagnosed or
      monitored in our Clinical Unit. These included 12 (37.5%) familial Mediterranean
      fever, 6 (18.8%) tumour necrosis factor-receptor associated periodic syndrome, 8
      (25%) cryopirin-associated periodic syndromes (Muckle-Wells syndrome [MWS] or
      overlap familial cold-associated periodic syndrome/MWS), 1 (3.1%) mevalonate
      kinase deficiency, and 5 (15.6%) PFAPA. Clinical evidence of disease-onset during
      childhood and adulthood was observed in 15 (47%) and 17 (53%) patients,
      respectively. Overall, the final diagnosis was obtained after a delay of a mean
      of 12 years (range 0-47 years). Compared to children, adult patients with AID in
      our series presented more frequently with non-severe manifestations and none of
      them developed amyloidosis during follow-up. Adult patients also carried higher
      proportion of low-penetrance mutations or polymorphisms and all genetic variants
      were presented in heterozygosis or as heterozygous compounds. CONCLUSIONS: Adult
      disease-onset or delayed diagnosis of AID during adulthood is associated with
      milder disease phenotypes, and seem to be driven by mild genotypes, with
      predominant presence of low-penetrance mutations or polymorphisms.

PMID- 26299988
TI  - Expression of programmed cell death ligand-1 in mastocytosis correlates with
      disease severity.

PMID- 26299987
TI  - Spontaneous atopic dermatitis is mediated by innate immunity, with the secondary
      lung inflammation of the atopic march requiring adaptive immunity.
AB  - BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin condition that can
      occur in early life, predisposing to asthma development in a phenomenon known as
      the atopic march. Although genetic and environmental factors are known to
      contribute to AD and asthma, the mechanisms underlying the atopic march remain
      poorly understood. Filaggrin loss-of-function mutations are a major genetic
      predisposer for the development of AD and progression to AD-associated asthma.
      OBJECTIVE: We sought to experimentally address whether filaggrin mutations in
      mice lead to the development of spontaneous eczematous inflammation and address
      the aberrant immunologic milieu arising in a mouse model of filaggrin deficiency.
      METHODS: Filaggrin mutant mice were generated on the proallergic BALB/c
      background, creating a novel model for the assessment of spontaneous AD-like
      inflammation. Independently recruited AD case collections were analyzed to define
      associations between filaggrin mutations and immunologic phenotypes. RESULTS:
      Filaggrin-deficient mice on a BALB/c background had profound spontaneous AD-like
      inflammation with progression to compromised pulmonary function with age,
      reflecting the atopic march in patients with AD. Strikingly, skin inflammation
      occurs independently of adaptive immunity and is associated with cutaneous
      expansion of IL-5-producing type 2 innate lymphoid cells. Furthermore, subjects
      with filaggrin mutations have an increased frequency of type 2 innate lymphoid
      cells in the skin in comparison with control subjects. CONCLUSION: This study
      provides new insights into our understanding of the atopic march, with innate
      immunity initiating dermatitis and the adaptive immunity required for subsequent
      development of compromised lung function.

PMID- 26299989
TI  - Comment on 'Fluorescence sensing of arsenate at nanomolar level in a greener way:
      naphthalene based probe for living cell imaging'.
AB  - The naphthalene based probe (NAPSAL) described in the entitled communication is
      not stable in water, and therefore NAPSAL is unsuitable as an aqueous arsenate
      sensor.

PMID- 26299990
TI  - Three-dimensional power Doppler with silhouette mode for diagnosis of malignant
      ovarian tumors.

PMID- 26299991
TI  - Complex interventions for preventing diabetic foot ulceration.
AB  - BACKGROUND: Ulceration of the feet, which can lead to the amputation of feet and
      legs, is a major problem for people with diabetes mellitus, and can cause
      substantial economic burden. Single preventive strategies have not been shown to
      reduce the incidence of foot ulceration to a significant extent. Therefore, in
      clinical practice, preventive interventions directed at patients, healthcare
      providers and/or the structure of health care are often combined (complex
      interventions). OBJECTIVES: To assess the effectiveness of complex interventions
      in the prevention of foot ulcers in people with diabetes mellitus compared with
      single interventions, usual care or alternative complex interventions. A complex
      intervention is defined as an integrated care approach, combining two or more
      prevention strategies on at least two different levels of care: the patient, the
      healthcare provider and/or the structure of health care. SEARCH METHODS: For the
      second update we searched the Cochrane Wounds Group Specialised Register
      (searched 22 May 2015), The Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library 2015, Issue 4), The Database of Abstracts of
      Reviews of Effects (DARE) (The Cochrane Library 2015, Issue 4), The Health
      Technology Assessment Database (HTA) (The Cochrane Library 2015, Issue 4), The
      NHS Economic Evaluation Database (NHS EED) (The Cochrane Library 2015, Issue 4),
      Ovid MEDLINE (1946 to 22 May 2015), Ovid MEDLINE (In-Process & Other Non-Indexed
      Citations 21 May, 2015), Ovid EMBASE (1974 to 21 May, 2015) and EBSCO CINAHL
      (1982 to 22 May, 2015). SELECTION CRITERIA: Prospective randomised controlled
      trials (RCTs) which compared the effectiveness of combinations of preventive
      strategies, not solely patient education, for the prevention of foot ulcers in
      people with diabetes mellitus, with single interventions, usual care or
      alternative complex interventions. DATA COLLECTION AND ANALYSIS: Two review
      authors were assigned to independently select studies, to extract study data and
      to assess risk of bias of included studies, using predefined criteria. MAIN
      RESULTS: Only six RCTs met the criteria for inclusion. The study characteristics
      differed substantially in terms of healthcare settings, the nature of the
      interventions studied and outcome measures reported. In three studies that
      compared the effect of an education-centred complex intervention with usual care
      or written instructions, only little evidence of benefit was found. Three studies
      compared the effect of more intensive and comprehensive complex interventions
      with usual care. One study found a significant and cost-effective reduction, one
      of lower extremity amputations (RR 0.30, 95% CI 0.31 to 0.71). One other study
      found a significant reduction of both amputation and foot ulcers. The last study
      reported improvement of patients' self care behaviour. All six included RCTs were
      at high risk of bias, with hardly any of the predefined quality assessment
      criteria met. AUTHORS' CONCLUSIONS: There is no high-quality research evidence
      evaluating complex interventions for preventing diabetic foot ulceration and
      insufficient evidence of benefit.

PMID- 26299992
TI  - Development of LC-MS/MS analysis of cyclic dipeptides and its application to tea
      extract.
AB  - 2,5-Diketopiperazines (DKPs), also called cyclic dipeptides, have been known to
      occur in various foods. Recently, DKPs have attracted attentions as bioactive
      components. There were some reports on analytical methods for DKPs, but the
      number of analyzed DKPs was only a part of all DKPs and the quantitative
      performance was not studied in detail. In this study, we selected 31 kinds of
      DKPs and developed a quantitative and simultaneous analytical method using LC
      MS/MS. This method was applied to DKPs determination in Pu-erh tea, post
      fermentation tea, and 18 kinds of DKPs were determined at concentration of 0.0017
      0.11 ppm. As a result of spiked test, it was concluded that the developed method
      using LC-MS/MS was useful for estimating DKPs concentration in tea.

PMID- 26299993
TI  - Comment on Bristow et al.: Dietary calcium: adverse or beneficial effects of
      supplements?

PMID- 26299994
TI  - State of the art and future directions of pancreatic ductal adenocarcinoma
      therapy.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second cause of
      cancer-related death in 2030. PDAC is the poorest prognostic tumor of the
      digestive tract, with 80% of patients having advanced disease at diagnosis and 5
      year survival rate not exceeding 7%. Until 2010, gemcitabine was the only
      validated therapy for advanced PDAC with a modest improvement in median overall
      survival as compared to best supportive care (5-6 vs 3 months). Multiple phase II
      III studies have used various combinations of gemcitabine with other cytotoxics
      or targeted agents, most in vain, in attempt to improve this outcome. Over the
      past few years, the landscape of PDAC management has undergone major and rapid
      changes with the approval of the FOLFIRINOX and gemcitabine plus nab-paclitaxel
      regimens in patients with metastatic disease. These two active combination
      chemotherapy options yield an improved median overall survival (11.1 vs 8.5
      months, respectively) thus making longer survival a reasonably achievable goal.
      This breakthrough raises some new clinical questions about the management of
      PDAC. Moreover, better knowledge of the environmental and genetic events that
      underpin multistep carcinogenesis and of the microenvironment surrounding cancer
      cells in PDAC has open new perspectives and therapeutic opportunities. In this
      new dynamic context of deep transformation in basic research and clinical
      management aspects of the disease, we gathered updated preclinical and clinical
      data in a multifaceted review encompassing the lessons learned from the past, the
      yet unanswered questions, and the most promising research priorities to be
      addressed for the next 5 years.

PMID- 26299996
TI  - CAEP 2014 Academic Symposium: "How to make research succeed in your department:
      Promoting excellence in Canadian emergency medicine resident research".
AB  - OBJECTIVES: To characterize the current state of Canadian emergency medicine (EM)
      resident research and develop recommendations to promote excellence in this area.
      METHODS: We performed a systematic review of MEDLINE, Embase, and ERIC using
      search terms relevant to EM resident research. We conducted an online survey of
      EM residency program directors from the Royal College of Physicians and Surgeons
      of Canada (RCPSC) and College of Family Physicians of Canada (CFPC). An expert
      panel reviewed these data, presented recommendations at the Canadian Association
      of Emergency Physicians 2014 Academic Symposium, and refined them based on
      feedback received. RESULTS: Of 654 potentially relevant citations, 35 articles
      were included. These were categorized into four themes: 1) expectations and
      requirements, 2) training and assessment, 3) infrastructure and support, and 4)
      dissemination. We received 31 responses from all 31 RCPSC-EM and CFPC-EM
      programs. The majority of EM programs reported requiring a resident scholarly
      project; however, we found wide-ranging expectations for the type of resident
      research performed and how results were disseminated, as well as the degree of
      completion expected. Although 93% of RCPSC-EM programs reported providing formal
      training on how to conduct research, only 53% of CFPC-EM programs reported doing
      so. Almost all programs (94%) reported having infrastructure in place to support
      resident research, but the nature of support was highly variable. Finally, there
      was marked variability regarding the number of resident-published abstracts and
      manuscripts. CONCLUSIONS: Based on the literature, our national survey, and
      discussions with stakeholders, we offer 14 recommendations encompassing goals,
      expectations, training, assessment, infrastructure, and dissemination in order to
      improve Canadian EM resident research.

PMID- 26299997
TI  - Molecular Mechanism of the Affinity Interactions between BAFF and Its Peptides by
      Molecular Simulations.
AB  - B-cell activating factor (BAFF) belonging to the TNF family, plays an important
      role in the proliferation and differentiation of B cells which renders it an
      attractive target for autoimmune diseases. Some peptides have been designed to
      target BAFF for the treatment of autoimmune diseases. Our previous studies
      suggested that peptides TA and DX-814 had competitive bioactivities compared to
      the natural peptide trans-membrane activator and calcium modulator and
      cyclophilin ligand interactor (TACI) in different binding orientations. In this
      study, we carried out molecular modeling and dynamics and molecular docking
      calculations to explore the structural and chemical features responsible for the
      binding affinities of these peptides. Binding free energy calculations,
      mutational analyses were also conducted to validate our findings. The result
      showed that hydrophobic and electrostatic interactions are the dominant forces
      for binding. DX-814 had a similar binding orientation with BCMA in a conserved
      hydrophobic pocket and formed electrostatic interaction with conserved arginine
      residues on the BAFF surface, compared with TA which might interact with a sub
      pocket of BAFF in a different orientation. These results provide a thorough
      understanding of the binding mode between BAFF and its peptide inhibitors at the
      molecular level and further guide inhibitor design. 

PMID- 26299998
TI  - Improvement of Antimicrobial Activity of Pediocin PA-1 by Site-directed
      Mutagenesis in C-terminal Domain.
AB  - Pediocin PA-1 is a well-known Class IIa bacteriocin which shows strong inhibitory
      effect against Listeria monocytogenes. In this work, in order to improve the
      antimicrobial activity, eight single- site mutants and six combination mutants on
      nine interesting sites in the C-terminal region of pediocin PA-1 were constructed
      and expressed in Escherichia coli heterologously. Ten mutants demonstrated
      enhancement activity when performed the agar diffusion test to the indicator
      strain L. monocytogenes. The substitution of glycine in position 29 to alanine
      showed the most distinct increase of antimicrobial activity which clarified that
      29G acted as a significant role as to guide the pediocin PA-1 molecule to dip
      into receptor membrane. Combination mutants of sites 29G to 32A illustrated that
      a hydrophobic tip of the hairpin-like structure and a smaller bundle of the alpha
      helix domain facilitate the penetrating of pediocin PA-1 into a hydrophobic
      domain of the membrane-embedded subunits of the mannose-phosphotransferase system
      (MPTs). 

PMID- 26299999
TI  - Fused hydrophobic elastin-like-peptides (ELP) enhance biological activity of
      tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising
      anticancer agent with tumor-selective apoptotic activity. Formation of aggregates
      as trimer is the prerequisite for TRAIL's function as an apoptosis inducer.
      However the polymerization property of TRAIL has also brought difficulties for
      its production. RGD-TRAIL is an integrin-targeting TRAIL mutant with enhanced
      apoptosisinducing activity towards tumor cells both in vitro and in vivo. When
      expressed in E. coli, TRAIL or its mutant RGDTRAIL usually formed inclusion
      bodies. Their extreme aggregation propensity for aggregation destabilizes the
      protein, leading to poor recovery and therefore low yield from the purification
      process. The low purification efficiency of TRAIL retards its industrial
      application and large-scale production. To avoid the above problems during RGD
      TRAIL production, we employed elastin-like polypeptides (ELPs) for the fusion
      expression of recombinant RGD-TRAIL. Recombinant RGD-TRAIL-ELP was expressed in a
      soluble form and efficiently purified from the clarified cell extracts by three
      rounds of inverse transition cycling (ITC). SDS-PAGE and Western blotting
      analyses of purified RGD-TRAIL-ELP showed that RGD-TRAIL-ELP was successfully
      purified and the yield was up to 10 mg/L of bacterial culture. Apoptosis assay
      was performed in human colorectal carcinoma cells (COLO-205) and human breast
      cancer cell line (MDA-MB-231) to assess the potency of the fusion protein. Fusion
      with hydrophobic ELP effectively enhanced RGD-TRAIL's biological activity. The
      higher activity and appropriate particle size of RGD-TRAIL-ELP could be used for
      RGD-TRAIL delivery in tumor therapy. 

PMID- 26299995
TI  - Cathepsin L targeting in cancer treatment.
AB  - Proteolytic enzymes may serve as promising targets for novel therapeutic
      treatment strategies seeking to impede cancer progression and metastasis. One
      such enzyme is cathepsin L (CTSL), a lysosomal cysteine protease. CTSL
      upregulation, a common occurrence in a variety of human cancers, has been widely
      correlated with metastatic aggressiveness and poor patient prognosis. In
      addition, CTSL has been implicated to contribute to cancer-associated osteolysis,
      a debilitating morbidity affecting both life expectancy and the quality of life.
      In this review, we highlight the mechanisms by which CTSL contributes to tumor
      progression and dissemination and discuss the therapeutic utility of CTSL
      intervention strategies aimed at impeding metastatic progression and bone
      resorption. 

PMID- 26300001
TI  - The putative oncogene CEP72 inhibits the mitotic function of BRCA1 and induces
      chromosomal instability.
AB  - BRCA1 is a tumor-suppressor gene associated with, but not restricted to, breast
      and ovarian cancer and implicated in various biological functions. During
      mitosis, BRCA1 and its positive regulator Chk2 are localized at centrosomes and
      are required for the regulation of microtubule plus end assembly, thereby
      ensuring faithful mitosis and numerical chromosome stability. However, the
      function of BRCA1 during mitosis has not been defined mechanistically. To gain
      insights into the mitotic role of BRCA1 in regulating microtubule assembly, we
      systematically identified proteins interacting with BRCA1 during mitosis and
      found the centrosomal protein Cep72 as a novel BRCA1-interacting protein. CEP72
      is frequently upregulated in colorectal cancer tissues and overexpression of
      CEP72 mirrors the consequences of BRCA1 loss during mitosis. In detail, the
      overexpression of CEP72 causes an increase in microtubule plus end assembly,
      abnormal mitotic spindle formation and the induction of chromosomal instability.
      Moreover, we show that high levels of Cep72 counteract Chk2 as a positive
      regulator of BRCA1 to ensure proper mitotic microtubule assembly. Thus, CEP72
      represents a putative oncogene in colorectal cancer that might negatively
      regulate the mitotic function of BRCA1 to ensure chromosomal stability.

PMID- 26300002
TI  - Intestinal-specific activatable Myb initiates colon tumorigenesis in mice.
AB  - Transcription factor Myb is overexpressed in most colorectal cancers (CRC).
      Patients with CRC expressing the highest Myb are more likely to relapse. We
      previously showed that mono-allelic loss of Myb in an Adenomatous polyposis coli
      (APC)-driven CRC mouse model (Apc(Min/+)) significantly improves survival. Here
      we directly investigated the association of Myb with poor prognosis and how Myb
      co-operates with tumor suppressor genes (TSGs) (Apc) and cell cycle regulator,
      p27. Here we generated the first intestinal-specific, inducible transgenic model;
      a MybER transgene encoding a tamoxifen-inducible fusion protein between Myb and
      the estrogen receptor-alpha ligand-binding domain driven by the intestinal
      specific promoter, Gpa33. This was to mimic human CRC with constitutive Myb
      activity in a highly tractable mouse model. We confirmed that the transgene was
      faithfully expressed and inducible in intestinal stem cells (ISCs) before
      embarking on carcinogenesis studies. Activation of the MybER did not change colon
      homeostasis unless one p27 allele was lost. We then established that MybER
      activation during CRC initiation using a pro-carcinogen treatment, azoxymethane
      (AOM), augmented most measured aspects of ISC gene expression and function and
      accelerated tumorigenesis in mice. CRC-associated symptoms of patients including
      intestinal bleeding and anaemia were faithfully mimicked in AOM-treated MybER
      transgenic mice and implicated hypoxia and vessel leakage identifying an
      additional pathogenic role for Myb. Collectively, the results suggest that Myb
      expands the ISC pool within which CRC is initiated while co-operating with TSG
      loss. Myb further exacerbates CRC pathology partly explaining why high MYB is a
      predictor of worse patient outcome.

PMID- 26300000
TI  - Aberrant RNA splicing in cancer; expression changes and driver mutations of
      splicing factor genes.
AB  - Alternative splicing is a widespread process contributing to structural
      transcript variation and proteome diversity. In cancer, the splicing process is
      commonly disrupted, resulting in both functional and non-functional end-products.
      Cancer-specific splicing events are known to contribute to disease progression;
      however, the dysregulated splicing patterns found on a genome-wide scale have
      until recently been less well-studied. In this review, we provide an overview of
      aberrant RNA splicing and its regulation in cancer. We then focus on the
      executors of the splicing process. Based on a comprehensive catalog of splicing
      factor encoding genes and analyses of available gene expression and somatic
      mutation data, we identify cancer-associated patterns of dysregulation. Splicing
      factor genes are shown to be significantly differentially expressed between
      cancer and corresponding normal samples, and to have reduced inter-individual
      expression variation in cancer. Furthermore, we identify enrichment of predicted
      cancer-critical genes among the splicing factors. In addition to previously
      described oncogenic splicing factor genes, we propose 24 novel cancer-critical
      splicing factors predicted from somatic mutations.

PMID- 26300003
TI  - Dysregulated CRTC1 activity is a novel component of PGE2 signaling that
      contributes to colon cancer growth.
AB  - First identified as a dedicated CREB (cAMP response element-binding protein) co
      activator, CRTC1 (CREB-regulated transcription co-activator 1) has been widely
      implicated in various neuronal functions because of its predominant expression in
      the brain. However, recent evidences converge to indicate that CRTC1 is
      aberrantly activated in an expanding number of adult malignancies. In this study,
      we provide strong evidences of enhanced CRTC1 protein content and transcriptional
      activity in mouse models of sporadic (APC(min/+) mice) or colitis-associated
      colon cancer azoxymethane/dextran sulfate sodium (AOM/DSS-treated mice), and in
      human colorectal tumors specimens compared with adjacent normal mucosa. Among
      signals that could trigger CRTC1 activation during colonic carcinogenesis, we
      demonstrate that treatment with cyclooxygenase 2 (COX2) inhibitors reduced
      nuclear CRTC1 active form levels in colonic tumors of APC(min/+) or AOM/DSS mice.
      In accordance, prostaglandins E2 (PGE2) exposure to human colon cancer cell lines
      promoted CRTC1 dephosphorylation and parallel nuclear translocation, resulting in
      enhanced CRTC1 transcriptional activity, through EP1 and EP2 receptors signaling
      and consecutive calcineurin and protein kinase A activation. In vitro CRTC1 loss
      of function in colon cancer cell lines was associated with reduced viability and
      cell division rate as well as enhanced chemotherapy-induced apoptosis on PGE2
      treatment. Conversely, CRTC1 stable overexpression significantly increased
      colonic xenografts tumor growth, therefore demonstrating the role of CRTC1
      signaling in colon cancer progression. Identification of the transcriptional
      program triggered by enhanced CRTC1 expression during colonic carcinogenesis,
      revealed some notable pro-tumorigenic CRTC1 target genes including NR4A2, COX2,
      amphiregulin (AREG) and IL-6. Finally, we demonstrate that COX2, AREG and IL-6
      promoter activities triggered by CRTC1 are dependent on functional AP1 and CREB
      transcriptional partners. Overall, our study establishes CRTC1 as new mediator of
      PGE2 signaling, unravels the importance of its dysregulation in colon cancer and
      strengthens its use as a bona fide cancer marker.

PMID- 26300005
TI  - Spatiotemporal control of estrogen-responsive transcription in ERalpha-positive
      breast cancer cells.
AB  - Recruitment of transcription machinery to target promoters for aberrant gene
      expression has been well studied, but underlying control directed by distant
      acting enhancers remains unclear in cancer development. Our previous study
      demonstrated that distant estrogen response elements (DEREs) located on
      chromosome 20q13 are frequently amplified and translocated to other chromosomes
      in ERalpha-positive breast cancer cells. In this study, we used three-dimensional
      interphase fluorescence in situ hybridization to decipher spatiotemporal
      gathering of multiple DEREs in the nucleus. Upon estrogen stimulation, scattered
      20q13 DEREs were mobilized to form regulatory depots for synchronized gene
      expression of target loci. A chromosome conformation capture assay coupled with
      chromatin immunoprecipitation further uncovered that ERalpha-bound regulatory
      depots are tethered to heterochromatin protein 1 (HP1) for coordinated chromatin
      movement and histone modifications of target loci, resulting in transcription
      repression. Neutralizing HP1 function dysregulated the formation of DERE-involved
      regulatory depots and transcription inactivation of candidate tumor-suppressor
      genes. Deletion of amplified DEREs using the CRISPR/Cas9 genomic-editing system
      profoundly altered transcriptional profiles of proliferation-associated signaling
      networks, resulting in reduction of cancer cell growth. These findings reveal a
      formerly uncharacterized feature wherein multiple copies of the amplicon
      congregate as transcriptional units in the nucleus for synchronous regulation of
      function-related loci in tumorigenesis. Disruption of their assembly can be a new
      strategy for treating breast cancers and other malignancies.

PMID- 26300006
TI  - ZNF281 contributes to the DNA damage response by controlling the expression of
      XRCC2 and XRCC4.
AB  - ZNF281 is a zinc-finger factor involved in the control of cellular stemness and
      epithelial-mesenchymal transition (EMT). Here, we report that ZNF281 expression
      increased after genotoxic stress caused by DNA-damaging drugs. Comet assays
      demonstrated that DNA repair was delayed in cells silenced for the expression of
      ZNF281 and treated with etoposide. Furthermore, the expression of 10 DNA damage
      response genes was downregulated in cells treated with etoposide and silenced for
      ZNF281. In line with this finding, XRCC2 and XRCC4, two genes that take part in
      homologous recombination and non-homologous end joining, respectively, were
      transcriptionally activated by ZNF281 through a DNA-binding-dependent mechanism,
      as demonstrated by luciferase assays and Chromatin crosslinking
      ImmunoPrecipitation experiments. c-Myc, which also binds to the promoters of
      XRCC2 and XRCC4, was unable to promote their transcription or to modify ZNF281
      activity. Of interest, bioinformatic analysis of 1971 breast cancer patients
      disclosed a significant correlation between the expression of ZNF281 and that of
      XRCC2. In summary, our data highlight, for the first time, the involvement of
      ZNF281 in the cellular response to genotoxic stress through the control exercised
      on the expression of genes that act in different repair mechanisms.

PMID- 26300004
TI  - The TWEAK receptor Fn14 is a potential cell surface portal for targeted delivery
      of glioblastoma therapeutics.
AB  - Fibroblast growth factor-inducible 14 (Fn14; TNFRSF12A) is the cell surface
      receptor for the tumor necrosis factor (TNF) family member TNF-like weak inducer
      of apoptosis (TWEAK). The Fn14 gene is normally expressed at low levels in
      healthy tissues but expression is significantly increased after tissue injury and
      in many solid tumor types, including glioblastoma (GB; formerly referred to as
      'GB multiforme'). GB is the most common and aggressive primary malignant brain
      tumor and the current standard-of-care therapeutic regimen has a relatively small
      impact on patient survival, primarily because glioma cells have an inherent
      propensity to invade into normal brain parenchyma, which invariably leads to
      tumor recurrence and patient death. Despite major, concerted efforts to find new
      treatments, a new GB therapeutic that improves survival has not been introduced
      since 2005. In this review article, we summarize studies indicating that (i) Fn14
      gene expression is low in normal brain tissue but is upregulated in advanced
      brain cancers and, in particular, in GB tumors exhibiting the mesenchymal
      molecular subtype; (ii) Fn14 expression can be detected in glioma cells residing
      in both the tumor core and invasive rim regions, with the maximal levels found in
      the invading glioma cells located within normal brain tissue; and (iii) TWEAK:
      Fn14 engagement as well as Fn14 overexpression can stimulate glioma cell
      migration, invasion and resistance to chemotherapeutic agents in vitro. We also
      discuss two new therapeutic platforms that are currently in development that
      leverage Fn14 overexpression in GB tumors as a way to deliver cytotoxic agents to
      the glioma cells remaining after surgical resection while sparing normal healthy
      brain cells.

PMID- 26300008
TI  - The structure of trimethyltin fluoride.
AB  - The solid-state structure of (CH3)3SnF was reinvestigated by X-ray diffraction
      techniques as well as by multi-nuclear solid-state NMR spectroscopy. Trimethyltin
      fluoride crystallizes from hot ethanol in the orthorhombic space group Pnma at
      room temperature and changes to a low-temperature orthorhombic phase (space
      group: Cmcm) below -70  degrees C. In both modifications, trimethyltin fluoride
      adopts a linear chain structure with symmetric fluorine bridges, in contrast to
      previous reports. During its synthesis, (CH3)3SnF precipitates in another, poorly
      crystalline modification, as shown by powder X-ray diffraction. Solid-state MAS
      NMR experiments of both room-temperature phases of (CH3)3SnF (non-recrystallized
      and recrystallized) were carried out for the (1)H, (13)C, (19)F, and (119)Sn
      nuclei. The (119)Sn{(19)F, (1)H} and (19)F{(1)H} NMR spectra offer unambiguous
      determination for the (19)F and (119)Sn shielding tensors. The (119)Sn{(1)H}
      solid-state NMR spectra are in agreement with pentacoordination of Sn in this
      compound for the non-recrystallized and the recrystallized modifications. Based
      on the solid-state NMR results, the non-recrystallized modification of (CH3)3SnF
      also consists of linear, symmetrically fluorine-bridged chains, and differs from
      the recrystallized orthorhombic phase only in packing of the chains. 

PMID- 26300009
TI  - The genetic and developmental basis of an exaggerated craniofacial trait in East
      African cichlids.
AB  - The evolution of an exaggerated trait can lead to a novel morphology that allows
      organisms to exploit new niches. The molecular bases of such phenotypes can
      reveal insights into the evolution of unique traits. Here, we investigate a rare
      morphological innovation in modern haplochromine cichlids, a flap of fibrous
      tissue that causes a pronounced projection of the snout, which is limited to a
      single genus (Labeotropheus) of Lake Malawi cichlids. We compare flap size in our
      focal species L. fuelleborni (LF) to homologous landmarks in other closely
      related cichlid species that show a range of ecological overlap with LF, and
      demonstrate that variation in flap size is discontinuous among Malawi cichlid
      species. We demonstrate further that flap development in LF begins at early
      juvenile stages, and scales allometrically with body size. We then used an F2
      hybrid mapping population, derived via crossing LF to a close ecological
      competitor that lacks this trait, Tropheops "red cheek" (TRC), to identify
      quantitative trait loci (QTL) that underlie flap development. In all, we
      identified four loci associated with variation in flap size, and for each the LF
      allele contributed to a larger flap. We next cross-referenced our QTL map with
      population genomic data, comparing natural populations of LF and TRC, to identify
      divergent polymorphisms within each QTL interval. Candidate genes for flap
      development are discussed. Together, these data indicate a relatively simple and
      tractable genetic basis for this morphological innovation, which is consistent
      with its apparently sudden and saltatory evolutionary history. J. Exp. Zool.
      (Mol. Dev. Evol.) 324B: 662-670, 2015. (c) 2015 Wiley Periodicals, Inc. 

PMID- 26300007
TI  - NF-kappaB1 p105 suppresses lung tumorigenesis through the Tpl2 kinase but
      independently of its NF-kappaB function.
AB  - Nuclear factor-kappaB (NF-kappaB) is generally believed to be pro-tumorigenic.
      Here we report a tumor-suppressive function for NF-kappaB1, the prototypical
      member of NF-kappaB. While NF-kappaB1 downregulation is associated with high lung
      cancer risk in humans and poor patient survival, NF-kappaB1-deficient mice are
      more vulnerable to lung tumorigenesis induced by the smoke carcinogen, urethane.
      Notably, the tumor-suppressive function of NF-kappaB1 is independent of its
      classical role as an NF-kappaB factor, but instead through stabilization of the
      Tpl2 kinase. NF-kappaB1-deficient tumors exhibit 'normal' NF-kappaB activity, but
      a decreased protein level of Tpl2. Reconstitution of Tpl2 or the NF-kappaB1 p105,
      but not p50 (the processed product of p105), inhibits the tumorigenicity of NF
      kappaB1-deficient lung tumor cells. Remarkably, Tpl2-knockout mice resemble NF
      kappaB1 knockouts in urethane-induced lung tumorigenesis. Mechanistic studies
      indicate that p105/Tpl2 signaling is required for suppressing urethane-induced
      lung damage and inflammation, and activating mutations of the K-Ras oncogene.
      These studies reveal an unexpected, NF-kappaB-independent but Tpl2-depenednt role
      of NF-kappaB1 in lung tumor suppression. These studies also reveal a previously
      unexplored role of p105/Tpl2 signaling in lung homeostasis.

PMID- 26300011
TI  - The effects of intensity on VO2 kinetics during incremental free swimming.
AB  - Swimming and training are carried out with wide variability in distances and
      intensities. However, oxygen uptake kinetics for the intensities seen in swimming
      has not been reported. The purpose of this study was to assess and compare the
      oxygen uptake kinetics throughout low-moderate to severe intensities during
      incremental swimming exercise. We hypothesized that the oxygen uptake kinetic
      parameters would be affected by swimming intensity. Twenty male trained swimmers
      completed an incremental protocol of seven 200-m crawl swims to exhaustion (0.05
      m.s(-1) increments and 30-s intervals). Oxygen uptake was continuously measured
      by a portable gas analyzer connected to a respiratory snorkel and valve system.
      Oxygen uptake kinetics was assessed using a double exponential regression model
      that yielded both fast and slow components of the response of oxygen uptake to
      exercise. From low-moderate to severe swimming intensities changes occurred for
      the first and second oxygen uptake amplitudes (P <= 0.04), time constants (P =
      0.01), and time delays (P <= 0.02). At the heavy and severe intensities, a
      notable oxygen uptake slow component (>255 mL.min(-1)) occurred in all swimmers.
      Oxygen uptake kinetics whilst swimming at different intensities offers relevant
      information regarding cardiorespiratory and metabolic stress that might be useful
      for appropriate performance diagnosis and training prescription. 

PMID- 26300010
TI  - Designing Real-time Decision Support for Trauma Resuscitations.
AB  - BACKGROUND: Use of electronic clinical decision support (eCDS) has been
      recommended to improve implementation of clinical decision rules. Many eCDS
      tools, however, are designed and implemented without taking into account the
      context in which clinical work is performed. Implementation of the pediatric
      traumatic brain injury (TBI) clinical decision rule at one Level I pediatric
      emergency department includes an electronic questionnaire triggered when ordering
      a head computed tomography using computerized physician order entry (CPOE).
      Providers use this CPOE tool in less than 20% of trauma resuscitation cases. A
      human factors engineering approach could identify the implementation barriers
      that are limiting the use of this tool. OBJECTIVES: The objective was to design a
      pediatric TBI eCDS tool for trauma resuscitation using a human factors approach.
      The hypothesis was that clinical experts will rate a usability-enhanced eCDS tool
      better than the existing CPOE tool for user interface design and suitability for
      clinical use. METHODS: This mixed-methods study followed usability evaluation
      principles. Pediatric emergency physicians were surveyed to identify barriers to
      using the existing eCDS tool. Using standard trauma resuscitation protocols, a
      hierarchical task analysis of pediatric TBI evaluation was developed. Five
      clinical experts, all board-certified pediatric emergency medicine faculty
      members, then iteratively modified the hierarchical task analysis until reaching
      consensus. The software team developed a prototype eCDS display using the
      hierarchical task analysis. Three human factors engineers provided feedback on
      the prototype through a heuristic evaluation, and the software team refined the
      eCDS tool using a rapid prototyping process. The eCDS tool then underwent
      iterative usability evaluations by the five clinical experts using video review
      of 50 trauma resuscitation cases. A final eCDS tool was created based on their
      feedback, with content analysis of the evaluations performed to ensure all
      concerns were identified and addressed. RESULTS: Among 26 EPs (76% response
      rate), the main barriers to using the existing tool were that the information
      displayed is redundant and does not fit clinical workflow. After the prototype
      eCDS tool was developed based on the trauma resuscitation hierarchical task
      analysis, the human factors engineers rated it to be better than the CPOE tool
      for nine of 10 standard user interface design heuristics on a three-point scale.
      The eCDS tool was also rated better for clinical use on the same scale, in 84% of
      50 expert-video pairs, and was rated equivalent in the remainder. Clinical
      experts also rated barriers to use of the eCDS tool as being low. CONCLUSIONS: An
      eCDS tool for diagnostic imaging designed using human factors engineering methods
      has improved perceived usability among pediatric emergency physicians.

PMID- 26300012
TI  - Salivary SIgA responses to acute moderate-vigorous exercise in monophasic oral
      contraceptive users.
AB  - The purpose of this study was to examine the effect of oral contraceptive (OC)
      use on salivary secretory immunoglobulin A (SIgA) levels at rest and in response
      to an acute bout of moderate-vigorous exercise during 2 phases of the 4-week OC
      cycle corresponding to different phases of the synthetic menstrual cycle. Ten
      healthy active females completed a cycling at 70% peak oxygen uptake for 45 min
      at 2 time points of an OC cycle: during the equivalent in time to the mid
      follicular phase (day 8 +/- 2) and the mid-luteal phase (day 20 +/- 2). Timed
      unstimulated saliva samples were obtained before, immediately postexercise, and 1
      h postexercise and analyzed for salivary SIgA. Salivary SIgA secretion rate was
      26% (95% confidence limits (CI) 6-46) lower at postexercise compared with pre
      exercise during the synthetic follicular phase (p = 0.019) but no differences
      were observed during the synthetic luteal trial. Saliva flow rate was 11% (95%
      CI, 8-30) lower at postexercise compared with pre-exercise (main effect for time;
      p = 0.025). In conclusion, the pattern of salivary SIgA secretion rate response
      to moderate-vigorous exercise varies across the early and late phases of a
      monophasic OC cycle, with a transient reduction in salivary SIgA responses during
      the synthetic follicular phase. These findings indicate that monophasic OC use
      should be considered when assessing mucosal immune responses to acute exercise. 

PMID- 26300013
TI  - Elbow flexor fatigue modulates central excitability of the knee extensors.
AB  - The present study investigated the effects of exercise-induced elbow flexor
      fatigue on voluntary force output, electromyographic (EMG) activity and
      motoneurone excitability of the nonexercised knee extensor muscles. Eleven
      participants attended 3 testing sessions: (i) control, (ii) unilateral fatiguing
      elbow flexion and (iii) bilateral fatiguing elbow flexion (BiFlex). The
      nonfatigued knee extensor muscles were assessed with thoracic motor evoked
      potentials (TMEPs), maximal compound muscle action potential (Mmax), knee
      extensor maximal voluntary contractions (MVCs), and normalized EMG activity
      before and at 30 s, 3 min, and 5 min postexercise. BiFlex showed significantly
      lower (Delta = -18%, p = 0.03) vastus lateralis (VL) normalized EMG activity
      compared with the control session whereas knee extension MVC force did not show
      any statistical difference between the 3 conditions (p = 0.12). The TMEP.Mmax(-1)
      ratio measured at the VL showed a significantly higher value (Delta = +46%, p =
      0.003) following BiFlex compared with the control condition at 30 s postexercise.
      The results suggest that the lower VL normalized EMG following BiFlex might have
      been due to a reduction in supraspinal motor output because spinal motoneuronal
      responses demonstrated substantially higher value (30 s postexercise) and
      peripheral excitability (compound muscle action potential) showed no change
      following BiFelex than control condition. 

PMID- 26300014
TI  - Development, reliability, and validity testing of Toddler NutriSTEP: a nutrition
      risk screening questionnaire for children 18-35 months of age.
AB  - Nutrition is vital for optimal growth and development of young children.
      Nutrition risk screening can facilitate early intervention when followed by
      nutritional assessment and treatment. NutriSTEP (Nutrition Screening Tool for
      Every Preschooler) is a valid and reliable nutrition risk screening questionnaire
      for preschoolers (aged 3-5 years). A need was identified for a similar
      questionnaire for toddlers (aged 18-35 months). The purpose was to develop a
      reliable and valid Toddler NutriSTEP. Toddler NutriSTEP was developed in 4
      phases. Content and face validity were determined with a literature review,
      parent focus groups (n = 6; 48 participants), and experts (n = 13) (phase A). A
      draft questionnaire was refined with key intercept interviews of 107
      parents/caregivers (phase B). Test-retest reliability (phase C), based on intra
      class correlations (ICC), Kappa (kappa) statistics, and Wilcoxon tests was
      assessed with 133 parents/caregivers. Criterion validity (phase D) was assessed
      using Receiver Operating Characteristic (ROC) curves by comparing scores on the
      Toddler NutriSTEP to a comprehensive nutritional assessment of 200 toddlers with
      a registered dietitian (RD). The Toddler NutriSTEP was reliable between 2
      administrations (ICC = 0.951, F = 20.53, p < 0.001); most questions had moderate
      (kappa >= 0.6) or excellent (kappa >= 0.8) agreement. Scores on the RD nutrition
      risk rating and the Toddler NutriSTEP were correlated (r = 0.67, p < 0.000). The
      area under the ROC curve for moderate and high RD risk ratings were 84.6% and
      82.7%, respectively. Cut-points of >=21 (sensitivity 86%; specificity 61%)
      (moderate risk) and >=26 (sensitivity 95%; specificity 63%) (high risk) were
      determined. The Toddler NutriSTEP questionnaire is both reliable and valid for
      screening for nutritional risk in toddlers. 

PMID- 26300015
TI  - Optimization of surgical outcomes with prehabilitation.
AB  - The concept of preparing surgical candidates with various modalities designed to
      increase physical, physiological, metabolic, and psychosocial reserves is known
      as prehabilitation. Prehabilitation has garnered significant attention in recent
      years as evidence grows describing benefits to clinical and quality of life
      outcomes. Recent research examining hospital length of stay and readmission rates
      provides promising findings with respect to the value of prehabilitation in
      economic and sustainable healthcare models. The role of prehabilitation across
      the surgical experience exploits common surgical wait-times and the teachable
      moment that many patients experience upon the identification of a surgical
      requirement to improve the pre-, peri-, and postoperative experience.
      Prehabilitation incorporates numerous systemic and regional approaches to
      conditioning the surgical candidate. These include exercise, nutrition,
      education, and/or psychosocial approaches that are intended to improve
      preoperative fitness and preparedness. Importantly, this also promotes and
      facilitates health behaviour changes not only preoperatively but during the
      postoperative period and over the long-term. In this paper, we briefly review the
      historical and current perspectives on prehabilitation and comment on
      opportunities for greater clinical and empirical understanding in this field. 

PMID- 26300016
TI  - Sodium bicarbonate supplementation improved MAOD but is not correlated with 200-
      and 400-m running performances: a double-blind, crossover, and placebo-controlled
      study.
AB  - The aim of the study was to investigate the effects of acute supplementation of
      sodium bicarbonate (NaHCO3) on maximal accumulated oxygen deficit (MAOD)
      determined by a single supramaximal effort (MAODALT) in running and the
      correlation with 200- and 400-m running performances. Fifteen healthy men (age,
      23 +/- 4 years; maximal oxygen uptake, 50.6 +/- 6.1 mL.kg(-1).min(-1)) underwent
      a maximal incremental exercise test and 2 supramaximal efforts at 110% of the
      intensity associated with maximal oxygen uptake, which was carried out after
      ingesting either 0.3 g.kg(-1) body weight NaHCO3 or a placebo (dextrose) and
      completing 200- and 400-m performance tests. The study design was double-blind,
      crossover, and placebo-controlled. Significant differences were found between the
      NaHCO3 and placebo conditions for MAODALT (p = 0.01) and the qualitative
      inference for substantial changes showed a very likely positive effect (98%). The
      lactic anaerobic contribution in the NaHCO3 ingestion condition was significantly
      higher (p < 0.01) and showed a very likely positive effect (99% chance), similar
      to that verified for peak blood lactate concentration (p < 0.01). No difference
      was found for time until exhaustion (p = 0.19) or alactic anaerobic contribution
      (p = 0.81). No significant correlations were observed between MAODALT and 200-
      and 400-m running performance tests. Therefore, we can conclude that both MAODALT
      and the anaerobic lactic metabolism are modified after acute NaHCO3 ingestion,
      but it is not correlated with running performance. 

PMID- 26300017
TI  - Effect of moderate exercise on peritoneal neutrophils from juvenile rats.
AB  - Previous studies showed that moderate exercise in adult rats enhances neutrophil
      function, although no studies were performed in juvenile rats. We evaluated the
      effects of moderate exercise on the neutrophil function in juvenile rats.
      Viability and neutrophils function were evaluated. Moderate exercise did not
      impair the viability and mitochondrial transmembrane potential of neutrophils,
      whereas there was greater reactive oxygen species production (164%; p < 0.001)
      and phagocytic capacity (29%; p < 0.05). Our results suggest that moderate
      exercise in juvenile rats improves neutrophil function, similar to adults. 

PMID- 26300018
TI  - Risk Factors for Hyperglycemia During Chemotherapy for Acute Lymphoblastic
      Leukemia Among Taiwanese Children.
AB  - BACKGROUND: Hyperglycemia is common during treatment for pediatric acute
      lymphoblastic leukemia (ALL). Several risk factors have been proposed, but
      emergence of new evidence suggests conflicting results. In view of ethnic
      differences in the propensity for diabetes, this study aims to delineate the
      characteristics of pediatric patients at risk for hyperglycemia during
      chemotherapy in Taiwan. METHODS: This retrospective study involved chart review
      of consecutive patients younger than 18 years with diagnosis of ALL in a medical
      center in Taiwan from 1997 to 2008. Hyperglycemia was defined by random plasma
      glucose levels >=200 mg/dL or fasting glucose levels >=126 mg/dL in at least two
      separate samplings. Risk factors for hyperglycemia were described with crude and
      adjusted odds ratios (OR) with 95% confidence intervals (CI) in the univariate
      and multivariate regression analysis. RESULTS: A total of 133 patients were
      included for analysis. Overall, 22 patients (16.5%) experienced hyperglycemia
      during ALL treatment. Most hyperglycemic episodes occurred within the first 8
      days after prednisolone use. Age older than 10 years was the most important
      predictor of hyperglycemia (adjusted OR = 10.88, 95% CI 2.40-49.37). Patients
      with fasting glucose concentration >=100 mg/dL were also 5.7-fold (95% CI 1.63
      19.93) more likely to develop hyperglycemia, whereas the predictive significance
      of obesity was attenuated after adjustment. CONCLUSION: Assessment of glucose
      concentration should be vigilant in the 1(st) week after prednisolone use during
      ALL treatment. Clinicians should be alert to the patient at risk of
      hyperglycemia, particularly obese adolescents with disarranged glucose
      homeostasis.

PMID- 26300019
TI  - IL-17 polymorphisms and asthma risk: a meta-analysis of 11 single nucleotide
      polymorphisms.
AB  - OBJECTIVE: There has been significant interest in the association between asthma
      and the polymorphisms of IL-17A and IL-17F for a period of time. This work aims
      to present a clearer relationship between asthma and the polymorphisms of IL-17A
      and IL-17F. METHOD: Searches were performed in Medline, EMBASE, and the Chinese
      National Knowledge Infrastructure (CNKI) databases. Pooled odds ratios (ORs) and
      95% confidence intervals (CIs) were calculated to assess the relationship between
      polymorphisms of IL-17A and IL-17F and asthma. RESULTS: Nine studies comprising
      3650 asthmatics and 3370 controls were included in this meta-analysis for all
      single nucleotide polymorphisms (SNPs) (2-6 per SNP). Our study examined the
      polymorphisms of IL-17F rs1889570 (C/T) (CC versus TT: OR = 0.55, 95%CI = 0.41
      0.75; CT versus TT: OR = 0.54, 95%CI = 0.40-0.72; CC/CT versus TT: OR = 0.55,
      95%CI = 0.42-0.72; CC versus CT/TT, OR = 1.83, 95%CI = 1.39-2.41), IL-17A
      rs4711998(A/G) (AA/AG versus GG: OR = 0.67, 95%CI = 0.46-0.98), and IL-17A
      rs3819024(A/G) (AA versus GG: OR = 1.77, 95%CI = 1.39-2.25) and found they were
      significantly related to the risk of asthma. CONCLUSION: Our systematic review
      showed that IL-17F rs1889570(C/T), IL-17A rs4711998(A/G) and IL-17A
      rs3819024(A/G) may be potential risk factors for asthma susceptibility.

PMID- 26300020
TI  - Robotic single-site myomectomy: a step-by-step tutorial.
AB  - OBJECTIVE: To provide a step-by-step description of our published technique of
      single-site robot-assisted laparoscopic myomectomy with the goal of promoting its
      safe adoption. DESIGN: Surgical video tutorial. SETTING: University medical
      center. PATIENT(S): Ten women undergoing single-site robot-assisted laparoscopic
      myomectomy between November 2014 and March 2015. INTERVENTION(S): A 2.5-cm
      vertical incision is made within the umbilicus, through which a multilumen single
      site port (da Vinci Single-Site; Intuitive Surgical) is seated. An 8.5-mm 0
      degree laparoscope is introduced, and the teleoperator (da Vinci Si Surgical
      Platform; Intuitive Surgical) is docked, allowing subsequent placement of two
      curved 5-mm instrument cannulae. Two wristed, semirigid needle drivers are loaded
      onto robotic arms 1 and 2. An 8-mm assistant cannula is also placed through the
      multilumen single-site port; a flexible 2-mm CO2 laser fiber and all conventional
      5-mm laparoscopic instruments are introduced through this cannula as needed.
      Intramyometrial dilute vasopressin is injected, and fibroid enucleation is
      performed. The hysterotomy is repaired in layers with unidirectional barbed
      suture (Stratafix; Ethicon). The teleoperator is undocked. The single-site port
      is exchanged for a self-retaining wound retractor with gel-sealed cap. An
      endoscopic pouch is placed in the abdomen, and the specimen is placed within the
      pouch. The edges of the pouch are exteriorized. Extracorporeal tissue extraction
      is performed with a scalpel. A running mass closure of the fascia and peritoneum
      is performed, followed by a subcuticular closure of the skin. MAIN OUTCOME
      MEASURE(S): Median number and size of fibroids removed, specimen weight,
      operative time, estimated blood loss, and perioperative complications. RESULT(S):
      The technique described in our video was successfully employed in our first 10
      patients. The median number of fibroids removed was 2.5 (range: 1-8); the median
      size of the largest myoma was 6 cm (range: 4-8 cm); the median specimen weight
      was 70 g (range: 26-154 g); the median operating time was 202 minutes (range: 141
      254 minutes); the median blood loss was 87.5 mL (range: 10-300 mL). No
      conversions to multiport robotic or open myomectomy occurred. No major
      complications occurred, and no patients required blood transfusion.
      CONCLUSION(S): Robot-assisted laparoscopic single-site myomectomy employing a
      multilumen port and wristed, semirigid needle drivers is a safe and reproducible
      technique. Our technique allows surgeons to offer myomectomy and contained,
      extracorporeal tissue extraction via a single 2.5-cm umbilical incision in select
      patients with low tumor burden.

PMID- 26300021
TI  - An alternative synthesis of the breast cancer drug fulvestrant (Faslodex(r)):
      catalyst control over C-C bond formation.
AB  - Fulvestrant (Faslodex(r)) was synthesized in four steps (35% overall yield) from
      6-dehydronandrolone acetate. Catalyst controlled, room temperature,
      diastereoselective 1,6-addition of the zirconocene derived from commercially
      available 9-bromonon-1-ene was used in the key C-C bond forming step. 

PMID- 26300022
TI  - The Association Between Depressive Symptoms and Age in Cancer Patients: A
      Multicenter Cross-Sectional Study.
AB  - CONTEXT: There is controversy around the association between depressive symptoms
      and age in adult cancer patients. OBJECTIVES: The aim of this study was to
      evaluate the following hypotheses: 1) cancer patients' depressive symptoms
      decrease with age, and 2) in individuals aged 65 years or older, depressive
      symptoms increase because of the effect of somatic symptoms. METHODS: We
      retrospectively analyzed a database of 356 cancer patients who were consecutively
      recruited in a previous multicenter cross-sectional study. Depressive symptoms
      were assessed by the Patient Health Questionnaire-9 (PHQ-9), and correlations
      with age and other factors were assessed by hierarchical multivariate regression
      analysis. Age was entered as the dependent variable in the first step, patient
      characteristics and cancer-related variables were entered in the second step, and
      somatic symptoms were entered in the last step. We analyzed this model for both
      the total sample and the subpopulation aged 65 years or older. RESULTS: In the
      total sample, the PHQ-9 score was significantly associated with lower age,
      fatigue, and shortness of breath (adjusted R(2) 14.2%). In the subpopulation aged
      65 years or older, no factor was associated with the PHQ-9 score (adjusted R(2)
      7.3%). CONCLUSION: The finding that depressive symptoms in cancer patients
      decreased with age was concordant with our first hypothesis, but the second
      hypothesis was not supported. Younger cancer patients were vulnerable to
      depressive symptoms and should be monitored carefully. Further studies using more
      representative samples are needed to examine in detail the association between
      depressive symptoms and age in older cancer patients.

PMID- 26300024
TI  - To Feed or Not to Feed? A Case Report and Ethical Analysis of Withholding Food
      and Drink in a Patient With Advanced Dementia.
AB  - It is well established that competent patients have the right to refuse
      artificial nutrition and hydration. There is less clarity regarding withholding
      nutrition in patients who lack decision-making capacity but who are still
      physically able to eat and drink. This case highlights the ethical dilemma of
      withholding food and drink in a patient with advanced dementia.

PMID- 26300023
TI  - Symptom Interference Severity and Health-Related Quality of Life in Pulmonary
      Arterial Hypertension.
AB  - CONTEXT: While assessing symptom severity is an important component of evaluating
      symptoms, understanding those symptoms that interfere with patients' lives is
      also key. Pulmonary arterial hypertension (PAH) is a chronic disease resulting in
      right heart failure and increased mortality. Patients with PAH experience
      multiple symptoms but we do not know which symptoms and to what extent their
      symptoms interfere with daily life. OBJECTIVES: To: (1) describe the prevalence
      of those symptoms that interfere with life; (2) describe the severity of symptom
      interference; and (3) determine those sociodemographic and clinical
      characteristics and interfering symptoms associated with health-related quality
      of life (HRQOL) in patients with PAH. METHODS: A convenience sample of 191
      patients with PAH completed a sociodemographic form, the Pulmonary Arterial
      Hypertension Symptom Interference Scale (PAHSIS) and the Medical Outcomes Survey
      Short Form-36 to measure HRQOL. Hierarchical multiple linear regression was used
      to analyze demographic and medical characteristics along with symptom
      interference from the PAHSIS as predictors of HRQOL from the composite mental and
      physical health summary scores of the Short Form-36. RESULTS: The most
      interfering symptoms reported were fatigue, shortness of breath with exertion,
      and difficulty sleeping. Age, gender, functional class, oxygen use, fatigue,
      dizziness, and Raynaud phenomenon were associated with the HRQOL physical health
      summary scores. The symptoms fatigue and SOB while lying down were associated
      with the HRQOL mental health summary scores. CONCLUSION: Patients with PAH are
      experiencing multiple symptoms that are interfering with their HRQOL and ability
      to function.

PMID- 26300025
TI  - Symptom Clusters in Advanced Cancer Patients: An Empirical Comparison of
      Statistical Methods and the Impact on Quality of Life.
AB  - CONTEXT: Symptom clusters in advanced cancer can influence patient outcomes.
      There is large heterogeneity in the methods used to identify symptom clusters.
      OBJECTIVES: To investigate the consistency of symptom cluster composition in
      advanced cancer patients using different statistical methodologies for all
      patients across five primary cancer sites, and to examine which clusters predict
      functional status, a global assessment of health and global quality of life.
      METHODS: Principal component analysis and exploratory factor analysis (with
      different rotation and factor selection methods) and hierarchical cluster
      analysis (with different linkage and similarity measures) were used on a data set
      of 1562 advanced cancer patients who completed the European Organization for the
      Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. RESULTS:
      Four clusters consistently formed for many of the methods and cancer sites: tense
      worry-irritable-depressed (emotional cluster), fatigue-pain, nausea-vomiting, and
      concentration-memory (cognitive cluster). The emotional cluster was a stronger
      predictor of overall quality of life than the other clusters. Fatigue-pain was a
      stronger predictor of overall health than the other clusters. The cognitive
      cluster and fatigue-pain predicted physical functioning, role functioning, and
      social functioning. CONCLUSIONS: The four identified symptom clusters were
      consistent across statistical methods and cancer types, although there were some
      noteworthy differences. Statistical derivation of symptom clusters is in need of
      greater methodological guidance. A psychosocial pathway in the management of
      symptom clusters may improve quality of life. Biological mechanisms underpinning
      symptom clusters need to be delineated by future research. A framework for
      evidence-based screening, assessment, treatment, and follow-up of symptom
      clusters in advanced cancer is essential.

PMID- 26300026
TI  - Understanding What Influences the Health-Related Quality of Life of Hemodialysis
      Patients: A Collaborative Study in England and Ireland.
AB  - CONTEXT: The international cohort of hemodialysis patients is aging and
      increasing in number. Nephrologists have a therapeutic relationship with their
      patients that may span decades. Often overlooked components of chronic disease
      management include symptom control and assessment of health-related quality of
      life (HRQoL). OBJECTIVES: This study describes the symptom profile of a large
      cohort of patients with end-stage renal disease on hemodialysis in England and
      Ireland and evaluates how symptom burden and other factors influence quality-of
      life scores. METHODS: A prospective cross-sectional observational study of
      hemodialysis patients was conducted in Ireland and England during 2011 and 2012.
      Two validated clinical tools were used to determine HRQoL and symptom burden.
      Demographic and clinical data were examined, and regression analysis was used to
      determine associations with HRQoL scores. RESULTS: A total of 893 patients on
      hemodialysis (mean [SD] age 64 [16] years) had a high symptom burden and poor
      HRQoL compared with population norms. Specifically, 64% of patients reported pain
      (95% confidence interval 61%-67%) and 79% reported weakness (95% confidence
      interval 75%-81%). A total of 43 percent of patients reported between six and 10
      symptoms in the week preceding the survey. HRQoL was significantly and
      independently associated with poor mobility and pain and remained significant
      after adjusting for variations in clinical characteristics. Being listed on a
      transplant wait-list register was positively associated with HRQoL. CONCLUSION:
      These findings illustrate the high symptom burden and poor HRQoL of the
      hemodialysis population. Emphasis during clinical reviews on pain assessment and
      on assessing mobility plus interventions, such as pain management and
      physiotherapy/occupational therapy, are practical ways for renal teams to help
      improve patients' quality of life.

PMID- 26300027
TI  - Endocrine abnormalities in HIV-infected women are associated with peak viral load
      - the Children and Women: AntiRetrovirals and Markers of Aging (CARMA) Cohort.
AB  - OBJECTIVES: To investigate the prevalence of endocrine disturbances in a group of
      HIV-positive (HIV+) women and to identify factors affecting presence of these
      disorders. To examine specifically whether cellular ageing, as measured by
      leukocyte telomere length (LTL), is correlated with the presence of endocrine
      disturbance. DESIGN: A cross-sectional retrospective substudy of an ongoing
      prospective cohort study. PATIENTS: Adult HIV+ (>=19 years) women enrolled in the
      CARMA (Children and Women: AntiRetrovirals and Markers of Aging) cohort study (N
      = 192). Prevalences of T2DM, glucose intolerance, dyslipidaemia, thyroid
      disorders, adrenal insufficiency, hypogonadism, primary ovarian insufficiency
      (POI), demographics, HIV and hepatitis C virus (HCV) infection status, baseline
      LTL, combined antiRetroviral therapy (cART) and substance exposures were
      collected. Statistical analysis included univariable followed by multivariable
      Poisson regression and step-wise reduction to refine the multivariable model.
      RESULTS: Prevalence of any endocrine abnormality was 58% (dyslipidaemia 43%,
      glucose intolerance/T2DM 13%, thyroid disorders 15%). In multivariable analysis,
      age was associated with number and type (any, glucose, lipid) of abnormality,
      while increasing body mass index (BMI) was associated with number of diagnoses
      and with glucose metabolism disorders. Interestingly, peak HIV pVL >=100 000
      copies/ml was associated with any abnormality, total number of disorders and
      presence of a thyroid disorder, while any disorder, glucose abnormalities and
      dyslipidaemia were negatively associated with alcohol use. LTL was not associated
      with number or type of endocrine abnormalities in this study. CONCLUSION: Further
      studies examining the relationship between duration and extent of exposure to HIV
      viraemia in relation to developing abnormal endocrine function are warranted.

PMID- 26300028
TI  - Schizophrenia Research: A Progress Report.
AB  - This overview highlights the current hot topics in schizophrenia research. One
      major drawback to progress is the ability to define and focus on the right
      patient group. Schizophrenia is a biased and heterogeneous (group of)
      condition(s), the boundaries of which remain uncertain. An initiative that will
      focus attention away from (mere) symptoms of the illness and toward its
      underlying neurobiological construct(s) is the Research Domain Criteria. A
      preliminary analysis from a large neurobiological study suggests that 3 distinct
      biological phenotypes underlie the clinical expression of 1 major psychosis. A
      firmer neurobiologically based foundation is needed to advance this field. 

PMID- 26300029
TI  - Development of New Psychopharmacological Agents for Depression and Anxiety.
AB  - Antidepressant and anxiolytic drug development has largely stalled. This article
      reviews novel current programs for developing depressants and anxiolytics.
      Biological bases are discussed for these, as are recent results. Problems
      encountered are reviewed. Recently announced failed programs for other
      antidepressants are then discussed with an eye toward uncovering possible common
      elements that may explain their failures. Lastly, possible solutions for
      improving the likelihood of the success of antidepressant/anxiolytic agents are
      discussed. 

PMID- 26300030
TI  - Personalized Medicine and Mood Disorders.
AB  - Some of the latest advances in personalized psychiatry with future research
      directions are discussed in this article. Many factors contribute to the
      phenotypic psychiatric profile in individual patients. These overlapping factors
      include but are not limited to genetics, epigenetics, central nervous system
      circuit alterations, family history, past personal history, environmental
      influences including early life stress, and more recent life stressors. The
      authors discuss the role of pharmacogenomics, particularly in the cytochrome P450
      enzyme system in relation to treatment response. Despite some promising advances
      in personalized medicine in psychiatry, it is still in its early phases of
      development. 

PMID- 26300031
TI  - Psychotherapy and Psychosocial Treatment: Recent Advances and Future Directions.
AB  - Psychotherapy and psychosocial treatment have been shown to be effective forms of
      treatment of a range of individual and complex comorbid disorders. The future
      role of psychotherapy and psychosocial treatment depends on several factors,
      including full implementation of mental health parity, correction of underlying
      false assumptions that shape treatment, payment priorities and research,
      identification and teaching of common factors or elements shared by effective
      psychosocial therapies, and adequate teaching of psychotherapy and psychosocial
      treatment. 

PMID- 26300032
TI  - A Shared Molecular and Genetic Basis for Food and Drug Addiction: Overcoming
      Hypodopaminergic Trait/State by Incorporating Dopamine Agonistic Therapy in
      Psychiatry.
AB  - This article focuses on the shared molecular and neurogenetics of food and drug
      addiction tied to the understanding of reward deficiency syndrome. Reward
      deficiency syndrome describes a hypodopaminergic trait/state that provides a
      rationale for commonality in approaches for treating long-term reduced dopamine
      function across the reward brain regions. The identification of the role of DNA
      polymorphic associations with reward circuitry has resulted in new understanding
      of all addictive behaviors. 

PMID- 26300033
TI  - Integrated Care at the Interface of Psychiatry and Primary Care: Prevention of
      Cardiovascular Disease.
AB  - Patients with mental illness, particularly serious mental illness, are more
      likely to suffer from common disorders without optimal treatment. Changes in
      preventive practice patterns cannot be fully realized on a large scale until
      clinicians are trained how to routinely provide this care. Psychiatrists may
      consider using preventive care strategies in the area of cardiovascular health,
      as cardiovascular disease is the most common cause of death and
      disproportionately affects patients with mental illness. At minimum,
      psychiatrists are well positioned to work collaboratively with primary care
      providers to address psychopathology that may interfere with adherence to the
      treatment plan. 

PMID- 26300034
TI  - The Next Big Thing in Child and Adolescent Psychiatry: Interventions to Prevent
      and Intervene Early in Psychiatric Illnesses.
AB  - The last two decades have marked tremendous progress in our ability to prevent
      and intervene early in psychiatric illnesses. The interventions described in this
      article range from established, empirically-supported treatments to creative
      interventions early in their development and deployment. Some of these
      interventions are low-technology programs delivered in social settings (such as
      schools), and some rely on sophisticated emerging technologies such as
      neuroimaging. This article reviews 4 preventative interventions: 1) The use of
      structural brain imaging to identify children at risk for familial depression who
      are most likely to benefit from preventative cognitive behavioral therapy 2) The
      Good Behavior Game, a school based program that, when implemented in 1st grade
      classrooms, cut the incidence of substance use disorders in students in half when
      those students were 19 years old, 3) The SPARX video game, which has the
      potential to be an accessible, appealing, and cost-effective treatment for the
      thousands of teens affected by mild to moderate depressive disorders, and 4)
      Intensive psychosocial treatments which can reduce the progression of from the
      ultra high risk state to the first episode psychosis by 50% over 12 months. All
      of these interventions have tremendous potential to reduce the suffering and
      disability caused by psychiatric illness to both children and adults. 

PMID- 26300036
TI  - Complex Trauma in Adolescents and Adults: Effects and Treatment.
AB  - Complex trauma involves multiple exposures to adverse events over the lifespan.
      Such experiences are associated with a variety of psychological outcomes,
      including a decreased threshold for the development of posttraumatic stress
      disorder as well as self-capacity problems and dysfunctional behaviors.
      Psychological interventions that increase affect regulation, support titrated
      processing of memories and cognitions, and emphasize the therapeutic relationship
      seem to be most helpful for complex trauma effects. Pharmacologic treatments have
      some efficacy in the treatment of the posttraumatic stress components of complex
      posttraumatic outcomes but are generally less successful in reducing self-related
      problems and symptoms. 

PMID- 26300037
TI  - Facing Violence - A Global Challenge.
AB  - Violence has been shown to be a global challenge resulting in long-lasting
      social, medical, and mental health sequelae. In this article, we focus on massive
      social violence, such as war and civil war. Social suffering and mental health
      problems related to violence as a global public health problem can be tackled
      only with a holistic approach that addresses the specific region, culture and
      group and the limited resources available in most countries. Research that can
      give a reliable assessment of complex long-term outcomes is still largely
      missing, and can be seen as a major and complex challenge for future study. 

PMID- 26300035
TI  - Clinical Advances in Geriatric Psychiatry: A Focus on Prevention of Mood and
      Cognitive Disorders.
AB  - The world population is aging at a rate unprecedented in human history, placing
      substantial pressure on health systems across the world along with concurrent
      rises in chronic diseases. In particular, rates of cognitive disorders and late
      life affective disorders are expected to increase. In tandem with aging, there
      are robust predictions suggesting that rates of age-related cognitive decline and
      dementia, and geriatric depression, will increase, with serious consequences.
      Clearly innovative prevention and treatment strategies are needed. This article
      reviews the latest promising clinical advances that hold promise for assisting
      the prevention and treatment of depression, cognitive decline, and dementia. 

PMID- 26300038
TI  - How Health Reform is Recasting Public Psychiatry.
AB  - This article reviews the fiscal, programmatic, clinical, and cultural forces of
      health care reform that are transforming the work of public psychiatrists. Areas
      of rapid change and issues of concern are discussed. A proposed health care
      reform agenda for public psychiatric leadership emphasizes (1) access to quality
      mental health care, (2) promotion of recovery practices in primary care, (3)
      promotion of public psychiatry values within general psychiatry, (4) engagement
      in national policy formulation and implementation, and (5) further development of
      psychiatric leadership focused on public and community mental health. 

PMID- 26300039
TI  - Telepsychiatry: Effective, Evidence-Based, and at a Tipping Point in Health Care
      Delivery?
AB  - Patient-centered health care questions how to deliver quality, affordable, and
      timely care in a variety of settings. Telemedicine empowers patients, increases
      administrative efficiency, and ensures expertise gets to the place it is most
      needed--the patient. Telepsychiatry or telemental health is effective, well
      accepted, and comparable to in-person care. E-models of care offer variety,
      flexibility, and positive outcomes in most settings, and clinicians are
      increasingly interested in using technology for care, so much so that
      telepsychiatry is now being widely introduced around the world.

PMID- 26300040
TI  - Where Are We, and Where Are We Going? An Insider's View....

PMID- 26300041
TI  - Metallic Sn spheres and SnO2@C core-shells by anaerobic and aerobic catalytic
      ethanol and CO oxidation reactions over SnO2 nanoparticles.
AB  - SnO2 has been studied intensely for applications to sensors, Li-ion batteries and
      solar cells. Despite this, comparatively little attention has been paid to the
      changes in morphology and crystal phase that occur on the metal oxide surface
      during chemical reactions. This paper reports anaerobic and aerobic ethanol and
      CO oxidation reactions over SnO2 nanoparticles (NPs), as well as the subsequent
      changes in the nature of the NPs. Uniform SnO2@C core-shells (10 nm) were formed
      by an aerobic ethanol oxidation reaction over SnO2 NPs. On the other hand,
      metallic Sn spheres were produced by an anaerobic ethanol oxidation reaction at
      450  degrees C, which is significantly lower than that (1200  degrees C) used in
      industrial Sn production. Anaerobic and aerobic CO oxidation reactions were also
      examined. The novelty of the methods for the production of metallic Sn and SnO2@C
      core-shells including other anaerobic and aerobic reactions will contribute
      significantly to Sn and SnO2-based applications. 

PMID- 26300042
TI  - Efficient generation of gene-modified human natural killer cells via
      alpharetroviral vectors.
AB  - Natural killer (NK) cells play an important role in tumor immunotherapy with
      their unique capability of killing transformed cells without the need for prior
      sensitization and without major histocompatibility complex (MHC)/peptide
      restriction. However, tumor cells can escape NK cell cytotoxicity by various
      tumor immune escape mechanisms. To overcome these escape mechanisms, NK cells can
      be modified to express chimeric antigen receptors (CARs), enhancing their tumor
      specific cytotoxicity. To determine the most efficacious method to modify human
      NK cells, we compared different retroviral vector systems, retroviral
      pseudotypes, and transduction protocols. Using optimized transduction conditions,
      the highest transduction levels (up to 60%) were achieved with alpharetroviral
      vectors. Alpharetroviral-modified primary human NK cells exhibited no alteration
      in receptor expression and had similar degranulation activity as untransduced NK
      cells, thus demonstrating that alpharetroviral modification did not negatively
      affect NK cell cytotoxicity. Transduction of NK cells with an alpharetroviral
      vector containing a CD19 CAR expression cassette selectively enhanced NK cell
      cytotoxicity towards CD19-expressing leukemia cells, achieving nearly complete
      elimination of leukemia cells after 48 h. Taken together, alpharetroviral vectors
      are promising tools for NK cell-mediated cancer immunotherapy applications. KEY
      MESSAGES: Efficient modification of human NK cells using alpharetroviral vectors.
      Anti-CD19-CAR-NK cells exhibited improved cytotoxicity towards CD19(+) leukemia
      cells. Alpharetroviral vectors are promising tools for immunotherapy applications
      using NK cells.

PMID- 26300043
TI  - Renal oxygenation during haemorrhage is not aggravated by angiotensin II AT1
      receptor blockade.

PMID- 26300044
TI  - Dementia in western Europe: epidemiological evidence and implications for policy
      making.
AB  - Dementia is receiving increasing attention from governments and politicians.
      Epidemiological research based on western European populations done 20 years ago
      provided key initial evidence for dementia policy making, but these estimates are
      now out of date because of changes in life expectancy, living conditions, and
      health profiles. To assess whether dementia occurrence has changed during the
      past 20-30 years, investigators of five different studies done in western Europe
      (Sweden [Stockholm and Gothenburg], the Netherlands [Rotterdam], the UK
      [England], and Spain [Zaragoza]) have compared dementia occurrence using
      consistent research methods between two timepoints in well-defined geographical
      areas. Findings from four of the five studies showed non-significant changes in
      overall dementia occurrence. The only significant reduction in overall prevalence
      was found in the study done in the UK, powered and designed explicitly from its
      outset to detect change across generations (decrease in prevalence of 22%;
      p=0.003). Findings from the study done in Zaragoza (Spain) showed a significant
      reduction in dementia prevalence in men (43%; p=0.0002). The studies estimating
      incidence done in Stockholm and Rotterdam reported non-significant reductions.
      Such reductions could be the outcomes from earlier population-level investments
      such as improved education and living conditions, and better prevention and
      treatment of vascular and chronic conditions. This evidence suggests that
      attention to optimum health early in life might benefit cognitive health late in
      life. Policy planning and future research should be balanced across primary
      (policies reducing risk and increasing cognitive reserve), secondary (early
      detection and screening), and tertiary (once dementia is present) prevention.
      Each has their place, but upstream primary prevention has the largest effect on
      reduction of later dementia occurrence and disability.

PMID- 26300045
TI  - Small Field-of-view single-shot EPI-DWI of the prostate: Evaluation of spatially
      tailored two-dimensional radiofrequency excitation pulses.
AB  - PURPOSE: Spatially-tailored (RF) excitation pulses in echo-planar imaging (EPI),
      combined with a decreased FOV in the phase-encoding direction, enable a reduction
      of k-space acquisition lines, which shortens the echo train length (ETL) and
      reduces susceptibility artifacts. The purpose of this study was to evaluate the
      image quality of a zoomed EPI (z-EPI) sequence in diffusion-weighted imaging
      (DWI) of the prostate in comparison to a conventional single-shot EPI using
      single-channel (c-EPI1) and multi-channel (c-EPI2) RF excitation, with and
      without use of an endorectal coil. MATERIALS AND METHODS: 33 consecutive patients
      (mean age: 61 +/- 9 years; mean PSA: 8.67+/-6.23 ng/ml) with examinations between
      10/2012 and 02/2014 were analyzed in this retrospective study. In 26 of 33
      patients the initial multiparametric (mp)-MRI was performed on a whole-body 3T
      scanner (Magnetom Trio, Siemens, Erlangen, Germany) using an endorectal coil (c
      (conventional)-EPI1). Zoomed-EPI (Z-EPI) examinations of these patients and a
      complete mp-MRI protocol including c-EPI2 of 7 additional patients were carried
      out on another 3T wb MR scanner with two-channel dynamic parallel transmit
      capability (Magnetom Skyra with TimTX TrueShape, Siemens). For z-EPI, the one
      dimensional spatially selective RF excitation pulse was replaced by a two
      dimensional RF pulse. Degree of image blur and susceptibility artifacts (0=not
      present to 3= non-diagnostic), maximum image distortion (mm), apparent diffusion
      coefficient (ADC) values, as well as overall scan preference were evaluated. SNR
      maps were generated to compare c-EPI2 and z-EPI. RESULTS: Overall image quality
      of z-EPI was preferred by both readers in all examinations with a single
      exception. Susceptibility artifacts were rated significantly lower on z-EPI
      compared to both other methods (z-EPI vs c-EPI1: p<0.01; z-EPI vs c-EPI2: p<0.01)
      as well as image blur (z-EPI vs c-EPI1: p<0.01; z-EPI vs c-EPI2: p<0.01). Image
      distortion was not statistically significantly reduced with z-EPI (z-EPI vs c
      EPI1: p=0.12; z-EPI vs c-EPI2: p=0.42). Interobserver agreement for ratings of
      susceptibility artifacts, image blur and overall scan preference was good. SNR
      was higher for z-EPI than for c-EPI1 (n=1). CONCLUSION: Z-EPI leads to
      significant improvements in image quality and artifacts as well as image blur
      reduction improving prostate DWI and enabling accurate fusion with conventional
      sequences. The improved fusion could lead to advantages in the field of MRI
      guided biopsy suspicous lesions and performance of locally ablative procedures
      for prostate cancer.

PMID- 26300046
TI  - Assessment of Left Atrial Mechanics in Patients with Preexcitation Syndrome
      Scheduled for Catheter Ablation.
AB  - OBJECTIVES: We aimed to test the left atrial (LA) mechanics and contraction
      synchrony by 2D strain imaging, in patients with Wolff-Parkinson-White (WPW)
      syndrome, before and after radiofrequency catheter ablation (RFCA). METHODS:
      Study population consisted of 25 patients with WPW scheduled for RFCA and 30
      healthy controls. The peak LA strain at the end of the ventricular systole (LAs
      strain) and the LA strain with LA contraction (LAa Strain) were obtained. To
      assess LA dyssynchrony, septal versus lateral wall time-to-peak strain
      measurements were measured. RESULTS: There was no difference between the patients
      with WPW and control subjects with regard to peak LAs and LAa strain. Patients
      with WPW demonstrated higher global time-to-peak LAs and LAa strain values
      compared with the control group. Peak LAs strain and LAa strain values, measured
      before and after the RF ablation of the accessory pathway, were comparable (34.3
      +/- 3.92 vs. 34.6 +/- 3.2, P = 0.816, 14.7 +/- 2.8 vs. 15.3 +/- 2.3, P = 0.052,
      respectively). Global time-to-peak LAs and LAa strain measurements were
      significantly shorter after the RFCA compared with the values obtained before the
      RFCA. However, septo-lateral times to peak LA strain differences were found to be
      comparable in both WPW versus control and pre- versus postablation groups.
      CONCLUSION: LA mechanical function assessed by 2D strain imaging was comparable
      between patients with WPW and control subjects. Patients with WPW had more
      prominent LA dyssynchrony during atrial pump phase as compared with the controls,
      a condition which could not improve after successful elimination of the accessory
      pathway by RFCA.

PMID- 26300047
TI  - Engineering a Lysine-ON Riboswitch for Metabolic Control of Lysine Production in
      Corynebacterium glutamicum.
AB  - Riboswitches are natural RNA elements that regulate gene expression by binding a
      ligand. Here, we demonstrate the possibility of altering a natural lysine-OFF
      riboswitch from Eschericia coli (ECRS) to a synthetic lysine-ON riboswitch and
      using it for metabolic control. To this end, a lysine-ON riboswitch library was
      constructed using tetA-based dual genetic selection. After screening the library,
      the functionality of the selected lysine-ON riboswitches was examined using a
      report gene, lacZ. Selected lysine-ON riboswitches were introduced into the lysE
      gene (encoding a lysine transport protein) of Corynebacterium glutamicum and used
      to achieve dynamic control of lysine transport in a recombinant lysine-producing
      strain, C. glutamicum LPECRS, which bears a deregulated aspartokinase and a
      lysine-OFF riboswitch for dynamic control of the enzyme citrate synthase. Batch
      fermentation results of the strains showed that the C. glutamicum LPECRS strain
      with an additional lysine-ON riboswitch for the control of lysE achieved a 21%
      increase in the yield of lysine compared to that of the C. glutamicum LPECRS
      strain and even a 89% increase in yield compared to that of the strain with
      deregulated aspartokinase. This work provides a useful approach to generate
      lysine-ON riboswitches for C. glutamicum metabolic engineering and demonstrates
      for the first time a synergetic effect of lysine-ON and -OFF riboswitches for
      improving lysine production in this industrially important microorganism. The
      approach can be used to dynamically control other genes and can be applied to
      other microorganisms. 

PMID- 26300049
TI  - Exploring Parental Influence on the Progression of Alcohol Use in Mexican
      Heritage Youth: a Latent Transition Analysis.
AB  - Mexican-heritage youth are members of the fastest growing minority group and are
      at particular risk for substance use including alcohol consumption. Youth face
      numerous risk factors including positive descriptions of substance use on media
      and peer offers that are potentially ameliorated by parental anti-substance use
      socialization efforts. Guided by primary socialization theory and the theory of
      planned behavior, the present study posited eight research questions to identify
      discrete subgroups/patterns of Mexican-heritage youth alcohol use behavior and
      parental influence on youth outcomes. Longitudinal survey data (n = 1147) from
      youth in 29 public schools located in Phoenix, Arizona, were collected over 3
      years. Latent class and transition analyses identified four discrete subgroups
      characterized by response patterns of alcohol use behaviors and perceptions in
      Mexican-heritage youth: (1) non-drinker, (2) potential drinker, (3) experimenter,
      and (4) regular drinker. Targeted parent-child communication about alcohol and
      parental monitoring were found to be significant predictors for youth alcohol
      use. Research implications and future directions are suggested.

PMID- 26300048
TI  - Functional assignment to positively selected sites in the core type III effector
      RipG7 from Ralstonia solanacearum.
AB  - The soil-borne pathogen Ralstonia solanacearum causes bacterial wilt in a broad
      range of plants. The main virulence determinants of R. solanacearum are the type
      III secretion system (T3SS) and its associated type III effectors (T3Es),
      translocated into the host cells. Of the conserved T3Es among R. solanacearum
      strains, the Fbox protein RipG7 is required for R. solanacearum pathogenesis on
      Medicago truncatula. In this work, we describe the natural ripG7 variability
      existing in the R. solanacearum species complex. We show that eight
      representative ripG7 orthologues have different contributions to pathogenicity on
      M. truncatula: only ripG7 from Asian or African strains can complement the
      absence of ripG7 in GMI1000 (Asian reference strain). Nonetheless, RipG7 proteins
      from American and Indonesian strains can still interact with M. truncatula SKP1
      like/MSKa protein, essential for the function of RipG7 in virulence. This
      indicates that the absence of complementation is most likely a result of the
      variability in the leucine-rich repeat (LRR) domain of RipG7. We identified 11
      sites under positive selection in the LRR domains of RipG7. By studying the
      functional impact of these 11 sites, we show the contribution of five positively
      selected sites for the function of RipG7CMR15 in M. truncatula colonization. This
      work reveals the genetic and functional variation of the essential core T3E RipG7
      from R. solanacearum. This analysis is the first of its kind on an essential
      disease-controlling T3E, and sheds light on the co-evolutionary arms race between
      the bacterium and its hosts. 

PMID- 26300050
TI  - Scribble dictates orderly stem cell fate.

PMID- 26300051
TI  - Fragments and hot spots in drug discovery.

PMID- 26300052
TI  - A bacterial toxin that cleaves Ras oncoprotein.

PMID- 26300053
TI  - Antimicrobial peptides targeting bacterial ribosome.

PMID- 26300054
TI  - Unexpected insights for anti-EGFR cancer therapy.

PMID- 26300055
TI  - PKC-delta/PKC-alpha activity balance regulates the lethal effects of cisplatin.
AB  - Cisplatin is commonly employed in therapy of mesothelioma but its efficacy is
      limited and the mechanisms by which induces its effects are not clearly
      understood. PKCs can regulate cisplatin sensitivity. PKCs effects on cellular
      sensitivity/resistance depend on the pattern of active PKC isozymes as well as on
      cellular context. The present study was undertaken to determine if specific PKC
      isoforms regulate cisplatin-induced apoptosis in the human mesothelioma ZL55
      cells. Cells were treated with cisplatin at various concentrations and for
      different incubation periods. Cytotoxicity assays and Western blottings of
      various proteins involved in apoptosis and survival were then performed. Exposure
      of ZL55 cells to cisplatin at concentrations ranging from 1 to 200 MUM resulted
      in a dose-dependent inhibition of cell survival and the activation of the
      mitochondrial apoptotic pathway. Cisplatin activated full-length PKC-delta and
      generated a PKC-delta fragment. PKC-delta inhibition (by PKC-delta-siRNA)
      decreased ZL55 cell apoptosis. Full-length PKC-delta translocated to the nucleus
      and activated caspase-3 expression, whereas PKC-delta fragment preferentially
      localized to mitochondria. Cisplatin also provoked the generation of reactive
      oxygen species (ROS) by NADPH oxidase. ROS increment was responsible for the PKC
      alpha activation that provoked EGFR transactivation and consequential
      phosphorylation of ERK1/2. The inhibition of this pathway at various level (PKC
      alpha, EGFR or ERK1/2) increased cisplatin-induced cytotoxicity. The results
      suggest that PKC-delta is an essential part of the apoptotic program in
      mesothelioma cells, whereas PKC-alpha mediates a pro-survival response to
      cisplatin. 

PMID- 26300056
TI  - Dinaciclib, a cyclin-dependent kinase inhibitor, is a substrate of human ABCB1
      and ABCG2 and an inhibitor of human ABCC1 in vitro.
AB  - Dinaciclib is a novel cyclin-dependent kinase inhibitor (CDKI) with significant
      activity against various cancers in vitro and in vivo. ABC efflux transporters
      play an important role in drug disposition and are responsible for multidrug
      resistance in cancer cells. Inhibitors and substrates of these transporters may
      participate in pharmacokinetic drug-drug interactions (DDIs) that alter drug
      disposition during pharmacotherapy. To assess such risks associated with
      dinaciclib we evaluated its possible effects on efflux activities of ABCB1, ABCC1
      and ABCG2 transporters in vitro. Monolayer transport, XTT cell proliferation,
      ATPase and intracellular accumulation assays were employed. Here, we show that
      the transport ratio of dinaciclib was far higher across monolayers of MDCKII
      ABCB1 and MDCKII-ABCG2 cells than across MDCKII parental cell layers,
      demonstrating that dinaciclib is a substrate of ABCB1 and ABCG2. In addition,
      overexpression of ABCB1, ABCG2 and ABCC1 conferred resistance to dinaciclib in
      MDCKII cells. In ATPase assays, dinaciclib decreased stimulated ATPase activity
      of ABCB1, ABCG2 and ABCC1, confirming it has interactive potential toward all
      three transporters. Moreover, dinaciclib significantly inhibited ABCC1-mediated
      efflux of daunorubicin (EC50=18 MUM). The inhibition of ABCC1 further led to a
      synergistic effect of dinaciclib in both MDCKII-ABCC1 and human cancer T47D
      cells, when applied in combination with anticancer drugs. Taken together, our
      results suggest that ABC transporters can substantially affect dinaciclib
      transport across cellular membranes, leading to DDIs. The DDIs of dinaciclib with
      ABCC1 substrate chemotherapeutics might be exploited in novel cancer therapies.

PMID- 26300057
TI  - Silencing of PKC-alpha, TRPC1 or NF-kappaB expression attenuates cisplatin
      induced ICAM-1 expression and endothelial dysfunction.
AB  - Platinum-based chemotherapy has been associated with increased long-term
      cardiovascular events. Also noteworthy is the accumulating awareness of early
      vascular toxicity occurring at the time of chemotherapy or immediately
      thereafter. The objective of the study was to delineate the molecular mechanisms
      associated with the early vascular toxicity and test the molecular silencing
      approach towards attenuating the endothelial dysfunction during platinum-based
      chemotherapy. Human umbilical vein endothelial cells (HUVECs) were treated with
      varying concentrations of cisplatin (1.0-10.0MUg/ml) or vehicle control (0.1%
      dimethyl sulfoxide) for monitoring the changes in Intercellular adhesion molecule
      1 (ICAM-1) mRNA and protein expression viz. a viz. altered activation of protein
      kinase C (PKC) isoforms, transient receptor potential channel (TRPC) 1
      expression, Nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NF
      kappaB), Store Operated Ca(2+) Entry (SOCE) in cisplatin-induced endothelial
      permeability and adherence of the activated endothelial cells to human monocyte
      like U937 cells. Silencing of either PKC-alpha, TRPC1 or p65 subunit of NF
      kappaB, all resulted in significant alleviation of cisplatin-induced endothelial
      dysfunction. At concentrations >=8MUg/ml, cisplatin induced a significant
      increase in the expression of ICAM-1 mRNA as well as protein. This was mediated
      by changes in PKC-alpha membrane translocation, NF-kappaB activation, increased
      expression as well as phosphorylation of TRPC1 and enhanced SOCE, leading to
      hyperpermeability and leakage of albumin. Increased adherence of U937 monocytes
      to cisplatin-activated endothelial cells was evident. Cisplatin challenge
      activates PKC-alpha, which in turn phosphorylated TRPC1 resulting in enhanced
      Ca(2+) entry. Increased Ca(2+) flux is required for activation of NF-kappaB and
      ICAM-1 expression. Enhanced ICAM-1 expression promotes monocyte binding to
      endothelial cells and increased endothelial hyperpermeability. 

PMID- 26300058
TI  - Role of sex steroids and their receptors in human preterm infants: Impacts on
      future treatment strategies for cerebral development.
AB  - Preterm birth is a major risk factor for cerebral complications, such as
      hemorrhage or periventricular leukomalacia, which lead to lifelong
      neurodevelopmental deficits. Hypoxia/ischemia, inflammation, hyperoxia, and
      prematurity itself contribute to the extent of impaired neurodevelopment. Preterm
      birth leads to disruption of the placental supply of estrogens and progesterone.
      Postnatally, the plasma levels of estrogens and progesterone drop 100-fold.
      Preterm infants are deprived of the placental supply of these hormones for up to
      sixteen weeks. Thus, supplementation of estradiol and progesterone to mimic
      intrauterine conditions may potentially improve a premature infants extrauterine
      development and help protect the brain against neurological complications.
      However, preliminary clinical studies did not find improved outcomes except for a
      trend towards less cerebral palsy. The decrease in estrogen and progesterone
      concentrations is accompanied by persistent, high postnatal production of fetal
      zone steroids, mainly dehydroepiandrosterone, which serve as precursors for
      maternal estrogen synthesis during pregnancy. This commentary will combine
      knowledge from endocrinology, pharmacology, and neonatology to explain the
      discrepancies between promising animal models and clinical findings. Most
      important targets will be classical and non-classical estrogen receptors, which
      interact differently-not only with estrogens but also with fetal zone steroids.
      The fetal zone is unique among humans and higher primates. Therefore, a clearly
      defined model is required to study the role of sex steroids and their receptors
      before further clinical studies begin. 

PMID- 26300059
TI  - cCMP causes caspase-dependent apoptosis in mouse lymphoma cell lines.
AB  - cCMP is a cyclic pyrimidine nucleotide which binds to and activates cAMP
      dependent protein kinase (PKA) and cGMP-dependent protein kinase (PKG). In S49
      lymphoma cells, cAMP induces apoptosis via PKA. In our present study, we examined
      the effect of cCMP on apoptosis in S49 mouse lymphoma cells and in PKA-deficient
      S49kin(-)cells. These two cell lines also lack PKG, hyperpolarization-activated
      cyclic nucleotide-gated channels 2 and 4 (HCN2 and HCN4) as assessed by real-time
      PCR. The cell-permeable analog cCMP-AM induced PKA- and PKG-independent apoptosis
      in S49 cells. In contrast, exchange protein activated by cAMP (Epac) activation
      did not induce apoptosis. cCMP induced caspase-dependent apoptosis via the
      intrinsic pathway, led to cytochrome c release from mitochondria and also
      activated the ER stress pathway. On the contrary, the extrinsic apoptotic pathway
      was not involved. Autophagy was not detectable after treatment with cCMP-AM in
      both cell lines. cAMP-AM, cGMP-AM, cUMP-AM as well as the cyclic nucleotides
      lacking the acetoxymethylester (AM)-group had no effect. cCMP-AM altered gene
      expression of the apoptotic-relevant gene Gadd45alpha and the immediate early
      response genes cFos and Nr4A1 in S49 wild-type (wt) cells. In conclusion, cCMP
      induces apoptosis of S49 lymphoma cells, independently of hitherto known cCMP
      target proteins. 

PMID- 26300060
TI  - HIV-1 protease substrate-groove: Role in substrate recognition and inhibitor
      resistance.
AB  - A key target in the treatment of HIV-1/AIDS has been the viral protease. Here we
      first studied in silico the evolution of protease resistance. Primary active site
      resistance mutations were found to weaken interactions between protease and both
      inhibitor and substrate P4-P4' residues. We next studied the effects of secondary
      resistance mutations, often distant from the active site, on protease binding to
      inhibitors and substrates. Those secondary mutations contributed to the rise of
      multi-drug resistance while also enhancing viral replicative capacity. Here many
      secondary resistance mutations were found in the HIV-1 protease substrate
      grooves, one on each face of the symmetrical protease dimer. The protease active
      site binds substrate P4-P4' residues, while the substrate-groove allows the
      protease to bind residues P12-P5/P5'-P12', for a total of twenty-four residues.
      The substrate-groove secondary resistance mutations were found to compensate for
      the loss of interactions between the inhibitor resistant protease active site and
      substrate P4-P4' residues, due to primary resistance mutations, by increasing
      interactions with substrate P12-P5/P5'-P12' residues. In vitro experiments
      demonstrated that a multi-drug resistant protease with substrate-groove
      resistance mutations was slower than wild-type protease in cleaving a peptide
      substrate, which did not allow for substrate-groove interactions, while it had
      similar activity as wild-type protease when using a Gag polyprotein in which
      cleavage-site P12-P5/P5'-P12' residues could be bound by the protease substrate
      grooves. When the Gag MA/CA cleavage site P12-P5/P5'-P12' residues were mutated
      the multi-drug resistant protease cleaved the mutant Gag significantly slower,
      indicating the importance of the protease S-grooves in binding to substrate. 

PMID- 26300061
TI  - Intramolecular hydrogen bonding in the polyextremophilic short-chain
      dehydrogenase from the archaeon Thermococcus sibiricus and its close structural
      homologs.
AB  - The short-chain alcohol dehydrogenase from the archaeon Thermococcus sibiricus
      (TsAdh319) exhibits adaptation to different kinds of stress: high temperature,
      high salinity, and the presence of organic solvents and denaturants. Previously a
      comparison of TsAdh319 with close structural homologs revealed an abnormally
      large number of charged residues on the surface of TsAdh319 tetramer. We further
      focused on the analysis of hydrogen bonding of TsAdh319 and its structural
      homologs from thermophilic and mesophilic organisms as a structural factor of
      adaptation to extreme environment. The calculation and analysis of the dynamics
      of hydrogen bonds of different kind were performed. In particular, the
      intramolecular hydrogen bonds of different kind according to their location and
      the type of a.a. residues involved in the bond were analyzed. TsAdh319 showed the
      greatest contribution of charged residues to the formation of surface hydrogen
      bonds, inner hydrogen bonding, and the bonds between different subunits compared
      to its structural homologs. Molecular dynamics simulations revealed that, of
      three enzyme molecules analyzed, TsAdh319 shows the least change in the number of
      hydrogen bonds of different kinds upon a temperature shift from 27 to 85  degrees
      C. The greatest changes were observed for a homologous enzyme from a mesophilic
      host. Only guanidine hydrochloride being a charged agent was able to deactivate
      TsAdh319. We suggest that the percentage of charged residues plays a key role in
      the resistance of TsAdh319 to environmental stress. The analysis shows that salt
      bridges in TsAdh319 serve as a universal instrument of stabilization under
      different extreme conditions. 

PMID- 26300062
TI  - Immediately provisionalized OsseoSpeed(TM) Profile implants inserted into
      extraction sockets: 3-year results.
AB  - OBJECTIVES: A sloped shoulder might improve the congruence between extraction
      socket and dental implant and may add to a better circumferential support of the
      peri-implant structures. Therefore, this study evaluates the 3-year clinical
      outcome (survival and success rates, marginal bone levels, and Pink Esthetic
      Score (PES)) of immediately inserted and provisionalized OsseoSpeed(TM) Profile
      implants in the anterior maxilla. MATERIAL AND METHODS: Twenty-one implants were
      inserted in 16 patients. All implants were immediately placed into extraction
      sites with and without facial bone deficiencies. A flapless procedure was
      utilized, and the implants were provisionalized immediately. Facial gaps were
      grafted with autogenous bone chips from the mandibular ramus. Implant survival
      and success, the interproximal bone levels, the thickness of the facial bony
      wall, and the PES were evaluated. RESULTS: After a mean follow-up period of 43
      months, 19 implants were still in function. One patient with 1 implant did not
      follow the study protocol (dropout) and 1 implant was lost at 10 weeks.
      Interproximal marginal bone levels measured -0.2 +/- 0.4 mm (range, -1.0-0.4 mm)
      apical to the implant shoulder. The mean PES ratings were 11.9 +/- 1.4 (range, 8
      14) at the final examination. CONCLUSIONS: Clinical and radiographic results
      provide evidence that sloped implants can preserve the marginal bone
      circumferentially and are able to maintain soft tissue esthetics when inserted
      and provisionalized immediately, even in the presence of facial bony wall
      defects.

PMID- 26300063
TI  - Successful treatment of both double minute of C-MYC and BCL-2 rearrangement
      containing large B-cell lymphoma with subsequent unfortunate development of
      therapy-related acute myeloid leukemia with t(3;3)(q26.2;q21).
AB  - Double minute chromosomes (DMs), although relatively frequently encountered in
      solid tumors, are rare in hematologic neoplasms such as acute myeloid leukemia
      (AML), and even rarer in lymphoid neoplasms. t(3;3)(q26.2;q21) is a very rare
      genetic alteration observed in myeloid neoplasm. Herein we report an interesting
      and unique case of concomitant C-MYC DMs and t(14;18)-containing large B-cell
      lymphoma, which was successfully treated with R-hyper-CVAD; unfortunately, the
      patient has developed a therapy-related AML (t-AML) 2 years since the start of
      his lymphoma treatment. His t-AML contains both t(3;3)(q26.2;q21) and monosomy 7,
      and the patient died of AML 10 months after the initial diagnosis of t-AML
      despite clinical remission. To the best of our knowledge, this is the first
      reported case of C-MYC DM-containing de novo large B-cell lymphoma, which was
      successfully treated with complete remission, but unfortunately died of t-AML
      harboring t(3;3)(q21;q26). 

PMID- 26300064
TI  - In vivo 808 nm image-guided photodynamic therapy based on an upconversion
      theranostic nanoplatform.
AB  - A new strategy for efficient in vivo image-guided photodynamic therapy (PDT) has
      been demonstrated utilizing a ligand-exchange constructed upconversion-C60
      nanophotosensitizer. This theranostic platform is superior to the currently
      reported nanophotosensitizers in (i) directly bonding photosensitizer C60 to the
      surface of upconversion nanoparticles (UCNPs) by a smart ligand-exchange
      strategy, which greatly shortened the energy transfer distance and enhanced the
      (1)O2 production, resulting in the improvement of the therapeutic effect; (ii)
      realizing in vivo NIR 808 nm image-guided PDT with both excitation (980 nm) and
      emission (808 nm) light falling in the biological window of tissues, which
      minimized auto-fluorescence, reduced light scatting and improved the imaging
      contrast and depth, and thus guaranteed noninvasive diagnostic accuracy. In vivo
      and ex vivo tests demonstrated its favorable bio-distribution, tumor-selectivity
      and high therapeutic efficacy. Owing to the effective ligand exchange strategy
      and the excellent intrinsic photophysical properties of C60, (1)O2 production
      yield was improved, suggesting that a low 980 nm irradiation dosage (351 J cm(
      2)) and a short treatment time (15 min) were sufficient to perform NIR (980 nm)
      to NIR (808 nm) image-guided PDT. Our work enriches the understanding of UCNP
      based PDT nanophotosensitizers and highlights their potential use in future NIR
      image-guided noninvasive deep cancer therapy. 

PMID- 26300065
TI  - Insulin resistance or hypersecretion? The betaIG picture revisited.
AB  - Mathematical models of glucose, insulin and pancreatic beta-cell mass dynamics
      are essential to our understanding of the physiological basis of the development
      of type 2 diabetes. The classical view of diabetes is that the disease develops
      due to insulin insufficiency. An alternate viewpoint that has recently staged a
      revival is that diabetogenesis is a hypersecretion disorder. A prominent model of
      diabetes progression is the betaIG model due to Topp and coworkers. Here we study
      two new variants of the Topp model, which we name "Topp-IR" and "Topp-HS". Topp
      IR is a model in which increasing insulin resistance is sufficient to drive a
      system away from health towards hyperglycemia. Topp-HS describes the
      hypersecretion model in mathematical terms. We thus show that the hypersecretion
      hypothesis is theoretically sound, and is therefore a potential route to
      diabetes. On the basis of insights derived from modeling, we clarify several
      subtleties of that argument, including postulating a central role for transient
      insulin peaks in driving insulin resistance. 

PMID- 26300066
TI  - Lift vs. drag based mechanisms for vertical force production in the smallest
      flying insects.
AB  - We used computational fluid dynamics to determine whether lift- or drag-based
      mechanisms generate the most vertical force in the flight of the smallest
      insects. These insects fly at Re on the order of 4-60 where viscous effects are
      significant. Detailed quantitative data on the wing kinematics of the smallest
      insects is not available, and as a result both drag- and lift-based strategies
      have been suggested as the mechanisms by which these insects stay aloft. We used
      the immersed boundary method to solve the fully-coupled fluid-structure
      interaction problem of a flexible wing immersed in a two-dimensional viscous
      fluid to compare three idealized hovering kinematics: a drag-based stroke in the
      vertical plane, a lift-based stroke in the horizontal plane, and a hybrid stroke
      on a tilted plane. Our results suggest that at higher Re, a lift-based strategy
      produces more vertical force than a drag-based strategy. At the Re pertinent to
      small insect hovering, however, there is little difference in performance between
      the two strategies. A drag-based mechanism of flight could produce more vertical
      force than a lift-based mechanism for insects at Re<5; however, we are unaware of
      active fliers at this scale. 

PMID- 26300067
TI  - Front propagation speeds of T7 virus mutants.
AB  - We propose a new reaction-diffusion model with an eclipse time to study the
      spread of viruses on bacterial populations. This new model is both biologically
      and physically sound, unlike previous ones. We determine important parameter
      values from experimental data, such as the one-step growth. We verify the
      proposed model by comparing theoretical and experimental data of the front
      propagation speed for several T7 virus strains. 

PMID- 26300068
TI  - An improved acquaintance immunization strategy for complex network.
AB  - The acquaintance immunization strategy is a common strategy to suppress epidemic
      on complex network which achieves a seemingly perfect balance between cost and
      effectiveness compared with other canonical immunization strategies. However, the
      acquaintance immunization strategy fails to take the time-varying factor and
      local information of nodes into consideration, which limits its effectiveness in
      some specific network topology. Our improved immunization strategy is based on a
      new mathematical model Network Structure Index (NSI), which digs deep to measure
      the connection property and surrounding influence of a node's neighbor nodes to
      better determine the importance of nodes during immunization. Both mathematical
      derivation and the simulation program tested on various network topology support
      our idea that this improved acquaintance immunization strategy protects more
      nodes from infection and immunizes important nodes more efficiently than the
      original strategies. As to say, our strategy has more adaptability and achieves a
      more reasonable balanced point between cost and effectiveness.

PMID- 26300069
TI  - Progressive alignment of genomic signals by multiple dynamic time warping.
AB  - This paper presents the utilization of progressive alignment principle for
      positional adjustment of a set of genomic signals with different lengths. The new
      method of multiple alignment of signals based on dynamic time warping is tested
      for the purpose of evaluating the similarity of different length genes in
      phylogenetic studies. Two sets of phylogenetic markers were used to demonstrate
      the effectiveness of the evaluation of intraspecies and interspecies genetic
      variability. The part of the proposed method is modification of pairwise
      alignment of two signals by dynamic time warping with using correlation in a
      sliding window. The correlation based dynamic time warping allows more accurate
      alignment dependent on local homologies in sequences without the need of scoring
      matrix or evolutionary models, because mutual similarities of residues are
      included in the numerical code of signals. 

PMID- 26300070
TI  - On probabilistic certification of combined cancer therapies using strongly
      uncertain models.
AB  - This paper proposes a general framework for probabilistic certification of cancer
      therapies. The certification is defined in terms of two key issues which are the
      tumor contraction and the lower admissible bound on the circulating lymphocytes
      which is viewed as indicator of the patient health. The certification is viewed
      as the ability to guarantee with a predefined high probability the success of the
      therapy over a finite horizon despite of the unavoidable high uncertainties
      affecting the dynamic model that is used to compute the optimal scheduling of
      drugs injection. The certification paradigm can be viewed as a tool for tuning
      the treatment parameters and protocols as well as for getting a rational use of
      limited or expensive drugs. The proposed framework is illustrated using the
      specific problem of combined immunotherapy/chemotherapy of cancer. 

PMID- 26300072
TI  - The first hyperpolarizability of nitrobenzene in benzene solutions: investigation
      of the effects of electron correlation within the sequential QM/MM approach.
AB  - The first hyperpolarizability of nitrobenzene in benzene solutions is evaluated
      by adopting the sequential-Quantum Mechanics/Molecular Mechanics approach at
      different correlated wavefunction and density functional theory levels of
      approximation in order to compare these methods for predicting the solvent
      effects and in particular the effects of nitrobenzene concentration, which
      modifies the polarization field due to the surrounding. The liquid configurations
      are generated using Monte Carlo simulations and the surrounding molecules are
      represented by point charges, defining an electrostatic embedding. At all levels
      of approximation, the higher the concentration in nitrobenzene, the larger the
      first hyperpolarizability of the targeted molecule. At optical frequencies
      (lambda = 1064 nm), for the whole range of concentrations, increasing the amount
      of Hartree-Fock exchange in the exchange-correlation functional leads to the
      following observations (i) beta? and betaHRS decrease attaining a minimum at the
      HF level, (ii) the octupolar component to betaHRS increases, (iii) the HRS
      betasolv/betaisol ratio increases, and (iv) the EFISHG betasolv/betaisol ratio
      displays a less systematic behavior. Considering the static properties, for which
      reference CCSD(T) values have been evaluated, M05-2X, LC-BLYP (MU = 0.33), and
      M11 are the most reliable exchange-correlation functionals for predicting both
      betaHRS and its evolution as a function of the nitrobenzene concentration whereas
      in the case of beta?, these are M05-2X, LC-BLYP (MU = 0.28 and 0.33), and CAM
      B3LYP. 

PMID- 26300073
TI  - Examination of the Sequence between Laser Printing and Rollerball Pen Writing
      Without an Intersecting Stroke.
AB  - Examining the sequences of printing and writing is a significant method of
      determining the authenticity and validity of documents. Forensic document
      examiners have extensively studied crossing lines, which has produced useful
      information. However, the sequence for laser printing and rollerball pen writing
      without crossing strokes has not been studied. To solve this problem, volunteers
      were invited to write characters on A4 paper with different rollerball pens using
      two sequences. Four laser printers applied print to these sheets, and the
      materials were examined using an Optem A-Zoom2 video tomography microscope.
      Consequently, distinguishing features were noted between the materials produced
      in both sequences. These features might provide a scientific basis for accurately
      determining the sequence between laser printing and rollerball pen writing in the
      absence of intersecting strokes.

PMID- 26300071
TI  - Synergistic immunotherapeutic effects of Lycium barbarum polysaccharide and
      interferon-alpha2b on the murine Renca renal cell carcinoma cell line in vitro
      and in vivo.
AB  - Novel therapeutic strategies to improve clinical efficacy in patients with renal
      cell carcinoma (RCC) are required. The possibility of combination therapy with
      Lycium barbarum polysaccharides (LBP) and recombinant interferon (IFN)-alpha2b
      remains to be elucidated in RCC. The present study investigated the putative
      synergistic immunotherapeutic roles of LBP and IFN-alpha2b against RCC in vitro
      and in vivo. The mouse RCC cell line, Renca, was used for in vitro experiments.
      Treatment of the cells with a combination of LBP and IFN-alpha2b markedly
      inhibited cell proliferation, retarded cell cycle growth and promoted apoptosis
      in the Renca cells. Western blot analysis revealed that LBP and IFN-alpha2b
      synergistically downregulated the expression levels of cyclin D1, c-Myc and Bcl
      2, and upregulated the expression of the antiapoptotic protein, Bax. Myeloid
      derived suppressor cells (MDSCs) were markedly upregulated during tumour
      progression and promoted tumour growth by inhibiting the T-cell-mediated immune
      response. In vivo, a marked reduction in the MDSC ratio and tumour volume was
      observed in a group receiving combined treatment with LBP and IFN-alpha2b in a
      xenograft tumour model. In conclusion, the present study suggested that the
      combination of LBP and IFN-alpha2b is likely to be more effective in treating
      murine RCC compared with the less pronounced immunotherapeutic effects of
      administering LBP or IFN-alpha2b alone.

PMID- 26300074
TI  - Two-gene mutation in a single patient: Biochemical and functional analysis for a
      correct interpretation of exome results.
AB  - Next-generation sequencing (NGS) has generated a large amount of sequence data
      with the requirement of frequent critical revisions of reported mutations. This
      innovative tool has proved to be effective in detecting pathogenic mutations;
      however, it requires a certain degree of experience to identify incidental
      findings. In the present study, whole exome sequencing analysis was performed for
      the molecular diagnosis and correct genotype/phenotype correlation between
      parents and a patient presenting with an atypical phenotype. In addition,
      mevalonic acid quantification and frequency analysis of detected variants in
      public databases and X-chromosome inactivation (XCI) studies on the patient's
      mother were performed. V377I as well as the S135L mutations were identified on
      the mevalonate kinase deficiency gene and the levels of mevalonic acid in the
      patient were 5,496 ug/ml. A D59G variation, reported in ESP6500 in two healthy
      individuals, was found on the Martin Probst syndrome gene (RAB40AL). Based on XCI
      studies on the patient's mother, it is likely that RAB40AL escapes XCI, while
      still remaining balanced. In conclusion, the results of the present study
      indicated that the Martin Probst syndrome is an X-linked condition, which is
      probably not caused by RAB40AL mutations. Although NGS is a powerful tool to
      identify pathogenic mutations, the analysis of genetic data requires expert
      critical revision of all detected variants.

PMID- 26300075
TI  - Study of spin-ordering and spin-reorientation transitions in hexagonal manganites
      through Raman spectroscopy.
AB  - Spin-wave (magnon) scattering, when clearly observed by Raman spectroscopy, can
      be simple and powerful for studying magnetic phase transitions. In this paper, we
      present how to observe magnon scattering clearly by Raman spectroscopy, then
      apply the Raman method to study spin-ordering and spin-reorientation transitions
      of hexagonal manganite single crystal and thin films and compare directly with
      the results of magnetization measurements. Our results show that by choosing
      strong resonance condition and appropriate polarization configuration, magnon
      scattering can be clearly observed, and the temperature dependence of magnon
      scattering can be simple and powerful quantity for investigating spin-ordering as
      well as spin-reorientation transitions. Especially, the Raman method would be
      very helpful for investigating the weak spin-reorientation transitions by
      selectively probing the magnons in the Mn(3+) sublattices, while leaving out the
      strong effects of paramagnetic moments of the rare earth ions. 

PMID- 26300076
TI  - Demonstration of a high-intensity neutron source based on a liquid-lithium target
      for Accelerator based Boron Neutron Capture Therapy.
AB  - A free surface liquid-lithium jet target is operating routinely at Soreq Applied
      Research Accelerator Facility (SARAF), bombarded with a ~1.91 MeV, ~1.2 mA
      continuous-wave narrow proton beam. The experiments demonstrate the liquid
      lithium target (LiLiT) capability to constitute an intense source of epithermal
      neutrons, for Accelerator based Boron Neutron Capture Therapy (BNCT). The target
      dissipates extremely high ion beam power densities (>3 kW/cm(2), >0.5 MW/cm(3))
      for long periods of time, while maintaining stable conditions and localized
      residual activity. LiLiT generates ~3*10(10) n/s, which is more than one order of
      magnitude larger than conventional (7)Li(p,n)-based near threshold neutron
      sources. A shield and moderator assembly for BNCT, with LiLiT irradiated with
      protons at 1.91 MeV, was designed based on Monte Carlo (MCNP) simulations of BNCT
      doses produced in a phantom. According to these simulations it was found that a
      ~15 mA near threshold proton current will apply the therapeutic doses in ~1h
      treatment duration. According to our present results, such high current beams can
      be dissipated in a liquid-lithium target, hence the target design is readily
      applicable for accelerator-based BNCT.

PMID- 26300080
TI  - A new spin on blood glucose testing.

PMID- 26300077
TI  - Leisure-Time Physical Inactivity Associated with Vascular Depression or Apathy in
      Community-Dwelling Elderly Subjects: The Sefuri Study.
AB  - BACKGROUND: Although physical inactivity is a major public health problem, the
      causative factors for physical inactivity per se are poorly understood. To
      address this issue, we investigated the relationship between deep white matter
      lesions (DWMLs) on magnetic resonance imaging, apathy, and physical activities
      using structural equation modeling (SEM). METHODS: We examined 317 community
      dwelling elderly subjects (137 men and 180 women with a mean age of 64.5 years)
      without dementia or clinically apparent depression. Physical activity was
      assessed with a questionnaire consisting of 3 components (leisure-time, work, and
      sport activities). RESULTS: The mean score from the apathy scale (a visual
      analogue version of Starkstein's apathy scale) of the Grades 2-3 DWML group was
      420 (95% confidence interval [CI] 379-461), which was lower (more apathetic) than
      the Grade 0 DWML group score of 478 (95% CI 463-492) after adjustment for
      education as a covariate. SEM showed that the direct paths from DWMLs or
      education to apathy were significant, and the direct path from apathy to leisure
      time activity was highly significant (beta = .25, P < .001). The degree of
      apathetic behavior was negatively associated with sport activity in female
      subjects and positively associated with TV watching in male subjects.
      CONCLUSIONS: The results of the study show that DWMLs are one of the major
      factors that cause apathetic behavior and that apathy has significant negative
      effects on leisure-time physical activity in community-dwelling elderly subjects.
      Even a minor level of apathy without major depression would have a significant
      impact on activities of daily living and quality of life.

PMID- 26300081
TI  - Tapeworms temper immune reactions.

PMID- 26300078
TI  - Effects of calcium oxide treatment at varying moisture concentrations on the
      chemical composition, in situ degradability, in vitro digestibility and gas
      production kinetics of anaerobically stored corn stover.
AB  - The objective of this study was to determine the optimum conditions for calcium
      oxide (CaO) treatment of anaerobically stored corn stover by in situ and in vitro
      methods. Four ruminally cannulated, non-lactating, non-pregnant Holstein cows
      were used to determine the in situ effective degradabilities of dry matter
      (ISDMD), organic matter (ISOMD), neutral detergent fibre (ISNDFD), in vitro
      organic matter disappearance (IVOMD) and gas production in 72 h (GP72h ) of corn
      stover. A completely randomized design involving a 3 * 3 factorial arrangement
      was adopted. Ground corn stover was treated with different levels of CaO (3%, 5%
      and 7% of dry stover) at varying moisture contents (40%, 50% and 60%) and stored
      under anaerobic conditions for 15 days before analysis. Compared with untreated
      corn stover, the CaO-treated stover had increased ash and calcium (Ca) contents
      but decreased aNDF and OM contents. The moisture content, CaO level and their
      interaction affected (p < 0.01) the content of aNDF, ash and OM, and the ratio of
      aNDF/OM. The greatest ISDMD, ISOMD and ISNDFD were observed when stover was
      treated with 7% CaO and 60% moisture, while no differences (p > 0.01) in these in
      situ degradability parameters were observed between the stover treated with 5%
      CaO at 60% moisture content and those treated with 7% CaO at 60% moisture
      content. Corn stover treated with 5% CaO at 50% moisture had the maximum IVOMD
      and GP72 h among the treatments, and there was no difference (p > 0.01) between
      50% and 60% moisture. Results from this study suggested that 5% CaO applied at
      60% moisture could be an effective and economical treatment combination. 

PMID- 26300083
TI  - Variation aids virulent invaders.

PMID- 26300084
TI  - 'Unlearning' addiction.

PMID- 26300086
TI  - A reliable ruminate for research.

PMID- 26300087
TI  - Response to Protocol Review Scenario: Compliant but not complete.

PMID- 26300088
TI  - Expediting assignment of protocol reviewers.

PMID- 26300089
TI  - Response to Protocol Review Scenario: A word from OLAW and USDA.

PMID- 26300090
TI  - Response to Protocol Review Scenario: Overly cautious IACUC manager.

PMID- 26300091
TI  - Response to Protocol Review Scenario: Laws should reflect reality.

PMID- 26300092
TI  - Primate wellness exams.
AB  - Non-human primates (NHPs) continue to serve unique animal research needs. Decades
      of biomedical research have focused on humane restraint and social and
      environmental enrichment programs necessary to support NHPs, but the housing and
      care of NHPs remain challenging because of the occupational safety hazards faced
      by employees who are tasked with the care and use of these valuable animals. Key
      to obtaining reliable results, providing humane care and ensuring occupational
      safety when working with NHPs is a sound annual wellness examination. Clinical
      techniques in veterinary medicine have improved in parallel with efforts to
      improve psychological well-being, so the timing is opportune to update clinical
      techniques inside the primate facility. 

PMID- 26300093
TI  - Short course on experimental design.

PMID- 26300094
TI  - Productivity of superovulated C57BL/6J oocyte donors at different ages.
AB  - Superovulation is often used to increase the number of oocytes that can be
      collected from donor females for in vitro fertilization. Donor age can affect the
      quantity and quality of oocytes produced during superovulation, and in some
      strains of mice juvenile females are optimal donors. The authors reviewed donor
      and oocyte records from a breeding program to evaluate how donor age affects the
      number and fertilization efficiency of oocytes collected from C57BL/6J mice.
      Generally fewer oocytes per donor were collected from females aged > 32 d than
      from females aged 21-32 d. Fertilization efficiency of oocytes generally declined
      with donor age when oocytes were fertilized with fresh or with stored sperm.
      These findings suggest that the use of younger C57BL/6J donors, instead of older
      donors, can reduce the number of donors needed for IVF procedures. 

PMID- 26300095
TI  - Management methods to improve the welfare of horses used in research.
AB  - Horses and ponies are used for experimental research in a variety of fields, but
      there is little published scientific literature that describes current or
      evidence-based recommendations for keeping and managing these species for
      research purposes. Equine species require particular environmental conditions and
      allowances to accommodate their behavior and physiology. Here the authors review
      studies and common practices for ambient facility conditions; provision of
      bedding, food and water; opportunities for exercise and environmental enrichment;
      allocation of facility spaces and resources; and design and management of
      different stabling systems for horses and ponies in research. Careful
      consideration of these factors can help to improve the welfare of equine subjects
      in research and to ensure high-quality experimental data. 

PMID- 26300096
TI  - Training tips for animal tattooing.

PMID- 26300097
TI  - Exceptions can be costly.

PMID- 26300098
TI  - From board sports to board exams.

PMID- 26300099
TI  - Reflection on observation: A qualitative study using practice development methods
      to explore the experience of being a hand hygiene auditor in Australia.
AB  - BACKGROUND: Within the Australian public health care system, an observation model
      is used to assess hand hygiene practice in health care workers, culminating in a
      publicly available healthcare service performance indicator. The intent of this
      study was for the results to inform the development of a strategy to support
      individual auditors and local sustainability of the hand hygiene auditing
      program. METHOD: This qualitative study used a values clarification tool to gain
      an understanding of the experiences of hand hygiene auditors. The methodology
      involved qualitative interpretation of focus group discussions to identify the
      enablers and barriers to successful performance of the auditors' role. RESULTS:
      Twenty-five participants identified congruous themes of the need for peer and
      managerial support, improved communication and feedback, and consideration for
      succession planning. There was consistency in the participants' most frequently
      identified significant barriers in undertaking the role. CONCLUSION: Hand hygiene
      auditors take pride in their role and work toward the goal of reducing health
      care-associated infections by having a part to play in improving hand hygiene
      practices of all staff members. Important themes, barriers, and enablers were
      identified in this study. This research will be of interest nationally and
      globally, considering the dearth of published information on the experience of
      hand hygiene auditors. This study provides evidence of the need to support
      individual hand hygiene auditors.

PMID- 26300100
TI  - Risk factors for surgical site infections after neurosurgery: A focus on the
      postoperative period.
AB  - BACKGROUND: Surgical site infection (SSI) after neurosurgery has potentially
      devastating consequences. METHODS: A prospective cohort study was conducted over
      a period of 24 months in a university center. All adult patients undergoing
      neurosurgical procedures, with exception of open skull fractures, were included.
      Multivariate logistic regression analysis was used to identify independent risk
      factors. RESULTS: We included 949 patients. Among them, 43 were diagnosed with
      SSI (4.5%). A significant reduction in postneurosurgical SSI from 5.8% in 2009 to
      3.0% in 2010 (P = .04) was observed. During that period, an active surveillance
      with regular feedback was established. The most common microorganisms isolated
      from SSI were Staphylococcus aureus (23%), Enterobacteriaceae (21%), and
      Propionibacterium acnes (12%). We identified the following independent risk
      factors for SSI postcranial surgery: intensive care unit (ICU) length of stay >=7
      days (odds ratio [OR] = 6.1; 95% confidence interval [CI], 1.7-21.7), duration of
      drainage >=3 days (OR = 3.3; 95% CI, 1.1-11), and cerebrospinal fluid leakage (OR
      = 5.6; 95% CI, 1.1-30). For SSIs postspinal surgery, we identified the following:
      ICU length of stay >=7 days (OR = 7.2; 95% CI, 1.6-32.1), coinfection (OR = 9.9;
      95% CI, 2.2-43.4), and duration of drainage >=3 days (OR = 5.7; 95% CI, 1.5-22).
      CONCLUSION: Active surveillance with regular feedback proved effective in
      reducing SSI rates. The postoperative period is associated with overlooked risk
      factors for neurosurgical SSI. Infection control measures targeting this period
      are therefore promising.

PMID- 26300101
TI  - Are identity badges and lanyards in pediatrics potentially contaminated with
      viral pathogens?
AB  - Identity (ID) badges and lanyards worn by pediatric health care workers (HCWs)
      have been shown to be potential vectors of nosocomial bacterial infections. This
      cross-sectional study determined the contamination of ID badges and lanyards worn
      by pediatric HCWs with common respiratory and gastrointestinal viruses. The
      results showed that ID badges and lanyards are not significantly contaminated
      with common respiratory or gastrointestinal viruses and are unlikely to be a
      significant vector for nosocomial infection. 

PMID- 26300102
TI  - Use of statins and the risk of acute pancreatitis: a population-based case
      control study.
AB  - PURPOSE: The aim of this research was to examine the association between statin
      use and the risk of acute pancreatitis. METHODS: This register-based case-control
      study with incidence density sampling was based on 4376 patients hospitalized in
      2008-2010 for acute pancreatitis and 19 859 randomly selected age and sex-matched
      controls from the adult population of Finland. The relationship between statin
      use from 1 January 2004 to the index date and the relative incidence rate of
      acute pancreatitis was modelled by conditional logistic regression. The rate
      ratios were adjusted for comorbidities. RESULTS: A total of 826 (19%) cases and
      2589 (13%) controls had been exposed to statins. Statin use was associated with
      an increased incidence rate of acute pancreatitis (odds ratio (OR) 1.25, 95%
      confidence interval (CI) 1.13-1.39). This increase was seen especially during the
      first year of use both among current (OR 1.37, 95% CI 0.94-2.00 for at most 3
      months of use and OR 1.32, 95% CI 1.07-1.63 for 4-12 months of use) and former
      users (OR 1.64, 95% CI 1.33-2.03). The overall association remained when
      restricting analyses to participants with current use only, or with no history of
      gallstone or alcohol-related diseases, or with no comorbidities or medicines
      other than statins. CONCLUSIONS: Statin use seems to be associated with an
      increased risk of acute pancreatitis. The association is more apparent during the
      first year of statin use and among former users.

PMID- 26300103
TI  - [Practical issues in the management of tuberculosis disease].
AB  - INTRODUCTION: Tuberculosis disease warrants standard therapeutic management as
      detailed in a guide published by the High Authority for Health (HAS) following
      the publication of the Public Health Law in 2004. METHODS: The medical services
      of the regime social des independants (RSI) carried out a national survey by
      targeting patients who, in 2011, were reimbursed for tuberculosis treatment or
      were admitted for long-term tuberculosis disease. Their physicians were contacted
      to detail the care pathway and treatment they had received. RESULTS: A total of
      148 tuberculosis disease patients were enrolled, of whom 71.6% had respiratory
      localization of their disease. The diagnosis was made in healthcare institutions
      in 84.5% of cases. Standard treatment (phases 1 and 2) was used in 30.1% of
      cases. The recommended quadruple therapy was given in 55.2% of treatments in
      phase 1 and in accordance with the time recommended in 62.9% of cases. Phase 2
      was the recommended two drugs combination therapy 80.4% of the time with the
      treatment duration respected in 51.0% of treatments. The difference from standard
      treatment was explained by the detection of health or social events in only 39.0%
      of cases. CONCLUSION: This survey allows us to highlight a relative lack of
      knowledge of standard treatment as recommended by the HAS.

PMID- 26300104
TI  - Peri-implant failure in dual plating of the distal humerus-A biomechanical
      analysis with regard to screw and plate positioning.
AB  - PURPOSE: The aim of this biomechanical study was to analyse the influence of
      plate and screw positioning on peri-implant failure in dual plate osteosynthesis.
      We hypothesized that screw positioning rather than plate configuration influences
      the risk of peri-implant fractures. METHODS: Twenty macerated humerus specimens
      were available. 5 groups of 4 were built according to specimen size. Locking dual
      plates (Medartis, Switzerland) were randomly applied to the distal humerus of the
      specimens in 4 types of configuration: Bending forces were applied using a
      universal testing machine until peri-implant fracture occurred. RESULTS: Mean
      failure loads for respective configuration types were as follows: P1: 428.7 (+/
      84.2) N, A1: 410.0 (+/-54.7) N, A0: 297.8 (+/-48.3) N, P0: 261.0 (+/-65.0) N.
      Configurations with positioning of the most proximal screws at different levels
      (P1, A1) reached significantly higher failure loads when compared to screw
      placement at the same level (P0, A0) (0.01<=p<=0.03). Altering the plate
      configuration did not significantly influence failure loads (0.34<=p<=0.58).
      CONCLUSIONS: The results of this study suggest that placement of the most
      proximal screws rather than the configuration of the plates is critical regarding
      the predetermined risk of peri-implant failure in dual plate osteosynthesis of
      the distal humerus. Varying levels of the outermost screws of corresponding
      double plates seem to be crucial to avoid complications related to the
      osteosynthesis.

PMID- 26300105
TI  - Simultaneous quantification of Escherichia coli O157:H7 and Shigella boydii using
      a visual-antibody-macroarray.
AB  - Being high throughput, rapid, automated, economical, convenient to operate and
      highly sensitive, protein arrays have been widely used in the analysis of tumor
      markers and veterinary drug residues. Pathogenic microbes also can be detected
      qualitatively by DNA array or protein array; however, their high throughput
      detection and quantification remains a big obstacle. To evaluate the potentiality
      of protein arrays for multiple quantitative detection of microorganisms with
      naked eye examination without the help of any equipment, here we developed a
      visual-antibody-macroarray (VAMA) aiming at rapid and simultaneous quantification
      of Escherichia coli O157:H7 and Shigella boydii. The results show that this VAMA
      is highly specific and is able to distinguish mixed Escherichia coli O157:H7 and
      Shigella boydii synchronously. The detection limits are equivalent to 3.4 * 10(5)
      CFU mL(-1) and 3.2 * 10(5) CFU mL(-1), respectively, which conform to the results
      of plate counting and ELISA. Importantly, the examination can be solely performed
      with the naked eye. Therefore, we provide an easy, reliable and rapid method for
      quantitative analysis of microorganisms. 

PMID- 26300106
TI  - In memoriam David C. Seldin, MD, PhD.

PMID- 26300107
TI  - Wildlife sequences of islet amyloid polypeptide (IAPP) identify critical species
      variants for fibrillization.
AB  - Amyloid can be detected in the islets of Langerhans in a majority of type 2
      diabetic patients. These deposits have been associated with beta-cell death,
      thereby furthering diabetes progression. Islet amyloid polypeptide (IAPP)
      amyloidogenicity is quite variable among animal species, and studying this
      variability could further our understanding of the mechanisms involved in the
      aggregation process. Thus, the general aim of this study was to identify IAPP
      isoforms in different animal species and characterize their propensity to form
      fibrillar aggregates. A library of 23 peptides (fragment 8-32) was designed to
      study the amyloid formation using in silico analysis and in vitro assays. Amyloid
      formation was impeded when the NFLVH motif found in segment 8-20 was substituted
      by DFLGR or KFLIR segments. A 29P, 14K and 18R substitution were often present in
      non-amyloidogenic sequences. Non-amyloidogenic sequences were obtained from
      Leontopithecus rosalia, Tursiops truncatus and Vicugna pacos. Fragment peptides
      from 34 species were amyloidogenic. To conclude, this project advances our
      knowledge on the comparative pathogenesis of amyloidosis in type II diabetes. It
      is conceivable that the additional information gained may help point towards new
      therapeutic strategies for diabetes patients. 

PMID- 26300108
TI  - The rate and significance of type 1/type 2 serum amyloid A protein gene
      polymorphisms in patients with ankylosing spondylitis and amyloidosis.
AB  - A relationship between the presence of amyloidosis and SAA1 genotype has been
      shown in recent studies of (principally) familial Mediterranean fever patients.
      We found that the SAA1 rs12218 polymorphism was significantly more prevalent in
      ankylosing spondylitis patients with amyloidosis. 

PMID- 26300109
TI  - Stress-induced sensitization: the hypothalamic-pituitary-adrenal axis and beyond.
AB  - Exposure to certain acute and chronic stressors results in an immediate
      behavioral and physiological response to the situation followed by a period of
      days when cross-sensitization to further novel stressors is observed. Cross
      sensitization affects to different behavioral and physiological systems, more
      particularly to the hypothalamus-pituitary-adrenal (HPA) axis. It appears that
      the nature of the initial (triggering) stressor plays a major role, HPA cross
      sensitization being more widely observed with systemic or high-intensity
      emotional stressors. Less important appears to be the nature of the novel
      (challenging) stressor, although HPA cross-sensitization is better observed with
      short duration (5-15 min) challenging stressors. In some studies with acute
      immune stressors, HPA sensitization appears to develop over time (incubation),
      but most results indicate a strong initial sensitization that progressively
      declines over the days. Sensitization can affect other physiological system (i.e.
      plasma catecholamines, brain monoamines), but it is not a general phenomenon.
      When studied concurrently, behavioral sensitization appears to persist longer
      than that of the HPA axis, a finding of interest regarding long-term consequences
      of traumatic stress. In many cases, behavioral and physiological consequences of
      prior stress can only be observed following imposition of a new stressor,
      suggesting long-term latent effects of the initial exposure.

PMID- 26300110
TI  - First comprehensive assessment of the burden of consultations for influenza in
      the USA.

PMID- 26300112
TI  - Addition of Angiotensin-Converting Enzyme Inhibitors to Beta-Blockers Does Not
      Have a Distinct Effect on Hispanics Compared With African Americans and Whites
      With Heart Failure and Reduced Ejection Fraction.

PMID- 26300113
TI  - Towards an understanding of the singlet-triplet splittings in conjugated
      hydrocarbons: azulene investigated by anion photoelectron spectroscopy and
      theoretical calculations.
AB  - In this work, the relative energetics and the character of singlet and triplet
      states of azulene have been investigated by photodetachment photoelectron
      spectroscopy (PD-PES) at radical anions and high-level multi-reference
      configuration interaction (MRCI) theory. Anion-to neutral electronic transition
      energies and singlet-triplet splittings have been measured directly by PD-PES and
      have been assigned with the help of the calculated transition energies and
      simulated Franck-Condon spectra. The good agreement between experiment and theory
      justifies the conclusion that the geometrical structure of the azulene radical
      anion lies in-between the geometries of the neutral ground state and those of the
      excited states. By the detour via the radical anion, we observed the T1 and S1
      origins of azulene in the same spectrum for the first time and were able to
      resolve their small splitting of 49 meV. This small singlet-triplet splitting was
      explained before by the small overlap of the electron densities in the highest
      occupied and lowest unoccupied orbital. In this work, this concept is generalized
      and applied to the higher excited electronic states of azulene as well as to its
      alternant aromatic isomer naphthalene. The results confirm our hypothesis that
      the energetic splittings of corresponding singlet-triplet pairs can be related to
      the degree to which the electron density distributions of the involved half
      occupied orbitals overlap. 

PMID- 26300111
TI  - Incidence of medically attended influenza during pandemic and post-pandemic
      seasons through the Influenza Incidence Surveillance Project, 2009-13.
AB  - BACKGROUND: Since the introduction of pandemic influenza A (H1N1) to the USA in
      2009, the Influenza Incidence Surveillance Project has monitored the burden of
      influenza in the outpatient setting through population-based surveillance.
      METHODS: From Oct 1, 2009, to July 31, 2013, outpatient clinics representing 13
      health jurisdictions in the USA reported counts of influenza-like illness (fever
      including cough or sore throat) and all patient visits by age. During four years,
      staff at 104 unique clinics (range 35-64 per year) with a combined median
      population of 368,559 (IQR 352,595-428,286) attended 35,663 patients with
      influenza-like illness and collected 13,925 respiratory specimens. Clinical data
      and a respiratory specimen for influenza testing by RT-PCR were collected from
      the first ten patients presenting with influenza-like illness each week. We
      calculated the incidence of visits for influenza-like illness using the size of
      the patient population, and the incidence attributable to influenza was
      extrapolated from the proportion of patients with positive tests each week.
      FINDINGS: The site-median peak percentage of specimens positive for influenza
      ranged from 58.3% to 77.8%. Children aged 2 to 17 years had the highest incidence
      of influenza-associated visits (range 4.2-28.0 per 1000 people by year), and
      adults older than 65 years had the lowest (range 0.5-3.5 per 1000 population).
      Influenza A H3N2, pandemic H1N1, and influenza B equally co-circulated in the
      first post-pandemic season, whereas H3N2 predominated for the next two seasons.
      Of patients for whom data was available, influenza vaccination was reported in
      3289 (28.7%) of 11,459 patients with influenza-like illness, and antivirals were
      prescribed to 1644 (13.8%) of 11,953 patients. INTERPRETATION: Influenza
      incidence varied with age groups and by season after the pandemic of 2009
      influenza A H1N1. High levels of influenza virus circulation, especially in young
      children, emphasise the need for additional efforts to increase the uptake of
      influenza vaccines and antivirals. FUNDING: US Centers for Disease Control and
      Prevention.

PMID- 26300114
TI  - Effects of resting modes on human lumbar spines with different levels of
      degenerated intervertebral discs: a finite element investigation.
AB  - BACKGROUND: The negative effect of long-term working load on lumbar is widely
      known. However, insertion of different resting modes on long-term working load,
      and its effects on the lumbar spine is rarely studied. The purpose of this study
      was to investigate the biomechanical responses of lumbar spine with different
      levels of degenerated intervertebral discs under different working-resting modes.
      METHODS: Four poroelastic finite element models of lumbar spinal segments L2-L3
      with different grades of disc degeneration were developed. Four different loading
      conditions represented four different resting frequencies, namely, no rest, one
      time long rest, three-time moderate rests, and five-time short rests, on the
      condition that the total resting time was the same except in the no rest mode.
      Loading amplitudes of diurnal activities included 100 N, 300 N, and 500 N.
      RESULTS: With increasing resting frequency, the axial effective stress and fluid
      loss decreased, whereas the pore pressure and radial displacement increased.
      Under different resting frequencies, the changing rate of each biomechanical
      parameter was different. CONCLUSIONS: Under a situation of fixed total resting
      time, high resting frequency was advisable. If sufficient resting frequency was
      unavailable for healthy people as well as patients with mildly and moderately
      degenerated intervertebral discs, they could similarly benefit from relatively
      less resting frequencies. However, one-time rest will not be useful in cases
      where intervertebral discs were seriously degenerated. Reasonable working-resting
      modes for different degrees of disc degeneration, which could assist patients
      achieve a better restoration, were provided in this study.

PMID- 26300115
TI  - HLA-A-B-C-DRB1-DQB1 phased haplotypes in 124 Nigerian families indicate extreme
      HLA diversity and low linkage disequilibrium in Central-West Africa.
AB  - The simultaneous typing of five-HLA loci at high resolution and the availability
      of pedigree data allowed us to characterize extended five-locus phased haplotypes
      in 124 Nigerian families and to compare the observed frequencies with those
      expected by an expectation-maximization algorithm for unphased data. Despite the
      occurrence of some frequent alleles at each locus (e.g. B*53:01, which is assumed
      to protect against Plasmodium falciparum), as many as 82% of the sampled
      individuals carry two unique five-locus haplotypes and only three extended
      haplotypes with frequency above 1% exhibit significant linkage disequilibrium.
      Although preliminary, these results reveal an extreme level of HLA diversity in
      the Nigerian population, which reflects both its multi-ethnic composition and the
      very ancient demographic history of African populations. 

PMID- 26300116
TI  - Bioaccumulation and biosorption of Cd(2+) and Zn(2+) by bacteria isolated from a
      zinc mine in Thailand.
AB  - The three bacteria, Tsukamurella paurometabola A155, Pseudomonas aeruginosa B237,
      and Cupriavidus taiwanensis E324, were isolated from soils collected from a zinc
      mine in Tak Province, Thailand. Among these bacteria, P. aeruginosa B237 and C.
      taiwanensis E324 were tolerant of both cadmium and zinc, while T. paurometabola
      A155 was highly tolerant of zinc only. Bioaccumulation experiment revealed that
      Cd(2+) and Zn(2+) were mainly adsorbed on the cell walls of these bacteria rather
      than accumulated inside the cells. During Cd(2+) and Zn(2+) biosorption, P.
      aeruginosa B237 and T. paurometabola A155 showed the highest removal efficiencies
      for Cd(2+) and Zn(2+), respectively. The maximum biosorption capacities of P.
      aeruginosa B237 and T. paurometabola A155 biomasses for Cd(2+) and Zn(2+)
      biosorptions were 16.89 and 16.75 mg g(-1), respectively, under optimal
      conditions. The experimental data of Cd(2+) and Zn(2+) biosorptions fitted well
      with Langmuir isotherm model, suggesting that Cd(2+) and Zn(2+) adsorptions
      occurred in a monolayer pattern on a homogeneous surface. Furthermore, the pseudo
      second order and pseudo-first order kinetic models best described the biosorption
      kinetics of Cd(2+) and Zn(2+) adsorptions, respectively, suggesting that the
      Cd(2+) and Zn(2+) adsorptions took place mainly by chemisorption (Cd(2+)) and
      physisorption (Zn(2+)).

PMID- 26300117
TI  - Bioaccumulation and tolerance characteristics of a submerged plant (Ceratophyllum
      demersum L.) exposed to toxic metal lead.
AB  - A hydroponic study was conducted to investigate the lead bioaccumulation and
      tolerance characteristics of Ceratophyllum demersum L. exposed to various lead
      concentrations (5-80 MUM) for 7, 14 or 21 days. Lead accumulation increased with
      increasing concentrations of metal in the solution, to a maximum accumulation of
      4016.4 mg kg(-1) dw. Unexpectedly, the release of accumulated lead from the
      plants into solution was observed for all experimental groups except those
      exposed to 5 MUM. Both the biomass and protein content of the plants responded
      significantly to lead stress. Malondialdehyde (MDA) levels increased
      substantially at lead concentrations below 20 MUM, further indicating that this
      metal is toxic to the plants. To reveal the mechanism underlying the defense
      against lead stress, plants were also assayed for the activities of the
      antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and peroxidase
      (POD), as well as other relevant enzymes such as phenylalanine ammonia-lyase
      (PAL) and polyphenol oxidase (PPO). The activities of both SOD and CAT increased
      at lower lead concentrations and with shorter exposure times, followed by a
      decline, but the activities of POD and its isoenzymes continued to increase under
      all conditions. Moreover, increases in the activities of PAL and PPO were
      observed only for the 14-day treatment, and these two enzymes were not sensitive
      to lead concentration. These results suggest that C. demersum exhibits strong
      tolerance within a specific concentration range of lead in solution; according to
      regression analysis, 40 MUM is suggested to be this plant's tolerance threshold
      for lead in water. Furthermore, the malfunction of this tolerance mechanism might
      accelerate the metal-release process. These attributes are likely to be
      beneficial for utilizing C. demersum in phytoremediation applications.

PMID- 26300118
TI  - Earthworm-induced carboxylesterase activity in soil: Assessing the potential for
      detoxification and monitoring organophosphorus pesticides.
AB  - Soil enzyme activities are attracting widespread interest due to its potential
      use in contaminant breakdown, and as indicators of soil deterioration. However,
      given the multiple environmental and methodological factors affecting their
      activity levels, assessment of soil pollution using these biochemical endpoints
      is still complex. Taking advantage of the well-known stimulatory effect of
      earthworms on soil microbes, and their associated enzyme activities, we explored
      some toxicological features of carboxylesterases (CbEs) in soils inoculated with
      Lumbricus terrestris. A microplate-scale spectrophotometric assay using soil
      water suspensions was first optimized, in which kinetic assay parameters (Km,
      Vmax, dilution of soil homogenate, and duration of soil homogenization) were
      established for further CbE determinations. Optimal conditions included a soil-to
      water ratio of 1:50 (w/v), 30-min of shaking, and 2.5mM of substrate
      concentration. As expected, CbE activity increased significantly in soils treated
      with L. terrestris. This bioturbed soil was used for exploring the role of CbE
      activity as a bioscavenger for organophosphorus (OP) pesticides. Soil treated
      with two formulations of chlorpyrifos revealed that CbE activity was a
      significant molecular sink for this pesticide, reducing its impact on soil
      microbial activity as shown by the unchanged dehydrogenase activity. Dose
      dependent curves were adjusted to an exponential kinetic model, and the median
      ecological dose (ED50) for both pesticide formulations was calculated. ED50
      values decreased as the time of pesticide exposure increased (14 d-ED50s=20.4
      26.7 mg kg(-1), and 28 d-ED50s=1.8-2.3 mg kg(-1)), which suggested that
      chlorpyrifos was progressively transformed into its highly toxic metabolite
      chlorpyrifos-oxon, but simultaneously was inactivated by CbEs. These results were
      confirmed by in vitro assays that showed chlorpyrifos-oxon was a more potent CbE
      inhibitor (IC50=35.5-4.67 nM) than chlorpyrifos (0.41-0.84 MUM). The results
      showed that earthworm-induced CbE activity is an efficient bioscavengers for OP
      pesticides, acting as a soil safeguarding system. Moreover, the simple dose
      response curves against OP exposure suggest that this enzyme--combined with other
      enzyme activities (e.g., dehydrogenase)--may be a suitable biomarker of pesticide
      exposure.

PMID- 26300119
TI  - Changes in head dimensions in children from Northern Kashubia (Pomerania, Poland)
      during 60 years.
AB  - Over 100 years ago Franz Boas introduced the term 'cranial plasticity' defined as
      a response to various environmental factors. The subject is under continuous
      debate. Some researchers have concluded that cephalic growth is responsible to
      environmental change meanwhile other have found that cephalic proportion are
      highly heritable and do not respond readily to environmental insults. While
      secular trend in growth is commonly observed, head dimensions vary significantly
      not only between different regions of the world but also in those regions
      themselves. Adam Wrzosek and Michal Cwirko-Godycki initiated studies of Kashubian
      children as early as in 1925 and continued them into 1936. Throughout those 11
      years they accumulated measurement data regarding body height and craniometric
      features. The research included boys and girls from 18 localities. Sixty years
      later, anthropometric measurements were conducted on primary school children from
      nine of the original localities. The aim of our study was to determine the
      direction of changes in head dimensions and corresponding indices in rural
      children from the Kashubia region examined 60 years after Cwirko-Godycki and
      Wrzosek's study emphasizing great socio-economic status improvement. All children
      that were examined by us in 1997 are significantly taller (by between 5.18 cm and
      14.74 cm) than their peers 60 years ago, their heads are longer (by between 2.69
      mm and 10.41 mm), they have broader foreheads (by 3.79 - 7.24 mm), wider faces
      (by 4.68 - 8.09 mm) and mandibles (by 5.04 - 7.40 mm), larger head circumferences
      (by 0.64 - 2.22 cm) and larger total face heights (by 2.15 - 8.13 mm). The effect
      persists in all age groups (from 7 to 14 years old). All the noted differences
      are statistically significant by p < 0.05. The smallest differences were observed
      in head breadth (between 0.62 and 3.5 mm), with statistical significance only
      reached in 9-year-old girls, and 11- and 14-year-old boys. Since migration in
      Kashubian villages was minimal in the period in question and the mating radius
      for couples living there was small, it can be assumed that the chance of
      introducing 'new' genes into the population was low. We thus gravitate towards
      environmental factors being the major contributors to the observed changes,
      doubtlessly to do with an improvement in socio-economic status. 

PMID- 26300120
TI  - Isolation and Biosynthesis of an Azoxyalkene Compound Produced by a Multiple Gene
      Disruptant of Streptomyces rochei.
AB  - Streptomyces rochei 7434AN4 predominantly produces lankacidin and lankamycin
      under normal culture conditions, thus suggesting that other biosynthetic gene
      clusters for secondary metabolites are silent. To identify the silent metabolites
      of 7434AN4, we constructed mutant KA57 with multiple disruptions of the
      transcriptional repressor srrB and the biosynthesis genes for both antibiotics.
      KA57 accumulated a compound (KA57A) with a strong UV absorption at 235 nm, not
      detected in the parent strain or other mutants. Various spectroscopic analyses
      revealed that KA57A is an azoxyalkene compound with the molecular formula C10 H20
      N2 O3 and with the R configuration at C-2. Biosynthesis of KA57A was also studied
      by feeding with labeled acetates, amino acids, and 1-hexylamine. The hexenyl
      moiety (C1'-C6') was derived from fatty acid, whereas the 3-aminobutan-1,2-diol
      moiety (C1-C4) was derived from C-2 of acetate (C1) and serine (C2-C4).
      Incorporation of [1,1-(2) H2 ]-1-hexylamine indicated that C1'-C2'
      dehydrogenation occurs as the final step of biosynthesis.

PMID- 26300121
TI  - Chronic hypoxia and hyperoxia modifies morphology and VEGF concentration of the
      lungs of the developing chicken (Gallus gallus variant domesticus).
AB  - Embryo body and lung wet and dry mass, pulmonary morphometrics and pulmonary VEGF
      concentrations were determined in developing chicken embryos at days 16 and 18
      (D16, D18) in three populations: incubation in normoxia (21% O2) or in chronic
      hypoxia (15% O2) or chronic hyperoxia (30% O2). Lung morphology (including
      parabronchial exchange tissues and parabronchial lumina as a percentage of total
      lung tissue in cross-sectional area, atrial numbers, atrial density) was
      determined from morphometric examination of thin sections using light microscopy.
      VEGF expression was determined with ELISA. Body mass was directly correlated with
      incubation oxygen level, but neither oxygen level affected lung wet mass on
      either D16 or D18. Hypoxia had little or no effect on most measured pulmonary
      morphometric indices in D16 embryos. Hypoxia, however, increased by ~ 65% the
      proportion in cross-section of the total lung occupied by parabronchi on D18.
      Hyperoxia caused few significant changes in pulmonary morphometrics. Pulmonary
      VEGF concentration was decreased by ~ 30% on day 18 compared to D18 in normoxia.
      Hypoxia increased pulmonary VEGF concentration by ~ 35-75% on both D16 and D18
      and, paradoxically, VEGF expression was also similarly increased by hyperoxia on
      only D18. Collectively, these data suggest that pulmonary gross morphological
      development in the chicken embryo, while moderately plastic, is not profoundly
      affected by oxygen incubation level, and that role of VEGF in pulmonary
      development is not yet well understood.

PMID- 26300122
TI  - Identifying the major intermediate species by combining time-resolved X-ray
      solution scattering and X-ray absorption spectroscopy.
AB  - Identifying the intermediate species along a reaction pathway is a first step
      towards a complete understanding of the reaction mechanism, but often this task
      is not trivial. There has been a strong on-going debate: which of the three
      intermediates, the CHI2 radical, the CHI2-I isomer, and the CHI2(+) ion, is the
      dominant intermediate species formed in the photolysis of iodoform (CHI3)?
      Herein, by combining time-resolved X-ray liquidography (TRXL) and time-resolved X
      ray absorption spectroscopy (TR-XAS), we present strong evidence that the CHI2
      radical is dominantly formed from the photolysis of CHI3 in methanol at 267 nm
      within the available time resolution of the techniques (~20 ps for TRXL and ~100
      ps for TR-XAS). The TRXL measurement, conducted using the time-slicing scheme,
      detected no CHI2-I isomer within our signal-to-noise ratio, indicating that, if
      formed, the CHI2-I isomer must be a minor intermediate. The TR-XAS transient
      spectra measured at the iodine L1 and L3 edges support the same conclusion. The
      present work demonstrates that the application of these two complementary time
      resolved X-ray methods to the same system can provide a detailed understanding of
      the reaction mechanism. 

PMID- 26300123
TI  - Leadership and learning.

PMID- 26300124
TI  - Population Variation and Genetic Control of Modular Chromatin Architecture in
      Humans.
AB  - Chromatin state variation at gene regulatory elements is abundant across
      individuals, yet we understand little about the genetic basis of this
      variability. Here, we profiled several histone modifications, the transcription
      factor (TF) PU.1, RNA polymerase II, and gene expression in lymphoblastoid cell
      lines from 47 whole-genome sequenced individuals. We observed that distinct cis
      regulatory elements exhibit coordinated chromatin variation across individuals in
      the form of variable chromatin modules (VCMs) at sub-Mb scale. VCMs were
      associated with thousands of genes and preferentially cluster within chromosomal
      contact domains. We mapped strong proximal and weak, yet more ubiquitous, distal
      acting chromatin quantitative trait loci (cQTL) that frequently explain this
      variation. cQTLs were associated with molecular activity at clusters of cis
      regulatory elements and mapped preferentially within TF-bound regions. We propose
      that local, sequence-independent chromatin variation emerges as a result of
      genetic perturbations in cooperative interactions between cis-regulatory elements
      that are located within the same genomic domain. 

PMID- 26300126
TI  - Targeting of prolamins by RNAi in bread wheat: effectiveness of seven silencing
      fragment combinations for obtaining lines devoid of coeliac disease epitopes from
      highly immunogenic gliadins.
AB  - Gluten proteins are responsible for the viscoelastic properties of wheat flour
      but also for triggering pathologies in susceptible individuals, of which coeliac
      disease (CD) and noncoeliac gluten sensitivity may affect up to 8% of the
      population. The only effective treatment for affected persons is a strict gluten
      free diet. Here, we report the effectiveness of seven plasmid combinations,
      encompassing RNAi fragments from alpha-, gamma-, omega-gliadins, and LMW glutenin
      subunits, for silencing the expression of different prolamin fractions. Silencing
      patterns of transgenic lines were analysed by gel electrophoresis, RP-HPLC and
      mass spectrometry (LC-MS/MS), whereas gluten immunogenicity was assayed by an
      anti-gliadin 33-mer monoclonal antibody (moAb). Plasmid combinations 1 and 2
      downregulated only gamma- and alpha-gliadins, respectively. Four plasmid
      combinations were highly effective in the silencing of omega-gliadins and gamma
      gliadins, and three of these also silenced alpha-gliadins. HMW glutenins were
      upregulated in all but one plasmid combination, while LMW glutenins were
      downregulated in three plasmid combinations. Total protein and starch contents
      were unaffected regardless of the plasmid combination used. Six plasmid
      combinations provided strong reduction in the gluten content as measured by moAb
      and for two combinations, this reduction was higher than 90% in comparison with
      the wild type. CD epitope analysis in peptides identified in LC-MS/MS showed that
      lines from three plasmid combinations were totally devoid of CD epitopes from the
      highly immunogenic alpha- and omega-gliadins. Our findings raise the prospect of
      breeding wheat species with low levels of harmful gluten, and of achieving the
      important goal of developing nontoxic wheat cultivars. 

PMID- 26300127
TI  - The first examples of 1-D organic hybrid lanthanoid thioarsenates based on two
      [As(V)S4](3-) linkage modes.
AB  - A series of new 1-D organic hybrid lanthanoid thioarsenates [Ln(dap)2]2(MU
      eta(1):eta(1):eta(1):eta(1)-AsS4)(MU-eta(1):eta(1)-As(V)S4)]n {Ln = Ce (Ia), Pr
      (Ib), Nd (Ic), and Sm (Id); dap = diaminopropane} have been prepared under
      solvothermal conditions and structurally characterized. Compounds Ia-d contain
      two [As(V)S4](3-) linkage modes, namely MU-eta(1):eta(1):eta(1):eta(1)-As(V)S4
      and MU-eta(1):eta(1)-As(V)S4, which are linked alternately with [Ln(dap)2](3+)
      groups into 1-D neutral chains [Ln(dap)2]2(MU-eta(1):eta(1):eta(1):eta(1)
      As(V)S4)(MU-eta(1):eta(1)-As(V)S4)]n, which represent the first examples of 1-D
      organic hybrid lanthanoid thioarsenates based on two [As(V)S4](3-) linkage modes.
      To learn more about the influence of lanthanide contraction on the formation of
      lanthanoid thioarsenates, five organic hybrid lanthanoid thioarsenates
      [Ln(dap)3As(V)S4] [Ln = Tb (IIa), Dy (IIb), Ho (IIIc), and Er (IIId)] and
      [Er(dien)2As(V)S4] (III, dien = diethylenetriamine) are also provided. Both II
      and III contain neutral lanthanide-centred complexes, where the tetrahedral anion
      [As(V)S4](3-) acts as a chelating ligand to the complex
      [Ln(dap)3](3+)/[Er(dien)2](3+) cation. Their optical properties have been
      characterized by UV-vis spectra, and the density functional theory calculation of
      Ia has been performed. 

PMID- 26300125
TI  - Genetic Control of Chromatin States in Humans Involves Local and Distal
      Chromosomal Interactions.
AB  - Deciphering the impact of genetic variants on gene regulation is fundamental to
      understanding human disease. Although gene regulation often involves long-range
      interactions, it is unknown to what extent non-coding genetic variants influence
      distal molecular phenotypes. Here, we integrate chromatin profiling for three
      histone marks in lymphoblastoid cell lines (LCLs) from 75 sequenced individuals
      with LCL-specific Hi-C and ChIA-PET-based chromatin contact maps to uncover one
      of the largest collections of local and distal histone quantitative trait loci
      (hQTLs). Distal QTLs are enriched within topologically associated domains and
      exhibit largely concordant variation of chromatin state coordinated by proximal
      and distal non-coding genetic variants. Histone QTLs are enriched for common
      variants associated with autoimmune diseases and enable identification of
      putative target genes of disease-associated variants from genome-wide association
      studies. These analyses provide insights into how genetic variation can affect
      human disease phenotypes by coordinated changes in chromatin at interacting
      regulatory elements. 

PMID- 26300128
TI  - Assessment of pelvic floor muscle contraction with palpation, perineometry and
      transperineal ultrasound: a cross-sectional study.
AB  - OBJECTIVE: To study the correlation between palpation, perineometry and
      transperineal ultrasound for assessment of pelvic floor muscle contraction and to
      define a contraction scale for ultrasound measurements. METHODS: This was a cross
      sectional study of 608 women examined with palpation of pelvic floor muscle
      contraction, using the Modified Oxford Scale, and measurement of the vaginal
      squeeze pressure with a vaginal balloon connected to a fiber-optic microtip
      transducer (perineometry). Transperineal ultrasound was used for measurements of
      levator hiatal area and anteroposterior (AP) diameter in the plane of minimal
      hiatal dimensions, at rest and on contraction. The pelvic floor muscle
      contraction was expressed as the percentage difference between values at rest and
      on contraction. Spearman's rank was used to test for correlation between the
      different methods of assessment. RESULTS: Significant correlations were found
      between all assessment methods (P < 0.001). Palpation correlated with
      perineometry (rs = 0.74) and with proportional change in hiatal area (rs = 0.67)
      and AP diameter (rs = 0.69) on ultrasound. Perineometry correlated with
      proportional change in hiatal area (rs = 0.60) and AP diameter (rs = 0.66) on
      ultrasound. We defined a contraction scale based on the proportional change in AP
      diameter. In this population, a change in AP diameter of < 7% corresponded to
      absence of contractions, 7-18% corresponded to weak contractions, 18-35%
      corresponded to normal contractions and > 35% corresponded to strong
      contractions. CONCLUSIONS: We found moderate to strong correlation between
      ultrasound measurements, palpation and perineometry for assessing pelvic floor
      muscle contraction. The proportional change in levator hiatal AP diameter was the
      ultrasound measurement with strongest correlation to palpation and perineometry
      and formed the basis for the contraction scale for ultrasound measurements.
      Copyright (c) 2015 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 26300129
TI  - Erratum: A Novel Audiovisual Brain-Computer Interface and Its Application in
      Awareness Detection.

PMID- 26300130
TI  - Normalizing Intersex: The Transformative Power of Stories.
AB  - The voices of 13 people with intersex traits are shared in this symposium to
      shape dominant medical discourse about intersex bodies and experiences. Four
      commentaries on these narratives by experts from various disciplines are included
      in this issue, with each raising questions that hopefully enhance rather than
      regulate the voices of people with intersex traits. 

PMID- 26300131
TI  - When Doctors Get It Wrong.

PMID- 26300132
TI  - The Secret Inside Me.

PMID- 26300133
TI  - Finding My Compass.

PMID- 26300134
TI  - The Truth in Writing.

PMID- 26300135
TI  - Still I Rise.

PMID- 26300136
TI  - The Son They Never Had.

PMID- 26300137
TI  - A Changed Life: Becoming True to Who I am.

PMID- 26300138
TI  - Standing Up.

PMID- 26300139
TI  - It's a Human Rights Issue!

PMID- 26300140
TI  - Promoting Health and Social Progress by Accepting and Depathologizing Benign
      Intersex Traits.

PMID- 26300141
TI  - Standing at the Intersections: Navigating Life as a Black Intersex Man.

PMID- 26300142
TI  - "Normalizing" Intersex Didn't Feel Normal or Honest to Me.

PMID- 26300143
TI  - Invisible Harm.

PMID- 26300144
TI  - Cris de Coeur and the Moral Imperative to Listen to and Learn from Intersex
      People.
AB  - Intersex people first began to publicly tell their stories in the 1990s. Twenty
      years on, these narratives, scorching in their candor, attest to a continuing
      failure to bear witness to or to acknowledge some of the most painful experiences
      we inflict on one another. More than anecdotes, these narratives provide a first
      person reflection on care and thus represent a type of long-term follow-up that
      is largely absent in clinical literature. Out of respect for their courage, we
      owe these narratives serious consideration. Clinicians who must make daily
      decisions that may alter patients' lives may distance themselves from negative
      outcomes and stories like those told here to avoid professional regret. Honest
      self-appraisal and accepting regret open the door to feeling guilty, devalued and
      ashamed, but experiencing these emotions can be a crucial first step in changing
      clinical practice. 

PMID- 26300145
TI  - Beyond Good Intentions.
AB  - Ethical questions in medicine tend to emphasize the intentions of researchers and
      physicians. Questions concerning harm have more often been addressed in terms of
      legal culpability. This commentary proposes that normalizing interventions for
      atypical sex anatomies, both historical and ongoing, be recognized as a kind of
      medical error, and that attention be focused not simply on prevention, but on
      repair. 

PMID- 26300146
TI  - A Pediatrician's View.
AB  - The experiences of individuals with intersex conditions include considerable
      abuse at the hands of medical personnel. Despite changes in expert opinion about
      full disclosure of the nature of each patient's condition and recommendations to
      defer cosmetic surgical interventions, we do not know how much actual practice
      has changed over several decades. Moreover, discrepancies continue between the
      views of who have these conditions and medical practitioners, especially about
      preventing cancer and retaining gonads for the purpose of providing "natural"
      hormone production. We have insufficient data to resolve these different
      perspectives. 

PMID- 26300147
TI  - Stonewalling Emotion.
AB  - This commentary is an exploration of emotion by a therapist. It focuses on how
      emotion is managed in the stories of growing up and living with atypical sex
      anatomies--how (much) is emotion (not) discussed, and what are the effects of
      forestalling emotive dialogue. Emotion care in the narratives is often sidelined
      in favor of medical doings. Rather than creating a haven to keep normative
      pressures at bay, so as to enable the affected parents, adolecents and adults to
      process their situations, some of the storytellers reveal how medicine has
      concentrated its efforts on the erasure and silencing of their bodily
      differences. The most frequently mentioned emotion management strategy is
      'stonewalling', as some of the affected children and adults were silently left to
      take in what was reflected in the eyes of the large number of people inspecting
      their naked bodies. Emotional suffering continued for many years for some
      individuals. An apology might ease suffering but is rarely bestowed. Learning to
      become more comfortable with emotion may open up more possibilities for helpful
      conversations between care users and providers and within families. Feelings of
      joy became more available to the storytellers who as adults learned to embrace
      their differences and connected with like-minded people.

PMID- 26300148
TI  - African Americans and Hospice Care: A Narrative Analysis.
AB  - Recent studies suggest that terminally ill African Americans' care is generally
      more expensive and of lower quality than that of comparable non-Hispanic white
      patients. Scholars argue that increasing hospice enrollment among African
      Americans will help improve end-of-life care for this population, yet few studies
      have examined the experiences of African American patients and their loved ones
      after accessing hospice care. In this article, we explore how African American
      patients and lay caregivers evaluated their hospice experiences. Drawing from 39
      in-depth interviews with 26 participants, we use a modified version of Bute and
      Jensen's (2011) narrative typology to organize patients' and caregivers' stories
      into three general categories: narratives of satisfaction, narratives of regret,
      and narratives of ambivalence. Building from these categories, we discuss the
      implications of this research for understanding hospice experiences, promoting
      hospice access, and improving end-of-life care for marginalized populations. 

PMID- 26300149
TI  - Conflicting Values: A Case Study in Patient Choice and Caregiver Perspectives.
AB  - Decisions related to births in the "gray zone" of periviability are particularly
      challenging. Despite published management guidelines, clinicians and families
      struggle to negotiate care management plans. Stakeholders must reconcile
      conflicting values in the context of evolving circumstances with a high degree of
      uncertainty within a short time period. Even skilled clinicians may struggle to
      guide the patient in making value-laden decisions without imposing their own
      values. Exploring the experiences of one pregnant woman and her caregivers, this
      case study highlights how bias may undermine caregivers' ability to meet their
      obligation to enhance patient autonomy and the moral distress they may experience
      when a patient's values do not align with their own. Management strategies to
      mitigate the potential impact of bias and related moral distress are identified.
      The authors then describe one management strategy used in this case, facilitated
      ethics consultation, which is focused on thoughtful consideration of the
      patient's perspective. 

PMID- 26300150
TI  - Military Health Care Dilemmas and Genetic Discrimination: A Family's Experience
      with Whole Exome Sequencing.
AB  - Whole-exome sequencing (WES) has increased our ability to analyze large parts of
      the human genome, bringing with it a plethora of ethical, legal, and social
      implications. A topic dominating discussion of WES is identification of
      "secondary findings" (SFs), defined as the identification of risk in an
      asymptomatic individual unrelated to the indication for the test. SFs can have
      considerable psychosocial impact on patients and families, and patients with an
      SF may have concerns regarding genomic privacy and genetic discrimination. The
      Genetic Information Nondiscrimination Act of 2008 (GINA) currently excludes
      protections for members of the military. This may cause concern in military
      members and families regarding genetic discrimination when considering genetic
      testing. In this report, we discuss a case involving a patient and family in
      which a secondary finding was discovered by WES. The family members have careers
      in the U.S. military, and a risk-predisposing condition could negatively affect
      employment. While beneficial medical management changes were made, the
      information placed exceptional stress on the family, who were forced to navigate
      career-sensitive "extra-medical" issues, to consider the impacts of uncovering
      risk-predisposition, and to manage the privacy of their genetic information. We
      highlight how information obtained from WES may collide with these issues and
      emphasize the importance of genetic counseling for anyone undergoing WES. 

PMID- 26300151
TI  - The Enduring Case.
AB  - In clinical ethics an enduring case takes on a life of its own and comes to
      closure over a long period of time. This essay describes the evolution of such a
      case over a 1-year period. The case involves a 90-year old male patient with
      multiple chronic medical conditions who lacked decision-making capacity, was a
      resident of a long-term care facility, and did not have known previously
      expressed wishes regarding medical treatment. The ethics consultation initially
      revolved around this question: What method or process must be employed so that
      medical treatment decisions could be ethically reviewed and could include a
      shared decision-making process for Mr. Smith? This case analysis describes the
      evolution of this case and argues that the good of the patient must remain
      paramount throughout an enduring case. 

PMID- 26300152
TI  - The Surgeon as Stakeholder: Making the Case Not to Operate.
AB  - Surgeons are in a unique position, serving as gatekeepers to the operating room.
      They determine if operations are possible, are indicated, and have a reasonable
      risk-to-benefit profile. When an operation is indicated and the patient is
      amenable to it, the conversation between surgeon and patient is usually
      straightforward. On the other hand, when a patient's co-morbidities substantially
      increase the risk of operative intervention, surgeons often question the utility
      of offering their services. These situations become immensely more difficult when
      patients have the expectation of being offered surgical treatment. This case
      describes the clinical encounter between an endocrine surgeon and an 83-year-old
      woman who has been incidentally found to have adrenal metastasis from melanoma.
      The patient wants an operation that the surgeon is reluctant to offer because of
      her frailty and high operative risk. The case focuses on the ethical dilemma that
      arises when a patient wants an operation that a surgeon does not want to perform.
      I was the resident in the endocrine surgery clinic the day that Ms. M came in.
      Given my background in bioethics, the attending physician told me about the
      patient's history beforehand and asked for advice on how to approach the clinical
      encounter. I then accompanied him into her room to talk with her and her husband.

PMID- 26300153
TI  - Solving the Jigsaw Puzzle.

PMID- 26300154
TI  - Dwelling in the Gaps.

PMID- 26300155
TI  - XY/XO.

PMID- 26300156
TI  - Removing the Mask: Hopeless Isolation to Intersex Advocacy.

PMID- 26300157
TI  - Navigating Intersex Healthcare: My Odyssey.

PMID- 26300158
TI  - Game Change.

PMID- 26300159
TI  - Michael's Story or the Paradox of Normalcy.

PMID- 26300160
TI  - Editors' Note.

PMID- 26300161
TI  - Loculated cardiac hematoma causing hemodynamic compromise after cardiac surgery.
AB  - The authors describe a case of a rare complication occurring after cardiac
      surgery. Three weeks after aortic valve replacement a young male became
      hemodynamically unstable. The echocardiogram showed a large loculated hematoma
      compressing the right atrium. The patient was reoperated and the mass was
      removed. Recovery was complete. 

PMID- 26300162
TI  - Protective effects of edaravone, a free radical scavenger, on lipopolysaccharide
      induced acute kidney injury in a rat model of sepsis.
AB  - PURPOSE: Acute kidney injury (AKI) is a frequent complication of sepsis. The
      present work examined the therapeutic potential of edaravone (EDA), a free
      radical scavenger, for inhibiting sepsis-induced renal injury. METHODS: Saline
      and lipopolysaccharide (LPS) were injected intraperitoneally at a dose of 10
      mg/kg of body weight. EDA, 3-methyl-1-phenyl-pyrazolin-5-one, was administrated
      intravenously at a dose of 3 mg/kg of body weight to male Wistar rats. Wistar
      rats were divided into four groups: treatment with LPS alone, treatment with LPS
      followed by EDA administration, treatment with saline followed by EDA
      administration, and untreated controls. RESULTS: Administration of LPS caused a
      significant increase in BUN and serum creatinine levels with concurrent
      pathological alterations in kidney tissues. EDA treatment relieved all these
      changes. Moreover, EDA reduced LPS-induced elevation of serum TNF-alpha and IL-6
      in rats. Furthermore, EDA could prevent mitochondrial membrane potential loss
      induced by LPS and reverse the changes in mitochondrial antioxidant (such as T
      AOC, SOD, CAT, and GSH) and mitochondrial MDA levels. TUNEL staining of the
      kidney sections and immunoblot analysis on renal cortical lysates showed that EDA
      treatment resulted in reduced number of apoptotic cells, which occurred
      concomitantly with decreased levels of cytochrome c and cleaved caspase 3.
      Following LPS treatment of rat renal tubular cells, mitochondrial fragmentation
      was observed prior to apoptosis, which was inhibited by EDA. CONCLUSIONS: EDA
      prevents LPS-induced AKI not only by reducing the production of inflammatory
      cytokines, but also by attenuating oxidative damage in renal mitochondria,
      mitochondrial fragmentation, and apoptosis of renal cells.

PMID- 26300163
TI  - Evaluation of heat shock proteins for discriminating between latent tuberculosis
      infection and active tuberculosis: A preliminary report.
AB  - The diagnosis of a latent tuberculosis infection (LTBI) is of the utmost concern.
      The available tests, the tuberculin skin test (TST) and the Quantiferon-TB Gold
      test (QFT-G) cannot discriminate between active TB and LTBI. Therefore, the aim
      of the study is to identify new biomarkers that can discriminate between active
      TB and LTBI and can also assess the risk of the individual developing active TB.
      In total, 55 blood samples were collected, of which 10 samples were from the
      active TB infection group, 10 were from the high-risk exposure group, 23 were
      from the low-risk exposure group, and 12 were from healthy controls living in a
      non-TB endemic area. A panel of heat shock proteins (Hsps), including host Hsp25,
      Hsp60, Hsp70, and Hsp90 and Mycobacterium tuberculosis (MTB) Hsp16, were
      evaluated in all of the collected samples using ELISA. The levels of the host
      Hsp(s) (Hsp25, Hsp60, Hsp70 and Hsp90) and MTB Hsp16 were significantly (p<0.05)
      elevated in the active TB group compared to the high-risk exposure group, the low
      risk exposure group and the control group. Notably, the levels of the same panel
      of Hsp(s) were elevated in the high-risk exposure group compared to the low-risk
      exposure group. On follow-up, out of the 10 high-risk exposure participants, 3
      converted into active TB, indicating that this group has the highest risk of
      developing TB. Thus, the evaluated panel of Hsp(s) can discriminate between LTBI
      and active TB. They can also identify individuals who are at the highest risk of
      developing active TB. Because they can be rapidly detected, Hsp(s) have an edge
      over the existing diagnostic tools for LTBI. The evaluation of these proteins
      will be useful in designing better diagnostic methods for LTBI.

PMID- 26300164
TI  - Effect of Several Solutions Including Mineral-encaging Zeolites on the
      Restoration of Cell Motility of Tributyltin-intoxicated Euglena gracilis Z.
AB  - To examine the detoxification effect of mineral-encaged zeolites on cells
      impaired by pollutant-intoxication, we used a bioassay system involving Euglena
      gracilis Z as the model organism and TBTCl as a pollutant. TBTCl exposure causes
      Euglena cells to quickly change shape from a spherical to spindle form, with the
      process being reversible by detoxification. Taking advantage of this
      morphological characteristic, we examined the restoration of motility by water
      containing zeolites encaging different minerals. TBTCl-intoxicated Euglena cells
      were incubated in processed water with different types of mineral-encaging
      zeolites for up to 3 hours. The restoration of motility was evaluated by
      observing the number of motile cells with a video microscope. Remarkable recovery
      was observed in the incubation systems with water containing Fe-, Zn-, and Mn
      encaging zeolites. However, the effect was suppressed when the water species were
      treated with the chelator, Chelex-100((r)). An equivalent concentration of FeCl3
      to that in the Fe-encaging zeolite processed water did not show significant
      restoration effect. 

PMID- 26300165
TI  - Enzymatic Quantification of L-Tartrate in Wines and Grapes by Using the Secondary
      Activity of D-Malate Dehydrogenase.
AB  - L-Tartrate in wines and grapes was enzymatically quantified by using the
      secondary activity of D-malate dehydrogenase (D-MDH). NADH formed by the D-MDH
      reaction was monitored spectrophotometrically. Under the optimal conditions, L
      tartrate (a 1.0 mM sample solution) was fully oxidized by D-MDH in 30 min. A
      linear relationship was obtained between the absorbance difference and the L
      tartrate concentration in the range of a 0.02-1.0 mM sample solution with a
      correlation coefficient of 0.9991. The relative standard deviation from ten
      measurements was 1.71% at the 1.0 mM sample solution level. The proposed method
      was compared with HPLC, and the values determined by both methods were in good
      agreement. 

PMID- 26300166
TI  - Polypeptide Requirement of Multicomponent Monooxygenase DsoABCDEF for Dimethyl
      Sulfide Oxidizing Activity.
AB  - In our previous study, the multicomponent monooxygenase DsoABCDEF in
      Acinetobacter sp. strain 20B was cloned based on its ability to oxidize dimethyl
      sulfide (DMS) to dimethyl sulfoxide (DMSO) in E. coli cells, which had high
      sequence similarity with phenol hydroxylase MopKLMNOP in Acinetobacter
      calcoaceticus NCIB8250, DmpKLMNOP in Pseudomonas sp. CF600 and some other
      multicomponent monooxygenases. In this study, DsoB, C, D, E, and F were found to
      be needed for DMS-oxidizing activity in polypeptide requirement experiments,
      while DsoA was not necessary for it. It was also found that complementation of
      the deletion mutants lacking DsoC or F with the corresponding Dmp polypeptides
      supported the DMS-oxidizing activity, while complementation of the deletion
      mutants lacking any of the oxygenase subunits (DsoB, D, or E) with the
      corresponding Dmp polypeptides reduced or nullified the activity. 

PMID- 26300167
TI  - Absolute Configuration of Kelsoene and Prespatane.
AB  - The absolute configurations of the rare sesquiterpenes, kelsoene and prespatane,
      were determined to be (1S, 2R,5S, 6S, 7R, 8R)-2,8-dimethyl-6-(1
      methylethenyl)tricyclo[5.3.0.0(2,5)] decane (IUPAC name) and (1R, 2S, 5R, 6R, 7R,
      8S)-1,5-dimethyl-8-(1-methylethenyl) tricyclo-[5.3.0.0(2,6)] decane,
      respectively, on the basis of the observed chemical shifts and NOEs in NOESY and
      NOEDS experiments after conversion with the chiral reagent, 2'-methoxy-1,1'
      binaphthalene-2-carbohydroximoyl chloride (MBCC). The absolute configurations of
      kelsoene and prespatane thus determined suggest that initial cyclization of FPP
      from the si-face at C-10 to form a 10R-germacradienyl cation leads to kelsoene,
      while that from the re-face leads to prespatane via the 10S-germacradienyl
      cation. 

PMID- 26300168
TI  - Accumulation of Isohemigossypolone and Its Related Compounds in the Inner Bark
      and Heartwood of Diseased Pachira aquatica.
AB  - Isohemigossypolone (1) and 2-O-methylisohemigossypolone (2), major fungitoxins of
      Pachira aquatica, were found to accumulate locally in the outer bark of the
      swollen trunk, whereas the inner bark and heartwood contained only a trace amount
      of them. From P. aquatica that was infected with a phytopathogenic bacterium, we
      detected significant amounts of 1 and 2 from browned inner tissues of the swollen
      trunk. According to a quantitative analysis by a gas-chromatograph, the
      concentration of 1 in the diseased inner tissues was calculated to be
      approximately 780 MUg/g f.w., which was the same level as that in the outer bark
      of healthy individuals. These findings suggest that the inner tissues inducibly
      produced and accumulated antifungals 1 and 2 during infection events, as do many
      plants with phytoalexins. 11-Nor-2-O-methylisohemigossypolone (3), showing
      approximately equivalent fungitoxic activity to that of 1 and 2, was also
      isolated from the infected inner tissues. We screened pathogenic bacteria from
      the infected tissue, and isolated a rod-shaped bacterium that was tentatively
      identified as Pseudomonas sp. which promoted tissue-browning on sectioned disks
      of P. aquatica trunks. 

PMID- 26300169
TI  - Isolation and Characterization of Basic Exochitinase from Leaf Extract of
      Rehmannia glutinosa.
AB  - Rehmannia chitinases were extracted from the leaves of Rehmannia glutinosa under
      acidic conditions (pH 2.9). We purified a 28.6-kDa chitinase, designated as P2,
      from crude extract to homogeneity by (NH4)2SO4 precipitation, chromatography with
      regenerated chitin affinity and hydrophobic interaction column, and preparative
      native PAGE. Isolated P2 showed maximum chitinase activity at pH 5.0 and 60
      degrees C, and had a isoelectric point of 8.46. P2 produced only (GlcNAc)2 from
      (GlcNAc)4-6 and regenerated chitin. Based on these results, we arrived at the
      conclusion that P2 was a basic exochitinase. 

PMID- 26300170
TI  - Stability of Lutein and Its Myristate Esters.
AB  - Stabilities of lutein and its myristate esters against heat and UV light were
      studied by HPLC response. Free lutein (FL) was very unstable against heat; lutein
      monomyristate (LM), slightly stable; and lutein dimyristate (LD), very stable.
      Both LM and LD were more stable toward UV light than FL. These results suggest
      that esterification of the OH group with a fatty acid might stabilize lutein
      against heat and UV-light degradation. 

PMID- 26300171
TI  - Clerodendrin I, a New Neoclerodane Diterpenoid from Clerodendron trichotomum.
AB  - A new neoclerodane diterpenoid, clerodendrin I, was isolated from leaves of
      Clerodendron trichotomum as a feeding stimulant of the turnip sawfly, Athalia
      rosae ruficornis, and characterized as a threo epimer of clerodendrin F in the
      2,3-diacetoxy-2-methylbutanoyloxy moiety at the C-3beta position. 

PMID- 26300172
TI  - Oxidation of Two Pregnane Steroids Catalyzed by the Fungus Cephalosporium
      aphidicola.
AB  - Two pregnane steroids, pregnane (1) and 3beta-hydroxypregnane (2), were oxidized
      by fermentation with the fungus Cephalosporium aphidicola. The fermentation of
      pregnane (1) yielded 3beta-hydroxypregnane (2) and 3beta, 6beta,11alpha
      trihydroxypregnane (3), while that of 3beta-hydroxypregnane (2) afforded
      6beta,11alpha-dihydroxypregn-3,20-dione (4), 3beta,6beta,15alpha-trihydroxypregn
      20-one (5) and 3beta,5alpha,11alpha-trihydroxypregn-20-one (6). The metabolites
      are characterized by detailed physical and spectroscopic studies. 

PMID- 26300173
TI  - Identification of Trace Sterols in the Seeds of Foxtail Millet (Setaria italica
      Beauv.).
AB  - Trace sterols in the seeds of foxtail millet (Setaria italica Beauv.) were
      investigated by GC-MS. Eleven of these trace sterols, i.e., brassicasterol,
      episterol, 24-methyllathosterol, 24-ethyllathosterol, avenasterol, 24
      methylenecholesterol, fucosterol, isofucosterol, 24-methyl-5alpha-cholest-24(28)
      en-3beta-ol, 24-ethyl-5alpha-cholest-24(28)Z-en-3beta-ol, and 24
      ethyldesmosterol, were identified, suggesting that the previously reported high
      content of sitostanol was possibly contaminated with a small amount of
      isofucosterol. 

PMID- 26300174
TI  - Chemical Characterization of Fucoidan from Commercially Cultured Nemacystus
      decipiens (Itomozuku).
AB  - Fucoidan was isolated from Nemacystus decipiens KUCKUCK which is commercially
      cultured at the rate of about 2,000 t/year in fields of the Okinawa Islands, in
      Japan. The yield of fucoidan extracted by 0.1 M HCl was 0.5% (W/W) based on the
      wet algae. The total carbohydrate, sulfuric acid, ash, and moisture in fucoidan
      was 65.8, 30.8, 22.3, and 3.8%, respectively. Fucose and galactose were
      identified by liquid chromatography. The molar ratio of the sugar residues in the
      fucoidan was estimated to be L-fucose:D-galactose:sulfuric acid=1.0:0.05:1.0. The
      optical rotation of the fucoidan (0.4%) showed a value of -0.315 degrees  at 60
      degrees C, then it decreased a little with decreasing temperature. The infrared
      spectrum of isolated fucoidan is in agreement with that of standard fucoidan. The
      molecular mass of fucoidan was estimated to be 2.4*10(5). The (1)H- and (13)C-NMR
      spectral data suggest that fucoidan is mainly composed of L-fucopyranose, 2-mono
      O-sulfo-L-fucopyranose, 4-mono-O-sulfo-L-fucopyranose, and 2,4-di-O-sulfo-L
      fucopyranose. 

PMID- 26300175
TI  - Effect of Optically Active Ethyl 2-Phthalimidooxypropionate on the Growth of
      Cress, Lepidium sativum.
AB  - The effects of 2-phthalimidooxyalkanoic acid derivatives on the germination and
      root-growth of cress were examined. Since 2-phthalimidooxypropionates were most
      effective, the optically active ethyl esters were prepared. As the result of
      biological testing, the (S)-(-)-isomer exhibited stronger activity than the (R)
      (+)-isomer. This result is contrary to those from commercial herbicides with
      similar structures, phenoxy- and oxyphenoxy-propionate-type compounds, where the
      (R)-isomers are generally known to be the active principles. 

PMID- 26300176
TI  - Synthesis of 2-(4-Hydroxyphenyl)naphthalene-1,8-dicarboxylic Anhydride, a
      Phytoalexin Isolated from Unripe Banana (Musa acuminata).
AB  - 2-(4-Hydroxyphenyl)naphthalene-1,8-dicarboxylic anhydride, a component of the
      phytoalexin that has been isolated from the peel of unripe banana (Musa
      acuminata), was synthesized from 3-bromoacenaphthene. 

PMID- 26300177
TI  - Saponin Stimulates Fruiting of the Edible Basidiomycete Pleurotus ostreatus.
AB  - The addition of saponin from Quillaja to malt extract agar dramatically
      stimulated fruit body development of Pleurotus ostreatus. Higher concentration of
      Quillaja saponin added to the medium suppressed the growth of pilei of fruit
      bodies. The results indicate that the triterpenoid-saponin is a bioactive
      substance for fruiting of P. ostreatus. 

PMID- 26300178
TI  - Preparation and Characterization of Fully Active Biotinylated Analogs of
      Phytosulfokine-alpha.
AB  - We report the preparation of biotinylated analogs of phytosulfokine-alpha
      (Tyr(SO3H)-Ile-Tyr(SO3H)-Thr-Gln; PSK-alpha), an endogenous peptide growth factor
      in plants. Because the modification of the N-terminal amino group leads to
      significant loss of the activities, a Lys residue was incorporated in the C
      terminal region of PSK-alpha, and its e amino group was reacted with
      biotinylation reagent. Results of the binding assay showed that [N(epsilon)
      (biotinyl)Lys(5)]PSK-alpha retained the same binding activity and mitogenic
      activity as that of native PSK-alpha. Insertion of a single or double 6
      aminohexanoic acid spacer between the epsilon amino group of Lys(5) and the
      carboxyl group of biotin did not significantly alter the activities of
      biotinylated [Lys(5)]PSK-alpha. Structure-activity information obtained here
      would be useful for the detection and isolation of PSK-alpha receptors. 

PMID- 26300179
TI  - A microporous metal-organic framework with polarized trifluoromethyl groups for
      high methane storage.
AB  - A novel NbO-type metal-organic framework UTSA-88a with polarized trifluoromethyl
      groups exhibits a notably high methane storage capacity of 248 cm(3) (STP) cm(-3)
      (at room temperature and 65 bar) and a working capacity of 185 cm(3) (STP) cm(
      3). 

PMID- 26300180
TI  - A hexangular ring-core NiCo2O4 porous nanosheet/NiO nanoparticle composite as an
      advanced anode material for LIBs and catalyst for CO oxidation applications.
AB  - A porous hexangular ring-core NiCo2O4 nanosheet/NiO nanoparticle composite has
      been synthesized using a hydrothermal method followed by an annealing process in
      air. The as-obtained composite as an anode material exhibits a high initial
      discharge capacity of 1920.6 mA h g(-1) at a current density of 100 mA g(-1) and
      the capacity is retained at 1567.3 mA h g(-1) after 50 cycles. When it is
      utilized as a catalyst for CO oxidation, complete CO conversion is achieved at
      115  degrees C and a catalytic life test demonstrates the good stability of the
      composite. 

PMID- 26300181
TI  - In vitro seizure like events and changes in ionic concentration.
AB  - BACKGROUND: In vivo, seizure like events are associated with increases in
      extracellular K(+) concentration, decreases in extracellular Ca(2+)
      concentration, diphasic changes in extracellular sodium, chloride, and proton
      concentration, as well as changes of extracellular space size. These changes
      point to mechanisms underlying the induction, spread and termination of seizure
      like events. METHODS: We investigated the potential role of alterations of the
      ionic environment on the induction of seizure like events-considering a review of
      the literature and own experimental work in animal and human slices. RESULTS:
      Increasing extracellular K(+) concentration, lowering extracellular Mg(2+)
      concentration, or lowering extracellular Ca(2+) concentration can induce seizure
      like events. In human tissue from epileptic patients, elevation of K(+)
      concentration induces seizure like events in the dentate gyrus and subiculum. A
      combination of elevated K(+) concentration and 4-AP or bicuculline can induce
      seizure like events in neocortical tissue. CONCLUSIONS: These protocols provide
      insight into the mechanisms involved in seizure initiation, spread and
      termination. Moreover, pharmacological studies as well as studies on mechanisms
      underlying pharmacoresistance are feasible.

PMID- 26300182
TI  - The use of a viral 2A sequence for the simultaneous over-expression of both the
      vgf gene and enhanced green fluorescent protein (eGFP) in vitro and in vivo.
AB  - INTRODUCTION: The viral 2A sequence has become an attractive alternative to the
      traditional internal ribosomal entry site (IRES) for simultaneous over-expression
      of two genes and in combination with recombinant adeno-associated viruses (rAAV)
      has been used to manipulate gene expression in vitro. NEW METHOD: To develop a
      rAAV construct in combination with the viral 2A sequence to allow long-term over
      expression of the vgf gene and fluorescent marker gene for tracking of the
      transfected neurones in vivo. RESULTS: Transient transfection of the AAV plasmid
      containing the vgf gene, viral 2A sequence and eGFP into SH-SY5Y cells resulted
      in eGFP fluorescence comparable to a commercially available reporter construct.
      This increase in fluorescent cells was accompanied by an increase in VGF mRNA
      expression. Infusion of the rAAV vector containing the vgf gene, viral 2A
      sequence and eGFP resulted in eGFP fluorescence in the hypothalamus of both mice
      and Siberian hamsters, 32 weeks post infusion. In situ hybridisation confirmed
      that the location of VGF mRNA expression in the hypothalamus corresponded to the
      eGFP pattern of fluorescence. COMPARISON WITH OLD METHOD: The viral 2A sequence
      is much smaller than the traditional IRES and therefore allowed over-expression
      of the vgf gene with fluorescent tracking without compromising viral capacity.
      CONCLUSION: The use of the viral 2A sequence in the AAV plasmid allowed the
      simultaneous expression of both genes in vitro. When used in combination with
      rAAV it resulted in long-term over-expression of both genes at equivalent
      locations in the hypothalamus of both Siberian hamsters and mice, without any
      adverse effects.

PMID- 26300183
TI  - EEG source localization: Sensor density and head surface coverage.
AB  - BACKGROUND: The accuracy of EEG source localization depends on a sufficient
      sampling of the surface potential field, an accurate conducting volume estimation
      (head model), and a suitable and well-understood inverse technique. The goal of
      the present study is to examine the effect of sampling density and coverage on
      the ability to accurately localize sources, using common linear inverse weight
      techniques, at different depths. Several inverse methods are examined, using the
      popular head conductivity. NEW METHOD: Simulation studies were employed to
      examine the effect of spatial sampling of the potential field at the head
      surface, in terms of sensor density and coverage of the inferior and superior
      head regions. In addition, the effects of sensor density and coverage are
      investigated in the source localization of epileptiform EEG. RESULTS: Greater
      sensor density improves source localization accuracy. Moreover, across all
      sampling density and inverse methods, adding samples on the inferior surface
      improves the accuracy of source estimates at all depths. COMPARISON WITH EXISTING
      METHODS: More accurate source localization of EEG data can be achieved with high
      spatial sampling of the head surface electrodes. CONCLUSIONS: The most accurate
      source localization is obtained when the voltage surface is densely sampled over
      both the superior and inferior surfaces.

PMID- 26300185
TI  - Editorial: Families and Aging: From Private Troubles to a Global Agenda.

PMID- 26300184
TI  - Combining micro-computed tomography with histology to analyze biomedical implants
      for peripheral nerve repair.
AB  - BACKGROUND: Biomedical implants used in tissue engineering repairs, such as
      scaffolds to repair peripheral nerves, can be too large to examine completely
      with histological analyses. Micro-computed tomography (micro-CT) with contrast
      agents allows ex vivo visualization of entire biomaterial implants and their
      interactions with tissues, but contrast agents can interfere with histological
      analyses of the tissues or cause shrinkage or loss of antigenicity. NEW METHOD:
      Soft tissue, ex vivo micro-CT imaging using Lugol's iodine was compatible with
      histology after using a rapid (48 h) method of removing iodine. RESULTS: Adult
      normal and repaired rat sciatic nerves were infiltrated ex vivo with iodine,
      imaged with micro-CT and then the iodine was removed by incubating tissues in
      sodium thiosulfate. Subsequent paraffin sections of normal nerve tissues showed
      no differences in staining with hematoxylin and eosin or immunostaining with
      multiple antibodies. Iodine treatment and removal did not alter axonal diameter,
      nuclear size or relative area covered by immunostained axons (p>0.05). Combining
      imaging modalities allowed comparisons of macroscopic and microscopic features of
      nerve tissues regenerating through simple nerve conduits or nerve conduits
      containing a titanium wire for guidance. COMPARISON WITH EXISTING METHODS:
      Quantification showed that treatment with iodine and sodium thiosulfate did not
      result in tissue shrinkage or loss of antigenicity. CONCLUSIONS: Because this
      combination of treatments is rapid and does not alter tissue morphology, this
      expands the ex vivo methods available to examine the success of biomaterial
      implants used for tissue engineering repairs.

PMID- 26300188
TI  - Families, Intergenerational Bonds, and Aging in Sub-Saharan Africa.
AB  - This Research Note proposes a rationale, and offers a set of initial parameters,
      for an explicit effort to forge a policy and scientifically relevant family
      gerontology for Africa. It builds on a critical appraisal of dominant policy
      discourses in the region and existing research efforts on families and aging,
      specifically in sub-Saharan Africa.

PMID- 26300187
TI  - Care Ideals in the Netherlands: Shifts between 2002 and 2011.
AB  - Our study's premise was that normative care beliefs can inform the current care
      policy debate. We conducted latent class regression analyses on two waves of
      Netherlands Kinship Panel Study data (n = 4,163) to distinguish care ideals that
      captured multiple dimensions of normative care beliefs simultaneously. We also
      assessed how these care ideals have shifted in the early twenty-first century. We
      distinguished four care ideals: warm-modern (family and state jointly responsible
      for caring, egalitarian gender roles), cold-modern (large state responsibility,
      restricted family responsibility, egalitarian gender roles), traditional
      (restricted state responsibility, large family responsibility, moderately
      traditional gender roles), and cold-traditional (large state responsibility,
      restricted family responsibility, traditional gender roles). Between 2002 and
      2011, there has been a shift away from warm-modern care ideals and towards cold
      modern care ideals. This is remarkable, because Dutch policy makers have
      increasingly encouraged family members to take on an active role in caring for
      dependent relatives.

PMID- 26300189
TI  - Challenges for the Aging Family in the People's Republic of China.
AB  - The People's Republic of China has the largest population of older persons of any
      country in the world. It is a nation that has experienced enormous economic,
      social, and demographic changes over the past three and a half decades.
      Traditionally, the family was the main social support for older persons; this
      changed somewhat under early socialism, but in recent years, the importance of
      family support has been reasserted. However, over this time, the family's ability
      to support its older members has been considerably altered and arguably weakened.
      This article reviews four key issues (population change, the hukou system,
      economic reform, general features surrounding modernization) that have gradually
      changed families' capacity to provide support for older members. Research foci
      and public policy directions are considered under which the state might take some
      responsibilities from the family, support capacity to care, and improve the
      quality and quantity of support for older citizens.

PMID- 26300190
TI  - Diverse Family Structures and the Care of Older Persons.
AB  - Demographic and social trends lead to a variety of micro-level and internal
      structural contexts that influence caregiving in families with older members. The
      results of macro-level changes have received little focused attention in the
      aging literature, where much of the caregiving research has addressed issues
      within the context of traditional family structure. Yet the conventional nuclear
      family model is increasingly uncommon as new, pluralistic models of family life
      are emerging in contemporary society. The majority of elder care is provided by
      relatives, albeit with varying patterns of involvement and responsibility across
      family structures. Both conventional and pluralistic families face challenges in
      meeting the care needs of their oldest members, leaving some older adults at risk
      of having unmet needs. Additional research on family risk and resilience related
      to the care of older relatives is warranted, particularly with respect to
      pluralistic models of family life.

PMID- 26300191
TI  - Intra-couple Caregiving of Older Adults Living Apart Together: Commitment and
      Independence.
AB  - Recently, rising numbers of mid-life and older adults are starting a "living
      apart together" (LAT) relationship following divorce or widowhood. LAT describes
      an intimate relationship wherein partners maintain separate households. This
      study investigated the characteristics of care arrangements in older long-term
      LAT couples and elicited personal comments about intra-couple care. We
      interviewed 25 LAT partners and a comparison group of 17 remarried older adults
      in the Netherlands in a side study of the Netherlands Kinship Panel Study.
      Results showed that about half of the LAT partners intended to exchange care if
      needed (partnership commitment); the other half had ambiguous feelings or
      intentions to refuse care (independence orientation). However, for those LAT
      partners already confronted with illness in their current relationship, all
      provided care to the partner in need. The minority of LAT partners who would not
      exchange care reciprocally are more likely to give as opposed to receive care.

PMID- 26300192
TI  - Mining a Unique Canadian Resource: The Canadian Longitudinal Study on Aging.

PMID- 26300194
TI  - "People are Getting Lost a Little Bit": Systemic Factors that Contribute to Falls
      in Community-Dwelling Octogenarians.
AB  - Octogenarians living in the community are the fastest-growing demographic in
      Canada. Simultaneously, they have the highest prevalence of falls and nine times
      greater risk of injury due to a fall. To understand how to improve the safety of
      octogenarians' aging-in-place, a systems approach is essential. Understanding how
      societal factors interact and affect the older adult can help care custodians
      identify and remove safety deficiencies that bring about falls. The purpose of
      this study was to identify system-wide factors contributing to falls in community
      dwelling octogenarians. Eight falls were investigated using the systemic falls
      investigative method. Participants ranged in age from 83-90 years. Across-case
      analyses identified 247 contributing factors, grouped within four distinct
      themes: (a) everyday living has become risky; (b) supervision limitations; (c)
      health care system disconnects; and (d) poor fall risk identification and follow
      up. This qualitative study provides systemic insights into how and why falls
      occur in community-dwelling octogenarians.

PMID- 26300195
TI  - First Light After the Long Night: A Follow-up Report of the Randomized FHN
      Nocturnal Trial.

PMID- 26300196
TI  - Acid-Base Status and Mortality Risk in Hemodialysis Patients.

PMID- 26300197
TI  - The DOPPS Practice Monitor for US Dialysis Care: PTH Levels and Management of
      Mineral and Bone Disorder in US Hemodialysis Patients.

PMID- 26300198
TI  - Treatment of Hyponatremic Encephalopathy.

PMID- 26300199
TI  - In Reply to 'Treatment of Hyponatremic Encephalopathy'.

PMID- 26300200
TI  - Quiz Page September 2015: Acute Kidney Injury Following Gastric Bypass.

PMID- 26300201
TI  - AJKD Atlas of Renal Pathology: Congenital Nephrotic Syndrome of Finnish Type.

PMID- 26300202
TI  - AJKD Atlas of Renal Pathology: C1q Nephropathy.

PMID- 26300203
TI  - AJKD Atlas of Renal Pathology: Membranous Nephropathy.

PMID- 26300204
TI  - AJKD Atlas of Renal Pathology: Membranoproliferative Glomerulonephritis.

PMID- 26300205
TI  - AJKD Atlas of Renal Pathology: Dense Deposit Disease.

PMID- 26300206
TI  - Rivaroxaban-induced hair loss.

PMID- 26300207
TI  - Use of over-the-counter (OTC) drugs and perceptions of OTC drug safety among
      German adults.
AB  - PURPOSE: In Europe, little empirical evidence is available about over-the-counter
      (OTC) drug consumption and risk perceptions. The objective of this study was to
      describe consumers' OTC drug use and perceptions of OTC drug safety in Germany.
      METHODS: An online survey based on a quota sample with combined strata for age,
      gender, and education of 300 adult German participants was conducted in June and
      July 2013. The survey questionnaire covered the participants' OTC and
      prescription drug use, risk perceptions of OTC and prescription drugs, package
      leaflet reading habits, and OTC drug off-label use. RESULTS: Seven day
      prevalences of OTC drug use were higher in women (52.0%) than in men (40.8%). The
      risk perception of specific OTC drugs was impacted by the route of
      administration, the indication, and the drugs' ingredients. Products for dermal
      application or plant-based products were considered 'rather not risky' by 82.7
      96.6 of the participants, depending on the product. Products for oral use or
      chemically synthesized substances were considered less safe. While 48.0% of
      consumers reported always reading the package leaflet of OTC drugs, 44.5%
      reported not reading it if they knew the drug or believed the drug was very safe.
      People, 60 years and older, reported significantly lower levels of OTC drug off
      label use (9.3%) than younger people (22.0%). CONCLUSIONS: The 7-day prevalence
      of OTC drug use in Germany is high, especially among women. Consumers generally
      have balanced perceptions regarding OTC drug safety. Behaviours and knowledge
      related to OTC drug use should be considered by health care providers and
      regulators.

PMID- 26300208
TI  - Comment on Christiansen et al.: When food met pharma.

PMID- 26300209
TI  - Evaluation of [(11)C]methyl-losartan and [(11)C]methyl-EXP3174 for PET imaging of
      renal AT1receptor in rats.
AB  - INTRODUCTION: The angiotensin II type 1 receptor (AT1R) is responsible for the
      main effects of the renin-angiotensin system (RAS), and its expression pattern is
      altered in several diseases. The [(11)C]methylated derivatives of the clinically
      used AT1R blocker (ARB) losartan and its active metabolite EXP3174, that binds
      with higher affinity to AT1R, were evaluated as potential PET imaging tracers in
      rat kidneys. METHODS: [(11)C]Methyl-losartan and [(11)C]methyl-EXP3174 were
      synthesized by [(11)C]methylation of the tetrazole-protected analogs using
      [11C]methyl iodide. Tissue uptake and binding selectivity of [(11)C]methyl
      losartan were assessed by ex-vivo biodistribution and in-vitro autoradiography.
      Radiolabeled metabolites in rat plasma and kidneys were analysed by column-switch
      HPLC. Both tracers were evaluated with small animal PET imaging. Due to better
      pharmacokinetics, [(11)C]methyl-EXP3174 was further investigated via PET by co
      injection with AT1R antagonist candesartan or the AT2R antagonist PD123,319.
      RESULTS: Binding selectivity to renal AT1 over AT2 and Mas receptors was
      demonstrated for [(11)C]methyl-losartan. Plasma metabolite analysis at 10 min
      revealed stability of [(11)C]methyl-losartan and [(11)C]methyl-EXP3174 with the
      presence of unchanged tracer at 70.8 +/- 9.9% and 81.4 +/- 6.0%, of total
      radioactivity, respectively. Contrary to [(11)C]methyl-losartan, co-injection of
      candesartan with [(11)C]methyl-EXP3174 reduced the proportion of unchanged tracer
      (but not metabolites), indicating that these metabolites do not bind to AT1R in
      rat kidneys. MicroPET images for both radiotracers displayed high kidney-to
      background contrast. Candesartan significantly reduced [(11)C]methyl-EXP3174
      uptake in the kidney, whereas no difference was observed following PD123,319
      indicating binding selectivity for AT1R. CONCLUSIONS: [(11)C]Methyl-EXP3174
      displayed a favorable binding profile compared to [(11)C]methyl-losartan for
      imaging renal AT1Rs supporting further studies to assess its full potential as a
      quantitative probe for AT1R via PET.

PMID- 26300210
TI  - In vivo inhibition of neutral endopeptidase enhances the diagnostic potential of
      truncated gastrin (111)In-radioligands.
AB  - INTRODUCTION: Radiolabeled gastrin analogs represent attractive candidates for
      diagnosis and therapy of cholecystokinin subtype-2 receptor (CCK2R)-expressing
      tumors. Radiolabeled des(Glu)5-gastrins show favorably low renal accumulation,
      but localize poorly in CCK2R-positive lesions. We introduce herein three
      truncated [DOTA-DGlu(10)]gastrin(10-17) analogs, with oxidation-susceptible
      Met(15) replaced by: (1), (2), or (3), and study the profile of [(111)In]1/2/3
      during in vivo inhibition of neutral endopeptidase (NEP) in comparison to the non
      truncated [ ([(111)In]4) reference. METHODS: Blood samples collected from mice 5
      min postinjection (pi) of [(111)In]1/2/3/4 without or with phosphoramidon (PA)
      coinjection were analyzed by RP-HPLC. Biodistribution was conducted in SCID mice
      bearing A431-CCK2R(+) or AR42J xenografts 4h after administration of
      [(111)In]1/2/3/4 without or with PA coinjection. RESULTS: Firstly, we observed
      remarkable increases in the amount of radiopeptides detected intact in the blood
      of PA-treated mice at 5 min pi compared to controls. Secondly, we noted
      impressive enhancement of [(111)In]1/2/3 localization in AR42J and A431-CCK2R(+)
      tumors in mice after PA coinjection. Specifically, the uptake of [(111)In]1 at 4h
      pi increased from 2.6 +/- 0.3%ID/g to 13.3 +/- 3.5%ID/g in the AR42J tumors and
      from 4.3 +/- 0.6%ID/g to 20.4 +/- 3.6%ID/g in the A431-CCK2R(+) xenografts, with
      comparable improvements noted for [(111)In]2 and [(111)In]3 as well. Thirdly,
      renal uptake remained favorably low and unaffected by PA (<2.5%ID/g). Conversely,
      although the stability and tumor targeting of [(111)In]4 improved, its high renal
      uptake (>85%ID/g) increased even further by PA (>140%ID/g). CONCLUSIONS: In situ
      inhibition of NEP represents a promising new tool to enhance the diagnostic
      efficacy of biodegradable gastrin radioligands in the visualization of CCK2R
      positive lesions in man.

PMID- 26300212
TI  - Imaging real-time HIV-1 virion fusion with FRET-based biosensors.
AB  - We have produced a novel, simple and rapid method utilising genetically encodable
      FRET-based biosensors to permit the detection of HIV-1 virion fusion in living
      cells. These biosensors show high sensitivity both spatially and temporally, and
      allow the real-time recovery of HIV-1 fusion kinetics in both single cells and
      cell populations simultaneously. 

PMID- 26300211
TI  - Evolution of a Unified Strategy for Complex Sesterterpenoids: Progress toward
      Astellatol and the Total Synthesis of (-)-Nitidasin.
AB  - Astellatol and nitidasin belong to a subset of sesterterpenoids that share a
      sterically encumbered trans-hydrindane motif with an isopropyl substituent. In
      addition, these natural products feature intriguing polycyclic ring systems,
      posing significant challenges for chemical synthesis. Herein, the evolution of
      our stereoselective strategy for isopropyl trans-hydrindane sesterterpenoids is
      detailed. These endeavors included the synthesis of several building blocks,
      enabling studies toward all molecules of this terpenoid subclass, and of advanced
      intermediates of our initial route toward a biomimetic synthesis of astellatol.
      These findings provided the basis for a second-generation and a third-generation
      approach toward astellatol that eventually culminated in the enantioselective
      total synthesis of (-)-nitidasin. In particular, a series of substrate-controlled
      transformations to install the ten stereogenic centers of the target molecule was
      orchestrated and the carbocyclic backbone was forged in a convergent fashion.
      Furthermore, the progress toward the synthesis of astellatol is disclosed and
      insights into some observed yet unexpected diastereoselectivities by detailed
      quantum-mechanical calculations are provided. 

PMID- 26300213
TI  - Fractional exhaled nitric oxide (FeNO) among office workers in an academic
      institution, Malaysia--associations with asthma, allergies and office
      environment.
AB  - OBJECTIVE: There are few studies on fractional exhaled nitric oxide (FeNO) and
      respiratory symptoms among adults in tropical areas. The aim was to study
      associations between FeNO and selected personal factors, respiratory symptoms,
      allergies, office characteristics and indoor office exposures among office
      workers (n = 460) from a university in Malaysia. METHODS: Information on health
      was collected by a questionnaire, skin prick test and FeNO measurement.
      Temperature, relative air humidity, carbon monoxide and carbon dioxide were
      measured in the offices. Settled dust was vacuumed in the offices and analyzed
      for endotoxin, (1,3)-beta-glucan and house dust mites allergens, namely
      Dermatophagoides pteronyssinus (Der p 1) and Dermatophagoides farinae (Der f 1).
      Two-level linear mixed models and multiple logistic regression were used to
      analyze the associations. RESULTS: One-fourth (25.9%) of the office workers had
      elevated FeNO level (>= 25 ppb) and 61.5% had HDM, cat, seafood or pollen
      allergy. Male gender (p < 0.001), current smoking (p = 0.037), height (p < 0.001)
      and atopy (p < 0.001) were associated with FeNO. The amount of vacuumed dust was
      associated with FeNO among atopic subjects (p = 0.009). Asthma and rhinitis
      symptoms were associated with FeNO (p < 0.05), especially among atopic subjects.
      In particular, a combination of atopy and elevated FeNO were associated with
      doctor-diagnosed asthma (p < 0.001), rhinitis (p < 0.001) and airway symptoms
      last 12 months (p < 0.001). CONCLUSION: Gender, smoking, height and atopy are
      important risk factors for elevated FeNO levels. A combination of allergy testing
      and FeNO measurement could be useful in respiratory illness epidemiology studies
      and patient investigations in tropical areas.

PMID- 26300214
TI  - Detrusor after-contraction on ambulatory urodynamics in symptomatic women.
AB  - OBJECTIVES: To investigate the association between detrusor after-contraction and
      urodynamic parameters in a cohort of patients undergoing urodynamic studies by
      ambulatory monitoring. METHODS: All symptomatic adult female patients with non
      neurogenic lower urinary tract dysfunction having ambulatory monitoring over the
      period January 1998 to January 2014 were included. Urodynamic traces were
      reviewed to identify detrusor after-contraction. Measured urodynamic variables
      were Qmax (mL/s), V(void) (mL) and P(det.Qmax) (cmH(2)O). Student's unpaired t
      test was used to compare the mean of the variable in the detrusor after
      contraction and non-detrusor after-contraction groups. RESULTS: We identified 331
      women with a median age of 50 years (range 16-82). Detrusor after-contraction was
      seen after at least one void in 122 patients giving a prevalence of 37%. A total
      of 167 (51%) patients had detrusor overactivity. Diagnosis of detrusor
      overactivity was associated with the presence of detrusor after-contraction (P <
      0.05). Overall, patients with detrusor after-contraction had a statistically
      higher mean P(det.Qmax) (32 vs 28 cmH(2)O, P = 0.04) and lower mean voided volume
      (300 vs 378 mL, P < 0.001). CONCLUSION: These findings suggest a relatively high
      prevalence of detrusor after-contraction during ambulatory monitoring, and an
      association between detrusor overactivity, V(void), P(det.Qmax) and detrusor
      after-contraction recorded during ambulatory monitoring. Therefore, a link
      between detrusor after-contractions and the syndrome of overactive bladder can be
      postulated.

PMID- 26300216
TI  - Anesthetic "Conditioning:" A Continuing Question of Clinical Relevance.

PMID- 26300215
TI  - Pseudohallucinations After Cardiac Surgery.

PMID- 26300217
TI  - Assessing Effect of Remote Ischemic Preconditioning on Postoperative Cognitive
      Function After Cardiac Surgery Using Cardiopulmonary Bypass.

PMID- 26300219
TI  - To reduce or abstain? Substance use goals in the treatment of veterans with
      substance use disorders and comorbid PTSD.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) and substance use disorders
      (SUD) frequently co-occur. Previous research demonstrates the utility of goals in
      attaining improved SUD outcomes, however, no previous studies have examined goal
      choices in the context of integrated treatment for comorbid PTSD and SUD.
      OBJECTIVES: The present study investigated correlates of treatment entry goals to
      either reduce or abstain from substance use. METHODS: Participants (N = 60) were
      treatment-seeking veterans with current PTSD and SUD. Participants completed self
      report and clinician-rated measures of substance use, PTSD, and affective
      symptoms as part of a larger randomized controlled trial. RESULTS: Half (30/60)
      of participants endorsed a treatment entry goal to reduce substance use
      (reducers). Compared to participants who endorsed a treatment entry goal of
      abstinence (abstainers), reducers were significantly younger, more likely to be
      employed, more likely to have served in recent military conflicts (Operations
      Enduring/Iraqi Freedom), and endorsed significantly fewer symptoms of alcohol
      dependence. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: The findings demonstrate
      clinically relevant differences based on treatment entry goals, suggesting that
      individuals are often able to choose conceivably appropriate treatment goals
      based, most notably, on the severity of their SUD. Collaboratively engaging
      patients in establishing treatment goals that are consistent with their beliefs
      and desires in conjunction with empirical findings is particularly relevant in
      the context of treatment for SUD and PTSD where many patients are ambivalent
      about treatment and attrition is common.

PMID- 26300218
TI  - Clear Cell Renal Cell Carcinoma Subtypes Identified by BAP1 and PBRM1 Expression.
AB  - PURPOSE: In clear cell renal cell carcinoma BAP1 and PBRM1 are 2 of the most
      commonly mutated genes (10% to 15% and 40% to 50%, respectively). We sought to
      determine the prognostic significance of PBRM1 and BAP1 expression in clear cell
      renal cell carcinoma. MATERIALS AND METHODS: We used immunohistochemistry to
      assess PBRM1 protein expression in 1,479 primary clear cell renal cell carcinoma
      tumors that were previously stained for BAP1. A centralized pathologist reviewed
      all cases and categorized tumors as positive or deficient for PBRM1 and BAP1.
      Kaplan-Meier and Cox regression models were used to evaluate association of PBRM1
      and BAP1 expression with the risk of death from renal cell carcinoma and the risk
      of metastasis after adjustment for age and the Mayo Clinic SSIGN (stage, size,
      grade and necrosis) score. RESULTS: PBRM1 and BAP1 expression was PBRM1+ BAP1+ in
      40.1% of tumors, PBRM1- BAP1+ in 48.6%, PBRM1+ BAP1- in 8.7% and PBRM1- BAP1- in
      1.8%. The incidence of PBRM1 and BAP1 loss in the same tumor was significantly
      lower than expected (actual 1.8% vs expected 5.3%, p <0.0001). Compared to
      patients with PBRM1+ BAP1+ tumors those with PBRM1- BAP1+ lesions were more
      likely to die of renal cell carcinoma (HR 1.39, p = 0.035), followed by those
      with PBRM1+ BAP1- and PBRM1- BAP1- tumors (HR 3.25 and 5.2, respectively, each p
      <0.001). PBRM1 and BAP1 expression did not add independent prognostic information
      to the SSIGN score. CONCLUSIONS: PBRM1 and BAP1 expression identified 4 clinical
      subgroups of patients with clear cell renal cell carcinoma who had divergent
      clinical outcomes. The clinical value of these biomarkers will be fully realized
      when therapies targeting pathways downstream of PBRM1 and BAP1 are developed.

PMID- 26300220
TI  - Smoking Gun or Circumstantial Evidence? Comparison of Statistical Learning
      Methods using Functional Annotations for Prioritizing Risk Variants.
AB  - Although technology has triumphed in facilitating routine genome sequencing, new
      challenges have been created for the data-analyst. Genome-scale surveys of human
      variation generate volumes of data that far exceed capabilities for laboratory
      characterization. By incorporating functional annotations as predictors,
      statistical learning has been widely investigated for prioritizing genetic
      variants likely to be associated with complex disease. We compared three
      published prioritization procedures, which use different statistical learning
      algorithms and different predictors with regard to the quantity, type and coding.
      We also explored different combinations of algorithm and annotation set. As an
      application, we tested which methodology performed best for prioritizing variants
      using data from a large schizophrenia meta-analysis by the Psychiatric Genomics
      Consortium. Results suggest that all methods have considerable (and similar)
      predictive accuracies (AUCs 0.64-0.71) in test set data, but there is more
      variability in the application to the schizophrenia GWAS. In conclusion, a
      variety of algorithms and annotations seem to have a similar potential to
      effectively enrich true risk variants in genome-scale datasets, however none
      offer more than incremental improvement in prediction. We discuss how methods
      might be evolved for risk variant prediction to address the impending bottleneck
      of the new generation of genome re-sequencing studies. 

PMID- 26300221
TI  - Environmental enrichment does not reverse the effects of maternal deprivation on
      NMDAR and Balb/c mice behaviors.
AB  - Early adverse life experiences have been associated with anxiety-like behavior
      and memory impairment. N-methyl-d-aspartate receptors (NMDARs) play an important
      role in brain development. Enriched environments are known to positively
      influence emotional and cognitive functions in the brain. We examined the effects
      of maternal deprivation (MD) on NMDAR subunits in the hippocampus, locomotor
      activity, anxiety behaviors, and learning-memory performance of Balb/c mice. We
      also examined whether these effects could be reversed by raising the offspring in
      an enriched environment. The mice were separated from their mothers for a single
      24h episode on postnatal day (PND) 9. The mice were weaned on day 21 and were
      housed under either standard (SE) or enriched (EE) environmental conditions.
      Emotional behaviors and cognitive processes of mice were evaluated using an open
      field (OF) test, an elevated plus maze (EPM) test, and a Morris water-maze (MWM).
      NMDAR subunits (GluN1, GluN2A, and GluN2B) mRNA expression levels in the
      hippocampus were examined by real-time PCR. In OF, MD had no effect on horizontal
      locomotor activity. MD increased anxiety-like behaviors in the EPM and decreased
      spatial learning performance in MWM; however, these effects were not reversed by
      EE. MD (in SE and EE conditions) increased GluN1, GluN2A, and GluN2B mRNA
      expressions in the hippocampus. In conclusion, MD led to the deterioration of the
      emotional and cognitive processes during adulthood. Moreover, environmental
      enrichment did not reverse the deleterious effects of the MD on emotional and
      cognitive functions and increased the NMDAR levels. 

PMID- 26300222
TI  - Changes in VGLUT2 expression and function in pain-related supraspinal regions
      correlate with the pathogenesis of neuropathic pain in a mouse spared nerve
      injury model.
AB  - Vesicular glutamate transporters (VGLUTs) control the storage and release of
      glutamate, which plays a critical role in pain processing. The VGLUT2 isoform has
      been found to be densely distributed in the nociceptive pathways in supraspinal
      regions, and VGLUT2-deficient mice exhibit an attenuation of neuropathic pain;
      these results suggest a possible involvement of VGLUT2 in neuropathic pain. To
      further examine this, we investigated the temporal changes in VGLUT2 expression
      in different brain regions as well as changes in glutamate release from thalamic
      synaptosomes in spared nerve injury (SNI) mice. We also investigated the effects
      of a VGLUT inhibitor, Chicago Sky Blue 6B (CSB6B), on pain behavior, c-Fos
      expression, and depolarization-evoked glutamate release in SNI mice. Our results
      showed a significant elevation of VGLUT2 expression up to postoperative day 1 in
      the thalamus, periaqueductal gray, and amygdala, followed by a return to control
      levels. Consistent with the changes in VGLUT2 expression, SNI enhanced
      depolarization-induced glutamate release from thalamic synaptosomes, while CSB6B
      treatment produced a concentration-dependent inhibition of glutamate release.
      Moreover, intracerebroventricular administration of CSB6B, at a dose that did not
      affect motor function, attenuated mechanical allodynia and c-Fos up-regulation in
      pain-related brain areas during the early stages of neuropathic pain development.
      These results demonstrate that changes in the expression of supraspinal VGLUT2
      may be a new mechanism relevant to the induction of neuropathic pain after nerve
      injury that acts through an aggravation of glutamate imbalance. 

PMID- 26300223
TI  - Evolution of the surface state in Bi2Se2Te thin films during phase transition.
AB  - Topological insulators, a new quantum state of matter, have created exciting
      opportunities for studies in topological quantum physics and for exploring
      spintronics applications due to their gapless helical metallic surface states. In
      this study, thin films composed of alternate layers of Bi and Se (Te) ({Bi(3
      A)Te(9 A)}n/{Bi(3 A)Se(9 A)}n) were fabricated by controlling the layer thickness
      within the atomic scale using thermal evaporation techniques. The high-purity
      growth of uniform Bi2Se2Te1 thin films has not yet been achieved using a thermal
      evaporation method. However, as a result of a self-ordering process during
      annealing, an as-grown amorphous film with p-type polarity could transform into
      single crystalline Bi2Se2Te1 with n-type polarity. Using THz-time domain
      spectroscopy (THz-TDS) and ultraviolet photoemission spectroscopy (UPS), we
      concluded that the conductivity is dominated by the Drude contribution,
      suggesting the presence of a quantum well state and surface states. Moreover we
      demonstrated that the emission of terahertz waves from the (001) surface of the
      single crystalline Bi2Se2Te1 thin film would be possible under the excitation of
      790 nm femtosecond optical pulses, indicating the presence of a Dirac-fermion, a
      photo-Dember effect at the surface state and the transient current within the
      surface depletion region. The results reported herein provide useful information
      regarding a valuable deposition method that can be useful in studies of the
      evolution of surface state electrons in topological insulators. 

PMID- 26300224
TI  - Pharmacological Modulation of Photoreceptor Outer Segment Degradation in a Human
      iPS Cell Model of Inherited Macular Degeneration.
AB  - Degradation of photoreceptor outer segments (POS) by retinal pigment epithelium
      (RPE) is essential for vision, and studies have implicated altered POS processing
      in the pathogenesis of some retinal degenerative diseases. Consistent with this
      concept, a recently established hiPSC-RPE model of inherited macular
      degeneration, Best disease (BD), displayed reduced rates of POS breakdown. Herein
      we utilized this model to determine (i) if disturbances in protein degradation
      pathways are associated with delayed POS digestion and (ii) whether such
      defect(s) can be pharmacologically targeted. We found that BD hiPSC-RPE cultures
      possessed increased protein oxidation, decreased free-ubiquitin levels, and
      altered rates of exosome secretion, consistent with altered POS processing.
      Application of valproic acid (VPA) with or without rapamycin increased rates of
      POS degradation in our model, whereas application of bafilomycin-A1 decreased
      such rates. Importantly, the negative effect of bafilomycin-A1 could be fully
      reversed by VPA. The utility of hiPSC-RPE for VPA testing was further evident
      following examination of its efficacy and metabolism in a complementary canine
      disease model. Our findings suggest that disturbances in protein degradation
      pathways contribute to the POS processing defect observed in BD hiPSC-RPE, which
      can be manipulated pharmacologically. These results have therapeutic implications
      for BD and perhaps other maculopathies. 

PMID- 26300226
TI  - beta-Blocker withdrawal is preferable for accurate interpretation of the
      aldosterone-renin ratio in chronically treated hypertension.
AB  - OBJECTIVES: To evaluate the effects of beta-adrenoreceptor antagonists (beta
      blockers) on the aldosterone-renin ratio (ARR) in the context of antihypertensive
      polypharmacy in chronic hypertension. To determine the optimal duration of beta
      blocker withdrawal required to normalize the ARR. DESIGN: A prospective,
      longitudinal study design was employed investigating two groups whom either
      remained on or withdrew from beta-blocker therapy. METHODS: Hypertensive
      individuals taking beta-blockers and a combination of thiazide diuretics, alpha1
      blockers, calcium channel antagonists and angiotensin-converting enzyme
      inhibitor/angiotensin receptor blocker were recruited and followed over 10-12
      weeks. beta-Blockers were withdrawn at the first visit. Blood pressure (BP) was
      measured at each visit and blood drawn serially for measurement of plasma renin
      activity (PRA), direct renin concentration (DRC) and aldosterone. BP was
      optimized by maximizing non-renin-suppressing antihypertensives. Main outcomes
      were ARR, DRC, PRA and aldosterone. Plasma renin activity was calculated from
      angiotensin I measured using radioimmunoassay (RIA), DRC was measured using
      chemiluminescent immunoassay assay, and aldosterone was measured using both RIA
      and Chemilluminescence Assay (CIL). RESULTS: False-positive ARR for primary
      aldosteronism (PA) occurred in 31% of patients taking beta-blockers. ARR returned
      to normal following beta-blocker withdrawal resulting from an increase in the DRC
      and PRA without affecting aldosterone. The optimum time for beta-blocker
      withdrawal was 2 weeks when using DRC and 3 weeks for PRA. beta-Blocker
      withdrawal did not adversely affect blood pressure. CONCLUSION: Raised ARR
      consequent to beta-blocker therapy causes false-positive screening for PA. Where
      beta-blockers can be safely withdrawn, this effect is reversed within 2-3 weeks
      depending on whether DRC or PRA is used to calculate ARR.

PMID- 26300225
TI  - Beta-adrenergic receptor mediated inflammation control by monocytes is associated
      with blood pressure and risk factors for cardiovascular disease.
AB  - Overwhelming data indicate that individuals with even mildly elevated blood
      pressure (BP) are at great risk for developing clinical hypertension and future
      cardiovascular disease (CVD). There remains a lack of consensus regarding
      treatment strategies for mildly elevated BP, termed prehypertension, and the
      knowledge of pathophysiology and mechanisms of its clinical outcomes remains
      limited. Our primary aim was to investigate betaAR-mediated inflammation control
      (BARIC) responses of blood monocytes to isoproterenol (Iso) in relation to BP and
      CVD risk factors, including obesity, depressive mood, fasting glucose,
      triglycerides, and cholesterol levels in the 64 prehypertensive compared to 84
      individuals with normal BP. BARIC was determined by measuring the degree of
      inhibition in lipopolysaccharides-stimulated monocytic intracellular TNF
      production by ex vivo Iso treatment (10(-8)M). Depressive mood was assessed by
      Beck Depression Inventory (BDI). Fasting metabolic and lipid panels were
      assessed, and plasma levels of inflammatory cytokines TNF, IL-1beta, IL-6 were
      measured in a subset to confirm proinflammatory state of prehypertensive
      participants. Prehypertensive participants were older, heavier, included more
      men, and presented higher levels of fasting glucose, triglycerides, cholesterol,
      and plasma TNF compared to normotensive participants (p's<.05). BARIC was
      significantly attenuated in the prehypertensive compared to normotensive group
      (p<.05). BARIC was negatively associated with systolic BP, diastolic BP, age,
      BMI, fasting glucose, triglycerides, total and low density cholesterol levels,
      and somatic depressive symptoms in all participants (p's<.0001 to .05). However,
      among the prehypertensive individuals BARIC was positively associated with SBP
      even after controlling for the covariates (age, gender, race, BMI, glucose and
      lipid panel, somatic BDI scores) (p<.05). This differing nature of the BARIC-SBP
      relationship between the two BP groups may be attributed to moderating factors
      such as cardiorespiratory fitness or depressive symptoms that could not be
      clearly deciphered in this current study. Nonetheless, our findings indicate the
      associations between inflammation dysregulation mediated by sympathoadrenal
      activation and BP that is observable even among individuals with normal to mildly
      elevated BP. BARIC may be a useful and sensitive indicator of elevated risk for
      vascular inflammatory disease that can be detected even at lower BP levels,
      especially given its associations with traditional CVD risk factors and the
      critical role of monocytes in atherogenic processes. 

PMID- 26300227
TI  - Polyphenolic composition of grape stem extracts affects antioxidant activity in
      endothelial and muscle cells.
AB  - The aim of the present study was the assessment of the antioxidant effects of
      polyphenolic extracts derived from the stems of three Greek grape varieties
      (Moshomayro, Mavrotragano and Mandilaria) in endothelial (EA.hy926) and muscle
      (C2C12) cells. We also investigated the effects of the polyphenolic composition
      on the antioxidant effects of the grape stem extracts. For this purpose, the
      endothelial and muscle cells were treated with low non-cytotoxic concentrations
      of the extracts for 24 h in order to assess the effects of the extracts on
      cellular redox status using oxidative stress biomarkers. The oxidative stress
      markers were thiobarbituric acid reactive substances (TBARS), protein carbonyl
      (CARB) levels, reactive oxygen species (ROS) levels and glutathione (GSH) levels.
      The results revealed that treatment of the EA.hy926 cells with Mandilaria extract
      significantly decreased the TBARS levels by 14.8% and the CARB levels by 25.9 %,
      while it increased the GSH levels by 15.8% compared to the controls. Moreover,
      treatment of the EA.hy926 cells with Mavrotragano extract significantly increased
      the GSH levels by 20.2%, while it significantly decreased the TBARS and CARB
      levels by 12.5% and 16.6%, respectively. Treatment of the C2C12 cells with
      Mandilaria extract significantly decreased the TBARS levels by 47.3 %, the CARB
      levels by 39.0 % and the ROS levels by 21.8%, while it increased the GSH levels
      by 22.6% compared to the controls. Moreover, treatment of the C2C12 cells with
      Mavrotragano significantly decreased the TBARS, CARB and ROS levels by 36.2%,
      35.9% and 16.5%, respectively. In conclusion, to the best of our knowledgel, our
      results demonstrate for the first time that treatment with grape stem extracts at
      low concentrations improves the redox status of endothelial and muscle cells.
      Thus, grape stem extracts may be used for developing antioxidant food supplements
      or biofunctional foods. However, it was also found that the polyphenolic
      composition of grape stem extracts affects their antioxidant capacity. For
      example, the results suggested that trans-resveratrol, gallic acid, (+)-catechin,
      ferulic acid, caffeic acid, quercetin, coumaric acid and kaempferol may be
      essential for the antioxidant activity of grape stem extracts.

PMID- 26300228
TI  - Mammary Stem Cells and Tumor-Initiating Cells Are More Resistant to Apoptosis and
      Exhibit Increased DNA Repair Activity in Response to DNA Damage.
AB  - Adult stem cells and tumor-initiating cells (TICs) often employ different
      mechanisms of DNA damage response (DDR) as compared to other tissue cell types.
      However, little is known about how mammary stem cells (MaSCs) and mammary TICs
      respond to DNA damage. Using the mouse mammary gland and syngeneic p53-null
      tumors as models, we investigated the molecular and physiological consequences of
      DNA damage in wild-type MaSCs, p53-null MaSCs, and p53-null TICs. We showed that
      wild-type MaSCs and basal cells are more resistant to apoptosis and exhibit
      increased non-homologous end joining (NHEJ) activity. Loss of p53 in mammary
      epithelium affected both cell-cycle regulation and DNA repair efficiency. In p53
      null tumors, we showed that TICs are more resistant to ionizing radiation (IR)
      due to decreased apoptosis, elevated NHEJ activity, and more-rapid DNA repair.
      These results have important implications for understanding DDR mechanisms
      involved in both tumorigenesis and therapy resistance. 

PMID- 26300229
TI  - Polyphenolic composition and antioxidant activity of the under-utilised Prunus
      mahaleb L. fruit.
AB  - BACKGROUND: The identification of novel plant-based functional foods or
      nutraceutical ingredients that possess bioactive properties with antioxidant
      function has recently become important to the food, nutraceutical and cosmetic
      industries. This study evaluates the polyphenolic composition, identifies
      bioactive compounds and assays the total antioxidant capacity of Prunus mahaleb
      L. fruits collected from different populations and sampling years in the
      countryside around Bari (Apulia Region, Italy). RESULTS: We identified nine
      polyphenolic compounds including major anthocyanins, coumaric acid derivatives
      and flavonols from P. mahaleb fruits. The anthocyanin content (in some
      populations > 5 g kg(-1) fresh weight; FW) in the fruit was comparable to that
      reported for so-called superfruits such as bilberries, chokeberries and
      blackcurrants. Coumaric acid derivatives comprised a large portion of the total
      polyphenolic content in the P. mahaleb fruits. Antioxidant activities, assessed
      using ORAC and TEAC assays, measured up to 150 and 45 mmol Trolox equivalents kg(
      1) FW, respectively. Therefore antioxidant capacity of P. mahaleb fruits is
      relatively high and comparable to that of superfruit varieties that are often
      used in commercial nutraceutical products. CONCLUSION: Our findings suggest that
      mahaleb fruit (currently not consumed fresh or used in other ways) could serve as
      a source of bioactive compounds and therefore find interest from the functional
      food and nutraceutical industries, as a natural food colorant and antioxidant
      ingredient in the formulation of functional foods. (c) 2015 Society of Chemical
      Industry.

PMID- 26300230
TI  - Reply to letter to the editor.

PMID- 26300231
TI  - Differences in Handwritings of Schizophrenia Patients and Examination of the
      Change after Treatment.
AB  - The aim of this study was to analyze the differences between the handwritings of
      schizophrenia patients and healthy subjects in addition to the changes that
      occurred in schizophrenia patients' handwriting in response to the treatment. The
      test subjects were 29 schizophrenia patients and 29 healthy individuals with the
      same age, gender, and dominant hand. The changes in the handwritings were
      examined according to 14 different parameters. On the day of admittance, the
      percentage of extra letters was 16.7%, and after 7-10 days of hospitalization, it
      rose to 33.3%. The percentage of skipped words decreased from 29.2% to 16.7%
      after 7-10 days of hospitalization, and to 10% after 3 weeks. The letters written
      by schizophrenia patients are significantly larger in height and width compared
      to the control group. The schizophrenia patients showed a higher incidence of
      crossed-out letters, adding extra words, missing punctuation as well as missing
      words.

PMID- 26300232
TI  - The Relationship between Intraoperative Rupture and Recurrence of Pediatric
      Ovarian Neoplasms: Preliminary Observations.
AB  - STUDY OBJECTIVE: We investigated whether rupture increased the recurrence rate of
      pediatric ovarian neoplasms. DESIGN: 20-year single-institution retrospective
      study. SETTING: Tertiary, free-standing, university children's hospital.
      PARTICIPANTS: All girls with ovarian neoplasms treated during between 1991 and
      2011. MAIN OUTCOME MEASURE: Tumor recurrence. RESULTS: Fifty-nine tumors in 53
      patients were managed, including 51/59 (86%) benign and 8/59 (14%) malignant.
      Laparotomy was employed in 44/59 (75%), laparoscopy in 8/59 (14%), and
      laparoscopy converted to laparotomy in 7/59 (12%). Total and partial oophorectomy
      (cystectomy) was used for 15/51 (29%) and 36/51 (71%) of benign tumors,
      respectively. All malignant tumors underwent total oophorectomy. Accidental
      rupture or intentional tumor puncture occurred in 26/56 cases (46%), 23/51 benign
      and 3/5 malignant. Rupture was associated with increasing cyst size on univariate
      and multivariate analyses (p = 0.002 and p = 0.004, respectively). There were 5
      recurrences (9%) in 4 patients, including 4 benign (3 mature teratomas, 1
      mucinous cystadenoma), and 1 malignant yolk sac tumor. Recurrence occurred in
      2/30 (7%) without rupture and 3/26 (12%) with rupture, p = 0.66. Follow-up was
      available for 50/53 patients (94%), with a median of 23.8 months [range 0.2-189
      months]. All recurrences were salvaged by surgery. CONCLUSIONS: In this limited
      study, intra-operative rupture did not increase the recurrence rate or worsen the
      prognosis of pediatric ovarian neoplasms.

PMID- 26300233
TI  - Human Papillomavirus Vaccine: Continuation, Completion, and Missed Opportunities.
AB  - STUDY OBJECTIVE: To examine human papillomavirus (HPV) series completion in older
      adolescents and assess vaccination completion opportunities missed by providers.
      DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES:
      Electronic medical records were queried for women 18-24 years old who initiated
      the HPV vaccine in the Adolescent Medicine, Young Mother's, or Family Planning
      clinics at Children's Hospital Colorado from January 1, 2010-December 31, 2012.
      Clinic visits during appropriate dosing intervals of HPV vaccine at which the
      second (4-14 weeks after first dose) or third (21-40 weeks after first dose and
      >12 weeks after second dose) doses were not administered were counted as "missed
      opportunities." RESULTS: A total of 1072 female adolescents initiated the HPV
      series during the study period; 20.9% completed the series within 1 year. Of
      these, 33.7% who did not receive their second dose had at least 1 missed
      opportunity and 25.5% who received the second but not the third had a missed
      opportunity. Women who initiated the vaccine in the Family Planning clinic were
      less likely to have missed opportunities than those in other adolescent clinics
      (36.2% vs 56.4%; P < .001). CONCLUSION: A significant number of female
      adolescents who initiated the HPV vaccine attended clinic visits at which
      opportunities for vaccine continuation and completion were missed. This
      emphasizes the importance of provider awareness of vaccine updates at every
      adolescent visit. Our overall completion rate is significantly lower than
      published rates and might reflect older adolescents' inexperience in managing
      their own preventive health care. Our results clearly identify the need for
      provider and patient interventions to improve vaccine series completion.

PMID- 26300235
TI  - The efficacy and safety of prehospital therapeutic hypothermia in patients with
      out-of-hospital cardiac arrest: A systematic review and meta-analysis.
AB  - BACKGROUND: The benefit of therapeutic hypothermia (TH) to patients suffering out
      of-hospital cardiac arrest (OHCA) has been well established. However, the effect
      of prehospital cooling remains unclear. We aimed to investigate the efficacy and
      safety of prehospital TH for OHCA patients by conducting a systematic review of
      randomised controlled trials (RCTs). METHODS: The MEDLINE, EMbase and CENTRAL
      databases were searched for publications from inception to April 2015. RCTs that
      compared cooling with no cooling in a prehospital setting among adults with OHCA
      were eligible for inclusion. Random- and fixed-effect models were used depending
      on inter-study heterogeneity. RESULTS: Eight trials that recruited 2379
      participants met the inclusion criteria. Prehospital TH was significantly
      associated with a lower temperature at admission (mean difference (MD) -0.94; 95%
      confidence interval (CI) -1.06 to -0.82). However, survival upon admission (Risk
      ratio (RR) 1.01, 95%CI 0.98-1.04), survival at discharge (RR 1.02, 95%CI 0.91
      1.14), in-hospital survival (RR 1.05, 95%CI 0.92-1.19) and good neurological
      function recovery (RR 1.06, 95% CI 0.91-1.23) did not differ between the TH
      treated and non-treated groups. Prehospital cooling increased the incidence of
      recurrent arrest (RR 1.23, 95%CI 1.02-1.48) and decreased the PH at admission (MD
      -0.04, 95%CI -0.07 to -0.02). Pulmonary oedema did not differ between the arms
      (RR 1.02, 95%CI 0.67-1.57). None of the potentially controversial issues (cooling
      methods, time of inducing TH, the proportion of continuing cooling in hospital,
      actual prehospital infusion volume and primary cardiac rhythms) affected the
      efficacy. CONCLUSION: Evidence does not support the administration of prehospital
      TH to patients with OHCA.

PMID- 26300234
TI  - The effect of resuscitation in 100% oxygen on brain injury in a newborn rat model
      of severe hypoxic-ischaemic encephalopathy.
AB  - AIM: Infants with birth asphyxia frequently require resuscitation. Current
      guidance is to start newborn resuscitation in 21% oxygen. However, infants with
      severe hypoxia-ischaemia may require prolonged resuscitation with oxygen. To
      date, no study has looked at the effect of resuscitation in 100% oxygen following
      a severe hypoxic-ischaemic insult. METHODS: Postnatal day 7 Wistar rats underwent
      a severe hypoxic-ischaemic insult (modified Vannucci unilateral brain injury
      model) followed by immediate resuscitation in either 21% or 100% oxygen for 30
      min. Seven days following the insult, negative geotaxis testing was performed in
      survivors, and the brains were harvested. Relative ipsilateral cortical and
      hippocampal area loss was assessed histologically. RESULTS: Total area loss in
      the affected hemisphere and area loss within the hippocampus did not
      significantly differ between the two groups. The same results were seen for short
      term neurological assessment. No difference was seen in weight gain between pups
      resuscitated in 21% and 100% oxygen. CONCLUSION: Resuscitation in 100% oxygen
      does not cause a deleterious effect on brain injury following a severe hypoxic
      ischaemic insult in a rat model of hypoxia-ischaemia. Further work investigating
      the effects of resuscitation in 100% oxygen is warranted, especially for newborn
      infants with severe hypoxic-ischaemic encephalopathy.

PMID- 26300237
TI  - Co-existence of insulin resistance and high concentrations of circulating
      oxidized LDL lipids.
AB  - INTRODUCTION: Insulin metabolism has been previously linked to oxidized low
      density lipoproteins (ox-LDL), but corroborating intervention studies are
      lacking. We investigated whether changes in ox-LDL levels are accompanied by
      changes in insulin sensitivity in a 32-month life-style intervention study.
      MATERIALS AND METHODS: A 2-month weight reduction was followed by 6-month diet
      and exercise counselling and a 2-year follow-up period. Men of 35-50 years of
      age, BMI >= 30 kg/m(2), and waist circumference > 100 cm were recruited via
      newspapers in the city of Tampere, Finland. Of the 90 men meeting the inclusion
      criteria, 67 (76%) completed the study. Ox-LDL was estimated as the presence of
      oxidized lipids in LDL. Homeostasis model assessment of insulin resistance (HOMA
      IR), ox-LDL, and ratio of ox-LDL and high-density lipoprotein cholesterol (ox
      LDL/HDL-c) were used as the main outcome measures. RESULTS: The detected changes
      in HOMA-IR were strikingly similar to those in ox-LDL and ox-LDL/HDL-c. Compared
      to the first HOMA-IR quartile, the fourth quartile had 23%-51% higher
      concentrations in ox-LDL and ox-LDL/HDL-c at all time points (P < 0.05 for all).
      CONCLUSION: This weight reduction intervention study adds evidence to support the
      connection between insulin metabolism and oxidized LDL, possibly contributing to
      the higher incidence of atherosclerotic cardiovascular diseases among diabetic
      patients.

PMID- 26300236
TI  - Cardiac Dysfunction in HIV-1 Transgenic Mouse: Role of Stress and BAG3.
AB  - Since highly active antiretroviral therapy improved long-term survival of
      acquired immunodeficiency syndrome (AIDS) patients, AIDS cardiomyopathy has
      become an increasingly relevant clinical problem. We used human immunodeficiency
      virus (HIV)-1 transgenic (Tg26) mouse to explore molecular mechanisms of AIDS
      cardiomyopathy. Tg26 mice had significantly lower left ventricular (LV) mass and
      smaller end-diastolic and end-systolic LV volumes. Under basal conditions,
      cardiac contractility and relaxation and single myocyte contraction dynamics were
      not different between wild-type (WT) and Tg26 mice. Ten days after open heart
      surgery, contractility and relaxation remained significantly depressed in Tg26
      hearts, suggesting that Tg26 mice did not tolerate surgical stress well. To
      simulate heart failure in which expression of Bcl2-associated athanogene 3 (BAG3)
      is reduced, we down-regulated BAG3 by small hairpin ribonucleic acid in WT and
      Tg26 hearts. BAG3 down-regulation significantly reduced contractility in Tg26
      hearts. BAG3 overexpression rescued contractile abnormalities in myocytes
      expressing the HIV-1 protein Tat. We conclude: (i) Tg26 mice exhibit normal
      contractile function at baseline; (ii) Tg26 mice do not tolerate surgical stress
      well; (iii) BAG3 down-regulation exacerbated cardiac dysfunction in Tg26 mice;
      (iv) BAG3 overexpression rescued contractile abnormalities in myocytes expressing
      HIV-1 protein Tat; and (v) BAG3 may occupy a role in pathogenesis of AIDS
      cardiomyopathy. 

PMID- 26300238
TI  - Activation of CO2 by ionic liquid EMIM-BF4 in the electrochemical system: a
      theoretical study.
AB  - The electrochemical reduction of CO2 to CO by an ionic liquid EMIM-BF4 is one of
      the most promising CO2 reduction processes proposed so far with its high Faradaic
      efficiency and low overpotential. However, the details of the reaction mechanism
      are still unknown due to the absence of fundamental understandings. In this
      study, the most probable and stable geometries of EMIM-BF4 and CO2 were
      calculated by quantum chemistry in combination with exhaustive search. A possible
      reaction pathway from CO2 to CO catalyzed by EMIM-BF4, including the most
      plausible intermediates and the corresponding transition states, was proposed.
      The role of EMIM-BF4 is explained as forming a complex of [EMIM-COOH](-) with CO2
      followed by decomposing to CO. 

PMID- 26300239
TI  - Identification of clinically relevant Corynebacterium strains by Api Coryne,
      MALDI-TOF-mass spectrometry and molecular approaches.
AB  - We evaluated the Bruker Biotyper matrix-assisted laser desorption ionization-time
      of flight (MALDI-TOF) mass spectrometry (MS) for the identification of 97
      Corynebacterium clinical in comparison to identification strains by Api Coryne
      and MALDI-TOF-MS using 16S rRNA gene and hypervariable region of rpoB genes
      sequencing as a reference method. C. striatum was the predominant species
      isolated followed by C. amycolatum. There was an agreement between Api Coryne
      strips and MALDI-TOF-MS identification in 88.65% of cases. MALDI-TOF-MS was
      unable to differentiate C. aurimucosum from C. minutissimum and C. minutissimum
      from C. singulare but reliably identify 92 of 97 (94.84%) strains. Two strains
      remained incompletely identified to the species level by MALDI-TOF-MS and
      molecular approaches. They belonged to Cellulomonas and Pseudoclavibacter genus.
      In conclusion, MALDI-TOF-MS is a rapid and reliable method for the identification
      of Corynebacterium species. However, some limits have been noted and have to be
      resolved by the application of molecular methods. 

PMID- 26300240
TI  - Autologous hematopoietic stem cell transplantation reverses skin fibrosis but
      does not change skin vessel density in patients with systemic sclerosis.
AB  - Hematopoetic stem cell transplantation (HSCT) improves survival in patients with
      severe systemic sclerosis (SSc) by resetting the immune system. We studied how
      HSCT acts on the key SSc skin pathology findings (fibrosis and vascularization).
      In mean, 3 skin punch biopsies per patient (range 2-6) were analyzed from 13
      patients (5 females) with severe diffuse SSc before and up to 96 months after
      HSCT. Fibrosis of the four skin layers was graded semi-quantitatively and an
      overall fibrosis score was then calculated. Vessel numbers and calibers were
      assessed in the superficial and deeper dermis after immune-staining for
      endothelial antigens (CD31, VE-cadherin and vWF). The median age of patients at
      HSCT was 47 (24-64) years. The overall median modified Rodnan skin score
      decreased from 24 to 10 (P=0.003) at first follow-up within a median of 9 (6-36)
      months after HSCT as did the histological skin score (P=0.03). The modified
      Rodnan skin score and the fibrosis score correlated positively (r=0.589,
      P<0.001). The vessels density did not significantly change after HSCT nor did the
      expression of the tested endothelial markers. Although improving skin fibrosis in
      patients with SSc, HSCT does not alter vessel density within skin biopsies. 

PMID- 26300241
TI  - What common biomarkers characterize a triple-negative profile in breast cancer?
AB  - Triple-negative breast cancers are not a homogeneous subgroup. There is
      substantial intra-subgroup diversity in tumor biology, prognosis and treatment
      sensitivity. Then, these triple-negative phenotype (TNP) groups, having specific
      features, can be again divided into subclasses based on an added
      immunohistochemical markers. The challenge in treating TNP breast cancers is that
      they are not responsive to antiestrogens or trastuzumab secondary to negative
      receptor status, and as a result have a poor prognosis. Therefore, the presence
      or absence of supplementary markers could help predict which therapies are best
      suited for patients based on the pattern that their disease markers show. In this
      review, we will recapitulate the major supplementary biomarkers related to triple
      negative breast cancer, which could give new therapeutic options. 

PMID- 26300243
TI  - Intraosseous access in neonates and infants: risk of severe complications - a
      case report.
AB  - Gaining vascular access in a neonate during cardiopulmonary resuscitation is
      crucial and challenging. Intraosseous (IO) access can offer a fast and reliable
      method for achieving emergency access for fluids and drugs when venous access
      fails in a critically ill child. IO access can however result in rare, but
      serious adverse events including compartment syndrome and amputation. We describe
      a case resulting in leg amputation due to IO infusion in a neonate after
      resuscitation and therapeutic hypothermia. We compared 10 tibia X-rays in three
      age groups. The mean medullary diameter of the proximal tibia at the recommended
      site for IO access was 7 mm in neonate, 10 mm in 1- to 12-month-old infants, and
      12 mm in 3- to 4-year-old children. This provides a narrow margin of safety for
      the correct positioning and the avoidance of dislodgement of the IO needle. The
      correct position of the IO needle should be confirmed by bone marrow aspiration
      and fluid bolus. Unnecessary touching of the IO needle after fixing it in place
      should be avoided by inserting a luer-lock catheter with a three-way stop-cock
      for IO drug and fluid administration. Regular observation of the circulation and
      possible swelling of the leg should be performed. The IO administration of
      inotropic infusions should also be avoided after the initial resuscitation phase.
      When treating with therapeutic hypothermia, it may be wise to remove the IO
      needle much earlier than the currently recommended 24 h because of the problems
      in peripheral circulation and its monitoring.

PMID- 26300244
TI  - Structural insights into the interaction between molluscan hemocyanins and
      phenolic substrates: An in silico study using docking and molecular dynamics.
AB  - Hemocyanin is a multimeric type-3 copper containing oxygen carrier protein that
      exhibits phenoloxidase-like activity and is found in selected species of
      arthropoda and mollusca. The phenoloxidase activity in the molluscan hemocyanins
      can be triggered by the proteolytic removal of the C-terminal beta-rich sandwich
      domain of the protein or by the treatment with chemical agents like SDS, both of
      which enable active site access to the phenolic substrates. The mechanism by
      which SDS treatment enhances active site access to the substrates is however not
      well understood in molluscan hemocyanins. Here, using a combination of in silico
      molecular dynamics (MD) and docking studies on the crystal structure of Octopus
      dofleini hemocyanin (PDB code:1JS8), we demonstrate that the C-terminal beta
      domain of the protein plays a crucial role in regulating active site access to
      bulky phenolic substrates. Furthermore, MD simulation of hemocyanin in SDS
      revealed displacement of beta-domain, enhanced active site access and a resulting
      increase in binding affinity for substrates. These observations were further
      validated by enzyme kinetics experiments. 

PMID- 26300242
TI  - Relevance of tumor-infiltrating lymphocytes in breast cancer.
AB  - While breast cancer has not been considered a cancer amenable to
      immunotherapeutic approaches, recent studies have demonstrated evidence of
      significant immune cell infiltration via tumor-infiltrating lymphocytes in a
      subset of patient tumors. In this review we present the current evidence
      highlighting the clinical relevance and utility of tumor-infiltrating lymphocytes
      in breast cancer. Retrospective and prospective studies have shown that the
      presence of tumor-infiltrating lymphocytes is a prognostic marker for higher
      responses to neoadjuvant chemotherapy and better survival, particularly in triple
      negative and HER2-positive early breast cancer. Further work is required to
      determine the immune subsets important in this response and to discover ways of
      encouraging immune infiltrate in tumor-infiltrating lymphocytes-negative
      patients. 

PMID- 26300246
TI  - Caveolin-1 and glucose transporter 4 involved in the regulation of glucose
      deprivation stress in PC12 cells.
AB  - Recent evidence suggests that caveolin-1 (Cav-1), the major protein constituent
      of caveolae, plays a prominent role in neuronal nutritional availability with
      cellular fate regulation besides in several cellular processes such as
      cholesterol homeostasis, regulation of signal transduction, integrin signaling
      and cell growth. Here, we aimed to investigate the function of Cav-1 and glucose
      transporter 4 (GLUT4) upon glucose deprivation (GD) in PC12 cells. The results
      demonstrated firstly that both Cav-1 and GLUT4 were up-regulated by glucose
      withdrawal in PC12 cells by using Western blot and laser confocal technology.
      Also, we found that the cell death rate, mitochondrial membrane potential (MMP)
      and intracellular free Ca(2+) concentration ([Ca(2+)]i) were also respectively
      changed followed the GD stress tested by CCK8 and flow cytometry. After knocking
      down of Cav-1 in the cells by siRNA, the level of [Ca(2+)]i was increased, and
      MMP was reduced further in GD-treated PC12 cells. Knockdown of Cav-1 or
      methylated-beta-Cyclodextrin (M-beta-CD) treatment inhibited the expression of
      GLUT4 protein upon GD. Additionally, we found that GLUT4 could translocate from
      cytoplasm to cell membrane upon GD. These findings might suggest a
      neuroprotective role for Cav-1, through coordination of GLUT4 in GD. 

PMID- 26300245
TI  - Estimation of exposure to atmospheric pollutants during pregnancy integrating
      space-time activity and indoor air levels: Does it make a difference?
AB  - Studies of air pollution effects during pregnancy generally only consider
      exposure in the outdoor air at the home address. We aimed to compare exposure
      models differing in their ability to account for the spatial resolution of
      pollutants, space-time activity and indoor air pollution levels. We recruited 40
      pregnant women in the Grenoble urban area, France, who carried a Global
      Positioning System (GPS) during up to 3 weeks; in a subgroup, indoor measurements
      of fine particles (PM2.5) were conducted at home (n=9) and personal exposure to
      nitrogen dioxide (NO2) was assessed using passive air samplers (n=10). Outdoor
      concentrations of NO2, and PM2.5 were estimated from a dispersion model with a
      fine spatial resolution. Women spent on average 16 h per day at home. Considering
      only outdoor levels, for estimates at the home address, the correlation between
      the estimate using the nearest background air monitoring station and the estimate
      from the dispersion model was high (r=0.93) for PM2.5 and moderate (r=0.67) for
      NO2. The model incorporating clean GPS data was less correlated with the estimate
      relying on raw GPS data (r=0.77) than the model ignoring space-time activity
      (r=0.93). PM2.5 outdoor levels were not to moderately correlated with estimates
      from the model incorporating indoor measurements and space-time activity (r=-0.10
      to 0.47), while NO2 personal levels were not correlated with outdoor levels (r=
      0.42 to 0.03). In this urban area, accounting for space-time activity little
      influenced exposure estimates; in a subgroup of subjects (n=9), incorporating
      indoor pollution levels seemed to strongly modify them.

PMID- 26300247
TI  - [Microenvironments induce iPSCs and BMSCs into neuron-like cells--Reelin's
      regulative role in cell differentiation and polarization].
AB  - The present study was aimed to investigate how the induced pluripotent stem cells
      (iPSCs) and bone marrow mesenchymal stem cells (BMSCs) differentiate into neuron
      like cells under the induction of hippocampal microenvironments and Reelin's
      regulation. iPSCs or BMSCs were co-cultured with WT (wild type) or genotypic
      hippocampal slice and cerebral homogenate supernatant, then the stem cells'
      differentiation under the induction of hippocampal environment was observed by
      using immunofluorescence technique. In the meantime, stem cells were co-cultured
      with hippocampal slice and cerebral conditioned medium of reeler (Reelin
      deletion) mouse respectively. The results showed that both adhesive iPSCs and
      BMSCs on WT hippocampal slice exhibited lamination of double "C" shape with high
      density on granular and pyramidal layers. The stem cells could differentiate into
      neuron-like cells with obvious polarization on WT hippocampal slice. In pyramidal
      cell layer, the differentiated neuron-like cells were oriented vertically with
      similar shapes of pyramidal cell in vivo, and the cells within molecule layer
      were arranged horizontally. In addition, adhesive iPSCs and BMSCs could
      differentiate into Nestin positive neural stem cells and NeuN positive neurons,
      respectively, under WT hippocampal microenvironment. On the other hand, under
      induction of hippocampal microenvironment of reeler mouse, iPSCs and BMSCs
      differentiation could also be seen, but their lamination was in disorder, and
      cell polarization was irregular. Moreover, differentiation and polarization of
      the iPSCs and BMSCs were delayed. These results suggest both iPSCs and BMSCs can
      differentiate into neuron-like cells under the induction of hippocampal
      microenvironments. Reelin is involved in the regulation of neuronal
      differentiation and cell polarization. Without Reelin, the cellular lamination
      and polarization appear irregular, and the stem cells' differentiation is
      delayed. 

PMID- 26300248
TI  - [In vitro whole-cell patch clamp recordings of neurons in subnuclei of mouse
      inferior colliculus].
AB  - The inferior colliculus (IC) is a pivot along the central auditory pathway. Using
      infrared visual whole-cell patch clamp recording technique, we investigated the
      electrophysiological properties of IC subnuclei neurons. Recordings were made
      from 88 neurons, including 21 neurons from the dorsal cortex of the IC (ICd), 43
      neurons from the central nucleus of the IC (ICc) and 24 neurons from the external
      cortex of the IC (ICx). Based on the responses to positive current injection,
      three firing patterns, i.e., onset (6.8%, n = 6), adapting (39.8%, n = 35) and
      sustained (53.4%, n = 47) patterns, were identified. The hyperpolarization
      activated inward current (Ih) could be recorded in half of the neurons (49/88).
      The sustained pattern occurred in more than half of ICd and ICc neurons (61.9%
      and 67.4%), while the adapting pattern occurred in majority of ICx neurons (75%).
      Action potential (AP) threshold and time constant also showed significant
      differences across neurons from the ICd, the ICc and the ICx. Our results
      indicate that IC neurons are different in electrophysiological properties across
      the subnuclei. The variance of the responses may be related to the distinct types
      of neurons as well as the received projections, which is implicated in the
      distinct roles of IC neurons in central auditory processing. 

PMID- 26300249
TI  - [Effect of orexin-A and orexin-1 receptor antagonist injected into the fourth
      ventricle of rats on food-intake and spontaneous physical activity].
AB  - The present study was aimed to investigate the effects of orexin-A and orexin-1
      receptor (OX1R) antagonist injected into the fourth ventricle of rats on food
      intake and spontaneous physical activity (SPA). Obese rat model was induced by
      high fat diet. Different doses of orexin-A or SB334867, an OX1R antagonist, were
      injected into the fourth ventricle of obese and normal rats respectively. SPA and
      food intake were monitored for 4 h after injection in both light and dark
      environment. In the light measurement cycle, different doses of orexin-A
      significantly stimulated feeding and SPA in all injected rats, and the animals'
      responses showed a dose-dependent manner (P < 0.05-0.01), and compared with those
      of normal rats, the orexin-A induced food intake and SPA were more pronounced in
      obese rats. In the dark measurement cycle, different doses of orexin-A had no
      obvious effect on food intake and SPA in both normal and obese rats (P > 0.05).
      In the light cycle, different doses of SB334867 significantly decreased food
      intake and SPA in all rats during 0-2 h and 2-4 h after injection (P < 0.05), but
      the food intake and SPA in obese rats were significantly greater than those of
      normal rats. In the dark cycle, different doses of SB334867 showed no obvious
      effect on food intake and SPA of normal and obese rats (P > 0.05). These results
      suggest that fourth cerebral ventricle nuclei may be one target for orexin-A and
      light condition may play an important role in orexin-A and OX1R physiological
      functional processes.

PMID- 26300250
TI  - [Cold inducible RNA-binding protein inhibits hippocampal neuronal apoptosis under
      hypothermia by regulating redox system].
AB  - In this study, we intend to confirm our hypothesis that cold inducible RNA
      binding protein (CIRP) can inhibit neuronal apoptosis through suppressing the
      formation of oxygen free radicals under hypothermia. Primary rat hippocampal
      neurons were isolated and cultured in vitro, and were divided into five groups:
      (1) normal control group (37  degrees C), (2) cells infected by empty viral
      vector group, (3) CIRP over-expressed group, (4) CIRP knock-down group, and (5)
      hypothermia control group. Cells in groups 2-5 were cultured under 32  degrees C,
      5% CO2. Apoptosis of hippocampal neurons were detected by Annexin V-FITC/PI
      staining and flow cytometry; Expression of CIRP was determined by Western blot;
      Redox-related parameters (T-AOC, GSH-Px, SOD, MDA) were detected by ELISA kits.
      Results showed that CIRP expression levels were significantly increased (P <
      0.01) and the apoptotic rates were significantly decreased (P < 0.01) in
      hypothermia control group and CIRP over-expressed group when compared with normal
      control group. On the other hand, the apoptotic rate was significantly increased
      (P < 0.05) in CIRP knock-down group compared with that in hypothermia control
      group. The levels of redox parameters in hypothermia control group and CIRP over
      expressed group were significantly changed in comparison with those in normal
      control group, CIRP knock-down group and empty viral vector infected group,
      respectively (P < 0.05 or P < 0.01). These results suggest that up-regulation of
      CIRP by hypothermia treatment can protect the neuron from apoptosis through
      suppressing the formation of oxygen free radicals.

PMID- 26300251
TI  - CyPA-CD147-ERK1/2-cyclin D2 signaling pathway is upregulated during rat left
      ventricular hypertrophy.
AB  - The changes of serum cyclophilin A (CyPA), its receptor CD147 and the downstream
      signaling pathway during the process of cardiac hypertrophy remain unknown. The
      present study aims to investigate the relationships between CyPA-CD147-ERK1/2
      cyclin D2 signaling pathway and the development of cardiac hypertrophy. Left
      ventricular hypertrophy was prepared by 2-kidney, 2-clip in Sprague-Dawley rats
      and observed for 1 week, 4 and 8 weeks. Left ventricular hypertrophy was
      evaluated by ratio of left ventricular heart weight to body weight (LVW/BW) and
      cardiomyocyte cross sectional area (CSA). CyPA levels in serum were determined
      with a rat CyPA ELISA kit. Expressions of CyPA, CD147, phospho-ERK1/2 and cyclin
      D2 in left ventricular myocytes were determined by Western blot and
      immunostaining. Compared with sham groups, systolic blood pressure reached
      hypertensive levels at 4 weeks in 2K2C groups. LVW/BW and CSA in 2K2C groups were
      significantly increased at 4 and 8 weeks after clipping. ELISA results indicated
      a prominent increase in serum CyPA level associated with the degree of left
      ventricular hypertrophy. Western blot revealed that the expressions of CyPA,
      CD147, phospho-ERK1/2 and cyclin D2 in left ventricular tissues were also
      remarkably increased as the cardiac hypertrophy developed. The results of the
      present study demonstrates that serum CyPA and CyPA-CD147-ERK1/2-cyclin D2
      signaling pathway in ventricular tissues are time-dependently upregulated and
      activated with the process of left ventricular hypertrophy. These data suggest
      that CyPA-CD147 signaling cascade might play a role in the pathogenesis of left
      ventricular hypertrophy, and CyPA might be a prognosticator of the degree of left
      ventricular hypertrophy. 

PMID- 26300252
TI  - [Role of calcineurin in down-regulation of left ventricular transmural voltage-
      dependent K(+) currents in mice with heart failure].
AB  - The aim of the present study was to investigate the role of calcineurin in the
      down-regulation of left ventricular transmural voltage-dependent K(+) currents in
      heart failure. Transverse aorta was banded by using microsurgical techniques to
      create mouse heart failure model. Sham-operated (Sham) or aorta banded (Band)
      mice were randomized to receive calcineurin inhibitor cyclosporine A (CsA) or
      vehicle. The densities and kinetic properties of voltage-dependent K(+) currents,
      as well as action potential (AP), of left ventricular subendocardial (Endo) and
      subepicardial (Epi) myocytes were determined by using whole-cell patch-clamp
      technique. The results showed that calcineurin activity was significant higher in
      Endo myocytes than that in Epi ones in all the groups. Compared with Sham group,
      Band mice showed significantly increased calcineurin activity both in Endo and
      Epi myocytes. CsA significantly reduced calcineurin activity in Band mice. CsA
      treatment in Band mice partially reversed the down-regulation of Ito density,
      completely reversed the down-regulation of IK,slow density both in Endo and Epi
      myocytes, and Iss density in Endo myocytes. In addition, CsA treatment in Band
      mice partially antagonized the prolongation of action potential duration (APD),
      and APD at 50% (APD50) and 90% repolarization (APD90) were significantly reduced.
      Because of non-parallel shortening of APD in Endo and Epi myocytes, the ratio of
      Endo/Epi APD90 was reduced from 4.8:1 in Band mice to 2.6:1 in CsA-treated mice,
      which was close to that in Sham mice. The results suggest that non-parallel
      activation of calcineurin in Endo and Epi myocytes contributes to the down
      regulation of transmural voltage-dependent K(+) currents and the amplification of
      transmural dispersion of repolarization (TDR) in left ventricular failure hearts.
      Inhibition of calcineurin may be a potential new therapeutic strategy to prevent
      and cure arrhythmias and sudden death in heart failure. 

PMID- 26300253
TI  - [Suppression of E3 ubiquitin ligase Cbl-b in interleukin-1 signaling].
AB  - The present study aims to investigate the effect of Cbl-b, a member of E3
      ubiquitin ligase family, on interleukin-1 (IL-1) pathway in synoviocytes. The
      protein expression levels of Cbl-b and IL-1-induced matrix metalloproteinase 13
      (MMP-13) in synoviocytes were analyzed by Western blot. Collagen substrates were
      incubated with the conditioned medium collected from synoviocytes cultures and
      then subjected to SDS-PAGE for analysis of collagen degradation. The results
      showed that compared with wild-type cells, Cbl-b-deficient cells expressed more
      MMP-13 protein and had enhanced ability to degrade collagens under IL-1
      stimulation. These data suggest that Cbl-b may negatively regulate IL-1-triggered
      degradation of collagen matrix in synoviocytes. 

PMID- 26300254
TI  - [Activation of spinal MrgC receptors inhibits hyperalgesia in rats].
AB  - This study was aimed to investigate the mechanisms of the modulation effect of
      activation of spinal Mas-related gene C (MrgC) receptors on hyperalgesia induced
      by intraplantar (i.pl.) injection of (Tyr6)-gamma2-MSH-6-12 (MSH) or complete
      Freund's adjuvant (CFA). Paw withdrawal latency test and immunohistochemistry
      were used to observe the effect of intrathecal (i.t.) administration of MSH or
      BAM8-22, two selective agonists of MrgC receptor, in hyperalgesia in rats. The
      results showed that i.t. administration of MSH inhibited acute hyperalgesic
      response induced by i.pl. application of MSH, while did not change thermal
      nociceptive threshold in naive rats. The i.t. administration of MSH also
      attenuated CFA-induced inflammatory hyperalgesia. However, i.t. administration of
      the MU-opioid receptor (MOR) antagonist CTAP blocked the induction of delayed
      anti-hyperalgesia by MSH. The i.t. injection of BAM8-22 at a dose of 30 nmol
      evidently reduced the number of CFA-evoked nitric oxide synthase (NOS)-positive
      neurons and the expression of calcitonin gene-related peptide (CGRP)
      immunoreactivity positive nerve fibers at L3-L5 segments of the spinal cord.
      These results suggest that the activation of MrgC receptor in CFA-induced
      inflammation reduces inflammatory hyperalgesia through inactivation of NOS
      neurons and down-regulation of CGRP expressions, and generates delayed but long
      lasting anti-nociception through the endogenous activation of MOR via indirect
      mechanisms. Agonists for MrgC receptors may, therefore, represent a new class of
      antihyperalgesics for treating inflammatory pain because of the highly specific
      expression of their targets. 

PMID- 26300255
TI  - [Simultaneous separation of primary cardiomyocytes and cardiac fibroblasts from
      neonatal rats with density gradient centrifugation].
AB  - To improve a fast and high-quality isolation method for culturing the primary
      cardiomyocyte and fibroblast in vitro, the neonatal Wistar rats were decapitated
      accordingly and left ventricles were isolated under the sterile condition. The
      ventricles were chopped and digested in the enzyme solution containing 0.5 mg/mL
      type II collagenase. During this process, the digesting time, frequency and
      stirring speed, centrifuging frequency and speed were strictly controlled. The
      cardiomyocytes were separated from the cardiac fibroblast by using the Percoll
      density gradient centrifugation. The cell viability was tested by staining with
      0.2% trypan blue. The purity of cardiomyocytes and fibroblasts were determined by
      immunoflourescent staining with anti-cTnI, anti-Vimentin and anti-alpha-SMA
      antibodies. The results indicated that with this protocol, the viability and
      purity of cardiomyocytes were 92% and 95%. The automobile pulse of the adhered
      cardiomyocyte was visible. For fibroblasts, the cell viability and purity were
      96% and 94%. Our results demonstrate that this advanced isolation method is
      reproducible, and can simultaneously produce high-quality primary cardiomyocytes
      and fibroblasts for the future study. 

PMID- 26300256
TI  - [Involvement of adrenomedullin in the pathogenesis of inflammatory pain and
      morphine tolerance].
AB  - The increase of pronociceptive mediators in the dorsal root ganglia (DRG) and
      spinal dorsal horn is an important mechanism in the pathogenesis of inflammatory
      pain and opioid tolerance. Adrenomedullin (AM) belongs to calcitonin gene-related
      peptide (CGRP) family and has been recently demonstrated to be a pain-related
      peptide. It has also been shown that the expression and release of AM are
      increased in the DRG and spinal dorsal horn during inflammation and repeated use
      of morphine. Intrathecal administration of the selective AM receptor antagonist
      AM22-52 abolishes inflammatory pain and morphine tolerance, suggesting that
      enhanced AM receptor signaling in the DRG and spinal dorsal horn contributes to
      the induction of inflammatory pain and morphine tolerance. The present review
      highlights the recent developments regarding the involvement of AM in these two
      disorders. The neurological mechanisms of AM's actions are also discussed. 

PMID- 26300257
TI  - [Crosstalk between Wnt5a and inflammatory signaling in inflammation].
AB  - Wnt5a belongs to the large WNT family of cysteine-rich secreted glycoproteins,
      which is involved in multiple signaling pathways that regulate a variety of
      cellular processes, including cell motility, proliferation differentiation and so
      on during development. The regulation and signaling transduction of Wnt5a have
      been reported to closely relate to inflammatory response, which indicates that
      Wnt5a plays a critical role in the occurrence and development of inflammatory
      diseases. In this review, we summarized data on Wnt5a and its signaling pathway,
      as well as their involvement in inflammatory response. Further comprehensive
      understanding of the function and relationship between Wnt5a and inflammatory
      response would help us to develop novel diagnostic and therapeutic strategies for
      prevention and treatment of inflammatory diseases. 

PMID- 26300258
TI  - Pre-organized Guide RNA in the Cas9 Complex Is Ready for the Selection of Target
      Double-Stranded DNA.
AB  - The 3 D structure of Cas9 bound with sgRNA was solved by X-ray crystal-structure
      analysis. The conformation change in SpyCas9 upon binding to sgRNA changes Cas9
      to target-DNA-recognition mode in which seed segments in sgRNA are pre-ordered in
      an A-type conformation.

PMID- 26300259
TI  - Survivors of Homicide: Mental Health Outcomes, Social Support, and Service Use
      Among a Community-Based Sample.
AB  - This study aims to explore rates of bereavement-related mental health outcomes
      and diagnostic comorbidity along with the associations between mental health
      outcomes, perceived social support, knowledge of services, and service use among
      a diverse sample of 47 survivors 2 years post loss. Findings are consistent with
      prior studies in that homicide is associated with an overlapping of significant
      symptom presentation of posttraumatic stress disorder (PTSD), major depressive
      disorder (MDD), and complicated grief (CG). Lack of grief-specific social support
      was demonstrated to be associated with PTSD and MDD but not with CG. Although a
      significant number of survivors reported poor mental health outcomes, a limited
      number were using services.

PMID- 26300260
TI  - MacroH2A1 and ATM Play Opposing Roles in Paracrine Senescence and the Senescence
      Associated Secretory Phenotype.
AB  - Oncogene-induced senescence (OIS) is a tumor-suppressive mechanism typified by
      stable proliferative arrest, a persistent DNA damage response, and the senescence
      associated secretory phenotype (SASP), which helps to maintain the senescent
      state and triggers bystander senescence in a paracrine fashion. Here, we
      demonstrate that the tumor suppressive histone variant macroH2A1 is a critical
      component of the positive feedback loop that maintains SASP gene expression and
      triggers the induction of paracrine senescence. MacroH2A1 undergoes dramatic
      genome-wide relocalization during OIS, including its removal from SASP gene
      chromatin. The removal of macroH2A1 from SASP genes results from a negative
      feedback loop activated by SASP-mediated endoplasmic reticulum (ER) stress. ER
      stress leads to increased reactive oxygen species and persistent DNA damage
      response including activation of ATM, which mediates removal macroH2A1 from SASP
      genes. Together, our findings indicate that macroH2A1 is a critical control point
      for the regulation of SASP gene expression during senescence.

PMID- 26300261
TI  - Lack of Evidence for PKM2 Protein Kinase Activity.
AB  - The role of pyruvate kinase M2 (PKM2) in cell proliferation is controversial. A
      unique function of PKM2 proposed to be important for the proliferation of some
      cancer cells involves the direct activity of this enzyme as a protein kinase;
      however, a detailed biochemical characterization of this activity is lacking.
      Using [(32)P]-phosphoenolpyruvate (PEP) we examine the direct substrates of PKM2
      using recombinant enzyme and in vitro systems where PKM2 is genetically deleted.
      Labeling of some protein species from [(32)P]-PEP can be observed; however, most
      were dependent on the presence of ADP, and none were dependent on the presence of
      PKM2. In addition, we also failed to observe PKM2-dependent transfer of phosphate
      from ATP directly to protein. These findings argue against a role for PKM2 as a
      protein kinase.

PMID- 26300262
TI  - MCM9 Is Required for Mammalian DNA Mismatch Repair.
AB  - DNA mismatch repair (MMR) is an evolutionarily conserved process that corrects
      DNA polymerase errors during replication to maintain genomic integrity. In E.
      coli, the DNA helicase UvrD is implicated in MMR, yet an analogous helicase
      activity has not been identified in eukaryotes. Here, we show that mammalian
      MCM9, a protein involved in replication and homologous recombination, forms a
      complex with MMR initiation proteins (MSH2, MSH3, MLH1, PMS1, and the clamp
      loader RFC) and is essential for MMR. Mcm9-/- cells display microsatellite
      instability and MMR deficiency. The MCM9 complex has a helicase activity that is
      required for efficient MMR since wild-type but not helicase-dead MCM9 restores
      MMR activity in Mcm9-/- cells. Moreover, MCM9 loading onto chromatin is MSH2
      dependent, and in turn MCM9 stimulates the recruitment of MLH1 to chromatin. Our
      results reveal a role for MCM9 and its helicase activity in mammalian MMR.

PMID- 26300263
TI  - Ancient Origin of cGAS-STING Reveals Mechanism of Universal 2',3' cGAMP
      Signaling.
AB  - In humans, the cGAS-STING immunity pathway signals in response to cytosolic DNA
      via 2',3' cGAMP, a cyclic dinucleotide (CDN) second messenger containing mixed 2'
      5' and 3'-5' phosphodiester bonds. Prokaryotes also produce CDNs, but these are
      exclusively 3' linked, and thus the evolutionary origins of human 2',3' cGAMP
      signaling are unknown. Here we illuminate the ancient origins of human cGAMP
      signaling by discovery of a functional cGAS-STING pathway in Nematostella
      vectensis, an anemone species >500 million years diverged from humans. Anemone
      cGAS appears to produce a 3',3' CDN that anemone STING recognizes through
      nucleobase-specific contacts not observed in human STING. Nevertheless, anemone
      STING binds mixed-linkage 2',3' cGAMP indistinguishably from human STING,
      trapping a unique structural conformation not induced by 3',3' CDNs. These
      results reveal that human mixed-linkage cGAMP achieves universal signaling by
      exploiting a deeply conserved STING conformational intermediate, providing
      critical insight for therapeutic targeting of the STING pathway. 

PMID- 26300264
TI  - Human Hsp70 Disaggregase Reverses Parkinson's-Linked alpha-Synuclein Amyloid
      Fibrils.
AB  - Intracellular amyloid fibrils linked to neurodegenerative disease typically
      accumulate in an age-related manner, suggesting inherent cellular capacity for
      counteracting amyloid formation in early life. Metazoan molecular chaperones
      assist native folding and block polymerization of amyloidogenic proteins,
      preempting amyloid fibril formation. Chaperone capacity for amyloid disassembly,
      however, is unclear. Here, we show that a specific combination of human Hsp70
      disaggregase-associated chaperone components efficiently disassembles alpha
      synuclein amyloid fibrils characteristic of Parkinson's disease in vitro.
      Specifically, the Hsc70 chaperone, the class B J-protein DNAJB1, and an Hsp110
      family nucleotide exchange factor (NEF) provide ATP-dependent activity that
      disassembles amyloids within minutes via combined fibril fragmentation and
      depolymerization. This ultimately generates non-toxic alpha-synuclein monomers.
      Concerted, rapid interaction cycles of all three chaperone components with
      fibrils generate the power stroke required for disassembly. This identifies a
      powerful human Hsp70 disaggregase activity that efficiently disassembles amyloid
      fibrils and points to crucial yet undefined biology underlying amyloid-based
      diseases.

PMID- 26300267
TI  - Hyperconjugation in diethyl ether cation versus diethyl sulfide cation.
AB  - Ionization of a molecule can greatly alter its electronic structure as well as
      its geometric structure. In this collaborative experimental and theoretical
      study, we examined variance in hyperconjugation upon ionization of diethyl ether
      (DEE) and diethyl sulfide (DES). We obtained the experimental gas phase
      vibrational spectra of DEE, DES, DEE(+), DES(+), DEE(+)-Ar, and DES(+)-Ar in the
      wavenumber region of 2500 to 3600 cm(-1). For DEE(+) and DEE(+)-Ar, we observed a
      greatly red shifted CH stretching peak at 2700 cm(-1), while the lowest CH
      stretching peaks for DEE, DES, DES(+) and DES(+)-Ar were observed around 2850 cm(
      1). For DEE(+), we calculated a drastic red shifted CH stretching peak at 2760
      cm(-1), but for DEE, DES, and DES(+) the lowest CH stretching peaks were
      calculated to be at 2860, 2945, and 2908 cm(-1), respectively. In addition, for
      DEE, the minima (maxima) geometry in the neutral state becomes a maxima (minima)
      geometry in the cationic state, while similar minima geometries are seen in
      neutral and cationic states of DES. These experimental and theoretical findings
      were rationalized through the natural bond orbital analysis by quantifying the
      hyperconjugation between the sigmaCH orbital and the ionized singly occupied p
      orbital of the oxygen (sulfur) in DEE(+) (DES(+)). This study showed how
      orientation with the ionized orbital can greatly affect the neighboring CH bond
      strength and its polarity, as well as the geometry of the system. Furthermore,
      this change in the CH bond strength between DEE(+) and DES(+) is quantified from
      the energies for intramolecular proton transfer in the two cations. 

PMID- 26300266
TI  - Protective effect of TiO2 nanowhiskers on Tetra Sulphonatophenyl Porphyrin (TSPP)
      complexes induced oxidative stress during photodynamic therapy.
AB  - BACKGROUND: Tetra Sulphonatophenyl Porphyrin (TSPP) is well known photosensitizer
      for photodynamic therapy; nevertheless, its well-known adverse effects hamper its
      potential use. Recently, nano TiO2's potential role in biomedical has been
      defined for various disease theranostics, including cancer and other infections.
      Thus, in this contribution we have explored the possibility of utilizing TiO2
      nanowhiskers as novel strategy to lower TSPP adverse effects both in vitro, and
      in vivo. METHODS: Various concentrations of TSPP, TiO2-TSPP, and TiO2 were
      injected to three different rat groups, while fourth group was kept as control.
      Toxic effects were evaluated on excretory and circulatory system by using
      histopathology, fluorescent microscopy, complete blood cells count (CBC) and
      serum enzymes. RESULTS: In complete blood cells count, all cells were
      significantly (p<0.01) affected by the various concentration and treatment
      groups. The various dose concentrations and treatment also significantly (p<0.01)
      affected the serum enzyme parameters including AST, ALT, LDH, Creatinine and BUN
      level. The low concentration of TSPP-TiO2 was found to be the safest, on the
      bases of serum enzyme parameters, CBC, histopathology, and fluorescent
      microscopic analysis. The MTT assay was used to evaluate in vitro cytotoxicity,
      and the results demonstrated maximum viability in illuminated TSPP-TiO2
      nanowhiskers group when compared with TSPP treated group. CONCLUSIONS: It was
      evident that increase in concentration of TSPP increased the toxic effects;
      however, the TiO2 nanowhiskers combination with TSPP decreased these adverse
      effects. Moreover, TSPP (0.1 mM) combined with TiO2 nanowhiskers (0.6 mM) was
      safer than TSPP (0.1 mM) alone.

PMID- 26300265
TI  - Global Promoter Targeting of a Conserved Lysine Deacetylase for Transcriptional
      Shutoff during Quiescence Entry.
AB  - Quiescence is a conserved cell-cycle state characterized by cell-cycle arrest,
      increased stress resistance, enhanced longevity, and decreased transcriptional,
      translational, and metabolic output. Although quiescence plays essential roles in
      cell survival and normal differentiation, the molecular mechanisms leading to
      this state are not well understood. Here, we determined changes in the
      transcriptome and chromatin structure of S. cerevisiae upon quiescence entry. Our
      analyses revealed transcriptional shutoff that is far more robust than previously
      believed and an unprecedented global chromatin transition, which are tightly
      correlated. These changes require Rpd3 lysine deacetylase targeting to at least
      half of gene promoters via quiescence-specific transcription factors including
      Xbp1 and Stb3. Deletion of RPD3 prevents cells from establishing transcriptional
      quiescence, leading to defects in quiescence entry and shortening of
      chronological lifespan. Our results define a molecular mechanism for global
      reprogramming of transcriptome and chromatin structure for quiescence driven by a
      highly conserved chromatin regulator.

PMID- 26300268
TI  - Clinical implications and outcome prediction in chronic hemodialysis patients
      with lower serum potassium*uric acid product.
AB  - BACKGROUND: The aims of this study were to evaluate correlations between serum
      potassium (S[K]) and uric acid (S[UA]) in hemodialysis patients and to determine
      whether lower levels of both S[K] and S[UA] were associated with poor long-term
      prognoses in these patients. METHODS: A cohort of 424 maintenance hemodialysis
      patients (58+/-13 years of age; 47% male; 39% with diabetes) from a single center
      were divided into tertiles based on the product of S[K]*S[UA] (K*UA): Group 1:
      low K*UA: n=141; Group 2: median K*UA: n=141; and Group 3: high K*UA: n=142. The
      longest observation period was 60 months. RESULTS: S[K] showed a positive linear
      correlation with S[UA] (r=0.33; p<0.001). In multivariate logistic regression
      analysis, Group 1 was characterized by hypoalbuminemia (odds ratio [OR]=0.20, 95%
      confidence interval (CI)=0.11-0.35) and lower levels of normalized protein
      catabolism [nPCR] (OR=0.10, 95%CI=0.05-0.22) and phosphate levels (OR=0.41,
      95%CI=0.33-0.51). In contrast, Group 3 was associated with higher nPCR (OR=6.07,
      95%CI=2.93-12.50) and albumin levels (OR=2.12, 95% CI=2.12-7.00). Compared to the
      reference (Group 1), the hazard ratio (HR) for long-term mortality was
      significantly lower in Groups 2 (HR=0.65, 95%CI=0.43-0.99) and 3 (HR=0.56,
      95%CI=0.36-0.89). In multivariate Cox proportional analysis, the risk of
      mortality decreased by 2% (HR=0.98; 95%CI=0.96-0.99) per 1 unit increase in K*UA
      product. CONCLUSION: Hemodialysis patients with lower S[K] and [UA] levels were
      characterized by hypoalbuminemia and lower nPCR, and they were associated with a
      long-term mortality risk.

PMID- 26300269
TI  - Cost-effectiveness analysis of preoperative treatment of acromegaly with
      somatostatin analogue on surgical outcome.
AB  - CONTEXT: There is no uniform standard of care for acromegaly. Due to the high
      costs involved, steps must be taken to ensure the cost-effective delivery of
      treatment. OBJECTIVE: Taking the results of an earlier meta-analysis as a
      starting point, this study aims to determine whether treatment with long-acting
      somatostatin analogue (SSA) prior to surgery improves the cost-effectiveness of
      the treatment of acromegaly. METHODS: The results are presented as an Incremental
      Cost Effectiveness Ratio (ICER) immediately after surgery, for the following year
      and over the next four decades. The cure rates percentage (95% CI) for the three
      randomized prospective controlled trials were 44.4% (34.2-54.7) and 18.2% (10.1
      26.3) for preoperative treated and untreated patients respectively. The cost of
      pharmacological treatments was based on the number of units prescribed, dose and
      length of treatment. RESULTS: The mean (95% CI) ICER immediately after surgery
      was ?17,548 (12,007-33,250). In terms of the postoperative SSA treatment, the
      ICER changes from positive to negative before two years after surgery. One decade
      after surgery the ICER per patient/year was ?-9973 (-18,798; -6752) for
      postoperative SSA treatment and ?-31,733 (-59,812; -21,483) in the case of
      postoperative pegvisomant treatment. CONCLUSIONS: In centres without optimal
      surgical results, preoperative treatment of GH-secreting pituitary macroadenomas
      with SSA not only shows a significant improvement in the surgical results, but is
      also highly cost-effective, with an ICER per patient/year one decade after
      surgery, of between ?-9973 (-18,798; -6752) and ?-31,733 (-59,812; -21,483) for
      SSA and pegvisomant respectively.

PMID- 26300270
TI  - Trajectory and Predictors of Depression and Anxiety Disorders in Mothers With the
      FMR1 Premutation.
AB  - BACKGROUND: Although the FMR1 premutation is associated with elevated prevalence
      of psychiatric disorders, the longitudinal course of symptoms has not been
      established. The present study followed a sample of women with the FMR1
      premutation to characterize the incidence, stability, and predictors of mood and
      anxiety disorders across a 3-year period. METHODS: Participants included 83 women
      with the FMR1 premutation (mean age = 38.35) who completed the Structured
      Clinical Interview for DSM-IV Axis I Disorders at two time points, 3 years apart.
      Additional information was obtained regarding demographic, child, and biomedical
      (e.g., medication, menopause, CGG repeats) factors. RESULTS: We found increased
      prevalence of major depressive disorder (MDD) and anxiety disorders over time,
      with adverse outcomes predicted by complex interactions among biological,
      behavioral, and environmental risk factors. Lifetime MDD increased from 46% to
      54% and lifetime anxiety disorders increased from 28% to 35%. Midrange CGG
      repeats, elevated child problem behaviors, and divorced marital status conveyed
      elevated risk for psychiatric diagnoses. Primary ovarian insufficiency was highly
      prevalent (41%) but did not account for elevated rates of psychiatric diagnoses.
      Medication use was highly reported (41%), particularly in women with MDD or
      anxiety, with selective serotonin reuptake inhibitors reported as the most
      commonly used medication across diagnostic groups. CONCLUSIONS: The elevated
      prevalence of depression and anxiety in women with the FMR1 premutation is a
      clear and pressing concern given the frequent occurrence of the FMR1 premutation
      in the general community and the adverse outcomes-at both individual and systems
      levels-associated with psychiatric disorders in this population.

PMID- 26300271
TI  - Expanding the Reach of Biological Psychiatry with Biological Psychiatry:
      Cognitive Neuroscience and Neuroimaging.

PMID- 26300273
TI  - Oxytocin and Memory of Emotional Stimuli: Some Dance to Remember, Some Dance to
      Forget.
AB  - An ever-growing body of evidence suggests that the hypothalamic neuropeptide
      oxytocin plays a central role in the regulation of mammalian social behavior and
      relationships. Yet, mammalian social interactions are extremely complex,
      involving both approach and avoidance behaviors toward specific individuals.
      While in the past oxytocin was conceived merely as a prosocial molecule that
      nonselectively facilitated affiliative emotions and behavior, it is now
      recognized that oxytocin plays a role in a wide range of social relationships,
      some of which involve negative emotions such as fear, aggression, and envy and
      lead to avoidance behavior. However, the way by which a single molecule such as
      oxytocin contributes to contrasting emotions and opposite behaviors is yet to be
      discovered. Here, we discuss the role of oxytocin in the modulation of emotional
      memories in rodents, focusing on two paradigms: social recognition and fear
      conditioning, representing approach and avoidance behaviors, respectively. We
      review recent pioneering studies that address the complex effects of oxytocin in
      a mechanistic approach, using genetic animal models and brain region-specific
      manipulations of oxytocin activity. These studies suggest that the multiple roles
      of oxytocin in social and fear behavior are due to its local effects in various
      brain areas, most notably distinct regions of the amygdala. Finally, we propose a
      model explaining some of the contradictory effects of oxytocin as products of the
      balance between two networks in the amygdala that are controlled by the medial
      prefrontal cortex. 

PMID- 26300274
TI  - A novel cytologic sampling technique to diagnose subclinical endometritis and
      comparison of staining methods for endometrial cytology samples in dairy cows.
AB  - The present article describes a study of the diagnosis of subclinical
      endometritis in dairy cows having two principal aims: first, to validate a novel
      technique for taking endometrial cytology samples to diagnose subclinical
      endometritis in dairy cows. Second, to compare the percentage of
      polymorphonuclear cells (PMNs) in cytology samples stained with Diff-Quik versus
      a specific staining method for PMNs, naphthol-AS-D-chloroacetate-esterase (CIAE).
      In the first experiment, Holstein-Friesian cows (n = 204) were used to take two
      cytology samples at the same time using the conventional cytobrush (CB) and the
      new cytotape (CT). Both devices were assembled within the same catheter allowing
      sampling at the same time, and approximately at the same location. Cytotape
      consisted of a 1.5-cm piece of paper tape rolled on the top of an insemination
      catheter covered with a double guard sheet. Parameters used to evaluate both
      methods were: PMNs percentage, total cellularity, quality of the smears, and red
      blood cell contamination. The concordance correlation coefficient analysis was
      used to assess agreement between continuous and Pearson chi-square tests for
      categorical variables. Agreement between the percentage of PMNs in both methods
      was good rho = 0.84 (0.79, 0.87) with a minor standard error of 2%. Both methods
      yielded similar total cellularity (P = 0.62). Cytotape yielded better quality
      smears with more intact cells (P < 0.01) while samples that were taken by CB were
      more likely to be bloody (P < 0.01). Hence, CT and CB methods yielded smears with
      a similar PMNs percentage and a total number of cells, but CT provided smears
      with higher quality and significantly less blood contamination. For the second
      experiment, 114 duplicate cytology slides were stained using both Diff-Quik and
      CIAE. Agreement between PMNs percentage in both staining techniques was good rhoc
      = 0.84 (0.78, 0.89) with a standard error of only 2%. Hence, Diff-Quik was
      confirmed as an easy, fast, and high-quality staining technique, which can be
      routinely used to stain endometrial cytology samples satisfactorily. 

PMID- 26300272
TI  - Diffusion Tensor Imaging Provides Evidence of Possible Axonal Overconnectivity in
      Frontal Lobes in Autism Spectrum Disorder Toddlers.
AB  - BACKGROUND: Theories of brain abnormality in autism spectrum disorder (ASD) have
      focused on underconnectivity as an explanation for social, language, and
      behavioral deficits but are based mainly on studies of older autistic children
      and adults. METHODS: In 94 ASD and typical toddlers ages 1 to 4 years, we
      examined the microstructure (indexed by fractional anisotropy) and volume of axon
      pathways using in vivo diffusion tensor imaging of fronto-frontal, fronto
      temporal, fronto-striatal, and fronto-amygdala axon pathways, as well as
      posterior contrast tracts. Differences between ASD and typical toddlers in the
      nature of the relationship of age to these measures were tested. RESULTS: Frontal
      tracts in ASD toddlers displayed abnormal age-related changes with greater
      fractional anisotropy and volume than normal at younger ages but an overall
      slower than typical apparent rate of continued development across the span of
      years. Posterior cortical contrast tracts had few significant abnormalities.
      CONCLUSIONS: Frontal fiber tracts displayed deviant early development and age
      related changes that could underlie impaired brain functioning and impact social
      and communication behaviors in ASD.

PMID- 26300275
TI  - Risk factors associated with uterine fluid after breeding caused by Streptococcus
      zooepidemicus.
AB  - Infectious endometritis is a major cause of infertility in the mare and inflicts
      major losses on the equine breeding industry. The ability of the mare to
      eliminate uterine infections has been studied intensively for decades; however,
      despite identification of several factors contributing to the multifactorial
      pathogenesis and improved treatment, infectious endometritis remains a
      significant problem in a subpopulation of broodmares. Streptococcus equi subsp.
      zooepidemicus (S. zooepidemicus) is one of the most commonly isolated pathogens
      from the uterus of mares, suffering from infectious endometritis. Its ability to
      cause chronic latent infection by residing deep within the endometrial tissue has
      previously been described. The aim of the present study was to correlate
      different mare risk factors to infectious endometritis and pregnancy rates in
      broodmares and to investigate whether clonal or genetically distinct S.
      zooepidemicus strains isolated from mares with endometritis were associated with
      mare risk factors and the outcome of insemination. Mares (N = 152) were examined
      after natural cover, and 20% (31 mares) had intrauterine fluid (IUF)
      accumulation. Fifty-five percent (16 of 29) of the mares with IUF had infectious
      endometritis, and S. zooepidemicus was isolated in 81% (13 of 16) of these mares.
      Significantly more resting mares had IUF compared with foaling mares, and the
      foaling mares had the highest prevalence of positive bacterial growth from the
      uterine swab. The per-cycle pregnancy rate for the study was 63%. Pregnancy rate
      was significantly negatively affected by increased age (>12 years) and increased
      parity (>4), and the lowest pregnancy rate was observed in resting mares compared
      with foaling, barren, and maiden mares. Up to four S. zooepidemicus isolates were
      selected from each mare with growth of S. zooepidemicus from the uterine swab
      sample and further characterized by pulsed-field gel electrophoresis. In total,
      S. zooepidemicus isolates from 18 mares were analyzed with pulsed-field gel
      electrophoresis. In 13 mares, the isolates selected from each mare showed a high
      genetic relatedness within each individual mare, whereas two genetically distinct
      strains were isolated in five mares. A clonal S. zooepidemicus infection was
      associated with increased age, high parity, and poor vulvar conformation. Mares
      with clonal infection had a low pregnancy rate (38%) compared with mares with two
      strains isolated (80%). In conclusion, the results indicate that clonal S.
      zooepidemicus endometritis is associated with increased age, parity, and poor
      vulvar conformation in the broodmare. 

PMID- 26300276
TI  - Hair care practices and structural evaluation of scalp and hair shaft parameters
      in African American and Caucasian women.
AB  - How African American hair fragility relates to hair care practices and biologic
      differences between races is not well understood. To assess the differences
      between perceptions of hair health, hair care practices, and several biologic
      hair parameters between Caucasian and African American women. A questionnaire on
      perceptions of hair health and hair care practices was administered. Biological
      and structural parameters of hair shaft and scalp, including growth, density,
      diameter, cycle, breakage, and scalp blood flow were also assessed in this case
      control study. Significant differences between the Caucasian and African American
      women were observed in the questionnaire and biologic study data. Regarding self
      reported perceptions of hair health, there were differences in the following:
      hair shaft type (P < 0.001), hair breakage (P = 0.040), and desire to change hair
      (P = 0.001). Regarding self-reported hair care practices, there were differences
      in the following: location of haircutting (P = 0.002) and washing (P = 0.010),
      washing frequency (P < 0.001), chemical relaxer use (P < 0.001), hooded hair
      dryer use (P < 0.001), and hair shaft conditioner use (P = 0.005). The two groups
      had similar practices in regard to the use of hair color, frequency of hair color
      use, chemical curling agents, and handheld blow dryer use. Regarding biological
      and structural parameters, there were differences in the following: hair growth
      rate (P < 0.001), density (P = 0.0016), diameter (P = 0.01), number of broken
      hairs (P < 0.001), and blood flow (P = 0.03). There was no significant difference
      in hair cycle parameters.The differences in hair care practices and hair fiber
      morphology among African American women may contribute to clinically observed
      variation in hair fragility and growth. 

PMID- 26300277
TI  - Dinuclear copper(I) complexes with N-heterocyclic thione and selone ligands:
      synthesis, characterization, and electrochemical studies.
AB  - The synthesis, characterization, and structures of a series of homoleptic and
      heteroleptic copper(I) complexes supported by N-heterocyclic chalcogenone ligands
      is reported herein. The quasi-reversible Cu(II/I) reduction potentials of these
      copper complexes with monodentate (dmit or dmise) and/or bidentate (Bmm(Me),
      Bsem(Me), Bme(Me), Bsee(Me)) chalcogenone ligands are highly dependent upon the
      nature and number of the donor groups and can be tuned over a 470 mV range (-369
      to 102 mV). Copper-selone complexes have more negative Cu(II/I) reduction
      potentials relative to their thione analogs by an average of 137 mV, and
      increasing the number of methylene units linking the heterocyclic rings in the
      bidentate ligands results in more negative reduction potentials for their copper
      complexes. This ability to tune the copper reduction potentials over a wide range
      has potential applications in synthetic and industrial catalysis as well as the
      understanding of important biological processes such as electron transfer in blue
      copper proteins and respiration.

PMID- 26300279
TI  - Cell-free DNA testing: how to choose which laboratory to use?

PMID- 26300278
TI  - Systemic Administration of siRNA via cRGD-containing Peptide.
AB  - Although small interfering RNAs (siRNAs) have been demonstrated to specifically
      silence their target genes in disease models and clinical trials, in vivo siRNA
      delivery is still the technical bottleneck that limits their use in therapeutic
      applications. In this study, a bifunctional peptide named RGD10-10R was designed
      and tested for its ability to deliver siRNA in vitro and in vivo. Because of
      their electrostatic interactions with polyarginine (10R), negatively charged
      siRNAs were readily complexed with RGD10-10R peptides, forming spherical RGD10
      10R/siRNA nanoparticles. In addition to enhancing their serum stability by
      preventing RNase from attacking siRNA through steric hindrance, peptide binding
      facilitated siRNA transfection into MDA-MB-231 cells, as demonstrated by FACS and
      confocal microscopy assays and by the repressed expression of target genes. When
      RGD10 peptide, a receptor competitor of RGD10-10R, was added to the transfection
      system, the cellular internalization of RGD10-10R/siRNA was significantly
      compromised, suggesting a mechanism of ligand/receptor interaction. Tissue
      distribution assays indicated that the peptide/siRNA complex preferentially
      accumulated in the liver and in several exocrine/endocrine glands. Furthermore,
      tumor-targeted delivery of siRNA was also demonstrated by in vivo imaging and
      cryosection assays. In summary, RGD10-10R might constitute a novel siRNA delivery
      tool that could potentially be applied in tumor treatment. 

PMID- 26300280
TI  - Impact of adult growth hormone deficiency on metabolic profile and cardiovascular
      risk [Review].
AB  - Adult growth hormone deficiency (GHD) is a well defined clinical condition, which
      is characterized by abnormal body composition, impaired physical activity and
      decreased quality of life. In addition, in recent years, growing interest has
      been shown towards cardiovascular risks in adult patients affected by GHD. In
      this regard, GHD is widely known to be associated with increased mortality,
      likely due to the increase of risk factors, such as central obesity, impaired
      lipid and glucose profiles and other less-known risk factors, such as
      inflammatory cytokines, endothelial dysfunction and oxidative stress. However,
      very few papers have recently discussed this topic. In this review, the aim is to
      clarify this issue by discussing evidence regarding the effects of adult GHD on
      metabolic and cardiovascular profiles. 

PMID- 26300281
TI  - Ceftaroline in vitro activity against methicillin-resistant Staphylococcus aureus
      and coagulase-negative Staphylococci: a short report from Italy.

PMID- 26300282
TI  - Metaphyseal Engaging Short and Ultra-Short Anatomic Cementless Stems in Young and
      Active Patients.
AB  - We report 400 patients (mean age, 53 years) who received a short stem (17.8 years
      of follow-up) and 201 patients (mean age 53 years) who received an ultra-short
      stem (12.3 years of follow-up). At the final follow-up, the mean Harris hip
      score, WOMAC score and the mean UCLA activity scores were not different between
      two groups. No patient had thigh pain in either group. Two hips (0.3%) in the
      short stem group were revised because of early postoperative infection and one
      hip (0.2%) in the ultra-short stem group was revised for fracture of the proximal
      femur. Metaphyseal engaging short and ultra-short anatomic cementless stem
      without diaphyseal fixation provided long-term durable fixation in young and
      active patients.

PMID- 26300283
TI  - Ascorbic acid provides protection for human chondrocytes against oxidative
      stress.
AB  - Oxidative stress is considered to be an important cause of dysfunction in
      chondrocytes and articular cartilage degradation, which leads to the pathogenesis
      of osteoarthritis (OA) and cartilage aging. The present study aimed to assess the
      effects of the widely applied antioxidant, ascorbic acid (AA), on human
      chondrocytes against hydrogen peroxide (H2O2) in vitro. Using annexin V
      fluorescein isothiocyanate, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium
      bromide and senescence-associated beta-galactosidase assays, the present study
      identified that AA reduced apoptosis, reduced the loss of viability and markedly
      decreased H2O2-mediated senescence in cells treated with H2O2. Furthermore, AA
      not only stimulated the expression levels of collagens and proteoglycans, but
      also inhibited the differentiation of chondrocytes under conditions of oxidative
      stress. In addition, reverse transcription-quantitative polymerase chain reaction
      and western blotting demonstrated that AA decreased the activity of nrf2, NF
      kappaB, AP1 and matrix metalloproteinase-3, which is stimulated by H2O2. In
      conclusion, AA efficiently protected human chondrocytes against damage induced by
      H2O2 by regulating multiple regulatory pathways.

PMID- 26300285
TI  - The use of digit ratios and dextrality to detect atypical neurodevelopment in
      schizotypy.

PMID- 26300284
TI  - Aggression in Malaysian schizophrenia patients: Its clinical determinants and
      association with COMT Val158Met genotypes.

PMID- 26300286
TI  - Hydrogen bonds in Zif268 proteins - a theoretical perspective.
AB  - The aim of the work was to elucidate the presence of different hydrogen bond (H
      bond) in five Zif268 proteins (1A1F, 1A1G, 1A1H, 1A1I and 1A1K). For this
      purpose, we have performed the QM/MM and molecular dynamics (MD) studies, the
      results of which reveal that H-bonds depend on the amino acid sequence and
      orientation of the H-bond donor atoms. Further, high specificity of Arg and Asn
      is observed for guanine and adenine, respectively. Furthermore, both conventional
      and non-conventional hydrogen bond also exists in the proteins, among them N-H?O
      H-bonds are the strongest. Besides, the non-conventional bonds play a role in the
      protein folding and DNA stacking. From the QSAR properties, amino acids such as
      asparagine and aspartic acids are the major reactive sites in the Zif268 protein.
      The electron affinities of Zif268 proteins are high, so the charge transfer
      occurs from the DNA to the protein molecules. NBO analysis indicates the majority
      of charge transfer occurs from DNA to the corresponding anti-bonding orbital of
      the peptides. Root mean square deviation and Rg (radius of gyration) show that
      1A1F is more compact and in native state during MD simulation. The minimum Rg
      leads to the large number of hydrogen bonds formation in 1A1F. Higher solvent
      accessible surface area in 1A1I indicates that the cavity inside the protein is
      large. 

PMID- 26300287
TI  - Green approaches to late-stage fluorination: radiosyntheses of (18)F-labelled
      radiopharmaceuticals in ethanol and water.
AB  - Green strategies for late-stage fluorination with (18)F, in which ethanol and
      water are the only solvents used throughout the entire radiolabeling process
      (azeotropic drying, nucleophilic fluorination, purification and formulation),
      have been developed and applied to the radiosyntheses of a range of
      radiopharmaceuticals commonly employed in clinical PET imaging. 

PMID- 26300288
TI  - A high-efficiency gamma-MnO2-like catalyst in toluene combustion.
AB  - A novel gamma-MnO2 catalyst obtained by selective removal and other traditional
      MnO2 catalysts (alpha-, beta-, delta-MnO2) were studied for their catalytic
      performance in toluene combustion. The new gamma-MnO2 catalyst showed the best
      catalytic activity owing to its three-dimensional macroporous and mesoporous
      morphology and the gamma-MnO2-like structure. 

PMID- 26300289
TI  - The interleukin-1beta-511 T>C (rs16944) gene polymorphism is associated with risk
      of developing silent myocardial ischemia in diabetic patients.
AB  - Silent myocardial ischemia (SMI) is a multifactorial and polygenic disorder that
      results from an excessive inflammatory response. Considering the prominent role
      of IL-1beta, IL-1F10 and IL-1RN as regulators of the inflammatory process and
      vascular physiology, the aim of the present study was to analyze whether IL
      1beta, IL-1F10 and IL-1RN single nucleotide polymorphisms (SNPs) are associated
      with SMI. One polymorphism was associated with risk of SMI. Under co-dominant,
      recessive and additive models, the IL-1beta-511 T>C polymorphism was associated
      with increased risk of SMI when compared to healthy controls (OR=4.68, 95%CI=2.21
      9.92, pCCo-dom=0.0048; OR=3.97, 95%CI=1.97-7.99, pCRec=0.0024; OR=2.02,
      95%CI=1.41-2.90, pCAdd=0.0024, respectively). All models were adjusted for
      gender, age and smoking. Linkage disequilibrium analysis showed four haplotypes
      (CTCC, CCTC, CCCT and CTCC) with increased frequency in SMI patients when
      compared to healthy controls (OR=2.53, 95%CI=1.47-4.36, pC=0.0009, OR=2.34,
      95%CI=1.15-4.74, pC=0.02, OR=2.44, 95%CI=1.14-5.18, pC=0.02, OR=5.11, 95%CI=1.37
      19.05, pC=0.01, respectively). In summary, our data suggest that the IL-1beta-511
      T>C polymorphism plays an important role in the development of SMI in diabetic
      patients. In addition, in our study was possible to distinguish one protective
      and four risk haplotypes for development of SMI. 

PMID- 26300290
TI  - More Than a Feeling: Public Expectations About Emotional Responses to Criminal
      Victimization.
AB  - Crime victims' emotional display in legal settings has been found to influence
      credibility judgments. The specific nature of public expectations about crime
      victims' emotional responses have, however, not been adequately investigated. In
      an experimental vignette study, respondents in a community sample (N = 404)
      estimated the likelihood that female and male victims would experience 7 distinct
      emotions in response to 5 types of crimes. Across all crime types, female victims
      were expected to experience significantly more situation-focused (anxiety, fear)
      and inward-focused (guilt, shame, sadness) emotions, and significantly less other
      focused emotions (hatred, anger) than male victims. This calls for an increased
      focus on distinct emotions in future research on victim's emotions. Implications
      for victims in legal and social settings are discussed. 

PMID- 26300291
TI  - New primers for detecting and quantifying denitrifying anaerobic methane
      oxidation archaea in different ecological niches.
AB  - The significance of ANME-2d in methane sink in the environment has been
      overlooked, and there was no any study evaluating the distribution of ANME-2d in
      the environment. New primers were thus needed to be designed for following
      research. In this paper, a pair of primers (DP397F and DP569R) was designed to
      quantify ANME-2d. The specificity and amplification efficiency of this primer
      pair were acceptable. PCR amplification of another pair of primers (DP142F and
      DP779R) generated a single, bright targeted band from the enrichment sample, but
      yielded faint, multiple bands from the environmental samples. Nested PCR was
      conducted using the primers DP142F/DP779R in the first round and DP142F/DP569R in
      the second round, which generated a bright targeted band. Further phylogenetic
      analysis showed that these targeted bands were ANME-2d-related sequences. Real
      time PCR showed that the copies of the 16s ribosomal RNA gene of ANME-2d in these
      samples ranged from 3.72 * 10(4) to 2.30 * 10(5) copies MUg(-1) DNA, indicating
      that the percentage of ANME-2d was greatest in a polluted river sample and least
      in a rice paddy sample. These results demonstrate that the newly developed real
      time PCR primers could sufficiently quantify ANME-2d and that nested PCR with an
      appropriate combination of the new primers could successfully detect ANME-2d in
      environmental samples; the latter finding suggests that ANME-2d may spread in
      environments.

PMID- 26300292
TI  - Advances in microbial biosynthesis of metal nanoparticles.
AB  - Metal nanoparticles are garnering considerable attention owing to their high
      potential for use in various applications in the material, electronics, and
      energy industries. Recent research efforts have focused on the biosynthesis of
      metal nanomaterials using microorganisms rather than traditional chemical
      synthesis methods. Microorganisms have evolved to possess molecular machineries
      for detoxifying heavy metals, mainly by employing metal-binding proteins and
      peptides. Biosynthesis of diverse metal nanoparticles has recently been
      demonstrated using such heavy metal detoxification systems in microorganisms,
      which provides several advantages over the traditional chemical synthesis
      methods. First, metal nanoparticles can be synthesized at mild temperatures, such
      as at room temperature, with less energy input. Second, no toxic chemicals or
      reagents are needed, and thus the process is environmentally friendly. Third,
      diverse metal nanoparticles, including those that have never been chemically
      synthesized, can be biosynthesized. Here, we review the strategies for the
      biosynthesis of metal nanoparticles using microorganisms, and provide future
      prospects. 

PMID- 26300293
TI  - Re-cultivation of Neochloris oleoabundans in exhausted autotrophic and
      mixotrophic media: the potential role of polyamines and free fatty acids.
AB  - Neochloris oleoabundans (Chlorophyta) is widely considered one of the most
      promising microalgae for biotechnological applications. However, the large-scale
      production of microalgae requires large amounts of water. In this perspective,
      the possibility of using exhausted growth media for the re-cultivation of N.
      oleoabundans was investigated in order to simultaneously make the cultivation
      more economically feasible and environmentally sustainable. Experiments were
      performed by testing the following media: autotrophic exhausted medium (E+) and
      mixotrophic exhausted medium after cultivation with glucose (EG+) of N.
      oleoabundans cells grown in a 20-L photobioreactor (PBR). Both exhausted media
      were replenished with the same amounts of nitrate and phosphate as the control
      brackish medium (C). Growth kinetics, nitrate and phosphate consumption,
      photosynthetic pigments content, photosynthetic efficiency, cell morphology, and
      lipid production were evaluated. Moreover, the free fatty acid (FFA) composition
      of exhausted media and the polyamine (PA) concentrations of both algae and media
      were analyzed in order to test if some molecules, released into the medium, could
      influence algal growth and metabolism. Results showed that N. oleoabundans can
      efficiently grow in both exhausted media, if appropriately replenished with the
      main nutrients (E+ and EG+), especially in E+ and to the same extent as in C
      medium. Growth promotion of N. oleoabundans was attributed to PAs and alteration
      of the photosynthetic apparatus to FFAs. Taken together, results show that
      recycling growth medium is a suitable solution to obtain good N. oleoabundans
      biomass concentrations, while providing a more sustainable ecological impact on
      water resources. 

PMID- 26300294
TI  - Development of the dichlorvos-ammonia (DV-AM) method for the visual detection of
      aflatoxigenic fungi.
AB  - Aflatoxins (AFs) are carcinogenic and toxic secondary metabolites produced mainly
      by Aspergillus flavus and Aspergillus parasiticus. To monitor and regulate the AF
      contamination of crops, a sensitive and precise detection method for these
      toxigenic fungi in environments is necessary. We herein developed a novel visual
      detection method, the dichlorvos-ammonia (DV-AM) method, for identifying AF
      producing fungi using DV and AM vapor on agar culture plates, in which DV
      inhibits the esterase in AF biosynthesis, causing the accumulation of
      anthraquinone precursors (versiconal hemiacetal acetate and versiconol acetate)
      of AFs in mycelia on the agar plate, followed by a change in the color of the
      colonies from light yellow to brilliant purple-red by the AM vapor treatment. We
      also investigated the appropriate culture conditions to increase the color
      intensity. It should be noted that other species producing the same precursors of
      AFs such as Aspergillus nidulans and Aspergillus versicolor could be
      discriminated from the Aspergillus section Flavi based on the differences of
      their phenotypes. The DV-AM method was also useful for the isolation of
      nonaflatoxigenic fungi showing no color change, for screening microorganisms that
      inhibit the AF production by fungi, and for the characterization of the fungi
      infecting corn kernels. Thus, the DV-AM method can provide a highly sensitive and
      visible indicator for the detection of aflatoxigenic fungi. 

PMID- 26300295
TI  - Serological and coprological analyses for the diagnosis of Fasciola gigantica
      infections in bovine hosts from Sargodha, Pakistan.
AB  - A serological and coprological survey of fasciolosis was conducted in bovine
      hosts from the Sargodha district, Pakistan using excretory-secretory (ES)
      antigens of Fasciola gigantica from cattle and buffaloes. Livers, faecal and
      blood samples of 146 cattle and 184 buffaloes were collected from slaughterhouses
      and examined for the presence of any Fasciola in bile ducts and ova in faeces.
      Serum was separated. ES antigens were prepared by incubating adult Fasciola in
      phosphate-buffered saline for 6-8 h and then filtering using a 0.22-MUm syringe
      filter. Checkerboard titration was performed and optimum concentrations of
      antigen and serum were determined. Sero-prevalence was found to be 50.00 and
      38.35% in buffalo and cattle, respectively. Using liver examination as the gold
      standard, enzyme-linked immunosorbent assay (ELISA) sensitivity was found to be
      100% in both buffalo and cattle as compared with that of coprological examination
      in buffalo (61.79%) and cattle (54.54%). This indigenous ELISA was also highly
      specific, with values of 96.84 and 98.90% in buffalo and cattle, respectively.
      Positive predictive values were calculated as 96.74 and 98.21% in buffalo and
      cattle, respectively, while negative predictive values were 100%. For the
      validation of indigenous ELISA in field surveys, faecal and blood samples were
      collected from six sub-districts (tehsils) in the district of Sargodha. Sera were
      screened for the presence of anti-fasciola antibodies using both the indigenous
      and commercial ELISA kits. While both kits were equally sensitive, the indigenous
      ELISA was found to be more specific. The highest prevalence of fasciolosis was
      found in December, as ascertained using both serological and coprological
      examination. Significant differences were found in prevalences of fasciolosis in
      different sub-districts and age groups, together with feeding and watering
      systems. 

PMID- 26300296
TI  - Christensen vs Biomet Microfixation alloplastic TMJ implant: Are there
      improvements? A numerical study.
AB  - The objective of this study was to compare the load transfer mechanism and
      behavior of two total temporomandibular joint (TMJ) prostheses: Biomet and
      Christensen TMJ models were simulated. Computed tomography (CT) images from a
      specific patient were used to generate two models for use in simulation of
      implantation for the total temporomandibular prostheses. Three finite element
      models were created in all. One considered the intact temporomandibular joint and
      two received a temporomandibular implant. In the simulation we considered the
      five most important muscles acting on the mandible and incisor teeth support. The
      Christensen model reduced strain in the opposite condyle by around 50% while
      increasing strain in the implanted condyle. The changes in the posterior side of
      the implanted condyle present an increase of five times the minimum principal
      strain, suggesting some bone fatigue. With the Biomet implant, the reduction in
      strain in the implanted condyle on the posterior side was around 100%, suggesting
      the possibility of some bone loss proximally near the resection plane. Based on
      our results, we conclude that in both models the implants influence the behavior
      of the mandible by improving the symmetry of the mandible and strain
      distribution. The Biomet implant modifies the behavior of the mandible slightly
      and presents some improvements over the Christensen TMJ model in strain
      distribution and tensions in the opposite intact disc similar to the non
      implanted situation. 

PMID- 26300298
TI  - Laparoscopic upper-pole heminephrectomy for duplicated renal collecting system
      with superselective artery clamping using virtual partial nephrectomy analysis of
      Synapse Vincent: A case report.
AB  - A 22-year-old woman was diagnosed with a duplicated renal collecting system with
      hydronephrosis and parenchymal loss in the upper pole of the left kidney. She
      underwent laparoscopic left upper-pole nephrectomy. Although a complex hilar
      vascular anatomy was identified during the operation, preoperative three
      dimensional computed tomographic reconstruction using a three-dimensional image
      analysis device (Synapse Vincent; Fuji Medical Systems, Tokyo, Japan) greatly
      helped to accurately identify the anatomical renal hilum. For further detail,
      virtual partial nephrectomy analysis using a Voronoi decomposition was used to
      visualize the area supplied by a selected arterial branch including the atrophic
      cleavage line. We controlled the bleeding with selective clamping and safely
      carried out upper-pole heminephrectomy according to the preoperative plan. 

PMID- 26300299
TI  - Case of alopecia universalis accompanied by minimal change nephrotic syndrome.

PMID- 26300297
TI  - Understanding HIV-infected patients' experiences with PEPFAR-associated
      transitions at a Centre of Excellence in KwaZulu Natal, South Africa: a
      qualitative study.
AB  - South Africa was the largest recipient of funding from the President's Emergency
      Plan for AIDS Relief (PEPFAR) for antiretroviral therapy (ART) programs from 2004
      to 2012. Funding decreases have led to transfers from hospital and non
      governmental organization-based care to government-funded, community-based
      clinics. We conducted semi-structured interviews with 36 participants to assess
      patient experiences related to transfer of care from a PEPFAR-funded, hospital
      based clinic in Durban to either primary care clinics or hospital-based clinics.
      Participant narratives revealed the importance of connectedness between patients
      and the PEPFAR-funded clinic program staff, who were described as respectful and
      conscientious. Participants reported that transfer clinics were largely focused
      on dispensing medication and on throughput, rather than holistic care. Although
      participants appreciated the free treatment at transfer sites, they expressed
      frustration with long waiting times and low perceived quality of patient-provider
      communication, and felt that they were treated disrespectfully. These factors
      eroded confidence in the quality of the care. The transfer was described by
      participants as hurried with an apparent lack of preparation at transfer clinics
      for new patient influx. Formal (e.g., counseling) and informal (e.g., family)
      social supports, both within and beyond the PEPFAR-funded clinic, provided a
      buffer to challenges faced during and after the transition in care. These data
      support the importance of social support, adequate preparation for transfer, and
      improving the quality of care in receiving clinics, in order to optimize
      retention in care and long-term adherence to treatment. 

PMID- 26300301
TI  - Predictors of binge drinking in elderly Americans.
AB  - BACKGROUND: The increasing trend in elderly binge drinking in the U.S. is cause
      for alarm. We sought to describe the predictors of binge drinking in elderly men
      and women and evaluate the relationship between binge drinking and mental health
      disorders in this population. METHODS: The 2008 Centers for Disease Control's
      Behavioral Risk Factor Surveillance Survey was utilized to identify a cohort of
      4,815 individuals in the U.S. of age 65 or older. The primary outcome of interest
      was self-reported binge drinking, defined as an affirmative response to the
      question: "How many times in the past 30 days have you had more than five drinks
      (in men) or more than four drinks (in women) on an occasion?" RESULTS: Among
      4,815 elderly participants studied, a total of 466 (9.7%) participants reported
      binge drinking over the past 30 days while 4,349 (90.3%) participants reported no
      binge drinking. Binge drinking was not associated with anxiety or depressive
      disorders in the overall population, however, elderly women reporting binge
      drinking had higher rates of depressive disorders. In multivariate analysis,
      independent predictors of binge drinking in elderly participants included younger
      age, male gender, smoking, absence of college education, lower annual income, and
      absence of coronary artery disease. Predictors of binge drinking differed in
      elderly men and women. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Younger age, male
      gender, smoking, lack of college education, lower annual income, and absence of
      coronary artery disease are independently associated with higher rates of binge
      drinking among elderly Americans. Elderly men and women had disparate predictors
      of binge drinking. This study provides valuable information to be applied to the
      substance abuse screening process in elderly men and women.

PMID- 26300300
TI  - Social interaction reward decreases p38 activation in the nucleus accumbens shell
      of rats.
AB  - We have previously shown that animals acquired robust conditioned place
      preference (CPP) to either social interaction alone or cocaine alone. Recently it
      has been reported that drugs of abuse abnormally activated p38, a member of
      mitogen-activated protein kinase family, in the nucleus accumbens. In this study,
      we aimed to investigate the expression of the activated form of p38 (pp38) in the
      nucleus accumbens shell and core of rats expressing either cocaine CPP or social
      interaction CPP 1 h, 2 h and 24 h after the CPP test. We hypothesized that
      cocaine CPP will increase pp38 in the nucleus accumbens shell/core as compared to
      social interaction CPP. Surprisingly, we found that 24 h after social interaction
      CPP, pp38 neuronal levels were decreased in the nucleus accumbens shell to the
      level of naive rats. Control saline rats that received saline in both
      compartments of the CPP apparatus and cocaine CPP rats showed similar enhanced
      p38 activation as compared to naive and social interaction CPP rats. We also
      found that the percentage of neurons expressing dopaminergic receptor D2R and
      pp38 was also decreased in the shell of the nucleus accumbens of social
      interaction CPP rats as compared to controls. Given the emerging role of p38 in
      stress/anxiety behaviors, these results suggest that (1) social interaction
      reward has anti-stress effects; (2) cocaine conditioning per se does not affect
      p38 activation and that (3) marginal stress is sufficient to induce p38
      activation in the shell of the nucleus accumbens. 

PMID- 26300303
TI  - Fabrication of Microfluidic Valves Using a Hydrogel Molding Method.
AB  - In this paper, a method for fabricating a microfluidic valve made of
      polydimethylsiloxane (PDMS) using a rapid prototyping method for microchannels
      through hydrogel cast molding is discussed. Currently, the valves in
      microchannels play an important role in various microfluidic devices. The
      technology to prototype microfluidic valves rapidly is actively being developed.
      For the rapid prototyping of PDMS microchannels, a method that uses a hydrogel as
      the casting mold has been recently developed. This technique can be used to
      prepare a three-dimensional structure through simple and uncomplicated methods.
      In this study, we were able to fabricate microfluidic valves easily using this
      rapid prototyping method that utilizes hydrogel cast molding. In addition, we
      confirmed that the valve displacement could be predicted within a range of
      constant pressures. Moreover, because microfluidic valves fabricated using this
      method can be directly observed from a cross-sectional direction, we anticipate
      that this technology will significantly contribute to clarifying fluid behavior
      and other phenomena in microchannels and microfluidic valves with complex
      structures. 

PMID- 26300302
TI  - Human Erythroid 5-Aminolevulinate Synthase Mutations Associated with X-Linked
      Protoporphyria Disrupt the Conformational Equilibrium and Enhance Product
      Release.
AB  - Regulation of 5-aminolevulinate synthase (ALAS) is at the origin of balanced heme
      production in mammals. Mutations in the C-terminal region of human erythroid
      specific ALAS (hALAS2) are associated with X-linked protoporphyria (XLPP), a
      disease characterized by extreme photosensitivity, with elevated blood
      concentrations of free protoporphyrin IX and zinc protoporphyrin. To investigate
      the molecular basis for this disease, recombinant hALAS2 and variants of the
      enzyme harboring the gain-of-function XLPP mutations were constructed, purified,
      and analyzed kinetically, spectroscopically, and thermodynamically. Enhanced
      activities of the XLPP variants resulted from increases in the rate at which the
      product 5-aminolevulinate (ALA) was released from the enzyme. Circular dichroism
      spectroscopy revealed that the XLPP mutations altered the microenvironment of the
      pyridoxal 5'-phosphate cofactor, which underwent further and specific alterations
      upon succinyl-CoA binding. Transient kinetic analyses of the variant-catalyzed
      reactions and protein fluorescence quenching upon binding of ALA to the XLPP
      variants demonstrated that the protein conformational transition step associated
      with product release was predominantly affected. Of relevance is the fact that
      XLPP could also be modeled in cell culture. We propose that (1) the XLPP
      mutations destabilize the succinyl-CoA-induced hALAS2 closed conformation and
      thus accelerate ALA release, (2) the extended C-terminus of wild-type mammalian
      ALAS2 provides a regulatory role that allows for allosteric modulation of
      activity, thereby controlling the rate of erythroid heme biosynthesis, and (3)
      this control is disrupted in XLPP, resulting in porphyrin accumulation. 

PMID- 26300304
TI  - In vivo immunotoxicity of perfluorooctane sulfonate in BALB/c mice:
      Identification of T-cell receptor and calcium-mediated signaling pathway
      disruption through gene expression profiling of the spleen.
AB  - Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant that is used
      worldwide and is continuously being detected in biota and the environment, thus
      presenting potential threats to the ecosystem and human health. Although PFOS is
      highly immunotoxic, its underlying molecular mechanisms remain largely unknown.
      The present study examined PFOS-induced immunotoxicity in the mouse spleen and
      explored its underlying mechanisms by gene expression profiling. Oral exposure of
      male BALB/c mice for three weeks followed by one-week recovery showed that a 10
      mg/kg/day PFOS exposure damaged the splenic architecture, inhibited T-cell
      proliferation in response to mitogen, and increased the percentages of T helper
      (CD3(+)CD4(+)) and cytotoxic T (CD3(+)CD8(+)) cells, despite the decrease in the
      absolute number of these cells. A delayed type of PFOS immunotoxicity was
      observed, which mainly occurred during the recovery period. Global gene
      expression profiling of mouse spleens and QRT-PCR analyses suggest that PFOS
      inhibited the expression of genes involved in cell cycle regulation and NRF2
      mediated oxidative stress response, and upregulated those in TCR signaling,
      calcium signaling, and p38/MAPK signaling pathways. Western blot analysis
      confirmed that the expressions of CAMK4, THEMIS, and CD3G, which were involved in
      the upregulated pathways, were induced upon PFOS exposure. Acute PFOS exposure
      modulated calcium homoeostasis in splenocytes. These results indicate that PFOS
      exposure can activate TCR signaling and calcium ion influx, which provides a clue
      for the potential mechanism of PFOS immunotoxicity. The altered signaling
      pathways by PFOS treatment as revealed in the present study might facilitate in
      better understanding PFOS immunotoxicity and explain the association between
      immune disease and PFOS exposure. 

PMID- 26300305
TI  - PRED treatment mediated stable and efficient water oxidation performance of the
      Fe2O3 nano-coral structure.
AB  - Herein, we demonstrate that an electrochemical surface treatment of Fe foil with
      simple pulse reverse electrodeposition (PRED) prior to thermal oxidation can
      substantially enhance the photoelectrochemical (PEC) stability and water
      splitting performance of Fe2O3/Fe photoanodes. Comprehensive structural (XRD,
      FESEM, and HRTEM), compositional (XPS depth profiling), and electrochemical (EIS
      and Mott-Schottky) analyses were performed to understand the effect of PRED
      treatment on the PEC performance of fabricated photoanodes. It is revealed that
      air-exposed Fe foil is prone to formation of a loosely bound surface oxide layer
      that, upon annealing at 800  degrees C, results in an unstable Fe2O3 nano-flake
      (2-3 MUm long) morphology. In contrast, when such Fe foil is pre-treated with
      PRED to etch the loosely bound oxide layer, adherent inverse-opal-like nano-coral
      structures (60-100 nm thin) are formed. In addition to stability improvement,
      PRED-treatment also assists in exposing the photocatalytically active high index
      [104] facet sites of hematite. Thin hematite nano-coral structures with high
      index [104] facet sites significantly improved the separation of photo-generated
      charge carriers and oxygen evolution kinetics, resulting in performance
      enhancement with excellent photocurrent stability for extended duration in a 1 M
      NaOH solution under one sun illumination. The net photocurrent density for nano
      coral morphology was 0.813 mA cm(-2) at 1.23 V vs. RHE, which is the highest
      reported value for pristine hematite photoanodes fabricated from Fe foil. 

PMID- 26300306
TI  - Apparent ileal digestibility of nutrients and amino acids in soybean meal, fish
      meal, spray-dried plasma protein and fermented soybean meal to weaned pigs.
AB  - This study sought to determine whether fermentation could increase apparent ileal
      digestibility (AID) of dry matter (DM), nitrogen (N), energy (E) and amino acids
      (AA) in fermented soybean meal (FSBM) greater than that of soybean meal (SBM) in
      weaned pigs. Four weaned pigs (10.00 +/- 0.30 kg) were surgically equipped with T
      cannulas and randomly followed a 4 * 4 Latin square design of treatments (SBM,
      FSBM, fish meal and spray-dried plasma protein). Overall, the fermentation
      process was able to reduce the amount of anti-nutritional factors (ANF),
      including trypsin inhibitors, raffinose and stachyose, in the FSBM diet, which
      were significantly reduced by 39.4, 92.2, and 92.9%, respectively, as compared to
      the SBM diet. As a consequence of ANF reduction in FSBM, the AID of DM, N and E
      as well as AA was significantly greater with FSBM than SBM. Taken all together,
      the fermentation process improved the nutritional quality of SBM, due to ANF
      reduction, leading to improvement of digestibility of AA. As such, FSBM can be
      potentially used as a specialized feed ingredient, especially for young animal
      diets in an attempt to reduce diet costs. 

PMID- 26300308
TI  - Pituitary abnormalities in patients with Fanconi anaemia.

PMID- 26300307
TI  - A chameleon-inspired stretchable electronic skin with interactive colour changing
      controlled by tactile sensing.
AB  - Some animals, such as the chameleon and cephalopod, have the remarkable
      capability to change their skin colour. This unique characteristic has long
      inspired scientists to develop materials and devices to mimic such a function.
      However, it requires the complex integration of stretchability, colour-changing
      and tactile sensing. Here we show an all-solution processed chameleon-inspired
      stretchable electronic skin (e-skin), in which the e-skin colour can easily be
      controlled through varying the applied pressure along with the applied pressure
      duration. As such, the e-skin's colour change can also be in turn utilized to
      distinguish the pressure applied. The integration of the stretchable, highly
      tunable resistive pressure sensor and the fully stretchable organic
      electrochromic device enables the demonstration of a stretchable
      electrochromically active e-skin with tactile-sensing control. This system will
      have wide range applications such as interactive wearable devices, artificial
      prosthetics and smart robots. 

PMID- 26300309
TI  - An uncommon cause of distributive shock: Lessons from two consecutive cases of
      idiopathic systemic capillary leak syndrome (Clarkson's disease).

PMID- 26300310
TI  - Epidural analgesia in ICU: Useful and effective probably, safe maybe.

PMID- 26300311
TI  - The survey of anaesthesia in France describes the challenges for the future.

PMID- 26300312
TI  - Microwave frequency electromagnetic fields (EMFs) produce widespread
      neuropsychiatric effects including depression.
AB  - Non-thermal microwave/lower frequency electromagnetic fields (EMFs) act via
      voltage-gated calcium channel (VGCC) activation. Calcium channel blockers block
      EMF effects and several types of additional evidence confirm this mechanism. Low
      intensity microwave EMFs have been proposed to produce neuropsychiatric effects,
      sometimes called microwave syndrome, and the focus of this review is whether
      these are indeed well documented and consistent with the known mechanism(s) of
      action of such EMFs. VGCCs occur in very high densities throughout the nervous
      system and have near universal roles in release of neurotransmitters and
      neuroendocrine hormones. Soviet and Western literature shows that much of the
      impact of non-thermal microwave exposures in experimental animals occurs in the
      brain and peripheral nervous system, such that nervous system histology and
      function show diverse and substantial changes. These may be generated through
      roles of VGCC activation, producing excessive neurotransmitter/neuroendocrine
      release as well as oxidative/nitrosative stress and other responses. Excessive
      VGCC activity has been shown from genetic polymorphism studies to have roles in
      producing neuropsychiatric changes in humans. Two U.S. government reports from
      the 1970s to 1980s provide evidence for many neuropsychiatric effects of non
      thermal microwave EMFs, based on occupational exposure studies. 18 more recent
      epidemiological studies, provide substantial evidence that microwave EMFs from
      cell/mobile phone base stations, excessive cell/mobile phone usage and from
      wireless smart meters can each produce similar patterns of neuropsychiatric
      effects, with several of these studies showing clear dose-response relationships.
      Lesser evidence from 6 additional studies suggests that short wave, radio
      station, occupational and digital TV antenna exposures may produce similar
      neuropsychiatric effects. Among the more commonly reported changes are sleep
      disturbance/insomnia, headache, depression/depressive symptoms,
      fatigue/tiredness, dysesthesia, concentration/attention dysfunction, memory
      changes, dizziness, irritability, loss of appetite/body weight,
      restlessness/anxiety, nausea, skin burning/tingling/dermographism and EEG
      changes. In summary, then, the mechanism of action of microwave EMFs, the role of
      the VGCCs in the brain, the impact of non-thermal EMFs on the brain, extensive
      epidemiological studies performed over the past 50 years, and five criteria
      testing for causality, all collectively show that various non-thermal microwave
      EMF exposures produce diverse neuropsychiatric effects.

PMID- 26300313
TI  - Functional expression of a putative geraniol 8-hydroxylase by reconstitution of
      bacterially expressed plant CYP76F45 and NADPH-cytochrome P450 reductase CPR I
      from Croton stellatopilosus Ohba.
AB  - While attempting to isolate the enzyme geranylgeraniol 18-hydroxylase, which is
      involved in plaunotol biosynthesis in Croton stellatopilosus (Cs), the cDNAs for
      a cytochrome P450 monooxygenase(designated as CYP76F45) and an NADPH-cytochrome
      P450 reductase (designated as CPR I based on its classification) were isolated
      from the leaf. The CYP76F45 and CsCPR I genes have open reading frames (ORFs)
      encoding 507- and 711-amino acid proteins with predicted relative molecular
      weights of 56.7 and 79.0 kDa,respectively. Amino acid sequence comparison showed
      that both CYP76F45 (63-73%) and CsCPR I (79-83%) share relatively high sequence
      identities with homologous proteins in other plant species.Phylogenetic tree
      analysis confirmed that CYP76F45 belongs to the CYP76 family and that CsCPR I
      belongs to Class I of dicotyledonous CPRs, with both being closely related to
      Ricinus communis genes. Functional characterization of both enzymes, each
      expressed separately in Escherichia coli as recombinant proteins,showed that only
      simultaneous incubation of the membrane bound proteins with the substrate
      geraniol (GOH) and the coenzyme NADPH could form 8-hydroxygeraniol. The enzyme
      mixture could also utilize acyclic sesquiterpene farnesol (FOH) with a comparable
      substrate preference ratio (GOH:FOH) of 54:46. The levelsof the CYP76F45 and
      CsCPR I transcripts in the shoots, leaves and twigs of C. stellatopilosus were
      correlated with the levels of a major monoterpenoid indole alkaloid, identified
      tentatively as 19-Evallesamine,that accumulated in these plant parts. These
      results suggested that CYP76F45 and CPR I function as the enzyme geraniol-8
      hydroxylase (G8H), which is likely to be involved in the biosynthesis of the
      indole alkaloid in C. stellatopilosus [corrected].

PMID- 26300314
TI  - Contributions of long-term tillage systems on crop production and soil properties
      in the semi-arid Loess Plateau of China.
AB  - BACKGROUND: This study determined the long-term effect of tillage systems on soil
      properties and crop yields in a semi-arid environment. Field pea (Pisum sativum
      L.) and spring wheat (Triticum aestivum L.) were alternately grown in six tillage
      systems at Dingxi (35 degrees  28' N, 104 degrees  44' E), north-west China
      starting in 2001. RESULTS: After the first 6 years of experiments, conventional
      tillage with stubble incorporating (TS) and no-till with stubble cover (NTS)
      increased soil organic matter by 9.9% and 13.0%, respectively, compared to the
      conventional tillage with stubble removed (T); both TS and NTS also increased
      soil microbial counts, available K and P, and total N. No-till with stubble
      removed (NT), NTS and NTP (no-till with plastic mulching) had 20.7%, 62.6% and
      43.7% greater alkaline phosphatase activity compared to the T treatment. Soil
      catalase, urease and invertase activities were all greater in the no-till
      treatments than in the T treatment. Averaged across 6 years, both wheat and pea
      achieved highest grain yields under NTS treatment. CONCLUSION: No-till with
      stubble retention is the most promising system for improving soil physical,
      biological and chemical properties, and increasing crop yields, and thus, this
      system can be adopted in areas with conditions similar to the semi-arid north
      west China. (c) 2015 Society of Chemical Industry.

PMID- 26300315
TI  - DAL-1/4.1B contributes to epithelial-mesenchymal transition via regulation of
      transforming growth factor-beta in lung cancer cell lines.
AB  - The present study aimed to investigate the effects of the tumor suppressor gene
      differentially expressed in adenocarcinoma of the lung 1 (DAL-1)/4.1B on early
      stage adenocarcinoma of the lung. The role of DAL-1/4.1B in the epithelial
      mesenchymal transition (EMT), which is implicated in cancer metastasis, was
      examined using DAL-1 knockdown and overexpression, followed by polymerase chain
      reaction and western blot analysis of EMT markers, as well as cell counting and
      cell migration/invasion assays. The results showed that DAL-1/4.1B has a role in
      transforming growth factor (TGF)-beta-induced EMT in non-small cell lung cancer
      cells. Silencing of DAL-1/4.1B with inhibitory RNAs altered the expression of
      numerous EMT markers, including E-cadherin and beta-catenin, whereas
      overexpression of DAL-1/4.1B had the opposite effect. In addition, DAL-1/4.1B
      expression was induced following TGF-beta treatment at the protein and mRNA
      level. DAL-1/4.1B deficiency impaired TGF-beta-induced EMT and increased cell
      migration and invasion. These results suggested that DAL-1/4.1B contributed to
      the EMT and may be important for tumor metastasis in lung cancer. Together with
      the results of a previous study by our group, the present study suggested that
      DAL-1/4.1B acts as a tumor suppressor in the early transformation process in lung
      cancer, while in later stages, it functions as an oncogene affecting the
      biological features of human lung carcinoma cells. The results of the present
      study provided evidence for the feasibility of utilizing DAL-1/4.1B as a target
      for lung cancer gene therapy.

PMID- 26300316
TI  - Characterization of antibody V segment diversity in the Tasmanian devil
      (Sarcophilus harrisii).
AB  - The Tasmanian devil (Sarcophilus harrisii) immune system has recently been under
      scrutiny because of the emergence of a contagious cancer, which has decimated
      devil numbers. Here we provide a comprehensive description of the Tasmanian devil
      immunoglobulin variable regions. We show that heavy chain variable (VH) and light
      chain variable (VL) repertoires are similar to those described in other marsupial
      taxa: VL diversity is high, but VH diversity is restricted and belongs only to
      clan III. As in other mammals, one VH and one Vlambda germline family and
      multiple incomplete Vkappa germline sequences were identified in the genome. High
      Vkappa variation was observed in transcripts and we predict that it may have
      arisen by gene conversion and/or somatic mutations, as it does not appear to have
      originated from germline variation. Phylogenetic analyses revealed that devil VL
      gene segments are highly complex and ancient, with some lineages predating the
      separation of marsupials and eutherians. These results indicate that although the
      evolutionary history of immune genes lead to the expansions and contractions of
      immune gene families between different mammalian lineages, some of the ancestral
      immune gene variants are still maintained in extant species. A high degree of
      similarity was found between devil and other marsupial VH segments, demonstrating
      that they originated from a common clade of closely related sequences. The VL
      families had a higher variation than VH both between and within species. We
      suggest that, similar to other studied marsupial species, the complex VL segment
      repertoire compensates for the limited VH diversity in Tasmanian devils. 

PMID- 26300317
TI  - Immune responses of pigs immunized with a recombinant porcine reproductive and
      respiratory syndrome virus expressing porcine GM-CSF.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) has spread worldwide,
      causing huge economic losses to the swine industry. The current PRRSV vaccines
      have failed to provide broad protection against various strains. Granulocyte
      macrophage colony-stimulating factor (GM-CSF), an efficacious adjuvant, has been
      shown to enhance the immunogenicity of various vaccines. The purpose of this
      study was to construct a recombinant live attenuated PRRSV that expresses porcine
      GM-CSF (pGM-CSF) and evaluate the immune responses of pigs immunized with the
      recombinant virus. The results showed that the recombinant PRRSV was successfully
      rescued and had similar growth properties to parental virus grown in Marc-145
      cells. The recombinant virus was stable for 10 passages in cell culture. Pigs
      intramuscularly immunized with the recombinant virus produced a similar humoral
      response to that elicited using parental virus. With regard to cell-mediated
      immunity assessed in peripheral blood, the recombinant virus induced higher
      proportion of CD4(+)CD8(+) double-positive T cells (DPT), higher IFN-gamma level
      at 0 and 7 days post-challenge (DPC), and lower viremia at 21 DPC than pigs
      immunized with parental virus. These results indicate that recombinant PRRSV
      expressing pGM-CSF can induce a significant higher cellular immune response and
      reduce the persistent infection compared pigs vaccinated with the parental virus.
      This is first report of evaluation of immune response in pigs elicited by a
      recombinant live attenuated PRRSV expressing porcine GM-CSF. It may represent a
      novel strategy for future development of genetic engineered vaccines against
      PRRSV infection. 

PMID- 26300318
TI  - Nonalcoholic fatty liver disease: Roles of the gut and the liver and metabolic
      modulation by some dietary factors and especially long-chain n-3 PUFA.
AB  - Nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis
      (NASH), is the leading cause of chronic liver disease in Western countries. NASH
      increases the risk for fibrosis, cirrhosis, and hepatocellular carcinoma. The
      mechanisms underlying the steatosis to NASH transition remain incompletely
      understood despite recent progress in cellular and molecular aspects. Our primary
      aim is to analyze recent advances in understanding deviations in hepatic fat
      metabolism and the implication of gut physiology and microbiota in this
      transition. Our second aim is to gather experimental and clinical data on the
      capability of long-chain n-3 PUFA (LC n-3 PUFA), including docosahexaenoic (DHA)
      and eicosapentaenoic (EPA) acids to prevent or alleviate NAFLD. Our main
      conclusions are: (i) increasing data support a pivotal role for the gut toward
      NASH development; (ii) LC n-3 PUFA have often proven preventive or therapeutic
      effect toward NASH development in rodent models. In patients with NASH they
      appear to have no therapeutic effects, but they could have preventive effects,
      which require to define better the specific roles, modes of action, and doses of
      DHA and EPA. 

PMID- 26300319
TI  - Genome analysis and polar tube firing dynamics of mosquito-infecting
      microsporidia.
AB  - Microsporidia are highly divergent fungi that are obligate intracellular
      pathogens of a wide range of host organisms. Here we review recent findings from
      the genome sequences of mosquito-infecting microsporidian species Edhazardia
      aedis and Vavraia culicis, which show large differences in genome size, although
      similar numbers of predicted genes. We also show a video of E. aedis polar tube
      firing, which is the dramatic mechanism used by microsporidia to deliver the germ
      cell (sporoplasm) into the host cell to initiate intracellular infection. 

PMID- 26300320
TI  - Multiple functions of neuronal plasma membrane neurotransmitter transporters.
AB  - Removal from receptors of neurotransmitters just released into synapses is one of
      the major steps in neurotransmission. Transporters situated on the plasma
      membrane of nerve endings and glial cells perform the process of neurotransmitter
      (re)uptake. Because the density of transporters in the membranes can fluctuate,
      transporters can determine the transmitter concentrations at receptors, thus
      modulating indirectly the excitability of neighboring neurons. Evidence is
      accumulating that neurotransmitter transporters can exhibit multiple functions.
      Being bidirectional, neurotransmitter transporters can mediate transmitter
      release by working in reverse, most often under pathological conditions that
      cause ionic gradient dysregulations. Some transporters reverse to release
      transmitters, like dopamine or serotonin, when activated by 'indirectly acting'
      substrates, like the amphetamines. Some transporters exhibit as one major
      function the ability to capture transmitters into nerve terminals that perform
      insufficient synthesis. Transporter activation can generate conductances that
      regulate directly neuronal excitability. Synaptic and non-synaptic transporters
      play different roles. Cytosolic Na(+) elevations accompanying transport can
      interact with plasmalemmal or/and mitochondrial Na(+)/Ca(2+) exchangers thus
      generating calcium signals. Finally, neurotransmitter transporters can behave as
      receptors mediating releasing stimuli able to cause transmitter efflux through
      multiple mechanisms. Neurotransmitter transporters are therefore likely to play
      hitherto unknown roles in multiple therapeutic treatments. 

PMID- 26300321
TI  - Determination of roxithromycin from human plasma samples based on magnetic
      surface molecularly imprinted polymers followed by liquid chromatography-tandem
      mass spectromer.
AB  - In this paper, a simple and reproducible method for the determination of
      roxithromycin in human plasma samples is proposed. The surface magnetic
      molecularly imprinted polymers (MMIPs) were utilized as sorbent. Roxithromycin
      was used as imprinted compound. The experimental results showed that the MMIPs
      had high affinity and selectivity toward roxithromycin. The extraction process
      was carried out in a single step by mixing the extraction solvent, MMIPs and
      human plasma samples by vortex. When the extraction process was completed, the
      MMIPs adsorbed the analyte were separated from the sample matrix by an external
      magnet due to the magnetism. The analyte eluted from the MMIPs was analysed by
      liquid chromatography-tandem mass spectrometry. Some main factors affecting the
      extraction of roxithromycin such as the amount of MMIPs, extraction solvent,
      extraction time, washing and elution conditions were optimized in this study. The
      calibration curve obtained by analyzing matrix-matched standards showed excellent
      linear relationship (r(2)=0.9997) in the concentration range of 10-1000ngmL(-1).
      The limit of detection and quantification obtained were 3.8 and 9.8ngmL(-1),
      respectively. The relative standard deviations of intra- and inter-day obtained
      were in the range of 3.9 %-5.5 % and 2.9 %-4.6 % with the recoveries ranging from
      86.5 % to 91.5 %. 

PMID- 26300322
TI  - Theoretical study on the dehydrogenation reaction of dihydrogen bonded phenol
      borane-trimethylamine in the excited state.
AB  - Time dependent density functional theory (TDDFT) and transition state theory
      (TST) have been performed to study the dehydrogenation process of dihydrogen
      bonded phenol-borane-trimethylamine (phenol-BTMA) in the excited state. The
      potential curve of phenol-BTMA in the ground state confirms that the
      dehydrogenation process does not occur in the ground state. The analysis of the
      geometric structure and infrared spectra demonstrate that the dihydrogen bond O
      H...H1-B of phenol-BTMA is considerably strengthened with the cleavage of O-H
      when excited to the first excited state. Based on the geometric structure in the
      first excited state, a transition state is found with the only imaginary
      frequency pointing to the formation of the hydrogen molecule. This finding
      implies the occurrence of the dehydrogenation process of phenol-BTMA in the
      excited state. The dehydrogenation reaction is fully completed in the reaction
      product and the new formed hydrogen molecule moves away from the plane of the
      benzene ring. This work provides a theoretical model for the dehydrogenation
      process of phenol-BTMA in the excited state.

PMID- 26300323
TI  - Clinical response in Mexican patients with irritable bowel syndrome treated with
      a low diet low in fermentable carbohydrates (FODMAP).
AB  - BACKGROUND: The low FODMAP diet eliminates carbohydrates and fermentable alcohols
      because they are not absorbed by the intestine, but are fermented by the
      microbiota, causing bloating and flatulence. AIMS: To evaluate the clinical
      response to the low FODMAP diet in patients with the different clinical subtypes
      of irritable bowel syndrome (IBS). MATERIALS AND METHODS: Patients attended to at
      the Gastroenterology Department in 2014 that were diagnosed with IBS based on the
      Rome III criteria were included in the study. They were managed with a low FODMAP
      diet for 21 days and their response to the symptoms of abdominal pain, bloating,
      flatulence, and stool form pre and post-diet were evaluated through the visual
      analogue scale, Bristol scale, and patient overall satisfaction. The results were
      analyzed by means, 95% CI, and the Student's t test. RESULTS: Of the 31 patients
      included in the study, 87% were women and the mean age was 46.48 years.
      Distribution was: IBS-C 64.5%, IBS-D 22.6%, and IBS-M 12.9%. The score for pain
      was 6.0 (95% CI 5.04-6.96) and the post-diet score was 2.77 (95% CI 1.60-3.95)
      (P<.001). The score for bloating was 7.10 (95% CI 6.13-8.06) and the post-diet
      score was 4.19 (95% CI 2.95-5.44) (P<.001). The score for flatulence was 5.94
      (95% CI 4.79-7.08) and the post-diet score was 3.06 (IC95% 1.99-4.14) (P<.001).
      The pre-diet Bristol Scale result was 3.68 (95% CI 3.14-4.22) and the post-diet
      result was 4.10 (95% CI 3.66-4.54) (P=.1). The satisfaction percentage was 70.9%.
      CONCLUSIONS: In this first study on a Mexican population with IBS, there was
      significant improvement of the main symptoms, including pain, bloating, and
      flatulence after treatment with a low FODMAP diet.

PMID- 26300324
TI  - [Low concordance between primary care and hospital clinical information].
AB  - OBJECTIVES: To measure the diagnostic agreement between Primary Care (PC) and
      hospital information systems, in order to assess the usefulness of health care
      records for research purposes. SETTING: Cross-sectional retrospective study
      integrating PC and hospital diagnostic information for the Aragon population
      admitted to hospital in 2010. PARTICIPANTS: 75.176 patients were analysed.
      INTERVENTIONS: Similarities, differences and the kappa index were calculated for
      each of the diagnoses recorded in both information systems. MAIN MEASUREMENTS:
      The studied diseases included COPD, diabetes, hypertension, cerebrovascular
      disease, ischaemic heart disease, asthma, epilepsy, and heart failure. RESULTS:
      Diagnostic concordance was higher in men and between 45 and 64 years. Diabetes
      was the condition showing the highest concordance (kappa index: 0.75), while
      asthma had the lowest values (kappa index: 0.34). CONCLUSIONS: The low
      concordance between the diagnostic information recorded in PC and in the hospital
      setting calls for urgent measures to ensure that healthcare professionals have a
      comprehensive picture of patient's health problems.

PMID- 26300326
TI  - Elastic Anisotropy of Trabecular Bone in the Elderly Human Vertebra.
AB  - Knowledge of the nature of the elastic symmetry of trabecular bone is fundamental
      to the study of bone adaptation and failure. Previous studies have classified
      human vertebral trabecular bone as orthotropic or transversely isotropic but have
      typically obtained samples from only selected regions of the centrum. In this
      study, the elastic symmetry of human vertebral trabecular bone was characterized
      using microfinite element (MUFE) analyses performed on 1019 cubic regions of side
      length equal to 5 mm, obtained via thorough sampling of the centrums of 18 human
      L1 vertebrae (age = 81.17 +/- 7.7 yr; eight males and ten females). An
      optimization procedure was used to find the closest orthotropic representation of
      the resulting stiffness tensor for each cube. The orthotropic elastic constants
      and orientation of the principal elastic axes were then recorded for each cube
      and were compared to the constants predicted from Cowin's fabric-based
      constitutive model (Cowin, 1985, "The Relationship Between the Elasticity Tensor
      and the Fabric Tensor," Mech. Mater., 4(2), pp. 137-147.) and the orientation of
      the principal axes of the fabric tensor, respectively. Deviations from orthotropy
      were quantified by the "orthotropic error" (van Rietbergen et al., 1996, "Direct
      Mechanics Assessment of Elastic Symmetries and Properties of Trabecular Bone
      Architecture," J. Biomech., 29(12), pp. 1653-1657), and deviations from
      transverse isotropy were determined by statistical comparison of the secondary
      and tertiary elastic moduli. The orthotropic error was greater than 50% for
      nearly half of the cubes, and the secondary and tertiary moduli differed from one
      another (p < 0.0001). Both the orthotropic error and the difference between
      secondary and tertiary moduli decreased with increasing bone volume fraction
      (BV/TV; p <= 0.007). Considering only the cubes with an orthotropic error less
      than 50%, only moderate correlations were observed between the fabric-based and
      the MUFE-computed elastic moduli (R2 >= 0.337; p < 0.0001). These results
      indicate that when using a criterion of 5 mm for a representative volume element
      (RVE), transverse isotropy or orthotropy cannot be assumed for elderly human
      vertebral trabecular bone. Particularly at low values of BV/TV, this criterion
      does not ensure applicability of theories of continuous media. In light of the
      very sparse and inhomogeneous microstructure found in the specimens analyzed in
      this study, further work is needed to establish guidelines for selecting a RVE
      within the aged vertebral centrum. 

PMID- 26300325
TI  - Intensity-modulated radiation therapy versus three-dimensional conformal
      radiation therapy with concurrent nedaplatin-based chemotherapy after radical
      hysterectomy for uterine cervical cancer: comparison of outcomes, complications,
      and dose-volume histogram parameters.
AB  - BACKGROUND: The purpose of this study is to report our clinical outcomes using
      intensity-modulated radiation therapy (IMRT) for adjuvant treatment of cervical
      cancer, compared with three-dimensional conformal radiation therapy (3DCRT), in
      terms of tumor control, complications and dose-volume histogram (DVH) parameters.
      METHODS: Between March 2008 and February 2014, 62 patients were treated with
      concurrent nedaplatin-based chemotherapy and whole-pelvic external beam radiation
      therapy (RT). Of these patients, 32 (52%) received 3DCRT and 30 (48%) received
      IMRT. RESULTS: The median follow-up periods were 40 months (range 2-74 months).
      The 3-year overall survival rate (OS), locoregional control rate (LRC) and
      progression-free survival rate (PFS) were 92, 95 and 92% in the IMRT group, and
      85, 82 and 70% in the 3DCRT group, respectively. A comparison of OS, LRC and PFS
      showed no significant differences between IMRT and 3DCRT. The 3-year cumulative
      incidences of grade 2 or higher chronic gastrointestinal (GI) complications were
      significantly lower with IMRT compared to 3DCRT (3% vs. 45%, p < .02) and in
      patients with V40 of the small bowel loops of <=340 mL compared to those with
      >340 mL (3% vs. 45%, p < .001). Patients treated with IMRT had a higher incidence
      of grade 3 acute hematologic complications (p < .05). V40 and V45 of the small
      bowel loops or bowel bag were predictive for development of both acute and
      chronic GI complications. CONCLUSIONS: Our results suggest that IMRT for adjuvant
      treatment of cervical cancer is useful for decreasing GI complications without
      worsening outcomes.

PMID- 26300327
TI  - Radiation induced liver disease: A clinical update.
AB  - Radiation-induced liver disease (RILD) or radiation hepatitis is a sub-acute form
      of liver injury due to radiation. It is one of the most dreaded complications of
      radiation which prevents radiation dose escalation and re-irradiation for
      hepatobiliary or upper gastrointestinal malignancies. This complication should be
      kept in mind whenever a patient is planned for irradiation of these malignancies.
      Although, incidence of RILD is decreasing due to better knowledge of liver
      tolerance, improved investigation modalities and modern radiation delivery
      techniques, treatment options are still limited. In this review article, we have
      focussed on patho-physiology, risk factors, prevention and management of RILD. 

PMID- 26300328
TI  - Experimental Signature of Microheterogeneity in Ionic Liquid-H2 O Systems and
      Their Perturbation by Adding Li(+) Salts: A Pulsed Gradient Spin-Echo NMR
      Approach.
AB  - Distinct microheterogeneity has been observed in the [OMIM]Br-H2 O system, which
      is interestingly perturbed by the addition of Li(+) salts, indicating unusual
      diffusivity of [OMIM]Br and H2 O molecules. However, the diffusional dynamics of
      water clusters show contrasting salting behavior at higher concentrations of
      Li(+) salts, following the classical salting phenomenon in lower amounts. In
      contrast, the existing microheterogeneity in the [BMIM]Br-H2 O system is weak
      enough to show any perturbation caused by the Li(+) salts on the NMR time scale. 

PMID- 26300329
TI  - Long-term effects of cognitive therapy on biological rhythms and depressive
      symptoms: A randomized clinical trial.
AB  - OBJECTIVE: To evaluate the effect of cognitive therapy on biological rhythm and
      depressive and anxious symptoms in a twelve-month follow-up period. In addition,
      correlations between the reduction of depression and anxiety symptoms and the
      regulation of biological rhythm were observed. METHODS: This was a randomized
      clinical trial with young adults from 18 to 29 years of age who were diagnosed
      with depression. Two models of psychotherapy were used: Cognitive Behavioral
      Therapy (CBT) and Narrative Cognitive Therapy (NCT). Biological rhythm was
      assessed with the Biological Rhythm Interview of Assessment in Neuropsychiatry
      (BRIAN). Severity of depressive and anxious symptoms was assessed by the Hamilton
      Depression Rating Scale (HDRS) and the Hamilton Anxiety Rating Scale (HARS),
      respectively. The sample included 97 patients who were divided within the
      protocols of psychotherapy. RESULTS: There was a significant reduction in
      depressive and anxious symptoms (p<0.001) and an increase on regulation of
      biological rhythm (p<0.05) at the twelve-month follow-up. Moreover, we showed a
      positive correlation between the reduction of depressive symptoms and regulation
      of biological rhythm (r=0.638; p<0.001) and between the reduction of anxious
      symptoms and regulation of biological rhythm (r=0.438; p<0.001). CONCLUSION: Both
      models showed that cognitive therapy was effective on the reduction of depressive
      and anxious symptoms and on the regulation of biological rhythm at a twelve-month
      follow-up evaluation. This study highlights the association between biological
      rhythm and symptoms of depression and anxiety. LIMITATION: We did not assess
      genetic, hormonal or neurochemical factors and we did not include patients under
      pharmaceutical treatment or those with severe symptomatology.

PMID- 26300330
TI  - Nicotinic acid inhibits vascular inflammation via the SIRT1-dependent signaling
      pathway.
AB  - Nicotinic acid (NA) has recently been shown to inhibit inflammatory response in
      cardiovascular disease. Sirtuin1 (SIRT1), a NAD(+)-dependent class III histone
      deacetylase, participates in the regulation of cellular inflammation. We
      hypothesized that dietary supplementation of NA could attenuate vascular
      inflammation via modulation of SIRT1 pathway. New Zealand White rabbits received
      chow or chow supplemented with 0.6% (wt/wt) NA for 2 weeks. Acute vascular
      inflammation was induced in the animals by placing a non-occlusive silastic
      collar around the left common carotid artery. At 24 h after collar implantation,
      the collar-induced production of C-reactive protein and monocyte chemotactic
      protein-1 was significantly suppressed in the NA-supplemented animals. Meanwhile,
      NA also decreased the expression of cluster of differentiation 40 (CD40) and CD40
      ligand, but up-regulated SIRT1 expression, both in rabbits and in
      lipopolysaccharide-stimulated endothelial cells. Moreover, knockdown of SIRT1
      reversed the inhibitory effect of NA on CD40 expression. Further study revealed
      that NA also decreased the expression of CD40 partly through mammalian target of
      rapamycin. These results indicate that NA protects against vascular inflammation
      via the SIRT1/CD40-dependent signaling pathway. 

PMID- 26300332
TI  - Adsorption properties of trifluoroacetic acid on anatase (101) and (001)
      surfaces: a density functional theory study.
AB  - The interaction of trifluoroacetic acid with anatase TiO2(101) and TiO2(001)
      surfaces has been studied by means of periodic density functional theory based
      calculations. On the former, the interaction is weak with the adsorbed molecules
      in a configuration almost indistinguishable from the gas phase structure. On the
      latter, the interaction is very strong; the molecule adsorbs as trifluoroacetate
      and releases a proton that binds an oxygen surface atom with a significant
      distortion of the substrate. The difference in adsorption the mode and strength
      can be understood from the different structural features of both surfaces and
      provides arguments to the role of trifluoroacetic as a morphological control
      agent in the solvothermal synthesis of TiO2 nanoparticles with predominant (001)
      facets. This, in turn, has a very significant impact on industrial production
      strategies of value-added TiO2 for photocatalytic applications. Analysis of
      calculated core level binding energies for F(1s) confirms the experimental
      assignment to F at the surface as F(-) at Ti surface sites and to F in -CF3
      groups of the adsorbed molecule. 

PMID- 26300331
TI  - Decaffeinated green tea extract rich in epigallocatechin-3-gallate prevents fatty
      liver disease by increased activities of mitochondrial respiratory chain
      complexes in diet-induced obesity mice.
AB  - Nonalcoholic fatty liver disease has been considered the hepatic manifestation of
      obesity. It is unclear whether supplementation with green tea extract rich in
      epigallocatechin-3-gallate (EGCG) influences the activity of mitochondrial
      respiratory chain complexes and insulin resistance in the liver. EGCG regulated
      hepatic mitochondrial respiratory chain complexes and was capable of improving
      lipid metabolism, attenuating insulin resistance in obese mice. Mice were divided
      into four groups: control diet+water (CW) or EGCG (CE) and hyperlipidic
      diet+water (HFW) or EGCG (HFE). All animals received water and diets ad libitum
      for 16 weeks. Placebo groups received water (0.1 ml/day) and EGCG groups (0.1 ml
      EGCG and 50 mg/kg/day) by gavage. Cytokines concentrations were obtained by
      ELISA, protein expression through Western blotting and mitochondrial complex
      enzymatic activity by colorimetric assay of substrate degradation. HFW increased
      body weight gain, adiposity index, retroperitoneal and mesenteric adipose tissue
      relative weight, serum glucose, insulin and Homeostasis Model Assessment of Basal
      Insulin Resistance (HOMA-IR); glucose intolerance was observed in oral glucose
      tolerance test (OGTT) as well as ectopic fat liver deposition. HFE group
      decreased body weight gain, retroperitoneal and mesenteric adipose tissue
      relative weight, HOMA-IR, insulin levels and liver fat accumulation; increased
      complexes II-III and IV and malate dehydrogenase activities and improvement in
      glucose uptake in OGTT and insulin sensitivity by increased protein expression of
      total AKT, IRalpha and IRS1. We did not find alterations in inflammatory
      parameters analyzed. EGCG was able to prevent obesity stimulating the
      mitochondrial complex chain, increasing energy expenditure, particularly from the
      oxidation of lipid substrates, thereby contributing to the prevention of hepatic
      steatosis and improved insulin sensitivity.

PMID- 26300333
TI  - In vitro degradation and in vivo resorption of dicalcium phosphate cement based
      grafts.
AB  - There are two types of DCP: dihydrated (brushite) and anhydrous (monetite). After
      implantation, brushite converts to hydroxyapatite (HA) which resorbs very slowly.
      This conversion is not observed after implantation of monetite cements and result
      in a greater of resorption. The precise mechanisms of resorption and degradation
      however of these ceramics remain uncertain. This study was designed to
      investigate the effect of: porosity, surface area and hydration on in vitro
      degradation and in vivo resorption of DCP. Brushite and two types of monetite
      cement based grafts (produced by wet and dry thermal conversion) were aged in
      phosphate buffered saline (PBS) and bovine serum solutions in vitro and were
      implanted subcutaneously in rats. Here we show that for high relative porosity
      grafts (50-65%), solubility and surface area does not play a significant role
      towards in vitro mass loss with disintegration and fragmentation being the main
      factors dictating mass loss. For grafts having lower relative porosity (35-45%),
      solubility plays a more crucial role in mass loss during in vitro ageing and in
      vivo resorption. Also, serum inhibited dissolution and the formation of HA in
      brushite cements. However, when aged in PBS, brushite undergoes phase conversion
      to a mixture of octacalcium phosphate (OCP) and HA. This phase conversion was not
      observed for monetite upon ageing (in both serum and PBS) or in subcutaneous
      implantation. This study provides greater understanding of the degradation and
      resorption process of DCP based grafts, allowing us to prepare bone replacement
      materials with more predictable resorption profiles. 

PMID- 26300334
TI  - Single-cell mechanics--An experimental-computational method for quantifying the
      membrane-cytoskeleton elasticity of cells.
AB  - The membrane-cytoskeleton system plays a major role in cell adhesion, growth,
      migration, and differentiation. F-actin filaments, cross-linkers, binding
      proteins that bundle F-actin filaments to form the actin cytoskeleton, and
      integrins that connect the actin cytoskeleton network to the cell plasma membrane
      and extracellular matrix are major cytoskeleton constituents. Thus, the cell
      cytoskeleton is a complex composite that can assume different shapes. Atomic
      force microscopy (AFM)-based techniques have been used to measure cytoskeleton
      material properties without much attention to cell shape. A recently developed
      surface chemical patterning method for long-term single-cell culture was used to
      seed individual cells on circular patterns. A continuum-based cell model, which
      uses as input the force-displacement response obtained with a modified AFM setup
      and relates the membrane-cytoskeleton elastic behavior to the cell geometry,
      while treating all other subcellular components suspended in the cytoplasmic
      liquid (gel) as an incompressible fluid, is presented and validated by
      experimental results. The developed analytical-experimental methodology
      establishes a framework for quantifying the membrane-cytoskeleton elasticity of
      live cells. This capability may have immense implications in cell biology,
      particularly in studies seeking to establish correlations between membrane
      cytoskeleton elasticity and cell disease, mortality, differentiation, and
      migration, and provide insight into cell infiltration through nonwoven fibrous
      scaffolds. The present method can be further extended to analyze membrane
      cytoskeleton viscoelasticity, examine the role of other subcellular components
      (e.g., nucleus envelope) in cell elasticity, and elucidate the effects of
      mechanical stimuli on cell differentiation and motility. STATEMENT OF
      SIGNIFICANCE: This is the first study to decouple the membrane-cytoskeleton
      elasticity from cell stiffness and introduce an effective approach for measuring
      the elastic modulus. The novelty of this study is the development of new
      technology for quantifying the elastic stiffness of the membrane-cytoskeleton
      system of cells. This capability could have immense implications in cell biology,
      particularly in establishing correlations between various cell diseases,
      mortality, and differentiation with membrane-cytoskeleton elasticity, examining
      through-tissue cell migration, and understanding cell infiltration in porous
      scaffolds. The present method can be further extended to analyze membrane
      cytoskeleton viscous behavior, identify the contribution of other subcellular
      components (e.g., nucleus envelope) to load sharing, and elucidate
      mechanotransduction effects due to repetitive compressive loading and unloading
      on cell differentiation and motility.

PMID- 26300335
TI  - Intracellular delivery and antitumor effects of a redox-responsive polymeric
      paclitaxel conjugate based on hyaluronic acid.
AB  - Polymer-drug conjugates have demonstrated application potentials in optimizing
      chemotherapeutics. In this study a new bioconjugate, HA-ss-PTX, was designed and
      synthesized with cooperative dual characteristics of active tumor targeting and
      selective intracellular drug release. Paclitaxel (PTX) was covalently attached to
      hyaluronic acid (HA) with various sizes (MW 9.5, 35, 770 kDa); a cross-linker
      containing disulfide bond was also used to shield drug leakage in blood
      circulation and to achieve rapid drug release in tumor cells in response to
      glutathione. Incorporation of HA to the conjugate enhanced the capabilities of
      drug loading, intracellular endocytosis and tumor targeting of micelles in
      comparison to mPEG. HA molecular weight showed significant effect on properties
      and antitumor efficacy of the synthesized conjugates. Intracellular uptake of HA
      ss-PTX toward MCF-7 cells was mediated by CD44-caveolae-mediated endocytosis.
      Compared to Taxol and mPEG-ss-PTX, HA9.5-ss-PTX demonstrated improved tumor
      growth inhibition in vivo with a TIR of 83.27 +/- 5.20%. It was concluded that
      HA9.5-ss-PTX achieved rapid intracellular release of PTX and enhanced its
      therapeutic efficacy, thus providing a platform for specific drug targeting and
      controlled intracellular release in chemotherapeutics. STATEMENT OF SIGNIFICANCE:
      Polymer-drug conjugates, promising nanomedicines, still face some technical
      challenges including a lack of specific targeting and rapid intracellular drug
      release at the target site. In this manuscript we designed and constructed a
      novel bioconjugate HA-ss-PTX, which possessed coordinated dual characteristics of
      active tumor targeting and selective intracellular drug release. Redox-responsive
      disulfide bond was introduced to the conjugate to shield drug leakage in blood
      circulation and to achieve rapid drug release at tumor site in response to
      reductant like glutathione. Paclitaxel was selected as a model drug to be
      covalently attached to hyaluronic acid (HA) with various sizes to elucidate the
      structure-activity relationship and to address whether HA could substitute PEG as
      a carrier for polymeric conjugates. Based on a series of in vitro and in vivo
      experiments, HA-ss-PTX performed well in drug loading, cellular internalization,
      tumor targeting by entering tumor cells via CD44-caveolae-mediated endocytosis
      and rapidly release drug at target in the presence of GSH. One of the key issues
      in clinical oncology is to enhance drug delivery efficacy while minimizing side
      effects. The study indicated that this new polymeric conjugate system would be
      useful in delivering anticancer agents to improve therapeutic efficacy and to
      minimize adverse effects, thus providing a platform for specific drug targeting
      and controlled intracellular release in chemotherapeutics.

PMID- 26300336
TI  - Compressed sensing traction force microscopy.
AB  - Adherent cells exert traction forces on their substrate, and these forces play
      important roles in biological functions such as mechanosensing, cell
      differentiation and cancer invasion. The method of choice to assess these active
      forces is traction force microscopy (TFM). Despite recent advances, TFM remains
      highly sensitive to measurement noise and exhibits limited spatial resolution. To
      improve the resolution and noise robustness of TFM, here we adapt techniques from
      compressed sensing (CS) to the reconstruction of the traction field from the
      substrate displacement field. CS enables the recovery of sparse signals at higher
      resolution from lower resolution data. Focal adhesions (FAs) of adherent cells
      are spatially sparse implying that traction fields are also sparse. Here we show,
      by simulation and by experiment, that the CS approach enables circumventing the
      Nyquist-Shannon sampling theorem to faithfully reconstruct the traction field at
      a higher resolution than that of the displacement field. This allows reaching
      state-of-the-art resolution using only a medium magnification objective. We also
      find that CS improves reconstruction quality in the presence of noise. STATEMENT
      OF SIGNIFICANCE: A great scientific advance of the past decade is the recognition
      that physical forces determine an increasing list of biological processes.
      Traction force microscopy which measures the forces that cells exert on their
      surroundings has seen significant recent improvements, however the technique
      remains sensitive to measurement noise and severely limited in spatial
      resolution. We exploit the fact that the force fields are sparse to boost the
      spatial resolution and noise robustness by applying ideas from compressed
      sensing. The novel method allows high resolution on a larger field of view. This
      may in turn allow better understanding of the cell forces at the multicellular
      level, which are known to be important in wound healing and cancer invasion.

PMID- 26300337
TI  - The pre-vascularisation of a collagen-chondroitin sulphate scaffold using human
      amniotic fluid-derived stem cells to enhance and stabilise endothelial cell
      mediated vessel formation.
AB  - A major problem in tissue engineering (TE) is graft failure in vivo due to core
      degradation in in vitro engineered constructs designed to regenerate thick
      tissues such as bone. The integration of constructs post-implantation relies on
      the rapid formation of functional vasculature. A recent approach to overcome core
      degradation focuses on the creation of cell-based, pre-engineered vasculature
      formed within the TE construct in vitro, prior to implantation in vivo. The
      primary objective of this study was to investigate whether an amniotic fluid
      derived stem cell (AFSC)-human umbilical vein endothelial cell (HUVEC) co-culture
      could be used to engineer in vitro vasculature in a collagen chondroitin sulphate
      (CCS) scaffold. The secondary objective was to investigate whether hypoxic
      conditions (2% O2) could enhance microcapillary-like structure formation by this
      co-culture. The results of this study demonstrate, for the first time, that the
      AFSC-HUVEC co-culture was capable of pre-vascularising CCS scaffolds within 7
      days and that the AFSCs are capable of behaving as pericytes while interacting
      with HUVECS to form microcapillary-like structures. However, this microcapillary
      like structure formation was reduced in hypoxic conditions. qRT-PCR analysis
      indicated that an upregulation of VEGFR1 and accompanying decrease of VEGFR2 gene
      expression may be responsible for the poor response of these microcapillary-like
      structures to hypoxic conditions. Overall, however, these results demonstrate the
      potential of this newly developed co-culture system for the formation of pre
      engineered vasculature within TE constructs. STATEMENT OF SIGNIFICANCE: This
      article describes the development of an amniotic fluid-derived stem cell (AFSC)
      human umbilical vein endothelial cell (HUVEC) co-culture for use in engineering
      in vitro vasculature in a collagen chondroitin sulphate (CCS) scaffold. The
      article also describes the effect of hypoxic conditions on the networks of
      microcapillary-like structures formed by this co-culture. The AFSC-HUVEC co
      culture was capable of pre-vascularising CCS scaffolds within 7 days. However,
      microcapillary-like structure formation was reduced in hypoxic conditions.
      Overall, these results demonstrate the potential of this newly developed co
      culture system for the formation of pre-engineered vasculature within TE
      constructs. The proangiogenic nature of this co-culture has the potential to both
      enhance bone regeneration while also overcoming the problem of inadequate
      vascularisation of grafts commonly seen in the field of tissue engineering.

PMID- 26300338
TI  - Elementary School Children's Reasoning About Social Class: A Mixed-Methods Study.
AB  - The current study examined children's identification and reasoning about their
      subjective social status (SSS), their beliefs about social class groups (i.e.,
      the poor, middle class, and rich), and the associations between the two. Study
      participants were 117 10- to 12-year-old children of diverse racial, ethnic, and
      socioeconomic backgrounds attending a laboratory elementary school in Southern
      California. Results indicated that children's SSS ratings correlated with
      indicators of family socioeconomic status and were informed by material
      possessions, lifestyle characteristics, and social and societal comparisons.
      Children rated the poor as having fewer positive attributes and more negative
      attributes than the middle class, and fewer positive attributes than the rich.
      Lower SSS children held less positive attitudes toward the poor than children
      with middle SSS ratings.

PMID- 26300340
TI  - Community Context and Men's Control-Seeking in Intimate Relationships.
AB  - This study explores social-ecological influences on men's control-seeking in
      intimate relationships with women. Desire for control is central to the battered
      women's movement and is incorporated into intimate partner violence (IPV)
      prevention work. Recent IPV scholarship re-focuses on control, but the role of
      community contexts is underdeveloped. Community contexts have been associated
      with men's risk for IPV and evidence supports that social ecology facilitates IPV
      against women. Given the importance of the social ecology to control in IPV, this
      study examines community contexts that influence men's control-seeking of women
      partners. The sample comprised 2,342 in-state, male undergraduate students who
      completed a cross-sectional survey at a public university. Hypotheses were tested
      using hierarchical linear modeling. Results support a connection between county
      contexts and men's control-seeking toward women partners. Implications for IPV
      research and practice are discussed.

PMID- 26300341
TI  - Genetic transmission of reading ability.
AB  - Reading is the processing of written language. Family resemblance for reading
      (dis)ability might be due to transmission of a genetic liability or due to family
      environment, including cultural transmission from parents to offspring. Familial
      risk studies exploring neurobehavioral precursors for dyslexia and twin studies
      can only speak to some of these issues, but a combined twin-family study can
      resolve the nature of the transmitted risk. Word-reading fluency scores of 1100
      participants from 431 families (with twins, siblings and their parents) were
      analyzed to estimate genetic and environmental sources of variance, and to test
      the presence of assortative mating and cultural transmission. Results show that
      variation in reading ability is mainly caused by additive and non-additive
      genetic factors (64%). The substantial assortative mating (rfather-mother=0.38)
      has scientific and clinical implications. We conclude that parents and offspring
      tend to resemble each other for genetic reasons, and not due to cultural
      transmission.

PMID- 26300339
TI  - Cardiolipin Interactions with Proteins.
AB  - Cardiolipins (CL) represent unique phospholipids of bacteria and eukaryotic
      mitochondria with four acyl chains and two phosphate groups that have been
      implicated in numerous functions from energy metabolism to apoptosis. Many
      proteins are known to interact with CL, and several cocrystal structures of
      protein-CL complexes exist. In this work, we describe the collection of the first
      systematic and, to the best of our knowledge, the comprehensive gold standard
      data set of all known CL-binding proteins. There are 62 proteins in this data
      set, 21 of which have nonredundant crystal structures with bound CL molecules
      available. Using binding patch analysis of amino acid frequencies, secondary
      structures and loop supersecondary structures considering phosphate and acyl
      chain binding regions together and separately, we gained a detailed understanding
      of the general structural and dynamic features involved in CL binding to
      proteins. Exhaustive docking of CL to all known structures of proteins
      experimentally shown to interact with CL demonstrated the validity of the docking
      approach, and provides a rich source of information for experimentalists who may
      wish to validate predictions. 

PMID- 26300342
TI  - Post-radiotherapy hypothyroidism in dogs treated for thyroid carcinomas.
AB  - Hypothyroidism is a common adverse event after head and neck radiotherapy in
      human medicine, but uncommonly reported in canine patients. Records of 21 dogs
      with histologically or cytologically confirmed thyroid carcinoma receiving
      definitive or hypofractionated radiotherapy were reviewed. Nine cases received 48
      Gy in 12 fractions, 10 received 36 Gy in 4 fractions and 2 received 32 Gy in 4
      fractions. Seventeen cases had radiotherapy in a post-operative setting. Ten
      cases developed hypothyroidism (47.6%) after radiotherapy. The development of
      hypothyroidism was not associated with the radiotherapy protocol used. Median
      time to diagnosis of hypothyroidism was 6 months (range, 1-13 months).
      Hypothyroidism is a common side effect following radiotherapy for thyroid
      carcinomas. Monitoring of thyroid function following radiotherapy is recommended.
      No specific risk factors have been identified.

PMID- 26300343
TI  - The surface plasmon resonance effect on the enhancement of photodegradation
      activity by Au/ZnSn(OH)6 nanocubes.
AB  - We demonstrated Au/ZnSn(OH)6 hollow nanocubes that exhibited extremely high
      photodegradation activity under ultraviolet and visible-light illumination. The
      pristine ZnSn(OH)6 hollow nanocubes can achieve a 100% photodegradation ratio
      within 20 min under ultraviolet-light illumination. The high photodegradation
      activity of ZnSn(OH)6 can be attributed to plenty of OH groups present in the
      polyhedral corner of the ZnSn(OH)6 that generate a large number of reactive
      hydroxyl radicals for degradation of dye molecules. High resolution transmission
      electron microscopy (HRTEM) and scanning electron microscopy (SEM) images
      revealed that the size of the ZnSn(OH)6 and Au/ZnSn(OH)6 hollow nanocubes is ~30
      80 nm. After ZnSn(OH)6 nanocubes were decorated with Au, the heterostructures
      exhibited a significantly strong and widened absorption peak in the range 450-750
      nm because of the surface plasmon resonance (SPR) effect, and therefore showed an
      excellent photodegradation activity under visible-light illumination. The rate
      constant k of Au/ZnSn(OH)6 is as high as 51.8 L mol(-1) min(-1) under UV-light
      illumination. This value is much higher than those reported so far. The hydroxyl
      groups essentially enhance the reaction rate and enable the active radicals to
      participate in the reaction for destruction of the Rhodamine B (RB) solution.
      Au/ZnSn(OH)6 has been successfully applied for preparing hybrid coating screens
      with polydimethylsiloxane (PDMS), which exhibited an excellent mechanical
      desirable durability and extended its feasible application in our daily lives. 

PMID- 26300344
TI  - LIM-only protein FHL2 regulates experimental pulmonary Schistosoma mansoni egg
      granuloma formation.
AB  - LIM-only protein FHL2 is associated with several immune and inflammatory diseases
      such as arthritis, influenza A virus infection, and lung inflammation. However,
      the role of FHL2 in macrophage differentiation and in the development of
      granuloma formation is unknown. Here, we show that expression of FHL2 is induced
      in mouse bone marrow derived macrophages (BMMs) following stimulation with M2
      cytokines such as IL-4 and IL-10. FHL2-knockout (FHL2-KO) BMMs exhibit a
      proinflammatory M1 phenotype after LPS treatment and display a reduced anti
      inflammatory M2 phenotype following IL-4 treatment. Furthermore, thioglycollate
      induced migration of macrophages and B cells is enhanced in FHL2-KO mice. To
      evaluate the importance of FHL2 in the development of pulmonary granuloma
      formation, FHL2-KO mice were challenged with Schistosoma mansoni eggs. FHL2-KO
      mice show an enhanced number of granulomas and display decreased expression of
      Th2 markers and an exacerbated Th1 type of inflammation, characterized by
      enhanced expression of neutrophil markers and Th1 cytokines. Furthermore, the
      expression of barrier proteins is reduced in FHL2-KO lung compared to WT.
      Collectively, these data identify a previously unrecognized role for FHL2 in the
      pathogenesis of pulmonary granulomatous inflammation, partly through its effect
      on macrophage polarization, modulation of the Th1/Th2 balance and regulation of
      permeability in lung. 

PMID- 26300345
TI  - A Caged Ret Kinase Inhibitor and its Effect on Motoneuron Development in
      Zebrafish Embryos.
AB  - Proto-oncogene tyrosine-protein kinase receptor RET is implicated in the
      development and maintenance of neurons of the central and peripheral nervous
      systems. Attaching activity-compromising photocleavable groups (caging) to
      inhibitors could allow for external spatiotemporally controlled inhibition using
      light, potentially providing novel information on how these kinase receptors are
      involved in cellular processes. Here, caged RET inhibitors were obtained from 3
      substituted pyrazolopyrimidine-based compounds by attaching photolabile groups to
      the exocyclic amino function. The most promising compound displayed excellent
      inhibitory effect in cell-free, as well as live-cell assays upon decaging.
      Furthermore, inhibition could be efficiently activated with light in vivo in
      zebrafish embryos and was shown to effect motoneuron development. 

PMID- 26300346
TI  - Analysis of proliferation and apoptotic induction by 20 steroid glycosides in
      143B osteosarcoma cells in vitro.
AB  - OBJECTIVES: Osteosarcoma is the most common type of malignant bone tumour in
      children and adolescents; it has poor prognosis, is highly metastatic and is
      resistant to current therapeutic approaches. In this study, different herbal
      extracts used in phytotherapy have been screened after searching innovative
      natural anti-cancer components. MATERIALS AND METHODS: Twenty steroid glycosides
      were examined for accordance to their potential of inhibiting cell proliferation
      and inducing apoptosis in the osteosarcoma cell line 143B. Cell proliferation was
      examined using a CASY counter. Effects of cardiac glycosides on induction of
      apoptosis were evaluated by Annexin V-APC and flow cytometry, caspase activity
      assay and measurement of mitochondrial membrane potential. RESULTS: The study
      revealed that various steroid glycosides suppress cell proliferation in a
      concentration-dependent manner. Further investigations indicated apoptotic
      induction by 17 of the 20 tested cardenolides and bufadienolides. Bufadienolide
      proscillaridin A, arenobufagin, and cardenolides evomonoside, convallatoxol and
      ouabain waged strongest apoptotic induction, associated with breakdown of
      mitochondrial membrane potential and activation of caspases -8 and -9. In
      contrast, the bufadienolide resibufogenin and cardenolide uzarin had no effect on
      proliferation inhibition, apoptotic induction or change in mitochondrial membrane
      potential. CONCLUSION: These results indicate that bufadienolides proscillaridin
      A and arenobufagin and cardenolide evomonoside, or related natural compounds
      might be promising new starting points for development of novel anti-cancer
      agents for treatment of osteosarcoma.

PMID- 26300347
TI  - Effects of acrosomal conditions of frozen-thawed spermatozoa on the results of
      artificial insemination in Japanese Black cattle.
AB  - The purposes of this study were to examine the relationship between male
      artificial insemination (AI) fertility and sperm acrosomal conditions assessed by
      new and conventional staining techniques and to identify possible reproductive
      dysfunctions causing low conception rates in AI using frozen-thawed spermatozoa
      with poor acrosomal conditions in Japanese Black bulls. We investigated
      individual differences among bulls in the results concerning (1) acrosomal
      conditions of frozen-thawed spermatozoa as assessed by not merely peanut
      agglutinin-lectin staining (a conventional staining technique) but also
      immunostaining of acrosomal tyrosine-phosphorylated proteins (a new staining
      technique), (2) routine AI using frozen-thawed spermatozoa as assessed by
      pregnancy diagnosis, (3) in vivo fertilization of frozen-thawed spermatozoa and
      early development of fertilized eggs as assessed by superovulation/AI-embryo
      collection tests and (4) in vitro fertilization of frozen-thawed spermatozoa with
      oocytes. The percentages of frozen-thawed spermatozoa with normal acrosomal
      conditions assessed by the abovementioned staining techniques were significantly
      correlated with the conception rates of routine AI, rates of transferable embryos
      in superovulation/AI-embryo collection tests and in vitro fertilization rates.
      These results are consistent with new suggestions that the distribution of
      acrosomal tyrosine-phosphorylated proteins as well as the acrosomal morphology of
      frozen-thawed spermatozoa are AI fertility-associated markers that are valid for
      the prediction of AI results and that low conception rates in AI using frozen
      thawed spermatozoa with poor acrosomal conditions result from reproductive
      dysfunctions in the processes between sperm insemination into females and early
      embryo development, probably failed fertilization of frozen-thawed spermatozoa
      with oocytes.

PMID- 26300348
TI  - Stable polymyxin B susceptibility among carbapenem-resistant Acinetobacter
      baumannii: for how long?

PMID- 26300349
TI  - Naringin ameliorates cognitive deficits via oxidative stress, proinflammatory
      factors and the PPARgamma signaling pathway in a type 2 diabetic rat model.
AB  - Naringenin is a flavonoid polyphenolic compound, which facilitates the removal of
      free radicals, oxidative stress and inflammation. The present study aimed to
      obtain a better understanding of the effects of curcumin on the regulation of
      diabetes-associated cognitive decline, and its underlying mechanisms. An
      experimental diabetes mellitus (DM) rat model was induced by streptozoticin (50
      mg/kg). Following treatment with naringin (100 and 200 mg/kg) for 16 weeks, the
      body weight and blood glucose levels of the DM rats were measured. A morris water
      maze test was used to analyze the effects of naringin on the cognitive deficit of
      the DM rats. The levels of oxidative stress, proinflammatory factors, caspase-3
      and caspase-9, and the protein expression of peroxisome proliferator-activated
      receptor gamma (PPARgamma) were quantified in the DM rats using a commercially
      available kit and western blot assay, respectively. In addition, a GW9662
      PPARgamma inhibitor (0.3 mg/kg) was administered to the DM rats to determine
      whether PPARgamma affected the effects of naringin on the cognitive deficit of
      the DM rats. The results demonstrated that naringin increased the body weight,
      blood glucose levels, and cognitive deficits of the DM rats. The levels of
      oxidative stress and proinflammatory factors in the naringin-treated rats were
      significantly lower, compared with those of the DM rats. In addition, naringin
      activated the protein expression of PPARgamma, and administration of the
      PPARgamma inhibitor decreased the protein expression of PPARgamma, and attenuated
      the effects of naringin on cognitive deficit. The results also demonstrated that
      naringin decreased the expression levels of caspase-3 and caspase-9 in the DM
      rats. These results suggested that naringin ameliorated cognitive deficits via
      oxidative stress, proinflammatory factors and the PPARgamma signaling pathway in
      the type 2 diabetic rat model. Furthermore, oxidative stress, proinflammatory
      factors and PPARgamma signaling may be involved in mediating these effects.

PMID- 26300350
TI  - Polybrominated diphenyl ethers, organochlorine pesticides, and polycyclic
      aromatic hydrocarbons in water from the Jiulong River Estuary, China: levels,
      distributions, influencing factors, and risk assessment.
AB  - Estuarine systems play an important role in the transportation and transformation
      of organic pollutants from rivers. Polybrominated diphenyl ether (PBDE),
      organochlorine pesticide (OCP), and polycyclic aromatic hydrocarbon (PAH)
      concentrations in water of the Jiulong River Estuary (JRE), China, were
      investigated to characterize their distribution, possible source, and potential
      ecological risk as well as the influencing factors. The total concentrations of
      PBDEs, OCPs, and PAHs varied from 5.2 to 12.3 pg L-1, from 29.1 to 96.4 ng L-1,
      and from 28.6 to 48.5 ng L-1, respectively. Their compositions were all
      consistent at different stations; even the input pathways were multifarious. A
      source analysis showed that PBDEs may come from the flame retardant usages of
      penta-BDE and deca-BDE; hexachlorocyclohexane isomers (HCHs) were from the use of
      technical HCHs, while DDTs were attributed to early residuals of industrial
      sources, and PAHs were mainly from pyrolytic sources. The spatial distributions
      of PBDEs and OCPs were quite similar with their concentrations, decreasing along
      the estuary and then increasing when passing the Xiamen Harbor. PAH
      concentrations were similar along the whole estuary, suggesting that local
      sources and hydrological conditions might be the influencing factors. The
      concentrations of these pollutants changed with tidal conditions and were
      positively correlated with SPM, DOC, and chlorophyll a but negatively correlated
      with salinity. The ecological risk assessment revealed that OCPs and PAHs posed
      slightly higher potential risks to aquatic organism in the study area.

PMID- 26300352
TI  - Dry co-digestion of sewage sludge and rice straw under mesophilic and
      thermophilic anaerobic conditions.
AB  - Dry anaerobic digestion of sewage sludge can recover biogas as energy; however,
      its low C/N ratio limits it as a single substrate in the anaerobic digestion.
      Rice straw is an abundant agricultural residue in China, which is rich in carbon
      and can be used as carbon source. In the present study, the performance of dry co
      digestion of sewage sludge and rice straw was investigated under mesophilic (35 
      degrees C) and thermophilic (55  degrees C) conditions. The operational factors
      impacting dry co-digestion of sewage sludge and rice straw such as C/N ratio,
      moisture content, and initial pH were explored under mesophilic conditions. The
      results show that low C/N ratios resulted in a higher biogas production rate, but
      a lower specific biogas yield; low moisture content of 65 % resulted in the
      instability of the digestion system and a low specific biogas yield. Initial pH
      ranging 7.0-9.0 did not affect the performance of the anaerobic digestion. The
      C/N ratio of 26-29:1, moisture content of 70-80 %, and pH 7.0-9.0 resulted in
      good performance in the dry mesophilic co-digestion of sewage sludge and rice
      straw. As compared with mesophilic digestion, thermophilic co-digestion of sewage
      sludge and rice straw significantly enhanced the degradation efficiency of the
      substrates and the specific biogas yield (p < 0.05) at the conditions of C/N
      ratio 26:1, moisture content 80 %, and natural initial pH. Although high
      concentrations of ammonia-nitrogen (NH4-N, 1500 mg/kg wet weight) were formed
      during thermophilic digestion, there was no obvious inhibition occurred. The
      results indicated that rice straw can be used as carbon source for the dry co
      digestion of sewage sludge under mesophilic and thermophilic conditions.

PMID- 26300351
TI  - Geochemical characterization and heavy metal migration in a coastal polluted
      aquifer incorporating tidal effects: field investigation in Chongming Island,
      China.
AB  - The occurrence and migration of heavy metal in coastal aquifer incorporating
      tidal effects were investigated in detail by the field geological survey and
      observation. The continuous groundwater sampling, field observation (for
      groundwater potentiometric surface elevation, pH, dissolved oxygen, temperature,
      and salinity), and laboratory analysis (for Cr, Ni, Cu, Zn, Cd, and Pb
      concentration) were conducted through eight monitoring wells located around the
      landfill in the northern part of Chongming Island, China. The results showed that
      the unconfined aquifer medium was estuary-littoral facies deposit of Holocene,
      mainly gray clayey silt and grey sandy silt, and the groundwater flow was mainly
      controlled by topography condition of the aquifer formation strike. The
      background values of Cr, Ni, Cu, Zn, Cd, and Pb in Chongming Island were 3.10 +/-
      3.09, 0.81 +/- 0.25, 1.48 +/- 1.09, 43.32 +/- 33.06, 0.08 +/- 0.16, and 0.88 +/-
      1.74 MUg/L, respectively. Compared with the groundwater samples around the study
      area, the drinking water was qualified and was free from the seawater
      intrusion/estuarine facies contaminant encroachment. Pollutant discharge was
      reflected in water quality parameters, the Cr and Cu concentrations elevated to
      the peak of 50.07 and 46.00 MUg/L, respectively, and meanwhile specific migration
      regularity was embodied in observation time series as well as other elements.
      This migration regularity was not fully identical according to correlations
      between these analyzed elements. Ambient watery environment, anthropogenic
      disturbance, regional hydrogeological condition, and biogeochemical reactivity on
      heavy metals reduced/altered the significance of elements correlation in the
      migration pathway in coastal aquifer.

PMID- 26300353
TI  - Accuracy and uncertainty analysis of soil Bbf spatial distribution estimation at
      a coking plant-contaminated site based on normalization geostatistical
      technologies.
AB  - Data distribution is usually skewed severely by the presence of hot spots in
      contaminated sites. This causes difficulties for accurate geostatistical data
      transformation. Three types of typical normal distribution transformation methods
      termed the normal score, Johnson, and Box-Cox transformations were applied to
      compare the effects of spatial interpolation with normal distribution
      transformation data of benzo(b)fluoranthene in a large-scale coking plant
      contaminated site in north China. Three normal transformation methods decreased
      the skewness and kurtosis of the benzo(b)fluoranthene, and all the transformed
      data passed the Kolmogorov-Smirnov test threshold. Cross validation showed that
      Johnson ordinary kriging has a minimum root-mean-square error of 1.17 and a mean
      error of 0.19, which was more accurate than the other two models. The area with
      fewer sampling points and that with high levels of contamination showed the
      largest prediction standard errors based on the Johnson ordinary kriging
      prediction map. We introduce an ideal normal transformation method prior to
      geostatistical estimation for severely skewed data, which enhances the
      reliability of risk estimation and improves the accuracy for determination of
      remediation boundaries. 

PMID- 26300354
TI  - Estrogenicity and androgenicity screening of PCB sulfate monoesters in human
      breast cancer MCF-7 cells.
AB  - Recent studies identified polychlorinated biphenyl (PCB) sulfate esters as a
      major product of PCB metabolism. Since hydroxy-PCBs (HO-PCBs), the immediate
      precursors of PCB sulfates and important contributors to PCB toxicity, were shown
      to have estrogenic activity, we investigated the estrogenicity/androgenicty of a
      series of PCB sulfate metabolites. We synthesized the five possible structural
      sulfate monoester metabolites of PCB 3, a congener shown to be biotransformed to
      sulfates, a sulfate ester of the paint-specific congener PCB 11, and sulfate
      monoesters of two HO-PCBs reported to interact with sulfotransferases (PCB 39, no
      ortho chlorines, and PCB 53, 3 ortho chlorines). We tested these PCB sulfates and
      4'-HO-PCB 3 as positive control for estrogenic, androgenic, anti-estrogenic, and
      anti-androgenic activity in the E- and A-screen with human breast cancer MCF7
      derived cells at 100 MUM-1 pM concentrations. Only 4'-HO-PCB 3 was highly
      cytotoxic at 100 MUM. We observed structure-activity relationships: compounds
      with a sulfate group in the chlorine-containing ring of PCB 3 (2PCB 3 and 3PCB 3
      sulfate) showed no interaction with the estrogen (ER) and androgen (AR) receptor.
      The 4'-HO-PCB 3 and its sulfate ester had the highest estrogenic effect, but at
      100-fold different concentrations, i.e., 1 and 100 MUM, respectively. Four of the
      PCB sulfates were estrogenic (2'PCB 3, 4'PCB 3, 4'PCB 39, and 4'PCB 53 sulfates;
      at 100 MUM). These sulfates and 3'PCB 3 sulfate also exhibited anti-estrogenic
      activity, but at nM and pM concentrations. The 4'PCB 3 sulfate (para-para'
      substituted) had the strongest androgenic activity, followed by 3'PCB 3, 4'PCB
      53, 4PCB11, and 4PCB 39 sulfates and the 4'HO-PCB 3. In contrast, anti
      androgenicity was only observed with the two compounds that have the sulfate
      group in ortho- or meta- position in the second ring (2'PCB 3 and 3'PCB 3
      sulfate). No dose-response was observed in any screen, but, with exception of
      estrogenic activity (only seen at 100 MUM), endocrine activity was often
      displayed at several concentrations and even at 1 pM concentration. These data
      suggest that sulfation of HO-PCBs is indeed reducing their cytotoxicity and
      estrogenicity, but may produce other endocrine disruptive activities at very low
      concentrations.

PMID- 26300355
TI  - Comparison of Cr(VI) removal by activated sludge and dissolved organic matter
      (DOM): importance of UV light.
AB  - Removal of toxic Cr(VI) by activated sludge and DOM derived from activated sludge
      was investigated in this study. A rapid increase in TOC concentration from 50.93
      to 127.40 mg L(-1) is observed during the Cr(VI) removal process by activated
      sludge in the pH range of 2-9. Removal efficiencies of Cr(VI) by either activated
      sludge or DOM greatly decreased with the increasing initial pH. Kinetics of
      Cr(VI) removal by activated sludge indicate that both biosorption and
      bioreduction are involved in the Cr(VI) removal. Cr(VI) removal by DOM is slow in
      dark, but it is greatly enhanced when UV light is applied. The first-order
      constant increases from 0.0033 (in dark) to 0.079 min(-1) (UV illumination) at pH
      2.0 and 1068 mg L(-1) DOM. The enhancement of Cr(VI) reduction is due to the
      generation of the reactive intermediates such as O2(?-) and DOM* as DOM absorbed
      light energy, which plays important roles in the reduction of Cr(VI).

PMID- 26300356
TI  - Modified MODFLOW-based model for simulating the agglomeration and transport of
      polymer-modified Fe0 nanoparticles in saturated porous media.
AB  - The solute transport model MODFLOW has become a standard tool in risk assessment
      and remediation design. However, particle transport models that take into account
      both particle agglomeration and deposition phenomena are far less developed. The
      main objective of the present study was to evaluate the feasibility of adapting
      the standard code MODFLOW/MT3D to simulate the agglomeration and transport of
      three different types of polymer-modified nanoscale zerovalent iron (NZVI) in one
      dimensional (1-D) and two-dimensional (2-D) saturated porous media. A first-order
      decay of the particle population was used to account for the agglomeration of
      particles. An iterative technique was used to optimize the model parameters. The
      model provided good matches to 1-D NZVI-breakthrough data sets, with R 2 values
      ranging from 0.96 to 0.99, and mass recovery differences between the experimental
      results and simulations ranged from 0.1 to 1.8 %. Similarly, simulations of NZVI
      transport in the heterogeneous 2-D model demonstrated that the model can be
      applied to more complicated heterogeneous domains. However, the fits were less
      good, with the R 2 values in the 2-D modeling cases ranging from 0.75 to 0.95,
      while the mass recovery differences ranged from 0.7 to 6.5 %. Nevertheless, the
      predicted NZVI concentration contours during transport were in good agreement
      with the 2-D experimental observations. The model provides insights into NZVI
      transport in porous media by mathematically decoupling agglomeration, attachment,
      and detachment, and it illustrates the importance of each phenomenon in various
      situations. Graphical Abstract ?.

PMID- 26300357
TI  - Influences of humic acid and fulvic acid on horizontal leaching behavior of
      anthracene in soil barriers.
AB  - The influences of humic acid (HA) and fulvic acid (FA) on horizontal leaching
      behaviors of anthracene in barriers were investigated. Soil colloids (<=1 MUm)
      were of concern because of their abilities of colloid-facilitated transport for
      hydrophobic organic compounds with soluble and insoluble organic matters. Through
      freely out of the barriers in the presence of soil colloids with FA added, the
      higher concentrations of anthracene were from 320 MUg L(-1) (D1 and D3) to 390
      MUg L(-1) (D2 and D4) with 1 to 20 cm in length. The contents of anthracene were
      distributed evenly at 25 ng g(-1) dry weight (DW) (D1 and D3) and 11 ng g(-1) DW
      (D2 and D4) in barriers. Therefore, anthracene leaching behaviors were mainly
      induced by soil colloids with soluble organic matters. The insoluble organic
      matters would facilitate anthracene onto soil colloids and enhance the movement
      in and through porous media of soil matrix.

PMID- 26300358
TI  - Human and animal enteric virus in groundwater from deep wells, and recreational
      and network water.
AB  - This study was designed to assess the presence of human adenovirus (HAdV),
      rotavirus-A (RVA), hepatitis A virus (HAV), and porcine circovirus-2 (PCV2) in
      groundwater from deep wells, and recreational and network waters. The water
      samples were collected and concentrated and the virus genomes were assessed and
      quantified by quantitative PCR (qPCR). Infectious HAdV was evaluated in
      groundwater and network water samples by integrated cell culture using
      transcribed messenger RNA (mRNA) (ICC-RT-qPCR). In recreational water samples,
      HAdV was detected in 100 % (6/6), HAV in 66.6 % (4/6), and RVA in 66.6 % (4/6).
      In network water, HAdV was detected in 100 % (6/6) of the samples (these 83 %
      contained infectious HAdV), although HAV and RVA were not detected and PCV2 was
      not evaluated. In groundwater from deep wells, during rainy period, HAdV and RVA
      were detected in 80 % (4/5) of the samples, and HAV and PCV2 were not detected;
      however, during dry period, HAdV and RVA were detected in 60 % (3/5), HAV in only
      one sample, and PCV2 in 60 % (4/5). In groundwater, all samples contained
      infectious HAdV. PCV2 presence in groundwater is indicative of contamination
      caused by swine manure in Concordia, Santa Catarina, Brazil. The disinfection of
      human and animal wastes is urgent, since they can contaminate surface and
      groundwater, being a potential threat for public and animal health.

PMID- 26300359
TI  - Long-term passive restoration following fluvial deposition of sulphidic copper
      tailings: nature filters out the solutions.
AB  - Despite the growing popularity of ecological restoration approach, data on
      primary succession on toxic post-mining substrates, under site environmental
      conditions which considerably differ from the surrounding environment, are still
      scarce. Here, we studied the spontaneous vegetation development on an unusual
      locality created by long-term and large-scale fluvial deposition of sulphidic
      tailings from a copper mine in a pronouncedly xerothermic, calcareous
      surrounding. We performed multivariate analyses of soil samples (20 physical and
      chemical parameters) and vegetation samples (floristic and structural parameters
      in three types of occurring forests), collected along the pollution gradients
      throughout the affected floodplain. The nature can cope with two types of imposed
      constraints: (a) excessive Cu concentrations and (b) very low pH, combined with
      nutrient deficiency. The former will still allow convergence to the original
      vegetation, while the latter will result in novel, depauperate assemblages of
      species typical for cooler and moister climate. Our results for the first time
      demonstrate that with the increasing severity of environmental filtering, the
      relative importance of the surrounding vegetation for primary succession strongly
      decreases. 

PMID- 26300360
TI  - Decomposing the trade-environment nexus for Malaysia: what do the technique,
      scale, composition, and comparative advantage effect indicate?
AB  - This paper investigates the impact of trade openness on CO2 emissions using time
      series data over the period of 1970QI-2011QIV for Malaysia. We disintegrate the
      trade effect into scale, technique, composition, and comparative advantage
      effects to check the environmental consequence of trade at four different
      transition points. To achieve the purpose, we have employed augmented Dickey
      Fuller (ADF) and Phillips-Perron (PP) unit root tests in order to examine the
      stationary properties of the variables. Later, the long-run association among the
      variables is examined by applying autoregressive distributed lag (ARDL) bounds
      testing approach to cointegration. Our results confirm the presence of
      cointegration. Further, we find that scale effect has positive and technique
      effect has negative impact on CO2 emissions after threshold income level and form
      inverted U-shaped relationship-hence validates the environmental Kuznets curve
      hypothesis. Energy consumption adds in CO2 emissions. Trade openness and
      composite effect improve environmental quality by lowering CO2 emissions. The
      comparative advantage effect increases CO2 emissions and impairs environmental
      quality. The results provide the innovative approach to see the impact of trade
      openness in four sub-dimensions of trade liberalization. Hence, this study
      attributes more comprehensive policy tool for trade economists to better design
      environmentally sustainable trade rules and agreements. 

PMID- 26300361
TI  - Removal of Pb and Zn from contaminated soil by different washing methods: the
      influence of reagents and ultrasound.
AB  - Pb and Zn contamination in agricultural soils has become an important issue for
      human health and the environment. Washing is an effective method for remediating
      polluted soil. Here, we compare several washing materials and methods in the
      treatment of Pb- and Zn-polluted farmland soil. We examined four washing
      reagents, hydrochloric acid, citric acid, Na2EDTA, and tartaric acid, all of
      which independently removed Zn at rates >65 %. Combining washing reagents
      markedly enhanced heavy metal removal, by using Na2EDTA and either tartaric acid
      or lactate in sequence: Pb and Zn removal rates improved to 84.1 and 82.1 % for
      Na2EDTA-tartaric acid; and to 88.3 and 89.9 % for Na2EDTA-lactate, respectively.
      Additionally, combining ultrasound with conventional washing methods markedly
      improved washing efficiency, by shortening washing duration by 96 %. We achieved
      similar removal rates using ultrasound for 10 min, compared with traditional
      mechanical vibration alone for 4 h. We concluded that treating Pb- and Zn
      contaminated soil with appropriate washing reagents under optimal conditions can
      greatly enhance the remediation of polluted farmland soils.

PMID- 26300362
TI  - Green synthesis of copper nanoparticles for the efficient removal (degradation)
      of dye from aqueous phase.
AB  - The present work reports the utilization of a common household waste material
      (fish scales of Labeo rohita) for the synthesis of copper nanoparticles. The
      method so developed was found to be green, environment-friendly, and economic.
      The fish scale extracts were acting as a stabilizing and reducing agents. This
      method avoids the use of external reducing and stabilizing agents, templates, and
      solvents. The compositional abundance of gelatin may be envisaged for the
      effective reductive as well as stabilizing potency. The mechanisms for the
      formation of nanoparticles have also been presented. The synthesized copper
      nanoparticles formed were predominantly spherical in nature with an average size
      of nanoparticles in the range of 25-37 nm. The copper nanoparticles showed
      characteristic Bragg's reflection planes of fcc which was supported by both
      selected area electron diffraction and X-ray diffraction pattern and showed
      surface plasmon resonance at 580 nm. Moreover, the energy dispersive spectroscopy
      pattern also revealed the presence of only elemental copper in the copper
      nanoparticles. The prepared nanoparticles were used for the remediation of a
      carcinogenic and noxious textile dye, Methylene blue, from aqueous solution.
      Approximately, 96 % degradation of Methylene blue dye was observed within 135 min
      using copper nanoparticles. The probable mechanism for the degradation of the dye
      has been presented, and the degraded intermediates have been identified using the
      liquid chromatography-mass spectroscopy technique. The high efficiency of
      nanoparticles as photocatalysts has opened a promising application for the
      removal of hazardous dye from industrial effluents contributing indirectly to
      environmental cleanup process.

PMID- 26300363
TI  - Spatial distribution, source apportionment and ecological risk assessment of
      residual organochlorine pesticides (OCPs) in the Himalayas.
AB  - The Indian Himalayan Region (IHR) is one of the important mountain ecosystems
      among the global mountain system which support wide variety of flora, fauna,
      human communities and cultural diversities. Surface soil samples collected from
      IHR were analysed for 23 organochlorine pesticides (OCPs). The concentration of
      ?OCPs ranged from 0.28 to 2143.96 ng/g (mean 221.54 ng/g) and was mostly
      dominated by DDTs. The concentration of ?DDTs ranged from 0.28 to 2126.94 ng/g
      (mean 216.65 ng/g). Other OCPs such as HCHs, endosulfan and heptachlor, Aldrin
      and dieldrin were detected in lower concentration in IHR. Their concentrations in
      soil samples ranged from ND to 2.79 ng/g for HCHs, ND to 2.83 ng/g for
      endosulfans, NDto 1.46 ng/g for heptachlor, ND to 2.12 ng/g for Aldrin and ND to
      1.81 ng/g for dieldrin. Spatial distribution of OCPs suggested prevalence of DDTs
      and HCHs at Guwahati and Itanagar, respectively. The close relationship between
      total organic carbon (TOC) and part of OCP compounds (especially alpha- and gamma
      HCH) indicated the important role of TOC in accumulation, binding and persistence
      of OCP in soil. Diagnostic ratio of DDT metabolites and HCH isomers showed DDT
      contamination is due to recent application of technical DDT and dicofol, and HCH
      contamination was due to mixture of technical HCH and lindane source. This was
      further confirmed by principal component analysis. Ecological risk analysis of
      OCP residues in soil samples concluded the moderate to severe contamination of
      soil.

PMID- 26300366
TI  - Intumescent flame retardant-derived P,N co-doped porous carbon as an efficient
      electrocatalyst for the oxygen reduction reaction.
AB  - An intumescent flame retardant (IFR), including melamine (MA), ammonium
      polyphosphate (APP), and polydopamine (PDA), was utilized as the precursor to
      prepare P,N co-doped hierarchically porous carbon which exhibited high
      electrocatalytic activity and durability for the oxygen reduction reaction (ORR).
      This finding indicates that an ingenious design of the precursor can lead to
      functional carbon materials using a simple process. 

PMID- 26300365
TI  - Diffusion chamber system for testing of collagen-based cell migration barriers
      for separation of ligament enthesis zones in tissue-engineered ACL constructs.
AB  - A temporary barrier separating scaffold zones seeded with different cell types
      prevents faster growing cells from overgrowing co-cultured cells within the same
      construct. This barrier should allow sufficient nutrient diffusion through the
      scaffold. The aim of this study was to test the effect of two variants of
      collagen-based barriers on macromolecule diffusion, viability, and the spreading
      efficiency of primary ligament cells on embroidered scaffolds. Two collagen
      barriers, a thread consisting of a twisted film tape and a sponge, were
      integrated into embroidered poly(lactic-co-caprolactone) and polypropylene
      scaffolds, which had the dimension of lapine anterior cruciate ligaments (ACL). A
      diffusion chamber system was designed and established to monitor nutrient
      diffusion using fluorescein isothiocyanate-labeled dextran of different molecular
      weights (20, 40, 150, 500 kDa). Vitality of primary lapine ACL cells was tested
      at days 7 and 14 after seeding using fluorescein diacetate and ethidium bromide
      staining. Cell spreading on the scaffold surface was measured using
      histomorphometry. Nuclei staining of the cross-sectioned scaffolds revealed the
      penetration of ligament cells through both barrier types. The diffusion chamber
      was suitable to characterize the diffusivity of dextran molecules through
      embroidered scaffolds with or without integrated collagen barriers. The diffusion
      coefficients were generally significantly lower in scaffolds with barriers
      compared to those without barriers. No significant differences between diffusion
      coefficients of both barrier types were detected. Both barriers were cyto
      compatible and prevented most of the ACL cells from crossing the barrier, whereby
      the collagen thread was easier to handle and allowed a higher rate of cell
      spreading. 

PMID- 26300364
TI  - Eco-friendly control of malaria and arbovirus vectors using the mosquitofish
      Gambusia affinis and ultra-low dosages of Mimusops elengi-synthesized silver
      nanoparticles: towards an integrative approach?
AB  - Mosquito-borne diseases represent a deadly threat for millions of people
      worldwide. However, the use of synthetic insecticides to control Culicidae may
      lead to high operational costs and adverse non-target effects. Plant-borne
      compounds have been proposed for rapid extracellular synthesis of mosquitocidal
      nanoparticles. Their impact against biological control agents of mosquito larval
      populations has been poorly studied. We synthesized silver nanoparticles (AgNP)
      using the aqueous leaf extract of Mimusops elengi as a reducing and stabilizing
      agent. The formation of AgNP was studied using different biophysical methods,
      including UV-vis spectrophotometry, TEM, XRD, EDX and FTIR. Low doses of AgNP
      showed larvicidal and pupicidal toxicity against the malaria vector Anopheles
      stephensi and the arbovirus vector Aedes albopictus. AgNP LC50 against A.
      stephensi ranged from 12.53 (I instar larvae) to 23.55 ppm (pupae); LC50 against
      A. albopictus ranged from 11.72 ppm (I) to 21.46 ppm (pupae). In the field, the
      application of M. elengi extract and AgNP (10 * LC50) led to 100 % larval
      reduction after 72 h. In adulticidal experiments, AgNP showed LC50 of 13.7 ppm
      for A. stephensi and 14.7 ppm for A. albopictus. The predation efficiency of
      Gambusia affinis against A. stephensi and A. albopictus III instar larvae was
      86.2 and 81.7 %, respectively. In AgNP-contaminated environments, predation was
      93.7 and 88.6 %, respectively. This research demonstrates that M. elengi
      synthesized AgNP may be employed at ultra-low doses to reduce larval populations
      of malaria and arbovirus vectors, without detrimental effects on predation rates
      of mosquito natural enemies, such as larvivorous fishes. 

PMID- 26300367
TI  - Secondhand Smoke Exposure Reduction Intervention in Chinese Households of Young
      Children: A Randomized Controlled Trial.
AB  - OBJECTIVE: To assess whether a theory-based, community health worker-delivered
      intervention for household smokers will lead to reduced secondhand smoke exposure
      to children in Chinese families. METHODS: Smoking parents or caregivers who had a
      child aged 5 years or younger at home were randomized to the intervention group
      (n = 164) to receive smoking hygiene intervention or to the comparison group (n =
      154). The intervention was delivered by trained community health workers.
      Outcomes were assessed at 2- and 6- month follow-up. RESULTS: Of the 318 families
      randomized, 98 (60%) of 164 intervention group and 82 (53%) of 154 of controls
      completed 6-month follow-up assessment. At the 6-month follow-up, 62% of
      intervention and 45% of comparison group households adopted complete smoking
      restrictions at home (P = .022); total exposure (mean number of cigarettes per
      week +/- standard deviation) from all smokers at home in the past 7 days was
      significantly lower among children in the intervention (3.29 +/- 9.06) than the
      comparison (7.41 +/- 14.63) group (P = .021); and mean urine cotinine level
      (ng/mL) was significantly lower in the intervention (0.030 +/- .065) than the
      comparison (0.087 +/- .027) group, P < .001). Participants rating of the overall
      usefulness of the intervention was 4.8 + 0.8 (1 standard deviation) on the 5
      point scale (1 not at all and 5 = very useful). CONCLUSIONS: The findings of this
      very first study in China showed that smoking hygiene intervention was effective
      in reducing children's exposure to secondhand smoke. These findings have
      implications for the development of primary health care-based secondhand smoke
      exposure reduction and family oriented smoking cessation interventions as China
      moves toward a smoke-free society.

PMID- 26300369
TI  - CFBSA: a novel and practical chlorinating reagent.
AB  - A structurally simple, highly reactive chlorinating reagent, N-chloro-N
      fluorobenzenesulfonylamine (CFBSA), was conveniently prepared from inexpensive
      Chloramine B in high yield. A wide range of substrates were chlorinated with it
      to obtain products in good to high yields and appropriate selectivity. 

PMID- 26300368
TI  - Validation of the Vaccination Confidence Scale: A Brief Measure to Identify
      Parents at Risk for Refusing Adolescent Vaccines.
AB  - OBJECTIVE: To validate a brief measure of vaccination confidence using a large,
      nationally representative sample of parents. METHODS: We analyzed weighted data
      from 9018 parents who completed the 2010 National Immunization Survey-Teen, an
      annual, population-based telephone survey. Parents reported on the immunization
      history of a 13- to 17-year-old child in their households for vaccines including
      tetanus, diphtheria, and acellular pertussis (Tdap), meningococcal, and human
      papillomavirus vaccines. For each vaccine, separate logistic regression models
      assessed associations between parents' mean scores on the 8-item Vaccination
      Confidence Scale and vaccine refusal, vaccine delay, and vaccination status. We
      repeated analyses for the scale's 4-item short form. RESULTS: One quarter of
      parents (24%) reported refusal of any vaccine, with refusal of specific vaccines
      ranging from 21% for human papillomavirus to 2% for Tdap. Using the full 8-item
      scale, vaccination confidence was negatively associated with measures of vaccine
      refusal and positively associated with measures of vaccination status. For
      example, refusal of any vaccine was more common among parents whose scale scores
      were medium (odds ratio, 2.08; 95% confidence interval, 1.75-2.47) or low (odds
      ratio, 4.61; 95% confidence interval, 3.51-6.05) versus high. For the 4-item
      short form, scores were also consistently associated with vaccine refusal and
      vaccination status. Vaccination confidence was inconsistently associated with
      vaccine delay. CONCLUSIONS: The Vaccination Confidence Scale shows promise as a
      tool for identifying parents at risk for refusing adolescent vaccines. The
      scale's short form appears to offer comparable performance.

PMID- 26300370
TI  - Development of a TaqMan assay for sensitive detection of all pestiviruses
      infecting cattle, including the emerging HoBi-like strains.
AB  - A real-time RT-PCR assay based on the TaqMan technology was developed for rapid
      and sensitive detection of pestiviruses infecting cattle, i.e., bovine viral
      diarrhea virus (BVDV) 1, BVDV-2, and the emerging HoBi-like pestiviruses. The
      assay was linear and reproducible, being able to detect as few as 10 copies of
      viral RNA. By real-time RT-PCR analysis of 986 biological samples collected from
      cattle herd with clinical signs suggestive of pestivirus infection and from
      animals recruited in a pestivirus surveillance programme, 165 pestivirus positive
      samples were detected, including 6 specimens, 2 nasal swabs, and 4 EDTA-blood
      samples, that tested negative by a gel-based RT-PCR assay targeting the 5'UTR.
      The developed TaqMan assay represents a new reliable and effective tool for rapid
      and sensitive diagnosis of infections caused by all pestiviruses circulating in
      cattle, thus being useful for extensive surveillance programs in geographic areas
      where HoBi-like pestiviruses are co-circulating with BVDV-1 and BVDV-2. 

PMID- 26300371
TI  - Genotyping of classical swine fever virus using high-resolution melt analysis.
AB  - Discrimination between different field and vaccine strains of classical swine
      fever virus (CSFV) is crucial for meaningful disease diagnosis and
      epidemiological investigation. In this study, a rapid method for differentiating
      vaccine strains and outbreak CSFV isolates by combined RT-PCR and high-resolution
      melt (HRM) analysis has been developed. The assay is based on PCR amplification
      of short fragments from the most variable region of CSFVgene E2, followed by HRM
      analysis of amplicons. Real-Time PCR/HRM for CSFV detection and differentiation
      analysis has sensitivity comparable to RT-qPCR and genotyping resolution
      comparable to E2 nucleotide sequencing. This assay in one step enables rapid and
      sensitive identification and genotype discrimination of CSFV in field samples,
      and thus will be valuable for CSF outbreak response and disease control. 

PMID- 26300372
TI  - An enzyme-linked immuno focus assay for rapid detection and enumeration, and a
      newborn mouse model for human non-polio enteroviruses associated with acute
      diarrhea.
AB  - We have recently reported significant association of non-polio enteroviruses
      (NPEVs) with acute and persistent diarrhea (18-21% of total diarrheal cases), and
      non-diarrheal Increased Frequency of Bowel Movements (IFoBM-ND) (about 29% of the
      NPEV infections) in children and that the NPEV-associated diarrhea was as
      significant as rotavirus diarrhea. However, their diarrhea-causing potential is
      yet to be demonstrated in an animal model system. Since the determination of
      virus titers by the traditional plaque assay takes 4-7 days, there is a need for
      development of a rapid method for virus titer determination to facilitate active
      clinical research on enterovirus-associated diarrhea. The goal of this study is
      to develop a cell-based rapid detection and enumeration method and to demonstrate
      the diarrhea-inducing potential of purified and characterized non-polio
      enteroviruses, which were isolated from diarrheic children. Here we describe
      generation of monoclonal and polyclonal antibodies against purified strains
      belonging to different serotypes, and development of an enzyme-linked immuno
      focus assay (ELIFA) for detection and enumeration of live NPEV particles in
      clinical and purified virus samples, and a newborn mouse model for NPEV diarrhea.
      Plaque-purified NPVEs, belonging to different serotypes, isolated from children
      with diarrhea, were grown in cell culture and purified by isopycnic CsCl density
      gradient centrifugation. By ELIFA, NPEVs could be detected and enumerated within
      12h post-infection. Our results demonstrated that Coxsackievirus B1 (CVB1) and
      CVB5 strains, isolated from diarrheic children, induced severe diarrhea in orally
      inoculated 9-12 day-old mouse pups, fulfilling Koch's postulates. The methods
      described here would facilitate studies on NPEV-associated gastrointestinal
      disease. 

PMID- 26300373
TI  - Vancouver type B2 and B3 periprosthetic fractures treated with revision total hip
      arthroplasty.
AB  - PURPOSE: Periprosthetic fractures are the fourth most common cause for hip
      revision and a devastating complication. Our purpose is to report results and
      quality of life following revision THA for Vancouver B2 and B3 fractures.
      METHODS: This was a retrospective review from January 2000 to November 2012 to
      identify all revision THA performed for Vancouver types B2 and B3 that had a
      minimum follow-up of two years. Routine post-operative and radiographic
      evaluation to assess patient survival, implant failure, complications and quality
      of life was involved. Statistical analysis was made with the Kaplan-Meier
      survival curve with 95 % confidence interval and the log rank (Mantel-Cox) test.
      RESULTS: A total of 76 fractures were included, with an average follow-up 74.4
      months. Mean age at the revision surgery was 75.7 years (range, 41-97 years; SD,
      12.4). Sixty-six cases were classified as Vancouver B2 and treated with distal
      fixation stem. Ten cases were Vancouver B3 and a proximal femoral allograft
      technique was used. The overall five-year Kaplan-Meier survival rate for the
      patients was 77.9 % (95 % CI, 67.4-88.4), and the ten-year rate was 65.1 % (95 %
      CI, 51.4-78.8). Five-year Kaplan-Meier survival rate for the implants was 89.6 %
      (95 % CI, 82.2-97); we presented seven failures. The mean SF-12 mental was 55.1
      (range, 31-68; SD, 8.1) and the physical was 37.4 (range, 16-55; SD, 9.4).
      CONCLUSION: Mortality rate after periprosthetic fractures is high as compared to
      other hip surgeries; our Kaplan-Meier analysis showed that it tends to plateau
      after five years. In our series the failure rate was low and occurred early in
      the post-operative period.

PMID- 26300374
TI  - Trauma related to falls from trees treated in a specialized trauma centre in
      Burkina-Faso-one hundred and six cases treated in one year.
AB  - PURPOSE: Falls from trees related traumas are rarely reported in literature. They
      are public health problems in developing countries where their frequency is still
      important. The aim of the study is to describe falls from trees related trauma
      patterns and to present preventative measures. METHODS: An annual ongoing
      prospective study was held in our trauma emergency department (ED) about all the
      patients who sustained an injury after a recent fall from tree. A questionnaire
      related to the patient and to the trauma was established. The data were encoded
      and analysed by a statistical software. RESULTS: One hundred six patients who
      sustained a fall from tree trauma, out of a total of 139, were studied. Most
      patients were under 15 years old (76.4 %); they were injured in fruits season (33
      %) after a fall from a fruit tree (mango trees, Shea trees, Nere, etc.) and were
      received late (86 %). Injuries were polymorphic from traumatic brain injuries
      (51.8 %) and spine injuries (13.2 %) to thoraco-abdominal (21.6 %) and limbs
      injuries (46.2 %). Three housewives were pregnant at the time of the trauma with
      secondary abortions. Patients were managed medically (33.9 %), surgically (19.8
      %) or by casting (34.9 %) with good outcome in 59 cases. Twelve patients refused
      medical care and two died. CONCLUSION: Education programs must focus on picking
      fruits and leaves in order to make them safe and prevent injuries related to
      these traditional or professional activities.

PMID- 26300375
TI  - Periprosthetic fractures of the distal femur following total knee arthroplasty:
      even very distal fractures can be successfully treated using internal fixation.
AB  - PURPOSE: We treat periprosthetic fracture of the distal femur above total knee
      arthroplasty using single or double plating and the minimally invasive plate
      osteosynthesis (MIPO) technique. Here, we report the results of using this
      operative treatment and our analysis of whether very distally extended fractures
      can also be successfully treated using internal fixation. METHODS: We
      retrospectively reviewed 32 periprosthetic distal femoral fractures. Mean patient
      age was 73 years and mean follow-up period 25 months. There were 11 (34.4 %) Su
      type I/II and 21 (65.6 %) type III fractures. All Su type I/II fractures were
      treated by single plating, whereas 14 of 21 (66.7 %) type III fractures were
      treated using double plating and the MIPO technique. We defined bony union as the
      primary endpoint of this study based on callus formation across the fracture site
      at two or more cortices (1 medial and 1 other) on 3D computed tomography (CT).
      RESULTS: Bony union was confirmed in 30 cases (93.8 %) after a mean time to union
      of 3.7 (range, 3-7) months. Two patients showed nonunion (6.2 %), and one
      demonstrated delayed union (3.1 %), none of whom complied with our rehabilitation
      protocol. There was one instance of nonunion among both Su types I/II and III
      fractures; however, this difference was not significant (p = 0.577). CONCLUSIONS:
      Periprosthetic fractures of the distal femur can be successfully healed using
      internal fixation, either the single- or double-plate MIPO technique, even for
      very distally extended fractures.

PMID- 26300376
TI  - Short-term regulation and alternative pathways of photosynthetic electron
      transport in Hibiscus rosa-sinensis leaves.
AB  - In this work, using the EPR and PAM-fluorometry methods, we have studied
      induction events of photosynthetic electron transport in Hibiscus rosa-sinensis
      leaves. The methods used are complementary, providing efficient tools for in situ
      monitoring of P700 redox transients and photochemical activity of photosystem II
      (PSII). The induction of P700(+) in dark-adapted leaves is characterized by the
      multiphase kinetics with a lag-phase, which duration elongates with the dark
      adaptation time. Analyzing effects of the uncoupler monensin and artificial
      electron carrier methylviologen (MV) on photooxidation of P700 and slow induction
      of chlorophyll a fluorescence (SIF), we could ascribe different phases of
      transient kinetics of electron transport processes in dark-adapted leaves to the
      following regulatory mechanisms: (i) acceleration of electron transfer on the
      acceptor side of PSI, (ii) pH-dependent modulation of the intersystem electron
      flow, and (iii) re-distribution of electron fluxes between alternative (linear,
      cyclic, and pseudocyclic) pathways. Monensin significantly decreases a level of
      P700(+) and inhibits SIF. MV, which mediates electron flow from PSI to O2 with
      consequent formation of H2O2, promotes a rapid photooxidation of P700 without any
      lag-phase peculiar to untreated leaves. MV-mediated water-water cycle (H2O->PSII
      >PSI->MV->O2->H2O2->H2O) is accompanied by generation of ascorbate free radicals.
      This suggests that the ascorbate peroxidase system of defense against reactive
      oxygen species is active in chloroplasts of H. rosa-sinensis leaves. In DCMU
      treated chloroplasts with inhibited PSII, the contribution of cyclic electron
      flow is insignificant as compared to linear electron flow. For analysis of
      induction events, we have simulated electron transport processes within the
      framework of our generalized mathematical model of oxygenic photosynthesis, which
      takes into account pH-dependent mechanisms of electron transport control and re
      distribution of electron fluxes between alternative pathways. The model
      adequately describes the main peculiarities of P700(+) induction and dynamics of
      the intersystem electron transport. 

PMID- 26300377
TI  - Input and uptake at 7 months predicts toddler vocabulary: the role of child
      directed speech and infant processing skills in language development.
AB  - Both the input directed to the child, and the child's ability to process that
      input, are likely to impact the child's language acquisition. We explore how
      these factors inter-relate by tracking the relationships among: (a) lexical
      properties of maternal child-directed speech to prelinguistic (7-month-old)
      infants (N = 121); (b) these infants' abilities to segment lexical targets from
      conversational child-directed utterances in an experimental paradigm; and (c) the
      children's vocabulary outcomes at age 2;0. Both repetitiveness in maternal input
      and the child's speech segmentation skills at age 0;7 predicted language outcomes
      at 2;0; moreover, while these factors were somewhat inter-related, they each had
      independent effects on toddler vocabulary skill, and there was no interaction
      between the two.

PMID- 26300378
TI  - Supportive interventions for enhancing dietary intake in malnourished or
      nutritionally at-risk adults: a systematic review of nonrandomised studies.
AB  - BACKGROUND: Supportive interventions for enhancing dietary intake in malnourished
      or nutritionally at risk adults are frequently recommended. A recent systematic
      review of randomised controlled trials identified limited and poor quality
      evidence to support their use. Observational studies have been shown to
      compliment and extend their evidence. This review aimed to synthesise evidence
      from nonrandomised studies aiming to improve nutritional intake in nutritionally
      vulnerable individuals and to describe their effects on cost, nutritional,
      clinical and patient centred outcomes. METHODS: Systematic searches of 10
      electronic databases were undertaken to May 2013. Reference lists of identified
      studies and systematic reviews were scrutinised and hand searching of relevant
      meeting abstracts was undertaken. Titles and abstracts were reviewed, data
      extracted by two research-ers working independently and summarised using a
      structured narrative format. RESULTS: Forty-one studies (n = 3751 participants)
      were identified for inclusion. Interventions identified included changes to the
      organisation of nutritional care (n = 15), changes to the feeding environment (n
      = 11), modification to meals (n = 6), supplementation of meals (n = 7) and
      recipients of home delivered meals (n = 2). Eighteen of 23 studies reported
      improvements in nutritional intake; however, effects on nutritional status,
      clinical outcomes and costs were reported in few studies and findings were
      inconsistent. Eighteen studies reported patient experience, highlighting benefits
      to nutritional status most commonly as judged by the carers but the methods used
      lacked rigour. CONCLUSIONS: This systematic review describes a range of
      interventions that may be implemented in clinical practice. A limited range of
      outcomes are reported and it is difficult to draw any meaningful conclusions on
      the effect of the different methods.

PMID- 26300380
TI  - Erratum.

PMID- 26300379
TI  - Complete mitochondrial genome and phylogenetic position of the Sicklefin weasel
      shark Hemigaleus microstoma.
AB  - The complete mitochondrial genome of the Sicklefin weasel shark Hemigaleus
      microstoma was first presented in this study. It was 16 701 bp in length with the
      typical gene arrangement in vertebrates. A total of 25 bp short intergenic spaces
      and 33 bp overlaps located in 12 and 9 gene junctions, respectively. The overall
      nucleotide composition was 31.0% A, 26.4% C, 13.5% G and 29.1% T. Two start (ATG
      and GTG) and three stop (TAG, AGG and TAA/T) codons were found in the protein
      coding genes. The size of 22 tRNA genes ranged from 67 to 75 bp. In the
      phylogenetic tree, H. microstoma (Hemigaleidae) was placed as sister to
      Galeocerdo cuvier (Carcharhinidae).

PMID- 26300381
TI  - Heterogeneity in Trajectories of Child Maltreatment Severity: A Two-Part Growth
      Mixture Model.
AB  - This study examined the trajectories of maltreatment severity and substantiation
      over a 24-month period among children (N = 82,396) with repeated maltreatment
      reports. Findings revealed 2 different longitudinal patterns. The first pattern,
      Elevated Severity, showed a higher level of maltreatment during the initial
      incident and increased maltreatment severity during subsequent incidents, but the
      substantiation rates for this class decreased over time. The second pattern,
      Lowered Severity, showed a much lower level of severity, but the likelihood of
      substantiation increased over time. The Elevated Severity class was composed of
      children with an elevated risk profile because of both individual and contextual
      risk factors including older age, female gender, caregivers' substance use
      problems, and a higher number of previous maltreatment reports. Implications of
      the findings are discussed. 

PMID- 26300382
TI  - Long-term quality of life outcomes and retreatment rates after robotic
      sacrocolpopexy.
AB  - OBJECTIVE: To evaluate the long-term outcomes and potential predictors of
      treatment failure after robotic sacrocolpopexy. METHODS: We identified 70
      consecutive patients from 2002 to 2012 with symptomatic post-hysterectomy vaginal
      vault prolapse that underwent robotic sacrocolpopexy. Multiple clinical and
      surgical variables were evaluated for potential association with treatment
      failure, which was defined as any repeat operation for recurrent prolapse or mesh
      related complications. RESULTS: The median age at surgery was 67 years
      (interquartile range 59-74 years) and median follow up was 72 months
      (interquartile range 39-114 months). Overall, six out of 70 patients (8.6%)
      underwent a total of six secondary surgeries, including four for recurrent
      prolapse (two anterior repairs, one posterior repair, one apical) and two mesh
      complications. No patient-related factors were associated with the risk of repeat
      surgery: age (P = 0.45), diabetes mellitus (P = 0.24), tobacco use (P = 0.61) or
      prior prolapse surgery (P = 0.1) on univariate analysis. Freedom from repeat
      prolapse surgery or surgery for mesh complication was 98% at 1 year, 95% at 3
      years and 90% at 6 years. At last follow up, 80% of patients reported that they
      would or probably would recommend robotic sacrocolpopexy to a family member or
      friend. CONCLUSIONS: Robotic sacrocolpopexy is associated with excellent long
      term outcomes. Recognition of long-term success is important for preoperative
      patient counseling.

PMID- 26300383
TI  - Age-related decrease in CD271(+) cells in human skin.
AB  - According to recent studies, stem cells are found in various tissues in our
      bodies. It has been reported that stem cells can reside in the skin tissues,
      including the epidermis, dermis, hair follicles and subcutaneous tissues.
      Homeostasis of the skin is maintained because these stem cells collaborate with
      each other to form new cells. We previously identified the CD271(p75NTR)(+) cell
      as a stem cell that was present in the epidermis, dermis and subcutaneous tissue,
      and further investigated the role of stem cells in wound healing and their
      association with skin disease. In this study, we investigated the localization of
      CD271(+) cells in human skin (epidermis and dermis) and its age-related changes
      in stem cells using CD271(+) cells. The study revealed that the number of
      CD271(+) cells in the epidermis and dermis decreased with aging. It is possible
      that such an age-related decrease in stem cells causes impaired regenerative
      ability and is associated with various skin diseases. If the relationship between
      stem cells and skin aging and diseases can be elucidated by investigations such
      as this study, it may lead to the development of novel anti-aging technologies
      and medical treatments for skin diseases in the future.

PMID- 26300384
TI  - Resection of a right atrial epithelioid hemangioendothelioma.
AB  - A right atrial mass excised from the heart of a 53-year-old man was incidentally
      found to be an epithelioid hemangioendothelioma (EHE). EHE is a rare malignant
      tumor with marked variability in clinical outcomes. Cardiac involvement is
      unusual but does occur [Bisesi MA, Broderick LS, Smith JA. MR demonstration of
      right atrial involvement in multifocal epithelioid hemangioendothelioma. AJR Am J
      Roentgenol 1996;167(4):953-4; Di Biasi P, Scrofani R, Santoli C. Cardiac
      hemangioendothelioma. Ann Thorac Surg 1995;59(3):792-3], and the prognostic is
      usually considered relatively good after resection. However, the tumor in this
      case shows atypical features, which raises concerns. In addition to complete en
      bloc resection, a close follow-up is considered mandatory. 

PMID- 26300386
TI  - On the role of the anterior prefrontal cortex in cognitive 'branching': An fMRI
      study.
AB  - The most anterior portion of prefrontal cortex (aPFC), more specifically Brodman
      Area 10 (BA10), has been implicated in 'branching operations', or the ability to
      perform tasks related to one goal, while keeping in working memory information
      related to a secondary goal. Such findings have been based on fMRI recordings
      under complex behavioral paradigms that compare 'branching' tasks with tasks
      where one goal is pursued at a time, but are limited by their complete reliance
      on verbal working memory and by small sample sizes. Here, we test the specificity
      of BA 10 to branching in similar behavioral paradigms but with a larger sample
      and in two different conditions involving verbal and visual working memory
      respectively. We find that BA 10 and other frontal and parietal brain areas are
      activated in all tasks, with an extent and level of significance increasing with
      the complexity of the task. We conclude that the activation of BA 10 is not
      specific to branching as previously hypothesized, but is related to the level of
      complexity of working memory performance. For further insight into the specific
      role of anterior portions of the frontal cortex we highlight the importance of
      simple control tasks with gradual and incremental increase in complexity. 

PMID- 26300385
TI  - What do pauses in narrative production reveal about the nature of word retrieval
      deficits in PPA?
AB  - Naming and word-retrieval deficits, which are common characteristics of primary
      progressive aphasia (PPA), differentially affect production across word classes
      (e.g., nouns, verbs) in some patients. Individuals with the agrammatic variant
      (PPA-G) often show greater difficulty producing verbs whereas those with the
      semantic variant (PPA-S) show greater noun deficits and those with logopenic PPA
      (PPA-L) evince no clear-cut differences in production of the two word classes. To
      determine the source of these production patterns, the present study examined
      word-finding pauses as conditioned by lexical variables (i.e., word class,
      frequency, length) in narrative speech samples of individuals with PPA-S (n=12),
      PPA-G (n=12), PPA-L (n=11), and cognitively healthy controls (n=12). We also
      examined the relation between pause distribution and cortical atrophy (i.e.,
      cortical thickness) in nine left hemisphere regions of interest (ROIs) linked to
      word production. Results showed higher overall pause rates for PPA compared to
      unimpaired controls; however, greater naming severity was not associated with
      increased pause rate. Across all groups, more pauses were produced before lower
      vs. higher frequency words, with no independent effects of word length after
      controlling for frequency. With regard to word class, the PPA-L group showed a
      higher rate of pauses prior to production of nouns compared to verbs, consistent
      with noun-retrieval deficits arising at the lemma level of word production. Those
      with PPA-G and PPA-S, like controls, produced similar pause rates across word
      classes; however, lexical simplification (i.e., production of higher-frequency
      and/or shorter words) was evident in the more-impaired word class: nouns for PPA
      S and verbs for PPA-G. These patterns are consistent with conceptual and/or lemma
      level impairments for PPA-S, predominantly affecting objects/nouns, and a lemma
      level verb-retrieval deficit for PPA-G, with a concomitant impairment in
      phonological encoding and articulation affecting overall pause rates. The greater
      tendency to pause before nouns was correlated with atrophy in the left precentral
      gyrus, inferior frontal gyrus and inferior parietal lobule, whereas the greater
      tendency to pause before less frequent and longer words was associated with
      atrophy in left precentral and inferior parietal regions. 

PMID- 26300387
TI  - Language and motor cortex response to comprehending accidental and intentional
      action sentences.
AB  - Understanding the meaning of others' actions involves mentally simulating those
      actions by oneself. Embodied theories of language espouse a prominent role for
      motor simulation in reading comprehension, especially when words, sentences, or
      narratives portray everyday actions. Inherent in these actions is the level of
      agency of the actor. Motor cortex activity in response to processing action verbs
      has been relatively well-established. What has been less explored, however, are:
      (1) the neural bases of determining whether an action is intentional or
      accidental (agency); and (2) whether agency influences level of motor simulation.
      This functional MRI study investigated how language and motor areas of the brain
      respond to sentences depicting intentional versus accidental action. 25 healthy
      adults read a series of sentences in the MRI scanner and determined whether the
      actions described were accidental or intentional. The main results include: (1)
      left hemisphere language areas (left inferior frontal gyrus, LIFG; left superior
      temporal gyrus, LSTG), premotor cortex (PM), and presupplementary motor area
      (pSMA) were strongly activated by both sentence types; (2) processing accidental
      action, relative to intentional action, elicited greater activity in LIFG, medial
      prefrontal cortex (MPFC), and left amygdala; no statistically significant
      activity was found in the opposite contrast; and (3) greater percent signal
      change was observed in LIFG while processing accidental action and in right
      precentral gyrus for intentional action. The results of this study support
      language and motor region involvement in action sentence comprehension in
      accordance with embodiment theories. Additionally, it provides new insight into
      the linguistic, integrative, and emotional demands of comprehending accidental
      action, its underlying neural circuitry, and its relationship to intentionality
      bias: the predisposition to ascribe purpose to action. 

PMID- 26300388
TI  - A retroactive spatial cue improved VSTM capacity in mild cognitive impairment and
      medial temporal lobe amnesia but not in healthy older adults.
AB  - Visual short-term memory (VSTM) is a vital cognitive ability, connecting visual
      input with conscious awareness. VSTM performance declines with mild cognitive
      impairment (MCI) and medial temporal lobe (MTL) amnesia. Many studies have shown
      that providing a spatial retrospective cue ("retrocue") improves VSTM capacity
      estimates for healthy young adults. However, one study has demonstrated that
      older adults are unable to use a retrocue to inhibit irrelevant items from
      memory. It is unknown whether patients with MCI and MTL amnesia will be able to
      use a retrocue to benefit their memory. We administered a retrocue and a baseline
      (simultaneous cue, "simucue") task to young adults, older adults, MCI patients,
      and MTL cases. Consistent with previous findings, young adults showed a retrocue
      benefit, whereas healthy older adults did not. In contrast, both MCI patients and
      MTL cases showed a retrocue benefit--the use of a retrocue brought patient
      performance up to the level of age-matched controls. We speculate that the
      patients were able to use the spatial information from the retrocue to reduce
      interference and facilitate binding items to their locations.

PMID- 26300389
TI  - Mental health correlates of drug treatment among women who use methamphetamine.
AB  - BACKGROUND AND OBJECTIVES: Women comprise over one-third of people who use
      methamphetamine in the United States and have a higher prevalence of negative
      mental health consequences of methamphetamine use than men. Yet, few studies have
      investigated the mental health correlates of drug treatment among this
      population. We examined the relationship between mental disorders, mental health
      treatment, and drug treatment among women who use methamphetamine. METHODS: We
      used respondent-driven sampling to recruit women who use methamphetamine (N =
      322) for a survey about mental disorders, mental health treatment, drug use and
      treatment, and sociodemographic factors. Bivariate and multivariable logistic
      regression analyses were conducted. RESULTS: Bivariate analyses indicated that
      race/ethnicity, mental health treatment, and presence and number of mental
      disorders were associated with drug treatment. Multivariable analyses revealed
      that women who reported mental health treatment during a 6-month period had
      almost twice the odds of also reporting drug treatment than other women (AOR =
      1.90; 95% CI = 1.11, 3.25), after controlling for mental disorders and
      race/ethnicity. CONCLUSION: Among women who use methamphetamine, participation in
      one service system (mental health treatment) is a key factor in increasing the
      odds of participation in another service system (drug treatment). Further
      research should establish the temporal association between mental health and drug
      treatment. SCIENTIFIC SIGNIFICANCE: The present study demonstrates the
      association between mental health treatment and drug treatment, above and beyond
      presence or number of mental disorders, and provides direction for drug treatment
      providers seeking to improve treatment entry and participation among women who
      use methamphetamine.

PMID- 26300390
TI  - Social, spatial, and temporal organization in a complex insect society.
AB  - High-density living is often associated with high disease risk due to density
      dependent epidemic spread. Despite being paragons of high-density living, the
      social insects have largely decoupled the association with density-dependent
      epidemics. It is hypothesized that this is accomplished through prophylactic and
      inducible defenses termed 'collective immunity'. Here we characterise segregation
      of carpenter ants that would be most likely to encounter infectious agents (i.e.
      foragers) using integrated social, spatial, and temporal analyses. Importantly,
      we do this in the absence of disease to establish baseline colony organization.
      Behavioural and social network analyses show that active foragers engage in more
      trophallaxis interactions than their nest worker and queen counterparts and
      occupy greater area within the nest. When the temporal ordering of social
      interactions is taken into account, active foragers and inactive foragers are not
      observed to interact with the queen in ways that could lead to the meaningful
      transfer of disease. Furthermore, theoretical resource spread analyses show that
      such temporal segregation does not appear to impact the colony-wide flow of food.
      This study provides an understanding of a complex society's organization in the
      absence of disease that will serve as a null model for future studies in which
      disease is explicitly introduced. 

PMID- 26300391
TI  - Differences in gene expression and alterations in cell cycle of acute myeloid
      leukemia cell lines after treatment with JAK inhibitors.
AB  - Janus kinase (JAK) inhibitors are a promising treatment strategy in several
      hematological malignancies and autoimmune diseases. A number of inhibitors are in
      clinical development, and two have already reached the market. Unfortunately, all
      of them are burdened with different toxicity profiles. To check if the JAK
      inhibitors of different selectivity evoke different responses on JAK2-dependent
      and independent cells, we have used three acute myeloid leukemia cell lines with
      confirmed JAK2 mutation status. We have found that JAK inhibitors exert distinct
      effect on the expression of BCLXL, CCND1 and c-MYC genes, regulated by JAK
      pathway, in JAK2 wild type cells in comparison to JAK2 V617F-positive cell lines.
      Moreover, cell cycle analysis showed that inhibitors alter the cycle by arresting
      cells in different phases. Our results suggest that observed effect of JAK2
      inhibitors on transcription and cell cycle level in different cell lines are
      associated not with activity within JAK family, but presumably with other off
      target activities. 

PMID- 26300392
TI  - alpha2-Adrenergic modulation of the glutamate receptor and transporter function
      in a chronic ocular hypertension model.
AB  - Excitotoxicity, glutamate-induced toxic effects to retinal ganglion cells (RGCs),
      is one of several mechanisms of RGC loss suggested in glaucoma. In this study, we
      focused on the role of glutamate transporter of glial cells as well as N-methyl-d
      aspartate (NMDA) receptor with regard to glutamate toxicity in glaucoma. We also
      investigated whether alpha2-adrenoceptor activation could modulate glutamate
      transporters and NMDA receptors in a chronic ocular hypertension model.
      Brimonidine 0.15% was administered topically to the eyes of experimental glaucoma
      and control animals twice daily. After 8 weeks of intraocular pressure (IOP)
      elevation, staining with terminal deoxynucleotidyl transferase-mediated dUTP nick
      end labeling (TUNEL) revealed an increase in the ganglion cell layer, and the
      number of TUNEL-positive cells was reduced by brimonidine treatment (P<0.05).
      Animals with experimentally induced glaucoma exhibited an increase in retinal
      stress marker glial fibrillary acidic protein (GFAP) immunoreactivity;
      brimonidine treatment reduced GFAP. Excitatory amino acid transporter 1(EAAT1)
      expression remained stable throughout the period of chronic ocular hypertension.
      alpha2-Adrenergic treatment upregulated EAAT1 protein levels (P<0.05). NMDA
      receptor (GluN1) expression was stimulated by chronic elevation of IOP, and GluN1
      positive cells in ganglion cell layer were co-localized with TUNEL staining.
      Brimonidine administration suppressed GluN1 levels (P<0.05). These results
      indicate that brimonidine decreased RGC apoptosis, upregulating EAAT1 and
      downregulating NMDA receptors. We suggest that topical brimonidine treatment may
      decrease the glutamate excitotoxicity through modulation of glutamate transporter
      and NMDA receptor in glaucoma. 

PMID- 26300393
TI  - Genetic variations of hOCT1 gene and CYP3A4/A5 genes and their association with
      imatinib response in Chronic Myeloid Leukemia.
AB  - There is an increasing body of evidence demonstrating that mechanisms independent
      of BCR/ABL gene also contribute to imatinib resistance in Chronic Myeloid
      Leukemia (CML). It has been extensively reported that polymorphisms of the genes
      associated with imatinib metabolization and imatinib influx/efflux play an
      important role in the disease resistance. We investigated the impact of 12
      genetic variants of the two genes, CYP3A4/A5 and the human cation transporter 1
      gene (hOCT1) on the clinical outcome, in a cohort of 106 newly diagnosed CML
      patients. In the patient cohort investigated, only 6 variant alleles could be
      detected. The others were not present and could not be investigated. Two
      polymorphisms, CYP3A5*3 (rs776746)and hOCT1 M408V (rs628031), were significantly
      associated with the Complete Cytogenetic Response (CCyR) at 6 months and Major
      Molecular Response (MMR) at 12 months. The presence of favourable alleles at
      M408V and M420del in combination was associated with a MMR at 12 months.
      Functional polymorphisms of the genes associated with imatinib influx and
      metabolization may play a role in predicting primary response to imatinib and
      treatment outcome. 

PMID- 26300394
TI  - Treatment with curcumin alleviates sublesional bone loss following spinal cord
      injury in rats.
AB  - This work aimed to investigate the therapeutic effect of curcumin on sublesional
      bone loss induced by spinal cord injury (SCI) in rats. SCI model in this work was
      generated in rats by surgical transaction of the cord at the T10-12 level. After
      the surgery, animals were treated with curcumin (110 mg/kg body mass/day, via
      oral gavages) for 2 weeks. Treatment of SCI rats with curcumin prevented the
      reduction of bone mass in tibiae and femurs, preserved bone microstructure
      including trabecular bone volume fraction, trabecular number, and trabecular
      thickness in proximal tibiae, and preserved mechanical properties of femoral
      midshaft. Treatment of SCI rats with curcumin increased osteoblast surface and
      reduced osteoclast surface in proximal tibiae. Treatment of SCI rats with
      curcumin increased osteocalcin mRNA expression and reduced mRNA levels of
      tartrate-resistant acid phosphatase and mRNA ratio of receptor activator of NF
      kappaB ligand/osteoprotegerin in distal femurs. Treatment of SCI rats with
      curcumin reduced serum and femoral levels of thiobarbituric acid reactive
      substances. Treatment of SCI rats with curcumin had no significant effect on
      serum 25(OH)D, but enhanced mRNA and protein expression of vitamin D receptor
      (VDR) in distal femurs. Treatment of SCI rats with curcumin enhanced mRNA levels
      of Wnt3a, Lrp5, and ctnnb1 and upregulated protein expression of beta-catenin in
      distal femurs. In conclusions, treatment with curcumin abated oxidative stress,
      activated VDR, and enhanced Wnt/beta-catenin pathway, which might explain its
      beneficial effect against sublesional bone loss following SCI in rats, at least
      in part.

PMID- 26300395
TI  - Effects of exercise training together with tamoxifen in reducing mammary tumor
      burden in mice: Possible underlying pathway of miR-21.
AB  - Exercise training has an anti-tumor effect and can reduce tumor growth; however,
      the exact underlying mechanisms of its protective effects are still obscure.
      MicroRNA (miR)-21 is a predictor in cancer survival, and has a potential use as
      an indicator of therapeutic outcome in breast malignancies. Forty-eight female
      BALB/c mice were equally divided into six groups to investigate the effects of
      interval exercise training with tamoxifen on miR-21 expression and its possible
      assumed mechanisms in an estrogen receptor-positive breast cancer model. ELISA,
      immunohistochemistry, western blot, qRT-PCR assays were performed at the end of
      the study. Tumor size was significantly declined in exercise training and
      tamoxifen groups compared to tumor group (P<0.05). Expression of miR-21 was
      significantly down-regulated in trained and tamoxifen treated mice in comparison
      with tumor group (P<0.05). Exercise training was as effective as tamoxifen
      treatment in decreasing serum estradiol and ER-alpha expression (P<0.05).
      Exercise training and tamoxifen reduced tumor IL-6 levels, NF-kB and STAT3
      expressions, and up-regulated TPM1 and PDCD4 expressions (P<0.05). Both exercise
      and tamoxifen had synergistic effects in reducing miR-21 and Bcl-2, and up
      regulating PDCD4 expression. Results showed that interval exercise training may
      reduce mammary tumor burden in mice through possible underlying pathway of miR
      21. 

PMID- 26300396
TI  - Fibrinogen-derived fibrinostatin inhibits tumor growth through anti-angiogenesis.
AB  - Angiogenesis is a prerequisite of tumor growth and metastasis and, thus, anti
      angiogenesis treatment has become an important part of cancer therapy. A 15-amino
      acid peptide of the fibrinogen alpha chain, fibrinostatin, was previously found
      in serum samples of gastric cancer patients. Herein we demonstrated that
      fibrinostatin has anti-angiogenesis activity in several angiogenesis models and
      it reduces tumor growth in mouse xenografts and allografts. Increased tumor
      necrosis and reduced microvessel density in tumors were observed in mouse
      xenograft models. Fibrinostatin inhibited proliferation and induced apoptosis in
      HUVEC, but not in cancer cells. In addition, fibrinostatin specifically entered
      HUVEC. Fibrinostatin also prevented migration, adhesion and tubule formation of
      HUVEC in vitro. A single-dose acute toxicity testing and a repeated-dose chronic
      toxicity study in the mouse, rat and monkey indicated that fibrinostatin had a
      wide margin of safety. Taken together, fibrinostatin shows promise as a potential
      anti-angiogenesis therapeutic agent. 

PMID- 26300398
TI  - Neuroprotection by safinamide in the 6-hydroxydopamine model of Parkinson's
      disease.
AB  - AIMS: Current therapies in Parkinson's disease mainly treat symptoms rather than
      provide effective neuroprotection. We examined the effects of safinamide
      (monoamine oxidase B and sodium channel blocker) on microglial activation and the
      degeneration of dopaminergic neurons in a rat model of PD in vivo, and on
      microglia in vitro. METHODS: Rats received unilateral stereotaxic injection of 6
      hydroxydopamine into the medial forebrain bundle on day 0: The contralateral side
      served as control. Safinamide or vehicle was delivered from days 0 or 1, for 7
      days, via sub-cutaneous mini-pumps. RESULTS: In vehicle-treated rats 6
      hydroxydopamine caused a significant increase in the number of activated MHC
      II(+) microglia compared with the contralateral side, and only 50% of the
      dopaminergic neurons survived in the ipsilateral SNc. In contrast, rats treated
      daily with safinamide 50 and 150 mg/ml (on day 0 or 1) exhibited a significantly
      reduced number of activated microglia (55% reduction at 150 mg/ml) and a
      significant protection of dopaminergic neurons (80% of neurons survived) (P <
      0.001) compared with vehicle-treated controls. Rasagiline, a monoamine oxidase B
      inhibitor, and lamotrigine, a sodium channel blocking drug, also protected
      dopaminergic neurons, indicating that safinamide may act by either or both
      mechanisms. Safinamide also reduced the activation of microglial cells in
      response to lipopolysaccharide exposure in vitro. CONCLUSION: Safinamide therapy
      suppresses microglial activation and protects dopaminergic neurons from
      degeneration in the 6-hydroxydopamine model of PD, suggesting that the drug not
      only treats symptoms but also provides neuroprotection.

PMID- 26300397
TI  - Rhomboid domain containing 1 promotes colorectal cancer growth through activation
      of the EGFR signalling pathway.
AB  - Rhomboid proteins perform a wide range of important functions in a variety of
      organisms. Recent studies have revealed that rhomboid proteins are involved in
      human cancer progression; however, the underlying molecular mechanism remains
      largely unclear. Here we show that RHBDD1, a rhomboid intramembrane serine
      protease, is highly expressed and closely associated with survival in patients
      with colorectal cancer. We observe that inactivation of RHBDD1 decreases tumor
      cell growth. Further studies show that RHBDD1 interacts with proTGFalpha and
      induces the ADAM-independent cleavage and secretion of proTGFalpha. The secreted
      TGFalpha further triggers the activation of the EGFR/Raf/MEK/ERK signalling
      pathway. Finally, the positive correlation of RHBDD1 expression with the
      EGFR/Raf/MEK/ERK signalling pathway is further corroborated in a murine model of
      colitis-associated colorectal cancer. These findings provide evidence of a growth
      promoting role for RHBDD1 in colorectal cancer and may aid the development of
      tumor biomarkers or antitumor therapeutics. 

PMID- 26300399
TI  - Neurotoxicological and thyroid evaluations of rats developmentally exposed to
      tris(1,3-dichloro-2-propyl)phosphate (TDCIPP) and tris(2-chloro-2-ethyl)phosphate
      (TCEP).
AB  - Tris(1,3-dichloro-2-propyl)phosphate (TDCIPP) and tris(2-chloro-2-ethyl)phosphate
      (TCEP) are organophosphorous flame retardants with widespread usage and human
      exposures through food, inhalation, and dust ingestion. They have been detected
      in human tissues including urine and breast milk. Reports of disrupted neural
      growth in vitro, abnormal development in larval zebrafish, and altered thyroid
      hormones in several species have raised concern for neurodevelopmental toxicity.
      This is especially the case for TDCIPP, which is more potent and has more
      activity in those assays than does TCEP. We evaluated the potential for
      developmental neurotoxicity of TDCIPP and TCEP in a mammalian model. Pregnant
      Long-Evans rats were administered TDCIPP (15, 50, or 150 mg/kg/day) or TCEP (12,
      40, 90 mg/kg/day) via oral gavage from gestational day 10 to weaning. Corn oil
      was the vehicle control in both studies. Body weight and righting reflex
      development were monitored in all pups. A subset of offspring at culling and
      weaning, and dams at weaning, were sacrificed for serum and organ collection for
      measurement of brain, liver, and thyroid weights, serum thyroid levels, and serum
      and brain acetylcholinesterase activities. Brain weights were also measured in a
      group of adult TDCIPP-treated offspring. One male and one female from each litter
      were allocated for behavioral testing at several ages: standard locomotor
      activity (preweaning, postweaning, adults), locomotor activity including a
      lighting change mid-way (postweaning, adults), elevated zero maze (postweaning,
      adults), functional observational battery (FOB; postweaning, adults), and Morris
      water maze (place learning, reference and working memory; adults). Neither
      chemical produced changes in maternal body weight or serum thyroid hormones, but
      relative liver weight was increased at the high doses of both TDCIPP and TCEP. In
      offspring, there were no effects on viability, litter size, or birth weight. With
      TDCIPP, absolute liver weights were lower at weaning and weight gain was lower in
      the high-dose offspring until about two months of age. Thyroid hormones and brain
      weights were not altered and acetylcholinesterase (both brain and serum) was not
      inhibited by either chemical. TDCIPP-treated offspring showed slight differences
      in floating in the water maze, hindlimb grip strength, and altered activity
      habituation, whereas TCEP-treated rats showed differences in quadrant time
      (probe) and middle-zone preference in the water maze. Regarding these few
      changes, the effects were minimal, mostly not related to dose, and did not appear
      treatment-related or biologically significant. Overall, these data do not support
      the potential for thyrotoxicity or developmental neurotoxicity produced by TDCIPP
      or TCEP.

PMID- 26300400
TI  - Tribology studies of the natural knee using an animal model in a new whole joint
      natural knee simulator.
AB  - The successful development of early-stage cartilage and meniscus repair
      interventions in the knee requires biomechanical and biotribological
      understanding of the design of the therapeutic interventions and their
      tribological function in the natural joint. The aim of this study was to develop
      and validate a porcine knee model using a whole joint knee simulator for
      investigation of the tribological function and biomechanical properties of the
      natural knee, which could then be used to pre-clinically assess the tribological
      performance of cartilage and meniscal repair interventions prior to in vivo
      studies. The tribological performance of standard artificial bearings in terms of
      anterior-posterior (A/P) shear force was determined in a newly developed six
      degrees of freedom tribological joint simulator. The porcine knee model was then
      developed and the tribological properties in terms of shear force measurements
      were determined for the first time for three levels of biomechanical constraints
      including A/P constrained, spring force semi-constrained and A/P unconstrained
      conditions. The shear force measurements showed higher values under the A/P
      constrained condition (predominantly sliding motion) compared to the A/P
      unconstrained condition (predominantly rolling motion). This indicated that the
      shear force simulation model was able to differentiate between tribological
      behaviours when the femoral and tibial bearing was constrained to slide or/and
      roll. Therefore, this porcine knee model showed the potential capability to
      investigate the effect of knee structural, biomechanical and kinematic changes,
      as well as different cartilage substitution therapies on the tribological
      function of natural knee joints. 

PMID- 26300402
TI  - Low-density lipoprotein accumulation within a carotid artery with multilayer
      elastic porous wall: fluid-structure interaction and non-Newtonian
      considerations.
AB  - Low-density lipoprotein (LDL), which is recognized as bad cholesterol, typically
      has been regarded as a main cause of atherosclerosis. LDL infiltration across
      arterial wall and subsequent formation of Ox-LDL could lead to atherogenesis. In
      the present study, combined effects of non-Newtonian fluid behavior and fluid
      structure interaction (FSI) on LDL mass transfer inside an artery and through its
      multilayer arterial wall are examined numerically. Navier-Stokes equations for
      the blood flow inside the lumen and modified Darcy's model for the power-law
      fluid through the porous arterial wall are coupled with the equations of mass
      transfer to describe LDL distributions in various segments of the artery. In
      addition, the arterial wall is considered as a heterogeneous permeable elastic
      medium. Thus, elastodynamics equation is invoked to examine effects of different
      wall elasticity on LDL distribution in the artery. Findings suggest that non
      Newtonian behavior of filtrated plasma within the wall enhances LDL accumulation
      meaningfully. Moreover, results demonstrate that at high blood pressure and due
      to the wall elasticity, endothelium pores expand, which cause significant
      variations on endothelium physiological properties in a way that lead to higher
      LDL accumulation. Additionally, results describe that under hypertension, by
      increasing angular strain, endothelial junctions especially at leaky sites expand
      more dramatic for the high elastic model, which in turn causes higher LDL
      accumulation across the intima layer and elevates atherogenesis risk. 

PMID- 26300401
TI  - Feasible muscle activation ranges based on inverse dynamics analyses of human
      walking.
AB  - Although it is possible to produce the same movement using an infinite number of
      different muscle activation patterns owing to musculoskeletal redundancy, the
      degree to which observed variations in muscle activity can deviate from optimal
      solutions computed from biomechanical models is not known. Here, we examined the
      range of biomechanically permitted activation levels in individual muscles during
      human walking using a detailed musculoskeletal model and experimentally-measured
      kinetics and kinematics. Feasible muscle activation ranges define the minimum and
      maximum possible level of each muscle's activation that satisfy inverse dynamics
      joint torques assuming that all other muscles can vary their activation as
      needed. During walking, 73% of the muscles had feasible muscle activation ranges
      that were greater than 95% of the total muscle activation range over more than
      95% of the gait cycle, indicating that, individually, most muscles could be fully
      active or fully inactive while still satisfying inverse dynamics joint torques.
      Moreover, the shapes of the feasible muscle activation ranges did not resemble
      previously-reported muscle activation patterns nor optimal solutions, i.e. static
      optimization and computed muscle control, that are based on the same
      biomechanical constraints. Our results demonstrate that joint torque requirements
      from standard inverse dynamics calculations are insufficient to define the
      activation of individual muscles during walking in healthy individuals.
      Identifying feasible muscle activation ranges may be an effective way to evaluate
      the impact of additional biomechanical and/or neural constraints on possible
      versus actual muscle activity in both normal and impaired movements. 

PMID- 26300403
TI  - Joint kinematics from functional adaptation: A validation on the tibio-talar
      articulation.
AB  - Biologic tissues respond to the biomechanical conditions to which they are
      exposed by modifying their architecture. Experimental evidence from the
      literature suggests that the aim of this process is the mechanical optimization
      of the tissues (functional adaptation). In particular, this process must produce
      articular surfaces that, in physiological working conditions, optimize the
      contact load distribution or, equivalently, maximize the joint congruence. It is
      thus possible to identify the space of adapted joint configurations (or adapted
      space of motion) starting solely from knowledge of the shape of the articular
      surfaces, by determining the envelope of the maximum congruence configurations.
      The aim of this work was to validate this hypothesis by testing its application
      on 10 human ankle joints. Digitalizations of articular surfaces were acquired in
      10 in-vitro experimental sessions, together with the natural passive tibio-talar
      motion, which may be considered as representative of the adapted space of motion.
      This latter was predicted numerically by optimizing the joint congruence. The
      highest mean absolute errors between each component of predicted and experimental
      motion were 2.07 degrees  and 2.29 mm respectively for the three rotations and
      translations. The present kinematic model replicated the experimentally observed
      motion well, providing a reliable subject-specific representation of the joint
      motion starting solely from articulating surface shapes.

PMID- 26300405
TI  - The rise or fall of the nanny state?

PMID- 26300404
TI  - Stochastic predictors from the DXA scans of human lumbar vertebrae are correlated
      with the microarchitecture parameters of trabecular bone.
AB  - The purpose of this study was to provide a novel stochastic assessment of
      inhomogeneous distribution of bone mineral density (BMD) from the Dual-energy X
      ray Absorptiometry (DXA) scans of human lumbar vertebrae and identify the
      stochastic predictors that were correlated with the microarchitecture parameters
      of trabecular bone. Eighteen human lumbar vertebrae with intact posterior
      elements from 5 cadaveric spines were scanned in the posterior-anterior
      projection using a Hologic densitometer. The BMD map of human vertebrae was
      obtained from the raw data of DXA scans by directly operating on the transmission
      measurements of low- and high-energy X-ray beams. Stochastic predictors were
      calculated by fitting theoretical models onto the experimental variogram of the
      BMD map, rather than grayscale images, from DXA scans. In addition,
      microarchitecture parameters of trabecular bone were measured from the 3D images
      of human vertebrae acquired using a Micro-CT scanner. Significant correlations
      were observed between stochastic predictors and microarchitecture parameters. The
      sill variance, representing the standard deviation of the BMD map to some extent,
      had significantly positive correlations with bone volume, trabecular thickness,
      trabecular number and connectivity density. The sill variance was also negatively
      associated with bone surface to volume ratio and trabecular separation. This
      study demonstrates that the stochastic assessment of the inhomogeneous
      distribution of BMD from DXA scans of human lumbar vertebrae can reveal
      microarchitecture information of trabecular bone. However, future studies are
      needed to examine the potential of stochastic predictors from routine clinical
      DXA scans in providing bone fragility information complementary to BMD. 

PMID- 26300406
TI  - Preparation and evaluation of a sustained-release buckwheat noodle.
AB  - BACKGROUND: Different carbohydrates elicit various effects on the digestibility
      and the glucose release rate, so it is of interest to develop a sustained-release
      noodle based on the combination of different carbohydrates and reveal the
      sustained-release mechanism. RESULTS: The data obtained suggest that xanthan and
      konjac gum exhibited excellent and synergistic sustained-release properties,
      whereas cornstarch showed the lowest average digestion rate. The sustained
      release was particularly evident when the noodle consisted of the following
      components: 50 g of 25 g kg(-1) hydrophilic colloid mixture solution composed of
      a 1:1 mass ratio of xanthan:konjac gum and 100 g of reconstructed flour
      consisting of 200 g kg(-1) buckwheat flour, 400 g kg(-1) cornstarch, and 400 g
      kg(-1) plain flour. The morphological structure of noodles revealed that the
      composite hydrophilic colloids strengthened the interaction between the gluten
      network and starch granules. This buried starch within the three-dimensional
      structure thereby releasing glucose in a slow and sustained way. The most
      suitable model to describe glucose release from noodles was the Ritger-Peppas
      equation, which revealed that matrix erosion contributed to the release
      mechanism. CONCLUSION: These findings indicate that the controlled use of
      hydrophilic colloids and starches in manufacturing noodles could modulate the
      glucose sustained-release. (c) 2015 Society of Chemical Industry.

PMID- 26300408
TI  - Conservative or radical surgery for pediatric papillary thyroid carcinoma: A
      systematic review of the literature.
AB  - BACKGROUND: Pediatric papillary thyroid carcinoma (PTC) is characterized by an
      aggressive clinical course. Early diagnosis is a challenge and treatment consists
      principally of partial or total thyroidectomy+/-neck dissection and radioactive
      iodine therapy. Due to the rarity of PTC in children, there is no consensus on
      optimal surgical treatment. METHODS AND RESULTS: A literature search was carried
      out using PubMed, Embase, Medline, Cochrane and Web of Science. Seven studies
      (489 patients) investigating the outcome of surgically managed pediatric PTC were
      identified. No clear advantage in survival or recurrence rate was found for total
      thyroidectomy compared to other surgical approaches. CONCLUSION: Despite the
      aggressive behavior of PTC, prognosis is good, with low mortality. After removal
      of disease and prevention of recurrence, reduction of iatrogenic complications
      are a priority in this age group. Due to the paucity of available evidence, this
      review cannot recommend conservative or radical surgery for pediatric papillary
      thyroid carcinoma. To answer this question, we recommend the establishment of a
      randomized controlled trial with adequately matched baseline variables.

PMID- 26300409
TI  - Response to Letter to the Editor for "Tonsillectomy versus Tonsillotomy: A study
      of parental preference".

PMID- 26300407
TI  - Endosialin-expressing bone sarcoma stem-like cells are highly tumor-initiating
      and invasive.
AB  - It has been reported that the presence of a small group of cancer stem-like 'side
      population (SP)' cells is responsible for therapy failure and tumor recurrence.
      The present study demonstrated that primary human osteosarcoma samples contained
      a SP of about 3.9% which overexpressed ABC transporters, including ABCA1, ABCB1,
      ABCB2 and ABCG2, which are associated with drug resistance and may have
      contributed to multi-drug resistance of SP cells. Furthermore, these SP cells
      displayed increased expression of endosialin (CD248) and other stem cell surface
      proteins, including CD133, octamer-binding transcription factor 3/4A, Nanog and
      Nestin, which are ultimately responsible for high self-renewal and deregulated
      cell proliferation. In addition, it was shown that endosialin-overexpressing SP
      cells were able to regenerate the tumor population and had a high invasive
      potential. Therefore, the present study suggested that osteosarcoma SP cells were
      cancer stem cells, as they displayed stem-like properties; furthermore,
      endosialin may be a potential target to prevent osteosarcoma recurrence following
      chemotherapy.

PMID- 26300410
TI  - Preparation of a permethylated beta-cyclodextrin chiral stationary phase by one
      pot hydrosilylation and immobilization at the C2 position for chiral high
      performance liquid chromatography.
AB  - A novel cyclodextrin intermediate, mono-2(A)-allylcarbamido-2(A)-deoxy
      permethylated beta-cyclodextrin, was synthesized by reacting allylamine and newly
      prepared mono-2(A)-azido-2(A)-deoxy-permethylated beta-cyclodextrin by the
      Staudinger reaction and anchored onto porous silica beads by a one-pot
      hydrosilylation and immobilization procedure to afford a novel chiral stationary
      phase. This stationary phase acts as a new member of the previous chiral
      stationary phase series immobilized on the cyclodextrin C2 position. This
      stationary phase depicted enantiomeric separation abilities toward a series of
      bicyclic and tricyclic racemates under reversed-phase conditions. The resolutions
      for hesperetin and naringenin achieved on the current phase reached 3.91 and
      1.11, respectively, much higher than the previous permethylated beta-cyclodextrin
      with the linkage at the C6 position.

PMID- 26300411
TI  - Measuring subcutaneous temperature and differential rates of rewarming from
      hibernation and daily torpor in two species of bats.
AB  - Prolonged and remote measurement of body temperature (Tb) in undisturbed small
      hibernators was not possible in the past because of technological limitations.
      Although passive integrated transponders (PITs) have been used previously to
      measure subcutaneous temperature (Tsub) during daily torpor in a small marsupial,
      no study has attempted to use these devices at Tbs below 10 degrees C. Therefore,
      we investigated whether subcutaneous interscapular PITs can be used as a viable
      tool for measuring Tb in a small hibernating bat (Nyctophilus gouldi; Ng) and
      compared it with measurements of Tb during daily torpor in a heterothermic bat
      (Syconycteris australis; Sa). The precision of transponders was investigated as a
      function of ambient temperature (Ta) and remote Tsub readings enabled us to
      quantify Tsub-Tb differentials during steady-state torpor and arousal.
      Transponders functioned well outside the manufacturer's recommended range, down
      to ~5 degrees C. At rest, Tsub and rectal Tb (Trec) were strongly correlated for
      both bat species (Ng r(2)=0.88; Sa r(2)=0.95) and this was also true for N.
      gouldi in steady-state torpor (r(2)=0.93). During induced rewarming Tsub
      increased faster than Trec in both species. Our results demonstrate that
      transponders can be used to provide accurate remote measurement of Tb in two
      species of bats during different physiological states, both during steady-state
      conditions and throughout dynamic phases such as rewarming from torpor. We show
      that, at least during rewarming, regional heterothermy common to larger
      hibernators and other hibernating bats is also present in bats capable of daily
      torpor. 

PMID- 26300414
TI  - 'Hands-on' assessment: A useful strategy for improving patient safety in
      emergency departments.
AB  - BACKGROUND: Patient assessment is an essential nursing intervention that reduces
      the incidence and impact of errors and preventable adverse events in emergency
      departments (EDs). This paper reports on a key finding of the ED nurse component
      of a larger study investigating how registered nurses manage 'discontinuities' or
      'gaps' in patient care. METHODS: The larger study was undertaken as a
      naturalistic inquiry using a qualitative exploratory descriptive approach. Data
      were collected from a criterion-based purposeful sample of 71 nurses, of which 19
      were ED nurses, and analysed using content and thematic analysis strategies.
      RESULTS: The component of the study reported here revealed that ED nurses used
      'hands-on', head-to-toe assessment to manage gaps in patient care. Examination of
      the data revealed three key dimensions of patient assessment in the ED: (i)
      assessment is the 'bread and butter' of emergency nursing; (ii) 'hands-on'
      assessment techniques are irreplaceable and, (iii) patient assessment is
      undervalued in EDs. CONCLUSIONS: The findings of this study reaffirm the role of
      'hands-on' observation and assessment in creating safety in EDs. Further research
      and inquiry is needed to determine how health care systems can provide the
      conditions for ensuring that 'hands-on' assessment occurs.

PMID- 26300412
TI  - Upregulation of miR-497 induces hepatic insulin resistance in E3 rats with HFD
      MetS by targeting insulin receptor.
AB  - OBJECTIVE: The study aims to find regulatory microRNA(s) responsible for down
      regulated insulin receptor (InsR) in the liver of HFD-MetS E3 rats with insulin
      resistance. METHODS: Firstly, hepatic insulin resistance in HFD-MetS E3 rats was
      evaluated by RT-qPCR, western blotting, immunohistochemistry and PAS staining.
      Secondly, the candidate miRNAs targeting rat InsR were predicted through online
      softwares and detected in the liver of HFD-MetS E3 rats with insulin resistance.
      Then, the expression of InsR, phosphorylated IRS-1 (pIRS-1) at Tyr632,
      phosphorylated AKTs (pAKTs) at Ser473 and Thr308, phosphorylated GSK-3beta (p GSK
      3beta) at Ser9, phosphorylated GS (pGS) at Ser641 and the glycogen content were
      detected in CBRH-7919 cells treated with 100 nM insulin for different time
      periods by western blotting or PAS staining respectively, after transient
      transfection with miR-497 mimics or inhibitors for 24 h. Lastly, the relation
      between miR-497 and InsR was further determined using dual luciferase reporter
      assay. RESULTS: Elevated miR-497 was negatively related with down-regulated InsR
      in the liver of HFD-MetS E3 rats with insulin resistance. Comparing with the mNC
      group, glycogen content and the expression of InsR, pIRS-1 (Tyr632), pAKTs
      (Ser473 and Thr308) and pGSK-3beta (Ser9) decreased significantly in CBRH-7919
      cells, while pGS (Ser641) increased significantly, after transient transfection
      with miR-497 mimics for 24 h and treatment with 100 nM insulin for corresponding
      time periods, counter to those results in CBRH-7919 cells after similar
      procedures with miR-497 inhibitors and insulin. In addition, dual luciferase
      reporter assay further confirmed that miR-497 can bind to the 3'UTR of rat InsR.
      CONCLUSION: Insulin receptor is the target gene of miR-497, and elevated miR-497
      might induce hepatic insulin resistance in HFD-MetS E3 Rats through inhibiting
      the expression of insulin receptor and confining the activation of IRS
      1/PI3K/Akt/GSK-3beta/GS pathway to insulin.

PMID- 26300415
TI  - The effect of a staged, emergency department specific rapid response system on
      reporting of clinical deterioration.
AB  - BACKGROUND: Despite emerging evidence regarding clinical deterioration in
      emergency department (ED) patients, the widespread uptake of rapid response
      systems (RRS) in EDs has been limited. AIMS: To evaluate the effect of an ED RRS
      on reporting of clinical deterioration and determine if there were differences
      between patients who did, and did not, deteriorate during ED care. METHODS: A
      retrospective cross sectional design was used to conduct this single site study
      in Melbourne, Australia. Stratified random sampling identified 50 patients with
      shortness of breath, chest pain or abdominal pain per each year studied (2009
      2012) giving a total of 600 patients. The intervention was an ED RRS implemented
      in stages. RESULTS: The frequency of clinical deterioration was 14.8% (318
      episodes/89 patients). Unreported deterioration decreased each year (86.7%;
      68.8%; 55.3%; 54.0%, p=0.141). Patients who deteriorated during ED care had a
      longer median ED length of stay (2.8h; p<0.001), were 31.9% more likely to need
      hospital admission (p<0.001) and 4.9% more likely to die in hospital (p=0.044).
      CONCLUSIONS: A staged ED specific RRS decreased the frequency of unreported
      clinical deterioration. Controlled multi-site studies of ED specific RRSs are
      needed to examine the effect of formal ED RRSs on patient outcomes.

PMID- 26300416
TI  - Interactional behavior of the polyelectrolyte poly sodium 4-styrene sulphonate
      (NaPSS) with imidazolium based surface active ionic liquids in an aqueous medium.
AB  - The present study aims to develop an understanding of the interactions between an
      anionic polyelectrolyte, poly sodium 4-styrene sulphonate (NaPSS), and cationic
      surface active imidazolium based ionic liquids (SAILs), [Cnmim][Cl] (n = 10, 12,
      14) using a multi-technique approach. Various physicochemical and electrochemical
      techniques such as surface tension, conductivity, fluorescence, isothermal
      titration calorimetry (ITC), dynamic light scattering (DLS), turbidity,
      potentiometry, cyclic voltammetry (CV), and differential pulse voltammetry (DPV)
      are employed to obtain comprehensive information about NaPSS-SAIL interactions.
      Different stages of interaction, corresponding to the critical aggregation
      concentration (cac), critical saturation concentration (Cs) and critical micelle
      concentration (cmc) have been observed owing to the strong electrostatic and
      hydrophobic interactions, and the results obtained from different techniques
      complement each other very well. The results extracted from DLS and turbidity
      measurements clearly indicated that the size of the micelle like aggregates first
      decreases and then increases in the presence of polyelectrolyte. The binding
      isotherms obtained using potentiometry show a concentration dependence and the
      highly co-operative nature of the interactions which is attributed to aggregation
      of the polyelectrolyte-SAIL complexes. The diffusion coefficients (Dm) of the
      electroactive probe in the pure and NaPSS-SAIL mixed systems were obtained, which
      were further used to obtain the values of the micellar self-diffusion
      coefficients (D) and inter-micellar interaction parameters (kd). 

PMID- 26300417
TI  - Estimates of the incidence of actinomycosis in Colombia.

PMID- 26300418
TI  - Effect of Hydration on Healthy Intervertebral Disk Mechanical Stiffness.
AB  - The intervertebral disk has an excellent swelling capacity to absorb water, which
      is thought to be largely due to the high proteoglycan composition. Injury, aging,
      degeneration, and diurnal loading are all noted by a significant decrease in
      water content and tissue hydration. The objective of this study was to evaluate
      the effect of hydration, through osmotic loading, on tissue swelling and
      compressive stiffness of healthy intervertebral disks. The wet weight of nucleus
      pulposus (NP) and annulus fibrosus (AF) explants following swelling was 50% or
      greater, demonstrating significant ability to absorb water under all osmotic
      loading conditions (0.015 M-3.0 M phosphate buffered saline (PBS)). Estimated NP
      residual strains, calculated from the swelling ratio, were approximately 1.5 *
      greater than AF residual strains. Compressive stiffness increased with
      hyperosmotic loading, which is thought to be due to material compaction from
      osmotic-loading and the nonlinear mechanical behavior. Importantly, this study
      demonstrated that residual strains and material properties are greatly dependent
      on osmotic loading. The findings of this study support the notion that swelling
      properties from osmotic loading will be important for accurately describing the
      effect of degeneration and injury on disk mechanics. Furthermore, the tissue
      swelling will be an important consideration for developing biological repair
      strategies aimed at restoring mechanical behavior toward a healthy disk. 

PMID- 26300419
TI  - [Quality analytical specifications obtained by consensus through intercomparison
      programs AEFA/AEBM, SEQC y SEHH].

PMID- 26300420
TI  - [Patient satisfaction in the primary care clinic. Adjusting to times of crisis].

PMID- 26300421
TI  - Malnutrition in hospitals: What is the next course?

PMID- 26300422
TI  - Contribution of plastic waste recovery to greenhouse gas (GHG) savings in Spain.
AB  - This paper concentrates on the quantification of greenhouse gas (GHG) emissions
      of post-consumer plastic waste recovery (material or energy) by considering the
      influence of the plastic waste quality (high or low), the recycled plastic
      applications (virgin plastic substitution or non-plastic substitution) and the
      markets of recovered plastic (regional or global). The aim is to quantify the
      environmental consequences of different alternatives in order to evaluate
      opportunities and limitations to select the best and most feasible plastic waste
      recovery option to decrease the GHG emissions. The methodologies of material flow
      analysis (MFA) for a time period of thirteen years and consequential life cycle
      assessment (CLCA) have been integrated. The study focuses on Spain as a
      representative country for Europe. The results show that to improve resource
      efficiency and avoid more GHG emissions, the options for plastic waste management
      are dependent on the quality of the recovered plastic. The results also show that
      there is an increasing trend of exporting plastic waste for recycling, mainly to
      China, that reduces the GHG benefits from recycling, suggesting that a new focus
      should be introduced to take into account the split between local recycling and
      exporting. 

PMID- 26300423
TI  - Seasonal-like variation in song control system volume of wild zebra finches.
AB  - Zebra finches have been extensively used as a model system for studying the
      underlying neuroplasticity that allows for song learning during development.
      Zebra finches are considered age-limited or close-ended learners, in which fixed
      songs are learned within a certain window of time during development. In
      addition, they breed more or less continuously in laboratory conditions. As a
      consequence, less attention has been paid to potential neuroplasticity in adults.
      We present data on free-living zebra finches from two populations in Australia
      (one just beginning a period of breeding and another during a non-breeding
      period) that show a distinct difference in the volumes of two song system nuclei
      (HVC and Area X) depending on reproductive state. This is the first study to
      measure song system volumes in wild zebra finches, and suggests that the
      potential for neuroplasticity remains in adult zebra finches.

PMID- 26300424
TI  - HPV genotype distribution in older Danish women undergoing surgery due to
      cervical cancer.
AB  - INTRODUCTION: The prevalence of human papillomavirus (HPV)16/18 in cervical
      cancer may decrease with age. This study aimed to describe the HPV genotype
      distribution in Danish women aged 55 years or older with cervical cancer.
      MATERIAL AND METHODS: In this cross-sectional study we identified 153 cases of
      cervical cancer diagnosed at Aarhus University Hospital, Denmark (1990-2012) and
      Copenhagen University Hospital Herlev, Denmark (2007-2012). All women had surgery
      to treat the disease. HPV genotyping was performed on cervical cancer tissue
      using the INNO LiPA HPV genotyping extra (Fujirebio, Belgium) at the Department
      of Pathology, Aarhus University Hospital, Denmark. The main outcome was to
      estimate the age-specific prevalence of high-risk HPV genotypes included in the
      bivalent, the quadrivalent, and the nonavalent vaccine. RESULTS: Of 121 cases of
      cervical cancer included in this study, 113 were HPV-positive (93.4%). Although
      HPV16 and 18 were the most common genotypes overall, the prevalence of HPV16/18
      decreased significantly from 78.1% in women aged 55-59 years to 45.5% in women
      aged 75 or older (p < 0.001), whereas the prevalence of other HPV types and HPV
      negative cases tended to increase with age (p = 0.1). The prevalence of HPV types
      included in the nonavalent vaccine was stable around 90% until the age of 75
      years and then dropped to 63%. CONCLUSION: In the absence of waning immunity, the
      nonavalent HPV vaccine would be predicted to reduce cervical cancer burden in
      Denmark across a broader age-range compared with the reduced type-spectrum
      vaccines.

PMID- 26300425
TI  - Comparative analysis of primary hepatocellular carcinoma with single and multiple
      lesions by iTRAQ-based quantitative proteomics.
AB  - In clinical practices, the therapeutic outcomes and prognosis of hepatocellular
      carcinoma (HCC) patients with different tumor numbers after surgery are very
      different; however, the underlying mechanisms of the tumorigenesis and
      development of HCC with different tumor numbers are still not well understood.
      Here, we systematically compared the overall proteome profiles between the
      primary HCC with single and multiple lesions using iTRAQ-based quantitative
      proteomics approach. We identified that 107 and 330 proteins were dysregulated in
      HCC tissue with multiple lesions (MC group) and HCC tissue with a single lesion
      (SC group), compared with their non-cancerous tissue (MN and SN groups)
      respectively. The dysregulated proteins in MC group are concentrated in UBC
      signaling pathway and NFkappaB signaling pathway, but the dysregulated proteins
      in SC group are more concentrated in ERK signaling pathway and the NFkappaB
      signaling pathway. These information revealed that there might be different
      molecular mechanisms of the tumorigenesis and development of the HCC with single
      and multiple lesions. Furthermore, HSD17B13 were only down-regulated in MC group
      while HK2 were only up-regulated in SC group among these dysregulated proteins.
      Therefore, the protein HSD17B13 and HK2 might be potential biomarkers for the
      primary HCC with single and multiple lesions. 

PMID- 26300427
TI  - The animal-dependent risk factors in canine T-cell lymphomas.
AB  - Malignant lymphomas are one of the most common malignancies occurring in dogs;
      among them T-cell tumours are less commonly recognized. Recently, many authors
      have recommended cytology as a sufficient diagnostic method for canine lymphomas,
      especially if supported by immunocytochemistry or flow cytometry. The aim of the
      study was to characterize animal-dependent risk factors in canine T-cell
      lymphomas (TCLs) in Poland, including specific cytological subtypes.
      Determination of the type and subtype of the tumour was made based on the updated
      Kiel cytological classification adopted for dogs as previously described. Two
      breeds turned out predisposed to TCL (dog de Bordeaux and Boxer) while no
      predisposition to B-cell lymphoma could be evidenced. Dogs with low-grade
      lymphoma were significantly older than those with high-grade lymphoma.

PMID- 26300426
TI  - Umbilical cord blood-derived dendritic cells infected by adenovirus for SP17
      expression induce antigen-specific cytotoxic T cells against NSCLC cells.
AB  - Sperm protein 17 (SP17), a cancer/testis antigen, is expressed by non-small cell
      lung cancer (NSCLC). This study examined whether dendritic cells (DC) from human
      umbilical cord blood (UCB) could be induced for SP17 expression and induce
      antigen-specific CD8(+) cytotoxic T lymphocytes (CTLs) against NSCLC in vitro. We
      generated recombinant adenovirus of Ad-SP17 and control Ad-null. Infection with
      Ad-SP17, but not control, induced higher levels of SP17 expression in UCB-derived
      DC-Ad-SP17. Infection with Ad-SP17 significantly increased the frequency of
      CD80(+), CD83(+), CD86(+), and HLA-DR(+) DC that produced higher levels of IL-12,
      but lower IL-10. Co-culture of DC-Ad-SP17 with autologous UCB lymphocytes induced
      high frequency of IFNgamma(+) CD8(+) CTLs, which had selective cytotoxicity
      against SP17(+) lung cancer CRL-5922 cells in a HLA-I restrictive manner. Thus,
      UCB-derived DC modulated for SP17 expression induced antigen-specific anti-tumor
      immunity against SP17(+) NSCLC, and SP17 may be a valuable target for development
      of immunotherapy against SP17(+) NSCLC. 

PMID- 26300428
TI  - Infants Prefer Tunes Previously Introduced by Speakers of Their Native Language.
AB  - Infants show attentional biases for certain individuals over others based on
      various cues. However, the role of these biases in shaping infants' preferences
      and learning is not clear. This study asked whether infants' preference for
      native speakers (Kinzler, Dupoux, & Spelke, 2007) would modulate their
      preferences for tunes. After getting equal exposure to two different tunes
      introduced by two speakers, 7-month-olds (N = 32) listened longer to the tune
      that was introduced by a native speaker compared to the tune that was introduced
      by a foreign speaker. This suggests that the social-emotional context in which
      exposure to stimuli occurs influences auditory preferences, and that the early
      emerging attentional biases might have important ramifications regarding social
      learning in early infancy.

PMID- 26300429
TI  - Curcumin in Combination with Piperine Suppresses Osteoclastogenesis In Vitro.
AB  - INTRODUCTION: The dietary pigment curcumin is a natural polyphenol extracted from
      the Curcuma longa rhizomes native to South Asia. The antioxidative,
      antimicrobial, and anti-inflammatory activities besides its unknown side effects
      suggest that curcumin could be a promising antiresorptive agent to prevent
      replacement resorption in replanted teeth after traumatic avulsion. Piperine, an
      alkaloid present in black pepper, seems to enhance the bioavailability and
      activity of curcumin. Therefore, this study evaluated the biocompatibility of
      curcumin and piperine in cultures of periodontal ligament cells as well as their
      effects in an in vitro osteoclastogenesis model of RAW 264.7 macrophages.
      METHODS: The cytotoxicity in human periodontal ligament fibroblasts, human
      osteogenic sarcoma cells (SAOS-2), and murine osteoclastic precursors (RAW 264.7)
      was analyzed by using cell number determination and proliferation assays. The
      ability of curcumin and its conjugate to suppress the receptor activator of
      nuclear factor kappa B ligand-induced osteoclastogenesis was assessed by tartrate
      resistant acid phosphatase (TRAP) staining and activity as well as real-time
      polymerase chain reaction. RESULTS: Curcumin at concentrations >= 10 MUmol/L was
      cytotoxic in all cell types tested, whereas piperine showed only slight
      cytotoxicity at 30 MUmol/L in RAW and SAOS cultures. Although curcumin caused
      already significant effects, the combination with piperine completely suppressed
      the osteoclastogenesis by decreasing the TRAP activity and inhibiting the
      expression of the specific osteoclast markers TRAP, cathepsin K, and calcitonin
      receptor. CONCLUSIONS: We demonstrated that curcumin combined with piperine
      suppressed the osteoclastogenesis in vitro without causing cytotoxic effects in
      periodontal ligament cells. These findings suggest its potential therapeutic
      application for the prevention and treatment of replacement resorption in
      replanted avulsed teeth.

PMID- 26300430
TI  - Transcription factor co-occupied regions in the murine genome constitute T-helper
      cell subtype-specific enhancers.
AB  - Transcription factors (TFs) regulate cell-type-specific gene expression programs
      by combinatorial binding to cis-genomic elements, particularly enhancers,
      subsequently leading to the recruitment of cofactors, and the general
      transcriptional machinery to target genes. Using data integration of genome-wide
      TF binding profiles, we defined regions with combinatorial binding of lineage
      specific master TFs (T-BET, GATA3, and ROR-gammat) and STATs (STAT1 and STAT4,
      STAT6, and STAT3) in murine T helper (Th) 1, Th2, and Th17 cells, respectively.
      Stringently excluding promoter regions, we revealed precise genomic elements
      which were preferentially associated with the enhancer marks p300 and H3K4me1.
      Furthermore, closely adjacent TF co-occupied regions constituted larger enhancer
      domains in the respective Th-cell subset (177 in Th1, 141 in Th2, and 266 in Th17
      cells) with characteristics of so-called super-enhancers. Importantly, 89% of
      these super-enhancer regions were Th-cell subtype-specific. Genes associated with
      super-enhancers, including relevant Th-cell genes (such as Ifng in Th1, Il13 in
      Th2, and Il17a in Th17 cells), showed strong transcriptional activity.
      Altogether, the discovered catalog of enhancers provides information about
      crucial Th-cell subtype-specific regulatory hubs, which will be useful for
      revealing cell-type-specific gene regulation processes. 

PMID- 26300431
TI  - Effect of an Epineurial-Like Biohybrid Nerve Conduit on Nerve Regeneration.
AB  - A novel approach of making a biomimetic nerve conduit was established by seeding
      adipose-derived adult stem cells (ADSCs) on the external wall of porous poly(d,l
      lactic acid) (PLA) nerve conduits. The PLA conduits were fabricated using gas
      foaming salt and solvent-nonsolvent phase conversion. We examined the effect of
      two different porous structures (GS and GL) on ADSC growth and proliferation. The
      GS conduits had better structural stability, permeability, and porosity, as well
      as better cell viability at 4, 7, and 10 days. The epineurial-like tissue was
      grown from ADSC-seeded conduits cultured for 7 days in vitro and then implanted
      into 10-mm rat sciatic nerve defects for evaluation. The regeneration capacity
      and functional recovery were evaluated by histological staining,
      electrophysiology, walking track, and functional gait analysis after 6 weeks of
      implantation. Experimental data indicated that the autograft and ADSC-seeded GS
      conduits had better functional recovery than the blank conduits and ADSC-seeded
      GL conduits. The area of regenerated nerve and number of myelinated axons
      quantified based on the histology also indicated that the autograft and AGS
      groups performed better than the other two groups. We suggested that ADSCs may
      interact with endogenous Schwann cells and release neurotrophic factors to
      promote peripheral nerve regeneration. The design of the conduit may be critical
      for producing a biohybrid nerve conduit and to provide an epineurial-like
      support. 

PMID- 26300434
TI  - RPS Pharmacy Research UK Lecture Optimising medicines for older care home
      residents: now and the future.

PMID- 26300432
TI  - Use of double-stranded DNA mini-circles to characterize the covalent
      topoisomerase-DNA complex.
AB  - The enzymatic DNA relaxation requires the DNA to be transiently nicked and
      rejoined, the covalent topoisomerase-DNA complex being a key intermediate of the
      nicking-joining reaction. Practically, this reaction is most often characterized
      by oligonucleotides. However, the incision-religation of an oligonucleotide does
      not fully recapitulate the incision-religation occuring during relaxation and the
      preferred substrate for such reaction characterization is supercoiled DNA. We
      therefore developed a method that used radiolabeled supercoiled DNA mini-circles
      to characterize the covalent enzyme-DNA complex formed during a relaxation
      reaction. Resolution of the relaxation products under different conditions
      permitted to quantify the proportion of covalent complex formed during the
      relaxation catalyzed by two topoisomerase models, the Escherichia coli
      topoisomerase I and the calf thymus topoisomerase I. As expected, the covalent
      complex formed with the calf thymus topoisomerase I was significantly enriched by
      camptothecin, a widely-used inhibitor of this topoisomerase, and a salt jump
      permitted the multiple topoisomerases trapped per mini-circle to complete the
      reaction cycle. The identified positions of the camptothecin-induced incision
      sites were shown to be independent of the linking number and the substrate
      circular nature Overall, our results demonstrate that supercoiled mini-circles
      constitute a powerful and polyvalent substrate to characterize the mechanism of
      action of novel topoisomerases and inhibitors, including the incision-religation
      reaction. 

PMID- 26300436
TI  - A lesson learned from the MERS epidemic in Korea: an essay on MERS.

PMID- 26300435
TI  - Monitoring targets and indicators for the prevention and control of non
      communicable diseases in Korea.
AB  - In order to respond to the increasing burden of non-communicable diseases (NCDs)
      worldwide, the World Health Organization developed the global action plan (GAP),
      which included nine targets and 25 indicators to monitor the targets. Owing to
      space constraints, the article reviewed the status of 17 indicators for seven
      targets out of nine targets in the GAP in Korea. Most of these 17 indicators
      required additional analysis with existing national data to evaluate the status
      in Korea. Based on the result from evaluating indicators, the current NCD policy
      strategy and resources in Korea seemed unlikely to reach the GAP goals, unless
      innovative policy changes was planned to reduce NCD risk factors particularly
      focusing on smoking, excessive drinking, and insufficient physical activity. 

PMID- 26300437
TI  - Surveillance operation for the 141st confirmed case of Middle East Respiratory
      Syndrome coronavirus in response to the patient's prior travel to Jeju Island.
AB  - The provincial government of Jeju, South Korea, was notified that a 42-year-old
      man infected with the Middle East Respiratory Syndrome (MERS) coronavirus had
      gone sightseeing in Jeju Island. Although the visiting period might be
      interpreted as the incubation period of MERS, the province decided to conduct
      active surveillance to prevent a worst-case scenario. Based on the channel of
      movement of the patient, healthy isolation and active monitoring were conducted
      for persons who came in contact with the patient. During the active surveillance,
      none of the 56 persons in self-isolation and 123 persons under active monitoring
      became infected. This fact supports that MERS is not contagious during the
      incubation period. 

PMID- 26300438
TI  - Elevation of serum surfactant protein-A with exacerbation in canine eosinophilic
      pneumonia.
AB  - A 7-year-old female spayed Labrador Retriever was admitted to our hospital,
      because of cough with sputum. She was diagnosed as having canine eosinophilic
      pneumonia (CEP) based on blood eosinophilia, bronchial pattern and infiltrative
      shadow observed on thoracic radiography, bronchiolar obstruction and air-space
      consolidation predominantly affecting the right caudal lung lobe, as revealed by
      computed tomography (CT), predominant eosinophils in CT-guided fine needle
      aspiration and the clinical course. She exhibited a good response to steroid
      therapy, and the cough disappeared. The serum surfactant protein (SP)-A level
      increased with the aggravated symptom and decreased markedly with improvement
      compared with the C-reactive protein level and the number of eosinophils. We
      propose that serum SP-A level is a good biomarker in CEP. 

PMID- 26300439
TI  - Expression of NG2 proteoglycan in the degenerated intervertebral disc in
      dachshunds.
AB  - The pathogenesis of intervertebral disc (IVD) degeneration is not fully
      understood. The biomolecular signaling pathways involved in the IVD degeneration
      require further investigation. The aim of this study was to investigate the
      expression of NG2 proteoglycan in the degenerated IVD. IVD samples were obtained
      from 16 Dachshunds that were confirmed to have IVD herniation and subsequently
      underwent hemilaminectomy. The samples were subjected to histological and
      immunohistochemical (IHC) examinations. IHC revealed positive results for the
      expression of NG2 proteoglycan in all examined samples. The results showed the
      expression of NG2 proteoglycan by the degenerated IVDs. 

PMID- 26300440
TI  - Development of a genotyping tool for a functionally relevant CYP2C19 allele
      (Phe100Asn, Ala103Val and Ile112Leu) in cynomolgus macaques.
AB  - .In cynomolgus macaques, which are widely used in drug metabolism studies,
      CYP2C19 (formerly known as CYP2C75) is abundantly expressed in liver, metabolizes
      human CYP2C substrates and is thus an important drug-metabolizing enzyme. One of
      the cynomolgus CYP2C19 alleles (p.Phe100Asn, p.Ala103Val and p.Ile112Leu) results
      in substantially reduced metabolic activity and thus is an important allele in
      drug metabolism studies. For this allele, a genotyping tool was developed using
      allele-specific TaqMan probe. Genotyping 40 Cambodian cynomolgus macaques using
      this tool found 1 homozygote, 17 heterozygotes and 22 wild type animals, and the
      result was confirmed by direct-sequencing. Interestingly, this allele frequency
      was similar to that of Chinese cynomolgus macaques. The genotyping tool
      established is useful for drug metabolism studies using cynomolgus macaques. 

PMID- 26300441
TI  - Between-domain cognitive dispersion and functional abilities in older adults.
AB  - OBJECTIVE: Within-person variability in cognitive performance is related to
      neurological integrity, but the association with functional abilities is less
      clear. The primary aim of this study was to examine the association between
      cognitive dispersion, or within-person variability, and everyday multitasking and
      the way in which these variables may influence performance on a naturalistic
      assessment of functional abilities. METHOD: Participants were 156 community
      dwelling adults, age 50 or older. Cognitive dispersion was calculated by
      measuring within-person variability in cognitive domains, established through
      principal components analysis. Path analysis was used to determine the
      independent contribution of cognitive dispersion to functional ability, mediated
      by multitasking. RESULTS: Results of the path analysis revealed that the number
      of subtasks interweaved (i.e., multitasked) mediated the association between
      cognitive dispersion and task sequencing and accuracy. Although increased
      multitasking was associated with worse task performance in the path model,
      secondary analyses revealed that for individuals with low cognitive dispersion,
      increased multitasking was associated with better task performance, whereas for
      those with higher levels of dispersion multitasking was negatively correlated
      with task performance. CONCLUSION: These results suggest that cognitive
      dispersion between domains may be a useful indicator of multitasking and daily
      living skills among older adults.

PMID- 26300442
TI  - Apigenin inhibits the proliferation of adenoid cystic carcinoma via suppression
      of glucose transporter-1.
AB  - Apigenin is a natural phyto-oestrogen flavonoid, which exerts various biological
      effects, including anti-oxidative, anti-inflammatory and anticancer activities.
      In addition, apigenin has recently been reported to target hypoxic markers;
      however, there are currently no studies regarding the association between
      apigenin and glucose transporter-1 (GLUT-1) in adenoid cystic carcinoma (ACC).
      The present study investigated whether apigenin inhibits the proliferation of ACC
      cells or suppresses the expression of GLUT-1 in ACC cells. The results of the
      present study demonstrated that apigenin inhibits ACC-2 cell growth in a dose-
      and time-dependent manner. Treatment with apigenin also induced apoptosis and
      G2/M-phase arrest in a dose- and time-dependent manner. Corresponding with the
      above results, the expression levels of GLUT-1 were significantly decreased
      following treatment in a dose- and time-dependent manner. These results suggest
      that the inhibition of ACC-2 cell growth by apigenin may be due to the decreased
      expression of GLUT-1. 

PMID- 26300444
TI  - A highly enantioselective, organocatalytic [3+2]-cycloannulation reaction towards
      the de novo-synthesis of 1-cyclopentenyl-alpha-keto esters.
AB  - We disclose herein a highly enantioselective de novo-synthesis of chiral 1
      cyclopentenyl-alpha-keto esters starting from a simple bis-silyl-1,3-dienediolate
      and alpha,beta-unsaturated aldehydes via a domino vinylogous Michael
      intramolecular Knoevenagel-type condensation. The cyclopentenes proved to be
      highly versatile and were readily converted into various structural motifs. 

PMID- 26300443
TI  - Association of Single Nucleotide Polymorphisms in STAT3 with Hand-Foot Skin
      Reactions in Patients with Metastatic Renal Cell Carcinoma Treated with Multiple
      Tyrosine Kinase Inhibitors: A Retrospective Analysis in Japanese Patients.
AB  - BACKGROUND: Signal transducer and activator of transcription (STAT)3 is a
      reported mediator of molecular-targeted drug-induced keratinocyte toxicity. AIM:
      Our purpose was to assess the association of single nucleotide polymorphisms
      (SNPs) in STAT3 with hand-foot skin reactions (HFSR) in patients with metastatic
      renal cell carcinoma (mRCC) treated with multiple tyrosine kinase inhibitors
      (mTKIs). PATIENTS AND METHODS: Sixty-five Japanese patients with clear cell renal
      cell carcinoma who were treated with any mTKI at Kobe University Hospital were
      retrospectively genotyped to elucidate a potential association between STAT3
      polymorphisms and HFSR development. RESULTS: The final analysis included 60
      patients. HFSR was observed in 46 patients. The GG, GC, and CC genotypes at
      rs4796793 were found in 9, 27, and 24 patients, respectively. Three other STAT3
      polymorphisms exhibited tight linkage disequilibrium with rs4796793. A
      significant association was found between the rs4796793 allele and HFSR [G vs. C;
      odds ratio [OR], 4.33; 95 % confidence interval [CI], 1.80-10.45; P = 0.001]. The
      GG genotype had the highest OR compared with GC + CC genotypes (OR, 10.75; 95 %
      CI, 2.38-48.07; P = 0.001). In a time-to-event Kaplan-Meier analysis, a
      statistically significant difference was observed between the GC + CC and the GG
      genotypes (P = 0.009). CONCLUSIONS: The rs4796793 genotype appears to be a novel
      factor for mTKI-induced HFSR in patients with mRCC. Prospective translational
      trials with larger numbers of patients are required to confirm our results. This
      research suggests a potential benefit of STAT3 polymorphism screening in patients
      treated with mTKIs.

PMID- 26300445
TI  - Preparation and characterization of bioadhesive controlled-release gels of
      cidofovir for vaginal delivery.
AB  - The aim of this study was to develop mucoadhesive and thermosensitive gels for
      vaginal delivery that would be able to provide a controlled release of the model
      drug, cidofovir. The study also monitored the drug's potential antiviral
      properties. Cidofovir was put into the form of a vaginal gel, using mucoadhesive
      and thermosensitive polymers such as chitosan, Carbopol 974P, HPMC, and poloxamer
      407. The physicopharmaceutical properties and stability of the vaginal gel
      formulations were evaluated. The gel formulation which was prepared with HPMC
      K100M exhibited the highest viscosity, as well as maximum adhesiveness,
      cohesiveness, and mucoadhesion values. The results of antiviral activity studies,
      which used the bovine herpes virus type 1 virus infection in vitro model using
      Vero cells, demonstrated the antiherpetic effect of the cidofovir gel containing
      HPMC K100M, at least under in vitro conditions. The study found that a
      mucoadhesive vaginal gel containing cidofovir can be a promising and innovative
      alternative therapeutic system for the treatment of genital herpes simplex virus
      and human papilloma virus induced infections in women. 

PMID- 26300446
TI  - Oleophobicity of Biomimetic Micropatterned Surface and Its Effect on the Adhesion
      of Frozen Oil.
AB  - The relationship between the oleophobicity of micropatterned surfaces and the
      reduction of oil adhesion at low temperatures was explored by using siloxane
      elastomer surfaces as a model system. Polydimethylsiloxane (PDMS) surfaces were
      fabricated with varying oleophobicity from oleophilic to superoleophobic by
      combing the blending of trichloro(1H,1H,2H,2H-perfluorooctyl)silane (FDTS) into
      PDMS with the construction of bioinspired micropillars. The oil contact angles of
      micropillars were >130 degrees , with the largest contact angle measured to be
      146 degrees . The micropillared surface showed remarkable self-cleaning
      properties; the contact angle hysteresis was <15 degrees . The transparent oil
      droplets on PDMS surfaces of varied oleophobicity were frozen into a white
      colored solid at -25  degrees C with the aid of a cooling system. Adhesion forces
      of the frozen oil droplets were obtained from the knock-off tests, showing that
      the adhesion forces dropped with the increased oleophobicity. The largest
      adhesion force was observed on the oleophilic flat surface, while the lowest
      adhesion force was on the highest oleophobic micropillared surface. The relative
      effectiveness of chemical and physical modifications on adhesion strength
      reduction was studied in terms of FDTS and micropillars, respectively. The
      results showed that a reduction of adhesion strength by 4% was reached by
      blending FDTS into flat PDMS, while a much more pronounced reduction of frozen
      oil adhesion strength by 60% was achieved by blending FDTS into PDMS
      micropillars; these results suggested a possible synergic effect of the FDTS
      chemistry and micropillar on the reduction of adhesion strength of frozen oil
      droplets. 

PMID- 26300447
TI  - Irf4 Regulates the Choice between T Lymphoid-Primed Progenitor and Myeloid
      Lineage Fates during Embryogenesis.
AB  - T lymphoid-primed progenitors are hematopoietic progenitors destined to enter the
      thymus. The in vivo characterization of these embryonic progenitors is
      challenging, however, due to the intrauterine development of mouse embryos. Thus,
      how the fate of these cells is determined has not been fully defined in mammals.
      Here we use zebrafish embryos to show that the homing of T lymphoid-primed
      progenitors to the thymus is impaired, concomitant with a decrease in ccr9a
      expression, in the absence of irf4a. Strikingly, fate mapping assays at the
      single-cell level showed a fate change of irf4a-deficient T lymphoid-primed
      progenitors to myeloid cells, accompanied by an increase in Pu.1 expression.
      These data indicate that in addition to regulating ccr9a expression, Irf4a is
      essential in T lymphoid-primed progenitors for repressing Pu.1 expression to
      prevent an alternate fate. Our findings provide insight into the fate
      determination mechanism of T lymphoid-primed progenitors.

PMID- 26300448
TI  - Mitotic Membrane Turnover Coordinates Differential Induction of the Heart
      Progenitor Lineage.
AB  - In response to microenvironmental cues, embryonic cells form adhesive signaling
      compartments that influence survival and patterning. Dividing cells detach from
      the surrounding matrix and initiate extensive membrane remodeling, but the in
      vivo impact of mitosis on adhesion-dependent signaling remains poorly
      characterized. We investigate in vivo signaling dynamics using the invertebrate
      chordate, Ciona intestinalis. In Ciona, matrix adhesion polarizes fibroblast
      growth factor (FGF)-dependent heart progenitor induction. Here, we show that
      adhesion inhibits mitotic FGF receptor internalization, leading to receptor
      enrichment along adherent membranes. Targeted disruption of matrix adhesion
      promotes uniform FGF receptor internalization and degradation while enhanced
      adhesion suppresses degradation. Chimeric analysis indicates that integrin beta
      chain-specific impacts on induction are dictated by distinct internalization
      motifs. We also found that matrix adhesion impacts receptor enrichment through
      Caveolin-rich membrane domains. These results redefine the relationship between
      cell division and adhesive signaling, revealing how mitotic membrane turnover
      orchestrates adhesion-dependent signal polarization.

PMID- 26300449
TI  - Domino Heck/borylation sequence towards indolinone-3-methyl boronic esters:
      trapping of the sigma-alkylpalladium intermediate with boron.
AB  - Pd-catalyzed domino Heck/borylation of acrylamides with B2pin2 is reported to
      generate synthetically useful indolinone-3-methyl boronic esters, via capturing
      sigma-alkyl palladium with boron. Further functionalization of the obtained
      boronic ester qualify it as a new starting point for the functionalization of
      specific C(sp(3))-H bond. Moreover, the application of an Ugi-adduct as starting
      material or B2nep2 as an alternative boron source works equally well, making this
      a broadly applicable and robust method for the formation of a C-C and C-B bond in
      a single operation. 

PMID- 26300450
TI  - The relevance of fractional amplitude of low-frequency fluctuation to
      interference effect.
AB  - Growing evidence has indicated a potential connection between resting-state
      functional magnetic resonance imaging (RS-fMRI) signal and cognitive performance.
      However, the relationship between intrinsic neural activity and behavioral
      interference effect on cognitive control has been poorly understood. In the
      present study, seventy-eight healthy subjects underwent RS-fMRI and performed
      Multi-Source Interference Task (MSIT). The fractional amplitude of low-frequency
      fluctuation (fALFF) was measured as an indicator of intrinsic brain activity. The
      difference in reaction times between interference and control conditions in MSIT
      was evaluated as interference effect. Then we examined the associations between
      fALFF and interference effect using partial correlation analysis controlling for
      age, gender and mean framewise displacement. The results demonstrated that fALFF
      values in orbital prefrontal cortex (OPFC) and right inferior frontal cortex
      (IFC) were negatively correlated with the interference effect in MSIT. The
      findings manifest that OPFC and right IFC may influence the processing efficiency
      of cognitive conflict and play a crucial role in cognitive control. 

PMID- 26300451
TI  - Dopamine and glutamate release in the anterior default system during rest: A
      monkey microdialysis study.
AB  - Human neuroimaging studies have demonstrated the presence of a default system in
      the brain, which shows a default mode of brain activity, i.e., greater activity
      during rest than during an attention-demanding cognitive task. Our previous study
      on monkeys has revealed a default mode of brain activity in medial cortical
      areas. We have observed an increase in dopamine (DA) release during a working
      memory (WM) task compared with that during rest in the monkey lateral prefrontal
      cortex (LPFC). However, no previous study has examined DA release related to the
      default mode of brain activity. We used a microdialysis technique to investigate
      changes in DA release in the medial prefrontal cortex (MPFC), which constitutes
      the anterior default system, during the WM task and rest. Because DA and
      glutamate (Glu) release in the LPFC is interrelated, we also examined Glu release
      in the MPFC. We observed a significant increase in DA release, but no significant
      change in Glu release during rest compared with that during the WM task. We also
      observed an inhibitory relationship between the two transmitters in the MPFC.
      Considering that human default brain activity is related to internal thought
      processes and increased DA release in the LPFC plays an important role in
      executive control, increase in DA release during rest in the monkey anterior
      default system may be related to some form of internal thought process. 

PMID- 26300452
TI  - Stress during the gestational period modifies pups' emotionality parameters and
      favors preference for morphine in adolescent rats.
AB  - Experimental animal studies have shown that early life periods are highly
      vulnerable to environmental factors, which may exert prolonged impact on HPA axis
      function and on subsequent neurochemical and behavioral responses in adulthood.
      Here we evaluated the influence of environmental stressful situations in two
      different early life stages on stress-related behaviors, and morphine-conditioned
      place preference (CPP), which is indicative of addiction. While in the
      gestational stress (Gest-S) dams were exposed to daily sessions of chronic mild
      stress (CMS) for 2 weeks, in the postnatal stress (post-NS) the offspring were
      exposed daily to neonatal isolation from postnatal day (PND) 2 to PND 9 for 60
      min. Animals exposed to post-NS showed lesser anxiety in different behavioral
      paradigms (elevated plus maze-EPM and defensive burying test-DBT) as well as
      increased exploratory behavior (open-field task-OFT), and no preference for
      morphine in CPP. In contrast, animals exposed to Gest-S showed increased
      corticosterone plasma levels together with anxiety symptoms and greater
      preference for morphine following three days of drug withdrawal. Our findings
      indicate that the gestational period is critical for stress, whose effects may be
      manifest throughout life. On the other hand, post-NS can trigger neuroadaptations
      able to overcome emotional consequences of early life. We hypothesized that Gest
      S is able to modify responses to opioids along adulthood, which may facilitate
      development of addiction to these drugs.

PMID- 26300453
TI  - Different attentional abilities among inbred mice strains using virtual object
      recognition task (VORT): SNAP25+/- mice as a model of attentional deficit.
AB  - Autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD),
      schizophrenia, Alzheimer's and Parkinson's disease are characterized by
      attentional deficits. In the present study we first applied the virtual object
      recognition test (VORT), where 3D objects were replaced with highly discriminated
      geometrical shapes and presented on two 3.5-inch widescreen displays, in
      different inbred mice strains (C57BL/6N, DBA/2J, BALB/cJ), in comparison with the
      standard object recognition test (NOR). In both NOR and VORT, there was a
      progressive decay of performance in terms of reduced discrimination index from 5
      min to 72 h of inter-trial delay in all strains. However, BALB/cJ inbred mice
      showed a better long lasting performance than C57BL/6N and DBA/2J, when tested in
      NOR. In VORT, BALB/cJ showed the best performance. Total exploration time was
      always higher in BALB/cJ than C57BL/6N and DBA/2J mice. C57BL/6N were less
      explorative strain than DBA/2J and BALB/cJ mice. When VORT was applied to SNAP
      25(+/-) mice, an impairment in both NOR and VORT was shown. However, when moving
      shapes were applied, these heterozygous mice improved their performance,
      suggesting that the introduction of motion is a strong cue that makes the task
      more valuable to study attention deficits. Taken together, these data indicate
      that VORT provides a useful and rapid tool to identify the attentional deficit in
      different inbred strains and genetically modified mice, enhancing the value of
      psychiatric mouse models.

PMID- 26300454
TI  - The role of computer assisted navigation in revision surgery for failed anterior
      cruciate ligament reconstruction of the knee: A continuous series of 52 cases.
AB  - INTRODUCTION: The causes of failure of anterior cruciate ligament (ACL)
      reconstruction mainly involve incorrect tunnel positioning. There is no
      intraoperative tool allowing the surgeon to test graft biomechanics and to
      confirm that the new graft is in an optimal position. HYPOTHESIS: Control is
      improved with computer assisted navigation. MATERIAL AND METHODS: In this
      retrospective study, revision ACL reconstruction was performed with a new
      autologous graft in a continuous series of 52 failed ACL reconstructions. A
      computer assisted navigation system was used intraoperatively in all knees.
      Evaluation with this system confirmed the position of old and new tunnels as well
      as intraoperative laxity. RESULTS: Evaluation of tunnel position based on
      traditional radiological criteria found in the literature significantly
      underestimated graft biomechanics: 69% of the cases presented with unfavorable
      graft ansiometry (mean: 13 +/- 2.2mm) while the correct position of the tibial
      tunnel was identified in 64% of cases on radiography and the femoral tunnel in
      48%. All new grafts were optimally positioned by the computer assisted navigation
      system with a mean isometery of 3.2 (+/- 0.7) mm. Comparative pre- and
      postoperative evaluation of laxity showed a statistically significant improvement
      (P < 0.001): preoperative and postoperative Lachman test: 10.5 +/- 2 mm and 3 +/-
      0.5, respectively; global rotational laxity: 24 +/- 5 degrees  and 37 +/- 7
      degrees  respectively. CONCLUSION: The use of a computer assisted navigation
      system allows optimal positioning of the graft as well as a predictive assessment
      of laxity.

PMID- 26300455
TI  - Comparison of the reliability of leg length and offset data generated by three
      hip replacement CAOS systems using EOSTM imaging.
AB  - INTRODUCTION: Computer-assisted orthopaedic surgery (CAOS) theoretically will
      help to optimise total hip arthroplasty (THA) results. Although CAOS systems have
      become more sophisticated, they are not widely used, partially because of their
      suspect reliability. To assess reliability of these systems, we carried out a
      study with multiple objectives in mind: (1) establish and compare the accuracy of
      the leg length (LL) measurement from three CAOS systems; (2) analyse the
      correlation of LL and offset data generated by these CAOS systems with those of
      the EOSTM imaging system; (3) determine if the goals of leg length restoration
      with +/-2 and +/-5 mm were achieved; (4) evaluate why certain cases fails.
      HYPOTHESIS: The three CAOS systems have the same accuracy for LL, and their error
      is less than or equal to 0.6mm. MATERIAL AND METHODS: We retrospectively studied
      106 cases of primary THA where preoperative and postoperative measures of leg
      length had been performed with an EOSTM imaging system. The cases were placed in
      three groups, depending on which CAOS system had been used: group A
      (AmplivisionTM, amplitude), group B (Hip ExpressTM, Brainlab), group P (THSTM,
      Praxim). The accuracy of the leg length data was calculated by finding the
      difference between the data from each CAOS system and the gold-standard EOS
      measurements. RESULTS: The leg length accuracy was -0.846 [-5 to 9], -0.675 [-9
      to 18] and 0.542 mm [-5 to 13], respectively for groups A, B and P. The accuracy
      was significantly lower in group A than B (P=0.044) and group P (P=0.038). The
      Pearson correlation coefficient for CAOS and EOS measurements was 0.189, 0.701
      and 0.891 for leg length and 0.668, 0.202 and 0.680 for offset, for groups A, B
      and P, respectively. No difference between groups were observed relative to the
      leg length objectives being achieved within +/-2 mm (P=0.61) and +/-5 mm
      (P=0.314). There were no differences in terms of the number of CAOS failures:
      three in group A, one in group B and three in group P (P=0.06). CONCLUSION: The
      PraximTM and BrainlabTM CAOS systems had similar accuracy for leg length
      measurements, and both were better than the AmplitudeTM system. Only the PraximTM
      had an error of less than 0.6mm. All the CAOS systems had values less than 1mm,
      which is considered excellent. LEVEL OF EVIDENCE: Level IV, retrospective study.

PMID- 26300456
TI  - Primary cup stability in THA with augmentation of acetabular defect. A comparison
      of healthy and osteoporotic bone.
AB  - BACKGROUND CONTEXT: Reconstruction of acetabular defect has been advocated as
      standard procedure in total hip arthroplasty. The presence of bony defects at the
      acetabulum is viewed as a cause of instability and acetabular wall augmentation
      is often used without proper consideration of surrounding bone density. The
      initial cup-bone stability is, however, a challenge and a number of studies
      supported by clinical follow-ups of patients suggested that if the structural
      graft needs supporting more than 50% of the acetabular component, a
      reconstruction cage device spanning ilium to ischium should be preferred to
      protect the graft and provide structural stability. This study aims to (1)
      investigate the relationship between cup motion and bone density and (2) quantify
      the re-distribution of stress at the defect site after augmentation. HYPHOTESIS:
      Paprosky type I or II, acetabular defects, when reconstructed with bone screws
      supported by bioabsorbable calcified triglyceride bone cement are significantly
      less effective for osteoporotic bone than healthy bone. MATERIALS AND METHODS:
      Acetabular wall defects were reconstructed on six cadaveric subjects with
      bioabsorbable calcified triglyceride bone cement using a re-bar technique. Data
      of the specimen with higher bone density was used to validate a Finite Element
      Model. Values of bone apparent density ranging from healthy to osteoporotic were
      simulated to evaluate (1) the cup motion, through both displacement and rotation,
      (2) and the von Mises stress distribution. RESULTS: Defect reconstruction with
      bone screws and bioabsorbable calcified triglyceride bone cement results in a re
      distribution of stress at the defect site. For a reduction of 65% in bone
      density, the cup displacement was similar to a healthy bone for loads not
      exceeding 300 N, as load progressed up to 1500 N, the reconstructed defect showed
      increase of 99 MUm (128%) in displacement and of 0.08 degrees  in rotation angle.
      CONCLUSIONS: Based on the results, we suggest that an alternative solution to
      wall defect augmentation with bone screws supported by bioabsorbable calcified
      triglyceride bone cement, be used for osteoporotic bone. LEVEL OF EVIDENCE: Level
      IV, experimental and cadaveric study.

PMID- 26300457
TI  - Recommendations for the use of long-term central venous catheter (CVC) in
      children with hemato-oncological disorders: management of CVC-related occlusion
      and CVC-related thrombosis. On behalf of the coagulation defects working group
      and the supportive therapy working group of the Italian Association of Pediatric
      Hematology and Oncology (AIEOP).
AB  - Central venous catheters (CVC), used for the management of children with hemato
      oncological disorders, are burdened by a significant incidence of mechanical,
      infective, or thrombotic complications. These complications favor an increasing
      risk in prolongation of hospitalization, extra costs of care, and sometimes
      severe life-threatening events. No guidelines for the management of CVC-related
      occlusion and CVC-related thrombosis are available for children. To this aim,
      members of the coagulation defects working group and the supportive therapy
      working group of the Italian Association of Pediatric Hematology and Oncology
      (AIEOP) reviewed the pediatric and adult literature to propose the first
      recommendations for the management of CVC-related occlusion and CVC-related
      thrombosis in children with hemato-oncological disorders. 

PMID- 26300458
TI  - Predicting the characteristics of the aetiological agent for Kawasaki disease
      from other paediatric infectious diseases in Japan--ERRATUM.
AB  - In the above-mentioned article [1] there is an error in the penultimate heading
      in Table 4. The heading 'T predicted by equation (2)' should read 'T predicted by
      equation (7)'.

PMID- 26300459
TI  - Modified back wall first artery anastomosis technique in living donor liver
      transplantation.
AB  - BACKGROUND/OBJECTIVES: Back wall technique is usually used for hepatic artery
      anastomosis in living donor liver-transplantation. In this technique, two
      stitches are placed in the two corners of the artery wall initially and the
      microclamp on the artery is rotated to place the sutures to the back wall first.
      In some cases, the microclamp cannot be rotated because of insufficient length of
      the graft or recipient artery. If this occurs, it may be difficult to rotate the
      artery to perform the back wall artery anastomosis technique. In these cases, the
      difficulty of performing the anastomosis can cause intimal tears. Thus, we prefer
      a modified technique for artery anastomosis in such situations. METHODS: In this
      modified technique, two stitches are placed in the middle of the posterior wall
      and middle of the anterior wall initially. The artery is twisted 90 degrees  to
      the right side and to the left side respectively, instead of one 180 degrees 
      rotation, to place the back wall stitches. CONCLUSION: In this modified
      technique, reversing the microclamp is eliminated that can cause intimal damage.
      Therefore, it may be superior to the conventional method in terms of reducing the
      difficulty of performing anastomosis and intimal damage to the vessels.

PMID- 26300460
TI  - Fabrication of redox-responsive magnetic protein microcapsules from hen egg white
      by the sonochemical method.
AB  - Redox-responsive magnetic protein microcapsules with Fe3O4 magnetic nanoparticles
      (MNPs) encapsulated inside have been obtained using a facile, cost-effective and
      fast sonochemical method from hen egg white proteins. Such prepared redox
      responsive magnetic hen egg white protein microcapsules (MHEWPMCs) could be
      easily manipulated to do magnetic-guided targeting delivery. The synchronous
      loading of the hydrophobic dye Coumarin 6 as a model of drug into MHEWPMCs was
      readily achieved during the fabrication of MHEWPMCs by dissolving them into the
      oil phase before ultrasonication. TEM images indicated that Fe3O4 MNPs were
      encapsulated in MHEWPMCs. Confocal laser scanning microscopic images indicated
      that the dye was distributed evenly in the MHEWPMCs and no leakage of dye from
      the MHEWPMCs was observed due to the protection of protein shells. The MHEWPMCs
      are potential candidates as attractive carriers for drug targeting delivery and
      stimuli-responsive release due to their magnetic and redox responsiveness of the
      disulfide in the microcapsule shells. 

PMID- 26300462
TI  - Vocal cord dysfunction: asking the right questions.

PMID- 26300464
TI  - A randomized trial comparing simultaneous vs. sequential field treatment of
      actinic keratosis with ingenol mebutate on two separate areas of the head and
      body.
AB  - BACKGROUND: Actinic keratoses (AKs) are precursors to invasive squamous cell
      carcinoma and can progress if untreated. Limited data support the use of ingenol
      mebutate to treat AKs on more than one area of the body simultaneously.
      OBJECTIVE: To investigate safety, efficacy and treatment satisfaction when
      treating separate areas simultaneously or sequentially with different
      concentrations of ingenol mebutate gel. METHODS: In this phase IIIb study
      (NCT01787383), patients with clinically visible, non-hyperkeratotic AKs on two
      separate treatment areas (face/scalp and trunk/extremities) were randomized to
      simultaneous or sequential treatment with ingenol mebutate gel (0.015% and
      0.05%). Endpoints included composite local skin response (LSR) score 3 days after
      first application, complete AK clearance and percentage reduction in AKs at week
      8. RESULTS: There were no statistically significant differences between
      simultaneous (n = 101) and sequential (n = 98) groups in composite LSR score
      (10.4 vs. 9.7), complete clearance (52.7% vs. 46.9%) or percentage reduction in
      AKs (83.4% vs. 79.1%). Mean composite LSR scores on face/scalp and
      trunk/extremities were similar for both groups. Adverse event (AE) incidence was
      comparable between groups, the most common treatment-related AEs being pruritus
      and pain at the application site. CONCLUSION: Treating AKs with ingenol mebutate
      simultaneously or sequentially gave similar results in terms of tolerability (LSR
      score, AEs) and efficacy (complete clearance). Therefore, the physician and
      patient can select the most convenient treatment regimen, with confidence in
      achieving a similar outcome.

PMID- 26300465
TI  - Serum levels of immunoglobulins G1 and G4 targeting the non-collagenous 16A
      domain of BP180 reflect bullous pemphigoid activity and predict bad prognosis.
AB  - Bullous pemphigoid (BP) is an autoimmune subepidermal bullous disease, and
      different immunoglobulin (Ig)G autoantibody subclasses may play different roles
      in the pathogenesis of BP. This study aims to evaluate the relationship between
      specific IgG subclasses and BP. Enzyme-linked immunoassays (ELISA) were developed
      to test the IgG subclasses targeting the non-collagenous 16A (NC16A) domain of
      BP180. A statistical analysis was carried out to assess the relationship of BP
      and IgG subclasses as well as other factors. The correlation coefficients between
      the ELISA scores for four IgG subclasses and disease severity scores were 0.586
      for IgG, 0.441 for IgG1, 0.594 for IgG2, 0.345 for IgG3, and 0.448 for IgG4
      before treatment. After treatment, the correlation coefficient was 0.376 for IgG,
      0.522 for IgG1, 0.314 for IgG2, 0.582 for IgG3 and 0.503 for IgG4. Spearman's
      rank correlation coefficient was 0.801 for IgG1, 0.66 for IgG2, 0.575 for IgG3
      and 0.463 for IgG4 between the ELISA scores of IgG subclasses and the disease
      severity score variation. The ELISA scores of IgG subclasses in patients with
      mucosal involvement were higher than those without. Survival analysis showed that
      sex, IgG1 and IgG4 were the independent predictors for BP. In conclusion, the
      serum levels of IgG1 and IgG4 targeting BP180NC16A were paralleled with disease
      severity in BP patients. IgG1 and IgG4 and sex were the independent prognostic
      factors for an early prognosis of BP. 

PMID- 26300467
TI  - The Development of the Scale of Protective Factors: Resilience in a Violent
      Trauma Sample.
AB  - This research developed the Scale of Protective Factors (SPF-24) to measure
      protective factors contributing to resilience. We investigated the factor
      structure of 35 items. After exploratory factor analysis, we subjected 25 items
      representing 2 social-interpersonal and 2 cognitive-individual factors to
      confirmatory factor analysis. The sample consisted of 942 college students from 3
      studies and 2 institutions. To examine the diagnostic function of the SPF, we
      used clinical criteria to identify a subsample of participants who had
      experienced violent trauma and scored low, moderate, or high on an established
      resilience scale. Results showed that the low-resilient group scored
      significantly lower on all subscales of the SPF with marked differences in
      prioritizing/planning behavior. Implications for the research and clinical
      settings are discussed. 

PMID- 26300466
TI  - Re-thinking HIV-Related Stigma in Health Care Settings: A Qualitative Study.
AB  - People living with HIV (PLWH) continue to endure stigma and discrimination in the
      context of health care. This paper presents the findings of a qualitative study
      designed to (a) describe stigmatizing and discriminatory practices in health care
      settings, and (b) explore both symbolic and structural stigma from the
      perspectives of PLWH. For the purpose of this qualitative study, 21 semi
      structured in-depth interviews were conducted in the province of Quebec, Canada.
      The data were analyzed following the principles of thematic analysis. During
      analysis, three themes were identified, and relations between these themes were
      delineated to reflect the experiences of participants. The findings suggest that
      HIV-related stigma in health care settings is episodic in nature. The findings
      also suggest that HIV-related stigma is experienced through interactions with
      health care providers (symbolic stigma) and, finally, that it is applied
      systematically to manage risk in the context of health care (structural stigma). 

PMID- 26300468
TI  - Learning to (dis)like: The effect of evaluative conditioning with tastes and
      faces on odor valence assessed by implicit and explicit measurements.
AB  - Evaluative conditioning may be an important mechanism for learning food
      preferences and aversions; however, in both real life and experimental settings
      it has not been consistently successful. The current study aimed to gain more
      insight into which underlying factors may contribute to a successful outcome of
      olfactory evaluative conditioning. Two groups of 18 participants came in on three
      consecutive days, and were repeatedly exposed to four novel, neutral odors (CS)
      coupled to varying disliked, neutral, liked, or no stimuli (taste and/or
      pictures, US), following a 50% reinforcement schedule, leading to 40 odor
      presentations per session. Liking ratings, as well as changes in the autonomic
      nervous system were assessed before, during and after conditioning. We were able
      to induce negative, but not positive, affective changes by pairing neutral odors
      with tastes and pictures differing in valence. Negative as well as multimodal
      stimuli appear to be more potent US, since they may be considered more salient.
      Lastly, results of the current study imply that heart rate is responsive to
      changes in valence of olfactory stimuli, and perhaps even more sensitive than
      explicit ratings of liking. 

PMID- 26300469
TI  - Evidence of D2 receptor expression in the nucleus incertus of the rat.
AB  - The nucleus incertus (NI), located in the caudal brainstem, mainly consists of
      GABAergic neurons with widespread projections across the brain. It is the chief
      source of relaxin-3 in the mammalian brain and densely expresses corticotropin
      releasing factor type 1 (CRF1) receptors. Several other neurotransmitters,
      peptides and receptors are reportedly expressed in the NI. In the present
      investigation, we show the expression of dopamine type-2 (D2) receptors in the NI
      by reverse transcriptase-polymerase chain reaction (RT-PCR), western blotting
      (WB) and immunofluorescence (IF). RT-PCR did not show expression of D3 receptors.
      D2 receptor short isoform (D2S)-like, relaxin-3, CRF1/2 receptor and NeuN
      immunoreactivity were co-expressed in the cells of the NI. Behavioural effects of
      D2 receptor activation by intra-NI infusion of quinpirole (a D2/D3 agonist) were
      evaluated. Hypolocomotion was observed in home cage monitoring system (LABORAS)
      and novel environment-induced suppression of feeding behavioural paradigms. Thus
      the D2 receptors expressed in the NI are likely to play a role in locomotion.
      Based on its strong bidirectional connections to the median raphe and
      interpeduncular nuclei, the NI was predicted to play a role in modulating
      behavioural activity and the present results lend support to this hypothesis.
      This is the first evidence of expression of a catecholamine receptor, D2-like
      immunoreactivity, in the NI. 

PMID- 26300470
TI  - Alpha-linolenic acid suppresses dopaminergic neurodegeneration induced by 6-OHDA
      in C. elegans.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disorder
      characterized by the specific and massive loss of dopamine (DA) containing
      neurons in the substantia nigra pars compacta (SNpc) and aggregation of protein
      alpha-synuclein. There are a few animal studies, which indirectly implicate the
      neuroprotective action of omega-3 polyunsaturated fatty acids in
      neurodegenerative diseases. In this study, we exposed Caenorhabditis elegans
      (both wild type N2, and transgenic strain, UA44) to 6-hydroxydopamine (6-OHDA,
      the model neurotoxicant) and evaluated the extent of protection offered by alpha
      linolenic acid (ALA). Larval stage worms (L1/L2) of N2 and transgenic strains
      were exposed to 6-OHDA (25 mM) with or without ALA (10, 50 and 100 MUM) for 48 h
      at 20  degrees C. After 48 h, while the N2 worms were assessed for their
      responses in terms of locomotion, pharyngeal pumping, lifespan and AChE activity,
      the transgenic worms were monitored for dopaminergic neuronal degeneration. Worms
      exposed to 6-OHDA exhibited a significant reduction (48%) in the locomotion rate.
      Interestingly, supplementation with ALA increased the locomotion rate in 6-OHDA
      treated worms. A marked decrease (45%) in thrashing was evident in worms exposed
      to 6-OHDA while thrashing was slightly improved in worms co-exposed to 6-OHDA and
      higher concentrations of ALA. Interestingly, worms co-exposed to 6-OHDA with ALA
      (100 MUM) exhibited a significant increase in thrashing (66 +/- 1.80
      thrashes/30s). The pharyngeal pumping rate declined significantly in the case of
      worms exposed to 6-OHDA (35%). However, the worms co-treated with ALA exhibited
      significant recovery in pharyngeal pumping. The mean survival for the control
      worms was 26 days, while the worms exposed to 6-OHDA, showed a marked reduction
      in survival (21 days). Worms co-exposed to 6-OHDA and ALA showed a concentration
      dependent increase in lifespan compared to those exposed to 6-OHDA alone (23, 25
      and 26 days respectively). Transgenic worms treated with 6-OHDA showed
      significant loss of processes of CEP and ADE neurons as evident from visibly
      marked reduction in GFP expression. Worms co-exposed to 6-OHDA and ALA showed
      visibly significant reduction in neuronal degeneration in both CEP and ADE.
      However, worms exposed to 6-OHDA together with ALA showed increased GFP
      expression within processes of CEP and ADE neurons. Overall, our results
      demonstrate that ALA significantly suppresses the dopaminergic neurodegeneration
      and movement disorder induced by 6-OHDA in C. elegans.

PMID- 26300471
TI  - Social factors and readmission after inpatient detoxification in older alcohol
      dependent patients.
AB  - BACKGROUND AND OBJECTIVES: Alcohol dependence is often a chronic relapsing
      disorder with frequent admissions to inpatient facilities. This study in older
      alcohol-dependent inpatients investigates the role of social factors in
      readmissions after inpatient detoxification. METHODS: In a prospective study, 132
      older alcohol-dependent patients admitted to inpatient detoxification (mean age
      63.4, SD = 6.6, 39.4% women) were interviewed with the European version of the
      Addiction Severity Index (Europ-ASI). Readmission to inpatient treatment was
      monitored up to 1 year after discharge. The effect of social factors on
      readmission, the number of readmissions and the time to first readmission was
      established using group comparisons, Poisson regression analysis, and Cox'
      proportional hazards regression analysis, respectively. RESULTS: Sixty-seven
      (50.8%) of the 132 patients were readmitted within 1 year. In this group, the
      median number of readmissions was 2 (IQR = 2, range 1-6) and the median time to
      first readmission was 88 days (IQR = 116, range 3-356). In a multivariate
      analysis, spending most leisure time alone predicted fewer readmissions. None of
      the other social factors predicted readmission, number of readmissions or time to
      first readmission. DISCUSSION AND CONCLUSIONS: Rehospitalization of older alcohol
      dependent patients after detoxification is very common, and generally not
      predicted by social factors. Only spending most leisure time alone may play a
      role. SCIENTIFIC SIGNIFICANCE: This study shows that most social factors are
      unexpectedly-not associated with rehospitalization of older alcohol-dependent
      patients after detoxification. "Spending leisure time alone" warrants further
      study as a potentially modifiable predictor.

PMID- 26300472
TI  - Activation of Single-Component Nickel(II) Polyethylene Catalysts via Phase
      Transfer of Fluorous Phosphine Ligands.
AB  - The nickel salicylaldiminato phosphine complexes [1,2,3-C6H3(9
      anthracenyl)O(CH?N(2,6-C6H3(iPr)2)]Ni(Me)[P(4-C6H4R)3] (4; R = a, (CH2)2Rf8; b,
      (CH2)3Rf8; c, H (Rf8 = (CF2)7CF3)) are prepared from the corresponding phosphines
      3a-c and nickel NCMe adduct (46-68%). These are applied as catalysts for ethylene
      polymerization in toluene and fluorous/toluene liquid/liquid biphasic mixtures.
      Under the latter conditions, the fluorous phosphines 3a,b that must dissociate to
      generate the active catalyst migrate to the fluorous phase (partition
      coefficients 97.5:2.5 and 66.6:33.4 vs <0.5:>99.5 for 4a,b). Catalysts 4a,b show
      marked accelerations under biphasic conditions, but 4c (which has a lipophilic
      phosphine ligand) does not. Under all conditions, 4a,b are faster catalysts than
      the Ni(Ph)(PPh3) analogue, a previously reported benchmark. 

PMID- 26300474
TI  - Melanocortin receptor agonist ACTH 1-39 protects rat forebrain neurons from
      apoptotic, excitotoxic and inflammation-related damage.
AB  - Patients with relapsing-remitting multiple sclerosis (RRMS) are commonly treated
      with high doses of intravenous corticosteroids (CS). ACTH 1-39, a member of the
      melanocortin family, stimulates production of CS by the adrenals, but
      melanocortin receptors are also found in the central nervous system (CNS) and on
      immune cells. ACTH is produced within the CNS and may have direct protective
      effects on glia and neurons independent of CS. We previously reported that ACTH 1
      39 protected oligodendroglia (OL) and their progenitors (OPC) from a panel of
      excitotoxic and inflammation-related agents. Neurons are the most vulnerable
      cells in the CNS. They are terminally differentiated, and sensitive to
      inflammatory and excitotoxic insults. For potential therapeutic protection of
      gray matter, it is important to investigate the direct effects of ACTH on
      neurons. Cultures highly enriched in neurons were isolated from 2-3 day old rat
      brain. After 4-7 days in culture, the neurons were treated for 24h with selected
      toxic agents with or without ACTH 1-39. ACTH 1-39 protected neurons from death
      induced by staurosporine, glutamate, NMDA, AMPA, kainate, quinolinic acid,
      reactive oxygen species and, to a modest extent, from rapidly released NO, but
      did not protect against kynurenic acid or slowly released nitric oxide. Our
      results show that ACTH 1-39 protects neurons in vitro from several apoptotic,
      excitotoxic and inflammation-related insults.

PMID- 26300473
TI  - CAMKII-conditional deletion of histone deacetylase 2 potentiates acute
      methamphetamine-induced expression of immediate early genes in the mouse nucleus
      accumbens.
AB  - Methamphetamine (METH) produces increases in the expression of immediate early
      genes (IEGs) and of histone deacetylase 2 (HDAC2) in the rat nucleus accumbens
      (NAc). Here, we tested whether HDAC2 deletion influenced the effects of METH on
      IEG expression in the NAc. Microarray analyses showed no baseline differences in
      IEG expression between wild-type (WT) and HDAC2 knockout (KO) mice. Quantitative
      PCR analysis shows that an acute METH injection produced time-dependent increases
      in mRNA levels of several IEGs in both genotypes. Interestingly, HDAC2KO mice
      displayed greater METH-induced increases in Egr1 and Egr2 mRNA levels measured at
      one hour post-injection. The levels of Fosb, Fra2, Egr1, and Egr3 mRNAs stayed
      elevated in the HDAC2KO mice 2 hours after the METH injection whereas these mRNAs
      had normalized in the WT mice. In WT mice, METH caused increased HDAC2
      recruitment to the promoters some IEGs at 2 hours post injection. METH-induced
      prolonged increases in Fosb, Fra2, Egr1, and Egr3 mRNA levels in HDAC2KO mice
      were associated with increased enrichment of phosphorylated CREB (pCREB) on the
      promoters of these genes. Based on our observations, we hypothesize that HDAC2
      may regulate the expression of these genes, in part, by prolonging the actions of
      pCREB in the mouse NAc. 

PMID- 26300475
TI  - Protective effects of Ndfip1 on MPP(+)-induced apoptosis in MES23.5 cells and its
      underlying mechanisms.
AB  - Apoptosis has been implicated as one of the important mechanisms involved in the
      degeneration of dopaminergic neurons in Parkinson's disease (PD). Increasing
      evidence suggests that Ndfip1 is a neuroprotective protein, and Ndfip1-mediated
      protein ubiquitination might be a possible survival strategy in neuronal injury.
      The aim of the present study is to investigate the neuroprotective effect of
      Ndfip1 on 1-methyl-4-phenylpyridinium (MPP(+))-treated MES23.5 cells and the
      underlying mechanisms. Results showed that overexpression of Ndfip1 could
      significantly attenuate MPP(+)-induced cell loss and nuclear condensation.
      Further experiments demonstrated that Ndfip1 could increase Bcl-2/Bax ratio,
      suppress cytochrome c release from the mitochondria to cytoplasm and decrease
      caspase-3 activation induced by MPP(+). These results suggested that Ndfip1
      protected MES23.5 cells against MPP(+) by its anti-apoptotic effect. In addition,
      we found that Ndfip1 overexpression could decrease the protein level of dopamine
      transporter (DAT). In parallel, proteasome inhibitor MG132 could markedly reverse
      Ndfip1-induced degradation of DAT. These data suggest that Ndfip1 exerts its
      inhibitory effect on DAT by modulating DAT degradation, in which ubiquitin
      proteasome system activation might be involved. Collectively, our study indicated
      that the ability to decrease the DAT of Ndfip1 might be one of the mechanisms
      underlying its protective effect on MPP(+)-induced cell damage in MES23.5 cells. 

PMID- 26300476
TI  - Climate-induced warming imposes a threat to north European spring ecosystems.
AB  - Interest in climate change effects on groundwater has increased dramatically
      during the last decade. The mechanisms of climate-related groundwater depletion
      have been thoroughly reviewed, but the influence of global warming on groundwater
      dependent ecosystems (GDEs) remains poorly known. Here we report long-term water
      temperature trends in 66 northern European cold-water springs. A vast majority of
      the springs (82%) exhibited a significant increase in water temperature during
      1968-2012. Mean spring water temperatures were closely related to regional air
      temperature and global radiative forcing of the corresponding year. Based on
      three alternative climate scenarios representing low (RCP2.6), intermediate
      (RCP6) and high-emission scenarios (RCP8.5), we estimate that increase in mean
      spring water temperature in the region is likely to range from 0.67  degrees C
      (RCP2.6) to 5.94  degrees C (RCP8.5) by 2086. According to the worst-case
      scenario, water temperature of these originally cold-water ecosystems (regional
      mean in the late 1970s: 4.7  degrees C) may exceed 12  degrees C by the end of
      this century. We used bryophyte and macroinvertebrate species data from Finnish
      springs and spring-fed streams to assess ecological impacts of the predicted
      warming. An increase in spring water temperature by several degrees will likely
      have substantial biodiversity impacts, causing regional extinction of native,
      cold-stenothermal spring specialists, whereas species diversity of headwater
      generalists is likely to increase. Even a slight (by 1  degrees C) increase in
      water temperature may eliminate endemic spring species, thus altering bryophyte
      and macroinvertebrate assemblages of spring-fed streams. Climate change-induced
      warming of northern regions may thus alter species composition of the spring
      biota and cause regional homogenization of biodiversity in headwater ecosystems. 

PMID- 26300478
TI  - Decontamination of poultry feed from ochratoxin A by UV and sunlight radiations.
AB  - BACKGROUND: Mycotoxin-contaminated feed is very dangerous for the growth and even
      life of poultry. The objective of the current study was to investigate the
      efficacy of ultra-violet irradiation for decontamination of ochratoxin A (OTA) in
      spiked and naturally contaminated poultry feed samples. Spiked and naturally
      contaminated feed samples were irradiated with ultra-violet light (UV) at
      distance of 25 cm over the feed samples. In vitro, the effect of UV intensity
      (0.1 mW cm(-2) at 254 nm UV-C) on different types of poultry feeds contaminated
      with OTA was evaluated. The same samples were also irradiated with sunlight and
      analysed for OTA by an indirect enzyme linked immunosorbent assay method.
      RESULTS: Poultry feed samples containing 500 ug kg(-1) were 100% decontaminated
      in 180 min with UV radiation while OTA was decreased to 70-95 ug kg(-1) using the
      same poultry feed samples after 8 h sunlight irradiation. Therefore, UV light was
      found to be more effective. Only 1 h of UV irradiation was found to be sufficient
      to bring the OTA level to the maximum regulatory limit suggested for poultry
      feeds (100 ug kg(-1) ), while 8 h were needed to obtain this level using sunlight
      radiations. CONCLUSION: The proposed approach is a viable option to reduce the
      level of OTA in contaminated poultry feeds. (c) 2015 Society of Chemical
      Industry.

PMID- 26300477
TI  - Audit of practice in sudden unexpected death in epilepsy (SUDEP) post mortems and
      neuropathological findings.
AB  - AIMS: Sudden unexpected death in epilepsy (SUDEP) is one of the leading causes of
      death in people with epilepsy. For classification of definite SUDEP, a post
      mortem (PM), including anatomical and toxicological examination, is mandatory to
      exclude other causes of death. We audited PM practice as well as the value of
      brain examination in SUDEP. METHODS: We reviewed 145 PM reports in SUDEP cases
      from four UK neuropathology centres. Data were extracted for clinical epilepsy
      details, circumstances of death and neuropathological findings. RESULTS:
      Macroscopic brain abnormalities were identified in 52% of cases. Mild brain
      swelling was present in 28%, and microscopic pathologies relevant to cause or
      effect of seizures were seen in 89%. Examination based on whole fixed brains
      (76.6% of all PMs), and systematic regional sampling was associated with higher
      detection rates of underlying pathology (P < 0.01). Information was more
      frequently recorded regarding circumstances of death and body position/location
      than clinical epilepsy history and investigations. CONCLUSION: Our findings
      support the contribution of examination of the whole fixed brain in SUDEP, with
      high rates of detection of relevant pathology. Availability of full clinical
      epilepsy-related information at the time of PM could potentially further improve
      detection through targeted tissue sampling. Apart from confirmation of SUDEP,
      complete neuropathological examination contributes to evaluation of risk factors
      as well as helping to direct future research into underlying causes.

PMID- 26300479
TI  - Two-step dispersive-solid phase extraction strategy for pesticide multiresidue
      analysis in a chlorophyll-containing matrix by gas chromatography-tandem mass
      spectrometry.
AB  - Two-step dispersive-solid phase extraction strategy for the cleanup of QuEChERS
      extracts in multiresidue analysis of current-use pesticides in a chlorophyll
      containing matrix was evaluated and is reported for the first time. The proposed
      approach combines two sequential steps of dispersive-solid phase extraction (d
      SPE) to reduce matrix co-extractives. In the first step, primary secondary amine
      (PSA) together with a new type of sorbent, known as ChloroFiltr, was employed.
      This was followed by a second step of d-SPE using octadecyl (C18) and graphitized
      carbon black (GCB). Also, new zirconium dioxide-based sorbents (Z-Sep+ and Z
      Sep/C18) were evaluated but the use of GCB/C18 provided the highest pesticide
      coverage with recoveries in the range of 70-120% from spiked green soybean
      samples. The final extracts were analyzed by gas chromatography coupled to tandem
      mass spectrometry (GC-MS/MS). The overall recoveries at three spiking levels of
      0.01, 0.05 and 0.2 mg kg(-1) were 96+/-15%, 93+/-13% and 92+/-13% with relative
      standard deviations of 10+/-7%, 9+/-5%, and 11+/-5%, respectively. The proposed
      method provided matrix effect <20% for 77% of the target compounds, which may be
      considered as negligible because such variability is closed to the accepted
      repeatability. For the rest of 8 and 15% of the compounds, the matrix effect was
      20-30% and >30%, respectively. The developed method was successfully applied to
      study dissipation patterns of pesticides applied to soybean in experimental plot
      trials, thus contributing to establish safe and proper use of pesticides by
      extension of authorization on minor crops in Poland.

PMID- 26300480
TI  - Simultaneous separation of acidic and basic proteins using gemini pyrrolidinium
      surfactants and hexafluoroisopropanol as dynamic coating additives in capillary
      electrophoresis.
AB  - The separation of acidic and basic proteins using CE has been limited in part due
      to the adsorption of proteins onto the capillary wall. In this work, the
      efficient control of EOF and the simultaneous separation of acidic and basic
      proteins are achieved by use of C18-4-C18PB as a dynamic coating additive, which
      is a representative surfactant for 1,1'-(butane-1,s-alkyl)bis(1
      alkylpyrrolidinium) bromide (Cn-4-CnPB, n=10, 12, 14, 16 and 18). C18-4-C18PB
      exhibits a powerful capability in the reversal of EOF, and a low concentration
      even less than 0.001 mM is sufficient to reverse EOF at the tested pH values (3.0
      9.0). Baseline separation of eight proteins with sharp peaks and high
      efficiencies (54,000-297,000 plates/m) is obtained with 30 mM NaH2PO4 buffer (pH
      5.0) containing 4 mM C18-4-C18PB. At the same buffer condition, the Cn-4-CnPB
      with shorter alkyl chain (n=10, 12, 14, 16) cannot achieve the same effective
      protein separation as C18-4-C18PB. However, the combined use of small amounts
      (<=0.5%, v/v) of hexafluoroisopropanol (HFIP) and Cn-4-CnPB (n=10, 12, 14, 16) as
      additives can completely separate all eight proteins with high efficiencies of
      81,000-318,000 plates/m. The RSDs of migration time are less than 0.80% and 5.84%
      for run-to-run and day-to-day assays (n=5), respectively, and the protein
      recoveries are larger than 90.15%. To the best of our knowledge, this is the
      first report on the simultaneous separation of acidic and basic proteins using Cn
      4-CnPB surfactants or Cn-4-CnPB surfactants combined with HFIP as dynamic coating
      additives.

PMID- 26300482
TI  - [Lobar torsion after lobectomy].

PMID- 26300481
TI  - A one-step preparation method of monolithic enzyme reactor for highly efficient
      sample preparation coupled to mass spectrometry-based proteomics studies.
AB  - Mass spectrometry (MS) coupled to sample preparation and separation techniques
      has become a primary tool for proteomics studies. However, due to sample
      complexity, it is often challenging to achieve fast and efficient sample
      preparation prior to MS analysis. In recent decades, monolithic materials have
      been developed not only as chromatographic media, but also as efficient solid
      supports for immobilizing multiple types of affinity reagents. Herein, the N
      acryloxysuccinimide-co-acrylamide-co-N,N'-methylenebisacrylamide (NAS-AAm-Bis)
      monolith was fabricated within silanized 200 MUm i.d. fused-silica capillaries
      and was used as an immobilized enzyme reactor (IMER). The column was conjugated
      with trypsin/Lys-C and Lys-N enzymes to allow enzymatic digestions to occur while
      protein mixture was loaded onto the IMER column followed by MS-based proteomics
      analysis. Similar MS signal and protein sequence coverage were observed using
      protein standard bovine serum albumin (BSA) compared to in-solution digestion.
      Furthermore, mouse serum, yeast, and human cell lysate samples were also
      subjected to enzymatic digestion by both IMER (in seconds to minutes) and
      conventional in solution digestion (overnight) for comparison in large-scale
      proteomics studies. Comparable protein identification results obtained by the two
      methods highlighted the potential of employing NAS-based IMER column for fast and
      highly efficient sample preparation for MS analysis in proteomics studies.

PMID- 26300483
TI  - Toll-like receptor 5 deficiency attenuates interstitial cardiac fibrosis and
      dysfunction induced by pressure overload by inhibiting inflammation and the
      endothelial-mesenchymal transition.
AB  - Vascular dysfunction, characterized by the endothelial-to-mesenchymal transition
      (EndMT), contributes to the development of cardiac fibrosis induced by pressure
      overload. Toll-like receptor (TLR)5 is a member of the TLR family that is
      expressed on not only immune cells but also nonimmune cells including
      cardiomyocytes and vascular endothelial cells. The level of TLR5 expression on
      endothelial cells is low under normal circumstances but is increased in response
      to stimuli such as pressure overload. The aim of this study was to investigate
      the importance of TLR5 in cardiac endothelial dysfunction during the development
      of cardiac fibrosis induced by pressure overload. Global TLR5-deficient mice and
      wild-type littermates underwent aortic banding (AB) for 8weeks to induce cardiac
      fibrosis, hypertrophy and dysfunction. The deficiency of TLR5 in this model
      exerted no basal effects but attenuated the cardiac fibrosis, hypertrophy and
      dysfunction induced by pressure overload. AB-induced endothelial TLR5 activation
      enhanced the development of cardiac fibrosis independent of cardiomyocyte
      hypertrophy and triggered left ventricular dysfunction. TLR5-deficient mice also
      exhibited ameliorated myocardial pro-inflammatory cytokine expression and
      macrophage infiltration and inhibited the EndMT, all of which contribute to the
      development of cardiac fibrosis. These findings suggest that TLR5 triggers
      inflammatory responses and promotes the EndMT, which may be an important
      mechanism underlying the promotion of cardiac fibrosis and left ventricular
      dysfunction during pressure overload. 

PMID- 26300484
TI  - Blockade of exosome generation with GW4869 dampens the sepsis-induced
      inflammation and cardiac dysfunction.
AB  - Sepsis is an infection-induced severe inflammatory disorder that leads to
      multiple organ failure. Amongst organs affected, myocardial depression is
      believed to be a major contributor to septic death. While it has been identified
      that large amounts of circulating pro-inflammatory cytokines are culprit for
      triggering cardiac dysfunction in sepsis, the underlying mechanisms remain
      obscure. Additionally, recent studies have shown that exosomes released from
      bacteria-infected macrophages are pro-inflammatory. Hence, we examined in this
      study whether blocking the generation of exosomes would be protective against
      sepsis-induced inflammatory response and cardiac dysfunction. To this end, we pre
      treated RAW264.7 macrophages with GW4869, an inhibitor of exosome
      biogenesis/release, followed by endotoxin (LPS) challenge. In vivo, we injected
      wild-type (WT) mice with GW4869 for 1h prior to endotoxin treatment or cecal
      ligation/puncture (CLP) surgery. We observed that pre-treatment with GW4869
      significantly impaired release of both exosomes and pro-inflammatory cytokines
      (TNF-alpha, IL-1beta, IL-6) in RAW264.7 macrophages. At 12h after LPS treatment
      or CLP surgery, WT mice pre-treated with GW4869 displayed lower amounts of
      exosomes and pro-inflammatory cytokines in the serum than control PBS-injected
      mice. Accordingly, GW4869 treatment diminished the sepsis-induced cardiac
      inflammation, attenuated myocardial depression and prolonged survival. Together,
      our findings indicate that blockade of exosome generation in sepsis dampens the
      sepsis-triggered inflammatory response and thereby, improves cardiac function and
      survival. 

PMID- 26300485
TI  - HDAC6 inhibition induces mitochondrial fusion, autophagic flux and reduces
      diffuse mutant huntingtin in striatal neurons.
AB  - Striatal neurons are vulnerable to Huntington's disease (HD). Decreased levels of
      acetylated alpha-tubulin and impaired mitochondrial dynamics, such as reduced
      motility and excessive fission, are associated with HD; however, it remains
      unclear whether and how these factors might contribute to the preferential
      degeneration of striatal neurons. Inhibition of the alpha-tubulin deacetylase
      HDAC6 has been proposed as a therapeutic strategy for HD, but remains
      controversial - studies in neurons show improved intracellular transport, whereas
      studies in cell-lines suggest it may impair autophagosome-lysosome fusion, and
      reduce clearance of mutant huntingtin (mHtt) and damaged mitochondria
      (mitophagy). Using primary cultures of rat striatal and cortical neurons, we show
      that mitochondria are intrinsically less motile and more balanced towards fission
      in striatal than in cortical neurons. Pharmacological inhibition of the HDAC6
      deacetylase activity with tubastatin A (TBA) increased acetylated alpha-tubulin
      levels, and induced mitochondrial motility and fusion in striatal neurons to
      levels observed in cortical neurons. Importantly, TBA did not block neuronal
      autophagosome-lysosome fusion, and did not change mitochondrial DNA levels,
      suggesting no impairment in autophagy or mitochondrial clearance. Instead, TBA
      increased autophagic flux and reduced diffuse mHtt in striatal neurons, possibly
      by promoting transport of initiation factors to sites of autophagosomal
      biogenesis. This study identifies the pharmacological inhibition of HDAC6
      deacetylase activity as a potential strategy to reduce the vulnerability of
      striatal neurons to HD. 

PMID- 26300487
TI  - Downregulation of STIM2 improves neuronal survival after traumatic brain injury
      by alleviating calcium overload and mitochondrial dysfunction.
AB  - Although store-operated calcium entry (SOCE) has been implicated in several
      neurological disorders, the exact mechanism for its role in traumatic brain
      injury (TBI) has not been elucidated. In this study, we found that TBI
      upregulated the expression of a calcium sensor protein called stromal interactive
      molecule 2 (STIM2); however, the levels of its homologue, STIM1, were unaffected.
      Both STIM1 and STIM2 are crucial components of SOCE, both in vivo and in vitro.
      Using shRNA, we discovered that downregulation of STIM2, but not STIM1,
      significantly improved neuronal survival in both an in vitro and in vivo model of
      TBI, decreasing neuronal apoptosis, and preserving neurological function. This
      neuroprotection was associated with alleviating TBI-induced calcium overload and
      preserving mitochondrial function. Additionally, downregulation of STIM2 not only
      inhibited Ca(2+) release from the endoplasmic reticulum (ER), but also reduced
      SOCE-mediated Ca(2+) influx, decreased mitochondrial Ca(2+), restored
      mitochondrial morphology and improved mitochondrial function, including MMP
      maintenance, ROS production and ATP synthesis. These results indicate that
      inhibition of STIM2 can protect neurons from TBI by inhibiting calcium overload
      and preserving mitochondrial function. This suggests that STIM2 might be an
      effective interventional target for TBI. 

PMID- 26300486
TI  - Fructose consumption reduces hippocampal synaptic plasticity underlying cognitive
      performance.
AB  - Metabolic syndrome (MetS) is a global epidemic, which involves a spectrum of
      metabolic disorders comprising diabetes and obesity. The impact of MetS on the
      brain is becoming to be a concern, however, the poor understanding of mechanisms
      involved has limited the development of therapeutic strategies. We induced a MetS
      like condition by exposing mice to fructose feeding for 7weeks. There was a
      dramatic deterioration in the capacity of the hippocampus to sustain synaptic
      plasticity in the forms of long-term potentiation (LTP) and long-term depression
      (LTD). Mice exposed to fructose showed a reduction in the number of contact zones
      and the size of postsynaptic densities (PSDs) in the hippocampus, as well as a
      decrease in hippocampal neurogenesis. There was an increase in lipid peroxidation
      likely associated with a deficiency in plasma membrane excitability. Consistent
      with an overall hippocampal dysfunction, there was a subsequent decrease in
      hippocampal dependent learning and memory performance, i.e., spatial learning and
      episodic memory. Most of the pathological sequel of MetS in the brain was
      reversed three month after discontinue fructose feeding. These results are novel
      to show that MetS triggers a cascade of molecular events, which disrupt
      hippocampal functional plasticity, and specific aspects of learning and memory
      function. The overall information raises concerns about the risk imposed by
      excessive fructose consumption on the pathology of neurological disorders. 

PMID- 26300488
TI  - Baicalin alleviates diabetes-associated cognitive deficits via modulation of
      mitogen-activated protein kinase signaling, brain-derived neurotrophic factor and
      apoptosis.
AB  - Baicalin is an important active component of the medicinal herb Scutellaria
      baicalensis Georgi and has shown a variety of pharmacological actions. The
      present study aimed to evaluate the neuroprotective effects of baicalin against
      diabetes-associated cognitive deficits (DACD) in rats and to elucidate the
      potential molecular mechanisms of action. A rat model of diabetes mellitus was
      prepared by intraperitoneal injection of streptozotocin. After the successful
      establishment of the diabetic rat model, baicalin (50, 100 and 200 mg/kg) or
      vehicle was administrated for seven weeks. Learning and memory function were
      assessed using the Morris water maze test. At the end of the experiment, the
      activities of acetylcholinesterase (AChE) and choline acetylase (ChAT) were
      determined using commercial kits. Furthermore, the expression of proteins
      involved in mitogen-activated protein kinase (MAPK) cascades [extracellular
      signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38], brain
      derived neurotrophic factor (BDNF) and apoptosis-associated proteins [caspase-3,
      B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax)] were detected by
      western blot analysis. Caspase-3 activity was also analyzed using a commercial
      kit. The results demonstrated that diabetic rats exhibited decreases in body
      weight, decreases in the percentage of time spent in the target quadrant and the
      number of times of crossing the platform in the water maze test, as well as
      decreases in neuronal survival, ChAT, phosphorylated (p)ERK, BDNF and Bcl-2.
      Furthermore, diabetic rats showed increases in escape latency and mean path
      length in the water maze test, increases in the levels of hippocampal AChE, p
      JNK, p-p38, caspase-3 and Bax as well as plasma glucose. However, in diabetic
      rats treated with baicalin, all of the abovementioned observations were obviously
      reversed. The findings suggested that baicalin exerts neuroprotective effects
      against DACD via modulation of MAPK cascades, BDNF and apoptosis.

PMID- 26300489
TI  - Workplace health promotion and labour market performance of employees.
AB  - This paper investigates the average effects of firm-provided workplace health
      promotion measures on labour market outcomes of the firms' employees. Exploiting
      linked employer-employee panel data that consist of rich survey-based and
      administrative information on firms, workers and regions, we apply a flexible
      propensity score matching approach that controls for selection on observables and
      time-constant unobserved factors. While the effects of analysing sickness
      absenteeism appear to be rather limited, our results suggest that health
      circles/courses increase tenure and job stability across various age groups. A
      key finding is that health circles/courses strengthen the labour force attachment
      of elderly employees (51-60), implying potential cost savings for public transfer
      schemes such as unemployment insurance or early retirement schemes. 

PMID- 26300490
TI  - A Direct Aqueous Derivatization GSMS Method for Determining Benzoylecgonine
      Concentrations in Human Urine.
AB  - A sensitive and reliable method for extraction and quantification of
      benzoylecgonine (BZE) and cocaine (COC) in urine is presented. Propyl
      chloroformate was used as derivatizing agent, and it was directly added to the
      urine sample: the propyl derivative and COC were then recovered by liquid-liquid
      extraction procedure. Gas chromatography-mass spectrometry was used to detect the
      analytes in selected ion monitoring mode. The method proved to be precise for BZE
      and COC both in term of intraday and interday analysis, with a coefficient of
      variation (CV)<6%. Limits of detection (LOD) were 2.7 ng/mL for BZE and 1.4 ng/mL
      for COC. The calibration curve showed a linear relationship for BZE and COC
      (r2>0.999 and >0.997, respectively) within the range investigated. The method,
      applied to thirty authentic samples, showed to be very simple, fast, and
      reliable, so it can be easily applied in routine analysis for the quantification
      of BZE and COC in urine samples.

PMID- 26300492
TI  - Stabilization of MCRS1 by BAP1 prevents chromosome instability in renal cell
      carcinoma.
AB  - Characterization of the exome and genome of carcinoma (ccRCC) by next-generation
      sequencing identified numerous genetic alternations. BRCA1-associated protein-1
      (BAP1) was identified as one of the most frequently mutated genes in ccRCC,
      suggesting that BAP1 is a potential key driver for ccRCC cancer initiation and
      progression. However, how BAP1 mutations contribute to ccRCC remains to be
      elucidated. BAP1 is a nuclear de-ubiquitinating enzyme and cleaves the ubiquitin
      chain from the substrates. Here, we identified MCRS1 as a bona fide substrate for
      BAP1. MCRS1 is a component of the centrosome proteins, and plays an essential
      role in spindle assembly. BAP1 binds to MCRS1 and stabilizes MCRS1 by de
      ubiquitination. BAP1 contributes to chromosome stability partially via MCRS1. A
      positive correlation was identified between BAP1 and MCRS1 expression in ccRCC
      tissues. Both BAP1 loss and MCRS1 down-regulation in ccRCC were associated with
      adverse clinicopathological features. This study revealed a novel mechanism for
      BAP1 involved in MCRS1 stability regulation, and provided insight in
      understanding the relationship between BAP1 mutations and chromosome instability
      in ccRCC. 

PMID- 26300491
TI  - Genetics of melanocytic nevi.
AB  - Melanocytic nevi are a benign clonal proliferation of cells expressing the
      melanocytic phenotype, with heterogeneous clinical and molecular characteristics.
      In this review, we discuss the genetics of nevi by salient nevi subtypes:
      congenital melanocytic nevi, acquired melanocytic nevi, blue nevi, and Spitz
      nevi. While the molecular etiology of nevi has been less thoroughly studied than
      melanoma, it is clear that nevi and melanoma share common driver mutations.
      Acquired melanocytic nevi harbor oncogenic mutations in BRAF, which is the
      predominant oncogene associated with melanoma. Congenital melanocytic nevi and
      blue nevi frequently harbor NRAS mutations and GNAQ mutations, respectively,
      while Spitz and atypical Spitz tumors often exhibit HRAS and kinase
      rearrangements. These initial 'driver' mutations are thought to trigger the
      establishment of benign nevi. After this initial phase of the cell proliferation,
      a senescence program is executed, causing termination of nevi growth. Only upon
      the emergence of additional tumorigenic alterations, which may provide an escape
      from oncogene-induced senescence, can malignant progression occur. Here, we
      review the current literature on the pathobiology and genetics of nevi in the
      hope that additional studies of nevi promise to inform our understanding of the
      transition from benign neoplasm to malignancy. 

PMID- 26300494
TI  - Transition-Metal-Free Synthesis of Ynones via Decarboxylative Alkynylation of
      alpha-Keto Acids under Mild Conditions.
AB  - A transition-metal-free synthetic method of various ynones via decarboxylative
      alkynylation of alpha-keto acids is described. The reaction is carried out under
      mild conditions and exhibits remarkable tolerance of functional groups. The
      mechanism of a radical process is proposed in the reaction. 

PMID- 26300493
TI  - NRF2/miR-140 signaling confers radioprotection to human lung fibroblasts.
AB  - Breast and lung cancer patients who are treated with radiotherapy often have
      severe side effects, including radiation-induced lung damage and secondary
      cancers. Activation of the NRF2 pathway is a well-known mechanism that protects
      cells against radiation induced oxidative stress, but its role in radiation
      induced lung damage is not well understood. Using human lung fibroblasts (HLFs)
      we found that ionizing radiation (IR) leads to BRCA1-dependent activation of NRF2
      through the inhibition of KEAP1 function, promoting the nuclear accumulation of
      NRF2, and activating critical radioprotective mechanisms. We discovered that NRF2
      directly binds to the miR-140 promoter and increases its expression in response
      to IR treatment. Gain and loss of function studies further showed the ability of
      miR-140 to regulate lung fibroblast self-renewal upon irradiation, a potential
      mechanism to contribute to the regulation of DNA repair. We verified our in vitro
      findings using primary lung fibroblast cultures from wild type and Nrf2 (KO)
      mice. Using these models we showed that IR induces overexpression of Brca1, Nrf2
      and miR-140 in lung tissue after irradiation. These data reveal a novel
      radioprotective mechanism in which IR promotes NRF2 nuclear translocation and
      subsequent activation of miR-140 transcription in HLFs. 

PMID- 26300495
TI  - Different adipose tissue depots: Metabolic implications and effects of surgical
      removal.
AB  - Increased adiposity has been associated to worse metabolic profile,
      cardiovascular disease, and mortality. There are two main adipose tissue depots
      in the body, subcutaneous and visceral adipose tissue, which differ in anatomical
      location. A large body of evidence has shown the metabolic activity of adipose
      tissue; lipectomy and/or liposuction therefore appear to be alternatives for
      improving metabolic profile through rapid loss of adipose tissue. However,
      surgical removal of adipose tissue may be detrimental for metabolism, because
      subcutaneous adipose tissue has not been associated to metabolic disorders such
      as insulin resistance and type 2 diabetes mellitus. In addition, animal studies
      have shown a compensatory growth of adipose tissue in response to lipectomy. This
      review summarizes the implications of obesity-induced metabolic dysfunction, its
      relationship with the different adipose tissue depots, and the effects of
      lipectomy on cardiometabolic risk factors. 

PMID- 26300496
TI  - Hyponatremic rhabdomyolysis in Addison's disease in a child with autoimmune
      polyglandular syndrome type 2.

PMID- 26300497
TI  - Childhood cerebral palsy and the use of positioning systems to control body
      posture: Current practices.
AB  - INTRODUCTION: One of the consequences of poor postural control in children with
      cerebral palsy is hip dislocation. This is due to the lack of weight-bearing in
      the sitting and standing positions. Orthotic aids can be used to prevent onset
      and/or progression. OBJECTIVE: The aim of this study is to analyse the
      effectiveness of positioning systems in achieving postural control in patients
      with cerebral palsy, and discuss these findings with an emphasis on what may be
      of interest in the field of neurology. DISCUSSION: We selected a total of 18
      articles on interventions in cerebral palsy addressing posture and maintenance of
      ideal postures to prevent deformities and related problems. The main therapeutic
      approaches employed combinations of botulinum toxin and orthoses, which reduced
      the incidence of hip dislocation although these results were not significant. On
      the other hand, using positioning systems in 3 different positions decreases use
      of botulinum toxin and surgery in children under 5 years old. The drawback is
      that these systems are very uncomfortable. CONCLUSION: Postural control systems
      helps control hip deformities in children with cerebral palsy. However, these
      systems must be used for prolonged periods of time before their effects can be
      observed.

PMID- 26300498
TI  - Superior vena cava syndrome as a complication of intravenous immunoglobulin
      treatment.

PMID- 26300499
TI  - Atypical pituitary adenomas: 10 years of experience in a reference centre in
      Portugal.
AB  - INTRODUCTION: Primary pituitary tumours are classified by the World Health
      Organization as typical adenoma, atypical adenoma, or carcinoma. Information on
      the incidence and prevalence of these pituitary tumours is limited, and these
      data in Portugal are scarce, obsolete, or non-existent. Our study evaluates
      pituitary adenomas (PA) in the population of Lisbon, and it aims to describe the
      prevalence of all subgroups in order to revise the incidence of the 'atypical'
      histological type and its correlation to tumour subtype, invasion, and
      recurrence. PATIENTS AND METHODS: A retrospective, descriptive analysis of
      patients with PA diagnosed between 2004 and 2013 was performed at Santa Maria
      University Hospital, a national reference centre. RESULTS: Of the 220 PA cases
      diagnosed, 28 (12.7%) fulfilled criteria for atypical lesions, and within that
      group, 23 were macroadenomas (82.1%) and 13 showed radiological evidence of
      invasion (46.4%). Ages ranged from 29 and 81 years (mean, 53.4 years). Eleven
      patients (39.3%) had functional tumours. Sixteen of the 28 patients (57.1%)
      experienced tumour recurrences; in the 100 adenomas monitored for more than 5
      years, the recurrence rate in atypical PA was 7 times higher than in typical PA.
      Immunohistochemically, 28.6% of the tumours stained positively for ACTH, 25% for
      gonadotrophins, and 17.9% for prolactin. The proliferation index (Ki67) ranged
      from 3% and 25% (mean, 6.4%). CONCLUSIONS: Atypical PAs make up 12.7% of all
      surgically treated PA cases, and they tend to be invasive and recurrent
      macroadenomas. We found no differences in metastatic potential between typical
      and atypical PA.

PMID- 26300500
TI  - Anticonvulsant activity of methanolic extract from Kalanchoe pinnata Lam. stems
      and roots in mice: A comparison to diazepam.
AB  - INTRODUCTION: In ancient and current traditional medicine in Mexico, extracts
      from the leaves or whole plant of 'life leaf' (Kalanchoe pinnata [K. pinnata]Lam)
      have been used to treat an entity known locally as 'yellow epilepsy' (alferecia
      amarilla) when it is accompanied by seizures. However, the anticonvulsive
      activity of its stems and roots remains unexplored METHODS: The anticonvulsant
      activity of the methanolic root extract (MER) or stem (MES) of K. pinnata Lam.
      was evaluated in a pentylenetetrazol-induced seizure model in Balb/C mice, and
      effects were compared to those of diazepam. The stem extract fractions that
      produced anticonvulsant activity were subsequently evaluated using the
      pentylenetetrazol -induced seizure model. RESULTS: We observed increased latency
      of tonic-clonic seizures that was inversely proportional to the dose of MRE, with
      a similar impact on the lethal effects of pentylenetetrazol. Different doses of
      the MSE showed a dose-dependent increase in latency to myoclonus, clonus, and
      tonic-clonic seizures, acting similarly to diazepam and offering 100% protection
      against the lethal effects of pentylenetetrazol. Fractioning MSE decreased its
      effectiveness, but when fractions were mixed with fractions of chloroform and
      ethyl acetate, anticonvulsive activity was restored. The preliminary
      phytochemical analysis identified alkaloids and sterols in MRE, and sterols and
      terpenes in MSE CONCLUSIONS: The anticonvulsant activity of K. pinnata Lam.
      decreases with increased doses of MRE, whereas the effect of MSE is dose
      dependent and preserved in the mixture chloroform and ethyl acetate. We suggest
      that the metabolites responsible for these effects are sterols in MRE, and
      sterols and terpenes in MSE.

PMID- 26300501
TI  - Physiological roles of relaxin in prefertilizing activities of spermatozoa.
AB  - Relaxin was first introduced in 1926 by Frederick Hisaw. Previously, it was
      considered only having a role in pregnancy of mammals due to its important roles
      in pregnancy and parturition. In the last decade, the physiological role of
      relaxin in male reproduction has received attention, and it has become clear that
      relaxin can no longer be considered strictly as only a hormone of female
      reproduction. The accessory glands (especially the prostate gland) of the male
      reproductive system are the source of seminal relaxin, which is secreted into the
      seminal plasma and saturates the spermatozoa at the time of ejaculation. Several
      studies have reported that relaxin has important roles in improving motility in
      human spermatozoa. Investigations into the role of relaxin in other physiological
      sperm phenomena such as capacitation, acrosome reaction, and their mediating
      factors associated with successful fertilization have intensified. This review
      aims to provide up-to-date information about the physiological roles of relaxin
      in sperm motility, capacitation, acrosome reaction, and their mediating factors.
      Some studies demonstrated that relaxin increased the total motility and
      progressive motility. Several studies showed that relaxin not only increased
      sperm motility but also increased the rate of sperm capacitation and acrosome
      reaction. Though few studies revealed that relaxin improved the sperm
      prefertilizing activities through increasing the utilization of glucose and
      mediating the cholesterol efflux, Ca(2+)-influx, intracellular cAMP and protein
      tyrosine phosphorylation. Thus, the review concludes that the supplementation of
      relaxin into capacitating medium may have a beneficial role in prefertilizing
      activities of fresh and cryopreserved spermatozoa. 

PMID- 26300502
TI  - [Report of the ordinary general assembly of the Morphologists' Association - 30th
      January 2015].

PMID- 26300503
TI  - Nefrologia: International Journal.

PMID- 26300504
TI  - Reflections on two consensus documents about chronic kidney disease.

PMID- 26300505
TI  - Cellular and molecular aspects of diabetic nephropathy; the role of VEGF-A.
AB  - The prevalence of diabetes mellitus increased during the last century and it is
      estimated that 45% of the patients are not diagnosed. In South America the
      prevalence of diabetes and chronic kidney disease (CKD) increased, with a great
      disparity among the countries with respect to access to dialysis. In Ecuador it
      is one of the main causes of mortality, principally in the provinces located on
      the coast of the Pacific Ocean. The greatest single cause of beginning dialysis
      is diabetic nephropathy (DN). Even using the best therapeutic options for DN, the
      residual risk of proteinuria and of terminal CKD remains high. In this review we
      indicate the importance of the problem globally and in our region. We analyse
      relevant cellular and molecular studies that illustrate the crucial significance
      of glomerular events in DN development and evolution and in insulin resistance.
      We include basic anatomical, pathophysiological and clinical concepts, with
      special attention to the role of angiogenic factors such as the vascular
      endothelial growth factor (VEGF-A) and their relationship to the insulin
      receptor, endothelial isoform of nitric oxide synthase (eNOS) and angiopoietins.
      We also propose various pathways that have therapeutic potential in our opinion.
      Greater in-depth study of VEGF-A and angiopoietins, the state of glomerular VEGF
      resistance, the relationship of VEGF receptor 2/nephrin, VEGF/insulin
      receptors/nephrin and the relationship of VEGF/eNOS-NO at glomerular level could
      provide solutions to the pressing world problem of DN and generate new treatment
      alternatives. 

PMID- 26300506
TI  - Hypertension in the African American population: A succinct look at its
      epidemiology, pathogenesis, and therapy.
AB  - Arterial hypertension is prevalent in the black population in the United States.
      It is directly related to cardiovascular and kidney damage. Its pathogenesis is
      complex and includes the high incidence of obesity, salt sensitivity and the
      activation of the renin-angiotensin-aldosterone system. This complexity requires
      a therapeutic combination that includes changes in dietary habits and appropriate
      antihypertensive regimes. The International Society of Hypertension in Blacks
      recommends initiating dietary intervention for values of systolic/diastolic
      arterial blood pressure above 115/75 mmHg and maintaining arterial blood pressure
      below 135/85 mmHg using appropiate antihypertensive medication. The most adequate
      antihypertensive drug for this population has yet to be determined.

PMID- 26300507
TI  - Palliative peritoneal dialysis: Implementation of a home care programme for
      terminal patients treated with peritoneal dialysis (PD).
AB  - Terminal-stage patients on peritoneal dialysis (PD) are often transferred to
      haemodialysis as they are unable to perform the dialysis technique themselves
      since their functional capacities are reduced. We present our experience with
      five patients on PD with a shortterm life-threatening condition, whose treatment
      was shared by primary care units and who were treated with a PD modality adapted
      to their circumstances, which we call Palliative Peritoneal Dialysis.

PMID- 26300508
TI  - The effect of some medications given to CKD patients on vitamin D levels.
AB  - BACKGROUND: Vitamin D deficiency and polypharmacy is a common problem over
      chronic kidney disease (CKD) population. OBJECTIVES: To assess the clinical and
      analytical characteristics of CKD patients with 25-OH-D3 deficiency (<15 ng/mL),
      including the possible role of associated drugs. METHODS: A single center
      observational review of 137 incident patients referred to our outpatient clinic
      with different stages of CKD and 25-OH-D3<15ng/mL (male gender 53.3%, mean age
      70.8 [+/-16.1] years, mean GFR (MDRD-4) 43.6 [+/-25.5] ml/min/1.73 m2). 25-OH-D3
      levels were collected in spring. Clinical and biochemical data and associated
      medications were recorded. RESULTS: Mean 25-OH-D3 levels were 8.23 [+/-4.03]
      ng/ml. Eighty-eight patients (64.7%) had 3 or more concomitant drugs. Only 7
      patients (5.1%) were not receiving any medication. Patients were divided in three
      groups according the therapies into none (n=26), RAS inhibitors or allopurinol
      (n=81), and RAS inhibitors plus allopurinol (n=30); with the aim to study the
      influence of statin therapy. Patients under renin angiotensin (RAS) inhibitors or
      Allopurinol treatment presented significantly higher 25-OH-D3 levels (p=0.001 and
      p=0.01 respectively), however patients with Statins treatment had lower 25-OH-D3
      level (p=0.039). Personal history of diabetes, cardiovascular events or other
      therapies did not modify 25-OH-D3 levels, adjusted by age and eGFR. CONCLUSIONS:
      CKD patients with vitamin D deficiency who received RAS inhibitors or Allopurinol
      treatment had higher 25-OH-D3 levels, however those with statins treatment had
      lower vitamin D levels. Randomized controlled trials are required to confirm
      these findings.

PMID- 26300509
TI  - Valvular calcifications at the start of dialysis predict the onset of
      cardiovascular events in the course of follow-up.
AB  - OBJECTIVE: To analyse the presence of VC at the start of dialysis and its
      relationship with events and/or death from cardiovascular causes in the course of
      follow-up. METHODS: In the study, we included patients who started dialysis
      between November 2003 and September 2007. In the first month of treatment, we
      assessed the presence of VC by Doppler echocardiography, along with demographic
      factors and risk factors for cardiovascular disease, coronary artery disease,
      stroke, atrial fibrillation (AF), and cardiac dimensional and functional
      electrocardiographic and echocardiographic parameters. The biochemistry values
      assessed were: haemoglobin, calcium/phosphorous/iPTH metabolism, cholesterol and
      fractions, triglycerides, troponin I, albumin, CRP and glycosylated haemoglobin.
      We analysed the association between VC and the presence of myocardial infarction
      (MI), stroke and/or death from cardiovascular causes up to transplantation, death
      or the end of the study (December 2012). RESULTS: Of 256 enrolled patients (83%
      haemodialysis, 17% peritoneal dialysis), 128 (50%) had VC (mitral: 39, aortic:
      20, both: 69). In the multivariate analysis, VC was associated with older age
      (OR: 1.110; 95% CI: 1.073-1.148; p = 0.000) and lower albumin levels (OR: 0.29;
      95% CI: 0.14-0.61; p = 0.001). In a follow-up lasting 42.1 +/- 30.2 months (898.1
      patient-years), 68 patients suffered MI, stroke and/or died from cardiovascular
      causes. In the Cox regression analysis, older age (HR: 1.028; 95% CI: 1.002
      1.055; p = 0.037), coronary artery disease and/or stroke (HR: 1.979; 95% CI:
      1.111-3.527; p = 0.021), AF (HR: 2.474; 95% CI: 1.331-4.602; p = 0.004), and the
      presence of VC at the start of dialysis (HR: 1.996; 95% CI: 1.077-3.700; p =
      0.028) were the predictor variables for the occurrence of the analysed events.
      CONCLUSIONS: The prevalence of VC at the start of dialysis is high and its
      presence predicts the occurrence of events and/or cardiovascular death in the
      course of follow-up.

PMID- 26300510
TI  - Acute effect of citrate bath on postdialysis alkalaemia.
AB  - INTRODUCTION: The correction of metabolic acidosis caused by renal failure is
      achieved by adding bicarbonate during dialysis. In order to avoid the
      precipitation of calcium carbonate and magnesium carbonate that takes place in
      the dialysis fluid (DF) when adding bicarbonate, it is necessary to add an acid,
      usually acetate, which is not free of side effects. Thus, citrate appears as an
      advantageous alternative to acetate, despite the fact that its acute effects are
      not accurately known. OBJECTIVE: To assess the acute effect of a dialysis fluid
      containing citrate instead of acetate on acid-base balance and calcium-phosphorus
      metabolism parameters. MATERIAL AND METHODS: A prospective crossover study was
      conducted with twenty-four patients (15 male subjects and 9 female subjects). All
      patients underwent dialysis with AK-200-Ultra-S monitor with SoftPac(r) dialysis
      fluid, made with 3 mmol/L of acetate and SelectBag Citrate(r), with 1 mmol/L of
      citrate and free of acetate. The following were measured before and after
      dialysis: venous blood gas monitoring, calcium (Ca), ionic calcium (Cai),
      phosphorus (P) and parathyroid hormone (PTH). RESULTS: Differences (p<0.05) were
      found when using the citrate bath (C) compared to acetate (A) in the postdialysis
      values of: pH, C: 7.43 (0.04) vs. A: 7.47 (0.05); bicarbonate, C: 24.7 (2.7) vs.
      A: 27.3 (2.1) mmol/L; base excess (BEecf), C: 0.4 (3.1) vs. A: 3.7 (2.4) mmol/L;
      corrected calcium (Cac), C: 9.8 (0.8) vs. A: 10.1 (0.7) mg/dL; and Cai, C: 1.16
      (0.05) vs. A: 1.27 (0.06) mmol/L. No differences were found in either of the
      parameters measured before dialysis. CONCLUSION: Dialysis with citrate provides
      better control of postdialysis acid-base balance, decreases/avoids postdialysis
      alkalaemia, and lowers the increase in Cac and Cai. This finding is of special
      interest in patients with predisposing factors for arrhythmia and patients with
      respiratory failure, carbon dioxide retention, calcifications and advanced liver
      disease.

PMID- 26300511
TI  - Urinary Klotho measured by ELISA as an early biomarker of acute kidney injury in
      patients after cardiac surgery or coronary angiography.
AB  - BACKGROUND: Acute kidney injury (AKI) is a common complication after cardiac
      surgery and percutaneous coronary interventions which markedly worsens prognosis.
      In recent years, new early biomarkers of AKI have been identified, but many
      important aspects still remain to be solved. Klotho is a pleiotropic protein that
      acts as a paracrine and endocrine factor in multiple organs. Reduced renal Klotho
      levels have been show in several animal models of AKI. No study has been
      published in which Klotho was tested in humans as an early marker of AKI. The aim
      of this work is to assess the usefulness of measuring urinary Klotho for the
      early diagnosis of AKI in patients with acute coronary syndrome or heart failure
      undergoing cardiac surgery or coronary angiography. METHODS: Urinary Klotho was
      measured 12 hours after intervention in 60 patients admitted to the Intensive
      Care Unit with acute coronary syndrome or heart failure secondary to coronary or
      valvular conditions, who underwent coronary angiography (30 patients) or cardiac
      bypass surgery or heart valve replacement (30 patients). The primary endpoint
      used was the onset of AKI according to the RIFLE classification system. Human
      Klotho levels were measured using an ELISA assay. RESULTS: We found no
      differences in urinary Klotho levels between AKI patients and those who did not
      develop AKI. Moreover, there was not significant correlation between urinary
      Klotho levels and the presence of AKI. CONCLUSION: Urinary Klotho measured by
      ELISA does not seem to be a good candidate to be used as an early biomarker of
      AKI.

PMID- 26300512
TI  - Clinical impact of the ERBP Working Group 2010 Recommendations for the anemia
      management in chronic kidney disease not on dialysis: ACERCA study.
AB  - BACKGROUND AND OBJECTIVE: The Anemia Working Group of ERBP in 2010 recommended a
      target hemoglobin (Hb) level in the range of 11-12 g/dL, without intentionally
      exceeding 13 g/dL during the treatment with erythropoiesis stimulating agents
      (ESAs). This study evaluated if there was a clinical impact of this statement in
      the anemia management of chronic kidney disease (CKD) patients treated with ESAs
      not on dialysis in routine clinical practice in Spain. METHODS: This was an
      observational and cross-sectional study carried out in CKD patients not on
      dialysis in Spain who initiated ESA treatment (naive), or were shifted from a
      previous ESA to another ESAs (converted) since January 2011. RESULTS: Of 441
      patients evaluated, 67.6% were naive and 32.4% were converted. At the study
      visit, 42.5% of naive patients achieved the Hb target of 11-12 g/dL, with a mean
      Hb of 11.3+/-1.3 g/dL (vs 10.1+/-0.9 g/dL at the start of ESA therapy). Only
      35.3% of converted patients maintained Hb levels within the recommended target at
      the study visit. Yet, 8.2% of naive patients and 7.9% of those converted had Hb
      levels >13 g/dL. Hb levels were similar across subgroups of patients, regardless
      of the presence of significant comorbidities. CONCLUSIONS: Anemia management in
      CKD patients treated with ESAs by Spanish nephrologists seems to be aimed at
      preventing Hb levels <11 g/dL, while <50% of patients were within the narrow
      recommended Hb target range. This, together with the lack of individualization in
      Hb targets according to patients' comorbidities show that there is still room for
      improvement in renal anemia management in the clinical setting.

PMID- 26300513
TI  - Overhydration prevalence in peritoneal dialysis - A 2 year longitudinal analysis.
AB  - BACKGROUND AND OBJECTIVES: Hypervolemia is a major concern in dialysis patients,
      and is associated with increased cardiovascular risk and death. Cross sectional
      analysis have previously demonstrated that peritoneal dialysis (PD) patients are
      not more overhydrated when compared to haemodialysis ones. This study was
      designed to evaluate longitudinal trends in hydration status and corporal
      composition in a PD population. METHODS: We conducted a 2 year prospective
      observational study of 58 PD patients from a single centre. Incident and
      prevalent patients were included. Yearly measurements were performed using
      multifrequency electric bioimpedance. Overhydration (OH) was defined as an extra
      cellular water (ECW)/total body water (TBW) over 15%. Clinical and biochemical
      variables were also explored. RESULTS: A total of 30 patients completed
      evaluation (female 63.3%, mean age 56.9 years, BMI 25.0 kg/m2, diabetes 10.0%,
      APD-50.0%). Median PD vintage was 21.9 months, and 36.7% were anuric. At baseline
      6.7% were overhydrated. On longitudinal analysis no significant changes were
      found in hydration status, systolic blood pressure, pro-BNP, nor albumin levels.
      Similar results were found among incident (n=11; APD- 45.5%; anuric- 9.1%) and
      prevalent (n=19; APD- 52.6%; anuric- 52.6%) patients (p>.05). However, at the
      second year, prevalent patients were moderately overhydrated compared to incident
      ones (median 10.2% vs 3.5%; p=.009). Nonetheless, no statistical difference was
      observed considering adequacy, TBW, or ECW. Moreover, nutritional parameters
      remained stable. CONCLUSIONS: Peritoneal dialysis maintenance without increasing
      volume status, nor major deleterious corporal composition trends, is feasible
      under careful therapy strategies. Longitudinal application of BIA may be a useful
      clinical tool to evaluate adequacy beyond Kt/V.

PMID- 26300514
TI  - Acute kidney injury secondary to a combination of renin-angiotensin system
      inhibitors, diuretics and NSAIDS: "The Triple Whammy".
AB  - BACKGROUND: Renin-angiotensin system inhibitors (ACEI/ARB-II), diuretics and
      NSAIDs, a combination known as "Triple Whammy", can result in decreased
      glomerular filtration rate (GFR) and acute kidney injury (AKI). Objectives: To
      describe the incidence of AKI for each drug type and their combinations. To
      define the profile of patients admitted for drug-related AKI secondary to Triple
      Whammy drugs (AKITW), with an assessment of costs and mortality. METHODS: A
      retrospective observational 15-month study developed in three stages: - First: a
      cross-sectional stage to identify and describe hospitalizations due to AKITW. -
      Second: a follow-up stage of an outpatient cohort consuming these drugs (15,307
      subjects). - Third: a cohort stage to assess costs and mortality, which compared
      62 hospitalized patients with AKITW and 62 without AKI, paired by medical
      specialty, sex, age and comorbidity according to their Clinical Risk Groups.
      RESULTS: There were 85 hospitalization episodes due to AKITW, and 78% of patients
      were over the age of 70. The incidence of AKITW in the population was 3.40
      cases/1000 users/year (95% CI: 2.59-4.45). By categories, these were: NSAIDs +
      diuretics 8.99 (95% CI: 3.16-25.3); Triple Whammy 8.82 (95% CI: 4.4-17.3);
      ACEI/ARB-II + diuretics 6.87 (95% CI: 4.81-9.82); and monotherapy with diuretics
      3.31 (95% CI: 1.39-7.85). Mean hospital stay was 7.6 days (SD 6.4), and mean
      avoidable costs were estimated at ?214,604/100,000 inhabitants/year. Mortality
      during hospitalization and at 12 months was 11.3% and 38.7% respectively, and
      there were no significant differences when compared with the control group.
      CONCLUSIONS: Treatment with ACEI, ARB-II, diuretics and/or NSAIDs shows a high
      incidence of hospitalization episodes due to AKI; diuretics as monotherapy or
      dual and triple combination therapy cause the highest incidence. AKITW involves
      high health care costs and avoidable mortality.

PMID- 26300515
TI  - Use of sevelamer in chronic kidney disease: beyond phosphorus control.
AB  - Sevelamer is a non-calcium phosphate binder used in advanced chronic kidney
      disease (CKD) and in dialysis for hyperphosphataemia control. Several
      experimental, observational studies and clinical trials have shown that sevelamer
      has pleiotropic effects, beyond hyperphosphataemia control, including actions on
      inflammation, oxidative stress, lipid profile and atherogenesis, vascular
      calcification, endothelial dysfunction and the reduction of several uremic
      toxins. This is the biological basis for its global effect on cardiovascular
      morbidity and mortality in patients with chronic kidney disease. This review
      focuses on these pleiotropic actions of sevelamer and their impact on
      cardiovascular health, with the experience published after more than ten years of
      clinical expertise.

PMID- 26300516
TI  - IgG4-related disease: description of a case with pulmonary lesions, mediastinal
      lymphadenopathies and rapidly progressive renal failure.
AB  - This is a case report of a 73-year-old man with new-onset acute renal failure
      while being investigated for pulmonary infiltrates and mediastinal
      lymphadenopathies. Urine tests showed tubular range proteinuria with no
      microhaematuria. Immunology tests showed elevated serum IgG and
      hypocomplementaemia (classical pathway activation). Renal biopsy and clinical
      pathological correlation were crucial in this case, reinforcing their important
      role in the final diagnosis of acute kidney injury.

PMID- 26300517
TI  - Acute kidney injury secondary to very severe hypercalcaemic crisis caused by
      primary hyperparathyroidism.

PMID- 26300518
TI  - Nursing interventions for substance use during psychiatric hospital admissions:
      Clinical context and predictors.
AB  - Empirical information about how nurses manage substance use on psychiatric wards
      is lacking. The aims of the study were to identify the frequency and clinical
      features of incidents among a sample of inpatients over a 12-month period and how
      nursing staff intervened. Electronic, anonymized inpatient records were searched
      for incidents of substance use on 17 acute psychiatric wards in four hospitals in
      London. Searches were conducted for all patients admitted during 2012 and details
      of incidents and patient characteristics were extracted for analysis. Substance
      use was reported for 291 patients, with 25 incidents per 100 patients admitted to
      hospital. Only half of the incidents were followed by a response that
      specifically addressed the patients' substance use behaviour. These interactions
      usually concerned the circumstances and reasons for use, but rarely involved
      specific support for patients' substance use problems. The likelihood of staff
      taking any form of action was increased if the patient had been formally
      admitted, and was reduced if the patient was subject to containment during the
      shift or had a history of self-harm. The results demonstrate that nurses require
      specific training and guidance on supporting substance using patients. 

PMID- 26300519
TI  - A systematic review and meta-regression analysis of prophylactic gabapentin for
      postoperative pain.
AB  - We searched MEDLINE, Embase, CINAHL, AMED and CENTRAL databases until December
      2014 and included 133 randomised controlled trials of peri-operative gabapentin
      vs placebo. Gabapentin reduced mean (95% CI) 24-h morphine-equivalent consumption
      by 8.44 (7.26-9.62) mg, p < 0.001, whereas more specific reductions in morphine
      equivalents were predicted (R(2)  = 90%, p < 0.001) by the meta-regression
      equation: 3.73 + (-0.378 * control morphine consumption (mg)) + (-0.0023 *
      gabapentin dose (mg)) + (-1.917 * anaesthetic type), where 'anaesthetic type' is
      '1' for general anaesthesia and '0' for spinal anaesthesia. The type of surgery
      was not independently associated with gabapentin effect. Gabapentin reduced
      postoperative pain scores on a 10-point scale at 1 h, 2 h, 6 h, 12 h and 24 h by
      a mean (95% CI) of: 1.68 (1.35-2.01); 1.21 (0.88-1.55); 1.28 (0.98-1.57); 1.12
      (0.91-1.33); and 0.71 (0.56-0.87), respectively, p < 0.001 for all. The risk
      ratios (95% CI) for postoperative nausea, vomiting, pruritus and sedation with
      gabapentin were: 0.78 (0.69-0.87), 0.67 (0.59-0.76), 0.64 (0.51-0.80) and 1.18
      (1.09-1.28), respectively, p < 0.001 for all. Gabapentin reduced pre-operative
      anxiety and increased patient satisfaction on a 10-point scale by a mean (95% CI)
      of 1.52 (0.78-2.26) points and 0.89 (0.22-1.57) points, p < 0.001 and p = 0.01,
      respectively. All the effects of gabapentin may have been overestimated by
      statistically significant small study effects. 

PMID- 26300520
TI  - Differentiation of ovarian development and the evolution of fecundity in rapidly
      diverging exotic beetle populations.
AB  - Fecundity is a fundamental determinant of fitness, yet the proximate
      developmental and physiological mechanisms that enable its often rapid evolution
      in natural populations are poorly understood. Here, we investigated two
      populations of the dung beetle Onthophagus taurus that were established in exotic
      ranges in the early 1970s. These populations are subject to drastically different
      levels of resource competition in the field, and have diverged dramatically in
      female fecundity. Specifically, Western Australian O. taurus experience high
      levels of resource competition, and exhibit greatly elevated reproductive output
      compared to beetles from the Eastern US, where resource competition is minimal
      and female fecundity is low. We compared patterns of ovarian maturation, relative
      investment into and timing of egg production, and potential trade-offs between
      ovarian investment and the duration of larval development and adult body size
      between populations representative of both exotic ranges. We found that the rapid
      divergence in fecundity between exotic populations is associated with striking
      differences in several aspects of ovarian development: (1) Western Australian
      females exhibit accelerated ovarian development, (2) produce more eggs, (3)
      bigger eggs, and (4) start laying eggs earlier compared to their Eastern US
      counterparts. At the same time, divergence in ovarian maturation patterns
      occurred alongside changes in (5) larval developmental time, and (6) adult body
      size, and (7) mass. Western Australian females take longer to complete larval
      development and, surprisingly, emerge into smaller yet heavier adults than size
      matched Eastern US females. We discuss our results in the context of the
      evolutionary developmental biology of fecundity in exotic populations.

PMID- 26300521
TI  - Combined spectroscopies and molecular docking approach to characterizing the
      binding interaction between lisinopril and bovine serum albumin.
AB  - To further understand the mode of action and pharmacokinetics of lisinopril, the
      binding interaction of lisinopril with bovine serum albumin (BSA) under imitated
      physiological conditions (pH 7.4) was investigated using fluorescence emission
      spectroscopy, synchronous fluorescence spectroscopy, Fourier transform infrared
      spectroscopy (FTIR), circular dichroism (CD) and molecular docking methods. The
      results showed that the fluorescence quenching of BSA near 338 nm resulted from
      the formation of a lisinopril-BSA complex. The number of binding sites (n) for
      lisinopril binding on subdomain IIIA (site II) of BSA and the binding constant
      were ~ 1 and 2.04 * 10(4) M(-1), respectively, at 310 K. The binding of
      lisinopril to BSA induced a slight change in the conformation of BSA, which
      retained its alpha-helical structure. However, the binding of lisinopril with BSA
      was spontaneous and the main interaction forces involved were van der Waal's
      force and hydrogen bonding interaction as shown by the negative values of
      DeltaG(0), DeltaH(0) and DeltaS(0) for the binding of lisinopril with BSA. It was
      concluded from the molecular docking results that the flexibility of lisinopril
      also played an important role in increasing the stability of the lisinopril-BSA
      complex.

PMID- 26300522
TI  - Healthcare transition challenges faced by young adults with autism spectrum
      disorder.
AB  - Autism spectrum disorder (ASD) is a neurodevelopmental disorder that impacts
      communicative interactions, with patterns of repetitive and restricted behaviors,
      interests, and cognitive rigidity. Recent incidence rate estimates for ASD are 1
      in 68, and primarily male (4:1). A major epidemiological issue in ASD is
      transitioning to independence in adulthood, particularly navigating the
      healthcare system. This commentary will focus on approaches healthcare providers
      can use to not overlook and support individuals with ASD. 

PMID- 26300523
TI  - [The role of uric acid in the insulin resistance in children and adolescents with
      obesity].
AB  - OBJECTIVE: To investigate the association between serum uric acid levels and
      insulin resistance in children and adolescents with obesity. METHODS: Cross
      sectional study with 245 children and adolescents (134 obese and 111 controls),
      aged 8 to 18 years. The anthropometric variables (weight, height and waist
      circumference), blood pressure and biochemical parameters were collected. The
      clinical characteristics of the groups were analyzed by t-test or chi-square
      test. To evaluate the association between uric acid levels and insulin resistance
      the Pearson's test and logistic regression were applied. RESULTS: The prevalence
      of insulin resistance was 26.9%. The anthropometric variables, systolic and
      diastolic blood pressure and biochemical variables were significantly higher in
      the obese group (p<0.001), except for the high-density-lipoprotein cholesterol.
      There was a positive and significant correlation between anthropometric variables
      and uric acid with HOMA-IR in the obese and in the control groups, which was
      higher in the obese group and in the total sample. The logistic regression model
      that included age, gender and obesity, showed an odds ratio of uric acid as a
      variable associated with insulin resistance of 1.91 (95%CI 1.40 to 2.62; p<
      0.001). CONCLUSIONS: The increase in serum uric acid showed a positive
      statistical correlation with insulin resistance and it is associated with and
      increased risk of insulin resistance in obese children and adolescents.

PMID- 26300524
TI  - [Speech and language disorders in children from public schools in Belo
      Horizonte].
AB  - OBJECTIVE: To investigate the prevalence of oral language, orofacial motor skill
      and auditory processing disorders in children aged 4-10 years old and verify
      their association with age and gender. METHODS: Cross-sectional study with
      stratified, random sample consisting of 539 students. The evaluation consisted of
      three protocols: orofacial motor skill protocol, adapted from the Myofunctional
      Evaluation Guidelines; the Child Language Test ABFW--Phonology, and a simplified
      auditory processing evaluation. Descriptive and associative statistical analyses
      were performed using Epi Info software, release 6.04. Chi-square test was applied
      to compare proportion of events and analysis of variance was used to compare mean
      values. Significance was set at p<=0.05. RESULTS: Of the studied subjects, 50.1%
      had at least one of the assessed disorders; of those, 33.6% had oral language
      disorder, 17.1%, had orofacial motor skill impairment, and 27.3% had auditory
      processing disorder. There were significant associations between auditory
      processing skills' impairment, oral language impairment and age, suggesting a
      decrease in the number of disorders with increasing age. Similarly, the variable
      "one or more speech, language and hearing disorders" was also associated with
      age. CONCLUSIONS: The prevalence of speech, language and hearing disorders in
      children was high, indicating the need for research and public health efforts to
      cope with this problem.

PMID- 26300525
TI  - Syndecan-1 identifies and controls the frequency of IL-17-producing naive natural
      killer T (NKT17) cells in mice.
AB  - Invariant natural killer T (iNKT) cells recognize glycolipids as antigens and
      diversify into NKT1 (IFN-gamma), NKT2 (IL-4), and NKT17 (IL-17) functional
      subsets while developing in the thymus. Mechanisms that govern the balance
      between these functional subsets are poorly understood due, partly, to the lack
      of distinguishing surface markers. Here we identify the heparan sulfate
      proteoglycan syndecan-1 (sdc1) as a specific marker of naive thymic NKT17 cells
      in mice and show that sdc1 deficiency significantly increases thymic NKT17 cells
      at the expense of NKT1 cells, leading to impaired iNKT cell-derived IFN-gamma,
      both in vitro and in vivo. Using surface expression of sdc1 to identify NKT17
      cells, we confirm differential tissue localization and interstrain variability of
      NKT17 cells, and reveal that NKT17 cells express high levels of TCR-beta,
      preferentially use Vbeta8, and are more highly sensitive to alpha-GalCer than to
      CD3/CD28 stimulation. These findings provide a novel, noninvasive, simple method
      for identification, and viable sorting of naive NKT17 cells from unmanipulated
      mice, and suggest that sdc1 expression negatively regulates homeostasis in iNKT
      cells. In addition, these findings lay the groundwork for investigating the
      mechanisms by which sdc1 regulates NKT17 cells. 

PMID- 26300526
TI  - Free energy landscape of a minimalist salt bridge model.
AB  - Salt bridges are essential to protein stability and dynamics. Despite the
      importance, there has been scarce of detailed discussion on how salt bridge
      partners interact with each other in distinct solvent exposed environments. In
      this study, employing a recent generalized orthogonal space tempering (gOST)
      method, we enabled efficient molecular dynamics simulation of repetitive breaking
      and reforming of salt bridge structures within a minimalist salt-bridge model,
      the Asp-Arg dipeptide and thereby were able to map its detailed free energy
      landscape in aqueous solution. Free energy surface analysis shows that although
      individually-solvated states are more favorable, salt-bridge states still occupy
      a noticeable portion of the overall population. Notably, the competing forces,
      e.g. intercharge attractions that drive the formation of salt bridges and
      solvation forces that pull the charged groups away from each other, are
      energetically comparable. As the result, the salt bridge stability is highly
      tunable by local environments; for instance when local water molecules are
      perturbed to interact more strongly with each other, the population of the salt
      bridge states is likely to increase. Our results reveal the critical role of
      local solvent structures in modulating salt-bridge partner interactions and imply
      the importance of water fluctuations on conformational dynamics that involves
      solvent accessible salt bridge formations.

PMID- 26300527
TI  - Pancreatic Tissue Transplanted in TheraCyte Encapsulation Devices Is Protected
      and Prevents Hyperglycemia in a Mouse Model of Immune-Mediated Diabetes.
AB  - Type 1 diabetes (T1D) is characterized by destruction of glucose-responsive
      insulin-producing pancreatic beta-cells and exhibits immune infiltration of
      pancreatic islets, where CD8 lymphocytes are most prominent. Curative
      transplantation of pancreatic islets is seriously hampered by the persistence of
      autoreactive immune cells that require high doses of immunosuppressive drugs. An
      elegant approach to confer graft protection while obviating the need for
      immunosuppression is the use of encapsulation devices that allow for the transfer
      of oxygen and nutrients, yet prevent immune cells from making direct contact with
      the islet grafts. Here we demonstrate that macroencapsulation devices (TheraCyte)
      loaded with neonatal pancreatic tissue and transplanted into RIP-LCMV.GP mice
      prevented disease onset in a model of virus-induced diabetes mellitus.
      Histological analyses revealed that insulin-producing cells survived within the
      device in animal models of diabetes. Our results demonstrate that these
      encapsulation devices can protect from an immune-mediated attack and can contain
      a sufficient amount of insulin-producing cells to prevent overt hyperglycemia.

PMID- 26300529
TI  - Remembering your past: The effects of concussion on autobiographical memory
      recall.
AB  - To date, research focusing on long-term memory functioning post concussion is
      limited. The purpose of the current study was to investigate the effects of
      concussion on long-term episodic autobiographical memory, once acute
      postconcussive symptoms have abated. Individuals with and without a history of
      concussion were asked to recall autobiographical memories from different life
      periods. The details, self-reported vividness, ease of recall, and completeness
      of these memories were assessed. Results indicated that although both control and
      previously concussed participants were equally able to recall autobiographical
      memories from all life periods, the transcribed memories of previously concussed
      participants were less detailed, were less complex, and revealed less active
      involvement in recollection. Specifically, memories of control participants
      contained more words and a higher proportion of pronouns, personal pronouns,
      cognitive process words, perceptual process words, and past-tense words. Deficits
      were found regardless of the frequency or recency of concussion. Concussion
      information, limitations, and implications of the current findings are discussed.

PMID- 26300530
TI  - Microsatellite evidence for obligate autogamy, but abundant genetic variation in
      the herbaceous monocarp Lobelia inflata (Campanulaceae).
AB  - Although high levels of self-fertilization (>85%) are not uncommon in nature,
      organisms reproducing entirely through selfing are extremely rare. Predominant
      selfers are expected to have low genetic diversity because genetic variation is
      distributed among rather than within lineages and is readily lost through genetic
      drift. We examined genetic diversity at 22 microsatellite loci in 105 individuals
      from a population of the semelparous herb Lobelia inflata L. and found (i) no
      evidence of heterozygosity through outcrossing, yet (ii) high rates of genetic
      polymorphism (2-4 alleles per locus). Furthermore, this genetic variation among
      lineages was associated with phenotypic traits (e.g. flower colour, size at first
      flower). Coupled with previous work characterizing the fitness consequences of
      reproductive timing, our results suggest that temporal genotype-by-environment
      interaction may maintain genetic variation and, because genetic variation occurs
      only among lineages, this simple system offers a unique opportunity for future
      tests of this mechanism.

PMID- 26300528
TI  - Food Avoidance Diets for Dermatitis.
AB  - Food allergy is relatively common in both children and adults, and its prevalence
      is increasing. Early exposure of food allergens onto skin with an impaired
      epidermal barrier predisposes to sensitization and prevents the development of
      oral tolerance. While immediate-type food allergies are well described, less is
      known about delayed-type food allergies manifesting as dermatitis. This is due,
      in part, to limitations with current diagnostic testing for delayed-type food
      allergy, including atopy patch testing. We conducted a systematic review of food
      avoidance diets in delayed-type food allergies manifesting as dermatitis. While
      beneficial in some clinical circumstances, avoidance diets should be used with
      caution in infants and children, as growth impairment and developmental delay may
      result. Ultimately, dermatitis is highly multifactorial and avoidance diets may
      not improve symptoms of delayed-type food allergy until combined with other
      targeted therapies, including restoring balance in the skin microbiome and re
      establishing proper skin barrier function. 

PMID- 26300531
TI  - Phylogenetic characterization and promoter expression analysis of a novel hybrid
      protein disulfide isomerase/cargo receptor subfamily unique to plants and
      chromalveolates.
AB  - Protein disulfide isomerases (PDIs) play critical roles in protein folding by
      catalyzing the formation and rearrangement of disulfide bonds in nascent
      secretory proteins. There are six distinct PDI subfamilies in terrestrial plants.
      A unique feature of PDI-C subfamily members is their homology to the yeast
      retrograde (Golgi-to-endoplasmic reticulum) cargo receptor proteins, Erv41p and
      Erv46p. Here, we demonstrate that plant Erv41p/Erv46p-like proteins are divided
      into three subfamilies: ERV-A, ERV-B and PDI-C, which all possess the N-proximal
      and C-proximal conserved domains of yeast Erv41p and Erv46p. However, in PDI-C
      isoforms, these domains are separated by a thioredoxin domain. The distribution
      of PDI-C isoforms among eukaryotes indicates that the PDI-C subfamily likely
      arose through an ancient exon-shuffling event that occurred before the divergence
      of plants from stramenopiles and rhizarians. Arabidopsis has three PDI-C genes:
      PDI7, PDI12, and PDI13. PDI12- and PDI13-promoter: beta-glucuronidase (GUS) gene
      fusions are co-expressed in pollen and stipules, while PDI7 is distinctly
      expressed in the style, hydathodes, and leaf vasculature. The PDI-C thioredoxin
      domain active site motif CxxS is evolutionarily conserved among land plants.
      Whereas PDI12 and PDI13 retain the CxxS motif, PDI7 has a CxxC motif similar to
      classical PDIs. We hypothesize that PDI12 and PDI13 maintain the ancestral roles
      of PDI-C in Arabidopsis, while PDI7 has undergone neofunctionalization. The
      unusual PDI/cargo receptor hybrid arrangement in PDI-C isoforms has no
      counterpart in animals or yeast, and predicts the need for pairing redox
      functions with cargo receptor processes during protein trafficking in plants and
      other PDI-C containing organisms. 

PMID- 26300532
TI  - Long-term mortality of hospitalized pneumonia in the EPIC-Norfolk cohort.
AB  - Little is known about cause-specific long-term mortality beyond 30 days in
      pneumonia. We aimed to compare the mortality of patients with hospitalized
      pneumonia compared to age- and sex-matched controls beyond 30 days. Participants
      were drawn from the European Prospective Investigation into Cancer (EPIC)-Norfolk
      prospective population study. Hospitalized pneumonia cases were identified from
      record linkage (ICD-10: J12-J18). For this study we excluded people with
      hospitalized pneumonia who died within 30 days. Each case identified was matched
      to four controls and followed up until the end June 2012 (total 15 074 person
      years, mean 6.1 years, range 0.08-15.2 years). Cox regression models were
      constructed to examine the all-cause, respiratory and cardiovascular mortality
      using date of pneumonia onset as baseline with binary pneumonia status as
      exposure. A total of 2465 men and women (503 cases, 1962 controls) [mean age
      (s.d.) 64.5 (8.3) years] were included in the study. Between a 30-day to 1-year
      period, hazard ratios (HRs) of all-cause and cardiovascular mortality were 7.3
      [95% confidence interval (CI) 5.4-9.9] and 5.9 (95% CI 3.5-9.7), respectively
      (with very few respiratory deaths within the same period) in cases compared to
      controls after adjusting for age, sex, asthma, smoking status, pack years,
      systolic and diastolic blood pressure, diabetes, physical activity, waist-to-hip
      ratio, prevalent cardiovascular and respiratory diseases. All outcomes assessed
      also showed increased risk of death in cases compared to controls after 1 year;
      respiratory cause of death being the most significant during that period (HR
      16.4, 95% CI 8.9-30.1). Hospitalized pneumonia was associated with increased all
      cause and specific-cause mortality beyond 30 days. 

PMID- 26300533
TI  - Risk factors for early disability pension in patients with epilepsy and
      vocational difficulties - Data from a specialized rehabilitation unit.
AB  - PURPOSE: The purpose of this study was to assess the risk factors for early
      disability pension (EDP) in adult patients with epilepsy in a specialized
      epilepsy rehabilitation setting. METHODS: In a retrospective study, 246 patients
      with epilepsy and employment difficulties leading to referral to an inpatient
      rehabilitation unit were evaluated with a questionnaire on admission and after a
      mean of 2.5years after discharge. Patients already receiving EDP at baseline were
      excluded. Epilepsy-related, demographic, and employment-related data as well as
      cognitive functioning and psychiatric comorbidity were assessed as risk factors
      for EDP at follow-up and analyzed using logistic regression models. RESULTS:
      Seventy-six percent of the patients had uncontrolled epilepsy, and 66.7% had
      psychiatric comorbidity. At follow-up, 33.7% received an EDP. According to
      multivariate logistic regression analysis, age>50years (odds ratio (OR) 5.44,
      compared to age<30years), application for an EDP prior to admission (OR 3.7),
      sickness absence>3months in the previous year (OR 3.30, compared to sickness
      absence<3months), and psychiatric comorbidity (OR 2.79) were significant risk
      factors for an EDP at follow-up, while epilepsy-related factors and cognitive
      impairment showed an effect only in the univariate analyses. CONCLUSIONS:
      Potential risk factors for EDP in patients with epilepsy were evaluated using
      multivariate analysis. Knowledge of such factors may help to develop appropriate
      criteria for rehabilitation candidacy and interventions to reduce the risk for
      EDP. This might lead to an amelioration of both psychosocial burden of patients
      and economic burden on society.

PMID- 26300534
TI  - Functional substrate for memory function differences between patients with left
      and right mesial temporal lobe epilepsy associated with hippocampal sclerosis.
AB  - OBJECTIVE: Little is known about the functional substrate for memory function
      differences in patients with left or right mesial temporal lobe epilepsy (mTLE)
      associated with hippocampal sclerosis (HS) from an electrophysiological
      perspective. To characterize these differences, we hypothesized that hippocampal
      theta connectivity in the resting-state might be different between patients with
      left and right mTLE with HS and be correlated with memory performance. METHODS:
      Resting-state hippocampal theta connectivity, identified via whole-brain
      magnetoencephalography, was evaluated. Connectivity and memory function in 41
      patients with mTLE with HS (left mTLE=22; right mTLE=19) were compared with those
      in 46 age-matched healthy controls and 28 patients with focal cortical dysplasia
      (FCD) but without HS. RESULTS: Connectivity between the right hippocampus and the
      left middle frontal gyrus was significantly stronger in patients with right mTLE
      than in patients with left mTLE. Moreover, this connectivity was positively
      correlated with delayed verbal recall and recognition scores in patients with
      mTLE. Patients with left mTLE had greater delayed recall impairment than patients
      with right mTLE and FCD. Similarly, delayed recognition performance was worse in
      patients with left mTLE than in patients with right mTLE and FCD. No significant
      differences in memory function between patients with right mTLE and FCD were
      detected. Patients with right mTLE showed significantly stronger hippocampal
      theta connectivity between the right hippocampus and left middle frontal gyrus
      than patients with FCD and left mTLE. CONCLUSION: Our results suggest that right
      hippocampal-left middle frontal theta connectivity could be a functional
      substrate that can account for differences in memory function between patients
      with left and right mTLE. This functional substrate might be related to different
      compensatory mechanisms against the structural hippocampal lesions in left and
      right mTLE groups. Given the positive correlation between connectivity and
      delayed verbal memory function, hemispheric-specific hippocampal-frontal theta
      connectivity assessment could be useful as an electrophysiological indicator of
      delayed verbal memory function in patients with mTLE with HS.

PMID- 26300535
TI  - Sesamin prevents decline in exercise capacity and impairment of skeletal muscle
      mitochondrial function in mice with high-fat diet-induced diabetes.
AB  - NEW FINDINGS: What is the central question of this study? Our aim was to examine
      whether sesamin can prevent a decline in exercise capacity in high-fat diet
      induced diabetic mice. Our hypothesis was that maintenance of mitochondrial
      function and attenuation of oxidative stress in the skeletal muscle would
      contribute to this result. What is the main finding and its importance? The new
      findings are that sesamin prevents the diabetes-induced decrease in exercise
      capacity and impairment of mitochondrial function through the inhibition of
      NAD(P)H oxidase-dependent oxidative stress in the skeletal muscle. Sesamin may be
      useful as a novel agent for the treatment of diabetes mellitus. ABSTRACT: We
      previously reported that exercise capacity and skeletal muscle mitochondrial
      function in diabetic mice were impaired, in association with the activation of
      NAD(P)H oxidase. It has been reported that sesamin inhibits NAD(P)H oxidase
      induced superoxide production. Therefore, we examined whether the antioxidant
      sesamin could prevent a decline in exercise capacity in mice with high-fat diet
      (HFD)-induced diabetes. C57BL/6J mice were fed a normal diet (ND) or HFD, then
      treated or not with sesamin (0.2%) to yield the following four groups: ND,
      ND+Sesamin, HFD and HFD+Sesamin (n = 10 each). After 8 weeks, body weight, fat
      weight, blood glucose, insulin, triglyceride, total cholesterol and fatty acid
      were significantly increased in HFD compared with ND mice. Sesamin prevented the
      increases in blood insulin and lipid levels in HFD-fed mice, but did not affect
      the plasma glucose. Exercise capacity determined by treadmill tests was
      significantly reduced in HFD mice, but almost completely recovered in HFD+Sesamin
      mice. Citrate synthase activity was significantly decreased in the skeletal
      muscle of HFD mice, and these decreases were also inhibited by sesamin.
      Superoxide anion and NAD(P)H oxidase activity were significantly increased in HFD
      mice compared with the ND mice and were ameliorated by sesamin. Sesamin prevented
      the decline in exercise capacity in HFD-induced diabetic mice via maintenance of
      mitochondrial function, fat oxidation and attenuation of oxidative stress in the
      skeletal muscle. Our data suggest that sesamin may be useful as a novel agent for
      the treatment of diabetes mellitus.

PMID- 26300536
TI  - Dermoscopy of tumours arising in naevus sebaceous: a morphological study of 58
      cases.
AB  - BACKGROUND: Naevus sebaceous is a congenital hamartoma commonly associated with
      the development of secondary neoplasms. There are sparse data relating to the
      dermoscopy of tumours arising in naevus sebaceous. OBJECTIVES: To evaluate the
      dermoscopic features of a large series of neoplasms arising in naevus sebaceous.
      METHODS: Digital dermoscopic images of 58 histopathologically confirmed cases of
      secondary neoplasms arising in naevus sebaceous collected from 11 hospitals in
      Spain, France, Italy and Austria were evaluated for the presence of dermoscopic
      structures and patterns. RESULTS: The most frequent tumours collected were:
      trichoblastoma (39.6%), basal cell carcinoma (20.7%) and syringocystadenoma
      papilliferum (15.6%). The most remarkable findings were: (i) the pattern composed
      of asymmetrical large blue-grey ovoid nests was more common in basal cell
      carcinomas than in trichoblastoma (58.3% vs. 4.3%; P < 0.001) and the pattern
      composed of a symmetrical total large blue-grey ovoid nest (a blue-grey
      homogeneous area which occupies the whole lesion) was more common in
      trichoblastoma (82.6% vs. 16.6%; P < 0.001); (ii) the most frequent pattern
      associated with syringocystadenoma papilliferum was a symmetric, erythematous
      lesion with exophytic papillary structures, ulceration and vessels (55.5%); (iii)
      the most common pattern associated with apocrine hidrocystomas was a total
      symmetric homogeneous area and arborizing telangiectasias (60%). CONCLUSIONS:
      Benign adnexal tumours associated with naevus sebaceous are dermoscopic mimickers
      of basal cell carcinomas. A pigmented nodule arising in a naevus sebaceous with a
      total blue large ovoid nest on dermoscopy could be a trichoblastoma, basal cell
      carcinoma, hidrocystoma or hidradenoma. Dermoscopy can be a useful diagnostic
      tool which generates a more accurate preoperative diagnosis.

PMID- 26300537
TI  - Understanding physical activity in individuals with prediabetes: an application
      of social cognitive theory.
AB  - Despite well-documented evidence implicating physical activity (PA) in the
      prevention of type 2 diabetes, the overwhelming majority of individuals with
      prediabetes are not physically active enough. The purpose of this study was to
      investigate the applicability of the social cognitive theory (SCT) in
      understanding PA behaviour in individuals with prediabetes. Individuals with
      prediabetes (N = 232) completed a mailed questionnaire assessing demographics,
      self-reported PA (MET.min/wk) and SCT constructs for PA MET.min/wk. For PA
      MET.min/wk, scheduling and task efficacy both had significant effects on PA (beta
      = .30 and .22, respectively). Goal formation also had a direct effect on PA for
      scheduling, coping and task efficacy (beta = .20, .34 and .30, respectively).
      Task, coping and scheduling efficacy explained a significant portion of the
      variance in PA behaviour. Overall, SCT appears to have merit as a model for
      understanding PA in individuals with prediabetes. Further evaluative inquiry is
      needed to establish support for the use of the SCT as a framework for developing,
      implementing and evaluating PA behaviour change interventions in this population.

PMID- 26300539
TI  - Corrigendum: HPGCD Outperforms HPBCD as a Potential Treatment for Niemann-Pick
      Disease Type C During Disease Modeling with iPS Cells.

PMID- 26300538
TI  - Pre-clinical assessment of the effectiveness of modified polyvalent antivenom in
      the neutralization of Naja naja venom toxicity.
AB  - The potency of conventional antivenom (AV) conjugated to soy protein
      nanoparticles (NPs) (C-AV) was compared with the free AV in neutralizing the
      systemic toxicity of Naja naja venom. The effective dose (ED50 ) of AV and C-AV
      to neutralize the venom-induced toxicity in mice was found to be 19.89 and 9.50
      mg, respectively. The histopathological examination of heart, liver, and kidney
      indicated that the systemic toxicity induced by the venom was effectively
      neutralized by lower concentrations of C-AV than compared with AV. In addition, C
      AV was found to be more effective in neutralizing the edema forming activity of
      N. naja venom compared with the AV. Thus, the results of this study indicate that
      the potency of commercially available AV could be improved by conjugating it to
      soy protein NPs.

PMID- 26300540
TI  - Structural analysis of the mechanism of phosphorylation of a critical
      autoregulatory tyrosine residue in FGFR1 kinase domain.
AB  - Receptor and nonreceptor tyrosine kinases are enzymes that play important roles
      in regulating signal transduction pathways in a variety of normal cellular
      process and in many pathological conditions. Ordered phosphorylation is required
      for receptor tyrosine kinase (RTK) activation, a process mediated by transient
      dimer formation of the kinase domains. This process is triggered by the tyrosine
      phosphorylation in the activation loop. Here, we report structural and
      biochemical analyses of the tyrosine kinase domain interaction of fibroblast
      growth factor receptor 1 (FGFR1) required for the initial phosphorylation step.
      On the basis of nuclear magnetic resonance (NMR) analysis and covalent cross
      linking experiments, we propose a parallel symmetric dimer model where specific
      contacts are formed between the N-lobes and C-lobes, respectively, in the FGFR1
      kinase domains. Moreover, assignment of the contact sites between two FGFR1
      kinase domains are supported by a trans-phosphorylation assay and by mutational
      analyses. The present report shows the molecular mechanism underlying the control
      of trans-phosphorylation of a critical auto-regulatory site in FGF receptors'
      catalytic domain. 

PMID- 26300541
TI  - HINT1 is involved in the behavioral abnormalities induced by social isolation
      rearing.
AB  - Social isolation (SI) rearing has been demonstrated to induce behavioral
      abnormalities like anxiety, impulsivity, aggression, and learning and memory
      deficits which are relevant to core symptoms in patients with some certain
      neuropsychiatric disorders. But the underlying pathophysiological mechanisms
      remain unclear. Recent studies have revealed HINT1 has close relation with
      diverse neuropsychiatric diseases. In this present study, the SI rearing mice
      exhibited depression-like and aggressive behavior. Besides, HINT1 protein levels
      decreased in PFC but increased in HIP. Based on the data obtained, we concluded
      that HINT1 is involved in the behavioral abnormalities induced by social
      isolation and exerts distinct roles in different encephalic regions. 

PMID- 26300542
TI  - D620N mutation in the VPS35 gene and R1205H mutation in the EIF4G1 gene are
      uncommon in the Greek population.
AB  - Recently, vacuolar protein sorting 35 (VPS35) and eukaryotic translation
      initiation factor 4 gamma 1 (EIF4G1) have been identified as new causal
      Parkinson's disease (PD) genes, with the VPS35 D620N and EIF4G1 R1205H mutations
      being identified in both autosomal dominant late-onset familial and sporadic PD
      patients. However, the frequencies of these two mutations among different ethnic
      groups vary. We studied the VPS35 D620N and EIF4G1 R1205H mutations in a total of
      333 individuals, 202 Greek patients with sporadic PD and 131 control subjects,
      using a polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP) method. None of our studied individuals carried these two mutations. Our
      data support that the VPS35 D620N and EIF4G1 R1205H mutations are not a common
      cause of PD in the Greek population. 

PMID- 26300543
TI  - Salidroside attenuates lipopolysaccharide (LPS) induced serum cytokines and
      depressive-like behavior in mice.
AB  - The aim of the study was to investigate the effects and possible underlying
      mechanism of salidroside (Sal) on lipopolysaccharide (LPS)-induced depression
      like behavior in mice. Sal (12 mg/kg and 24 mg/kg) and fluoxetine (20 mg/kg) were
      administered intragastrically once daily for 5 days. At the 5th day, LPS (0.5
      mg/kg) was injected intraperitoneally 30 min after drug administration. Levels of
      interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha in serum were measured
      by ELISA. Levels of neurotransmitters like norepinephrine (NE) and 5
      hydroxytryptamine (5-HT) in the prefrontal cortex were detected by HPLC-MS.
      Further, brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B
      (TrkB) and Nuclear factor-kappaB (NF-kappaB) in hippocampal was determined by
      western blot analysis. Our data showed that pretreatment with Sal dramatically
      attenuated LPS-induced inflammatory response, decrease of NE and 5-HT levels in
      the prefrontal cortex. In addition, Sal increased expression levels of BNDF and
      TrkB. These results suggested that Sal may play a neuroprotective role through
      the BDNF/TrkB signaling pathway.

PMID- 26300544
TI  - OPRK1 promoter hypermethylation increases the risk of Alzheimer's disease.
AB  - As a member of the opioid family, kappa-opioid receptors play important role in
      cognitive and learning functions. The purpose of this study was to evaluate the
      association of OPRK1 promoter methylation with Alzheimer's disease (AD). OPRK1
      DNA methylation levels of 48 cases and 58 well matched controls were measured
      using the bisulphite pyrosequencing technology. Our results showed that there was
      a significant correlation between three CpG sites on the OPRK1 promoter region
      (r>=0.715, p<0.001). Thus, the mean methylation value of the three CpG sites was
      used for the case-control comparison. And our results showed there was a
      significantly higher OPRK1 promoter methylation in AD cases than in controls
      (p=0.006, adjusted p=0.012). Subsequent luciferase reporter assay showed the CpGs
      containing fragment of OPRK1 promoter significantly increased the expression of
      reporter gene (Fold=2.248, p=0.0235). In summary, our results suggested that
      OPRK1 promoter hypermethylation might increase the risk of AD through its
      regulation on the gene expression of OPRK1. 

PMID- 26300545
TI  - Evaluation of alginate-whey protein microcapsules for intestinal delivery of
      lipophilic compounds in pigs.
AB  - BACKGROUND: In animal care and management, there is an increasing demand for
      convenient methods of oral delivery of bioactive compounds to specific segments
      of an animal's gastrointestinal tract. The objective of this study was to test
      the suitability of microcapsules made with alginate and whey proteins of two
      different sizes (250 and 800 um; containing 72 and 76 g kg(-1) of carvacrol
      respectively) for intestinal delivery of carvacrol in pigs. RESULTS: Encapsulated
      carvacrol was completely released from the microcapsules after 5 h incubation in
      simulated intestinal fluids or 6 h in (ex vivo) ileal digesta, whereas release in
      simulated gastric fluid was minimal. Tests with growing pigs showed over 95% of
      unencapsulated carvacrol was absorbed or metabolized in the stomach and the
      duodenum. Encapsulation effectively minimized carvacrol absorption in the stomach
      (P < 0.05), and increased carvacrol recovery in the small intestine (P < 0.05).
      Encapsulated carvacrol was completely released from both small and large size
      capsules within the gastrointestinal tract of pigs. Larger size microcapsules
      showed a slower in vitro release and greater in vivo recovery of carvacrol in the
      small intestine (P < 0.05) than the smaller ones. CONCLUSION: This study
      indicates alginate-whey protein microencapsulation is a feasible approach for
      targeted oral delivery of hydrophobic compounds to pig intestines; increasing
      capsule size increased delivery of carvacrol to the end of the small intestine.
      (c) 2015 Her Majesty the Queen in Right of Canada Journal of the Science of Food
      and Agriculture (c) 2015 Society of Chemical Industry.

PMID- 26300546
TI  - Epirubicin inhibits growth and alters the malignant phenotype of the U-87 glioma
      cell line.
AB  - Epirubicin, an anthracycline derivative, is one of the main line treatments for
      brain tumors. The aim of the present study was to verify that epirubicin alters
      the growth and morphological characteristics of U-87 glioma cells. In the present
      study, the effects of epirubicin were tested using cellular and biochemical
      assays, which demonstrated its anti-proliferative and cytotoxic effects, with an
      IC50 of 6.3 uM for the U-87 cell line, while rat normal neuronal cells were
      resistant to epirubicin. Epirubicin also reduced the secretion of matrix
      metalloproteinase-9 by 48 and 56% at concentrations of 2.5 and 5 uM,
      respectively. Exposure to epirubicin also diminished levels of vascular
      endothelial growth factor in U-87 cells. Furthermore, a cell migration assay
      showed a significant decrease in cell migration from 28 to 59% following exposure
      to 1 uM epirubicin. The present study demonstrated the cytotoxic, anti
      proliferative and anti-migrative potential of epirubicin against glioma cells in
      vitro.

PMID- 26300547
TI  - MicroRNA regulation of the major drug-metabolizing enzymes and related
      transcription factors.
AB  - Identifying novel mechanisms contributing to patient variability of drug response
      is a major goal of personalized medicine. Epigenetic regulation of gene
      expression by microRNA (miRNA) impacts a broad range of cellular processes, but
      knowledge of its regulation of drug-metabolizing enzymes (DMEs) is more limited.
      This review provides an introduction to miRNA and their functionality and
      summarizes known miRNA regulation of DME families, including the cytochrome
      P450s, UDP-glucuronoslytransferases, glutathione-S-transferases,
      sulfotransferases and aldo-keto reductases, and the transcription factors known
      to be involved in DME regulation.

PMID- 26300549
TI  - Selective Formylation of Azacalixpyridine Macrocycles and Their Transformation to
      Molecular Semicages.
AB  - The aromatic electrophilic formylation reaction of azacalix[2]arene[2]pyridine
      and azacalix[4]pyridine were systematically studied. By simply controlling the
      ratio of reactants and the reaction temperature, the Vilsmeier-Haack reaction
      selectively afforded mono-, di-, and tetra-formylated
      azacalix[2]arene[2]pyridines and azacalix[4]pyridines. The preferential and
      selective functionalization reactions of macrocycles were discussed in terms of
      their conformational structure and conjugation effect between aromatic subunits
      and bridging nitrogen atoms. All resulting functionalized
      azacalix[2]arene[2]pyridines and azacalix[4]pyridines adopted a 1,3-alternate
      conformation both in the crystalline state and in solution. Taking advantage of
      the close proximity of aldehyde groups in 1,3-alternate di- and tetra-formylated
      azacalixpyridine macrocycles, the McMurry reductive coupling reaction of
      carbonyls was accomplished to yield unique semicage molecules. 

PMID- 26300550
TI  - Assessing the Risk of Secondary Transfer Via Fingerprint Brush Contamination
      Using Enhanced Sensitivity DNA Analysis Methods.
AB  - Experiments were performed to determine the extent of cross-contamination of DNA
      resulting from secondary transfer due to fingerprint brushes used on multiple
      items of evidence. Analysis of both standard and low copy number (LCN) STR was
      performed. Two different procedures were used to enhance sensitivity, post-PCR
      cleanup and increased cycle number. Under standard STR typing procedures, some
      additional alleles were produced that were not present in the controls or blanks;
      however, there was insufficient data to include the contaminant donor as a
      contributor. Inclusion of the contaminant donor did occur for one sample using
      post-PCR cleanup. Detection of the contaminant donor occurred for every replicate
      of the 31 cycle amplifications; however, using LCN interpretation recommendations
      for consensus profiles, only one sample would include the contaminant donor. Our
      results indicate that detection of secondary transfer of DNA can occur through
      fingerprint brush contamination and is enhanced using LCN-DNA methods. 

PMID- 26300548
TI  - The functional relevance of somatic synonymous mutations in melanoma and other
      cancers.
AB  - Recent technological advances in sequencing have flooded the field of cancer
      research with knowledge about somatic mutations for many different cancer types.
      Most cancer genomics studies focus on mutations that alter the amino acid
      sequence, ignoring the potential impact of synonymous mutations. However,
      accumulating experimental evidence has demonstrated clear consequences for gene
      function, leading to a widespread recognition of the functional role of
      synonymous mutations and their causal connection to various diseases. Here, we
      review the evidence supporting the direct impact of synonymous mutations on gene
      function via gene splicing; mRNA stability, folding, and translation; protein
      folding; and miRNA-based regulation of expression. These results highlight the
      functional contribution of synonymous mutations to oncogenesis and the need to
      further investigate their detection and prioritization for experimental
      assessment. 

PMID- 26300551
TI  - Raiders of the Lost Art: A review of published evaluations of inpatient mental
      health care experiences emanating from the United Kingdom, Portugal, Canada,
      Switzerland, Germany and Australia.
AB  - Forming interpersonal therapeutic relationships with mental health Service Users
      remains a key aspect of the practice of Psychiatric/Mental Health nurses. Given
      the omnipresence of the concept within the relevant literature the reader could
      be forgiven for asking: why would Psychiatric/Mental Health nurses opine about
      something so basic, so ubiquitous and so central to the theory and practice of
      our discipline? While the authors could locate no substantive argument that
      refutes the role or value of such relationships, a sizable, growing and
      reasonably consistent body of work has emerged, which appears to indicate that
      this centrality and value is not necessarily reflected in many clinical practice
      settings. Accordingly, we draw on the published evaluations of mental health care
      emanating from the United Kingdom, Portugal, Canada, Switzerland, Germany and
      Australia, compare these findings and highlight similarities or/and congruence
      and discuss a range of issues arising out of the findings. Alas, the findings
      seem to depict a mental health care inpatient experience that is often devoid of
      warm therapeutic relationships, respectful interactions, information or choice
      about treatment and any kind of formal/informal 'talk therapy'. Instead such care
      experiences are personified by: coercion, disinterest, inhumane practices,
      custodial and controlling practitioners and a gross over use of pharmacological
      'treatments'. 

PMID- 26300552
TI  - Mutations can cause light chains to be too stable or too unstable to form amyloid
      fibrils.
AB  - Light chain (AL) amyloidosis is an incurable human disease, where the amyloid
      precursor is a misfolding-prone immunoglobulin light-chain. Here, we identify the
      role of somatic mutations in the structure, stability and in vitro fibril
      formation for an amyloidogenic AL-12 protein by restoring four nonconservative
      mutations to their germline (wild-type) sequence. The single restorative
      mutations do not affect significantly the native structure, the unfolding
      pathway, and the reversibility of the protein. However, certain mutations either
      decrease (H32Y and H70D) or increase (R65S and Q96Y) the protein thermal
      stability. Interestingly, the most and the least stable mutants, Q96Y and H32Y,
      do not form amyloid fibrils under physiological conditions. Thus, Q96 and H32 are
      key residues for AL-12 stability and fibril formation and restoring them to the
      wild-type residues preclude amyloid formation. The mutants whose equilibrium is
      shifted to either the native or unfolded states barely sample transient partially
      folded states, and therefore do not form fibrils. These results agree with
      previous observations by our laboratory and others that amyloid formation occurs
      because of the sampling of partially folded states found within the unfolding
      transition (Blancas-Mejia and Ramirez-Alvarado, Ann Rev Biochem 2013;82:745-774).
      Here we provide a new insight on the AL amyloidosis mechanism by demonstrating
      that AL-12 does not follow the established thermodynamic hypothesis of amyloid
      formation. In this hypothesis, thermodynamically unstable proteins are more prone
      to amyloid formation. Here we show that within a thermal stability range, the
      most stable protein in this study is the most amyloidogenic protein. 

PMID- 26300553
TI  - Effect of seminal plasma proteins on the motile sperm subpopulations in ram
      ejaculates.
AB  - It has been proposed that seminal plasma proteins (SPP) support survival of ram
      spermatozoa, exerting a dual effect, both capacitating and decapacitating. In
      this study, changes in motility patterns of ram spermatozoa capacitated in the
      presence of epidermal growth factor (EGF) were evaluated. Clustering procedures
      were used to determine the presence of sperm subpopulations with specific motion
      characteristics. Four sperm subpopulations (SP) were defined after the
      application of a principal component analysis procedure. Progressive spermatozoa
      with high straightness (STR) were found in SP1, reflected in the high linearity
      (LIN) and STR values and low amplitude of lateral head movement (ALH; rapid, non
      hyperactivated spermatozoa). SP2 spermatozoa seemed to be starting to acquire
      hyperactivated motility, while the SP3 group consisted of rapid, hyperactivated
      spermatozoa. SP4 showed less-vigorous spermatozoa, with non-linear motility. The
      addition of SPP before in vitro capacitation with EGF induced a decrease in SP1
      and an increase in SP3. However, a reduction in the chlortetracycline-capacitated
      sperm rate and protein tyrosine phosphorylation was found, which corroborates
      with the hypothesis that the SPP protective effect on spermatozoa is related to
      their decapacitating role. These findings allow us to deduce that ram spermatozoa
      are able to undergo capacitation with no hyperactivation and that SPP are able to
      induce hyperactivation in spermatozoa but maintain them in a decapacitated state.

PMID- 26300555
TI  - Are religiousness and death attitudes associated with the wish to die in older
      people?
AB  - BACKGROUND: A wish to die is common in older persons and is associated with
      increased mortality. Several risk factors have been identified, but the
      association between religiousness and a wish to die in older adults has been
      underexplored, and the association between death attitudes and the presence of a
      wish to die has not been investigated yet. The aim of this study is to explore
      the relationship between religiousness and death attitudes on the one hand and
      wish to die on the other hand, adjusting for clinical factors such as the
      presence of depression or somatic disorder. METHODS: The sample comprised 113
      older inpatients (from a psychiatric and somatic ward) with a mean age of 74
      years. Psychiatric diagnoses were assessed by the Structured Clinical Interview
      for DSM-IV Disorders, and logistic regression analyses estimated the unique
      contribution of religiousness and death attitudes to the wish to die, controlling
      for socio-demographic variables, depressive disorder, and somatic symptoms.
      RESULTS: Both religiousness and death attitudes were associated with a wish to
      die in univariate models. Adding these variables in a multivariate logistic
      hierarchical model, death attitudes remained significant predictors but
      religiousness did not; 55% of the pseudovariance of the wish to die was explained
      by these variables, with an effective size of 0.89. Major depressive episode,
      somatic symptoms, Fear of Death, and Escape Acceptance were the most important
      predictors of the wish to die. CONCLUSIONS: This study suggests that how older
      adults perceive death partly determines whether they have a wish to die. There
      may be a clinical, patient-oriented benefit in discussing with older patients
      about how they perceive death, as this can play a role in the early detection
      (and prevention) of death or suicide ideation and associated behaviors in older
      adults.

PMID- 26300554
TI  - The Obese Brain--Effects of Bariatric Surgery on Energy Balance Neurocircuitry.
AB  - Obesity is a highly prevalent disease in the world and with a major impact on
      global health. While genetic components are also involved in its pathogenesis, in
      recent years, it has shown a critical role of the innate and adaptive immune cell
      response in many tissues triggered by excess of nutrients such as lipids and
      glucose. Free fatty acids and other nutrient-related signals induce damage such
      as insulin resistance in the peripheral tissues but also in the brain.
      Specifically in the hypothalamus, these metabolic signals can trigger significant
      changes in the control of energy balance. Recent studies have shown that
      saturated fat disrupts melanocortin signaling of hypothalamic neuronal subgroups
      pivotal to energy control. Bariatric surgery is a treatment option for obesity
      when other tools have failed, because it is more effective than pharmacotherapy
      concerning of weight loss itself and in improvement of obesity-related
      comorbidities. Here, we review the mechanisms by which Roux-en Y gastric bypass
      (RYGB) can change peripheral signals that modulate melanocortin circuits involved
      in the regulation of energy balance.

PMID- 26300556
TI  - National health insurance policy in Nepal: challenges for implementation.
AB  - The health system in Nepal is characterized by a wide network of health
      facilities and community workers and volunteers. Nepal's Interim Constitution of
      2007 addresses health as a fundamental right, stating that every citizen has the
      right to basic health services free of cost. But the reality is a far cry. Only
      61.8% of the Nepalese households have access to health facilities within 30 min,
      with significant urban (85.9%) and rural (59%) discrepancy. Addressing barriers
      to health services needs urgent interventions at the population level. Recently
      (February 2015), the Government of Nepal formed a Social Health Security
      Development Committee as a legal framework to start implementing a social health
      security scheme (SHS) after the National Health Insurance Policy came out in
      2013. The program has aimed to increase the access of health services to the poor
      and the marginalized, and people in hard to reach areas of the country, though
      challenges remain with financing. Several aspects should be considered in design,
      learning from earlier community-based health insurance schemes that suffered from
      low enrollment and retention of members as well as from a pro-rich bias.
      Mechanisms should be built for monitoring unfair pricing and unaffordable
      copayments, and an overall benefit package be crafted to include coverage of
      major health services including non-communicable diseases. Regulations should
      include such issues as accreditation mechanisms for private providers. Health
      system strengthening should move along with the roll-out of SHS. Improving the
      efficiency of hospital, motivating the health workers, and using appropriate
      technology can improve the quality of health services. Also, as currently a
      constitution drafting is being finalized, careful planning and deliberation is
      necessary about what insurance structure may suit the proposed future federal
      structure in Nepal. 

PMID- 26300558
TI  - The effect of pre-analytical treatment on the results of stoichiometric
      measurements in invertebrates.
AB  - Growing interest in the application of stoichiometric approaches to community
      ecology has resulted in an increasing number of studies examining invertebrate
      body composition. Our experiments demonstrate various sources of possible error
      related to the use of pre-analytical procedures. We examined the effects of
      different preservatives (ethanol and formaldehyde) used in pitfall traps, time of
      preservation (2 weeks or 3 days) and drying method (vacuum drying at 50  degrees
      C and freeze-drying) on the determination of body composition in invertebrates
      representing taxa often used in such studies: earthworms and five species of
      insects (adults or larvae). The contents of C, N, S, P, Fe, Zn, Cu, Mn, Ca, Mg
      and K in each animal were measured. The use of solvents (ethanol or formaldehyde)
      in pitfall traps and for preservation significantly affects the body composition
      and stoichiometry of earthworms, even during short exposure times. Insects (both
      adults and larvae) were affected only during a 2-week exposure; 3 days of
      exposure did not significantly change their chemical composition. Vacuum-oven
      drying of animals at 50  degrees C does not affect their body composition
      relative to freeze-drying.

PMID- 26300557
TI  - Patterns of youth injury: a comparison across the northern territories and other
      parts of Canada.
AB  - BACKGROUND: Injury is the leading cause of death for young people in Canada. For
      those living in the northern territories (Yukon, Nunavut, and the Northwest
      Territories), injury represents an even greater problem, with higher rates of
      injury for people of all ages in northern areas compared with the rest of Canada;
      however, no such comparative studies have focussed specifically on non-fatal
      injury in youth. OBJECTIVES: To profile and examine injuries and their potential
      causes among youth in the northern territories as compared with other parts of
      Canada. DESIGN: Cross-sectional data from the 2009/2010 Health Behaviour in
      School-aged Children survey (youth aged 11-15 years) were examined for the
      Canadian northern territories and the provinces (n=26,078). Individual survey
      records were linked to community-level data to profile injuries and then study
      possible determinants via multilevel regression modelling. RESULTS: The
      prevalence of injury reported by youth was similar in northern populations and
      other parts of Canada. There were some minimal differences by injury type:
      northern youth experienced a greater percentage of neighbourhood (p<0.001) and
      fighting (p=0.02) injuries; youth in the Canadian provinces had a greater
      proportion of sport-related injuries (p=0.01). Among northern youth, female sex
      (RR=0.87, 95% CI 0.81-0.94), average (RR=0.88, 95% CI 0.80-0.97) or above-average
      affluence (RR=0.84, 95% CI 0.76-0.91), not being drunk in the past 12 months
      (RR=0.77, 95% CI 0.69-0.85), not riding an all-terrain vehicle (RR=0.81, 95% CI
      0.68-0.97) and not having permanent road access (RR=0.89, 95% CI 0.80-0.98) were
      protective against injury; sport participation increased risk (RR=1.45, 95% CI
      1.33-1.59). CONCLUSIONS: Patterns of injury were similar across youth from the
      North and other parts of Canada. Given previous research, this was unexpected.
      When implementing injury prevention initiatives, individual and community-level
      risk factors are essential to understand; however, specific positive safety
      assets that might exist in different community contexts must also be considered.

PMID- 26300559
TI  - The sight of an adult brood parasite near the nest is an insufficient cue for a
      honeyguide host to reject foreign eggs.
AB  - Hosts of brood-parasitic birds typically evolve anti-parasitism defences,
      including mobbing of parasitic intruders at the nest and the ability to recognize
      and reject foreign eggs from their clutches. The Greater Honeyguide Indicator
      indicator is a virulent brood parasite that punctures host eggs and kills host
      young, and accordingly, a common host, the Little Bee-eater Merops pusillus
      frequently rejects entire clutches that have been parasitized. We predicted that
      given the high costs of accidentally rejecting an entire clutch, and that the
      experimental addition of a foreign egg is insufficient to induce this defence,
      Bee-eaters require the sight of an adult parasite near the nest as an additional
      cue for parasitism before they reject a clutch. We found that many Little Bee
      eater parents mobbed Greater Honeyguide dummies while ignoring barbet control
      dummies, showing that they recognized them as a threat. Surprisingly, however,
      neither a dummy Honeyguide nor the presence of a foreign egg, either separately
      or in combination, was sufficient to stimulate egg rejection.

PMID- 26300560
TI  - Implementation of Protocols To Enable Doctoral Training in Physical and
      Computational Chemistry of a Blind Graduate Student.
AB  - There exists a sparse representation of blind and low-vision students in science,
      technology, engineering and mathematics (STEM) fields. This is due in part to
      these individuals being discouraged from pursuing STEM degrees as well as a lack
      of appropriate adaptive resources in upper level STEM courses and research. Mona
      Minkara is a rising fifth year graduate student in computational chemistry at the
      University of Florida. She is also blind. This account presents efforts conducted
      by an expansive team of university and student personnel in conjunction with Mona
      to adapt different portions of the graduate student curriculum to meet Mona's
      needs. The most important consideration is prior preparation of materials to
      assist with coursework and cumulative exams. Herein we present an account of the
      first four years of Mona's graduate experience hoping this will assist in the
      development of protocols for future blind and low-vision graduate students in
      computational chemistry.

PMID- 26300561
TI  - Stationary Anonymous Sequential Games with Undiscounted Rewards.
AB  - Stationary anonymous sequential games with undiscounted rewards are a special
      class of games that combine features from both population games (infinitely many
      players) with stochastic games. We extend the theory for these games to the cases
      of total expected reward as well as to the expected average reward. We show that
      in the anonymous sequential game equilibria correspond to the limits of those of
      related finite population games as the number of players grows to infinity. We
      provide examples to illustrate our results.

PMID- 26300562
TI  - Affording introspection: an alternative model of inner awareness.
AB  - The ubiquity of inner awareness thesis (UIA) states that all conscious states of
      normal adult humans are characterised by an inner awareness of that very state.
      UIA-Backers support this thesis while UIA-Skeptics reject it. At the heart of
      their dispute is a recalcitrant phenomenological disagreement. UIA-Backers claim
      that phenomenological investigation reveals 'peripheral inner awareness' (or 'pre
      reflective self-consciousness') to be a constant presence in their non
      introspective experiences. UIA-Skeptics deny that their non-introspective
      experiences are characterised by inner awareness, and maintain that inner
      awareness is only gained when they explicitly introspect. Each camp has put
      forward a range of arguments designed to resolve this dispute, but I argue that
      none of these arguments has genuine dialectical purchase. This leads me to
      develop a compromise position that trades on the contribution that affordances
      can make to our phenomenology. According to the Affordance Model of inner
      awareness, all conscious states of normal adult humans are characterised by an
      affordance of introspectability. In line with the UIA-Skeptic, non-introspective
      experiences are not characterised by inner awareness. But against the traditional
      UIASkeptic, non-introspective experiences are characterised by an awareness of
      the opportunity for introspection. On this view, our capacity to gain inner
      awareness of our current experience is a ubiquitous feature of our phenomenology.
      I show how the Affordance Model respects the driving phenomenological intuitions
      of both the UIA-Backers and the traditional UIA-Skeptics, and suggest that it is
      able to explain why neither camp achieves an accurate description of how inner
      awareness figures in their phenomenology.

PMID- 26300563
TI  - Tidal effects on stratospheric temperature series derived from successive
      advanced microwave sounding units.
AB  - Stratospheric temperature series derived from the Advanced Microwave Sounding
      Unit (AMSU) on board successive NOAA satellites reveal, during periods of
      overlap, some bias and drifts. Part of the reason for these discrepancies could
      be atmospheric tides as the orbits of these satellites drifted, inducing large
      changes in the actual times of measurement. NOAA 15 and 16, which exhibit a long
      period of overlap, allow deriving diurnal tides that can correct such temperature
      drifts. The characteristics of the derived diurnal tides during summer periods is
      in good agreement with those calculated with the Global Scale Wave Model,
      indicating that most of the observed drifts are likely due to the atmospheric
      tides. Cooling can be biased by a factor of 2, if times of measurement are not
      considered. When diurnal tides are considered, trends derived from temperature
      lidar series are in good agreement with AMSU series. Future adjustments of
      temperature time series based on successive AMSU instruments will require
      considering corrections associated with the local times of measurement.

PMID- 26300564
TI  - Polar vortices on Earth and Mars: A comparative study of the climatology and
      variability from reanalyses.
AB  - Polar vortices on Mars provide case-studies to aid understanding of geophysical
      vortex dynamics and may help to resolve long-standing issues regarding polar
      vortices on Earth. Due to the recent development of the first publicly available
      Martian reanalysis dataset (MACDA), for the first time we are able to
      characterise thoroughly the structure and evolution of the Martian polar
      vortices, and hence perform a systematic comparison with the polar vortices on
      Earth. The winter atmospheric circulations of the two planets are compared, with
      a specific focus on the structure and evolution of the polar vortices. The
      Martian residual meridional overturning circulation is found to be very similar
      to the stratospheric residual circulation on Earth during winter. While on Earth
      this residual circulation is very different from the Eulerian circulation, on
      Mars it is found to be very similar. Unlike on Earth, it is found that the
      Martian polar vortices are annular, and that the Northern Hemisphere vortex is
      far stronger than its southern counterpart. While winter hemisphere differences
      in vortex strength are also reported on Earth, the contrast is not as large.
      Distinctions between the two planets are also apparent in terms of the
      climatological vertical structure of the vortices, in that the Martian polar
      vortices are observed to decrease in size at higher altitudes, whereas on Earth
      the opposite is observed. Finally, it is found that the Martian vortices are less
      variable through the winter than on Earth, especially in terms of the vortex
      geometry. During one particular major regional dust storm on Mars (Martian year
      26), an equatorward displacement of the vortex is observed, sharing some
      qualitative characteristics of sudden stratospheric warmings on Earth.

PMID- 26300565
TI  - Applications of Ring Closing Metathesis. Total Synthesis of (+/-)
      Pseudotabersonine.
AB  - A novel approach to the Aspidosperma family of alkaloids was developed and
      applied to a concise total synthesis of (+/-)-pseudotabersonine that was
      accomplished in 11 steps. Key transformations include a stepwise variant of a
      Mannich-like multicomponent assembly process, a double ring-closing metathesis
      sequence, and a one-pot deprotection/cyclization reaction.

PMID- 26300566
TI  - Biographical Narratives of Encounter: The Significance of Mobility and
      Emplacement in Shaping Attitudes towards Difference.
AB  - This paper is located within work in urban studies about the significance of
      contact with difference as a means for reducing prejudice and achieving social
      change. Recent approaches, influenced by theories of affect, have emphasised non
      conscious everyday negotiations of difference in the city. In this paper it is
      argued that such approaches lose sight of the significance of the subject: of the
      reflective judgements of 'others' made by individuals; of our ability to make
      decisions around the control of our feelings and identifications; and of the
      significance of personal pasts and collective histories in shaping the ways we
      perceive and react to encounters. Rather, this paper uses a biographical approach
      focusing on interviewees' narratives of encounter. Through its attention to
      processes of mobility and emplacement, it contributes to debates about when
      contact with difference matters by highlighting the importance of everyday social
      normativities in the production of moral dispositions.

PMID- 26300567
TI  - Photocatalytic Hydrogen Production using Polymeric Carbon Nitride with a
      Hydrogenase and a Bioinspired Synthetic Ni Catalyst.
AB  - Solar-light-driven H2 production in water with a [NiFeSe]-hydrogenase (H2ase) and
      a bioinspired synthetic nickel catalyst (NiP) in combination with a heptazine
      carbon nitride polymer, melon (CNx), is reported. The semibiological and purely
      synthetic systems show catalytic activity during solar light irradiation with
      turnover numbers (TONs) of more than 50 000 mol H2 (mol H2ase)-1 and
      approximately 155 mol H2 (mol NiP)-1 in redox-mediator-free aqueous solution at
      pH 6 and 4.5, respectively. Both systems maintained a reduced photoactivity under
      UV-free solar light irradiation (lambda>420 nm).

PMID- 26300568
TI  - Macrodiolide Formation by the Thioesterase of a Modular Polyketide Synthase.
AB  - Elaiophylin is an unusual C2-symmetric antibiotic macrodiolide produced on a
      bacterial modular polyketide synthase assembly line. To probe the mechanism and
      selectivity of diolide formation, we sought to reconstitute ring formation in
      vitro by using a non-natural substrate. Incubation of recombinant elaiophylin
      thioesterase/cyclase with a synthetic pentaketide analogue of the presumed
      monomeric polyketide precursor of elaiophylin, specifically its N
      acetylcysteamine thioester, produced a novel 16-membered C2-symmetric
      macrodiolide. A linear dimeric thioester is an intermediate in ring formation,
      which indicates iterative use of the thioesterase active site in ligation and
      subsequent cyclization. Furthermore, the elaiophylin thioesterase acts on a
      mixture of pentaketide and tetraketide thioesters to give both the symmetric
      decaketide diolide and the novel asymmetric hybrid nonaketide diolide. Such
      thioesterases have potential as tools for the in vitro construction of novel
      diolides.

PMID- 26300569
TI  - Dual Binding of an Antibody and a Small Molecule Increases the Stability of TERRA
      G-Quadruplex.
AB  - In investigating the binding interactions between the human telomeric RNA (TERRA)
      G-quadruplex (GQ) and its ligands, it was found that the small molecule
      carboxypyridostatin (cPDS) and the GQ-selective antibody BG4 simultaneously bind
      the TERRA GQ. We previously showed that the overall binding affinity of BG4 for
      RNA GQs is not significantly affected in the presence of cPDS. However, single
      molecule mechanical unfolding experiments revealed a population (48 %) with
      substantially increased mechanical and thermodynamic stability. Force-jump
      kinetic investigations suggested competitive binding of cPDS and BG4 to the TERRA
      GQ. Following this, the two bound ligands slowly rearrange, thereby leading to
      the minor population with increased stability. Given the relevance of G
      quadruplexes in the regulation of biological processes, we anticipate that the
      unprecedented conformational rearrangement observed in the TERRA-GQ-ligand
      complex may inspire new strategies for the selective stabilization of G
      quadruplexes in cells.

PMID- 26300570
TI  - Application of a Persistent Dissolved-phase Reactive Treatment Zone for
      Mitigation of Mass Discharge from Sources Located in Lower-Permeability
      Sediments.
AB  - The purpose of this study is to examine the development and effectiveness of a
      persistent dissolved-phase treatment zone, created by injecting potassium
      permanganate solution, for mitigating discharge of contaminant from a source zone
      located in a relatively deep, low-permeability formation. A localized 1,1
      dichloroethene (DCE) source zone comprising dissolved- and sorbed-phase mass is
      present in lower permeability strata adjacent to a sand/gravel unit in a section
      of the Tucson International Airport Area (TIAA) Superfund Site. The results of
      bench-scale studies conducted using core material collected from boreholes
      drilled at the site indicated that natural oxidant demand was low, which would
      promote permanganate persistence. The reactive zone was created by injecting a
      permanganate solution into multiple wells screened across the interface between
      the lower-permeability and higher-permeability units. The site has been monitored
      for nine years to characterize the spatial distribution of DCE and permanganate.
      Permanganate continues to persist at the site, and a substantial and sustained
      decrease in DCE concentrations in groundwater has occurred after the permanganate
      injection.. These results demonstrate successful creation of a long-term,
      dissolved-phase reactive-treatment zone that reduced mass discharge from the
      source. This project illustrates the application of in-situ chemical oxidation as
      a persistent dissolved-phase reactive-treatment system for lower-permeability
      source zones, which appears to effectively mitigate persistent mass discharge
      into groundwater.

PMID- 26300572
TI  - The Effect on Fertility of the 2003-2011 War in Iraq.
AB  - This article provides the first detailed account of recent fertility trends in
      Iraq, with a particular focus on the changes resulting from the 2003-2011 war and
      the factors underlying them. The study is based on retrospective birth history
      data from the 2006 and 2011 Iraq Multiple Indicator Cluster Surveys (I-MICS).
      Estimates from the two surveys indicate that total fertility remained stable from
      1997 to 2010, at about 4.5 children per woman. However, examination of the age
      patterns of fertility reveals an abrupt shift in the timing of births, with
      adolescent fertility rising by over 30 percent soon after the onset of the war. A
      decomposition analysis shows that the rise in early childbearing is due to an
      increased prevalence of early marriage among less-educated women. The prevalence
      of early marriage and childbearing among women with secondary or higher education
      is relatively low and has not increased after 2003.

PMID- 26300571
TI  - Cometabolic Degradation of Naproxen by Planococcus sp. Strain S5.
AB  - Naproxen is a non-steroidal anti-inflammatory drug frequently detected in the
      influent and effluent of sewage treatment plants. The Gram-positive strain
      Planococcus sp. S5 was able to remove approximately 30 % of naproxen after 35
      days of incubation in monosubstrate culture. Under cometabolic conditions, with
      glucose or phenol as a growth substrate, the degradation efficiency of S5
      increased. During 35 days of incubation, 75.14 +/- 1.71 % and 86.27 +/- 2.09 % of
      naproxen was degraded in the presence of glucose and phenol, respectively. The
      highest rate of naproxen degradation observed in the presence of phenol may be
      connected with the fact that phenol is known to induce enzymes responsible for
      aromatic ring cleavage. The activity of phenol monooxygenase, naphthalene
      monooxygenase, and hydroxyquinol 1,2-dioxygenase was indicated in Planococcus sp.
      S5 culture with glucose or phenol as a growth substrate. It is suggested that
      these enzymes may be engaged in naproxen degradation.

PMID- 26300573
TI  - Centrifuge modeling of rocking-isolated inelastic RC bridge piers.
AB  - Experimental proof is provided of an unconventional seismic design concept, which
      is based on deliberately underdesigning shallow foundations to promote intense
      rocking oscillations and thereby to dramatically improve the seismic resilience
      of structures. Termed rocking isolation, this new seismic design philosophy is
      investigated through a series of dynamic centrifuge experiments on properly
      scaled models of a modern reinforced concrete (RC) bridge pier. The experimental
      method reproduces the nonlinear and inelastic response of both the soil-footing
      interface and the structure. To this end, a novel scale model RC (1:50 scale)
      that simulates reasonably well the elastic response and the failure of prototype
      RC elements is utilized, along with realistic representation of the soil behavior
      in a geotechnical centrifuge. A variety of seismic ground motions are considered
      as excitations. They result in consistent demonstrably beneficial performance of
      the rocking-isolated pier in comparison with the one designed conventionally.
      Seismic demand is reduced in terms of both inertial load and deck drift.
      Furthermore, foundation uplifting has a self-centering potential, whereas soil
      yielding is shown to provide a particularly effective energy dissipation
      mechanism, exhibiting significant resistance to cumulative damage. Thanks to such
      mechanisms, the rocking pier survived, with no signs of structural distress, a
      deleterious sequence of seismic motions that caused collapse of the
      conventionally designed pier.

PMID- 26300575
TI  - Certification of Total Arsenic in Blood and Urine Standard Reference Materials by
      Radiochemical Neutron Activation Analysis and Inductively Coupled Plasma - Mass
      Spectrometry.
AB  - A newly developed procedure for determination of arsenic by radiochemical neutron
      activation analysis (RNAA) was used to measure arsenic at four levels in SRM 955c
      Toxic Elements in Caprine Blood and at two levels in SRM 2668 Toxic Elements in
      Frozen Human Urine for the purpose of providing mass concentration values for
      certification. Samples were freeze-dried prior to analysis followed by neutron
      irradiation for 3 h at a fluence rate of 1*1014cm-2s-1. After sample dissolution
      in perchloric and nitric acids, arsenic was separated from the matrix by
      extraction into zinc diethyldithiocarbamate in chloroform, and 76As quantified by
      gamma-ray spectroscopy. Differences in chemical yield and counting geometry
      between samples and standards were monitored by measuring the count rate of a
      77As tracer added before sample dissolution. RNAA results were combined with
      inductively coupled plasma - mass spectrometry (ICP-MS) values from NIST and
      collaborating laboratories to provide certified values of (10.81 +/- 0.54) MUg/kg
      and (213.1 +/- 0.73) MUg/kg for SRM 2668 Levels I and II, and certified values of
      (21.66 +/- 0.73) MUg/kg, (52.7 +/- 1.1) MUg/kg, and (78.8 +/- 4.9) MUg/kg for SRM
      955c Levels 2, 3, and 4 respectively. Because of discrepancies between values
      obtained by different methods for SRM 955c Level 1, an information value of < 5
      MUg/kg was assigned for this material.

PMID- 26300574
TI  - Potential of legume-based grassland-livestock systems in Europe: a review.
AB  - European grassland-based livestock production systems face the challenge of
      producing more meat and milk to meet increasing world demands and to achieve this
      using fewer resources. Legumes offer great potential for achieving these
      objectives. They have numerous features that can act together at different stages
      in the soil-plant-animal-atmosphere system, and these are most effective in mixed
      swards with a legume proportion of 30-50%. The resulting benefits include reduced
      dependence on fossil energy and industrial N-fertilizer, lower quantities of
      harmful emissions to the environment (greenhouse gases and nitrate), lower
      production costs, higher productivity and increased protein self-sufficiency.
      Some legume species offer opportunities for improving animal health with less
      medication, due to the presence of bioactive secondary metabolites. In addition,
      legumes may offer an adaptation option to rising atmospheric CO2 concentrations
      and climate change. Legumes generate these benefits at the level of the managed
      land-area unit and also at the level of the final product unit. However, legumes
      suffer from some limitations, and suggestions are made for future research to
      exploit more fully the opportunities that legumes can offer. In conclusion, the
      development of legume-based grassland-livestock systems undoubtedly constitutes
      one of the pillars for more sustainable and competitive ruminant production
      systems, and it can be expected that forage legumes will become more important in
      the future.

PMID- 26300576
TI  - One, four or 100 genera? A new classification of the cone snails.
AB  - We present a new classification for the genus Conus sensu lato (family Conidae),
      based on molecular phylogenetic analyses of 329 species. This classification
      departs from both the traditional classification in only one genus and from a
      recently proposed shell- and radula-based classification scheme that separates
      members of this group into five families and 115 genera. Roughly 140 genus-group
      names are available for Recent cone snails. We propose to place all cone snails
      within a single family (Conidae) containing four genera-Conus, Conasprella,
      Profundiconus and Californiconus (with Conus alone encompassing about 85% of
      known species)-based on the clear separation of cone snails into four distinct
      and well-supported groups/lineages in molecular phylogenetic analyses. Within
      Conus and Conasprella, we recognize 57 and 11 subgenera, respectively, that
      represent well-supported subgroupings within these genera, which we interpret as
      evidence of intrageneric distinctiveness. We allocate the 803 Recent species of
      Conidae listed as valid in the World Register of Marine Species into these four
      genera and 71 subgenera, with an estimate of the confidence for placement of
      species in these taxonomic categories based on whether molecular or radula and/or
      shell data were used in these determinations. Our proposed classification
      effectively departs from previous schemes by (1) limiting the number of accepted
      genera, (2) retaining the majority of species within the genus Conus and (3)
      assigning members of these genera to species groups/subgenera to enable the
      effective communication of these groups, all of which we hope will encourage
      acceptance of this scheme.

PMID- 26300577
TI  - Dilatant shear band formation and diagenesis in calcareous, arkosic sandstones,
      Vienna Basin (Austria).
AB  - The present study examines deformation bands in calcareous arkosic sands. The
      investigated units can be considered as an equivalent to the Matzen field in the
      Vienna Basin (Austria), which is one of the most productive oil reservoirs in
      central Europe. The outcrop exposes carbonate-free and carbonatic sediments of
      Badenian age separated by a normal fault. Carbonatic sediments in the hanging
      wall of the normal fault develop dilation bands with minor shear displacements (<
      2 mm), whereas carbonate-free sediments in the footwall develop cataclastic shear
      bands with up to 70 cm displacement. The cataclastic shear bands show a
      permeability reduction up to 3 orders of magnitude and strong baffling effects in
      the vadose zone. Carbonatic dilation bands show a permeability reduction of 1-2
      orders of magnitude and no baffling structures. We distinguished two types of
      deformation bands in the carbonatic units, which differ in deformation
      mechanisms, distribution and composition. Full-cemented bands form as dilation
      bands with an intense syn-kinematic calcite cementation, whereas the younger
      loose-cemented bands are dilatant shear bands cemented by patchy calcite and clay
      minerals. All analyzed bands are characterized by a porosity and permeability
      reduction caused by grain fracturing and cementation. The changed petrophysical
      properties and especially the porosity evolution are closely related to
      diagenetic processes driven by varying pore fluids in different diagenetic
      environments. The deformation band evolution and sealing capacity is controlled
      by the initial host rock composition.

PMID- 26300578
TI  - Cone-Beam CT of Traumatic Brain Injury Using Statistical Reconstruction with a
      Post-Artifact-Correction Noise Model.
AB  - Traumatic brain injury (TBI) is a major cause of death and disability. The
      current front-line imaging modality for TBI detection is CT, which reliably
      detects intracranial hemorrhage (fresh blood contrast 30-50 HU, size down to 1
      mm) in non-contrast-enhanced exams. Compared to CT, flat-panel detector (FPD)
      cone-beam CT (CBCT) systems offer lower cost, greater portability, and smaller
      footprint suitable for point-of-care deployment. We are developing FPD-CBCT to
      facilitate TBI detection at the point-of-care such as in emergent, ambulance,
      sports, and military applications. However, current FPD-CBCT systems generally
      face challenges in low-contrast, soft-tissue imaging. Model-based reconstruction
      can improve image quality in soft-tissue imaging compared to conventional
      filtered backprojection (FBP) by leveraging high-fidelity forward model and
      sophisticated regularization. In FPD-CBCT TBI imaging, measurement noise
      characteristics undergo substantial change following artifact correction,
      resulting in non-negligible noise amplification. In this work, we extend the
      penalized weighted least-squares (PWLS) image reconstruction to include the two
      dominant artifact corrections (scatter and beam hardening) in FPD-CBCT TBI
      imaging by correctly modeling the variance change following each correction.
      Experiments were performed on a CBCT test-bench using an anthropomorphic phantom
      emulating intra-parenchymal hemorrhage in acute TBI, and the proposed method
      demonstrated an improvement in blood-brain contrast-to-noise ratio (CNR = 14.2)
      compared to FBP (CNR = 9.6) and PWLS using conventional weights (CNR = 11.6) at
      fixed spatial resolution (1 mm edge-spread width at the target contrast). The
      results support the hypothesis that FPD-CBCT can fulfill the image quality
      requirements for reliable TBI detection, using high-fidelity artifact correction
      and statistical reconstruction with accurate post-artifact-correction noise
      models.

PMID- 26300579
TI  - Chemokine Coreceptor-2 Gene Polymorphisms among HIV-1 Infected Individuals in
      Kenya.
AB  - Chemokine Coreceptor-2 (CCR2) is an entry coreceptor for HIV-1. A mutation in the
      coding gene for this coreceptor, CCR2-64I, has been shown to be an important
      factor for delaying disease progression. In Kenya no studies have been done to
      determine the status of CCR2 gene polymorphisms among HIV-1 infected individuals.
      To determine the existence and distribution of CCR2 gene mutations and identify
      polymorphic groups of the coreceptor gene in the population, a cross-sectional
      study was conducted to analyze the differences in allelic frequencies of CCR2-64I
      among HIV-1 seropositive individuals. Blood samples were collected from HIV/AIDS
      screening centers and analyzed for the presence of CCR2-64I using restriction
      fragment length polymorphism (RFLP). One hundred and eighteen samples collected
      from different regions of the country were genotyped for the CCR2-64I mutation.
      Of these, 4 (3.4%) were homozygous mutants (I/I) and 21 (17.8%) were heterozygous
      (V/I). Ninety-three subjects (78.8%) were wild type (V/V). With the search for a
      preventive/therapeutic HIV vaccine elusive, the presence of CCR-2 gene
      polymorphisms that delay disease progression and prolong the lives of the
      infected in the Kenyan population may contribute to the growing evidence that
      host genetic factors are important in predicting susceptibility to HIV-1
      infection. 

PMID- 26300580
TI  - Civic Competence of Youth in Europe: Measuring Cross National Variation Through
      the Creation of a Composite Indicator.
AB  - This article develops a composite indicator to monitor the levels of civic
      competence of young people in Europe using the IEA ICCS 2009 study. The
      measurement model combines the traditions in Europe of liberal, civic republican
      and critical/cosmopolitan models of citizenship. The results indicate that social
      justice values and citizenship knowledge and skills of students are facilitated
      within the Nordic system that combines a stable democracy and economic prosperity
      with a democratically based education systems in which teachers prioritise
      promoting autonomous critical thinking in citizenship education. In contrast,
      medium term democracies with civic republican tradition, such as Italy and Greece
      gain more positive results on citizenship values and participatory attitudes.
      This is also the case for some recent former communist countries that retain
      ethnic notions of citizenship. In a final step we go on to argue that the Nordic
      teachers' priority on developing critical and autonomous citizens perhaps
      facilitates 14 years olds qualities of cognition on citizenship and the values of
      equality but may not be the most fruitful approach to enhance participatory
      attitudes or concepts of a good citizen which may be better supported by the
      Italian teachers' priority on civic responsibility.

PMID- 26300581
TI  - Culture and Happiness.
AB  - Culture is an important factor affecting happiness. This paper examines the
      predictive power of cultural factors on the cross-country differences in
      happiness and explores how different dimensions of cultural indices differ in
      their effects on happiness. Our empirical results show that the global leadership
      and organizational behavior effectiveness nine culture indices are all
      significantly related with happiness. Out of these nine indices, power distance
      (PDI) and gender egalitarianism (GEI) play the most important and stable role in
      determining subjective well-being (SWB). We further examine the relative
      importance of the various variables in contributing to the R-squared of the
      regression. The results show that PDI is the most important, accounting for 50 %
      of the contributions to R-squared of all variables, or equalling the combined
      contributions of income, population density and four other traditional variables.
      The contribution of GEI is 37.1 %, also well surpassing other variables. Our
      results remain robust even taking account of the different data for culture and
      SWB.

PMID- 26300582
TI  - Earnings Quality Measures and Excess Returns.
AB  - This paper examines how commonly used earnings quality measures fulfill a key
      objective of financial reporting, i.e., improving decision usefulness for
      investors. We propose a stock-price-based measure for assessing the quality of
      earnings quality measures. We predict that firms with higher earnings quality
      will be less mispriced than other firms. Mispricing is measured by the difference
      of the mean absolute excess returns of portfolios formed on high and low values
      of a measure. We examine persistence, predictability, two measures of smoothness,
      abnormal accruals, accruals quality, earnings response coefficient and value
      relevance. For a large sample of US non-financial firms over the period 1988
      2007, we show that all measures except for smoothness are negatively associated
      with absolute excess returns, suggesting that smoothness is generally a favorable
      attribute of earnings. Accruals measures generate the largest spread in absolute
      excess returns, followed by smoothness and market-based measures. These results
      lend support to the widespread use of accruals measures as overall measures of
      earnings quality in the literature.

PMID- 26300583
TI  - Acoustic behavior of melon-headed whales varies on a diel cycle.
AB  - Many terrestrial and marine species have a diel activity pattern, and their
      acoustic signaling follows their current behavioral state. Whistles and
      echolocation clicks on long-term recordings produced by melon-headed whales
      (Peponocephala electra) at Palmyra Atoll indicated that these signals were used
      selectively during different phases of the day, strengthening the idea of
      nighttime foraging and daytime resting with afternoon socializing for this
      species. Spectral features of their echolocation clicks changed from day to
      night, shifting the median center frequency up. Additionally, click received
      levels increased with increasing ambient noise during both day and night. Ambient
      noise over a wide frequency band was on average higher at night. The diel
      adjustment of click features might be a reaction to acoustic masking caused by
      these nighttime sounds. Similar adaptations have been documented for numerous
      taxa in response to noise. Or it could be, unrelated, an increase in biosonar
      source levels and with it a shift in center frequency to enhance detection
      distances during foraging at night. Call modifications in intensity,
      directionality, frequency, and duration according to echolocation task are well
      established for bats. This finding indicates that melon-headed whales have
      flexibility in their acoustic behavior, and they collectively and repeatedly
      adapt their signals from day- to nighttime circumstances.

PMID- 26300584
TI  - Intersecting dilated convex polyhedra method for modeling complex particles in
      discrete element method.
AB  - This paper describes a new method for representing concave polyhedral particles
      in a discrete element method as unions of convex dilated polyhedra. This method
      offers an efficient way to simulate systems with a large number of (generally
      concave) polyhedral particles. The method also allows spheres, capsules, and
      dilated triangles to be combined with polyhedra using the same approach. The
      computational efficiency of the method is tested in two different simulation
      setups using different efficiency metrics for seven particle types: spheres,
      clusters of three spheres, clusters of four spheres, tetrahedra, cubes, unions of
      two octahedra (concave), and a model of a computer tomography scan of a lunar
      simulant GRC-3 particle. It is shown that the computational efficiency of the
      simulations degrades much slower than the increase in complexity of the particles
      in the system. The efficiency of the method is based on the time coherence of the
      system, and an efficient and robust distance computation method between polyhedra
      as particles never intersect for dilated particles.

PMID- 26300585
TI  - Application of a model for delivering occupational safety and health to smaller
      businesses: Case studies from the US.
AB  - Smaller firms are the majority in every industry in the US, and they endure a
      greater burden of occupational injuries, illnesses, and fatalities than larger
      firms. Smaller firms often lack the necessary resources for effective
      occupational safety and health activities, and many require external assistance
      with safety and health programming. Based on previous work by researchers in
      Europe and New Zealand, NIOSH researchers developed for occupational safety and
      health intervention in small businesses. This model was evaluated with several
      intermediary organizations. Four case studies which describe efforts to reach
      small businesses with occupational safety and health assistance include the
      following: trenching safety training for construction, basic compliance and
      hazard recognition for general industry, expanded safety and health training for
      restaurants, and fall prevention and respirator training for boat repair
      contractors. Successful efforts included participation by the initiator among the
      intermediaries' planning activities, alignment of small business needs with
      intermediary offerings, continued monitoring of intermediary activities by the
      initiator, and strong leadership for occupational safety and health among
      intermediaries. Common challenges were a lack of resources among intermediaries,
      lack of opportunities for in-person meetings between intermediaries and the
      initiator, and balancing the exchanges in the initiator-intermediary-small
      business relationships. The model offers some encouragement that initiator
      organizations can contribute to sustainable OSH assistance for small firms, but
      they must depend on intermediaries who have compatible interests in smaller
      businesses and they must work to understand the small business social system.

PMID- 26300586
TI  - Symptoms of Mental Health Problems: Children's and Adolescents' Understandings
      and Implications for Gender Differences in Help Seeking.
AB  - Amidst concerns that young people's mental health is deteriorating, it is
      important to explore their understandings of symptoms of mental health problems
      and beliefs around help seeking. Drawing on focus group data from Scottish school
      pupils, we demonstrate how they understood symptoms of mental health problems and
      how their characterisations of these symptoms as 'rare' and 'weird' informed
      participants' perceptions that peers, teachers and parents would respond to
      disclosure in stigmatising ways. Consequently, participants suggested that they
      would delay or avoid disclosing symptoms of mental health problems. We highlight
      subtle gender and age differences and outline implications for policy and
      practice.

PMID- 26300587
TI  - Purinergic Signalling in Immune System Regulation in Health and Disease.

PMID- 26300588
TI  - Binding of CXCL8/IL-8 to Mycobacterium tuberculosis Modulates the Innate Immune
      Response.
AB  - Interleukin-8 (IL-8) has been implicated in the pathogenesis of several human
      respiratory diseases, including tuberculosis (TB). Importantly and in direct
      relevance to the objectives of this report quite a few findings suggest that the
      presence of IL-8 may be beneficial for the host. IL-8 may aid with mounting an
      adequate response during infection with Mycobacterium tuberculosis (M. tb);
      however, the underlying mechanism remains largely unknown. The major goal of our
      study was to investigate the contribution of IL-8 to the inflammatory processes
      that are typically elicited in patients with TB. We have shown for the first time
      that IL-8 can directly bind to tubercle bacilli. We have also demonstrated that
      association of IL-8 with M. tb molecules leads to the augmentation of the ability
      of leukocytes (neutrophils and macrophages) to phagocyte and kill these bacilli.
      In addition, we have shown that significant amount of IL-8 present in the blood
      of TB patients associates with erythrocytes. Finally, we have noted that IL-8 is
      the major chemokine responsible for recruiting T lymphocytes (CD3(+), CD4(+), and
      CD8(+) T cells). In summary, our data suggest that the association of IL-8 with
      M. tb molecules may modify and possibly enhance the innate immune response in
      patients with TB. 

PMID- 26300589
TI  - Inhibition of Epithelial CC-Family Chemokine Synthesis by the Synthetic Chalcone
      DMPF-1 via Disruption of NF-kappaB Nuclear Translocation and Suppression of
      Experimental Asthma in Mice.
AB  - Asthma is associated with increased pulmonary inflammation and airway
      hyperresponsiveness. The interaction between airway epithelium and inflammatory
      mediators plays a key role in the pathogenesis of asthma. In vitro studies
      evaluated the inhibitory effects of 3-(2,5-dimethoxyphenyl)-1-(5-methylfuran-2
      yl)prop-2-en-1-one (DMPF-1), a synthetic chalcone analogue, upon inflammation in
      the A549 lung epithelial cell line. DMPF-1 selectively inhibited TNF-alpha
      stimulated CC chemokine secretion (RANTES, eotaxin-1, and MCP-1) without any
      effect upon CXC chemokine (GRO-alpha and IL-8) secretion. Western blot analysis
      further demonstrated that the inhibitory activity resulted from disruption of
      p65NF-kappaB nuclear translocation without any effects on the mitogen-activated
      protein kinase (MAPK) pathway. Treatment of ovalbumin-sensitized and ovalbumin
      challenged BALB/c mice with DMPF-1 (0.2-100 mg/kg) demonstrated significant
      reduction in the secretion and gene expression of CC chemokines (RANTES, eotaxin
      1, and MCP-1) and Th2 cytokines (IL-4, IL-5, and IL-13). Furthermore, DMPF-1
      treatment inhibited eosinophilia, goblet cell hyperplasia, peripheral blood total
      IgE, and airway hyperresponsiveness in ovalbumin-sensitized and ovalbumin
      challenged mice. In conclusion, these findings demonstrate the potential of DMPF
      1, a nonsteroidal compound, as an antiasthmatic agent for further pharmacological
      evaluation. 

PMID- 26300590
TI  - Microparticles That Form Immune Complexes as Modulatory Structures in Autoimmune
      Responses.
AB  - Microparticles (MPs) are induced during apoptosis, cell activation, and even
      "spontaneous" release. Initially MPs were considered to be inert cellular
      products with no biological function. However, an extensive research and
      functional characterization have shown that the molecular composition and the
      effects of MPs depend upon the cellular background and the mechanism inducing
      them. They possess a wide spectrum of biological effects on intercellular
      communication by transferring different molecules able to modulate other cells.
      MPs interact with their target cells through different mechanisms: membrane
      fusion, macropinocytosis, and receptor-mediated endocytosis. However, when MPs
      remain in the extracellular milieu, they undergo modifications such as
      citrullination, glycosylation, and partial proteolysis, among others, becoming a
      source of neoantigens. In rheumatoid arthritis (RA) and systemic lupus
      erythematosus (SLE), reports indicated elevated levels of MPs with different
      composition, content, and effects compared with those isolated from healthy
      individuals. MPs can also form immune complexes amplifying the proinflammatory
      response and tissue damage. Their early detection and characterization could
      facilitate an appropriate diagnosis optimizing the pharmacological strategies, in
      different diseases including cancer, infection, and autoimmunity. This review
      focuses on the current knowledge about MPs and their involvement in the
      immunopathogenesis of SLE and RA. 

PMID- 26300591
TI  - Selected Aspects in the Pathogenesis of Autoimmune Diseases.
AB  - Autoimmune processes can be found in physiological circumstances. However, they
      are quenched with properly functioning regulatory mechanisms and do not evolve
      into full-blown autoimmune diseases. Once developed, autoimmune diseases are
      characterized by signature clinical features, accompanied by sustained cellular
      and/or humoral immunological abnormalities. Genetic, environmental, and hormonal
      defects, as well as a quantitative and qualitative impairment of immunoregulatory
      functions, have been shown in parallel to the relative dominance of
      proinflammatory Th17 cells in many of these diseases. In this review we focus on
      the derailed balance between regulatory and Th17 cells in the pathogenesis of
      autoimmune diseases. Additionally, we depict a cytokine imbalance, which gives
      rise to a biased T-cell homeostasis. The assessment of Th17/Treg-cell ratio and
      the simultaneous quantitation of cytokines, may give a useful diagnostic tool in
      autoimmune diseases. We also depict the multifaceted role of dendritic cells,
      serving as antigen presenting cells, contributing to the development of the
      pathognomonic cytokine signature and promote cellular and humoral autoimmune
      responses. Finally we describe the function and role of extracellular vesicles in
      particular autoimmune diseases. Targeting these key players of disease
      progression in patients with autoimmune diseases by immunomodulating therapy may
      be beneficial in future therapeutic strategies. 

PMID- 26300592
TI  - Follicular Helper CD4+ T Cells in Human Neuroautoimmune Diseases and Their Animal
      Models.
AB  - Follicular helper CD4(+) T (TFH) cells play a fundamental role in humoral
      immunity deriving from their ability to provide help for germinal center (GC)
      formation, B cell differentiation into plasma cells and memory cells, and
      antibody production in secondary lymphoid tissues. TFH cells can be identified by
      a combination of markers, including the chemokine receptor CXCR5, costimulatory
      molecules ICOS and PD-1, transcription repressor Bcl-6, and cytokine IL-21. It is
      difficult and impossible to get access to secondary lymphoid tissues in humans,
      so studies are usually performed with human peripheral blood samples as
      circulating counterparts of tissue TFH cells. A balance of TFH cell generation
      and function is critical for protective antibody response, whereas overactivation
      of TFH cells or overexpression of TFH-associated molecules may result in
      autoimmune diseases. Emerging data have shown that TFH cells and TFH-associated
      molecules may be involved in the pathogenesis of neuroautoimmune diseases
      including multiple sclerosis (MS), neuromyelitis optica (NMO)/neuromyelitis
      optica spectrum disorders (NMOSD), and myasthenia gravis (MG). This review
      summarizes the features of TFH cells, including their development, function, and
      roles as well as TFH-associated molecules in neuroautoimmune diseases and their
      animal models. 

PMID- 26300593
TI  - Bleomycin-Treated Chimeric Thy1-Deficient Mice with Thy1-Deficient Myofibroblasts
      and Thy-Positive Lymphocytes Resolve Inflammation without Affecting the Fibrotic
      Response.
AB  - Lung fibrosis is characterized by abnormal accumulation of fibroblasts in the
      interstitium of the alveolar space. Two populations of myofibroblasts,
      distinguished by Thy1 expression, are detected in human and murine lungs.
      Accumulation of Thy1-negative (Thy1(-)) myofibroblasts was shown in the lungs of
      humans with idiopathic pulmonary fibrosis (IPF) and of bleomycin-treated mice. We
      aimed to identify genetic changes in lung myofibroblasts following Thy1
      crosslinking and assess the impact of specific lung myofibroblast Thy1
      deficiency, in vivo, in bleomycin-injured mouse lungs. Thy1 increased in mouse
      lung lymphocytes following bleomycin injury but decreased in myofibroblasts when
      fibrosis was at the highest point (14 days), as assessed by immunohistochemistry.
      Using gene chip analysis, we detected that myofibroblast Thy1 crosslinking
      mediates downregulation of genes promoting cell proliferation, survival, and
      differentiation, and reduces production of extracellular matrix (ECM) components,
      while concurrently mediating the upregulation of genes known to foster
      inflammation and immunological functions. Chimeric Thy1-deficient mice with
      Thy1(+) lymphocytes and Thy1(-) myofibroblasts showed fibrosis similar to wild
      type mice and an increased number of CD4/CD25 regulatory T cells, with a
      concomitant decrease in inflammation. Lung myofibroblasts downregulate Thy1
      expression to increase their proliferation but to diminish the in vivo
      inflammatory milieu. Inflammation is not essential for evolution of fibrosis as
      was previously stated. 

PMID- 26300594
TI  - How Concentration Shields Against Distraction.
AB  - In this article, we outline our view of how concentration shields against
      distraction. We argue that higher levels of concentration make people less
      susceptible to distraction for two reasons. One reason is that the undesired
      processing of the background environment is reduced. For example, when people
      play a difficult video game, as opposed to an easy game, they are less likely to
      notice what people in the background are saying. The other reason is that the
      locus of attention becomes more steadfast. For example, when people are watching
      an entertaining episode of their favorite television series, as opposed to a less
      absorbing show, attention is less likely to be diverted away from the screen by a
      ringing telephone. The theoretical underpinnings of this perspective, and
      potential implications for applied settings, are addressed.

PMID- 26300595
TI  - Bridging the gap between research into biological and psychosocial models of
      psychosis.
AB  - SUMMARY: Paul Bebbington's recent Special Article provides an excellent synthesis
      of recent advances in psychosocial research on psychosis. However, we doubt that
      a model based solely on social epidemiology and cognitive theory can totally
      describe psychosis, and to be fair, Bebbington does not suggest that it does. A
      complete model must also incorporate what we have learned from non-social
      epidemiology, neuroscience, and genetics. Evidence indicates that both the social
      risk factors that interest Bebbington and biological risk factors, such as abuse
      of stimulants and cannabis, can provoke psychotic symptoms by dysregulating
      striatal dopamine. The role of neurodevelopmental deviance also needs to be
      considered in the etiology of schizophrenia-like psychosis. Moreover, the
      striking advances in our understanding of the genetic architecture of psychosis
      open an exciting door into studies examining gene-environment correlation and
      gene-environment interaction. In short, Bebbington demonstrates the value of
      cognitive and social researchers talking to each other, but the occasional chat
      with the more biologically inclined could produce a more comprehensive model.

PMID- 26300596
TI  - Addressing risk of bias in trials of cognitive behavioral therapy.
AB  - A recent network meta-analysis by Zhu and colleagues reported in the Shanghai
      Archives of Psychiatry compared two different comparators (psychological placebo
      and waitlist control) in trials assessing the effectiveness of cognitive
      behavioral therapy (CBT) for the treatment of generalized anxiety disorder (GAD).
      CBT was superior to both of these control conditions, but psychological placebo
      was superior to waitlist. However, we argue that the term 'psychological placebo'
      is a misnomer because the impossibility of effectively blinding participants to
      treatment allocation in CBT trials makes it impossible to control for placebo
      effects. This failure to blind participants and therapists - and the resultant
      high risk of bias - was the main reason Zhu and colleagues found that the overall
      quality of the evidence supporting the conclusion that CBT is effective for GAD
      is poor. This is a general problem in all psychotherapy trials, which suffer from
      well-documented methodological and conceptual problems that prevent adequate
      placebo control and undermine casual inference. We discuss these problems and
      suggest potential solutions. We conclude that, while it may be difficult to
      remove potential bias in randomized controlled trials of psychotherapy, we can
      improve on the status quo by integrating basic science within applied trials to
      adjust for these biases and, thus, improve the strength of the causal inferences.

PMID- 26300597
TI  - Metacognitive training for schizophrenia: a systematic review.
AB  - BACKGROUND: Metacognitive training (MCT) is a novel group psychotherapy method
      for schizophrenia, but there is, as yet, no conclusive evidence of its efficacy.
      AIMS: Conduct a meta-analysis to assess the effectiveness of MCT in
      schizophrenia. METHODS: Electronic and hand searches were conducted to identify
      randomized controlled trials about the effects of MCT in schizophrenia that met
      pre-defined inclusion criteria. The Cochrane Risk of Bias tool was employed to
      assess of risk of biases, and Cochrane Review Manager version 5.3 and R version
      3.1.1 were used to conduct the data synthesis. RESULTS: Ten trials from 54
      unduplicated reports were included in the review, but differences in the methods
      of assessing outcomes limited the number of studies that could be included in the
      meta-analysis. Pooling four studies that assessed the positive symptom subscale
      of the Positive and Negative Syndrome Scale (PANSS) at the end of the trial
      identified a small but statistically significant greater reduction in the MCT
      group than in the control group. But pooling four studies that assessed the
      delusion subscale of the Psychotic Symptom Rating Scales (PSYRATS) at the end of
      the trial found no significant difference between the groups. Results from the
      qualitative assessment of the other results that could not be pooled across
      studies were mixed, some showed a trend in favor of MCT but many found no
      difference between the groups. CONCLUSIONS: The limited number of RCT trials, the
      variability of the method and time of the outcome evaluation, and methodological
      problems in the trials make it impossible to come to a conclusion about the
      effectiveness of MCT for schizophrenia. More randomized trials that use
      standardized outcome measures, that use intention-to-treat (ITT) analyses, and
      that follow-up participants at regular intervals after the intervention are
      needed to determine whether or not MCT should become a recommended adjunctive
      treatment for schizophrenia.

PMID- 26300598
TI  - Abnormal inter- and intra-hemispheric integration in male paranoid schizophrenia:
      a graph-theoretical analysis.
AB  - BACKGROUND: The human brain is a complex network of regions that are structurally
      interconnected by white matter (WM) tracts. Schizophrenia (SZ) can be
      conceptualized as a disconnection syndrome characterized by widespread
      disconnections in WM pathways. AIMS: To assess whether or not anatomical
      disconnections are associated with disruption of the topological properties of
      inter- and intra-hemispheric networks in SZ. METHODS: We acquired the diffusion
      tensor imaging data from 24 male patients with paranoid SZ during an acute phase
      of their illness and from 24 healthy age-matched male controls. The brain FA
      weighted (fractional anisotropy-weighted) structural networks were constructed
      and the inter- and intra-hemispheric integration was assessed by estimating the
      average characteristic path lengths (CPLs) between and within the left and right
      hemisphere networks. RESULTS: The mean CPLs for all 18 inter-and intra
      hemispheric CPLs assessed were longer in the SZ patient group than in the control
      group, but only some of these differences were significantly different: the CPLs
      for the overall inter-hemispheric and the left and right intra-hemispheric
      networks; the CPLs for the interhemisphere subnetworks of the frontal lobes,
      temporal lobes, and subcortical structures; and the CPL for the intra- frontal
      subnetwork in the right hemisphere. Among the 24 patients, the CPL of the inter
      frontal subnetwork was positively associated with negative symptom severity, but
      this was the only significant result among 72 assessed correlations, so it may be
      a statistical artifact. CONCLUSIONS: Our findings suggest that the integrity of
      intra- and inter-hemispheric WM tracts is disrupted in males with paranoid SZ,
      supporting the brain network disconnection model (i.e., the (')connectivity
      hypothesis(')) of schizophrenia. Larger studies with less narrowly defined
      samples of individuals with schizophrenia are needed to confirm these results.

PMID- 26300599
TI  - Controlled trial of the effectiveness of community rehabilitation for patients
      with schizophrenia in Shanghai, China.
AB  - BACKGROUND: The 'Sunshine Soul Park' is a network of social welfare institutions
      that provides communitybased rehabilitation services for individuals with mental
      illness. AIMS: Assess the effectiveness of the rehabilitation services provided
      at the 'Sunshine Soul Park' on the psychotic symptoms and social functioning of
      individuals with schizophrenia and, based on these findings, provide a
      theoretical model of community-based rehabilitation. METHODS: Sixty individuals
      with schizophrenia in the Huangpu District of Shanghai volunteered for the
      rehabilitation training program provided at six 'Sunshine Soul Park' community
      centers that involves day treatment, medication monitoring, biweekly
      rehabilitation training, and other recreational, social, and intellectual
      activities. A matched control group was recruited from individuals with
      schizophrenia registered on the Huangpu District registry of the 'Severe Mental
      Illness Prevention and Rehabilitation System'. All participants continued their
      medication without change for the full year of follow-up. Both groups were
      assessed at baseline, and 3, 6, and 12 months after enrollment using the Insight
      and Treatment Attitude Questionnaire (ITAQ), Social Disability Screening Schedule
      (SDSS), Generic Quality of Life Inventory-74 (GQOLI-74), and Positive and
      Negative Syndrome Scale (PANSS). RESULTS: In the intervention group the ITAQ,
      SDSS, GQOLI-74, and PANSS scores showed statistically significant improvement
      compared to baseline at each follow-up assessment. Moreover, the trend in
      improvement in the interventions group is significantly faster than that in the
      control group. CONCLUSIONS: The 'Sunshine Soul Park' rehabilitation training
      program enhances patients' knowledge about their disorder and improves their
      social functioning and quality of life. Further studies to assess methods for up
      scaling this intervention to other areas of China are warranted.

PMID- 26300600
TI  - Comparisons of family environment between homeless and non-homeless individuals
      with schizophrenia in Xiangtan, Hunan.
AB  - BACKGROUND: Homelessness is an increasingly important problem for individuals
      with serious mental illness in China. AIM: Identify the characteristics of
      families that are associated with homelessness among individuals with
      schizophrenia. METHODS: Participants were 1856 homeless individuals with
      schizophrenia (defined as those who had no place of residence or involved
      caregivers for 7 consecutive days) and 1728 non-homeless individuals with
      schizophrenia from Xiangtan, Hunan. The self-completion Family Environment Scale
      Chinese Version (FES-CV) was administered to these participants after their acute
      psychotic symptoms resolved. RESULTS: Compared to individuals in the non-homeless
      group, those in the homeless group were older and more likely to be non-locals
      (i.e., from outside of Xiangtan), be residents of rural (versus urban)
      communities, have temporary (versus permanent) jobs, be married, and have a low
      level of education. After controlling for demographic differences using
      multivariate logistic regression models, homelessness was independently
      associated higher scores in the FES-CV intellectual-cultural orientation,
      organization, achievement orientation, and control subscales and with lower
      scores in the FES-CV cohesion, moralreligious emphasis, independence, and active
      recreational orientation subscales. CONCLUSION: After controlling for
      sociodemographic factors, certain aspects of the family environment areassociated
      with being homeless among patients with schizophrenia in China. Further work is
      needed to identify interventions that can reduce the risk of homelessness in high
      risk individuals.

PMID- 26300601
TI  - Oligodendroglioma presenting as chronic mania.
AB  - SUMMARY: Oligodendrogliomas may present with a variety of psychological symptoms
      but it only rarely presents with mania. The patient described in this case report
      is a 55-year-old man with a three year history of progressive mania who was
      initially diagnosed as chronic mania but a subsequent MRI identified a brain
      tumor. This report highlights the importance of considering differential organic
      diagnosis when patients present with atypical presentations of psychiatric
      disorders. A brain tumor should be considered and brain imaging studies conducted
      for patients with a late age of onset who do not respond to appropriate
      medication.

PMID- 26300602
TI  - Development of a checklist of short-term and long-term psychological symptoms
      associated with ketamine use.
AB  - BACKGROUND: Ketamine is an increasingly popular drug of abuse in China but there
      is currently no method for classifying the psychological effects of ketamine in
      individuals with ketamine dependence. AIM: Develop a scale that characterizes the
      acute and long-term psychological effects of ketamine use among persons with
      ketamine dependence. METHODS: We developed a preliminary symptom checklist with
      35 dichotomous ('yes' or 'no') items about subjective feelings immediately after
      ketamine use and about perceived long-term effects of ketamine use that was
      administered to 187 inpatients with ketamine dependence recruited from two large
      hospitals in Guangzhou, China. Exploratory factor analysis (EFA) was conducted on
      a randomly selected half of thesample to reduce the items and to identify
      underlying constructs. Confirmatory factor analysis (CFA) was conducted on the
      second half of the sample to assess the robustness of the identified factor
      structure. RESULTS: Among the 35 symptoms, the most-reported acute effects were
      'floating or circling' (94%), 'euphoric when listening to rousing music' (86%),
      and 'feeling excited, talkative, and full of energy' (67%). The mostreported long
      term symptoms were 'memory impairment' (93%), 'personality changes' (86%), and
      'slowed reactions' (81%). EFA resulted in a final 22-item scale best modelled by
      a four-factor model: two factors representing chronic symptoms (social withdrawal
      and sleep disturbances), one about acute psychoticlike symptoms, and one that
      combined acute drug-related euphoria and longer-term decreased libido. CFA showed
      that these 4 factors accounted for 50% of the total variance of the final 22-item
      scale and that the model fit was fair (Goodness of Fit Index, GIF=83.3%; Root
      Mean Square Error of Approximation, RMSEA=0.072). CONCLUSION: A four-factor model
      including social withdrawal, sleep disturbance, psychotic-like symptoms, and
      euphoria at the time of drug use provides a fair description of the short-term
      and long-term psychological symptoms associated with ketamine use. Future work on
      the 22-item version of the scale with larger samples is needed to confirm the
      validity of this 4-factor structure, to assess the scale's test-retest
      reliability, and to determine whether or not it can be useful in the differential
      diagnosis and monitoring of treatment of individuals with ketamine dependence.

PMID- 26300603
TI  - Meta-analysis for psychiatric research using free software R.
AB  - SUMMARY: This paper provides a brief overview of meta-analysis (MA) with emphasis
      on classical fixedeffects and random-effects MA models. It illustrates the
      application of MA models with the open-source software R using publicly available
      data from five studies on lamotrigine to treat bipolar depression and finds that
      meta-analysis identifies a statistically significant advantage of lamotrigine
      over placebo that was not evident in the individual studies.

PMID- 26300604
TI  - Interventions to Increase Access to Care and Quality of Care for Women With
      Gestational Diabetes.

PMID- 26300605
TI  - Diabetic Kidney Disease: Much Progress, But Still More to Do.

PMID- 26300607
TI  - Guest Editor.

PMID- 26300606
TI  - Diabetic Kidney Disease: A Call to Action: Preface.

PMID- 26300608
TI  - Laboratory Assessment of Diabetic Kidney Disease.
AB  - IN BRIEF Regardless of etiology, chronic kidney disease (CKD) is identified by
      two laboratory tests: 1) estimated glomerular filtration rate (eGFR), a measure
      of kidney function, and 2) urine albumin-to-creatinine ratio (UACR), a measure of
      kidney damage. It is crucial for all health professionals to understand the
      significance and limitations of these tests to appropriately identify CKD
      patients, guide therapy, and determine prognosis. This article provides
      information that will enable diabetes educators and other clinicians to properly
      interpret eGFR and UACR laboratory results in the identification and management
      of CKD. 

PMID- 26300609
TI  - Novel Therapies for Diabetic Kidney Disease: Storied Past and Forward Paths.
AB  - IN BRIEF Current therapeutic approaches are only moderately efficacious at
      preventing the progression of diabetic kidney disease (DKD). As the number of
      people with DKD continues to rise worldwide, there is an urgent need for novel
      therapies. A better understanding of the root causes and molecular mechanisms of
      DKD pathogenesis has enabled the identification of numerous new therapeutic
      targets, including advanced glycation end products, reactive oxygen species,
      protein kinase C, and serum amyloid A. Although experimental studies have
      illustrated the potential of such approaches, challenges in clinical translation
      remain a barrier in therapeutic development. Advances in preclinical safety and
      efficacy evaluations and improved delivery systems may aid in clinical
      translation of novel DKD therapies. 

PMID- 26300610
TI  - Hypertension Management in Diabetic Kidney Disease.
AB  - IN BRIEF Hypertension is prevalent in most individuals with diabetic kidney
      disease (DKD). Failure to treat hypertension appropriately in this subgroup of
      patients results in an increased risk of cardiovascular morbidity and mortality,
      as well as a faster progression of kidney disease. The current guidance for
      appropriate treatment of hypertension in this high-risk population provides an
      opportunity to improve both kidney and cardiovascular outcomes. This review
      discusses the current state of evidence-based hypertension management in patients
      with DKD. 

PMID- 26300611
TI  - Nutrition Intervention for Advanced Stages of Diabetic Kidney Disease.
AB  - IN BRIEF For the goals of reducing diabetic kidney disease (DKD) onset and
      progression, approaches to nutritional therapy are a subject of much debate. This
      article discusses selected nutrients that have a role in affecting DKD outcomes
      and introduces application of newer, individualized concepts for healthful
      eating, as supported by clinical evidence relevant to patients with DKD. Selected
      aspects of management of advanced DKD are also reviewed. 

PMID- 26300612
TI  - Comprehensive Care for People With Diabetic Kidney Disease.
AB  - IN BRIEF Diabetic kidney disease carries a heavy burden, both economically and in
      terms of quality of life, largely because of its very high risk for vascular
      disease. Coordinated, multidisciplinary care with attention to appropriate,
      timely screening and preventive management is crucial to reducing the morbidity
      and mortality of this devastating disease. 

PMID- 26300613
TI  - Care Utilization Patterns and Diabetes Self-Management Education Duration.
AB  - Objective. Previous studies have shown that receiving diabetes self-management
      education (DSME) is associated with increased care utilization. However, the
      relationship between DSME duration and care utilization patterns remains largely
      unexamined. Our purpose is to characterize DSME duration and examine the
      relationship between DSME duration and clinical- and self-care utilization
      patterns. Methods. The study sample included 1,446 adults who were >=18 years of
      age, had diabetes, and had participated in the 2008 Florida Behavioral Risk
      Factor Surveillance System survey. Clinical- and self-care outcomes were derived
      using responses to the survey's diabetes module and were based on minimum
      standards of care established by the American Diabetes Association. The outcomes
      examined included self-monitoring of blood glucose at least once per day;
      receiving at least one eye exam, one foot exam, A1C tests, and an influenza
      vaccination in the past year; and ever receiving a pneumococcal vaccination. DSME
      duration was categorized as no DSME, >0 to <4 hours, 4-10 hours, and >10 hours.
      Results. After adjusting for sociodemographic variables, compared to those who
      did not receive DSME, those who had 4-10 or 10+ hours of DSME were more likely to
      receive two A1C tests (odds ratio [95% CI] 2.69 [1.30-5.58] and 2.63 [1.10-6.31],
      respectively) and have a pneumococcal vaccination (1.98 [1.03-3.80] and 1.92
      [1.01-3.64], respectively). Those receiving 10+ hours of DSME were 2.2 times (95%
      CI 1.18-4.09) as likely to have an influenza vaccination. Conclusion. These data
      reveal a positive relationship between DSME duration and utilization of some
      diabetes clinical care services. 

PMID- 26300614
TI  - Selecting an A1C Point-of-Care Instrument.
AB  - A1C point-of-care (POC) instruments benefit patients with diabetes by
      facilitating clinician decision making that results in significant glycemic
      improvements. Three National Glycohemoglobin Standardization Program (NGSP)
      certified POC products are available in the United States: the handheld A1CNow
      (formerly manufactured by Bayer Diabetes Care but now made by Chek Diagnostics)
      and two bench-top models called the Axis-Shield Afinion Analyzer and the Siemens
      DCA Vantage. This article compares the three available NGSP-certified POC
      products in terms of accuracy, precision, ease of use, cost, and additional
      features. Its goal is to aid health care facilities in conveniently identifying
      the A1C POC product that best meets their needs. It additionally reviews evidence
      that supports the continued use of A1C POC instruments in the clinical arena. 

PMID- 26300615
TI  - Clinical Insights Into a New, Disposable Insulin Delivery Device.

PMID- 26300616
TI  - Management of Hyperglycemia in Diabetic Kidney Disease.

PMID- 26300617
TI  - Hypertension and Diabetic Kidney Disease in Children and Adolescents.

PMID- 26300618
TI  - Enhanced light trapping in solar cells using snow globe coating.
AB  - A novel method, snow globe coating, is found to show significant enhancement of
      the short circuit current JSC (35%) when applied as a scattering back reflector
      for polycrystalline silicon thin-film solar cells. The coating is formed from
      high refractive index titania particles without containing binder and gives close
      to 100% reflectance for wavelengths above 400 nm. Snow globe coating is a
      physicochemical coating method executable in pH neutral media. The mild
      conditions of this process make this method applicable to many different types of
      solar cells.

PMID- 26300619
TI  - Employing Si solar cell technology to increase efficiency of ultra-thin
      Cu(In,Ga)Se2 solar cells.
AB  - Reducing absorber layer thickness below 500 nm in regular Cu(In,Ga)Se2 (CIGS)
      solar cells decreases cell efficiency considerably, as both short-circuit current
      and open-circuit voltage are reduced because of incomplete absorption and high
      Mo/CIGS rear interface recombination. In this work, an innovative rear cell
      design is developed to avoid both effects: a highly reflective rear surface
      passivation layer with nano-sized local point contact openings is employed to
      enhance rear internal reflection and decrease the rear surface recombination
      velocity significantly, as compared with a standard Mo/CIGS rear interface. The
      formation of nano-sphere shaped precipitates in chemical bath deposition of CdS
      is used to generate nano-sized point contact openings. Evaporation of MgF2 coated
      with a thin atomic layer deposited Al2O3 layer, or direct current magnetron
      sputtering of Al2O3 are used as rear surface passivation layers. Rear internal
      reflection is enhanced substantially by the increased thickness of the
      passivation layer, and also the rear surface recombination velocity is reduced at
      the Al2O3/CIGS rear interface. (MgF2/)Al2O3 rear surface passivated ultra-thin
      CIGS solar cells are fabricated, showing an increase in short circuit current and
      open circuit voltage compared to unpassivated reference cells with equivalent
      CIGS thickness. Accordingly, average solar cell efficiencies of 13.5% are
      realized for 385 nm thick CIGS absorber layers, compared with 9.1% efficiency for
      the corresponding unpassivated reference cells.

PMID- 26300620
TI  - Maternal Obesity and Rectovaginal Group B Streptococcus Colonization at Term.
AB  - OBJECTIVE: To test the hypothesis that maternal obesity is an independent risk
      factor for rectovaginal group B streptococcus (GBS) colonization at term. STUDY
      DESIGN: Retrospective cohort study of consecutive women with singleton term
      pregnancies admitted in labor at Barnes-Jewish Hospital (2004-2008). Maternal
      BMI>=30 Kg/m2 (obese) or <30 Kg/m2 (nonobese) defined the two comparison groups.
      The outcome of interest was GBS colonization from a positive culture. Baseline
      characteristics were compared using Student's t-test and Chi-squared or Fisher's
      exact test. The association between obesity and GBS colonization was assessed
      using univariable and multivariable analyses. RESULTS: Of the 10,564 women
      eligible, 7,711 met inclusion criteria. The prevalence of GBS colonization in the
      entire cohort was relatively high (25.8%). Obese gravidas were significantly more
      likely to be colonized by GBS when compared with nonobese gravidas (28.4% versus
      22.2%, P<0.001). Obese gravidas were still 35% more likely than nonobese women to
      test positive for GBS after adjusting for race, parity, smoking, and diabetes
      (adjusted OR 1.35 [95% CI 1.21-1.50]). CONCLUSION: Maternal obesity is a
      significant risk factor for GBS colonization at term. Further research is needed
      to evaluate the impact of this finding on risk-based management strategies.

PMID- 26300621
TI  - Middle School Drinking: Who, Where, and When.
AB  - The goal of this research was to describe the most common drinking situations for
      young adolescents (N=1171; 46.6% girls), as well as determine predictors of their
      drinking in the seventh and eighth grades. Middle school students most frequently
      drank at parties with three to four teens, in their home or at a friend's home,
      and reported alcohol-related problems including conflicts with friends or
      parents, memory loss, nausea, and doing things they would not normally do.
      Differences emerged in predicting higher levels of drinking on the basis of sex,
      race, grade, positive alcohol expectancies, impulsivity, and peer drinking. These
      findings suggest both specific and general factors are implicated in drinking for
      middle school students. Contextual factors, including drinking alone, in public
      places, and at or near school, are characteristic of the most problematic alcohol
      involvement in middle school and may have utility in prevention and early
      intervention.

PMID- 26300622
TI  - Identity Development in a Transracial Environment: Racial/Ethnic Minority
      Adoptees in Minnesota.
AB  - It has been argued that transracial adopted children have increased risk for
      problems related to self-esteem and ethnic identity development. We evaluated
      this hypothesis across four groups of transracial adoptees: Asian (N = 427),
      Latino (N = 28), Black (N = 6), Mixed/Other (N = 20), and same-race white
      adoptees (N = 126) from 357 adoptive families. No mean differences were found in
      adoptee's ratings of affect about adoption, or of curiosity about birthparents.
      Some differences were found in general identity development and adjustment. There
      were notable differences in communication about race/ethnicity across groups and
      between parent and child report.

PMID- 26300623
TI  - Preretinal hemorrhage as a presenting sign of idiopathic macular telangiectasia
      type 2.
AB  - We report three cases of idiopathic macular telangiectasia type 2 with temporally
      decentered preretinal hemorrhage as the presenting sign. The preretinal blood
      obscured the telangiectatic vessels such that the diagnosis was only evident by
      fluorescein angiography of the fellow eyes, which had near-normal vision. The
      preretinal hemorrhage was associated with Valsalva maneuver in one patient and
      with type 3 subretinal neovascularization in one patient. We speculate that the
      vascular dilations in idiopathic macular telangiectasia type 2 may increase
      patients' susceptibility to rupture and hemorrhage with increased venous
      pressure. 

PMID- 26300624
TI  - Comparison between bimatoprost and latanoprost-timolol fixed combination for
      efficacy and safety after switching patients from latanoprost.
AB  - BACKGROUND: The purpose of this study was to prospectively evaluate and compare
      intraocular pressure (IOP) reduction efficacy and safety between bimatoprost and
      latanoprost-timolol fixed combination (LTFC) in Japanese patients with open-angle
      glaucoma. METHODS: In this prospective, randomized, non-masked study, after
      enrolling 70 eyes of 70 Japanese open-angle glaucoma patients who had used
      latanoprost monotherapy for more than 4 weeks, the subjects were randomly divided
      into a bimatoprost group or an LTFC group. Both groups were switched from
      latanoprost to bimatoprost or LTFC for 12 weeks. IOP, conjunctival injection
      score, corneal epitheliopathy score (area density classification; AD score), tear
      film break-up time, heart rate, and blood pressure were evaluated at 0, 4, and 12
      weeks after switching. The paired t-test and Mann-Whitney U-test were used for
      the statistical analysis. RESULTS: After 13 of the 70 patients dropped out, 57
      were analyzed for IOP reduction and safety. There was a significant decrease in
      mean IOP at 4 weeks compared with week 0 in both groups (both P<0.0001).
      Comparisons between the two groups showed no statistically significant
      differences. The conjunctival injection score was higher in the bimatoprost group
      than in the LTFC group at 12 weeks (P=0.0091). There were no statistically
      significant differences between the two drugs in relation to AD score, tear film
      break-up time, heart rate, and blood pressure. CONCLUSION: Bimatoprost and LTFC
      exhibited similar efficacy for reduction of IOP. Safety results indicated that
      only the conjunctival injection score at 12 weeks was higher in the bimatoprost
      group compared with the LTFC group.

PMID- 26300625
TI  - Folate status in type 2 diabetic patients with and without retinopathy.
AB  - BACKGROUND: Folate deficiency is associated with cardiovascular disease,
      megaloblastic anemia, and with hyperhomocysteinemia. This study has been
      undertaken to investigate the role of folate status during the progression of the
      diabetic retinopathy. METHODS: We measured the plasma levels of homocysteine,
      folic acid, and red cell folate in 70 diabetic type 2 patients with
      nonproliferative diabetic retinopathy (NPDR), 65 with proliferative diabetic
      retinopathy (PDR), 96 without diabetic retinopathy, and 80 healthy subjects used
      as a control group. RESULTS: We found higher plasma levels of homocysteine in the
      NPDR group compared to the control group (P<0.001) and in the PDR group compared
      to control group (P<0.001) and NPDR group (P<0.01). The severity of diabetic
      retinopathy was associated with lower folic acid and red cell folate levels, and
      a significant difference was observed between PDR and NPDR groups (P<0.05).
      CONCLUSION: The folate status could play a role in the development and
      progression of diabetic retinopathy.

PMID- 26300626
TI  - Evaluation of glycine-bearing celecoxib derivatives as a colon-specific mutual
      prodrug acting on nuclear factor-kappaB, an anti-inflammatory target.
AB  - In an inflammatory state where HOCl is generated, glycine readily reacts with
      HOCl to produce glycine chloramine, an anti-inflammatory oxidant. Colonic
      delivery of celecoxib elicits anticolitic effects in a trinitrobenzene sulfonic
      acid-induced rat colitis model. Glycine-bearing celecoxib derivatives were
      prepared and evaluated as a colon-specific mutual prodrug acting on nuclear
      factor-kappaB (NFkappaB), an anticolitic target. Glycylcelecoxib (GC), N
      glycylaspart-1-ylcelecoxib (N-GA1C), and C-glycylaspart-1-ylcelecoxib (C-GA1C)
      were synthesized and their structures identified using infrared and proton
      nuclear magnetic resonance spectrometer. The celecoxib derivatives were
      chemically stable in pH 6.8 and 1.2 buffers. GC and C-GA1C were resistant to
      degradation in the small intestinal contents, while N-GA1C was substantially
      cleaved to release celecoxib. In contrast, all the celecoxib derivatives were
      degraded to liberate celecoxib in the cecal content. These results suggest that
      GC and C-GA1C could be delivered to and liberate celecoxib and glycine in the
      large intestine. In human colon carcinoma HCT116 and murine macrophage RAW264.7
      cells, combined celecoxib-glycine chloramine treatment additively suppressed the
      production of proinflammatory NFkappaB target gene products. Collectively, our
      data suggest that C-GA1C is a potential colon-specific mutual prodrug acting
      against NFkappaB. 

PMID- 26300627
TI  - Glycemic control and antidiabetic drugs in type 2 diabetes mellitus patients with
      renal complications.
AB  - BACKGROUND: Good glycemic control can delay the progression of kidney diseases in
      type 2 diabetes mellitus (T2DM) patients with renal complications. To date, the
      association between antidiabetic agents and glycemic control in this specific
      patient population is not well established. PURPOSE: This study aimed to identify
      antidiabetic regimens as well as other factors that associated with glycemic
      control in T2DM patients with different stages of chronic kidney disease (CKD).
      PATIENTS AND METHODS: This retrospective, cross-sectional study involved 242 T2DM
      inpatients and outpatients with renal complications from January 2009 to March
      2014 and was conducted in a tertiary teaching hospital in Malaysia. Glycated
      hemoglobin (A1C) was used as main parameter to assess patients' glycemic status.
      Patients were classified to have good (A1C <7%) or poor glycemic control (A1C
      >=7%) based on the recommendations of the American Diabetes Association. RESULTS:
      Majority of the patients presented with CKD stage 4 (43.4%). Approximately 55.4%
      of patients were categorized to have poor glycemic control. Insulin (57.9%) was
      the most commonly prescribed antidiabetic medication, followed by sulfonylureas
      (43%). Of all antidiabetic regimens, sulfonylureas monotherapy (P<0.001), insulin
      therapy (P=0.005), and combination of biguanides with insulin (P=0.038) were
      found to be significantly associated with glycemic control. Other factors
      including duration of T2DM (P=0.004), comorbidities such as anemia (P=0.024) and
      retinopathy (P=0.033), concurrent medications such as erythropoietin therapy
      (P=0.047), alpha-blockers (P=0.033), and antigouts (P=0.003) were also correlated
      with A1C. CONCLUSION: Identification of factors that are associated with glycemic
      control is important to help in optimization of glucose control in T2DM patients
      with renal complication.

PMID- 26300628
TI  - High-throughput sequencing of 16S rDNA amplicons characterizes bacterial
      composition in cerebrospinal fluid samples from patients with purulent
      meningitis.
AB  - Purulent meningitis (PM) is a severe infectious disease that is associated with
      high rates of morbidity and mortality. It has been recognized that bacterial
      infection is a major contributing factor to the pathogenesis of PM. However,
      there is a lack of information on the bacterial composition in PM, due to the low
      positive rate of cerebrospinal fluid bacterial culture. Herein, we aimed to
      discriminate and identify the main pathogens and bacterial composition in
      cerebrospinal fluid sample from PM patients using high-throughput sequencing
      approach. The cerebrospinal fluid samples were collected from 26 PM patients, and
      were determined as culture-negative samples. The polymerase chain reaction
      products of the hypervariable regions of 16S rDNA gene in these 26 samples of PM
      were sequenced using the 454 GS FLX system. The results showed that there were
      71,440 pyrosequencing reads, of which, the predominant phyla were Proteobacteria
      and Firmicutes; and the predominant genera were Streptococcus, Acinetobacter,
      Pseudomonas, and Neisseria. The bacterial species in the cerebrospinal fluid were
      complex, with 61.5% of the samples presenting with mixed pathogens. A significant
      number of bacteria belonging to a known pathogenic potential was observed. The
      number of operational taxonomic units for individual samples ranged from six to
      75 and there was a comparable difference in the species diversity that was
      calculated through alpha and beta diversity analysis. Collectively, the data show
      that high-throughput sequencing approach facilitates the characterization of the
      pathogens in cerebrospinal fluid and determine the abundance and the composition
      of bacteria in the cerebrospinal fluid samples of the PM patients, which may
      provide a better understanding of pathogens in PM and assist clinicians to make
      rational and effective therapeutic decisions. 

PMID- 26300630
TI  - The efficacy and safety of panitumumab in the treatment of patients with
      metastatic colorectal cancer: a meta-analysis from five randomized controlled
      trials.
AB  - BACKGROUND: The efficacy of adding panitumumab to chemotherapy remains
      controversial in the treatment of metastatic colorectal cancer (mCRC). Thus, we
      conducted this meta-analysis to assess the efficacy and safety of this
      combination regimen in patients with mCRC. METHODS: The PubMed, Embase, and Web
      of Science databases were comprehensively searched. Eligible studies included
      randomized controlled trials (RCTs) that estimated the efficacy of panitumumab
      with or without chemotherapy in the treatment of patients with mCRC. Hazard ratio
      (HR), risk ratio (RR), and 95% confidence intervals (CIs) were calculated, and
      heterogeneity was tested using I (2) statistics. RESULTS: Four studies involving
      a total of 3,066 patients were included in this meta-analysis. The addition of
      panitumumab to chemotherapy significantly improved progression-free survival
      (PFS) (HR =0.84, 95% CI =0.78-0.91, P=0.000) and the objective response rate
      (ORR) (RR =2.18, 95% CI =1.13-4.22, P=0.021) compared to chemotherapy alone, but
      no effect was noted on overall survival (OS) (HR =0.97, 95% CI =0.89-1.05,
      P=0.402). Subgroup analysis based on KRAS gene status revealed that the combined
      therapy significantly improved PFS (HR =0.71, 95% CI =0.57-0.88, P=0.002) and ORR
      (RR =2.43, 95% CI =1.21-4.90, P=0.013) in patients with wild-type KRAS tumors.
      Irinotecan-based chemotherapy plus panitumumab significantly prolonged PFS in
      patients with mCRC (HR =0.84, 95% CI =0.76-0.94, P=0.002). The combined treatment
      also increased the incidence of grade 3/4 adverse events. CONCLUSION: This meta
      analysis indicates that the combination of panitumumab and chemotherapy
      effectively improved PFS and ORR, but it did not prolong OS. However, as the
      number of studies in the meta-analysis was limited, more large-scale, better
      designed RCTs are needed to assess the combination of panitumumab and
      chemotherapy.

PMID- 26300629
TI  - Novel targeting of PEGylated liposomes for codelivery of TGF-beta1 siRNA and four
      antitubercular drugs to human macrophages for the treatment of mycobacterial
      infection: a quantitative proteomic study.
AB  - Tuberculosis (TB) is still a major public health issue in developing countries,
      and its chemotherapy is compromised by poor drug compliance and severe side
      effects. This study aimed to synthesize and characterize new multimodal PEGylated
      liposomes encapsulated with clinically commonly used anti-TB drugs with linkage
      to small interfering RNA (siRNA) against transforming growth factor-beta1 (TGF
      beta1). The novel NP-siRNA liposomes could target THP-1-derived human macrophages
      that were the host cells of mycobacterium infection. The biological effects of
      the NP-siRNA liposomes were evaluated on cell cycle distribution, apoptosis,
      autophagy, and the gene silencing efficiency of TGF-beta1 siRNA in human
      macrophages. We also explored the proteomic responses to the newly synthesized NP
      siRNA liposomes using the stable isotope labeling with amino acids in cell
      culture approach. The results showed that the multifunctional PEGylated liposomes
      were successfully synthesized and chemically characterized with a mean size of
      265.1 nm. The novel NP-siRNA liposomes functionalized with the anti-TB drugs and
      TGF-beta1 siRNA were endocytosed efficiently by human macrophages as visualized
      by transmission electron microscopy and scanning electron microscopy.
      Furthermore, the liposomes showed a low cytotoxicity toward human macrophages.
      There was no significant effect on cell cycle distribution and apoptosis in THP-1
      derived macrophages after drug exposure at concentrations ranging from 2.5 to
      62.5 MUg/mL. Notably, there was a 6.4-fold increase in the autophagy of human
      macrophages when treated with the NP-siRNA liposomes at 62.5 MUg/mL. In addition,
      the TGF-beta1 and nuclear factor-kappaB expression levels were downregulated by
      the NP-siRNA liposomes in THP-1-derived macrophages. The Ingenuity Pathway
      Analysis data showed that there were over 40 signaling pathways involved in the
      proteomic responses to NP-siRNA liposome exposure in human macrophages, with 160
      proteins mapped. The top five canonical signaling pathways were eukaryotic
      initiation factor 2 signaling, actin cytoskeleton signaling, remodeling of
      epithelial adherens junctions, epithelial adherens junction signaling, and Rho
      GDP-dissociation inhibitor signaling pathways. Collectively, the novel synthetic
      targeting liposomes represent a promising delivery system for anti-TB drugs to
      human macrophages with good selectivity and minimal cytotoxicity. 

PMID- 26300631
TI  - Retrospective comparison of the effects of epidural anesthesia versus peripheral
      nerve block on postoperative outcomes in elderly Chinese patients with femoral
      neck fractures.
AB  - BACKGROUND: Geriatric patients with femoral neck fracture (FNF) have unacceptably
      high rates of postoperative complications and mortality. The purpose of this
      study was to compare the effects of epidural anesthesia versus peripheral nerve
      block (PNB) on postoperative outcomes in elderly Chinese patients with FNF.
      METHODS: This retrospective study explored mortality and postoperative
      complications in geriatric patients with FNF who underwent epidural anesthesia or
      PNB at the Chinese People's Liberation Army General Hospital from January 2008 to
      December 2012. The electronic database at the Chinese People's Liberation Army
      General Hospital includes discharge records for all patients treated in the
      hospital. Information on patient demographics, preoperative comorbidity,
      postoperative complications, type of anesthesia used, and in-hospital, 30-day,
      and 1-year mortality after surgery was obtained from this database. RESULTS: Two
      hundred and fifty-eight patients were identified for analysis. The mean patient
      age was 79.7 years, and 71.7% of the patients were women. In-hospital, 30-day,
      and 1-year postoperative mortality was 4.3%, 12.4%, and 22.9%, respectively, and
      no differences in mortality or cardiovascular complications were found between
      patients who received epidural anesthesia and those who received PNB. More
      patients with dementia or delirium were given PNB. No statistically significant
      differences were found between groups for other comorbidities or intraoperative
      parameters. The most common complications were acute cardiovascular events
      (23.6%), electrolyte disturbances (20.9%), and hypoxemia (18.2%). Patients who
      received PNB had more postoperative delirium (P=0.027). Postoperative acute
      respiratory events were more common (P=0.048) and postoperative stroke was less
      common (P=0.018) in the PNB group. There were fewer admissions to intensive care
      (P=0.024) in the epidural anesthesia group. Key factors with a negative influence
      on mortality were acute cardiovascular events, dementia, male sex, age, American
      Society of Anesthesiologists score, acute respiratory events, intensive care
      admission, and comorbidities. CONCLUSION: PNB was not associated with lower
      mortality or lower cardiovascular complication rates when compared with epidural
      anesthesia in elderly patients with FNF.

PMID- 26300632
TI  - Is oxycodone/naloxone effective and safe in managing chronic pain of a fragile
      elderly patient with multiple skin ulcers of the lower limbs? A case report.
AB  - Skin ulcers are a common issue in the elderly, as physiological loss of skin
      elasticity, alterations in microcirculation, and concomitant chronic diseases
      typically occur in advanced age, thereby predisposing to these painful lesions.
      Wound-related pain is often associated with skin ulcers and negatively impacts
      both the patient's quality of life and, indirectly, wound healing. Pain
      management is an ongoing issue in the elderly, and remains underestimated and
      under-treated in this fragile population. Recent guidelines suggest the use of
      opioids as the frontline treatment of moderate and severe pain in nononcological
      pain in the elderly. However, due to the concerns of adverse reactions, drug
      interactions, and addiction, clinicians frequently hesitate to prescribe opioids.
      This case report describes an elderly diabetic patient with multiple ulcers of
      the lower limbs suffering wound-related pain. In our report, oxycodone/naloxone
      has proved to be an effective and safe drug, providing pain relief as well as
      increased compliance when redressing wounds and faster healing compared to that
      in similar patients. Our case provides anecdotal evidence, supported by other
      studies, to justify future, larger studies on chronic pain using this therapy. 

PMID- 26300633
TI  - Assessment of the risk of falling with the use of timed up and go test in the
      elderly with lower extremity osteoarthritis.
AB  - BACKGROUND: Falling in the elderly results in a significant number of admissions
      to hospitals and long-term care facilities, especially among patients with lower
      extremity osteoarthritis (OA). OBJECTIVE: The aim of the study was to assess the
      risk of falling in adults older than 60 years with OA using timed up and go (TUG)
      test. MATERIALS AND METHODS: A total of 187 patients (aged >60 years) were
      enrolled in the study. The assessment included: basic activities of daily living
      (ADLs), lower extremity strength with the use of the 30-second chair stand test
      (30 CST), and assessment of the risk of falling (TUG test). Pain intensity was
      evaluated with the numeric rating scale (NRS). RESULTS: The TUG test results were
      significantly better in younger OA patients (aged 60-69 years), as compared with
      their older peers (aged 70-79 years; P<0.01) and the oldest group (aged >80
      years; P<0.001). Also, the 30 CST results were significantly higher in younger OA
      patients (P<0.05). Subjects older than 80 years had a significantly worse ADL
      score (P<0.05 and P<0.001). Pain complaints were reported significantly more
      frequently by women than men (P<0.05). A correlation between age and the TUG test
      score (r=0.412; P<0.0004) as well as between the TUG test and the 30 CST scores
      (r=0.7368; P=0.000) was detected. In the group with the TUG test score of <13.5
      seconds, the 30 CST (P<0.0001) and ADL (P<0.003) results were significantly
      better. A comparison of fallers vs nonfallers revealed that the number of falls
      was significantly higher in the group of subjects who scored >=13.5 when compared
      to <13.5 (P=0.003). Fallers significantly more often reported pain (P<0.0001),
      whereas nonfallers had significantly better 30 CST results (P=0.0003).
      CONCLUSION: Elderly population with OA is at an elevated risk of falling, which
      increases with progressing age, pain, and muscle weakness. It seems prudent to
      identify individuals at a high risk of falling and to propose an adequate
      treatment for them.

PMID- 26300634
TI  - Resistance training improves isokinetic strength and metabolic syndrome-related
      phenotypes in postmenopausal women.
AB  - PURPOSE: To examine the effects of resistance training (RT) on metabolic syndrome
      related phenotypes in postmenopausal women. PATIENTS AND METHODS: Twenty-two
      postmenopausal women (65.0+/-4.2 years) underwent 12 weeks of whole body
      progressive training with intensity prescribed based on rating of perceived
      exertion. Dominant knee extension strength was assessed using an isokinetic
      dynamometer before and after the intervention. Moreover, all volunteers had blood
      samples collected for lipid profile, glycemic control, and C-reactive protein
      analyses. Waist circumference and arterial blood pressure were also measured at
      baseline and after the training period. Student's t-tests for paired samples and
      repeated measures ANOVA were used to compare dependent variables, and statistical
      significance was set at P<0.05. RESULTS: Isokinetic muscle strength significantly
      increased (P<0.01) with training. It was observed that waist circumference as
      well as total and low-density lipoprotein cholesterol levels significantly
      decreased with training (P<0.01). Total cholesterol/high-density lipoprotein
      cholesterol ratio, an important marker of cardiovascular disease incidence, was
      also significantly reduced (from 3.91+/-0.91 to 3.60+/-0.74; P<0.01) after the
      program. Blood glucose, basal insulin, and homeostatic model assessment of
      insulin resistance were also significantly reduced (P<0.01). No significant
      alterations were observed for resting blood pressure, triglycerides, or C
      reactive protein. CONCLUSION: Based on the observed results, it can be concluded
      that a 12-week progressive RT program, besides increasing isokinetic muscle
      strength, induces beneficial alterations on metabolic syndrome-related phenotypes
      in postmenopausal women. These findings highlight this mode of exercise as an
      important component of public health promotion programs for aged women. RT
      improves isokinetic strength and metabolic syndrome-related phenotypes in
      postmenopausal women.

PMID- 26300635
TI  - Sex differences in use of inhalants by elderly patients with asthma.
AB  - BACKGROUND: The number of elderly patients with asthma has been increasing in
      Japan. Treatment for these patients should be provided based on the condition of
      individual patients. This study was performed to clarify the relationship between
      inhalation procedure and sex difference in elderly patients with asthma. METHODS:
      The inhalation procedure was examined in 155 elderly patients with asthma (male:
      n=66, average age +/- standard deviation: 75.5+/-5.65 years old; female: n=89,
      average age +/- standard deviation: 78.7+/-6.87 years old) during a medical
      examination. RESULTS: For the three items that were common to all devices, the
      percentages of the 155 patients who could/could not perform the actions were
      examined by separate Fisher's exact tests for males and females. A statistically
      significant difference (P=0.007) was observed for "breath holding", and more
      females than males were not able to hold their breath. Although no significant
      difference was seen in the "accurate number of times of inhalation", females
      tended to not be able to inhale accurately compared to males (P=0.072).
      CONCLUSION: Our results suggest that elderly female patients with asthma have
      less understanding of inhaled steroid therapy, compared to elderly male patients.
      Therefore, it is particularly important to confirm that the correct inhalation
      procedure is used by elderly female patients with asthma.

PMID- 26300636
TI  - Comorbidities in obstructive lung disease in Korea: data from the fourth and
      fifth Korean National Health and Nutrition Examination Survey.
AB  - BACKGROUND: Comorbidities can occur frequently in patients with chronic
      obstructive pulmonary disease (COPD) and can influence mortality and morbidity
      independently. It is increasingly recognized that many patients with COPD have
      comorbidities that have a major impact on their quality of life and survival.
      Therefore, we investigated the prevalence of comorbidities in Korean COPD
      populations. METHODS: We used data obtained in the 6 years of the fourth and
      fifth Korean National Health and Nutrition Examination Survey (KNHANES) IV and V.
      Among 50,405 subjects, 16,151 subjects aged >=40 years who performed spirometry
      adequately were included in this study. Airway obstruction was defined as forced
      expiratory volume in 1 second/forced vital capacity <0.7, and the Global
      Initiative For Chronic Obstructive Lung Disease stage was used to evaluate the
      severity of airway obstruction. Statistical analyses were performed using SAS
      9.2. RESULTS: Among the 16,151 subjects (43.2% male, 56.8% female; mean age: 57.1
      years for men and 57.2 years for women), 13.1% had obstructive lung function;
      11.3%, restrictive lung function; and 75.6%, normal lung function. Among
      individuals with obstructive lung function, 45.3%, 49.4%, and 5.3% had mild,
      moderate, and severe and very severe airflow limitation. The prevalence of
      hypertension, diabetes mellitus (DM), underweight, and hypertriglyceridemia was
      higher in the obstructive lung function group than in the normal lung function
      group (49.6% vs 35.2%; 16.8% vs 10.5%; 3.3% vs 1.3%; 19.7% vs 17.0%). According
      to the severity of airway obstruction, hypertension and underweight were more
      common as severity increased, although the prevalence of DM and
      hypertriglyceridemia was lower in subjects with severe airway obstruction. The
      prevalence of hypercholesterolemia, overweight, and osteoarthritis was lower in
      the obstructive lung function group, especially in the severe airway obstruction
      groups. CONCLUSIONS: Overall, our analysis is similar to research that was
      conducted earlier. Our study showed that hypertension and underweight are common
      comorbidities in COPD patients, and are higher as the severity of airflow
      obstruction increased in both men and women. DM, hypertriglyceridemia, and low
      high-density lipoprotein cholesterol are more common in subjects with airway
      obstruction, although their incidence is lower in the severe group.

PMID- 26300637
TI  - Major affective disorders in chronic obstructive pulmonary disease compared with
      other chronic respiratory diseases.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) and other chronic
      respiratory diseases (CRDs) have significant impacts on quality of life including
      psychomotor domain. PURPOSE: To evaluate three major affective disorders in
      subjects with COPD compared with other CRDs and nonill population. MATERIALS AND
      METHODS: The Thai version of Mini International Neuropsychiatric Interview (MINI)
      was used as a diagnostic instrument for three major affective disorders
      (generalized anxiety disorder, major depressive disorder, and panic disorder) by
      face-to-face interview in assessing patients with CRDs [COPD, asthma, rhinasthma,
      all asthma (asthma and rhinasthma), and chronic rhinitis], and nonill subjects.
      Logistic regression analyses were used to determine the relation between major
      affective disorders and CRDs adjusting for age, sex, and disease severity.
      RESULTS: Major affective disorders were more prevalent in CRDs than nonill groups
      (adjusted OR =2.6 [95% CI, 1.8-3.9], P<0.001). COPD patients had significantly
      more generalized anxiety and panic disorder (adjusted OR =4.0 [95% CI, 1.4-11.9],
      P=0.011, and 4.4 [95% CI, 1.1-18.1], P=0.038, respectively) but not major
      depressive disorder (adjusted OR =2.7 [95% CI, 0.8-9.0, P=0.105]) than nonill
      group. Comparing with all asthma, COPD patients had lower occurrence of major
      depressive and panic disorders (adjusted OR =0.1 [95% CI, 0.0-0.4], P=0.002, and
      0.1 [95% CI, 0.0-0.9], P=0.043, respectively). There was no difference in major
      mood disorders in COPD, rhinasthma, and chronic rhinitis patients. Major
      affective disorders were not increased by disease severity in COPD. CONCLUSION:
      Major affective disorders were significantly higher in CRDs than nonill
      population. Generalized anxiety and panic disorders were significantly high in
      COPD patients. Moreover, major depressive and panic disorders in COPD were
      significantly lower than all asthma. The prevalence of major affective disorders
      may not be related to severity of COPD.

PMID- 26300638
TI  - Thiazolidinediones are associated with a reduced risk of COPD exacerbations.
AB  - BACKGROUND: Thiazolidinediones (TZDs) are oral antihyperglycemic medications that
      are selective agonists to peroxisome proliferator-activated receptor gamma and
      have been shown to have potent anti-inflammatory effects in the lung. OBJECTIVE:
      The purpose of this study was to assess whether exposure to TZDs is associated
      with a decreased risk of chronic obstructive pulmonary disease (COPD)
      exacerbation. METHODS: A cohort study was performed by collecting data on all US
      veterans with diabetes and COPD who were prescribed oral antihyperglycemic
      medications during from period of October 1, 2005 to September 30, 2007. Patients
      who had two or more prescriptions for TZDs were compared with patients who had
      two or more prescriptions for an alternative oral anti-hyperglycemic medication.
      Multivariable negative binomial regression was performed with adjustment for
      potential confounding factors. The primary outcome was COPD exacerbations,
      including both inpatient and outpatient exacerbations. RESULTS: We identified
      7,887 veterans who were exposed to TZD and 42,347 veterans who were exposed to
      non-TZD oral diabetes medications. COPD exacerbations occurred in 1,258 (16%) of
      the TZD group and 7,789 (18%) of the non-TZD group. In multivariable negative
      binomial regression, there was a significant reduction in the expected number of
      COPD exacerbations among patients who were exposed to TZDs with an incidence rate
      ratio of 0.86 (95% CI 0.81-0.92). CONCLUSION: Exposure to TZDs was associated
      with a small but significant reduction in risk for COPD exacerbation among
      diabetic patients with COPD.

PMID- 26300640
TI  - Nanostructured lipid system as a strategy to improve the anti-Candida albicans
      activity of Astronium sp.
AB  - The genus Astronium (Anacardiaceae) includes species, such as Astronium
      fraxinifolium, Astronium graveolens, and Astronium urundeuva, which possess anti
      inflammatory, anti-ulcerogenic, healing, and antimicrobial properties.
      Nanostructured lipid systems are able to potentiate the action of plant extracts,
      reducing the required dose and side effects and improving antimicrobial activity.
      This work aims to evaluate a nanostructured lipid system that was developed as a
      strategy to improve the anti-Candida albicans activity of hydroethanolic extracts
      of stems and leaves from Astronium sp. The antifungal activity against C.
      albicans (ATCC 18804) was evaluated in vitro by a microdilution technique. In
      addition to the in vitro assays, the Astronium sp. that showed the best
      antifungal activity and selectivity index was submitted to an in vivo assay using
      a model of vulvovaginal candidiasis infection. In these assays, the extracts were
      either used alone or were incorporated into the nanostructured lipid system
      (comprising 10% oil phase, 10% surfactant, and 80% aqueous phase). The results
      indicated a minimal inhibitory concentration of 125.00 ug/mL before incorporation
      into the nanostructured system; this activity was even more enhanced when this
      extract presented a minimal inhibitory concentration of 15.62 ug/mL after its
      incorporation. In vivo assay dates showed that the nanostructure-incorporated
      extract of A. urundeuva leaves was more effective than both the unincorporated
      extract and the antifungal positive control (amphotericin B). These results
      suggest that this nanostructured lipid system can be used in a strategy to
      improve the in vitro and in vivo anti-C. albicans activity of hydroethanolic
      extracts of Astronium sp. 

PMID- 26300639
TI  - Peptides and proteins used to enhance gold nanoparticle delivery to the brain:
      preclinical approaches.
AB  - An exciting and emerging field in nanomedicine involves the use of gold
      nanoparticles (AuNPs) in the preclinical development of new strategies for the
      treatment and diagnosis of brain-related diseases such as neurodegeneration and
      cerebral tumors. The treatment of many brain-related disorders with AuNPs, which
      possess useful physical properties, is limited by the blood-brain barrier (BBB).
      The BBB highly regulates the substances that can permeate into the brain.
      Peptides and proteins may represent promising tools to improve the delivery of
      AuNPs to the central nervous system (CNS). In this review, we summarize the
      potential applications of AuNPs to CNS disorders, discuss different strategies
      based on the use of peptides or proteins to improve the delivery of AuNPs to the
      brain, and examine the intranasal administration route, which bypasses the BBB.
      We also analyze the potential neurotoxicity of AuNPs and the perspectives and new
      challenges concerning the use of peptides and proteins to enhance the delivery of
      AuNPs to the brain. The majority of the work described in this review is in a
      preclinical stage of experimentation, or in select cases, in clinical trials in
      humans. We note that the use of AuNPs still requires substantial study before
      being translated into human applications. However, for further clinical research,
      the issues related to the potential use of AuNPs must be analyzed. 

PMID- 26300642
TI  - Relationship between cobalamin deficiency and delirium in elderly patients
      undergoing cardiac surgery.
AB  - BACKGROUND: Delirium is common after cardiac surgery and is independently
      associated with increased morbidity, mortality, prolonged hospital stays, and
      higher costs. Cobalamin (vitamin B12) deficiency is a common cause of
      neuropsychiatric symptoms and affects up to 40% of elderly people. The
      relationship between cobalamin deficiency and the occurrence of delirium after
      cardiac surgery has not been examined in previous studies. We examined the
      relationship between cobalamin deficiency and delirium in elderly patients
      undergoing coronary artery bypass grafting (CABG) surgery. MATERIAL AND METHODS:
      A total of 100 patients with cobalamin deficiency undergoing CABG were enrolled
      in this retrospective study. Control group comprised 100 patients without
      cobalamin deficiency undergoing CABG. Patients aged 65 years or over were
      included. Diagnosis of delirium was made using Intensive Care Delirium Screening
      Checklist. Delirium severity was measured using the Delirium Rating Scale-revised
      98. RESULTS: Patients with cobalamin deficiency had a significantly higher
      incidence of delirium (42% vs 26%; P=0.017) and higher delirium severity scores
      (16.5+/-2.9 vs 15.03+/-2.48; P=0.034) than patients without cobalamin deficiency.
      Cobalamin levels were significantly lower in patients with delirium than patients
      without delirium (P=0.004). Delirium severity score showed a moderate correlation
      with cobalamin levels (rho=-0.27; P=0.024). Logistic regression analysis
      demonstrated that cobalamin deficiency was independently associated with
      postoperative delirium (OR 1.93, 95% CI 1.03-3.6, P=0.038). CONCLUSION: The
      results of our study suggest that cobalamin deficiency may be associated with
      increased risk of delirium in patients undergoing CABG. In addition, we found
      that preoperative cobalamin levels were associated with the severity of delirium.
      This report highlights the importance of investigation for cobalamin deficiency
      in patients undergoing cardiac surgery, especially in the elderly.

PMID- 26300641
TI  - Caenorhabditis elegans as an alternative in vivo model to determine oral uptake,
      nanotoxicity, and efficacy of melatonin-loaded lipid-core nanocapsules on
      paraquat damage.
AB  - Caenorhabditis elegans is an alternative in vivo model that is being successfully
      used to assess the pharmacological and toxic effects of drugs. The exponential
      growth of nanotechnology requires the use of alternative in vivo models to assess
      the toxic effects of theses nanomaterials. The use of polymeric nanocapsules has
      shown promising results for drug delivery. Moreover, these formulations have not
      been used in cases of intoxication, such as in treatment of paraquat (PQ)
      poisoning. Thus, the use of drugs with properties improved by nanotechnology is a
      promising approach to overcome the toxic effects of PQ. This research aimed to
      evaluate the absorption of rhodamine B-labeled melatonin (Mel)-loaded lipid-core
      nanocapsules (LNC) by C. elegans, the application of this model in
      nanotoxicology, and the protection of Mel-LNC against PQ damage. The formulations
      were prepared by self-assembly and characterized by particle sizing, zeta
      potential, drug content, and encapsulation efficiency. The results demonstrated
      that the formulations had narrow size distributions. Rhodamine B-labeled Mel-LNC
      were orally absorbed and distributed in the worms. The toxicity assessment of LNC
      showed a lethal dose 50% near the highest dose tested, indicating low toxicity of
      the nanocapsules. Moreover, pretreatment with Mel-LNC significantly increased the
      survival rate, reduced the reactive oxygen species, and maintained the
      development in C. elegans exposed to PQ compared to those worms that were either
      untreated or pretreated with free Mel. These results demonstrated for the first
      time the uptake and distribution of Mel-LNC by a nematode, and indicate that
      while LNC is not toxic, Mel-LNC prevents the effects of PQ poisoning. Thus, C.
      elegans may be an interesting alternative model to test the nanocapsules toxicity
      and efficacy. 

PMID- 26300643
TI  - Relationship between cognitive insight and subjective quality of life in
      outpatients with schizophrenia.
AB  - BACKGROUND: The concept of cognitive insight refers to the cognitive processes
      involved in patients' re-evaluation of their anomalous experiences and of their
      misinterpretations. The purpose of the present study was to examine the
      relationship between cognitive insight and subjective quality of life in patients
      with schizophrenia to further shed light on the nature of cognitive insight and
      its functional correlates in schizophrenia. METHODS: Seventy-one stable
      outpatients with schizophrenia were evaluated for cognitive insight and
      subjective quality of life using the Beck Cognitive Insight Scale (BCIS) and the
      Schizophrenia Quality of Life Scale Revision 4 (SQLS-R4). The symptoms of
      schizophrenia were also assessed. Pearson's correlation analysis and partial
      correlation analysis that controlled for the severity of symptoms were performed
      to adjust for the possible effects of symptoms. RESULTS: The self-reflectiveness
      subscale score of the BCIS had significant positive correlations with the SQLS-R4
      psychosocial domain and total SQLS-R4 scores, indicating that the higher the
      level of cognitive insight, the lower the subjective quality of life. In partial
      correlation analysis controlling for symptoms, the BCIS self-reflectiveness
      subscale score still had a significant correlation with the SQLS-R4 psychosocial
      domain score. The correlation coefficient between the BCIS self-reflectiveness
      and total SQLS-R4 scores was reduced to a nonsignificant statistical tendency.
      CONCLUSION: The results of our study suggest that cognitive insight, particularly
      the level of self-reflectiveness, is negatively associated with the level of
      subjective quality of life in outpatients with schizophrenia and that this
      relationship is not wholly due to the confounding effect of symptoms. Future
      studies are necessary to explore possible mediating and moderating factors and to
      evaluate the effects of therapeutic interventions on the relationship.

PMID- 26300644
TI  - Adult attention-deficit hyperactivity disorder, risky behaviors, and motorcycle
      injuries: a case-control study.
AB  - BACKGROUND: The aim of this study was to assess the association of motorcycle
      traffic injuries with motorcycle riding behavior and subtypes of attention
      deficit hyperactivity disorder (ADHD) while controlling for individual correlates
      of motorcycle traffic injuries. METHODS: A case-control study was carried out in
      298 patients with motorcycle trauma along with 151 control patients admitted to
      the Shohada and Imam Reza university hospitals as the two referral specialty
      centers in the East Azarbyjan Province of Iran in 2013. The Persian version of
      the Motorcycle Riding Behavior Questionnaire and the Persian version of Conner's
      Adult ADHD Rating Scales (the self-report short version) were used to assess
      riding behavior and screen for adult ADHD, respectively. The scale has four
      subscales, comprising subscale A (inattention), subscale B (hyperactivity,
      impulsivity), subscale C (A + C), and subscale D (ADHD index). The statistical
      analysis was done using Stata version 11. RESULTS: All subjects were male and
      aged 13-79 years. Approximately 54% of the participants were married and 13% had
      academic education. Approximately 18% of the motorcycle riders stated that their
      motorcycle riding was only for fun purposes. More than two thirds of the
      participants did not have a motorcycle riding license. Variables found to be
      significantly associated with motorcycle injuries in bivariate analysis included
      age, marital status, educational level, having a motorcycle riding license, using
      a helmet while riding, daily amount of riding, riding just for fun, riding
      behavior score, and ADHD scale scores. It was found in multivariate analysis that
      if the ADHD index (subscale D) score was used to assess the association of ADHD
      with motorcycle injuries, a protective role for ADHD was observed. However, the
      two other subscales showed a different predictive pattern for subscale A versus
      subscale B, with only subscale B increasing the likelihood of motorcycle traffic
      injuries. The score based on motorcycle rider behavior was found to be associated
      with motorcycle injuries. Other variables that were significant in multivariate
      models were the purpose of riding, educational level, economic status, and
      marital status. CONCLUSION: ADHD and riding behavior scores affect the likelihood
      of motorcycle traffic injuries among motorcycle riders independent of other
      injury indicators, and include education, purpose of riding, and economic status.

PMID- 26300645
TI  - Combined application of eicosapentaenoic acid and docosahexaenoic acid on
      depression in women: a meta-analysis of double-blind randomized controlled
      trials.
AB  - OBJECTIVES: Previous randomized controlled trials (RCTs) suggest that depression
      can be effectively treated by omega-3 polyunsaturated fatty acids (PUFAs).
      Therefore, we conducted this meta-analysis to systematically evaluate the
      clinical applicability of the combination of docosahexaenoic acid (DHA) and
      eicosapentaenoic acid (EPA), which are the two major bioactive types of PUFAs, in
      depressed women. METHODS: RCTs that compared the combination of DHA and EPA to
      placebo for short-course treatment of depression in women were systematically
      reviewed up to March 2015. Outcome measurement was the standardized difference in
      means in clinical measure of depression severity. Random effect model was
      performed. Meta-regression analysis was performed to assess the effects of
      baseline depression scores. RESULTS: Data were obtained from eight RCTs. In these
      RCTs, 182 patients received placebo and 185 patients received DHA and EPA. The
      pooled standardized difference in mean was 0.65 with 95% CI = [0.18, 1.12]. There
      was no relation between the efficacy and the baseline depression scores. The
      sensitivity analysis found that the combination of EPA and DHA as monotherapy
      yielded a standardized difference in means of 0.65 (95% CI =0.41, 0.90) without
      heterogeneity. DISCUSSION: These results indicate a beneficial effect of the
      combination of EPA and DHA on depressed mood in women compared with placebo. The
      clinical applicability of EPA and DHA showed greater promise and should be
      further explored.

PMID- 26300646
TI  - Mental health status, aggression, and poor driving distinguish traffic offenders
      from non-offenders but health status predicts driving behavior in both groups.
AB  - BACKGROUND: In Iran, traffic accidents and deaths from traffic accidents are
      among the highest in the world, and generally, driver behavior rather than
      technical failures or environmental conditions are responsible for traffic
      accidents. In a previous study, we showed that among young Iranian male traffic
      offenders, poor mental health status, along with aggression, predicted poor
      driving behavior. The aims of the present study were twofold, to determine
      whether this pattern could be replicated among non-traffic offenders, and to
      compare the mental health status, aggression, and driving behavior of male
      traffic offenders and non-offenders. METHODS: A total of 850 male drivers (mean
      age =34.25 years, standard deviation =10.44) from Kermanshah (Iran) took part in
      the study. Of these, 443 were offenders (52.1%) and 407 (47.9%) were non
      offenders with lowest driving penalty scores applying for attaining an
      international driving license. Participants completed a questionnaire booklet
      covering socio-demographic variables, traits of aggression, health status, and
      driving behavior. RESULTS: Compared to non-offenders, offenders reported higher
      aggression, poorer mental health status, and worse driving behavior. Among non
      offenders, multiple regression indicated that poor health status, but not
      aggression, independently predicted poor driving behavior. CONCLUSION: Compared
      to non-offenders, offenders reported higher aggression, poorer health status and
      driving behavior. Further, the predictive power of poorer mental health status,
      but not aggression, for driving behavior was replicated for male non-offenders.

PMID- 26300648
TI  - Dynamic monitoring of plasma amino acids and carnitine during chemotherapy of
      patients with alimentary canal malignancies and its clinical value.
AB  - OBJECTIVE: The aim of this study was to observe the plasma amino acid and
      carnitine characteristics in patients with metastatic gastrointestinal
      malignancies during chemotherapy and to identify markers for the early diagnosis
      and evaluation of adverse reactions and prognosis of the digestive tract
      malignant tumor patients. METHODS: Blood samples of 30 patients with metastatic
      gastrointestinal malignancies were collected at four time points: before
      chemotherapy, the first day after chemotherapy (+1 day), bone marrow depression
      period (+14 days), and hematopoietic recovery period (+21 days). The plasma amino
      acids and carnitine from those 30 patients were determined by high-performance
      liquid chromatography-tandem mass spectrometry method. Simultaneously, the levels
      of 21 amino acids were detected in 30 healthy individuals, who were considered as
      control. Biochemical indexes were also detected at four time points, adverse
      reactions were recorded during the chemotherapy process, and patients were
      followed up for 1 year to observe time to progression (TTP) and progression-free
      survival (PFS). RESULTS: Compared to healthy people in the control group,
      patients with malignancies showed significantly increased levels of plasma amino
      acids such as Arg, Asp, Cit, Gly, Orn, Tyr, Val, and carnitine (such as C2). The
      levels of compounds such as C3, Asn, Leu, Lys, Pip, Pro, C0, C5:1 decreased
      significantly before chemotherapy. The levels of Cit, Cys, Lys, Pro, Tyr, Val,
      C0, and C2 decreased significantly on the second day of chemotherapy (+1 day),
      whereas the level of C3 increased significantly. During myelosuppression (+14
      days), the levels of Asp, Cit, Met, and Orn were observed to still decrease
      significantly, whereas the level of Val appeared to increase significantly. The
      levels of Asp, Glu, and Met were clearly different among patients with gastric
      carcinoma, rectal cancer, and colon cancer. Compared to the control group,
      aspartate amino transferase and alanine aminotransferase were found to be higher
      in eight patients with hypocarnitinemia, yet TTP, PFS, and RR (response rate)
      were lower. No significant difference was observed for adverse reactions. The
      indexes in 12 patients with citrullinemia showed no difference compared with
      control group. All the results showed statistically significant differences
      (P<0.05). CONCLUSION: Real-time monitoring of plasma amino acids and carnitine in
      patients with metastatic gastrointestinal malignancies can directly reflect the
      body's metabolism and nutritional status. The results provide a reference for
      nutrition therapy or support for patients with alimentary canal malignancies.
      Hypocarnitinemia is a risk factor for gastrointestinal cancer patients and
      affects TTP, PFS, and RR by liver function. This study shows that tandem mass
      spectrometry can be used to detect blood amino acids and carnitine spectrum may
      be used for an early diagnosis and evaluation of adverse reactions and prognosis
      of the digestive tract malignant tumor patients.

PMID- 26300649
TI  - PP4R1 accelerates cell growth and proliferation in HepG2 hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma (HCC), as the fifth most common cancer worldwide, has
      become the third leading cause of cancer-related deaths. It is reported that
      protein phosphatase 4 (PP4) is an essential protein for nucleation, growth, and
      stabilization of microtubules in centrosomes/spindle bodies during cell division.
      Besides, previous studies have identified protein phosphatase 4 regulatory
      subunit 1 (PP4R1) as a constitutive interaction partner of PP4 catalytic subunit
      PP4C. The PP4C-PP4R1 PP4 complex plays a role in dephosphorylation, regulation of
      histone acetylation, and NF-kappaB activation. However, little is known about the
      pathological functions of PP4R1 in human cancers. Thus, in order to investigate
      how PP4R1 functions in human HCC, two common hepatocarcinogenesis HCC cell lines
      HepG2 and SMMC-7721 were employed, transduced with recombinant lentivirus
      expressing PP4R1 short hairpin RNA. Compared with the controls, the cells treated
      with Lv-shPP4R1 showed a significant decrease in cell proliferation and colony
      formation. The results of flow cytometry showed that the knockdown of PP4R1
      caused HepG2 cells arrest at G2/M phase in the cell cycle. Furthermore, the
      transduction of Lv-shPP4R1 into HepG2 cells led to the inactivation of two major
      mitogen-activated protein kinase signaling cascades: p38 and c-Jun N-terminal
      kinase (JNK), indicating that PP4R1 could promote cell proliferation, which might
      be regulated by p38 and c-Jun N-terminal kinase pathways. In a word, this study
      highlights the crucial role of PP4R1 in promoting HCC cell growth, which might
      elucidate the pathological mechanism of HCC. 

PMID- 26300647
TI  - Secondary stroke prevention: challenges and solutions.
AB  - Stroke is the leading cause of disability in the USA and a major cause of
      mortality worldwide. One out of four strokes is recurrent. Secondary stroke
      prevention starts with deciphering the most likely stroke mechanism. In general,
      one of the main goals in stroke reduction is to control vascular risk factors
      such as hypertension, diabetes, dyslipidemia, and smoking cessation. Changes in
      lifestyle like a healthy diet and aerobic exercise are also recommended
      strategies. In the case of cardioembolism due to atrial fibrillation, mechanical
      valves, or cardiac thrombus, anticoagulation is the mainstay of therapy. The role
      of anticoagulation is less evident in the case of bioprosthetic valves, patent
      foramen ovale, and dilated cardiomyopathy with low ejection fraction. Strokes due
      to larger artery atherosclerosis account for approximately a third of all
      strokes. In the case of symptomatic extracranial carotid stenosis, surgical
      intervention as close as possible in time to the index event seems highly
      beneficial. In the case of intracranial large artery atherosclerosis, the best
      medical therapy consists of antiplatelets, high-dose statins, aggressive controls
      of vascular risk factors, and lifestyle modifications, with no role for
      intracranial arterial stenting or angioplasty. For patients with small artery
      occlusion (ie, lacunar stroke), the therapy is similar to that used in patients
      with intracranial large artery atherosclerosis. Despite the constant new evidence
      on how to best treat patients who have suffered a stroke, the risk of stroke
      recurrence remains unacceptably high, thus evidencing the need for novel
      therapies. 

PMID- 26300650
TI  - Outpatient parenteral antimicrobial therapy with ceftriaxone for acute
      tonsillopharyngitis: efficacy, patient satisfaction, cost effectiveness, and
      safety.
AB  - BACKGROUND: Outpatient parenteral antimicrobial therapy (OPAT) is the
      administration of intravenous antimicrobial therapy to patients in an outpatient
      setting. It may be used for patients who have infections that require parenteral
      treatment but who are otherwise stable enough to not require admission as
      inpatients. OBJECTIVE: We aimed to review the treatment of patients with acute
      tonsillopharyngitis at the OPAT health care clinic in the Bahrain Defense Force
      Royal Medical Services (BDF-RMS), with regard to efficacy, patient satisfaction,
      cost effectiveness, and safety. METHODS: A retrospective case notes review was
      conducted for all patients admitted to the OPAT clinic in the BDF-RMS with acute
      tonsillopharyngitis treated with ceftriaxone, between March 2012 and March 2014.
      RESULTS: In the period between March 2012 and March 2014, 97 patients with acute
      tonsillopharyngitis were treated with ceftriaxone for a minimum of 3 days at the
      OPAT clinic. In total, 94.8% of patients completed the prescribed course of
      ceftriaxone. Total cure was achieved in 89.7% of patients. Usage of the OPAT
      clinic led to cost savings of 10,693 BD, while total bed days saved were 301 over
      the 2-year period examined by this study. Participants in the program expressed
      high satisfaction rates, and the average (+/- standard deviation) score on a
      patient satisfaction survey was 4.41 (+/- 0.31) out of a total of 5. This study
      highlights the efficacy, patient satisfaction, cost effectiveness, and safety of
      the OPAT clinic service for the treatment of acute tonsillopharyngitis with
      ceftriaxone. We found a 45.5% drop in admission rate for acute
      tonsillopharyngitis after starting the OPAT service clinic and that 301 bed days
      were saved through this treatment. CONCLUSION: This study showed that the
      management of acute tonsillopharyngitis with ceftriaxone in the OPAT clinic is
      safe, clinically effective, and cost effective, with low rates of
      complications/readmissions and high levels of patient satisfaction.

PMID- 26300652
TI  - Associations between cardiovascular risk factors and psoriasis in Iran.
AB  - BACKGROUND: Psoriasis is a common chronic inflammatory skin disease. There is
      overwhelming evidence on the higher risk of cardiovascular diseases in patients
      with psoriasis as a result of hyperlipidemia, which is more common in these
      patients. OBJECTIVES: The aim of this study was to elucidate the association
      between the cardiovascular risk factors and psoriasis. METHODS: In a cross
      sectional study, 55 patients with psoriasis and 55 matched (sex and age) controls
      were entered the study at the Department of Dermatology between March 2011 and
      March 2013. Blood samples were obtained following 14 hours fasting status and
      serum levels of triglyceride, cholesterol, high-density lipoprotein, and low
      density lipoprotein were determined using standard laboratory methods, and other
      variables such as sex, age, smoking, alcohol consumption, and the type of disease
      were recorded. RESULTS: Our findings showed that levels of triglyceride, low
      density lipoprotein, and smoking were significantly higher in psoriatic patients
      when compared with controls, whereas the level of high-density lipoprotein and
      cholesterol was not significantly different between two groups. Body mass index
      of psoriatic patients was not significantly higher than controls. Patients with
      psoriasis also had an increased prevalence of hypertension. CONCLUSION: Our
      findings further verify lipid abnormalities in psoriatic patients. Psoriasis is
      associated with higher rate of hypertension, which may be resulted in increasing
      the risk of cardiovascular diseases in these patients. Thus, serum lipid profile
      and blood pressure in all patients with psoriasis, regardless of disease
      severity, deserve consideration to be checked.

PMID- 26300653
TI  - In vitro inhibition of hyaluronidase by sodium copper chlorophyllin complex and
      chlorophyllin analogs.
AB  - BACKGROUND: Inhibitors of hyaluronidase are potent agents that maintain
      hyaluronic acid homeostasis and may serve as anti-aging, anti-inflammatory, and
      anti-microbial agents. Sodium copper chlorophyllin complex is being used
      therapeutically as a component in anti-aging cosmeceuticals, and has been shown
      to have anti-hyaluronidase activity. In this study we evaluated various
      commercial lots of sodium copper chlorophyllin complex to identify the primary
      small molecule constituents, and to test various sodium copper chlorophyllin
      complexes and their small molecule analog compounds for hyaluronidase inhibitory
      activity in vitro. Ascorbate analogs were tested in combination with copper
      chlorophyllin complexes for potential additive or synergistic activity. MATERIALS
      AND METHODS: For hyaluronidase activity assays, dilutions of test materials were
      evaluated for hydrolytic activity of hyaluronidase by precipitation of non
      digested hyaluronate by measuring related turbidity at 595 nm. High-performance
      liquid chromatography and mass spectroscopy was used to analyze and identify the
      primary small molecule constituents in various old and new commercial lots of
      sodium copper chlorophyllin complex. RESULTS: The most active small molecule
      component of sodium copper chlorophyllin complex was disodium copper isochlorin
      e4, followed by oxidized disodium copper isochlorin e4. Sodium copper
      chlorophyllin complex and copper isochlorin e4 disodium salt had hyaluronidase
      inhibitory activity down to 10 ug/mL. The oxidized form of copper isochlorin e4
      disodium salt had substantial hyaluronidase inhibitory activity at 100 ug/mL but
      not at 10 ug/mL. Ascorbate derivatives did not enhance the hyaluronidase
      inhibitory activity of sodium copper chlorophyllin. Copper isochlorin e4 analogs
      were always the dominant components of the small molecule content of the
      commercial lots tested; oxidized copper isochlorin e4 was found in increased
      concentrations in older compared to newer lots tested. CONCLUSION: These results
      support the concept of using the hyaluronidase inhibitory activity of sodium
      copper chlorophyllin complex to increase the hyaluronic acid level of the dermal
      extracellular matrix for the improvement of the appearance of aging facial skin.

PMID- 26300651
TI  - Bloodstream infections in intensive care unit patients: distribution and
      antibiotic resistance of bacteria.
AB  - Bloodstream infections (BSIs) are among the leading infections in critically ill
      patients. The case-fatality rate associated with BSIs in patients admitted to
      intensive care units (ICUs) reaches 35%-50%. The emergence and diffusion of
      bacteria with resistance to antibiotics is a global health problem. Multidrug
      resistant bacteria were detected in 50.7% of patients with BSIs in a recently
      published international observational study, with methicillin resistance detected
      in 48% of Staphylococcus aureus strains, carbapenem resistance detected in 69% of
      Acinetobacter spp., in 38% of Klebsiella pneumoniae, and in 37% of Pseudomonas
      spp. Prior hospitalization and antibiotic exposure have been identified as risk
      factors for infections caused by resistant bacteria in different studies.
      Patients with BSIs caused by resistant strains showed an increased risk of
      mortality, which may be explained by a higher incidence of inappropriate
      empirical therapy in different studies. The molecular genetic characterization of
      resistant bacteria allows the understanding of the most common mechanisms
      underlying their resistance and the adoption of surveillance measures. Knowledge
      of epidemiology, risk factors, mechanisms of resistance, and outcomes of BSIs
      caused by resistant bacteria may have a major influence on global management of
      ICU patients. The aim of this review is to provide the clinician an update on
      BSIs caused by resistant bacteria in ICU patients. 

PMID- 26300655
TI  - Development of opioid-induced constipation: post hoc analysis of data from a 12
      week prospective, open-label, blinded-endpoint streamlined study in low-back pain
      patients treated with prolonged-release WHO step III opioids.
AB  - BACKGROUND: Opioid-induced constipation is the most prevalent patient complaint
      associated with longer-term opioid use and interferes with analgesic efficacy,
      functionality, quality of life, and patient compliance. OBJECTIVES: We aimed to
      compare the effects of prolonged-release (PR) oxycodone plus PR naloxone (OXN) vs
      PR oxycodone (OXY) vs PR morphine (MOR) on bowel function under real-life
      conditions in chronic low-back pain patients refractory to World Health
      Organization (WHO) step I and/or II analgesics. RESEARCH DESIGN AND METHODS: This
      was a post hoc analysis of the complete data set from a prospective, randomized,
      open-label, blinded endpoint (PROBE) streamlined study (German pain study
      registry: 2012-0012-05; European Union Drug Regulating Authorities Clinical
      Trials [EudraCT]: 2012-001317-16), carried out in 88 centers in Germany, where a
      total of 901 patients requiring WHO step III opioids to treat low-back pain were
      enrolled and prospectively observed for 3 months. Opioid allocation was based on
      either optional randomization (n=453) or physician decision (n=448). In both
      groups, treatment doses could be adjusted as per the German prescribing
      information, and physicians were free to address all side effects and
      tolerability issues as usual. The primary endpoint was the proportion of patients
      maintaining normal bowel function throughout the complete treatment period,
      assessed with the Bowel Function Index (BFI). Secondary analyses addressed
      absolute and relative BFI changes, complete spontaneous bowel movements, use of
      laxatives, treatment emergent adverse events, analgesic effects, and differences
      between randomized vs nonrandomized patient groups. RESULTS: BFI changed
      significantly with all three WHO step III treatments, however significantly less
      with OXN vs OXY and MOR despite a significantly higher use of laxatives with the
      latter ones (P<0.001). The percentage of patients who maintained normal BFI
      scores despite opioid treatment was 54.5% (164/301) with OXN and was
      significantly superior to those seen with OXY (32.8% [98/300]) (odds ratio [OR]:
      2.47, 95% confidence interval [CI]: 1.77-3.44; P<0.001) or MOR (29.7% [89/300])
      (OR: 2.84, 95% CI: 2.03-3.97; P<0.001). Absolute BFI changes of >=12mm 100 mm
      horizontal visual analog scale (VAS100) vs. baseline were seen for OXN in 41.4%,
      for OXY in 68.7%, and for MOR in 72.3%. Complete spontaneous bowel movements
      decreased at least by one per week in 10.3% with OXN vs 42.3% for OXY (OR: 6.39,
      95% CI 4.13-9.89; P<0.001) and 42.0% for MOR (OR: 6.31, 95% CI: 4.08-9.76;
      P<0.001). Overall, 359 treatment emergent adverse events (78 [OXN], 134 [OXY],
      and 147 [MOR]) in 204 patients (41 [OXN], 80 [OXY], and 83 [MOR]) occurred, most
      affecting the gastrointestinal (49.3%) and the nervous system (39.3%). Treatment
      contrasts between randomized vs nonrandomized patients were insignificant.
      CONCLUSION: In this post hoc analysis of data from a real-life 12-week study, OXN
      treatment was associated with a significantly lower risk of opioid-induced
      constipation, superior tolerability, and significantly better analgesic efficacy
      compared with OXY and MOR.

PMID- 26300654
TI  - Pulmonary capillary hemangiomatosis: a focus on the EIF2AK4 mutation in onset and
      pathogenesis.
AB  - Pulmonary capillary hemangiomatosis (PCH) is a pulmonary vascular disease that
      mainly affects small capillaries in the lung, and is often misdiagnosed as
      pulmonary arterial hypertension or pulmonary veno-occlusive disease due to
      similarities in their clinical presentations, prognosis, and management. In
      patients who are symptomatic, there is a high mortality rate with median survival
      of 3 years after diagnosis. Both idiopathic and familial PCH cases are being
      reported, indicating there is genetic component in disease etiology. Mutations in
      the eukaryotic translation initiation factor 2alpha kinase 4 (EIF2AK4) gene were
      identified in familial and idiopathic PCH cases, suggesting EIF2AK4 is a genetic
      risk factor for PCH. EIF2AK4 mutations were identified in 100% (6/6) of autosomal
      recessively inherited familial PCH and 20% (2/10) of sporadic PCH cases. EIF2AK4
      is a member of serine/threonine kinases. It downregulates protein synthesis in
      response to a variety of cellular stress such as hypoxia, viral infection, and
      amino acid deprivation. Bone morphogenetic protein receptor 2 (BMPR2) is a major
      genetic risk factor in pulmonary arterial hypertension and EIF2AK4 potentially
      connects with BMPR2 to cause PCH. L-Arginine is substrate of nitric oxide
      synthase, and L-arginine is depleted during the production of nitric oxide, which
      may activate EIF2AK4 to inhibit protein synthesis and negatively regulate
      vasculogenesis. Mammalian target of rapamycin and EIF2alpha kinase are two major
      pathways for translational regulation. Mutant EIF2AK4 could promote proliferation
      of small pulmonary arteries by crosstalk with mammalian targets of the rapamycin
      signaling pathway. EIF2AK4 may regulate angiogenesis by modulating the immune
      system in PCH pathogenesis. The mechanisms of abnormal capillary angiogenesis are
      suggested to be similar to that of tumor vascularization. Specific therapies were
      developed according to pathogenesis and are proved to be effective in reported
      cases. Targeting the EIF2AK4 pathway may provide a novel therapy for PCH. 

PMID- 26300656
TI  - Self-reported nonrestorative sleep in fibromyalgia - relationship to impairments
      of body functions, personal function factors, and quality of life.
AB  - PURPOSE: The purpose of this study was: 1) to determine variables that might
      characterize good or bad sleep; and 2) to describe the relationship between
      sleep, impairment of body functions, personal function factors, and quality of
      life based on quality of sleep in women with fibromyalgia (FM). METHODS: This
      cross-sectional descriptive study included 224 consecutive patients diagnosed at
      a specialist center. These patients were mailed a questionnaire concerning sleep,
      body functions, personal factors, and health-related quality of life. In total,
      145 completed questionnaires were collected. RESULTS: Using sleep variables
      (sleep quality, waking up unrefreshed, and tiredness when getting up), we
      identified two subgroups - the good sleep subgroup and the bad sleep subgroup -
      of women with FM. These subgroups exhibited significantly different
      characteristics concerning pain intensity, psychological variables (depressed
      mood, anxiety, catastrophizing, and self-efficacy), impairments of body
      functions, and generic and health-related quality of life. The good sleep
      subgroup reported a significantly better situation, including higher
      employment/study rate. The bad sleep subgroup reported a greater use of sleep
      medication. Five variables determined inclusion into either a good sleep or a bad
      sleep subgroup: pain in the evening, self-efficacy, anxiety, and according to the
      Short Form health survey role emotional and physical functioning. CONCLUSION:
      This study found that it was possible to identify two subgroups of women with FM
      based on quality of sleep variables. The two subgroups differed significantly
      with respect to pain, psychological factors, impairments of body functions, and
      perceived quality of life, where the subgroup with bad sleep had a worse
      situation.

PMID- 26300657
TI  - Establishment and characterization of a receptor-negative, hormone-nonresponsive
      breast cancer cell line from an Iraqi patient.
AB  - A new breast cancer cell line (AMJ13) has been established from an Iraqi breast
      cancer patient. It is considered unique because it is the first for an Iraqi
      population, and is expected to be a useful tool in breast cancer research. The
      AMJ13 cell line was established from the primary tumor of a 70-year-old Iraqi
      woman with a histological diagnosis of infiltrating ductal carcinoma. The cells
      were morphologically characterized by light and scanning electron microscopy, and
      found to be elongated multipolar epithelial-like cells with a population doubling
      time of 22 hours. The anchorage-independent growth ability test showed that the
      cells were able to grow in semisolid agarose, confirming their transformed
      nature. Cytogenetic study of these cells showed chromosomal aberrations with many
      structural and numerical abnormalities, producing chromosomes of unknown origin
      called marker chromosomes. Immunocytochemistry showed that the estrogen receptor
      and the progesterone receptor were not expressed, and a weak positive result was
      found for HER2/neu gene expression. AMJ13 cells were positive for BRCA1 and
      BRCA2, as well as for vimentin. This cell line should be useful when testing new
      therapies for breast cancer in the Middle East. 

PMID- 26300658
TI  - The impact of transitioning from a 24-hour to a 16-hour call model amongst a
      cohort of Canadian anesthesia residents at McMaster University - a survey study.
AB  - PURPOSE: The primary objective of this study was to assess anesthesia residents'
      opinions and perceptions on wellness/burnout, fatigue, education, and patient
      safety after the initiation of a reduced call model (16-hour call). METHODS: A
      prospective cohort study was conducted at three time points during the 2013-2014
      academic year. A web-based questionnaire consisting of 23 questions was
      electronically distributed to all anesthesia residents from postgraduate years
      (PGY) 1 to 5 who were part of the active call roster (n=84) at McMaster
      University in Hamilton, Ontario. Descriptive summaries were calculated, counts
      and percentages were used for categorical variables, and answers to open text
      questions were reviewed for themes. RESULTS: A response rate of 67% was obtained
      for this study. A majority of anesthesia residents (65%) approved of 16-hour
      call, felt that their overall quality of life as a senior resident (PGY3 or
      greater) or junior resident (PGY2 and below) had improved (73% and 55%,
      respectively), and reported overall feeling less fatigued. Most respondents
      indicated that the quality of education remained unchanged (47%), or had improved
      (31%). And most felt better prepared for the royal college exam (52%). Most felt
      patient safety had improved or was unchanged (both 48%). CONCLUSION: The study
      demonstrates that 16-hour call improved resident wellness, reduced burnout and
      fostered an environment where residents are less fatigued and more satisfied with
      their educational experience promoting an environment of patient safety. Overall,
      the anesthesia residency group demonstrated that not only is 16-hour call
      preferred but beneficial.

PMID- 26300659
TI  - Incorporating medical leadership and management into the UK undergraduate medical
      curriculum.

PMID- 26300660
TI  - Ready or not? Lung cancer diagnosis in 2015.

PMID- 26300661
TI  - Enhancing access to cancer care for the Inuit.

PMID- 26300662
TI  - A retrospective review of cancer treatments and outcomes among Inuit referred
      from Nunavut, Canada.
AB  - BACKGROUND: Cancer is a health concern in Inuit populations. Unique cultural,
      dietary, and genetic factors and geographic isolation influence cancer
      epidemiology in this group. Inuit-specific data about oncology treatments and
      survival outcomes in Canadian Inuit referred to urban treatment centres are
      lacking. METHODS: A retrospective chart review of Inuit patients referred to The
      Ottawa Hospital Cancer Centre (tohcc) from the Baffin region of Nunavut between
      2000 and 2010 was conducted. Nunavut cancer registry data were used to establish
      the percentage of cancer cases referred and their survival outcomes. RESULTS: Of
      307 cancer patients registered among Baffin-region Inuit, 216 [70% (63 men, 153
      women)] were referred to tohcc for chemotherapy (ct) and radiation therapy (rt).
      Mean age in the referred group was 59.3 years (range: 25-89 years), and current
      smokers constituted half the group (52%). The cancers most commonly leading to
      referral in men were lung (55%), colorectal (19%), and nasopharyngeal (11%)
      cancers; in women, they were lung (46%), colorectal (24%), breast (10%),
      nasopharyngeal (6%), and cervical (5%) cancers. Of the 216 referred patients, 82
      (38%) had already undergone surgery, and 18 (8%) received chemoradiation or rt
      only, all given with curative intent. Among the surgical patients referred, 33
      (40%) and 23 (28%) went on to receive adjuvant ct and adjuvant rt respectively.
      Among 116 patients referred for palliative care, 64 (55%) received ct, 76 (66%)
      received rt, 43 (37%) received both ct and rt, and 19 (16%) received neither
      treatment. Median all-stage overall survival was 10 months for patients with lung
      cancer [95% confidence interval: 6.1 to 13.9 months] and 37 months for patients
      with colorectal cancer [95% confidence interval: 14.8 to 59.2 months].
      CONCLUSIONS: High uptake of palliative and adjuvant ct and rt was observed in the
      Inuit patients referred to tohcc. Lung cancer was the most common cancer in
      referred Inuit men and women. The survival rates for Inuit lung cancer patients
      referred to tohcc were comparable to those in the rest of Canada. Further
      research is required to understand reasons for non-referral of Canadian Inuit to
      tohcc.

PMID- 26300663
TI  - Views of family physicians about survivorship care plans to provide breast cancer
      follow-up care: exploration of results from a randomized controlled trial.
AB  - BACKGROUND: The U.S. Institute of Medicine recommends that cancer patients
      receive survivorship care plans, but evaluations to date have found little
      evidence of the effectiveness of such plans. We conducted a qualitative follow-on
      study to a randomized controlled trial (rct) to understand the experiences of
      family physicians using survivorship care plans to support the follow-up of
      breast cancer patients. METHODS: A subset of family physicians whose patients
      were enrolled in the parent rct in Ontario and Nova Scotia were eligible for this
      study. In interviews, the physicians discussed survivorship care plans
      (intervention) or usual discharge letters (control), and their confidence in
      providing follow-up cancer care. RESULTS: Of 123 eligible family physicians, 18
      (10 intervention, 8 control) were interviewed. In general, physicians receiving a
      survivorship care plan found only the 1-page care record to be useful. Physicians
      who received only a discharge letter had variable views about the letter's
      usefulness; several indicated that it lacked information about potential cancer-
      or treatment-related problems. Most physicians were comfortable providing care 3
      5 years after diagnosis, but desired timely and informative communication with
      oncologists. CONCLUSIONS: Although family physicians did not find extensive
      survivorship care plans useful, discharge letters might not be sufficiently
      comprehensive for follow-up breast cancer care. Effective strategies for two-way
      communication between family physicians and oncologists are still lacking.

PMID- 26300664
TI  - An open-label expanded-access trial of bendamustine in patients with rituximab
      refractory indolent non-Hodgkin lymphoma or previously untreated chronic
      lymphocytic leukemia: BEND-ACT.
AB  - BACKGROUND: Bendamustine is a bifunctional alkylating agent with unique
      properties that distinguish it from other agents in its class. Bendamustine is
      used as monotherapy or in combination with other agents to treat patients with
      non-Hodgkin lymphoma (nhl) and chronic lymphocytic leukemia (cll). METHODS: The
      prospective interventional open-label bend-act trial evaluated bendamustine in
      patients with rituximab-refractory indolent nhl (inhl) and previously untreated
      cll. Study objectives were to assess the safety and tolerability of bendamustine
      monotherapy and to provide patients with access to bendamustine before Health
      Canada approval. The study aimed to enrol up to 100 patients. All patients with
      inhl received an intravenous dose of bendamustine 120 mg/m(2) over 60 minutes on
      days 1 and 2 for up to eight 21- or 28-day treatment cycles. All patients with
      cll received an intravenous dose of bendamustine 100 mg/m(2) over 30 minutes on
      days 1 and 2 for up to six 28-day treatment cycles. RESULTS: Of 90 patients
      treated on study (16 with cll and 74 with inhl), 35 completed the study (4 with
      cll and 31 with inhl). The most common treatment-emergent adverse events (teaes)
      were nausea (70%), fatigue (57%), vomiting (40%), and diarrhea (33%)-mostly
      grades 1 and 2. Ondansetron was the most common supportive medication used in the
      patients (63.5% of those with inhl and 68.8% of those with cll). Neutropenia
      (32%), anemia (23%), and thrombocytopenia (21%) were the most frequent
      hematologic teaes, with neutropenia being the most common grade 3 or 4 teae
      leading to dose modification. Dose delays occurred in 28 patients (31.3%) because
      of grade 3 or 4 teaes, with a higher incidence of dose delays being observed in
      inhl patients on the 21-day treatment cycle than in those on the 28-day treatment
      cycle (50.0% vs. 24.1%). During the study, 33 patients (36.7%) experienced at
      least 1 serious adverse event, and 4 deaths were reported (all in patients with
      inhl). CONCLUSIONS: The type and frequency of the teaes reported accorded with
      observations in earlier clinical trials and post-marketing experiences, thus
      confirming the acceptable and manageable safety profile of bendamustine.

PMID- 26300665
TI  - Diagnosing lung cancer in the 21st century: are we ready to meet the challenge of
      individualized care?
AB  - BACKGROUND: Histologic and molecular subtyping have become increasingly important
      as predictors of treatment benefit in lung cancer. The objective of the present
      study was to determine whether current diagnostic approaches provide adequate
      tissue to allow for individualized treatment decisions. METHODS: Our
      retrospective cohort study of new lung cancer patients seen at an academic centre
      between July 2007 and June 2008 collected baseline demographic and diagnostic
      information, including mode of diagnosis, type of diagnostic material, and
      pathology diagnosis. RESULTS: Of the 431 study patients, 20% had stage i or ii
      non-small-cell lung cancer (nsclc), 24% stage iii disease, and 39% stage iv
      nsclc. Three quarters of the small-cell lung cancer (sclc) cases were extensive
      stage. Diagnostically, 18% of patients had sclc; 30%, adenocarcinoma; 27%,
      squamous-cell cancer; 2%, large-cell carcinoma; 1%, bronchoalveolar carcinoma;
      1%, mixed histology; 18%, nsclc not otherwise specified; 4%, other; and 2%, no
      pathology diagnosis. Surgical pathology material was available in 80% of cases,
      and cytology material alone in 20%. Surgical pathology material was more common
      in patients with early-stage than with advanced disease (89% for stages i and ii
      vs. 74% for stages iii and iv, p < 0.0001). The pathology report included
      ambiguous terms in 24% of cases: "consistent" (12%), "suspicious" (3%), "favour"
      (2%), "suggestive" (2%), "likely" (1%), "compatible" with malignancy (1%), "at
      least" (1%), "atypical" (0.5%), and "no pathology" (1.5%). CONCLUSIONS: Current
      diagnostic approaches in most lung cancer patients appear adequate, but complete
      histopathologic identification is missing in nearly 20% of cases, and some
      uncertainty as to the final diagnosis is expressed in 24% of pathology reports.
      Some improvement in diagnostic sampling and pathology reporting are required to
      allow for implementation of current treatment approaches.

PMID- 26300666
TI  - Patient preferences for timing and access to radiation therapy.
AB  - PURPOSE: Patient preferences for radiation therapy (rt) access were investigated.
      METHODS: Patients completing a course of rt at 6 centres received a 17-item
      survey that rated preferences for time of day; day of week; actual, ideal, and
      reasonable travel times for rt; and actual, ideal, and reasonable times between
      referral and first oncologic consultation. Patients receiving single-fraction rt
      or brachytherapy alone were excluded. RESULTS: Of the respondents who returned
      surveys (n = 1053), 54% were women, and 74% had received more than 15 rt
      fractions. With respect to appointment times, 88% agreed or strongly agreed that
      rt between 08h00 and 16h30 was preferred; 14%-15% preferred 07h30-08h00 or 16h30
      17h00; 10% preferred 17h00-18h00; and 6% or fewer preferred times before 07h30 or
      after 18h00. A preference not to receive rt before 07h30 or after 18h00 was
      expressed by 30% or more of the respondents. When days of the week were
      considered, 18% and 11% would have preferred to receive rt on a Saturday or
      Sunday respectively; 52% and 55% would have preferred not to receive rt on those
      days. A travel time of 1 hour or less for rt was reported by 82%, but 61% felt
      that a travel time of 1 hour or more was reasonable. A first consultation within
      2 weeks of referral was felt to be ideal or reasonable by 88% and 73% of patients
      respectively. CONCLUSIONS: An rt service designed to meet patient preferences
      would make most capacity available between 08h00 and 16h30 on weekdays and
      provide 10%-20% of rt capacity on weekends and during 07h30-08h00 and 16h30-18h00
      on weekdays. Approximately 80%, but not all, of the responding patients preferred
      a 2-week or shorter interval between referral and first oncologic consultation.

PMID- 26300667
TI  - The organization of colposcopy services in Ontario: recommended framework.
AB  - OBJECTIVE: The purpose of this guideline is to help ensure the provision of high
      quality colposcopy practices in the province of Ontario, including those
      conducted as diagnostic procedures in follow-up to an abnormal cervical screening
      test. METHODS: This document updates the recommendations published in the 2008
      colposcopy guideline from Cancer Care Ontario, The Optimum Organization for the
      Delivery of Colposcopy Service in Ontario. A systematic review of guidelines was
      conducted to evaluate the existing evidence and recommendations concerning these
      key aspects of colposcopy: ? Training, qualification, accreditation, and
      maintenance of competence? Practice setting requirements? Operational practice?
      Quality indicators and outcomes. RESULTS: This guideline provides recommendations
      on training and maintenance of competence for colposcopists in the practice
      settings in which colposcopic evaluation and treatments are conducted. It also
      provides recommendations on operational issues and quality indicators for
      colposcopy. CONCLUSIONS: This updated guideline is intended to support quality
      improvement for colposcopy for all indications, including the follow-up of an
      abnormal cervical screening test and work-up for lower genital tract lesions that
      are not clearly malignant. The recommendations contained in this document are
      intended for clinicians and institutions performing colposcopy in Ontario, and
      for policymakers and program planners involved in the delivery of colposcopy
      services.

PMID- 26300668
TI  - Recent trends in breast, cervical, and colorectal cancer screening test
      utilization in Canada, using self-reported data from 2008 and 2012.
AB  - In Canada, self-reported data from the Canadian Community Health Survey 2008 and
      2012 provide an opportunity to examine overall utilization of breast, cervical,
      and colorectal cancer screening tests for both programmatic and opportunistic
      screening. Among women 50-74 years of age, utilization of screening mammography
      was stable (62.0% in 2008 and 63.0% in 2012). Pap test utilization for women 25
      69 years of age remained high and stable across Canada in 2008 and 2012 (78.9% in
      2012). The percentage of individuals 50-74 years of age who reporting having at
      least 1 fecal test within the preceding 2 years increased in 2012 (to 23.0% from
      16.9% in 2008), but remains low. Stable rates of screening mammography
      utilization (about 30%) were reported in 2008 and 2012 among women 40-49 years of
      age, a group for which population-based screening is not recommended. Although
      declining over time, cervical cancer screening rates were high for women less
      than 25 years of age (for whom screening is not recommended). Interestingly, an
      increased percentage of women 70-74 years of age reported having a Pap test. In
      2012, a smaller percentage of women 50-69 years of age reported having no
      screening test (5.9% vs. 8.5% in 2008), and more women reported having the three
      types of cancer screening tests (19.0% vs. 13.2%). Efforts to encourage use of
      screening within the recommended average-risk age groups are needed, and
      education for stakeholders about the possible harms of screening outside those
      age groups has to continue. 

PMID- 26300669
TI  - Dasatinib for a child with Philadelphia chromosome-positive acute lymphoblastic
      leukemia and persistently elevated minimal residual disease during imatinib
      therapy.
AB  - Imatinib has improved outcomes in patients with Philadelphia chromosome-positive
      (Ph+) acute lymphoblastic leukemia (all). Minimal residual disease (mrd) is a
      useful tool for predicting leukemia relapse. However, there is no consensus on
      how to treat children with elevation of BCR-ABL transcripts but no evidence of
      hematologic relapse during chemotherapy combined with imatinib. Here, we report
      the case of a child with Ph+ all who had persistent elevation of mrd, but no
      evidence of hematologic relapse while receiving imatinib plus intensive
      chemotherapy. Dasatinib was substituted for imatinib because no suitable donor
      for allogeneic hematopoietic stem-cell transplantation (hsct) was available. Less
      intensive chemotherapy with methotrexate and 6-mercaptopurine was administered
      concomitantly. No serious adverse events were encountered. With continuous
      dasatinib combined with chemotherapy, but no allogeneic hsct, our patient reached
      complete molecular remission and has been in complete molecular remission for
      more than 13 months. This report is the first about the long-term use of
      dasatinib in patients with Ph+ all and mrd elevation but hematologic remission
      during imatinib chemotherapy. In a similar situation, chemotherapy combined with
      dasatinib instead of allogeneic hsct could be considered to avoid hsct-related
      mortality and morbidity. Clinical trials are needed. 

PMID- 26300670
TI  - BRCA1/2 population screening: embracing the benefits.

PMID- 26300671
TI  - Professionalism.

PMID- 26300672
TI  - Is it time to offer BRCA1 and BRCA2 testing to all Jewish women?

PMID- 26300673
TI  - Advance care planning: identifying system-specific barriers and facilitators.
AB  - BACKGROUND: Advance care planning (acp) is an important process in health care
      today. How to prospectively identify potential local barriers and facilitators to
      uptake of acp across a complex, multi-sector, publicly funded health care system
      and how to develop specific mitigating strategies have not been well
      characterized. METHODS: We surveyed a convenience sample of clinical and
      administrative health care opinion leaders across the province of Alberta to
      characterize system-specific barriers and facilitators to uptake of acp. The
      survey was based on published literature about the barriers to and facilitators
      of acp and on the Michie Theoretical Domains Framework. RESULTS: Of 88 surveys,
      51 (58%) were returned. The survey identified system-specific barriers that could
      challenge uptake of acp. The factors were categorized into four main domains.
      Three examples of individual system-specific barriers were "insufficient public
      engagement and misunderstanding," "conflict among different provincial health
      service initiatives," and "lack of infrastructure." Local system-specific
      barriers and facilitators were subsequently explored through a semi-structured
      informal discussion group involving key informants. The group identified
      approaches to mitigate specific barriers. CONCLUSIONS: Uptake of acp is a
      priority for many health care systems, but bringing about change in multi-sector
      health care systems is complex. Identifying system-specific barriers and
      facilitators to the uptake of innovation are important elements of successful
      knowledge translation. We developed and successfully used a simple and
      inexpensive process to identify local system-specific barriers and enablers to
      uptake of acp, and to identify specific mitigating strategies.

PMID- 26300674
TI  - Cost-utility of adjuvant zoledronic acid in patients with breast cancer and low
      estrogen levels.
AB  - BACKGROUND: Adjuvant zoledronic acid (za) appears to improve disease-free
      survival (dfs) in women with early-stage breast cancer and low levels of estrogen
      (lle) because of induced or natural menopause. Characterizing the cost-utility
      (cu) of this therapy could help to determine its role in clinical practice.
      METHODS: Using the perspective of the Canadian health care system, we examined
      the cu of adjuvant endocrine therapy with or without za in women with early-stage
      endocrine-sensitive breast cancer and lle. A Markov model was used to compute the
      cumulative costs in Canadian dollars and the quality-adjusted life-years (qalys)
      gained from each adjuvant strategy, discounted at a rate of 5% annually. The
      model incorporated the dfs and fracture benefits of adjuvant za. Probabilistic
      and one-way sensitivity analyses were conducted to examine key model parameters.
      RESULTS: Compared with a no-za strategy, adjuvant za in the induced and natural
      menopause groups was associated with, respectively, $7,825 and $7,789 in
      incremental costs and 0.46 and 0.34 in qaly gains for cu ratios of $17,007 and
      $23,093 per qaly gained. In one-way sensitivity analyses, the results were most
      sensitive to changes in the za dfs benefit. Probabilistic sensitivity analysis
      suggested a 100% probability of adjuvant za being a cost-effective strategy at a
      threshold of $100,000 per qaly gained. CONCLUSIONS: Based on available data,
      adjuvant za appears to be a cost-effective strategy in women with endocrine
      sensitive breast cancer and lle, having cu ratios well below accepted thresholds.

PMID- 26300675
TI  - Relationships between patient knowledge and the severity of side effects, daily
      nutrient intake, psychological status, and performance status in lung cancer
      patients.
AB  - AIM: We aimed to assess the relationships of patient education with the severity
      of treatment-induced side effects, daily calorie and protein intake,
      psychological status, and performance status in patients with lung cancer.
      METHODS: The study patients were divided into an intervention (n = 62) and a
      control group (n = 110). The patients in the intervention group were provided
      with information about treatment, diet, and rehabilitation during chemotherapy.
      The patients in the control group were not specially provided with that
      information. RESULTS: We observed significant differences between the
      intervention and control groups with respect to low daily protein intake (54.84%
      vs. 70.00%, p = 0.046), prevalence of depression (51.61% vs. 70.91%, p = 0.011),
      prevalence of severe side effects of treatment (14.52% vs. 37.27%, p = 0.002),
      and good performance status (75.81% vs. 55.45%, p = 0.008). CONCLUSIONS: Our
      results suggest that educating patients about cancer treatment and rehabilitation
      can lead to increased protein intake, a lower prevalence of depression, lesser
      side effects from cancer treatments, and improved performance status.

PMID- 26300676
TI  - In serum, higher parathyroid hormone but not lower vitamin D is associated with
      oral squamous cell carcinoma.
AB  - INTRODUCTION: Vitamin D and calcium are known to regulate differentiation and
      proliferation of keratinocytes; they might potentially have a role in suppressing
      carcinogenesis in squamous epithelium. Serum parathyroid hormone (pth) is a
      sensitive indicator of calcium and vitamin D deficiency, and 25-hydroxyvitamin D
      [25(OH)D] is an established marker of vitamin D status. METHODS: To determine
      whether levels of 25(OH)D, calcium, or pth in serum are associated with oral
      squamous cell carcinoma (oscc), we examined those parameters in serum collected
      from 70 patients with oscc and from an equal number of matched control subjects.
      RESULTS: The results showed that intact pth was significantly higher in serum
      from oscc patients than in serum from control subjects. However, we observed no
      significant differences in 25(OH)D or calcium in serum from oscc patients and
      from control subjects. CONCLUSIONS: We conclude that higher serum pth, but not
      lower serum vitamin D or calcium, is associated with oscc.

PMID- 26300677
TI  - Revealing a cancer diagnosis to patients: attitudes of patients, families,
      friends, nurses, and physicians in Lebanon-results of a cross-sectional study.
AB  - BACKGROUND: Disclosure of a cancer diagnosis to patients is a major problem for
      physicians in Lebanon. Our survey aimed to identify the attitudes of patients,
      families and friends, nurses, and physicians regarding disclosure of a cancer
      diagnosis. METHODS: Study participants included 343 physicians, nurses, cancer
      patients, families, and friends from clinics in two major hospitals in Lebanon.
      All completed a 29-item questionnaire that assessed, by demographic group, the
      information provided about cancer, opinions about the disclosure of the diagnosis
      to cancer patients, perceived consequences to patients, and the roles of family,
      friends, and religion. RESULTS: Overall, 7.8% of the patients were convinced that
      cancer is incurable. Nearly 82% preferred to be informed about their diagnosis.
      Similarly, 83% of physicians were in favour of disclosing a cancer diagnosis to
      their patients. However, only 14% of the physicians said that they revealed the
      truth to the patients themselves, with only 9% doing so immediately after
      confirmation of the diagnosis. Disclosure of a cancer diagnosis was preferred
      before the start of the treatment by 59% of the patients and immediately after
      confirmation of the diagnosis by 72% of the physicians. Overall, 86% of
      physicians, 51% of nurses, and 69% of patients and their families believed that
      religion helped with the acceptance of a cancer diagnosis. A role for family in
      accepting the diagnosis was reported by 74% of the patients, 56% of the nurses,
      and 88% of the physicians. All participants considered that fear was the most
      difficult feeling (63%) experienced by cancer patients, followed by pain (29%),
      pity (8%), and death (1%), with no statistically significant difference between
      the answers given by the participant groups. CONCLUSIONS: The social background
      in Lebanese society is the main obstacle to revealing the truth to cancer
      patients. Lebanese patients seem to prefer direct communication of the truth, but
      families take the opposite approach. Physicians also prefer to communicate the
      reality of the disease at the time of diagnosis, but in actuality, they instead
      disclose it progressively during treatment. Faith is helpful for acceptance of
      the diagnosis, and families play a key role in the support of the patients. An
      open discussion involving all members of society is necessary to attain a better
      understanding of this issue and to promote timely disclosure of a cancer
      diagnosis.

PMID- 26300678
TI  - Nonsurgical treatment of recurrent glioblastoma.
AB  - Standard treatment for glioblastoma multiforme is surgery followed by
      radiotherapy and chemotherapy, generally with temozolomide. However, disease
      recurs in almost all patients. Diagnosis of progression is complex given the
      possibility of pseudoprogression. The Response Assessment in Neuro-Oncology
      criteria increase the sensitivity for detecting progression. Most patients will
      not be candidates for new surgery or re-irradiation, and anticancer drugs are the
      most common approach for second-line treatment, if the patient's condition
      allows. Antiangiogenics, inhibitors of the epidermal growth factor receptor,
      nitrosoureas, and re-treatment with temozolomide have been studied in the second
      line, but a standard therapy has not yet been established. This review considers
      currently available medical treatment options for patients with glioblastoma
      recurrence. 

PMID- 26300679
TI  - The optimal organization of gynecologic oncology services: a systematic review.
AB  - BACKGROUND: A system-level organizational guideline for gynecologic oncology was
      identified by a provincial cancer agency as a key priority based on input from
      stakeholders, data showing more limited availability of multidisciplinary or
      specialist care in lower-volume than in higher-volume hospitals in the relevant
      jurisdiction, and variable rates of staging for ovarian and endometrial cancer
      patients. METHODS: A systematic review assessed the relationship of the
      organization of gynecologic oncology services with patient survival and surgical
      outcomes. The electronic databases medline and embase (ovid: 1996 through 9
      January 2015) were searched using terms related to gynecologic malignancies
      combined with organization of services, patterns of care, and various facility
      and physician characteristics. Outcomes of interest included overall or disease
      specific survival, short-term survival, adequate staging, and degree of
      cytoreduction or optimal cytoreduction (or both) for ovarian cancer patients by
      hospital or physician type, and rate of discrepancy in initial diagnoses and
      intraoperative consultation between non-specialist pathologists and gyne-oncology
      specialist pathologists. RESULTS: One systematic review and sixteen additional
      primary studies met the inclusion criteria. The evidence base as a whole was
      judged to be of lower quality; however, a trend toward improved outcomes with
      centralization of gynecologic oncology was found, particularly with respect to
      the gynecologic oncology care of patients with advanced-stage ovarian cancer.
      CONCLUSIONS: Improvements in outcomes with centralization of gynecologic oncology
      services can be attributed to a number of factors, including access to specialist
      care and multidisciplinary team management. Findings of this systematic review
      should be used with caution because of the limitations of the evidence base;
      however, an expert consensus process made it possible to create recommendations
      for implementation.

PMID- 26300682
TI  - Unusual presentation of metastatic sebaceous carcinoma and its response to
      chemotherapy: is genotyping a right answer for guiding chemotherapy in rare
      tumours?
AB  - Sebaceous carcinoma is a rare malignant tumour of skin. It commonly occurs in the
      head and neck region. The standard of care for localized disease is wide local
      excision followed by radiotherapy. Occasionally, sebaceous carcinoma can be
      associated with Muir-Torre syndrome, which is characterized by sebaceous lesions
      and carcinomas in the visceral organs. Metastatic sebaceous carcinoma is even
      rarer, with very little evidence about the role of chemotherapy in the treatment
      of metastatic disease. Here, we report a case of recurrent sebaceous carcinoma
      metastatic to the rectum (initially mimicking rectal cancer and Muir-Torre
      syndrome) in which the disease responded to multiple lines of chemotherapy. We
      also review the available literature on chemotherapy in this disease and discuss
      the role of tumour profiling and genotype-guided selection of chemotherapeutics
      in such rare tumours. 

PMID- 26300681
TI  - Eastern Canadian Gastrointestinal Cancer Consensus Conference 2014.
AB  - The annual Eastern Canadian Colorectal Cancer Consensus Conference was held in
      Montreal, Quebec, 23-25 October 2014. Expert radiation, medical, and surgical
      oncologists and pathologists involved in the management of patients with
      gastrointestinal malignancies participated in presentations and discussions
      resulting in consensus statements on such hot topics as management of
      neuroendocrine tumours, advanced and metastatic pancreatic cancer, and metastatic
      colorectal cancer. 

PMID- 26300684
TI  - The chronic condition of life.

PMID- 26300683
TI  - Increased treatment-related toxicity subsequent to an anti-PD-1 agent.

PMID- 26300680
TI  - Fertility preservation in reproductive-age women facing gonadotoxic treatments.
AB  - BACKGROUND: Advancements in the treatments for cancer and autoimmune and other
      hematologic conditions continue to improve survival and cure rates. Despite those
      changes, various gonadotoxic agents and other treatments can still compromise the
      future fertility of many women. Progress in medical and surgical reproductive
      technologies has helped to offset the reproductive consequences of the use of
      gonadotoxic therapies, and allows for future fertility and normal pregnancy.
      METHODS: A review of the literature was performed to outline the pathophysiology
      of gonadotoxicity from various treatments. The success of fertility preservation,
      fertility sparing, and cryopreservation options are reviewed. Barriers and
      facilitators to referral and oncofertility treatment in Canada are also outlined.
      RESULTS: According to the quality of the evidence, recommendations are made for
      fertility assessment, patient referral, cryopreservation, and other assisted
      reproductive technologies. CONCLUSIONS: To ensure ongoing fertility in women
      undergoing gonadotoxic treatments, assisted reproductive technologies can be
      combined with a multidisciplinary approach to patient assessment and referral.

PMID- 26300685
TI  - [Formula: see text]-Approximation for Graphic TSP.
AB  - The Travelling Salesman Problem is one of the fundamental and intensively studied
      problems in approximation algorithms. For more than 30 years, the best algorithm
      known for general metrics has been Christofides's algorithm with an approximation
      factor of [Formula: see text], even though the so-called Held-Karp LP relaxation
      of the problem is conjectured to have the integrality gap of only [Formula: see
      text]. Very recently, significant progress has been made for the important
      special case of graphic metrics, first by Oveis Gharan et al. (FOCS, 550-559,
      2011), and then by Momke and Svensson (FOCS, 560-569, 2011). In this paper, we
      provide an improved analysis of the approach presented in Momke and Svensson
      (FOCS, 560-569, 2011) yielding a bound of [Formula: see text] on the
      approximation factor, as well as a bound of [Formula: see text] for any epsilon>0
      for a more general Travelling Salesman Path Problem in graphic metrics.

PMID- 26300686
TI  - Sitting Closer to Friends than Enemies, Revisited.
AB  - Signed graphs, i.e., undirected graphs with edges labelled with a plus or minus
      sign, are commonly used to model relationships in social networks. Recently,
      Kermarrec and Thraves (2011) initiated the study of the problem of appropriately
      visualising the network: They asked whether any signed graph can be embedded into
      the metric space [Formula: see text] in such a manner that every vertex is closer
      to all its friends (neighbours via positive edges) than to all its enemies
      (neighbours via negative edges). Interestingly, embeddability into [Formula: see
      text] can be expressed as a purely combinatorial problem. In this paper we pursue
      a deeper study of this case, answering several questions posed by Kermarrec and
      Thraves. First, we refine the approach of Kermarrec and Thraves for the case of
      complete signed graphs by showing that the problem is closely related to the
      recognition of proper interval graphs. Second, we prove that the general case,
      whose polynomial-time tractability remained open, is in fact NP-complete.
      Finally, we provide lower and upper bounds for the time complexity of the general
      case: we prove that the existence of a subexponential time (in the number of
      vertices and edges of the input signed graph) algorithm would violate the
      Exponential Time Hypothesis, whereas a simple dynamic programming approach gives
      a running time single-exponential in the number of vertices.

PMID- 26300687
TI  - On the Question of Site-Selective Ligand Exchange in Carboxylate-Substituted
      Metal Oxo Clusters.
AB  - Reaction of [Ti4Zr4O6(OBu)4(OMc)16] (OMc = methacrylate) with acetylacetone
      (acacH) resulted in dissection of the cluster and formation of [Ti(OBu)2(acac)2]
      and the smaller cluster [Ti2Zr4O4(OMc)16]. In contrast, the same reaction with
      [Zr6O4(OH)4(OOCR)12]2.6RCOOH (R = Et, CH2CH=CH2) led to site-selective
      substitution of two carboxylate ligands and formation of isostructural
      [Zr6O4(OH)4(OOCR)12-x (acac) x ]2.6RCOOH (x <= 1).

PMID- 26300689
TI  - Possible explanation of excess events in the search for jets, missing transverse
      momentum and a Z boson in pp collisions.
AB  - We study to which extent SUSY extensions of the Standard Model can describe the
      excess of events of 3.0 standard deviations observed by ATLAS in the on-Z signal
      region, respecting constraints by CMS on similar signal channels as well as
      constraints from searches for jets and [Formula: see text]. GMSB-like scenarios
      are typically in conflict with these constraints, and do not reproduce well the
      shape of the [Formula: see text] distribution of the data. An alternative
      scenario with two massive neutralinos can improve fits to the total number of
      events as well as to the [Formula: see text] and [Formula: see text]
      distributions. Such a scenario can be realised within the NMSSM.

PMID- 26300690
TI  - An unbiased Hessian representation for Monte Carlo PDFs.
AB  - We develop a methodology for the construction of a Hessian representation of
      Monte Carlo sets of parton distributions, based on the use of a subset of the
      Monte Carlo PDF replicas as an unbiased linear basis, and of a genetic algorithm
      for the determination of the optimal basis. We validate the methodology by first
      showing that it faithfully reproduces a native Monte Carlo PDF set (NNPDF3.0),
      and then, that if applied to Hessian PDF set (MMHT14) which was transformed into
      a Monte Carlo set, it gives back the starting PDFs with minimal information loss.
      We then show that, when applied to a large Monte Carlo PDF set obtained as
      combination of several underlying sets, the methodology leads to a Hessian
      representation in terms of a rather smaller set of parameters (MC-H PDFs),
      thereby providing an alternative implementation of the recently suggested Meta
      PDF idea and a Hessian version of the recently suggested PDF compression
      algorithm (CMC-PDFs). The mc2hessian conversion code is made publicly available
      together with (through LHAPDF6) a Hessian representations of the NNPDF3.0 set,
      and the MC-H PDF set.

PMID- 26300692
TI  - Pieces of the flavour puzzle.
AB  - An overview of the flavour problem is presented, with emphasis on the theoretical
      efforts to find a satisfactory description of the fermion masses and the mixing
      angles.

PMID- 26300693
TI  - 'I learned to be okay with talking about sex and safety': assessing the efficacy
      of a theatre-based HIV prevention approach for adolescents in North Carolina.
AB  - Adolescents are at increased risk of HIV and sexually transmitted infections
      (STIs) in the Southern states of the USA, where rates among youth are higher than
      in the rest of the nation. This paper reports on findings from a pilot study of
      an HIV prevention intervention that uses interactive theatre to educate young
      people about sexual health. The intervention was developed in Los Angeles and
      adapted for testing in the South of the USA, with its legacy of abstinence-based
      approaches to sexual health education. This study assessed intervention effects
      among a sample of young people in two public high schools in North Carolina. We
      used a pre-test, post-test quasi-experimental evaluation design to assess changes
      in 317 ninth grade participants' knowledge and attitudes about HIV. At post-test,
      we found statistically significant increases in participants' HIV knowledge (t=
      60.14; p=.001), as well as changes in attitudes (X2 =8.23; p=.042) and awareness
      (X2 =4.94; p=.026). Focus group data corroborated increase in HIV knowledge and
      reduction in HIV stigma as successful outcomes of intervention participation. The
      findings make an important contribution to the literature on theatre-based
      interventions for sexual health education. Furthermore, they highlight the
      importance of considering socio-cultural and political context in implementing
      HIV prevention interventions in schools.

PMID- 26300694
TI  - Professional practice models for nurses in low-income countries: an integrative
      review.
AB  - BACKGROUND: Attention is turning to nurses, who form the greatest proportion of
      health personnel worldwide, to play a greater role in delivering health services
      amidst a severe human resources for health crisis and overwhelming disease burden
      in low-income countries. Nurse leaders in low-income countries must consider
      essential context for nurses to fulfill their professional obligation to deliver
      safe and reliable health services. Professional practice models (PPMs) have been
      proposed as a framework for strategically positioning nurses to impact health
      outcomes. PPMs comprise 5 elements: professional values, patient care delivery
      systems, professional relationships, management approach and remuneration. In
      this paper, we synthesize the existing literature on PPMs for nurses in low
      income countries. METHODS: An integrative review of CINAHL-EBSCO, PubMed and
      Scopus databases for English language journal articles published after 1990.
      Search terms included nurses, professionalism, professional practice models, low
      income countries, developing countries and relevant Medical Subject Heading Terms
      (MeSH). RESULTS: Sixty nine articles published between 1993 and 2014 were
      included in the review. Twenty seven articles examined patient care delivery
      models, 17 professional relationships, 12 professional values, 11 remuneration
      and 1 management approach. One article looked at comprehensive PPMs. CONCLUSIONS:
      Adopting comprehensive PPMs or their components can be a strategy to exploit the
      capacity of nurses and provide a framework for determining the full expression of
      the nursing role.

PMID- 26300695
TI  - A case-based approach to implementing guidelines for stroke prevention in
      patients with atrial fibrillation: balancing the risks and benefits.
AB  - Atrial fibrillation (AF) puts patients at risk of complications, including
      stroke. Warfarin therapy has been the mainstay of antithrombotic treatment for
      reducing the risk of stroke in AF. However, warfarin has limitations that have
      motivated development of several novel oral anticoagulants (NOACs), including
      dabigatran, rivaroxaban, apixaban, and edoxaban. Clinical trials demonstrate that
      the NOACs offer efficacy and safety that are equivalent to, or better than, those
      of warfarin for reducing the risk of stroke in patients with nonvalvular AF. This
      review examines stroke risk reduction in patients with AF from the perspective of
      the clinician balancing the risks and benefits of treatment options, evaluates
      the most recent guidelines, and discusses 2 hypothetical patient cases to better
      illustrate how clinicians may apply available data in the clinical setting. We
      reviewed guidelines for the reduction of stroke risk in AF and data from clinical
      trials on the NOACs. Choosing antithrombotic treatment involves assessing the
      benefits of therapy versus its risks. Risk indexes, including CHADS2, CHA2DS2
      VASc, and HAS-BLED can help determine how to treat patients with AF. Current
      guidelines suggest using these risk indexes to customize treatment to individual
      patients. Many current treatment guidelines also incorporate recommendations for
      the use of NOACs as an alternative to warfarin. As additional data emerge and
      guidelines are updated, these recommendations will likely evolve. In the interim,
      clinicians may consider published guidelines and clinical trial results on NOACs.
      Real-world experience will provide clinicians with additional insight into their
      treatment decisions. 

PMID- 26300696
TI  - Cost-effectiveness analysis of routine immunization and supplementary
      immunization activity for measles in a health district of Benin.
AB  - BACKGROUND: This study was carried out at district level to describe the cost
      structure and measure the effectiveness of delivering supplementary immunization
      activity (SIA) and routine immunization (RI) for measles in Benin, a country
      heavily affected by this disease. METHODS: This cost-effectiveness study was
      cross sectional and considered 1-year time horizon. RI consists to vaccinate an
      annual cohort of children aged 0-1 year old and SIA consists to provide a second
      dose of measles vaccine to children aged 0-5 years old in order to reach both
      those who did not seroconvert and who were not vaccinated through RI. Ingredients
      approach to costing was used. Effectiveness indicators included measles vaccine
      doses used, vaccinated children, measles cases averted and disability adjusted
      life years averted. Data were collected from all the 18 health care centers of
      the health district of Natitingou for the year 2011. In the analysis, the
      coverage was 89 % for RI and 104 % for SIA. RESULTS: SIA total cost was higher
      than RI total cost (15,796,560 FCFA versus 9,851,938 FCFA). Personnel and
      vaccines were the most important cost components for the two strategies. Fuel for
      cold chain took a non-negligible part of RI total cost (4.03 %) because 83 % of
      refrigerators were working with kerosene. Cost structures were disproportionate
      as social mobilization and trainings were not financed during RI contrarily to
      SIA. In comparison with no intervention, the two strategies combined permitted to
      avoid 12,671 measles cases or 19,023 DALYs. The benefit of SIA was 5601 measles
      cases averted and 6955 additional DALYs averted. Cost per vaccinated child for
      SIA (442 FCFA) was lower than for RI (1242 FCFA), in line with previous data from
      the literature. Cost per DALY averted was 2271 FCFA (4.73 USD) for SIA and 769
      FCFA (1.60 USD) for RI. Analysis showed that low vaccine efficacy decreased the
      cost-effectiveness ratios for the two strategies. SIA was more cost-effective
      when the proportion of previously unvaccinated children was higher. For the two
      strategies, costs per DALY were more likely to vary with measles case fatality
      ratio. CONCLUSIONS: SIA is costlier than RI. Both SIA and RI for measles are cost
      effective interventions to improve health in Benin compared to no vaccination.
      Policy makers could make RI more efficient if sufficient funds were allocated to
      communications activities and to staff motivation (trainings, salaries).

PMID- 26300691
TI  - Physics at the [Formula: see text] linear collider.
AB  - A comprehensive review of physics at an [Formula: see text] linear collider in
      the energy range of [Formula: see text] GeV-3 TeV is presented in view of recent
      and expected LHC results, experiments from low-energy as well as astroparticle
      physics. The report focusses in particular on Higgs-boson, top-quark and
      electroweak precision physics, but also discusses several models of beyond the
      standard model physics such as supersymmetry, little Higgs models and extra gauge
      bosons. The connection to cosmology has been analysed as well.

PMID- 26300697
TI  - High rates of homicide in a rural South African population (2000-2008): findings
      from a population-based cohort study.
AB  - BACKGROUND: South Africa has continued to receive increasing attention due to
      unprecedented high levels of violence. Homicide-related violence accounts for a
      significant proportion of unnatural deaths and contributes significantly to loss
      of years of expected life. We investigated levels and factors associated with
      homicide-related deaths and identify communities with excessively high homicide
      risk in a typical rural South African population. METHOD: Data drawn from verbal
      autopsies conducted on all deaths recorded during annual demographic and health
      surveillance in KwaZulu Natal, South Africa were used to derive the cumulative
      probability of death from homicide over a nine-year period (2000-2008). Weibull
      regression methods were used to investigate factors associated with homicide
      deaths. A Kulldorff spatial scan statistic was used to identify spatial clusters
      of homicide-related deaths. RESULTS: With 536 homicide-related deaths, and a
      median seven years of follow-up, the study found an overall homicide incidence
      rate of 66 deaths per 100, 000 person-years of observation (PYOs) (95 % CI 60-72)
      for the period under study. Death related to the use of firearms was the leading
      reported method of homicide (65 %) and most deaths occurred over weekends (43 %).
      Homicides are the second-most common cause of death in men aged 25-34 after HIV
      related deaths (including TB) in this community, at 210 deaths per 100,000 PYOs,
      and was highest among 55-64 year old women, at 78 deaths per 100,000 PYOs.
      Residency status, age, socioeconomic status, and highest education level attained
      independently predicted the risk of homicide death. The spatial distribution of
      homicide deaths was not homogenous and the study identified two clear
      geographical clusters with significantly elevated homicide risk. CONCLUSION: The
      high rates of homicide observed in this typical rural South African population -
      particularly among men - underscore the need for urgent interventions to reduce
      this tragic and theoretically preventable loss of life in this population and
      similar South African settings.

PMID- 26300698
TI  - Efficient prediction designs for random fields.
AB  - For estimation and predictions of random fields, it is increasingly acknowledged
      that the kriging variance may be a poor representative of true uncertainty.
      Experimental designs based on more elaborate criteria that are appropriate for
      empirical kriging (EK) are then often non-space-filling and very costly to
      determine. In this paper, we investigate the possibility of using a compound
      criterion inspired by an equivalence theorem type relation to build designs quasi
      optimal for the EK variance when space-filling designs become unsuitable. Two
      algorithms are proposed, one relying on stochastic optimization to explicitly
      identify the Pareto front, whereas the second uses the surrogate criteria as
      local heuristic to choose the points at which the (costly) true EK variance is
      effectively computed. We illustrate the performance of the algorithms presented
      on both a simple simulated example and a real oceanographic dataset. (c) 2014 The
      Authors. Applied Stochastic Models in Business and Industry published by John
      Wiley & Sons, Ltd.

PMID- 26300699
TI  - Paleomagnetic recording fidelity of nonideal magnetic systems.
AB  - : A suite of near-identical magnetite nanodot samples produced by electron-beam
      lithography have been used to test the thermomagnetic recording fidelity of
      particles in the 74-333 nm size range; the grain size range most commonly found
      in rocks. In addition to controlled grain size, the samples had identical
      particle spacings, meaning that intergrain magnetostatic interactions could be
      controlled. Their magnetic hysteresis parameters were indicative of particles
      thought not to be ideal magnetic recorders; however, the samples were found to be
      excellent thermomagnetic recorders of the magnetic field direction. They were
      also found to be relatively good recorders of the field intensity in a standard
      paleointensity experiment. The samples' intensities were all within ~15% of the
      expected answer and the mean of the samples within 3% of the actual field. These
      nonideal magnetic systems have been shown to be reliable records of the
      geomagnetic field in terms of both direction and intensity even though their
      magnetic hysteresis characteristics indicate less than ideal magnetic grains. KEY
      POINTS: Nonideal magnetic systems accurately record field directionWeak-field
      remanences more stable than strong-field remanences.

PMID- 26300700
TI  - Intolerance of Uncertainty: Shaping an Agenda for Research on Coping with
      Multiple Sclerosis.
AB  - Multiple sclerosis (MS) is a chronic and progressive neurologic condition that,
      by its nature, carries uncertainty as a hallmark characteristic. Although all
      patients face uncertainty, there is variability in how individuals cope with its
      presence. In other populations, the concept of "intolerance of uncertainty" has
      been conceptualized to explain this variability such that individuals who have
      difficulty tolerating the possibility of future occurrences may engage in
      thoughts or behaviors by which they attempt to exert control over that
      possibility or lessen the uncertainty but may, as a result, experience worse
      outcomes, particularly in terms of psychological well-being. This topical review
      introduces MS-focused researchers, clinicians, and patients to intolerance of
      uncertainty, integrates the concept with what is already understood about coping
      with MS, and suggests future steps for conceptual, assessment, and treatment
      focused research that may benefit from integrating intolerance of uncertainty as
      a central feature. 

PMID- 26300701
TI  - Impact of Proactive Case Management by Multiple Sclerosis Specialist Nurses on
      Use of Unscheduled Care and Emergency Presentation in Multiple Sclerosis: A Case
      Study.
AB  - BACKGROUND: Multiple sclerosis (MS) affects approximately 100,000 people in the
      United Kingdom, with rising emergency admissions to the hospital. The multiple
      sclerosis specialist nurse plays a pivotal role in managing MS care in the United
      Kingdom, and there is anecdotal evidence that this role can help avoid emergency
      presentations and unnecessary hospital admissions. METHODS: A retrospective
      service evaluation took place in one established MS nursing service. The impact
      of the introduction of proactive nurse-led management and a rapid response
      service on rates of emergency presentation, hospital admission, and bed use was
      examined. The primary intervention was the introduction of extra nursing hours (6
      hours per week) and the reallocation of some routine administrative duties, which
      allowed the service to move to a proactive management model aimed at avoiding the
      need for unplanned care. In addition, a care pathway was implemented in the
      emergency department for patients with MS who did present. RESULTS: Reduction in
      utilization was from a mean of 2700 bed-days per year (2002-2006) to a mean of
      198 bed-days per year (2007-2013). CONCLUSIONS: During a 10-year period, moving
      from reactive management to proactive management demonstrated an increase in
      complex specialist nursing interventions and led to a decrease in emergency
      presentation and bed use at the local acute-care center.

PMID- 26300702
TI  - Fear of Falling Is Associated with Recurrent Falls in People with Multiple
      Sclerosis: A Longitudinal Cohort Study.
AB  - BACKGROUND: People with multiple sclerosis (MS) fall frequently, and there are
      few clinically valid tools to measure the risk factors for falls. We assessed the
      unidimensionality of the 7-item Falls Efficacy Scale-International (FES-I), a
      measure of fear of falling, and determined whether the 7-item FES-I is associated
      with recurrent falls in people with MS. METHODS: Falls were counted prospectively
      for 6 months using fall calendars in 58 people with MS (age, 18-50 years;
      Expanded Disability Status Scale score, 0-6). The FES-I was administered at
      baseline, and its unidimensionality was assessed by confirmatory factor analysis.
      The relationship between FES-I score and future falls, after adjusting for
      recurrent falls in the past year, was assessed by logistic regression. RESULTS:
      Fifty-four participants who completed all assessments were included in the
      analysis. Goodness-of-fit indices confirmed a single-factor solution for the 7
      item FES-I (discrepancy chi(2), P = .101; Tucker-Lewis index, 0.953; comparative
      fit index, 0.969; root mean square error of approximation, 0.098). There was a
      significant association between fear of falling and falls in the following 3
      months, independent of recurrent falls in the past year (odds ratio = 1.22, 95%
      confidence interval, 1.04-1.43, P = .016). CONCLUSIONS: The 7-item FES-I
      demonstrates good construct validity, allowing the total score to be used as a
      measure of fear of falling in people with MS. Fear of falling, as measured by the
      7-item FES-I, is associated with future recurrent falls independent of past
      recurrent falls in people with MS.

PMID- 26300703
TI  - Do Physical Therapy Interventions Affect Urinary Incontinence and Quality of Life
      in People with Multiple Sclerosis?: An Evidence-Based Review.
AB  - BACKGROUND: Multiple sclerosis (MS) presents with many debilitating symptoms,
      including urinary incontinence (UI), that physical therapy (PT) may address; UI
      is widely prevalent, but PT management of symptoms lacks consensus. A meta
      analysis of long-term nonsurgical and nonpharmaceutical treatment options may
      supply this deficiency. We analyzed the current evidence for effectiveness of PT
      to decrease UI and improve quality of life (QOL) in people with MS. METHODS: An
      electronic search conducted through November 26, 2013, included the following
      search terms: incontinence, bladder dysfunction, urinary incontinence, multiple
      sclerosis, MS, physical therapy, physiotherapy, therapy, and rehabilitation.
      Criteria for inclusion were as follows: MS diagnosis, intervention involved PT
      for UI or bladder dysfunction, outcomes assessed QOL or UI, and at least a 4 of
      10 on the Physiotherapy Evidence Database scale or a 2b level of evidence.
      Outcomes were combined across studies, and effect sizes are depicted in forest
      plots. RESULTS: Six studies met the inclusion criteria. Between-group analysis
      revealed statistically significant differences in incontinence episodes and QOL,
      but did not reach significance for functional control mechanisms (eg,
      electromyography data on strength of contraction, relaxation, and endurance).
      Incontinence leakage episodes and QOL participation improved within groups.
      CONCLUSIONS: Meta-analysis indicates support for PT for minimizing incontinence
      compared with pretreatment and affecting incontinence and QOL more than control
      in people with MS. Protocols were heterogeneous regarding duration and type of PT
      intervention and were applied in different types of MS. Further research may
      reveal the most effective combination and variety of PT interventions for people
      with MS.

PMID- 26300705
TI  - Prevention and Management of Infusion-Associated Reactions in the Comparison of
      Alemtuzumab and Rebif((r)) Efficacy in Multiple Sclerosis (CARE-MS) Program.
AB  - BACKGROUND: Alemtuzumab is a humanized monoclonal antibody approved in several
      countries for treatment of relapsing-remitting multiple sclerosis (RRMS). This
      report summarizes the experience with infusion-associated reactions (IARs) in two
      phase 3 trials of alemtuzumab in RRMS and examines skilled nursing interventions
      in IAR prevention and management. METHODS: In the Comparison of Alemtuzumab and
      Rebif((r)) Efficacy in Multiple Sclerosis (CARE-MS) studies, patients with RRMS
      (treatment naive [CARE-MS I] or with inadequate response [defined as at least one
      relapse] to previous therapy [CARE-MS II]) received intravenous infusions of
      alemtuzumab 12 mg/day on 5 consecutive days at baseline and on 3 consecutive days
      12 months later. Patients were monitored for IARs during and after each infusion.
      An IAR was defined as any adverse event occurring during any infusion or within
      24 hours after infusion. RESULTS: The IARs affected 90.1% of patients receiving
      alemtuzumab. The most common IARs were headache, rash, pyrexia, nausea, and
      flushing; most were mild to moderate in severity. Management of IARs consisted of
      infusion interruption or rate reduction, pharmacologic therapies, and continual
      patient education and support. Medication administration before and during
      alemtuzumab infusion reduced IAR severity. Forty-five of 972 alemtuzumab-treated
      patients (4.6%) required interruption of the first treatment course (ie,
      infusions did not occur on consecutive days); of these, 24 (53.3%) were still
      able to complete the first and second full treatment courses. CONCLUSIONS: Nurses
      played an invaluable role in the detection and management of IARs in the CARE-MS
      studies. Best practices for management of IARs associated with alemtuzumab
      include patient and caregiver education, medication to lessen IAR severity,
      infusion monitoring, and discharge planning.

PMID- 26300704
TI  - Selecting Rehabilitation Outcome Measures for People with Multiple Sclerosis.
AB  - Despite the well-known benefits of using standardized outcome measures (OMs) in
      clinical practice, a variety of barriers interfere with their use. In particular,
      rehabilitation therapists lack sufficient knowledge in selecting appropriate OMs.
      The challenge is compounded when working with people with multiple sclerosis (MS)
      owing to heterogeneity of the patient population and symptom variability in
      individual patients. To help overcome these barriers, the American Physical
      Therapy Association appointed the Multiple Sclerosis Outcome Measures Task Force
      to review and make evidence-based recommendations for OM use in clinical
      practice, education, and research specific to people with MS. Sixty-three OMs
      were reviewed based on their clinical utility, psychometric properties, and a
      consensus evaluation of the appropriateness of use for people with MS. We sought
      to illustrate use of the recommendations for two cases. The first case involves a
      43-year-old man with new-onset problems after an exacerbation. The second case
      pertains to an outpatient clinic interested in assessing the effectiveness of
      their MS rehabilitation program. For each case, clinicians identified areas that
      were important to assess and various factors deemed important for OM selection.
      Criteria were established and used to assist in OM selection. In both cases, the
      described processes narrowed the selection of OMs and assisted with choosing the
      most appropriate ones. The recommendations, in addition to the processes
      described in these two cases, can be used by clinicians in any setting working
      with patients with MS across the disability spectrum. 

PMID- 26300706
TI  - Access to Preventive Health Care in Severely Disabled Women with Multiple
      Sclerosis.
AB  - BACKGROUND: Nonambulatory patients may be at risk for poor access to preventive
      health screening. Few studies have reported on this access in severely disabled
      women with multiple sclerosis (MS). We sought to describe preventive medical care
      in the most disabled women with MS and to identify factors that may influence
      access to care. METHODS: Patient records from the Partners MS Center database
      were reviewed. Women with Expanded Disability Status Scale scores of 7 or greater
      were selected. Proportions of patients with preventive-care visits were compared
      with 2012 Centers for Disease Control and Prevention (CDC) guidelines and
      normative data. Logistic regression was used to assess demographic and disease
      effects on receiving services. RESULTS: Forty-eight percent of patients had
      annual mammograms versus 72% of healthy women and the CDC target of 81%; 41.8%
      had Papanicolaou smears within 3 years compared with 82% of healthy women and the
      target of 93%; and 61.2% aged 50 years and older ever had a colonoscopy compared
      with the target of 70%. Younger age predicted lower rates of colonoscopy (P <
      .002) and mammography (P < .004), and shorter disease duration predicted lower
      rates of mammography (P < .004). Obesity was associated with a lower likelihood
      of colonoscopy (P = .007) and bone density screening (P = .02). CONCLUSIONS:
      Women with severe MS disability are vulnerable to significantly decreased access
      to preventive care. The influence of patient and physician factors and the
      possible consequent delays in cancer diagnosis should be further clarified.

PMID- 26300707
TI  - Editorial.

PMID- 26300708
TI  - Gaussian Accelerated Molecular Dynamics: Unconstrained Enhanced Sampling and Free
      Energy Calculation.
AB  - A Gaussian accelerated molecular dynamics (GaMD) approach for simultaneous
      enhanced sampling and free energy calculation of biomolecules is presented. By
      constructing a boost potential that follows Gaussian distribution, accurate
      reweighting of the GaMD simulations is achieved using cumulant expansion to the
      second order. Here, GaMD is demonstrated on three biomolecular model systems:
      alanine dipeptide, chignolin folding, and ligand binding to the T4-lysozyme.
      Without the need to set predefined reaction coordinates, GaMD enables
      unconstrained enhanced sampling of these biomolecules. Furthermore, the free
      energy profiles obtained from reweighting of the GaMD simulations allow us to
      identify distinct low-energy states of the biomolecules and characterize the
      protein-folding and ligand-binding pathways quantitatively.

PMID- 26300709
TI  - Constant-pH Hybrid Nonequilibrium Molecular Dynamics-Monte Carlo Simulation
      Method.
AB  - A computational method is developed to carry out explicit solvent simulations of
      complex molecular systems under conditions of constant pH. In constant-pH
      simulations, preidentified ionizable sites are allowed to spontaneously protonate
      and deprotonate as a function of time in response to the environment and the
      imposed pH. The method, based on a hybrid scheme originally proposed by H. A.
      Stern (J. Chem. Phys. 2007, 126, 164112), consists of carrying out short
      nonequilibrium molecular dynamics (neMD) switching trajectories to generate
      physically plausible configurations with changed protonation states that are
      subsequently accepted or rejected according to a Metropolis Monte Carlo (MC)
      criterion. To ensure microscopic detailed balance arising from such
      nonequilibrium switches, the atomic momenta are altered according to the
      symmetric two-ends momentum reversal prescription. To achieve higher efficiency,
      the original neMD-MC scheme is separated into two steps, reducing the need for
      generating a large number of unproductive and costly nonequilibrium trajectories.
      In the first step, the protonation state of a site is randomly attributed via a
      Metropolis MC process on the basis of an intrinsic pKa; an attempted
      nonequilibrium switch is generated only if this change in protonation state is
      accepted. This hybrid two-step inherent pKa neMD-MC simulation method is tested
      with single amino acids in solution (Asp, Glu, and His) and then applied to
      turkey ovomucoid third domain and hen egg-white lysozyme. Because of the simple
      linear increase in the computational cost relative to the number of titratable
      sites, the present method is naturally able to treat extremely large systems. 

PMID- 26300710
TI  - Null effect of ginsenoside Rb1 on improving glycemic status in men during a
      resistance training recovery.
AB  - BACKGROUND: Ginsenoside Rb1, a principle active ingredients of Panax ginseng, has
      been shown to lower blood glucose in animals and increase insulin secretion in
      cultured insulinoma cells. The aim of this study was to determine the effects of
      daily ginsenoside Rb1 supplementation on circulating glucose and insulin levels
      in men during a 5-day recovery period after an acute bout of resistance exercise.
      METHODS: Twelve gymnasts (20.5 +/- 0.3 years of age) participated in this double
      blind placebo-controlled crossover trial. They were challenged by a lower-limb
      resistance exercise at a weight load of 85 % one-repetition maximal (1-RM) for 10
      repetitions, six sets of the movement. Rb1 (1 ng/kg) or Placebo was orally
      delivered to participants daily during a 5-day recovery period after challenge.
      Circulating insulin, glucose and heart rate variability (HRV) were measured under
      fasted condition in the morning at Days 1, Day 3, and Day 5 during recovery.
      RESULTS: No significant effect of Rb1 on circulating glucose and insulin levels
      were found among participants during the 5-day recovery period. A persistent
      elevation in sympathetic nervous activity, indicated by increased HRV-low
      frequency/high frequency (HRV-LF/HF) power, during the Rb1 trial was observed.
      CONCLUSIONS: The result of the study suggests that the null effect of Rb1
      supplementation on lowering glucose and insulin levels of participants may be
      associated with chronic sympathetic activation.

PMID- 26300711
TI  - A hybrid method for inversion of 3D DC resistivity logging measurements.
AB  - This paper focuses on the application of hp hierarchic genetic strategy (hp-HGS)
      for solution of a challenging problem, the inversion of 3D direct current (DC)
      resistivity logging measurements. The problem under consideration has been
      formulated as the global optimization one, for which the objective function
      (misfit between computed and reference data) exhibits multiple minima. In this
      paper, we consider the extension of the hp-HGS strategy, namely we couple the hp
      HGS algorithm with a gradient based optimization method for a local search.
      Forward simulations are performed with a self-adaptive hp finite element method,
      hp-FEM. The computational cost of misfit evaluation by hp-FEM depends strongly on
      the assumed accuracy. This accuracy is adapted to the tree of populations
      generated by the hp-HGS algorithm, which makes the global phase significantly
      cheaper. Moreover, tree structure of demes as well as branch reduction and
      conditional sprouting mechanism reduces the number of expensive local searches up
      to the number of minima to be recognized. The common (direct and inverse)
      accuracy control, crucial for the hp-HGS efficiency, has been motivated by
      precise mathematical considerations. Numerical results demonstrate the
      suitability of the proposed method for the inversion of 3D DC resistivity logging
      measurements.

PMID- 26300712
TI  - Topology driven modeling: the IS metaphor.
AB  - In order to define a new method for analyzing the immune system within the realm
      of Big Data, we bear on the metaphor provided by an extension of Parisi's model,
      based on a mean field approach. The novelty is the multilinearity of the
      couplings in the configurational variables. This peculiarity allows us to compare
      the partition function [Formula: see text] with a particular functor of
      topological field theory-the generating function of the Betti numbers of the
      state manifold of the system-which contains the same global information of the
      system configurations and of the data set representing them. The comparison
      between the Betti numbers of the model and the real Betti numbers obtained from
      the topological analysis of phenomenological data, is expected to discover hidden
      n-ary relations among idiotypes and anti-idiotypes. The data topological analysis
      will select global features, reducible neither to a mere subgraph nor to a metric
      or vector space. How the immune system reacts, how it evolves, how it responds to
      stimuli is the result of an interaction that took place among many entities
      constrained in specific configurations which are relational. Within this
      metaphor, the proposed method turns out to be a global topological application of
      the S[B] paradigm for modeling complex systems.

PMID- 26300713
TI  - Logic circuits from zero forcing.
AB  - We design logic circuits based on the notion of zero forcing on graphs; each gate
      of the circuits is a gadget in which zero forcing is performed. We show that such
      circuits can evaluate every monotone Boolean function. By using two vertices to
      encode each logical bit, we obtain universal computation. We also highlight a
      phenomenon of "back forcing" as a property of each function. Such a phenomenon
      occurs in a circuit when the input of gates which have been already used at a
      given time step is further modified by a computation actually performed at a
      later stage. Finally, we show that zero forcing can be also used to implement
      reversible computation. The model introduced here provides a potentially new tool
      in the analysis of Boolean functions, with particular attention to monotonicity.
      Moreover, in the light of applications of zero forcing in quantum mechanics, the
      link with Boolean functions may suggest a new directions in quantum control
      theory and in the study of engineered quantum spin systems. It is an open
      technical problem to verify whether there is a link between zero forcing and
      computation with contact circuits.

PMID- 26300714
TI  - Identifying peer effects using spatial analysis: the role of peers on risky
      sexual behavior.
AB  - This paper explores the role of peer effects on early sexual debut for a sample
      of adolescents using data from the National Longitudinal Study on Adolescent
      Health (Add Health). Most studies analyzing peer influences ignore the
      "reflection" problem that occurs with studying peer effects. To address the
      reflection problem, this paper employs a spatial econometric approach to estimate
      a social interactions model. This is the first study in the literature on
      adolescent risky sexual behavior to use this approach to estimate peer effects.
      Similar to other research on peer effects and adolescent risky sexual behavior,
      this paper finds the existence of peer effects. However, the more vital outcome
      from this study is that older and male peers increase the likelihood of
      adolescent early sexual debut, while peers whose mothers are more open about
      sexual activity decrease adolescent risky sexual behavior. This methodology can
      help further our knowledge about the social context that influences adolescent
      sexual behavior.

PMID- 26300715
TI  - Systemic deterrence of aphid probing and feeding by novel beta-damascone
      analogues.
AB  - beta-Damascone appeared a weak attractant close to not active to Myzus persicae,
      but modifications of its structure caused the avoidance of treated leaves by
      aphids during settling and reluctance to probe in simple choice- and no-choice
      experiments in previous studies. Here, the electrical penetration graph (EPG)
      technique, which allows monitoring of aphid probing within plant tissues, was
      applied to explore the biological background and localisation in plant tissues of
      the deterrent activities of beta-damascone and its analogues. Activity of beta
      damascone and beta-damascone-derived compounds depended on their substituents,
      which was manifested in the variation in the potency of the behavioural effect
      and differences in aphid probing phases that were affected. beta-Damascone
      appeared a behaviourally inactive compound. The moderately active beta-damascone
      ester affected aphid activities only during the phloem phase. The highly active
      deterrents-dihydro-beta-damascol, beta-damascone acetate, delta-bromo-gamma
      lactone, and unsaturated gamma-lactone-affected pre-phloem and phloem aphid
      probing activities. The most effective structural modification that evoked the
      strongest negative response from M. persicae was the transformation of beta
      damascone into delta-bromo-gamma-lactone. The behavioural effect of this
      transformation was demonstrated in frequent interruption of probing in peripheral
      tissues, which caused repeated failures in finding sieve elements, and reduction
      in the ingestion time during the phloem phase in favour of watery salivation. The
      inhibition of aphid probing at both the pre-phloem and phloem levels reveals the
      passage of the compounds studied through the plant surface and their distribution
      within plant tissues in a systemic way, which may reduce the risk of the
      transmission of non-persistent and persistent viruses.

PMID- 26300716
TI  - The influence of estimated retail tobacco sale price increase on smokers' smoking
      habit in Jiangxi province, China: a cross-sectional study.
AB  - INTRODUCTION: China is the biggest tobacco producer and consumer in the world.
      Raising cigarette taxes and increasing tobacco retail prices have been prove as
      effective strategies to reduce tobacco consumption and the prevalence of smoking
      in western countries. But in China, it is uncertain how an increase of cigarette
      retail price will influence the tobacco consumption. METHODS: From April to July,
      2012, we selected 4025 residents over 15 years by a three stage random sampling
      in four cities, Jiangxi Province, China. We conducted interviews of their current
      smoking habits and how they would change their smoking behavior if tobacco retail
      prices increase. RESULTS: Overall, the prevalence of smoking is 27 % (47 % for
      male, 3.1 % for female). 15 % of smokers have tried to quit smoking in the past
      but all relapsed (168/1088), and over 50 % of current smokers do not want to
      quit, The average cigarette price per pack is 1.1 USD (range = 0.25-5.0). If
      retail cigarette prices increases by 50 %, 45 % of smokers say they will smoke
      fewer cigarettes, 20 % will change to cheaper brands and 5 % will attempt to quit
      smoking. Smokers who have intention to quit smoking are more sensitive to retail
      cigarette price increase. With retail cigarette price increases, more smokers
      will attempt to quit smoking. CONCLUSION: Chinese smokers will change their
      smoking habits if tobacco retail prices increase. Consequently the Chinese
      government should enact tobacco laws which increase the retail cigarette price.
      The implementation of new tobacco laws could result in lowering the prevalence of
      smoking. Meanwhile, price increase measures need to apply to all cigarette brands
      to avoid smokers switching cigarettes to cheaper brands.

PMID- 26300717
TI  - Electrochemical properties of titanium nitride nerve stimulation electrodes: an
      in vitro and in vivo study.
AB  - The in vivo electrochemical behavior of titanium nitride (TiN) nerve stimulation
      electrodes was compared to their in vitro behavior for a period of 90 days. Ten
      electrodes were implanted in two Gottingen minipigs. Four of these were used for
      electrical stimulation and electrochemical measurements. Five electrodes were
      kept in Ringer's solution at 37.5 degrees C, of which four were used for
      electrical stimulation and electrochemical measurements. The voltage transients
      measured in vivo were 13 times greater than in vitro at implantation and they
      continued to increase with time. The electrochemical properties in vivo and the
      tissue resistance (Rtissue) followed a similar trend with time. There was no
      consistent significant difference between the electrochemical properties of the
      in vivo and in vitro electrodes after the implanted period. The differences
      between the in vivo and in vitro electrodes during the implanted period show that
      the evaluation of electrochemical performance of implantable stimulation
      electrodes cannot be substituted with in vitro measurements. After the implanted
      period, however, the performance of the in vivo and in vitro electrodes in saline
      was similar. In addition, the changes observed over time during the post
      implantation period regarding the electrochemical properties of the in vivo
      electrodes and Rtissue were similar, which indicates that these changes are due
      to the foreign body response to implantation. 

PMID- 26300719
TI  - Variations of high frequency parameter of heart rate variability following
      osteopathic manipulative treatment in healthy subjects compared to control group
      and sham therapy: randomized controlled trial.
AB  - CONTEXT: Heart Rate Variability (HRV) indicates how heart rate changes in
      response to inner and external stimuli. HRV is linked to health status and it is
      an indirect marker of the autonomic nervous system (ANS) function. OBJECTIVE: To
      investigate the influence of osteopathic manipulative treatment (OMT) on cardiac
      autonomic modulation in healthy subjects, compared with sham therapy and control
      group. METHODS: Sixty-six healthy subjects, both male and female, were included
      in the present 3-armed randomized placebo controlled within subject cross-over
      single blinded study. Participants were asymptomatic adults (26.7 +/- 8.4 y, 51%
      male, BMI 18.5 +/- 4.8), both smokers and non-smokers and not on medications. At
      enrollment subjects were randomized in three groups: A, B, C. Standardized
      structural evaluation followed by a patient need-based osteopathic treatment was
      performed in the first session of group A and in the second session of group B.
      Standardized evaluation followed by a protocoled sham treatment was provided in
      the second session of group A and in the first session of group B. No
      intervention was performed in the two sessions of group C, acting as a time
      control. The trial was registered on clinicaltrials.gov identifier: NCT01908920.
      MAIN OUTCOMES MEASURES: HRV was calculated from electrocardiography before,
      during and after the intervention, for a total amount time of 25 min and
      considering frequency domain as well as linear and non-linear methods as outcome
      measures. RESULTS: OMT engendered a statistically significant increase of
      parasympathetic activity, as shown by High Frequency power (p < 0.001), expressed
      in normalized and absolute unit, and possibly decrease of sympathetic activity,
      as revealed by Low Frequency power (p < 0.01); results also showed a reduction of
      Low Frequency/High Frequency ratio (p < 0.001) and Detrended fluctuation scaling
      exponent (p < 0.05). CONCLUSIONS: Findings suggested that OMT can influence ANS
      activity increasing parasympathetic function and decreasing sympathetic activity,
      compared to sham therapy and control group.

PMID- 26300720
TI  - Neuroscientific and neuroanthropological perspectives in music therapy research
      and practice with patients with disorders of consciousness.
AB  - A growing understanding of music therapy with patients with disorders of
      consciousness (DOC) has developed from observing behavioral changes and using
      these to gain new ways of experiencing this research environment and setting.
      Neuroscience provides further insight into the effects of music therapy; however,
      various studies with similar protocols show different results. The
      neuroanthropological approach is informed by anthropological and philosophical
      frameworks. It puts emphasis on a research with and not just on human beings
      concerning the subject/object question within a research process. It examines
      relational aspects and outcomes in the context of working in an interdisciplinary
      team. This allows a broader view of music therapy in a reflective process and
      leads to a careful interpretation of behavioral reactions and imaging results.
      This article discusses the importance of the neuroanthropological perspective on
      our way of obtaining knowledge and its influence on therapeutic practice. It is
      important to consider how knowledge is generated as it influences the results.
      Data from two cases will be presented to illustrate the neuroanthropological
      approach by comparing quantitative PET data with qualitative results of video
      analyses. 

PMID- 26300718
TI  - Considerations for resting state functional MRI and functional connectivity
      studies in rodents.
AB  - Resting state functional MRI (rs-fMRI) and functional connectivity mapping have
      become widely used tools in the human neuroimaging community and their use is
      rapidly spreading into the realm of rodent research as well. One of the many
      attractive features of rs-fMRI is that it is readily translatable from humans to
      animals and back again. Changes in functional connectivity observed in human
      studies can be followed by more invasive animal experiments to determine the
      neurophysiological basis for the alterations, while exploratory work in animal
      models can identify possible biomarkers for further investigation in human
      studies. These types of interwoven human and animal experiments have a
      potentially large impact on neuroscience and clinical practice. However,
      impediments exist to the optimal application of rs-fMRI in small animals, some
      similar to those encountered in humans and some quite different. In this review
      we identify the most prominent of these barriers, discuss differences between rs
      fMRI in rodents and in humans, highlight best practices for animal studies, and
      review selected applications of rs-fMRI in rodents. Our goal is to facilitate the
      integration of human and animal work to the benefit of both fields. 

PMID- 26300721
TI  - Olfactory instruction for fear: neural system analysis.
AB  - Different types of predator odors engage elements of the hypothalamic predator
      responsive circuit, which has been largely investigated in studies using cat odor
      exposure. Studies using cat odor have led to detailed mapping of the neural sites
      involved in innate and contextual fear responses. Here, we reviewed three lines
      of work examining the dynamics of the neural systems that organize innate and
      learned fear responses to cat odor. In the first section, we explored the neural
      systems involved in innate fear responses and in the acquisition and expression
      of fear conditioning to cat odor, with a particular emphasis on the role of the
      dorsal premammillary nucleus (PMd) and the dorsolateral periaqueductal gray
      (PAGdl), which are key sites that influence innate fear and contextual
      conditioning. In the second section, we reviewed how chemical stimulation of the
      PMd and PAGdl may serve as a useful unconditioned stimulus in an olfactory fear
      conditioning paradigm; these experiments provide an interesting perspective for
      the understanding of learned fear to predator odor. Finally, in the third
      section, we explored the fact that neutral odors that acquire an aversive valence
      in a shock-paired conditioning paradigm may mimic predator odor and mobilize
      elements of the hypothalamic predator-responsive circuit. 

PMID- 26300722
TI  - Repeated vapor ethanol exposure induces transient histone modifications in the
      brain that are modified by genotype and brain region.
AB  - BACKGROUND: Emerging research implicates ethanol (EtOH)-induced epigenetic
      modifications in regulating gene expression and EtOH consumption. However,
      consensus on specific epigenetic modifications induced by EtOH has not yet
      emerged, making it challenging to identify mechanisms and develop targeted
      treatments. We hypothesized that chronic intermittent EtOH (CIE) induces
      persistent changes in histone modifications across the cerebral cortex (CCx),
      nucleus accumbens (NAc), and prefrontal cortex (PFC), and that these histone
      modifications are altered in a knock-in mouse strain with altered sensitivity to
      EtOH. METHODS: C57BL/6J (B6) mice and alpha1SHLA knockin mice on a B6 background
      were exposed to 16 h of vapor EtOH or room air followed by 8 h of room air for 4
      consecutive days and sacrificed at multiple time points up to 72 h following
      exposure. Histone modifications were assessed using Western blot and dot blot. RT
      qPCR was used to study expression of chromatin modifying enzymes in NAc and PFC.
      RESULTS: In NAc, CIE significantly increased acetylation of histone subunit H3 at
      lysine 9 (H3K9ac) but not lysine 14 (H3K14ac) or lysine 27 (H3K27ac). In PFC, CIE
      significantly increased H3K9ac but not H3K14 or H3K27ac. There were no
      significant changes at 8 or 72 h after EtOH exposure in either NAc or PFC. CIE
      was also associated with increased expression of Kat2b, Kat5, and Tet1 in NAc but
      not PFC. In CCx, CIE had a significant effect on levels of H3K18ac; there was
      also a significant effect of the alpha1SHLA mutation on levels of H3K27me3,
      H3K14ac, and H3K18ac as well as a trend for H3S10pK14ac. CONCLUSIONS: The EtOH
      induced histone modifications observed were transient and varied significantly
      between brain regions. A genetic mutation that altered sensitivity to EtOH was
      associated with altered induction of histone modifications during CIE. These
      results have implications for studying EtOH-induced histone modifications and
      EtOH sensitivity.

PMID- 26300723
TI  - Gene-environment interaction in programming hippocampal plasticity: focus on
      adult neurogenesis.
AB  - Interactions between genes and environment are a critical feature of development
      and both contribute to shape individuality. They are at the core of vulnerability
      resiliency for mental illnesses. During the early postnatal period, several brain
      structures involved in cognitive and emotional processing, such as the
      hippocampus, still develop and it is likely that interferences with this neuronal
      development, which is genetically determined, might lead to long-lasting
      structural and functional consequences and increase the risk of developing
      psychopathology. One particular target is adult neurogenesis, which is involved
      in the regulation of cognitive and emotional processes. Insights into the dynamic
      interplay between genes and environmental factors in setting up individual rates
      of neurogenesis have come from laboratory studies exploring experience-dependent
      changes in adult neurogenesis as a function of individual's genetic makeup. These
      studies have implications for our understanding of the mechanisms regulating
      adult neurogenesis, which could constitute a link between environmental
      challenges and psychopathology. 

PMID- 26300724
TI  - Dynamical properties of gene regulatory networks involved in long-term
      potentiation.
AB  - The long-lasting enhancement of synaptic effectiveness known as long-term
      potentiation (LTP) is considered to be the cellular basis of long-term memory.
      LTP elicits changes at the cellular and molecular level, including temporally
      specific alterations in gene networks. LTP can be seen as a biological process in
      which a transient signal sets a new homeostatic state that is "remembered" by
      cellular regulatory systems. Previously, we have shown that early growth response
      (Egr) transcription factors are of fundamental importance to gene networks
      recruited early after LTP induction. From a systems perspective, we hypothesized
      that these networks will show less stable architecture, while networks recruited
      later will exhibit increased stability, being more directly related to LTP
      consolidation. Using random Boolean network (RBN) simulations we found that the
      network derived at 24 h was markedly more stable than those derived at 20 min or
      5 h post-LTP. This temporal effect on the vulnerability of the networks is
      mirrored by what is known about the vulnerability of LTP and memory itself.
      Differential gene co-expression analysis further highlighted the importance of
      the Egr family and found a rapid enrichment in connectivity at 20 min, followed
      by a systematic decrease, providing a potential explanation for the down
      regulation of gene expression at 24 h documented in our preceding studies. We
      also found that the architecture exhibited by a control and the 24 h LTP co
      expression networks fit well to a scale-free distribution, known to be robust
      against perturbations. By contrast the 20 min and 5 h networks showed more
      truncated distributions. These results suggest that a new homeostatic state is
      achieved 24 h post-LTP. Together, these data present an integrated view of the
      genomic response following LTP induction by which the stability of the networks
      regulated at different times parallel the properties observed at the synapse. 

PMID- 26300726
TI  - Real-time imaging of bHLH transcription factors reveals their dynamic control in
      the multipotency and fate choice of neural stem cells.
AB  - The basic-helix-loop-helix (bHLH) transcription factors Ascl1/Mash1, Hes1, and
      Olig2 regulate the fate choice of neurons, astrocytes, and oligodendrocytes,
      respectively; however, these factors are coexpressed in self-renewing multipotent
      neural stem cells (NSCs) even before cell fate determination. This fact raises
      the possibility that these fate determination factors are differentially
      expressed between self-renewing and differentiating NSCs with unique expression
      dynamics. Real-time imaging analysis utilizing fluorescent proteins is a powerful
      strategy for monitoring expression dynamics. Fusion with fluorescent reporters
      makes it possible to analyze the dynamic behavior of specific proteins in living
      cells. However, it is technically challenging to conduct long-term imaging of
      proteins, particularly those with low expression levels, because a high
      sensitivity and low-noise imaging system is required, and very often bleaching of
      fluorescent proteins and cell toxicity by prolonged laser exposure are
      problematic. Furthermore, to analyze the functional roles of the dynamic
      expression of cellular proteins, it is essential to image reporter fusion
      proteins that are expressed at comparable levels to their endogenous expression.
      In this review, we introduce our recent reports about the dynamic control of bHLH
      transcription factors in multipotency and fate choice of NSCs, focusing on real
      time imaging of fluorescent reporters fused with bHLH transcription factors. Our
      imaging results indicate that bHLH transcription factors are expressed in an
      oscillatory manner by NSCs, and that one of them becomes dominant during fate
      choice. We propose that the multipotent state of NSCs correlates with the
      oscillatory expression of several bHLH transcription factors, whereas the
      differentiated state correlates with the sustained expression of a single bHLH
      transcription factor. 

PMID- 26300725
TI  - What makes a RAG regeneration associated?
AB  - Regenerative failure remains a significant barrier for functional recovery after
      central nervous system (CNS) injury. As such, understanding the physiological
      processes that regulate axon regeneration is a central focus of regenerative
      medicine. Studying the gene transcription responses to axon injury of
      regeneration competent neurons, such as those of the peripheral nervous system
      (PNS), has provided insight into the genes associated with regeneration. Though
      several individual "regeneration-associated genes" (RAGs) have been identified
      from these studies, the response to injury likely regulates the expression of
      functionally coordinated and complementary gene groups. For instance, successful
      regeneration would require the induction of genes that drive the intrinsic growth
      capacity of neurons, while simultaneously downregulating the genes that convey
      environmental inhibitory cues. Thus, this view emphasizes the transcriptional
      regulation of gene "programs" that contribute to the overall goal of axonal
      regeneration. Here, we review the known RAGs, focusing on how their
      transcriptional regulation can reveal the underlying gene programs that drive a
      regenerative phenotype. Finally, we will discuss paradigms under which we can
      determine whether these genes are injury-associated, or indeed necessary for
      regeneration. 

PMID- 26300728
TI  - GABAA receptor activity shapes the formation of inhibitory synapses between
      developing medium spiny neurons.
AB  - Basal ganglia play an essential role in motor coordination and cognitive
      functions. The GABAergic medium spiny neurons (MSNs) account for ~95% of all the
      neurons in this brain region. Central to the normal functioning of MSNs is
      integration of synaptic activity arriving from the glutamatergic corticostriatal
      and thalamostriatal afferents, with synaptic inhibition mediated by local
      interneurons and MSN axon collaterals. In this study we have investigated how the
      specific types of GABAergic synapses between the MSNs develop over time, and how
      the activity of GABAA receptors (GABAARs) influences this development. Isolated
      embryonic (E17) MSNs form a homogenous population in vitro and display
      spontaneous synaptic activity and functional properties similar to their in vivo
      counterparts. In dual whole-cell recordings of synaptically connected pairs of
      MSNs, action potential (AP)-activated synaptic events were detected between 7 and
      14 days in vitro (DIV), which coincided with the shift in GABAAR operation from
      depolarization to hyperpolarization, as detected indirectly by intracellular
      calcium imaging. In parallel, the predominant subtypes of inhibitory synapses,
      which innervate dendrites of MSNs and contain GABAAR alpha1 or alpha2 subunits,
      underwent distinct changes in the size of postsynaptic clusters, with alpha1
      becoming smaller and alpha2 larger over time, while both the percentage and the
      size of mixed alpha1/alpha2-postsynaptic clusters were increased. When activity
      of GABAARs was under chronic blockade between 4-7 DIV, the structural properties
      of these synapses remained unchanged. In contrast, chronic inhibition of GABAARs
      between 7-14 DIV led to reduction in size of alpha1- and alpha1/alpha2
      postsynaptic clusters and a concomitant increase in number and size of alpha2
      postsynaptic clusters. Thus, the main subtypes of GABAergic synapses formed by
      MSNs are regulated by GABAAR activity, but in opposite directions, and thus
      appear to be driven by different molecular mechanisms. 

PMID- 26300729
TI  - Stretch induced hyperexcitability of mice callosal pathway.
AB  - Memory and learning are thought to result from changes in synaptic strength.
      Previous studies on synaptic physiology in brain slices have traditionally been
      focused on biochemical processes. Here, we demonstrate with experiments on mouse
      brain slices that central nervous system plasticity is also sensitive to
      mechanical stretch. This is important, given the host of clinical conditions
      involving changes in mechanical tension on the brain, and the normal role that
      mechanical tension plays in brain development. A novel platform is developed to
      investigate neural responses to mechanical stretching. Flavoprotein
      autofluoresence (FA) imaging was employed for measuring neural activity. We
      observed that synaptic excitability substantially increases after a small (2.5%)
      stretch was held for 10 min and released. The increase is accumulative, i.e.,
      multiple stretch cycles further increase the excitability. We also developed
      analytical tools to quantify the spatial spread and response strength. Results
      show that the spatial spread is less stable in slices undergoing the stretch
      unstretch cycle. FA amplitude and activation rate decrease as excitability
      increases in stretch cases but not in electrically enhanced cases. These results
      collectively demonstrate that a small stretch in physiological range can modulate
      neural activities significantly, suggesting that mechanical events can be
      employed as a novel tool for the modulation of neural plasticity. 

PMID- 26300727
TI  - Gene expression profiling for human iPS-derived motor neurons from sporadic ALS
      patients reveals a strong association between mitochondrial functions and
      neurodegeneration.
AB  - Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that
      leads to widespread motor neuron death, general palsy and respiratory failure.
      The most prevalent sporadic ALS form is not genetically inherited. Attempts to
      translate therapeutic strategies have failed because the described mechanisms of
      disease are based on animal models carrying specific gene mutations and thus do
      not address sporadic ALS. In order to achieve a better approach to study the
      human disease, human induced pluripotent stem cell (hiPSC)-differentiated motor
      neurons were obtained from motor nerve fibroblasts of sporadic ALS and non-ALS
      subjects using the STEMCCA Cre-Excisable Constitutive Polycistronic Lentivirus
      system and submitted to microarray analyses using a whole human genome platform.
      DAVID analyses of differentially expressed genes identified molecular function
      and biological process-related genes through Gene Ontology. REVIGO highlighted
      the related functions mRNA and DNA binding, GTP binding, transcription (co)
      repressor activity, lipoprotein receptor binding, synapse organization,
      intracellular transport, mitotic cell cycle and cell death. KEGG showed pathways
      associated with Parkinson's disease and oxidative phosphorylation, highlighting
      iron homeostasis, neurotrophic functions, endosomal trafficking and ERK
      signaling. The analysis of most dysregulated genes and those representative of
      the majority of categorized genes indicates a strong association between
      mitochondrial function and cellular processes possibly related to motor neuron
      degeneration. In conclusion, iPSC-derived motor neurons from motor nerve
      fibroblasts of sporadic ALS patients may recapitulate key mechanisms of
      neurodegeneration and may offer an opportunity for translational investigation of
      sporadic ALS. Large gene profiling of differentiated motor neurons from sporadic
      ALS patients highlights mitochondrial participation in the establishment of
      autonomous mechanisms associated with sporadic ALS. 

PMID- 26300730
TI  - Fetal microglial phenotype in vitro carries memory of prior in vivo exposure to
      inflammation.
AB  - OBJECTIVE: Neuroinflammation in utero may result in life-long neurological
      disabilities. The molecular mechanisms whereby microglia contribute to this
      response remain incompletely understood. METHODS: Lipopolysaccharide (LPS) or
      saline were administered intravenously to non-anesthetized chronically
      instrumented near-term fetal sheep to model fetal inflammation in vivo. Microglia
      were then isolated from in vivo LPS and saline (naive) exposed animals. To mimic
      the second hit of neuroinflammation, these microglia were then re-exposed to LPS
      in vitro. Cytokine responses were measured in vivo and subsequently in vitro in
      the primary microglia cultures derived from these animals. We sequenced the whole
      transcriptome of naive and second hit microglia and profiled their genetic
      expression to define molecular pathways disrupted during neuroinflammation.
      RESULTS: In vivo LPS exposure resulted in IL-6 increase in fetal plasma 3 h post
      LPS exposure. Even though not histologically apparent, microglia acquired a pro
      inflammatory phenotype in vivo that was sustained and amplified in vitro upon
      second hit LPS exposure as measured by IL-1beta response in vitro and RNAseq
      analyses. While NFKB and Jak-Stat inflammatory pathways were up regulated in
      naive microglia, heme oxygenase 1 (HMOX1) and Fructose-1,6-bisphosphatase (FBP)
      genes were uniquely differentially expressed in the second hit microglia.
      Compared to the microglia exposed to LPS in vitro only, the transcriptome of the
      in vivo LPS pre-exposed microglia showed a diminished differential gene
      expression in inflammatory and metabolic pathways prior and upon re-exposure to
      LPS in vitro. Notably, this desensitization response was also observed in histone
      deacetylases (HDAC) 1, 2, 4, and 6. Microglial calreticulin/LRP genes implicated
      in microglia-neuronal communication relevant for the neuronal development were up
      regulated in second hit microglia. DISCUSSION: We identified a unique HMOX1 down
      and FBP (up) phenotype of microglia exposed to the double-hit suggesting
      interplay of inflammatory and metabolic pathways. Our findings suggest that
      epigenetic mechanisms mediate this immunological and metabolic memory of the
      prior inflammatory insult relevant to neuronal development and provide new
      therapeutic targets for early postnatal intervention to prevent brain injury.

PMID- 26300731
TI  - Role of T cell-glial cell interactions in creating and amplifying central nervous
      system inflammation and multiple sclerosis disease symptoms.
AB  - Multiple Sclerosis (MS) is an inflammatory disease of the Central Nervous System
      (CNS) that causes the demyelination of nerve cells and destroys oligodendrocytes,
      neurons and axons. Historically, MS has been thought of as a T cell-mediated
      autoimmune disease of CNS white matter. However, recent studies have identified
      gray matter lesions in MS patients, suggesting that CNS antigens other than
      myelin proteins may be involved during the MS disease process. We have recently
      found that T cells targeting astrocyte-specific antigens can drive unique aspects
      of inflammatory CNS autoimmunity, including the targeting of gray matter and
      white matter of the brain and inducing heterogeneous clinical disease courses. In
      addition to being a target of T cells, astrocytes play a critical role in
      propagating the inflammatory response within the CNS induced NF-kappaB signaling.
      Here, we will discuss the pathophysiology of CNS inflammation mediated by T cell
      glial cell interactions and its contributions to CNS autoimmunity. 

PMID- 26300732
TI  - Monomeric beta-amyloid interacts with type-1 insulin-like growth factor receptors
      to provide energy supply to neurons.
AB  - beta-amyloid (Abeta1-42) is produced by proteolytic cleavage of the transmembrane
      type-1 protein, amyloid precursor protein. Under pathological conditions, Abeta1
      42self-aggregates into oligomers, which cause synaptic dysfunction and neuronal
      loss, and are considered the culprit of Alzheimer's disease (AD). However, Abeta1
      42 is mainly monomeric at physiological concentrations, and the precise role of
      monomeric Abeta1-42 in neuronal function is largely unknown. We report that the
      monomer of Abeta1-42 activates type-1 insulin-like growth factor receptors and
      enhances glucose uptake in neurons and peripheral cells by promoting the
      translocation of the Glut3 glucose transporter from the cytosol to the plasma
      membrane. In neurons, activity-dependent glucose uptake was blunted after
      blocking endogenous Abeta production, and re-established in the presence of
      cerebrospinal fluid Abeta. APP-null neurons failed to enhance depolarization
      stimulated glucose uptake unless exogenous monomeric Abeta1-42 was added. These
      data suggest that Abeta1-42 monomers were critical for maintaining neuronal
      glucose homeostasis. Accordingly, exogenous Abeta1-42 monomers were able to
      rescue the low levels of glucose consumption observed in brain slices from AD
      mutant mice. 

PMID- 26300733
TI  - Methylcobalamin promotes the differentiation of Schwann cells and remyelination
      in lysophosphatidylcholine-induced demyelination of the rat sciatic nerve.
AB  - Schwann cells (SCs) are constituents of the peripheral nervous system. The
      differentiation of SCs in injured peripheral nerves is critical for regeneration
      after injury. Methylcobalamin (MeCbl) is a vitamin B12 analog that is necessary
      for the maintenance of the peripheral nervous system. In this study, we estimated
      the effect of MeCbl on SCs. We showed that MeCbl downregulated the activity of
      Erk1/2 and promoted the expression of the myelin basic protein in SCs. In a
      dorsal root ganglion neuron-SC coculture system, myelination was promoted by
      MeCbl. In a focal demyelination rat model, MeCbl promoted remyelination and motor
      and sensory functional regeneration. MeCbl promoted the in vitro differentiation
      of SCs and in vivo myelination in a rat demyelination model and may be a novel
      therapy for several types of nervous disorders. 

PMID- 26300734
TI  - The neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)) alters hippocampal excitatory
      synaptic transmission by modulation of the GABAergic system.
AB  - The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces
      Parkinson's disease-like symptoms following administration to mice, monkeys, and
      humans. A common view is that MPTP is metabolized to 1-methyl-4-phenylpyridinium
      ion (MPP(+)) to induce its neurodegenerative effects on dopaminergic neurons in
      the substantia nigra (SN). Moreover, the hippocampus contains dopaminergic
      fibers, which are projecting from the ventral tegmental area, SN and pars
      compacta and contain the whole machinery required for dopamine synthesis making
      them sensitive to MPTP and MPP(+). Here, we present data showing that acute bath
      application of MPP(+) elicited a dose-dependent facilitation followed by a
      depression of synaptic transmission of hippocampal Schaffer collaterals-CA1
      synapses in mice. The effects of MPP(+) were not mediated by D1/D5- and D2-like
      receptor activation. Inhibition of the dopamine transporters did not prevent but
      increased the depression of excitatory post-synaptic field potentials. In the
      search for a possible mechanism, we observed that MPP(+) reduced the appearance
      of polyspikes in population spikes recorded in str. pyramidale and increased the
      frequency of miniature inhibitory post-synaptic currents. The acute effect of
      MPP(+) on synaptic transmission was attenuated by co-application of a GABAA
      receptor antagonist. Taking these data together, we suggest that MPP(+) affects
      hippocampal synaptic transmission by enhancing some aspects of the hippocampal
      GABAergic system. 

PMID- 26300735
TI  - Editorial: Mechanisms of neuroinflammation and inflammatory neurodegeneration in
      acute brain injury.

PMID- 26300736
TI  - Maternal immune activation evoked by polyinosinic:polycytidylic acid does not
      evoke microglial cell activation in the embryo.
AB  - Several studies have indicated that inflammation during pregnancy increases the
      risk for the development of neuropsychiatric disorders in the offspring.
      Morphological brain abnormalities combined with deviations in the inflammatory
      status of the brain can be observed in patients of both autism and schizophrenia.
      It was shown that acute infection can induce changes in maternal cytokine levels
      which in turn are suggested to affect fetal brain development and increase the
      risk on the development of neuropsychiatric disorders in the offspring. Animal
      models of maternal immune activation reproduce the etiology of neurodevelopmental
      disorders such as schizophrenia and autism. In this study the poly (I:C) model
      was used to mimic viral immune activation in pregnant mice in order to assess the
      activation status of fetal microglia in these developmental disorders. Because
      microglia are the resident immune cells of the brain they were expected to be
      activated due to the inflammatory stimulus. Microglial cell density and
      activation level in the fetal cortex and hippocampus were determined. Despite the
      presence of a systemic inflammation in the pregnant mice, there was no
      significant difference in fetal microglial cell density or immunohistochemically
      determined activation level between the control and inflammation group. These
      data indicate that activation of the fetal microglial cells is not likely to be
      responsible for the inflammation induced deficits in the offspring in this model.

PMID- 26300737
TI  - Sympathoadrenergic modulation of hematopoiesis: a review of available evidence
      and of therapeutic perspectives.
AB  - Innervation of the bone marrow (BM) has been described more than one century ago,
      however the first in vivo evidence that sympathoadrenergic fibers have a role in
      hematopoiesis dates back to less than 25 years ago. Evidence has since increased
      showing that adrenergic nerves in the BM release noradrenaline and possibly also
      dopamine, which act on adrenoceptors and dopaminergic receptors (DR) expressed on
      hematopoietic cells and affect cell survival, proliferation, migration and
      engraftment ability. Remarkably, dysregulation of adrenergic fibers to the BM is
      associated with hematopoietic disturbances and myeloproliferative disease.
      Several adrenergic and dopaminergic agents are already in clinical use for non
      hematological indications and with a usually favorable risk-benefit profile, and
      are therefore potential candidates for non-conventional modulation of
      hematopoiesis. 

PMID- 26300738
TI  - Model-based analysis of pattern motion processing in mouse primary visual cortex.
AB  - Neurons in sensory areas of neocortex exhibit responses tuned to specific
      features of the environment. In visual cortex, information about features such as
      edges or textures with particular orientations must be integrated to recognize a
      visual scene or object. Connectivity studies in rodent cortex have revealed that
      neurons make specific connections within sub-networks sharing common input
      tuning. In principle, this sub-network architecture enables local cortical
      circuits to integrate sensory information. However, whether feature integration
      indeed occurs locally in rodent primary sensory areas has not been examined
      directly. We studied local integration of sensory features in primary visual
      cortex (V1) of the mouse by presenting drifting grating and plaid stimuli, while
      recording the activity of neuronal populations with two-photon calcium imaging.
      Using a Bayesian model-based analysis framework, we classified single-cell
      responses as being selective for either individual grating components or for
      moving plaid patterns. Rather than relying on trial-averaged responses, our model
      based framework takes into account single-trial responses and can easily be
      extended to consider any number of arbitrary predictive models. Our analysis
      method was able to successfully classify significantly more responses than
      traditional partial correlation (PC) analysis, and provides a rigorous
      statistical framework to rank any number of models and reject poorly performing
      models. We also found a large proportion of cells that respond strongly to only
      one stimulus class. In addition, a quarter of selectively responding neurons had
      more complex responses that could not be explained by any simple integration
      model. Our results show that a broad range of pattern integration processes
      already take place at the level of V1. This diversity of integration is
      consistent with processing of visual inputs by local sub-networks within V1 that
      are tuned to combinations of sensory features. 

PMID- 26300739
TI  - Preservation of the optic radiations based on comparative analysis of diffusion
      tensor imaging tractography and anatomical dissection.
AB  - BACKGROUND: Visualization of the precise course of the visual pathways is
      relevant to prevent damage that may inflict visual field deficits during
      neurosurgical resections. In particular the optic radiations (OR) are susceptible
      to such damage during neurosurgery. Cortical pathways can be mapped in vivo, by
      using Diffusion Tensor Imaging (DTI). Visualization of these pathways would be
      potentially helpful to prevent neurosurgical visual morbidity. In this study an
      anatomical dissection of the visual pathways was compared to DTI fiber
      tractography (DTI-FT) data of four human brains. The feasibility of a definition
      of a Safety Zone is investigated. METHODS: Four adult brains were dissected using
      Klingler's fiber dissection method, which allowed preparation of the OR.
      Measurements before and after dissection were used to establish distances from
      the cortex to the OR. DTI-scans were also obtained from these brains to determine
      the same distances. RESULTS: Measurements from specific landmark points on the
      cortex to the lateral border of the OR were performed in four brains. Analysis
      through DTI tractography corresponded with the dissection results. Based on the
      combined results of both dissection and DTI-FT, we defined a quantitative
      surgical Safety Zone with respect to various anatomical landmarks (in particular
      the ventricle system). CONCLUSION: We conclude that there is a good correlation
      between the visualizations of the optic pathways based on dissection and DTI.
      Furthermore, we conclude that defining a neurosurgical Safety Zone which could
      preserve the integrity of the OR during surgery, based on the combination of DTI
      FT images and dissection is feasible.

PMID- 26300740
TI  - Habitual behavior and dopamine cell vulnerability in Parkinson disease.

PMID- 26300741
TI  - Calcium-binding protein immunoreactivity in Gudden's tegmental nuclei and the
      hippocampal formation: differential co-localization in neurons projecting to the
      mammillary bodies.
AB  - The principal projections to the mammillary bodies arise from just two sites,
      Gudden's tegmental nuclei (dorsal and ventral nuclei) and the hippocampal
      formation (subiculum and pre/postsubiculum). The present study sought to compare
      the neurochemical properties of these mammillary body inputs in the rat, with a
      focus on calcium-binding proteins. Neuronal calretinin (CR) immunoreactivity was
      sparse in Gudden's tegmental nuclei and showed no co-localization with neurons
      projecting to the mammillary bodies. In contrast, many of the ventral tegmental
      nucleus of Gudden cell that project to the mammillary bodies were parvalbumin
      (PV)-positive whereas a smaller number of mammillary inputs stained for calbindin
      (CB). Only a few mammillary body projection cells in the dorsal tegmental nucleus
      of Gudden co-localized with PV and none co-localized with CB. A very different
      pattern was found in the hippocampal formation. Here, a large proportion of
      postsubiculum cells that project to the mammillary bodies co-localized with CR,
      but not CB or PV. While many neurons in the dorsal and ventral subiculum
      projected to the mammillary bodies, these cells did not co-localize with the
      immunofluorescence of any of the three tested proteins. These findings highlight
      marked differences between hippocampal and tegmental inputs to the rat mammillary
      bodies as well as differences between the medial and lateral mammillary systems.
      These findings also indicate some conserved neurochemical properties in Gudden's
      tegmental nuclei across rodents and primates. 

PMID- 26300742
TI  - Differential myelinated and unmyelinated sensory and autonomic skin nerve fiber
      involvement in patients with ophthalmic postherpetic neuralgia.
AB  - Postherpetic neuralgia (PHN) is a common and exceptionally drug-resistant
      neuropathic pain condition. In this cross-sectional skin biopsy study, seeking
      information on the responsible pathophysiological mechanisms we assessed how
      ophthalmic PHN affects sensory and autonomic skin innervation. We took 2-mm
      supraorbital punch skin biopsies from the affected and unaffected sides in 10
      patients with ophthalmic PHN. Using indirect immunofluorescence and a large panel
      of antibodies including protein gene product (PGP) 9.5 we quantified epidermal
      unmyelinated, dermal myelinated and autonomic nerve fibers. Although skin biopsy
      showed reduced epidermal and dermal myelinated fiber density in specimens from
      the affected side, the epidermal/dermal myelinated nerve fiber ratio was lower in
      the affected than in the unaffected side (p < 0.001), thus suggesting a
      predominant epidermal unmyelinated nerve fiber loss. Conversely, autonomic skin
      innervation was spared. Our study showing that ophthalmic PHN predominantly
      affects unmyelinated nerve fiber and spares autonomic nerve fiber might help to
      understand the pathophysiological mechanisms underlying this difficult-to-treat
      condition. 

PMID- 26300743
TI  - Improvements in dizziness and imbalance results from using a multi disciplinary
      and multi sensory approach to Vestibular Physical Therapy - a case study.
AB  - This paper discusses a case study of a 41-year-old active duty male service
      member who sustained head trauma from a motorcycle accident and underwent
      multidisciplinary vestibular physical therapy rehabilitation. He was initially
      treated with traditional physical therapy applications of treadmill walking and
      standing balance with some symptom improvements, but was not able to maintain a
      running speed that would allow him to return to full active duty status. Further
      treatment utilizing a Computer Assisted Rehabilitation Environment was performed
      in order to increase level of difficulty and further enhance function. This
      treatment is able to elicit vestibular deficits seen in the community as it
      requires subjects to walk and balance while performing tasks within a virtual
      scenario incorporating platform motion, visual surround and flow, and cognitive
      processing. After 6 weeks of therapy, twice weekly, improvements in clinical
      vestibular measures were observed as well as walking speed and patient
      confidence. The patient was able to return to full duty after treatment. This
      case study provides supportive evidence that multidimensional tasking in a
      virtual environment provides a safe but demanding form of vestibular therapy for
      patients needing more challenging tasks than those provided with traditional
      therapy techniques. Those persons requiring higher levels of performance before
      returning to full duty (e.g., pilots, special operators, etc.) may find this type
      of therapy beneficial. 

PMID- 26300744
TI  - Network models provide insights into how oriens-lacunosum-moleculare and
      bistratified cell interactions influence the power of local hippocampal CA1 theta
      oscillations.
AB  - Hippocampal theta is a 4-12 Hz rhythm associated with episodic memory, and
      although it has been studied extensively, the cellular mechanisms underlying its
      generation are unclear. The complex interactions between different interneuron
      types, such as those between oriens-lacunosum-moleculare (OLM) interneurons and
      bistratified cells (BiCs), make their contribution to network rhythms difficult
      to determine experimentally. We created network models that are tied to
      experimental work at both cellular and network levels to explore how these
      interneuron interactions affect the power of local oscillations. Our cellular
      models were constrained with properties from patch clamp recordings in the CA1
      region of an intact hippocampus preparation in vitro. Our network models are
      composed of three different types of interneurons: parvalbumin-positive (PV+)
      basket and axo-axonic cells (BC/AACs), PV+ BiCs, and somatostatin-positive OLM
      cells. Also included is a spatially extended pyramidal cell model to allow for a
      simplified local field potential representation, as well as experimentally
      constrained, theta frequency synaptic inputs to the interneurons. The network
      size, connectivity, and synaptic properties were constrained with experimental
      data. To determine how the interactions between OLM cells and BiCs could affect
      local theta power, we explored how the number of OLM-BiC connections and
      connection strength affected local theta power. We found that our models operate
      in regimes that could be distinguished by whether OLM cells minimally or strongly
      affected the power of network theta oscillations due to balances that,
      respectively, allow compensatory effects or not. Inactivation of OLM cells could
      result in no change or even an increase in theta power. We predict that the dis
      inhibitory effect of OLM cells to BiCs to pyramidal cell interactions plays a
      critical role in the resulting power of network theta oscillations. Overall, our
      network models reveal a dynamic interplay between different classes of
      interneurons in influencing local theta power. 

PMID- 26300747
TI  - The framing effect and skin conductance responses.
AB  - Individuals often rely on simple heuristics when they face complex choice
      situations under uncertainty. Traditionally, it has been proposed that cognitive
      processes are the main driver to evaluate different choice options and to finally
      reach a decision. Growing evidence, however, highlights a strong interrelation
      between judgment and decision-making (JDM) on the one hand, and emotional
      processes on the other hand. This also seems to apply to judgmental heuristics,
      i.e., decision processes that are typically considered to be fast and intuitive.
      In this study, participants are exposed to different probabilities of receiving
      an unpleasant electric shock. Information about electric shock probabilities is
      either positively or negatively framed. Integrated skin conductance responses
      (ISCRs) while waiting for electric shock realization are used as an indicator for
      participants' emotional arousal. This measure is compared to objective
      probabilities. I find evidence for a relation between emotional body reactions
      measured by ISCRs and the framing effect. Under negative frames, participants
      show significantly higher ISCRs while waiting for an electric shock to be
      delivered than under positive frames. This result might contribute to a better
      understanding of the psychological processes underlying JDM. Further studies are
      necessary to reveal the causality underlying this finding, i.e., whether
      emotional processes influence JDM or vice versa. 

PMID- 26300746
TI  - Plasticity of cerebellar Purkinje cells in behavioral training of body balance
      control.
AB  - Neural responses to sensory inputs caused by self-generated movements
      (reafference) and external passive stimulation (exafference) differ in various
      brain regions. The ability to differentiate such sensory information can lead to
      movement execution with better accuracy. However, how sensory responses are
      adjusted in regard to this distinguishability during motor learning is still
      poorly understood. The cerebellum has been hypothesized to analyze the functional
      significance of sensory information during motor learning, and is thought to be a
      key region of reafference computation in the vestibular system. In this study, we
      investigated Purkinje cell (PC) spike trains as cerebellar cortical output when
      rats learned to balance on a suspended dowel. Rats progressively reduced the
      amplitude of body swing and made fewer foot slips during a 5-min balancing task.
      Both PC simple (SSs; 17 of 26) and complex spikes (CSs; 7 of 12) were found to
      code initially on the angle of the heads with respect to a fixed reference. Using
      periods with comparable degrees of movement, we found that such SS coding of
      information in most PCs (10 of 17) decreased rapidly during balance learning. In
      response to unexpected perturbations and under anesthesia, SS coding capability
      of these PCs recovered. By plotting SS and CS firing frequencies over 15-s time
      windows in double-logarithmic plots, a negative correlation between SS and CS was
      found in awake, but not anesthetized, rats. PCs with prominent SS coding
      attenuation during motor learning showed weaker SS-CS correlation. Hence, we
      demonstrate that neural plasticity for filtering out sensory reafference from
      active motion occurs in the cerebellar cortex in rats during balance learning. SS
      CS interaction may contribute to this rapid plasticity as a form of receptive
      field plasticity in the cerebellar cortex between two receptive maps of sensory
      inputs from the external world and of efference copies from the will center for
      volitional movements. 

PMID- 26300748
TI  - Social defeat-induced anhedonia: effects on operant sucrose-seeking behavior.
AB  - Reduced capacity to experience pleasure, also known as anhedonia, is a key
      feature of the depressive state and is associated with poor disease prognosis and
      treatment outcome. Various behavioral readouts (e.g., reduced sucrose intake)
      have been employed in animal models of depression as a measure of anhedonia.
      However, several aspects of anhedonia are poorly represented within the
      repertoire of current preclinical assessments. We recently adopted the social
      defeat-induced persistent stress (SDPS) paradigm that models a maintained
      depressive-like state in the rat, including social withdrawal and deficits in
      short-term spatial memory. Here we investigated whether SDPS elicited persistent
      deficits in natural reward evaluation, as part of anhedonia. We examined cue
      paired operant sucrose self-administration, enabling us to study acquisition,
      motivation, extinction, and relapse to sucrose seeking following SDPS.
      Furthermore, we addressed whether guanfacine, an alpha2-adrenergic agonist that
      reduces stress-triggered maladaptive behavioral responses to drugs of abuse,
      could relief from SDPS-induced anhedonia. SDPS, consisting of five social defeat
      episodes followed by prolonged (>=8 weeks) social isolation, did not affect
      sucrose consumption during acquisition of self-administration. However, it
      strongly enhanced the motivational drive to acquire a sucrose reward in
      progressive ratio training. Moreover, SDPS induced initial resilience to
      extinction and rendered animals more sensitive to cue-induced reinstatement of
      sucrose-seeking. Guanfacine treatment attenuated SDPS-induced motivational
      overdrive and limited reinstatement of sucrose seeking, normalizing behavior to
      control levels. Together, our data indicate that long after the termination of
      stress exposure, SDPS induces guanfacine-reversible deficits in evaluation of a
      natural reward. Importantly, the SDPS-triggered anhedonia reflects many aspects
      of the human phenotype, including impaired motivation and goal-directed conduct. 

PMID- 26300745
TI  - Understanding how discrete populations of hypothalamic neurons orchestrate
      complicated behavioral states.
AB  - A major question in systems neuroscience is how a single population of neurons
      can interact with the rest of the brain to orchestrate complex behavioral states.
      The hypothalamus contains many such discrete neuronal populations that
      individually regulate arousal, feeding, and drinking. For example, hypothalamic
      neurons that express hypocretin (Hcrt) neuropeptides can sense homeostatic and
      metabolic factors affecting wakefulness and orchestrate organismal arousal.
      Neurons that express agouti-related protein (AgRP) can sense the metabolic needs
      of the body and orchestrate a state of hunger. The organum vasculosum of the
      lamina terminalis (OVLT) can detect the hypertonicity of blood and orchestrate a
      state of thirst. Each hypothalamic population is sufficient to generate
      complicated behavioral states through the combined efforts of distinct efferent
      projections. The principal challenge to understanding these brain systems is
      therefore to determine the individual roles of each downstream projection for
      each behavioral state. In recent years, the development and application of
      temporally precise, genetically encoded tools has greatly improved our
      understanding of the structure and function of these neural systems. This review
      will survey recent advances in our understanding of how these individual
      hypothalamic populations can orchestrate complicated behavioral states due to the
      combined efforts of individual downstream projections. 

PMID- 26300751
TI  - Specific olfactory neurons and glomeruli are associated to differences in
      behavioral responses to pheromone components between two Helicoverpa species.
AB  - Sex pheromone communication of moths helps to understand the mechanisms
      underlying reproductive isolation and speciation. Helicoverpa armigera and
      Helicoverpa assulta use (Z)-11-hexadecenal (Z11-16:Ald) and (Z)-9-hexadecenal (Z9
      16:Ald) as pheromone components in reversed ratios, 97:3 and 5:95, respectively.
      H. armigera also produces trace amount of (Z)-9-tetradecenal (Z9-14:Ald) in the
      sex pheromone gland, but H. assulta does not. Wind tunnel studies revealed that
      the addition of small amounts (0.3%) of Z9-14:Ald to the main pheromone blend of
      H. armigera increased the males' attraction, but at higher doses (1%, 10%) the
      same compound acted as an inhibitor. In H. assulta, Z9-14:Ald reduced male
      attraction when presented as 1% to the pheromone blend, but was ineffective at
      lower concentrations (0.3%). Three types (A-C) of sensilla trichodea in antennae
      were identified by single sensillum recording, responding to Z11-16:Ald, Z9
      14:Ald, and both Z9-16:Ald and Z9-14:Ald, respectively. Calcium imaging in the
      antennal lobes (ALs) revealed that the input information of the three chemicals
      was transmitted to three units of the macroglomerular complex (MGC) in ALs in
      both species: a large glomerulus for the major pheromone components, a small one
      for the minor pheromone components, and a third one for the behavioral
      antagonists. The type A and C neurons tuned to Z11-16:Ald and Z9-16:Ald had a
      reversed target in the MGC between the two species. In H. armigera, low doses (1,
      10 MUg) of Z9-14:Ald dominantly activated the glomerulus which processes the
      minor pheromone component, while a higher dose (100 MUg) also evoked an equal
      activity in the antagonistic glomerulus. In H. assulta, instead, Z9-14:Ald always
      strongly activated the antagonistic glomerulus. These results suggest that Z9
      14:Ald plays different roles in the sexual communication of two Helicoverpa
      species through activation of functionally different olfactory pathways. 

PMID- 26300750
TI  - Allopregnanolone in the bed nucleus of the stria terminalis modulates contextual
      fear in rats.
AB  - Trauma- and stress-related disorders are among the most common types of mental
      illness affecting the U.S. population. For many of these disorders, there is a
      striking sex difference in lifetime prevalence; for instance, women are twice as
      likely as men to be affected by posttraumatic stress disorder (PTSD). Gonadal
      steroids and their metabolites have been implicated in sex differences in fear
      and anxiety. One example, allopregnanolone (ALLO), is a neuroactive metabolite of
      progesterone that allosterically enhances GABAA receptor activity and has
      anxiolytic effects. Like other ovarian hormones, it not only occurs at different
      levels in males and females but also fluctuates over the female reproductive
      cycle. One brain structure that may be involved in neuroactive steroid regulation
      of fear and anxiety is the bed nucleus of the stria terminalis (BNST). To explore
      this question, we examined the consequences of augmenting or reducing ALLO
      activity in the BNST on the expression of Pavlovian fear conditioning in rats. In
      Experiment 1, intra-BNST infusions of ALLO in male rats suppressed freezing
      behavior (a fear response) to the conditioned context, but did not influence
      freezing to a discrete tone conditioned stimulus (CS). In Experiment 2, intra
      BNST infusion of either finasteride (FIN), an inhibitor of ALLO synthesis, or 17
      phenyl-(3alpha,5alpha)-androst-16-en-3-ol, an ALLO antagonist, in female rats
      enhanced contextual freezing; neither treatment affected freezing to the tone CS.
      These findings support a role for ALLO in modulating contextual fear via the BNST
      and suggest that sex differences in fear and anxiety could arise from
      differential steroid regulation of BNST function. The susceptibility of women to
      disorders such as PTSD may be linked to cyclic declines in neuroactive steroid
      activity within fear circuitry.

PMID- 26300749
TI  - Neuronal correlates of asocial behavior in a BTBR T (+) Itpr3(tf)/J mouse model
      of autism.
AB  - Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized, in
      part, by an inability to adequately respond to social cues. Patients diagnosed
      with ASD are often devoid of empathy and impaired in understanding other people's
      emotional perspective. The neuronal correlates of this impairment are not fully
      understood. Replicating such a behavioral phenotype in a mouse model of autism
      would allow us insight into the neuronal background of the problem. Here we
      tested BTBR T(+)Itpr3(tf)/J (BTBR) and c57BL/6J (B6) mice in two behavioral
      paradigms: the Transfer of Emotional Information test and the Social Proximity
      test. In both tests BTBR mice displayed asocial behavior. We analyzed c-Fos
      protein expression in several brain regions after each of these tests, and found
      that, unlike B6 mice, BTBR mice react to a stressed cagemate exposure in the
      Transfer of Emotional Information test with no increase of c-Fos expression in
      either the prefrontal cortex or the amygdala. However, after Social Proximity
      exposure we observed a strong increase in c-Fos expression in the CA3 field of
      the hippocampus and two hypothalamic regions of BTBR brains. This response was
      accompanied by a strong activation of periaqueductal regions related to
      defensiveness, which suggests that BTBR mice find unavoidable social interaction
      highly aversive. 

PMID- 26300752
TI  - Commentary: Chronic SSRI stimulation of astrocytic 5-HT2B receptors change
      multiple gene expressions/editings and metabolism of glutamate, glucose and
      glycogen: a potential paradigm shift.

PMID- 26300754
TI  - Neural correlates of error prediction in a complex motor task.
AB  - The goal of the study was to quantify error prediction processes via neural
      correlates in the Electroencephalogram (EEG). Access to such a neural signal will
      allow to gain insights into functional and temporal aspects of error perception
      in the course of learning. We focused on the error negativity (Ne) or error
      related negativity (ERN) as a candidate index for the prediction processes. We
      have used a virtual goal-oriented throwing task where participants used a lever
      to throw a virtual ball displayed on a computer monitor with the goal of hitting
      a virtual target as often as possible. After one day of practice with 400 trials,
      participants performed another 400 trials on a second day with EEG measurement.
      After error trials (i.e., when the ball missed the target), we found a sharp
      negative deflection in the EEG peaking 250 ms after ball release (mean amplitude:
      t = -2.5, df = 20, p = 0.02) and another broader negative deflection following
      the first, reaching from about 300 ms after release until unambiguous visual
      knowledge of results (KR; hitting or passing by the target; mean amplitude: t = 
      7.5, df = 20, p < 0.001). According to shape and timing of the two deflections,
      we assume that the first deflection represents a predictive Ne/ERN (prediction
      based on efferent commands and proprioceptive feedback) while the second
      deflection might have arisen from action monitoring. 

PMID- 26300753
TI  - Social cognition in children at familial high-risk of developing an eating
      disorder.
AB  - OBJECTIVE: Diagnosis of an eating disorder (ED) has been associated with
      differences in social cognition. To date research investigating social cognition
      and ED has mainly employed patient and recovered samples. It is therefore unclear
      whether differences in social cognition are present prior to onset of ED,
      potentially contributing to development, or whether differences observed are a
      consequence of the disorder. We aimed to further explore whether individuals at
      high-risk for ED present social cognition characteristics previously found in ED
      groups. METHODS: Our sample was drawn from a population-based cohort, the Avon
      Longitudinal Study of Parents and Children (ALSPAC). Data on maternal ED
      behaviors over the lifetime were collected through in-depth clinical interviews
      (n = 1128) conducted using the Structured Clinical Interview for DSM disorders
      (SCID), and were used to categorize mothers according to ED behaviors over the
      lifetime: Restricting and Excessive Exercising (n = 58), Purging (n = 70), Binge
      eating (n = 72), Binging and Purging (n = 66), no ED (n = 862). High-risk status
      of children was determined using these maternal lifetime behavioral phenotypes.
      Children at high-risk (maternal ED exposure) were compared to children at low
      risk (born to mothers with no ED) on three measures of social cognition: the
      Social Communication Disorders Checklist (SCDC) (n = 922), the faces subtest of
      the Diagnostic Analysis of Non-Verbal Accuracy (DANVA) (n = 722), and the
      Emotional Triangles Task (n = 750). RESULTS: Children at high-risk for ED showed
      poorer performance on measures of social cognition compared to children at low
      risk. Maternal lifetime binge-eating, and maternal lifetime binging and purging
      were associated with poorer social communication in children (OR: 2.4, 95% CI:
      1.0, 5.7, p = 0.05; and OR: 2.7, 95% CI: 1.1, 6.5, p = 0.03 respectively).
      Maternal binging and purging was also found to be associated with differential
      facial emotion processing and poorer recognition of fear from social motion cues
      (B: -0.7, 95% CI: -1.1, -0.2, p = 0.004). DISCUSSION: Children at high-risk for
      ED showed slight differences in some areas of social cognition when compared to
      children at low-risk. Characteristic patterns in social cognition are present in
      children at high-risk for ED, particularly among children whose mothers have
      binge-eating and purging behaviors over the lifetime. Our findings support the
      hypothesis that these differences may be part of an intermediate phenotype for
      ED: perhaps contributing to development, or perhaps indexing a shared liability
      with psychiatric disorders characterized by abnormal social cognition.

PMID- 26300755
TI  - Deployment of spatial attention without moving the eyes is boosted by oculomotor
      adaptation.
AB  - Vertebrates developed sophisticated solutions to select environmental visual
      information, being capable of moving attention without moving the eyes. A large
      body of behavioral and neuroimaging studies indicate a tight coupling between eye
      movements and spatial attention. The nature of this link, however, remains highly
      debated. Here, we demonstrate that deployment of human covert attention, measured
      in stationary eye conditions, can be boosted across space by changing the size of
      ocular saccades to a single position via a specific adaptation paradigm. These
      findings indicate that spatial attention is more widely affected by oculomotor
      plasticity than previously thought. 

PMID- 26300756
TI  - Deficits in reflexive covert attention following cerebellar injury.
AB  - Traditionally the cerebellum has been known for its important role in
      coordinating motor output. Over the past 15 years numerous studies have indicated
      that the cerebellum plays a role in a variety of cognitive functions including
      working memory, language, perceptual functions, and emotion. In addition, recent
      work suggests that regions of the cerebellum involved in eye movements also play
      a role in controlling covert visual attention. Here we investigated whether
      regions of the cerebellum that are not strictly tied to the control of eye
      movements might also contribute to covert attention. To address this question we
      examined the effects of circumscribed cerebellar lesions on reflexive covert
      attention in a group of patients (n = 11) without any gross motor or oculomotor
      deficits, and compared their performance to a group of age-matched controls (n =
      11). Results indicated that the traditional RT advantage for validly cued targets
      was significantly smaller at the shortest (50 ms) SOA for cerebellar patients
      compared to controls. Critically, a lesion overlap analysis indicated that this
      deficit in the rapid deployment of attention was linked to damage in Crus I and
      Crus II of the lateral cerebellum. Importantly, both cerebellar regions have
      connections to non-motor regions of the prefrontal and posterior parietal
      cortices-regions important for controlling visuospatial attention. Together,
      these data provide converging evidence that both lateral and midline regions of
      the cerebellum play an important role in the control of reflexive covert visual
      attention. 

PMID- 26300757
TI  - On the existence of a generalized non-specific task-dependent network.
AB  - In this paper we suggest the existence of a generalized task-related cortical
      network that is up-regulated whenever the task to be performed requires the
      allocation of generalized non-specific cognitive resources, independent of the
      specifics of the task to be performed. We have labeled this general purpose
      network, the extrinsic mode network (EMN) as complementary to the default mode
      network (DMN), such that the EMN is down-regulated during periods of task
      absence, when the DMN is up-regulated, and vice versa. We conceptualize the EMN
      as a cortical network for extrinsic neuronal activity, similar to the DMN as
      being a cortical network for intrinsic neuronal activity. The EMN has essentially
      a fronto-temporo-parietal spatial distribution, including the inferior and middle
      frontal gyri, inferior parietal lobule, supplementary motor area, inferior
      temporal gyrus. We hypothesize that this network is always active regardless of
      the cognitive task being performed. We further suggest that failure of network up
      and down-regulation dynamics may provide neuronal underpinnings for cognitive
      impairments seen in many mental disorders, such as, e.g., schizophrenia. We start
      by describing a common observation in functional imaging, the close overlap in
      fronto-parietal activations in healthy individuals to tasks that denote very
      different cognitive processes. We now suggest that this is because the brain
      utilizes the EMN network as a generalized response to tasks that exceeds a
      cognitive demand threshold and/or requires the processing of novel information.
      We further discuss how the EMN is related to the DMN, and how a network for
      extrinsic activity is related to a network for intrinsic activity. Finally, we
      discuss whether the EMN and DMN networks interact in a common single brain
      system, rather than being two separate and independent brain systems. 

PMID- 26300758
TI  - Frontal and occipital-parietal alpha oscillations distinguish between stimulus
      conflict and response conflict.
AB  - Conflicts between target and distraction can occur at the level of both stimulus
      and response processing. However, the neural oscillations underlying occurrence
      of the interference in different levels have not been understood well. Here, we
      reveal such a neural oscillation modulation by combining a 4:2 mapping design
      (two targets are mapped into one response key) with a practice paradigm (pretest,
      practice, and posttest) when healthy human participants were performing a novel
      color-word flanker task. Response time (RT) results revealed constant stimulus
      conflict (SC, stimulus incongruent minus congruent, SI-CO) but increased response
      conflict (RC, response incongruent minus stimulus incongruent, RI-SI) with
      practice. Event-related potential (ERP) results demonstrated stable P3 amplitude
      differences for the SI-CO in the centro-parietal region across practice, which
      may reflect maintenance of the stimulus processing; and significantly larger P3
      amplitudes in the same region for the RI relative to SI trial type in posttest,
      which may reflect inhibition of the distraction response. Further, neural
      oscillatory results showed that with practice, the lower alpha band in the
      frontal region and the upper alpha band in the occipital-parietal region
      distinguished between stimulus- and response-conflicts, respectively, suggesting
      that practice reduces the alertness (sensitiveness) of the brain to conflict
      occurrence, and enhances stimulus-response associations. 

PMID- 26300759
TI  - Pupil diameter reflects uncertainty in attentional selection during visual
      search.
AB  - Pupil diameter has long been used as a metric of cognitive processing. However,
      recent advances suggest that the cognitive sources of change in pupil size may
      reflect LC-NE function and the calculation of unexpected uncertainty in decision
      processes (Aston-Jones and Cohen, 2005; Yu and Dayan, 2005). In the current
      experiments, we explored the role of uncertainty in attentional selection on task
      evoked changes in pupil diameter during visual search. We found that task-evoked
      changes in pupil diameter were related to uncertainty during attentional
      selection as measured by reaction time (RT) and performance accuracy (Experiments
      1-2). Control analyses demonstrated that the results are unlikely to be due to
      error monitoring or response uncertainty. Our results suggest that pupil diameter
      can be used as an implicit metric of uncertainty in ongoing attentional selection
      requiring effortful control processes. 

PMID- 26300760
TI  - The steady-state response of the cerebral cortex to the beat of music reflects
      both the comprehension of music and attention.
AB  - The brain's analyses of speech and music share a range of neural resources and
      mechanisms. Music displays a temporal structure of complexity similar to that of
      speech, unfolds over comparable timescales, and elicits cognitive demands in
      tasks involving comprehension and attention. During speech processing,
      synchronized neural activity of the cerebral cortex in the delta and theta
      frequency bands tracks the envelope of a speech signal, and this neural activity
      is modulated by high-level cortical functions such as speech comprehension and
      attention. It remains unclear, however, whether the cortex also responds to the
      natural rhythmic structure of music and how the response, if present, is
      influenced by higher cognitive processes. Here we employ electroencephalography
      to show that the cortex responds to the beat of music and that this steady-state
      response reflects musical comprehension and attention. We show that the cortical
      response to the beat is weaker when subjects listen to a familiar tune than when
      they listen to an unfamiliar, non-sensical musical piece. Furthermore, we show
      that in a task of intermodal attention there is a larger neural response at the
      beat frequency when subjects attend to a musical stimulus than when they ignore
      the auditory signal and instead focus on a visual one. Our findings may be
      applied in clinical assessments of auditory processing and music cognition as
      well as in the construction of auditory brain-machine interfaces. 

PMID- 26300761
TI  - Muscle co-activity tuning in Parkinsonian hand movement: disease-specific changes
      at behavioral and cerebral level.
AB  - We investigated simple directional hand movements based on different degrees of
      muscle co-activity, at behavioral and cerebral level in healthy subjects and
      Parkinson's disease (PD) patients. We compared "singular" movements, dominated by
      the activity of one agonist muscle, to "composite" movements, requiring conjoint
      activity of multiple muscles, in a center-out (right hand) step-tracking task.
      Behavioral parameters were obtained by EMG and kinematic recordings. fMRI was
      used to investigate differences in underlying brain activations between PD
      patients (N = 12) and healthy (age-matched) subjects (N = 18). In healthy
      subjects, composite movements recruited the striatum and cortical areas
      comprising bilaterally the supplementary motor area and premotor cortex,
      contralateral medial prefrontal cortex, primary motor cortex, primary visual
      cortex, and ipsilateral superior parietal cortex. Contrarily, the ipsilateral
      cerebellum was more involved in singular movements. This striking dichotomy
      between striatal and cortical recruitment vs. cerebellar involvement was
      considered to reflect the complementary roles of these areas in motor control, in
      which the basal ganglia are involved in movement selection and the cerebellum in
      movement optimization. Compared to healthy subjects, PD patients showed decreased
      activation of the striatum and cortical areas in composite movement, while
      performing worse at behavioral level. This implies that PD patients are
      especially impaired on tasks requiring highly tuned muscle co-activity. Singular
      movement, on the other hand, was characterized by a combination of increased
      activation of the ipsilateral parietal cortex and left cerebellum. As singular
      movement performance was only slightly compromised, we interpret this as a
      reflection of increased visuospatial processing, possibly as a compensational
      mechanism. 

PMID- 26300762
TI  - Crossing boundaries: toward a general model of neuroaesthetics.

PMID- 26300763
TI  - Commentary: What visual illusions tell us about underlying neural mechanisms and
      observer strategies for tackling the inverse problem of achromatic perception.

PMID- 26300764
TI  - A kinematic study on (un)intentional imitation in bottlenose dolphins.
AB  - The aim of the present study was to investigate the effect of observing other's
      movements on subsequent performance in bottlenose dolphins. The imitative ability
      of non-human animals has intrigued a number of researchers. So far, however,
      studies in dolphins have been confined to intentional imitation concerned with
      the explicit request to imitate other agents. In the absence of instruction to
      imitate, do dolphins (un)intentionally replicate other's movement features? To
      test this, dolphins were filmed while reaching and touching a stimulus before and
      after observing another dolphin (i.e., model) performing the same action. All
      videos were reviewed and segmented in order to extract the relevant movements. A
      marker was inserted post hoc via software on the videos upon the anatomical
      landmark of interest (i.e., rostrum) and was tracked throughout the time course
      of the movement sequence. The movement was analyzed using an in-house software
      developed to perform two-dimensional (2D) post hoc kinematic analysis. The
      results indicate that dolphins' kinematics is sensitive to other's movement
      features. Movements performed for the "visuomotor priming" condition were
      characterized by a kinematic pattern similar to that performed by the observed
      dolphin (i.e., model). Addressing the issue of spontaneous imitation in
      bottlenose dolphins might allow ascertaining whether the potential or impulse to
      produce an imitative action is generated, not just when they intend to imitate,
      but whenever they watch another conspecific's behavior. In closing, this will
      clarify whether motor representational capacity is a by-product of factors
      specific to humans or whether more general characteristics such as processes of
      associative learning prompted by high level of encephalization could help to
      explain the evolution of this ability. 

PMID- 26300765
TI  - Synchronization-based computation through networks of coupled oscillators.
AB  - The mesoscopic activity of the brain is strongly dynamical, while at the same
      time exhibits remarkable computational capabilities. In order to examine how
      these two features coexist, here we show that the patterns of synchronized
      oscillations displayed by networks of neural mass models, representing cortical
      columns, can be used as substrates for Boolean-like computations. Our results
      reveal that the same neural mass network may process different combinations of
      dynamical inputs as different logical operations or combinations of them. This
      dynamical feature of the network allows it to process complex inputs in a very
      sophisticated manner. The results are reproduced experimentally with electronic
      circuits of coupled Chua oscillators, showing the robustness of this kind of
      computation to the intrinsic noise and parameter mismatch of the coupled
      oscillators. We also show that the information-processing capabilities of coupled
      oscillations go beyond the simple juxtaposition of logic gates. 

PMID- 26300766
TI  - Computational modeling of the neural representation of object shape in the
      primate ventral visual system.
AB  - Neurons in successive stages of the primate ventral visual pathway encode the
      spatial structure of visual objects. In this paper, we investigate through
      computer simulation how these cell firing properties may develop through
      unsupervised visually-guided learning. Individual neurons in the model are shown
      to exploit statistical regularity and temporal continuity of the visual inputs
      during training to learn firing properties that are similar to neurons in V4 and
      TEO. Neurons in V4 encode the conformation of boundary contour elements at a
      particular position within an object regardless of the location of the object on
      the retina, while neurons in TEO integrate information from multiple boundary
      contour elements. This representation goes beyond mere object recognition, in
      which neurons simply respond to the presence of a whole object, but provides an
      essential foundation from which the brain is subsequently able to recognize the
      whole object. 

PMID- 26300767
TI  - A neuronal network model for context-dependence of pitch change perception.
AB  - Many natural stimuli have perceptual ambiguities that can be cognitively resolved
      by the surrounding context. In audition, preceding context can bias the
      perception of speech and non-speech stimuli. Here, we develop a neuronal network
      model that can account for how context affects the perception of pitch change
      between a pair of successive complex tones. We focus especially on an ambiguous
      comparison-listeners experience opposite percepts (either ascending or
      descending) for an ambiguous tone pair depending on the spectral location of
      preceding context tones. We developed a recurrent, firing-rate network model,
      which detects frequency-change-direction of successively played stimuli and
      successfully accounts for the context-dependent perception demonstrated in
      behavioral experiments. The model consists of two tonotopically organized,
      excitatory populations, E up and E down, that respond preferentially to ascending
      or descending stimuli in pitch, respectively. These preferences are generated by
      an inhibitory population that provides inhibition asymmetric in frequency to the
      two populations; context dependence arises from slow facilitation of inhibition.
      We show that contextual influence depends on the spectral distribution of
      preceding tones and the tuning width of inhibitory neurons. Further, we
      demonstrate, using phase-space analysis, how the facilitated inhibition from
      previous stimuli and the waning inhibition from the just-preceding tone shape the
      competition between the E up and E down populations. In sum, our model accounts
      for contextual influences on the pitch change perception of an ambiguous tone
      pair by introducing a novel decoding strategy based on direction-selective units.
      The model's network architecture and slow facilitating inhibition emerge as
      predictions of neuronal mechanisms for these perceptual dynamics. Since the model
      structure does not depend on the specific stimuli, we show that it generalizes to
      other contextual effects and stimulus types. 

PMID- 26300768
TI  - The lateral reticular nucleus; integration of descending and ascending systems
      regulating voluntary forelimb movements.
AB  - Cerebellar control of movements is dependent on mossy fiber input conveying
      information about sensory and premotor activity in the spinal cord. While much is
      known about spino-cerebellar systems, which provide the cerebellum with detailed
      sensory information, much less is known about systems conveying motor
      information. Individual motoneurones do not have projections to spino-cerebellar
      neurons. Instead, the fastest route is from last order spinal interneurons. In
      order to identify the networks that convey ascending premotor information from
      last order interneurons, we have focused on the lateral reticular nucleus (LRN),
      which provides the major mossy fiber input to cerebellum from spinal
      interneuronal systems. Three spinal ascending systems to the LRN have been
      investigated: the C3-C4 propriospinal neurones (PNs), the ipsilateral forelimb
      tract (iFT) and the bilateral ventral flexor reflex tract (bVFRT). Voluntary
      forelimb movements involve reaching and grasping together with necessary postural
      adjustments and each of these three interneuronal systems likely contribute to
      specific aspects of forelimb motor control. It has been demonstrated that the
      command for reaching can be mediated via C3-C4 PNs, while the command for
      grasping is conveyed via segmental interneurons in the forelimb segments. Our
      results reveal convergence of ascending projections from all three interneuronal
      systems in the LRN, producing distinct combinations of excitation and inhibition.
      We have also identified a separate descending control of LRN neurons exerted via
      a subgroup of cortico-reticular neurones. The LRN projections to the deep
      cerebellar nuclei exert a direct excitatory effect on descending motor pathways
      via the reticulospinal, vestibulospinal, and other supraspinal tracts, and might
      play a key role in cerebellar motor control. Our results support the hypothesis
      that the LRN provides the cerebellum with highly integrated information, enabling
      cerebellar control of complex forelimb movements. 

PMID- 26300769
TI  - Learning structure of sensory inputs with synaptic plasticity leads to
      interference.
AB  - Synaptic plasticity is often explored as a form of unsupervised adaptation in
      cortical microcircuits to learn the structure of complex sensory inputs and
      thereby improve performance of classification and prediction. The question of
      whether the specific structure of the input patterns is encoded in the structure
      of neural networks has been largely neglected. Existing studies that have
      analyzed input-specific structural adaptation have used simplified, synthetic
      inputs in contrast to complex and noisy patterns found in real-world sensory
      data. In this work, input-specific structural changes are analyzed for three
      empirically derived models of plasticity applied to three temporal sensory
      classification tasks that include complex, real-world visual and auditory data.
      Two forms of spike-timing dependent plasticity (STDP) and the Bienenstock-Cooper
      Munro (BCM) plasticity rule are used to adapt the recurrent network structure
      during the training process before performance is tested on the pattern
      recognition tasks. It is shown that synaptic adaptation is highly sensitive to
      specific classes of input pattern. However, plasticity does not improve the
      performance on sensory pattern recognition tasks, partly due to synaptic
      interference between consecutively presented input samples. The changes in
      synaptic strength produced by one stimulus are reversed by the presentation of
      another, thus largely preventing input-specific synaptic changes from being
      retained in the structure of the network. To solve the problem of interference,
      we suggest that models of plasticity be extended to restrict neural activity and
      synaptic modification to a subset of the neural circuit, which is increasingly
      found to be the case in experimental neuroscience. 

PMID- 26300770
TI  - The neural mechanisms underlying the aging-related enhancement of positive
      affects: electrophysiological evidences.
AB  - BACKGROUND: Previous studies reported that old adults, relative to young adults,
      showed improvement of emotional stability and increased experiences of positive
      affects. METHODS: In order to better understand the neural underpinnings behind
      the aging-related enhancement of positive affects, it is necessary to investigate
      whether old and young adults differ in the threshold of eliciting positive or
      negative emotional reactions. However, no studies have examined emotional
      reaction differences between old and young adults by manipulating the intensity
      of emotional stimuli to date. To clarify this issue, the present study examined
      the impact of aging on the brain's susceptibility to affective pictures of
      varying emotional intensities. We recorded event-related potentials (ERP) for
      highly negative (HN), mildly negative (MN) and neutral pictures in the negative
      experimental block; and for highly positive (HP), mildly positive (MP) and
      neutral pictures in the positive experimental block, when young and old adults
      were required to count the number of pictures, irrespective of the emotionality
      of the pictures. RESULTS: Event-related potentials results showed that LPP (late
      positive potentials) amplitudes were larger for HN and MN stimuli compared to
      neutral stimuli in young adults, but not in old adults. By contrast, old adults
      displayed larger LPP amplitudes for HP and MP relative to neutral stimuli, while
      these effects were absent for young adults. In addition, old adults reported more
      frequent perception of positive stimuli and less frequent perception of negative
      stimuli than young adults. The post-experiment stimulus assessment showed more
      positive ratings of Neutral and MP stimuli, and reduced arousal ratings of HN
      stimuli in old compared to young adults. CONCLUSION: These results suggest that
      old adults are more resistant to the impact of negative stimuli, while they are
      equipped with enhanced attentional bias for positive stimuli. The implications of
      these results to the aging-related enhancement of positive affects were
      discussed.

PMID- 26300771
TI  - Differences in prefrontal cortex activation and deactivation during strategic
      episodic verbal memory encoding in mild cognitive impairment.
AB  - In this study we examined differences in fMRI activation and deactivation
      patterns during episodic verbal memory encoding between individuals with MCI (n =
      18) and healthy controls (HCs) (n = 17). Participants were scanned in two
      different sessions during the application of self-initiated or directed
      instructions to apply semantic strategies at encoding of word lists. MCI
      participants showed reduced free recall scores when using self-initiated encoding
      strategies that were increased to baseline controls' level after directed
      instructions were provided. During directed strategic encoding, greater
      recruitment of frontoparietal regions was observed in both MCI and control
      groups; group differences between sessions were observed in the ventromedial
      prefrontal cortex and the right superior frontal gyrus. This study provides
      evidence suggesting that differences of activity in these regions may be related
      to encoding deficits in MCI, possibly mediating executive functions during task
      performance. 

PMID- 26300772
TI  - Gains in cognition through combined cognitive and physical training: the role of
      training dosage and severity of neurocognitive disorder.
AB  - Physical as well as cognitive training interventions improve specific cognitive
      functions but effects barely generalize on global cognition. Combined physical
      and cognitive training may overcome this shortcoming as physical training may
      facilitate the neuroplastic potential which, in turn, may be guided by cognitive
      training. This study aimed at investigating the benefits of combined training on
      global cognition while assessing the effect of training dosage and exploring the
      role of several potential effect modifiers. In this multi-center study, 322 older
      adults with or without neurocognitive disorders (NCDs) were allocated to a
      computerized, game-based, combined physical and cognitive training group (n =
      237) or a passive control group (n = 85). Training group participants were
      allocated to different training dosages ranging from 24 to 110 potential
      sessions. In a pre-post-test design, global cognition was assessed by averaging
      standardized performance in working memory, episodic memory and executive
      function tests. The intervention group increased in global cognition compared to
      the control group, p = 0.002, Cohen's d = 0.31. Exploratory analysis revealed a
      trend for less benefits in participants with more severe NCD, p = 0.08
      (cognitively healthy: d = 0.54; mild cognitive impairment: d = 0.19; dementia: d
      = 0.04). In participants without dementia, we found a dose-response effect of the
      potential number and of the completed number of training sessions on global
      cognition, p = 0.008 and p = 0.04, respectively. The results indicate that
      combined physical and cognitive training improves global cognition in a dose
      responsive manner but these benefits may be less pronounced in older adults with
      more severe NCD. The long-lasting impact of combined training on the incidence
      and trajectory of NCDs in relation to its severity should be assessed in future
      long-term trials. 

PMID- 26300774
TI  - Complementary and synergistic therapeutic effects of compounds found in Kampo
      medicine: analysis of daikenchuto.
AB  - Herbal medicines have been used in Japan for more than 1500 years and traditional
      Japanese medicines (Kampo medicines) are now fully integrated into the modern
      healthcare system. In total, 148 Kampo formulae are officially approved as
      prescription drugs and covered by the national health insurance system in Japan.
      However, despite their long track record of clinical use, the multi-targeted,
      multi-component properties of Kampo medicines, which are fundamentally different
      from Western medicines, have made it difficult to create a suitable framework for
      conducting well-designed, large-scale clinical trials. In turn, this has led to
      misconceptions among western trained physicians concerning the paucity of
      scientific evidence for the beneficial effects of Kampo medicines. Fortunately,
      there has been a recent surge in scientifically robust data from basic and
      clinical studies for some of the Kampo medicines, e.g., daikenchuto (TU-100).
      Numerous basic and clinical studies on TU-100, including placebo-controlled
      double-blind studies for various gastrointestinal disorders, and absorption,
      distribution, metabolism and excretion (ADME) studies, have been conducted or are
      in the process of being conducted in both Japan and the USA. Clinical studies
      suggest that TU-100 is beneficial for postoperative complications, especially
      ileus and abdominal bloating. ADME and basic studies indicate that the effect of
      TU-100 is a composite of numerous actions mediated by multiple compounds supplied
      via multiple routes. In addition to known mechanisms of action via
      enteric/sensory nerve stimulation, novel mechanisms via the TRPA1 channel and two
      pore domain potassium channels have recently been elucidated. TU-100 compounds
      target these channels with and without absorption, both before and after
      metabolic activation by enteric flora, with different timings and possibly with
      synergism. 

PMID- 26300773
TI  - The translational aspect of complementary and alternative medicine for cancer
      with particular emphasis on Kampo.
AB  - Complementary and alternative medicine (CAM) including Japanese Kampo is known to
      have anticancer potential. An increasing number of cancer survivors are using CAM
      for disease prevention, immune system enhancement, and symptom control. Although
      there have been abundant previous clinical reports regarding CAM, scientific
      investigations aimed at acquiring quantifiable results in clinical trials, as
      well as basic research regarding CAM, have only recently been undertaken. Recent
      studies suggest that CAM enhancement of immune function is related to cytokines.
      This review provides a translational aspect of CAM, particularly Hozai in Kampo
      from both scientific and clinical points of view for further development of CAM
      for cancer treatment. 

PMID- 26300775
TI  - Global and local missions of cAMP signaling in neural plasticity, learning, and
      memory.
AB  - The fruit fly Drosophila melanogaster has been a popular model to study cAMP
      signaling and resultant behaviors due to its powerful genetic approaches. All
      molecular components (AC, PDE, PKA, CREB, etc) essential for cAMP signaling have
      been identified in the fly. Among them, adenylyl cyclase (AC) gene rutabaga and
      phosphodiesterase (PDE) gene dunce have been intensively studied to understand
      the role of cAMP signaling. Interestingly, these two mutant genes were originally
      identified on the basis of associative learning deficits. This commentary
      summarizes findings on the role of cAMP in Drosophila neuronal excitability,
      synaptic plasticity and memory. It mainly focuses on two distinct mechanisms
      (global versus local) regulating excitatory and inhibitory synaptic plasticity
      related to cAMP homeostasis. This dual regulatory role of cAMP is to increase the
      strength of excitatory neural circuits on one hand, but to act locally on
      postsynaptic GABA receptors to decrease inhibitory synaptic plasticity on the
      other. Thus the action of cAMP could result in a global increase in the neural
      circuit excitability and memory. Implications of this cAMP signaling related to
      drug discovery for neural diseases are also described. 

PMID- 26300777
TI  - Corrigendum: Ferritin polarization and iron transport across monolayer epithelial
      barriers in mammals.
AB  - [This corrects the article on p. 194 in vol. 5, PMID: 25202274.]. 

PMID- 26300776
TI  - The role of the serotonin receptor subtypes 5-HT1A and 5-HT7 and its interaction
      in emotional learning and memory.
AB  - Serotonin [5-hydroxytryptamine (5-HT)] is a multifunctional neurotransmitter
      innervating cortical and limbic areas involved in cognition and emotional
      regulation. Dysregulation of serotonergic transmission is associated with
      emotional and cognitive deficits in psychiatric patients and animal models. Drugs
      targeting the 5-HT system are widely used to treat mood disorders and anxiety
      like behaviors. Among the fourteen 5-HT receptor (5-HTR) subtypes, the 5-HT1AR
      and 5-HT7R are associated with the development of anxiety, depression and
      cognitive function linked to mechanisms of emotional learning and memory. In
      rodents fear conditioning and passive avoidance (PA) are associative learning
      paradigms to study emotional memory. This review assesses the role of 5-HT1AR and
      5-HT7R as well as their interplay at the molecular, neurochemical and behavioral
      level. Activation of postsynaptic 5-HT1ARs impairs emotional memory through
      attenuation of neuronal activity, whereas presynaptic 5-HT1AR activation reduces
      5-HT release and exerts pro-cognitive effects on PA retention. Antagonism of the
      5-HT1AR facilitates memory retention possibly via 5-HT7R activation and evidence
      is provided that 5HT7R can facilitate emotional memory upon reduced 5-HT1AR
      transmission. These findings highlight the differential role of these 5-HTRs in
      cognitive/emotional domains of behavior. Moreover, the results indicate that
      tonic and phasic 5-HT release can exert different and potentially opposing
      effects on emotional memory, depending on the states of 5-HT1ARs and 5-HT7Rs and
      their interaction. Consequently, individual differences due to genetic and/or
      epigenetic mechanisms play an essential role for the responsiveness to drug
      treatment, e.g., by SSRIs which increase intrasynaptic 5-HT levels thereby
      activating multiple pre- and postsynaptic 5-HTR subtypes. 

PMID- 26300778
TI  - The genetically encoded tool set for investigating cAMP: more than the sum of its
      parts.
AB  - Intracellular fluctuations of the second messenger cyclic AMP (cAMP) are
      regulated with spatial and temporal precision. This regulation is supported by
      the sophisticated arrangement of cyclases, phosphodiesterases, anchoring
      proteins, and receptors for cAMP. Discovery of these nuances to cAMP signaling
      has been facilitated by the development of genetically encodable tools for
      monitoring and manipulating cAMP and the proteins that support cAMP signaling. In
      this review, we discuss the state-of-the-art in development of different
      genetically encoded tools for sensing cAMP and the activity of its primary
      intracellular receptor protein kinase A (PKA). We introduce sequences for
      encoding adenylyl cyclases that enable cAMP levels to be artificially elevated
      within cells. We chart the evolution of sequences for selectively modifying
      protein-protein interactions that support cAMP signaling, and for driving cAMP
      sensors and manipulators to different subcellular locations. Importantly, these
      different genetically encoded tools can be applied synergistically, and we
      highlight notable instances that take advantage of this property. Finally, we
      consider prospects for extending the utility of the tool set to support further
      insights into the role of cAMP in health and disease. 

PMID- 26300779
TI  - Manufacturing of dental pulp cell-based products from human third molars: current
      strategies and future investigations.
AB  - In recent years, mesenchymal cell-based products have been developed to improve
      surgical therapies aimed at repairing human tissues. In this context, the tooth
      has recently emerged as a valuable source of stem/progenitor cells for
      regenerating orofacial tissues, with easy access to pulp tissue and high
      differentiation potential of dental pulp mesenchymal cells. International
      guidelines now recommend the use of standardized procedures for cell isolation,
      storage and expansion in culture to ensure optimal reproducibility, efficacy and
      safety when cells are used for clinical application. However, most dental pulp
      cell-based medicinal products manufacturing procedures may not be fully
      satisfactory since they could alter the cells biological properties and the
      quality of derived products. Cell isolation, enrichment and cryopreservation
      procedures combined to long-term expansion in culture media containing xeno- and
      allogeneic components are known to affect cell phenotype, viability,
      proliferation and differentiation capacities. This article focuses on current
      manufacturing strategies of dental pulp cell-based medicinal products and
      proposes a new protocol to improve efficiency, reproducibility and safety of
      these strategies. 

PMID- 26300780
TI  - Toward the modeling of mucus draining from human lung: role of airways
      deformation on air-mucus interaction.
AB  - Chest physiotherapy is an empirical technique used to help secretions to get out
      of the lung whenever stagnation occurs. Although commonly used, little is known
      about the inner mechanisms of chest physiotherapy and controversies about its use
      are coming out regularly. Thus, a scientific validation of chest physiotherapy is
      needed to evaluate its effects on secretions. We setup a quasi-static numerical
      model of chest physiotherapy based on thorax and lung physiology and on their
      respective biophysics. We modeled the lung with an idealized deformable symmetric
      bifurcating tree. Bronchi and their inner fluids mechanics are assumed
      axisymmetric. Static data from the literature is used to build a model for the
      lung's mechanics. Secretions motion is the consequence of the shear constraints
      apply by the air flow. The input of the model is the pressure on the chest wall
      at each time, and the output is the bronchi geometry and air and secretions
      properties. In the limit of our model, we mimicked manual and mechanical chest
      physiotherapy techniques. We show that for secretions to move, air flow has to be
      high enough to overcome secretion resistance to motion. Moreover, the higher the
      pressure or the quicker it is applied, the higher is the air flow and thus the
      mobilization of secretions. However, pressures too high are efficient up to a
      point where airways compressions prevents air flow to increase any further.
      Generally, the first effects of manipulations is a decrease of the airway tree
      hydrodynamic resistance, thus improving ventilation even if secretions do not get
      out of the lungs. Also, some secretions might be pushed deeper into the lungs;
      this effect is stronger for high pressures and for mechanical chest
      physiotherapy. Finally, we propose and tested two a dimensional numbers that
      depend on lung properties and that allow to measure the efficiency and comfort of
      a manipulation. 

PMID- 26300781
TI  - Muscular coordination of biceps brachii and brachioradialis in elbow flexion with
      respect to hand position.
AB  - Contribution of synergistic muscles toward specific movements over multi joint
      systems may change with varying position of distal or proximal joints. Purpose of
      this study is to reveal the relationship of muscular coordination of
      brachioradialis and biceps brachii during elbow flexion with respect to hand
      position and biomechanical advantages and disadvantages of biceps brachii. A
      group of 16 healthy subjects has been advised to perform 20 repetitions of single
      elbow flexion movements in different hand positions (pronated, neutral, and
      supinated). With a speed of 20 degrees /s, simultaneously sEMG of biceps brachii
      and brachioradialis and kinematics of the movement were recorded in a motion
      analysis laboratory. Normalized to MVC the sEMG amplitudes of both muscles
      contributing to elbow flexion movements were compared in pronated, supinated, and
      neutral hand position over elbow joint angle. Significant differences in the
      contribution of brachioradialis were found in pronated hand position compared to
      supinated and neutral hand position while the muscular activity of biceps brachii
      shows no significant changes in any hand position. In conclusion, a statistical
      significant dependency of the inter-muscular coordination between biceps brachii
      and brachioradialis during elbow flexion with respect to hand position has been
      observed depending on a biomechanical disadvantage of biceps brachii. 

PMID- 26300782
TI  - Xylooligosaccharide supplementation alters gut bacteria in both healthy and
      prediabetic adults: a pilot study.
AB  - BACKGROUND: It has been suggested that gut microbiota is altered in Type 2
      Diabetes Mellitus (T2DM) patients. OBJECTIVE: This study was to evaluate the
      effect of the prebiotic xylooligosaccharide (XOS) on the gut microbiota in both
      healthy and prediabetic (Pre-DM) subjects, as well as impaired glucose tolerance
      (IGT) in Pre-DM. SUBJECTS/METHODS: Pre-DM (n = 13) or healthy (n = 16) subjects
      were randomized to receive 2 g/day XOS or placebo for 8-weeks. In Pre-DM
      subjects, body composition and oral glucose tolerance test (OGTT) was done at
      baseline and week 8. Stool from Pre-DM and healthy subjects at baseline and week
      8 was analyzed for gut microbiota characterization using Illumina MiSeq
      sequencing. RESULTS: We identified 40 Pre-DM associated bacterial taxa. Among
      them, the abundance of the genera Enterorhabdus, Howardella, and Slackia was
      higher in Pre-DM. XOS significantly decreased or reversed the increase in
      abundance of Howardella, Enterorhabdus, and Slackia observed in healthy or Pre-DM
      subjects. Abundance of the species Blautia hydrogenotrophica was lower in pre-DM
      subjects, while XOS increased its abundance. In Pre-DM, XOS showed a tendency to
      reduce OGTT 2-h insulin levels (P = 0.13), but had no effect on body composition,
      HOMA-IR, serum glucose, triglyceride, satiety hormones, and TNFalpha. CONCLUSION:
      This is the first clinical observation of modifications of the gut microbiota by
      XOS in both healthy and Pre-DM subjects in a pilot study. Prebiotic XOS may be
      beneficial in reversing changes in the gut microbiota during the development of
      diabetes. CLINICAL TRIAL REGISTRATION: NCT01944904
      (https://clinicaltrials.gov/ct2/show/NCT01944904).

PMID- 26300783
TI  - High-order finite element methods for cardiac monodomain simulations.
AB  - Computational modeling of tissue-scale cardiac electrophysiology requires
      numerically converged solutions to avoid spurious artifacts. The steep gradients
      inherent to cardiac action potential propagation necessitate fine spatial scales
      and therefore a substantial computational burden. The use of high-order
      interpolation methods has previously been proposed for these simulations due to
      their theoretical convergence advantage. In this study, we compare the
      convergence behavior of linear Lagrange, cubic Hermite, and the newly proposed
      cubic Hermite-style serendipity interpolation methods for finite element
      simulations of the cardiac monodomain equation. The high-order methods reach
      converged solutions with fewer degrees of freedom and longer element edge lengths
      than traditional linear elements. Additionally, we propose a dimensionless
      number, the cell Thiele modulus, as a more useful metric for determining solution
      convergence than element size alone. Finally, we use the cell Thiele modulus to
      examine convergence criteria for obtaining clinically useful activation patterns
      for applications such as patient-specific modeling where the total activation
      time is known a priori. 

PMID- 26300784
TI  - Direct conscious telemetry recordings demonstrate increased renal sympathetic
      nerve activity in rats with chronic kidney disease.
AB  - Chronic kidney disease (CKD) is associated with sympathetic hyperactivity and
      impaired blood pressure control reflex responses, yet direct evidence
      demonstrating these features of autonomic dysfunction in conscious animals is
      still lacking. Here we measured renal sympathetic nerve activity (RSNA) and mean
      arterial pressure (MAP) using telemetry-based recordings in a rat model of CKD,
      the Lewis Polycystic Kidney (LPK) rat, and assessed responses to chemoreflex
      activation and acute stress. Male LPK and Lewis control animals (total n = 16)
      were instrumented for telemetric recording of RSNA and MAP. At 12-13 weeks-of
      age, resting RSNA and MAP, sympathetic and haemodynamic responses to both
      peripheral (hypoxia: 10% O2) and central chemoreflex (hypercapnia: 7% CO2)
      activation and acute stress (open-field exposure), were measured. As indicators
      of renal function, urinary protein (UPro) and creatinine (UCr) levels were
      assessed. LPK rats had higher resting RSNA (1.2 +/- 0.1 vs. 0.6 +/- 0.1 MUV, p <
      0.05) and MAP (151 +/- 8 vs. 97 +/- 2 mmHg, p < 0.05) compared to Lewis. MAP was
      negatively correlated with UCr (r = -0.80, p = 0.002) and positively correlated
      with RSNA (r = 0.66, p = 0.014), with multiple linear regression modeling
      indicating the strongest correlation was with Ucr. RSNA and MAP responses to
      activation of the central chemoreflex and open-field stress were reduced in the
      LPK relative to the Lewis (all p < 0.05). This is the first description of dual
      conscious telemetry recording of RSNA and MAP in a genetic rodent model of CKD.
      Elevated RSNA is likely a key contributor to the marked hypertension in this
      model, while attenuated RSNA and MAP responses to central chemoreflex activation
      and acute stress in the LPK indicate possible deficits in the neural processing
      of autonomic outflows evoked by these sympathoexcitatory pathways. 

PMID- 26300786
TI  - Dentin phosphophoryn in the matrix activates AKT and mTOR signaling pathway to
      promote preodontoblast survival and differentiation.
AB  - Dentin phosphophoryn (DPP) is an extracellular matrix protein synthesized by
      odontoblasts. It is highly acidic and the phosphorylated protein possesses a
      strong affinity for calcium ions. Therefore, DPP in the extracellular matrix can
      promote hydroxyapatite nucleation and can regulate the size of the growing
      crystal. Besides its calcium binding property, DPP can initiate signaling
      functions from the ECM (Extracellular matrix). The signals that promote the
      cytodifferentiation of preodontoblasts to fully functional odontoblasts are not
      known. In this study, we demonstrate that preodontoblasts on a DPP matrix,
      generates mechanical and biochemical signals. This is initiated by the ligation
      of the integrins with the RGD containing DPP. The downstream biochemical response
      observed is the activation of the AKT(protein kinase B) and mTOR (mammalian
      target of rapamycin) signaling pathways leading to the activation of the
      transcription factor NF-kappaB (Nuclear factor kappaB). Terminal differentiation
      of the preodontoblasts was assessed by identifying phosphate and calcium deposits
      in the matrix using von Kossa and Alizarin red staining respectively. Identifying
      the signaling pathways initiated by DPP in the dentin matrix would help in
      devising strategies for dentin tissue engineering. 

PMID- 26300785
TI  - Accessory proteins for heterotrimeric G-proteins in the kidney.
AB  - Heterotrimeric G-proteins play a fundamentally important role in regulating
      signal transduction pathways in the kidney. Accessory proteins are being
      identified as direct binding partners for heterotrimeric G-protein alpha or
      betagamma subunits to promote more diverse mechanisms by which G-protein
      signaling is controlled. In some instances, accessory proteins can modulate the
      signaling magnitude, localization, and duration following the activation of cell
      membrane-associated receptors. Alternatively, accessory proteins complexed with
      their G-protein alpha or betagamma subunits can promote non-canonical models of
      signaling activity within the cell. In this review, we will highlight the
      expression profile, localization and functional importance of these newly
      identified accessory proteins to control the function of select G-protein
      subunits under normal and various disease conditions observed in the kidney. 

PMID- 26300787
TI  - In adenosine A2B knockouts acute treatment with inorganic nitrate improves
      glucose disposal, oxidative stress, and AMPK signaling in the liver.
AB  - RATIONALE: Accumulating studies suggest that nitric oxide (NO) deficiency and
      oxidative stress are central pathological mechanisms in type 2 diabetes (T2D).
      Recent findings demonstrate therapeutic effects by boosting the nitrate-nitrite
      NO pathway, which is an alternative pathway for NO formation. This study aimed at
      investigating the acute effects of inorganic nitrate on glucose and insulin
      signaling in adenosine A2B receptor knockout mice (A(-/-) 2B), a genetic mouse
      model of impaired metabolic regulation. METHODS: Acute effects of nitrate
      treatment were investigated in aged wild-type (WT) and A(-/-) 2B mice. One hour
      after injection with nitrate (0.1 mmol/kg, i.p.) or placebo, metabolic regulation
      was evaluated by intraperitoneal glucose and insulin tolerance tests. NADPH
      oxidase-mediated superoxide production and AMPK phosphorylation were measured in
      livers obtained from non-treated or glucose-treated mice, with or without prior
      nitrate injection. Plasma was used to determine insulin resistance (HOMA-IR) and
      NO signaling. RESULTS: A(-/-) 2B displayed increased body weight, reduced glucose
      clearance, and attenuated overall insulin responses compared with age-matched WT
      mice. Nitrate treatment increased circulating levels of nitrate, nitrite and cGMP
      in the A(-/-) 2B, and improved glucose clearance. In WT mice, however, nitrate
      treatment did not influence glucose clearance. HOMA-IR increased following
      glucose injection in the A(-/-) 2B, but remained at basal levels in mice
      pretreated with nitrate. NADPH oxidase activity in livers from A(-/-) 2B, but not
      WT mice, was reduced by nitrate treatment. Livers from A(-/-) 2B displayed
      reduced AMPK phosphorylation compared with WT mice, and this was increased by
      nitrate treatment. Finally, injection with the anti-diabetic agent metformin
      induced similar therapeutic effects in the A(-/-) 2B as observed with nitrate.
      CONCLUSION: The A(-/-) 2B mouse is a genetic mouse model of metabolic syndrome.
      Acute treatment with nitrate improved the metabolic profile in it, at least
      partly via reduction in oxidative stress and improved AMPK signaling in the
      liver.

PMID- 26300788
TI  - The renal nerves in chronic heart failure: efferent and afferent mechanisms.
AB  - The function of the renal nerves has been an area of scientific and medical
      interest for many years. The recent advent of a minimally invasive catheter-based
      method of renal denervation has renewed excitement in understanding the afferent
      and efferent actions of the renal nerves in multiple diseases. While hypertension
      has been the focus of much this work, less attention has been given to the role
      of the renal nerves in the development of chronic heart failure (CHF). Recent
      studies from our laboratory and those of others implicate an essential role for
      the renal nerves in the development and progression of CHF. Using a rabbit
      tachycardia model of CHF and surgical unilateral renal denervation, we provide
      evidence for both renal efferent and afferent mechanisms in the pathogenesis of
      CHF. Renal denervation prevented the decrease in renal blood flow observed in CHF
      while also preventing increases in Angiotensin-II receptor protein in the
      microvasculature of the renal cortex. Renal denervation in CHF also reduced
      physiological markers of autonomic dysfunction including an improvement in
      arterial baroreflex function, heart rate variability, and decreased resting
      cardiac sympathetic tone. Taken together, the renal sympathetic nerves are
      necessary in the pathogenesis of CHF via both efferent and afferent mechanisms.
      Additional investigation is warranted to fully understand the role of these
      nerves and their role as a therapeutic target in CHF. 

PMID- 26300789
TI  - Editorial: Cognition Across the Psychiatric Disorder Spectrum: From Mental Health
      to Clinical Diagnosis.

PMID- 26300790
TI  - Spreading Effect of tDCS in Individuals with Attention-Deficit/Hyperactivity
      Disorder as Shown by Functional Cortical Networks: A Randomized, Double-Blind,
      Sham-Controlled Trial.
AB  - BACKGROUND: Transcranial direct current stimulation (tDCS) is known to modulate
      spontaneous neural network excitability. The cognitive improvement observed in
      previous trials raises the potential of this technique as a possible therapeutic
      tool for use in attention-deficit/hyperactivity disorder (ADHD) population.
      However, to explore the potential of this technique as a treatment approach, the
      functional parameters of brain connectivity and the extent of its effects need to
      be more fully investigated. OBJECTIVE: The aim of this study was to investigate a
      functional cortical network (FCN) model based on electroencephalographic activity
      for studying the dynamic patterns of brain connectivity modulated by tDCS and the
      distribution of its effects in individuals with ADHD. METHODS: Sixty ADHD
      patients participated in a parallel, randomized, double-blind, sham-controlled
      trial. Individuals underwent a single session of sham or anodal tDCS at 1 mA of
      current intensity over the left dorsolateral prefrontal cortex for 20 min. The
      acute effects of stimulation on brain connectivity were assessed using the FCN
      model based on electroencephalography activity. RESULTS: Comparing the weighted
      node degree within groups prior to and following the intervention, a
      statistically significant difference was found in the electrodes located on the
      target and correlated areas in the active group (p < 0.05), while no
      statistically significant results were found in the sham group (p >= 0.05; paired
      sample Wilcoxon signed-rank test). CONCLUSION: Anodal tDCS increased functional
      brain connectivity in individuals with ADHD compared to data recorded in the
      baseline resting state. In addition, although some studies have suggested that
      the effects of tDCS are selective, the present findings show that its modulatory
      activity spreads. Further studies need to be performed to investigate the dynamic
      patterns and physiological mechanisms underlying the modulatory effects of tDCS.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT01968512.

PMID- 26300791
TI  - Toward an ecological analysis of Bayesian inferences: how task characteristics
      influence responses.
AB  - In research on Bayesian inferences, the specific tasks, with their narratives and
      characteristics, are typically seen as exchangeable vehicles that merely
      transport the structure of the problem to research participants. In the present
      paper, we explore whether, and possibly how, task characteristics that are
      usually ignored influence participants' responses in these tasks. We focus on
      both quantitative dimensions of the tasks, such as their base rates, hit rates,
      and false-alarm rates, as well as qualitative characteristics, such as whether
      the task involves a norm violation or not, whether the stakes are high or low,
      and whether the focus is on the individual case or on the numbers. Using a data
      set of 19 different tasks presented to 500 different participants who provided a
      total of 1,773 responses, we analyze these responses in two ways: first, on the
      level of the numerical estimates themselves, and second, on the level of various
      response strategies, Bayesian and non-Bayesian, that might have produced the
      estimates. We identified various contingencies, and most of the task
      characteristics had an influence on participants' responses. Typically, this
      influence has been stronger when the numerical information in the tasks was
      presented in terms of probabilities or percentages, compared to natural
      frequencies - and this effect cannot be fully explained by a higher proportion of
      Bayesian responses when natural frequencies were used. One characteristic that
      did not seem to influence participants' response strategy was the numerical value
      of the Bayesian solution itself. Our exploratory study is a first step toward an
      ecological analysis of Bayesian inferences, and highlights new avenues for future
      research. 

PMID- 26300792
TI  - Learning to perceive and recognize a second language: the L2LP model revised.
AB  - We present a test of a revised version of the Second Language Linguistic
      Perception (L2LP) model, a computational model of the acquisition of second
      language (L2) speech perception and recognition. The model draws on phonetic,
      phonological, and psycholinguistic constructs to explain a number of L2 learning
      scenarios. However, a recent computational implementation failed to validate a
      theoretical proposal for a learning scenario where the L2 has less phonemic
      categories than the native language (L1) along a given acoustic continuum.
      According to the L2LP, learners faced with this learning scenario must not only
      shift their old L1 phoneme boundaries but also reduce the number of categories
      employed in perception. Our proposed revision to L2LP successfully accounts for
      this updating in the number of perceptual categories as a process driven by the
      meaning of lexical items, rather than by the learners' awareness of the number
      and type of phonemes that are relevant in their new language, as the previous
      version of L2LP assumed. Results of our simulations show that meaning-driven
      learning correctly predicts the developmental path of L2 phoneme perception seen
      in empirical studies. Additionally, and to contribute to a long-standing debate
      in psycholinguistics, we test two versions of the model, with the stages of
      phonemic perception and lexical recognition being either sequential or
      interactive. Both versions succeed in learning to recognize minimal pairs in the
      new L2, but make diverging predictions on learners' resulting phonological
      representations. In sum, the proposed revision to the L2LP model contributes to
      our understanding of L2 acquisition, with implications for speech processing in
      general. 

PMID- 26300793
TI  - Coexistence and different determinants of posttraumatic stress disorder and
      posttraumatic growth among Chinese survivors after earthquake: role of resilience
      and rumination.
AB  - Posttraumatic stress disorder (PTSD) and posttraumatic growth (PTG) are two
      different outcomes that may occur after experiencing traumatic events. Resilience
      and rumination are two important factors that determine the development of these
      outcomes after trauma. We investigated the association between these two factors,
      PTSD and PTG, among Chinese survivors in an earthquake. With a convenience sample
      of 318 survivors from earthquake, we measured trauma exposure, PTSD, PTG,
      resilience, and rumination (Impact of Event Scale-Revised, Posttraumatic Growth
      Inventory, 10 item Connor-Davidson Resilience Scale, Ruminative Response Scale).
      Then we used bivariate correlation and structural equation modeling to examine
      the structure of relations among these factors. Results showed that resilience
      and reflective rumination have a positive effect on PTG (beta = 0.32, p < 0.001;
      beta = 0.17, p = 0.049). Earthquake exposure, brooding rumination and depressed
      related rumination are related with higher level of PTSD (beta = 0.10, p = 0.021;
      beta = 0.33, p < 0.001; beta = 0.36, p < 0.001). The findings suggest distinct
      determinants of the negative and positive outcomes, and this may provide better
      understanding about the risk and protective factors for traumatic reactions. 

PMID- 26300794
TI  - Problem solving stages in the five square problem.
AB  - According to the restructuring hypothesis, insight problem solving typically
      progresses through consecutive stages of search, impasse, insight, and search
      again for someone, who solves the task. The order of these stages was determined
      through self-reports of problem solvers and has never been verified behaviorally.
      We asked whether individual analysis of problem solving attempts of participants
      revealed the same order of problem solving stages as defined by the theory and
      whether their subjective feelings corresponded to the problem solving stages they
      were in. Our participants tried to solve the Five-Square problem in an online
      task, while we recorded the time and trajectory of their stick movements. After
      the task they were asked about their feelings related to insight and some of them
      also had the possibility of reporting impasse while working on the task. We found
      that the majority of participants did not follow the classic four-stage model of
      insight, but had more complex sequences of problem solving stages, with search
      and impasse recurring several times. This means that the classic four-stage model
      is not sufficient to describe variability on the individual level. We revised the
      classic model and we provide a new model that can generate all sequences found.
      Solvers reported insight more often than non-solvers and non-solvers reported
      impasse more often than solvers, as expected; but participants did not report
      impasse more often during behaviorally defined impasse stages than during other
      stages. This shows that impasse reports might be unreliable indicators of
      impasse. Our study highlights the importance of individual analysis of problem
      solving behavior to verify insight theory. 

PMID- 26300795
TI  - Observing the restriction of another person: vicarious reactance and the role of
      self-construal and culture.
AB  - Psychological reactance occurs in response to threats posed to perceived
      behavioral freedoms. Research has shown that people can also experience vicarious
      reactance. They feel restricted in their own freedom even though they are not
      personally involved in the restriction but only witness the situation. The
      phenomenon of vicarious reactance is especially interesting when considered in a
      cross-cultural context because the cultural specific self-construal plays a
      crucial role in understanding people's response to self- and vicariously
      experienced restrictions. Previous studies and our pilot study (N = 197) could
      show that people with a collectivistic cultural background show higher vicarious
      reactance compared to people with an individualistic cultural background. But
      does it matter whether people experience the vicarious restriction for an in
      group or an out-group member? Differentiating vicarious-in-group and vicarious
      out-group restrictions, Study 1 (N = 159) suggests that people with a more
      interdependent self-construal show stronger vicarious reactance only with regard
      to in-group restrictions but not with regard to out-group restrictions. In
      contrast, participants with a more independent self-construal experience stronger
      reactance when being self-restricted compared to vicariously-restricted. Study 2
      (N = 180) replicates this pattern conceptually with regard to individualistic and
      collectivistic cultural background groups. Additionally, participants' behavioral
      intentions show the same pattern of results. Moreover a mediation analysis
      demonstrates that cultural differences in behavioral intentions could be
      explained through people's self-construal differences. Thus, the present studies
      provide new insights and show consistent evidence for vicarious reactance
      depending on participants' culturally determined self-construal. 

PMID- 26300796
TI  - Intrinsic and extrinsic motivation is associated with computer-based auditory
      training uptake, engagement, and adherence for people with hearing loss.
AB  - Hearing aid intervention typically occurs after significant delay, or not at all,
      resulting in an unmet need for many people with hearing loss. Computer-based
      auditory training (CBAT) may provide generalized benefits to real-world
      listening, particularly in adverse listening conditions, and can be conveniently
      delivered in the home environment. Yet as with any intervention, adherence to
      CBAT is critical to its success. The main aim of this investigation was to
      explore motivations for uptake, engagement and adherence with home-delivered CBAT
      in a randomized controlled trial of adults with mild sensorineural hearing loss
      (SNHL), with a view to informing future CBAT development. A secondary aim
      examined perceived benefits of CBAT. Participants (n = 44, 50-74 years olds with
      mild SNHL who did not have hearing aids) completed a 4-week program of phoneme
      discrimination CBAT at home. Participants' experiences of CBAT were captured
      using a post-training questionnaire (n = 44) and two focus groups (n = 5 per
      group). A mixed-methods approach examined participants' experiences with the
      intervention, the usability and desirability of the CBAT software, and
      participants' motivations for CBAT uptake, engagement and adherence. Self
      Determination Theory (SDT) was used as a theoretical framework for the
      interpretation of results. Participants found the CBAT intervention easy to use,
      interesting and enjoyable. Initial participation in the study was associated with
      extrinsic motivation (e.g., hearing difficulties). Engagement and adherence with
      CBAT was influenced by intrinsic (e.g., a desire to achieve higher scores), and
      extrinsic (e.g., to help others with hearing loss) motivations. Perceived post
      training benefits included better concentration and attention leading to improved
      listening. CBAT also prompted further help-seeking behaviors for some
      individuals. We see this as an important first-step for informing future theory
      driven development of effective CBAT interventions. 

PMID- 26300797
TI  - Keeping in touch with the visual system: spatial alignment and multisensory
      integration of visual-somatosensory inputs.
AB  - Correlated sensory inputs coursing along the individual sensory processing
      hierarchies arrive at multisensory convergence zones in cortex where inputs are
      processed in an integrative manner. The exact hierarchical level of multisensory
      convergence zones and the timing of their inputs are still under debate, although
      increasingly, evidence points to multisensory integration (MSI) at very early
      sensory processing levels. While MSI is said to be governed by stimulus
      properties including space, time, and magnitude, violations of these rules have
      been documented. The objective of the current study was to determine, both
      psychophysically and electrophysiologically, whether differential visual
      somatosensory (VS) integration patterns exist for stimuli presented to the same
      versus opposite hemifields. Using high-density electrical mapping and
      complementary psychophysical data, we examined multisensory integrative
      processing for combinations of visual and somatosensory inputs presented to both
      left and right spatial locations. We assessed how early during sensory processing
      VS interactions were seen in the event-related potential and whether spatial
      alignment of the visual and somatosensory elements resulted in differential
      integration effects. Reaction times to all VS pairings were significantly faster
      than those to the unisensory conditions, regardless of spatial alignment,
      pointing to engagement of integrative multisensory processing in all conditions.
      In support, electrophysiological results revealed significant differences between
      multisensory simultaneous VS and summed V + S responses, regardless of the
      spatial alignment of the constituent inputs. Nonetheless, multisensory effects
      were earlier in the aligned conditions, and were found to be particularly robust
      in the case of right-sided inputs (beginning at just 55 ms). In contrast to
      previous work on audio-visual and audio-somatosensory inputs, the current work
      suggests a degree of spatial specificity to the earliest detectable multisensory
      integrative effects in response to VS pairings. 

PMID- 26300799
TI  - Confounding dynamic risk taking propensity with a momentum prognostic strategy:
      the case of the Columbia Card Task (CCT).
AB  - Figner et al. (2009) developed the Columbia Card Task (CCT) to measure risk
      taking attitudes. This tool consists of two versions: in the COLD version the
      decision maker needs to state in advance how many cards (out of 32) they want to
      turn over (so called static risk taking), in the HOT version they have the
      possibility of turning over all 32 cards one-by-one until they decide to finish
      (dynamic risk taking). We argue that the HOT version confounds an individual's
      willingness to accept risk with their beliefs in trend continuation vs. trend
      reversal in a prognostic task. In two experimental studies we show that people
      believing in trend continuation (momentum subjects) turn over more cards than
      those believing in trend reversal (contrarians) in the HOT version of the task.
      However, this is not the case in the COLD version. Thus, we provide evidence
      that, when considered as a dynamic risk propensity measure, the number of turned
      over cards in the HOT version of the CCT is a contaminated measure and reflects
      two phenomena: (1) risk preference and (2) the decision-maker's belief in trend
      continuation. We speculate that other dynamic risk taking measures can also be
      biased by a momentum strategy. 

PMID- 26300798
TI  - Developing Bayesian adaptive methods for estimating sensitivity thresholds (d')
      in Yes-No and forced-choice tasks.
AB  - Motivated by Signal Detection Theory (SDT), we developed a family of novel
      adaptive methods that estimate the sensitivity threshold-the signal intensity
      corresponding to a pre-defined sensitivity level (d' = 1)-in Yes-No (YN) and
      Forced-Choice (FC) detection tasks. Rather than focus stimulus sampling to
      estimate a single level of %Yes or %Correct, the current methods sample
      psychometric functions more broadly, to concurrently estimate sensitivity and
      decision factors, and thereby estimate thresholds that are independent of
      decision confounds. Developed for four tasks-(1) simple YN detection, (2) cued YN
      detection, which cues the observer's response state before each trial, (3) rated
      YN detection, which incorporates a Not Sure response, and (4) FC detection-the
      qYN and qFC methods yield sensitivity thresholds that are independent of the
      task's decision structure (YN or FC) and/or the observer's subjective response
      state. Results from simulation and psychophysics suggest that 25 trials (and
      sometimes less) are sufficient to estimate YN thresholds with reasonable
      precision (s.d. = 0.10-0.15 decimal log units), but more trials are needed for FC
      thresholds. When the same subjects were tested across tasks of simple, cued,
      rated, and FC detection, adaptive threshold estimates exhibited excellent
      agreement with the method of constant stimuli (MCS), and with each other. These
      YN adaptive methods deliver criterion-free thresholds that have previously been
      exclusive to FC methods. 

PMID- 26300800
TI  - Neurolinguistic measures of typological effects in multilingual transfer:
      introducing an ERP methodology.
AB  - This article has two main objectives. First, we offer an introduction to the
      subfield of generative third language (L3) acquisition. Concerned primarily with
      modeling initial stages transfer of morphosyntax, one goal of this program is to
      show how initial stages L3 data make significant contributions toward a better
      understanding of how the mind represents language and how (cognitive) economy
      constrains acquisition processes more generally. Our second objective is to argue
      for and demonstrate how this subfield will benefit from a neuro/psycholinguistic
      methodological approach, such as event-related potential experiments, to
      complement the claims currently made on the basis of exclusively behavioral
      experiments. 

PMID- 26300801
TI  - Fifteen-month-old infants use velocity information to predict others' action
      targets.
AB  - In a world full of objects, predicting which object a person is going to grasp is
      not easy for an onlooker. Among other cues, the characteristics of a reaching
      movement might be informative for predicting its target, as approach movements
      are slower when more accuracy is required. The current study examined whether
      observers can predict the target of an action based on the movement velocity
      while the action is still unfolding, and if so, whether these predictions are
      likely the result of motor simulation. We investigated the role of motor
      processes for velocity-based predictions by studying participants who based on
      their age differed in motor experience with the task at hand, namely reaching. To
      that end, 9-, 12-, and 15-month-old infants and a group of adults participated in
      an eye-tracking experiment which assessed action prediction accuracy.
      Participants observed a hand repeatedly moving toward and pressing a button on a
      panel, one of which was small, the other one large. The velocity of the reaching
      hand was the central cue for predicting which button would be the target of the
      observed action as the velocity was lower when reaching for the small compared to
      the large button. Adults and 15-month-old infants made more frequent visual
      anticipations to the close button when it was the target than when it was not and
      were thus able to use the information in the speed of the approach movement for
      the prediction of the action target. The 9- and 12-month-olds, however, did not
      display this difference. After the eye-tracking experiment, infants' ability to
      aim for and press buttons of different sizes was evaluated. Results showed that
      the 15-month-olds were more proficient than the 9- and 12-month-olds in
      performing the reaching actions. The developmental time line of velocity-based
      action predictions thus corresponds to the development of performing that motor
      act yourself. Taken together, these data suggest that motor simulation may
      underlie velocity-based predictions. 

PMID- 26300803
TI  - Cognitive strategy interventions improve word problem solving and working memory
      in children with math disabilities.
AB  - This study investigated the role of strategy instruction and working memory
      capacity (WMC) on problem solving solution accuracy in children with and without
      math disabilities (MD). Children in grade 3 (N = 204) with and without MD
      subdivided into high and low WMC were randomly assigned to 1 of 4 conditions:
      verbal strategies (e.g., underlining question sentence), visual strategies (e.g.,
      correctly placing numbers in diagrams), verbal + visual strategies, and an
      untreated control. The dependent measures for training were problem solving
      accuracy and two working memory transfer measures (operation span and visual
      spatial span). Three major findings emerged: (1) strategy instruction facilitated
      solution accuracy but the effects of strategy instruction were moderated by WMC,
      (2) some strategies yielded higher post-test scores than others, but these
      findings were qualified as to whether children were at risk for MD, and (3)
      strategy training on problem solving measures facilitated transfer to working
      memory measures. The main findings were that children with MD, but high WM spans,
      were more likely to benefit from strategy conditions on target and transfer
      measures than children with lower WMC. The results suggest that WMC moderates the
      influence of cognitive strategies on both the targeted and non-targeted measures.

PMID- 26300802
TI  - Mild cognitive impairment and fMRI studies of brain functional connectivity: the
      state of the art.
AB  - In the last 15 years, many articles have studied brain connectivity in Mild
      Cognitive Impairment patients with fMRI techniques, seemingly using different
      connectivity statistical models in each investigation to identify complex
      connectivity structures so as to recognize typical behavior in this type of
      patient. This diversity in statistical approaches may cause problems in results
      comparison. This paper seeks to describe how researchers approached the study of
      brain connectivity in MCI patients using fMRI techniques from 2002 to 2014. The
      focus is on the statistical analysis proposed by each research group in reference
      to the limitations and possibilities of those techniques to identify some
      recommendations to improve the study of functional connectivity. The included
      articles came from a search of Web of Science and PsycINFO using the following
      keywords: f MRI, MCI, and functional connectivity. Eighty-one papers were found,
      but two of them were discarded because of the lack of statistical analysis.
      Accordingly, 79 articles were included in this review. We summarized some parts
      of the articles, including the goal of every investigation, the cognitive
      paradigm and methods used, brain regions involved, use of ROI analysis and
      statistical analysis, emphasizing on the connectivity estimation model used in
      each investigation. The present analysis allowed us to confirm the remarkable
      variability of the statistical analysis methods found. Additionally, the study of
      brain connectivity in this type of population is not providing, at the moment,
      any significant information or results related to clinical aspects relevant for
      prediction and treatment. We propose to follow guidelines for publishing fMRI
      data that would be a good solution to the problem of study replication. The
      latter aspect could be important for future publications because a higher
      homogeneity would benefit the comparison between publications and the
      generalization of results. 

PMID- 26300804
TI  - Treating the mind to improve the heart: the summon to cardiac psychology.

PMID- 26300805
TI  - Differences in exercise intensity seems to influence the affective responses in
      self-selected and imposed exercise: a meta-analysis.
AB  - Self-selected exercise seems to promote positive affective responses due to the
      perceived autonomy associated with it. The objective of the present study was to
      determine the magnitude of differences in Feeling Scale (FS) responses during
      self-selected and imposed exercise sessions. The PRISMA Statement was adopted for
      this meta-analysis. The search used PubMed, Scopus, PsycINFO, and ISI Web of
      Knowledge databases. A total of 10 studies that compared the effects of self
      selected and imposed exercise sessions on acute FS responses were included. The
      screening strategy included: exclusion of studies that were duplicated between
      databases, abstract screening, and text screening. The standardized mean
      difference (SMD) between self-selected and imposed exercise sessions categorized
      in five intensities (equal intensity: both exercises were performed at the same
      intensity, below lactate/ventilatory threshold (LT/VT): imposed exercise was
      performed at an intensity below the LT/VT, at LT/VT: imposed exercise was
      performed at the LT/VT intensity, above LT/VT: imposed exercise was performed at
      an intensity above the LT/VT, and different intensity: both exercises were
      performed at different intensities and the intensity of imposed session was not
      reported relative to LT/VT) and an overall SMD were calculated. Self-selected
      exercise was used as the reference condition. The subtotal SMD values were as
      follows: -0.10 (equal intensity), -0.36 (below LT/VT), -0.57 (at LT/VT), -1.30
      (above LT/VT), and -0.09 (different intensity) and the overall SMD was -0.41. The
      results of the present study indicate that the difference between affective
      responses in self-selected and imposed exercise sessions is dependent on the
      intensity of the imposed exercise session. 

PMID- 26300806
TI  - Feel like you belong: on the bidirectional link between emotional fit and group
      identification in task groups.
AB  - Three studies investigated the association between members' group identification
      and the emotional fit with their group. In the first study, a cross-sectional
      study in a large organization, we replicated earlier research by showing that
      group identification and emotional fit are positively associated, using a broader
      range of emotions and using profile correlations to measure group members'
      emotional fit. In addition, in two longitudinal studies, where groups of students
      were followed at several time points during their collaboration on a project, we
      tested the directionality of the relationship between group identification and
      emotional fit. The results showed a bidirectional, positive link between group
      identification and emotional fit, such that group identification and emotional
      fit either mutually reinforce or mutually dampen each other over time. We discuss
      how these findings increase insights in group functioning and how they may be
      used to change group processes for better or worse. 

PMID- 26300808
TI  - The classification of psychiatric disorders according to DSM-5 deserves an
      internationally standardized psychological test battery on symptom level.

PMID- 26300807
TI  - Perception of temporal asymmetries in dynamic facial expressions.
AB  - In the current study we examined whether timeline-reversals and emotional
      direction of dynamic facial expressions affect subjective experience of human
      observers. We recorded natural movies of faces that increased or decreased their
      expressions of fear, and played them either in the natural frame order or
      reversed from last to first frame (reversed timeline). This led to four
      conditions of increasing or decreasing fear, either following the natural or
      reversed temporal trajectory of facial dynamics. This 2-by-2 factorial design
      controlled for visual low-level properties, static visual content, and motion
      energy across the different factors. It allowed us to examine perceptual
      consequences that would occur if the timeline trajectory of facial muscle
      movements during the increase of an emotion are not the exact mirror of the
      timeline during the decrease. It additionally allowed us to study perceptual
      differences between increasing and decreasing emotional expressions. Perception
      of these time-dependent asymmetries have not yet been quantified. We found that
      three emotional measures, emotional intensity, artificialness of facial movement,
      and convincingness or plausibility of emotion portrayal, were affected by
      timeline-reversals as well as by the emotional direction of the facial
      expressions. Our results imply that natural dynamic facial expressions contain
      temporal asymmetries, and show that deviations from the natural timeline lead to
      a reduction of perceived emotional intensity and convincingness, and to an
      increase of perceived artificialness of the dynamic facial expression. In
      addition, they show that decreasing facial expressions are judged as less
      plausible than increasing facial expressions. Our findings are of relevance for
      both, behavioral as well as neuroimaging studies, as processing and perception
      are influenced by temporal asymmetries. 

PMID- 26300809
TI  - Second language social networks and communication-related acculturative stress:
      the role of interconnectedness.
AB  - Although a substantial amount of cross-cultural psychology research has
      investigated acculturative stress in general, little attention has been devoted
      specifically to communication-related acculturative stress (CRAS). In line with
      the view that cross-cultural adaptation and second language (L2) learning are
      social and interpersonal phenomena, the present study examines the hypothesis
      that migrants' L2 social network size and interconnectedness predict CRAS. The
      main idea underlying this hypothesis is that L2 social networks play an important
      role in fostering social and cultural aspects of communicative competence.
      Specifically, higher interconnectedness may reflect greater access to unmodified
      natural cultural representations and L2 communication practices, thus fostering
      communicative competence through observational learning. As such, structural
      aspects of migrants' L2 social networks may be protective against acculturative
      stress arising from chronic communication difficulties. Results from a study of
      first generation migrant students (N = 100) support this idea by showing that
      both inclusiveness and density of the participants' L2 network account for unique
      variance in CRAS but not in general acculturative stress. These results support
      the idea that research on cross-cultural adaptation would benefit from
      disentangling the various facets of acculturative stress and that the structure
      of migrants' L2 network matters for language related outcomes. Finally, this
      study contributes to an emerging body of work that attempts to integrate
      cultural/cross-cultural research on acculturation and research on intercultural
      communication and second language learning. 

PMID- 26300810
TI  - Commentary "Reinstatement of long-term memory following erasure of its behavioral
      and synaptic expression in Aplysia".

PMID- 26300811
TI  - Testing Theory of Planned Behavior and Neo-Socioanalytic Theory models of trait
      activity, industriousness, exercise social cognitions, exercise intentions, and
      physical activity in a representative U.S. sample.
AB  - Prior research identified assorted relations between trait and social cognition
      models of personality and engagement in physical activity. Using a representative
      U.S. sample (N = 957), the goal of the present study was to test two alternative
      structural models of the relationships among the extraversion-related facet of
      activity, the conscientiousness-related facet of industriousness, social
      cognitions from the Theory of Planned Behavior (perceived behavioral control,
      affective attitudes, subjective norms, intentions), Social Cognitive Theory (self
      efficacy, outcome expectancies), and the Transtheoretical Model (behavioral
      processes of change), and engagement in physical activity. Path analyses with
      bootstrapping procedures were used to model direct and indirect effects of trait
      and social cognition constructs on physical activity through two distinct
      frameworks - the Theory of Planned Behavior and Neo-Socioanalytic Theory. While
      both models showed good internal fit, comparative model information criteria
      showed the Theory-of-Planned-Behavior-informed model provided a better fit. In
      the model, social cognitions fully mediated the relationships from the activity
      facet and industriousness to intentions for and engagement in physical activity,
      such that the relationships were primarily maintained by positive affective
      evaluations, positive expected outcomes, and confidence in overcoming barriers
      related to physical activity engagement. The resultant model - termed the
      Disposition-Belief-Motivation model- is proposed as a useful framework for
      organizing and integrating personality trait facets and social cognitions from
      various theoretical perspectives to investigate the expression of health-related
      behaviors, such as physical activity. Moreover, the results are discussed in
      terms of extending the application of the Disposition-Belief-Motivation model to
      longitudinal and intervention designs for physical activity engagement. 

PMID- 26300812
TI  - Effect of fragrance use on discrimination of individual body odor.
AB  - Previous research suggests that artificial fragrances may be chosen to complement
      or enhance an individual's body odor, rather than simply masking it, and that
      this may create an odor blend with an emergent quality that is perceptually
      distinguishable from body odor or fragrance alone. From this, it can be predicted
      that a new emergent odor might be more easily identified than an individual's
      body odor in isolation. We used a triangle test paradigm to assess whether
      fragrance affects people's ability to distinguish between individual odors. Six
      male and six female donors provided axillary odor samples in three conditions
      (without fragrance, wearing their own fragrance, and wearing an assigned
      fragrance). In total, 296 female and 131 male participants selected the odd one
      from three odor samples (two from one donor, one from another; both of the same
      sex). We found that participants could discriminate between the odors at above
      chance levels in all three odor conditions. Olfactory identification ability
      (measured using Sniffin' Sticks) positively predicted discrimination performance,
      and sex differences in performance were also observed, with female raters being
      correct more often than men. Success rates were also higher for odors of male
      donors. Additionally, while performance was above chance in all conditions,
      individual odor discrimination varied across the three conditions. Discrimination
      rate was significantly higher in the "no fragrance" condition than either of the
      fragranced conditions. Importantly, however, discrimination rate was also
      significantly higher in the "own fragrance" condition than the "assigned
      fragrance" condition, suggesting that naturally occurring variance in body odor
      is more preserved when blended with fragrances that people choose for themselves,
      compared with other fragrances. Our data are consistent with the idea that
      fragrance choices are influenced by fragrance interactions with an individual's
      own body odor. 

PMID- 26300813
TI  - Statistics anxiety and performance: blessings in disguise.

PMID- 26300814
TI  - Symptom severity of depressive symptoms impacts on social cognition performance
      in current but not remitted major depressive disorder.
AB  - The aim of the present study was to investigate the social cognitive functioning
      of participants with depression when compared with healthy controls, and to
      assess the impact of symptom severity. One hundred and eight patients with
      depression (66 remitted and 42 current) and 52 healthy controls were assessed
      using the Wechsler Advanced Clinical Solutions: Social Perception Subtest,
      measuring facial affect recognition in isolation and in combination with prosody
      and body language interpretation. When healthy controls, remitted depression and
      currently depressed groups were compared, no associations were found on any of
      the social cognition subscales. Severity of depressive and anxious symptoms
      predicted performance on all social cognition subscales in currently depressed
      participants, controlling for age, gender, education and psychotropic medication.
      Affective depressive symptoms were inversely related to ACS Pairs and Prosody
      subscales, while somatic symptoms were inversely related to the ACS Affect
      Recognition and Total scores. There was no association between severity and the
      WAIS ACS in remitted depression participants. People with MDD exhibiting more
      severe depressive and anxious symptoms and a cluster of affective symptoms have
      greater difficulty undertaking complex social cognitive tasks. Given the state
      like nature to these deficits, these impairments may cause problems with day to
      day functioning and have implications in targeted therapeutic interventions. 

PMID- 26300816
TI  - Is it time for studying real-life debiasing? Evaluation of the effectiveness of
      an analogical intervention technique.
AB  - The aim of this study was to initiate the exploration of debiasing methods
      applicable in real-life settings for achieving lasting improvement in decision
      making competence regarding multiple decision biases. Here, we tested the
      potentials of the analogical encoding method for decision debiasing. The
      advantage of this method is that it can foster the transfer from learning
      abstract principles to improving behavioral performance. For the purpose of the
      study, we devised an analogical debiasing technique for 10 biases (covariation
      detection, insensitivity to sample size, base rate neglect, regression to the
      mean, outcome bias, sunk cost fallacy, framing effect, anchoring bias,
      overconfidence bias, planning fallacy) and assessed the susceptibility of the
      participants (N = 154) to these biases before and 4 weeks after the training. We
      also compared the effect of the analogical training to the effect of 'awareness
      training' and a 'no-training' control group. Results suggested improved
      performance of the analogical training group only on tasks where the violations
      of statistical principles are measured. The interpretation of these findings
      require further investigation, yet it is possible that analogical training may be
      the most effective in the case of learning abstract concepts, such as statistical
      principles, which are otherwise difficult to master. The study encourages a
      systematic research of debiasing trainings and the development of intervention
      assessment methods to measure the endurance of behavior change in decision
      debiasing. 

PMID- 26300815
TI  - Space-based and object-centered gaze cuing of attention in right hemisphere
      damaged patients.
AB  - Gaze cuing of attention is a well established phenomenon consisting of the
      tendency to shift attention to the location signaled by the averted gaze of other
      individuals. Evidence suggests that such phenomenon might follow intrinsic object
      centered features of the head containing the gaze cue. In the present exploratory
      study, we aimed to investigate whether such object-centered component is present
      in neuropsychological patients with a lesion involving the right hemisphere,
      which is known to play a critical role both in orienting of attention and in face
      processing. To this purpose, we used a modified gaze-cuing paradigm in which a
      centrally placed head with averted gaze was presented either in the standard
      upright position or rotated 90 degrees  clockwise or anti-clockwise. Afterward, a
      to-be-detected target was presented either in the right or in the left hemifield.
      The results showed that gaze cuing of attention was present only when the target
      appeared in the left visual hemifield and was not modulated by head orientation.
      This suggests that gaze cuing of attention in right hemisphere-damaged patients
      can operate within different frames of reference. 

PMID- 26300817
TI  - Animal-Assisted Intervention for trauma: a systematic literature review.
AB  - Animals have a long history of inclusion in psychiatric treatment. There has been
      a recent growth in the empirical study of this practice, known as Animal-Assisted
      Intervention (AAI). We conducted a systematic review of the empirical literature
      on AAI for trauma, including posttraumatic stress disorder (PTSD). Ten studies
      qualified for inclusion, including six peer-reviewed journal articles and four
      unpublished theses. Participants were predominantly survivors of child abuse, in
      addition to military veterans. The presentation of AAI was highly variable across
      the studies. The most common animal species were dogs and horses. The most
      prevalent outcomes were reduced depression, PTSD symptoms, and anxiety. There was
      a low level of methodological rigor in most studies, indicating the preliminary
      nature of this area of investigation. We conclude that AAI may provide promise as
      a complementary treatment option for trauma, but that further research is
      essential to establish feasibility, efficacy, and manualizable protocols. 

PMID- 26300818
TI  - Training for generalization in Theory of Mind: a study with older adults.
AB  - Theory of Mind (ToM) refers to the ability to attribute independent mental states
      to self and others in order to explain and predict social behavior. Recent
      research in this area has shown a decline in ToM abilities associated with normal
      aging that is of a moderate magnitude or greater. Very few studies have
      investigated whether it is possible to improve older adults' ToM abilities. The
      present study was designed to address this gap in the literature by evaluating
      the impact of a ToM training on practiced and transfer tasks. We provided older
      adults with a variety of activities designed to facilitate the generalization of
      benefits to other ToM-demanding tasks. Participants were 63 healthy older adults,
      native Italian speakers (M age = 71.44, SD = 5.24, age range: 63-81 years).
      Participants were randomly assigned to one of two groups: the ToM training (age
      range: 63-81 years) and the physical-conversation training (age range: 64-81
      years). Training effects were measured using the strange stories (practiced task)
      and the animation task (transfer task). Results revealed the efficacy of the
      training in producing improvements on practiced but also on transfer tasks. 

PMID- 26300819
TI  - Facial beauty affects implicit and explicit learning of men and women
      differently.
AB  - The present work explores the unconscious and/or conscious nature of learning
      attractive faces of same and opposite sex, that is, of stimuli that experimental
      and neuroimaging research has shown to be rewarding and thus highly motivating.
      To this end, we examined performance of men and women while classifying strings
      of average and attractive faces for grammaticality in the experimental task of
      artificial grammar learning (AGL), which reflects both conscious and unconscious
      processes. Subjective measures were used to assess participants' conscious and
      unconscious knowledge. It was found that female attractiveness impaired
      performance in male participants. In particular, male participants demonstrated
      the lowest accuracy while classifying beautiful faces of women. Conversely,
      female attractiveness facilitated performance in female participants. The pattern
      was similar for conscious and unconscious knowledge. Presumably, objects with
      high incentive salience, as are beautiful faces, captured resources, which were
      used in task relevant versus task irrelevant ways by women versus men. The
      present findings shed light on the relation of conscious and unconscious
      processing with affective and reward-related stimuli, as well as on gender
      differences underlying this relation. 

PMID- 26300820
TI  - In the moral eye of the beholder: the interactive effects of leader and follower
      moral identity on perceptions of ethical leadership and LMX quality.
AB  - Previous research indicated that leader moral identity (MI; i.e., leaders' self
      definition in terms of moral attributes) predicts to what extent followers
      perceive their leader as ethical (i.e., demonstrating and promoting ethical
      conduct in the organization). Leadership, however, is a relational process that
      involves leaders and followers. Building on this understanding, we hypothesized
      that follower and leader MI (a) interact in predicting whether followers will
      perceive their leaders as ethical and, as a result, (b) influence followers'
      perceptions of leader-follower relationship quality. A dyadic field study (N =
      101) shows that leader MI is a stronger predictor of followers' perceptions of
      ethical leadership for followers who are high (vs. low) in MI. Perceptions of
      ethical leadership in turn predict how the quality of the relationship will be
      perceived. Hence, whether leader MI translates to perceptions of ethical
      leadership and of better relationship quality depends on the MI of followers. 

PMID- 26300823
TI  - Self-report measures of executive functioning are a determinant of academic
      performance in first-year students at a university of applied sciences.
AB  - Recent studies in late adolescents (age 17+) show that brain development may
      proceed till around the 25th year of age. This implies that study performance in
      higher education could be dependent upon the stage of brain maturation and
      neuropsychological development. Individual differences in development of
      neuropsychological skills may thus have a substantial influence on the outcome of
      the educational process. This hypothesis was evaluated in a large survey of 1760
      first-year students at a University of Applied Sciences, of which 1332 are
      included in the current analyses. This was because of their fit within the age
      range we pre-set (17-20 years' old at start of studies). Student characteristics
      and three behavioral ratings of executive functioning (EF) were evaluated with
      regard to their influence on academic performance. Self-report measures were
      used: self-reported attention, planning, and self-control and self-monitoring.
      Results showed that students with better self-reported EF at the start of the
      first year of their studies obtained more study credits at the end of that year
      than students with a lower EF self-rating. The correlation between self-control
      and self-monitoring on the one hand, and study progress on the other, appeared to
      differ for male and female students and to be influenced by the level of prior
      education. The results of this large-scale study could have practical relevance.
      The profound individual differences between students may at least partly be a
      consequence of their stage of development as an adolescent. Students who show
      lower levels of attention control, planning, and self-control/self-monitoring can
      be expected to have a problem in study planning and study progress monitoring and
      hence study progress. The findings imply that interventions directed at the
      training of these (executive) functions should be developed and used in higher
      education in order to improve academic achievement, learning attitude, and
      motivation. 

PMID- 26300822
TI  - Aging and emotional expressions: is there a positivity bias during dynamic
      emotion recognition?
AB  - In this study, we investigated whether age-related differences in emotion
      regulation priorities influence online dynamic emotional facial discrimination. A
      group of 40 younger and a group of 40 older adults were invited to recognize a
      positive or negative expression as soon as the expression slowly emerged and
      subsequently rate it in terms of intensity. Our findings show that older adults
      recognized happy expressions faster than angry ones, while the direction of
      emotional expression does not seem to affect younger adults' performance.
      Furthermore, older adults rated both negative and positive emotional faces as
      more intense compared to younger controls. This study detects age-related
      differences with a dynamic online paradigm and suggests that different regulation
      strategies may shape emotional face recognition. 

PMID- 26300821
TI  - Bringing the "self" into focus: conceptualising the role of self-experience for
      understanding and working with distressing voices.
AB  - A primary goal of cognitive behavior therapy for psychosis (CBTp) is to reduce
      distress and disability, not to change the positive symptoms of psychosis, such
      as hearing voices. Despite demonstrated associations between beliefs about voices
      and distress, the effects of CBTp on reducing voice distress are disappointing.
      Research has begun to explore the role that the psychological construct of "self"
      (which includes numerous facets such as self-reflection, self-schema and self
      concept) might play in causing and maintaining distress and disability in voice
      hearers. However, attempts to clarify and integrate these different perspectives
      within the voice hearing literature, or to explore their clinical implications,
      are still in their infancy. This paper outlines how the self has been
      conceptualised in the psychosis and CBT literatures, followed by a review of the
      evidence regarding the proposed role of this construct in the etiology of and
      adaptation to voice hearing experiences. We go on to discuss some of the specific
      intervention methods that aim to target these aspects of self-experience and end
      by identifying key research questions in this area. Notably, we suggest that
      interventions specifically targeting aspects of self-experience, including self
      affection, self-reflection, self-schema and self-concept, may be sufficient to
      reduce distress and disruption in the context of hearing voices, a suggestion
      that now requires further empirical investigation. 

PMID- 26300824
TI  - Are maternal reflective functioning and attachment security associated with
      preadolescent mentalization?
AB  - This study investigated the impact of maternal reflective functioning (RF) and
      attachment security on children's mentalization. The Adult Attachment Interview
      (AAI) was administered to mothers in a sample of 41 mother-preadolescent dyads.
      AAI transcripts were rated in terms of the Berkeley AAI System (Main and Goldwyn,
      1998) and the Reflective Functioning Scale (RFS; Fonagy et al., 1998).
      Preadolescent mentalization was assessed using a semi-structured interview
      adapted from O'Connor and Hirsch (1999) and also by analyzing mental-state talk
      produced during an autobiographical interview. Relationships between maternal RF
      and children's mentalization were analyzed, with consideration given to the
      different RFS markers and references to positive, negative, and mixed-ambivalent
      mental states. Children's mentalization was positively correlated with the
      mother's RF, particularly the mother's ability to mentalize negative or mixed
      ambivalent mental states. No significant differences in mentalization were
      observed between children of secure and insecure mothers. 

PMID- 26300825
TI  - The sounds of safety: stress and danger in music perception.
AB  - As with any sensory input, music might be expected to incorporate the processing
      of information about the safety of the environment. Little research has been done
      on how such processing has evolved and how different kinds of sounds may affect
      the experience of certain environments. In this article, we investigate if music,
      as a form of auditory information, can trigger the experience of safety. We
      hypothesized that (1) there should be an optimal, subjectively preferred degree
      of information density of musical sounds, at which safety-related information can
      be processed optimally; (2) any deviation from the optimum, that is, both higher
      and lower levels of information density, should elicit experiences of higher
      stress and danger; and (3) in general, sonic scenarios with music should reduce
      experiences of stress and danger more than other scenarios. In Experiment 1, the
      information density of short music-like rhythmic stimuli was manipulated via
      their tempo. In an initial session, listeners adjusted the tempo of the stimuli
      to what they deemed an appropriate tempo. In an ensuing session, the same
      listeners judged their experienced stress and danger in response to the same
      stimuli, as well as stimuli exhibiting tempo variants. Results are consistent
      with the existence of an optimum information density for a given rhythm; the
      preferred tempo decreased for increasingly complex rhythms. The hypothesis that
      any deviation from the optimum would lead to experiences of higher stress and
      danger was only partly fit by the data. In Experiment 2, listeners should
      indicate their experience of stress and danger in response to different sonic
      scenarios: music, natural sounds, and silence. As expected, the music scenarios
      were associated with lowest stress and danger whereas both natural sounds and
      silence resulted in higher stress and danger. Overall, the results largely fit
      the hypothesis that music seemingly carries safety-related information about the
      environment. 

PMID- 26300826
TI  - Infant manual performance during reaching and grasping for objects moving in
      depth.
AB  - Few studies have investigated manual performance in infants when reaching and
      grasping for objects moving in directions other than across the fronto-parallel
      plane. The present preliminary study explored object-oriented behavioral
      strategies and side preference in 8- and 10-month-old infants during reaching and
      grasping for objects approaching in depth from three positions (midline, and 27
      degrees  diagonally from the left and right). Effects of task constraint by using
      objects of three different types and two sizes were further examined for
      behavioral strategies and hand opening prior to grasping. Additionally,
      assessments of hand preference by a dedicated handedness test were performed.
      Regardless of object starting position, the 8-month-old infants predominantly
      displayed right-handed reaches for objects approaching in depth. In contrast, the
      older infants showed more varied strategies and performed more ipsilateral
      reaches in correspondence with the side of the approaching object. Conversely, 10
      month-old infants were more successful than the younger infants in grasping the
      objects, independent of object starting position. The findings regarding infant
      hand use strategies when reaching and grasping for objects moving in depth are
      similar to those from earlier studies using objects moving along a horizontal
      path. Still, initiation times of reaching onset were generally long in the
      present study, indicating that the object motion paths seemingly affected how the
      infants perceived the intrinsic properties and spatial locations of the objects,
      possibly with an effect on motor planning. Findings are further discussed in
      relation to future investigations of infant reaching and grasping for objects
      approaching in depth. 

PMID- 26300827
TI  - Occupational coping self-efficacy explains distress and well-being in nurses
      beyond psychosocial job characteristics.
AB  - AIM: The main purpose of the present study was to extend the Job Demand Control
      Support (JDCS) model analyzing the direct and interactive role of occupational
      coping self-efficacy (OCSE) beliefs. BACKGROUND: OCSE refers to an individual's
      beliefs about their ability to cope with occupational stressors. The interplay
      between occupational stressors, job resources, and self-efficacy beliefs is
      poorly investigated. The present research attempts to address this gap. DESIGN:
      Cross-sectional survey. METHOD: Questionnaire data from 1479 nurses (65%
      response) were analyzed. Hierarchical regression analyses were used to test the
      direct and moderating role of OCSE in conjunction with job demands (i.e., time
      pressure), and two job resources: job control (i.e., decision latitude and skill
      discretion) and social support (i.e., supervisor support and coworker support) in
      predicting psychological distress and well-being. RESULTS: Our findings indicated
      that high demands, low job control, and low social support additively predicted
      the distress/well-being outcomes (job satisfaction, emotional exhaustion,
      depersonalization, psychological distress, and somatic complaints). Beyond the
      main effects, no significant interactive effects of demands, control, and support
      were found. OCSE accounted for an additional 1-4% of the variance in the
      outcomes, after controlling for the JDCS variables. In addition, the results
      indicate that OCSE buffers the association between low job control and the
      distress dimensions emotional exhaustion, depersonalization, and psychological
      distress. Low control was detrimental only for nurses with low OCSE. CONCLUSION:
      Our results suggest expanding the JDCS model incorporating individual
      characteristics such as OCSE beliefs, for predicting psychological distress and
      well-being. Limitations of the study and practical implications are discussed.

PMID- 26300828
TI  - PERVALE-S: a new cognitive task to assess deaf people's ability to perceive basic
      and social emotions.
AB  - A poorly understood aspect of deaf people (DP) is how their emotional information
      is processed. Verbal ability is key to improve emotional knowledge in people.
      Nevertheless, DP are unable to distinguish intonation, intensity, and the rhythm
      of language due to lack of hearing. Some DP have acquired both lip-reading
      abilities and sign language, but others have developed only sign language.
      PERVALE-S was developed to assess the ability of DP to perceive both social and
      basic emotions. PERVALE-S presents different sets of visual images of a real deaf
      person expressing both basic and social emotions, according to the normative
      standard of emotional expressions in Spanish Sign Language. Emotional expression
      stimuli were presented at two different levels of intensity (1: low; and 2: high)
      because DP do not distinguish an object in the same way as hearing people (HP)
      do. Then, participants had to click on the more suitable emotional expression.
      PERVALE-S contains video instructions (given by a sign language interpreter) to
      improve DP's understanding about how to use the software. DP had to watch the
      videos before answering the items. To test PERVALE-S, a sample of 56 individuals
      was recruited (18 signers, 8 lip-readers, and 30 HP). Participants also performed
      a personality test (High School Personality Questionnaire adapted) and a fluid
      intelligence (Gf) measure (RAPM). Moreover, all deaf participants were rated by
      four teachers for the deaf. RESULTS: there were no significant differences
      between deaf and HP in performance in PERVALE-S. Confusion matrices revealed that
      embarrassment, envy, and jealousy were worse perceived. Age was just related to
      social-emotional tasks (but not in basic emotional tasks). Emotional perception
      ability was related mainly to warmth and consciousness, but negatively related to
      tension. Meanwhile, Gf was related to only social-emotional tasks. There were no
      gender differences.

PMID- 26300829
TI  - The relationships between interoception and alexithymic trait. The Self-Awareness
      Questionnaire in healthy subjects.
AB  - Interoception is the basic process enabling evaluation of one's own bodily
      states. Several previous studies suggested that altered interoception might be
      related to disorders in the ability to perceive and express emotions, i.e.,
      alexithymia, and to defects in perceiving and describing one's own health status,
      i.e., hypochondriasis. The main aim of the present study was to investigate the
      relationships between alexithymic trait and interoceptive abilities evaluated by
      the "Self-Awareness Questionnaire" (SAQ), a novel self-report tool for assessing
      interoceptive awareness. Two hundred and fifty healthy subjects completed the
      SAQ, the Toronto Alexithymia Scale-20 items (TAS-20), and a questionnaire to
      assess hypochondriasis, the Illness Attitude Scale (IAS). The SAQ showed a two
      factor structure, with good internal consistency (Cronbach's alpha = 0.88). We
      observed significant direct correlations between SAQ, TAS-20 and two of its
      subscales, and the IAS. Regression analysis confirmed that the difficulty in
      identifying and expressing emotions is significantly related with awareness for
      one's own interoceptive feelings and with a tendency to misinterpret and amplify
      bodily sensations. From a clinical point of view, the assessment of interoceptive
      awareness by the SAQ could be pivotal in evaluating several psychopathological
      conditions, such as the somatoform disorders. 

PMID- 26300832
TI  - A tragedy of the (academic) commons: interpreting the replication crisis in
      psychology as a social dilemma for early-career researchers.

PMID- 26300830
TI  - Interoceptive fear learning to mild breathlessness as a laboratory model for
      unexpected panic attacks.
AB  - Fear learning is thought to play an important role in panic disorder. Benign
      interoceptive sensations can become predictors (conditioned stimuli - CSs) of
      massive fear when experienced in the context of an initial panic attack
      (unconditioned stimulus - US). The mere encounter of these CSs on a later moment
      can induce anxiety and fear, and precipitate a new panic attack. It has been
      suggested that fear learning to interoceptive cues would result in unpredictable
      panic. The present study aimed to investigate whether fear learning to an
      interoceptive CS is possible without declarative knowledge of the CS-US
      contingency. The CS consisted of mild breathlessness (or: dyspnea), the US was a
      suffocation experience. During acquisition, the experimental group received six
      presentations of mild breathlessness immediately followed by suffocation; for the
      control group both experiences were always separated by an intertrial interval.
      In the subsequent extinction phase, participants received six unreinforced
      presentations of the CS. Expectancy of the US was rated continuously and startle
      eyeblink electromyographic, skin conductance, and respiration were measured.
      Declarative knowledge of the CS-US relationship was also assessed with a post
      experimental questionnaire. At the end of acquisition, both groups displayed the
      same levels of US expectancy and skin conductance in response to the CS, but the
      experimental group showed a fear potentiated startle eyeblink and a different
      respiratory response to the CS compared to the control group. Further analyses on
      a subgroup of CS-US unaware participants confirmed the presence of startle
      eyeblink conditioning in the experimental group but not in the control group. Our
      findings suggest that interoceptive fear learning is not dependent on declarative
      knowledge of the CS-US relationship. The present interoceptive fear conditioning
      paradigm may serve as an ecologically valid laboratory model for unexpected panic
      attacks. 

PMID- 26300831
TI  - Auditory stream segregation using amplitude modulated bandpass noise.
AB  - The purpose of this study was to investigate the roles of spectral overlap and
      amplitude modulation (AM) rate for stream segregation for noise signals, as well
      as to test the build-up effect based on these two cues. Segregation ability was
      evaluated using an objective paradigm with listeners' attention focused on stream
      segregation. Stimulus sequences consisted of two interleaved sets of bandpass
      noise bursts (A and B bursts). The A and B bursts differed in spectrum, AM-rate,
      or both. The amount of the difference between the two sets of noise bursts was
      varied. Long and short sequences were studied to investigate the build-up effect
      for segregation based on spectral and AM-rate differences. Results showed the
      following: (1). Stream segregation ability increased with greater spectral
      separation. (2). Larger AM-rate separations were associated with stronger
      segregation abilities. (3). Spectral separation was found to elicit the build-up
      effect for the range of spectral differences assessed in the current study. (4).
      AM-rate separation interacted with spectral separation suggesting an additive
      effect of spectral separation and AM-rate separation on segregation build-up. The
      findings suggest that, when normal-hearing listeners direct their attention
      towards segregation, they are able to segregate auditory streams based on reduced
      spectral contrast cues that vary by the amount of spectral overlap. Further,
      regardless of the spectral separation they are able to use AM-rate difference as
      a secondary/weaker cue. Based on the spectral differences, listeners can
      segregate auditory streams better as the listening duration is prolonged-i.e.,
      sparse spectral cues elicit build-up segregation; however, AM-rate differences
      only appear to elicit build-up when in combination with spectral difference cues.

PMID- 26300833
TI  - The aftermath of terrorism: posttraumatic stress and functional impairment after
      the 2011 Oslo bombing.
AB  - OBJECTIVE: In the present study we wanted to investigate the link between
      exposure, posttraumatic stress symptomatology, and functional impairment in the
      aftermath of terrorism. METHOD: Posttraumatic stress symptomatology and
      functional impairment related to the Oslo bombing 22nd of July, 2011, in directly
      and indirectly exposed individuals (N = 1927) were assessed together with
      demographics, exposure, peri-traumatic reactions, and event centrality
      approximately 1 year after the attack. RESULTS: Directly and indirectly exposed
      individuals qualifying for posttraumatic stress disorder (PTSD) reported similar
      peri-traumatic reactions, event centrality, and functional impairment. However,
      clusters within the PTSD symptomatology were differentially associated with
      impairment as a function of their exposure. In the directly exposed group, all
      clusters within the PTSD symptomatology were associated with impairment in
      function, while only emotional numbing was associated with impairment within the
      indirectly exposed group. CONCLUSION: Considering that terror attacks frequently
      involve directly exposed individuals and a larger population of indirectly
      exposed individuals, this finding is of importance, especially in the design of
      intervention programs and the development of treatment policies.

PMID- 26300834
TI  - Co-lateralized bilingual mechanisms for reading in single and dual language
      contexts: evidence from visual half-field processing of action words in
      proficient bilinguals.
AB  - When reading, proficient bilinguals seem to engage the same cognitive circuits
      regardless of the language in use. Yet, whether or not such "bilingual"
      mechanisms would be lateralized in the same way in distinct-single or dual
      language contexts is a question for debate. To fill this gap, we tested 18 highly
      proficient Polish (L1) -English (L2) childhood bilinguals whose task was to read
      aloud one of the two laterally presented action verbs, one stimulus per visual
      half field. While in the single-language blocks only L1 or L2 words were shown,
      in the subsequent mixed-language blocks words from both languages were
      concurrently displayed. All stimuli were presented for 217 ms followed by masks
      in which letters were replaced with hash marks. Since in non-simultaneous
      bilinguals the control of language, skilled actions (including reading), and
      representations of action concepts are typically left lateralized, the vast
      majority of our participants showed the expected, significant right visual field
      advantage for L1 and L2, both for accuracy and response times. The observed
      effects were nevertheless associated with substantial variability in the strength
      of the lateralization of the mechanisms involved. Moreover, although it could be
      predicted that participants' performance should be better in a single-language
      context, accuracy was significantly higher and response times were significantly
      shorter in a dual-language context, irrespective of the language tested. Finally,
      for both accuracy and response times, there were significant positive
      correlations between the laterality indices (LIs) of both languages independent
      of the context, with a significantly greater left-sided advantage for L1 vs. L2
      in the mixed-language blocks, based on LIs calculated for response times. Thus,
      despite similar representations of the two languages in the bilingual brain,
      these results also point to the functional separation of L1 and L2 in the dual
      language context. 

PMID- 26300835
TI  - Experiencing affective music in eyes-closed and eyes-open states: an
      electroencephalography study.
AB  - In real life, listening to music may be associated with an eyes-closed or eyes
      open state. The effect of eye state on listeners' reaction to music has attracted
      some attention, but its influence on brain activity has not been fully
      investigated. The present study aimed to evaluate the electroencephalographic
      (EEG) markers for the emotional valence of music in different eye states. Thirty
      participants listened to musical excerpts with different emotional content in the
      eyes-closed and eyes-open states. The results showed that participants rated the
      music as more pleasant or with more positive valence under an eyes-open state. In
      addition, we found that the alpha asymmetry indices calculated on the parietal
      and temporal sites reflected emotion valence in the eyes-closed and eyes-open
      states, respectively. The theta power in the frontal area significantly increased
      while listening to emotional-positive music compared to emotional-negative music
      under the eyes-closed condition. These effects of eye states on EEG markers are
      discussed in terms of brain mechanisms underlying attention and emotion. 

PMID- 26300836
TI  - Effect of training focused on executive functions (attention, inhibition, and
      working memory) in preschoolers exhibiting ADHD symptoms.
AB  - The development of early intervention strategies for children with symptoms of
      Attention Deficit Hyperactivity Disorder (ADHD) is important because it provides
      an opportunity to prevent severe problems in the future. The main purpose of this
      investigation was to determine the efficacy of a group training for the control
      of attention, working memory and impulsive behaviors, involving 5-year-old
      children with ADHD symptoms. Twenty-six children with ADHD symptoms and 26 with
      typical development were randomly divided in two conditions. Thirteen children in
      each group were assigned to the training condition and the other to the business
      as usual condition (normal class activity). Children who participated in the
      intervention showed an improvement in the tasks measuring their control of
      attention, impulsive behavior, and working memory. Moreover, children with
      typical development who attended the training also improved their competencies.
      The results confirm the importance of an early intervention for preschool-age
      children with ADHD symptoms. 

PMID- 26300837
TI  - Response actions influence the categorization of directions in auditory space.
AB  - Spatial region concepts such as "front," "back," "left," and "right" reflect our
      typical interaction with space, and the corresponding surrounding regions have
      different statuses in memory. We examined the representation of spatial
      directions in the auditory space, specifically in how far natural response
      actions, such as orientation movements toward a sound source, would affect the
      categorization of egocentric auditory space. While standing in the middle of a
      circle with 16 loudspeakers, participants were presented acoustic stimuli coming
      from the loudspeakers in randomized order, and verbally described their
      directions by using the concept labels "front," "back," "left," "right," "front
      right," "front-left," "back-right," and "back-left." Response actions varied in
      three blocked conditions: (1) facing front, (2) turning the head and upper body
      to face the stimulus, and (3) turning the head and upper body plus pointing with
      the hand and outstretched arm toward the stimulus. In addition to a protocol of
      the verbal utterances, motion capture and video recording generated a detailed
      corpus for subsequent analysis of the participants' behavior. Chi-square tests
      revealed an effect of response condition for directions within the left and right
      sides. We conclude that movement-based response actions influence the
      representation of auditory space, especially within the sides' regions. Moreover,
      the representation of auditory space favors the front and the back regions in
      terms of resolution, which is possibly related to the physiological
      characteristics of the human auditory system, as well as to the ecological
      requirements of action control in the different regions. 

PMID- 26300838
TI  - Developmental changes in analytic and holistic processes in face perception.
AB  - Although infants demonstrate sensitivity to some kinds of perceptual information
      in faces, many face capacities continue to develop throughout childhood. One
      debate is the degree to which children perceive faces analytically versus
      holistically and how these processes undergo developmental change. In the present
      study, school-aged children and adults performed a perceptual matching task with
      upright and inverted face and house pairs that varied in similarity of featural
      or 2(nd) order configural information. Holistic processing was operationalized as
      the degree of serial processing when discriminating faces and houses [i.e.,
      increased reaction time (RT), as more features or spacing relations were shared
      between stimuli]. Analytical processing was operationalized as the degree of
      parallel processing (or no change in RT as a function of greater similarity of
      features or spatial relations). Adults showed the most evidence for holistic
      processing (most strongly for 2(nd) order faces) and holistic processing was
      weaker for inverted faces and houses. Younger children (6-8 years), in contrast,
      showed analytical processing across all experimental manipulations. Older
      children (9-11 years) showed an intermediate pattern with a trend toward holistic
      processing of 2(nd) order faces like adults, but parallel processing in other
      experimental conditions like younger children. These findings indicate that
      holistic face representations emerge around 10 years of age. In adults both 2(nd)
      order and featural information are incorporated into holistic representations,
      whereas older children only incorporate 2(nd) order information. Holistic
      processing was not evident in younger children. Hence, the development of
      holistic face representations relies on 2(nd) order processing initially then
      incorporates featural information by adulthood. 

PMID- 26300839
TI  - Grounding the data. A response to: Population finiteness is not a concern for
      null hypothesis significance testing when studying human behavior.

PMID- 26300840
TI  - Looking under the hood of executive function impairments in psychopathology: A
      commentary on "Advancing understanding of executive function impairments and
      psychopathology: bridging the gap between clinical and cognitive approaches".

PMID- 26300841
TI  - To transform or not to transform: using generalized linear mixed models to
      analyse reaction time data.
AB  - Linear mixed-effect models (LMMs) are being increasingly widely used in
      psychology to analyse multi-level research designs. This feature allows LMMs to
      address some of the problems identified by Speelman and McGann (2013) about the
      use of mean data, because they do not average across individual responses.
      However, recent guidelines for using LMM to analyse skewed reaction time (RT)
      data collected in many cognitive psychological studies recommend the application
      of non-linear transformations to satisfy assumptions of normality. Uncritical
      adoption of this recommendation has important theoretical implications which can
      yield misleading conclusions. For example, Balota et al. (2013) showed that
      analyses of raw RT produced additive effects of word frequency and stimulus
      quality on word identification, which conflicted with the interactive effects
      observed in analyses of transformed RT. Generalized linear mixed-effect models
      (GLMM) provide a solution to this problem by satisfying normality assumptions
      without the need for transformation. This allows differences between individuals
      to be properly assessed, using the metric most appropriate to the researcher's
      theoretical context. We outline the major theoretical decisions involved in
      specifying a GLMM, and illustrate them by reanalysing Balota et al.'s datasets.
      We then consider the broader benefits of using GLMM to investigate individual
      differences. 

PMID- 26300842
TI  - Pro-Apoptotic Kinase Levels in Cerebrospinal Fluid as Potential Future Biomarkers
      in Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is characterized by the accumulation of Abeta peptides,
      hyperphosphorylated tau proteins, and neuronal loss in the brain of affected
      patients. The causes of neurodegeneration in AD are not clear, but apoptosis
      could be one of the cell death mechanisms. According to the amyloid hypothesis,
      abnormal aggregation of Abeta leads to altered kinase activities inducing tau
      phosphorylation and neuronal degeneration. Several studies have shown that pro
      apoptotic kinases could be a link between Abeta and tau anomalies. Here, we
      present recent evidences from AD experimental models and human studies that three
      pro-apoptotic kinases (double-stranded RNA kinase (PKR), glycogen synthase kinase
      3beta, and C-Jun terminal kinase (JNK) could be implicated in AD physiopathology.
      These kinases are detectable in human fluids and the analysis of their levels
      could be used as potential surrogate markers to evaluate cell death and clinical
      prognosis. In addition to current biomarkers (Abeta1-42, tau, and phosphorylated
      tau), these new evaluations could bring about valuable information on potential
      innovative therapeutic targets to alter the clinical evolution. 

PMID- 26300843
TI  - The Clinical Epidemiology of Spontaneous ICH in a Sub-Sahara African Country in
      the CT Scan Era: A Neurosurgical In-Hospital Cross-Sectional Survey.
AB  - BACKGROUND: There is paucity of data-driven scientific reports from sub-Saharan
      Africa on the burden of spontaneous intracerebral hemorrhage (sICH). We have
      maintained a prospective consecutive in-hospital database of cases of sICH
      referred for neurosurgical intervention over a 5-year period. METHODS: This is a
      cross-sectional descriptive study of the clinical epidemiology and brain computed
      tomography (CT) characterization of sICH from the database in this region in the
      current era. RESULTS: There were 63 subjects, 38 (60.3%) males, aged 28-85 years,
      mean 55.7 (SD, 12.7), the modal age distribution being the sixth decade.
      Uncontrolled hypertension was the main predisposition in the study: present,
      premorbid, in 79%, but uncontrolled in 88% of these known cases, and exhibited
      malignant derangements of blood pressure in more than half. The clinical ictus to
      in-hospital presentation was delayed, median 72 h; was in severe clinical state
      in 70%, 57% was comatose; and was complicated with fever in 57% and respiratory
      morbidity in 55.6%. The main clinical symptomatology was hemiparesis, headache,
      vomiting, and aphasia. The sICH was supratentorial on brain CT in 90.5%,
      ganglionic in 50.8%, and thalamic in 58.3% of the latter. The bleed had CT
      evidence of mass effect and intraventricular extension (IVH) in more than half.
      Twenty-three patients (36.5%) underwent operative interventions. CONCLUSION: In
      this patient population, sICH is mainly ganglionic and thalamic in location with
      significant rate of associated IVH. In-hospital clinical presentation is delayed,
      and in a critical state, the bleeding is uncontrolled hypertension related in
      >95%.

PMID- 26300844
TI  - Deep Brain Stimulation in Tourette's Syndrome.
AB  - OBJECTIVE: Tourette's syndrome (TS) is defined by 1 year of persistent motor and
      vocal tics. Often, the tics are refractory to conventional pharmacologic and
      psychobehavioral interventions. In these patients, deep brain stimulation (DBS)
      may be an appropriate intervention. This paper reviews different DBS targets in
      TS, discusses existing evidence on the efficacy of DBS in TS, highlights adverse
      effects of the procedure, discusses indications and patient selection as well as
      future directions for DBS in TS. METHODS: A literature review searching PubMed
      database entries between 2000 and 2015. Search terms included "DBS in Tourette
      Syndrome", "Deep brain stimulation in Tourette syndrome," and "Surgical
      management of Tourette Syndrome." RESULTS: Though there are no universally
      accepted guidelines defining ideal DBS candidates for TS, age, tic severity, and
      treatment refractoriness are important factors to consider in patient selection.
      A variety of targets exist for DBS in TS, but thalamic targets and GPi are the
      most widely studied. Psychiatric side effects that are target specific should be
      monitored closely and it is possible that these adverse effects may be resolved
      with programing. Small randomized controlled trials support the efficacy of DBS
      in TS. CONCLUSION: DBS for TS is safe and feasible, but large multi-center
      clinical trials are needed to determine the ideal target and optimal location
      within a particular target.

PMID- 26300845
TI  - Whole-Exome Sequencing in the Differential Diagnosis of Primary Adrenal
      Insufficiency in Children.
AB  - Adrenal insufficiency is a rare, but potentially fatal medical condition. In
      children, the cause is most commonly congenital and in recent years a growing
      number of causative gene mutations have been identified resulting in a myriad of
      syndromes that share adrenal insufficiency as one of the main characteristics.
      The evolution of adrenal insufficiency is dependent on the variant and the
      particular gene affected, meaning that rapid and accurate diagnosis is imperative
      for effective treatment of the patient. Common practice is for candidate genes to
      be sequenced individually, which is a time-consuming process and complicated by
      overlapping clinical phenotypes. However, with the availability, and increasing
      cost effectiveness of whole-exome sequencing, there is the potential for this to
      become a powerful diagnostic tool. Here, we report the results of whole-exome
      sequencing of 43 patients referred to us with a diagnosis of familial
      glucocorticoid deficiency (FGD) who were mutation negative for MC2R, MRAP, and
      STAR the most commonly mutated genes in FGD. WES provided a rapid genetic
      diagnosis in 17/43 sequenced patients, for the remaining 60% the gene defect may
      be within intronic/regulatory regions not covered by WES or may be in gene(s)
      representing novel etiologies. The diagnosis of isolated or familial
      glucocorticoid deficiency was only confirmed in 3 of the 17 patients, other
      genetic diagnoses were adrenal hypo- and hyperplasia, Triple A, and autoimmune
      polyendocrinopathy syndrome type I, emphasizing both the difficulty of
      phenotypically distinguishing between disorders of PAI and the utility of WES as
      a tool to achieve this. 

PMID- 26300846
TI  - Insights into Orphan Nuclear Receptors as Prognostic Markers and Novel
      Therapeutic Targets for Breast Cancer.
AB  - There is emerging evidence asserting the importance of orphan nuclear receptors
      (ONRs) in cancer initiation and progression. In breast cancer, there is a lot
      unknown about ONRs in terms of their expression profile and their transcriptional
      targets in the various stages of tumor progression. With the classification of
      breast tumors into distinct molecular subtypes, we assess ONR expression in the
      different breast cancer subtypes and with patient outcomes. Complementing this,
      we review evidence implicating ONR-dependent molecular pathways in breast cancer
      progression to identify candidate ONRs as potential prognostic markers and/or as
      therapeutic targets. 

PMID- 26300847
TI  - Chronic Oxytocin Administration as a Treatment Against Impaired Leptin Signaling
      or Leptin Resistance in Obesity.
AB  - This review summarizes the existing literature on the effects of oxytocin
      administration in the treatment of obesity in different animal models and in
      humans, focusing on the central control of food intake, the oxytocin effects on
      adipose tissue, and the relationships between oxytocin and leptin. Oxytocin is a
      hypothalamic nonapeptide synthesized mainly in the paraventricular and supraoptic
      nuclei projecting to the pituitary, where it reaches the peripheral circulation,
      as well as to other brain regions. Moreover, leptin modulates oxytocin levels and
      activates oxytocin neurons in the hypothalamic paraventricular nucleus, which
      innervates the nucleus of the solitary tract, partly responsible for the brain
      elicited oxytocin effects. Taking into account that oxytocin is located
      downstream leptin, it was hypothesized that oxytocin treatment would be effective
      in decreasing body weight in leptin-resistant DIO animals, as well as in those
      with leptin or with leptin receptor deficiency. Several groups have demonstrated
      that in such animal models (rats, mice, and rhesus monkeys), central or
      peripheral oxytocin administration decreases body weight, mainly due to a
      decrease in fat mass, demonstrating that an oxytocin treatment is able to partly
      overcome leptin deficiency or resistance. Moreover, a pilot clinical study
      demonstrated the efficiency of oxytocin in the treatment of obesity in human
      subjects, confirming the results obtained in the different animal models. Larger
      multicenter studies are now needed to determine whether the beneficial effects of
      oxytocin treatment can apply not only to obese but also to type 2 diabetic
      patients. These studies should also shed some light on the molecular mechanisms
      of oxytocin action in humans. 

PMID- 26300848
TI  - Pawnobiome: manipulation of the hologenome within one host generation and beyond.

PMID- 26300849
TI  - Pithovirus sibericum, a new bona fide member of the "Fourth TRUC" club.
AB  - Nucleocytoplasmic large DNA viruses, or representatives of the proposed order
      Megavirales, include giant viruses of Acanthamoeba that were discovered over the
      last 12 years and are bona fide microbes. Phylogenies based on a few genes
      conserved amongst these megaviruses and shared by microbes classified as Eukarya,
      Bacteria, and Archaea, allowed for delineation of a fourth monophylogenetic group
      or "TRUC" (Things Resisting Uncompleted Classification) composed of the
      Megavirales representatives. A new Megavirales member named Pithovirus sibericum
      was isolated from a >30,000-year-old dated Siberian permafrost sample. This
      virion is as large as recently described pandoraviruses but has a genome that is
      approximately three to four times shorter. Our objective was to update the
      classification of P. sibericum as a new member of the "Fourth TRUC" club.
      Phylogenetic trees were constructed based on four conserved ancient genes and a
      phyletic analysis was concurrently conducted based on the presence/absence
      patterns of a set of informational genes from members of Megavirales, Bacteria,
      Archaea, and Eukarya. Phylogenetic analyses based on the four conserved genes
      revealed that P. sibericum is part of the fourth TRUC composed of Megavirales
      members, and is closely related to the families Marseilleviridae and
      Ascoviridae/Iridoviridae. Additionally, hierarchical clustering delineated four
      branches, and showed that P. sibericum is part of this fourth TRUC. Overall,
      phylogenetic and phyletic analyses using informational genes clearly indicate
      that P. sibericum is a new bona fide member of the "Fourth TRUC" club composed of
      representatives of Megavirales, alongside Bacteria, Archaea, and Eukarya. 

PMID- 26300688
TI  - Search for heavy long-lived multi-charged particles in pp collisions at [Formula:
      see text] TeV using the ATLAS detector.
AB  - A search for heavy long-lived multi-charged particles is performed using the
      ATLAS detector at the LHC. Data collected in 2012 at [Formula: see text] TeV from
      pp collisions corresponding to an integrated luminosity of 20.3 fb[Formula: see
      text]are examined. Particles producing anomalously high ionisation, consistent
      with long-lived massive particles with electric charges from [Formula: see text]
      to [Formula: see text] are searched for. No signal candidate events are observed,
      and 95 % confidence level cross-section upper limits are interpreted as lower
      mass limits for a Drell-Yan production model. The mass limits range between 660
      and 785 GeV.

PMID- 26300852
TI  - Preliminary probiotic and technological characterization of Pediococcus
      pentosaceus strain KID7 and in vivo assessment of its cholesterol-lowering
      activity.
AB  - The study was aimed to characterize the probiotic properties of a Pediococcus
      pentosaceus strain, KID7, by in vitro and in vivo studies. The strain possessed
      tolerance to oro-gastrointestinal transit, adherence to the Caco-2 cell line, and
      antimicrobial activity. KID7 exhibited bile salt hydrolase activity and
      cholesterol-lowering activity, in vitro. In vivo cholesterol-lowering activity of
      KID7 was studied using atherogenic diet-fed hypercholesterolemic mice. The
      experimental animals (C57BL/6J mice) were divided into 4 groups viz., normal diet
      fed group (NCD), atherogenic diet-fed group (HCD), atherogenic diet- and KID7-fed
      group (HCD-KID7), and atherogenic diet- and Lactobacillus acidophilus ATCC 43121
      fed group (HCD-L.ac) as positive control. Serum total cholesterol (T-CHO) level
      was significantly decreased by 19.8% in the HCD-KID7 group (P < 0.05), but not in
      the HCD-L.ac group compared with the HCD group. LDL cholesterol levels in both
      HCD-KID7 and HCD-L.ac groups were decreased by 35.5 and 38.7%, respectively,
      compared with HCD group (both, P < 0.05). Glutamyl pyruvic transaminase (GPT)
      level was significantly lower in the HCD-KID7 and HCD-L.ac groups compared to HCD
      group and was equivalent to that of the NCD group. Liver T-CHO levels in the HCD
      KID7 group were reduced significantly compared with the HCD group (P < 0.05) but
      not in the HCD-L.ac group. Analysis of expression of genes associated with lipid
      metabolism in liver showed that low-density lipoprotein receptor (LDLR),
      cholesterol-7alpha-hydroxylase (CYP7A1) and apolipoprotein E (APOE) mRNA
      expression was significantly increase in the HCD-KID7 group compared to the HCD
      group. Furthermore, KID7 exhibited desired viability under freeze-drying and
      subsequent storage conditions with a combination of skim milk and galactomannan.
      P. pentosaceus KID7 could be a potential probiotic strain, which can be used to
      develop cholesterol-lowering functional food after appropriate human clinical
      trials. 

PMID- 26300851
TI  - Integrated inference and evaluation of host-fungi interaction networks.
AB  - Fungal microorganisms frequently lead to life-threatening infections. Within this
      group of pathogens, the commensal Candida albicans and the filamentous fungus
      Aspergillus fumigatus are by far the most important causes of invasive mycoses in
      Europe. A key capability for host invasion and immune response evasion are
      specific molecular interactions between the fungal pathogen and its human host.
      Experimentally validated knowledge about these crucial interactions is rare in
      literature and even specialized host-pathogen databases mainly focus on bacterial
      and viral interactions whereas information on fungi is still sparse. To establish
      large-scale host-fungi interaction networks on a systems biology scale, we
      develop an extended inference approach based on protein orthology and data on
      gene functions. Using human and yeast intraspecies networks as template, we
      derive a large network of pathogen-host interactions (PHI). Rigorous filtering
      and refinement steps based on cellular localization and pathogenicity information
      of predicted interactors yield a primary scaffold of fungi-human and fungi-mouse
      interaction networks. Specific enrichment of known pathogenicity-relevant genes
      indicates the biological relevance of the predicted PHI. A detailed inspection of
      functionally relevant subnetworks reveals novel host-fungal interaction
      candidates such as the Candida virulence factor PLB1 and the anti-fungal host
      protein APP. Our results demonstrate the applicability of interolog-based
      prediction methods for host-fungi interactions and underline the importance of
      filtering and refinement steps to attain biologically more relevant interactions.
      This integrated network framework can serve as a basis for future analyses of
      high-throughput host-fungi transcriptome and proteome data. 

PMID- 26300850
TI  - Beyond phage display: non-traditional applications of the filamentous
      bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation
      scaffold.
AB  - For the past 25 years, phage display technology has been an invaluable tool for
      studies of protein-protein interactions. However, the inherent biological,
      biochemical, and biophysical properties of filamentous bacteriophage, as well as
      the ease of its genetic manipulation, also make it an attractive platform outside
      the traditional phage display canon. This review will focus on the unique
      properties of the filamentous bacteriophage and highlight its diverse
      applications in current research. Particular emphases are placed on: (i) the
      advantages of the phage as a vaccine carrier, including its high immunogenicity,
      relative antigenic simplicity and ability to activate a range of immune
      responses, (ii) the phage's potential as a prophylactic and therapeutic agent for
      infectious and chronic diseases, (iii) the regularity of the virion major coat
      protein lattice, which enables a variety of bioconjugation and surface chemistry
      applications, particularly in nanomaterials, and (iv) the phage's large
      population sizes and fast generation times, which make it an excellent model
      system for directed protein evolution. Despite their ubiquity in the biosphere,
      metagenomics work is just beginning to explore the ecology of filamentous and non
      filamentous phage, and their role in the evolution of bacterial populations.
      Thus, the filamentous phage represents a robust, inexpensive, and versatile
      microorganism whose bioengineering applications continue to expand in new
      directions, although its limitations in some spheres impose obstacles to its
      widespread adoption and use. 

PMID- 26300853
TI  - Simple approach for the preparation of (15-15)N2-enriched water for nitrogen
      fixation assessments: evaluation, application and recommendations.
AB  - Recent findings revealed that the commonly used (15)N2 tracer assay for the
      determination of dinitrogen (N2) fixation can underestimate the activity of
      aquatic N2-fixing organisms. Therefore, a modification to the method using pre
      prepared (15-15)N2-enriched water was proposed. Here, we present a rigorous
      assessment and outline a simple procedure for the preparation of (15-15)N2
      enriched water. We recommend to fill sterile-filtered water into serum bottles
      and to add (15-15)N2 gas to the water in amounts exceeding the standard N2
      solubility, followed by vigorous agitation (vortex mixing >= 5 min). Optionally,
      water can be degassed at low-pressure (>=950 mbar) for 10 min prior to the (15
      15)N2 gas addition to indirectly enhance the (15-15)N2 concentration. This
      preparation of (15-15)N2-enriched water can be done within 1 h using standard
      laboratory equipment. The final (15)N-atom% excess was 5% after replacing 2-5% of
      the incubation volume with (15-15)N2-enriched water. Notably, the addition of (15
      15)N2-enriched water can alter levels of trace elements in the incubation water
      due to the contact of (15-15)N2-enriched water with glass, plastic and rubber
      ware. In our tests, levels of trace elements (Fe, P, Mn, Mo, Cu, Zn) increased by
      up to 0.1 nmol L(-1) in the final incubation volume, which may bias rate
      measurements in regions where N2 fixation is limited by trace elements. For these
      regions, we tested an alternative way to enrich water with (15-15)N2. The (15
      15)N2 was injected as a bubble directly to the incubation water, followed by
      gentle shaking. Immediately thereafter, the bubble was replaced with water to
      stop the (15-15)N2 equilibration. This approach achieved a (15)N-atom% excess of
      6.6 +/- 1.7% when adding 2 mL (15-15)N2 per liter of incubation water. The herein
      presented methodological tests offer guidelines for the (15)N2 tracer assay and
      thus, are crucial to circumvent methodological draw-backs for future N2 fixation
      assessments. 

PMID- 26300855
TI  - Impact of surface structure and feed gas composition on Bacillus subtilis
      endospore inactivation during direct plasma treatment.
AB  - This study investigated the inactivation efficiency of cold atmospheric pressure
      plasma treatment on Bacillus subtilis endospores dependent on the used feed gas
      composition and on the surface, the endospores were attached on. Glass petri
      dishes, glass beads, and peppercorns were inoculated with the same endospore
      density and treated with a radio frequency plasma jet. Generated reactive species
      were detected using optical emission spectroscopy. A quantitative polymerase
      chain reaction (qPCR) based ratio detection system was established to monitor the
      DNA damage during the plasma treatment. Argon + 0.135% vol. oxygen + 0.2% vol.
      nitrogen as feed gas emitted the highest amounts of UV-C photons and considerable
      amount of reactive oxygen and nitrogen species. Plasma generated with argon +
      0.135% vol. oxygen was characterized by the highest emission of reactive oxygen
      species (ROS), whereas the UV-C emission was negligible. The use of pure argon
      showed a negligible emission of UV photons and atomic oxygen, however, the
      emission of vacuum (V)UV photons was assumed. Similar maximum inactivation
      results were achieved for the three feed gas compositions. The surface structure
      had a significant impact on the inactivation efficiency of the plasma treatment.
      The maximum inactivation achieved was between 2.4 and 2.8 log10 on glass petri
      dishes and 3.9 to 4.6 log10 on glass beads. The treatment of peppercorns resulted
      in an inactivation lower than 1.0 log10. qPCR results showed a significant DNA
      damage for all gas compositions. Pure argon showed the highest results for the
      DNA damage ratio values, followed by argon + 0.135% vol. oxygen + 0.2% vol.
      nitrogen. In case of argon + 0.135% vol. oxygen the inactivation seems to be
      dominated by the action of ROS. These findings indicate the significant role of
      VUV and UV photons in the inactivation process of B. subtilis endospores. 

PMID- 26300857
TI  - Chemosensitization of multidrug resistant Candida albicans by the oxathiolone
      fused chalcone derivatives.
AB  - Three structurally related oxathiolone fused chalcone derivatives appeared
      effective chemosensitizers, able to restore in part sensitivity to fluconazole of
      multidrug-resistant C. albicans strains. Compound 21 effectively chemosensitized
      cells resistant due to the overexpression of the MDR1 gene, compound 6 reduced
      resistance of cells overexpressing the ABC-type drug transporters CDR1/CDR2 and
      derivative 18 partially reversed fluconazole resistance mediated by both types of
      yeast drug efflux pumps. The observed effect of sensitization of resistant
      strains of Candida albicans to fluconazole activity in the presence of active
      compounds most likely resulted from inhibition of the pump-mediated efflux, as
      was revealed by the results of studies involving the fluorescent probes, Nile
      Red, Rhodamine 6G and diS-C3(3). 

PMID- 26300856
TI  - Equol status and changes in fecal microbiota in menopausal women receiving long
      term treatment for menopause symptoms with a soy-isoflavone concentrate.
AB  - The knowledge regarding the intestinal microbial types involved in isoflavone
      bioavailability and metabolism is still limited. The present work reports the
      influence of a treatment with isoflavones for 6 months on the fecal bacterial
      communities of 16 menopausal women, as determined by culturing and culture
      independent microbial techniques. Changes in fecal communities were analyzed with
      respect to the women's equol-producing phenotype. Compared to baseline, at 1 and
      3 months the counts for all microbial populations in the feces of equol-producing
      women had increased strongly. In contrast, among the non-producers, the counts
      for all microbial populations at 1 month were similar to those at baseline, and
      decreased significantly by 3 and 6 months. Following isoflavone intake, major
      bands in the denaturing gradient gel electrophoresis (DGGE) profiles appeared and
      disappeared, suggesting important changes in majority populations. In some women,
      increases were seen in the intensity of specific DGGE bands corresponding to
      microorganisms known to be involved in the metabolism of dietary phytoestrogens
      (Lactonifactor longoviformis, Faecalibacterium prausnitzii, Bifidobacterium sp.,
      Ruminococcus sp.). Real-Time quantitative PCR revealed that the Clostridium
      leptum and C. coccoides populations increased in equol producers, while those of
      bifidobacteria and enterobacteria decreased, and vice versa in the non-producers.
      Finally, the Atopobium population increased in both groups, but especially in the
      non-producers at three months. As the main findings of this study, (i) variations
      in the microbial communities over the 6-month period of isoflavone
      supplementation were large; (ii) no changes in the fecal microbial populations
      that were convincingly treatment-specific were seen; and (iii) the production of
      equol did not appear to be associated with the presence of, or increase in the
      population of, any of the majority bacterial types analyzed. 

PMID- 26300858
TI  - Rapid detection of porins by matrix-assisted laser desorption/ionization-time of
      flight mass spectrometry.
AB  - The rapid and cost-efficient determination of carbapenem resistance is an
      important prerequisite for the choice of an adequate antibiotic therapy. A MALDI
      TOF MS-based assay was set up to detect porins in the current study. A loss of
      the components of porin alone such as OmpK35/OmpK36 or together with the
      production of carbapenemases will augment the carbapenem resistance. Ten strains
      of Escherichia coli and eight strains of Klebsiella pneumoniae were conducted for
      both sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and
      MALDI-TOF MS analysis. MALDI-TOF/TOF MS analysis was then performed to verify the
      correspondence of proteins between SDS-PAGE and MALDI-TOF MS. The results
      indicated that the mass spectrum of ca. 35,000, 37,000, and 38,000-m/z peaks of
      E. coli ATCC 25922 corresponded to OmpA, OmpC, and OmpF with molecular weight of
      approximately ca. 38, 40, and 41 kDa in SDS-PAGE gel, respectively. The band of
      OmpC and OmpF porins were unable to be distinguished by SDS-PAGE, whereas it was
      easy to be differentiated by MALDI-TOF MS. As for K. pneumoniae isolates, the
      mass spectrum of ca. 36,000 and 38,600-m/z peaks was observed corresponding to
      OmpA and OmpK36 with molecular weight of approximately ca. 40 and 42 kDa in SDS
      PAGE gel, respectively. Porin OmpK35 was not observed in the current SDS-PAGE,
      while a 37,000-m/z peak was found in K. pneumoniae ATCC 13883 and carbapenem
      susceptible strains by MALDI-TOF MS which was presumed to be the characteristic
      peak of the OmpK35 porin. Compared with SDS-PAGE, MALDI-TOF MS is able to rapidly
      identify the porin-deficient strains within half an hour with better sensitivity,
      less cost, and is easier to operate and has less interference. 

PMID- 26300854
TI  - Primer and platform effects on 16S rRNA tag sequencing.
AB  - Sequencing of 16S rRNA gene tags is a popular method for profiling and comparing
      microbial communities. The protocols and methods used, however, vary considerably
      with regard to amplification primers, sequencing primers, sequencing
      technologies; as well as quality filtering and clustering. How results are
      affected by these choices, and whether data produced with different protocols can
      be meaningfully compared, is often unknown. Here we compare results obtained
      using three different amplification primer sets (targeting V4, V6-V8, and V7-V8)
      and two sequencing technologies (454 pyrosequencing and Illumina MiSeq) using DNA
      from a mock community containing a known number of species as well as complex
      environmental samples whose PCR-independent profiles were estimated using shotgun
      sequencing. We find that paired-end MiSeq reads produce higher quality data and
      enabled the use of more aggressive quality control parameters over 454, resulting
      in a higher retention rate of high quality reads for downstream data analysis.
      While primer choice considerably influences quantitative abundance estimations,
      sequencing platform has relatively minor effects when matched primers are used.
      Beta diversity metrics are surprisingly robust to both primer and sequencing
      platform biases. 

PMID- 26300859
TI  - Regulation of biofilm formation by BpfA, BpfD, and BpfG in Shewanella oneidensis.
AB  - Bacteria switch between two distinct life styles - planktonic (free living) and
      biofilm forming - in keeping with their ever-changing environment. Such switch
      involves sophisticated signaling and tight regulation, which provides a
      fascinating portal for studying gene function and orchestrated protein
      interactions. In this work, we investigated the molecular mechanism underlying
      biofilm formation in Shewanella oneidensis MR-1, an environmentally important
      model bacterium renowned for respiratory diversities, and uncovered a gene
      cluster coding for seven proteins involved in this process. The three key
      proteins, BpfA, BpfG, and BpfD, were studied in detail for the first time. BpfA
      directly participates in biofilm formation as extracellular "glue" BpfG is not
      only indispensable for BpfA export during biofilm forming but also functions to
      turn BpfA into active form for biofilm dispersing. BpfD regulates biofilm
      development by interacting with both BpfA and BpfG, likely in response to signal
      molecule c-di-GMP. In addition, we found that 1:1 stoichiometry between BpfD and
      BpfG is critical for biofilm formation. Furthermore, we demonstrated that a
      biofilm over-producing phenotype can be induced by C116S mutation but not loss of
      BpfG. 

PMID- 26300861
TI  - Distinct stages during colonization of the mouse gastrointestinal tract by
      Candida albicans.
AB  - Candida albicans is a member of the human microbiota, colonizing both the vaginal
      and gastrointestinal tracts. This yeast is devoid of a life style outside the
      human body and the mechanisms underlying the adaptation to the commensal status
      remain to be determined. Using a model of mouse gastrointestinal colonization, we
      show here that C. albicans stably colonizes the mouse gut in about 3 days
      starting from a dose as low as 100 cells, reaching steady levels of around 10(7)
      cells/g of stools. Using fluorescently labeled strains, we have assessed the
      competition between isogenic populations from different sources in cohoused
      animals. We show that long term (15 days) colonizing cells have increased fitness
      in the gut niche over those grown in vitro or residing in the gut for 1-3 days.
      Therefore, two distinct states, proliferation and adaptation, seem to exist in
      the adaptation of this fungus to the mouse gut, a result with potential
      significance in the prophylaxis and treatment of Candida infections. 

PMID- 26300863
TI  - Transcriptome analysis of Enterococcus faecalis in response to alkaline stress.
AB  - Enterococcus faecalis is the most commonly isolated species from endodontic
      failure root canals; its persistence in treated root canals has been attributed
      to its ability to resist high pH stress. The goal of this study was to
      characterize the E. faecalis transcriptome and to identify candidate genes for
      response and resistance to alkaline stress using Illumina HiSeq 2000 sequencing.
      We found that E. faecalis could survive and form biofilms in a pH 10 environment
      and that alkaline stress had a great impact on the transcription of many genes in
      the E. faecalis genome. The transcriptome sequencing results revealed that 613
      genes were differentially expressed (DEGs) for E. faecalis grown in pH 10 medium;
      211 genes were found to be differentially up-regulated and 402 genes
      differentially down-regulated. Many of the down-regulated genes found are
      involved in cell energy production and metabolism and carbohydrate and amino acid
      metabolism, and the up-regulated genes are mostly related to nucleotide transport
      and metabolism. The results presented here reveal that cultivation of E. faecalis
      in alkaline stress has a profound impact on its transcriptome. The observed
      regulation of genes and pathways revealed that E. faecalis reduced its
      carbohydrate and amino acid metabolism and increased nucleotide synthesis to
      adapt and grow in alkaline stress. A number of the regulated genes may be useful
      candidates for the development of new therapeutic approaches for the treatment of
      E. faecalis infections. 

PMID- 26300862
TI  - Coxiella burnetii and Leishmania mexicana residing within similar parasitophorous
      vacuoles elicit disparate host responses.
AB  - Coxiella burnetii is a bacterium that thrives in an acidic parasitophorous
      vacuole (PV) derived from lysosomes. Leishmania mexicana, a eukaryote, has also
      independently evolved to live in a morphologically similar PV. As Coxiella and
      Leishmania are highly divergent organisms that cause different diseases, we
      reasoned that their respective infections would likely elicit distinct host
      responses despite producing phenotypically similar parasite-containing vacuoles.
      The objective of this study was to investigate, at the molecular level, the
      macrophage response to each pathogen. Infection of THP-1 (human
      monocyte/macrophage) cells with Coxiella and Leishmania elicited disparate host
      responses. At 5 days post-infection, when compared to uninfected cells, 1057
      genes were differentially expressed (746 genes up-regulated and 311 genes down
      regulated) in C. burnetii infected cells, whereas 698 genes (534 genes up
      regulated and 164 genes down-regulated) were differentially expressed in L.
      mexicana infected cells. Interestingly, of the 1755 differentially expressed
      genes identified in this study, only 126 genes (~7%) are common to both
      infections. We also discovered that 1090 genes produced mRNA isoforms at
      significantly different levels under the two infection conditions, suggesting
      that alternate proteins encoded by the same gene might have important roles in
      host response to each infection. Additionally, we detected 257 micro RNAs
      (miRNAs) that were expressed in THP-1 cells, and identified miRNAs that were
      specifically expressed during Coxiella or Leishmania infections. Collectively,
      this study identified host mRNAs and miRNAs that were influenced by Coxiella
      and/or Leishmania infections, and our data indicate that although their PVs are
      morphologically similar, Coxiella and Leishmania have evolved different
      strategies that perturb distinct host processes to create and thrive within their
      respective intracellular niches. 

PMID- 26300860
TI  - MALDI-TOF mass spectrometry: an emerging technology for microbial identification
      and diagnosis.
AB  - Currently microorganisms are best identified using 16S rRNA and 18S rRNA gene
      sequencing. However, in recent years matrix assisted laser desorption ionization
      time of flight mass spectrometry (MALDI-TOF MS) has emerged as a potential tool
      for microbial identification and diagnosis. During the MALDI-TOF MS process,
      microbes are identified using either intact cells or cell extracts. The process
      is rapid, sensitive, and economical in terms of both labor and costs involved.
      The technology has been readily imbibed by microbiologists who have reported
      usage of MALDI-TOF MS for a number of purposes like, microbial identification and
      strain typing, epidemiological studies, detection of biological warfare agents,
      detection of water- and food-borne pathogens, detection of antibiotic resistance
      and detection of blood and urinary tract pathogens etc. The limitation of the
      technology is that identification of new isolates is possible only if the
      spectral database contains peptide mass fingerprints of the type strains of
      specific genera/species/subspecies/strains. This review provides an overview of
      the status and recent applications of mass spectrometry for microbial
      identification. It also explores the usefulness of this exciting new technology
      for diagnosis of diseases caused by bacteria, viruses, and fungi. 

PMID- 26300864
TI  - Sulfonamide and tetracycline resistance genes in total- and culturable-bacterial
      assemblages in South African aquatic environments.
AB  - Antibiotic resistant bacteria are ubiquitous in the natural environment. The
      introduction of effluent derived antibiotic resistance genes (ARGs) into aquatic
      environments is of concern in the spreading of genetic risk. This study showed
      the prevalence of sulfonamide and tetracycline resistance genes, sul1, sul2,
      sul3, and tet(M), in the total bacterial assemblage and colony forming bacterial
      assemblage in river and estuarine water and sewage treatment plants (STP) in
      South Africa. There was no correlation between antibiotic concentrations and
      ARGs, suggesting the targeted ARGs are spread in a wide area without connection
      to selection pressure. Among sul genes, sul1 and sul2 were major genes in the
      total (over 10(-2) copies/16S) and colony forming bacteria assemblages (~10(-1)
      copies/16S). In urban waters, the sul3 gene was mostly not detectable in total
      and culturable assemblages, suggesting sul3 is not abundant. tet(M) was found in
      natural assemblages with 10(-3) copies/16S level in STP, but was not detected in
      colony forming bacteria, suggesting the non-culturable (yet-to-be cultured)
      bacterial community in urban surface waters and STP effluent possess the tet(M)
      gene. Sulfamethoxazole (SMX) resistant (SMX(r)) and oxytetracycline (OTC)
      resistant (OTC(r)) bacterial communities in urban waters possessed not only sul1
      and sul2 but also sul3 and tet(M) genes. These genes are widely distributed in
      SMX(r) and OTC(r) bacteria. In conclusion, urban river and estuarine water and
      STP effluent in the Durban area were highly contaminated with ARGs, and the yet
      to-be cultured bacterial community may act as a non-visible ARG reservoir in
      certain situations. 

PMID- 26300865
TI  - Metagenome-based diversity analyses suggest a significant contribution of non
      cyanobacterial lineages to carbonate precipitation in modern microbialites.
AB  - Cyanobacteria are thought to play a key role in carbonate formation due to their
      metabolic activity, but other organisms carrying out oxygenic photosynthesis
      (photosynthetic eukaryotes) or other metabolisms (e.g., anoxygenic
      photosynthesis, sulfate reduction), may also contribute to carbonate formation.
      To obtain more quantitative information than that provided by more classical PCR
      dependent methods, we studied the microbial diversity of microbialites from the
      Alchichica crater lake (Mexico) by mining for 16S/18S rRNA genes in metagenomes
      obtained by direct sequencing of environmental DNA. We studied samples collected
      at the Western (AL-W) and Northern (AL-N) shores of the lake and, at the latter
      site, along a depth gradient (1, 5, 10, and 15 m depth). The associated microbial
      communities were mainly composed of bacteria, most of which seemed heterotrophic,
      whereas archaea were negligible. Eukaryotes composed a relatively minor fraction
      dominated by photosynthetic lineages, diatoms in AL-W, influenced by Si-rich
      seepage waters, and green algae in AL-N samples. Members of the
      Gammaproteobacteria and Alphaproteobacteria classes of Proteobacteria,
      Cyanobacteria, and Bacteroidetes were the most abundant bacterial taxa, followed
      by Planctomycetes, Deltaproteobacteria (Proteobacteria), Verrucomicrobia,
      Actinobacteria, Firmicutes, and Chloroflexi. Community composition varied among
      sites and with depth. Although cyanobacteria were the most important bacterial
      group contributing to the carbonate precipitation potential, photosynthetic
      eukaryotes, anoxygenic photosynthesizers and sulfate reducers were also very
      abundant. Cyanobacteria affiliated to Pleurocapsales largely increased with
      depth. Scanning electron microscopy (SEM) observations showed considerable areas
      of aragonite-encrusted Pleurocapsa-like cyanobacteria at microscale. Multivariate
      statistical analyses showed a strong positive correlation of Pleurocapsales and
      Chroococcales with aragonite formation at macroscale, and suggest a potential
      causal link. Despite the previous identification of intracellularly calcifying
      cyanobacteria in Alchichica microbialites, most carbonate precipitation seems
      extracellular in this system. 

PMID- 26300866
TI  - Albendazole induces oxidative stress and DNA damage in the parasitic protozoan
      Giardia duodenalis.
AB  - The control of Giardia duodenalis infections is carried out mainly by drugs,
      among these albendazole (ABZ) is commonly used. Although the cytotoxic effect of
      ABZ usually involves binding to beta-tubulin, it has been suggested that
      oxidative stress may also play a role in its parasiticidal mechanism. In this
      work the effect of ABZ in Giardia clones that are susceptible or resistant to
      different concentrations (1.35, 8, and 250 MUM) of this drug was analyzed.
      Reactive oxygen species (ROS) were induced by ABZ in susceptible clones and this
      was associated with a decrease in growth that was alleviated by cysteine
      supplementation. Remarkably, ABZ-resistant clones exhibited partial cross
      resistance to H2O2, whereas a Giardia H2O2-resistant strain can grow in the
      presence of ABZ. Lipid oxidation and protein carbonylation in ABZ-treated
      parasites did not show significant differences as compared to untreated
      parasites; however, ABZ induced the formation of 8OHdG adducts and DNA
      degradation, indicating nucleic acid oxidative damage. This was supported by
      observations of histone H2AX phosphorylation in ABZ-susceptible trophozoites
      treated with 250 MUM ABZ. Flow cytometry analysis showed that ABZ partially
      arrested cell cycle in drug-susceptible clones at G2/M phase at the expense of
      cells in G1 phase. Also, ABZ treatment resulted in phosphatidylserine exposure on
      the parasite surface, an event related to apoptosis. All together these data
      suggest that ROS induced by ABZ affect Giardia genetic material through oxidative
      stress mechanisms and subsequent induction of apoptotic-like events. 

PMID- 26300867
TI  - Chronic widespread dermatophytosis due to Trichophyton rubrum: a syndrome
      associated with a Trichophyton-specific functional defect of phagocytes.
AB  - Dermatophytes are agents of typically benign superficial infections. However, an
      increasing number of severe infections in immunocompromised hosts has been
      reported. We aimed to understand the factors underlying the existence of a cohort
      of patients presenting with chronic widespread dermatophytosis (CWD) due to
      Trichophyton rubrum, but with no signs of immunodeficiency. Their disease is
      usually recurrent and difficult to manage. Fourteen patients meeting the
      following criteria for CWD were studied: T. rubrum culture-proven skin lesions of
      >=10 cm in at least one dimension; the involvement of at least three non
      contiguous localizations of >1 year's duration; and no predisposing conditions.
      For comparison, we also studied 13 acute Tinea pedis patients. Macrophages and
      neutrophils were isolated and tested for T. rubrum conidia phagocytic and killing
      activity. H2O2, NO, and pro- and anti-inflammatory cytokine release were
      measured. All experiments were run with age- and sex-matched healthy donors'
      cells in parallel. CWD patients' macrophages and neutrophils presented with
      reduced T. rubrum-phagocytic and killing abilities, and reduced H2O2 and NO
      release when compared with those of healthy donors. CWD patients' macrophages
      secreted lower levels of the proinflammatory cytokines interleukin (IL)-1beta, IL
      6, IL-8, and tumor necrosis factor (TNF)-alpha, but enhanced levels of the anti
      inflammatory cytokine IL-10. Neutrophil secretion closely followed this
      unbalanced pattern. In contrast, responses to the positive controls zymosan,
      lipopolysaccharide, and phorbol myristate acetate were comparable with those of
      healthy donors. The same experiments were performed with macrophages and
      neutrophils from the acute Tinea pedis patients and showed no differences when
      compared with the matched healthy donors. Patients with CWD have a T. rubrum
      related functional deficiency of phagocytes and may represent a distinct clinical
      entity in the complex spectrum of the Trichophyton-host interaction. 

PMID- 26300868
TI  - Is the lower atmosphere a readily accessible reservoir of culturable,
      antimicrobial compound-producing Actinomycetales?
AB  - Recent metagenomic studies have revealed that microbial diversity in the
      atmosphere rivals that of surface environments. This indicates that the
      atmosphere may be worth bioprospecting in for novel microorganisms, especially
      those selected for by harsh atmospheric conditions. This is interesting in light
      of the antibiotic resistance crisis and renewed interests in bioprospecting for
      members of the Actinomycetales, which harbor novel secondary metabolite-producing
      pathways and produce spores that make them well suited for atmospheric travel.
      The latter leads to the hypothesis that the atmosphere may be a promising
      environment in which to search for novel Actinomycetales. Although ubiquitous in
      soils, where bioprospecting efforts for Actinomycetales have been and are largely
      still focused, we present novel data indicating that culturable members of this
      taxonomic order are 3-5.6 times more abundant in air samples collected at 1.5,
      4.5, 7.5, and 18 m above the ground, than in the underlying soil. These results
      support the hypothesis that mining the vast and readily accessible lower
      atmosphere for novel Actinomycetales in the search for undescribed secondary
      metabolites could prove fruitful. 

PMID- 26300869
TI  - Potential impacts of aquatic pollutants: sub-clinical antibiotic concentrations
      induce genome changes and promote antibiotic resistance.
AB  - Antibiotics are disseminated into aquatic environments via human waste streams
      and agricultural run-off. Here they can persist at low, but biologically
      relevant, concentrations. Antibiotic pollution establishes a selection gradient
      for resistance and may also raise the frequency of events that generate
      resistance: point mutations; recombination; and lateral gene transfer. This study
      examined the response of bacteria to sub-inhibitory levels of antibiotics.
      Pseudomonas aeruginosa and Pseudomonas protegens were exposed kanamycin,
      tetracycline or ciprofloxacin at 1/10 the minimal inhibitory concentration (MIC)
      in a serial streaking experiment over 40 passages. Significant changes in rep-PCR
      fingerprints were noted in both species when exposed to sub-inhibitory antibiotic
      concentrations. These changes were observed in as few as five passages, despite
      the fact that the protocols used sample less than 0.3% of the genome, in turn
      suggesting much more widespread alterations to sequence and genome architecture.
      Experimental lines also displayed variant colony morphologies. The final MICs
      were significantly higher in some experimental lineages of P. protegens,
      suggesting that 1/10 the MIC induces de-novo mutation events that generate
      resistance phenotypes. The implications of these results are clear: exposure of
      the environmental microbiome to antibiotic pollution will induce similar changes,
      including generating newly resistant species that may be of significant concern
      for human health. 

PMID- 26300870
TI  - IFN-beta-inducing, unusual viral RNA species produced by paramyxovirus infection
      accumulated into distinct cytoplasmic structures in an RNA-type-dependent manner.
AB  - The interferon (IFN) system is one of the most important defensive responses of
      mammals against viruses, and is rapidly evoked when the pathogen-associated
      molecular patterns (PAMPs) of viruses are sensed. Non-self, virus-derived RNA
      species have been identified as the PAMPs of RNA viruses. In the present study,
      we compared different types of IFN-beta-inducing and -non-inducing viruses in the
      context of Sendai virus infection. We found that some types of unusual viral RNA
      species were produced by infections with IFN-beta-inducing viruses and
      accumulated into distinct cytoplasmic structures in an RNA-type-dependent manner.
      One of these structures was similar to the so-called antiviral stress granules
      (avSGs) formed by an infection with IFN-inducing viruses whose C proteins were
      knocked-out or mutated. Non-encapsidated, unusual viral RNA harboring the 5'
      terminal region of the viral genome as well as RIG-I and typical SG markers
      accumulated in these granules. Another was a non-SG-like inclusion formed by an
      infection with the Cantell strain; a copyback-type DI genome, but not an
      authentic viral genome, specifically accumulated in the inclusion, whereas RIG-I
      and SG markers did not. The induction of IFN-beta was closely associated with the
      production of these unusual RNAs as well as the formation of the cytoplasmic
      structures. 

PMID- 26300872
TI  - Analysis of the Bacillus cereus SpoIIS antitoxin-toxin system reveals its three
      component nature.
AB  - Programmed cell death in bacteria is generally associated with two-component
      toxin-antitoxin systems. The SpoIIS toxin-antitoxin system, consisting of a
      membrane-bound SpoIISA toxin and a small, cytosolic antitoxin SpoIISB, was
      originally identified in Bacillus subtilis. In this work we describe the Bacillus
      cereus SpoIIS system which is a three-component system, harboring an additional
      gene spoIISC. Its protein product serves as an antitoxin, and similarly as
      SpoIISB, is able to bind SpoIISA and abolish its toxic effect. Our results
      indicate that SpoIISC seems to be present not only in B. cereus but also in other
      Bacilli containing a SpoIIS toxin-antitoxin system. In addition, we show that B.
      cereus SpoIISA can form higher oligomers and we discuss the possible role of this
      multimerization for the protein's toxic function. 

PMID- 26300871
TI  - The two-component system CpxR/A represses the expression of Salmonella virulence
      genes by affecting the stability of the transcriptional regulator HilD.
AB  - Salmonella enterica can cause intestinal or systemic infections in humans and
      animals mainly by the presence of pathogenicity islands SPI-1 and SPI-2,
      containing 39 and 44 genes, respectively. The AraC-like regulator HilD positively
      controls the expression of the SPI-1 genes, as well as many other Salmonella
      virulence genes including those located in SPI-2. A previous report indicates
      that the two-component system CpxR/A regulates the SPI-1 genes: the absence of
      the sensor kinase CpxA, but not the absence of its cognate response regulator
      CpxR, reduces their expression. The presence and absence of cell envelope stress
      activates kinase and phosphatase activities of CpxA, respectively, which in turn
      controls the level of phosphorylated CpxR (CpxR-P). In this work, we further
      define the mechanism for the CpxR/A-mediated regulation of SPI-1 genes. The
      negative effect exerted by the absence of CpxA on the expression of SPI-1 genes
      was counteracted by the absence of CpxR or by the absence of the two enzymes,
      AckA and Pta, which render acetyl-phosphate that phosphorylates CpxR.
      Furthermore, overexpression of the lipoprotein NlpE, which activates CpxA kinase
      activity on CpxR, or overexpression of CpxR, repressed the expression of SPI-1
      genes. Thus, our results provide several lines of evidence strongly supporting
      that the absence of CpxA leads to the phosphorylation of CpxR via the AckA/Pta
      enzymes, which represses both the SPI-1 and SPI-2 genes. Additionally, we show
      that in the absence of the Lon protease, which degrades HilD, the CpxR-P-mediated
      repression of the SPI-1 genes is mostly lost; moreover, we demonstrate that CpxR
      P negatively affects the stability of HilD and thus decreases the expression of
      HilD-target genes, such as hilD itself and hilA, located in SPI-1. Our data
      further expand the insight on the different regulatory pathways for gene
      expression involving CpxR/A and on the complex regulatory network governing
      virulence in Salmonella. 

PMID- 26300873
TI  - Editorial: Breaking the cycle: attacking the malaria parasite in the liver.

PMID- 26300874
TI  - Comparative genomic analysis of multiple strains of two unusual plant pathogens:
      Pseudomonas corrugata and Pseudomonas mediterranea.
AB  - The non-fluorescent pseudomonads, Pseudomonas corrugata (Pcor) and P.
      mediterranea (Pmed), are closely related species that cause pith necrosis, a
      disease of tomato that causes severe crop losses. However, they also show strong
      antagonistic effects against economically important pathogens, demonstrating
      their potential for utilization as biological control agents. In addition, their
      metabolic versatility makes them attractive for the production of commercial
      biomolecules and bioremediation. An extensive comparative genomics study is
      required to dissect the mechanisms that Pcor and Pmed employ to cause disease,
      prevent disease caused by other pathogens, and to mine their genomes for genes
      that encode proteins involved in commercially important chemical pathways. Here,
      we present the draft genomes of nine Pcor and Pmed strains from different
      geographical locations. This analysis covered significant genetic heterogeneity
      and allowed in-depth genomic comparison. All examined strains were able to
      trigger symptoms in tomato plants but not all induced a hypersensitive-like
      response in Nicotiana benthamiana. Genome-mining revealed the absence of type III
      secretion system and known type III effector-encoding genes from all examined
      Pcor and Pmed strains. The lack of a type III secretion system appears to be
      unique among the plant pathogenic pseudomonads. Several gene clusters coding for
      type VI secretion system were detected in all genomes. Genome-mining also
      revealed the presence of gene clusters for biosynthesis of siderophores,
      polyketides, non-ribosomal peptides, and hydrogen cyanide. A highly conserved
      quorum sensing system was detected in all strains, although species specific
      differences were observed. Our study provides the basis for in-depth
      investigations regarding the molecular mechanisms underlying virulence strategies
      in the battle between plants and microbes. 

PMID- 26300875
TI  - The application of tetracyclineregulated gene expression systems in the
      validation of novel drug targets in Mycobacterium tuberculosis.
AB  - Although efforts to identify novel therapies for the treatment of tuberculosis
      have led to the identification of several promising drug candidates, the
      identification of high-quality hits from conventional whole-cell screens remains
      disappointingly low. The elucidation of the genome sequence of Mycobacterium
      tuberculosis (Mtb) facilitated a shift to target-based approaches to drug design
      but these efforts have proven largely unsuccessful. More recently, regulated gene
      expression systems that enable dose-dependent modulation of gene expression have
      been applied in target validation to evaluate the requirement of individual genes
      for the growth of Mtb both in vitro and in vivo. Notably, these systems can also
      provide a measure of the extent to which putative targets must be depleted in
      order to manifest a growth inhibitory phenotype. Additionally, the successful
      implementation of Mtb strains engineered to under-express specific molecular
      targets in whole-cell screens has enabled the simultaneous identification of cell
      permeant inhibitors with defined mechanisms of action. Here, we review the
      application of tetracycline-regulated gene expression systems in the validation
      of novel drug targets in Mtb, highlighting both the strengths and limitations
      associated with this approach to target validation. 

PMID- 26300877
TI  - Evolution of cyclizing 5-aminolevulinate synthases in the biosynthesis of
      actinomycete secondary metabolites: outcomes for genetic screening techniques.
AB  - A combined approach, comprising PCR screening and genome mining, was used to
      unravel the diversity and phylogeny of genes encoding 5-aminolevulinic acid
      synthases (ALASs, hemA gene products) in streptomycetes-related strains. In
      actinomycetes, these genes were believed to be directly connected with the
      production of secondary metabolites carrying the C5N unit, 2-amino-3
      hydroxycyclopent-2-enone, with biological activities making them attractive for
      future use in medicine and agriculture. Unlike "classical" primary metabolism
      ALAS, the C5N unit-forming cyclizing ALAS (cALAS) catalyses intramolecular
      cyclization of nascent 5-aminolevulinate. Specific amino acid sequence changes
      can be traced by comparison of "classical" ALASs against cALASs. PCR screening
      revealed 226 hemA gene-carrying strains from 1,500 tested, with 87% putatively
      encoding cALAS. Phylogenetic analysis of the hemA homologs revealed strain
      clustering according to putative type of metabolic product, which could be used
      to select producers of specific C5N compound classes. Supporting information was
      acquired through analysis of actinomycete genomic sequence data available in
      GenBank and further genetic or metabolic characterization of selected strains.
      Comparison of 16S rRNA taxonomic identification and BOX-PCR profiles provided
      evidence for numerous horizontal gene transfers of biosynthetic genes or gene
      clusters within actinomycete populations and even from non-actinomycete
      organisms. Our results underline the importance of environmental and evolutionary
      data in the design of efficient techniques for identification of novel producers.

PMID- 26300878
TI  - Efflux-mediated resistance to a benzothiadiazol derivative effective against
      Burkholderia cenocepacia.
AB  - Burkholderia cenocepacia is a major concern for people suffering from cystic
      fibrosis as it contributes to serious respiratory tract infections. The lack of
      drugs effective against this opportunistic pathogen, along with the high level of
      resistance to multiple antibiotics, render the treatment of these infections
      particularly difficult. Here a new compound, belonging to the 2,1,3
      benzothiadiazol-5-yl family (10126109), with a bactericidal effect and a minimal
      inhibitory concentration (MIC) of 8 MUg/ml against B. cenocepacia, is described.
      The compound is not cytotoxic and effective against B. cenocepacia clinical
      isolates and members of all the known B. cepacia complex species. Spontaneous
      mutants resistant to 10126109 were isolated and mutations in the MerR
      transcriptional regulator BCAM1948 were identified. In this way, a mechanism of
      resistance to this new molecule was described, which relies on the overexpression
      of the RND-9 efflux pump. Indeed, rnd-9 overexpression was confirmed by
      quantitative reverse transcription PCR, and RND-9 was identified in the membrane
      fractions of the mutant strains. Moreover, the increase in the MIC values of
      different drugs in the mutant strains, together with complementation experiments,
      suggested the involvement of RND-9 in the efflux of 10126109, thus indicating
      again the central role of efflux transporters in B. cenocepacia drug resistance. 

PMID- 26300876
TI  - Role of fatty acids in Bacillus environmental adaptation.
AB  - The large bacterial genus Bacillus is widely distributed in the environment and
      is able to colonize highly diverse niches. Some Bacillus species harbor
      pathogenic characteristics. The fatty acid (FA) composition is among the
      essential criteria used to define Bacillus species. Some elements of the FA
      pattern composition are common to Bacillus species, whereas others are specific
      and can be categorized in relation to the ecological niches of the species.
      Bacillus species are able to modify their FA patterns to adapt to a wide range of
      environmental changes, including changes in the growth medium, temperature, food
      processing conditions, and pH. Like many other Gram-positive bacteria, Bacillus
      strains display a well-defined FA synthesis II system that is equilibrated with a
      FA degradation pathway and regulated to efficiently respond to the needs of the
      cell. Like endogenous FAs, exogenous FAs may positively or negatively affect the
      survival of Bacillus vegetative cells and the spore germination ability in a
      given environment. Some of these exogenous FAs may provide a powerful strategy
      for preserving food against contamination by the Bacillus pathogenic strains
      responsible for foodborne illness. 

PMID- 26300879
TI  - Thoughts on a very acidic symbiosome.

PMID- 26300880
TI  - Immune Tolerance Maintained by Cooperative Interactions between T Cells and
      Antigen Presenting Cells Shapes a Diverse TCR Repertoire.
AB  - The T cell population in an individual needs to avoid harmful activation by self
      peptides while maintaining the ability to respond to an unknown set of foreign
      peptides. This property is acquired by a combination of thymic and extra-thymic
      mechanisms. We extend current models for the development of self/non-self
      discrimination to consider the acquisition of self-tolerance as an emergent
      system level property of the overall T cell receptor repertoire. We propose that
      tolerance is established at the level of the antigen presenting cell/T cell
      cluster, which facilitates and integrates cooperative interactions between T
      cells of different specificities. The threshold for self-reactivity is therefore
      imposed at a population level, and not at the level of the individual T
      cell/antigen encounter. Mathematically, the model can be formulated as a linear
      programing optimization problem that can be implemented as a multiplicative
      update algorithm, which shows a rapid convergence to a stable state. The model
      constrains self-reactivity within a predefined threshold, but maintains
      repertoire diversity and cross reactivity which are key characteristics of human
      T cell immunity. We show further that the size of individual clones in the model
      repertoire becomes heterogeneous, and that new clones can establish themselves
      even when the repertoire has stabilized. Our study combines the salient features
      of the "danger" model of self/non-self discrimination with the concepts of quorum
      sensing, and extends repertoire generation models to encompass the establishment
      of tolerance. Furthermore, the dynamic and continuous repertoire reshaping, which
      underlies tolerance in this model, suggests opportunities for therapeutic
      intervention to achieve long-term tolerance following transplantation. 

PMID- 26300882
TI  - Mast Cells as Regulators of T Cell Responses.
AB  - Mast cells (MCs) are recognized to participate in the regulation of innate and
      adaptive immune responses. Owing to their strategic location at the host
      environment interface, they control tissue homeostasis and are key cells for
      starting early host defense against intruders. Upon degranulation induced, e.g.,
      by immunoglobulin E (IgE) and allergen-mediated engagement of the high-affinity
      IgE receptor, complement or certain neuropeptide receptors, MCs release a wide
      variety of preformed and newly synthesized products including proteases, lipid
      mediators, and many cytokines, chemokines, and growth factors. Interestingly,
      increasing evidence suggests a regulatory role for MCs in inflammatory diseases
      via the regulation of T cell activities. Furthermore, rather than only serving as
      effector cells, MCs are now recognized to induce T cell activation, recruitment,
      proliferation, and cytokine secretion in an antigen-dependent manner and to
      impact on regulatory T cells. This review synthesizes recent developments in MC-T
      cell interactions, discusses their biological and clinical relevance, and
      explores recent controversies in this field of MC research. 

PMID- 26300883
TI  - Dietary Mannan Oligosaccharides: Counteracting the Side Effects of Soybean Meal
      Oil Inclusion on European Sea Bass (Dicentrarchus labrax) Gut Health and Skin
      Mucosa Mucus Production?
AB  - The main objective of this study was to assess the effects of 4 g kg(-1) dietary
      mannan oligosaccharides (MOS) inclusion in soybean oil (SBO)- and fish oil (FO)
      based diets on the gut health and skin mucosa mucus production of European sea
      bass juveniles after 8 weeks of feeding. Dietary MOS, regardless of the oil
      source, promoted growth. The intestinal somatic index was not affected, however
      dietary SBO reduced the intestinal fold length, while dietary MOS increased it.
      The dietary oil source fed produced changes on the posterior intestine fatty acid
      profiles irrespective of MOS dietary supplementation. SBO down-regulated the gene
      expression of TCRbeta, COX2, IL-1beta, TNFalpha, IL-8, IL-6, IL-10, TGFbeta, and
      Ig and up-regulated MHCII. MOS supplementation up-regulated the expression of
      MHCI, CD4, COX2, TNFalpha, and Ig when included in FO-based diets. However, there
      was a minor up-regulating effect on these genes when MOS was supplemented in the
      SBO-based diet. Both dietary oil sources and MOS affected mean mucous cell areas
      within the posterior gut, however the addition of MOS to a SBO diet increased the
      mucous cell size over the values shown in FO fed fish. Dietary SBO also trends to
      reduce mucous cell density in the anterior gut relative to FO, suggesting a lower
      overall mucosal secretion. There are no effects of dietary oil or MOS in the skin
      mucosal patterns. Complete replacement of FO by SBO, modified the gut fatty acid
      profile, altered posterior gut-associated immune system (GALT)-related gene
      expression and gut mucous cells patterns, induced shorter intestinal folds and
      tended to reduce European sea bass growth. However, when combined with MOS, the
      harmful effects of SBO appear to be partially balanced by moderating the down
      regulation of certain GALT-related genes involved in the functioning of gut
      mucous barrier and increasing posterior gut mucous cell diffusion rates, thus
      helping to preserve immune homeostasis. This denotes the importance of a balanced
      dietary n-3/n-6 ratio for an appropriate GALT-immune response against MOS in
      European sea bass juveniles. 

PMID- 26300881
TI  - The Dipeptidyl Peptidase Family, Prolyl Oligopeptidase, and Prolyl
      Carboxypeptidase in the Immune System and Inflammatory Disease, Including
      Atherosclerosis.
AB  - Research from over the past 20 years has implicated dipeptidyl peptidase (DPP) IV
      and its family members in many processes and different pathologies of the immune
      system. Most research has been focused on either DPPIV or just a few of its
      family members. It is, however, essential to consider the entire DPP family when
      discussing any one of its members. There is a substantial overlap between family
      members in their substrate specificity, inhibitors, and functions. In this
      review, we provide a comprehensive discussion on the role of prolyl-specific
      peptidases DPPIV, FAP, DPP8, DPP9, dipeptidyl peptidase II, prolyl
      carboxypeptidase, and prolyl oligopeptidase in the immune system and its
      diseases. We highlight possible therapeutic targets for the prevention and
      treatment of atherosclerosis, a condition that lies at the frontier between
      inflammation and cardiovascular disease. 

PMID- 26300884
TI  - The Contribution of Chemokines and Migration to the Induction of Central
      Tolerance in the Thymus.
AB  - As T cells develop, they migrate throughout the thymus where they undergo
      essential bi-directional signaling with stromal cells in distinct thymic
      microenvironments. Immature thymocyte progenitors are located in the thymic
      cortex. Following T cell receptor expression and positive selection, thymocytes
      undergo a dramatic transition: they become rapidly motile and relocate to the
      thymic medulla. Antigen-presenting cells (APCs) within the cortex and medulla
      display peptides derived from a wide array of self-proteins, which promote
      thymocyte self-tolerance. If a thymocyte is auto-reactive against such antigens,
      it undergoes either negative selection, via apoptosis, or differentiation into
      the regulatory T cell lineage. This induction of central tolerance is critical
      for prevention of autoimmunity. Chemokines and adhesion molecules play an
      essential role in tolerance induction, as they promote migration of developing
      thymocytes through the different thymic microenvironments and enhance
      interactions with APCs displaying self-antigens. Herein, we review the
      contribution of chemokines and other regulators of thymocyte localization and
      motility to T cell development, with a focus on their contribution to the
      induction of central tolerance. 

PMID- 26300885
TI  - Recognition of Microbial Glycolipids by Natural Killer T Cells.
AB  - T cells can recognize microbial antigens when presented by dedicated antigen
      presenting molecules. While peptides are presented by classical members of the
      major histocompatibility complex (MHC) family (MHC I and II), lipids,
      glycolipids, and lipopeptides can be presented by the non-classical MHC member,
      CD1. The best studied subset of lipid-reactive T cells are type I natural killer
      T (iNKT) cells that recognize a variety of different antigens when presented by
      the non-classical MHCI homolog CD1d. iNKT cells have been shown to be important
      for the protection against various microbial pathogens, including B. burgdorferi,
      the causative agents of Lyme disease, and S. pneumoniae, which causes
      pneumococcal meningitis and community-acquired pneumonia. Both pathogens carry
      microbial glycolipids that can trigger the T cell antigen receptor (TCR), leading
      to iNKT cell activation. iNKT cells have an evolutionary conserved TCR alpha
      chain, yet retain the ability to recognize structurally diverse glycolipids. They
      do so using a conserved recognition mode, in which the TCR enforces a conserved
      binding orientation on CD1d. TCR binding is accompanied by structural changes
      within the TCR binding site of CD1d, as well as the glycolipid antigen itself. In
      addition to direct recognition of microbial antigens, iNKT cells can also be
      activated by a combination of cytokines (IL-12/IL-18) and TCR stimulation. Many
      microbes carry TLR antigens, and microbial infections can lead to TLR activation.
      The subsequent cytokine response in turn lower the threshold of TCR-mediated iNKT
      cell activation, especially when weak microbial or even self-antigens are
      presented during the cause of the infection. In summary, iNKT cells can be
      directly activated through TCR triggering of strong antigens, while cytokines
      produced by the innate immune response may be necessary for TCR triggering and
      iNKT cell activation in the presence of weak antigens. Here, we will review the
      molecular basis of iNKT cell recognition of glycolipids, with an emphasis on
      microbial glycolipids. 

PMID- 26300887
TI  - The Importance of the CXCL12/CXCR4 Axis in Therapeutic Approaches to Diabetes
      Mellitus Attenuation.
AB  - The pleiotropic chemokine (C-X-C motif) ligand 12 (CXCL12) has emerged as a
      crucial player in several diseases. The role of CXCL12 in diabetes promotion and
      progression remains elusive due to its multiple functions and the overwhelming
      complexity of diabetes. Diabetes is a metabolic disorder resulting from a failure
      in glucose regulation due to beta-cell loss and/or dysfunction. In view of its
      ability to stimulate the regeneration, proliferation, and survival of beta-cells,
      as well as its capacity to sustain local immune-isolation, CXCL12 has been
      considered in approaches aimed at attenuating type 1 diabetes. However, a note of
      caution emerges from examinations of the involvement of CXCL12 in the development
      of diabetes and its complications, as research data indicate that CXCL12 displays
      effects that range from protective to detrimental. Therefore, as a beneficial
      effect of CXCL12 in one process could have deleterious consequences in another, a
      more complete understanding of CXCL12 effects, in particular its functioning in
      the cellular microenvironment, is essential before CXCL12 can be considered in
      therapies for diabetes treatment. 

PMID- 26300888
TI  - TRPM2 Channel-Mediated ROS-Sensitive Ca(2+) Signaling Mechanisms in Immune Cells.
AB  - Transient receptor potential melastatin 2 (TRPM2) proteins form Ca(2+)-permeable
      cationic channels that are potently activated by reactive oxygen species (ROS).
      ROS are produced during immune responses as signaling molecules as well as anti
      microbial agents. ROS-sensitive TRPM2 channels are widely expressed in cells of
      the immune system and located on the cell surface as a Ca(2+) influx pathway in
      macrophages, monocytes, neutrophils, lymphocytes, and microglia but
      preferentially within the lysosomal membranes as a Ca(2+) release mechanism in
      dendritic cells; ROS activation of the TRPM2 channels, regardless of the
      subcellular location, results in an increase in the intracellular Ca(2+)
      concentrations. Recent studies have revealed that TRPM2-mediated ROS-sensitive
      Ca(2+) signaling mechanisms play a crucial role in a number of processes and
      functions in immune cells. This mini-review discusses the recent advances in
      revelation of the various roles the TRPM2 channels have in immune cell functions
      and the implications in inflammatory diseases. 

PMID- 26300889
TI  - Comparative analysis of root transcriptomes from two contrasting drought
      responsive Williams 82 and DT2008 soybean cultivars under normal and dehydration
      conditions.
AB  - The economically important DT2008 and the model Williams 82 (W82) soybean
      cultivars were reported to have differential drought-tolerant degree to
      dehydration and drought, which was associated with root trait. Here, we used 66K
      Affymetrix Soybean Array GeneChip to compare the root transcriptomes of DT2008
      and W82 seedlings under normal, as well as mild (2 h treatment) and severe (10 h
      treatment) dehydration conditions. Out of the 38172 soybean genes annotated with
      high confidence, 822 (2.15%) and 632 (1.66%) genes showed altered expression by
      dehydration in W82 and DT2008 roots, respectively, suggesting that a larger
      machinery is required to be activated in the drought-sensitive W82 cultivar to
      cope with the stress. We also observed that long-term dehydration period induced
      expression change of more genes in soybean roots than the short-term one,
      independently of the genotypes. Furthermore, our data suggest that the higher
      drought tolerability of DT2008 might be attributed to the higher number of genes
      induced in DT2008 roots than in W82 roots by early dehydration, and to the
      expression changes of more genes triggered by short-term dehydration than those
      by prolonged dehydration in DT2008 roots vs. W82 roots. Differentially expressed
      genes (DEGs) that could be predicted to have a known function were further
      analyzed to gain a basic understanding on how soybean plants respond to
      dehydration for their survival. The higher drought tolerability of DT2008 vs. W82
      might be attributed to differential expression in genes encoding osmoprotectant
      biosynthesis-, detoxification- or cell wall-related proteins, kinases,
      transcription factors and phosphatase 2C proteins. This research allowed us to
      identify genetic components that contribute to the improved drought tolerance of
      DT2008, as well as provide a useful genetic resource for in-depth functional
      analyses that ultimately leads to development of soybean cultivars with improved
      tolerance to drought. 

PMID- 26300890
TI  - Resource-use efficiency explains grassy weed invasion in a low-resource savanna
      in north Australia.
AB  - Comparative studies of plant resource use and ecophysiological traits of invasive
      and native resident plant species can elucidate mechanisms of invasion success
      and ecosystem impacts. In the seasonal tropics of north Australia, the alien C4
      perennial grass Andropogon gayanus (gamba grass) has transformed diverse, mixed
      tree-grass savanna ecosystems into dense monocultures. To better understand the
      mechanisms of invasion, we compared resource acquisition and usage efficiency
      using leaf-scale ecophysiological and stand-scale growth traits of A. gayanus
      with a co-habiting native C4 perennial grass Alloteropsis semialata. Under wet
      season conditions, A. gayanus had higher rates of stomatal conductance,
      assimilation, and water use, plus a longer daily assimilation period than the
      native species A. semialata. Growing season length was also ~2 months longer for
      the invader. Wet season measures of leaf scale water use efficiency (WUE) and
      light use efficiency (LUE) did not differ between the two species, although
      photosynthetic nitrogen use efficiency (PNUE) was significantly higher in A.
      gayanus. By May (dry season) the drought avoiding native species A. semialata had
      senesced. In contrast, rates of A. gayanus gas exchange was maintained into the
      dry season, albeit at lower rates that the wet season, but at higher WUE and
      PNUE, evidence of significant physiological plasticity. High PNUE and leaf (15)N
      isotope values suggested that A. gayanus was also capable of preferential uptake
      of soil ammonium, with utilization occurring into the dry season. High PNUE and
      fire tolerance in an N-limited and highly flammable ecosystem confers a
      significant competitive advantage over native grass species and a broader niche
      width. As a result A. gayanus is rapidly spreading across north Australia with
      significant consequences for biodiversity and carbon and retention. 

PMID- 26300886
TI  - Prognostic and Predictive Value of DAMPs and DAMP-Associated Processes in Cancer.
AB  - It is now clear that human neoplasms form, progress, and respond to therapy in
      the context of an intimate crosstalk with the host immune system. In particular,
      accumulating evidence demonstrates that the efficacy of most, if not all, chemo-
      and radiotherapeutic agents commonly employed in the clinic critically depends on
      the (re)activation of tumor-targeting immune responses. One of the mechanisms
      whereby conventional chemotherapeutics, targeted anticancer agents, and
      radiotherapy can provoke a therapeutically relevant, adaptive immune response
      against malignant cells is commonly known as "immunogenic cell death."
      Importantly, dying cancer cells are perceived as immunogenic only when they emit
      a set of immunostimulatory signals upon the activation of intracellular stress
      response pathways. The emission of these signals, which are generally referred to
      as "damage-associated molecular patterns" (DAMPs), may therefore predict whether
      patients will respond to chemotherapy or not, at least in some settings. Here, we
      review clinical data indicating that DAMPs and DAMP-associated stress responses
      might have prognostic or predictive value for cancer patients. 

PMID- 26300891
TI  - Optimal level of purple acid phosphatase5 is required for maintaining complete
      resistance to Pseudomonas syringae.
AB  - Plants possess an exceedingly complex innate immune system to defend against most
      pathogens. However, a relative proportion of the pathogens overcome host's innate
      immunity and impair plant growth and productivity. We previously showed that
      mutation in purple acid phosphatase (PAP5) lead to enhanced susceptibility of
      Arabidopsis to the bacterial pathogen Pseudomonas syringae pv. tomato DC3000 (Pst
      DC3000). Here, we report that an optimal level of PAP5 is crucial for mounting
      complete basal resistance. Overexpression of PAP5 impaired ICS1, PR1 expression
      and salicylic acid (SA) accumulation similar to pap5 knockout mutant plants.
      Moreover, plant overexpressing PAP5 was impaired in H2O2 accumulation in response
      to Pst DC3000. PAP5 is localized in to peroxisomes, a known site of generation of
      reactive oxygen species for activation of defense responses. Taken together, our
      results demonstrate that optimal levels of PAP5 is required for mounting
      resistance against Pst DC3000 as both knockout and overexpression of PAP5 lead to
      compromised basal resistance. 

PMID- 26300893
TI  - Functional characterization and expression analysis of rice delta(1)-pyrroline-5
      carboxylate dehydrogenase provide new insight into the regulation of proline and
      arginine catabolism.
AB  - While intracellular proline accumulation in response to various stress conditions
      has been investigated in great detail, the biochemistry and physiological
      relevance of proline degradation in plants is much less understood. Moreover, the
      second and last step in proline catabolism, the oxidation of delta(1)-pyrroline-5
      carboxylic acid (P5C) to glutamate, is shared with arginine catabolism. Little
      information is available to date concerning the regulatory mechanisms
      coordinating these two pathways. Expression of the gene coding for P5C
      dehydrogenase was analyzed in rice by real-time PCR either following the
      exogenous supply of amino acids of the glutamate family, or under hyperosmotic
      stress conditions. The rice enzyme was heterologously expressed in E. coli, and
      the affinity-purified protein was thoroughly characterized with respect to
      structural and functional properties. A tetrameric oligomerization state was
      observed in size exclusion chromatography, which suggests a structure of the
      plant enzyme different from that shown for the bacterial P5C dehydrogenases
      structurally characterized to date. Kinetic analysis accounted for a preferential
      use of NAD(+) as the electron acceptor. Cations were found to modulate enzyme
      activity, whereas anion effects were negligible. Several metal ions were
      inhibitory in the micromolar range. Interestingly, arginine also inhibited the
      enzyme at higher concentrations, with a mechanism of uncompetitive type with
      respect to P5C. This implies that millimolar levels of arginine would increase
      the affinity of P5C dehydrogenase toward its specific substrate. Results are
      discussed in view of the involvement of the enzyme in either proline or arginine
      catabolism. 

PMID- 26300892
TI  - Secondary metabolites in fungus-plant interactions.
AB  - Fungi and plants are rich sources of thousands of secondary metabolites. The
      genetically coded possibilities for secondary metabolite production, the stimuli
      of the production, and the special phytotoxins basically determine the
      microscopic fungi-host plant interactions and the pathogenic lifestyle of fungi.
      The review introduces plant secondary metabolites usually with antifungal effect
      as well as the importance of signaling molecules in induced systemic resistance
      and systemic acquired resistance processes. The review also concerns the
      mimicking of plant effector molecules like auxins, gibberellins and abscisic acid
      by fungal secondary metabolites that modulate plant growth or even can subvert
      the plant defense responses such as programmed cell death to gain nutrients for
      fungal growth and colonization. It also looks through the special secondary
      metabolite production and host selective toxins of some significant fungal
      pathogens and the plant response in form of phytoalexin production. New results
      coming from genome and transcriptional analyses in context of selected fungal
      pathogens and their hosts are also discussed. 

PMID- 26300894
TI  - Suppressor mutations in the Glutamine Dumper1 protein dissociate disturbance in
      amino acid transport from other characteristics of the Gdu1D phenotype.
AB  - Intracellular amino acid transport across plant membranes is critical for
      metabolic pathways which are often split between different organelles. In
      addition, transport of amino acids across the plasma membrane enables the
      distribution of organic nitrogen through the saps between leaves and developing
      organs. Amino acid importers have been studied for more than two decades, and
      their role in this process is well-documented. While equally important, amino
      acid exporters are not well-characterized. The over-expression of GDU1, encoding
      a small membrane protein with one transmembrane domain, leads to enhancement of
      amino acid export by Arabidopsis cells, glutamine secretion at the leaf margin,
      early senescence and size reduction of the plant, possibly caused by the
      stimulation of amino acid exporter(s). Previous work reported the identification
      of suppressor mutations of the GDU1 over-expression phenotype, which affected the
      GDU1 and LOG2 genes, the latter encoding a membrane-bound ubiquitin ligase
      interacting with GDU1. The present study focuses on the characterization of three
      additional suppressor mutations affecting GDU1. Size, phenotype, glutamine
      transport and amino acid tolerance were recorded for recapitulation plants and
      over-expressors of mutagenized GDU1 proteins. Unexpectedly, the over-expression
      of most mutated GDU1 led to plants with enhanced amino acid export, but failing
      to display secretion of glutamine and size reduction. The results show that the
      various effects triggered by GDU1 over-expression can be dissociated from one
      another by mutagenizing specific residues. The fact that these residues are not
      necessarily conserved suggests that the diverse biochemical properties of the
      GDU1 protein are not only born by the characterized transmembrane and VIMAG
      domains. These data provide a better understanding of the structure/function
      relationships of GDU1 and may enable modifying amino acid export in plants
      without detrimental effects on plant fitness. 

PMID- 26300895
TI  - New insights into plant glycoside hydrolase family 32 in Agave species.
AB  - In order to optimize the use of agaves for commercial applications, an
      understanding of fructan metabolism in these species at the molecular and genetic
      level is essential. Based on transcriptome data, this report describes the
      identification and molecular characterization of cDNAs and deduced amino acid
      sequences for genes encoding fructosyltransferases, invertases and fructan
      exohydrolases (FEH) (enzymes belonging to plant glycoside hydrolase family 32)
      from four different agave species (A. tequilana, A. deserti, A. victoriae
      reginae, and A. striata). Conserved amino acid sequences and a hypervariable
      domain allowed classification of distinct isoforms for each enzyme type. Notably
      however neither 1-FFT nor 6-SFT encoding cDNAs were identified. In silico
      analysis revealed that distinct isoforms for certain enzymes found in a single
      species, showed different levels and tissue specific patterns of expression
      whereas in other cases expression patterns were conserved both within the species
      and between different species. Relatively high levels of in silico expression for
      specific isoforms of both invertases and fructosyltransferases were observed in
      floral tissues in comparison to vegetative tissues such as leaves and stems and
      this pattern was confirmed by Quantitative Real Time PCR using RNA obtained from
      floral and leaf tissue of A. tequilana. Thin layer chromatography confirmed the
      presence of fructans with degree of polymerization (DP) greater than DP three in
      both immature buds and fully opened flowers also obtained from A. tequilana. 

PMID- 26300896
TI  - Identification of cold-inducible microRNAs in grapevine.
AB  - Low temperature is one of the most important environmental factors that limits
      the geographical distribution and productivity of grapevine. However, the
      molecular mechanisms on how grapevine responds to cold stress remains to be
      elucidated. MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs
      that play an essential role during plant development and stress responses.
      Although miRNAs and their targets have been identified in several Vitis species,
      their participation during cold accumulation in grapevine remains unknown. In
      this study, two small RNA libraries were generated from micropropagated 'Muscat
      Hamburg' (V. vinifera) plantlets under normal and low temperatures (4 degrees C).
      A total of 163 known miRNAs and 67 putative novel miRNAs were detected from two
      small RNA libraries by Solexa sequencing. Forty-four cold-inducible miRNAs were
      identified through differentially expressed miRNAs (DEMs) analysis; among which,
      13 belonged to upregulated DEMs while 31 belonged downregulated DEMs. The
      expression patterns of the 13 DEMs were verified by real-time RT-PCR analysis.
      The prediction of the target genes for DEMs indicated that miRNA may regulate
      transcription factors, including AP2, SBP, MYB, bHLH, GRAS, and bZIP under cold
      stress. The 5'-RLM RACE were conducted to verify the cleavage site of predicted
      targets. Seven predicted target genes for four known and three novel vvi-miRNAs
      showed specific cleavage sites corresponding to their miRNA complementary
      sequences. The expression pattern of these seven target genes revealed negative
      correlation with the expression level of the corresponding vvi-miRNAs. Our
      results indicated that a diverse set of miRNAs in V. vinifera are cold-inducible
      and may play an important role in cold stress response. 

PMID- 26300897
TI  - Augmenting iron accumulation in cassava by the beneficial soil bacterium Bacillus
      subtilis (GBO3).
AB  - Cassava (Manihot esculenta), a major staple food in the developing world,
      provides a basic carbohydrate diet for over half a billion people living in the
      tropics. Despite the iron abundance in most soils, cassava provides insufficient
      iron for humans as the edible roots contain 3-12 times less iron than other
      traditional food crops such as wheat, maize, and rice. With the recent
      identification that the beneficial soil bacterium Bacillus subtilis (strain GB03)
      activates iron acquisition machinery to increase metal ion assimilation in
      Arabidopsis, the question arises as to whether this plant-growth promoting
      rhizobacterium also augments iron assimilation to increase endogenous iron levels
      in cassava. Biochemical analyses reveal that shoot-propagated cassava with GB03
      inoculation exhibit elevated iron accumulation after 140 days of plant growth as
      determined by X-ray microanalysis and total foliar iron analysis. Growth
      promotion and increased photosynthetic efficiency were also observed for
      greenhouse-grown plants with GB03-exposure. These results demonstrate the
      potential of microbes to increase iron accumulation in an important agricultural
      crop and is consistent with idea that microbial signaling can regulate plant
      photosynthesis. 

PMID- 26300898
TI  - Metabolite profiling of somatic embryos of Cyclamen persicum in comparison to
      zygotic embryos, endosperm, and testa.
AB  - Somatic embryogenesis has been shown to be an efficient in vitro plant
      regeneration system for many crops such as the important ornamental plant
      Cyclamen persicum, for which this regeneration pathway of somatic embryogenesis
      is of interest for the vegetative propagation of parental lines as well as elite
      plants. However, somatic embryogenesis is not commercially used in many crops due
      to several unsolved problems, such as malformations, asynchronous development,
      deficiencies in maturation and germination of somatic embryos. In contrast,
      zygotic embryos in seeds develop and germinate without abnormalities in most
      cases. Instead of time-consuming and labor-intensive experiments involving tests
      of different in vitro culture conditions and plant growth regulator supplements,
      we follow a more directed approach. Zygotic embryos served as a reference and
      were compared to somatic embryos in metabolomic analyses allowing the future
      optimization of the in vitro system. The aims of this study were to detect
      differences in the metabolite profiles of torpedo stage somatic and zygotic
      embryos of C. persicum. Moreover, major metabolites in endosperm and testa were
      identified and quantified. Two sets of extracts of two to four biological
      replicates each were analyzed. In total 52 metabolites were identified and
      quantified in the different tissues. One of the most significant differences
      between somatic and zygotic embryos was that the proline concentration in the
      zygotic embryos was about 40 times higher than that found in somatic embryos.
      Epicatechin, a scavenger for reactive oxygen species, was found in highest
      abundance in the testa. Sucrose, the most abundant metabolite was detected in
      significantly higher concentrations in zygotic embryos. Also, a yet unknown
      trisaccharide, was significantly enriched in zygotic embryos. 

PMID- 26300899
TI  - The novel and taxonomically restricted Ah24 gene from grain amaranth (Amaranthus
      hypochondriacus) has a dual role in development and defense.
AB  - Grain amaranths tolerate stress and produce highly nutritious seeds. We have
      identified several (a)biotic stress-responsive genes of unknown function in
      Amaranthus hypochondriacus, including the so-called Ah24 gene. Ah24 was expressed
      in young or developing tissues; it was also strongly induced by mechanical
      damage, insect herbivory and methyl jasmonate and in meristems and newly emerging
      leaves of severely defoliated plants. Interestingly, an in silico analysis of its
      1304 bp promoter region showed a predominance of regulatory boxes involved in
      development, but not in defense. The Ah24 cDNA encodes a predicted cytosolic
      protein of 164 amino acids, the localization of which was confirmed by confocal
      microscopy. Additional in silico analysis identified several other Ah24 homologs,
      present almost exclusively in plants belonging to the Caryophyllales. The
      possible function of this gene in planta was examined in transgenic Ah24
      overexpressing Arabidopsis thaliana and Nicotiana tabacum plants. Transformed
      Arabidopsis showed enhanced vegetative growth and increased leaf number with no
      penalty in one fitness component, such as seed yield, in experimental conditions.
      Transgenic tobacco plants, which grew and reproduced normally, had increased
      insect herbivory resistance. Modified vegetative growth in transgenic Arabidopsis
      coincided with significant changes in the expression of genes controlling
      phytohormone synthesis or signaling, whereas increased resistance to insect
      herbivory in transgenic tobacco coincided with higher jasmonic acid and
      proteinase inhibitor activity levels, plus the accumulation of nicotine and
      several other putative defense-related metabolites. It is proposed that the
      primary role of the Ah24 gene in A. hypochondriacus is to contribute to a rapid
      recovery post-wounding or defoliation, although its participation in defense
      against insect herbivory is also plausible. 

PMID- 26300900
TI  - Proteomic and metabolic traits of grape exocarp to explain different anthocyanin
      concentrations of the cultivars.
AB  - The role of grape berry skin as a protective barrier against damage by physical
      injuries and pathogen attacks requires a metabolism able to sustain biosynthetic
      activities such as those relating to secondary compounds (i.e., flavonoids). In
      order to draw the attention on these biochemical processes, a proteomic and
      metabolomic comparative analysis was performed among Riesling Italico, Pinot
      Gris, Pinot Noir, and Croatina cultivars, which are known to accumulate
      anthocyanins to a different extent. The application of multivariate statistics on
      the dataset pointed out that the cultivars were distinguishable from each other
      and the order in which they were grouped mainly reflected their relative
      anthocyanin contents. Sorting the spots according to their significance 100
      proteins were characterized by LC-ESI-MS/MS. Through GC-MS, performed in Selected
      Ion Monitoring (SIM) mode, 57 primary metabolites were analyzed and the
      differences in abundance of 16 of them resulted statistically significant to
      ANOVA test. Considering the functional distribution, the identified proteins were
      involved in many physiological processes such as stress, defense, carbon
      metabolism, energy conversion and secondary metabolism. The trends of some
      metabolites were related to those of the protein data. Taken together, the
      results permitted to highlight the relationships between the secondary compound
      pathways and the main metabolism (e.g., glycolysis and TCA cycle). Moreover, the
      trend of accumulation of many proteins involved in stress responses, reinforced
      the idea that they could play a role in the cultivar specific developmental plan.

PMID- 26300901
TI  - High-throughput sequencing reveals miRNA effects on the primary and secondary
      production properties in long-term subcultured Taxus cells.
AB  - Plant-cell culture technology is a promising alternative for production of high
      value secondary metabolites but is limited by the decreased metabolite production
      after long-term subculture. The goal of this study was to determine the effects
      of miRNAs on altered gene expression profiles during long-term subculture. Two
      Taxus cell lines, CA (subcultured for 10 years) and NA (subcultured for 6
      months), were high-throughput sequenced at the mRNA and miRNA levels. A total of
      265 known (78.87% of 336) and 221 novel (79.78% of 277) miRNAs were
      differentially expressed. Furthermore, 67.17% of the known differentially
      expressed (DE) miRNAs (178) and 60.63% of the novel DE-miRNAs (134) were
      upregulated in NA. A total of 275 inverse-related miRNA/mRNA modules were
      identified by target prediction analysis. Functional annotation of the targets
      revealed that the high-ranking miRNA targets were those implicated in primary
      metabolism and abiotic or biotic signal transduction. For example, various genes
      for starch metabolism and oxidative phosphorylation were inversely related to the
      miRNA levels, thereby indicating that miRNAs have important roles in these
      pathways. Interestingly, only a few genes for secondary metabolism were inversely
      related to miRNA, thereby indicating that factors other than miRNA are present in
      the regulatory system. Moreover, miR8154 and miR5298b were upregulated miRNAs
      that targeted a mass of DE genes. The overexpression of these miRNAs in CA
      increased the genes of taxol, phenylpropanoid, and flavonoid biosynthesis,
      thereby suggesting their function as crucial factors that regulate the entire
      metabolic network during long-term subculture. Our current studies indicated that
      a positive conversion of production properties from secondary metabolism to
      primary metabolism occurred in long-term subcultured cells. miRNAs are important
      regulators in the upregulation of primary metabolism. 

PMID- 26300902
TI  - Using the pathogen-host interactions database (PHI-base) to investigate plant
      pathogen genomes and genes implicated in virulence.
AB  - New pathogen-host interaction mechanisms can be revealed by integrating mutant
      phenotype data with genetic information. PHI-base is a multi-species manually
      curated database combining peer-reviewed published phenotype data from plant and
      animal pathogens and gene/protein information in a single database. 

PMID- 26300903
TI  - A comparative method for protein extraction and 2-D gel electrophoresis from
      different tissues of Cajanus cajan.
AB  - Pigeonpea is an important legume crop with high protein content. However, it is
      often subjected to various abiotic and biotic stresses. Proteomics is a state-of
      the-art technique used to analyze the protein profiling of a tissue for
      deciphering the molecular entities that could be manipulated for developing crops
      resistant to these stresses. In this context, developing a comprehensive proteome
      profile from different vegetative and reproductive tissues has become mandatory.
      Although several protein extraction protocols from different tissues of diverse
      plant species have been reported, there is no report for pigeonpea. Here, we
      report tissue-specific protein extraction protocols representing vegetative
      (young leaves), and reproductive (flowers and seeds) organs and their subsequent
      analysis on 2-dimensional gel electrophoresis. The study explicitly demonstrated
      that the efficacy of a particular protein extraction protocol is dependent on the
      different tissues, such as leaves, flowers and seeds that differ in their
      structure and metabolic constituents. For instance, phenol-based protocol showed
      an efficacy toward higher protein yield, better spot resolution and a minimal
      streaking on 2-DE gel for both leaves and flowers. Protein extraction from seeds
      was best achieved by employing phosphate-TCA-acetone protocol. 

PMID- 26300905
TI  - Plant genotype, microbial recruitment and nutritional security.
AB  - Agricultural food products with high nutritional value should always be preferred
      over food products with low nutritional value. Efforts are being made to increase
      nutritional value of food by incorporating dietary supplements to the food
      products. The same is more desirous if the nutritional value of food is increased
      under natural environmental conditions especially in agricultural farms.
      Fragmented researches have demonstrated possibilities in achieving the same. The
      rhizosphere is vital in this regard for not only health and nutritional status of
      plants but also for the microorganisms colonizing the rhizosphere. Remarkably
      robust composition of plant microbiome with respect to other soil environments
      clearly suggests the role of a plant host in discriminating its colonizers
      (Zancarini et al., 2012). A large number of biotic and abiotic factors are
      believed to manipulate the microbial communities in the rhizosphere. However,
      plant genotype has proven to be the key in giving the final shape of the
      rhizosphere microbiome (Berendsen et al., 2012; Marques et al., 2014). 

PMID- 26300904
TI  - Genome-wide identification of sweet orange (Citrus sinensis) histone modification
      gene families and their expression analysis during the fruit development and
      fruit-blue mold infection process.
AB  - In eukaryotes, histone acetylation and methylation have been known to be involved
      in regulating diverse developmental processes and plant defense. These histone
      modification events are controlled by a series of histone modification gene
      families. To date, there is no study regarding genome-wide characterization of
      histone modification related genes in citrus species. Based on the two recent
      sequenced sweet orange genome databases, a total of 136 CsHMs (Citrus sinensis
      histone modification genes), including 47 CsHMTs (histone methyltransferase
      genes), 23 CsHDMs (histone demethylase genes), 50 CsHATs (histone
      acetyltransferase genes), and 16 CsHDACs (histone deacetylase genes) were
      identified. These genes were categorized to 11 gene families. A comprehensive
      analysis of these 11 gene families was performed with chromosome locations,
      phylogenetic comparison, gene structures, and conserved domain compositions of
      proteins. In order to gain an insight into the potential roles of these genes in
      citrus fruit development, 42 CsHMs with high mRNA abundance in fruit tissues were
      selected to further analyze their expression profiles at six stages of fruit
      development. Interestingly, a numbers of genes were expressed highly in flesh of
      ripening fruit and some of them showed the increasing expression levels along
      with the fruit development. Furthermore, we analyzed the expression patterns of
      all 136 CsHMs response to the infection of blue mold (Penicillium digitatum),
      which is the most devastating pathogen in citrus post-harvest process. The
      results indicated that 20 of them showed the strong alterations of their
      expression levels during the fruit-pathogen infection. In conclusion, this study
      presents a comprehensive analysis of the histone modification gene families in
      sweet orange and further elucidates their behaviors during the fruit development
      and the blue mold infection responses. 

PMID- 26300906
TI  - High intraspecific ability to adjust both carbon uptake and allocation under
      light and nutrient reduction in Halimium halimifolium L.
AB  - The allocation of recently assimilated carbon (C) by plants depends on
      developmental stage and on environmental factors, but the underlying mechanisms
      are still a matter of debate. In the present study, we investigated the
      regulation of C uptake and allocation and their adjustments during plant growth.
      We induced different allocation strategies in the Mediterranean shrub Halimium
      halimifolium L. by a reduction of light (Low L treatment) and nutrient
      availability (Low N treatment) and analyzed allocation parameters as well as
      morphological and physiological traits for 15 months. Further, we conducted a
      (13)CO2 pulse-labeling and followed the way of recently assimilated carbon to
      eight different tissue classes and respiration for 13 days. The plant responses
      were remarkably distinct in our study, with mainly morphological/physiological
      adaptions in case of light reduction and adjustment of C allocation in case of
      nutrient reduction. The transport of recently assimilated C to the root system
      was enhanced in amount (c. 200%) and velocity under nutrient limited conditions
      compared to control plants. Despite the 57% light reduction the total biomass
      production was not affected in the Low L treatment. The plants probably
      compensated light reduction by an improvement of their ability to fix C. Thus,
      our results support the concept that photosynthesis is, at least in a medium term
      perspective, influenced by the C demand of the plant and not exclusively by
      environmental factors. Finally, our results indicate that growing heterotrophic
      tissues strongly reduce the C reflux from storage and structural C pools and
      therefore enhance the fraction of recent assimilates allocated to respiration. We
      propose that this interruption of the C reflux from storage and structural C
      pools could be a regulation mechanism for C translocation in plants. 

PMID- 26300907
TI  - Functional characterization and reconstitution of ABA signaling components using
      transient gene expression in rice protoplasts.
AB  - The core components of ABA-dependent gene expression signaling have been
      identified in Arabidopsis and rice. This signaling pathway consists of four major
      components; group A OsbZIPs, SAPKs, subclass A OsPP2Cs and OsPYL/RCARs in rice.
      These might be able to make thousands of combinations through interaction
      networks resulting in diverse signaling responses. We tried to characterize those
      gene functions using transient gene expression for rice protoplasts (TGERP)
      because it is instantaneous and convenient system. Firstly, in order to monitor
      the ABA signaling output, we developed reporter system named pRab16A-fLUC which
      consists of Rab16A promoter of rice and luciferase gene. It responses more
      rapidly and sensitively to ABA than pABRC3-fLUC that consists of ABRC3 of HVA1
      promoter in TGERP. We screened the reporter responses for over-expression of each
      signaling components from group A OsbZIPs to OsPYL/RCARs with or without ABA in
      TGERP. OsbZIP46 induced reporter most strongly among OsbZIPs tested in the
      presence of ABA. SAPKs could activate the OsbZIP46 even in the ABA independence.
      Subclass A OsPP2C6 and -8 almost completely inhibited the OsbZIP46 activity in
      the different degree through the SAPK9. Lastly, OsPYL/RCAR2 and -5 rescued the
      OsbZIP46 activity in the presence of SAPK9 and OsPP2C6 dependent on ABA
      concentration and expression level. By using TGERP, we could characterize
      successfully the effects of ABA dependent gene expression signaling components in
      rice. In conclusion, TGERP represents very useful technology to study systemic
      functional genomics in rice or other monocots. 

PMID- 26300909
TI  - Broadening the definition of a bioinformatician.

PMID- 26300910
TI  - A new method for estimating the demographic history from DNA sequences: an
      importance sampling approach.
AB  - The effective population size over time (demographic history) can be retraced
      from a sample of contemporary DNA sequences. In this paper, we propose a novel
      methodology based on importance sampling (IS) for exploring such demographic
      histories. Our starting point is the generalized skyline plot with the main
      difference being that our procedure, skywis plot, uses a large number of
      genealogies. The information provided by these genealogies is combined according
      to the IS weights. Thus, we compute a weighted average of the effective
      population sizes on specific time intervals (epochs), where the genealogies that
      agree more with the data are given more weight. We illustrate by a simulation
      study that the skywis plot correctly reconstructs the recent demographic history
      under the scenarios most commonly considered in the literature. In particular,
      our method can capture a change point in the effective population size, and its
      overall performance is comparable with the one of the bayesian skyline plot. We
      also introduce the case of serially sampled sequences and illustrate that it is
      possible to improve the performance of the skywis plot in the case of an
      exponential expansion of the effective population size. 

PMID- 26300908
TI  - New insights from monogenic diabetes for "common" type 2 diabetes.
AB  - Boundaries between monogenic and complex genetic diseases are becoming
      increasingly blurred, as a result of better understanding of phenotypes and their
      genetic determinants. This had a large impact on the way complex disease genetics
      is now being investigated. Starting with conventional approaches like familial
      linkage, positional cloning and candidate genes strategies, the scope of complex
      disease genetics has grown exponentially with scientific and technological
      advances in recent times. Despite identification of multiple loci harboring
      common and rare variants associated with complex diseases, interpreting and
      evaluating their functional role has proven to be difficult. Information from
      monogenic diseases, especially related to the intermediate traits associated with
      complex diseases comes handy. The significant overlap between traits and
      phenotypes of monogenic diseases with related complex diseases provides a
      platform to understand the disease biology better. In this review, we would
      discuss about one such complex disease, type 2 diabetes, which shares marked
      similarity of intermediate traits with different forms of monogenic diabetes. 

PMID- 26300911
TI  - Correcting for the study bias associated with protein-protein interaction
      measurements reveals differences between protein degree distributions from
      different cancer types.
AB  - Protein-protein interaction (PPI) networks are associated with multiple types of
      biases partly rooted in technical limitations of the experimental techniques.
      Another source of bias are the different frequencies with which proteins have
      been studied for interaction partners. It is generally believed that proteins
      with a large number of interaction partners tend to be essential, evolutionarily
      conserved, and involved in disease. It has been repeatedly reported that proteins
      driving tumor formation have a higher number of PPI partners. However, it has
      been noticed before that the degree distribution of PPI networks is biased toward
      disease proteins, which tend to have been studied more often than non-disease
      proteins. At the same time, for many poorly characterized proteins no
      interactions have been reported yet. It is unclear to which extent this study
      bias affects the observation that cancer proteins tend to have more PPI partners.
      Here, we show that the degree of a protein is a function of the number of times
      it has been screened for interaction partners. We present a randomization-based
      method that controls for this bias to decide whether a group of proteins is
      associated with significantly more PPI partners than the proteomic background. We
      apply our method to cancer proteins and observe, in contrast to previous studies,
      no conclusive evidence for a significantly higher degree distribution associated
      with cancer proteins as compared to non-cancer proteins when we compare them to
      proteins that have been equally often studied as bait proteins. Comparing
      proteins from different tumor types, a more complex picture emerges in which
      proteins of certain cancer classes have significantly more interaction partners
      while others are associated with a smaller degree. For example, proteins of
      several hematological cancers tend to be associated with a higher number of
      interaction partners as expected by chance. Solid tumors, in contrast, are
      usually associated with a degree distribution similar to those of equally often
      studied random protein sets. We discuss the biological implications of these
      findings. Our work shows that accounting for biases in the PPI network is
      possible and increases the value of PPI data. 

PMID- 26300912
TI  - Commentary: Portuguese crypto-Jews: the genetic heritage of a complex history.

PMID- 26300913
TI  - Can the second law of thermodynamics hold in cell cultures?

PMID- 26300914
TI  - Comparative Effect of Lisinopril and Fosinopril in Mitigating Learning and Memory
      Deficit in Scopolamine-Induced Amnesic Rats.
AB  - Lisinopril and fosinopril were compared on scopolamine-induced learning and
      memory deficits in rats. A total of eighty-four male Wistar rats were divided
      into seven groups. Group I received 2% gum acacia orally for 4 weeks, group II
      received normal saline, and group III received scopolamine (2 mg/kg/ip) as single
      dose. Groups IV and V received lisinopril ( 0.225 mg/kg and 0.45 mg/kg), while
      Groups VI and VII received fosinopril (0.90 mg/kg and 1.80 mg/kg), respectively,
      orally for four weeks, followed by scopolamine (2 mg/kg/ip) given 45 minutes
      prior to experimental procedure. Evaluation of learning and memory was assessed
      by using passive avoidance, Morris water maze, and elevated plus maze tests
      followed by analysis of hippocampal morphology and quantification of the number
      of surviving neurons. Scopolamine induced marked impairment of memory in
      behavioral tests which correlated with morphological changes in hippocampus.
      Pretreatment with fosinopril 1.80 mg/kg was found to significantly ameliorate the
      memory deficits and hippocampal degeneration induced by scopolamine. Fosinopril
      exhibits antiamnesic activity, indicating its possible role in preventing memory
      deficits seen in dementia though the precise mechanism underlying this effect
      needs to be further evaluated. 

PMID- 26300916
TI  - An International Survey of Health Care Providers Involved in the Management of
      Cancer Patients Exposed to Cardiotoxic Therapy.
AB  - Cardiotoxicity is the second leading cause of morbidity and mortality in cancer
      survivors. The objective of this international cardiac oncology survey was to
      gain a better understanding of current knowledge and practice patterns among HCPs
      involved in the management of cancer patients exposed to potentially cardiotoxic
      drugs. Between 2012 and 2013, we conducted an email-based survey of HCPs involved
      in the management of cardiac disease in cancer patients. 393 survey responses
      were received, of which 77 were from Canadian respondents. The majority of
      respondents were cardiologists (47%), followed closely by medical oncologists.
      The majority of respondents agreed that cardiac issues are important to cancer
      patients (97%). However, only 36% of total respondents agreed with an accepted
      definition of cardiotoxicity. While 78% of respondents felt that cardiac
      medications are protective during active cancer treatment, only 51% would
      consider prescribing these medications up-front in cancer patients. Although
      results confirm a high level of concern for cardiac safety, there continues to be
      a lack of consensus on the definition of cardiotoxicity and a discrepancy in
      clinical practice between cardiologists and oncologists. These differences in
      opinion require resolution through more effective research collaboration and
      formulation of evidence-based guidelines. 

PMID- 26300915
TI  - Multimodality Imaging in Cardiooncology.
AB  - Cardiotoxicity represents a rising problem influencing prognosis and quality of
      life of chemotherapy-treated patients. Anthracyclines and trastuzumab are the
      drugs most commonly associated with development of a cardiotoxic effect. Heart
      failure, myocardial ischemia, hypertension, myocarditis, and thrombosis are
      typical manifestation of cardiotoxicity by chemotherapeutic agents. Diagnosis and
      monitoring of cardiac side-effects of cancer treatment is of paramount
      importance. Echocardiography and nuclear medicine methods are widely used in
      clinical practice and left ventricular ejection fraction is the most important
      parameter to asses myocardial damage secondary to chemotherapy. However, left
      ventricular ejection decrease is a delayed phenomenon, occurring after a long
      stage of silent myocardial damage that classic imaging methods are not able to
      detect. New imaging techniques including three-dimensional echocardiography,
      speckle tracking echocardiography, and cardiac magnetic resonance have
      demonstrated high sensitivity in detecting the earliest alteration of left
      ventricular function associated with future development of chemotherapy-induced
      cardiomyopathy. Early diagnosis of cardiac involvement in cancer patients can
      allow for timely and adequate treatment management and the introduction of
      cardioprotective strategies. 

PMID- 26300917
TI  - Clinical Experience of Patients Referred to a Multidisciplinary Cardiac Oncology
      Clinic: An Observational Study.
AB  - Cardiotoxicity is the second leading cause of long-term morbidity and mortality
      among cancer survivors. The purpose of this retrospective observational study is
      to report on the clinical and cardiac outcomes in patients with early stage and
      advanced cancer who were referred to our multidisciplinary cardiac oncology
      clinic (COC). A total of 428 patients were referred to the COC between October
      2008 and January 2013. The median age of patients at time of cancer diagnosis was
      60. Almost half of patients who received cancer therapy received first-line
      chemotherapy alone (169, 41.7%), of which 84 (49.7%) were exposed to
      anthracyclines. The most common reasons for referral to the cardiac oncology
      clinic were decreased LVEF (34.6%), prechemotherapy assessment (11.9%), and
      arrhythmia (8.4%). A total of 175 (40.9%) patients referred to the COC were
      treated with cardiac medications. The majority (331, 77.3%) of patients were
      alive as of January 2013, and 93 (21.7%) patients were deceased. Through regular
      review of cardiac oncology clinic referral patterns, management plans, and
      patient outcomes, we aim to continuously improve delivery of cardiac care to our
      patient population and optimize cardiac health. 

PMID- 26300918
TI  - The Prevalence of Cardiac Risk Factors in Men with Localized Prostate Cancer
      Undergoing Androgen Deprivation Therapy in British Columbia, Canada.
AB  - Background. While androgen deprivation therapy (ADT) reduces the risk of prostate
      cancer-specific mortality in high-risk localized prostate cancer, it adversely
      affects cardiovascular (CV) risk factor profiles in treated men. Methods. We
      retrospectively reviewed the charts of 100 consecutive men with intermediate- or
      high-risk localized prostate cancer referred to the British Columbia Cancer
      Agency for ADT. Data on CV risk factors and disease were collected and Framingham
      risk scores were calculated. Results. The median age of the study cohort was 73
      years. Established cardiovascular disease was present in 25% of patients. Among
      patients without established CV disease, calculated Framingham risk was high in
      65%, intermediate in 33%, and low in 1%. Baseline hypertension was present in 58%
      of patients, dyslipidemia in 51%, and diabetes or impaired glucose tolerance in
      24%. Hypertension was more prevalent in the study cohort than in an age- and sex
      matched population sample (OR 1.74, P = 0.006); diabetes had a similar prevalence
      (OR 0.93, P = 0.8). Conclusions. Patients receiving ADT have a high prevalence of
      cardiovascular disease and risk factors and are more likely to be hypertensive
      than population controls. Low rates of CV risk screening suggest opportunities
      for improved primary and secondary prevention of CV disease in this population. 

PMID- 26300919
TI  - Amoxicillin/Clavulanic Acid for the Treatment of Odontogenic Infections: A
      Randomised Study Comparing Efficacy and Tolerability versus Clindamycin.
AB  - Background. Treatment of odontogenic infections includes surgical drainage and
      adjunctive antibiotics. This study was designed to generate efficacy and safety
      data to support twice daily dosing of amoxicillin/clavulanic acid compared to
      clindamycin in odontogenic infections. Methods. This was a phase IV, randomised,
      observer blind study; 472 subjects were randomised to receive
      amoxicillin/clavulanic acid (875 mg/125 mg BID, n = 235) or clindamycin (150 mg
      QID, n = 237) for 5 or 7 days based on clinical response. The primary endpoint
      was percentage of subjects achieving clinical success (composite measure of pain,
      swelling, fever, and additional antimicrobial therapy required) at the end of
      treatment. Results. The upper limit of two-sided 95% confidence interval for the
      treatment difference between the study arms (7.7%) was within protocol specified
      noninferiority margin of 10%, thus demonstrating noninferiority of
      amoxicillin/clavulanic acid to clindamycin. Secondary efficacy results showed a
      higher clinical success rate at Day 5 in the amoxicillin/clavulanic acid arm.
      Most adverse events (raised liver enzymes, diarrhoea, and headache) were similar
      across both arms and were of mild to moderate intensity. Conclusion.
      Amoxicillin/clavulanic acid was comparable to clindamycin in achieving clinical
      success (88.2% versus 89.7%) in acute odontogenic infections and the safety
      profile was consistent with the known side effects of both drugs. Trial
      Registration. This trial is registered with Clinicaltrials.gov identifier:
      NCT02141217. 

PMID- 26300920
TI  - Hematopoietic Stem and Immune Cells in Chronic HIV Infection.
AB  - Hematopoietic stem cell (HSC) belongs to multipotent adult somatic stem cells. A
      single HSC can reconstitute the entire blood system via self-renewal,
      differentiation into all lineages of blood cells, and replenishment of cells lost
      due to attrition or disease in a person's lifetime. Although all blood and immune
      cells derive from HSC, immune cells, specifically immune memory cells, have the
      properties of HSC on self-renewal and differentiation into lineage effector cells
      responding to the invading pathogens. Moreover, the interplay between immune
      memory cell and viral pathogen determines the course of a viral infection. Here,
      we state our point of view on the role of blood stem and progenitor cell in
      chronic HIV infection, with a focus on memory CD4 T-cell in the context of
      HIV/AIDS eradication and cure. 

PMID- 26300921
TI  - Analysis of the Pro- and Anti-Inflammatory Cytokines Secreted by Adult Stem Cells
      during Differentiation.
AB  - Adipose-derived stromal/stem cells (ASCs) are adult stem cells that have the
      potential to differentiate into mesenchymal lineage cells. The abundance of ASCs
      in adipose tissue and easy accessibility with relatively little donor site
      morbidity make them attractive candidate cells for tissue engineering and
      regenerative medicine. However, the underlying inflammatory process that occurs
      during ASC differentiation into adipocytes and osteoblast has not been
      extensively investigated. ASCs cultured in osteogenic and adipogenic
      differentiation medium were characterized by oil red o staining and alizarin red
      staining, respectively. ASCs undergoing osteogenic and adipogenic differentiation
      were isolated on days 7, 14, and 21 and assessed by qRT-PCR for the expression of
      pro- and anti-inflammatory cytokines. ASCs undergoing osteogenic differentiation
      expressed a distinct panel of cytokines that differed from the cytokine profile
      of ASCs undergoing adipogenic differentiation at each of the time points
      analyzed. Mapping the cytokine expression profile during ASC differentiation will
      provide insight into the role of inflammation in this process and identify
      potential targets that may aid in enhancing osteogenic or adipogenic
      differentiation for the purposes of tissue engineering and regenerative medicine.

PMID- 26300922
TI  - Priming Mesenchymal Stem Cells with Endothelial Growth Medium Boosts Stem Cell
      Therapy for Systemic Arterial Hypertension.
AB  - Systemic arterial hypertension (SAH), a clinical syndrome characterized by
      persistent elevation of arterial pressure, is often associated with abnormalities
      such as microvascular rarefaction, defective angiogenesis, and endothelial
      dysfunction. Mesenchymal stem cells (MSCs), which normally induce angiogenesis
      and improve endothelial function, are defective in SAH. The central aim of this
      study was to evaluate whether priming of MSCs with endothelial growth medium (EGM
      2) increases their therapeutic effects in spontaneously hypertensive rats (SHRs).
      Adult female SHRs were administered an intraperitoneal injection of vehicle
      solution (n = 10), MSCs cultured in conventional medium (DMEM plus 10% FBS, n =
      11), or MSCs cultured in conventional medium followed by 72 hours in EGM-2 (pMSC,
      n = 10). Priming of the MSCs reduced the basal cell death rate in vitro. The
      administration of pMSCs significantly induced a prolonged reduction (10 days) in
      arterial pressure, a decrease in cardiac hypertrophy, an improvement in
      endothelium-dependent vasodilation response to acetylcholine, and an increase in
      skeletal muscle microvascular density compared to the vehicle and MSC groups. The
      transplanted cells were rarely found in the hearts and kidneys. Taken together,
      our findings indicate that priming of MSCs boosts stem cell therapy for the
      treatment of SAH. 

PMID- 26300925
TI  - SDF-1/CXCR4 Axis Promotes MSCs to Repair Liver Injury Partially through Trans
      Differentiation and Fusion with Hepatocytes.
AB  - MSCs have become a popular target for developing end-stage liver therapies. In
      this study, two models of bone marrow chimeric mice were used to construct the
      liver failure models. Then it was found that MSCs can transdifferentiate into
      hepatocyte-like cells and these hepatocyte-like cells can significantly express
      albumin. Furthermore it was also found that MSCs can fuse with the hepatocytes
      and these cells had the proliferation activity. However, the percentage of
      transdifferentiation was significantly higher than fusion. So it was considered
      that MSCs which transdifferentiated into hepatocyte-likes cells played important
      roles for repairing the injuring liver function. 

PMID- 26300926
TI  - Anaphylaxis Preparedness among Preschool Staff before and after an Educational
      Intervention.
AB  - Introduction. Children with severe food allergies may spend many hours in the
      preschool setting. Little is known about anaphylaxis recognition and management
      preparedness among preschool staff. The objective of this study was to assess
      anaphylaxis preparedness among preschool staff. Methods. Anonymous questionnaires
      were administered before and after a 40-minute educational seminar on anaphylaxis
      recognition and management. Results. In total, 181 individuals participated in
      the preintervention survey and 171 participated in the postintervention survey.
      The comfort level with recognizing anaphylaxis and administering an epinephrine
      autoinjector significantly increased after the intervention (P < .001 for both).
      Of the 5 steps needed to administer an epinephrine autoinjector, staff named a
      mean (SD) of 3 (1.3) steps in the correct order compared with 4.2 (1.1) steps
      after the educational intervention (P < .001). Conclusion. This study shows that
      a brief education intervention can significantly increase caregiver comfort
      regarding identifying anaphylaxis and administering an epinephrine autoinjector. 

PMID- 26300924
TI  - Cell Therapy in Patients with Critical Limb Ischemia.
AB  - Critical limb ischemia (CLI) represents the most advanced stage of peripheral
      arterial obstructive disease (PAOD) with a severe obstruction of the arteries
      which markedly reduces blood flow to the extremities and has progressed to the
      point of severe rest pain and/or even tissue loss. Recent therapeutic strategies
      have focused on restoring this balance in favor of tissue survival using
      exogenous molecular and cellular agents to promote regeneration of the
      vasculature. These are based on stimulation of angiogenesis by extracellular and
      cellular components. This review article carries out a systematic analysis of the
      most recent scientific literature on the application of stem cells in patients
      with CLI. The results obtained from the detailed analysis of the recent
      literature data have confirmed the beneficial role of cell therapy in reducing
      the rate of major amputations in patients with CLI and improving their quality of
      life. 

PMID- 26300927
TI  - Consensus communication on early peanut introduction and the prevention of peanut
      allergy in high-risk infants.
AB  - The purpose of this brief communication is to highlight emerging evidence to
      existing guidelines regarding potential benefits of supporting early, rather than
      delayed, peanut introduction during the period of complementary food ntroduction
      in infants. This document should be considered as interim guidance based on
      consensus among the following organizations: American Academy of Allergy, Asthma
      & Immunology; American Academy of Pediatrics; American College of Allergy, Asthma
      & Immunology; Australasian Society of Clinical Immunology and Allergy; Canadian
      Society of Allergy and Clinical Immunology; European Academy of Allergy and
      Clinical Immunology; Israel Association of Allergy and Clinical Immunology;
      Japanese Society for Allergology; Society for Pediatric Dermatology; and World
      Allergy Organization. More formal guidelines regarding early-life, complementary
      feeding practices and the risk of allergy development will follow in the next
      year from the National Institute of Allergy and Infectious Diseases - sponsored
      Working Group and the European Academy of Allergy and Clinical Immunology. 

PMID- 26300923
TI  - Stem Cells and Regenerative Medicine: Myth or Reality of the 21th Century.
AB  - Since the 1960s and the therapeutic use of hematopoietic stem cells of bone
      marrow origin, there has been an increasing interest in the study of
      undifferentiated progenitors that have the ability to proliferate and
      differentiate into various tissues. Stem cells (SC) with different potency can be
      isolated and characterised. Despite the promise of embryonic stem cells, in many
      cases, adult or even fetal stem cells provide a more interesting approach for
      clinical applications. It is undeniable that mesenchymal stem cells (MSC) from
      bone marrow, adipose tissue, or Wharton's Jelly are of potential interest for
      clinical applications in regenerative medicine because they are easily available
      without ethical problems for their uses. During the last 10 years, these
      multipotent cells have generated considerable interest and have particularly been
      shown to escape to allogeneic immune response and be capable of immunomodulatory
      activity. These properties may be of a great interest for regenerative medicine.
      Different clinical applications are under study (cardiac insufficiency,
      atherosclerosis, stroke, bone and cartilage deterioration, diabetes, urology,
      liver, ophthalmology, and organ's reconstruction). This review focuses mainly on
      tissue and organ regeneration using SC and in particular MSC. 

PMID- 26300928
TI  - YMDD Motif Mutation Profile Among Patients Receiving Liver Transplant Due to
      Hepatitis B Virus Infection With Long Term Lamivudine/Immunoglobulin Therapy.
AB  - BACKGROUND: Recurrence of Hepatitis B Virus infection in patients undergoing
      liver transplanted (LT) is a serious and often fatal problem. Lamivudine (LAM)
      and Hepatitis B Immunoglobulin (HBIG) are widely used to manage hepatitis B
      recurrence after liver transplantation. However, the outcomes in patients are
      less elucidated. OBJECTIVES: The current study aimed to evaluate the YMDD motif
      mutations profile among the patients undergoing LT infected with HBV and treated
      with LAM/HBIG at least for one year. PATIENTS AND METHODS: Thirty patients with
      liver transplantation due to HBV were enrolled, while DNA level remained under
      detection limit of 50 IU/mL before transplantation and abnormal higher levels of
      liver enzymes after LT. The HBV genome detection was performed by two different
      Polymerase Chain Reaction methods following viral quantification by commercial
      Real-Time PCR. HbsAg detection, besides liver function tests were conducted as
      complementary assays. To assess nucleotide analogue mutations, the major part of
      polymerase gene (aa 80 - 240) was amplified by Nested-PCR, introduced to
      sequencing and subjected to phylogenetic analysis. RESULTS: Totally, according to
      the laboratory criteria there were 13 cases with detectable HBV genome, while the
      mean liver enzyme levels were higher in recurrent patients and HBsAg was detected
      only in four out of the 13 cases. Phylogenetic analysis demonstrated that all
      isolated genomes belonged to genotype D. Critical M204I mutation, as a proof for
      resistance to LAM, was detected among 46% of the subjects and natural entecavir
      resistance (S202I) was also distinguished in one subject. Viral quantification
      showed higher titer in LAM resistant group in comparison to the group with
      undetectable drug resistance mutant (P > 0.05). CONCLUSIONS: Although the
      patients carrying M204I mutation were more likely to show lack of responses to
      LAM therapy, LAM replacing by other nucleoside/tide analogs plus HBIG maybe still
      effective in decreasing hepatitis B recurrence after liver transplantation.
      However, it is suggested that drug resistance test should be considered by
      clinicians during therapeutic management to avoid the following viral
      breakthrough.

PMID- 26300929
TI  - Prevalence and Risk Factors of HCV/HIV Co-Infection and HCV Genotype Distribution
      in North-Eastern Poland.
AB  - BACKGROUND: HIV/HCV co-infection predisposes to accelerated liver damage and
      increased both liver-related and unrelated morbidity and mortality in patients
      with HIV infection. OBJECTIVES: The aim of this study was to evaluate the
      prevalence of HCV infection, seropositivity, risk factors and genotype
      distribution among treated HIV positive patients. Furthermore, the occurrence and
      causes of deaths were analyzed. PATIENTS AND METHODS: Adult HIV-1 infected
      patients, with at least one antiHCV result, treated in one of Polish HIV/AIDS
      reference centers, participated in this cross-sectional study. RESULTS: Four
      hundred and fifty seven patients with a median age of 38 years (ranged 23 - 72),
      and predominantly male (76.6%) were enrolled in the study. Anti-HCV antibodies
      were detected in 325 individuals (71.1%). HCV RNA was detected in 207 of the 233
      patients tested (88%). The HCV genotype analysis (n = 193) demonstrated almost
      equal distribution with slight genotype 1 domination as 37.3%, mainly 1b,
      followed by genotypes 3 as 32.1% and 4 as 30.6%. No association was found between
      HCV genotype and route of HIV acquisition. In univariate analysis, higher HCV
      seropositivity was related to male sex, intravenous drug use (IDU), mode of HIV
      transmission, history of drug and alcohol abuse and imprisonment. In multivariate
      analysis, only being injection drug user (P = 0.0001), imprisonment (P = 0.310)
      and younger age at the HIV diagnosis per each year (P = 0.025) were identified as
      risk factors for HCV infection. Sixty three deaths were reported; no association
      was found between HCV seropositivity and death prevalence. CONCLUSIONS: HIV/HCV
      co-infection is an important medical problem in North-Eastern Poland. A history
      of incarceration and younger age at HIV diagnosis were additional to IDU risk
      factors for HCV seropositivity in this cohort.

PMID- 26300930
TI  - Impact of the IL-10 Promoter Gene Polymorphisms in the Severity of Chronic
      Hepatitis B Infection.
AB  - BACKGROUND: Interleukin-10 (IL-10) is an important anti-inflammatory cytokine.
      The polymorphisms of its promoter gene have been considered to be related with
      the chronicity of hepatitis B infection. OBJECTIVES: The aim of this study was to
      evaluate the polymorphisms at different positions in the IL-10 promoter gene in
      patients with chronic hepatitis B. PATIENTS AND METHODS: Totally, 166 patients
      with chronic hepatitis B infection were enrolled. Genotypes at different
      positions (i.e. -819, - 592, and - 1082) in the IL-10 gene promoter were
      determined. RESULTS: The C/A genotype at position -592, C/T genotype at position 
      819, and GCC/ATA haplotype of the IL-10 gene promoter were significantly more
      common in the patients with cirrhosis. The genotypes were significantly different
      between the hepatitis B e antigen (HBeAg)-negative and HBeAg-positive patients at
      position -592 (C/A and C/C), position -819 (C/C and C/T), and position -1082 (A/A
      and G/A). CONCLUSIONS: Some IL-10 promoter gene polymorphisms predisposed the
      infected hepatitis B virus cases to cirrhosis in our study population.

PMID- 26300931
TI  - Performance of Protein Induced by Vitamin K Absence or Antagonist-II (PIVKA-II)
      for Hepatocellular Carcinoma Screening in Chinese Population.
AB  - BACKGROUND: Alpha-fetoprotein (AFP) has long been used as an effective biomarker
      for hepatocellular carcinoma (HCC) screening; however, not all HCC patients can
      be detected with an elevated AFP level, especially in early HCC patients. Protein
      Induced by vitamin K absence or antagonist-II (PIVKA-II) is another serum
      biomarker linked to HCC; however, sensitivity and specificity remain
      controversial and data in Chinese groups is even rarer. OBJECTIVES: To evaluate
      the performance of PIVKA-II alone and combined with AFP in HCC screening in
      Chinese population. PATIENTS AND METHODS: This retrospective study enrolled 150
      HCC patients in Southwest Hospital, of which 16 patients were excluded due to
      lack of basic information. A total of 347 patients with hepatitis B, 105 with non
      HCC cancers and 53 healthy people were enrolled as controls. Levels of AFP and
      PIVKA-II were measured by chemiluminescence enzyme immunoassay (CLEIA) and
      chemiluminescent microparticle Immunoassay (CMIA), respectively. RESULTS: The
      sensitivity and specificity of PIVKA-II were 74.6% and 67.8% at a cutoff of 40
      mAU/mL and 64.2% and 89.7% at a cutoff of 200 mAU/mL. The sensitivity and
      specificity of AFP were 76.7% and 65.0% at a cutoff of 20 ng/mL and 60.4% and
      88.9% at a cutoff of 195.23 ng/mL. The combination of two markers had a
      sensitivity and specificity of 91.1% and 41.0%, respectively. The area under the
      receiving operating curve (AUROC) for PIVKA-II (0.756, 95% confidence interval,
      CI: 0.695 - 0.816) was less than the AUROC for AFP (0.823, 95% CI: 0.780 -
      0.865), and in combination, the AUROC increased to 0.843 (95% CI: 0.801 - 0.885).
      CONCLUSIONS: PIVKA-II was as efficient as AFP when used as a single marker for
      HCC screening and the combination of two biomarkers gave a better performance.

PMID- 26300932
TI  - Hepatitis C Virus Treatment Revolution: Eastern European Story.
AB  - Hepatitis C can be cured and even eradicated by new "revolutionary" treatments.
      However, at present exorbitant prices, Eastern European countries cannot afford
      the new treatments, while in western rich and developed countries (e.g. Germany
      and France) they are already available. Concerted efforts of governments, public
      health officials, and the community at large, are needed to negotiate agreements
      with pharmaceuticals companies to make the new treatments accessible and
      affordable. When science has demonstrated that hepatitis C can be cured, it would
      be unforgivable if millions of infected patients from eastern parts of the
      continent were denied access to new treatment on grounds of high prices and
      financial constraints. 

PMID- 26300933
TI  - Efficacy of Hepatoprotective Agents With or Without Antiviral Drugs on Liver
      Function and Fibrosis in Patients With Hepatitis B: A Meta-Analysis.
AB  - CONTEXT: To systematically evaluate the effects of hepatoprotective agents, when
      delivered either alone or in combination with other antiviral or non-antiviral
      drugs in patients with hepatitis B and hepatic fibrosis. OBJECTIVES: The current
      randomized controlled clinical trials aimed to evaluate the efficacy of
      combinations of antiviral and non-antiviral hepatoprotective agents on indexes of
      liver function and liver fibrosis in patients with hepatitis B. DATA SOURCES:
      Published literatures in Chinese and English on hepatoprotective treatment
      strategies for chronic hepatitis B and liver fibrosis were searched in three
      databases and randomized controlled clinical trials were selected. STUDY
      SELECTION: Data were extracted according to a variety of inclusion and exclusion
      criteria. Meta-analysis was employed to analyze the data. RESULTS: A total of 22
      randomized controlled trials encompassing 1,714 cases were considered in the meta
      analysis. The obtained results indicated that the combination of antiviral drug
      and hepatoprotective agent was better than antiviral drug alone to improve liver
      function. Similarly, regarding liver fibrosis, using two different
      hepatoprotective agents was better than using one agent. The normalization rates
      of Aminotransferase (ALT) and total Bilirubin (TBil) were improved 25.7% by two
      hepatoprotective agents compared to the single agent. Acetylcysteine was superior
      to ursodeoxycholic acid or silibinin to reduce ALT. Ursodeoxycholic acid was
      superior to acetylcysteine or silibinin to reduce TBIL. CONCLUSIONS:
      Hepatoprotective agents combined with antiviral drugs can significantly improve
      liver function and liver fibrosis parameters in patients with hepatitis B.

PMID- 26300934
TI  - Parathyroid Hormone Levels May Predict Nonalcoholic Steatohepatitis in Morbidly
      Obese Patients.
AB  - BACKGROUND: Obesity as a worldwide health problem is associated with nonalcoholic
      steatohepatitis (NASH). Since severe liver injury may be present in asymptomatic
      obese patients and a definite diagnosis of nonalcoholic steatohepatitis can only
      be made after an invasive procedure of liver biopsy, there is a need for
      noninvasive methods to predict the probability of NASH. OBJECTIVES: To
      investigate the role of vitamin D endocrine system in predicting the probability
      of presence of NASH in asymptomatic morbidly obese candidates of bariatric
      surgery. PATIENTS AND METHODS: From December 09 to March 11, every patient
      undergoing bariatric surgery had a liver biopsy. Nonalcoholic steatohepatitis was
      diagnosed using the Lee's criteria, the baseline labs obtained and the
      association between laboratory data and presence of NASH assessed. RESULTS: Forty
      six patients (34 women, aged 36.5 +/- 10.6 years) were analyzed. The mean levels
      of liver enzymes were significantly higher in the group with NASH (P value <
      0.01). In an unadjusted logistic model, PTH was the only variable in vitamin D
      endocrine system which was significantly associated with NASH (odds ratio (OR):
      1.04, 95%CI: 1.01 - 1.07). After adjustment for possible confounding factors, age
      (OR: 1.22, 95%CI: 1.00 - 1.50) and PTH (OR: 1.08, 95%CI: 1.01 - 1.16) were
      predictive factors for NASH (P value < 0.05). CONCLUSIONS: Elevated serum PTH
      level was the predictive factor for NASH in morbidly obese patients. Also, we
      reported elevated serum liver enzymes, high serum PTH levels and older age as
      predictors of NASH in patients seeking obesity surgical treatments.

PMID- 26300935
TI  - Diagnostic Value of Arginase-1 and Glypican-3 in Differential Diagnosis of
      Hepatocellular Carcinoma, Cholangiocarcinoma and Metastatic Carcinoma of Liver.
AB  - BACKGROUND: Hepatocellular carcinoma is the most common primary liver cancer.
      Pathologic distinction between Hepatocellular Carcinoma (HCC) and adenocarcinoma
      (Cholangiocarcinoma (CC) and Metastatic Adenocarcinoma (MA)) can be challenging
      and sometimes requires immunohistochemical panels. Recently, Arginase-1 (ARG-1)
      and Glypican-3 (GPC-3) have been introduced for differentiation of these tumors.
      OBJECTIVES: The aim of this study was to determine the diagnostic accuracy of ARG
      1 and GLP-3 in differential diagnosis of liver tumors. PATIENTS AND METHODS:
      Eighty-nine formalin-fixed paraffin-embedded tissue blocks including 43 cases of
      documented HCCs, 19 cases of documented CC, and 27 cases of MA involving the
      liver (15 colon, 5 stomach, 3 pancreas, 2 gallbladder, 1 duodenum and 1 ampulla
      of vater) were evaluated for immunohistochemical expression of ARG-1 and GPC-3.
      RESULTS: Arginase-1 and GPC-3 demonstrated diffuse staining, as reactivity in >
      97% of HCCs, whereas only one (5.3%) and 2 (10.5%) of 19 CC cases show positive
      staining for GPC-3 and ARG-1, respectively. The expression of both markers in MA
      showed 6 (22.2%) for ARG-1 and 3 (11.1%) for GPC-3, especially with colorectal
      origin. Our findings showed a statistically significant difference between ARG-1
      and GPC-3 expression in HCC, CC and MA. CONCLUSIONS: The findings of this study
      reveal that both ARG-1 and GPC-3 are helpful IHC markers to separate HCC from CC
      and MA. Furthermore, ARG-1 shows 100% sensitivity and 82.6% specificity for the
      diagnosis of HCC whereas GPC-3 demonstrated 97.7% sensitivity and 91.3%
      specificity for the diagnosis of this tumor.

PMID- 26300936
TI  - Impact of Hepatitis C Virus Infection on Cognitive Function in Patients With
      Covert Hepatic Encephalopathy.
AB  - BACKGROUND: Liver cirrhosis has a significant impact on patient's quality of life
      and socioeconomic status and is associated with increased susceptibility to
      vehicle accidents and falls. OBJECTIVES: This study was conducted to evaluate
      cognitive function in patients with cirrhosis. PATIENTS AND METHODS: All
      subjects, who underwent transient elastography (TE) between March 2014 and August
      2014 in Shariati outpatient clinic, Tehran, Iran, were enrolled in the study. The
      diagnosis of cirrhosis was made based on clinical and laboratory findings and
      liver stiffness measurement (LSM) values > 14. Wechsler Memory Scale (WMS) and
      simple visual reaction time (RT) were the neuropsychiatric tests used to assess
      cognitive function, in all subjects. RESULTS: A total of 37 cirrhotic patients
      and 37 matched controls were included. Patients with cirrhosis had significantly
      lower mean quotient (MQ) score, compared with controls (91 +/- 18.2 vs. 114.6 +/-
      17.5, P <0.001). All of WMS subscales, except associate learning, showed
      statistically significant differences between the two groups. Reaction time was
      more prolonged in patients with cirrhosis, compared with controls. Cognitive
      function of hepatitis C virus (HCV) patients was significantly impaired, with
      respect to logical memory, visual reproduction and MQ score, compared to other
      underlying causes of cirrhosis (P = 0.01, P = 0.04, and P = 0.01, respectively).
      CONCLUSIONS: Our results suggested that neuropsychiatric and cognitive problems
      must be considered in the management of covert hepatic encephalopathy (HE)
      patients, especially in patients with HCV infection. The WMS and simple visual RT
      tests are useful methods for the early diagnosis of covert HE.

PMID- 26300937
TI  - Complement regulation: physiology and disease relevance.
AB  - The complement system is part of the innate immune response and as such defends
      against invading pathogens, removes immune complexes and damaged self-cells, aids
      organ regeneration, confers neuroprotection, and engages with the adaptive immune
      response via T and B cells. Complement activation can either benefit or harm the
      host organism; thus, the complement system must maintain a balance between
      activation on foreign or modified self surfaces and inhibition on intact host
      cells. Complement regulators are essential for maintaining this balance and are
      classified as soluble regulators, such as factor H, and membrane-bound
      regulators. Defective complement regulators can damage the host cell and result
      in the accumulation of immunological debris. Moreover, defective regulators are
      associated with several autoimmune diseases such as atypical hemolytic uremic
      syndrome, dense deposit disease, age-related macular degeneration, and systemic
      lupus erythematosus. Therefore, understanding the molecular mechanisms by which
      the complement system is regulated is important for the development of novel
      therapies for complement-associated diseases. 

PMID- 26300938
TI  - Clinical risk factors associated with the development of wheezing in children
      less than 2 years of age who required hospitalization for viral lower respiratory
      tract infections.
AB  - PURPOSE: Wheezing following viral lower respiratory tract infections (LRTIs) in
      children <2 years of age is an important risk factor for the development of
      asthma later in life; however, not all children with viral LRTIs develop
      wheezing. This study investigated risk factors for the development of wheezing
      during viral LRTIs requiring hospitalization. METHODS: The study included 142
      children <2 years of age hospitalized for LRTIs with at least one virus
      identified as the cause and classified them into children diagnosed with LRTIs
      with wheezing (n=70) and those diagnosed with LRTIs without wheezing (n=72).
      RESULTS: There were no significant differences in the viruses detected between
      the two groups. Multivariate logistic regression analysis showed that, after
      adjusting for potentially confounding variables including sex and age, the
      development of wheezing was strongly associated with parental history of allergic
      diseases (adjusted odds ratio [aOR], 20.19; 95% confidence interval [CI], 3.22
      126.48), past history of allergic diseases (aOR, 13.95; 95% CI, 1.34-145.06),
      past history of hospitalization for respiratory illnesses (aOR, 21.36; 95% CI,
      3.77-120.88), exposure to secondhand smoke at home (aOR, 14.45; 95% CI, 4.74
      44.07), and total eosinophil count (aOR, 1.01; 95% CI, 1.01-1.02). CONCLUSION:
      Past and parental history of allergic diseases, past history of hospitalization
      for respiratory illnesses, exposure to secondhand smoke at home, and total
      eosinophil count were closely associated with the development of wheezing in
      children <2 years of age who required hospitalization for viral LRTIs. Clinicians
      should take these factors into consideration when treating, counseling, and
      monitoring young children admitted for viral LRTIs.

PMID- 26300939
TI  - Applying the bacterial meningitis score in children with cerebrospinal fluid
      pleocytosis: a single center's experience.
AB  - PURPOSE: The widespread introduction of bacterial conjugate vaccines has
      decreased the risk of cerebrospinal fluid (CSF) pleocytosis due to bacterial
      meningitis (BM) in children. However, most patients with CSF pleocytosis are
      hospitalized and treated with parenteral antibiotics for several days. The
      bacterial meningitis score (BMS) is a validated multivariate model derived from a
      pediatric population in the postconjugate vaccine era and has been evaluated in
      several studies. In the present study, we examined the usefulness of BMS in South
      Korean patients. METHODS: This study included 1,063 patients with CSF pleocytosis
      aged between 2 months and 18 years. The BMS was calculated for all patients, and
      the sensitivity and negative predictive value (NPV) of the test were evaluated.
      RESULTS: Of 1,063 patients, 1,059 (99.6%) had aseptic meningitis (AM). Only four
      patients (0.4%) had BM. The majority of patients (98%) had a BMS of <=1,
      indicating a diagnosis of AM. The BMS was 0 in 635 patients (60%) and 1 in 405
      patients (38%). All four BM patients had a BMS of >=4. CONCLUSION: To our
      knowledge, this is the first study to investigate the diagnostic strength of the
      BMS in South Korea. In our study, the BMS showed 100% sensitivity and 100% NPV.
      Therefore, we believe that the BMS is a good clinical prediction rule to identify
      children with CSF pleocytosis who are at a risk of BM.

PMID- 26300940
TI  - The strong association of left-side heart anomalies with Kabuki syndrome.
AB  - PURPOSE: Kabuki syndrome is a multiple congenital malformation syndrome, with
      characteristic facial features, mental retardation, and skeletal and congenital
      heart anomalies. However, the cardiac anomalies are not well described in the
      Korean population. We analyzed the cardiac anomalies and clinical features of
      Kabuki syndrome in a single tertiary center. METHODS: A retrospective analysis
      was conducted for a total of 13 patients with Kabuki syndrome. RESULTS: The
      median age at diagnosis of was 5.9 years (range, 9 days to 11 years and 8
      months). All patients showed the characteristic facial dysmorphisms and
      congenital anomalies in multiple organs, and the diagnosis was delayed by 5.9
      years (range, 9 days to 11 years and 5 months) after the first visit. Noncardiac
      anomalies were found in 84% of patients, and congenital heart diseases were found
      in 9 patients (69%). All 9 patients exhibited left-side heart anomalies,
      including hypoplastic left heart syndrome in 3, coarctation of the aorta in 4,
      aortic valve stenosis in 1, and mitral valve stenosis in 1. None had right-side
      heart disease or isolated septal defects. Genetic testing in 10 patients revealed
      9 novel MLL2 mutations. All 11 patients who were available for follow-up
      exhibited developmental delays during the median 4 years (range, 9 days to 11
      years 11 months) of follow-up. The leading cause of death was hypoplastic left
      heart syndrome. CONCLUSION: Pediatric cardiologist should recognize Kabuki
      syndrome and the high prevalence of left heart anomalies with Kabuki syndrome.
      Genetic testing can be helpful for early diagnosis and counseling.

PMID- 26300941
TI  - The corrected QT (QTc) prolongation in hyperthyroidism and the association of
      thyroid hormone with the QTc interval.
AB  - PURPOSE: Ventricular repolarization is assessed using the QT interval corrected
      by the heart rate (QTc) via an electrocardiogram (ECG). Prolonged QTc is
      associated with an increased risk of arrhythmias and cardiac mortality. As there
      have been few reports regarding the effects of hyperthyroidism on ventricular
      repolarization, we studied the association between serum free thyroxine (free T4
      [fT4]) and thyroid stimulating hormone (TSH) levels and the QTc interval.
      METHODS: Thirty-eight patients with hyperthyroidism (<30 years old) were
      included, and we used their clinical records and available ECGs (between August
      2003 and August 2011) to evaluate the association between their fT4 and TSH
      levels and their QTc interval. In addition, we studied the ECGs of 72 age-matched
      patients with no hyperthyroidism (control group) and compared their data with
      that from the patients group. RESULTS: The QTc duration in patients with
      hyperthyroidism was significantly prolonged compared to that in the control
      subjects (P<0.001). In addition, the number of hyperthyroid patients with
      abnormal prolonged QTc was significantly higher than that in the control group
      (P<0.001). Among the patients with hyperthyroidism, patients with prolonged QTc
      and borderline QTc had higher fT4 levels and there was positive correlation
      between their fT4 levels and their QTc interval (P<0.05). However, no correlation
      was observed between their TSH levels and their QTc interval. CONCLUSION: We
      report that hyperthyroidism is associated with QTc prolongation. The correlation
      between the fT4 levels and the QTc interval suggests that thyroid status is
      associated with QTc values and the risk of cardiac mortality.

PMID- 26300942
TI  - Graves disease following rabbit antithymocyte globulin treatment of severe
      aplastic anemia in a Korean child.
AB  - Antithymocyte globulin (ATG) is used as an immunosuppressive treatment (IST) to
      deplete clonal suppressor T cells in patients with severe aplastic anemia (SAA).
      The depletion of suppressor T cells by ATG may affect the activation of B cells,
      which results in an increased risk for autoimmune conditions. A 12-year-old boy
      was diagnosed with idiopathic SAA. As he did not have an human leukocyte antigen
      matched sibling, he was treated with rabbit ATG (3.5 mg/kg/day for 5 days) and
      cyclosporine. Five months later, he became transfusion independent. However, 23
      months after IST, he complained of mild hand tremors, sweating, weight loss,
      palpitations, and goiter. Results of thyroid function tests revealed
      hyperthyroidism (free thyroxine, 3.42 ng/dL; thyroid stimulating hormone [TSH],
      <0.01 nIU/mL; triiodothyronine, 3.99 ng/mL). Results of tests for autoantibodies
      were positive for the antimicrosome antibody and TSH-binding inhibitory
      immunoglobulin, but negative for the antithyroglobulin antibody and antinuclear
      antibody. He was treated with methimazole, and his symptoms improved. The patient
      has been disease free for 39 months after IST and 9 months after methimazole
      treatment. This case report suggests that although rare, rabbit ATG may have
      implications in the pathogenesis of autoimmune hyperthyroidism. Our findings
      suggest that thyroid function tests should be incorporated in the routine follow
      up of SAA patients treated with ATG. 

PMID- 26300943
TI  - Hypopituitarism and Legg-Calve-Perthes disease related to difficult delivery.
AB  - Legg-Calve-Perthes (LCP) disease is characterized by idiopathic avascular
      osteonecrosis of the epiphysis of the femur head. The main factor that plays a
      role in the etiology of the disease is decreased blood flow to the epiphysis.
      Many predisposing factors have been suggested in the etiology of LCP disease, and
      most have varying degrees of effects. Here we present the case of a boy aged 4
      years and 10 months with complaints of short stature and a diagnosis of multiple
      hypophyseal hormone deficiency, in whom LCP disease and difficult birth-related
      pituitary stalk interruption syndrome were identified by anamnesis. The present
      case revealed that LCP disease and hypophyseal hormone deficiency could be
      secondary to difficult birth and that LCP disease could be secondary to insulin
      like growth factor 1 deficiency. Additionally, to the best of our knowledge there
      is no published case on the relation between LCP disease and insulin-like growth
      factor 1 deficiency. Therefore, we believe that this case is worthy of
      presentation. 

PMID- 26300944
TI  - Acupoint Sensitization, Acupuncture Analgesia, Acupuncture on Visceral Functional
      Disorders, and Its Mechanism.

PMID- 26300945
TI  - Efficacy and Safety of Sanfu Herbal Patch at Acupoints for Persistent Allergic
      Rhinitis: Study Protocol for a Randomized Controlled Trial.
AB  - Background. The Sanfu herbal patch (SHP) has been widely used to treat allergic
      rhinitis (AR) in China. SHP has been reported to be effective for managing the
      symptoms of AR, but the evidence suffers from methodological limitations.
      Therefore, we designed a three-armed, randomized, and placebo-controlled trial to
      evaluate the efficacy and safety of SHP for persistent allergic rhinitis (PAR).
      Methods. The trial consists of 5 treatment sessions along with a one-year follow
      up. This process is then repeated in the second and third years. Eligible
      participants diagnosed with PAR were randomized at a ratio of 2 : 2 : 1 into one
      of three groups: (a) SHP group; (b) placebo group; or (c) waiting-list group. The
      waiting-list group will receive no treatment in the first year but will receive
      SHP in the following two years. The primary outcome, total nasal symptoms score,
      is self-assessed at the beginning of each treatment session and during each
      annual follow-up. Secondary outcomes include the Rhinoconjunctivitis Quality-of
      Life Questionnaire, allergic rhinitis attacks, and relief medications. The trial
      will be stopped if early termination criteria are met during the interim
      analysis. Ethics. This protocol has been approved by site ethics committee
      (number B2014-014-01) and is registered with ClinicalTrials.gov NCT02192645. 

PMID- 26300946
TI  - Anti-Inflammatory Property of Plantago major Leaf Extract Reduces the
      Inflammatory Reaction in Experimental Acetaminophen-Induced Liver Injury.
AB  - Hepatic injury induces inflammatory process and cell necrosis. Plantago major is
      traditionally used for various diseases. This study aimed to determine the anti
      inflammatory property of P. major leaf extracts on inflammatory reaction
      following acetaminophen (APAP) hepatotoxicity. Thirty male Sprague-Dawley rats
      were divided into 5 groups, namely, normal control (C), APAP, aqueous (APAP +
      AQ), methanol (APAP + MT), and ethanol (APAP + ET) extract treated groups. All
      APAP groups received oral APAP (2 g/kg) at day 0. Then, 1000 mg/kg dose of P.
      major extracts was given for six days. The levels of liver transaminases were
      measured at day 1 and day 7 after APAP induction. At day 7, the blood and liver
      tissue were collected to determine plasma cytokines and tissue 11beta-HSD type 1
      enzyme. The in vitro anti-inflammatory activities of methanol, ethanol, and
      aqueous extracts were 26.74 +/- 1.6%, 21.69 +/- 2.81%, and 12.23 +/- 3.15%,
      respectively. The ALT and AST levels were significantly higher in the APAP groups
      at day 1 whereas the enzyme levels of all groups showed no significant difference
      at day 7. The extracts treatment significantly reduced the proinflammatory
      cytokine levels and significantly increased the 11beta-HSD type 1 enzyme activity
      (p < 0.05). In conclusion, the P. major extracts attenuate the inflammatory
      reaction following APAP-induced liver injury. 

PMID- 26300947
TI  - Oral Administration of Ganoderma lucidum to Lead-Exposed Rats Protects
      Erythrocytes against Hemolysis: Implicates to Anti-Anemia.
AB  - We studied the effect of chronic oral exposure to lead acetate (PbA) on the
      sensitivity of RBC to hemolysis and whether the sensitivity could be decreased by
      feeding the rats with extract of medicinal mushroom Ganoderma lucidum. Three
      groups of rats, control, PbA-exposed, and G. lucidum (Gl)+PbA, were used. PbA (3
      mM) was administered via drinking water and G. lucidum extract by gavage at 300
      mg/Kg BW/day for 12 weeks. Afterwards, the rats were killed and washed RBCs were
      subjected to hemolysis in the presence of Fenton's reagents. Hemolysis was
      determined by estimating the amount of released hemoglobin. The levels of lipid
      peroxide (LPO) and GSH were determined from RBC membranes and whole RBCs,
      respectively. The levels of TNFalpha and LPO also were determined from hepatic
      tissues. The RBCs of PbA-exposed rats displayed significantly higher sensitivity
      to hemolysis than those of the Gl+PbA rats. The levels of LPO increased and GSH
      decreased in the RBCs, with concomitant increases in the levels of hepatic
      TNFalpha and LPO in the PbA-exposed rats. The degree of hemolysis was
      significantly low in the RBCs of Gl+PbA rats, concurrently with amelioration of
      hepatic parameters. Finally, the study suggests that PbA-induced-hemolysis and
      related oxidative-toxicity might be minimized by consumption of G. lucidum. 

PMID- 26300949
TI  - ROS evaluation for a series of CNTs and their derivatives using an ESR method
      with DMPO.
AB  - Carbon nanotubes (CNTs) are important materials in advanced industries. It is a
      concern that pulmonary exposure to CNTs may induce carcinogenic responses. It has
      been recently reported that CNTs scavenge ROS though non-carbon fibers generate
      ROS. A comprehensive evaluation of ROS scavenging using various kinds of CNTs has
      not been demonstrated well. The present work specifically investigates ROS
      scavenging capabilities with a series of CNTs and their derivatives that were
      physically treated, and with the number of commercially available CNTs. CNT
      concentrations were controlled at 0.2 through 0.6 wt%. The ROS scavenging rate
      was measured by ESR with DMPO. Interestingly, the ROS scavenging rate was not
      only influenced by physical treatments, but was also dependent on individual
      manufacturing methods. Ratio of CNTs to DMPO/ hydrogen peroxide is a key
      parameter to obtain appropriate ROS quenching results for comparison of CNTs. The
      present results suggest that dangling bonds are not a sole factor for scavenging,
      and electron transfer on the CNT surface is not clearly determined to be the sole
      mechanism to explain ROS scavenging.

PMID- 26300950
TI  - beta carbonic anhydrase is required for female fertility in Drosophila
      melanogaster.
AB  - BACKGROUND: Carbonic anhydrases (CAs, EC 4.2.1.1) are ubiquitous enzymes that
      catalyze the reversible hydration reaction of carbon dioxide. CAs are present as
      six structurally divergent enzyme families: alpha, beta, gamma, delta, zeta and
      eta. beta-CAs have a wide distribution across different species including
      invertebrates. Previously, we showed that Drosophila melanogaster beta-CA is a
      highly active mitochondrial enzyme. In this study, we investigated the function
      of Drosophila beta-CA by silencing the expression of the beta-CA gene using
      UAS/GAL4-based RNA interference (RNAi) in Drosophila in vivo. RESULTS: Crossing
      beta-CA RNAi lines over ubiquitous Actin driver flies did not produce any viable
      progeny, indicating that beta-CA expression is required for fly development. RNAi
      silencing of beta-CA ubiquitously in adult flies did not affect their survival
      rate or function of mitochondrial electron transport chain. Importantly, beta-CA
      RNAi led to impaired reproduction. All beta-CA knockdown females were sterile,
      and produced few or no eggs. Whole ovaries of knockdown females looked normal but
      upon cadherin staining, there was an apparent functional defect in migration of
      border cells, which are considered essential for normal fertilization.
      CONCLUSIONS: These results indicate that although Drosophila beta-CA is
      dispensable for survival of adult flies, it is essential for female fertility.

PMID- 26300948
TI  - Low prevalence of human leukocyte antigen-B*5701 in HIV-1-infected Chinese
      subjects: a prospective epidemiological investigation.
AB  - BACKGROUND: Human leukocyte antigen (HLA)-B*5701 is strongly associated with
      developing a hypersensitivity reaction to abacavir (ABC). Limited data exist on
      HLA-B*5701 prevalence in HIV-1-infected subjects in China. We investigated HLA
      B*5701 prevalence in HIV-1-infected population including Han and non-Han ethnic
      groups. METHODS: A prospective multi-centre study was designed to determine
      status of HLA-B*5701 in HIV-1-infected adults at six sites across China. HLA
      B*5701 was tested by the method of PCR-SSP. RESULTS: From six centers, 3,000 HIV
      infected patients [2,452 (81.7%) Han, 548 (18.3%) Non-Han] were recruited with a
      mean age of 36.7 years old. The overall HLA-B*5701 prevalence was 0.86% [95%
      confidence interval (CI) 0.55-1.26%]. The prevalence of HLA-B*5701 among Han
      subjects was similar to that among non-Han subjects, which was 0.88% (95% CI 0.54
      1.34%) and 0.76% (95% CI 0.19-1.93%), respectively (p value = 0.787). There were
      no differences in prevalence of HLA-B*5701 between subjects born in Henan,
      Yunnan, Shanxi, Guangdong, Hebei, Beijing and other provinces (p = 0.999).
      CONCLUSIONS: HLA-B*5701 prevalence is very low in HIV-infected Chinese subjects,
      both in the Han and Non-Han nationalities. And there are no differences among
      different birthplaces across China.

PMID- 26300951
TI  - Socio-medical determinants of timely breastfeeding initiation in Ethiopia:
      Evidence from the 2011 nation wide Demographic and Health Survey.
AB  - BACKGROUND: Early initiation of breastfeeding is a simple and cost effective
      intervention to advance the health of mothers and newborns. The World Health
      Organization (WHO) and United Nations Children's Fund (UNICEF) recommend that
      breastfeeding should be initiated within one hour of birth. The aim of this study
      is to identify factors associated with timely initiation of breastfeeding among
      mothers in Ethiopia within one hour of birth. METHODS: This study used data from
      the 2011 Ethiopia Demographic and Health Survey. A total of 11,654 households
      were included in the analysis from 11 administrative states of Ethiopia.
      Bivariate and multivariable logistic regression models with adjusted odds ratio
      (AOR) and 95 % confidence intervals (CI) were used to quantify predictors of
      early breastfeeding initiation. RESULTS: The overall prevalence of timely
      breastfeeding initiation was 52 % (95 % CI: 51.09, 52.91). The prevalence was
      higher in urban settings (61.4 %; 95 % CI: 58.85, 63.85) than in rural areas
      (52.3 %; 95 % CI: 51.33, 53.28). The highest prevalence was found in Addis Ababa
      71.5 % (95 % CI: 64.88, 77.12) while the lowest prevalence was 41.7 % (95 % CI:
      36.62, 47.00) in Somali regional state. Multivariable logistic regression
      analysis showed that rural mothers had 39 % lower odds of timely breastfeeding
      initiation (AOR 0.61; 95 % CI: 0.50, 0.76) compared to urban mothers. Mothers who
      had secondary education or higher had 60 % higher odds of timely breastfeeding
      initiation (AOR 1.6; 95 % CI: 1.02, 2.44) than never educated mothers. Mothers
      who had caesarian deliveries had 61 % lower odds of timely breastfeeding
      initiation (AOR 0.39; 95 % CI: 0.22, 0.71) compared to vaginal deliveries.
      Working mothers were 23 % less likely to timely initiate breastfeeding (AOR 0.77;
      95 % CI: 0.69, 0.85) compared to housewives. Female infants had a 20 % higher
      chance of timely breastfeeding initiation (AOR 1.2; 95 % CI: 1.05, 1.30) compared
      to male infants. CONCLUSION: Early initiation of breastfeeding within the first
      hour after birth was not optimal  in Ethiopia. Factors such as place of
      residence, educational level, occupation, gender of the newborn and type of
      delivery should be considered in any intervention program in order to enhance
      timely breastfeeding initiation.

PMID- 26300952
TI  - The influence of infant feeding attitudes on breastfeeding duration: evidence
      from a cohort study in rural Western Australia.
AB  - BACKGROUND: Breast milk is the optimal source of nutrition for infants in the
      first six months of life. Promoting and protecting breastfeeding is reflected in
      public health policy across the globe, but breastfeeding rates in both developing
      and industrialised countries continue to demonstrate that few mothers meet these
      recommendations. In addition to sociodemographic factors such as age, education
      and income, modifiable factors such as maternal infant feeding attitudes have
      been shown to influence breastfeeding duration. The objective of this paper was
      to describe the influence of infant feeding attitudes on breastfeeding duration
      in rural Western Australia. METHODS: A cohort of 427 women and their infants were
      recruited from hospitals in rural Western Australia and followed for a period of
      12 months. Information about feeding methods was gathered in hospital and at a
      further seven follow-up contacts. Infant feeding attitude was measured using the
      Iowa Infant Feeding Attitude Scale (IIFAS), and a score of > 65 was considered
      positive towards breastfeeding. RESULTS: Mothers with an IIFAS score of > 65 were
      approximately twice as likely to be exclusively breastfeeding at six months, and
      breastfeeding at any intensity to 12 months. The median duration of exclusive
      breastfeeding for mothers with an IIFAS score of > 65 was 16 weeks (95 % CI 13.5,
      18.5) compared with 5 weeks for those with a score < 65 (95 % CI 3.2, 6.8) (p <
      0.0001). The median duration of any breastfeeding to 12 months was more than
      twice as long for mothers with an IIFAS score > 65 (48 vs. 22 weeks, p < 0.001).
      CONCLUSIONS: Women in this rural cohort who had a more positive attitude towards
      breastfeeding had a longer duration of both exclusive breastfeeding to six months
      and any breastfeeding to 12 months. Further research examining the breastfeeding
      attitudes of specific subgroups such as men, grandparents and adolescents in
      rural areas will contribute to the evidence base and help to ensure that
      breastfeeding is seen as the normal method of infant feeding.

PMID- 26300953
TI  - Optimisation approaches for concurrent transmitted light imaging during confocal
      microscopy.
AB  - BACKGROUND: The transmitted light detectors present on most modern confocal
      microscopes are an under-utilised tool for the live imaging of plant cells. As
      the light forming the image in this detector is not passed through a pinhole, out
      of-focus light is not removed. It is this extended focus that allows the
      transmitted light image to provide cellular and organismal context for
      fluorescence optical sections generated confocally. More importantly, the
      transmitted light detector provides images that have spatial and temporal
      registration with the fluorescence images, unlike images taken with a separately
      mounted camera. RESULTS: Because plants often provide difficulties for taking
      transmitted light images, with the presence of pigments and air pockets in
      leaves, this study documents several approaches to improving transmitted light
      images beginning with ensuring that the light paths through the microscope are
      correctly aligned (Kohler illumination). Pigmented samples can be imaged in real
      colour using sequential scanning with red, green and blue lasers. The resulting
      transmitted light images can be optimised and merged in ImageJ to generate colour
      images that maintain registration with concurrent fluorescence images. For faster
      imaging of pigmented samples, transmitted light images can be formed with non
      absorbed wavelengths. Transmitted light images of Arabidopsis leaves expressing
      GFP can be improved by concurrent illumination with green and blue light. If the
      blue light used for YFP excitation is blocked from the transmitted light detector
      with a cheap, coloured glass filters, the non-absorbed green light will form an
      improved transmitted light image. Changes in sample colour can be quantified by
      transmitted light imaging. This has been documented in red onion epidermal cells
      where changes in vacuolar pH triggered by the weak base methylamine result in
      measurable colour changes in the vacuolar anthocyanin. CONCLUSIONS: Many plant
      cells contain visible levels of pigment. The transmitted light detector provides
      a useful tool for documenting and measuring changes in these pigments while
      maintaining registration with confocal imaging.

PMID- 26300954
TI  - The new Lyon ARTbrace versus the historical Lyon brace: a prospective case series
      of 148 consecutive scoliosis with short time results after 1 year compared with a
      historical retrospective case series of 100 consecutive scoliosis; SOSORT award
      2015 winner.

PMID- 26300955
TI  - Surgical results with the use of Silicated Calcium Phosphate (SiCaP) as bone
      graft substitute in Posterior Spinal Fusion (PSF) for Adolescent Idiopathic
      Scoliosis (AIS).
AB  - BACKGROUND: The gold standard iliac crest bone graft (ICBG) used to achieve
      arthrodesis in spinal fusions is not without complications (donor-site morbidity,
      iliac wing fractures etc....). Our objectives were to evaluate the role of
      silicated calcium phosphate (SiCaP), an osteoconductive synthetic bone graft
      substitute in conjunction with locally harvested autologous bone in achieving
      arthrodesis following posterior spinal fusion (PSF) for adolescent idiopathic
      scoliosis (AIS) and report clinic-radiological results / adverse events with its
      use in a prospective single surgeon case series (Level of evidence [LoE] IV)
      treated by low implant density index (IDI) constructs (i.e., IDI <=1.5). METHODS:
      Thirty-five patients (8? & 2727?) who underwent PSF and followed-up for a minimum
      of 2 years formed the study cohort. The mean age at surgery was 15 years (range:
      11-21y) and pre-op Cobb angle was 60 degrees  (range: 40 degrees -90 degrees ).
      SiCaP mixed with locally harvested bone during exposure and instrumentation was
      laid over instrumented segments. The average SiCaP used per patient was 32mls
      (range: 10-60mls). Radiographs were assessed for fusion at serial six monthly
      follow-ups. All clinical adverse events and complications were recorded. RESULTS:
      The mean follow-up was 2.94 years (range: 2-4y). The post-op Cobb angle improved
      to 23 degrees  (range: 2 degrees - 55 degrees ) and the mean in-patient stay was
      7.72 days (range: 5-13d). The mean number of instrumented segments was 9.4
      (range: 4-13) and implant density index (IDI) averaged 1.23 (range: 1.15-1.5).
      Radiographic new bone formation was seen within 3 months in all cases. All
      patients (except two) were highly satisfied at minimum follow-up of 8 years.
      There were two complications warranting revision surgery (deep infection, and
      implant failure without any evidence of pseudarthrosis). There were no SiCaP
      specific adverse events in any of the 35 patients. CONCLUSION: SiCaP facilitated
      early bony consolidation in operated cohort of AIS patients treated by PSF. There
      were no inflammatory reaction or other adverse effects associated with its use.
      SiCaP is a safe alternative to autologous iliac crest bone graft with reduced
      complications, morbidity, faster recovery and similar infection/fusion rates
      reported in the literature.

PMID- 26300957
TI  - Identification of commercial Ganoderma (Lingzhi) species by ITS2 sequences.
AB  - BACKGROUND: DNA barcoding can be used to authenticate Ganoderma species for safe
      use. This study aims to identify commercial products containing Ganoderma using
      DNA barcoding. METHODS: We used 63 internal transcribed spacer (ITS) 2 sequences
      of Ganoderma species from 33 newly-sequenced wild samples, crude drugs, mycelia,
      spores, and authentic extracts and spore oils collected from various locations
      and markets, as well as 30 sequences from GenBank. Sequences were assembled and
      aligned using CodonCode Aligner V3.71. Intra- and inter-specific distances were
      estimated by MEGA 6.0, and phylogeny reconstruction was based on the K2P model.
      SNP(s) and RNA secondary structure of ITS2 were analyzed and compared among
      closely related Ganoderma species. RESULTS: G. lucidum cultivated in China was
      different from those cultivated in Europe. "Chizhi" (G. lucidum) and "Zizhi" (G.
      sinense) were clustered into two clades that were separated from the other
      Ganoderma species. The fruiting bodies and commercial products of G. lucidum and
      G. sinense were successfully distinguished from those of other Ganoderma species
      by comparing the ITS2 sequences and RNA secondary structures. CONCLUSION: The DNA
      barcoding method is applicable to the authentication of commercial products
      containing Ganoderma species.

PMID- 26300958
TI  - Crude triterpenoid saponins from Ilex latifolia (Da Ye Dong Qing) ameliorate
      lipid accumulation by inhibiting SREBP expression via activation of AMPK in a non
      alcoholic fatty liver disease model.
AB  - BACKGROUND: Ilex latifolia Thunb. (Da Ye Dong Qing) is used for weight loss and
      for its antidiabetic effects. This study aims to investigate the beneficial
      effects and potential mechanisms of action of crude triterpenoid saponins (CTS)
      from I. latifolia in a mouse model of high-fat diet (HFD)-induced non-alcoholic
      fatty liver disease (NAFLD). METHODS: Male C57BL/6 mice (n = 50), were
      arbitrarily divided into five groups (n = 10 in each group): a control group, HFD
      group, simvastatin group (10 mg/kg/day), and two CTS treatment groups (100 and
      200 mg/kg/day). All mice except those in the control group were fed an HFD for 4
      weeks. Animals in the treatment groups were orally administered simvastatin or
      CTS for 8 weeks. Oral glucose tolerance tests and insulin tolerance tests were
      performed. At the end of treatment, plasma lipid levels, and oxidative parameters
      in the liver were measured using commercial test kits. Western blotting was used
      to evaluate whether CTS induced AMP-activated protein kinase (AMPK) and acetyl
      CoA carboxylase activation, and the expression of transcription factors and their
      target genes was evaluated in a quantitative PCR assay. RESULTS: Compared with
      the HFD group, the CTS (200 mg/kg/day) treatment group showed significantly
      decreased plasma lipid parameters (P < 0.001, P = 0.018, and P = 0.005 for
      triglycerides, total cholesterol and low-density lipoprotein cholesterol,
      respectively), and improved insulin resistance (P = 0.006). CTS (100 and 200
      mg/kg/day) supplementation also reduced hepatic lipids and protected the liver
      from oxidative stress by attenuating malondialdehyde content (P < 0.001 and P <
      0.001, respectively) and restoring aspartate aminotransferase levels (P < 0.001
      and P < 0.001, respectively). Moreover, CTS (200 mg/kg/day) reduced lipid
      accumulation by enhancing AMPK phosphorylation and inhibiting expression of
      sterol regulatory element-binding proteins (SREBPs) and their target genes SREBP
      1c, SREBP-2, fatty acid synthase, and stearoyl-CoA desaturase (P = 0.013, P =
      0.007, P = 0.011, and P = 0.014, respectively). CONCLUSION: CTS from I. latifolia
      improved insulin resistance and liver injury in HFD-fed mice, and attenuated
      NAFLD via the activation of AMPK and inhibition of the gene expression of SREBPs
      and some of their target molecules.

PMID- 26300959
TI  - Impact of service provision platforms on maternal and newborn health in conflict
      areas and their acceptability in Pakistan: a systematic review.
AB  - Various models and strategies have been implemented over the years in different
      parts of the world to improve maternal and newborn health (MNH) in conflict
      affected areas. These strategies are based on specific needs and acceptability of
      local communities. This paper has undertaken a systematic review of global and
      local (Pakistan) information from conflict areas on platforms of health service
      provision in the last 10 years and information on acceptability from local
      stakeholders on effective models of service delivery; and drafted key
      recommendations for improving coverage of health services in conflict affected
      areas. The literature search revealed ten studies that described MNH service
      delivery platforms. The results from the systematic review showed that with
      utilisation of community outreach services, the greatest impacts were observed in
      skilled birth attendance and antenatal consultation rates. Facility level
      services, on the other hand, showed that labour room services for an internally
      displaced population (IDP) improved antenatal care coverage, contraceptive
      prevalence rate and maternal mortality. Consultative meetings and discussions
      conducted in Quetta and Peshawar (capitals of conflict affected provinces) with
      relevant stakeholders revealed that no systematic models of MNH service delivery,
      especially tailored for conflict areas, are available. During conflict, even
      previously available services and infrastructure suffered due to various barriers
      specific to times of conflict and unrest. A number of barriers that hinder MNH
      services were discussed. Suggestions for improving MNH services in conflict areas
      were also laid down by participants. The review identified some important steps
      that can be undertaken to mitigate the effects of conflict on MNH services, which
      include: improve provision and access to infrastructure and equipment;
      development and training of healthcare providers; and advocacy at different
      levels for free access to healthcare services and for the introduction of the
      programme model in existing healthcare system. The obligation is enormous,
      however, for a sustainable programme, it is important to work closely with both
      the IDP and host community, and collaborating with the government and non
      government organisations. 

PMID- 26300960
TI  - A pilot study of a portable hand washing station for recently displaced refugees
      during an acute emergency in Benishangul-Gumuz Regional State, Ethiopia.
AB  - BACKGROUND: Diarrheal disease is a common cause of morbidity and mortality.
      Displaced populations are especially vulnerable due to overcrowded camps and
      limited access to water and sanitation facilities, increasing the risk for
      outbreaks. Hand washing with soap is effective against disease transmission, and
      studies suggest access to a convenient hand washing station may be the key to
      increasing hand washing behavior. This pilot study evaluated the acceptability,
      durability and use of a novel hand washing bag (HWB) at the household level among
      Sudanese refugees immediately following an acute emergency. METHODS: We
      distributed one HWB to every household (n = 874) in Adamazin Transit Center in
      western Ethiopia. The evaluation consisted of baseline and endline surveys, three
      monthly monitoring visits and focus group discussions (FGDs) over a six month
      period. FGD data were analyzed using the Risk, Attitudes, Norms, Abilities, and
      Self-Regulatory model. Survey and monitoring data were analyzed using SPSS. Note:
      Residents were resettled to Bambasi Refugee Camp during the study period where
      the endline survey was conducted. RESULTS: Baseline data suggested water quantity
      and availability of soap were below SPHERE standards, however participants
      responded positively to the HWB. At the end of the monitoring period, 73.9 % of
      the same households retained their original HWBs and 66.7 % of bags had water at
      the time of the visit. The mean lifespan of the HWB during the monitoring period
      was 2.73 months. From a new sample of households selected for the endline
      evaluation, 93.0 % had an original HWB, but only 39.4 % had water in the bag.
      Endline FGD participants felt the HWB was useful, but reported insufficient soap
      and hygiene messaging. CONCLUSION: The HWB performed well during the early phases
      of the emergency, however longer term results in this setting are unclear. The
      low levels of reported use measured by proxy indicators at six months indicated
      decreasing acceptability over time or a reflection of potential differences
      between the two sites. It is also unknown whether the HWB influenced hand washing
      behavior. Study findings were shared with the manufacturer in an effort to
      improve the bag's acceptability, utility, and durability.

PMID- 26300961
TI  - Synthesis and biological evaluation of new nanosized aromatic polyamides
      containing amido- and sulfonamidopyrimidines pendant structures.
AB  - BACKGROUND: Antibiotics are biocides or products that inhibit the growth of
      microorganisms in the living cells and there are extensive works directed to
      develop efficient antimicrobial agents. The sulfonamide-containing polymers have
      great potential to resist gram-positive or gram-negative bacterial and fungal
      attacks. As a therapeutic agent, the sulfonamides have been reported as antitumor
      and antimicrobial agents against bacteria, being more potent against gram
      positive rather than gram negative strains. Design of new classes of inhibitors
      bearing fluorescent tails, as therapeutic and imaging agents, is currently an
      active area of research. Here, we describe the synthesis of a new family of
      polyamides based on chlorophenyl-3,5-diaminobenzamides, methyl substituted
      pyrimidinoamido-3,5-diamino- benzamides and methyl substituted
      pyrimidinosulfonamido-3,5-diaminobenzamides and evaluation of their thermal,
      optical and antimicrobial properties. RESULTS: We report the synthesis of a new
      series of nanosized polyamides containing bioactive pendent structures. The
      spherical nanosized polymer particles are soluble in many organic solvents and
      exhibited emissions ranging from blue to orange wavelength depending on the
      nature of the signaling unit. Pyrimidine- and p-chloroaromatic containing
      polymers exhibited higher bioactivity than that contain the sulfonamide group.
      The amidopyrimidine polymers exhibited remarkable antifungal and antibacterial
      activity and thus, these types of polymers are promising candidates for
      biomedical applications. CONCLUSIONS: The SEM analysis indicated that most of the
      polyamides were organized as well defined nano sized spheres, but in certain
      derivatives small amount of aggregated nanospheres were also observed. Thermal
      analyses were studied up to 700  degrees C and results showed comparable thermal
      behavior. The optical results revealed that polymeric series (A) exhibited orange
      emission, series (B) showed green emission while series (C) exhibited yellow and
      blue emissions. Benzene/pyridine structure interchange resulted in red shifted
      peaks attributed to the localized lone pair of electrons on a nitrogen atom which
      offer a greater electron affinity and better electron-transporting properties.
      The amido- and sulfonamide pyrimidine containing polymers exhibited the most
      potent antimicrobial activity. Relative to the reference Gentamicin, the polymer
      54 exhibited comparable antibacterial activity against gram negative bacteria.
      Analogues 52 and 57 exhibited remarkable antibacterial activities compared to the
      references used. Thus, these polyamides are likely to be promising broad spectrum
      antibacterial agents and deserve further investigation at the molecular
      level.Graphical abstract:The synthesis and characterization of a new series of
      nanosized polyamides containing chloroaromatic (A), pyrimidinoamido- (B) and
      pyrimidosulfonamido- (C) pendent structures as promising candidates for
      biomedical applications is described.

PMID- 26300962
TI  - Selection of depression measures for use among Vietnamese populations in primary
      care settings: a scoping review.
AB  - Depression is an important and growing contributor to the burden of disease
      around the world and evidence suggests the experience of depression varies cross
      culturally. Efforts to improve the integration of services for depression in
      primary care are increasing globally, meaning that culturally valid measures that
      are acceptable for use in primary care settings are needed. We conducted a
      scoping review of 27 studies that validated or used 10 measures of depression in
      Vietnamese populations. We reviewed the validity of the instruments as reported
      in the studies and qualitatively assessed cultural validity and acceptability for
      use in primary care. We found much variation in the methods used to validate the
      measures, with an emphasis on criterion validity and reliability. Enhanced
      evaluation of content and construct validity is needed to ensure validity within
      diverse cultural contexts such as Vietnam. For effective use in primary care,
      measures must be further evaluated for their brevity and ease of use. To identify
      appropriate measures for use in primary care in diverse populations, assessment
      must balance standard validity testing with enhanced testing for appropriateness
      in terms of culture, language, and gender and for acceptability for use in
      primary care. 

PMID- 26300963
TI  - Doing mental health care integration: a qualitative study of a new work role.
AB  - BACKGROUND: Mental health care in Australia is fragmented and inaccessible for
      people experiencing severe and complex mental ill-health. Partners in Recovery is
      a Federal Government funded scheme that was designed to improve coordination of
      care and needs for this group. Support Facilitators are the core service delivery
      component of this scheme and have been employed to work with clients to
      coordinate their care needs and, through doing so, bring the system closer
      together. OBJECTIVE: To understand how Partners in Recovery Support Facilitators
      establish themselves as a new role in the mental health system, their experiences
      of the role, the challenges that they face and what has enabled their work.
      METHODS: In-depth qualitative interviews were carried out with 15 Support
      Facilitators and team leaders working in Partners in Recovery in two regions in
      Western Sydney (representing approximately 35 % of those working in these roles
      in the regions). Analysis of the interview data focused on the work that the
      Support Facilitators do, how they conceptualise their role and enablers and
      barriers to their work. RESULTS: The support facilitator role is dominated by
      efforts to seek out, establish and maintain connections of use in addressing
      their clients' needs. In doing this Support Facilitators use existing interagency
      forums and develop their own ad hoc groupings through which they can share
      knowledge and help each other. Support Facilitators also use these groups to
      educate the sector about Partners in Recovery, its utility and their own role.
      The diversity of support facilitator backgrounds are seen as both and asset and a
      barrier and they describe a process of striving to establish an internally
      collective identity as well as external role clarity and acceptance. At this
      early stage of PIR establishment, poor communication was identified as the key
      barrier to Support Facilitators' work. CONCLUSIONS: We find that the Support
      Facilitators are building the role from within and using trial and error to
      develop their practice in coordination. We argue that a strong organisational
      hierarchy is necessary for support facilitation to be effective and to allow the
      role to develop effectively. We find that their progress is limited by overall
      program instability caused by changing government policy priorities.

PMID- 26300964
TI  - Delayed identification and diagnosis of Huntington's disease due to psychiatric
      symptoms.
AB  - Huntington's disease (HD) is a progressive neurodegenerative illness that affects
      2-9/100.000 of the general population. The usual onset is at around age 35-40
      years, but there were cases with onset above 55 years. The disease manifests
      clinically with many neurological and psychiatric symptoms, leading in advanced
      phases to dementia, but cognitive symptoms are frequently present much earlier in
      the disease course. HD is caused by an expanded polyglutamine stretch in the N
      terminal part of a 350 kDa protein called huntingtin (HTT). This stretch is
      encoded by a trinucleotide CAG repetition in exon 1 of HTT. An expansion of
      greater than 36 repeats results in HD. The number of repeats is inversely
      correlated with the age of onset of motor symptoms, and disease onset during
      childhood or adolescence is associated with more than 60 CAG repeats. Mood
      disturbances may be one of the earliest symptoms of HD and may precede the onset
      of the motor pheno-type for almost 10 years. Neuropsychiatric symptoms may delay
      the appropriate diagnosis of HD and have major implications for disease
      management, prognosis and quality of life for patients and families. This case
      study is about a 58 years old female patient with late identification of
      Huntington's disease after two admissions to psychiatric inpatient units, for the
      treatment of behavioral disturbances. 

PMID- 26300965
TI  - Reasons and pathways of first-time consultations at child and adolescent mental
      health services in Italy: an observational study.
AB  - BACKGROUND: An increasing number of young people have made contact with the Child
      and Adolescent Mental Health Services (CAMHS). However, only a small proportion
      of the population with emotional problems, actually seek specialized care.
      Research concerning the help-seeking process and pathways to care of a clinical
      sample could help to develop effective health policies to facilitate access to
      specialized care. AIM: To analyze the access pattern for CAMHS, reasons of
      contact and care pathways of a consecutive sample of first-time patients. Our aim
      was to analyze the association between source of referral, socio-demographic and
      clinical variables. METHODS: Standardized assessment instruments and information
      concerning access patterns and care pathways were collected from 399 patients at
      first-time contact with CAMHS in a Northern Italian Region. RESULTS: Most
      patients were referred to CAMHS by school teachers (36 %) or health professionals
      (32 %), while only 17 % of the parents sought help by themselves. School issues
      (50 %) and emotional problems (17 %) were the most frequent reasons for contact.
      The proportion of first-time contacts with no diagnosis of mental disorder at
      their first consultation did not differ by source of referral. Parents of
      children who did not receive a clinical diagnosis of mental disorders described
      them as "psychosocially impaired" and their condition as "clinically severe"
      likewise parents of patients who received a psychiatric diagnosis. Patients with
      externalizing problems were more frequently referred by the parents themselves,
      while youth with internalizing problems were more often referred through health
      professionals. Families with non-traditional structures (adoptive, foster care,
      mono-parental) were more likely to consult CAMHS directly, while immigrant youth
      were more often referred by teachers. CONCLUSION: Socio-demographic and clinical
      characteristics can affect pathways to care. To improve early access to care for
      children and adolescents with ongoing mental disorders, a plan for proper action
      addressed to teachers and health professionals may well be important. This would
      improve their ability to recognize emotional and behavioral problems and use
      proper referral pathways, while informative intervention addressed to non-Italian
      families should inform them about the functioning and the mission of CAMHS.

PMID- 26300966
TI  - Adolescents' reactions to participating in ethically sensitive research: a
      prospective self-report study.
AB  - BACKGROUND: Conducting psychological research with adolescents is imperative for
      better understanding, prevention and treatment of mental illness. However there
      is concern that research addressing topics such as mental illness, substance use
      and suicidality has potential to distress participants, particularly youth.
      METHOD: We administered a questionnaire to 1973 adolescents (13-18 years) at two
      time points, one year apart. Participants responded to items regarding
      nonsuicidal self-injury, psychological distress, history of physical and/or
      sexual abuse, adverse life events, alcohol use, suicidal behaviour, self
      efficacy, and coping skills as well as two open-ended questions regarding whether
      they enjoyed participating in the research and whether participation worried or
      upset them. RESULTS: Most youth (74 %) enjoyed participation and cited altruistic
      reasons and a greater self-awareness as reasons. Those reporting being upset by
      the questionnaire (15 %) reported poorer psychological functioning than their
      peers. Youth who were upset by their participation at baseline, but who reported
      enjoying the questionnaire at follow-up reported improved psychosocial
      functioning over time, while the reverse was true for those who initially enjoyed
      participation but later reported the questionnaire upset them. CONCLUSIONS:
      Results suggest researchers acknowledge benefits for young people who participate
      in research, but also be mindful of the potential for distress among the most at
      risk youth.

PMID- 26300967
TI  - Parents' perception of child and adolescent mental health problems and their
      choice of treatment option in southwest Ethiopia.
AB  - BACKGROUND: Parents' perception and awareness about psychiatric illness in
      children and adolescents is an important determinant of early detection and
      treatment seeking for the condition. However, there has been limited information
      about the perception and awareness of parents about these issues as well as their
      preferred treatment options in Ethiopia. This study is, therefore, aimed at
      assessing the perception of parents about psychiatric illness in children and
      adolescents and their preferred treatment options in Jimma, Ethiopia. METHOD: A
      cross-sectional study was conducted among 532 parents in Jimma City, Ethiopia
      from April to May 2013. Parents from the city were invited to participate in this
      study to assess their knowledge on causes, and manifestations of psychiatric
      illness in children and adolescents as well as their preferred treatment options
      if their children exhibited signs and symptoms of mental illness. RESULTS: Nearly
      three quarters of the parents identified genetic factors while approximately 20 %
      of them mentioned neuro-chemical disturbance as possible causes of their
      children's mental health problems. On the other hand, magic, curse, and sin were
      mentioned as causes of mental health problems by 93.2, 81.8 and 73.9 % of the
      parents, respectively. Externalizing behavioral symptoms like "stealing from
      home, school or elsewhere" and internalizing symptoms like "being nervous in new
      situations and easily loses confidence" were perceived by 60.9 and 38.2 % of the
      parents, respectively. The majority (92.7 %) of parents agreed that they would
      seek treatment either from religious or spiritual healers if their children
      developed mental illness. CONCLUSIONS: The low level of awareness about
      internalizing symptoms, the widespread traditional explanatory models as well as
      preference for traditional treatment options might present significant challenges
      to utilization of child and adolescent mental health services in this population.
      Public health intervention programs targeting parental attitude regarding the
      causes and treatment for child and adolescent mental health problems need to be
      designed and evaluated for their effectiveness in low-income settings.
      Additionally, including religious and spiritual leaders in the process of
      educating members of their respective churches and mosques should also be
      explored.

PMID- 26300968
TI  - Do girls with depressive symptoms exhibit more physical aggression than boys? A
      cross sectional study in a national adolescent sample.
AB  - BACKGROUND: The relationship between depression and aggressive behaviors in
      adolescents has previously been reported in clinical and epidemiological studies.
      However, there is conflicting evidence concerning the effect of gender on this
      relationship. This study tested whether the link between depressive symptoms and
      physical aggression differed between boys and girls in a large community-based
      sample of adolescents. METHODS: A cross-sectional sample of adolescents aged 15
      19 (N = 6,677) was studied within the 2007 ESPAD national survey. Depressive
      symptoms were assessed using the Adolescent Depression Rating Scale. We
      distinguished adolescents with subthreshold levels of depressive symptoms and
      adolescents with clinically significant levels of depressive symptoms. Physical
      aggressive behaviors in the last year were reported using items from the
      Antisocial Behavior Scale. RESULTS: After adjusting for confounding variables,
      the odds-ratio between depressive symptoms and physical aggressive behaviors was
      around 1.4. This relationship was stronger for girls than for boys in presence of
      clinically significant levels of depressive symptoms, but did not differ between
      the genders in the case of subthreshold levels of depressive symptoms.
      CONCLUSIONS: Girls with severe depressive symptoms were more likely to present
      physical aggressive behaviors than boys. Future studies will be needed to explore
      the role of irritability in these differences.

PMID- 26300956
TI  - WSES guidelines for management of Clostridium difficile infection in surgical
      patients.
AB  - In the last two decades there have been dramatic changes in the epidemiology of
      Clostridium difficile infection (CDI), with increases in incidence and severity
      of disease in many countries worldwide. The incidence of CDI has also increased
      in surgical patients. Optimization of management of C difficile, has therefore
      become increasingly urgent. An international multidisciplinary panel of experts
      prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for
      management of CDI in surgical patients. 

PMID- 26300969
TI  - The long-term effects of being bullied or a bully in adolescence on externalizing
      and internalizing mental health problems in adulthood.
AB  - BACKGROUND: The aim is to examine associations between bullying involvement in
      adolescence and mental health problems in adulthood. METHODS: Information on
      bullying-involvement (being bullied, bully-victim, aggressive toward others) and
      non-involved was collected from 2464 adolescents in Mid-Norway at mean age 13.7
      and again at mean age 14.9. Information about mental health problems and
      psychosocial functioning was collected about 12 years later at mean age 27.2 (n =
      1266). RESULTS: All groups involved in bullying in young adolescence had adverse
      mental health outcomes in adulthood compared to non-involved. Those being bullied
      were affected especially regarding increased total sum of depressive symptoms and
      high levels of total, internalizing and critical symptoms, increased risk of
      having received help for mental health problems, and reduced functioning because
      of a psychiatric problem in adulthood. While those being aggressive toward others
      showed high levels of total and internalizing symptoms. Both those being bullied
      and bully-victims showed an increased risk of high levels of critical symptoms.
      Lastly, all groups involved in bullying on adolescence had increased risk of
      psychiatric hospitalization because of mental health problems. CONCLUSION:
      Involvement in bullying in adolescence is associated with later mental health
      problems, possibly hindering development into independent adulthood.

PMID- 26300970
TI  - Chemical and structural changes associated with Cu-catalyzed alkaline-oxidative
      delignification of hybrid poplar.
AB  - BACKGROUND: Alkaline hydrogen peroxide pretreatment catalyzed by Cu(II) 2,2'
      bipyridine complexes has previously been determined to substantially improve the
      enzymatic hydrolysis of woody plants including hybrid poplar as a consequence of
      moderate delignification. In the present work, cell wall morphological and lignin
      structural changes were characterized for this pretreatment approach to gain
      insights into pretreatment outcomes and, specifically, to identify the extent and
      nature of lignin modification. RESULTS: Through TEM imaging, this catalytic
      oxidation process was shown to disrupt cell wall layers in hybrid poplar. Cu
      containing nanoparticles, primarily in the Cu(I) oxidation state, co-localized
      with the disrupted regions, providing indirect evidence of catalytic activity
      whereby soluble Cu(II) complexes are reduced and precipitated during
      pretreatment. The concentration of alkali-soluble polymeric and oligomeric lignin
      was substantially higher for the Cu-catalyzed oxidative pretreatment. This alkali
      soluble lignin content increased with time during the catalytic oxidation
      process, although the molecular weight distributions were unaltered. Yields of
      aromatic monomers (including phenolic acids and aldehydes) were found to be less
      than 0.2 % (wt/wt) on lignin. Oxidation of the benzylic alcohol in the lignin
      side-chain was evident in NMR spectra of the solubilized lignin, whereas minimal
      changes were observed for the pretreatment-insoluble lignin. CONCLUSIONS: These
      results provide indirect evidence for catalytic activity within the cell wall.
      The low yields of lignin-derived aromatic monomers, together with the detailed
      characterization of the pretreatment-soluble and pretreatment-insoluble lignins,
      indicate that the majority of both lignin pools remained relatively unmodified.
      As such, the lignins resulting from this process retain features closely
      resembling native lignins and may, therefore, be amenable to subsequent
      valorization.

PMID- 26300972
TI  - Implementation of a novel living-donor kidney transplant preoperative checklist
      within the electronic medical record: a pilot study.
AB  - BACKGROUND: Checklist utilization in surgery has contributed to improved patient
      safety and reduced numbers of preventable complications. A living-donor kidney
      transplant (LDKT) preoperative checklist embedded within electronic medical
      record (EMR) was developed to enhance patient safety and prevent "never" events
      including: unexpected donor-recipient blood (ABO) incompatibility, positive (XM)
      cross match, infectious disease transmission, or procurement of an anatomically
      inappropriate allograft. Review of the initial 2 years of checklist utilization
      was performed. FINDINGS: This safety instrument operates by facilitating critical
      review and referencing of source documentation to confirm ABO, XM, infectious
      risk, and organ anatomy compatibility. It was met with high compliance rates and
      no "never events" have occurred following its inception. The checklist is readily
      available in the EMR and is accessible by all members of the LDKT recipient
      healthcare team. CONCLUSIONS: Checklist utilization was associated with zero LDKT
      "never event" occurrences. Surgeons felt the checklist was easy to use.

PMID- 26300971
TI  - Involvement of the adaptor protein 3 complex in lignocellulase secretion in
      Neurospora crassa revealed by comparative genomic screening.
AB  - BACKGROUND: Lignocellulase hypersecretion has been achieved in industrial fungal
      workhorses such as Trichoderma reesei, but the underlying mechanism associated
      with this process is not well understood. Although previous comparative genomic
      studies have revealed that the mutagenic T. reesei strain RUT-C30 harbors
      hundreds of mutations compared with its parental strain QM6a, how these mutations
      actually contribute to the hypersecretion phenotype remains to be elucidated.
      RESULTS: In this study, we systematically screened gene knockout (KO) mutants in
      the cellulolytic fungus Neurospora crassa, which contains orthologs of
      potentially defective T. reesei RUT-C30 mutated genes. Of the 86 deletion mutants
      screened in N. crassa, 12 exhibited lignocellulase production more than 25%
      higher than in the wild-type (WT) strain and 4 showed nearly 25% lower secretion.
      We observed that the deletion of Ncap3m (NCU03998), which encodes the MU subunit
      of the adaptor protein 3 (AP-3) complex in N. crassa, led to the most significant
      increase in lignocellulase secretion under both Avicel and xylan culture
      conditions. Moreover, strains lacking the beta subunit of the AP-3 complex,
      encoded by Ncap3b (NCU06569), had a similar phenotype to DeltaNcap3m, suggesting
      that the AP-3 complex is involved in lignocellulase secretion in N. crassa. We
      also found that the transcriptional abundance of major lignocellulase genes in
      DeltaNcap3m was maintained at a relatively higher level during the late stage of
      fermentation compared with the WT, which might add to the hypersecretion
      phenotype. Finally, we found that importation of the T. reesei ap3m ortholog
      Trap3m into DeltaNcap3m can genetically restore secretion of lignocellulases to
      normal levels, which suggests that the effect of the AP-3 complex on
      lignocellulase secretion is conserved in cellulolytic ascomycetes. CONCLUSIONS:
      Using the model cellulolytic fungus N. crassa, we explored potential
      hypersecretion-related mutations in T. reesei strain RUT-C30. Through systematic
      genetic screening of 86 corresponding orthologous KO mutants in N. crassa, we
      identified several genes, particularly those encoding the AP-3 complex that
      contribute to lignocellulase secretion. These findings will be useful for strain
      improvement in future lignocellulase and biomass-based chemical production.

PMID- 26300974
TI  - Chromosome number and ploidy level of balm (Melissa officinalis).
AB  - BACKGROUND: Lemon balm (Melissa officinalis L.) is of increasing importance
      resulting in rising growth area. Improved knowledge on the genome structure,
      number of chromosomes in connection with the taxonomical structure of balm is
      indispensable for improved new varieties. RESULTS: A collection of 40 balm
      accessions (M. officinalis) was characterized by flow cytometry and FISH (18/25S
      and 5S rDNA) to determine the chromosome number and ploidy level. Three different
      types were found: diploid genotypes with 2n = 2* = 32 chromosomes; tetraploid 2n
      = 4* = 64 chromosomes and triploid 2n = 3* = 48 chromosomes. A haploid base
      number of * = 16 chromosomes is likely. First time described triploid accessions
      are sterile but cytologically and morphologically stable for many years.
      Triploids express better winter hardiness and regeneration after harvesting cuts
      as well as bigger leaves and internodes. CONCLUSIONS: A basic chromosome number
      of x = 16 is reported for the first time for the species M. officinalis.

PMID- 26300973
TI  - Cytoglobin expression in the hepatic stellate cell line HSC-T6 is regulated by
      extracellular matrix proteins dependent on FAK-signalling.
AB  - BACKGROUND: Fibrosis is a physiological response to cellular injury in the liver
      and is mediated by the activation of hepatic stellate cells resulting in the
      replacement of hepatocytes with extracellular matrix comprised principally of
      collagen 1 to form a hepatic scar. Although the novel hexaco-ordinated globin
      cytoglobin was identified in activated hepatic stellate cells more than 10 years
      ago, its role in stellate cell biology and liver fibrosis remains enigmatic.
      RESULTS: In the current study, we investigated the role of different
      extracellular matrix proteins in stellate cell proliferation, activation (alpha
      smooth muscle actin expression and retinoic acid uptake) and cytoglobin
      expression. Our results demonstrate that cytoglobin expression is correlated with
      a more quiescent phenotype of stellate cells in culture and that cytoglobin is
      regulated by the extracellular matrix through integrin signalling dependent on
      activation of focal adhesion kinase. CONCLUSIONS: Although further studies are
      required, we provide evidence that cytoglobin is a negative regulator of stellate
      cell activation and therefore may represent a novel target for anti-fibrotic
      treatments in the future.

PMID- 26300975
TI  - Disomy 21 in spermatozoa and the paternal origin of trisomy 21 Down syndrome.
AB  - BACKGROUND: Trisomy 21 Down syndrome is the most common genetic cause for
      congenital malformations and intellectual disability. It is well known that in
      the outstanding majority of cases the extra chromosome 21 originates from the
      mother but only in less than 10 % from the father. The mechanism underlying this
      striking difference in parental origin of Trisomy 21 Down syndrome is still
      unknown. However, it seems likely that the main reason is a much higher
      stringency in the elimination of any trisomy 21 cells during fetal testicular
      than ovarian development. We have here focussed attention on the paternal gametic
      output, i.e. the incidence of disomy 21 in spermatozoa. RESULTS: We have used
      fluorescence in situ hybridisation (FISH) to determine the copy number of
      chromosome 21 in spermatozoa from 11 men with normal spermiograms. Due to the
      well-known risk of false positive and false negative signals using a single FISH
      probe, we have applied two chromosome 21q probes, and we have added a chromosome
      18-specific probe to allow differentiation between disomy 21 and diploidy.
      Analysing a total number of 2000 spermatozoa per case, we documented an average
      incidence of disomy 21 at 0.13 %, with a range of 0.00-0.25 % and a SD of 0.08.
      There was no indication of diploidy in this cohort of 22,000 sperm. CONCLUSION:
      Numerous previous studies on the incidence of disomy 21 in sperm have been
      published, using FISH. As far as we are aware, none of these have applied more
      than a single chromosome 21-specific probe. Accepting our mean of 0.13 % of
      disomy 21, and providing there is no selective fertilisation capability of disomy
      21 sperm in relation to the normal, we conclude that around 1 in 800 conceptions
      is expected to be trisomic for chromosome 21 of paternal origin. Bearing in mind
      that the maternal origin likely is at least 10 times more common, we tentatively
      propose that around 1 in 80 oocytes in the maternal ovarian reserve may be disomy
      21. One reason for this discrepancy may be a more stringent selection against
      aberrant chromosome numbers during spermatogenesis than oogenesis. Further work
      is required to determine the relevant stages of spermatogenesis at which such a
      selection may take place.

PMID- 26300976
TI  - Double inv(3)(q21q26.2) in acute myeloid leukemia is resulted from an acquired
      copy neutral loss of heterozygosity of chromosome 3q and associated with disease
      progression.
AB  - BACKGROUND: Acute myeloid leukemia (AML) with inv(3)(q21q26.2)/t(3;3)(q21;q26.2)
      is a distinct clinicopathologic entity with a poor prognosis. However, double
      inv(3)(q21q26.2) is extremely rare in AML. We report here 3 cases analyzed by
      oligonucleotide microarray comparative genomic hybridization (aCGH) and single
      nucleotide polymorphism (SNP). Clinicopathologic, cytogenetic and molecular
      findings were correlated with clinical outcome to better understand the entity.
      RESULTS: The study group included one man and two women at 56-74 years of age.
      The AML arose from myelodysplastic syndrome in one patient and from chronic
      myelomonocytic leukemia in another patient. Monosomy 7 was found as additional
      cytogenetic finding in one patient. One patient had a single inv(3) in the
      initial clone and acquired double inv(3) as part of clonal evolution. EVI1
      (MECOM) rearrangement was confirmed using metaphase/interphase fluorescence in
      situ hybridization (FISH). Microarray (aCGH + SNP) data analysis revealed that
      the double inv(3) was a result of acquiring copy neutral loss of heterozygosity
      of chromosome 3q: arr[hg19] 3q13.21q29(10,344,387-197,802,470)x2 hmz, spanning ~
      94.3 Mb in size. Mutational profiling showed a PTPN11 mutation at a low level
      (~10 %) in one patient and wild type FLT3 and RAS in all patients. No patients
      achieved cytogenetic remission and all died with an overall survival (OS) of 23,
      12 and 5 months, respectively. CONCLUSIONS: Double inv(3) is a result of acquired
      copy neutral loss of heterozygosity, a somatic repair event occurring as a part
      of mitotic recombination of the partial chromosome 3q. The double inv(3) in AML
      patients is highly associated with a rapid disease progression.

PMID- 26300977
TI  - A chromosomal rearrangement in a child with severe speech and language disorder
      separates FOXP2 from a functional enhancer.
AB  - Mutations of FOXP2 in 7q31 cause a rare disorder involving speech apraxia,
      accompanied by expressive and receptive language impairments. A recent report
      described a child with speech and language deficits, and a genomic rearrangement
      affecting chromosomes 7 and 11. One breakpoint mapped to 7q31 and, although
      outside its coding region, was hypothesised to disrupt FOXP2 expression. We
      identified an element 2 kb downstream of this breakpoint with epigenetic
      characteristics of an enhancer. We show that this element drives reporter gene
      expression in human cell-lines. Thus, displacement of this element by
      translocation may disturb gene expression, contributing to the observed language
      phenotype. 

PMID- 26300978
TI  - Principal component gene set enrichment (PCGSE).
AB  - BACKGROUND: Although principal component analysis (PCA) is widely used for the
      dimensional reduction of biomedical data, interpretation of PCA results remains
      daunting. Most existing interpretation methods attempt to explain each principal
      component (PC) in terms of a small number of variables by generating approximate
      PCs with mainly zero loadings. Although useful when just a few variables dominate
      the population PCs, these methods can perform poorly on genomic data, where
      interesting biological features are frequently represented by the combined signal
      of functionally related sets of genes. While gene set testing methods have been
      widely used in supervised settings to quantify the association of groups of genes
      with clinical outcomes, these methods have seen only limited application for
      testing the enrichment of gene sets relative to sample PCs. RESULTS: We describe
      a novel approach, principal component gene set enrichment (PCGSE), for
      unsupervised gene set testing relative to the sample PCs of genomic data. The
      PCGSE method computes the statistical association between gene sets and
      individual PCs using a two-stage competitive gene set test. To demonstrate the
      efficacy of the PCGSE method, we use simulated and real gene expression data to
      evaluate the performance of various gene set test statistics and significance
      tests. CONCLUSIONS: Gene set testing is an effective approach for interpreting
      the PCs of high-dimensional genomic data. As shown using both simulated and real
      datasets, the PCGSE method can generate biologically meaningful and
      computationally efficient results via a two-stage, competitive parametric test
      that correctly accounts for inter-gene correlation.

PMID- 26300979
TI  - The value of thyroperoxidase as a prognostic factor for differentiated thyroid
      cancer -- a long-term follow-up study.
AB  - BACKGROUND: Thyroperoxidase (TPO) is a membrane-bound protein essential for the
      production of thyroid hormones; because of this, TPO expression may be impaired
      in selected thyroid diseases. The goal of this study is to analyze TPO immune
      expression in differentiated thyroid cancer, and to determine whether TPO has any
      prognostic value. METHODS: A total of 139 patients who required surgery due to a
      thyroid nodule with signs or symptoms suspicious for malignancy during their
      physical, ultrasound and/or cytology examination were consecutively selected for
      the study. A study of TPO immunohistochemical expression was carried out on these
      patients using the MoAb47 monoclonal antibody. In addition, cell proliferation
      marker Ki67 and tumor suppressor p53 were also measured for comparison. RESULTS:
      A total of 139 cases, 43 benign tumors, 42 papillary carcinomas, 38 follicular
      carcinomas, 8 undifferentiated carcinomas, and 8 sporadic medullary carcinomas
      were analyzed. The relationship between TPO expression and disease was
      statistically significant (p <0.001), and decreased with tumor dedifferentiation
      extent. Increased TPO expression in benign lesions as compared to decreased
      expression in papillary carcinomas and undifferentiated tumors is outstanding.
      Differences in TPO expression were observed in minimally invasive follicular
      carcinoma (MIFC) compared to widely invasive follicular carcinoma (WIFC). TPO
      expression decreases in undifferentiated malignancies in contrast with p53 and
      Ki67 expression, which increases in that setting. TPO, p53 and Ki67 expression
      was significantly related to TNM stage (p <0.001). Survival rate was 72 % after a
      20-year follow-up, and 100 % for subjects with higher TPO expression.
      CONCLUSIONS: TPO may be useful in confirming or ruling out benign diseases from
      differentiated thyroid carcinoma, with the exception of low-risk carcinoma such
      as MIFC. It could be used as a prognostic factor for differentiated thyroid
      cancer and patient follow-up, together with other markers.

PMID- 26300980
TI  - Tendon lengthening and fascia release for healing and preventing diabetic foot
      ulcers: a systematic review and meta-analysis.
AB  - BACKGROUND: Diabetic foot ulcers have a devastating impact on an individual's
      health-related quality of life and functional status. Additionally, diabetic foot
      ulcers impose a significant economic burden on our health care systems as a
      result of complications such as infection, hospitalisation and amputation. The
      current gold standard treatment for diabetic foot ulcers is total contact
      casting. However, the rate of ulcer recurrence is high, indicating the need for
      more effective long-term treatment options. Therefore, the aim of this study was
      to systematically identify, critique and evaluate all literature investigating
      the effectiveness of Achilles tendon lengthening, gastrocnemius recession and
      selective plantar fascia release in healing and preventing diabetic foot ulcers.
      REVIEW: Searches were conducted in MEDLINE, CINAHL, AMED, EMBASE and The Cochrane
      Library from the earliest available date to November 2014. Methodological quality
      of included studies was assessed using the Downs and Black checklist. Data from
      randomised-controlled trials were analysed using random effects meta-analysis.
      For all other studies, data were analysed descriptively. Eleven studies (614
      participants) were included in the review, with a median sample size of 29
      participants. Meta-analysis of two randomised-controlled trials found that there
      was no statistically significant difference between Achilles tendon lengthening
      or gastrocnemius recession and total contact casting for time to healing of
      diabetic foot ulcers (mean difference, MD, 8.22 days; 95 % CI, -18.99 to 35.43; P
      = 0.55; I (2)  = 34 %) and the rate of ulcers healed (risk ratio, RR, 1.06; 95 %
      CI, 0.94 to 1.20; P = 0.34; I (2)  = 41 %). The rate of ulcer recurrence was
      significantly lower following Achilles tendon lengthening or gastrocnemius
      recession than total contact casting (RR, 0.45; 95 % CI, 0.28 to 0.72; P < 0.001;
      I (2)  = 0 %). CONCLUSIONS: Achilles tendon lengthening and gastrocnemius
      recession appear to be effective surgical treatments for healing diabetic foot
      ulcers. The rate of ulcer recurrence was lower following Achilles tendon
      lengthening or gastrocnemius recession procedures compared to total contact
      casting treatment alone. Therefore, these surgical procedures may provide viable
      treatment options for the management and prevention of diabetic foot ulcers.
      Further rigorous randomised-controlled trials with longer follow-up are required
      to determine the long-term effectiveness and safety of these procedures.

PMID- 26300981
TI  - A consensus definition and rating scale for minimalist shoes.
AB  - BACKGROUND: While minimalist running shoes may have an influence on running
      biomechanics and on the incidence of overuse injuries, the term "minimalist" is
      currently used without standardisation. The objectives of this study were to
      reach a consensus on a standard definition of minimalist running shoes, and to
      develop and validate a rating scale that could be used to determine the degree of
      minimalism of running shoes, the Minimalist Index (MI). METHODS: For this
      modified Delphi study, 42 experts from 11 countries completed four electronic
      questionnaires on an optimal definition of minimalist shoes and on elements to
      include within the MI. Once MI was developed following consensus, 85 participants
      subjectively ranked randomly assigned footwear models from the most to the least
      minimalist and rated their degree of minimalism using visual analog scales (VAS),
      before evaluating the same footwear models using MI. A subsample of thirty
      participants reassessed the same shoes on another occasion. Construct validity
      and inter- and intra-rater reliability (intraclass correlation coefficients
      [ICC]; Gwet's AC1) of MI were evaluated. RESULTS: The following definition of
      minimalist shoes was agreed upon by 95 % of participants: "Footwear providing
      minimal interference with the natural movement of the foot due to its high
      flexibility, low heel to toe drop, weight and stack height, and the absence of
      motion control and stability devices". Characteristics to be included in MI were
      weight, flexibility, heel to toe drop, stack height and motion control/stability
      devices, each subscale carrying equal weighing (20 %) on final score. Total MI
      score was highly correlated with VAS (r = 0.91). A significant rank effect (p <
      0.001) confirmed the MI's discriminative validity. Excellent intra- and inter
      rater reliability was found for total MI score (ICC = 0.84-0.99) and for weight,
      stack height, heel to toe drop and flexibility subscales (AC1 = 0.82-0.99), while
      good inter-rater reliability was found for technologies (AC1 = 0.73). CONCLUSION:
      This standardised definition of minimalist shoes developed by an international
      panel of experts will improve future research on minimalist shoes and clinical
      recommendations. MI's adequate validity and reliability will allow distinguishing
      running shoes based on their degree of minimalism, and may help to decrease
      injuries related to footwear transition.

PMID- 26300982
TI  - Foot loading is different in people with and without pincer nails: a case control
      study.
AB  - BACKGROUND: Recent studies suggest that pincer nails are caused by lack of upward
      mechanical forces on the toe pad. However, clinically significant pincer nails
      are also often observed among healthy walkers. It was hypothesized that in these
      cases, the affected toes do not receive adequate physical stimulation from
      walking and loading. To test this, the gait characteristics of pincer nail cases
      were assessed by measuring plantar pressure during walking. METHODS: In total, 12
      bilateral pincer nail cases (24 affected feet) and 12 age- and sex-controlled
      healthy control subjects (24 ft) were enrolled in this prospective case-control
      study. Plantar pressure during free ambulation in both the barefoot and shod
      state was assessed using a digital pressure-plate system named S-Plate platform
      (Medicapteurs Co. France). First toe pressure and the frequencies of peak
      pressure in the first toe, metatarsal head, or other foot areas were calculated.
      RESULTS: In both the barefoot and shod state, the pincer nail group had
      significantly lower pressure on the first toe than the control group. In both the
      barefoot and shod state, the peak pressure area was mostly the metatarsal head
      area in the pincer nail group, whereas it was mostly the first toe area in the
      control group. Binomial logistic regression analysis revealed that peak pressure
      area was a significant risk factor for pincer nail development. CONCLUSION:
      Walking behavior appears to contribute to pincer nail development. Pincer nails
      of walkers could be treated by correcting the walking behaviour so that more
      pressure is placed on the toe pad.

PMID- 26300983
TI  - Visual analytics in cheminformatics: user-supervised descriptor selection for
      QSAR methods.
AB  - BACKGROUND: The design of QSAR/QSPR models is a challenging problem, where the
      selection of the most relevant descriptors constitutes a key step of the process.
      Several feature selection methods that address this step are concentrated on
      statistical associations among descriptors and target properties, whereas the
      chemical knowledge is left out of the analysis. For this reason, the
      interpretability and generality of the QSAR/QSPR models obtained by these feature
      selection methods are drastically affected. Therefore, an approach for
      integrating domain expert's knowledge in the selection process is needed for
      increase the confidence in the final set of descriptors. RESULTS: In this paper a
      software tool, which we named Visual and Interactive DEscriptor ANalysis
      (VIDEAN), that combines statistical methods with interactive visualizations for
      choosing a set of descriptors for predicting a target property is proposed.
      Domain expertise can be added to the feature selection process by means of an
      interactive visual exploration of data, and aided by statistical tools and
      metrics based on information theory. Coordinated visual representations are
      presented for capturing different relationships and interactions among
      descriptors, target properties and candidate subsets of descriptors. The
      competencies of the proposed software were assessed through different scenarios.
      These scenarios reveal how an expert can use this tool to choose one subset of
      descriptors from a group of candidate subsets or how to modify existing
      descriptor subsets and even incorporate new descriptors according to his or her
      own knowledge of the target property. CONCLUSIONS: The reported experiences
      showed the suitability of our software for selecting sets of descriptors with low
      cardinality, high interpretability, low redundancy and high statistical
      performance in a visual exploratory way. Therefore, it is possible to conclude
      that the resulting tool allows the integration of a chemist's expertise in the
      descriptor selection process with a low cognitive effort in contrast with the
      alternative of using an ad-hoc manual analysis of the selected descriptors.
      Graphical abstractVIDEAN allows the visual analysis of candidate subsets of
      descriptors for QSAR/QSPR. In the two panels on the top, users can interactively
      explore numerical correlations as well as co-occurrences in the candidate subsets
      through two interactive graphs.

PMID- 26300984
TI  - Optimizing drug-target interaction prediction based on random walk on
      heterogeneous networks.
AB  - BACKGROUND: Predicting novel drug-target associations is important not only for
      developing new drugs, but also for furthering biological knowledge by
      understanding how drugs work and their modes of action. As more data about drugs,
      targets, and their interactions becomes available, computational approaches have
      become an indispensible part of drug target association discovery. In this paper
      we apply random walk with restart (RWR) method to a heterogeneous network of
      drugs and targets compiled from DrugBank database and investigate the performance
      of the method under parameter variation and choice of chemical fingerprint
      methods. RESULTS: We show that choice of chemical fingerprint does not affect the
      performance of the method when the parameters are tuned to optimal values. We use
      a subset of the ChEMBL15 dataset that contains 2,763 associations between 544
      drugs and 467 target proteins to evaluate our method, and we extracted datasets
      of bioactivity <=1 and <=10 MUM activity cutoff. For 1 MUM bioactivity cutoff, we
      find that our method can correctly predict nearly 47, 55, 60% of the given drug
      target interactions in the test dataset having more than 0, 1, 2 drug target
      relations for ChEMBL 1 MUM dataset in top 50 rank positions. For 10 MUM
      bioactivity cutoff, we find that our method can correctly predict nearly 32.4,
      34.8, 35.3% of the given drug-target interactions in the test dataset having more
      than 0, 1, 2 drug target relations for ChEMBL 1 MUM dataset in top 50 rank
      positions. We further examine the associations between 110 popular top selling
      drugs in 2012 and 3,519 targets and find the top ten targets for each drug.
      CONCLUSIONS: We demonstrate the effectiveness and promise of the approach-RWR on
      heterogeneous networks using chemical features-for identifying novel drug target
      interactions and investigate the performance.

PMID- 26300985
TI  - PubChem atom environments.
AB  - BACKGROUND: Atom environments and fragments find wide-spread use in chemical
      information and cheminformatics. They are the basis of prediction models, an
      integral part in similarity searching, and employed in structure search
      techniques. Most of these methods were developed and evaluated on the relatively
      small sets of chemical structures available at the time. An analysis of fragment
      distributions representative of most known chemical structures was published in
      the 1970s using the Chemical Abstracts Service data system. More recently,
      advances in automated synthesis of chemicals allow millions of chemicals to be
      synthesized by a single organization. In addition, open chemical databases are
      readily available containing tens of millions of chemical structures from a
      multitude of data sources, including chemical vendors, patents, and the
      scientific literature, making it possible for scientists to readily access most
      known chemical structures. With this availability of information, one can now
      address interesting questions, such as: what chemical fragments are known today?
      How do these fragments compare to earlier studies? How unique are chemical
      fragments found in chemical structures? RESULTS: For our analysis, after hydrogen
      suppression, atoms were characterized by atomic number, formal charge, implicit
      hydrogen count, explicit degree (number of neighbors), valence (bond order sum),
      and aromaticity. Bonds were differentiated as single, double, triple or aromatic
      bonds. Atom environments were created in a circular manner focused on a central
      atom with radii from 0 (atom types) up to 3 (representative of ECFP_6 fragments).
      In total, combining atom types and atom environments that include up to three
      spheres of nearest neighbors, our investigation identified 28,462,319 unique
      fragments in the 46 million structures found in the PubChem Compound database as
      of January 2013. We could identify several factors inflating the number of
      environments involving transition metals, with many seemingly due to erroneous
      interpretation of structures from patent data. Compared to fragmentation
      statistics published 40 years ago, the exponential growth in chemistry is
      mirrored in a nearly eightfold increase in the number of unique chemical
      fragments; however, this result is clearly an upper bound estimate as earlier
      studies employed structure sampling approaches and this study shows that a
      relatively high rate of atom fragments are found in only a single chemical
      structure (singletons). In addition, the percentage of singletons grows as the
      size of the chemical fragment is increased. CONCLUSIONS: The observed growth of
      the numbers of unique fragments over time suggests that many chemically possible
      connections of atom types to larger fragments have yet to be explored by
      chemists. A dramatic drop in the relative rate of increase of atom environments
      from smaller to larger fragments shows that larger fragments mainly consist of
      diverse combinations of a limited subset of smaller fragments. This is further
      supported by the observed concomitant increase of singleton atom environments.
      Combined, these findings suggest that there is considerable opportunity for
      chemists to combine known fragments to novel chemical compounds. The comparison
      of PubChem to an older study of known chemical structures shows noticeable
      differences. The changes suggest advances in synthetic capabilities of chemists
      to combine atoms in new patterns. Log-log plots of fragment incidence show small
      numbers of fragments are found in many structures and that large numbers of
      fragments are found in very few structures, with nearly half being novel using
      the methods in this work. The relative decrease in the count of new fragments as
      a function of size further suggests considerable opportunity for more novel
      chemicals exists. Lastly, the differences in atom environment diversity between
      PubChem Substance and Compound showcase the effect of PubChem standardization
      protocols, but also indicate that a normalization procedure for atom types,
      functional groups, and tautomeric/resonance forms based on atom environments is
      possible. The complete sets of atom types and atom environments are supplied as
      supporting information.

PMID- 26300987
TI  - Gastric bypass surgery has a weight-loss independent effect on post-challenge
      serum glucose levels.
AB  - BACKGROUND: Gastric bypass surgery seems to have an effect on glucose metabolism
      beyond what is mediated through weight reduction. The magnitude of this effect on
      fasting and post-challenge glucose levels remains unknown. RESULTS: Morbidly
      obese subjects without known diabetes performed a 75 g oral glucose tolerance
      test before and after either gastric bypass surgery (n = 64) or an intensive
      lifestyle intervention programme (n = 55), ClinicalTrials.gov identifier
      NCT00273104. The age-adjusted effects of the therapeutic procedures and
      percentage weight change on fasting and 2-h glucose levels at 1 year were
      explored using multiple linear regression analysis. Mean (SD) serum fasting and 2
      h glucose levels at baseline did not differ between the surgery and lifestyle
      groups. Weight-loss after surgical treatment and lifestyle intervention was 30
      (8) and 9 (10) % (p < 0.001). At 1 year, fasting and 2-h glucose levels were
      significantly lower in the surgery group than in the lifestyle group, 4.7 (0.4)
      versus 5.4 (0.7) mmol/l and 3.4 (0.8) versus 6.0 (2.4) mmol/l, respectively (both
      p < 0.001). Gastric bypass and weight-loss had both independent glucose-lowering
      effects on 2-h glucose levels [B (95 % CI) 1.4 (0.6-2.3) mmol/l and 0.4 (0.1-0.7)
      mmol/l per 10 % weight-loss, respectively]. Fasting glucose levels were
      determined by weight change [0.2 (0.1-0.3) mmol/l per 10 % weight-loss] and not
      by type of treatment. CONCLUSIONS: Gastric bypass surgery has a clinically
      relevant glucose-lowering effect on post-challenge glucose levels which is
      seemingly not mediated through weight-loss alone.

PMID- 26300986
TI  - Effects of pentoxifylline on proteinuria and glucose control in patients with
      type 2 diabetes: a prospective randomized double-blind multicenter study.
AB  - BACKGROUND: Pentoxifylline is a methylxanthine derivative with significant anti
      inflammatory, anti-fibrotic, and anti-proliferative properties. Studies have
      shown that pentoxifylline may have renoprotective effects in patients with
      diabetic nephropathy. However, most of these studies were limited by small sample
      sizes. Therefore, we investigated whether pentoxifylline could reduce proteinuria
      in patients with diabetic nephropathy and residual proteinuria who received an
      angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor
      blocker (ARB). We also studied the effects of pentoxifylline on glycemic control,
      insulin resistance, and inflammatory parameters. METHODS: This was a prospective,
      randomized double-blind, placebo-controlled, multi-center study. A total of 174
      patients with type 2 diabetes and albuminuria (>30 mg/g of creatinine) who were
      taking the recommended dosage of ACEI or ARB for > 6 months and receiving
      conventional therapy for diabetes were randomly assigned to receive
      pentoxifylline (1200 mg, daily; n = 87) or a placebo (n = 87) for 6 months. The
      endpoints were the effects of pentoxifylline on proteinuria, renal function,
      glucose control, and inflammatory parameters. RESULTS: The percentage changes in
      proteinuria from baseline in the pentoxifylline and placebo groups were a
      decrease of 23 % and 4 %, respectively (p = 0.012). In addition, significant
      reductions in fasting plasma glucose, glycated hemoglobin, and insulin resistance
      according to the homeostasis model assessment were observed in the pentoxifylline
      group compared to those in the placebo group. However there was no significant
      difference in serum tumor necrosis factor (TNF)-alpha between the groups.
      CONCLUSIONS: Pentoxifylline therapy reduced proteinuria and improved glucose
      control and insulin resistance without significant change of serum TNF-alpha in
      patients with type 2 diabetic nephropathy. Therefore, pentoxifylline is a
      potential therapeutic alternative for treating diabetes and diabetic nephropathy.
      TRIAL REGISTRATION: NCT01382303.

PMID- 26300988
TI  - Speech motor planning and execution deficits in early childhood stuttering.
AB  - BACKGROUND: Five to eight percent of preschool children develop stuttering, a
      speech disorder with clearly observable, hallmark symptoms: sound repetitions,
      prolongations, and blocks. While the speech motor processes underlying stuttering
      have been widely documented in adults, few studies to date have assessed the
      speech motor dynamics of stuttering near its onset. We assessed fundamental
      characteristics of speech movements in preschool children who stutter and their
      fluent peers to determine if atypical speech motor characteristics described for
      adults are early features of the disorder or arise later in the development of
      chronic stuttering. METHODS: Orofacial movement data were recorded from 58
      children who stutter and 43 children who do not stutter aged 4;0 to 5;11 (years;
      months) in a sentence production task. For single speech movements and multiple
      speech movement sequences, we computed displacement amplitude, velocity, and
      duration. For the phrase level movement sequence, we computed an index of
      articulation coordination consistency for repeated productions of the sentence.
      RESULTS: Boys who stutter, but not girls, produced speech with reduced amplitudes
      and velocities of articulatory movement. All children produced speech with
      similar durations. Boys, particularly the boys who stuttered, had more variable
      patterns of articulatory coordination compared to girls. CONCLUSIONS: This study
      is the first to demonstrate sex-specific differences in speech motor control
      processes between preschool boys and girls who are stuttering. The sex-specific
      lag in speech motor development in many boys who stutter likely has significant
      implications for the dramatically different recovery rates between male and
      female preschoolers who stutter. Further, our findings document that atypical
      speech motor development is an early feature of stuttering.

PMID- 26300989
TI  - Dual EZH2 and EHMT2 histone methyltransferase inhibition increases biological
      efficacy in breast cancer cells.
AB  - BACKGROUND: Many cancers show aberrant silencing of gene expression and
      overexpression of histone methyltransferases. The histone methyltransferases
      (HKMT) EZH2 and EHMT2 maintain the repressive chromatin histone methylation marks
      H3K27me and H3K9me, respectively, which are associated with transcriptional
      silencing. Although selective HKMT inhibitors reduce levels of individual
      repressive marks, removal of H3K27me3 by specific EZH2 inhibitors, for instance,
      may not be sufficient for inducing the expression of genes with multiple
      repressive marks. RESULTS: We report that gene expression and inhibition of
      triple negative breast cancer cell growth (MDA-MB-231) are markedly increased
      when targeting both EZH2 and EHMT2, either by siRNA knockdown or pharmacological
      inhibition, rather than either enzyme independently. Indeed, expression of
      certain genes is only induced upon dual inhibition. We sought to identify
      compounds which showed evidence of dual EZH2 and EHMT2 inhibition. Using a cell
      based assay, based on the substrate competitive EHMT2 inhibitor BIX01294, we have
      identified proof-of-concept compounds that induce re-expression of a subset of
      genes consistent with dual HKMT inhibition. Chromatin immunoprecipitation
      verified a decrease in silencing marks and an increase in permissive marks at the
      promoter and transcription start site of re-expressed genes, while Western
      analysis showed reduction in global levels of H3K27me3 and H3K9me3. The compounds
      inhibit growth in a panel of breast cancer and lymphoma cell lines with low to
      sub-micromolar IC50s. Biochemically, the compounds are substrate competitive
      inhibitors against both EZH2 and EHMT1/2. CONCLUSIONS: We have demonstrated that
      dual inhibition of EZH2 and EHMT2 is more effective at eliciting biological
      responses of gene transcription and cancer cell growth inhibition compared to
      inhibition of single HKMTs, and we report the first dual EZH2-EHMT1/2 substrate
      competitive inhibitors that are functional in cells.

PMID- 26300990
TI  - Triage of high-risk human papillomavirus-positive women by methylated POU4F3.
AB  - BACKGROUND: Insufficient specificity of the high-risk human papillomavirus
      (hrHPV) assay in primary cervical cancer screening results in unnecessary
      referral. Additional assays to triage hrHPV-positive women are needed to improve
      molecular cervical cancer screening. DNA methylation is a promising biomarker in
      cervical cancer. We evaluated the clinical performance of potentially methylated
      genes as a triage assay for hrHPV-positive women. RESULTS: We conducted a
      retrospective hospital-based case-control study in Taiwan. Cervical scrapings
      were collected before colposcopy for hrHPV testing and quantitative methylation
      specific PCR (QMSP) of 16 genes. Five genes, POU4F3, HS3ST2, AJAP1, PAX1, and
      SOX1, were prioritized for the clinical performance to triage hrHPV-positive
      women. Two hundred cervical scrapings were randomly classified into a training
      set (n = 111) and testing set (n = 89). All samples were tested for hrHPV using a
      Hybrid Capture II (HCII) assay. HrHPV-positive women were subjected to DNA
      methylation analysis by QMSP. In the training set, the receiver operating
      characteristic (ROC) curves defined the optimal methylation index (M-index)
      cutoff values for discriminating CIN3(+) from CIN1/normal, which then were
      applied to the testing set. Among the five genes, POU4F3 revealed the highest
      area under the ROC curve (AUC) (0.86; 95 % CI, 0.78-0.95) in detecting CIN3(+).
      In the testing set, POU4F3 revealed the best clinical performance in triage of
      hrHPV-positive women with a sensitivity of 74 % and specificity of 89 % for
      detecting CIN3(+). CONCLUSIONS: POU4F3 methylation analysis is a potential
      molecular tool for triage in detecting CIN3(+) in hrHPV-positive women. The
      combined use of broad-spectrum HPV assay and POU4F3 methylation analysis as a new
      generation of molecular cervical cancer screening warrants further population
      based study.

PMID- 26300991
TI  - Global analysis of DNA methylation in hepatocellular carcinoma by a liquid
      hybridization capture-based bisulfite sequencing approach.
AB  - BACKGROUND: Epigenetic alterations, such as aberrant DNA methylation of promoter
      and enhancer regions, which lead to atypical gene expression, have been
      associated with carcinogenesis. In hepatocellular carcinoma (HCC), genome-wide
      analysis of methylation has only recently been used. For a better understanding
      of hepatocarcinogenesis, we applied an even higher resolution analysis of the
      promoter methylome to identify previously unknown regions and genes
      differentially methylated in HCC. RESULTS: Optimized liquid hybridization capture
      based bisulfite sequencing (LHC-BS) was developed to quantitatively analyze 1.86
      million CpG sites in individual samples from eight pairs of HCC and adjacent
      tissues. By linking the differentially methylated regions (DMRs) in promoters to
      the differentially expressed genes (DEGs), we identified 12 DMR-associated genes.
      We further utilized Illumina MiSeq combining the bisulfite sequencing PCR
      approach to validate the 12 candidate genes. Analysis of an additional 78 HCC
      pairs on the Illumina MiSeq platform confirmed that 7 genes showed either
      promoter hyper-methylation (SMAD6, IFITM1, LRRC4, CHST4, and TBX15) or hypo
      methylation (CCL20 and NQO1) in HCC. CONCLUSIONS: Novel methylome profiling
      provides a cost-efficient approach to identifying candidate genes in human HCC
      that may contribute to hepatocarcinogenesis. Our work provides further
      information critical for understanding the epigenetic processes underlying
      tumorigenesis and development of HCC.

PMID- 26300993
TI  - 5-Carboxylcytosine levels are elevated in human breast cancers and gliomas.
AB  - BACKGROUND: DNA methylation (5-methylcytosine (5mC)) patterns are often altered
      in cancers. Ten-eleven translocation (Tet) proteins oxidise 5mC to 5
      hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine
      (5caC). In addition to their presumptive specific biological roles, these
      oxidised forms of 5mC may serve as intermediates in demethylation process.
      According to several reports, 5hmC levels are strongly decreased in cancers;
      however, the distribution of 5fC and 5caC in malignant tissue has not been
      studied. FINDINGS: Here, we examine the levels of 5hmC and 5caC in 28 samples of
      normal breast tissue, 59 samples of invasive human breast cancer and 74 samples
      of gliomas using immunochemistry. In agreement with previous reports, we show
      that 71 % of normal breast samples exhibit strong 5hmC signal, compared with only
      18 % of breast cancer samples with equivalent levels of 5hmC staining.
      Unexpectedly, although 5caC is not detectable in normal breast tissue, 27 % of
      breast cancer samples exhibit significant staining for this modification (p <
      0.001). Surprisingly, the presence of immunochemically detectable 5caC is not
      associated with the intensity of 5hmC signal in breast cancer tissue. In gliomas,
      we show that 5caC is detectable in 45 % of tumours. CONCLUSIONS: We demonstrate
      that, unlike 5hmC, the levels of 5caC are elevated in a proportion of breast
      cancers and gliomas. Our results reveal another level of complexity to the cancer
      epigenome, suggesting that active demethylation and/or 5caC-dependent
      transcriptional regulation are pre-activated in some tumours and may contribute
      to their pathogenesis. Larger studies to evaluate the clinicopathological
      significance of 5caC in cancers are warranted.

PMID- 26300992
TI  - The placenta: phenotypic and epigenetic modifications induced by Assisted
      Reproductive Technologies throughout pregnancy.
AB  - Today, there is growing interest in the potential epigenetic risk related to
      assisted reproductive technologies (ART). Much evidence in the literature
      supports the hypothesis that adverse pregnancy outcomes linked to ART are
      associated with abnormal trophoblastic invasion. The aim of this review is to
      investigate the relationship between epigenetic dysregulation caused by ART and
      subsequent placental response. The dialogue between the endometrium and the
      embryo is a crucial step to achieve successful trophoblastic invasion, thus
      ensuring a non-complicated pregnancy and healthy offspring. However, as described
      in this review, ART could impair both actors involved in this dialogue. First,
      ART may induce epigenetic defects in the conceptus by modifying the embryo
      environment. Second, as a result of hormone treatments, ART may impair
      endometrial receptivity. In some cases, it results in embryonic growth arrest
      but, when the development of the embryo continues, the placenta could bring
      adaptive responses throughout pregnancy. Amongst the different mechanisms,
      epigenetics, especially thanks to a finely tuned network of imprinted genes
      stimulated by foetal signals, may modify nutrient transfer, placental growth and
      vascularization. If these coping mechanisms are overwhelmed, improper maternal
      foetal exchanges occur, potentially leading to adverse pregnancy outcomes such as
      abortion, preeclampsia or intra-uterine growth restriction. But in most cases,
      successful placental adaptation enables normal progress of the pregnancy.
      Nevertheless, the risks induced by these modifications during pregnancy are not
      fully understood. Metabolic diseases later in life could be exacerbated through
      the memory of epigenetic adaptation mechanisms established during pregnancy.
      Thus, more research is still needed to better understand abnormal interactions
      between the embryo and the milieu in artificial conditions. As trophectoderm
      cells are in direct contact with the environment, they deserve to be studied in
      more detail. The ultimate goal of these studies will be to render ART protocols
      safer. Optimization of the environment will be the key to improving the dialogue
      between the endometrium and embryo, so as to ensure that placentation after ART
      is similar to that following natural conception. 

PMID- 26300994
TI  - Detection of nasopharyngeal carcinoma in Morocco (North Africa) using a multiplex
      methylation-specific PCR biomarker assay.
AB  - BACKGROUND: Silencing of tumor suppressor genes (TSGs) or activation of oncogenes
      by, e.g., aberrant promoter methylation, may be early events during
      carcinogenesis. The methylation status of such genes can be used for early
      detection of cancer. We are pursuing this approach in our efforts to develop
      markers for early detection and follow-up of nasopharyngeal carcinoma (NPC). We
      set out to develop this approach to allow identification of NPC from Morocco and
      then also compared with NPC samples from different geographical locations and
      different ethnicity with different NPC incidences, Epstein-Barr virus (EBV)
      prevalence, and environments. RESULTS: By multiplex methylation-specific PCR
      (MMSP), multiple relevant genes can be detected simultaneously, to achieve high
      sensitivity and specificity. The strong association of EBV with NPC is also very
      useful in such an approach. We have initially screened for 12 potential marker
      genes including EBV genes coding for EBV nuclear antigen 1 (EBNA1) and latent
      membrane protein-1 (LMP1) and ten potential TSGs obtained from previously
      published data. The resulting assay included EBNA1, LMP1, and three cellular
      TSGs: ITGA9, RASSF1A, and P16. We evaluated this assay on 64 NPC patient biopsies
      from Morocco, Italy, and China compared to deoxyribonucleic acid (DNA) from 20
      nasopharyngeal control tissues. In the Moroccan NPC cohort (n = 44), prevalence
      of the EBNA1 gene showed the highest sensitivity (36/44; 82 %) with 94 %
      specificity. Out of eight (18 %) EBNA1 negative Moroccan samples, only three were
      positive for at least one methylated cellular gene. By detection of cellular
      marker genes, the sensitivity increased from 82 to 89 % (39/44). In the whole
      material of 64 biopsies from three geographical locations, at least any one
      marker (viral or cellular) could be detected in 91 % of biopsies with 90 %
      specificity. In a pilot evaluating assay performance on serum DNA from NPC and
      controls including samples from Italy (n = 11) and China (n = 5), at least any
      one marker from the MMSP assay could be detected in 88 %, but the specificity was
      only 50 %. CONCLUSIONS: An MMSP assay has the potential for detection of NPC by
      screening in high-risk populations. Serum-derived DNA seems not as good as
      earlier published NPC swab DNA for screening purpose.

PMID- 26300995
TI  - Ethics, Risk and Benefits Associated with Different Applications of
      Nanotechnology: a Comparison of Expert and Consumer Perceptions of Drivers of
      Societal Acceptance.
AB  - Examining those risk and benefit perceptions utilised in the formation of
      attitudes and opinions about emerging technologies such as nanotechnology can be
      useful for both industry and policy makers involved in their development,
      implementation and regulation. A broad range of different socio-psychological and
      affective factors may influence consumer responses to different applications of
      nanotechnology, including ethical concerns. A useful approach to identifying
      relevant consumer concerns and innovation priorities is to develop predictive
      constructs which can be used to differentiate applications of nanotechnology in a
      way which is meaningful to consumers. This requires elicitation of attitudinal
      constructs from consumers, rather than measuring attitudes assumed to be
      important by the researcher. Psychological factors influencing societal responses
      to 15 applications of nanotechnology drawn from different application areas (e.g.
      medicine, agriculture and environment, food, military, sports, and cosmetics)
      were identified using repertory grid method in conjunction with generalised
      Procrustes analysis. The results suggested that people differentiate
      nanotechnology applications based on the extent to which they perceive them to be
      beneficial, useful, necessary and important. The benefits may be offset by
      perceived risks focusing on fear and ethical concerns. Compared to an earlier
      expert study on societal acceptance of nanotechnology, consumers emphasised
      ethical issues compared to experts but had less concern regarding potential
      physical contact with the product and time to market introduction. Consumers
      envisaged fewer issues with several applications compared to experts, in
      particular food applications.

PMID- 26300996
TI  - Cumulative BRCA mutation analysis in the Greek population confirms that
      homogenous ethnic background facilitates genetic testing.
AB  - Screening for BRCA 1 and BRCA 2 mutations has long moved from the research lab to
      the clinic as a routine clinical genetic testing. BRCA molecular alteration
      pattern varies among ethnic groups which makes it already a less straightforward
      process to select the appropriate mutations for routine genetic testing on the
      basis of known clinical significance. The present report comprises an in depth
      literature review of the so far reported BRCA 1 and BRCA 2 molecular alterations
      in Greek families. Our analysis of Greek cumulative BRCA 1 and 2 molecular data,
      produced by several independent groups, confirmed that six recurrent deleterious
      mutations account for almost 60 % and 70 % of all BRCA 1 and 2 and BRCA 1
      mutations, respectively. As a result, it makes more sense to perform BRCA
      mutation analysis in the clinic in two sequential steps, first conventional
      analysis for the six most prevalent pathogenic mutations and if none identified,
      a second step of New Generation Sequencing-based whole genome or whole exome
      sequencing would follow. Our suggested approach would enable more clinically
      meaningful, considerably easier and less expensive BRCA analysis in the Greek
      population which is considered homogenous. 

PMID- 26300998
TI  - In Response to the Article "CT of Hepatic Sarcoidosis: Small Nodular Lesions
      Simulating Metastatic Disease". Pol J Radiol, 2015; 80: 178-180.

PMID- 26300997
TI  - Next-generation sequencing for genetic testing of familial colorectal cancer
      syndromes.
AB  - BACKGROUND: Genetic screening in families with high risk to develop colorectal
      cancer (CRC) prevents incurable disease and permits personalized therapeutic and
      follow-up strategies. The advancement of next-generation sequencing (NGS)
      technologies has revolutionized the throughput of DNA sequencing. METHODS: A
      series of 16 probands for either familial adenomatous polyposis (FAP; 8 cases) or
      hereditary nonpolyposis colorectal cancer (HNPCC; 8 cases) were investigated for
      intragenic mutations in five CRC familial syndromes-associated genes (APC, MUTYH,
      MLH1, MSH2, MSH6) applying both a custom multigene Ion AmpliSeq NGS panel and
      conventional Sanger sequencing. RESULTS: Fourteen pathogenic variants were
      detected in 13/16 FAP/HNPCC probands (81.3 %); one FAP proband presented two co
      existing pathogenic variants, one in APC and one in MUTYH. Thirteen of these 14
      pathogenic variants were detected by both NGS and Sanger, while one MSH2 mutation
      (L280FfsX3) was identified only by Sanger sequencing. This is due to a limitation
      of the NGS approach in resolving sequences close or within homopolymeric
      stretches of DNA. To evaluate the performance of our NGS custom panel we assessed
      its capability to resolve the DNA sequences corresponding to 2225 pathogenic
      variants reported in the COSMIC database for APC, MUTYH, MLH1, MSH2, MSH6. Our
      NGS custom panel resolves the sequences where 2108 (94.7 %) of these variants
      occur. The remaining 117 mutations reside inside or in close proximity to
      homopolymer stretches; of these 27 (1.2 %) are imprecisely identified by the
      software but can be resolved by visual inspection of the region, while the
      remaining 90 variants (4.0 %) are blind spots. In summary, our custom panel would
      miss 4 % (90/2225) of pathogenic variants that would need a small set of Sanger
      sequencing reactions to be solved. CONCLUSIONS: The multiplex NGS approach has
      the advantage of analyzing multiple genes in multiple samples simultaneously,
      requiring only a reduced number of Sanger sequences to resolve homopolymeric DNA
      regions not adequately assessed by NGS. The implementation of NGS approaches in
      routine diagnostics of familial CRC is cost-effective and significantly reduces
      diagnostic turnaround times.

PMID- 26300999
TI  - Trifurcation of the Left Common Carotid Artery.
AB  - BACKGROUND: Trifurcation of the common carotid artery is an unusual variation.
      CASE REPORT: We report a case of left common carotid artery trifurcation in a 74
      year-old man. The left common carotid artery divided into the internal carotid,
      external carotid and facial arteries. Herein, the anatomy of the carotid arteries
      and the Doppler sonography and CT angiography findings of the left common carotid
      artery trifurcation were described with images. CONCLUSIONS: The variations of
      the carotid arteries should be known to avoid and reduce the complications during
      the invasive procedures.

PMID- 26301001
TI  - Anatomic Landmarks of the Distal Radioulnar Joint.
AB  - HYPOTHESIS: Using Lister's tubercle and the ulnar styloid as landmarks, accurate
      localization of the distal radioulnar joint can be achieved without the need for
      an image-guided approach. METHODS: Cadaveric dissection of 16 upper extremities
      was performed to measure the relationships between the ulnar styloid, Lister's
      tubercle, and the distal radioulnar joint. In each specimen, the location of the
      distal radioulnar joint (point A) in relation to Lister's tubercle and the ulnar
      styloid was determined as follows: (1) the perpendicular distance between the
      distal radioulnar joint and ulnar styloid-Lister's tubercle was measured; (2)
      with A' marking the intersection of this distance and the ulnar styloid-Lister's
      tubercle line, the location of the distal radioulnar joint along the ulnar
      styloid-Lister's tubercle axis was determined by comparing ulnar styloid-A' and
      A'-Lister's tubercle with ulnar styloid-Lister's tubercle. RESULTS: The mean
      distance between ulnar styloid-Lister's tubercle was 4.3 +/- 0.4 cm. The mean
      perpendicular distance between the distal radioulnar joint and the ulnar styloid
      Lister's tubercle line was 0.2 +/- 0.1 cm proximal to the ulnar styloid-Lister's
      tubercle line. The ratio of ulnar styloid-A' and A'-Lister's tubercle to ulnar
      styloid-Lister's tubercle was 0.5 +/- 0.03 and 0.5 +/- 0.03, respectively.
      CONCLUSIONS: Simple relationships between the ulnar styloid and Lister's tubercle
      serve as reliable landmarks for locating the distal radioulnar joint. The distal
      radioulnar joint is centered about the midpoint of the ulnar styloid-Lister's
      tubercle axis and slightly proximal to it. This may improve the accuracy and
      efficacy of corticosteroid injections in the treatment of distal radioulnar joint
      arthritis without the need for image guidance.

PMID- 26301002
TI  - Three-Dimensional Printing Surgical Applications.
AB  - INTRODUCTION: Three-dimensional printing, a technology used for decades in the
      industrial field, gains a lot of attention in the medical field for its potential
      benefits. With advancement of desktop printers, this technology is accessible and
      a lot of research is going on in the medical field. OBJECTIVE: To evaluate its
      application in surgical field, which may include but not limited to surgical
      planning, surgical education, implants, and prosthesis, which are the focus of
      this review. METHODS: Research was conducted by searching PubMed, Web of science,
      and other reliable sources. We included original articles and excluded articles
      based on animals, those more than 10 years old, and those not in English. These
      articles were evaluated, and relevant studies were included in this review.
      DISCUSSION: Three-dimensional printing shows a potential benefit in surgical
      application. Printed implants were used in patient in a few cases and show
      successful results; however, longer follow-up and more trials are needed.
      Surgical and medical education is believed to be more efficient with this
      technology than the current practice. Printed surgical instrument and surgical
      planning are also believed to improve with three-dimensional printing.
      CONCLUSION: Three-dimensional printing can be a very powerful tool in the near
      future, which can aid the medical field that is facing a lot of challenges and
      obstacles. However, despite the reported results, further research on larger
      samples and analytical measurements should be conducted to ensure this
      technology's impact on the practice.

PMID- 26301000
TI  - Diagnosis of Fusarium Infections: Approaches to Identification by the Clinical
      Mycology Laboratory.
AB  - Infections caused by the genus Fusarium have emerged over the past decades and
      range from onychomycosis and keratitis in healthy individuals to deep and
      disseminated infections with high mortality rates in immune-compromised patients.
      As antifungal susceptibility can differ between the different Fusarium species,
      identification at species level is recommended. Several clinical observations as
      hyaline hyphae in tissue, necrotic lesions in the skin and positive blood tests
      with fungal growth or presence of fungal cell wall components may be the first
      hints for fusariosis. Many laboratories rely on morphological identification, but
      especially multi-locus sequencing proves better to discriminate among members of
      the species complexes involved in human infection. DNA-based diagnostic tools
      have best discriminatory power when based on translation elongation factor 1
      alpha or the RNA polymerase II second largest subunit. However, assays based on
      the detection of other fusarial cell compounds such as peptides and cell wall
      components may also be used for identification. The purpose of this review is to
      provide an overview and a comparison of the different tools currently available
      for the diagnosis of fusariosis.

PMID- 26301003
TI  - [Evaluation of antiretroviral therapy on mother to child transmission HIV in HIV
      1 positive pregnant women: case of St. Camillus Medical Center in Ouagadougou,
      Burkina Faso].

PMID- 26301004
TI  - [Complete androgen insensitivity syndrome: report of two cases and review of
      literature].

PMID- 26301005
TI  - [Assessment of the severity of the condition of patients admitted to intensive
      care by measuring CRP].

PMID- 26301006
TI  - [Nail nodule in athletes: think of subungual exostosis].

PMID- 26301007
TI  - Effectiveness of Ng'adakarin Bamocha model in improving access to ante-natal and
      delivery services among nomadic pastoralist communities of Turkana West and
      Turkana North Sub-Counties of Kenya.
AB  - INTRODUCTION: Access to maternal and child health care services among the nomadic
      pastoralists community in Kenya and African continent in general is unacceptably
      low. In Turkana, only 18.1% of the women had seen a nurse or a midwife for
      antenatal care during pregnancy while only 1.3% of pregnant women reported
      delivery at health facilities in 2005. Ng'adakarin BAMOCHA model, based on
      migratory routes of the Turkana pastoralists and container clinics was adopted in
      2007 to improve access to maternal and child health services by the nomads.
      METHODS: A cross-sectional study design was used to establish the effectiveness
      of Ng'adakarin BAMOCHA model on accessibility and uptake of ante-natal care and
      delivery services. A total of 360 households and 400 households were interviewed
      for pre-intervention and post-intervention respectively. The study compared the
      pre-intervention and post-intervention findings. Structured questionnaires and
      focus group discussion were used for data collection. RESULTS: There was no
      improvement in the fourth ante-natal care visits between pre-intervention and
      post-intervention groups at 119(51.5%) and 111(41.9%) respectively (p < 0.05).
      Knowledge of the community on the importance of ANC visits improved from 60%-72%
      with significance level of p < 0.05. There was a significant increase 6%-17% of
      deliveries under a skilled health worker (p < 0.05). TBA assisted deliveries
      increased from 7.5%- 20.2% with a p < 0.05. There was significant reduction in
      home deliveries from 89.5%-79.5% with a p < 0.05. CONCLUSION: The Ng'adakarin
      Bamocha model had a positive effect on the improving maternal health care among
      the nomadic pastoralist community in Turkana.

PMID- 26301008
TI  - Ebola a reality of modern Public Health; need for Surveillance, Preparedness and
      Response Training for Health Workers and other multidisciplinary teams: a case
      for Uganda.
AB  - INTRODUCTION: West Africa is experiencing the largest ever reported Ebola
      outbreak. Over 20,000 people have been infected of which about 9000 have died. It
      is possible that lack of community understanding of the epidemic and lack of
      institutional memory and inexperienced health workers could have led to the rapid
      spread of the disease. In this paper, we share Uganda's experiences on how the
      capacity of health workers and other multidisciplinary teams can be improved in
      preparing and responding to Ebola outbreaks. METHODS: Makerere University School
      of Public Health in collaboration with the Ministry of Health and the African
      Field Epidemiology Network (AFENET), trained health care workers and other
      multidisciplinary teams from six border districts of Uganda so as to increase
      their alertness and response capabilities towards Ebola. We used participatory
      training methods to impart knowledge and skills and guided participants to
      develop district epidemic response plans. Communities were sensitized about Ebola
      through mass media, IEC materials, and infection control and prevention materials
      were distributed in districts. RESULTS: We trained 210 health workers and 120
      other multidisciplinary team members on Ebola surveillance, preparedness and
      response. Evaluation results demonstrated a gain in knowledge and skills.
      Communities were sensitized about Ebola and Districts received person protective
      equipments and items for infection prevention. Epidemic Preparedness and Response
      plans were also developed. CONCLUSION: Training of multidisciplinary teams
      improves the country's preparedness, alertness and response capabilities in
      controlling Ebola. West African countries experiencing Ebola outbreaks could draw
      lessons from the Uganda experience to contain the outbreak.

PMID- 26301009
TI  - [Compartment syndrome of the arm: an unusual complication of carbon monoxide
      poisoning].

PMID- 26301010
TI  - Prevalence, sociodemographic features and risk factors of Hepatitis B virus
      infection among pregnant women in Southwestern Nigeria.
AB  - INTRODUCTION: Hepatitis B virus is responsible for 50%-80% of Hepatocellular
      carcinoma cases worldwide. In Nigeria, vertical transmission remains a major
      route of Hepatitis B virus infection. Primary (vaccines and post-exposure
      prophylaxis) and secondary prevention of HBV transmission by appropriate sexual
      and sanitary practices are not yet optimal in the country yet measures for early
      detection (serological, molecular) and treatment of infected pregnant women is
      not a practice. This study aimed at identifying the prevalence and risk factors
      for Hepatitis B virus infection among pregnant women in Ibadan, Southwestern
      Nigeria. METHODS: A cross-sectional study was done at the Ante-natal clinic of
      the University College Hospital Ibadan. One hundred and eighty pregnant women
      were recruited from March to August 2013, and tested for Hepatitis B surface
      antigen (BIORAD FRANCE) using third generation ELISA, as well as HIV-1 and 2
      using Uni-Gold Recombigen and ALERE determine (a rapid immunoassay designed to
      detect antibodies to HIV 1 and/or 2). Positive HBsAg samples were tested for
      Hepatitis B envelope antigen, antibody and Hepatitis B core antibody (DIAPRO
      Italy) while serum HBV DNA was detected using PCR. Data were obtained using
      questionnaires to establish and analysis was performed using SPSS version 20.
      RESULTS: The seroprevalence of HBsAg was 8.3% out of which 26.7% were positive
      for HBeAg, 53.3% had HBeAb, 20% had neither HBeAg nor HBeAb, 100% had total HBcAb
      and 86.7% had HBV DNA in their serum. The mean age was 32.1 years, the highest
      HBV infection rate occurred in 25-29 year age group. Multiple sexual partners (OR
      3.987, P- value=0.026) and early age at sexual debut (OR 11.996, P- value=0.022)
      were independent risk factors for HBV infection. CONCLUSION: Hepatitis B virus
      infection is of high endemicity in Nigeria thus early detection, treatment of
      infected pregnant women, immunoprophylaxis for exposed newborns and surveillance
      for those with chronic infection is essential. Health education programs on
      prevention and control measures must be instituted.

PMID- 26301012
TI  - [Von Recklinghausen disease complicated with head and neck plexiform
      neurofibromas].

PMID- 26301011
TI  - Does intranasal fentanyl provide efficient analgesia for renal colic in adults?
AB  - INTRODUCTION: Intranasal fentanyl provides rapid and powerful analgesia which is
      particularly interesting in patients without intravenous access. We propose to
      use it for analgesia in adults presenting renal colics. METHODS: A prospective
      study was conducted from the 2nd January to February 2013 in our emergency
      department. Patients aged up to 18 years old who presented with renal colic were
      included in this audit. Patients were excluded if they had loss of consciousness,
      cognitive impairment, acute or chronic nasal problems. A formal written consent
      was obtained from patients. The research team was alerted by medical and nursing
      staff. A member of the research team would check with medical or nursing staff
      whether administration of Intra nasal (IN) fentanyl was required. It was
      administered at a pre-calculated dose of 1.5 mg/kg and 50 mg/ml concentration was
      used. Data was prospectively collected by one of the researchers at various
      intervals during the patient's presentation and recorded on a pre-formatted data
      sheet. Pain scores were collected at 5, 15, 30, 45 and 60 minutes following IN
      fentanyl using a visual analogue scale pain. Observations routinely collected for
      patients receiving IV opiates and any adverse events were also recorded. RESULTS:
      23 eligible patients were enrolled; median age was 51,3 years. 47,8% were women
      and the mean weight was 73 kg. Median dose of IN fentanyl was 106 MUg. Two
      patients have required morphinic analgesia despite having received adapted dose
      of IN fentanyl. The initial pain scores before IN fentanyl were high with a
      median of 82,2 mm (59-100). Five minutes after IN fentanyl administration the
      median pain score dropped to 48 mm(36-63) and achieved the lowest score of 8mm(0
      22) at 30 min. Pain scores were significantly lower at 5 min (P < 0.001) and at
      all subsequent time points (P < 0.001). No side effects were recorded.
      CONCLUSION: Intranasal fentanyl seems to be efficient for analgesia in adult
      patients with renal colic.

PMID- 26301013
TI  - [Mediastinal thymoma: a diagnosis to not to ignore].

PMID- 26301014
TI  - [Behcet syndrome associated with IgA nephropathy].

PMID- 26301015
TI  - [Giant aneurysm of the pulmonary artery revealing Behcet syndrome].

PMID- 26301016
TI  - [Factors associated with non-adherence of adults infected with HIV on
      antiretroviral therapy in a referral hospital in Douala].

PMID- 26301017
TI  - [Cervical burns sequelae: epidemiological, clinical and therapeutic aspects in
      Morocco].

PMID- 26301018
TI  - [Radio-anatomical results of total knee prostheses (about 30 cases)].

PMID- 26301019
TI  - [A rare cause of septic shock in diabetic: emphysematous cystitis complicated
      with bladder rupture].

PMID- 26301020
TI  - [About a rare form of myositis ossificans progressiva of Munchmeyer].

PMID- 26301021
TI  - [Metastatic tumors of the iris and ciliary body of a lung cancer].

PMID- 26301022
TI  - [Erlenmeyer flask deformity of the femur in Gaucher disease].

PMID- 26301023
TI  - [Family Juvenile Systemic Lupus: about two families].

PMID- 26301024
TI  - Initial Clinical Experience with a New Self-Expanding Nitinol Microstent for the
      Treatment of Wide-Neck Intracranial Cerebral Aneurysms: The Acandis Acclino
      Stent.
AB  - BACKGROUND AND PURPOSE: The Acclino is a laser-cut closed-cell microstent
      composed of nitinol. It was developed for stent-assisted coiling of wide-neck
      intracranial aneurysms. The key feature of the stent is its deployability via low
      profile microcatheters with an inner diameter of 0.0165 inch, which are also
      suited for coil deployment. The objective of this study was to evaluate the
      safety and feasibility as well as the immediate and mid-term results of this new
      device. MATERIALS AND METHODS: Our database was screened for all Acclino-based
      stent-assisted intracranial coil embolizations since its introduction to the
      European market in June 2012. Case files and imaging data were retrospectively
      analyzed for angiographical and clinical outcome parameters, including immediate
      and mid-term modified Raymond-Roy aneurysm occlusion classification (RROC) rates
      and procedural complications. RESULTS: Fourteen patients comprising 14 aneurysms
      (9 unruptured and 5 ruptured) were treated with the Acclino. All except for a
      dissecting one were wide-neck saccular aneurysms. Immediate complete occlusion
      (RROC1) was observed in 8/14 cases (57%), a residual neck (RROC2) in 4/14 (29%),
      and a persistent filling of the dome (RROC 3) in 1/14 cases (7%). An in-stent
      thrombus formation in one case (7%) was medically resolved without neurological
      deficit. Follow-up was available in 9/14 cases (64%) after a mean of 137 days (SD
      +/- 50). All followed cases depicted a complete occlusion (RROC1). CONCLUSIONS:
      The Acclino microstent showed a satisfactory safety profile and a promising rate
      of immediate and mid-term complete aneurysm occlusion for stent-assisted coil
      embolization in wide-neck intracranial aneurysms, warranting further
      investigation of the device.

PMID- 26301026
TI  - Exercise Induced Transient Neurological Deficit in a Patient with Cerebellar
      Developmental Venous Anomaly.
AB  - BACKGROUND: The association of venous angiomas or developmental venous anomalies
      (DVA) with transient neurological deficit is rare. We present a rare case of a
      cerebellar developmental venous anomaly resulting in transient neurological
      deficits. CASE DESCRIPTION: A 58-year-old man with recurrent left sided facial
      dysesthesia, hemiparesis, and mild difficulty ambulating after exercise. A
      similar episode was experienced six months earlier under the same circumstances.
      Computed tomographic (CT) scan demonstrated an ill-defined hyperdensity in the
      right cerebellar hemisphere. Cerebral angiography demonstrated a venous angioma
      that dilated with valsalva maneuver. CONCLUSION: We report the first case of a
      cerebellar venous angioma causing exercise induced transient neurologically
      deficits. Limiting strenuous exercise may be needed to avoid symptom recurrence.
      Further research is warranted on the hemodynamic effects of intracranial DVA's.

PMID- 26301027
TI  - Anomalous Right Vertebral Artery Originating from the Aortic Arch Distal to the
      Left Subclavian Artery: A Case Report and Review of the Literature.
AB  - OBJECTIVE: Present a case report of an anomalous origin of the right vertebral
      artery originating from the aortic arch distal to the left subclavian along with
      a review of cases reported to date in the literature. METHODS: Provide background
      information on this rare anomaly, present the case report, review the literature
      using PubMed, summarize previously reported cases to date, and discuss the
      underlying embryologic development of this anomaly along with its significance.
      RESULTS: We report a 54-year-old man presenting with a subarachnoid hemorrhage
      referred for diagnostic cerebral arteriography who was found to have an anomalous
      origin of the right vertebral artery originating from the aortic arch distal to
      the left subclavian artery in conjunction with a bovine arch. We also report 13
      previously reported cases along with their other associated variant anatomy.
      CONCLUSIONS: Based upon our present case and previously documented cases to date,
      this anomaly is a rare finding. An understanding of aberrant anatomy and its
      embryologic basis is paramount to avoiding inadvertent vascular injury during
      diagnostic cerebral angiography. Therefore, this abnormality must be considered
      if selective vertebral artery catheterization is difficult or unsuccessful.

PMID- 26301025
TI  - Rare Etiology of Bow Hunter's Syndrome and Systematic Review of Literature.
AB  - BACKGROUND: Bow Hunter's Syndrome is a mechanical occlusion of the vertebral
      artery which leads to a reduction in blood flow in posterior cerebral circulation
      resulting in transient reversible symptomatic vertebrobasilar insufficiency. CASE
      DESCRIPTION: We present a case of Bow Hunter's syndrome in a 53-year-old male
      that occurred after the patient underwent surgical correction of a proximal left
      subclavian artery aneurysm. Shortly after the surgery, the patient began to
      complain of transient visual changes, presyncopal spells, and dizziness upon
      turning his head to the left. A transcranial doppler ultrasound confirmed the
      diagnosis of Bow Hunter's syndrome. SYSTEMIC REVIEW: We analyzed the data on 153
      patients with Bow Hunter's syndrome from the literature. An osteophyte was the
      most common cause of vertebral artery occlusion, and left vertebral artery was
      more commonly involved in patients with Bow Hunter's syndrome. Dynamic
      angiography was the definitive imaging modality to confirm the diagnosis, and
      surgery was most successful in alleviating symptoms. CONCLUSION: We believe that
      this is the first case of iatrogenic Bow Hunter's syndrome after surgical
      intervention for an aneurysm repair, and the largest review of literature of Bow
      Hunter's syndrome. Dynamic angiography is the gold standard for the diagnosis of
      Bow Hunter's syndrome. Surgery should be considered as the primary treatment
      approach in these patients, especially those who have bony compression as the
      etiology.

PMID- 26301028
TI  - Using the Barrel Technique with the LVIS Jr (Low-profile Visualized Intraluminal
      Support) Stent to Treat a Wide Neck MCA Bifurcation Aneurysm.
AB  - The treatment of wide-neck bifurcation cerebral aneurysms is challenging
      especially if at least one of the arteries arise from an obtuse angle. These wide
      neck bifurcation aneurysms are difficult to treat with the usual balloon and
      stent assisted coiling, including Y stenting or double-barrel stent techniques
      [1, 2]. Other available options include using current devices with the waffle
      cone or double waffle cone techniques [3, 4]. Novel devices that are in
      development include intrasaccular devices and the barrel bifurcation vascular
      reconstruction device (Covidien) [5, 6, 7]. We report the use of a novel barrel
      technique using the LVIS (low-profile visualized intraluminal support) Jr stent
      for the treatment of a wide-neck bifurcation aneurysm. 

PMID- 26301029
TI  - Neurological Changes with Abnormal Brain Reactivity Following Coiling of Cerebral
      Aneurysm. Possible Reactivity to Endovascular Devices and Material?

PMID- 26301030
TI  - Occurrence and Management Strategies for Catheter Entrapment with Onyx Liquid
      Embolization.
AB  - In June 2012, Food and Drug Administration (FDA) issued a warning about the risk
      of catheter entrapment associated with Onyx embolization. We used our experience,
      literature review, and FDA Manufacturer and User Facility Device Experience
      (MAUDE) data review to identify five strategies to address catheter entrapment:
      1/. Surgical resection of vessel at point of entrapment of catheter and
      retraction from exterior portion at the femoral region; 2/. Advancing and closing
      the loop of snare over the entrapped catheter followed by retraction; 3/.
      Advancing the distal access catheter over the entrapped catheter and retraction
      with forward movement of the distal access catheters; 4/. Inflation of balloon
      catheter coaxial to the entrapped catheter with subsequent retraction; and 5/.
      Intravascular retention and internalization of microcatheter. In the MAUDE data,
      there were 77 reports of catheter entrapment with Onyx embolization;
      microcatheter was retracted by surgical excision in 15, endovascular snare or
      other retriever devices in 5, deliberately entrapped inside the vessel using
      stent in 1, and left without intervention within intravascular compartment in 27
      patients. 

PMID- 26301031
TI  - Hematoma Enlargement Among Patients with Traumatic Brain Injury: Analysis of a
      Prospective Multicenter Clinical Trial.
AB  - Observational studies suggest that hematomas continue to enlarge during
      hospitalization in patients with traumatic brain injury (TBI). There is limited
      data regarding factors associated with hematoma enlargement and on whether
      hematoma enlargement contributes directly to death and disability in patients
      with TBI. We analyzed data collected as part of the Resuscitation Outcomes
      Consortium Hypertonic Saline and TBI Study. Hematoma enlargement was ascertained
      and collected as a predefined safety endpoint. We evaluated the effect of
      hematoma enlargement on the risk of death and disability at 6 months based on the
      Extended Glasgow Outcome Scale (GOSE) (dichotomized as >4 or <=4) using stepwise
      logistic regression analysis. We adjusted for age (continuous variable),
      admission GCS score (dichotomized at >5 and <=5), and computed tomography (CT)
      scan classification (Marshall grades entered as a categorical variable). Of the
      1200 patients with severe TBI analyzed, 238 (19.8%) patients were reported to
      have hematoma enlargement as an adverse event. The proportion of patients who
      reached favorable outcome at 6 months was significantly lower (defined by GOSE of
      >4) among patients with hematoma enlargement (29.0% vs. 40.1%, p<.0001). The
      proportion of patients who died within 6 months was significantly higher among
      patients with hematoma enlargement (31.9% vs. 20.7%, p<.0001). After adjusting
      for age, admission GCS score, and initial injury score, the odds of favorable
      outcome was lower in patients with hematoma enlargement (odds ratio 0.7, 95%
      confidence interval [CI]; 0.5-0.97). Our results suggest that hematoma
      enlargement may be a direct contributor to death and disability in patients with
      TBI at 6 months. Future clinical trials must continue to evaluate new therapeutic
      interventions aimed at reducing hematoma enlargement with a favorable risk
      benefit ratio in patients with TBI. 

PMID- 26301032
TI  - Hyperacute Carotid Stent Thrombosis During Emergent Revascularization Treated
      with Intraarterial Eptifibatide After Systemic Administration of Recombinant
      Tissue Plasminogen Activator.
AB  - A 57-year-old woman with National Institutes of Health Stroke Scale (NIHSS) score
      of 26 was found to have an acute left carotid occlusion with tandem left M1
      thrombus within 1.5 hours of symptom onset. After no neurologic improvement
      following standard-dose intravenous (IV) recombinant tissue plasminogen activator
      (rtPA), emergent neuroendovascular revascularization with carotid stenting and
      intracranial thrombectomy were performed under conscious sedation. Thrombolysis
      in myocardial infarction (TIMI)-3 flow restoration and symptom resolution were
      achieved postprocedure; however, complete carotid stent thrombosis was noted on
      final angiographic runs (25 minutes later), correlating with neurologic decline.
      Rapid administration of an intraarterial (IA) bolus dose of eptifibatide resulted
      in TIMI-3 flow restoration, with neurologic improvement. The patient was
      discharged three days postrevascularization on dual antiplatelet therapy with an
      NIHSS score of 1. Intraarterial (IA) eptifibatide can be an effective option for
      acute stent occlusion during emergent neuroendovascular revascularization after
      IV rtPA administration. ABBREVIATIONS: CLEARCombined approach to lysis utilizing
      eptifibatide and RtPACTcomputed
      tomographicFrFrenchGPglycoproteinIAintraarterialICAinternal carotid
      arteryIVintravenousMCAmiddle cerebral arteryNIHSSNational Institutes of Health
      Stroke ScalertPArecombinant tissue plasminogen activatorTIMIthrombolysis in
      myocardial infarction.

PMID- 26301033
TI  - Human Immunodeficiency Viral Infection and Status Epilepticus in United States
      (2002-2009).
AB  - OBJECTIVE: To determine the association between human immunodeficiency virus
      (HIV) infection and status epilepticus and compare the outcomes of patients with
      status epilepticus with or without underlying HIV infection. METHODS: Patients
      with primary diagnosis of status epilepticus (cases) and status asthmaticus
      (controls) were identified from the 2002-2009 Nationwide Inpatient Sample (NIS)
      which is representative of all admissions in the United States. We performed
      logistic regression analysis adjusting for age, gender, co-morbid conditions,
      including hypertension, diabetes mellitus (DM), renal failure, alcohol use, and
      opportunistic infections. We compared the in hospital outcomes among patients
      admitted with status epilepticus in strata defined by underlying HIV infection.
      RESULTS: The rate of concurrent status epilepticus and HIV has increased over the
      last 7 years in hospitalized patients with status epilepticus in United States
      (0.14%-0.27% p<0.0001). The HIV infection was significantly associated with
      status epilepticus (odds ratio [OR]: 2.2; 95% confidence interval [CI]: 1.8-2.6;
      p<0.0001)) after adjusting for age, gender, opportunistic infections, and
      cardiovascular risk factors. The in-hospital mortality was significantly higher
      while discharge with none or minimal disability was significantly lower in status
      epilepticus patients with underlying HIV infection (17.5% vs. 9.9%, p<0.0001) and
      (50.4% vs. 63.3%, p<0.0001), respectively. CONCLUSIONS: Our study suggests that
      there is a direct association between HIV infection and status epilepticus. The
      proportion of patients admitted with concurrent status epilepticus and HIV
      infections is increasing and such patients have higher rates of poor discharge
      outcomes.

PMID- 26301034
TI  - Primary Stenting for Acute Ischemic Stroke Using the Enterprise Intracranial
      Stent: 2-Year Results of a Phase-I Trial.
AB  - BACKGROUND: The preliminary results of a prospective consecutive series of 20
      patients who underwent Enterprise-assisted recanalization for acute ischemic
      stroke were recently reported. Recanalization to thrombolysis in myocardial
      infarction (TIMI) grade 2 (n = 6) or 3 (n = 12) flow was achieved in 18 patients
      (90% revascularization rate). Good outcome (modified Rankin Scale [mRS] score of
      <=2) was obtained in 10 patients (50%) at 30 days. Here, we report the 2-year
      clinical follow-up data for patients enrolled in that prospective study. METHODS:
      Study patients were scheduled for examinations 2 years postprocedure at which
      time mRS and Barthel indices were obtained. RESULTS: Among 12 survivors at 2
      years, 11 of the 20 (55%) study patients improved to mRS score <=2 and 1 (5%)
      patient was disabled with an mRS 4. Of the 11 patients with mRS 0-2 scores, 10
      patients had a Barthel index of 100, and the 11th had a Barthel index of 95. One
      patient improved from mRS 3 to 2 during the interval between the 6- and 12-month
      postintervention evaluations after intervention. Eight of 13 (62%) survivors
      underwent follow-up imaging at 6 months without evidence of instent stenosis or
      thrombosis. CONCLUSION: At 2 years of follow-up, improvement in quality of life
      after acute stroke intervention was sustained; and 11 of 12 (92%) survivors had
      an excellent functional outcome. Improvement in functional status can occur even
      up to 1 year after stroke intervention. These results 2 years after acute stroke
      intervention demonstrate sustained benefit from acute intervention.
      ABBREVIATIONS: AISacute ischemic strokeCTcomputed tomographicFDAFood and Drug
      AdministrationIVintravenousMCAmiddle cerebral arterymRSmodified Rankin
      ScaleNIHSSNational Institutes of Health Stroke Scale ScoreSWIFTSolitaire FR With
      the Intention For Thrombectomy (SWIFT)TIMIthrombolysis in myocardial
      infarctiontPAtissue plasminogen activatorTREVOThrombectomy REvascularization of
      large Vessel Occlusions.

PMID- 26301035
TI  - Prevalence of and Factors Associated with Dural Thickness in Patients with Mild
      Cognitive Impairment and Alzheimer's Disease.
AB  - BACKGROUND AND PURPOSE: We performed this study to evaluate the prevalence of and
      factors associated with dural thickening in patients with mild cognitive
      impairment and Alzheimer's disease. METHODS: Alzheimer's disease neuroimaging
      initiative participants with axial FLAIR sequence magnetic resonance imaging
      (MRI) images were analyzed. Dural thickness was defined by a linear strip of
      hyperintense tissue signal along the dura mater observed in at least two
      different images without evidence of leptomeningeal involvement. RESULTS: Dural
      thickening was seen in 83 (34%) of 242 persons analyzed (mean age [+/-SD] 74+/-7
      years: 150 were men) with either mild cognitive impairment or Alzheimer's
      disease. The mini mental score was not different in persons with (26+/-0.3) and
      without (26+/-0.2) dural thickening (p = 0.6). The proportion of patients with
      moderate or severe cognitive impairment (defined by mini mental status score) was
      similar at baseline and at 12-month evaluations. The rates of annual progression
      according to Alzheimer's disease assessment scale (p = 0.06) and clinical
      dementia scale (p = 0.001) were higher in persons without dural thickening. The
      annual rate of volume loss in entorhinal cortex was higher among persons with
      dural thickening. CONCLUSIONS: We found relatively high prevalence of dural
      thickening in patients with mild cognitive impairment and Alzheimer's disease.

PMID- 26301037
TI  - Correction.
AB  - [This corrects the article on p. 37 in vol. 8, PMID: 26060529.]. 

PMID- 26301036
TI  - Validity of Laser Doppler Flowmetry in Predicting Outcome in Murine Intraluminal
      Middle Cerebral Artery Occlusion Stroke.
AB  - BACKGROUND: Laser Doppler flowmetry (LDF) can reliably reflect brain perfusion in
      experimental stroke by monitoring both the degree and the duration of relative
      regional cerebral blood flow (rCBF). Variation in rCBF was continuously monitored
      in 68 mice undergoing middle cerebral artery occlusion (MCAO) and 25 mice
      undergoing sham-operation and documented as LDF (%). Transcranial LDF changes in
      the territory of right middle cerebral artery during MCAO procedure were
      correlated with corrected infarct volume (CIV) and neurological deficit score
      (NDS). METHODS: Ninety-three C57BL/6 mice (Harlan Laboratories, Indianapolis, IN)
      between 9 and 11 weeks old were randomly selected and assigned to either MCAO for
      45 minutes (n = 68) or sham group (n = 25). Ischemia was induced using the
      transient intraluminal filament model of MCAO based on Koizumi's method and
      transcranial LDF was used to measure CBF during the procedure. Neurological
      deficits were measured at 2 and 23 hours after MCA reperfusion with NDS and 2%
      triphenyltetrazolium chloride (TTC) staining of carefully dissected brains was
      performed at 23 hours after reperfusion to determine infarct area. RESULTS: After
      common carotid artery occlusion (CCAO), there was a negative association between
      LDF drop from base line and NDS at 2 hours (r = -0.43, P = 0.038) and 23 hours (r
      = -0.61, P = 0.003). Also, a negative correlation was noted between MCA
      reperfusion LDF and NDS at 23 hours (r = -0.53, P = 0.001). Moreover, post-MCA
      reperfusion LDF had a positive association with initial CCAO LDF (r = 0.761, P =
      0.000) and MCA occlusion LDF (r = 0.31, P = 0.036) in predicting neurological
      outcome. NDS at 23 hours corresponded well with the infarct volume (r = 0.31, P =
      0.005). CONCLUSIONS: Greater augmentation of rCBF after MCA reperfusion was
      associated with improved neurological deficit scoring. Interestingly, greater
      reduction of regional cerebral blood flow after CCAO was also associated with
      improved neurological outcomes. The favorable neurological outcome is possibly
      due to interplay of factors such as vascular reserve, collaterals, and
      autoregulation mechanisms. We propose LDF changes as an additional noninvasive
      prognosticator of stroke outcome in the setting of experimental brain ischemia.

PMID- 26301038
TI  - Cardiovascular Imaging for the Primary Prevention of Atherosclerotic
      Cardiovascular Disease Events.
AB  - Traditional cardiovascular risk factors have well-known limitations for the
      accurate assessment of individual cardiovascular risk. Unlike risk factor-based
      scores which rely on probabilistic calculations derived from population-based
      studies, coronary artery calcium (CAC) scoring, and carotid ultrasound allow for
      the direct visualization and quantification of subclinical atherosclerosis with
      the potential for a more accurate, personalized risk assessment and treatment
      approach. Among strategies used to guide preventive management, CAC scoring has
      consistently and convincingly outperformed traditional risk factors for the
      prediction of adverse cardiovascular events. Moreover, several studies have
      demonstrated the potential of CAC testing to improve precision for the use of
      more intensive pharmacologic therapies, such as aspirin and statins, in patients
      most likely to derive benefit, as compared to atherosclerotic cardiovascular
      disease risk calculators. By comparison to CAC, the role of carotid ultrasound
      for the measurement of carotid intima-media thickness (CIMT) remains less well
      elucidated but may be significantly improved with the inclusion of plaque
      screening and novel three-dimensional measurements of plaque volume and
      morphology. Despite significant evidence supporting the ability of non-invasive
      atherosclerosis imaging (particularly CAC) to guide preventive management,
      imaging remains an under-utilized strategy among current guidelines and clinical
      practice. Herein, we review evidence regarding CAC and carotid ultrasound for
      patient risk classification, with a comparison of these techniques to currently
      advocated traditional risk factor-based scores.

PMID- 26301039
TI  - Brain-Specific Superoxide Dismutase 2 Deficiency Causes Perinatal Death with
      Spongiform Encephalopathy in Mice.
AB  - Oxidative stress is believed to greatly contribute to the pathogenesis of various
      diseases, including neurodegeneration. Impairment of mitochondrial energy
      production and increased mitochondrial oxidative damage are considered early
      pathological events that lead to neurodegeneration. Manganese superoxide
      dismutase (Mn-SOD, SOD2) is a mitochondrial antioxidant enzyme that converts
      toxic superoxide to hydrogen peroxide. To investigate the pathological role of
      mitochondrial oxidative stress in the central nervous system, we generated brain
      specific SOD2-deficient mice (B-Sod2(-/-)) using nestin-Cre-loxp system. B-Sod2(
      /-) showed perinatal death, along with severe growth retardation. Interestingly,
      these mice exhibited spongiform neurodegeneration in motor cortex, hippocampus,
      and brainstem, accompanied by gliosis. In addition, the mutant mice had markedly
      decreased mitochondrial complex II activity, but not complex I or IV, in the
      brain based on enzyme histochemistry. Furthermore, brain lipid peroxidation was
      significantly increased in the B-Sod2(-/-), without any compensatory alterations
      of the activities of other antioxidative enzymes, such as catalase or glutathione
      peroxidase. These results suggest that SOD2 protects the neural system from
      oxidative stress in the perinatal stage and is essential for infant survival and
      central neural function in mice.

PMID- 26301040
TI  - Epicatechin Reduces Striatal MPP+-Induced Damage in Rats through Slight Increases
      in SOD-Cu,Zn Activity.
AB  - Parkinson's disease is a neurodegenerative disorder characterized by movement
      alterations caused by reduced dopaminergic neurotransmission in the nigrostriatal
      pathway, presumably by oxidative stress (OS). MPP(+) intrastriatal injection
      leads to the overproduction of free radicals (FR). The increasing formation of FR
      produces OS, a decline in dopamine (DA) content, and behavioral disorders.
      Epicatechin (EC) has shown the ability to be FR scavenger, an antioxidant enzyme
      inductor, a redox state modulator, and transition metal chelator. Acute
      administration of 100 mg/kg of EC significantly prevented (P < 0.05) the circling
      MPP(+)-induced behavior (10 MUg/8 MUL). Likewise, EC significantly (P < 0.05)
      reduced the formation of fluorescent lipid products caused by MPP(+). MPP(+)
      injection produced (P < 0.05) increased enzymatic activity of the constitutive
      nitric oxide synthase (cNOS). This effect was blocked with acute EC pretreatment.
      Cu/Zn-dependent superoxide dismutase (Cu/Zn-SOD) activity was significantly (P <
      0.05) reduced as a consequence of MPP(+) damage. EC produced a slight increase
      (~20%) in Cu/Zn-SOD activity in the control group. Such effects persisted in
      animals injured with MPP(+). The results show that EC is effective against MPP(+)
      induced biochemical and behavioral damage, which is possible by an increase in
      Cu/Zn-SOD activity. 

PMID- 26301041
TI  - Redox Status and Aging Link in Neurodegenerative Diseases 2015.

PMID- 26301043
TI  - The Role of Oxidative Damage in the Pathogenesis and Progression of Alzheimer's
      Disease and Vascular Dementia.
AB  - Oxidative stress (OS) has been demonstrated to be involved in the pathogenesis of
      the two major types of dementia: Alzheimer's disease (AD) and vascular dementia
      (VaD). Evidence of OS and OS-related damage in AD is largely reported in the
      literature. Moreover, OS is not only linked to VaD, but also to all its risk
      factors. Several researches have been conducted in order to investigate whether
      antioxidant therapy exerts a role in the prevention and treatment of AD and VaD.
      Another research field is that pertaining to the heat shock proteins (Hsps), that
      has provided promising findings. However, the role of OS antioxidant defence
      system and more generally stress responses is very complex. Hence, research on
      this topic should be improved in order to reach further knowledge and discover
      new therapeutic strategies to face a disorder with such a high burden which is
      dementia. 

PMID- 26301044
TI  - Dietary Tocotrienol/gamma-Cyclodextrin Complex Increases Mitochondrial Membrane
      Potential and ATP Concentrations in the Brains of Aged Mice.
AB  - Brain aging is accompanied by a decrease in mitochondrial function. In vitro
      studies suggest that tocotrienols, including gamma- and delta-tocotrienol (T3),
      may exhibit neuroprotective properties. However, little is known about the effect
      of dietary T3 on mitochondrial function in vivo. In this study, we monitored the
      effect of a dietary T3/gamma-cyclodextrin complex (T3CD) on mitochondrial
      membrane potential and ATP levels in the brain of 21-month-old mice. Mice were
      fed either a control diet or a diet enriched with T3CD providing 100 mg T3 per kg
      diet for 6 months. Dietary T3CD significantly increased mitochondrial membrane
      potential and ATP levels compared to those of controls. The increase in MMP and
      ATP due to dietary T3CD was accompanied by an increase in the protein levels of
      the mitochondrial transcription factor A (TFAM). Furthermore, dietary T3CD
      slightly increased the mRNA levels of superoxide dismutase, gamma-glutamyl
      cysteinyl synthetase, and heme oxygenase 1 in the brain. Overall, the present
      data suggest that T3CD increases TFAM, mitochondrial membrane potential, and ATP
      synthesis in the brains of aged mice.

PMID- 26301042
TI  - Electron Transport Disturbances and Neurodegeneration: From Albert Szent
      Gyorgyi's Concept (Szeged) till Novel Approaches to Boost Mitochondrial
      Bioenergetics.
AB  - Impaired function of certain mitochondrial respiratory complexes has long been
      linked to the pathogenesis of chronic neurodegenerative disorders such as
      Parkinson's and Huntington's diseases. Furthermore, genetic alterations of
      mitochondrial genome or nuclear genes encoding proteins playing essential roles
      in maintaining proper mitochondrial function can lead to the development of
      severe systemic diseases associated with neurodegeneration and vacuolar
      myelinopathy. At present, all of these diseases lack effective disease modifying
      therapy. Following a brief commemoration of Professor Albert Szent-Gyorgyi, a
      Nobel Prize laureate who pioneered in the field of cellular respiration,
      antioxidant processes, and the roles of free radicals in health and disease, the
      present paper overviews the current knowledge on the involvement of mitochondrial
      dysfunction in central nervous system diseases associated with neurodegeneration
      including Parkinson's and Huntington's disease as well as mitochondrial
      encephalopathies. The review puts special focus on the involvement and the
      potential therapeutic relevance of peroxisome proliferator-activated receptor
      gamma coactivator 1-alpha (PGC-1alpha), a nuclear-encoded master regulator of
      mitochondrial biogenesis and antioxidant responses in these disorders, the
      transcriptional activation of which may hold novel therapeutic value as a more
      system-based approach aiming to restore mitochondrial functions in
      neurodegenerative processes. 

PMID- 26301045
TI  - Polydatin Alleviates Small Intestine Injury during Hemorrhagic Shock as a SIRT1
      Activator.
AB  - OBJECTIVE: To evaluate the role of SIRT1 in small intestine damage following
      severe hemorrhagic shock and to investigate whether polydatin (PD) can activate
      SIRT1 in shock treatment. RESEARCH DESIGN AND METHODS: The severe hemorrhagic
      shock model was reproduced in Sprague Dawley rats. MAIN OUTCOME MEASURES: Two
      hours after drug administration, half of the rats were assessed for survival time
      evaluation and the remainder were used for small intestinal tissue sample
      collection. RESULTS: Bleeding and swelling appeared in the small intestine with
      epithelial apoptosis and gut barrier disturbance during hemorrhagic shock. SIRT1
      activity and PGC-1alpha protein expression of the small intestine were decreased,
      which led to an increase in acetylated SOD2 and decreases in the expression and
      activity of SOD2, resulting in severe oxidative stress. The decreased SIRT1
      activity and expression were partially restored in the PD administration group,
      which showed reduced intestine injury and longer survival time. Notably, the
      effect of PD was abolished after the addition of Ex527, a selective inhibitor of
      SIRT1. CONCLUSIONS: The results collectively suggest a role for the SIRT1-PGC
      1alpha-SOD2 axis in small intestine injury following severe hemorrhagic shock and
      that PD is an effective SIRT1 activator for the shock treatment.

PMID- 26301046
TI  - Perceptions of Patients and Families who Received a Music Intervention During
      Mechanical Ventilation.
AB  - The intensive care unit (ICU) is a technologically-driven environment where
      critically ill patients and their families have significant physical and
      emotional experiences. Mechanically ventilated (MV) patients can experience
      significant distress from anxiety and pain. Music listening is one integrative
      intervention that has been shown to reduce anxiety as well as other symptoms that
      contribute to distress in MV patients. This is a report of MV patient and family
      experiences from a larger research study whose aim was to evaluate levels of
      anxiety and sedative exposure with use of a patient-directed music intervention.
      Understanding perceptions of MV patients and families regarding the effectiveness
      of music listening will guide improvement of their care.

PMID- 26301047
TI  - Second line systemic therapies for hepatocellular carcinoma: Reasons for the
      failure.
AB  - Hepatocellular carcinoma (HCC) is the main cause of death in patients with
      cirrhosis, with an increasing incidence worldwide. Sorafenib is the choice
      therapy for advanced HCC. Over time several randomized phase III trials have been
      performed testing sunitinib, brivanib, linifanib and other molecules in head-to
      head comparison with Sorafenib as first-line treatment for advanced-stage HCC,
      but none of these has so far been registered in this setting. Moreover, another
      feared vacuum arises from the absence of molecules registered as second-line
      therapy for patients who have failed Sorafenib, representing an urgent unmet
      medical need. To date all molecules tested as second-line therapies for advanced
      hepatocellular carcinoma, failed to demonstrate an increased survival compared to
      placebo. What are the possible reasons for the failure? What we should expect in
      the near future? 

PMID- 26301049
TI  - Prediction of liver cirrhosis, using diagnostic imaging tools.
AB  - Early diagnosis of liver cirrhosis is important. Ultrasound-guided liver biopsy
      is the gold standard for diagnosis of liver cirrhosis. However, its invasiveness
      and sampling bias limit the applicability of the method. Basic imaging for the
      diagnosis of liver cirrhosis has developed over the last few decades, enabling
      early detection of morphological changes of the liver by ultrasonography (US),
      computed tomography, and magnetic resonance imaging (MRI). They are also accurate
      diagnostic methods for advanced liver cirrhosis, for which early diagnosis is
      difficult. There are a number of ways to compensate for this difficulty,
      including texture analysis to more closely identify the homogeneity of hepatic
      parenchyma, elastography to measure the stiffness and elasticity of the liver,
      and perfusion studies to determine the blood flow volume, transit time, and
      velocity. Amongst these methods, elastography using US and MRI was found to be
      slightly easier, faster, and able to provide an accurate diagnosis. Early
      diagnosis of liver cirrhosis using MRI or US elastography is therefore a
      realistic alternative, but further research is still needed. 

PMID- 26301048
TI  - Intestinal barrier dysfunction in cirrhosis: Current concepts in pathophysiology
      and clinical implications.
AB  - The intestinal lumen is a host place for a wide range of microbiota and sets a
      unique interplay between local immune system, inflammatory cells and intestinal
      epithelium, forming a physical barrier against microbial invaders and toxins.
      Bacterial translocation is the migration of viable or nonviable microorganisms or
      their pathogen-associated molecular patterns, such as lipopolysaccharide, from
      the gut lumen to the mesenteric lymph nodes, systemic circulation and other
      normally sterile extraintestinal sites. A series of studies have shown that
      translocation of bacteria and their products across the intestinal barrier is a
      commonplace in patients with liver disease. The deterioration of intestinal
      barrier integrity and the consulting increased intestinal permeability in
      cirrhotic patients play a pivotal pathophysiological role in the development of
      severe complications as high rate of infections, spontaneous bacterial
      peritonitis, hepatic encephalopathy, hepatorenal syndrome, variceal bleeding,
      progression of liver injury and hepatocellular carcinoma. Nevertheless, the exact
      cellular and molecular mechanisms implicated in the phenomenon of microbial
      translocation in liver cirrhosis have not been fully elucidated yet. 

PMID- 26301050
TI  - Immunology of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is primarily a malignancy of the liver, advancing
      from a damaged, cirrhotic liver to HCC. Globally, HCC is the sixth most prevalent
      cancer and the third-most prevalent reason for neoplastic disease-related deaths.
      A diverse array of infiltrating immunocytes regulates the development and
      progression of HCC, as is the case in many other cancers. An understanding of the
      various immune components during HCC becomes necessary so that novel therapeutic
      strategies can be designed to combat the disease. A dysregulated immune system
      (including changes in the number and/or function of immune cells, cytokine
      levels, and the expression of inhibitory receptors or their ligands) plays a key
      role in the development of HCC. Alterations in either the innate or adaptive arm
      of the immune system and cross-talk between them make the immune system tolerant
      to tumors, leading to disease progression. In this review, we have discussed the
      status and roles of various immune effector cells (e.g., dendritic cells, natural
      killer cells, macrophages, and T cells), their cytokine profile, and the
      chemokine-receptor axis in promoting or impeding HCC. 

PMID- 26301051
TI  - Addiction specialist's role in liver transplantation procedures for alcoholic
      liver disease.
AB  - Although liver transplantation (LT) is performed increasingly for patients with
      end-stage alcoholic liver disease (ALD), the topic remains controversial.
      Traditionally, the role of an addiction specialist focused on the screening and
      identification of patients with a high risk on relapse in heavy alcohol use.
      These patients were in many cases subsequently excluded from a further LT
      procedure. Recently, awareness is growing that not only screening of patients but
      also offering treatment, helping patients regain and maintain abstinence is
      essential, opening up a broader role for the addiction specialist (team) within
      the whole of the transplant procedure. Within this context, high-risk assessment
      is proposed to be an indication of increasing addiction treatment intensity,
      instead of being an exclusion criterion. In this review we present an overview
      regarding the state of the art on alcohol relapse assessment and treatment in
      patients with alcohol use disorders, both with and without ALD. Screening,
      treatment and monitoring is suggested as central roles for the addiction
      specialist (team) integrated within transplant centers. 

PMID- 26301052
TI  - New treatment strategies for hepatitis C infection.
AB  - Hepatitis C infection can lead to cirrhosis and hepatocellular carcinoma and it
      is an important cause of mortality and morbidity. Achieving a sustained
      virological response has been the major aim for decades. Interferon treatment was
      the primarily developed therapy against the infection. Addition of the guanosine
      analog ribavirin to stop viral RNA synthesis increased the response rates as well
      as the adverse effects of the treatment. The increasing demands for alternative
      regimens led to the development of direct-acting antivirals (DAAs). The approval
      of sofosbuvir and simeprevir signaled a new era of antiviral treatment for
      hepatitis C infection. Although the majority of studies have been performed with
      DAAs in combination with interferon and resulted in a decrease in treatment
      duration and increase in response rates, the response rates achieved with
      interferon-free regimens provided hope for patients ineligible for therapy with
      interferon. Most DAA studies are in phase II leading to phase III. In the near
      future more DAAs are expected to be approved. The main disadvantage of the
      therapy remains the cost of the drugs. Here, we focus on new treatment strategies
      for hepatitis C infection as well as agents targeting hepatitis C virus
      replication that are in clinical development. 

PMID- 26301053
TI  - Recent advances in mouse models of obesity- and nonalcoholic steatohepatitis
      associated hepatocarcinogenesis.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common cancer, and obesity has
      been established as a risk factor for HCC development. Nonalcoholic
      steatohepatitis (NASH) is apparently the key link between obesity and
      hepatocarcinogenesis, and obesity also accelerates HCC development
      synergistically with other risk factors, such as hepatitis virus infection and
      alcohol consumption. As an explanation for the pathogenesis of NASH, the so
      called "two-hit" theory has been widely accepted, but recently, a better model,
      the so-called "multiple-hits hypothesis" was proposed, which states that many
      disease-promoting factors may occur in parallel, rather than consecutively.
      However, the overall mechanism remains largely unknown. Various cell-cell and
      organ-organ interactions are involved in the pathogenesis of NASH, and thus
      appropriate in vivo disease models are essential for a deeper understanding.
      However, replicating the full spectrum of human NASH has been difficult, as NASH
      involves obesity, insulin resistance, steatohepatitis, fibrosis, and ultimately
      HCC, and the lack of an appropriate mouse model has been a considerable barrier
      to determining the missing links among obesity, NASH, and HCC. In recent years,
      several innovative mouse models presenting obesity- and NASH-associated HCC have
      been established by modified diets, chemotoxic agents, genetic manipulation, or a
      combination of these factors, shedding some light on this complex network and
      providing new therapeutic strategies. Thus, in this paper, I review the mouse
      models of obesity- and NASH-associated HCC, especially focusing on recent
      advances and their clinical relevance. 

PMID- 26301054
TI  - Model for end-stage liver disease-Na score or Maddrey discrimination function
      index, which score is best?
AB  - AIM: To compare the ability of model for end-stage liver disease (MELD)-Na and
      Maddrey discrimination function index (DFI) to predict mortality at 30 and 90 d
      in patients with alcoholic hepatitis (AH). METHODS: We prospectively assessed 52
      patients with AH. Demographic, clinical and laboratory parameters were obtained.
      MELD-Na and Maddrey DFI were calculated on admission. Short-term mortality was
      assessed at 30 and 90 d. Receiver operating characteristic curve analysis was
      performed. RESULTS: Thirty-day and 90-d mortality was 44% and 58%, respectively.
      In the univariate analysis, sodium levels was associated with mortality at 30 and
      90 d (P = 0.001 and P = 0.03). Child stage, encephalopathy, ascites, or types of
      treatment were not associated with mortality. MELD-Na was the only predictive
      factor for mortality at 90 d. For 30-d mortality area under the curve (AUC) was
      0.763 (95%CI: 0.63-0.89) for Maddrey DFI and 0.784 for MELD-Na (95%CI: 0.65-0.91,
      P = 0.82). For 90-d mortality AUC was 0.685 (95%CI: 0.54-0.83) for Maddrey DFI
      and 0.8710 for MELD-Na (95%CI: 0.76-0.97, P = 0.041). CONCLUSION: AH is
      associated with high short-term mortality. Our results show that MELD-Na is a
      more valuable model than DFI to predict short-term mortality.

PMID- 26301055
TI  - Multidrug-Resistant Proteus mirabilis Isolated From Newly Weaned Infant Rhesus
      Monkeys and Ferrets.
AB  - BACKGROUND: Proteus mirabilis is an important uropathogen that causes complicated
      Urinary Tract Infection (UTI) and induces diarrhea in infants. OBJECTIVES: This
      study aimed to investigate P. mirabilis infection in newly weaned infant rhesus
      monkeys (Macaca mulatta) and ferrets (Mustela putorius furo) with diarrhea.
      MATERIALS AND METHODS: Stool samples were collected from 74 rhesus monkeys and 12
      ferrets with diarrhea. Proteus mirabilis was isolated from the samples through
      Polymerase Chain Reaction. The isolated P. mirabilis was subjected to
      antimicrobial susceptibility tests. RESULTS: Seven (7/74, 9.5%) and four (4/12,
      30%) P. mirabilis strains were detected in the stool samples collected from the
      monkeys and ferrets, respectively. Sequence analyses showed that the isolated P.
      mirabilis was closely related to P. mirabilis strain HI4320, which was isolated
      from the urine of a patient with a long-term indwelling urinary catheter. In
      addition, the isolates demonstrated multidrug resistance. CONCLUSIONS: Rhesus
      monkeys and ferrets are susceptible to P. mirabilis, making them useful as animal
      models for future studies on the mechanism of P. mirabilis-induced UTI and its
      corresponding treatment.

PMID- 26301056
TI  - Role of Oxidative Stress Response and Trehalose Accumulation in the Longevity of
      Fission Yeast.
AB  - BACKGROUND: Glucose is the preferred carbon and energy source in most organisms
      and plays an active role in the regulation of many biological processes. However,
      an excess of glucose leads to such undesirable conditions as diabetes and age
      related diseases. Since Schizosaccharomyces pombe homologous of many human genes,
      it offers several advantages for the investigation of the molecular mechanisms
      underlying human disease and aging studies. We have identified two glucose
      repression-resistant mutants (ird5 and ird11) of S. pombe. OBJECTIVES: We aimed
      to investigate the possible relationship between lifespan extension and oxidative
      stress response induced by exposure to hydrogen peroxide alongside the trehalose
      accumulation level by using the two S. pombe mutants (i.e. ird5 and ird11), which
      are repressed by glucose and are resistant to oxidative stress. MATERIALS AND
      METHODS: We employed trehalose accumulation measurement and colony-forming unit
      (CFU) counting using the ird mutants in exponential and stationary phases and
      compared them to the wild type grown in repressed, de-repressed, and stressed
      conditions to clarify the possible relationship between glucose signaling,
      oxidative stress response, and lifespan in S. pombe. RESULTS: The lifespan of the
      ird5 mutant was significantly longer that of either the ird11 mutant or the wild
      type cells. Under repressed condition, the trehalose content was increased
      remarkably on the 3rd day of the study in the ird11 mutant and the wild type.
      Under de-repressed condition, the level of intracellular trehalose was notably
      increased on the 3rd day in ird11. Under stressed condition, the trehalose level
      in ird11 was increased on the 3rd day as a pattern similar to that observed in
      the wild type. CONCLUSIONS: Our results demonstrated no significant correlation
      between the ird5 lifespan and the trehalose concentration. Likewise, the
      correlation between lifespan extension, trehalose accumulation, and cellular
      resistance to hydrogen peroxide was not significant.

PMID- 26301057
TI  - Prevalence of Human T-Lymphotropic Virus Types I and II in Patients With
      Hematological Disorders in Isfahan, Iran.
AB  - BACKGROUND: Human T-cell lymphotropic virus types Iota and IotaIota (HTLV-Iota
      and HTLV-II) are deltaretroviruses which may cause leukemia, lymphoma and HTLV
      associated myelopathy/tropical spastic paraparesis (HAM/TSP). In addition, HTLV-1
      may be related to thalassemia and hemophilia cases after blood transfusion.
      OBJECTIVES: The aim of this study was evaluation of the prevalence of HTLVs in
      patients with hematological disorders (leukemia, thalassemia, lymphoma and
      hemophilia). PATIENTS AND METHODS: This cross-sectional study was conducted
      during April to October 2012. A total of 101 serum samples were collected from
      patients and were stored at -20oC. DNA was extracted from serum by an extraction
      kit. The extracted DNA was tested by polymerase chain reaction (PCR) for
      detection of HTLV-Iota and HTLV-II pol and tax gene sequences, respectively.
      Samples were collected from 67 (66.33%), 20 (19.80%), 4 (3.96%), and 10 (9.90%)
      patients with thalassemia, leukemia, lymphoma and hemophilia, respectively.
      RESULTS: One thalassemia sample was HTLV-Iota positive, but none of the samples
      contained the genome of HTLV-II. The prevalence of HTLV-Iota in this study in
      patients with hematological disorders was 0.99%. CONCLUSIONS: The prevalence of
      HTLV-Iota in hematological disorders was similar to that of other parts of Iran.
      The present study revealed that HTLV-Iota screening should be performed before
      blood transfusion to reduce the risk of virus transmission in patients with
      hematological disorders. More study should be performed to detect these viruses
      in blood donors.

PMID- 26301058
TI  - Use of Restriction Fragment Length Polymorphism to Rapidly Identify Dermatophyte
      Species Related to Dermatophytosis.
AB  - BACKGROUND: Dermatophytes are a group of keratinophilic fungi worldwide, which
      can infect the skin, hair and nails of humans and animals. This genus includes
      several species that present different features of dermatophytosis. Although,
      laboratory diagnosis of dermatophytes is based on direct microscopy, biochemical
      tests and culture, these manners are expensive, time consuming and need skilled
      staff. Therefore, molecular methods like PCR-RFLP are the beneficial tools for
      identification, which are rapid and sensitive. Thus, dermatophyte species are
      able to generate characteristic band patterns on agarose gel electrophoresis
      using PCR-RFLP technique, which leads to successful identification at the species
      level within a 5-hour period. OBJECTIVES: The purpose of this study was to study
      inter- and intraspecific genomic variations for identification of clinically
      important dermatophyte species obtained from clinical specimens in Isfahan, Iran
      using PCR-RFLP. MATERIALS AND METHODS: From March 2011 to August 2012, 135
      clinical isolates were collected from infected patients at Isfahan, Iran. ITS1
      5.8S-ITS2 region of rDNA was amplified using universal fungal primers.
      Subsequently, amplified products were digested by the MvaI restriction enzyme.
      Using discriminating band profiles on agarose gel, dermatophyte species were
      identified. However, DNA sequencing was used for unidentifiable strains. RESULTS:
      The specimens were obtained from skin scrapings (70.3%), nail (24.4%) and hair
      (5.1%) clippings. Most patients were between 21 - 30 years and the ratio of male
      to female was 93/42. Trichophyton interdigitale was the commonest isolate (52.5%)
      in our findings, followed by Epidermophyton floccosum (24.4%), T. rubrum (16.2%),
      Microsporum canis (2.2%), T. erinacei (1.4%), T. violaceum (1.4%), T. tonsurans
      (0.7%) and M. gypseum (0.7%) based on PCR-RFLP. CONCLUSIONS: Combination of
      traditional methods and molecular techniques considerably improves identification
      of dermatophytes in the species level in clinical laboratories, which can lead to
      properly antifungal therapy and successful management of infections. However,
      restriction and specificity and sensitivity should be lowered and increased,
      respectively, to be useful for a wide variety of clinical applications.

PMID- 26301059
TI  - Pseudomonas aeruginosa PAO-1 Lipopolysaccharide-Diphtheria Toxoid Conjugate
      Vaccine: Preparation, Characterization and Immunogenicity.
AB  - BACKGROUND: Treatment of Pseudomonas aeruginosa PAO-1 infections through
      immunological means has been proved to be efficient and protective. OBJECTIVES:
      The purpose of this study was to produce a conjugate vaccine composed of
      detoxified lipopolysaccharide (D-LPS) P. aeruginosa and diphtheria toxoid (DT).
      MATERIALS AND METHODS: Firstly, LPS was purified and characterized from P.
      aeruginosa PAO1 and then detoxified. D-LPS was covalently coupled to DT as a
      carrier protein via amidation method with adipic acid dihydrazide (ADH) as a
      spacer molecule and 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide (EDAC) as a
      linker. The molar ratio of LPS to DT in the prepared conjugate was 3:1. The
      immunogenicity of D-LPS-DT conjugate vaccine in mice model was evaluated as well.
      RESULTS: The conjugate was devoid of endotoxin activity and 0.125 U/mL of D-LPS
      was acceptable for immunization. D-LPS-DT conjugate was nonpyrogenic for rabbits
      and nontoxic for mice. Mice immunization with D-LPS-DT conjugate vaccine elicited
      the fourfold higher IgG antibody compared to D-LPS. Anti-LPS IgG antibody was
      predominantly IgG1 subclass and then IgG3, IgG2a and IgG2b, respectively.
      CONCLUSIONS: Vaccine based on the conjugation of P. aeruginosa PAO-1 LPS with DT
      increased anti-LPS antibodies and had a significant potential to protect against
      Pseudomonas infections.

PMID- 26301060
TI  - Antagonistic Characteristics Against Food-borne Pathogenic Bacteria of Lactic
      Acid Bacteria and Bifidobacteria Isolated from Feces of Healthy Thai Infants.
AB  - BACKGROUND: Food-borne pathogens are among the most significant problems in
      maintaining the health of people. Many probiotics have been widely reported to
      alleviate and protect against gastrointestinal infections through antibacterial
      secretion. However, the majority of them cannot always play antagonistic roles
      under gut conditions. Probiotic bacteria of human origin must possess other
      protective mechanisms to survive, out-compete intestinal flora and to
      successfully establish in their new host at a significant level. OBJECTIVES:
      Probiotic characteristics of Lactic Acid Bacteria (LAB) and bifidobacteria
      isolated from the feces of Thai infants were primarily investigated in terms of
      gastric acid and bile resistances, antibacterial activity and mucin adhesion
      ability. Antagonistic interaction through secretion of antibacterial compounds
      and competitive exclusion against food-borne pathogens were also evaluated.
      MATERIALS AND METHODS: Culturable LAB and bifidobacteria were isolated from feces
      of Thai infants. Their ability to withstand gastric acid and bile were then
      evaluated. Acid and bile salt tolerant LAB and bifidobacteria were identified.
      They were then further assessed according to their antagonistic interactions
      through antibacterial secretion, mucin adhesion and competitive mucin adhesion
      against various food-borne pathogenic bacteria. RESULTS: Gastric acid and bile
      tolerant LAB and bifidobacteria isolated from healthy infant feces were
      identified and selected according to their antagonistic interaction against
      various food-borne pathogenic bacteria. These antagonistic probiotics included
      four strains of Lactobacillus rhamnosus, two strains of L. casei, five strains of
      L. plantarum, two strains of Bifidobacterium longum subsp. longum and three
      strains of B. bifidum. All strains of the selected LAB inhibited all pathogenic
      bacteria tested through antibacterial secretion, while bifidobacteria showed high
      level of competitive exclusion against the pathogenic bacteria. CONCLUSIONS:
      These human-derived LAB and bifidobacteria exhibited different mechanisms
      involved in pathogenic inhibition. Therefore a combination of these probiotic
      strains could be a great promise and possibility for the development of probiotic
      products to effectively prevent and control food-borne infection in humans.

PMID- 26301061
TI  - Molecular Characteristics of Nasal Carriage Methicillin-Resistant Coagulase
      Negative Staphylococci in School Students.
AB  - BACKGROUND: Coagulase-negative staphylococci (CoNS) are opportunistic pathogens.
      Methicillin resistance is common in CoNS and may play an important role as
      reservoir of staphylococcal cassette chromosome mec (SCCmec) for Staphylococcus
      aureus. OBJECTIVES: The aim of this study was to determine molecular
      characteristics of nasal carriage of methicillin-resistant coagulase negative
      staphylococci among students. MATERIALS AND METHODS: MR-CoNS from both nares of
      students were collected. Resistance to methicillin was determined by cefoxitin
      (30MUg) disk diffusion test. SCCmec typing was performed using multiplex PCR by
      mec complex classes and ccr genes. Antimicrobial susceptibility profiles were
      determined on Mueller-Hinton agar according to CLSI. RESULTS: A total of 600
      consecutive students were enrolled in this study; 430 of whom (71.7%) had CoNS.
      Seventy-two MR-CoNS strains, 21 (29.2%) S. lugdunensis, 17 (23.6%) S.
      haemolyticus, 17 (23.6%) S. saprophyticus, 9 (12.5%) S. epidermidis and 8 (11.1%)
      S. schleiferi were isolated. MR-CoNS rate in nasal carriage was 16.7%. All
      strains were susceptible to vancomycin. Forty-eight (66.7%) had a single SCCmec
      type including types I (n = 5), II (n = 4), III (n = 7), IV (n = 19) and V (n =
      13), whereas 5 (6.9%) had two types including III + IV (n = 2), III + V (n = 1)
      and IV + V (n = 2). Nineteen strains (26.4%) were non-typeable for their SCCmec
      and ccr. Types IV and V SCCmec were associated with S. lugdunensis and S.
      haemolyticus, respectively. CONCLUSIONS: SCCmec types IV and V were prevalent in
      MR-CoNS and few isolates could harbor more than one type.

PMID- 26301062
TI  - Tricyclic Analogues of Epidithiodioxopiperazine Alkaloids with Promising In Vitro
      and In Vivo Antitumor Activity.
AB  - Epipolythiodioxopiperazine (ETP) alkaloids are structurally elaborate alkaloids
      that show potent antitumor activity. However, their high toxicity and
      demonstrated interactions with various biological receptors compromises their
      therapeutic potential. In an effort to mitigate these disadvantages, a short
      stereocontrolled construction of tricyclic analogues of epidithiodioxopiperazine
      alkaloids was developed. Evaluation of a small library of such structures against
      two invasive cancer cell lines defined initial structure-activity relationships
      (SAR), which identified 1,4-dioxohexahydro-6H-3,8a-epidithiopyrrolo[1,2
      a]pyrazine 3c and related structures as particularly promising antitumor agents.
      ETP alkaloid analogue 3c exhibits low nanomolar activity against both solid and
      blood tumors in vitro. In addition, 3c significantly suppresses tumor growth in
      mouse xenograft models of melanoma and lung cancer, without obvious signs of
      toxicity, following either intraperitoneal (IP) or oral administration. The short
      synthesis of molecules in this series will enable future mechanistic and
      translational studies of these structurally novel and highly promising clinical
      antitumor candidates.

PMID- 26301063
TI  - Patient preference and tolerability of a DPP-4 inhibitor versus a GLP-1 analog in
      patients with type 2 diabetes mellitus inadequately controlled with metformin: a
      24-week, randomized, multicenter, crossover study.
AB  - OBJECTIVE: The present study aimed to assess the patient preference and
      tolerability of oral dipeptidyl peptidase-4 inhibitor (vildagliptin) versus
      injectable glucagon-like peptide-1 analog (liraglutide) in patients with type 2
      diabetes mellitus inadequately controlled with metformin monotherapy. METHODS:
      This 24-week, randomized, multicenter, crossover study, patients with type 2
      diabetes mellitus inadequately controlled on metformin monotherapy with
      hemoglobin A1c (HbA1c) ?6.5% and ?9.0% were randomized in a crossover manner to
      receive either vildagliptin/metformin single-pill combination (SPC) 50/1000 mg
      twice daily (n = 32) or 1.2 mg liraglutide as an add-on to metformin (0.6 mg
      [weeks 0-1] followed by 1.2 mg [weeks 2-12] once daily/1000 mg twice daily) (n =
      30) for the first 12 weeks. RESULTS: Patient preference at week 24 was similar,
      with 51.7% (n = 31) patients preferring vildagliptin/metformin SPC compared with
      48.3% (n = 29) preferring liraglutide as an add-on to metformin therapy (p =
      0.449). Post hoc analyses showed that more elderly patients (?65 years) preferred
      vildagliptin (65%; n = 13) over liraglutide (35%; n = 7) therapy. Liraglutide was
      associated with better improvement in fasting plasma glucose (-21.5 mg/dl versus 
      3.4 mg/dl) and HbA1c (-0.5% versus -0.3%) levels. Fewer adverse events were
      reported with vildagliptin/metformin SPC (n = 16) compared with liraglutide as
      add-on to metformin treatment (n = 46). CONCLUSIONS: In this pilot study,
      although both vildagliptin and liraglutide therapies were preferred similarly by
      the patients and showed effective control of glycemia over 12 weeks, vildagliptin
      was associated with fewer adverse events and was preferred more by elderly
      patients.

PMID- 26301064
TI  - The effects of intermittent vitamin D3 supplementation on muscle strength and
      metabolic parameters in postmenopausal women with type 2 diabetes: a randomized
      controlled study.
AB  - BACKGROUND: The aim of this study was to evaluate the effect of weekly vitamin D3
      supplementation on metabolic parameters and muscle strength of postmenopausal
      women with type 2 diabetes. METHODS: A total of 38 patients with serum 25-hydroxy
      vitamin D [25(OH)D] below 30 ng/ml and hand strength below 20 kg were randomly
      assigned to oral vitamin D3 (6600 IU/week in 2 cc oil preparation) or 2 cc olive
      oil weekly for 3 months. RESULTS: There were nonsignificant increases in serum
      25(OH)D in the intervention group to 22.98 +/- 4.23 ng/ml and nonsignificant
      decreases in the control group to 22.84 +/- 3.88 (26% of the intervention and 48%
      of the control groups had 25(OH)D < 20 ng/ml). Handgrip strength improved
      significantly in the intervention group (right arm 17.4 +/- 2.68 to 19.9 +/- 3.53
      kg, p = 0.002; left arm 16.31 +/- 2.6 to 18.46 +/- 3.2 kg, p < 0.001) but not in
      the control group (right arm 16.87 +/- 3.99 to 17.93 +/- 4.91 kg, p = 0.1; left
      arm 16.13 +/- 4.29 to 16.86 +/- 4.79 kg, p < 0.2). More patients in the control
      group became obese at the end of the study period (p = 0.014). There were no
      significant changes in mean fasting glucose, glycated haemoglobin (HbA1c), serum
      triglycerides and blood pressure with vitamin D supplementation. Systolic blood
      pressure increased significantly in the control group from 136.6 +/- 18.6 to
      141.4 +/- 17.6 mmHg, p = 0.04). CONCLUSIONS: Vitamin D3 supplementation in doses
      equivalent to 942 IU/day improved isometric handgrip strength, but had no effect
      on glycaemic control in postmenopausal women with longstanding type 2 diabetes.

PMID- 26301065
TI  - Effect of zoledronic acid on serum calcium in Paget's disease patients after
      educational strategies to improve calcium and vitamin D supplementation.
AB  - OBJECTIVE: Bisphosphonates are the most effective therapeutic agents in patients
      with Paget's disease of bone. As a result of their inhibition of osteoclastic
      activity, hypocalcemia of variable frequency and severity following intravenous
      bisphosphonate therapy has been reported. The present study assessed the effect
      of physician and patient education on adequate supplementation of calcium and
      vitamin D to reduce the potential risk of developing hypocalcemia following
      infusion of 5 mg zoledronic acid. METHODS: This was an open-label, multicenter,
      controlled registry trial in which patients with Paget's disease were treated
      with a single intravenous infusion of zoledronic acid. Physicians were provided
      with educational materials focusing on optimization of calcium and vitamin D
      supplementation following zoledronic infusion that they used to educate their
      patients. The primary safety variable was the percentage of patients with serum
      calcium level <2.07mmol/l 9-11 days after zoledronic acid infusion. RESULTS: A
      total of 75 patients were evaluable in the post dose hypocalcemia safety
      analysis. Of these, only 1 patient had treatment-emergent hypocalcemia, with a
      serum calcium level of 1.92 mmol/l 4 days following therapy. Hypocalcemia-related
      symptoms were not reported in this patient and the serum calcium returned to
      normal range at 2.17 mmol/l within 1 week on oral calcium supplementation.
      CONCLUSIONS: These results suggest that, with optimization of calcium and vitamin
      D supplementation by physician and patient education, hypocalcemia is an
      infrequent occurrence following zoledronic acid infusion.

PMID- 26301067
TI  - European Union pharmacovigilance capabilities: potential for the new legislation.
AB  - European Directives and Regulations introduced between late 2010 and 2012 have
      substantially overhauled pharmacovigilance processes across the European Union
      (EU). In this review, the implementation of the pharmacovigilance legislative
      framework by EU regulators is examined with the aim of mapping Directive
      2010/84/EU and Regulation EC No. 1235/2010 against their aspired objectives of
      strengthening and rationalizing pharmacovigilance in the EU. A comprehensive
      review of the current state of affairs of the progress made by EU regulators is
      presented in this paper. Our review shows that intense efforts by regulators and
      industry to fulfil legislative obligations have resulted in major positive shifts
      in pharmacovigilance. Harmonized decision making, transparency in decision
      processes with patient involvement, information accessibility to the public,
      patient adverse drug reaction reporting, efforts in communication and enhanced
      cooperation between member states to maximize resource utilization and minimize
      duplication of efforts are observed. 

PMID- 26301066
TI  - Anatomy of success: 100 most cited articles in diabetes research.
AB  - INTRODUCTION: The number of citations an article receives is an important
      indication of its impact and its contribution to academia. There is a paucity of
      literature concerning top article citations in diabetes. The main objective of
      this investigation was to bridge this gap and to provide readers with a practical
      guide in evaluating diabetes literature. METHODS: Scopus Library was searched to
      determine the citations of all published diabetes articles. A total of 100
      articles were included in our investigation under the subject category 'Diabetes,
      diabetes mellitus, and diabetics'. Two databases were used to extract citations.
      We did not apply any time restriction in our search. The top 100 cited articles
      were selected and analyzed by two independent investigators. We extracted
      immediacy index from ResearchGate. RESULTS: The journal with the highest number
      of top 100 cited articles was The New England Journal of Medicine with 23,
      followed by 22 in Diabetes Care. The top article on the list received 17,779
      citations. A statistically significant association was found between the journal
      impact factor and the number of top 100 cited articles (p < 0.005). The United
      States had the highest number of articles (59). Contrary to bibliometric analyses
      published in other medical fields, the largest subset of the diabetes articles (n
      = 54) were published in the 10-year period between 2000 and 2009. CONCLUSION: Our
      analysis provides an insight on the citation frequency of top cited articles
      published in diabetes to help recognize the quality of the works, discoveries and
      the trends steering the study of diabetes.

PMID- 26301068
TI  - Coming safely to a stop: a review of platelet activity after cessation of
      antiplatelet drugs.
AB  - The platelet P2Y12 antagonists are widely used, usually in combination with
      aspirin, to prevent atherothrombotic events in patients with acute coronary
      syndromes during percutaneous coronary intervention and after placement of
      arterial stents. Inhibition by clopidogrel or prasugrel lasts for the lifetime of
      the affected platelets and platelet haemostatic function gradually recovers after
      stopping the drug, as new unaffected platelets are formed. The optimal durations
      for dual antiplatelet therapy are prescribed by clinical guidelines. Continuation
      beyond the recommended duration is associated with an increased mortality, mainly
      associated with major bleeding. Fear of a 'rebound' of prothrombotic platelet
      activity on stopping the drug has provoked much discussion and many studies.
      However, review of the available literature reveals no evidence for production of
      hyper-reactive platelets after cessation of clopidogrel in patients who are
      stable. Any increase in acute coronary and other vascular events after stopping
      seems most likely therefore to be due to premature discontinuation or disruption
      of treatment while thrombotic risk is still high. No difference in rebound was
      found with the newer P2Y12 inhibitors, although ticagrelor and prasugrel are more
      potent platelet inhibitors than clopidogrel. Recent randomized controlled trials
      confirm it is safe to stop the thienopyridine and continue with aspirin alone in
      most patients after the duration of treatment recommended by the guidelines.
      Decisions on when to stop therapy in individuals, however, remain challenging and
      there is a growing rationale for platelet testing to assist clinical judgement in
      certain situations such as patients stopping dual antiplatelet therapy before
      surgery or in individuals at highest bleeding or thrombotic risk. 

PMID- 26301069
TI  - Anti-dementia medications: current prescriptions in clinical practice and new
      agents in progress.
AB  - Almost three decades after the publication of the first clinical studies with
      tacrine, the pharmacological treatment of Alzheimer's disease (AD) remains a
      challenge. Randomized clinical trials have yielded evidence of significant -
      although modest and transient - benefit from cholinergic replacement therapy for
      people diagnosed with AD, and disease modification with antidementia compounds is
      still an urgent, unmet need. The natural history of AD is very long, and its
      pharmacological treatment must acknowledge different needs according to the stage
      of the disease process. Cognitive and functional deterioration evolves gradually
      since the onset of clinical symptoms, which may be preceded by several years or
      perhaps decades of silent, presymptomatic neurodegeneration. Therefore, the
      pharmacological treatment of AD must ideally comprise both a symptomatic effect
      to preserve or improve cognition and a disease-modifying effect to tackle the
      progression of the pathological process. Primary prevention is the ultimate goal,
      should these strategies be delivered to patients with preclinical AD. In this
      article, we briefly address the pharmaceutical compounds that are currently used
      for the symptomatic treatment of AD and discuss the ongoing strategies designed
      to modify its natural course. 

PMID- 26301070
TI  - Combination use of medicines from two classes of renin-angiotensin system
      blocking agents: risk of hyperkalemia, hypotension, and impaired renal function.
AB  - European and United States regulatory agencies recently issued warnings against
      the use of dual renin-angiotensin system (RAS) blockade therapy through the
      combined use of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II
      receptor blockers (ARBs) or aliskiren in any patient, based on absence of benefit
      for most patients and increased risk of hyperkalemia, hypotension, and renal
      failure. Special emphasis was made not to use these combinations in patients with
      diabetic nephropathy. The door was left open to therapy individualization,
      especially for patients with heart failure, when the combined use of an ARB and
      ACEI is considered absolutely essential, although renal function, electrolytes
      and blood pressure should be closely monitored. Mineralocorticoid receptor
      antagonists were not affected by this warning despite increased risk of
      hyperkalemia. We now critically review the risks associated with dual RAS
      blockade and answer the following questions: What safety issues are associated
      with dual RAS blockade? Can the safety record of dual RAS blockade be improved?
      Is it worth trying to improve the safety record of dual RAS blockade based on the
      potential benefits of the combination? Is dual RAS blockade dead? What is the
      role of mineralocorticoid antagonists in combination with other RAS blocking
      agents: RAAS blockade? 

PMID- 26301071
TI  - hERG potassium channel inhibition by ivabradine may contribute to QT prolongation
      and risk of torsades de pointes.

PMID- 26301072
TI  - Intracellular Ca(2+)-handling differs markedly between intact human muscle fibers
      and myotubes.
AB  - BACKGROUND: In skeletal muscle, intracellular Ca(2+) is an important regulator of
      contraction as well as gene expression and metabolic processes. Because of the
      difficulties to obtain intact human muscle fibers, human myotubes have been
      extensively employed for studies of Ca(2+)-dependent processes in human adult
      muscle. Despite this, it is unknown whether the Ca(2+)-handling properties of
      myotubes adequately represent those of adult muscle fibers. METHODS: To enable a
      comparison of the Ca(2+)-handling properties of human muscle fibers and myotubes,
      we developed a model of dissected intact single muscle fibers obtained from human
      intercostal muscle biopsies. The intracellular Ca(2+)-handling of human muscle
      fibers was compared with that of myotubes generated by the differentiation of
      primary human myoblasts obtained from vastus lateralis muscle biopsies. RESULTS:
      The intact single muscle fibers all demonstrated strictly regulated cytosolic
      free [Ca(2+)] ([Ca(2+)]i) transients and force production upon electrical
      stimulation. In contrast, despite a more mature Ca(2+)-handling in myotubes than
      in myoblasts, myotubes lacked fundamental aspects of adult Ca(2+)-handling and
      did not contract. These functional differences were explained by discrepancies in
      the quantity and localization of Ca(2+)-handling proteins, as well as
      ultrastructural differences between muscle fibers and myotubes. CONCLUSIONS:
      Intact single muscle fibers that display strictly regulated [Ca(2+)]i transients
      and force production upon electrical stimulation can be obtained from human
      intercostal muscle biopsies. In contrast, human myotubes lack important aspects
      of adult Ca(2+)-handling and are thus an inappropriate model for human adult
      muscle when studying Ca(2+)-dependent processes, such as gene expression and
      metabolic processes.

PMID- 26301074
TI  - Editorial.

PMID- 26301073
TI  - GRAF1 deficiency blunts sarcolemmal injury repair and exacerbates cardiac and
      skeletal muscle pathology in dystrophin-deficient mice.
AB  - BACKGROUND: The plasma membranes of striated muscle cells are particularly
      susceptible to rupture as they endure significant mechanical stress and strain
      during muscle contraction, and studies have shown that defects in membrane repair
      can contribute to the progression of muscular dystrophy. The synaptotagmin
      related protein, dysferlin, has been implicated in mediating rapid membrane
      repair through its ability to direct intracellular vesicles to sites of membrane
      injury. However, further work is required to identify the precise molecular
      mechanisms that govern dysferlin targeting and membrane repair. We previously
      showed that the bin-amphiphysin-Rvs (BAR)-pleckstrin homology (PH) domain
      containing Rho-GAP GTPase regulator associated with focal adhesion kinase-1
      (GRAF1) was dynamically recruited to the tips of fusing myoblasts wherein it
      promoted membrane merging by facilitating ferlin-dependent capturing of
      intracellular vesicles. Because acute membrane repair responses involve similar
      vesicle trafficking complexes/events and because our prior studies in GRAF1
      deficient tadpoles revealed a putative role for GRAF1 in maintaining muscle
      membrane integrity, we postulated that GRAF1 might also play an important role in
      facilitating dysferlin-dependent plasma membrane repair. METHODS: We used an in
      vitro laser-injury model to test whether GRAF1 was necessary for efficient muscle
      membrane repair. We also generated dystrophin/GRAF1 doubledeficient mice by
      breeding mdx mice with GRAF1 hypomorphic mice. Evans blue dye uptake and
      extensive morphometric analyses were used to assess sarcolemmal integrity and
      related pathologies in cardiac and skeletal muscles isolated from these mice.
      RESULTS: Herein, we show that GRAF1 is dynamically recruited to damaged skeletal
      and cardiac muscle plasma membranes and that GRAF1-depleted muscle cells have
      reduced membrane healing abilities. Moreover, we show that dystrophin depletion
      exacerbated muscle damage in GRAF1-deficient mice and that mice with
      dystrophin/GRAF1 double deficiency phenocopied the severe muscle pathologies
      observed in dystrophin/dysferlin-double null mice. Consistent with a model that
      GRAF1 facilitates dysferlin-dependent membrane patching, we found that GRAF1
      associates with and regulates plasma membrane deposition of dysferlin.
      CONCLUSIONS: Overall, our work indicates that GRAF1 facilitates dysferlin
      dependent membrane repair following acute muscle injury. These findings indicate
      that GRAF1 might play a role in the phenotypic variation and pathological
      progression of cardiac and skeletal muscle degeneration in muscular dystrophy
      patients.

PMID- 26301075
TI  - Treatment response, safety, and tolerability of paliperidone extended release
      treatment in patients recently diagnosed with schizophrenia.
AB  - OBJECTIVE: This study was designed to explore the efficacy and tolerability of
      oral paliperidone extended release (ER) in a sample of patients who were switched
      to flexible doses within the crucial first 5 years after receiving a diagnosis of
      schizophrenia. METHODS: Patients were recruited from 23 countries. Adults with
      nonacute but symptomatic schizophrenia, previously unsuccessfully treated with
      other oral antipsychotics, were transitioned to paliperidone ER (3-12 mg/day) and
      prospectively treated for up to 6 months. The primary efficacy outcome for
      patients switching for the main reason of lack of efficacy with their previous
      antipsychotic was at least 20% improvement in Positive and Negative Syndrome
      Scale (PANSS) total scores. For patients switching for other main reasons, such
      as lack of tolerability, compliance or 'other', the primary outcome was non
      inferiority in efficacy compared with the previous oral antipsychotic. RESULTS:
      For patients switching for the main reason of lack of efficacy, 63.1% achieved an
      improvement of at least 20% in PANSS total scores from baseline to endpoint. For
      each reason for switching other than lack of efficacy, efficacy maintenance after
      switching to paliperidone ER was confirmed. Statistically significant improvement
      in patient functioning from baseline to endpoint, as assessed by the Personal and
      Social Performance scale, was observed (p < 0.0001). Treatment satisfaction with
      prior antipsychotic treatment at baseline was rated 'good' to 'very good' by
      16.8% of patients, and at endpoint by 66.0% of patients treated with paliperidone
      ER. Paliperidone ER was generally well tolerated, with frequently reported
      treatment-emergent adverse events being insomnia, anxiety and somnolence.
      CONCLUSIONS: Flexibly dosed paliperidone ER was associated with clinically
      relevant symptomatic and functional improvement in recently diagnosed patients
      with non-acute schizophrenia previously unsuccessfully treated with other oral
      antipsychotics.

PMID- 26301076
TI  - Improvement of nonsuicidal self-injury following treatment with antipsychotics
      possessing strong D1 antagonistic activity: evidence from a report of three
      cases.
AB  - INTRODUCTION: There is no drug treatment for nonsuicidal self-injury (NSSI), a
      highly prevalent and burdensome symptom of several psychiatric diseases like
      posttraumatic stress disorder (PTSD), personality disorders, and major depression
      (MD). METHODS: Here, we present a retrospective series of three patients
      demonstrating a persistent remission in MD-associated NSSI in response to
      treatment with antipsychotics possessing marked D1 receptor antagonistic
      activity. RESULTS: To the best of the authors' knowledge, the case series
      presented is only the second clinical paper suggesting a role for D1 antagonists
      in NSSI drug therapy. CONCLUSIONS: Together with previously published data from
      rodent models, the findings suggest a role for D1 antagonists in NSSI drug
      therapy and hence for the D1 receptor in NSSI pathogenesis. This conclusion is
      limited by the facts that the patients presented here received polypharmacy and
      that the D1 receptor antagonistic antipsychotics suggested here as effective
      'anti-auto-aggressants' do not address D1 receptors only but multiple
      neurotransmitter receptors/systems.

PMID- 26301077
TI  - Antipsychotic therapeutic drug monitoring: psychiatrists' attitudes and factors
      predicting likely future use.
AB  - BACKGROUND: This study aimed to explore predictive factors for future use of
      therapeutic drug monitoring (TDM) and to further examine psychiatrists' current
      prescribing practices and perspectives regarding antipsychotic TDM using plasma
      concentrations. METHOD: A cross-sectional study for consultant psychiatrists
      using a postal questionnaire was conducted in north-west England. Data were
      combined with those of a previous London-based study and principal axis factor
      analysis was conducted to identify predictors of future use of TDM. RESULTS: Most
      of the 181 participants (82.9%, 95% confidence interval 76.7-87.7%) agreed that
      'if TDM for antipsychotics were readily available, I would use it'. Factor
      analysis identified five factors from the original 35 items regarding TDM. Four
      of the factors significantly predicted likely future use of antipsychotic TDM and
      together explained 40% of the variance in a multivariate linear regression model.
      Likely future use increased with positive attitudes and expectations, and
      decreased with potential barriers, negative attitudes and negative expectations.
      Scientific perspectives of TDM and psychiatrist characteristics were not
      significant predictors. CONCLUSION: Most senior psychiatrists indicated that they
      would use antipsychotic TDM if available. However, psychiatrists' attitudes and
      expectations and the potential barriers need to be addressed, in addition to the
      scientific evidence, before widespread use of antipsychotic TDM is likely in
      clinical practice.

PMID- 26301078
TI  - Concomitant use of two or more antipsychotic drugs is common in Sweden.
AB  - OBJECTIVES: To assess the prevalence of concomitant use of two or more
      antipsychotic drugs and other psychotropic drugs in the Swedish population.
      METHODS: Data for this observational cohort study were collected from the Swedish
      Prescribed Drug Register including all dispensed drugs to the entire Swedish
      population (9.4 million inhabitants). We identified all individuals with at least
      one dispensed prescription of antipsychotic drug during January to June 2008.
      After 12 months, a second exposure period was chosen. Individuals who were
      dispensed two or more antipsychotic drugs in both periods were considered long
      time users of antipsychotic polypharmacy. RESULTS: In 2008, 1.5% of the Swedish
      population was dispensed antipsychotic drugs, the majority (75%) using only one
      antipsychotic drug. Out of individuals who were dispensed 2 or more antipsychotic
      drugs during the first period, 62% also was also dispensed at least 2
      antipsychotic drugs during the second period. A total of 665 different unique
      combinations were used in 2008. Individuals prescribed two or more antipsychotic
      drugs during both periods were more often dispensed anxiolytics and sedatives
      than those who were dispensed only one antipsychotic drug. Elderly were dispensed
      antipsychotic drugs much more often than younger persons. CONCLUSIONS: In Sweden,
      25% of patients dispensed antipsychotic drugs receive a combination of two or
      more antipsychotic drugs. Individuals who are dispensed antipsychotic
      polypharmacy are more often dispensed anxiolytics and sedatives than those
      prescribed only one antipsychotic drug. Long-term observational studies are
      needed to assess the efficacy and safety of such combinations.

PMID- 26301079
TI  - Clozapine-induced stuttering: an estimate of prevalence in the west of Ireland.
AB  - OBJECTIVES: Clozapine is the most effective treatment available for treatment
      resistant schizophrenia; however, it is also associated with a large array of
      adverse effects that limits its tolerability. A number of previous case reports
      have noted an association between clozapine and stuttering, however the rate of
      this possible adverse effect is yet to be established. METHODS: In this paper, we
      present six cases of patients treated with clozapine who developed stuttering.
      RESULTS: Clozapine was associated with stuttering in 0.92% of individuals treated
      with clozapine in the region. Clozapine-induced stuttering was associated with an
      increase in treatment dose or with dose titration at initiation of clozapine in
      five individuals, with dose reduction or slower dose titration associated with a
      cessation of stuttering in these cases. CONCLUSIONS: This is the largest case
      series to date examining clozapine-induced stuttering and indicates that
      clozapine-induced stuttering is a relatively common adverse effect that can be
      managed by a slower titration of clozapine dosage or a modest reduction in dose
      in most cases.

PMID- 26301080
TI  - Effectiveness of ultra-rapid dose titration of clozapine for treatment-resistant
      bipolar mania: case series.
AB  - Treatment of severe and refractory manic episodes in hospital settings can
      occasionally be very difficult. In particular, severely excited patients showing
      aggressive, hostile, impulsive behaviours frequently require physical restraint
      and seclusion, high doses of antipsychotics and benzodiazepines, and sometimes,
      electroconvulsive therapy. Hospital stay is generally prolonged and such patients
      cause great emotional distress for other patients in the ward and clinical staff
      involved in their care. Here we report on three patients with a diagnosis of
      bipolar disorder and one patient with a diagnosis of schizoaffective disorder
      bipolar subtype, all of whom were hospitalized for severe manic episodes with
      psychotic features. These patients were extremely difficult to manage in the ward
      as no response could be obtained in the first week of treatment despite high
      doses of antipsychotics and benzodiazepine administration. The introduction and
      rapid titration of clozapine proved remarkably effective and was well tolerated
      in the acute management of these patients. We observed that clozapine had a
      superior and fast mood stabilization effect with rapid titration and could be
      extremely helpful in the management of such patients. 

PMID- 26301081
TI  - Agomelatine and migraine management: a successfully treated case series.

PMID- 26301082
TI  - Association of quetiapine with ischemic brain stem stroke: a case report and
      discussion.

PMID- 26301083
TI  - The role of alpha-actinin-4 in human kidney disease.
AB  - Mutations in the Alpha-actinin-4 gene (ACTN4) cause a rare form of familial focal
      segmental glomerulosclerosis in humans. Individuals with kidney disease
      associated ACTN4 mutations tend to have mild to moderate proteinuria, with many
      developing decreased kidney function progressing to end stage kidney disease. All
      of the disease-causing ACTN4 mutations identified to date are located within the
      actin-binding domain of the encoded protein, increasing its binding affinity to F
      actin and leading to abnormal actin rich cellular aggregates. The identification
      of ACTN4 mutations as a cause of human kidney disease demonstrates a key cellular
      pathway by which alterations in cytoskeletal behavior can mediate kidney disease.
      Here we review the studies relevant to ACTN4 and its role in mediating kidney
      disease. 

PMID- 26301084
TI  - Ferulic acid combined with aspirin demonstrates chemopreventive potential towards
      pancreatic cancer when delivered using chitosan-coated solid-lipid nanoparticles.
AB  - BACKGROUND: The overall goal of this study was to demonstrate potential
      chemopreventive effects of ferulic acid (FA), an antioxidant, combined with
      aspirin (ASP), a commonly used anti-inflammatory drug for pancreatic cancer
      chemoprevention, using a novel chitosan-coated solid lipid nanoparticles (c-SLN)
      drug delivery system encapsulating FA and ASP. RESULTS: Our formulation
      optimization results showed that c-SLNs of FA and ASP exhibited appropriate
      initial particle sizes in range of 183 +/- 46 and 229 +/- 67 nm, encapsulation
      efficiency of 80 and 78 %, and zeta potential of 39.1 and 50.3 mV, respectively.
      In vitro studies were conducted to measure growth inhibition and degree of
      apoptotic cell death induced by either FA or ASP alone or in combination. Cell
      viability studies demonstrated combinations of low doses of free FA (200 uM) and
      ASP (1 mM) significantly reduced cell viability by 45 and 60 % in human
      pancreatic cancer cells MIA PaCa-2 and Panc-1, respectively. However, when
      encapsulated within c-SLNs, a 5- and 40-fold decreases in dose of FA (40 uM) and
      ASP (25 uM) was observed which was significant. Furthermore, increased apoptosis
      of 35 and 31 % was observed in MIA PaCa-2 and Panc-1 cells, respectively. In vivo
      studies using oral administration of combinations of 75 and 25 mg/kg of FA and
      ASP c-SLNs to MIA PaCa-2 pancreatic tumor xenograft mice model suppressed the
      growth of the tumor by 45 % compared to control, although this was not
      statistically significant. In addition, the immunohistochemical analysis of tumor
      tissue showed significant decrease in expression of proliferation proteins PCNA
      and MKI67, and also increased expression of apoptotic proteins p-RB, p21, and p
      ERK1/2 indicating the pro-apoptotic role of the regimen. CONCLUSION: Combination
      of FA and ASP delivered via a novel nanotechnology-based c-SLN formulation
      demonstrates potential for pancreatic cancer chemoprevention and could be a
      promising area for future studies.

PMID- 26301085
TI  - The challenge of benchmarking health systems: is ICT innovation capacity more
      systemic than organizational dependent?
AB  - The article by Catan et al. presents a benchmarking exercise comparing Israel and
      Portugal on the implementation of Information and Communication Technologies in
      the healthcare sector. Special attention was given to e-Health and m-Health. The
      authors collected information via a set of interviews with key stakeholders. They
      compared two different cultures and societies, which have reached slightly
      different implementation outcomes. Although the comparison is very enlightening,
      it is also challenging. Benchmarking exercises present a set of challenges, such
      as the choice of methodologies and the assessment of the impact on organizational
      strategy. Precise benchmarking methodology is a valid tool for eliciting
      information about alternatives for improving health systems. However, many
      beneficial interventions, which benchmark as effective, fail to translate into
      meaningful healthcare outcomes across contexts. There is a relationship between
      results and the innovational and competitive environments. Differences in
      healthcare governance and financing models are well known; but little is known
      about their impact on Information and Communication Technology implementation.
      The article by Catan et al. provides interesting clues about this issue. Public
      systems (such as those of Portugal, UK, Sweden, Spain, etc.) present specific
      advantages and disadvantages concerning Information and Communication Technology
      development and implementation. Meanwhile, private systems based fundamentally on
      insurance packages, (such as Israel, Germany, Netherlands or USA) present a
      different set of advantages and disadvantages - especially a more open context
      for innovation. Challenging issues from both the Portuguese and Israeli cases
      will be addressed. Clearly, more research is needed on both benchmarking
      methodologies and on ICT implementation strategies. 

PMID- 26301088
TI  - In conversation with...Jim Sibree Milledge.

PMID- 26301086
TI  - A biopsychosocial approach to primary hypothyroidism: treatment and harms data
      from a randomized controlled trial.
AB  - BACKGROUND: Hypothyroidism is a common endocrine condition. There is evidence to
      suggest that, for a proportion of sufferers, the standard medical treatment does
      not completely reverse the constitutional and neuropsychiatric symptoms brought
      about by this condition. The management of hypothyroidism follows a biomedical
      model with little consideration given to alternative management approaches. There
      exists anecdotal evidence and case reports supporting the use of a
      biopsychosocial-based intervention called Neuro-Emotional Technique (NET) for
      this population. The aim of this study was to explore the potential short-medium
      term clinical efficacy and safety of NET for individuals with primary
      hypothyroidism.DesignPlacebo-controlled, blinded, parallel groups, randomized
      trial. METHODS: Ninety adults with a diagnosis of primary hypothyroidism were
      recruited from Sydney, Australia. Blinded participants were randomized to either
      the NET or placebo group and received ten intervention sessions over a six week
      period. The primary outcome involved the measurement of states of depression
      using the DASS-42 questionnaire. Secondary outcomes included thyroid function,
      thyroid autoimmunity testing, SF-36v2 questionnaire, resting heart rate and
      temperature measurement. Outcomes were obtained at baseline, seven weeks and six
      months. Questionnaires were completed at the private clinics, and serum measures
      were obtained and analysed at commercial pathology company locations. Heart rate
      and temperature were also measured daily by participants. Linear mixed-effects
      models were used to analyse the continuous outcomes. Unadjusted odds ratios with
      95% confidence intervals were calculated for the binary outcomes. RESULTS:
      Participants were randomly allocated to the NET (n=44) and placebo (n=46) groups.
      A proportion of the sample displayed neuropsychiatric disturbances and
      alterations in quality of life measures at baseline. There were no statistically
      significant or clinically relevant changes in the primary or secondary outcomes
      between the NET and placebo groups at time seven weeks or six months. There were
      a few short-lived minor adverse events reported in both the NET and placebo
      groups that coincided with the application of the intervention. CONCLUSIONS: The
      application of the NET intervention appears to be safe, but did not confer any
      clinical benefit to the participants in this study and is unlikely to be of
      therapeutic use in a hypothyroid population. CLINICAL TRIALS REGISTRATION NUMBER:
      Australian and New Zealand Clinical Trials Registry Number: 12607000040460.

PMID- 26301087
TI  - Variability in vascular smooth muscle cell stretch-induced responses in 2D
      culture.
AB  - The pulsatile nature of blood flow exposes vascular smooth muscle cells (VSMCs)
      in the vessel wall to mechanical stress, in the form of circumferential and
      longitudinal stretch. Cyclic stretch evokes VSMC proliferation, apoptosis,
      phenotypic switching, migration, alignment, and vascular remodeling. Given that
      these responses have been observed in many cardiovascular diseases, a defined
      understanding of their underlying mechanisms may provide critical insight into
      the pathophysiology of cardiovascular derangements. Cyclic stretch-triggered VSMC
      responses and their effector mechanisms have been studied in vitro using tension
      systems that apply either uniaxial or equibiaxial stretch to cells grown on an
      elastomer-bottomed culture plate and ex vivo by stretching whole vein segments
      with small weights. This review will focus mainly on VSMC responses to the in
      vitro application of mechanical stress, outlining the inconsistencies in acquired
      data, and comparing them to in vivo or ex vivo findings. Major discrepancies in
      data have been seen in mechanical stress-induced proliferation, apoptosis, and
      phenotypic switching responses, depending on the stretch conditions. These
      discrepancies stem from variations in stretch conditions such as degree, axis,
      duration, and frequency of stretch, wave function, membrane coating, cell type,
      cell passage number, culture media content, and choice of in vitro model. Further
      knowledge into the variables that cause these incongruities will allow for
      improvement of the in vitro application of cyclic stretch. 

PMID- 26301089
TI  - What roles do accredited drug dispensing outlets in Tanzania play in facilitating
      access to antimicrobials? Results of a multi-method analysis.
AB  - BACKGROUND: People in low-income countries purchase a high proportion of
      antimicrobials from retail drug shops, both with and without a prescription.
      Tanzania's accredited drug dispensing outlet (ADDO) program includes dispenser
      training, enforcement of standards, and the legal right to sell selected
      antimicrobials. We assessed the role of ADDOs in facilitating access to
      antimicrobials. METHODS: We purposively chose four regions, randomly selected
      three districts and five wards per district. Study methods included interviews at
      1200 households regarding care-seeking for acute illness and knowledge about
      antimicrobials; mystery shoppers visiting 306 ADDOs posing as a caregiver of a
      child with 1) pneumonia, 2) mild acute respiratory infection (ARI), or 3) a runny
      nose and request for co-trimoxazole; and audits of antimicrobial availability and
      prices at 84 public health facilities (PHFs) and 96 ADDOs. RESULTS: Four hundred
      sixty seven (76 %) members from 367 (77 %) households had recently sought care
      outside the home for acute illness; 128 had purchased antimicrobials, of which 61
      % had been recommended by a doctor or nurse and 32 % by an ADDO dispenser. Only
      29 % obtained the antimicrobial at a PHF, whereas, 48 % purchased them at an
      ADDO. Most thought that ADDOs are convenient place for care, usually have needed
      medicines, and have high quality services and products, contrasting with 66 % who
      reported dissatisfaction with PHF waiting times and 56 % with medicine
      availability. One-third (34 %) of mystery shoppers presenting the mild ARI
      scenario were inappropriately sold an antimicrobial and 85 % were sold one on
      request; encouragingly, 99 % presenting a case of pneumonia received either an
      antimicrobial, referral to a trained provider, or request to bring the child for
      examination. Overall, 63 and 60 % of the 15 tracer antimicrobials were in stock
      in ADDOs and PHFs, respectively; ADDOs had significantly more antimicrobial
      formulations for children available (83 vs. 51 %). Of 369 records of
      antimicrobial sales in 47 ADDOs, 63 % were dispensed on prescription. CONCLUSION:
      ADDOs have increased access to antimicrobials in Tanzania. Community members see
      them as integral to the health system. Antimicrobials are overused due to poor
      ADDO dispensing, poor PHF prescribing, and inappropriate public demand. Multi
      pronged interventions are needed to address all determinants.

PMID- 26301090
TI  - Clinical management and associated costs for moderate and severe Alzheimer's
      disease in urban China: a Delphi panel study.
AB  - BACKGROUND: Healthcare resource utilisation for Alzheimer's disease (AD) in China
      is not well understood. This Delphi panel study aimed to describe the clinical
      management pathways for moderate and severe AD patients in urban China and to
      define the amount and cost of healthcare resources used. METHODS: A panel of 11
      experts was recruited from urban China to participate in two rounds of
      preparatory interviews. In the first round, 9 physicians specialised in dementia
      gave a qualitative description of the clinical management of AD patients. In the
      second round, 2 hospital administrators were asked about the cost of AD
      management and care. Results from the interviews were discussed by the experts in
      a Delphi panel meeting, where consensus was reached on quantitative aspects of AD
      management, including the rate of healthcare resource utilisation, the respective
      unit costs and caregiving time. RESULTS: Interviewees reported that mild AD is
      under-recognised in China; most patients are diagnosed with moderate to severe
      AD. Loss of independence and agitation/aggression are the main drivers for
      healthcare resource utilisation and contribute to a heavier caregiver burden. It
      was estimated that 70 % moderate AD patients are independent/non-aggressive at
      the time of diagnosis, 15 % are independent/aggressive, 10 % are dependent/non
      aggressive, and 5 % are dependent/aggressive. Dependent/aggressive AD patients
      are more likely to be hospitalised (70-90 %) than accepted in a nursing home (0
      20 %), while the opposite is true for dependent/non-aggressive patients (5-35 %
      for hospitalisation vs. 80 % for nursing home). Independent AD patients require 1
      3 hours/day of caregiver time, while dependent patients can require up to 12-15
      hours/day. Experts agreed that AD complicates the management of age-related
      comorbidities, found in 70-80 % of all AD patients, increasing the frequency and
      cost of hospitalisation. CONCLUSIONS: The Delphi panel approach was an efficient
      method of gathering data about the amount of healthcare resources used and
      associated costs for moderate and severe AD patients in urban China. The results
      of this study provide a useful source of information for decision makers to
      improve future healthcare policies and resource planning, as well as to perform
      economic evaluations of AD therapies.

PMID- 26301091
TI  - Chemical composition, energy and amino acid digestibility in double-low rapeseed
      meal fed to growing pigs.
AB  - BACKGROUND: The nutritional value of rapeseed meal may be variable due to the
      variation of its chemical composition. And a precise understanding of the
      nutritional value of an ingredient is beneficial for the accurate diet
      formulation and reduction of feed costs. This study was conducted to determine
      the chemical composition, digestible energy (DE) and metabolizable energy (ME)
      content, and apparent ileal digestibility (AID) and standardized ileal
      digestibility (SID) of amino acids (AA) for growing pigs. Thirteen solvent
      extracted double-low rapeseed meal (DLRSM) samples were obtained from the main
      double-low rapeseed producing areas in China. METHODS: The DE and ME contents of
      the 13 DLRSM samples were measured in growing pigs (six pigs per DLRSM sample,
      average initial body weight (BW) = 48.3 kg). The AID and SID of AA of 10 DLRSM
      samples were determined in 12 crossbred barrows (average initial BW = 35.3 kg) by
      using two 6 * 6 Latin square designs. Each Latin square comprised one N-free diet
      and 5 DLRSM test diets. RESULTS: The chemical composition of DLRSM varied among
      samples, and the coefficient of variation was greater than 10 % for ether extract
      (EE), neutral detergent fiber (NDF), acid detergent fiber (ADF), calcium (Ca),
      and total glucosinolates. The AA content of DLRSM varied among samples especially
      for lysine (Lys) and methionine (Met). On a dry matter (DM) basis, the apparent
      total tract digestibility (ATTD) of gross energy (GE), the DE and ME and the
      ME:DE ratio of DLRSM averaged 62.39 %, 2862 kcal/kg and 2723 kcal/kg, and 94.95
      %, respectively. The mean value of SID of Lys was 70.52 % which varied from 66.54
      76.54 %. The SID of crude protein (CP), Met, and threonine (Thr) averaged 72.81
      %, 82.41 %, and 69.76 %, respectively. CONCLUSIONS: There was great variability
      in chemical composition especially in the concentration of EE, NDF and ADF, but
      no significant differences in energy content of the DLRSM samples were observed.
      In addition, the AID and SID of all AA were relatively similar among DLRSM
      samples except for that of Lys.

PMID- 26301092
TI  - Clays as dietary supplements for swine: A review.
AB  - Clays are crystalline, hydrated aluminosilicate molecules composed of alkali and
      alkaline earth cations along with small amounts of various other elements. The
      best-known are montmorillonite, smectite, illite, kaolinite, biotite and
      clinoptilolite. The molecules in these clays are arranged in three-dimensional
      structures creating internal voids and channels capable of trapping a wide
      variety of molecules. As a result of this structure, clay minerals are regarded
      as a simple and effective tool for the prevention of the negative effects of many
      toxic compounds. Dietary supplementation with clays has been shown to improve
      weight gain and feed conversion in pigs. Where improvements in performance have
      been noted, one of the most likely explanations for the improvement is the fact
      clays increase nutrient digestibility. Clays reduce the speed of passage of feed
      along the digestive tract which allows more time for digestion. Feeding clays
      also causes morphological changes in the intestinal mucosa such as an increase in
      villus height and an increase in the villus height to crypt depth ratio. These
      changes increase the surface area of the gastrointestinal tract thus increasing
      nutrient digestibility. Several studies have indicated that feeding clay reduces
      the incidence, severity and duration of diarrhea in pigs. The mechanism for the
      reduction in diarrhea is likely due to increases in the numbers of Bifidobacteria
      and Lactobacillus and decreases in Clostridia and E. coli in the small intestine
      of pigs fed clays. In addition, the numbers of pigs born alive and weaned, birth
      weight and weaning weight have been shown to be higher for sows fed clays.
      Several studies have indicated that clays can help mitigate the effects of
      mycotoxins. The aim of the present review is to focus on the various clays which
      have been given attention in recent research and to discuss their potential to
      improve pig performance. 

PMID- 26301093
TI  - Anchoring Effects of Surface Chemistry on Gold Nanorods: Modulates Autophagy.
AB  - Gold nanorods (Au NRs) have been receiving extensive attention owing to their
      extremely attractive properties which make them suitable for various biomedical
      applications. Au NRs could induce nano-toxicity, but this trouble could turn into
      therapeutic potential through tuning the autophagy. However, the autophagy
      inducing activity and mechanism of Au NRs is still unclear. Here we showed that
      surface chemical modification can tune the autophagy-inducing activity of Au NRs
      in human lung adenocarcinoma A549 cells. CTAB-coated Au NRs induce remarkable
      levels of autophagy activity as evidenced by LC3-II conversion and p62
      degradation, while PSS- and PDDAC-coated Au NRs barely induce autophagy. More
      importantly, we also demonstrated that the AKT-mTOR signaling pathway was
      responsible for CTAB-coated Au NRs-induced autophagy. We furthermore showed that
      CTAB-coated Au NRs also induces autophagy in human fetal lung fibroblast MRC-5
      cells in a time-dependent manner. This study unveils a previously unknown
      function for Au NRs in autophagy induction, and provides a new insight for
      designing surface modifications of Au NRs for biomedical applications.

PMID- 26301094
TI  - Suspected anemia caused by maternal anti-Jra antibodies: a case report.
AB  - Most cases of hemolytic disease of the newborn associated with anti-Jra are mild.
      However, rare cases of hydrops fetalis and severe anemia have been reported. We
      treated a neonate with anemia who was born with maternal anti-Jra, which were
      detected in the umbilical cord plasma. The Jra antigens in the neonate core blood
      red blood cells (RBCs) exhibited extremely weak reactivity to PEG-IAT, an anti
      Jra reagent. However, upon re-examination of Jra antigen using PEG-IAT at 3
      months postpartum, positivity was observed. Thereafter, upon performing PCR-SSP
      analysis of blood relatives targeting ABCG2 at positions 376 and 421, we found
      that the mother was Jr(a-) with 376 T homozygosity, whereas the father was Jr(a+)
      with 376 C homozygosity and a carrier of a 421 C > A mutation. The first sibling,
      like the propositus, was Jr(a+), exhibiting 376 CT heterozygosity. However, the
      first sibling carried a 421 C > A mutation, whereas the propositus had no
      mutation at position 421. Setting the normal Jra (a+) type (376 C, 421 C) to 100
      %, we identified the amount of Jra in RBC using FCM to be 82 % in the father, 31
      % in the first sibling, and 69 % in the propositus. Furthermore, upon comparing
      peripheral blood and myelograms of the neonate at the time of birth, we found a
      low myeloid cells/erythroid cells ratio, undifferentiated erythroblasts, and
      reduced megakaryocytes. On the basis of these findings, we suggest that cell
      surface antigen is involved in the HDN caused by anti-Jra, and that a
      cytodifferentiation abnormality is present in the hematopoietic system. 

PMID- 26301095
TI  - Detection of coagulopathy in paediatric heart surgery [DECISION study]: study
      protocol.
AB  - BACKGROUND: Each year in the UK, ~3000 children undergo major cardiac surgery
      requiring cardiopulmonary bypass. Approximately 40 % of these experience
      excessive bleeding necessitating red cell transfusion or treatment with other
      blood components. A further 40 % receive blood components because of the
      perception by clinicians that the risk of bleeding is high. Excessive bleeding
      and treatment with red cell transfusion or blood components are associated with
      post-operative complications such as infection and renal injury and are
      independently associated with increased morbidity and mortality. Abnormalities in
      blood coagulation are a major cause of excessive bleeding after cardiac surgery
      in children. However, the extent of these abnormalities varies between children
      and their characteristics may change rapidly during surgery. In adults undergoing
      cardiac surgery, rapid testing of blood coagulation using techniques such as
      thromboelastometry may assist the selection of appropriate blood component
      treatments. In some sub-groups of adults, this improves clinical outcomes. Rapid
      testing of blood coagulation in children undergoing cardiac surgery has not been
      evaluated fully. METHODS/DESIGN: The DECISION study is a prospective, single
      centre, observational study that aims to assess the utility of rapid testing of
      blood coagulation in children undergoing cardiac surgery. This will be achieved
      by testing blood samples from 200 children obtained immediately before, and after
      cardiac surgery. The blood samples will be analysed in parallel using
      thromboelastometry and reference laboratory tests of blood coagulation. The
      primary clinical outcome will be clinical concern about bleeding, defined as a
      composite of either excessive blood loss or the use of a pro-haemostatic
      treatment outside of standard treatment protocols because of perceived high risk
      of excessive bleeding. The reference laboratory test results will be used to
      describe the patterns of abnormalities in blood coagulation in children and will
      be compared to the thromboelastometry test results to determine the diagnostic
      accuracy of the thromboelastometry tests. We will estimate how well the reference
      and thromboelastometry test results predict clinical concern about bleeding.
      DISCUSSION: The DECISION study will identify the most useful thromboeastometry
      tests of blood coagulation for the prediction of excessive bleeding in children
      after cardiac surgery and will inform the design of future randomised controlled
      trials. TRIAL REGISTRATION: The trail was registered as ISRCTN55439761 on 23(rd)
      April 2015.

PMID- 26301096
TI  - Fabrication and characterization of a polysulfone-graphene oxide nanocomposite
      membrane for arsenate rejection from water.
AB  - BACKGROUND: Nowadays, study and application of modified membranes for water
      treatment have been considered significantly. The aim of this study was to
      prepare and characterize a polysulfone (PSF)/graphene oxide (GO) nanocomposite
      membrane and to evaluate for arsenate rejection from water. MATERIALS AND
      METHODS: The nanocomposite PSF/GO membrane was fabricated using wet phase
      inversion method. The effect of GO on the synthesized membrane morphology and
      hydrophilicity was studied by using FE-SEM, AFM, contact angle, zeta potential,
      porosity and pore size tests. The membrane performance was also evaluated in
      terms of pure water flux and arsenate rejection. RESULTS: ATR-FTIR confirmed the
      presence of hydrophilic functional groups on the surface of the prepared GO. FE
      SEM micrographs showed that with increasing GO content in the casting solution,
      the sub-layer structure was enhanced and the drop like voids in the pure PSF
      membrane changed to macrovoids in PSF/GO membrane along with increase in
      porosity. AFM images indicated lower roughness of modified membrane compared to
      pure PSF membrane. Furthermore, contact angle measurement and permeation
      experiment showed that by increasing GO up to 1 wt%, membrane hydrophilicity and
      pure water flux were increased. For PSF/GO-1, pure water flux was calculated
      about 50 L/m(2)h at 4 bar. The maximum rejection was obtained by PSF/GO-2 about
      83.65 % at 4 bar. Moreover, it was revealed that arsenate rejection depended on
      solution pH values. It was showed that with increasing pH, the rejection
      increased. CONCLUSIONS: This study showed that application of GO as an additive
      to PSF casting solution could enhance the membrane hydrophilicity, porosity, flux
      and arsenate rejection.

PMID- 26301097
TI  - Algorithms for personalized therapy of type 2 diabetes: results of a web-based
      international survey.
AB  - OBJECTIVE: In recent years increasing interest in the issue of treatment
      personalization for type 2 diabetes (T2DM) has emerged. This international web
      based survey aimed to evaluate opinions of physicians about tailored therapeutic
      algorithms developed by the Italian Association of Diabetologists (AMD) and
      available online, and to get suggestions for future developments. Another aim of
      this initiative was to assess whether the online advertising and the survey would
      have increased the global visibility of the AMD algorithms. RESEARCH DESIGN AND
      METHODS: The web-based survey, which comprised five questions, has been available
      from the homepage of the web-version of the journal Diabetes Care throughout the
      month of December 2013, and on the AMD website between December 2013 and
      September 2014. Participation was totally free and responders were anonymous.
      RESULTS: Overall, 452 physicians (M=58.4%) participated in the survey.
      Diabetologists accounted for 76.8% of responders. The results of the survey show
      wide agreement (>90%) by participants on the utility of the algorithms proposed,
      even if they do not cover all possible needs of patients with T2DM for a
      personalized therapeutic approach. In the online survey period and in the months
      after its conclusion, a relevant and durable increase in the number of unique
      users who visited the websites was registered, compared to the period preceding
      the survey. CONCLUSIONS: Patients with T2DM are heterogeneous, and there is
      interest toward accessible and easy to use personalized therapeutic algorithms.
      Responders opinions probably reflect the peculiar organization of diabetes care
      in each country.

PMID- 26301098
TI  - Utility of current obesity thresholds in signaling diabetes risk in the James Bay
      Cree of Eeyou Istchee.
AB  - OBJECTIVE: The anthropometric thresholds signaling type 2 diabetes risk have not
      been well defined for Aboriginal communities. This study examined current
      thresholds in terms of ability to capture diabetes risk in the Cree of Eeyou
      Istchee in northern Quebec, Canada. RESEARCH DESIGN AND METHODS: The study cohort
      for this analysis included adult participants from the Nituuchischaayihtitaau
      Aschii Multi-Community Environment and Health Study with complete data on
      anthropometric measures, fasting glucose, and insulin. Diabetes risk was defined
      as Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) value >2.
      Positive and negative likelihood ratios (PLR, NLR) of existing obesity thresholds
      were evaluated (WHO; International Diabetes Federation, IDF; Adult Treatment
      Panel III, ATP III). Receiver operating curves were examined to estimate optimal
      thresholds. In a sensitivity analysis, diabetes risk was defined as HOMA-IR >2.7.
      RESULTS: The WHO 30 kg/m(2) body mass index (BMI) threshold performed well in
      women (PLR 5.56, 95% CI 1.95 to 15.9; NLR 0.24, 95% CI 0.19 to 0.31) and men (PLR
      7.51, 95% CI 2.94 to 19.2; NLR 0.33, 95% CI 0.27 to 0.41). It was close to the
      estimated optimal threshold (28.5 kg/m(2)). The ATP III waist circumference
      threshold (102 cm) performed well in men (PLR 4.64, 95% CI 2.47 to 8.71; NLR
      0.21, 95% CI 0.16 to 0.28) and was close to the estimated optimal threshold (101
      cm). With diabetes risk defined at HOMA-IR >2.7, PLR values were slightly lower
      with narrower 95% CIs and optimal thresholds were slightly higher; PLR values
      remained above 3. For other current thresholds, estimated optimal values were
      higher and none had a PLR above 2. CONCLUSIONS: A BMI of 30 kg/m(2) in women and
      men, and a 102 cm waist circumference in men, are meaningful obesity thresholds
      in this Aboriginal population. Other thresholds require a further evaluation.

PMID- 26301099
TI  - Exercise-based cardiac rehabilitation after heart valve surgery: cost analysis of
      healthcare use and sick leave.
AB  - BACKGROUND: Owing to a lack of evidence, patients undergoing heart valve surgery
      have been offered exercise-based cardiac rehabilitation (CR) since 2009 based on
      recommendations for patients with ischaemic heart disease in Denmark. The aim of
      this study was to investigate the impact of CR on the costs of healthcare use and
      sick leave among heart valve surgery patients over 12 months post surgery.
      METHODS: We conducted a nationwide survey on the CR participation of all patients
      having undergone valve surgery between 1 January 2011 and 30 June 2011 (n=667).
      Among the responders (n=500, 75%), the resource use categories of primary and
      secondary healthcare, prescription medication and sick leave were analysed for CR
      participants (n=277) and non-participants (n=223) over 12 months. A difference-in
      difference analysis was undertaken. All estimates were presented as the means per
      patient (95% CI) based on non-parametric bootstrapping of SEs. RESULTS: Total
      costs during the 12 months following surgery were ?16 065 per patient (95% CI 13
      730 to 18 399) in the CR group and ?15 182 (12 695 to 17 670) in the non-CR
      group. CR led to 5.6 (2.9 to 8.3, p<0.01) more outpatient visits per patient. No
      statistically significant differences in other cost categories or total costs
      ?1330 (-4427 to 7086, p=0.65) were found between the groups. CONCLUSIONS: CR, as
      provided in Denmark, can be considered cost neutral. CR is associated with more
      outpatient visits, but CR participation potentially offsets more expensive
      outpatient visits. Further studies should investigate the benefits of CR to heart
      valve surgery patients as part of a formal cost-utility analysis.

PMID- 26301100
TI  - Safety and efficacy of hCDR1 (Edratide) in patients with active systemic lupus
      erythematosus: results of phase II study.
AB  - OBJECTIVE: To evaluate the safety and efficacy of hCDR1 (Edratide) in patients
      with systemic lupus erythematosus (SLE). METHODS: Patients (n=340) with SLE >=4
      ACR criteria (4-11, mean 7) with active disease (SLEDAI-2K of 6-12). Patients
      were on average 7.1 years post-diagnosis and their organ involvement was mainly
      musculoskeletal, mucocutaneous and haematologic. Placebo or Edratide was
      administered subcutaneously weekly at doses of 0.5, 1.0 or 2.5 mg. The co-primary
      endpoints were SLEDAI-2K SLE Disease Activity and Adjusted Mean SLEDAI (AMS)
      reduction in patients compared with controls using a landmark analysis. Secondary
      outcomes were improvement in British Isles Lupus Assessment Group (BILAG)
      Responder Index and medicinal flare analysis. RESULTS: Edratide was safe and well
      tolerated. The primary endpoints based solely on SLEDAI-2K and AMS were not met.
      The secondary predefined endpoint, BILAG, was met for the 0.5 mg Edratide arm in
      the intention to treat (ITT) cohort (N=316) (OR=2.09, p=0.03) with trends in the
      1.0 and 2.5 mg doses. There was also a positive trend in the Composite SLE
      Responder Index of the ITT cohort. Post hoc analysis showed that the BILAG
      secondary endpoint was also met for the 0.5 mg Edratide for a number of subgroup
      dose levels, including low or no steroids, seropositivity and patients with 2
      grade BILAG improvement. CONCLUSIONS: The favourable safety profile and
      encouraging clinically significant effects noted in some of the endpoints support
      the need for additional longer term Edratide studies that incorporate recent
      advances in the understanding and treatment of SLE, including steroid treatment
      algorithms, and using a composite primary endpoint which is likely to include
      BILAG. TRIAL REGISTRATION NUMBER: NCT00203151.

PMID- 26301102
TI  - Spectral-Domain Optical Coherence Tomography of Preclinical Chloroquine
      Maculopathy in Egyptian Rheumatoid Arthritis Patients.
AB  - Purpose. To evaluate the role of spectral-domain optical coherence tomography (SD
      OCT) in early detection of Chloroquine maculopathy in rheumatoid arthritis (RA)
      patients. Methods. 40 left eyes of 40 female rheumatoid arthritis patients who
      received treatment chloroquine for more than one year were recruited in the
      study. All patients had no symptoms or signs of Chloroquine retinopathy. They
      were evaluated using SD-OCT, where the Central Foveal Thickness (CFT), parafoveal
      thickness and perifoveal thickness, average Retinal Nerve Fiber Layer (RNFL)
      thickness, and Ganglion Cell Complex (GCC) measurements were measured and
      compared to 40 left eyes of 40 normal females. Results. The mean CFT was found to
      be thinner in the Chloroquine group (238.15 um +/- 22.49) than the normal
      controls (248.2 um +/- 19.04), which was statistically significant (p value =
      0.034). The mean parafoveal thickness was lesser in the Chloroquine group than
      the control group in all quadrants (p value <0.05). The perifoveal thickness in
      both groups showed no statistically significant difference (p value >0.05) in all
      quadrants. No significant difference was detected between the two groups
      regarding RNFL, GCC, or IS/OS junction. Conclusions. Preclinical Chloroquine
      toxicity can lead to early thinning in the central fovea as well as the
      parafoveal regions that is detected by SD-OCT. 

PMID- 26301101
TI  - Gastrointestinal problems in modern wars: clinical features and possible
      mechanisms.
AB  - Gastrointestinal problems are common during wars, and they have exerted
      significant adverse effects on the health of service members involved in warfare.
      The spectrum of digestive diseases has varied during wars of different eras. At
      the end of the 20th century, new frontiers of military medical research emerged
      due to the occurrence of high-tech wars such as the Gulf War and the Kosovo War,
      in which ground combat was no longer the primary method of field operations. The
      risk to the military personnel who face trauma has been greatly reduced, but
      disease and non-battle injuries (DNBIs) such as neuropsychological disorders and
      digestive diseases seemed to be increased. Data revealed that gastrointestinal
      symptoms such as constipation, diarrhea, dyspepsia, and noncardiac chest pain are
      common among military personnel during modern wars. In addition, a large number
      of deployed soldiers and veterans who participated in recent wars presented with
      chronic gastrointestinal complaints, which fulfilled with the Rome III criteria
      for functional gastrointestinal disorders (FGIDs). It was also noted that many
      veterans who returned from the Gulf War suffered not only from chronic digestive
      symptoms but also from neuropsychological dysfunction; however, they also showed
      symptoms of other systems. Presently, this broad range of unexplained symptoms is
      known as "Gulf War syndrome". The mechanism that underlies Gulf War syndrome
      remains unclear, but many factors have been associated with this syndrome such as
      war trauma, stress, infections, immune dysfunction, radiological factors, anthrax
      vaccination and so on. Some have questioned if the diagnosis of FGIDs can be
      reached given the complexity of the military situation. As a result, further
      studies are needed to elucidate the pathogenesis of gastrointestinal disease
      among military personnel. 

PMID- 26301103
TI  - Correlation between Retinal Changes and Visual Function in Late-Stage Vogt
      Koyanagi-Harada Disease: An Optical Coherence Tomography Study.
AB  - Purpose. To characterize the optical coherence tomography (OCT) findings in late
      stage Vogt-Koyanagi-Harada (VKH) disease and its correlation with visual
      function. Methods. The records of patients with late-stage VKH disease (defined
      as >=12 months from disease onset) were retrospectively reviewed. The analysis
      focused on the OCT findings and microperimetry, in addition to the possible
      correlation between morphology and functional findings. Results. Twenty-nine
      patients (58 eyes) were included. Mean age at onset was 34.24 +/- 10.67 years.
      The OCT revealed that the outer retina and retinal pigment epithelium (RPE) were
      mainly affected. These effects included RPE thickening and breakage or
      disappearance of the cone outer segment tip (COST) line and/or inner
      segment/outer segment (IS/OS) junction. The COST line and IS/OS results were
      related to macular function and the interval between symptom onset and initiation
      of high-dose corticosteroid treatment (all P < 0.01). Eyes with intact COST lines
      demonstrated intact IS/OS and normal RPE layers as well as better visual function
      and normal retinal sensitivity. Conclusions. The OCT findings are strongly
      correlated with macular function, as well as other clinical findings in late
      stage VKH. With respect to the COST line and retinal sensitivity especially, the
      OCT and microperimetry findings may be useful for evaluating later-stage VKH. 

PMID- 26301104
TI  - Clinical Outcomes after Binocular Implantation of a New Trifocal Diffractive
      Intraocular Lens.
AB  - Purpose. To evaluate visual, refractive, and contrast sensitivity outcomes, as
      well as the incidence of pseudophakic photic phenomena and patient satisfaction
      after bilateral diffractive trifocal intraocular lens (IOL) implantation.
      Methods. This prospective nonrandomized study included consecutive patients
      undergoing cataract surgery with bilateral implantation of a diffractive trifocal
      IOL (AT LISA tri 839MP, Carl Zeiss Meditec). Distance, intermediate, and near
      visual outcomes were evaluated as well as the defocus curve and the refractive
      outcomes 3 months after surgery. Photopic and mesopic contrast sensitivity,
      patient satisfaction, and halo perception were also evaluated. Results. Seventy
      six eyes of 38 patients were included; 90% of eyes showed a spherical equivalent
      within +/-0.50 diopters 3 months after surgery. All patients had a binocular
      uncorrected distance visual acuity of 0.00 LogMAR or better and a binocular
      uncorrected intermediate visual acuity of 0.10 LogMAR or better, 3 months after
      surgery. Furthermore, 85% of patients achieved a binocular uncorrected near
      visual acuity of 0.10 LogMAR or better. Conclusions. Trifocal diffractive IOL
      implantation seems to provide an effective restoration of visual function for
      far, intermediate, and near distances, providing high levels of visual quality
      and patient satisfaction. 

PMID- 26301105
TI  - Lung Injury Prediction Score Is Useful in Predicting Acute Respiratory Distress
      Syndrome and Mortality in Surgical Critical Care Patients.
AB  - Background. Lung injury prediction score (LIPS) is valuable for early recognition
      of ventilated patients at high risk for developing acute respiratory distress
      syndrome (ARDS). This study analyzes the value of LIPS in predicting ARDS and
      mortality among ventilated surgical patients. Methods. IRB approved, prospective
      observational study including all ventilated patients admitted to the surgical
      intensive care unit at a single tertiary center over 6 months. ARDS was defined
      using the Berlin criteria. LIPS were calculated for all patients and analyzed.
      Logistic regression models evaluated the ability of LIPS to predict development
      of ARDS and mortality. A receiver operator characteristic (ROC) curve
      demonstrated the optimal LIPS value to statistically predict development of ARDS.
      Results. 268 ventilated patients were observed; 141 developed ARDS and 127 did
      not. The average LIPS for patients who developed ARDS was 8.8 +/- 2.8 versus 5.4
      +/- 2.8 for those who did not (p < 0.001). An ROC area under the curve of 0.79
      demonstrates LIPS is statistically powerful for predicting ARDS development.
      Furthermore, for every 1-unit increase in LIPS, the odds of developing ARDS
      increase by 1.50 (p < 0.001) and odds of ICU mortality increase by 1.22 (p <
      0.001). Conclusion. LIPS is reliable for predicting development of ARDS and
      predicting mortality in critically ill surgical patients. 

PMID- 26301106
TI  - Intraoperative Myelography in Cervical Multilevel Stenosis Using 3D Rotational
      Fluoroscopy: Assessment of Feasibility and Image Quality.
AB  - Background. Intraoperative myelography has been reported for decompression
      control in multilevel lumbar disease. Cervical myelography is technically more
      challenging. Modern 3D fluoroscopy may provide a new opportunity supplying
      multiplanar images. This study was performed to determine the feasibility and
      image quality of intraoperative cervical myelography using a 3D fluoroscope.
      Methods. The series included 9 patients with multilevel cervical stenosis. After
      decompression, 10 mL of water-soluble contrast agent was administered via a
      lumbar drainage and the operating table was tilted. Thereafter, a 3D fluoroscopy
      scan (O-Arm) was performed and visually evaluated. Findings. The quality of
      multiplanar images was sufficient to supply information about the presence of
      residual stenosis. After instrumentation, metal artifacts lowered image quality.
      In 3 cases, decompression was continued because myelography depicted residual
      stenosis. In one case, anterior corpectomy was not completed because myelography
      showed sufficient decompression after 2-level discectomy. Interpretation.
      Intraoperative myelography using 3D rotational fluoroscopy is useful for the
      control of surgical decompression in multilevel spinal stenosis providing images
      comparable to postmyelographic CT. The long duration of contrast delivery into
      the cervical spine may be solved by preoperative contrast administration. The
      method is susceptible to metal artifacts and, therefore, should be applied before
      metal implants are placed. 

PMID- 26301108
TI  - Melanonychia Secondary to Long-Term Treatment with Hydroxycarbamide: An Essential
      Thrombocytosis Case.
AB  - Hydroxycarbamide is used in the treatment of essential thrombocytosis and other
      myeloproliferative disorders. We report the case of a 63-year-old woman with
      essential thrombocytosis who had melanonychia after the long-term use of the
      hydroxycarbamide with a dose of 1000 mg/day. Two years after the initiation of
      the hydroxycarbamide, our patient had pain on her toes and melanonychia on her
      nails. Hydroxycarbamide treatment was discontinued because of pain and she was
      given anagrelide treatment. The pathogenesis of melanonychia secondary to long
      term hydroxycarbamide treatment is not yet well understood. Some investigators
      suggested that genetic factors, induction of melanocytes, and some changes in
      nail matrix could be the reason of hydroxycarbamide related melanonychia. Our
      patient has suffered color changes in her nails as well as pain that made us
      doubtful for a beginning of ulceration besides melanonychia. Maybe early clinical
      reaction of discontinuation of the drug has prevented more severe side effect
      like ulceration in our patient. Also side effect of hydroxycarbamide has
      developed more slowly in our patient compared to other patients in the mentioned
      study. To conclude, long-term hydroxycarbamide treatment can cause mucocutaneous
      side effects and more studies should be done in future in order to reveal the
      underlying mechanism. 

PMID- 26301107
TI  - Complex Inflammation mRNA-Related Response in ALS Is Region Dependent.
AB  - Inflammatory changes are analyzed in the anterior spinal cord and frontal cortex
      area 8 in typical spinal-predominant ALS cases. Increased numbers of astrocytes
      and activated microglia are found in the anterior horn of the spinal cord and
      pyramidal tracts. Significant increased expression of TLR7, CTSS, and CTSC mRNA
      and a trend to increased expression of IL10RA, TGFB1, and TGFB2 are found in the
      anterior lumbar spinal cord in ALS cases compared to control cases, whereas
      C1QTNF7 and TNFRSF1A mRNA expression levels are significantly decreased. IL6 is
      significantly upregulated and IL1B shows a nonsignificant increased expression in
      frontal cortex area 8 in ALS cases. IL-6 immunoreactivity is found in scattered
      monocyte-derived macrophages/microglia and TNF-alpha in a few cells of unknown
      origin in ALS cases. Increased expression and abnormal distribution of IL-1beta
      occurred in motor neurons of the lumbar spinal cord in ALS. Strong IL-10
      immunoreactivity colocalizes with TDP-43-positive inclusions in motor neurons in
      ALS cases. The present observations show a complex participation of cytokines and
      mediators of the inflammatory response in ALS consistent with increased
      proinflammatory cytokines and sequestration of anti-inflammatory IL-10 in
      affected neurons. 

PMID- 26301109
TI  - Unexpected Abscess Localization of the Anterior Abdominal Wall in an ADPKD
      Patient Undergoing Hemodialysis.
AB  - Autosomal Dominant Polycystic Kidney Disease (ADPKD) is one of the most common
      monogenic disorders and the leading inheritable cause of end-stage renal disease
      worldwide. Cystic and noncystic extrarenal manifestations are correlated with
      variable clinical presentations so that an inherited disorder is now considered a
      systemic disease. Kidney and liver cystic infections are the most common
      infectious complications in ADPKD patients. Furthermore, it is well known that
      ADPKD is commonly associated with colonic diverticular disease which recently has
      been reported to be linked to increased risk of infection on hemodialysis
      patients. Herein, we present a case of anterior abdominal wall abscess caused by
      Enterococcus faecalis in a patient with ADPKD undergoing hemodialysis. Although
      the precise pathway of infection remains uncertain, the previous medical history
      as well as the clinical course of our patient led us to hypothesize an
      alternative route of infection from the gastrointestinal tract through an
      aberrant intestinal barrier into the bloodstream and eventually to an atypical
      location. 

PMID- 26301110
TI  - Pediatric Papillary Renal Cell Carcinoma in a Horseshoe Kidney: A Case Report
      with Review of the Literature.
AB  - Renal cell carcinoma is the most common malignancy of the kidney in adults. In
      children, however, it only accounts for an estimated 1.8 to 6.3% of all pediatric
      malignant renal tumors. Papillary renal cell carcinoma is the second most common
      type of renal cell carcinoma in children. We present the case of a 12-year-old
      boy with a 2-month history of abdominal pain, unexplained weight loss, and gross
      hematuria. Computed tomography revealed a horseshoe kidney and a well-defined
      mass of 4 cm arising from the lower pole of the right kidney. Microscopically the
      tumor was composed of papillae covered with cells with abundant eosinophilic
      cytoplasm and high-grade nuclei with prominent nucleoli. Immunohistochemistry was
      performed; EMA, Vimentin, and AMACR were strongly positive while CK7, CD10, RCC
      antigen, TFE3, HMB-45, and WT-1 were negative. Currently, 10 months after the
      surgical procedure, the patient remains clinically and radiologically disease
      free. 

PMID- 26301111
TI  - Novel Technique for Management of Axillary Hidradenitis Suppurativa Using Setons.
AB  - Management of hidradenitis suppurativa (HS) of the axilla which is nonresponding
      to conservative management presents a significant therapeutic challenge. Most
      surgical treatment options are associated with significant morbidities and
      prolonged hospital stay. We present a technique of management of HS using setons
      which is simple and allows the ongoing treatment to be done on an outpatient
      basis. Given the fact that HS is a chronic relapsing condition each recurrence
      may again be managed using this technique. This will allow the patients to manage
      their recurrences with minimal impact on their activities of daily living. 

PMID- 26301112
TI  - Massive Neurilemoma of the Hard Plate in Which Preoperative Diagnosis Was
      Difficult.
AB  - The patient was an 84-year-old man who was referred to our hospital in mid
      December 2012 for a close examination of a mass arising from the left side of the
      hard palate that was found by a local dentist. The initial examination revealed
      the presence of a 3.0-cm elastic soft, dome-shaped mass in the left hard palate.
      CE-CT showed a lesion of size 1.8 * 1.4 cm in the right hard palate, which
      extended upward and invaded the nasal cavity. The mass was a solid tumor
      associated with resorption of surrounding bone and expansion of the greater
      palatine canal. CE-MRI indicated that the mass extended upward and invaded the
      nasal cavity, and the mass showed hypointensity on T1-weighted images,
      hyperintensity on T2-weighted images, and an irregular margin with internal
      enhancement. Abnormal uptake of FDG on PET-CT (SUVmax = 5.2) was observed in the
      left hard palate. The biopsy site lesion rapidly increased in size and biopsy was
      performed again in January 2013 due to suspicion of a malignant tumor. The
      histopathological diagnosis was a suspected malignant neurogenic tumor.
      Therefore, the patient underwent partial maxillectomy and a split-thickness skin
      graft in late February 2013. No recurrence was noted 29 months after the
      operation. 

PMID- 26301113
TI  - Thoracic Kidney: Extremely Rare State of Aberrant Kidney.
AB  - The thorax is the rarest place among all forms of renal ectopia. We report a rare
      case of an unacquired thoracic kidney. Only about 200 cases of the thoracic
      kidney have ever been reported in medical literature worldwide. In this paper we
      present the rarest form of nontraumatic nonhernia associated, truly ectopic
      thoracic kidney. The differential diagnosis and management options and
      classification of this rare form of aberrant kidney are discussed. 

PMID- 26301114
TI  - Prevalence of Plasmid-Mediated Quinolone Resistance Determinants and OqxAB Efflux
      Pumps among Extended-Spectrum beta-Lactamase Producing Klebsiella pneumoniae
      Isolated from Patients with Nosocomial Urinary Tract Infection in Tehran, Iran.
AB  - Objective. Plasmid-mediated quinolone resistance (PMQR) plays an important role
      in the development of clinical resistance to quinolone. The aim of this study was
      to investigate PMQR determinants among extended-spectrum beta-lactamases- (ESBL-)
      producing Klebsiella pneumoniae recovered from patients with nosocomial urinary
      tract infection (UTI). Methods. A total of 247 ESBL-producing K. pneumoniae
      isolates were collected from 750 patients with UTI. ESBL production was confirmed
      by double disc synergy test and combined disc diffusion test. The prevalence of
      PMQR determinants among ESBL-producing K. pneumoniae was assessed using PCR
      method. Results. The rates of resistance to antimicrobial agents in present study
      varied from 14.2% to 98.8%. In comparison with other PMQR genotypes, the
      frequency of aac(6')-Ib (68.8%) was strikingly high. Of the 247 isolates tested,
      qnrA, qnrB, qnrS, and qepA genes were present in 3.6%, 1.6%, 1.2, and 2%,
      respectively. oqxA and oqxB were detected in 56.7% and 54.6% of isolates. The
      predominant coexisting ESBL and PMQR profile among our isolates included bla CTX
      M and aac(6')-Ib, oqxA, oqxB (28.3%) and bla TEM, bla SHV and aac(6')-Ib, oqxA,
      and oqxB (19.4%) profile.  Conclusion. Given the linkage observed between
      resistance to quinolones and beta lactam antibiotics, therapeutic protocol with
      fluoroquinolones and beta lactam antibiotics should be seriously revised in
      Tehran hospitals. 

PMID- 26301115
TI  - Assessment of Vascular Endothelial Growth Factor in Fresh versus Frozen Platelet
      Rich Plasma.
AB  - Platelet rich plasma (PRP) is hemoconcentration with platelets concentration
      above baseline values and high concentration of many growth factors. The aim of
      this study was to assess freezing effect on vascular endothelial growth factor
      (VEGF) release from PRP using two different activation methods to simplify its
      use in different clinical applications. PRP was prepared using two-centrifugation
      steps method from 12 qualified blood donors. VEGF concentrations were measured in
      fresh PRP and after freezing/thawing for one and three weeks with two methods of
      activation using (i) calcium gluconate and (ii) calcium gluconate and thrombin.
      Platelets count was significantly increased compared to baseline whole blood
      values in all fresh and frozen PRP samples (p value was <0.05). No significant
      difference was found between VEGF concentrations after activating fresh and
      frozen-thawed PRP samples for one and three weeks by calcium alone or calcium
      with thrombin, and also no significant difference was found when freezing period
      was extended from one to three weeks. Our results showed that platelets count
      does not correlate with variable levels of VEGF. PRP could be prepared once and
      preserved frozen for at least three weeks for the next treatment sessions and
      activation with thrombin addition to calcium will not augment the growth factor
      release. 

PMID- 26301116
TI  - Keeping it simple: the value of an irreducibly simple climate model.
AB  - Richardson et al. (Sci Bull, 2015. doi:10.1007/s11434-015-0806-z) suggest that
      the irreducibly simple climate model described in Monckton of Brenchley et al.
      (Sci Bull 60:122-135, 2015. doi:10.1007/s11434-014-0699-2) was not validated
      against observations, relying instead on synthetic test data based on
      underestimated global warming, illogical parameter choice and near-instantaneous
      response at odds with ocean warming and other observations. However, the simple
      model, informed by its authors' choice of parameters, usually hindcasts observed
      temperature change more closely than the general-circulation models, and finds
      high climate sensitivity implausible. With IPCC's choice of parameters, the model
      is further validated in that it duly replicates IPCC's sensitivity interval.
      Also, fast climate system response is consistent with near-zero or net-negative
      temperature feedback. Given the large uncertainties in the initial conditions and
      evolutionary processes determinative of climate sensitivity, subject to obvious
      caveats a simple sensitivity-focused model need not, and the present model does
      not, exhibit significantly less predictive skill than the general-circulation
      models.

PMID- 26301117
TI  - Emerging roles of myeloid derived suppressor cells in hepatic inflammation and
      fibrosis.
AB  - Myeloid derived suppressor cells (MDSC) are a heterogeneous population of immune
      cells that are potent suppressors of immune responses. MDSC emerge in various
      compartments in the body, such as blood, bone marrow or spleen, especially in
      conditions of cancer, infections or inflammation. MDSC usually express CD11b,
      CD33, and low levels of human leukocyte antigen-DR in humans or CD11b and Gr1
      (Ly6C/G) in mice, and they can be further divided into granulocytic or monocytic
      MDSC. The liver is an important organ for MDSC induction and accumulation in
      hepatic as well as extrahepatic diseases. Different hepatic cells, especially
      hepatic stellate cells, as well as liver-derived soluble factors, including
      hepatocyte growth factor and acute phase proteins (SAA, KC), can promote the
      differentiation of MDSC from myeloid cells. Importantly, hepatic myeloid cells
      like neutrophils, monocytes and macrophages fulfill essential roles in acute and
      chronic liver diseases. Recent data from patients with liver diseases and animal
      models linked MDSC to the pathogenesis of hepatic inflammation, fibrosis and
      hepatocellular carcinoma (HCC). In settings of acute hepatitis, MDSC can limit
      immunogenic T cell responses and subsequent tissue injury. In patients with
      chronic hepatitis C, MDSC increase and may favor viral persistence. Animal models
      of chronic liver injury, however, have not yet conclusively clarified the
      involvement of MDSC for hepatic fibrosis. In human HCC and mouse models of liver
      cancer, MDSC are induced in the tumor environment and suppress anti-tumoral
      immune responses. Thus, the liver is a primary site of MDSC in vivo, and
      modulating MDSC functionality might represent a promising novel therapeutic
      target for liver diseases. 

PMID- 26301119
TI  - Can high resolution manometry parameters for achalasia be obtained by
      conventional manometry?
AB  - High resolution manometry (HRM) is a new technology that made important
      contributions to the field of gastrointestinal physiology. HRM showed clear
      advantages over conventional manometry and it allowed the creation of different
      manometric parameters. On the other side, conventional manometry is still wild
      available. It must be better studied if the new technology made possible the
      creation and study of these parameters or if they were always there but the
      colorful intuitive panoramic view of the peristalsis from the pharynx to the
      stomach HRM allowed the human eyes to distinguish subtle parameters unknown or
      uncomprehend so far and if HRM parameters can be reliably obtained by
      conventional manometry and data from conventional manometry still can be accepted
      in achalasia studies. Conventional manometry relied solely on the residual
      pressure to evaluate lower esophageal sphincter (LES) relaxation while HRM can
      obtain the Integrated Relaxation Pressure. Esophageal body HRM parameters defines
      achalasia subtypes, the Chicago classification, based on esophageal
      pressurization after swallows. The characterization of each subtype is very
      intuitive by HRM but also easy by conventional manometry since only wave
      amplitudes need to be measured. In conclusion, conventional manometry is still
      valuable to classify achalasia according to the Chicago classification. HRM
      permits a better study of the LES. 

PMID- 26301118
TI  - Gut region-dependent alterations of nitrergic myenteric neurons after chronic
      alcohol consumption.
AB  - Chronic alcohol abuse damages nearly every organ in the body. The harmful effects
      of ethanol on the brain, the liver and the pancreas are well documented. Although
      chronic alcohol consumption causes serious impairments also in the
      gastrointestinal tract like altered motility, mucosal damage, impaired absorption
      of nutrients and inflammation, the effects of chronically consumed ethanol on the
      enteric nervous system are less detailed. While the nitrergic myenteric neurons
      play an essential role in the regulation of gastrointestinal peristalsis, it was
      hypothesised, that these neurons are the first targets of consumed ethanol or its
      metabolites generated in the different gastrointestinal segments. To reinforce
      this hypothesis the effects of ethanol on the gastrointestinal tract was
      investigated in different rodent models with quantitative immunohistochemistry,
      in vivo and in vitro motility measurements, western blot analysis, evaluation of
      nitric oxide synthase enzyme activity and bio-imaging of nitric oxide synthesis.
      These results suggest that chronic alcohol consumption did not result significant
      neural loss, but primarily impaired the nitrergic pathways in gut region
      dependent way leading to disturbed gastrointestinal motility. The gut segment
      specific differences in the effects of chronic alcohol consumption highlight the
      significance the ethanol-induced neuronal microenvironment involving oxidative
      stress and intestinal microbiota. 

PMID- 26301120
TI  - Iron deficiency anemia in inflammatory bowel disease.
AB  - Anemia is a common extraintestinal manifestation of inflammatory bowel disease
      (IBD) and is frequently overlooked as a complication. Patients with IBD are
      commonly found to have iron deficiency anemia (IDA) secondary to chronic blood
      loss, and impaired iron absorption due to tissue inflammation. Patients with iron
      deficiency may not always manifest with signs and symptoms; so, hemoglobin levels
      in patients with IBD must be regularly monitored for earlier detection of anemia.
      IDA in IBD is associated with poor quality of life, necessitating prompt
      diagnosis and appropriate treatment. IDA is often associated with inflammation in
      patients with IBD. Thus, commonly used laboratory parameters are inadequate to
      diagnose IDA, and newer iron indices, such as reticulocyte hemoglobin content or
      percentage of hypochromic red cells or zinc protoporphyrin, are required to
      differentiate IDA from anemia of chronic disease. Oral iron preparations are
      available and are used in patients with mild disease activity. These preparations
      are inexpensive and convenient, but can produce gastrointestinal side effects,
      such as abdominal pain and diarrhea, that limit their use and patient compliance.
      These preparations are partly absorbed due to inflammation. Non-absorbed iron can
      be toxic and worsen IBD disease activity. Although cost-effective intravenous
      iron formulations are widely available and have improved safety profiles,
      physicians are reluctant to use them. We present a review of the pathophysiologic
      mechanisms of IDA in IBD, improved diagnostic and therapeutic strategies,
      efficacy, and safety of iron replacement in IBD. 

PMID- 26301121
TI  - Designer probiotics: Development and applications in gastrointestinal health.
AB  - Given the increasing commercial and clinical relevance of probiotics, improving
      their stress tolerance profile and ability to overcome the physiochemical
      defences of the host is an important biological goal. Herein, I review the
      current state of the art in the design of engineered probiotic cultures, with a
      specific focus on their utility as therapeutics for the developing world; from
      the treatment of chronic and acute enteric infections, and their associated
      diarrhoeal complexes, to targeting HIV and application as novel mucosal vaccine
      delivery vehicles. 

PMID- 26301122
TI  - Human microbiome: From the bathroom to the bedside.
AB  - The human gut contains trillions of bacteria, the major phylae of which include
      Bacteroidetes, Firmicutes, Actinobacteria and Proteobacteria. Fecal microbial
      transplantation (FMT) has been known of for many years but only recently has been
      subjected to rigorous examination. We review the evidence regarding FMT for
      recurrent Clostridium difficile infection which has resulted in it being an
      approved treatment. In addition there is some evidence for its use in both
      irritable bowel syndrome and inflammatory bowel disease. Further research is
      needed in order to define the indications for FMT and the most appropriate method
      of administration. 

PMID- 26301123
TI  - Neuronal spike-train responses in the presence of threshold noise.
AB  - The variability of neuronal firing has been an intense topic of study for many
      years. From a modelling perspective it has often been studied in conductance
      based spiking models with the use of additive or multiplicative noise terms to
      represent channel fluctuations or the stochastic nature of neurotransmitter
      release. Here we propose an alternative approach using a simple leaky integrate
      and-fire model with a noisy threshold. Initially, we develop a mathematical
      treatment of the neuronal response to periodic forcing using tools from linear
      response theory and use this to highlight how a noisy threshold can enhance
      downstream signal reconstruction. We further develop a more general framework for
      understanding the responses to large amplitude forcing based on a calculation of
      first passage times. This is ideally suited to understanding stochastic mode
      locking, for which we numerically determine the Arnol'd tongue structure. An
      examination of data from regularly firing stellate neurons within the ventral
      cochlear nucleus, responding to sinusoidally amplitude modulated pure tones,
      shows tongue structures consistent with these predictions and highlights that
      stochastic, as opposed to deterministic, mode-locking is utilised at the level of
      the single stellate cell to faithfully encode periodic stimuli.

PMID- 26301124
TI  - Challenges Presented by Re-Emerging Sexually Transmitted Infections in HIV
      Positive Men who have Sex with Men: An Observational Study of Lymphogranuloma
      Venereum in the UK.
AB  - BACKGROUND: United Kingdom has reported the largest documented outbreak of
      lymphogranuloma venereum (LGV), a re-emerging sexually transmitted infection
      (STI) which is primarily seen in HIV-positive men who have sex with men (MSM). A
      diagnostic service was established in response to the outbreak linked to a
      voluntary LGV Enhanced Surveillance system. We examined the performance of this
      novel surveillance system to identify utility in tracking a re-emerging
      infection. METHODS: We described laboratory data on samples and surveillance data
      from case reports for LGV from 2004-2010. We performed a cross-sectional analysis
      comparing clinical and behavioural characteristics of HIV-positive and HIV
      negative/unknown LGV cases diagnosed in MSM using multivariable logistic
      regression models with generalised estimating equations to control for repeat
      infections. RESULTS: LGV Surveillance data were available for 87% (1,370/1,581)
      of LGV cases (after de-duplication). There were 1,342 episodes in 1,281 MSM, most
      of whom were known to be HIV-positive (1,028/1,281, 80.2%,). HIV-positive men
      reported a shorter duration of symptoms (aOR 0.5; 95%CI 0.3, 0.8 for reporting
      more than a week compared to a week or less) in comparison to HIV
      negative/unknown MSM, and were more likely to report unprotected receptive anal
      intercourse (aOR 2.7; 95% CI 1.3, 5.8). CONCLUSION: The surveillance identified
      the population at greater risk of infection based on higher levels of risk
      behaviour in HIV-positive LGV cases. However, there was diagnostic bias towards
      HIV-positive LGV cases who presented with a shorter duration of symptoms when
      compared to HIV-negative/unknown LGV cases.

PMID- 26301125
TI  - Assesment of Conjunctival Microangiopathy in a Patient with Diabetes Mellitus
      Using the Retinal Function Imager.
AB  - Diabetes mellitus (DM) is notorious for causing retinal microangiopathy, but
      bulbar conjunctival microangiopathy (CM) mirroring the established retinal vessel
      changes, has also been observed. Recent studies suggest that CM occurs in all DM
      patients in various degrees depending on disease severity and occur even before
      non-proliferative retinopathy develops. Thus, CM might provide a means of early
      detection or even form a basis for early intervention of disease progression in
      DM patients. Herein we present - to our knowledge for the first time-the
      feasibility and applicability in diagnostic imaging of CM in a diabetic patient
      using a commercially available Retinal Function Imager (RFI, Optical Imaging Ltd,
      Rehovot, Israel).

PMID- 26301127
TI  - Submitting for Dollars: Playing the Funding Game to Promote Transcultural
      Nursing.
AB  - Research requires funding! Every researcher understands the crucial role that
      money plays in implementing a research study. Research for nursing is no
      different. In the current economic environment, funding sources have become
      limited. Therefore, researchers need to be prepared to submit grant proposals
      which will give them a competitive edge over other proposals. This paper will:
      (1) describe the development of a grant proposal for National Institutes of
      Health funding, and (2) provide suggestions to novice researchers about how to
      write a proposal that has the potential to receive a fundable score. This team of
      early stage investigators submitted a proposal which received a fundable score,
      but was not selected for funding. The proposal was revised, re-submitted, and
      received a highly competitive score that did result in funding. The lessons
      learned from this process can be useful for other nurses seeking to secure
      funding for their research projects.

PMID- 26301126
TI  - Immunology of Corneal Allografts: Insights from Animal Models.
AB  - Corneal transplantation stands alone as the most common and successful form of
      solid organ transplantation. Even though HLA matching and systemic antirejection
      drugs are not routinely used, 90% of the first time corneal allografts will
      succeed. By contrast, all other major categories of organ transplantation require
      HLA matching and the use of systemically administered immunosuppressive drugs.
      This remarkable success of corneal transplants under these conditions is an
      example of "immune privilege" and is the primary reason for the extraordinary
      success of corneal transplantation. A number of dogmas have emerged over the past
      century to explain immune privilege and the immunobiology of corneal
      transplantation. Many of these dogmas have been based largely on inferences from
      clinical observations on keratoplasty patients. The past 30 years have witnessed
      a wealth of rodent studies on corneal transplantation that have tested hypotheses
      and dogmas that originated from clinical observations on penetrating keratoplasty
      patients. Rodent models allow the application of highly sophisticated genetic and
      immunological tools for testing these hypotheses in a controlled environment and
      with experiments designed prospectively. These studies have validated some of the
      widely held assumptions based on clinical observations and in other cases,
      previous dogmas have been replaced with new insights that could only come from
      prospective studies performed under highly controlled conditions. This review
      highlights some of the key dogmas and these widely held assumptions that have
      been scrutinized through the use of rodent models of penetrating keratoplasty.
      This review also makes note of new immunological principles of corneal immunology
      that have emerged from rodent studies on corneal transplantation that most likely
      would not have been revealed in studies on corneal transplantation patients.

PMID- 26301128
TI  - Challenges Faced by Village Health Teams (VHTs) in Amuru, Gulu and Pader
      Districts in Northern Uganda.
AB  - Primary health care provision through innovative community level interventions
      such as the Village Health Team (VHT) concept in Uganda can be a rational way of
      achieving universal access to healthcare. This cross-sectional study interviewed
      150 VHT members and 16 key informants in three districts in Northern Uganda to
      establish the roles of VHTs, the service gaps encountered and the measures in
      place to address these gaps. Quantitative data were analyzed using SPSS 16.0.
      Direct content analysis of themes of transcribed qualitative data was conducted
      manually for common codes. The majority of the respondents 64.29% (n = 72)
      reported to have been VHT volunteers for more than 5 years. Among the roles were
      community mobilization reported by 99.1% (n = 111) and home visiting of
      individuals reported by 97.3% (n = 109). Lack of transport, motivation, adequate
      skills and community appreciation with nearly no measures in place to counteract
      the challenges was reported by almost all respondents. Although the VHT concept
      can be a significant means of achieving universal access to primary health care,
      extensive community involvement and motivation of the volunteers are highly
      needed for a maximum benefit.

PMID- 26301129
TI  - Surgical Excision with Adjuvant Irradiation for Treatment of Keloid Scars: A
      Systematic Review.
AB  - BACKGROUND: Excision followed by adjuvant irradiation is considered safe and most
      efficacious for treatment of keloid scars. Recently, different authors published
      successful treatment protocols and recommended the following: (1) the use of high
      dose-rate brachytherapy instead of low-dose-rate brachytherapy or external
      radiation; (2) a short-time interval between operation and irradiation; (3)
      single fraction instead of multifraction irradiation; and (4) a minimum of 12- to
      24-month follow-up post treatment. METHODS: This study evaluates the above
      recommendations with a systematic review of the English-language literature,
      based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis
      statement. Both PubMed and EMBASE were searched. Studies were graded according to
      the American Society of Plastic Surgeons Rating Levels of Evidence. RESULTS:
      Thirty-three studies were selected. Six studies were graded as level of evidence
      type II studies and 27 as type III. High-dose-rate brachytherapy showed lower
      recurrence rates compared with low-dose-rate brachytherapy and external
      radiation. A short-time (<7 hours) interval between scar excision and irradiation
      results in a lower recurrence rate compared with long-time intervals (>24 hours).
      Single-fraction irradiation showed promising results in terms of recurrence rate
      and patient convenience. Finally, scar recurrences were seen between 2 and 36
      months, with a mean of 15 months. CONCLUSIONS: Based on this systematic review of
      the literature, the evidence confirms the recommendations stated by authors in
      the recent years. However, due to the lack of high-quality randomized studies,
      the quality of this evidence is limited. More randomized studies will generate
      stronger recommendations.

PMID- 26301130
TI  - Evaluation of Lipofilling Safety in Elderly Patients with Breast Cancer.
AB  - BACKGROUND: Lipofilling is widely used in breast reconstruction after mastectomy
      with reconstruction or breast conserving surgery in patients with breast cancer.
      The aim of this study is focused on complications associated with lipofilling in
      elderly breast cancer patients with breast defects after breast conserving
      surgery or reconstruction. METHODS: A total of 137 patients older than 60 years
      who underwent 153 lipofilling procedures were included. All patients had
      undergone breast lipofilling using Coleman's technique. Estimated breast defect
      volume, lipofilling volume, and complications after lipofilling were obtained for
      analysis. RESULTS: Most patients (67%) had only 1 lipofilling procedure. The
      median lipofilling volume to breast defect volume ratio was 1.5. No severe
      complications were found after treatment. Liponecrosis was detected in 10 of 153
      breasts (7%) or 9 of 137 patients within 2 weeks after lipofilling and required
      surgical drainage in 2. No local recurrences were noted. CONCLUSIONS: The
      incidence of liponecrosis after lipofilling in elderly patients was relatively
      high, requiring surgical drainage in some cases. As a rough guide, the
      lipofilling volume should not exceed 1.5 times the defect volume, and close
      postoperative follow-up within the first 2 weeks is suggested for these patients.

PMID- 26301131
TI  - The Americleft Project: Burden of Care from Secondary Surgery.
AB  - BACKGROUND: The burden of care for children with cleft lip and palate extends
      beyond primary repair. Children may undergo multiple secondary surgeries to
      improve appearance or speech. The purpose of this study was to compare the use of
      secondary surgery between cleft centers. METHODS: This retrospective cohort study
      included 130 children with complete unilateral cleft lip and palate treated
      consecutively at 4 cleft centers in North America. Data were collected on all
      lip, palate, and nasal surgeries. Nasolabial appearance was rated by a panel of
      judges using the Asher-McDade scale. Risk of secondary surgery was compared
      between centers using the log-rank test, and hazard ratios estimated with a Cox
      proportional hazards model. RESULTS: Median follow-up was 18 years (interquartile
      range, 15-19). There were significant differences among centers in the risks of
      secondary lip surgery (P < 0.001) and secondary rhinoplasty (P < 0.001). The
      cumulative risk of secondary lip surgery by 10 years of age ranged from 5% to 60%
      among centers. The cumulative risk of secondary rhinoplasty by 20 years of age
      ranged from 47% to 79% among centers. No significant differences in nasolabial
      appearance were found between children who underwent secondary lip or nasal
      surgery and children who underwent only primary surgery (P > 0.10). CONCLUSIONS:
      Although some cleft centers were significantly more likely to perform secondary
      surgery, the use of secondary surgery did not achieve significantly better
      nasolabial appearance than what was achieved by children who underwent only
      primary surgery.

PMID- 26301132
TI  - Three-dimensional Printing in Developing Countries.
AB  - The advent of 3-dimensional (3D) printing technology has facilitated the creation
      of customized objects. The lack of regulation in developing countries renders
      conventional means of addressing various healthcare issues challenging. 3D
      printing may provide a venue for addressing many of these concerns in an
      inexpensive and easily accessible fashion. These may potentially include the
      production of basic medical supplies, vaccination beads, laboratory equipment,
      and prosthetic limbs. As this technology continues to improve and prices are
      reduced, 3D printing has the potential ability to promote initiatives across the
      entire developing world, resulting in improved surgical care and providing a
      higher quality of healthcare to its residents. 

PMID- 26301133
TI  - Suprascapular Nerve Partial Section by the Transverse Scapular Ligament: One
      Case.
AB  - We present a case of suprascapular nerve idiopathic total palsy lasting for 2
      years, with intraoperative finding of suprascapular nerve partial section by the
      superior transverse scapular ligament. This highlights the importance of early
      surgical management with an open procedure for suprascapular neuropathy of
      unknown etiology. 

PMID- 26301134
TI  - Unusual Dermatological Manifestations of Gout: Review of Literature and a Case
      Report.
AB  - BACKGROUND: Gouty panniculitis is a rare clinical manifestation of gout,
      characterized by deposits of monosodium urate crystals in the hypodermis. Our aim
      was to describe atypical and rare clinical presentations of gouty tophi. METHODS:
      We searched relevant English and Spanish literature of unusual gout
      manifestations using the following keywords: giant, gout, panniculitis, gouty
      panniculitis, gouty tophi, rare manifestations of gout, gouty, tophi, tophus,
      monosodium urate, uric acid, and unusual. Well-described case reports, case
      series, and review articles were evaluated and included in the literature review.
      RESULTS: International literature has reported fewer than 10 cases of gouty
      panniculitis worldwide. In this case report, the patient presents a rare
      manifestation of gouty panniculitis, with typical joint injuries, gouty tophi in
      both lower and upper extremities, chronic gouty tophi in the nose, for which only
      3 cases have been reported in literature, and great hypertrophy of adipose tissue
      in the lower back. CONCLUSIONS: Tophi can be found in atypical locations, which
      increase morbidities and deformities caused by the disease. We report an
      interesting case of gouty panniculitis associated with great hypertrophy of the
      adipose tissue, a rare manifestation of gout, and unusual locations of tophi.
      These clinical manifestations in our patient have not been recorded before, which
      leads us to think that we are in the presence of a new dermatological
      manifestation of gout.

PMID- 26301135
TI  - A Comprehensive Strategy for Reconstruction of a Missing Midface.
AB  - The loss of midface structures always leads to significant functional and
      cosmetic deficits, and the reconstruction work remains a challenge for surgeons.
      We report a rare case with severe midfacial defects involving the maxilla, nasal
      bone, and zygoma. This patient was treated with a comprehensive approach that
      included distraction osteogenesis, computer-aided surgery, a fibula bone graft,
      dental implantation, orthognathic surgery, and rhinoplasty. The treatment
      procedures required 4 years to complete, and a dramatically improved facial
      contour and stable occlusion were achieved. The results demonstrated the
      importance of a multidisciplinary approach and computer-aided design when
      treating severe maxillofacial deformities. Other important elements of the
      treatment process were the meticulous physical examination, the selection of an
      optimal treatment sequence, the skill of the surgeons, and more importantly, the
      patient-oriented mindset. 

PMID- 26301136
TI  - Subtotal Nasal Reconstruction: Military-civilian Collaboration in Care of an
      Afghan-American Woman's Plight.
AB  - Military plastic surgeons perform reconstructive surgeries for various
      congenital, oncologic, and traumatic craniofacial injuries or deformities.
      Recently, our Walter Reed National Military Medical Center Plastic Surgery team
      was tasked to care for a woman who bravely sought a new and better life in the
      United States after she suffered amputation of her nose and bilateral ears while
      in her home country of Afghanistan. A military-civilian team collaborated
      throughout her reconstructive planning, treatment, and postoperative course to
      create both an aesthetically acceptable and functional subtotal nasal
      reconstruction. This case report details the patient's unique journey, her
      reconstructive course, and highlights her reintegration into a new life and
      society. 

PMID- 26301137
TI  - Eyelid and Sternum Fibroblasts Differ in Their Contraction Potential and
      Responses to Inflammatory Cytokines.
AB  - BACKGROUND: Adverse skin scarring varies by anatomical site with, for example,
      presternal skin showing a greater hypertrophic response when compared with
      eyelid; such differences have traditionally been attributed to regional
      variations in skin tension, thickness, and Langer's lines. Fibroblasts are the
      main cell implicated in fibrosis, and they too are known to show anatomical
      variation in their expression, differentiation, and intercellular interactions.
      We, therefore, investigated whether intrinsic differences in skin fibroblasts
      derived from separate locations might contribute to the observed discrepancies in
      clinical scarring. METHODS: Primary in vitro cultures were established using
      matched eyelid and presternal skin from 3 healthy donors undergoing
      blepharoplasty surgery. We used an in vitro collagen gel model of fibroblast
      mediated tissue contraction to compare the properties of the dermal fibroblasts
      from each site. Cell contractile force and matrix stiffness were assessed in 3
      dimensional tissue constructs using an automated high-throughput device. RESULTS:
      Dermal fibroblasts isolated from eyelid and sternum differ both in their ability
      to contract a gel matrix and in their response to cytokine stimulation; despite
      having lower intrinsic contractile force (P < 0.01) and resting stiffness (P <
      0.02), the presternal cells were more contractile (P < 0.001) following
      stimulation with serum, or inflammatory cytokines transforming growth factor-beta
      (P < 0.01) and interleukin-1beta (P < 0.05). CONCLUSIONS: The propensity to
      cutaneous scarring may, at least in part, result from intrinsic differences in
      the local fibroblasts' ability to contract and their sensitivity to inflammatory
      cytokines. Improved understanding of the underlying molecular pathways should
      prove useful in identifying new therapeutic targets for altering surgical and
      other scarring.

PMID- 26301138
TI  - Microsurgical Lower Extremity Reconstruction in the Subacute Period: A Safe
      Alternative.
AB  - BACKGROUND: Microsurgical reconstruction of the lower extremity is an integral
      part of the limb salvage algorithm. Success is defined by a pain-free functional
      extremity, with a healed fracture and sufficient durable soft tissue coverage.
      Although early flap coverage of lower extremity fractures is an important goal,
      it is not always feasible because of multiple factors. Between the years 2000 and
      2010, approximately 50% of patients at Los Angeles County and University of
      Southern California Medical Center requiring microsurgical reconstruction did not
      receive soft tissue coverage until more than 15 days postinjury secondary to
      primary trauma, physiologic instability, patient comorbidities, or orthopedic and
      plastic surgery operative backlog. The objective of our study was to evaluate
      outcomes in patients who underwent microsurgical reconstruction of the lower
      extremity, in relation to the timing of reconstruction. METHODS: A retrospective
      chart review was performed for patients requiring immediate lower extremity
      reconstruction from January 2000 to December 2009 at LAC + USC. RESULTS: Fifty
      one patients were identified in this study. The most common mechanisms of injury
      were motorcycle, motor vehicle, and fall accidents. Eighty-six percent of
      injuries were open and 74% were comminuted. The distal 1/3 of the tibia,
      including the tibial pilon, was the most common location of injury. When
      comparing patients reconstructed in less than 15 days versus greater than or
      equal to 15 days, there was no significant difference in rates of flap failure,
      osteomyelitis, bony union, or ambulation. CONCLUSION: Microsurgical
      reconstruction of the lower extremity in the subacute period is a safe
      alternative.

PMID- 26301140
TI  - Three-Dimensional Changes of Maxilla after Secondary Alveolar Cleft Repair:
      Differences Between rhBMP-2 and Autologous Iliac Crest Bone Grafting.
AB  - BACKGROUND: Recombinant human bone morphogenetic protein (rhBMP)-2 has been used
      as an alternative to autologous bone transferring, a standard method of
      treatment. However, its potential adverse effect on anterior maxillary arch is
      unknown. Thus, the purpose of this study was to quantify sagittal and transversal
      changes of anterior maxilla after secondary alveolar cleft repair using
      traditional iliac crest bone grafting versus rhBMP-2. METHODS: Twelve unilateral
      complete cleft lip and palate patients were randomly divided into 2 groups. In
      group 1, patients underwent traditional iliac crest bone grafting transferring (n
      = 4), and in group 2, patients underwent alveolar cleft reconstruction using
      collagen matrix with lyophilized rhBMP-2 (n = 8). Computed tomography (CT)
      imaging was performed preoperatively and at 1 year postoperatively, using a
      previously standardized protocol. A three-dimensional (3D) CT cephalometric
      analysis of the linear and angular measurements of the sagittal and transverse
      maxilla planes was performed to assess intra- and intergroup maxillary changes.
      RESULTS: Intra- and intergroup comparisons of the pre- and postoperative 3D CT
      cephalometric linear and angular measurements of the sagittal and transverse
      maxilla planes showed no significant (all P > 0.05) differences among all studied
      variables. CONCLUSIONS: There were no significant anterior maxilla changes after
      maxillary cleft repair either using iliac crest bone grafting or rhBMP-2.

PMID- 26301139
TI  - Mastectomy Weight and Tissue Expander Volume Predict Necrosis and Increased Costs
      Associated with Breast Reconstruction.
AB  - INTRODUCTION: Impaired vascular perfusion in tissue expander (TE) breast
      reconstruction leads to mastectomy skin necrosis. We investigated factors and
      costs associated with skin necrosis in postmastectomy breast reconstruction.
      METHODS: Retrospective review of 169 women with immediate TE placement following
      mastectomy between May 1, 2009 and May 31, 2013 was performed. Patient
      demographics, comorbidities, intraoperative, and postoperative outcomes were
      collected. Logistic regression analysis on individual variables was performed to
      determine the effects of tissue expander fill volume and mastectomy specimen
      weight on skin necrosis. Billing data was obtained to determine the financial
      burden associated with necrosis. RESULTS: This study included 253 breast
      reconstructions with immediate TE placement from 169 women. Skin necrosis
      occurred in 20 flaps for 15 patients (8.9%). Patients with hypertension had 8
      times higher odds of skin necrosis [odd ratio (OR), 8.10, P < 0.001]. Patients
      with TE intraoperative fill volumes >300 cm(3) had 10 times higher odds of skin
      necrosis (OR, 10.66, P =0.010). Volumes >400 cm(3) had 15 times higher odds of
      skin necrosis (OR, 15.56, P = 0.002). Mastectomy specimen weight was correlated
      with skin necrosis. Specimens >500 g had 10 times higher odds of necrosis and
      specimens >1000 g had 18 times higher odds of necrosis (OR, 10.03 and OR, 18.43;
      P =0.003 and P <0.001, respectively). Mastectomy skin necrosis was associated
      with a 50% increased inpatient charge. CONCLUSION: Mastectomy flap necrosis is
      associated with HTN, larger TE volumes and mastectomy specimen weights, resulting
      in increased inpatient charges. Conservative TE volumes should be considered for
      patients with hypertension and larger mastectomy specimens.

PMID- 26301141
TI  - Interpositional Nerve Grafting of the Prostatic Plexus after Radical
      Prostatectomy.
AB  - BACKGROUND: Injury to the prostatic plexus may occur during radical prostatectomy
      even with the use of minimally invasive techniques. Reconstruction of these
      nerves by interpositional nerve grafting can be performed to reduce morbidity.
      Although the feasibility of nerve reconstruction has been shown, long-term
      functional outcomes are mixed, and the role of nerve grafting in these patients
      remains unclear. METHODS: A retrospective study was performed on 38 consecutive
      patients who underwent immediate unilateral or bilateral nerve reconstruction
      after open prostatectomy. Additionally, 53 control patients who underwent
      unilateral, bilateral, or non-nerve-sparing open prostatectomy without nerve
      grafting were reviewed. Outcomes included rates of urinary continence, erections
      sufficient for sexual intercourse, and ability to have spontaneous erections.
      Analysis was performed by stratifying patients by D'Amico score and laterality of
      nerve involvement. RESULTS: Unilateral nerve grafting conferred no significant
      benefit compared with unilateral nerve-sparing prostatectomy. Bilateral nerve
      sparing patients demonstrated superior functional outcomes compared with
      bilateral non-nerve-sparing patients, whereas bilateral nerve-grafting patients
      displayed a trend toward functional improvement. With increasing D'Amico score,
      there was a trend toward worsening urinary continence and erectile function
      regardless of nerve-grafting status. CONCLUSIONS: In the era of robotic
      prostatectomy, interpositional nerve reconstruction is not a routine practice.
      However, the substantial morbidity experienced in patients with bilateral nerve
      resections remains unacceptable, and therefore, nerve grafting may still improve
      functional outcomes in these patients. Further investigation is needed to improve
      the potential of bilateral nerve grafting after non-nerve-sparing prostatectomy.

PMID- 26301142
TI  - Reconstruction of Areolar Projection Using a Purse-String Suture Technique.
AB  - BACKGROUND: Nipple-areolar complex creation is the last step in the breast
      reconstruction process and plays a significant role in patients' overall
      satisfaction. Although numerous surgical techniques have been described to create
      the nipple, very few procedures address the natural contour of the areola.
      METHODS: We describe a surgical technique using a purse-string suture for
      improved areolar projection. After creation of nipple-areolar complex using a CV
      flap, evenly spaced stab incisions are made in a circular pattern, approximately
      5 mm outside of the boundary of the proposed areola. Using these incisions, a
      nonabsorbable purse-string suture is placed in the deep dermis. The diameter is
      cinched down to the desired measurement, providing areolar projection. RESULTS:
      Our experience using this technique has provided a satisfactory and stable
      projection of the areola in 10 patients with at least 1 year follow-up for each
      patient. There was no spitting of purse-string sutures in any of these patients,
      and there was no late areolar widening after at least 1 year follow-up. This
      provides a means for symmetry with an unreconstructed contralateral side.
      CONCLUSIONS: Improving aesthetic outcomes for areola reconstruction may further
      refine our goals of an ideal breast reconstruction.

PMID- 26301143
TI  - A Simple, Easy, and Reliable Technique of Phalangeal Corrective Osteotomy for
      Overlapping Fingers.
AB  - BACKGROUND: The theory that malrotation is best assessed by making a fist and
      looking for digital overlap was the basis for devising a simple, easy, and
      reliable technique for phalangeal corrective osteotomy. METHODS: This study
      assessed the phalangeal corrective osteotomy technique in 7 digits, involving 7
      cases in 6 patients; 1 patient required treatment bilaterally. This technique
      required the use of a small hologram 2-row plate and screws to maintain stable
      fixation during aggressive postoperative therapy. Evaluation of the clinical
      results was based on the total range of active motion (%TAM), the grading of
      results according to Buchler, and the severity of pain reported by patients using
      the visual analog scale. The disability of the arm, shoulder, and hand
      questionnaire was completed preoperatively and at final follow-up by patients.
      RESULTS: Corrective osteotomy corrected the overlapping of digits in all of the
      patients. There were no perioperative complications. Bone union was obtained in
      all cases, on average 13.4 weeks after surgery. Two osteotomies required
      secondary tenocapsulolysis concomitant with implant removal surgery. In light of
      total range of active motion and Buchler's grade, all the patients had excellent
      to good results for both criteria at final follow-up. No patient complained about
      pain. Mean disability of the arm, shoulder, and hand scores significantly
      decreased from 16.9 (range, 11.3-26.5) preoperatively to 3.9 (range, 0-7.6)
      postoperatively. CONCLUSIONS: Phalangeal corrective osteotomy was performed using
      a simple, easy, and reliable technique.

PMID- 26301145
TI  - Oral Mucosal Z-Plasty in Combination with Intravelar Veloplasty.
AB  - Our aim was to establish a reliable, functional surgical technique for soft
      palate closure. A step-by-step description of the operative procedure is
      presented. A cross-over procedure has been developed by combining the principles
      of a mucosal Z-plasty only on the oral side of the cleft palate, the intravelar
      veloplasty following Sommerlad's principles and a straight line closure on the
      nasal side. In the last 2 years, 25 patients have undergone the operation at the
      Cleft Centre of the 1st Paediatric Department of the Semmelweis University
      Budapest, Hungary. In all cases the operative technique could be adapted,
      operations were uneventful and straightforward. This technique was appropriate to
      close all the soft palate clefts, even the wide ones. This procedure combines the
      advantages of both procedures and has shown very good early postoperative
      results. 

PMID- 26301144
TI  - Deep Inferior Epigastric Artery Perforator Flap Breast Reconstruction without
      Microsurgery Fellowship Training.
AB  - BACKGROUND: Deep inferior epigastric artery perforator (DIEP) flap breast
      reconstruction requires complex microsurgical skills. Herein, we examine whether
      DIEP flap breast reconstruction can be performed safely without microsurgical
      fellowship training. METHODS: A total of 28 patients and 34 DIEP flaps were
      included in the study. We reviewed the medical records of patients for donor site
      and flap-related complications and analyzed the correlation between the
      complications and preoperative risk factors. We also performed a literature
      review to compare complication rates in our series with the literature. RESULTS:
      We observed total flap necrosis in 1 patient (2.9%), partial flap necrosis in 5
      patients (14.7%), infection in 1 patient (2.9%), hematoma/seroma in 3 patients
      (8.8%), donor site complications in 5 patients (18.5%), venous occlusion in 4
      patients (11.7%), and arterial occlusion in 1 patient (2.9%). We did not observe
      any correlation between complications and preoperative risk factors. Literature
      review yielded 18 papers that met our inclusion criteria. Partial flap necrosis
      rate was significantly higher in our series compared with literature (14.7% vs
      1.6%, P = 0.003). Venous complication rate was marginally higher in our series
      compared with literature (11.7% vs 3.3%, P = 0.057). However, total flap loss
      rate in our series was comparable with the literature (2.9% vs 2.2%, P = 0.759).
      CONCLUSION: With proper training during plastic surgery residency, DIEP flap can
      be performed with acceptable morbidity.

PMID- 26301146
TI  - Nodular Foot Myxedema Masquerading as Lymphedema.
AB  - Lymphedema results from abnormal development or injury to the lymphatic system.
      One-fourth of patients with lower extremity enlargement are erroneously labeled
      with "lymphedema." We describe a patient with hypothyroidism who developed soft
      tissue overgrowth of her foot. She was referred to our Lymphedema Program for
      management of "lymphedema" and overgrown toes. The patient's lymphoscintigram
      showed normal lymphatic function in her extremities, and she was diagnosed with
      myxedema by histopathology. Nodular localized myxedema should be included in the
      differential diagnosis of lymphedema. 

PMID- 26301147
TI  - Acute Hemorrhagic Flexor Tenosynovitis due to Vincula Injury.
AB  - A 20-year-old previously well woman presented to the emergency department with
      classical signs of acute flexor tenosynovitis, 4 hours after a minor puncture
      wound over the volar aspect of her right middle finger distal interphalangeal
      joint. Exploration of the flexor sheath in theatre revealed frank blood within
      the sheath and extension of the puncture wound through the profundus tendon into
      the short vincula beneath. The blood was irrigated from the sheath, and the
      patient made a complete recovery by 2 weeks postoperatively. Although rare,
      irritation and distension of the flexor sheath caused by vincular hemorrhage can
      be an alternative mechanism for the development of acute flexor tenosynovitis,
      and as with pyogenic flexor tenosynovitis, prompt surgical treatment can minimize
      the risk of long-term functional impairment. 

PMID- 26301148
TI  - Radiofrequency-Assisted Liposuction Compared with Aggressive Superficial,
      Subdermal Liposuction of the Arms: A Bilateral Quantitative Comparison.
AB  - BACKGROUND: Liposuction of the arms alone may be inadequate for aesthetic
      improvement because of skin laxity. Radiofrequency-assisted liposuction (RFAL)
      and aggressive superficial liposuction (SupL) have been described to stimulate
      soft tissue retraction to improve results. We compare the techniques and describe
      a classification scheme that factors skin laxity, skin quality, and Fitzpatrick
      type to provide treatment recommendations. METHODS: Ten consecutive female
      patients underwent RFAL of 1 arm and SupL on the contralateral arm. All patients
      had Fitzpatrick skin types of III, IV, or V with an average body mass index of
      26.0. Using fluorescent tattooing, key points on the arm skin were measured
      preoperatively and postoperatively to indicate changes in surface area. RESULTS:
      There were no complications in the group, and all patients reported satisfaction
      with the aesthetic results. All patients showed reduction of measured skin
      surface areas and skin distances postoperatively. At 1 year, the measured surface
      area reductions on the anterior arms averaged 15.0% for RFAL and 10.9% for SupL
      on the anterior arm skin. Posteriorly, RFAL showed 13.1% reduction and SupL 8.1%
      reduction in the surface areas at 1 year. Linear reduction for RFAL averaged
      22.6% and 17.8% for SupL 1 year postoperatively anteriorly. CONCLUSION: Both RFAL
      and SupL of the arms showed quantifiable and sustained reductions in skin
      surface. Good contour and soft tissue contraction were achieved with both
      techniques but RFAL with its safety features presents an alternative to SupL,
      which has a higher complication rate, risk for contour deformities, and steeper
      learning curve.

PMID- 26301149
TI  - Invasive Squamous Cell Carcinoma in Full-thickness Burn Wounds After Treatment
      with Cultured Epithelial Autografts.

PMID- 26301150
TI  - Does Liposuction Improve Body Image and Symptoms of Eating Disorders?
AB  - BACKGROUND: Unpleasant attention to unfavorable fat may have harmful
      psychological effects in terms of body dissatisfaction. As a consequence, this
      may cause abnormal eating regulation. It has been noted that women interested in
      liposuction self-report more eating problems. As far as we know, there are no
      prospective studies with standardized instruments providing sufficient data
      regarding the effects of aesthetic liposuction on various aspects of quality of
      life. Nevertheless, publications on the effects of eating habits are lacking.
      METHODS: Sixty-one consecutive women underwent aesthetic liposuction. Three
      outcome measures were applied at baseline and at follow-up: the eating disorder
      inventory, Raitasalo's modification of the Beck depression inventory, and the 15
      dimensional general quality of life questionnaire. RESULTS: The mean age at
      baseline was 44 years, and the mean body mass index was 26.0. Thirty-six (59%)
      women completed all outcome measures with a mean follow-up time of 7 months. A
      significant improvement from baseline to follow-up was noted in women's body
      satisfaction, and their overall risk for developing an eating disorder decreased
      significantly. CONCLUSION: Aesthetic liposuction results in a significantly
      reduced overall risk for an eating disorder in combination with improved body
      satisfaction.

PMID- 26301151
TI  - A Perforator Model as an Aid to Elevate Deep Inferior Epigastric Perforator Flap.

PMID- 26301152
TI  - Use of Intraoperative Computed Tomography for Revisional Procedures in Patients
      with Complex Maxillofacial Trauma.
AB  - BACKGROUND: In patients with panfacial fractures and distorted anatomic landmarks
      of zygomatic and orbital complex, there is a risk of zygomaticomaxillary complex
      (ZMC) malpositioning even with the best efforts for surgical repair. This results
      in increased number of additional procedures to achieve accurate positioning.
      METHODS: We describe the usage of intraoperative C-arm cone-beam computed
      tomographic (CT) scan for ZMC malpositioning in a representative patient with
      panfacial fractures. RESULTS: We have successfully used intraoperative CT scan
      for ZMC malpositioning in 3 patients. The representative patient had ZMC
      malposition after the initial attempt of surgical repair without any
      intraoperative imaging. On using intraoperative CT scan during the next attempt,
      we were able to reposition the ZMC accurately. CONCLUSIONS: Intraoperative CT
      scan might improve the accuracy of ZMC positioning and decrease the chances of
      potential additional surgeries. In patients with distorted anatomical landmarks
      and panfacial fractures, it can be especially helpful toward correcting ZMC
      malposition.

PMID- 26301153
TI  - The Shear Wave Velocity on Elastography Correlates with the Clinical Symptoms and
      Histopathological Features of Keloids.
AB  - BACKGROUND: Keloids present as red, painful lesions causing serious functional
      and cosmetic problems; however, there is no consensus regarding tools for
      objectively evaluating keloids. To demonstrate the utility of shear wave
      elastography in keloids, we investigated the correlations between clinical
      symptoms, ultrasound shear wave velocity, and histopathological findings.
      METHODS: Three patients with keloids containing both red hypertrophic and mature
      areas were evaluated using the shear wave velocity and histopathological
      findings. RESULTS: The results indicate that the shear wave velocity is high in
      active hypertrophic areas and low in mature areas. The areas with high
      elastography values exhibited numerous fibrillar collagenous matrices forming a
      whorled pattern with hyalinized tissue on hematoxylin-eosin staining
      corresponding with metachromasia on toluidine blue staining. In the mature area,
      the collagen fibers were oriented parallel to each other without metachromasia.
      CONCLUSIONS: Shear wave elastography provides quantitative estimates of tissue
      stiffness that correlate with the clinical symptoms and histopathological
      findings of the keloid lesions and can be used to assess the activity of keloids.

PMID- 26301154
TI  - Microsurgical Technique Modifications: Practical Tips for Improving Precision.
AB  - Supplemental Digital Content is available in the text. 

PMID- 26301155
TI  - Treatment of HIV-Infected Subjects with Buttock Lipoatrophy Using Stabilized
      Hyaluronic Acid Gel.
AB  - This prospective study explored effectiveness and safety of Macrolane VRF30 for
      treatment of buttock lipoatrophy in HIV-infected subjects. Ten subjects who were
      unable to sit for more than 30 minutes because of pain were injected with a mean
      of 276 mL and followed for 18 months. The pain score was reduced, and the time
      that subjects could sit was increased at least up to 9 months post treatment.
      There was no local displacement of gel. Five mild adverse events occurred; all
      related to the injection procedure. This pilot study indicates that Macrolane
      treatment of buttock lipoatrophy is a promising, well-tolerated method that
      reduces pain at sitting and improves buttock appearance. 

PMID- 26301156
TI  - Rotational Distraction for the Treatment of Severe Mandibular Retrognathia.
AB  - BACKGROUNDS: The main problem with intraoral distraction of the mandible is the
      inability to achieve the three-dimensional mandibular correction as planned
      preoperatively. We developed a technique that allows spontaneous changes in the
      direction of mandibular elongation using an intraoral distractor. METHODS: After
      mandibular osteotomy, the distractor is fixed to the distal segment of the
      mandible using a single bicortical screw, allowing anterior-posterior, vertical
      and limited lateromedial changes in the vector of distraction. Mandibular
      lengthening is performed while keeping the maxilla and mandible in class I
      occlusion with intermaxillary fixation. RESULTS: As the distraction device is
      activated allowing mandibular elongation, the proximal segment, guided by the
      surrounding soft tissues, moves and rotates posterosuperiorly. Mandibular
      lengthening is continued until the condylar head reaches an adequate position in
      the mandibular fossa as confirmed clinically and radiographically. CONCLUSION:
      Thirty-three patients with mandibular retrognathia received this treatment and
      good results were obtained.

PMID- 26301157
TI  - Autologous Graft Thickness Affects Scar Contraction and Quality in a Porcine
      Excisional Wound Model.
AB  - BACKGROUND: Texture, color, and durability are important characteristics to
      consider for skin replacement in conspicuous and/or mobile regions of the body
      such as the face, neck, and hands. Although autograft thickness is a known
      determinant of skin quality, few studies have correlated the subjective and
      objective characters of skin graft healing with their associated morphologic and
      cellular profiles. Defining these relationships may help guide development and
      evaluation of future skin replacement strategies. METHODS: Six-centimeter
      diameter full-thickness wounds were created on the back of female Yorkshire pigs
      and covered by autografts of variable thicknesses. Skin quality was assessed on
      day 120 using an observer scar assessment score and objective determinations for
      scar contraction, erythema, pigmentation, and surface irregularities.
      Histological, histochemical, and immunohistochemical assessments were performed.
      RESULTS: Thick grafts demonstrated lower observer scar assessment score (better
      quality) and decreased erythema, pigmentation, and surface irregularities.
      Histologically, thin grafts resulted in scar-like collagen proliferation while
      thick grafts preserves the dermal architecture. Increased vascularity and
      prolonged and increased cellular infiltration were observed among thin grafts. In
      addition, thin grafts contained predominately dense collagen fibers, whereas
      thick grafts had loosely arranged collagen. alpha-Smooth muscle actin staining
      for myofibroblasts was observed earlier and persisted longer among thinner
      grafts. CONCLUSIONS: Graft thickness is an important determinant of skin quality.
      High-quality skin replacements are associated with preserved collagen
      architecture, decreased neovascularization, and decreased inflammatory cellular
      infiltration. This model, using autologous skin as a metric of quality, may give
      a more informative analysis of emerging skin replacement strategies.

PMID- 26301158
TI  - Extraordinary Large Giant Congenital Melanocytic Nevus Treated with Integra
      Dermal Regeneration Template.
AB  - Garment-like giant congenital melanocytic nevi are very rare, and those being
      treated are most often offered excision and split-thickness skin transplantation.
      Due to the risk of restricted mobility secondary to shrinkage and hypertrophic
      scarring of the transplant, we treated to date the largest reported giant
      congenital melanocytic nevus (16% total body surface area) with Integra dermal
      regeneration template (Integra Life Sciences, Plainsboro, N.J.), giving a more
      functional skin reconstruction. In addition, the dermal regeneration template had
      to be covered with split-thickness skin transplant including multiple smaller
      nevi due to lack of larger area with normal skin. 

PMID- 26301159
TI  - Ossifying Fibroma of the Mandible: A Case Report Using Vascularized Free Fibula
      Flap Reconstruction.
AB  - We report a case of ossifying fibroma of the mandible in a 38-year-old woman. The
      mandibular resection involved the disarticulation of the condyle while preserving
      the articular disc. The segmental bony defect was then reconstructed with free
      fibula flap; the additional contouring of the distal fibular flap was performed
      during surgery to restore the patient's condylar function. A 2-year follow-up
      revealed the maintenance of excellent functional and aesthetic outcomes. 

PMID- 26301160
TI  - Hyperglycemia Interacts with Ischemia in a Synergistic Way on Wound Repair and
      Myofibroblast Differentiation.
AB  - BACKGROUND: Hyperglycemia is known to adversely affect the outcome of ischemic
      insults, but its interaction with ischemia has not been investigated in wound
      repair yet. In this study, we develop a new animal model allowing to investigate
      the interaction between hyperglycemia and ischemia during the wound repair
      process. We focus on myofibroblast differentiation, a key element of wound
      repair. METHODS: Ischemia was inflicted in Wistar rats by resection of the
      femoral to popliteal arteries on the left side, whereas arteries were dissected
      without resection on the right side. Full-thickness skin wounds (1 cm(2)) were
      created on both feet. Hyperglycemia was induced by injection of streptozotocin.
      Normoglycemic animals served as control (n = 23/group). Blood flow, wound
      closure, and myofibroblast expression were measured. RESULTS: Wound closure was
      significantly delayed in ischemic compared with nonischemic wounds in all rats.
      This delay was almost 5-fold exacerbated in hyperglycemic rats compared with
      normoglycemic rats, while hyperglycemia alone showed only a slight effect on
      wound repair. Delayed wound repair was associated with impaired wound contraction
      and myofibroblast differentiation. CONCLUSIONS: Our model allows to specifically
      quantify the effect of hyperglycemia and ischemia alone or in combination on
      wound repair. We show that hyperglycemia amplifies the inhibitory effect of
      ischemia on wound repair and myofibroblast expression. Our data reveal for the
      first time the synergic aspect of this interaction and therefore stress the
      importance of a strict glycemic control in the management of ischemic wounds.

PMID- 26301161
TI  - A New Approach to Minimize Acellular Dermal Matrix Use in Prosthesis-based Breast
      Reconstruction.
AB  - BACKGROUND: Acellular dermal matrices (ADMs) are often used to improve lower-pole
      contour, as well as allow for single-stage reconstruction, but numerous studies
      have shown an increased complication rate using ADM. As such, our group has
      developed a minimal-ADM-use technique to lower complications while effectively
      recreating lower-pole contour. METHODS: A total of 380 postmastectomy prosthesis
      based breast reconstructions were performed in 265 patients by a single surgeon.
      One hundred eight reconstructions were performed using the traditional ADM
      technique, with a large piece of ADM along the entire inferior and lateral
      borders. Two hundred twenty-five reconstructions were performed with the minimal
      use technique, patching only the lateral area of the reconstruction. Thirty-five
      reconstructions were performed without the use of any ADM for high-risk
      reconstructions, most often in morbidly obese patients. RESULTS: Comparing the
      traditional technique with the minimal-use technique, the seroma rate dropped
      from 3% to 0%. The rate of infection and reconstruction loss fell from 9% to 1%.
      Upon greatly reducing or eliminating the use of ADM use in obese patients, the
      seroma rate decreased from 15.4% to 5.7%, and the reconstruction loss rate
      decreased from 38% to 9%. CONCLUSIONS: This article describes a new surgical
      approach to minimize the amount of ADM necessary to create an aesthetically
      pleasing breast reconstruction. We believe that this approach helps avoid the
      complications of seroma, infection, and loss of the reconstruction. In certain
      obese patients, total avoidance of ADM may be the better choice.

PMID- 26301162
TI  - Can an Immediate 2-stage Breast Reconstruction Be Performed After Previous
      Conservative Surgery and Radiotherapy?
AB  - BACKGROUND: Prosthetic breast reconstruction is generally considered
      contraindicated after previous breast irradiation. As a result, patients
      undergoing a salvage mastectomy for recurrent breast cancer or "risk-reducing"
      mastectomies after previous conservative surgery and radiotherapy (CS + RT) are
      usually offered autologous breast reconstruction. However, not all such patients
      are suitable candidates for a major flap reconstruction. The purpose of this
      study is to review our results of immediate 2-stage prosthetic breast
      reconstruction after CS + RT. METHODS: A retrospective review was undertaken for
      671 consecutive patients with prosthetic-only breast reconstruction performed by
      a single surgeon over a 12.5-year period. Twenty-two patients who qualified for
      the criteria were audited. Outcomes examined include complications, loss of
      tissue expander or implant, revisional surgery, and aesthetic result. RESULTS:
      Twenty-two patients underwent 33 mastectomies and immediate 2-stage breast
      reconstructions after previous CS + RT (15 for recurrent cancer and seven "risk
      reduction") and 11 contralateral risk-reducing mastectomies. One patient died due
      to extensive metastatic disease. There was no reconstruction failure. The average
      breast implant size was 491.7 g (range 220 -685g). Seroma was the most common
      complication and occurred in 3 of 22 patients (13.6%) after stage 1 and 3 of 21
      patients (14.3%) after stage 2 reconstruction. The revisional surgery rate was
      28.6%. Aesthetic result was rated as excellent in 9.5%, good in 76.2%, and fair
      in 14.3%. CONCLUSIONS: For selected patients, immediate 2-stage prosthetic breast
      reconstruction can be performed successfully after a salvage mastectomy
      subsequent to a recurrence after CS + RT.

PMID- 26301163
TI  - Distraction Osteogenesis Technique for the Treatment of Nonsyndromic Sagittal
      Synostosis.
AB  - BACKGROUND: Historically, surgical treatment of children with a delayed
      presentation of cranial synostosis required complex cranial vault reconstruction.
      Recently, less invasive options for surgical correction, such as internal
      distraction osteogenesis, have been explored. In this study, we describe the
      successful management of delayed presentation of sagittal synostosis using
      distraction osteogenesis. METHODS: A bicoronal incision was made and 2 large
      rectangular osteotomies were performed bilaterally, involving the frontal,
      parietal, temporal and occipital bones. A 2 cm strut of bone over the sagittal
      sinus was preserved, creating bilateral free-floating bone segments. Two pairs of
      distractors were placed transversely, along the midline strut of bone, providing
      lateral distraction of these segments. This placement allowed maximum
      displacement at the apex of the cranial vault. Distraction was performed
      differentially at 1 mm per day anteriorly and 2 mm per day posteriorly, for a
      total of 17 days, allowing for a greater degree of expansion of the posterior
      vault. The consolidation phase lasted for 10 weeks. The distractors were removed
      via the same bicoronal incision and cranioplasty was performed to smooth
      prominent ridging at the margins of the distracted segments. RESULTS: The child's
      cranial index improved from 0.67 preoperatively to 0.76 postoperatively. The
      overall vault contour was smooth with no bony defects. There was a significant
      cosmetic improvement of the child's head shape. No major complications requiring
      reoperation or rehospitalization were encountered. CONCLUSION: The use of
      distraction osteogenesis to laterally expand the cranial vault is a useful
      alternative in the treatment of delayed presentation, nonsyndromic, sagittal
      synostosis.

PMID- 26301165
TI  - A universal symmetry detection algorithm.
AB  - Research on symmetry detection focuses on identifying and detecting new types of
      symmetry. The paper presents an algorithm that is capable of detecting any type
      of permutation-based symmetry, including many types for which there are no
      existing algorithms. General symmetry detection is library-based, but symmetries
      that can be parameterized, (i.e. total, partial, rotational, and dihedral
      symmetry), can be detected without using libraries. In many cases it is faster
      than existing techniques. Furthermore, it is simpler than most existing
      techniques, and can easily be incorporated into existing software. The algorithm
      can also be used with virtually any type of matrix-based symmetry, including
      conjugate symmetry. 

PMID- 26301164
TI  - Assessment by Ames test and comet assay of toxicity potential of polymer used to
      develop field-capable rapid-detection device to analyze environmental samples.
AB  - There is need for devices that decrease detection time of food-borne pathogens
      from days to real-time. In this study, a rapid-detection device is being
      developed and assessed for potential cytotoxicity. The device is comprised of
      melt-spun polypropylene coupons coated via oxidative chemical vapor deposition
      (oCVD) with 3,4-Ethylenedioxythiophene (EDOT), for conductivity and 3
      Thiopheneethanol (3TE), allowing antibody attachment. The Ames test and comet
      assay have been used in this study to examine the toxicity potentials of EDOT,
      3TE, and polymerized EDOT-co-3TE. For this study, Salmonella typhimurium strain
      TA1535 was used to assess the mutagenic potential of EDOT, 3TE and the copolymer.
      The average mutagenic potential of EDOT, 3TE and copolymer was calculated to be
      0.86, 0.56, and 0.92, respectively. For mutagenic potential, on a scale from 0 to
      1, close to 1 indicates low potential for toxicity, whereas a value of 0
      indicates a high potential for toxicity. The comet assay is a single-cell gel
      electrophoresis technique that is widely used for this purpose. This assay
      measures toxicity based on the area or intensity of the comet-like shape that DNA
      fragments produce when DNA damage has occurred. Three cell lines were assessed;
      FRhK-4, BHK-21, and Vero cells. After averaging the results of all three strains,
      the tail intensity of the copolymer was 8.8 % and tail moment was 3.0, and is
      most similar to the untreated control, with average tail intensity of 5.7 % and
      tail moment of 1.7. The assays conducted in this study provide evidence that the
      copolymer is non-toxic to humans.

PMID- 26301166
TI  - Tequila vinasses acidogenesis in a UASB reactor with Clostridium predominance.
AB  - Tequila vinasses represent an acidic, highly concentrated pollutant effluent
      generated during the distillation step of Tequila production. Although
      acidogenesis of Tequila vinasses has been reported for some reactor
      configurations, a characterization of the bacteria present during this metabolic
      process is lacking in the literature. Hydraulic retention times (HRT) between 36
      and 6 h and organic loading rates (OLR) from 5 to 30 g COD L(-1) d(-1) were
      assessed in a UASB reactor fed with Tequila vinasses. Results showed that OLR
      excerted a stronger effect (p <= 0.0001) on parameters such as gas production
      rate, pH, and acidity than HRT. While it was clear that shorter HRT were related
      to higher volatile fatty acid production levels. Figures above 2 Lgas Lreactor (
      1) d(-1) (where "gas" could be a mixture of methane and hydrogen) were attained
      only with an OLR as high as 30 g COD L(-1) d(-1). Bacterial identification of a
      sludge sample at the end of the experiment revealed that acid-tolerant
      microorganisms that remained in the reactor were exclusively affiliated to the
      Clostridium genera, being the first report of organisms identification for
      Tequila vinasses acidogenesis. These findings are relevant to the field of
      biotechnology since acidogenesis of Tequila vinasses using identified and studied
      microorganism abilities (i.e. Clostridium strains) presents the opportunity of
      optimizing processes intended for different metabolites production (butanol,
      volatile fatty acids, hydrogen, solvents). 

PMID- 26301167
TI  - Trends in penile cancer: a comparative study between Australia, England and
      Wales, and the US.
AB  - PURPOSE: To investigate and compare the trends in incidence and mortality of
      penile cancer between Australia, England and Wales, and the US, and provide
      hypotheses for these trends. METHODS: Cancer registry data from 1982 to 2005
      inclusive were obtained from Australia, England and Wales, and the United States.
      From these data, age-specific, -standardised and mortality:incidence ratios were
      calculated, and compared. RESULTS: The overall incidence of penile cancer in
      England and Wales (1.44 per 100,000 man-years) was higher than in Australia (0.80
      per 100,000), and the US (0.66 per 100,000). Incidence of penile cancer in all
      three countries has remained relatively stable over time. Similarly, although the
      mortality rates were also higher in England and Wales (0.37 per 100,000 man
      years) compared to Australia (0.18 per 100,000) and the US (0.15 per 100,000),
      the mortality/incidence ratios were similar for all three countries. CONCLUSIONS:
      Penile cancer incidence is low, affecting mainly older men. Rates differ between
      the three countries, being twice as common in England and Wales as in the other
      studied regions. Circumcision rates have a potential influence on these rates but
      are not the sole explanation for the variation.

PMID- 26301168
TI  - Heparin-induced thrombocytopenia in a non-heparin-naive patient: a case report.
AB  - INTRODUCTION: Administration of low molecular weight heparin (LMWH) is
      recommended for prophylaxis of venous thromboembolism in patients undergoing hip
      surgery. In this context, heparin-induced thrombocytopenia (HIT) type II is a
      complication of rare incidence but sometimes fatal outcome. CASE DESCRIPTION: A
      52-year old obese patient undergoing antithrombotic therapy with Enoxaparin after
      hip surgery presented with a painful, swollen leg and thrombocytopenia on day
      eight after surgery. Medical history showed previous administration of Enoxaparin
      without complications 2 years ago. Further diagnostic investigation supplied
      evidence of multiple thromboembolic events and concomitant compartment syndrome.
      Administration of Enoxaparin was stopped immediately and treatment with
      Argatroban was initiated. Diagnosis of HIT was confirmed according to current
      guidelines. Despite interventional thrombectomy and fasciotomy, amputation of
      both lower limbs had to be performed due to ongoing necroses. After a 30-days
      stay at the intensive care unit because of sepsis, respiratory and renal failure,
      clinical condition improved and the patient could be transferred for
      rehabilitation. DISCUSSION AND EVALUATION: HIT II is known as complication of
      administration of LMWH in the perioperative setting. Diagnosis results from
      clinical findings and platelet count. Argatroban is recommended as an alternative
      therapeutic anticoagulant in HIT II. Inflammation and surgical trauma are
      discussed as priming factors to increase risk of HIT II. CONCLUSIONS:
      Administration of LMWH may result in HIT II despite prior uneventful drug
      exposure. Except for immediate diagnosis, only consequent anticoagulation can
      stop the course of disease. Hence, interdisciplinary awareness is inevitable for
      early diagnosis and accurate therapy to prevent from a catastrophic clinical
      course.

PMID- 26301169
TI  - Transcatheter embolization for hemoptysis associated with anomalous systemic
      artery in a patient with scimitar syndrome.
AB  - BACKGROUND: Scimitar syndrome can present with a wide clinical spectrum of
      symptoms either early in the neonatal period or later in life. CASE DESCRIPTION:
      We report a case of a 62-year-old woman with anomalous systemic arterial supply
      to the basal lung with scimitar syndrome presenting as recurrent hemoptysis.
      Bronchoscopy revealed normal major bronchial branches without bronchial atresia,
      indicating that sequestration of the lung was not confirmed. The anomalous
      drainage of the scimitar vein was to the inferior vena cava, and an anomalous
      artery from the aorta supplied the right basal lung. There were no findings of
      pulmonary hypertension and arteriovenous malformation such as an anomalous artery
      to the scimitar vein. The distal portions of anomalous arteries were embolized
      using gelatin sponge particles and the proximal portion was embolized using
      fibered detachable coils. Although a small pulmonary infarction was observed as a
      complication, the patie nt has not experienced any subsequence recurrence of the
      hemoptysis during a follow-up period of 6 months. DISCUSSION AND EVALUATION:
      Deformities of the blood vessels and the lungs are frequently complex in scimitar
      syndrome. Although patients treated with surgical repair of this disorder may be
      at higher risk than those treated less invasively, we believe that transcatheter
      embolization was a useful strategy for the treatment of the anomalous systemic
      arterial supply to the basal lung, particularly in this patient with scimitar
      syndrome. CONCLUSION: Hemoptysis in a patient with scimitar syndrome associated
      with anomalous systemic arterial supply to the basal lung was successfully
      treated with transcatheter arterial embolization. However, it might be better to
      avoid the use of gelatin sponge particles in patients with a similar anomaly
      without pulmonary artery distribution because of the possibility of causing
      severe pulmonary infarction.

PMID- 26301170
TI  - Study protocol: mobile improvement of self-management ability through rural
      technology (mI SMART).
AB  - BACKGROUND: There are 62 million Americans currently residing in rural areas who
      are more likely to have multiple chronic conditions and be economically
      disadvantaged, and in poor health, receive less recommended preventive services
      and attend fewer visits to health care providers. Recent advances in mobile
      healthcare (mHealth) offer a promising new approach to solving health disparities
      and improving chronic illness care. It is now possible and affordable to transmit
      health information, including values from glucometers, automated blood pressure
      monitors, and scales, through Bluetooth-enabled devices. Additionally, audio and
      video communications technologies can allow healthcare providers to conduct many
      parts of a physical exam remotely from varied settings. These technologies could
      remove geographical distance as a barrier to care and diminish the access to care
      issues faced by patients who live rurally. However, currently there is lack of
      studies that provide evidence of feasibility, acceptability, and effectiveness of
      mHealth initiatives on improved outcomes of care, a needed step to make the
      translation to implementation studies in healthcare systems. The purpose of this
      paper is to present the protocol for the first study of mI SMART (mobile
      Improvement of Self-Management Ability through Rural Technology), a new
      integrated mHealth intervention. METHODS: Our objective is to provide evidence of
      feasibility and acceptability for the use of mI SMART in an underserved
      population and establish evidence for the refinement of mI SMART. The proposed
      study will take place at Milan Puskar Health Right, a free primary care clinic in
      the state of West Virginia. The clinic provides health care at no cost to
      uninsured, low income; adults aged 18-64 living in West Virginia. We will enroll
      30 participants into this feasibility study with plans of implementing a
      longitudinal randomized, comparative effectiveness design in the future. Data
      collection will include tracking of barriers and facilitators to using mI SMART
      on patient and provider feedback surveys, tracking of patient-provider
      communications, self-reports from patients on quality of life, adherence, and
      self-management ability, and capture of health record data on chronic illness
      measures. DISCUSSION: We expect that the mI SMART intervention, refined from
      participant and provider feedback, will be acceptable and feasible. We anticipate
      high patient-provider satisfaction, enhanced patient-provider communication, and
      improved health related quality of life, adherence to treatment, and self
      management ability. In addition, we hypothesize that patients who use mI SMART
      will demonstrate improved physical outcomes such as blood glucose, blood
      pressure, and weight.

PMID- 26301172
TI  - Psychological and Neurobiological Precursors of Alcohol Use Disorders in High
      Risk Youth.
AB  - It has long been known that Alcohol Use Disorders (AUDs) run in families with
      substantial heritability. Determining the specific genetic underpinnings of these
      disorders has been challenging because of the clinical heterogeneity and variable
      expression across the lifespan. The search for endophenotypic biological
      variation associated with the AUD and related substance use disorder (SUD)
      phenotypes is based on the belief that an endophenotype is more proximal to the
      causative gene. Identification of genes conferring increased susceptibility has
      important implications for treatment through the potential development of
      medications that target specific genetic pathways. High risk family designs that
      contrast offspring with and without a familial/genetic background have provided
      valuable insights into the psychological characteristics (executive control,
      affective regulation, decision making and social cognition) that differentiate
      such individuals. The current chapter will review these with a focus on brain
      morphology of specific regions, the coordinated activity of neural networks, and
      developmental trajectories of electrophysiological activity.

PMID- 26301171
TI  - Nicotinic receptor contributions to smoking: insights from human studies and
      animal models.
AB  - It is becoming increasingly evident that a variety of factors contribute to
      smoking behavior. Nicotine is a constituent of tobacco smoke that exerts its
      psychoactive effects via binding to nicotinic acetylcholine receptors (nAChRs) in
      brain. Human genetic studies have identified polymorphisms in nAChR genes, which
      predict vulnerability to risk for tobacco dependence. In vitro studies and animal
      models have identified the functional relevance of specific polymorphisms.
      Together with animal behavioral models, which parse behaviors believed to
      contribute to tobacco use in humans, these studies demonstrate that nicotine
      action at a diversity of nAChRs is important for expression of independent
      behavioral phenotypes, which support smoking behavior.

PMID- 26301173
TI  - Genetic and Environmental Interplay in Adolescent Substance Use Disorders.
AB  - Adolescent substance use is of considerable public health importance. This
      narrative review provides a brief background to genetically informative research
      methodologies and highlights key recent literature examining the interplay
      between genetic and environmental influences in the etiology of substance use.
      Twin studies have quantified the magnitude of genetic and environmental
      influences, and more recently co-relative and Children of Twin designs have shown
      environments can moderate heritability. Studies have identified a number of
      specific gene variants (e.g. OPRM1, DRD4, 5HTTLPR) that interact with parenting
      and peer influence, and the effectiveness of interventions may vary by genotype.
      However, little research has taken into account the stage-sequential nature of
      substance use. This may obscure important differences in the genetic and
      environmental influences, and their interplay, at the stages of escalation to
      problem use. Future research needs to build on existing methodologies to
      disentangle the complexities of progression in adolescent substance use.

PMID- 26301174
TI  - Monocyte-Derived Suppressor Cells in Transplantation.
AB  - Myeloid-derived suppressor cells (MDSC) are cells of myeloid origin with enhanced
      suppressive function. They are negative regulators of the immune responses and
      comprise a heterogeneous mixture of immunosuppressive cells of monocytic (M-MDSC)
      and granulocytic (G-MDSC) origin. A more recent nomenclature proposes the term
      "suppressive monocyte derived cells" (suppressive MCs) to define CSF1/CSF2
      dependent mouse suppressor cells that develop from common monocyte progenitors
      (cMoPs) after birth. Here, we review the literature about monocytic-derived cells
      with demonstrated suppressor function in vitro and in vivo within the context of
      solid organ transplantation.

PMID- 26301175
TI  - Current and emergent treatments for symptoms and neurocognitive impairment in
      schizophrenia.

PMID- 26301176
TI  - Glutamatergic agents for OCD and related disorders.
AB  - Pharmacotherapy remains inadequate for many patients with OCD; there is an urgent
      need for alternative pharmacological strategies. Convergent evidence suggests
      imbalance in glutamate, the brain's primary excitatory neurotransmitter, in some
      patients. This has motivated interest in glutamate modulators in patients who are
      unresponsive to standard pharmacotherapeutic approaches. While no glutamate
      modulator can be considered proven as an efficacious treatment of OCD, promising
      suggestions of benefit have been reported for memantine and riluzole. The
      evidence is thinner for N-acetylcysteine, but this agent's low cost and benign
      side effect profile make it a reasonable consideration in certain patients.
      Intriguing research on D-cycloserine and ketamine suggest potential benefit as
      well. It is notable that these agents all work by different, and in some cases
      opposite, mechanisms; this suggests that we have much to learn about the role of
      glutamate dysregulation in the etiology of OCD, and of glutamate modulators in
      its treatment.

PMID- 26301177
TI  - Effects of minimum legal drinking age on alcohol and marijuana use: evidence from
      toxicological testing data for fatally injured drivers aged 16 to 25 years.
AB  - BACKGROUND: Alcohol and marijuana are among the most commonly used drugs by
      adolescents and young adults. The question of whether these two drugs are
      substitutes or complements has important implications for public policy and
      prevention strategies, especially as laws regarding the use of marijuana are
      rapidly changing. METHODS: Data were drawn from fatally injured drivers aged 16
      to 25 who died within 1 h of the crash in nine states with high rates of
      toxicology testing based from 1999 to 2011 on the Fatality Analysis Reporting
      System (N = 7,191). Drug tests were performed using chromatography and
      radioimmunoassay techniques based on blood and/or urine specimens. Relative risk
      regression and Joinpoint permutation analysis were used. RESULTS: Overall, 50.5%
      of the drivers studied tested positive for alcohol or marijuana. Univariable
      relative risk modeling revealed that reaching the minimum legal drinking age was
      associated with a 14% increased risk of alcohol use (RR = 1.14, 95% CI: 1.02 to
      1.28), a 24% decreased risk of marijuana use (RR = 0.76, 95% CI: 0.53 to 1.10),
      and a 22% increased risk of alcohol plus marijuana use (RR=1.22, 95% CI: 0.90 to
      1.66). Joinpoint permutation analysis indicated that the prevalence of alcohol
      use by age is best described by two slopes, with a change at age 21. There was
      limited evidence for a change at age 21 for marijuana use. CONCLUSIONS: These
      results suggest that among adolescents and young adults, increases in alcohol
      availability after reaching the MLDA have marginal effect on marijuana use.

PMID- 26301178
TI  - Do Elite Athletes Live Longer? A Systematic Review of Mortality and Longevity in
      Elite Athletes.
AB  - BACKGROUND: Understanding of an athlete's lifespan is limited with a much more
      sophisticated knowledge of their competitive careers and little knowledge of post
      career outcomes. In this review, we consider the relationship between
      participation at elite levels of sport and mortality risk relative to other
      athletes and age- and sex-matched controls from the general population. Our
      objective was to identify, collate, and disseminate a comprehensive list of risk
      factors associated with longevity and trends and causes of mortality among elite
      athletes. METHODS: English language articles were searched using the Web of
      Science database. Keywords athletes, death, elite, "high performance" life
      expect*, longevity, mortality, players, professional, and sport were used to
      locate research articles. Seventeen additional articles were retrieved from
      reference lists found in these papers and a general web search. The inclusion
      criteria were the following: (1) publication year 1980 or later; (2) the study
      examined elite-level athletes; and (3) outcome data measured mortality/longevity
      trends and/or causes. RESULTS: Fifty-four peer-reviewed publications and three
      articles from online sources met the criteria for inclusion. Baseball, football,
      soccer, basketball, and cycling had the most reported data on elite athletes'
      lifespan longevities. A variety of mechanisms have attempted to explain mortality
      risk (e.g., handedness, playing position, achievement, etc.). Considerable
      support was found for superior longevity outcomes for elite athletes,
      particularly those in endurance and mixed sports. CONCLUSIONS: Future research
      into the mechanisms that may affect mortality risk is important for a better
      understanding of life expectancies in both eminent and non-eminent populations.
      Participation in elite sport is generally favorable to lifespan longevity. KEY
      POINTS: A majority of studies included in this review reported superior lifespan
      longevity outcomes for elite athletes compared to age- and sex-matched controls
      from the general population and other athletes.Several mechanisms within and
      between sports may have powerful effects on the overall lifespan longevities of
      players (e.g., type of sport, playing position, race, and energy system).Future
      research on mortality in elite athletes would benefit from more comprehensive
      statistical measures and reliable databases to determine potential mechanisms
      that may influence mortality trends and causes in both athlete and non-athlete
      samples.

PMID- 26301179
TI  - Arthroscopic approach to the posterior compartment of the knee using a posterior
      transseptal portal.
AB  - Arthroscopic surgery of the posterior compartment of the knee is difficult when
      only two anterior portals are used for access because of the inaccessibility of
      the back of the knee. Since its introduction, the posterior transseptal portal
      has been widely employed to access lesions in the posterior compartment. However,
      special care should be taken to avoid neurovascular injuries around the
      posteromedial, posterolateral, and transseptal portals. Most importantly,
      popliteal vessel injury should be avoided when creating and using the transseptal
      portal during surgery. Purpose of the present study is to describe how to avoid
      the neurovascular injuries during establishing the posterior three portals and to
      introduce our safer technique to create the transseptal portal. To date, we have
      performed arthroscopic surgeries via the transseptal portal in the posterior
      compartments of 161 knees and have not encountered nerve or vascular injury. In
      our procedure, the posterior septum is perforated with a 1.5-3.0-mm Kirschner
      wire that is protected by a sheath inserted from the posterolateral portal and
      monitored from the posteromedial portal to avoid popliteal vessel injury. 

PMID- 26301180
TI  - Cost analysis and outcomes of simple elbow dislocations.
AB  - AIM: To evaluate the management, clinical outcome and cost implications of three
      different treatment regimes for simple elbow dislocations. METHODS: Following
      institutional board approval, we performed a retrospective review of all
      consecutive patients treated for simple elbow dislocations in a Level I trauma
      centre between January 2008 and December 2010. Based on the length of elbow
      immobilisation (LOI), patients were divided in three groups (Group I, < 2 wk;
      Group II, 2-3 wk; and Group III, > 3 wk). Outcome was considered satisfactory
      when a patient could achieve a pain-free range of motion >= 100 degrees  (from 30
      degrees  to 130 degrees ). The associated direct medical costs for the treatment
      of each patient were then calculated and analysed. RESULTS: We identified 80
      patients who met the inclusion criteria. Due to loss to follow up, 13 patients
      were excluded from further analysis, leaving 67 patients for the final analysis.
      The mean LOI was 14 d (median 15 d; range 3-43 d) with a mean duration of
      hospital engagement of 67 d (median 57 d; range 10-351 d). Group III (prolonged
      immobilisation) had a statistically significant worse outcome in comparison to
      Group I and II (P = 0.04 and P = 0.01 respectively); however, there was no
      significant difference in the outcome between groups I and II (P = 0.30). No
      statistically significant difference in the direct medical costs between the
      groups was identified. CONCLUSION: The length of elbow immobilization doesn't
      influence the medical cost; however immobilisation longer than three weeks is
      associated with persistent stiffness and a less satisfactory clinical outcome.

PMID- 26301181
TI  - Can tranexamic acid change preoperative anemia management during total joint
      arthroplasty?
AB  - AIM: To investigate the postoperative transfusion and complication rates of
      anemic and nonanemic total joint arthroplasty patients given tranexamic acid
      (TXA). METHODS: A cross-sectional prospective study was conducted of primary hip
      and knee arthroplasty cases performed from 11/2012 to 6/2014. Exclusion criteria
      included revision arthroplasty, bilateral arthroplasty, acute arthroplasty after
      fracture, and contraindication to TXA. Patients were screened prior to surgery,
      with anemia was defined as hemoglobin of less than 12 g/dL for females and of
      less than 13 g/dL for males. Patients were divided into four different groups,
      based on the type of arthroplasty (total hip or total knee) and hemoglobin status
      (anemic or nonanemic). Intraoperatively, all patients received 2 g of intravenous
      TXA during surgery. Postoperatively, allogeneic blood transfusion (ABT) was
      directed by both clinical symptoms and relative hemoglobin change. Complications
      were recorded within the first two weeks after surgery and included
      thromboembolism, infection, and wound breakdown. The differences in transfusion
      and complication rates, as well as the relative hemoglobin change, were compared
      between anemic and nonanemic groups. RESULTS: A total of 232 patients undergoing
      primary joint arthroplasty were included in the study. For the total hip
      arthroplasty cohort, 21% (18/84) of patients presented with preoperative anemia.
      Two patients in the anemic group and two patients in the nonanemic group needed
      ABTs; this was not significantly different (P = 0.20). One patient in the anemic
      group presented with a deep venous thromboembolism while no patients in the
      nonanemic group had an acute complication; this was not significantly different
      (P = 0.21). For nonanemic patients, the average change in hemoglobin was 2.73 +/-
      1.17 g/dL. For anemic patients, the average change in hemoglobin was 2.28 +/-
      0.96 g/dL. Between the two groups, the hemoglobin difference of 0.45 g/dL was not
      significant (P = 0.13). For the total knee arthroplasty cohort, 18% (26/148) of
      patients presented with preoperative anemia. No patients in either group required
      a blood transfusion or had an acute postoperative complication. For nonanemic
      patients, the average change in hemoglobin was 1.85 +/- 0.79 g/dL. For anemic
      patients, the average change in hemoglobin was 1.09 +/- 0.58 g/dL. Between the
      two groups, the hemoglobin difference of 0.76 g/dL was significant (P < 0.001).
      CONCLUSION: TXA administration results in low transfusion and complication rates
      and may be a useful adjunct for TJA patients with preoperative anemia.

PMID- 26301182
TI  - Persistent post-surgical pain and neuropathic pain after total knee replacement.
AB  - AIM: To study the prevalence of persistent post-surgical pain (PPSP) and
      neuropathic pain (NP) after total knee replacement (TKR). METHODS: MEDLINE and
      Embase databases were searched for articles published until December 2014 in
      English language. Published articles were included if they referred to pain that
      lasts at least 3 mo after primary TKR for knee osteoarthritis, and measured pain
      with pain specific instruments. Studies that referred to pain caused by septic
      reasons and implant malalignment were excluded. Both prospective and
      retrospective studies were included and only 14 studies that match the inclusion
      criteria were selected for this review. RESULTS: The included studies were
      characterized by the heterogeneity on the scales used to measure pain and pre
      operative factors related to PPSP and NP. The reported prevalence of PPSP and NP
      seems to be relatively high, but it varies among different studies. There is also
      evidence that the prevalence of post-surgical pain is related to the scale used
      for pain measurement. The prevalence of PPSP is ranging at 6 mo from 16% to 39%
      and at 12 mo from 13.1% to 23% and even 38% of the patients. The prevalence of NP
      at 6 mo post-operatively is ranging from 5.2% to 13%. Pre-operative factors
      related to the development of PPSP also differ, including emotional functioning,
      such as depression and pain catastrophizing, number of comorbidities, pain
      problems elsewhere and operations in knees with early grade of osteoarthritis.
      CONCLUSION: No firm conclusions can be reached regarding the prevalence of PPSP
      and NP and the related factors due to the heterogeneity of the studies.

PMID- 26301184
TI  - Florid reactive periostitis ossificans of the humerus: Case report and
      differential diagnosis of periosteal lesions of long bones.
AB  - A case of florid reactive periostitis ossificans (RPO) arising in a long bone is
      presented. This is a rare bone proliferation with a pronounced periosteal
      reaction. Less than 100 cases have been described in the literature with far
      fewer outside the bones of the hand, feet, fingers, and toes. Although the
      etiology is unknown, a relationship to preceding trauma is suggested. The imaging
      and histologic features show an overlap with other bone lesions including bizarre
      parosteal osteochondromatous proliferation, subungual exostosis, and malignant
      surface tumors of bone and cartilage which include, periosteal and parosteal
      osteosarcoma. It is important to recognize the clinical presentation and
      diagnostic features of RPO as a benign entity so that it is not mistaken for a
      more aggressive neoplasm. We present a case of a right distal humeral lesion that
      on histopathological review revealed florid RPO. This diagnosis was not suspected
      on imaging studies, but was made on open biopsy of the mass. The patient remains
      disease free, years postoperatively. In addition to presenting this unique case
      report, we review the pertinent literature, and offer a differential diagnosis
      and treatment strategy for its management. 

PMID- 26301183
TI  - Predictors of spine deformity progression in adolescent idiopathic scoliosis: A
      systematic review with meta-analysis.
AB  - AIM: To evaluate published data on the predictors of progressive adolescent
      idiopathic scoliosis (AIS) in order to evaluate their efficacy and level of
      evidence. METHODS:  SELECTION CRITERIA: (1) study design: randomized controlled
      clinical trials, prospective cohort studies and case series, retrospective
      comparative and none comparative studies; (2) participants: adolescents with AIS
      aged from 10 to 20 years; and (3) treatment: observation, bracing, and other.
      SEARCH METHOD: Ovid MEDLINE, Embase, the Cochrane Library, PubMed and patent data
      bases. All years through August 2014 were included. Data were collected that
      showed an association between the studied characteristics and the progression of
      AIS or the severity of the spine deformity. Odds ratio (OR), sensitivity,
      specificity, positive and negative predictive values were also collected. A meta
      analysis was performed to evaluate the pooled OR and predictive values, if more
      than 1 study presented a result. The GRADE approach was applied to evaluate the
      level of evidence. RESULTS: The review included 25 studies. All studies showed
      statistically significant or borderline association between severity or
      progression of AIS with the following characteristics: (1) An increase of the
      Cobb angle or axial rotation during brace treatment; (2) decrease of the rib
      vertebral angle at the apical level of the convex side during brace treatment;
      (3) initial Cobb angle severity (> 25(o)); (4) osteopenia; (5) patient age < 13
      years at diagnosis; (6) premenarche status; (7) skeletal immaturity; (8) thoracic
      deformity; (9) brain stem vestibular dysfunction; and (10) multiple indices
      combining radiographic, demographic, and physiologic characteristics. Single
      nucleotide polymorphisms of the following genes: (1) calmodulin 1; (2) estrogen
      receptor 1; (3) tryptophan hydroxylase 1; (3) insulin-like growth factor 1; (5)
      neurotrophin 3; (6) interleukin-17 receptor C; (7) melatonin receptor 1B, and (8)
      ScoliScore test. Other predictors included: (1) impairment of melatonin signaling
      in osteoblasts and peripheral blood mononuclear cells (PBMC); (2) G-protein
      signaling dysfunction in PBMC; and (3) the level of platelet calmodulin. However,
      predictive values of all these findings were limited, and the levels of evidence
      were low. The pooled result of brace treatment outcomes demonstrated that around
      27% of patents with AIS experienced exacerbation of the spine deformity during or
      after brace treatment, and 15% required surgical correction. However, the level
      of evidence is also low due to the limitations of the included studies.
      CONCLUSION: This review did not reveal any methods for the prediction of
      progression in AIS that could be recommended for clinical use as diagnostic
      criteria.

PMID- 26301185
TI  - Political advocacy in pharmacy: challenges and opportunities.
AB  - Many pharmacists have expressed a desire to become more involved in patient care,
      in part by being compensated for patient counseling, as well as by providing
      services traditionally offered by physicians and nurse practitioners. Recent
      efforts to develop collaborative care models, as well as major restructurings of
      US health insurance coverage, provide a unique opportunity for pharmacists to
      become recognized as independent health care providers and be reimbursed as
      primary care providers. Achieving that goal would require addressing advocacy
      challenges familiar to other health care professionals who have achieved provider
      status under existing reimbursement rules. Historically, political advocacy has
      not been a major part of pharmacy practice, or even viewed as necessary. However,
      pharmacists would be more politically effective with a single organization to
      speak for them as a profession, and with further education in advocacy.

PMID- 26301188
TI  - Glycemic Variability: How Do We Measure It and Why Is It Important?
AB  - Chronic hyperglycemia is the primary risk factor for the development of
      complications in diabetes mellitus (DM); however, it is believed that frequent or
      large glucose fluctuations may independently contribute to diabetes-related
      complications. Postprandial spikes in blood glucose, as well as hypoglycemic
      events, are blamed for increased cardiovascular events in DM. Glycemic
      variability (GV) includes both of these events; hence, minimizing GV can prevent
      future cardiovascular events. Correcting GV emerges as a target to be pursued in
      clinical practice to safely reduce the mean blood glucose and to determine its
      direct effects on vascular complications in diabetes. Modern diabetes management
      modalities, including glucagon-related peptide-1-based therapy, newer insulins,
      modern insulin pumps and bariatric surgery, significantly reduce GV. However,
      defining GV remains a challenge primarily due to the difficulty of measuring it
      and the lack of consensus regarding the optimal approach for its management. The
      purpose of this manuscript was not only to review the most recent evidence on GV
      but also to help readers better understand the available measurement options and
      how the various definitions relate differently to the development of diabetic
      complications. 

PMID- 26301189
TI  - Peripheral Arterial Disease in Patients with Type 2 Diabetes Mellitus.
AB  - Peripheral arterial disease (PAD) in patients with type 2 diabetes mellitus
      (T2DM) exhibits broad clinical characteristics and various consequences and is
      known as one of the major macrovascular complications of T2DM. Atherosclerosis is
      recognized as the most direct and important cause of PAD, but acute or chronic
      limb ischemia may be the result of various risk factors. In light of the
      increasing number of patients who undergo peripheral vascular procedures, the
      number of subjects who are exposed to the risks for PAD and related complications
      is increasing. In this review, we will discuss the clinical and epidemiological
      characteristics of PAD, as well as the clinical significance of PAD in T2DM
      subjects. 

PMID- 26301191
TI  - Effects of Sitagliptin on Insulin and Glucagon Levels in Type 2 Diabetes
      Mellitus.

PMID- 26301190
TI  - Probiotics as Complementary Treatment for Metabolic Disorders.
AB  - Over the past decade, growing evidence has established the gut microbiota as one
      of the most important determinants of metabolic disorders such as obesity and
      type 2 diabetes. Indeed, obesogenic diet can drastically alter bacterial
      populations (i.e., dysbiosis) leading to activation of pro-inflammatory
      mechanisms and metabolic endotoxemia, therefore promoting insulin resistance and
      cardiometabolic disorders. To counteract these deleterious effects, probiotic
      strains have been developed with the aim of reshaping the microbiome to improve
      gut health. In this review, we focus on benefits of widely used probiotics
      describing their potential mechanisms of action, especially their ability to
      decrease metabolic endotoxemia by restoring the disrupted intestinal mucosal
      barrier. We also discuss the perspective of using new bacterial strains such as
      butyrate-producing bacteria and the mucolytic Akkermansia muciniphila, as well as
      the use of prebiotics to enhance the functionality of probiotics. Finally, this
      review introduces the notion of genetically engineered bacterial strains
      specifically developed to deliver anti-inflammatory molecules to the gut. 

PMID- 26301192
TI  - Current Status of Management in Type 2 Diabetes Mellitus at General Hospitals in
      South Korea.
AB  - BACKGROUND: In Korea, the prevalence, complications, and mortality rate of
      diabetes are rapidly increasing. However, investigations on the actual condition
      of diabetes management are very limited due to lack of nation-wide research or
      multicenter study. Hence, we have minutely inquired the current status of
      diabetes management and achievement of glucose target goal in general hospital
      offering education program. That way, we are able to furnish data for policy
      making of diabetes education and draw up guideline which may allow us to reduce
      the morbidity and mortality of diabetes. METHODS: The subjects consisted of 2,610
      patients with type 2 diabetes who visited the 13 general hospital in Seoul or
      Gyeonggi region from March 19 to May 29, 2013. General characteristics,
      associated diseases, complications, and management status were investigated.
      RESULTS: The mean age was 61.0+/-11.6 years, body mass index was 25.0+/-3.3
      kg/m(2), and family history of diabetes was 50.5%. The mean duration of diabetes
      was 10.7+/-7.9 years and 53% received education about diabetes. The prevalence of
      hypertension and dyslipidemia were 59.2% and 65.5%, respectively, and 18.3% of
      the subjects were accompanied by liver disease. Diabetic retinopathy appeared in
      31.6%, nephropathy in 28.1%, and neuropathy in 19.9% of the subjects. The mean
      glycosylated hemoglobin (HbA1c) level was 7.3%+/-1.3% and the achieving rate
      based on Korean Diabetes Association guideline (HbA1c <6.5%) was 24.8%, blood
      pressure (130/80 mm Hg or less) was 49.4%, and low density lipoprotein
      cholesterol (<100 mg/dL) was 63.6%. The reaching rate to the target level in four
      parameters (blood glucose, blood pressure, lipids, and body weight) was 7.8%.
      CONCLUSION: The blood glucose control rate was lower than other parameters, and
      the implementation rate of diabetes education was only 53%. Thus more appropriate
      glucose control and systematic diabetes education are imperative.

PMID- 26301193
TI  - Maternal and Neonatal Outcomes in Korean Women with Type 1 and Type 2 Diabetes.
AB  - BACKGROUND: The purpose of this study was to evaluate maternal and neonatal
      outcomes in Korean women with type 1 diabetes and type 2 diabetes. METHODS: We
      performed a retrospective survey of 163 pregnancies in women with type 1 diabetes
      (n=13) and type 2 diabetes (n=150) treated from 2003 to 2010 at Cheil General
      Hospital & Women's Healthcare Center, Korea. We compared maternal characteristics
      as well as maternal and neonatal outcomes between groups. RESULTS: Differences in
      glycosylated hemoglobin between type 1 and type 2 diabetes were not significant.
      Birth weight (3,501+/-689.6 g vs. 3,366+/-531.4 g) and rate of major congenital
      malformations (7.7% vs. 5.6%) were not significantly different. However, women
      with type 1 diabetes had higher rates of preeclampsia (38.5% vs. 8.2%, P=0.006),
      large for gestational age (LGA; 46.2% vs. 20.4%, P=0.004), macrosomia (38.5% vs.
      13.4%, P=0.032), and admission for neonatal care (41.7% vs. 14.8%, P=0.03) than
      women with type 2 diabetes. CONCLUSION: Maternal and neonatal outcomes for women
      with type 1 diabetes were poorer than for women with type 2 diabetes, especially
      preeclampsia, LGA, macrosomia and admission to the neonatal intensive care unit.

PMID- 26301194
TI  - Agreement between Framingham Risk Score and United Kingdom Prospective Diabetes
      Study Risk Engine in Identifying High Coronary Heart Disease Risk in North Indian
      Population.
AB  - BACKGROUND: The aim of the study is to evaluate the concurrence between
      Framingham Risk score (FRS) and United Kingdom Prospective Diabetes Study (UKPDS)
      risk engine in identifying coronary heart disease (CHD) risk in newly detected
      diabetes mellitus patients and to explore the characteristics associated with the
      discrepancy between them. METHODS: A cross-sectional study involving 489 subjects
      newly diagnosed with type 2 diabetes mellitus was conducted. Agreement between
      FRS and UKPDS in classifying patients as high risk was calculated using kappa
      statistic. Subjects with discrepant scores between two algorithms were identified
      and associated variables were determined. RESULTS: The FRS identified 20.9%
      subjects (range, 17.5 to 24.7) as high-risk while UKPDS identified 21.75% (range,
      18.3 to 25.5) as high-risk. Discrepancy was observed in 17.9% (range, 14.7 to
      21.7) subjects. About 9.4% had high risk by UKPDS but not FRS, and 8.6% had high
      risk by FRS but not UKPDS. The best agreement was observed at high-risk threshold
      of 20% for both (kappa=0.463). Analysis showed that subjects having high risk on
      FRS but not UKPDS were elderly females having raised systolic and diastolic blood
      pressure. Patients with high risk on UKPDS but not FRS were males and have high
      glycosylated hemoglobin. CONCLUSION: The FRS and UKPDS (threshold 20%) identified
      different populations as being at high risk, though the agreement between them
      was fairly good. The concurrence of a number of factors (e.g., male sex, low high
      density lipoprotein cholesterol, and smoking) in both algorithms should be
      regarded as increasing the CHD risk. However, longitudinal follow-up is required
      to form firm conclusions.

PMID- 26301195
TI  - Maximal Fat Oxidation Rate during Exercise in Korean Women with Type 2 Diabetes
      Mellitus.
AB  - BACKGROUND: The purpose of this study was to determine the appropriate exercise
      intensity associated with maximum fat oxidation, improvement of body composition,
      and metabolic status in Korean women with type 2 diabetes mellitus (T2DM).
      METHODS: The study included a T2DM group (12 women) and a control group (12
      women). The groups were matched in age and body mass index. The subjects
      performed a graded exercise test on a cycle ergometer to measure their maximal
      fat oxidation (Fatmax). We also measured their body composition, metabolic
      profiles, and mitochondrial DNA (mtDNA). RESULTS: The exercise intensity for
      Fatmax was significantly lower in the T2DM group (34.19% maximal oxygen uptake
      [VO2 max]) than the control group (51.80% VO2 max). Additionally, the rate of fat
      oxidation during exercise (P<0.05) and mtDNA (P<0.05) were significantly lower in
      the T2DM group than the control group. The VO2 max level (P<0.001) and the
      insulin level (P<0.05) were positively correlated with the rate of fat oxidation.
      CONCLUSION: The results of this study suggest lower exercise intensity that
      achieves Fatmax is recommended for improving fat oxidation and enhancing fitness
      levels in Korean women with T2DM. Our data could be useful when considering an
      exercise regimen to improve health and fitness.

PMID- 26301196
TI  - Effects of 6-Month Sitagliptin Treatment on Insulin and Glucagon Responses in
      Korean Patients with Type 2 Diabetes Mellitus.
AB  - BACKGROUND: This study aimed to evaluate the effect of sitagliptin, an oral
      dipeptidyl peptidase-4 inhibitor, on insulin secretion and glucagon suppression
      in Korean subjects with type 2 diabetes mellitus. METHODS: Twenty-four subjects
      underwent a 75-g oral glucose tolerance test (OGTT) before and after 6 months of
      sitagliptin treatment. Sitagliptin, insulin, and sulfonylurea were withdrawn for
      3 days before OGTT to eliminate any acute effects on beta-cell insulin or alpha
      cell glucagon secretion. Venous samples were drawn five times during each OGTT to
      measure plasma glucose, insulin, and glucagon. Indices on insulin secretion and
      resistance were calculated. RESULTS: Early phase insulin secretion, measured by
      the insulinogenic index significantly increased after 6 months of sitagliptin
      treatment, especially in the higher baseline body mass index group and higher
      baseline glycosylated hemoglobin (HbA1c) group. There were no significant
      differences in the insulin resistance indices before and after sitagliptin
      treatment. Although no significant differences were observed in the absolute
      levels of glucagon and the glucagon-to-insulin ratio, there was a significant
      reduction in the percentile change of glucagon-to-insulin ratio at 30- and 120
      minute during the OGTT. CONCLUSION: Although the HbA1c level did not decrease
      significantly after 6 months of sitagliptin treatment, an increase in insulin
      secretion and reduction in early phase postprandial plasma glucagon-to-insulin
      ratio excursion was confirmed in Korean subjects with type 2 diabetes.

PMID- 26301198
TI  - Letter: Increased Risk of Hospitalization for Heart Failure with Newly Prescribed
      Dipeptidyl Peptidase-4 Inhibitors and Pioglitazone Using the Korean Health
      Insurance Claims Database (Diabetes Metab J 2015;39:247-52).

PMID- 26301197
TI  - Predictive Factors for Efficacy of Dipeptidyl Peptidase-4 Inhibitors in Patients
      with Type 2 Diabetes Mellitus.
AB  - BACKGROUND: Predictive factors for the efficacy of dipeptidyl peptidase-4 (DPP-4)
      inhibitors for lowering glycosylated hemoglobin (HbA1c) remain unclear in
      patients with type 2 diabetes mellitus. The aim of this study is therefore to
      clarify predictive factors of the efficacy of DPP-4 inhibitors for lowering HbA1c
      after 12 months of treatment. METHODS: A total of 191 consecutive type 2 diabetic
      patients (male sex 55%, mean age, 68.3+/-35.8 years), who had been treated with
      DPP-4 inhibitors for 12 months, were enrolled in this study and evaluated
      retrospectively. RESULTS: After 12 months of DPP-4 inhibitor treatment, random
      blood glucose level, and HbA1c level, decreased from 167+/-63 to 151+/-49 mg/dL
      (P<0.01), and from 7.5%+/-1.3% to 6.9%+/-0.9% (P<0.01) respectively, without
      severe side effects. Multiple regression analysis showed that predictors of DPP-4
      inhibitor treatment efficacy in lowering HbA1c level after 12 months were a
      decrease in HbA1c level after 3 months of treatment, a high baseline HbA1c level,
      a low baseline body mass index, and the absence of coronary artery disease.
      CONCLUSION: Most suitable candidates for treatment with DPP-4 inhibitors are
      diabetics who are not obese and do not have coronary artery disease. In addition,
      long-term efficacy of DPP-4 inhibitors can be predicted by decrement of HbA1c
      after 3 months of treatment.

PMID- 26301199
TI  - Response: Increased Risk of Hospitalization for Heart Failure with Newly
      Prescribed Dipeptidyl Peptidase-4 Inhibitors and Pioglitazone Using the Korean
      Health Insurance Claims Database (Diabetes Metab J 2015;39:247-52).

PMID- 26301200
TI  - Commentary: Vitamin D and Pancreatic Cancer: A Pooled Analysis from the
      Pancreatic Cancer Case-Control Consortium.

PMID- 26301201
TI  - Metastasis: Other Side of the Coin.

PMID- 26301202
TI  - Editorial: Cellular and Phenotypic Plasticity in Cancer.

PMID- 26301203
TI  - Sjogren Syndrome Complicated by Mucosa-Associated Lymphoid Tissue Lymphoma and
      Lymphocytic Interstitial Pneumonia.
AB  - Sjogren syndrome (SS) is an autoimmune disease with exocrine glands dysfunction
      and multiorgan involvement. It is associated with increased risk of
      lymphoproliferative disorders, especially B-cell marginal zone lymphoma. While
      the role of F-18 Fluorodeoxyglucose position emission tomography/computed
      tomography (F-18 FDG PET/CT) for evaluation of lymphoma has been established, its
      use in patients with a chronic history of SS to evaluate for possible
      lymphoproliferative disorders or multiorgan involvement is limited. We present a
      case of chronic SS in which F-18 FDG PET/CT demonstrated FDG avid intraparotid
      and cervical lymph nodes pathologically proven to be mucosa-associated lymphoid
      tissue lymphoma. In addition, the patient had bibasilar cystic changes consistent
      with lymphocytic interstitial pneumonia. 

PMID- 26301205
TI  - Positive Intraoperative Peritoneal Lavage Cytology is a Negative Prognostic
      Factor in Pancreatic Ductal Adenocarcinoma: A Retrospective Single-Center Study.
AB  - OBJECTIVE: The aim of this study is to evaluate the prognostic significance of
      intraoperative peritoneal lavage cytology (PLC) in pancreatic invasive ductal
      adenocarcinoma. METHODS: Intraoperative PLC was evaluated in 162 patients with
      resectable pancreatic invasive ductal adenocarcinoma. The results were analyzed
      for correlations with clinicopathological parameters and/or prognoses. RESULTS:
      In the 162 cases of resectable pancreatic ductal adenocarcinoma, 18 (11%), 141
      (87%), and 3 (2%) were positive, negative, and equivocal for intraoperative PLC,
      respectively. Intraoperative PLC positivity was associated with older patients
      (over 65 years), large tumor size (over 35 mm), tumor location in the body/tail
      of the pancreas, and distant metastasis. Univariate analysis showed that larger
      tumor sizes (>=35 mm, P = 0.001), lymph node metastases (P = 0.005), distant
      metastasis (P = 0.004), advanced stage (stage IIB or III, P = 0.006), advanced
      tumor histological grade (G3, P < 0.001), or positive intraoperative PLC (P =
      0.002) are associated with a shorter survival. Multivariate analysis revealed
      that larger tumor sizes (>=35 mm, P = 0.026), lymph node metastasis (P = 0.021),
      advanced tumor histological grade (G3, P < 0.001), and positive intraoperative
      PLC (P = 0.002) were independent prognostic factors. CONCLUSION: Intraoperative
      PLC is an independent prognostic factor for resectable pancreatic invasive ductal
      adenocarcinoma.

PMID- 26301204
TI  - Immunotherapy of Childhood Sarcomas.
AB  - Pediatric sarcomas are a heterogeneous group of malignant tumors of bone and soft
      tissue origin. Although more than 100 different histologic subtypes have been
      described, the majority of pediatric cases belong to the Ewing's family of
      tumors, rhabdomyosarcoma and osteosarcoma. Most patients that present with
      localized stage are curable with surgery and/or chemotherapy; however, those with
      metastatic disease at diagnosis or those who experience a relapse continue to
      have a very poor prognosis. New therapies for these patients are urgently needed.
      Immunotherapy is an established treatment modality for both liquid and solid
      tumors, and in pediatrics, most notably for neuroblastoma and osteosarcoma. In
      the past, immunomodulatory agents such as interferon, interleukin-2, and
      liposomal-muramyl tripeptide phosphatidyl-ethanolamine have been tried, with some
      activity seen in subsets of patients; additionally, various cancer vaccines have
      been studied with possible benefit. Monoclonal antibody therapies against tumor
      antigens such as disialoganglioside GD2 or immune checkpoint targets such as CTLA
      4 and PD-1 are being actively explored in pediatric sarcomas. Building on the
      success of adoptive T cell therapy for EBV-related lymphoma, strategies to
      redirect T cells using chimeric antigen receptors and bispecific antibodies are
      rapidly evolving with potential for the treatment of sarcomas. This review will
      focus on recent preclinical and clinical developments in targeted agents for
      pediatric sarcomas with emphasis on the immunobiology of immune checkpoints,
      immunoediting, tumor microenvironment, antibody engineering, cell engineering,
      and tumor vaccines. The future integration of antibody-based and cell-based
      therapies into an overall treatment strategy of sarcoma will be discussed. 

PMID- 26301206
TI  - Antibodies against invasive phenotype-specific antigens increase Mycobacterium
      avium subspecies paratuberculosis translocation across a polarized epithelial
      cell model and enhance killing by bovine macrophages.
AB  - Johne's disease, caused by Mycobacterium avium subspecies paratuberculosis (MAP),
      is a severe chronic enteritis which affects large populations of ruminants
      globally. Prevention strategies to combat the spread of Johne's disease among
      cattle herds involve adhering to strict calving practices to ensure young
      susceptible animals do not come in contact with MAP-contaminated colostrum, milk,
      or fecal material. Unfortunately, the current vaccination options available are
      associated with high cost and suboptimal efficacy. To more successfully combat
      the spread of Johne's disease to young calves, an efficient method of protection
      is needed. In this study, we examined passive immunization as a mode of
      introducing protective antibodies against MAP to prevent the passage of the
      bacterium to young animals via colostrum and milk. Utilizing the infectious MAP
      phenotype developed after bacterial exposure to milk, we demonstrate that in
      vitro opsonization with serum from Johne's-positive cattle results in enhanced
      translocation across a bovine MDBK polarized epithelial cell monolayer.
      Furthermore, immune serum opsonization of MAP results in a rapid host cell
      mediated killing by bovine macrophages in an oxidative-, nitrosative-, and
      extracellular DNA trap-independent manner. This study illustrates that antibody
      opsonization of MAP expressing an infectious phenotype leads to the killing of
      the bacterium during the initial stage of macrophage infection. 

PMID- 26301207
TI  - Blood-Brain Barrier Permeability in Aging and Alzheimer's Disease.

PMID- 26301208
TI  - A comparative study on the location of the mandibular foramen in CBCT of normal
      occlusion and skeletal class II and III malocclusion.
AB  - BACKGROUND: During the orthognathic surgery, it is important to know the exact
      anatomical location of the mandibular foramen to achieve successful anesthesia of
      inferior alveolar nerve and to prevent damage to the nerves and vessels supplying
      the mandible. METHODS: Cone-beam computed tomography (CBCT) was used to determine
      the location of the mandibular foramen in 100 patients: 30 patients with normal
      occlusion (13 men, 17 women), 40 patients with skeletal class II malocclusion (15
      men, 25 women), 30 patients with skeletal class III malocclusion (17 men, 13
      women). RESULTS: The distance from the anterior border of the mandibular ramus to
      mandibular foramen did not differ significantly among the three groups, but in
      the group with skeletal class III malocclusion, this distance was an average of
      1.43 +/- 1.95 mm longer in the men than in the women (p < 0.05). In the skeletal
      class III malocclusion group, the mandibular foramen was higher than in the other
      two groups and was an average of 1.85 +/- 3.23 mm higher in the men than in the
      women for all three groups combined (p < 0.05). The diameter of the ramus did not
      differ significantly among the three groups but was an average of 1.03 +/- 2.58
      mm wider in the men than in the women for all three groups combined (p < 0.05).
      In the skeletal class III malocclusion group, the ramus was longer than in the
      other groups and was an average of 7.9 +/- 3.66 mm longer in the men than women.
      CONCLUSIONS: The location of the mandibular foramen was higher in the skeletal
      class III malocclusion group than in the other two groups, possibly because the
      ramus itself was longer in this group. This information should improve the
      success rate for inferior alveolar nerve anesthesia and decrease the
      complications that attend orthognathic surgery.

PMID- 26301209
TI  - A Review of Nutritional Guidelines and Menu Compositions for School Feeding
      Programs in 12 Countries.
AB  - STUDY OBJECTIVES: To analyze the nutritional guidelines and menu compositions of
      school meal provision in various different countries. BACKGROUND: School feeding
      is the provision of food on-site or to take home, which aims to increase school
      enrollment, attendance and retention, and exist as a social safety net for
      households with very low income. Home-grown school feeding, additionally, aims to
      stimulate local economies by providing a source of income for local smallholder
      farmers. METHODS: Literature searches using the Ovid MEDLINE databases gathered
      information from in-country stakeholders and accessed the program websites of
      various countries. Nutrient composition of these menus was calculated from
      nutritional guidelines and menu compositions using a nutrition linear programing
      tool. COUNTRY COMPARISONS: School feeding aims differ between countries of each
      income group. The implementation, delivery of service, and nutritional content of
      foods also differ considerably between countries and income groups. In high
      income countries, guidelines and standards have been recommended in an attempt to
      combat rising levels of overweight and obesity, and to model healthier lifestyle
      habits. In low-income countries, there is a gap in terms of guidance on nutrition
      standards and menu composition. CONCLUSION: Provision of evidence-based guidance
      on nutrition standards to middle and low income countries, who have recently
      established or are planning to establish school feeding, has the potential to
      greatly enhance and improve the quality of service and improve the life of
      millions of children worldwide.

PMID- 26301210
TI  - Healthy Team Healthy U: A Prospective Validation of an Evidence-Based Worksite
      Health Promotion and Wellness Platform.
AB  - OBJECTIVE: To evaluate the effects of a research-tested, team-based health
      promotion and wellness program combined with digital technologies and implemented
      in a diverse worksite setting among hospital, clinic, and university employees.
      METHODS: A prospective cohort study of employees completing biometrics and
      questionnaires before and after the initial 12-session wellness program and its
      12-session booster, 1 year later. RESULTS: After both the initial intervention
      and booster, blood pressure and weight were reduced, with greater reductions
      among employees with pre-hypertension and hypertension and those with a body mass
      index >=25. After both the initial intervention and booster, there was a
      significant increase in (1) daily intake of fruit and vegetable servings, (2)
      days/week of >=30 min of exercise, (3) days/week of strength training, and (4)
      levels of moderately vigorous and vigorous daily physical activity. Self-reported
      indices of both depression and work-related stress were reduced, while
      participants reported increased happiness. Post booster, average sleep quality,
      and sleep duration increased among higher risk employees reporting <=6 h of daily
      sleep. Employees reported receiving encouragement from co-workers to engage in
      healthful diet and physical activities, and exercised together more, and
      indicated that they would recommend the program to other employees. Longitudinal
      analysis revealed the durability of the initial intervention outcomes with
      further beneficial effects after the booster. CONCLUSION: A research tested,
      comprehensive team-based health promotion and wellness program, combined with
      digital technologies, improved employee health behaviors, mood, sleep, elements
      of co-worker cohesion, and biometrics among a diverse multi-site workforce.
      Positive program effects were durable, with enhanced results after the booster.

PMID- 26301211
TI  - Mobile Network Data for Public Health: Opportunities and Challenges.
AB  - The ubiquity of mobile phones worldwide is generating an unprecedented amount of
      human behavioral data both at an individual and aggregated levels. The study of
      this data as a rich source of information about human behavior emerged almost a
      decade ago. Since then, it has grown into a fertile area of research named
      computational social sciences with a wide variety of applications in different
      fields such as social networks, urban and transport planning, economic
      development, emergency relief, and, recently, public health. In this paper, we
      briefly describe the state of the art on using mobile phone data for public
      health, and present the opportunities and challenges that this kind of data
      presents for public health. 

PMID- 26301212
TI  - An Investigation into the Role of Coping in Preventing Depression Associated with
      Perfectionism in Preadolescent Children.
AB  - The relationships between self-oriented and socially prescribed perfectionism
      (SPP) and maladaptive and adaptive coping strategies and their collective impact
      on depression symptoms were examined in the context of a randomized controlled
      universal trial of the Aussie Optimism Positive Thinking Skills Program. Five
      hundred and forty-one children aged 8-12 completed a battery of self-reports, of
      which responses for measures of depression symptoms, perfectionism, and coping
      strategies were examined for the purposes of this study. Structural equation
      modeling tested whether coping mediated the effects of perfectionism on
      depression. Results indicated that SPP had both a direct and an indirect
      relationship with depression symptoms through a moderate association with
      maladaptive coping. Implications for prevention of depression were discussed and
      recommendations for future research were proposed. 

PMID- 26301213
TI  - Risk Factors and Current Health-Seeking Patterns of Migrants in Northeastern
      Mexico: Healthcare Needs for a Socially Vulnerable Population.
AB  - This study identified risk factors for health and access to healthcare services
      of migrants during their journey across Mexico to the United States. Data were
      collected in shelters located in Monterrey, the largest city of northeastern
      Mexico, through a basic clinical examination and a survey completed by 75
      migrants; 92% of them were undocumented Central Americans. During their transit,
      they are at a high risk of contracting, developing, and transmitting diseases.
      The need of working to survive affects health-seeking behavior and a constant
      fear of being traced keeps migrants away from public health services, which
      delays diagnosis and treatment of diseases. Negligent lifestyles, such as
      smoking, drinking (31.8% of men and 11.1% of women), and drug abuse (13% of men
      and 11% of women), were found. Regarding tuberculosis (TB), undocumented migrants
      are usually not screened, even though they come from countries with a high TB
      burden. Besides, they might be overexposed to TB because of their living
      conditions in overcrowded places with deficient hygiene, protection, and
      malnutrition (54.7% of the sample). Possible comorbidities like acquired immune
      deficiency syndrome (AIDS; 4%) and diabetes (2.7%, but probably under-diagnosed)
      were referred. Migrants have little TB knowledge, which is independent of their
      level of education or a previous experience of deportation. About one-third of
      the migrants were totally unfamiliar with TB-related symptoms, while 36% had
      correct knowledge of basic TB symptoms. We conclude that a shortage of
      information on the highly vulnerable migratory population combined with a lack of
      social support and health education among migrants may play a significant role in
      the spread of communicable diseases. We recommend that health authorities address
      this urgent, binational, public health concern in order to prevent outbreaks of
      emerging infections. 

PMID- 26301214
TI  - Making Patients Pay: Informal Patient Payments in Central and Eastern European
      Countries.

PMID- 26301215
TI  - Commentary: Questioning the HIV-AIDS Hypothesis: 30 Years of Dissent.

PMID- 26301217
TI  - Building Better Environmental Risk Assessments.
AB  - Risk assessment is a reasoned, structured approach to address uncertainty based
      on scientific and technical evidence. It forms the foundation for regulatory
      decision-making, which is bound by legislative and policy requirements, as well
      as the need for making timely decisions using available resources. In order to be
      most useful, environmental risk assessments (ERAs) for genetically modified (GM)
      crops should provide consistent, reliable, and transparent results across all
      types of GM crops, traits, and environments. The assessments must also separate
      essential information from scientific or agronomic data of marginal relevance or
      value for evaluating risk and complete the assessment in a timely fashion.
      Challenges in conducting ERAs differ across regulatory systems - examples are
      presented from Canada, Malaysia, and Argentina. One challenge faced across the
      globe is the conduct of risk assessments with limited resources. This challenge
      can be overcome by clarifying risk concepts, placing greater emphasis on data
      critical to assess environmental risk (for example, phenotypic and plant
      performance data rather than molecular data), and adapting advances in risk
      analysis from other relevant disciplines. 

PMID- 26301216
TI  - Nanomaterials in consumer products: a challenging analytical problem.
AB  - Many products used in everyday life are made with the assistance of
      nanotechnologies. Cosmetic, pharmaceuticals, sunscreen, powdered food are only
      few examples of end products containing nano-sized particles (NPs), generally
      added to improve the product quality. To evaluate correctly benefits vs. risks of
      engineered nanomaterials and consequently to legislate in favor of consumer's
      protection, it is necessary to know the hazards connected with the exposure
      levels. This information implies transversal studies and a number of different
      competences. On analytical point of view the identification, quantification and
      characterization of NPs in food matrices and in cosmetic or personal care
      products pose significant challenges, because NPs are usually present at low
      concentration levels and the matrices, in which they are dispersed, are complexes
      and often incompatible with analytical instruments that would be required for
      their detection and characterization. This paper focused on some analytical
      techniques suitable for the detection, characterization and quantification of NPs
      in food and cosmetics products, reports their recent application in
      characterizing specific metal and metal-oxide NPs in these two important
      industrial and market sectors. The need of a characterization of the NPs as much
      as possible complete, matching complementary information about different metrics,
      possible achieved through validate procedures, is what clearly emerges from this
      research. More work should be done to produce standardized materials and to set
      up methodologies to determine number-based size distributions and to get
      quantitative date about the NPs in such a complex matrices. 

PMID- 26301218
TI  - Musculoskeletal Modeling of the Lumbar Spine to Explore Functional Interactions
      between Back Muscle Loads and Intervertebral Disk Multiphysics.
AB  - During daily activities, complex biomechanical interactions influence the
      biophysical regulation of intervertebral disks (IVDs), and transfers of
      mechanical loads are largely controlled by the stabilizing action of spine
      muscles. Muscle and other internal forces cannot be easily measured directly in
      the lumbar spine. Hence, biomechanical models are important tools for the
      evaluation of the loads in those tissues involved in low-back disorders. Muscle
      force estimations in most musculoskeletal models mainly rely, however, on inverse
      calculations and static optimizations that limit the predictive power of the
      numerical calculations. In order to contribute to the development of predictive
      systems, we coupled a predictive muscle model with the passive resistance of the
      spine tissues, in a L3-S1 musculoskeletal finite element model with osmo
      poromechanical IVD descriptions. The model included 46 fascicles of the major
      back muscles that act on the lower spine. The muscle model interacted with
      activity-related loads imposed to the osteoligamentous structure, as standing
      position and night rest were simulated through distributed upper body mass and
      free IVD swelling, respectively. Calculations led to intradiscal pressure values
      within ranges of values measured in vivo. Disk swelling led to muscle activation
      and muscle force distributions that seemed particularly appropriate to
      counterbalance the anterior body mass effect in standing. Our simulations pointed
      out a likely existence of a functional balance between stretch-induced muscle
      activation and IVD multiphysics toward improved mechanical stability of the
      lumbar spine understanding. This balance suggests that proper night rest
      contributes to mechanically strengthen the spine during day activity. 

PMID- 26301219
TI  - A Comparison of the Microbial Production and Combustion Characteristics of Three
      Alcohol Biofuels: Ethanol, 1-Butanol, and 1-Octanol.
AB  - Over the last decade, microbes have been engineered for the manufacture of a
      variety of biofuels. Saturated linear-chain alcohols have great potential as
      transport biofuels. Their hydrocarbon backbones, as well as oxygenated content,
      confer combustive properties that make it suitable for use in internal combustion
      engines. Herein, we compared the microbial production and combustion
      characteristics of ethanol, 1-butanol, and 1-octanol. In terms of productivity
      and efficiency, current microbial platforms favor the production of ethanol. From
      a combustion standpoint, the most suitable fuel for spark-ignition engines would
      be ethanol, while for compression-ignition engines it would be 1-octanol.
      However, any general conclusions drawn at this stage regarding the most superior
      biofuel would be premature, as there are still many areas that need to be
      addressed, such as large-scale purification and pipeline compatibility. So far,
      the difficulties in developing and optimizing microbial platforms for fuel
      production, particularly for newer fuel candidates, stem from our poor
      understanding of the myriad biological factors underpinning them. A great deal of
      attention therefore needs to be given to the fundamental mechanisms that govern
      biological processes. Additionally, research needs to be undertaken across a wide
      range of disciplines to overcome issues of sustainability and commercial
      viability. 

PMID- 26301220
TI  - Repression of CD24 surface protein expression by oncogenic Ras is relieved by
      inhibition of Raf but not MEK or PI3K.
AB  - CD24 is a dynamically regulated cell surface protein. High expression of CD24
      leads to progression of lung, prostrate, colon, and pancreatic cancers, among
      others. In contrast, low expression of CD24 leads to cell proliferation and
      metastasis of breast cancer stem cells (BCSCs). Activating mutations in Ras are
      found in 30% of all human cancers. Oncogenic Ras constitutively stimulates the
      Raf, PI3K, and Ral GDS signaling pathways, leading to cellular transformation.
      Previous studies have shown that expression of oncogenic Ras in breast cancer
      cells generates CD24(-) cells from CD24(+) cells. However, the molecular
      mechanisms involved in the generation of CD24(-) cells were not determined. Here,
      we demonstrate that oncogenic Ras (RasV12) expression suppresses CD24 mRNA,
      protein, and promoter levels when expressed in NIH/3T3 cells. Furthermore,
      activation of only the Raf pathway was sufficient to downregulate CD24 mRNA and
      protein expression to levels similar to those seen in with RasV12 expression. In
      contrast, activation of the PI3K pathway downregulated mRNA expression with a
      partial effect on protein expression whereas activation of the RalGDS pathway
      only partially affected protein expression. Surprisingly, inhibition of MEK with
      U0126 only partially restored CD24 mRNA expression but not surface protein
      expression. In contrast, inhibition of Raf with sorafenib did not restore CD24
      mRNA expression but significantly increased the proportion of RasV12 cells
      expressing CD24. Therefore, the Raf pathway is the major repressor of CD24 mRNA
      and protein expression, with PI3K also able to substantially inhibit CD24
      expression. Moreover, these data indicate that the levels of CD24 mRNA and
      surface protein are independently regulated. Although inhibition of Raf by
      sorafenib only partially restored CD24 expression, sorafenib should still be
      considered as a potential therapeutic strategy to alter CD24 expression in CD24(
      ) cells, such as BCSCs. 

PMID- 26301221
TI  - The Granulocyte-colony stimulating factor has a dual role in neuronal and
      vascular plasticity.
AB  - Granulocyte-colony stimulating factor (G-CSF) is a growth factor that has
      originally been identified several decades ago as a hematopoietic factor required
      mainly for the generation of neutrophilic granulocytes, and is in clinical use
      for that. More recently, it has been discovered that G-CSF also plays a role in
      the brain as a growth factor for neurons and neural stem cells, and as a factor
      involved in the plasticity of the vasculature. We review and discuss these dual
      properties in view of the neuroregenerative potential of this growth factor. 

PMID- 26301223
TI  - Alteration of Fatty Acid Oxidation in Tubular Epithelial Cells: From Acute Kidney
      Injury to Renal Fibrogenesis.
AB  - Renal proximal tubular cells are the most energy-demanding cells in the body. The
      ATP that they use is mostly produced in their mitochondrial and peroxisomal
      compartments, by the oxidation of fatty acids. When those cells are placed under
      a biological stress, such as a transient hypoxia, fatty acid oxidation (FAO) is
      shut down for a period of time that outlasts injury, and carbohydrate oxidation
      does not take over. Facing those metabolic constraints, surviving tubular
      epithelial cells exhibit a phenotypic switch that includes cytoskeletal
      rearrangement and production of extracellular matrix proteins, most probably
      contributing to acute kidney injury-induced renal fibrogenesis, thence to the
      development of chronic kidney disease. Here, we review experimental evidence that
      dysregulation of FAO profoundly affects the fate of tubular epithelial cells, by
      promoting epithelial-to-mesenchymal transition, inflammation, and eventually
      interstitial fibrosis. Restoring physiological production of energy is
      undoubtedly a possible therapeutic approach to unlock the mesenchymal
      reprograming of tubular epithelial cells in the kidney. In this respect, the
      benefit of the use of fibrates is uncertain, but new drugs that could
      specifically target this metabolic pathway, and, hopefully, attenuate renal
      fibrosis merit future research. 

PMID- 26301222
TI  - Animal Models, Learning Lessons to Prevent and Treat Neonatal Chronic Lung
      Disease.
AB  - Bronchopulmonary dysplasia (BPD) is a unique injury syndrome caused by prolonged
      injury and repair imposed on an immature and developing lung. The decreased
      septation and decreased microvascular development phenotype of BPD can be
      reproduced in newborn rodents with increased chronic oxygen exposure and in
      premature primates and sheep with oxygen and/or mechanical ventilation. The
      inflammation caused by oxidants, inflammatory agonists, and/or stretch injury
      from mechanical ventilation seems to promote the anatomic abnormalities. Multiple
      interventions targeted to specific inflammatory cells or pathways or targeted to
      decreasing ventilation-mediated injury can substantially prevent the anatomic
      changes associated with BPD in term rodents and in preterm sheep or primate
      models. Most of the anti-inflammatory therapies with benefit in animal models
      have not been tested clinically. None of the interventions that have been tested
      clinically are as effective as anticipated from the animal models. These
      inconsistencies in responses likely are explained by the antenatal differences in
      lung exposures of the developing animals relative to very preterm humans. The
      animals generally have normal lungs while the lungs of preterm infants are
      exposed variably to intrauterine inflammation, growth abnormalities, antenatal
      corticosteroids, and poorly understood effects from the causes of preterm
      delivery. The animal models have been essential for the definition of the
      mediators that can cause a BPD phenotype. These models will be necessary to
      develop and test future-targeted interventions to prevent and treat BPD. 

PMID- 26301224
TI  - Presence of Anti-Glomerular Basement Membrane Antibodies and Myeloperoxidase Anti
      Neutrophilic Cytoplasmic Antibodies in a Case of Rapidly Progressive
      Glomerulonephritis.
AB  - A 69-year-old male had initially presented with low-grade proteinuria,
      microhematuria, and a positive myeloperoxidase anti-neutrophilic antibody (ANCA).
      He subsequently developed deterioration of kidney function and developed uremic
      symptoms. Creatinine was 486.2 MUmol/L (5.5 mg/dL). Anti-MPO was positive (titer
      >8 U, normal <0.4). He was clinically diagnosed with rapidly proliferative
      glomerulonephritis most likely due to ANCA vasculitis. He received three doses of
      pulse methylprednisolone therapy. Kidney biopsy showed pauci-immune
      glomerulonephritis. Immunofluorescence was positive for faint linear IgG staining
      of glomerular basement membrane (GBM). Anti-GBM antibody was positive 2.1 U
      (normal <1). He was started on high-dose oral steroids; monthly intravenous
      cyclophosphamide and plasmapheresis were also initiated. His symptoms improved
      and creatinine is 247.5 MUmol/L (2.8 mg/dL). His repeat anti-GBM antibody was
      negative. This is a rare case of rapidly progressive glomerulonephritis due to
      dual MPO-ANCA antibodies and anti-GBM antibodies (DAV). 

PMID- 26301225
TI  - Longitudinal omics modeling and integration in clinical metabonomics research:
      challenges in childhood metabolic health research.
AB  - Systems biology is an important approach for deciphering the complex processes in
      health maintenance and the etiology of metabolic diseases. Such integrative
      methodologies will help better understand the molecular mechanisms involved in
      growth and development throughout childhood, and consequently will result in new
      insights about metabolic and nutritional requirements of infants, children and
      adults. To achieve this, a better understanding of the physiological processes at
      anthropometric, cellular and molecular level for any given individual is needed.
      In this respect, novel omics technologies in combination with sophisticated data
      modeling techniques are key. Due to the highly complex network of influential
      factors determining individual trajectories, it becomes imperative to develop
      proper tools and solutions that will comprehensively model biological information
      related to growth and maturation of our body functions. The aim of this review
      and perspective is to evaluate, succinctly, promising data analysis approaches to
      enable data integration for clinical research, with an emphasis on the
      longitudinal component. Approaches based on empirical and mechanistic modeling of
      omics data are essential to leverage findings from high dimensional omics
      datasets and enable biological interpretation and clinical translation. On the
      one hand, empirical methods, which provide quantitative descriptions of patterns
      in the data, are mostly used for exploring and mining datasets. On the other
      hand, mechanistic models are based on an understanding of the behavior of a
      system's components and condense information about the known functions, allowing
      robust and reliable analyses to be performed by bioinformatics pipelines and
      similar tools. Herein, we will illustrate current examples, challenges and
      perspectives in the applications of empirical and mechanistic modeling in the
      context of childhood metabolic health research. 

PMID- 26301227
TI  - New skin closure system facilitates wound healing after cardiovascular
      implantable electronic device surgery.
AB  - The manuscript describes the efficacy of a new skin closure system (ZipLineTM)
      for wound closure after pacemaker/implantable cardioverter defibrillator surgery.
      The system is particularly useful when wound healing is difficult with
      traditional methods and in patients at high risk for surgical site infections
      (SSIs). This skin closure option is easy and quick to apply and remove, and
      produces excellent cosmetic results. Although it is associated with a minimal
      expense upcharge, the benefits, including the potential for decrease in SSI, make
      it attractive and worth considering for skin closure in device patients,
      particularly those at increased risk of complications. 

PMID- 26301226
TI  - Computational approaches for inferring the functions of intrinsically disordered
      proteins.
AB  - Intrinsically disordered proteins (IDPs) are ubiquitously involved in cellular
      processes and often implicated in human pathological conditions. The critical
      biological roles of these proteins, despite not adopting a well-defined fold,
      encouraged structural biologists to revisit their views on the protein structure
      function paradigm. Unfortunately, investigating the characteristics and
      describing the structural behavior of IDPs is far from trivial, and inferring the
      function(s) of a disordered protein region remains a major challenge.
      Computational methods have proven particularly relevant for studying IDPs: on the
      sequence level their dependence on distinct characteristics determined by the
      local amino acid context makes sequence-based prediction algorithms viable and
      reliable tools for large scale analyses, while on the structure level the in
      silico integration of fundamentally different experimental data types is
      essential to describe the behavior of a flexible protein chain. Here, we offer an
      overview of the latest developments and computational techniques that aim to
      uncover how protein function is connected to intrinsic disorder. 

PMID- 26301228
TI  - Fractional flow reserve: Current applications and overview of the available data.
AB  - Flow fractional reserve (FFR) allows to evaluate the functional significance of
      coronary artery lesions, through the ratio of the mean coronary artery pressure
      after the stenosis to the mean aortic pressure during maximum hyperemia. The
      actual widely accepted cut-off value is 0.80. Below this value a coronary lesion
      is considered significant and therefore it requires invasive revascularization.
      Several studies [in particular Fractional Flow Reserve vs Angiography for
      Multivessel Evaluation 1 (FAME-1) and FAME-2] have shown the relationship between
      FFR measurement and hard end-points (death, myocardial infarction, and urgent
      revascularization). Consequently, FFR evaluation represents the cornerstone in
      the decision-making in intermediate coronary lesions. Recent studies paved the
      way for further applications of FFR evaluation in complex and tricky clinical
      settings. In this paper, we perform an overview of the data regarding
      contemporary application of FFR. In particular, we review the use of FFR in: left
      main intermediate stenoses, serial stenoses, evaluation after stenting, guidance
      in coronary artery bypass surgery, and acute coronary syndrome. All the data
      presented in our overview confirm the essential role of FFR assessment in the
      daily clinical practice. The shift from "operator-dependent" to "FFR-dependent"
      evaluation in intermediate coronary artery stenosis is of paramount importance in
      order to improve the prognosis of our patients, through the discrimination of the
      functional role of every single coronary stenosis. 

PMID- 26301229
TI  - Depressive symptoms in neurodegenerative diseases.
AB  - Depressive symptoms are very common in chronic conditions. This is true so for
      neurodegenerative diseases. A number of patients with cognitive decline and
      dementia due to Alzheimer's disease and related conditions like Parkinson's
      disease, Lewy body disease, vascular dementia, frontotemporal degeneration
      amongst other entities, experience depressive symptoms in greater or lesser grade
      at some point during the course of the illness. Depressive symptoms have a
      particular significance in neurological disorders, specially in neurodegenerative
      diseases, because brain, mind, behavior and mood relationship. A number of
      patients may develop depressive symptoms in early stages of the neurologic
      disease, occurring without clear presence of cognitive decline with only mild
      cognitive deterioration. Classically, depression constitutes a reliable
      diagnostic challenge in this setting. However, actually we can recognize and
      evaluate depressive, cognitive or motor symptoms of neurodegenerative disease in
      order to establish their clinical significance and to plan some therapeutic
      strategies. Depressive symptoms can appear also lately, when the
      neurodegenerative disease is fully developed. The presence of depression and
      other neuropsychiatric symptoms have a negative impact on the quality-of-life of
      patients and caregivers. Besides, patients with depressive symptoms also tend to
      further decrease function and reduce cognitive abilities and also uses to present
      more affected clinical status, compared with patients without depression.
      Depressive symptoms are treatable. Early detection of depressive symptoms is very
      important in patients with neurodegenerative disorders, in order to initiate the
      most adequate treatment. We review in this paper the main neurodegenerative
      diseases, focusing in depressive symptoms of each other entities and current
      recommendations of management and treatment. 

PMID- 26301230
TI  - Targeting chronic lymphocytic leukemia cells in the tumor microenviroment: A
      review of the in vitro and clinical trials to date.
AB  - Chronic lymphocytic leukemia (CLL) is the most common leukemia in the western
      world. Despite significant advances in therapy over the last decade CLL remains
      incurable. Current front-line therapy often consists of chemoimmunotherapy-based
      regimens, most commonly the fludarabine, cyclophosphamide plus rituximab
      combination, but rates of relapse and refractory disease are high among these
      patients. Several key signaling pathways are now known to mediate the survival
      and proliferation of CLL cells in vivo, the most notable of which are the
      pathways mediated by the B-cell receptor (BCR) and cytokine receptors. A better
      understanding of the pathogenesis of the disease, the underlying biology of the
      CLL-cell and the roles of the tumour microenvironment has provided the rationale
      for trials of a range of novel, more targeted therapeutic agents. In particular,
      clinical trials of ibrutinib and idelalisib, which target the Brutons tyrosine
      kinase and the delta isoform of phosphoinositol-3 kinase components of the BCR
      signaling pathway respectively, have shown extremely promising results. Here we
      review the current literature on the key signaling pathways and interactions of
      CLL cells that mediate the survival and proliferation of the leukemic cells. For
      each we describe the results of the recent clinical trials and in vitro studies
      of novel therapeutic agents. 

PMID- 26301232
TI  - Intestinal obstruction due to phytobezoars: An update.
AB  - The term bezoar refers to an intraluminal mass in the gastrointestinal system
      caused by the accumulation of indigestible ingested materials, such as
      vegetables, fruits, and hair. Bezoars are responsible for 0.4%-4% of cases of
      mechanical intestinal obstruction. The clinical findings of bezoar-induced ileus
      do not differ from those of mechanical intestinal obstruction due to other
      causes. The appearance and localization of bezoars can be established with
      various imaging methods. Treatment of choice depends on the localization of the
      bezoar which makes the clinical findings. 

PMID- 26301233
TI  - T-lymphoblastic lymphoma with cutaneous involvement.
AB  - To study dermatological manifestation of T-lymphoblastic lymphoma and to help
      clinicians in the diagnosis, we report here the case of a 75-year-old patient who
      presented with violaceous nodules acquired during the last 4 wk and affecting the
      scalp and right arm. The diagnosis of systemic lymphoma was suggested upon the
      appearance of cutaneous tumors, palpable lymph nodes and general symptoms
      including asthenia and weight-loss. The pathology features: positive
      immunostaining for CD3 and terminal deoxynucleotidyl transferase (TdT) and
      staging, led us to the final diagnosis of T-lymphoblastic lymphoma (T-LBL) with
      cutaneous involvement. He received a CHOP regimen as first-line treatment.
      Unfortunately, the patient relapsed and died 8 mo after the treatment initiation.
      T-LBL may be diagnosed by skin lesions. Additional immunostaining including TdT
      and experienced histopathologists are needed to correctly classify this
      aggressive disease and discuss the correct management including bone-marrow
      transplantation where appropriate. 

PMID- 26301234
TI  - Incarceration of Meckel's diverticulum in a left paraduodenal Treitz' hernia.
AB  - Meckel's diverticula incarcerated in a hernia were first described anecdotally by
      Littre, a French surgeon, in 1700. Meckel, a German anatomist and surgeon,
      explained the pathophysiology of this disease 100 years later. In addition, a
      congenital paraduodenal mesocolic hernia, known as a Treitz hernia, is a rare
      cause of small bowel obstruction. These hernias are caused by an abnormal
      rotation of the primitive midgut, resulting in a right or left paraduodenal
      hernia. We treated a patient presenting with pain and diagnosed extraluminal air
      in the abdomen after a computed tomography examination. We performed a laparotomy
      and found a combination of these two seldomly occurring congenital diseases,
      incarceration and perforation of Meckel's diverticulum in a left paraduodenal
      hernia. We performed a thorough review of the literature, and this report is the
      first to describe a patient with a combination of these two rare conditions. We
      considered the case regarding the variety of terminology as well as the treatment
      options of these conditions. 

PMID- 26301231
TI  - Ventricular repolarization markers for predicting malignant arrhythmias in
      clinical practice.
AB  - Malignant cardiac arrhythmias which result in sudden cardiac death may be present
      in individuals apparently healthy or be associated with other medical conditions.
      The way to predict their appearance represents a challenge for the medical
      community due to the tragic outcomes in most cases. In the last two decades some
      ventricular repolarization (VR) markers have been found to be useful to predict
      malignant cardiac arrhythmias in several clinical conditions. The corrected QT,
      QT dispersion, Tpeak-Tend, Tpeak-Tend dispersion and Tp-e/QT have been studied
      and implemented in clinical practice for this purpose. These markers are obtained
      from 12 lead surface electrocardiogram. In this review we discuss how these
      markers have demonstrated to be effective to predict malignant arrhythmias in
      medical conditions such as long and short QT syndromes, Brugada syndrome, early
      repolarization syndrome, acute myocardial ischemia, heart failure, hypertension,
      diabetes mellitus, obesity and highly trained athletes. Also the main
      pathophysiological mechanisms that explain the arrhythmogenic predisposition in
      these diseases and the basis for the VR markers are discussed. However, the same
      results have not been found in all conditions. Further studies are needed to
      reach a global consensus in order to incorporate these VR parameters in risk
      stratification of these patients. 

PMID- 26301235
TI  - Rituximab therapy for primary glomerulonephritis: Report on two cases.
AB  - The evidence in the medical literature on the efficacy and safety of rituximab
      therapy for primary glomerulonephritis is limited and controversial. We describe
      two male Caucasian patients with rapidly progressive kidney failure due to
      primary proliferative glomerulonephritis. Both of them received high-dose
      intravenous corticosteroids and oral cyclophosphamide with limited benefit. The
      first patient (hepatitis C virus-negative mixed cryoglobulinemia) underwent
      plasma-exchange with intravenous immunoglobulins; he showed significant benefit
      on kidney function (he became dialysis independent with serum creatinine going
      back to 1.6 mg/dL) after one rituximab pulse even if urinary abnormalities were
      still present. No improvement in renal function or urinary changes occurred in
      the second patient. Both these individuals developed sepsis over the follow-up,
      the first patient died two months after rituximab therapy. This report is in
      keeping with the occurrence of severe infections after rituximab therapy in
      patients with renal impairment at baseline and concomitant high-dose steroids. 

PMID- 26301237
TI  - Combined surgical-orthodontic rehabilitation of cleidocranial dysplasia: 5 years
      follow-up.
AB  - Cleidocranial dysplasia (CD) is an autosomal dominant syndrome which is
      characterized by several skeletal malformations such as non-closed fontanelles,
      skeletal abnormalities of the maxilla and mandible and absence of clavicles. Mid
      facial hypoplasia and mandibular prognathism are mostly seen jaw abnormalities in
      CD. In this study, the combined orthodontic-surgical treatment of a patient with
      CD with class III malocclusion and multiple unerupted primary and deciduous teeth
      is presented. 

PMID- 26301236
TI  - When sepsis affects the heart: A case report and literature review.
AB  - A 59-year-old nursing home patient with Down syndrome was brought to the internal
      medicine department of our hospital due to fever, cough without expectorate, and
      dyspnea. A thoracic computed tomography revealed the presence of bilateral basal
      parenchymal opacities. Her condition deteriorated after admission and troponin
      reached a peak serum concentration of 16.9 ng/mL. The patient was in cardiogenic
      shock. In addition to fluid resuscitation, vaso-active amine infusion was
      administered to achieve hemodynamic stabilization. The differential diagnosis
      investigated possible pulmonary embolism, myocardial infarction, and myocarditis.
      Furthermore, a second transthoracic echocardiogram suggested Tako-Tsubo syndrome.
      This is a septic patient. The purpose of this manuscript is to review studies
      which formerly examined the possible association between high levels of troponin
      and mortality to see if it can be considered a positive predictive factor of
      fatal prognosis as the case of thrombocytopenia, already a positive independent
      predictive factor of multiple organ failure syndrome, and generally to
      characterize risk profile in a septic patient. 

PMID- 26301238
TI  - Dichloroacetate Decreases Cell Health and Activates Oxidative Stress Defense
      Pathways in Rat Alveolar Type II Pneumocytes.
AB  - Dichloroacetate (DCA) is a water purification byproduct that is known to be
      hepatotoxic and hepatocarcinogenic and to induce peripheral neuropathy and damage
      macrophages. This study characterizes the effects of the haloacetate on lung
      cells by exposing rat alveolar type II (L2) cells to 0-24 mM DCA for 6-24 hours.
      Increasing DCA concentration and the combination of increasing DCA concentration
      plus longer exposures decrease measures of cellular health. Length of exposure
      has no effect on oxidative stress biomarkers, glutathione, SOD, or CAT.
      Increasing DCA concentration alone does not affect total glutathione or its redox
      ratio but does increase activity in the SOD/CAT oxidative stress defense pathway.
      These data suggest that alveolar type II cells rely on SOD and CAT more than
      glutathione to combat DCA-induced stress.

PMID- 26301239
TI  - Corrigendum to "Evaluation of Candida Colonization and Specific Humoral Responses
      against Candida albicans in Patients with Atopic Dermatitis".

PMID- 26301241
TI  - Patient-Specific CT-Based Instrumentation versus Conventional Instrumentation in
      Total Knee Arthroplasty: A Prospective Randomized Controlled Study on Clinical
      Outcomes and In-Hospital Data.
AB  - Total knee arthroplasty (TKA) is a frequently performed procedure in orthopaedic
      surgery. Recently, patient-specific instrumentation was introduced to facilitate
      correct positioning of implants. The aim of this study was to compare the early
      clinical results of TKA performed with patient-specific CT-based instrumentation
      and conventional technique. A prospective, randomized controlled trial on 112
      patients was performed between January 2011 and December 2011. A group of 112
      patients who met the inclusion and exclusion criteria were enrolled in this study
      and randomly assigned to an experimental or control group. The experimental group
      comprised 52 patients who received the Signature CT-based implant positioning
      system, and the control group consisted of 60 patients with conventional
      instrumentation. Clinical outcomes were evaluated with the KSS scale, WOMAC
      scale, and VAS scales to assess knee pain severity and patient satisfaction with
      the surgery. Specified in-hospital data were recorded. Patients were followed up
      for 12 months. At one year after surgery, there were no statistically significant
      differences between groups with respect to clinical outcomes and in-hospital
      data, including operative time, blood loss, hospital length of stay,
      intraoperative observations, and postoperative complications. Further high
      quality investigations of various patient-specific systems and longer follow-up
      may be helpful in assessing their utility for TKA. 

PMID- 26301242
TI  - Microbiological Analysis of Necrosols Collected from Urban Cemeteries in Poland.
AB  - Decomposition of organic matter is the primary function in the soil ecosystem,
      which involves bacteria and fungi. Soil microbial content depends on many
      factors, and secondary biological and chemical contaminations change and affect
      environmental feedback. Little work has been done to estimate the microbiological
      risk for cemetery employees and visitors. The potential risk of infection for
      people in the cemetery is primarily associated with injury and wound
      contamination during performing the work. The aim of this study was to analyze
      the microbiota of cemetery soil obtained from cemeteries and bacterial
      composition in selected soil layers encountered by gravediggers and cemetery
      caretakers. The most common bacterial pathogens were Enterococcus spp. (80.6%),
      Bacillus spp. (77.4%), and E. coli (45.1%). The fungi Penicillium spp. and
      Aspergillus spp. were isolated from 51% and 6.4% of samples, respectively. Other
      bacterial species were in the ground cemetery relatively sparse. Sampling depth
      was not correlated with bacterial growth (p > 0.05), but it was correlated with
      several differences in microbiota composition (superficial versus deep layer). 

PMID- 26301240
TI  - Omega-3 Polyunsaturated Fatty Acids: The Way Forward in Times of Mixed Evidence.
AB  - Almost forty years ago, it was first hypothesized that an increased dietary
      intake of omega-3 polyunsaturated fatty acids (PUFA) from fish fat could exert
      protective effects against several pathologies. Decades of intense preclinical
      investigation have supported this hypothesis in a variety of model systems.
      Several clinical cardiovascular studies demonstrated the beneficial health
      effects of omega-3 PUFA, leading medical institutions worldwide to publish
      recommendations for their increased intake. However, particularly in recent
      years, contradictory results have been obtained in human studies focusing on
      cardiovascular disease and the clinical evidence in other diseases, particularly
      chronic inflammatory and neoplastic diseases, was never established to a degree
      that led to clear approval of treatment with omega-3 PUFA. Recent data not in
      line with the previous findings have sparked a debate on the health efficacy of
      omega-3 PUFA and the usefulness of increasing their intake for the prevention of
      a number of pathologies. In this review, we aim to examine the controversies on
      the possible use of these fatty acids as preventive/curative tools against the
      development of cardiovascular, metabolic, and inflammatory diseases, as well as
      several kinds of cancer. 

PMID- 26301243
TI  - Omega-3 Fatty Acids in Early Prevention of Inflammatory Neurodegenerative
      Disease: A Focus on Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is the leading cause of dementia and the most common
      neurodegenerative disease in the elderly. Furthermore, AD has provided the most
      positive indication to support the fact that inflammation contributes to
      neurodegenerative disease. The exact etiology of AD is unknown, but environmental
      and genetic factors are thought to contribute, such as advancing age, family
      history, presence of chronic diseases such as cardiovascular disease (CVD) and
      diabetes, and poor diet and lifestyle. It is hypothesised that early prevention
      or management of inflammation could delay the onset or reduce the symptoms of AD.
      Normal physiological changes to the brain with ageing include depletion of long
      chain omega-3 fatty acids and brains of AD patients have lower docosahexaenoic
      acid (DHA) levels. DHA supplementation can reduce markers of inflammation. This
      review specifically focusses on the evidence in humans from epidemiological,
      dietary intervention, and supplementation studies, which supports the role of
      long chain omega-3 fatty acids in the prevention or delay of cognitive decline in
      AD in its early stages. Longer term trials with long chain omega-3
      supplementation in early stage AD are warranted. We also highlight the importance
      of overall quality and composition of the diet to protect against AD and
      dementia. 

PMID- 26301244
TI  - Omega-3 PUFAs Lower the Propensity for Arachidonic Acid Cascade Overreactions.
AB  - A productive view of the benefits from omega-3 (n-3) nutrients is that the
      dietary essential omega-6 (n-6) linoleic acid has a very narrow therapeutic
      window which is widened by n-3 nutrients. The benefit from moderate physiological
      actions of the arachidonic acid cascade can easily shift to harm from excessive
      pathophysiological actions. Recognizing the factors that predispose the cascade
      to an unwanted overactivity gives a rational approach for arranging beneficial
      interactions between the n-3 and n-6 essential nutrients that are initial
      components of the cascade. Much detailed evidence for harmful cascade actions was
      collected by pharmaceutical companies as they developed drugs to decrease those
      actions. A remaining challenge is to understand the factors that predispose the
      cascade toward unwanted outcomes and create the need for therapeutic
      interventions. Such understanding involves recognizing the similar dynamics for
      dietary n-3 and n-6 nutrients in forming the immediate precursors of the cascade
      plus the more vigorous actions of the n-6 precursor, arachidonic acid, in forming
      potent mediators that amplify unwanted cascade outcomes. Tools have been
      developed to aid deliberate day-to-day quantitative management of the propensity
      for cascade overactivity in ways that can decrease the need for drug treatments. 

PMID- 26301245
TI  - Three-Dimensional Modelling inside a Differential Pressure Laminar Flow
      Bioreactor Filled with Porous Media.
AB  - A three-dimensional computational fluid dynamics- (CFD-) model based on a
      differential pressure laminar flow bioreactor prototype was developed to further
      examine performance under changing culture conditions. Cell growth inside
      scaffolds was simulated by decreasing intrinsic permeability values and led to
      pressure build-up in the upper culture chamber. Pressure release by an integrated
      bypass system allowed continuation of culture. The specific shape of the
      bioreactor culture vessel supported a homogenous flow profile and mass flux at
      the scaffold level at various scaffold permeabilities. Experimental data showed
      an increase in oxygen concentration measured inside a collagen scaffold seeded
      with human mesenchymal stem cells when cultured in the perfusion bioreactor after
      24 h compared to static culture in a Petri dish (dynamic: 11% O2 versus static:
      3% O2). Computational fluid simulation can support design of bioreactor systems
      for tissue engineering application.

PMID- 26301246
TI  - Green Tea Increases the Concentration of Total Mercury in the Blood of Rats
      following an Oral Fish Tissue Bolus.
AB  - Fish has many health benefits but is also the most common source of
      methylmercury. The bioavailability of methylmercury in fish may be affected by
      other meal components. In this study, the effect of green tea on the
      bioavailability of methylmercury from an oral bolus of fish muscle tissue was
      studied in rats and compared to a water treated control group and a group treated
      with meso-2,3-dimercaptosuccinic acid (DMSA), a compound used medically to
      chelate mercury. Rats were given a single oral dose of fish tissue via gavage and
      one of the treatments. Rats were given access to food for 3 h at 12 h intervals.
      They were dosed with each of the treatments with each meal. Blood samples were
      collected for 95 hours. Green tea significantly increased the concentration of
      total mercury in blood relative to the control, whereas DMSA significantly
      decreased it. In addition, feeding caused a slight increase in blood mercury for
      several meals following the initial dose.

PMID- 26301247
TI  - Air Pollution by Hydrothermal Volcanism and Human Pulmonary Function.
AB  - The aim of this study was to assess whether chronic exposure to volcanogenic air
      pollution by hydrothermal soil diffuse degassing is associated with respiratory
      defects in humans. This study was carried in the archipelago of the Azores, an
      area with active volcanism located in the Atlantic Ocean where Eurasian, African,
      and American lithospheric plates meet. A cross-sectional study was performed on a
      study group of 146 individuals inhabiting an area where volcanic activity is
      marked by active fumarolic fields and soil degassing (hydrothermal area) and a
      reference group of 359 individuals inhabiting an area without these secondary
      manifestations of volcanism (nonhydrothermal area). Odds ratio (OR) and 95%
      confidence intervals (CIs) were adjusted for age, gender, fatigue, asthma, and
      smoking. The OR for restrictive defects and for exacerbation of obstructive
      defects (COPD) in the hydrothermal area was 4.4 (95% CI 1.78-10.69) and 3.2 (95%
      CI 1.82-5.58), respectively. Increased prevalence of restrictions and all COPD
      severity ranks (mild, moderate, and severe) was observed in the population from
      the hydrothermal area. These findings may assist health officials in advising and
      keeping up with these populations to prevent and minimize the risk of respiratory
      diseases. 

PMID- 26301248
TI  - omega-3 PUFAs and Resveratrol Differently Modulate Acute and Chronic Inflammatory
      Processes.
AB  - omega-3 PUFAs and polyphenols have multiple effects on inflammation in vivo and
      in vitro. The effects of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA),
      and resveratrol (RV) were investigated in LPS-stimulated peripheral blood
      leukocytes (PBLs) (i.e., acute inflammation) and IL-1beta activated human
      chondrocytes (i.e., chronic inflammation). Inflammatory mediators including
      chemokines, cytokines, interleukins, and PGE2 were measured by multiplex analysis
      and gene expression was quantified by RT-PCR. In PBLs, RV decreased the secretion
      of PGE2, CCL5/RANTES, and CXCL8/IL-8 but increased IL-1beta, IL-6, and IL-10. In
      contrast to RV, omega-3 PUFAs augmented the production of PGE2 and CXCL8/IL-8.
      EPA and DHA similarly affected the pattern of inflammatory mediators. Combination
      of RV and omega-3 PUFAs exerted synergistic effects on CCL5/RANTES and had
      additive effects on IL-6 or CXCL8/IL-8. Both omega-3 PUFAs and RV reduced
      catabolic gene expression (e.g., MMPs, ADAMTS-4, IL-1beta, and IL-6) in activated
      chondrocytes. The data suggest that omega-3 PUFAs and RV differ in the regulation
      of acute inflammation of peripheral blood leukocytes but have common properties
      in modulating features related to chronic inflammation of chondrocytes. 

PMID- 26301249
TI  - Evaluation of Ricinus communis L. for the Phytoremediation of Polluted Soil with
      Organochlorine Pesticides.
AB  - Phytoremediation is an attractive alternative to conventional treatments of soil
      due to advantages such as low cost, large application areas, and the possibility
      of in situ treatment. This study presents the assessment of phytoremediation
      processes conducted under controlled experimental conditions to evaluate the
      ability of Ricinus communis L., tropical plant species, to promote the
      degradation of 15 persistent organic pollutants (POPs), in a 66-day period. The
      contaminants tested were hexachlorocyclohexane (HCH), DDT, heptachlor, aldrin,
      and others. Measurements made in rhizosphere soil indicate that the roots of the
      studied species reduce the concentration of pesticides. Results obtained during
      this study indicated that the higher the hydrophobicity of the organic compound
      and its molecular interaction with soil or root matrix the greater its tendency
      to concentrate in root tissues and the research showed the following trend: HCHs
      < diclofop-methyl < chlorpyrifos < methoxychlor < heptachlor epoxide < endrin <
      o,p'-DDE < heptachlor < dieldrin < aldrin < o,p'-DDT < p,p'-DDT by increasing
      order of log K ow values. The experimental results confirm the importance of
      vegetation in removing pollutants, obtaining remediation from 25% to 70%, and
      demonstrated that Ricinus communis L. can be used for the phytoremediation of
      such compounds. 

PMID- 26301250
TI  - The Omega-3 Fatty Acid Docosahexaenoic Acid Modulates Inflammatory Mediator
      Release in Human Alveolar Cells Exposed to Bronchoalveolar Lavage Fluid of ARDS
      Patients.
AB  - BACKGROUND: This study investigated whether the 1 : 2 omega-3/omega-6 ratio may
      reduce proinflammatory response in human alveolar cells (A549) exposed to an ex
      vivo inflammatory stimulus (bronchoalveolar lavage fluid (BALF) of acute
      respiratory distress syndrome (ARDS) patients). Methods. We exposed A549 cells to
      the BALF collected from 12 ARDS patients. After 18 hours, fatty acids (FA) were
      added as docosahexaenoic acid (DHA, omega-3) and arachidonic acid (AA, omega-6)
      in two ratios (1 : 2 or 1 : 7). 24 hours later, in culture supernatants were
      evaluated cytokines (TNF-alpha, IL-6, IL-8, and IL-10) and prostaglandins (PGE2
      and PGE3) release. The FA percentage content in A549 membrane phospholipids,
      content of COX-2, level of PPARgamma, and NF-kappaB binding activity were
      determined. RESULTS: The 1 : 2 DHA/AA ratio reversed the baseline predominance of
      omega-6 over omega-3 in the cell membranes (P < 0.001). The proinflammatory
      cytokine release was reduced by the 1 : 2 ratio (P < 0.01 to <0.001) but was
      increased by the 1 : 7 ratio (P < 0.01). The 1 : 2 ratio reduced COX-2 and PGE2
      (P < 0.001) as well as NF-kappaB translocation into the nucleus (P < 0.01), while
      it increased activation of PPARgamma and IL-10 release (P < 0.001). Conclusion.
      This study demonstrated that shifting the FA supply from omega-6 to omega-3
      decreased proinflammatory mediator release in human alveolar cells exposed to
      BALF of ARDS patients.

PMID- 26301251
TI  - Krill Oil Ameliorates Mitochondrial Dysfunctions in Rats Treated with High-Fat
      Diet.
AB  - In recent years, several studies focused their attention on the role of dietary
      fats in the pathogenesis of hepatic steatosis. It has been demonstrated that a
      high-fat diet is able to induce hyperglycemia, hyperinsulinemia, obesity, and
      nonalcoholic fatty liver disease. On the other hand, krill oil, a novel dietary
      supplement of n-3 PUFAs, has the ability to improve lipid and glucose metabolism,
      exerting possible protective effects against hepatic steatosis. In this study we
      have investigated the effects of krill oil on mitochondrial energetic metabolism
      in animals fed a high-fat diet. To this end, male Sprague-Dawley rats were
      divided into three groups and fed for 4 weeks with a standard diet (control
      group), a diet with 35% fat (HF group), or a high-fat diet supplemented with 2.5%
      krill oil (HF+KO group). The obtained results suggest that krill oil promotes the
      burning of fat excess introduced by the high-fat diet. This effect is obtained by
      stimulating mitochondrial metabolic pathways such as fatty acid oxidation, Krebs
      cycle, and respiratory chain complexes activity. Modulation of the expression of
      carrier proteins involved in mitochondrial uncoupling was also observed. Overall,
      krill oil counteracts the negative effects of a high-fat diet on mitochondrial
      energetic metabolism. 

PMID- 26301252
TI  - Omega-3 Polyunsaturated Fatty Acids: Structural and Functional Effects on the
      Vascular Wall.
AB  - Omega-3 polyunsaturated fatty acids (n-3 PUFA) consumption is associated with
      reduced cardiovascular disease risk. Increasing evidence demonstrating a
      beneficial effect of n-3 PUFA on arterial wall properties is progressively
      emerging. We reviewed the recent available evidence for the cardiovascular
      effects of n-3 PUFA focusing on structural and functional properties of the
      vascular wall. In experimental studies and clinical trials n-3 PUFA have shown
      the ability to improve arterial hemodynamics by reducing arterial stiffness, thus
      explaining some of its cardioprotective properties. Recent studies suggest
      beneficial effects of n-3 PUFA on endothelial activation, which are likely to
      improve vascular function. Several molecular, cellular, and physiological
      pathways influenced by n-3 PUFA can affect arterial wall properties and therefore
      interfere with the atherosclerotic process. Although the relative weight of
      different physiological and molecular mechanisms and the dose-response on
      arterial wall properties have yet to be determined, n-3 PUFA have the potential
      to beneficially impact arterial wall remodeling and cardiovascular outcomes by
      targeting arterial wall stiffening and endothelial dysfunction. 

PMID- 26301253
TI  - Spatially Enhanced Differential RNA Methylation Analysis from Affinity-Based
      Sequencing Data with Hidden Markov Model.
AB  - With the development of new sequencing technology, the entire N6-methyl-adenosine
      (m(6)A) RNA methylome can now be unbiased profiled with methylated RNA immune
      precipitation sequencing technique (MeRIP-Seq), making it possible to detect
      differential methylation states of RNA between two conditions, for example,
      between normal and cancerous tissue. However, as an affinity-based method, MeRIP
      Seq has yet provided base-pair resolution; that is, a single methylation site
      determined from MeRIP-Seq data can in practice contain multiple RNA methylation
      residuals, some of which can be regulated by different enzymes and thus
      differentially methylated between two conditions. Since existing peak-based
      methods could not effectively differentiate multiple methylation residuals
      located within a single methylation site, we propose a hidden Markov model (HMM)
      based approach to address this issue. Specifically, the detected RNA methylation
      site is further divided into multiple adjacent small bins and then scanned with
      higher resolution using a hidden Markov model to model the dependency between
      spatially adjacent bins for improved accuracy. We tested the proposed algorithm
      on both simulated data and real data. Result suggests that the proposed algorithm
      clearly outperforms existing peak-based approach on simulated systems and detects
      differential methylation regions with higher statistical significance on real
      dataset. 

PMID- 26301255
TI  - Pressure modulation algorithm to separate cerebral hemodynamic signals from
      extracerebral artifacts.
AB  - We introduce and validate a pressure measurement paradigm that reduces
      extracerebral contamination from superficial tissues in optical monitoring of
      cerebral blood flow with diffuse correlation spectroscopy (DCS). The scheme
      determines subject-specific contributions of extracerebral and cerebral tissues
      to the DCS signal by utilizing probe pressure modulation to induce variations in
      extracerebral blood flow. For analysis, the head is modeled as a two-layer medium
      and is probed with long and short source-detector separations. Then a combination
      of pressure modulation and a modified Beer-Lambert law for flow enables
      experimenters to linearly relate differential DCS signals to cerebral and
      extracerebral blood flow variation without a priori anatomical information. We
      demonstrate the algorithm's ability to isolate cerebral blood flow during a
      finger-tapping task and during graded scalp ischemia in healthy adults. Finally,
      we adapt the pressure modulation algorithm to ameliorate extracerebral
      contamination in monitoring of cerebral blood oxygenation and blood volume by
      near-infrared spectroscopy. 

PMID- 26301256
TI  - Updated Mechanisms of Sickle Cell Disease-Associated Chronic pain.
AB  - Sickle cell disease (SCD), a hemoglobinopathy, causes sickling of red blood
      cells, resulting in vessel blockage, stroke, anemia, inflammation, and extreme
      pain. A vast majority of SCD patients experience pain on a chronic basis, and
      many turn to opioids to provide limited relief. The side effects that come with
      chronic opioid use push for research into understanding the specific mechanisms
      of SCD-associated chronic pain. Current advances in SCD-associated pain have
      focused on alterations in the pain pathway including nociceptor sensitization and
      endogenous pain inducers. This article reviews the underlying pathophysiology of
      SCD, potential pain mechanisms, current treatments and their mechanism of action,
      and future directions of SCD-associated pain management. The information provided
      could help propel research in SCD-associated chronic pain and uncover novel
      treatment options for clinicians.

PMID- 26301258
TI  - Enhancement of Anaerobic Digestion to Treat Saline Sludge from Recirculating
      Aquaculture Systems.
AB  - The effectiveness of carbohydrate addition and the use of ultrasonication as a
      pretreatment for the mesophilic anaerobic digestion of saline aquacultural sludge
      was assessed. Analyses were conducted using an anaerobic sequencing batch reactor
      (ASBR), which included stopped gas production attributed to the saline
      inhibition. After increasing the C : N ratio, gas production was observed, and
      the total chemical oxygen demand (TCOD) removal efficiency increased from 75% to
      80%. The TCOD removal efficiency of the sonication period was approximately 85%,
      compared to 75% for the untreated waste. Ultrasonication of aquaculture sludge
      was also found to enhance the gas production rate and the TCOD removal
      efficiency. The average volatile fatty acid (VFA) to alkalinity ratios ranged
      from 0.1 to 0.05, confirming the stability of the digesters. Furthermore, soluble
      chemical oxygen demand (SCOD), VFA, and PO4 (3-) concentrations increased in the
      effluents. There was a 114% greater gas generation during the ultrasonication
      period, with an average production of 0.08 g COD/L . day(-1).

PMID- 26301254
TI  - The Role of Cardiolipin in Cardiovascular Health.
AB  - Cardiolipin (CL), the signature phospholipid of mitochondrial membranes, is
      crucial for both mitochondrial function and cellular processes outside of the
      mitochondria. The importance of CL in cardiovascular health is underscored by the
      life-threatening genetic disorder Barth syndrome (BTHS), which manifests
      clinically as cardiomyopathy, skeletal myopathy, neutropenia, and growth
      retardation. BTHS is caused by mutations in the gene encoding tafazzin, the
      transacylase that carries out the second CL remodeling step. In addition to BTHS,
      CL is linked to other cardiovascular diseases (CVDs), including cardiomyopathy,
      atherosclerosis, myocardial ischemia-reperfusion injury, heart failure, and
      Tangier disease. The link between CL and CVD may possibly be explained by the
      physiological roles of CL in pathways that are cardioprotective, including
      mitochondrial bioenergetics, autophagy/mitophagy, and mitogen activated protein
      kinase (MAPK) pathways. In this review, we focus on the role of CL in the
      pathogenesis of CVD as well as the molecular mechanisms that may link CL
      functions to cardiovascular health. 

PMID- 26301259
TI  - Vitamin D Status among Older Adults Residing in the Littoral and Andes Mountains
      in Ecuador.
AB  - OBJECTIVES: To estimate the prevalence of 25-hydroxyvitamin D (25(OH)D)
      deficiency and its determinants among older adults in Ecuador. METHODS: 25(OH)D
      deficiency and insufficiency prevalence rates were examined among participants in
      the National Survey of Health, Wellbeing, and Aging. Logistic regression models
      were used to evaluate demographic characteristics associated with 25(OH)D
      deficiency. RESULTS: Of 2,374 participants with a mean age of 71.0 (8.3) years,
      25(OH)D insufficiency and deficiency were present in 67.8% (95% CI, 65.3-70.2)
      and 21.6% (95% CI, 19.5-23.7) of older adults in Ecuador, respectively. Women
      (OR, 3.19; 95% CI, 3.15-3.22), self-reported race as Indigenous (OR, 2.75; 95%
      CI, 2.70-2.80), and residents in rural (OR, 4.49; 95% CI, 4.40-4.58) and urban
      (OR, 2.74; 95% CI, 2.69-2.80) areas of the Andes Mountains region were variables
      significantly associated with 25(OH)D deficiency among older adults. CONCLUSIONS:
      Despite abundant sunlight throughout the year in Ecuador, 25(OH)D deficiency was
      significantly prevalent among older women, Indigenous subjects, and subjects
      residing in the Andes Mountains region of the country. The present findings may
      assist public health authorities to implement policies of vitamin D
      supplementation among older adults at risk for this condition.

PMID- 26301257
TI  - Defects in NADPH Oxidase Genes NOX1 and DUOX2 in Very Early Onset Inflammatory
      Bowel Disease.
AB  - BACKGROUND & AIMS: Defects in intestinal innate defense systems predispose
      patients to inflammatory bowel disease (IBD). Reactive oxygen species (ROS)
      generated by nicotinamide-adenine dinucleotide phosphate (NADPH) oxidases in the
      mucosal barrier maintain gut homeostasis and defend against pathogenic attack. We
      hypothesized that molecular genetic defects in intestinal NADPH oxidases might be
      present in children with IBD. METHODS: After targeted exome sequencing of
      epithelial NADPH oxidases NOX1 and DUOX2 on 209 children with very early onset
      inflammatory bowel disease (VEOIBD), the identified mutations were validated
      using Sanger Sequencing. A structural analysis of NOX1 and DUOX2 variants was
      performed by homology in silico modeling. The functional characterization
      included ROS generation in model cell lines and in in vivo transduced murine
      crypts, protein expression, intracellular localization, and cell-based infection
      studies with the enteric pathogens Campylobacter jejuni and enteropathogenic
      Escherichia coli. RESULTS: We identified missense mutations in NOX1 (c.988G>A,
      p.Pro330Ser; c.967G>A, p.Asp360Asn) and DUOX2 (c.4474G>A, p.Arg1211Cys;
      c.3631C>T, p.Arg1492Cys) in 5 of 209 VEOIBD patients. The NOX1 p.Asp360Asn
      variant was replicated in a male Ashkenazi Jewish ulcerative colitis cohort. All
      NOX1 and DUOX2 variants showed reduced ROS production compared with wild-type
      enzymes. Despite appropriate cellular localization and comparable pathogen
      stimulated translocation of altered oxidases, cells harboring NOX1 or DUOX2
      variants had defective host resistance to infection with C. jejuni. CONCLUSIONS:
      This study identifies the first inactivating missense variants in NOX1 and DUOX2
      associated with VEOIBD. Defective ROS production from intestinal epithelial cells
      constitutes a risk factor for developing VEOIBD.

PMID- 26301261
TI  - Seeing Past Cellular Adaptation.
AB  - Automated image analysis of unperturbed cells reveals a new sequence of events
      underlying protrusion of the cell membrane.

PMID- 26301260
TI  - Surgical Management of Endometrial Polyps in Infertile Women: A Comprehensive
      Review.
AB  - Endometrial polyps are benign localized lesions of the endometrium, which are
      commonly seen in women of reproductive age. Observational studies have suggested
      a detrimental effect of endometrial polyps on fertility. The natural course of
      endometrial polyps remains unclear. Expectant management of small and
      asymptomatic polyps is reasonable in many cases. However, surgical resection of
      endometrial polyps is recommended in infertile patients prior to treatment in
      order to increase natural conception or assisted reproductive pregnancy rates.
      There is mixed evidence regarding the resection of newly diagnosed endometrial
      polyps during ovarian stimulation to improve the outcomes of fresh in vitro
      fertilization cycles. Hysteroscopy polypectomy remains the gold standard for
      surgical treatment. Evidence regarding the cost and efficacy of different methods
      for hysteroscopic resection of endometrial polyps in the office and outpatient
      surgical settings has begun to emerge. 

PMID- 26301264
TI  - Fabrication and mechanical properties of PLA/HA composites: A study of in vitro
      degradation.
AB  - The adverse effects of stress shielding from the use of high-modulus metallic
      alloy bio-implant materials has led to increased research into developing polymer
      ceramic composite materials that match the elastic modulus of human bone. Of
      particular interest are poly-l-lactic acid- hydroxyapatite (PLA/HA)-based
      composites which are fully resorbable in vivo. However, their bioresorbability
      has a deleterious effect on the mechanical properties of the implant. The purpose
      of this study is to investigate, from a micromechanistic perspective, the in
      vitro degradation behavior of such composites manufactured using a simple hot
      pressing route for two different hydroxyapatite particles: a fine-grained
      (average particle size ~5 MUm) commercial powder or coarser whiskers (~25-30 MUm
      long, ~5 MUm in diameter). We observed that composites with ceramic contents
      ranging between 70 and 85 wt.% have mechanical properties that match reasonably
      those of human cortical bone. However, the properties deteriorate with immersion
      in Hanks' Balanced Salt Solution due to the degradation of the polymer phase. The
      degradation is more pronounced in samples with larger ceramic content due to the
      dissolution of the smaller amount of polymer between the ceramic particles.

PMID- 26301263
TI  - Sports Participation in Genotype Positive Children With Long QT Syndrome.
AB  - OBJECTIVE: The study sought to examine the prevalence and outcomes of sports
      participation (both competitive and recreational) in our single-center LQTS
      genotype positive pediatric population. BACKGROUND: The risks of sports
      participation in patients with long QT syndrome (LQTS) are not clearly
      elucidated. METHODS: A retrospective review was performed on genotype positive
      patients referred for the evaluation and management of LQTS between 1998 and 2013
      at the Children's Hospital of Philadelphia. Pediatric patients participating in
      competitive or recreational sports were included in the analysis and their charts
      were reviewed for documented LQTS events during follow-up. RESULTS: The cohort of
      genotype-positive LQTS patients included 212 patients, and 103 patients (49%,
      female n = 53, average follow-up 7.1 +/- 4.0 years, average QTc 468 +/- 42 ms)
      participated in sports. A total of 105 LQTS disease-causing mutations were
      identified: KCNQ1 n = 60 (58%), KCNH2 n = 36 (35%), SCN5A n = 6 (6%), KCNE1 n = 1
      (1%), and KCNE2 n = 2 (2%). All patients were treated with beta-blockade, with
      noncompliance in 1 patient and intolerance in 1 patient. Twenty-six patients
      participated in competitive sports (26%, female n = 15, average follow-up 6.9 +/-
      4.1 years, average QTc 461 +/- 35 ms). Seventy-seven patients (75%, female n =
      35, average follow-up 7.3 +/- 3.9 years, average QTc 470 +/- 43 ms) participated
      in recreational sports. No patients had LQTS symptoms during sports
      participation. Five appropriate implantable cardioverter-defibrillator shocks
      occurred in 2 patients, though none were related to sports participation.
      CONCLUSIONS: In this series no cardiac events and no deaths were observed in
      treatment-compliant LQTS children while participating in sports in 755 patient
      years of follow-up.

PMID- 26301262
TI  - The role of the autonomic ganglia in atrial fibrillation.
AB  - Recent experimental and clinical studies have shown that the epicardial autonomic
      ganglia play an important role in the initiation and maintenance of atrial
      fibrillation (AF). In this review, we present the current data on the role of the
      autonomic ganglia in the pathogenesis of AF and discuss potential therapeutic
      implications. Experimental studies have demonstrated that acute autonomic
      remodeling may play a crucial role in AF maintenance in the very early stages.
      The benefit of adding ablation of the autonomic ganglia to the standard pulmonary
      vein (PV) isolation procedure for patients with paroxysmal AF is supported by
      both experimental and clinical data. The interruption of axons from these
      hyperactive autonomic ganglia to the PV myocardial sleeves may be an important
      factor in the success of PV isolation procedures. The vagus nerve exerts an
      inhibitory control over the autonomic ganglia and attenuation or loss of this
      control may allow these ganglia to become hyperactive. Autonomic neuromodulation
      using low-level vagus nerve stimulation inhibits the activity of the autonomic
      ganglia and reverses acute electrical atrial remodeling during rapid atrial
      pacing and may provide an alternative non-ablative approach for the treatment of
      AF, especially in the early stages. This notion is supported by a preliminary
      human study. Further studies are warranted to confirm these findings.

PMID- 26301269
TI  - A highly selective fluorescent probe for in vitro and in vivo detection of Hg(2+)
      .
AB  - In this paper, a simple fluorescent probe, rhodamine B derivatives (RS), was
      designed and prepared for sensitive detection of Hg(2+) in CH3CN/H2O (5/5, v/v).
      RS exhibits high selectivity and sensitivity toward Hg(2+) over other common
      metal ions, displaying a significant color change from colorless to pink in the
      presence of Hg(2+). The fluorescence responses remain stable over a broad pH
      range (5.0 to 9.0) and are suitable for detection under physiological conditions.
      Experimental results of HeLa cells and zebrafish show that RS is cell and
      organism permeable. We also demonstrate the acquisition of images of Hg(2+) in
      HeLa cells and zebrafish by using a simple fluorescence confocal imaging
      technique. 

PMID- 26301270
TI  - Key steps towards the oriented immobilization of antibodies using boronic acids.
AB  - Oriented immobilization of antibodies using boronic acids shows a strong
      potential for improving immunoassay performance but is not yet widely used,
      possibly because of the difficulties encountered in its implementation. How to
      choose the boronic acid structure and how should it be attached to the surface?
      How to choose an antibody that will bind to the boronic acid? Under which
      conditions should the binding take place for an effective oriented antibody
      immobilization? How to make sure that the antibody stays on the surface? This
      tutorial review provides answers to these questions through analysis of the
      literature and personal suggestions, and thereby intends to facilitate the
      development of this promising antibody immobilization strategy. 

PMID- 26301271
TI  - An instantly usable paper-based screen-printed solid-state KCl/Ag/AgCl reference
      electrode with long-term stability.
AB  - An instantly usable screen-printed paper-based Ag/AgCl electrode was fabricated
      for use as a cost-effective disposable reference electrode. The reference
      electrode showed potential stability for approximately 75 h. The setup time,
      which is less than 1 min, is much shorter than those for similar previously
      reported electrodes. 

PMID- 26301272
TI  - Scientists Discuss Role of Intellectual Property in Translational Science.

PMID- 26301273
TI  - Regulatory Science Training Vital for Translational Researchers.

PMID- 26301274
TI  - Stage Play Educates Researchers on Responsible Conduct.

PMID- 26301275
TI  - Panelists Discuss Career Opportunities in Translational Science.

PMID- 26301276
TI  - The Hand in Art: Hands on Indian Rupees.

PMID- 26301277
TI  - The Hand in Art: The Hand on the Maltese  2-Euro Coin.

PMID- 26301278
TI  - Retraction notice to "Attachment styles, pain, and the consumption of analgesics
      during labor: A prospective observational study".

PMID- 26301279
TI  - While obviously not the natural environment of biological molecules, the gas
      phase provides the ultimate degree of isolation. Introduction.

PMID- 26301280
TI  - [The role in verbal communication].
AB  - The content of the thought is expressed by words articulated correctly according
      to grammar and syntax. The meanings are conveyed through words but also through
      the way they are used, the manner of communication. The real reason of
      communication is the intention, the purpose, often implicit, which determines the
      source of a speech. It is possible to identify a direct aim (the purpose of
      communicating) and an indirect objective (the role intention), understood as
      keeping a role between the speaker and the listener. The role is also indicated
      by the non-verbal or paraverbal component of the message, that is the tone of
      voice, the emphasis and the posture of the communicator. In the multitude of
      possible relationship (affective, social, business, political, religious),
      frequently bounded together, we can recognize three categories of relations:
      symmetrical, reciprocal and complementary.

PMID- 26301281
TI  - EAPCI Focus on the Working  Group on Interventional  Cardiology of the Latvian 
      Society of Cardiology  An interview with the President,  Andrejs Erglis.

PMID- 26301282
TI  - Are all fish oil supplements safe   during pregnancy?

PMID- 26301283
TI  - A meaningful and sustainable   outreach programme in southern   Gauteng.

PMID- 26301284
TI  - E Cape illegal immune-booster given 'false' approval - officials suspended.

PMID- 26301285
TI  - [Abstracts of the Scientific Communications at the of French Language Neurology
      Days, 2015, Marseille, France].

PMID- 26301286
TI  - SAMA grasps the racial nettle, winning   huge majority vote.

PMID- 26301287
TI  - Netcare - KPMG breached client   privilege to boost Competitions   Commissions
      probe.

PMID- 26301288
TI  - Sexual health in the South African context.

PMID- 26301290
TI  - An integrative treatment model for   patients with sexual dysfunctions.

PMID- 26301289
TI  - Sexual dysfunction: A systematic review   of South African research.
AB  - BACKGROUND: The World Health Organization is in the process of revising the
      International Classification of Diseases and Related Health Problems (ICD).
      Sexual dysfunction disorders (F52) have been identified as having poor clinical
      utility. South Africa (SA) has been selected as one of five low- and middle
      income countries in which studies will be developed to assess the clinical
      utility of the proposed ICD-11 revisions for sexual dysfunction disorders.
      OBJECTIVE: To identify scientific research generated in SA on sexual dysfunction
      disorders to guide these studies. METHODS: A systematic review of SA research on
      sexual dysfunction disorders published in peer-reviewed journals. RESULTS:
      Despite the high prevalence of ejaculatory and erectile dysfunctions, only five
      SA articles have addressed male sexual dysfunction since 1970. Lack of sexual
      interest and inability to reach orgasm are the most commonly reported complaints
      for women, yet only four SA articles have been published on the topic of female
      sexual dysfunction. Diabetes mellitus, cardiovascular disease, genitourinary
      disease and psychiatric or psychological disorders are common comorbid conditions
      associated with sexual dysfunction in both sexes, but only nine articles address
      sexual dysfunction as the main topic with respect to comorbid conditions.
      CONCLUSION: Despite growing awareness of the importance of sexual health, SA
      based scientific research on sexual dysfunction is limited. Further work is
      needed to inform recommendations for ICD-11 revisions drawn from the SA context.

PMID- 26301292
TI  - Male sexual dysfunction.

PMID- 26301291
TI  - Female sexual dysfunction.

PMID- 26301293
TI  - Hypersexual disorder in general practice.

PMID- 26301295
TI  - Sexual function and ageing.

PMID- 26301294
TI  - Transgender issues in South Africa, with particular reference to the Groote
      Schuur Hospital Transgender Unit.

PMID- 26301296
TI  - Abstracts from the 34th Annual Conference of the National Academy of
      Neuropsychology, November 12-15, 2014, Fajardo, Puerto Rico.

PMID- 26301297
TI  - Chronic kidney disease.

PMID- 26301298
TI  - Polymer-Block-Polypeptides and Polymer-Conjugated Hybrid Materials as Stimuli
      Responsive Nanocarriers for Biomedical Applications.
AB  - Stimuli-responsive nanocarriers are a class of soft materials that includes
      natural polymers, synthetic polymers, and polypeptides. Recently, modern
      synthesis tools such as atom transfer radical polymerization, reversible addition
      fragmentation chain transfer polymerization, nitroxide-mediated radical
      polymerization, ring-opening polymerization of alpha-amino acid N
      carboxyanhydrides, and various "click" chemistry strategies were simultaneously
      employed for the design and synthesis of nanosized drug delivery vehicles.
      Importantly, the research focused on the improvement of the nanocarrier
      targetability and the site-specific, triggered release of therapeutics with high
      drug loading efficiency and minimal drug leakage during the delivery to specific
      targets. In this context, nanocarriers responsive to common stimuli such as pH,
      temperature, redox potential, light, etc. have been widely used for the
      controlled delivery of therapeutics to pathological sites. Currently, different
      synthesis and self-assembly strategies improved the drug loading efficacy and
      targeted delivery of therapeutic agents to the desired site. In particular,
      polypeptide-containing hybrid materials have been developed for the controlled
      delivery of therapeutic agents. Therefore, stimuli-sensitive synthetic
      polypeptide-based materials have been extensively investigated in recent years.
      This review focuses on recent advances in the development of polymer-block
      polypeptides and polymer-conjugated hybrid materials that have been designed and
      evaluated for various stimuli-responsive drug and gene delivery applications.

PMID- 26301299
TI  - Nanocomposite Hydrogels and Their Applications in Drug Delivery and Tissue
      Engineering.
AB  - Traditional hydrogels usually possess inferior mechanical properties as well as
      lacking multi-functionalities. Nano-sized particles/fillers, both inorganic and
      organic materials, have unique chemical, physical, and biological functions, and
      have been extensively studied as biomaterials or bio-functional materials.
      Nanocomposite hydrogels, which combine the advantages of both nano-fillers and
      hydrogel matrices, may result in improved mechanical and biological properties
      and find their potential applications in biomedical field. This paper reviews
      recent developments in the synthesis, preparation, and characterization of
      nanocomposite hydrogels; their biomedical applications, such as drug delivery
      matrices and tissue engineering scaffolding materials are also summarized.

PMID- 26301300
TI  - Engineering Virus Capsids Into Biomedical Delivery Vehicles: Structural
      Engineering Problems in Nanoscale.
AB  - Virus capsids have evolved to protect the genome sequestered in their interior
      from harsh environmental conditions, and to deliver it safely and precisely to
      the host cell of choice. This characteristic makes them naturally perfect
      containers for delivering therapeutic molecules to specific locations.
      Development of an ideal virus-based nano-container for medical usage requires
      that the capsid be converted into a targetable protein cage which retains the
      original stability, flexibility and host cell penetrating properties of the
      native particles, without the associated immunogenicity, and is able to
      encapsulate large quantities of therapeutic or diagnostic material. In the last
      few years, several icosahedral, non-enveloped viruses, with a diameter of 25-90
      nm-a size which conveniently falls within the 10-100 nm range desirable for
      biomedical nanoparticles-have been chemically or genetically engineered towards
      partial fulfilment of the above criteria. This review summarizes the approaches
      taken towards engineering viruses into biomedical delivery devices and discusses
      the challenges involved in achieving this goal.

PMID- 26301301
TI  - Preparation and Characterization of RGDS/Nanodiamond as a Vector for VEGF-siRNA
      Delivery.
AB  - Small interfering RNA (siRNA) has great potential for treating or preventing
      diseases. Safe and efficient vectors are extremely needed for specific delivery
      of siRNA. Here VEGF-siRNA/RGDS/nanodiamond was prepared by conjugating Arg-Gly
      Asp-Ser (RGDS) and VEGF-siRNA to nanodiamond delivery particles. VEGF-siRNA could
      be clinically used in anti-angiogenic gene therapy to inhibit tumor growth via
      the down-regulation of the expression of vascular endothelial growth factor
      (VEGF). The differential scanning calorimeter (DSC) analysis evidenced that RGDS
      and/or VEGF-siRNA were effectively linked to nanodiamond. The release assays
      indicated that in the presence of RGDS the release time of VEGF-siRNA was
      prolonged by 6 folds. This enabled VEGF-siRNA/RGDS/nanodiamond to release and
      transfer VEGF-siRNA in a long-acting manner, and thereby to significantly
      decrease the expression of VEGF mRNA and protein. Real-Time PCR analysis revealed
      that the expression of VEGF mRNA was decreased 87.56 +/- 1.6% by VEGF
      siRNA/RGDS/nanodiamond. Enzyme-Linked Immunosorbent Assay (ELISA) indicated that
      the expression of VEGF protein was down-regulated to 39.8 +/- 1.8%. The down
      regulation of VEGF protein expression was also observed in Western blotting
      experiments. In human umbilical vein endothelial cells (HUVEC) test, VEGF
      siRNA/RGDS/nanodiamond decreased the formation of the tubes and exhibited no
      testable cytotoxicty. All the results consistently suggested that
      RGDS/nanodiamond is an ideal non-viral tumor-targeting vector for siRNA transfer,
      and VEGF-siRNA/RGDS/nanodiamond may be a promising regimen of gene therapy in
      carcinoma.

PMID- 26301302
TI  - In Vivo Targeting of Cutaneous Melanoma Using an Melanoma Stimulating Hormone
      Engineered Human Protein Cage with Fluorophore and Magnetic Resonance Imaging
      Tracers.
AB  - Nanoparticle (NP)-based materials are promising agents for enhancing cancer
      diagnosis and treatment. Once functionalized for selective targeting of tumor
      expressed molecules, they can specifically deliver drugs and diagnostic molecules
      inside tumor cells. In the present work, we evaluated the in vivo melanoma
      targeting ability of a nanovector (HFt-MSH-PEG) based on human protein ferritin
      (HFt), functionalized with both melanoma-targeting melanoma stimulating hormone
      (alpha-MSH) and stabilizing poly(ethylene glycol) (PEG) molecules. Independent
      and complementary techniques, such as whole-specimen confocal microscopy and
      magnetic resonance imaging, were used to detect in vivo localization of NP
      constructs with suitable tracers (i.e., fluorophores or magnetic metals).
      Targeted HFt-MSH-PEG NPs accumulated persistently at the level of primary
      melanoma and with high selectivity with respect to other organs. Melanoma
      localization of untargeted HFt-PEG NPs, which lack the alpha-MSH moiety, was less
      pronounced. Furthermore, HFt-MSH-PEG NPs accumulated to a significantly lower
      extent and with a different distribution in a diverse type of tumor (TS/A
      adenocarcinoma), which does not express alpha-MSH receptors. Finally, in a
      spontaneous lung metastasis model, HFt-MSH-PEG NPs localized at the metastasis
      level as well. These results suggest that HFt-MSH-PEG NPs are suitable carriers
      for selective in vivo delivery of diagnostic or therapeutic agents to cutaneous
      melanoma.

PMID- 26301303
TI  - Combination of Anti-Diabetic Drug Metformin and Boswellic Acid Nanoparticles: A
      Novel Strategy for Pancreatic Cancer Therapy.
AB  - Pancreatic cancer has an infaust prognosis and is the fourth common cause of
      cancer related death in India. It is highly resistant to conventional treatment
      modalities such as chemotherapy, radiation therapy and surgery. The association
      of pancreatic cancer and diabetes mellitus is explored in our study. Pancreatic
      cancer is more likely to occur in people who have diabetes than people devoid of
      it, which is supported by the observation that hyperglycaemia occurs at an early
      stage of pancreatic cancer and is indeed a risk factor. In the present study, we
      have demonstrated a synergistic relationship between metformin and boswellic acid
      nanoparticles with varying doses of boswellic acid nanoparticles and constant
      metformin (20 mM). The effect revealed increased synergism between metformin and
      boswellic acid nanoparticles through the inhibition of cell proliferation with an
      effect of 80% for the combination with 0.3 mg/mL and 0.4 mg/mL and a constant
      concentration of metformin. We examined the effect of combination on cell
      migration which revealed time dependent inhibitory effect on pancreatic cell line
      (MiaPaCa-2). Also, we found that the combinatorial approach significantly
      decreased colony formation and exhibited high rate of induction of apoptosis
      through DNA fragmentation in pancreatic cancer cells. In-vitro hemolysis
      confirmed the hemocompatibility of the combination therapy with metformin and
      boswellic acid nanoparticles. Flow cytometry based apoptosis assay and Caspase
      mediated apoptosis proved apoptosis mediated cell death. Further, the cells were
      analysed with mitochondrial membrane potential kit which revealed depolarization
      of mitochondrial membrane potential due to apoptosis after treatment with drug
      combination. Hence, the combination approach proved to be a promising therapy
      towards pancreatic cancer.

PMID- 26301304
TI  - Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) Based Electrospun 3D Scaffolds for
      Delivery of Autogeneic Chondrocytes and Adipose-Derived Stem Cells: Evaluation of
      Cartilage Defects in Rabbit.
AB  - The management of chondral defects has long been a challenge because of the poor
      self-healing capacity of articular cartilage. Many approaches ranging from
      symptomatic treatment to structural cartilage regeneration have obtained very
      limited satisfactory results. Cartilage tissue engineering, which involves an
      optimized combination of novel scaffolds, cell sources and growth factors, has
      emerged as a promising strategy for cartilage regeneration and repair. In this
      study, the cellular morphologies and the adhesion, migration and proliferation
      capabilities of adipose-derived stem cells (ASCs) and chondrocytes seeded on 3D
      scaffolds composed of electrospun poly(3-hydroxybutyrate-co-4-hydroxybutyrate)
      (P3HB4HB) were evaluated. Next, TGF-beta1/scaffolds with 4:1 co-culture of ASCs
      and chondrocytes were implanted into the full thickness cartilage defects in
      rabbit knee for 16 weeks. ASCs and chondrocytes seeded on the scaffolds showed
      better adhesion, migration and proliferation than that on petri dishes in vitro.
      Importantly, implantation with TGF-beta1/scaffolds with delivery of ASCs and
      chondrocytes revealed desirable in vivo healing outcomes. These results
      demonstrate that ASCs have great potential in the field of tissue engineering. It
      is possible that the improvement in ASC-seeded electrospun 3D P3HB4HB scaffolds
      may ultimately lead to improved repair of cartilage injuries.

PMID- 26301306
TI  - Influence of Surface Charge and Polymer Coating on Internalization and
      Biodistribution of Polyethylene Glycol-Modified Iron Oxide Nanoparticles.
AB  - The aim of this study was to investigate the influence of the surface charge and
      coating of Superparamagnetic Iron Oxide Nanoparticles (SPIONs) on their in vitro
      and in vivo behaviors. Neutral and negatively-charged PEG-based SPIONs were
      synthesized and compared to Resovist, a carboxydextran-based SPION currently used
      in clinics. Their cytotoxicity, cell internalization, and potential as contrast
      agents for magnetic resonance imaging were assessed. Neutral pegylated SPIONs
      were internalized less readily by the reticuloendothelial system and showed a
      lower uptake by the liver, compared to negatively-charged SPIONs (with
      carboxydextran and PEG). These results suggested that the charge of
      functionalized SPIONs was more relevant for their biological interactions than
      the nature of their coating.

PMID- 26301305
TI  - Surface Functionalization of Chemically Reduced Graphene Oxide for Targeted
      Photodynamic Therapy.
AB  - In this study, using chemically reduced graphene oxide (GO) as a model
      nanocarbon, we successfully developed a facile surface-functionalization strategy
      of nanocarbons to allow both biocompatibility and receptor targeted drug
      delivery. Polyvinylpyrrolidone (PVP) coating improves aqueous dispersibility and
      biocompatibility of GO, and provides anchoring sites for ACDCRGDCFCG peptide
      (RGD4C). Aromatic photosensitizer chlorin e6 (Ce6) can be effectively loaded into
      the rGO-PVP-RGD system via hydrophobic interactions and pi-pi stacking. The
      nanodelivery system can significantly increase the accumulation of Ce6 in tumor
      cells and lead to an improved photodynamic therapy (PDT) efficacy as compared to
      Ce6 alone. The facile surface functionalization strategy can be applied to other
      nanomaterials such as carbon nanotubes, and inorganic nanomaterials.

PMID- 26301307
TI  - Graphitized-Carbon-Nanofiber Paper-Enzyme Electrode Fabrication Through Non
      Covalent Modification for Enzyme Biofuel Cell Application.
AB  - Carbon nanofibers are an emerging smart material that are promising for use as a
      biosensor and a biofuel cell transducer material due to their morphological and
      electrochemical characteristics. In particular, graphitized carbon nanofibers
      possess unique structures of graphite-like edges within their high surface area
      that provide a large active site for enzyme attachment. For a specific
      application such as a biofuel cell, which requires highly stable electrical
      communication and electricity generation, non-covalent enzyme immobilization
      using bifunctional molecule is suggested as an appropriate approach because it
      does not change the carbon hybridization from sp2 to sp3 as covalent
      immobilization by acid treatment does. Graphitized carbon-nanofiber paper (GCNFp)
      electrode were fabricated through dispersion-filtration method in which glucose
      oxidase as model enzyme were immobilized by a bifunctional molecule that forms pi
      pi stacking of the pyrene moiety with the nanofiber wall coupled by a reactive
      end-amine reaction. This system provides a practical enzyme-electrode hybrid that
      facilitates comparatively faster enzyme-electrode electrical communication than
      other system using similar material, as calculated from the heterogeneous
      electron-transfer rate constant (K(s)) which was 5.45 s(-1).

PMID- 26301308
TI  - Functionalized Polyacrylonitrile Nanofibrous Membranes for Covalent
      Immobilization of Glucose Oxidase.
AB  - Nanofibrous membrane (NFM) with uniform morphology and large surface area was
      prepared from 10% solution of polyacrylonitrile (PAN) in N,N-dimethylformamide by
      electrospinning technique. NFM was chemically modified for use as a support for
      the immobilization of glucose oxidase. Chemical modification of NFM was carried
      out by two different methods. In the first method, the cyano groups of PAN were
      modified to amino groups by a two-step process, while in the second method the
      carboxylic groups were generated first and then further reacted with
      hexamethylene diamine to create a reactive spacer arm for the immobilization of
      enzyme. Scanning electron microscopy studies showed that the surface morphology
      of NFM was not changed by chemical modification and its mechanical strength was
      improved. The immobilized glucose oxidase (GOx) retained 54 and 60% of its
      original activity up to 25 cycles with the PAN NFMs modified by the first and the
      second method, respectively. The GOx-immobilized NFM from the second method
      showed promising performance with higher enzyme immobilization, activity
      retention, and favorable kinetic parameters.

PMID- 26301309
TI  - Engineered Carbon Nanotube Buckypaper: A Platform for Electrochemical Biosensors.
AB  - Much recent research has focused on electrochemical biosensors to meet the
      growing demands for rapid and accurate diagnostic tests for diseases, detecting
      toxic molecules present in the environment, and biomolecules used as in
      pharmaceuticals. Carbon nanotubes (CNTs) have been shown to be effective for
      electrochemical biosensors because of their favorable chemical, physical and
      electrical properties. Here we report the use of a two-dimensional entangled mat
      of CNTs, known as buckypaper, as electrodes for electrochemical biosensors. The
      buckypaper electrodes exhibit superior sensitivity towards tryptophan, L
      carnitine, tyrosine and myoglobin. When engineered with metals or other specific
      molecules, the buckypaper shows an up to 1000-fold increase in the signal
      compared with electrodes based on glassy carbon. This enhanced electrochemical
      performance of the modified buckypaper demonstrates potential for a new platform
      for electrochemical biosensor technologies.

PMID- 26301310
TI  - Adhesion of Poly(phenylene sulfide) Resin with Polymeric Film of Triazine Thiol
      on Aluminum Surface Modified by Anodic Oxidation.
AB  - Various surface modifications have been applied to improve the adhesion
      properties of aluminum for the cap plate and sealing quality of electrolyte on Li
      ion batteries. In this study, we have tried to find the effective condition for
      the polymerization of triazine thiols (TT) on modified aluminum surfaces by
      anodic aluminum oxide. Characterization of polymerized films on aluminum was
      explored by scanning electron microscopy, X-ray photoelectron spectroscopy, and
      secondary ion mass spectroscopy analysis. Scanning electron microscopy results
      reveal that meaningful roughness was formed on aluminum surfaces by anodic
      oxidation. Secondary ion mass spectroscopy analysis results represent that the
      peel strength was found to depend on film thickness and the composition of the
      adhesion layer. As a result, Al/PPS (polyphenylene sulfide) resin assemblies
      developed in this study have superior adhesive property. Therefore, these
      assemblies might be a viable candidate for a sealing technique for Li ion
      batteries.

PMID- 26301311
TI  - Simultaneous Effect of Thiolation and Carboxylation of Chitosan Particles Towards
      Mucoadhesive Oral Insulin Delivery Applications: An In Vitro and In Vivo
      Evaluation.
AB  - Thiomalyl chitosan (TCS), a pH sensitive thiolated chitosan derivative, was
      developed and investigated towards oral protein delivery application. Particles
      of z-average 364 +/- 5.6 nm with a negative zeta potential of 14.4 mV was
      obtained by tripolyphosphate cross linking of TCS. The release of insulin from
      TCS particles was significantly restricted at pH 1.2 minimizing up to about < 10%
      in 3 hours. The permeation enhancement ratio was found to 13 times higher than
      the FD4 alone and was 1.6 times higher than the unmodified chitosan particles.
      The protein protective properties of the matrix were established in presence of
      pepsin and pancreatic enzymes. Confocal microscopy studies proved the tight
      junction opening of Caco-2 cells by these thiolated chitosan particles and the in
      vivo studies on diabetic rats established its potential towards oral peptide
      delivery with pharmacological availability (PA) of 1.5%. The significance of this
      work is to establish that, the presence of multiple functional groups having
      similar property in the same matrix can improve its suitability as a promising
      candidate for oral peptide delivery with improved release characteristics,
      mucoadhesion as well as protecting the insulin activity and enhancing the
      permeability across the intestinal wall.

PMID- 26301312
TI  - Efficacy and Hemotoxicity of Stealth Doxorubicin-Loaded Magnetic Nanovectors on
      Breast Cancer Xenografts.
AB  - In the field of oncology, research is now focused on the development of
      theranostic nanosystems that combine the functions of drug delivery and imaging
      for diagnosis/monitoring. In this context, we designed polyethylene glycol
      (PEG)ylated superparamagnetic iron oxide nanoparticles (SPIONs) for the delivery
      of doxorubicin (DOX), an antineoplastic agent. These DOX-loaded PEGylated SPIONs,
      or DLPS, should be useful for the delivery of DOX in vivo, as well as for
      magnetic drug targeting (MDT) and magnetic resonance imaging (MRI). The aim of
      this study was to evaluate the potential applications of DLPS in vivo as drug
      carrier systems for the reduction of xenograft breast tumors induced in nude
      mice. Prior to the animal model experiments, the main internalization pathways
      for the nanovectors in MDA-MB435 breast cancer cells were determined to be based
      on caveolae- and clathrin-mediated endocytosis. The time- and quantity-dependence
      of the nanoparticle uptake by the cells altered the in vitro cytotoxicity of the
      DLPS. The in vitro antiproliferative effect of the DLPS was dependent not only on
      DOX concentration, but also on the efficacy of nanoparticle internalization.
      Evaluation of the effect of DLPS treatment on xenograft tumors in nude mice
      showed that DLPS limited tumor growth in a manner comparable to that of free DOX
      under normal conditions of tumor growth. The application of an external magnetic
      field on tumors, i.e., MDT, did not improve the efficacy of the DLPS treatment.
      Nevertheless, the vectorization of DOX with DLPS appears to limit the hematologic
      side effects usually associated with DOX treatment.

PMID- 26301314
TI  - The TRIB3-SQSTM1 interaction mediates metabolic stress-promoted tumorigenesis and
      progression via suppressing autophagic and proteasomal degradation.
AB  - Cancer and diabetes are 2 multifactorial chronic diseases with tremendous impact
      on health worldwide. Metabolic risk factors play a critical role in fueling a
      wide range of cancers, but with undefined mechanisms. We recently reported that
      TRIB3, a stress-induced protein, mediates a reciprocal antagonism between
      autophagic and proteasomal degradation systems and connects insulin-IGF1 to
      malignant promotion. We found that several human cancer tissues express higher
      TRIB3 and phosphorylated IRS1 (insulin receptor substrate 1), which correlates
      negatively with patient prognosis. Silencing of TRIB3 not only restores insulin
      IGF1-suppressed autophagic flux, but also attenuates tumor growth and metastasis.
      TRIB3 physically interacts with the autophagic receptor SQSTM1, and this
      interaction hinders the binding of SQSTM1 to LC3 and ubiquitinated proteins,
      leading to SQSTM1 accumulation and clearance inhibition of ubiquitinated
      proteins. Interrupting the TRIB3-SQSTM1 interaction with an alpha-helical peptide
      derived from SQSTM1 attenuates tumor growth and metastasis through activating
      autophagic flux. Our findings indicate that TRIB3 links insulin-IGF1 to cancer
      development and progression through interacting with SQSTM1. Thus, interrupting
      the TRIB3-SQSTM1 interaction may provide a potential strategy against cancers in
      patients with diabetes. 

PMID- 26301313
TI  - Maintenance of species boundaries in a Neotropical radiation of Begonia.
AB  - A major goal of evolutionary biology is to determine the mechanisms generating
      biodiversity. In Begonia, one of the largest plant genera (1900+ species), it has
      been postulated that the high number of endemic species is a by-product of low
      gene flow among populations, which predisposes the group to speciation. However,
      this model of divergence requires that reproductive barriers accumulate rapidly
      among diverging species that overlap in their geographic ranges, otherwise
      speciation will be opposed by homogenizing gene flow in zones of secondary
      contact. Here, we test the outcomes of secondary contact in Begonia by genotyping
      multiple sympatric sites with 12 nuclear and seven plastid loci. We show that
      three sites of secondary contact between B. heracleifolia and B. nelumbiifolia
      are highly structured, mostly containing parental genotypes, with few F1 hybrids.
      A sympatric site between B. heracleifolia and B. sericoneura contains a higher
      proportion of F1s, but little evidence of introgression. The lack of later
      generation hybrids contrasts with that documented in many other plant taxa, where
      introgression is extensive. Our results, in conjunction with previous genetic
      work, show that Begonia demonstrate properties making them exceptionally prone to
      speciation, at multiple stages along the divergence continuum. Not only are
      populations weakly connected by gene flow, promoting allopatric speciation, but
      species often show strong reproductive barriers in secondary contact. Whether
      similar mechanisms contribute to diversification in other large genera remains to
      be tested. 

PMID- 26301315
TI  - Immune Responses to Virulent and Vaccine Strains of Infectious Bronchitis Viruses
      in Chickens.
AB  - Infectious bronchitis (IB) is an acute and highly contagious chicken viral
      disease, causing severe economic losses to poultry producers worldwide. In the
      last few decades, infectious bronchitis virus (IBV) has been extensively studied,
      but knowledge of immune responses to virulent or vaccine strains of IBVs remains
      limited. This review focuses on fundamental aspects of immune responses against
      IBV, including the role of pattern recognition receptors (PRRs) in identification
      of conserved viral structures and the role of different components of innate
      immunity (e.g., heterophils, macrophages, dendritic cells, acute phase protein,
      and cytokines). Studies on adaptive immune activation and the role of humoral and
      cellular immunity in IBV clearance are also reviewed. Multiple interlinking
      immune responses are essential for protection against virulent IBVs, including
      passive, innate, adaptive, and effector T cells active at mucosal surfaces.
      Although the development of approaches for chicken transcriptome and proteome
      analyses have greatly helped the understanding of the underlying genetic
      mechanisms for immunity, there are still major knowledge gaps, such as the role
      of mucosal and cellular responses to IBVs. In view of recent reports of emergent
      IBV variants in many countries, there is renewed interest in a more complete
      understanding of poultry immune responses to both virulent and vaccine strains of
      IBVs. This will be critical for developing new vaccine or vaccination strategies
      and other intervention programs. 

PMID- 26301316
TI  - Ensuring a Diverse Physician Workforce: Progress but More to Be Done.

PMID- 26301317
TI  - The anisotropic mechanical behaviour of electro-spun biodegradable polymer
      scaffolds: Experimental characterisation and constitutive formulation.
AB  - Electro-spun biodegradable polymer fibrous structures exhibit anisotropic
      mechanical properties dependent on the degree of fibre alignment. Degradation and
      mechanical anisotropy need to be captured in a constitutive formulation when
      computational modelling is used in the development and design optimisation of
      such scaffolds. Biodegradable polyester-urethane scaffolds were electro-spun and
      underwent uniaxial tensile testing in and transverse to the direction of
      predominant fibre alignment before and after in vitro degradation of up to 28
      days. A microstructurally-based transversely isotropic hyperelastic continuum
      constitutive formulation was developed and its parameters were identified from
      the experimental stress-strain data of the scaffolds at various stages of
      degradation. During scaffold degradation, maximum stress and strain in
      circumferential direction decreased from 1.02 +/- 0.23 MPa to 0.38 +/- 0.004 MPa
      and from 46 +/- 11 % to 12 +/- 2 %, respectively. In longitudinal direction,
      maximum stress and strain decreased from 0.071 +/- 0.016 MPa to 0.010 +/- 0.007
      MPa and from 69 +/- 24 % to 8 +/- 2 %, respectively. The constitutive parameters
      were identified for both directions of the non-degraded and degraded scaffold for
      strain range varying between 0% and 16% with coefficients of determination
      r(2)>0.871. The six-parameter constitutive formulation proved versatile enough to
      capture the varying non-linear transversely isotropic behaviour of the fibrous
      scaffold throughout various stages of degradation.

PMID- 26301318
TI  - The biomaterials challenge: A comparison of polyethylene wear using a hip joint
      simulator.
AB  - Although hip arthroplasty is an established procedure that relieves pain and
      improves functions, problems remain with wear and osteolysis. Highly cross-linked
      polyethylene and Vitamin-E-stabilized polyethylene were introduced in the last
      years to solve these problems. In this study we compared the in vitro wear
      behaviour of cross-linked polyethylene (XLPE) versus Vitamin-E diffused XLPE
      (XLPE_VE) versus conventional ultra-high molecular weight polyethylene (UHMWPE)
      acetabular cups. The test was performed using a hip joint simulator run for two
      millions cycles under bovine calf serum as lubricant. Mass loss was found to
      decrease along the series UHMWPE>XLPE_VE>XLPE, although statistically significant
      differences were found only between the mass losses of XLPE and UHMWPE at 1.2 and
      2 million cycles. The mass loss data were explained in relation to the
      crystalline morphology of the control unworn cups, as investigated by non
      destructive micro-Raman spectroscopy. This technique allowed to disclose a
      different wear behaviour of the three sets of cups. Wear testing produced a
      stress-induced crystallisation in UHMWPE, with increases in both amorphous
      (alphaa) and orthorhombic (alphao) phases at the expense of the third phase
      (alphab), which decreased upon wear. Moreover, the all-trans content decreased,
      while the ortho-trans content increased, contrarily to the trend observed for
      XLPE and XLPE_VE, for which no statistically significant changes in alphao,
      alphaa and alphab contents were detected. The XLPE_VE specimens underwent the
      least significant changes in the spectroscopic markers of micromorphology upon
      mechanical stress, probably due to their lower starting amorphous content. 

PMID- 26301319
TI  - Lightweight, Superelastic, and Mechanically Flexible Graphene/Polyimide
      Nanocomposite Foam for Strain Sensor Application.
AB  - The creation of superelastic, flexible three-dimensional (3D) graphene-based
      architectures is still a great challenge due to structure collapse or significant
      plastic deformation. Herein, we report a facile approach of transforming the
      mechanically fragile reduced graphene oxide (rGO) aerogel into superflexible 3D
      architectures by introducing water-soluble polyimide (PI). The rGO/PI
      nanocomposites are fabricated using strategies of freeze casting and thermal
      annealing. The resulting monoliths exhibit low density, excellent flexibility,
      superelasticity with high recovery rate, and extraordinary reversible
      compressibility. The synergistic effect between rGO and PI endows the elastomer
      with desirable electrical conductivity, remarkable compression sensitivity, and
      excellent durable stability. The rGO/PI nanocomposites show potential
      applications in multifunctional strain sensors under the deformations of
      compression, bending, stretching, and torsion. 

PMID- 26301320
TI  - M3Ag17(SPh)12 Nanoparticles and Their Structure Prediction.
AB  - Although silver nanoparticles are of great fundamental and practical interest,
      only one structure has been determined thus far: M4Ag44(SPh)30, where M is a
      monocation, and SPh is an aromatic thiolate ligand. This is in part due to the
      fact that no other molecular silver nanoparticles have been synthesized with
      aromatic thiolate ligands. Here we report the synthesis of M3Ag17(4-tert
      butylbenzene-thiol)12, which has good stability and an unusual optical spectrum.
      We also present a rational strategy for predicting the structure of this
      molecule. First-principles calculations support the structural model, predict a
      HOMO-LUMO energy gap of 1.77 eV, and predict a new "monomer mount" capping motif,
      Ag(SR)3, for Ag nanoparticles. The calculated optical absorption spectrum is in
      good correspondence with the measured spectrum. Heteroatom substitution was also
      used as a structural probe. First-principles calculations based on the structural
      model predicted a strong preference for a single Au atom substitution in
      agreement with experiment.

PMID- 26301321
TI  - Leiomyoma of the third eyelid in a dog.
AB  - A 14-year-old neutered male Dachshund presented for the evaluation of oculus
      dexter (OD) third eyelid elevation ongoing for approximately 2 months. Complete
      ophthalmic examination revealed a large, nonpainful, well-demarcated, soft mass
      at the base of the right third eyelid causing elevation and mild hyperemia. The
      mass was freely moveable with the third eyelid, and no right globe deviation was
      noted. No other abnormalities were noted on physical examination, routine blood
      chemistry, complete blood count, serum T4, urinalysis, or urine
      cortisol/creatinine ratio. Ocular B-mode ultrasonography showed an anechoic, well
      demarcated, homogenous, soft tissue mass at the base of the third eyelid with no
      orbital extension. A leiomyoma was diagnosed after multiple punch biopsies were
      obtained from the palpebral surface of the mass. The right third eyelid was
      excised surgically. Histopathology confirmed a completely excised, nodular,
      unencapsulated, expansile mass within the third eyelid. Positive smooth muscle
      actin and negative S-100 immunohistochemistry confirmed a leiomyoma. Bundles of
      normal smooth muscle were also present adjacent to the mass. The mass was
      compressing the adjacent lacrimal gland and associated with moderate
      dacryoadenitis. Twelve months postoperatively, the right globe position and
      motility remain normal with no evidence of mass regrowth. To the author's
      knowledge, this is the first reported case of a leiomyoma of the third eyelid in
      any species. In this case, the mass was completely excised and no regrowth has
      occurred twelve months after surgery. This case along with independently reviewed
      canine third eyelids clearly demonstrates the presence of smooth muscle within
      the canine third eyelid.

PMID- 26301322
TI  - Prevalence of shoulder pain in Swedish flatwater kayakers and its relation to
      range of motion and scapula stability of the shoulder joint.
AB  - Few studies have investigated the incidence of injuries in kayakers. The aim was
      to study the prevalence of shoulder pain in competitive flatwater kayakers and to
      evaluate any differences in range of motion or scapula stability of the shoulder
      joint among kayakers with or without the history of shoulder pain. Thirty-one
      kayakers were participated in the study, and a questionnaire including background
      data was used. Shoulder range of motion was measured with a goniometer, and the
      participants were observed for scapula dyskinesis in flexion and abduction. Of
      the participating kayakers, 54.8% (n = 17) had experienced shoulder pain.
      Kayakers who had experienced shoulder pain showed a significantly lower degree of
      internal rotational range of motion versus kayakers with no reported shoulder
      pain, with a mean degree of internal rotation in the right shoulder 49.3 vs. 60.0
      (P = 0.017) and the left shoulder 51.9 vs. 66.0 (P = 0.000). Kayakers who had
      experienced shoulder pain were also observed with a scapular dyskinesis (n = 15
      of 17 kayakers) to a significantly higher degree (P = 0.001) than kayakers with
      no reported shoulder pain. Findings suggest that screening for scapular
      dyskinesis and testing for rotational range of motion in the shoulder joint is
      essential in order to treat and maybe prevent shoulder pain in kayakers.

PMID- 26301323
TI  - Cost-Effectiveness of Adding Cardiac Resynchronization Therapy to an Implantable
      Cardioverter-Defibrillator Among Patients With Mild Heart Failure.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) reduces mortality and heart
      failure hospitalizations in patients with mild heart failure. OBJECTIVE: To
      estimate the cost-effectiveness of adding CRT to an implantable cardioverter
      defibrillator (CRT-D) compared with implantable cardioverter-defibrillator (ICD)
      alone among patients with left ventricular systolic dysfunction, prolonged
      intraventricular conduction, and mild heart failure. DESIGN: Markov decision
      model. DATA SOURCES: Clinical trials, clinical registries, claims data from
      Centers for Medicare & Medicaid Services, and Centers for Disease Control and
      Prevention life tables. TARGET POPULATION: Patients aged 65 years or older with a
      left ventricular ejection fraction (LVEF) of 30% or less, QRS duration of 120
      milliseconds or more, and New York Heart Association (NYHA) class I or II
      symptoms. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: CRT-D or
      ICD alone. OUTCOME MEASURES: Life-years, quality-adjusted life-years (QALYs),
      costs, and incremental cost-effectiveness ratios (ICERs). RESULTS OF BASE-CASE
      ANALYSIS: Use of CRT-D increased life expectancy (9.8 years versus 8.8 years),
      QALYs (8.6 years versus 7.6 years), and costs ($286 500 versus $228 600),
      yielding a cost per QALY gained of $61 700. RESULTS OF SENSITIVITY ANALYSES: The
      cost-effectiveness of CRT-D was most dependent on the degree of mortality
      reduction: When the risk ratio for death was 0.95, the ICER increased to $119 600
      per QALY. More expensive CRT-D devices, shorter CRT-D battery life, and older age
      also made the cost-effectiveness of CRT-D less favorable. LIMITATIONS: The
      estimated mortality reduction for CRT-D was largely based on a single trial. Data
      on patients with NYHA class I symptoms were limited. The cost-effectiveness of
      CRT-D in patients with NYHA class I symptoms remains uncertain. CONCLUSION: In
      patients with an LVEF of 30% or less, QRS duration of 120 milliseconds or more,
      and NYHA class II symptoms, CRT-D appears to be economically attractive relative
      to ICD alone when a reduction in mortality is expected. PRIMARY FUNDING SOURCE:
      National Institutes of Health, University of Copenhagen, U.S. Department of
      Veterans Affairs.

PMID- 26301324
TI  - Development and comparison of the methods for quantitative electron probe X-ray
      microanalysis analysis of thin specimens and their application to biological
      material.
AB  - In recent years, there has been a return to the use of electron probe X-ray
      microanalysis for biological studies but this has occurred at a time when the
      Hall programme which acted as the mainstay for biological microanalysis is no
      longer easily available. Commercial quantitative routines rely on the Cliff
      Lorimer method that was originally developed for materials science applications.
      Here, the development of these two main routines for obtaining quantitative data
      from thin specimens is outlined and the limitations that are likely to be met
      when the Cliff-Lorimer routine is applied to biological specimens is discussed.
      The effects of specimen preparation on element content is briefly summarized and
      the problems encountered when using quantitative analysis on resin-embedded
      materials emphasized. 

PMID- 26301325
TI  - Neuronal pattern separation in the olfactory bulb improves odor discrimination
      learning.
AB  - Neuronal pattern separation is thought to enable the brain to disambiguate
      sensory stimuli with overlapping features, thereby extracting valuable
      information. In the olfactory system, it remains unknown whether pattern
      separation acts as a driving force for sensory discrimination and the learning
      thereof. We found that overlapping odor-evoked input patterns to the mouse
      olfactory bulb (OB) were dynamically reformatted in the network on the timescale
      of a single breath, giving rise to separated patterns of activity in an ensemble
      of output neurons, mitral/tufted (M/T) cells. Notably, the extent of pattern
      separation in M/T assemblies predicted behavioral discrimination performance
      during the learning phase. Furthermore, exciting or inhibiting GABAergic OB
      interneurons, using optogenetics or pharmacogenetics, altered pattern separation
      and thereby odor discrimination learning in a bidirectional way. In conclusion,
      we propose that the OB network can act as a pattern separator facilitating
      olfactory stimulus distinction, a process that is sculpted by synaptic
      inhibition. 

PMID- 26301326
TI  - Coordinated forms of noradrenergic plasticity in the locus coeruleus and primary
      auditory cortex.
AB  - The cerebral cortex is plastic and represents the world according to the
      significance of sensory stimuli. However, cortical networks are embodied in
      complex circuits, including neuromodulatory systems such as the noradrenergic
      locus coeruleus, providing information about internal state and behavioral
      relevance. Although norepinephrine is important for cortical plasticity, it is
      unknown how modulatory neurons themselves respond to changes of sensory input. We
      examined how locus coeruleus neurons are modified by experience and the
      consequences of locus coeruleus plasticity for cortical representations and
      sensory perception. We made whole-cell recordings from rat locus coeruleus and
      primary auditory cortex (A1), pairing sounds with locus coeruleus activation.
      Although initially unresponsive, locus coeruleus neurons developed and maintained
      auditory responses afterwards. Locus coeruleus plasticity induced changes in A1
      responses lasting at least hours and improved auditory perception for days to
      weeks. Our results demonstrate that locus coeruleus is highly plastic, leading to
      substantial changes in regulation of brain state by norepinephrine. 

PMID- 26301328
TI  - Highly Transparent and Flexible Triboelectric Nanogenerators with Subwavelength
      Architectured Polydimethylsiloxane by a Nanoporous Anodic Aluminum Oxide
      Template.
AB  - Highly transparent and flexible triboelectric nanogenerators (TENGs) were
      fabricated using the subwavelength-architectured (SWA) polydimethylsiloxane
      (PDMS) with a nanoporous anodic aluminum oxide (AAO) template as a replica mold.
      The SWA PDMS could be utilized as a multifunctional film for a triboelectric
      layer, an antireflection coating, and a self-cleaning surface. The nanopore
      arrays of AAO were formed by a simple, fast, and cost-effective electrochemical
      oxidation process of aluminum, which is relatively impressive for fabrication of
      the TENG device. For electrical contacts, the SWA PDMS was laminated on the
      indium tin oxide (ITO)-coated polyethylene terephthalate (PET) as a bottom
      electrode, and the bare ITO-coated PET (i.e., ITO/PET) was used for the top
      electrode. Compared to the ITO/PET, the SWA PDMS on the ITO/PET improved the
      transmittance from 80.5 to 83% in the visible wavelength region and also had high
      transmittances of >85% at wavelengths of 430-455 nm. The SWA PDMS also exhibited
      the hydrophobic surface with a water contact angle (thetaCA) of ~115 degrees ,
      which can be useful for self-cleaning applications. The average transmittance
      (Tavg) of the entire TENG device was observed to be ~70% over a broad wavelength
      range. At an external pushing frequency of 0.5 Hz, for the TENG device with the
      ITO top electrode, open-circuit voltage (VOC) and short-circuit current (ISC)
      values of ~3.8 V and ~0.8 MUA were obtained instantaneously, respectively, which
      were higher than those (i.e., VOC ~ 2.2 V, and ISC ~ 0.4 MUA) of the TENG device
      with a gold top electrode. The effect of external pushing force and frequency on
      the output device performance of the TENGs was investigated, including the device
      robustness. A theoretical optical analysis of SWA PDMS was also performed. 

PMID- 26301329
TI  - Impact of intestinal ultrasound on classification and management of Crohn disease
      patients with inconclusive colonoscopy.

PMID- 26301327
TI  - BET protein Brd4 activates transcription in neurons and BET inhibitor Jq1 blocks
      memory in mice.
AB  - Precise regulation of transcription is crucial for the cellular mechanisms
      underlying memory formation. However, the link between neuronal stimulation and
      the proteins that directly interact with histone modifications to activate
      transcription in neurons remains unclear. Brd4 is a member of the bromodomain and
      extra-terminal domain (BET) protein family, which binds acetylated histones and
      is a critical regulator of transcription in many cell types, including
      transcription in response to external cues. Small molecule BET inhibitors are in
      clinical trials, yet almost nothing is known about Brd4 function in the brain.
      Here we show that Brd4 mediates the transcriptional regulation underlying
      learning and memory. The loss of Brd4 function affects critical synaptic
      proteins, which results in memory deficits in mice but also decreases seizure
      susceptibility. Thus Brd4 provides a critical link between neuronal activation
      and the transcriptional responses that occur during memory formation. 

PMID- 26301331
TI  - Colonic stents for colorectal cancer are seldom used and mainly for palliation of
      obstruction: A population-based study.

PMID- 26301330
TI  - Polyethylene glycol versus sodium picosulfalte bowel preparation in the setting
      of a colorectal cancer screening program.
AB  - BACKGROUND: Adequate bowel preparation for colonoscopy is an important predictor
      of colonoscopy quality. OBJECTIVE: To determine the difference in terms of
      effectiveness between different existing colon cleansing products in the setting
      of a colorectal cancer screening program. METHODS: The records of consecutive
      patients who underwent colonoscopy at the Montreal General Hospital (Montreal,
      Quebec) between April 2013 and April 2014 were retrospectively extracted from a
      dedicated electronic digestive endoscopic institutional database. RESULTS:
      Overall, 2867 charts of patients undergoing colonoscopy were assessed, of which
      1130 colonoscopies were performed in a screening setting; patients had adequate
      bowel preparation in 90%. Quality of preparation was documented in only 61%.
      Bowel preparation was worse in patients receiving sodium picosulfate (PICO) alone
      compared with polyethylene glycol, in a screening setting (OR 0.3 [95% CI 0.2 to
      0.6]). Regardless of the preparation type, the odds of achieving adequate quality
      cleansing was 6.6 for patients receiving a split-dose regimen (OR 6.6 [95% CI 2.1
      to 21.1]). In multivariable analyses, clinical variables associated with
      inadequate bowel preparation in combined population were use of PICO, a nonsplit
      regimen and inpatient status. The polyp detection rate was very high (45.6%) and
      was correlated with withdrawal time. CONCLUSION: Preparation quality needs to be
      more consistently included in the colonoscopy report. Split-dose regimens
      increased the quality of colon cleansing across all types of preparations and
      should be the preferred method of administration. Polyethylene glycol alone
      provided better bowel cleansing efficacy than PICO in a screening setting but
      PICO remains an alternative in association with an adjuvant.

PMID- 26301332
TI  - A 14-day course of triple therapy is superior to a 10-day course for the
      eradication of Helicobacter pylori: A Canadian study conducted in a 'real world'
      setting.
AB  - BACKGROUND: Successful Helicobacter pylori eradication with the traditional seven
      day course of proton pump inhibitor (PPI) triple therapy is declining. Prolonging
      therapy to either 10 or 14 days is associated with better eradications rates.
      OBJECTIVE: To compare the effectiveness of 14-day course of triple therapy versus
      a 10-day course in the treatment of H pylori in Canada. METHODS: Consecutive
      treatment-naive patients with clinical indications for H pylori eradication
      underwent either a 10-day course or a 14-day course of traditional PPI triple
      therapy depending on the date of the office visit (an odd date received the 10
      day course, whereas an even date received the 14-day treatment). H pylori
      eradication was ascertained via urea breath test or gastric biopsies performed
      >=4 weeks after completion of therapy. Analyses were by both intention to treat
      and per-protocol. RESULTS: A total of 83 patients were included in the study (31
      in the 10-day group and 52 in the 14-day group). In the intention-to-treat
      analysis, eradication rates were 82.7% (95% CI 70% to 92%) versus 45.2% (95% CI
      27% to 64%), favouring the 14-day treatment (P<0.001). Similarly, in the per
      protocol analysis, eradication rates were 91.5% (95% CI 80% to 98%) versus 63.6%
      (95% CI 41% to 83%), favouring the 14-day arm (P=0.01). Adverse events and
      compliance were not significantly different between the two groups. CONCLUSION: A
      14-day course of standard PPI triple therapy was superior to a shorter-duration
      therapy and should be included as a first-line regimen for H pylori eradication
      in Canada. The 10-day course of treatment did not achieve an acceptable
      eradication rate and should no longer be used in this country.

PMID- 26301334
TI  - Seed-Mediated Growth of Anatase TiO2 Nanocrystals with Core-Antenna Structures
      for Enhanced Photocatalytic Activity.
AB  - We demonstrate that anatase TiO2 nanocrystals composed of a nanocrystal core and
      nanorod antennas can be produced via a nonaqueous colloidal seed-mediated growth
      method. Anatase TiO2 nanocrystals with defined morphologies were first prepared
      as seeds, and then secondary anatase TiO2 nanorods were grown on the defined
      facets of the seeds under appropriate conditions. Systematic studies on the
      growth mechanism reveal that the formation of core-antenna nanocrystals involves
      an epitaxial growth process with specific orientational preference governed by
      both thermodynamic and kinetic factors. By manipulating the reaction conditions
      including the precursor amount and introduction rate, the epitaxial growth
      behavior can be well controlled. By further varying the morphology of seed
      nanocrystals, we have also been able to produce core-antenna anatase TiO2
      nanocrystals with complex spatial configurations in a highly predictable manner.
      The high structural configurability and predictability offered by this seed
      mediated growth method may provide great opportunities in enhancing the
      performance of TiO2-based nanostructures in many energy-related applications. As
      a demonstration, we show by simply manipulating the core-antenna structures that
      the photocatalytic activity of the anatase nanocrystals can be improved from the
      relatively less active seed nanocrystals or pure nanorods to the extent that
      exceeds the activity of the commercial P25 titania. 

PMID- 26301333
TI  - Interferon-based hepatitis C antiviral treatment outcomes may be predicted by
      alanine aminotransferase levels.

PMID- 26301335
TI  - Development of a bench-top device for parallel climate-controlled recordings of
      neuronal cultures activity with microelectrode arrays.
AB  - Two binding requirements for in vitro studies on long-term neuronal networks
      dynamics are (i) finely controlled environmental conditions to keep neuronal
      cultures viable and provide reliable data for more than a few hours and (ii)
      parallel operation on multiple neuronal cultures to shorten experimental time
      scales and enhance data reproducibility. In order to fulfill these needs with a
      Microelectrode Arrays (MEA)-based system, we designed a stand-alone device that
      permits to uninterruptedly monitor neuronal cultures activity over long periods,
      overcoming drawbacks of existing MEA platforms. We integrated in a single device:
      (i) a closed chamber housing four MEAs equipped with access for chemical
      manipulations, (ii) environmental control systems and embedded sensors to
      reproduce and remotely monitor the standard in vitro culture environment on the
      lab bench (i.e. in terms of temperature, air CO2 and relative humidity), and
      (iii) a modular MEA interface analog front-end for reliable and parallel
      recordings. The system has been proven to assure environmental conditions stable,
      physiological and homogeneos across different cultures. Prolonged recordings (up
      to 10 days) of spontaneous and pharmacologically stimulated neuronal culture
      activity have not shown signs of rundown thanks to the environmental stability
      and have not required to withdraw the cells from the chamber for culture medium
      manipulations. This system represents an effective MEA-based solution to
      elucidate neuronal network phenomena with slow dynamics, such as long-term
      plasticity, effects of chronic pharmacological stimulations or late-onset
      pathological mechanisms.

PMID- 26301336
TI  - Baicalein attenuates hypertrophic scar formation via inhibition of the
      transforming growth factor-beta/Smad2/3 signalling pathway.
AB  - BACKGROUND: Hypertrophic scars (HPSs) are characterized by excessive fibrosis
      associated with aberrant function of fibroblasts. Currently no satisfactory
      treatment has been developed. OBJECTIVES: To investigate the effect of baicalein
      on HPSs and its underlying mechanisms. METHODS: Baicalein was administered
      intradermally (10 MUmol L(-1) in 100 MUL sterile saline plus 10%
      dimethylsulfoxide) to mechanical-load-induced scars in mice once a day for 14 or
      28 days. Histological and immunohistochemical studies were performed to evaluate
      scar hypertrophy and the function of fibroblasts. Human HPS-derived fibroblasts
      (HSFs) were determined by immunofluorescence study, collagen gel contraction
      assay and wound-healing assay. Also, protein expression of the transforming
      growth factor (TGF)-beta signalling pathway was detected using Western blotting.
      Lastly, a molecular docking study and kinase binding assay were conducted in
      search of the potential interaction between baicalein and activin receptor-like
      kinase (ALK)5. RESULTS: Baicalein treatment significantly attenuated HPS
      formation and collagen deposition in a mechanical-load-induced mouse model.
      Baicalein also inhibited the proliferation and activation of fibroblasts in vitro
      and in vivo. Furthermore, baicalein impaired the contractile and migration
      ability of HSFs. Protein expression investigation revealed that baicalein had an
      inhibitory effect on TGF-beta/Smad2/3 signalling. Such bioactivity of baicalein
      may result from its selective binding to the ATP-binding pocket of ALK5, as
      suggested by the molecular docking study and kinase binding assay. CONCLUSIONS:
      Baicalein could serve as a promising agent for treatment of HPSs and a selective
      ALK5 inhibitor.

PMID- 26301338
TI  - Injectable Bone Substitute Based on beta-TCP Combined With a Hyaluronan
      Containing Hydrogel Contributes to Regeneration of a Critical Bone Size Defect
      Towards Restitutio ad Integrum.
AB  - In the present in vivo study, the regenerative potential of a new injectable bone
      substitute (IBS) composed of beta-tricalcium phosphate (beta-TCP) and hyaluronan
      was tested in a rabbit distal femoral condyle model. To achieve this, 2 defects
      of 6 mm in diameter and 10 mm in length were drilled into each femur condyle in a
      total of 12 animals. For each animal, 1 hole was filled with the substitute
      material, and the other was left empty to serve as the control. After 1, 3, and 6
      months, the regenerative process was analyzed by radiography as well as by
      histological and histomorphometrical analysis. The results revealed that bone
      tissue formation took place through osteoconductive processes over time, starting
      from the defect borders to the center. Both the beta-TCP content and the hydrogel
      support bone tissue growth. The histomorphometrical measurements showed that the
      amount of bone formation in the experimental group was significantly higher
      compared with that found in the control group after 3 months (19.51 +/- 5.08% vs.
      1.96 +/- 0.77%, P < .05) and 6 months (4.57 +/- 1.56% vs. 0.23 +/- 0.21%, P <
      .05). The application of the IBS gave a restitutio ad integrum result after 6
      months and was associated with its nearly complete degradation, in contrast to
      the results found in the control group. In conclusion, the results of the present
      study demonstrate that the IBS contributes to sufficient bone regeneration by
      serving as a scaffold-like structure, combined with its degradation within 6
      months. 

PMID- 26301337
TI  - Task-based evaluation of a 4D MAP-RBI-EM image reconstruction method for gated
      myocardial perfusion SPECT using a human observer study.
AB  - We evaluated the performance of a new 4D image reconstruction method for improved
      4D gated myocardial perfusion (MP) SPECT using a task-based human observer study.
      We used a realistic 4D NURBS-based Cardiac-Torso (NCAT) phantom that models
      cardiac beating motion. Half of the population was normal; the other half had a
      regional hypokinetic wall motion abnormality. Noise-free and noisy projection
      data with 16 gates/cardiac cycle were generated using an analytical projector
      that included the effects of attenuation, collimator-detector response, and
      scatter (ADS), and were reconstructed using the 3D FBP without and 3D OS-EM with
      ADS corrections followed by different cut-off frequencies of a 4D linear post
      filter. A 4D iterative maximum a posteriori rescaled-block (MAP-RBI)-EM image
      reconstruction method with ADS corrections was also used to reconstruct the
      projection data using various values of the weighting factor for its prior. The
      trade-offs between bias and noise were represented by the normalized mean squared
      error (NMSE) and averaged normalized standard deviation (NSDav), respectively.
      They were used to select reasonable ranges of the reconstructed images for use in
      a human observer study. The observers were trained with the simulated cine images
      and were instructed to rate their confidence on the absence or presence of a
      motion defect on a continuous scale. We then applied receiver operating
      characteristic (ROC) analysis and used the area under the ROC curve (AUC) index.
      The results showed that significant differences in detection performance among
      the different NMSE-NSDav combinations were found and the optimal trade-off from
      optimized reconstruction parameters corresponded to a maximum AUC value. The 4D
      MAP-RBI-EM with ADS correction, which had the best trade-off among the tested
      reconstruction methods, also had the highest AUC value, resulting in
      significantly better human observer detection performance when detecting regional
      myocardial wall motion abnormality. We concluded that the NMSE-NSDav trade-off
      was shown to agree with observer performance for the detection task of the
      regional motion abnormality, and the optimized 4D MAP-RBI-EM method with ADS
      corrections provides significant improvement compared to 3D FBP and 3D OS-EM with
      ADS corrections in detecting regional myocardial wall motion abnormali in 4D
      gated MP SPECT. 

PMID- 26301340
TI  - A comparison of spontaneous problem-solving abilities in three estrildid finch
      (Taeniopygia guttata, Lonchura striata var. domestica, Stagonopleura guttata)
      species.
AB  - Cognition has been extensively studied in primates while other, more distantly
      related taxa have been neglected for a long time. More recently, there has been
      an increased interest in avian cognition, with the focus mostly on big-brained
      species like parrots and corvids. However, the majority of bird species has never
      systematically been studied in diverse cognitive tasks other than memory and
      learning tasks, so not much can yet be concluded about the relevant factors for
      the evolution of cognition. Here we examined 3 species of the estrildid finch
      family in problem-solving tasks. These granivorous, non-tool-using birds are
      distributed across 3 continents and are not known for high levels of innovation
      or spontaneous problem solving in the wild. In this study, our aim was to find
      such abilities in these species, assess what role domestication might play with a
      comparison of 4 genetically separated zebra finch strains, and to look for
      between-species differences between zebra finches, Bengalese finches, and diamond
      firetails. Furthermore, we established a 3-step spontaneous problem-solving
      procedure with increasing levels of complexity. Results showed that some
      estrildid finches were generally capable of spontaneously solving problems of
      variable complexity to obtain food. We found striking differences in these
      abilities between species, but not between strains within species, and offer a
      discussion of potential reasons. Our established methodology can now be applied
      to a larger number of bird species for phylogenetic comparisons on the behavioral
      level to get a deeper understanding of the evolution of cognitive abilities.

PMID- 26301339
TI  - Terahertz-Triggered Phase Transition and Hysteresis Narrowing in a Nanoantenna
      Patterned Vanadium Dioxide Film.
AB  - We demonstrate that high-field terahertz (THz) pulses trigger transient insulator
      to-metal transition in a nanoantenna patterned vanadium dioxide thin film. THz
      transmission of vanadium dioxide instantaneously decreases in the presence of
      strong THz fields. The transient THz absorption indicates that strong THz fields
      induce electronic insulator-to-metal transition without causing a structural
      transformation. The transient phase transition is activated on the subcycle time
      scale during which the THz pulse drives the electron distribution of vanadium
      dioxide far from equilibrium and disturb the electron correlation. The strong THz
      fields lower the activation energy in the insulating phase. The THz-triggered
      insulator-to-metal transition gives rise to hysteresis loop narrowing, while
      lowering the transition temperature both for heating and cooling sequences. THz
      nanoantennas enhance the field-induced phase transition by intensifying the field
      strength and improve the detection sensitivity via antenna resonance. The
      experimental results demonstrate a potential that plasmonic nanostructures
      incorporating vanadium dioxide can be the basis for ultrafast, energy-efficient
      electronic and photonic devices. 

PMID- 26301341
TI  - Structural Features of Micelles of Zwitterionic Dodecyl-phosphocholine (C12PC)
      Surfactants Studied by Small-Angle Neutron Scattering.
AB  - Small-angle neutron scattering (SANS) was used to investigate the size and shape
      of zwitterionic dodecyl phosphocholine (C12PC) micelles formed at various
      concentrations above its critical micelle concentration (CMC = 0.91 mM). The
      predominant spherical shape of micelles is revealed by SANS while the average
      micellar size was found to be broadly consistent with the hydrodynamic diameters
      determined by dynamic light scattering (DLS). Cryogenic tunneling electron
      microscopy (cryo-TEM) shows a uniform distribution of structures, proposing
      micelle monodispersity ( Supporting Information ). H/D substitution was utilized
      to selectively label the chain, head, or entire surfactant so that structural
      distributions within the micellar assembly could be investigated using fully
      protonated, head-deuterated, and tail-deuterated PC surfactants in D2O and fully
      deuterated surfactants in H2O. Using the analysis software we have developed, the
      four C12PC contrasts at a given concentration were simultaneously analyzed using
      various core-shell models consisting of a hydrophobic core and a shell
      representing hydrated polar headgroups. Results show that at 10 mM, C12PC
      micelles can be well represented by a spherical core-shell model with a core
      radius and shell thicknesses of 16.9 +/- 0.5 and 10.2 +/- 2.0 A (total radius
      27.1 +/- 2.0 A), respectively, with a surfactant aggregation number of 57 +/- 5.
      As the concentration was increased, the SANS data revealed an increase in core
      shell mixing, characterized by the emergence of an intermediate mixing region at
      the spherical core-shell interface. C12PC micelles at 100 mM were found to have a
      core radius and shell thicknesses of 19.6 +/- 0.5 and 7.8 +/- 2.0 A, with an
      intermediate mixing region of 3.0 +/- 0.5 A. Further reduction in the shell
      thickness with concentration was also observed, coupled with an increased mixing
      of the core and shell regions and a reduction in miceller hydration, suggesting
      that concentration has a significant influence on surfactant packing and
      aggregation within micelles. 

PMID- 26301343
TI  - Do we always need anticoagulation before cardioversion of atrial fibrillation in
      ladies?

PMID- 26301344
TI  - Ischemia-modified albumin levels in patients with acute decompensated heart
      failure treated with dobutamine or levosimendan: IMA-HF study.
AB  - OBJECTIVE: Ischemia-modified albumin (IMA) is a sensitive biomarker of myocardial
      ischemia. However, data on IMA levels in acute heart failure (HF) are still
      lacking. In this study, we aimed to evaluate serum IMA levels in acute
      decompensated HF and the effects of dobutamine and levosimendan treatments on IMA
      levels. METHODS: This was a prospective, multicenter study that included 70
      patients hospitalized with acute decompensated HF and left ventricular ejection
      fraction < 35%. Blood samples for IMA measurements were obtained on admission and
      24-48 h after the initiation of HF therapy. Twenty-nine patients were treated
      with standard HF therapy, 18 received levosimendan, and 23 received dobutamine in
      addition to standard of care. A single serum specimen was also collected from 32
      healthy individuals each. IMA concentrations were measured by the albumin cobalt
      binding colorimetric assay, and the results were given in absorbance units (AU).
      Independent and paired sample t-tests, Mann-Whitney U test, and Wilcoxon signed
      rank test were used for the analysis. RESULTS: In patients with acute
      decompensated HF, the serum concentration of IMA was significantly higher than
      those of healthy subjects (0.894 +/- 0.23 AU vs. 0.379 +/- 0.08 AU, p < 0.001).
      Overall, the IMA levels significantly decreased after 24-48 h of HF therapy
      (0.894 +/- 0.23 AU and 0.832 +/- 0.18 AU, p = 0.013). Furthermore, the IMA levels
      were also found to significantly decrease with standard HF therapy (1.041 +/-
      0.28 vs. 0.884 +/- 0.15 AU, p = 0.041), with levosimendan (0.771 +/- 0.18 vs.
      0.728 +/- 0.18 AU, p = 0.046) and also with dobutamine (0.892 +/- 0.18 vs. 0.820
      +/- 0.13 AU, p = 0.035). CONCLUSION: Patients with acute decompensated HF had
      elevated IMA levels, and appropriate HF therapy significantly reduced the serum
      IMA levels. Dobutamine or levosimendan did not increase the IMA levels,
      suggesting a lower potential in inducing myocardial ischemia when used in
      recommended doses.

PMID- 26301345
TI  - Role of ischemia-modified albumin in patients with acute decompensated heart
      failure.

PMID- 26301346
TI  - Which oracle to use for tracking a desynchronized heart? A matter of
      predictability in contemporary medicine.

PMID- 26301348
TI  - Assessment of left ventricular functions with tissue Doppler, strain, and strain
      rate echocardiography in patients with familial Mediterranean fever.

PMID- 26301347
TI  - Comparison of endothelial function of coronary artery bypass grafts in diabetic
      and nondiabetic patients: Which graft offers the best?
AB  - OBJECTIVE: Diabetes associated endothelial dysfunction, which determines both
      long and short term graft patency, is not uniform in all coronary artery bypass
      surgery (CABG) grafts. Herein this study, we aimed to investigate the degree of
      endothelial dysfunction in diabetic radial artery (RA), internal mammarian artery
      (IMA) and saphenous vein (SV) grafts in vitro tissue bath system. METHODS: This
      is a prospective experimental study. Fifteen diabetic and 15 non-diabetic
      patients were included to the study. A total number of 96 graft samples were
      collected; 16 graft samples for each graft type from both diabetic and non
      diabetic patients. Arterial grafts were harvested with pedicles and SV grafts
      were harvested by 'no touch' technique. Vasodilatation response of vascular rings
      to carbachol, which induces nitric oxide (NO) mediated vasodilatation, was
      designated as the measure of endothelial function. RESULTS: The IMA grafts had
      the most prominent NO mediated vasodilatation in both diabetic and non-diabetic
      patients, concluding a better preserved endothelial function than SV and RA. The
      'no- touch' SV and RA grafts had similar vasodilatation responses in non-diabetic
      patients. In diabetic patients, on the other hand, RA grafts exhibited the least
      vasodilatation response (ie. worst endothelial function), even less
      vasodilatation than 'no touch' SV grafts (p<0.0001). CONCLUSION: Deteriorated
      function of RA grafts in diabetic patients, even worse than SV grafts made
      evident by this study, encourages the use of 'no touch' technique as the method
      of SV harvesting and more meticulous imaging of RA before its use as a graft in
      diabetic patients.

PMID- 26301349
TI  - Dissolution of an apical thrombus by apixaban in a patient with old anteroseptal
      myocardial infarction.

PMID- 26301350
TI  - A rare association with suffered cardiac arrest, long QT interval, and
      syndactyly: Timothy syndrome (LQT-8).

PMID- 26301351
TI  - Low atrial rhythm mimics myocardial infarction.

PMID- 26301352
TI  - OSACS score--a new simple tool for identifying high risk for obstructive sleep
      apnea syndrome based on clinical parameters.

PMID- 26301353
TI  - Effect of percutaneous mitral balloon valvuloplasty on right ventricular
      functions in mitral stenosis: Short-and mid-term results.

PMID- 26301354
TI  - Platelet to lymphocyte ratio: a novel and simple predictor of slow coronary flow.

PMID- 26301355
TI  - How can we reduce complications associated with thrombolysis for prosthetic valve
      thrombosis?

PMID- 26301356
TI  - Transcatheter aortic valve implantation for severe pure aortic regurgitation:
      looking beyond the image.

PMID- 26301357
TI  - Ebola virus disease 2014: Induction of abnormal cardiac rhythm?

PMID- 26301358
TI  - Interview with Prof. Dr. Murat Tuzcu.

PMID- 26301359
TI  - Kosuyolu and "30 Years of Pride Story". This light will always be on.

PMID- 26301361
TI  - Echocardiographic imaging of saccular aneurysm in the left main coronary artery.

PMID- 26301362
TI  - Three-dimensional imaging of left ventricular hemangioma.

PMID- 26301363
TI  - Anisotropic field-of-view support for golden angle radial imaging.
AB  - PURPOSE: To provide anisotropic field-of-view (FOV) support for golden angle
      radial imaging. THEORY AND METHODS: In radial imaging, uniform spoke density
      leads to a circular FOV, which is excessive for objects with anisotropic
      dimensions. Larson et al previously showed that the angular k-space spoke density
      can be determined by the desired anisotropic FOV. We show that conventional
      golden angle sampling can be deployed in an angle-normalized space and
      transformed back to k-space such that the desired nonuniform spoke density is
      preserved for arbitrary temporal window length. Elliptical FOVs were used to
      illustrate this generalized mapping approach. Point-spread-function and spoke
      density analysis was performed. Phantom and in vivo cardiac images were acquired.
      RESULTS: Simulations, phantom, and in vivo experiments confirmed that the
      proposed method is able to achieve anisotropic FOV while still maintaining the
      benefits of golden angle sampling. This approach requires 50% less spokes for
      elliptical FOV with major-to-minor-axis ratio of 1:0.3, when compared with
      isotropic FOV with the same undersampling factor. CONCLUSION: We demonstrate a
      simple method for applying golden angle view ordering to anisotropic FOV radial
      imaging. This can reduce imaging time for objects with anisotropic dimensions
      while still allowing arbitrary temporal window selection. Magn Reson Med 76:229
      236, 2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 26301364
TI  - Clozapine and anemia: a 2-year follow-up study.
AB  - OBJECTIVE: Clozapine's association with agranulocytosis led to the implementation
      of stringent and mandatory hematologic monitoring guidelines in most countries.
      Although other hematologic aberrations such as eosinophilia and neutropenia have
      been previously described, clozapine's impact on the erythroid lineage has not
      been studied. There is a suspicion that a higher rate of anemia is observed in
      patients receiving clozapine; therefore, we hypothesized that there would be a
      higher rate of anemia in patients receiving clozapine therapy. METHOD: All
      individuals initiated on clozapine at our center from 2009 to 2010 were
      recruited. Information on age, gender, medical comorbidities, and smoking status
      was extracted from the medical records. Data from complete blood counts over a 2
      year follow-up period were extracted, with anemia defined as a hemoglobin value
      below 120 g/L for women and 130 g/L for men. Time to anemia event was calculated
      and Cox regression was employed to identify predictors of anemia. RESULTS: We
      found a high incidence of anemia in the first 2 years following clozapine
      initiation; of the 94 individuals (68 men, 26 women) recruited, 23 (24.5%)
      developed anemia. Higher baseline hemoglobin level (hazard ratio [HR] = 0.86, P =
      .002) and smoking status (HR = 0.21, P = .021) were identified as significant
      protective factors against anemia in men but not in women (HR = 0.92, P = .184,
      and HR = 0.52, P = .467 for baseline hemoglobin and smoking, respectively).
      CONCLUSIONS: Although smoking appears to lower the risk of anemia, we believe
      this is due to smoking's up-regulation of hemoglobin levels. Further studies are
      warranted in light of the present findings; for example, we cannot exclude the
      possibility that anemia was an epiphenomenon, characterizing instead a population
      with severe mental illness.

PMID- 26301366
TI  - Dry Eye Disease.

PMID- 26301370
TI  - Evidence of neurodegeneration in obstructive sleep apnea: Relationship between
      obstructive sleep apnea and cognitive dysfunction in the elderly.
AB  - The incidence of dementia and obstructive sleep apnea (OSA) increases with age.
      Late-onset Alzheimer's disease (AD) is an irreversible neurodegenerative disease
      of the elderly characterized by amyloid beta (Abeta) plaques and neurofibrillary
      tangles. The disease involves widespread synaptic loss in the neocortex and the
      hippocampus. Rodent and clinical studies suggest that OSA impairs the structural
      integrity of several brain regions, including the medial temporal lobe. Indeed,
      hypoxia, hypertension, hypoperfusion, endothelial dysfunction, inflammation, and
      oxidative stress noted in OSA patients also occur in AD patients. This Review
      highlights pathological commonality, showing that OSA upregulates Abeta, tau
      hyperphosphorylation, and synaptic dysfunction. Indeed, OSA and hypertension
      trigger hypoperfusion and hypometabolism of brain regions, including cortex and
      hippocampus. Several studies show that hypertension-driven brain damage and
      pathogenic mechanisms lead to an Abeta increase. The pathophysiological mechanism
      by which OSA enhances hypertension may be linked to sympathoexcitation, oxidative
      stress, and endothelial dysfunction. Strong pathophysiological similarities that
      exist between OSA and AD are underscored here. For example, the hippocampus is
      negatively impacted in both OSA and AD. OSA promotes hippocampal atrophy, which
      is associated with memory impairment. Cognitive impairment, even in the absence
      of manifest dementia, is an important independent predictor of mortality.
      However, several pathophysiological mechanisms in OSA are reversible with
      appropriate therapy. OSA, therefore, is a modifiable risk factor of cognitive
      dysfunction, and treating OSA prior to mild cognitive impairment may be an
      effective prevention strategy to reduce risk for cognitive decline and AD in
      middle-aged persons and the elderly.

PMID- 26301371
TI  - Estimating Oceanic Primary Production Using Vertical Irradiance and Chlorophyll
      Profiles from Ocean Gliders in the North Atlantic.
AB  - An autonomous underwater vehicle (Seaglider) has been used to estimate marine
      primary production (PP) using a combination of irradiance and fluorescence
      vertical profiles. This method provides estimates for depth-resolved and
      temporally evolving PP on fine spatial scales in the absence of ship-based
      calibrations. We describe techniques to correct for known issues associated with
      long autonomous deployments such as sensor calibration drift and fluorescence
      quenching. Comparisons were made between the Seaglider, stable isotope ((13)C),
      and satellite estimates of PP. The Seaglider-based PP estimates were comparable
      to both satellite estimates and stable isotope measurements.

PMID- 26301372
TI  - Fludarabine in the Treatment of Refractory Chronic Inflammatory Demyelinating
      Neuropathies.
AB  - Inflammatory demyelinating neuropathies have variable responses to
      immunomodulating therapy. Eight patients with chronic inflammatory neuropathies
      who were refractory to standard therapy were treated with fludarabine, a
      combination of fludarabine and cyclophosphamide, and in 1 case with fludarabine
      and rituximab. Five patients with immunoglobulin M anti-myelin-associated
      glycoprotein neuropathies received fludarabine. Three patients with chronic
      inflammatory demyelinating polyneuropathy received a combination of fludarabine
      and cyclophosphamide. All 8 patients improved in either functional status or
      strength with minimal toxicities. Most patients experienced sustained remission
      after the use of fludarabine or fludarabine and cyclophosphamide. Fludarabine
      alone or in combination with cyclophosphamide should be considered for patients
      with inflammatory demyelinating neuropathies, refractory to other treatments. 

PMID- 26301373
TI  - Primary Neurolymphomatosis Presenting With Polyradiculoneuropathy Affecting One
      Lower Limb.
AB  - OBJECTIVES: We report a case of primary neurolymphomatosis (NL) with unusual
      presentation and excellent treatment response. METHODS: Chart review. RESULTS: A
      64-year-old woman presented with 2 months of progressive pain, weakness, and
      numbness in her right leg. Nerve conduction study/electromyogram suggested a
      right lumbosacral radiculoplexus neuropathy with associated acute right peroneal
      neuropathy at the fibular head. L/S spine and right leg magnetic resonance
      imaging showed thickening and contrast enhancement of the right S1 nerve root and
      the right distal sciatic, tibial, and common peroneal nerves, as well as a
      lobular enhancing lesion of the right superficial peroneal nerve. Whole-body
      fludeoxyglucose-positron emission tomography scan showed no other lesions. A
      right superficial peroneal nerve lesion biopsy revealed infiltration of the nerve
      by diffuse large B-cell lymphoma. The lymphoma cells expressed BCL2 but not CD10,
      suggesting an origin in peripheral blood not lymph nodes. Despite the expression
      of BCL2, which is considered as a poor prognosis marker, our patient responded
      very well to the combined radiotherapy and chemotherapy with the R-MPV
      (rituximab, MTX, procarbazine, and vincristine) regimen. The patient showed
      marked clinical improvement and complete resolution of lymphoma lesions on the
      PET scan. CONCLUSIONS: Our case broadens the clinical spectrum and illustrates
      the importance of early diagnosis and aggressive treatment of primary NL.

PMID- 26301374
TI  - Atypical Presentation for Friedreich Ataxia in a Child.
AB  - The classic phenotype of Friedreich ataxia is characterized by dysarthria,
      progressive limb and trunk ataxia, loss of reflexes, and gait disturbance with
      the onset of disease before the second decade. Homozygous trinucleotide repeat
      expansion of GAA in the FXN gene is found in 98% of patients. Two-5% of all
      patients have a repeat expansion on one allele and a point mutation on the other
      allele. Atypical phenotype is found in 25% of patients. A 10-year-old boy
      presented with congenital biliary atresia and progressive gait abnormality. His
      examination was significant for spastic gait, hyperreflexia, and sensory
      neuropathy. Genetic testing revealed a compound heterozygous mutation in the FXN
      gene. The absence of dysarthria and ataxia, retention of reflexes, absence of
      diabetes, and variable development of cardiomyopathy support a slow progression
      of disease with compound heterozygous mutation at G130V. Missense mutations are
      rare causes of Friedreich ataxia that can only be detected by sequencing of the
      FXN gene. Sequencing of the FXN gene is essential to make an early diagnosis when
      there is an atypical phenotype. 

PMID- 26301375
TI  - Recurrent Isolated Sixth Nerve Palsy in Relapsing-Remitting Chronic Inflammatory
      Demyelinating Polyneuropathy.
AB  - INTRODUCTION: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an
      immune-mediated sensory and motor demyelinating polyneuropathy that typically
      presents as a relapsing-remitting or progressive disorder. Cranial neuropathies
      infrequently occur in association with other more typical symptoms of CIDP. CASE
      REPORT: We report a case of CIDP with recurrent isolated sixth nerve palsy. Her
      physical examination showed a right sixth nerve palsy and absent deep tendon
      reflexes as the only indicator of her disease. Magnetic resonance imaging
      revealed thickening without enhancement of the trigeminal and sixth cranial
      nerves. Nerve conduction study (NCS) revealed a sensory and motor demyelinating
      polyneuropathy with conduction block and temporal dispersion in multiple nerves
      consistent with CIDP. Cerebrospinal fluid demonstrated albuminic-cytologic
      dissociation. She had a remarkable response to intravenous immunoglobulin and
      remains asymptomatic without any additional immunomodulating therapy.
      CONCLUSIONS: Isolated cranial neuropathies can rarely occur as the sole
      manifestation of relapsing-remitting CIDP. The profound demyelination found on
      NCS in this case demonstrates that there can be a dramatic discordance between
      the clinical and electrodiagnostic findings in some patients with this disorder.

PMID- 26301376
TI  - Correlation of Changes in Gait Parameters, With Phenotype, Outcome Measures, and
      Electrodiagnostic Abnormalities in a Patient With Anti-MAG Neuropathy After
      Exacerbation and Improvement.
AB  - Gait impairment is a common presentation in patients with IgM anti-myelin
      associated glycoprotein (anti-MAG) antibody demyelinating neuropathy. However,
      current methods used to assess gait are limited. We report spatiotemporal gait
      parameters captured by GAITRite, a computerized walkway with embedded pressure
      sensors. The patient worsened after treatment with rituximab and subsequently
      improved with intravenous immunoglobulin. Serial gait assessments were performed
      at baseline and after treatment. Spatiotemporal gait parameters correlated with
      Medical Research Council sum score, Inflammatory Neuropathy Cause and Treatment
      disability score, and grip strength. Quantitative gait assessment may provide a
      new dimension to standard clinical evaluation and may help to clarify treatment
      response in patients with anti-MAG neuropathy when used in combination with other
      validated assessment tools. 

PMID- 26301377
TI  - False-Positive Serum Botulism Bioassay in Miller-Fisher Syndrome.
AB  - We describe a patient with acute progressive weakness and areflexia. Both
      botulism and Miller-Fisher variant of Guillain-Barre syndrome were initial
      diagnostic considerations, and she was treated with intravenous immunoglobulin
      and botulinum antitoxin. A mouse bioassay was positive for botulinum toxin A,
      although her clinical course, electrodiagnostic studies, and cerebrospinal fluid
      findings supported Miller-Fisher syndrome. This patient's atypical features offer
      points of discussion regarding the evaluation of patients with acute
      neuromuscular weakness and emphasize the limitations of the botulism bioassay. 

PMID- 26301379
TI  - Split Hand Associated With Monomelic Amyotrophy: A Challenging Diagnosis.

PMID- 26301378
TI  - Neuromuscular Pathology Case.

PMID- 26301381
TI  - Genetic resources offer efficient tools for rice functional genomics research.
AB  - Rice is an important crop and major model plant for monocot functional genomics
      studies. With the establishment of various genetic resources for rice genomics,
      the next challenge is to systematically assign functions to predicted genes in
      the rice genome. Compared with the robustness of genome sequencing and
      bioinformatics techniques, progress in understanding the function of rice genes
      has lagged, hampering the utilization of rice genes for cereal crop improvement.
      The use of transfer DNA (T-DNA) insertional mutagenesis offers the advantage of
      uniform distribution throughout the rice genome, but preferentially in gene-rich
      regions, resulting in direct gene knockout or activation of genes within 20-30 kb
      up- and downstream of the T-DNA insertion site and high gene tagging efficiency.
      Here, we summarize the recent progress in functional genomics using the T-DNA
      tagged rice mutant population. We also discuss important features of T-DNA
      activation- and knockout-tagging and promoter-trapping of the rice genome in
      relation to mutant and candidate gene characterizations and how to more
      efficiently utilize rice mutant populations and datasets for high-throughput
      functional genomics and phenomics studies by forward and reverse genetics
      approaches. These studies may facilitate the translation of rice functional
      genomics research to improvements of rice and other cereal crops. 

PMID- 26301382
TI  - Two-Dimensional Electronic Spectroscopy of Light-Harvesting Complex II at Ambient
      Temperature: A Joint Experimental and Theoretical Study.
AB  - We have performed broad-band two-dimensional (2D) electronic spectroscopy of
      light-harvesting complex II (LHCII) at ambient temperature. We found that
      electronic dephasing occurs within ~60 fs and inhomogeneous broadening is
      approximately 120 cm(-1). A three-dimensional global fit analysis allows us to
      identify several time scales in the dynamics of the 2D spectra ranging from 100
      fs to ~10 ps and to uncover the energy-transfer pathways in LHCII. In particular,
      the energy transfer between the chlorophyll b and chlorophyll a pools occurs
      within ~1.1 ps. Retrieved 2D decay-associated spectra also uncover the spectral
      positions of corresponding diagonal peaks in the 2D spectra. Residuals in the
      decay traces exhibit periodic modulations with different oscillation periods.
      However, only one of them can be associated with the excitonic cross-peaks in the
      2D spectrum, while the remaining ones are presumably of vibrational origin. For
      the interpretation of the spectroscopic data, we have applied a refined exciton
      model for LHCII. It reproduces the linear absorption, circular dichroism, and 2D
      spectra at different waiting times. Several components of the energy transport
      are revealed from theoretical simulations that agree well with the experimental
      observations. 

PMID- 26301383
TI  - Effects of preservatives on Alicyclobacillus acidoterrestris growth and guaiacol
      production.
AB  - Alicyclobacillus acidoterrestris can survive the pasteurization process, multiply
      in pasteurized juices and produce guaiacol which causes medicinal or antiseptic
      off-flavors. Chemical preservatives have the potential to suppress outgrowth of
      surviving populations during subsequent storage of fruit juices. In the present
      study, the individual effects of potassium sorbate, sodium benzoate, potassium
      metabisulfite, dehydroacetic acid, ethyl 4-hydroxybenzoate, cinnamic acid and
      epsilon-polylysine on A. acidoterrestris growth and guaiacol production were
      firstly evaluated in a laboratory medium. Of the seven preservatives
      investigated, only dehydroacetic acid, cinnamic acid and epsilon-polylysine were
      effective both in controlling growth and guaiacol formation by A.
      acidoterrestris. Then, these three antimicrobials were applied to apple juice.
      Through the addition of 270 mg/L dehydroacetic acid, 108 mg/L cinnamic acid or
      100 mg/L epsilon-polylysine, the A. acidoterrestris counts were reduced by 3.43,
      3.17 and 4.78 log colony forming unit(CFU)/mL, respectively, and no guaiacol was
      detected after 14 days of storage. Sensory evaluation revealed that the addition
      of these three preservatives did not affect the organoleptic properties of the
      apple juice. Results obtained in this paper could be very useful for a better
      control of A. acidoterrestris-related spoilage in the fruit juice/beverage
      industry.

PMID- 26301384
TI  - Association Between Physical Therapy and Risk of Coronary Artery Disease and
      Dyslipidemia Among Osteoarthritis Patients: A Nationwide Database Study.
AB  - OBJECTIVE: To provide empirical evidence on the effect of early physical therapy
      (PT) within the first year of osteoarthritis (OA) diagnosis on reduction in OA
      related comorbidities in patients with OA. DESIGN: Retrospective cohort study.
      SETTING: The study was conducted using a nationally representative sample of 1
      million National Health Insurance enrollees. PARTICIPANTS: Newly diagnosed
      patients with OA (N=13,545). One-to-one propensity score matching was used to
      match patients who received PT within the first year of OA diagnosis (PT group;
      n=3403) with an equal number of patients with OA who did not receive PT (non-PT
      group). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The 4-year
      cumulative risk of comorbidities including coronary artery disease (CAD),
      diabetes mellitus, dyslipidemia, osteoporosis, gastrointestinal tract ulcer, and
      renal failure was estimated. A Cox proportional hazards regression analysis was
      performed to identify the dose-response relation between the PT dosage and the
      risk of OA-related comorbidities. RESULTS: A total of 3403 patients (25.1%)
      received PT within the first year of OA diagnosis. The PT group had a
      significantly lower 4-year cumulative risk of dyslipidemia (P=.05) and a
      potentially lower 4-year cumulative risk of CAD (P=.09). After adjusting for
      other potential confounders, the Cox proportional hazards regression analysis
      showed that patients with OA who received a high PT dosage had a low risk of CAD
      and dyslipidemia. CONCLUSIONS: Patients with OA who received PT had a lower risk
      of OA-related comorbidities such as dyslipidemia or CAD.

PMID- 26301385
TI  - Dextrose Prolotherapy Versus Control Injections in Painful Rotator Cuff
      Tendinopathy.
AB  - OBJECTIVE: To compare the effect of dextrose prolotherapy on pain levels and
      degenerative changes in painful rotator cuff tendinopathy against 2 potentially
      active control injection procedures. DESIGN: Randomized controlled trial, blinded
      to participants and evaluators. SETTING: Outpatient pain medicine practice.
      PARTICIPANTS: Persons (N=73) with chronic shoulder pain, examination findings of
      rotator cuff tendinopathy, and ultrasound-confirmed supraspinatus
      tendinosis/tear. INTERVENTIONS: Three monthly injections either (1) onto painful
      entheses with dextrose (Enthesis-Dextrose), (2) onto entheses with saline
      (Enthesis-Saline), or (3) above entheses with saline (Superficial-Saline). All
      solutions included 0.1% lidocaine. All participants received concurrent
      programmed physical therapy. MAIN OUTCOME MEASURES: Primary: participants
      achieving an improvement in maximal current shoulder pain >=2.8 (twice the
      minimal clinically important difference for visual analog scale pain) or not.
      Secondary: improvement in the Ultrasound Shoulder Pathology Rating Scale (USPRS)
      and a 0-to-10 satisfaction score (10, completely satisfied). RESULTS: The 73
      participants had moderate to severe shoulder pain (7.0+/-2.0) for 7.6+/-9.6
      years. There were no baseline differences between groups. Blinding was effective.
      At 9-month follow-up, 59% of Enthesis-Dextrose participants maintained >=2.8
      improvement in pain compared with Enthesis-Saline (37%; P=.088) and Superficial
      Saline (27%; P=.017). Enthesis-Dextrose participants' satisfaction was 6.7+/-3.2
      compared with Enthesis-Saline (4.7+/-4.1; P=.079) and Superficial-Saline (3.9+/
      3.1; P=.003). USPRS findings were not different between groups (P=.734).
      CONCLUSIONS: In participants with painful rotator cuff tendinopathy who receive
      physical therapy, injection of hypertonic dextrose on painful entheses resulted
      in superior long-term pain improvement and patient satisfaction compared with
      blinded saline injection over painful entheses, with intermediate results for
      entheses injection with saline. These differences could not be attributed to a
      regenerative effect. Dextrose prolotherapy may improve on the standard care of
      painful rotator cuff tendinopathy for certain patients.

PMID- 26301386
TI  - Cross-Sectional Study of Bowel Symptoms in Adults With Cerebral Palsy: Prevalence
      and Impact on Quality of Life.
AB  - OBJECTIVES: To determine the prevalence and type of bowel symptoms, and their
      impact on health-related quality of life (HRQOL) in adults with cerebral palsy
      (CP). DESIGN: Prospective cross-sectional study. SETTING: Urban, outpatient
      rehabilitation facility. PARTICIPANTS: Adults with CP (N=91; 46 men, 45 women;
      mean age, 36y; age range, 18-79y). INTERVENTION: Not applicable. MAIN OUTCOME
      MEASURES: Participants were interviewed using standardized instruments to assess
      the frequency and types of bowel dysfunction. The International Consultation of
      Incontinence Questionnaire-Bowel was used to assess bowel incontinence and impact
      on quality of life, and constipation presence was determined using the Rome III
      criteria for constipation. Constipation symptoms were rated by the Patient
      Assessment of Constipation-Symptom Scale. Participants' mobility status was
      classified using the Gross Motor Function Classification System (GMFCS).
      Interactions between mobility measures, anthropometric measures, and bowel
      symptoms were assessed. RESULTS: Of the 91 participants enrolled, 62.6% were
      GMFCS IV or V. Twenty-eight participants (30.8%) reported severe difficulty with
      control of liquid stool (rating never or rarely); these participants were more
      likely to have a greater GMFCS level (P=.0004). Twenty-six participants (28.6%)
      reported that bowel function caused embarrassment some/most/all of the time.
      Fifty-nine participants (64.8%) met criteria for chronic constipation, which did
      not differ by GMFCS levels. Overall, 57.1% of participants reported that bowel
      symptoms interfered with life; 40.7% reported moderate to severe interference.
      CONCLUSIONS: Bowel symptoms were frequent, a source of embarrassment, and
      impacted HRQOL in these adults with CP. Addressing bowel-related symptoms has the
      potential to improve HRQOL in these adults.

PMID- 26301387
TI  - Self-Awareness of Falls Risk Among Elderly Patients: Characterizing Awareness
      Deficits and Exploring Associated Factors.
AB  - OBJECTIVE: To characterize self-awareness in older adults undergoing inpatient
      rehabilitation and explore factors associated with reduced awareness of falls
      risk. DESIGN: Prospective, cross-sectional design. SETTING: Older adult inpatient
      rehabilitation setting. PARTICIPANTS: Rehabilitation inpatients (N=91; mean age,
      77.97+/-8.04y) and their treating physiotherapist. INTERVENTIONS: None. MAIN
      OUTCOME MEASURES: Three aspects of self-awareness (intellectual, emergent,
      anticipatory) were measured using the Self-Awareness of Falls Risk Measure.
      Demographic, medical, and cognitive (Mini-Mental State Examination) information
      were collected. Current ability was measured using the FIM and timed Up and Go
      test. RESULTS: Of the patients in the sample, 31% to 63% underestimated falls
      risk and 3% to 10% overestimated falls risk depending on the aspect of awareness
      measured. Different aspects of reduced self-awareness were correlated with being
      a man, higher educational attainment, neurologic history, lower cognitive
      ability, and lower functional ability. Regression analysis indicated that sex
      (beta=-.33, P=.004), education (beta=-.30, P=.006), and neurologic history (beta=
      .22, P=.038) were independently associated with overall self-awareness.
      CONCLUSIONS: The results suggest that a proportion of older adults undergoing
      inpatient rehabilitation underestimate personal falls risk. Further research is
      required to investigate the contributors to and effects of reduced self-awareness
      of falls risk. Greater understanding of these factors will facilitate the
      development of strategies to increase awareness of falls risk and increase
      engagement in falls prevention.

PMID- 26301389
TI  - Cognitive linguistics.
AB  - Cognitive linguistics is one of the fastest growing and influential perspectives
      on the nature of language, the mind, and their relationship with sociophysical
      (embodied) experience. It is a broad theoretical and methodological enterprise,
      rather than a single, closely articulated theory. Its primary commitments are
      outlined. These are the Cognitive Commitment-a commitment to providing a
      characterization of language that accords with what is known about the mind and
      brain from other disciplines-and the Generalization Commitment-which represents a
      dedication to characterizing general principles that apply to all aspects of
      human language. The article also outlines the assumptions and worldview which
      arises from these commitments, as represented in the work of leading cognitive
      linguists. WIREs Cogn Sci 2012, 3:129-141. doi: 10.1002/wcs.1163 For further
      resources related to this article, please visit the WIREs website. 

PMID- 26301388
TI  - Clinical and Serological Dynamics of Besnoitia besnoiti Infection in Three
      Endemically Infected Beef Cattle Herds.
AB  - The dynamics of bovine besnoitiosis were studied in an area where the disease is
      endemic. A four-year longitudinal study was conducted for the first time in three
      infected beef cattle herds located in the Urbasa-Andia Mountains (Navarra,
      Spain). Each herd was visited four to seven times, and clinical and serological
      prevalence rates and incidence rates were estimated. Clinical inspections to
      identify compatible clinical signs with the disease stages were conducted at the
      beginning and end of the study. Serological assessment was initially performed by
      ELISA. Seronegative animals with clinical signs and seropositive animals with
      relative index per cent (RIPC) values lower than 30 that did not increase during
      the study period were analysed by Western blot to optimize the sensitivity and
      specificity of the ELISA test. Clinical prevalence rates were slightly higher
      (62% on average) than the seroprevalence rates (50% on average), and tissue cysts
      located in the vestibulum vaginae and sclera were the most frequently detected
      clinical signs. The proportion of seropositive animals with clinical signs varied
      from 16.7% to 73.6% among the herds, and 17% of cattle with clinical signs proved
      to be seronegative by both serological tests. An average 22% serological
      incidence rate was also reported in addition to clinical incidence rates that
      varied from 12.5% to 16.7%. Additionally, parasitemia was investigated in the
      herd that showed the highest clinical and seroprevalence rates. Only one PCR
      positive blood sample was detected. Thus, the role that blood may play in
      parasite transmission needs to be further investigated. Infected herds maintained
      both high prevalence and incidence rates in the absence of control measures and a
      high number of parasite carriers. Finally, economic impact studies on
      reproductive and productive losses associated with besnoitiosis need to be
      performed to implement a cost-benefit control programme.

PMID- 26301390
TI  - Neuroethics.
AB  - Neuroethics is a new sub-discipline of philosophy, with two broad focuses. The
      first, which has come to be called the ethics of neuroscience, concerns the
      assessment of ethical issues arising from neuroscience, its practice and its
      applications; the second, which has come to be called the neuroscience of ethics,
      concerns the ways in which the sciences of the mind can illuminate longstanding
      issues within philosophy. Especially in its guise as the neuroscience of ethics,
      neuroethics cannot sharply be distinguished from the naturalistic trend in
      philosophy which attempts to bring to bear data to the resolution of
      philosophical problems. It is distinctive only inasmuch as it is motivated by
      practical, and especially moral, concerns to a greater degree than empirical
      philosophy more generally. This article illustrates the practice and typical
      concerns of neuroethics with two case studies, one from each of its branches. The
      ethics of neuroscience is illustrated with the issue of cognitive enhancement,
      and the neuroscience of ethics is illustrated by discussion of free will. With
      regard to both issues, neuroethicists hope to advance beyond intuition and
      armchair argument by careful attention to the data emerging from the cognitive
      sciences. WIREs Cogn Sci 2012, 3:143-151. doi: 10.1002/wcs.1157 For further
      resources related to this article, please visit the WIREs website. 

PMID- 26301391
TI  - Rethinking the language of thought.
AB  - In this piece, we overview the language of thought (LOT) program, a currently
      influential theory of the computational nature of thought. We focus on LOT's
      stance on concepts, computation in the central system, and mental symbols. We
      emphasize certain longstanding problems arising for the LOT approach, suggesting
      resolutions to these problems. Many of the solutions involve departures from the
      standard LOT program, i.e., the LOT program as developed by Jerry Fodor. We close
      by identifying avenues for future work. WIREs Cogn Sci 2012, 3:153-162. doi:
      10.1002/wcs.1155 For further resources related to this article, please visit the
      WIREs website. 

PMID- 26301392
TI  - Object-based attention: strategy versus automaticity.
AB  - This article begins with a description of space- and object-based guidance of
      attentional selection. It goes on to discuss the most influential, two-rectangle,
      paradigm for demonstrating the existence of space- and object-based attentional
      effects. The article then considers two different mechanisms, attentional
      spreading and attentional prioritization, that can potentially explain how object
      representations come to guide attentional selection. Finally, it discusses
      several empirical findings that have emerged in support of the two different
      mechanisms. It concludes by putting forth a new framework for investigating
      object-based effects. WIREs Cogn Sci 2012, 3:163-169. doi: 10.1002/wcs.1162 For
      further resources related to this article, please visit the WIREs website. 

PMID- 26301393
TI  - Mechanisms of cerebellar contributions to cognition in humans.
AB  - The role of the human cerebellum in cognitive processes is the subject of ongoing
      debate. On the basis of neuroanatomical findings of closed cerebro-cerebellar
      loops in monkeys, which originate not only in motor but also in nonmotor regions
      of the cerebral cortex, this article addresses mechanisms of the involvement of
      the human cerebellum in two well-studied cognitive domains, executive function,
      working memory in particular, and associative learning, with special emphasis on
      the nature of a potential cerebellar contribution to these cognitive processes.
      The uniform organization of cortico-cerebellar connections suggests parallels in
      cerebellar information processing in motor- and nonmotor contexts. Taking into
      account recent models on cerebellar function, it is suggested that the main
      contribution of the cerebellum to motor as well as to cognitive tasks may be to
      provide accurate predictions of future sensations, actions, and events. WIREs
      Cogn Sci 2012, 3:171-184. doi: 10.1002/wcs.1161 For further resources related to
      this article, please visit the WIREs website. 

PMID- 26301394
TI  - Syntax acquisition.
AB  - Every normal child acquires a language in just a few years. By 3- or 4-years-old,
      children have effectively become adults in their abilities to produce and
      understand endlessly many sentences in a variety of conversational contexts.
      There are two alternative accounts of the course of children's language
      development. These different perspectives can be traced back to the nature versus
      nurture debate about how knowledge is acquired in any cognitive domain. One
      perspective dates back to Plato's dialog 'The Meno'. In this dialog, the
      protagonist, Socrates, demonstrates to Meno, an aristocrat in Ancient Greece,
      that a young slave knows more about geometry than he could have learned from
      experience. By extension, Plato's Problem refers to any gap between experience
      and knowledge. How children fill in the gap in the case of language continues to
      be the subject of much controversy in cognitive science. Any model of language
      acquisition must address three factors, inter alia: 1. The knowledge children
      accrue; 2. The input children receive (often called the primary linguistic data);
      3. The nonlinguistic capacities of children to form and test generalizations
      based on the input. According to the famous linguist Noam Chomsky, the main task
      of linguistics is to explain how children bridge the gap-Chomsky calls it a
      'chasm'-between what they come to know about language, and what they could have
      learned from experience, even given optimistic assumptions about their cognitive
      abilities. Proponents of the alternative 'nurture' approach accuse nativists like
      Chomsky of overestimating the complexity of what children learn, underestimating
      the data children have to work with, and manifesting undue pessimism about
      children's abilities to extract information based on the input. The modern
      'nurture' approach is often referred to as the usage-based account. We discuss
      the usage-based account first, and then the nativist account. After that, we
      report and discuss the findings of several studies of child language that have
      been conducted with the goal of helping to adjudicate between the alternative
      approaches to language development. WIREs Cogn Sci 2012, 3:185-203. doi:
      10.1002/wcs.1158 For further resources related to this article, please visit the
      WIREs website. 

PMID- 26301395
TI  - Computational models of syntactic acquisition.
AB  - The computational approach to syntactic acquisition can be fruitfully pursued by
      integrating results and perspectives from computer science, linguistics, and
      developmental psychology. In this article, we first review some key results in
      computational learning theory and their implications for language acquisition. We
      then turn to examine specific learning models, some of which exploit
      distributional information in the input while others rely on a constrained space
      of hypotheses, yet both approaches share a common set of characteristics to
      overcome the learning problem. We conclude with a discussion of how computational
      models connects with the empirical study of child grammar, making the case for
      computationally tractable, psychologically plausible and developmentally
      realistic models of acquisition. WIREs Cogn Sci 2012, 3:205-213. doi:
      10.1002/wcs.1154 For further resources related to this article, please visit the
      WIREs website. 

PMID- 26301396
TI  - Self model theory: learning from the future.
AB  - This paper synthesizes findings and theoretical propositions across behavioral,
      cognitive, and neuropsychological theories, with significant new
      conceptualizations bearing upon processes of learning and performance. There is a
      need to explain ultrarapid learning within the framework of cognitive science. In
      video self modeling and in challenging circumstances, the speed of behavior
      change appears to be derived from feedforward, in which component behaviors (in
      the repertoire) are reconfigured to produce a new skill or level of performance.
      It is argued that 'self modeling' is fundamental to learning, and peer/other
      modeling serves as an alternative. Learning in this way produces a cognitive self
      simulation which can be accessed to trigger a behavioral response in a future
      context. Related neurological processes are indicated by 'mental time travel'
      (MTT) and specific brain activity during the imagination (simulation) of future
      personal events. There is evidence that some brain mechanisms (mirror neurons),
      involved in immediate imitation, are differentially responsive to images of self
      versus other. MTT (to future events) in cognitive neuroscience has so far been
      discussed only in terms of prediction and planning not behavior change. These
      issues are brought together by self model theory. Conclusions drawn in this paper
      include discussions of the value in 'learning from the future' as a ubiquitous
      human ability. Overall, the propositions of this theory should stimulate diverse
      future research, linking neurological and behavioral contributions to cognitive
      science. WIREs Cogn Sci 2012, 3:215-230. doi: 10.1002/wcs.1156 For further
      resources related to this article, please visit the WIREs website. 

PMID- 26301397
TI  - Hippocampus.
AB  - Damage to the hippocampus and related brain regions causes a profound amnesic
      syndrome, in which patients are unable to form new memories about their
      experiences and about facts about the world. A number of theories have been
      proposed to explain hippocampal function. The theories that are currently most
      influential propose that the hippocampus is the substrate of declarative or
      episodic memory and that the hippocampus is the neural locus of a cognitive map.
      Anatomical, physiological, and behavioral studies of the hippocampal system have
      enabled a rich understanding of a number of general principles of information
      processing and storage in the brain. In this article, we describe key anatomical
      and physiological features of hippocampal function as well as the most
      influential theories of hippocampal function. WIREs Cogn Sci 2012, 3:231-251.
      doi: 10.1002/wcs.1164 For further resources related to this article, please visit
      the WIREs website. 

PMID- 26301398
TI  - The many faces of empathy and their relation to prosocial action and aggression
      inhibition.
AB  - This article discusses the emotional reactions most commonly associated with
      empathy and their relation to prosocial or altruistic action, aggression
      inhibition, and understanding others. In What is Empathy?, I characterize the
      distinct emotional reactions most commonly associated with empathy: empathy,
      sympathy, personal distress, and emotional contagion. In Measures of Empathy, I
      discuss the most common measures of dispositional and situational empathy. In
      Empathy, Prosocial Action, and Altruism, I consider the evidence that empathy,
      sympathy, and personal distress induce prosocial motivation. I conclude that
      sympathy is most strongly associated with prosocial, even altruistic, motivation.
      In Empathy and Aggression Inhibition, I examine the evidence that empathy
      inhibits aggression. The evidence is inconclusive. In Empathy and Mindreading, I
      briefly discuss empathy and mindreading, with an eye toward recent evidence
      concerning mirror neurons. I conclude by linking our current understanding of
      empathy to the philosophical tradition, and by offering some speculative remarks.
      WIREs Cogn Sci 2012, 3:253-263. doi: 10.1002/wcs.1165 For further resources
      related to this article, please visit the WIREs website. 

PMID- 26301399
TI  - Philosophical issues about concepts.
AB  - In this article, we review some important controversies about concepts in the
      philosophy of psychology, focusing particularly on the theories of concepts
      developed in philosophy, on the debate about the homogeneity of concepts, on neo
      empiricism, and on concept learning. WIREs Cogn Sci 2012, 3:265-279. doi:
      10.1002/wcs.1166 For further resources related to this article, please visit the
      WIREs website. 

PMID- 26301401
TI  - Diagnostic Delay and Amniotic Membrane Transplantation in a Child With Atypical
      Stevens-Johnson Syndrome.
AB  - A 4-year-old boy presented with a 6-day history of severe non-limbic-sparing
      conjunctivitis. Atypical Stevens-Johnson syndrome with a possible cause of
      Mycoplasma pneumoniae was suspected as the precipitant of the clinical symptoms.
      The patient recovered with amniotic membrane transplantation and intravenous
      immunoglobulin therapy despite an initial delay in diagnosis.

PMID- 26301405
TI  - Molecular Dynamics Simulations of the Interaction of Beta Cyclodextrin with a
      Lipid Bilayer.
AB  - Beta cyclodextrin (betaCD) is well-known as a potent drug carrier improving drug
      solubility, stability, and bioavailability. The water layer adjacent to the
      membrane surface and lipophilic domain itself are a controlling barrier for drug
      transport. However, the molecular details of the interaction between betaCD and
      the lipid membrane has not yet been clearly explained. Here, molecular dynamics
      simulations were performed to visualize the interaction process of the betaCD
      molecule with the lipid bilayer for six microseconds in total. Our results show
      that betaCD passively diffuses into the lipid bilayer by pointing its open
      secondary rim toward the lipid polar groups and then remains at the phosphate and
      glycerol-ester groups with hydrogen bond formation. The information obtained from
      this study may suggest that the association of betaCD at the cellular membrane
      plays an important role for the transfer of drug and the extraction of
      cholesterol. 

PMID- 26301404
TI  - Chitooligosaccharides as novel ingredients of fermented foods.
AB  - Chitooligosaccharides (COSs) have been clinically evaluated for their
      immunostimulating effects after oral intake. Similar to dietary supplements,
      prebiotics and biopreservatives, these water-soluble bioactives are easily
      incorporated into dairy products and beverages. Notwithstanding, the use of COS
      in fermented foods would be limited by its antimicrobial properties. In order to
      study the interaction with yoghurts as a model of fermented food, the effects of
      COS on chemical composition, viability, morphology and metabolism of lactic acid
      bacteria, fatty acid profiles and conjugated linoleic acid (CLA) were assessed
      over 28 days and after chemical digestion. There were no significant differences
      between the nutritional composition of controls and yoghurts supplemented with
      concentrations up to 0.1% w/w of COS. However, the acidification of milk
      decreased at 0.5% (p < 0.05) and the formation of yoghurt failed at 3.0%, without
      affecting viable counts. Lipid hydrolysis of yoghurts supplemented with 0.1% COS
      was not affected by chemical digestion. No significant differences were found
      between CLA percentages of controls and supplemented yoghurts after digestion.
      Although the nutritional composition, fatty acids and viable counts were not
      significantly modified after COS supplementation, the present study shows that
      COS diminishes bacterial acidification at concentrations higher than 0.1%, thus
      limiting the amounts that could be added to yoghurt. 

PMID- 26301406
TI  - Propofol sedation with a target-controlled infusion pump and bispectral index
      monitoring system in elderly patients during a complex upper endoscopy procedure.
AB  - BACKGROUND AND AIMS: Although the usefulness of propofol sedation during
      endoscopic submucosal dissection (ESD) for gastric neoplasms was reported
      previously, information is limited on its use in elderly patients. We
      investigated the safety and efficacy of propofol sedation with a target
      controlled infusion (TCI) pump and bispectral index (BIS) monitoring system
      (TCI/BIS system) in elderly patients during gastric ESD. METHODS: Included were
      413 consecutive gastric ESD procedures involving 455 lesions (379 patients)
      performed in patients under propofol sedation with a TCI/BIS system between
      October 2009 and September 2013. Patients were divided into 3 groups: group A,
      age <70 years (n = 162); group B, age >=70 and <80 years (n = 171); and group C,
      age >=80 years (n = 80). We compared the propofol dose and adverse events (eg,
      hypotension and hypoxemia) during ESD. RESULTS: Older groups required a lower
      target concentration of propofol (group A: median 2.1 MUg/mL [interquartile range
      (IQR), 1.9-2.3]; group B: median 1.6 MUg/mL [IQR, 1.3-1.8]; and group C: median
      1.4 MUg/mL [IQR, 1.2-1.6]; P < .0001). Hypotension tended to occur in the younger
      group, and hypoxemia occurred at a significantly higher rate in the older groups,
      although the number of cases was small. Low preoperative systolic blood pressure
      (<=125 mm Hg) was associated with hypotension (odds ratio [OR], 1.73; 95%
      confidence interval [CI], 1.12-2.70; P = .013) and abnormal pulmonary function
      was associated with hypoxemia in groups B and C (OR, 4.54; 95% CI, 1.01-31.5; P =
      .048). CONCLUSIONS: Elderly patients required lower doses of propofol with the
      TCI/BIS system than younger patients. Attention to hypoxemia is necessary in
      elderly patients, particularly patients with abnormal pulmonary function.

PMID- 26301407
TI  - EUS-guided liver biopsy provides diagnostic samples comparable with those via the
      percutaneous or transjugular route.
AB  - BACKGROUND AND AIMS: Liver biopsy (LB) traditionally has been performed via a
      percutaneous (PC), transjugular (TJ), or surgical approach. EUS-guided LB (EUS
      LB) is an emerging method that has shown promise in terms of tissue yield and
      procedural safety. Comparison of histologic yield of EUS-LB with other methods of
      LB has not been done. This study aimed to compare tissue yield of different LB
      methods. METHODS: EUS-LB, TJ-LB, and PC-LB were identified retrospectively. EUS
      LB was obtained via transgastric and transduodenal biopsy, or via transgastric
      (left lobe) biopsy alone using a 19-gauge FNA needle (non-Trucut). TJ-LB
      specimens were obtained with an 18- or 19-gauge needle, and PC-LB specimens with
      an 18- or 20-gauge needle. Stained slides were digitized on a whole slide
      scanner, and the total specimen length (TSL) and the count of complete portal
      triads (CPTs) were determined. Comparisons of TSL and CPT among the 3 groups were
      done with Wilcoxon rank sum tests. RESULTS: Wilcoxon rank sum tests indicated
      that EUS-LB of both liver regions produced significantly more tissue in terms of
      both TSL and CPTs compared with a PC-LB (P = .0000 and .0006). EUS-LB produced
      significantly longer TSL than TJ-LB (P = .01) and similar CPTs (P = .22). Those
      EUS-LB cases in which the left lobe only was sampled were not statistically
      different compared with PC-LB and TJ-LB. CONCLUSION: EUS-guided-LB produces
      specimens at least comparable to, and in some cases better than, PC-LB or TJ-LB.
      Widely separated liver regions can be easily sampled, which may have some
      benefit. The role of EUS-LB is likely to increase in the future.

PMID- 26301408
TI  - Adverse events of EUS-guided FNA of pancreatic cystic and solid lesions by using
      the lexicon proposed in an ASGE workshop: a prospective and comparative study.
AB  - BACKGROUND AND AIMS: Pancreatic cysts and solid lesions are routinely examined by
      EUS-guided FNA (EUS-FNA). The aim of this study was to compare the incidence of
      adverse events (AEs) of this procedure by using the lexicon recommended by the
      American Society for Gastrointestinal Endoscopy (ASGE). METHODS: This was a
      prospective and comparative study of patients who underwent EUS-FNA in which a 22
      gauge needle was used. In the pancreatic cystic lesions group (group I), complete
      fluid evacuation in a single needle pass was attempted, and ciprofloxacin was
      given during the procedure and for 3 days after. In the pancreatic solid lesions
      group (group II), the number of passes was determined by the on-site evaluation
      of the sample. AEs were defined and graded according to the lexicon recommended
      by the ASGE. Patients were followed for 48 hours, 1 week, and 1 month after the
      procedure. RESULTS: A total of 146 patients were included, 73 in group I and 73
      in group II. Potential factors influencing the incidence of AEs (ie, access route
      for FNA) were similar in both groups. AEs occurred in 5 of 146 patients (3.4%;
      95% confidence interval [CI], 1.3%-8%): 4 in group I (5.5%; 95% CI, 1.7%-13.7%)
      and 1 in group II (1.4%; 95% CI, -0.5% to 8.1%) (P = .03). Severity was mild in 1
      of 5 patients (20%) and moderate in 3 of 5 patients (60%). One patient with a
      solid mass in the head of the pancreas had a duodenal perforation after EUS and
      died after surgery. All other AEs occurred in the first 48 hours and resolved
      with medical therapy. There were 3 incidents of transient hypoxia and self
      limited abdominal pain in 1 and 2 patients, respectively. No patients were lost
      to follow-up. CONCLUSION: EUS-FNA of pancreatic cysts has an AEs rate similar to
      that of solid pancreatic masses, which is small enough to consider this procedure
      a safe and effective method for managing patients with both types of lesions. AEs
      occurred early after EUS-FNA, and patients should be closely followed during the
      first 2 days after the procedure.

PMID- 26301409
TI  - Reply by Authors.

PMID- 26301410
TI  - Editorial Comment.

PMID- 26301411
TI  - GLT-1 Transport Stoichiometry Is Constant at Low and High Glutamate
      Concentrations when Chloride Is Substituted by Gluconate.
AB  - Glutamate is the major excitatory neurotransmitter, but prolonged exposure even
      at micromolar concentrations causes neuronal death. Extracellular glutamate is
      maintained at nanomolar level by glutamate transporters, which, however, may
      reverse transport and release glutamate. If and when the reverse occurs depends
      on glutamate transport stoichiometry (GTS). Previously we found that in the
      presence of chloride, the coupled GLT-1 glutamate transporter current and its
      relationship to radiolabeled glutamate flux significantly decreased when
      extracellular glutamate concentration increased above 0.2 mM, which implies a
      change in GTS. Such high concentrations are feasible near GLT-1 expressed close
      to synaptic release site during excitatory neurotransmission. The aim of this
      study was to determine GLT-1 GTS at both low (19-75 MUM) and high (300-1200 MUM)
      glutamate concentration ranges. GTS experiments were conducted in the absence of
      chloride to avoid contributions by the GLT-1 uncoupled chloride conductance.
      Mathematical analysis of the transporter thermodynamic equilibrium allowed us to
      derive equations revealing the number of a particular type of ion transported per
      elementary charge based on the measurements of the transporter reversal
      potential. We found that GLT-1a expressed in COS-7 cells co-transports 1.5 Na+,
      0.5 Glu-, 0.5 H+ and counter-transports 0.6 K+ per elementary charge in both
      glutamate concentration ranges, and at both 37 degrees C and 26 degrees C
      temperatures. The thermodynamic parameter Q10 = 2.4 for GLT-1 turnover rate of 19
      s-1 (37 degrees C, -50 mV) remained constant in the 10 MUM-10 mM glutamate
      concentration range. Importantly, the previously reported decrease in the
      current/flux ratio at high glutamate concentration was not seen in the absence of
      chloride in both COS-7 cells and cultured rat neurons. Therefore, only in the
      absence of chloride, GLT-1 GTS remains constant at all glutamate concentrations.
      Possible explanations for why apparent GTS might vary in the presence of chloride
      are discussed. 

PMID- 26301413
TI  - Effects of Acid Treatment on Dental Zirconia: An In Vitro Study.
AB  - The aim of this study was to evaluate the effects of hydrofluoric (HF) acid,
      acetic acid, and citric acid treatments on the physical properties and structure
      of yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) at ambient
      temperature. In total, 110 bar-shaped zirconia specimens were randomly assigned
      to 11 groups. The specimens in the control group (C) received no surface
      treatment, while those in the Cage group were hydrothermally aged at 134 degrees
      C and 0.2 MPa for 20 h. Ten specimens each were immersed at ambient temperature
      in 5% and 40% HF acid for 2 h (40HF0), 1 day (5HF1, 40HF1), and 5 days (5HF5,
      40HF5), while 10 each were immersed at ambient temperature in 10% acetic acid and
      20% citric acid for 7 (AC7, CI7) and 14 days (AC14, CI14). X-ray diffraction
      (XRD) was used to quantitatively estimate the monoclinic phase. Furthermore,
      flexural strength, surface roughness, and surface Vickers hardness were measured
      after treatment. Scanning electron microscopy (SEM) was used to characterize the
      surface morphology. The Cage group specimens exhibited an increased monoclinic
      phase and flexural strength. Furthermore, 40% HF acid immersion decreased the
      flexural strength and surface hardness and deteriorated the surface finish, while
      5% HF acid immersion only decreased the surface hardness. All the HF acid
      immersed specimens showed an etched surface texture on SEM observations, while
      the other groups did not. These findings suggest that the treatment of Y-TZP with
      40% HF acid at ambient temperature causes potential damage, while treatment with
      5% HF acid, acetic acid, and citric acid is safe. 

PMID- 26301412
TI  - A Single Nucleotide Polymorphism in Catalase Is Strongly Associated with Ovarian
      Cancer Survival.
AB  - Ovarian cancer is the deadliest of all gynecologic cancers. Recent evidence
      demonstrates an association between enzymatic activity altering single nucleotide
      polymorphisms (SNP) with human cancer susceptibility. We sought to evaluate the
      association of SNPs in key oxidant and antioxidant enzymes with increased risk
      and survival in epithelial ovarian cancer. Individuals (n = 143) recruited were
      divided into controls, (n = 94): healthy volunteers, (n = 18), high-risk BRCA1/2
      negative (n = 53), high-risk BRCA1/2 positive (n = 23) and ovarian cancer cases
      (n = 49). DNA was subjected to TaqMan SNP genotype analysis for selected oxidant
      and antioxidant enzymes. Of the seven selected SNP studied, no association with
      ovarian cancer risk (Pearson Chi-square) was found. However, a catalase SNP was
      identified as a predictor of ovarian cancer survival by the Cox regression model.
      The presence of this SNP was associated with a higher likelihood of death (hazard
      ratio (HR) of 3.68 (95% confidence interval (CI): 1.149-11.836)) for ovarian
      cancer patients. Kaplan-Meier survival analysis demonstrated a significant median
      overall survival difference (108 versus 60 months, p<0.05) for those without the
      catalase SNP as compared to those with the SNP. Additionally, age at diagnosis
      greater than the median was found to be a significant predictor of death (HR of
      2.78 (95% CI: 1.022-7.578)). This study indicates a strong association with the
      catalase SNP and survival of ovarian cancer patients, and thus may serve as a
      prognosticator. 

PMID- 26301414
TI  - Relationships between Micro-Vascular and Iodine-Staining Patterns in the Vicinity
      of the Tumor Front of Superficial Esophageal Squamous Carcinoma.
AB  - OBJECTIVE: The aim of the present study was to clarify differences between micro
      vascular and iodine-staining patterns in the vicinity of the tumor fronts of
      superficial esophageal squamous cell carcinomas (ESCCs). METHODS: Ten consecutive
      patients with ESCCs who were treated by endoscopic submucosal dissection (ESD)
      were enrolled. At the edge of the iodine-unstained area, we observed 183 sites in
      total using image-enhanced magnifying endoscopy. We classified the micro-vascular
      and iodine-staining patterns into three types: Type A, in which the line of
      vascular change matched the border of the iodine-unstained area; Type B, in which
      the border of the iodine-unstained area extended beyond the line of vascular
      change; Type C, in which the line of vascular change extended beyond the border
      of the iodine-unstained area. Then, by examining histopathological sections, we
      compared the diameter of intra-papillary capillary loops (IPCLs) in cancerous
      areas and normal squamous epithelium. RESULTS: We investigated 160 sites that the
      adequate quality of pictures were obtained. There was no case in which the line
      of vascular change completely matched the whole circumference of the border of an
      iodine-unstained area. Among the 160 sites, type A was recognized at 76 sites
      (47.5%), type B at 79 sites (49.4%), and type C at 5 sites (3.1%). Histological
      examination showed that the mean diameter of the IPCLs in normal squamous
      epithelium was 16.2+/-3.7 MUm, whereas that of IPCLs in cancerous lesions was
      21.0+/-4.4 MUm. CONCLUSIONS: The development of iodine-unstained areas tends to
      precede any changes in the vascularity of the esophageal surface epithelium.

PMID- 26301416
TI  - Low Incidence of Renal Dysfunction among HIV-Infected Patients on a Tenofovir
      Based First Line Antiretroviral Treatment Regimen in Myanmar.
AB  - BACKGROUND: Since 2004, Medecins Sans Frontieres-Switzerland has provided
      treatment and care for people living with HIV in Dawei, Myanmar. Renal function
      is routinely monitored in patients on tenofovir (TDF)-based antiretroviral
      treatment (ART), and this provides an opportunity to measure incidence and risk
      factors for renal dysfunction. METHODS: We used routinely collected program data
      on all patients aged >=15 years starting first-line TDF-based ART between January
      2012 and December 2013. Creatinine clearance (CrCl) was assessed at base line and
      six-monthly, with renal dysfunction defined as CrCl < 50 ml/min/1.73 m2. We
      calculated incidence of renal dysfunction and used Cox regression analysis to
      identify associated risk factors. RESULTS: There were 1391 patients, of whom 1372
      had normal renal function at baseline. Of these, 86 (6.3%) developed renal
      dysfunction during a median time of follow-up 1.14 years with an incidence rate
      of 5.4 per 100 person-years: 78 had CrCl between 30-50 ml/min/1.73 m2 and were
      maintained on TDF-based ART, but 5 were changed to another regimen: 4 because of
      CrCl <30 ml/min/1.73 m2. Risk factors for renal dysfunction included age >=45
      years, diagnosed diabetes, underlying renal disease, underweight and CD4 count
      <200 cells/mm3. There were 19 patients with baseline renal dysfunction and all
      continued on TDF-based ART: CrCl stayed between 30-49 ml/min/1.73 m2 in five
      patients while the remainder regained normal renal function. CONCLUSIONS: In a
      resource-poor country like Myanmar, the low incidence of renal toxicity in our
      patient cohort suggests that routine assessment of CrCl may not be needed and
      could be targeted to high risk groups if resources permit.

PMID- 26301418
TI  - Transposon-based reprogramming to induced pluripotency.
AB  - Induced pluripotent stem (iPS) cells represent a recent innovation in the field
      of stem cells. Commonly, iPS cells are generated by viral transduction of core
      reprogramming genes, such as Oct4, Sox2, Klf4, c-Myc, Nanog and Lin28. However,
      integrating viruses, like retro- and lentiviral vectors, may cause insertional
      mutagenesis and may increase the risk of tumor formation. Therefore, alternative
      methods which avoid these safety concerns are intensively investigated. Here, we
      review the current status of transposon-based methods to induce pluripotency. DNA
      transposons are non-viral elements, which can be effectively integrated into a
      genome by their corresponding transposase enzyme. The advantages of transposon
      based gene transfer are their increased safety, their large cargo capacity, their
      relatively simple design, and the availability of hyper-active and mutated
      transposase enzymes. For example, integration-deficient, excision-competent
      transposase variants allow the complete removal of the reprogramming transposon
      after successful reprogramming to obtain transposon-free reprogrammed cells.
      Transposon-based reprogramming will broaden the toolbox for iPS cell production
      and will advance the establishment of safe, non-viral methods. 

PMID- 26301415
TI  - MicroRNA-Sequence Profiling Reveals Novel Osmoregulatory MicroRNA Expression
      Patterns in Catadromous Eel Anguilla marmorata.
AB  - MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs that regulate
      gene expression by post-transcriptional repression of mRNAs. Recently, several
      miRNAs have been confirmed to execute directly or indirectly osmoregulatory
      functions in fish via translational control. In order to clarify whether miRNAs
      play relevant roles in the osmoregulation of Anguilla marmorata, three sRNA
      libraries of A. marmorata during adjusting to three various salinities were
      sequenced by Illumina sRNA deep sequencing methods. Totally 11,339,168,
      11,958,406 and 12,568,964 clear reads were obtained from 3 different libraries,
      respectively. Meanwhile, 34 conserved miRNAs and 613 novel miRNAs were identified
      using the sequence data. MiR-10b-5p, miR-181a, miR-26a-5p, miR-30d and miR-99a-5p
      were dominantly expressed in eels at three salinities. Totally 29 mature miRNAs
      were significantly up-regulated, while 72 mature miRNAs were significantly down
      regulated in brackish water (100/00 salinity) compared with fresh water (00/00
      salinity); 24 mature miRNAs were significantly up-regulated, while 54 mature
      miRNAs were significantly down-regulated in sea water (250/00 salinity) compared
      with fresh water. Similarly, 24 mature miRNAs were significantly up-regulated,
      while 45 mature miRNAs were significantly down-regulated in sea water compared
      with brackish water. The expression patterns of 12 dominantly expressed miRNAs
      were analyzed at different time points when the eels transferred from fresh water
      to brackish water or to sea water. These miRNAs showed differential expression
      patterns in eels at distinct salinities. Interestingly, miR-122, miR-140-3p and
      miR-10b-5p demonstrated osmoregulatory effects in certain salinities. In
      addition, the identification and characterization of differentially expressed
      miRNAs at different salinities can clarify the osmoregulatory roles of miRNAs,
      which will shed lights for future studies on osmoregulation in fish. 

PMID- 26301417
TI  - Methods to Develop an Electronic Medical Record Phenotype Algorithm to Compare
      the Risk of Coronary Artery Disease across 3 Chronic Disease Cohorts.
AB  - BACKGROUND: Typically, algorithms to classify phenotypes using electronic medical
      record (EMR) data were developed to perform well in a specific patient
      population. There is increasing interest in analyses which can allow study of a
      specific outcome across different diseases. Such a study in the EMR would require
      an algorithm that can be applied across different patient populations. Our
      objectives were: (1) to develop an algorithm that would enable the study of
      coronary artery disease (CAD) across diverse patient populations; (2) to study
      the impact of adding narrative data extracted using natural language processing
      (NLP) in the algorithm. Additionally, we demonstrate how to implement CAD
      algorithm to compare risk across 3 chronic diseases in a preliminary study.
      METHODS AND RESULTS: We studied 3 established EMR based patient cohorts: diabetes
      mellitus (DM, n = 65,099), inflammatory bowel disease (IBD, n = 10,974), and
      rheumatoid arthritis (RA, n = 4,453) from two large academic centers. We
      developed a CAD algorithm using NLP in addition to structured data (e.g. ICD9
      codes) in the RA cohort and validated it in the DM and IBD cohorts. The CAD
      algorithm using NLP in addition to structured data achieved specificity >95% with
      a positive predictive value (PPV) 90% in the training (RA) and validation sets
      (IBD and DM). The addition of NLP data improved the sensitivity for all cohorts,
      classifying an additional 17% of CAD subjects in IBD and 10% in DM while
      maintaining PPV of 90%. The algorithm classified 16,488 DM (26.1%), 457 IBD
      (4.2%), and 245 RA (5.0%) with CAD. In a cross-sectional analysis, CAD risk was
      63% lower in RA and 68% lower in IBD compared to DM (p<0.0001) after adjusting
      for traditional cardiovascular risk factors. CONCLUSIONS: We developed and
      validated a CAD algorithm that performed well across diverse patient populations.
      The addition of NLP into the CAD algorithm improved the sensitivity of the
      algorithm, particularly in cohorts where the prevalence of CAD was low.
      Preliminary data suggest that CAD risk was significantly lower in RA and IBD
      compared to DM.

PMID- 26301419
TI  - Insight into DNA Minor Groove Unspecific Binding of Pyrrole Polyamide.
AB  - Chemistry-based approaches have exploited base-pairing for sequence-specific
      recognition of DNA. A variety of sequence-specific Py-Im hairpin polyamides to
      target sequences of biological interest have been widely developed. Here we
      reported that an eight-ring N-methylpyrrole polyamide can induce a strong
      negative signal when it interacted with ct-DNA in the minor groove, which differs
      from the typical CD signal induced by hairpin polyamide reported previously. Our
      current efforts mainly focused on investigating possible reasons and binding mode
      by CD spectroscopy, singular value decomposition, and atomic force microscopy.
      The results suggested that partly compacted DNA may form due to the unfolded
      binding mode that made DNA shrink along the axis of duplex. In addition, this
      unfolded binding was remarkably restrained in high ionic strength medium where
      the neutralized phosphate groups in the DNA backbone narrowed the minor groove.
      The present work might help to understand deeply how the Py-Im polyamides bind to
      duplex DNA under different conditions and, in particular, be applied to gene
      manipulation and expression. 

PMID- 26301420
TI  - Nucleophilic Iododifluoromethylation of Aldehydes Using Bromine/Iodine Exchange.
AB  - A method for the iododifluoromethylation of aromatic aldehydes using
      (bromodifluoromethyl)trimethylsilane (Me3SiCF2Br) is described. The selective
      formation of the CF2I group is based on using sodium iodide, with the sodium
      serving as a scavenger of bromide and iodide serving as a nucleophile with
      respect to difluorocarbene. The primary CF2I-addition products can undergo HI
      elimination or iodine/zinc exchange followed by allylation in a one-pot manner. 

PMID- 26301421
TI  - Psychotherapists as gatekeepers: An evidence-based case study highlighting the
      role and process of letter writing for transgender clients.
AB  - In order to receive medically necessary gender-affirming treatments, transgender
      individuals are required to provide evidence of their readiness for gender
      transitioning. Most often, this evidence includes 1 letter for hormone therapy
      and 2 letters for surgery. According to the World Professional Association for
      Transgender Health (WPATH) Standards of Care (SOC), psychotherapists or other
      eligible health professionals are the only individuals qualified to write these
      letters. The present case study examined how psychotherapist gatekeeping and
      letter writing for a transgender client were intertwined with psychotherapy
      processes and outcomes. Over the course of 12 months of treatment, the client was
      assessed through 8 time points using multiple methods. Six of the assessments
      were conducted with validated outcome measures (baseline; Sessions 5, 10, 15, and
      20; and termination); 1 of the assessments was conducted as a clinical interview
      for letter-writing purposes and additional outcome measures (Session 8); and
      evaluating the process of letter writing was an aspect of psychotherapy (Session
      20). Symptom alleviation, improvement in psychological well-being, and increases
      in overall quality of life occurred from baseline to termination. Results
      indicate that psychotherapy assisted with the process of gender transitioning,
      which in turn improved client outcomes. Recommendations for writing letters for
      clients who desire a gender transition are included.

PMID- 26301422
TI  - A delay-discounting measure of preference for racial/ethnic matching in
      psychotherapy.
AB  - In this study, we sought to compare racial/ethnic minority participants'
      preference for racial/ethnic matching in psychotherapy with preferences for other
      methods of addressing cultural factors in treatment. Using a delay-discounting
      method, college students (331 racial/ethnic minority students from 2
      universities) and a nationwide sample of self-reported clients (n = 77) were
      asked to indicate their strength of preference for 4 different methods for
      addressing culturally related variables in psychotherapy, including a desire to
      (a) work with a therapist whose race/ethnicity matches their own, (b) work with a
      therapist with a high level of multicultural training and experience, (c) receive
      a culturally adapted treatment, and (d) receive a therapist who is also a member
      of a racial/ethnic minority group, but not the same as the participant (i.e., a
      racial/ethnic minority pairing). We found that participants were willing to make
      significant sacrifices in treatment efficacy in order to receive each of the
      variables tested. In both samples, preferences were significantly stronger for
      therapist multicultural training/experience and use of culturally adapted
      treatments compared with racial/ethnic matching and racial/ethnic minority
      pairing. Further analyses indicated that clients expressed stronger preferences
      for racial/ethnic match and minority pairing than college student participants,
      and preference strength for 3 of the 4 scenarios was significantly related to
      strength of minority culture identification. The results of this study have
      important implications for preference accommodation in psychotherapy with
      racial/ethnic minority individuals.

PMID- 26301423
TI  - Psychotherapist effects in meta-analyses: How accurate are treatment effects?
AB  - Psychotherapists are known to vary in their effectiveness with their clients, in
      randomized clinical trials as well as naturally occurring treatment settings. The
      fact that therapists matter has 2 effects in psychotherapy studies. First, if
      therapists are not randomly assigned to modalities (which is rare) this may bias
      the estimation of the treatment effects, as the modalities may have therapists of
      differing skill. In addition, if the data are analyzed at the client level (which
      is virtually always the case) then the standard errors for the effect sizes will
      be biased due to a violation of the assumption of independence. Thus, the
      conclusions of many meta-analyses may not reflect true estimates of treatment
      differences. We reexamined 20 treatment effects selected from 17 meta-analyses.
      We focused on meta-analyses that found statistically significant differences
      between treatments for a variety of disorders by correcting the treatment effects
      according to the variability in outcomes known to be associated with
      psychotherapists. The results demonstrated that after adjusting the results based
      on most small estimates of therapist effects, ~80% of the reported treatment
      effects would still be statistically significant. However, at larger estimates,
      only 20% of the treatment effects would still be statistically significant after
      controlling for therapist effects. Although some meta-analyses were consistent in
      their estimates for treatment differences, the degree of certainty in the results
      was considerably reduced after considering therapist effects. Practice
      implications for understanding treatment effects, namely, therapist effects, in
      meta-analyses and original studies are provided.

PMID- 26301424
TI  - Removing very low-performing therapists: A simulation of performance-based
      retention in psychotherapy.
AB  - Therapists can impact the likelihood a given patient will benefit from
      psychotherapy. However, therapists are rarely held accountable for their
      patients' outcomes. As a result, low-performing providers likely continue to
      practice alongside providers with high response rates. In the current study, we
      conducted a Monte Carlo simulation to illustrate a thought experiment-what
      happens to patient outcomes if therapists with the worst outcomes were removed
      from practice? We drew initial samples of 50 therapists from 3 simulated
      populations of 1,000 therapists with a mean patient response rate of 50% and
      different effect sizes for therapist variability in outcomes. We simulated 30
      patient outcomes for each therapist, with outcome defined as response to
      treatment versus no response. We removed therapists with response rates in the
      bottom 5% and replaced them with a random sample of therapists from the
      population. Over 10 years, the difference in responses between the lowest and
      highest performing therapists was substantial (between 697 and 997 additional
      responses to treatment). After repeatedly removing the lowest performing
      providers 40 times (simulating a 10-year time span), response rates increased
      substantially. The cumulative number of patient responses (i.e., summing the
      total number of responses across 10 years) increased by 4,266, 6,404, and 9,307
      when therapists accounted for 5%, 10%, or 20% of the patient outcome variance,
      respectively. These findings indicate that performance-based retention of
      therapists could improve the quality of psychotherapy in health systems by
      improving the average response rate and decreasing the probability that a patient
      will be treated by a therapist who consistently has poor outcomes.

PMID- 26301425
TI  - The role of deliberate practice in the development of highly effective
      psychotherapists.
AB  - Little empirical research exists about highly effective psychotherapists, and
      none about the factors that mediate the acquisition and maintenance of superior
      performance skills (e.g., Ericsson, 1996, 2006; Ericsson, Krampe, & Tesch-Romer,
      1993). In the full sample, a 3-level multilevel modeling (Level 1: clients; Level
      2: therapists; Level 3: organization types) of practitioner outcomes was used to
      examine the contribution of the therapist to treatment effectiveness. Consistent
      with prior research, in the full sample (n = 69 therapists; n = 4,580 clients) it
      was found that therapist effects explained 5.1% of the variance in outcome, after
      adjusting for initial severity. Therapist gender, caseload, and age were not
      found to be significant predictors. In a subsample of therapists, the
      relationship between outcome and therapist demographic variables, professional
      development activities, and work practices was analyzed (n = 17 therapists, n =
      1,632 clients). Therapist characteristics (e.g., years of experience, gender,
      age, profession, highest qualification, caseload, degree of theoretical
      integration) did not significantly predict client-reported outcomes. Consistent
      with the literature on expertise and expert performance, the amount of time spent
      targeted at improving therapeutic skills was a significant predictor of client
      outcomes. Further, highly effective therapists indicated requiring more effort in
      reviewing therapy recordings alone than did the rest of the cohort. Caveats and
      implications for clinical practice, continuing professional development, and
      training are discussed.

PMID- 26301426
TI  - Iron-, Cobalt-, and Nickel-Catalyzed Asymmetric Transfer Hydrogenation and
      Asymmetric Hydrogenation of Ketones.
AB  - Chiral alcohols are important building blocks in the pharmaceutical and fine
      chemical industries. The enantioselective reduction of prochiral ketones
      catalyzed by transition metal complexes, especially asymmetric transfer
      hydrogenation (ATH) and asymmetric hydrogenation (AH), is one of the most
      efficient and practical methods for producing chiral alcohols. In both academic
      laboratories and industrial operations, catalysts based on noble metals such as
      ruthenium, rhodium, and iridium dominated the asymmetric reduction of ketones.
      However, the limited availability, high price, and toxicity of these critical
      metals demand their replacement with abundant, nonprecious, and biocommon metals.
      In this respect, the reactions catalyzed by first-row transition metals, which
      are more abundant and benign, have attracted more and more attention. As one of
      the most abundant metals on earth, iron is inexpensive, environmentally benign,
      and of low toxicity, and as such it is a fascinating alternative to the precious
      metals for catalysis and sustainable chemical manufacturing. However, iron
      catalysts have been undeveloped compared to other transition metals. Compared
      with the examples of iron-catalyzed asymmetric reduction, cobalt- and nickel
      catalyzed ATH and AH of ketones are even seldom reported. In early 2004, we
      reported the first ATH of ketones with catalysts generated in situ from iron
      cluster complex and chiral PNNP ligand. Since then, we have devoted ourselves to
      the development of ATH and AH of ketones with iron, cobalt, and nickel catalysts
      containing novel chiral aminophosphine ligands. In our study, the iron catalyst
      containing chiral aminophosphine ligands, which are expected to control the
      stereochemistry at the metal atom, restrict the number of possible
      diastereoisomers, and effectively transfer chiral information, are successful
      catalysts for enantioselective reduction of ketones. Among these novel chiral
      aminophosphine ligands, 22-membered macrocycle P2N4 exhibited extraordinary
      enantioselectivities when combined with iron(0) cluster Fe3(CO)12. A broad scope
      of ketones including aromatic, heteroaromatic, and beta-ketoesters can be reduced
      smoothly with excellent enantioselectivities (up to 99% ee) approaching or
      exceeding those achievable with the noble metal catalysts. Notably, the chiral
      iron-based catalyst proved to be highly efficient for both ATH as well as AH of
      various ketones. Until now, such "universal" catalyst is very rare. Preliminary
      studies suggest that the AH reaction most likely involved iron particles as the
      active catalytic species. These research results point to a new direction in
      developing viable effective nonprecious metal catalysts for asymmetric reduction
      and probably for other asymmetric catalytic reactions as well. 

PMID- 26301427
TI  - Ribosome-Mediated Incorporation of Dipeptides and Dipeptide Analogues into
      Proteins in Vitro.
AB  - Plasmids containing 23S rRNA randomized at positions 2057-2063 and 2502-2507 were
      introduced into Escherichia coli, affording a library of clones which produced
      modified ribosomes in addition to the pre-existing wild-type ribosomes. These
      clones were screened with a derivative of puromycin, a natural product which acts
      as an analogue of the 3'-end of aminoacyl-tRNA and terminates protein synthesis
      by accepting the growing polypeptide chain, thereby killing bacterial cells. The
      puromycin derivative in this study contained the dipeptide p
      methoxyphenylalanylglycine, implying the ability of the modified ribosomes in
      clones sensitive to this puromycin analogue to recognize dipeptides. Several
      clones inhibited by the puromycin derivative were used to make S-30 preparations,
      and some of these were shown to support the incorporation of dipeptides into
      proteins. The four incorporated species included two dipeptides (Gly-Phe (2) and
      Phe-Gly (3)), as well as a thiolated dipeptide analogue (4) and a fluorescent
      oxazole (5) having amine and carboxyl groups approximately the same distance
      apart as in a normal dipeptide. A protein containing both thiolated dipeptide 4
      and a 7-methoxycoumarin fluorophore was found to undergo fluorescence quenching.
      Introduction of the oxazole fluorophore 5 into dihydrofolate reductase or green
      fluorescent protein resulted in quite strong enhancement of its fluorescence
      emission, and the basis for this enhancement was studied. The aggregate results
      demonstrate the feasibility of incorporating dipeptides as a single ribosomal
      event, and illustrate the lack of recognition of the central peptide bond in the
      dipeptide, potentially enabling the incorporation of a broad variety of
      structural analogues. 

PMID- 26301428
TI  - Impurities and Electronic Property Variations of Natural MoS2 Crystal Surfaces.
AB  - Room temperature X-ray photoelectron spectroscopy (XPS), inductively coupled
      plasma mass spectrometry (ICPMS), high resolution Rutherford backscattering
      spectrometry (HR-RBS), Kelvin probe method, and scanning tunneling microscopy
      (STM) are employed to study the properties of a freshly exfoliated surface of
      geological MoS2 crystals. Our findings reveal that the semiconductor 2H-MoS2
      exhibits both n- and p-type behavior, and the work function as measured by the
      Kelvin probe is found to vary from 4.4 to 5.3 eV. The presence of impurities in
      parts-per-million (ppm) and a surface defect density of up to 8% of the total
      area could explain the variation of the Fermi level position. High resolution RBS
      data also show a large variation in the MoSx composition (1.8 < x < 2.05) at the
      surface. Thus, the variation in the conductivity, the work function, and
      stoichiometry across small areas of MoS2 will have to be controlled during
      crystal growth in order to provide high quality uniform materials for future
      device fabrication. 

PMID- 26301429
TI  - Nickel(0)-Catalyzed Enantio- and Diastereoselective Synthesis of Benzoxasiloles:
      Ligand-Controlled Switching from Inter- to Intramolecular Aryl-Transfer Process.
AB  - A highly enantioselective synthesis of 3-aryl-, vinyl-, and alkynyl-2,1
      benzoxasiloles (up to 99.9% ee and 99% yield) was achieved via the sequential
      activation of an aldehyde and a silane by nickel(0). This strategy was applied to
      a simultaneous generation of carbon- and silicon-stereogenic centers with
      excellent selectivity (dr = 99:1) via diastereotopic aryl transfer. Initial
      mechanistic studies revealed the complete switching of an aryl-transfer process
      from an intermolecular (racemic synthesis in the presence of IPr) to an
      intramolecular (enantioselective synthesis using chiral NHC, L5) fashion. A
      plausible rationale for the switching of the aryl-transfer process is given by a
      preliminary DFT calculation, which suggests that the coordination of 1 to the
      nickel(0)/L5 fragment in an eta(2)-arene:eta(2)-aldehyde fashion would be a key
      to the intramolecular process, while the formation of the corresponding
      intermediate is not possible in the presence of IPr. Owing to the chemically
      labile nature of its C-Si and O-Si bonds, enantioenriched benzoxasiloles are
      utilized for the synthesis of chiral building blocks and antihistaminic and
      anticholinergic drug molecules such as (R)-orphenadrine and (S)-neobenodine with
      no erosion of the enantiomeric excess. 

PMID- 26301430
TI  - Facile Synthesis of Hierarchical Mesoporous Honeycomb-like NiO for Aqueous
      Asymmetric Supercapacitors.
AB  - Three-dimensional (3D) hierarchical nanostructures have been demonstrated as one
      of the most ideal electrode materials in energy storage systems due to the
      synergistic combination of the advantages of both nanostructures and
      microstructures. In this study, the honeycomb-like mesoporous NiO microspheres as
      promising cathode materials for supercapacitors have been achieved using a
      hydrothermal reaction, followed by an annealing process. The electrochemical
      tests demonstrate the highest specific capacitance of 1250 F g(-1) at 1 A g(-1).
      Even at 5 A g(-1), a specific capacitance of 945 F g(-1) with 88.4% retention
      after 3500 cycles was obtained. In addition, the 3D porous graphene (reduced
      graphene oxide, rGO) has been prepared as an anode material for supercapacitors,
      which displays a good capacitance performance of 302 F g(-1) at 1 A g(-1). An
      asymmetric supercapacitor has been successfully fabricated based on the honeycomb
      like NiO and rGO. The asymmetric supercapacitor achieves a remarkable performance
      with a specific capacitance of 74.4 F g(-1), an energy density of 23.25 Wh kg(
      1), and a power density of 9.3 kW kg(-1), which is able to light up a light
      emitting diode. 

PMID- 26301431
TI  - Endoscopic endonasal management of non-functioning pituitary adenomas with
      cavernous sinus invasion: a 10- year experience.
AB  - BACKGROUND: The management of Non-Functioning Pituitary Adenoma (NFPA) invading
      the cavernous sinus (CS) is currently a balancing act between the surgical
      decompression of neural structures, radiotherapy and a wait-and-see policy.
      METHODS: We undertook a retrospective review of 56 cases of NFPA with CS invasion
      treated through an endoscopic endonasal approach (EEA) between 2000 and 2010. The
      Knosp classification was adopted to describe CS involvement using information
      from preoperative MRI and intraoperative findings. Extent of resection and
      surgical outcomes were evaluated on the basis of postoperative contrast-enhanced
      MRI. Endocrinological improvement and visual outcomes were assessed according to
      the most recent consensus criteria. RESULTS: EEA was performed using direct para
      septal, trans-ethmoidal-sphenoidal or trans-ethmoidal-pterygoidal-sphenoidal
      approach. Visual outcomes improved in 30 (81%) patients. Normalization or at
      least improvement of previous hypopituitarism was obtained in 55% of cases. A
      gross total resection was achieved in 30.3% of cases. The recurrence-free
      survival was 87.5%, with a mean follow-up of 61 months (range, 36-166 months). No
      major intraoperative or postoperative complications occurred. DISCUSSION: EEA is
      a minimally-invasive, safe and effective procedure for the management of NFPA
      invading the CS. The extent of CS involvement was the main factor limiting the
      degree of tumor resection. The EEA was able to resolve the mass effect,
      preserving or restoring visual function, and obtaining adequate long-term tumor
      control.

PMID- 26301432
TI  - Control of Light Emission by a Plasmonic Crystal Cavity.
AB  - Surface plasmon-polaritons (SPPs) localized inside a plasmonic crystal (PlC)
      cavity are probed by STEM-CL technique to characterize the influence of the
      surface shape parameters on the cavity modes. The results elucidate the formation
      mechanism of the cavity mode in terms of the symmetry and quality factor, which
      provide a clear design guide for the PlC cavity to control the coupling between
      SPPs and photons in plasmonic devices and future integrated circuits. 

PMID- 26301433
TI  - Integration of a model-independent interface for RBE predictions in a treatment
      planning system for active particle beam scanning.
AB  - Especially for heavier ions such as carbon ions, treatment planning systems
      (TPSs) for ion radiotherapy depend on models predicting the relative biological
      effectiveness (RBE) of the particles involved. Such models are subject to
      intensive research and the choice of the optimal RBE model is a matter of debate.
      On the other hand TPSs are often strongly coupled to particular RBE models and
      transition even to extended models of the same family can be difficult. We
      present here a model-independent interface which allows the unbiased use of any
      RBE model capable of providing dose-effect curves (even sampled curves) for a
      TPS. The full decoupling between the RBE model and TPS is based on the beam
      mixing model proposed by Lam which is, in contrast to the often-used Zaider-Rossi
      model, independent of the explicit form of the underlying dose-effect curves.
      This approach not only supports the refinement of RBE models without adaptations
      of the TPS--which we demonstrate by means of the local effect model (LEM)--but
      also allows the comparison of very different model approaches on a common basis.
      We exemplify this by a comparison between the LEM and a model from the literature
      for proton RBE prediction.

PMID- 26301434
TI  - Versatile and Rapid Postfunctionalization from Cyclodextrin Modified Host
      Polymeric Membrane Substrate.
AB  - Surface modification has long been of great interest to impart desired
      functionalities to the bioimplants. However, due to the limitations of recent
      technologies in surface modification, it is highly desirable to explore novel
      protocols, which can advantageously and efficiently endow the inert material
      surfaces with versatile biofunctionalities. Herein, to achieve versatile and
      rapid postfunctionalization of polymeric membrane, we demonstrate a new strategy
      for the fabrication of beta-cyclodextrin (beta-CD) modified host membrane
      substrate that can recognize a series of well-designed guest macromolecules. The
      surface assembly procedure was driven by the host-guest interaction between
      adamantane (Ad) and beta-CD. beta-CD immobilized host membrane was fabricated via
      two steps: (1) epoxy groups enriched poly(ether sulfone) (PES) membrane was first
      prepared via in situ cross-linking polymerization and subsequently phase
      separation; (2) mono-6-deoxy-6-ethylenediamine-beta-CD (EDA-beta-CD) was then
      anchored onto the surface of the epoxy functionalized PES membrane to obtain PES
      CD. Subsequently, three types of Ad-terminated polymers, including Ad
      poly(styrenesulfonate-co-sodium acrylate) (Ad-PSA), Ad-methoxypoly(ethylene
      glycol) (Ad-PEG), and Ad-poly(methyl chloride-quaternized 2-(dimethylamino)ethyl
      methacrylate (Ad-PMT), were separately assembled onto the beta-CD immobilized
      surfaces to endow the membranes with anticoagulant, antifouling, and
      antibacterial capability, respectively. Activated partial thromboplastin time
      (APTT), thrombin time (TT), and prothrombin time (PT) measurements were carried
      out to explore the anticoagulant activity. The antifouling capability was
      evaluated via protein adsorption and platelet adhesion measurements. Moreover,
      Staphyllococcous aureus (S. aureus) was selected as model bacteria to evaluate
      the antibacterial ability of the functionalized membranes. The results indicated
      that well-regulated blood compatibility, antifouling capability, and bactericidal
      activity could be achieved by the proposed rapid postfunctionalization on
      polymeric membranes. This approach of versatile and rapid postfunctionalization
      is promising for the preparation of multifunctional polymeric membrane materials
      to meet with various demands for the further applications. 

PMID- 26301435
TI  - The Relationship Between Perceptions of Response to Disclosure of Childhood
      Sexual Abuse and Later Outcomes.
AB  - This study assessed whether perceptions of others' reactions to disclosure are
      related to psychological and physical outcomes among individuals with a history
      of child sexual abuse. Eighty-six female undergraduates completed a series of
      questionnaires assessing child sexual abuse, nonsexual trauma, depression,
      anxiety, posttraumatic stress disorder, somatic symptoms, disclosure, and social
      reactions to disclosure. Those who reported child sexual abuse endorsed higher
      levels of psychological and physical symptoms than those who reported a nonsexual
      traumatic event. Child sexual abuse survivors who reported more hurtful responses
      to disclosure had higher levels of posttraumatic stress disorder, anxiety, and
      physical symptoms than nonsexual trauma survivors. These findings suggest that
      many survivors of CSA may need psychological services, and an important focus of
      treatment may be assessing and strengthening social support. 

PMID- 26301436
TI  - Child Sexual Abuse, Sexual Anxiety, and Sexual Satisfaction: The Role of Self
      Capacities.
AB  - Research indicates that child sexual abuse produces lasting alterations in
      interpersonal relatedness, identity, and affect regulation, often referred to as
      self-capacity disturbance. Child sexual abuse also has been shown to negatively
      impact sexual functioning. This study examined the role of altered self
      capacities in mediating the relationship between child sexual abuse and sexual
      responses. Path analysis revealed that child sexual abuse was related to sexual
      anxiety and decreased sexual satisfaction through its association with reduced
      self-awareness and a propensity to be involved in difficult interpersonal
      relationships. 

PMID- 26301437
TI  - Experiences of Mothers Who Are Child Sexual Abuse Survivors: A Qualitative
      Exploration.
AB  - Child sexual abuse has been associated with a number of problems affecting women
      over their lifespan, including difficulties with parenting. However, there is a
      modest number of qualitative studies examining the impact of child sexual abuse
      on survivors who are mothers. There is a particular need for qualitative
      investigations that ask survivors who are mothers general questions about the
      impact of child sexual abuse on their lives rather than those that specifically
      ask about the impact of child sexual abuse on parenting. The former approach
      would allow survivors to describe effects that may impact parenting but that
      survivors do not consciously link to affecting their parenting. Such information
      may inform interventions to assist this population of survivors. This secondary
      data analysis examined themes revealed in interviews with 44 survivors of child
      sexual abuse who were mothers. Participants were seeking treatment for their
      child sexual abuse and completed an in-person interview in which they were asked
      open-ended questions about the sexual abuse they experienced as a child and how
      their abuse affects them now as adults. The interviews were recorded,
      transcribed, and coded using thematic analysis. The following six themes emerged
      from the narratives: (a) being a parent, (b) family of origin dysfunction, (c)
      the impact of abuse, (d) the abuse history and response to abuse, (e) coping, and
      (f) hopes and desires for the future. This study highlights several ways in which
      child sexual abuse impacts survivors who are mothers, areas for further study,
      and the need for interventions to assist this population in meeting the
      challenges they face as mothers. 

PMID- 26301438
TI  - A Single-Case Study of Resiliency After Extreme Incest in an Old Order Amish
      Family.
AB  - This exploratory research brief presents a single case study of the resiliency of
      "Mary B." She grew up in an Old Order Amish family where isolation, secrecy, and
      patriarchy masked repeated sexual assaults by her older brothers that began at
      age 7. By the age of 20, Mary alleged she had been raped on more than 200
      separate occasions by members of her Amish family. After years of pleading with
      her mother and church officials to intervene, she sought therapy outside the
      Amish community. This led to three of her brothers being incarcerated. Her family
      disowned her and she was banned from the Amish community, leaving with an 8th
      grade education and little more than the clothes she was wearing. In less than 2
      years, Mary had moved to a new town, completed her GED, obtained a car and
      driving license, maintained a small home, and worked as a certified nursing
      assistant. She consented to tape recorded interviews and completed several
      quantitative diagnostic measures. Scores on the diagnostic measures placed her
      within the normal range on self-esteem, competency, depression, stress, social
      support, and life skills. Analysis of interviews revealed Mary rebounded from her
      past by reframing her experiences. Themes identified within the interviews
      supported 6 of the 7 types of resiliencies (insight, independence, initiative,
      relationships, humor, and morality) outlined in the therapeutic Challenge Model. 

PMID- 26301439
TI  - Sexual Offenses Among Children in the North of Jordan: An Exploratory Study.
AB  - Sexual offenses are an important global health problem threatening people of all
      age groups. There are no reported studies regarding sexual violence among
      children in Jordan. Therefore, this study aimed to examine the problem of sexual
      violence among children in the Northern region of Jordan. A retrospective design
      was adopted to review all reports from the Forensic Medicine Teaching Center of
      North of Jordan clinic on cases of sexual-related assaults that occurred between
      2003 and 2007. Reports were reviewed for age, gender, toxicological analysis, and
      relevant information provided by victims and their relatives. Results indicated
      that 53% of the cases were male victims, with a male to female ratio of 1:1. Ages
      ranged from 3 to 18 years with a mean age of 12.5 years. Most cases were
      considered indecent assaults, while 37.1% were cases of rape. In most cases,
      offenders were strangers. It could be concluded that Jordanian children are as
      susceptible to sexual assaults as their counterparts worldwide. This study is the
      first to report sexual offenses among children in Jordan. As such, it provides
      baseline data that can be used to inform policy and prevention strategies focused
      on reducing sexual violence among this vulnerable segment of the Jordanian
      population.

PMID- 26301440
TI  - Family Resilience Resources in Coping With Child Sexual Abuse in South Africa.
AB  - The aim of this qualitative study was to identify resources of family resilience
      that help families cope with child sexual abuse. Data were collected from a
      purposeful sample of parents representing nine poor families living in the
      Western Cape Province, South Africa. The narratives of the participants were
      analyzed thematically. The results indicate that the families, despite adverse
      situations, utilized internal and external resilience resources. Internal
      resources were the parents' relationship with their children, their own emotional
      functioning and attitudes, the children's ability to cope with the abuse,
      boundaries in the family, insight into their children's emotional needs, and
      sibling relationships. External family resources were the support of extended
      family members, friends, and a local community-based nonprofit organization
      working with child sexual abuse and schools. The empowering role of the
      identified resources for family resilience should be enhanced in interventions,
      while future studies could further explore these aspects in families confronted
      with child sexual abuse. 

PMID- 26301441
TI  - Training Mental Health Professionals in Child Sexual Abuse: Curricular
      Guidelines.
AB  - Given the incidence of child sexual abuse in the United States, mental health
      professionals need training to detect, assess, and treat victims and should
      possess a clear understanding of the process of victimization. However, many
      mental health professionals who work with children and families have not been
      exposed to any training in child sexual abuse during their formal education. This
      article will examine the need for such training, suggest critical components of
      child sexual abuse training, and describe various methods of training (e.g., in
      person, Web-based, and community resources). 

PMID- 26301442
TI  - Is Laughing at the Expense of Victims and Offenders a Red Flag? Humor and
      Secondary Traumatic Stress.
AB  - Those who work with human trauma often use humor to handle job stressors.
      Research has demonstrated that lighthearted humor is related to lower secondary
      traumatic stress scores, while gallows humor has the inverse relationship. This
      work explores how three types of humor relate to secondary traumatic stress: (a)
      humor at the expense of victims, (b) humor at the expense of offenders, and (c)
      humor containing sexual innuendo. Internet crimes against children taskforce
      personnel completed questionnaires about secondary traumatic stress and coping
      techniques. Humor at the expense of victims was rarely used, but when it was, it
      was indicative of higher secondary traumatic stress. There were no relationships
      between secondary traumatic stress and the use of humor at the expense of
      offenders or humor containing sexual innuendo. 

PMID- 26301445
TI  - The Alteration of Life History Traits and Increased Success of Halipegus
      eccentricus Through the Use of a Paratenic Host: A Comparative Study.
AB  - Complex life cycles are a hallmark characteristic of many parasites; however,
      little is known about the process by which life cycles become more complex
      through the addition of hosts. Paratenic hosts are present in the life cycles of
      several phylogenetically distinct groups of helminths; this suggests that they
      may play a key role during this process. This study examined the development of
      metacercariae of Halipegus eccentricus within intermediate microcrustacean and
      odonate paratenic hosts. Then a comparative approach was used to evaluate how
      life history traits of H. eccentricus within the anuran definitive hosts differ
      between metacercariae of the same age that developed within an intermediate
      ostracod host or a paratenic odonate host. The results of this study indicate
      that metacercariae of H. eccentricus do not grow at the same rate in different
      intermediate hosts, and significant differences exist in growth within
      intermediate and paratenic hosts. Individuals from odonate paratenic hosts always
      had larger bodies and suckers than those of metacercariae of the same age that
      develop within microcrustacean intermediate hosts. Furthermore, metacercariae
      from odonates were more successful in establishing and migrating in definitive
      anuran hosts. Last, individuals from paratenic hosts began reproducing earlier
      within anuran definitive hosts than age-matched worms that develop within the
      intermediate hosts. Collectively these results suggest that the variation in body
      and sucker sizes within odonate and microcrustacean hosts may carry over to the
      definitive host and in the case of H. eccentricus using the paratenic host
      increases transmission and alters other life history traits within definitive
      hosts. These results indicate that using a paratenic host can affect the success
      of parasites in subsequent hosts, and therefore these hosts may provide benefits
      other than just increasing transmission by bridging an ecological gap. 

PMID- 26301444
TI  - Cancer cell migration in 3D tissue: negotiating space by proteolysis and nuclear
      deformability.
AB  - Efficient tumor cell invasion into the surrounding desmoplastic stroma is a
      hallmark of cancer progression and involves the navigation through available
      small tissue spaces existent within the dense stromal network. Such navigation
      includes the reciprocal adaptation of the moving tumor cell, including the
      nucleus as largest and stiffest organelle, to pre-existent or de-novo generated
      extracellular matrix (ECM) gaps, pores and trails within stromal compartments.
      Within the context of migration, we briefly summarize physiological and tumor
      related changes in ECM geometries as well as tissue proteolysis. We then focus on
      mechanisms that ensure the successful translocation of a nucleus through a
      confining pore by cytoskeleton-mediated coupling, as well as regulators of cell
      and nuclear deformability such as chromatin organization and nuclear lamina
      expression. In summary, understanding dynamic nuclear mechanics during migration
      in response to confined space will add to a better conceptual appreciation of
      cancer invasion and progression. 

PMID- 26301446
TI  - English- and Mandarin-learning infants' discrimination of actions and objects in
      dynamic events.
AB  - The present studies examined the role of linguistic experience in directing
      English and Mandarin learners' attention to aspects of a visual scene.
      Specifically, they asked whether young language learners in these 2 cultures
      attend to differential aspects of a word-learning situation. Two groups of
      English and Mandarin learners, 6-8-month-olds (n = 65) and 17-19-month-olds (n =
      91), participated in 2 studies, based on a habituation paradigm, designed to test
      infants' discrimination between actions and objects in dynamic events. In Study
      1, these stimuli were presented in silence, whereas in Study 2, a verbal label
      accompanied videos. Results showed that 6-8-month-olds could discriminate action
      changes but not object changes, whereas 17-19-month-olds could discriminate both
      types of changes. However, there were only very subtle cross-linguistic
      differences in these patterns when the scenes were presented together with a
      verbal label. These findings show strong evidence for universal developmental
      trends in attention, with somewhat weaker evidence that the differences in the
      types of words Mandarin- versus English-learning children produce or are exposed
      to affect attention to different aspects of a scene in the first 2 years of life.

PMID- 26301447
TI  - Computational fluency and strategy choice predict individual and cross-national
      differences in complex arithmetic.
AB  - The present study tested the hypothesis that children's fluency with basic number
      facts and knowledge of computational strategies, derived from early arithmetic
      experience, predicts their performance on complex arithmetic problems. First
      grade students from United States and Taiwan (N = 152, mean age: 7.3 years) were
      presented with problems that differed in difficulty: single-, mixed-, and double
      digit addition. Children's strategy use varied as a function of problem
      difficulty, consistent with Siegler's theory of strategy choice. The use of
      decomposition strategy interacted with computational fluency in predicting the
      accuracy of double-digit addition. Further, the frequency of decomposition and
      computational fluency fully mediated cross-national differences in accuracy on
      these complex arithmetic problems. The results indicate the importance of both
      fluency with basic number facts and the decomposition strategy for later
      arithmetic performance.

PMID- 26301448
TI  - Iron homeostasis during risperidone treatment in children and adolescents.
AB  - OBJECTIVE: Previous cross-sectional evidence has linked antipsychotic-related
      weight gain to reduced body iron concentration. Using longitudinal data, we
      examined the association between changes in weight following risperidone
      initiation or discontinuation and ferritin concentration. METHOD: Study 1:
      Between April 2004 and September 2007, participants were enrolled from outpatient
      settings in a prospective randomized clinical trial comparing the efficacy of
      risperidone monotherapy to the combination of risperidone and behavior therapy in
      targeting disruptive behavior in 4- to 13-year-old children with DSM-IV-TR-based
      autism spectrum disorder. Study 2: Medically healthy 7- to 17-year-old
      participants in long-term open-label risperidone treatment at study entry
      returned for follow-up 1.5 years later, between July 2007 and July 2011.
      Available blood samples were used to measure ferritin. Linear multivariable
      regression analysis tested the association between ferritin concentration and
      change in age-sex-specific body mass index (BMI) z score between study entry and
      endpoint, adjusting for relevant confounders. RESULTS: Study 1 sample consisted
      of 73 participants (85% males, mean age: 7.7 +/- 2.4 years). After 18.0 +/- 2.0
      weeks on risperidone, their BMI z score increased by 0.93 +/- 0.70 points and
      ferritin concentration declined by 6.8 +/- 13.3 MUg/L. After adjusting for age
      and sex, change in BMI z score was inversely correlated with percent change in
      ferritin concentration (beta = -18.3, P < .003). Study 2 participants had all
      been receiving risperidone at study entry. At follow-up, 1.5 +/- 0.3 years later,
      risperidone was discontinued in 26 of the 96 who were included in the analysis.
      Neither change in BMI z score nor in ferritin concentration was different between
      those who continued versus discontinued risperidone. However, a reduction in BMI
      z score between study entry and follow-up was associated with higher ferritin
      concentration at follow-up in participants who discontinued risperidone compared
      to those who continued it (P = .01). CONCLUSIONS: Risperidone-related weight gain
      is associated with a reduction in body iron reserves, which appears to improve
      with weight loss following risperidone discontinuation. Preliminary evidence
      suggests that risperidone may also directly inhibit iron absorption. TRIAL
      REGISTRATION: ClinicalTrials.gov Identifier: NCT00080145.

PMID- 26301449
TI  - Rapid Phytotransformation of Benzotriazole Generates Synthetic Tryptophan and
      Auxin Analogs in Arabidopsis.
AB  - Benzotriazoles (BTs) are xenobiotic contaminants widely distributed in aquatic
      environments and of emerging concern due to their polarity, recalcitrance, and
      common use. During some water reclamation activities, such as stormwater
      bioretention or crop irrigation with recycled water, BTs come in contact with
      vegetation, presenting a potential exposure route to consumers. We discovered
      that BT in hydroponic systems was rapidly (approximately 1-log per day)
      assimilated by Arabidopsis plants and metabolized to novel BT metabolites
      structurally resembling tryptophan and auxin plant hormones; <1% remained as
      parent compound. Using LC-QTOF-MS untargeted metabolomics, we identified two
      major types of BT transformation products: glycosylation and incorporation into
      the tryptophan biosynthetic pathway. BT amino acid metabolites are structurally
      analogous to tryptophan and the storage forms of auxin plant hormones. Critical
      intermediates were synthesized (authenticated by (1)H/(13)C NMR) for product
      verification. In a multiple-exposure temporal mass balance, three major
      metabolites accounted for >60% of BT. Glycosylated BT was excreted by the plants
      into the hydroponic medium, a phenomenon not observed previously. The observed
      amino acid metabolites are likely formed when tryptophan biosynthetic enzymes
      substitute synthetic BT for native indolic molecules, generating potential
      phytohormone mimics. These results suggest that BT metabolism by plants could
      mask the presence of BT contamination in the environment. Furthermore, BT-derived
      metabolites are structurally related to plant auxin hormones and should be
      evaluated for undesirable biological effects. 

PMID- 26301450
TI  - Research on Positive Indicators for Teacher-Child Relationship in Children with
      Intellectual Disabilities.
AB  - Teacher-child relationships (TCRs) are important factors in socio-emotional
      development and academic and behavioural outcomes. In Japan, occupational
      therapists (OTs) work with teachers and children with intellectual disabilities
      (ID) in school environment considering TCRs. This study aimed to identify
      positive indicators in TCRs among children with ID. We conducted interviews with
      23 Japanese preschool teachers working with children with ID in child development
      support centres (CDSCs) and used the Delphi method to evaluate and select
      positive indicators. We obtained 49 positive indicators belonging to 15
      conceptual indicators related to TCRs. The indicators that reached a high degree
      of agreement and consensus seems to be related to more fundamental social
      interaction aspects. These indicators could be used to enhance collaboration
      between OTs and teachers in the school environment, including CDSCs. We could not
      examine differences of positive social aspects depending on diagnostic features.
      It will be important for future work to examine differences in positive social
      aspects among children with other diagnostic features. Our findings could
      contribute to the development of an assessment tool to evaluate positive aspects
      of teacher-child interactions and their progress.

PMID- 26301451
TI  - Neural stem/progenitor cell-laden microfibers promote transplant survival in a
      mouse transected spinal cord injury model.
AB  - Previous studies have demonstrated that transplantation of neural stem/progenitor
      cells (NS/PCs) into the lesioned spinal cord can promote functional recovery
      following incomplete spinal cord injury (SCI) in animal models. However, this
      strategy is insufficient following complete SCI because of the gap at the lesion
      epicenter. To obtain functional recovery in a mouse model of complete SCI, this
      study uses a novel collagen-based microfiber as a scaffold for engrafted NS/PCs.
      We hypothesized that the NS/PC-microfiber combination would facilitate lesion
      closure as well as transplant survival in the transected spinal cord. NS/PCs were
      seeded inside the novel microfibers, where they maintained their capacity to
      differentiate and proliferate. After transplantation, the stumps of the
      transected spinal cord were successfully bridged by the NS/PC-laden microfibers.
      Moreover, the transplanted cells migrated into the host spinal cord and
      differentiated into three neural lineages (astrocytes, neurons, and
      oligodendrocytes). However, the NS/PC-laden scaffold could not achieve a neural
      connection between the rostral end of the injury and the intact caudal area of
      the spinal cord, nor could it achieve recovery of motor function. To obtain
      optimal functional recovery, a microfiber design with a modified composition may
      be useful. Furthermore, combinatorial therapy with rehabilitation and/or
      medications should also be considered for practical success of biomaterial/cell
      transplantation-based approaches to regenerative medicine.

PMID- 26301453
TI  - Automated segmentation of wood fibres in micro-CT images of paper.
AB  - A novel algorithm has been developed and validated to isolate individual
      papermaking fibres in micro-computed tomographic images of paper handsheets as a
      first step to characterize the structure of the paper. The three-step fibre
      segmentation algorithm segments the papermaking fibres by (i) tracking the hollow
      inside the fibres via a modified connected component methodology, (ii) extracting
      the fibre walls using a distance transform and (iii) labelling the fibres through
      collapsed sections by a final refinement step. Furthermore, postprocessing
      algorithms have been developed to calculate the length and coarseness of the
      segmented fibres. The fibre segmentation algorithm is the first ever reported
      method for the automated segmentation of the tortuous three-dimensional
      morphology of papermaking fibres within microstructural images of paper
      handsheets. The method is not limited to papermaking fibres, but can be applied
      to any material consisting of tortuous and hollow fibres. 

PMID- 26301454
TI  - Thirty-Day Readmission Rates Among Dual-Eligible Beneficiaries.
AB  - PURPOSE: Dual-eligible beneficiaries represented 19% of Medicare and 14% of
      Medicaid enrollment in 2009. Of Medicare discharges among dually eligible
      beneficiaries, 21.5% resulted in a 30-day rehospitalization. Little has been
      published regarding dual-eligible beneficiaries' readmission rates and factors
      affecting readmission. METHODS: We conducted a cross-sectional analysis of
      Medicare claims, restricted to 297,084 beneficiaries with a hospitalization from
      February 1, 2009, through November 30, 2009. FINDINGS: Dual eligibles had higher
      hospitalization and 30-day readmission rates than Medicare-only beneficiaries.
      Multivariable regression indicated dual eligibility, younger age, and specific
      chronic conditions increased the likelihood of a 30-day readmission. Rural dually
      eligible beneficiaries had lower readmission rates than other beneficiaries, and
      they had a protective effect of physician follow-up care. CONCLUSIONS: Having a
      30-day physician follow-up had differential effects in urban versus rural
      locations, yet rural residents had a higher rate of follow-up care. The impact of
      adequate follow-up care, and how rural populations are successful, would be
      beneficial to understand. Substantial savings could accrue if interventions
      reduced readmissions among dual-eligible beneficiaries.

PMID- 26301452
TI  - Resolvins attenuate inflammation and promote resolution in cigarette smoke
      exposed human macrophages.
AB  - Inflammation is a protective response to injury, but it can become chronic,
      leading to tissue damage and disease. Cigarette smoke causes multiple
      inflammatory diseases, which account for thousands of deaths and cost billions of
      dollars annually. Cigarette smoke disrupts the function of immune cells, such as
      macrophages, by prolonging inflammatory signaling, promoting oxidative stress,
      and impairing phagocytosis, contributing to increased incidence of infections.
      Recently, new families of lipid-derived mediators, "specialized proresolving
      mediators" (SPMs), were identified. SPMs play a critical role in the active
      resolution of inflammation by counterregulating proinflammatory signaling and
      promoting resolution pathways. We have identified dysregulated concentrations of
      lipid mediators in exhaled breath condensate, bronchoalveolar lavage fluid, and
      serum from patients with chronic obstructive pulmonary disease (COPD). In human
      alveolar macrophages from COPD and non-COPD patients, D-series resolvins
      decreased inflammatory cytokines and enhanced phagocytosis. To further
      investigate the actions of resolvins on human cells, macrophages were
      differentiated from human blood monocytes and treated with D-series resolvins and
      then exposed to cigarette smoke extract. Resolvins significantly suppressed
      macrophage production of proinflammatory cytokines, enzymes, and lipid mediators.
      Resolvins also increased anti-inflammatory cytokines, promoted an M2 macrophage
      phenotype, and restored cigarette smoke-induced defects in phagocytosis,
      highlighting the proresolving functions of these molecules. These actions were
      receptor-dependent and involved modulation of canonical and noncanonical NF
      kappaB expression, with the first evidence for SPM action on alternative NF
      kappaB signaling. These data show that resolvins act on human macrophages to
      attenuate cigarette smoke-induced inflammatory effects through proresolving
      mechanisms and provide new evidence of the therapeutic potential of SPMs. 

PMID- 26301455
TI  - N-linked glycosylation of recombinant cellobiohydrolase I (Cel7A) from
      Penicillium verruculosum and its effect on the enzyme activity.
AB  - Cellobiohydrolase I from Penicillium verruculosum (PvCel7A) has four potential N
      glycosylation sites at its catalytic module: Asn45, Asn194, Asn388, and Asn430.
      In order to investigate how the N-glycosylation influences the activity and other
      properties of the enzyme, the wild type (wt) PvCel7A and its mutant forms,
      carrying Asn to Ala substitutions, were cloned into Penicillium canescens PCA10
      (niaD-) strain, a fungal host for production of heterologous proteins. The
      rPvCel7A-wt and N45A, N194A, N388A mutants were successfully expressed and
      purified for characterization, whereas the expression of N430A mutant was not
      achieved. The MALDI-TOF mass spectrometry fingerprinting of peptides, obtained as
      a result of digestion of rPvCel7A forms with specific proteases, showed that the
      N-linked glycans represent variable high-mannose oligosaccharides and the
      products of their sequential enzymatic trimming, according to the formula (Man)0
      13 (GlcNAc)2 , or a single GlcNAc residue. Mutations had no notable effect on pH
      optimum of PvCel7A activity and enzyme thermostability. However, the mutations
      influenced both the enzyme adsorption ability on Avicel and its activity against
      natural and synthetic substrates. In particular, the N45A mutation led to a
      significant increase in the rate of Avicel and milled aspen wood hydrolysis,
      while the substrate digestion rates in the case of N194A and N388A mutants were
      notably lower relative to rPvCel7A-wt. These data, together with data of 3D
      structural modeling of the PvCel7A catalytic module, indicate that the N-linked
      glycans are an important part of the processive catalytic machinery of PvCel7A.

PMID- 26301456
TI  - Clinical impact of selective and nonselective beta-blockers on survival in
      patients with ovarian cancer.
AB  - BACKGROUND: Preclinical evidence has suggested that sustained adrenergic
      activation can promote ovarian cancer growth and metastasis. The authors examined
      the impact of beta-adrenergic blockade on the clinical outcome of women with
      epithelial ovarian, primary peritoneal, or fallopian tube cancers (collectively,
      epithelial ovarian cancer [EOC]). METHODS: A multicenter review of 1425 women
      with histopathologically confirmed EOC was performed. Comparisons were made
      between patients with documented beta-blocker use during chemotherapy and those
      without beta-blocker use. RESULTS: The median age of patients in the current
      study was 63 years (range, 21-93 years). The sample included 269 patients who
      received beta-blockers. Of those, 193 (71.7%) were receiving beta-1-adrenergic
      receptor selective agents, and the remaining patients were receiving nonselective
      beta antagonists. The primary indication for beta-blocker use was hypertension
      but also included arrhythmia and postmyocardial infarction management. For
      patients receiving any beta-blocker, the median overall survival (OS) was 47.8
      months versus 42 months for nonusers (P =.04). The median OS based on beta
      blocker receptor selectivity was 94.9 months for those receiving nonselective
      beta-blockers versus 38 months for those receiving beta-1-adrenergic receptor
      selective agents (P<.001). Hypertension was associated with decreased OS compared
      with no hypertension across all groups. However, even among patients with
      hypertension, a longer median OS was observed among users of a nonselective beta
      blocker compared with nonusers (38.2 months vs 90 months; P<.001). CONCLUSIONS:
      Use of nonselective beta-blockers in patients with EOC was associated with longer
      OS. These findings may have implications for new therapeutic approaches. Cancer
      2015;121:3435-43. (c) 2015 American Cancer Society.

PMID- 26301457
TI  - The impact of prolapse mesh on vaginal smooth muscle structure and function.
AB  - OBJECTIVE: To evaluate the impact of prolapse meshes on vaginal smooth muscle
      structure (VaSM) and function, and to evaluate these outcomes in the context of
      the mechanical and textile properties of the mesh. DESIGN: Three months following
      the implantation of three polypropylene prolapse meshes with distinct textile and
      mechanical properties, mesh tissue explants were evaluated for smooth muscle
      contraction, innervation, receptor function, and innervation density. SETTING:
      Magee-Womens Research Institute at the University of Pittsburgh. POPULATION:
      Thirty-four parous rhesus macaques of similar age, parity, and pelvic organ
      prolapse quantification (POP-Q) scores. METHODS: Macaques were implanted with
      mesh via sacrocolpopexy. The impact of Gynemesh(TM)  PS (Ethicon; n = 7),
      Restorelle((r)) (Coloplast; n = 7), UltraPro(TM) parallel and UltraPro(TM)
      perpendicular (Ethicon; n = 6 and 7, respectively) were compared with sham
      operated controls (n = 7). Outcomes were analysed by Kruskal-Wallis ANOVA, Mann
      Whitney U-tests and multiple regression analysis (P < 0.05). MEAN OUTCOME
      MEASURES: Vaginal tissue explants were evaluated for the maximum contractile
      force generated following muscle, nerve, and receptor stimulation, and for
      peripheral nerve density. RESULTS: Muscle myofibre, nerve, and receptor-mediated
      contractions were negatively affected by mesh only in the grafted region (P <
      0.001, P = 0.002, and P = 0.008, respectively), whereas cholinergic and
      adrenergic nerve densities were affected in the grafted (P = 0.090 and P = 0.008,
      respectively) and non-grafted (P = 0.009 and P = 0.005, respectively) regions.
      The impact varied by mesh property, as mesh stiffness was a significant predictor
      of the negative affect on muscle function and nerve density (P < 0.001 and P =
      0.013, respectively), whereas mesh and weight was a predictor of receptor
      function (P < 0.001). CONCLUSIONS: Mesh has an overall negative impact on VaSM,
      and the effects are a function of mesh properties, most notably, mesh stiffness.
      TWEETABLE ABSTRACT: Prolapse mesh affects vaginal smooth muscle.

PMID- 26301458
TI  - Correcting heat-induced chemical shift distortions in proton resonance frequency
      shift thermometry.
AB  - PURPOSE: To reconstruct proton resonance frequency-shift temperature maps free of
      chemical shift distortions. THEORY AND METHODS: Tissue heating created by thermal
      therapies such as focused ultrasound surgery results in a change in proton
      resonance frequency that causes geometric distortions in the image and calculated
      temperature maps, in the same manner as other chemical shift and off-resonance
      distortions if left uncorrected. We propose an online-compatible algorithm to
      correct these distortions in 2DFT and echo-planar imaging acquisitions, which is
      based on a k-space signal model that accounts for proton resonance frequency
      change-induced phase shifts both up to and during the readout. The method was
      evaluated with simulations, gel phantoms, and in vivo temperature maps from
      brain, soft tissue tumor, and uterine fibroid focused ultrasound surgery
      treatments. RESULTS: Without chemical shift correction, peak temperature and
      thermal dose measurements were spatially offset by approximately 1 mm in vivo.
      Spatial shifts increased as readout bandwidth decreased, as shown by up to 4-fold
      greater temperature hot spot asymmetry in uncorrected temperature maps. In most
      cases, the computation times to correct maps at peak heat were less than 10 ms,
      without parallelization. CONCLUSION: Heat-induced proton resonance frequency
      changes create chemical shift distortions in temperature maps resulting from MR
      guided focused ultrasound surgery ablations, but the distortions can be corrected
      using an online-compatible algorithm. Magn Reson Med 76:172-182, 2016. (c) 2015
      Wiley Periodicals, Inc.

PMID- 26301459
TI  - Kidney function changes with aging in adults: comparison between cross-sectional
      and longitudinal data analyses in renal function assessment.
AB  - The study evaluated whether the renal function decline rate per year with age in
      adults varies based on two primary statistical analyses: cross-section (CS),
      using one observation per subject, and longitudinal (LT), using multiple
      observations per subject over time. A total of 16628 records (3946 subjects; age
      range 30-92 years) of creatinine clearance and relevant demographic data were
      used. On average, four samples per subject were collected for up to 2364 days
      (mean: 793 days). A simple linear regression and random coefficient models were
      selected for CS and LT analyses, respectively. The renal function decline rates
      per year were 1.33 and 0.95 ml/min/year for CS and LT analyses, respectively, and
      were slower when the repeated individual measurements were considered. The study
      confirms that rates are different based on statistical analyses, and that a
      statistically robust longitudinal model with a proper sampling design provides
      reliable individual as well as population estimates of the renal function decline
      rates per year with age in adults. In conclusion, our findings indicated that one
      should be cautious in interpreting the renal function decline rate with aging
      information because its estimation was highly dependent on the statistical
      analyses. From our analyses, a population longitudinal analysis (e.g. random
      coefficient model) is recommended if individualization is critical, such as a
      dose adjustment based on renal function during a chronic therapy.

PMID- 26301460
TI  - Imidazolium Sulfonates as Environmental-Friendly Catalytic Systems for the
      Synthesis of Biologically Active 2-Amino-4H-chromenes: Mechanistic Insights.
AB  - Ionic Liquids (ILs) are valuable reaction media extremely useful in industrial
      sustainable organic synthesis. We describe here the study on the multicomponent
      reaction (MCR) between salicylaldehyde (2) and ethyl cyanoacetate (3), catalyzed
      by imidazolium sulfonates, to form chromenes 1, a class of heterocyclic scaffolds
      exhibiting relevant biological activity. We have clarified the reaction mechanism
      by combining the experimental results with computational studies. The results
      reported herein suggest that both the imidazolium core and the sulfonate anions
      in the selected ILs are involved in the reaction course acting as hydrogen bond
      donors and acceptors, respectively. Contrarily to the most widely accepted
      mechanism through initial Knoevenagel condensation, the most favorable reaction
      pathway consists of an aldolic reaction between reagents followed by
      heterocyclization, subsequent dehydration, and, finally, the Michael addition of
      the second molecule of ethyl cyanoacetate (3) to yield the chromenes 1. 

PMID- 26301461
TI  - An Integrative Analysis of Foot-and-Mouth Disease Virus Carriers in Vietnam
      Achieved Through Targeted Surveillance and Molecular Epidemiology.
AB  - Foot-and-mouth disease (FMD) is a major constraint to transboundary trade in
      animal products, yet much of its natural ecology and epidemiology in endemic
      regions is still poorly understood. To address this gap, a multidisciplinary,
      molecular and conventional epidemiological approach was applied to an
      investigation of endemic FMD in Vietnam. Within the study space, it was found
      that 22.3% of sampled ruminants had previously been infected with FMD virus
      (FMDV), of which 10.8% were persistent, asymptomatic carriers (2.4% of the total
      population). Descriptive data collected from targeted surveillance and a farm
      questionnaire showed a significantly lower prevalence of FMDV infection for dairy
      farms. In contrast, farms of intermediate size and/or history of infection in
      2010 were at increased risk of FMD exposure. At the individual animal level,
      buffalo had the highest exposure risk (over cattle), and there was spatial
      heterogeneity in exposure risk at the commune level. Conversely, carrier
      prevalence was higher for beef cattle, suggesting lower susceptibility of buffalo
      to persistent FMDV infection. To characterize virus strains currently circulating
      in Vietnam, partial FMDV genomic (VP1) sequences from carrier animals collected
      between 2012 and 2013 (N = 27) and from FMDV outbreaks between 2009 and 2013 (N =
      79) were compared by phylogenetic analysis. Sequence analysis suggested that
      within the study period, there were two apparent novel introductions of serotype
      A viruses and that the dominant lineage of serotype O in Vietnam shifted from
      SEA/Mya-98 to ME-SA/PanAsia. FMDV strains shared close ancestors with FMDV from
      other South-East Asian countries indicating substantial transboundary movement of
      the predominant circulating strains. Close genetic relationships were observed
      between carrier and outbreak viruses, which may suggest that asymptomatic
      carriers of FMDV contribute to regional disease persistence. Multiple viral
      sequences obtained from carrier cattle over a 1-year period had considerable
      within-animal genetic variation, indicating within-host virus evolution.

PMID- 26301463
TI  - Materialism.
AB  - Materialism is nearly universally assumed by cognitive scientists. Intuitively,
      materialism says that a person's mental states are nothing over and above his or
      her material states, while dualism denies this. Philosophers have introduced
      concepts (e.g., realization and supervenience) to assist in formulating the
      theses of materialism and dualism with more precision, and distinguished among
      importantly different versions of each view (e.g., eliminative materialism,
      substance dualism, and emergentism). They have also clarified the logic of
      arguments that use empirical findings to support materialism. Finally, they have
      devised various objections to materialism, objections that therefore serve also
      as arguments for dualism. These objections typically center around two features
      of mental states that materialism has had trouble in accommodating. The first
      feature is intentionality, the property of representing, or being about, objects,
      properties, and states of affairs external to the mental states. The second
      feature is phenomenal consciousness, the property possessed by many mental states
      of there being something it is like for the subject of the mental state to be in
      that mental state. WIREs Cogn Sci 2012, 3:281-292. doi: 10.1002/wcs.1174 For
      further resources related to this article, please visit the WIREs website. 

PMID- 26301462
TI  - Pharmacological Evidence that Histamine H3 Receptors Mediate Histamine-Induced
      Inhibition of the Vagal Bradycardic Out-flow in Pithed Rats.
AB  - In vivo stimulation of cardiac vagal neurons induces bradycardia by acetylcholine
      (ACh) release. As vagal release of ACh may be modulated by autoreceptors
      (muscarinic M2 ) and heteroreceptors (including serotonin 5-HT1 ), this study has
      analysed the pharmacological profile of the receptors involved in histamine
      induced inhibition of the vagal bradycardic out-flow in pithed rats. For this
      purpose, 180 male Wistar rats were pithed, artificially ventilated and pre
      treated (i.v.) with 1 mg/kg atenolol, followed by i.v. administration of
      physiological saline (1 ml/kg), histamine (10, 50, 100 and 200 MUg/kg) or the
      selective histamine H1 (2-pyridylethylamine), H2 (dimaprit), H3 (methimepip) and
      H4 (VUF 8430) receptor agonists (1, 10, 50 and 100 MUg/kg each). Under these
      conditions, electrical stimulation (3, 6 and 9 Hz; 15 +/- 3 V and 1 ms) of the
      vagus nerve resulted in frequency-dependent bradycardic responses, which were (i)
      unchanged during the infusions of saline, 2-pyridylethylamine, dimaprit or VUF
      8430; and (ii) dose-dependently inhibited by histamine or methimepip. Moreover,
      the inhibition of the bradycardia caused by 50 MUg/kg of either histamine or
      methimepip (which failed to inhibit the bradycardic responses to i.v. bolus
      injections of acetylcholine; 1-10 MUg/kg) was abolished by the H3 receptor
      antagonist JNJ 10181457 (1 mg/kg, i.v.). In conclusion, our results suggest that
      histamine-induced inhibition of the vagal bradycardic out-flow in pithed rats is
      mainly mediated by pre-junctional activation of histamine H3 receptors, as
      previously demonstrated for the vasopressor sympathetic out-flow and the
      vasodepressor sensory CGRPergic (calcitonin gene-related peptide) out-flow. 

PMID- 26301464
TI  - Levels of analysis: philosophical issues.
AB  - A focal concern in the philosophy of cognitive science is whether the world is
      fundamentally organized into hierarchies of levels and whether mental phenomena
      exemplify such higher-level regularities and hence are unexplainable by lower
      level theory. Levels of analysis represent different stances from which
      predictive and explanatory theories are constructed, and each level of analysis
      contains a set of kind terms representing things in nature, predicates
      representing properties or relations, and law-like generalizations or principles.
      The concept of levels of analysis, which plays a central role in debates over the
      cognitive architecture of the mind in cognitive science, is concerned mainly with
      the choice of which level of analysis can be expected to maximize the
      predictability and explanatory power of cognitive modeling. The core
      philosophical issues concerning the levels of analysis are the problem of
      theoretical reduction between the levels, the concept of supervenience, the
      problem of emergent properties, and the conceptual coherence of the notion of
      downward causation. WIREs Cogn Sci 2012, 3:315-325. doi: 10.1002/wcs.1179 For
      further resources related to this article, please visit the WIREs website. 

PMID- 26301465
TI  - The development of causal reasoning.
AB  - How do inference rules for causal learning themselves change developmentally? A
      model of the development of causal reasoning must address this question, as well
      as specify the inference rules. Here, the evidence for developmental changes in
      processes of causal reasoning is reviewed, with the distinction made between
      diagnostic causal inference and causal prediction. Also addressed is the paradox
      of a causal reasoning literature that highlights the competencies of young
      children and the proneness to error among adults. WIREs Cogn Sci 2012, 3:327-335.
      doi: 10.1002/wcs.1160 For further resources related to this article, please visit
      the WIREs website. 

PMID- 26301466
TI  - Functionalism as a philosophical theory of the cognitive sciences.
AB  - Functionalism is a philosophical theory (or family of theories) concerning the
      nature of mental states. According to functionalism psychological/cognitive
      states are essentially functional states of whole systems. Functionalism
      characterizes psychological states essentially according to what they do, by
      their relations to stimulus inputs and behavioral outputs as well as their
      relations to other psychological and nonpsychological internal states of a
      system. The central constructive relation for functionalism is the so-called
      realization relation. Realization is a proposal for how psychological states can
      be real, physical, and causally efficacious while at the same time preserving the
      autonomy of cognitive explanations and avoiding reduction or elimination. WIREs
      Cogn Sci 2012, 3:337-348. doi: 10.1002/wcs.1170 For further resources related to
      this article, please visit the WIREs website. 

PMID- 26301467
TI  - Development of spatial cognition.
AB  - Spatial cognition plays an essential role in everyday functioning and provides a
      foundation for successful performance in scientific and technological fields.
      Reasoning about space involves processing information about distance, angles, and
      direction. Starting from infancy, children display sensitivity to these spatial
      properties, although their initial skills are quite limited. Subsequent
      development during early childhood and through the elementary school years
      involves gradual improvement in the use of individual frames of reference (i.e.,
      egocentric and allocentric), as well as in the ability to flexibly combine
      different types of spatial information. Similarly, there is a relatively long
      progression from the starting points, when infants and young children display
      sensitivity to distance and form simple spatial categories, to more mature
      spatial competence when older children and adults integrate distance and
      categorical information hierarchically. Such developments are associated with
      both the maturation of specific brain regions and accumulating experience,
      including interactions with the physical world and the acquisition of cultural
      tools. In particular, the mastery of symbolic spatial representations, such as
      maps and models, significantly augments basic spatial capabilities. While growing
      evidence implicates both biological and experiential factors in the development
      of spatial cognition, a deeper understanding of the mechanisms that underlie the
      developmental process requires further investigation of how such factors interact
      to produce organisms that function competently in their environments. WIREs Cogn
      Sci 2012, 3:349-362. doi: 10.1002/wcs.1171 For further resources related to this
      article, please visit the WIREs website. 

PMID- 26301468
TI  - Automaticity and multiple memory systems.
AB  - A large number of criteria have been proposed for determining when a behavior has
      become automatic. Almost all of these were developed before the widespread
      acceptance of multiple memory systems. Consequently, popular frameworks for
      studying automaticity often neglect qualitative differences in how different
      memory systems guide initial learning. Unfortunately, evidence suggests that
      automaticity criteria derived from these frameworks consistently misclassify
      certain sets of initial behaviors as automatic. Specifically, criteria derived
      from cognitive science mislabel much behavior still under the control of
      procedural memory as automatic, and criteria derived from animal learning
      mislabel some behaviors under the control of declarative memory as automatic.
      Even so, neither set of criteria make the opposite error-that is, both sets
      correctly identify any automatic behavior as automatic. In fact, evidence
      suggests that although there are multiple memory systems and therefore multiple
      routes to automaticity, there might nevertheless be only one common
      representation for automatic behaviors. A number of possible cognitive and
      cognitive neuroscience models of this single automaticity system are reviewed.
      WIREs Cogn Sci 2012, 3:363-376. doi: 10.1002/wcs.1172 For further resources
      related to this article, please visit the WIREs website. 

PMID- 26301469
TI  - Socioeconomic status and cognitive functioning: moving from correlation to
      causation.
AB  - A growing body of cognitive research uses sophisticated behavioral and
      neuroimaging measurements to demonstrate associations between family
      socioeconomic status (SES) and specific cognitive functions. We argue for the
      value in these kinds of studies of increased sophistication in the measurement
      and modeling of SES. With regard to measurement, SES combines several components,
      each of which represents distinct resources that might benefit children's
      cognitive development in different ways. Policy implications of studies using
      omnibus SES composites are problematic because there are no 'treatments' for
      enhancing overall SES, although policies abound for enhancing specific components
      of SES such as family income. Past literature offers guidance regarding how best
      to measure each of the SES components. With regard to modeling, we point out that
      the manipulability of economic, educational, and occupational components of SES
      varies, which provides opportunities for generating experimental or quasi
      experimental variation in some components but not others. Evidence on the causal
      connections between SES components and child outcomes is summarized. Both
      experimental and quasi-experimental studies involving manipulation of family
      income have demonstrated consistent associations with a number of cognitive
      measures. Quasi-experimental increases in maternal education have also shown
      associations with child achievement. We end with a discussion of useful
      directions in SES-related cognitive research. WIREs Cogn Sci 2012, 3:377-386.
      doi: 10.1002/wcs.1176 For further resources related to this article, please visit
      the WIREs website. 

PMID- 26301470
TI  - Models of spoken-word recognition.
AB  - All words of the languages we know are stored in the mental lexicon.
      Psycholinguistic models describe in which format lexical knowledge is stored and
      how it is accessed when needed for language use. The present article summarizes
      key findings in spoken-word recognition by humans and describes how models of
      spoken-word recognition account for them. Although current models of spoken-word
      recognition differ considerably in the details of implementation, there is
      general consensus among them on at least three aspects: multiple word candidates
      are activated in parallel as a word is being heard, activation of word candidates
      varies with the degree of match between the speech signal and stored lexical
      representations, and activated candidate words compete for recognition. No
      consensus has been reached on other aspects such as the flow of information
      between different processing levels, and the format of stored prelexical and
      lexical representations. WIREs Cogn Sci 2012, 3:387-401. doi: 10.1002/wcs.1178
      For further resources related to this article, please visit the WIREs website. 

PMID- 26301471
TI  - Ellipsis: computation of.
AB  - A computational account of ellipsis should specify not only how the meaning of an
      elliptical sentence is computed in context but also a description of what is
      being computed. Many proposals can be divided into two groups, as per whether
      they compute the meaning of an elliptical sentence based on the semantic or the
      syntactic parts of its context. A unifying theme of these proposals is that they
      are all based on the idea that the meaning of an elliptical sentence is
      determinable based on a structured representation which is transformationally
      related to its surface syntactic structure. WIREs Cogn Sci 2012, 3:411-418. doi:
      10.1002/wcs.1168 For further resources related to this article, please visit the
      WIREs website. 

PMID- 26301472
TI  - Self-control: limited resources and extensive benefits.
AB  - Successful self-control has many benefits for individuals and society as a whole.
      Self-regulation relies on a limited resource. After one act of self-control, this
      resource is reduced, thereby impairing future acts of self-control. Self-control
      resources can be managed and conserved for future tasks. Recent research on
      perceived self-control (in the self and others), self-control in interpersonal
      interactions, and the physiological basis of the limited resource model point to
      promising areas for future self-control research. WIREs Cogn Sci 2012, 3:419-423.
      doi: 10.1002/wcs.1173 For further resources related to this article, please visit
      the WIREs website. 

PMID- 26301475
TI  - Statin Use in Very Elderly Individuals, 1999-2012.

PMID- 26301474
TI  - Intravenous Artesunate for the Treatment of Severe and Complicated Malaria in the
      United States: Clinical Use Under an Investigational New Drug Protocol.
AB  - BACKGROUND: Quinidine gluconate, the only U.S. Food and Drug Administration
      approved treatment for life-threatening malaria in the United States, has a
      problematic safety profile and is often unavailable in hospitals. OBJECTIVE: To
      assess the safety and clinical benefit of intravenous artesunate as an
      alternative to quinidine. DESIGN: Retrospective case series. SETTING: U.S.
      hospitals. PATIENTS: 102 patients aged 1 to 72 years (90% adults; 61% men) with
      severe and complicated malaria. Patients received 4 weight-based doses of
      intravenous artesunate (2.4 mg/kg) under a treatment protocol implemented by the
      Centers for Disease Control and Prevention between January 2007 and December
      2010. At baseline, 35% had evidence of cerebral malaria, and 17% had severe
      hepatic impairment. Eligibility required the presence of microscopically
      confirmed malaria, need for intravenous treatment, and an impediment to
      quinidine. MEASUREMENTS: Clinical and laboratory data from each patient's
      hospital records were abstracted retrospectively, including information from
      baseline through a maximum 7-day follow-up, and presented before a physician
      committee to evaluate safety and clinical benefit outcomes. RESULTS: 7 patients
      died (mortality rate, 6.9%). The most frequent adverse events were anemia (65%)
      and elevated hepatic enzyme levels (49%). All deaths and most adverse events were
      attributed to the severity of malaria. Patients' symptoms generally improved or
      resolved within 3 days, and the median time to discharge from the intensive care
      unit was 4 days, even for patients with severe liver disease or cerebral malaria.
      More than 100 concomitant medications were used, with no documented drug-drug
      interactions. LIMITATION: Potential late-presenting safety issues might occur
      outside the 7-day follow-up. CONCLUSION: Artesunate was a safe and clinically
      beneficial alternative to quinidine.

PMID- 26301476
TI  - Global change pressures on soils from land use and management.
AB  - Soils are subject to varying degrees of direct or indirect human disturbance,
      constituting a major global change driver. Factoring out natural from direct and
      indirect human influence is not always straightforward, but some human activities
      have clear impacts. These include land-use change, land management and land
      degradation (erosion, compaction, sealing and salinization). The intensity of
      land use also exerts a great impact on soils, and soils are also subject to
      indirect impacts arising from human activity, such as acid deposition (sulphur
      and nitrogen) and heavy metal pollution. In this critical review, we report the
      state-of-the-art understanding of these global change pressures on soils,
      identify knowledge gaps and research challenges and highlight actions and
      policies to minimize adverse environmental impacts arising from these global
      change drivers. Soils are central to considerations of what constitutes
      sustainable intensification. Therefore, ensuring that vulnerable and high
      environmental value soils are considered when protecting important habitats and
      ecosystems, will help to reduce the pressure on land from global change drivers.
      To ensure that soils are protected as part of wider environmental efforts, a
      global soil resilience programme should be considered, to monitor, recover or
      sustain soil fertility and function, and to enhance the ecosystem services
      provided by soils. Soils cannot, and should not, be considered in isolation of
      the ecosystems that they underpin and vice versa. The role of soils in supporting
      ecosystems and natural capital needs greater recognition. The lasting legacy of
      the International Year of Soils in 2015 should be to put soils at the centre of
      policy supporting environmental protection and sustainable development. 

PMID- 26301477
TI  - Optimising screening for cognitive dysfunction in bipolar disorder: Validation
      and evaluation of objective and subjective tools.
AB  - INTRODUCTION: Cognitive impairment is common in bipolar disorder and contributes
      to socio-occupational difficulties. The objective was to validate and evaluate
      instruments to screen for and monitor cognitive impairments, and improve the
      understanding of the association between cognitive measures and socio
      occupational capacity. METHODS: Patients with bipolar disorder in partial or full
      remission (n=84) and healthy controls (n=68) were assessed with the Screen for
      Cognitive Impairment in Psychiatry (SCIP), Cognitive Complaints in Bipolar
      Disorder Rating Scale (COBRA), and established neuropsychological tests and
      subjective rating scales. Socio-occupational function and affective symptoms were
      evaluated with the Functional Assessment Short Test, and the Hamilton Depression
      Rating Scale 17-items and Young Mania Rating Scale, respectively. Concurrent
      validity of the SCIP and COBRA were assessed by correlation with established
      objective and subjective cognitive measures, and decision validity was determined
      with Receiver-Operating-Characteristic analyses. Correlations and linear
      regression analyses were conducted to determine the associations between
      objective and subjective cognitive impairment, and socio-occupational
      difficulties. RESULTS: The SCIP and COBRA correlated strongly with established
      objective and subjective cognitive measures, respectively. The SCIP yielded
      higher sensitivity and specificity for detection of cognitive dysfunction than
      the COBRA or a combined SCIP-COBRA measure. Correlations between objective and
      subjective cognitive impairment were weak but both were associated with socio
      occupational difficulties. LIMITATIONS: Influence of ageing was not investigated.
      CONCLUSIONS: The SCIP and COBRA are valid for detection of objective and
      subjective cognitive impairment in bipolar disorder. Screening for cognitive
      dysfunction should be conducted with an objective measure like the SCIP.

PMID- 26301479
TI  - At-line coupling of LC-MS to bioaffinity and selectivity assessment for metabolic
      profiling of ligands towards chemokine receptors CXCR1 and CXCR2.
AB  - This study describes an analytical method for bioaffinity and selectivity
      assessment of CXCR2 antagonists and their metabolites. The method is based on
      liquid chromatographic separation (LC) of metabolic mixtures followed by parallel
      mass spectrometry (MS) identification and bioaffinity determination. The
      bioaffinity is assessed using radioligand binding assays in 96-well plates after
      at-line nanofractionation. The described method was optimized for chemokines and
      low-molecular weight CXCR2 ligands. The limits of detection (LODs; injected
      amounts) for MK-7123, a high affinity binder to both CXCR1 and CXCR2 receptors
      belonging to the diaminocyclobutendione chemical class, were 40pmol in CXCR1
      binding and 8pmol in CXCR2 binding. For CXCL8, the LOD was 5pmol in both binding
      assays. A control compound was always taken along with each bioassay plate as
      triplicate dose-response curve. For MK-7123, the calculated IC50 values were
      314+/-59nM (CXCR1 binding) and 38+/-11nM (CXCR2 binding). For CXCL8, the IC50
      values were 6.9+/-1.4nM (CXCR1 binding) and 2.7+/-1.3nM (CXCR2 binding). After
      optimization, the method was applied to the analysis of metabolic mixtures of
      eight LMW CXCR2 antagonists generated by incubation with pig liver microsomes.
      Moreover, metabolic profiling of the MK-7123 compound was described using the
      developed method. Three bioactive metabolites were found, two of which were
      (partially) identified. This method is suitable for bioaffinity and selectivity
      assessment of mixtures targeting the CXCR2. In contrary to conventional LC-MS
      based metabolic profiling studies done at the early lead discovery stage,
      additional qualitative bioactivity information of drug metabolites is obtained
      with the method described. 

PMID- 26301478
TI  - Associations of maternal and paternal antenatal mood with offspring anxiety
      disorder at age 18 years.
AB  - OBJECTIVE: Maternal antenatal depression and anxiety are associated with
      increased risk of childhood behavioural and emotional problems in offspring; it
      remains unclear to what extent this is due to a maternal biological impact on
      foetal development. Here, we compare associations between maternal and paternal
      antenatal depression and anxiety with offspring anxiety disorders, thus
      controlling for some genetic and shared environmental factors. METHODS: We used
      data from the ALSPAC population cohort including measures of antenatal parental
      depression and anxiety. At 18 years, offspring completed the CIS-R interview,
      yielding diagnoses for anxiety disorders. Results were adjusted for confounding
      variables including parental postnatal depression and anxiety. RESULTS: Children
      of women with antenatal depression (18 weeks gestation), had an increased risk of
      anxiety disorders at 18 years of age (11.1% vs. 6.2%; adj. OR 1.75 (1.19, 2.58);
      p=0.01). Children of women with antenatal anxiety had increased risk of co-morbid
      anxiety and depression (adj. OR 1.39 (1.06, 1.82); p=0.02). No such associations
      were found with paternal antenatal depression or anxiety. LIMITATIONS: There was
      a high attrition rate from the original cohort to the CIS-R completion at 18
      years postpartum. Parental mood was only assessed together at one time point
      during the antenatal period. CONCLUSIONS: The differences in the association
      between maternal and paternal mood during pregnancy and child outcomes supports
      the hypothesis that foetal programming may account, at least in part, for this
      association. We highlight the potential opportunity for preventative intervention
      by optimising antenatal mental health.

PMID- 26301480
TI  - Hormone-like peptides in the venoms of marine cone snails.
AB  - The venoms of cone snails (genus Conus) are remarkably complex, consisting of
      hundreds of typically short, disulfide-rich peptides termed conotoxins. These
      peptides have diverse pharmacological targets, with injection of venom eliciting
      a range of physiological responses, including sedation, paralysis and sensory
      overload. Most conotoxins target the prey's nervous system but evidence of venom
      peptides targeting neuroendocrine processes is emerging. Examples include
      vasopressin, RFamide neuropeptides and recently also insulin. To investigate the
      diversity of hormone/neuropeptide-like molecules in the venoms of cone snails we
      systematically mined the venom gland transcriptomes of several cone snail species
      and examined secreted venom peptides in dissected and injected venom of the
      Australian cone snail Conus victoriae. Using this approach we identified several
      novel hormone/neuropeptide-like toxins, including peptides similar to the bee
      brain hormone prohormone-4, the mollusc ganglia neuropeptide elevenin, and
      thyrostimulin, a member of the glycoprotein hormone family, and confirmed the
      presence of insulin. We confirmed that at least two of these peptides are not
      only expressed in the venom gland but also form part of the injected venom
      cocktail, unambiguously demonstrating their role in envenomation. Our findings
      suggest that hormone/neuropeptide-like toxins are a diverse and integral part of
      the complex envenomation strategy of Conus. Exploration of this group of venom
      components offers an exciting new avenue for the discovery of novel
      pharmacological tools and drug candidates, complementary to conotoxins.

PMID- 26301481
TI  - Interplay between the hinge region of iron sulphur protein and the Qo site in the
      bc1 complex - Analysis of Plasmodium-like mutations in the yeast enzyme.
AB  - The respiratory chain bc1 complex is central to mitochondrial bioenergetics and
      the target of antiprotozoals. We characterized a modified yeast bc1 complex that
      more closely resemble Plasmodium falciparum enzyme. The mutant version was
      generated by replacing ten cytochrome b Qo site residues by P. falciparum
      equivalents. The Plasmodium-like changes caused a major dysfunction of the
      catalytic mechanism of the bc1 complex resulting in superoxide overproduction and
      respiratory growth defect. The defect was corrected by substitution of the
      conserved residue Y279 by a phenylalanine, or by mutations in or in the vicinity
      of the hinge domain of the iron-sulphur protein. It thus appears that side
      reactions can be prevented by the substitution Y279F or the modification of the
      iron-sulphur protein hinge region. Interestingly, P. falciparum - and all the
      apicomplexan - contains an unusual hinge region. We replaced the yeast hinge
      region by the Plasmodium version and combined it with the Plasmodium-like version
      of the Qo site. This combination restored the respiratory growth competence. It
      could be suggested that, in the apicomplexan, the hinge region and the cytochrome
      b Qo site have co-evolved to maintain catalytic efficiency of the bc1 complex Qo
      site. 

PMID- 26301483
TI  - Cumulative exposure to childhood stressors and subsequent psychological distress.
      An analysis of US panel data.
AB  - Research has shown that childhood stress increases the risk of poor mental health
      later in life. We examined the effect of childhood stressors on psychological
      distress and self-reported depression in young adulthood. Data were obtained from
      the Child Development Supplement (CDS) to the national Panel Study of Income
      Dynamics (PSID), a survey of US families that incorporates data from parents and
      their children. In 2005 and 2007, the Panel Study of Income Dynamics was
      supplemented with two waves of Transition into Adulthood (TA) data drawn from a
      national sample of young adults, 18-23 years old. This study included data from
      participants in the CDS and the TA (n = 2128), children aged 4-13 at baseline.
      Data on current psychological distress was used as an outcome variable in
      logistic regressions, calculated as odds ratios (OR) with 95% confidence
      intervals (CI). Latent Class Analyses were used to identify clusters based on the
      different childhood stressors. Associations were observed between cumulative
      exposure to childhood stressors and both psychological distress and self-reported
      depression. Individuals being exposed to three or more stressors had the highest
      risk (crude OR for psychological distress: 2.49 (95% CI: 1.16-5.33), crude OR for
      self-reported depression: 2.07 (95% CI: 1.15-3.71). However, a large part was
      explained by adolescent depressive symptoms. Findings support the long-term
      negative impact of cumulative exposure to childhood stress on psychological
      distress. The important role of adolescent depression in this association also
      needs to be taken into consideration in future studies. 

PMID- 26301485
TI  - A longitudinal examination of maternal, family, and area-level experiences of
      racism on children's socioemotional development: Patterns and possible
      explanations.
AB  - The association between experienced racial discrimination and poor health is now
      well documented, particularly among adult populations. However, longitudinal
      studies of the association between racism and child health are limited, and
      evidence on how racial discrimination experienced by members of children's
      immediate environment impact on child development, and the mechanisms by which
      this occurs, is scarce. We examined the longitudinal association between
      maternal, family, and area-level experiences of racial discrimination, and
      children's socioemotional development. We proposed that exposure to racial
      discrimination would be detrimental to children's socioemotional development via
      two mother-centred stress pathways: a worsening in maternal mental health, and an
      increase in harsh parenting practices. Data on ethnic minority mothers and their
      children were drawn from waves 3 to 5 (2006-2012) of the UK Millennium Cohort
      Study. Results of longitudinal path analyses show a strong association between
      maternal and family experiences of racial discrimination in wave 3, and a
      worsening in mother's mental health in wave 4. Maternal and family experiences of
      racial discrimination at wave 3 had an indirect effect on children's
      socioemotional development at wave 5. This occurred mainly via a worsening in
      mother's mental health, although some events of racial discrimination experienced
      by the mother and other family members also impacted negatively on children's
      socioemotional development via an increase in harsh parenting practices. We found
      a direct effect of maternal and family experiences of racial discrimination on
      children's socioemotional development. Our findings document the harm of growing
      up in a racist environment on the socioemotional development of children, and
      provide some evidence for the role of mother-centred stress mechanisms in linking
      vicarious exposure to racial discrimination to children's socioemotional
      development. 

PMID- 26301484
TI  - Anticipated regret to increase uptake of colorectal cancer screening (ARTICS): A
      randomised controlled trial.
AB  - Screening is important for early detection of colorectal cancer. Our aim was to
      determine whether a simple anticipated regret (AR) intervention could increase
      uptake of colorectal cancer screening. A randomised controlled trial of a simple,
      questionnaire-based AR intervention, delivered alongside existing pre
      notification letters, was conducted. A total of 60,000 adults aged 50-74 years
      from the Scottish National Screening programme were randomised into the following
      groups: (1) no questionnaire (control), (2) Health Locus of Control questionnaire
      (HLOC) or (3) HLOC plus AR questionnaire. The primary outcome was return of the
      guaiac faecal occult blood test (FOBT). The secondary outcomes included intention
      to return test kit and perceived disgust (ICK). A total of 59,366 people were
      analysed as allocated (intention-to-treat (ITT)); no overall differences were
      seen between the treatment groups on FOBT uptake (control: 57.3%, HLOC: 56.9%,
      AR: 57.4%). In total, 13,645 (34.2%) individuals returned the questionnaires.
      Analysis of the secondary questionnaire measures showed that AR indirectly
      affected FOBT uptake via intention, whilst ICK directly affected FOBT uptake over
      and above intention. The effect of AR on FOBT uptake was also moderated by
      intention strength: for less-than-strong intenders only, uptake was 4.2% higher
      in the AR (84.6%) versus the HLOC group (80.4%) (95% CI for difference (2.0,
      6.5)). The findings show that psychological concepts including AR and perceived
      disgust (ICK) are important factors in determining FOBT uptake. However, the AR
      intervention had no simple effect in the ITT analysis. It can be concluded that,
      in those with low intentions, exposure to AR may be required to increase FOBT
      uptake. The current controlled trials are presented at the website www.controlled
      trials.com (number: ISRCTN74986452). 

PMID- 26301486
TI  - Does the hand that controls the cigarette packet rule the smoker? Findings from
      ethnographic interviews with smokers in Canada, Australia, the United Kingdom and
      the USA.
AB  - Throughout the twentieth century, packaging was a carefully cultivated element of
      the appeal of the cigarette. However, the tobacco industry's control over
      cigarette packaging has been steadily eroded through legislation that aims to
      rebrand the packet from a desirable to a dangerous commodity-epitomized in
      Australia's introduction of plain packaging in 2012. Evident in both the
      enactment of cigarette packaging legislation and industry efforts to overturn it
      is the assumption that packets do things-i.e. that they have a critical role to
      play in either promoting or discouraging the habit. Drawing on 175 ethnographic
      interviews conducted with people smoking in public spaces in Vancouver, Canada;
      Canberra, Australia; Liverpool, England; and San Francisco, USA, we produce a
      'thick description' of smokers' engagements with cigarette packets. We illustrate
      that despite the very different types of cigarette packaging legislation in place
      in the four countries, there are marked similarities in the ways smokers engage
      with their packets. In particular, they are not treated as a purely visual sign;
      instead, a primary means through which one's own cigarette packet is apprehended
      is by touch rather than by sight. Smokers perceive cigarette packets largely
      through the operations of their hands-through their 'handiness'. Thus, our study
      findings problematize the assumption that how smokers engage with packets when
      asked to do so on a purely intellectual or aesthetic level reflects how they
      engage with packets as they are enfolded into their everyday lives. 

PMID- 26301487
TI  - Directed Metalation-Suzuki-Miyaura Cross-Coupling Strategies: Regioselective
      Synthesis of Hydroxylated 1-Methyl-phenanthrenes.
AB  - A general, efficient, and regioselective synthesis of a series of hydroxylated 1
      methylphenanthrenes 9 by a combined directed ortho metalation (DoM)-Suzuki
      Miyaura cross-coupling-directed remote metalation (DreM) sequence is reported.
      Diversity to this methodology was achieved by a regioselective DoM rather than
      DreM reaction, affording more highly substituted phenanthrols ( Table 2 ).
      Application of the turbo-Grignard reagent (i-PrMgCl.LiCl) in the Ni-catalyzed
      Corriu-Kumada reaction gave efficient decarbamoylation ( Tables 3 and 4 ).
      Additional features are the TMS protecting group and halo-induced ipso
      desilylation tactics applied to the regioselective synthesis of phenanthrenes (
      Scheme 2 ). 

PMID- 26301488
TI  - Long-acting muscarinic antagonists (LAMA) added to inhaled corticosteroids (ICS)
      versus the same dose of ICS alone for adults with asthma.
AB  - BACKGROUND: Despite the availability of several evidence-based therapies and non
      pharmacological strategies to improve control of symptoms and prevent
      exacerbations of asthma, patients with asthma continue to be at risk for
      mortality and morbidity.Previous trials have demonstrated the potentially
      beneficial effects of the long-acting muscarinic antagonist (LAMA) tiotropium on
      lung function in patients with asthma; however, a definitive conclusion on the
      benefit of LAMA in asthma is lacking, as is information on where in the current
      step-wise management strategy they would be most beneficial. OBJECTIVES: To
      assess the efficacy and safety of a LAMA added to any dose of an inhaled
      corticosteroid (ICS) compared with the same dose of ICS alone for adults whose
      asthma is not well controlled. SEARCH METHODS: We searched the Cochrane Airways
      Group Specialised Register (CAGR) from inception to April 2015, and we imposed no
      restriction on language of publication. We also searched clinicaltrials.gov, the
      World Health Organization (WHO) trials portal and drug company registries to
      identify unpublished studies. SELECTION CRITERIA: We searched for parallel and
      cross-over randomised controlled trials in which adults whose asthma was not well
      controlled by ICS alone were randomly assigned to receive LAMA add-on or placebo
      (both combined with ICS) for at least 12 weeks. DATA COLLECTION AND ANALYSIS: Two
      review authors independently screened the searches and extracted data from study
      reports. We used Covidence for duplicate screening, extraction of study
      characteristics and numerical data and risk of bias ratings. Pre-specified
      primary outcomes included exacerbations requiring oral corticosteroids, quality
      of life and all-cause serious adverse events. MAIN RESULTS: We identified five
      studies that met the inclusion criteria. All studies applied a double-blind,
      double-dummy design, and the population of all studies totalled 2563 adult
      participants. Study duration ranged from 12 weeks to 52 weeks, and risk of bias
      across domains in all studies was low. Trials included more women than men (33%
      to 47% male), and mean age of participants ranged from 41 to 48 years.
      Participants generally had a long history of asthma, and mean baseline predicted
      forced expiratory volume in one second (FEV1) was between 72% and 75% in three
      studies reporting pre-bronchodilator values.The rate of exacerbations requiring
      oral corticosteroids (OCS) was lower in patients prescribed an LAMA add-on than
      in those receiving the same dose of ICS alone (odds ratio (OR) 0.65, 95%
      confidence interval (CI) 0.46 to 0.93; 2277 participants; four studies; I(2) =
      0%; high-quality evidence), meaning that 27 fewer people per 1000 would have an
      exacerbation over 21 weeks requiring OCS with LAMA compared with ICS alone (95%
      CI 42 fewer to 6 fewer).All-cause serious adverse events (SAEs) and exacerbations
      requiring hospital admission were rare and the effects too imprecise to permit
      firm conclusions, but effects suggested that LAMA add-on may be associated with
      fewer of both compared with ICS alone (SAEs: OR 0.60, 95% CI 0.23 to 1.57; 2532
      participants; four studies; low-quality evidence; exacerbations requiring
      hospital admission: OR 0.42, 95% CI 0.12 to 1.47; 2562 participants; five
      studies; moderate-quality evidence). Additional therapy with a LAMA showed no
      clear benefit in terms of quality of life compared with ICS given alone; high
      quality evidence showed only a small mean improvement in quality of life as
      measured on the Asthma Quality of Life Questionnaire (AQLQ), which was not
      statistically significant. The same was true for asthma control as measured on
      the Asthma Control Questionnaire (ACQ), which was based on moderate-quality
      evidence. LAMA combined with ICS showed consistent benefit in a range of lung
      function measures compared with the same dose of ICS alone, and LAMA was not
      associated with significantly higher rates of adverse events than were reported
      with placebo. AUTHORS' CONCLUSIONS: For adults taking ICS for asthma without a
      long-acting beta2-agonist (LABA), LAMA given as add-on treatment reduces the
      likelihood of exacerbations requiring treatment with OCS and improves lung
      function. The benefits of LAMA combined with ICS for hospital admissions, all
      cause serious adverse events, quality of life and asthma control remain
      unknown.Results of this review, along with findings of related reviews conducted
      to assess the use of LAMA in other clinical scenarios involving asthma, can help
      to define the role of LAMA in the management of asthma. Trials of longer duration
      (up to 52 weeks) would provide a better opportunity to observe rare events such
      as serious adverse events and exacerbations requiring hospital admission.

PMID- 26301490
TI  - Noncontact Atomic Force Microscopy: An Emerging Tool for Fundamental Catalysis
      Research.
AB  - Although atomic force microscopy (AFM) was rapidly adopted as a routine surface
      imaging apparatus after its introduction in 1986, it has not been widely used in
      catalysis research. The reason is that common AFM operating modes do not provide
      the atomic resolution required to follow catalytic processes; rather the more
      complex noncontact (NC) mode is needed. Thus, scanning tunneling microscopy has
      been the principal tool for atomic scale catalysis research. In this Account,
      recent developments in NC-AFM will be presented that offer significant advantages
      for gaining a complete atomic level view of catalysis. The main advantage of NC
      AFM is that the image contrast is due to the very short-range chemical forces
      that are of interest in catalysis. This motivated our development of 3D-AFM, a
      method that yields quantitative atomic resolution images of the potential energy
      surfaces that govern how molecules approach, stick, diffuse, and rebound from
      surfaces. A variation of 3D-AFM allows the determination of forces required to
      push atoms and molecules on surfaces, from which diffusion barriers and
      variations in adsorption strength may be obtained. Pushing molecules towards each
      other provides access to intermolecular interaction between reaction partners.
      Following reaction, NC-AFM with CO-terminated tips yields textbook images of
      intramolecular structure that can be used to identify reaction intermediates and
      products. Because NC-AFM and STM contrast mechanisms are distinct, combining the
      two methods can produce unique insight. It is demonstrated for surface-oxidized
      Cu(100) that simultaneous 3D-AFM/STM yields resolution of both the Cu and O
      atoms. Moreover, atomic defects in the Cu sublattice lead to variations in the
      reactivity of the neighboring O atoms. It is shown that NC-AFM also allows a
      straightforward imaging of work function variations which has been used to
      identify defect charge states on catalytic surfaces and to map charge transfer
      within an individual molecule. These advances highlight the potential for NC-AFM
      based methods to become the cornerstone upon which a quantitative atomic scale
      view of each step of a catalytic process may be gained. Realizing this potential
      will rely on two breakthroughs: (1) development of robust methods for tip
      functionalization and (2) simplification of NC-AFM instrumentation and control
      schemes. Quartz force sensors may offer paths forward in both cases. They allow
      any material with an atomic asperity to be used as a tip, opening the door to a
      wide range of surface functionalization chemistry. In addition, they do not
      suffer from the instabilities that motivated the initial adoption of complex
      control strategies that are still used today. 

PMID- 26301489
TI  - Engineering Photosystem I Complexes with Metal Oxide Binding Peptides for
      Bioelectronic Applications.
AB  - Conventional dye-sensitized solar cells comprise semiconducting anodes sensitized
      with complex synthetic organometallic dyes, a platinum counter electrode, and a
      liquid electrolyte. This work focuses on replacing synthetic dyes with a
      naturally occurring biological pigment-protein complex known as Photosystem I
      (PSI). Specifically, ZnO binding peptides (ZOBiP)-fused PSI subunits (ZOBiP-PsaD
      and ZOBiP-PsaE) and TiO2 binding peptides (TOBiP)-fused ferredoxin (TOBiP-Fd)
      have been produced recombinantly from Escherichia coli. The MOBiP-fused peptides
      have been characterized via western blotting, circular dichroism, MALDI-TOF, and
      cyclic voltammetry. ZOBiP-PSI subunits have been used to replace wild-type PsaD
      and PsaE, and TOBiP-Fd has been chemically cross-linked to the stromal hump of
      PSI. These MOBiP peptides and MOBiP-PSI complexes have been produced and
      incubated with various metal oxide nanoparticles, showing increased binding when
      compared to that of wild-type PSI complexes. 

PMID- 26301482
TI  - Design and fine-tuning redox potentials of metalloproteins involved in electron
      transfer in bioenergetics.
AB  - Redox potentials are a major contributor in controlling the electron transfer
      (ET) rates and thus regulating the ET processes in the bioenergetics. To maximize
      the efficiency of the ET process, one needs to master the art of tuning the redox
      potential, especially in metalloproteins, as they represent major classes of ET
      proteins. In this review, we first describe the importance of tuning the redox
      potential of ET centers and its role in regulating the ET in bioenergetic
      processes including photosynthesis and respiration. The main focus of this review
      is to summarize recent work in designing the ET centers, namely cupredoxins,
      cytochromes, and iron-sulfur proteins, and examples in design of protein networks
      involved these ET centers. We then discuss the factors that affect redox
      potentials of these ET centers including metal ion, the ligands to metal center
      and interactions beyond the primary ligand, especially non-covalent secondary
      coordination sphere interactions. We provide examples of strategies to fine-tune
      the redox potential using both natural and unnatural amino acids and native and
      nonnative cofactors. Several case studies are used to illustrate recent successes
      in this area. Outlooks for future endeavors are also provided. This article is
      part of a Special Issue entitled Biodesign for Bioenergetics--the design and
      engineering of electronic transfer cofactors, proteins and protein networks,
      edited by Ronald L. Koder and J.L. Ross Anderson.

PMID- 26301491
TI  - Determination of in Vivo Enzyme Occupancy Utilizing Inhibitor Dissociation
      Kinetics.
AB  - During drug discovery, assessment of in vivo target occupancy by therapeutic
      candidates is often required for predicting clinical efficacy. Current strategies
      for determining target occupancy include using radiolabeled or irreversible
      surrogates, which can be technically challenging, and the results are often not
      sufficiently quantitative. We developed a straightforward method by applying slow
      dissociation kinetics to quantitatively determine enzyme occupancy without using
      specialized reagents. We applied this method to determine occupancy of Cathepsin
      K inhibitors in bone tissues harvested from rabbit femurs. Tissues from dosed
      animals were harvested, flash frozen, lysed, then analyzed by a jump-dilution
      assay with substrate. The rate of substrate turnover was monitored continuously
      until reaching steady state and progress curves were fit with the equation
      [product] = vst + ((vi - vs)/kobs)(1 - exp(-kobst)). The initial rate vi
      represents the residual activity of the enzyme before inhibitor dissociation; vs
      is the reaction rate after dissociation of the inhibitor. Occupancy is derived
      from the ratio of vi/vs. A significant benefit of the method is that data from
      both the occupied and unoccupied states are obtained in the same assay under
      identical conditions, which provides greater consistency between studies. The Cat
      K inhibitor MK-0674 (in vitro IC50 1 nM) was tested in young rabbits (<6 month
      old) and showed a dose-dependent increase in occupancy, reaching essentially
      complete occupancy at 1.0 mg/kg. In addition the method enables measurement of
      the total Cat K in the target tissue. Results confirmed complete occupancy even
      as the osteoclasts responded to higher doses with increased enzyme production. 

PMID- 26301493
TI  - White-Light-Emitting Lanthanide Metallogels with Tunable Luminescence and
      Reversible Stimuli-Responsive Properties.
AB  - We have developed model light-emitting metallogels functionalized with lanthanide
      metal-ligand coordination complexes via a terpyridyl-end-capped four-arm
      poly(ethylene glycol) polymer. The optical properties of these highly luminescent
      polymer networks are readily modulated over a wide spectrum, including white
      light emission, simply by tuning of the lanthanide metal ion stoichiometry.
      Furthermore, the dynamic nature of the Ln-N coordination bonding leads to a broad
      variety of reversible stimuli-responsive properties (mechano-, vapo-, thermo-,
      and chemochromism) of both sol-gel systems and solid thin films. The versatile
      functional performance combined with the ease of assembly suggests that this
      lanthanide coordination polymer design approach offers a robust pathway for
      future engineering of multi-stimuli-responsive polymer materials. 

PMID- 26301492
TI  - Tumor-Specific Formation of Enzyme-Instructed Supramolecular Self-Assemblies as
      Cancer Theranostics.
AB  - Despite the effort of developing various nanodelivery systems, most of them
      suffer from undesired high uptakes by the reticuloendothelial system, such as
      liver and spleen. Herein we develop an endogenous phosphatase-triggered
      coassembly strategy to form tumor-specific indocyanine green (ICG)-doped
      nanofibers (5) for cancer theranostics. Based on coordinated intermolecular
      interactions, 5 significantly altered near-infrared absorbance of ICG, which
      improves the critical photoacoustic and photothermal properties. The phosphatase
      instructed coassembly process, as well as its theranostic capability, was
      successfully conducted at different levels ranging from in vitro, living cell,
      tissue mimic, to in vivo. Specifically, the tumor uptake of ICG was markedly
      increased to 15.05 +/- 3.78%ID/g, which was 25-fold higher than that of free ICG
      (0.59 +/- 0.24%ID/g) at 4 h after intravenous injection. The resulting ultrahigh
      T/N ratios (>15) clearly differentiated tumors from the surrounding normal
      tissue. Complete tumor elimination with high therapeutic accuracy has been
      successfully achieved upon laser irradiation (0.8 W/cm(2), 5 min) within 24-48 h
      postinjection. As the first example, in vivo formation of tumor-specific ICG
      doped nanofiber for PTT theranostics owns the immense potential for clinical
      translation of personalized nanomedicine with targeted drug delivery as well as
      for cancer theranostics. 

PMID- 26301494
TI  - Recurrent AAV2-related insertional mutagenesis in human hepatocellular
      carcinomas.
AB  - Hepatocellular carcinomas (HCCs) are liver tumors related to various etiologies,
      including alcohol intake and infection with hepatitis B (HBV) or C (HCV) virus.
      Additional risk factors remain to be identified, particularly in patients who
      develop HCC without cirrhosis. We found clonal integration of adeno-associated
      virus type 2 (AAV2) in 11 of 193 HCCs. These AAV2 integrations occurred in known
      cancer driver genes, namely CCNA2 (cyclin A2; four cases), TERT (telomerase
      reverse transcriptase; one case), CCNE1 (cyclin E1; three cases), TNFSF10 (tumor
      necrosis factor superfamily member 10; two cases) and KMT2B (lysine-specific
      methyltransferase 2B; one case), leading to overexpression of the target genes.
      Tumors with viral integration mainly developed in non-cirrhotic liver (9 of 11
      cases) and without known risk factors (6 of 11 cases), suggesting a pathogenic
      role for AAV2 in these patients. In conclusion, AAV2 is a DNA virus associated
      with oncogenic insertional mutagenesis in human HCC. 

PMID- 26301495
TI  - In situ single-cell analysis identifies heterogeneity for PIK3CA mutation and
      HER2 amplification in HER2-positive breast cancer.
AB  - Detection of minor, genetically distinct subpopulations within tumors is a key
      challenge in cancer genomics. Here we report STAR-FISH (specific-to-allele PCR
      FISH), a novel method for the combined detection of single-nucleotide and copy
      number alterations in single cells in intact archived tissues. Using this method,
      we assessed the clinical impact of changes in the frequency and topology of
      PIK3CA mutation and HER2 (ERBB2) amplification within HER2-positive breast cancer
      during neoadjuvant therapy. We found that these two genetic events are not always
      present in the same cells. Chemotherapy selects for PIK3CA-mutant cells, a minor
      subpopulation in nearly all treatment-naive samples, and modulates genetic
      diversity within tumors. Treatment-associated changes in the spatial distribution
      of cellular genetic diversity correlated with poor long-term outcome following
      adjuvant therapy with trastuzumab. Our findings support the use of in situ single
      cell-based methods in cancer genomics and imply that chemotherapy before HER2
      targeted therapy may promote treatment resistance. 

PMID- 26301496
TI  - Broad H3K4me3 is associated with increased transcription elongation and enhancer
      activity at tumor-suppressor genes.
AB  - Tumor suppressors are mostly defined by inactivating mutations in tumors, yet
      little is known about their epigenetic features in normal cells. Through
      integrative analysis of 1,134 genome-wide epigenetic profiles, mutations from
      >8,200 tumor-normal pairs and our experimental data from clinical samples, we
      discovered broad peaks for trimethylation of histone H3 at lysine 4 (H3K4me3;
      wider than 4 kb) as the first epigenetic signature for tumor suppressors in
      normal cells. Broad H3K4me3 is associated with increased transcription elongation
      and enhancer activity, which together lead to exceptionally high gene expression,
      and is distinct from other broad epigenetic features, such as super-enhancers.
      Genes with broad H3K4me3 peaks conserved across normal cells may represent pan
      cancer tumor suppressors, such as TP53 and PTEN, whereas genes with cell type
      specific broad H3K4me3 peaks may represent cell identity genes and cell type
      specific tumor suppressors. Furthermore, widespread shortening of broad H3K4me3
      peaks in cancers is associated with repression of tumor suppressors. Thus, the
      broad H3K4me3 epigenetic signature provides mutation-independent information for
      the discovery and characterization of new tumor suppressors.

PMID- 26301499
TI  - Preferential Solvation of Lithium Cations and Impacts on Oxygen Reduction in
      Lithium-Air Batteries.
AB  - The solvation of Li+ with 11 nonaqueous solvents commonly used as electrolytes
      for lithium batteries was studied. The solvation preferences of different
      solvents were compared by means of electrospray mass spectrometry and collision
      induced dissociation. The relative strength of the solvent for the solvation of
      Li+ was determined. The Lewis acidity of the solvated Li+ cations was determined
      by the preferential solvation of the solvent in the solvation shell. The kinetics
      of the catalytic disproportionation of the O2*- depends on the relative Lewis
      acidity of the solvated Li+ ion. The impact of the solvated Li+ cation on the O2
      redox reaction was also investigated.

PMID- 26301498
TI  - Empiric Monotherapy Versus Combination Therapy for Enterobacteriaceae Bacteremia
      in Children.
AB  - BACKGROUND: Bacteremia caused by members of the Enterobacteriaceae can be life
      threatening. Appropriate antimicrobial therapy is critical to reducing morbidity
      and mortality. METHODS: This retrospective cohort study (2008-2011) was conducted
      in children and young adults (<21 years of age) hospitalized with
      Enterobacteriaceae bacteremia with clinical signs and symptoms of infection. We
      investigated whether combination empiric antimicrobial therapy was superior to
      monotherapy for treatment. Monotherapy was defined as empiric therapy with a beta
      lactam agent alone. Combination therapy was defined as coadministration of a beta
      lactam agent with an aminoglycoside agent for at least 48 hours before the
      susceptibility data were known. Outcome was measured as the response to therapy
      (defined as the time to negative blood culture) and was compared among patients
      administered monotherapy versus combination therapy. RESULTS: Of 203 episodes of
      Enterobacteriaceae bacteremia, 78 (38%) were caused by Klebsiella spp, 73 (36%)
      were caused by Escherichia coli, and 52 (26%) were caused by Enterobacter spp. Of
      203 episodes of bacteremia caused by 3 organisms of greatest interest, 101 (50%)
      were treated with combination therapy. Patients with cancer were more likely to
      receive combination therapy (38% vs. 16%; P < 0.001); patients with
      gastrointestinal disease and those receiving total parenteral nutrition were more
      likely to receive monotherapy (58% vs. 39%; P = 0.006 and 54% vs. 37%; P = 0.013,
      respectively). There was no difference in outcome in patients receiving
      monotherapy versus combination therapy (P = 0.86). CONCLUSION: Combination
      therapy consisting of a beta-lactam agent and an aminoglycoside agent was not
      superior to monotherapy with a beta-lactam agent alone for managing
      Enterobacteriaceae bacteremia in children and young adults.

PMID- 26301500
TI  - Diallyl Trisulfide Is a Fast H2S Donor, but Diallyl Disulfide Is a Slow One: The
      Reaction Pathways and Intermediates of Glutathione with Polysulfides.
AB  - Diallyl trisulfide (DATS) reacts rapidly with glutathione (GSH) to release H2S
      through thiol-disulfide exchange followed by allyl perthiol reduction by GSH. Yet
      diallyl disulfide (DADS) only releases a minute amount of H2S via a sluggish
      reaction with GSH through an alpha-carbon nucleophilic substitution pathway. The
      results clarify the misunderstanding of DADS as a rapid H2S donor, which is
      attributed to its DATS impurity. 

PMID- 26301497
TI  - Genetic association analyses highlight biological pathways underlying mitral
      valve prolapse.
AB  - Nonsyndromic mitral valve prolapse (MVP) is a common degenerative cardiac
      valvulopathy of unknown etiology that predisposes to mitral regurgitation, heart
      failure and sudden death. Previous family and pathophysiological studies suggest
      a complex pattern of inheritance. We performed a meta-analysis of 2 genome-wide
      association studies in 1,412 MVP cases and 2,439 controls. We identified 6 loci,
      which we replicated in 1,422 cases and 6,779 controls, and provide functional
      evidence for candidate genes. We highlight LMCD1 (LIM and cysteine-rich domains
      1), which encodes a transcription factor and for which morpholino knockdown of
      the ortholog in zebrafish resulted in atrioventricular valve regurgitation. A
      similar zebrafish phenotype was obtained with knockdown of the ortholog of TNS1,
      which encodes tensin 1, a focal adhesion protein involved in cytoskeleton
      organization. We also showed expression of tensin 1 during valve morphogenesis
      and describe enlarged posterior mitral leaflets in Tns1(-/-) mice. This study
      identifies the first risk loci for MVP and suggests new mechanisms involved in
      mitral valve regurgitation, the most common indication for mitral valve repair. 

PMID- 26301501
TI  - Development of Chinese reference man deformable surface phantom and its
      application to the influence of physique on electromagnetic dosimetry.
AB  - A reference man is a theoretical individual that represents the average
      anatomical structure and physiological and metabolic features of a specific group
      of people and has been widely used in radiation safety research. With the help of
      an advantage in deformation, the present work proposed a Chinese reference man
      adult-male polygon-mesh surface phantom based on the Visible Chinese Human
      segment image dataset by surface rendering and deforming. To investigate the
      influence of physique on electromagnetic dosimetry in humans, a series of human
      phantoms with 10th, 50th and 90th body mass index and body circumference
      percentile physiques for Chinese adult males were further constructed by
      deforming the Chinese reference man surface phantom. All the surface phantoms
      were then voxelized to perform electromagnetic field simulation in a frequency
      range of 20 MHz to 3 GHz using the finite-difference time-domain method and
      evaluate the whole-body average and organ average specific absorption rate and
      the ratios of absorbed energy in skin, fat and muscle to the whole body. The
      results indicate thinner physique leads to higher WBSAR and the volume of
      subcutaneous fat, the penetration depth of the electromagnetic field in tissues
      and standing-wave occurrence may be the influence factors of physique on
      electromagnetic dosimetry.

PMID- 26301502
TI  - FMNL1, a key regulator for asymmetric cell division.

PMID- 26301503
TI  - Ultrafast Deactivation of the pipi*(V) State of Ethylene Studied Using Sub-20 fs
      Time-Resolved Photoelectron Imaging.
AB  - The ultrafast deactivation process of ethylene in the pipi*(V) state was studied
      using time-resolved photoelectron imaging with sub-20 fs pulses at 159 and 198
      nm. The photoelectron kinetic energy distribution observed upon 159 nm
      photoexcitation exhibited a continuous downward shift within 20 fs, attributed to
      both C-C twist and pyramidalization motions. A partial revival of the vibrational
      wave packet was observed with the period of about 18 fs, which is attributed to
      the C-C twist from 0 to 180 degrees  on the pipi*(V) potential energy surface.
      Signature for internal conversion from the pipi*(V) state to a lower-lying pi3s
      Rydberg (R) state, which has been previously suggested, was not detected in the
      time-dependent photoelectron kinetic energy and angular distributions. 

PMID- 26301504
TI  - Urine Albumin Excretion Is Associated with Cardiac Troponin T Detected with a
      Highly Sensitive Assay in a Community-Based Population.
AB  - BACKGROUND: Urine albumin excretion is an important predictor of adverse
      cardiovascular events. Minimally elevated levels of serum cardiac troponin T
      (cTnT), a marker of cardiomyocyte micronecrosis, can be detected with high
      sensitivity cTnT (hs-cTnT) assays. The purpose of this study was to investigate
      the relationship between alterations in albuminuria and serum hs-cTnT levels in a
      community-based population. METHODS: We examined the association between the
      urine albumin/creatinine ratio (UACR) and hs-cTnT levels in 1354 participants
      without overt cardiovascular disease in a community-based, cross-sectional study
      in Beijing, China. RESULTS: With the highly sensitive assay, cTnT levels were
      detectable in 90.5% of our subjects. The median (interquartile range)
      concentrations of hs-cTnT were 7 (5-10) pg/mL. After adjustment for several
      factors, UACR (odds ratio: 1.40; 95% confidence interval: 1.08-1.65; P = 0.002)
      was associated with a higher likelihood of elevated hs-cTnT (>=14 pg/ mL),
      whereas the relationship between UACR and a higher presence of detectable hs-cTnT
      (>= 3 pg/ mL) was not significant. In addition, a fully adjusted logistic
      regression analysis revealed that compared with participants in the lowest UACR
      quartile, those in the highest quartile had a 2.43- fold (95% CI: 1.25-5.08; P =
      0.006) increased risk of elevated hs-cTnT. CONCLUSIONS: Higher urine albumin
      excretion is associated with elevated hs-cTnT among persons without clinically
      evident cardiovascular disease, suggesting that albuminuria may be a potential
      risk factor for subclinical cardiovascular disease in the general population.

PMID- 26301505
TI  - Experimental Investigation of Mechanical and Thermal Properties of Silica
      Nanoparticle-Reinforced Poly(acrylamide) Nanocomposite Hydrogels.
AB  - Current studies investigating properties of nanoparticle-reinforced polymers have
      shown that nanocomposites often exhibit improved properties compared to neat
      polymers. However, over two decades of research, using both experimental studies
      and modeling analyses, has not fully elucidated the mechanistic underpinnings
      behind these enhancements. Moreover, few studies have focused on developing an
      understanding among two or more polymer properties affected by incorporation of
      nanomaterials. In our study, we investigated the elastic and thermal properties
      of poly(acrylamide) hydrogels containing silica nanoparticles. Both nanoparticle
      concentration and size affected hydrogel properties, with similar trends in
      enhancements observed for elastic modulus and thermal diffusivity. We also
      observed significantly lower swellability for hydrogel nanocomposites relative to
      neat hydrogels, consistent with previous work suggesting that nanoparticles can
      mediate pseudo crosslinking within polymer networks. Collectively, these results
      indicate the ability to develop next-generation composite materials with enhanced
      mechanical and thermal properties by increasing the average crosslinking density
      using nanoparticles. 

PMID- 26301507
TI  - Towards a Computable Data Corpus of Temporal Correlations between Drug
      Administration and Lab Value Changes.
AB  - BACKGROUND: The analysis of electronic health records for an automated detection
      of adverse drug reactions is an approach to solve the problems that arise from
      traditional methods like spontaneous reporting or manual chart review. Algorithms
      addressing this task should be modeled on the criteria for a standardized case
      causality assessment defined by the World Health Organization. One of these
      criteria is the temporal relationship between drug intake and the occurrence of a
      reaction or a laboratory test abnormality. Appropriate data that would allow for
      developing or validating related algorithms is not publicly available, though.
      METHODS: In order to provide such data, retrospective routine data of drug
      administrations and temporally corresponding laboratory observations from a
      university clinic were extracted, transformed and evaluated by experts in terms
      of a reasonable time relationship between drug administration and lab value
      alteration. RESULT: The result is a data corpus of 400 episodes of normalized
      laboratory parameter values in temporal context with drug administrations. Each
      episode has been manually classified whether it contains data that might indicate
      a temporal correlation between the drug administration and the change of the lab
      value course, whether such a change is not observable or whether a decision
      between those two options is not possible due to the data. In addition, each
      episode has been assigned a concordance value which indicates how difficult it is
      to assess. This is the first open data corpus of a computable ground truth of
      temporal correlations between drug administration and lab value alterations.
      DISCUSSION: The main purpose of this data corpus is the provision of data for
      further research and the provision of a ground truth which allows for comparing
      the outcome of other assessments of this data with the outcome of assessments
      made by human experts. It can serve as a contribution towards systematic,
      computerized ADR detection in retrospective data. With this lab value curve data
      as a basis, algorithms for detecting temporal relationships can be developed, and
      with the classification made by human experts, these algorithms can immediately
      be validated. Due to the normalization of the lab value data, it allows for a
      generic approach rather than for specific or solitary drug/lab value
      combinations.

PMID- 26301506
TI  - Cancer Cell Growth Is Differentially Affected by Constitutive Activation of NRF2
      by KEAP1 Deletion and Pharmacological Activation of NRF2 by the Synthetic
      Triterpenoid, RTA 405.
AB  - Synthetic triterpenoids are antioxidant inflammation modulators (AIMs) that
      exhibit broad anticancer activity. AIMs bind to KEAP1 and inhibit its ability to
      promote NRF2 degradation. As a result, NRF2 increases transcription of genes that
      restore redox balance and reduce inflammation. AIMs inhibit tumor growth and
      metastasis by increasing NRF2 activity in the tumor microenvironment and by
      modulating the activity of oncogenic signaling pathways, including NF-kappaB, in
      tumor cells. Accumulating evidence suggests that KEAP1 loss or mutation--which
      results in high levels of sustained NRF2 activity--may promote cancer growth and
      increase chemoresistance. Loss of KEAP1 also increases the levels of other
      oncogenic proteins, including IKKbeta and BCL2. The apparent survival advantage
      provided to some tumor cells by loss of functional KEAP1 raises the question of
      whether pharmacological inhibition of KEAP1 could promote tumor growth. To
      address this issue, we characterized the basal levels of KEAP1 and NRF2 in a
      panel of human tumor cell lines and profiled the activity of an AIM, RTA 405. We
      found that in tumor cell lines with low or mutant KEAP1, and in Keap1-/- murine
      embryonic fibroblasts, multiple KEAP1 targets including NRF2, IKKbeta, and BCL2
      were elevated. Keap1-/- murine embryonic fibroblasts also had higher rates of
      proliferation and colony formation than their wild-type counterparts. In cells
      with functional KEAP1, RTA 405 increased NRF2 levels, but not IKKbeta or BCL2
      levels, and did not increase cell proliferation or survival. Moreover, RTA 405
      inhibited growth at similar concentrations in cells with different basal NRF2
      activity levels and in cells with wild-type or mutant KRAS. Finally, pre
      treatment with RTA 405 did not protect tumor cells from doxorubicin- or cisplatin
      mediated growth inhibition. Collectively, these data demonstrate that
      pharmacological activation of NRF2 by AIMs is distinct from genetic activation
      and does not provide a growth or survival advantage to tumor cells.

PMID- 26301508
TI  - Listening to Music during Warming-Up Counteracts the Negative Effects of Ramadan
      Observance on Short-Term Maximal Performance.
AB  - AIM: The aim of the present study was to examine whether listening to music
      during warming-up might influence short-term maximal performance (STMP),
      cognitive anxiety, self-confidence, and enjoyment during Ramadan, and whether
      these affects might predict STMP. METHODS: Nine male physical education students
      (age: 21 +/- 1.1 years; height: 1.8 +/- 0.04 m; body mass: 83 +/- 5 kg)
      volunteered to participate in the present study. A within-subjects design
      consisted of four experimental sessions: Two sessions occurred one week before
      Ramadan and two others took place during Ramadan. They were scheduled at 5 p.m.
      and were conducted as follows: After a 10-minute warm-up either with or without
      listening to music, each participant performed a 5-m multiple shuttle run test,
      after which he was asked to answer items intended to assess his affective state
      during the experimental task. RESULTS: Our findings revealed that STMP was lower
      during Ramadan than before Ramadan in the no-music condition. Additionally, it
      was found that STMP was higher in the music condition than in the no-music
      condition during Ramadan, and that STMP measured before Ramadan did not differ
      from that measured during Ramadan in the music condition. Regarding affects, the
      findings revealed that enjoyment was lower during Ramadan than before Ramadan in
      the music condition, and that cognitive anxiety was lower in the music condition
      than in the no-music condition before Ramadan. Self-confidence was not influenced
      by the experimental conditions. CONCLUSION: This study showed that listening to
      music during warming-up not only would be beneficial for STMP in Ramadan fasters,
      but also would counteract the negative effects of Ramadan observance on STMP.

PMID- 26301509
TI  - Modelling the Northward Expansion of Culicoides sonorensis (Diptera:
      Ceratopogonidae) under Future Climate Scenarios.
AB  - Climate change is affecting the distribution of pathogens and their arthropod
      vectors worldwide, particularly at northern latitudes. The distribution of
      Culicoides sonorensis (Diptera: Ceratopogonidae) plays a key role in affecting
      the emergence and spread of significant vector borne diseases such as Bluetongue
      (BT) and Epizootic Hemorrhagic Disease (EHD) at the border between USA and
      Canada. We used 50 presence points for C. sonorensis collected in Montana (USA)
      and south-central Alberta (Canada) between 2002 and 2012, together with monthly
      climatic and environmental predictors to develop a series of alternative maximum
      entropy distribution models. The best distribution model under current climatic
      conditions was selected through the Akaike Information Criterion, and included
      four predictors: Vapour Pressure Deficit of July, standard deviation of
      Elevation, Land Cover and mean Precipitation of May. This model was then
      projected into three climate change scenarios adopted by the IPCC in its 5th
      assessment report and defined as Representative Concentration Pathways (RCP) 2.6,
      4.5 and 8.5. Climate change data for each predictor and each RCP were calculated
      for two time points pooling decadal data around each one of them: 2030 (2021
      2040) and 2050 (2041-2060). Our projections showed that the areas predicted to be
      at moderate-high probability of C. sonorensis occurrence would increase from the
      baseline scenario to 2030 and from 2030 to 2050 for each RCP. The projection also
      indicated that the current northern limit of C. sonorensis distribution is
      expected to move northwards to above 53 degrees N. This may indicate an increased
      risk of Culicoides-borne diseases occurrence over the next decades, particularly
      at the USA-Canada border, as a result of changes which favor C. sonorensis
      presence when associated to other factors (i.e. host and pathogen factors).
      Recent observations of EHD outbreaks in northern Montana and southern Alberta
      supported our projections and considerations. The results of this study can
      inform the development of cost effective surveillance programs, targeting areas
      within the predicted limits of C. sonorensis geographical occurrence under
      current and future climatic conditions. 

PMID- 26301511
TI  - Reductions in quality of life associated with common mental disorders: results
      from a nationally representative sample.
AB  - OBJECTIVE: Traditional burden-of-disease estimates often exclude personality
      disorders, which are associated with significant mortality and morbidity. The aim
      of this study was to estimate the health-related quality of life (HRQoL) and
      annual population-level quality-adjusted life-year (QALY) losses associated with
      different mental and physical health conditions. In particular, it sought to
      quantify the impact of personality disorders on quality of life, at an individual
      and population level. METHOD: This was a secondary analysis of data from the
      National Epidemiologic Survey on Alcohol and Related Conditions, a nationally
      representative survey of the US general population collected from 2001 to 2005 (N
      = 34,653). Health-related quality of life (measured using the Short-Form Health
      Survey-6D) was the main outcome of interest. Regression analysis assessed the
      impact of various mental (based on DSM-IV criteria) and physical health
      conditions on HRQoL scores, and this impact was combined with the prevalence of
      disorders to estimate the population-level burden of disease. RESULTS: Mood
      disorders were associated with the highest decrease in HRQoL scores, followed by
      strokes, psychotic illness, and arthritis (P < .01). The greatest annual
      population QALY losses were caused by arthritis, mood disorders, and personality
      disorders. CONCLUSIONS: Quality-adjusted life year losses associated with
      personality disorders ranked behind only mood disorders and arthritis.
      Personality disorders were associated with significant reductions in quality of
      life, despite the fact that they are often excluded from traditional burden of
      disease estimates.

PMID- 26301512
TI  - Isolation of Rickettsia massiliae from Rhipicephalus sanguineus Ticks, Buenos
      Aires (Argentina).
AB  - Rickettsia massiliae , a member of the spotted fever group of Rickettsia, was
      first isolated from a Rhipicephalus turanicus tick in France. In the New World,
      it has been detected in Rhipicephalus sanguineus ticks from different
      geographical locations in Argentina and the United States, but it has only been
      isolated in Arizona. The aim of this study was the isolation and genetic
      characterization of R. massiliae from R. sanguineus ticks collected from dogs in
      Buenos Aires city, Argentina. In total, 49 R. sanguineus ticks were collected
      from 10 dogs and grouped into 10 pools of 4-5 specimens. With a PCR assay, which
      detects a fragment of the Rickettsia genus-specific 23S-5S intergenic space, 1
      pool of 5 ticks was found positive. Generated sequences exhibited 100% identity
      with R. massiliae . A new isolate, named CABA, was obtained from this pool by
      inoculating it into monolayers of Vero cells. Genotypic characteristics were
      determined, and results showed that fragments of the 23S-5S intergenic space,
      ompA, ompB, gltA, htrA, and sca1 genes had great similarity with R. massiliae
      strain Bar29 (Spain). Although few human cases have been confirmed for this
      pathogen, its circulation in urban areas is of great importance to public health.
      This isolation improves knowledge of the circulating pathogen and could improve
      future diagnostic processes as it allows the production of more specific antigens
      for serological testing. 

PMID- 26301510
TI  - First Detection of an Enterovirus C99 in a Captive Chimpanzee with Acute Flaccid
      Paralysis, from the Tchimpounga Chimpanzee Rehabilitation Center, Republic of
      Congo.
AB  - Enteroviruses, members of the Picornaviridae family, are ubiquitous viruses
      responsible for mild to severe infections in human populations around the world.
      In 2010 Pointe-Noire, Republic of Congo recorded an outbreak of acute flaccid
      paralysis (AFP) in the humans, caused by wild poliovirus type 1 (WPV1). One month
      later, in the Tchimpounga sanctuary near Pointe-Noire, a chimpanzee developed
      signs similar to AFP, with paralysis of the lower limbs. In the present work, we
      sought to identify the pathogen, including viral and bacterial agents,
      responsible for this illness. In order to identify the causative agent, we
      evaluated a fecal specimen by PCR and sequencing. A Human enterovirus C,
      specifically of the EV-C99 type was potentially responsible for the illness in
      this chimpanzee. To rule out other possible causative agents, we also
      investigated the bacteriome and the virome using next generation sequencing. The
      majority of bacterial reads obtained belonged to commensal bacteria (95%), and
      the mammalian virus reads matched mainly with viruses of the Picornaviridae
      family (99%), in which enteroviruses were the most abundant (99.6%). This study
      thus reports the first identification of a chimpanzee presenting AFP most likely
      caused by an enterovirus and demonstrates once again the cross-species
      transmission of a human pathogen to an ape. 

PMID- 26301513
TI  - Curcumenol isolated from Curcuma zedoaria suppresses Akt-mediated NF-kappaB
      activation and p38 MAPK signaling pathway in LPS-stimulated BV-2 microglial
      cells.
AB  - Curcumenol, a sesquiterpene isolated from Curcuma zedoaria is known to possess a
      variety of health and medicinal values which includes neuroprotection, anti
      inflammatory, anti-tumor and hepatoprotective activities. The current study aim
      is to investigate the modulatory effects of curcumenol towards the
      lipopolysaccharides (LPS)-induced inflammation in BV-2 microglia. Curcumenol
      markedly decreased LPS-induced production of nitric oxide (NO), pro-inflammatory
      cytokines [(IL-6) and (TNF-alpha)] and pro-inflammatory proteins expression, iNOS
      and COX-2. Moreover, curcumenol inhibited NF-kappaB activation by suppressing the
      nuclear translocation of the NF-kappaB p65 subunit and blocking IkappaBalpha
      phosphorylation and degradation. Furthermore, an NF-kappaB inhibitor, ethyl 3,4
      dihydroxycinnamate also known as caffeic acid ethyl ester (CAEE), attenuated LPS
      stimulated iNOS and COX-2 expression, suggesting that NF-kappaB inhibition is a
      regulator in the expression of iNOS and COX-2 proteins. Further mechanistic study
      with an Akt inhibitor, triciribine hydrate (API-2), revealed that curcumenol
      acted through Akt-dependent NF-kappaB activation. Moreover, curcumenol inhibition
      on LPS-induced phosphorylation of p38 MAPK is confirmed by its inhibitor (SB
      202190). These results indicate that curcumenol diminishes the proinflammatory
      mediators and the expression of the regulatory genes in LPS-stimulated BV-2 by
      inhibiting Akt-dependent NF-kappaB activation and downregulation of Akt and p38
      MAPKs signaling. 

PMID- 26301515
TI  - Paternal and maternal warmth and the development of prosociality among
      preschoolers.
AB  - Although the influence of maternal behavior on child outcomes has been
      extensively studied, there has not been the same attention to the role of
      paternal behavior in development. This gap in research stands in contrast to the
      observable shift in parental roles and responsibilities in contemporary society.
      The goal of this study was to examine the roles of fathers, mothers, and children
      in the development of children's prosocial behavior. In the current study we
      examined the development of reciprocal relations between paternal and maternal
      behavior and child prosociality over 36 months. Three hundred eighty-one families
      were assessed when children were 18, 36, and 54 months of age. Fathers and
      mothers reported on their own warmth and negativity using standardized
      questionnaires. Child prosociality was measured using averaged parental reports.
      Actor-partner interdependence models revealed that paternal and maternal warmth
      predicted subsequent increases in child prosocial behavior, but child prosocial
      behavior did not predict subsequent parenting. Father and mother parenting
      practices were reciprocally interrelated. The results point to the important
      roles paternal and maternal warmth play in the development of children's
      prosocial behavior.

PMID- 26301514
TI  - Health risk behaviors and depressive symptoms among Hispanic adolescents:
      Examining acculturation discrepancies and family functioning.
AB  - Drawing from a theory of bicultural family functioning 2 models were tested to
      examine the longitudinal effects of acculturation-related variables on adolescent
      health risk behaviors and depressive symptoms (HRB/DS) mediated by caregiver and
      adolescent reports of family functioning. One model examined the effects of
      caregiver-adolescent acculturation discrepancies in relation to family
      functioning and HRB/DS. A second model examined the individual effects of
      caregiver and adolescent acculturation components in relation to family
      functioning and HRB/DS. A sample of 302 recently immigrated Hispanic caregiver
      child dyads completed measures of Hispanic and U.S. cultural practices, values,
      and identities at baseline (predictors); measures of family cohesion, family
      communications, and family involvement 6 months postbaseline (mediators); and
      only adolescents completed measures of smoking, binge drinking, inconsistent
      condom use, and depressive symptoms 1 year postbaseline (outcomes). Measures of
      family cohesion, family communications, and family involvement were used to
      conduct a confirmatory factor analysis to estimate the fit of a latent construct
      for family functioning. Key findings indicate that (a) adolescent acculturation
      components drove the effect of caregiver-adolescent acculturation discrepancies
      in relation to family functioning; (b) higher levels of adolescent family
      functioning were associated with less HRB/DS, whereas higher levels of caregiver
      family functioning were associated with more adolescent HRB/DS; (c) and only
      adolescent reports of family functioning mediated the effects of acculturation
      components and caregiver-adolescent acculturation discrepancies on HRB/DS.

PMID- 26301516
TI  - Micro-RNA-30a regulates ischemia-induced cell death by targeting heat shock
      protein HSPA5 in primary cultured cortical neurons and mouse brain after stroke.
AB  - Micro-RNAs (miRs) have emerged as key gene regulators in many diseases, including
      stroke. We recently reported that miR-30a protects N2A cells against ischemic
      injury, in part through enhancing beclin 1-mediated autophagy. The present study
      explores further the involvement of miR-30a in ischemia-induced apoptosis and its
      possible mechanisms in primary cortical neurons and stroked mouse brain. We
      demonstrate that miR-30a level is significantly decreased in cortical neurons
      after 1-hr oxygen-glucose deprivation (OGD)/24-hr reoxygenation. Overexpression
      of miR-30a aggravated the OGD-induced neuronal cell death, whereas inhibition of
      miR-30a attenuated necrosis and apoptosis as determined by 3-(4,5-dimethyl-2
      thiazolyl)-2,5-di-phenyl-2H-tetrazolium bromide, lactate dehydrogenase, TUNEL,
      and cleaved caspase-3. The amount of HSPA5 protein, which is predicted to be a
      putative target of miR-30a by TargetScan, could be reduced by pre-miR-30a,
      whereas it was increased by anti-miR-30a. Furthermore, the luciferase reporter
      assay confirmed that miR-30a directly binds to the predicted 3'-UTR target sites
      of the hspa5 gene. The cell injury regulated by miR-30a in OGD-treated cells
      could be aggravated by HSPA5 siRNA. We also observed an interaction of HSPA5 and
      caspase-12 by coimmunoprecipitation and speculate that HSPA5 might be involved in
      endoplasmic reticulum stress-induced apoptosis. In vivo, reduced miR-30a
      increased the HSPA5 level and attenuated ischemic brain infarction in focal
      ischemia-stroked mice. Downregulation of miR-30a could prevent neural ischemic
      injury through upregulating HSPA5 protein expression, and decreased ER stress
      induced apoptosis might be one of the mechanisms underlying HSPA5-mediated
      neuroprotection.

PMID- 26301518
TI  - Formation Pathways of Mono- to Octa-Chlorinated Dibenzo-p-dioxins and
      Dibenzofurans in Main Organochemical Industries.
AB  - The concentrations and formation pathways of mono- to octa-chlorinated dibenzo-p
      dioxins (PCDDs) and dibenzofurans (PCDFs) were investigated in main
      organochemical industries. High levels of PCDDs and PCDFs were detected. The
      total concentrations of 27 PCDD/F congeners in chloranil, 2,4-D, and 1,4
      dichlorobenzene were 5302397 +/- 8944449, 20963 +/- 15908, and 242 +/- 67 pg g(
      1), respectively, and the less-chlorinated PCDD/F levels were 12006 +/- 20155,
      9536 +/- 5594, and 195 +/- 94 pg g(-1), respectively. The distribution trends of
      less and more chlorinated PCDD/Fs were similar in different chemical plants
      because of their similar formation pathways, which may also be related to the
      degree of chlorination of chemical products and purification processes. 1,2,3,4
      TeCDF and 2,4,8-TrCDF were selected as model molecules to calculate the bond
      dissociation energy, showing that 2-MCDF, 3-MCDF, and 2,8-DCDF are more easily
      formatted as shown by the analytical results. The formation pathways of less to
      more chlorinated PCDFs are proposed to explain why 2-MoCDF, 2,8-DiCDF, 2,4,8
      TrCDF, and 2,3,4,7,8-PeCDF are the dominant congeners and to explain why
      2,3,4,7,8-PeCDF is the largest contributor of I-TEQs in most studies. 

PMID- 26301519
TI  - Effects of Action Observational Training Plus Brain-Computer Interface-Based
      Functional Electrical Stimulation on Paretic Arm Motor Recovery in Patient with
      Stroke: A Randomized Controlled Trial.
AB  - The purpose of this study was to investigate whether action observational
      training (AOT) plus brain-computer interface-based functional electrical
      stimulation (BCI-FES) has a positive influence on motor recovery of paretic upper
      extremity in patients with stroke. This was a hospital-based, randomized
      controlled trial with a blinded assessor. Thirty patients with a first-time
      stroke were randomly allocated to one of two groups: the BCI-FES group (n = 15)
      and the control group (n = 15). The BCI-FES group administered to AOT plus BCI
      FES on the paretic upper extremity five times per week during 4 weeks while both
      groups received conventional therapy. The primary outcomes were the Fugl-Meyer
      Assessment of the Upper Extremity, Motor Activity Log (MAL), Modified Barthel
      Index and range of motion of paretic arm. A blinded assessor evaluated the
      outcomes at baseline and 4 weeks. All baseline outcomes did not differ
      significantly between the two groups. After 4 weeks, the Fugl-Meyer Assessment of
      the Upper Extremity sub-items (total, shoulder and wrist), MAL (MAL-Activity of
      Use and Quality of Movement), Modified Barthel Index and wrist flexion range of
      motion were significantly higher in the BCI-FES group (p < 0.05). AOT plus BCI
      based FES is effective in paretic arm rehabilitation by improving the upper
      extremity performance. The motor improvements suggest that AOT plus BCI-based FES
      can be used as a therapeutic tool for stroke rehabilitation. The limitations of
      the study are that subjects had a certain limited level of upper arm function,
      and the sample size was comparatively small; hence, it is recommended that future
      large-scale trials should consider stratified and lager populations according to
      upper arm function.

PMID- 26301517
TI  - Multifaceted roles for astrocytes in spreading depolarization: A target for
      limiting spreading depolarization in acute brain injury?
AB  - Spreading depolarizations (SDs) are coordinated waves of synchronous
      depolarization, involving large numbers of neurons and astrocytes as they spread
      slowly through brain tissue. The recent identification of SDs as likely
      contributors to pathophysiology in human subjects has led to a significant
      increase in interest in SD mechanisms, and possible approaches to limit the
      numbers of SDs or their deleterious consequences in injured brain. Astrocytes
      regulate many events associated with SD. SD initiation and propagation is
      dependent on extracellular accumulation of K(+) and glutamate, both of which
      involve astrocytic clearance. SDs are extremely metabolically demanding events,
      and signaling through astrocyte networks is likely central to the dramatic
      increase in regional blood flow that accompanies SD in otherwise healthy tissues.
      Astrocytes may provide metabolic support to neurons following SD, and may provide
      a source of adenosine that inhibits neuronal activity following SD. It is also
      possible that astrocytes contribute to the pathophysiology of SD, as a
      consequence of excessive glutamate release, facilitation of NMDA receptor
      activation, brain edema due to astrocyte swelling, or disrupted coupling to
      appropriate vascular responses after SD. Direct or indirect evidence has
      accumulated implicating astrocytes in many of these responses, but much remains
      unknown about their specific contributions, especially in the context of injury.
      Conversion of astrocytes to a reactive phenotype is a prominent feature of
      injured brain, and recent work suggests that the different functional properties
      of reactive astrocytes could be targeted to limit SDs in pathophysiological
      conditions.

PMID- 26301521
TI  - Sex-specific behavioural symptoms of viral gut infection and Wolbachia in
      Drosophila melanogaster.
AB  - All organisms are infected with a range of symbionts spanning the spectrum of
      beneficial mutualists to detrimental parasites. The fruit fly Drosophila
      melanogaster is a good example, as both endosymbiotic Wolbachia, and pathogenic
      Drosophila C Virus (DCV) commonly infect it. While the pathophysiology and immune
      responses against both symbionts are the focus of intense study, the behavioural
      effects of these infections have received less attention. Here we report sex
      specific behavioural responses to these infections in D. melanogaster. DCV
      infection caused increased sleep in female flies, but had no detectable effect in
      male flies. The presence of Wolbachia did not reduce this behavioural response to
      viral infection. We also found evidence for a sex-specific cost of Wolbachia, as
      male flies infected with the endosymbiont became more lethargic when awake. We
      discuss these behavioural symptoms as potentially adaptive sickness behaviours. 

PMID- 26301520
TI  - Boron bridging of rhamnogalacturonan-II is promoted in vitro by cationic
      chaperones, including polyhistidine and wall glycoproteins.
AB  - Dimerization of rhamnogalacturonan-II (RG-II) via boron cross-links contributes
      to the assembly and biophysical properties of the cell wall. Pure RG-II is
      efficiently dimerized by boric acid (B(OH)3 ) in vitro only if nonbiological
      agents for example Pb(2+) are added. By contrast, newly synthesized RG-II domains
      dimerize very rapidly in vivo. We investigated biological agents that might
      enable this. We tested for three such agents: novel enzymes, borate-transferring
      ligands and cationic 'chaperones' that facilitate the close approach of two
      polyanionic RG-II molecules. Dimerization was monitored electrophoretically.
      Parsley shoot cell-wall enzymes did not affect RG-II dimerization in vitro.
      Borate-binding ligands (apiose, dehydroascorbic acid, alditols) and small organic
      cations (including polyamines) also lacked consistent effects. Polylysine bound
      permanently to RG-II, precluding electrophoretic analysis. However, another
      polycation, polyhistidine, strongly promoted RG-II dimerization by B(OH)3 without
      irreversible polyhistidine-RG-II complexation. Likewise, partially purified
      spinach extensins (histidine/lysine-rich cationic glycoproteins), strongly
      promoted RG-II dimerization by B(OH)3 in vitro. Thus certain polycations,
      including polyhistidine and wall glycoproteins, can chaperone RG-II, manoeuvring
      this polyanionic polysaccharide domain such that boron-bridging is favoured.
      These chaperones dissociate from RG-II after facilitating its dimerization,
      indicating that they act catalytically rather than stoichiometrically. We propose
      a natural role for extensin-RG-II interaction in steering cell-wall assembly.

PMID- 26301522
TI  - Comparison of techniques used to deliver a deeply impacted fetal head at full
      dilation: a systematic review and meta-analysis.
AB  - BACKGROUND: Second-stage caesarean section with a deeply impacted fetal head is
      associated with maternal and neonatal complications. OBJECTIVES: Systematic
      review and meta-analysis to identify, appraise and synthesise existing evidence
      that evaluated various techniques of delivering a baby with a deeply impacted
      head at full-dilation caesarean section. The primary outcome was uterine
      extension and secondary outcomes were other maternal and neonatal morbidities.
      SEARCH STRATEGY: Online searches of MEDLINE (1946-January 2015), EMBASE (1950
      January 2015), Web of Sciences (1950-2015), and the Cochrane Library databases
      were performed using a set of relevant keywords. SELECTION CRITERIA: All studies
      that compared the outcome of various techniques of delivering the baby's head at
      full-dilation caesarean section. DATA COLLECTION AND ANALYSIS: Methodological
      quality was assessed using the Newcastle-Ottawa scale. Data collected from each
      of the studies included variables on the participants, comparisons used, and feto
      maternal outcomes. Meta-analysis was performed using review manager 5.3. MAIN
      RESULTS: In total, 12 studies were included. Six studies (n = 455) examined
      primary outcomes. Meta-analysis showed that the risks of uterine incision
      extension, infection, mean blood loss, and operative time were significantly
      higher with the push technique compared with the reverse breech extraction. The
      evidence to support the Patwardhan method and fetal pillow was inadequate.
      AUTHORS' CONCLUSIONS: Evidence gathered from observational studies suggests that
      reverse breech extraction is associated with significantly lower maternal risks
      compared with the push method. TWEETABLE ABSTRACT: Meta-analysis suggests reverse
      breech extraction during caesarean section to deliver impacted fetus is safer.

PMID- 26301523
TI  - Inter-microcarrier transfer and phenotypic stability of stem cell-derived Schwann
      cells in stirred suspension bioreactor culture.
AB  - Emerging bioreactor technologies offer an effective way for scaled-up production
      of large numbers of cells for cell therapy applications. One of the clinical
      paradigms where cell therapy can be an asset is restorative neurosciences. Nerve
      repair can benefit from the injections of stem cells and/or Schwann cells, acting
      as a source for axon myelination, myelin debris clearance, and trophic support.
      We have adapted microcarrier-based suspension bioreactor culture for Schwann
      cells (SCs) differentiated from a new stem cell source - skin-derived precursors
      (SKPs). SKP-derived SCs attach and grow on different types of microcarriers in
      both static and stirred culture, with Cytodex 3 and CultiSpher-S found most
      effective. Inter-microcarrier migration of SKP-SCs represents a key mechanism for
      rapid expansion and colonization in stirred suspension culture. We have shown
      that microcarrier-expanded SKP-SCs cells express Schwann cell markers p75-NTR,
      GFAP and S100 and retain their key ability to myelinate axons both in vitro and
      in vivo. Scaled-up microcarrier-based production of SKP-SCs in suspension
      bioreactors appears feasible for timely generation of sufficient cell numbers for
      nerve repair strategies.

PMID- 26301524
TI  - Diversity in Graduate Medical Education in the United States by Race, Ethnicity,
      and Sex, 2012.

PMID- 26301525
TI  - Analytical challenges for measuring steroid responses to stress,
      neurodegeneration and injury in the central nervous system.
AB  - Levels of steroids in the adult central nervous system (CNS) show marked changes
      in response to stress, degenerative disorders and injury. However, their analysis
      in complex matrices such as fatty brain and spinal cord tissues, and even in
      plasma, requires accurate and precise analytical methods. Radioimmunoassays (RIA)
      and enzyme-linked immunosorbent assays, even with prepurification steps, do not
      provide sufficient specificity, and they are at the origin of many inconsistent
      results in the literature. The analysis of steroids by mass spectrometric methods
      has become the gold standard for accurate and sensitive steroid analysis.
      However, these technologies involve multiple purification steps prone to errors,
      and they only provide accurate reference values when combined with careful sample
      workup. In addition, the interpretation of changes in CNS steroid levels is not
      an easy task because of their multiple sources: the endocrine glands and the
      local synthesis by neural cells. In the CNS, decreased steroid levels may reflect
      alterations of their biosynthesis, as observed in the case of chronic stress,
      post-traumatic stress disorders or depressive episodes. In such cases, return to
      normalization by administering exogenous hormones or by stimulating their
      endogenous production may have beneficial effects. On the other hand, increases
      in CNS steroids in response to acute stress, degenerative processes or injury may
      be part of endogenous protective or rescue programs, contributing to the
      resistance of neural cells to stress and insults. The aim of this review is to
      encourage a more critical reading of the literature reporting steroid measures,
      and to draw attention to the absolute need for well-validated methods. We discuss
      reported findings concerning changing steroid levels in the nervous system by
      insisting on methodological issues. An important message is that even recent mass
      spectrometric methods have their limits, and they only become reliable tools if
      combined with careful sample preparation. 

PMID- 26301527
TI  - The cognitive science of fiction.
AB  - Fiction might be dismissed as observations that lack reliability and validity,
      but this would be a misunderstanding. Works of fiction are simulations that run
      on minds. They were the first kinds of simulation. All art has a metaphorical
      quality: a painting can be both pigments on canvas and a person. In literary art,
      this quality extends to readers who can be both themselves and, by empathetic
      processes within a simulation, also literary characters. On the basis of this
      hypothesis, it was found that the more fiction people read the better were their
      skills of empathy and theory-of-mind; the inference from several studies is that
      reading fiction improves social skills. In functional magnetic resonance imaging
      meta-analyses, brain areas concerned with understanding narrative stories were
      found to overlap with those concerned with theory-of-mind. In an orthogonal
      effect, reading artistic literature was found to enable people to change their
      personality by small increments, not by a writer's persuasion, but in their own
      way. This effect was due to artistic merit of a text, irrespective of whether it
      was fiction or non-fiction. An empirically based conception of literary art might
      be carefully constructed verbal material that enables self-directed personal
      change. WIREs Cogn Sci 2012, 3:425-430. doi: 10.1002/wcs.1185 For further
      resources related to this article, please visit the WIREs website. 

PMID- 26301526
TI  - Animal derived surfactant extract versus protein free synthetic surfactant for
      the prevention and treatment of respiratory distress syndrome.
AB  - BACKGROUND: A wide variety of surfactant preparations have been developed and
      tested including synthetic surfactants and surfactants derived from animal
      sources. Although clinical trials have demonstrated that both synthetic
      surfactant and animal derived surfactant preparations are effective, comparison
      in animal models has suggested that there may be greater efficacy of animal
      derived surfactant products, perhaps due to the protein content of animal derived
      surfactant. OBJECTIVES: To compare the effect of animal derived surfactant to
      protein free synthetic surfactant preparations in preterm infants at risk for or
      having respiratory distress syndrome (RDS). SEARCH METHODS: Searches were updated
      of the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane
      Library (2014), PubMed, CINAHL and EMBASE (1975 through November 2014). All
      languages were included. SELECTION CRITERIA: Randomized controlled trials
      comparing administration of protein free synthetic surfactants to administration
      of animal derived surfactant extracts in preterm infants at risk for or having
      respiratory distress syndrome were considered for this review. DATA COLLECTION
      AND ANALYSIS: Data collection and analysis were conducted according to the
      standards of the Cochrane Neonatal Review Group. MAIN RESULTS: Fifteen trials met
      the inclusion criteria. The meta-analysis showed that the use of animal derived
      surfactant rather than protein free synthetic surfactant resulted in a
      significant reduction in the risk of pneumothorax [typical relative risk (RR)
      0.65, 95% CI 0.55 to 0.77; typical risk difference (RD) -0.04, 95% CI -0.06 to 
      0.02; number needed to treat to benefit (NNTB) 25; 11 studies, 5356 infants] and
      a marginal reduction in the risk of mortality (typical RR 0.89, 95% CI 0.79 to
      0.99; typical RD -0.02, 95% CI -0.04 to -0.00; NNTB 50; 13 studies, 5413
      infants).Animal derived surfactant was associated with an increase in the risk of
      necrotizing enterocolitis [typical RR 1.38, 95% CI 1.08 to 1.76; typical RD 0.02,
      95% CI 0.01 to 0.04; number needed to treat to harm (NNTH) 50; 8 studies, 3462
      infants] and a marginal increase in the risk of any intraventricular hemorrhage
      (typical RR 1.07, 95% CI 0.99 to 1.15; typical RD 0.02, 95% CI 0.00 to 0.05; 10
      studies, 5045 infants) but no increase in Grade 3 to 4 intraventricular
      hemorrhage (typical RR 1.08, 95% CI 0.91 to 1.27; typical RD 0.01, 95% CI -0.01
      to 0.03; 9 studies, 4241 infants).The meta-analyses supported a marginal decrease
      in the risk of bronchopulmonary dysplasia or mortality associated with the use of
      animal derived surfactant preparations (typical RR 0.95, 95% CI 0.91 to 1.00;
      typical RD -0.03, 95% CI -0.06 to 0.00; 6 studies, 3811 infants). No other
      relevant differences in outcomes were noted. AUTHORS' CONCLUSIONS: Both animal
      derived surfactant extracts and protein free synthetic surfactant extracts are
      effective in the treatment and prevention of respiratory distress syndrome.
      Comparative trials demonstrate greater early improvement in the requirement for
      ventilator support, fewer pneumothoraces, and fewer deaths associated with animal
      derived surfactant extract treatment. Animal derived surfactant may be associated
      with an increase in necrotizing enterocolitis and intraventricular hemorrhage,
      though the more serious hemorrhages (Grade 3 and 4) are not increased. Despite
      these concerns, animal derived surfactant extracts would seem to be the more
      desirable choice when compared to currently available protein free synthetic
      surfactants.

PMID- 26301528
TI  - Unified theories of cognition.
AB  - Unified theories of cognition (UTCs) offer an alternative to the modal 'divide
      and conquer' methodology within cognitive science and attempt to address the full
      range of cognitive activity within a single theoretical framework. These
      theories, also termed 'cognitive architectures' are generally computational in
      nature and are intended to model, at some degree of fidelity, human cognition in
      a broad range of tasks. This style of research has numerous advantages, not the
      least of which being that the actual human cognitive system is itself an
      integrated system and many important tasks require bringing integrated
      capabilities to bear. There are also drawbacks, particularly dealing with the
      incompleteness of the knowledge base in cognitive science and the difficulty of
      evaluating such theories. Three architectures are profiled, each one representing
      a different 'home' discipline: from AI, Soar; from cognitive psychology, Adaptive
      Control of Thought-Rational; and from neuroscience, Leabra. Future directions for
      UTCs include expansion into branches of cognition not already well represented,
      such as spatial cognition, and increasing attention to cognitive moderators such
      as emotion and fatigue. Overall, this is a powerful research strategy that is
      likely to remain an important part of cognitive science for the foreseeable
      future. WIREs Cogn Sci 2012, 3:431-438. doi: 10.1002/wcs.1180 For further
      resources related to this article, please visit the WIREs website. 

PMID- 26301529
TI  - Free will and responsibility.
AB  - Free will is a set of capacities for conscious choice and control of actions and
      is essential for moral responsibility. While determinism is traditionally
      discussed as the main potential challenge to free will and responsibility, other
      potential challenges exist and need to be considered by philosophers and
      scientists. The cognitive sciences are relevant to free will both to study how
      people understand free will and potential challenges to it, and to study whether
      these challenges are supported by relevant scientific evidence. WIREs Cogn Sci
      2012, 3:439-449. doi: 10.1002/wcs.1181 For further resources related to this
      article, please visit the WIREs website. 

PMID- 26301530
TI  - Are groups more rational than individuals? A review of interactive decision
      making in groups.
AB  - Many decisions are interactive; the outcome of one party depends not only on its
      decisions or on acts of nature but also on the decisions of others. Standard game
      theory assumes that individuals are rational, self-interested decision makers
      that is, decision makers are selfish, perfect calculators, and flawless executors
      of their strategies. A myriad of studies shows that these assumptions are
      problematic, at least when examining decisions made by individuals. In this
      article, we review the literature of the last 25 years on decision making by
      groups. Researchers have compared the strategic behavior of groups and
      individuals in many games: prisoner's dilemma, dictator, ultimatum, trust,
      centipede and principal-agent games, among others. Our review suggests that
      results are quite consistent in revealing that group decisions are closer to the
      game-theoretic assumption of rationality than individual decisions. Given that
      many real-world decisions are made by groups, it is possible to argue that
      standard game theory is a better descriptive model than previously believed by
      experimental researchers. We conclude by discussing future research avenues in
      this area. WIREs Cogn Sci 2012, 3:471-482. doi: 10.1002/wcs.1184 For further
      resources related to this article, please visit the WIREs website. 

PMID- 26301531
TI  - Language and music: sound, structure, and meaning.
AB  - Language and music are the most impressive examples of humans' capacity to
      process complex sound and structure. Though interest in the relationship between
      these two abilities has a long history, only recently has cognitive and
      neuroscientific research started to illuminate both what is shared and what is
      distinct between linguistic and musical processing. This review considers
      evidence for a link between language and music at three levels of analysis:
      sound, structure, and meaning. These links not only inform our understanding of
      language and music, but also add to a more basic understanding of our processing
      of complex auditory stimuli, structure, meaning, and emotion. WIREs Cogn Sci
      2012, 3:483-492. doi: 10.1002/wcs.1186 For further resources related to this
      article, please visit the WIREs website. 

PMID- 26301533
TI  - Production of scandium-44 m and scandium-44 g with deuterons on calcium-44: cross
      section measurements and production yield calculations.
AB  - HIGHLIGHTS * Production of Sc-44 m, Sc-44 g and contaminants. * Experimental
      values determined using the stacked-foil technique. * Thick-Target production
      Yield (TTY) calculations. * Comparison with the TALYS code version 1.6.Among the
      large number of radionuclides of medical interest, Sc-44 is promising for PET
      imaging. Either the ground-state Sc-44 g or the metastable-state Sc-44 m can be
      used for such applications, depending on the molecule used as vector. This study
      compares the production rates of both Sc-44 states, when protons or deuterons are
      used as projectiles on an enriched Calcium-44 target. This work presents the
      first set of data for the deuteron route. The results are compared with the TALYS
      code. The Thick-Target production Yields of Sc-44 m and Sc-44 g are calculated
      and compared with those for the proton route for three different scenarios: the
      production of Sc-44 g for conventional PET imaging, its production for the new 3
      gamma imaging technique developed at the SUBATECH laboratory and the production
      of a Sc-44 m/Sc-44 g in vivo generator for antibody labelling.

PMID- 26301534
TI  - Investigation of the antifibrillatory drug interactions between Amiodarone and
      Ibutilide in isolated, perfused Rabbit hearts.
AB  - In view of the reliability of the serial-shock method of measuring ventricular
      fibrillation threshold (VFT) in quantitatively assessing the antifibrillatory
      potency of many anti-arrhythmic drugs and the alarming reports of the
      proarrhythmic effects of several anti-arrhythmic agents, it was decided to use
      the above technique to study the possible interactions that may occur when anti
      arrhythmic drugs from different classes are combined. Hearts isolated from New
      Zealand white rabbits of either sex weighing 1.5-2 kg were perfused by the
      Langendorff method with McEwen's solution. In six hearts, measurement of VFT was
      made in the absence of any drug throughout the experiments. Perfusion with either
      amiodarone or ibutilide produced significant, dose-dependent increase in VFT. In
      addition, there was no significant difference in the increase in VFT produced by
      the combined infusion of 1 MUmol of amiodarone and 0.01 MUmol of ibutilide and
      the summation of the increases produced by the separate infusion of these two
      concentrations. This is in contrast to a significant synergistic antifibrillatory
      effect of the combined use of lidocaine and propranolol that was reported
      previously. The lack of antifibrillatory interactions between amiodarone and
      Ibutilide may suggest the safety of combining the two drugs in the treatment of
      cardiac arrhythmias. However, further studies are required to establish this in
      the clinical setup. 

PMID- 26301535
TI  - Risk Factors for Mortality and Endotracheal Intubation after Methadone
      Intoxication.
AB  - This was a retrospective chart review to evaluate various risk factors associated
      with in-hospital mortality and intubation risk in acute methadone overdose. All
      patients admitted to an academic hospital in Tehran, Iran, during a 10-year
      period (2000-2009) constituted the study sample. Exclusion criteria were
      significant comorbidities and age under 18 years. Outcome variables were in
      hospital mortality and being intubated during admission. A total of 802 patients
      were enrolled in the study. There were 15 (1.8%) deaths due to methadone overdose
      or its complications. The number of yearly admissions was 15 patients in 2000, 16
      in 2001, 16 in 2002, 18 in 2003, 23 in 2004, 38 in 2005, 59 in 2006, 110 in 2007,
      206 in 2008 and 301 in 2009. Based on logistic regression analysis, the most
      important independent variable predicting mortality was length of admission in
      toxicology ward [OR (95% CI): 1.6 (1.1-2.3)]. For the prediction of intubation,
      independent variables were Glasgow Coma Scale (GCS) score of 5-9 [OR (95% CI):
      356.5 (9.8-12907.4)] in the emergency department (ED), miosis in the ED [356.9
      (1.4-87872.5)] and respiratory rate in the ED [1.5 (1.1-2.1)]. Linear regression
      model for length of hospitalization showed patient age as the most important
      variable for prediction of this outcome. Despite a relatively low mortality rate,
      the increasing number of methadone-poisoned patients requires special attention
      to this common intoxication. Careful disposition of patients from ED to ordinary
      wards or intensive care units and also from higher to lower levels of care should
      be considered in methadone overdose.

PMID- 26301536
TI  - "Perception of the speech code" revisited: Speech is alphabetic after all.
AB  - We revisit an article, "Perception of the Speech Code" (PSC), published in this
      journal 50 years ago (Liberman, Cooper, Shankweiler, & Studdert-Kennedy, 1967)
      and address one of its legacies concerning the status of phonetic segments, which
      persists in theories of speech today. In the perspective of PSC, segments both
      exist (in language as known) and do not exist (in articulation or the acoustic
      speech signal). Findings interpreted as showing that speech is not a sound
      alphabet, but, rather, phonemes are encoded in the signal, coupled with findings
      that listeners perceive articulation, led to the motor theory of speech
      perception, a highly controversial legacy of PSC. However, a second legacy, the
      paradoxical perspective on segments has been mostly unquestioned. We remove the
      paradox by offering an alternative supported by converging evidence that segments
      exist in language both as known and as used. We support the existence of segments
      in both language knowledge and in production by showing that phonetic segments
      are articulatory and dynamic and that coarticulation does not eliminate them. We
      show that segments leave an acoustic signature that listeners can track. This
      suggests that speech is well-adapted to public communication in facilitating, not
      creating a barrier to, exchange of language forms.

PMID- 26301537
TI  - The ADAPTABLE Trial and PCORnet: Shining Light on a New Research Paradigm.

PMID- 26301539
TI  - The investigation of excited state proton transfer mechanism in water-bridged 7
      azaindole.
AB  - Based on the time-dependent density functional theory (TDDFT), the excited-state
      intermolecular proton transfer (ESIPT) mechanism of water-bridged 7-azaindole has
      been investigated theoretically. The calculations of primary bond lengths and the
      IR vibrational spectra between the S0 state and the S1 state that verified the
      intramolecular hydrogen bond were strengthened. The fact that reproduced
      experimental absorbance and fluorescence emission spectra well theoretically
      demonstrate that the TDDFT theory we adopted is reasonable and effective. In
      addition, intramolecular charge transfer based on the frontier molecular orbitals
      demonstrated the indication of the ESIPT reaction. The constructed potential
      energy curves of ground state and the first excited state based on keeping the
      H2...O3 and H6...N7 distances fixed at a series of values have been used to
      illustrate the ESIPT process. A relative lower barrier of 5.94 kcal/mol in the S1
      state potential energy curve for type II (lower than that of 9.82 kcal/mol in the
      S1 state for type I) demonstrates that type II ESIPT process occurs firstly in
      7Al-2H2O complex.

PMID- 26301538
TI  - In Situ Formation of an Azo Bridge on Proteins Controllable by Visible Light.
AB  - Optical modulation of proteins provides superior spatiotemporal resolution for
      understanding biological processes, and photoswitches built on light-sensitive
      proteins have been significantly advancing neuronal and cellular studies. Small
      molecule photoswitches could complement protein-based switches by mitigating
      potential interference and affording high specificity for modulation sites.
      However, genetic encodability and responsiveness to nonultraviolet light, two
      desired properties possessed by protein photoswitches, are challenging to be
      engineered into small molecule photoswitches. Here we developed a small molecule
      photoswitch that can be genetically installed onto proteins in situ and
      controlled by visible light. A pentafluoro azobenzene-based photoswitchable click
      amino acid (F-PSCaa) was designed to isomerize in response to visible light.
      After genetic incorporation into proteins via the expansion of the genetic code,
      F-PSCaa reacts with a nearby cysteine within the protein generating an azo bridge
      in situ. The resultant bridge is switchable by visible light and allows
      conformation and binding of CaM to be regulated by such light. This photoswitch
      should prove valuable in optobiology for its minimal interference, site
      flexibility, genetic encodability, and response to the more biocompatible visible
      light. 

PMID- 26301540
TI  - Study of the decomposition pathway of 12-molybdophosphoric acid in aqueous
      solutions by micro Raman spectroscopy.
AB  - Micro Raman spectroscopy was applied to investigate the speciation of heteropoly
      and isopoly molybdates in 0.05 and 0.005 M aqueous solutions of 12
      molybdophosphoric acid at pH values between 1 and 6. For comparative purposes,
      (31)P NMR spectroscopy was applied too. It is shown that stability of Keggin
      anion is influenced both by pH and concentration of solution. The Keggin
      structure is stable in acidic solutions (pH<1.6) while defective Keggin
      structures are formed with further alkalization (up to pH5.6). Monolacunary anion
      PMo11O(39)(7-) is the main component in the pH region from 1.6 to 3.4. Further
      removal of molybdenyl species causes the appearance of other vacant Keggin
      structures such as PMo9O31(OH)(3)(6-) and PMo6O(25)(9-) at about pH4. At pH5.0,
      anion PMo6O(25)(9-) is the main species. In solutions with pH greater than 5.0,
      heteropolymolybdates disappear completely and isopolymolybdates Mo7O(24)(6-) and
      MoO(4)(2-) are formed in higher amounts. In more diluted solution of 0.005 M, the
      decomposition scheme of 12-molybdophosphoric acid solution with increasing of pH
      takes place without observation of significant amounts of Mo7O(24)(6-) species.
      If alkalinization is performed with 0.5 M instead of 5 M NaOH, there are no
      significant changes in the Raman spectra of solutions. It is shown that the
      spectra of evaporated samples may be used for the identification of molecular
      species in corresponding concentrated solutions. However, Raman spectra of dry
      residues of more diluted solutions differ from spectra of corresponding solutions
      due to the reactions performed during the process of drying and cannot be used
      for unambiguous identification of species in solution. Acidification of 0.05 M
      solution of Na2MoO4 shows that at pH>5.6, molybdate anion MoO(4)(2-) dominates,
      while in the pH range between 5.6 and 1, heptamolybdate anion Mo7O(24)(6-) is
      preferentially formed.

PMID- 26301541
TI  - Influence of CeO2 content on complex optical parameters of phosphovanadate glass
      system.
AB  - In the present work, glass system of the compositions of 60V2O5-5P2O5-(35-x)B2O3
      xCeO2 is prepared by modified melt-quenching method. The conformation of
      amorphous phase in sample was done through X-ray diffraction analysis. Optical
      studies were carried out at room temperature and direct and indirect band gap
      energy, refractive index, Urbach energy, molar refractivity and polarizability
      have been determined. The values of indirect band gap are lower than the
      corresponding values of direct band gap. Urbach energy is observed between 0.58
      and 0.48 eV. The samples show gradual increase in absorption around the 225 nm,
      which results in increase of refractive index and optical conductivity. The real
      and imaginary dielectric constants show good agreement with each other.

PMID- 26301542
TI  - Elemental analysis-aided Raman spectroscopic studies on Chinese cloisonne wares
      and painted enamels from the Imperial Palace.
AB  - Two kinds of enamels, including Chinese cloisonne wares from Fuwang chamber and
      gourd-shaped painted enamels decorations from the Forbidden City, in the Imperial
      Palace of China, are investigated by micro-Raman spectroscopy in combination with
      laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and
      energy-dispersive X-ray fluorescence (EDXRF) in order to examine and analyze the
      composition of the glaze layer in each case. In this study the excitation is
      employed with either a NIR laser (785 nm) or a red laser (632.8 nm) in order to
      effectively eliminate the interference of background fluorescence and resonance
      effect. We have identified that the major matrix ingredients of the cloisonne
      wares are lead-based potash-lime silicate glasses while lead-potash silicate
      glass matrix is the main constituent for the painted enamels. Eight different
      colored areas of glaze layer also have been discussed in detail due to the
      distinct colors including turquoise, deep blue, yellow, white, red, pink, deep
      green and pale green. Their identification based on Raman data will be useful
      with regard to rapid and on site analysis and the restoration of the enamel
      decorations.

PMID- 26301543
TI  - Structural, spectral and magnetic studies of two Co(II)-N-heterocyclic
      diphosphonates based on multinuclear units.
AB  - Two examples of Co(II)-N-heterocyclic coordination polymers based on 1
      hydroxyethylidenediphosphonic acid (H5L=CH3C(OH)(PO3H2)2), namely
      0.5(H3NCH2CH2NH3).[Co6(Cl2)(H3L)2(H2L)(HL)(2,2'-bipy)6] 1 and
      2(NH4).[Co3(HL)2(H2O)2(phen)2].2(H2O) 2, have been solvothermally obtained by
      introducing the second ligands 2,2'-bipyridine/1,10-phenanthroline (2,2'
      bipy/phen) and characterized by powder X-ray diffraction (PXRD), elemental
      analysis, IR, TG-DSC. The single-crystal X-ray diffractions show that compound 1
      possesses a 0-D structure with hexa-nuclear cluster [Co6(O-P-O)8] built through
      single/double O-P-O bridges and compound 2 displays a 1-D ladder-like chain
      structure with magnetic topology building blocks [Co4(O-P-O)4]n. Then H-bonding
      and pi-pi stacking interactions further expand the two low-dimensional structures
      into three-dimensional supramolecular frameworks. Fluorescent measurements reveal
      that both the maximum emission peaks of 1-2 are centered at 423nm, mainly
      deriving from intraligand pi*-pi transition state of N-heterocyclic ligand 2,2'
      bipy/phen, respectively. Magnetism data indicate that 1 exhibits
      antiferromagnetic behavior within hexa-nuclear Co(II) clusters, while 2 shows
      weak ferromagnetic interactions in 1-D topology Co(II)-chain, showing promising
      potential as magnetic materials. 

PMID- 26301544
TI  - Permafrost collapse alters soil carbon stocks, respiration, CH4 , and N2O in
      upland tundra.
AB  - Release of greenhouse gases from thawing permafrost is potentially the largest
      terrestrial feedback to climate change and one of the most likely to occur;
      however, estimates of its strength vary by a factor of thirty. Some of this
      uncertainty stems from abrupt thaw processes known as thermokarst (permafrost
      collapse due to ground ice melt), which alter controls on carbon and nitrogen
      cycling and expose organic matter from meters below the surface. Thermokarst may
      affect 20-50% of tundra uplands by the end of the century; however, little is
      known about the effect of different thermokarst morphologies on carbon and
      nitrogen release. We measured soil organic matter displacement, ecosystem
      respiration, and soil gas concentrations at 26 upland thermokarst features on the
      North Slope of Alaska. Features included the three most common upland thermokarst
      morphologies: active-layer detachment slides, thermo-erosion gullies, and
      retrogressive thaw slumps. We found that thermokarst morphology interacted with
      landscape parameters to determine both the initial displacement of organic matter
      and subsequent carbon and nitrogen cycling. The large proportion of ecosystem
      carbon exported off-site by slumps and slides resulted in decreased ecosystem
      respiration postfailure, while gullies removed a smaller portion of ecosystem
      carbon but strongly increased respiration and N2 O concentration. Elevated N2 O
      in gully soils persisted through most of the growing season, indicating sustained
      nitrification and denitrification in disturbed soils, representing a potential
      noncarbon permafrost climate feedback. While upland thermokarst formation did not
      substantially alter redox conditions within features, it redistributed organic
      matter into both oxic and anoxic environments. Across morphologies, residual
      organic matter cover, and predisturbance respiration explained 83% of the
      variation in respiration response. Consistent differences between upland
      thermokarst types may contribute to the incorporation of this nonlinear process
      into projections of carbon and nitrogen release from degrading permafrost. 

PMID- 26301545
TI  - Enantioselective Organocatalytic Transfer Hydrogenation of 1,2-Dihydroquinoline
      through Formation of Aza-o-xylylene.
AB  - A new way of forming the aza-o-xylylene with easily accessible 1,2
      dihydroquinolines as precursor has been developed. The presence of an electron
      donating group at the proper position of 1,2-dihydroquinoline was crucial for
      protonation of the alkene through dearomatization with a simple Bronsted acid.
      The in situ forming reactive intermediate was trapped with Hantzsch ester to
      afford tetrahydroquinolines in excellent yield and enantioselectivity. 

PMID- 26301546
TI  - Boundary Spanning Leadership Practices for Population Health.
AB  - This department highlights change management strategies that may be successful in
      strategically planning and executing organizational change initiatives. In this
      article, the authors discuss boundary spanning leadership practices for achieving
      the Triple Aim of simultaneously improving the health of populations, improving
      the patient experience, and reducing per-capita cost of health care. Drawing on
      experience with an existing population-focused heart failure clinic borne of an
      academic-practice partnership, the authors discuss boundary spanning leadership
      practices aimed at achieving the Triple Aim concept and its intended design. 

PMID- 26301547
TI  - Residency and Fellowship Programs for RNs and Advanced Practice RNs.
AB  - In this month's column, the Senior Accreditation Operations Manager of the
      American Nurses Credentialing Center (ANCC) discusses the value of nursing
      residency programs and current discussion in the profession, along with criteria
      offered by the ANCC to support this imperative for both RNs and advanced practice
      RNs including new graduates and those transitioning between clinical settings. 

PMID- 26301549
TI  - The Influence of Emerging Nursing Strategy and Policy Leaders: An Interview With
      Dr Suzanne Miyamoto.
AB  - This department highlights emerging nursing leaders who have demonstrated great
      potential in advancing innovation and patient care leadership in practice,
      policy, research, education, and theory. This interview profiles Suzanne
      Miyamoto, PhD, RN, Senior Director of Government Affairs and Health Policy at the
      American Association of Colleges of Nursing. 

PMID- 26301548
TI  - Designing Tomorrow: Rewriting the Nurse Executive Script for an Emerging Stage.
AB  - As nurse executives (NEs), we are aware of our emerging, expanding roles as
      single settings, whether hospitals, clinics, or other entities, are morphing into
      components of whole systems. We are challenged to focus appropriate attention
      inward to ensure that nursing is positioned to lead while extending ourselves
      outward, to participate in shaping new systems. This month, we will shine the
      spotlight on these transitions, identifying some of the triumphs and challenges,
      in a conversation with Donna King, an NE with Advocate Health Care in Illinois. 

PMID- 26301550
TI  - Linking Unit Collaboration and Nursing Leadership to Nurse Outcomes and Quality
      of Care.
AB  - OBJECTIVE: The objective of this study is to identify the effects of unit
      collaboration and nursing leadership on nurse outcomes and quality of care.
      BACKGROUND: Along with the current healthcare reform, collaboration of care
      providers and nursing leadership has been underscored; however, empirical
      evidence of the impact on outcomes and quality of care has been limited. METHODS:
      Data from 29742 nurses in 1228 units of 200 acute care hospitals in 41 states
      were analyzed using multilevel linear regressions. Collaboration (nurse-nurse
      collaboration and nurse-physician collaboration) and nursing leadership were
      measured at the unit level. Outcomes included nurse job satisfaction, intent to
      leave, and nurse-reported quality of care. RESULTS: Nurses reported lower intent
      to leave, higher job satisfaction, and better quality of care in units with
      better collaboration and stronger nursing leadership. CONCLUSION: Creating a care
      environment of strong collaboration among care providers and nursing leadership
      can help hospitals maintain a competitive nursing workforce supporting high
      quality of care.

PMID- 26301551
TI  - Achieving 80% BSN by 2020: Lessons Learned From Kentucky's Registered Nurses.
AB  - OBJECTIVE: The aim of this study was to understand the educational status and
      plans of Kentucky's RN workforce in advancing nursing educational levels.
      BACKGROUND: The Institute of Medicine called for 80% of nurses to hold a minimum
      of a BSN by 2020. Nurse leaders from practice, academe, and the community need
      evidence to guide the development of effective strategies. METHODS: An electronic
      survey was administered to Kentucky's RNs. This descriptive analysis was based on
      1363 usable responses. RESULTS: Only 40% of Kentucky's RNs held at least a BSN.
      Another 17% were enrolled in a nursing degree program; half of those enrolled
      were pursuing a BSN. Of those not enrolled in a degree program, 61.5% reported no
      plans to return to school. The top barriers were lack of perceived benefit,
      financial concerns, family obligations, and planned retirement. The top
      motivating factor was career advancement. CONCLUSION: The gap between the current
      reality and the goal is wide. Nurse leaders will need to develop creative
      strategies that strengthen motivating factors and reduce barriers to accelerate
      movement toward increasing BSN rates.

PMID- 26301552
TI  - Managerial and Organizational Discourses of Workplace Bullying.
AB  - OBJECTIVE: To explore how workplace bullying is addressed by hospital nursing
      unit managers and organizational policies. BACKGROUND: Although workplace
      bullying is costly to organizations, nurses report that managers do not
      consistently address the issue. METHODS: This study used discourse analysis to
      analyze interview data and policy documents. RESULTS: There were differences in
      the manner in which managers and the policy documents labeled bullying-type
      behaviors and discussed the roles and responsibilities of staff and managers.
      Policies did not clearly delineate how managers should respond to workplace
      bullying. CONCLUSIONS: These differences can allow management variation, not
      sanctioned by policy. Unclear policy language can also offer insufficient
      guidance to managers, resulting in differential enforcement of policies.

PMID- 26301553
TI  - Multistate Approach to Preparing Registered Nurses: How 3 Nurse Executives Shaped
      a New Nursing Education Model.
AB  - A new model for educating baccalaureate nurses emerged from the needs of
      employers and came to fruition through a unique partnership resulting in the
      development of the 1st competency-based, asynchronous single-curriculum
      prelicensure program in the United States. Three nurse executives championed the
      design and implementation of the multistate approach to preparing RNs (MAP RN)
      program. The nationally accredited program has been initiated in 5 states. 

PMID- 26301554
TI  - Recent developments in steroidal and nonsteroidal aromatase inhibitors for the
      chemoprevention of estrogen-dependent breast cancer.
AB  - Aromatase, a cytochrome P450 enzyme complex present in breast tissues, plays a
      significant role in the biosynthesis of important endogenous estrogens from
      androgens. The source of estrogen production in breast cancer tissues is intra
      tumoral aromatase, and inhibition of aromatase may inhibit the growth stimulation
      effect of estrogens in breast cancer tissues. Consequently, aromatase is
      considered a useful therapeutic target in the treatment and prevention of
      estrogen-dependent breast cancer. Recently, different natural products and
      synthetic compounds have been rapidly developed, studied, and evaluated for
      aromatase inhibitory activity. Aromatase inhibitors are classified into two
      categories on the basis of their chemical structures, i.e., steroidal and
      nonsteroidal aromatase inhibitors. This review highlights the synthetic steroidal
      and nonsteroidal aromatase inhibitors reported in the literature in the last few
      years and will aid medicinal chemists in the design and synthesis of novel and
      pharmacologically-potent aromatase inhibitors for the treatment of breast cancer.

PMID- 26301555
TI  - Synthesis and in-vitro evaluation of 2-amino-4-arylthiazole as inhibitor of 3D
      polymerase against foot-and-mouth disease (FMD).
AB  - Foot-and-mouth disease (FMD) is a highly contagious vesicular disease of
      livestock caused by a highly variable RNA virus, foot-and-mouth disease virus
      (FMDV). One of the targets to suppress expansion of and to control FMD is 3D
      polymerase (FMDV 3Dpol). In this study, 2-amino-4-arylthiazole derivatives were
      synthesized and evaluated for their inhibitory activity against FMDV 3Dpol. Among
      them, compound 20i exhibited the most potent functional inhibition (IC50 = 0.39
      MUM) of FMDV 3D polymerase and compound 24a (EC50 = 13.09 MUM) showed more potent
      antiviral activity than ribavirin (EC50 = 1367 MUM) and T1105 (EC50 = 347 MUM)
      with IBRS-2 cells infected by the FMDV O/SKR/2010 strain.

PMID- 26301556
TI  - In vivo evaluation of isolated triterpenes and semi-synthetic derivatives as
      antimalarial agents.
AB  - The triterpenes balsaminoside B (1) and karavilagenin C (2) were isolated from
      the African medicinal plant Momordica balsamina L. Karavoates B (3) and D (4)
      were synthesized by diacylation of 2 with acetic and propionic anhydrides,
      respectively. In previous work, derivatives 3 and 4 exhibited submicromolar
      median inhibitory concentrations (IC50) in vitro against Plasmodium falciparum
      Welch (human malaria parasite) strains 20 to 25 times lower than those of natural
      product 2. The main objective of the present study was to explore structure-in
      vivo antimalarial activity relationships (SAR) for compounds 1-4 in Plasmodium
      berghei Vincke and Lips NK65-infected mice in the 4 day suppressive test. Semi
      synthetic derivatives 3 and 4 exhibited greater in vivo antimalarial activity
      than isolates 1 and 2. Orally and subcutaneously administered karavoate B
      exhibited the greatest in vivo antimalarial activity (55.2-58.1% maximal
      suppression of parasitemia at doses of 50 mg kg(-1) day(-1)). Diacylation of
      natural isolate 2 with short chain carboxylic acid moieties yielded derivatives
      with enhanced maximal in vivo parasitemia suppression for both routes of
      administration. Maximal in vivo parasite suppression by diacetyl derivative 3 was
      roughly double that of natural precursor 2.

PMID- 26301557
TI  - Synthesis of new indole-based bisphosphonates and evaluation of their chelating
      ability in PE/CA-PJ15 cells.
AB  - Bisphosphonates are the most important class of antiresorptive agents used
      against osteoclast-mediated bone loss, and, more recently, in oncology. These
      compounds have high affinity for calcium ions (Ca(2+)) and therefore target bone
      mineral, where they appear to be internalized selectively by bone-resorbing
      osteoclasts and inhibit osteoclast function. They are extensively used in
      healthcare, however they are affected by severe side effects; pharmacological
      properties of bisphosphonates depend on their molecular structure, which is
      frequently the cause of poor intestinal adsorption and low distribution. In this
      work we synthesized six novel bisphosphonate compounds having a variably
      substituted indole moiety to evaluate their extra- and intracellular calcium
      chelating ability in PE/CA-PJ15 cells. Preliminary in silico and in vitro ADME
      studies were also performed and the results suggested that the indole moiety
      plays an important role in cell permeability and metabolism properties.

PMID- 26301558
TI  - Spirooxindole-derived morpholine-fused-1,2,3-triazoles: Design, synthesis,
      cytotoxicity and apoptosis inducing studies.
AB  - A series of new spirooxindole-derived morpholine-fused-1,2,3-triazole derivatives
      has been synthesized from isatin spiro-epoxides. The protocol involves
      regiospecific isatin-epoxide ring opening with azide nucleophile followed by
      sequential O-propargylation, and intramolecular 1,3-dipolar cycloaddition
      reaction. These compounds have been evaluated for their antiproliferative
      activity against selected human tumor cell lines of lung (A549), breast (MCF-7),
      cervical (HeLa), and prostate (DU-145). Among the tested compounds, 6i, 6n and 6p
      showed potent growth inhibition against A549 cell line with IC50 values in the
      range of 1.87-4.36 MUM, which are comparable to reference standards doxorubicin
      and 5-flourouracil. The compounds 6i and 6p treated A549 cells displayed typical
      apoptotic morphological features such as cell shrinkage, nuclear condensation,
      fragmentation, and decreased migration potential. Flow-cytometry analysis
      revealed that the compounds arrested the cells in G2/M phase of cell cycle.
      Hoechst and acridine orange/ethidium bromide staining studies also showed that
      the cell proliferation was inhibited through induction of apoptosis. Moreover,
      the compounds treatment led to collapse of the mitochondrial membrane potential
      (DPsim) and increased levels of reactive oxygen species (ROS) were noted in A549
      cells.

PMID- 26301559
TI  - Exploration of the molecular architecture of the orthosteric binding site in the
      alpha4beta2 nicotinic acetylcholine receptor with analogs of 3
      (dimethylamino)butyl dimethylcarbamate (DMABC) and 1-(pyridin-3-yl)-1,4
      diazepane.
AB  - X-ray crystal structures of acetylcholine binding proteins (AChBPs) have revealed
      two different possible extensions to the classical ligand binding pocket known to
      accommodate various nicotinic agonists. One of the pockets is limited in size
      while the other is of considerable dimensions and protrudes along the interfacial
      cleft between subunits. To probe these putative extensions in functional
      nicotinic acetylcholine receptors (nAChRs), elongated analogs of 3
      (dimethylamino)butyl dimethylcarbamate (DMABC) and 1-(pyridine-3-yl)-1,4
      diazepane were prepared and characterized pharmacologically at neuronal
      heteromeric nAChRs. Although the new analogs, relative to parent compounds,
      displayed lower binding affinities, functional characterization of selected
      compounds revealed that they had retained partial alpha4beta2 nAChR agonist
      activity. The structure-activity relationship data did not indicate an upper
      limit to the size of substituents as would have been expected if the ligand was
      bound in the smaller pocket. The data were better in agreement with a binding
      mode in which substituents protrude along the interfacial cleft of the receptor.
      This was further supported by docking into a homology model of the alpha4-beta2
      nAChR interface and by surface plasmon resonance biosensor analysis of binding of
      the compounds to acetylcholine-binding proteins, where they exhibit preference
      for Lymnaea stagnalis ACh binding protein (Ls-AChBP) over the Aplysia california
      ACh binding protein (Ac-AChBP). These results suggest new opportunities for
      expanding chemical space in the development of partial agonist and may be of
      interest in relation to development of novel smoking cessation aids.

PMID- 26301560
TI  - Evaluation of the Safety and Efficacy of the Novel Svelte Acrobat Integrated
      Delivery System via Radial Approach With 5 Fr Catheters.
AB  - PURPOSE: To evaluate the safety and efficacy of the Svelte Acrobat integrated
      delivery system (IDS) via radial approach with 5 Fr catheters. The direct
      stenting (DS) system enables easy delivery, deployment, and postdilatation of a
      cobalt-chromium stent. METHODS: Patients with coronary artery disease (CAD) were
      prospectively enrolled at three centers to undergo percutaneous coronary
      intervention with DS via radial approach using 5 Fr catheters. The primary
      endpoint was IDS success, which was defined as DS without postdilatation and
      final stenosis <20% with Thrombolysis in Myocardial Infarction (TIMI)-3 flow.
      RESULTS: Fifty consecutive patients with 55 lesions were included. The procedure
      success rate was 98%. The device could not cross the lesion in 2 cases, so DS
      success was 96%. Fifty lesions met the primary study objective; thus, IDS success
      rate was 91%. The procedure duration was 21 +/- 9 minutes, fluoroscopy time was
      7.3 +/- 4.7 minutes, and contrast volume per vessel was 103 +/- 33 cm3. The final
      residual stenosis, by quantitative coronary angiography, was 3.4 +/- 4%. The
      reduced need for additional catheters resulted in a 20% procedural cost
      reduction. There were no bleeding or vascular complications. At 8 months, the
      event-free survival rate was 84%. CONCLUSIONS: DS using the Svelte Acrobat IDS
      via radial approach with low-profile catheters is safe and efficacious in select
      coronary artery disease patients, and its use is associated with potential
      procedural cost savings.

PMID- 26301561
TI  - The Impact and Pathophysiologic Consequences of Coronary Artery Calcium
      Deposition in Percutaneous Coronary Interventions.
AB  - The presence of coronary artery calcium is indicative of advanced coronary artery
      disease and is a predictor of clinical events including stroke, myocardial
      infarction, and cardiac arrest. Recognition of the risk factors and the clinical
      implications associated with coronary artery calcium is vital in identifying both
      preventative measures as well as treatment options. Non-invasive and invasive
      strategies can help quantify these calcified lesions and aid in appropriate
      patient selection for possible use of atheroablative devices. While mild to
      moderately calcified lesions can be predilated with balloon angioplasty, severely
      calcified vessels may be resistant to adequate predilatation and preclude stent
      delivery and optimal expansion, potentially increasing the risk of early and late
      complications. The use of atherectomy devices is an invaluable treatment option
      for these complex lesions, given the ability for plaque modification and changing
      the compliance of heavily calcified vessels, increasing procedural success rates.

PMID- 26301562
TI  - Percutaneous Pulmonary Balloon Valvuloplasty Provides Good Long-Term Outcomes in
      Adults With Pulmonary Valve Stenosis.
AB  - BACKGROUND: Percutaneous balloon pulmonary valvuloplasty (PBPV) is well described
      in children, but data on the efficacy and long-term outcomes in adult patients
      with pulmonary valve stenosis (PVS) are limited. OBJECTIVE: To estimate the long
      term outcomes of PBPV in adult PVS patients. METHODS: We performed a
      retrospective analysis of 41 consecutive adult cases (18 females, 23 males) with
      moderate to severe PVS who underwent PBPV at the First Affiliated Hospital of
      Soochow University between January 1999 and December 2005. Follow-up was
      available for all patients (mean follow-up of 11.3 +/- 2.1 years; range, 9-15
      years). RESULTS: Before intervention, the peak systolic gradient (PSG) was 71.3
      +/- 27.8 mm Hg. Immediately after intervention, the PSG was reduced to 30.9 +/-
      10.9 mm Hg (P<.001). At short-term, mid-term, and long-term follow-up, the mean
      echocardiographic PSGs were 30.6 +/- 11.9 mm Hg, 31.1 +/- 16.8 mm Hg, and 27.9 +/
      7.6 mm Hg, respectively (P<.001 compared with preintervention PSG). At the last
      follow-up, 37 of 41 patients (90.2%) had a PSG <36 mm Hg. Four patients (9.8%)
      underwent a second PBPV. Patients with immediate postintervention PSG >=36 mm Hg
      were more likely to need a second PBPV. Two cases with immediate postintervention
      PSG >=36 mm Hg experienced a spontaneous PSG reduction to <36 mm Hg. No serious
      adverse complications happened during or after the procedure. CONCLUSIONS: PBPV
      as a treatment for PVS was safe, and provided good long-term outcomes. Some
      patients with less-optimal immediate results may experience a spontaneous PSG
      reduction. A small proportion of patients required a second PBPV, especially
      those with poor immediate results. Close follow-up is necessary.

PMID- 26301563
TI  - Iterative Coupling of Two Different Enones by Nitromethane Using Bifunctional
      Thiourea Organocatalysts. Stereocontrolled Assembly of Cyclic and Acyclic
      Structures.
AB  - An organocatalytic iterative assembly line has been developed in which
      nitromethane was sequentially coupled with two different enones using a
      combination of pseudoenantiomeric cinchona-based thiourea catalysts. Application
      of unsaturated aldehydes and ketones in the second step of the iterative sequence
      allows the construction of cyclic syn-ketols and acyclic compounds with multiple
      contiguous stereocenters. The combination of the multifunctional substrates and
      ambident electrophiles rendered some organocatalytic transformations possible
      that have not yet been realized in bifunctional noncovalent organocatalysis. 

PMID- 26301564
TI  - Are beta-blockers on the therapeutic horizon for ovarian cancer treatment?

PMID- 26301567
TI  - Effects of microstructural inclusions on fatigue life of polyether ether ketone
      (PEEK).
AB  - In this study, the effects of microstructural inclusions on fatigue life of
      polyether ether ketone (PEEK) was investigated. Due to the versatility of its
      material properties, the semi-crystralline PEEK polymer has been increasingly
      adopted in a wide range of applications particularly as a biomaterial for
      orthopedic, trauma, and spinal implants. To obtain the cyclic behavior of PEEK,
      uniaxial fully-reversed strain-controlled fatigue tests were conducted at ambient
      temperature and at 0.02 mm/mm to 0.04 mm/mm strain amplitudes. The microstructure
      of PEEK was obtained using the optical and the scanning electron microscope (SEM)
      to determine the microstructural inclusion properties in PEEK specimen such as
      inclusion size, type, and nearest neighbor distance. SEM analysis was also
      conducted on the fracture surface of fatigue specimens to observe microstructural
      inclusions that served as the crack incubation sites. Based on the experimental
      strain-life results and the observed microstructure of fatigue specimens, a
      microstructure-sensitive fatigue model was used to predict the fatigue life of
      PEEK that includes both crack incubation and small crack growth regimes. Results
      show that the employed model is applicable to capture microstructural effects on
      fatigue behavior of PEEK.

PMID- 26301566
TI  - TCR affinity for thymoproteasome-dependent positively selecting peptides
      conditions antigen responsiveness in CD8(+) T cells.
AB  - In the thymus, low-affinity T cell antigen receptor (TCR) engagement facilitates
      positive selection of a useful T cell repertoire. Here we report that TCR
      responsiveness of mature CD8(+) T cells is fine tuned by their affinity for
      positively selecting peptides in the thymus and that optimal TCR responsiveness
      requires positive selection on major histocompatibility complex class I
      associated peptides produced by the thymoproteasome, which is specifically
      expressed in the thymic cortical epithelium. Thymoproteasome-independent positive
      selection of monoclonal CD8(+) T cells results in aberrant TCR responsiveness,
      homeostatic maintenance and immune responses to infection. These results
      demonstrate a novel aspect of positive selection, in which TCR affinity for
      positively selecting peptides produced by thymic epithelium determines the
      subsequent antigen responsiveness of mature CD8(+) T cells in the periphery. 

PMID- 26301565
TI  - Histone reader BRWD1 targets and restricts recombination to the Igk locus.
AB  - B lymphopoiesis requires that immunoglobulin genes be accessible to RAG1-RAG2
      recombinase. However, the RAG proteins bind widely to open chromatin, which
      suggests that additional mechanisms must restrict RAG-mediated DNA cleavage. Here
      we show that developmental downregulation of interleukin 7 (IL-7)-receptor
      signaling in small pre-B cells induced expression of the bromodomain-family
      member BRWD1, which was recruited to a specific epigenetic landscape at Igk
      dictated by pre-B cell receptor (pre-BCR)-dependent Erk activation. BRWD1
      enhanced RAG recruitment, increased gene accessibility and positioned nucleosomes
      5' to each Jkappa recombination signal sequence. BRWD1 thus targets recombination
      to Igk and places recombination within the context of signaling cascades that
      control B cell development. Our findings represent a paradigm in which, at any
      particular antigen-receptor locus, specialized mechanisms enforce lineage- and
      stage-specific recombination. 

PMID- 26301569
TI  - Induction of eryptosis by low concentrations of E. coli alpha-hemolysin.
AB  - Uropathogenic strains of Escherichia coli deliver the toxin alpha-hemolysin
      (HlyA) to optimize the host environment for the spread of infection. It was
      reported that at high concentrations, the toxin forms pores in eukaryotic
      membranes, leading to cell lysis, while lower concentrations have appeared to
      interfere with host-cell-signaling pathways causing cell death by apoptosis.
      Nevertheless, what is not clear is how often HlyA reaches levels that are high
      enough to lyse host target cells during the course of an infection. In the
      present investigation, we demonstrate that a low toxin concentration induces the
      suicidal death of erythrocytes (eryptosis), the major cell type present in blood.
      Eryptosis is triggered both by an increment in intracellular calcium and by
      ceramide. Since we have previously demonstrated that a low concentration of HlyA
      induces an increase in intraerythrocyte calcium, in the present experiments we
      have shown that this ion activates calpains, which hydrolyze skeleton proteins
      such as spectrin, ankyrin, protein 4.1 and the electrophoretic Band-3 species,
      thus resulting in morphologic changes in the erythrocytes. We furthermore
      observed that a low toxin concentration induced the activation of endogenous
      sphingomyelinases that in turn increased the amount of ceramide in erythrocyte
      membranes. Both spectrin proteolysis and ceramide formation may cause the
      exposure of phosphatidylserine on the membrane so as to trigger a macrophage
      engulfment of the erythrocyte. By this means eryptosis may be an advantageous
      mechanism for removing defective erythrocytes before hemolysis. 

PMID- 26301568
TI  - Wear transition of solid-solution-strengthened Ti-29Nb-13Ta-4.6Zr alloys by
      interstitial oxygen for biomedical applications.
AB  - In previous studies, it has been concluded that volume losses (V loss) of the Ti
      29Nb-13Ta-4.6Zr (TNTZ) discs and balls are larger than those of the respective Ti
      6Al-4V extra-low interstitial (Ti64) discs and balls, both in air and Ringer's
      solution. These results are related to severe subsurface deformation of TNTZ,
      which is caused by the lower resistance to plastic shearing of TNTZ than that of
      Ti64. Therefore, it is necessary to further increase the wear resistance of TNTZ
      to satisfy the requirements as a biomedical implant. From this viewpoint,
      interstitial oxygen was added to TNTZ to improve the plastic shear resistance via
      solid-solution strengthening. Thus, the wear behaviors of combinations comprised
      of a new titanium alloy, TNTZ with high oxygen content of 0.89 mass% (89O) and a
      conventional titanium alloy, Ti64 were investigated in air and Ringer's solution
      for biomedical implant applications. The worn surfaces, wear debris, and
      subsurface damage were analyzed using a scanning electron microscopy and an
      electron probe microanalysis. V loss of the 89O discs and balls are smaller than
      those of the respective TNTZ discs and balls in both air and Ringer's solution.
      It can be concluded that the solid-solution strengthening by oxygen effectively
      improves the wear resistance for TNTZ materials. However, the 89O disc/ball
      combination still exhibits higher V loss than the Ti64 disc/ball combination in
      both air and Ringer's solution. Moreover, V loss of the disc for the 89O
      disc/Ti64 ball combination significantly decreases in Ringer's solution compared
      to that in air. This decrease for the 89O disc/Ti64 ball combination in Ringer's
      solution can be explained by the transition in the wear mechanism from severe
      delamination wear to abrasive wear.

PMID- 26301571
TI  - External Electric Field Effects on Excited-State Intramolecular Proton Transfer
      in 4'-N,N-Dimethylamino-3-hydroxyflavone in Poly(methyl methacrylate) Films.
AB  - The external electric field effects on the steady-state electronic spectra and
      excited-state dynamics were investigated for 4'-N,N-(dimethylamino)-3
      hydroxyflavone (DMHF) in a poly(methyl methacrylate) (PMMA) film. In the steady
      state spectrum, dual emission was observed from the excited states of the normal
      (N*) and tautomer (T*) forms. Application of an external electric field of 1.0
      MV.cm(-1) enhanced the N* emission and reduced the T* emission, indicating that
      the external electric field suppressed the excited-state intramolecular proton
      transfer (ESIPT). The fluorescence decay profiles were measured for the N* and T*
      forms. The change in the emission intensity ratio N*/T* induced by the external
      electric field is dominated by ESIPT from the Franck-Condon excited state of the
      N* form and vibrational cooling in potential wells of the N* and T* forms
      occurring within tens of picoseconds. Three manifolds of fluorescent states were
      identified for both the N* and T* forms. The excited-state dynamics of DMHF in
      PMMA films has been found to be very different from that in solution due to
      intermolecular interactions in a rigid environment. 

PMID- 26301572
TI  - First Case of Systemic Coronavirus Infection in a Domestic Ferret (Mustela
      putorius furo) in Peru.
AB  - A domestic ferret from Lima, Peru, died after ten days of non-specific clinical
      signs. Based on pathology, immunohistochemistry and molecular analysis, ferret
      systemic coronavirus (FRSCV)-associated disease was diagnosed for the first time
      in South America. This report highlights the potential spread of pathogens by the
      international pet trade. 

PMID- 26301570
TI  - Tryptophan probes reveal residue-specific phospholipid interactions of
      apolipoprotein C-III.
AB  - Apolipoproteins are essential human proteins for lipid metabolism. Together with
      phospholipids, they constitute lipoproteins, nm to MUm sized particles
      responsible for transporting cholesterol and triglycerides throughout the body.
      To investigate specific protein-lipid interactions, we produced and characterized
      three single-Trp containing apolipoprotein C-III (ApoCIII) variants (W42
      (W54F/W65F), W54 (W42F/W65F), W65 (W42F/W54F)). Upon binding to phospholipid
      vesicles, wild-type ApoCIII adopts an alpha-helical conformation (50% helicity)
      as determined by circular dichroism spectroscopy with an approximate apparent
      partition constant of 3*10(4) M(-1). Steady-state and time-resolved fluorescence
      measurements reveal distinct residue-specific behaviors with W54 experiencing the
      most hydrophobic environment followed by W42 and W65. Interestingly, time
      resolved anisotropy measurements show a converse trend for relative Trp mobility
      with position 54 being the least immobile. To determine the relative insertion
      depths of W42, W54, and W65 in the bilayer, fluorescence quenching experiments
      were performed using three different brominated lipids. W65 had a clear
      preference for residing near the headgroup while W54 and W42 sample the range of
      depths ~8-11 A from the bilayer center. On average, W54 is slightly more embedded
      than W42. Based on Trp spectral differences between ApoCIII binding to
      phospholipid vesicles and sodium dodecyl sulfate micelles, we suggest that
      ApoCIII adopts an alternate helical conformation on the bilayer which could have
      functional implications.

PMID- 26301573
TI  - Fluorogenic Green-Inside Red-Outside (GIRO) Labeling Approach Reveals Adenylyl
      Cyclase-Dependent Control of BKalpha Surface Expression.
AB  - The regulation of surface levels of protein is critical for proper cell function
      and influences properties including cell adhesion, ion channel contributions to
      current flux, and the sensitivity of surface receptors to ligands. Here we
      demonstrate a two-color labeling system in live cells using a single fluorogen
      activating peptide (FAP) based fusion tag, which enables the rapid and
      simultaneous quantification of surface and internal proteins. In the nervous
      system, BK channels can regulate neural excitability and neurotransmitter
      release, and the surface trafficking of BK channels can be modulated by signaling
      cascades and assembly with accessory proteins. Using this labeling approach, we
      examine the dynamics of BK channel surface expression in HEK293 cells. Surface
      pools of the pore-forming BKalpha subunit were stable, exhibiting a plasma
      membrane half-life of >10 h. Long-term activation of adenylyl cyclase by
      forskolin reduced BKalpha surface levels by 30%, an effect that could not be
      attributed to increased bulk endocytosis of plasma membrane proteins. This
      labeling approach is compatible with microscopic imaging and flow cytometry,
      providing a solid platform for examining protein trafficking in living cells. 

PMID- 26301575
TI  - Nickel Ferrite Nanoparticles Anchored onto Silica Nanofibers for Designing
      Magnetic and Flexible Nanofibrous Membranes.
AB  - Many applications proposed for magnetic silica nanofibers require their assembly
      into a cellular membrane structure. The feature to keep structure stable upon
      large deformation is crucial for a macroscopic porous material which functions
      reliably. However, it remains a key issue to realize robust flexibility in two
      dimensional (2D) magnetic silica nanofibrous networks. Here, we report that the
      combination of electrospun silica nanofibers with zein dip-coating can lead to
      the formation of flexible, magnetic, and hierarchical porous silica nanofibrous
      membranes (SNM). The 290 nm diameter silica nanofibers act as templates for the
      uniform anchoring of nickel ferrite nanoparticles (size of 50 nm). Benefiting
      from the homogeneous and stable nanofiber-nanoparticle composite structure, the
      resulting magnetic SNM can maintain their structure integrity under repeated
      bending as high as 180 degrees  and can facilely recover. The unique hierarchical
      structure also provides this new class of silica membrane with integrated
      properties of ultralow density, high porosity, large surface area, good magnetic
      responsiveness, robust dye adsorption capacity, and effective emulsion separation
      performance. Significantly, the synthesis of such fascinating membranes may
      provide new insight for further application of silica in a self-supporting,
      structurally adaptive, and 2D membrane form. 

PMID- 26301574
TI  - Phylogeny of Acronychia (Rutaceae) and First Insights into Its Historical
      Biogeography and the Evolution of Fruit Characters.
AB  - BACKGROUND: The genus Acronychia (Citrus family, Rutaceae) contains 49 species of
      trees and shrubs that are found mainly in rain forest. The genus has a large
      distributional range from mainland southern Asia to Australia and New Caledonia,
      but most species are endemic to either New Guinea or Australia. This study aimed
      to provide the first detailed molecular phylogeny of Acronychia and use it to
      test the taxonomic value of fruit morphological characters, and infer the
      historical biogeography of the genus. METHODOLOGY: Phylogenetic analyses
      (Bayesian Inference, Maximum Likelihood) were undertaken on nucleotide sequence
      data from two plastid (psbA-trnH, trnL-trnF) and three nuclear markers (ETS, ITS,
      NIAi3) from 29 Acronychia species (59% of the genus) and representatives of
      related genera. RESULTS AND CONCLUSIONS: The results indicate that the South-East
      Asian genus Maclurodendron is nested phylogenetically within Acronychia and must
      be synonymized to render Acronychia monophyletic. Fruit morphological characters
      have been used previously to infer relationships within Acronychia and our
      analyses show that these characters are informative for some subclades but are
      homoplasious for the group as a whole. Apocarpous fruits are the ancestral state
      in Acronychia and subapocarpous and fully syncarpous fruits are derived. The
      unisexual flowers of Maclurodendron are derived from bisexual flowers, which are
      found in all species of Acronychia as well as its relatives. Acronychia probably
      first evolved on Australia with range expansion to New Guinea via stepping-stone
      dispersal or direct land connections within the Sahul Shelf, followed by two
      independent dispersals to areas west of New Guinea. Most species of Acronychia
      occur in either Australia or New Guinea, but no species occurs in both regions.
      This is surprising given the close proximity of the landmasses, but might be
      explained by ecological factors.

PMID- 26301577
TI  - Plasma YKL-40 during pregnancy and gestational diabetes mellitus.
AB  - Gestational diabetes mellitus (GDM) is characterised by hyperglycaemia during
      pregnancy. The clinical circumstances involved in the development of GDM leaves
      the patient at a high risk of the subsequent development of type 2 diabetes.
      Plasma levels of the inflammation marker YKL-40 are elevated in type 2 diabetes
      and correlate with fasting plasma glucose levels and insulin resistance in
      patients with type 2 diabetes. With the present study we aimed to determine if
      pregnancy (and associated insulin resistance) with or without GDM affects plasma
      YKL-40 levels. Plasma from women diagnosed with GDM and healthy normal glucose
      tolerant pregnant women (non-GDM) was obtained at the third trimester of
      pregnancy and again 3-4 months following delivery, and levels of YKL-40 and
      interleukin 6 (IL-6; known to regulate YKL-40) were measured. Plasma YKL-40
      levels were similarly low during pregnancy in both groups and increased
      significantly after delivery, but remained lower in the GDM group compared with
      the non-GDM group postpartum. In contrast, plasma IL-6 levels were not affected
      by pregnancy or diagnosis of GDM, Nevertheless, YKL-40 levels were associated
      with IL-6 levels in the non-GDM group (but not in the GDM group). Pregnancy seems
      to be associated with a temporary reduction in circulating YKL-40, which
      increases after delivery, but to a much lesser extent in women with GDM than in
      non-GDM women. 

PMID- 26301578
TI  - Synthesis of 1D Silica Nanostructures with Controllable Sizes Based on Short
      Anionic Peptide Self-Assembly.
AB  - Artificial synthesis of silica under benign conditions is usually achieved by
      using cationic organic matrices as templates while the anionic analogues have not
      received enough consideration, albeit they are also functioning in biosilica
      formation. In this work, we report the design and self-assembly of an anionic
      peptide amphiphile (I3E) and the use of its self-assemblies as templates to
      synthesize 1D silica nanostructures with tunable sizes. We show that short I3E
      readily formed long nanofibrils in aqueous solution via a hierarchical self
      assembly process. By using APTES and TEOS as silica precursors, we found that the
      I3E nanofibrils templated the production of silica nanotubes with a wide size
      distribution, in which the silica size regulation was achieved by tuning the
      interactions among the peptide template and silicon species. These results
      clearly illustrate a facile method for generating silica nanomaterials based on
      anionic matrices. 

PMID- 26301576
TI  - Impact of Surface Polyethylene Glycol (PEG) Density on Biodegradable Nanoparticle
      Transport in Mucus ex Vivo and Distribution in Vivo.
AB  - Achieving sustained drug delivery to mucosal surfaces is a major challenge due to
      the presence of the protective mucus layer that serves to trap and rapidly remove
      foreign particulates. Nanoparticles engineered to rapidly penetrate mucosal
      barriers (mucus-penetrating particles, "MPP") have shown promise for improving
      drug distribution, retention and efficacy at mucosal surfaces. MPP are densely
      coated with polyethylene glycol (PEG), which shields the nanoparticle core from
      adhesive interactions with mucus. However, the PEG density required to impart the
      "stealth" properties to nanoparticles in mucus, and thus, uniform distribution in
      vivo, is still unknown. We prepared biodegradable poly(lactic-co-glycolic acid)
      (PLGA) nanoparticles with a range of PEG surface densities by blending various
      ratios of a diblock copolymer of PLGA and 5 kDa poly(ethylene glycol) (PLGA
      PEG5k) with PLGA. We then evaluated the impact of PEG surface density, measured
      using an (1)H NMR method, on mucin binding in vitro, nanoparticle transport in
      freshly obtained human cervicovaginal mucus (CVM) ex vivo, and nanoparticle
      distribution in the mouse cervicovaginal tract in vivo. We found that at least 5%
      PEG was required to effectively shield the nanoparticle core from interacting
      with mucus components in vitro and ex vivo, thus leading to enhanced nanoparticle
      distribution throughout the mouse vagina in vivo. We then demonstrated that
      biodegradable MPP could be formulated from blends of PLGA and PLGA-PEG polymers
      of various molecular weights, and that these MPP provide tunable drug loading and
      drug release rates and durations. Overall, we describe a methodology for
      rationally designing biodegradable, drug-loaded MPP for more uniform delivery to
      the vagina. 

PMID- 26301580
TI  - Letter from the Editor.

PMID- 26301579
TI  - Association between the Lipid Levels and Single Nucleotide Polymorphisms of
      ABCA1, APOE and HMGCR Genes in Subjects with Spontaneous Preterm Delivery.
AB  - Spontaneous preterm delivery (SPTD) with gestational age between 28 and 37
      complete weeks was reported to have a genetic predisposition in lipids
      metabolism. This study aimed to investigate the association between the lipid
      levels and gene polymorphisms of ABCA1 (rs2422493), APOE (rs7412) and HMGCR
      (rs12916) in Chinese pregnant women with SPTD. A case-control study was conducted
      at the baseline randomization in 200 SPTD and 178 healthy full term delivery
      (FTD) women. Maternal blood lipids were detected close to delivery of fetus in
      SPTD group and in FTD group with gestational age-matched. Cord blood lipids were
      detected after delivery in two groups. Three genotypes both in maternal and cord
      blood were determined by real time PCR. The results showed that the levels of
      total cholesterol (TCHO), triglyceride (TG), high density lipoprotein (HDL), and
      low-density lipoprotein cholesterol (LDL) in the maternal blood in the SPTD group
      were significantly lower than those in the FTD group, while the levels of TCHO,
      HDL, and LDL in the cord blood in the SPTD group were significantly higher than
      those in the FTD group. In the SPTD subjects, the levels of TG and LDL in the
      maternal blood were associated with different genotypes of HMGCR gene rs12916
      loci. These results indicate that abnormal lipid metabolism may exist in SPTD
      women and the premature fetus and the HMGCR gene may be a susceptible gene for
      SPTD. 

PMID- 26301582
TI  - A Prospective Cohort Study To Evaluate the Feasibility of Intraoperative
      Antimicrobial Prophylaxis in Open Gastrectomy for Gastric Cancer.
AB  - BACKGROUND: The optimal duration of antimicrobial prophylaxis (AMP) in patients
      undergoing gastric cancer surgery remains debatable. The aim of this prospective
      cohort study was to evaluate the feasibility of intraoperative AMP in comparison
      with conventional AMP in patients undergoing elective open gastrectomy. METHODS:
      The duration of AMP was shortened in two six-monthly stages in patients
      undergoing open gastrectomy for gastric cancer, and the incidences of surgical
      site infections (SSIs) and remote infections (RIs) were surveyed. In the first
      stage (September 2004 to February 2005), the patients received four intravenous
      injections of cefazolin 1 g at 12-h intervals starting from 30 min before surgery
      (conventional AMP). In the second stage (March 2005 to August 2005), the patients
      received the same agent at three-h intervals starting 30 min before surgery and
      continuing until the end of the operation (intraoperative AMP). RESULTS: A total
      of 423 patients were enrolled, including 202 patients operated on in the first
      stage of cancer and 221 patients operated on in the second stage. The patient
      characteristics in the two stages were well balanced. There was no significant
      difference in the incidence of SSIs (10.4% vs. 8.1%; odds ratio [OR], 0.764; 95%
      confidence interval [CI] 0.395-1.480; p = 0.528) or RIs (7.9% vs. 5.9%; OR 0.727;
      95% CI 0.340-1.551; p = 0.525) between the two stages. There were no serious
      adverse events related to the AMP. The treatment effects on the SSIs were similar
      in all subgroups of patients analyzed. There was no appreciable difference in the
      trend in the causative pathogens of the SSIs and RIs between the two stages.
      CONCLUSIONS: Intraoperative and conventional AMP were associated with similar
      incidences of SSIs and RIs. Intraoperative AMP appears to be feasible and
      sufficient in patients undergoing open gastrectomy for gastric cancer.

PMID- 26301583
TI  - T-loop force system with and without vertical step using finite element analysis.
AB  - OBJECTIVE: To investigate the effect of vertical steps on a T-loop force system
      at three interbracket distances (IBDs) and their association with V-bends.
      MATERIALS AND METHODS: Loop response during simulated loop pulling was determined
      for 18 T-loop configurations (6-, 9-, and 12-mm IBD with a 2.5-mm canine bracket
      (CB) end and 0- (plain), 0.5-, or 1-mm vertical step). Loop length-by-height was
      8 * 8 or 10 * 10 mm. Horizontal load/deflection, vertical force (Fy), and moment
      to-force (M/F) ratios at loop ends were determined for 100-g and 200-g activation
      by finite element analysis. RESULTS: Plain, 12-mm IBD T-loops showed similar
      force and moment responses as off-centered V-bends (greater moment close to V
      bend) without change in moment direction at the premolar bracket (PB) end; plain,
      6-mm IBD T-loop responses were similar to those of centered V-bends (equal,
      opposing moments at each end). Adding vertical steps to the T-loops raised the
      M/F ratio at the PB ends enough to produce root movement, while lowering the M/F
      ratios at the CB ends. Increasing the step bends for shorter IBDs increased Fys
      and caused rapid changes in M/F ratios. Unlike plain T-loops, increasing
      activation in stepped T-loops caused substantial variations in M/F ratios and in
      amount and direction of Fys. CONCLUSIONS: Step bends can dramatically change the
      force system. Stepped T-loops display combined effects of V-bends and step bends.

PMID- 26301584
TI  - [Not Available].

PMID- 26301586
TI  - [Not Available].

PMID- 26301585
TI  - [Not Available].

PMID- 26301587
TI  - [Not Available].

PMID- 26301588
TI  - Suicide risk after nonfatal self-harm: a national cohort study, 2000-2008.
AB  - OBJECTIVE: To study the short-term risk of suicide after nonfatal deliberate self
      harm and its association with coexisting mental disorders and with the method of
      self-harm used. METHOD: We used linked Swedish national registers to design a
      cohort study with 34,219 individuals (59% females) who were admitted to hospital
      in 2000-2005 after deliberate self-harm (ICD-10-defined). They were followed for
      3-9 years. The studied outcome was completed suicide; Cox regression models
      yielded hazard ratios (HRs) for suicide risk. Temporal patterns were plotted with
      Kaplan-Meier survival curves, calculated separately for each mental disorder and
      for the method used at the previous self-harm event. RESULTS: 1,182 subjects
      committed suicide during follow-up (670 males and 512 females). Coexisting
      bipolar disorder (in males, adjusted HR = 6.3; 95% confidence interval [CI], 3.8
      10.3; in females, adjusted HR = 5.8; 95% CI, 3.4-9.7) and nonorganic psychotic
      disorder (in males, adjusted HR = 5.1; 95% CI, 3.5-7.4; in females, adjusted HR =
      4.6; 95% CI, 2.8-7.7) implied the highest risk of suicide after previous self
      harm. Hanging as index self-harm method was a strong predictor of later suicide
      in both males (adjusted HR = 5.3; 95% CI, 4.0-7.0) and females (adjusted HR =
      4.5; 95% CI, 2.5-8.1). Of those with bipolar disorder who used a method other
      than poisoning at the index event, 20.4% had already committed suicide after 3-9
      years. CONCLUSION: Individuals with severe mental disorders (affective and
      psychotic disorders) have a poor prognosis in the first years after hospital
      admission due to self-harm. The risk of subsequent suicide is higher after
      attempts by hanging and other self-injury methods (vs self-poisoning). Aftercare
      for those with a self-harm episode should focus on treatment of the mental
      disorder present at the time of the episode.

PMID- 26301589
TI  - Heterogeneous Disease Trajectories Explain Variable Radiographic, Function and
      Quality of Life Outcomes in the Canadian Early Arthritis Cohort (CATCH).
AB  - Our objective was to identify distinct trajectories of disease activity state
      (DAS) and assess variation in radiographic progression, function and quality of
      life over the first two years of early rheumatoid arthritis (ERA). The CATCH
      (Canadian early ArThritis CoHort) is a prospective study recruiting ERA patients
      from academic and community rheumatology clinics in Canada. Sequential DAS28
      scores were used to identify five mutually exclusive groups in the cohort (n =
      1,586) using growth-based trajectory modeling. Distinguishing baseline
      sociodemographic and disease variables, treatment required, and differences in
      radiographic progression and quality of life measures over two years were
      assessed. The trajectory groups are characterized as: Group 1 (20%) initial high
      DAS improving rapidly to remission (REM); Group 2 (21%) initial moderate DAS
      improving rapidly to REM; Group 3 (30%) initial moderate DAS improving gradually
      to low DAS; Group 4 (19%) initial high DAS improving continuously to low DAS; and
      Group 5 (10%) initial high DAS improving gradually only to moderate DAS. Groups
      differed significantly in age, sex, race, education, employment, income and
      presence of comorbidities. Group 5 had persistent steroid requirements and the
      highest biologic therapy use. Group 2 had lower odds (OR 0.22, 95%CI 0.09 to
      0.58) and Group 4 higher odds (OR 1.94, 95%CI 0.90 to 4.20) of radiographic
      progression compared to Group 1. Group 1 had the best improvement in physical
      function (Health Assessment Questionnaire 1.08 (SD 0.68) units), Physical
      Component Score (16.4 (SD 10.2) units), Mental Component Score (9.7 (SD 12.5)
      units) and fatigue (4.1 (SD 3.3) units). In conclusion, distinct disease activity
      state trajectories explain variable outcomes in ERA. Early prediction of disease
      course to tailor therapy and addressing social determinants of health could
      optimize outcomes. 

PMID- 26301591
TI  - Trauma and Poor Mental Health in Relation to Economic Status: The Case of
      Cambodia 35 Years Later.
AB  - BACKGROUND: Cambodia is one of the poorest countries in south-east Asia and is
      still emerging from the events of the Khmer Rouge reign. It has been suggested
      that the atrocities experienced by the Cambodian population can explain why
      Cambodia continues to lag behind its neighbours in economic outcomes. The purpose
      of this study is to investigate whether there is an association between exposure
      to past trauma and/or current poor mental health and current economic status in
      Cambodia. METHOD: A newly conducted survey performed in two regions (north-west
      and south-east Cambodia) collected information on trauma exposure, psychiatric
      symptoms, self-rated health outcomes and socio-economic information for 3200
      persons aged 18-60. Economic outcomes were measured as household debt and poverty
      status and whether the respondent was economically inactive. All models were
      analysed using logistic regression. RESULTS: No association was found between
      high exposure to conflict-related or civilian trauma and any economic outcomes
      save for a negative association between civilian trauma and poverty in the south
      east. Current post-traumatic stress was related solely to poverty status. All
      other measures of current mental health status, however, were found to be
      strongly negatively associated with all measures of economic status. Thus, mental
      health interventions could potentially be utilised in poverty reduction
      strategies, but greater efficacy is likely to be achieved by targeting current
      mental health status rather than previous trauma exposure.

PMID- 26301590
TI  - Effects of Tobacco Smoking on the Degeneration of the Intervertebral Disc: A
      Finite Element Study.
AB  - Tobacco smoking is associated with numerous pathological conditions. Compelling
      experimental evidence associates smoking to the degeneration of the
      intervertebral disc (IVD). In particular, it has been shown that nicotine down
      regulates both the proliferation rate and glycosaminoglycan (GAG) biosynthesis of
      disc cells. Moreover, tobacco smoking causes the constriction of the vascular
      network surrounding the IVD, thus reducing the exchange of nutrients and anabolic
      agents from the blood vessels to the disc. It has been hypothesized that both
      nicotine presence in the IVD and the reduced solute exchange are responsible for
      the degeneration of the disc due to tobacco smoking, but their effects on tissue
      homeostasis have never been quantified. In this study, a previously presented
      computational model describing the homeostasis of the IVD was deployed to
      investigate the effects of impaired solute supply and nicotine-mediated down
      regulation of cell proliferation and biosynthetic activity on the health of the
      disc. We found that the nicotine-mediated down-regulation of cell anabolism
      mostly affected the GAG concentration at the cartilage endplate, reducing it up
      to 65% of the value attained in normal physiological conditions. In contrast, the
      reduction of solutes exchange between blood vessels and disc tissue mostly
      affected the nucleus pulposus, whose cell density and GAG levels were reduced up
      to 50% of their normal physiological levels. The effectiveness of quitting
      smoking on the regeneration of a degenerated IVD was also investigated, and
      showed to have limited benefit on the health of the disc. A cell-based therapy in
      conjunction with smoke cessation provided significant improvements in disc
      health, suggesting that, besides quitting smoking, additional treatments should
      be implemented in the attempt to recover the health of an IVD degenerated by
      tobacco smoking. 

PMID- 26301592
TI  - Genome Sequence Analysis of the Naphthenic Acid Degrading and Metal Resistant
      Bacterium Cupriavidus gilardii CR3.
AB  - Cupriavidus sp. are generally heavy metal tolerant bacteria with the ability to
      degrade a variety of aromatic hydrocarbon compounds, although the degradation
      pathways and substrate versatilities remain largely unknown. Here we studied the
      bacterium Cupriavidus gilardii strain CR3, which was isolated from a natural
      asphalt deposit, and which was shown to utilize naphthenic acids as a sole carbon
      source. Genome sequencing of C. gilardii CR3 was carried out to elucidate
      possible mechanisms for the naphthenic acid biodegradation. The genome of C.
      gilardii CR3 was composed of two circular chromosomes chr1 and chr2 of
      respectively 3,539,530 bp and 2,039,213 bp in size. The genome for strain CR3
      encoded 4,502 putative protein-coding genes, 59 tRNA genes, and many other non
      coding genes. Many genes were associated with xenobiotic biodegradation and metal
      resistance functions. Pathway prediction for degradation of cyclohexanecarboxylic
      acid, a representative naphthenic acid, suggested that naphthenic acid undergoes
      initial ring-cleavage, after which the ring fission products can be degraded via
      several plausible degradation pathways including a mechanism similar to that used
      for fatty acid oxidation. The final metabolic products of these pathways are
      unstable or volatile compounds that were not toxic to CR3. Strain CR3 was also
      shown to have tolerance to at least 10 heavy metals, which was mainly achieved by
      self-detoxification through ion efflux, metal-complexation and metal-reduction,
      and a powerful DNA self-repair mechanism. Our genomic analysis suggests that CR3
      is well adapted to survive the harsh environment in natural asphalts containing
      naphthenic acids and high concentrations of heavy metals. 

PMID- 26301594
TI  - Effect of Bromine Substitution on Human Dermal Absorption of Polybrominated
      Diphenyl Ethers.
AB  - Human dermal absorption of eight mono- to deca-brominated diphenyl ethers (PBDEs)
      was investigated for the first time using EPISKIN human skin equivalent tissue.
      Using a standard in vitro protocol, EPISKIN tissues mounted in specially designed
      diffusion cells were exposed to the target PBDEs for 24 h. Estimated steady-state
      flux (Jss) and permeation coefficients (Papp) across the skin increased with
      decreasing bromine substitution from BDE-153 (Papp = 4.0 * 10(-4) cm/h) to BDE-1
      (Papp = 1.1 * 10(-2) cm/h). This was accompanied by an increase in the time
      required to traverse the skin tissue into the receptor fluid (lag time) from 0.25
      h for BDE-1 to 1.26 h for BDE-153. Papp values for the studied PBDEs were
      correlated significantly (P < 0.05) with physicochemical parameters like water
      solubility and log KOW. While less brominated congeners achieved faster dermal
      penetration, higher PBDEs displayed greater accumulation within the skin tissue.
      The PBDEs thus accumulated represent a contaminant depot from which they may be
      slowly released to the systemic circulation over a prolonged period. Maximal
      percutaneous penetration was observed for BDE-1 (~ 30% of the applied 500
      ng/cm(2) dose). Interestingly, BDE-183 and BDE-209 showed very low dermal
      absorption, exemplified by a failure to reach the steady state within the 24 h
      exposure period that was studied.

PMID- 26301593
TI  - Source and Purity of Dengue-Viral Preparations Impact Requirement for Enhancing
      Antibody to Induce Elevated IL-1beta Secretion: A Primary Human Monocyte Model.
AB  - Dengue virus is a major global health threat and can lead to life-threatening
      hemorrhagic complications due to immune activation and cytokine production. Cross
      reactive antibodies to an earlier dengue virus infection are a recognized risk
      factor for severe disease. These antibodies bind heterologous dengue serotypes
      and enhance infection into Fc-receptor-bearing cells, a process known as antibody
      dependent enhancement of infection. One crucial cytokine seen elevated in severe
      dengue patients is IL-1beta, a potent inflammatory cytokine matured by the
      inflammasome. We used a highly-physiologic system by studying antibody-dependent
      enhancement of IL-1beta in primary human monocytes with anti-dengue human
      monoclonal antibodies isolated from patients. Antibody-enhancement increased
      viral replication in primary human monocytes inoculated with supernatant
      harvested from Vero cells infected with dengue virus serotype 2 (DENV-2) 16681.
      Surprisingly, IL-1beta secretion induced by infectious supernatant harvested from
      two independent Vero cell lines was not enhanced by antibody. Secretion of
      multiple other inflammatory cytokines was also independent of antibody signaling.
      However, IL-1beta secretion did require NLRP3 and caspase-1 activity.
      Immunodepletion of dengue virions from the infectious supernatant confirmed that
      virus was not the main IL-1beta-inducing agent, suggesting that a supernatant
      component(s) not associated with the virion induced IL-1beta production. We
      excluded RNA, DNA, contaminating LPS, viral NS1 protein, complement, and
      cytokines. In contrast, purified Vero-derived DENV-2 16681 exhibited antibody
      enhancement of both infection and IL-1beta induction. Furthermore, C6/36 mosquito
      cells did not produce such an inflammatory component, as crude supernatant
      harvested from insect cells infected with DENV-2 16681 induced antibody-dependent
      IL-1beta secretion. This study indicates that Vero cells infected with DENV-2
      16681 may produce inflammatory components during dengue virus propagation that
      mask the virus-specific immune response. Thus, the choice of host cell and viral
      purity should be carefully considered, while insect-derived virus represents a
      system that elicits antibody-dependent cytokine responses to dengue virus with
      fewer confounding issues. 

PMID- 26301595
TI  - Exercise mitigates cumulative associations between stress and BMI in girls age 10
      to 19.
AB  - OBJECTIVE: Long-term psychological stress is associated with BMI increases in
      children as they transition to adulthood, whereas long-term maintenance of
      physical activity can slow excess weight gain. We hypothesized that in addition
      to these main effects, long-term physical activity mitigates the relationship
      between long-term stress and BMI increase. METHOD: The NHLBI Growth and Health
      Study enrolled 2,379 10-year-old Black and White girls, following them annually
      for 10 measurement points. Growth curve modeling captured the dynamics of BMI,
      measured yearly, and stress and physical activity, measured at varying years.
      RESULTS: At average levels of activity and stress, with all covariates remaining
      fixed, average BMI at baseline was 19.74 (SE = 0.38) and increased 0.64 BMI (SE =
      0.01, p < .001) units every year. However, this increase in BMI significantly
      varied as a function of cumulative stress and physical activity. Slower BMI gain
      occurred in those girls who were less stressed and more active (0.62 BMI
      units/year, SE = .02, p < .001), whereas the most rapid and largest growth
      occurred in girls who were more stressed and less active (0.92 BMI units/year, SE
      = .02, p < .001). Racial identification did not alter these effects. CONCLUSIONS:
      As hypothesized, in girls who maintained long-term activity, BMI growth was
      mitigated, even when reporting high long-term stress, compared with less
      physically active girls. This study adds to a converging literature in which
      physical activity, a modifiable prevention target, functions to potentially limit
      the damaging health effects of long-term psychological stress.

PMID- 26301596
TI  - Female choice for male cuticular hydrocarbon profile in decorated crickets is not
      based on similarity to their own profile.
AB  - Indirect genetic benefits derived from female mate choice comprise additive (good
      genes) and nonadditive genetic benefits (genetic compatibility). Although good
      genes can be revealed by condition-dependent display traits, the mechanism by
      which compatibility alleles are detected is unclear because evaluation of the
      genetic similarity of a prospective mate requires the female to assess the
      genotype of the male and compare it to her own. Cuticular hydrocarbons (CHCs),
      lipids coating the exoskeleton of most insects, influence female mate choice in a
      number of species and offer a way for females to assess genetic similarity of
      prospective mates. Here, we determine whether female mate choice in decorated
      crickets is based on male CHCs and whether it is influenced by females' own CHC
      profiles. We used multivariate selection analysis to estimate the strength and
      form of selection acting on male CHCs through female mate choice, and employed
      different measures of multivariate dissimilarity to determine whether a female's
      preference for male CHCs is based on similarity to her own CHC profile. Female
      mating preferences were significantly influenced by CHC profiles of males. Male
      CHC attractiveness was not, however, contingent on the CHC profile of the
      choosing female, as certain male CHC phenotypes were equally attractive to most
      females, evidenced by significant linear and stabilizing selection gradients.
      These results suggest that additive genetic benefits, rather than nonadditive
      genetic benefits, accrue to female mate choice, in support of earlier work
      showing that CHC expression of males, but not females, is condition dependent.

PMID- 26301597
TI  - Competitive exclusion principle in ecology and absolute asymmetric synthesis in
      chemistry.
AB  - The key concepts underlying the Frank model (1953) for spontaneous asymmetric
      synthesis in chemistry are traced back to the pioneering works of Volterra (1926)
      and Lotka (1932) on biological species competition. The Lotka-Volterra (L-V) two
      species exclusive competition model reduces to the Frank model for the special
      case of distinguishable but degenerate species (i.e., the enantiomers). The
      important ecological principle of competitive exclusion, originally derived from
      the L-V two-competitors model, is a consequence of sufficiently antagonistic
      interactions between the species competing for limited common resources, or
      mutual inhibition, as the term is known in the chemical literature on absolute
      asymmetric synthesis. The L-V and Frank models are described by the same general
      differential equations, nevertheless a crucial thermodynamic distinction between
      these models is necessary to correlate ecological selection and chemical
      selectivity arising from 1) the absence of reversibility in biological
      transformations, in marked contrast to chemical reactions, and 2) the constraints
      in chemical scenarios on the reaction rate constants required to fulfill the
      principle of micro-reversibility.

PMID- 26301598
TI  - Genetic analysis reveals multiple parentage in captive reared eastern hellbender
      salamanders (Cryptobranchus alleganiensis).
AB  - Information on the parentage of captive reared clutches is vital for conservation
      head-starting programs. Molecular methods, such as genotyping individuals with
      hyper-variable markers, can elucidate the genealogical contribution of captive
      reared, reintroduced individuals to native populations. In this study, we used 12
      polymorphic microsatellite loci to infer parentage of a clutch of 18 eastern
      hellbenders collected from a single nest from Buffalo Creek, West Virginia,
      subsequently reared in captivity, and used for translocations in Indiana.
      Collectively, these markers successfully detected the presence of multiple
      parentage for this species of conservation concern presently used in captive
      management programs in zoos across many states. This study highlights the need
      for genetic analysis of captive reared clutches used in translocations to
      minimize the loss of genetic diversity and potential for genetic swamping at
      release sites.

PMID- 26301599
TI  - Association between sap flow-derived and eddy covariance-derived measurements of
      forest canopy CO2 uptake.
AB  - The carbon sink intensity of the biosphere depends on the balance between gross
      primary productivity (GPP) of forest canopies and ecosystem respiration. GPP,
      however, cannot be directly measured and estimates are not well constrained. A
      new approach relying on canopy transpiration flux measured as sap flow, and water
      use efficiency inferred from carbon isotope analysis (GPPSF ) has been proposed,
      but not tested against eddy covariance-based estimates (GPPEC ). Here we take
      advantage of parallel measurements using the two approaches at a semi-arid pine
      forest site to compare the GPPSF and GPPEC estimates on diurnal to annual
      timescales. GPPSF captured the seasonal dynamics of GPPEC (GPPSF  = 0.99 * GPPEC
      , r(2)  = 0.78, RMSE = 0.82, n = 457 d) with good agreement at the annual
      timescale (653 vs 670 g C m(-2)  yr(-1) ). Both methods showed that GPP ranged
      between 1 and 8 g C m(-2)  d(-1) , and the GPPSF /GPPEC ratio was between 0.5 and
      2.0 during 82% of the days. Carbon uptake dynamics at the individual tree scale
      conformed with leaf scale rates of net assimilation. GPPSF can produce robust
      estimations of tree- and canopy-scale rates of CO2 uptake, providing constraints
      and greatly extending current GPPEC estimations. 

PMID- 26301600
TI  - Architecture of the Complex Formed by Large and Small Terminase Subunits from
      Bacteriophage P22.
AB  - Packaging of viral genomes inside empty procapsids is driven by a powerful ATP
      hydrolyzing motor, formed in many double-stranded DNA viruses by a complex of a
      small terminase (S-terminase) subunit and a large terminase (L-terminase)
      subunit, transiently docked at the portal vertex during genome packaging. Despite
      recent progress in elucidating the structure of individual terminase subunits and
      their domains, little is known about the architecture of an assembled terminase
      complex. Here, we describe a bacterial co-expression system that yields milligram
      quantities of the S-terminase:L-terminase complex of the Salmonella phage P22. In
      vivo assembled terminase complex was affinity-purified and stabilized by addition
      of non-hydrolyzable ATP, which binds specifically to the ATPase domain of L
      terminase. Mapping studies revealed that the N-terminus of L-terminase ATPase
      domain (residues 1-58) contains a minimal S-terminase binding domain sufficient
      for stoichiometric association with residues 140-162 of S-terminase, the L
      terminase binding domain. Hydrodynamic analysis by analytical ultracentrifugation
      sedimentation velocity and native mass spectrometry revealed that the purified
      terminase complex consists predominantly of one copy of the nonameric S-terminase
      bound to two equivalents of L-terminase (1S-terminase:2L-terminase). Direct
      visualization of this molecular assembly in negative-stained micrographs yielded
      a three-dimensional asymmetric reconstruction that resembles a "nutcracker" with
      two L-terminase protomers projecting from the C-termini of an S-terminase ring.
      This is the first direct visualization of a purified viral terminase complex
      analyzed in the absence of DNA and procapsid. 

PMID- 26301601
TI  - When the Scaffold Cannot Be Ignored: The Role of the Hydrophobic Core in Ligand
      Binding and Specificity.
AB  - The traditional view of protein-ligand binding treats a protein as comprising
      distinct binding epitopes on the surface of a degenerate structural scaffold,
      largely ignoring the impact of a protein's energy landscape. To determine the
      robustness of this simplification, we compared two small helix-turn-helix
      transcription factors with different energy landscapes. lambda-Repressor is
      stable and well folded, while MarA appears to be marginally stable with multiple
      native conformations (molten). While lambda-repressor is known to tolerate any
      hydrophobic mutation in the core, we find MarA drastically less tolerant to core
      mutation. Moreover, core mutations in MarA (distant from the DNA-binding
      interface) change the relative affinities of its binding partners, altering
      ligand specificity. These results can be explained by taking into account the
      effects of mutations on the entire energy landscape and not just the native
      state. Thus, for proteins with multiple conformations that are close in energy,
      such as many intrinsically disordered proteins, residues distant from the active
      site can alter both binding affinity and specificity. 

PMID- 26301602
TI  - Performance benchmarking of four cell-free protein expression systems.
AB  - Over the last half century, a range of cell-free protein expression systems based
      on pro- and eukaryotic organisms have been developed and have found a range of
      applications, from structural biology to directed protein evolution. While it is
      generally accepted that significant differences in performance among systems
      exist, there is a paucity of systematic experimental studies supporting this
      notion. Here, we took advantage of the species-independent translation initiation
      sequence to express and characterize 87 N-terminally GFP-tagged human cytosolic
      proteins of different sizes in E. coli, wheat germ (WGE), HeLa, and Leishmania
      based (LTE) cell-free systems. Using a combination of single-molecule
      fluorescence spectroscopy, SDS-PAGE, and Western blot analysis, we assessed the
      expression yields, the fraction of full-length translation product, and
      aggregation propensity for each of these systems. Our results demonstrate that
      the E. coli system has the highest expression yields. However, we observe that
      high expression levels are accompanied by production of truncated species
      particularly pronounced in the case of proteins larger than 70 kDa. Furthermore,
      proteins produced in the E. coli system display high aggregation propensity, with
      only 10% of tested proteins being produced in predominantly monodispersed form.
      The WGE system was the most productive among eukaryotic systems tested. Finally,
      HeLa and LTE show comparable protein yields that are considerably lower than the
      ones achieved in the E. coli and WGE systems. The protein products produced in
      the HeLa system display slightly higher integrity, whereas the LTE-produced
      proteins have the lowest aggregation propensity among the systems analyzed. The
      high quality of HeLa- and LTE-produced proteins enable their analysis without
      purification and make them suitable for analysis of multi-domain eukaryotic
      proteins.

PMID- 26301604
TI  - Short-course versus prolonged-course antibiotic therapy for hospital-acquired
      pneumonia in critically ill adults.
AB  - BACKGROUND: Pneumonia is the most common hospital-acquired infection affecting
      patients in the intensive care unit (ICU). However, current national guidelines
      for the treatment of hospital-acquired pneumonia (HAP) are several years old and
      the diagnosis of pneumonia in mechanically ventilated patients (VAP) has been
      subject to considerable recent attention. The optimal duration of antibiotic
      therapy for HAP in the critically ill is uncertain. OBJECTIVES: To assess the
      effectiveness of short versus prolonged-course antibiotics for HAP in critically
      ill adults, including patients with VAP. SEARCH METHODS: We searched CENTRAL
      (2015, Issue 5), MEDLINE (1946 to June 2015), MEDLINE in-process and other non
      indexed citations (5 June 2015), EMBASE (2010 to June 2015), LILACS (1982 to June
      2015) and Web of Science (1955 to June 2015). SELECTION CRITERIA: We considered
      all randomised controlled trials (RCTs) comparing a fixed 'short' duration of
      antibiotic therapy with a 'prolonged' course for HAP (including patients with
      VAP) in critically ill adults. DATA COLLECTION AND ANALYSIS: Two review authors
      conducted data extraction and assessment of risk of bias. We contacted trial
      authors for additional information. MAIN RESULTS: We identified six relevant
      studies involving 1088 participants. This included two new studies published
      after the date of our previous review (2011). There was substantial variation in
      participants, in the diagnostic criteria used to define an episode of pneumonia,
      in the interventions and in the reported outcomes. We found no evidence relating
      to patients with a high probability of HAP who were not mechanically ventilated.
      For patients with VAP, overall a short seven- or eight-day course of antibiotics
      compared with a prolonged 10- to 15-day course increased 28-day antibiotic-free
      days (two studies; N = 431; mean difference (MD) 4.02 days; 95% confidence
      interval (CI) 2.26 to 5.78) and reduced recurrence of VAP due to multi-resistant
      organisms (one study; N = 110; odds ratio (OR) 0.44; 95% CI 0.21 to 0.95),
      without adversely affecting mortality and other recurrence outcomes. However, for
      cases of VAP specifically due to non-fermenting Gram-negative bacilli (NF-GNB),
      recurrence was greater after short-course therapy (two studies, N = 176; OR 2.18;
      95% CI 1.14 to 4.16), though mortality outcomes were not significantly different.
      One study found that a three-day course of antibiotic therapy for patients with
      suspected HAP but a low Clinical Pulmonary Infection Score (CPIS) was associated
      with a significantly lower risk of superinfection or emergence of antimicrobial
      resistance, compared with standard (prolonged) course therapy. AUTHORS'
      CONCLUSIONS: On the basis of a small number of studies and appreciating the lack
      of uniform definition of pneumonia, we conclude that for patients with VAP not
      due to NF-GNB a short, fixed course (seven or eight days) of antibiotic therapy
      appears not to increase the risk of adverse clinical outcomes, and may reduce the
      emergence of resistant organisms, compared with a prolonged course (10 to 15
      days). However, for patients with VAP due to NF-GNB, there appears to be a higher
      risk of recurrence following short-course therapy. These findings do not differ
      from those of our previous review and are broadly consistent with current
      guidelines. There are few data from RCTs comparing durations of therapy in non
      ventilated patients with HAP, but on the basis of a single study, short-course
      (three-day) therapy for HAP appears not to be associated with worse clinical
      outcome, and may reduce the risk of subsequent infection or the emergence of
      resistant organisms when there is low probability of pneumonia according to the
      CPIS.

PMID- 26301603
TI  - Effect of Discontinuation of Antihypertensive Treatment in Elderly People on
      Cognitive Functioning--the DANTE Study Leiden: A Randomized Clinical Trial.
AB  - IMPORTANCE: Observational studies indicate that lower blood pressure (BP)
      increases risk for cognitive decline in elderly individuals. Older persons are at
      risk for impaired cerebral autoregulation; lowering their BP may compromise
      cerebral blood flow and cognitive function. OBJECTIVE: To assess whether
      discontinuation of antihypertensive treatment in older persons with mild
      cognitive deficits improves cognitive, psychological, and general daily
      functioning. DESIGN, SETTING, AND PARTICIPANTS: A community-based randomized
      clinical trial with a blinded outcome assessment at the 16-week follow-up was
      performed at 128 general practices in the Netherlands. A total of 385
      participants 75 years or older with mild cognitive deficits (Mini-Mental State
      Examination score, 21-27) without serious cardiovascular disease who received
      antihypertensive treatment were enrolled in the Discontinuation of
      Antihypertensive Treatment in Elderly People (DANTE) Study Leiden from June 26,
      2011, through August 23, 2013 (follow-up, December 16, 2013). Intention-to-treat
      analyses were performed from January 20 through April 11, 2014. INTERVENTIONS:
      Discontinuation (n=199) vs continuation (n=186) of antihypertensive treatment
      (allocation ratio, 1:1). MAIN OUTCOMES AND MEASURES: Change in the overall
      cognition compound score. Secondary outcomes included changes in scores on
      cognitive domains, the Geriatric Depression Scale-15, Apathy Scale, Groningen
      Activity Restriction Scale (functional status), and Cantril Ladder (quality of
      life). RESULTS: Compared with 176 participants undergoing analysis in the control
      (continuation) group, 180 in the intervention (discontinuation) group had a
      greater increase (95% CI) in systolic BP (difference, 7.36 [3.02 to 11.69] mm Hg;
      P=.001) and diastolic BP (difference, 2.63 [0.34 to 4.93] mm Hg; P=.03). The
      intervention group did not differ from the control group in change (95% CI) in
      overall cognition compound score (0.01 [-0.14 to 0.16] vs -0.01 [-0.16 to 0.14];
      difference, 0.02 [-0.19 to 0.23]; P=.84). The intervention and control groups did
      not differ significantly in secondary outcomes, including differences (95% CIs)
      in change in compound scores of the 3 cognitive domains (executive function, 
      0.07 [-0.29 to 0.15; P=.52], memory, 0.08 [-0.12 to 0.29; P=.43], and psychomotor
      speed, -0.85 [-1.72 to 0.02; P=.06]), symptoms of apathy (0.17 [-0.65 to 0.99;
      P=.68]) and depression (0.14 [-0.20 to 0.48; P=.41]), functional status (-0.72 [
      1.52 to 0.09; P=.08]), and quality-of-life score (-0.09 [-0.34 to 0.16; P=.46]).
      Adverse events were equally distributed. CONCLUSIONS AND RELEVANCE: In older
      persons with mild cognitive deficits, discontinuation of antihypertensive
      treatment did not improve cognitive, psychological, or general daily functioning
      at the 16-week follow-up. TRIAL REGISTRATION: trialregister.nl Identifier:
      NTR2829.

PMID- 26301607
TI  - The Care Transition in Plastic Surgery.

PMID- 26301605
TI  - MMP1, 2, 3, 7, and 9 gene polymorphisms and urinary cancer risk: a meta-analysis.
AB  - BACKGROUND: The matrix metalloproteinases (MMPs) are a family of highly
      conserved, metal-dependent proteolytic enzymes that play an important role in
      tumor invasion and metastasis. Many studies have been carried out on the
      association between polymorphisms in the MMP1, MMP2, MMP3, MMP7, and MMP9 genes
      and urinary cancer risk. However, the data from these published studies are
      conflicting and have low statistical power. METHODS: In this study, we performed
      a meta-analysis of 12 different publications from the PubMed and WanFang
      databases, published up to May 2015, to better assess the purported associations.
      Odds ratios (OR) and 95% confidence intervals (CI) were determined to reveal
      association strengths. RESULTS: Some significant associations were found. For the
      MMP1 -1607 1G/2G polymorphism, a negative association was identified for the 2G
      allele in bladder cancer (2G2G+2G1G vs. 1G1G: OR = 0.57, 95% CI = 0.36-0.93,
      pheterogeneity = 0.001) and renal cell carcinoma (2G1G vs. 1G1G: OR = 0.57, 95%
      CI = 0.39-0.82, pheterogeneity = 0.567). For the MMP2 -1306 C/T polymorphism,
      there was a negative association with the T allele for bladder cancer in the
      Asian population (TT+TC vs. CC: OR = 0.41, 95% CI = 0.18-0.94, pheterogeneity =
      0.195). For the MMP7 -181 A/G polymorphism, a decreased bladder cancer risk was
      found (G-allele vs. A-allele: OR = 0.81, 95% CI = 0.66-0.98, pheterogeneity
      =0.325). CONCLUSION: In summary, our study showed evidence that genetic
      polymorphisms in MMP1 for all populations, but only in the Asian population for
      MMP2 and MMP7, may protect against bladder cancer risk. Future studies with
      larger sample sizes are warranted to further evaluate these associations in more
      detail.

PMID- 26301608
TI  - Cryolipolysis: A Question of Scientific and Photographic Integrity.

PMID- 26301606
TI  - Measurement and validation of frailty as a predictor of outcomes in women
      undergoing major gynaecological surgery.
AB  - OBJECTIVE: Frailty is the loss of physical or mental reserve that impairs
      function, often in the absence of a defined comorbidity. Our aim was to determine
      whether a modified frailty index (mFI) correlates with morbidity and mortality in
      patients undergoing hysterectomy. DESIGN: Retrospective cohort study. SETTING:
      Hospitals across the USA participating in the National Surgical Quality
      Improvement Program (NSQIP). SAMPLE: Patients who underwent hysterectomy from
      2008 to 2012. METHODS: An mFI was calculated using 11 variables in NSQIP. The
      associations between mFI and morbidity and mortality were assessed. Model fit
      statistics (c-statistics) were utilised to evaluate the ability of mFI to
      distinguish outcomes. MAIN OUTCOME MEASURE: Wound infection, severe complications
      and mortality. RESULTS: A total of 66 105 patients were identified. Wound
      complications increased from 2.4% in patients with an mFI of zero to 4.8% in
      those with mFI >= 0.5 (P < 0.0001). Similarly, severe complications increased
      from 0.98% to 7.3% (P < 0.0001), overall complications rose from 3.7% to 14.5% (P
      < 0.0001) and mortality increased from 0.06% to 3.2% (P < 0.0001) for patients
      with a frailty index of zero compared with those with an index of >= 0.5. Versus
      chance, the goodness-of-fit c-statistics suggested that mFI increases the ability
      to detect wound complications by 11.4%, severe complications by 22.0% and overall
      complications by 11.0%. CONCLUSIONS: The mFI is easily reproducible from
      routinely collected clinical data and predictive of outcomes in patients
      undergoing hysterectomy. Frailty may be useful in the preoperative risk
      assessment of women undergoing gynaecological surgery. TWEETABLE ABSTRACT:
      Frailty may be useful in the preoperative risk assessment of women undergoing
      gynaecological surgery.

PMID- 26301609
TI  - The Extensor Digitorum Brevis Manus: Ganglion Surgeon Beware!

PMID- 26301610
TI  - Removing the Ambiguity from the Double Bubble.

PMID- 26301611
TI  - Memantine elicits spinal blockades of motor function, proprioception, and
      nociception in rats.
AB  - Although memantine blocks sodium currents and produces local skin anesthesia,
      spinal anesthesia with memantine is unknown. The purpose of the study was to
      evaluate the local anesthetic effect of memantine in spinal anesthesia and its
      comparison with a widely used local anesthetic lidocaine. After intrathecally
      injecting the rats with five doses of each drug, the dose-response curves of
      memantine and lidocaine were constructed. The potencies of the drugs and
      durations of spinal anesthetic effects on motor function, proprioception, and
      nociception were compared with those of lidocaine. We showed that memantine
      produced dose-dependent spinal blockades in motor function, proprioception, and
      nociception. On a 50% effective dose (ED50 ) basis, the rank of potency was
      lidocaine greater than memantine (P < 0.05 for the differences). At the
      equipotent doses (ED25 , ED50 , ED75 ), the block duration produced by memantine
      was longer than that produced by lidocaine (P < 0.05 for the differences).
      Memantine, but not lidocaine, displayed more sensory/nociceptive block than motor
      block. The preclinical data demonstrated that memantine is less potent than
      lidocaine, whereas memantine produces longer duration of spinal anesthesia than
      lidocaine. Memantine shows a more sensory-selective action over motor blockade. 

PMID- 26301612
TI  - Evidence for a magnitude effect in probability discounting with pigeons.
AB  - A magnitude effect in probability discounting is well established with humans, in
      which the value of a larger reward decreases more with uncertainty than the value
      of a smaller reward. We report 2 experiments that show that an analogous result
      is obtained with pigeons choosing between probabilistic food rewards in a 2
      component concurrent-chains procedure. In Experiment 1, the terminal links
      delivered large (4-s access to food) and small (2-s access to food) rewards with
      either 100% or 50% probability across components. Preference for the larger
      reward was greater in the 100% component. In Experiment 2, the terminal links
      delivered reinforcement on 100% or 50% of terminal links and the rewards were
      large (4-s access to food) or small (2-s access to food) across components.
      Preference for the 100% alternative was greater when rewards were large. In both
      experiments, results indicate that the value of the larger reward decreased more
      when its probability was 50% than the value of the smaller reward, confirming the
      magnitude effect, and were similar regardless of whether the food and no-food
      outcomes for the 50% terminal links were differentially signaled. Results were
      predicted by an extension of the cumulative decision model (Christensen & Grace,
      2010; Grace & McLean, 2006), which accounts for the effects of magnitude and
      probability on choice and can also explain the apparently contradictory results
      of prior research on the magnitude effect in delay discounting with pigeons. The
      model shows that a single process can account for delay and probability
      discounting in nonhumans, including the opposite effects of reward magnitude.

PMID- 26301613
TI  - Testing the limits of the Perruchet effect in choice response time tasks.
AB  - The Perruchet effect refers to a dissociation between trends in the conscious
      expectancy of an event and trends in the strength or the speed of responding to
      that event, which suggests that learned changes in the performance of a response
      may be automatic. Despite being consistently demonstrated in conditioning studies
      and simple reaction time (RT) tasks, mixed results have been found in the choice
      variant of the Perruchet effect, especially when expectancy and responding are
      measured concurrently (that is, on the same trial). The present experiments
      examined why the dissociation disappears when concurrent measurement is used by
      directly comparing trials on which expectancy is measured to trials on which
      expectancy is not measured. In Experiment 1, expectancy was measured on a
      randomly chosen 50% of trials, whereas expectancy was measured every fourth trial
      in Experiment 2. In both experiments, the Perruchet effect was weakened on trials
      that immediately followed an expectancy rating but was still clearly evident on
      other trials, suggesting that automatic facilitation of RT based on recent trial
      history is temporarily masked, rather than abolished, by a concurrent expectancy
      judgment. (PsycINFO Database Record 

PMID- 26301614
TI  - Enyne-2-pyrone [4 + 4]-Photocycloaddition: Sesquiterpene Synthesis and a Low
      Temperature Cope Rearrangement.
AB  - Intramolecular [4 + 4] photoreaction of 2-pyrones with a 1,3-enyne yields an
      unstable 1,2,5-cyclooctatriene product. Without a C4 pyrone substituent, 1,3
      hydrogen migration converts the allene to a 1,3-diene, with a skeleton related to
      dactylol. With methoxy substitution, Cope rearrangement yields a nine-membered
      ring fused to a cyclobutane. Both structures were confirmed by X-ray
      crystallography. The Cope rearrangement is apparently reversible, reforming the
      allene which undergoes a proton shift to the more stable 1,3-diene product. 

PMID- 26301615
TI  - Maintenance of Pain in Children With Functional Abdominal Pain.
AB  - OBJECTIVES: A significant proportion of children with functional abdominal pain
      develop chronic pain. Identifying clinical characteristics predicting pain
      persistence is important in targeting interventions. We examined whether child
      anxiety and/or pain-stooling relations were related to maintenance of abdominal
      pain frequency and compared the predictive value of 3 methods for assessing pain
      stooling relations (ie, diary, parent report, child report). METHODS: Seventy-six
      children (7-10 years old at baseline) who presented for medical treatment of
      functional abdominal pain were followed up 18 to 24 months later. Baseline
      anxiety and abdominal pain-stooling relations based on pain and stooling diaries
      and child- and parent questionnaires were examined in relationship to the
      persistence of abdominal pain frequency. RESULTS: Children's baseline anxiety was
      not related to persistence of pain frequency. Children who, however, displayed
      irritable bowel syndrome (IBS) symptoms at baseline maintained pain frequency at
      follow-up, whereas in children in whom there was no relationship between pain and
      stooling, pain frequency decreased. Pain and stool diaries and parent report of
      pain-stooling relations were predictive of pain persistence but child-report
      questionnaires were not. CONCLUSIONS: The presence of IBS symptoms in school-age
      children with functional abdominal pain appears to predict persistence of
      abdominal pain over time, whereas anxiety does not. Prospective pain and stooling
      diaries and parent report of IBS symptoms were predictors of pain maintenance,
      but child report of symptoms was not.

PMID- 26301617
TI  - Gastric Emptying of Liquids in Children.
AB  - OBJECTIVES: The present study was performed to determine normal values for
      gastric half-emptying time (t1/2GE) of liquids in healthy children. METHODS:
      Gastric emptying (GE) of a standardized test milk-drink measured with technetium
      scintigraphy and the C-acetate breath test (C-ABT) was compared in 19 children
      ages between 4 and 15 years with upper gastrointestinal symptoms. The C-ABT was
      subsequently used to determine normal values for GE of the same liquid test meal
      in 133 healthy children ages between 1 and 17 years. RESULTS: In the group of
      children with upper gastrointestinal symptoms, the results showed a significant
      correlation (r = 0.604, P = 0.0006) between t1/2GE measured with both techniques.
      In the group of healthy children, the results of t1/2GE showed that there was no
      influence of age, sex, weight, height, and body mass index on GE. CONCLUSIONS:
      Normal values for GE of a standardized test milk-drink in healthy children were
      determined with the C-ABT. This technique is considered reliable and is well
      accepted by the patients.

PMID- 26301616
TI  - Normal Growth and Essential Fatty Acid Status in Children With Intestinal Failure
      on Lipid Limitation.
AB  - OBJECTIVES: Lipid limitation, that is, <=1 g . kg-1 . day-1 of soy oil lipid
      emulsion (SOLE), has been suggested as a method to reduce the risk of intestinal
      failure (IF)-associated liver disease (IFALD). There are limited data as to the
      effects of this strategy on growth and essential fatty acid (EFA) status. The aim
      of the study was to assess growth, prevalence of cholestasis, and EFA deficiency
      in patients with IF who were provided daily SOLE at a dose <=1 g . kg-1 . day-1.
      METHODS: Medical records were retrospectively reviewed from 9 patients age 16
      months to 8 years who had IF requiring parenteral nutrition support for >12
      months. Parenteral nutrition supplied a mean of 53% of total energy (range 24%
      86%). RESULTS: Mean SOLE dose was 0.61 g . kg-1 . day-1 (range 0.4-0.81 g . kg-1
      . day-1). After 1 month of lipid limitation between 2011 and 2014, no patient
      developed IFALD as defined by a direct bilirubin >2 mg/dL. The median direct
      bilirubin was 0.1 mg/dL (range 0.075-0.85 mg/dL). No patient developed EFA
      deficiency as defined by a triene-to-tetraene ratio >0.2 (median 0.026, range
      0.017-0.076). Height z scores increased from mean of -2.568 (range -10.8 to
      0.878) to -0.484 (range -3.546 to 0.822). Weight z scores increased from mean of 
      1.412 (range -5.871 to 0.906) to -0.595 (range -2.178 to 0.926). CONCLUSIONS: In
      this case series, lipid limitation allowed normal growth while preventing the
      development of cholestasis and EFA deficiency.

PMID- 26301618
TI  - Repeated Screening Can Be Restricted to At-Genetic-Risk Birth Cohorts.
AB  - OBJECTIVES: Celiac disease (CD) is associated with tissue transglutaminase
      autoantibodies (tTGAs) in individuals carrying the human leukocyte antigen (HLA)
      risk haplotypes DQA1*05:01-DQB1*02:01 (DQ2) and/or DQA1*03:01-DQB1*03:02 (DQ8).
      The aim of the study was to identify CD in an HLA-genotyped birth cohort
      prospectively screened for CD. METHODS: In the initial screening, 13,860 HLA-DQ
      genotyped children were invited, of whom 3435/13,860 (25%) accepted
      participation. Of the 3435, 1620 (47%) carried DQ2 and/or DQ8, of whom 73 (4.5%)
      were tTGA positive assessed in radioligand-binding assays and 56 (3.5%) developed
      CD. At age 9 years, 13,024 children from the original cohort were re-invited to
      follow-up screening using the same study protocol and tTGA assays as in the first
      screening. Diagnosis of CD was confirmed by intestinal biopsy in children with
      persistent tTGA. RESULTS: In the follow-up screening, 1910/4077 (46.8%) carried
      DQ2 and/or DQ8, of whom 79/1910 (4.1%) were persistently tTGA positive and
      72/1907 (3.8%) developed CD. Only 1/2167 (0.05%) child without HLA risk was IgG
      tTGA positive, but did not have CD. Of the 980/1910 (51%) children carrying DQ2
      and/or DQ8 who were already screened at 3 years of age, 30/979 (3.1%) were
      diagnosed as new patients at 9 years of age, compared with 42/928 (4.5%) children
      who did not participate in the initial screening (P = 0.094). CONCLUSIONS:
      Screening for CD can be restricted to children carrying HLA-DQ2 and/or DQ8.
      Repeated screening using tTGA is necessary to identify new patients by 9 years of
      age. These findings may be relevant when considering implementing screening of
      the general population.

PMID- 26301619
TI  - Rhodium-Catalyzed Asymmetric 1,4-Addition of alpha,beta-Unsaturated Imino Esters
      Using Chiral Bicyclic Bridgehead Phosphoramidite Ligands.
AB  - A chiral bicyclic bridgehead phosphoramidite (briphos) prepared from 1
      aminoindane is a highly efficient and selective ligand for rhodium(I)-catalyzed
      asymmetric 1,4-addition of arylboronic acids to alpha,beta-unsaturated N,N
      dimethyl-sulfamoyl imino esters at ambient temperature. This transformation
      provides a new class of chiral (Z)-gamma,gamma-diaryl-alpha,beta-dehydroamino
      esters with excellent yield and enantioselectivity. 

PMID- 26301620
TI  - Trigeminal nerve stimulation (TNS) for fibromyalgia: A proof-of-concept trial.

PMID- 26301621
TI  - Nearly one in five adults with active epilepsy lives alone based on findings from
      the 2010 and 2013 US National Health Interview Surveys. US Centers for Disease
      Control and Prevention, Epilepsy Program.

PMID- 26301622
TI  - The MCT-ketogenic diet as a treatment option in refractory childhood epilepsy: A
      prospective study with 2-year follow-up.
AB  - The present study assessed the long-term (i.e., 24months) efficacy of the
      ketogenic diet (KD) as an add-on therapy in children with refractory epilepsy,
      with focus on seizure frequency, seizure severity, and tolerability. Most
      patients were treated with the MCT-diet. At one and two years, 33% and 23%,
      respectively, of the 48 included patients were still on the KD. After three
      months, one year, and two years of treatment, 16.7% of the patients were
      responders. The highest responder rate (i.e., 22.9%) was seen at six and nine
      months of treatment. Of the fifteen patients with seizure clusters during
      baseline, 60% were responders after three months when looking at cluster
      reduction and most of them were not responders for the total seizure frequency.
      From three months of treatment onwards, most of the patients had a relevant
      decrease in seizure severity which was mainly related to the most severe seizure
      type. Gastrointestinal dysfunction was often reported, especially in the first
      six weeks of treatment. Growth deceleration was present in 30% of the patients,
      and weight reduction in 15%. Improved arousal was mentioned in 30% of patients.
      No patients developed ECG abnormalities or kidney stones. Increase in lipid
      profile was rare. The KD is an effective therapy for children with therapy
      resistant epilepsy. Effectiveness is reflected in the reduction of seizure
      frequency as well as in the reduction of seizure severity. After 6months of
      treatment, it is obvious which patients are responders and tolerate the treatment
      well. Most of these patients will continue to benefit from the KD for a longer
      time. Long-term use of the diet was well tolerated. 

PMID- 26301623
TI  - Dosimetric accuracy of a treatment planning system for actively scanned proton
      beams and small target volumes: Monte Carlo and experimental validation.
AB  - This study was performed to evaluate the accuracy of a commercial treatment
      planning system (TPS), in optimising proton pencil beam dose distributions for
      small targets of different sizes (5-30 mm side) located at increasing depths in
      water. The TPS analytical algorithm was benchmarked against experimental data and
      the FLUKA Monte Carlo (MC) code, previously validated for the selected beam-line.
      We tested the Siemens syngo((r)) TPS plan optimisation module for water cubes
      fixing the configurable parameters at clinical standards, with homogeneous target
      coverage to a 2 Gy (RBE) dose prescription as unique goal. Plans were delivered
      and the dose at each volume centre was measured in water with a calibrated PTW
      Advanced Markus((r)) chamber. An EBT3((r)) film was also positioned at the
      phantom entrance window for the acquisition of 2D dose maps. Discrepancies
      between TPS calculated and MC simulated values were mainly due to the different
      lateral spread modeling and resulted in being related to the field-to-spot size
      ratio. The accuracy of the TPS was proved to be clinically acceptable in all
      cases but very small and shallow volumes. In this contest, the use of MC to
      validate TPS results proved to be a reliable procedure for pre-treatment plan
      verification.

PMID- 26301624
TI  - Global Noncommunicable Disease Research: Opportunities and Challenges.

PMID- 26301625
TI  - Decadally cycling soil carbon is more sensitive to warming than faster-cycling
      soil carbon.
AB  - The response of soil organic carbon (SOC) pools to globally rising surface
      temperature crucially determines the feedback between climate change and the
      global carbon cycle. However, there is a lack of studies investigating the
      temperature sensitivity of decomposition for decadally cycling SOC which is the
      main component of total soil carbon stock and the most relevant to global change.
      We tackled this issue using two decadally (13) C-labeled soils and a much
      improved measuring system in a long-term incubation experiment. Results indicated
      that the temperature sensitivity of decomposition for decadally cycling SOC (>23
      years in one soil and >55 years in the other soil) was significantly greater than
      that for faster-cycling SOC (<23 or 55 years) or for the entire SOC stock.
      Moreover, decadally cycling SOC contributed substantially (35-59%) to the total
      CO2 loss during the 360-day incubation. Overall, these results indicate that the
      decomposition of decadally cycling SOC is highly sensitive to temperature change,
      which will likely make this large SOC stock vulnerable to loss by global warming
      in the 21st century and beyond. 

PMID- 26301627
TI  - Chromanyl-isoxazolidines as Antibacterial agents: Synthesis, Biological
      Evaluation, Quantitative Structure Activity Relationship, and Molecular Docking
      Studies.
AB  - Regio- and stereoselective 1,3-dipolar cycloadditions of C-(chrom-4-one-3-yl)-N
      phenylnitrones (N) with different mono-substituted, disubstituted, and cyclic
      dipolarophiles were carried out to obtain substituted N-phenyl-3'-(chrom-4-one-3
      yl)-isoxazolidines (1-40). All the synthesized compounds were assayed for their
      in vitro antibacterial activity and display significant inhibitory potential; in
      particular, compound 32 exhibited good inhibitory activity against Salmonella
      typhymurium-1 & Salmonella typhymurium-2 with minimum inhibitory concentration
      value of 1.56 MUg/mL and also showed good potential against methicillin-resistant
      Staphylococcus aureus with minimum inhibitory concentration 3.12 MUg/mL.
      Quantitative structure activity relationship investigations with stepwise
      multiple linear regression analysis and docking simulation studies have been
      performed for validation of the observed antibacterial potential of the
      investigated compounds for determination of the most important parameters
      regulating antibacterial activities. 

PMID- 26301626
TI  - Optimization of Novel Indazoles as Highly Potent and Selective Inhibitors of
      Phosphoinositide 3-Kinase delta for the Treatment of Respiratory Disease.
AB  - Optimization of lead compound 1, through extensive use of structure-based design
      and a focus on PI3Kdelta potency, isoform selectivity, and inhaled PK properties,
      led to the discovery of clinical candidates 2 (GSK2269557) and 3 (GSK2292767) for
      the treatment of respiratory indications via inhalation. Compounds 2 and 3 are
      both highly selective for PI3Kdelta over the closely related isoforms and are
      active in a disease relevant brown Norway rat acute OVA model of Th2-driven lung
      inflammation. 

PMID- 26301629
TI  - Series of Carbazole-Pyrimidine Conjugates: Syntheses and Electronic,
      Photophysical, and Electrochemical Properties.
AB  - A series of carbazole-pyrimidine conjugates 1-17 were synthesized by Pd-catalyzed
      cross-coupling, oxidation, and nucleophilic aromatic substitution reactions. In 1
      17, the carbazole moieties are connected at the 4,6-positions of the pyrimidine
      ring either directly or via ethynylene or vinylene spacers, and various electron
      donating or electron-withdrawing substituents are introduced at the 2-position of
      the pyrimidine ring. The effects of structural variations on the electronic,
      photophysical, and electrochemical properties of 1-17 were comprehensively
      investigated. Compounds 1-17 exhibit intramolecular charge-transfer (ICT) states,
      which essentially lead to moderate-to-strong fluorescence emission with large
      Stokes shifts depending on the solvent polarity. These compounds tend to show
      significant changes in optical and fluorescence properties upon addition of
      trifluoroacetic acid. The electron-accepting ability of these compounds can be
      tuned by both substituents on the pyrimidine moiety and spacers. The ethynylene
      spacer lowers both the HOMO and LUMO levels, while the vinylene spacer elevates
      the HOMO level and lowers the LUMO level. The X-ray crystal structures of 3, 6,
      11, and 14 are also disclosed. 

PMID- 26301628
TI  - Maternal serum osteocalcin at 11-14 weeks of gestation in gestational diabetes
      mellitus.
AB  - BACKGROUND: Recent studies support that osteocalcin (OC), apart from its skeletal
      role, is implicated in glucose homoeostasis. Aims of this study were to examine
      the first-trimester maternal serum concentrations of OC in pregnancies that
      developed gestational diabetes mellitus (GDM) and to create a first-trimester
      prediction model for GDM. DESIGN: Case-control study in a prospective cohort of
      pregnant women. Maternal serum levels of OC were measured in 40 cases that
      developed GDM and 94 unaffected controls. First-trimester biophysical parameters,
      biochemical indices, maternal-pregnancy characteristics, and OC concentrations
      were assessed in relation to GDM occurrence. RESULTS: In the GDM group, first
      trimester OC serum levels were increased compared to the control group (mean =
      8.81 ng/mL, SD = 2.59 vs. mean = 7.34 ng/ml, SD = 3.04, P = 0.0058). Osteocalcin
      was independent of first-trimester biophysical and biochemical indices.
      Osteocalcin alone (OR = 1.21, CI: 1.02-1.43, P = 0.023) was a significant
      predictor of GDM [Model R(2) = 0.04, area under the curve (AUC) = 0.61, CI: 0.55
      0.72, P < 0.001]. The combination of maternal and pregnancy characteristics with
      OC resulted in an improved prediction model for GDM (Model R(2) = 0.21, AUC =
      0.80, CI: 0.71-0.88, P < 0.001). The combined model yields a sensitivity of 72.2%
      for 25% false-positive rate. CONCLUSIONS: First-trimester maternal serum levels
      of OC are increased in GDM pregnancies. Osteocalcin combined with maternal and
      pregnancy characteristics provides an effective screening for GDM at 11-14 weeks.

PMID- 26301630
TI  - Phosphorylation at the N-terminal finger subdomain of a viral RNA-dependent RNA
      polymerase.
AB  - The RNA-dependent RNA polymerase (RdRP) of the Hepatitis C virus (HCV), named
      NS5B, is phosphorylated by the cellular protein kinase C-related kinase 2 (PRK2)
      at two serine residues (Ser29 and Ser42) of the finger subdomain (genotype 1b).
      Herein, using bioinformatics, we selected four potential phosphorylation residues
      (Ser46, Ser76, Ser96 and Ser112) of NS5B (genotype 2a) for study. Whereas the
      NS5B Ser46D and Ser76D substitutions seemed to improve polymerase activity, the
      Ser96D mutation decreased colony formation efficiency. Active WT NS5B was
      utilized in in vitro kinase assays, and phosphopeptides were analyzed by mass
      spectrometry. Interestingly, the data indicated that both the NS5B Ser29 and
      Ser76 residues resulted phosphorylated. Thus, as Ser76 is absolutely conserved
      across HCV genotypes, our results confirmed the relevance of these sites for both
      genotypes and suggested that Ser76 becomes phosphorylated by a cellular kinase
      different from PRK2. By molecular dynamic simulations, we show that new
      interactions between space-adjacent amino acid chains could be established by the
      presence of a di-anionic phosphate group on the analyzed serines to possibly
      modify RNA polymerase activity. Together, our data present novel evidence on the
      complex regulation at the finger subdomain of HCV NS5B via phosphorylation.

PMID- 26301631
TI  - Structural analysis of CXCR4 - Antagonist interactions using saturation-transfer
      double-difference NMR.
AB  - CXCR4 is a GPCR involved in leukocyte trafficking. Small molecule antagonists of
      the receptor may treat inflammatory disease, cancer and HIV. Here we probe the
      binding of a tetrahydroisoquinoline-based antagonist (TIQ-10) to CXCR4 using
      saturation transfer double-difference (STDD) NMR. STDD spectra were acquired
      using extracts from Chinese Hamster Ovary cells expressing membrane-embedded
      CXCR4. The experiments demonstrate competitive binding between TIQ-10 and
      established antagonists and provide the TIQ-10 - CXCR4 binding epitope. Molecular
      modeling of TIQ-10 into the binding pocket provides a pose consistent with STDD
      derived interactions. This study paves the way for future investigations of GPCR
      ligand interactions in a biological milieu for use in chemical biology,
      biochemistry, structural biology, and rational drug design. 

PMID- 26301632
TI  - PRDX1 is involved in palmitate induced insulin resistance via regulating the
      activity of p38MAPK in HepG2 cells.
AB  - Studies have identified that type 2 diabetes mellitus (T2DM) patients displayed
      higher levels of plasma peroxiredoxin1(PRDX1) than non-diabetics. However, the
      impact of PRDX1 on insulin resistance and the underlying mechanism remains
      totally unknown. Here, we investigated the influence of PRDX1 on hepatic insulin
      resistance. We showed that the protein and mRNA levels of PRDX1 were
      significantly elevated under insulin-resistant conditions. In addition, we showed
      that interference of PRDX1 ameliorated palmitate-induced insulin resistance in
      HepG2 cells, which was indicated by elevated phosphorylation of protein kinase B
      (AKT) and of glycogen synthase kinase-3 (GSK3beta). Furthermore, the expression
      of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase),
      two key gluconeogenic enzymes, were down-regulated following PRDX1 depletion.
      Accordingly, glucose uptake was suppressed in PRDX1-interferred HepG2 cells. In
      addition, Over-expression of PRDX1 enhanced PA-induced insulin resistance in
      HepG2 cells. Moreover, we found that knocking down PRDX1 improves insulin
      sensitivity and decreased the activation of p38 mitogen-activated protein kinase
      (p38MAPK). Our results demonstrate that PRDX1 can induce hepatic insulin
      resistance by activating p38MAPK signaling and identifies potential targets for
      new treatments. 

PMID- 26301633
TI  - A light-switchable bidirectional expression module allowing simultaneous
      regulation of multiple genes.
AB  - Several light-regulated genetic circuits have been applied to spatiotemporally
      control transgene expression in mammalian cells. However, simultaneous regulation
      of multiple genes using one genetic device by light has not yet been reported. In
      this study, we engineered a bidirectional expression module based on LightOn
      system. Our data showed that both reporter genes could be regulated at defined
      and quantitative levels. Simultaneous regulation of four genes was further
      achieved in cultured cells and mice. Additionally, we successfully utilized the
      bidirectional expression module to monitor the expression of a suicide gene,
      showing potential for photodynamic gene therapy. Collectively, we provide a
      robust and useful tool to simultaneously control multiple genes expression by
      light, which will be widely used in biomedical research and biotechnology. 

PMID- 26301635
TI  - Carotid intima media thickness can predict coronary artery disease.

PMID- 26301634
TI  - Network Modules of the Cross-Species Genotype-Phenotype Map Reflect the Clinical
      Severity of Human Diseases.
AB  - Recent advances in genome sequencing techniques have improved our understanding
      of the genotype-phenotype relationship between genetic variants and human
      diseases. However, genetic variations uncovered from patient populations do not
      provide enough information to understand the mechanisms underlying the
      progression and clinical severity of human diseases. Moreover, building a high
      resolution genotype-phenotype map is difficult due to the diverse genetic
      backgrounds of the human population. We built a cross-species genotype-phenotype
      map to explain the clinical severity of human genetic diseases. We developed a
      data-integrative framework to investigate network modules composed of human
      diseases mapped with gene essentiality measured from a model organism. Essential
      and nonessential genes connect diseases of different types which form clusters in
      the human disease network. In a large patient population study, we found that
      disease classes enriched with essential genes tended to show a higher mortality
      rate than disease classes enriched with nonessential genes. Moreover, high
      disease mortality rates are explained by the multiple comorbid relationships and
      the high pleiotropy of disease genes found in the essential gene-enriched
      diseases. Our results reveal that the genotype-phenotype map of a model organism
      can facilitate the identification of human disease-gene associations and predict
      human disease progression. 

PMID- 26301636
TI  - Recurrent multiform Takotsubo cardiomyopathy in a patient with epilepsy: Broken
      heart or brain?

PMID- 26301637
TI  - Successful endovascular treatment with a cutting balloon for traumatic
      obstruction of an external iliac artery in a young male.

PMID- 26301638
TI  - Impact of antibiotics on arterial blood pressure in a patient with resistant
      hypertension - A case report.

PMID- 26301639
TI  - New polyurethane covered stent with low profile for treatment of a large aneurysm
      after Left Anterior Descending artery stenting: First experience.

PMID- 26301641
TI  - Reply to "The relation between flow mediated dilation and atrial fibrillation" by
      S. Balta: Refers to Sevket Balta, MD et al.

PMID- 26301640
TI  - Exercise programs for LVAD supported patients: A snapshot from the ESC affiliated
      countries.
AB  - BACKGROUND: To contribute to the protocol development of exercise training in
      LVAD supported patients by reviewing the exercise programs for those patients in
      the ESC affiliated countries. METHODS: A subset of data from 77 (26 countries)
      LVAD implanting centers that participated in the Extra-HF survey (170 centers)
      was analyzed. RESULTS: Of the 77 LVAD implanting centers, 45 (58%) reported to
      have a functioning exercise training program (ETP) for LVAD patients. In 21 (47%)
      of the 45 ETP programs in LVAD implanting centers, patients begin their ETP
      during their in-hospital post-operative recovery period. Most centers (71%) have
      an early post-discharge program for their patients, and 24% of the centers offer
      a long-term maintenance program. The professionals involved in the ETPs are
      mainly physiotherapists (73%), psychologists, cardiac rehab nurses (22%), or
      cardiologists specialized in rehabilitation (22%). Not all programs include the
      treating cardiologist or surgeons. Most of the ETPs (84%) include aerobic
      endurance training, mostly cycling (73%), or walking (62%) at low intensity
      intervals. Some programs apply resistance training (47%), respiratory muscle
      training (55%), or balance training (44%). Reasons for the absence of ETPs are
      referral of patients to another center (14 centers) and lack of resources (11
      centers). CONCLUSION: There is a great variance in ETPs in LVAD implanting
      centers. Not all the implanting centers have an ETP, and those that do have
      adopted a local protocol. Clear guidance on ETP supplied by LVAD implanting
      centers to LVAD supported patients and more evidence for optimal modalities are
      needed.

PMID- 26301642
TI  - Takotsubo revisited.

PMID- 26301643
TI  - An unexpected cause of cardiomyopathy revealed by arrhythmias and conduction
      disorders in an athlete.

PMID- 26301644
TI  - In-hospital management of acute heart failure: Practical recommendations and
      future perspectives.
AB  - Acute heart failure (AHF) represents the first reason for hospitalization in the
      elderly and despite therapeutic advances, remains a syndrome with significant
      morbidity and dismal prognosis. Hospitalization for AHF, on the other hand, is
      the single most important contributor to the huge financial burden related to HF.
      As a result, there is a significant unmet need for more effective in-hospital
      management of patients with AHF in order to improve outcomes, reduce readmission
      rate and alleviate the socioeconomic burden of the syndrome. The in-hospital
      management of AHF patients may schematically be divided into three phases, an
      early phase of intensive management of congestion and/or hypoperfusion, an
      intermediate phase of transition to oral life-saving medications and a late phase
      of discharge and transition to outpatient management. In the present paper, we
      attempt to provide a concise and practical roadmap for each of the above phases,
      focusing mainly on defining clinical and laboratory criteria for the evaluation
      of patients and on describing therapeutic algorithms that summarize the available
      evidence and guidelines. In addition, we highlight some key open issues that need
      to be addressed by future research. 

PMID- 26301646
TI  - An unusual case of left ventricle noncompaction.

PMID- 26301645
TI  - Comparison of combination therapy of high-dose oral N-acetylcysteine and
      intravenous sodium bicarbonate hydration with individual therapies in the
      reduction of Contrast-induced Nephropathy during Cardiac Catheterisation and
      Percutaneous Coronary Intervention (CONTRAST): A multi-centre, randomised,
      controlled trial.
AB  - INTRODUCTION: N-acetylcysteine (NAC) and sodium bicarbonate (SOB) therapies may
      prevent contrast-induced nephropathy (CIN). However, the efficacy of using
      combination over individual therapies was not established, and there was no large
      randomised study comparing abbreviated SOB therapy with conventional sustained
      saline pre-hydration with oral NAC. METHODS: In a multi-centre, open-label,
      randomised, controlled trial (NCT00497328), we prospectively enrolled 548
      patients with at least moderate renal impairment undergoing cardiac
      catheterisation with or without percutaneous coronary intervention. Patients were
      randomly assigned to 3 groups: 1) NAC: 154 mEq/L sustained sodium chloride regime
      (1 mL/kg/h 12 h before, during and 6h after the procedure) with oral NAC at 1.2g
      bid for 3 days (n=185); 2) SOB: 154 mEq/L abbreviated SOB regime at 3 mL/kg/h 1h
      before the procedure, and 1 mL/kg/h during and 6h after the procedure (n=182);
      and 3) COM: combination of abbreviated SOB regime and oral NAC (n=181). The
      primary end point was incidence of CIN. The secondary end points were rise in
      serum creatinine, hospitalisation duration, haemodialysis, morbidity and
      mortality within 30 days. RESULTS: The 3 groups had similar baseline
      characteristics: age 68 +/- 10 years, 76% male, 48% diabetic and baseline
      glomerular filtration rate (GFR) 47.7 +/- 13.0 mL/min. There were 41 (8.8%)
      patients with GFR<30. The CIN incidences were NAC 6.5%, SOB 12.8% and COM 10.6%.
      The COM regimen was not superior to either the NAC (relative risk (RR)=1.61, 95%
      confidence interval (CI): 0.76 to 3.45, p=0.225) or SOB (RR=0.83, 95% CI: 0.44 to
      1.56, p=0.593) regimens. The CIN incidence was lower in the NAC group than the
      SOB group (adjusted odds ratio (OR)=0.40, 95% CI: 0.17 to 0.92; p=0.032).
      Multivariate analysis showed contrast volume (OR=1.99, 95% CI: 1.33 to 2.96,
      p<0.001 per 100mL), female (OR=2.47, 95% CI: 1.22 to 5.00, p=0.012) and diabetes
      (OR=2.03, 95% CI: 1.03 to 3.99, p=0.041) were independent risk predictors. There
      were no differences in the secondary outcomes among the 3 groups. CONCLUSION: The
      combination regimen was not superior to individual regimens in preventing CIN in
      patients with baseline renal impairment. There was a trend suggesting that the 12
      hour sustained sodium chloride pre-hydration regimen was more protective than the
      1-hour abbreviated SOB regimen.

PMID- 26301647
TI  - ATF3: A promotion effect or a inhibition effect in cardiac maladaptive
      remodeling.

PMID- 26301648
TI  - Safety and efficacy of ezetimibe: A meta-analysis.
AB  - BACKGROUND: The addition of ezetimibe to statin therapy has been widely
      demonstrated to significantly reduce low-density lipoprotein cholesterol levels.
      However, the efficacy of ezetimibe in reducing CV events and its safety has been
      less investigated. The aim of the current meta-analysis was to report efficacy
      and safety of ezetimibe from randomized clinical trials. METHODS: Randomized
      clinical trials with a follow-up of at least 24 weeks, enrolling more than 200
      patients, comparing ezetimibe versus placebo or ezetimibe plus another
      hypolipidemic agent versus the same hypolipidemic drug alone and reporting at
      least one event among all-cause and CV mortality, myocardial infarction (MI),
      stroke and new onset of cancer were included in the analysis. RESULTS: 7 trials
      enrolling 31,048 patients (median follow-up 34.1 +/- 26.3 months; 70% women; mean
      age 61 +/- 8 years) were included in the analysis. Compared to control therapy,
      ezetimibe significantly reduced the risk of MI by 13.5% (RR: 0.865, 95% CI: 0.801
      to 0.934, p<0.001) and the risk of any stroke by 16.0% (RR: 0.840, 95% CI: 0.744
      to 0.949, p=0.005), without any effect on all-cause and CV mortality (RR: 1.003,
      95% CI: 0.954 to 1.055, p=0.908; RR: 0.958, 95% CI: 0.879 to 1.044, p=0.330;
      respectively) and risk of new cancer (RR: 1.040, 95% CI: 0.965 to 1.120,
      p=0.303). CONCLUSIONS: Ezetimibe significantly reduces the risk of MI and stroke
      without any effect on all-cause and CV mortality and risk of cancer.

PMID- 26301649
TI  - DPP-4 inhibitors: A promising feasible therapeutic approach for myocardial
      ischemia-reperfusion injury.

PMID- 26301650
TI  - No evidence for increased prostate cancer risk among calcium channel blockers
      user.

PMID- 26301651
TI  - Combined effects of accelerometer-assessed physical activity and dietary behavior
      on all-cause mortality in a national prospective cohort study.

PMID- 26301652
TI  - First-in-human transcatheter aortic valve-in-valve replacement with the SAPIEN 3
      heart valve.

PMID- 26301653
TI  - Rare cardiac involvement in adrenal carcinoma.

PMID- 26301654
TI  - In-hospital outcomes and long-term mortality according to sex and management
      strategy in acute myocardial infarction. Insights from the French ST-elevation
      and non-ST-elevation Myocardial Infarction (FAST-MI) 2005 Registry.
AB  - BACKGROUND: The early mortality of acute myocardial infarction (AMI) has
      dramatically decreased in the recent past. Whether the previously reported sex
      disparities in use of invasive strategies (IS) persist and translate into
      differences in outcomes deserves to be examined. METHODS: We used the data from a
      nationwide French prospective multicentre registry from 3,670 AMI patients (1155
      women (31.5%), 2515 men (68.5%)) recruited in 223 centres in 2005 and followed-up
      for 5 years. We examined in-hospital outcomes and 5-year mortality in patients
      categorized according to sex and use of IS (i.e. coronary angiography during the
      hospitalisation with a view to revascularisation). RESULTS: IS was less
      frequently used in women than in men (adjusted OR=0.66; 95% CI: 0.52-0.85),
      regardless of the type of AMI, age group or risk category, while use of
      recommended medications was similar at 48 hours and discharge. In-hospital
      mortality did not differ according to sex, whatever the age group and use of an
      IS. At 5 years, overall and post-discharge mortality were similar in men and
      women. However, IS was associated with lower 5-year mortality in women (HR=0.66;
      95% CI: 0.51-0.86) as in men (HR=0.48; 95% CI: 0.38-0.60) and there was no sex
      strategy interaction. CONCLUSIONS: Invasive strategy remains less frequently used
      in women than in men, yet is associated with improved five-year survival
      irrespective of sex. Whether reducing the sex gap in its use would translate into
      a higher survival in women remains an open question. CLINICAL TRIAL REGISTRATION:
      NCT 00673036.

PMID- 26301656
TI  - Cardiac adipose tissue: Distinction between epicardial and pericardial fat
      remains important!

PMID- 26301655
TI  - Therapeutic efficacy after percutaneous transluminal pulmonary angioplasty in
      CTEPH with and without clotting disorder according to anti-cardiolipin antibody.

PMID- 26301657
TI  - Risk stratification for secondary prevention with ticagrelor and aspirin: A
      closer look to patient subsets from the PEGASUS-TIMI 54 trial.

PMID- 26301658
TI  - A new entity in an immunosuppressive patient: Giant reverse kissing vegetation.

PMID- 26301659
TI  - In vivo effect of LASSBio-785, a lipid-lowering and anti-inflammatory agent, on
      cardiac Ca(2+)-ATPases from hypercholesterolemic rats.

PMID- 26301660
TI  - A bridge over troubled water: Functional assessment of a myocardial bridge.

PMID- 26301661
TI  - A novel mutation of TGFBR2 causing Loeys-Dietz syndrome complicated with
      pregnancy-related fatal cervical arterial dissections.

PMID- 26301662
TI  - Antidepressant use is associated with reduced myocardial mIBG uptake in CAD
      patients.

PMID- 26301663
TI  - Lifestyle behaviour and lifetime incidence of heart diseases.
AB  - OBJECTIVES: Investigate the relationship of some behavioural characteristics of a
      male population with lifetime incidence of heart diseases. MATERIAL AND METHODS:
      In the Italian Rural Areas of the Seven Countries Study of Cardiovascular
      Diseases, 1677 heart disease-free men aged 40-59 years were followed up during 50
      years for lifetime incidence of heart disease up to the age of 90 years. They
      were classified as coronary heart disease (CHD) and heart diseases of uncertain
      etiology (HDUE). Baseline cigarette smoking habits (non-smokers and ex-smokers,
      moderate smokers, heavy smokers), physical activity (sedentary, moderate,
      vigorous) and eating habits (non-Mediterranean Diet, Prudent Diet and
      Mediterranean Diet) were related to incidence of heart disease. RESULTS:
      Incidence of CHD and HDUE up to the age of 90 years was 28.8 and 17.7%,
      respectively. Univariate and multivariate analyses showed strong association of
      behavioural characteristics with CHD incidence, but not with HDUE incidence. Cox
      proportional hazard rates for CHD were 1.45 (95% confidence intervals, CI: 1.11
      1.90) for heavy smokers versus non-smokers; 0.67 (CI 0.50-0.89) for vigorous
      activity versus sedentary habits and 0.62 (CI 0.47-0.83) for Mediterranean Diet
      versus non-Mediterranean Diet. Combining CHD cases with HDUE cases made the
      predictive picture similar to that of CHD. When some basic risk factors were
      added to the model results remained substantially unaltered, despite the
      existence of some correlations of behaviours with risk factors. CONCLUSIONS:
      Behavioural factors including cigarette smoking, physical activity and diet are
      strong predictors of lifetime incidence of common heart diseases even adding
      other traditional risk factors.

PMID- 26301664
TI  - An educational intervention to help medical students achieve accurate and
      consistent measurement of longitudinal myocardial strain on transthoracic
      echocardiogram.

PMID- 26301666
TI  - Assessment of risk factors for bleeding in Japanese patients with non-valvular
      atrial fibrillation receiving warfarin treatment: A subanalysis of the J-RHYTHM
      Registry.

PMID- 26301665
TI  - Etiologies, clinical features and outcome of cardiac arrest in HIV-infected
      patients.
AB  - BACKGROUND: Compared to many other cardiovascular diseases, there is a paucity of
      data on the characteristics of successfully resuscitated cardiac arrest (CA)
      patients with human immunodeficiency virus (HIV) infection. We investigated
      causes, clinical features and outcome of these patients, and assessed the
      specific burden of HIV on outcome. METHODS: Retrospective analysis of HIV
      infected patients admitted to 20 French ICUs for successfully resuscitated CA
      (2000-2012). Characteristics and outcome of HIV-infected patients were compared
      to those of a large cohort of HIV-uninfected patients admitted after CA in the
      Cochin Hospital ICU during the same period. RESULTS: 99 patients were included
      (median CD4 lymphocyte count 233/mm(3), viral load 43 copies/ml). When compared
      with the control cohort of 1701 patients, HIV-infected patients were younger,
      with a predominance of male, a majority of in-hospital CA (52%), and non
      shockable initial rhythm (80.8%). CA was mostly related to respiratory cause
      (n=36, including 23 pneumonia), cardiac cause (n=33, including 16 acute
      myocardial infarction), neurologic cause (n=8) and toxic cause (n=5). CA was
      deemed directly related to HIV infection in 18 cases. Seventy-one patients died
      in the ICU, mostly for care withdrawal after post-anoxic encephalopathy. After
      propensity score matching, ICU mortality was not significantly affected by HIV
      infection. Similarly, HIV disease characteristics had no impact on ICU outcome.
      CONCLUSIONS: Etiologies of CA in HIV-infected patients are miscellaneous and
      mostly not related to HIV infection. Outcome remains bleak but is similar to
      outcome of HIV-negative patients.

PMID- 26301667
TI  - Relation between elevated blood urea nitrogen, clinical features or
      comorbidities, and clinical outcome in patients hospitalized for acute heart
      failure syndromes.

PMID- 26301668
TI  - Prognostic value of computed tomography based SYNTAX score in coronary artery
      disease.

PMID- 26301669
TI  - Recurrent spontaneous coronary artery dissection: Unexpected evolution and major
      role of emotional stress.

PMID- 26301670
TI  - Basic principles of survival analysis with composite endpoints: Why you must use
      the "first" event, not the "worst" event.

PMID- 26301671
TI  - Percutaneous mitral valve repair (PMVR) in a patient with recurrence of mitral
      regurgitation 17 years after surgical reconstruction.

PMID- 26301672
TI  - Predictors of high-risk coronary artery disease detected by coronary computed
      tomographic angiography in diabetic patients without known coronary artery
      disease.

PMID- 26301673
TI  - Ventricular tachycardia with right bundle branch block morphology in
      arrhythmogenic right ventricular cardiomyopathy.

PMID- 26301674
TI  - Formation of the inflammasome during cardiac allograft rejection.

PMID- 26301675
TI  - Near-miss of ruptured myocardial infarction and catheter ablation injury
      associated with lethal cardiac tamponade.

PMID- 26301676
TI  - Percutaneous coronary intervention with RACER renal stents in very large diameter
      coronary arteries.

PMID- 26301677
TI  - Catheter-based renal denervation for resistant hypertension: Twenty-four month
      results of the EnligHTN I first-in-human study using a multi-electrode ablation
      system.
AB  - BACKGROUND: Long term safety and efficacy data of multi-electrode ablation system
      for renal denervation (RDN) in patients with drug resistant hypertension (dRHT)
      are limited. METHODS AND RESULTS: We studied 46 patients (age: 60 +/- 10 years,
      4.7 +/- 1.0 antihypertensive drugs) with drug resistant hypertension (dRHT).
      Reduction in office BP at 24 months from baseline was -29/-13 mmHg, while the
      reduction in 24-hour ambulatory BP and in home BP at 24 months were -13/-7 mmHg
      and -11/-6 mmHg respectively (p<0.05 for all). A correlation analysis revealed
      that baseline office and ambulatory BP were related to the extent of office and
      ambulatory BP drop. Apart from higher body mass index (33.3 +/- 4.7 vs 29.5 +/-
      6.2 kg/m(2), p<0.05), there were no differences in patients that were RDN
      responders defined as >=10 mmHg decrease (74%, n=34) compared to non-responders.
      Stepwise logistic regression analysis revealed no prognosticators of RDN response
      (p=NS for all). At 24 months there were no new serious device or procedure
      related adverse events. CONCLUSIONS: The EnligHTN I study shows that the multi
      electrode ablation system provides a safe method of RDN in dRHT accompanied by a
      clinically relevant and sustained BP reduction.

PMID- 26301678
TI  - MicroRNA-facilitated gene delivery: A potential therapeutic approach for vascular
      restenosis without influencing endothelial function.

PMID- 26301679
TI  - The diagnostic value of transthoracic echocardiography for eosinophilic
      myocarditis: A single center experience from China.
AB  - The aim of this study is to explore the value of transthoracic echocardiography
      in the diagnosis of eosinophilic myocarditis. The echocardiographic
      characteristics of nine patients with eosinophilic myocarditis in our hospital
      between January 2004 and January 2012 were retrospectively reviewed. In our
      study, four of the nine patients were diagnosed to have small pericardial
      effusion. The obliteration of the apical cavity was observed in five of the nine
      patients. There were six patients with both mitral and tricuspid regurgitation,
      one patient with only mitral regurgitation, and one patient with only tricuspid
      regurgitation. Transthoracic echocardiography showed that the diameters of the
      left and right atria were both increased in eight of the nine patients. The
      diameter of the left ventricle was increased in five patients, and the right
      ventricular diameter was increased in four patients. The left ventricular
      ejection fraction was decreased in two of the nine patients. Five of the nine
      patients had pulmonary hypertension, and one patient had severe pulmonary
      hypertension. Transthoracic echocardiography is the primary method for the
      diagnosis of eosinophilic myocarditis and is also useful in follow-up of the
      disease. 

PMID- 26301680
TI  - A Stochastic Model for CD4+ T Cell Proliferation and Dissemination Network in
      Primary Immune Response.
AB  - The study of the initial phase of the adaptive immune response after first
      antigen encounter provides essential information on the magnitude and quality of
      the immune response. This phase is characterized by proliferation and
      dissemination of T cells in the lymphoid organs. Modeling and identifying the key
      features of this phenomenon may provide a useful tool for the analysis and
      prediction of the effects of immunization. This knowledge can be effectively
      exploited in vaccinology, where it is of interest to evaluate and compare the
      responses to different vaccine formulations. The objective of this paper is to
      construct a stochastic model based on branching process theory, for the
      dissemination network of antigen-specific CD4+ T cells. The devised model is
      validated on in vivo animal experimental data. The model presented has been
      applied to the vaccine immunization context making references to simple
      proliferation laws that take into account division, death and quiescence, but it
      can also be applied to any context where it is of interest to study the dynamic
      evolution of a population. 

PMID- 26301681
TI  - Absorption Spectroscopy, a Tool for Probing Local Structures and the Onset of
      Large-Amplitude Motions in Small KAr(n) Clusters at Increasing Temperatures.
AB  - Photoabsorption spectra of KArn (n = 1-10) are simulated at temperatures ranging
      between 5 and 25 K. The calculations associate a Monte Carlo (MC) method to
      sample cluster geometries at temperature T, with a one-electron ab initio model
      to calculate the ground-state and excited-state energies of the cluster. The
      latter model replaces the K(+) core electrons and all the electrons of the Ar
      atoms by appropriate pseudopotentials, complemented by core polarization
      potentials. It also provides the necessary oscillator strengths to simulate the
      spectra. Global optimization by basin-hopping is used in combination with MC
      simulation at low temperature (5 K) to identify the most stable isomer and
      remarkable isomers of ground-state KArn clusters, which are stable with respect
      to deformations of the order of those expected with Zero Point Energy motions.
      The absorption spectra calculated for each of these isomers at 5 K suggest that
      absorption spectroscopy can probe sensitively the local environment of K atom:
      surface location of K with respect to a close-packed Ar moiety, number of Ar atom
      in close vicinity, and local symmetry about K. Simulation at increasing
      temperatures, up to the evaporation limit of K out of the cluster, shows the
      onset of large amplitude motions above 20 K, when the K atom experiences a
      variety of local environments. 

PMID- 26301682
TI  - Patent vitellointestinal duct as paraumblical abcess: A rare presentation.
AB  - INTRODUCTION: Umbilical and paraumblical abscess can occur in children with
      presenting complaint of discharge from umbilical region. However, patent vitello
      intestinal duct presenting as paraumblical abscess is rare phenomenon.
      PRESENTATION OF CASE: One year old male child presented with complain of
      discharge from umbilical region since birth. Incision & drainage done twice
      thinking it to be paraumblical abscess. DISCUSSION: Vitellointestinal duct as
      abscess is rare presentation but it should be considered as a differential
      diagnosis of discharging umbilicus as management of abscess and patent duct are
      different. CONCLUSION: Patent vitellointestinal duct can present as paraumbilical
      abscess, and it should be kept in differential diagnosis specifically in
      children.

PMID- 26301683
TI  - Resection of giant pseudoangiomatous stromal hyperplasia: Expectant observation
      and avoidance of complex breast surgery.
AB  - INTRODUCTION: Pseudoangiomatous stromal hyperplasia (PASH) is a benign tumor of
      the breast that can achieve large, or even giant, dimensions. Resection of giant
      tumors can pose cosmetic challenges. CASE PRESENTATION: We report the prospective
      cosmetic outcome of a 31-year old female with a 21-cm PASH tumor of the right
      breast using simple excision through an inframammary approach. The patient was
      followed for 6 months before final cosmesis was established. Breast cosmesis was
      considered very good by both patient and physician. Mild external rotation of the
      nipple and mild contour changes involving the lateral aspect of the breast
      persisted at 6 months. DISCUSSION: Avoidance of more complex alternatives such as
      reduction mammoplasty and/or mastopexy was achieved by allowing the skin envelope
      to undergo natural involution over a period of six months. CONCLUSION:
      Inframammary simple excision of a giant PASH tumor is appropriate in select
      patients.

PMID- 26301684
TI  - From Graphene Nanoribbons on Cu(111) to Nanographene on Cu(110): Critical Role of
      Substrate Structure in the Bottom-Up Fabrication Strategy.
AB  - Bottom-up strategies can be effectively implemented for the fabrication of
      atomically precise graphene nanoribbons. Recently, using 10,10'-dibromo-9,9'
      bianthracene (DBBA) as a molecular precursor to grow armchair nanoribbons on
      Au(111) and Cu(111), we have shown that substrate activity considerably affects
      the dynamics of ribbon formation, nonetheless without significant modifications
      in the growth mechanism. In this paper we compare the on-surface reaction
      pathways for DBBA molecules on Cu(111) and Cu(110). Evolution of both systems has
      been studied via a combination of core-level X-ray spectroscopies, scanning
      tunneling microscopy, and theoretical calculations. Experimental and theoretical
      results reveal a significant increase in reactivity for the open and anisotropic
      Cu(110) surface in comparison with the close-packed Cu(111). This increased
      reactivity results in a predominance of the molecular-substrate interaction over
      the intermolecular one, which has a critical impact on the transformations of
      DBBA on Cu(110). Unlike DBBA on Cu(111), the Ullmann coupling cannot be realized
      for DBBA/Cu(110) and the growth of nanoribbons via this mechanism is blocked.
      Instead, annealing of DBBA on Cu(110) at 250  degrees C results in the formation
      of a new structure: quasi-zero-dimensional flat nanographenes. Each nanographene
      unit has dehydrogenated zigzag edges bonded to the underlying Cu rows and
      oriented with the hydrogen-terminated armchair edge parallel to the [1-10]
      direction. Strong bonding of nanographene to the substrate manifests itself in a
      high adsorption energy of -12.7 eV and significant charge transfer of 3.46e from
      the copper surface. Nanographene units coordinated with bromine adatoms are able
      to arrange in highly regular arrays potentially suitable for nanotemplating. 

PMID- 26301685
TI  - The importance of pH and sand substrate in the revegetation of saline non
      waterlogged peat fields.
AB  - A partially peat-extracted coastal bog contaminated by seawater was barren and
      required revegetation as a wetland. Peat fields were rectangular in shape,
      cambered in cross-section profile, and separated by drainage ditches. Common to
      all peat fields were symmetrical patterns in micro-topography with slopes between
      differences in elevation. Saline non-waterlogged slopes of ~5% occurred as a
      symmetrical pair on each side of the crest of the cambered profile, at one end of
      each peat field. Three rows were laid across this slope (Top, Middle, and Bottom
      rows) and transplanted with naturally-growing plant species with their sand
      substrate, in three experiments, and grown for a year. In the Spartina pectinata
      experiment, bare root stem sections were also planted. Another experiment was
      conducted to determine changes in the characteristics of a volume of sand when
      incubated in saline peat fields. We found the salinity of peat increased with
      moisture downslope, and pH decreased with increase in salinity. S. pectinata grew
      best when planted with its sand substrate compared with bare root stem section,
      and when planted in Bottom rows. Juncus balticus had excellent growth in all
      rows. Unexpectedly, Festuca rubra that was inconspicuous beneath the J. balticus
      canopy in the natural donor site grew densely within the J. balticus sods.
      Agrostis stolonifera grew well but seemed to show intolerance to the surrounding
      acidic peat by curling up its stolons. The pH of the incubated sand volume was
      much higher than the surrounding peat. These studies suggest that recognition of
      plant niches and pH manipulation are important in the revegetation of disturbed
      Sphagnum peatlands that are found abundantly in the northern hemisphere. Results
      are also relevant to the reclamation of other disturbed lands. 

PMID- 26301686
TI  - Medical waste management - A review.
AB  - This paper examines medical waste management, including the common sources,
      governing legislation and handling and disposal methods. Many developed nations
      have medical waste legislation, however there is generally little guidance as to
      which objects can be defined as infectious. This lack of clarity has made sorting
      medical waste inefficient, thereby increasing the volume of waste treated for
      pathogens, which is commonly done by incineration. This review highlights that
      the unnecessary classification of waste as infectious results in higher disposal
      costs and an increase in undesirable environmental impacts. The review concludes
      that better education of healthcare workers and standardized sorting of medical
      waste streams are key avenues for efficient waste management at healthcare
      facilities, and that further research is required given the trend in increased
      medical waste production with increasing global GDP. 

PMID- 26301687
TI  - Enhancing seedling production of native species to restore gypsum habitats.
AB  - Gypsum habitats are widespread globally and are important for biological
      conservation. Nevertheless, they are often affected by human disturbances and
      thus require restoration. Sowing and planting have shown positive results, but
      these actions are usually limited by the lack of native plant material in
      commercial nurseries, and very little information is available on the propagation
      of these species. We address this issue from the hypothesis that gypsum added to
      a standard nursery growing medium (peat) can improve seedling performance of
      gypsum species and, therefore, optimise the seedling production for outplanting
      purposes. We test the effect of gypsum on emergence, survival, and growth of nine
      native plant species, including gypsophiles (exclusive to gypsum) and gypsovags
      (non-exclusive to gypsum). We used four treatments according to the proportions,
      in weight, of gypsum:standard peat (G:S), i.e. high-g (50G:50S), medium-g
      (25G:75S), low-g (10G:90S), and standard-p (0G:100S). Our results showed that the
      gypsum treatments especially benefited the emergence stage, gypsophiles as group,
      and Ononis tridentata as a taxon. In particular, the gypsum treatments enhanced
      emergence of seven species, survival of three species, and growth of two
      gypsophiles, while the use of the standard peat favoured only the emergence or
      growth of three gypsovags. Improving emergence and survival at the nursery can
      provide a reduction of costs associated with seed harvesting, watering, and
      space, while enlarging seedlings can favour the establishment of individuals
      after outplanting. Thus, we suggest adding gypsum to standard peat for
      propagating seedlings in species from gypsum habitats, thereby potentially
      cutting the costs of restoring such habitats. Our assessment enables us to
      provide particular advice by species. In general, we recommend using between 25
      and 50% of gypsum to propagate gypsophiles, and between 0 and 10% for gypsovags.
      The results can benefit not only the production of widely distributed species
      commonly affected by gypsum quarrying, but also of narrow and threatened endemic
      species that require particularly efficient use of their seeds. In addition, our
      study highlights the importance of using appropriate growing media to propagate
      plants characteristic of special substrates for restoration purposes. 

PMID- 26301689
TI  - RAS-MAPK dependence underlies a rational polytherapy strategy in EML4-ALK
      positive lung cancer.
AB  - One strategy for combating cancer-drug resistance is to deploy rational
      polytherapy up front that suppresses the survival and emergence of resistant
      tumor cells. Here we demonstrate in models of lung adenocarcinoma harboring the
      oncogenic fusion of ALK and EML4 that the GTPase RAS-mitogen-activated protein
      kinase (MAPK) pathway, but not other known ALK effectors, is required for tumor
      cell survival. EML4-ALK activated RAS-MAPK signaling by engaging all three major
      RAS isoforms through the HELP domain of EML4. Reactivation of the MAPK pathway
      via either a gain in the number of copies of the gene encoding wild-type K-RAS
      (KRAS(WT)) or decreased expression of the MAPK phosphatase DUSP6 promoted
      resistance to ALK inhibitors in vitro, and each was associated with resistance to
      ALK inhibitors in individuals with EML4-ALK-positive lung adenocarcinoma. Upfront
      inhibition of both ALK and the kinase MEK enhanced both the magnitude and
      duration of the initial response in preclinical models of EML4-ALK lung
      adenocarcinoma. Our findings identify RAS-MAPK dependence as a hallmark of EML4
      ALK lung adenocarcinoma and provide a rationale for the upfront inhibition of
      both ALK and MEK to forestall resistance and improve patient outcomes. 

PMID- 26301692
TI  - Influence of organic amendment on fate of acetaminophen and sulfamethoxazole in
      soil.
AB  - Land application of biosolids or compost constitutes an important route of soil
      contamination by emerging contaminants such as acetaminophen and
      sulfamethoxazole. Using (14)C labeling, we evaluated the influence of biosolids
      and compost on individual fate processes of acetaminophen and sulfamethoxazole in
      soil. The amendment of biosolids or compost consistently inhibited the
      mineralization of both compounds but simultaneously enhanced the dissipation of
      their extractable residues or parent form. Immediately after treatment, the
      majority of (14)C-residue became non-extractable, reaching 80.3-92.3% of the
      applied amount at the end of 84-d incubation. Addition of biosolids or compost
      appreciably accelerated the formation of bound residue, likely due to the fact
      that the organic material provided additional sites for binding interactions or
      introduced exogenous microorganisms facilitating chemical transformations. This
      effect of biosolids or compost should be considered in risk assessment of these
      and other emerging contaminants. 

PMID- 26301690
TI  - Nogo-B regulates endothelial sphingolipid homeostasis to control vascular
      function and blood pressure.
AB  - Endothelial dysfunction is a critical factor in many cardiovascular diseases,
      including hypertension. Although lipid signaling has been implicated in
      endothelial dysfunction and cardiovascular disease, specific molecular mechanisms
      are poorly understood. Here we report that Nogo-B, a membrane protein of the
      endoplasmic reticulum, regulates endothelial sphingolipid biosynthesis with
      direct effects on vascular function and blood pressure. Nogo-B inhibits serine
      palmitoyltransferase, the rate-limiting enzyme of the de novo sphingolipid
      biosynthetic pathway, thereby controlling production of endothelial sphingosine 1
      phosphate and autocrine, G protein-coupled receptor-dependent signaling by this
      metabolite. Mice lacking Nogo-B either systemically or specifically in
      endothelial cells are hypotensive, resistant to angiotensin II-induced
      hypertension and have preserved endothelial function and nitric oxide release. In
      mice that lack Nogo-B, pharmacological inhibition of serine palmitoyltransferase
      with myriocin reinstates endothelial dysfunction and angiotensin II-induced
      hypertension. Our study identifies Nogo-B as a key inhibitor of local
      sphingolipid synthesis and shows that autocrine sphingolipid signaling within the
      endothelium is critical for vascular function and blood pressure homeostasis. 

PMID- 26301691
TI  - Hemagglutinin-stem nanoparticles generate heterosubtypic influenza protection.
AB  - The antibody response to influenza is primarily focused on the head region of the
      hemagglutinin (HA) glycoprotein, which in turn undergoes antigenic drift, thus
      necessitating annual updates of influenza vaccines. In contrast, the
      immunogenically subdominant stem region of HA is highly conserved and recognized
      by antibodies capable of binding multiple HA subtypes. Here we report the
      structure-based development of an H1 HA stem-only immunogen that confers
      heterosubtypic protection in mice and ferrets. Six iterative cycles of structure
      based design (Gen1-Gen6) yielded successive H1 HA stabilized-stem (HA-SS)
      immunogens that lack the immunodominant head domain. Antigenic characterization,
      determination of two HA-SS crystal structures in complex with stem-specific
      monoclonal antibodies and cryo-electron microscopy analysis of HA-SS on ferritin
      nanoparticles (H1-SS-np) confirmed the preservation of key structural elements.
      Vaccination of mice and ferrets with H1-SS-np elicited broadly cross-reactive
      antibodies that completely protected mice and partially protected ferrets against
      lethal heterosubtypic H5N1 influenza virus challenge despite the absence of
      detectable H5N1 neutralizing activity in vitro. Passive transfer of
      immunoglobulin from H1-SS-np-immunized mice to naive mice conferred protection
      against H5N1 challenge, indicating that vaccine-elicited HA stem-specific
      antibodies can protect against diverse group 1 influenza strains. 

PMID- 26301693
TI  - Antioxidative and immunological responses in the haemolymph of wolf spider
      Xerolycosa nemoralis (Lycosidae) exposed to starvation and dimethoate.
AB  - The aim of this study was to assess the intensity of enzymatic antioxidative
      parameters [catalase (CAT), glutathione peroxidase (GSTPx), glutathione reductase
      (GR), total antioxidant capacity (TAC)] and percentage of high granularity cells
      as well as low to medium granularity cells in haemolymph of wolf spiders
      Xerolycosa nemoralis exposed to starvation and dimethoate under laboratory
      conditions. Only in starved males, haemolymph included a lower percentage of high
      granularity cells, accompanied by high activity of CAT and GSTPx, than in the
      control. Exposure of males to dimethoate increased CAT activity, after single
      application, and significantly enhanced GR activity, after five-time application.
      In females, five-time contact with dimethoate elevated the percentage of high
      granularity cells. As in comparison to females, male X. nemoralis were more
      sensitive to the applied stressing factors, it may be concluded that in natural
      conditions both food deficiency and chemical stress may diminish the immune
      response of their organisms. 

PMID- 26301688
TI  - Meta-analysis of shared genetic architecture across ten pediatric autoimmune
      diseases.
AB  - Genome-wide association studies (GWASs) have identified hundreds of
      susceptibility genes, including shared associations across clinically distinct
      autoimmune diseases. We performed an inverse chi(2) meta-analysis across ten
      pediatric-age-of-onset autoimmune diseases (pAIDs) in a case-control study
      including more than 6,035 cases and 10,718 shared population-based controls. We
      identified 27 genome-wide significant loci associated with one or more pAIDs,
      mapping to in silico-replicated autoimmune-associated genes (including IL2RA) and
      new candidate loci with established immunoregulatory functions such as ADGRL2,
      TENM3, ANKRD30A, ADCY7 and CD40LG. The pAID-associated single-nucleotide
      polymorphisms (SNPs) were functionally enriched for deoxyribonuclease (DNase)
      hypersensitivity sites, expression quantitative trait loci (eQTLs), microRNA
      (miRNA)-binding sites and coding variants. We also identified biologically
      correlated, pAID-associated candidate gene sets on the basis of immune cell
      expression profiling and found evidence of genetic sharing. Network and protein
      interaction analyses demonstrated converging roles for the signaling pathways of
      type 1, 2 and 17 helper T cells (TH1, TH2 and TH17), JAK-STAT, interferon and
      interleukin in multiple autoimmune diseases. 

PMID- 26301694
TI  - Accumulation and phytotoxicity of perfluorooctanoic acid in the model plant
      species Arabidopsis thaliana.
AB  - Perfluorooctanoic acid (PFOA) is widely used in the manufacture of many
      industrial and household products. To assess the potential environmental risk of
      PFOA, its accumulation, translocation and phytotoxic effects were investigated
      using the model plant species Arabidopsis thaliana. Exposure to 18 MUM PFOA-F in
      agar plates did not affect plant growth, but 181-1811 MUM PFOA-F inhibited root
      and shoot growth. PFOA was more phytotoxic on shoot growth than NaF at the
      equivalent F concentration, with the latter having 3.9-7.6 times higher EC50 for
      shoot biomass than PFOA. PFOA was efficiently translocated from roots to shoots,
      where it existed as intact PFOA molecules without transformation evidenced by the
      (19)F NMR spectra. PFOA caused a significant increase in the concentration of
      H2O2 and malondialdehyde (MDA) in shoots, indicating that oxidative stress is a
      likely cause of PFOA phytotoxicity. 

PMID- 26301696
TI  - High-Performance Sensors Based on Resistance Fluctuations of Single-Layer
      Graphene Transistors.
AB  - One of the most interesting predicted applications of graphene-monolayer-based
      devices is as high-quality sensors. In this article, we show, through systematic
      experiments, a chemical vapor sensor based on the measurement of low-frequency
      resistance fluctuations of single-layer-graphene field-effect-transistor devices.
      The sensor has extremely high sensitivity, very high specificity, high fidelity,
      and fast response times. The performance of the device using this scheme of
      measurement (which uses resistance fluctuations as the detection parameter) is
      more than 2 orders of magnitude better than a detection scheme in which changes
      in the average value of the resistance is monitored. We propose a number-density
      fluctuation-based model to explain the superior characteristics of a noise
      measurement-based detection scheme presented in this article. 

PMID- 26301695
TI  - Environmentally realistic concentrations of the antibiotic Trimethoprim affect
      haemocyte parameters but not antioxidant enzyme activities in the clam Ruditapes
      philippinarum.
AB  - Several biomarkers were measured to evaluate the effects of Trimethoprim (TMP;
      300, 600 and 900 ng/L) in the clam Ruditapes philippinarum after exposure for 1,
      3 and 7 days. The actual TMP concentrations were also measured in the
      experimental tanks. The total haemocyte count significantly increased in 7 day
      exposed clams, whereas alterations in haemocyte volume were observed after 1 and
      3 days of exposure. Haemocyte proliferation was increased significantly in
      animals exposed for 1 and 7 days, whereas haemocyte lysate lysozyme activity
      decreased significantly after 1 and 3 days. In addition, TMP significantly
      increased haemolymph lactate dehydrogenase activity after 3 and 7 days. Regarding
      antioxidant enzymes, only a significant time-dependent effect on CAT activity was
      recorded. This study demonstrated that environmentally realistic concentrations
      of TMP affect haemocyte parameters in clams, suggesting that haemocytes are a
      useful cellular model for the assessment of the impact of TMP on bivalves. 

PMID- 26301698
TI  - Self-directedness and the susceptibility to distraction by saliency.
AB  - People with low Self-directedness (SD) tend to explain their behaviour as being
      significantly influenced by events in the external environment. One important
      dimension of external cues is their level of salience: highly salient external
      stimuli are more likely to capture attention, even when such stimuli are not
      relevant to goals. We examined whether adults reporting low SD would exhibit
      greater susceptibility to distraction by highly salient external stimuli. Fifty
      four (42 males) subjects completed the Attention Modulation by Salience Task
      (AMST) measuring reaction times to early- or late-onset auditory stimuli in the
      presence of high- or low-salience visual distractors. SD was assessed via self
      report, and analyses tested the relationship between SD and performance on the
      AMST. Results showed a slowed early response to auditory cues during high
      salience compared to low salience. Indeed, individuals reporting low SD showed
      stronger salience interference, suggesting that external causality attribution is
      accompanied by a subconscious perceptual deficit.

PMID- 26301697
TI  - Immunodiagnosis of platelet activation in immune thrombocytopenia through scFv
      antibodies cognate to activated IIb3 integrins.
AB  - Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by
      low platelet count and presence of IgG autoantibodies to platelet surface
      glycoproteins, such as alpha IIbbeta3 and GPIb/IX. Our previous work has shown
      that platelets in ITP patients exist in an activated state. Two different marker
      based approaches are used to study the course of platelet activation: (1) binding
      of PAC-1 antibody, signifying a change in alphaIIbbeta3 conformation, and (2)
      expression of P-selectin, signifying alpha granule content release from
      platelets. Here, we describe the development of a new scFv antibody (R38) that,
      compared with PAC-1, appears to better distinguish between platelets of ITP
      patients and healthy controls. Notably, R38 was generated using commercially
      sourced resting-state integrin that was coated on a microtiter plate. Its ability
      to distinguish between ITP patients and healthy controls thus suggests that
      inadvertent integrin activation caused by coating involves a conformational
      change and exposure of a cryptic epitope. This report also describes for the
      first time the potential use of an scFv antibody in the immunodiagnosis of
      platelet activation in ITP patients. 

PMID- 26301699
TI  - The Quest for Simplicity: Remarks on the Free-Approach Models.
AB  - Nuclear magnetic relaxation provides a powerful method giving insight into
      molecular motions at atomic resolution on a broad time scale. Dynamics of
      biological macromolecules has been widely exploited by measuring (15)N and (13)C
      relaxation data. Interpretation of these data relies almost exclusively on the
      use of the model-free approach (MFA) and its extended version (EMFA) which
      requires no particular physical model of motion and a small number of parameters.
      It is shown that EMFA is often unable to cope with three different time scales
      and fails to describe slow internal motions properly. In contrast to EMFA,
      genuine MFA with two time scales can reproduce internal motions slower than the
      overall tumbling. It is also shown that MFA and simplified EMFA are equivalent
      with respect to the values of the N-H bond length and chemical shift anisotropy.
      Therefore, the vast majority of (15)N relaxation data for proteins can be
      satisfactorily interpreted solely with MFA. 

PMID- 26301700
TI  - Hyaluronic acid-conjugated apoferritin nanocages for lung cancer targeted drug
      delivery.
AB  - In this paper, we proposed a naturally derived protein cage based pH-responsive
      delivery system for intracellular prodrug controlled release. The drug delivery
      system is based on apoferritin as delivery vehicles to encapsulate the anticancer
      drug daunomycin (DN) and alleviate the side effect. The hydrophobic drug DN was
      encapsulated into the interior of apoferritin by the hydrophobic channels of the
      cage with swelling at slight acidic pH and electrostatic adsorption. The
      negatively charged poly-l-aspartic acid (PLAA) was further introduced into the
      apoferritin to absorb the positively charged DN. The mixture of PLAA and DN
      easily flew into the apoferritin cage and was stably stored in the physiological
      fluids. PLAA protected the leakage of DN and encapsulated a sufficient amount of
      drug molecules in the cage. To specifically target the tumor cells, the surface
      of apoferritin was modified with hyaluronic acid (HA) which can easily bind to
      the HA-receptor CD44. Here, human embryonic lung MRC-5 cells and lung cancer A549
      cells were used to observe the specific binding of HA and morphological changes
      in vitro and examine the antitumor activity. This unique protein based drug
      delivery platform using the apoferritin cage shows great potential in the
      therapeutic administration of the anti-cancer agents. 

PMID- 26301701
TI  - Efficacy and safety of adjunctive brexpiprazole 2 mg in major depressive
      disorder: a phase 3, randomized, placebo-controlled study in patients with
      inadequate response to antidepressants.
AB  - OBJECTIVE: To assess the efficacy, tolerability, and safety of brexpiprazole as
      adjunctive therapy to antidepressant treatments (ADTs) in adults with major
      depressive disorder (as defined by DSM-IV-TR criteria) and inadequate response to
      ADTs. METHOD: Patients with historical inadequate response to 1-3 ADTs were
      enrolled. All patients entered a prospective 8-week phase on physician
      determined, open-label ADT. Those with inadequate response were randomized to ADT
      + brexpiprazole 2 mg/d or ADT + placebo for 6 weeks. The study was conducted
      between July 2011 and May 2013. The primary efficacy end point was change from
      baseline to week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) total
      score. The key secondary end point was change from baseline to week 6 in Sheehan
      Disability Scale (SDS) mean score. The efficacy population comprised all patients
      who had >= 1 dose of study drug in the double-blind phase and both baseline and
      >= 1 postrandomization MADRS scores. The efficacy population per final protocol
      included patients from the efficacy population who met amended randomization
      criteria of inadequate response throughout prospective treatment. RESULTS:
      Brexpiprazole (n = 175) reduced mean MADRS total score versus placebo (n = 178)
      at week 6 in the efficacy population per final protocol (-8.36 vs -5.15, P =
      .0002). Brexpiprazole improved SDS mean score versus placebo (-1.35 vs -0.89, P =
      .0349). The most common treatment-related adverse events were weight gain
      (brexpiprazole, 8.0%; placebo, 3.1%) and akathisia (7.4% vs 1.0%). CONCLUSIONS:
      Adjunctive brexpiprazole therapy demonstrated efficacy and was well tolerated in
      patients with major depressive disorder and inadequate response to ADTs. TRIAL
      REGISTRATION: ClinicalTrials.gov identifier: NCT01360645.

PMID- 26301702
TI  - Achieving Core Indicators for HIV Clinical Care Among New Patients at an Urban
      HIV Clinic.
AB  - Following the release of the 2010 National HIV/AIDS Strategy for the United
      States, the Institute of Medicine (IOM) issued core clinical indicators for
      measuring health outcomes in HIV-positive persons. As early retention in HIV
      primary care is associated with improved long-term health outcomes, we employed
      IOM indicators as a guide to examine a cohort of persons initiating HIV
      outpatient medical care at a university-affiliated HIV clinic in the Southern
      United States (January 2007-July 2012). Using indicators for visit attendance,
      CD4 and viral load laboratory testing frequency, and antiretroviral therapy
      initiation, we evaluated factors associated with achieving IOM core indicators
      among care- and treatment-naive patients during the first year of HIV care. Of
      448 patients (mean age = 35 years, 35.7% white, 79.0% male, 58.4% education
      beyond high school, 35.9% monthly income > $1,000 US, 47.3% uninsured), 84.6%
      achieved at least four of five IOM indicators. In multivariable analyses, persons
      with monthly income > $1,000 (ORadj. = 3.71; 95% CI: 1.68-8.19; p = 0.001) and
      depressive symptoms (ORadj. = 2.13; 95% CI: 1.02-4.45; p = 0.04) were
      significantly more likely to achieve at least four of the five core indicators,
      while patients with anxiety symptoms were significantly less likely to achieve
      these indicators (ORadj. = 0.50; 95% CI: 0.26-0.97; p = 0.04). Age, sex, race,
      education, insurance status, transportation barriers, alcohol use, and HIV status
      disclosure to family were not associated with achieving core indicators.
      Evaluating and addressing financial barriers and anxiety symptoms during the
      first year of HIV outpatient care may improve individual health outcomes and
      subsequent achievement of the National HIV/AIDS Strategy. 

PMID- 26301704
TI  - Predicting Arsenic Relative Bioavailability Using Multiple in Vitro Assays:
      Validation of in Vivo-in Vitro Correlations.
AB  - In this study, previously established arsenic (As) in vivo-in vitro correlations
      (IVIVC) were assessed for their validity using an independent data set comprising
      As relative bioavailability (RBA) and bioaccessibility values for 13 herbicide-
      and mine-impacted soils. The validation process established the correlation
      between As RBA (swine model) and bioaccessibility (five in vitro assays),
      determined whether correlations differed significantly from previous
      relationships and assessed model bias and error. The capacity of in vitro assays
      to predict As RBA was demonstrated by the strength of IVIVC; goodness of fit
      ranged from 0.53 (DIN-I) to 0.74 (UBM-I). When compared to previous IVIVC (Juhasz
      et al. Environ. Sci. Technol. 2009 , 43 , 9487 ; Juhasz et al. J. Hazard. Mater.
      2011 , 197 , 161 ), there was no significant difference (P < 0.01) in the slope
      and y-intercept for IVG-G, UBM-G, and UBM-I indicating the consistency of these
      assays for predicting As RBA. However, variability in model bias and prediction
      error was observed with significantly lower (P < 0.01) error determined for IVG-G
      suggesting that As RBA predictions using IVG-G may be more robust compared to UBM
      G and UBM-I. In contrast, differences in the slope and/or y-intercept were
      observed for SBRC-I, IVG-I, PBET-G, PBET-I, DIN-G, and DIN-I suggesting that
      these methodologies may not be suitable for predicting As RBA. 

PMID- 26301703
TI  - Fertility Decision-Making Among Kenyan HIV-Serodiscordant Couples Who Recently
      Conceived: Implications for Safer Conception Planning.
AB  - HIV-serodiscordant couples often choose to attempt pregnancy despite their HIV
      transmission risk. Optimizing delivery of HIV risk reduction strategies during
      peri-conception periods (i.e., safer conception) requires understanding how HIV
      serodiscordant couples approach fertility decisions. We conducted 36 in-depth
      individual interviews with male and female partners of Kenyan heterosexual HIV
      serodiscordant couples who recently conceived. Transcripts were analyzed by
      gender and HIV serostatus using open coding. Matrices were used to identify
      patterns and emerging themes. Most participants expressed acceptance of being in
      an HIV-serodiscordant couple and affirmed their resilience to live with
      serodiscordance and achieve their fertility goals. Overall, while the goal for
      childbearing was unchanged, conception became an urgent desire so that both
      partners could experience childrearing together while the HIV-infected partner
      was still healthy. Children also add value to the relationship, and multiple
      children were a commonly expressed desire. Couples' desires dominated those of
      individual partners in fertility decision-making, but male preferences were more
      influential when the individual desires differed. Values and preferences of the
      couple as a unit may mediate fertility decision-making in HIV-discordant couples.
      Thus, it is important that safer conception programs include both partners when
      appropriate and consider the relationship context during risk reduction
      counseling and when recommending risk reduction interventions. 

PMID- 26301705
TI  - The Perseverative Thinking Questionnaire in Patients with Persecutory Delusions.
AB  - BACKGROUND: Ruminative negative thinking has typically been considered as a
      factor maintaining common emotional disorders and has recently been shown to
      maintain persecutory delusions in psychosis. The Perseverative Thinking
      Questionnaire (PTQ) (Ehring et al., 2011) is a transdiagnostic measure of
      ruminative negative thinking that shows promise as a "content-free" measure of
      ruminative negative thinking. AIMS: The PTQ has not previously been studied in a
      psychosis patient group. In this study we report for the first time on the
      psychometric properties of Ehring et al.'s PTQ in such a group. METHOD: The PTQ
      was completed by 142 patients with current persecutory delusions and 273 non
      clinical participants. Participants also completed measures of worry and
      paranoia. A confirmatory factor analysis was performed on the clinical group's
      PTQ responses to assess the factor structure of the measure. Differences between
      groups were used to assess criterion reliability. RESULTS: A three lower-order
      factor structure of the PTQ (core characteristics of ruminative negative
      thinking, perceived unproductiveness, and capturing mental capacity) was
      replicated in the clinical sample. Patients with persecutory delusions were shown
      to experience significantly higher levels of ruminative negative thinking on the
      PTQ than the general population sample. The PTQ demonstrated high internal
      reliability. CONCLUSIONS: This study did not include test-retest data, and did
      not compare the PTQ against a measure of depressive rumination but, nevertheless,
      lends support for the validity of the PTQ as a measure of negative ruminative
      thinking in patients with psychosis.

PMID- 26301707
TI  - Crucial Role for Outdoor Chemistry in Ultrafine Particle Formation in Modern
      Office Buildings.
AB  - In the developed world, we spend most of our time indoors, where we receive the
      majority of our exposure to air pollution. This paper reports model simulations
      of PM2.5 and ozone concentrations in identical landscape offices in three
      European cities: Athens, Helsinki, and Milan. We compare concentrations during an
      intense heatwave in August 2003 with a meteorologically more typical August in
      2009. During the heatwave, average indoor ozone concentrations during office
      hours were 44, 19, and 41 ppb in Athens, Helsinki, and Milan respectively,
      enhanced by 7, 4, and 17 ppb respectively relative to 2009. Total predicted PM2.5
      concentrations were 13.5, 3.6, and 17.2 MUg m(-3) in Athens, Helsinki, and Milan
      respectively, enhanced by 0.5, 0.4, and 6.7 MUg m(-3) respectively relative to
      2009: the three cities were affected to differing extents by the heatwave. A
      significant portion of the indoor PM2.5 derived from gas-phase chemistry
      outdoors, producing 2.5, 0.8, and 4.8 MUg m(-3) of the total concentrations in
      Athens, Helsinki, and Milan, respectively. Despite filtering office inlet
      supplies to remove outdoor particles, gas-phase precursors for particles can
      still enter offices, where conditions are ripe for new particles to form,
      particularly where biogenic emissions are important outdoors. This result has
      important implications for indoor air quality, particularly given the current
      trend for green walls on buildings, which will provide a potential source of
      biogenic emissions near to air inlet systems. 

PMID- 26301706
TI  - Active Video Game Exercise Training Improves the Clinical Control of Asthma in
      Children: Randomized Controlled Trial.
AB  - OBJECTIVE: The aim of the present study was to determine whether aerobic exercise
      involving an active video game system improved asthma control, airway
      inflammation and exercise capacity in children with moderate to severe asthma.
      DESIGN: A randomized, controlled, single-blinded clinical trial was carried out.
      Thirty-six children with moderate to severe asthma were randomly allocated to
      either a video game group (VGG; N = 20) or a treadmill group (TG; n = 16). Both
      groups completed an eight-week supervised program with two weekly 40-minute
      sessions. Pre-training and post-training evaluations involved the Asthma Control
      Questionnaire, exhaled nitric oxide levels (FeNO), maximum exercise testing
      (Bruce protocol) and lung function. RESULTS: No differences between the VGG and
      TG were found at the baseline. Improvements occurred in both groups with regard
      to asthma control and exercise capacity. Moreover, a significant reduction in
      FeNO was found in the VGG (p < 0.05). Although the mean energy expenditure at
      rest and during exercise training was similar for both groups, the maximum energy
      expenditure was higher in the VGG. CONCLUSION: The present findings strongly
      suggest that aerobic training promoted by an active video game had a positive
      impact on children with asthma in terms of clinical control, improvement in their
      exercise capacity and a reduction in pulmonary inflammation. TRIAL REGISTRATION:
      Clinicaltrials.gov NCT01438294.

PMID- 26301708
TI  - A multidimensional model of police legitimacy: A cross-cultural assessment.
AB  - This study used survey data from cross-sectional, university-based samples of
      young adults in different cultural settings (i.e., the United States and Ghana)
      to accomplish 2 main objectives: (1) to construct a 4-dimensional police
      legitimacy scale, and (2) to assess the relationship that police legitimacy and
      feelings of obligation to obey the police have with 2 outcome measures. The fit
      statistics for the second-order confirmatory factor models indicated that the 4
      dimensional police legitimacy model is reasonably consistent with the data in
      both samples. Results from the linear regression analyses showed that the police
      legitimacy scale is related to cooperation with the police, and that the observed
      association is attenuated when the obligation to obey scale is included in the
      model specification in both the United States and Ghana data. A similar pattern
      emerged in the U.S. sample when estimating compliance with the law models.
      However, although police legitimacy was associated with compliance in the Ghana
      sample, this relationship along with the test statistic for the sense of
      obligation to obey estimate were both null in the fully saturated equation. The
      findings provide support for the Bottoms and Tankebe's (2012) argument that
      legitimacy is multidimensional, comprising police lawfulness, distributive
      fairness, procedural fairness, and effectiveness. However, the link between
      police legitimacy and social order appears to be culturally variable. 

PMID- 26301709
TI  - Putting bias into context: The role of familiarity in identification.
AB  - Previous demonstrations of context effects in the forensic comparison sciences
      have shown that the number of "match" responses a person makes can be swayed by
      case information. Less clear is whether these effects are a result of changes in
      accuracy (e.g., discrimination ability), a shift in response bias (e.g., tendency
      to say "match" or "no match") or a mix of the 2. We present a series of
      experiments where we use a signal detection framework to examine the effects of
      case information (separately) on forensic comparison accuracy and response bias.
      We also explore the role of familiarity as 1 potential mechanism for case
      information to sway accuracy. In Experiment 1, case information about crimes
      perceived to be more severe swayed people to say "match" more, but had little
      bearing on their ability to discriminate matching and nonmatching fingerprint
      pairs. In Experiment 2, case information did affect accuracy when it was familiar
      (i.e., if a previous similar case was associated with a "match" then people were
      more likely to also rate the current case as a "match," even though it was not).
      Even when we blinded people to all extrinsic case information in Experiment 3,
      accuracy was significantly affected by the familiarity of the fingerprints. These
      results demonstrate that contextual factors can have different (and independent)
      influences on accuracy and response bias and that even subtle information can
      affect accuracy if it is sufficiently similar to the case or trace at hand. 

PMID- 26301711
TI  - Lost proof of innocence: The impact of confessions on alibi witnesses.
AB  - The present study investigated how alibi witnesses react in the face of an
      innocent suspect's confession. Under the pretext of a problem-solving study, a
      participant and confederate completed a series of tasks in the same testing room.
      The confederate was subsequently accused of stealing money from an adjacent
      office during the study session. After initially corroborating the innocent
      confederate's alibi that she never left the testing room, only 45% of
      participants maintained their support of that alibi once informed that the
      confederate had confessed (vs. 95% when participants believed the confederate had
      denied involvement). Even fewer (20%) maintained their corroboration when the
      experimenter insinuated that their support of the alibi might imply their
      complicity. The presence of a confession also decreased participants' confidence
      in the accuracy of the alibi and their belief in the confederate's innocence.
      These findings suggest that a police-induced confession can strip an innocent
      confessor of a vital source of exculpatory evidence. This effect may well explain
      the often-puzzling absence of exculpatory evidence in many cases involving
      wrongful conviction. 

PMID- 26301710
TI  - Psychopathic traits as predictors of future criminality, intimate partner
      aggression, and substance use in young adult men.
AB  - This study examined the prospective relation between Youth Psychopathic Traits
      Inventory (YPI) scores and various negative outcomes in a community sample of
      young men. Official criminal records and self-reported outcomes, including
      criminality, physical and relational aggression against intimate partners, and
      excessive substance use, were obtained on average 5.4 years (records) and 3.5
      years (self-reports) after the YPI assessment. Results showed that psychopathic
      traits measured with the YPI (approximately at age 25) did not significantly
      contribute to the prediction of future official criminal charges and self
      reported crime, physical aggression against intimate partners, and excessive
      alcohol and marijuana use, after controlling for several covariates. However,
      results also showed that men with higher scores on the YPI were more likely to
      commit future acts of relational aggression against their partner, even after
      controlling for prior relational aggression. This novel finding needs
      replication, though, and-for now-does not jeopardize the overall conclusion that
      psychopathic traits as measured with the YPI hardly predict over and above prior
      criminality and aggression. Altogether, the findings of the present study and
      their consistency with past research suggest that one should rethink the role of
      psychopathy measures for risk assessment purposes, at least when these measures
      do not index prior criminality.

PMID- 26301712
TI  - Physical Activity Differentially Affects the Cecal Microbiota of Ovariectomized
      Female Rats Selectively Bred for High and Low Aerobic Capacity.
AB  - The gut microbiota is considered a relevant factor in obesity and associated
      metabolic diseases, for which postmenopausal women are particularly at risk.
      Increasing physical activity has been recognized as an efficacious approach to
      prevent or treat obesity, yet the impact of physical activity on the microbiota
      remains under-investigated. We examined the impacts of voluntary exercise on host
      metabolism and gut microbiota in ovariectomized (OVX) high capacity (HCR) and low
      capacity running (LCR) rats. HCR and LCR rats (age = 27 wk) were OVX and fed a
      high-fat diet (45% kcal fat) ad libitum and housed in cages equipped with
      (exercise, EX) or without (sedentary, SED) running wheels for 11 wk (n = 7
      8/group). We hypothesized that increased physical activity would hinder weight
      gain, increase metabolic health and shift the microbiota of LCR rats, resulting
      in populations more similar to that of HCR rats. Animals were compared for
      characteristic metabolic parameters including body composition, lipid profile and
      energy expenditure; whereas cecal digesta were collected for DNA extraction. 16S
      rRNA gene-based amplicon Illumina MiSeq sequencing was performed, followed by
      analysis using QIIME 1.8.0 to assess cecal microbiota. Voluntary exercise
      decreased body and fat mass, and normalized fasting NEFA concentrations of LCR
      rats, despite only running one-third the distance of HCR rats. Exercise, however,
      increased food intake, weight gain and fat mass of HCR rats. Exercise clustered
      the gut microbial community of LCR rats, which separated them from the other
      groups. Assessments of specific taxa revealed significant (p<0.05) line by
      exercise interactions including shifts in the abundances of Firmicutes,
      Proteobacteria, and Cyanobacteria. Relative abundance of Christensenellaceae
      family was higher (p = 0.026) in HCR than LCR rats, and positively correlated
      (p<0.05) with food intake, body weight and running distance. These findings
      demonstrate that exercise differentially impacts host metabolism and gut
      microbial communities of female HCR and LCR rats without ovarian function.

PMID- 26301714
TI  - Thermoresponsive Substrates Used for the Growth and Controlled Differentiation of
      Human Mesenchymal Stem Cells.
AB  - This communication outlines the advances made in the development of
      thermoresponsive substrates for human mesenchymal stem cell (hMSC) expansion and
      subsequent controlled specific and multilineage differentiation from a previous
      study performed by this group. Previously, the development of an inexpensive and
      technically accessible method for hMSC expansion and harvesting was reported,
      using the solvent casting deposition method and thermoresponsive poly(N
      isopropylacrylamide). Here, the logical continuation of this work is reported
      with the multipassage expansion of hMSCs with phenotypic maintenance followed by
      induced adipogenic, osteogenic, and chondrogenic differentiation. Interestingly,
      1 MUm thick solvent cast films are not only capable of hosting an expanding
      population of phenotypically preserved hMSCs similar to tissue culture plastic
      controls, but also the cells detached via temperature control better maintain
      their ability to differentiate compared to conventionally trypsinized cells. This
      approach to hMSC expansion and differentiation can be highly attractive to stem
      cell researchers where clinical therapies have seen a collective deviation away
      from the employment of animal derived products such as proteolytic trypsin.

PMID- 26301715
TI  - Correction: Enterococcus faecalis Glycolipids Modulate Lipoprotein-Content of the
      Bacterial Cell Membrane and Host Immune Response.

PMID- 26301713
TI  - Gene Expression Profiling of Development and Anthocyanin Accumulation in
      Kiwifruit (Actinidia chinensis) Based on Transcriptome Sequencing.
AB  - Red-fleshed kiwifruit (Actinidia chinensis Planch. 'Hongyang') is a promising
      commercial cultivar due to its nutritious value and unique flesh color, derived
      from vitamin C and anthocyanins. In this study, we obtained transcriptome data of
      'Hongyang' from seven developmental stages using Illumina sequencing. We mapped
      39-54 million reads to the recently sequenced kiwifruit genome and other
      databases to define gene structure, to analyze alternative splicing, and to
      quantify gene transcript abundance at different developmental stages. The
      transcript profiles throughout red kiwifruit development were constructed and
      analyzed, with a focus on the biosynthesis and metabolism of compounds such as
      phytohormones, sugars, starch and L-ascorbic acid, which are indispensable for
      the development and formation of quality fruit. Candidate genes for these
      pathways were identified through MapMan and phylogenetic analysis. The transcript
      levels of genes involved in sucrose and starch metabolism were consistent with
      the change in soluble sugar and starch content throughout kiwifruit development.
      The metabolism of L-ascorbic acid was very active, primarily through the L
      galactose pathway. The genes responsible for the accumulation of anthocyanin in
      red kiwifruit were identified, and their expression levels were investigated
      during kiwifruit development. This survey of gene expression during kiwifruit
      development paves the way for further investigation of the development of this
      uniquely colored and nutritious fruit and reveals which factors are needed for
      high quality fruit formation. This transcriptome data and its analysis will be
      useful for improving kiwifruit genome annotation, for basic fruit molecular
      biology research, and for kiwifruit breeding and improvement. 

PMID- 26301717
TI  - When and how to 'FLAMSA-RIC' in acute myeloid leukemia?

PMID- 26301716
TI  - Spatio-Temporal Regularization for Longitudinal Registration to Subject-Specific
      3d Template.
AB  - Neurodegenerative diseases such as Alzheimer's disease present subtle anatomical
      brain changes before the appearance of clinical symptoms. Manual structure
      segmentation is long and tedious and although automatic methods exist, they are
      often performed in a cross-sectional manner where each time-point is analyzed
      independently. With such analysis methods, bias, error and longitudinal noise may
      be introduced. Noise due to MR scanners and other physiological effects may also
      introduce variability in the measurement. We propose to use 4D non-linear
      registration with spatio-temporal regularization to correct for potential
      longitudinal inconsistencies in the context of structure segmentation. The major
      contribution of this article is the use of individual template creation with
      spatio-temporal regularization of the deformation fields for each subject. We
      validate our method with different sets of real MRI data, compare it to available
      longitudinal methods such as FreeSurfer, SPM12, QUARC, TBM, and KNBSI, and
      demonstrate that spatially local temporal regularization yields more consistent
      rates of change of global structures resulting in better statistical power to
      detect significant changes over time and between populations. 

PMID- 26301718
TI  - Western lowland gorilla (Gorilla gorilla gorilla) birth patterns and human
      presence in zoological settings.
AB  - There is some evidence to suggest that zoo visitors may have a disruptive impact
      on zoo-housed animals, especially primates. While some consider western lowland
      gorillas (Gorilla gorilla gorilla) to be particularly reactive to large crowds,
      the evidence of these effects is mixed, and is likely highly influenced by
      exhibit design, and group composition. While the majority of studies have focused
      on behavioral responses to human presence, there is the potential for
      physiological effects as well, including the possibility of affecting the timing
      of parturition. Such effects have been demonstrated in laboratory-housed
      callitrichids and chimpanzees, but unlike laboratory settings where human
      presence is lowest during the weekends, human presence might peak during weekends
      in public zoo settings. However, in a study of zoo-housed chimpanzees, there were
      no significant differences between the number of chimpanzee births that occurred
      on weekdays compared to weekends [Wagner and Ross, 2008], and we sought to test
      these questions with gorillas. We analyzed the timing of 336 live gorilla births
      and 48 stillbirths at 53 accredited North American zoos from 1985-2014, and
      similarly to chimpanzees, found no weekend or weekday effect on number of births
      (live births: G = 0.000, p = 1; stillbirths: G = 0.166, p < 0.684). These data
      add to our understanding of the potential influence of human presence on primate
      behavior and physiology, and add to evidence suggesting that the effects of zoo
      visitors on exhibited species may be less profound than previously assumed.

PMID- 26301719
TI  - The dynamics of temperature and light on the growth of phytoplankton.
AB  - Motivated by some lab and field observations of the hump shaped effects of water
      temperature and light on the growth of phytoplankton, a bottom-up nutrient
      phytoplankton model, which incorporates the combined effects of temperature and
      light, is proposed and analyzed to explore the dynamics of phytoplankton bloom.
      The population growth model reasonably captures such observed dynamics
      qualitatively. An ecological reproductive index is defined to characterize the
      growth of the phytoplankton which also allows a comprehensive analysis of the
      role of temperature and light on the growth and reproductive characteristics of
      phytoplankton in general. The model provides a framework to study the mechanisms
      of phytoplankton dynamics in shallow lake and may even be employed to study the
      controlled phytoplankton bloom. 

PMID- 26301720
TI  - Towards the industrialization of new biosurfactants: Biotechnological
      opportunities for the lactone esterase gene from Starmerella bombicola.
AB  - Although sophorolipids (SLs) produced by S. bombicola are a real showcase for the
      industrialization of microbial biosurfactants, some important drawbacks are
      associated with this efficient biological process, e.g., the simultaneous
      production of acidic and lactonic SLs. Depending on the application, there is a
      requirement for the naturally produced mixture to be manipulated to give defined
      ratios of the components. Recently, the enzyme responsible for the lactonization
      of SLs was discovered. The discovery of the gene encoding this lactone esterase
      (sble) enabled the development of promising S. bombicola strains producing either
      solely lactonic (using a sble overexpression strain described in this paper: oe
      sble) or solely acidic SLs (using a sble deletion strain, which was recently
      described, but not characterized yet: Deltasble). The new S. bombicola strains
      were used to investigate the production processes (fermentation and purification)
      of either lactonic or acidic SLs. The strains maintain the high inherent
      productivities of the wild-type or even perform slightly better and thus
      represent a realistic industrial opportunity. 100% acidic SLs with a mixed
      acetylation pattern were obtained for the Deltasble strain, while the inherent
      capacity to selectively produce lactonic SLs was significantly increased (+42%)
      for the oe sble strain (99% lactonic SLs). Moreover, the regulatory effect of
      citrate on lactone SL formation for the wild-type was absent in this new strain,
      which indicates that it is more robust and better suited for the industrial
      production of lactonic SLs. Basic parameters were determined for the purified
      SLs, which confirm that the two new strains produce molecules with distinctive
      properties of which the application potential can now easily be investigated
      independently.

PMID- 26301721
TI  - Trends in Medicaid Reimbursements for Insulin From 1991 Through 2014.
AB  - IMPORTANCE: Insulin is a vital medicine for patients with diabetes mellitus.
      Newer, more expensive insulin products and the lack of generic insulins in the
      United States have increased costs for patients and insurers. OBJECTIVE: To
      examine Medicaid payment trends for insulin products. Cost information is
      available for all 50 states and has been recorded since the 1990s. DESIGN,
      SETTING, AND PARTICIPANTS: A time-series analysis comparing reimbursements and
      prices. Using state- and national-level Medicaid data from 1991 to 2014, we
      identified all patients who used 1 or more of the 16 insulin products that were
      continuously available in the United States between 2006 and 2014. Insulin
      products were classified into rapid-acting and long-acting analogs, short-acting,
      intermediate, and premixed insulins based on American Diabetes Association
      Guidelines. MAIN OUTCOMES AND MEASURES: Inflation-adjusted payments made to
      pharmacies by Medicaid per 1 mL (100 IU) of insulin in 2014 US dollars. RESULTS:
      Since 1991, Medicaid reimbursement per unit (1 mL) of insulin dispensed has risen
      steadily. In the 1990s, Medicaid reimbursed pharmacies between $2.36 and $4.43
      per unit. By 2014, reimbursement for short-acting insulins increased to $9.64 per
      unit; intermediate, $9.22; premixed, $14.79; and long-acting, $19.78. Medicaid
      reimbursement for rapid-acting insulin analogs rose to $19.81 per unit. The rate
      of increase in reimbursement was higher for insulins with patent protection
      ($0.20 per quarter) than without ($0.05 per quarter) (P<.001).Total Medicaid
      reimbursements peaked at $407.4 million dollars in quarter 2 of 2014. Total
      volume peaked at 29.9 million units in quarter 4 of 2005 and was 21.2 million
      units in quarter 2 of 2014. CONCLUSIONS AND RELEVANCE: Between 1991 and 2014,
      there was a near-exponential upward trend in Medicaid payments on a per-unit
      basis for a wide variety of insulin products regardless of formulation, duration
      of action, and whether the product was patented. Although reimbursements for
      newer, patent-protected insulin analogs increased at a faster rate than
      reimbursements for older insulins, payments increased for all products we
      examined. Our findings suggest a lack of price competition in the United States
      for this class of medications.

PMID- 26301722
TI  - Non-operative management versus operative management in high-grade blunt hepatic
      injury.
AB  - BACKGROUND: Surgery used to be the treatment of choice in cases of blunt hepatic
      injury, but this approach gradually changed over the last two decades as
      increasing non-operative management (NOM) of splenic injury led to its use for
      hepatic injury. The improvement in critical care monitoring and computed
      tomographic scanning, as well as the more frequent use of interventional
      radiology techniques, has helped to bring about this change to non-operative
      management. Liver trauma ranges from a small capsular tear, without parenchymal
      laceration, to massive parenchymal injury with major hepatic vein/retrohepatic
      vena cava lesions. In 1994, the Organ Injury Scaling Committee of the American
      Association for the Surgery of Trauma (AAST) revised the Hepatic Injury Scale to
      have a range from grade I to VI. Minor injuries (grade I or II) are the most
      frequent liver injuries (80% to 90% of all cases); severe injuries are grade III
      V lesions; grade VI lesions are frequently incompatible with survival. In the
      medical literature, the majority of patients who have undergone NOM have low
      grade liver injuries. The safety of NOM in high-grade liver lesions, AAST grade
      IV and V, remains a subject of debate as a high incidence of liver and collateral
      extra-abdominal complications are still described. OBJECTIVES: To assess the
      effects of non-operative management compared to operative management in high
      grade (grade III-V) blunt hepatic injury. SEARCH METHODS: The search for studies
      was run on 14 April 2014. 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 (Ovid), PubMed, ISI WOS (SCI-EXPANDED, SSCI, CPCI-S & CPSI-SSH),
      clinical trials registries, conference proceedings, and we screened reference
      lists. SELECTION CRITERIA: All randomised trials that compare non-operative
      management versus operative management in high-grade blunt hepatic injury. DATA
      COLLECTION AND ANALYSIS: Two authors independently applied the selection criteria
      to relevant study reports. We used standard methodological procedures as defined
      by the Cochrane Collaboration. MAIN RESULTS: We were unable to find any
      randomised controlled trials of non-operative management versus operative
      management in high-grade blunt hepatic injury. AUTHORS' CONCLUSIONS: In order to
      further explore the preliminary findings provided by animal models and
      observational clinical studies that suggests there may be a beneficial effect of
      non-operative management versus operative management in high-grade blunt hepatic
      injury, large, high quality randomised trials are needed.

PMID- 26301723
TI  - The Role of Hypothermia Coordinator: A Case of Hypothermic Cardiac Arrest Treated
      with ECMO.
AB  - We present a description of emergency medical rescue procedures in a patient
      suffering from severe hypothermia who was found in the Babia Gora mountain range
      (Poland). After diagnosing the symptoms of II/III stage hypothermia according to
      the Swiss Staging System, the Mountain Rescue Service notified the coordinator
      from the Severe Accidental Hypothermia Center (CLHG) Coordinator in Krakow and
      then kept in constant touch with him. In accordance with the protocol for
      managing such situations, the coordinator started the procedure for patients in
      severe hypothermia with the option of extracorporeal warming and secured access
      to a device for continuous mechanical chest compression. After reaching the
      hospital, extracorporeal warming with ECMO support in the arteriovenuous
      configuration was started. The total duration of circulatory arrest was 150
      minutes. The rescue procedures were supervised by the coordinator, who was on 24
      hour duty and was reached by means of an alarm phone. The task of the coordinator
      is to consult the management of hypothermia cases, use his knowledge and
      experience to help in the diagnosis and treatment. and if the need arises refer
      the patient for ECMO at CLHG. Good coordination, planning, predicting possible
      problems, and acting in accordance with the agreed procedures in the scheme, make
      it possible to shorten the time of reaching the destination hospital and
      implement effective treatment.

PMID- 26301724
TI  - The Relationship Between Sociodemographic Characteristics and Clinical Features
      in Burning Mouth Syndrome.
AB  - OBJECTIVE: To compare sociodemographic and clinical characteristics in patients
      with burning mouth syndrome (BMS) and their relationship with pain. DESIGN: Cross
      sectional clinical study. SETTING: University-Hospital. SUBJECTS: 75 BMS patients
      were enrolled. METHODS: The study was conducted between September 2011 and March
      2012 at the "Federico II" University of Naples. Demographic characteristics and
      clinical information including age, sex, educational level, marital status, job
      status, age at disease onset, oral symptoms, and triggers were collected via
      questionnaire interviews. To assess pain intensity the visual analogue scale
      (VAS) was administered. Descriptive statistics were collected, and Pearson Chi
      square tests, Kruskal-Wallis nonparametric tests and the Spearman bivariate
      correlation were performed. RESULTS: The mean age was 61.17 (+/-11.75,
      female/male ratio = 3:1). The mean age at disease onset was 56.75 (+/-12.01). A
      low educational level (8.57 +/- 4.95) and 80% of unemployment were found. Job
      status and age at disease onset correlated with the VAS scale (P = 0.019 and P =
      0.015, respectively). Tongue morphology changes, taste disturbances, and
      intraoral foreign body sensation have a significant dependence on gender (P =
      0.049, 0.001, and 0.045, respectively); intraoral foreign body sensation has a
      significant dependence on marital status (P = 0.033); taste disturbances have a
      significant dependence on job status. (P = 0.049); xerostomia has a significant
      dependence on age (P = 0.039); and tongue color changes and a bitter taste have a
      significant dependence on educational level (P = 0.040 and 0.022, respectively).
      Marital status and educational level have a significant dependence on the
      triggers (P = 0.036 and 0.049, respectively). CONCLUSIONS: The prevalence of BMS
      is higher in women, and in married, unemployed, and less highly educated
      patients. Burning is the most frequent symptom while stressful life events are
      the most frequent trigger reported.

PMID- 26301725
TI  - Measuring how genetic and epigenetic variants can filter emotion perception.
AB  - Emotion perception has been extensively studied in cognitive neurosciences and
      stands as a promising intermediate phenotype of social cognitive processes and
      psychopathologies. Exciting imaging genetic studies have recently identified
      genetic and epigenetic variants affecting brain responses during emotion
      perception tasks, but characterizing how these variants interact and relate to
      higher-order cognitive processes remains a challenge. Here, we integrate works in
      parallel fields and propose a new psychophysical conceptualization to address
      this issue. This approach proposes to consider genetic variants as 'filters' of
      perceptual information that can interact to shape different perceptual profiles.
      Importantly, these perceptual profiles can be precisely described and compared
      between multivariate genetic groups using a new psychophysical method. Crucially,
      this approach represents a potentially powerful novel tool to address gene-by
      gene and gene-by-environment interactions, and provides a new cognitive
      perspective to link social perceptive and social cognitive processes in the
      context of psychiatric disorders. 

PMID- 26301726
TI  - Synthesis of Fijiolide A via an Atropselective Paracyclophane Formation.
AB  - Fijiolide A is a secondary metabolite isolated from a marine-derived actinomycete
      and displays inhibitory activity against TNF-alpha-induced activation of
      NFkappaB, an important transcription factor and a potential target for the
      treatment of different cancers and inflammation related diseases. Fijiolide A is
      a glycosylated complex paracyclophane, which is structurally closely related to
      the Bergman-aromatization product of enediyne C-1027. We report an
      enantioselective synthesis of fijiolide A demonstrating the power of fully
      intermolecular ruthenium-catalyzed [2 + 2 + 2]-cyclotrimerizations with three
      different alkynes to assemble the heavily substituted central arene core. The
      characteristic strained [2.6]paracyclophane structure is accessed by a templated
      atropselective macroetherification reaction. 

PMID- 26301727
TI  - Total Synthesis of Prostaglandin 15d-PGJ(2) and Investigation of its Effect on
      the Secretion of IL-6 and IL-12.
AB  - An efficient synthesis of 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2, 1) is
      reported. The route described allows for diversification of the parent structure
      to prepare seven analogues of 1 in which the positioning of electrophilic sites
      is varied. These analogues were tested in SAR studies for their ability to reduce
      the secretion of proinflammatory cytokines. It was shown that the endocyclic
      enone is crucial for the bioactivity investigated and that the conjugated omega
      side chain serves in a reinforcing manner. 

PMID- 26301728
TI  - The focal account: Indirect lie detection need not access unconscious, implicit
      knowledge.
AB  - People are poor lie detectors, but accuracy can be improved by making the
      judgment indirectly. In a typical demonstration, participants are not told that
      the experiment is about deception at all. Instead, they judge whether the speaker
      appears, say, tense or not. Surprisingly, these indirect judgments better reflect
      the speaker's veracity. A common explanation is that participants have an
      implicit awareness of deceptive behavior, even when they cannot explicitly
      identify it. We propose an alternative explanation. Attending to a range of
      behaviors, as explicit raters do, can lead to conflict: A speaker may be thinking
      hard (indicating deception) but not tense (indicating honesty). In 2 experiments,
      we show that the judgment (and in turn the correct classification rate) is the
      result of attending to a single behavior, as indirect raters are instructed to
      do. Indirect lie detection does not access implicit knowledge, but simply focuses
      the perceiver on more useful cues.

PMID- 26301729
TI  - Upper limit of magnetic effect on alpha/beta ratio.
AB  - Magnetic resonance imaging (MRI) is being integrated into radiotherapy delivery
      for MRI-guided radiotherapy. The purpose of this work is to investigate
      theoretically the upper limit of any potential magnetic effect on the alpha/beta
      ratio, an important radiobiological parameter in radiation therapy. Based on the
      theory of dual radiation action, the alpha/beta ratio can be expressed by an
      integral of the product of two microdosimetry quantities (x) and t(x), where (x)
      is the probability that two energy transfers, a distance x apart, results in a
      lesion, and t(x) is the proximity function, which is the energy-weighted
      pointpair distribution of distances between energy transfer points in a track.
      The quantity t(x) depends on the applied magnetic field. An analytical approach
      has been used to derive a formula that can be used to calculate the alpha/beta
      ratio in an extremely strong magnetic field, which gives the upper limit of the
      potential changes of the alpha/beta ratio due to the presence of a magnetic
      field. For V79 Chinese hamster cells the upper limit of the increase of the
      alpha/beta ratio with a magnetic field has been found to be 2.90 times for Pd
      103, 2.97 times for I-125 and 2.3 times for Co-60 sources.

PMID- 26301733
TI  - Understanding Bayesian Statistics.
AB  - Modern computing power has given us the ability to approach statistical questions
      in a manner which was previously impossible because of the time-consuming nature
      of the calculations required. Computer power has enabled the use of Bayesian
      inference techniques, based on 18th century theory, to frame statistical
      questions in probability. 

PMID- 26301734
TI  - Hospital-Based Violence Prevention: Progress and Opportunities.

PMID- 26301735
TI  - Choice of ICD-10 codes for the identification of acute coronary syndrome in the
      French hospitalization database.
AB  - The objective of this study was to evaluate the performance of the ICD-10
      (International Classification of Diseases and Related Health Problems, 10(th)
      Edition) coding in the French hospitalization database (PMSI) to identify acute
      coronary syndrome (ACS) occurrence. Eligible hospitalizations were those that
      occurred at the Bordeaux teaching hospitals between 1 January 2011 and 31
      December 2011 and had one of the ICD-10 codes related to ischaemic heart diseases
      (I20 to I25, excluding I23 and I25.2). Among these, 100 hospitalizations were
      randomly selected; for each case, the ACS diagnosis was confirmed/excluded after
      medical file examination by an independent events validation committee and the
      performance of codes, and combinations of codes, to identify ACS was evaluated by
      calculating the positive predictive value (PPV). Of the individual codes, I20.0,
      I21 and I24 had the highest PPV; 100.0% for I24 (95%CI [15.8-100.0]); 90.0% for
      I21 (95%CI [76.3-97.2]); and 66.7% for I20.0 (95%CI [38.4-88.2]). The combination
      of I20.0 or I24 codes was able to identify 12 of the 56 validated ACS cases with
      a PPV of 70.6% (95%CI [44.0-89.7]), the combination of I21 or I24 identified 38
      cases with a PPV of 90.5% (95%CI [77.4-97.3]), the combination of I20.0 or I21
      identified 46 cases with a PPV of 83.6% (95%CI [71.2-92.2]), and the combination
      of I20.0, I21 or I24 identified 48 cases with a PPV of 84.2% (95%CI [72.1-92.5]).
      The combination of I20.0, I21 or I24 codes had the best performance to identify
      occurrence of ACS in the French hospitalization database. 

PMID- 26301737
TI  - Frequency, severity, and risk factors related to sexual dysfunction in Chinese
      women with T2D.
AB  - BACKGROUND: The aim of the present study was to assess the frequency and severity
      of female sexual dysfunction (FSD) in those with T2D (T2D) compared with non
      diabetic controls. In addition, risk factors for FSD were analyzed. METHODS:
      Sexual dysfunction, measured using the Female Sexual Function Index (FSFI), was
      evaluated using a questionnaire in 184 women with T2D and 146 non-diabetic
      controls at three study sites in China. In the T2D group, FSD was examined by
      education level, correlations between FSD and other variables were analyzed, and
      risk factors were studied. RESULTS: The frequency of FSD in the T2D group was
      75.0%, much higher than in the control group (56.2%; P = 0.001). The severity of
      FSD in the T2D group was 17.84 +/- 8.47 (mean +/- SD), significantly lower than
      in the control group (21.14 +/- 8.08; P = 0.001). In patients with T2D, being
      older (P = 0.001), taking oral antidiabetic medications (P = 0.013), and having
      diabetic neuropathy (P = 0.036) were risk factors for FSD. CONCLUSIONS: The rate
      of FSD is high in China and, as seen in the literature, more severe in diabetics
      than non-diabetics. Being older, taking oral antidiabetic medications, and
      diabetic neuropathy are risk factors for FSD.

PMID- 26301738
TI  - Tradeoffs between income, air pollution and life expectancy: Brief report on the
      US experience, 1980-2000.
AB  - During the period of 1980-2000, the US obtained substantial reductions in air
      pollution and improvements in life expectancy (LE). Multiple factors contributed
      to improved health. This report explores and illustrates trade-offs between
      income, air pollution, and LE. Both improved air quality and income growth
      contributed to LE gains - without evidence of substantial negative tradeoffs
      between air pollution and income. Cleaner air may be considered an "economic
      good" with contributions to health, wellbeing, and human capital. 

PMID- 26301736
TI  - Structure-Based Design of a Small Molecule CD4-Antagonist with Broad Spectrum
      Anti-HIV-1 Activity.
AB  - Earlier we reported the discovery and design of NBD-556 and their analogs which
      demonstrated their potential as HIV-1 entry inhibitors. However, progress in
      developing these inhibitors has been stymied by their CD4-agonist properties, an
      unfavorable trait for use as drug. Here, we demonstrate the successful conversion
      of a full CD4-agonist (NBD-556) through a partial CD4-agonist (NBD-09027), to a
      full CD4-antagonist (NBD-11021) by structure-based modification of the critical
      oxalamide midregion, previously thought to be intolerant of modification. NBD
      11021 showed unprecedented neutralization breath for this class of inhibitors,
      with pan-neutralization against a panel of 56 Env-pseudotyped HIV-1 representing
      diverse subtypes of clinical isolates (IC50 as low as 270 nM). The cocrystal
      structure of NBD-11021 complexed to a monomeric HIV-1 gp120 core revealed its
      detail binding characteristics. The study is expected to provide a framework for
      further development of NBD series as HIV-1 entry inhibitors for clinical
      application against AIDS. 

PMID- 26301739
TI  - Obesity and excess weight in early adulthood and high risks of arsenic-related
      cancer in later life.
AB  - BACKGROUND: Elevated body mass index (BMI) is a risk factor for cardiovascular
      disease, diabetes, cancer, and other diseases. Inflammation or oxidative stress
      induced by high BMI may explain some of these effects. Millions of people drink
      arsenic-contaminated water worldwide, and ingested arsenic has also been
      associated with inflammation, oxidative stress, and cancer. OBJECTIVES: To assess
      the unique situation of people living in northern Chile exposed to high arsenic
      concentrations in drinking water and investigate interactions between arsenic and
      BMI, and associations with lung and bladder cancer risks. METHODS: Information on
      self-reported body mass index (BMI) at various life stages, smoking, diet, and
      lifetime arsenic exposure was collected from 532 cancer cases and 634 population
      based controls. RESULTS: In subjects with BMIs <90th percentile in early
      adulthood (27.7 and 28.6 kg/m(2) in males and females, respectively), odds ratios
      (OR) for lung and bladder cancer combined for arsenic concentrations of <100, 100
      800 and >800 ug/L were 1.00, 1.64 (95% CI, 1.19-2.27), and 3.12 (2.30-4.22). In
      subjects with BMIs >=90th percentile in early adulthood, the corresponding ORs
      were higher: 1.00, 1.84 (0.75-4.52), and 9.37 (2.88-30.53), respectively (synergy
      index=4.05, 95% CI, 1.27-12.88). Arsenic-related cancer ORs >20 were seen in
      those with elevated BMIs in both early adulthood and in later life. Adjustments
      for smoking, diet, and other factors had little impact. CONCLUSION: These
      findings provide novel preliminary evidence supporting the notion that
      environmentally-related cancer risks may be markedly increased in people with
      elevated BMIs, especially in those with an elevated BMI in early-life.

PMID- 26301740
TI  - Prenatal exposure to polycyclic aromatic hydrocarbons/aromatics, BDNF and child
      development.
AB  - OBJECTIVES: Within a New York City (NYC) birth cohort, we assessed the
      associations between polycyclic aromatic hydrocarbon (PAH) and other aromatic DNA
      adducts and brain derived neurotrophic factor (BDNF) concentrations in umbilical
      cord blood, and neurodevelopment at age 2 years and whether BDNF is a mediator of
      the associations between PAH/aromatic-DNA adducts and neurodevelopment. METHODS:
      PAH/aromatic-DNA adduct concentrations in cord blood were measured in 505
      children born to nonsmoking African-American and Dominican women residing in NYC,
      and a subset was assessed for neurodevelopment at 2 years using the Bayley Scales
      of Infant Development Mental Development Index (MDI). A spectrum of PAH/aromatic
      DNA adducts was measured using the (32)P-postlabeling assay; DNA adducts formed
      by benzo[a]pyrene (B[a]P), a representative PAH, were measured by High
      Performance Liquid Chromatography (HPLC)/fluorescence. BDNF mature protein in
      cord blood plasma was quantified by an ELISA. Multivariate regression analysis,
      adjusting for potential confounders, was conducted. RESULTS: PAH/aromatic-DNA
      adduct concentration measured by postlabeling was inversely associated with BDNF
      concentration (p=0.02) and with MDI scores at 2 years (p=0.04). BDNF level was
      positively associated with MDI scores (p=0.003). Restricting to subjects having
      all three measures (PAH/aromatic-DNA adducts by postlabeling, MDI, and BDNF),
      results were similar but attenuated (p=0.13, p=0.05, p=0.01, respectively).
      Associations between B[a]P-DNA adducts and BDNF and B[a]P-DNA adducts and MDI at
      age 2 years were not significant. At age 3 years, the positive association of
      BDNF with MDI was not observed. CONCLUSIONS: The results at age 2 suggest that
      prenatal exposure to a spectrum of PAH/aromatic pollutants may adversely affect
      early neurodevelopment, in part by reducing BDNF levels during the fetal period.
      However, the same relationship was not seen at age 3.

PMID- 26301742
TI  - Formation Dynamics of Oral Oil Coatings and Their Effect on Subsequent Sweetness
      Perception of Liquid Stimuli.
AB  - Knowledge of the formation of oral coatings and their influence on subsequent
      taste perception is necessary to understand possible taste-masking effects by oil
      coatings. This study investigated (a) the dynamics of the formation of oral oil
      coatings formed by o/w emulsions and (b) the effect of oral oil coatings on
      subsequent sweetness perception of sucrose solutions. In vivo fluorescence was
      used to quantitate the oil fraction deposited on the tongue after oral processing
      of oil-in-water emulsions for different times. A trained panel evaluated
      sweetness perception of sucrose solutions after orally processing the emulsions.
      The oil fraction reached its maximum value within the first 3 s of oral
      processing. The oil fraction did not significantly affect subsequent sweetness
      perception of sucrose solutions. It is suggested that the oil droplets deposited
      on the tongue did not form a hydrophobic barrier that is sufficient to reduce the
      accessibility of sucrose to taste buds. 

PMID- 26301743
TI  - Toward Prediction of the Chemistry in Ionic Liquids: An Accurate Computation of
      Absolute pK(a) Values of Benzoic Acids and Benzenethiols.
AB  - In contrast to the great success of computational methodologies in molecular
      solvents, effective and accurate calculation of the fundamental bond energetic
      properties in ionic liquids (ILs) is essentially absent. This is largely due to
      the unusual complexity of handling solvation quantities of ILs and the lack of
      precisely determined bond parameters to serve as the authentic benchmark to
      calibrate the modeling methodology. Herein, we report the first accurate
      calculations of absolute pK(a) values in a commonly used IL, [Bmim][NTf2], with
      the carefully developed "ion-biased" cluster-continuum model. Experimental pK(a)
      values of benzoic acids and benzenethiols in [Bmim][NTf2] were reproduced with
      mean unsigned errors of only 0.3 and 0.5 pK(a) units, respectively, which enables
      theoretical approaches with a suitable strategy as a powerful tool to handle
      complicated problems in ILs and to eventually realize the rational design of the
      IL chemistry.

PMID- 26301741
TI  - The impact of peri-operative blood transfusions on post-pancreatectomy short-term
      outcomes: an analysis from the American College of Surgeons National Surgical
      Quality Improvement Program.
AB  - BACKGROUND: Peri-operative red blood cell transfusions (RBCT) may induce
      transfusion-related immunomodulation and impact post-operative recovery. This
      study examined the association between RBCT and post-pancreatectomy morbidity.
      METHODS: Using the American College of Surgeons National Surgical Quality
      Improvement Program (ACS-NSQIP) registry, patients undergoing an elective
      pancreatectomy (2007-2012) were identified. Patients with missing data on key
      variables were excluded. Primary outcomes were 30-day post-operative major
      morbidity, mortality, and length of stay (LOS). Unadjusted and adjusted relative
      risks (RR) with a 95% confidence interval (95%CI) were computed using modified
      Poisson, logistic, or negative binomial regression, to estimate the association
      between RBCT and outcomes. RESULTS: The database included 21 132 patients who had
      a pancreatectomy during the study period. Seventeen thousand five hundred and
      twenty-three patients were included, and 4672 (26.7%) received RBCT. After
      adjustment for baseline and clinical characteristics, including comorbidities,
      malignant diagnosis, procedure and operative time, RBCT was independently
      associated with increased major morbidity (RR 1.49; 95% CI: 1.39-1.60), mortality
      (RR 2.19; 95%CI: 1.76-2.73) and LOS (RR 1.27; 95%CI 1.24-1.29). CONCLUSION: Peri
      operative RBCT for a pancreatectomy was independently associated with worse short
      term outcomes and prolonged LOS. Future studies should focus on the impact of
      interventions to minimize the use of RBCT after an elective pancreatectomy.

PMID- 26301744
TI  - Butanolysis derivatization: improved sensitivity in LC-MS/MS quantitation of
      heparan sulfate in urine from mucopolysaccharidosis patients.
AB  - Heparan sulfate (HS) is a complex oligosaccharide that is a marker of a number of
      diseases, most notably several of the mucopolysaccharidoses (MPS). It is a very
      heterogeneous compound and its quantification at physiological concentrations in
      patient samples is challenging. Here, we demonstrate novel derivatization
      chemistry for depolymerization/desulfation and alkylation of HS based on
      butanolysis. The resultant alkylated disaccharides are quantifiable by LC-MS/MS.
      This new method is at least 70-fold more sensitive than a previously published
      methanolysis method. Disaccharide yield over time is compared for methanolysis,
      ethanolysis, and butanolysis. Maximum disaccharide concentration was observed
      after 2 h with butanolysis and 18 h with ethanolysis whereas a maximum was not
      reached over the 24 h of the experiment with methanolysis. The sensitivity of the
      new technique is illustrated by the quantification of HS in 5 MUL urine samples
      from MPS patients and healthy controls. HS was quantifiable in all samples
      including controls. Disaccharide reaction products were further characterized
      using exact mass MS/MS. 

PMID- 26301745
TI  - Transport and uptake of clausenamide enantiomers in CYP3A4-transfected Caco-2
      cells: An insight into the efflux-metabolism alliance.
AB  - The present study developed a CYP3A4-expressed Caco-2 monolayer model at which
      effects of the efflux-metabolism alliance on the transport and uptake of
      clausenamide (CLA) enantiomers as CYP3A4 substrates were investigated. The
      apparent permeability coefficients (Papp) of (-) and (+)CLA were higher in the
      absorptive direction than those in the secretory direction with efflux ratios
      (ER) of 0.709+/-0.411 and 0.867+/-0.250 (*10(-6)cm/s), respectively. Their
      bidirectional transports were significantly reduced by 75.6-87.5% after treatment
      with verapamil (a P-glycoprotein inhibitor) that increased the rate of metabolism
      by CYP3A4, whereas the CYP3A4 inhibitor ketoconazole treatment markedly enhanced
      the basolateral to apical flux of (-) and (+)CLA with ERs being 2.934+/-1.432 and
      1.877+/-0.148(*10(-6)cm/s) respectively. These changes could be blocked by the
      duel CYP3A4/P-glycoprotein inhibitor cyclosporine A, consequently, Papp values
      for CLA enantiomers in both directions were significantly greater than those
      obtained by using verapamil or ketoconazole, and their ERs were similar to those
      following (-) or (+)-isomer treatment alone. Furthermore, the uptake of (-)CLA
      was more than that of (+)CLA in the transfected cells. Incubation with
      ketoconazole decreased the intracellular concentrations of the two enantiomers.
      This effect disappeared in the presence of a CYP3A4 inducer dexamethasone. These
      results indicated that CYP3A4 could influence P-gp efflux, transport and uptake
      of CLA enantiomers as CYP3A4 substrates and that a duel inhibition to CYP3A4/ P
      glycoprotein could enhance their absorption and bioavailability, which provides
      new insight into the efflux-metabolism alliance and will benefit the clinical
      pharmacology of (-)CLA as a candidate drug for treatment of Alzheimer's disease. 

PMID- 26301747
TI  - Lower serum amylase in A blood type relative to O blood type in a general
      Japanese adult population.

PMID- 26301746
TI  - Addressing Palliative Sedation during Expert Consultation: A Descriptive Analysis
      of the Practice of Dutch Palliative Care Consultation Teams.
AB  - MAIN OBJECTIVE: Since palliative sedation is considered a complex intervention,
      consultation teams are increasingly established to support general practice. This
      study aims to offer insight into the frequency and characteristics of expert
      consultations regarding palliative sedation. METHODS: We performed a
      retrospective analysis of a longitudinal database. This database contained all
      patient-related consultations by Dutch Palliative Care Consultation teams, that
      were requested between 2004 and 2011. We described the frequency and
      characteristics of these consultations, in particular of the subgroup of
      consultations in which palliative sedation was addressed (i.e. PSa
      consultations). We used multivariate regression analysis to explore consultation
      characteristics associated with a higher likelihood of PSa consultations. MAIN
      RESULTS AND THEIR SIGNIFICANCE: Of the 44,443 initial consultations, most were
      requested by general practitioners (73%) and most concerned patients with cancer
      (86%). Palliative sedation was addressed in 18.1% of all consultations.
      Palliative sedation was relatively more often discussed during consultations for
      patients with a neurologic disease (OR 1.79; 95% CI: 1.51-2.12) or COPD (OR 1.39;
      95% CI: 1.15-1.69) than for patients with cancer. We observed a higher likelihood
      of PSa consultations if the following topics were also addressed during
      consultation: dyspnoea (OR 1.30; 95% CI: 1.22-1.40), agitation/delirium (OR 1.57;
      95% CI: 1.47-1.68), exhaustion (OR 2.89; 95% CI: 2.61-3.20), euthanasia-related
      questions (OR 2.65; 95% CI: 2.37-2.96) or existential issues (OR 1.55; 95% CI:
      1.31-1.83). CONCLUSION: In conclusion, PSa consultations accounted for almost one
      fifth of all expert consultations and were associated with several case-related
      characteristics. These characteristics may help clinicians in identifying
      patients at risk for a more complex disease trajectory at the end of life.

PMID- 26301748
TI  - Patient and Provider Reported Reasons for Lost to Follow Up in MDRTB Treatment: A
      Qualitative Study from a Drug Resistant TB Centre in India.
AB  - INTRODUCTION: Multidrug-resistant Tuberculosis (MDR TB) is emerging public health
      concern globally. Lost to follow-up (LTFU) is one of the key challenge in MDRTB
      treatment. In 2013, 18% of MDR TB patients were reported LTFU in India. A
      qualitative study was conducted to obtain better understanding of both patient
      and provider related factors for LTFU among MDR TB treatment. METHODS:
      Qualitative semi-structured personal interviews were conducted with 20 MDRTB
      patients reported as LTFU and 10 treatment providers in seven districts linked to
      Nagpur Drug resistant TB Centre (DRTBC) during August 2012-February 2013.
      Interviews were transcribed and inductive content analysis was performed to
      derive emergent themes. RESULTS: We found multiple factors influencing MDR TB
      treatment adherence. Barriers to treatment adherence included drug side effects,
      a perceived lack of provider support, patient financial constraints, conflicts
      with the timing of treatment services, alcoholism and social stigma. CONCLUSIONS:
      Patient adherence to treatment is multi-factorial and involves individual patient
      factors, provider factors, and community factors. Addressing issue of LTFU during
      MDRTB treatment requires enhanced efforts towards resolving medical problems like
      adverse drug effects, developing short duration treatment regimens, reducing pill
      burden, motivational counselling, flexible timings for DOT services, social,
      family support for patients & improving awareness about disease.

PMID- 26301750
TI  - Do non-body donors understand what the term "Body donation" really means?

PMID- 26301749
TI  - Dyskerin and TERC expression may condition survival in lung cancer patients.
AB  - Dyskerin mediates both the modification of uridine on ribosomal and small nuclear
      RNAs and the stabilization of the telomerase RNA component (TERC). In human
      tumors dyskerin expression was found to be associated with both rRNA modification
      and TERC levels. Moreover, dyskerin overexpression has been linked to unfavorable
      prognosis in a variety of tumor types, however an explanation for the latter
      association is not available. To clarify this point, we analyzed the connection
      between dyskerin expression, TERC levels and clinical outcome in two series of
      primary lung cancers, differing for the presence of TERC gene amplification, a
      genetic alteration inducing strong TERC overexpression. TERC levels were
      significantly higher in tumors bearing TERC gene amplification (P = 0.017). In
      addition, the well-established association between dyskerin expression and TERC
      levels was observed only in the series without TERC gene amplification (P =
      0.003), while it was not present in TERC amplified tumors (P = 0.929). Similarly,
      the association between dyskerin expression and survival was found in cases not
      bearing TERC gene amplification (P = 0.009) and was not observed in TERC
      amplified tumors (P = 0.584). These results indicate that the influence of
      dyskerin expression on tumor clinical outcome is linked to its role on the
      maintenance of high levels of TERC. 

PMID- 26301751
TI  - UV-Induced Micropatterning of Complex Functional Surfaces by Photopolymerization
      Controlled by Alkoxyamines.
AB  - We report on the use of an alkoxyamine (AA) for fabrication of functional
      micropatterns with complex structures by UV mask lithography. The living
      character of the polymer surface and the vertical spatial control of the
      repolymerization reaction from few tens of nanometers to few micrometers were
      demonstrated. The impact of the main parameters governing the controlled
      polymerization and the reinitiation process activated by light or heat was
      investigated. Micropatterning is shown to be a powerful method to investigate the
      physicochemical molecular phenomena. It is possible to control the polymer
      microstructure thickness from few tens of nanometers to few micrometers. In the
      last section, some applications are provided showing the potential of the AA for
      generating covalently bonded hydrophilic/hydrophobic micropatterns or luminescent
      surfaces. This demonstrates the high versatility and interest of this route. 

PMID- 26301752
TI  - Risk factors for persistent delinquent behavior among juveniles: A meta-analytic
      review.
AB  - Multiple risk domains have been identified for life-course persistent (LCP)
      offending, but a quantitative review of the effect of different risk domains was
      not yet available. Therefore, we performed a series of multilevel meta-analyses
      to examine the effect of several risk domains for LCP offending relative to
      adolescence-limited (AL) offending. We included 55 studies reporting on 1014
      effects of risk factors, and classified each factor into one of 14 risk domains.
      The results revealed a significant effect for 11 domains ranging from d=0.200 to
      d=0.758. Relatively large effects were found for the criminal history, aggressive
      behavior, and alcohol/drug abuse domains, whereas relatively small effects were
      found for the family, neurocognitive, and attitude domains. The physical health,
      background, and neighborhood domains yielded no effect. Moderator analyses showed
      that effects of sibling-related risk factors were larger than effects of mother
      related risk factors, and that the effect of the relationship domain was largest
      during childhood. We conclude that most risk domains contribute to the
      development of LCP offending and that differences between AL and LCP offenders
      may be quantitative rather than qualitative. Implications of the present results
      for risk assessment and the prevention/treatment of LCP offending are discussed. 

PMID- 26301754
TI  - Conformation of Novel Azo-Dyes Bearing End-Capped Oligo(ethylene glycol) Studied
      by UV-vis and NMR Spectroscopy.
AB  - Two novel azo-dyes bearing an end-capped oligo(ethylene glycol) chain were
      synthesized and then studied by UV-visible and NMR spectroscopy. For both
      azobenzenes, the end-capped oligo(ethylene glycol) segment is on the para
      position of the first phenyl ring. On the second phenyl ring, a methoxy group is
      added on the para position for one azo-dye and no substitution group on the
      other, which made them electronically a push-push and a push system,
      respectively. The presence of the methoxy group changes significantly the
      absorption and the photoisomerization behaviors and results in a much less
      intense absorbance for the trans isomer and a shift from 350 to 360 nm. In the
      kinetic studies the azobenzene bearing a methoxy group shows a zero-order and a
      first-order kinetics as a function of the time scale of the study as well as an
      aggregation phenomenon. This azo-dye in different solvents has been studied by
      (1)H NMR and pulsed gradient NMR experiments to understand the effects of the
      photoisomerization and the aggregation on the self-diffusion of these molecules
      in solutions. 

PMID- 26301753
TI  - Structural analysis of quazepam metabolites in bile by ion trap time-of-flight
      mass spectrometry.
AB  - Quazepam (QZP) is a long-acting benzodiazepine-type hypnotic. We searched for
      novel QZP metabolites in bile and determined their structures by liquid
      chromatography-ion trap time-of-flight mass spectrometry (LC-IT-TOF MS). The
      metabolites were extracted with ethyl acetate after beta-glucuronidase treatment.
      First, a single MS spectrum was acquired. Second, MS(n) spectra were acquired for
      peaks that consisted of ions with the isotope pattern corresponding to molecules
      bearing one chlorine atom. The novel QZP metabolites found in this study were
      hydroxyquazepam, hydroxy-methoxyquazepam, hydroxy-oxoquazepam, and hydroxy
      methoxy-oxoquazepam, which have the hydroxy and methoxy groups on the
      fluorophenyl group, and dihydroxy-oxoquazepam and dihydroxy-methoxy-oxoquazepam,
      which have one hydroxy group at the 3-position of the seven-membered ring and the
      other hydroxy group and the methoxy group on the fluorophenyl group. We
      demonstrated that LC-IT-TOF MS was a useful tool for determining the structure of
      the metabolites. However, the exact locations of the hydroxy and methoxy groups
      on the fluorophenyl group could not be identified. 

PMID- 26301755
TI  - Avoidant decision-making in social anxiety disorder: A laboratory task linked to
      in vivo anxiety and treatment outcome.
AB  - Recent studies on reward-based decision-making in the presence of anxiety-related
      stimuli demonstrated that approach-avoidance conflicts can be assessed under
      controlled laboratory conditions. However, the clinical relevance of these
      decision conflicts has not been demonstrated. To this end, the present study
      investigated avoidant decisions in treatment-seeking individuals with social
      anxiety disorder (SAD). In a gambling task, advantageous choices to maximize
      gains were associated with task-irrelevant angry faces and disadvantageous
      choices with happy faces. The clinical relevance of avoidant decisions for in
      vivo anxiety in a social stress situation (public speaking) were examined (n =
      44). In a subsample (n = 20), the predictive value for a reduction of avoidance
      following behavioral therapy was also evaluated. Results indicated a close link
      between more frequent avoidant decisions and elevated in vivo anxiety. Moreover,
      individuals who showed a deficit in the goal-directed adjustment of their
      decisions also showed higher and sustained distress during the social stressor
      and reported less decrease of avoidance following treatment. The findings
      highlight the importance of an avoidant decision-making style for the experience
      of acute distress and the maintenance of avoidance in SAD. Assessing avoidant
      decision-making may help to predict the response to behavioral treatments.

PMID- 26301757
TI  - Halide-Nitrogen Gas-Phase Clusters: Anion Photoelectron Spectroscopy and High
      Level ab Initio Calculations.
AB  - The gas phase anion photoelectron spectra are presented for the halide-nitrogen
      clusters X(-)...(N2)n, where X = Br and I and n <= 5. Electron binding energies
      for each cluster in the halide series are determined, with no evidence observed
      for first solvation shell closure in either series. High level ab initio
      calculations at the CCSD(T) level of theory are presented for the anion and
      neutral halogen-nitrogen complexes. For the anion species, two minima are
      predicted corresponding to a loosely bound C2v "T-shaped" species and to a higher
      energy covalently bound "triangle" C2v symmetry geometry. For the neutral
      species, three stationary points were located, two of which display similar form
      to the anion minima and a third which is linear, i.e., Cinfinityv symmetry. The
      "T-shaped" geometry is a transition state linking equivalent Cinfinityv symmetry
      minima. Cluster dissociation energies (D0) were determined, for both anion and
      neutral global minima at the CCSD(T) complete basis set limit, to be 7.8 kJ mol(
      1) and 7.0 kJ mol(-1) and 3.5 kJ mol(-1) and 5.0 kJ mol(-1) for the bromine and
      iodine species, respectively. 

PMID- 26301756
TI  - Computerised CBT for depressed adolescents: Randomised controlled trial.
AB  - BACKGROUND: Depression in adolescents is a common and impairing problem.
      Effective psychological therapies for depression are not accessed by most
      adolescents. Computerised therapy offers huge potential for improving access to
      treatment. AIMS: To test the efficacy of Stressbusters, a Computerised-CBT (C
      CBT) programme for depression in young people. METHOD: Multi-site, schools-based,
      RCT of C-CBT compared to Waiting List, for young people (N = 112; aged 12-16)
      with significant symptoms of depression, using multiple-informants (adolescents,
      parents, teachers), with follow-up at 3 and 6 months. RESULTS: Relative to being
      on a Waiting List, C-CBT was associated with statistically significant and
      clinically meaningful improvements in symptoms of depression and anxiety
      according to adolescent self-report; and with a trend towards improvements in
      depression and anxiety according to parent-report. Improvements were maintained
      at follow-up. Treatment gains were similar for boys and girls across the
      participating age range. Treatment effect was partially mediated by changes in
      ruminative thinking. Teachers rated adolescents as having few emotional or
      behavioural problems, both before and after intervention. C-CBT had no detectable
      effect on academic attainment. In the month after intervention, young people who
      received C-CBT had significantly fewer absences from school than those on the
      Waiting List. CONCLUSIONS: C-CBT shows considerable promise for the treatment of
      mild-moderate depression in adolescents.

PMID- 26301758
TI  - Assessing Psychodynamic Conflict.
AB  - Psychodynamic psychotherapies suggest that symptomatic relief is provided, in
      part, with the resolution of psychic conflicts. Clinical researchers have used
      innovative methods to investigate such phenomenon. This article aims to review
      the literature on quantitative psychodynamic conflict rating scales. An
      electronic search of the literature was conducted to retrieve quantitative
      observer-rated scales used to assess conflict noting each measure's theoretical
      model, information source, and training and clinical experience required. Scales
      were also examined for levels of reliability and validity. Five quantitative
      observer-rated conflict scales were identified. Reliability varied from poor to
      excellent with each measure demonstrating good validity. However a small number
      of studies and limited links to current conflict theory suggest further clinical
      research is needed. 

PMID- 26301759
TI  - How Clinicians Feel about Working with Spouses of the Chronically Ill.
AB  - Clinicians who provide psychotherapy to spouses or partners of the chronically
      ill were solicited through listserves of psychodynamic and other organizations.
      The current report excluded those therapists working with spouses of dementia
      patients. Interviews were conducted with clinicians who responded. The interviews
      highlight the challenges commonly encountered by psychotherapeutic work with this
      cohort of therapy patients. A comparison is drawn that shows both overlap and
      distinctions between the experiences of those therapists engaging with spouses of
      chronically ill patients without a dementing process and those working with
      spouses of chronically ill patients who do suffer from a dementing process. 

PMID- 26301760
TI  - Essential Psychoanalysis: Toward a Re-Appraisal of the Relationship between
      Psychoanalysis and Dynamic Psychotherapy.
AB  - Freud stated that any line of investigation which recognizes transference and
      resistance, regardless of its results, was entitled to call itself psychoanalysis
      (Freud, 1914a, p. 16). Separately he wrote that psychoanalysis was the science of
      unconscious mental processes (Freud, 1925, p. 70). Combining these two ideas
      defines Essential Psychoanalysis: Any line of treatment, theory, or science which
      recognizes the facts of unconscious, transference, or resistance, and takes them
      as the starting point of its work, regardless of its results, is psychoanalysis.
      Freud formulated two conflicting definitions of psychoanalysis: Essential
      Psychoanalysis, applicable to all analysts regardless of their individuality and
      Extensive Psychoanalysis, modeled on his individuality. They differ in how
      psychoanalytic technique is viewed. For Essential Psychoanalysis, flexible
      recommendations constitute psychoanalytic technique, whereas for Extensive
      Psychoanalysis, rules constitute a key part of psychoanalytic technique. 

PMID- 26301761
TI  - Contemporary Cognitive Behavior Therapy: A Review of Theory, History, and
      Evidence.
AB  - Cognitive behavior therapy (CBT) has come to be a widely practiced psychotherapy
      throughout the world. The present article reviews theory, history, and evidence
      for CBT. It is meant as an effort to summarize the forms and scope of CBT to date
      for the uninitiated. Elements of CBT such as cognitive therapy, behavior therapy,
      and so-called "third wave" CBT, such as dialectical behavior therapy (DBT) and
      acceptance and commitment therapy (ACT) are covered. The evidence for the
      efficacy of CBT for various disorders is reviewed, including depression, anxiety
      disorders, personality disorders, eating disorders, substance abuse,
      schizophrenia, chronic pain, insomnia, and child/adolescent disorders. The
      relative efficacy of medication and CBT, or their combination, is also briefly
      considered. Future directions for research and treatment development are
      proposed. 

PMID- 26301763
TI  - Visions: Red-Tailed Hawk.

PMID- 26301762
TI  - Cognitive Behavioral and Psychodynamic Therapies: Points of Intersection and
      Divergence.
AB  - Cognitive behavioral therapy (CBT) and psychodynamic therapy (PDT) are two major
      paradigms in the mental health care field. The present article reviews broad
      similarities and differences between each tradition while acknowledging that such
      generalizations may overlook heterogeneity within each. However, it is believed
      that a comparison between CBT and PDT is beneficial in dispelling myths about
      each tradition, fostering dialogue, encouraging further scholarship and research.
      While not an exhaustive account, this article will examine how CBT and PDT differ
      in how they view several topics such as the unconscious, the therapeutic
      alliance, the role of homework, symptom reduction, and therapeutic heuristics.
      Commentary is also offered on how research may be more effectively and
      collaboratively integrated with clinical work from both traditions. Future
      directions for partnership and improving mental health treatments are also
      discussed. 

PMID- 26301765
TI  - Origin of 3.45 eV Emission Line and Yellow Luminescence Band in GaN Nanowires:
      Surface Microwire and Defect.
AB  - The physical origin of the strong emission line at 3.45 eV and broadening yellow
      luminescence (YL) band centered at 2.2 eV in GaN nanowire (NW) has been debated
      for many years. Here, we solve these two notable issues by using state-of-the-art
      first-principles calculations based on many-body perturbation theory combined
      with polarization-resolved experiments. We demonstrate that the ubiquitous
      surface "microwires" with amazing characteristics, i.e., the outgrowth
      nanocrystal along the NW side wall, are vital and offer a new perspective to
      provide insight into some puzzles in epitaxy materials. Furthermore, inversion of
      the top valence bands, in the decreasing order of crystal-field split-off hole
      (CH) and heavy/light hole, results in the optical transition polarized along the
      NW axis due to quantum confinement. The optical emission from bound excitons
      localized around the surface microwire to CH band is responsible for the 3.45 eV
      line with E?c polarization. Both gallium vacancy and carbon-related defects tend
      to assemble at the NW surface layer, determining the broadening YL band. 

PMID- 26301767
TI  - Perovskite photovoltaics: Hovering solar cells.

PMID- 26301766
TI  - Flexible high power-per-weight perovskite solar cells with chromium oxide-metal
      contacts for improved stability in air.
AB  - Photovoltaic technology requires light-absorbing materials that are highly
      efficient, lightweight, low cost and stable during operation. Organolead halide
      perovskites constitute a highly promising class of materials, but suffer limited
      stability under ambient conditions without heavy and costly encapsulation. Here,
      we report ultrathin (3 MUm), highly flexible perovskite solar cells with
      stabilized 12% efficiency and a power-per-weight as high as 23 W g(-1). To
      facilitate air-stable operation, we introduce a chromium oxide-chromium
      interlayer that effectively protects the metal top contacts from reactions with
      the perovskite. The use of a transparent polymer electrode treated with
      dimethylsulphoxide as the bottom layer allows the deposition-from solution at low
      temperature-of pinhole-free perovskite films at high yield on arbitrary
      substrates, including thin plastic foils. These ultra-lightweight solar cells are
      successfully used to power aviation models. Potential future applications include
      unmanned aerial vehicles-from airplanes to quadcopters and weather balloons-for
      environmental and industrial monitoring, rescue and emergency response, and
      tactical security applications. 

PMID- 26301769
TI  - Is Laparoscopic Bariatric Surgery a Safe Option in Extremely High-Risk Morbidly
      Obese Patients?
AB  - INTRODUCTION: Age, superobesity, and cardiopulmonary comorbidities define
      patients as high risk for bariatric surgery. We evaluated the outcomes following
      bariatric surgery in extremely high-risk patients. MATERIALS AND METHODS: Among
      3240 patients who underwent laparoscopic bariatric surgery at a single academic
      center from January 2006 through June 2012, extremely high-risk patients were
      identified using the following criteria: age >= 65 years, body mass index (BMI)
      >= 50 kg/m(2), and presence of at least two of six cardiopulmonary comorbidities,
      including hypertension, ischemic heart disease, congestive heart failure, chronic
      obstructive pulmonary disease, obstructive sleep apnea, and history of venous
      thromboembolism. Perioperative and intermediate-term outcomes were assessed.
      RESULTS: Forty-four extremely high-risk patients underwent laparoscopic Roux-en-Y
      gastric bypass (n = 23), adjustable gastric banding (n = 11), or sleeve
      gastrectomy (n = 10). Patients had a mean age of 67.9 +/- 2.7 years, a mean BMI
      of 54.8 +/- 5.5 kg/m(2), and a median of two (range, two to five) cardiopulmonary
      comorbidities. There was no conversion to laparotomy. Thirteen (29.5%) 30-day
      postoperative complications occurred; only six were major complications. Thirty
      day postoperative re-admission, re-operation, and mortality rates were 15.9%,
      2.3%, and 0%, respectively. Within a mean follow-up time of 24.0 +/- 18.4 months,
      late morbidity and mortality rates were 18.2% and 2.3%, respectively. The mean
      percentage total weight and excess weight losses after at least 1 year of follow
      up were 26.7 +/- 12.0% and 44.1 +/- 20.6%, respectively. CONCLUSIONS:
      Laparoscopic bariatric surgery is safe and can be performed with acceptable
      perioperative outcomes in extremely high-risk patients. Advanced age, BMI, and
      severe cardiopulmonary comorbidities should not exclude patients from
      consideration for bariatric surgery.

PMID- 26301770
TI  - Tattoolike Polyaniline Microparticle-Doped Gold Nanowire Patches as Highly
      Durable Wearable Sensors.
AB  - Wearable and highly sensitive strain sensors are essential components of
      electronic skin for future biomonitoring and human machine interfaces. Here we
      report a low-cost yet efficient strategy to dope polyaniline microparticles into
      gold nanowire (AuNW) films, leading to 10 times enhancement in conductivity and
      ~8 times improvement in sensitivity. Simultaneously, tattoolike wearable sensors
      could be fabricated simply by a direct "draw-on" strategy with a Chinese
      penbrush. The stretchability of the sensors could be enhanced from 99.7% to
      149.6% by designing curved tattoo with different radius of curvatures. We also
      demonstrated roller coating method to encapusulate AuNWs sensors, exhibiting
      excellent water resistibility and durability. Because of improved conductivity of
      our sensors, they can directly interface with existing wireless circuitry,
      allowing for fabrication of wireless flexion sensors for a human finger
      controlled robotic arm system. 

PMID- 26301768
TI  - Differential basal-to-apical accessibility of lamin A/C epitopes in the nuclear
      lamina regulated by changes in cytoskeletal tension.
AB  - Nuclear lamins play central roles at the intersection between cytoplasmic
      signalling and nuclear events. Here, we show that at least two N- and C-terminal
      lamin epitopes are not accessible at the basal side of the nuclear envelope under
      environmental conditions known to upregulate cell contractility. The
      conformational epitope on the Ig-domain of A-type lamins is more buried in the
      basal than apical nuclear envelope of human mesenchymal stem cells undergoing
      osteogenesis (but not adipogenesis), and in fibroblasts adhering to rigid (but
      not soft) polyacrylamide hydrogels. This structural polarization of the lamina is
      promoted by compressive forces, emerges during cell spreading, and requires lamin
      A/C multimerization, intact nucleoskeleton-cytoskeleton linkages (LINC), and
      apical-actin stress-fibre assembly. Notably, the identified Ig-epitope overlaps
      with emerin, DNA and histone binding sites, and comprises various laminopathy
      mutation sites. Our findings should help decipher how the physical properties of
      cellular microenvironments regulate nuclear events. 

PMID- 26301771
TI  - Adjunctive brexpiprazole 1 and 3 mg for patients with major depressive disorder
      following inadequate response to antidepressants: a phase 3, randomized, double
      blind study.
AB  - OBJECTIVE: To evaluate efficacy, safety, and tolerability of brexpiprazole
      adjunctive to antidepressant treatments (ADTs) in patients with major depressive
      disorder (as defined by DSM-IV-TR criteria) with inadequate response to ADTs.
      METHOD: Patients still depressed despite 1-3 prior ADTs followed by 8 weeks of
      prospective physician-determined, open-label ADT were randomized (1:1:1) to
      double-blind brexpiprazole 3 mg/d, brexpiprazole 1 mg/d, or placebo for 6 weeks.
      The primary efficacy end point was change in Montgomery-Asberg Depression Rating
      Scale (MADRS) total score from baseline to week 6. The key secondary efficacy end
      point was change in Sheehan Disability Scale mean score. The Hochberg procedure
      corrected for multiplicity. The efficacy population comprised all patients who
      had >= 1 dose of study drug with baseline and >= 1 postrandomization MADRS
      scores; the efficacy population per final protocol consisted of efficacy
      population patients meeting amended criteria for inadequate response throughout
      the 8-week prospective ADT. The study was conducted between June 2011 and
      September 2013. RESULTS: In the efficacy population per final protocol,
      brexpiprazole 3 mg (n = 213) showed a greater improvement in MADRS total score
      versus placebo (n = 203; -8.29 vs -6.33; P = .0079), whereas brexpiprazole 1 mg
      did not (n = 211; -7.64 vs -6.33; P = .0737). The brexpiprazole groups showed
      comparable improvement in SDS mean score versus placebo (least squares [LS] mean
      difference: [1 mg] -0.49, P = .0158; [3 mg] -0.48, P = .0191). The most frequent
      adverse events were akathisia (4.4%, 13.5%, 2.3%), headache (9.3%, 6.1%, 7.7%),
      and weight increase (6.6%, 5.7%, 0.9%) in brexpiprazole 1-mg, 3-mg, and placebo
      groups, respectively. Mean changes from baseline in Abnormal Involuntary Movement
      Scale (LS mean difference = 0.08, P = .0141) and Barnes Akathisia Rating Scale
      (LS mean difference = 0.17, P = .0001) total scores were significantly greater
      with brexpiprazole 3 mg versus placebo. CONCLUSIONS: Brexpiprazole 3 mg
      demonstrated efficacy versus placebo in the efficacy population per final
      protocol. Both doses of brexpiprazole were well tolerated. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT01360632.

PMID- 26301772
TI  - Seasonal and Particle Size-Dependent Variations of Hexabromocyclododecanes in
      Settled Dust: Implications for Sampling.
AB  - Particle size is a significant parameter which determines the environmental fate
      and the behavior of dust particles and, implicitly, the exposure risk of humans
      to particle-bound contaminants. Currently, the influence of dust particle size on
      the occurrence and seasonal variation of hexabromocyclododecanes (HBCDs) remains
      unclear. While HBCDs are now restricted by the Stockholm Convention, information
      regarding HBCD contamination in indoor dust in China is still limited. We
      analyzed composite dust samples from offices (n = 22), hotels (n = 3),
      kindergartens (n = 2), dormitories (n = 40), and main roads (n = 10). Each
      composite dust sample (one per type of microenvironment) was fractionated into 9
      fractions (F1-F9: 2000-900, 900-500, 500-400, 400-300, 300-200, 200-100, 100-74,
      74-50, and <50 MUm). Total HBCD concentrations ranged from 5.3 (road dust, F4) to
      2580 ng g(-1) (dormitory dust, F4) in the 45 size-segregated samples. The
      seasonality of HBCDs in indoor dust was investigated in 40 samples from two
      offices. A consistent seasonal trend of HBCD levels was evident with dust
      collected in the winter being more contaminated with HBCDs than dust from the
      summer. Particle size-selection strategy for dust analysis has been found to be
      influential on the HBCD concentrations, while overestimation or underestimation
      would occur with improper strategies. 

PMID- 26301773
TI  - Do I misconstrue? Sarcasm detection, emotion recognition, and theory of mind in
      Huntington disease.
AB  - OBJECTIVE: Emotion recognition has been widely studied in Huntington disease
      (HD), but only a few studies have investigated more complex social cognition and,
      when so, exclusively in manifest HD. The present study sought to investigate
      social-cognitive functions in a large, consecutive cohort of premanifest and
      manifest HD gene expansion carriers using tests assessing sarcasm detection,
      theory of mind (ToM), and emotion recognition. METHOD: Fifty manifest, 50
      premanifest HD gene expansion carriers, and 39 at risk gene expansion negative
      healthy controls were included. All participants were tested with sarcasm
      detection, ToM, and emotion recognition tasks. Between-group comparisons of test
      performances and correlation analyses of test performances and disease burden
      scores were made. RESULTS: Group comparisons showed significant differences in
      performances on the social-cognitive tests between manifest HD gene expansion
      carriers and healthy controls, but differences in performances between
      premanifest HD gene expansion carriers and healthy controls were not
      statistically significant. Correlation analysis showed that the worse test
      performances were associated with higher disease burden scores in all HD gene
      expansion carriers. CONCLUSION: Our findings support a theory of impaired social
      cognitive functions in the early stages of HD. Test performances decreased with
      increasing disease burden in all HD gene expansion carriers, suggesting that
      social-cognitive tests may be useful for tracking disease progression. Simple
      emotion recognition tasks are just as sensitive for measuring social-cognitive
      deficits as more complex measures, but knowledge of the quality of social
      cognitive impairments in HD can be of great importance to both patients and
      caregivers.

PMID- 26301775
TI  - When Microplastic Is Not Plastic: The Ingestion of Artificial Cellulose Fibers by
      Macrofauna Living in Seagrass Macrophytodetritus.
AB  - Dead leaves of the Neptune grass, Posidonia oceanica (L.) Delile, in the
      Mediterranean coastal zone, are colonized by an abundant "detritivorous"
      invertebrate community that is heavily predated by fishes. This community was
      sampled in August 2011, November 2011, and March 2012 at two different sites in
      the Calvi Bay (Corsica). Ingested artificial fibers (AFs) of various sizes and
      colors were found in 27.6% of the digestive tracts of the nine dominant species
      regardless of their trophic level or taxon. No seasonal, spatial, size, or
      species-specific significant differences were revealed; suggesting that
      invertebrates ingest AFs at constant rates. Results showed that, in the gut
      contents of invertebrates, varying by trophic level, and across trophic levels,
      the overall ingestion of AFs was low (approximately 1 fiber per organism). Raman
      spectroscopy revealed that the ingested AFs were composed of viscose, an
      artificial, cellulose-based polymer. Most of these AFs also appeared to have been
      colored by industrial dyes. Two dyes were identified: Direct Blue 22 and Direct
      Red 28. The latter is known for being carcinogenic for vertebrates, potentially
      causing environmental problems for the P. oceanica litter community. Techniques
      such as Raman spectroscopy are necessary to investigate the particles
      composition, instead of relying on fragment size or color to identify the
      particles ingested by animals. 

PMID- 26301774
TI  - Neurocognitive performance in unmedicated patients with hoarding disorder.
AB  - OBJECTIVE: Hoarding disorder (HD) is an often incapacitating psychiatric illness
      associated with a wide range of neurocognitive abnormalities. Some prior
      neuropsychological studies have found executive dysfunction in HD, but no clear
      pattern has emerged. One potential reason for discrepant results in previous
      studies might be the inclusion of patients on psychotropic and other medications
      that can affect neurocognitive performance. Therefore, we examined neurocognitive
      functioning in medication-free HD patients. We also added a novel investigation
      of implicit learning, which has been found to be abnormal in obsessive-compulsive
      disorder (OCD) and related disorders. METHOD: Twenty-six participants meeting the
      Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5; American
      Psychiatric Association, 2013) diagnostic criteria for HD and 23 normal controls
      were administered a battery of neuropsychological tests and symptom rating
      scales. All participants were free of psychotropic medications for at least 6
      weeks prior to the study. RESULTS: HD participants showed no significant
      differences from normal controls on measures of verbal memory, attention, or
      executive functioning, including response inhibition, planning, organization, and
      decision making. However, HD participants demonstrated a trend toward less
      implicit learning and greater use of explicit learning strategies during
      perceptual categorization compared to normal controls. HD participants who used
      an implicit strategy performed significantly worse than controls who used an
      implicit strategy. Hoarding symptom severity was not associated with
      neurocognitive performance. CONCLUSIONS: HD patients may have a tendency to use
      explicit rather than implicit learning strategies for perceptual categorization
      but perform as well as normal controls on many other neurocognitive measures.
      Future studies should assess unmedicated participants and examine test
      strategies, not just outcomes.

PMID- 26301776
TI  - Risk ON/Risk OFF: Risk-Taking Varies with Subjectively Preferred and Disliked
      Music.
AB  - In this paper we conduct a within-subjects experiment in which teenagers go over
      256 gambles with real money gains and losses. For each risky gamble they choose
      whether to participate in it, or pass. Prior to this main experiment subjects
      identify specific songs belonging to their favorite musical genre, as well as
      songs representing a style they dislike. In the main experiment we vary the music
      playing in the background, so that each subject hears some of their favorite
      music, and some disliked music, alternating in blocks of 16 gambles. We find that
      favorite music increases risk-taking ('risk on'), and disliked music suppresses
      risk-taking ('risk off'), compared to a baseline of no music. Literature in
      psychology proposes several mechanisms by which mood affects risk-taking, but
      none of them fully explain the results in our setting. The results are, however,
      consistent with the economics notion of preference complementarity, extended to
      the domain of risk preference. The preference structure implied by our results is
      more complex than previously thought, yet realistic, and consistent with recent
      theoretical models. More generally, this mechanism offers a potential explanation
      to why risk-taking is known to change over time and across contexts. 

PMID- 26301777
TI  - Maleimide Glycidyl Ether: A Bifunctional Monomer for Orthogonal Cationic and
      Radical Polymerizations.
AB  - A novel bifunctional monomer, namely maleimide glycidyl ether (MalGE), prepared
      in a four-step reaction sequence is introduced. This monomer allows for selective
      (co)polymerization of the epoxide group via cationic ring-opening polymerization,
      preserving the maleimide functionality. On the other hand, the maleimide
      functionality can be copolymerized via radical techniques, preserving the epoxide
      moiety. Cationic ring-opening multibranching copolymerization of MalGE with
      glycidol was performed, and a MalGE content of up to 24 mol% could be
      incorporated into the hyperbranched polymer backbone (Mn = 1000-3000 g mol(-1)).
      Preservation of the maleimide functionality during cationic copolymerization was
      verified via NMR spectroscopy. Subsequently, the maleimide moiety was radically
      crosslinked to generate hydrogels and additionally employed to perform Diels
      Alder (DA) "click" reactions with (functional) dienes after the polymerization
      process. Radical copolymerization of MalGE with styrene (Mn = 5000-9000 g mol(
      1)) enabled the synthesis of a styrene copolymer with epoxide functionalities
      that are useful for versatile crosslinking and grafting reactions.

PMID- 26301779
TI  - No evidence for alphaGal epitope transfer from media containing FCS onto human
      endothelial cells in culture.
AB  - BACKGROUND: Current clinical applications of cell therapies and tissue engineered
      (TE) constructs aim to generate non-immunogenic cells in the best-case scenario
      of autologous origin. As the cells are cultured, it is theoretically possible
      that immunoreactive molecules present in xenogenic cell culture media components,
      such as fetal calf serum (FCS), are transmitted in the culturing process. This
      problem has propelled the search for xeno-free culture media; however, in vitro
      culturing of many cell types, especially TE constructs which consist of several
      cell types, still relies to a great extent on FCS. In this study, we investigated
      the degree to which xenoantigens are transmitted to human endothelial cells (EC)
      cultured in medium containing FCS. METHODS: Human EC were isolated from pulmonary
      artery fragments and atrial appendage tissue samples by enzymatic digestion
      followed by magnetic-activated cell separation (MACS) utilizing CD31 antibodies.
      The cells were cultured in EGM-2 medium containing 10% FCS for several passages.
      Griffonia Simplicifolia Lectin I - Isolectin B4 (GSL I-B4) was used to detect
      cell surface-bound alphaGal epitopes either microscopically or flow
      cytometrically. Antibody binding to cells exposed to human sera prepared from
      healthy blood donors was investigated to detect surface-located xenoantigens. An
      antibody-dependent cytotoxicity assay was conducted with heat-inactivated human
      serum supplemented with rabbit complement and analyzed by flow cytometry after
      staining for living and dead cells (LIVE/DEAD assay kit). In all experiments,
      cells cultured in EGM-2 supplemented with 10% human serum (HS) served as
      controls. RESULTS: Human EC were isolated and cultured successfully for >=6
      passages. GSL I-B4 staining showed no difference between human EC cultured in FCS
      and in HS. In contrast to porcine EC which showed strong staining with GSL I-B4
      and binding of preformed human serum antibodies, human EC cultured in FCS media
      did not bind human antibodies from high titer anti-alphaGal and anti-Neu5GC
      antibody serum. Along these lines, the antibody-dependent cytotoxicity assay
      showed that human EC cultures independent of FCS or HS usage were not affected,
      whereas about 40% of porcine EC did not survive. CONCLUSION: Despite culturing
      cells in an environment containing xenoantigens, we were unable to demonstrate
      the translocation of xenogenic epitopes onto the surface of human EC or find an
      increased sensitivity in preformed human xenoantibody-dependent complement
      activity. Therefore, our results suggest that the use of human cells for TE or
      cell therapy grown in cell culture systems complemented with FCS does not
      necessarily lead to an acute rejection reaction upon implantation.

PMID- 26301778
TI  - Changes in Diffusion Kurtosis Imaging and Magnetic Resonance Spectroscopy in a
      Direct Cranial Blast Traumatic Brain Injury (dc-bTBI) Model.
AB  - Explosive blast-related injuries are one of the hallmark injuries of veterans
      returning from recent wars, but the effects of a blast overpressure on the brain
      are poorly understood. In this study, we used in vivo diffusion kurtosis imaging
      (DKI) and proton magnetic resonance spectroscopy (MRS) to investigate tissue
      microstructure and metabolic changes in a novel, direct cranial blast traumatic
      brain injury (dc-bTBI) rat model. Imaging was performed on rats before injury and
      1, 7, 14 and 28 days after blast exposure (~517 kPa peak overpressure to the
      dorsum of the head). No brain parenchyma abnormalities were visible on
      conventional T2-weighted MRI, but microstructural and metabolic changes were
      observed with DKI and proton MRS, respectively. Increased mean kurtosis, which
      peaked at 21 days post injury, was observed in the hippocampus and the internal
      capsule. Concomitant increases in myo-Inositol (Ins) and Taurine (Tau) were also
      observed in the hippocampus, while early changes at 1 day in the Glutamine (Gln)
      were observed in the internal capsule, all indicating glial abnormality in these
      regions. Neurofunctional testing on a separate but similarly treated group of
      rats showed early disturbances in vestibulomotor functions (days 1-14), which
      were associated with imaging changes in the internal capsule. Delayed impairments
      in spatial memory and in rapid learning, as assessed by Morris Water Maze
      paradigms (days 14-19), were associated with delayed changes in the hippocampus.
      Significant microglial activation and neurodegeneration were observed at 28 days
      in the hippocampus. Overall, our findings indicate delayed neurofunctional and
      pathological abnormalities following dc-bTBI that are silent on conventional T2
      weighted imaging, but are detectable using DKI and proton MRS. 

PMID- 26301780
TI  - An ultrastructural study on corkscrew hairs and cigarette-ash-shaped hairs
      observed by dermoscopy of tinea capitis.
AB  - This study was aimed to explain the formation mechanisms of corkscrew hairs and
      cigarette-ash-shaped hairs observed by dermoscopy of tinea capitis. In the
      present work, the ultrastructure of the involved hairs collected from a girl with
      tinea capitis caused by Trichophyton violaceum was observed by scanning electron
      microscope (SEM) and transmission electron microscope (TEM). SEM observation of
      the corkscrew hair revealed bent hair shaft and asymmetrically disrupted cuticle
      layer. TEM findings demonstrated the hair shaft became weak. The corkscrew hairs
      closely covered by scales on the scalp were observed under dermoscopy. We
      speculate that the formation of corkscrew hairs is a result of a combination of
      internal damage due to hair degradation by T. violaceum and external resistance
      due to scales covering the hair. SEM observation of the cigarette-ash-shaped hair
      revealed irregularly disrupted and incompact end, which might represent the stump
      of the broken corkscrew hair after treatment.

PMID- 26301781
TI  - Over-Reporting in Handwashing Self-Reports: Potential Explanatory Factors and
      Alternative Measurements.
AB  - Handwashing interventions are a priority in development and emergency aid
      programs. Evaluation of these interventions is essential to assess the
      effectiveness of programs; however, measuring handwashing is quite difficult.
      Although observations are considered valid, they are time-consuming and cost
      ineffective; self-reports are highly efficient but considered invalid because
      desirable behaviour tends to be over-reported. Socially desirable responding has
      been claimed to be the main cause of inflated self-reports, but its underlying
      factors and mechanisms are understudied. The present study investigated socially
      desirable responding and additional potential explanatory factors for over
      reported handwashing to identify indications for measures which mitigate over
      reporting. Additionally, a script-based covert recall, an alternative interview
      question intended to mitigate recall errors and socially desirable responding,
      was developed and tested. Cross-sectional data collection was conducted in the
      Borena Zone, Ethiopia, through 2.5-hour observations and 1-hour interviews with
      the primary caregivers in households. A total sample of N = 554 was surveyed.
      Data were analysed with correlation and multiple regression analyses and
      dependent t-tests. Over-reporting of handwashing was associated with factors
      assumed to be involved in (1) socially desirable responding, (2) encoding and
      recall of information, and (3) dissonance processes. The latter two factor groups
      explained over-reported handwashing beyond socially desirable responding. The
      alternative interview question--script-based covert recall--reduced over
      reporting compared to conventional self-reports. Although the difficulties
      involved in measuring handwashing by self-reports and observations are widely
      known, the present study is the first to investigate the factors which explain
      over-reporting of handwashing. This research contributes to the limited evidence
      base on a highly important subject: how to evaluate handwashing interventions
      efficiently and accurately.

PMID- 26301783
TI  - Correction: Do Payments Pay Off? Evidence from Participation in Costa Rica's PES
      Program.

PMID- 26301782
TI  - The Lumbar Lordosis in Males and Females, Revisited.
AB  - BACKGROUND: Whether differences exist in male and female lumbar lordosis has been
      debated by researchers who are divided as to the nature of variations in the
      spinal curve, their origin, reasoning, and implications from a morphological,
      functional and evolutionary perspective. Evaluation of the spinal curvature is
      constructive in understanding the evolution of the spine, as well as its
      pathology, planning of surgical procedures, monitoring its progression and
      treatment of spinal deformities. The aim of the current study was to revisit the
      nature of lumbar curve in males and females. METHODS: Our new automated method
      uses CT imaging of the spine to measure lumbar curvature in males and females.
      The curves extracted from 158 individuals were based on the spinal canal, thus
      avoiding traditional pitfalls of using bone features for curve estimation. The
      model analysis was carried out on the entire curve, whereby both local and global
      descriptors were examined in a single framework. Six parameters were calculated:
      segment length, curve length, curvedness, lordosis peak location, lordosis
      cranial peak height, and lordosis caudal peak height. PRINCIPAL FINDINGS:
      Compared to males, the female spine manifested a statistically significant
      greater curvature, a caudally located lordotic peak, and greater cranial peak
      height. As caudal peak height is similar for males and females, the illusion of
      deeper lordosis among females is due partially to the fact that the upper part of
      the female lumbar curve is positioned more dorsally (more backwardly inclined).
      CONCLUSIONS: Males and females manifest different lumbar curve shape, yet similar
      amount of inward curving (lordosis). The morphological characteristics of the
      female spine were probably developed to reduce stress on the vertebral elements
      during pregnancy and nursing.

PMID- 26301784
TI  - Context is Everything: An Investigation of Responsibility Beliefs and
      Interpretations and the Relationship with Obsessive-Compulsive Symptomatology
      across the Perinatal Period.
AB  - BACKGROUND: The cognitive-behavioural model of perinatal OCD suggests the role of
      increased sense of responsibility during the perinatal period in the development
      and maintenance of obsessive-compulsive symptoms. However, the idiosyncratic
      nature of responsibility attitudes and interpretations of intrusions is not fully
      understood. AIMS: To investigate how responsibility interpretations regarding
      intrusions vary across the perinatal period and how this relates to obsessive
      compulsive symptomatology. METHOD: 94 women (26 antenatal, 35 postpartum and 33
      non-childbearing controls) completed measures of responsibility attitudes and
      interpretations regarding specific intrusions (either general or baby-related),
      as well as obsessive-compulsive symptomatology, anxiety and depression. RESULTS:
      Postpartum ratings of responsibility interpretations regarding baby-related
      intrusions were significantly higher than: i) postpartum ratings of
      responsibility interpretations regarding non-baby intrusions; and ii) control
      group responsibility interpretations. The groups were not significantly different
      regarding general responsibility ratings. Ratings of baby-related responsibility
      interpretations predicted variance in obsessive-compulsive symptomatology.
      CONCLUSION: The postpartum group showed significant differences in responsibility
      interpretations regarding baby-related intrusions. These responsibility
      interpretations were shown to predict obsessive-compulsive symptomatology.

PMID- 26301785
TI  - In vivo free-breathing DTI and IVIM of the whole human heart using a real-time
      slice-followed SE-EPI navigator-based sequence: A reproducibility study in
      healthy volunteers.
AB  - PURPOSE: In this study, we proposed an efficient free-breathing strategy for
      rapid and improved cardiac diffusion-weighted imaging (DWI) acquisition using a
      single-shot spin-echo echo planar imaging (SE-EPI) sequence. METHODS: A real-time
      slice-following technique during free-breathing was combined with a sliding
      acquisition-window strategy prior Principal Component Analysis temporal Maximum
      Intensity Projection (PCAtMIP) postprocessing of in-plane co-registered diffusion
      weighted images. This methodology was applied to 10 volunteers to quantify the
      performance of the motion correction technique and the reproducibility of
      diffusion parameters. RESULTS: The slice-following technique offers a powerful
      head-foot respiratory motion management solution for SE-EPI cDWI with the
      advantage of a 100% duty cycle scanning efficiency. The level of co-registration
      was further improved using nonrigid motion corrections and was evaluated with a
      co-registration index. Vascular fraction f and the diffusion coefficients D and
      D* were determined to be 0.122 +/- 0.013, 1.41 +/- 0.09 * 10(-3) mm(2) /s and
      43.6 +/- 9.2 * 10(-3) mm(2) /s, respectively. From the multidirectional dataset,
      the measured mean diffusivity was 1.72 +/- 0.09 * 10(-3) mm(2) /s and the
      fractional anisotropy was 0.36 +/- 0.02. CONCLUSION: The slice-following DWI SE
      EPI sequence is a promising solution for clinical implementation, offering a
      robust improved workflow for further evaluation of DWI in cardiology. Magn Reson
      Med 76:70-82, 2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 26301786
TI  - Molecular insight and pharmacological approaches targeting mitochondrial dynamics
      in skeletal muscle during obesity.
AB  - Obesity-associated insulin resistance is the major characteristic of the early
      stage of metabolic syndrome. A decline in mitochondrial function plays a role in
      the development of insulin resistance in obesity and type 2 diabetes.
      Accumulating data reveal that mitochondrial dynamics, the balance between
      mitochondrial fusion and fission, are an important factor in the maintenance of
      mitochondrial function. Thus, the mechanisms underlying the regulation of
      mitochondrial dynamics in obesity deserve further investigation. This review
      describes an overview of mitochondrial fusion and fission machineries, and
      discusses the mechanistic and functional aspects of mitochondrial dynamics, with
      a focus on skeletal muscle in obesity. Finally, we discuss current
      pharmacological approaches of targeting mitochondrial dynamics. Elucidating the
      role of mitochondrial dynamics in skeletal muscle afflicted by obesity may
      provide not only important clues in understanding muscle insulin resistance, but
      also new therapeutic targets. 

PMID- 26301787
TI  - Fistulation into the Pubic Symphysis after Treatment of Prostate Cancer: An
      Important and Surgically Correctable Complication.
AB  - PURPOSE: Chronic pubic pain after the treatment of prostate cancer is often
      attributed to osteitis pubis. We have become aware of another complication,
      namely fistulation into the pubic symphysis, which is more serious and more
      common than previously thought. MATERIALS AND METHODS: A total of 16 patients
      were treated for urosymphyseal fistulas after the treatment of prostate cancer
      between January 2011 and April 2014. Clinical presentation was characterized by
      chronic, debilitating pubic/pelvic/groin pain in all patients. Diagnosis was
      confirmed by magnetic resonance imaging. Conservative management was successful
      in only 1 patient. The remaining patients were treated surgically with excision
      of the fistulous track and involved symphyseal bone and omentoplasty, followed by
      reconstruction when feasible. RESULTS: All 16 patients had had radiotherapy as
      primary treatment (8) or after prostatectomy (8). There were 5 patients (31.3%)
      who underwent various combinations of brachytherapy, external beam radiotherapy
      and cryotherapy. Bladder neck contractures developed in 13 patients (81.3%),
      whose treatment (endoscopic or open reconstruction) resulted in urinary leak
      leading to urosymphyseal fistulas. Reconstruction was possible in 7 of 15
      patients (46.7%) with salvage radical prostatectomy and substitution/augmentation
      cystoplasty. The other 8 patients (53.3%) underwent cystectomy and ileal conduit
      diversion. All patients experienced resolution of symptoms, most significantly
      the almost immediate resolution of pain. CONCLUSIONS: A high index of suspicion
      must be maintained in irradiated patients presenting with symptoms suggestive of
      urosymphyseal fistulas, especially after having undergone treatment of bladder
      neck contractures or prostatic urethral stenoses. Although extensive, surgery for
      urosymphyseal fistulas, with a high risk of morbidity and mortality and a
      protracted recovery, leads to immediate and dramatic improvement in symptoms.

PMID- 26301788
TI  - Use of the Acoustic Shadow Width to Determine Kidney Stone Size with Ultrasound.
AB  - PURPOSE: Ultrasound is known to overestimate kidney stone size. We explored
      measuring the acoustic shadow behind kidney stones combined with different
      ultrasound imaging modalities to improve stone sizing accuracy. MATERIALS AND
      METHODS: A total of 45 calcium oxalate monohydrate stones were imaged in vitro at
      3 different depths with the 3 different ultrasound imaging modalities of
      conventional ray line, spatial compound and harmonic imaging. The width of the
      stone and the width of the acoustic shadow were measured by 4 operators blinded
      to the true size of the stone. RESULTS: Average error between the measured and
      true stone width was 1.4 +/- 0.8 mm, 1.7 +/- 0.9 mm, 0.9 +/- 0.8 mm for ray line,
      spatial compound and harmonic imaging, respectively. Average error between the
      shadow width and true stone width was 0.2 +/- 0.7 mm, 0.4 +/- 0.7 mm and 0.0 +/-
      0.8 mm for ray line, spatial compound and harmonic imaging, respectively. Sizing
      error based on the stone width worsened with greater depth (p <0.001) while the
      sizing error based on the shadow width was independent of depth. CONCLUSIONS:
      Shadow width was a more accurate measure of true stone size than a direct
      measurement of the stone in the ultrasound image (p <0.0001). The ultrasound
      imaging modality also impacted the measurement accuracy. All methods performed
      similarly for shadow size while harmonic imaging was the most accurate stone size
      modality. Overall 78% of the shadow sizes were accurate to within 1 mm, which is
      similar to the resolution obtained with clinical computerized tomography.

PMID- 26301789
TI  - Limitation of syntrophic coculture growth by the acetogen.
AB  - The syntrophic cooperation between hydrogen-producing acetogens and
      hydrogenotrophic methanogens relies on a critical balance between both partners.
      A recent study, provided several indications for the dependence of the biomass
      specific growth rate of a methanogenic coculture on the acetogen. Nevertheless,
      final experimental proof was lacking since biomass-specific rates were obtained
      from a descriptive model, and not from direct measurement of individual biomass
      concentrations. In this study, a recently developed quantitative PCR approach was
      used to measure the individual biomass concentrations in the coculture of
      Desulfovibrio sp. G11 and Methanospirillum hungatei JF1 on lactate, formate or
      both. The model-derived growth yields and biomass-specific rates were
      successfully validated. Experimental findings identified the acetogen as the
      growth-limiting partner in the coculture on lactate. While the acetogen was
      operating at its maximum biomass-specific lactate consumption rate, the
      hydrogenotrophic methanogen showed a significant overcapacity. Furthermore, this
      study provides experimental evidence for different growth strategies followed by
      the syntrophic partners in order to maintain a common biomass-specific growth
      rate. During syntrophic lactate conversion, the biomass-specific electron
      transfer rate of Methanospirillum hungatei JF1 was three-fold higher compared to
      Desulfovibrio sp. G11. This is to compensate for the lower methanogenic biomass
      yield per electron-mole of substrate, which is dictated by the thermodynamics of
      the underlying reaction.

PMID- 26301790
TI  - Nutritional support in children and young people with cancer undergoing
      chemotherapy.
AB  - BACKGROUND: It is well documented that malnutrition is a common complication of
      paediatric malignancy and its treatment. Malnutrition can often be a consequence
      of cancer itself or a result of chemotherapy. Nutritional support aims to reverse
      malnutrition seen at diagnosis, prevent malnutrition associated with treatment
      and promote weight gain and growth. The most effective and safe forms of
      nutritional support in children and young people with cancer are not known.
      OBJECTIVES: To determine the effects of any form of parenteral (PN) or enteral
      (EN) nutritional support, excluding vitamin supplementation and micronutrient
      supplementation, in children and young people with cancer undergoing chemotherapy
      and to determine the effect of the nutritional content of PN and EN. This is an
      update of a previous Cochrane review. SEARCH METHODS: We searched the following
      databases for the initial review: CENTRAL (The Cochrane Library, Issue 2, 2009),
      MEDLINE (1950 to 2006), EMBASE (1974 to 2006), CINAHL (1982 to 2006), the
      National Research Register (2007) and Dissertations & Theses (2007). Experts in
      the field were also contacted for information on relevant trials. For this
      update, we searched the same electronic databases from 2006 to September 2013. We
      also scrutinised the reference lists of included articles to identify additional
      trials. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials
      comparing any form of nutritional support with another, or control, in children
      or young people with cancer undergoing chemotherapy. DATA COLLECTION AND
      ANALYSIS: Two authors independently selected trials. At least two authors
      independently assessed quality and extracted data. We contacted trialists for
      missing information. MAIN RESULTS: The current review included the eight trials
      from the initial review and six new trials which randomised 595 participants (<
      21 years of age) with leukaemias or solid tumours undergoing chemotherapy. The
      trials were all of low quality with the exception of two of the trials looking at
      glutamine supplementation. One small trial found that compared to EN, PN
      significantly increased weight (mean difference (MD) 4.12, 95% CI 1.91 to 6.33),
      serum albumin levels (MD 0.70, 95% CI 0.14 to 1.26), calorie intake (MD 22.00,
      95% CI 5.12 to 38.88) and protein intake (MD 0.80, 95% CI 0.45 to 1.15). One
      trial comparing peripheral PN and EN with central PN found that mean daily weight
      gain (MD -27.00, 95% CI -43.32 to -10.68) and energy intake (MD -15.00, 95% CI 
      26.81 to -3.19) were significantly less for the peripheral PN and EN group,
      whereas mean change in serum albumin was significantly greater for that group (MD
      0.47, 95% CI 0.13 to 0.81, P = 0.008). Another trial with few participants found
      an increase in mean energy intake (% recommended daily amount) in children fed an
      energy dense feed compared to a standard calorie feed (MD +28%, 95% CI 17% to
      39%). Three studies looked at glutamine supplementation. The evidence suggesting
      that glutamine reduces severity of mucositis was not statistically significant in
      two studies (RR 0.64, 95% CI 0.19 to 2.2 and RR 0.85, 95% CI 0.66 to 1.1) and
      differences in reduction of infection rates were also not significant in two
      studies (RR 1.0, 95% CI 0.72 to 1.4 and RR 0.98, 95% CI 0.63 to 1.51). Only one
      study compared olive oil based PN to standard lipid containing PN. Despite
      similar calorie contents in both feeds, the standard lipid formula lead to
      greater weight gain (MD -0.34 z-scores, 95% CI -0.68 to 0.00). A single study
      compared standard EN with fructooligosaccharide containing EN. There was no
      difference in weight gain between groups (mean difference -0.12, 95% CI -0.57 to
      0.33), with adverse effects (nausea) occurring equally between the groups (RR
      0.92, 95% CI 0.48 to 1.74). AUTHORS' CONCLUSIONS: There is limited evidence from
      individual trials to suggest that PN is more effective than EN in well-nourished
      children and young people with cancer undergoing chemotherapy. The evidence for
      other methods of nutritional support remains unclear. Limited evidence suggests
      an energy dense feed increases mean daily energy intake and has a positive effect
      on weight gain. Evidence suggesting glutamine supplementation reduces incidence
      and severity of mucositis, infection rates and length of hospital stay is not
      statistically significant. Further research, incorporating larger sample sizes
      and rigorous methodology utilising valid and reliable outcome measures, is
      essential.

PMID- 26301792
TI  - An Injudicious Request--Performing a Test That Is Not Indicated.

PMID- 26301791
TI  - An Analysis of Rescue Medication Utilization from a 3-Month, Randomized, Double
      Blind, Placebo-Controlled Study in Patients with Chronic Low Back Pain Treated
      with Single-Entity, Twice-Daily, Extended-Release Hydrocodone.
AB  - OBJECTIVE: To evaluate the durability of pain relief provided by a new
      formulation of single-entity, hydrocodone extended-release (ER) (Zohydro((r)) ER)
      throughout the 12-hour dosing interval by examining patterns of rescue medication
      use. DESIGN: Phase 3, enriched enrollment, randomized withdrawal study with an
      open-label, conversion/titration phase (<=6 weeks) followed by a placebo
      controlled, double-blind treatment phase (12 weeks). SETTING: Fifty-seven study
      sites in the United States enrolled patients. SUBJECTS: One hundred and fifty-one
      opioid-experienced subjects with moderate to severe chronic low back pain who
      were treated with hydrocodone ER once every 12 hours. METHODS: Post hoc analysis
      of rescue medication use by frequency and distribution of use following the
      morning and evening dose of hydrocodone ER. RESULTS: No rescue medication was
      used following the morning or evening dose of hydrocodone ER during 36.0% and
      76.7% of the dosing days, respectively. Time distribution of rescue medication
      use showed that 79.3% of all rescue medication doses were administered following
      the morning dose, with the highest rate of usage (46.2%) occurring 4-8 hours
      postdose, followed by 18.7% and 14.4% usage 0-4 and 8-12 hours postdose,
      respectively. Examination of the three 4-hour intervals following the evening
      dose of hydrocodone ER revealed similar minimal rescue medication use (5.6-8.2%).
      CONCLUSIONS: End-of-dose failure was not observed based on the use of rescue
      medication after administration of single-entity, twice daily, hydrocodone ER
      capsules (Zohydro ER).

PMID- 26301793
TI  - Idiopathic Bilateral External Jugular Vein Thrombosis.
AB  - BACKGROUND: Vein thrombosis is mainly determined by 3 factors, which constitute a
      triad called Virchow's triad: hypercoagulability, stasis, and endothelial injury.
      Venous thrombosis commonly occurs in the lower extremities since most of the
      blood resides there and flows against gravity. The veins of the lower extremities
      are dependent on intact valves and fully functional leg muscles. However, in case
      of valvular incompetency or muscular weakness, thrombosis and blood stasis will
      occur as a result. In contrast, the veins of the neck, specially the jugulars,
      have distensible walls which allow flexibility during respiration. In addition,
      the blood directly flows downward towards the heart. Nevertheless, many case
      reports mentioned the thrombosis of internal jugular veins and external jugular
      veins with identified risk factors. Jugular vein thrombosis has previously been
      associated in the literature with a variety of medical conditions, including
      malignancy. CASE REPORT: This report is of a case of idiopathic bilateral
      external jugular vein thrombosis in a 21 year-old male construction worker of
      Southeast Asian origin with no previous medical history who presented with
      bilateral facial puffiness of gradual onset over 1 month. Doppler ultrasound and
      computed tomography were used in the diagnosis. Further work-up showed no
      evidence of infection or neoplasia. The patient was eventually discharged on
      warfarin. The patient was assessed after 6 months and his symptoms had resolved
      completely. CONCLUSIONS: Bilateral idiopathic external jugular veins thrombosis
      is extremely rare and can be an indicator of early malignancy or hidden
      infection. While previous reports in the literature have associated jugular vein
      thrombosis with malignancy, the present case shows that external jugular vein
      thrombosis can also be found in persons without malignancy.

PMID- 26301794
TI  - Physically scarce (vs. enriched) environments decrease the ability to tell lies
      successfully.
AB  - The successful detection of deception is of critical importance to adaptive
      social relationships and organizations, and perhaps even national security.
      However, research in forensic, legal, and social psychology demonstrates that
      people are generally very successful deceivers. The goal of the current research
      was to test an intervention with the potential to decrease the likelihood of
      successful deception. We applied findings in the architectural, engineering, and
      environmental sciences that has demonstrated that enriched environments (vs.
      scarce ones) promote the experience of comfort, positive emotion, feelings of
      power and control, and increase productivity. We hypothesized that sparse,
      impoverished, scarcely endowed environments (vs. enriched ones) would decrease
      the ability to lie successfully by making liars feel uncomfortable and powerless.
      Study 1 examined archival footage of an international sample of criminal suspects
      (N = 59), including innocent relatives (n = 33) and convicted murderers (n = 26)
      emotionally pleading to the public for the return of a missing person. Liars in
      scarce environments (vs. enriched) were significantly more likely to reveal their
      lies through behavioral cues to deception. Study 2 (N = 79) demonstrated that the
      discomfort and subsequent powerlessness caused by scarce (vs. enriched)
      environments lead people to reveal behavioral cues to deception. Liars in scarce
      environments also experienced greater neuroendocrine stress reactivity and were
      more accurately detected by a sample of 66 naive observers (Study 3). Taken
      together, data suggest that scarce environments increase difficulty, and decrease
      success, of deception. Further, we make available videotaped stimuli of Study 2
      liars and truth-tellers.

PMID- 26301795
TI  - Knowledge does not protect against illusory truth.
AB  - In daily life, we frequently encounter false claims in the form of consumer
      advertisements, political propaganda, and rumors. Repetition may be one way that
      insidious misconceptions, such as the belief that vitamin C prevents the common
      cold, enter our knowledge base. Research on the illusory truth effect
      demonstrates that repeated statements are easier to process, and subsequently
      perceived to be more truthful, than new statements. The prevailing assumption in
      the literature has been that knowledge constrains this effect (i.e., repeating
      the statement "The Atlantic Ocean is the largest ocean on Earth" will not make
      you believe it). We tested this assumption using both normed estimates of
      knowledge and individuals' demonstrated knowledge on a postexperimental knowledge
      check (Experiment 1). Contrary to prior suppositions, illusory truth effects
      occurred even when participants knew better. Multinomial modeling demonstrated
      that participants sometimes rely on fluency even if knowledge is also available
      to them (Experiment 2). Thus, participants demonstrated knowledge neglect, or the
      failure to rely on stored knowledge, in the face of fluent processing
      experiences.

PMID- 26301796
TI  - Probing intrinsic anisotropies of fluorescence: Mueller matrix approach.
AB  - We demonstrate that information on "intrinsic" anisotropies of fluorescence
      originating from preferential orientation/organization of fluorophore molecules
      can be probed using a Mueller matrix of fluorescence. For this purpose, we have
      developed a simplified model to decouple and separately quantify the
      depolarization property and the intrinsic anisotropy properties of fluorescence
      from the experimentally measured fluorescence Mueller matrix. Unlike the
      traditionally defined fluorescence anisotropy parameter, the Mueller matrix
      derived fluorescence polarization metrics, namely, fluorescence diattenuation and
      polarizance parameters, exclusively deal with the intrinsic anisotropies of
      fluorescence. The utility of these newly derived fluorescence polarimetry
      parameters is demonstrated on model systems exhibiting multiple polarimetry
      effects, and an interesting example is illustrated on biomedically important
      fluorophores, collagen.

PMID- 26301797
TI  - Highly Ordered Mesoporous Cobalt-Containing Oxides: Structure, Catalytic
      Properties, and Active Sites in Oxidation of Carbon Monoxide.
AB  - Co3O4 with a spinel structure is a very active oxide catalyst for the oxidation
      of CO. In such catalysts, octahedrally coordinated Co(3+) is considered to be the
      active site, while tetrahedrally coordinated Co(2+) is assumed to be basically
      inactive. In this study, a highly ordered mesoporous CoO has been prepared by H2
      reduction of nanocast Co3O4 at low temperature (250  degrees C). The as-prepared
      CoO material, which has a rock-salt structure with a single Co(2+) octahedrally
      coordinated by lattice oxygen in Fm3m symmetry, exhibited unexpectedly high
      activity for CO oxidation. Careful investigation of the catalytic behavior of
      mesoporous CoO catalyst led to the conclusion that the oxidation of surface
      Co(2+) to Co(3+) causes the high activity. Other mesoporous spinels (CuCo2O4,
      CoCr2O4, and CoFe2O4) with different Co species substituted with non/low-active
      metal ions were also synthesized to investigate the catalytically active site of
      cobalt-based catalysts. The results show that not only is the octahedrally
      coordinated Co(3+) highly active but also the octahedrally coordinated Co(2+)
      species in CoFe2O4 with an inverse spinel structure shows some activity. These
      results suggest that the octahedrally coordinated Co(2+) species is easily
      oxidized and shows high catalytic activity for CO oxidation. 

PMID- 26301798
TI  - Estrogen Receptor Gene Polymorphisms and Lung Adenocarcinoma Risk in Never
      Smoking Women.
AB  - INTRODUCTION: The association between estrogen receptor (ER) gene polymorphism
      and lung cancer risk is rarely studied. This study aimed to explore the ER gene
      polymorphisms associated with the lung adenocarcinoma risk in never-smoking
      women. METHODS: This study evaluated 532 never-smoking female patients with lung
      adenocarcinoma and 532 healthy controls. The ESR1 and ESR2 single nucleotide
      polymorphism (SNP) data were retrieved from a genome-wide association study.
      Using a multivariate-adjusted logistic regression assay, the associations of ESR1
      and ESR2 SNPs with the lung adenocarcinoma risk were estimated. Expression
      quantitative trait loci analysis was performed to investigate the possible
      functional roles of ER gene SNPs. RESULTS: For ESR1, seven tagged SNPs were
      identified. Among them, rs7753153 and rs985192 were associated with lung
      adenocarcinoma risk (rs7753153: odds ratios [OR], 1.509; 95% confidence intervals
      [CI], 1.168-1.950; rs985192: OR, 1.309; 95% CI, 1.001-1.712). For ESR2, only
      rs3020450 was associated with lung adenocarcinoma risk (OR, 2.110; 95% CI, 1.007
      4.422). Subjects without hormone replacement therapy (HRT) use carrying at-risk
      genotypes had a significantly higher lung adenocarcinoma risk than subjects with
      HRT carrying no at-risk genotypes (rs7753153 GG: OR, 2.133; 95% CI, 1.415-3.216;
      rs985192 AA/AC, OR: 1.752, 95% CI: 1.109-2.768; rs3020450 AG/GG, OR: 7.162, 95%
      CI: 1.608-31.90). Risk genotypes of rs7753153 (p = 0.0248) and rs9479122 (p =
      0.0251) were associated with decreased ESR1 expression. CONCLUSIONS: ER gene SNPs
      are associated with lung adenocarcinoma risk in never-smoking women. The joint
      effects of ER gene SNPs and HRT use on lung adenocarcinoma risk highlight the
      importance of the gene-environment interaction in lung carcinogenesis.

PMID- 26301799
TI  - BRAF Alterations as Therapeutic Targets in Non-Small-Cell Lung Cancer.
AB  - BACKGROUND: Several subsets of non-small-cell lung cancer (NSCLC) are defined by
      molecular alterations acting as tumor drivers, some of them being currently
      therapeutically actionable. The rat sarcoma (RAS)-rapidly accelerated
      fibrosarcoma (RAF)-mitogen-activated protein/extracellular signal-regulated
      kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) pathway
      constitutes an attractive potential target, as v-Raf murine sarcoma viral
      oncogene homolog B (BRAF) mutations occur in 2-4% of NSCLC adenocarcinoma.
      METHODS: Here, we review the latest clinical data on BRAF serine/threonine kinase
      inhibitors in NSCLC. RESULTS: Treatment of V600E BRAF-mutated NSCLC with BRAF
      inhibitor monotherapy demonstrated encouraging antitumor activity. Combination of
      BRAF and MEK inhibitors using dabrafenib and trametinib is under evaluation.
      Preliminary data suggest superior efficacy compared with BRAF inhibitor
      monotherapy. CONCLUSION: Targeting BRAF alterations represents a promising new
      therapeutic approach for a restricted subset of oncogene-addicted NSCLC. Prospect
      ive trials refining this strategy are ongoing. A next step will probably aim at
      combining BRAF inhibitors and immunotherapy or alternatively improve a multilevel
      mitogen-activated protein kinase (MAPK) pathway blockade by combining with ERK
      inhibitors.

PMID- 26301801
TI  - Therapeutic advances in dystonia.
AB  - Knowledge on dystonia has greatly improved recently, because of a renewed effort
      in understanding its cause, pathophysiology, and clinical characterization.
      Different drug classes traditionally have been used for the symptomatic treatment
      of dystonia, more recently surpassed by the introduction of botulinum neurotoxins
      and deep brain stimulation. No curative or disease-modifying treatments are
      available. Recent knowledge regarding the pathophysiology of inherited dystonias
      is highlighting new potential treatment strategies. We review therapeutic
      advances in dystonia that have been published over the last 3 years, particularly
      regarding oral medications, local injections of botulinum neurotoxins, deep brain
      stimulation, and transcranial or epidural brain stimulations. We discuss evidence
      of efficacy, highlight recent advances, and focus on key areas under development.

PMID- 26301800
TI  - Somatic Mutation Spectrum of Non-Small-Cell Lung Cancer in African Americans: A
      Pooled Analysis.
AB  - INTRODUCTION: The mutational profile of non-small-cell lung cancer (NSCLC) has
      become an important tool in tailoring therapy to patients, with clear differences
      according to the population of origin. African Americans (AAs) have higher lung
      cancer incidence and mortality than Caucasians, yet discrepant results have been
      reported regarding the frequency of somatic driver mutations. We hypothesized
      that NSCLC has a distinct mutational profile in this group. METHODS: We collected
      NSCLC samples resected from self-reported AAs in five sites from Tennessee,
      Michigan, and Ohio. Gene mutations were assessed by either SNaPshot or next
      generation sequencing, and ALK translocations were evaluated by fluorescence in
      situ hybridization. RESULTS: Two hundred sixty patients were included, mostly
      males (62.3%) and smokers (86.6%). Eighty-one samples (31.2%) were squamous cell
      carcinomas. The most frequently mutated genes were KRAS (15.4%), epidermal growth
      factor receptor (EGFR, 5.0%), PIK3CA (0.8%), BRAF, NRAS, ERBB2, and AKT1 (0.4%
      each). ALK translocations were detected in two nonsquamous tumors (1.7%),
      totaling 61 cases (23.5%) with driver oncogenic alterations. Among 179
      nonsquamous samples, 54 (30.2%) presented a driver alteration. The frequency of
      driver alterations altogether was lower than that reported in Caucasians, whereas
      no difference was detected in either EGFR or KRAS mutations. Overall survival was
      longer among patients with EGFR mutations. CONCLUSIONS: We demonstrated that
      NSCLC from AAs has a different pattern of somatic driver mutations than from
      Caucasians. The majority of driver alterations in this group are yet to be
      described, which will require more comprehensive panels and assessment of
      noncanonical alterations.

PMID- 26301802
TI  - Lepidotol A from Mesua lepidota Inhibits Inflammatory and Immune Mediators in
      Human Endothelial Cells.
AB  - Phytochemical investigation on the fruits of Mesua lepidota (Calophyllaceae) led
      to the isolation of seven new phenylcoumarin derivatives named lepidotols A-E (1
      5) and lepidotins A and B (6, 7). These structures were elucidated by
      spectroscopic and spectrometric methods including UV, NMR, and HRMS. Lepidotol A
      (1), the major compound, was evaluated for its inhibitory effect on inflammation
      and immunity using endothelial cell-based cellular assays. At 10 MUM, 1 exhibited
      an anti-inflammatory activity, with a significant inhibition of vascular cell
      adhesion molecule 1 and intercellular adhesion molecule 1 expression induced by
      tumor necrosis factor-alpha. Lepidotol A also showed a mild immunosuppressive
      effect, with inhibition of the major histocompatibility complex molecules,
      namely, human leukocyte antigen (HLA)-DR and HLA-E. 

PMID- 26301803
TI  - Sensitivity to emotional scene content outside the focus of attention.
AB  - We investigated whether the emotional content of visual scenes depicting people
      is processed in peripheral vision. Emotional or neutral scene photographs were
      paired with a matched scrambled image for 150ms in peripheral vision (>=5 degrees
      ). The pictures were immediately followed by a digit or letter in a
      discrimination task. Interference (i.e., slowed reaction times) with performance
      in this task indexed the processing resources drawn by the pictures. Twelve types
      of specific emotional scene contents (e.g., erotica or mutilation) were compared.
      Results showed, first, that emotional scenes caused greater interference than
      neutral scenes, in the absence of fixations. This suggests that emotional scenes
      are processed and draw covert attention outside the focus of overt attention.
      Second, interference was similar for female and male participants with pleasant
      scenes (except for erotica), but females were more affected by all types of
      unpleasant scenes than males. This reveals that sensitivity to peripheral vision
      is modulated by sex and affective valence. Third, low-level image properties,
      visual saliency, and size of bodies and faces, were generally equivalent for
      emotional and neutral scenes. This rules out the alternative hypothesis of a
      contribution of non-emotional, purely perceptual factors. 

PMID- 26301804
TI  - Temporal variation of diabetic ketoacidosis and hypoglycemia in adults with type
      1 diabetes: A nationwide cohort study.
AB  - BACKGROUND: Seasonality in health outcomes has long been recognized for
      conditions such as colds and flus. The aim of the present study was to determine
      whether hospitalizations for acute complications of type 1 diabetes (T1D) vary by
      month and season. METHODS: An observational study was performed of national
      administrative health data. Hospitalizations for acute complications in adults
      (aged >=18 years) with T1D were identified using ICD-10 (Canadian revision) codes
      between 2004 and 2010. Monthly and seasonal counts per year were determined for
      the study period. For each acute complication, the ratio of the number of
      observed hospitalizations/expected number of hospitalizations was calculated for
      each month and season per year, adjusting for varied lengths of month, season,
      and year. RESULTS: In all, there were 21 568 hospitalizations for diabetic
      ketoacidosis (DKA) and 5349 hospitalizations for hypoglycemia during the study
      period. December had higher than expected hospitalizations for DKA and March had
      higher than expected hospitalizations for hypoglycemia. There did not appear to
      be variation for either DKA or hypoglycemia hospitalizations by season.
      CONCLUSIONS: The results of the present study suggest temporal variation in
      hospitalizations for DKA and hypoglycemia, and therefore signal important times
      of patient vulnerability. Potential mechanisms underlying this pattern warrant
      further examination. Prevention strategies and resources for patients with T1D
      may need to be increased at specific times during the year.

PMID- 26301805
TI  - It's never too late to save a photoreceptor.
AB  - Recent gene therapy progress has raised the possibility that vision loss caused
      by inherited retinal degeneration can be slowed or prevented. Unfortunately,
      patients are not usually diagnosed until enough degeneration has occurred that
      the deterioration in vision is noticeable. Therefore, effective gene therapy must
      halt degeneration to stabilize and preserve any remaining vision. Gene therapy
      methods currently in human clinical trials rely on subretinal or intravitreal
      injections of adeno-associated virus to deliver the therapeutic gene. To date,
      long-term results in patients treated with subretinal injections for Leber
      congenital amaurosis have been mixed. Proposed limitations include variability in
      the gene delivery method and a possible point of no return, at which treatment
      would be ineffective. In this issue of the JCI, Koch et al. describe a well
      controlled and precise mouse model for testing the ability of gene therapy to
      halt the progress of degeneration. Instead of viral-mediated therapeutic gene
      delivery, the authors induced expression of an integrated transgene at specific
      times during the course of photoreceptor degeneration. In Pde6b-deficient retina,
      this strategy halted degeneration, even when more than 70% of photoreceptors had
      already degenerated. The results of this study demonstrate that retinal
      degeneration can be stopped, even at late stages of disease. 

PMID- 26301806
TI  - Hungry irony.
AB  - Iron-deficient individuals experience a loss of appetite that can be restored
      with iron supplementation. It has been proposed that iron influences the satiety
      hormone leptin; however, a direct link between iron and leptin has remained
      elusive. In this issue of the JCI, Gao and colleagues demonstrate an inverse
      relationship between adipocyte iron and leptin that is mediated by iron-dependent
      activation of cAMP-responsive element binding protein (CREB), the transcription
      factor that represses leptin transcription. Together, the results of this study
      provide a mechanistic connection between dietary iron and the appetite-regulating
      hormone leptin. 

PMID- 26301807
TI  - A robust in vivo model for B cell precursor acute lymphoblastic leukemia.
AB  - B cell precursor acute lymphoblastic leukemia (BCP ALL) is the most common
      malignancy in children. While treatments have improved remarkably over the past
      four decades, resistant disease and late effects that result from cytotoxic
      chemotherapy remain serious problems for individuals with BCP ALL. Improved
      genetic tools have led to the discovery of numerous somatic mutations associated
      with BCP ALL, leading to a framework for the genetic classification of BCP ALL.
      In this issue of the JCI, Duque-Afonso et al. develop an accurate in vivo model
      for BCP ALL that recapitulates the key features of human disease, including
      acquired mutations in genes encoding PAX5 and components of the JAK/STAT pathway.
      The authors further show, as proof of principle, that this model can be used to
      evaluate the efficacy of drugs designed to target specific acquired mutations in
      patients with BCP ALL. 

PMID- 26301808
TI  - The tragic fate of group 3 innate lymphoid cells during HIV-1 infection.
AB  - HIV-1 infection usually leads to systemic chronic inflammation that is associated
      with gut microbial translocation. The recently defined group 3 innate lymphoid
      cells (ILC3s) are critical for maintenance of intestinal barrier function;
      however, it is not clear whether and how HIV-1 infection influences the function
      of these cells. In this issue of the JCI, Zhang and colleagues present compelling
      evidence that the survival and function of ILC3s are dramatically impaired by HIV
      1 infection. The authors provide evidence that HIV-1 infection induces persistent
      activation of plasmacytoid dendritic cells (pDCs) and production of type I IFNs,
      which together increase expression of death receptor CD95 on ILC3s and thereby
      promote subsequent ILC3 apoptosis. Together, these results identify a mechanism
      that explains the impaired intestinal barrier function that results from chronic
      HIV-1 infection and shed light on the role of pDCs in HIV-1 immunopathogenesis
      and therapy. 

PMID- 26301809
TI  - The cortical thickness phenotype of individuals with DISC1 translocation
      resembles schizophrenia.
AB  - BACKGROUND: The disrupted in schizophrenia 1 (DISC1) gene locus was originally
      identified in a Scottish pedigree with a high incidence of psychiatric disorders
      that is associated with a balanced t(1;11)(q42.1;q14.3) chromosomal
      translocation. Here, we investigated whether members of this family carrying the
      t(1;11)(q42.1;q14.3) translocation have a common brain-related phenotype and
      whether this phenotype is similar to that observed in schizophrenia (SCZ), using
      multivariate pattern recognition techniques. METHODS: We measured cortical
      thickness, cortical surface area, subcortical volumes, and regional cerebral
      blood flow (rCBF) in healthy controls (HC) (n = 24), patients diagnosed with SCZ
      (n = 24), patients diagnosed with bipolar disorder (BP) (n = 19), and members of
      the original Scottish family (n = 30) who were either carriers (T+) or
      noncarriers (T-) of the DISC1 translocation. Binary classification models were
      developed to assess the differences and similarities across groups. RESULTS:
      Based on cortical thickness, 72% of the T- group were assigned to the HC group,
      83% of the T+ group were assigned to the SCZ group, and 45% of the BP group were
      classified as belonging to the SCZ group, suggesting high specificity of this
      measurement in predicting brain-related phenotypes. Shared brain-related
      phenotypes between SCZ and T+ individuals were found for cortical thickness only.
      Finally, a classification accuracy of 73% was achieved when directly comparing
      the pattern of cortical thickness of T+ and T- individuals. CONCLUSION: Together,
      the results of this study suggest that the DISC1 translocation may increase the
      risk of psychiatric disorders in this pedigree by affecting neurostructural
      phenotypes such as cortical thickness. FUNDING: This work was supported by the
      National Health Service Research Scotland, the Scottish Translational Medicine
      Research Collaboration, the Innovative Medicines Initiative (IMI), the
      Engineering and Physical Sciences Research Council (EPSRC), The Wellcome Trust,
      the National Institute of Health Research (NIHR), and Pfizer.

PMID- 26301810
TI  - Adipocyte iron regulates leptin and food intake.
AB  - Dietary iron supplementation is associated with increased appetite. Here, we
      investigated the effect of iron on the hormone leptin, which regulates food
      intake and energy homeostasis. Serum ferritin was negatively associated with
      serum leptin in a cohort of patients with metabolic syndrome. Moreover, the same
      inverse correlation was observed in mice fed a high-iron diet. Adipocyte-specific
      loss of the iron exporter ferroportin resulted in iron loading and decreased
      leptin, while decreased levels of hepcidin in a murine hereditary hemochromatosis
      (HH) model increased adipocyte ferroportin expression, decreased adipocyte iron,
      and increased leptin. Treatment of 3T3-L1 adipocytes with iron decreased leptin
      mRNA in a dose-dependent manner. We found that iron negatively regulates leptin
      transcription via cAMP-responsive element binding protein activation (CREB
      activation) and identified 2 potential CREB-binding sites in the mouse leptin
      promoter region. Mutation of both sites completely blocked the effect of iron on
      promoter activity. ChIP analysis revealed that binding of phosphorylated CREB is
      enriched at these two sites in iron-treated 3T3-L1 adipocytes compared with
      untreated cells. Consistent with the changes in leptin, dietary iron content was
      also directly related to food intake, independently of weight. These findings
      indicate that levels of dietary iron play an important role in regulation of
      appetite and metabolism through CREB-dependent modulation of leptin expression. 

PMID- 26301811
TI  - DNA replication stress underlies renal phenotypes in CEP290-associated Joubert
      syndrome.
AB  - Juvenile ciliopathy syndromes that are associated with renal cysts and premature
      renal failure are commonly the result of mutations in the gene encoding
      centrosomal protein CEP290. In addition to centrosomes and the transition zone at
      the base of the primary cilium, CEP290 also localizes to the nucleus; however,
      the nuclear function of CEP290 is unknown. Here, we demonstrate that reduction of
      cellular CEP290 in primary human and mouse kidney cells as well as in zebrafish
      embryos leads to enhanced DNA damage signaling and accumulation of DNA breaks ex
      vivo and in vivo. Compared with those from WT mice, primary kidney cells from
      Cep290-deficient mice exhibited supernumerary centrioles, decreased replication
      fork velocity, fork asymmetry, and increased levels of cyclin-dependent kinases
      (CDKs). Treatment of Cep290-deficient cells with CDK inhibitors rescued DNA
      damage and centriole number. Moreover, the loss of primary cilia that results
      from CEP290 dysfunction was rescued in 3D cell culture spheroids of primary
      murine kidney cells after exposure to CDK inhibitors. Together, our results
      provide a link between CEP290 and DNA replication stress and suggest CDK
      inhibition as a potential treatment strategy for a wide range of ciliopathy
      syndromes. 

PMID- 26301812
TI  - Plasmacytoid dendritic cells promote HIV-1-induced group 3 innate lymphoid cell
      depletion.
AB  - Group 3 innate lymphoid cells (ILC3s) have demonstrated roles in promoting
      antibacterial immunity, maintaining epithelial barrier function, and supporting
      tissue repair. ILC3 alterations are associated with chronic inflammation and
      inflammatory disease; however, the characteristics and relevant regulatory
      mechanisms of this cell population in HIV-1 infection are poorly understood due
      in part to a lack of a robust model. Here, we determined that functional human
      ILC3s develop in lymphoid organs of humanized mice and that persistent HIV-1
      infection in this model depletes ILC3s, as observed in chronic HIV-1-infected
      patients. In HIV-1-infected mice, effective antiretroviral therapy reversed the
      loss of ILC3s. HIV-1-dependent reduction of ILC3s required plasmacytoid dendritic
      cells (pDCs), IFN-I, and the CD95/FasL pathway, as targeted depletion or blockade
      of these prevented HIV-1-induced ILC3 depletion in vivo and in vitro,
      respectively. Finally, we determined that HIV-1 infection induces CD95 expression
      on ILC3s via a pDC- and IFN-I-dependent mechanism that sensitizes ILC3s to
      undergo CD95/FasL-mediated apoptosis. We conclude that chronic HIV-1 infection
      depletes ILC3s through pDC activation, induction of IFN-I, and CD95-mediated
      apoptosis. 

PMID- 26301813
TI  - Halting progressive neurodegeneration in advanced retinitis pigmentosa.
AB  - Hereditary retinal degenerative diseases, such as retinitis pigmentosa (RP), are
      characterized by the progressive loss of rod photoreceptors followed by loss of
      cones. While retinal gene therapy clinical trials demonstrated temporary
      improvement in visual function, this approach has yet to achieve sustained
      functional and anatomical rescue after disease onset in patients. The lack of
      sustained benefit could be due to insufficient transduction efficiency of viral
      vectors ("too little") and/or because the disease is too advanced ("too late") at
      the time therapy is initiated. Here, we tested the latter hypothesis and
      developed a mouse RP model that permits restoration of the mutant gene in all
      diseased photoreceptor cells, thereby ensuring sufficient transduction
      efficiency. We then treated mice at early, mid, or late disease stages. At all 3
      time points, degeneration was halted and function was rescued for at least 1
      year. Not only do our results demonstrate that gene therapy effectively preserves
      function after the onset of degeneration, our study also demonstrates that there
      is a broad therapeutic time window. Moreover, these results suggest that RP
      patients are treatable, despite most being diagnosed after substantial
      photoreceptor loss, and that gene therapy research must focus on improving
      transduction efficiency to maximize clinical impact. 

PMID- 26301814
TI  - Selective Treg reconstitution during lymphopenia normalizes DC costimulation and
      prevents graft-versus-host disease.
AB  - Regulatory T cells (Tregs) have been shown to enhance immune reconstitution and
      prevent graft-versus-host disease (GVHD) after hematopoietic stem cell
      transplantation; however, it is unclear how Tregs mediate these effects. Here, we
      developed a model to examine the mechanism of Treg-dependent regulation of immune
      reconstitution. Lymphopenic mice were selectively reconstituted with Tregs prior
      to transfer of conventional CD4+ T cells. Full Treg reconstitution prevented the
      rapid oligoclonal proliferation that gives rise to pathogenic CD4 effector T
      cells, while preserving the slow homeostatic form of lymphopenia-induced
      peripheral expansion that repopulates a diverse peripheral T cell pool. Treg
      mediated CTLA-4-dependent downregulation of CD80/CD86 on DCs was critical for
      inhibition of rapid proliferation and was a function of the Treg/DC ratio
      achieved by reconstitution. In an allogeneic BM transplant model, selective Treg
      reconstitution before T cell transfer also normalized DC costimulation and
      provided complete protection against GVHD. In contrast, cotransfer of Tregs was
      not protective. Our results indicate that achieving optimal recovery from
      lymphopenia should aim to improve early Treg reconstitution in order to increase
      the relative number of Tregs to DCs and thereby inhibit spontaneous oligoclonal T
      cell proliferation. 

PMID- 26301815
TI  - Skin-derived neural precursors competitively generate functional myelin in adult
      demyelinated mice.
AB  - Induced pluripotent stem cell-derived (iPS-derived) neural precursor cells may
      represent the ideal autologous cell source for cell-based therapy to promote
      remyelination and neuroprotection in myelin diseases. So far, the therapeutic
      potential of reprogrammed cells has been evaluated in neonatal demyelinating
      models. However, the repair efficacy and safety of these cells has not been well
      addressed in the demyelinated adult CNS, which has decreased cell plasticity and
      scarring. Moreover, it is not clear if these induced pluripotent-derived cells
      have the same reparative capacity as physiologically committed CNS-derived
      precursors. Here, we performed a side-by-side comparison of CNS-derived and skin
      derived neural precursors in culture and following engraftment in murine models
      of adult spinal cord demyelination. Grafted induced neural precursors exhibited a
      high capacity for survival, safe integration, migration, and timely
      differentiation into mature bona fide oligodendrocytes. Moreover, grafted skin
      derived neural precursors generated compact myelin around host axons and restored
      nodes of Ranvier and conduction velocity as efficiently as CNS-derived precursors
      while outcompeting endogenous cells. Together, these results provide important
      insights into the biology of reprogrammed cells in adult demyelinating conditions
      and support use of these cells for regenerative biomedicine of myelin diseases
      that affect the adult CNS. 

PMID- 26301817
TI  - P.N.E.I.: life and death of skin cells. A new paradigm in the treatment of
      vitiligo: the low dose cytokines therapy.

PMID- 26301816
TI  - Comparative genomics reveals multistep pathogenesis of E2A-PBX1 acute
      lymphoblastic leukemia.
AB  - Acute lymphoblastic leukemia (ALL) is the most common childhood cancer; however,
      its genetic diversity limits investigation into the molecular pathogenesis of
      disease and development of therapeutic strategies. Here, we engineered mice that
      conditionally express the E2A-PBX1 fusion oncogene, which results from
      chromosomal translocation t(1;19) and is present in 5% to 7% of pediatric ALL
      cases. The incidence of leukemia in these mice varied from 5% to 50%, dependent
      on the Cre-driving promoter (Cd19, Mb1, or Mx1) used to induce E2A-PBX1
      expression. Two distinct but highly similar subtypes of B cell precursor ALLs
      that differed by their pre-B cell receptor (pre-BCR) status were induced and
      displayed maturation arrest at the pro-B/large pre-B II stages of
      differentiation, similar to human E2A-PBX1 ALL. Somatic activation of E2A-PBX1 in
      B cell progenitors enhanced self-renewal and led to acquisition of multiple
      secondary genomic aberrations, including prominent spontaneous loss of Pax5. In
      preleukemic mice, conditional Pax5 deletion cooperated with E2A-PBX1 to expand
      progenitor B cell subpopulations, increasing penetrance and shortening leukemia
      latency. Recurrent secondary activating mutations were detected in key signaling
      pathways, most notably JAK/STAT, that leukemia cells require for proliferation.
      These data support conditional E2A-PBX1 mice as a model of human ALL and suggest
      targeting pre-BCR signaling and JAK kinases as potential therapeutic strategies. 

PMID- 26301818
TI  - Characterization of the Aroma-Active, Phenolic, and Lipid Profiles of the
      Pistachio (Pistacia vera L.) Nut as Affected by the Single and Double Roasting
      Process.
AB  - The pistachio (Pistacia vera L.) nut is one of the most widely consumed edible
      nuts in the world. However, it is the roasting process that makes the pistachio
      commercially viable and valuable as it serves as the key step to improving the
      nut's hallmark sensory characteristics including flavor, color, and texture.
      Consequently, the present study explores the effects of the single-roasting and
      double-roasting process on the pistachio's chemical composition, specifically
      aroma-active compounds, polyphenols, and lipids. Results showed the total
      polyphenol content of increased with the roasting treatment; however, not all
      phenolic compounds demonstrated this behavior. With regard to the aroma and aroma
      active compounds, the results indicated that roasting process results in the
      development of characteristics and pleasant aroma of pistachio samples due to the
      Maillard reaction. With regard to lipids, the pistachio roasting treatment
      reduced the concentration of CN38 diacylglycerides while increasing the amount of
      elaidic acid. 

PMID- 26301819
TI  - Mono-, Di-, and Trifluoroalkyl Substituent Effects on the Torquoselectivities of
      Cyclobutene and Oxetene Electrocyclic Ring Openings.
AB  - The reactivities and torquoselectivities of electrocyclic ring opening reactions
      of fluoromethyl-substituted cyclobutenes and oxetenes were studied with M06-2X
      density functional theory. The torquoselectivities of a series of mono-, di-, and
      trifluoromethylcyclobutenes and oxetenes result from the interplay of favorable
      orbital interactions and closed-shell repulsions. When the substituent rotates
      inward, there can be a favorable interaction between the breaking sigma(CO) bond
      and the sigma(CF)* orbital (sigma(CO) -> sigma(CF)*) of the fluoromethyl group in
      fluoromethyloxetenes. The preference for rotation of a fluoromethyl group is
      decreased in trifluoromethyloxetenes because closed-shell repulsions between the
      breaking sigma(CO) bond and trifluoromethyl substituent orbitals compete with the
      sigma(CO) -> sigma(CF)* interaction.

PMID- 26301820
TI  - Detection of zinc finger protein (EGR1) based on electrogenerated
      chemiluminescence from singlet oxygen produced in a nanoclay-supported porphyrin
      environment.
AB  - Early growth response protein 1 (EGR1), as a characteristic example of zinc
      finger proteins, acts as a transcription factor in eukaryotic cells, mediating
      protein-protein interactions. Here, a novel electrochemiluminescence (ECL)-based
      protocol for EGR1 assay was developed with a new eco-friendly emitter: singlet
      oxygen produced in the vicinity of nanoclay-supported zinc proto-porphyrin IX
      (ZnPPIX). Its electrochemical reduction stimulates an intense monochromic CL
      irradiation at 644 nm from the dissolved oxygen as endogenous coreactant in the
      aqueous solution. This ECL derivation was rationalized via hyphenated
      spectroscopy and theoretical calculation. To promote hydrophilicity and solid
      state immobilization of porphyrins, the lamellar artificial laponite was employed
      as a nanocarrier owning to its large specific area without the blackbody effect.
      The facile exfoliation of laponite produced quality monolayered nanosheets and
      facilitated the adsorption and flattening of PPIX upon the surface, resulting in
      a highly efficient ECL emission. Based on the release of Zn(2+) in zinc finger
      domains of EGR1 upon contact with the ECL-inactive PPIX, which was monitored by
      circular dichroism and UV-absorption, a sensitive Zn(2+)-selective electrode for
      the "signal-on" detection of EGR1 was prepared with a detection limit down to
      0.48 pg mL(-1) and a linearity over 6 orders of magnitude. The proposed porphyrin
      based ECL system thus infused fresh blood into the traditional ECL family,
      showing great promise in bioassays of structural Zn(II) proteins and zinc finger
      binding nucleotides. 

PMID- 26301822
TI  - Hippocampal signaling pathways are involved in stress-induced impairment of
      memory formation in rats.
AB  - Stress is a potent modulator of hippocampal-dependent memory formation. The aim
      of the present study was to assess the role of hippocampal signaling pathways in
      stress-induced memory impairment in male Wistar rats. The animals were exposed to
      acute elevated platform (EP) stress and memory formation was measured by a step
      through type passive avoidance task. The results indicated that post-training or
      pre-test exposure to EP stress impaired memory consolidation or retrieval
      respectively. Using western blot analysis, it was found that memory retrieval was
      associated with the increase in the levels of phosphorylated cAMP-responsive
      element binding protein (P-CREB), peroxisome proliferator-activated receptor
      gamma coactivator-1alpha (PGC-1alpha) and its downstream targets in the
      hippocampus. In contrast, the stress exposure decreased the hippocampal levels of
      these proteins. In addition, stress-induced impairment of memory consolidation or
      retrieval was associated with the decrease in the P-CREB/CREB ratio and the PGC
      1alpha level in the hippocampus. On the other hand, the hippocampal level of
      nuclear factor E2-related factor 2 (Nrf2) and gamma-glutamylcysteine synthetase
      (gamma-GCS) which are the master regulators of defense system were decreased by
      the stress exposure. The increased hippocampal levels of Nrf2 and it's downstream
      was observed during memory retrieval, while stress-induced impairment of memory
      consolidation or retrieval inhibited this hippocampal signaling pathway. Overall,
      these findings suggest that down-regulation of CREB/PGC-1alpha signaling cascade
      and Nrf2 antioxidant pathways in the hippocampus may be associated with memory
      impairment induced by stress. 

PMID- 26301821
TI  - A novel mechanism for the anticonvulsant effect of furosemide in rat hippocampus
      in vitro.
AB  - Though both in vivo and in vitro studies have demonstrated an anticonvulsant
      effect of the loop diuretic furosemide, the precise mechanism behind this effect
      is still debated. The current study investigates the effect of furosemide on Cs
      induced epileptiform activity (Cs-FP) evoked in area CA1 of rat hippocampal
      slices in the presence of Cs(+) (5mM) and ionotropic glutamatergic and GABAergic
      receptor antagonists. As this model diverges in several respects from other
      epilepsy models it can offer new insight into the mechanism behind the
      anticonvulsive effect of furosemide. The present study shows that furosemide
      suppresses the Cs-FP in a dose-dependent manner with a near complete block at
      concentrations >= 1.25 mM. Because furosemide targets several types of ion
      transporters we examined the effect of more selective antagonists. Bumetanide (20
      MUM), which selectively inhibits the Na-K-2Cl co-transporter (NKCC1), had no
      significant effect on the Cs-FP. VU0240551 (10 MUM), a selective antagonist of
      the K-Cl co-transporter (KCC2), reduced the ictal-like phase by 51.73 +/- 8.5%
      without affecting the interictal-like phase of the Cs-FP. DIDS (50 MUM), a
      nonselective antagonist of Cl(-)/HCO3(-)-exchangers, Na(+)-HCO3(-)
      cotransporters, chloride channels and KCC2, suppressed the ictal-like phase by
      60.8 +/- 8.1% without affecting the interictal-like phase. At 500 MUM, DIDS
      completely suppressed the Cs-FP. Based on these results we propose that the
      anticonvulsant action of furosemide in the Cs(+)-model is exerted through
      blockade of the neuronal KCC2 and Na(+)-independent Cl(-)/HCO3(-)-exchanger (AE3)
      leading to stabilization of the activity-induced intracellular acidification in
      CA1 pyramidal neurons.

PMID- 26301823
TI  - CIH-induced neurocognitive impairments are associated with hippocampal Ca(2+)
      overload, apoptosis, and dephosphorylation of ERK1/2 and CREB that are mediated
      by overactivation of NMDARs.
AB  - Chronic intermittent hypoxia (CIH) is commonly seen in patients with obstructive
      sleep apnea, and has been hypothesized to underlie the neurocognitive dysfunction
      in these patients. However, its cellular and molecular mechanisms remain to be
      defined. The present study aimed to investigate, in a mouse CIH model, the role
      of NMDA receptor (NMDAR) activation in mediating the CIH-induced neurocognitive
      impairments, caspase expression and dysregulated Ca(2+) signaling pathways in
      hippocampus. Male ICR mice (n=45) were exposed to CIH (8h/day) or room air
      (control) for 4 weeks. After 4-week treatment, neurobehavioral assessments were
      performed by Morris water maze test, hippocampal [Ca(2+)]i was evaluated by flow
      cytometry; and protein expressions of caspase-3, caspase-9, PARP, p-ERK1/2 and p
      CREB in hippocampus were measured by Western blotting. Our results showed that,
      compared to control animals, 4-week exposure to CIH produced significant spatial
      learning and memory impairments in CIH mice. Increased caspase expression in
      hippocampus was observed in CIH mice associated with significant elevation of
      [Ca(2+)]i and dephosphorylation of ERK and CREB expression. When the NMDAR
      antagonist memantine was administered by intraperitoneal injection prior to daily
      exposure to CIH, at a sub-therapeutic dose of 5mg/kg/day not shown to impact the
      neurobehavioral performance in control animals, the neurocognitive impairments as
      well as the neurobiochemical changes were abolished or normalized in the CIH
      mice. Our study suggests that overactivation of NMDARs and the Ca(2+) overload
      dependent ERK/CREB dysregulation is one of the important mechanisms in mediating
      the CIH-induced neurocognitive impairments. 

PMID- 26301824
TI  - Hyperbaric oxygen preconditioning attenuates neuroinflammation after
      intracerebral hemorrhage in rats by regulating microglia characteristics.
AB  - Intracerebral Hemorrhage (ICH) results in a detrimental neurologic disorder with
      complicated secondary brain injury. Hyperbaric oxygen preconditioning (HBOP) may
      be a safe and effective therapeutic method for ICH victims. Our previous studies
      have demonstrated that HBOP induces neuroprotection in cerebral ischemia and
      traumatic brain injury. This study aimed to investigate whether HBOP could
      alleviate neuroinflammation by regulating changes in microglia characteristics in
      a rat model of ICH. ICH was induced by autologous arterial blood injection, and
      animals were sacrificed at 12, 24, and 72 h post injury. We measured motor
      function and brain water content to evaluate the extent of inflammation. Fluoro
      Jade C and TNF-alpha staining was used to characterize neuronal degeneration and
      neuroinflammatory cytokines, and immunofluorescence staining was performed for
      CD11b to show activated microglia and Iba-1 to show microglia. Our results
      indicate that motor dysfunction and brain water content are alleviated by HBOP,
      and Fluoro-Jade C staining demonstrates that neuron degeneration decreased in the
      HBOP group. The growth of Iba-1-positive microglia decreased in the HBOP group.
      Moreover, TNF-alpha was dynamically reduced in the HBOP group compared with the
      ICH group. CD11b-Iba-1 double staining demonstrated that the ratio of CD11b and
      Iba-1 was significantly decreased in the HBOP group. Overall, the data
      demonstrated that HBOP could significantly alleviate the ICH-induced
      neuroinflammation by regulating microglia characteristics changing. The
      phenomenon may propel the progress of the relation between microglia and HBOP and
      represent a novel target for ICH treatment.

PMID- 26301826
TI  - Infection Efficiency of Four Phytophthora infestans Clonal Lineages and DNA-Based
      Quantification of Sporangia.
AB  - The presence and abundance of pathogen inoculum is with host resistance and
      environmental conditions a key factor in epidemic development. Therefore, several
      spore-sampling devices have been proposed to monitor pathogen inoculum above
      fields. However, to make spore sampling more reliable as a management tool and to
      facilitate its adoption, information on infection efficiency and molecular tools
      for estimating airborne sporangia concentration are needed. Experiments were thus
      undertaken in a growth chamber to study the infection efficiency of four clonal
      lineages of P. infestans (US-8, US-11, US-23, and US-24) by measuring the
      airborne sporangia concentration and resulting disease intensity. The
      relationship between the airborne sporangia concentration and the number of
      lesions per leaf was exponential. For the same concentration, the sporangia of US
      23 caused significantly more lesions than the sporangia of the other clonal
      lineages did. Under optimal conditions, an airborne sporangia concentration of 10
      sporangia m-3 for US-23 was sufficient to cause one lesion per leaf, whereas for
      the other clonal lineages, it took 15 to 25 sporangia m-3 to reach the same
      disease intensity. However, in terms of diseased leaf area, there was no
      difference between clonal lineages US-8, US-23 and US-24. Also, a sensitive
      quantitative real-time polymerase chain reaction (qPCR) tool was developed to
      quantify P. infestans airborne sporangia with detection sensitivity of one
      sporangium. The specificity of the qPCR assay was rigorously tested for airborne
      inoculum and was either similar to, or an improvement on, other published PCR
      assays. This assay allows rapid and reliable detection and quantification of P.
      infestans airborne sporangia and thereby, facilitates the implementation of
      spores-sampling network. 

PMID- 26301827
TI  - Mechanism of Bursting Taylor Bubbles at Free Surfaces.
AB  - Collapse of a Taylor bubble inside a pipe at the free surface of a liquid is
      studied experimentally using speed imaging camera and illumination and subsequent
      image analysis. Three different fluids, water, glycerin, and silicone oil, are
      employed in the experiments. For all conditions studied herein, the bubble
      punctures at the free surface to form two thin films, i.e., one covering the
      cross-section of the tube near the free surface and one along the tube wall in
      the vertical direction. Surface tension acts to collapse the first film, which
      widens the punctured hole in the outward radial direction, thereby feeding the
      liquid in the vertical film. After the shrinking of the radial film, gravity
      causes the collapse of the vertical film, which generates a tiny jet of liquid at
      the end of collapse. Experiments with different fluids show a drastic change in
      shape and thickness of the vertical film that leads to higher drainage time.
      Analysis of time scale for the drainage of the horizontal film exhibits a
      favorable match with experiments. Finally, evolution of the vertical film is
      analyzed using a simple hydrodynamic model to estimate the order magnitude of
      time taken to collapse, which compares well with processed image data from
      experiments. 

PMID- 26301825
TI  - Lineage, fate, and fate potential of NG2-glia.
AB  - NG2 cells represent a fourth major glial cell population in the mammalian central
      nervous system (CNS). They arise from discrete germinal zones in mid-gestation
      embryos and expand to occupy the entire CNS parenchyma. Genetic fate mapping
      studies have shown that oligodendrocytes and a subpopulation of ventral
      protoplasmic astrocytes arise from NG2 cells. This review describes recent
      findings on the fate and fate potential of NG2 cells under physiological and
      pathological conditions. We discuss age-dependent changes in the fate and fate
      potential of NG2 cells and possible mechanisms that could be involved in
      restricting their oligodendrocyte differentiation or fate plasticity. This
      article is part of a Special Issue entitled SI:NG2-glia(Invited only).

PMID- 26301828
TI  - Learning style versus time spent studying and career choice: Which is associated
      with success in a combined undergraduate anatomy and physiology course?
AB  - The VARK learning style is a pedagogical focus in health care education. This
      study examines relationships of course performance vs. VARK learning preference,
      study time, and career plan among students enrolled in an undergraduate anatomy
      and physiology course at a large urban university. Students (n = 492) from the
      fall semester course completed a survey consisting of the VARK questionnaire,
      gender, academic year, career plans, and estimated hours spent per week in
      combined classroom and study time. Seventy-eight percent of students reported
      spending 15 or fewer hours per week studying. Study time and overall course score
      correlated significantly for the class as a whole (r = 0.111, P = 0.013), which
      was mainly due to lecture (r = 0.118, P = 0.009) performance. No significant
      differences were found among students grouped by learning styles. When corrected
      for academic year, overall course scores (mean +/- SEM) for students planning to
      enter dentistry, medicine, optometry or pharmacy (79.89 +/- 0.88%) were
      significantly higher than those of students planning to enter physical or
      occupational therapies (74.53 +/- 1.15%; P = 0.033), as well as nurse/physician
      assistant programs (73.60 +/- 1.3%; P = 0.040). Time spent studying was not
      significantly associated with either learning style or career choice. Our
      findings suggest that specific career goals and study time, not learning
      preferences, are associated with better performance among a diverse group of
      students in an undergraduate anatomy and physiology course. However, the extent
      to which prior academic preparation, cultural norms, and socioeconomic factors
      influenced these results requires further investigation.

PMID- 26301830
TI  - Biological half-life of radioactive cesium in Japanese rockfish Sebastes cheni
      contaminated by the Fukushima Daiichi nuclear power plant accident.
AB  - Since the Fukushima accident in March 2011 the concentration of radioactive
      cesium in Japanese rockfish (Sebastes cheni) has been decreasing slower than
      other fish species. The aim of this study was therefore to investigate the
      possibility of slow elimination rate (i.e., relatively longer Tb) as one of the
      reasons for the slow decrease in (137)Cs concentrations in Japanese rockfish (S.
      cheni). To do this, we reared twenty-three individuals of this species for a
      period of about 1 year, during which time we measured the (137)Cs concentrations
      and gamma-ray spectra 14 times by using a high-efficiency NaI(Tl) scintillator.
      We then examined the relationship between the (137)Cs concentrations and the
      total length of each individual. We estimated the biological half-life (Tb, day)
      for each individual using the total number of (137)Cs counts in the energy
      region, and examined the effects of total length and (137)Cs concentration on Tb
      by generalized linear model (GLM). We also examined the effect of sex, total
      length, seawater temperature, and the (137)Cs concentration of seawater on
      temporal changes in the (137)Cs count reduction rate by GLM. There was no clear
      relationship between the corrected whole-body (137)Cs concentrations and the
      total length in females, however there was a significant positive correlation
      between these two variables in males. The difference between males and females
      may be attributable to variation in the degree of dilution because of variable
      growth of individuals, and suggests that the (137)Cs concentrations of small
      individuals may be greatly diluted because of faster growth. However, there was
      no significant difference in Tb between sexes. The mean Tb (+/-SD) in all
      individuals was 269 (+/-39) days; this Tb value is 2.7-5.4 times longer than past
      Tb values (marine fish: 50-100 days), and is thought to be one of the reasons for
      the slower decrease in (137)Cs concentrations in this species than other fish
      species on the coast of Fukushima. The GLM showed significant effects of both
      total length and (137)Cs concentration on Tb, which may reflect a reduction in
      the metabolic rate with increased body size (i.e., aging) and gradient of
      concentration against seawater. The GLM also showed a significant positive effect
      of seawater temperature on the reduction rate of the (137)Cs counts (D, day(-1)).
      Therefore, D was clearly related to seasonal variations in the temperature of
      seawater, and this relationship may be attributable to changes in the metabolic
      rate that are controlled by variations in the seawater temperature. From these
      measurements, we examined the processes that control reductions in (137)Cs
      radioactivity. 

PMID- 26301831
TI  - An investigation into heterogeneity in a single vein-type uranium ore deposit:
      Implications for nuclear forensics.
AB  - Minor element composition and rare earth element (REE) concentrations in nuclear
      materials are important as they are used within the field of nuclear forensics as
      an indicator of sample origin. However recent studies into uranium ores and
      uranium ore concentrates (UOCs) have shown significant elemental and isotopic
      heterogeneity from a single mine site such that some sites have shown higher
      variation within the mine site than that seen between multiple sites. The
      elemental composition of both uranium and gangue minerals within ore samples
      taken along a single mineral vein in South West England have been measured and
      reported here. The analysis of the samples was undertaken to determine the extent
      of the localised variation in key elements. Energy Dispersive X-ray spectroscopy
      (EDS) was used to analyse the gangue mineralogy and measure major element
      composition. Minor element composition and rare earth element (REE)
      concentrations were measured by Electron Probe Microanalysis (EPMA). The results
      confirm that a number of key elements, REE concentrations and patterns used for
      origin location do show significant variation within mine. Furthermore
      significant variation is also visible on a meter scale. In addition three
      separate uranium phases were identified within the vein which indicates multiple
      uranium mineralisation events. In light of these localised elemental variations
      it is recommended that representative sampling for an area is undertaken prior to
      establishing the REE pattern that may be used to identify the originating mine
      for an unknown ore sample and prior to investigating impact of ore processing on
      any arising REE patterns. 

PMID- 26301829
TI  - Self-Regulation of Anterior Insula with Real-Time fMRI and Its Behavioral Effects
      in Obsessive-Compulsive Disorder: A Feasibility Study.
AB  - INTRODUCTION: Obsessive-compulsive disorder (OCD) is a common and chronic
      condition that can have disabling effects throughout the patient's lifespan.
      Frequent symptoms among OCD patients include fear of contamination and washing
      compulsions. Several studies have shown a link between contamination fears,
      disgust over-reactivity, and insula activation in OCD. In concordance with the
      role of insula in disgust processing, new neural models based on neuroimaging
      studies suggest that abnormally high activations of insula could be implicated in
      OCD psychopathology, at least in the subgroup of patients with contamination
      fears and washing compulsions. METHODS: In the current study, we used a Brain
      Computer Interface (BCI) based on real-time functional magnetic resonance imaging
      (rtfMRI) to aid OCD patients to achieve down-regulation of the Blood Oxygenation
      Level Dependent (BOLD) signal in anterior insula. Our first aim was to
      investigate whether patients with contamination obsessions and washing
      compulsions can learn to volitionally decrease (down-regulate) activity in the
      insula in the presence of disgust/anxiety provoking stimuli. Our second aim was
      to evaluate the effect of down-regulation on clinical, behavioural and
      physiological changes pertaining to OCD symptoms. Hence, several pre- and post
      training measures were performed, i.e., confronting the patient with a
      disgust/anxiety inducing real-world object (Ecological Disgust Test), and
      subjective rating and physiological responses (heart rate, skin conductance
      level) of disgust towards provoking pictures. RESULTS: Results of this pilot
      study, performed in 3 patients (2 females), show that OCD patients can gain self
      control of the BOLD activity of insula, albeit to different degrees. In two
      patients positive changes in behaviour in the EDT were observed following the
      rtfMRI trainings. Behavioural changes were also confirmed by reductions in the
      negative valence and in the subjective perception of disgust towards symptom
      provoking images. CONCLUSION: Although preliminary, results of this study
      confirmed that insula down-regulation is possible in patients suffering from OCD,
      and that volitional decreases of insula activation could be used for symptom
      alleviation in this disorder.

PMID- 26301832
TI  - Accumulation and translocation peculiarities of (137)Cs and (40)K in the soil-
      plant system.
AB  - Long-term investigations (1996-2008) were conducted into the (137)Cs and (40)K in
      the soil of forests, swamps and meadows in different regions of Lithuania, as
      well as in the plants growing in these media. The (137)Cs and (40)K activity
      concentrations, the (137)Cs/(40)K activity concentration ratio and accumulation,
      and translocation in the system, i.e. from the soil to plant roots to above
      ground plant part of these radionuclides, were evaluated after gamma
      spectrometric measurements using a high purity germanium (HPGe) detector. Based
      on the obtained data, it can be asserted that in the tested plant species, the
      (137)Cs and (40)K accumulation, the transfer from soil to roots and translocation
      within the plants depend on the plant species and environmental ecological
      conditions. The (137)Cs/(40)K activity concentration ratios in the same plant
      species in different regions of Lithuania are different and this ratio depends on
      the biotope (forest, swamp or meadow) in which the plant grows and on the
      location of the growing region. Based on the determined trends of statistically
      reliable inverse dependence between the activity concentrations in both soil and
      plants, it can be stated that the exchange of (137)Cs and (40)K in plants and
      soil is different. Different accumulations and translocations of investigated
      radionuclides in the same plant species indicate diverse biological metabolism of
      (137)Cs and its chemical analogue (40)K in plants. A competitive relationship
      exists between (137)Cs and (40)K in plants as well as in the soil. 

PMID- 26301833
TI  - Detection of synthetic cathinones in victims of sexual assault.
AB  - Drug facilitated sexual assault (DFSA) can be defined as sexual activity
      occurring whereby the victim is incapacitated by drugs and/or alcohol and thereby
      unable to consent. A new wave of designer drugs is emerging in the community at
      large and one group, the synthetic cathinones, is described in this study.
      Analyzing urine samples from reported sexual assaults submitted to the University
      of Miami Toxicology Lab in 2013 determined that methylone has become a popular
      drug encountered in these cases. Derivatization of these synthetic cathinones
      enabled a validated a qualitative method to identify ten different designer
      drugs. Of the forty-five sexual assault samples submitted, 13% were positive for
      synthetic cathinones without any toxicological finding of ethanol, GHB or
      ketamine. This study illustrates the recent correlation of drug-facilitated
      sexual assaults and the use of synthetic cathinones. 

PMID- 26301834
TI  - Chemical Modification of Polyisobutylene Succinimide Dispersants and
      Characterization of Their Associative Properties.
AB  - The secondary amines found in b-PIBSI dispersants prepared by attaching two
      polyisobutylene chains to a polyamine core via two succinimide moieties were
      reacted with ethylene carbonate (EC). The reaction generated urethane bonds on
      the polyamine core to yield the modified b-PIBSI dispersants (Mb-PIBSI). Five
      dispersants were prepared by reacting 2 molar equivalent (meq) of polyisobutylene
      terminated at one end with a succinic anhydride moiety (PIBSA) with 1 meq of
      hexamethylenediamine (HMDA), diethylenetriamine (DETA), triethylenetetramine
      (TETA), tetraethylenepentamine (TEPA), and pentaethylenehexamine (PEHA) to yield
      the corresponding b-PIBSI dispersants. Characterization of the level of secondary
      amine modification for the Mb-PIBSI dispersants with traditional techniques such
      as FTIR and (1)H NMR spectroscopies was greatly complicated by interactions
      between the carbonyls of the succinimide groups and unreacted secondary amines of
      the Mb-PIBSI dispersants. Therefore, an alternative procedure was developed based
      on fluorescence quenching of the succinimides by secondary amines and urethane
      groups. The procedure took advantage of the fact that the succinimide
      fluorescence of the Mb-PIBSI dispersants was quenched much more efficiently by
      secondary amines than by the urethane groups that resulted from the EC
      modification of the amines. While EC modification did not proceed for b-PIBSI
      DETA and b-PIBSI-TETA certainly due to steric hindrance, 60 and 70% of the
      secondary amines found in the longer polyamine core of b-PIBSI-TEPA and b-PIBSI
      PEHA had reacted with EC as determined by the fluorescence quenching analysis.
      Furthermore, the ability of the Mb-PIBSI dispersants to adsorb at the surface of
      carbon black particles used as mimic of the carbonaceous particles typically
      found in engine oils was compared to that of their unmodified analogues. 

PMID- 26301835
TI  - A Computational Study on the Ground and Excited States of Nickel Silicide.
AB  - Nickel silicide has been studied with a range of computational methods to
      determine the nature of the Ni-Si bond. Additionally, the physical effects that
      need to be addressed within calculations to predict the equilibrium bond length
      and bond dissociation energy within experimental error have been determined. The
      ground state is predicted to be a (1)Sigma(+) state with a bond order of 2.41
      corresponding to a triple bond with weak pi bonds. It is shown that calculation
      of the ground state equilibrium geometry requires a polarized basis set and
      treatment of dynamic correlation including up to triple excitations with CR
      CCSD(T)L resulting in an equilibrium bond length of only 0.012 A shorter than the
      experimental bond length. Previous calculations of the bond dissociation energy
      resulted in energies that were only 34.8% to 76.5% of the experimental bond
      dissociation energy. It is shown here that use of polarized basis sets, treatment
      of triple excitations, correlation of the valence and subvalence electrons, and a
      Lambda coupled cluster approach is required to obtain a bond dissociation energy
      that deviates as little as 1% from experiment. 

PMID- 26301836
TI  - Mixtures of catanionic surfactants can be superspreaders: Comparison with
      trisiloxane superspreader.
AB  - HYPOTHESIS: Mixed solutions of cationic and anionic surfactants show considerable
      synergism in their wetting behaviour, but their spreading is affected
      considerably by the phase separation processes. The valuable information about
      wetting properties of synergetic mixtures can be obtained by using mixtures in
      which phase separation occurs at concentrations above cmc. EXPERIMENTS: Spreading
      properties of mixed solutions of cationic and anionic surfactants over highly
      hydrophobic substrate such as polyethylene are investigated and compared with
      those for trisiloxane superspreader. Experiments are performed at relative
      humidity of 40% and 80%. Interfacial tension at water/air and water/alkane
      interfaces is measured to explain spreading performance. FINDINGS: Catanionic
      solutions can wet hydrophobic substrates nearly as effective as solutions of
      trisiloxane superspreader. The spreading factor reaches 70% of that of
      superspreader for the most effective mixed solution. The spreading slows down
      earlier at high surfactant concentrations. At room humidity (40%) spread area has
      a maximum vs concentration. However, the maximum was not observed at higher
      humidity 80%. Humidity does not affect the short-time spreading rate, but it
      influences considerably the time when spreading slows down. The spreading rate of
      mixed solutions is smaller than that of superspreader despite the same spreading
      exponent alpha=0.5.

PMID- 26301837
TI  - Sunlight-driven photocatalytic degradation of non-steroidal anti-inflammatory
      drug based on TiO2 quantum dots.
AB  - This paper reports the facile synthesis, characterization and solar-light driven
      photocatalytic degradation of TiO2 quantum dots (QDs). The TiO2 QDs were
      synthesized by a facile ultrasonic-assisted hydrothermal process and
      characterized in terms of their structural, morphological, optical and
      photocatalytic properties. The detailed studies confirmed that the prepared QDs
      are well-crystalline, grown in high density and exhibiting good optical
      properties. Further, the prepared QDs were efficiently used as effective
      photocatalyst for the sun-light driven photocatalytic degradation of ketorolac
      tromethamine, a well-known non-steroidal anti-inflammatory drug (NSAID). To
      optimize the photocatalytic degradation conditions, various dose-dependent, pH
      dependent, and initial drug-concentration dependent experiments were performed.
      The detailed solar-light driven photocatalytic experiments revealed that ~99%
      photodegradation of ketorolac tromethamine drug solution (10 mg L(-1)) was
      observed with optimized amount of TiO2 QDs and pH (0.5 g L(-1) and 4.4,
      respectively) under solar-light irradiations. The observed results demonstrate
      that simply synthesized TiO2 QDs can efficiently be used for the solar-light
      driven photocatalytic degradation of harmful drugs and chemicals.

PMID- 26301839
TI  - Diffusiophoretic motion of an isolated charged porous sphere.
AB  - Diffusiophoretic motion, the migration of a colloidal particle in response to an
      externally applied solute concentration gradient, is investigated theoretically
      in this study for an isolated charged porous sphere suspended in an unbounded
      medium of electrolyte solution. The porous sphere is treated as a Brinkman medium
      with a uniformly distributed fixed charge density. The resulted general
      electrokinetic equations adopting the full nonlinear Poisson equation are solved
      numerically with a pseudo-spectral method based on Chebyshev polynomials. In
      particular, the convection contribution of the ion flux is taken into account
      properly as well. Key parameters of electrokinetic interest are examined for
      their respective effect on the particle motion. The particle mobility is much
      smaller in general than the analytical prediction neglecting the convection
      induced double layer polarization effect, which is by far the most important
      factor in determining the porous particle motion. A less charged particle may
      actually move faster than a highly charged one due to this effect. Visual
      demonstration of the polarization is provided. Formation of a separate
      axisymmetric vortex flow is be responsible for the observation that a particle
      may reverse its direction of motion across a threshold permeability. This implies
      that a porous polyelectrolyte (like a protein or a DNA) assuming a random coil
      conformation may tango back and forth as it makes gyrations in diffusiophoretic
      motion. 

PMID- 26301838
TI  - Insights into the synthesis of layered double hydroxide (LDH) nanoparticles: Part
      1. Optimization and controlled synthesis of chloride-intercalated LDH.
AB  - Layered double hydroxide (LDH) nanoparticles have excellent anion-intercalating
      property, and their potential as theranostic nanovectors is high. However,
      understanding of the control of the mean particle size (MPS) and achievement of
      monodispersed particle size distribution (PSD) remains elusive. Herein, with the
      aid of statistical design of experiments on a model system of Cl(-)-intercalated
      (Zn, Al)-LDH, controlled synthesis of single crystalline nanoparticles using the
      coprecipitation method followed by hydrothermal treatment (HT) was achieved in
      three steps. First, a 2(4-1) design enabled the identification of influential
      parameters for MPS (i.e., salt concentration, molar ratio of carbonate to
      aluminum, solution addition rate, and interaction between salt concentration and
      stirring rate) and PSD (i.e., salt concentration and stirring rate), as well as
      the optimum coprecipitation conditions that result in a monodispersed PSD (i.e.,
      low salt concentration and high stirring rate). Second, a preliminary explanation
      of the HT was suggested and the optimum HT conditions for obtaining ideal
      Gaussian PSD with chi-squared (chi(2))<3 were found to be 85 degrees C for 5 h.
      Third, using a central composite design, a quantitative MPS model, expressed in
      terms of the significant factors, was developed and experimentally verified to
      synthesize nearly monodispersed LDH nanoparticles with MPS ~200-500 nm.

PMID- 26301840
TI  - Plasma-Treated Thickness-Controlled Two-Dimensional Black Phosphorus and Its
      Electronic Transport Properties.
AB  - We report the preparation of thickness-controlled few-layer black phosphorus (BP)
      films through the modulated plasma treatment of BP flakes. Not only does the
      plasma treatment control the thickness of the BP film, it also removes the
      chemical degradation of the exposed oxidized BP surface, which results in
      enhanced field-effect transistor (FET) performance. Our fabricated BP FETs were
      passivated with poly(methyl methacrylate) (PMMA) immediately after the plasma
      etching process. With these techniques, a high field-effect mobility was
      achieved, 1150 cm(2)/(V s), with an Ion/Ioff ratio of ~10(5) at room temperature.
      Furthermore, a fabricated FET with plasma-treated few-layer BP that was
      passivated with PMMA was found to retain its I-V characteristics and thus to
      exhibit excellent environmental stability over several weeks. 

PMID- 26301841
TI  - Oscope identifies oscillatory genes in unsynchronized single-cell RNA-seq
      experiments.
AB  - Oscillatory gene expression is fundamental to development, but technologies for
      monitoring expression oscillations are limited. We have developed a statistical
      approach called Oscope to identify and characterize the transcriptional dynamics
      of oscillating genes in single-cell RNA-seq data from an unsynchronized cell
      population. Applying Oscope to a number of data sets, we demonstrated its utility
      and also identified a potential artifact in the Fluidigm C1 platform. 

PMID- 26301842
TI  - Trajectories of cell-cycle progression from fixed cell populations.
AB  - An accurate dissection of sources of cell-to-cell variability is crucial for
      quantitative biology at the single-cell level but has been challenging for the
      cell cycle. We present Cycler, a robust method that constructs a continuous
      trajectory of cell-cycle progression from images of fixed cells. Cycler handles
      heterogeneous microenvironments and does not require perturbations or genetic
      markers, making it generally applicable to quantifying multiple sources of cell
      to-cell variability in mammalian cells. 

PMID- 26301843
TI  - Predicting effects of noncoding variants with deep learning-based sequence model.
AB  - Identifying functional effects of noncoding variants is a major challenge in
      human genetics. To predict the noncoding-variant effects de novo from sequence,
      we developed a deep learning-based algorithmic framework, DeepSEA
      (http://deepsea.princeton.edu/), that directly learns a regulatory sequence code
      from large-scale chromatin-profiling data, enabling prediction of chromatin
      effects of sequence alterations with single-nucleotide sensitivity. We further
      used this capability to improve prioritization of functional variants including
      expression quantitative trait loci (eQTLs) and disease-associated variants. 

PMID- 26301844
TI  - Word Recognition Variability With Cochlear Implants: "Perceptual Attention"
      Versus "Auditory Sensitivity".
AB  - OBJECTIVES: Cochlear implantation does not automatically result in robust spoken
      language understanding for postlingually deafened adults. Enormous outcome
      variability exists, related to the complexity of understanding spoken language
      through cochlear implants (CIs), which deliver degraded speech representations.
      This investigation examined variability in word recognition as explained by
      "perceptual attention" and "auditory sensitivity" to acoustic cues underlying
      speech perception. DESIGN: Thirty postlingually deafened adults with CIs and 20
      age-matched controls with normal hearing (NH) were tested. Participants underwent
      assessment of word recognition in quiet and perceptual attention (cue-weighting
      strategies) based on labeling tasks for two phonemic contrasts: (1) "cop"-"cob,"
      based on a duration cue (easily accessible through CIs) or a dynamic spectral cue
      (less accessible through CIs), and (2) "sa"-"sha," based on static or dynamic
      spectral cues (both potentially poorly accessible through CIs). Participants were
      also assessed for auditory sensitivity to the speech cues underlying those
      labeling decisions. RESULTS: Word recognition varied widely among CI users (20 to
      96%), but it was generally poorer than for NH participants. Implant users and NH
      controls showed similar perceptual attention and auditory sensitivity to the
      duration cue, while CI users showed poorer attention and sensitivity to all
      spectral cues. Both attention and sensitivity to spectral cues predicted
      variability in word recognition. CONCLUSIONS: For CI users, both perceptual
      attention and auditory sensitivity are important in word recognition. Efforts
      should be made to better represent spectral cues through implants, while also
      facilitating attention to these cues through auditory training.

PMID- 26301845
TI  - Amphiphilic Peptides A6K and V6K Display Distinct Oligomeric Structures and Self
      Assembly Dynamics: A Combined All-Atom and Coarse-Grained Simulation Study.
AB  - Amphiphilic peptides can self-assemble into ordered nanostructures with different
      morphologies. However, the assembly mechanism and the structures of the early
      assemblies prior to nanostructure formation remain elusive. In this study, we
      investigated the oligomeric structures of two amphiphilic heptapeptides A6K and
      V6K by all-atom explicit-solvent replica-exchange molecular dynamics (REMD)
      simulations, and then examined the assembly dynamics of large aggregates by
      coarse-grained (CG) MD simulations. Our 200 ns REMD simulations show that A6K
      peptides predominantly adopt loosely packed disordered coil aggregates, whereas
      V6K peptides mostly assemble into compact beta-sheet-rich conformations,
      consistent with the signal measured experimentally in aqueous solution. Well
      organized beta-sheet-rich conformations, albeit with low population, are also
      populated for V6K octamers, including bilayer beta-sheets and beta-barrels. These
      ordered beta-sheet-rich conformations are observed for the first time for
      amphiphilic peptides. Our 10-MUs CG-MD simulations on 200 peptide chains
      demonstrate that A6K and V6K peptides follow two different self-assembly
      processes, and the former form monolayer lamellas while the latter assemble into
      plate-like assemblies. CG-MD simulations also show that V6K peptides display
      higher assembly capability than A6K, in support of our all-atom REMD simulation
      results. Interpeptide interaction analyses reveal that the marked differences in
      oligomeric structures and assembly dynamics between A6K and V6K result from the
      subtle interplay of competition among hydrophobic, hydrogen-bonding, and
      electrostatic interactions of the two peptides. Our study provides structural and
      mechanistic insights into the initial self-assembly process of A6K and V6K at the
      molecular level. 

PMID- 26301846
TI  - Assessment of volatile organic compounds and particulate matter in a dental
      clinic and health risks to clinic personnel.
AB  - This study was conducted to assess (1) levels of volatile organic compounds
      (VOCs) and particulate matter (PM) in a dental clinic in southern Taiwan and (2)
      dental care personnel's health risks associated with due to chronic exposure to
      VOCs. An automatic, continuous sampling system and a multi-gas monitor were
      employed to quantify the air pollutants, along with environmental comfort
      factors, including temperature, CO2, and relative humidity at six sampling sites
      in the clinic over eight days. Specific VOC compounds were identified and their
      concentrations were quantified. Both non-carcinogenic and carcinogenic VOC
      compounds were assessed based on the US Environmental Protection Agency's
      Principles of Health Risk Assessment in terms of whether those indoor air
      pollutants increased health risks for the full-time dental care professionals at
      the clinic. Increased levels of VOCs were recorded during business hours and
      exceeded limits recommended by the Taiwan Environmental Protection Agency. A
      total of 68 VOC compounds were identified in the study area. Methylene
      methacrylate (2.8 ppm) and acetone (0.176 ppm) were the only two non-carcinogenic
      compounds that posed increased risks for human health, yielding hazard indexes of
      16.4 and 4.1, respectively. None of the carcinogenic compounds increased cancer
      risk. All detected PM10 levels ranged from 20 to 150 MUg/m(3), which met the
      Taiwan EPA and international limits. The average PM10 level during business hours
      was significantly higher than that during non-business hours (P = 0.04). Improved
      ventilation capacity in the air conditioning system was recommended to reduce
      VOCs and PM levels.

PMID- 26301847
TI  - UASB reactor effluent disinfection by ozone and chlorine.
AB  - This research studied the sequential ozone and chlorine process with respect to,
      the inactivation of indicator bacteria and the formation of ozone disinfection
      byproducts in sanitary wastewater effluent. The applied ozone doses were 5, 8 and
      10 mg.O3.L(-1), followed by chlorine doses of 10, 20 and 30 mg.L(-1),
      respectively. After the sequential ozone/chlorine process, the mean reduction in
      chemical oxygen demand ranged from 9 to 37%. Total coliform inactivation ranged
      from 1.59 to 3.73 log10, and E. coli was always <1 CFU 100 mL(-1). Ozonation
      resulted in the formation of aldehydes, which were not significantly impacted by
      the subsequent chlorine dose (P <= 0.05). 

PMID- 26301848
TI  - Effectiveness of ultrasound, UV-C, and photocatalysis on inactivation kinetics of
      Aeromonas hydrophila.
AB  - In this study, bactericidal effects of 24 kHz ultrasound, ultraviolet (UV-C)
      irradiation, and titanium dioxide (TiO2) photocatalyst were studied on
      inactivation of Aeromonas hydrophila, an emerging pathogen listed on the US
      Environmental Protection Agency's (US EPA) candidate contaminant list. Metabolic
      activity (using the AlamarBlue dye) assays were performed to assess the residual
      activity of the microbial cells after the disinfection treatments along with
      culture-based methods. A faster inactivation rate of 1.52 log min(-1) and
      inactivation of 7.62 log10 was observed within 5 min of ultrasound exposure.
      Ultrasound treated cells repaired by 1.4 log10 in contrast to 5.3 log10 repair
      for UV-C treated cells. Ultrasound treatment significantly lowered the
      reactivation of Aeromonas hydrophila in comparison to UV-C- and UV-C-induced
      photocatalysis. Ultrasound appeared to be an effective means of inactivating
      Aeromonas hydrophila and could be used as a potential disinfection method for
      water and wastewater reuse.

PMID- 26301849
TI  - Efficient removal of mercury from aqueous solutions and industrial effluent.
AB  - The objective of this study was to examine the ability of a solid waste produced
      during beneficiation of ornamental rocks to remove mercury (Hg) from an
      industrial effluent and aqueous solutions under various conditions. Batch studies
      have been carried out by observing the effects of pH, concentration of the
      adsorbate, contact time, and so on. Various sorption isotherm models such as
      Langmuir, Freundlich, and Toth have been applied for the adsorbent. Film and
      intraparticle diffusion were both found to be rate-limiting steps. Adsorption was
      properly described by the Freundlich model (capacity constant of 0.3090 (mg g(
      1))(mg L(-1))(-1/n) and adsorption intensity indicator of 2.2939), which
      indicated a favorable sorption and encouraged subsequent studies for treatment of
      Hg-containing industrial effluent. Industrial effluent treatment efficiency
      reached Hg removals greater than 90% by using ornamental rock solid waste (ORSW).
      Besides, desorption studies indicated that the maximum recovery of mercury was
      100 +/- 2% for 1 mol L(-1) HNO3 and 74 +/- 8% for 0.1 mol L(-1) HNO3. The ORSW
      could be reused thrice without significant difference on the Hg removal rate from
      industrial effluent. These findings place ORSW as a promising efficient and low
      cost adsorbent for the removal of Hg from aqueous solutions and industrial
      effluent.

PMID- 26301850
TI  - Comparative evaluation of adsorption kinetics of diclofenac and isoproturon by
      activated carbon.
AB  - Adsorption mechanism of diclofenac and isoproturon onto activated carbon has been
      proposed using Langmuir and Freundlich isotherms. Adsorption capacity and optimum
      adsorption isotherms were predicted by nonlinear regression method. Different
      kinetic equations, pseudo-first-order, pseudo-second-order, intraparticle
      diffusion model and Bangham kinetic model, were applied to study the adsorption
      kinetics of emerging contaminants on activated carbon in two aqueous matrices. 

PMID- 26301851
TI  - Development of wastewater treatment system based on cascade dielectric barrier
      discharge plasma atomizers.
AB  - A novel design for a cascade dielectric barrier discharge (DBD) atomizer was
      applied for treating samples of water containing biological and organic
      contaminants. Several experimental investigations were conducted on artificial
      samples and real sample (digested sludge collected from a wastewater treatment
      plant, WWTP). The artificial water samples were prepared by using different
      concentrations of E. coli for biological samples, whereas acetic acid was used to
      prepare the organic samples. The biological samples were subjected to the plasma
      effect for different treatment periods, and the growth curves of E. coli were
      generated for 24 h after treatment. Moreover, the viable cells were counted after
      each treatment period and the change in E. coli morphology was monitored. The
      results showed that a significant reduction in the viable cell number, by 3
      orders of magnitude, occurred for an artificial biological sample after only 5
      min treatment. The treatment of organic samples for 10 min showed a significant
      reduction in the concentration of acetic acid by 50%. In consequence, treatment
      of real wastewater sample for 10 min resulted in more than 70% reduction in BOD5
      and 30% reduction in COD.

PMID- 26301852
TI  - Mercury in Hazel Bolete Leccinum griseum and soil substratum: Distribution,
      bioconcentration and dietary exposure.
AB  - This study aimed to examine the accumulation and distribution of total mercury
      (Hg) in fruiting bodies of edible wild-grown mushroom Hazel Bolete Leccinum
      griseum (Quel.) Singer, collected from six spatially distantly distributed places
      across Poland and to assess the probable dietary intake of the element by
      consumers. Mercury content of fungal and soil samples were determined by cold
      vapour atomic absorption spectroscopy (CV-AAS) with a direct sample thermal
      decomposition coupled with gold wool trap of Hg and its further desorption and
      quantitative measurement at the wavelength of 296 nm. The median values of Hg
      content in caps of L. griseum collected from less-contaminated places (< 0.10 mg
      Hg kg(-1) dry matter in upper 0-10 cm layer of soil substratum) were from 0.23 mg
      kg(-1) dm to 0.43 mg kg(-1) dm. And for more contaminated topsoil (0.15 mg Hg kg(
      1) dry matter), the median in caps was about 1.5 mg kg(-1) dry matter. The
      mushroom L. griseum has potential to accumulate Hg in fruiting bodies, while
      quantities of this element noted in consignments of this species originating from
      the forests with typical background values of Hg in topsoil are low. In the light
      of the published value of PTWI for Hg consumption of fruiting bodies of L.
      griseus emerged in forests of Poland is without health risk for consumers.
      Information on total mercury and methylmercury in Fungi of the genus Leccinum is
      also described briefly.

PMID- 26301853
TI  - Cryptosporidium and Giardia removal by secondary and tertiary wastewater
      treatment.
AB  - Wastewater disposal may be a source of environmental contamination by
      Cryptosporidium and Giardia. This study was conducted to evaluate the prevalence
      of Cryptosporidium oocysts and Giardia cysts in raw and treated wastewater
      effluents. A prevalence of 100% was demonstrated for Giardia cysts in raw
      wastewater, at a concentration range of 10 to 12,225 cysts L(-1), whereas the
      concentration of Cryptosporidium oocysts in raw wastewater was 4 to 125 oocysts
      L(-1). The removal of Giardia cysts by secondary and tertiary treatment processes
      was greater than those observed for Cryptosporidium oocysts and turbidity.
      Cryptosporidium and Giardia were present in 68.5% and 76% of the tertiary
      effluent samples, respectively, at an average concentration of 0.93 cysts L(-1)
      and 9.94 oocysts L(-1). A higher detection limit of Cryptosporidium oocysts in
      wastewater was observed for nested PCR as compared to immune fluorescent assay
      (IFA). C. hominis was found to be the dominant genotype in wastewater effluents
      followed by C. parvum and C. andersoni or C. muris. Giardia was more prevalent
      than Cryptosporidium in the studied community and treatment processes were more
      efficient for the removal of Giardia than Cryptosporidium. Zoonotic genotypes of
      Cryptosporidium were also present in the human community. To assess the public
      health significance of Cryptosporidium oocysts present in tertiary effluent,
      viability (infectivity) needs to be assessed. 

PMID- 26301854
TI  - UV/TiO2 photocatalytic disinfection of carbon-bacteria complexes in activated
      carbon-filtered water: Laboratory and pilot-scale investigation.
AB  - The occurrence of carbon-bacteria complexes in activated carbon filtered water
      has posed a public health problem regarding the biological safety of drinking
      water. The application of combined process of ultraviolet radiation and
      nanostructure titanium dioxide (UV/TiO2) photocatalysis for the disinfection of
      carbon-bacteria complexes were assessed in this study. Results showed that a 1.07
      Lg disinfection rate can be achieved using a UV dose of 20 mJ cm(-2), while the
      optimal UV intensity was 0.01 mW cm(-2). Particle sizes >=8 MUm decreased the
      disinfection efficiency, whereas variation in particle number in activated carbon
      filtered water did not significantly affect the disinfection efficiency.
      Photoreactivation ratio was reduced from 12.07% to 1.69% when the UV dose was
      increased from 5 mJ cm(-2) to 20 mJ cm(-2). Laboratory and on-site pilot-scale
      experiments have demonstrated that UV/TiO2 photocatalytic disinfection technology
      is capable of controlling the risk posed by carbon-bacteria complexes and
      securing drinking water safety.

PMID- 26301855
TI  - Simultaneous stripping recovery of ammonia-nitrogen and precipitation of
      manganese from electrolytic manganese residue by air under calcium oxide assist.
AB  - Leaching tests of electrolytic manganese residue (EMR) indicated that high
      contents of soluble manganese and ammonia-nitrogen posed a high environmental
      risk. This work reports the results of simultaneous stripping recovery of ammonia
      nitrogen and precipitation of manganese by air under calcium oxide assist. The
      ammonia-nitrogen stripping rate increased with the dosage of CaO, the air flow
      rate and the temperature of EMR slurry. Stripped ammonia-nitrogen was absorbed by
      a solution of sulfuric acid and formed soluble (NH4)2SO4 and (NH4)3H(SO4)3. The
      major parameters that effected soluble manganese precipitation were the dosage of
      added CaO and the slurry temperature. Considering these two aspects, the
      efficient operation conditions should be conducted with 8 wt.% added CaO, 60
      degrees C, 800 mL min(-1) air flow rate and 60-min reaction time. Under these
      conditions 99.99% of the soluble manganese was precipitated as Mn3O4, which was
      confirmed by XRD and SEM-EDS analyses. In addition, the stripping rate of ammonia
      nitrogen was 99.73%. Leaching tests showed the leached toxic substances
      concentrations of the treated EMR met the integrated wastewater discharge
      standard of China (GB8978-1996).

PMID- 26301856
TI  - The occurrence and removal of organophosphate ester flame retardants/plasticizers
      in a municipal wastewater treatment plant in the Pearl River Delta, China.
AB  - The occurrence, distribution and main removal pathway of seven widely used
      organophosphate esters (OPs) in a municipal wastewater treatment plant (WWTP)
      located in the Pearl River Delta were investigated. Their daily discharge load
      into the Pearl River via effluent was also estimated. All the target analytes
      were detected in wastewater, suspended particle and dewatered sludge, with tri-n
      butyl phosphate (TBP) and tris(2-butoxyethyl) phosphate (TBEP) as the main
      components. The total concentrations of TBP and TBEP were 21271.8 ng L(-1) and
      4349.4 ng L(-1), 3105.1 ng L(-1) and 494.5 ng L(-1) in influent wastewater and
      final effluent, respectively. These results indicated that non-chlorinated OPs
      were removed efficiently in the WWTP, while chlorinated OPs passed through the
      WWTP unchanged due to their resistance to current wastewater treatment
      technology. Approximate 91.4 g of non-chlorinated OPs and 23.4 g of chlorinated
      OPs per day were discharged into the Pearl River via effluent, 2.4 g of non
      chlorinated OPs and 0.6 g of chlorinated OPs entered the environment following
      sludge disposal.

PMID- 26301857
TI  - Phosphate removal from water by a novel zeolite/lanthanum hydroxide hybrid
      material prepared from coal fly ash.
AB  - This study was undertaken to investigate the effectiveness of the hybrid
      adsorbent, which was synthesized from coal fly ash and was composed of lanthanum
      hydroxide and zeolite (La-ZFA), for phosphate removal from water. Long-term
      repeated adsorption tests for 30 days showed that the maximum removal capacity of
      the material reached 66.09 mg P/g. The fractionation of adsorbed phosphorus
      indicated that phosphate immobilized by La-ZFA was quite irreversible and was
      dominated by HCl-P fraction. It was suggested that the immobilization of
      phosphate was mainly attributed to lanthanum hydroxide and was slightly
      influenced by coexistence of other anions (Cl(-), NO3(-), SO4(2-), and HCO3(-)).
      At a La/P molar ratio between 1.5:1 and 2.0:1, a nearly complete removal (above
      98%) of phosphate could be achieved. La-ZFA also exhibited great performance for
      removing phosphate from lake water (97.29%) as well as the effluent from
      wastewater treatment plant (97.86%), respectively. In addition, based on the
      results of the present study, it was believed that La-ZFA could be a potential
      material for phosphate removal in practical application. 

PMID- 26301858
TI  - Molecular Dynamics and Physical Stability of Coamorphous Ezetimib and Indapamide
      Mixtures.
AB  - Low physical stability is the main reason limiting the widespread use of
      amorphous pharmaceuticals. One approach to overcome this problem is to mix these
      drugs with various excipients. In this study coamorphous drug-drug compositions
      of different molar ratios of ezetimib and indapamid (i.e., EZB 10:1 IDP, EZB 5:1
      IDP, EZB 2:1 IDP, EZB 1:1 IDP and EZB 1:2 IDP) were prepared and investigated
      using differential scanning calorimetry (DSC), broadband dielectric spectroscopy
      (BDS), and X-ray diffraction (XRD). Our studies have shown that the easily
      recrystallizing ezetimib drug can be significantly stabilized in its amorphous
      form by using even a small amount of indapamid (8.8 wt %). DSC experiments
      indicate that the glass transition temperature (Tg) of the tested mixtures
      changes with the drug concentration in accordance with the Gordon-Taylor
      equation. We also investigated the effect of indapamid on the molecular dynamics
      of the ezetimib. As a result it was found that, with increasing indapamid
      content, the molecular mobility of the binary drug-drug system is slowed down.
      Finally, using the XRD technique we examined the long-term physical stability of
      the investigated binary systems stored at room temperature. These measurements
      prove that low-molecular-weight compounds are able to significantly improve the
      physical stability of amorphous APIs. 

PMID- 26301859
TI  - Simple Freeze-Drying Procedure for Producing Nanocellulose Aerogel-Containing,
      High-Performance Air Filters.
AB  - Simple freeze-drying of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-oxidized
      cellulose nanofibril (TOCN) dispersions in water/tert-butyl alcohol (TBA)
      mixtures was conducted to prepare TOCN aerogels as high-performance air filter
      components. The dispersibility of the TOCNs in the water/TBA mixtures, and the
      specific surface area (SSA) of the resulting TOCN aerogels, was investigated as a
      function of the TBA concentration in the mixtures. The TOCNs were homogeneously
      dispersed in the water/TBA mixtures at TBA concentrations up to 40% w/w. The SSAs
      of the TOCN aerogels exceeded 300 m2/g when the TBA concentration in the aqueous
      mixtures was in the range from 20% to 50% w/w. When a commercially available,
      high-efficiency particulate air (HEPA) filter was combined with TOCN/water/TBA
      dispersions prepared using 30% TBA, and the product was freeze-dried, the
      resulting TOCN aerogel-containing filters showed superior filtration properties.
      This was because nanoscale, spider-web-like networks of the TOCNs with large SSAs
      were formed within the filter.

PMID- 26301860
TI  - Security of electronic mental health communication and record-keeping in the
      digital age.
AB  - The mental health field has seen a trend in recent years of the increased use of
      information technology, including mobile phones, tablets, and laptop computers,
      to facilitate clinical treatment delivery to individual patients and for record
      keeping. However, little attention has been paid to ensuring that electronic
      communication with patients is private and secure. This is despite potentially
      deleterious consequences of a data breach, which are reported in the news media
      very frequently in modern times. In this article, we present typical security
      concerns associated with using technology in clinical services or research. We
      also discuss enhancing the privacy and security of electronic communication with
      clinical patients and research participants. We offer practical, easy-to-use
      software application solutions for clinicians and researchers to secure patient
      communication and records. We discuss such issues as using encrypted wireless
      networks, secure e-mail, encrypted messaging and videoconferencing, privacy on
      social networks, and others.

PMID- 26301861
TI  - Peptic Ulcer Disease in Healthcare Workers: A Nationwide Population-Based Cohort
      Study.
AB  - Health care workers (HCWs) in Taiwan have heavy, stressful workloads, are on
      call, and have rotating nightshifts, all of which might contribute to peptic
      ulcer disease (PUD). We wanted to evaluate the PUD risk in HCWs, which is not
      clear. Using Taiwan's National Health Insurance Research Database, we identified
      50,226 physicians, 122,357 nurses, 20,677 pharmacists, and 25,059 other HCWs
      (dieticians, technicians, rehabilitation therapists, and social workers) as the
      study cohort, and randomly selected an identical number of non-HCW patients
      (i.e., general population) as the comparison cohort. Conditional logistical
      regression analysis was used to compare the PUD risk between them. Subgroup
      analysis for physician specialties was also done. Nurses and other HCWs had a
      significantly higher PUD risk than did the general population (odds ratio [OR]:
      1.477; 95% confidence interval [CI]: 1.433-1.521 and OR: 1.328; 95% CI: 1.245
      1.418, respectively); pharmacists had a lower risk (OR: 0.884; 95% CI: 0.828
      0.945); physicians had a nonsignificantly different risk (OR: 1.029; 95% CI:
      0.987-1.072). In the physician specialty subgroup analysis, internal medicine,
      surgery, Ob/Gyn, and family medicine specialists had a higher PUD risk than other
      physicians (OR: 1.579; 95% CI: 1.441-1.731, OR: 1.734; 95% CI: 1.565-1.922, OR:
      1.336; 95% CI: 1.151-1.550, and OR: 1.615; 95% CI: 1.425-1.831, respectively). In
      contrast, emergency physicians had a lower risk (OR: 0.544; 95% CI: 0.359-0.822).
      Heavy workloads, long working hours, workplace stress, rotating nightshifts, and
      coping skills may explain our epidemiological findings of higher risks for PUD in
      some HCWs, which might help us improve our health policies for HCWs. 

PMID- 26301863
TI  - Exploitation of Nanotechnology for the Monitoring of Waterborne Pathogens: State
      of-the-Art and Future Research Priorities.
AB  - Contaminated drinking water is one of the most important environmental
      contributors to the human disease burden. Monitoring of water for the presence of
      pathogens is an essential part of ensuring drinking water safety. In order to
      assess water quality it is essential to have methods available to sample and
      detect the type, level and viability of pathogens in water which are effective,
      cheap, quick, sensitive, and where possible high throughput. Nanotechnology has
      the potential to drastically improve the monitoring of waterborne pathogens when
      compared to conventional approaches. To date, there have been no reviews that
      outline the applications of nanotechnology in this area despite increasing
      exploitation of nanotechnology for this purpose. This review is therefore the
      first overview of the state-of-the-art in the application of nanotechnology to
      waterborne pathogen sampling and detection schemes. Research in this field has
      been centered on the use of engineered nanomaterials. The effectiveness and
      limitations of nanomaterial-based approaches is outlined. A future outlook of the
      advances that are likely to emerge in this area, as well as recommendations for
      areas of further research are provided. 

PMID- 26301862
TI  - Removal of Antimonite (Sb(III)) and Antimonate (Sb(V)) from Aqueous Solution
      Using Carbon Nanofibers That Are Decorated with Zirconium Oxide (ZrO2).
AB  - Zirconium oxide (ZrO2)-carbon nanofibers (ZCN) were fabricated and batch
      experiments were used to determine antimonite (Sb(III)) and antimonate (Sb(V))
      adsorption isotherms and kinetics. ZCN have a maximum Sb(III) and Sb(V)
      adsorption capacity of 70.83 and 57.17 mg/g, respectively. The adsorption process
      between ZCN and Sb was identified to be an exothermic and follows an ion-exchange
      reaction. The application of ZCN was demonstrated using tap water spiked with Sb
      (200 MUg/L). We found that the concentration of Sb was well below the maximum
      contaminant level for drinking water with ZCN dosages of 2 g/L. X-ray
      photoelectron spectroscopy (XPS) revealed that an ionic bond of Zr-O was formed
      with Sb(III) and Sb(V). Based on the density functional theory (DFT)
      calculations, Sb(III) formed Sb-O and O-Zr bonds on the surface of the tetragonal
      ZrO2 (t-ZrO2) (111) plane and monoclinic ZrO2 planes (m-ZrO2) (111) plane when it
      adsorbs. Only an O-Zr bond was formed on the surface of t-ZrO2 (111) plane and m
      ZrO2 (111) plane for Sb(V) adsorption. The adsorption energy (Ead) of Sb(III) and
      Sb(V) onto t-ZrO2 (111) plane were 1.13 and 6.07 eV, which were higher than that
      of m-ZrO2 (0.76 and 3.35 eV, respectively). 

PMID- 26301864
TI  - The effect of an Internet-based intervention designed to reduce HIV/AIDS sexual
      risk among Mexican adolescents.
AB  - INTRODUCTION: The purpose of the study was to evaluate the effect of an Internet
      based intervention to reduce sexual risk behaviors and increase resilience to
      sexual risk behaviors among Mexican adolescents, a key HIV/AIDS risk group.
      METHODOLOGY: The study had a quasi-experimental design with single-stage cluster
      sampling. Participants ages 14-17 were stratified by gender and randomly assigned
      to either receive intervention "Connect" (which included face-to-face and
      Internet-based sessions designed to reduce sexual risk behaviors and increase
      resilience to sexual risk) or control (a general educational video on reducing
      health risks). A total of 9 survey instruments were administered online through
      SurveyMonkey pre- and post-intervention to assess changes in sexual risk and
      protective factors as well as two outcomes of interest: risky sexual behaviors
      and resilience. Pearson correlation assessed instrument reliability while
      multivariable linear regression models assessed two study hypotheses: (1) the
      effect of the intervention on sexual behavior and resilience is mediated by
      adolescent age, gender, and sexual experience and (2) risk and protective factors
      are mediators between the intervention and sexual behavior. RESULTS: The sample
      was composed of 193 adolescents between 14 and 17 years old (n = 96 in the
      control group and n = 97 in the experimental group). Survey instruments were
      reliable. Age was associated with pre-to-post test changes in sexual resilience
      (beta = -6.10, p = .019), which partially mediated the effect of the intervention
      on sexual resilience (beta = 5.70, p = .034). Social support was associated with
      pre-to-post test changes in risky sexual behavior (beta = -0.17, p = .039).
      CONCLUSION: Intervention "Connect" was independently associated with improved
      self-reported resilience to risky sexual behaviors, though not with a reduction
      in those behaviors in multivariate analyses. This is the first Internet-based
      intervention designed to reduce HIV/AIDS sexual risk among Mexican adolescents.

PMID- 26301865
TI  - CCR5 and CXCR3 expression in a case of subcutaneous panniculitis-like T-cell
      lymphoma.

PMID- 26301869
TI  - Role of Ets Proteins in Development, Differentiation, and Function of T-Cell
      Subsets.
AB  - Through positive selection, double-positive cells in the thymus differentiate
      into CD4(+) or CD8(+) T single-positive cells that subsequently develop into
      different types of effective T cells, such as T-helper and cytotoxic T lymphocyte
      cells, that play distinctive roles in the immune system. Development,
      differentiation, and function of thymocytes and CD4(+) and CD8(+) T cells are
      controlled by a multitude of secreted and intracellular factors, ranging from
      cytokine signaling modules to transcription factors and epigenetic modifiers.
      Members of the E26 transformation specific (Ets) family of transcription factors,
      in particular, are potent regulators of these CD4(+) or CD8(+) T-cell processes.
      In this review, we summarize and discuss the functions and underlying mechanisms
      of the Ets family members that have been characterized as involved in these
      processes. Ongoing research of these factors is expected to identify practical
      applications for the Ets family members as novel therapeutic targets for
      inflammation-related diseases. 

PMID- 26301870
TI  - Estimating daily methane production in individual cattle with irregular feed
      intake patterns from short-term methane emission measurements.
AB  - Spot measurements of methane emission rate (n = 18 700) by 24 Angus steers fed
      mixed rations from GrowSafe feeders were made over 3- to 6-min periods by a
      GreenFeed emission monitoring (GEM) unit. The data were analysed to estimate
      daily methane production (DMP; g/day) and derived methane yield (MY; g/kg dry
      matter intake (DMI)). A one-compartment dose model of spot emission rate v. time
      since the preceding meal was compared with the models of Wood (1967) and Dijkstra
      et al. (1997) and the average of spot measures. Fitted values for DMP were
      calculated from the area under the curves. Two methods of relating methane and
      feed intakes were then studied: the classical calculation of MY as DMP/DMI
      (kg/day); and a novel method of estimating DMP from time and size of preceding
      meals using either the data for only the two meals preceding a spot measurement,
      or all meals for 3 days prior. Two approaches were also used to estimate DMP from
      spot measurements: fitting of splines on a 'per-animal per-day' basis and an
      alternate approach of modelling DMP after each feed event by least squares (using
      Solver), summing (for each animal) the contributions from each feed event by best
      fitting a one-compartment model. Time since the preceding meal was of limited
      value in estimating DMP. Even when the meal sizes and time intervals between a
      spot measurement and all feeding events in the previous 72 h were assessed, only
      16.9% of the variance in spot emission rate measured by GEM was explained by this
      feeding information. While using the preceding meal alone gave a biased
      (underestimate) of DMP, allowing for a longer feed history removed this bias. A
      power analysis taking into account the sources of variation in DMP indicated that
      to obtain an estimate of DMP with a 95% confidence interval within 5% of the
      observed 64 days mean of spot measures would require 40 animals measured over 45
      days (two spot measurements per day) or 30 animals measured over 55 days. These
      numbers suggest that spot measurements could be made in association with feed
      efficiency tests made over 70 days. Spot measurements of enteric emissions can be
      used to define DMP but the number of animals and samples are larger than are
      needed when day-long measures are made. 

PMID- 26301866
TI  - Dopaminergic and cholinergic learning mechanisms in nicotine addiction.
AB  - Nicotine addiction drives tobacco use by one billion people worldwide, causing
      nearly six million deaths a year. Nicotine binds to nicotinic acetylcholine
      receptors that are normally activated by the endogenous neurotransmitter
      acetylcholine. The widespread expression of nicotinic receptors throughout the
      nervous system accounts for the diverse physiological effects triggered by
      nicotine. A crucial influence of nicotine is on the synaptic mechanisms
      underlying learning that contribute to the addiction process. Here, we focus on
      the acquisition phase of smoking addiction and review animal model studies on how
      nicotine modifies dopaminergic and cholinergic signaling in key nodes of the
      reinforcement circuitry: ventral tegmental area, nucleus accumbens (NAc),
      amygdala, and hippocampus. Capitalizing on mechanisms that subserve natural
      rewards, nicotine activates midbrain dopamine neurons directly and indirectly,
      and nicotine causes dopamine release in very broad target areas throughout the
      brain, including the NAc, amygdala, and hippocampus. In addition, nicotine
      orchestrates local changes within those target structures, alters the release of
      virtually all major neurotransmitters, and primes the nervous system to the
      influence of other addictive drugs. Hence, understanding how nicotine affects the
      circuitry for synaptic plasticity and learning may aid in developing reasoned
      therapies to treat nicotine addiction. 

PMID- 26301867
TI  - Mechanism of Resistance and Novel Targets Mediating Resistance to EGFR and c-Met
      Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer.
AB  - Tyrosine kinase inhibitors (TKIs) against EGFR and c-Met are initially effective
      when administered individually or in combination to non-small cell lung cancer
      (NSCLC) patients. However, the overall efficacies of TKIs are limited due to the
      development of drug resistance. Therefore, it is important to elucidate
      mechanisms of EGFR and c-Met TKI resistance in order to develop more effective
      therapies. Model NSCLC cell lines H1975 and H2170 were used to study the
      similarities and differences in mechanisms of EGFR/c-Met TKI resistance. H1975
      cells are positive for the T790M EGFR mutation, which confers resistance to
      current EGFR TKI therapies, while H2170 cells are EGFR wild-type. Previously,
      H2170 cells were made resistant to the EGFR TKI erlotinib and the c-Met TKI
      SU11274 by exposure to progressively increasing concentrations of TKIs. In H2170
      and H1975 TKI-resistant cells, key Wnt and mTOR proteins were found to be
      differentially modulated. Wnt signaling transducer, active beta-catenin was
      upregulated in TKI-resistant H2170 cells when compared to parental cells. GATA-6,
      a transcriptional activator of Wnt, was also found to be upregulated in resistant
      H2170 cells. In H2170 erlotinib resistant cells, upregulation of inactive
      GSK3beta (p-GSK3beta) was observed, indicating activation of Wnt and mTOR
      pathways which are otherwise inhibited by its active form. However, in H1975
      cells, Wnt modulators such as active beta-catenin, GATA-6 and p-GSK3beta were
      downregulated. Additional results from MTT cell viability assays demonstrated
      that H1975 cell proliferation was not significantly decreased after Wnt
      inhibition by XAV939, but combination treatment with everolimus (mTOR inhibitor)
      and erlotinib resulted in synergistic cell growth inhibition. Thus, in H2170
      cells and H1975 cells, simultaneous inhibition of key Wnt or mTOR pathway
      proteins in addition to EGFR and c-Met may be a promising strategy for overcoming
      EGFR and c-Met TKI resistance in NSCLC patients. 

PMID- 26301871
TI  - Physiological effects of pH gradients on Escherichia coli during plasmid DNA
      production.
AB  - A two-compartment scale-down system was used to mimic pH heterogeneities that can
      occur in large-scale bioreactors. The system consisted of two interconnected
      stirred tank reactors (STRs) where one of them represented the conditions of the
      bulk of the fluid and the second one the zone of alkali addition for pH control.
      The working volumes ratio of the STRs was set to 20:1 in order to simulate the
      relative sizes of the bulk and alkali addition zones, respectively, in large
      scale bioreactors. Residence times (tR ) in the alkali addition STR of 60, 120,
      180, and 240 s were simulated during batch cultures of an engineered Escherichia
      coli strain that produced plasmid DNA (pDNA). pH gradients of up to 0.9 units,
      between the two compartments, were attained. The kinetic, stoichiometric, and
      pDNA topological changes due to the pH gradients were studied and compared to
      cultures at constant pH of 7.2 and 8.0. As the tR increased, the pDNA and biomass
      yields, as well as pDNA final titer decreased, whereas the accumulation of
      organic acids increased. Furthermore, the transcriptional response of 10 selected
      genes to alkaline stress (pH 8.0) and pH gradients was monitored at different
      stages of the cultures. The selected genes coded for ion transporters, amino
      acids catabolism enzymes, and transcriptional regulators. The transcriptional
      response of genes coding for amino acids catabolism, in terms of relative
      transcription level and stage of maximal expression, was different when the
      alkaline stress was constant or transient. This suggests the activation of
      different mechanisms by E. coli to cope with pH fluctuations compared to constant
      alkaline pH. Moreover, the transcriptional response of genes related to negative
      control of DNA synthesis did not correlate with the lower pDNA yields. This is
      the first study that reports the effects of pH gradients on pDNA production by E.
      coli cultures. The information presented can be useful for the design of better
      bioreactor scale-up strategies.

PMID- 26301868
TI  - Functional electron paramagnetic resonance imaging of ischemic rat heart:
      Monitoring of tissue oxygenation and pH.
AB  - PURPOSE: Electron paramagnetic resonance (EPR) imaging in the spectral-spatial
      domain with application of soluble paramagnetic probes provides an opportunity
      for spatially resolved functional measurements of living objects. The purpose of
      this study was to develop EPR methods for visualization of oxygenation and
      acidosis of ischemic myocardium. METHODS: EPR oxygen measurements were performed
      using isotopically substituted (2) H,(15) N-dicarboxyproxyl. The radical has an
      EPR line width of 320 mG and oxygen-induced line broadening of 0.53 mG/mm Hg,
      providing oxygen sensitivity down to 5 MUM. pH measurements were performed using
      previously developed pH-sensitive imidazoline nitroxide. The radical has an EPR
      spectrum with pH-dependable hyperfine splitting, pK = 6.6, providing pH
      sensitivity of approximately 0.05 U in the physiological range. RESULTS: EPR
      imaging of isolated and perfused rat hearts was performed in the two-dimensional
      + spectral domain. The spatial resolution of the measurements was about 1.4 mm.
      Marked tissue hypoxia was observed in the ischemic area of the heart after
      occlusion of the left anterior descending coronary artery. Tissue oxygenation was
      partly restored upon reperfusion. EPR mapping of myocardial pH indicated acidosis
      of the ischemic area down to pH 6.7-6.8. CONCLUSION: This study demonstrates the
      capability of low-field EPR and the nitroxide spin probes for mapping of
      myocardial oxygenation and pH. The developed approaches might be used for
      noninvasive investigation of microenvironment on living objects. Magn Reson Med
      76:350-358, 2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 26301872
TI  - Quantitative Phylogenomics of Within-Species Mitogenome Variation: Monte Carlo
      and Non-Parametric Analysis of Phylogeographic Structure among Discrete
      Transatlantic Breeding Areas of Harp Seals (Pagophilus groenlandicus).
AB  - Phylogenomic analysis of highly-resolved intraspecific phylogenies obtained from
      complete mitochondrial DNA genomes has had great success in clarifying
      relationships within and among human populations, but has found limited
      application in other wild species. Analytical challenges include assessment of
      random versus non-random phylogeographic distributions, and quantification of
      differences in tree topologies among populations. Harp Seals (Pagophilus
      groenlandicus Erxleben, 1777) have a biogeographic distribution based on four
      discrete trans-Atlantic breeding and whelping populations located on "fast ice"
      attached to land in the White Sea, Greenland Sea, the Labrador ice Front, and
      Southern Gulf of St Lawrence. This East to West distribution provides a set of a
      priori phylogeographic hypotheses. Outstanding biogeographic questions include
      the degree of genetic distinctiveness among these populations, in particular
      between the Greenland Sea and White Sea grounds. We obtained complete coding
      region DNA sequences (15,825 bp) for 53 seals. Each seal has a unique mtDNA
      genome sequence, which differ by 6 ~ 107 substitutions. Six major clades / groups
      are detectable by parsimony, neighbor-joining, and Bayesian methods, all of which
      are found in breeding populations on either side of the Atlantic. The species
      coalescent is at 180 KYA; the most recent clade, which accounts for 66% of the
      diversity, reflects an expansion during the mid-Wisconsinan glaciation 40~60 KYA.
      FST is significant only between the White Sea and Greenland Sea or Ice Front
      populations. Hierarchal AMOVA of 2-, 3-, or 4-island models identifies small but
      significant PhiSC among populations within groups, but not among groups. A novel
      Monte-Carlo simulation indicates that the observed distribution of individuals
      within breeding populations over the phylogenetic tree requires significantly
      fewer dispersal events than random expectation, consistent with island or a
      priori East to West 2- or 3-stepping-stone biogeographic models, but not a simple
      1-step trans-Atlantic model. Plots of the cumulative pairwise sequence difference
      curves among seals in each of the four populations provide continuous proxies for
      phylogenetic diversification within each. Non-parametric Kolmogorov-Smirnov (K-S)
      tests of maximum pairwise differences between these curves indicates that the
      Greenland Sea population has a markedly younger phylogenetic structure than
      either the White Sea population or the two Northwest Atlantic populations, which
      are of intermediate age and homogeneous structure. The Monte Carlo and K-S
      assessments provide sensitive quantitative tests of within-species mitogenomic
      phylogeography. This is the first study to indicate that the White Sea and
      Greenland Sea populations have different population genetic histories. The
      analysis supports the hypothesis that Harp Seals comprises three genetically
      distinguishable breeding populations, in the White Sea, Greenland Sea, and
      Northwest Atlantic. Implications for an ice-dependent species during ongoing
      climate change are discussed.

PMID- 26301873
TI  - Networks of Collaboration among Scientists in a Center for Diabetes Translation
      Research.
AB  - BACKGROUND: Transdisciplinary collaboration is essential in addressing the
      translation gap between scientific discovery and delivery of evidence-based
      interventions to prevent and treat diabetes. We examined patterns of
      collaboration among scientists at the Washington University Center for Diabetes
      Translation Research. METHODS: Members (n = 56) of the Washington University
      Center for Diabetes Translation Research were surveyed about collaboration
      overall and on publications, presentations, and grants; 87.5% responded (n = 49).
      We used traditional and network descriptive statistics and visualization to
      examine the networks and exponential random graph modeling to identify predictors
      of collaboration. RESULTS: The 56 network members represented nine disciplines.
      On average, network members had been affiliated with the center for 3.86 years
      (s.d. = 1.41). The director was by far the most central in all networks. The
      overall and publication networks were the densest, while the overall and grant
      networks were the most centralized. The grant network was the most
      transdisciplinary. The presentation network was the least dense, least
      centralized, and least transdisciplinary. For every year of center affiliation,
      network members were 10% more likely to collaborate (OR: 1.10; 95% CI: 1.00-1.21)
      and 13% more likely to write a paper together (OR: 1.13; 95% CI: 1.02-1.25).
      Network members in the same discipline were over twice as likely to collaborate
      in the overall network (OR: 2.10; 95% CI: 1.40-3.15); however, discipline was not
      associated with collaboration in the other networks. Rank was not associated with
      collaboration in any network. CONCLUSIONS: As transdisciplinary centers become
      more common, it is important to identify structural features, such as a central
      leader and ongoing collaboration over time, associated with scholarly
      productivity and, ultimately, with advancing science and practice.

PMID- 26301874
TI  - The neural development of the biological motion processing system does not rely
      on early visual input.
AB  - Naturally occurring sensory deprivation in humans provides a unique opportunity
      to identify sensitive phases for the development of neuro-cognitive functions.
      Patients who had experienced a transient period of congenital visual deprivation
      due to bilateral dense cataracts (congenital cataract, cc) have shown, after
      visual re-afferentation, deficits in a number of higher visual functions
      including global motion and face processing. By contrast, biological motion (BM)
      perception seemed to be spared. The present study investigated the neural
      correlates of BM processing in a sample of 12 congenital cataract-reversal
      individuals who had underwent visual restoration surgery at the age of a few
      months up to several years. The individual threshold for extracting BM from noise
      was assessed in a behavioral task while event-related potentials (ERPs) were
      recorded in response to point-light displays of a walking man and of a scrambled
      version of the same stimuli. The threshold of the cc group at detecting BM did
      not differ from that of a group of matched controls (mc). In both groups, the N1
      was modulated by BM. These largely unimpaired neural responses to BM stimuli
      together with a lack of behavioral group differences suggest that, in contrast to
      the neural systems for faces the neural systems for BM processing specialize
      independent of early visual input. 

PMID- 26301876
TI  - Correction: Multiple Sparse Representations Classification.

PMID- 26301875
TI  - No effects of 20 Hz-rTMS of the primary motor cortex in vegetative state: A
      randomised, sham-controlled study.
AB  - We assessed the effects of a non-invasive neuromodulatory intervention with
      repetitive transcranial magnetic stimulation (rTMS) of the motor cortex in
      patients with vegetative state (VS) by a randomised, sham-controlled study with a
      cross-over design. Eleven patients classified as being in VS (9 post-anoxic, 2
      post-traumatic, time elapsed from the injury 9-85 months) were included in the
      study. Real or sham 20 Hz rTMS were applied to the left primary motor cortex (M1)
      for 5 consecutive days. Primary outcome measures were changes in the JFK Coma
      Recovery Scale-Revised (CRS-R) scale total score and Clinical Global Impression
      Improvement (CGI-I) scale. Additional measures were EEG changes and impression of
      the patients' relatives using the CGI-I scale. Evaluations were blindly performed
      at baseline, after the first day of treatment, immediately after the end of the 5
      days treatment, 1 week and 1 month later. Slight changes observed in the CRS-R
      and CGI-I scores did not significantly differ between real or sham stimulation
      conditions. EEG was not significantly changed on average, although spots of brain
      reactivity were occasionally found underneath the stimulation point. Findings did
      not provide evidence of therapeutic effect of 20 Hz rTMS of the M1 in chronic VS,
      at least with conventional coils and current safety parameters. Therefore, they
      might be useful to better allocate human and financial resources in future
      trials. 

PMID- 26301877
TI  - Antiquity and geographic distribution of cranial modification among the
      prehistoric groups of Fuego-Patagonia, Chile.
AB  - OBJECTIVES: Nineteenth and twentieth century documents testify that four ethnic
      groups, generally classified as terrestrial hunters or canoe nomads, inhabited
      Fuego-Patagonia. Archaeologically, however, their presence and temporal depth
      remains unknown. This study analyzes the antiquity and geographic distribution of
      cranial modification, a highly visible symbol of social identity, in Fuego
      Patagonia, Chile, to assess whether it expressed ethnic affiliation. MATERIALS
      AND METHODS: A total of 60 adult skulls from Southern Patagonia (n = 32; 53.3%)
      and Tierra del Fuego (n = 28; 46.7%) were examined for age-at-death, sex and
      cranial modification with standard methods. Individuals were further categorized
      as terrestrial (n = 26; 43.3%), marine (n = 21; 35%) or indetermined hunter
      gatherers (n = 13; 21.7%) based on the archaeological site's characteristics,
      geographic location, and isotopic information. RESULTS: Thirty percent (n = 18)
      of the skulls in this study were modified, and most of the modified skulls (n =
      15) presented a tabular-erect shape. No statistically significant differences
      were identified between Fuegians and Patagonians, males or females, or between
      the different types of adaptation and geographic locations. DISCUSSION: Thus,
      this Late Holocene, widely distributed practice, was not a reflection of
      ethnicity, but a material expression of information circulation and the complex
      social relations that these small-size groups had with one another. These results
      suggest that the emergence of modern ethnic identities in the region is a
      historic process that resulted from the interaction of local groups with European
      and Criollos.

PMID- 26301878
TI  - Revisiting Transitional Hypoglycemia: Only Time Will Tell.

PMID- 26301879
TI  - Individual variability of high-sensitivity cardiac troponin levels after aerobic
      exercise is not mediated by exercise mode.
AB  - We compared the response of high-sensitivity cardiac troponin T (hs-cTnT) after
      60 min of swimming, running and cycling in well-trained triathletes. The maximal
      increase in hs-cTnT was similar in all exercise bouts (swimming 453%, cycling
      349% and running 471%) although there was substantial individual variability in
      peak hs-cTnT. The post-exercise kinetics for hs-cTnT was consistent. The change
      in hs-cTnT was correlated between trials. In all trials, hs-cTnT had largely
      returned to baseline levels 24 h post-exercise. In summary, an increase in hs
      cTnT was apparent in all triathletes independent of exercise mode and despite
      variable peak data the consistent kinetics over 24 h post-exercise would suggest
      this represents a physiological phenomenon. 

PMID- 26301881
TI  - Interleukin-17 levels correlate with poor prognosis and vascular endothelial
      growth factor concentration in the serum of patients with non-small cell lung
      cancer.
AB  - OBJECTIVE: The aim of this study was to explore the clinical role of serum
      interleukin-17 in patients with non-small-cell lung cancer (NSCLC). MATERIALS AND
      METHOD: IL-17 expression and microvessel density (MVD) were measured via
      immunohistochemistry in 58 NSCLC tissues. Serum IL-17 and VEGF levels in NSCLC
      patients (n = 43) and healthy controls (n = 37) were analyzed via enzyme-linked
      immunosorbent assay. RESULTS: Serum IL-17 was elevated and the levels positively
      correlated with VEGF concentration in NSCLC patients. Multivariate analyses
      revealed that serum IL-17 levels were an independent prognostic factor in NSCLC.
      CONCLUSION: IL-17 may play a role in NSCLC progression by promoting angiogenesis.

PMID- 26301882
TI  - Inference for reclassification statistics under nested and non-nested models for
      biomarker evaluation.
AB  - The Net Reclassification Improvement (NRI) and the Integrated Discrimination
      Improvement (IDI) are used to evaluate the diagnostic accuracy improvement for
      biomarkers in a wide range of applications. Most applications for these
      reclassification metrics are confined to nested model comparison. We emphasize
      the important extensions of these metrics to the non-nested comparison. Non
      nested models are important in practice, in particular, in high-dimensional data
      analysis and in sophisticated semiparametric modeling. We demonstrate that the
      assessment of accuracy improvement may follow the familiar NRI and IDI
      evaluation. While the statistical properties of the estimators for NRI and IDI
      have been well studied in the nested setting, one cannot always rely on these
      asymptotic results to implement the inference procedure for practical data,
      especially for testing the null hypothesis of no improvement, and these
      properties have not been established for the non-nested setting. We propose a
      generic bootstrap re-sampling procedure for the construction of confidence
      intervals and hypothesis tests. Extensive simulations and real biomedical data
      examples illustrate the applicability of the proposed inference methods for both
      nested and non-nested models. 

PMID- 26301880
TI  - Uric acid correlates to oxidation and inflammation in opposite directions in
      women.
AB  - OBJECTIVE: To evaluate the association of uric acid (UA) levels with a panel of
      markers of oxidative stress and inflammation. METHODS: Plasma UA levels, along
      with a panel of oxidative stress and inflammatory markers, were measured in 755
      Chinese women. RESULTS: Plasma UA levels were inversely associated with urinary
      levels of the oxidative stress marker F2-isoprostanes and positively correlated
      to levels of inflammatory markers, such as C-reactive protein and some
      proinflammatory cytokines (tumor necrosis factor-alpha and interleukin-6) in
      blood as well as prostaglandin E2 metabolites in urine. CONCLUSIONS: Plasma UA
      levels correlate to oxidation and inflammation biomarkers in opposite directions
      in women.

PMID- 26301884
TI  - Candidate biomarkers in heart failure with reduced and preserved ejection
      fraction.
AB  - CONTEXT: Patients presenting with heart failure symptoms are categorized into
      heart failure (HF) with reduced and preserved ejection fraction. OBJECTIVE: Aim
      is to investigate the additional use of candidate biomarkers to characterize
      patients with either sub-type of HF. METHODS: Literature search was conducted in
      the electronic databases MEDLINE and Cochrane Central Register of Controlled
      Trials from inception through November 2014. RESULTS: The results of 47 diseased
      and general population cohorts were included. CONCLUSION: Current studies could
      outline the additional use of candidate biomarkers especially GDF-15, MR-proADM
      and high-sensitive determined troponin, although major outcome studies are still
      missing.

PMID- 26301883
TI  - Low expression of miRNA-224 predicts poor clinical outcome in diffuse large B
      cell lymphoma treated with R-CHOP.
AB  - OBJECTIVE: To investigate the expression and prognostic value of miR-224
      expression in patients with diffuse large B-cell lymphoma (DLBCL) who underwent R
      CHOP. MATERIALS AND METHODS: RT-PCR was used to determine the relative expression
      of miR-224, in 258 DLBCL patients and 40 normal lymphoid tissue specimens.
      RESULTS: MiR-224 expression in DLBCL patients was significantly down-regulated
      compared to that in negative controls (p < 0.05). The 5-year progression-free
      survival and overall survival rates were significantly higher in the high
      expression level group compared to the low-expression level group (p < 0.05).
      CONCLUSIONS: MiR-224 expression level is implicated as a prognostic marker for
      DLBCL patients treated with R-CHOP.

PMID- 26301885
TI  - Effects of adiponectin polymorphisms on the risk of advanced age-related macular
      degeneration.
AB  - OBJECTIVE: To determine the relationships between variants in adiponectin gene
      (ADIPOQ) with advanced forms of age-related macular degeneration (AMD)
      susceptibility. METHODS: A total of 189 advanced AMD patients and 168 controls
      were recruited. Seven tagging single-nucleotide polymorphisms in ADIPOQ were
      genotyped by the SNaPshot method. RESULTS: Alleles or genotypes of rs822396
      distributed significantly differently in advanced AMD patients and controls. The
      minor allele G at rs822396 was associated with an increased risk of advanced AMD
      in a dominant model. Furthermore, haplotype analysis revealed that haplotypes
      AGGACCT and TGACCCC were significantly increased the advanced AMD susceptibility,
      whereas haplotypes AGAACGC, TGAACGT and TGACAGC had protective effects.
      CONCLUSION: ADIPOQ genetic variant rs822396 might affect an individual's
      susceptibility to AMD, making it efficient genetic biomarkers for early detection
      of AMD.

PMID- 26301886
TI  - Evaluation of serum and pleural levels of soluble B7-H4 in lung cancer patients
      with pleural effusion.
AB  - OBJECTIVE: To evaluate the diagnostic value of sB7-H4 and CEA in both serum and
      pleural effusion of lung cancer patients. METHODS: Levels of sB7-H4 and CEA in 90
      patients with malignant pleural effusion due to lung cancer and 58 patients with
      benign pleural effusion were measured by ELISA. RESULTS: The sB7-H4 and CEA
      levels in pleural effusion, serum and their ratio (F/S) were higher in lung
      cancer group than that in benign group (p < 0.01). The diagnostic efficiency of
      sB7-H4 combined CEA was superior to either sB7-H4 or CEA. CONCLUSIONS:
      Measurement of sB7-H4 and CEA might be useful diagnostic value for malignant
      effusion.

PMID- 26301887
TI  - Walkable distances are bioenergetically scaled.
AB  - In perceiving spatial layout, the angular units of visual information are
      transformed into linear units appropriate for specifying size and extent. This
      derivation of linear units from angular ones requires geometry and a ruler.
      Numerous studies suggest that the requisite perceptual rulers are derived from
      the observer's body. In the case of walkable extents, it has been proposed that
      people scale distances to the bioenergetic resources required to traverse the
      extents relative to the bioenergetic resources currently available. The current
      study sought to rigorously test this proposal. Using methods from exercise
      physiology, a host of physiological measures were recorded as participants
      engaged in exercise on 2 occasions: once while provided with a carbohydrate
      supplement and once with a placebo. Distance estimates were made before and after
      exercise on both occasions. As in previous studies, the carbohydrate manipulation
      caused decreased distance estimates relative to the placebo condition. More
      importantly, individual differences in physiological measures that are associated
      with physical fitness predicted distance estimates both before and after the
      experimental manipulations. Results suggest that walkable distances are
      bioenergetically scaled.

PMID- 26301888
TI  - Enucleation after Embolization of Liver Failure-Causing Giant Liver Hemangioma.
AB  - BACKGROUND: Hepatic hemangioma is a congenital tumor of the mesenchymal tissues
      of the liver. While typically benign, these tumors can occasionally grow to
      sufficient size to cause a number of symptoms, including pain, severe hepatic
      dysfunction, or, rarely, consumptive coagulopathy. In such instances, surgical
      treatment may be warranted. CASE REPORT: We present a case of a symptomatic giant
      hepatic hemangioma in an elderly patient who presented with impending liver
      failure. She was successfully treated with a combination of surgical enucleation
      and liver resection after preoperative arterial embolization. We also provide a
      brief discussion of current treatment options for giant hepatic hemangiomas.
      CONCLUSIONS: Early referral to experienced surgical centers before the onset of
      dire complications such as severe hepatic dysfunction and liver failure is
      recommended.

PMID- 26301889
TI  - Identifying Natural Alignments Between Ambulatory Surgery Centers and Local
      Health Systems: Building Broader Communities of Surgical Care.
AB  - OBJECTIVE: To develop and compare methods for identifying natural alignments
      between ambulatory surgery centers (ASCs) and hospitals that anchor local health
      systems. MEASURES: Using all-payer data from Florida's State Ambulatory Surgery
      and Inpatient Databases (2005-2009), we developed 3 methods for identifying
      alignments between ASCS and hospitals. The first, a geographic proximity
      approach, used spatial data to assign an ASC to its nearest hospital neighbor.
      The second, a predominant affiliation approach, assigned an ASC to the hospital
      with which it shared a plurality of surgeons. The third, a network community
      approach, linked an ASC with a larger group of hospitals held together by
      naturally occurring physician networks. We compared each method in terms of its
      ability to capture meaningful and stable affiliations and its administrative
      simplicity. RESULTS: Although the proximity approach was simplest to implement
      and produced the most durable alignments, ASC surgeon's loyalty to the assigned
      hospital was low with this method. The predominant affiliation and network
      community approaches performed better and nearly equivalently on these metrics,
      capturing more meaningful affiliations between ASCs and hospitals. However, the
      latter's alignments were least durable, and it was complex to administer.
      CONCLUSIONS: We describe 3 methods for identifying natural alignments between
      ASCs and hospitals, each with strengths and weaknesses. These methods will help
      health system managers identify ASCs with which to partner. Moreover, health
      services researchers and policy analysts can use them to study broader
      communities of surgical care.

PMID- 26301890
TI  - Factors that Determine Zeolite Stability in Hot Liquid Water.
AB  - The susceptibility of zeolites to hot liquid water may hamper their full
      utilization in aqueous phase processes, such as those involved in biomass
      conversion and upgrading reactions. Interactions of zeolites with water strongly
      depend on the presence of hydrophilic moieties including Bronsted acid sites
      (BAS), extraframework cations, and silanol defects, which facilitate wetting of
      the surface. However, it is not clear which of these moieties are responsible for
      the susceptibility of zeolites to liquid water. Previous studies have offered
      contradictory explanations because the role of each of these characteristics has
      not been investigated independently. In this work, a systematic comparison has
      been attempted by relating crystallinity losses to the variation of each of the
      five zeolite characteristics that may influence their stability in liquid water,
      including number of BAS, Si-O-Si bonds, framework type, silanol defects, and
      extraframework Al. In this study, we have systematically monitored the
      crystallinity changes of a series of HY, H-ZSM-5, and H-beta zeolite samples with
      varying Si/Al ratio, density of BAS, zeolite structure, and density of silanol
      defects upon exposure to liquid water at 200  degrees C. The results of this
      comparison unambiguously indicate that the density of silanol defects plays the
      most crucial role in determining susceptibility of zeolites to hot liquid water.
      By functionalizing the silanol defects with organosilanes, the hydrophobicity of
      defective zeolite is increased and the tolerance to hot liquid water is
      significantly enhanced. 

PMID- 26301892
TI  - Expeditious Synthesis of 2-Phenylquinazolin-4-amines via a Fe/Cu Relay-Catalyzed
      Domino Strategy.
AB  - A highly efficient Fe/Cu relay-catalyzed domino protocol has been developed for
      the synthesis of 2-phenylquinazolin-4-amines from commercially available ortho
      halogenated benzonitriles, aldehydes, and sodium azide. This elegant domino
      process involved consecutive iron-mediated [3 + 2] cycloaddition, copper
      catalyzed SNAr, reduction, cyclization, oxidation, and copper-catalyzed
      denitrogenation sequences. The formed structure is the privileged core in drugs
      and bioactive molecules. 

PMID- 26301891
TI  - MITF is a critical regulator of the carcinoembryonic antigen-related cell
      adhesion molecule 1 (CEACAM1) in malignant melanoma.
AB  - The multifunctional Ig-like carcinoembryonic antigen-related cell adhesion
      molecule 1 (CEACAM1) is neo-expressed in the majority of malignant melanoma
      lesions. CEACAM1 acts as a driver of tumor cell invasion, and its expression
      correlates with poor patient prognosis. Despite its importance in melanoma
      progression, how CEACAM1 expression is regulated is largely unknown. Here, we
      show that CEACAM1 expression in melanoma cell lines and melanoma tissue strongly
      correlates with that of the microphthalmia-associated transcription factor
      (MITF), a key regulator of melanoma proliferation and invasiveness. MITF is
      revealed as a direct and positive regulator for CEACAM1 expression via binding to
      an M-box motif located in the CEACAM1 promoter. Taken together, our study
      provides novel insights into the regulation of CEACAM1 expression and suggests an
      MITF-CEACAM1 axis as a potential determinant of melanoma progression. 

PMID- 26301894
TI  - Recombinant Buckwheat Trypsin Inhibitor Induces Mitophagy by Directly Targeting
      Mitochondria and Causes Mitochondrial Dysfunction in Hep G2 Cells.
AB  - Mitochondria are essential targets for cancer chemotherapy and other disease
      treatments. Recombinant buckwheat trypsin inhibitor (rBTI), a member of the
      potato type I proteinase inhibitor family, was derived from tartary buckwheat
      extracts. Our results showed that rBTI directly targeted mitochondria and induced
      mitochondrial fragmentation and mitophagy. This occurs through enhanced
      depolarization of the mitochondrial membrane potential, increasing reactive
      oxygen species (ROS) generation associated with the rise of the superoxide
      dismutase and catalase activity and glutathione peroxidase (GSH) content, and
      changes in the GSH/oxidized glutathione ratio. Mild and transient ROS induced by
      rBTI were shown to be important signaling molecules required to induce Hep G2
      mitophagy to remove dysfunctional mitochondria. Furthermore, rBTI could directly
      induce mitochondrial fragmentation. It was also noted that rBTI highly increased
      colocalization of mitochondria in treated cells compared to nontreated cells. Tom
      20, a subunit of the translocase of the mitochondrial outer membrane complex
      responsible for recognizing mitochondrial presequences, may be the direct target
      of rBTI. 

PMID- 26301895
TI  - Synthesis of Functionalized Perfluorinated Porphyrins for Improved Spin
      Switching.
AB  - We have established a method to synthesize perfluorinated meso-phenylporphyrins
      with one phenyl group bearing a substituent in the ortho position. These novel
      electron-deficient porphyrins are interesting for model enzymes, catalysis,
      photodynamic therapy, and electron transfer. The key step is the synthesis of an
      iodine-substituted porphyrin and its Suzuki cross coupling with boronic acid
      derivatives. We applied the novel strategy to synthesize a highly electron
      deficient, azopyridine-substituted Ni-porphyrin that undergoes an improved ligand
      driven coordination-induced spin-state switch. 

PMID- 26301893
TI  - Treatment of moderate and severe adult chronic atopic dermatitis with narrow-band
      UVB and the combination of narrow-band UVB/UVA phototherapy.
AB  - The phototherapy is a safe and effective technique for the treatment of adult
      patients with atopic dermatitis (AD). The treatment of chronic forms of the
      disease is most often done with narrow-band UVB (NB-UVB). There also exist
      effective phototherapy options against the AD. The aim of this study was to asses
      if the combination of NB-UVB with UVA was more effective than the treatment with
      only NB-UVB against adult chronic AD. We carried out a prospective and
      observational study. Adult patients with chronic AD with more than 50% of the
      total body surface area affected (TBSA) were included. The affected TBSA was
      calculated using the so-called "rule of nines." Patients with a clearance rate
      >75% of the initial affected TBSA or complete clearance rate were considered as
      complete response (CR). An analogue scale from 0 to 10 was used to measure the
      improvement grade of the pruritus. The treatments were repeated three times a
      week. The initial doses of NB-UVB and UVA were determined by patient's phototype.
      The treatments were performed using a phototherapy booth (UV7002, Walmann,
      Villingen-Schwenningen, Germany((r)) ) with TL01 and UVA fluorescent lamps.
      Statistical analysis was performed with SPSS((r)) (IBM, New York, NY) for Windows
      21.0. A total of 26 patients with adult chronic AD were included in the study, 16
      patients were treated with UVB-BE and 10 patients with the combined treatment
      option NB-UVB/UVA. The mean value of cumulative doses and the mean number of
      performed treatments were similar between both groups of patients (p > 0.05). The
      mean value of duration of response was significantly higher in the patients
      treated only with NB-UVB, 101 versus 6.8 months (p >= 0.05). No differences were
      observed for the patients that showed complete response (p = 0.42) and in the
      analogue scale of pruritus (p > 0.005). In our study, the patients treated with
      the combination of NB-UVB and UVA were similar to the patient that were only
      treated with NB-UVB e. Further prospective and controlled studies have to be
      performed in order to determine the dosing regimens of phototherapy in adult
      patients with AD. 

PMID- 26301896
TI  - Preface.

PMID- 26301897
TI  - Differentiating phosphates by an Mg(2+) complex of the conjugate of calix[4]arene
      via the formation of ternary species and causing changes in the aggregation:
      spectroscopy, microscopy, and computational modeling.
AB  - A phenylene diimine capped conjugate of 1,3-calix[4]arene (L) was synthesized and
      characterized, and its Mg(2+) complex has been isolated and characterized. The
      chemo sensing ensemble of Mg(2+) bound L provides distinguishable features of
      response toward phosphates, viz., HPO4(2-), P2O7(4-), and AMP(2-) (Set A) and
      H2PO4(-), ATP(2-), and ADP(2-) (Set B). While the Set A shows the formation of
      ternary complex, the Set B does not exhibit any intermediate complex, but both
      show the release of Mg(2+) and L at different equivalents. The structures of {L +
      Mg(2+)} and its phosphate bound ternary complexes have been established by
      computational calculations, and the corresponding results agree well with the
      experimental ones. The microscopy studies show an aggregation-disaggregation
      phenomenon in the presence of different equivalents of phosphates in both of the
      sets. Using the fluorescence data, an INHIBIT logic gate has been built. 

PMID- 26301898
TI  - Lipidic nanovesicles stabilize suspensions of metal oxide nanoparticles.
AB  - We have studied the effect of adding lipid nanovesicles (liposomes) on the
      aggregation of commercial titanium oxide (TiO2), zinc oxide (ZnO), or cerium
      oxide (CeO2) nanoparticles (NPs) suspensions in Hepes buffer. Liposomes were
      prepared with pure phospholipids or mixtures of phospholipids and/or cholesterol.
      Changes in turbidity were recorded as a function of time, either of metal
      nanoparticles alone, or for a mixture of nanoparticles and lipidic nanovesicles.
      Lipid nanovesicles markedly decrease the NPs tendency to sediment irrespective of
      size or lipid compositions, thus keeping the metal oxide NPs in suspension. Cryo
      electron microscopy, fluorescence anisotropy of TMA-DPH and general polarization
      of laurdan failed to reveal any major effect of the NPs on the lipid bilayer
      structure or phase state of the lipids. The above data may help in developing
      studies of the interaction of inhaled particles with lung surfactant lipids and
      alveolar macrophages. 

PMID- 26301899
TI  - REDD1 Is Essential for Optimal T Cell Proliferation and Survival.
AB  - REDD1 is a highly conserved stress response protein that is upregulated following
      many types of cellular stress, including hypoxia, DNA damage, energy stress, ER
      stress, and nutrient deprivation. Recently, REDD1 was shown to be involved in
      dexamethasone induced autophagy in murine thymocytes. However, we know little of
      REDD1's function in mature T cells. Here we show for the first time that REDD1 is
      upregulated following T cell stimulation with PHA or CD3/CD28 beads. REDD1
      knockout T cells exhibit a defect in proliferation and cell survival, although
      markers of activation appear normal. These findings demonstrate a previously
      unappreciated role for REDD1 in T cell function. 

PMID- 26301900
TI  - Is the Medial Prefrontal Cortex Necessary for Theory of Mind?
AB  - BACKGROUND: Successful social interaction relies on the ability to attribute
      mental states to other people. Previous functional neuroimaging studies have
      shown that this process, described as Theory of Mind (ToM) or mentalization, is
      reliably associated with activation of the medial prefrontal cortex (mPFC).
      However, this study presents a novel and surprising finding that provides new
      insight into the role of the mPFC in mentalization tasks. METHODOLOGY/PRINCIPAL
      FINDINGS: Twenty healthy individuals were recruited from a wide range of ages and
      social backgrounds. Participants underwent functional magnetic resonance imaging
      (fMRI) while viewing a well-established ToM visual paradigm involving moving
      triangles. Functional MRI data were analyzed using a classical general linear
      model. No activation was detected in the medial prefrontal cortex (mPFC) during
      movement patterns that typically elicit ToM. However, increased activity was
      observed in the right middle occipital gyrus, right temporoparietal junction
      (TPJ), left middle occipital gyrus and right inferior frontal gyrus. No
      correlation was found between participants' age and BOLD response.
      CONCLUSIONS/SIGNIFICANCE: In contrast with previous neuroimaging research, our
      findings support the notion that mPFC function is not critical for reasoning
      about the mental states of others; furthermore, our data indicate that the right
      TPJ and right inferior frontal gyrus are able to perform mentalization without
      any contributions from the mPFC.

PMID- 26301901
TI  - Characterization and manipulation of individual defects in insulating hexagonal
      boron nitride using scanning tunnelling microscopy.
AB  - Defects play a key role in determining the properties and technological
      applications of nanoscale materials and, because they tend to be highly
      localized, characterizing them at the single-defect level is of particular
      importance. Scanning tunnelling microscopy has long been used to image the
      electronic structure of individual point defects in conductors, semiconductors
      and ultrathin films, but such single-defect electronic characterization remains
      an elusive goal for intrinsic bulk insulators. Here, we show that individual
      native defects in an intrinsic bulk hexagonal boron nitride insulator can be
      characterized and manipulated using a scanning tunnelling microscope. This would
      typically be impossible due to the lack of a conducting drain path for electrical
      current. We overcome this problem by using a graphene/boron nitride
      heterostructure, which exploits the atomically thin nature of graphene to allow
      the visualization of defect phenomena in the underlying bulk boron nitride. We
      observe three different defect structures that we attribute to defects within the
      bulk insulating boron nitride. Using scanning tunnelling spectroscopy we obtain
      charge and energy-level information for these boron nitride defect structures. We
      also show that it is possible to manipulate the defects through voltage pulses
      applied to the scanning tunnelling microscope tip. 

PMID- 26301902
TI  - Highly efficient large-area colourless luminescent solar concentrators using
      heavy-metal-free colloidal quantum dots.
AB  - Luminescent solar concentrators serving as semitransparent photovoltaic windows
      could become an important element in net zero energy consumption buildings of the
      future. Colloidal quantum dots are promising materials for luminescent solar
      concentrators as they can be engineered to provide the large Stokes shift
      necessary for suppressing reabsorption losses in large-area devices. Existing
      Stokes-shift-engineered quantum dots allow for only partial coverage of the solar
      spectrum, which limits their light-harvesting ability and leads to colouring of
      the luminescent solar concentrators, complicating their use in architecture.
      Here, we use quantum dots of ternary I-III-VI2 semiconductors to realize the
      first large-area quantum dot-luminescent solar concentrators free of toxic
      elements, with reduced reabsorption and extended coverage of the solar spectrum.
      By incorporating CuInSexS2-x quantum dots into photo-polymerized poly(lauryl
      methacrylate), we obtain freestanding, colourless slabs that introduce no
      distortion to perceived colours and are thus well suited for the realization of
      photovoltaic windows. Thanks to the suppressed reabsorption and high emission
      efficiencies of the quantum dots, we achieve an optical power efficiency of 3.2%.
      Ultrafast spectroscopy studies suggest that the Stokes-shifted emission involves
      a conduction-band electron and a hole residing in an intragap state associated
      with a native defect. 

PMID- 26301903
TI  - Strain engineering Dirac surface states in heteroepitaxial topological
      crystalline insulator thin films.
AB  - The unique crystalline protection of the surface states in topological
      crystalline insulators has led to a series of predictions of strain-generated
      phenomena, from the appearance of pseudo-magnetic fields and helical flat bands
      to the tunability of Dirac surface states by strain that may be used to construct
      'straintronic' nanoswitches. However, the practical realization of this exotic
      phenomenology via strain engineering is experimentally challenging and is yet to
      be achieved. Here, we have designed an experiment to not only generate and
      measure strain locally, but also to directly measure the resulting effects on
      Dirac surface states. We grew heteroepitaxial thin films of topological
      crystalline insulator SnTe in situ and measured them using high-resolution
      scanning tunnelling microscopy to determine picoscale changes in the atomic
      positions, which reveal regions of both tensile and compressive strain.
      Simultaneous Fourier-transform scanning tunnelling spectroscopy was then used to
      determine the effects of strain on the Dirac electrons. We find that strain
      continuously tunes the momentum space position of the Dirac points, consistent
      with theoretical predictions. Our work demonstrates the fundamental mechanism
      necessary for using topological crystalline insulators in strain-based
      applications. 

PMID- 26301904
TI  - An atomically thin matter-wave beamsplitter.
AB  - Matter-wave interferometry has become an essential tool in studies on the
      foundations of quantum physics and for precision measurements. Mechanical
      gratings have played an important role as coherent beamsplitters for atoms,
      molecules and clusters, because the basic diffraction mechanism is the same for
      all particles. However, polarizable objects may experience van der Waals shifts
      when they pass the grating walls, and the undesired dephasing may prevent
      interferometry with massive objects. Here, we explore how to minimize this
      perturbation by reducing the thickness of the diffraction mask to its ultimate
      physical limit, that is, the thickness of a single atom. We have fabricated
      diffraction masks in single-layer and bilayer graphene as well as in a 1 nm thin
      carbonaceous biphenyl membrane. We identify conditions to transform an array of
      single-layer graphene nanoribbons into a grating of carbon nanoscrolls. We show
      that all these ultrathin nanomasks can be used for high-contrast quantum
      diffraction of massive molecules. They can be seen as a nanomechanical answer to
      the question debated by Bohr and Einstein of whether a softly suspended double
      slit would destroy quantum interference. In agreement with Bohr's reasoning we
      show that quantum coherence prevails, even in the limit of atomically thin
      gratings.

PMID- 26301905
TI  - Deficits in visual short-term memory binding in children at risk of non-verbal
      learning disabilities.
AB  - It has been hypothesized that learning disabled children meet short-term memory
      (STM) problems especially when they must bind different types of information,
      however the hypothesis has not been systematically tested. This study assessed
      visual STM for shapes and colors and the binding of shapes and colors, comparing
      a group of children (aged between 8 and 10 years) at risk of non-verbal learning
      disabilities (NLD) with a control group of children matched for general verbal
      abilities, age, gender, and socioeconomic level. Results revealed that groups did
      not differ in retention of either shapes or colors, but children at risk of NLD
      were poorer than controls in memory for shape-color bindings. 

PMID- 26301906
TI  - Phonological memory and word learning deficits in children with specific language
      impairment: A role for perceptual context?
AB  - BACKGROUND: Sensitivity to perceptual context (anchoring) has been suggested to
      contribute to the development of both oral- and written-language skills, but
      studies of this idea in children have been rare. AIMS: To determine whether
      deficient anchoring contributes to the phonological memory and word learning
      deficits of children with specific language impairment (SLI). METHODS AND
      PROCEDURES: 84 preschool children with and without SLI participated in the study.
      Anchoring to repeated items was evaluated in two tasks - a phonological memory
      task and a pseudo-word learning task. OUTCOMES AND RESULTS: Compared to children
      with typical development, children with SLI had poorer phonological memory spans
      and learned fewer words during the word learning task. In both tasks the poorer
      performance of children with SLI reflected a smaller effect of anchoring that was
      manifested in a smaller effect of item repetition on performance. Furthermore,
      across the entire sample anchoring was significantly correlated with performance
      in vocabulary and grammar tasks. CONCLUSIONS AND IMPLICATIONS: These findings are
      consistent with the hypothesis that anchoring contributes to language skills and
      that children with SLI have impaired anchoring, although further studies are
      required to determine the role of anchoring in language development.

PMID- 26301907
TI  - Printable Nanophotonic Devices via Holographic Laser Ablation.
AB  - Holography plays a significant role in applications such as data storage, light
      trapping, security, and biosensors. However, conventional fabrication methods
      remain time-consuming, costly, and complex, limiting the fabrication of holograms
      and their extensive use. Here, we demonstrate a single-pulse laser ablation
      technique to write parallel surface gratings and Fresnel zone plates. We utilized
      a 6 ns high-energy green laser pulse to form interference patterns to record a
      surface grating with 820 nm periodicity and asymmetric zone plate holograms on
      4.5 nm gold-coated substrates. The holographic recording process was completed
      within seconds. The optical characteristics of the interference patterns have
      been computationally modeled, and well-ordered polychromatic diffraction was
      observed from the fabricated holograms. The zone plate showed a significant
      diffraction angle of 32 degrees  from the normal incident for the focal point.
      The nanosecond laser interference ablation for rapid hologram fabrication holds
      great potential in a vast range of optical devices. 

PMID- 26301908
TI  - Theoretical motivations for investigating the neural correlates of consciousness.
AB  - I review the major contenders for the neural correlates of visual awareness.
      Different views of the neural correlates turn out to support different theories,
      such as the global workspace theory, local visual processing theories, and the
      higher-order representation theory. Therefore, studying the neural correlates of
      consciousness may prove useful to theoretical development, although arbitrating
      between different interpretations of the neural results may involve conceptual
      issues as well. WIREs Cogn Sci 2011 2 1-7 DOI: 10.1002/wcs.93 For further
      resources related to this article, please visit the WIREs website. 

PMID- 26301909
TI  - Bayesian learning theory applied to human cognition.
AB  - Probabilistic models based on Bayes' rule are an increasingly popular approach to
      understanding human cognition. Bayesian models allow immense representational
      latitude and complexity. Because they use normative Bayesian mathematics to
      process those representations, they define optimal performance on a given task.
      This article focuses on key mechanisms of Bayesian information processing, and
      provides numerous examples illustrating Bayesian approaches to the study of human
      cognition. We start by providing an overview of Bayesian modeling and Bayesian
      networks. We then describe three types of information processing operations
      inference, parameter learning, and structure learning-in both Bayesian networks
      and human cognition. This is followed by a discussion of the important roles of
      prior knowledge and of active learning. We conclude by outlining some challenges
      for Bayesian models of human cognition that will need to be addressed by future
      research. WIREs Cogn Sci 2011 2 8-21 DOI: 10.1002/wcs.80 For further resources
      related to this article, please visit the WIREs website. 

PMID- 26301910
TI  - Mirror systems.
AB  - Mirror neurons are a class of visuomotor neurons, discovered in the monkey
      premotor cortex and in an anatomically connected area of the inferior parietal
      lobule, that activate both during action execution and action observation. They
      constitute a circuit dedicated to match actions made by others with the internal
      motor representations of the observer. It has been proposed that this matching
      system enables individuals to understand others' behavior and motor intentions.
      Here we will describe the main features of mirror neurons in monkeys. Then we
      will present evidence of the presence of a mirror system in humans and of its
      involvement in several social-cognitive functions, such as imitation, intention,
      and emotion understanding. This system may have several implications at a
      cognitive level and could be linked to specific social deficits in humans such as
      autism. Recent investigations addressed the issue of the plasticity of the mirror
      neuron system in both monkeys and humans, suggesting also their possible use in
      rehabilitation. WIREs Cogn Sci 2011 2 22-38 DOI: 10.1002/wcs.89 For further
      resources related to this article, please visit the WIREs website. 

PMID- 26301911
TI  - From thinking too little to thinking too much: a continuum of decision making.
AB  - Due to the sheer number and variety of decisions that people make in their
      everyday lives-from choosing yogurts to choosing religions to choosing spouses
      research in judgment and decision making has taken many forms. We suggest,
      however, that much of this research has been conducted under two broad rubrics:
      The study of thinking too little (as with the literature on heuristics and
      biases), and the study of thinking too much (as with the literature on decision
      analysis). In this review, we focus on the different types of decision errors
      that result from both modes of thought. For thinking too little, we discuss
      research exploring the ways in which habits can lead people to make suboptimal
      decisions; for thinking too much, we discuss research documenting the ways in
      which careful consideration of attributes, and careful consideration of options,
      can do the same. We end by suggesting that decision makers may do well, when
      making any decision, to consider whether they are facing a 'thinking too much' or
      'thinking too little' problem and adjust accordingly. WIREs Cogn Sci 2011 2 39-46
      DOI: 10.1002/wcs.90 For further resources related to this article, please visit
      the WIREs website. 

PMID- 26301912
TI  - First language acquisition.
AB  - This article reviews current approaches to first language acquisition, arguing in
      favor of the theory that attributes to the child an innate knowledge of universal
      grammar. Such knowledge can accommodate the systematic nature of children's non
      adult linguistic behaviors. The relationships between performance devices
      (mechanisms for comprehension and production of speech), non-linguistic aspects
      of cognition, and child grammars are also discussed. WIREs Cogn Sci 2011 2 47-54
      DOI: 10.1002/wcs.95 For further resources related to this article, please visit
      the WIREs website. 

PMID- 26301913
TI  - An integrative cognitive neuroscience theory of social reasoning and moral
      judgment.
AB  - Cognitive neuroscience has made considerable progress in understanding the
      involvement of the prefrontal cortex (PFC) in social cognition and moral
      judgment. Accumulating evidence suggests that representations within the lateral
      PFC enable people to orchestrate their thoughts and actions in concert with their
      intentions to support goal-directed social behavior. Despite the pivotal role of
      this region in guiding social interactions, remarkably little is known about the
      functional organization and forms of social knowledge mediated by the lateral
      PFC. Here, we review recent theoretical developments in evolutionary psychology
      and emerging evidence from the social and decision neuroscience literatures
      demonstrating the importance of the lateral PFC for orchestrating behavior on the
      basis of evolutionarily adaptive social norms for obligatory, prohibited, and
      permissible courses of action. WIREs Cogn Sci 2011 2 55-67 DOI: 10.1002/wcs.84
      For further resources related to this article, please visit the WIREs website. 

PMID- 26301914
TI  - People watching: visual, motor, and social processes in the perception of human
      movement.
AB  - Successful social behavior requires the accurate perception and interpretation of
      other peoples' actions. In the last decade, significant progress has been made in
      understanding how the human visual system analyzes bodily motion.
      Neurophysiological studies have identified two neural areas, the superior
      temporal sulcus (STS) and the premotor cortex, which play key roles in the visual
      perception of human movement. Patterns of neural activity in these areas are
      reflective of psychophysical measures of visual sensitivity to human movement.
      Both vary as a function of stimulus orientation and global stimulus structure.
      Human observers and STS responsiveness share some developmental similarities as
      both exhibit sensitivities that become increasingly tuned for upright, human
      movement. Furthermore, the observer's own visual and motor experience with an
      action as well as the social and emotional content of that action influence
      behavioral measures of visual sensitivity and patterns of neural activity in the
      STS and premotor cortex. Finally, dysfunction of motor processes, such as
      hemiplegia, and dysfunction of social processes, such as Autism, systematically
      impact visual sensitivity to human movement. In sum, a convergence of visual,
      motor, and social processes underlies our ability to perceive and interpret the
      actions of other people. WIREs Cogn Sci 2011 2 68-78 DOI: 10.1002/wcs.88 For
      further resources related to this article, please visit the WIREs website. 

PMID- 26301915
TI  - Pretense and imagination.
AB  - Issues of pretense and imagination are of central interest to philosophers,
      psychologists, and researchers in allied fields. In this entry, we provide a
      roadmap of some of the central themes around which discussion has been focused.
      We begin with an overview of pretense, imagination, and the relationship between
      them. We then shift our attention to the four specific topics where the
      disciplines' research programs have intersected or where additional interactions
      could prove mutually beneficial: the psychological underpinnings of performing
      pretense and of recognizing pretense, the cognitive capacities involved in
      imaginative engagement with fictions, and the real-world impact of make-believe.
      In the final section, we discuss more briefly a number of other mental activities
      that arguably involve imagining, including counterfactual reasoning, delusions,
      and dreaming. WIREs Cogn Sci 2011 2 79-94 DOI: 10.1002/wcs.91 For further
      resources related to this article, please visit the WIREs website. 

PMID- 26301917
TI  - Embodiment in early development.
AB  - 'Embodiment' has come to represent the many ways in which the body influences the
      functioning of the brain and cognitive processing. This article on embodiment and
      early development reviews several examples of studies demonstrating embodiment in
      cognitive tasks. Our overall message is that what the body does during cognitive
      processing influences cognition in important ways. This might be especially true
      during early development, before actions are automatized. WIREs Cogn Sci 2011 2
      117-123 DOI: 10.1002/wcs.109 For further resources related to this article,
      please visit the WIREs website. 

PMID- 26301918
TI  - Drowning In The Adult Population: Emergency Department Resuscitation And
      Treatment.
AB  - Drowning is a global problem that affects all populations. The events leading up
      to and the sequelae from a drowning incident vary greatly based on numerous
      factors, but the primary physiologic insult is always hypoxia. This is the
      starting point for all morbidity and mortality, and it must remain the focus of
      treatment. This issue discusses the initial resuscitation and treatment of adult
      drowning patients in the emergency department. Primary focus is placed on the key
      components of pathophysiology that require immediate attention. From there,
      evidence is presented to help guide the management of associated clinical
      concerns such as hypothermia, mechanical ventilation, and traumatic injuries, and
      to help form safe and reasonable disposition plans.

PMID- 26301916
TI  - Animal visual perception.
AB  - Perception processes can be investigated at the physical (concerning the
      stimulation from the environment to the receptors), physiological (the processes
      taking place in the neural system), and psychological (the 'sense' of perception,
      the outcome produced by the physical stimulation and the physiological processes)
      level. The present paper focuses on visual perception, mainly from a
      psychological level of investigation, and revises comparative literature,
      highlighting both similarities and differences in the visual structures and
      functions in different animal classes. For this purpose, the structure of the
      current eyes is described in a comparative perspective, as well as perceptual
      organization and object recognition processes, color perception, three
      dimensional structuring of the image, and motion perception. Finally, the
      literature about comparative susceptibility to various visual illusions will be
      discussed, as illusory perception has been revealed to be a most useful tool to
      unveil the perceptual algorithms shared by the different species. In spite of
      major differences between animal species in the structures in charge of
      perception and in the adaptations to specific ecological niches, experimental
      data presented here will lead to the conclusion that a number of basic perceptual
      principles of organization and functioning are shared between species. WIREs Cogn
      Sci 2011 2 106-116 DOI: 10.1002/wcs.97 For further resources related to this
      article, please visit the WIREs website. 

PMID- 26301920
TI  - Probing into the Supramolecular Driving Force of an Amphiphilic beta-Cyclodextrin
      Dimer in Various Solvents: Host-Guest Recognition or Hydrophilic-Hydrophobic
      Interaction?
AB  - Tuning of the morphology and size of supramolecular self-assemblies is of
      theoretical and practical significance. To date, supramolecular driving forces in
      different solvents remain unclear. In this study, we first synthesized an
      amphiphilic beta-cyclodextrin (beta-CD) dimer that consists of one hydrophobic
      ibuprofen (Ibu) and two hydrophilic beta-CD moieties (i.e., Ibu-CD2). Ibu-CD2
      possesses double supramolecular driving forces, namely, the host-guest
      recognition and hydrophilic-hydrophobic interaction. The host-guest interaction
      of Ibu-CD2 induced the formation of branched supramolecular polymers (SPs) in
      pure water, whereas the hydrophilic-hydrophobic interaction generated spherical
      or irregular micelles in water/organic mixtures. The SP size increased with the
      increase in Ibu-CD2 concentration in pure water. By contrast, the size of
      micelles decreased with the increase in volume ratio of water in mixtures. 

PMID- 26301919
TI  - Viral Genetic Linkage Analysis in the Presence of Missing Data.
AB  - Analyses of viral genetic linkage can provide insight into HIV transmission
      dynamics and the impact of prevention interventions. For example, such analyses
      have the potential to determine whether recently-infected individuals have
      acquired viruses circulating within or outside a given community. In addition,
      they have the potential to identify characteristics of chronically infected
      individuals that make their viruses likely to cluster with others circulating
      within a community. Such clustering can be related to the potential of such
      individuals to contribute to the spread of the virus, either directly through
      transmission to their partners or indirectly through further spread of HIV from
      those partners. Assessment of the extent to which individual (incident or
      prevalent) viruses are clustered within a community will be biased if only a
      subset of subjects are observed, especially if that subset is not representative
      of the entire HIV infected population. To address this concern, we develop a
      multiple imputation framework in which missing sequences are imputed based on a
      model for the diversification of viral genomes. The imputation method decreases
      the bias in clustering that arises from informative missingness. Data from a
      household survey conducted in a village in Botswana are used to illustrate these
      methods. We demonstrate that the multiple imputation approach reduces bias in the
      overall proportion of clustering due to the presence of missing observations. 

PMID- 26301921
TI  - Temperature Effects on Micelle Formation and Particle Charging with Span
      Surfactants in Apolar Media.
AB  - This paper examines the effects of temperature on the micellization and particle
      charging behavior of the Span surfactant series in an apolar environment. The
      critical micelle concentrations of each of six surfactants at five temperatures
      were measured by conductometric techniques. The thermodynamic properties of
      micellization were calculated using Gibbs-Helmholtz analysis. Magnesia particles
      were then dispersed in solutions of these surfactants, and their electrophoretic
      mobilities were measured at three temperatures. Preliminary small-angle neutron
      scattering (SANS) experiments were conducted to measure the size of aggregates
      (referred to as reverse micelles) of three of the surfactants. It was found that
      for all but one of the surfactants the critical micelle concentration (CMC)
      increased by as much as an order of magnitude across a 40  degrees C range of
      temperature. One of the surfactants exhibited a decrease in CMC upon increasing
      temperature, likely due to a decrystallization of the tails upon reverse micelle
      formation. The maximum particle mobilities decreased upon increasing temperature
      due to the increased electrostatic screening by charged reverse micelles at
      higher temperatures. 

PMID- 26301922
TI  - Castor Oil-Based Biodegradable Polyesters.
AB  - This Review compiles the synthesis, physical properties, and biomedical
      applications for the polyesters based on castor oil and ricinoleic acid. Castor
      oil has been known for its medicinal value since ancient times. It contains ~90%
      ricinoleic acid, which enables direct chemical transformation into polyesters
      without interference of other fatty acids. The presence of ricinoleic acid
      (hydroxyl containing fatty acid) enables synthesis of various
      polyester/anhydrides. In addition, castor oil contains a cis-double bond that can
      be hydrogenated, oxidized, halogenated, and polymerized. Castor oil is obtained
      pure in large quantities from natural sources; it is safe and biocompatible. 

PMID- 26301924
TI  - Supertoughened Biobased Poly(lactic acid)-Epoxidized Natural Rubber Thermoplastic
      Vulcanizates: Fabrication, Co-continuous Phase Structure, Interfacial in Situ
      Compatibilization, and Toughening Mechanism.
AB  - In the presence of dicumyl peroxide (DCP), biobased thermoplastic vulcanizates
      (TPVs) composed of poly(lactic acid) (PLA) and epoxidized natural rubber (ENR)
      were prepared through dynamic vulcanization. Interfacial in situ
      compatibilization between PLA and ENR phases was confirmed by Fourier transform
      infrared spectroscopy (FT-IR). A novel "sea-sea" co-continuous phase in the
      PLA/ENR TPVs was observed through scanning electron microscopy (SEM) and differed
      from the typical "sea-island" morphology that cross-linked rubber particles
      dispersed in plastic matrix. A sharp, brittle-ductile transition occurred with 40
      wt % of ENR, showing a significantly improved impact strength of 47 kJ/m(2),
      nearly 15 times that of the neat PLA and 2.6 times that of the simple blend with
      the same PLA/ENR ratio. Gel permeation chromatography (GPC) and dynamic
      mechanical analysis (DMA) results suggested that a certain amount of DCP was
      consumed in the PLA phase, causing a slight cross-linking or branching of PLA
      molecules. the effects of various DCP contents on the impact property were
      investigated. The toughening mechanism under impact testing was researched, and
      the influence factors for toughening were discussed. 

PMID- 26301923
TI  - Effectiveness of three interventions in improving adherence to cervical cancer
      screening.
AB  - In countries where cervical cancer screening programmes are conducted on an
      opportunistic basis, an active search for women at risk should be made to
      increase coverage. The objective of our study was to assess the effectiveness of
      three primary care interventions consisting of providing written, telephone and
      face-to-face information to increase screening participation among women over the
      age of 25 years. A randomized experimental study with only one post-test control
      group was conducted on women aged 25-70 years. A total of 1676 women were
      randomly distributed into four groups and the following interventions were
      implemented: written briefing; telephone briefing; an invitation to attend a
      group meeting and no briefing (control group). The women were evaluated 2 years
      after the intervention. The outcome variable was participation or
      nonparticipation in cervical cancer screening. It proved possible to interview a
      total of 1122 women. Among the groups, homogeneity was tested in terms of
      sociodemographic characteristics and health-related variables. Women who had
      undergone cytological testing in the 2 years preceding evaluation had a lower
      mean age (P<0.001) than women who had not done so (45.5+/-11.0 vs. 48.8+/-13.0
      years). The proportion of women who had participated in screening was as follows:
      35.3% in the written information group [95% confidence interval (CI) 29.8-40.9];
      38.4% in the telephone information group (95% CI 32.5-44.2); 29.3% in the face-to
      face information group (95% CI 22.8-35.7) and 26.1% in the control group (95% CI
      21.2-30.9), with this difference proving statistically significant (P=0.005).
      Logistic regression showed that only the interventions based on written or
      telephone briefing were effective vis-a-vis the control group. In conclusion,
      both written and telephone information can serve to improve women's participation
      in opportunistic cervical cancer screening. Current preventive strategies could
      be optimized by means of simple interventions within the scope of health
      professionals.

PMID- 26301925
TI  - Preparation and Identification of a Single-chain Variable Fragment Antibody
      Against Canine Distemper Virus.
AB  - The variable regions of the heavy chain (VH) and light chain (VL) were amplified
      by RT-PCR from the hybridoma 1N8, which secretes the monoclonal antibody against
      CDV N protein (aa 277-471). The VL and VH amplicons were combined using SOE-PCR
      by a 12 amino acid flexible linker (SSGGGGSGGGGS), which produced the scFv gene
      (named scFv/1N8). After sequence analysis, the scFv/1N8 gene was cloned into the
      prokaryotic expression vector PET32a with a His-tag. The recombinant scFv/1N8
      protein was successfully expressed in recombinant Escherichia coli by IPTG
      induction. Moreover, the binding activity and specificity of the scFv were
      determined by indirect ELISA (His-tag) and competitive ELISA. The recombinant
      scFv/1N8 protein reported here will provide some basis for further antiviral drug
      research based on the scFv molecule. 

PMID- 26301927
TI  - A Versatile Monoclonal Antibody Specific Against Human DAB2IP.
AB  - Human DAB2 interaction protein (DAB2IP) is a member of Ras-GTPase activating
      protein family and functions as a tumor suppressor, implying it could serve as a
      prognostic biomarker in cancers. Here we generated a mouse monoclonal antibody,
      2A4, directed against human DAB2IP. This antibody was identified as IgG1 and
      specifically recognizes DAB2IP in both its native and denatured forms. It will
      serve as a useful and versatile tool for further mechanistic study and
      development of the potential prognostic significance of DAB2IP. 

PMID- 26301926
TI  - Isolation and Characterization of Monoclonal Antibodies Against a Virion Core
      Protein of Orf Virus Strain NA1/11 As Potential Diagnostic Tool for Orf Viruses.
AB  - Orf is caused by the orf virus (ORFV) and is a non-systemic, widespread disease
      afflicting sheep, goats, wild ruminants, and humans. Recent outbreaks in sheep
      and goats in Jilin and other northern Chinese provinces raise concerns about orf
      control in China. Thirty-five hybridoma clones were constructed from splenocytes
      of BALB/c mice immunized with natural orf virus protein. These hybridomas were
      used to produce antibodies targeting ORFV proteins. Immunological
      characterization of these monoclonal antibodies (MAb) showed that the 5F2D8
      hybridoma line produced MAb that can recognize the 100, 70, and 20 kDa bands from
      total viral lysate. This hybridoma was further characterized by
      immunoprecipitation and peptide sequencing. The results indicate that 5F2D8
      specifically recognizes orf virus encoded protein ORFV086, a late expression
      virion core protein that plays important roles in progeny virus particle
      assembly, morphogenesis, and maturity. Further experiments demonstrate that this
      MAb did not react with other viral proteins of ORFV orthopoxviruses, but reacted
      strongly to different field isolates of orf viruses from China. Additionally,
      this anti-ORFV086 MAb possesses ORFV neutralizing capability. Sequence alignments
      and phylogenetic analysis determined that ORFV086 of NA1/11, clustered together
      with NZ2 and IA82, is highly conserved and has structural similarities with the
      Vaccinia virus core protein P4a. As such, this MAb has great potential as a
      diagnostic tool for orf viruses, in the further exploration of orf pathogenesis,
      and in disease control and prevention. 

PMID- 26301928
TI  - A Novel Monoclonal Antibody Against Human DAB2IP.
AB  - DAB2 interactive protein (DAB2IP), also known as ASK1-interacting protein-1
      (AIP1), a novel member of the RasGTPase-activating protein family, plays a key
      role in tumor suppression during cancer progression and is highly expressed in
      vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). To further
      explore its function as a cancer suppressor, in this study, we immunized BALB/c
      mice with synthesized human DAB2IP polypeptide and obtained a novel monoclonal
      antibody (MAb) against human DAB2IP. A stable strain of hybridoma was screened
      and successfully established by the hybridoma technique. The
      immunohistochemistry, immunocytochemistry, and Western blot analysis revealed
      that the MAb was directed against human DAB2IP with high specificity. Therefore,
      this MAb may be a useful tool and facilitate studies on tumorigenesis associated
      with DAB2IP. 

PMID- 26301929
TI  - Generation and Characterization of Murine Monoclonal Antibodies anti-PBP2a of
      Methicillin-resistant Staphylococcus aureus.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant
      bacterium that causes serious infections worldwide. This pathogen is resistant to
      all beta lactam antibiotics due the presence of PBP2a, a transpeptidase enzyme
      that presents very low beta-lactam affinity. Here we report the generation and
      characterization of mouse monoclonal antibodies to PBP2a of MRSA strains. Two
      clones were obtained and characterized by immunoassays (ELISA, avidity index
      determination, and immunoblotting), isotyping, association/dissociation rate
      constants by surface plasmon resonance (SPR), and flow cytometry. Clone 38, which
      showed the best avidity and affinity, bound to PBP2a located on the bacterial
      surface by flow cytometry. Further studies are warranted in order to evaluate if
      these antibodies may help inhibit bacterial growth and be used to treat
      infections by MRSA. 

PMID- 26301930
TI  - Preparation and Preliminary Application of MAdCAM-1 Polyclonal Antibody in Dairy
      Cows with Subclinical Mastitis.
AB  - MAdCAM-1 plays an important role in mediating immune response and inflammation.
      This study aimed to express and purify a fusion protein of MAdCAM-1 in
      prokaryotic cells and to prepare rat anti-bovine MAdCAM-1 polyclonal antibodies.
      Prokaryotic expression vector pGEX-4T-1-MAdCAM-1 and pET-28a-MAdCAM-1 were
      constructed, respectively. The above plasmids were transformed into BL21
      Escherichia coli strain. These recombinant strains were induced by IPTG and
      identified by Western blot analysis and SDS-PAGE. Wistar rats were immunized with
      recombinant protein (pET-28a-MAdCAM-1) emulsified with Freund's adjuvant, and
      antibody titers were measured by indirect ELISA. Antibody titers reached the
      highest value (1:128,000) after the third immunization. Western blot showed that
      rat anti-bovine MAdCAM-1 polyclonal antibody can not only recognize recombinant
      MAdCAM-1 protein expressed in E. coli but also recognizes natural MAdCAM-1
      protein extracted from bovine tissues. However, commercial anti-mouse MAdCAM-1
      monoclonal antibodies did not recognize the recombinant MAdCAM-1 protein or
      natural protein, which indicated no cross-reactivity between bovine MAdCAM-1 and
      mouse MAdCAM-1. Real-time fluorescence quantitative polymerase chain reaction and
      Western blot analysis showed that MAdCAM-1 expression was limited in mammary
      lymphoid nodes of subclinical mastitis in dairy cows. We speculate that MAdCAM-1
      expression is inconsistent in different periods of the dairy cows. The successful
      preparation of rat anti-bovine MAdCAM-1 polyclonal antibody and its preliminary
      application in dairy cows provide the foundation for further study of the
      mechanism of anti-inflammation of MAdCAM-1 in dairy cows with subclinical
      mastitis. 

PMID- 26301931
TI  - Preparation and Characterization of a Monoclonal Antibody Against Morphine.
AB  - A monoclonal antibody (MAb) was produced by immunization of a BALB/c mouse with a
      conjugated morphine C6-hemisuccinated derivative (MHS) to cationized bovine serum
      albumin (cBSA). The hybridoma clones were screened by indirect ELISA using MHS
      BSA. The best hybridoma clone was subcloned thrice by limiting dilution. This
      hybridoma was found to be of IgG2b class and subclass and contained lambda light
      chain. The affinity of the MAb to morphine was obtained 2.8*10(9) M(-1). The
      titer of the cell culture supernatant was at least 1:800. The MAb was cross
      reacted with codeine (100%) and apomorphine (16.5%), but not with heroin,
      naloxone, naltrexone, or papaverine. Morphine was conjugated to HRP using a mixed
      anhydride method and a direct competitive ELISA was designed using anti-morphine
      MAb. The assay was sensitive over the 50 ng/mL to 5 MUg/mL concentration range.
      In conclusion, this MAb is useful for the development of immunoassays to measure
      morphine in urine. 

PMID- 26301932
TI  - Preparation of Monoclonal Antibodies Against Bovine Progesterone.
AB  - Female, 8-week-old BALB/c mice were immunized with the progesterone complete
      antigen (P4-BSA). Two monoclonal antibodies (MAbs) against P4, named 8G6 and
      11A11, were obtained by the lymphocyte hybridoma technique. The titers of the
      cell culture supernatant and ascitic fluid of MAb 8G6 were 1: 16,000 and
      1:512,000, respectively, and the titers of the cell culture supernatant and
      ascitic fluid of MAb 11A11 were 1: 8000 and 1:256,000, respectively. The subtypes
      of the MAbs 8G6 and 11A11 were IgMkappa. In specific analysis, both of the two
      MAbs did not react with estradiol. These data demonstrated that the MAbs 8G6 and
      11A11 have a potential use for developing diagnostic reagents of progesterone. 

PMID- 26301933
TI  - Production of Monoclonal Antibodies in Serum-free Media.
AB  - Four hybridoma cell lines (C4B, 10C2G5, 6C5F4C7, 2D10G11) were adapted to grow in
      serum-free conditions. Cell proliferation, viability, and antibody production in
      Nutridoma SP and Ex-Cell HSF 610 media were evaluated and results compared with
      those obtained using DMEM containing 10% fetal bovine serum (control medium).
      Clone C4B showed the best IgG productivity in control medium, but viability and
      number of cells per milliliter were similar for the three media. For clone
      10C2G5, the highest values of cell viability were obtained with both control
      medium and Nutridoma SP; no significant differences in IgG yields and number of
      cells/mL were observed among the three media. Clone 6C5F4C7 provided no
      significant differences when grown in the two serum-free media and in control
      medium. Clone 2D10G11 showed the best IgG productivity in control medium and in
      Ex-Cell HSF 610, even if Ex-Cell HSF 610 provided the lowest number of cells/mL;
      no significant differences among the three media were obtained for viability.
      Purified antibodies produced from each hybridoma cell line grown in serum-free
      media showed a higher degree of purity than those produced by the same cell lines
      grown in control medium. Purified MAbs were also titrated by ELISA to test MAb
      antigen affinity. 

PMID- 26301940
TI  - Robust links between religious/spiritual struggles, psychological distress, and
      well-being in a national sample of American adults.
AB  - This study is one of the first attempts to examine the relationships between
      religious and spiritual struggles (r/s struggles) measured comprehensively and
      indicators of psychological distress (i.e., depressive symptoms, generalized
      anxiety) and well-being (i.e., satisfaction with life, happiness) using a
      nationally representative sample of American adults (N = 2,208) dealing with a
      wide range of major life stressors. In addition, it examines the key question of
      whether these relationships persist after controlling for potentially confounding
      psychosocial/religious influences. Correlational analyses revealed that all 5
      types of the r/s struggles assessed (i.e., divine, demonic, interpersonal, moral,
      ultimate-meaning) correlated significantly positively with both depressive
      symptoms and generalized anxiety, and significantly negatively with both
      satisfaction with life and happiness. Hierarchical regression analyses indicated
      that even after controlling for the effects of demographics and other potentially
      confounding variables (i.e., neuroticism, social isolation, religious commitment)
      the r/s struggle subscales added unique variance to the prediction of all 4
      criterion measures. Theoretical and practical implications of the findings are
      offered, and the limitations of the study are discussed. (PsycINFO Database
      Record 

PMID- 26301941
TI  - Lentivirus-mediated RNA interference of myostatin gene affects MyoD and Myf5 gene
      expression in duck embryonic myoblasts.
AB  - The aim of this study was to construct lentivirus-mediated short hairpin RNA
      (shRNA) vectors targeting the duck MSTN gene and investigate whether these
      vectors can affect the development of duck primary cultured embryonic myoblasts.
      MSTN mRNA levels in the myoblasts were detected using quantitative real-time
      polymerase chain reaction (PCR), cell proliferation was assessed by MTT assays
      and cell differentiation was assayed by photography. MSTN mRNA levels in PLL3.7
      MSTN-shRNA1, PLL3.7-MSTN-shRNA2 and PLL3.7-MSTN-shRNA3 lentivirus-mediated shRNA
      groups were reduced by 61.6%, 76.9% and 79.1%, respectively, compared to control
      cells. Down-regulation of MSTN in duck embryonic myoblasts stimulated cell
      proliferation and inhibited differentiation, accompanied by a greater than
      twofold down-regulation of MyoD expression and up-regulation of Myf5 expression.
      These results revealed that silencing of MSTN changes the development of duck
      embryonic myoblasts by regulating the expression level of MyoD and Myf5 genes. 

PMID- 26301942
TI  - Magnetorheological Elastomer Films with Tunable Wetting and Adhesion Properties.
AB  - We fabricated magnetorheological elastomer (MRE) films consisting of
      polydimethylsiloxane and various concentrations of fluorinated carbonyl iron
      particles. The application of a magnetic field to the MRE film induced changes in
      the surface morphology due to the alignment of the iron particles along the
      magnetic field lines. At low concentrations of iron particles and low magnetic
      field intensities, needle-like microstructures predominated. These structures
      formed more mountain-like microstructures as the concentration of iron particles
      or the magnetic field intensity increased. The surface roughness increased the
      water contact angle from 100 degrees  to 160 degrees  and decreased the sliding
      angle from 180 degrees  to 10 degrees . The wettability and adhesion properties
      changed substantially within a few seconds simply upon application of a magnetic
      field. Cyclical measurements revealed that the transition was completely
      reversible. 

PMID- 26301943
TI  - Facial Plethora: Modern Technology for Quantifying an Ancient Clinical Sign and
      Its Use in Cushing Syndrome.
AB  - CONTEXT: Facial plethora is a clinical sign described since ancient times for a
      variety of diseases. In the 19th century, it was linked to increased blood volume
      or flow, but this has never been proven. Facial plethora is also one of the
      earliest described clinical features of Cushing's syndrome (CS). OBJECTIVE: This
      study aimed to quantify facial plethora changes in CS as an early assessment of
      cure after surgery using noninvasive near-infrared multispectral imaging (MSI).
      DESIGN: The longitudinal cohort study was initiated in August 2012 and completed
      in August 2014. SETTING: Clinical research hospital, National Institutes of
      Health. PATIENTS: Thirty-four of the 38 patients who received surgical treatment
      for CS under protocol 97CH0076 during this period were included. INTERVENTION(S):
      MSI was performed on the right cheek of patients before surgery and 4.9 +/- 3.1
      days afterward. MAIN OUTCOME MEASURE(S): Average blood volume fraction as
      measured by MSI and serum cortisol. RESULTS: All but four of the 28 patients
      (86%) who were assessed as cured by postoperative plasma cortisol measurements of
      < 3 MUg/dL showed a decrease in blood volume fraction (17.7 +/- 0.03 vs 15.8 +/-
      0.03%; P = .0019), whereas an increase was seen in patients with persistent CS
      (18.5 +/- 0.03 vs 21.4 +/- 0.04%; P = .0017). Change in blood volume fraction
      before and after surgery was correlated with postoperative cortisol (rs = 0.58; P
      = .0003). CONCLUSIONS: Clinical data obtained from 34 patients indicate that a
      decrease in facial plethora after surgery, as evidenced by a decrease in blood
      volume fraction, is correlated with CS outcome. This novel technology for the
      first time identified a physiological mechanism associated with an ancient
      clinical sign. Furthermore, as a proof of principle, MSI is a promising early
      marker of cure in patients with CS that complements biochemical and clinical
      data.

PMID- 26301944
TI  - Increased Sensitivity of the Circadian System to Light in Early/Mid-Puberty.
AB  - CONTEXT: Late adolescence is marked by a delay in sleep timing, which is partly
      driven by a delay shift of the circadian timing system. This study examined
      whether the sensitivity of the circadian system to light-the primary entraining
      stimulus to the circadian system-differs between pre- to mid-pubertal and late to
      postpubertal adolescents. OBJECTIVE: The study was designed to determine the
      influence of puberty on the sensitivity of the circadian system to light in
      humans. METHODS: Melatonin suppression to low and moderate light levels was
      assessed in 38 pre- to mid-pubertal (9.1-14.7 years) and 29 late to postpubertal
      (11.5-15.9 years) adolescents. They received 1 hour of four light levels on
      consecutive nights: approximately 0.1 (near-dark baseline condition), 15, 150,
      and 500 lux. One group received evening light beginning at 11:00 pm (n = 39); a
      second group received morning light beginning at 3:00 am (n = 28). Salivary
      melatonin was sampled every 30 minutes. Melatonin suppression for 15, 150, and
      500 lux was calculated relative to unsuppressed baseline levels in the 0.1 lux
      setting, within individuals. RESULTS: The pre- to mid-pubertal group showed
      significantly greater melatonin suppression to 15 lux (9.2 +/- 20.5%), 150 lux
      (26.0 +/- 17.7%), and 500 lux (36.9 +/- 11.4%) during evening light exposure
      compared to the late to postpubertal group (-5.3 +/- 17.7%, 12.5 +/- 17.3%, and
      23.9 +/- 21.7%, respectively; P < .05). No significant differences were seen
      between developmental groups in morning melatonin suppression. CONCLUSION: These
      results indicate support for a greater sensitivity to evening light in early
      pubertal children. The increased sensitivity to light in younger adolescents
      suggests that exposure to evening light could be particularly disruptive to sleep
      regulation for this group.

PMID- 26301945
TI  - Electrocardiographic abnormalities and dyslipidaemic syndrome in children with
      sickle cell anaemia.
AB  - BACKGROUND: Lipid and electrocardiographic (ECG) abnormalities have been reported
      in adults with sickle cell anaemia (SCA) and may reflect underlying structural
      and/or functional damage. However, the relationship between ECG and lipid
      abnormalities among children with sickle cell disease is not fully understood.
      OBJECTIVES: To compare the steady-state lipid and ECG abnormalities in children
      with SCA to the controls and examine the hypothesis that lipid abnormalities are
      closely related to electrocardiographic abnormalities, and therefore are a
      reflection of cardiac damage among these children. METHODS: Clinical, laboratory
      and ECG profiles of 62 children with SCA and 40 age- and gender-matched
      haemoglobin AA controls were compared. The influence of clinical characteristics,
      lipids profiles, markers of haemolysis, and renal and hepatic dysfunction on ECG
      pattern in children with SCA was then determined. RESULTS: The patients had lower
      average diastolic and mean arterial blood pressure, total cholesterol and low
      density lipoprotein cholesterol (LDL-C) levels than the controls, (p = 0.001,
      0.002, 0.000 and 0.000, respectively). The mean triglyceride level was
      significantly higher (p < 0.001), while high-density lipoprotein cholesterol (HDL
      C) levels were comparable (p = 0.858). The cases were about six times more likely
      to have left ventricular hypertrophy than the controls (OR = 6.4, 95% CI = 2.7
      15.6, p = 0.000). Haematocrit level had a negative correlation with QTC (r = 
      0.3, p = 0.016) and QT intervals (r = - 0.3, p = 0.044). Triglyceride levels had
      a positive correlation with the PR interval (r = 0.3, p = 0.012), while serum
      alanine transferase (ALT) concentrations had an inverse correlation with PR
      interval (r = -0.3, p = 0.015). There was no statistical difference in the
      sociodemographic and clinical characteristics of the SCA children with or without
      ECG abnormalities. However, the mean triglyceride and serum ALT levels in those
      with ECG abnormalities were significantly higher than those without (p = 0.007
      and 0.045, respectively). CONCLUSION: Lipid and ECG abnormalities are common in
      children with SCA. Elevated triglyceride and serum ALT levels are possible
      biochemical markers of ECG abnormalities in these patients.

PMID- 26301946
TI  - Simultaneous quantitative determination, identification and qualitative screening
      of pesticides in fruits and vegetables using LC-Q-OrbitrapTM-MS.
AB  - A method based on QuEChERS extraction and LC-quadrupole-OrbitrapTM MS detection
      was established utilising an improved fully non-targeted way of data acquisition
      with and without fragmentation. A full-scan acquisition event without
      fragmentation (resolving power 70,000) was followed by five consecutive
      fragmentation events (variable data independent acquisition - vDIA; resolving
      power 35,000) where all ions from the full-scan range are fragmented. Compared
      with fragmentation in a single event (all-ion fragmentation - AIF), this improves
      both selectivity and sensitivity for the fragment ions, which is beneficial for
      screening performance and identification capability. The method was validated,
      using the data from the same measurements, for two types of analysis:
      quantitation/identification and qualitative screening. The quantitative
      validation, performed according to the guidelines in SANCO/12571/2013, tested the
      performance of the method for 184 compounds in lettuce and orange at two spiking
      levels: 10 and 50 ng g(-1). The validation showed that the vast majority of the
      compounds met the criteria for trueness and precision set in the SANCO guidance
      document. In the qualitative validation the same 184 compounds were used to test
      the untargeted screening capabilities of the method. In this validation the
      compounds were spiked at three levels into 11 different fruit and vegetable
      matrices, which were measured twice on separate days. Taking all data from the
      qualitative validation together, an overall detection rate of 92% was achieved at
      the 10 ng g(-1) level, increasing to 98% at 200 ng g(-1). A screening detection
      limit (as defined in the SANCO guidelines) of 10 ng g(-1) could be achieved for
      134 compounds. For 39 and two pesticides the SDL was 50 and 200 ng g(-1),
      respectively. For the other nine compounds no SDL could be established. The
      identification (ion ratio) criteria as recommended in the SANCO document could be
      met for 93% of the detected pesticide/matrix/concentration combinations. The
      outcome of both validations shows that the described method can be used to
      combine quantitative analysis and the identification of frequently detected
      pesticides (so far typically done using triple quadrupole MS/MS) with a
      qualitative screening to be used for a wide range of less frequent detected
      compounds in one measurement.

PMID- 26301947
TI  - Focal PPK secondary to a novel KRT6C mutation (Pachyonychia congenita-K6c).

PMID- 26301948
TI  - Stabilization of Tetravalent 4f (Ce), 5d (Hf), or 5f (Th, U) Clusters by the
      [alpha-SiW9O34](10-) Polyoxometalate.
AB  - The reaction of Na10[alpha-SiW9O34] with tetravalent metallic cations such as 4f
      ((NH4)2Ce(NO3)6), 5d (HfCl4), or 5f (UCl4 and Th(NO3)4) in a pH 4.7 sodium
      acetate buffer solution leads to the formation of four sandwich-type
      polyoxometalates [Ce4(MU(3)-O)2(SiW9O34)2(CH3COO)2](10-) (1), [U4(MU(3)
      O)2(SiW9O34)2(CH3COO)2](10-) (2), [Th3(MU(3)-O)(MU(2)-OH)3(SiW9O34)2](13-) (3),
      and [Hf3(MU(2)-OH)3(SiW9O34)2](11-) (4). All four compounds consist of a
      polynuclear cluster fragment stabilized by two [alpha-SiW9O34](10-) polyanions.
      Compounds 1 and 2 are isostructural with a tetranuclear core (Ce4, U4), while
      compound 3 presents a trinuclear Th3 core bearing a MU(3)-O-centered bridge. It
      is an unprecedented configuration in the case of the thorium(IV) cluster.
      Compound 4 also possesses a trinuclear Hf3 core but with the absence of the MU(3)
      O bridge. The molecules have been characterized by single-crystal X-ray
      diffraction, (183)W and (29)Si nuclear magnetic resonance (NMR) spectroscopy,
      infrared (IR) spectroscopy, thermogravimetric analysis (TGA), and scanning
      electron microscopy/energy-dispersive X-ray (SEM/EDX) analysis. 

PMID- 26301949
TI  - Production of Nitrous Oxide from Nitrite in Stable Type II Methanotrophic
      Enrichments.
AB  - The coupled aerobic-anoxic nitrous decomposition operation is a new process for
      wastewater treatment that removes nitrogen from wastewater and recovers energy
      from the nitrogen in three steps: (1) NH4(+) oxidation to NO2(-), (2) NO2(-)
      reduction to N2O, and (3) N2O conversion to N2 with energy production. Here, we
      demonstrate that type II methanotrophic enrichments can mediate step two by
      coupling oxidation of poly(3-hydroxybutyrate) (P3HB) to NO2(-) reduction.
      Enrichments grown with NH4(+) and NO2(-) were subject to alternating 48-h aerobic
      and anoxic periods, in which CH4 and NO2(-) were added together in a "coupled"
      mode of operation or separately in a "decoupled mode". Community structure was
      stable in both modes and dominated by Methylocystis. In the coupled mode,
      production of P3HB and N2O was low. In the decoupled mode, significant P3HB was
      produced, and oxidation of P3HB drove reduction of NO2(-) to N2O with ~ 70%
      conversion for >30 cycles (120 d). In batch tests of wasted cells from the
      decoupled mode, N2O production rates increased at low O2 or high NO2(-) levels.
      The results are significant for the development of engineered processes that
      remove nitrogen from wastewater and for understanding of conditions that favor
      environmental production of N2O.

PMID- 26301950
TI  - Simultaneous quantitative mapping of conductivity and susceptibility using a
      double-echo ultrashort echo time sequence: Example using a hematoma evolution
      study.
AB  - PURPOSE: The primary purpose of this study is to propose a method for the
      simultaneous quantitative three-dimensional (3D) mapping of conductivity and
      susceptibility using double-echo ultrashort echo time (UTE) imaging. The
      secondary purpose is to investigate the changes of these properties over time
      during in vitro hematoma evolution in blood samples. METHODS: The first and
      second set of echo data for a UTE sequence were used to perform quantitative
      conductivity mapping (QCM) and quantitative susceptibility mapping (QSM),
      respectively. A simulation study was conducted to determine the echo time (TE)
      range that was acceptable for QCM. Subsequently, a NaCl phantom experiment and in
      vivo 3D QCM and QSM demonstrations were performed. The changes in electromagnetic
      (EM) properties over time were studied using in vitro blood coagulation
      experiments with venous blood from healthy volunteers. RESULTS: Quantitative and
      qualitative analyses showed small differences in the QCM for TE values up to 300
      MUs. The estimated conductivity and susceptibility values monotonically increased
      during the first few hours of the hematoma evolution experiments. However,
      although the susceptibility values continued to increase, the conductivity values
      were steady after 24 h. CONCLUSION: The proposed method can be useful for
      determining EM property changes (including those during hemorrhage) and providing
      additional information about the state of the blood. Magn Reson Med 76:214-221,
      2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 26301951
TI  - Modelling impacts of performance on the probability of reproducing, and thereby
      on productive lifespan, allow prediction of lifetime efficiency in dairy cows.
AB  - Reproductive success is a key component of lifetime efficiency - which is the
      ratio of energy in milk (MJ) to energy intake (MJ) over the lifespan, of cows. At
      the animal level, breeding and feeding management can substantially impact milk
      yield, body condition and energy balance of cows, which are known as major
      contributors to reproductive failure in dairy cattle. This study extended an
      existing lifetime performance model to incorporate the impacts that performance
      changes due to changing breeding and feeding strategies have on the probability
      of reproducing and thereby on the productive lifespan, and thus allow the
      prediction of a cow's lifetime efficiency. The model is dynamic and stochastic,
      with an individual cow being the unit modelled and one day being the unit of
      time. To evaluate the model, data from a French study including Holstein and
      Normande cows fed high-concentrate diets and data from a Scottish study including
      Holstein cows selected for high and average genetic merit for fat plus protein
      that were fed high- v. low-concentrate diets were used. Generally, the model
      consistently simulated productive and reproductive performance of various
      genotypes of cows across feeding systems. In the French data, the model
      adequately simulated the reproductive performance of Holsteins but significantly
      under-predicted that of Normande cows. In the Scottish data, conception to first
      service was comparably simulated, whereas interval traits were slightly under
      predicted. Selection for greater milk production impaired the reproductive
      performance and lifespan but not lifetime efficiency. The definition of lifetime
      efficiency used in this model did not include associated costs or herd-level
      effects. Further works should include such economic indicators to allow more
      accurate simulation of lifetime profitability in different production scenarios. 

PMID- 26301952
TI  - Estrogen receptor-beta in mitochondria: implications for mitochondrial
      bioenergetics and tumorigenesis.
AB  - Estrogen enhances mitochondrial function by enhancing mitochondrial biogenesis
      and sustaining mitochondrial energy-transducing capacity. Shifts in mitochondrial
      bioenergetic pathways from oxidative phosphorylation to glycolysis have been
      hypothesized to be involved in estrogen-induced tumorigenesis. Studies have shown
      that mitochondria are an important target of estrogen. Estrogen receptor-beta
      (ERbeta) has been shown to localize to mitochondria in a ligand-dependent or 
      independent manner and can affect mitochondrial bioenergetics and anti-apoptotic
      signaling. However, the functional role of mitochondrial ERbeta in tumorigenesis
      remains unclear. Clinical studies of ERbeta-related tumorigenesis have shown that
      ERbeta stimulates mitochondrial metabolism to meet the high energy demands of
      processes such as cell proliferation, cell survival, and transformation. Thus, in
      elucidating the precise role of mitochondrial ERbeta in cell transformation and
      tumorigenesis, it will be particularly valuable to explore new approaches for the
      development of medical treatments targeting mitochondrial ERbeta-mediated
      mitochondrial function and preventing apoptosis. 

PMID- 26301953
TI  - Insight into the transcriptome of Arthrobotrys conoides using high throughput
      sequencing.
AB  - Arthrobotrys conoides is a nematode-trapping fungus belonging to Orbiliales,
      Ascomycota group, and traps prey nematodes by means of adhesive network. Fungus
      has a potential to be used as a biocontrol agent against plant parasitic
      nematodes. In the present study, we characterized the transcriptome of A.
      conoides using high-throughput sequencing technology and characterized its
      virulence unigenes. Total 7,255 cDNA contigs with an average length of 425 bp
      were generated and 6184 (61.81%) transcripts were functionally annotated and
      characterized. Majority of unigenes were found analogous to the genes of plant
      pathogenic fungi. A total of 1749 transcripts were found to be orthologous with
      eukaryotic proteins of KOG database. Several carbohydrate active enzymes and
      peptidases were identified. We also analyzed classically and nonclassically
      secreted proteins and confirmed by BLASTP against fungal secretome database. A
      total of 916 contigs were analogous to 556 unique proteins of Pathogen Host
      Interaction (PHI) database. Further, we identified 91 unigenes homologous to the
      database of fungal virulence factor (DFVF). A total of 104 putative protein
      kinases coding transcripts were identified by BLASTP against KinBase database,
      which are major players in signaling pathways. This study provides a
      comprehensive look at the transcriptome of A. conoides and the identified
      unigenes might have a role in catching and killing prey nematodes by A. conoides.

PMID- 26301954
TI  - Women's Preference for a Male Acquaintance Enhances Social Reward Processing of
      Material Goods in the Anterior Cingulate Cortex.
AB  - Men, like the male of many animal species, use gifts to build satisfactory
      relationships with a desired woman. From the woman's perspective, all gifts are
      not always equally rewarding; the reward value of a gift depends on two factors:
      (1) the giver and (2) the type of the gift (the gift's social meaning). In this
      study, we investigated how these two factors interactively determine the reward
      value of a gift. Specifically, we examined how the neural processing for
      understanding a gift's social meaning is modulated by preferences for the giver.
      We performed a functional magnetic resonance imaging (fMRI) study in which a
      female participant was asked to judge a gift from a male she was acquainted with
      in real life. We examined the interactive effects between (1) the female
      participant's attitude toward the male acquaintance (liked vs. uninteresting) and
      (2) the type of the gift (romantic [e.g., bouquet, earrings, and perfumes] vs.
      non-romantic [e.g., pencils, memo pad, and moneybox]). We found that preference
      for an acquaintance selectively modulated activity in the anterior cingulate
      cortex (ACC) in response to romantic gifts, compared to non-romantic gifts. In
      contrast, if the woman was indifferent toward an acquaintance, no activity
      modulation was observed in this area for the same gifts. In addition, the ACC
      showed functional connectivity with the supplementary motor area/dorsal ACC
      (SMA/dACC), an area within the dorsal mediofrontal cortex, suggesting that it
      integrates action monitoring and emotional and cognitive processing in decision
      making. These results suggest that attitude toward an opposite sex member has a
      modulatory role in recognizing the social meaning of material goods--preference
      for the member is a powerful modulator of social reward processing.

PMID- 26301955
TI  - Mucocutaneous pyoderma gangrenosum due to trisomy 8 neutrophilic infiltrates in a
      patient with myelodysplastic syndrome.

PMID- 26301956
TI  - Klf15 Is Critical for the Development and Differentiation of Drosophila
      Nephrocytes.
AB  - Insect nephrocytes are highly endocytic scavenger cells that represent the only
      invertebrate model for the study of human kidney podocytes. Despite their
      importance, nephrocyte development is largely uncharacterised. This work tested
      whether the insect ortholog of mammalian Kidney Kruppel-Like Factor (Klf15), a
      transcription factor required for mammalian podocyte differentiation, was
      required for insect nephrocyte development. It was found that expression of
      Drosophila Klf15 (dKlf15, previously known as Bteb2) was restricted to the only
      two nephrocyte populations in Drosophila, the garland cells and pericardial
      nephrocytes. Loss of dKlf15 function led to attrition of both nephrocyte
      populations and sensitised larvae to the xenotoxin silver nitrate. Although
      pericardial nephrocytes in dKlf15 loss of function mutants were specified during
      embryogenesis, they failed to express the slit diaphragm gene sticks and stones
      and did not form slit diaphragms. Conditional silencing of dKlf15 in adults led
      to reduced surface expression of the endocytic receptor Amnionless and loss of in
      vivo scavenger function. Over-expression of dKlf15 increased nephrocyte numbers
      and rescued age-dependent decline in nephrocyte function. The data place dKlf15
      upstream of sns and Amnionless in a nephrocyte-restricted differentiation pathway
      and suggest dKlf15 expression is both necessary and sufficient to sustain
      nephrocyte differentiation. These findings explain the physiological relevance of
      dKlf15 in Drosophila and imply that the role of KLF15 in human podocytes is
      evolutionarily conserved. 

PMID- 26301957
TI  - Versatile grasping ability in power-grip actions by tufted capuchin monkeys
      (Sapajus spp.).
AB  - OBJECTIVES: Capuchin monkeys are well known to have a high degree of manual
      dexterity. In this study, we assessed the variability of capuchin grasping
      actions involving power grips, i.e., manual actions in which the object is
      grasped between the palm and one or several parts of the fingers and that do not
      necessarily involve individually controlled finger movements. Planning abilities
      in executing actions were also evaluated. METHODS: Twenty tufted capuchins
      (Sapajus spp.) were tested in a task requiring individuals to grasp a dowel
      inserted into a vertical tube. We examined their grasping techniques, focusing on
      the following aspects: (i) the different hand postures made during grasping, (ii)
      the frequency of thumb use in opposition to the other fingers, (iii) the
      asymmetric use of the hands, and (iv) the configuration of the grasping action
      for the purpose of comfortably bringing the food to the mouth. RESULTS: Eight
      power-grip variants were identified, with individual capuchins performing an
      average of more than five different grips. The use of the thumb in opposition to
      the other areas of the hand, as reported in studies of precision grips, also
      appears to be a common feature in power grips. No evidence of group-level manual
      asymmetries was found. Adult capuchins were better than immature individuals in
      planning grasping actions in relation to following task demands. DISCUSSION:
      Overall, these findings clarify the extent to which manual dexterity and
      cognitive abilities can be expressed in the grasping tasks of highly manually
      skilled primate species.

PMID- 26301958
TI  - Flash Expansion Threshold in Whirligig Swarms.
AB  - In the selfish herd hypothesis, prey animals move toward each other to avoid the
      likelihood of being selected by a predator. However, many grouped animals move
      away from each other the moment before a predator attacks. Very little is known
      about this phenomenon, called flash expansion, such as whether it is triggered by
      one individual or a threshold and how information is transferred between group
      members. We performed a controlled experiment with whirligig beetles in which the
      ratio of sighted to unsighted individuals was systematically varied and emergent
      flash expansion was measured. Specifically, we examined: the percentage of
      individuals in a group that startled, the resulting group area, and the longevity
      of the flash expansion. We found that one or two sighted beetles in a group of 24
      was not enough to cause a flash expansion after a predator stimulus, but four
      sighted beetles usually initiated a flash expansion. Also, the more beetles that
      were sighted the larger the resulting group area and the longer duration of the
      flash expansion. We conclude that flash expansion is best described as a
      threshold event whose adaptive value is to prevent energetically costly false
      alarms while quickly mobilizing an emergent predator avoidance response. This is
      one of the first controlled experiments of flash expansion, an important emergent
      property that has applications to understanding collective motion in swarms,
      schools, flocks, and human crowds. Also, our study is a convincing demonstration
      of social contagion, how the actions of one individual can pass through a group. 

PMID- 26301960
TI  - Correction: Heuristics to Evaluate Interactive Systems for Children with Autism
      Spectrum Disorder (ASD).

PMID- 26301959
TI  - Association Between Transient Newborn Hypoglycemia and Fourth-Grade Achievement
      Test Proficiency: A Population-Based Study.
AB  - IMPORTANCE: Prolonged neonatal hypoglycemia is associated with poor long-term
      neurocognitive function. However, little is known about an association between
      early transient newborn hypoglycemia and academic achievement. OBJECTIVE: To
      determine if early (within the first 3 hours of life) transient hypoglycemia (a
      single initial low glucose concentration, followed by a second value above a
      cutoff) is associated with subsequent poor academic performance. DESIGN, SETTING,
      AND PARTICIPANTS: A retrospective population-based cohort study of all infants
      born between January 1, 1998, and December 31, 1998, at the University of
      Arkansas for Medical Sciences who had at least 1 recorded glucose concentration
      (a universal newborn glucose screening policy was in effect) was conducted.
      Medical record data from newborns with normoglycemia or transient hypoglycemia
      were matched with their student achievement test scores in 2008 from the Arkansas
      Department of Education and anonymized. Logistic regression models were developed
      to evaluate the association between transient hypoglycemia and school-age
      achievement test proficiency based on perinatal factors. Common hypoglycemia
      cutoffs of a glucose level less than 35 mg/dL (primary) and less than 40 and 45
      mg/dL (secondary) were investigated. All 1943 normoglycemic and transiently
      hypoglycemic infants (23-42 weeks' gestation) were eligible for inclusion in the
      study. Infants with prolonged hypoglycemia, congenital anomalies, or chromosomal
      abnormalities were excluded from the study. EXPOSURE: Hypoglycemia as a newborn.
      MAIN OUTCOMES AND MEASURES: The primary outcome was proficiency on fourth-grade
      literacy and mathematics achievement tests at age 10 years. We hypothesized a
      priori that newborns with early transient hypoglycemia would be less proficient
      on fourth-grade achievement tests compared with normoglycemic newborns. RESULTS:
      Perinatal data were matched with fourth-grade achievement test scores in 1395
      newborn-student pairs (71.8%). Transient hypoglycemia (glucose level <35, <40,
      and <45 mg/dL) was observed in 6.4% (89 of 1395), 10.3% (143 of 1395), and 19.3%
      (269 of 1395) of newborns, respectively. After controlling for gestational age
      group, race, sex, multifetal gestation, insurance status, maternal educational
      level and socioeconomic status, and gravidity, transient hypoglycemia was
      associated with decreased probability of proficiency on literacy and mathematics
      fourth-grade achievement tests. For the 3 hypoglycemia cutoffs, the adjusted odds
      ratios (95% CIs) for literacy were 0.49 (0.28-0.83), 0.43 (0.28-0.67), and 0.62
      (0.45-0.85), respectively, and the adjusted odds ratios (95% CIs) for mathematics
      were 0.49 (0.29-0.82), 0.51 (0.34-0.78), and 0.78 (0.57-1.08), respectively.
      CONCLUSIONS AND RELEVANCE: Early transient newborn hypoglycemia was associated
      with lower achievement test scores at age 10 years. Given that our findings are
      serious and contrary to expert opinion, the results need to be validated in other
      populations before universal newborn glucose screening should be adopted.

PMID- 26301961
TI  - The Association Between Aqueous Connective Tissue Growth Factor and the Severity
      of Age-related Cataracts as Graded by the Lens Opacities Classification System
      III.
AB  - PURPOSE: To evaluate the relationship between aqueous humor concentrations of
      connective tissue growth factor (CTGF) and the severity of age-related cataracts.
      MATERIALS AND METHODS: We conducted a prospective clinical study on 43 eyes of 43
      patients with senile cataracts scheduled to undergo routine phacoemulsification
      surgery. Before surgery, all patients were graded for cataract severity using the
      Lens Opacities Classification System III in terms of four features: nuclear
      opalescence (NO), nuclear color (NC), cortical cataracts (C), and posterior sub
      capsular cataracts (P). During surgery, aqueous humor samples were obtained from
      all patients, and sandwich enzyme-linked immunosorbent assays (ELISAs) were used
      to determine CTGF concentrations. To assess any relationship between cataract
      severity and CTGF levels of the aqueous humor, various correlation analyses and
      multiple linear regression were used. RESULTS: We found a positive correlation
      between the overall cataract grade and aqueous CTGF level (p < 0.05). In
      addition, four features of the cataract grade (nuclear opalescence, nuclear
      color, cortical cataract and posterior sub-capsular cataract) were positively
      correlated with the aqueous CTGF concentration (p < 0.05). The final regression
      model identified overall cataract grade as an independent predictor of increased
      CTGF levels in the aqueous humor (p < 0.05). CONCLUSIONS: CTGF tends to increase
      in the aqueous humor as the severity of age-related cataracts increases.
      Therefore, this cytokine may play an important role in the pathogenesis of age
      related cataracts. Additional studies are required for clarification of this
      finding.

PMID- 26301963
TI  - Retrieval practice can insulate items against intralist interference: Evidence
      from the list-length effect, output interference, and retrieval-induced
      forgetting.
AB  - This study sought to determine whether nonselective retrieval practice after
      study can reduce memories' susceptibility to intralist interference, as it is
      observed in the list-length effect, output interference, and retrieval-induced
      forgetting. Across 3 experiments, we compared the effects of nonselective
      retrieval practice and restudy on previously studied material with regard to
      these 3 forms of episodic forgetting. When study of an item list was followed by
      a restudy cycle, recall from a longer list was worse than recall from a shorter
      list (list-length effect), preceding recall of studied nontarget items impaired
      recall of the list's target items (output interference), and repeated selective
      retrieval of some list items attenuated recall of other nonretrieved items at
      test (retrieval-induced forgetting). In contrast, none of these effects arose
      when study of the list was followed by a nonselective retrieval cycle. The
      findings are consistent with a combination of contextual variability theory and a
      variant of study-phase retrieval theory that assumes that retrieval can create
      more distinct context features for retrieved items than restudy does for
      restudied items, thus reducing items' susceptibility to interference relative to
      restudy cycles. The findings add to the view that nonselective retrieval practice
      can stabilize and consolidate memories.

PMID- 26301962
TI  - Spoken word recognition and serial recall of words from components in the
      phonological network.
AB  - Network science uses mathematical techniques to study complex systems such as the
      phonological lexicon (Vitevitch, 2008). The phonological network consists of a
      giant component (the largest connected component of the network) and lexical
      islands (smaller groups of words that are connected to each other, but not to the
      giant component). To determine if the component that a word resided in influenced
      lexical processing, language-related tasks (naming, lexical decision, and serial
      recall) were used to compare the processing of words from the giant component and
      from lexical islands. Results showed that words from lexical islands were
      recognized more quickly and recalled more accurately than words from the giant
      component. These findings can be accounted for via the diffusion of activation
      across a network. Implications for models of spoken word recognition and network
      science are also discussed.

PMID- 26301964
TI  - Effect of Ventilation Support on Oxidative Stress and Ischemia-Modified Albumin
      in Neonates.
AB  - BACKGROUND AND OBJECTIVE: Mechanical ventilation (MV) can induce oxidative
      stress, which plays a critical role in pulmonary injury in intubated neonates.
      Ischemia-modified albumin (IMA)-a variant of human serum albumin-is a novel
      biomarker of myocardial ischemia that occurs due to reactive oxygen species
      during ischemic insult. This study aimed to investigate IMA production due to
      oxidative stress induced during MV in neonates. MATERIALS AND METHODS: This study
      included 17 neonates that were ventilated using synchronized intermittent
      mechanical ventilation (SIMV; SIMV group) and 20 neonates ventilated using
      continuous positive airway pressure (CPAP; CPAP group). Blood samples were
      collected from each neonate during ventilation support and following cessation of
      ventilation support. Total antioxidant capacity (TAC) and total oxidant status
      (TOS) were measured using the Erel method. IMA was measured via an enzyme-linked
      immunosorbent assay kit (Cusabio Biotech Co., Ltd., Wuhan, China). The oxidant
      stress index (OSI) was calculated as OSI = TOS/TAC. Statistical analysis was
      performed using SPSS v.18.0 (SPSS Inc., Chicago, IL) for Windows. RESULTS: Among
      the neonates included in the study, mean gestational age was 34.7 +/- 3.8 weeks,
      mean birth weight was 2,553 +/- 904 g, and 54% were premature. There were not any
      significant differences in mean gestational age or birth weight between the SIMV
      and CPAP groups. Among the neonates in both the groups, mean IMA, TOS, and OSI
      levels were significantly higher during ventilation support (102.2 +/- 9.3 IU mL(
      1), 15.5 +/- 1.3 umol H2O2 equivalent L(-1), and 0.85 +/- 0.22 arbitrary units
      [ABU], respectively), as compared with following cessation of ventilation support
      (82.9 +/- 11.9 IU mL(-1), 13.4 +/- 1.3 umol H2O2 equivalent L(-1), and 0.64 +/-
      0.14 ABU, respectively) (p = 0.001). Among all the neonates in the study, mean
      TAC was significantly lower during ventilation support than the postventilation
      support (1.82 +/- 0.28 mmol 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic
      acid [Trolox] equivalent L(-1) vs. 2.16 +/- 0.31 mmol Trolox equivalent L(-1)) (p
      = 0.001). There were no significant differences in mean TAC, OSI, or IMA levels
      between the SIMV and CPAP groups. The mean TOS level during ventilation support
      and the mean difference in TOS between during and postventilation support was
      significantly greater in the CPAP group than in the SIMV group. There were no
      significant relationships between the mean TOS, TAC, OSI, or IMA levels, and
      gestational age of the neonates. CONCLUSION: SIMV and CPAP activated the
      oxidative stress and increased the IMA level in neonates; therefore, measurement
      of IMA and oxidant markers may be useful in the follow-up of lung injury in
      neonates due to ventilation support. Additional prospective studies are needed to
      compare the effects of various ventilation methods on oxidative stress and the
      IMA level in neonates.

PMID- 26301965
TI  - Early-onset acute kidney injury is a poor prognostic sign for allogeneic SCT
      recipients.
AB  - Acute kidney injury (AKI) following stem-cell transplantation (SCT) contributes
      to a poor prognosis, yet its impact may vary depending on the timing of AKI
      onset. A prospective cohort study was performed to understand the significance of
      the onset timing in 103 allogeneic SCT (allo-SCT) recipients. AKI prior to stem
      cell engraftment was defined as early AKI and subsequently occurring AKI as late
      AKI. Propensity score (PS) for early AKI was calculated using a logistic
      regression model to reduce confounding effects related to differences in clinical
      background between the early and late AKI groups. The cumulative incidences of
      early and late AKI were 22.3% and 54.9%, respectively. Non-relapse mortality
      (NRM) was 39.1% and 7.0%, and overall survival (OS) was 56.5% and 90.9% in early
      and late AKI at 100 days after AKI, respectively (P<0.001). The cumulative
      incidence of chronic kidney disease (CKD) over 2 years after SCT was 41.5% and
      19.1% in early and late AKI, respectively (P=0.048). Logistic regression analysis
      adjusted for the PS showed that early AKI was significantly associated with OS
      (odds ratio (95% confidence interval); 4.63 (1.15-21.4), P=0.031) but with
      neither NRM (1.25 (0.28-5.33), P=0.766) nor CKD (1.85 (0.41-8.60), P=0.422). In
      conclusion, early AKI may portend a poor survival for allo-SCT recipients. 

PMID- 26301966
TI  - Incidence and risk factors for ocular GVHD after allogeneic hematopoietic stem
      cell transplantation.
AB  - We analyzed the incidence and risk factors for ocular GVHD in patients undergoing
      allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Korea. In this
      retrospective, noncomparative, observational study, 635 subjects were included
      who had at least 2 years of follow-up ophthalmological examinations after allo
      HSCT from 2009 to 2012 at Seoul St Mary's Hospital, Seoul, Korea. The mean
      duration between allo-HSCT and onset of ocular GVHD was 225.5+/-194.3 days. The
      adjusted incidence for acute ocular GVHD was 1.33% and that for chronic GVHD was
      33.33%. In the multivariate analysis, preexisting diabetes mellitus (odds ratio
      (OR): 4.22, 95% confidence interval (CI): 1.66-10.72), repeated allo-HSCT (OR:
      29.10, 95% CI: 1.02-8.28) and the number of organs that chronically developed
      GVHD by stage I (OR: 14.63, 95% CI: 9.81-21.84) increased risk of ocular GVHD.
      Careful monitoring of ocular GVHD is needed in patients with chronic GVHD in
      multiple organs and preexisting diabetes. 

PMID- 26301968
TI  - Numerical impairment of nestin(+) bone marrow niches in acute GvHD after
      allogeneic hematopoietic stem cell transplantation for AML.
AB  - The nestin(+) perivascular bone marrow (BM) stem cell niche (N(+)SCN) may be
      involved in GvHD. To investigate whether acute GvHD (aGvHD) reduces the number of
      N(+)SCN, we examined patients with AML who had undergone allogeneic hematopoietic
      stem cell transplantation. In the test cohort (n=8), the number of N(+)SCN per
      mm(2) in BM biopsies was significantly reduced in aGvHD patients at the time of
      aGvHD compared with patients who did not have aGvHD (1.2+/-0.78 versus 2.6+/
      0.93, P=0.04). In the validation cohort (n=40), the number of N(+)SCN was reduced
      (1.9+/-0.99 versus 2.6+/-0.90 N(+)SCN/mm(2), P=0.05) in aGvHD patients. Receiver
      operating curves suggested that the cutoff score that best discriminated between
      patients with and without aGvHD was 2.29 N(+)SCN/mm(2). Applying this cutoff
      score, 9/11 patients with clinically relevant aGvHD (?grade 2) and 13/20 with any
      type of GvHD had decreased N(+)SCN numbers compared with only 10/29 patients
      without clinically relevant aGvHD (P=0.007) and 6/20 patients without any type of
      GvHD (P=0.028). In patients tracked over time, N(+)SCN density returned to normal
      after aGvHD resolved or remained stable in patients who did not have aGvHD. Our
      results show a decrease in the number of N(+)SCN in aGvHD. 

PMID- 26301970
TI  - Serum anti-BPAG1 autoantibody level is not a useful biomarker for cutaneous
      melanoma.

PMID- 26301969
TI  - Sirolimus, tacrolimus and antithymocyte globulin as GVHD prophylaxis in HLA
      mismatched unrelated donor hematopoietic cell transplantation: a single
      institution experience.

PMID- 26301967
TI  - Contribution of chemotherapy mobilization to disease control in multiple myeloma
      treated with autologous hematopoietic cell transplantation.
AB  - In patients with multiple myeloma (MM) undergoing autologous hematopoietic cell
      transplantation (auto-HCT), peripheral blood progenitor cells may be collected
      following mobilization with growth factor alone (GF) or cytotoxic chemotherapy
      plus GF (CC+GF). It is uncertain whether the method of mobilization affects post
      transplant outcomes. We compared these mobilization strategies in a retrospective
      analysis of 968 patients with MM from the Center for International Blood and
      Marrow Transplant Research database who received an auto-HCT in the US and Canada
      between 2007 and 2012. The kinetics of neutrophil engraftment (?0.5 * 10(9)/L)
      was similar between groups (13 vs 13 days, P=0.69) while platelet engraftment
      (?20 * 10(9)/L) was slightly faster with CC+GF (19 vs 18 days, P=0.006). Adjusted
      3-year PFS was 43% (95% confidence interval (CI) 38-48) in GF and 40% (95% CI 35
      45) in CC+GF, P=0.33. Adjusted 3-year OS was 82% (95% CI 78-86) vs 80% (95% CI 75
      84), P=0.43 and adjusted 5-year OS was 62% (95% CI 54-68) vs 60% (95% CI 52-67),
      P=0.76, for GF and CC+GF, respectively. We conclude that MM patients undergoing
      auto-HCT have similar outcomes irrespective of the method of mobilization and
      found no evidence that the addition of chemotherapy to mobilization contributes
      to disease control. 

PMID- 26301971
TI  - Conjugated Cofactor Enables Efficient Temperature-Independent Electronic
      Transport Across ~6 nm Long Halorhodopsin.
AB  - We observe temperature-independent electron transport, characteristic of
      tunneling across a ~6 nm thick Halorhodopsin (phR) monolayer. phR contains both
      retinal and a carotenoid, bacterioruberin, as cofactors, in a trimeric protein
      chromophore complex. This finding is unusual because for conjugated oligo-imine
      molecular wires a transition from temperature-independent to -dependent electron
      transport, ETp, was reported at ~4 nm wire length. In the ~6 nm long phR, the ~4
      nm 50-carbon conjugated bacterioruberin is bound parallel to the alpha-helices of
      the peptide backbone. This places bacterioruberin's ends proximal to the two
      electrodes that contact the protein; thus, coupling to these electrodes may
      facilitate the activation-less current across the contacts. Oxidation of
      bacterioruberin eliminates its conjugation, causing the ETp to become temperature
      dependent (>180 K). Remarkably, even elimination of the retinal-protein covalent
      bond, with the fully conjugated bacterioruberin still present, leads to
      temperature-dependent ETp (>180 K). These results suggest that ETp via phR is
      cooperatively affected by both retinal and bacterioruberin cofactors. 

PMID- 26301972
TI  - Therapeutic potential of curcumin and curcumin analogues in rheumatology.

PMID- 26301973
TI  - Chronic and episodic interpersonal stress as statistically unique predictors of
      depression in two samples of emerging adults.
AB  - Few studies comprehensively evaluate which types of life stress are most strongly
      associated with depressive episode onsets, over and above other forms of stress,
      and comparisons between acute and chronic stress are particularly lacking. Past
      research implicates major (moderate to severe) stressful life events (SLEs), and
      to a lesser extent, interpersonal forms of stress; research conflicts on whether
      dependent or independent SLEs are more potent, but theory favors dependent SLEs.
      The present study used 5 years of annual diagnostic and life stress interviews of
      chronic stress and SLEs from 2 separate samples (Sample 1 N = 432; Sample 2 N =
      146) transitioning into emerging adulthood; 1 sample also collected early
      adversity interviews. Multivariate analyses simultaneously examined multiple
      forms of life stress to test hypotheses that all major SLEs, then particularly
      interpersonal forms of stress, and then dependent SLEs would contribute unique
      variance to major depressive episode (MDE) onsets. Person-month survival analysis
      consistently implicated chronic interpersonal stress and major interpersonal SLEs
      as statistically unique predictors of risk for MDE onset. In addition, follow-up
      analyses demonstrated temporal precedence for chronic stress; tested differences
      by gender; showed that recent chronic stress mediates the relationship between
      adolescent adversity and later MDE onsets; and revealed interactions of several
      forms of stress with socioeconomic status (SES). Specifically, as SES declined,
      there was an increasing role for noninterpersonal chronic stress and
      noninterpersonal major SLEs, coupled with a decreasing role for interpersonal
      chronic stress. Implications for future etiological research were discussed.

PMID- 26301975
TI  - Frailty: Scaling from Cellular Deficit Accumulation?
AB  - Cells age in association with deficit accumulation via mechanisms that are far
      from fully defined. Even so, how deficits might scale up from the subcellular
      level to give rise to clinically evident age-related changes can be investigated.
      This 'scaling problem' can be viewed either as a series of little-related events
      that reflect discrete processes--such as the development of particular diseases-
      or as a stochastic process with orderly progression at the systems level,
      regardless of which diseases are present. Some recent evidence favors the latter
      hypothesis, but determining the best approach to study how deficits scale remains
      a key goal for understanding aging. In consequence, approaching the problem of
      frailty as one of the scaling of subcellular deficits has implications for
      understanding aging. Considering the cumulative effects of many small deficits
      appears to allow for the observation of important aspects of the behavior of
      systems that are close to failure. Mathematical modeling offers useful
      possibilities in clarifying the extent to which different clinical scales measure
      different phenomena. Even so, to be useful, mathematical modelling must be
      clinically coherent in addition to mathematically sound. In this regard, queuing
      appears to offer some potential for investigating how deficits originate and
      accumulate.

PMID- 26301976
TI  - Assessment of Frailty in Animal Models.
AB  - Animal models have contributed greatly to our understanding of the biology of
      aging and have been used to test new potential interventions to enhance survival.
      However, whether these interventions can modify frailty in animals is not yet
      clear, in part because until recently, frailty had not been considered in animal
      studies of aging. This review is focused on investigations that have attempted to
      address the issue of frailty, or aspects of frailty, in animal models, including
      invertebrate and vertebrate models. Some studies have used skeletal muscle
      weakness or sarcopenia as a surrogate for frailty in aging animals. Others have
      used genetically altered mice, in which components of human frailty such as
      inflammation are enhanced. This review also explores a novel approach to quantify
      frailty with a 'frailty index' based on deficit accumulation in aging animals.
      The concept of the frailty index is well established in the clinical literature,
      but recent work suggests that this approach can also be used to measure frailty
      in aging animals. The ability to quantify frailty in animals is a major step
      forward in the effort to understand the biology of frailty and to develop new
      clinical interventions.

PMID- 26301974
TI  - Functional coherence of insula networks is associated with externalizing
      behavior.
AB  - The externalizing spectrum encompasses a range of maladaptive behaviors,
      including substance-use problems, impulsivity, and aggression. Although previous
      literature has linked externalizing behaviors with prefrontal and amygdala
      abnormalities, recent studies suggest insula functionality is implicated. This
      study investigated the relation between insula functional coherence and
      externalizing in a large community sample (N = 244). Participants underwent a
      resting functional MRI scan. Three nonartifactual intrinsic connectivity networks
      (ICNs) substantially involving the insula were identified after completing
      independent components analysis. Three externalizing domains-general
      disinhibition, substance abuse, and callous aggression-were measured with the
      Externalizing Spectrum Inventory. Regression models tested whether within-network
      coherence for the 3 insula ICNs was related to each externalizing domain.
      Posterior insula coherence was positively associated with general disinhibition
      and substance abuse. Anterior insula/ventral striatum/anterior cingulate network
      coherence was negatively associated with general disinhibition. Insula coherence
      did not relate to the callous aggression domain. Follow-up analyses indicated
      specificity for insula ICNs in their relation to general disinhibition and
      substance abuse as compared with other frontal and limbic ICNs. This study found
      insula network coherence was significantly associated with externalizing
      behaviors in community participants. Frontal and limbic ICNs containing less
      insular cortex were not related to externalizing. Thus, the neural synchrony of
      insula networks may be central for understanding externalizing psychopathology.

PMID- 26301977
TI  - Frailty, Inflammation and Immunosenescence.
AB  - Frailty is a still-evolving concept of a complex phenomenon. There are several
      algorithms and strategies for assessing frailty syndrome, but currently, no
      universally accepted definition or measurement protocol has been determined.
      Consequently, the biological cause(s) of frailty are also poorly defined. Much
      circumstantial experimental data point to the dysregulation of several key
      physiological systems, including the neuroendocrine, musculoskeletal, metabolic
      and immune/inflammatory systems, resulting from alterations in functional
      reserves. Immune dysregulation and inflammation as causes of frailty have gained
      some support from the results of longitudinal studies, but a true causal
      relationship has not been established. This chapter will describe the
      immune/inflammatory alterations found in frailty and their putative causal
      relationships with this state.

PMID- 26301978
TI  - Sex Differences in Frailty.
AB  - Although women live longer lives than men, they tend to have poorer health
      status. Here, we review the biological and socio-behavioral factors that may
      contribute to this sex-frailty paradox. The conceptual framework that frailty is
      a product of the environment and the recovery rate provides a new understanding
      of women's frailty burden. Even developed countries may present an environment
      more adverse for women, and lifestyle factors may increase women's vulnerability
      to stochastic subcellular events that increase recovery time. The frailty index
      does not reach the theoretical maximal value of 1; its limit is lower in men
      (0.61) compared to women (0.69). Perhaps deterministic characteristics omitted in
      current deficit counts, such as reduced emotional adaptability, are more
      prevalent in men. Alternatively, different limits may result from quantitative
      evolutionary design, such as a fitness-frailty pleiotropy in men or fertility
      frailty pleiotropy in women. The engineering principle of safety factors (maximal
      capacity divided by routine functioning) may also be informative. If the human
      system has the same safety factor as its organs (approximately 2.5), men may be
      'calibrated' around a frailty index of 0.244, compared to 0.276 for women.
      Because 0.25 represents the tipping point between functional independence and
      reliance on others, evolutionary design may have allowed for some limited
      dependence in women, perhaps motivated by the perinatal period.

PMID- 26301979
TI  - Frailty and the Microbiome.
AB  - From the moment of birth, the human body plays host to a rich diversity of
      microbes. Body sites such as the skin, the gut and the mouth support communities
      of microorganisms (collectively known as the microbiome) that are both numerous
      and diverse. As our understanding of the microbiome advances, it is evident that
      these microbial populations participate in a multitude of symbiotic associations
      with us. The disruption of these associations can lead to a range of diseases
      beyond mere pathogenesis as microbial nutrition, signaling, and immune defense
      break down. It is known that changes in microbial composition occur as the human
      host ages and that diet and living conditions influence the microbiome of older
      individuals. However, the link between the microbiome and frailty is as yet
      mostly unexplored. Although the microbiome is likely to influence health factors
      that contribute to frailty, further work is needed to determine whether overall
      microbial signatures of frailty exist and, if so, what the diagnostic and
      therapeutic utility of these signatures might be.

PMID- 26301980
TI  - Operationalizing Frailty Using the Frailty Phenotype and Deficit Accumulation
      Approaches.
AB  - In both demographic and clinical studies, frailty is understood as a
      multidimensional state of increased vulnerability compared with the status of
      others of the same age. Of the many theoretical definitions of frailty, two are
      commonly employed: the physical frailty/phenotypic approach and the deficit
      accumulation approach. The purpose of this chapter is to discuss how frailty is
      conceptualized and operationalized based on these two approaches.

PMID- 26301981
TI  - Comparison and Clinical Applications of the Frailty Phenotype and Frailty Index
      Approaches.
AB  - The previous chapter focused on the conceptualization and operationalization of
      the deficit accumulation and phenotypic approaches to the description of frailty.
      The purpose of this chapter is to summarize some studies that compared these most
      commonly used frailty definitions. We also discuss the strengths and limitations
      of using these two frailty assessments in clinical settings and how they might be
      usefully employed in future studies.

PMID- 26301982
TI  - Frailty in Primary Care.
AB  - This chapter considers the pragmatic integration of frailty in primary care.
      While some patients present to primary care practitioners with relatively well
      defined problems that can be managed by a single intervention and/or organ
      specific specialist referral, others present with nonacute, poorly defined
      problems that are complex and rooted in multiple factors. The latter are often in
      need of a comprehensive geriatric assessment (CGA). CGA can have important
      positive impacts on the health of older people, but it is labor-intensive and
      costly. Therefore, patients at higher risk of adverse outcomes should have higher
      priority to publicly funded CGA services. Frailty is an age-independent marker of
      risk that fits the biopsychosocial model of primary care, and its use (as opposed
      to age alone) may promote equity of access to CGA services. A number of frailty
      assessment tools have been recommended for use in primary care. Some randomized
      controlled trials have shown that frailty screening in primary care, with
      subsequent CGA and intervention, can prevent adverse outcomes. However, this
      result has not been obtained with every screening tool, and comparative trials
      are ongoing. Meanwhile, primary care commissioners in the UK are establishing new
      frailty care pathways and developing frailty registers in primary care.

PMID- 26301983
TI  - Hospital Care for Frail Elderly Adults: From Specialized Geriatric Units to
      Hospital-Wide Interventions.
AB  - Much of the acute care provided in hospitals is for elderly people. Frailty is a
      common clinical condition among these patients. Frail patients are vulnerable to
      undergoing adverse events, to developing geriatric syndromes and to experiencing
      functional decline during or due to hospitalization. The strategy for providing
      specialized geriatric care to these hospitalized frail elderly patients currently
      consists of care provision either by specialized departments or by specialized
      teams who adopt comprehensive geriatric assessment. Even so, financial and human
      resources are insufficient to meet the needs of all hospitalized frail elderly
      patients who require comprehensive geriatric assessment. New innovative and more
      efficient geriatric interventions, in which the priorities of the patients
      themselves should be the main focus, should be developed and implemented, and
      professionals in all specialties should be educated in applying the fundamentals
      of geriatric medicine to their frail elderly patients. In the evaluation of such
      interventions, patient-reported outcomes should play a major role, in addition to
      the more traditional outcome measures of effectiveness, quality of care and cost
      effectiveness.

PMID- 26301984
TI  - Frailty and Mobility.
AB  - Frailty represents a state of heightened vulnerability. Mobility impairment
      contributes to the construct of frailty and channels adverse events. While
      mobility disorder is universal at a high burden of frailty, neither mobility nor
      balance dysfunction is sufficient to fully define frailty. Frailty represents
      proximity to complex system failure, with higher-order disturbance, such as
      mobility and balance disturbance, as a consequence. Impairment of mobility and
      balance is a common manifestation of illness in the frail individual and is
      therefore a sensitive marker of acute disease, putatively also in delirium.
      Clinical measurement of mobility and balance should be prioritized. Consequently,
      assessment tools, such as the de Morton Mobility Index and the Hierarchical
      Assessment of Balance and Mobility, are being explored, with the sensitivity of
      the latter illustrated in the acute hospital setting. Walking with speed and
      under dual/multi-task conditions better differentiates healthier and frail
      ambulant adults, providing a basis for screening older adults for pre-emptive
      interventions. Specific mobility and balance interventions reduce falls risk.
      However, patients with dementia walk too fast for their level of frailty,
      creating an ethical dimension to rehabilitation and risk. Overall, there is no
      need for reduced mobility to reinforce the frailty stereotype; both are
      potentially modifiable and amenable to intervention strategies.

PMID- 26301985
TI  - Frailty and Interprofessional Collaboration.
AB  - This chapter underscores the importance of interprofessional collaboration in the
      care of frail older patients. Hospital-based care is emphasized because
      interprofessionalism is difficult in that setting since the setting is constantly
      changing and since multiple healthcare professionals care for many complex, very
      ill patients, only some of whom are frail older people. Interprofessionalism is
      particularly important and challenging in teaching units in the acute care
      setting, where many health professionals practice and learn together and team
      membership changes frequently. Learning is enhanced and interprofessionalism can
      enhance learning by viewing the patient as a key part of the teaching team. While
      'best practice' interventions have been identified for frail older adults who are
      hospitalized, these interventions are not easily implemented in routine hospital
      care. Three interdependent processes in clinical practice--representation, sense
      making, and improvisation--are described, which contribute to an understanding of
      how practices change when implemented in a way that takes the local context into
      account and keeps person-centered care as the central consideration.

PMID- 26301986
TI  - Frailty and Rehabilitation.
AB  - Rehabilitation approaches to frailty are in the early stages of development.
      Frailty also shows promise as a prognostic indicator for rehabilitation programs,
      similar to its application in other areas of medicine. However, care should be
      taken not to exclude frail older people from rehabilitation, as has been the case
      at some centers for people with cognitive impairment or very severe disability.
      There are clear theoretical reasons to expect that a rehabilitation approach will
      be effective. Some experimental data are also available suggesting that
      rehabilitation is effective in frail and pre-frail older people. The principles
      of a frailty intervention program that have been demonstrated to be clinically
      and economically effective are as follows: first, frailty can be mitigated;
      second, support needs are individually addressed; third, the interventions aim to
      improve physical, cognitive and social functioning; fourth, support has to be
      delivered over a long time period; and finally, systems must facilitate
      consistent management. Most frail older people are encouraged and supported to
      adhere to their intervention plan. It is important to recognize the needs of
      families and/or carers and to engage with them.

PMID- 26301987
TI  - End of Life Care in Frailty.
AB  - The increasing prevalence of frailty within the aging population poses challenges
      to current models of chronic disease management and end-of-life care delivery. As
      frailty progresses, individuals face an increasing frequency of acute health
      issues requiring medical attention. The ability of health care systems to
      recognize and respond to acute health issues in frail patients using a holistic
      understanding of health and prognosis will play a central role in ensuring their
      effective and appropriate care, including that at the end of their lives. This
      chapter reviews the history of palliative care and the elements of frailty that
      require the modification of current models of palliative care. In addition, tools
      and models for recognition of end of life in frailty and considerations for
      symptom management are introduced.

PMID- 26301988
TI  - Frailty and Organization of Health and Social Care.
AB  - In this chapter, we consider how health and social care can best be organized for
      older people with frailty. We will consider the merits of routine frailty
      identification, including risk stratification methods, to inform the provision of
      evidence-based treatment and holistic, goal-oriented care. We will also consider
      how best to place older people with frailty at the heart of health and social
      care systems so that the complex challenges associated with this vulnerable group
      are addressed.

PMID- 26301989
TI  - Frailty's Place in Ethics and Law: Some Thoughts on Equality and Autonomy and on
      Limits and Possibilities for Aging Citizens.
AB  - Consideration of ethical and legal themes relating to frailty must engage with
      the concern that frailty is a pejorative concept that validates and reinforces
      the disadvantage and vulnerability of aging adults. In this chapter, we consider
      whether a greater focus on frailty may indeed be part of the solution to the
      disadvantages that aging adults face in achieving equality and maintaining their
      autonomy within systems that have used their frailty to deny them equality and
      autonomy. First, by examining equality both as an ethical norm and as a
      requirement for protections against discrimination, we raise questions about the
      grounds on which health providers and health systems can be required to give
      equal concern and respect to the needs of frail older persons. Second, we explore
      autonomy and identify the tension between meaningful self-determination and
      prevailing ethical and legal norms associated with informed choice. Third, we
      argue that a proper understanding of frailty is essential within both of these
      themes; it respects equality by enabling health providers and systems to identify
      and address the distinct care needs of aging adults and helps to align informed
      choice theory with appropriate processes for decision-making about those needs.

PMID- 26301990
TI  - Frailty and Social Vulnerability.
AB  - Both intrinsic and extrinsic factors contribute to health. Intrinsic factors are
      familiar topics in health research and include medical conditions, medications,
      genetics and frailty, while extrinsic factors stem from social and physical
      environments. This chapter builds on others in this volume, in which a deficit
      accumulation approach to frailty has been described. The concept of social
      vulnerability is presented. Social vulnerability stems from the accumulation of
      multiple and varied social problems and has bidirectional importance as a risk
      factor for poor health outcomes and as a pragmatic consideration for health care
      provision and planning. Importantly, the social factors that contribute to
      overall social vulnerability come into play at different levels of influence
      (individual, family and friends, peer groups, institutions and society at large).
      A social ecology perspective is discussed as a useful framework for considering
      social vulnerability, as it allows for attention to each of these levels of
      influence. Tying together what we currently understand about frailty (in medical
      and basic science models) and social vulnerability, the scaling potential of
      deficit accumulation is discussed, given that deficit accumulation can be
      understood to occur at many levels, from the (sub-)cellular level to tissues,
      organisms/complex systems and societies.

PMID- 26301991
TI  - Mapping of Quantitative Trait Loci for Contents of Macro- and Microelements in
      Milled Rice (Oryza sativa L.).
AB  - Macro- and microelement contents are important traits for nutritional quality in
      rice. In this study, quantitative trait loci (QTLs) for the contents of seven
      mineral elements in milled rice were detected using recombinant inbred lines
      (RILs) of the indica rice cross Zhenshan 97/Milyang 46, followed by the
      validation and fine mapping of a QTL region on the short arm of chromosome 6. A
      total of 20 QTLs distributed on chromosomes 1, 3, 5, 6, 10, and 11 were detected
      in the RIL population. Co-localizations of QTLs for multiple traits were
      observed, of which the qP3/qMg3/qZn3 region was shown to have the largest effects
      for the contents of phosphorus, magnesium, and zinc, and the
      qK6.1/qCa6/qZn6/qMn6/qCu6 region was found to be responsible for five of the
      seven traits. Using near isogenic lines having sequential segregating region, the
      target QTL on chromosome 6 was delimitated to a 29.9 kb region flanked by RM19410
      and Si2944. This QTL showed major effects for all seven traits, with the
      enhancing alleles derived from the male parent Milyang 46. 

PMID- 26301992
TI  - Depressed scar after filler injection successfully treated with pneumatic
      needleless injector and radiofrequency device.
AB  - Fillers are known to be associated with a number of side effects, one of the most
      severe being skin necrosis. The most vulnerable areas are those that are supplied
      by a single arterial branch; for example, the glabellar and nasolabial folds are
      susceptible. In this study, we report good cosmetic outcomes were produced by
      utilizing the pneumatic needleless injector and radiofrequency device to treat
      depressed scars that occurred after necrosis following filler injection.
      Initially, applying light-emitting diode treatment and following through with the
      two devices appears to have synergistic effects for scar remodeling when dealing
      with treatment of depressed scars with irregular borders. 

PMID- 26301994
TI  - Stone-Wales Rearrangements in Hydrocarbons: From Planar to Bowl-Shaped
      Substrates.
AB  - Carbene, cyclobutyl, and potential diradical mechanisms were studied
      computationally for Stone-Wales rearrangements in several derivatives of as
      indacene and pyracyclene, including cyclopent[hi]acephenanthrylene,
      dicyclopenta[cd,fg]pyrene, corannulene, diindeno[1,2,3,4-defg;1',2',3',4'
      mnop]chrysene, and semibuckminsterfullerene. At the UM06-2X/cc-pVDZ and BD(T)/cc
      pVDZ//UM06-2X/cc-pVDZ levels of theory, free energies of reaction reveal that
      transformations involving an increase in curvature are thermodynamically
      unfavorable. In addition, the carbene transition states or intermediates
      (corrected to 1000  degrees C) are generally around 100-120 kcal/mol higher than
      starting substrates, except for as-indacene (80 kcal/mol), which is the only
      process considered here that is predicted to have a barrier accessible under
      typical flash vacuum pyrolysis conditions. For pyracyclene derivatives, the
      relative free energy of cyclobutyl intermediates rises steadily with increasing
      curvature of the substrate and increasing annelation. Singlet acetylenic
      diradicals related to pyracyclene, diindenochrysene, and semibuckminsterfullerene
      are predicted to be second- or higher-order saddle points that lie more than 40
      kcal/mol higher than the corresponding carbenes and cyclobutyl intermediates. 

PMID- 26301993
TI  - Chrono-immunology: progress and challenges in understanding links between the
      circadian and immune systems.
AB  - Development of inflammatory diseases, such as metabolic syndrome and cancer, is
      prevalent in individuals that encounter continuous disruption of their internal
      clock. Further, daily oscillations in susceptibility to infection as well as a
      multitude of other immunological processes have been described. Much progress has
      been made and various mechanisms have been proposed to explain circadian
      variations in immunity; yet much is still unknown. Understanding the crosstalk
      between the circadian and the immune systems will allow us to manipulate clock
      outputs to prevent and treat inflammatory diseases in individuals at risk. This
      review briefly summarizes current knowledge about circadian rhythms and their
      role in the immune system and highlights progress and challenges in chrono
      immunological research. 

PMID- 26301995
TI  - Peptide-based method for detection of metastatic transformation in primary tumors
      of breast cancer.
AB  - Detection of metastatic activity before the onset of the actual metastasis can be
      a promising method to combat metastasis, the foremost cause of death in cancer.
      Therefore, in this work, we have developed an assay method for the detection of
      metastatic tumor cells in primary tumor, by using a protein of the metastatic
      cell signaling as the biomarker. In this assay, a peptide-based probe targeting
      the marker protein and a sensitive nanoparticle doped graphene nanolabel are
      combined to enable the detection of metastatic cells. Consequently, the
      metastatic cells can be specifically detected and discriminated from primary
      tumor cells. By applying this assay method to clinical samples of primary tumor,
      a low amount of metastatic activity can be detected in the tumor sites, which may
      suggest the activity of local metastatic transformation. So, these results may
      point to the prospect of using the proposed method for controlling metastatic
      cancer. 

PMID- 26301996
TI  - Increase in acrolein-conjugated immunoglobulins in saliva from patients with
      primary Sjogren's syndrome.
AB  - BACKGROUND: We previously reported that the level of protein-conjugated acrolein
      (PC-Acro), a marker of cell or tissue damage, was increased in saliva from
      patients with primary Sjogren's syndrome (pSS), and that the level of PC-Acro was
      well correlated with the severity of pSS. METHODS: Acrolein-conjugated
      immunoglobulins were measured in saliva from pSS patients. RESULTS: The
      activities of autoantibodies recognizing Sjogren's syndrome SSA (Ro) and SSB (La)
      proteins in saliva from pSS patients were approximately 3- to 5-fold higher than
      those from control subjects. We also found that autoantibody activities
      recognizing SSA (Ro) and SSB (La) proteins increased after acrolein treatment of
      saliva from control subjects. When an antibody against human serum albumin was
      treated with acrolein, the ability to recognize albumin was reduced but the
      ability to recognize other proteins was increased. Twenty-four and eleven kinds
      of acrolein-conjugated amino acids were found at the variable and constant
      regions of peptides, respectively, obtained from the immunoglobulins in saliva
      from pSS patients. CONCLUSION: The altered recognition patterns of
      immunoglobulins due to acrolein conjugation are at least partially involved in
      autoimmune diseases.

PMID- 26301998
TI  - Enzyme-triggered formation of enzyme-tyramine concatamers on nanogold
      functionalized dendrimer for impedimetric detection of Hg(II) with sensitivity
      enhancement.
AB  - A new impedimetric sensing strategy based on enzyme-triggered formation of enzyme
      tyramine concatamers on the nanogold-functionalized poly(amidoamine) (PAMAM)
      dendrimer was designed for sensitive detection of mercury(II) (Hg(2+)) ion,
      coupling with enzymatic biocatalytic precipitation towards 4-choloro-1-naphthol
      (4-CN) on thymine (T)-rich single-stranded DNA1-modified electrode. Initially,
      nanogold-decorated PAMAM dendrimer (AuNP-PAMAM) was synthesized by the in-situ
      reduction method, and then functionalized with horseradish peroxidase (HRP) and
      another T-rich oligomer (DNA2). Upon target Hg(2+) introduction, probe DNA2 on
      the AuNP-PAMAM bound to the DNA1 on the electrode owing to the T-Hg(2+)-T
      coordination chemistry between the two DNA strands. Accompanying the AuNP-PAMAM,
      the carried HRP could trigger the formation of HRP-tyramine concatamer via the
      classical tyramine signal amplification strategy in the presence of HRP-tyramine
      conjugates and hydrogen peroxide. The concatenated HRP molecules in the
      concatamer catalyzed the 4-CN oxidation to produce an insoluble precipitation on
      the electrode, thereby resulting in the local alteration in the conductivity.
      Under optimal conditions, two signal-generation tags including HRP-AuNP-DNA2 and
      HRP-AuNP-PAMAM-DNA2 with or without tyramine signal amplification strategy (i.e.,
      four schemes) were used for impedimetric detection of target Hg(2+) on the basis
      of the same assay format. A low detection limit (LOD) of 0.4pM and a wide dynamic
      working range of 0.001-100nM Hg(2+) by using HRP-AuNP-PAMAM-DNA2 with tyramine
      signal amplification strategy were obtained in comparison with those of other
      strategies. The assay had a good repeatability and showed an intermediate
      precision of down to 9.6%. In addition, the methodology also exhibited high
      specificity and selectivity towards target Hg(2+) against other metal ions, and
      was applicable for monitoring Hg(2+) in the spiked drinking water samples. 

PMID- 26301999
TI  - Facile fabrication of an aptasensor for thrombin based on graphitic carbon
      nitride/TiO2 with high visible-light photoelectrochemical activity.
AB  - A novel aptasensor for thrombin with high visible-light activity was facilely
      fabricated based on graphitic carbon nitride/TiO2 (g-C3N4/TiO2)
      photoelectrochemical (PEC) composite. Crystallization of TiO2 nanoparticles (NPs)
      and their strong interaction with g-C3N4 sheet were confirmed by high-resolution
      transmission electron microscope (HR-TEM), both of which contributed to the high
      photocurrent intensity under visible-light irradiation. Carboxyl functionalized
      thrombin aptamers were first successfully bound to the g-C3N4/TiO2 modified
      electrode as proven by photoelectrochemical test and electrochemical impedance
      spectroscopy (EIS) analysis. Ascorbic acid was utilized as the electron donor for
      scavenging photo-generated holes and inhibiting light driven electron-hole pair
      recombination. The specific recognition between thrombin aptamer and thrombin led
      to the linear decrease of photocurrent with the increase of logarithm of thrombin
      concentration in the range of 5.0*10(-13)molL(-1) to 5.0*10(-9)molL(-1) with a
      detection limit of 1.2*10(-13)molL(-1). This proposed low-cost, convenient and
      sensitive aptasensor showed promising applications in biosensor and
      photoelectrochemical analysis. 

PMID- 26301997
TI  - Ubp6 deubiquitinase controls conformational dynamics and substrate degradation of
      the 26S proteasome.
AB  - Substrates are targeted for proteasomal degradation through the attachment of
      ubiquitin chains that need to be removed by proteasomal deubiquitinases before
      substrate processing. In budding yeast, the deubiquitinase Ubp6 trims ubiquitin
      chains and affects substrate processing by the proteasome, but the underlying
      mechanisms and the location of Ubp6 within the holoenzyme have been elusive. Here
      we show that Ubp6 activity strongly responds to interactions with the base ATPase
      and the conformational state of the proteasome. Electron microscopy analyses
      reveal that ubiquitin-bound Ubp6 contacts the N ring and AAA+ ring of the ATPase
      hexamer and is in proximity to the deubiquitinase Rpn11. Ubiquitin-bound Ubp6
      inhibits substrate deubiquitination by Rpn11, stabilizes the substrate-engaged
      conformation of the proteasome and allosterically interferes with the engagement
      of a subsequent substrate. Ubp6 may thus act as a ubiquitin-dependent 'timer' to
      coordinate individual processing steps at the proteasome and modulate substrate
      degradation. 

PMID- 26302000
TI  - A novel electrochemical aptasensor based on arch-shape structure of aptamer
      complimentary strand conjugate and exonuclease I for sensitive detection of
      streptomycin.
AB  - Detection and quantitation of antibiotic residues in blood serum and animal
      foodstuffs are of great significance. In this study, an electrochemical
      aptasensor was developed for sensitive and selective detection of streptomycin,
      based on exonuclease I (Exo I), complimentary strand of aptamer (CS), Arch-shape
      structure of aptamer (Apt)-CS conjugate and gold electrode. The designed
      aptasensor inherits characteristics of gold including large surface area and high
      electrochemical conductivity, as well as high sensitivity and selectivity of
      aptamer toward its target, property of Arch-shape structure of Apt-CS conjugate
      to act as a gate and barrier for the access of redox probe to the surface of
      electrode and the function of Exo I as an enzyme which selectively digests the 3'
      end of single stranded DNA (ssDNA). In the absence of streptomycin the gate
      remains closed. Thus, the electrochemical signal is weak. Upon addition of
      streptomycin, the Apt leaves the CS and binds to streptomycin and the Arch-shape
      structure is disassembled. Then, Exo I addition leads to a strong electrochemical
      signal. The designed electrochemical aptasensor exhibited high selectivity toward
      streptomycin with a limit of detection (LOD) as low as 11.4nM. Moreover, the
      developed electrochemical aptasensor was successfully used to detect streptomycin
      in milk and serum with LODs of 14.1 and 15.3nM, respectively. 

PMID- 26302001
TI  - Using Hamming Distance as Information for SNP-Sets Clustering and Testing in
      Disease Association Studies.
AB  - The availability of high-throughput genomic data has led to several challenges in
      recent genetic association studies, including the large number of genetic
      variants that must be considered and the computational complexity in statistical
      analyses. Tackling these problems with a marker-set study such as SNP-set
      analysis can be an efficient solution. To construct SNP-sets, we first propose a
      clustering algorithm, which employs Hamming distance to measure the similarity
      between strings of SNP genotypes and evaluates whether the given SNPs or SNP-sets
      should be clustered. A dendrogram can then be constructed based on such distance
      measure, and the number of clusters can be determined. With the resulting SNP
      sets, we next develop an association test HDAT to examine susceptibility to the
      disease of interest. This proposed test assesses, based on Hamming distance,
      whether the similarity between a diseased and a normal individual differs from
      the similarity between two individuals of the same disease status. In our
      proposed methodology, only genotype information is needed. No inference of
      haplotypes is required, and SNPs under consideration do not need to locate in
      nearby regions. The proposed clustering algorithm and association test are
      illustrated with applications and simulation studies. As compared with other
      existing methods, the clustering algorithm is faster and better at identifying
      sets containing SNPs exerting a similar effect. In addition, the simulation
      studies demonstrated that the proposed test works well for SNP-sets containing a
      large proportion of neutral SNPs. Furthermore, employing the clustering algorithm
      before testing a large set of data improves the knowledge in confining the
      genetic regions for susceptible genetic markers. 

PMID- 26302003
TI  - Nanoimprint-Assisted Shear Exfoliation (NASE) for Producing Multilayer MoS2
      Structures as Field-Effect Transistor Channel Arrays.
AB  - MoS2 and other semiconducting transition metal dichalcogenides (TMDCs) are of
      great interest due to their excellent physical properties and versatile
      chemistry. Although many recent research efforts have been directed to explore
      attractive properties associated with MoS2 monolayers, multilayer/few-layer MoS2
      structures are indeed demanded by many practical scale-up device applications,
      because multilayer structures can provide sizable electronic/photonic state
      densities for driving upscalable electrical/optical signals. Currently there is a
      lack of processes capable of producing ordered, pristine multilayer structures of
      MoS2 (or other relevant TMDCs) with manufacturing-grade uniformity of thicknesses
      and electronic/photonic properties. In this article, we present a nanoimprint
      based approach toward addressing this challenge. In this approach, termed as
      nanoimprint-assisted shear exfoliation (NASE), a prepatterned bulk MoS2 stamp is
      pressed into a polymeric fixing layer, and the imprinted MoS2 features are
      exfoliated along a shear direction. This shear exfoliation can significantly
      enhance the exfoliation efficiency and thickness uniformity of exfoliated flakes
      in comparison with previously reported exfoliation processes. Furthermore, we
      have preliminarily demonstrated the fabrication of multiple transistors and
      biosensors exhibiting excellent device-to-device performance consistency.
      Finally, we present a molecular dynamics modeling analysis of the scaling
      behavior of NASE. This work holds significant potential to leverage the superior
      properties of MoS2 and other emerging TMDCs for practical scale-up device
      applications. 

PMID- 26302004
TI  - Semantics and cognition.
AB  - The words and grammar of any language encode a vast array of complex prepackaged
      concepts, most of them language-specific and culture-related. These concepts are
      manipulated routinely in almost every waking hour of most people's lives. They
      are largely acquired in infancy and they are intersubjectively shared among
      members of the speech community. It is hard to imagine such elaborate and
      variable representation systems not having a substantial role to play in ordinary
      cognition, and yet the language-and-thought question continues to be a contested
      one across the various disciplines and sub-disciplines of cognitive science. This
      article provides an overview from the vantage point of linguistic semantics.
      WIREs Cogni Sci 2011 2 125-135 DOI: 10.1002/wcs.101 For further resources related
      to this article, please visit the WIREs website. 

PMID- 26302002
TI  - Cwf16p Associating with the Nineteen Complex Ensures Ordered Exon Joining in
      Constitutive Pre-mRNA Splicing in Fission Yeast.
AB  - Exons are ligated in an ordered manner without the skipping of exons in the
      constitutive splicing of pre-mRNAs with multiple introns. To identify factors
      ensuring ordered exon joining in constitutive pre-mRNA splicing, we previously
      screened for exon skipping mutants in Schizosaccharomyces pombe using a reporter
      plasmid, and characterized three exon skipping mutants named ods1 (ordered
      splicing 1), ods2, and ods3, the responsible genes of which encode Prp2/U2AF59,
      U2AF23, and SF1, respectively. They form an SF1-U2AF59-U2AF23 complex involved in
      recognition of the branch and 3' splice sites in pre-mRNA. In the present study,
      we identified a fourth ods mutant, ods4, which was isolated in an exon-skipping
      screen. The ods4+ gene encodes Cwf16p, which interacts with the NineTeen Complex
      (NTC), a complex thought to be involved in the first catalytic step of the
      splicing reaction. We isolated two multi-copy suppressors for the ods4-1
      mutation, Srp2p, an SR protein essential for pre-mRNA splicing, and Tif213p, a
      translation initiation factor, in S. pombe. The overexpression of Srp2p
      suppressed the exon-skipping phenotype of all ods mutants, whereas Tif213p
      suppressed only ods4-1, which has a mutation in the translational start codon of
      the cwf16 gene. We also showed that the decrease in the transcriptional
      elongation rate induced by drug treatment suppressed exon skipping in ods4-1. We
      propose that Cwf16p/NTC participates in the early recognition of the branch and
      3' splice sites and cooperates with the SF1-U2AF59-U2AF23 complex to maintain
      ordered exon joining. 

PMID- 26302005
TI  - Childhood amnesia.
AB  - Childhood amnesia refers to the inability of children and adults to recall events
      that took place during their infancy and early childhood. Freud originally coined
      the term on the basis of clinical interviews; subsequent empirical investigations
      have confirmed many of Freud's original observations, but not his explanation for
      the phenomenon. Consistent with Freud's view, childhood amnesia is not a unitary
      phenomenon, but rather consists of at least two separate phases. In this article,
      we review the evidence for a two-stage phenomenon and highlight some of the major
      developmental changes that might contribute to each phase. We reject Freud's
      repression explanation and argue instead that a comprehensive theory of childhood
      amnesia will require an understanding of neurological, cognitive, language, and
      social development. WIREs Cogni Sci 2011 2 136-145 DOI: 10.1002/wcs.107 For
      further resources related to this article, please visit the WIREs website. 

PMID- 26302006
TI  - Brain asymmetry (animal).
AB  - Once considered a uniquely human attribute, brain asymmetry has been proved to be
      ubiquitous among non-human animals. A synthetic review of evidence of animal
      lateralization in the motor, sensory, cognitive, and affective domains is
      provided, together with a discussion of its development and possible biological
      functions. It is argued that investigation of brain asymmetry in a comparative
      perspective may favor the link between classical neuropsychological studies and
      modern developmental and evolutionary biology approaches. WIREs Cogni Sci 2011 2
      146-157 DOI: 10.1002/wcs.100 For further resources related to this article,
      please visit the WIREs website. 

PMID- 26302007
TI  - Vision in the natural world.
AB  - Historically, the study of visual perception has followed a reductionist
      strategy, with the goal of understanding complex visually guided behavior by
      separate analysis of its elemental components. Recent developments in monitoring
      behavior, such as measurement of eye movements in unconstrained observers, have
      allowed investigation of the use of vision in the natural world. This has led to
      a variety of insights that would be difficult to achieve in more constrained
      experimental contexts. In general, it shifts the focus of vision away from the
      properties of the stimulus toward a consideration of the behavioral goals of the
      observer. It appears that behavioral goals are a critical factor in controlling
      the acquisition of visual information from the world. This insight has been
      accompanied by a growing understanding of the importance of reward in modulating
      the underlying neural mechanisms and by theoretical developments using
      reinforcement learning models of complex behavior. These developments provide us
      with the tools to understanding how tasks are represented in the brain, and how
      they control acquisition of information through use of gaze. WIREs Cogni Sci 2011
      2 158-166 DOI: 10.1002/wcs.113 For further resources related to this article,
      please visit the WIREs website. 

PMID- 26302008
TI  - Game theory.
AB  - Game theory is a toolkit for examining situations where decision makers influence
      each other. I discuss the nature of game-theoretic analysis, the history of game
      theory, why game theory is useful for understanding human psychology, and why
      game theory has played a key role in the recent explosion of interest in the
      field of behavioral economics. WIREs Cogni Sci 2011 2 167-173 DOI:
      10.1002/wcs.119 For further resources related to this article, please visit the
      WIREs website. 

PMID- 26302009
TI  - Neurocognitive mechanisms of action control: resisting the call of the Sirens.
AB  - An essential facet of adaptive and versatile behavior is the ability to
      prioritize actions in response to dynamically changing circumstances. The field
      of potential actions afforded by a situation is shaped by many factors, such as
      environmental demands, past experiences, and prepotent tendencies. Selection
      among action affordances can be driven by deliberate, intentional processes as a
      product of goal-directed behavior and by extraneous stimulus-action associations
      as established inherently or through learning. We first review the neurocognitive
      mechanisms putatively linked to these intention-driven and association-driven
      routes of action selection. Next, we review the neurocognitive mechanisms engaged
      to inhibit action affordances that are no longer relevant or that interfere with
      goal-directed action selection. Optimal action control is viewed as a dynamic
      interplay between selection and suppression mechanisms, which is achieved by an
      elaborate circuitry of interconnected cortical regions (most prominently the pre
      supplementary motor area and the right inferior frontal cortex) and basal ganglia
      structures (most prominently the dorsal striatum and the subthalamic nucleus).
      WIREs Cogni Sci 2011 2 174-192 DOI: 10.1002/wcs.99 For further resources related
      to this article, please visit the WIREs website. 

PMID- 26302010
TI  - Values and preferences: defining preference construction.
AB  - Extensive research in the values and preferences literature suggests that
      preferences are sensitive to context and calculated at the time of choice. This
      has led to the view that preferences are constructed. Recent work calls for a
      better understanding of when preferences are constructed and when they are not.
      We contend that the answer to this question depends on the meaning of the term
      constructed. Constructed can mean that a preference changes across contexts. If
      construction is synonymous with context sensitivity, we contend that preferences
      are always constructed because context influences nearly every aspect of the
      judgment and choice process. As a motivating example, we show that preferences
      are influenced by goals and goals are highly context sensitive. Constructed,
      however, can mean instead that a preference is calculated or formulated during
      the judgment and choice process. If construction is synonymous with calculation,
      we contend that many preferences are calculated and the more important question
      is to what degree preferences are calculated. We review the literature that shows
      that the degree to which decision makers calculate preferences is influenced by
      goals, cognitive constraints, and experience. WIREs Cogni Sci 2011 2 193-205 DOI:
      10.1002/wcs.98 For further resources related to this article, please visit the
      WIREs website. 

PMID- 26302011
TI  - Linguistic evidence and grammatical theory.
AB  - This article surveys the major kinds of empirical evidence used by linguists,
      with a particular focus on the relevance of the evidence to the goals of
      generative grammar. After a background section overviewing the objectives and
      assumptions of that framework, three broad kinds of data are considered in the
      three subsequent sections: corpus data, judgment data, and (other) experimental
      data. The perspective adopted is that all three have their place in the
      linguist's toolbox: they have relative advantages and disadvantages that often
      complement one another, so converging evidence of more than one kind can
      reasonably be sought in many instances. Points are illustrated mainly with
      examples from syntax, but often can be easily translated to other levels (e.g.,
      phonology, morphology, semantics, and pragmatics). WIREs Cogni Sci 2011 2 206-221
      DOI: 10.1002/wcs.102 For further resources related to this article, please visit
      the WIREs website. 

PMID- 26302012
TI  - Stretching the limits of visual attention: the case of action video games.
AB  - Visual attention is the set of mechanisms by which relevant visual information is
      selected while irrelevant information is suppressed, thus allowing the observer
      to function in a world made up of nearly infinite visual information. Recently,
      those who habitually play video games have been documented to outperform novices
      in a variety of visual attentional capabilities, including attention in space, in
      time, and to objects. Training studies have established similar improvements in
      groups of nongamers given experience playing these video games. Critically, not
      all video games seem to have such a beneficial effect on attention; it seems that
      fast-paced, embodied visuo-motor tasks that require divided attention (tasks
      commonly found in popular action games like Halo) have the greatest effect. At
      the core of these action video game-induced improvements appears to be a
      remarkable enhancement in the ability to efficiently deploy endogenous attention.
      The implications of such an enhancement are relevant to a variety of real-world
      applications, such as work force training, rehabilitation of clinical
      populations, and improvement of traditional educational approaches. WIREs Cogni
      Sci 2011 2 222-230 DOI: 10.1002/wcs.116 For further resources related to this
      article, please visit the WIREs website. 

PMID- 26302013
TI  - Dual-systems and the development of reasoning: competence-procedural systems.
AB  - Dual-system, dual-process, accounts of adult cognitive processing are examined in
      the context of a self-organizing relational developmental systems approaches to
      cognitive growth. Contemporary adult dual-process accounts describe a linear
      architecture of mind entailing two split-off, but interacting systems; a domain
      general, content-free 'analytic' system (system 2) and a domain specific highly
      contextualized 'heuristic' system (system 1). In the developmental literature on
      deductive reasoning, a similar distinction has been made between a domain general
      competence (reflective, algorithmic) system and a domain specific procedural
      system. In contrast to the linear accounts offered by empiricist, nativist,
      and/or evolutionary explanations, the dual competence-procedural developmental
      perspective argues that the mature systems emerge through developmental
      transformations as differentiations and intercoordinations of an early relatively
      undifferentiated action matrix. This development, whose microscopic mechanism is
      action-in-the-world, is characterized as being embodied, nonlinear, and
      epigenetic. WIREs Cogni Sci 2011 2 231-237 DOI: 10.1002/wcs.120 For further
      resources related to this article, please visit the WIREs website. 

PMID- 26302014
TI  - Adaptation to sensory loss.

PMID- 26302015
TI  - Alcohol Withdrawal Syndrome: Improving Outcomes Through Early Identification And
      Aggressive Treatment Strategies.
AB  - Alcoholism is a prevalent medical and psychiatric disease, and, consequently,
      alcohol withdrawal is encountered frequently in the emergency department. This
      issue reviews the pathophysiology of the alcohol withdrawal syndrome, describes
      the 4 manifestations of alcohol withdrawal, and looks at the available evidence
      for optimal treatment of alcohol withdrawal in its diverse presentations.
      Patients commonly manifest hyperadrenergic signs and symptoms, necessitating
      admission to the intensive care unit, intravenous benzodiazepines, and,
      frequently, adjunctive pharmacotherapy. An aggressive front-loading approach with
      benzodiazepines is proposed and the management of benzodiazepine-resistant
      disease is addressed.

PMID- 26302016
TI  - Trigeminal neuralgia due to arterialization of the superior petrosal vein in the
      context of dural or cerebral arteriovenous shunt.
AB  - OBJECTIVE: Trigeminal neuralgia (TN) is a rare revealing symptom of dural or
      cerebral arteriovenous (AV) shunt. Few isolated cases have described the
      association between TN and arteriovenous shunt. We presented our experience
      concerning cerebral AV shunt revealed by a TN. METHODS: Between 2003 and 2013,
      548 brain AV malformations (bAVM) and 268 dural AV fistulas (dAVF) were treated
      and a retrospective analysis identified 10 consecutive cases with TN. We reviewed
      their clinical and angiographic data and as well as their outcome after
      endovascular treatment. RESULTS: Among the 10 patients, 5 presented a bAVM and 5
      a dAVF. TN was contralateral to the AV shunt in 2 cases (20%). The superior
      petrosal vein (SPV) was arterialized in all cases. An ectasia of the SPV which
      could explain a compression of the trigeminal nerve was found in two cases only
      (20%). It seems that a venous hyperpressure in the ponto-trigeminal vein
      (tributary of the SPV) is responsible of the TN, rather than a compressive
      mechanism. CONCLUSIONS: Contrary to other publications on this topic, we believe
      that the venous reflux into tributaries of the superior petrous vein (and in
      particular the ponto-trigeminal vein) seems to be the first mechanism of the TN
      rather that the nerve compression.

PMID- 26302017
TI  - Are shunt series and shunt patency studies useful in patients with shunted
      idiopathic intracranial hypertension in the emergency department?
AB  - OBJECTIVES: Shunt series and shunt patency studies can be performed in the
      emergency department (ED) to evaluate for shunt malfunction in patients with
      idiopathic intracranial hypertension (IIH). Here, we examine the utility of these
      studies in this specific patient population. METHODS: We retrospectively reviewed
      the ED visits of all shunted patients diagnosed with IIH from 2003 to 2014. ED
      visits for symptoms not related to the patient's IIH were excluded from the
      study. Collected variables included demographics, symptoms, IIH diagnosis and
      treatment history, imaging findings, and management changes. RESULTS: Twenty-five
      (81%) patients had a total of 105 visits involving a shunt series, with four
      (3.9%) showing problems with the catheter. The majority of shunt series (n=101,
      96%) showed no catheter pathology. Based on results of the shunt series alone, in
      3 instances, management changes in the form of shunt revision or shunt
      reprogramming occurred. Of the 105 visits with a shunt series, 17 (16%) resulted
      in a change in management as compared to 12 out of 66 (18%) visits without a
      shunt series (p=0.83). Nine patients had a total of 10 visits involving a shunt
      patency study: five were normal, four were abnormal, and one was inconclusive.
      Based on findings on the shunt patency study alone, changes in management leading
      to shunt adjustment or revision occurred in 4 instances. Of the 10 visits with
      shunt patency studies, 5 resulted in a change in management as compared to 24 out
      of 161 visits without a shunt patency study (p=0.014). CONCLUSIONS: Shunt series
      detected catheter pathology only 3.9% of the time, and there was no difference in
      the rate of management changes between those patients who underwent a shunt
      series and those who did not. There was a significant difference in the rate of
      management changes in patients who received shunt patency studies as compared to
      those who did not. Shunt series may not be a useful screening tool to be used
      universally to diagnose shunt malfunction in IIH patients in the ED, and should
      be utilized when there is concern for impending visual loss. Shunt patency
      studies should be reserved for patients with inconclusive diagnostic imaging and
      clinical findings to decide whether to proceed to surgical exploration and
      revision.

PMID- 26302019
TI  - Modeling Lipid-Lipid Correlations across a Bilayer Membrane Using the Quasi
      chemical Approximation.
AB  - Mixed fluid-like lipid membranes exhibit interactions not only among the lipids
      within a given leaflet but also across the bilayer. The ensuing collective
      interleaflet coupling of entire membrane domains has been modeled previously
      using various mean-field approaches. Yet, also on the level of individual lipids
      have correlations across the bilayer been observed experimentally for binary
      mixtures of charged/uncharged lipids with mismatching combinations of short and
      long acyl chain lengths. The present study proposes a lattice gas model to
      quantify these correlations. To this end, we represent a macroscopically
      homogeneous lipid bilayer by two coupled two-dimensional lattice gases that we
      study using the quasi-chemical approximation. We demonstrate that the
      rationalization of previous experimental results is only possible if besides two
      body lipid-lipid interactions within and across the bilayer our model also
      accounts for an additional multibody interaction mechanism, namely the local
      hydrophobic height mismatch created by pairing short and long chain lipids
      together. The robustness of the quasi-chemical approximation is verified by
      comparison with Monte Carlo simulations. 

PMID- 26302020
TI  - Specific Drug Formulation Additives: Revealing the Impact of Architecture and
      Block Length Ratio.
AB  - Combining poly(ethylene glycol) (PEG) with sequence-defined peptides in PEG
      peptide conjugates offers opportunities to realize next-generation drug
      formulation additives for overcoming undesired pharmacological profiles of
      difficult small molecule drugs. The tailored peptide segments provide sequence
      specific, noncovalent drug binding, and the hydrophilic PEG block renders the
      complexes water soluble. On the basis of a peptide sequence known to bind the
      photosensitizer m-tetra(hydroxyphenyl)chlorin (m-THPC) for photodynamic cancer
      therapy, a set of different conjugate architectures is synthesized and studied.
      Variations in PEG block length and amplification of the peptidic binding domain
      of PEG-peptide conjugates are used to fine tune critical parameters for hosting m
      THPC, such as drug payload capacities, aggregation sizes, and drug release and
      activation kinetics. 

PMID- 26302018
TI  - Protein-Protein Interactions Mediated by Helical Tertiary Structure Motifs.
AB  - The modulation of protein-protein interactions (PPIs) by means of creating or
      stabilizing secondary structure conformations is a rapidly growing area of
      research. Recent success in the inhibition of difficult PPIs by secondary
      structure mimetics also points to potential limitations, because often, specific
      cases require tertiary structure mimetics. To streamline protein structure-based
      inhibitor design, we have previously described the examination of protein
      complexes in the Protein Data Bank where alpha-helices or beta-strands form
      critical contacts. Here, we examined coiled coils and helix bundles that mediate
      complex formation to create a platform for the discovery of potential tertiary
      structure mimetics. Though there has been extensive analysis of coiled coil
      motifs, the interactions between pre-formed coiled coils and globular proteins
      have not been systematically analyzed. This article identifies critical features
      of these helical interfaces with respect to coiled coil and other helical PPIs.
      We expect the analysis to prove useful for the rational design of modulators of
      this fundamental class of protein assemblies. 

PMID- 26302021
TI  - How Will Climate Warming Affect Non-Native Pumpkinseed Lepomis gibbosus
      Populations in the U.K.?
AB  - Of the non-native fishes introduced to the U.K., the pumpkinseed is one of six
      species predicted to benefit from the forecasted climate warming conditions. To
      demonstrate the potential response of adults and their progeny to a water
      temperature increase, investigations of parental pumpkinseed acclimatization,
      reproduction and YOY over-wintering were carried out in outdoor experimental
      ponds under ambient and elevated water temperature regimes. No temperature
      effects were observed on either adult survivorship and growth, and none of the
      assessed reproductive activity variables (total spawning time, spawning season
      length, number of spawning bouts) appeared to be responsible for the large
      differences observed in progeny number and biomass. However, it was demonstrated
      in a previous study [Zieba G. et al., 2010] that adults in the heated ponds began
      spawning earlier than those of the ambient ponds. Ambient ponds produced 2.8*
      more progeny than the heated ponds, but these progeny were significantly smaller,
      probably due to their late hatching date, and subsequently suffered very high
      mortality over the first winter. Pumpkinseed in the U.K. will clearly benefit
      from climate warming through earlier seasonal reproduction, resulting in larger
      progeny going into winter, and as a result, higher over-winter survivorship would
      be expected relative to that which occurs under the present climatic regime. 

PMID- 26302022
TI  - Location, Partitioning Behavior, and Interaction of Capsaicin with Lipid Bilayer
      Membrane: Study Using Its Intrinsic Fluorescence.
AB  - Capsaicin is an ingredient of a wide variety of red peppers, and it has various
      pharmacological and biological applications. The present study explores the
      interaction of capsaicin with dimyristoylphosphatidylcholine (DMPC) lipid bilayer
      membrane by monitoring various photophysical parameters using its intrinsic
      fluorescence. In order to have a clearer understanding of the photophysical
      responses of capsaicin, studies involving (i) its solvation behavior in different
      solvents, (ii) the partition coefficient of capsaicin in different thermotropic
      phase states of lipid bilayer membrane, and (iii) its location inside lipid
      bilayer membrane have been carried out. Capsaicin has a reasonably high partition
      coefficient for DMPC liposome membrane, in both solid gel (2.8 +/- 0.1 * 10(5))
      and liquid crystalline (2.6 +/- 0.1 * 10(5)) phases. Fluorescence quenching study
      using cetylpyridinium chloride (CPC) as quencher suggests that the phenolic group
      of capsaicin molecule is generally present near the headgroup region and
      hydrophobic tail present inside hydrophobic core region of the lipid bilayer
      membrane. The intrinsic fluorescence intensity and lifetime of capsaicin
      sensitively respond to the temperature dependent phase changes of liposome
      membrane. Above 15 mol %, capsaicin in the aqueous liposome suspension medium
      lowers the thermotropic phase transition temperature by about 3  degrees C, and
      above 30 mol %, the integrity of the membrane is significantly lost. 

PMID- 26302023
TI  - Comparative diagnostic accuracy of red cell distribution width-to-platelet ratio
      versus noninvasive fibrosis scores for the diagnosis of liver fibrosis in biopsy
      proven nonalcoholic fatty liver disease.
AB  - OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease
      and assessment of liver fibrosis is important. We aimed to investigate the
      performance of red cell volume distribution width-to-platelet ratio (RPR) in
      predicting liver fibrosis in patients with NAFLD and to compare it with well
      known noninvasive predicting fibrosis scores (alanine aminotransferase ratio,
      aspartate aminotransferase platelet ratio index, fibrosis index, fibrosis 4, and
      fibrosis, cirrhosis index). MATERIALS AND METHODS: Serum samples of consecutive
      biopsy-proven NAFLD patients were used to calculate the RPR index. Fibrosis
      stages were evaluated using the Brunt Criteria. Area under receiver operating
      characteristics curve was used to calculate predicting performance and compare
      with other noninvasive fibrosis scores. RESULTS: One hundred and twenty-three
      consecutive patients with biopsy-confirmed NAFLD were recruited; 54 patients
      (43.9%) were women. The median age of the patients was 49 years. Fibrosis scores
      were F0-1, F2, F3, and F4 in 79 (64.2%), 27 (22%), 11 (8.9%), and 6 (4.9%)
      patients, respectively. The median RPR increased as the fibrosis scores
      progressed: F0, 0.0524; F1, 0.0534; F2, 0.0606; F3, 0.0815; and F4 0.2022. Area
      under receiver operating characteristics curve of the RPR was 0.69 in predicting
      significant fibrosis (>= F2), 0.81 in advanced fibrosis (>= F3), and 0.85 in F4,
      and all were statistically significant (P<0.001). Comparisons with other
      noninvasive fibrosis scores were not statistically significant (P>0.05). RPR was
      correlated with fibrosis r: 0.37, 95% confidence interval: (0.21-0.52), P<0.001.
      RPR was an independent predicting factor for identifying both significant and
      advanced fibrosis in regression analysis (P<0.05). CONCLUSION: RPR was both
      correlated and able to predict liver fibrosis and may be suggested to reduce
      liver biopsy in NAFLD.

PMID- 26302025
TI  - Effect of magic angle spinning on (13)C spin-lattice and spin-spin relaxation in
      nanodiamonds.
AB  - We report on (13)C spin-lattice (R 1) and spin-spin (R 2) relaxation rate
      dependence on magic-angle-spinning (MAS) rate in highly purified synthetic
      nanodiamonds. Noticeable slowdown of both relaxation processes and reduction of
      nuclear spin diffusion coefficient D with increasing MAS rate was obtained. This
      effect is attributed to suppression of nuclear spin diffusion by MAS. We
      developed a theoretical approach that describes the MAS rate dependence of R 1, R
      2 and D, allows quantitative analysis of the data and shows good compliance with
      the experiment. 

PMID- 26302024
TI  - Effects of probiotics (cultured Lactobacillus subtilis/Streptococcus faecium) in
      the treatment of alcoholic hepatitis: randomized-controlled multicenter study.
AB  - BACKGROUND: Probiotics might reduce gut-derived microbial lipopolysaccharide
      (LPS) by restoring bowel flora in patients with alcoholic hepatitis (AH). We
      evaluated the therapeutic effects of probiotics in patients with AH. PATIENTS AND
      METHODS: Between September 2010 and April 2012, 117 patients (probiotics 60 and
      placebo 57) were prospectively randomized to receive the 7 days of cultured
      Lactobacillus subtilis/Streptococcus faecium (1500 mg/day) or placebo. All
      patients were hospitalized and were not permitted to consume alcohol for the 7
      days of the study. Liver function test, proinflammatory cytokines, LPS, and
      colony-forming units by stool culture were examined and compared after therapy.
      RESULTS: In both groups, the mean levels of aspartate aminotransferase/alanine
      aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, bilirubin,
      and prothrombin time were significantly improved after 7 days of abstinence. In
      the probiotics group (baseline and after), albumin (3.5 +/- 0.7 and 3.7 +/- 0.6
      g/dl, P=0.038) and tumor necrosis factor-alpha (121 +/- 244 and 71 +/- 123 pg/ml,
      P=0.047) showed differences. In addition, the number of colony-forming units of
      Escherichia coli was significantly reduced (435 +/- 287 and 168 +/- 210,
      P=0.002). In the placebo group, the level of LPS (1.7 +/- 2.8 and 2.0 +/- 2.7
      EU/ml) was significantly increased. In the intergroup comparison, significant
      differences in the levels of tumor necrosis factor-alpha (P=0.042) and LPS
      (P=0.028) were observed between the groups. CONCLUSION: Immediate abstinence is
      the most important treatment for patients with AH. In addition, 7 days of oral
      supplementation with cultured L. subtilis/S. faecium was associated with
      restoration of bowel flora and improvement of LPS in patients with AH.

PMID- 26302026
TI  - Prevalence of Prediabetes Based on Fasting Plasma Glucose and Glycosylated
      Hemoglobin in an At-Risk Mexican Population.
AB  - BACKGROUND: In Latin America, there are no published studies of the prevalence of
      prediabetes using the glycosylated hemoglobin (HbA1c) criterion in addition to
      fasting plasma glucose (FPG). Therefore, here we determined the prevalence of
      prediabetes using FPG and/or HbA1c in a Mexican population at risk for type 2
      diabetes mellitus (T2DM) and cardiovascular disease. METHODS: This cross
      sectional study included 384 primary care users without a known diagnosis of
      prediabetes or T2DM and with at least one risk factor for T2DM and cardiovascular
      disease. An FPG 100-125 mg/dL and/or an HbA1c 5.7-6.4% were considered positive
      for prediabetes. Point prevalence and 95% confidence intervals (CI) were
      estimated overall and stratified by age, sex, and nutritional status. Mann
      Whitney and chi-squared tests were used. P values < 0.05 were considered
      significant. RESULTS: The prevalence of prediabetes was 74.7% (95% CI, 70.2%
      78.8%) using FPG or HbA1c criteria for positivity, 60.4% using FPG alone (95% CI,
      55.5%-65.3%), 49.8% using HbA1c alone (95% CI, 44.4-55.3%); and 32.9% using FPG
      and HbA1c (95% CI, 27.8%-38.0%). Prevalence was higher in patients >=50 years old
      (p < 0.001) and in the overweight-obesity group (p = 0.04) using all criteria
      except for HbA1c alone. CONCLUSIONS: The prevalence of prediabetes in a Mexican
      population at risk for cardiovascular disease and/or T2DM was high. Prediabetes
      is definitely a public health problem. Future studies are needed to examine the
      effectiveness and efficiency of pragmatic strategies to reverse the status of
      prediabetes and, therefore, reduce the incidence of T2DM.

PMID- 26302027
TI  - Preservation of memory-based automaticity in reading for older adults.
AB  - Concerning age-related effects on cognitive skill acquisition, the modal finding
      is that older adults do not benefit from practice to the same extent as younger
      adults in tasks that afford a shift from slower algorithmic processing to faster
      memory-based processing. In contrast, Rawson and Touron (2009) demonstrated a
      relatively rapid shift to memory-based processing in the context of a reading
      task. The current research extended beyond this initial study to provide more
      definitive evidence for relative preservation of memory-based automaticity in
      reading tasks for older adults. Younger and older adults read short stories
      containing unfamiliar noun phrases (e.g., skunk mud) followed by disambiguating
      information indicating the combination's meaning (either the normatively dominant
      meaning or an alternative subordinate meaning). Stories were repeated across
      practice blocks, and then the noun phrases were presented in novel sentence
      frames in a transfer task. Both age groups shifted from computation to retrieval
      after relatively few practice trials (as evidenced by convergence of reading
      times for dominant and subordinate items). Most important, both age groups showed
      strong evidence for memory-based processing of the noun phrases in the transfer
      task. In contrast, older adults showed minimal shifting to retrieval in an
      alphabet arithmetic task, indicating that the preservation of memory-based
      automaticity in reading was task-specific. Discussion focuses on important
      implications for theories of memory-based automaticity in general and for
      specific theoretical accounts of age effects on memory-based automaticity, as
      well as fruitful directions for future research.

PMID- 26302028
TI  - Hope for the best, prepare for the worst? Future self-views and preparation for
      age-related changes.
AB  - Extending research on the impact of views on aging and developmental regulation
      across the life span, we tested the hypothesis that more positive views of
      oneself as an older person predict more preparation for age-related changes.
      Drawing on recent evidence regarding the domain specificity of aging-related
      developmental processes, we assumed this relationship to be moderated by the
      relevance of preparation in different life domains for different age groups. We
      investigated these research questions in a longitudinal study that assessed
      future self-views and preparation for different life domains in a sample covering
      a large part of the adult life span. Findings supported our hypotheses: More
      positive/negative personal views of one's own aging at T1 predicted subsequent
      increases/decreases in preparation, with influences being strongest for those
      domains in which relevant age-related changes are expected to occur for the
      respective age groups. Our study provides additional evidence for the idea that
      views on aging shape development, identifying age-related provision making as an
      important mediating process. Furthermore, our findings highlight the added value
      of a domain-specific approach that takes the differential relevance of life
      domains and age-related developmental tasks into account.

PMID- 26302029
TI  - Single-dose toxicokinetics of permethrin in broiler chickens.
AB  - Single-dose toxicokinetics of permethrin was investigated in broiler chickens. A
      total of 20 male broiler chickens were assigned at random to two groups of 10 at
      30 days of age. A single dose of 10 mg/kg body weight of permethrin was
      administered intravenously to the first group; in the second group, the same dose
      was administered into the crop. Serum permethrin was measured using an electron
      capture detector and gas chromatography equipment. The derived serum permethrin
      concentration/time curve demonstrated that the distribution kinetics of
      permethrin was well described by a two-compartment open model. For intravenous
      permethrin administration, the half-life at lambda phase (t1/2lambda), mean
      residence time (MRT) and area under the concentration-time curve in 0->infinity
      (AUC0->infinity) values respectively were 4.73 +/- 1.00 h, 5.06 +/- 1.05 h and
      16.45 +/- 3.28 mg/h/l. In contrast, the Cmax, tmax, t1/2lambda, MRT and AUC0
      >infinity values respectively of the group given intra-crop permethrin were 0.60
      +/- 0.42 MUg/ml, 0.55 +/- 0.19 h, 5.54 +/- 0.78 h, 7.06 +/- 0.63 h and 1.95 +/-
      0.97 mg/h/l. The bioavailability of permethrin was 0.11. For both administration
      routes, the residence time of permethrin in the body was short and the
      bioavailability of permethrin was low. These results are relevant for assessing
      the use and safety of permethrin. 

PMID- 26302030
TI  - A Self-Assembled, Low-Cost, Microstructured Layer for Extremely Stretchable Gold
      Films.
AB  - We demonstrate a simple, low-cost, and green approach to deposit a
      microstructured coating on the silicone elastomer polydimethylsiloxane (PDMS)
      that can be coated with gold to produce highly stretchable and conductive films.
      The microstructured coating is fabricated using an aqueous emulsion of poly(vinyl
      acetate) (PVAc): common, commercially available white glue. The aqueous glue
      emulsion self-assembles on the PDMS surface to generate clustered PVAc globules,
      which can be conformally coated with gold. The microstructured surface provides
      numerous defect sites that localize strain when the structure is stretched,
      resulting in the initiation of numerous microcracks. As the structure is further
      elongated, the microcracks interact with one another, preventing long-range crack
      propagation and thus preserving the conduction pathway. The resistance of
      PDMS/glue/gold structures remains remarkably low (23 times the initial
      resistance) up to 65% elongation, making these structure useful as stretchable
      interconnects. Decreasing the concentration of the PVAc aqueous emulsion reduces
      the density of defect sites of the microstructure, which increases the change in
      resistance of the gold films with stretching. In this way, we can tune the
      resistance changes of the PDMS/glue/gold structures and increase their
      sensitivity to strain. We demonstrate the use of these structures as wearable,
      soft strain sensors. 

PMID- 26302031
TI  - Heparin induced thrombocytopenia. Contemporary therapeutic approaches in light of
      the new oral anticoagulants.
AB  - Heparin induced thrombocytopenia (HIT) is a prothrombotic syndrome initiated by
      platelet-activating auto-antibodies with potentially devastating complications.
      Once the diagnosis of HIT is suspected, discontinuation of heparin and treatment
      with an alternative anticoagulant are mandatory. While established drugs for HIT
      are no longer available, parenteral factor Xa inhibitors, thrombin inhibitors and
      perhaps the direct oral anticoagulants provide additional treatment options. The
      aim of this review was to highlight the current clinical aspects regarding HIT
      focusing on the role of novel medications. 

PMID- 26302032
TI  - Intravitreal Anti-VEGF Injections in Pregnancy: Case Series and Review of
      Literature.
AB  - The use of intravitreal antivascular endothelial growth factor (anti-VEGF)
      injection is gaining wide acceptance as an off-label therapy for diseases that
      may affect pregnant women. However, these drugs may cause systemic side effects
      in the mother and fetal harm. This could lead specialists to not administer the
      drug or women to abort the fetus or to refuse treatment during pregnancy. We
      report the course of pregnancy in 3 women treated with intravitreal bevacizumab
      and provide a review of the literature on the use of intravitreal anti-VEGF in
      pregnancy. Our patients did not have any drug-related adverse event and delivered
      healthy full-term infants, although one of the women had risk factors for
      miscarriage. Infants reached all developmental milestones appropriately during
      infancy. A literature search on the use of intravitreal anti-VEGF injection in
      pregnancy was undertaken. Data for this review were identified by searches of
      PubMed and references from relevant articles using the search terms "pegaptanib,"
      "bevacizumab," "ranibizumab," "aflibercept," "anti-VEGF," "intravitreal
      injection," "pregnant," "pregnancy," "abortion," "miscarriage," "preeclampsia,"
      "embryo-fetal toxicity," "fetal malformations," "teratogenesis," "adverse
      events," and "maternofetal complications" in multiple combinations. We believe
      that intravitreal anti-VEGF can be given during pregnancy only when potential
      benefit to the woman justifies the potential risks to the fetus. When making a
      decision about whether to give drugs during pregnancy, it is important to
      consider the timing of exposure and its relationship to windows of developmental
      sensitivity. We believe that this review will be useful to specialists to inform
      and possibly treat their pregnant patients. 

PMID- 26302033
TI  - Bovine Oviduct Epithelial Cells Dedifferentiate Partly in Culture, While
      Maintaining their Ability to Improve Early Embryo Development Rate and Quality.
AB  - There are convincing arguments to suggest that the success of early reproductive
      events is reliant on a satisfactory dialogue between gametes-embryo and the
      oviduct epithelium. The aim of this study was to develop and characterize an in
      vitro model to study these interactions. Cattle zygotes produced in vitro were
      cultured in either SOF or TCM-199 in the presence or absence of bovine oviduct
      cell monolayers (BOEC), under 20% or 5% O2 . The embryonic development rate and
      its quality (cell numbers, cryosurvival) were evaluated, as were the BOEC
      contents in 11 candidate transcripts (real-time PCR) at different time points. A
      BOEC co-culture did indeed increase the rate of development in both media under
      5% O2 (41 vs 27% and 28 vs 10% of Day 8 blastocysts in SOF and TCM-199,
      respectively; p < 0.05). The effect of BOEC on the developmental rate was more
      pronounced under 20% O2 (35 vs 6% and 27 vs 4% of Day 8 blastocysts in SOF and
      TCM-199, respectively; p < 0.05). BOEC significantly increased the embryonic cell
      count in TCM-199 (122.5 +/- 11.1 vs 70.3 +/- 9.6; p < 0.05) and embryonic
      cryosurvival in both media. The expression levels of SOD, FGF2 and TGF-beta1 in
      BOEC remained steady during culture, although mRNA levels of OGP, C3, PGR and
      ESR2 were clearly reduced, suggesting a dedifferentiation of BOEC during culture.
      However, SSP1 and GPX4 transcripts were slightly increased during culture, this
      rise becoming significant by the end of the culture period. In conclusion, our co
      culture system with bovine oviduct epithelial cells used for the development of
      bovine zygotes produced in vitro enhanced blastocyst formation and above all the
      quality of the resulting embryos, which was associated with specific
      transcriptomic changes. 

PMID- 26302034
TI  - A low-fat yoghurt supplemented with a rooster comb extract on muscle joint
      function in adults with mild knee pain: a randomized, double blind, parallel,
      placebo-controlled, clinical trial of efficacy.
AB  - Preliminary results suggested that oral-administration of rooster comb extract
      (RCE) rich in hyaluronic acid (HA) was associated with improved muscle strength.
      Following these promising results, the objective of the present study was to
      evaluate the effect of low-fat yoghurt supplemented with RCE rich in HA on muscle
      function in adults with mild knee pain; a symptom of early osteoarthritis.
      Participants (n = 40) received low-fat yoghurt (125 mL d(-1)) supplemented with
      80 mg d(-1) of RCE and the placebo group (n = 40) consumed the same yoghurt
      without the RCE, in a randomized, controlled, double-blind, parallel trial over
      12 weeks. Using an isokinetic dynamometer (Biodex System 4), RCE consumption,
      compared to control, increased the affected knee peak torque, total work and mean
      power at 180 degrees  s(-1), at least 11% in men (p < 0.05) with no differences
      in women. No dietary differences were noted. These results suggest that long-term
      consumption of low-fat yoghurt supplemented with RCE could be a dietary tool to
      improve muscle strength in men, associated with possible clinical significance.
      However, further studies are needed to elucidate reasons for these sex difference
      responses observed, and may provide further insight into muscle function. 

PMID- 26302035
TI  - Feeding dried distillers grains with solubles to lactating beef cows: impact of
      excess protein and fat on cow performance, milk production and pre-weaning
      progeny growth.
AB  - Multiparous Angus*Simmental cows (n=54, 5.22+/-2.51 years) with male progeny were
      fed one of two diets supplemented with either dried distillers grains with
      solubles (DDGS) or soybean meal (CON), from calving until day 129 postpartum (PP)
      to determine effects of excess protein and fat on cow performance, milk
      composition and calf growth. Diets were formulated to be isocaloric and consisted
      of rye hay and DDGS (19.4% CP; 8.76% fat), or corn silage, rye hay and soybean
      meal (11.7% CP; 2.06% fat). Cow-calf pairs were allotted by cow and calf age, BW
      and breed. Cow BW and body condition score (BCS; P?0.13) were similar throughout
      the experiment. A weigh-suckle-weigh was performed on day 64 and day 110+/-10 PP
      to determine milk production. Milk was collected on day 68 and day 116+/-10 PP
      for analysis of milk components. Milk production was unaffected (P?0.75) by
      dietary treatments. Milk urea nitrogen was increased at both time points in DDGS
      compared with CON cows (P<0.01). Protein was decreased (P=0.01) and fat was
      increased (P=0.01) in milk from DDGS compared with CON cows on day 68 PP.
      Compared to CON, DDGS decreased medium chain FA (P<0.01) and increased long chain
      FA (P<0.01) at both time points. Saturated FA content of milk was decreased
      (P<0.01) at both time-points in DDGS compared with CON cows, which resulted in an
      increase (P<0.01) in monounsaturated and polyunsaturated FA, including cis-9,
      trans-11 conjugated linoleic acid. Daily gain of the DDGS calves was increased
      (P=0.01) compared with CON calves, resulting in heavier BW on day 129 (P=0.01).
      Heavier BW of DDGS calves was maintained through weaning (P=0.01). Timed
      artificial insemination (TAI) rates were greater for cows fed DDGS compared with
      cows fed CON (P<0.02), but dietary treatment had no effect on overall pregnancy
      rates (P=0.64). In summary, feeding DDGS to lactating beef cows did not change
      cow BW or BCS, but did improve TAI rates and altered milk composition compared
      with CON. As a result, male progeny from cows fed DDGS during lactation had
      greater average daily gain and were heavier at day 129 and at weaning compared
      with male progeny from cows fed a control diet. 

PMID- 26302036
TI  - Imidazolium-Based Ionic Liquids in Water: Assessment of Photocatalytic and
      Photochemical Transformation.
AB  - The photoinduced transformation of two ionic liquids, 1-methylimidazolium
      hydrogensulfate (HMIM) and 1-ethyl-3-methylimidazolium hydrogensulfate (EMIM),
      was investigated under photocatalytic conditions in the presence of irradiated
      TiO2. We monitored substrate disappearance, transformation products (TPs), degree
      of mineralization, and toxicity of the irradiated systems. Acute toxicity
      measures suggested in both cases the occurrence of more toxic TPs than the parent
      molecules. A total of five TPs were detected by HPLC-HRMS from HMIM and nine from
      EMIM. Complete mineralization and stoichiometric release of nitrogen was achieved
      for both compounds within 4 h of irradiation. The photochemical transformation
      kinetics and pathways in surface waters (direct photolysis and indirect
      photoreactions) were studied for EMIM, to assess its persistence in sunlit water
      bodies such as rivers or lakes. Environmental phototransformation would be
      dominated by direct photolysis, with half-life times of up to one month under
      fine-weather conditions. 

PMID- 26302037
TI  - 3D interslab echo-shifted FLASH sequence for susceptibility weighted imaging.
AB  - PURPOSE: To develop a novel three-dimensional (3D) sequence for susceptibility
      weighted imaging that is able to reduce scan time substantially while maintaining
      high image signal-to-noise ratio (SNR). METHODS: The proposed fast T2 *-weighted
      sequence was based on a 3D full-balanced gradient frame and a pair of crusher
      gradients. The pair of crusher gradients were used to shift MR signal from the
      repetition time where the MR signal was originated to a later repetition time to
      enhance T2 * weighting. To avoid image SNR reduction due to the repeated signal
      excitations by later RF pulses, as it would occur for typical echo-shifted (ES)
      FLASH, an interslab scan mode for the fast T2 *-weighted sequence was introduced
      for signal acquisition. The effectiveness of this novel sequence was evaluated by
      comparing it with 3D FLASH and ES-FLASH sequences. RESULTS: The proposed
      interslab ES T2 *-weighted sequence was able to reduce the scan time by half with
      a SNR comparable to the typical multislab FLASH. Besides, it yielded a higher
      image SNR than the traditional multislab ES-FLASH and was more flexible than the
      whole-volume ES-FLASH. CONCLUSION: An interslab ES sequence was developed with
      high time efficiency and relatively high image SNR compared with the conventional
      acquisition sequences. Magn Reson Med 76:222-228, 2016. (c) 2015 Wiley
      Periodicals, Inc.

PMID- 26302038
TI  - Isolation of oxalotrophic bacteria associated with Varroa destructor mites.
AB  - Bacteria associated with varroa mites were cultivated and genotyped by 16S RNA.
      Under our experimental conditions, the cultivable bacteria were few in number,
      and most of them proved to be fastidious to grow. Cultivation with seven
      different media under O2 /CO2 conditions and selection for colony morphology
      yielded a panel of species belonging to 13 different genera grouped in two
      different phyla, proteobacteria and actinobacteria. This study identified one
      species of actinobacteria that is a known commensal of the honey bee. Some
      isolates are oxalotrophic, a finding that may carry ramifications into the use of
      oxalic acid to control the number of phoretic mites in the managed colonies of
      honey bees. SIGNIFICANCE AND IMPACT OF THE STUDY: Oxalic acid, legally or brevi
      manu, is widely used to control phoretic Varroa destructor mites, a major drive
      of current honey bees' colony losses. Unsubstantiated by sanctioned research are
      rumours that in certain instances oxalic acid is losing efficacy, forcing
      beekeepers to increase the frequency of treatments. This investigation fathoms
      the hypothesis that V. destructor associates with bacteria capable of degrading
      oxalic acid. The data show that indeed oxalotrophy, a rare trait among bacteria,
      is common in bacteria that we isolated from V. destructor mites. This finding may
      have ramifications in the use of oxalic acid as a control agent.

PMID- 26302039
TI  - Durometry as an outcome measure in juvenile localized scleroderma.

PMID- 26302040
TI  - Sample size methods for estimating HIV incidence from cross-sectional surveys.
AB  - Understanding HIV incidence, the rate at which new infections occur in
      populations, is critical for tracking and surveillance of the epidemic. In this
      article, we derive methods for determining sample sizes for cross-sectional
      surveys to estimate incidence with sufficient precision. We further show how to
      specify sample sizes for two successive cross-sectional surveys to detect changes
      in incidence with adequate power. In these surveys biomarkers such as CD4 cell
      count, viral load, and recently developed serological assays are used to
      determine which individuals are in an early disease stage of infection. The total
      number of individuals in this stage, divided by the number of people who are
      uninfected, is used to approximate the incidence rate. Our methods account for
      uncertainty in the durations of time spent in the biomarker defined early disease
      stage. We find that failure to account for this uncertainty when designing
      surveys can lead to imprecise estimates of incidence and underpowered studies. We
      evaluated our sample size methods in simulations and found that they performed
      well in a variety of underlying epidemics. Code for implementing our methods in R
      is available with this article at the Biometrics website on Wiley Online Library.

PMID- 26302042
TI  - Dual-Enhanced Photocatalytic Activity of Fe-Deposited Titanate Nanotubes Used for
      Simultaneous Removal of As(III) and As(V).
AB  - Fe-deposited titanate nanotubes (Fe-TNTs) with high photocatalytic activity and
      adsorptive performance were synthesized through a one-step hydrothermal method.
      Initial As(III) oxidation followed by As(V) adsorption by Fe-TNTs could
      simultaneously remove these two toxic pollutants from aqueous solutions. The
      apparent rate constant value for photo-oxidation of As(III) under UV irradiation
      by Fe-TNTs was almost 250 times that of unmoidified TNTs. Under visible light,
      the Fe-TNTs also exhibited enhanced photocatalytic activity after Fe was
      deposited. Fe3+ located in the interlayers of TNTs acted as temporary electron-
      or hole-trapping sites, and attached alpha-Fe2O3 played the role of a charge
      carrier for electrons transferred from TNTs. These two effects inhibited electron
      hole pair recombination thus promoting photocatalysis. Moreover, the As(V)
      adsorptive performance of Fe-TNTs also improved, owing to the presence of
      additional adsorption sites, alpha-Fe2O3, as well as increased pHPZC.
      Furthermore, Fe-TNTs exhibited good photocatalytic and adsorptive performace even
      after 5 reuse cycles. The present tests, concerning an initial As(III)
      photocatalysis and subsequent As(V) adsorption process, highlight the feasibility
      and importance of Fe used to modify TNTs. This study proposes a feasible method
      to simultaneously remove As(III) and As(V) from contaminated water using a novel
      Ti-based nanomaterial.

PMID- 26302041
TI  - The Peanut (Arachis hypogaea L.) Gene AhLPAT2 Increases the Lipid Content of
      Transgenic Arabidopsis Seeds.
AB  - Lysophosphatidic acid acyltransferase (LPAT), which converts lysophosphatidic
      acid (LPA) to phosphatidic acid (PA), catalyzes the addition of fatty acyl
      moieties to the sn-2 position of the LPA glycerol backbone in triacylglycerol
      (TAG) biosynthesis. We recently reported the cloning and temporal-spatial
      expression of a peanut (Arachis hypogaea) AhLPAT2gene, showing that an increase
      in AhLPAT2 transcript levels was closely correlated with an increase in seed oil
      levels. However, the function of the enzyme encoded by the AhLPAT2 gene remains
      unclear. Here, we report that AhLPAT2 transcript levels were consistently higher
      in the seeds of a high-oil cultivar than in those of a low-oil cultivar across
      different seed developmental stages. Seed-specific overexpression of AhLPAT2 in
      Arabidopsis results in a higher percentage of oil in the seeds and greater-than
      average seed weight in the transgenic plants compared with the wild-type plants,
      leading to a significant increase in total oil yield per plant. The total fatty
      acid (FA) content and the proportion of unsaturated FAs also increased. In the
      developing siliques of AhLPAT2-overexpressing plants, the expression levels of
      genes encoding crucial enzymes involved in de novo FA synthesis, acetyl-CoA
      subunit (AtBCCP2) and acyl carrier protein 1 (AtACP1) were elevated. AhLPAT2
      overexpression also promoted the expression of several key genes related to TAG
      assembly, sucrose metabolism, and glycolysis. These results demonstrate that the
      expression of AhLPAT2 plays an important role in glycerolipid production in
      peanuts. 

PMID- 26302045
TI  - Current Trends, Evaluation, and Management of Pediatric Nephrolithiasis.
AB  - The incidence of pediatric nephrolithiasis has been steadily increasing for the
      past several decades, with a concomitant concerning increase in health care costs
      and burden to children with this disease. Recent population-based studies have
      also demonstrated a change in the current trends of pediatric nephrolithiasis
      that is characterized by a significant increase in the number of girls now being
      affected. While changes in diet and lifestyle, obesity prevalence, and even
      imaging practices have been proposed to contribute to the recent increase in
      pediatric nephrolithiasis, a definite underlying cause remains elusive. This
      situation is complicated by the fact that, unlike in adults, the trends occurring
      in pediatric nephrolithiasis have not been studied rigorously, which contributes
      to the paucity of data in children. The level of concern with the increasing
      incidence is raised by factors unique to pediatric nephrolithiasis that could
      expose an affected child to more complications. Factors such as variable clinical
      presentation, high recurrence of kidney stones associated with abnormalities of
      metabolism and the urinary tract, and the possible presence of rare genetic
      kidney stone diseases would require physicians to comprehensively evaluate
      patients presenting with kidney stones. The goal of evaluation is to identify
      modifiable risk factors and abnormalities for which targeted therapy can be
      prescribed. The goals of medical and surgical treatments are to eliminate the
      burden of kidney stones and prevent recurrence while simultaneously minimizing
      complications from interventions. Patients at high risk may benefit from a
      specialized kidney stone clinic staffed by a pediatric nephrologist, urologist,
      dietitian, and clinical nurse. Such a multidisciplinary clinic can help provide
      the medical and surgical support needed for patients at high risk and offer key
      opportunities to learn more about pediatric nephrolithiasis, thereby fueling the
      much-needed research in this field. 

PMID- 26302043
TI  - SB225002 Induces Cell Death and Cell Cycle Arrest in Acute Lymphoblastic Leukemia
      Cells through the Activation of GLIPR1.
AB  - Acute Lymphoblastic Leukemia (ALL) is the most frequent childhood malignancy. In
      the effort to find new anti-leukemic agents, we evaluated the small drug SB225002
      (N-(2-hydroxy-4-nitrophenyl)-N'-(2-bromophenyl)urea). Although initially
      described as a selective antagonist of CXCR2, later studies have identified other
      cellular targets for SB225002, with potential medicinal use in cancer. We found
      that SB225002 has a significant pro-apoptotic effect against both B- and T-ALL
      cell lines. Cell cycle analysis demonstrated that treatment with SB225002 induces
      G2-M cell cycle arrest. Transcriptional profiling revealed that SB225002-mediated
      apoptosis triggered a transcriptional program typical of tubulin binding agents.
      Network analysis revealed the activation of genes linked to the JUN and p53
      pathways and inhibition of genes linked to the TNF pathway. Early cellular
      effects activated by SB225002 included the up-regulation of GLIPR1, a p53-target
      gene shown to have pro-apoptotic activities in prostate and bladder cancer.
      Silencing of GLIPR1 in B- and T-ALL cell lines resulted in increased resistance
      to SB225002. Although SB225002 promoted ROS increase in ALL cells, antioxidant N
      Acetyl Cysteine pre-treatment only modestly attenuated cell death, implying that
      the pro-apoptotic effects of SB225002 are not exclusively mediated by ROS.
      Moreover, GLIPR1 silencing resulted in increased ROS levels both in untreated and
      SB225002-treated cells. In conclusion, SB225002 induces cell cycle arrest and
      apoptosis in different B- and T-ALL cell lines. Inhibition of tubulin function
      with concurrent activation of the p53 pathway, in particular, its downstream
      target GLIPR1, seems to underlie the anti-leukemic effect of SB225002. 

PMID- 26302044
TI  - Estimating the Impact of Earlier ART Initiation and Increased Testing Coverage on
      HIV Transmission among Men Who Have Sex with Men in Mexico using a Mathematical
      Model.
AB  - OBJECTIVE: To estimate the impact of late ART initiation on HIV transmission
      among men who have sex with men (MSM) in Mexico. METHODS: An HIV transmission
      model was built to estimate the number of infections transmitted by HIV-infected
      men who have sex with men (MSM-HIV+) MSM-HIV+ in the short and long term. Sexual
      risk behavior data were estimated from a nationwide study of MSM. CD4+ counts at
      ART initiation from a representative national cohort were used to estimate time
      since infection. Number of MSM-HIV+ on treatment and suppressed were estimated
      from surveillance and government reports. Status quo scenario (SQ), and scenarios
      of early ART initiation and increased HIV testing were modeled. RESULTS: We
      estimated 14239 new HIV infections per year from MSM-HIV+ in Mexico. In SQ, MSM
      take an average 7.4 years since infection to initiate treatment with a median
      CD4+ count of 148 cells/mm3(25th-75th percentiles 52-266). In SQ, 68% of MSM-HIV+
      are not aware of their HIV status and transmit 78% of new infections. Increasing
      the CD4+ count at ART initiation to 350 cells/mm3 shortened the time since
      infection to 2.8 years. Increasing HIV testing to cover 80% of undiagnosed MSM
      resulted in a reduction of 70% in new infections in 20 years. Initiating ART at
      500 cells/mm3 and increasing HIV testing the reduction would be of 75% in 20
      years. CONCLUSION: A substantial number of new HIV infections in Mexico are
      transmitted by undiagnosed and untreated MSM-HIV+. An aggressive increase in HIV
      testing coverage and initiating ART at a CD4 count of 500 cells/mm3 in this
      population would significantly benefit individuals and decrease the number of new
      HIV infections in Mexico.

PMID- 26302046
TI  - Identifying Patients with Colon Neoplasias with Gas Discharge Visualization
      Technique.
AB  - OBJECTIVE: To perform an initial assessment of the potential of using the gas
      discharge visualization (GDV) technique to identify patients with colon
      neoplasias. METHODS: The GDV camera (also known as the electrophotonic imaging
      camera) was used to assess the participants. Colonoscopy was performed on all 78
      participants, followed by a GDV scan. The control group consisted of 22 people.
      An endoscopic examination identified colon tumors in the remaining 56
      participants. Participant ages ranged from 45 to 86 years (mean, 64.6 +/- 1.2
      years). The study analyzed GDV images of each patient's fingers, presenting a
      whole-body view, as well as separate sectors corresponding to the organs in
      question. RESULTS: There was a significant number of differences between the
      control group and the patients with colon tumors. The dynamic of the parameters
      was examined as the level of tumor dysplasia (neoplasia) varied. The values of
      the following parameters decreased in the control group as compared to the
      patients with cancerous polyps: normalized luminescence area, internal noise,
      contour radius, and average luminescence intensity. The values of the following
      parameters increased in the control group: radius of the inscribed circle,
      contour line length, area of luminescence, contour line fractality, contour line
      entropy, and form coefficients. CONCLUSION: This pilot study demonstrated a
      statistical difference between the GDV parameters of patients with colon tumors
      and the control group. These findings warrant a more in-depth study of the
      potential for GDV technique in screening programs.

PMID- 26302047
TI  - Editorial.

PMID- 26302048
TI  - The Contrasting Character of Early and Late Transition Metal Fluorides as
      Hydrogen Bond Acceptors.
AB  - The association constants and enthalpies for the binding of hydrogen bond donors
      to group 10 transition metal complexes featuring a single fluoride ligand (trans
      [Ni(F)(2-C5NF4)(PR3)2], R = Et 1a, Cy 1b, trans-[Pd(F)(4-C5NF4)(PCy3)2] 2, trans
      [Pt(F){2-C5NF2H(CF3)}(PCy3)2] 3 and of group 4 difluorides (Cp2MF2, M = Ti 4a, Zr
      5a, Hf 6a; Cp*2MF2, M = Ti 4b, Zr 5b, Hf 6b) are reported. These measurements
      allow placement of these fluoride ligands on the scales of organic H-bond
      acceptor strength. The H-bond acceptor capability beta (Hunter scale) for the
      group 10 metal fluorides is far greater (1a 12.1, 1b 9.7, 2 11.6, 3 11.0) than
      that for group 4 metal fluorides (4a 5.8, 5a 4.7, 6a 4.7, 4b 6.9, 5b 5.6, 6b
      5.4), demonstrating that the group 10 fluorides are comparable to the strongest
      organic H-bond acceptors, such as Me3NO, whereas group 4 fluorides fall in the
      same range as N-bases aniline through pyridine. Additionally, the measurement of
      the binding enthalpy of 4-fluorophenol to 1a in carbon tetrachloride (-23.5 +/-
      0.3 kJ mol(-1)) interlocks our study with Laurence's scale of H-bond basicity of
      organic molecules. The much greater polarity of group 10 metal fluorides than
      that of the group 4 metal fluorides is consistent with the importance of ppi-dpi
      bonding in the latter. The polarity of the group 10 metal fluorides indicates
      their potential as building blocks for hydrogen-bonded assemblies. The synthesis
      of trans-[Ni(F){2-C5NF3(NH2)}(PEt3)2], which exhibits an extended chain structure
      assembled by hydrogen bonds between the amine and metal-fluoride groups, confirms
      this hypothesis. 

PMID- 26302049
TI  - Cell lineage tracing in human epithelial tissues using mitochondrial DNA
      mutations as clonal markers.
AB  - The study of cell lineages through heritable genetic lineage tracing is well
      established in experimental animals, particularly mice. While such techniques are
      not feasible in humans, we have taken advantage of the fact that the
      mitochondrial genome is highly prone to nonpathogenic mutations and such
      mutations can be used as clonal markers to identify stem cell derived clonal
      populations in human tissue sections. A mitochondrial DNA (mtDNA) mutation can
      spread by a stochastic process through the several copies of the circular genome
      in a single mitochondrion, and then through the many mitochondria in a single
      cell, a process called 'genetic drift.' This process takes many years and so is
      likely to occur only in stem cells, but once established, the fate of stem cell
      progeny can be followed. A cell having at least 80% of its mtDNA genomes bearing
      the mutation results in a demonstrable deficiency in mtDNA-encoded cytochrome c
      oxidase (CCO), optimally detected in frozen tissue sections by dual-color
      histochemistry, whereby CCO activity stains brown and CCO deficiency is
      highlighted by subsequent succinate dehydrogenase activity, staining the CCO
      deficient areas blue. Cells with CCO deficiency can be laser captured and
      subsequent mtDNA sequencing can ascertain the nature of the mutation. If all
      cells in a CCO-deficient area have an identical mutation, then a clonal
      population has been identified; the chances of the same mutation initially
      arising in separate cells are highly improbable. The technique lends itself to
      the study of both normal epithelia and can answer several questions in tumor
      biology. WIREs Dev Biol 2016, 5:103-117. doi: 10.1002/wdev.203 For further
      resources related to this article, please visit the WIREs website. 

PMID- 26302051
TI  - Explaining the link between objective and perceived differences in groups: The
      role of the belonging and distinctiveness motives.
AB  - Group diversity research often focuses on objective diversity, or the actual
      compositional attributes of the group (e.g., differences in sex or functional
      background), and its impact on group processes and performance. More recently,
      diversity researchers have called for consideration of group members' perceptions
      of diversity, or their subjective understanding of differences within their
      group, because these perceptions have important effects on group outcomes. In
      fact, research has indicated only a modest correlation between objective and
      perceived diversity. Although the subjective nature of group diversity has
      important implications for group outcomes, we are still unclear about why and
      when perceived diversity diverges from objective diversity. In this article, I
      examine the role of identity motives, or motives that guide self-definition, in
      shaping member's perceptions of themselves and their group's composition. I argue
      that group members want to balance their needs for belonging and distinctiveness,
      but high levels of objective differences make them feel too distinct whereas low
      levels of objective differences makes them feel too deindividuated. Individual
      differences in the need to belong and be distinct further influence the degree to
      which these motives are satisfied. In turn, when these motives are unsatisfied,
      they will affect members' perceptions of differences. The presented theory helps
      to explain the discrepancy between objective differences and members' perceptions
      of differences, and ultimately helps integrate opposing findings in the diversity
      literature.

PMID- 26302050
TI  - HLA Class-II Associated HIV Polymorphisms Predict Escape from CD4+ T Cell
      Responses.
AB  - Antiretroviral therapy, antibody and CD8+ T cell-mediated responses targeting
      human immunodeficiency virus-1 (HIV-1) exert selection pressure on the virus
      necessitating escape; however, the ability of CD4+ T cells to exert selective
      pressure remains unclear. Using a computational approach on HIV gag/pol/nef
      sequences and HLA-II allelic data, we identified 29 HLA-II associated HIV
      sequence polymorphisms or adaptations (HLA-AP) in an African cohort of
      chronically HIV-infected individuals. Epitopes encompassing the predicted
      adaptation (AE) or its non-adapted (NAE) version were evaluated for
      immunogenicity. Using a CD8-depleted IFN-gamma ELISpot assay, we determined that
      the magnitude of CD4+ T cell responses to the predicted epitopes in controllers
      was higher compared to non-controllers (p<0.0001). However, regardless of the
      group, the magnitude of responses to AE was lower as compared to NAE (p<0.0001).
      CD4+ T cell responses in patients with acute HIV infection (AHI) demonstrated
      poor immunogenicity towards AE as compared to NAE encoded by their transmitted
      founder virus. Longitudinal data in AHI off antiretroviral therapy demonstrated
      sequence changes that were biologically confirmed to represent CD4+ escape
      mutations. These data demonstrate an innovative application of HLA-associated
      polymorphisms to identify biologically relevant CD4+ epitopes and suggests CD4+ T
      cells are active participants in driving HIV evolution. 

PMID- 26302052
TI  - An integrative account of constraints on cross-situational learning.
AB  - Word-object co-occurrence statistics are a powerful information source for
      vocabulary learning, but there is considerable debate about how learners actually
      use them. While some theories hold that learners accumulate graded, statistical
      evidence about multiple referents for each word, others suggest that they track
      only a single candidate referent. In two large-scale experiments, we show that
      neither account is sufficient: Cross-situational learning involves elements of
      both. Further, the empirical data are captured by a computational model that
      formalizes how memory and attention interact with co-occurrence tracking.
      Together, the data and model unify opposing positions in a complex debate and
      underscore the value of understanding the interaction between computational and
      algorithmic levels of explanation. 

PMID- 26302053
TI  - Divided and disconnected--an examination of youths' experiences with emotional
      distress within the context of their everyday lives.
AB  - This paper is based on a qualitative study conducted in a rural community in
      British Columbia, Canada. Ethnographic methods were used to: (1) to bring youth
      voice to the literature on emotional distress; and (2) to capture the ways in
      which context shapes young peoples' experiences of emotional distress within
      their everyday lives. Our findings demonstrate how socio-structural contextual
      factors such as the local economy, geographical segregation, racism, ageism, and
      cutbacks in health and social service programming operate to create various forms
      of disconnection, and intersect in young peoples' lives to shape their
      experiences of emotional distress. 

PMID- 26302054
TI  - Chiral Insecticide alpha-Cypermethrin and Its Metabolites: Stereoselective
      Degradation Behavior in Soils and the Toxicity to Earthworm Eisenia fetida.
AB  - The enantioselective degradation of the widely used chiral insecticide alpha
      cypermethrin in soils has been investigated, and its main metabolites cis-3
      (2',2'-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis-DCCA) and 3
      phenoxybenzoic acid (3-PBA), which have potential environmental problems, have
      also been determined. The enantiomers of alpha-cypermethrin were separated on
      Chiralcel OD chiral columns by high-performance liquid chromatography (HPLC)
      under normal phase, and the metabolites were detected by gas chromatography (GC)
      after derivatization. The results of the degradation showed that alpha
      cypermethrin dissipated in soils with relatively long half-lives of 12.70-47.08
      days and obvious stereoselective degradation of the two enantiomers was observed
      in the five soils, with enantiomeric fraction (EF) from 0.55 to 0.61 after 42
      days, indicating that (+)-(1R,cis,alphaS) enantiomer was preferentially degraded.
      cis-DCCA and 3-PBA were formed in all of the soils, and it was found that the
      amount generated was related to the soil pH. cis-DCCA was easily generated in the
      acidic soils, while more 3-PBA tended to be generated in the soil of pH over 7.
      To evaluate the impact on soil animals, the toxicity, including the combined
      toxicity of cis-DCCA, 3-PBA, and alpha-cypermethrin, to earthworm (Eisenia
      fetida) was studied. The results of enantioselective transformation of alpha
      cypermethrin in soils and the toxicity of alpha-cypermethrin and its metabolites
      to earthworm have some implications for environmental risk and food safety
      evaluations. 

PMID- 26302055
TI  - Contact dermatitis to topical acne drugs: a review of the literature.
AB  - Acne vulgaris is a chronic dermatological disorder that affects the majority of
      teenagers in the Western world. Topical therapy is widely used to treat mild
      moderate acne and is known as well-tolerated thanks to its low systemic toxicity,
      although associated to skin adverse effects. Acne seems to be associated also to
      an intrinsic alteration of the epidermal barrier, regarding both the upper and
      the follicular stratum corneum that promotes the onset of such local side
      effects. The commonest one is irritant contact dermatitis, an event of frequent
      observation occurring with erythema, burning, dryness, scaling, and itching,
      usually characterized by low severity and limited duration. Among topical acne
      drugs, retinoids are the most irritating ones. Another side effect is allergic
      contact dermatitis: it is rare and mainly associated to benzoyl peroxide. 

PMID- 26302056
TI  - Transition Metal-Free Oxidative Radical Decarboxylation/Cyclization for the
      Construction of 6-Alkyl/Aryl Phenanthridines.
AB  - A radical cascade decarboxylation/cyclization of 2-isocyanobiphenyls with
      aliphatic carboxylic acids as well as aromatic carboxylic acids under the
      transition metal-free conditions was reported. This process, which included
      formation of two new C-C bonds and cleavage of C-COOH bonds, afforded a novel and
      environmentally friendly approach to producing 6-alkyl/aryl phenanthridines with
      moderate to good yields. 

PMID- 26302058
TI  - Electrochemical flow injection analysis of hydrazine in an excess of an active
      pharmaceutical ingredient: achieving pharmaceutical detection limits
      electrochemically.
AB  - The quantification of genotoxic impurities (GIs) such as hydrazine (HZ) is of
      critical importance in the pharmaceutical industry in order to uphold drug
      safety. HZ is a particularly intractable GI and its detection represents a
      significant technical challenge. Here, we present, for the first time, the use of
      electrochemical analysis to achieve the required detection limits by the
      pharmaceutical industry for the detection of HZ in the presence of a large excess
      of a common active pharmaceutical ingredient (API), acetaminophen (ACM) which
      itself is redox active, typical of many APIs. A flow injection analysis approach
      with electrochemical detection (FIA-EC) is utilized, in conjunction with a
      coplanar boron doped diamond (BDD) microband electrode, insulated in an
      insulating diamond platform for durability and integrated into a two piece flow
      cell. In order to separate the electrochemical signature for HZ such that it is
      not obscured by that of the ACM (present in excess), the BDD electrode is
      functionalized with Pt nanoparticles (NPs) to significantly shift the half wave
      potential for HZ oxidation to less positive potentials. Microstereolithography
      was used to fabricate flow cells with defined hydrodynamics which minimize
      dispersion of the analyte and optimize detection sensitivity. Importantly, the Pt
      NPs were shown to be stable under flow, and a limit of detection of 64.5 nM or
      0.274 ppm for HZ with respect to the ACM, present in excess, was achieved. This
      represents the first electrochemical approach which surpasses the required
      detection limits set by the pharmaceutical industry for HZ detection in the
      presence of an API and paves the wave for online analysis and application to
      other GI and API systems. 

PMID- 26302057
TI  - Protection against Paracoccidioides brasiliensis infection in mice treated with
      modulated dendritic cells relies on inhibition of interleukin-10 production by
      CD8+ T cells.
AB  - Paracoccidioidomycosis is a systemic infection prevalent in Latin American
      countries. Disease develops after inhalation of Paracoccidioides brasiliensis
      conidia followed by an improper immune activation by the host leucocytes.
      Dendritic cells (DCs) are antigen-presenting cells with the unique ability to
      direct the adaptive immune response by the time of activation of naive T cells.
      This study was conducted to test whether extracts of P. brasiliensis would induce
      maturation of DCs. We found that DCs treated with extracts acquired an
      inflammatory phenotype and upon adoptive transfer conferred protection to
      infection. Interestingly, interleukin-10 production by CD8(+) T cells was ablated
      following DC transfer. Further analyses showed that lymphocytes from infected
      mice were high producers of interleukin-10, with CD8(+) T cells being the main
      source. Blockage of cross-presentation to CD8(+) T cells by modulated DCs
      abolished the protective effect of adoptive transfer. Collectively, our data show
      that adoptive transfer of P. brasiliensis-modulated DCs is an interesting
      approach for the control of infection in paracoccidioidomycosis. 

PMID- 26302059
TI  - Ramipril and haloperidol as promising approaches in managing rheumatoid arthritis
      in rats.
AB  - Rheumatoid arthritis (RA) is a challenging autoimmune disorder, whose treatments
      usually cause severe gastrointestinal, renal and other complications. We aimed to
      evaluate the beneficial anti-arthritic effects of an angiotensin converting
      enzyme (ACE) inhibitor, ramipril and a dopamine receptor blocker, haloperidol, on
      Complete Freund's Adjuvant-induced RA in adult female albino rats. Rats were
      allocated into a normal control group, an arthritis control group, two reference
      treatment groups receiving dexamethasone (1.5 mg/kg/day) and methotrexate (1
      mg/kg/day), and two treatment groups receiving ramipril (0.9 mg/kg/day) and
      haloperidol (1 mg/kg/day). Serum rheumatoid factor, matrix metalloprotinease-3
      (MMP-3) and cartilage oligomeric matrix protein as specific rheumatoid
      biomarkers, serum immunoglobulin G and antinuclear antibody as immunological
      biomarkers, serum tumor necrosis factor alpha (TNF-alpha) and interleukin-10 (IL
      10) as immunomodulatory cytokines, serum myeloperoxidase and C-reactive protein
      as inflammatory biomarkers, as well as malondialdehyde and glutathione reduced
      (GSH) as oxidative stress biomarkers were assessed. A histopathological study on
      joints and spleens was performed to support the results of biochemical
      estimations. Ramipril administration significantly corrected all the measured
      biomarkers, being restored back to normal levels except for MMP-3, TNF-alpha and
      IL-10. Haloperidol administration restored all the measured biomarkers back to
      normal levels except for TNF-alpha, IL-10 and GSH. In conclusion, ACE inhibitors
      represented by ramipril and dopamine receptor blockers represented by haloperidol
      may represent new promising protective strategies against RA, at least owing to
      their immunomodulatory, anti-inflammatory and antioxidant potentials.

PMID- 26302060
TI  - Neuroprotective effects of an oxyntomodulin analogue in the MPTP mouse model of
      Parkinson's disease.
AB  - Oxyntomodulin is a hormone and a growth factor. It activates two receptors, the
      Glucagon-like peptide 1 (GLP-1) and the glucagon receptor. GLP-1 mimetics are on
      the market as treatments for type 2 diabetes and are well tolerated. These drugs
      have shown neuroprotective properties in animal models of neurodegenerative
      disorders. In addition, the GLP-1 mimetic exendin-4 has shown protective effects
      in animal models of Parkinson's disease (PD), and a clinical trial in PD patients
      showed promising first positive results. D-Ser2-oxyntomodulin (Oxy) is a protease
      resistant oxyntomodulin analogue that has been developed to treat diabetes. Here
      we demonstrate for the first time that such analogues have neuroprotective
      effects. The drug showed protective effects in the 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) mouse model of PD. MPTP was injected daily (20 mg/kg
      i.p.) for 7 days, and Oxy injected once-daily for 14 days i.p. Oxy treatment
      prevented or reversed the MPTP- induced motor impairment (Rotarod, spontaneous
      locomotion, swim activity, muscle strength test), the MPTP-induced reduction in
      Tyrosine Hydroxylase (TH) levels (dopamine synthesis) in the substantia nigra and
      basal ganglia, the reduction of the synaptic marker synapstophysin, the
      inactivation of the growth factor kinase Akt/PKB and of the anti-apoptotic
      signaling molecule Bcl-2, and the increase of levels of the pro-inflammatory
      cytokine TNF-alpha. The results demonstrate that oxyntomodulin analogues show
      promise as a novel treatment of PD.

PMID- 26302061
TI  - Eosinophilic Esophagitis in Children with Esophageal Atresia.
AB  - Recent studies have reported a higher prevalence of eosinophilic esophagitis in
      children with esophageal atresia. Under recognition of eosinophilic esophagitis
      in these patients may lead to excessive use of antireflux therapy and an
      escalation of interventions, including fundoplication, as symptoms may be
      attributed to gastroesophageal reflux disease. In addition, long-term untreated
      eosinophilic esophagitis may lead to recurrent strictures due to transmural
      esophageal inflammation, necessitating repeated dilatations. Eosinophilic
      esophagitis should be considered when children with esophageal atresia show
      persistent symptoms on standard antireflux treatment, increasing dysphagia, and
      recurrent strictures. Treatment has been found to not only significantly reduce
      intraepithelial eosinophil count, but also to improve symptoms, and to lower the
      occurrence of strictures and the need for dilatations. Future prospective studies
      are warranted in this area. 

PMID- 26302062
TI  - Screening and Surveillance in Esophageal Atresia Patients: Current Knowledge and
      Future Perspectives.
AB  - Esophageal atresia (EA) is a rare congenital anomaly. Enhanced operative
      techniques and intensive care treatment have improved survival among children
      with repaired EA (range, 93-95%). Many (up to 67%) suffer from gastroesophageal
      reflux (GER). The high incidence of GER and improved survival among EA patients
      raises concerns about an increased risk of developing Barrett esophagus (BE) and
      esophageal cancer. This review provides an overview of the prevalence of
      esophagitis, BE, and esophageal cancer in EA patients and outlines suggestions
      for future research. A literature search indeed revealed a higher prevalence of
      BE in EA patients than in the generalized population and that this condition
      occurs at a much younger age. It should be noted that in some studies gastric
      metaplasia without intestinal metaplasia is defined as BE. Gastric-type mucosa in
      columnar-lined esophagus is probably of less clinical importance in terms of the
      likelihood of malignant transformation. Its inclusion therefore confounds the
      risk of esophageal adenocarcinoma. A total of eight cases of esophageal carcinoma
      at a young age, either squamous cell carcinoma or adenocarcinoma, have been
      reported. These observations bear important implications prompting for early
      onset lifelong BE/esophageal cancer surveillance to facilitate the diagnosis of
      (pre)neoplastic changes and early treatment. 

PMID- 26302063
TI  - Bridging the Gap in the Repair of Long-Gap Esophageal Atresia: Still Questions on
      Diagnostics and Treatment.
AB  - Long-gap esophageal atresia remains a complex surgical problem fraught with
      complications and poor outcomes in many patients. This review covers the
      techniques and strategies currently used to address this congenital anomaly. The
      techniques covered include preservation of the native esophagus, esophageal
      elongation techniques, esophageal replacement, and evolving work on tissue
      engineering. 

PMID- 26302064
TI  - Obesity and carotid artery remodeling.
AB  - BACKGROUND/OBJECTIVE: The present study tested the hypothesis that obesity
      related changes in carotid intima-media thickness (IMT) might represent not only
      preclinical atherosclerosis but an adaptive remodeling meant to preserve
      circumferential wall stress (CWS) in altered hemodynamic conditions characterized
      by body size-dependent increase in stroke volume (SV) and blood pressure (BP).
      SUBJECTS/METHODS: Common carotid artery (CCA) luminal diameter (LD), IMT and CWS
      were measured in three different populations in order to study: (A) cross
      sectional associations between SV, BP, anthropometric parameters and CCA LD (266
      healthy subjects with wide range of body weight (24-159 kg)); (B) longitudinal
      associations between CCA LD and 3-year IMT progression rate (DeltaIMT; 571
      healthy non-obese subjects without increased cardiovascular (CV) risk); (C) the
      impact of obesity on CCA geometry and CWS (88 obese subjects without CV
      complications and 88 non-obese subjects matched for gender and age). RESULTS: CCA
      LD was independently associated with SV that was determined by body size. In the
      longitudinal study, baseline LD was an independent determinant of DeltaIMT, and
      DeltaIMT of subjects in the highest LD quartile was significantly higher (28+/-3
      MUm) as compared with those in the lower quartiles (8+/-3, 16+/-4 and 16+/-3 MUm,
      P=0.001, P<0.05 and P=0.01, respectively). In addition, CCA CWS decreased during
      the observational period in the highest LD quartile (from 54.2+/-8.6 to 51.6+/
      7.4 kPa, P<0.0001). As compared with gender- and age-matched lean individuals,
      obese subjects had highly increased CCA LD and BP (P<0.0001 for both), but only
      slightly higher CWS (P=0.05) due to a significant increase in IMT (P=0.005 after
      adjustment for confounders). CONCLUSIONS: Our findings suggest that in obese
      subjects, the CCA wall thickens to compensate the luminal enlargement caused by
      body size-induced increase in SV, and therefore, to normalize the wall stress.
      CCA diameter in obesity could represent an additional biomarker, depicting the
      impact of altered hemodynamics on arterial wall.

PMID- 26302065
TI  - Differential expression of hypothalamic, metabolic and inflammatory genes in
      response to short-term calorie restriction in juvenile obese- and lean-prone JCR
      rats.
AB  - BACKGROUND: Childhood obesity is an important early predictor of adult obesity
      and associated comorbidities. Common forms of obesity are underpinned by both
      environmental and genetic factors. However, the rising prevalence of obesity in
      genetically stable populations strongly suggests that contemporary lifestyle is a
      premier factor to the disease. In pediatric population, the current
      treatment/prevention options for obesity are lifestyle interventions such as
      caloric restriction (CR) and increase physical activity. In obese individuals, CR
      improves many metabolic parameters in peripheral tissues. Little is known about
      the effect of CR on the hypothalamus. This study aimed to assess the effect of CR
      on hypothalamic metabolic gene expression of young obese- and lean-prone animals.
      METHODS: Male juvenile JCR:LA-cp obese-prone rats were freely fed (Obese-FF) or
      pair fed (Obese-FR) to lean-prone, free-feeding animals (Lean-FF). A group of
      lean-prone rats (Lean-FR) were matched for relative average degree of CR to Obese
      FR rats. RESULTS: In free-feeding conditions, obese-prone rats consumed more
      energy than lean-prone rats (P<0.001) and showed greater increases in body
      weight, fat mass, plasma glucose, insulin and lipids (P<0.01). These metabolic
      differences were associated with alterations of feeding-related neuropeptides
      expression in the hypothalamus, as well as pro-inflammatory cytokines and
      oxidative stress markers. When submitted to the same degree of CR, the two
      genotypes responded differently; hypothalamic inflammatory and oxidative stress
      gene expression was improved in Obese-FR, while it was worsened in Lean-FR rats.
      CONCLUSIONS: We demonstrate in JCR rats that the metabolic and inflammatory
      response of the brain to CR is genotype dependent.

PMID- 26302066
TI  - Effects of low-fat diet and aging on metabolic profiles of Creb3l4 knockout mice.
AB  - BACKGROUND/OBJECTIVES: Increased adipose tissue mass closely associates with the
      development of insulin resistance and type 2 diabetes mellitus. Previously, we
      reported that CREB3L4 expressed in adipose tissue negatively regulates
      adipogenesis, and Creb3l4 knockout mice fed a high-fat diet for 16 weeks showed
      fat cell hyperplasia, with improved glucose tolerance and insulin sensitivity.
      These mice did not show significant weight gain and fat mass. Because fat diet or
      aging is known to be associated with the development of obesity, we examined the
      effects of Creb3l4 gene subjected to low-fat diet (LFD) or aging process on body
      composition and obesity risk. SUBJECTS/METHODS: We fed Creb3l4 knockout mice a
      low-fat diet for 16 weeks (LFD group) or chow diet for over 1 year (aged group)
      and observed various metabolic parameters in the LFD-fed and aged Creb3l4
      knockout mice. RESULTS: LFD-fed and aged Creb3l4 knockout mice showed significant
      weight gain and adiposity, impaired glucose tolerance and decreased insulin
      sensitivity, compared with wild-type mice. CONCLUSIONS: Creb3l4 has a critical
      role in metabolic phenotypes and a better understanding of its function may
      provide improved insight into the etiology of diabetes and other metabolic
      disorders.

PMID- 26302067
TI  - Control of bacterial adhesion and growth on honeycomb-like patterned surfaces.
AB  - It is a great challenge to construct a persistent bacteria-resistant surface even
      though it has been demonstrated that several surface features might be used to
      control bacterial behavior, including surface topography. In this study, we
      develop micro-scale honeycomb-like patterns of different sizes (0.5-10 MUm) as
      well as a flat area as the control on a single platform to evaluate the bacterial
      adhesion and growth. Bacteria strains, Escherichia coli and Staphylococcus aureus
      with two distinct shapes (rod and sphere) are cultured on the platforms, with the
      patterned surface-up and surface-down in the culture medium. The results
      demonstrate that the 1 MUm patterns remarkably reduce bacterial adhesion and
      growth while suppressing bacterial colonization when compared to the flat
      surface. The selective adhesion of the bacterial cells on the patterns reveals
      that the bacterial adhesion is cooperatively mediated by maximizing the cell
      substrate contact area and minimizing the cell deformation, from a thermodynamic
      point of view. Moreover, study of bacterial behaviors on the surface-up vs.
      surface-down samples shows that gravity does not apparently affect the spatial
      distribution of the adherent cells although it indeed facilitates bacterial
      adhesion. Furthermore, the experimental results suggest that two major factors,
      i.e. the availability of energetically favorable adhesion sites and the physical
      confinements, contribute to the anti-bacterial nature of the honeycomb-like
      patterns.

PMID- 26302068
TI  - BRAF Inhibition Generates a Host-Tumor Niche that Mediates Therapeutic Escape.
AB  - The current study defines a fibroblast-derived niche that facilitates the
      therapeutic escape of melanoma cells from BRAF inhibition. Vemurafenib treatment
      led to the release of transforming growth factor-beta (TGF-beta) from the
      melanoma cells that increased the differentiation state of the fibroblasts, an
      affect associated with fibronectin deposition, increase in alpha-smooth muscle
      actin expression, and the release of neuregulin (NRG). At the same time,
      vemurafenib directly activated the fibroblasts through paradoxical stimulation of
      the mitogen-activated protein kinase pathway, causing them to secrete hepatocyte
      growth factor (HGF). Treatment with the BRAF/MEK inhibitor combination reversed
      the release of HGF. Adhesion of melanoma cells to fibronectin was critical in
      amplifying the fibroblast-derived NRG- and HGF-mediated PI3K/AKT
      (phosphatidylinositol 3'-kinase/AKT) survival signaling in the melanoma cells
      following BRAF inhibition. In coculture studies, combination treatment with
      inhibitors of BRAF/MET/HER kinase was ineffective at reversing the fibroblast
      mediated therapeutic escape from BRAF inhibition. Instead, it was noted that
      combined BRAF/PI3K inhibition overcame fibroblast-mediated drug resistance in
      vitro and was associated with enhanced antitumor effects in an in vivo xenograft
      model. Thus, we show that melanoma cells and fibroblasts remodel their
      microenvironment in response to BRAF inhibition and that these adaptations allow
      tumor cells to evade therapy through increased PI3K/AKT survival signaling. 

PMID- 26302073
TI  - Visual imagery.
AB  - Visual mental imagery is our ability to reactivate and manipulate visual
      representations in the absence of the corresponding visual stimuli, giving rise
      to the experience of 'seeing with the mind's eye'. Until relatively recently,
      visual mental imagery had been investigated by philosophy and cognitive
      psychology. However, these disciplines did not have the tools required to address
      empirically some of the important questions they had raised, for instance the
      extent to which visual mental images rely on some of the same representations
      that support visual perception. During the last two decades, cognitive
      neuroscience has leveraged the vast amount of knowledge about the neural basis of
      primate vision to provide new insights into visual mental imagery processes. Such
      insights enabled the empirical test of key questions about visual mental imagery
      using the armamentarium of tools provided by cognitive neuroscience, including
      electrophysiology and neuroimaging. Using a similar logic, we propose that
      information about the neural basis of memory systems should be used to further
      enhance understanding of the neural mechanisms of visual mental imagery. WIREs
      Cogni Sci 2011 2 239-252 DOI: 10.1002/wcs.103 For further resources related to
      this article, please visit the WIREs website. 

PMID- 26302070
TI  - Healthcare Services Utilization and Drug Use in Patients with Chronic Urticaria.

PMID- 26302069
TI  - Notch1 Pathway Activation Results from the Epigenetic Abrogation of Notch-Related
      MicroRNAs in Mycosis Fungoides.
AB  - Notch is a family of transmembrane receptors that participate in the regulation
      of cell differentiation, proliferation, and stemness. Notch pathway activation
      has also been found associated with different human cancers including primary
      cutaneous T-cell lymphomas (CTCL). The elucidation of the mechanisms driving
      Notch activation in these particular diseases has remained elusive. Here we
      studied the possibility that DNA methylation at Notch pathway gene promoters
      and/or deregulation of Notch-associated microRNAs contribute to activate Notch in
      mycosis fungoides (MF). By genome-wide DNA methylation analysis, we failed to
      detect any consistent methylation at the Notch1, the Notch-ligand Jagged1, or the
      Notch-target Hes1 gene promoters, but found a significant methylation of the
      Notch-related microRNAs, in particular miR-200c and miR-124. Downregulation of
      miR-200c is associated with overexpression of Jagged1, concomitant to Notch1
      activation. CTCL cell lines were infected with lentiviral vector encoding for miR
      200c and ectopic expression of miR-200c in CTCL lines resulted in Jagged1 protein
      downregulation associated with a reduction in the levels of active Notch1. Our
      study deciphers an epigenetic mechanism regulating the Notch pathway in (MF) that
      might contribute to the future design of more specific therapeutic strategies. 

PMID- 26302074
TI  - Linguistic relativity.
AB  - The central question in research on linguistic relativity, or the Whorfian
      hypothesis, is whether people who speak different languages think differently.
      The recent resurgence of research on this question can be attributed, in part, to
      new insights about the ways in which language might impact thought. We identify
      seven categories of hypotheses about the possible effects of language on thought
      across a wide range of domains, including motion, color, spatial relations,
      number, and false belief understanding. While we do not find support for the idea
      that language determines the basic categories of thought or that it overwrites
      preexisting conceptual distinctions, we do find support for the proposal that
      language can make some distinctions difficult to avoid, as well as for the
      proposal that language can augment certain types of thinking. Further, we
      highlight recent evidence suggesting that language may induce a relatively
      schematic mode of thinking. Although the literature on linguistic relativity
      remains contentious, there is growing support for the view that language has a
      profound effect on thought. WIREs Cogni Sci 2011 2 253-265 DOI: 10.1002/wcs.104
      For further resources related to this article, please visit the WIREs website. 

PMID- 26302075
TI  - Computational models of analogy.
AB  - Analogical mapping is a core process in human cognition. A number of valuable
      computational models of analogy have been created, capturing aspects of how
      people compare representations, retrieve potential analogs from memory, and learn
      from the results. In the past 25 years, this area has progressed rapidly, fueled
      by strong collaboration between psychologists and Artificial Intelligence (AI)
      scientists, with contributions from linguists and philosophers as well. There is
      now considerable consensus regarding the constraints governing the mapping
      process. However, computational models still differ in their focus, with some
      aimed at capturing the range of analogical phenomena at the cognitive level and
      others aimed at modeling how analogical processes might be implemented in neural
      systems. Some recent work has focused on modeling interactions between analogy
      and other processes, and on modeling analogy as a part of larger cognitive
      systems. WIREs Cogni Sci 2011 2 266-276 DOI: 10.1002/wcs.105 For further
      resources related to this article, please visit the WIREs website. 

PMID- 26302076
TI  - Second language acquisition.
AB  - Second language acquisition (SLA) is a field that investigates child and adult
      SLA from a variety of theoretical perspectives. This article provides a survey of
      some key areas of concern including formal generative theory and emergentist
      theory in the areas of morpho-syntax and phonology. The review details the
      theoretical stance of the two different approaches to the nature of language:
      generative linguistics and general cognitive approaches. Some results of key
      acquisition studies from the two theoretical frameworks are discussed. From a
      generative perspective, constraints on wh-movement, feature geometry and syllable
      structure, and morphological development are highlighted. From a general
      cognitive point of view, the emergence of tense and aspect marking from a
      prototype account of inherent lexical aspect is reviewed. Reference is made to
      general cognitive learning theories and to sociocultural theory. The article also
      reviews individual differences research, specifically debate on the critical
      period in adult language acquisition, motivation, and memory. Finally, the
      article discusses the relationship between SLA research and second language
      pedagogy. Suggestions for further reading from recent handbooks on SLA are
      provided. WIREs Cogni Sci 2011 2 277-286 DOI: 10.1002/wcs.106 For further
      resources related to this article, please visit the WIREs website. 

PMID- 26302077
TI  - Space and time in the context of equilibrium-point theory.
AB  - Advances to the equilibrium-point (EP) theory and solutions to several classical
      problems of action and perception are suggested and discussed. Among them are (1)
      the posture-movement problem of how movements away from a stable posture can be
      made without evoking resistance of posture-stabilizing mechanisms resulting from
      intrinsic muscle and reflex properties; (2) the problem of kinesthesia or why our
      sense of limb position is fairly accurate despite ambiguous positional
      information delivered by proprioceptive and cutaneous signals; (3) the redundancy
      problems in the control of multiple muscles and degrees of freedom. Central to
      the EP hypothesis is the notion that there are specific neural structures that
      represent spatial frames of reference (FRs) selected by the brain in a task
      specific way from a set of available FRs. The brain is also able to translate
      or/and rotate the selected FRs by modifying their major attributes-the origin,
      metrics, and orientation-and thus substantially influence, in a feed-forward
      manner, action and perception. The brain does not directly solve redundancy
      problems: it only limits the amount of redundancy by predetermining where, in
      spatial coordinates, a task-specific action should emerge and allows all motor
      elements, including the environment, to interact to deliver a unique action, thus
      solving the redundancy problem (natural selection of action). The EP theory
      predicts the existence of specific neurons associated with the control of
      different attributes of FRs and explains the role of mirror neurons in the
      inferior frontal gyrus and place cells in the hippocampus. WIREs Cogni Sci 2011 2
      287-304 DOI: 10.1002/wcs.108 For further resources related to this article,
      please visit the WIREs website. 

PMID- 26302078
TI  - Motion perception: behavior and neural substrate.
AB  - Visual motion perception is vital for survival. Single-unit recordings in primate
      primary visual cortex (V1) have revealed the existence of specialized motion
      sensing neurons; perceptual effects such as the motion after-effect demonstrate
      their importance for motion perception. Human psychophysical data on motion
      detection can be explained by a computational model of cortical motion sensors.
      Both psychophysical and physiological data reveal at least two classes of motion
      sensor capable of sensing motion in luminance-defined and texture-defined
      patterns, respectively. Psychophysical experiments also reveal that motion can be
      seen independently of motion sensor output, based on attentive tracking of visual
      features. Sensor outputs are inherently ambiguous, due to the problem of
      univariance in neural responses. In order to compute stimulus direction and
      speed, the visual system must compare the responses of many different sensors
      sensitive to different directions and speeds. Physiological data show that this
      computation occurs in the visual middle temporal (MT) area. Recent psychophysical
      studies indicate that information about spatial form may also play a role in
      motion computations. Adaptation studies show that the human visual system is
      selectively sensitive to large-scale optic flow patterns, and physiological
      studies indicate that cells in the middle superior temporal (MST) area derive
      this sensitivity from the combined responses of many MT cells. Extraretinal
      signals used to control eye movements are an important source of signals to
      cancel out the retinal motion responses generated by eye movements, though visual
      information also plays a role. A number of issues remain to be resolved at all
      levels of the motion-processing hierarchy. WIREs Cogni Sci 2011 2 305-314 DOI:
      10.1002/wcs.110 For further resources related to this article, please visit the
      WIREs website Additional Supporting Information may be found in
      http://www.lifesci.sussex.ac.uk/home/George_Mather/Motion/index.html. 

PMID- 26302079
TI  - Statistical methods in language processing.
AB  - The term statistical methods here refers to a methodology that has been dominant
      in computational linguistics since about 1990. It is characterized by the use of
      stochastic models, substantial data sets, machine learning, and rigorous
      experimental evaluation. The shift to statistical methods in computational
      linguistics parallels a movement in artificial intelligence more broadly.
      Statistical methods have so thoroughly permeated computational linguistics that
      almost all work in the field draws on them in some way. There has, however, been
      little penetration of the methods into general linguistics. The methods
      themselves are largely borrowed from machine learning and information theory. We
      limit attention to that which has direct applicability to language processing,
      though the methods are quite general and have many nonlinguistic applications.
      Not every use of statistics in language processing falls under statistical
      methods as we use the term. Standard hypothesis testing and experimental design,
      for example, are not covered in this article. WIREs Cogni Sci 2011 2 315-322 DOI:
      10.1002/wcs.111 For further resources related to this article, please visit the
      WIREs website. 

PMID- 26302080
TI  - On language 'utility': processing complexity and communicative efficiency.
AB  - Functionalist typologists have long argued that pressures associated with
      language usage influence the distribution of grammatical properties across the
      world's languages. Specifically, grammatical properties may be observed more
      often across languages because they improve a language's utility or decrease its
      complexity. While this approach to the study of typology offers the potential of
      explaining grammatical patterns in terms of general principles rather than domain
      specific constraints, the notions of utility and complexity are more often
      grounded in intuition than empirical findings. A suitable empirical foundation
      might be found in the terms of processing preferences: in that case,
      psycholinguistic measures of complexity are then expected correlate with
      typological patterns. We summarize half a century of psycholinguistic work on
      'processing complexity' in an attempt to make this work accessible to a broader
      audience: What makes something hard to process for comprehenders, and what
      determines speakers' preferences in production? We also briefly discuss recently
      emerging approaches that link preferences in production to communicative
      efficiency. These approaches can be seen as providing well-defined measures of
      utility. With these psycholinguistic findings in mind, it is possible to
      investigate the extent to which language usage is reflected in typological
      patterns. We close with a summary of paradigms that allow the link between
      language usage and typology to be studied empirically. WIREs Cogni Sci 2011 2 323
      335 DOI: 10.1002/wcs.126 For further resources related to this article, please
      visit the WIREs website. 

PMID- 26302081
TI  - Attentional blink and repetition blindness.
AB  - When two masked, to-be-attended targets are presented within half a second of
      each other, report accuracy for the second target (T2) is impaired relative to
      when the two targets are presented farther apart in time or relative to when the
      first target (T1) can be ignored. This effect is known as the attentional blink
      (AB). An additional T2 accuracy deficit is observed if T1 and T2 are identical or
      highly similar on a task-relevant dimension. This effect is known as repetition
      blindness (RB). For both AB and RB, targets are typically imbedded in rapid
      serial visual presentation (RSVP) streams and the dual-task attention cost lasts
      approximately half a second. Given the high degree of superficial similarity, AB
      and RB are often considered to be related phenomena. Although research thus far
      has suggested that both phenomena reflect limits of the attentional system and
      how attention is allocated when needing to organize stimuli for entrance into
      awareness, these two phenomena are dissociable; RB is not simply an enhanced AB.
      Furthermore, investigations of AB and RB have taken quite different courses over
      the last two decades. The AB has been investigated extensively with a variety of
      experimental, behavioral, neurophysiological, and clinical approaches, and has
      become widely used as a paradigm of convenience with which to study other
      effects. In contrast, studies of RB have tended to manipulate the nature of the
      target information to understand the level of representation that supports RB.
      WIREs Cogni Sci 2011 2 336-344 DOI: 10.1002/wcs.129 For further resources related
      to this article, please visit the WIREs website. 

PMID- 26302082
TI  - Genes and cognition.
AB  - Explaining individual differences in human cognition has been a prominent goal of
      psychological research during the last century. Converging lines of evidence from
      human and animal research have shown that these differences are under the
      influence of genetic factors. However, identifying the specific genes involved is
      not an easy task. The complexities of the human genome and of the definition of
      the concept of cognition itself are obvious reasons why understanding the
      genetics of cognitive abilities is so complicated. About 20,000 genes are thought
      to have an impact on the development and functionality of the brain and each and
      every one of these may in fact have an effect on information processing, and
      therefore on cognition. In addition, the concept of cognition itself is very
      broad and has often been the subject of intense debate. It is therefore important
      to provide a precise definition of the cognitive phenotype before analyzing the
      genetic influences acting on it. Furthermore, the genetics of cognition can be
      investigated by multiple approaches that can be applied not only to human, but
      also to animal research. An overview of these methods and some of the results
      obtained is provided in an attempt to highlight the multidisciplinary complexity
      of studying the genetic bases of human cognition. Furthermore, some directions
      for future studies are suggested, highlighting the importance of analyzing gene
      environment interactions and avoiding deterministic approaches. WIREs Cogni Sci
      2011 2 345-352 DOI: 10.1002/wcs.135 For further resources related to this
      article, please visit the WIREs website. 

PMID- 26302083
TI  - Transport Gap Opening and High On-Off Current Ratio in Trilayer Graphene with
      Self-Aligned Nanodomain Boundaries.
AB  - Trilayer graphene exhibits exceptional electronic properties that are of interest
      both for fundamental science and for technological applications. The ability to
      achieve a high on-off current ratio is the central question in this field. Here,
      we propose a simple method to achieve a current on-off ratio of 10(4) by opening
      a transport gap in Bernal-stacked trilayer graphene. We synthesized Bernal
      stacked trilayer graphene with self-aligned periodic nanodomain boundaries (NBs)
      on the technologically relevant vicinal cubic-SiC(001) substrate and performed
      electrical measurements. Our low-temperature transport measurements clearly
      demonstrate that the self-aligned periodic NBs can induce a charge transport gap
      greater than 1.3 eV. More remarkably, the transport gap of ~0.4 eV persists even
      at 100 K. Our results show the feasibility of creating new electronic
      nanostructures with high on-off current ratios using graphene on cubic-SiC. 

PMID- 26302084
TI  - The Presence of HLA-E-Restricted, CMV-Specific CD8+ T Cells in the Blood of Lung
      Transplant Recipients Correlates with Chronic Allograft Rejection.
AB  - The human cytomegalovirus (CMV) immune evasion protein, UL40, shares an identical
      peptide sequence with that found in the leader sequence of many human leukocyte
      antigen (HLA)-C alleles and when complexed with HLA-E, can modulate NK cell
      functions via interactions with the CD94-NKG2 receptors. However the UL40-derived
      sequence can also be immunogenic, eliciting robust CD8+ T cell responses. In the
      setting of solid organ transplantation these T cells may not only be involved in
      antiviral immunity but also can potentially contribute to allograft rejection
      when the UL40 epitope is also present in allograft-encoded HLA. Here we assessed
      15 bilateral lung transplant recipients for the presence of HLA-E-restricted UL40
      specific T cells by tetramer staining of peripheral blood mononuclear cells
      (PBMC). UL40-specific T cells were observed in 7 patients post-transplant however
      the magnitude of the response varied significantly between patients. Moreover,
      unlike healthy CMV seropositive individuals, longitudinal analyses revealed that
      proportions of such T cells fluctuated markedly. Nine patients experienced low
      grade acute cellular rejection, of which 6 also demonstrated UL40-specific T
      cells. Furthermore, the presence of UL40-specific CD8+ T cells in the blood was
      significantly associated with allograft dysfunction, which manifested as
      Bronchiolitis Obliterans Syndrome (BOS). Therefore, this study suggests that
      minor histocompatibility antigens presented by HLA-E can represent an additional
      risk factor following lung transplantation. 

PMID- 26302085
TI  - Sentiment Measured in Hospital Discharge Notes Is Associated with Readmission and
      Mortality Risk: An Electronic Health Record Study.
AB  - Natural language processing tools allow the characterization of sentiment--that
      is, terms expressing positive and negative emotion--in text. Applying such tools
      to electronic health records may provide insight into meaningful patient or
      clinician features not captured in coded data alone. We performed sentiment
      analysis on 2,484 hospital discharge notes for 2,010 individuals from a
      psychiatric inpatient unit, as well as 20,859 hospital discharges for 15,011
      individuals from general medical units, in a large New England health system
      between January 2011 and 2014. The primary measures of sentiment captured
      intensity of subjective positive or negative sentiment expressed in the discharge
      notes. Mean scores were contrasted between sociodemographic and clinical groups
      in mixed effects regression models. Discharge note sentiment was then examined
      for association with risk for readmission in Cox regression models. Discharge
      notes for individuals with greater medical comorbidity were modestly but
      significantly lower in positive sentiment among both psychiatric and general
      medical cohorts (p<0.001 in each). Greater positive sentiment at discharge was
      associated with significantly decreased risk of hospital readmission in each
      cohort (~12% decrease per standard deviation above the mean). Automated
      characterization of discharge notes in terms of sentiment identifies differences
      between sociodemographic groups, as well as in clinical outcomes, and is not
      explained by differences in diagnosis. Clinician sentiment merits investigation
      to understand why and how it reflects or impacts outcomes.

PMID- 26302086
TI  - Strong Facet-Induced and Light-Controlled Room-Temperature Ferromagnetism in
      Semiconducting beta-FeSi2 Nanocubes.
AB  - Crystalline beta-FeSi2 nanocubes with two {100} facets and four {011} lateral
      facets synthesized by spontaneous one-step chemical vapor deposition exhibit
      strong room-temperature ferromagnetism with saturation magnetization of 15 emu/g.
      The room-temperature ferromagnetism is observed from the beta-FeSi2 nanocubes
      larger than 150 nm with both the {100} and {011} facets. The ferromagnetism is
      tentatively explained with a simplified model including both the itinerant
      electrons in surface states and the local moments on Fe atoms near the surfaces.
      The work demonstrates the transformation from a nonmagnetic semiconductor to a
      magnetic one by exposing specific facets and the room-temperature ferromagnetism
      can be manipulated under light irradiation. The semiconducting beta-FeSi2
      nanocubes may have large potential in silicon-based spintronic applications. 

PMID- 26302087
TI  - Interplay between Lipid Interaction and Homo-coiling of Membrane-Tethered Coiled
      Coil Peptides.
AB  - The designed coiled-coil-forming peptides E [(EIAALEK)3] and K [(KIAALKE)3] are
      known to trigger efficient membrane fusion when they are tethered to lipid
      vesicles in the form of lipopeptides. Knowledge of their secondary structure is a
      key element in understanding their role in membrane fusion. Special conditions
      can be found at the interface of the membrane, where the peptides are confined in
      close proximity to other peptide molecules as well as to the lipid interface.
      Consequently, different structural states were proposed for the peptides when
      tethered to this interface. Due to the multitude of possible states, determining
      the structure solely on the basis of circular dichroism (CD) spectra at a single
      temperature can be misleading. In addition, it has not yet been possible to
      unambiguously distinguish between the membrane-bound and the coiled-coil states
      of these peptides by means of infrared (IR) spectroscopy due to their very
      similar amide I' bands. Here, the molecular basis of this similarity is
      investigated by means of site-specific (13)C-labeled FTIR spectroscopy.
      Structural similarities between the membrane-interacting helix of K and the homo
      coiled-coil-forming helix of E are shown to cause the similar spectroscopic
      properties. Furthermore, the peptide structure is investigated using temperature
      dependent CD and IR spectroscopy, and it is shown that the different states can
      be distinguished on the basis of their thermal behavior. It is shown that the two
      peptides behave fundamentaly differently when tethered to the lipid membrane,
      which implies that their role during membrane fusion is different and the
      mechanism of this process is asymmetric. 

PMID- 26302088
TI  - A Meta-Analysis of Preterm Infant Massage: An Ancient Practice With Contemporary
      Applications.
AB  - OBJECTIVE: To evaluate the efficacy of massage on the short- and long-term
      outcomes of preterm infants. METHODS: A search was conducted using the PRISMA
      framework. Validity of included studies was assessed using criteria defined by
      the Cochrane Collaboration that was carried out independently by two reviewers
      with a third reviewer to resolve differences. RESULTS: Thirty-four studies met
      the inclusion criteria, 3 were quasi-experimental, 1 was a pilot study, and the
      remaining 30 were randomized controlled trials (RCTs). The outcomes that could be
      used in the meta-analysis and found in more than three studies noted that massage
      improved daily weight gain by 0.53 g (95% CI = 0.28-0.78), p < 0.0001, and
      resulted in a significant improvement in mental scores by 7.89 points (95% CI =
      0.96-14.82), p < 0.03. There were no significant effects on length of hospital
      stay, caloric intake, or weight at discharge. Other outcomes were not analyzed
      either because the units of measurement varied or because means and standard
      deviations were not provided by the authors. These included vagal activity and
      heart rate variability (5 studies), neurobehavioral states (7 studies), pain
      responses (2 studies), maternal outcomes (2 studies), breastfeeding (2 studies),
      and physiologic parameters: bone formation (2 studies), immunologic markers (1
      study), brain maturity (1 study), and temperature (1 study). The quality of the
      studies was variable with methods of randomization and blinding of assessment
      unclear in 18 of the 34 studies. CONCLUSIONS: Massage therapy could be a
      comforting measure for infants in the NICU to improve weight gain and enhance
      mental development. However, the high heterogeneity, the weak quality in some
      studies, and the lack of a scientific association between massage and
      developmental outcomes preclude making definite recommendations and highlight the
      need for further RCTs to contribute to the existing body of knowledge.

PMID- 26302089
TI  - Hyaluronic Acid Engineered Nanomicelles Loaded with 3,4-Difluorobenzylidene
      Curcumin for Targeted Killing of CD44+ Stem-Like Pancreatic Cancer Cells.
AB  - Cancer stem-like cells (CSLCs) play a pivotal role in acquiring multidrug
      resistant (MDR) phenotypes. It has been established that pancreatic cancers
      overexpressing CD44 receptors (a target of hyaluronic acid; HA) is one of the
      major contributors for causing MDR. Therefore, targeted killing of CD44
      expressing tumor cells using HA based active targeting strategies may be
      beneficial for eradicating MDR-pancreatic cancers. Here, we report the synthesis
      of a new HA conjugate of copoly(styrene maleic acid) (HA-SMA) that could be
      engineered to form nanomicelles with a potent anticancer agent, 3,4
      difluorobenzylidene curcumin (CDF). The anticancer activity of CDF loaded
      nanomicelles against MiaPaCa-2 and AsPC-1 human pancreatic cancer cells revealed
      dose-dependent cell killing. Results of cellular internalization further
      confirmed better uptake of HA engineered nanomicelles in triple-marker positive
      (CD44+/CD133+/EpCAM+) pancreatic CSLCs compared with triple-marker negative (CD44
      /CD133-/EpCAM-) counterparts. More importantly, HA-SMA-CDF exhibited superior
      anticancer response toward CD44+ pancreatic CSLCs. Results further confirmed that
      triple-marker positive cells treated with HA-SMA-CDF caused significant reduction
      in CD44 expression and marked inhibition of NF-kappaB that in-turn can mitigate
      their proliferative and invasive behavior. Conclusively, these results suggest
      that the newly developed CD44 targeted nanomicelles may have great implications
      in treating pancreatic cancers including the more aggressive pancreatic CSLCs. 

PMID- 26302090
TI  - Consumption of White Rice and Brown Rice and Urinary Inorganic Arsenic
      Concentration.

PMID- 26302091
TI  - Inhibitory effect of natural organic matter or other background constituents on
      photocatalytic advanced oxidation processes: Mechanistic model development and
      validation.
AB  - The ability of reactive oxygen species (ROS) to interact with priority pollutants
      is crucial for efficient water treatment by photocatalytic advanced oxidation
      processes (AOPs). However, background compounds in water such as natural organic
      matter (NOM) can significantly hinder targeted reactions and removal efficiency.
      This inhibition can be complex, interfering with degradation in solution and at
      the photocatalyst surface as well as hindering illumination efficiency and ROS
      production. We developed an analytical model to account for various inhibition
      mechanisms in catalytic AOPs, including competitive adsorption of inhibitors,
      scavenging of produced ROS at the surface and in solution, and the inner
      filtering of the excitation illumination, which combine to decrease ROS-mediated
      degradation. This model was validated with batch experiments using a variety of
      ROS producing systems (OH-generating TiO2 photocatalyst and H2O2-UV; (1)O2
      generating photosensitive functionalized fullerenes and rose bengal) and
      inhibitory compounds (NOM, tert-butyl alcohol). Competitive adsorption by NOM and
      ROS scavenging were the most influential inhibitory mechanisms. Overall, this
      model enables accurate simulation of photocatalytic AOP performance when one or
      more inhibitory mechanisms are at work in a wide variety of application
      scenarios, and underscores the need to consider the effects of background
      constituents on degradation efficiency. 

PMID- 26302092
TI  - Clinical Features for Mild Hand, Foot and Mouth Disease in China.
AB  - BACKGROUND: Mild hand, foot and mouth disease (HFMD) is at a critical stage owing
      to its ease of communicability and a higher risk of developing severe
      complications and death. Clinical diagnosis of mild HFMD was made by the
      presenting symptoms and signs (symptoms in brief) alone. We aim to evaluate the
      frequencies of symptoms in a retrospective case series study. METHODS: We
      collected epidemiological, demographic, clinical, and laboratory data from
      outpatient and inpatient settings on the clinical data warehouse system. We
      principally described the frequencies of symptoms of mild HFMD. Correlations
      between symptoms with laboratory-confirmed cases were then analyzed. RESULTS: The
      clinical data warehouse system included 3649 probable cases, between 2010 and
      2012, of which 956 (26.20%) were laboratory confirmed. The peak incidence was
      identified in children 2 years of age. A total of 370 of the 956 laboratory
      confirmed cases (38.70%) were associated with enterovirus 71 (EV71). Logistic
      regression analysis adjusted for geographical variables, age, sex, month of
      onset, and time from onset to diagnosis showed that the clinical features
      constipation (P<0.0001; adjusted OR, 95%CI (2.99, 2.28-3.91)), and blisters
      (P<0.0001; adjusted OR, 95%CI (2.16, 1.82-2.56)) were positively correlated with
      the confirmed cases. CONCLUSIONS: This is the largest case series study,
      including all the guideline-mentioned symptoms of mild HFMD. Our findings suggest
      that blisters and constipation should be considered as potential warning signs
      while front-line clinicians manage surges of children diagnosed with mild HFMD
      during a pandemic.

PMID- 26302095
TI  - Low temperature structural studies of SrSnO3.
AB  - High resolution powder neutron diffraction measurements on polycrystalline SrSnO3
      between 8 and 350 K are described. SrSnO3 retains the orthorhombic Pbnm structure
      over this temperature range. Examination of the thermal expansion of the
      individual lattice parameters reveals an anomaly near 230 K that may reflect the
      presence of polar nanodomains associated with local disorder of the octahedral
      tilts. 

PMID- 26302094
TI  - Composition-Driven Phase Boundary and Piezoelectricity in Potassium-Sodium
      Niobate-Based Ceramics.
AB  - The piezoelectricity of (K,Na)NbO3 ceramics strongly depends on the phase
      boundary types as well as the doped compositions. Here, we systematically studied
      the relationships between the compositions and phase boundary types in (K,Na)
      (Nb,Sb)O3-Bi0.5Na0.5AO3 (KNNS-BNA, A=Hf, Zr, Ti, Sn) ceramics; then their
      piezoelectricity can be readily modified. Their phase boundary types are
      determined by the doped elements. A rhombohedral-tetragonal (R-T) phase boundary
      can be driven in the compositions range of 0.035<=BNH<=0.040 and
      0.035<=BNZ<=0.045; an orthorhombic-tetragonal (O-T) phase boundary is formed in
      the composition range of 0.005<=BNT<=0.02; and a pure O phase can be only
      observed regardless of BNS content (<=0.01). In addition, the phase boundary
      types strongly affect their corresponding piezoelectricities. A larger d33 (~440
      450 pC/N) and a higher d33* (~742-834 pm/V) can be attained in KNNS-BNA (A=Zr and
      Hf) ceramics due to the involvement of R-T phase boundary, and unfortunately KNNS
      BNA (A=Sn and Ti) ceramics possess a relatively poor piezoelectricity (d33<=200
      and d33*<600 pm/V) due to the involvement of other phase structures (O-T or O).
      In addition, the underlying physical mechanisms for the relationships between
      piezoelectricity and phase boundary types were also discussed. We believe that
      comprehensive research can design more excellent ceramic systems concerning
      potassium-sodium niobate.

PMID- 26302096
TI  - Development and evaluation of a Spanish-language version of the Relational Health
      Indices.
AB  - We reported the development and evaluation of a Spanish-language version of the
      Relational Health Indices (RHI; Liang et al., 2002) for use in clinical and
      research settings. Participants were 348 men and women from international (n =
      201) and domestic (n = 147) locations who were heritage Spanish speakers. A
      multistage translation of the RHI is described as well as the procedure used to
      evaluate the internal structure of the translated assessment. The results
      indicated a modest 3-factor structure, chi2(628) = 1397.16, p < .001; comparative
      fit index (CFI) = .86, Tucker-Lewis index (TLI) = .85, root mean square error of
      approximation (RMSEA) = .06 for the amigo (peer), mentor (mentor), and comunidad
      (community) subscales that has practical implications for treatment planning,
      outcome evaluation, and program development. Implications for counseling practice
      and future research are discussed. (PsycINFO Database Record

PMID- 26302093
TI  - Effect of Selective Mineralocorticoid Receptor Blockade on Flow-Mediated Dilation
      and Insulin Resistance in Older Adults with Metabolic Syndrome.
AB  - BACKGROUND: The prevalence of metabolic syndrome is especially high in older
      adults. Metabolic syndrome is associated with impaired vascular endothelial
      function, insulin resistance, and increased risk for cardiovascular disease but
      the underlying mechanisms are not fully elucidated. Plasma aldosterone is
      independently associated with metabolic syndrome and is linked to endothelial
      dysfunction and insulin resistance. Thus, we hypothesized that mineralocorticoid
      receptor (MR) blockade would improve flow-mediated dilation and insulin
      resistance in older adults with metabolic syndrome. METHODS: To test this
      hypothesis, we conducted a balanced, randomized, double-blind, placebo
      controlled, crossover study using selective MR blockade (eplerenone; 100 mg/day)
      for 1 month with 1 month washout in older adults with metabolic syndrome (62.6 +/
      3.2 yrs; mean +/- standard error). We evaluated brachial artery flow-mediated
      dilation (ultrasonography), oxidative stress (oxidized low-density lipoproteins
      and F2-isoprostanes) and insulin resistance (homeostatic model assessment).
      RESULTS: In response to MR blockade, flow-mediated dilation (5.37 +/- 0.85 vs.
      5.98 +/- 1.29%; placebo vs. eplerenone; P = 0.4), oxidized low-density
      lipoproteins (51.6 +/- 11.5 vs. 56.1 +/- 10.9 U/L; P = 0.6), and F2-isoprostanes
      (0.07 +/- 0.02 vs. 0.06 +/- 0.01 pg/mL; P = 0.3) did not improve. Insulin
      resistance also did not change following MR blockade (1.04 +/- 0.26 vs. 1.38 +/-
      0.50; P = 0.6). However, MR blockade resulted in a large reduction (10 mmHg) in
      systolic blood pressure (140 +/- 6 vs. 130 +/- 6 mmHg; P = 0.02), with no
      significant change in diastolic blood pressure (81 +/- 3 vs. 75 +/- 2 mmHg; P =
      0.2). CONCLUSIONS: Our data do not support a contributing role for MRs in
      endothelial dysfunction and insulin resistance in older adults with metabolic
      syndrome. However, our findings suggest MR activation is an important contributor
      to systolic hypertension in this patient group.

PMID- 26302097
TI  - What range of trait levels can the Autism-Spectrum Quotient (AQ) measure
      reliably? An item response theory analysis.
AB  - It has previously been noted that inventories measuring traits that originated in
      a psychopathological paradigm can often reliably measure only a very narrow range
      of trait levels that are near and above clinical cutoffs. Much recent work has,
      however, suggested that autism spectrum disorder traits are on a continuum of
      severity that extends well into the nonclinical range. This implies a need for
      inventories that can capture individual differences in autistic traits from very
      high levels all the way to the opposite end of the continuum. The Autism-Spectrum
      Quotient (AQ) was developed based on a closely related rationale, but there has,
      to date, been no direct test of the range of trait levels that the AQ can
      reliably measure. To assess this, we fit a bifactor item response theory model to
      the AQ. Results suggested that AQ measures moderately low to moderately high
      levels of a general autistic trait with good measurement precision. The reliable
      range of measurement was significantly improved by scoring the instrument using
      its 4-point response scale, rather than dichotomizing responses. These results
      support the use of the AQ in nonclinical samples, but suggest that items
      measuring very low and very high levels of autistic traits would be beneficial
      additions to the inventory. (PsycINFO Database Record

PMID- 26302098
TI  - The Strengths Assessment Inventory-Youth Version: An evaluation of the
      psychometric properties with male and female justice-involved youth.
AB  - Strengths constitute an important element of developmental assessments. It is
      consistent with evidence-based practice to use assessment tools that adequately
      measure a given construct and are appropriate for use with their targeted
      population. The Strengths Assessment Inventory-Youth Version (SAI-Y; Rawana &
      Brownlee, 2010)-a self-report measure of personal strengths, self-concept, and
      emotional functioning-was administered to 230 male and female adolescent
      offenders. Confirmatory factor analyses revealed that the SAI-Y's factor
      structure demonstrated an acceptable fit overall, while some factors fit the data
      well, and fewer factors displayed a questionable fit. A majority of scale scores
      were found to exhibit good reliability for both sexes, with three empirical scale
      scores demonstrating poor reliability. In addition, scores on the SAI-Y also
      achieved satisfactory convergent and divergent validity. Total strength scores
      were significantly correlated in the expected direction with most theoretically
      related measures of emotional and behavioral functioning (e.g., self-esteem,
      treatment readiness, antisocial attitudes). Lastly, moderate gender effects and
      small ethnicity differences in response patterns were found. This was the first
      validation study of the SAI-Y with a justice-involved sample and the results
      suggest it is an appropriate measure for use with both male and female justice
      involved young persons in detention and in the community. (PsycINFO Database
      Record

PMID- 26302099
TI  - Development and validation of the Adolescent Shame-Proneness Scale.
AB  - Like other self-conscious emotions, shame takes on particular significance during
      late childhood and adolescence because of a developing capacity for self
      reflection, self-other comparisons, and sensitivity to the views of others. Shame
      is a potentially important variable in adolescent well-being given its
      established associations with depression, reduced feelings of self-worth, and
      problematic anger. Three studies are reported that describe the development and
      validation of the Adolescent Shame-Proneness Scale (ASPS), a novel semi
      idiographic measure of shame-proneness. The ASPS is a 19-item measure assessing 3
      components of shame-proneness-negative self-evaluation, externalization, and
      emotional discomfort. Taken together, the studies support the reliability and
      validity of the ASPS as a semi-idiographic measure of shame-proneness in
      adolescents aged 11 to 18 years. ASPS scores correlate as expected with scores on
      existing measure of shame-proneness and with measures of anger, negative affect,
      and self-esteem. More important, the data suggest that ASPS scores are related
      to, but distinct from, guilt. Confirmatory factor analysis supported the validity
      of the ASPS factor structure (RMSEA = .08, SRMR = .05, CFI = .97, NNFI = .97).
      The ASPS represents a unique contribution to existing options for measuring shame
      proneness in research and clinical contexts. Further work is required to assess
      the ASPS' temporal stability and its viability and psychometric properties in
      more culturally diverse samples. (PsycINFO Database Record

PMID- 26302100
TI  - Text mining a self-report back-translation.
AB  - There are several recommendations about the routine to undertake when back
      translating self-report instruments in cross-cultural research. However, text
      mining methods have been generally ignored within this field. This work describes
      a text mining innovative application useful to adapt a personality questionnaire
      to 12 different languages. The method is divided in 3 different stages, a
      descriptive analysis of the available back-translated instrument versions, a
      dissimilarity assessment between the source language instrument and the 12 back
      translations, and an item assessment of item meaning equivalence. The suggested
      method contributes to improve the back-translation process of self-report
      instruments for cross-cultural research in 2 significant intertwined ways. First,
      it defines a systematic approach to the back translation issue, allowing for a
      more orderly and informed evaluation concerning the equivalence of different
      versions of the same instrument in different languages. Second, it provides more
      accurate instrument back-translations, which has direct implications for the
      reliability and validity of the instrument's test scores when used in different
      cultures/languages. In addition, this procedure can be extended to the back
      translation of self-reports measuring psychological constructs in clinical
      assessment. Future research works could refine the suggested methodology and use
      additional available text mining tools. (PsycINFO Database Record

PMID- 26302101
TI  - "False feigners": Examining the impact of non-content-based invalid responding on
      the Minnesota Multiphasic Personality Inventory-2 Restructured Form content-based
      invalid responding indicators.
AB  - Misinterpretation of non-content-based invalid (e.g., random, fixed) responding
      as overreporting or underreporting is likely to adversely impact test
      interpretation and could bias inferences about examinee intentions. We examined
      the impact of non-content-based invalid responding on the following Minnesota
      Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF) content-based
      invalid responding indicators: Infrequent Responses (F-r), Infrequent
      Psychopathology Responses (FP-r), Infrequent Somatic Responses (FS), Symptom
      Validity (FBS-r), Response Bias Scale (RBS), Uncommon Virtues (L-r), and
      Adjustment Validity (K-r). In 4 samples from which invalid responders were
      excluded, we systematically inserted increasing percentages of random,
      acquiescent, or counter-acquiescent item responses ranging from 0% to 100% and
      examined the impact that non-content-based invalid response styles had on the
      content-based invalid responding indicators. F-r, FP-r, FS, RBS, and L-r were
      susceptible to non-content-based invalid responding, whereas FBS-r and K-r were
      unaffected. Individuals with Variable Response Inconsistency (VRIN-r) and True
      Response Inconsistency (TRIN-r) elevations were removed, and the frequencies of
      content-based invalid responding elevations were then reexamined for false
      indications of feigning. Findings were consistent across samples and emphasize
      the need to screen for non-content-based invalid responding before screening for
      content-based invalid responding in the assessment of personality and
      psychopathology. VRIN-r and TRIN-r were useful in detecting most-but not all
      cases of non-content-based invalid responding. A small but meaningful percentage
      of the remaining individuals were misclassified as overreporters (i.e., false
      feigners) by FP-r and FS. Clinicians should interpret FP-r and FS with some
      caution in the presence of moderate levels of non-content-based invalid
      responding. Post hoc examinations of scale characteristics indicated that the
      most susceptible scales were brief, consisted of rarely endorsed items, included
      a relatively high percentage of true-keyed items, and required a low percentage
      of endorsed items to reach clinical significance. (PsycINFO Database Record

PMID- 26302102
TI  - The EPOCH Measure of Adolescent Well-Being.
AB  - We introduce the EPOCH Measure of Adolescent Well-Being, which assesses 5
      positive psychological characteristics (Engagement, Perseverance, Optimism,
      Connectedness, and Happiness) that might foster well-being, physical health, and
      other positive outcomes in adulthood. To create the measure, a pool of 60 items
      was compiled, and a series of 10 studies with 4,480 adolescents (age 10-18) from
      the United States and Australia were used to develop and test the measure,
      including the factor structure, internal and test-retest reliability, and
      convergent, discriminant, and predictive validity. The final 20-item measure
      demonstrated adequate psychometric properties, although additional studies are
      needed to further validate the measure, extend to other population groups, and
      examine the extent to which it predicts long-term outcomes. As a brief
      multidimensional measure, the EPOCH measure contributes to the empirical testing
      and application of well-being theory, and offers a valuable addition to batteries
      designed to assess adolescent positive psychological functioning. (PsycINFO
      Database Record

PMID- 26302103
TI  - Validation of the Spanish Version of the Young Adult Alcohol Consequences
      Questionnaire (S-YAACQ).
AB  - The present work was aimed at analyzing the psychometric properties of a Spanish
      version of the 48-item Young Adult Alcohol Consequences Questionnaire (YAACQ) by
      applying the item response theory. Participants were 247 college students (75.7%
      female) who reported drinking alcohol within the last 3 months. The 48-item YAACQ
      was translated into Spanish and back to English. The psychometric properties of
      the Spanish YAACQ (S-YAACQ) were analyzed applying the Rasch model, as well as
      group difference and correlational analyses. Factor structure of the S-YAACQ was
      analyzed using confirmatory factor analysis. The verification of the global fit
      of the data showed adequate indexes for persons and items. The reliability
      estimates for the items and the persons were both high. Scores on the S-YAACQ
      were strongly correlated with scores on the Spanish versions of the AUDIT and the
      RAPI and with frequency of binge drinking. Five of 48 items showed different item
      functioning (DIF) as a function of gender. These biases were in opposite
      directions, resulting in DIF cancellation. The item severity continuum was
      largely similar to that found with the Spanish brief YAACQ and to that found in
      U.S. and Dutch samples. Overall, results from the present study suggest that this
      translated full version is better suited than the brief YAACQ for the
      identification of youth who are experiencing problems with alcohol. Findings
      suggest that the Spanish version of the full YAACQ may be used to identify a
      broad diversity of alcohol-related problems in Spanish-speaking college students.
      (PsycINFO Database Record

PMID- 26302105
TI  - The importance of assessing clinical phenomena in Mechanical Turk research.
AB  - Amazon.com's Mechanical Turk (MTurk) website provides a data collection platform
      with quick and inexpensive access to diverse samples. Numerous reports have
      lauded MTurk as capturing high-quality data with an epidemiological sample that
      is more representative of the U.S. population than traditional in-person
      convenience samples (e.g., undergraduate subject pools). This benefit, in
      combination with the ease and low-cost of data collection, has led to a
      remarkable increase in studies using MTurk to investigate phenomena across a wide
      range of psychological disciplines. Multiple reports have now examined the
      demographic characteristics of MTurk samples. One key gap remains, however, in
      that relatively little is known about individual differences in clinical symptoms
      among MTurk participants. This paper discusses the importance of assessing
      clinical phenomena in MTurk samples and supports its assertions through an
      empirical investigation of a large sample (N = 1,098) of MTurk participants.
      Results revealed that MTurk participants endorse clinical symptoms to a
      substantially greater degree than traditional nonclinical samples. This
      distinction was most striking for depression and social anxiety symptoms, which
      were endorsed at levels comparable with individuals with clinically diagnosed
      mood and anxiety symptoms. Participants' symptoms of physiological anxiety,
      hoarding, and eating pathology fell within the subclinical range. Overall, the
      number of individuals exceeding validated clinical cutoffs was between 3 and 19
      times the estimated 12-month prevalence rates. Based on the current findings, it
      is argued that MTurk participants differ from the general population in
      meaningful ways, and researchers should consider this when referring to this
      sample as truly representative. (PsycINFO Database Record

PMID- 26302104
TI  - Psychometric properties of the Barkley Deficits in Executive Functioning Scale: A
      Spanish-Language Version in a community sample of puerto rican adults.
AB  - Performance-based measures have shown some limitation in the assessment of
      executive functioning (EF) and rating scales have been proposed as an
      alternative. Our aim was to conduct a comprehensive psychometric evaluation of
      the Barkley Deficits in Executive Functioning Scale (BDEFS), as administered in
      452 Latino community adults (65.5% female). The BDEFS was back-translated into
      Spanish. We performed exploratory factor analysis (EFA) to assess the structure
      of the translated BDEFS and to compare it with the original five-factor structure
      based on the English-language version. Confirmatory factor analysis (CFA) was
      performed to test the original language structure of the instrument, and also a
      modified version with items that loaded equally in both versions. The Adult Self
      Report Scale was used to screen for ADHD symptoms. We assessed invariance on the
      latent factor's mean by age and gender, and to estimate associations with ADHD
      symptom dimensions. The five-factor structure of the BDEFS was partially
      supported by EFA/CFA, in which 78 out of 89 items loaded similar to the original
      English-language structure. Factor scores were significantly associated with ADHD
      symptom dimensions. Model-based contrasts revealed that inattention was primarily
      associated with disorganization, time-management and motivational aspects of EF;
      hyperactivity was predominantly related to self-restraint and self-regulation
      factors. The BDEFS seemingly assesses similar dimensions of the EF construct in
      English and in the present Spanish-language versions. Factor scores were
      differentially associated with ADHD subtypes. Replication and confirmation of the
      Spanish-language BDEFS in a larger sample is advised. (PsycINFO Database Record

PMID- 26302107
TI  - The Youth Psychopathic Traits Inventory-Short Version in a general population
      sample of emerging adults.
AB  - Prior studies with children and adolescents have shown that Youth Psychopathic
      Traits Inventory-Short Version (YPI-S) scores are internally consistent and
      manifest expected relations with external variables of interest. In the present
      study, the factor structure and the internal consistency of YPI-S scores, and the
      convergent validity of the interpretation of YPI-S scores were tested in a sample
      of 2,500 emerging adults from the general population in Sweden (aged 20-24 years;
      52.6% women). Results of exploratory and confirmatory factor analyses support a 3
      factor structure among both men and women that is similar to prior YPI-S studies
      conducted with children and adolescents. The YPI-S total score and the 3 factor
      scores were internally consistent. Correlations with external variables,
      including aggression and delinquency, support the convergent validity of the
      interpretation of YPI-S scores. Finally, the strength of these zero-order and
      partial correlations, overall, was not significantly different across gender. In
      conclusion, this study provides initial evidence that the YPI-S may hold promise
      as a brief and time-effective self-report tool for assessing psychopathic traits
      in emerging adults. The present findings also suggest that the YPI-S performs in
      a consistent manner across gender. Recommendations for future research with the
      YPI-S are discussed. (PsycINFO Database Record

PMID- 26302108
TI  - Correction to Castillo et al. (2015).
AB  - Reports an error in "Factor Structure and Factorial Invariance of the
      Multidimensional Acculturative Stress Inventory" by Linda G. Castillo, Miguel A.
      Cano, Myeongsun Yoon, Eunju Jung, Elissa J. Brown, Byron L. Zamboanga, Su Yeong
      Kim, Seth J. Schwartz, Que-Lam Huynh, Robert S. Weisskirch and Susan Krauss
      Whitbourne (Psychological Assessment, Advanced Online Publication, Mar 2, 2015,
      np). The institutional affiliation for Seth J. Schwartz was incorrectly listed as
      Miami University. Seth J. Schwartz is at the University of Miami. All versions of
      this article have been corrected. (The following abstract of the original article
      appeared in record 2015-08361-001.) Using a national data set, this study
      examined the factor structure and factorial invariance of the Multidimensional
      Acculturative Stress Inventory (MASI) across Latino and Asian Americans, gender,
      and nativity (U.S.- vs. foreign-born). Results showed that a 4-factor model of
      acculturative stress provided good fit to the data. Tests of factorial invariance
      provided evidence of measurement equivalence across all of the groupings tested.
      These findings suggest that the MASI operationalizes acculturative stress in an
      equivalent manner across Latino and Asian American students, gender, and
      nativity.

PMID- 26302106
TI  - Revising the BIS/BAS Scale to study development: Measurement invariance and
      normative effects of age and sex from childhood through adulthood.
AB  - Carver and White's (1994) Behavioral Inhibition System/Behavioral Activation
      System (BIS/BAS) Scales have been useful tools for studying individual
      differences in reward-punishment sensitivity; however, their factor structure and
      invariance across development have not been well tested. In the current study, we
      examined the factor structure of the BIS/BAS Scales across 5 age groups: 6- to 10
      year-old children (N = 229), 11- to 13-year-old early adolescents (N = 311), 14-
      to 16-year-old late adolescents (N = 353), 18- to 22-year-old young adults (N =
      844), and 30- to 45-year-old adults (N = 471). Given poor fit of the standard 4
      factor model (BIS, Reward Responsivity, Drive, Fun Seeking) in the literature, we
      conducted exploratory factor analyses in half of the participants and identified
      problematic items across age groups. The 4-factor model showed poor fit in our
      sample, whereas removing the BAS Fun Seeking subscale and problematic items from
      the remaining subscales improved fit in confirmatory factor analyses conducted
      with the second half of the participants. The revised model showed strict
      invariance across age groups and by sex, indicating consistent factor structure,
      item loadings, thresholds, and unique or residual variances. Additionally, in our
      cross-sectional data, we observed nonlinear relations between age and subscale
      scores, where scores tended to be higher in young adulthood than in childhood and
      later adulthood. Furthermore, sex differences emerged across development;
      adolescent and adult females had higher BIS scores than males in this age range,
      whereas sex differences were not observed in childhood. These differences may
      help us to understand the rise in internalizing psychopathology in adolescence,
      particularly in females. Future developmental studies are warranted to examine
      the impact of rewording problematic items.

PMID- 26302109
TI  - Gait Monitoring for Early Neurological Disorder Detection Using Sensors in a
      Smartphone: Validation and a Case Study of Parkinsonism.
AB  - BACKGROUND: Diagnosing brain disorders, such as Parkinson's disease (PD) or
      Alzheimer's disease, is often difficult, especially in the early stages.
      Moreover, it has been estimated that nearly 40% of people with PD may not be
      diagnosed. Traditionally, the diagnosis of neurological disorders, such as PD,
      often required a doctor to observe the patient over time to recognize signs of
      rigidity in movement. MATERIALS AND METHODS: The pedestrian dead reckoning (PDR)
      system is a self-contained technique that has been widely used for indoor
      localization. In this work we propose a PDR-based method to continuously monitor
      and record the patient's gait characteristics using a smartphone. Seventeen
      patients were studied over a period of 1 year. During the year it became apparent
      that 1 of the patients was actually developing PD. To the best of our knowledge,
      our work is the first attempt to use sensors in a smartphone to help identify
      patients in their early stages of neurological disease. RESULTS: On average, the
      accuracy of our step length estimation was about 98%. Using a binary
      classification method-namely, support vector machine-we carried out a case study
      and showed that it was feasible to identify changes in the walking patterns of a
      PD patient with an accuracy of 94%. CONCLUSIONS: Using 1 year of gait trace data
      obtained from the users' phones, our work provides a first step to experimentally
      show the possibility of applying smartphone sensor data to provide early warnings
      to potential PD patients to encourage them to seek medical assistance and thus
      help doctors diagnose this disease earlier.

PMID- 26302110
TI  - Perospirone Exhibits Antiemetic Efficacy against Opioid-Induced Nausea in
      Patients with Advanced Cancer.

PMID- 26302112
TI  - BMP4 and BMP7 Suppress StAR and Progesterone Production via ALK3 and SMAD1/5/8
      SMAD4 in Human Granulosa-Lutein Cells.
AB  - Adequate production of progesterone by the corpus luteum is critical to the
      successful establishment of pregnancy. In animal models, bone morphogenetic
      protein (BMP) 4 and BMP7 have been shown to suppress either basal or gonadotropin
      induced progesterone production, depending on the species examined. However, the
      effects of BMP4 and BMP7 on progesterone production in human granulosa cells are
      unknown. In the present study, we used immortalized (SVOG) and primary human
      granulosa-lutein cells to investigate the effects of BMP4 and BMP7 on
      steroidogenic acute regulatory protein (StAR) expression and progesterone
      production and to examine the underlying molecular mechanism. Treatment of
      primary and immortalized human granulosa cells with recombinant BMP4 or BMP7
      decreased StAR expression and progesterone accumulation. In SVOG cells, the
      suppressive effects of BMP4 and BMP7 on StAR expression were blocked by
      pretreatment with inhibitors of activin receptor-like kinase (ALK)2/3/6
      (dorsomorphin) or ALK2/3 (DMH1) but not ALK4/5/7 (SB-431542). Moreover, small
      interfering RNA-mediated depletion of ALK3, but not ALK2 or ALK6, reversed the
      effects of BMP4 and BMP7 on StAR expression. Likewise, BMP4- and BMP7-induced
      phosphorylation of SMAD 1/5/8 was reversed by treatment with DMH1 or small
      interfering RNA targeting ALK3. Knockdown of SMAD4, the essential common SMAD for
      BMP/TGF-beta signaling, abolished the effects of BMP4 and BMP7 on StAR
      expression. Our results suggest that BMP4 and BMP7 down-regulate StAR and
      progesterone production via ALK3 and SMAD1/5/8-SMAD4 signaling in human granulosa
      lutein cells. 

PMID- 26302111
TI  - KNDy Neurons Modulate the Magnitude of the Steroid-Induced Luteinizing Hormone
      Surges in Ovariectomized Rats.
AB  - Kisspeptin is the most potent stimulator of LH release. There are two kisspeptin
      neuronal populations in the rodent brain: in the anteroventral periventricular
      nucleus (AVPV) and in the arcuate nucleus. The arcuate neurons coexpress
      kisspeptin, neurokinin B, and dynorphin and are called KNDy neurons. Because
      estradiol increases kisspeptin expression in the AVPV whereas it inhibits KNDy
      neurons, AVPV and KNDy neurons have been postulated to mediate the positive and
      negative feedback effects of estradiol on LH secretion, respectively. Yet the
      role of KNDy neurons during the positive feedback is not clear. In this study,
      ovariectomized rats were microinjected bilaterally into the arcuate nucleus with
      a saporin-conjugated neurokinin B receptor agonist for targeted ablation of
      approximately 70% of KNDy neurons. In oil-treated animals, ablation of KNDy
      neurons impaired the rise in LH after ovariectomy and kisspeptin content in both
      populations. In estradiol-treated animals, KNDy ablation did not influence the
      negative feedback of steroids during the morning. Surprisingly, KNDy ablation
      increased the steroid-induced LH surges, accompanied by an increase of kisspeptin
      content in the AVPV. This increase seems to be due to lack of dynorphin input
      from KNDy neurons to the AVPV as the following: 1) microinjections of a dynorphin
      antagonist into the AVPV significantly increased the LH surge in estradiol
      treated rats, similar to KNDy ablation, and 2) intra-AVPV microinjections of
      dynorphin in KNDy-ablated rats restored LH surge levels. Our results suggest that
      KNDy neurons provide inhibition to AVPV kisspeptin neurons through dynorphin and
      thus regulate the amplitude of the steroid-induced LH surges. 

PMID- 26302113
TI  - The cortisol response to ACTH in pigs, heritability and influence of
      corticosteroid-binding globulin.
AB  - In the search for biological basis of robustness, this study aimed (i) at the
      determination of the heritability of the cortisol response to ACTH in juvenile
      pigs, using restricted maximum likelihood methodology applied to a multiple trait
      animal model, and (ii) at the study of the relationships between basal and
      stimulated cortisol levels with corticosteroid-binding globulin (CBG), IGF-I and
      haptoglobin, all important players in glucose metabolism and production traits.
      At 6 weeks of age, 298 intact male and female piglets from 30 litters (30 dams
      and 30 boars) were injected with 250 ug ACTH(1-24) (Synacthen). Blood was taken
      before ACTH injection to measure basal levels of cortisol, glucose, CBG, IGF-I
      and haptoglobin, and 60 min later to measure stimulated cortisol levels and
      glucose. Cortisol increased 2.8-fold after ACTH injection, with a high
      correlation between basal and stimulated levels (phenotypic correlation, r
      p=0.539; genetic correlation, r g=0.938). Post-ACTH cortisol levels were highly
      heritable (h 2=0.684) and could therefore be used for genetic selection of
      animals with a more reactive hypothalamic-pituitary-adrenocortical axis. CBG
      binding capacity correlated with cortisol levels measured in basal conditions in
      males only. No correlation was found between CBG binding capacity and post-ACTH
      cortisol levels. Basal IGF-I concentration was positively correlated with BW at
      birth and weaning, and showed a high correlation with CBG binding capacity with a
      strong sexual dimorphism, the correlation being much higher in males than in
      females. Basal haptoglobin concentrations were negatively correlated with CBG
      binding capacity and IGF-I concentrations. Complex relationships were also found
      between circulating glucose levels and these different variables that have been
      shown to be related to glucose resistance in humans. These data are therefore
      valuable for the genetic selection of animals to explore the consequences on
      production and robustness traits, but also point at pigs as a relevant model to
      explore the underlying mechanisms of the metabolic syndrome including the
      contribution of genetic factors. 

PMID- 26302114
TI  - Metabolomics strategy reveals therapeutical assessment of limonin on nonbacterial
      prostatitis.
AB  - Limonin has been found to possess significant anti-inflammatory properties in
      animal tests and with, human cells, however, its precise metabolism mechanism has
      not been well explored. The aim of this study was to investigate the anti
      inflammatory effects of limonin in a nonbacterial prostatitis (NBP) animal model.
      Global metabolite profiling was performed by ultra-high-performance liquid
      chromatography combined with time-of-flight mass spectrometry (UPLC/ESI-TOFMS)
      and in conjunction with multivariate data analysis and pathway analysis which
      were integrated to explore differentiating metabolites and clarify the mechanism
      of limonin against capsaicin-induced NBP. Limonin has a potential protective
      function revealed by the metabolic profiling of limonin-treated rats located
      closer to the normal group. Twenty potential biomarker candidates and several key
      metabolic pathways contributing to the treatment of NBP were discovered and
      identified. Among the pathways, the related glycine, serine and threonine
      metabolism, glycerophospholipid metabolism were acutely perturbed. The changes in
      metabolites were restored to their base-line levels after limonin treatment,
      which might be through regulating the perturbed pathways to the normal state. The
      results indicate that changed biomarkers and pathways may provide evidence and
      insight into limonin action mechanisms and enable us to increase research
      productivity toward metabolomics in therapeutical assessment and drug discovery. 

PMID- 26302115
TI  - [Leprosy in Yucatan, retrospective clinical study of 63 years (1950-2013)].

PMID- 26302116
TI  - [Healthy fitness and cardiovascular risk in youth with intellectual
      disabilities].

PMID- 26302117
TI  - Regarding articles about Cali Cancer Registry I.

PMID- 26302118
TI  - Regarding articles about Cali Cancer Registry 2.

PMID- 26302119
TI  - Response to Dr. de Vries.

PMID- 26302120
TI  - [Primary caregiver burden as a risk factor for falls in geriatric patients].

PMID- 26302121
TI  - [Proposal for a new model to analyze an ancient myth: does the moon influence the
      frequency of births?].

PMID- 26302122
TI  - [Control of Aedes aegypti breeding sites with the program Recicla por tu
      bienestar in Merida, Mexico].
AB  - OBJECTIVES: To determine the importance of Ae. aegypti breeding-sites in
      Merida;to evaluate the impact of Recicla por tu bienestar (RxB, a recycling
      program) on the reduction of breeding sites and the perception of participants.
      MATERIALS AND METHODS: The relative importance for pupae production of the
      different types of breeding-sites was determined. Pre-and post-RxB entomological
      surveys were performed in participant neighborhoods to evaluate the impact on
      total containers and positive breeding-sites. A survey on the perception of
      participating people about dengue prevention and control and RxB was applied.
      RESULTS: Buckets/pots and "small diverse items" were the most important breeding
      sites. RxB had a significant impact in the reduction of total containers (IRR =
      0.74), positive containers (IRR = 0.33) and the risk of a house being positive
      for Ae. aegypti (OR = 0.41). All the interviewed participants referred RxB as
      needed and most consider it useful. CONCLUSIONS: RxB should be considered as a
      good practice for the dengue vector control.

PMID- 26302123
TI  - [Growth and survival of total and pathogenic Vibrio parahaemolyticus in American
      oyster (Crassostrea virginica) under cold storage].
AB  - OBJECTIVE: To quantify Vibrio parahaemolyticus densities in American oyster
      (Crassostrea virginica) under cold storage. MATERIALS AND METHODS: 320 oysters
      were stored at 7 degrees C for nine days and total and pathogenic densities were
      determined by the NMP-PCR methodology. RESULTS: V. parahaemolyticus tlh+
      densities were observed on 0,3, and 6 days of storage at 1.134, 2.764 and 0.785
      log10NMP/g, respectively, and pathogenic density trh+ on 0 and 3 days at 0.477
      and 0.519 log10NMP/g, respectively; the pathogenic densities tdh+ (0.519
      log10NMP/g), tdh+/trh+ (0.519 log10NMP/g), and tdh+orf8+ (-0.444 log10NMP/g) were
      detected on day 3 of storage. CONCLUSION: The results suggest that V.
      parahaemolyticus growth and pathogenic genes occurrence at 7 degrees C involve
      changes in the genetic expression as a cold shock response, favoring V.
      parahaemolyticus survival and virulence, representing a health risk.

PMID- 26302124
TI  - [Individual and family factors associated with depressive symptomatology in
      adolescents from public schools of Mexico].
AB  - OBJECTIVE: To estimate the prevalence of depressive symptoms (DS) and to explore
      associated individual and family factors in high-school students from public
      schools of Mexico. MATERIALS AND METHODS: Cross-sectional study of a
      representative sample of 9 982 students aged between 14 and 19 years. Logistic
      regression models were used to estimate odds ratio (OR) with 95% confidence
      interval (CI95%). RESULTS: 27% of students presented DS, with higher proportion
      among women (34%) than among men (18%). Factors associated with DS were being
      female (OR=2.25 CI95% 1.86-2.71); low self-esteem (OR=2.77 CI95% 2.41 -3.19);
      consuming alcohol (OR= 1.72 CI95% 1.46-2.02), consuming tobacco (OR= 1.57 CI95%
      1.31-1.88), consuming illegal drugs (OR=1.63 CI95% 1.29-2.05), domestic violence
      (OR=2.05 CI95% 1.77-2.39), and low communication between parents and their
      children (OR=1.78 CI95% 1.59-2.00). CONCLUSIONS: Depressive symptomatology among
      high-school students in Mexico is a public health issue.There is a need for
      intervention programs aimed at tackling the associated risk factors.

PMID- 26302126
TI  - [Balanced scorecard in health].
AB  - OBJECTIVE: To evaluate the installation of strategies in the higher complexity
      hospitals (HMC, in Spanish) of public health in Chile starting from the results
      of the Balanced Scorecard (BSC), during the years 2011-2012. MATERIALS AND
      METHODS: The implementation of the BSC is described, the strategies and
      indicators identified, and the results of the 57 HMC compared and analyzed.
      RESULTS: Starting from the comparison of the results it is discovered that the
      BSC allows to evaluate the installation of the strategies. CONCLUSION:
      Differences are identified in the installation of the strategies by geographical
      area, with North presenting a higher score (20.21), followed by Center (10.41)
      and South (19.50), which can be explained by the size and complexity of this
      establishments, variables that should be incorporated in the evaluation of the
      results of the BSC.

PMID- 26302125
TI  - [Mental health of undocumented migrants in transit at the southern border of
      Mexico].
AB  - OBJECTIVE: To identify the perception and needs in mental health of Central
      American migrants in transit through Tapachula, Chiapas. MATERIALS AND METHODS:
      Qualitative study in a migrant shelter in Tapachula, Chiapas. In 20 semi
      structured interviews with migrant men and women, we explored their perceptions
      on mental health and expectations on care. We used basic notions of phenomenology
      to guide the analysis. RESULTS: Migrants had several mental health problems
      related to the conditions at their country of origin and due to their initial
      transit through Mexico.Their perception on mental health problems was heavily
      influenced by the biomedical health paradigm. The expectations they had on the
      provision of services were related to the satisfaction of basic needs.
      CONCLUSIONS: It is necessary to strengthen the governmental response to mental
      health needs through collaborative strategies. Also, actions are needed to
      further the understanding of mental health in order to transcend the biomedical
      notions that stigmatize, segregate and create a barrier to accessing services.

PMID- 26302127
TI  - [Barriers and facilitators for physical activity during pregnancy and postpartum
      in women living in poverty of Mexico].
AB  - OBJECTIVE: To explore perceptions of healthcare providers and beneficiaries of
      Oportunidades program on physical activity during pregnancy and post-partum; and
      identify current reported practices related to counseling on physical activity in
      the primary healthcare services in Mexico. MATERIALS AND METHODS: A mixed methods
      approach was used which is part of a nutrition intervention of the Oportunidades
      program. Qualitative information was collected through interviews (50=women;
      34=providers) and quantitative information was collected by questionnaires (n=88
      women; n=64 provider; n=111 observations during consultation). RESULTS: The main
      barriers were: a) individual (lack of time and social support to childcare); b)
      sociocultural (gender bias derived from peer groups or family and lack of
      instructors), and c) environmental (lack of safe and adequate physical places).
      Only 38% of beneficiary women reported having been counseled on physical activity
      vs 63.4% of providers who reported having counseled on physical activity
      (p=0.002). CONCLUSION: There is a need to train healthcare providers and to
      promote physical activity during pregnancy and post-partum for reducing
      associated biases.

PMID- 26302128
TI  - [Influence of HIV related stigma on health care access].
AB  - OBJECTIVE: To notice the influence of the stigma surrounding HIV on the access to
      health services among the seropositive population of Medellin, Colombia, in 2012.
      MATERIALS AND METHODS: A qualitative approach using Strauss' and Corbin's
      grounded theory. Data was collected through 13 interviews at two different
      moments.These interviews were transcribed and analyzed, and the data found in
      them was processed via axial and open coding. RESULTS: The myths surrounding HIV
      become a barrier preventing access to healthcare;this hinders timely treatment of
      the virus. CONCLUSION: Government policies must aim to reduce the effect that the
      historical discrimination against HIV has generated so that it can guarantee that
      infected individuals have early access to treatments for this condition as well
      as health promotion services.

PMID- 26302129
TI  - [Use of lead-glazed ceramic as a source of exposure in children of marginalized
      indigenous zones of Oaxaca, Mexico].
AB  - OBJECTIVE: To find out whether the use of lead-glazed ceramic (LGC) is associated
      with blood lead levels in indigenous schoolchildren from Oaxaca, Mexico.
      MATERIALS AND METHODS: We evaluated LGC use at home as a primary source of lead
      exposure in 387 indigenous schoolchildren in Oaxaca in May 2001. RESULTS: We
      found an adjusted difference of 3.9MUg/dl (p<0.01) in blood lead levels (BLL)
      among children reporting to use (82%) LGC at home vs those who didn't. BL levels
      greater or equal than 10 and 20 MUg/dl were observed in 60 and 27% of children,
      respectively. CONCLUSIONS: Lead poisoning from LGC use could remain a concern for
      public health in Mexico, where there is a need to provide care and further study
      to verify its effect on BLL.

PMID- 26302130
TI  - Effectiveness of intervention programs in primary care for the robust elderly.
AB  - OBJECTIVE: This study aimed to search the literature for intervention programs in
      primary care with a multiprofes-sional character, specifically directed at the
      robust elderly, and with viable and cost-effective interventions. MATERIALS AND
      METHODS: The search strategies were applied in Cochrane, Lilacs, Pubmed, Scopus,
      WHOLIS, Embase, Medcarib, SciELO, Web of Science, and PAHO databases. RESULTS: 3
      665 articles were found and 32 remained for analysis, grouped into four
      categories: care management; multidisciplinary intervention; interventions on the
      basis of risk; and educational interventions with health professionals.
      CONCLUSION: Strategies such as domestic interventions can promote health and
      functionality of elderlies, as well as reduce mortality, use of the health system
      and costs. Besides that, the use of hard and light-hard technologies are
      important for risk prevention and care management for the elderly.There is a need
      to create programs for risk prevention and effective management of elderly care
      at the primary level.

PMID- 26302131
TI  - [Organizational capacity for continuous improvement of health services].
AB  - While the Mexican health system has achieved significant progress, as reflected
      in the growing improvement in population health, heterogeneity in the quality of
      services and its impact on health in different population groups is still a
      challenge. The costs or poor quality represent about 20 to 40% of the health
      system's expenditure. We need to develop organizational capacity to implement
      quality management systems in order to identify, evaluate, prevent and eventually
      overcome the health system's challenges. A competency-based comprehensive
      strategy for training human resources is proposed including undergraduate and
      graduate education as well as continuing education, which will contribute to
      improve the quality function at the various levels of responsibility in the
      health system. The proposed strategy responds to the context of the Mexican
      health system, but it could be adapted to other systems and contexts. 

PMID- 26302132
TI  - [Health in every policy: Prevention and control of non-communicable chronic
      diseases].

PMID- 26302133
TI  - [The burden of disease in Mexico, 1990-2010: New results and challenges].

PMID- 26302134
TI  - Enhanced Salt Removal in an Inverted Capacitive Deionization Cell Using Amine
      Modified Microporous Carbon Cathodes.
AB  - Microporous SpectraCarb carbon cloth was treated using nitric acid to enhance
      negative surface charges of COO(-) in a neutral solution. This acid-treated
      carbon was further modified by ethylenediamine to attach -NH2 surface functional
      groups, resulting in positive surface charges of -NH3(+) via pronation in a
      neutral solution. Through multiple characterizations, in comparison to pristine
      SpectraCarb carbon, amine-treated SpectraCarb carbon displays a decreased
      potential of zero charge but an increased point of zero charge, which is opposed
      to the effect obtained for acid-treated SpectraCarb carbon. An inverted
      capacitive deionization cell was constructed using amine-treated cathodes and
      acid-treated anodes, where the cathode is the negatively polarized electrode and
      the anode is the positively polarized electrode. Constant-voltage switching
      operation using NaCl solution showed that the salt removal capacity was
      approximately 5.3 mg g(-1) at a maximum working voltage of 1.1/0 V, which is an
      expansion in both the salt capacity and potential window from previous i-CDI
      results demonstrated for carbon xerogel materials. This improved performance is
      accounted for by the enlarged cathodic working voltage window through
      ethylenediamine-derived functional groups, and the enhanced microporosity of the
      SpectraCarb electrodes for salt adsorption. These results expand the use of i-CDI
      for efficient desalination applications. 

PMID- 26302136
TI  - Fluorodeoxyglucose F(18) Positron Emission Tomography Coupled With Computed
      Tomography in Suspected Acute Renal Allograft Rejection.
AB  - Management of kidney transplant recipients (KTRs) with suspected acute rejection
      (AR) ultimately relies on kidney biopsy; however, noninvasive tests predicting
      nonrejection would help avoid unnecessary biopsy. AR involves recruitment of
      leukocytes avid for fluorodeoxyglucose F(18) ((18) F-FDG), thus (18) F-FDG
      positron emission tomography (PET) coupled with computed tomography (CT) may
      noninvasively distinguish nonrejection from AR. From January 2013 to February
      2015, we prospectively performed 32 (18) F-FDG PET/CT scans in 31 adult KTRs with
      suspected AR who underwent transplant biopsy. Biopsies were categorized into four
      groups: normal (n = 8), borderline (n = 10), AR (n = 8), or other (n = 6,
      including 3 with polyoma BK nephropathy). Estimated GFR was comparable in all
      groups. PET/CT was performed 201 +/- 18 minutes after administration of 3.2 +/-
      0.2 MBq/kg of (18) F-FDG, before any immunosuppression change. Mean standard
      uptake values (SUVs) of both upper and lower renal poles were measured. Mean SUVs
      reached 1.5 +/- 0.2, 1.6 +/- 0.3, 2.9 +/- 0.8, and 2.2 +/- 1.2 for the normal,
      borderline, AR, and other groups, respectively. One-way analysis of variance
      demonstrated a significant difference of mean SUVs among groups. A positive
      correlation between mean SUV and acute composite Banff score was found, with r(2)
      = 0.49. The area under the receiver operating characteristic curve was 0.93,
      with 100% sensitivity and 50% specificity using a mean SUV threshold of 1.6. In
      conclusion, (18) F-FDG PET/CT may help noninvasively prevent avoidable transplant
      biopsies in KTRs with suspected AR. 

PMID- 26302137
TI  - Management of cutaneous squamous cell carcinoma in patients with epidermolysis
      bullosa: best clinical practice guidelines.
AB  - This article summarizes recommendations reached following a systematic literature
      review and expert consensus on the diagnosis and management of cutaneous squamous
      cell carcinomas in people with epidermolysis bullosa. The guidelines are intended
      to help inform decision making by clinicians dealing with this complex
      complication of a devastating disease. 

PMID- 26302138
TI  - Here Today, Gone Tomorrow.

PMID- 26302139
TI  - On 1000-Fold Pharmaceutical Price Markups and Why Drugs Cost More in the United
      States than in Mexico.

PMID- 26302140
TI  - Orchialgia Presenting with Lower Quadrant Pain in Sitting.

PMID- 26302141
TI  - Protective Effect of Regular Physical Activity on Depression After Myocardial
      Infarction: The HUNT Study.
AB  - PURPOSE: To study if physical activity within the recommended level over time was
      associated with risk of developing depression after the first myocardial
      infarction in older adults. METHODS: Men (n = 143) and women (n = 46) who had
      reached the age of 60 years in 2006-2008 who participated in the Nord-Trondelag
      Health Study (HUNT1, 1984-1986; HUNT2, 1995-1997; HUNT3, 2006-2008) without any
      mental illness or cardiovascular disease at baseline in HUNT2 and who experienced
      their first myocardial infarction before HUNT3 were included. Based on the
      patterns of physical activity from HUNT1 to HUNT2, the sample was divided into 4
      groups: persistently inactive, from active to inactive, from inactive to active,
      and persistently active. The primary outcome, post-myocardial infarction
      depression symptoms, was measured with the Hospital, Anxiety and Depression Scale
      in HUNT3. RESULTS: In HUNT3, 11% of participants had depression. After
      multivariable adjustment, those who were persistently active had significantly
      lower odds of being depressed (odds ratio 0.28; 95% confidence interval, 0.08
      0.98) compared with those who were persistently inactive. Additionally, a
      significant test for trend (P = .033) of lowering odds of depression was observed
      across all 4 categories of physical activity patterns at baseline. CONCLUSIONS:
      In this small sample of initially healthy adults, we observed a long-term
      protective effect of regular physical activity on the development of depression
      following myocardial infarction.

PMID- 26302142
TI  - Improving Medication Adherence in Patients with Hypertension: A Randomized Trial.
AB  - BACKGROUND AND PURPOSE: In patients with hypertension, medication adherence is
      often suboptimal, thereby increasing the risk of ischemic heart disease and
      stroke. In a randomized trial, we investigated the effectiveness of a
      multifaceted pharmacist intervention in a hospital setting to improve medication
      adherence in hypertensive patients. Motivational interviewing was a key element
      of the intervention. METHODS: Patients (n = 532) were recruited from 3 hospital
      outpatient clinics and randomized to usual care or a 6-month pharmacist
      intervention comprising collaborative care, medication review, and tailored
      adherence counseling including motivational interviewing and telephone follow
      ups. The primary outcome was composite medication possession ratio (MPR) to
      antihypertensive and lipid-lowering agents, at 1-year follow-up, assessed by
      analyzing pharmacy records. Secondary outcomes at 12 months included persistence
      to medications, blood pressure, hospital admission, and a combined clinical
      endpoint of cardiovascular death, stroke, or acute myocardial infarction.
      RESULTS: At 12 months, 20.3% of the patients in the intervention group (n = 231)
      were nonadherent (MPR <0.80), compared with 30.2% in the control group (n = 285)
      (risk difference -9.8; 95% confidence interval [CI], -17.3, -2.4) and median MPR
      (interquartile range) was 0.93 (0.82-0.99) and 0.91 (0.76-0.98), respectively, P
      = .02. The combined clinical endpoint was reached by 1.3% in the intervention
      group and 3.1% in the control group (relative risk 0.41; 95% CI, 0.11-1.50). No
      significant differences were found for persistence, blood pressure, or hospital
      admission. CONCLUSIONS: A multifaceted pharmacist intervention in a hospital
      setting led to a sustained improvement in medication adherence for patients with
      hypertension. The intervention had no significant impact on blood pressure and
      secondary clinical outcomes.

PMID- 26302143
TI  - Searching for the Source: Bacteremia with Marked Cerebrospinal Fluid Pleocytosis.

PMID- 26302144
TI  - Methamphetamine Cardiotoxicity: Unique Presentation with Multiple Bi-Ventricular
      Thrombi.

PMID- 26302145
TI  - Negative Secular Trends in Medicine: The ABIM Maintenance of Certification and
      Over-reaching Bureaucracy.

PMID- 26302146
TI  - Beyond Body Mass Index: Advantages of Abdominal Measurements for Recognizing
      Cardiometabolic Disorders.
AB  - BACKGROUND: The clinical recognition of cardiometabolic disorders might be
      enhanced by anthropometry based on the sagittal abdominal diameter (SAD; also
      called "abdominal height") or waist circumference rather than on weight. Direct
      comparisons of body mass index (BMI, weight/height(2)) with SAD/height ratio
      (SADHtR) or waist circumference/height ratio (WHtR) have not previously been
      tested in nationally representative populations. METHODS: Nonpregnant adults
      without diagnosed diabetes (ages 20-64 years; n = 3071) provided conventional
      anthropometry and supine SAD (by sliding-beam caliper) in the 2011-2012 US
      National Health and Nutrition Examination Survey. Population-weighted, logistic
      models estimated how strongly each anthropometric indicator was associated with 5
      cardiometabolic disorders: Dysglycemia (glycated hemoglobin >=5.7%), HyperNonHDLc
      (non-high-density-lipoprotein [HDL] cholesterol >=4.14 mmol/L, or taking
      anticholesteremic medications), Hypertension (systolic blood pressure >=140 mm Hg
      or diastolic blood pressure >=90 mm Hg, or taking antihypertensive medications),
      HyperALT (alanine transaminase >=p75 [75th percentile, sex-specific]), and
      HyperGGT (gamma-glutamyltransferase >=p75 [sex-specific]). RESULTS: After scaling
      each indicator, adjusted odds ratios (aORs) tended to be highest for SADHtR and
      lowest for BMI when identifying each disorder except dysglycemia. When SADHtR
      entered models simultaneously with BMI, the aORs for BMI no longer directly
      identified any condition, whereas SADHtR identified persons with HyperNonHDLc by
      aOR 2.78 (95% confidence interval [CI], 1.71-4.51), Hypertension by aOR 2.51 (95%
      CI, 1.22-5.15), HyperALT by aOR 2.89 (95% CI, 1.56-5.37), and HyperGGT by aOR
      5.43 (95% CI, 3.01-9.79). WHtR competed successfully against BMI with regard to
      Dysglycemia, HyperNonHDLc, and HyperGGT. c-Statistics of SADHtR and WHtR were
      higher than those of BMI (P <.001) for identifying HyperNonHDLc and HyperGGT.
      CONCLUSIONS: Among nonelderly adults, SADHtR or WHtR recognized cardiometabolic
      disorders better than did the BMI.

PMID- 26302147
TI  - Highly accelerated chemical exchange saturation transfer (CEST) measurements with
      linear algebraic modeling.
AB  - PURPOSE: In clinical studies, compartmental average chemical exchange saturation
      transfer (CEST) measurements rather than voxel-by-voxel CEST images may suffice
      for evaluating its diagnostic value. A recently developed method-spectroscopy
      with linear algebraic modeling, or SLAM-could directly provide compartmental
      measures with dramatically reduced scan time and optimal signal-to-noise ratios.
      Here, we test whether SLAM can be adapted to significantly accelerate CEST
      acquisitions. THEORY AND METHODS: Conventional anatomical images and raw CEST
      image k-space data were acquired from seven brain tumor patients. SLAM was
      applied to the CEST data using acceleration factors of R = 1-45, after segmenting
      compartments from co-registered images. SLAM-CEST measures were compared with
      average values from the identical compartments obtained by conventional Fourier
      transform (FT) CEST. RESULTS: SLAM generated compartmental average CEST z-spectra
      that were indistinguishable from conventional FT-CEST for R <= 45. SLAM-CEST z
      spectra at +/-3.5 ppm were highly correlated with FT-CEST measures (r(2)  >= 0.98
      for R <= 9; r >= 0.995 for R <= 45). The average error of SLAM-CEST versus FT
      CEST measures was <=10% for R <= 45, in acquisitions requiring as few as a single
      k-space phase-encoding step. CONCLUSION: Applied to patients with brain tumors,
      SLAM-CEST can yield results that are quantitatively equivalent to conventional
      CEST up to 45 times faster, which could prove enabling in clinical settings where
      scan time is limiting. Magn Reson Med 76:136-144, 2016. (c) 2015 Wiley
      Periodicals, Inc.

PMID- 26302148
TI  - Bioinspired Underwater Superoleophobic Membrane Based on a Graphene Oxide Coated
      Wire Mesh for Efficient Oil/Water Separation.
AB  - Inspired from fish scales that exhibit unique underwater superoleophobicity
      because of the presence of micronanostructures and hydrophilic slime on their
      surface, we reported here the facile fabrication of underwater superoleophobic
      membranes by coating a layer of graphene oxide (GO) on commercially available
      wire meshes with tunable pore sizes. Using the wire mesh as a ready-made mask, GO
      embellished mesh with open apertures (GO@mesh) could be readily fabricated after
      subsequent O2 plasma treatments from the back side. Interestingly, the congenital
      microstructures of the crossed microwires in combination with the abundant
      hydrophilic oxygen-containing groups of the GO layer endow the resultant GO@mesh
      with unique underwater superoleophobic properties. The antioil tests show that
      the underwater contact angles of various oils including both organic reagents
      (undissolved in water) and vegetable oil on GO@mesh exceed 150 degrees ,
      indicating the superoleophobic nature. In a representative experiment, a mixture
      of bean oil and water that imitates culinary sewage has been well separated with
      the help of our GO@mesh. GO-embellished wire meshes may find broad applications
      in sewage purification, especially for the treatment of oil contaminations. 

PMID- 26302149
TI  - A Bayesian model for quantifying the change in mortality associated with future
      ozone exposures under climate change.
AB  - Climate change is expected to have many impacts on the environment, including
      changes in ozone concentrations at the surface level. A key public health concern
      is the potential increase in ozone-related summertime mortality if surface ozone
      concentrations rise in response to climate change. Although ozone formation
      depends partly on summertime weather, which exhibits considerable inter-annual
      variability, previous health impact studies have not incorporated the variability
      of ozone into their prediction models. A major source of uncertainty in the
      health impacts is the variability of the modeled ozone concentrations. We propose
      a Bayesian model and Monte Carlo estimation method for quantifying health effects
      of future ozone. An advantage of this approach is that we include the uncertainty
      in both the health effect association and the modeled ozone concentrations. Using
      our proposed approach, we quantify the expected change in ozone-related
      summertime mortality in the contiguous United States between 2000 and 2050 under
      a changing climate. The mortality estimates show regional patterns in the
      expected degree of impact. We also illustrate the results when using a common
      technique in previous work that averages ozone to reduce the size of the data,
      and contrast these findings with our own. Our analysis yields more realistic
      inferences, providing clearer interpretation for decision making regarding the
      impacts of climate change. 

PMID- 26302151
TI  - Complementary and Alternative Medicine Use in Pediatric Hematology/Oncology
      Patients at the University of Mississippi Medical Center.
AB  - OBJECTIVE: To examine the prevalence and modalities of complementary and
      alternative medicine (CAM) use in children with cancer and sickle cell disease;
      the reasons for use of CAM; and the use of CAM before, during, and after
      treatment in children with cancer. METHODS: This single-center, observational
      study administered caregivers a written questionnaire regarding the use of CAM
      therapies. RESULTS: A total of 101 caregivers completed questionnaires. Including
      prayer, total CAM use in oncology and sickle cell disease was 64% and 63%,
      respectively. Non-prayer CAM use was 30% in oncology and 23% in sickle cell
      disease. Of respondents who reported using any CAM, the three most commonly used
      types were prayer (62.3% oncology; 60.0% sickle cell disease), vitamins/minerals
      (14.8% oncology; 10.0% sickle cell disease), and massage (9.8% oncology; 7.5%
      sickle cell disease). The primary reasons for using CAM were to provide hope, to
      improve quality of life, and to lessen adverse effects. In oncology patients, CAM
      use tended to increase during treatment compared with before and after treatment.
      CONCLUSIONS: The reported prevalence of non-prayer CAM use was lower (23%-30%) in
      this sample than has been reported in national samples or other geographic
      regions of the United States. Nonetheless, participants reported many positive
      reasons for using CAM, including to gain hope, improve quality of life, and
      control pain. Thus, CAM use appears to be an important aspect of medical care for
      many pediatric hematology/oncology families and should be a consideration when
      providers are discussing treatment and quality of care with families.

PMID- 26302152
TI  - Bridging Unmet Medical Device Ecosystem Needs With Strategically Coordinated
      Registries Networks.

PMID- 26302150
TI  - Sustained Isoprostane E2 Elevation, Inflammation and Fibrosis after Acute
      Ischaemia-Reperfusion Injury Are Reduced by Pregnane X Receptor Activation.
AB  - Liver grafts donated after cardiac death are increasingly used to expand the
      donor pool but are prone to ischaemic-type biliary lesions. The anti-inflammatory
      effects of the activated pregnane X receptor have previously been shown to be
      beneficial in a number of inflammatory liver conditions. However, its role in
      reducing peri-portal inflammation and fibrosis following ischaemia-reperfusion
      injury has not been investigated. Hepatic injury and its response to pregnane X
      receptor activation was examined after partial hepatic ischaemia-reperfusion
      injury induced by surgically clamping the left and middle lobar blood vessels in
      rats. Molecular and pathological changes in the liver were examined over the
      following 28 days. Ischaemia-reperfusion injury resulted in transient cholestasis
      associated with microvillar changes in biliary epithelial cell membranes and
      hepatocellular injury which resolved within days after reperfusion. However, in
      contrast to chemically-induced acute liver injuries, this was followed by
      sustained elevation in isoprostane E2, peri-portal inflammation and fibrosis that
      remained unresolved in the ischaemic reperfused lobe for at least 28 days after
      clamping. Administration of pregnenolone-16alpha-carbonitrile--a rodent-specific
      pregnane X receptor activator--resulted in significant reductions in cholestasis,
      hepatic injury, ischaemic lobe isoprostane E2 levels, peri-portal inflammation
      and fibrosis. Hepatic ischaemia-reperfusion injury therefore results in
      inflammatory and fibrotic changes that persist well beyond the initial ischaemic
      insult. Drug-mediated activation of the pregnane X receptor reduced these adverse
      changes in rats, suggesting that the pregnane X receptor is a viable drug target
      to reduce ischaemic-type biliary lesions in recipients of liver transplants
      donated after cardiac death.

PMID- 26302154
TI  - Slippery Wenzel State.
AB  - Enhancing the mobility of liquid droplets on rough surfaces is of great interest
      in industry, with applications ranging from condensation heat transfer to water
      harvesting to the prevention of icing and frosting. The mobility of a liquid
      droplet on a rough solid surface has long been associated with its wetting state.
      When liquid drops are sitting on the top of the solid textures and air is trapped
      underneath, they are in the Cassie state. When the drops impregnate the solid
      textures, they are in the Wenzel state. While the Cassie state has long been
      associated with high droplet mobility and the Wenzel state with droplet pinning,
      our work challenges this existing convention by showing that both Cassie and
      Wenzel state droplets can be highly mobile on nanotexture-enabled slippery rough
      surfaces. Our surfaces were developed by engineering hierachical nano- and
      microscale textures and infusing liquid lubricant into the nanotextures alone to
      create a highly slippery rough surface. We have shown that droplet mobility can
      be maintained even after the Cassie-to-Wenzel transition. Moreover, the discovery
      of the slippery Wenzel state allows us to assess the fundamental limits of the
      classical and recent Wenzel models at the highest experimental precision to date,
      which could not be achieved by any other conventional rough surface. Our results
      show that the classical Wenzel eq (1936) cannot predict the wetting behaviors of
      highly wetting liquids in the Wenzel state. 

PMID- 26302153
TI  - Deletion of Kinin B2 Receptor Alters Muscle Metabolism and Exercise Performance.
AB  - Metabolic syndrome is a cluster of metabolic risk factors such as obesity,
      diabetes and cardiovascular diseases. Mitochondria is the main site of ATP
      production and its dysfunction leads to decreased oxidative phosphorylation,
      resulting in lipid accumulation and insulin resistance. Our group has
      demonstrated that kinins can modulate glucose and lipid metabolism as well as
      skeletal muscle mass. By using B2 receptor knockout mice (B2R-/-) we investigated
      whether kinin action affects weight gain and physical performance of the animals.
      Our results show that B2R-/- mice are resistant to high fat diet-induced obesity,
      have higher glucose tolerance as well as increased mitochondrial mass. These
      features are accompanied by higher energy expenditure and a lower feed efficiency
      associated with an increase in the proportion of type I fibers and intermediary
      fibers characterized by higher mitochondrial content and increased expression of
      genes related to oxidative metabolism. Additionally, the increased percentage of
      oxidative skeletal muscle fibers and mitochondrial apparatus in B2R-/- mice is
      coupled with a higher aerobic exercise performance. Taken together, our data give
      support to the involvement of kinins in skeletal muscle fiber type distribution
      and muscle metabolism, which ultimately protects against fat-induced obesity and
      improves aerobic exercise performance. 

PMID- 26302156
TI  - The Cervical Osteology of Okapia johnstoni and Giraffa camelopardalis.
AB  - Giraffidae is the only family of ruminants that is represented by two extant
      species; Okapia johnstoni and Giraffa camelopardalis. Of these taxa, O. johnstoni
      represents a typical short-necked ungulate, and G. camelopardalis exemplifies the
      most extreme cervical elongation seen in any ruminant. We utilize these two
      species to provide a comprehensive anatomic description of the cervical
      vertebrae. In addition, we compare the serial morphologic characteristics of the
      okapi and giraffe cervical vertebrae, and report on several osteologic
      differences seen between the two taxa. The giraffe neck appears to exhibit
      homogenization of C3-C7; the position of the dorsal tubercle, thickness of the
      cranial articular process, shape of the ventral vertebral body, and orientation
      of the ventral tubercle are constant throughout these vertebrae, whereas these
      features are serially variable in the okapi. We also report on several
      specializations of the giraffe C7, which we believe relates to an atypical
      cervico-thoracic junction, corresponding to the substantial neck lengthening. The
      morphologic differences exhibited between the okapi and giraffe cervical
      vertebrae have implications on the function of the necks relating to both
      fighting and feeding. 

PMID- 26302155
TI  - Antibody-Coupled Magnetic Beads Can Be Reused in Immuno-MRM Assays To Reduce Cost
      and Extend Antibody Supply.
AB  - Immunoaffinity enrichment of peptides coupled to targeted, multiple reaction
      monitoring mass spectrometry (immuno-MRM) enables precise quantification of
      peptides. Affinity-purified polyclonal antibodies are routinely used as affinity
      reagents in immuno-MRM assays, but they are not renewable, limiting the number of
      experiments that can be performed. In this technical note, we describe a workflow
      to regenerate anti-peptide polyclonal antibodies coupled to magnetic beads for
      enrichments in multiplex immuno-MRM assays. A multiplexed panel of 44 antibodies
      (targeting 60 peptides) is used to show that peptide analytes can be effectively
      stripped off of antibodies using acid washing without compromising assay
      performance. The performance of the multiplexed panel (determined by correlation,
      agreement, and precision of reused assays) is reproducible (R(2) between 0.81 and
      0.99) and consistent (median CVs 8-15%) for at least 10 times of washing and
      reuse. Application of this workflow to immuno-MRM studies greatly reduces per
      sample assay cost and increases the number of samples that can be interrogated
      with a limited supply of polyclonal antibody reagent. This allows more
      characterization for promising and desirable targets prior to committing funds
      and efforts to conversion to a renewable monoclonal antibody. 

PMID- 26302157
TI  - Phosphinoalkylidene and -alkylidyne Complexes of Titanium: Intermolecular C-H
      Bond Activation and Dehydrogenation Reactions.
AB  - The ethylene complex (PNP)Ti(eta(2)-H2C?CH2)(CH2(t)Bu) or
      (PNP)Ti?CH(t)Bu(CH2(t)Bu) (PNP(-) = N[2-P(CHMe2)2-4-methylphenyl]2) reacts with
      H2CPPh3 to form the kappa(2)-phosphinoalkylidene (PNP)Ti?CHPPh2(Ph) (1). Compound
      1 activates benzene via the transient intermediate [(PNP)Ti=CPPh2] (C). By
      treatment of (PNP)Ti?CH(t)Bu(OTf) with LiCH2PPh2, 1 or its isotopologue
      (PNP)Ti?CDPPh2(C6D5) (1-d6) can be produced by an independent route involving
      intermediate C, which activates benzene or benzene-d6 and dehydrogenates
      cyclohexane-d12. Addition of MeOTf to 1 results in elimination of benzene
      concomitant with the formation of the phosphonioalkylidyne complex,
      [(PNP)Ti=CPPh2Me(OTf) (2). Theoretical studies of 2 suggest a resonance structure
      having dominant Ti-C triple-bond character with some contribution also from a C-P
      multiple bond. 

PMID- 26302158
TI  - Learning to live without the cerebellum.
AB  - The near-total absence of the cerebellum is a rare congenital condition with a
      wide phenotypic heterogeneity ranging from a severe to mild impairment of motor,
      cognitive, and behavioral functions. In this study, the case of a 48-year-old
      right-handed man with a near-total absence of the cerebellum was examined with
      the aim of understanding the long-term reorganization of a brain developed
      without a cerebellum. Clinical, neuropsychological evaluation and a neuroimaging
      study on a 3-T scanner were carried out. Both conventional structural diffusion
      tensor imaging (DTI) and functional (resting-state fMRI) data were acquired. A
      severe neuropsychomotor delay in infancy and adolescence involving motor skills,
      cognitive, and affective competencies was observed, which improved over the
      years. Conventional MRI findings confirmed the complete absence of the
      cerebellum. Analysis of DTI and resting-state fMRI data showed an impairment of
      the executive-control network, involving areas strongly connected with the
      cerebellum through the frontopontine fibers. The neuroimaging findings excluded
      the involvement of the extracerebellar structure. In conclusion, our data support
      the vascular genesis hypothesis for this rare pathology, consistent with an
      acquired embryonic cerebellar insult. This case also shows that it is possible to
      learn to live without the cerebellum over time. 

PMID- 26302159
TI  - The transient decline in hippocampal theta power during response inhibition in a
      positive patterning task.
AB  - It is believed that a transient decline in hippocampal theta power is induced by
      behavioral inhibition during a go/no-go stimulus discrimination task. In a
      previously reported positive patterning (PP) task, rats learn to lever press when
      a compound stimulus, both tone and light, is presented and inhibit their lever
      press when a single stimulus, tone or light, is presented. In this task, rats
      were required to inhibit their response to the single stimulus in a task where
      both compound and single stimuli were presented with an overlapping element.
      Thus, we hypothesized that there would be a transient decline in hippocampal
      theta power induced by behavioral inhibition to the presence of a single stimuli
      in the PP task. The result of this study showed that a decline in hippocampal
      theta power occurred during response inhibition to the presence of a single tone
      stimulus in the PP task, supporting our hypothesis. However, we did not observe
      any decline in hippocampal theta power during response inhibition to the presence
      of a single light stimulus. We found that the error response rate for the tone
      stimulus was slightly lower than that for light stimulus in the PP task. Thus, we
      proposed that the decline in hippocampal theta power related to more accurate
      response inhibition to the stimulus that had an overlapping element. 

PMID- 26302160
TI  - Changes in transient receptor potential channels in the rat geniculate ganglion
      after chorda tympani nerve injury.
AB  - We reported differential expression of the transient receptor potential vanilloid
      1 (TRPV1), the transient receptor potential ankyrin 1 (TRPA1), and the (TRPM8) in
      the geniculate ganglions (GGs) of naive rats. In medical practice, the chorda
      tympani nerve (CTN) is injured in some patients during middle-ear surgery, and
      results in tongue numbness and taste disorder. We investigated changes in the
      expression of these receptors in GGs after CTN injury. In naive-rat GGs, 11.4,
      11.8, and 0.5% of neurons were found to express the TRPV1, the TRPA1, the TRPM8,
      respectively. At 3 days after CTN injury, 5.2 and 4.0% of activating
      transcription factor 3-immunoreactive neurons, considered as injured neurons,
      were found to express the TRPV1 and the TRPA1, respectively. Among activating
      transcription factor 3-immunonegative neurons, considered as uninjured neurons,
      3.9 and 3.8% were found to express the TRPV1 and the TRPA1, respectively. The
      TRPM8 was not detected in GGs after CTN injury. We found decreased mRNA levels of
      the TRPV1 and the TRPA1 in all neurons, as well as in uninjured neurons of
      ipsilateral GGs after CTN injury. CTN injury changes the gene expression in GGs
      and may have effects on the tongue. 

PMID- 26302161
TI  - Inhibition of p53 attenuates ischemic stress-induced activation of astrocytes.
AB  - In cerebral ischemia, studies of cell death have focused primarily on neurons,
      but recent work indicates that ischemia also causes damage to astrocytes.
      Activation of astrocytes is a typical brain response to stress stimuli and is
      evidenced by changes in cellular function and morphology, as well as upregulation
      of glial fibrillary acidic protein. The tumor-suppressor transcription factor p53
      has recently been implicated as a mediator of ischemia-induced neuronal death,
      but very little is known about its role in the activation or the death of
      astrocytes. The present study investigated the role of p53 in astrocyte and
      neuronal toxicity using in-vitro and in-vivo ischemic stroke models. We showed
      that p53 is activated in ischemic brains and in oxygen-glucose deprivation (OGD)
      induced cell death in neurons and astrocytes. Inhibition of p53 activity using
      either pifithrin-alpha or small interference RNA interference reduced OGD-induced
      cell death and pifithrin-alpha reversed OGD-induced impairment of glutamate
      uptake in astrocytes, suggesting that p53 might play a key role in mediating
      neurotoxicity and gliotoxicity in ischemic brain injury. This study shows that
      p53 is activated in astrocytes during ischemia and that inhibition of the
      activity of this molecule prevents not only OGD-induced neuronal and astrocytic
      death but also astrocyte activation and impaired glutamate uptake. These findings
      suggest that p53 may be a valuable therapeutic target in ischemic brain injury. 

PMID- 26302162
TI  - Ontogenic expression profiles and oxaliplatin regulation of leptin expression in
      mice dorsal root ganglion.
AB  - Leptin is widely distributed in many tissues, including the nervous system.
      However, the ontogeny of leptin expression in the dorsal root ganglion (DRG) is
      unclear. Recent studies have shown that leptin is involved in the regulation of
      neuropathic pain induced by nerve injury. Our previous results showed that
      exogenous leptin administration alleviated the pain behaviors induced by chronic
      constriction sciatic nerve injury. In the present study, the ontogenic expression
      of leptin was detected in the DRG of the mouse embryo at days 15.5 (E15.5),
      E17.5, and E19.5 of gestation and in the postnatal mouse at days 5 (P5), P15, and
      P25, and in the adult mouse. Leptin immunoreactivity and mRNA were not found in
      DRG at E15.5. The percentage of leptin immunopositive (leptin) neurons was about
      27% at E17.5. It continued to increase to about 70% at P5. From P5 to P15, there
      was no significant change. The proportion of DRG neurons positive for leptin
      decreased after P15 and there were about 41% leptin neurons in adults. The
      expression profile of leptin mRNA is similar to leptin immunoreactivity.
      Oxaliplatin (OXA) is an effective platinum-based drug used as first-line
      chemotherapy for advanced colorectal cancer. However, it may induce neuropathic
      pain. In the current study, we found that the expression of leptin was increased
      in the lumbar 4-6 DRG of OXA-treated mice. These results indicate that leptin is
      involved in the regulation of DRG development and OXA-induced neuropathic pain. 

PMID- 26302163
TI  - Possible involvement of the cerebellum in motor-function impairment in
      progranulin-deficient mice.
AB  - Progranulin (PGRN) is a multifunctional growth factor involved in many
      physiological and pathological processes in the brain such as sexual
      differentiation, neurogenesis, neuroinflammation, and neurodegeneration.
      Previously, we showed that PGRN was expressed broadly in the brain and the
      Purkinje cells in the cerebellum were one of the regions with the highest
      expression level of PGRN. Thus, in the present study, we investigated the
      possible roles of PGRN in the cerebellum by comparing wild-type (WT) and PGRN
      deficient (KO) mice with immunohistochemical staining for calbindin, a marker of
      Purkinje cells. The results showed that the density of Purkinje cell dendrites in
      the molecular layer of the cerebellum was significantly higher in KO mice than in
      WT mice, although the number of cell bodies was comparable between the genotypes.
      Subsequently, as the cerebellum is the center of the motor function, we performed
      a rotarod test and found that KO mice remained on the rotating rod for
      significantly shorter periods than WT mice. However, KO and WT mice did not
      differ significantly with respect to the diameter of myofibers in a skeletal
      muscle. These results suggest that PGRN is involved in the development and/or
      maturation of neuronal networks comprising Purkinje cells in the cerebellum,
      which may be a prerequisite to normal motor function. 

PMID- 26302164
TI  - Swine Influenza Virus and Association with the Porcine Respiratory Disease
      Complex in Pig Farms in Southern Brazil.
AB  - Despite the putative endemic status of swine influenza A virus (swIAV)
      infections, data on the occurrence of swine influenza outbreaks are scarce in
      Brazil. The aim of this study was to detect and subtype swIAVs from six outbreaks
      of porcine respiratory disease complex (PRDC) in southern Brazil. Nasal swabs
      were collected from 66 piglets with signs of respiratory disease in six herds.
      Lung tissue samples were collected from six necropsied animals. Virus detection
      was performed by PCR screening and confirmed by virus isolation and
      hemagglutination (HA). Influenza A subtyping was performed by a real-time reverse
      transcriptase PCR (rRT-PCR) to detect the A(H1N1)pdm09; other swIAV subtypes were
      determined by multiplex RT-PCR. In lung tissues, the major bacterial and viral
      pathogens associated with PRDC (Pasteurella multocida, Mycoplasma hyopneumoniae,
      Actinobacillus pleuropneumoniae, Haemophilus parasuis and PCV2) were
      investigated. In some affected pigs, clinico-pathological evaluations were
      conducted. Influenza A was detected by screening PCR in 46 of 66 swab samples and
      from five of six lungs. Virus was recovered from pigs of all six herds. Subtype
      A(H1N1)pdm09 was detected in four of six herds and H1N2 in the other two herds.
      In lung tissues, further agents involved in PRDC were detected in all cases;
      Pasteurella multocida was identified in five of six samples and Mycoplasma
      hyopneumoniae in three of six. Actinobacillus pleuropneumoniae (1/6), Haemophilus
      parasuis (1/6) and PCV2 (1/6) were also detected. These findings indicate that
      subtypes A(H1N1)pdm09 and H1N2 were present in pigs in southern Brazil and were
      associated with PRDC outbreaks. 

PMID- 26302165
TI  - The response modulation hypothesis of psychopathy: A meta-analytic and narrative
      analysis.
AB  - The causes of psychopathy, a condition characterized by interpersonal (e.g.,
      superficial charm), affective (e.g., lack of empathy), and behavioral (e.g.,
      impulsive actions) features, remain contested. The present review examines 1 of
      the most influential etiological models of psychopathy, the response modulation
      hypothesis (RMH), which proposes that psychopathic individuals exhibit
      difficulties in adjusting their behavior in the presence of a dominant response
      set. We conduct a meta-analysis and narrative literature review to examine the
      RMH quantitatively and qualitatively, estimate the statistical effects of
      response modulation (RM) deficits in psychopathic individuals, and ascertain the
      boundary conditions of the RMH. Ninety-four samples from published and
      unpublished studies involving 7,340 participants were identified for inclusion.
      Overall results provided some support for the RMH, revealing a small to medium
      relationship between psychopathy and RM deficits (r = .20, p < .001, d = .41)
      that extended to both psychopathy dimensions. Moreover, as predicted by the RMH,
      RM deficits were observed for both affectively neutral and affectively laden
      tasks. A number of moderators, such as anxiety, laboratory task, dependent
      measure, psychopathy measure, and race, contributed to significant variability in
      effect sizes; we also found evidence for potential publication bias using 2
      methods, raising questions concerning the robustness of RM findings. An ancillary
      narrative review revealed that the RMH is inconsistent with a number of
      replicated findings in the psychopathy literature, suggesting that the RMH, at
      least in its present form, is unlikely to provide a comprehensive etiological
      account of psychopathy. Nevertheless, more recent attentional versions of the RMH
      may hold promise with respect to intervention. Further fruitful directions for
      research on the RMH, including the use of multiple dependent measures of RM and
      latent variable approaches, are delineated.

PMID- 26302166
TI  - Lack of association of rs3798220 with small apolipoprotein(a) isoforms and high
      lipoprotein(a) levels in East and Southeast Asians.
AB  - OBJECTIVE: The variant allele of rs3798220 in the apolipoprotein(a) gene (LPA) is
      used to assess the risk for coronary artery disease (CAD) in Europeans, where it
      is associated with short alleles of the Kringle IV-2 (KIV-2) copy number
      variation (CNV) and high lipoprotein(a) (Lp(a)) concentrations. No association of
      rs3798220 with CAD was detected in a GWAS of East Asians. Our study investigated
      the association of rs3798220 with Lp(a) concentrations and KIV-2 CNV size in non
      European populations to explain the missing association of the variant with CAD
      in Asians. METHODS: We screened three populations from Africa and seven from Asia
      by TaqMan Assay for rs3798220 and determined KIV-2 CNV sizes of LPA alleles by
      pulsed-field gel electrophoresis (PFGE). Additionally, CAD cases from India were
      analysed. To investigate the phylogenetic origin of rs3798220, 40 LPA alleles
      from Chinese individuals were separated by PFGE and haplotyped for further SNPs.
      RESULTS: The variant was not found in Africans. Allele frequencies in East and
      Southeast Asians ranged from 2.9% to 11.6%, and were very low (0.15%) in CAD
      cases and controls from India. The variant was neither associated with short KIV
      2 CNV alleles nor elevated Lp(a) concentrations in Asians. CONCLUSION: Our study
      shows that rs3798220 is no marker for short KIV-2 CNV alleles and high Lp(a) in
      East and Southeast Asians, although the haplotype background is shared with
      Europeans. It appears unlikely that this SNP confers atherogenic potential on its
      own. Furthermore, this SNP does not explain Lp(a) attributed risk for CAD in
      Asian Indians.

PMID- 26302168
TI  - The association between plasma matrix metalloproteinase-9 concentration and
      endoleak after endovascular aortic aneurysm repair: a meta-analysis.
AB  - BACKGROUND: The most common complication after endovascular aneurysm repair
      (EVAR) is continued perfusion of the aneurysmal sac, known as endoleak.
      Assessment of markers released from the aneurysm wall into the circulation has
      been suggested as a possible alternative for detecting endoleaks. The aim of this
      meta-analysis was to examine if circulating concentrations of matrix
      metalloproteinase (MMP)-9 were higher in patients with endoleak after EVAR.
      METHODS: A systematic search of the MEDLINE, EMBASE, Scopus, Web of Science and
      Cochrane Library Databases was conducted. Studies reporting circulating MMP-9
      concentrations in patients who did and did not have endoleaks after EVAR that met
      inclusion and exclusion criteria were included. A meta-analysis using a random
      effects model was performed to assess the association between circulating
      concentrations of MMP-9 and endoleak. Sensitivity analyses were performed using
      the one-study remove approach. Study quality was assessed using a quality
      assessment tool. RESULTS: Prior to EVAR, plasma concentrations of MMP-9 were
      similar in patients that did and did not subsequently develop an endoleak
      (Standardised mean difference: -0.13; 95% confidence interval, -0.63 to 0.37,
      p=0.60). 1 month after EVAR, plasma concentrations of MMP-9 were non
      significantly higher in patients that had an endoleak (Standardized mean
      difference: 0.56; 95% CI -0.02 to 1.15, p=0.06). 3 months after EVAR, plasma
      concentrations of MMP-9 were higher in patients that had an endoleak
      (Standardised mean difference: 1.42; 95% confidence interval, 0.48-2.36,
      p<0.003). CONCLUSIONS: This meta-analysis suggests that plasma MMP-9
      concentrations measured 3 months after EVAR are higher in patients that have an
      endoleak. It remains to be established whether plasma MMP-9 testing is
      sufficiently accurate for use as a surveillance test for endoleak after EVAR.

PMID- 26302169
TI  - More than meets the eye: from carotenoid biosynthesis, to new insights into
      apocarotenoid signaling.
AB  - Carotenoids are a class of isoprenoids synthesized almost exclusively in plants
      involved in a myriad of roles including the provision of flower and fruit
      pigmentation for the attraction of pollinators and seed dispersing organisms.
      While carotenoids are essential throughout plant development, they are also
      extremely important in human diets providing necessary nutrition and aiding in
      the prevention of various cancers, age-related diseases and macular degeneration.
      Utilization of multiple plant models systems (i.e. Arabidopsis; maize; and
      tomato) has provided a comprehensive framework detailing the regulation of
      carotenogenesis throughout plant development covering all levels of genetic
      regulation from epigenetic to post-translational modifications. That said, the
      understanding of how carotenoids self-regulate remains fragmented. Recent reports
      demonstrate the potential influence of carotenoid-cleavage products
      (apocarotenoids) as signaling molecules regulating carotenoid biosynthesis in
      addition to various aspects of plants development (i.e. leaf and root
      development). This review highlights recent advances in carotenogenic regulation
      and insights into potential roles of novel apocarotenoids in plants. 

PMID- 26302167
TI  - Association of relative telomere length with cardiovascular disease in a large
      chronic kidney disease cohort: the GCKD study.
AB  - BACKGROUND: Chronic kidney disease (CKD) affects 10-15% of the general population
      and affected individuals are at an increased risk for cardiovascular disease
      (CVD). Since telomere length is considered to be involved in biological aging, we
      tested whether relative telomere length (RTL) might be a marker for these two
      diseases. METHODS: The German Chronic Kidney Disease (GCKD) study is an ongoing
      prospective cohort study including patients with CKD of moderate severity. RTL
      was measured by qPCR in 4955 out of 5217 GCKD patients at baseline. RESULTS: RTL
      was distributed in the cohort with a mean +/- SD of 0.95 +/- 0.19. CVD was
      present in 1266 patients. Each decrease of RTL by 0.1 unit was associated with a
      higher probability for prevalent CVD: OR = 1.06, 95% CI 1.02-1.11, p = 0.007
      (adjusted for age, sex, eGFR, BMI, ln-CRP, smoking, hypertension, diabetes, and
      lipids). Similar findings were observed for history of specific CVD entities,
      such as coronary artery disease (OR = 1.05, p = 0.025), myocardial infarction (OR
      = 1.08, p = 0.013) and percutaneous transluminal coronary angioplasty (OR = 1.06,
      p = 0.032). The strongest associations were found for interventions at the
      carotid arteries (OR = 1.25, p = 0.001) as well as aortic aneurysms (OR = 1.22, p
      = 0.001). CONCLUSIONS: In the presence of CKD there is a significant association
      between shorter RTL and CVD manifestations. RTL appears to be a marker reflecting
      changes in homeostasis associated with CKD that may contribute to the excess CVD
      risk.

PMID- 26302171
TI  - NMR Spectroscopy Identifies Metabolites Translocated from Powdery Mildew
      Resistant Rootstocks to Susceptible Watermelon Scions.
AB  - Powdery mildew (PM) disease causes significant loss in watermelon. Due to the
      unavailability of a commercial watermelon variety that is resistant to PM,
      grafting susceptible cultivars on wild resistant rootstocks is being explored as
      a short-term management strategy to combat this disease. Nuclear magnetic
      resonance-based metabolic profiles of susceptible and resistant rootstocks of
      watermelon and their corresponding susceptible scions (Mickey Lee) were compared
      to screen for potential metabolites related to PM resistance using multivariate
      principal component analysis. Significant score plot differences between the
      susceptible and resistant groups were revealed through Mahalanobis distance
      analysis. Significantly different spectral buckets and their corresponding
      metabolites (including choline, fumarate, 5-hydroxyindole-3-acetate, and
      melatonin) have been identified quantitatively using multivariate loading plots
      and verified by volcano plot analyses. The data suggest that these metabolites
      were translocated from the powdery mildew resistant rootstocks to their
      corresponding powdery mildew susceptible scions and can be related to PM disease
      resistance. 

PMID- 26302170
TI  - Trichodysplasia spinulosa-Associated Polyomavirus Uses a Displaced Binding Site
      on VP1 to Engage Sialylated Glycolipids.
AB  - Trichodysplasia spinulosa-associated Polyomavirus (TSPyV) was isolated from a
      patient suffering from trichodysplasia spinulosa, a skin disease that can appear
      in severely immunocompromised patients. While TSPyV is one of the five members of
      the polyomavirus family that are directly linked to a human disease, details
      about molecular recognition events, the viral entry pathway, and intracellular
      trafficking events during TSPyV infection remain unknown. Here we have used a
      structure-function approach to shed light on the first steps of TSPyV infection.
      We established by cell binding and pseudovirus infection studies that TSPyV
      interacts with sialic acids during attachment and/or entry. Subsequently, we
      solved high-resolution X-ray structures of the major capsid protein VP1 of TSPyV
      in complex with three different glycans, the branched GM1 glycan, and the linear
      trisaccharides alpha2,3- and alpha2,6-sialyllactose. The terminal sialic acid of
      all three glycans is engaged in a unique binding site on TSPyV VP1, which is
      positioned about 18 A from established sialic acid binding sites of other
      polyomaviruses. Structure-based mutagenesis of sialic acid-binding residues leads
      to reduction in cell attachment and pseudovirus infection, demonstrating the
      physiological relevance of the TSPyV VP1-glycan interaction. Furthermore,
      treatments of cells with inhibitors of N-, O-linked glycosylation, and
      glycosphingolipid synthesis suggest that glycolipids play an important role
      during TSPyV infection. Our findings elucidate the first molecular recognition
      events of cellular infection with TSPyV and demonstrate that receptor recognition
      by polyomaviruses is highly variable not only in interactions with sialic acid
      itself, but also in the location of the binding site. 

PMID- 26302173
TI  - Effect of Sterical Shielding on the Redox Properties of Imidazoline and
      Imidazolidine Nitroxides.
AB  - The oxidant properties of the series of 2,2,5,5-tetraalkyl imidazoline and
      imidazolidine nitroxides were investigated. An increase in the number of bulky
      alkyl substituents leads to a decrease in the rate of reduction with ascorbate,
      which makes the electrochemical reduction potential more negative and shifts the
      equilibrium in the mixture of nitroxide and reference hydroxylamine (3-carboxy-1
      hydroxy-2,2,5,5-tetramethylpyrrolidine-1-oxyl-1-(15)N) toward the starting
      compounds. The effect of structural factors on these reactions was analyzed by
      means of multiple regression using the Fujita steric constant Es and the
      inductive Hammett constant sigmaI. Satisfactory statistical outputs were obtained
      in all of the biparameter correlations, denoting that the oxidant properties of
      the nitroxides are determined by steric and electronic effects of the
      substituents. The data imply that bulky substituents can stabilize nitroxide
      and/or destabilize hydroxylamine. 

PMID- 26302172
TI  - A highly selective mitochondria-targeting fluorescent K(+) sensor.
AB  - Regulation of intracellular potassium (K(+) ) concentration plays a key role in
      metabolic processes. So far, only a few intracellular K(+) sensors have been
      developed. The highly selective fluorescent K(+) sensor KS6 for monitoring K(+)
      ion dynamics in mitochondria was produced by coupling triphenylphosphonium,
      borondipyrromethene (BODIPY), and triazacryptand (TAC). KS6 shows a good response
      to K(+) in the range 30-500 mM, a large dynamic range (Fmax /F0 ~130), high
      brightness (phif =14.4 % at 150 mM of K(+) ), and insensitivity to both pH in the
      range 5.5-9.0 and other metal ions under physiological conditions. Colocalization
      tests of KS6 with MitoTracker Green confirmed its predominant localization in the
      mitochondria of HeLa and U87MG cells. K(+) efflux/influx in the mitochondria was
      observed upon stimulation with ionophores, nigericin, or ionomycin. KS6 is thus a
      highly selective semiquantitative K(+) sensor suitable for the study of
      mitochondrial potassium flux in live cells. 

PMID- 26302174
TI  - Improved detection by ensemble-decision aliquot ranking of circulating tumor
      cells with low numbers of a targeted surface antigen.
AB  - Circulating tumor cells (CTCs) are shed from a solid tumor into the bloodstream
      and can seed new metastases. CTCs hold promise for cancer diagnosis and prognosis
      and to increase our understanding of the metastatic process. However, their low
      numbers in blood and varied phenotypic characteristics make their detection and
      isolation difficult. One source of heterogeneity among CTCs is molecular: When
      they leave the primary tumor, these cells must undergo a molecular transition,
      which increases their mobility and chance of survival in the blood. During this
      molecular transition, the cells lose some of their epithelial character, which is
      manifested by the expression of the cell surface antigen known as epithelial cell
      adhesion molecule (EpCAM). Some tumors shed CTCs that express high levels of
      EpCAM; others release cells that have a low level of the antigen. Nevertheless,
      many CTC isolation techniques rely on the detection of EpCAM to discriminate CTCs
      from other cells in the blood. We previously reported a high-throughput
      immunofluorescence-based technology that targets EpCAM to rank aliquots of blood
      for the presence or absence of a CTC. This technology, termed ensemble decision
      aliquot ranking (eDAR), recovered spiked-in cancer cells (taken from a model
      EpCAM(high) cell line) from blood at an efficiency of 95%. In this paper, we
      evaluated eDAR for recovery of cells that have low EpCAM expression and developed
      an immunofluorescence labeling strategy that significantly enhances the method's
      performance. Specifically, we used a cocktail of primary antibodies for both
      epithelial and mesenchymal antigens as well as a dye-linked secondary antibody.
      The cocktail allowed us to reliably detect a model EpCAM(low) cell line for
      triple negative breast cancer, MDA-MB-231, with a recovery efficiency of 86%.
      Most significantly, we observed an average of 6-fold increase in the number of
      CTCs isolated from blood samples from breast cancer patients. These findings
      underscore the importance of benchmarking CTC technologies with model cell lines
      that express both high and low levels of EpCAM. 

PMID- 26302177
TI  - Malignant progression to anaplastic meningioma: Neuropathology, molecular
      pathology, and experimental models.
AB  - Meningioma is a common adult intracranial tumor, and while several cases are
      considered benign, a subset is malignant with biologically aggressive behavior
      and is refractory to current treatment strategies of combined surgery and
      radiotherapy. Anaplastic meningiomas are quite aggressive and correspond to a
      World Health Organization (WHO) Grade III tumor. This highly aggressive phenotype
      mandates the need for more efficacious therapies. Designing rational therapies
      for treatment will have its foundation in the biologic understanding of involved
      genes and molecular pathways in these types of tumors. Anaplastic meningiomas
      (WHO Grade III) can arise from malignant transformation of lower grade (WHO Grade
      I/II) tumors, however there is an incomplete understanding of specific genetic
      drivers of malignant transformation in these tumors. Here, the current
      understanding of anaplastic meningiomas is reviewed in the context of human
      neuropathologic specimens and small animal models. 

PMID- 26302175
TI  - Relationship between female genital tract infections, mucosal interleukin-17
      production and local T helper type 17 cells.
AB  - T helper type 17 (Th17) cells play an important role in immunity to fungal and
      bacterial pathogens, although their role in the female genital tract, where
      exposure to these pathogens is common, is not well understood. We investigated
      the relationship between female genital tract infections, cervicovaginal
      interleukin-17 (IL-17) concentrations and Th17 cell frequencies. Forty-two
      cytokines were measured in cervicovaginal lavages from HIV-uninfected and HIV
      infected women. Frequencies of Th17 cells (CD3(+) CD4(+) IL-17a(+)) were
      evaluated in cervical cytobrushes and blood by flow cytometry. Women were
      screened for Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium,
      Trichomonas vaginalis and herpes simplex virus 2 by PCR, and candidal infections
      and bacterial vaginosis by Gram stain. Women with bacterial sexually transmitted
      infections (STIs), specifically chlamydia and gonorrhoea, had higher genital IL
      17 concentrations than women with no STI, whereas women with candidal
      pseudohyphae/spores had lower IL-17 concentrations compared with women without
      candidal infections. Viral STIs (herpes simplex virus 2 and HIV) were not
      associated with significant changes in genital IL-17 concentrations. Genital IL
      17 concentrations correlated strongly with other inflammatory cytokines and
      growth factors. Although Th17 cells were depleted from blood during HIV
      infection, cervical Th17 cell frequencies were similar in HIV-uninfected and HIV
      infected women. Cervical Th17 cell frequencies were also not associated with STIs
      or candida, although few women had a STI. These findings suggest that IL-17
      production in the female genital tract is induced in response to bacterial but
      not viral STIs. Decreased IL-17 associated with candidal infections suggests that
      candida may actively suppress IL-17 production or women with dampened IL-17
      responses may be more susceptible to candidal outgrowth.

PMID- 26302176
TI  - Finding mouse models of human lymphomas and leukemia's using the Jackson
      laboratory mouse tumor biology database.
AB  - Many mouse models have been created to study hematopoietic cancer types. There
      are over thirty hematopoietic tumor types and subtypes, both human and mouse,
      with various origins, characteristics and clinical prognoses. Determining the
      specific type of hematopoietic lesion produced in a mouse model and identifying
      mouse models that correspond to the human subtypes of these lesions has been a
      continuing challenge for the scientific community. The Mouse Tumor Biology
      Database (MTB; http://tumor.informatics.jax.org) is designed to facilitate use of
      mouse models of human cancer by providing detailed histopathologic and molecular
      information on lymphoma subtypes, including expertly annotated, on line, whole
      slide scans, and providing a repository for storing information on and querying
      these data for specific lymphoma models. 

PMID- 26302178
TI  - Arsenic toxi-RNomics has the ability to tailor the host immune response.
AB  - Arsenic biology has caught the imagination of scientists across the globe because
      of its unique association with degenerative diseases in general and cancer in
      particular. Recent findings have added a new dimension to arsenic biology by
      revealing that most of the arsenic epigenomic effects are mediated through its
      ability to induce cellular miR-2909 expression at low doses. The present study
      was addressed to explore the molecular link that might exist between arsenic
      exposure, miR-2909 RNomics involving immunomodulatory genes and effector IgA
      class switching, revealed that arsenic-exposed Balb/c mice exhibited predominant
      Th1 immune response coupled with effector IgA class switching thereby tailoring
      their immune system to ensure increased risk to infections and chronic diseases
      like cancer. 

PMID- 26302179
TI  - [Current Guidelines to Prevent Obesity in Childhood and Adolescence].
AB  - BACKGROUND: Current guidelines for the prevention of obesity in childhood and
      adolescence are presented. METHODS: A literature search was performed in Medline
      via PubMed, and appropriate studies were analysed. RESULTS: Programs to prevent
      childhood obesity were to date mainly school-based. Effects were limited to date.
      Analyses tailored to different age groups show that prevention programs have the
      best effects in younger children (< 12 years). Evidence based recommendations for
      preschool- and early school age imply the need for interventions addressing
      parents and teachers alike. During adolescence, school-based interventions were
      most effective when adolescents were directly addressed. To date, obesity
      prevention programs have mainly focused on behavior oriented prevention.
      Recommendations for condition oriented prevention have been suggested by the
      German Alliance of Non-communicable Diseases and include one hour of physical
      activity at school, promotion of healthy food choices by taxing unhealthy foods,
      mandatory quality standards for meals at kindergarten and schools as well as a
      ban on unhealthy food advertisement addressing children. CONCLUSION: Behavior
      oriented prevention programs showed hardly any or only limited effects in the
      long term. Certain risk groups for the development of obesity are not reached
      effectively by available programs. Due to the heterogeneity of available studies,
      universally valid conclusions cannot be drawn. The combination with condition
      oriented prevention, which has to counteract on an obesogenic environment, is
      crucial for sustainable success of future obesity prevention programs.

PMID- 26302180
TI  - Diacylglycerol kinase-zeta regulates mTORC1 and lipogenic metabolism in cancer
      cells through SREBP-1.
AB  - Diacylglycerol kinases (DGKs) transform diacylglycerol (DAG) into phosphatidic
      acid (PA), balancing the levels of these key metabolic and signaling lipids. We
      previously showed that PA derived from the DGKzeta isoform promotes mammalian
      target of rapamycin complex 1 (mTORC1) activation. This function might be crucial
      for the growth and survival of cancer cells, especially for those resistant to
      the allosteric mTOR inhibitor rapamycin. How this positive function of DGKzeta
      coordinates with DAG metabolism and signaling is unknown. In this study, we used
      a rapamycin-resistant colon cancer cell line as a model to address the role of
      DGKzeta in tumor cells. We found that DGKzeta predominated over other PA sources
      such as DGKalpha or phospholipase D to activate mTORC1, and that its activity was
      a component of the rapamycin-induced feedback loops. We show that the DGKzeta DAG
      consuming function is central to cell homeostasis, as DAG negatively regulates
      levels of the lipogenic transcription factor SREBP-1. Our findings suggest a
      model in which simultaneous regulation of DAG and PA levels by DGKzeta is
      integrated with mTOR function to maintain tumor cell homeostasis; we provide new
      evidence of the crosstalk between mTOR and lipid metabolism that will be
      advantageous in the design of drug therapies. 

PMID- 26302181
TI  - Effects of a novel porphyrin-based photosensitizer on sensitive and multidrug
      resistant human gastric cancer cell lines.
AB  - Photodynamic therapy (PDT) has been considered to be a possible candidate
      approach in combating multidrug resistance (MDR) phenomenon during the treatment
      of cancer. To investigate the photocytotoxicity of a novel porphyrin-based
      photosensitizer, meso-5-[rho-DTPA-aminophenyl]-10, 15, 20-triphenyl-porhyrin
      (DTP) (Fig. 1A), on MDR cells, the intracellular DTP uptake, phototoxicity and
      subcellular DTP localization were studied by using a human gastric cancer MGC803
      cell line and its paclitaxel selected subline MGC803/PA expressing MDR phenotype.
      No significant difference was observed in intracellular DTP accumulation between
      sensitive and resistant cell lines after exposure to 1.56 MUM concentration for
      6h. DTP-PDT induced significant photocytotoxicity on both MGC803 and MGC803/PA
      cell lines and the photokilling was greater in MGC803 cell line in comparison to
      MGC803/PA. The fluence that caused 50% cell death was 4.42 and 6.29 J/cm(2) in
      MGC803 and MGC803/PA cell lines, respectively. The presence of Pgp inhibitors
      verapamil and cyclosporin A could not modify the intracellular DTP level in
      MGC803/PA cell line and the phototoxic effects. DTP was localized at lysosomes of
      MGC803 cell line but at lysosomes and mitochondria of MGC803/PA. Our results
      indicated that DTP-mediated PDT could eradicate gastric cancer cells whether or
      not they express MDR although the efficacy is slightly reduced in the MDR cells.
      The photokilling in MDR cells could not be altered by MDR inhibitor verapamil.
      The slightly different photocytotoxicity between sensitive and resistant cell
      lines could not explained by classical Pgp MDR and might be attributed to the
      differential intracellular DTP localization sites.

PMID- 26302182
TI  - An Unexpected Cause of Anemia in a Kidney Transplant Recipient.

PMID- 26302183
TI  - An Unusual Cause of a Large Liver Abscess.

PMID- 26302184
TI  - An Unusual Cause of Cushing's Syndrome and Virilization.

PMID- 26302185
TI  - Tissue factor pathway inhibitor gene transfer prevents vascular smooth muscle
      cell proliferation by interfering with the MCP-3/CCR2 pathway.
AB  - Increased vascular smooth muscle cell (VSMC) proliferation substantially
      contributes to the pathogenesis of atherosclerosis and intimal hyperplasia after
      vascular injury. The importance of inflammation in VSMC proliferation is now
      being recognized. Preventing the inflammatory response is one therapeutic
      strategy that can be used to inhibit atherosclerosis in the clinic. The present
      study, using RNA interference and gene transfer techniques, was conducted to
      investigate the effect of monocyte chemotactic protein-3 (MCP-3) on VSMC
      proliferation that is a result of TNF-alpha stimulation, and whether
      overexpression of the tissue factor pathway inhibitor (TFPI) gene could prevent
      VSMC proliferation by blocking the MCP-3/CC chemokine receptor 2 (CCR2) pathway.
      Mouse VSMCs were infected in vitro with recombinant adenoviruses containing
      either mouse MCP-3-shRNA (Ad-MCP-3-shRNA), the TFPI gene (Ad-TFPI), or the
      negative control, which was shRNA encoding the sequence for EGFP (Ad-EGFP) or
      DMEM only. The cells were then stimulated with TNF-alpha for different time
      periods on the third day after gene transfer. The data show that VSMC
      proliferation in the Ad-MCP-3-shRNA and Ad-TFPI groups was markedly decreased
      using BrdU ELISA and MTT assays; MCP-3-shRNA and TFPI inhibited the expression of
      MCP-3 and CCR2 after long-term stimulation and inhibited the phosphorylation of
      ERK1/2 and AKT after short-term stimulation, as shown by ELISA and western blot
      analysis. This study provides convincing evidence that clarifies the effect of
      the proinflammatory factor MCP-3 in promoting VSMC proliferation. Our data also
      show, for the first time, that TFPI has an anti-proliferative role in TNF-alpha
      stimulated-VSMCs at least partly by interfering with the MCP-3/CCR2 pathway and
      then via suppression of the ERK1/2 and PI3K/AKT signaling pathways. We conclude
      that TFPI gene transfer may be a safe and effective therapeutic tool for treating
      atherosclerosis and intimal hyperplasia. 

PMID- 26302186
TI  - Lipoxin A4 activates alveolar epithelial sodium channel gamma via the microRNA
      21/PTEN/AKT pathway in lipopolysaccharide-induced inflammatory lung injury.
AB  - Lipoxin A4 (LXA4), as an endogenously produced lipid mediator, promotes the
      resolution of inflammation. Previously, we demonstrated that LXA4 stimulated
      alveolar fluid clearance through alveolar epithelial sodium channel gamma (ENaC
      gamma). In this study, we sought to investigate the mechanisms of LXA4 in
      modulation of ENaC-gamma in lipopolysaccharide (LPS)-induced inflammatory lung
      injury. miR-21 was upregulated during an LPS challenge and downregulated by LXA4
      administration in vivo and in vitro. Serum miR-21 concentration was also elevated
      in acute respiratory distress syndrome patients as compared with healthy
      volunteers. LPS increased miR-21 expression by activation of activator protein 1
      (AP-1). In A549 cells, miR-21 upregulated phosphorylation of AKT activation via
      inhibition of phosphatase and tensin homolog (PTEN), and therefore reduced the
      expression of ENaC-gamma. In contrast, LXA4 reversed LPS-inhibited ENaC-gamma
      expression through inhibition of AP-1 and activation of PTEN. In addition, an miR
      21 inhibitor mimicked the effects of LXA4; overexpression of miR-21 abolished the
      protective effects of LXA4. Finally, both AKT and ERK inhibitors (LY294002 and
      UO126) blocked effects of LPS on the depression of ENaC-gamma. However, LXA4 only
      inhibited LPS-induced phosphorylation of AKT. In summary, LXA4 activates ENaC
      gamma in part via the miR-21/PTEN/AKT signaling pathway. 

PMID- 26302187
TI  - Involvement of ZEB1 and Snail1 in excessive production of extracellular matrix in
      Fuchs endothelial corneal dystrophy.
AB  - Fuchs endothelial corneal dystrophy (FECD) due to corneal endothelial cell
      degeneration is a major cause of corneal transplantation. It is characterized by
      abnormal deposition of extracellular matrix (ECM), such as corneal guttae,
      accompanied by a loss of endothelial cells. Although recent studies have revealed
      several genomic factors, the molecular pathophysiology of FECD has not yet been
      revealed. In this study, we establish a cellular in vitro model by using
      immortalized corneal endothelial cells obtained from late-onset FECD and control
      patients and examined the involvement of epithelial mesenchymal transition (EMT)
      on excessive ECM production. We demonstrate that the EMT-inducing genes ZEB1 and
      SNAI1 were highly expressed in corneal endothelial cells in FECD and were
      involved in excessive production of ECM proteins, such as type I collagen and
      fibronectin through the transforming growth factor (TGF)-beta signaling pathway.
      Furthermore, we found that SB431542, a specific inhibitor of TGF-beta type I ALK
      receptors, suppressed the expression of ZEB1 and Snail1 followed by reduced
      production of ECM. These findings suggest that increased expression levels of
      ZEB1 and Snail1 in FECD cells were responsible for an increased responsiveness to
      TGF-beta present in the aqueous humor and excessive production of ECM. In
      addition, these results suggest that the regulation of EMT-related genes by
      blocking the TGF-beta signaling pathway may be a feasible therapeutic strategy
      for FECD. 

PMID- 26302189
TI  - PREDICTORS AND TRENDS OF GROSS MOTOR SKILL PERFORMANCE IN AT-RISK ELEMENTARY
      SCHOOL-AGED CHILDREN.
AB  - -The purpose of this study was to examine the predictors and trends of gross
      motor skills in children from low-income families. The participants were 1,460
      children (M age=8.39 yr., SD=1.83; K-6th grade) recruited from three Title I
      schools. The Test of Gross Motor Development-2nd Edition (TGMD-2) assessed motor
      skills, FITNESSGRAM assessed health-related fitness, and pedometers and
      accelerometers measured moderate-to-vigorous physical activity (MVPA). Multi
      level modeling revealed that TGMD-2 scores predicted aerobic capacity, but no
      other relationships were found with other Healthy Fitness Zone parameters or
      MVPA. TGMD-2 performance was 4.8 and 4.7% greater in successively higher grade
      levels for girls and boys, respectively. In conclusion, TGMD-2 scores predict
      aerobic capacity and TGMD-2 scores improved between 4 and 5% in older grade
      cohorts separated by 1 year.

PMID- 26302188
TI  - Curcumin inhibits cobalt chloride-induced epithelial-to-mesenchymal transition
      associated with interference with TGF-beta/Smad signaling in hepatocytes.
AB  - Epithelial-mesenchymal transition (EMT) occurs during adult tissue remodeling
      responses including carcinogenesis and fibrosis. Existing evidence reveals that
      hepatocytes can undergo EMT in adult liver, which is critically involved in
      chronic liver injury. We herein established a hypoxia-induced EMT model in human
      LO2 hepatocytes treated with cobalt chloride (CoCl2) in vitro, and evaluated the
      effects of curcumin, a natural antifibrotic compound, on hepatocyte EMT and
      explored the underlying molecular mechanisms. We found that CoCl2 at non-toxic
      doses induced a mesenchymal cell phenotype in hepatocytes and upregulated several
      mesenchymal markers including alpha-smooth muscle actin, vimentin, N-cadherin,
      fibronectin and Snail (an EMT-related transcription factor), but downregulated
      the epithelial marker E-cadherin in hepatocytes. However, curcumin reversed the
      morphological changes, abrogated the increased expression of mesenchymal markers,
      and rescued E-cadherin expression in CoCl2-treated hepatocytes, suggesting the
      inhibition of hepatocyte EMT in vitro. We further found that curcumin interfered
      with the transforming growth factor-beta (TGF-beta) signaling by reducing the
      expression of TGF-beta receptor I and inhibiting the expression and
      phosphorylation of Smad2 and Smad3. Use of SB431542, a specific inhibitor of TGF
      beta receptor I, demonstrated that interference with the TGF-beta/Smad pathway
      was associated with curcumin suppression of hepatocyte EMT. Our in vivo data
      showed that curcumin affected hepatic EMT in rat fibrotic liver caused by carbon
      tetrachloride, which was associated with the inhibition of TGF-beta/Smad
      signaling. These findings characterized a novel mechanism by which curcumin
      modulated hepatocyte EMT implicated in treatment of liver fibrosis. 

PMID- 26302190
TI  - EFFECT OF ENERGY DRINKS ON SELECTED FINE MOTOR TASKS.
AB  - This study assessed the effect of energy shots on selected fine motor tasks. The
      participants were college-age male (n=19; M age=20.5 yr., SD=0.7) and female
      (n=21; M age=21.1 yr., SD=0.7) volunteers who were assessed on hand steadiness,
      choice reaction time, rotary pursuit, and simple reaction time. The energy shots
      group scored significantly poorer on the hand steadiness tests and significantly
      better on choice reaction time and simple reaction time tests. The enhanced
      reaction time and disruption in hand steadiness afforded by energy shots would
      not be apparent in many gross motor activities, but it is possible that reaction
      time improvement could be beneficial in sports that require quick, reflexive
      movements. However, the potential adverse psychological and physiological effects
      warrant discretionary use of such products.

PMID- 26302191
TI  - DEVELOPING NUMERICAL ABILITY IN CHILDREN WITH MATHEMATICAL DIFFICULTIES USING
      ORIGAMI (.).
AB  - Certain aspects of numerical processing show a connection with spatial abilities.
      Spatial abilities may be enhanced through the practice of origami. It is possible
      that the development of spatial abilities will support the development of
      numerical processing. The goal was to investigate whether spatial and numerical
      skills can be developed using origami and the folding of three-dimensional
      shapes. During the course of the 10-wk. training program, consisting of weekly 60
      min. sessions, the performance of children with mathematical difficulties showed
      considerable improvement in spatial and numerical tasks as compared to the
      control group of children with mathematical difficulties.

PMID- 26302192
TI  - THE IMPORTANCE OF NEGATIVE ACCELERATION OF THE LOAD IN FREE-STYLE LIFTING.
AB  - Lifters may use negative acceleration in lifting a very light load. Body
      kinematic data were recorded in 10 participants lifting a 114 g box. Vertical
      position and acceleration of the center of mass and angle of the thigh to a
      vertical line were calculated. Acceleration data between the positions of the
      body when the thighs were horizontal and as the knees extended to an angle of 45
      degrees  indicated that negative acceleration was present at 68.9% of time
      points, more than predicted by chance.

PMID- 26302194
TI  - ARM MOVEMENT AS A CUE FOR THE ESTIMATION OF VISUAL LOCATION.
AB  - Two experiments including 24 (M age=29 yr., SD=9; 6 men) and 25 participants (M
      age=27 yr., SD=9; 8 men), respectively, examined how arm movement extent affects
      the perception of visual locations. Linear arm movements were performed on a
      horizontal plane from a start position until an auditory signal occurred.
      Subsequently, the position of a visual target located along the movement path was
      judged. The target was judged as further away with an increase in movement
      extent. The results indicated that motor-related signals are taken into account
      in visual perception of locations. There were no indications, though, that
      changes of location perception prompted subsequent changes of action planning,
      which demonstrates the short-term nature of action-induced plasticity of space
      perception under the present conditions.

PMID- 26302193
TI  - THE RELATIVE AGE EFFECT IN COMBAT SPORTS: AN ANALYSIS OF OLYMPIC JUDO ATHLETES,
      1964-2012.
AB  - This study assessed the relative age effect (RAE) in judo athletes who
      participated in the Olympic Games from 1964 to 2012. The names and birthdates of
      the Olympic judo athletes were collected from open-access websites. Data from
      male (n=1,762) and female (n=665) competitors were analyzed separately. Chi
      squared tests were performed to investigate REA in medalists, and by weight
      categories and sexes. When the analyses used semesters to divide the period when
      the athletes were born, a RAE was found in male heavyweight athletes and male
      medallists. Thus, in a selected group of judo athletes who had participated at
      the highest competitive level, RAEs were present in both athletes who won Olympic
      medals and heavyweight athletes in the male group.

PMID- 26302195
TI  - Directly Observing the Lipid-Dependent Self-Assembly and Pore-Forming Mechanism
      of the Cytolytic Toxin Listeriolysin O.
AB  - Listeriolysin O (LLO) is the major virulence factor of Listeria monocytogenes and
      a member of the cholesterol-dependent cytolysin (CDC) family. Gram-positive
      pathogenic bacteria produce water-soluble CDC monomers that bind cholesterol
      dependent to the lipid membrane of the attacked cell or of the phagosome,
      oligomerize into prepores, and insert into the membrane to form transmembrane
      pores. However, the mechanisms guiding LLO toward pore formation are poorly
      understood. Using electron microscopy and time-lapse atomic force microscopy, we
      show that wild-type LLO binds to membranes, depending on the presence of
      cholesterol and other lipids. LLO oligomerizes into arc- or slit-shaped
      assemblies, which merge into complete rings. All three oligomeric assemblies can
      form transmembrane pores, and their efficiency to form pores depends on the
      cholesterol and the phospholipid composition of the membrane. Furthermore, the
      dynamic fusion of arcs, slits, and rings into larger rings and their formation of
      transmembrane pores does not involve a height difference between prepore and
      pore. Our results reveal new insights into the pore-forming mechanism and
      introduce a dynamic model of pore formation by LLO and other CDC pore-forming
      toxins. 

PMID- 26302196
TI  - Parsing.
AB  - Research on syntax and parsing played a central role in the cognitive revolution
      and continues to occupy a central position in the study of language. While
      linguistically driven theories of syntactic representation have not proven
      sufficient to predict and explain the full range of experimental outcomes, they
      have provided invaluable insights to language researchers. Greater success has
      been achieved by combining insights from linguistics and cognitive psychology.
      Such approaches began to emerge in the 1970s, with the advent of serial, modular,
      syntax-first approaches, such as the garden-path theory, that were
      computationally tractable and plausible given human resource limitations. The
      'second wave' of syntactic parsing theories arose as an important component of
      connectionist/neural network-inspired research in the 1980s and 1990s. These
      accounts differed from first-generation accounts in that they viewed syntactic
      parsing as being one component of a massively interactive parallel-processing
      system. According to such accounts, the parser responds to a wide variety of
      lexical and contextual influences, and evidence for such effects can be found in
      experiments involving verb subcategory preferences, lexical-semantic properties
      of words in important syntactic positions, and discourse and visual context.
      Recent emerging theories have added new perspectives by focusing on multiple cues
      to meaning, redundancy at lexical-semantic and syntactic levels of analysis, the
      importance of anticipatory processes, and the importance of experience in adult
      comprehenders. Thus, parsing theory continues to evolve and we can expect this
      area of inquiry to remain lively for the foreseeable future. WIREs Cogni Sci 2011
      2 353-364 DOI: 10.1002/wcs.112 For further resources related to this article,
      please visit the WIREs website. 

PMID- 26302197
TI  - Children's episodic memory.
AB  - Episodic memory develops during childhood and adolescence. This trajectory
      depends on several underlying processes. In this article, we first discuss the
      development of the basic binding processes (e.g., the processes by which elements
      are bound together to form a memory episode) and control processes (e.g.,
      reasoning and metamemory processes) involved in episodic remembering. Then, we
      discuss the role of these processes in false-memory formation. In the subsequent
      sections, we examine the neural substrates of the development of episodic memory.
      Finally, we discuss atypical development of episodic memory. As we proceed
      through the article, we suggest potential avenues for future research. WIREs
      Cogni Sci 2011 2 365-373 DOI: 10.1002/wcs.114 For further resources related to
      this article, please visit the WIREs website. 

PMID- 26302198
TI  - Qualitative modeling.
AB  - Qualitative modeling concerns the representations and reasoning that people use
      to understand continuous aspects of the world. Qualitative models formalize
      everyday notions of causality and provide accounts of how to ground symbolic,
      relational representations in perceptual processes. This article surveys the
      basic ideas of qualitative modeling and their applications from a cognitive
      science perspective. It describes the basic principles of qualitative modeling,
      and a variety of qualitative representations that have been developed for
      quantities and for relationships between them, providing a kind of qualitative
      mathematics. Three ontological frameworks for organizing modeling knowledge
      (processes, components, and field) are summarized, along with research on
      automatically assembling models for particular tasks from such knowledge.
      Qualitative simulation and how it carves up time into meaningful units is
      discussed. We discuss several accounts of causal reasoning about dynamical
      systems, based on different choices of qualitative mathematics and ontology.
      Qualitative spatial reasoning is explored, both in terms of relational systems
      and visual reasoning. Applications of qualitative models of particular interest
      to cognitive scientists are described, including how they have been used to
      capture the expertise of scientists and engineers and how they have been used in
      education. Open questions and frontiers are also discussed, focusing on
      relationships between ideas developed in the qualitative modeling community and
      other areas of cognitive science. WIREs Cogni Sci 2011 2 374-391 DOI:
      10.1002/wcs.115 For further resources related to this article, please visit the
      WIREs website. 

PMID- 26302199
TI  - Neural basis of visual selective attention.
AB  - Attentional modulation along the object-recognition pathway of the cortical
      visual system of primates has been shown to consist of enhanced representation of
      the retinal input at a specific location in space, or of objects located anywhere
      in the visual field which possess a critical object feature. Moreover, selective
      attention mechanisms allow the visual system to resolve competition among
      multiple objects in a crowded scene in favor of the object that is relevant for
      the current behavior. Finally, selective attention affects the spontaneous
      activity of neurons as well as their visually driven responses, and it does so
      not only by modulating the spiking activity of individual neurons, but also by
      modulating the degree of coherent firing within the critical neuronal
      populations. WIREs Cogni Sci 2011 2 392-407 DOI: 10.1002/wcs.117 For further
      resources related to this article, please visit the WIREs website. 

PMID- 26302200
TI  - The biological basis of audition.
AB  - Audition is one of the fundamental extrasensory percepts in mammals. Two of the
      primary objectives of audition are to determine where sounds originate from in
      space and what those sounds are. Neural processing of acoustic signals, which are
      commonly quite complex under natural conditions, is extensive in the brainstem,
      midbrain, and thalamus. This processing extracts multiple salient features that
      are then transmitted to the cerebral cortex. The cerebral cortex is a necessary
      neural structure for audition, or the perception of acoustic auditory objects
      and/or events. This entry will review the early processing along the ascending
      auditory central nervous system from the cochlea to the cerebral cortex. The
      neural mechanisms of audition will then be explored for spatial and non-spatial
      perception, drawing largely on examples from non-human primates, but insights
      gained from other mammalian species will also be covered. How these models relate
      to current studies in human subjects, using both functional imaging and invasive
      techniques, will also be explored as well as the types of future studies that
      will enable us to better understand the neural mechanisms of audition. WIREs
      Cogni Sci 2011 2 408-418 DOI: 10.1002/wcs.118 For further resources related to
      this article, please visit the WIREs website. 

PMID- 26302201
TI  - Bayesian approaches to sensory integration for motor control.
AB  - The processing of sensory information is fundamental to the basic operation of
      the nervous system. Our nervous system uses this sensory information to gain
      knowledge of our bodies and the world around us. This knowledge is of great
      importance as it provides the coherent and accurate information necessary for
      successful motor control. Yet, all this knowledge is of an uncertain nature
      because we obtain information only through our noisy sensors. We are thus faced
      with the problem of integrating many uncertain pieces of information into
      estimates of the properties of our bodies and the surrounding world. Bayesian
      approaches to estimation formalize the problem of how this uncertain information
      should be integrated. Utilizing this approach, many studies make predictions that
      faithfully predict human sensorimotor behavior. WIREs Cogni Sci 2011 2 419-428
      DOI: 10.1002/wcs.125 For further resources related to this article, please visit
      the WIREs website. 

PMID- 26302202
TI  - Evo Devo and cognitive science.
AB  - Evo Devo (evolutionary developmental) biology forges a synthesis of evolutionary
      and developmental processes. Evo Devo is the result of collaborative work of
      evolutionary and developmental biologists after the discovery of regulatory genes
      that human beings share with many other animals, including fruit flies, frogs,
      and rats. Compared to traditional evolutionary biologists, Evo Devo biologists
      focus on processes underlying the generation of evolutionary novelties, rather
      than on how natural selection changes gene frequencies in populations and how
      organisms are adapted to their environment. Evo Devo biologists try to answer
      questions such as: How do novel structures arise? Which mechanisms facilitate or
      constrain evolutionary change? In this article we argue that insights from Evo
      Devo research can contribute to the understanding of the evolution and
      development of cognition, and of the origin of neurocognitive disorders. We
      discuss three major Evo Devo topics: modularity, evolvability, and developmental
      constraints. We argue that each of these topics are relevant for research in
      cognitive science, and we argue that interdisciplinary research is necessary in
      order to unravel the evolutionary and developmental mechanisms of cognitive
      traits and disorders. WIREs Cogni Sci 2011 2 429-440 DOI: 10.1002/wcs.137 For
      further resources related to this article, please visit the WIREs website. 

PMID- 26302203
TI  - Molecular genetics and molecular biology of dyslexia.
AB  - Developmental dyslexia has been recognized as a distinct entity among learning
      disabilities as early as the late 1800s and its partially genetic nature has been
      firmly established by family and twin studies. The application of genetic mapping
      and molecular cloning methods has revealed specific genes that contribute to the
      genetic risk, but those known now do not yet suffice for explaining all of it.
      More importantly, the first genes, some of them found by the study of rare
      families, have indicated specific neurodevelopmental processes important for the
      development of dyslexia, including control of neuronal migration for the DYX1C1,
      DCDC2, and KIAA0319 genes, and a role of axonal and dendritic guidance suggested
      by the ROBO1 gene. I anticipate that forthcoming research within only a few years
      will yield molecular networks with fundamental roles in the molecular biology of
      dyslexia, and may aid in resolving relationships between comorbid disorders.
      WIREs Cogni Sci 2011 2 441-448 DOI: 10.1002/wcs.138 For further resources related
      to this article, please visit the WIREs website. 

PMID- 26302204
TI  - Small molecule inhibition of Csk alters affinity recognition by T cells.
AB  - The C-terminal Src kinase (Csk), the primary negative regulator of Src-family
      kinases (SFK), plays a crucial role in controlling basal and inducible receptor
      signaling. To investigate how Csk activity regulates T cell antigen receptor
      (TCR) signaling, we utilized a mouse expressing mutated Csk (Csk(AS)) whose
      catalytic activity is specifically and rapidly inhibited by a small molecule.
      Inhibition of Csk(AS) during TCR stimulation led to stronger and more prolonged
      TCR signaling and to increased proliferation. Inhibition of Csk(AS) enhanced
      activation by weak but strictly cognate agonists. Titration of Csk inhibition
      revealed that a very small increase in SFK activity was sufficient to potentiate
      T cell responses to weak agonists. Csk plays an important role, not only in basal
      signaling, but also in setting the TCR signaling threshold and affinity
      recognition. 

PMID- 26302207
TI  - Magnetotransport Properties of Cd3As2 Nanostructures.
AB  - Three-dimensional (3D) topological Dirac semimetal has a linear energy dispersion
      in 3D momentum space, and it can be viewed as an analogue of graphene. Extensive
      efforts have been devoted to the understanding of bulk materials, but yet it
      remains a challenge to explore the intriguing physics in low-dimensional Dirac
      semimetals. Here, we report on the synthesis of Cd3As2 nanowires and nanobelts
      and a systematic investigation of their magnetotransport properties. Temperature
      dependent ambipolar behavior is evidently demonstrated, suggesting the presence
      of finite-size of bandgap in nanowires. Cd3As2 nanobelts, however, exhibit
      metallic characteristics with a high carrier mobility exceeding 32,000 cm(2) V(
      1) s(-1) and pronounced anomalous double-period Shubnikov-de Haas (SdH)
      oscillations. Unlike the bulk counterpart, the Cd3As2 nanobelts reveal the
      possibility of unusual change of the Fermi sphere owing to the suppression of the
      dimensionality. More importantly, their SdH oscillations can be effectively tuned
      by the gate voltage. The successful synthesis of Cd3As2 nanostructures and their
      rich physics open up exciting nanoelectronic applications of 3D Dirac semimetals.

PMID- 26302206
TI  - Neuropilin-2/Semaphorin-3F-mediated repulsion promotes inner hair cell
      innervation by spiral ganglion neurons.
AB  - Auditory function is dependent on the formation of specific innervation patterns
      between mechanosensory hair cells (HCs) and afferent spiral ganglion neurons
      (SGNs). In particular, type I SGNs must precisely connect with inner HCs (IHCs)
      while avoiding connections with nearby outer HCs (OHCs). The factors that mediate
      these patterning events are largely unknown. Using sparse-labeling and time-lapse
      imaging, we visualized for the first time the behaviors of developing SGNs
      including active retraction of processes from OHCs, suggesting that some type I
      SGNs contact OHCs before forming synapses with IHCs. In addition, we demonstrate
      that expression of Semaphorin-3F in the OHC region inhibits type I SGN process
      extension by activating Neuropilin-2 receptors expressed on SGNs. These results
      suggest a model in which cochlear innervation patterns by type I SGNs are
      determined, at least in part, through a Semaphorin-3F-mediated inhibitory signal
      that impedes processes from extending beyond the IHC region. 

PMID- 26302205
TI  - The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing
      stereocilia and is essential for hearing.
AB  - The precise assembly of inner ear hair cell stereocilia into rows of increasing
      height is critical for mechanotransduction and the sense of hearing. Yet, how the
      lengths of actin-based stereocilia are regulated remains poorly understood.
      Mutations of the molecular motor myosin 15 stunt stereocilia growth and cause
      deafness. We found that hair cells express two isoforms of myosin 15 that differ
      by inclusion of an 133-kDa N-terminal domain, and that these isoforms can
      selectively traffic to different stereocilia rows. Using an isoform-specific
      knockout mouse, we show that hair cells expressing only the small isoform
      remarkably develop normal stereocilia bundles. However, a critical subset of
      stereocilia with active mechanotransducer channels subsequently retracts. The
      larger isoform with the 133-kDa N-terminal domain traffics to these specialized
      stereocilia and prevents disassembly of their actin core. Our results show that
      myosin 15 isoforms can navigate between functionally distinct classes of
      stereocilia, and are independently required to assemble and then maintain the
      intricate hair bundle architecture. 

PMID- 26302209
TI  - Heterogeneous Diffusion of Alkanes in the Hierarchical Metal-Organic Framework NU
      1000.
AB  - The metal-organic framework (MOF) NU-1000 is a hierarchical material that
      comprises both micropores and mesopores in its crystalline structure. Because the
      pore structure is perfectly defined, NU-1000 is an interesting material for
      improving our understanding of diffusion in hierarchically structured materials.
      Here, we present molecular dynamics simulations aimed at probing the transport
      properties of n-alkanes in NU-1000 and introduce methods from the microrheology
      literature for analyzing the mean-squared displacements and their spatial
      heterogeneity. Adsorption occurs initially in the smaller channels, and diffusion
      at low loading is limited by interaction between adsorbate and framework atoms.
      The larger channels provide a region of low density where molecules are able to
      diffuse at higher rates predominantly along the channel axes. The disparate size
      of the channels gives rise to heterogeneity in the diffusivity of the guest
      molecules, whereas the asymmetry of the channels leads to anisotropic diffusion.
      Together, the channels form a network of "highways" and "side streets" that
      provide enhanced diffusion in one dimension. 

PMID- 26302208
TI  - Facile Phase Transfer and Surface Biofunctionalization of Hydrophobic
      Nanoparticles Using Janus DNA Tetrahedron Nanostructures.
AB  - Hydrophobic nanoparticles have shown substantial potential for bioanalysis and
      biomedical applications. However, their use is hindered by complex phase transfer
      and inefficient surface modification. This paper reports a facile and universal
      strategy for phase transfer and surface biofunctionalization of hydrophobic
      nanomaterials using aptamer-pendant DNA tetrahedron nanostructures (Apt-tet). The
      Janus DNA tetrahedron nanostructures are constructed by three carboxyl group
      modified DNA strands and one aptamer sequence. The pendant linear sequence is an
      aptamer, in this case AS1411, known to specifically bind nucleolin, typically
      overexpressed on the plasma membranes of tumor cells. The incorporation of the
      aptamers adds targeting ability and also enhances intracellular uptake. Phase
      transfer efficiency using Apt-tet is much higher than that achieved using single
      stranded DNA. In addition, the DNA tetrahedron nanostructures can be programmed
      to permit the incorporation of other functional nucleic acids, such as DNAzymes,
      siRNA, or antisense DNA, allowing, in turn, the construction of promising
      theranostic nanoagents for bioanalysis and biomedical applications. Given these
      unique features, we believe that our strategy of surface modification and
      functionalization may become a new paradigm in phase-transfer-agent design and
      further expand biomedical applications of hydrophobic nanomaterials. 

PMID- 26302210
TI  - Para-toluenesulfonamide induces tongue squamous cell carcinoma cell death through
      disturbing lysosomal stability.
AB  - Para-toluenesulfonamide (PTS) has been implicated with anticancer effects against
      a variety of tumors. In the present study, we investigated the inhibitory effects
      of PTS on tongue squamous cell carcinoma (Tca-8113) and explored the lysosomal
      and mitochondrial changes after PTS treatment in vitro. High-performance liquid
      chromatography showed that PTS selectively accumulated in Tca-8113 cells with a
      relatively low concentration in normal fibroblasts. Next, the effects of PTS on
      cell viability, invasion, and cell death were determined. PTS significantly
      inhibited Tca-8113 cells' viability and invasive ability with increased cancer
      cell death. Flow cytometric analysis and the lactate dehydrogenase release assay
      showed that PTS induced cancer cell death by activating apoptosis and necrosis
      simultaneously. Morphological changes, such as cellular shrinkage, nuclear
      condensation as well as formation of apoptotic body and secondary lysosomes, were
      observed, indicating that PTS might induce cell death through disturbing
      lysosomal stability. Lysosomal integrity assay and western blot showed that PTS
      increased lysosomal membrane permeabilization associated with activation of
      lysosomal cathepsin B. Finally, PTS was shown to inhibit ATP biosynthesis and
      induce the release of mitochondrial cytochrome c. Therefore, our findings provide
      a novel insight into the use of PTS in cancer therapy. 

PMID- 26302211
TI  - Identification of Suitable Reference Genes for Gene Expression Normalization in
      the Quantitative Real-Time PCR Analysis of Sweet Osmanthus (Osmanthus fragrans
      Lour.).
AB  - Quantitative real-time PCR (RT-qPCR), a sensitive technique for quantifying gene
      expression, depends on the stability of the reference gene(s) used for data
      normalization. Several studies examining the selection of reference genes have
      been performed in ornamental plants but none in sweet osmanthus (Osmanthus
      fragrans Lour.). Based on transcriptomic sequencing data from O. fragrans buds at
      four developmental stages, six reference genes (OfACT, OfEF1alpha, OfIDH, OfRAN1,
      OfTUB, and OfUBC2) with stable expression (0.5 to 2 fold change in expression
      levels between any two developmental stages), as well as the commonly used
      reference gene Of18S, were selected as candidates for gene expression
      normalization in the RT-qPCR analysis of O. fragrans. For the normalization of RT
      qPCR with two dyes, SYBR Green and EvaGreen, the expressional stability of seven
      candidate reference genes in 43 O. fragrans samples was analyzed using geNorm,
      NormFinder and BestKeeper. For RT-qPCR using SYBR Green, OfRAN1 and OfUBC2 were
      the optimal reference genes for all samples and different cultivars, OfACT and
      OfEF1alpha were suitable for different floral developmental stages, and OfACT was
      the optimal reference gene for different temperature treatments. The geometric
      mean values of the optimal reference gene pairs for the normalization of RT-qPCR
      are recommended to be used for all samples, different cultivars and different
      floral developmental stages in O. fragrans. For RT-qPCR using EvaGreen, OfUBC2
      was the optimal reference gene for all samples and different cultivars, and OfACT
      was the optimal reference gene for different floral developmental stages and
      different temperature treatments. As the worst reference gene, Of18S should not
      be used as a reference gene in O. fragrans in the future. Our results provide a
      reference gene application guideline for O. fragrans gene expression
      characterization using RT-qPCR. 

PMID- 26302212
TI  - Modifying the Mechanical Properties of Silk Fiber by Genetically Disrupting the
      Ionic Environment for Silk Formation.
AB  - Silks are widely used biomaterials, but there are still weaknesses in their
      mechanical properties. Here we report a method for improving the silk fiber
      mechanical properties by genetic disruption of the ionic environment for silk
      fiber formation. An anterior silk gland (ASG) specific promoter was identified
      and used for overexpressing ion-transporting protein in the ASG of silkworm.
      After isolation of the transgenic silkworms, we found that the metal ion content,
      conformation and mechanical properties of transgenic silk fibers changed
      accordingly. Notably, overexpressing endoplasmic reticulum Ca2+-ATPase in ASG
      decreased the calcium content of silks. As a consequence, silk fibers had more
      alpha-helix and beta-sheet conformations, and their tenacity and extension
      increased significantly. These findings represent the in vivo demonstration of a
      correlation between metal ion content in the spinning duct and the mechanical
      properties of silk fibers, thus providing a novel method for modifying silk fiber
      properties.

PMID- 26302214
TI  - Editorial.

PMID- 26302213
TI  - Evaluating the Effect of Expressing a Peanut Resveratrol Synthase Gene in Rice.
AB  - Resveratrol (Res) is a type of natural plant stilbenes and phytoalexins that only
      exists in a few plant species. Studies have shown that the Res could be
      biosynthesized and accumulated within plants, once the complete metabolic pathway
      and related enzymes, such as the key enzyme resveratrol synthase (RS), existed.
      In this study, a RS gene named PNRS1 was cloned from the peanut, and the activity
      was confirmed in E. coli. Using transgenic approach, the PNRS1 transgenic rice
      was obtained. In T3 generation, the Res production and accumulation were further
      detected by HPLC. Our data revealed that compared to the wild type rice which
      trans-resveratrol was undetectable, in transgenic rice, the trans-resveratrol
      could be synthesized and achieved up to 0.697 MUg/g FW in seedlings and 3.053
      MUg/g DW in seeds. Furthermore, the concentration of trans-resveratrol in
      transgenic rice seedlings could be induced up to eight or four-fold higher by
      ultraviolet (UV-C) or dark, respectively. Simultaneously, the endogenous
      increased of Res also showed the advantages in protecting the host plant from UV
      C caused damage or dark-induced senescence. Our data indicated that Res was
      involved in host-defense responses against environmental stresses in transgenic
      rice. Here the results describes the processes of a peanut resveratrol synthase
      gene transformed into rice, and the detection of trans-resveratrol in transgenic
      rice, and the role of trans-resveratrol as a phytoalexin in transgenic rice when
      treated by UV-C and dark. These findings present new outcomes of transgenic
      approaches for functional genes and their corresponding physiological functions,
      and shed some light on broadening available resources of Res, nutritional
      improvement of crops, and new variety cultivation by genetic engineering. 

PMID- 26302215
TI  - Pathogens and pharmaceuticals in source-separated urine in eThekwini, South
      Africa.
AB  - In eThekwini, South Africa, the production of agricultural fertilizers from human
      urine collected from urine-diverting dry toilets is being evaluated at a
      municipality scale as a way to help finance a decentralized, dry sanitation
      system. The present study aimed to assess a range of human and environmental
      health hazards in source-separated urine, which was presumed to be contaminated
      with feces, by evaluating the presence of human pathogens, pharmaceuticals, and
      an antibiotic resistance gene. Composite urine samples from households enrolled
      in a urine collection trial were obtained from urine storage tanks installed in
      three regions of eThekwini. Polymerase chain reaction (PCR) assays targeted 9
      viral and 10 bacterial human pathogens transmitted by the fecal-oral route. The
      most frequently detected viral pathogens were JC polyomavirus, rotavirus, and
      human adenovirus in 100%, 34% and 31% of samples, respectively. Aeromonas spp.
      and Shigella spp. were frequently detected gram negative bacteria, in 94% and 61%
      of samples, respectively. The gram positive bacterium, Clostridium perfringens,
      which is known to survive for extended times in urine, was found in 72% of
      samples. A screening of 41 trace organic compounds in the urine facilitated
      selection of 12 priority pharmaceuticals for further evaluation. The antibiotics
      sulfamethoxazole and trimethoprim, which are frequently prescribed as prophylaxis
      for HIV-positive patients, were detected in 95% and 85% of samples, reaching
      maximum concentrations of 6800 MUg/L and 1280 MUg/L, respectively. The
      antiretroviral drug emtricitabine was also detected in 40% of urine samples. A
      sulfonamide antibiotic resistance gene (sul1) was detected in 100% of urine
      samples. By coupling analysis of pathogens and pharmaceuticals in geographically
      dispersed samples in eThekwini, this study reveals a range of human and
      environmental health hazards in urine intended for fertilizer production.
      Collection of urine offers the benefit of sequestering contaminants from
      environmental release and allows for targeted treatment of potential health
      hazards prior to agricultural application. The efficacy of pathogen and
      pharmaceutical inactivation, transformation or removal during urine nutrient
      recovery processes is thus briefly reviewed.

PMID- 26302216
TI  - Fate of the fecal indicator Escherichia coli in irrigation with partially treated
      wastewater.
AB  - Treated wastewater reuse is increasing in semi-arid regions as a response to the
      effects of climate change and increased competition for natural water resources.
      Investigating the fate of bacterial indicators is relevant to assess their
      persistence in the environment and possible transfer to groundwater or to the
      food chain. A long-term field-scale experimental campaign and a soil column test
      were carried out to evaluate the fate of the fecal indicator Escherichia coli (E.
      coli) in a cultivated soil when contaminated water resources are used for
      irrigation. For field experiments, fecal contamination was simulated by dosing
      the indicator to the effluent of a membrane bioreactor, thus simulating a
      filtration system's failure, and irrigating a test field where grass was grown.
      The presence of E. coli on grass and topsoil samples was monitored under
      different scenarios. For evaluating the fate of the same indicator in the
      subsoil, a set of soil columns was installed next to the field, operated, and
      monitored for E. coli concentration over time and along depth. Real municipal
      wastewater was used in this case as source of fecal contamination. Results showed
      that short- and medium-term effects on topsoil were strongly dependent on the
      concentration of E. coli in the irrigation water. Limited persistence and no
      relevant accumulation of the indicator on the grass and in the topsoil were
      observed. Watering events performed after fecal contamination did not influence
      significantly the decay in the topsoil, which followed a log-linear model. The
      trend of the E. coli concentrations in the leaching of the soil columns followed
      a log-linear model as well, suggesting bacterial decay as the dominant mechanism
      affecting the underground indicator's concentration.

PMID- 26302217
TI  - Field efficacy evaluation and post-treatment contamination risk assessment of an
      ultraviolet disinfection and safe storage system.
AB  - Inconsistent use of household water treatment and safe storage (HWTS) systems
      reduces their potential health benefits. Ultraviolet (UV) disinfection is more
      convenient than some existing HWTS systems, but it does not provide post
      treatment residual disinfectant, which could leave drinking water vulnerable to
      recontamination. In this paper, using as-treated analyses, we report on the field
      efficacy of a UV disinfection system at improving household drinking water
      quality in rural Mexico. We further assess the risk of post-treatment
      contamination from the UV system, and develop a process-based model to better
      understand household risk factors for recontamination. This study was part of a
      larger cluster-randomized stepped wedge trial, and the results complement
      previously published population-level results of the intervention on diarrheal
      prevalence and water quality. Based on the presence of Escherichia coli
      (proportion of households with >= 1 E. coli/100 mL), we estimated a risk
      difference of -28.0% (95% confidence interval (CI): -33.9%, -22.1%) when
      comparing intervention to control households; -38.6% (CI: -48.9%, -28.2%) when
      comparing post- and pre-intervention results; and -37.1% (CI: -45.2%, -28.9%)
      when comparing UV disinfected water to alternatives within the household. We
      found substantial increases in post-treatment E. coli contamination when
      comparing samples from the UV system effluent (5.0%) to samples taken from the
      storage container (21.1%) and drinking glasses (26.0%). We found that improved
      household infrastructure, additional extractions from the storage container,
      additional time from when the storage container was filled, and increased
      experience of the UV system operator were associated with reductions in post
      treatment contamination. Our results suggest that the UV system is efficacious at
      improving household water quality when used as intended. Promoting safe storage
      habits is essential for an effective UV system dissemination. The drinking glass
      appears to represent a small but significant source of recontamination that is
      likely to impact all HWTS systems.

PMID- 26302218
TI  - Nitrogenous disinfection byproducts in English drinking water supply systems:
      Occurrence, bromine substitution and correlation analysis.
AB  - Despite the recent focus on nitrogenous disinfection byproducts in drinking
      water, there is limited occurrence data available for many species. This paper
      analyses the occurrence of seven haloacetonitriles, three haloacetamides, eight
      halonitromethanes and cyanogen chloride in 20 English drinking water supply
      systems. It is the first survey of its type to compare bromine substitution
      factors (BSFs) between the haloacetamides and haloacetonitriles. Concentrations
      of the dihalogenated haloacetonitriles and haloacetamides were well correlated.
      Although median concentrations of these two groups were lower in chloraminated
      than chlorinated surface waters, median BSFs for both in chloraminated samples
      were approximately double those in chlorinated samples, which is significant
      because of the higher reported toxicity of the brominated species. Furthermore,
      median BSFs were moderately higher for the dihalogenated haloacetamides than for
      the haloacetonitriles. This indicates that, while the dihalogenated
      haloacetamides were primarily generated from hydrolysis of the corresponding
      haloacetonitriles, secondary formation pathways also contributed. Median
      halonitromethane concentrations were remarkably unchanging for the different
      types of disinfectants and source waters: 0.1 MUg . mgTOC(-1) in all cases.
      Cyanogen chloride only occurred in a limited number of samples, yet when present
      its concentrations were higher than the other N-DBPs. Concentrations of cyanogen
      chloride and the sum of the halonitromethanes were not correlated with any other
      DBPs.

PMID- 26302219
TI  - Adsorption capacities of activated carbons for geosmin and 2-methylisoborneol
      vary with activated carbon particle size: Effects of adsorbent and adsorbate
      characteristics.
AB  - The adsorption capacities of nine activated carbons for geosmin and 2
      methylisoborneol (MIB) were evaluated. For some carbons, adsorption capacity
      substantially increased when carbon particle diameter was decreased from a few
      tens of micrometers to a few micrometers, whereas for other carbons, the increase
      of adsorption capacity was small for MIB and moderate for geosmin. An increase of
      adsorption capacity was observed for other hydrophobic adsorbates besides geosmin
      and MIB, but not for hydrophilic adsorbates. The parameter values of a shell
      adsorption model describing the increase of adsorption capacity were negatively
      correlated with the oxygen content of the carbon among other characteristics. Low
      oxygen content indicated low hydrophilicity. The increase of adsorption capacity
      was related to the hydrophobic properties of both adsorbates and activated
      carbons. For adsorptive removal of hydrophobic micropollutants such as geosmin,
      it is therefore recommended that less-hydrophilic activated carbons, such as
      coconut-shell-based carbons, be microground to a particle diameter of a few
      micrometers to enhance their equilibrium adsorption capacity. In contrast,
      adsorption by hydrophilic carbons or adsorption of hydrophilic adsorbates occur
      in the inner pores, and therefore adsorption capacity is unchanged by particle
      size reduction. 

PMID- 26302220
TI  - Evaluation of a Voluntary Worksite Weight Loss Program on Metabolic Syndrome.
AB  - BACKGROUND: Health care costs increase with the presence of metabolic syndrome
      and present a significant burden to companies throughout the world. Identifying
      effective behavioral programs within the workplace can reduce health care costs.
      We examined the effect of a voluntary worksite program on weight loss and
      metabolic syndrome. METHODS: Participants (N = 3880, from 93 companies)
      volunteered within their workplaces to participate in a 10-week weight loss
      program (Naturally Slim) focused on self-monitoring, eating behaviors,
      understanding hunger signals, reducing refined carbohydrate and sugar intake, and
      increasing protein intake to 25%-30%. Primary outcomes included weight loss and
      metabolic syndrome prevalence. Secondary analyses examined the individual
      components of metabolic syndrome and a categorical analysis within each World
      Health Organization body mass index category. RESULTS: Overall, women and men
      lost 9.4 (-4.8%) and 13.2 pounds (-5.8%), respectively. Each metabolic risk
      factor for both genders had a significant improvement but men exhibited the
      largest relative improvement for each risk factor. At baseline, 43% of women and
      52% of men presented with metabolic syndrome, which was reduced to 30% in women
      and 26% in men (P < 0.001 for each) at the conclusion of the program. Secondary
      analysis demonstrated that individuals with greater baseline levels of metabolic
      dysfunction had larger metabolic improvements, similar benefits to risk factors
      across baseline body mass index categories, and the greater the weight loss, the
      greater the metabolic benefit. CONCLUSION: Our results demonstrate that a
      worksite program targeting core behavioral skills associated with weight loss is
      an effective strategy to reduce weight and improve the components of metabolic
      syndrome amongst at-risk employees.

PMID- 26302221
TI  - Strong correlation in 1D oxygen-ion conduction of apatite-type lanthanum
      silicate.
AB  - Oxygen-ion conduction in apatite-type lanthanum silicate, La9.33+0.67x
      (SiO4)6O2+x (x = 1), has theoretically been analyzed in a first-principles manner
      followed by the nudged elastic band method and the kinetic Monte Carlo method.
      Unlike the conventional cooperative interstitialcy mechanism along the single O4
      columns, diffusing interstitial oxygen ions are frequently blocked by adjacent
      interstitial oxygen ions (Oint ions), leading to the strongly-correlated
      diffusivity and conductivity of oxygen ions in the case of chemical compositions
      with large x values. The getting-out mechanism from the O4 column is of
      importance in the long-range conduction, which temporarily transfers a part of
      Oint ions out of the columns to relax the blocking effect. The getting-out
      mechanism plays a key role also in the conduction perpendicular to the c axis (in
      the ab plane). 

PMID- 26302222
TI  - The Effect of Tear Supplementation on Ocular Surface Sensations during the
      Interblink Interval in Patients with Dry Eye.
AB  - PURPOSE: To investigate the characteristics of ocular surface sensations and
      corneal sensitivity during the interblink interval before and after tear
      supplementation in dry eye patients. METHODS: Twenty subjects (41.88+/-14.37
      years) with dry eye symptoms were included in the dry eye group. Fourteen
      subjects (39.13+/-11.27 years) without any clinical signs and/or symptoms of dry
      eye were included in the control group. Tear film dynamics was assessed by non
      invasive tear film breakup time (NI-BUT) in parallel with continuous recordings
      of ocular sensations during forced blinking. Corneal sensitivity to selective
      stimulation of corneal mechano-, cold and chemical receptors was assessed using a
      gas esthesiometer. All the measurements were made before and 5 min after saline
      and hydroxypropyl-guar (HP-guar) drops. RESULTS: In dry eye patients the
      intensity of irritation increased rapidly after the last blink during forced
      blinking, while in controls there was no alteration in the intensity during the
      first 10 sec followed by an exponential increase. Irritation scores were
      significantly higher in dry eye patients throughout the entire interblink
      interval compared to controls (p<0.004). NI-BUT significantly increased after HP
      guar (p = 0.003) but not after saline drops (p = 0.14). In both groups, either
      after saline or HP-guar the shape of symptom intensity curves remained the same
      with significantly lower irritation scores (p<0.004), however after HP-guar the
      decrease was significantly more pronounced (p<0.004). Corneal sensitivity to
      selective mechanical, cold and chemical stimulation decreased significantly in
      both groups after HP-guar (p<0.05), but not after saline drops (p>0.05).
      CONCLUSION: Ocular surface irritation responses due to tear film drying are
      considerably increased in dry eye patients compared to normal subjects. Although
      tear supplementation improves the protective tear film layer, and thus reduce
      unpleasant sensory responses, the rapid rise in discomfort is still maintained
      and might be responsible for the remaining complaints of dry eye patients despite
      the treatment.

PMID- 26302223
TI  - Evaluation of low wind modeling approaches for two tall-stack databases.
AB  - The performance of the AERMOD air dispersion model under low wind speed
      conditions, especially for applications with only one level of meteorological
      data and no direct turbulence measurements or vertical temperature gradient
      observations, is the focus of this study. The analysis documented in this paper
      addresses evaluations for low wind conditions involving tall stack releases for
      which multiple years of concurrent emissions, meteorological data, and monitoring
      data are available. AERMOD was tested on two field-study databases involving
      several SO2 monitors and hourly emissions data that had sub-hourly meteorological
      data (e.g., 10-min averages) available using several technical options: default
      mode, with various low wind speed beta options, and using the available sub
      hourly meteorological data. These field study databases included (1) Mercer
      County, a North Dakota database featuring five SO2 monitors within 10 km of the
      Dakota Gasification Company's plant and the Antelope Valley Station power plant
      in an area of both flat and elevated terrain, and (2) a flat-terrain setting
      database with four SO2 monitors within 6 km of the Gibson Generating Station in
      southwest Indiana. Both sites featured regionally representative 10-m
      meteorological databases, with no significant terrain obstacles between the
      meteorological site and the emission sources. The low wind beta options show
      improvement in model performance helping to reduce some of the over-prediction
      biases currently present in AERMOD when run with regulatory default options. The
      overall findings with the low wind speed testing on these tall stack field-study
      databases indicate that AERMOD low wind speed options have a minor effect for
      flat terrain locations, but can have a significant effect for elevated terrain
      locations. The performance of AERMOD using low wind speed options leads to
      improved consistency of meteorological conditions associated with the highest
      observed and predicted concentration events. The available sub-hourly modeling
      results using the Sub-Hourly AERMOD Run Procedure (SHARP) are relatively unbiased
      and show that this alternative approach should be seriously considered to address
      situations dominated by low-wind meander conditions. IMPLICATIONS: AERMOD was
      evaluated with two tall stack databases (in North Dakota and Indiana) in areas of
      both flat and elevated terrain. AERMOD cases included the regulatory default
      mode, low wind speed beta options, and use of the Sub-Hourly AERMOD Run Procedure
      (SHARP). The low wind beta options show improvement in model performance
      (especially in higher terrain areas), helping to reduce some of the over
      prediction biases currently present in regulatory default AERMOD. The SHARP
      results are relatively unbiased and show that this approach should be seriously
      considered to address situations dominated by low-wind meander conditions.

PMID- 26302225
TI  - End-of-Life Planning Education and Advance Directives Completion Rates.

PMID- 26302224
TI  - From "aisle" to "labile": A hierarchical National Adult Reading Test scale
      revealed by Mokken scaling.
AB  - Decline in cognitive ability is a core diagnostic criterion for dementia. Knowing
      the extent of decline requires a baseline score from which change can be
      reckoned. In the absence of prior cognitive ability scores, vocabulary-based
      cognitive tests are used to estimate premorbid cognitive ability. It is important
      that such tests are short yet informative, to maximize information and
      practicability. The National Adult Reading Test (NART) is commonly used to
      estimate premorbid intelligence. People are asked to pronounce 50 words ranging
      from easy to difficult but whether its words conform to a hierarchy is unknown.
      Five hundred eighty-seven healthy community-dwelling older people with known age
      11 IQ scores completed the NART as part of the Lothian Birth Cohort 1936 study.
      Mokken analysis was used to explore item responses for unidimensional, ordinal,
      and hierarchical scales. A strong hierarchical scale ("mini-NART") of 23 of the
      50 items was identified. These items are invariantly ordered across all ability
      levels. The validity of the interpretation of this briefer scale's score as an
      estimate of premorbid ability was examined using the actual age 11 IQ score. The
      mini-NART accounted for a similar amount of the variance in age 11 IQ as the full
      NART (NART = 46.5%, mini-NART = 44.8%). The mini-NART is proposed as a useful
      short clinical tool to estimate prior cognitive ability. The mini-NART has
      clinical relevance, comprising highly discriminatory, invariantly ordered items
      allowing for sensitive measurement, and adaptive testing, reducing test
      administration time, and patient stress.

PMID- 26302226
TI  - Metal-to-Ligand Charge-Transfer Emissions of Ruthenium(II) Pentaammine Complexes
      with Monodentate Aromatic Acceptor Ligands and Distortion Patterns of their
      Lowest Energy Triplet Excited States.
AB  - This is the first report of the 77 K triplet metal-to-ligand charge-transfer
      ((3)MLCT) emission spectra of pentaammine-MDA-ruthenium(II) ([Ru(NH3)5(MDA)](2+))
      complexes, where MDA is a monodentate aromatic ligand. The emission spectra of
      these complexes and of the related trans-[Ru(NH3)4(MDA) (MDA')](2+) complexes are
      closely related, and their emission intensities are very weak. Density functional
      theory (DFT) calculations indicate that the energies of the lowest (3)MLCT
      excited states of Ru-MDA complexes are either similar to or lower than those of
      the lowest energy metal-centered excited states ((3)MC(X(Y))), that the barrier
      to internal conversion at 77 K is large compared to kBT, and that the (3)MC(X(Y))
      excited states are weakly bound. The [Ru(NH3)5py](2+) complex is an exception to
      the general pattern: emission has been observed for the [Ru(ND3)5(d5-py)](2+)
      complex, but its lifetime is apparently very short. DFT modeling indicates that
      the excited state distortions of the different (3)MC excited states are very
      large and are in both Ru-ligand bonds along a single Cartesian axis for each
      different (3)MC excited state, nominally resulting in (3)MC(X(Y)), (3)MC((X)Y),
      and (3)MC(Z) lowest energy metal-centered states. The (3)MC(X(Y)) and (3)MC((X)Y)
      states appear to be the pseudo-Jahn-Teller distorted components of a (3)MC((XY))
      state. The (3)MC(X(Y)) states are distorted up to 0.5 A in each H3N-Ru-NH3 bond
      along a single Cartesian axis in the pentaammine and trans-tetraammine complexes,
      whereas the (3)MC(Z) states are found to be dissociative. DFT modeling of the
      (3)MLCT excited state of [Ru(NH3)5(py)](2+) indicates that the Ru center has a
      spin density of 1.24 at the (3)MLCT energy minimum and that the (3)MLCT ->
      (3)MC(Z) crossing is smooth with a very small barrier (<0.5 kcal/mol) along the
      D3N-Ru-py distortion coordinate, implying strong (3)MLCT/(3)MC excited state
      configurational mixing. Furthermore, the DFT modeling indicates that the long
      lived intermediate observed in earlier flash photolysis studies of
      [Ru(NH3)5py](2+) is a Ru(II)-(eta(2)(C?C)-py) species.

PMID- 26302227
TI  - Prevalence and patterns of chronic disease multimorbidity and associated
      determinants in Canada.
AB  - INTRODUCTION: Multimorbidity is increasingly recognized as a key issue in the
      prevention and management of chronic diseases. We examined the prevalence and
      correlates of chronic disease multimorbidity in the general adult Canadian
      population in relation to age and other key determinants. METHODS: We extracted
      data from the Canadian Community Health Survey 2011/12 on 105 416 Canadian
      adults. We analysed the data according to the number of multimorbidities (defined
      as 2+ or 3+ diseases from a list of 9) and examined the determinants of
      multimorbidity using regression analyses. RESULTS: Our findings show that 12.9%
      of Canadians report 2+ chronic diseases and 3.9% report 3+ chronic diseases.
      Those reporting 3 or more chronic diseases were more likely to be female, older,
      living in the lowest income quintile and to have not completed high school. In
      the overall population, social deprivation is associated with a 3.7 odds of
      multimorbidity, but when examined across age groups, the odds of multimorbidity
      were notably higher in middle age, 7.5 for those aged 35 to 49 years and 5.4 for
      those aged 50 to 64 years. DISCUSSION: As the proportion of Canadians living with
      multiple chronic diseases increases, we need to assess chronic disease from a
      holistic perspective that captures multimorbidity and upstream factors, to
      facilitate broader and more context-appropriate associations with healthy living,
      quality of life, health care costs and mortality. Special consideration should be
      given to the role that social deprivation plays in the development of
      multimorbidity. Canadians living in the lowest socioeconomic group are not only
      more likely to develop multimorbidity, but the onset of multimorbidity is also
      likely to be significantly earlier.

PMID- 26302228
TI  - Report Summary--Mental Illness in Canada, 2015.
AB  - This report, Mental Illness in Canada, 2015 is the first publication to include
      administrative health data from the Canadian Chronic Disease Surveillance System
      (CCDSS) for the national surveillance of mental illness. It features the most
      recent CCDSS data available (fiscal year 2009/10), as well as trend data spanning
      over a decade (1996/97 to 2009/10). It is also the first national report to
      include children and adolescents under the age of 15 years. The data presented
      within this report and subsequent updates can be accessed via the Public Health
      Agency of Canada's Chronic Disease Infobase Data Cubes at www.infobase.phac
      aspc.gc.ca. Data Cubes are interactive databases that allow users to create
      tables and graphs quickly using their Web browser. 

PMID- 26302229
TI  - Understanding Conflicting Neuropathological Findings in Patients Clinically
      Diagnosed as Having Alzheimer Dementia.

PMID- 26302230
TI  - Known and unexpected constraints evoke different kinematic, muscle, and motor
      cortical neuron responses during locomotion.
AB  - During navigation through complex natural environments, people and animals must
      adapt their movements when the environment changes. The neural mechanisms of such
      adaptations are poorly understood, especially with respect to constraints that
      are unexpected and must be adapted to quickly. In this study, we recorded
      forelimb-related kinematics, muscle activity, and the activity of motor cortical
      neurons in cats walking along a raised horizontal ladder, a complex locomotion
      task requiring accurate limb placement. One of the crosspieces was motorized, and
      displaced before the cat stepped on the ladder or at different points along the
      cat's progression over the ladder, either towards or away from the cat. We found
      that, when the crosspiece was displaced before the cat stepped onto the ladder,
      the kinematic modifications were complex and involved all forelimb joints. When
      the crosspiece displaced unexpectedly while the cat was on the ladder, the
      kinematic modifications were minimalistic and primarily involved distal joints.
      The activity of M. triceps and M. extensor digitorum communis differed based on
      the direction of displacement. Out of 151 neurons tested, 69% responded to at
      least one condition; however, neurons were significantly more likely to respond
      when crosspiece displacement was unexpected. Most often they responded during the
      swing phase. These results suggest that different neural mechanisms and motor
      control strategies are used to overcome constraints for locomotor movements
      depending on whether they are known or emerge unexpectedly. 

PMID- 26302231
TI  - Fractionation of Selenium during Selenate Reduction by Granular Zerovalent Iron.
AB  - Batch experiments were conducted using granular zerovalent iron (G-ZVI) with
      either ultrapure water or CaCO3 saturated simulated groundwater to assess the
      extent of Se isotope fractionation in solution under the anaerobic conditions
      characteristic of many aquifers. G-ZVI is a common remediation material in
      permeable reactive barriers (PRB) to treat Se-contaminated groundwater, and
      stable isotopes are a potential tool for assessing removal mechanisms. The
      solution composition, speciation of Se, and Se isotope ratios were determined
      during both sets of experiments. Dissolved Se concentrations decreased from 10 to
      <2 mg L(-1) after 3 d in the CaCO3 system and below 0.4 mg L(-1) after 2 d in the
      ultrapure water system. XANES analysis of the solid phase showed spectra
      consistent with the formation of Se(IV), Fe2(SeO3)3, FeSe, FeSe2, and Se(0) on
      the G-ZVI. Selenium isotope ratio measurements in solution in the CaCO3 and
      ultrapure water experiments showed enrichment of delta(82/76)Se values from -0.94
      +/- 0.070/00 and -1.93 +/- 0.200/00 to maximum values of 6.85 +/- 0.520/00 and
      5.68 +/- 0.200/00 over 72 and 36 h, respectively. The effective fractionations
      associated with the reduction of Se(VI) were 4.30/00 within the CaCO3 saturated
      water and 3.00/00 in ultrapure water.

PMID- 26302232
TI  - Co-delivery of platinum drug and siNotch1 with micelleplex for enhanced
      hepatocellular carcinoma therapy.
AB  - As part of HCC tumor cellularity, cancer stem cells (CSCs) are considered a major
      obstacle to eradicate hepatocellular carcinoma (HCC), which is the third most
      common cause of cancer-related death worldwide, and the accumulation of
      chemotherapeutic drug-resistant CSCs invariably accounts for poor prognosis and
      HCC relapse. In the present study, we explored the efficacy of co-delivery of
      platinum drug and siRNA targeting Notch1 to treat CSCs-harboring HCC. To overcome
      the challenging obstacles of platinum drug and siRNA in the systemic
      administration, we developed a micellar nanoparticle (MNP) to deliver
      platinum(IV) prodrug and siNotch1, hereafter referred to as (Pt(IV))MNP/siNotch1.
      We demonstrated that (Pt(IV))MNP/siNotch1 was able to efficiently deliver two
      drugs into both non-CSCs and CSCs of SMMC7721, a HCC cell line. We further found
      that siRNA-mediated inhibition of Notch1 suppression can increase the sensitivity
      of HCC cells to platinum drugs and decrease the percentage of HCC CSCs, and
      consequently resulting in enhanced proliferation inhibition and apoptosis
      induction in HCC cells in vitro. Moreover, our results indicated that the
      combined drug delivery system can remarkably augment drug enrichment in tumor
      tissues, substantially suppressing the tumor growth while avoiding the
      accumulation of CSCs in a synergistic manner in the SMMC7721 xenograft model. 

PMID- 26302233
TI  - Low cost industrial production of coagulation factor IX bioencapsulated in
      lettuce cells for oral tolerance induction in hemophilia B.
AB  - Antibodies (inhibitors) developed by hemophilia B patients against coagulation
      factor IX (FIX) are challenging to eliminate because of anaphylaxis or nephrotic
      syndrome after continued infusion. To address this urgent unmet medical need, FIX
      fused with a transmucosal carrier (CTB) was produced in a commercial lettuce
      (Simpson Elite) cultivar using species specific chloroplast vectors regulated by
      endogenous psbA sequences. CTB-FIX (~1 mg/g) in lyophilized cells was stable with
      proper folding, disulfide bonds and pentamer assembly when stored ~2 years at
      ambient temperature. Feeding lettuce cells to hemophilia B mice delivered CTB-FIX
      efficiently to the gut immune system, induced LAP(+) regulatory T cells and
      suppressed inhibitor/IgE formation and anaphylaxis against FIX. Lyophilized cells
      enabled 10-fold dose escalation studies and successful induction of oral
      tolerance was observed in all tested doses. Induction of tolerance in such a
      broad dose range should enable oral delivery to patients of different age groups
      and diverse genetic background. Using Fraunhofer cGMP hydroponic system, ~870 kg
      fresh or 43.5 kg dry weight can be harvested per 1000 ft(2) per annum yielding
      24,000-36,000 doses for 20-kg pediatric patients, enabling first commercial
      development of an oral drug, addressing prohibitively expensive purification,
      cold storage/transportation and short shelf life of current protein drugs. 

PMID- 26302235
TI  - Prospective diagnostic accuracy evaluation and clinical utilization of a modified
      assay for platelet-associated immunoglobulin in thrombocytopenic and
      nonthrombocytopenic dogs.
AB  - BACKGROUND: No diagnostic tests reliably distinguish primary immune-mediated
      thrombocytopenia (pIMT) from other causes of thrombocytopenia. OBJECTIVES: The
      purpose of the study was to evaluate diagnostic sensitivity and specificity using
      modified direct and indirect platelet-associated immunoglobulin (PAIg) assays and
      reticulated platelets (RP) by flow cytometry for the classification of
      thrombocytopenic dogs and differentiating pIMT. METHODS: Platelets were isolated
      from plasma samples of thrombocytopenic dogs and nonthrombocytopenic healthy and
      ill dogs. For direct PAIg, they were analyzed by flow cytometry after incubation
      with anti-human amylase fluorescein isothiocyanate (FITC, negative control), anti
      canine IgG-FITC, anti-canine IgM-FITC, and anti-human CD61-conjugated
      fluorochrome (AF647). For indirect PAIg, platelets from normothrombocytic dogs
      were incubated with thrombocytopenic dog plasma and analyzed similar to direct
      PAIg. RP percentages were determined based on forward light scatter vs thiazole
      orange fluorescence. RESULTS: Seventy-five thrombocytopenic dogs, 16
      nonthrombocytopenic ill dogs, and 24 healthy dogs were evaluated. Diagnostic
      sensitivity and specificity utilizing direct IgG was 29.4% and 75.9%,
      respectively; when combining direct/indirect assays (IgG/IgM), it was 76.5% and
      65.5%, respectively, for distinguishing pIMT. For RP, no significant difference
      between pIMT and sIMT was noted. RP > 8% with positive PAIg had a sensitivity of
      94% and specificity of 27.6% for distinguishing pIMT. There was a significant
      difference in platelet concentration and CD61% staining between control and pIMT.
      CONCLUSIONS: The combined modified assays resulted in fair diagnostic sensitivity
      and specificity for the diagnosis of pIMT. The modification of the immunoglobulin
      assays improved diagnostic accuracy; however, a single panel to accurately
      classify thrombocytopenia remains elusive.

PMID- 26302234
TI  - Enhanced efficiency of genetic programming toward cardiomyocyte creation through
      topographical cues.
AB  - Generation of de novo cardiomyocytes through viral over-expression of key
      transcription factors represents a highly promising strategy for cardiac muscle
      tissue regeneration. Although the feasibility of cell reprogramming has been
      proven possible both in vitro and in vivo, the efficiency of the process remains
      extremely low. Here, we report a chemical-free technique in which topographical
      cues, more specifically parallel microgrooves, enhance the directed
      differentiation of cardiac progenitors into cardiomyocyte-like cells. Using a
      lentivirus-mediated direct reprogramming strategy for expression of Myocardin,
      Tbx5, and Mef2c, we showed that the microgrooved substrate provokes an increase
      in histone H3 acetylation (AcH3), known to be a permissive environment for
      reprogramming by "stemness" factors, as well as stimulation of myocardin
      sumoylation, a post-translational modification essential to the transcriptional
      function of this key co-activator. These biochemical effects mimicked those of a
      pharmacological histone deacetylase inhibitor, valproic acid (VPA), and like VPA
      markedly augmented the expression of cardiomyocyte-specific proteins by the
      genetically engineered cells. No instructive effect was seen in cells
      unresponsive to VPA. In addition, the anisotropy resulting from parallel
      microgrooves induced cellular alignment, mimicking the native ventricular
      myocardium and augmenting sarcomere organization. 

PMID- 26302237
TI  - Naevus spilus-type congenital melanocytic naevus associated with a novel NRAS
      codon 61 mutation.

PMID- 26302236
TI  - Inter-grader Agreement of the Ocular Staining Score in the Sjogren's
      International Clinical Collaborative Alliance (SICCA) Registry.
AB  - PURPOSE: To determine the intra-observer and inter-observer reliability of a
      novel ocular staining score among trained ophthalmologists. DESIGN: Reliability
      analysis within a prospective, observational, multicenter cohort study. METHODS:
      Those enrolled in the National Institutes of Health-funded Sjogren's
      International Collaborative Clinical Alliance (SICCA) who presented for follow-up
      at the University of California San Francisco, Aravind Eye Hospital, Johns
      Hopkins University, and the University of Pennsylvania were included. Study
      participants were graded using the ocular staining score by at least 2 masked
      SICCA-trained ophthalmologists. The primary outcome for this study was the
      intraclass correlation coefficient (ICC) for the total ocular staining score.
      ICCs were also calculated for tear break-up time (TBUT) and conjunctival and
      corneal staining. RESULTS: Total ocular staining score had an ICC of 0.91 for the
      right eye (95% confidence interval [CI] 0.85-0.96) and 0.90 for the left eye (95%
      CI 0.83-0.97). Corneal staining (right eye 0.86, 95% CI 0.76-0.93, left eye 0.90,
      95% CI 0.81-0.95) and conjunctival staining (right eye 0.87, 95% CI 0.80-0.93,
      left eye 0.85, 95% CI 0.75-0.93) demonstrated excellent agreement. The ICC for
      TBUT was slightly lower (right eye 0.77, 95% CI 0.64-0.89; left eye 0.81, 95% CI
      0.68-0.90). CONCLUSIONS: Previous studies have shown that the ocular staining
      score is correlated with other diagnostic components of Sjogren syndrome. In this
      study, we demonstrate high reliability in grading among trained ophthalmologists,
      completing the validation of this test.

PMID- 26302238
TI  - Acquisition of 3D temperature distributions in fluid flow using proton resonance
      frequency thermometry.
AB  - PURPOSE: Proton resonance frequency thermometry is well established for
      monitoring small temperature changes in tissue. Application of the technique to
      the measurement of complex temperature distributions within fluid flow is of
      great interest to the engineering community and could also have medical
      applications. This work presents an experimental approach to reliably measure
      three-dimensional (3D) temperature fields in fluid flow using proton resonance
      frequency thermometry. METHODS: A velocity-compensated three-dimensional gradient
      echo sequence was used. A flexible pumping system was attached to an MR
      compatible double pipe heat exchanger. The temperature of two separate flow
      circuits could be adjusted to produce various three-dimensional spatial
      temperature distributions within the fluid flow. Validation was performed using
      MR compatible temperature probes in a uniformly heated flow. A comparative study
      was conducted with thermocouples in the presence of a spatially varying
      temperature distribution. RESULTS: In uniformly heated flow, temperature changes
      were accurately measured to within 0.5 K using proton resonance frequency
      thermometry, while spatially varying temperature changes measured with MR showed
      good qualitative agreement with pointwise measurements using thermocouples.
      CONCLUSION: Proton resonance frequency thermometry can be used in a variety of
      complex flow situations to address medical as well as engineering questions. This
      work makes it possible to gain new insights into fundamental heat transfer
      phenomena. Magn Reson Med 76:145-155, 2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 26302239
TI  - On the restricted mean survival time curve in survival analysis.
AB  - For a study with an event time as the endpoint, its survival function contains
      all the information regarding the temporal, stochastic profile of this outcome
      variable. The survival probability at a specific time point, say t, however, does
      not transparently capture the temporal profile of this endpoint up to t. An
      alternative is to use the restricted mean survival time (RMST) at time t to
      summarize the profile. The RMST is the mean survival time of all subjects in the
      study population followed up to t, and is simply the area under the survival
      curve up to t. The advantages of using such a quantification over the survival
      rate have been discussed in the setting of a fixed-time analysis. In this
      article, we generalize this approach by considering a curve based on the RMST
      over time as an alternative summary to the survival function. Inference, for
      instance, based on simultaneous confidence bands for a single RMST curve and also
      the difference between two RMST curves are proposed. The latter is informative
      for evaluating two groups under an equivalence or noninferiority setting, and
      quantifies the difference of two groups in a time scale. The proposal is
      illustrated with the data from two clinical trials, one from oncology and the
      other from cardiology. 

PMID- 26302240
TI  - Enhancement of the Stability of Fluorine Atoms on Defective Graphene and at
      Graphene/Fluorographene Interface.
AB  - Fluorinated graphene is one of the most important derivatives of graphene and has
      been found to have great potential in optoelectronic and photonic nanodevices.
      However, the stability of F atoms on fluorinated graphene under different
      conditions, which is essential to maintain the desired properties of fluorinated
      graphene, is still unclear. In this work, we investigate the diffusion of F atoms
      on pristine graphene, graphene with defects, and at graphene/fluorographene
      interfaces by using density functional theory calculations. We find that an
      isolated F atom diffuses easily on graphene, but those F atoms can be localized
      by inducing vacancies or absorbates in graphene and by creating
      graphene/fluorographene interfaces, which would strengthen the binding energy of
      F atoms on graphene and increase the diffusion energy barrier of F atoms
      remarkably. 

PMID- 26302241
TI  - Low-Dose Aspirin or Nonsteroidal Anti-inflammatory Drug Use and Colorectal Cancer
      Risk: A Population-Based, Case-Control Study.
AB  - BACKGROUND: A recent comprehensive review concluded that additional research is
      needed to determine the optimal use of aspirin for cancer prevention. OBJECTIVE:
      To assess associations between the use of low-dose aspirin or other nonsteroidal
      anti-inflammatory drugs (NSAIDs) and colorectal cancer risk. DESIGN: Population
      based, case-control study. SETTING: Northern Denmark. PATIENTS: Patients with
      first-time colorectal cancer in northern Denmark between 1994 and 2011.
      Population control participants were selected by risk set sampling. MEASUREMENTS:
      Data on drug use, comorbid conditions, and history of colonoscopy were obtained
      from prescription and patient registries. Use of low-dose aspirin (75 to 150 mg)
      and nonaspirin NSAIDs was defined according to type, estimated dose, duration,
      and consistency of use. RESULTS: Among 10 280 case patients and 102 800 control
      participants, the adjusted odds ratios (ORs) for colorectal cancer associated
      with ever use (>=2 prescriptions) of low-dose aspirin and nonaspirin NSAIDs were
      1.03 (95% CI, 0.98 to 1.09) and 0.94 (CI, 0.90 to 0.98), respectively. Continuous
      long-term use (>=5 years) of low-dose aspirin was associated with a 27% reduction
      in colorectal cancer risk (OR, 0.73 [CI, 0.54 to 0.99]), whereas the overall OR
      for cumulative long-term use (continuous or noncontinuous) was close to unity.
      Nonaspirin NSAID use was associated with a substantial reduction in colorectal
      cancer risk, particularly for long-term, high-intensity use (average defined
      daily dose >=0.3) of agents with high cyclooxygenase-2 selectivity (OR, 0.57 [CI,
      0.44 to 0.74]). LIMITATIONS: Data were unavailable on over-the-counter purchases
      of high-dose aspirin and low-dose ibuprofen or NSAID dosing schedules, there were
      several comparisons, and the authors were unable to adjust for confounding by
      some risk factors. CONCLUSION: Long-term, continuous use of low-dose aspirin and
      long-term use of nonaspirin NSAIDs were associated with reduced colorectal cancer
      risk. Persons who continuously used low-dose aspirin comprised only a small
      proportion of the low-dose aspirin users. PRIMARY FUNDING SOURCE: Danish Cancer
      Society, Aarhus University Research Foundation.

PMID- 26302242
TI  - Accuracy of Probabilistic Linkage Using the Enhanced Matching System for Public
      Health and Epidemiological Studies.
AB  - BACKGROUND: The Enhanced Matching System (EMS) is a probabilistic record linkage
      program developed by the tuberculosis section at Public Health England to match
      data for individuals across two datasets. This paper outlines how EMS works and
      investigates its accuracy for linkage across public health datasets. METHODS: EMS
      is a configurable Microsoft SQL Server database program. To examine the accuracy
      of EMS, two public health databases were matched using National Health Service
      (NHS) numbers as a gold standard unique identifier. Probabilistic linkage was
      then performed on the same two datasets without inclusion of NHS number.
      Sensitivity analyses were carried out to examine the effect of varying matching
      process parameters. RESULTS: Exact matching using NHS number between two datasets
      (containing 5931 and 1759 records) identified 1071 matched pairs. EMS
      probabilistic linkage identified 1068 record pairs. The sensitivity of
      probabilistic linkage was calculated as 99.5% (95%CI: 98.9, 99.8), specificity
      100.0% (95%CI: 99.9, 100.0), positive predictive value 99.8% (95%CI: 99.3,
      100.0), and negative predictive value 99.9% (95%CI: 99.8, 100.0). Probabilistic
      matching was most accurate when including address variables and using the
      automatically generated threshold for determining links with manual review.
      CONCLUSION: With the establishment of national electronic datasets across health
      and social care, EMS enables previously unanswerable research questions to be
      tackled with confidence in the accuracy of the linkage process. In scenarios
      where a small sample is being matched into a very large database (such as
      national records of hospital attendance) then, compared to results presented in
      this analysis, the positive predictive value or sensitivity may drop according to
      the prevalence of matches between databases. Despite this possible limitation,
      probabilistic linkage has great potential to be used where exact matching using a
      common identifier is not possible, including in low-income settings, and for
      vulnerable groups such as homeless populations, where the absence of unique
      identifiers and lower data quality has historically hindered the ability to
      identify individuals across datasets.

PMID- 26302243
TI  - Dynamics and Energy Contributions for Transport of Unfolded Pertactin through a
      Protein Nanopore.
AB  - To evaluate the physical parameters governing translocation of an unfolded
      protein across a lipid bilayer, we studied protein transport through aerolysin, a
      passive protein channel, at the single-molecule level. The protein model used was
      the passenger domain of pertactin, an autotransporter virulence protein.
      Transport of pertactin through the aerolysin nanopore was detected as transient
      partial current blockades as the unfolded protein partially occluded the
      aerolysin channel. We compared the dynamics of entry and transport for unfolded
      pertactin and a covalent end-to-end dimer of the same protein. For both the
      monomer and the dimer, the event frequency of current blockades increased
      exponentially with the applied voltage, while the duration of each event
      decreased exponentially as a function of the electrical potential. The blockade
      time was twice as long for the dimer as for the monomer. The calculated
      activation free energy includes a main enthalpic component that we attribute to
      electrostatic interactions between pertactin and the aerolysin nanopore (despite
      the low Debye length), plus an entropic component due to confinement of the
      unfolded chain within the narrow pore. Comparing our experimental results to
      previous studies and theory suggests that unfolded proteins cross the membrane by
      passing through the nanopore in a somewhat compact conformation according to the
      "blob" model of Daoud and de Gennes. 

PMID- 26302244
TI  - Proteomic Evidence for Components of Spider Silk Synthesis from Black Widow Silk
      Glands and Fibers.
AB  - Spider silk research has largely focused on spidroins, proteins that are the
      primary components of spider silk fibers. Although a number of spidroins have
      been characterized, other types of proteins associated with silk synthesis are
      virtually unknown. Previous analyses of tissue-specific RNA-seq libraries
      identified 647 predicted genes that were differentially expressed in silk glands
      of the Western black widow, Latrodectus hesperus. Only ~5% of these silk-gland
      specific transcripts (SSTs) encode spidroins; although the remaining predicted
      genes presumably encode other proteins associated with silk production, this is
      mostly unverified. Here, we used proteomic analysis of multiple silk glands and
      dragline silk fiber to investigate the translation of the differentially
      expressed genes. We find 48 proteins encoded by the differentially expressed
      transcripts in L. hesperus major ampullate, minor ampullate, and tubuliform silk
      glands and detect 17 SST encoded proteins in major ampullate silk fibers. The
      observed proteins include known silk-related proteins, but most are
      uncharacterized, with no annotation. These unannotated proteins likely include
      novel silk-associated proteins. Major and minor ampullate glands have the highest
      overlap of identified proteins, consistent with their shared, distinctive
      ampullate shape and the overlapping functions of major and minor ampullate silks.
      Our study substantiates and prioritizes predictions from differential expression
      analysis of spider silk gland transcriptomes. 

PMID- 26302246
TI  - Attention Wins over Sensory Attenuation in a Sound Detection Task.
AB  - 'Sensory attenuation', i.e., reduced neural responses to self-induced compared to
      externally generated stimuli, is a well-established phenomenon. However, very few
      studies directly compared sensory attenuation with attention effect, which leads
      to increased neural responses. In this study, we brought sensory attenuation and
      attention together in a behavioural auditory detection task, where both effects
      were quantitatively measured and compared. The classic auditory attention effect
      of facilitating detection performance was replicated. When attention and sensory
      attenuation were both present, attentional facilitation decreased but remained
      significant. The results are discussed in the light of current theories of
      sensory attenuation. 

PMID- 26302247
TI  - Isolation and Reactivity of 1,4,2-Diazaborole.
AB  - An isolable 1,4,2-diazaborole derivative was synthesized and structurally
      characterized. X-ray diffraction analysis and computational studies revealed a
      delocalization of 6pi-electrons over the BC2N2 five-membered ring, which thus
      indicates the aromatic property. The reactivity toward electrophiles such as
      MeOTf and selectfluor was also investigated. 

PMID- 26302245
TI  - Phosphotyrosine Substrate Sequence Motifs for Dual Specificity Phosphatases.
AB  - Protein tyrosine phosphatases dephosphorylate tyrosine residues of proteins,
      whereas, dual specificity phosphatases (DUSPs) are a subgroup of protein tyrosine
      phosphatases that dephosphorylate not only Tyr(P) residue, but also the Ser(P)
      and Thr(P) residues of proteins. The DUSPs are linked to the regulation of many
      cellular functions and signaling pathways. Though many cellular targets of DUSPs
      are known, the relationship between catalytic activity and substrate specificity
      is poorly defined. We investigated the interactions of peptide substrates with
      select DUSPs of four types: MAP kinases (DUSP1 and DUSP7), atypical (DUSP3,
      DUSP14, DUSP22 and DUSP27), viral (variola VH1), and Cdc25 (A-C). Phosphatase
      recognition sites were experimentally determined by measuring dephosphorylation
      of 6,218 microarrayed Tyr(P) peptides representing confirmed and theoretical
      phosphorylation motifs from the cellular proteome. A broad continuum of
      dephosphorylation was observed across the microarrayed peptide substrates for all
      phosphatases, suggesting a complex relationship between substrate sequence
      recognition and optimal activity. Further analysis of peptide dephosphorylation
      by hierarchical clustering indicated that DUSPs could be organized by substrate
      sequence motifs, and peptide-specificities by phylogenetic relationships among
      the catalytic domains. The most highly dephosphorylated peptides represented
      proteins from 29 cell-signaling pathways, greatly expanding the list of potential
      targets of DUSPs. These newly identified DUSP substrates will be important for
      examining structure-activity relationships with physiologically relevant targets.

PMID- 26302248
TI  - Meta-analysis of dropout from cognitive behavioral therapy: Magnitude, timing,
      and moderators.
AB  - In this era of insistence on evidence-based treatments, cognitive behavioral
      therapy (CBT) has emerged as a highly preferred choice for a spectrum of
      psychological disorders. Yet, it is by no means immune to some of the vagaries of
      client participation. Special concerns arise when clients drop out from
      treatment. OBJECTIVE: The aim of this study was to answer questions about the
      rate and timing of dropout from CBT, with specific reference to pretreatment
      versus during treatment phases. Also explored were several moderators of dropout.
      METHOD: A meta-analysis was performed on dropout data from 115 primary empirical
      studies involving 20,995 participants receiving CBT for a range of mental health
      disorders. RESULTS: Average weighted dropout rate was 15.9% at pretreatment, and
      26.2% during treatment. Dropout was significantly associated with (a) diagnosis,
      with depression having the highest attrition rate; (b) format of treatment
      delivery, with e-therapy having the highest rates; (c) treatment setting, with
      fewer inpatient than outpatient dropouts; and (d) number of sessions, with
      treatment starters showing significantly reduced dropout as number of sessions
      increased. Dropout was not significantly associated with client type (adults or
      adolescents), therapist licensure status, study design (randomized control trial
      [RCT] vs. non-RCT), or publication recency. CONCLUSIONS: Findings are interpreted
      with reference to other reviews. Possible clinical applications include careful
      choice and supplementing of treatment setting/delivery according to the
      diagnosis, and use of preparatory strategies. Suggestions for future research
      include standardization of operational definitions of dropout, specification of
      timing of dropout, and exploration of additional moderator variables.

PMID- 26302249
TI  - Mindfulness-based cognitive therapy (MBCT) reduces the association between
      depressive symptoms and suicidal cognitions in patients with a history of
      suicidal depression.
AB  - OBJECTIVE: In patients with a history of suicidal depression, recurrence of
      depressive symptoms can easily reactivate suicidal thinking. In this study, we
      investigated whether training in mindfulness, which is aimed at helping patients
      "decenter" from negative thinking, could help weaken the link between depressive
      symptoms and suicidal cognitions. METHOD: Analyses were based on data from a
      recent randomized controlled trial, in which previously suicidal patients were
      allocated to mindfulness-based cognitive therapy (MBCT), an active control
      treatment, cognitive psychoeducation (CPE), which did not include any meditation
      practice, or treatment as usual (TAU). After the end of the treatment phase, we
      compared the associations between depressive symptoms, as assessed through self
      reports on the Beck Depression Inventory-II (Beck, Steer, & Brown, 1996), and
      suicidal thinking, as assessed through the Suicidal Cognitions Scale (Rudd et
      al., 2001). RESULTS: In patients with minimal to moderate symptoms at the time of
      assessment, comparisons of the correlations between depressive symptoms and
      suicidal cognitions showed significant differences between the groups. Although
      suicidal cognitions were significantly related to levels of symptoms in the 2
      control groups, there was no such relation in the MBCT group. CONCLUSION: The
      findings suggest that, in patients with a history of suicidal depression,
      training in mindfulness can help to weaken the association between depressive
      symptoms and suicidal thinking, and thus reduce an important vulnerability for
      relapse to suicidal depression.

PMID- 26302250
TI  - A family-based intervention for improving children's emotional problems through
      effects on maternal depressive symptoms.
AB  - OBJECTIVE: This study focused on whether a brief family-based intervention for
      toddlers, the Family Check-Up (FCU), designed to address parent management skills
      and prevent early conduct problems, would have collateral effects on maternal
      depressive symptoms and subsequent child emotional problems. METHOD: Parents with
      toddlers were recruited from the Women, Infants, and Children Nutritional
      Supplement Program based on the presence of socioeconomic, family, and child risk
      (N = 731). Families were randomly assigned to the FCU intervention or control
      group with yearly assessments beginning at child age 2. Maternal depressive
      symptoms were measured using the Center for Epidemiological Studies Depression
      Scale at child ages 2 and 3. Child internalizing problems were collected from
      primary caregivers, alternative caregivers, and teachers using the Child Behavior
      Checklist at ages 7.5 and 8.5. RESULTS: Structural equation models revealed that
      mothers in families randomly assigned to the FCU showed lower levels of
      depressive symptoms at child age 3, which in turn were related to lower levels of
      child depressed/withdrawal symptoms as reported by primary caregivers,
      alternative caregivers, and teacher at ages 7.5-8.5. CONCLUSIONS: Findings
      suggest that a brief, preventive intervention improving maternal depressive
      symptoms can have enduring effects on child emotional problems that are
      generalizable across contexts. As there is a growing emphasis for the use of
      evidence-based and cost-efficient interventions that can be delivered in multiple
      delivery settings serving low-income families and their children, clinicians and
      researchers welcome evidence that interventions can promote change in multiple
      problem areas. The FCU appears to hold such promise.

PMID- 26302251
TI  - Bounce back: Effectiveness of an elementary school-based intervention for
      multicultural children exposed to traumatic events.
AB  - OBJECTIVE: To evaluate the feasibility and acceptability of a school-based
      intervention for diverse children exposed to a range of traumatic events, and to
      examine its effectiveness in improving symptoms of posttraumatic stress,
      depression, and anxiety. METHOD: Participants were 74 schoolchildren (Grades 1-5)
      and their primary caregivers. All participating students endorsed clinically
      significant posttraumatic stress symptoms. School clinicians were trained to
      deliver Bounce Back, a 10-session cognitive-behavioral group intervention.
      Children were randomized to immediate or delayed (3-month waitlist) intervention.
      Parent- and child-report of posttraumatic stress and depression, and child report
      of anxiety symptoms, were assessed at baseline, 3 months, and 6 months. RESULTS:
      Bounce Back was implemented with excellent clinician fidelity. Compared with
      children in the delayed condition, children who received Bounce Back immediately
      demonstrated significantly greater improvements in parent- and child-reported
      posttraumatic stress and child-reported anxiety symptoms over the 3-month
      intervention. Upon receipt of the intervention, the delayed intervention group
      demonstrated significant improvements in parent- and child-reported posttraumatic
      stress, depression, and anxiety symptoms. The immediate treatment group
      maintained or showed continued gains in all symptom domains over the 3-month
      follow-up period (6-month assessment). CONCLUSIONS: Findings support the
      feasibility, acceptability, and effectiveness of the Bounce Back intervention as
      delivered by school-based clinicians for children with traumatic stress.
      Implications are discussed.

PMID- 26302253
TI  - Improving Smallholder Farmer Biosecurity in the Mekong Region Through Change
      Management.
AB  - Transboundary animal diseases including foot-and-mouth disease and haemorrhagic
      septicaemia remain a major constraint for improving smallholder large ruminant
      productivity in the Mekong region, producing negative impacts on rural
      livelihoods and compromising efforts to reduce poverty and food insecurity. The
      traditional husbandry practices of smallholders largely exclude preventive health
      measures, increasing risks of disease transmission. Although significant efforts
      have been made to understand the social aspects of change development in
      agricultural production, attention to improving the adoption of biosecurity has
      been limited. This study reviews smallholder biosecurity risk factors identified
      in the peer-reviewed literature and from field research observations conducted in
      Cambodia and Laos during 2006-2013, considering these in the context of a change
      management perspective aimed at improving adoption of biosecurity measures.
      Motivation for change, resistance to change, knowledge management, cultural
      dimensions, systems theory and leadership are discussed. Due to geographical,
      physical and resource variability, the implementation of biosecurity
      interventions suitable for smallholders is not a 'one size fits all'.
      Smallholders should be educated in biosecurity principles and empowered to make
      personal decisions rather than adopt prescribed pre-defined interventions.
      Biosecurity interventions should be aligned with smallholder farmer motivations,
      preferably offering clear short-term risk management benefits that elicit
      interest from smallholders. Linking biosecurity and disease control with improved
      livestock productivity provides opportunities for sustainable improvements in
      livelihoods. Participatory research and extension that improves farmer knowledge
      and practices offers a pathway to elicit sustainable broad-scale social change.
      However, examples of successes need to be communicated both at the 'evidence
      based level' to influence regional policy development and at the village or
      commune level, with 'champion farmers' and 'cross-visits' used to lead local
      change. The adoption of applied change management principles to improving
      regional biosecurity may assist current efforts to control and eradicate
      transboundary diseases in the Mekong region.

PMID- 26302252
TI  - Redesigning community mental health services for urban children: Supporting
      schooling to promote mental health.
AB  - OBJECTIVE: This study examined a school- and home-based mental health service
      model, Links to Learning, focused on empirical predictors of learning as primary
      goals for services in high-poverty urban communities. METHOD: Teacher key opinion
      leaders were identified through sociometric surveys and trained, with mental
      health providers and parent advocates, on evidence-based practices to enhance
      children's learning. Teacher key opinion leaders and mental health providers
      cofacilitated professional development sessions for classroom teachers to
      disseminate 2 universal (Good Behavior Game, peer-assisted learning) and 2
      targeted (Good News Notes, Daily Report Card) interventions. Group-based and home
      based family education and support were delivered by mental health providers and
      parent advocates for children in kindergarten through 4th grade diagnosed with 1
      or more disruptive behavior disorders. Services were Medicaid-funded through 4
      social service agencies (N = 17 providers) in 7 schools (N = 136 teachers, 171
      children) in a 2 (Links to Learning vs. services as usual) * 6 (pre- and
      posttests for 3 years) longitudinal design with random assignment of schools to
      conditions. Services as usual consisted of supported referral to a nearby social
      service agency. RESULTS: Mixed effects regression models indicated significant
      positive effects of Links to Learning on mental health service use, classroom
      observations of academic engagement, teacher report of academic competence and
      social skills, and parent report of social skills. Nonsignificant between-groups
      effects were found on teacher and parent report of problem behaviors, daily
      hassles, and curriculum-based measures. Effects were strongest for young
      children, girls, and children with fewer symptoms. CONCLUSION: Community mental
      health services targeting empirical predictors of learning can improve school and
      home behavior for children living in high-poverty urban communities.

PMID- 26302254
TI  - Engineering the AAV capsid to optimize vector-host-interactions.
AB  - Adeno-associated viral (AAV) vectors are the most widely used delivery system for
      in vivo gene therapy. Vectors developed from natural AAV isolates achieved
      clinical benefit for a number of patients suffering from monogenetic disorders.
      However, high vector doses were required and the presence of pre-existing
      neutralizing antibodies precluded a number of patients from participation.
      Further challenges are related to AAV's tropism that lacks cell type selectivity
      resulting in off-target transduction. Conversely, specific cell types
      representing important targets for gene therapy like stem cells or endothelial
      cells show low permissiveness. To overcome these limitations, elegant rational
      design- as well as directed evolution-based strategies were developed to optimize
      various steps of AAV's host interaction. These efforts resulted in next
      generation vectors with enhanced capabilities, that is increased efficiency of
      cell transduction, targeted transduction of previously non-permissive cell types,
      escape from antibody neutralization and off-target free in vivo delivery of
      vector genomes. These important achievements are expected to improve current and
      pave the way towards novel AAV-based applications in gene therapy and
      regenerative medicine. 

PMID- 26302255
TI  - Source localization of an event-related potential marker of executive attention
      following mild traumatic brain injury.
AB  - Recent research suggests that intact performance on an executive attention task
      after mild traumatic brain injury (mTBI) reflects functional adaptation within
      neural networks, rather than recovery of premorbid modes of information
      processing. However, it is unclear whether this compensation includes the
      recruitment of alternative neural processing resources. The current study used
      source localization analysis to determine the location and timing of activated
      brain areas involved in the generation of an event-related potential (ERP)
      component marker of executive attention in 10 adults with mTBI and in 10 matched
      healthy controls. In both groups the cerebral sources of the late processing
      negativity component of the ERP waveform elicited during the Paced Auditory
      Serial Addition Task were localized to the left ventrolateral prefrontal cortex
      and right dorsal anterior cingulate cortex. Timing of the dipole moments was
      consistent with previous reports of the relative contributions of subregions of
      the frontal cortex critically involved in aspects of executive attention control.
      Finally, whereas abnormal intensity of ERP activation has recently been related
      to the achievement of normal levels of performance after mTBI, abnormal sources
      of cerebral activation do not appear to be a feature of the compensatory
      response.

PMID- 26302256
TI  - Colorimetric Aptasensor Based on Enzyme for the Detection of Vibrio
      parahemolyticus.
AB  - A simple colorimetric aptasensor system has been developed to detect Vibrio
      parahemolyticus. Magnetic nanoparticles (MNPs) are synthesized and conjugated
      with specific aptamers against target and used as capture probes. In addition,
      this method employs gold nanoparticles (AuNPs) as carriers of horseradish
      peroxidase (HRP) and aptamers, which served as signal probes. In the presence of
      target, a "sandwich-type" complex of AuNPs-HRP-aptamer-target-aptamer-MNPs is
      formed through specific recognition of aptamers and corresponding target. As a
      result, HRP molecules confined at the surface of the "sandwich" complexes
      catalyze the enzyme substrate, 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2 and
      generate an optical signal. Under optimal conditions, the signals are linearly
      dependent on V. parahemolyticus concentrations from 10 to 10(6) colony-forming
      units (cfu)/mL in a logarithmic plot, with a limit of detection of 10 cfu/mL.
      Owing to AuNPs, a large amount of HRP could be loaded, resulting in an amplified
      signal, and the sensitivity would be improved. This strategy has the potential of
      being extended to the construction of simple monitor systems for a variety of
      biomolecules related to food safety. 

PMID- 26302257
TI  - Dacryoadenitis associated with adenoviral keratoconjunctivitis.

PMID- 26302258
TI  - Predicting outcome in older hospital patients with delirium: a systematic
      literature review.
AB  - OBJECTIVE: Delirium is a serious neuropsychiatric syndrome common in older
      hospitalised adults. It is associated with poor outcomes, however not all people
      with delirium have poor outcomes and the risk factors for adverse outcomes within
      this group are not well described. The objective was to report which predictors
      of outcome had been reported in the literature. METHODS: We performed a
      systematic review by an initial electronic database search of MEDLINE, Embase and
      PsycINFO using four key search criteria. These were: (1) participants with a
      diagnosis of delirium, (2) clearly defined outcome measures, (3) a clearly
      defined variable as predictor of outcomes and (4) participants in the general
      hospital, rehabilitation and care home settings, excluding intensive care.
      Studies were then selected in a systematic fashion using specific predetermined
      criteria by three reviewers. RESULTS: A total of 559 articles were screened, and
      57 full text articles were assessed for eligibility. Twenty seven studies
      describing 18 different predictors of poor outcome were reported. The studies
      were rated by the Newcastle-Ottawa Score and were generally at low risk of bias.
      Four broad themes of predictor were identified; five delirium related predictors,
      two co-morbid psychiatric illness related predictors, eight patient related
      predictors and three biomarker related predictors. The most numerously described
      and clinically important appear to be the duration of the delirium episode, a
      hypoactive motor subtype, delirium severity and pre-existing psychiatric
      morbidity with dementia or depression. These are all associated with poorer
      delirium outcomes. CONCLUSION: Important predictors of poor outcomes in patients
      with delirium have been demonstrated. These could be used in clinical practice to
      focus direct management and guide discussions regarding prognosis. These results
      also demonstrate a number of key unknowns, where further research to explore
      delirium prognosis is recommended and is vital to improve understanding and
      management of this condition.

PMID- 26302259
TI  - Corrigendum.

PMID- 26302265
TI  - Multiple immunophenotypes of cardiac telocytes.
AB  - AIMS: Telocytes (TCs) form a 3-dimensional network in the myocardial
      interstitium, which most probably play important role(s) in heart development.
      However, the dynamics of their prolongations, continuous cell shape changes and
      adherence properties have not been well documented till recently. The aim of this
      study was to investigate dynamics of extension of prolongations (Telopods) and
      multiple phenotypes of cardiac TCs cultured in vitro. METHODS: Cardiac TCs were
      isolated from neonatal rats by a combined enzyme digestion process and identified
      by light microscopy, immunofluorescence analysis and scanning using electron
      microscopy (SEM). Their continuous changes in shape were analyzed by a Live Cell
      Imaging System and multiple phenotypes were identified by immunofluorescence
      analysis using various markers, like vimentin, c-kit, CD34, nanog and sca-1.
      RESULTS: Cardiac TCs displayed piriform/spindle/triangular shapes with long and
      slender telopodes showing extremely long prolongations. The morphology of cell
      body was continuously changing while their prolongations were extending
      gradually. After adhering to the surface, TCs' movement and extension of their
      prolongations lasted for approximately 1.5h. Cardiac TCs expressed mesenchymal
      cell marker vimentin, hematopoietic stem cell marker CD34, embryonic stem cell
      associated gene of Nanog, and myocardial stem cell markers sca-1 and c-kit.
      CONCLUSION: These findings indicate that cultured TCs in vitro have multiple
      phenotypes, which are most likely important for evaluating their functional roles
      in heart development.

PMID- 26302266
TI  - MiR-21 inhibits autophagy by targeting Rab11a in renal ischemia/reperfusion.
AB  - Renal ischemia-reperfusion (I/R) is one of the main causes of the acute kidney
      injury (AKI) that usually occurs during clinical surgery. Autophagy plays an
      important role in recovery from acute ischemic kidney injury. MicroRNA-21 (miR
      21) was reported to inhibit autophagy in several diseases. However, the molecular
      mechanism of miR-21 on autophagy during renal I/R is still unclear. For the in
      vitro study, NRK-52E cells were transfected with miR-21 mimics and subjected to
      I/R. Results showed that miR-21 mimics inhibited cell viability and induced cell
      apoptosis in NRK-52E cells. Expression of beclin-1 and LC3-II was induced, and
      p62 was decreased by I/R. miR-21 mimics inhibited this induction. RT-PCR and
      western blotting assay showed that miR-21 mimics inhibited the protein level of
      Rab11a, but not the mRNA level. A luciferase activity assay showed that miR-21
      directly targeted Rab11a 3'-UTR. Rab11a overexpression attenuated the effect of
      miR-21 mimics and I/R on cell viability and cell apoptosis. The expression of
      beclin-1 and LC3-II was increased, and p62 was decreased by Rab11a
      overexpression. For the in vivo assay in a rat I/R model, the miR-21 level was
      increased during renal I/R injury. Pre-treatment with miR-21 inhibitor injection
      attenuated the renal injury, and enhanced expression of LC3-II and beclin-1. The
      results showed that miR-21 inhibited autophagy by targeting Rab11a in renal I/R,
      indicating that Rab11a might be a new medical target for the treatment of renal
      I/R. 

PMID- 26302264
TI  - Pharmacology of smac mimetics; chemotype differentiation based on physical
      association with caspase regulators and cellular transport.
AB  - Cellular levels of inhibitor of apoptosis (IAP) proteins are elevated in multiple
      human cancers and their activities often play a part in promoting cancer cell
      survival by blocking apoptotic pathways, controlling signal transduction pathways
      and contributing to resistance. These proteins function through interactions of
      their BIR (baculoviral IAP repeat) protein domains with pathway components and
      these interactions are endogenously antagonized by Smac/Diablo (second
      mitochondrial activator of caspases/direct IAP binding protein with low
      isoelectric point). This report describes development of synthetic smac mimetics
      (SM) and compares their binding, antiproliferative and anti-tumor activities. All
      dimeric antagonists inhibit in vitro smac tetrapeptide binding to recombinant IAP
      proteins, rescue IAP-bound caspase-3 activity and show anti-proliferative
      activity against human A875 melanoma cells. One heterodimeric SM, SM3, binds
      tightly to IAP proteins in vitro and slowly dissociates (greater than two hours)
      from these protein complexes compared to the other antagonists. In addition, in
      vitro SM anti-proliferation potency is influenced by ABCB1 transporter (ATP
      binding cassette, sub-family B; MDR1, P-gp) activities and one antagonist, SM5,
      does not appear to be an ABCB1 efflux pump substrate. All dimeric smac mimetics
      inhibit the growth of human melanoma A875 tumors implanted in athymic mice at
      well-tolerated doses. One antagonist, SM4, shows broad spectrum in vivo anti
      tumor activity and modulates known pharmacodynamic markers of IAP antagonism.
      These data taken together demonstrate the range of diverse dimeric IAP antagonist
      activities and supports their potential as anticancer agents.

PMID- 26302267
TI  - Global increase in O-linked N-acetylglucosamine modification promotes osteoblast
      differentiation.
AB  - The balance between bone formation and bone resorption is maintained by
      osteoblasts and osteoclasts, and an imbalance in this bone metabolism leads to
      osteoporosis. Here, we found that osteoblast differentiation in MC3T3-E1 cells is
      promoted by the inactivation of O-linked beta-N-acetylglucosaminidase (O
      GlcNAcase) and suppressed by the inactivation of O-GlcNAc transferase, as
      indicated by extracellular matrix calcification. The expression of osteogenic
      genes such as alp, ocn, and bsp during osteoblast differentiation was positively
      regulated in a O-GlcNAc glycosylation-dependent manner. Because it was confirmed
      that Ets1 and Runx2 are the two key transcription factors responsible for the
      expression of these osteogenic genes, their transcriptional activity might
      therefore be regulated by O-GlcNAc glycosylation. However, osteoclast
      differentiation of RAW264 cells, as indicated by the expression and activity of
      tartrate-resistant acid phosphatase, was unaffected by the inactivation of either
      O-GlcNAcase or O-GlcNAc transferase. Our findings suggest that an approach to
      manipulate O-GlcNAc glycosylation could be useful for developing the therapeutics
      for osteoporosis.

PMID- 26302268
TI  - Experimental and Theoretical Investigations of the Bromination of Phenols with
      beta and gamma Aliphatic Substituents, including Rings.
AB  - Bromination reactions of substituted and ring fused phenols were studied by both
      experiment (t-BuNH-Br) and computation (density functional theory). The outcomes
      support each other, indicating a clear and predictable regioselective preference
      among 3,4-bis-alkylated and 3,4-ring-fused phenols. 

PMID- 26302269
TI  - Closed-cycle cold helium magic-angle spinning for sensitivity-enhanced multi
      dimensional solid-state NMR.
AB  - Magic-angle spinning (MAS) NMR is a powerful tool for studying molecular
      structure and dynamics, but suffers from its low sensitivity. Here, we developed
      a novel helium-cooling MAS NMR probe system adopting a closed-loop gas
      recirculation mechanism. In addition to the sensitivity gain due to low
      temperature, the present system has enabled highly stable MAS (vR=4-12 kHz) at
      cryogenic temperatures (T=35-120 K) for over a week without consuming helium at a
      cost for electricity of 16 kW/h. High-resolution 1D and 2D data were recorded for
      a crystalline tri-peptide sample at T=40 K and B0=16.4 T, where an order of
      magnitude of sensitivity gain was demonstrated versus room temperature
      measurement. The low-cost and long-term stable MAS strongly promotes broader
      application of the brute-force sensitivity-enhanced multi-dimensional MAS NMR, as
      well as dynamic nuclear polarization (DNP)-enhanced NMR in a temperature range
      lower than 100 K.

PMID- 26302270
TI  - Revealing the Cu(2+) ions localization at low symmetry Bi sites in
      photorefractive Bi12GeO20 crystals doped with Cu and V by high frequency EPR.
AB  - The sites of incorporation of Cu(2+) impurity ions in Bi12GeO20 single crystals
      co-doped with copper and vanadium have been investigated by electron paramagnetic
      resonance (EPR). While the X-band EPR spectra consist of a simple broad (DeltaB
      ~50 mT) line with anisotropic lineshape, the W-band EPR spectra exhibit well
      resolved, strongly anisotropic lines, due to transitions within the 3d(9)-(2)D
      ground manifold of the Cu(2+) ions. The most intense group of lines, attributed
      to the dominant Cu(2+)(I) center, displays a characteristic four components
      hyperfine structure for magnetic field orientations close to a <110> direction.
      The g and A tensor main axes are very close to one of the 12 possible sets of
      orthogonal <1-10>, <00-1> and <110> crystal directions. Several less intense
      lines, with unresolved hyperfine structure and similar symmetry properties,
      mostly overlapped by the Cu(2+)(I) spectrum, were attributed to Cu(2+)(II)
      centers. The two paramagnetic centers are identified as substitutional Cu(2+)
      ions at Bi(3+) sites with low C1 symmetry, very likely resulting from different
      configurations of neighboring charge compensating defects.

PMID- 26302271
TI  - Moving the Science Forward.
AB  - This edition of the Oncology Nursing Forum (ONF) is the "research issue" in my
      mind. That might sound strange, given that ONF is the research journal of the
      Oncology Nursing Society (ONS) and, other than the featured columns that we
      publish, all other articles are reports of research. This issue is special for
      three reasons.

PMID- 26302272
TI  - Improving Cancer Care Through Nursing Research.
AB  - Nursing research and nurse researchers have been an integral and significant part
      of the Oncology Nursing Society's (ONS's) history, as evidenced by the
      development of the Nursing Research Committee within a few years of ONS's
      establishment. Ruth McCorkle, PhD, RN, FAAN, was the committee's first
      chairperson in 1979. This was followed by the creation of the Advanced Nursing
      Research Special Interest Group in 1989 under the leadership of Jean Brown, PhD,
      RN, FAAN. ONS also began to recognize nurse researchers in 1994 by creating the
      annual ONS Distinguished Researcher Award to recognize the contributions of a
      member who has conducted or promoted research that has enhanced the science and
      practice of oncology nursing. The list of recipients and of their work is
      impressive and reflects the wide range of our practice areas (see
      http://bit.ly/1MTC5cp for the recipient list). In addition, the ONS Foundation
      began funding research in 1981 and has distributed more than $24 million in
      research grants, research fellowships, and other scholarships, lectures, public
      education projects, and career development awards (ONS Foundation, 2015). And, in
      2006, the Putting Evidence Into Practice resource was unveiled, which provides
      evidence-based intervention reviews for the 20 most common problems experienced
      by patients with cancer and their caregivers (www.ons?.org/practice
      resources/pep)?.

PMID- 26302273
TI  - The Potential Adverse Health Consequences of Exposure to Electronic Cigarettes
      and Electronic Nicotine Delivery Systems.
AB  - Tobacco continues to be the leading cause of preventable death and illness in the
      United States and the world (World Health Organization, 2011). In addition,
      tobacco is responsible for one in three cancer deaths in the United States
      (American Cancer Society, 2015). Prevention of tobacco-related disease,
      disability, and death could be achieved by promoting tobacco control (i.e.,
      preventing uptake, helping smokers quit, and protecting against exposure to
      secondhand smoke).

PMID- 26302274
TI  - Oncology Nurse Navigation Role and Qualifications.
AB  - In the early 1990s, women living in a medically underserved community acted as
      lay navigators to help other women overcome barriers to breast cancer screening
      and follow-up (Freeman, Muth, & Kerner, 1995). At that time, treatment for cancer
      was straightforward. Today, cancer treatment is complex, and understanding the
      diagnosis, treatment, and healthcare system requires the skill of an oncology
      nurse navigator (ONN). Navigation includes the entire healthcare continuum-from
      prevention, screening, diagnosis, treatment, and survivorship to end of life. The
      goal of navigation is to reduce cancer morbidity and mortality by eliminating
      barriers to timely access to cancer care, which may be financial, psychological,
      logistic, or related to communication or the healthcare delivery system.

PMID- 26302276
TI  - Mammography Screening of Chinese Immigrant Women: Ever Screened Versus Never
      Screened.
AB  - PURPOSE/OBJECTIVES: To compare the differences in mammogram completion rates over
      time between Chinese American women with and without a history of mammogram
      screening?. DESIGN: Secondary analysis of a randomized, controlled intervention
      study. SETTING: Metropolitan areas of Portland, Oregon. SAMPLE: 300 foreign-born
      Chinese immigrant women aged 40 years or older. Of these, 83 women (28%) had
      never had a mammogram. METHODS: Participants who had not been screened with a
      mammogram within the past 12 months were randomized into either an education
      group or a control (brochure) group. All participants completed a baseline
      survey, which was administered again at 3, 6, and 12 months?. MAIN RESEARCH
      VARIABLES: Mammography history, breast cancer knowledge, perceived risks,
      susceptibility, benefits, and common and cultural barriers?. FINDINGS: Women who
      had never been screened were less likely to have insurance, a regular healthcare
      provider, or to have been instructed to have a mammogram. Postintervention in the
      education group, mammogram completion was not significantly different between
      those with or without a history of screening (p = 0.52). In the control brochure
      group, significantly more women with a history of screening had a mammogram (p =
      0.03). CONCLUSIONS: Practitioners must be aware of differential effects of
      education on mammography cancer screening based on women's history of screening?.
      IMPLICATIONS FOR NURSING: Print material may not be as effective with women who
      have never been screened with a mammogram. Targeted approaches based on such
      understanding has the potential to decrease the breast cancer screening disparity
      among Chinese immigrant women?.

PMID- 26302275
TI  - The 2014-2018 Oncology Nursing Society Research Agenda.
AB  - PURPOSE/OBJECTIVES: To identify priority areas of research for the Oncology
      Nursing Society (ONS) Research Agenda for 2014-2018, consistent with ONS's
      mission to promote excellence in oncology nursing and quality cancer care?. DATA
      SOURCES: Review of the literature, 2013 ONS Research Priorities Survey, National
      Institute of Nursing Research, and the National Cancer Institute research foci?.
      DATA SYNTHESIS: Multimethod consensus-building approach by content leaders and
      content experts of the ONS Research Agenda Project Team?. CONCLUSIONS: The 2014
      2018 Research Agenda Project Team identified eight high-priority research areas:
      symptoms, late effects of cancer treatment and survivorship care, palliative and
      end-of-life care, self-management, aging, family and caregivers, improving
      healthcare systems, and risk reduction. In addition, four cross-cutting themes
      were identified: biomarkers, bioinformatics, comparative effectiveness research,
      and dissemination and implementation science. IMPLICATIONS FOR NURSING: The
      Research Agenda is a synthesis of the state of the science in cancer and
      identifies gaps and directions for the conduct and dissemination of research.
      Oncology nurses can use the agenda to inform clinical practice, develop research
      proposals, inform policy makers, support interdisciplinary research efforts, and
      promote scientist and clinician collaborations in targeted patient-centered
      research?.

PMID- 26302277
TI  - Sexuality, Menopausal Symptoms, and Quality of Life in Premenopausal Women in the
      First Year Following Hematopoietic Cell Transplantation.
AB  - PURPOSE/OBJECTIVES: To describe sexuality, menopausal symptoms, and quality of
      life (QOL) in premenopausal women in the first year following hematopoietic cell
      transplantation (HCT)?. DESIGN: One-year prospective longitudinal study. SETTING:
      Stanford University Medical Center in California.?. SAMPLE: 63 premenopausal
      female recipients of HCT with a mean age of 34.5 years. METHODS: Three
      instruments were used. MAIN RESEARCH VARIABLES: Sexuality, menopausal symptoms,
      and QOL?. FINDINGS: At one year post-HCT, women reported absent to low desire and
      arousal, adequate lubrication less than half of the time, absent or rare orgasm,
      pain during vaginal penetration more than half the time, and dissatisfaction with
      overall sex life. Women also reported moderate to severe vasomotor symptoms,
      including hot flashes, night sweats, and sweating. Twenty-one women were avoiding
      sexual activity, and 25 women were not sexually active. Mean QOL scores
      significantly increased (p = 0.028) in the first year, signifying an improvement
      in QOL. Variables predictive of improved QOL at one year post-HCT include
      decreased psychosocial and physical symptoms, sexual satisfaction, and pre-HCT
      QOL score?. CONCLUSIONS: One year post-HCT, women reported sexual dysfunction,
      sexual dissatisfaction, and menopausal symptoms, which negatively affect QOL.
      IMPLICATIONS FOR NURSING: Nurses and other healthcare providers working with
      recipients of HCT can provide anticipatory guidance on potential changes in
      sexuality and menopausal symptoms to facilitate adaptation by reducing
      discordance between expectations and new realities?.

PMID- 26302278
TI  - Fatigue and Sleep Experiences at Home in Children and Adolescents With Cancer.
AB  - PURPOSE/OBJECTIVES: To (a) investigate fatigue and sleep patterns of children and
      adolescents at home and (b) examine factors associated with fatigue and sleep..
      DESIGN: Descriptive with repeated measures?. SETTING: Homes of study participants
      in Los Angeles and Orange, California?. SAMPLE: 35 children and adolescents with
      cancer. METHODS: Data were collected using the PedsQL Multidimensional Fatigue
      Scale, which was completed once at home by each participant, and sleep
      actigraphs, which were worn for five days at home following discharge from
      hospitalization?. MAIN RESEARCH VARIABLES: General fatigue, cognitive fatigue,
      sleep-rest fatigue, sleep duration, sleep quantity, sleep efficiency, and wake
      after sleep onset?. FINDINGS: More than half of the participants had problems
      with fatigue at home. Significant correlations were found between sleep/rest
      fatigue and sleep duration. Factors that affected fatigue were age, gender, and
      cancer diagnosis. Adolescents had more problems with fatigue than children, and
      female patients had more problems with fatigue than male patients. Patients with
      sarcoma had more problems with fatigue than those with leukemia, lymphoma, and
      other cancer diagnoses. Adolescents slept less than children. CONCLUSIONS:
      Children and adolescents with cancer have fatigue and sleep problems at home that
      vary by age, gender, and cancer diagnosis?. IMPLICATIONS FOR NURSING: Data from
      the current study support the need for nurses to provide teaching about fatigue
      and sleep at home in children and adolescents with cancer. Future studies are
      needed to examine interventions that may alleviate fatigue and improve sleep at
      home?.

PMID- 26302280
TI  - The Meaning of Touch to Patients Undergoing Chemotherapy.
AB  - PURPOSE/OBJECTIVES: To explore the experience of being touched in people
      diagnosed with cancer and undergoing IV chemotherapy.? RESEARCH APPROACH:
      Qualitative, phenomenologic.? SETTING: Central New York and northern
      Pennsylvania, both in the northeastern United States?. PARTICIPANTS: 11
      Caucasian, English-speaking adults.?. METHODOLOGIC APPROACH: Individual
      interviews used open-ended questions to explore the meaning of being touched to
      each participant. Meanings of significant statements, which pertained to the
      phenomenon under investigation, were formulated hermeneutically. Themes were
      derived from immersion in the data and extraction of similar and divergent
      concepts among all interviews, yielding a multidimensional understanding of the
      meaning of being touched in this sample of participants?. FINDINGS: Participants
      verbalized awareness of and sensitivity to the regard of others who were touching
      them, including healthcare providers, family, and friends. Patients do not
      classify a provider's touch as either task or comfort oriented. Meanings evolved
      in the context of three primary themes. CONCLUSIONS: The experience of being
      touched encompasses the quality of presence of providers, family, or friends. For
      touch to be regarded as positive, patients must be regarded as inherently whole
      and equal. The quality of how touch is received is secondary to and flows from
      the relationship established between patient and provider?. INTERPRETATION: This
      study adds to the literature in its finding that the fundamental quality of the
      relationship between patient and provider establishes the perceived quality of
      touch. Previous studies have primarily divided touch into two categories.

PMID- 26302281
TI  - Breast and Colon Cancer Survivors' Expectations About Physical Activity for
      Improving Survival.
AB  - PURPOSE/OBJECTIVES: To compare physical activity outcome expectations related to
      cancer survival with traditional physical activity outcome expectations in breast
      and colon cancer survivors?. DESIGN: Cross-sectional survey?. SETTING: Canada and
      the United States. SAMPLE: 146 participants?. METHODS: Self-reported survey
      instruments and height and weight measurement. The online survey was completed
      once by each participant?. MAIN RESEARCH VARIABLES: Godin Leisure-Time Exercise
      Questionnaire, Multidimensional Outcome Expectations for Exercise Scale (MOEES),
      and an item assessing physical activity outcome expectations related to cancer
      survival. FINDINGS: Paired sample t tests indicated that the mean score for the
      physical subscale of the MOEES was significantly higher than the mean score on
      the physical activity outcome expectations related to cancer survival variable (p
      < 0.001). Multiple regression analyses indicated that physical activity outcome
      expectations related to cancer survival explained 4.8% of the variance in
      physical activity (p = 0.011)?. CONCLUSIONS: Findings from the current study
      suggest that, among breast and colon cancer survivors, outcome expectations
      related to cancer survival may influence physical activity levels and may not be
      as realized as traditional outcome expectations?. IMPLICATIONS FOR NURSING:
      Oncology nurses should familiarize themselves with the guidelines and benefits of
      physical activity for survivors so they can provide guidance and support to
      patients.

PMID- 26302282
TI  - Safeguarding the Children: The Cancer Journey of Young Mothers.
AB  - PURPOSE/OBJECTIVES: To investigate how young mothers manage their maternal roles
      and responsibilities during their journey as patients with cancer?. RESEARCH
      APPROACH: Semistructured face-to-face interviews and analysis?. SETTING: Rural
      and urban communities in eastern Canada.? PARTICIPANTS: 18 mothers aged 27-45
      years when diagnosed and who were concluding or had concluded treatment for
      breast or non-ovarian reproductive cancer. METHODOLOGIC APPROACH: Glaserian
      Grounded Theory. FINDINGS: During the various phases of the cancer journey,
      mothers focus their efforts on protecting their children from psychological harm.
      Safeguarding the Children is the explanatory model generated from the interview
      data that consists of four strategies-customizing exposure, reducing disruption
      to family life, finding new ways to be close, and increasing vigilance-which
      mothers implement to protect their children?. CONCLUSIONS: Young mothers with
      cancer manage their maternal roles and responsibilities by strategizing how they
      can mitigate threats to their children's psychological well-being?.
      INTERPRETATION: Nurses are ideally suited to address holistic needs and concerns
      of women with cancer who are mothers. Safeguarding the Children, as an
      explanatory model for practice, may equip oncology nurses with requisite
      knowledge and understanding to better anticipate resource, counseling, support,
      and referral needs of young mothers during their cancer journey?.

PMID- 26302279
TI  - Gender Differences in Predictors of Quality of Life at the Initiation of
      Radiation Therapy.
AB  - PURPOSE/OBJECTIVES: To evaluate gender differences in quality of life (QOL),
      demographic, clinical, and symptom characteristics.? DESIGN: Prospective,
      observational.? SETTING: Two radiation oncology departments in northern
      California.? SAMPLE: 185 patients before initiation of radiation therapy (RT).?
      METHODS: At their RT simulation visit, patients completed a demographic
      questionnaire, a measure of QOL, and symptom-specific scales. Backward
      elimination regression analyses were conducted to determine the significant
      predictors of QOL?. MAIN RESEARCH VARIABLES: QOL, gender, and 20 potential
      predictors?. FINDINGS: In women, depressive symptoms, functional status, age, and
      having children at home explained 64% of the variance in QOL. In men, depressive
      symptoms, state anxiety, number of comorbidities, being a member of a racial or
      ethnic minority, and age explained 70% of the variance in QOL?. CONCLUSIONS:
      Predictors of QOL differed by gender. Depressive symptom score was the greatest
      contributor to QOL in both genders.?. IMPLICATIONS FOR NURSING: Nurses need to
      assess for QOL and depression at the initiation of RT. Knowledge of the different
      predictors of QOL may be useful in the design of gender-specific interventions to
      improve QOL.

PMID- 26302284
TI  - Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
AB  - This article describes the Preferred Reporting Items of Systematic Reviews and
      Meta-Analyses (PRISMA) guidelines that are intended to help authors improve the
      reporting of systematic reviews and meta-analyses, illustrating with examples
      from the Oncology Nursing Society journals and Putting Evidence Into Practice
      resources.

PMID- 26302283
TI  - Oxidative Stress, Motor Abilities, and Behavioral Adjustment in Children Treated
      for Acute Lymphoblastic Leukemia.
AB  - PURPOSE/OBJECTIVES: To examine associations among oxidative stress, fine and
      visual-motor abilities, and behavioral adjustment in children receiving
      chemotherapy for acute lymphoblastic leukemia (ALL)?. DESIGN: A prospective,
      repeated-measures design?. SETTING: Two pediatric oncology settings in the
      southwestern United States. SAMPLE: 89 children with ALL were followed from
      diagnosis to the end of chemotherapy. METHODS: Serial cerebrospinal fluid samples
      were collected during scheduled lumbar punctures and analyzed for oxidative
      stress biomarkers. Children completed fine motor dexterity, visual processing
      speed, and visual-motor integration measures at three time points. Parents
      completed child behavior ratings at the same times. MAIN RESEARCH VARIABLES:
      Oxidative stress, fine motor dexterity, visual processing, visual-motor
      integration, and behavioral adjustment?. FINDINGS: Children with ALL had below
      average fine motor dexterity, visual processing speed, and visual-motor
      integration following the induction phase of ALL therapy. By end of therapy,
      visual processing speed normalized, and fine motor dexterity and visual-motor
      integration remained below average. Oxidative stress measures correlated with
      fine motor dexterity and visual-motor integration. Decreased motor functioning
      was associated with increased hyperactivity and anxiety?. CONCLUSIONS: Oxidative
      stress occurs following chemo-therapy for childhood ALL and is related to
      impaired fine motor skills and visual symptoms?. IMPLICATIONS FOR NURSING: Early
      intervention should be considered to prevent fine motor and visual-spatial
      deficits, as well as behavioral problems.

PMID- 26302285
TI  - Creating a Healthy Practice Environment: A Call to Action for Oncology Nurses.
AB  - When nurse researcher Marlene Kramer published Reality Shock: Why Nurses Leave
      Nursing in 1974, her seminal work launched a national discussion related to the
      distress felt by many baccalaureate-prepared novice nurses about leaving the
      academic setting and transitioning to the clinical setting. In particular, Kramer
      (1974) highlighted conflict between the values these new nurses had been taught
      in school and the reality of practicing as a professional nurse in a clinical
      setting. For example, in an educational setting, nursing students may focus on
      one or two patients at a time, whereas in the clinical setting, nurses must
      practice simultaneously with multiple patients with varied and numerous health
      deficits. This conflict is felt acutely by novice and experienced oncology nurses
      who are tasked with providing quality physical care, as well as emotional care
      and support to patients with cancer and their families?.

PMID- 26302286
TI  - Malakoplakia After Allogeneic Hematopoietic Stem Cell Transplantation.
AB  - A 32-year-old woman named A.C. was diagnosed five years ago with stage IIIB
      nodular sclerosing Hodgkin lymphoma (HL). Following initial chemotherapy, she had
      refractory disease as evidenced by hypermetabolic activity on positron-emission
      tomography (PET) scan. A.C. was treated with a short course of salvage
      chemotherapy, stem cell collection, and autologous HSCT about 11 months after
      initial diagnosis. Her post-transplantation course was complicated by pneumonia
      and interstitial lung disease secondary to chemotherapy that rapidly improved
      with high-dose steroids?.

PMID- 26302287
TI  - Pharmacogenomic Testing and Warfarin Management.
AB  - Warfarin has been used for the prevention of thrombosis for more than 50 years
      and is the most frequently prescribed vitamin K antagonist in North America (Gage
      & Eby, 2003). Its mode of action is to prevent vitamin K from converting to
      vitamin KH2, thereby inhibiting clotting factors (Johnson & Cavallari, 2015).
      Warfarin metabolism is affected by variations in the cytochrome P450 2C9 (CYP2C9)
      and the vitamin K epoxide reductase complex 1 (VKORC1) genotypes. CYP2C9 affects
      the drug's pharmacokinetics, or metabolism, whereas VKORC1, the target protein of
      warfarin, affects the drug's pharmacodynamics, or its impact on cell proteins?.

PMID- 26302288
TI  - The Challenge of Rare Cancers in Current and Advancing Treatment.
AB  - The term rare cancers is relatively new in oncology, with significant presence in
      cancer literature occurring only since the early 2000s. Epidemiologic studies in
      Europe and the United States show that rare cancers account for about 25% of
      adult cancers (Eslick, 2012). However, rare cancer types have been traditionally
      understudied, with an associated lack of progress in survival and challenges in
      decision making for patients, physicians, and policy makers (Greenlee et al.,
      2010). Initiatives led within the European Union and with the United States are
      intended to boost progress in treatment for rare cancers through collective
      research and shared databases (Keat et al., 2013). Nurses see patients with rare
      cancers struggle for access to quality, evidence-based care, as well as the
      isolation they endure as they seek the information and support needed to cope
      with the diagnosis of a life-threatening illness..

PMID- 26302290
TI  - Cardiovascular Disease Risk and Breast Cancer Outcomes: A Pilot Study.
AB  - PURPOSE/OBJECTIVES: To assess feasibility of using electronic health records for
      profiling multiple cardiovascular disease (CVD) risk factors in women with breast
      cancer at diagnosis and five years post-treatment, and to explore relationships
      among CVD risk factors and breast cancer outcomes?. DESIGN: Retrospective,
      descriptive?. SETTING: A comprehensive cancer center in the southwestern United
      States?. SAMPLE: 200 women with stage 0-III breast cancer.?. METHODS: A record
      review using an instrument to profile multiple CVD risk factors and breast cancer
      outcomes?. MAIN RESEARCH VARIABLES: CVD risk factors, such as blood pressure (BP)
      and hemoglobin A1C (HbA1C), and breast cancer outcomes, such as metastasis?.
      FINDINGS: Most data on CVD risk factors were undocumented. Even BP values to
      assess hypertension were missing in 35% of women at breast cancer diagnosis.
      Women with poor outcomes had trends toward higher blood glucose and HbA1C than
      women with good outcomes?. CONCLUSIONS: The study failed to comprehensively
      capture CVD risk factors in women with breast cancer because of missing data.
      Glucose control may be associated with breast cancer outcomes?. IMPLICATIONS FOR
      NURSING: Better documentation of shared risk factors for CVD and breast cancer is
      needed. Prospective studies are needed to evaluate shared CVD risk factors and
      breast cancer outcomes because of missing health record information?.

PMID- 26302289
TI  - Assessing Suicidal Ideation and Behaviors Among Survivors of Childhood Brain
      Tumors and Their Mothers During Sociobehavioral Research.
AB  - PURPOSE/OBJECTIVES: To describe the development and feasibility of a protocol for
      nonpsychiatric subspecialty research staff members to screen research
      participants who endorse suicidal ideations or behaviors during data collection?.
      DESIGN: Descriptive protocol development.?. SETTING: The Children's Hospital of
      Philadelphia and the University of Pennsylvania.?. SAMPLE: 186 mother caregivers
      and 134 adolescent or young adult survivors of childhood brain tumors, with the
      protocol implemented for 5 caregivers and 11 survivors. METHODS: During telephone
      and home-based interviews, the interviewer assessed the participant using the
      Columbia-Suicide Severity Rating Scale (C-SSRS). MAIN RESEARCH VARIABLES:
      Expressed suicidal ideation or behavior?. FINDINGS: Implementation of the C-SSRS
      by nonpsychiatric subspecialty staff members was feasible and valid.
      Interviewers' conclusions based on this instrument matched those of the mental
      health professional who followed up with participants. Process notes contained
      themes about the participants, including anger and sadness in survivors and the
      physical and emotional demands of the survivor in caregivers. Progress notes for
      the interviewer included a reiteration of events, whether the assessment was
      successful, and whether the recommendation of the interviewer was in agreement
      with that of the mental health professional?. CONCLUSIONS: The protocol based on
      the C-SSRS was useful and feasible for nonpsychiatric subspecialty staff members
      to use in the collection of data from survivors of childhood brain tumors and
      their caregivers. IMPLICATIONS FOR NURSING: Survivors of childhood brain tumors
      and their caregivers may experience psychosocial distress. Nurses, as research
      assistants or in other roles, can use tools such as the C-SSRS to assist in front
      line assessments. ?.

PMID- 26302291
TI  - Intracranial Melanotic Schwannomas.
AB  - STUDY AIMS: Melanotic schwannomas (MSs) are an extremely rare variant of nerve
      sheath tumor. Lesions are characterized by melanin-producing cells that resemble
      ultrastructural features of Schwann cells. The main location is the paraspinal
      thoracic region, followed by other extraneural locations such as skin, soft
      tissues, bone, and viscera. Craniofacial and intracranial lesions are extremely
      rare. They may occur either sporadically or related to familiar syndromes, such
      as neurofibromatosis type II and Carney complex, a rare multisystemic autosomal
      dominant hereditary syndrome. Despite the benign histologic appearance, these
      tumors can recur or metastasize, even after a long time. We provide an overview
      of the epidemiological, clinical, radiologic, and histopathologic characteristics
      of intracranial MSs, with particular emphasis on diagnostic and therapeutic
      strategies and related clinical outcomes. MATERIAL AND METHODS: We performed a
      literature review on MSs (1932-2012) regarding intracranial and other
      localization. An illustrative case is reported. RESULTS: To the best of our
      knowledge, 17 papers reporting 18 cases of intracranial MSs were previously
      published. All these studies are either case report or clinical series describing
      intracranial MSs. Therapeutic results and prognostic factors were reviewed.
      CONCLUSION: Radical surgical resection is considered the treatment of choice for
      MS, but treatment guidelines still do not exist. Radiotherapy seems to play an
      important role in reducing the risk of recurrence in the case of subtotal tumor
      resection. Despite the reported encouraging results, only anecdotal data are
      available in the pertinent literature. Future studies should focus on the role of
      radiotherapy as adjuvant treatment when radical surgical excision cannot be
      achieved.

PMID- 26302292
TI  - DNA single-base mismatch study using graphene oxide nanosheets-based fluorometric
      biosensors.
AB  - Single nucleotide polymorphisms (SNPs) are frequently associated with various
      gene-related human diseases, whose determination has attracted great interest.
      Herein, we report a graphene oxide (GO) nanosheets-based fluorometric DNA
      biosensor to study the type and location of the single-base mismatch, as well as
      the influence of the length of the strands. The results indicated that both short
      and long targets led to much lower fluorescence signals than the perfectly
      complementary target, while the type of mismatched base had negligible influence
      on the results. Furthermore, targets with mismatch location near the 5' end led
      to higher fluorescence intensity than those near the 3' end when the dye was
      tagged at the 5' end of the probe. 

PMID- 26302293
TI  - PSYCHOMETRIC PROPERTIES OF THE THREE PATHWAYS TO WELL-BEING SCALE IN A LARGE
      SAMPLE OF ARGENTINEAN ADOLESCENTS.
AB  - The Authentic Happiness Theory considers that well-being can be reached by three
      main pathways: a pleasant life, an engaged life, or a meaningful life. This study
      investigates the psychometric properties of the Three Pathways to Well-being
      scale in Argentinean adolescents and compares that to prior results for
      Argentinean adults. A sample of 255 Argentinean adolescent students (110 boys,
      145 girls) aged between 13 and 18 years (M age = 15.5, SD = 1.6) was used in this
      study. The participants completed the Spanish versions of the Three Pathways to
      Well-being scale, the Meaning in Life Questionnaire, the Satisfaction With Life
      Scale, and the Personal Wellbeing Index. Confirmatory factor analyses verified
      the three-factor structure of the test, accounting for 46% of the variance. The
      internal consistencies were alpha = .76 for the pleasant life, alpha = .80 for
      the engaged life, and alpha = .70 for the meaningful life. Concurrent validity
      was examined with the Satisfaction With Life Scale, the Personal Wellbeing Index,
      and the Meaning in Life Questionnaire, and the engaged life was the pathway most
      strongly associated with the positive related measures.

PMID- 26302294
TI  - RELATIONSHIPS BETWEEN IDENTITY AND ACADEMIC MOTIVATION.
AB  - This study examined university students' academic motivation, focusing on
      individual differences in their sense of identity. The participants were 109
      female Japanese students from two private universities (age range = 19-22 yr., M
      = 19.3, SD = 0.6). They completed four scales: the Multidimensional Ego Identity
      Scale, the Scale of Students' Attitude Toward Their Classes, the Academic
      Motivation Inventory, and the Scale of Lecture Self-Evaluation. Correlational
      analyses assessed the relationships between subscales. Then, path analysis was
      conducted to evaluate whether sense of identity affected attitude toward classes,
      academic motivation, and lecture self-evaluation. Differences particularly in
      psychosocial identity and self-identity accounted for significant variance in the
      students' attitudes toward classes, academic motivation, and lecture self
      evaluation.

PMID- 26302295
TI  - RELATIONSHIP BETWEEN PARENTS' MOTIVATION FOR PHYSICAL ACTIVITY AND THEIR BELIEFS,
      AND SUPPORT OF THEIR CHILDREN'S PHYSICAL ACTIVITY: A CLUSTER ANALYSIS.
AB  - Previous studies have neglected the multivariate nature of motivation. The
      purpose of the current study was to first identify motivational profiles of
      parents' own physical activity. Second, the study examined if such profiles
      differ in the way in which parents perceive their children's competence in
      physical activity and the importance and support given to their children's
      physical activity. 711 physically active parents (57% mothers; M age = 39.7 yr.;
      children 6-11 years old) completed the Situational Motivation Scale, the Parents'
      Perceptions of Physical Activity Importance and their Children's Ability
      Questionnaire, and the Parental Support for Physical Activity Scale. Cluster
      analyses indicated four motivational profiles: Highly self-determined, Moderately
      self-determined, Non-self-determined, and Externally motivated profiles. Parents'
      beliefs and support toward their children's physical activity significantly
      differed across these profiles. It is the first study using Self-Determination
      Theory that provides evidence for the interpersonal outcomes of motivation.

PMID- 26302296
TI  - YOGA AND THE INTERPLAY BETWEEN ATTENTIONAL LOAD AND EMOTION INTERFERENCE.
AB  - This study compared 45 yoga practitioners (M age = 29.7 yr., SD = 6.4) and 45
      matched controls (M age = 29.3 yr., SD = 6.2) on the performance of a behavioral
      task that assessed negative emotion interference during a high- and a low
      attentional demand condition, as well as on state and trait anxiety scores.
      Outcomes were also compared between beginner and advanced practitioners. For the
      behavioral task, the final sample comprised 36 yoga and 38 control participants.
      The yoga group presented lower emotion interference in the high attentional
      condition, compared to the low attentional condition; rated emotional images as
      less unpleasant, compared to controls; and reported lower state and trait anxiety
      scores relative to controls. Also, emotion interference in the low attentional
      condition was lower among advanced practitioners and state anxiety was lower
      among practitioners attending more than two weekly yoga classes. The results
      suggested that yoga may help improve self-regulatory skills and lower anxiety.
      The psychological mechanisms underlying the relationship between yoga and emotion
      regulation should be further investigated in longitudinal studies.

PMID- 26302297
TI  - The most incompressible metal osmium at static pressures above 750 gigapascals.
AB  - Metallic osmium (Os) is one of the most exceptional elemental materials, having,
      at ambient pressure, the highest known density and one of the highest cohesive
      energies and melting temperatures. It is also very incompressible, but its high
      pressure behaviour is not well understood because it has been studied so far only
      at pressures below 75 gigapascals. Here we report powder X-ray diffraction
      measurements on Os at multi-megabar pressures using both conventional and double
      stage diamond anvil cells, with accurate pressure determination ensured by first
      obtaining self-consistent equations of state of gold, platinum, and tungsten in
      static experiments up to 500 gigapascals. These measurements allow us to show
      that Os retains its hexagonal close-packed structure upon compression to over 770
      gigapascals. But although its molar volume monotonically decreases with pressure,
      the unit cell parameter ratio of Os exhibits anomalies at approximately 150
      gigapascals and 440 gigapascals. Dynamical mean-field theory calculations suggest
      that the former anomaly is a signature of the topological change of the Fermi
      surface for valence electrons. However, the anomaly at 440 gigapascals might be
      related to an electronic transition associated with pressure-induced interactions
      between core electrons. The ability to affect the core electrons under static
      high-pressure experimental conditions, even for incompressible metals such as Os,
      opens up opportunities to search for new states of matter under extreme
      compression. 

PMID- 26302299
TI  - The cognitive neuropsychiatry of delusional belief.
AB  - According to the 'two-factor' cognitive-neuropsychiatric approach to delusional
      belief, two factors, in combination, explain the generation and maintenance of
      monothematic delusions. The first factor varies from delusion to delusion and
      explains why a patient generates a particular implausible thought in the first
      place. The second factor explains why a patient fails to reject the implausible
      thought as belief. This two-factor approach began with a 'two-deficit' account of
      bizarre monothematic delusions, according to which bizarre delusions are
      generated when a (first-factor) deficit of basic sensory/affective processing
      fundamentally distorts perceived reality. Deficits of this type are discussed and
      contrasted with motivated attentional biases in more mundane delusions. To better
      specify the second factor, I contrast 'explanationist' and 'endorsement'
      approaches to the role of aberrant experience in delusion formation and propose a
      'received-reflective' spectrum. At one pole of this spectrum are purely received
      delusions, which arise fully formed and fully (mis)believed in consciousness as
      the (mis)perceived reality. At the other pole are purely reflective delusions,
      which arise after reflection upon a vague and disquieting experience, and for
      which the crystallization of delusional conviction is more gradual. Most
      delusions lie in between, a mix of received 'delusional seed' and reflective
      elaboration. Underpinning all monothematic delusions, wherever they might lie on
      this spectrum may be a form of 'doxastic inhibitory failure'-a difficulty with
      inhibiting a belief to reason about it as if it might not be true. I conclude by
      considering how this account might apply to polythematic delusions. WIREs Cogni
      Sci 2011 2 449-460 DOI: 10.1002/wcs.121 For further resources related to this
      article, please visit the WIREs website. 

PMID- 26302300
TI  - Hemispheric asymmetry: contributions from brain imaging.
AB  - A series of studies using functional and structural magnetic resonance imaging,
      including diffusion tensor imaging measures also, to elucidate the aspects of
      hemispheric asymmetry are reviewed. It is suggested that laterality evolved as a
      response to the demands of language and the need for air-based communication
      which may have necessitated a division of labor between the hemispheres in order
      to avoid having duplicate copies in both the hemispheres that would increase
      processing redundancy. This would have put pressure on brain structures related
      to the evolution of language and speech, such as the left peri-Sylvian region.
      MRI data are provided showing structural and functional asymmetry in this region
      of the brain and how fibers connecting the right and left peri-Sylvian regions
      pass through the corpus callosum. It is further suggested that the so-called
      Yakelovian-torque, i.e., the twisting of the brain along the longitudinal axis,
      with the right frontal and left occipital poles protruding beyond the
      corresponding left and right sides, was necessary for the expansion of the left
      peri-Sylvian region and the right occipito-parietal regions subserving the
      processing of spatial relations. Functional magnetic resonance imaging data
      related to sex differences for visuo-spatial processing are presented showing
      enhanced right-sided activation in posterior parts of the brain in both sexes,
      and frontal activation including Broca's area in the female group only,
      suggesting that males and females use different strategies when solving a
      cognitive task. The paper ends with a discussion of the role of the corpus
      callosum in laterality and the role played by structural asymmetry in
      understanding corresponding functional asymmetry. WIREs Cogni Sci 2011 2 461-478
      DOI: 10.1002/wcs.122 For further resources related to this article, please visit
      the WIREs website. 

PMID- 26302301
TI  - Psychology of auditory perception.
AB  - Audition is often treated as a 'secondary' sensory system behind vision in the
      study of cognitive science. In this review, we focus on three seemingly simple
      perceptual tasks to demonstrate the complexity of perceptual-cognitive processing
      involved in everyday audition. After providing a short overview of the
      characteristics of sound and their neural encoding, we present a description of
      the perceptual task of segregating multiple sound events that are mixed together
      in the signal reaching the ears. Then, we discuss the ability to localize the
      sound source in the environment. Finally, we provide some data and theory on how
      listeners categorize complex sounds, such as speech. In particular, we present
      research on how listeners weigh multiple acoustic cues in making a categorization
      decision. One conclusion of this review is that it is time for auditory cognitive
      science to be developed to match what has been done in vision in order for us to
      better understand how humans communicate with speech and music. WIREs Cogni Sci
      2011 2 479-489 DOI: 10.1002/wcs.123 For further resources related to this
      article, please visit the WIREs website. 

PMID- 26302298
TI  - Crystal structure of the dynamin tetramer.
AB  - The mechanochemical protein dynamin is the prototype of the dynamin superfamily
      of large GTPases, which shape and remodel membranes in diverse cellular
      processes. Dynamin forms predominantly tetramers in the cytosol, which
      oligomerize at the neck of clathrin-coated vesicles to mediate constriction and
      subsequent scission of the membrane. Previous studies have described the
      architecture of dynamin dimers, but the molecular determinants for dynamin
      assembly and its regulation have remained unclear. Here we present the crystal
      structure of the human dynamin tetramer in the nucleotide-free state. Combining
      structural data with mutational studies, oligomerization measurements and Markov
      state models of molecular dynamics simulations, we suggest a mechanism by which
      oligomerization of dynamin is linked to the release of intramolecular
      autoinhibitory interactions. We elucidate how mutations that interfere with
      tetramer formation and autoinhibition can lead to the congenital muscle disorders
      Charcot-Marie-Tooth neuropathy and centronuclear myopathy, respectively. Notably,
      the bent shape of the tetramer explains how dynamin assembles into a right-handed
      helical oligomer of defined diameter, which has direct implications for its
      function in membrane constriction. 

PMID- 26302302
TI  - Visual attention.
AB  - A typical visual scene we encounter in everyday life is complex and filled with a
      huge amount of perceptual information. The term, 'visual attention' describes a
      set of mechanisms that limit some processing to a subset of incoming stimuli.
      Attentional mechanisms shape what we see and what we can act upon. They allow for
      concurrent selection of some (preferably, relevant) information and inhibition of
      other information. This selection permits the reduction of complexity and
      informational overload. Selection can be determined both by the 'bottom-up'
      saliency of information from the environment and by the 'top-down' state and
      goals of the perceiver. Attentional effects can take the form of modulating or
      enhancing the selected information. A central role for selective attention is to
      enable the 'binding' of selected information into unified and coherent
      representations of objects in the outside world. In the overview on visual
      attention presented here we review the mechanisms and consequences of selection
      and inhibition over space and time. We examine theoretical, behavioral and
      neurophysiologic work done on visual attention. We also discuss the relations
      between attention and other cognitive processes such as automaticity and
      awareness. WIREs Cogni Sci 2011 2 503-514 DOI: 10.1002/wcs.127 For further
      resources related to this article, please visit the WIREs website. 

PMID- 26302303
TI  - Development of visual perception.
AB  - Processes of visual development that yield a view of the world as coherent and
      stable begin well before birth and extend over the first several years after the
      onset of visual experience. Infants are born capable of seeing and with specific
      preferences that guide the point of gaze to relevant portions of the visual scene
      to support learning about objects and faces. Visual development after birth is
      characterized by critical periods in many notable visual functions, and by
      extensive learning from experience and increasing control over eye movement
      systems. WIREs Cogni Sci 2011 2 515-528 DOI: 10.1002/wcs.128 For further
      resources related to this article, please visit the WIREs website. 

PMID- 26302304
TI  - Change blindness and inattentional blindness.
AB  - Change blindness and inattentional blindness are both failures of visual
      awareness. Change blindness is the failure to notice an obvious change.
      Inattentional blindness is the failure to notice the existence of an unexpected
      item. In each case, we fail to notice something that is clearly visible once we
      know to look for it. Despite similarities, each type of blindness has a unique
      background and distinct theoretical implications. Here, we discuss the central
      paradigms used to explore each phenomenon in a historical context. We also
      outline the central findings from each field and discuss their implications for
      visual perception and attention. In addition, we examine the impact of task and
      observer effects on both types of blindness as well as common pitfalls and
      confusions people make while studying these topics. WIREs Cogni Sci 2011 2 529
      546 DOI: 10.1002/wcs.130 For further resources related to this article, please
      visit the WIREs website. 

PMID- 26302305
TI  - Recursion: what is it, who has it, and how did it evolve?
AB  - Recursion is a topic of considerable controversy in linguistics, which stems from
      its varying definitions and its key features, such as its universality,
      uniqueness to human language, and evolution. Currently, there appear to be at
      least two common senses of recursion: (1) embeddedness of phrases within other
      phrases, which entails keeping track of long-distance dependencies among phrases
      and (2) the specification of the computed output string itself, including meta
      recursion, where recursion is both the recipe for an utterance and the
      overarching process that creates and executes the recipes. There are also at
      least two evolutionary scenarios for the adaptive value of recursion in human
      language. The gradualist position posits precursors, such as animal communication
      and protolanguages, and holds that the selective purpose of recursion was for
      communication. The saltationist position assumes no gradual development of
      recursion and posits that it evolved for reasons other than communication. In the
      latter view, some heritable event associated with a cognitive prerequisite of
      language, such as Theory of Mind or working memory capacity, allowed recursive
      utterances. Evolutionary adaptive reasons for recursive thoughts were also
      proffered, including diplomatic speech, perlocutionary acts, and prospective
      cognitions. WIREs Cogni Sci 2011 2 547-554 DOI: 10.1002/wcs.131 For further
      resources related to this article, please visit the WIREs website. 

PMID- 26302306
TI  - Reasoning, logic, and psychology.
AB  - We argue that reasoning has been conceptualized so narrowly in what is known as
      'psychology of reasoning' that reasoning's relevance to cognitive science has
      become well-nigh invisible. Reasoning is identified with determining whether a
      conclusion follows validly from given premises, where 'valid' is taken to mean
      'valid according to classical logic'. We show that there are other ways to
      conceptualize reasoning, more in line with current logical theorizing, which give
      it a role in psychological processes ranging from (verbal) discourse
      comprehension to (nonverbal) planning. En route we show that formal logic, at
      present marginalized in cognitive science, can be an extremely valuable modeling
      tool. In particular, there are cases in which probabilistic modeling must fail,
      whereas logical models do well. WIREs Cogni Sci 2011 2 555-567 DOI:
      10.1002/wcs.134 For further resources related to this article, please visit the
      WIREs website. 

PMID- 26302307
TI  - Pattern classification using functional magnetic resonance imaging.
AB  - Over the past decade, pattern classification methods have become widespread in
      functional magnetic resonance imaging (fMRI). These methods, typically referred
      to as multivoxel pattern analysis (MVPA) or multivariate pattern decoding, are
      now applied to a wide range of neuroscientific questions. There has been
      particular interest in applying these approaches, e.g., in detecting deception or
      for diagnostic purposes. In this review, we will focus on what can be achieved by
      pattern classification analyses of fMRI data; the strengths and weaknesses of
      this approach; and the biological processes giving rise to the signals measured
      by this method. Finally, we will discuss how these multivariate approaches are
      starting to be applied to the analysis of anatomical magnetic resonance imaging
      (MRI) and magnetoencephalographic (MEG) data. WIREs Cogni Sci 2011 2 568-579 DOI:
      10.1002/wcs.141 For further resources related to this article, please visit the
      WIREs website. 

PMID- 26302308
TI  - Predictive coding.
AB  - Predictive coding is a unifying framework for understanding redundancy reduction
      and efficient coding in the nervous system. By transmitting only the unpredicted
      portions of an incoming sensory signal, predictive coding allows the nervous
      system to reduce redundancy and make full use of the limited dynamic range of
      neurons. Starting with the hypothesis of efficient coding as a design principle
      in the sensory system, predictive coding provides a functional explanation for a
      range of neural responses and many aspects of brain organization. The lateral and
      temporal antagonism in receptive fields in the retina and lateral geniculate
      nucleus occur naturally as a consequence of predictive coding of natural images.
      In the higher visual system, predictive coding provides an explanation for
      oriented receptive fields and contextual effects as well as the hierarchical
      reciprocally connected organization of the cortex. Predictive coding has also
      been found to be consistent with a variety of neurophysiological and
      psychophysical data obtained from different areas of the brain. WIREs Cogni Sci
      2011 2 580-593 DOI: 10.1002/wcs.142 For further resources related to this
      article, please visit the WIREs website. 

PMID- 26302309
TI  - Oriented Metallic Nano-Objects on Crystalline Surfaces by Solution Epitaxial
      Growth.
AB  - Chemical methods offer the possibility to synthesize a large panel of
      nanostructures of various materials with promising properties. One of the main
      limitations to a mass market development of nanostructure based devices is the
      integration at a moderate cost of nano-objects into smart architectures. Here we
      develop a general approach by adapting the seed-mediated solution phase synthesis
      of nanocrystals in order to directly grow them on crystalline thin films. Using a
      Co precursor, single-crystalline Co nanowires are directly grown on metallic
      films and present different spatial orientations depending on the crystalline
      symmetry of the film used as a 2D seed for Co nucleation. Using films exposing 6
      fold symmetry surfaces such as Pt(111), Au(111), and Co(0001), the Co
      heterogeneous nucleation and epitaxial growth leads to vertical nanowires self
      organized in dense and large scale arrays. On the other hand, using films
      presenting 4-fold symmetry surfaces such as Pt(001) and Cu(001), the Co growth
      leads to slanted wires in discrete directions. The generality of the concept is
      demonstrated with the use of a Fe precursor which results in Fe nanostructures on
      metallic films with different growth orientations which depend on the 6-fold/4
      fold symmetry of the film. This approach of solution epitaxial growth combines
      the advantages of chemistry in solution in producing shape-controlled and
      monodisperse metallic nanocrystals, and of seeded growth on an ad hoc metallic
      film that efficiently controls orientation through epitaxy. It opens attractive
      opportunities for the integration of nanocrystals in planar devices. 

PMID- 26302310
TI  - Analysis of Phospholipid Bilayers on Gold Nanorods by Plasmon Resonance Sensing
      and Surface-Enhanced Raman Scattering.
AB  - Surface-enhanced Raman scattering (SERS) and localized surface plasmon resonance
      sensing (LSPR) have been applied for a detailed analysis of lipid bilayers at the
      surface of gold nanorods. The spatial dependence of surface enhancement and the
      optical effects of the lipid phase transition confirm the presence of a bilayer
      membrane structure. Deuterated lipids exchanged rapidly between the nanorod
      surface and lipid vesicles in solution, suggesting a loosely bound, natural
      membrane structure. However, at a low solution concentration of lipid vesicles,
      the lipids on the gold nanorod surface convert to a nonbilayer structure, which
      could impact biological applications of these nanomaterials. 

PMID- 26302312
TI  - The Role of a Three Dimensionally Ordered Defect Sublattice on the Acidity of a
      Sulfonated Metal-Organic Framework.
AB  - Understanding the role that crystal imperfections or defects play on the physical
      properties of a solid material is important for any application. In this report,
      the highly unique crystal structure of the metal-organic framework (MOF)
      zirconium 2-sulfoterephthalate is presented. This MOF contains a large number of
      partially occupied ligand and metal cluster sites which directly affect the
      physical properties of the material. The partially occupied ligand positions give
      rise to a continuum of pore sizes within this highly porous MOF, supported by N2
      gas sorption and micropore analysis. Furthermore, this MOF is lined with sulfonic
      acid groups, implying a high proton concentration in the pore, but defective
      zirconium clusters are found to be effective proton trapping sites, which was
      investigated by a combination of AC impedance analysis to measure the proton
      conductivity and DFT calculations to determine the solvation energies of the
      protons in the pore. Based on the calculations, methods to control the pKa of the
      clusters and improve the conductivity by saturating the zirconium clusters with
      strong acids were utilized, and a 5-fold increase in proton conductivity was
      achieved using these methods. High proton conductivity of 5.62 * 10(-3) S cm(-1)
      at 95% relative humidity and 65  degrees C could be achieved, with little change
      down to 40% relative humidity at room temperature. 

PMID- 26302311
TI  - Phenotypic states become increasingly sensitive to perturbations near a
      bifurcation in a synthetic gene network.
AB  - Microorganisms often exhibit a history-dependent phenotypic response after
      exposure to a stimulus which can be imperative for proper function. However,
      cells frequently experience unexpected environmental perturbations that might
      induce phenotypic switching. How cells maintain phenotypic states in the face of
      environmental fluctuations remains an open question. Here, we use environmental
      perturbations to characterize the resilience of phenotypic states in a synthetic
      gene network near a critical transition. We find that far from the critical
      transition an environmental perturbation may induce little to no phenotypic
      switching, whereas close to the critical transition the same perturbation can
      cause many cells to switch phenotypic states. This loss of resilience was
      observed for perturbations that interact directly with the gene circuit as well
      as for a variety of generic perturbations-such as salt, ethanol, or temperature
      shocks-that alter the state of the cell more broadly. We obtain qualitatively
      similar findings in natural gene circuits, such as the yeast GAL network. Our
      findings illustrate how phenotypic memory can become destabilized by
      environmental variability near a critical transition. 

PMID- 26302313
TI  - Surgical and Visual Outcomes of Childhood Glaucoma at a Tertiary Eye Care Center
      in South India.
AB  - PURPOSE: This study aimed to categorize patients with childhood glaucoma into
      groups, study the clinical characteristics of the eyes affected, and determine
      the outcomes after surgery. DESIGN: This was a retrospective, consecutive,
      nonrandomized study. METHODS: Patients with childhood glaucoma who underwent
      planned primary trabeculectomy or combined trabeculotomy-trabeculectomy (CTT)
      between January 2003 and December 2008 were enrolled. Main outcome measures were
      intraocular pressure (IOP), visual acuity, corneal clarity, and any surgical and
      anesthetic complications. RESULTS: One hundred thirty-one eyes of 81 patients
      were included. They were 61.7% male. Mean patient age was 6.1 +/- 4.1 years, and
      the mean age at surgery was 35.8 +/- 40.9 months. Postoperatively, the
      improvement in visual acuity was highly statistically significant at all follow
      ups (P < 0.001). The IOP values showed a significant reduction from 29.2 +/- 9.7
      mm Hg preoperatively to 13.7 +/- 5.3 mm Hg (P < 0.001) at 6-month follow-up and
      12.1 +/- 2.2 mm Hg at last follow-up. Cumulative corneal clarity improved
      significantly postoperatively (P < 0.001). A comparison of trabeculectomy alone
      and CTT showed that both procedures were quite effective. At 1 year, overall
      complete success was seen in 73.3%, qualified success in 16.8%, and failure in
      10.7%. CONCLUSIONS: This study suggests that CTT is safe and effective in both
      primary and secondary childhood glaucomas. Trabeculectomy alone is also highly
      effective in certain cases, and proper case selection is essential to attain
      optimum results. Surgical intervention leads to improvement in vision and corneal
      clarity and also achieves long-term IOP control.

PMID- 26302314
TI  - Modified Approach in Management of Submacular Hemorrhage Secondary to Wet Age
      Related Macular Degeneration.
AB  - PURPOSE: The aim of this study was to evaluate the surgical outcomes of a
      modified approach in the management of thick submacular hemorrhage in patients
      with wet age-related macular degeneration. DESIGN: This was a retrospective
      study. METHODS: A retrospective chart review was performed on 10 eyes of 10
      patients with submacular hemorrhage secondary to wet age-related macular
      degeneration treated with 23-gauge pars plana vitrectomy, followed by submacular
      injection of recombinant tissue plasminogen activator (12.5 MUg/0.1 mL),
      bevacizumab (2.5 mg/0.1 mL), and air (0.3 mL). Gas tamponade was given with 20%
      SF6 and postoperative propped-up positioning. Patients were evaluated for
      displacement of hemorrhage, preoperative and postoperative best-corrected visual
      acuity, occurrence of intraoperative and postoperative complications, and
      recurrence of hemorrhage. All patients were followed up for 6 months. RESULTS:
      Displacement of the submacular bleed was achieved in all cases. Improvement of
      best-corrected visual acuity was seen in 8 of 10 patients. Rebleed was seen in 2
      eyes that were retreated with intravitreal injection of recombinant tissue
      plasminogen activator, bevacizumab, and 20% SF6 gas. CONCLUSIONS: This modified
      technique aids in the effective displacement of thick submacular hemorrhage with
      simultaneous treatment of the underlying choroidal neovascular membrane, which
      halts the disease progression resulting in significant improvement of visual
      acuity.

PMID- 26302315
TI  - Wound Healing Bionanocomposites Based on Castor Oil Polymeric Films Reinforced
      with Chitosan-Modified ZnO Nanoparticles.
AB  - Castor oil (CO), which is a readily available, relatively inexpensive, and
      environmentally benign nonedible oil, has been successfully used as matrix
      material to prepare biocompatible and biodegradable nanocomposite films filled
      with chitosan (CS)-modified ZnO nanoparticles. The biocomposites were synthesized
      via a simple and versatile solution mixing and casting method. The morphology,
      structure, thermal stability, water absorption, biodegradability,
      cytocompatibility, barrier, mechanical, viscoelastic, antibacterial, and wound
      healing properties of the films have been analyzed. FT-IR spectra were used to
      obtain information about the nanoparticle-matrix interactions. The thermal
      stability, hydrophilicity, degree of porosity, water absorption, water vapor
      transmission rate (WVTR), oxygen permeability (Dk), and biodegradability of the
      films increased with the CS-ZnO loading. The WVTR and Dk data obtained are within
      the range of values reported for commercial wound dressings. Tensile tests
      demonstrated that the nanocomposites displayed a good balance between elasticity,
      strength, and flexibility under both dry and simulated body fluid (SBF)
      environments. The flexibility increased in a moist atmosphere due to the
      plasticization effect of absorbed water. The nanocomposites also exhibited
      significantly enhanced dynamic mechanical performance (storage modulus and glass
      transition temperature) than neat CO under different humidity conditions. The
      antibacterial activity of the films against Escherichia coli, Staphylococcus
      aureus, and Micrococcus luteus bacteria was investigated in the presence and the
      absence of UV light. The biocide effect increased progressively with the CS-ZnO
      content and was systematically stronger against Gram-positive cells. Composites
      with nanoparticle loading <=5.0 wt % exhibited very good in vitro
      cytocompatibility and enabled a faster wound healing than neat CO and control
      gauze, hence showing great potential to be applied as antibacterial wound
      dressings. 

PMID- 26302317
TI  - Managing lupus symptoms.

PMID- 26302318
TI  - Recognizing and treating Meckel diverticulum.
AB  - Meckel diverticulum is an uncommon congenital abnormality of the gastrointestinal
      (GI) tract that usually remains asymptomatic throughout a patient's lifetime.
      However, these diverticula can cause complications such as GI bleeding and small
      bowel obstruction; complications occur mostly in children and are rare in adults.
      This article reviews the presentation, complications, and treatment options for
      symptomatic and incidentally found Meckel diverticula. 

PMID- 26302319
TI  - The head and the heart.

PMID- 26302320
TI  - Is combination therapy appropriate for hypothyroidism?
AB  - Levothyroxine is the first-line drug for treating hypothyroidism. This article
      reviews the literature on combination therapy using levothyroxine and
      liothyronine, and found that only one study produced beneficial outcomes; other
      studies reported increased adverse reactions among participants. Levothyroxine
      should remain the drug of choice for hypothyroidism. Adequate trials with
      homogenous populations and large sample sizes are needed to determine whether
      combination therapy can be recommended for patients with hypothyroidism. 

PMID- 26302321
TI  - A painful finger mass in an 8-year-old child.

PMID- 26302322
TI  - Diagnosing and treating severe aplastic anemia.
AB  - Severe aplastic anemia is a disorder of stem cell failure, leading to
      pancytopenia. The condition is characterized by an impairment of the function of
      hematopoietic stem cells. Patients typically have fatigue, infections, and
      increased or unusual bleeding. A bone marrow biopsy establishes the diagnosis.
      Treatment includes hematopoietic stem cell transplant or immunosuppressive
      therapy.

PMID- 26302323
TI  - Hip pain in young adults: diagnosing femoroacetabular impingement.
AB  - Symptomatic femoroacetabular impingement (FAI) predisposes patients to developing
      early osteoarthritis. This article reviews the criteria for diagnosing FAI,
      management strategies, and when to refer patients to an orthopedic provider for
      further evaluation and possible surgical intervention.

PMID- 26302324
TI  - In which states are physician assistants or nurse practitioners more likely to
      work in primary care?
AB  - OBJECTIVE: Examine availability of physician assistants (PAs) or nurse
      practitioners (NPs) in primary care physician practices by state and by state PA
      and NP scope-of-practice laws. METHODS: Availability of PAs and NPs in primary
      care practices was examined in multivariate analysis using a 2012 state-based,
      nationally representative survey of office-based physicians. Covariates included
      practice characteristics, state, and in a separate model, PA and NP scope-of
      practice variables. RESULTS: After controlling for practice characteristics,
      higher use of PAs and NPs was found in three states (Minnesota, Montana, and
      South Dakota). In a separate model, higher use of PAs or NPs was associated with
      favorable PA scope-of-practice laws, but not with NP scope-of-practice laws.
      CONCLUSIONS: Higher availability of PAs or NPs was associated with favorable PA
      scope-of-practice laws. Lack of association between PA or NP availability and NP
      scope-of-practice laws requires further investigation.

PMID- 26302325
TI  - Irritable bowel syndrome.

PMID- 26302327
TI  - A lesion near the eye.

PMID- 26302330
TI  - Thermal and transport properties of U2Pt(x)Ir(1-x)C2.
AB  - We report thermal and transport properties of U2Pt x Ir1-x C2 from which a
      magnetic phase diagram is obtained. Pure U2IrC2 is an antiferromagnet at 6.5 K,
      whose Neel temperature initially rises to 13.2 K at x = 0.2 and subsequently is
      suppressed to zero temperature with increasing Pt content near x = 0.6. Heat
      capacity divided by temperature at x = 0.6 shows an upturn at low temperature,
      consistent with the expectations of enhanced quantum fluctuations in the presence
      of an underlying quantum critical point. The entropy after the phonon
      contribution has been subtracted has a value of 0.24 Rln2 at the Neel temperature
      of U2IrC2, revealing an itinerant nature of the 5 f electrons in this compound.
      On the Pt rich side of the phase diagram, superconductivity is suppressed by x =
      0.85. The residual resistivity increases by a factor of 10 from pure Pt (x = 1)
      to x = 0.85 where superconductivity is suppressed to zero. By comparing the phase
      diagram of Ir doped U2PtC2 with the phase diagram of pressure tuned and Rh doped
      U2PtC2 we demonstrate the role of electronic tuning in this system. 

PMID- 26302329
TI  - Tumor Suppressor WWOX Contributes to the Elimination of Tumorigenic Cells in
      Drosophila melanogaster.
AB  - WWOX is a >1 Mb gene spanning FRA16D Common Chromosomal Fragile Site, a region of
      DNA instability in cancer. Consequently, altered WWOX levels have been observed
      in a wide variety of cancers. In vitro studies have identified a large number and
      variety of potential roles for WWOX. Although its normal role in vivo and
      functional contribution to cancer have not been fully defined, WWOX does have an
      integral role in metabolism and can suppress tumor growth. Using Drosophila
      melanogaster as an in vivo model system, we find that WWOX is a modulator of
      TNFalpha/Egr-mediated cell death. We found that altered levels of WWOX can modify
      phenotypes generated by low level ectopic expression of TNFalpha/Egr and this
      corresponds to altered levels of Caspase 3 activity. These results demonstrate an
      in vivo role for WWOX in promoting cell death. This form of cell death is
      accompanied by an increase in levels of reactive oxygen species, the regulation
      of which we have previously shown can also be modified by altered WWOX activity.
      We now hypothesise that, through regulation of reactive oxygen species, WWOX
      constitutes a link between alterations in cellular metabolism observed in cancer
      cells and their ability to evade normal cell death pathways. We have further
      shown that WWOX activity is required for the efficient removal of tumorigenic
      cells from a developing epithelial tissue. Together these results provide a
      molecular basis for the tumor suppressor functions of WWOX and the better
      prognosis observed in cancer patients with higher levels of WWOX activity.
      Understanding the conserved cellular pathways to which WWOX contributes provides
      novel possibilities for the development of therapeutic approaches to restore WWOX
      function in cancer.

PMID- 26302331
TI  - Gold nanoparticle-siRNA mediated oncogene knockdown at RNA and protein level,
      with associated gene effects.
AB  - AIMS: RNAi is a powerful tool for gene silencing that can be used to reduce
      undesirable overexpression of oncogenes as a novel form of cancer treatment.
      However, when using RNAi as a therapeutic tool there is potential for associated
      gene effects. This study aimed to utilize gold nanoparticles to deliver siRNA
      into HeLa cells. RESULTS: Knockdown of the c-myc oncogene by RNAi, at the RNA,
      protein and cell proliferation level was achieved, while also identifying
      associated gene responses. DISCUSSION: The gold nanoparticles used in this study
      present an excellent delivery platform for siRNA, but do note associated gene
      changes. CONCLUSION: The study highlights the need to more widely assess the cell
      physiological response to RNAi treatment, rather than focus on the immediate RNA
      levels.

PMID- 26302332
TI  - Temporal Stability of Genetic Structure in a Mesopelagic Copepod.
AB  - Although stochasticity in oceanographic conditions is known to be an important
      driver of temporal genetic change in many marine species, little is known about
      whether genetically distinct plankton populations can persist in open ocean
      habitats. A prior study demonstrated significant population genetic structure
      among oceanic gyres in the mesopelagic copepod Haloptilus longicornis in both the
      Atlantic and Pacific Oceans, and we hypothesized that populations within each
      gyre represent distinct gene pools that persist over time. We tested this
      expectation through basin-scale sampling across the Atlantic Ocean in 2010 and
      2012. Using both mitochondrial (mtCOII) and microsatellite markers (7 loci), we
      show that the genetic composition of populations was stable across two years in
      both the northern and southern subtropical gyres. Genetic variation in this
      species was partitioned among ocean gyres (FCT = 0.285, P < 0.0001 for mtCOII,
      FCT = 0.013, P < 0.0001 for microsatellites), suggesting strong spatial
      population structure, but no significant partitioning was found among sampling
      years. This temporal persistence of population structure across a large
      geographic scale was coupled with chaotic genetic patchiness at smaller spatial
      scales, but the magnitude of genetic differentiation was an order of magnitude
      lower at these smaller scales. Our results demonstrate that genetically distinct
      plankton populations persist over time in highly-dispersive open ocean habitats,
      and this is the first study to rigorously test for temporal stability of large
      scale population structure in the plankton. 

PMID- 26302333
TI  - Personally important posttraumatic growth in adolescents: The effect on self
      esteem beyond commonly defined posttraumatic growth.
AB  - Research on posttraumatic growth (PTG), positive psychological changes that may
      occur as a result of highly stressful life events, reveals adolescents are able
      to experience PTG. The current study tests individual differences among
      adolescents in relative importance of PTG and examines the relationships among
      personally important PTG, commonly defined PTG, and self-esteem. Adolescents (N =
      145) with the mean age of 15.75 (SD = 1.13) completed the Rosenberg Self-Esteem
      Scale and PTG Inventory, and then reported which items on the PTG Inventory were
      personally important to them. Results indicated within-scale differences in item
      importance on the PTG Inventory. Personally important PTG was a better predictor
      of adolescent self-esteem than commonly defined PTG, measured as total PTGI score
      or each of the five factors. These findings suggest future research should look
      at both short-term and long-term effects of personally important PTG as well as
      commonly defined PTG. 

PMID- 26302334
TI  - The impact of Sleep Time-Related Information and Communication Technology
      (STRICT) on sleep patterns and daytime functioning in American adolescents.
AB  - This cross-sectional study explored the extent and impact of mobile device-based
      Sleep Time-Related Information and Communication Technology (STRICT) use among
      American adolescents (N = 3139, 49.3% female, mean age = 13.3 years). Nearly 62%
      used STRICT after bedtime, 56.7% texted/tweeted/messaged in bed, and 20.8% awoke
      to texts. STRICT use was associated with insomnia, daytime sleepiness,
      eveningness, academic underperformance, later bedtimes and shorter sleep
      duration. Moderation analysis demonstrated that the association between STRICT
      use and insomnia increased with age, the association between STRICT use and
      daytime sleepiness decreased with age, and the association between STRICT use and
      shorter sleep duration decreased with age and was stronger in girls. Insomnia and
      daytime sleepiness partially mediated the relationship between STRICT use and
      academic underperformance. Our results illustrate the adverse interactions
      between adolescent STRICT use and sleep, with deleterious effects on daytime
      functioning. These worrisome findings suggest that placing reasonable limitations
      on adolescent STRICT use may be appropriate. 

PMID- 26302335
TI  - Role of GRP78 in promoting therapeutic-resistant breast cancer.
AB  - Over 230,000 new cases of invasive breast cancer are diagnosed annually within
      the USA. Recurrent breast cancer remains a mostly incurable disease with drug
      resistance, tumor latency and distant metastases driving breast tumor recurrence
      and morbidity. Understanding drug resistance is a critical component of combating
      breast cancer. Recently, the protein chaperone GRP78 and the unfolded protein
      response were implicated as drivers of drug resistance. Preclinical studies show
      inhibiting GRP78 can reverse drug resistance. Furthermore, drugs developed to
      target GRP78 show clinical promise in several ongoing clinical trials. 

PMID- 26302336
TI  - Exposure Estimation and Interpretation of Occupational Risk: Enhanced Information
      for the Occupational Risk Manager.
AB  - The fundamental goal of this article is to describe, define, and analyze the
      components of the risk characterization process for occupational exposures.
      Current methods are described for the probabilistic characterization of exposure,
      including newer techniques that have increasing applications for assessing data
      from occupational exposure scenarios. In addition, since the probability of
      health effects reflects variability in the exposure estimate as well as the dose
      response curve-the integrated considerations of variability surrounding both
      components of the risk characterization provide greater information to the
      occupational hygienist. Probabilistic tools provide a more informed view of
      exposure as compared to use of discrete point estimates for these inputs to the
      risk characterization process. Active use of such tools for exposure and risk
      assessment will lead to a scientifically supported worker health protection
      program. Understanding the bases for an occupational risk assessment, focusing on
      important sources of variability and uncertainty enables characterizing
      occupational risk in terms of a probability, rather than a binary decision of
      acceptable risk or unacceptable risk. A critical review of existing methods
      highlights several conclusions: (1) exposure estimates and the dose-response are
      impacted by both variability and uncertainty and a well-developed risk
      characterization reflects and communicates this consideration; (2) occupational
      risk is probabilistic in nature and most accurately considered as a distribution,
      not a point estimate; and (3) occupational hygienists have a variety of tools
      available to incorporate concepts of risk characterization into occupational
      health and practice. 

PMID- 26302337
TI  - Pain volatility and prescription opioid addiction treatment outcomes in patients
      with chronic pain.
AB  - The combination of prescription opioid dependence and chronic pain is
      increasingly prevalent and hazardous to public health. Variability in pain may
      explain poor prescription opioid addiction treatment outcomes in persons with
      chronic pain. This study examined pain trajectories and pain volatility in
      patients with chronic pain receiving treatment for prescription opioid addiction.
      We conducted secondary analyses of adults with chronic pain (n = 149) who
      received buprenorphine/naloxone (BUP/NLX) and counseling for 12 weeks in an
      outpatient, multisite clinical trial. Good treatment outcome was defined as urine
      verified abstinence from opioids at treatment endpoint (Week 12) and during at
      least 2 of the previous 3 weeks. Pain severity significantly declined over time
      during treatment (b = -0.36, p < .001). Patients with greater pain volatility
      were less likely to have a good treatment outcome (odds ratio = 0.55, p < .05),
      controlling for baseline pain severity and rate of change in pain over time. A 1
      standard deviation increase in pain volatility was associated with a 44%
      reduction in the probability of endpoint abstinence. The significant reduction in
      subjective pain during treatment provides observational support for the analgesic
      effects of BUP/NLX in patients with chronic pain and opioid dependence. Patients
      with greater volatility in subjective pain during treatment have increased risk
      of returning to opioid use by the conclusion of an intensive treatment with
      BUP/NLX and counseling. Future research should examine underlying mechanisms of
      pain volatility and identify related therapeutic targets to optimize
      interventions for prescription opioid addiction and co-occurring chronic pain.

PMID- 26302338
TI  - Boundary conditions of methamphetamine craving.
AB  - Methamphetamine use has increased significantly and become a global health
      concern. Craving is known to predict methamphetamine use and relapse following
      abstinence. Some have suggested that cravings are automatic, generalized, and
      uncontrollable, but experimental work addressing these claims is lacking. In 2
      exploratory studies, we tested the boundary conditions of methamphetamine craving
      by asking: (a) is craving specific to users' preferred route of administration?,
      and (b) can craving be regulated by cognitive strategies? Two groups of
      methamphetamine users were recruited. In Study 1, participants were grouped by
      their preferred route of administration (intranasal vs. smoking), and rated their
      craving in response to photographs and movies depicting methamphetamine use (via
      the intranasal vs. smoking route). In Study 2, methamphetamine smokers
      implemented cognitive regulation strategies while viewing photographs depicting
      methamphetamine smoking. Strategies involved either focusing on the positive
      aspects of smoking methamphetamine or the negative consequences of doing so-the
      latter strategy based on treatment protocols for addiction. In Study 1, we found
      a significant interaction between group and route of administration, such that
      participants who preferred to smoke methamphetamine reported significantly
      stronger craving for smoking stimuli, whereas those who preferred the intranasal
      route reported stronger craving for intranasal stimuli. In Study 2, participants
      reported significantly lower craving when focusing on the negative consequences
      associated with methamphetamine use. Taken together, these findings suggest that
      strength of craving for methamphetamine is moderated by users' route of
      administration and can be reduced by cognitive strategies. This has important
      theoretical, methodological, and clinical implications.

PMID- 26302339
TI  - The Flavone Luteolin Suppresses SREBP-2 Expression and Post-Translational
      Activation in Hepatic Cells.
AB  - High blood cholesterol has been associated with cardiovascular diseases. The
      enzyme HMG CoA reductase (HMGCR) is responsible for cholesterol synthesis, and
      inhibitors of this enzyme (statins) have been used clinically to control blood
      cholesterol. Sterol regulatory element binding protein (SREBP) -2 is a key
      transcription factor in cholesterol metabolism, and HMGCR is a target gene of
      SREBP-2. Attenuating SREBP-2 activity could potentially minimize the expression
      of HMGCR. Luteolin is a flavone that is commonly detected in plant foods. In the
      present study, Luteolin suppressed the expression of SREBP-2 at concentrations as
      low as 1 MUM in the hepatic cell lines WRL and HepG2. This flavone also prevented
      the nuclear translocation of SREBP-2. Post-translational processing of SREBP-2
      protein was required for nuclear translocation. Luteolin partially blocked this
      activation route through increased AMP kinase (AMPK) activation. At the
      transcriptional level, the mRNA and protein expression of SREBP-2 were reduced
      through luteolin. A reporter gene assay also verified that the transcription of
      SREBF2 was weakened in response to this flavone. The reduced expression and
      protein processing of SREBP-2 resulted in decreased nuclear translocation. Thus,
      the transcription of HMGCR was also decreased after luteolin treatment. In
      summary, the results of the present study showed that luteolin modulates HMGCR
      transcription by decreasing the expression and nuclear translocation of SREBP-2. 

PMID- 26302340
TI  - Using Sodium Oxybate (Gamma Hydroxybutyric Acid) for Deep Sedation at the End of
      Life.

PMID- 26302341
TI  - A Biomimetic Mechanism for the Copper-Catalyzed Aerobic Oxygenation of 4-tert
      Butylphenol.
AB  - Controlling product selectivity during the catalytic aerobic oxidation of phenols
      remains a significant challenge that hinders reaction development. This work
      provides a mechanistic picture of a Cu-catalyzed, aerobic functionalization of
      phenols that is selective for phenoxy-coupled ortho-quinones. We show that the
      immediate product of the reaction is a Cu(II)-semiquinone radical complex and
      reveal that ortho-oxygenation precedes oxidative coupling. This complex is the
      resting state of the Cu catalyst during turnover at room temperature. A
      mechanistic study of the formation of this complex at low temperatures
      demonstrates that the oxygenation pathway mimics the dinuclear Cu enzyme
      tyrosinase by involving a dinuclear side-on peroxodicopper(II) oxidant. Unlike
      the enzyme, however, the rate-limiting step of the ortho-oxygenation reaction is
      the self-assembly of the oxidant from Cu(I) and O2. We provide details for all
      steps in the cycle and demonstrate that turnover is contingent upon proton
      transfer events that are mediated by a slight excess of ligand. Finally, our
      knowledge of the reaction mechanism can be leveraged to diversify the reaction
      outcome. Thus, uncoupled ortho-quinones are favored in polar, coordinating media,
      highlighting unusually high levels of chemoselectivity for a catalytic aerobic
      oxidation of a phenol. 

PMID- 26302342
TI  - [Study of the Changes on Tree Shrew Bronchial Epithelium ?Induced by Xuanwei
      Bituminous Coal Dust].
AB  - BACKGROUND AND OBJECTIVE: Lung cancer is the type of cancer with the highest
      incidence and mortality in numerous countries and regions. Establishing an
      appropriate animal model that can be used to simulate lung cancer etiology,
      pathogenesis, and similar processes, is urgent. We explore the feasibility of
      establishing a lung cancer model induced by Xuanwei bituminous coal dust PM10
      (particulate matter with diameters of 10 MUm or less), which affects bronchial
      epithelium of tree shrews. METHODS: The neck skin of adult tree shrews is
      dissected, and the thyroid cartilage is fully exposed. Subsequently, the weak
      part at the top of the thyroid cartilage is treated with intratracheal agents by
      perfusion via a special infusion needle puncture method. Regular X-ray
      examination and lung tissue biopsy were performed on the sacrificed animals to
      observe changes in pulmonary imaging and bronchial epithelial cells after
      perfusion of Xuanwei bituminous coal dust PM 10. RESULTS: The tree shrews of the
      experimental group (exposed to bituminous coal dust) died in a week after
      perfusion with PM10, whereas no animal died until the end of the experiment in
      the blank control and the solvent control groups. Sections of lung tissue biopsy
      of the regularly killed tree shrews were stained with hematoxylin and eosin. The
      lung tissues of tree shrews in the experimental group showed a serial changes
      caused by bronchial epithelial hyperplasia, such as squamous metaplasia,
      dysplasia, and early invasive carcinoma, whereas no significant pathological
      changes were observed in the blank control and solvent control groups.
      CONCLUSIONS: Endotracheal infusion of Xuanwei bituminous coal dust PM10 induces
      lung cancer in tree shrews. Thus, the lung cancer model was established.?.

PMID- 26302343
TI  - [Ionizing Radiation Reduces TKI Resistance Caused by T790M Mutation in NSCLC Cell
      Lines].
AB  - BACKGROUND AND OBJECTIVE: Epidermal growth factor receptor-tyrosine kinase
      inhibitor (EGFR-TKI), which targets EGFR, plays an important role in non-small
      cell lung cancer (NSCLC) treatment. Patients with somatic activating mutations in
      the EGFR gene exhibit significant initial response but eventually develop
      resistance to TKI. The second mutation (T790M) of the EGFR gene is the possible
      main cause of drug resistance. The aim of this study is to investigate the effect
      of ionizing radiation on EGFR-TKI resistance caused by T790M mutation in NSCLC
      cell lines. METHODS: We selected H1975 and H3255 as research subjects and tested
      the mutation states by real-time PCR analysis. Radiosensitivity was determined by
      clone-forming test, and drug resistance was detected in different groups by MTT
      assay. RESULTS: H1975 is an EGFR double mutant (L858R plus T790M), whereas H3255
      is an EGFR single mutant (L858R). The cell survival fractions of H1975 and H3255
      did not vary in different treatment groups (P=0.952). Thus, T790M mutation did
      not affect the radiosensitivity of NSCLC cell lines. The IC50 of H1975 in the 2.5
      Gy group [(0.678; 2+/-0.373) MUmol/L] was statistically significant compared with
      that in the 0 Gy normal control group [(3.520+/-0.821) MUmol/L] (P=0.008). The
      drug tolerance of the H1975 cell line by 89.5 dropped to 39.2 times. CONCLUSIONS:
      Ionizing radiation can reduce TKI resistance caused by T790M mutation in NSCLC
      cell lines. Our results provide a research basis for future in vivo and clinical
      studies. Radiotherapy combined with EGFR-TKI treatment can be a promising
      strategy to overcome T790M-mediated drug resistance.?.

PMID- 26302344
TI  - [Influence of Berberine on Cisplatin Antineoplastic Effect in A549 Cells].
AB  - BACKGROUND AND OBJECTIVE: Cisplatin is a standard first-line chemotherapeutic
      agents for treating advanced non-small cell lung cancer. Unfortunately, the
      clinical application cisplatin is restricted because it induces serious adverse
      reaction. The aim of this study is to investigate the influence and probable
      mechanism of berberine on cisplatin antineoplastic effect on lung cancer A549
      cells. METHODS: The total Cx43 protein amount, localization of Cx43 on cell
      membrane, and gap junction function were observed after the A549 cells were
      treated with berberine. The influence of berberine on the antitumor action of
      cisplatin was detected by standard colony-forming assay. Protein kinase C (PKC)
      protein, which regulates the gap junction, was subsequently determined. RESULTS:
      Berberine did not affect cell survival at concentrations of 0 MUM to 10 MUM in
      the A549 cells. The gap junction function between the cells was enhanced through
      increased Cx43 protein expression and localization of Cx43 on the membrane after
      berberine treatment. The intercellular dye coupling through gap junction
      increased when the cells exposed to 0.1 MUM, 1 MUM, 10 MUM berberine [33.3%
      (P=0.002,3), 67.0% (P<0.001), 160.0% (P<0.001)] compared withcontrols. This
      effect was associated with the PKC activity. The cisplatin-induced inhibition of
      colony growth was enhanced when berberine was combined with cisplatin.
      CONCLUSIONS: Berberine can obviously increase the antitumor effect of cisplatin
      by enhancing the function of the gap junction possibly in A549 cells.?.

PMID- 26302345
TI  - [Effect of Long Non-coding RNA SPRY4-IT1 on Invasion and Migration of A549
      Cells].
AB  - BACKGROUND AND OBJECTIVE: The abnormal expression of human long chain non
      encoding RNA gene is related to many kinds of tumors. The aim of this study is to
      investigate the expression of long non-coding RNA maternally expressed gene 3
      (SPRY4-IT1) in lung cancer (A549) cells, and to observe the effect of SPRY4-IT1
      on the invasion and migration of A549 cells. METHODS: The levels of SPRY4-IT1 in
      A549 was detected by Real-time PCR. The effects of SPRY4-IT1 on the invasion and
      migration of A549 cell were analyzed by MTT and Transwell assay. The expression
      of matrix metalloproteinase (MMP) family proteins was determined by Western blot.
      RESULTS: The invasion and migration of A549 cells were increased after SPRY4-IT1
      over-expression. The cell spaces were narrower after SPRY4-IT1 over expression in
      the wound healing assay. Transwell assays showed that the numbers of
      transmembrane A549 cells were significantly higher in SPRY4-IT1 over expression
      group than that in control group (P<0.05). Meanwhile, over expression of SPRY4
      IT1 reduced the expression of MMP-2 and MMP-9. CONCLUSIONS: Over expression of
      SPRY4-IT1 enhanced the invasion and migration of A549 cells. MMP-2 and MMP-9
      might play an important role in this regulation.?.

PMID- 26302346
TI  - [Effectiveness of Tyrosine Kinase Inhibitors on Uncommon Epidermal Growth Factor
      ?Receptor Mutations in Non-small Cell Lung Cancer].
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) mutations occur more
      frequently in non-small cell lung cancer (NSCLC) of women, never smokers, Asian
      population and those with adenocarcinoma. Short in-frame deletion in exon 19 and
      L858R substitution are the most common mutations, which are closely associated
      with EGFR tyrosine kinase inhibitors (TKIs) treatment response. However, the
      therapeutic effects of EGFR-TKIs on NSCLC with uncommon EGFR mutation subtypes
      remain unclear. The aim of this study is to investigate the clinicopathologic
      feature of uncommon EGFR mutations and the outcomes of these patients. METHODS:
      Twenty-four patients that harbored uncommon EGFR mutations were included in this
      study. Clinicopathologic features of uncommon EGFR mutations and the outcomes of
      these patients were analyzed. RESULTS: Of the 24 patients, 13 received EGFR-TKIs
      treatment. The response rate of EGFR-TKIs treatment was 46.1%, and the median
      progression-free survival (PFS) was 7.4 months. Mutations on S768I and L861Q
      composed a major part (8 of 24) of uncommon mutations. CONCLUSIONS: Uncommon EGFR
      mutations constituted a unique part of the whole group of EGFR mutations. Their
      composition and sensitivity to EGFR-TKIs were heterogeneous, which requires
      further assessment in a prospective study.

PMID- 26302347
TI  - [Clinical Observation of Recombinant Human Vascular Endostatin Durative
      Transfusion Combined with Window Period Arterial Infusion Chemotherapy in the
      Treatment of ?Advanced Lung Squamous Carcinoma].
AB  - BACKGROUND AND OBJECTIVE: Lung cancer is one of the most common malignant tumors
      in China. The aim of this study is to observe the efficacy and safety of
      recombinant human vascular endostatin (endostar) durative transfusion combined
      with window period arterial infusion chemotherapy in the treatment of advanced
      lung squamous carcinoma. METHODS: From February 2014 to January 2015, 10 cases of
      the cytological or histological pathology diagnosed stage IIIb - stage IV lung
      squamous carcinoma were treated with recombinant human vascular endostatin (30
      mg/d) durative transfusion combined with window period arterial infusion
      chemotherapy. Over the same period of 10 cases stage IIIb - stage IV lung
      squamous carcinoma patients for pure arterial perfusion chemotherapy were
      compared. Recombinant human vascular endostatin was durative transfused every 24
      hours for 7 days in combination group, and in the 4th day of window period, the
      10 patients were received artery infusion chemotherapy, using docetaxel combined
      with cisplatin. Pure treatment group received the same arterial perfusion
      chemotherapy regimen. 4 weeks was a cycle. 4 weeks after 2 cycles, to evaluate
      the short-term effects and the adverse drug reactions. RESULTS: 2 groups of
      patients were received 2 cycles treatments. The response rate (RR) was 70.0%, and
      the disease control rate (DCR) was 90.0% in the combination group; In the pure
      treatment group were 50.0%, 70.0% respectively, there were no statistically
      significant difference (P=0.650, 0.582). The adverse reactions of the treatment
      were mild, including level 1-2 of gastrointestinal reaction and blood toxicity,
      there were no statistically significant difference (P=0.999, P=0.628). In the
      combination group, 1 patient occurred level 1 of cardiac toxicity. CONCLUSIONS:
      Recombinant human vascular endostatin durative transfusion combined with window
      period arterial infusion chemotherapy in the treatment of advanced lung squamous
      carcinoma could take a significant curative effect, and the patients were well
      tolerated by the mild adverse reactions.

PMID- 26302348
TI  - [Survival Analysis of 121 Stage N2-IIIa Non-small Cell Lung Cancer Patients
      ?Treated with Surgery].
AB  - BACKGROUND AND OBJECTIVE: It has still been controversial to treat N2-IIIa non
      small cell lung cancer (NSCLC) patients by surgery or non-surgery. We
      retrospectively analysed the survival of 121 stage N2-IIIa NSCLC patients treated
      with surgery and explored their postoperatively long-term prognostic factors.
      METHODS: All of 1,290 patients in Beijing Cancer Hospital underwent resection by
      single-surgeon-team, among which 121 cases with stage N2-IIIa were enrolled in
      the study. We retrospectively analysed the impact of gender, age, smoking,
      perioperative chemotherapy, incision, histological type, vascular tumor emboli,
      pTstage and tumor size on survival of stage N2-IIIa patients, and compared the
      survival between patients with single-and multi-station N2 metastasis, and
      between intraoperatively or postoperatively pathological N2 (IIIa1/a2) and
      preoperative N2 (IIIa3/a4). Univariate analysis was conducted by Kaplan-Meier
      curve, and significance test was performed by Log-rank test and Cox regression
      factor analysis was applicated for multivariate analysis. RESULTS: The 5-yr of
      all the 121 cases was 43.6%, with a median survival time being 50.3 mo.
      Univariate analysis showed the 5-year survival rate in patients with single- and
      multi- station N2 metastasis were 58.3% and 25.5%, respectively (P=0.001), 5-year
      survival rate in patients with stage IIIa1/a2 and stag IIIa3/a4 were 52.7% and
      38.4%, respectively (P=0.020). Multivariate analysis demonstrated that only
      single station N2 (HR=0.326, 95%CI: 0.186-0.572, P<0.001) and IIIa1/a2 (HR=0.494,
      95%CI: 0.259-0.941, P=0.032) were independent prognostic factors for stage N2
      IIIa lung cancer patients. CONCLUSIONS: The prognosis of stage N2-IIIa NSCLC
      patients with single-station N2 metastasis were better than those with multi
      station N2 metastasis. Besides, IIIa1/a2 patients had a better survival compared
      with stage IIIa3/a4 patients. A multi-disciplinary comprehensive treatment based
      on surgery may allow patients with high selective stage N2-IIIa NSCLC to obtain a
      comparatively satisfying long-term survival.?.

PMID- 26302349
TI  - [What are the Advantages? A Prospective Analysis of 16 versus 28 French Chest
      Tube Sizes in Video-assisted Thoracoscopic Surgery Lobectomy of Lung Cancer].
AB  - BACKGROUND AND OBJECTIVE: Post-operation management of minimally invasive
      thoracic surgery is similar to that of open surgery, especially on the drainage
      tube of the chest. The aim of this study is to compare the advantages of using 16
      F versus 28 F chest tubes in video-assisted thoracoscopic surgery (VATS)
      lobectomy of lung cancer. METHODS: Data from 163 patients (February-May 2014) who
      underwent VATS lobectomy of lung cancer with insertion of one chest drain (16 F
      or 28 F) were analyzed. The following post-operative data were evaluated: primary
      healing of tube incision, CXR abnormalities (pneumothorax, fluid, atelectasis,
      subcutaneous emphysema, and hematoma), drainage time, new drain insertion, and
      wound healing at the site of insertion. RESULTS: A total of 75 patients received
      28 F chest tubes, and 88 patients received 16 F chest tubes. Both groups were
      similar in age, gender, comorbidities, and pathological evaluation of resection
      specimens. After adjustment, no statistically significant difference was found
      between the two groups in relation to tube-related complications including
      residual pneumothoraces (4.00% vs 4.44%; P=0.999), subcutaneous emphysema (8.00%
      vs 6.67%; P=0.789), retained hemothorax (0 vs 41%, P=0.253), and drainage time
      [(28.4+/-16.12) h vs (22.1+/-11.8) h; P=0.120)] The average total drainage volume
      and rrhythmia rates of the 16 F group [(365+/-106) mL, 14.67%)] was less than
      that of the 28 F group [(665+/-217) mL, 4.5%; P=0.030, P=0.047]. The rates of
      primary healing at the site of insertion in the 16 F group (95.45%) was higher
      than that in the 28 F group (77.73%, P=0.039). A significant difference was found
      on the post-operative length of stay of the two groups [(4.23+/-0.05) d vs
      (4.57+/-0.16) d, P=0.078]. CONCLUSIONS: The use of 16 F chest tube for VATS
      lobectomy of patients with lung cancer did not affect the clinically relevant
      outcomes tested. However, 16 F chest tube facilitated faster wound healing at the
      site of insertion.?.

PMID- 26302350
TI  - [Research Progress of Mechanisms on Intracranial Metastasis of Non-small Cell
      Lung Cancer after Clinical Benefit from EGFR-TKI].
AB  - Currently epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)
      is widely used for treatment of non-small cell lung cancer (NSCLC) patients with
      EGFR mutation. However, intracranial metastasis and progression could happen to
      some patients while their primary tumors in lung stabilize or even shrink after
      EGFR-TKI treatment. And mechanisms on this phenomenon remain unclear. Recently,
      increasing studies have demonstrated that it is associated with the
      pharmacokinetics of EGFR-TKI, heterogeneity between primary tumors and
      metastases, EGFR mutation status and prolonged survival. Therefore, we write this
      review to discuss the mechanisms on intracranial metastasis of NSCLC after
      clinical benefit from EGFR-TKI. 

PMID- 26302351
TI  - [Huge Solitary Fibrous Tumor of Pleura Combined with Peripheral Pulmonary Artery
      Aneurysm: A Case Resport].
AB  - Solitary fibrous tumor of pleura (SFTP) is uncommon, accounts for less than 5% of
      all pleural tumors. Pulmonary artery aneurysm (PAA) is also not common, 80% of
      which often occurs in the main pulmonary trunk and peripheral PAA is rare. SFTP
      combined with PAA in one patient has not been reported. This paper reports a case
      of SFTP combined with peripheral PAA, and SFTP maybe accelerate PAA formation. 

PMID- 26302352
TI  - [A Case of Death Secondary to Phrenic Nerve Palsy after Huge Mediastinal Teratoma
      ?Resection in Newborn].
AB  - Neonatal teratomas, not common in clinical, are often some case reports, female
      more than male, most are benign. It can occur anywhere of body midline;
      sacrococcygeal teratoma is the most common and the second most frequent site of
      extragonadal teratomas is mediastinum. Benign is more commom and malignant is
      very rarely seen. Completely surgical resection is the main and effective
      treatment. This review reports a case of neonatal teratoma, which is complicated
      with a fatal phrenic nerve palsy after surgery. 

PMID- 26302353
TI  - Characterizing Apolipoprotein E epsilon4 Carriers and Noncarriers With the
      Clinical Diagnosis of Mild to Moderate Alzheimer Dementia and Minimal beta
      Amyloid Peptide Plaques.
AB  - IMPORTANCE: beta-Amyloid peptide (Abeta) plaques are a cardinal neuropathologic
      feature of Alzheimer disease (AD), yet more than one-third of apolipoprotein E
      epsilon4 (APOE4) noncarriers with the clinical diagnosis of mild to moderate
      Alzheimer dementia may not meet positron emission tomographic criteria for
      significant cerebral amyloidosis. OBJECTIVES: To clarify the percentage of APOE4
      carriers and noncarriers with the primary clinical diagnosis of mild to moderate
      Alzheimer dementia near the end of life and minimal Abeta plaques noted at
      autopsy and the extent to which these cases are associated with appreciable
      neurofibrillary degeneration or a primary neuropathologic diagnosis other than
      AD. DESIGN, SETTING, AND PARTICIPANTS: Data on participants included in this
      study were obtained from the National Alzheimer Coordinating Center's Uniform
      Data Set, which comprises longitudinal clinical assessments performed at the AD
      centers funded by the National Institute on Aging. Neuropathology data are
      available for the subset of participants who died. A total of 100 APOE4
      noncarriers and 100 APOE4 carriers had the primary clinical diagnosis of mild to
      moderate Alzheimer dementia at their last visit, known APOE4 genotype, died
      within the ensuing 24 months, and underwent neuropathologic evaluation on
      autopsy. The study was conducted from September 1, 2005, to September 1, 2012;
      analysis was performed from October 9, 2012, to March 20, 2015. MAIN OUTCOMES AND
      MEASURES: Standardized histopathologic assessments of AD neuropathologic changes
      were the primary measures of interest in this study, specifically Consortium to
      Establish a Registry for Alzheimer's Disease neuritic plaque density score,
      diffuse plaque density score, and Braak stage for neurofibrillary degeneration.
      The distributions of scores for these measures were the primary outcomes.
      RESULTS: Of the 37 APOE4 noncarriers with minimal neuritic plaques, 16
      individuals (43.2%) had Braak stages III to VI ratings, and 15 of the others
      (75.0%) met neuropathologic criteria for other dementia-related diseases. Of the
      13 APOE4 carriers with minimal neuritic plaques, 6 individuals (46.2%) had Braak
      stages III to VI ratings and met neuropathologic criteria for other dementia
      related diseases. Similarly, of the 7 APOE4 carriers with minimal neuritic
      plaques and Braak stages 0 to II, 4 participants (57.1%) were thought to have
      pathologic changes and alterations resulting from non-AD neuropathologic
      features. CONCLUSIONS AND RELEVANCE: In this study, more than one-third of APOE4
      noncarriers with the primary clinical diagnosis of mild to moderate Alzheimer
      dementia had minimal Abeta plaque accumulation in the cerebral cortex and, thus,
      may show limited or no benefit from otherwise effective anti-Abeta treatment.
      Almost half of the participants with a primary clinical diagnosis of mild to
      moderate Alzheimer dementia and minimal Abeta plaque accumulation had an
      extensive topographic distribution of neurofibrillary degeneration. Additional
      studies are needed to better understand and provide treatment for patients with
      this unexpectedly common cliniconeuropathologic condition.

PMID- 26302355
TI  - Transcriptomics of colour patterning and coloration shifts in crows.
AB  - Animal coloration is one of the most conspicuous phenotypic traits in natural
      populations and has important implications for adaptation and speciation. Changes
      in coloration can occur over surprisingly short evolutionary timescales, while
      recurrence of similar colour patterns across large phylogenetic distances is also
      common. Even though the genetic basis of pigment production is well understood,
      little is known about the mechanisms regulating colour patterning. In this study,
      we shed light on the molecular elements regulating regional pigment production in
      two genetically near-identical crow taxa with striking differences in a eumelanin
      based phenotype: black carrion and grey-coated hooded crows. We produced a high
      quality genome annotation and analysed transcriptome data from a 2 * 2 design of
      active melanogenic feather follicles from head (black in both taxa) and torso
      (black in carrion and grey in hooded crow). Extensive, parallel expression
      differences between body regions in both taxa, enriched for melanogenesis genes
      (e.g. ASIP, CORIN, and ALDH6), indicated the presence of cryptic prepatterning
      also in all-black carrion crows. Meanwhile, colour-specific expression (grey vs.
      black) was limited to a small number of melanogenesis genes in close association
      with the central transcription factor MITF (most notably HPGDS, NDP and RASGRF1).
      We conclude that colour pattern differences between the taxa likely result from
      an interaction between divergence in upstream elements of the melanogenesis
      pathway and genes that provide an underlying prepattern across the body through
      positional information. A model of evolutionary stable prepatterns that can be
      exposed and masked through simple regulatory changes may explain the
      phylogenetically independent recurrence of colour patterns that is observed
      across corvids and many other vertebrate groups. 

PMID- 26302354
TI  - Comparison of Clinician Suspicion Versus a Clinical Prediction Rule in
      Identifying Children at Risk for Intra-abdominal Injuries After Blunt Torso
      Trauma.
AB  - OBJECTIVES: Emergency department (ED) identification and radiographic evaluation
      of children with intra-abdominal injuries who need acute intervention can be
      challenging. To date, it is unclear if a clinical prediction rule is superior to
      unstructured clinician judgment in identifying these children. The objective of
      this study was to compare the test characteristics of clinician suspicion with a
      derived clinical prediction rule to identify children at risk of intra-abdominal
      injuries undergoing acute intervention following blunt torso trauma. METHODS:
      This was a planned subanalysis of a prospective, multicenter observational study
      of children (<18 years old) with blunt torso trauma conducted in 20 EDs in the
      Pediatric Emergency Care Applied Research Network (PECARN). Clinicians documented
      their suspicion for the presence of intra-abdominal injuries needing acute
      intervention as <1, 1 to 5, 6 to 10, 11 to 50, or >50% prior to knowledge of
      abdominal computed tomography (CT) scanning (if performed). Intra-abdominal
      injuries undergoing acute intervention were defined by a therapeutic laparotomy,
      angiographic embolization, blood transfusion for abdominal hemorrhage, or
      intravenous fluid administration for 2 or more days in those with pancreatic or
      gastrointestinal injuries. Patients were considered to be positive for clinician
      suspicion if suspicion was documented as >=1%. Suspicion >= 1% was compared to
      the presence of any variable in the prediction rule for identifying children with
      intra-abdominal injuries undergoing acute intervention. RESULTS: Clinicians
      recorded their suspicion in 11,919 (99%) of 12,044 patients enrolled in the
      parent study. Intra-abdominal injuries undergoing acute intervention were
      diagnosed in 203 (2%) patients. Abdominal CT scans were obtained in the ED in
      2,302 of the 2,667 (86%, 95% confidence interval [CI] = 85% to 88%) enrolled
      patients with clinician suspicion >=1% and in 3,016 of the 9,252 (33%, 95% CI =
      32% to 34%) patients with clinician suspicion < 1%. Sensitivity of the prediction
      rule for intra-abdominal injuries undergoing acute intervention (197 of 203;
      97.0%, 95% CI = 93.7% to 98.9%) was higher than that of clinician suspicion >=1%
      (168 of 203; 82.8%, 95% CI = 76.9% to 87.7%; difference = 14.2%, 95% CI = 8.6% to
      20.0%). Specificity of the prediction rule (4,979 of the 11,716; 42.5%, 95% CI =
      41.6% to 43.4%), however, was lower than that of clinician suspicion (9,217 of
      the 11,716, 78.7%, 95% CI = 77.9% to 79.4%; difference = -36.2%, 95% CI = -37.3%
      to -35.0%). Thirty-five (0.4%, 95% CI = 0.3% to 0.5%) patients with clinician
      suspicion < 1% had intra-abdominal injuries that underwent acute intervention.
      CONCLUSIONS: The derived clinical prediction rule had a significantly higher
      sensitivity, but lower specificity, than clinician suspicion for identifying
      children with intra-abdominal injuries undergoing acute intervention. The higher
      specificity of clinician suspicion, however, did not translate into clinical
      practice, as clinicians frequently obtained abdominal CT scans in patients they
      considered very low risk. If validated, this prediction rule can assist in
      clinical decision-making around abdominal CT use in children with blunt torso
      trauma.

PMID- 26302356
TI  - Human-Induced Long-Term Shifts in Gull Diet from Marine to Terrestrial Sources in
      North America's Coastal Pacific: More Evidence from More Isotopes (delta2H,
      delta34S).
AB  - Measurements of naturally occurring stable isotopes in tissues of seabirds and
      their prey are a powerful tool for investigating long-term changes in marine
      foodwebs. Recent isotopic (delta(15)N, delta(13)C) evidence from feathers of
      Glaucous-winged Gulls (Larus glaucescens) has shown that over the last 150 years,
      this species shifted from a midtrophic marine diet to one including lower trophic
      marine prey and/or more terrestrial or freshwater foods. However, long-term
      isotopic patterns of delta(15)N and delta(13)C cannot distinguish between the
      relative importance of lower trophic-level marine foods and terrestrial sources.
      We examined 48 feather stable-hydrogen (delta(2)H) and -sulfur (delta(34)S)
      isotope values from this same 150-year feather set and found additional isotopic
      evidence supporting the hypothesis that gulls shifted to terrestrial and/or
      freshwater prey. Mean feather delta(2)H and delta(34)S values (+/- SD) declined
      from the earliest period (1860-1915; n = 12) from -2.5 +/- 21.4 0/00 and 18.9 +/-
      2.7 0/00, respectively, to -35.5 +/- 15.5 0/00 and 14.8 +/- 2.4 0/00,
      respectively, for the period 1980-2009 (n = 12). We estimated a shift of ~ 30%
      increase in dependence on terrestrial/freshwater sources. These results are
      consistent with the hypothesis that gulls increased terrestrial food inputs in
      response to declining forage fish availability.

PMID- 26302357
TI  - Sonographic evaluation for intra-abdominal hemorrhage after cesarean delivery.
AB  - PURPOSE: To evaluate whether intra-abdominal hemorrhage is visible on a modified
      focused assessment with sonography for trauma (FAST) examination in stable
      obstetrics patients after a nonemergent cesarean delivery. METHODS: This was a
      prospective observational study of patients who underwent nonemergent cesarean
      delivery at a single institution. Patients provided written informed consent to
      participate in the study preoperatively and underwent a modified FAST examination
      in the recovery room within 2 hours of completion of surgery. A sonographic
      examination was considered positive for hemorrhage if an anechoic pocket
      consistent with free fluid was present. RESULTS: One hundred patients underwent
      suprapubic and bilateral upper-quadrant sonographic evaluations. The mean (+/-SD)
      time of the evaluation was 74.2 +/- 36 minutes after the end of surgery. Among
      the 100 sonographic examinations of each upper quadrant, 194 (97.0%) were
      negative, 5 (2.5%) were indeterminate, and 1 (0.5%) was positive for fluid. All
      suprapubic sonographic examinations were considered inadequate. CONCLUSIONS:
      Sonographic evaluation immediately after cesarean delivery is feasible in most
      patients and was overwhelmingly negative for intra-abdominal hemorrhage in a
      group of patients who did not require reoperation or unexpected blood
      transfusion.

PMID- 26302358
TI  - Direct Visualization of Walking Motions of Photocontrolled Nanomachine on the DNA
      Nanostructure.
AB  - A light-driven artificial molecular nanomachine was constructed based on DNA
      scaffolding. Pyrene-modified walking strands and disulfide bond-connected stator
      strands, employed as anchorage sites to support walker movement, were assembled
      into a 2D DNA tile. Pyrene molecules excited by photoirradiation at 350 nm
      induced cleavage of disulfide bond-connected stator strands, enabling the DNA
      walker to migrate from one cleaved stator to the next on the DNA tile. The time
      dependent movement of the walker was observed and the entire walking process of
      the walker was characterized by distribution of the walker-stator duplex at four
      anchorage sites on the tile under different irradiation times. Importantly, the
      light-fuelled mechanical movements on DNA tile were first visualized in real time
      during UV irradiation using high-speed atomic force microscopy (HS-AFM). 

PMID- 26302360
TI  - Characterization of monoclonal antibodies by a fast and easy liquid
      chromatography-mass spectrometry time-of-flight analysis on culture supernatant.
AB  - Rapid and efficient structural analysis is key to the development of new
      monoclonal antibodies. We have developed a fast and easy process to obtain mass
      spectrometry profiles of antibodies from culture supernatant. Treatment of the
      supernatant with IdeS generates three fragments of 25 kDa that can be analyzed by
      liquid chromatography-mass spectrometry time-of-flight (LC-MS TOF) in one run:
      LC, Fd, and Fc/2. This process gives rapid access to isoform and glycoform
      profiles. To specifically measure the fucosylation yield, we included a one-pot
      treatment with EndoS that removes the distal glycan heterogeneity. Our process
      was successfully compared with high-performance capillary electrophoresis with
      laser-induced fluorescence detection (HPCE-LIF), currently considered as the
      "gold standard" method. 

PMID- 26302359
TI  - Evaluation of changes in oral drug absorption in preterm and term neonates for
      Biopharmaceutics Classification System (BCS) class I and II compounds.
AB  - AIMS: Evidence suggests that the rate of oral drug absorption changes during
      early childhood. Yet, respective clinical implications are currently unclear,
      particularly for preterm neonates. The objective of this study was to evaluate
      changes in oral drug absorption after birth for different Biopharmaceutics
      Classification System (BCS) class I and II compounds to better understand
      respective implications for paediatric pharmacotherapy. METHODS: Two paradigm
      compounds were selected for BCS class I (paracetamol (acetaminophen) and
      theophylline) and II (indomethacin and ibuprofen), respectively, based on the
      availability of clinical literature data following intravenous and oral dosing. A
      comparative population pharmacokinetic analysis was performed in a step-wise
      manner in NONMEM(r) 7.2 to characterize and predict changes in oral drug
      absorption after birth for paracetamol, theophylline and indomethacin. RESULTS: A
      one compartment model with an age-dependent maturation function for oral drug
      absorption was found appropriate to characterize the pharmacokinetics of
      paracetamol. Our findings indicate that the rate at which a drug is absorbed from
      the GI tract reaches adult levels within about 1 week after birth. The maturation
      function for paracetamol was found applicable to theophylline and indomethacin
      once solubility limitations were overcome via drug formulation. The influence of
      excipients on solubility and, hence, oral bioavailability was confirmed for
      ibuprofen, a second BCS class II compound. CONCLUSIONS: The findings of our study
      suggest that the processes underlying changes in oral drug absorption after birth
      are drug-independent and that the maturation function identified for paracetamol
      may be generally applicable to other BCS class I and II compounds for
      characterizing drug absorption in preterm as well as term neonates.

PMID- 26302361
TI  - Upconversion luminescence resonance energy transfer-based aptasensor for the
      sensitive detection of oxytetracycline.
AB  - In this work, a biosensor based on luminescence resonance energy transfer (LRET)
      from NaYF4:Yb,Tm upconversion nanoparticles (UCNPs) to SYBR Green I has been
      developed. The aptamers are covalently linked to UCNPs and hybridized with their
      complementary strands. The subsequent addition of SYBR Green allows SYBR Green I
      to insert into the formed double-stranded DNA (dsDNA) duplex and brings the
      energy donor and acceptor into close proximity, leading to the fluorescence of
      UCNPs transferred to SYBR Green I. When excited at 980 nm, the UCNPs emit
      luminescence at 477 nm, and this energy is transferred to SYBR Green I, which
      emits luminescence at 530 nm. In the presence of oxytetracycline (OTC), the
      aptamers prefer to bind to its corresponding analyte and dehybridize with the
      complementary DNA. This dehybridization leads to the liberation of SYBR Green I,
      which distances SYBR Green I from the UCNPs and recovers the UCNPs' luminescence.
      Under optimal conditions, a linear calibration is obtained between the ratio of
      I530 to I477 nm (I530/I477) and the OTC concentration, which ranges from 0.1 to
      10 ng/ml with a limit of detection (LOD) of 0.054 ng/ml. 

PMID- 26302362
TI  - Minimizing technical variation during sample preparation prior to label-free
      quantitative mass spectrometry.
AB  - Sample preparation is the crucial starting point to obtain high-quality mass
      spectrometry data and can be divided into two main steps in a bottom-up
      proteomics approach: cell/tissue lysis with or without detergents and a(n) (in
      solution) digest comprising denaturation, reduction, alkylation, and digesting of
      the proteins. Here, some important considerations, among others, are that the
      reagents used for sample preparation can inhibit the digestion enzyme (e.g., 0.1%
      sodium dodecyl sulfate [SDS] and 0.5 M guanidine HCl), give rise to ion
      suppression (e.g., polyethylene glycol [PEG]), be incompatible with liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) (e.g., SDS), and can induce
      additional modifications (e.g., urea). Taken together, all of these
      irreproducible effects are gradually becoming a problem when label-free
      quantitation of the samples is envisioned such as during the increasingly popular
      high-definition mass spectrometry (HDMS(E)) and sequential window acquisition of
      all theoretical fragment ion spectra (SWATH) data-independent acquisition
      strategies. Here, we describe the detailed validation of a reproducible method
      with sufficient protein yield for sample preparation without any known LC-MS/MS
      interfering substances by using 1% sodium deoxycholate (SDC) during both cell
      lysis and in-solution digest. 

PMID- 26302364
TI  - Synthesis of Surface-Responsive Composite Particles by Dehydration of Water-in
      Oil Emulsions.
AB  - Organic composite particles were prepared by first emulsifying an aqueous sodium
      carboxymethyl cellulose (CMC) solution in a nonaqueous ethylcellulose (EC)
      solution, followed by dehydrating emulsified water droplets. CMC and EC are both
      biodegradable nontoxic materials, but have contrasting properties. CMC is a
      charged water-soluble polymer, while EC is an uncharged interfacially active
      water-insoluble polymer. The simple preparative method does not consume
      unnecessary chemical reagents and produces no waste material. The composite
      particles prepared by dehydrating emulsion droplets are readily dispersed in
      organic media due to its biwettable surface terminated with interfacially active
      EC molecules, which allows composite particles to preferentially adsorb at the
      oil-water droplet interface. The surface of composite particles, furthermore, is
      water-permeable, which allows water to be absorbed from emulsified droplets. The
      size, composition, and structure of the synthesized composite particles are
      ideally suited for absorption of stabilized water droplets from oil-continuous
      emulsions. The use of the composite absorbent particles, described herein,
      presents another viable strategy for dewatering water-in-oil emulsions. 

PMID- 26302363
TI  - Prospective acceleration of diffusion tensor imaging with compressed sensing
      using adaptive dictionaries.
AB  - PURPOSE: Diffusion MRI requires acquisition of multiple diffusion-weighted
      images, resulting in long scan times. Here, we investigate combining compressed
      sensing and a fast imaging sequence to dramatically reduce acquisition times in
      cardiac diffusion MRI. METHODS: Fully sampled and prospectively undersampled
      diffusion tensor imaging data were acquired in five rat hearts at acceleration
      factors of between two and six using a fast spin echo (FSE) sequence. Images were
      reconstructed using a compressed sensing framework, enforcing sparsity by means
      of decomposition by adaptive dictionaries. A tensor was fit to the reconstructed
      images and fiber tractography was performed. RESULTS: Acceleration factors of up
      to six were achieved, with a modest increase in root mean square error of mean
      apparent diffusion coefficient (ADC), fractional anisotropy (FA), and helix
      angle. At an acceleration factor of six, mean values of ADC and FA were within
      2.5% and 5% of the ground truth, respectively. Marginal differences were observed
      in the fiber tracts. CONCLUSION: We developed a new k-space sampling strategy for
      acquiring prospectively undersampled diffusion-weighted data, and validated a
      novel compressed sensing reconstruction algorithm based on adaptive dictionaries.
      The k-space undersampling and FSE acquisition each reduced acquisition times by
      up to 6* and 8*, respectively, as compared to fully sampled spin echo imaging.
      Magn Reson Med 76:248-258, 2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 26302365
TI  - Nuclear factor-kappaB pathway activation and phosphatase and tensin homolog
      downregulation in psoriasis.

PMID- 26302367
TI  - Summaries for Patients. Associations Between the Use of Low-Dose Aspirin or
      Nonsteroidal Anti-inflammatory Drugs and Colorectal Cancer Risk.

PMID- 26302366
TI  - Alleviating product inhibition in cellulase enzyme Cel7A.
AB  - Enzymes that degrade cellulose into glucose are one of the most expensive
      components of processes for converting cellulosic biomass to fuels and chemicals.
      Cellulase enzyme Cel7A is the most abundant enzyme naturally employed by fungi to
      depolymerize cellulose, and like other cellulases is inhibited by its product,
      cellobiose. There is thus great economic incentive for minimizing the detrimental
      effects of product inhibition on Cel7A. In this work, we experimentally generated
      10 previously proposed site-directed mutant Cel7A enzymes expected to have
      reduced cellobiose binding energies (the majority of mutations were to alanine).
      We then tested their resilience to cellobiose as well as their hydrolytic
      activities on microcrystalline cellulose. Although every mutation tested
      conferred reduced product inhibition (and abolished it for some), our results
      confirm a trade-off between Cel7A tolerance to cellobiose and enzymatic activity:
      Reduced product inhibition was accompanied by lower overall enzymatic activity on
      crystalline cellulose for the mutants tested. The tempering effect of mutations
      on inhibition was nearly constant despite relatively large differences in
      activities of the mutants. Our work identifies an amino acid in the Cel7A product
      binding site of interest for further mutational studies, and highlights both the
      challenge and the opportunity of enzyme engineering toward improving product
      tolerance in Cel7A.

PMID- 26302368
TI  - Red, Yellow, Green, and Blue Amplified Spontaneous Emission and Lasing Using
      Colloidal CdSe Nanoplatelets.
AB  - There have been multiple demonstrations of amplified spontaneous emission (ASE)
      and lasing using colloidal semiconductor nanocrystals. However, it has been
      proven difficult to achieve low thresholds suitable for practical use of
      nanocrystals as gain media. Low-threshold blue ASE and lasing from nanocrystals
      is an even more challenging task. Here, we show that colloidal nanoplatelets
      (NPLs) with electronic structure of quantum wells can produce ASE in the red,
      yellow, green, and blue regions of the visible spectrum with low thresholds and
      high gains. In particular, for blue-emitting NPLs, the ASE threshold is 50
      MUJ/cm(2), lower than any reported value for nanocrystals. We then demonstrate
      red, yellow, green, and blue lasing using NPLs with different thicknesses. We
      find that the lateral size of NPLs does not show any strong effect on the Auger
      recombination rates and, correspondingly, on the ASE threshold or gain
      saturation. This observation highlights the qualitative difference of
      multiexciton dynamics in CdSe NPLs and other quantum-confined CdSe materials,
      such as quantum dots and rods. Our measurements of the gain bandwidth and gain
      lifetime further support the prospects of colloidal NPLs as solution-processed
      optical gain materials. 

PMID- 26302369
TI  - The Use of Variable Q1 Isolation Windows Improves Selectivity in LC-SWATH-MS
      Acquisition.
AB  - As tryptic peptides and metabolites are not equally distributed along the mass
      range, the probability of cross fragment ion interference is higher in certain
      windows when fixed Q1 SWATH windows are applied. We evaluated the benefits of
      utilizing variable Q1 SWATH windows with regards to selectivity improvement.
      Variable windows based on equalizing the distribution of either the precursor ion
      population (PIP) or the total ion current (TIC) within each window were generated
      by an in-house software, swathTUNER. These two variable Q1 SWATH window
      strategies outperformed, with respect to quantification and identification, the
      basic approach using a fixed window width (FIX) for proteomic profiling of human
      monocyte-derived dendritic cells (MDDCs). Thus, 13.8 and 8.4% additional peptide
      precursors, which resulted in 13.1 and 10.0% more proteins, were confidently
      identified by SWATH using the strategy PIP and TIC, respectively, in the MDDC
      proteomic sample. On the basis of the spectral library purity score, some
      improvement warranted by variable Q1 windows was also observed, albeit to a
      lesser extent, in the metabolomic profiling of human urine. We show that the
      novel concept of "scheduled SWATH" proposed here, which incorporates (i) variable
      isolation windows and (ii) precursor retention time segmentation further improves
      both peptide and metabolite identifications. 

PMID- 26302370
TI  - Clinical Risk Scoring Models for Prediction of Acute Kidney Injury after Living
      Donor Liver Transplantation: A Retrospective Observational Study.
AB  - Acute kidney injury (AKI) is a frequent complication of liver transplantation and
      is associated with increased mortality. We identified the incidence and
      modifiable risk factors for AKI after living-donor liver transplantation (LDLT)
      and constructed risk scoring models for AKI prediction. We retrospectively
      reviewed 538 cases of LDLT. Multivariate logistic regression analysis was used to
      evaluate risk factors for the prediction of AKI as defined by the RIFLE criteria
      (RIFLE = risk, injury, failure, loss, end stage). Three risk scoring models were
      developed in the retrospective cohort by including all variables that were
      significant in univariate analysis, or variables that were significant in
      multivariate analysis by backward or forward stepwise variable selection. The
      risk models were validated by way of cross-validation. The incidence of AKI was
      27.3% (147/538) and 6.3% (34/538) required postoperative renal replacement
      therapy. Independent risk factors for AKI by multivariate analysis of forward
      stepwise variable selection included: body-mass index >27.5 kg/m2 [odds ratio
      (OR) 2.46, 95% confidence interval (CI) 1.32-4.55], serum albumin <3.5 mg/dl (OR
      1.76, 95%CI 1.05-2.94), MELD (model for end-stage liver disease) score >20 (OR
      2.01, 95%CI 1.17-3.44), operation time >600 min (OR 1.81, 95%CI 1.07-3.06), warm
      ischemic time >40 min (OR 2.61, 95%CI 1.55-4.38), postreperfusion syndrome (OR
      2.96, 95%CI 1.55-4.38), mean blood glucose during the day of surgery >150 mg/dl
      (OR 1.66, 95%CI 1.01-2.70), cryoprecipitate > 6 units (OR 4.96, 95%CI 2.84-8.64),
      blood loss/body weight >60 ml/kg (OR 4.05, 95%CI 2.28-7.21), and calcineurin
      inhibitor use without combined mycophenolate mofetil (OR 1.87, 95%CI 1.14-3.06).
      Our risk models performed better than did a previously reported score by Utsumi
      et al. in our study cohort. Doses of calcineurin inhibitor should be reduced by
      combined use of mycophenolate mofetil to decrease postoperative AKI. Prospective
      randomized trials are required to address whether artificial modification of
      hypoalbuminemia, hyperglycemia and postreperfusion syndrome would decrease
      postoperative AKI in LDLT. 

PMID- 26302372
TI  - Stereochemical Investigation of the Products of the Photoinduced
      Perfluoroalkylation-Dimerization of Anthracene.
AB  - The photoinduced perfluoroalkylation of anthracene has been shown to provide
      9,9',10,10'-tetrahydro-10,10'-diperfluoroalkyl-9,9'-bianthracenes in over 70%
      yields, each perfluoroalkyl iodide producing three diastereomers. The structures
      of all three diastereomers (cis,cis, cis,trans, and trans,trans isomers) have
      been elucidated by both NMR and X-ray crystallographic analyses. Most notably, an
      X-ray crystallographic analysis has revealed that the trans,trans diastereomer
      having the two trifluoromethyl groups in 10,10'-positions adopts a 74 degrees 
      twisted relationship of the two dihydroanthracene rings. Furthermore, each of the
      two trans,trans isomers 2a,b has been shown to exist as a mixture of new types of
      atropisomers and the energy barrier for the interconversion of the two
      atropisomers has been estimated to be 12 kcal/mol by variable-temperature NMR
      analysis. 

PMID- 26302371
TI  - A Stable Lipid/TiO2 Interface with Headgroup-Inversed Phosphocholine and a
      Comparison with SiO2.
AB  - Zwitterionic phosphocholine (PC) lipids are highly biocompatible, representing a
      major component of the cell membrane. A simple mixing of PC liposomes and silica
      (SiO2) surface results in liposome fusion with the surface and formation of
      supported lipid bilayers. However, the stability of this bilayer is relatively
      low because adsorption is based mainly on weak van der Waals force. PC lipids
      strongly adsorb by TiO2 via chemical bonding with the lipid phosphate. The lack
      of fusion on TiO2 is attributable to the steric effect from the choline group in
      PC. In this study, inverse phosphocholine lipids (CP) are used, directly exposing
      the phosphate. Using a calcein leakage assay and cryo-TEM, fusion of CP liposome
      with TiO2 is demonstrated. The stability of this supported bilayer is
      significantly higher than that of the PC/SiO2 system, as indicated by washing the
      membrane under harsh conditions. Adsorption of CP liposomes by TiO2 is inhibited
      at high pH. Interestingly, the CP liposome cannot fuse with silica surface
      because of a strong charge repulsion. This study demonstrates an interesting
      interplay between a soft matter surface and metal oxides. By tuning the lipid
      structure, it is possible to rationally control the interaction force. This study
      provides an alternative system for forming stable supported bilayers on TiO2, and
      represents the first example of interfacing inverse lipids with inorganic
      surfaces. 

PMID- 26302373
TI  - Variables Associated with Infections of Cattle by Brucella abortus., Leptospira
      spp. and Neospora spp. in Amazon Region in Brazil.
AB  - The frequency of Neospora spp., Leptospira spp. and Brucella abortus infections
      in adult cattle was determined in herds of the State of Para, Brazil, which is an
      important region for cattle production located in the Amazon region. A total of
      3466 adult female cattle from 176 herds were tested, leading to a frequency of
      seropositive animals of 14.7%, 3.7% and 65.5% and a herd positivity of 87.4%,
      41.3% and 98.8% for infections caused by Neospora spp., B. abortus and Leptospira
      spp., respectively. The five most frequently diagnosed serologic responses to
      Leptospira spp. were those against serovars hardjo, wolfii, grippotyphosa,
      hebdomadis and shermani. The following associations were found: practice of
      artificial insemination, large farm size, large herd size, large number of dogs
      and high number of total abortions per year with the presence of antibodies
      against serovar hardjo; positive results to serovar grippotyphosa with the
      presence of dogs; inappropriate disposal of aborted foetuses with positivity to
      serovar hebdomadis. Serovar grippotyphosa was also associated with number of
      episodes of abortions. Neospora spp. positive herds were associated with episodes
      of abortion and B. abortus infection with the disposal of dead animals and
      aborted foetuses on pastures and with the use of artificial insemination. In
      conclusion, the high frequency of brucellosis, leptospirosis and neosporosis in
      the region may be a consequence of social, natural and raising conditions as: (i)
      climate conditions that favour the survival and spread of pathogens in the
      environment; (ii) farms located in regions bordering forest areas; (iii) farms in
      areas of difficult access to the veterinary service; (iv) extensive beef herds
      raised at pastures with different age and productive groups inter-mingled; and
      (v) minimal concerns regarding hygiene practices and disease prevention measures.

PMID- 26302374
TI  - The Effect of Prenatal and Childhood Development on Hearing, Vision and Cognition
      in Adulthood.
AB  - It is unclear what the contribution of prenatal versus childhood development is
      for adult cognitive and sensory function and age-related decline in function. We
      examined hearing, vision and cognitive function in adulthood according to self
      reported birth weight (an index of prenatal development) and adult height (an
      index of early childhood development). Subsets (N = 37,505 to 433,390) of the UK
      Biobank resource were analysed according to visual and hearing acuity, reaction
      time and fluid IQ. Sensory and cognitive performance was reassessed after ~4
      years (N = 2,438 to 17,659). In statistical modelling including age, sex,
      socioeconomic status, educational level, smoking, maternal smoking and comorbid
      disease, adult height was positively associated with sensory and cognitive
      function (partial correlations; pr 0.05 to 0.12, p < 0.001). Within the normal
      range of birth weight (10th to 90th percentile), there was a positive association
      between birth weight and sensory and cognitive function (pr 0.06 to 0.14, p <
      0.001). Neither adult height nor birth weight was associated with change in
      sensory or cognitive function. These results suggest that adverse prenatal and
      childhood experiences are a risk for poorer sensory and cognitive function and
      earlier development of sensory and cognitive impairment in adulthood. This
      finding could have significant implications for preventing sensory and cognitive
      impairment in older age. 

PMID- 26302375
TI  - Single-Cell Genetic Analysis Using Automated Microfluidics to Resolve Somatic
      Mosaicism.
AB  - Somatic mosaicism occurs throughout normal development and contributes to
      numerous disease etiologies, including tumorigenesis and neurological disorders.
      Intratumor genetic heterogeneity is inherent to many cancers, creating challenges
      for effective treatments. Unfortunately, analysis of bulk DNA masks subclonal
      phylogenetic architectures created by the acquisition and distribution of somatic
      mutations amongst cells. As a result, single-cell genetic analysis is becoming
      recognized as vital for accurately characterizing cancers. Despite this, methods
      for single-cell genetics are lacking. Here we present an automated microfluidic
      workflow enabling efficient cell capture, lysis, and whole genome amplification
      (WGA). We find that ~90% of the genome is accessible in single cells with
      improved uniformity relative to current single-cell WGA methods. Allelic dropout
      (ADO) rates were limited to 13.75% and variant false discovery rates (SNV FDR)
      were 4.11x10(-6), on average. Application to ER-/PR-/HER2+ breast cancer cells
      and matched normal controls identified novel mutations that arose in a
      subpopulation of cells and effectively resolved the segregation of known cancer
      related mutations with single-cell resolution. Finally, we demonstrate effective
      cell classification using mutation profiles with 10X average exome coverage depth
      per cell. Our data demonstrate an efficient automated microfluidic platform for
      single-cell WGA that enables the resolution of somatic mutation patterns in
      single cells.

PMID- 26302376
TI  - Evaluating the real-world predictive validity of the Body Image Quality of Life
      Inventory using Ecological Momentary Assessment.
AB  - Perceptions of physical appearance, or body image, can affect psychosocial
      functioning and quality of life (QOL). The present study evaluated the real-world
      predictive validity of the Body Image Quality of Life Inventory (BIQLI) using
      Ecological Momentary Assessment (EMA). College women reporting subclinical
      disordered eating/body dissatisfaction (N=131) completed the BIQLI and related
      measures. For one week they then completed five daily EMA surveys of mood, social
      interactions, stress, and eating behaviors on palmtop computers. Results showed
      better body image QOL was associated with less negative affect, less overwhelming
      emotions, more positive affect, more pleasant social interactions, and higher
      self-efficacy for handling stress. Lower body image QOL was marginally related to
      less overeating and lower loss of control over eating in daily life. To our
      knowledge, this is the first study to support the real-world predictive validity
      of the BIQLI by identifying social, affective, and behavioral correlates in
      everyday life using EMA. 

PMID- 26302378
TI  - DNA sequence context greatly affects the accuracy of bypass across an ultraviolet
      light 6-4 photoproduct in mammalian cells.
AB  - Translesion DNA synthesis (TLS) is a DNA damage tolerance mechanism carried out
      by low-fidelity DNA polymerases that bypass DNA lesions, which overcomes
      replication stalling. Despite the miscoding nature of most common DNA lesions,
      several of them are bypassed in mammalian cells in a relatively accurate manner,
      which plays a key role maintaining a low mutation load. Whereas it is generally
      agreed that TLS across the major UV and sunlight induced DNA lesion, the
      cyclobutane pyrimidine dimer (CPD), is accurate, there were conflicting reports
      on whether the same is true for the thymine-thymine pyrimidine-pyrimidone(6-4)
      ultraviolet light photoproduct (TT6-4PP), which represents the second most common
      class of UV lesions. Using a TLS assay system based on gapped plasmids carrying
      site-specific TT6-4PP lesions in defined sequence contexts we show that the DNA
      sequence context markedly affected both the extent and accuracy of TLS. The
      sequence exhibiting higher TLS exhibited also higher error-frequency, caused
      primarily by semi-targeted mutations, at the nearest nucleotides flanking the
      lesion. Our results resolve the discrepancy reported on TLS across TT6-4PP, and
      suggest that TLS is more accurate in human cells than in mouse cells. 

PMID- 26302379
TI  - The key role of miR-21-regulated SOD2 in the medium-mediated bystander responses
      in human fibroblasts induced by alpha-irradiated keratinocytes.
AB  - Radiation-induced bystander effect (RIBE) is well accepted in the radiation
      research field by now, but the underlying molecular mechanisms for better
      understanding this phenomenon caused by intercellular communication and
      intracellular signal transduction are still incomplete. Although our previous
      study has demonstrated an important role of miR-21 of unirradiated bystander
      cells in RIBEs, the direct evidence for the hypothesis that RIBE is
      epigenetically regulated is still limited and how miR-21 mediates RIBEs is
      unknown. Reactive oxygen species (ROS) have been demonstrated to be involved in
      RIBEs, however, the roles of anti-oxidative stress system of cells in RIBEs are
      unclear. Using transwell insert co-culture system, we investigated medium
      mediated bystander responses in WS1 human fibroblasts after co-culture with HaCaT
      keratinocytes traversed by alpha-particles. Results showed that the ROS levels in
      unirradiated bystander WS1 cells were significantly elevated after 30min of co
      culture, and 53BP1 foci, a surrogate marker of DNA damage, were obviously induced
      after 3h of co-culture. This indicates the occurrence of oxidative stress and DNA
      damage in bystander WS1 cells after co-culture with irradiated keratinocytes.
      Furthermore, the expression of miR-21 was increased in bystander WS1 cells,
      downregulation of miR-21 eliminated the bystander responses, overexpression of
      miR-21 alone could induce bystander-like oxidative stress and DNA damage in WS1
      cells. These data indicate an important mediating role of miR-21 in RIBEs. In
      addition, MnSOD or SOD2 in WS1 cells was involved in the bystander effects,
      overexpression of SOD2 abolished the bystander oxidative stress and DNA damage,
      indicating that SOD2 was critical to the induction of RIBEs. Moreover, we found
      that miR-21 regulated SOD2, suggesting that miR-21 might mediate bystander
      responses through its regulation on SOD2. In conclusion, this study revealed a
      profound role of miR-21-regulated SOD2 of unirradiated WS1 cells in bystander
      effects induced by alpha-irradiated HaCaT keratinocytes. 

PMID- 26302381
TI  - Heat-shock protein expression in canine corneal wound healing.
AB  - OBJECTIVE: Heat-shock proteins, particularly the 70-kDa member (Hsp70), have been
      implicated in facilitating wound healing in multiple tissues. Expression and
      localization of three HSPs were assessed in normal and wounded canine corneas to
      elucidate a role in epithelial healing. METHODS: Paraffin-embedded normal
      corneas, acute and repeatedly abraded corneas, and keratectomies of spontaneous
      chronic corneal epithelial defects (SCCEDs) were subjected to routine
      immunohistochemistry for Hsp27, 47, and 70 expression. Ex vivo corneal defects
      were created and treated with anti-HSPs or IgG controls, and wound healing was
      monitored. Primary cultures of canine corneal stromal fibroblasts and corneal
      epithelial cells were treated with exogenous Hsp70, and an artificial wound was
      created in vitro to monitor restoration of the monolayer. RESULTS: Normal canine
      corneas exhibited constitutive expression of all HSPs evaluated. Inducible
      expression was demonstrated in acutely wounded tissues, and expression in the
      chronically abraded corneas was relocalized. All HSP expression was below the
      limits of detection in the epithelium of SCCED samples. Inhibition of HSPs in
      culture resulted in delayed wound healing when compared to controls. Hsp70
      treated fibroblasts demonstrated significantly (P < 0.001) increased migration
      and proliferation compared to the vehicle control; however, there was no
      significant effect of exogenous Hsp70 on corneal epithelial cells. CONCLUSIONS:
      These findings suggest that HSPs are induced in the normal canine cornea during
      re-epithelialization. Hsp70 expression is likely important for inducing the
      cytoarchitectural remodeling, migration, and proliferation necessary early in the
      canine corneal healing response, and suppressed expression may contribute to the
      pathophysiology of nonhealing defects.

PMID- 26302380
TI  - Short-term Forecasting of the Prevalence of Trachoma: Expert Opinion, Statistical
      Regression, versus Transmission Models.
AB  - BACKGROUND: Trachoma programs rely on guidelines made in large part using expert
      opinion of what will happen with and without intervention. Large community
      randomized trials offer an opportunity to actually compare forecasting methods in
      a masked fashion. METHODS: The Program for the Rapid Elimination of Trachoma
      trials estimated longitudinal prevalence of ocular chlamydial infection from 24
      communities treated annually with mass azithromycin. Given antibiotic coverage
      and biannual assessments from baseline through 30 months, forecasts of the
      prevalence of infection in each of the 24 communities at 36 months were made by
      three methods: the sum of 15 experts' opinion, statistical regression of the
      square-root-transformed prevalence, and a stochastic hidden Markov model of
      infection transmission (Susceptible-Infectious-Susceptible, or SIS model). All
      forecasters were masked to the 36-month results and to the other forecasts.
      Forecasts of the 24 communities were scored by the likelihood of the observed
      results and compared using Wilcoxon's signed-rank statistic. FINDINGS: Regression
      and SIS hidden Markov models had significantly better likelihood than community
      expert opinion (p = 0.004 and p = 0.01, respectively). All forecasts scored
      better when perturbed to decrease Fisher's information. Each individual expert's
      forecast was poorer than the sum of experts. INTERPRETATION: Regression and SIS
      models performed significantly better than expert opinion, although all forecasts
      were overly confident. Further model refinements may score better, although would
      need to be tested and compared in new masked studies. Construction of guidelines
      that rely on forecasting future prevalence could consider use of mathematical and
      statistical models. TRIAL REGISTRATION: Clinicaltrials.gov NCT00792922.

PMID- 26302383
TI  - The emergence of commodity-scale genetic manipulation.
AB  - Since the 1970s technological advancements in the fields of synthetic biology and
      metabolic engineering have led to a dramatic reduction in both time and cost
      required for generating genomic mutations in a variety of organisms. The union of
      genomic editing machinery, DNA inkjet printers, and bioinformatics algorithms
      allows engineers to design a library of thousands of unique oligos as well as
      build and test these designs on a ~2 months time-scale and at a cost of roughly
      ~0.3 cents per base pair. The implications of these capabilities for a variety of
      fields are far-reaching, with potential impacts in defense, agricultural, human
      health, and environmental research. The explosion of synthetic biology
      applications over the past two decades have led many to draw parallels between
      biological engineering and the computer sciences. In this review, we highlight
      some important parallels between these fields and emphasize the importance of
      engineering design strategies. 

PMID- 26302382
TI  - Prophylactic Injection of Recombinant Alpha-Enolase Reduces Arthritis Severity in
      the Collagen-Induced Arthritis Mice Model.
AB  - OBJECTIVE: To evaluate the ability of the glycolytic enzyme alpha-enolase (ENO1)
      or its immunodominant peptide (pEP1) to reduce the severity of CIA in DBA/1 mice
      when injected in a prophylactic way. METHODS: Mice were treated with mouse ENO1
      or pEP1 one day prior to collagen II immunization. Clinical assessment was
      evaluated using 4 parameters (global and articular scores, ankle thickness and
      weight). Titers of serum anti-ENO1, anti-cyclic citrullinated peptides (anti-CCP)
      and anti-CII (total IgG and IgG1/IgG2a isotypes) antibodies were measured by
      ELISA at different time-points. Disease activity was assessed by histological
      analysis of both anterior and hind paws at the end of experimentation. RESULTS:
      Prophylactic injection of 100 MUg of ENO1 reduced severity of CIA. Serum levels
      of anti-CII antibodies were reduced in ENO1-treated mice. Concordantly, ENO1
      treated mice joints presented less severe histological signs of arthritis. ENO1
      did not induce a shift toward a Th2 response since IgG1/IgG2a ratio of anti-CII
      antibodies remained unchanged and IL-4 serum levels were similar to those
      measured in the control group. CONCLUSIONS: Pre-immunization with ENO1 or its
      immunodominant peptide pEP1 reduces CIA severity at the clinical, immunological
      and histological levels. Effects of pEP1 were less pronounced. This
      immunomodulatory effect is associated with a reduction in anti-CII antibodies
      production but is not due to a Th1/Th2 shift.

PMID- 26302384
TI  - Genetic code expansion enabled site-specific dual-color protein labeling:
      superresolution microscopy and beyond.
AB  - Genetic code expansion is emerging as an important tool for manipulation and
      labeling of proteins in vitro and in vivo. In combination with click-chemistry it
      allows site-specific labeling of target proteins with small organic fluorophores.
      This is achieved by cotranslational incorporation of noncanonical amino acids
      (ncAAs) in target proteins via orthogonal tRNA/amino-acyl tRNA synthetase pairs.
      In a subsequent step, ncAAs are labeled with small dyes via click-chemistry.
      Small labeling tags and free choice of which fluorophore to use and where to put
      it into the protein are of particular importance for single molecule science and
      superresolution microscopy. Such genetically encoded click chemistry tools
      facilitate high resolution studies of protein function in live cells, viral
      imaging, as well as the improved design of antibody-drug conjugates. 

PMID- 26302385
TI  - Science to Practice: Molecularly Targeted US of Inflammation-Important Steps
      toward Clinical Translation.
AB  - Dual P- and E-selectin-targeted microbubbles (MBs) have previously been used for
      ultrasonography (US) of acute inflammatory bowel disease in mice. In the study by
      Wang and colleagues, such dual-targeted MBs were evaluated in pigs. After
      induction of ileitis by means of 2, 4, 6-trinitrobenzene sulfonic acid
      (TNBS)/ethanol installation, early inflammation, as well as mild and severe
      disease stages, could be distinguished. The molecularly targeted US method was
      characterized by high reproducibility and matched with histologic findings. This
      work is considered an important intermediate step in translating molecularly
      targeted US of inflammation from preclinical toward clinical application. 

PMID- 26302386
TI  - The RSNA Editorial Fellows: Then and Now.
AB  - Since its establishment in 1998, the Radiological Society of North America (RSNA)
      Editorial Fellowship has been offering unique opportunities to radiologists from
      around the world who have a strong interest in radiologic journalism. For the
      past 16 years, the selected RSNA Editorial Fellows have learned essential
      processes involved in the production of Radiology and RadioGraphics by working
      closely with the editors, associate editors, and staff. The editorial fellowship
      for radiology attending physicians was renamed the RSNA William R. Eyler
      Editorial Fellowship, in honor of the founding editor of RadioGraphics, with the
      first Eyler fellow selected in 2005. Additionally, several years ago, a second
      fellowship was created for radiology trainees, which is now named the RSNA
      William W. Olmsted Editorial Fellowship for Trainees, in honor of the most recent
      emeritus editor of RadioGraphics. For the special centennial year of the journal
      Radiology, several former editorial fellows were interested in knowing what the
      previous fellows are up to presently and how their experience and learning from
      the fellowship influenced and contributed to their academic career development.
      The invitation to share their experience of the RSNA Editorial Fellowship was
      sent to 19 previous RSNA Editorial Fellows. We report the findings from 16 of
      these fellows who responded. We found that almost all previous RSNA Editorial
      Fellows (15 of 16, 94%) stayed in academic radiology, and each is currently
      leading a successful academic career. All of them are currently actively serving
      in one or more positions as an editor, associate editor, reviewer, and/or
      editorial board member of various radiology journals and clinical journals
      related to their area(s) of academic expertise. Among the 16 previous editorial
      fellows who responded, there are four chairs and six vice-chairs of their
      respective radiology departments. All of them reported that the experience and
      knowledge they gained from the RSNA Editorial Fellowship was crucial for their
      academic and professional development. Their views on the experience of being an
      RSNA Editorial Fellow, accomplishments achieved after the fellowship, and current
      activities are included here.

PMID- 26302387
TI  - Radiology in the Lion City.

PMID- 26302389
TI  - Imaging Review of the Temporal Bone: Part II. Traumatic, Postoperative, and
      Noninflammatory Nonneoplastic Conditions.
AB  - The first part of this review of the temporal bone discussed anatomy of the
      temporal bone as well as inflammatory and neoplastic processes in the temporal
      bone region (1). This second part will first discuss trauma to the temporal bone
      and posttraumatic complications. The indications for common surgical procedures
      performed in the temporal bone and their postoperative imaging appearance are
      then presented. Finally, a few noninflammatory nonneoplastic entities involving
      the temporal bone are reviewed. They are relatively uncommon diagnoses compared
      with infectious or inflammatory diseases. However, because patients present with
      symptoms that are either common (hearing loss) or distinctive (sensorineural
      hearing loss in a child), they are important for the radiologist to be aware of
      and recognize.

PMID- 26302388
TI  - Dual- and Multi-Energy CT: Principles, Technical Approaches, and Clinical
      Applications.
AB  - In x-ray computed tomography (CT), materials having different elemental
      compositions can be represented by identical pixel values on a CT image (ie, CT
      numbers), depending on the mass density of the material. Thus, the
      differentiation and classification of different tissue types and contrast agents
      can be extremely challenging. In dual-energy CT, an additional attenuation
      measurement is obtained with a second x-ray spectrum (ie, a second "energy"),
      allowing the differentiation of multiple materials. Alternatively, this allows
      quantification of the mass density of two or three materials in a mixture with
      known elemental composition. Recent advances in the use of energy-resolving,
      photon-counting detectors for CT imaging suggest the ability to acquire data in
      multiple energy bins, which is expected to further improve the signal-to-noise
      ratio for material-specific imaging. In this review, the underlying motivation
      and physical principles of dual- or multi-energy CT are reviewed and each of the
      current technical approaches is described. In addition, current and evolving
      clinical applications are introduced.

PMID- 26302393
TI  - Case 221: Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome.
AB  - History A 24-year-old woman presented to the emergency department with a history
      of acute urinary retention, gross hematuria, and left flank pain for 2 days. Past
      history was unrevealing. Her last menstrual period occurred 2 weeks prior to
      presentation. At physical examination, she had a temperature of 38.4 degrees C. A
      palpable mass was noted in the suprapubic region, and a second mass was palpated
      in the left upper quadrant. Blood work revealed a hemoglobin level of 4.7 g/dL
      (normal range, 11.5-15.5 g/dL). Her coagulation profile and white blood cell
      count were within normal limits. Ultrasonography (US) of the abdomen and pelvis
      was performed and was followed by contrast material-enhanced (80 mL of iopamidol)
      computed tomography (CT) of the chest, abdomen, and pelvis. Magnetic resonance
      (MR) imaging of the abdomen and pelvis also was performed. 

PMID- 26302394
TI  - Shear-wave Elastography for the Noninvasive Diagnosis of Focal Liver Lesions: It
      Always Starts with the Clinical Context.

PMID- 26302395
TI  - Malpractice and Public Policy: Are they Separable?

PMID- 26302396
TI  - Integrity of Data in a Randomized Controlled Trial.

PMID- 26302397
TI  - Aggressive Intrasegmental Recurrence of Periportal Hepatocellular Carcinoma after
      Radiofrequency Ablation: Role of Ablative Technique and Heat-Sink Effect?

PMID- 26302401
TI  - Monitoring of Yeast Communities and Volatile Flavor Changes During Traditional
      Korean Soy Sauce Fermentation.
AB  - Flavor development in soy sauce is significantly related to the diversity of
      yeast species. Due to its unique fermentation with meju, the process of making
      Korean soy sauce gives rise to a specific yeast community and, therefore, flavor
      profile; however, no detailed analysis of the identifying these structure has
      been performed. Changes in yeast community structure during Korean soy sauce
      fermentation were examined using both culture-dependent and culture-independent
      methods with simultaneous analysis of the changes in volatile compounds by GC-MS
      analysis. During fermentation, Candida, Pichia, and Rhodotorula sp. were the
      dominant species, whereas Debaryomyces, Torulaspora, and Zygosaccharomyces sp.
      were detected only at the early stage. In addition, Cryptococcus, Microbotryum,
      Tetrapisispora, and Wickerhamomyces were detected as minor strains. Among the 62
      compounds identified in this study, alcohols, ketones, and pyrazines were present
      as the major groups during the initial stages, whereas the abundance of acids
      with aldehydes increased as the fermentation progressed. Finally, the impacts of
      10 different yeast strains found to participate in fermentation on the formation
      of volatile compounds were evaluated under soy-based conditions. It was revealed
      that specific species produced different profiles of volatile compounds, some of
      which were significant flavor contributors, especially volatile alcohols,
      aldehydes, esters, and ketones. 

PMID- 26302400
TI  - Increased Circulating Cathepsin K in Patients with Chronic Heart Failure.
AB  - Cysteinyl cathepsin K (CatK) is one of the most potent mammalian collagenases
      involved in cardiovascular disease. Here, we investigated the clinical predictive
      value of serum CatK levels in patients with chronic heart failure (CHF). We
      examined 134 patients with CHF, measuring their serum CatK, troponin I, high
      sensitive C-reactive protein, and pre-operative N-terminal pro-brain natriuretic
      peptide levels. The patients were divided into two groups: the 44 patients who
      showed a left ventricular (LV) ejection fraction (LVEF) < 40% (the "lowLVEF"
      group) and the 90 patients showing LVEF values >= 40% (the "highLVEF" group). The
      lowLVEF patients had significantly higher serum CatK levels compared to the
      highLVEF patients (58.4 +/- 12.2 vs. 44.7 +/- 16.4, P < 0.001). Overall, a linear
      regression analysis showed that CatK levels correlated negatively with LVEF (r = 
      0.4, P < 0.001) and positively with LV end-diastolic dimensions (r = 0.2, P <
      0.01), LV end-systolic dimensions (r = 0.3, P < 0.001), and left atrial diameters
      (r = 0.3, P < 0.01). A multiple logistic regression analysis showed that CatK
      levels were independent predictors of CHF (odds ratio, 0.90; 95% confidence
      interval, 0.84-0.95; P < 0.01). These data indicate that elevated levels of CatK
      are closely associated with the presence of CHF and that the measurement of
      circulating CatK provides a noninvasive method of documenting and monitoring the
      extent of cardiac remodeling and dysfunction in patients with CHF. 

PMID- 26302402
TI  - Why Small Differences Matter: Elucidation of the Mechanisms Underlying the
      Transformation of 2OH- and 3OH-Carbamazepine in Contact with Sand Filter
      Material.
AB  - Carbamazepine (CBZ) is a worldwide used antiepileptic drug, which is metabolized
      to a large extent in the human body to several metabolites, including 10,11
      dihydroxy-10,11-dihydrocarbamazepine (DiOHCBZ), 2-hydroxycarbamazepine (2OHCBZ),
      and 3-hydroxycarbamazepine (3OHCBZ). 2OHCBZ and 3OHCBZ were previously detected
      in raw and treated wastewater revealing their widespread emission into the
      aquatic environment, eventually leading to the contamination of drinking water
      resources. Sand filtration is frequently applied in drinking water treatment for
      the removal of inorganic species and suspended particles but has been shown to be
      capable of removing trace organic contaminants. This study focuses on the
      elucidation of the (bio)transformation mechanisms of 2OHCBZ and 3OHCBZ in contact
      with material taken from a rapid sand filter of a German waterworks. Despite
      their similar structure, which differs only in the position of the phenolic OH
      moiety, both compounds underwent distinct transformation reactions leading to the
      formation of a variety of transformation products (TPs). The main biochemical
      reactions thereby included enzymatic transformation of 2OHCBZ resulting in the
      formation of a reactive iminoquinone intermediate (2OHCBZ) and nitration via
      peroxynitrite (2OHCBZ and 3OHCBZ) as well as formation of radicals leading to
      dimerization (3OHCBZ). Further transformation reactions included hydroxylation,
      ring cleavage, loss of carbamoyl group, and decarboxylation, as well as O
      methylation. 

PMID- 26302403
TI  - Whole Course Neuroendoscopic Resection of Cerebellopontine Angle Epidermoid
      Cysts.
AB  - Background Epidermoid cysts are the third most common tumor of the
      cerebellopontine angle (CPA). Diagnosis often occurs after involvement of the
      sulci and cisterns that surround nerves and blood vessels, making complete
      resection highly challenging. Objective To determine the efficacy of whole course
      neuroendoscopic surgery in the management of CPA epidermoid cysts. Methods We
      performed a retrospective analysis of clinical data of 13 male and 17 female
      patients (mean age: 42.4 +/- 11.4 years) who presented with a CPA epidermoid cyst
      and underwent whole course neuroendoscopy. Complications and tumor recurrence
      were assessed at follow-up. Results Clinical manifestations included an initial
      symptom of headache (n = 21), gait instability (n = 6), intracranial hypertension
      (n = 13), posterior cranial nerve symptoms (n = 6), ataxia (n = 5), and
      hydrocephalus (n = 1). All patients tolerated tumor resection with subsequent
      symptomatic improvement, and the results of the postoperative magnetic resonance
      imaging scan did not show any remnants of tumor. Mean duration of surgery was
      2.61 +/- 0.47 hours, mean loss of blood was 96.8 +/- 35.4 mL, and the mean
      duration of hospitalization was 7.5 +/- 2.25 days. Postoperative complications (8
      of 30 [26.7%]) included fever (n = 5), communicating hydrocephalus (n = 1),
      facial nerve paralysis (n = 1), and abducens nerve palsy (n = 1). Tumor
      recurrence was observed in two patients (6.7%). No deaths or intracranial
      hemorrhage was reported. Conclusions The characteristics of epidermoid cysts make
      them amenable to whole course neuroendoscopic resection. Use of
      physiologic/pathologic interspaces and neuroendoscopic angulations decreases
      traction on the brain, improves complete resection rates, and decreases
      postoperative complications. 

PMID- 26302404
TI  - Endoscopic Biopsy for Intra- and Paraventricular Tumors: Rates of Complications,
      Mortality, and Tumor Cell Dissemination.
AB  - BACKGROUND AND STUDY AIM: Intra- and paraventricular tumors are frequently
      associated with cerebrospinal fluid (CSF) pathway obstruction. Thus the aim of an
      endoscopic approach is to restore patency of the CSF pathways and to obtain a
      tumor biopsy. Because endoscopic tumor biopsy may increase tumor cell
      dissemination, this study sought to evaluate this risk. PATIENTS, MATERIALS, AND
      METHODS: Forty-four patients who underwent endoscopic biopsies for ventricular or
      paraventricular tumors between 1993 and 2011 were included in the study. Charts
      and images were reviewed retrospectively to evaluate rates of adverse events,
      mortality, and tumor cell dissemination. Adverse events, mortality, and tumor
      cell dissemination were evaluated. RESULTS: Postoperative clinical condition
      improved in 63.0% of patients, remained stable in 30.4%, and worsened in 6.6%.
      One patient (2.2%) had a postoperative thalamic stroke leading to hemiparesis and
      hemineglect. No procedure-related deaths occurred. Postoperative tumor cell
      dissemination was observed in 14.3% of patients available for follow-up.
      CONCLUSIONS: For patients presenting with occlusive hydrocephalus due to tumors
      in or adjacent to the ventricular system, endoscopic CSF diversion is the
      procedure of first choice. Tumor biopsy in the current study did not affect
      safety or efficacy.

PMID- 26302406
TI  - Distinct E-cadherin-based complexes regulate cell behaviour through miRNA
      processing or Src and p120 catenin activity.
AB  - E-cadherin and p120 catenin (p120) are essential for epithelial homeostasis, but
      can also exert pro-tumorigenic activities. Here, we resolve this apparent paradox
      by identifying two spatially and functionally distinct junctional complexes in
      non-transformed polarized epithelial cells: one growth suppressing at the apical
      zonula adherens (ZA), defined by the p120 partner PLEKHA7 and a non-nuclear
      subset of the core microprocessor components DROSHA and DGCR8, and one growth
      promoting at basolateral areas of cell-cell contact containing tyrosine
      phosphorylated p120 and active Src. Recruitment of DROSHA and DGCR8 to the ZA is
      PLEKHA7 dependent. The PLEKHA7-microprocessor complex co-precipitates with
      primary microRNAs (pri-miRNAs) and possesses pri-miRNA processing activity.
      PLEKHA7 regulates the levels of select miRNAs, in particular processing of miR
      30b, to suppress expression of cell transforming markers promoted by the
      basolateral complex, including SNAI1, MYC and CCND1. Our work identifies a
      mechanism through which adhesion complexes regulate cellular behaviour and
      reveals their surprising association with the microprocessor. 

PMID- 26302409
TI  - Autophagy in the lens.
AB  - The lens of the eye is a transparent tissue composed of lens fiber cells that
      differentiate from lens epithelial cells and degrade all cytoplasmic organelles
      during terminal differentiation. Autophagy is a major intracellular degradation
      system in which cytoplasmic proteins and organelles are degraded in the lysosome.
      Although autophagy is constitutively activated in the lens and has been proposed
      to be involved in lens organelle degradation, its precise role is not well
      understood. Recent genetic studies in mice have demonstrated that autophagy is
      critically important for intracellular quality control in the lens but can be
      dispensable for lens organelle degradation. Here, we review recent findings on
      the roles of autophagy and lysosomes in organelle degradation and intracellular
      quality control in the lens, and discuss their possible involvement in the
      development of human cataract. 

PMID- 26302408
TI  - Pyruvate carboxylation enables growth of SDH-deficient cells by supporting
      aspartate biosynthesis.
AB  - Succinate dehydrogenase (SDH) is a heterotetrameric nuclear-encoded complex
      responsible for the oxidation of succinate to fumarate in the tricarboxylic acid
      cycle. Loss-of-function mutations in any of the SDH genes are associated with
      cancer formation. However, the impact of SDH loss on cell metabolism and the
      mechanisms enabling growth of SDH-defective cells are largely unknown. Here, we
      generated Sdhb-ablated kidney mouse cells and used comparative metabolomics and
      stable-isotope-labelling approaches to identify nutritional requirements and
      metabolic adaptations to SDH loss. We found that lack of SDH activity commits
      cells to consume extracellular pyruvate, which sustains Warburg-like bioenergetic
      features. We further demonstrated that pyruvate carboxylation diverts glucose
      derived carbons into aspartate biosynthesis, thus sustaining cell growth. By
      identifying pyruvate carboxylase as essential for the proliferation and
      tumorigenic capacity of SDH-deficient cells, this study revealed a metabolic
      vulnerability for potential future treatment of SDH-associated malignancies. 

PMID- 26302410
TI  - Defects in autophagy caused by glaucoma-associated mutations in optineurin.
AB  - Certain mutations in optineurin (gene OPTN) are associated with primary open
      angle glaucoma. Optineurin is ubiquitously expressed but it shows high level of
      expression in certain cells and tissues including retinal ganglion cells. It
      interacts with many proteins, often acting as an adaptor to link two or more
      proteins. These interactions play a crucial role in mediating various functions
      of optineurin such as membrane vesicle trafficking, autophagy, signal
      transduction etc. Autophagy is basically a quality control mechanism to remove
      damaged proteins and organelles through lysosomal degradation. Optineurin was
      identified as an autophagy receptor that directly interacts with autophagosomal
      protein, LC3, and ubiquitin. These interactions are important for autophagy
      receptor function. Autophagy receptors recruit their cargo and take it to
      autophagosomes which fuse with lysosomes to form autolysosomes where degradation
      of proteins takes place. Optineurin interacts with a motor protein, myosinVI, and
      this interaction is involved in mediating fusion of autophagosomes with
      lysosomes. A glaucoma-associated mutant of optineurin, E50K, impairs autophagy as
      well as vesicle trafficking, leading to death of retinal cells by apoptosis. E50K
      OPTN-induced block in autophagy is dependent on a GTPase activating protein,
      TBC1D17. The E50K mutant also causes other changes in the cells such as altered
      interaction with TBK1 protein kinase, aggregate formation, generation of reactive
      oxygen species and inhibition of proteasome, which may contribute to
      pathogenesis. A polymorphism of optineurin, M98K, associated with glaucoma,
      causes enhanced autophagy leading to transferrin receptor degradation and
      apoptotic death of retinal cells. M98K-OPTN-induced autophagic cell death is
      dependent on Rab12 GTPase. Thus, an optimum level of optineurin-mediated
      autophagy is crucial for survival of retinal cells, and impaired autophagy is
      likely to contribute to glaucoma pathogenesis. How impaired autophagy caused by
      optineurin mutants leads to apoptosis and cell death, is yet to be explored. 

PMID- 26302412
TI  - Evolution of cognition.
AB  - Renewed interest in the field of comparative cognition over the past 30 years has
      led to a renaissance in our thinking of how cognition evolved. Here, we review
      historical and comparative approaches to the study of psychological evolution,
      focusing on cognitive differences based on evolutionary divergence, but also
      cognitive similarities based on evolutionary convergence. Both approaches have
      contributed to major theories of cognitive evolution in humans and non-human
      animals. As a result, not only have we furthered our understanding of the
      evolution of the human mind and its unique attributes, but we have also
      identified complex cognitive capacities in a few large-brained species, evolved
      from solving social and ecological challenges requiring a flexible mind. WIREs
      Cogni Sci 2011 2 621-633 DOI: 10.1002/wcs.144 For further resources related to
      this article, please visit the WIREs website. 

PMID- 26302407
TI  - Combined CSL and p53 downregulation promotes cancer-associated fibroblast
      activation.
AB  - Stromal fibroblast senescence has been linked to ageing-associated cancer risk.
      However, density and proliferation of cancer-associated fibroblasts (CAFs) are
      frequently increased. Loss or downmodulation of the Notch effector CSL (also
      known as RBP-Jkappa) in dermal fibroblasts is sufficient for CAF activation and
      ensuing keratinocyte-derived tumours. We report that CSL silencing induces
      senescence of primary fibroblasts from dermis, oral mucosa, breast and lung. CSL
      functions in these cells as a direct repressor of multiple senescence- and CAF
      effector genes. It also physically interacts with p53, repressing its activity.
      CSL is downmodulated in stromal fibroblasts of premalignant skin actinic
      keratosis lesions and squamous cell carcinomas, whereas p53 expression and
      function are downmodulated only in the latter, with paracrine FGF signalling as
      the probable culprit. Concomitant loss of CSL and p53 overcomes fibroblast
      senescence, enhances expression of CAF effectors and promotes stromal and cancer
      cell expansion. The findings support a CAF activation-stromal co-evolution model
      under convergent CSL-p53 control. 

PMID- 26302413
TI  - Number words, quantifiers, and principles of word learning.
AB  - How do children learn the meanings of words like many and five? Although much is
      known about the mechanisms that underlie children's acquisition of nouns and
      verbs, considerably less is understood of how children begin to learn the
      meanings of words that refer to sets (e.g., number words and quantifiers). Here
      we argue that children's acquisition of quantity expressions relies on learning
      mechanisms typically associated with learning content words. In particular, we
      argue that the Whole Object Assumption and the Principle of Contrast are special
      cases of more general principles that guide not just the acquisition of nouns and
      verbs, but also the acquisition and interpretation of number words and
      quantifiers. WIREs Cogni Sci 2011 2 639-645 DOI: 10.1002/wcs.140 For further
      resources related to this article, please visit the WIREs website. 

PMID- 26302411
TI  - Targeting the ER-autophagy system in the trabecular meshwork to treat glaucoma.
AB  - A major drainage network involved in aqueous humor dynamics is the conventional
      outflow pathway, which is gated by the trabecular meshwork (TM). The TM acts as a
      molecular sieve, providing resistance to aqueous outflow, which is responsible
      for regulating intraocular pressure (IOP). If the TM is damaged, aqueous outflow
      is impaired, IOP increases and glaucoma can manifest. Mutations in the MYOC gene
      cause hereditary primary open-angle glaucoma (POAG) by promoting the abnormal
      amyloidosis of the myocilin protein in the endoplasmic reticulum (ER), leading to
      ER stress-induced TM cell death. Myocilin accumulation is observed in
      approximately 70-80% of all glaucoma cases suggesting that environmental or other
      genetic factors may also promote myocilin toxicity. For example, simply
      preventing myocilin glycosylation is sufficient to promote its abnormal
      accretion. These myocilin amyloids are unique as there are no other known
      pathogenic proteins that accumulate within the ER of TM cells and cause toxicity.
      Moreover, this pathogenic accumulation only kills TM cells, despite expression of
      this protein in other cell types, suggesting that another modifier exclusive to
      the TM participates in the proteotoxicity of myocilin. ER autophagy
      (reticulophagy) is one of the pathways essential for myocilin clearance that can
      be impacted dramatically by aging and other environmental factors such as
      nutrition. This review will discuss the link between myocilin and autophagy,
      evaluating the role of this degradation pathway in glaucoma as well as its
      potential as a therapeutic target. 

PMID- 26302415
TI  - Neural basis of affect and emotion.
AB  - Research on affect and emotion has recently been informed by novel methods and
      theories in cognitive neuroscience. This perspective, known as affective
      neuroscience, has the potential to dramatically improve our understanding of
      fundamental processes of emotion. In this article, we review the major neural
      systems involved in emotion and consider the computational properties of these
      regions. Specifically, we consider affect systems associated with the
      representation of predicted and experienced affective states, the cortical re
      representation of body states, and the role of reflection in generating and
      maintaining emotional episodes. WIREs Cogni Sci 2011 2 656-665 DOI:
      10.1002/wcs.145 For further resources related to this article, please visit the
      WIREs website. 

PMID- 26302414
TI  - Informal learning.
AB  - We consider research and theory relevant to the notion of informal learning.
      Beginning with historical and definitional issues, we argue that learning happens
      not just in schools or in school-aged children. Many theorists have contrasted
      informal learning with formal learning. Moving beyond this dichotomy, and away
      from a focus on where learning occurs, we discuss five dimensions of informal
      learning that are drawn from the literature: (1) non-didactive, (2) highly
      socially collaborative, (3) embedded in meaningful activity, (4) initiated by
      learner's interest or choice, and (5) removed from external assessment. We
      consider these dimensions in the context of four sample domains: learning a first
      language, learning about the mind and emotions within families and communities,
      learning about science in family conversations and museum settings, and workplace
      learning. Finally, we conclude by considering convergences and divergences across
      the different literatures and suggesting areas for future research. WIREs Cogni
      Sci 2011 2 646-655 DOI: 10.1002/wcs.143 For further resources related to this
      article, please visit the WIREs website. 

PMID- 26302416
TI  - Sociolinguistic variables and cognition.
AB  - Sociolinguistics has examined mental organization of language only sporadically.
      Meanwhile, areas of linguistics that deal with cognitive organization seldom
      delve deeply into language variation. Variation is essential for understanding
      how language is structured cognitively, however. Three kinds of evidence are
      discussed to illustrate this point. First, style shifting demonstrates that
      language users develop detailed associations of when to produce specific
      linguistic forms, depending on the pragmatic context. Second, variation in fine
      grained phonetic cues shows that cognitive organization applies to linguistic
      forms not otherwise known to be under speakers' control. Finally, experiments on
      dialect comprehension and identification demonstrate that listeners have detailed
      cognitive associations of language variants with groups of people, whether or not
      they can produce the same variants themselves. A model is presented for how
      sociolinguistic knowledge can be viewed in relation to other parts of language
      with regard to cognitive and neural representations. WIREs Cogni Sci 2011 2 701
      716 DOI: 10.1002/wcs.152 For further resources related to this article, please
      visit the WIREs website. 

PMID- 26302417
TI  - Electrochemical Investigations of 4-Methoxypyridine Adsorption on Au(111) Predict
      Its Suitability for Stabilizing Au Nanoparticles.
AB  - A thermodynamic analysis of the adsorption of 4-methoxypyridine (MOP) on Au(111)
      surfaces is presented in an effort to determine its propensity to stabilize metal
      nanoparticles. The adsorption of MOP is compared and contrasted to the adsorption
      of 4-dimethylaminopyridine (DMAP), the latter of which is well-known to form
      stable Au nanoparticles. Electrochemical studies show that MOP, like most
      pyridine derivatives, can exhibit two different adsorption states. The electrical
      state of the metal, the pH of the solution, and the surface crystallography
      determine whether MOP adopts a low-coverage, pi-bonded orientation or a high
      coverage, sigma-type orientation. A modified Langmuir adsorption isotherm is used
      to extract free energies of adsorption which are roughly 10% stronger for DMAP
      compared to MOP at equivalent conditions when expressed on a rational basis. The
      higher adsorption strength is attributed to DMAP's greater Lewis basicity.
      Qualitatively, MOP and DMAP adsorption are found to be completely analogous,
      implying that MOP-protected gold particles should be stable under conditions that
      favor the high-coverage adsorption state. Using a previously reported, single
      phase synthesis, this is shown to be the case. 

PMID- 26302418
TI  - Redox-Noninnocent Behavior of Tris(2-pyridylmethyl)amine Bound to a Lewis Acidic
      Rh(III) Ion Induced by C-H Deprotonation.
AB  - Rh(III) complexes having tris(2-pyridylmethyl)amine (TPA) and its derivative as
      tetradentate ligands showed reversible deprotonation at a methylene moiety of the
      TPA ligands upon addition of a strong base as confirmed by spectroscopic
      measurements and X-ray crystallography. Deprotonation selectively occurred at the
      axial methylene moiety rather than equatorial counterparts because of the
      thermodynamic stability of corresponding deprotonated complexes. One-electron
      oxidation of the deprotonated Rh(III)-TPA complex afforded a unique TPA radical
      bound to the Rh(III) center by a ligand-centered oxidation. This is the first
      example to demonstrate emergence of the redox-noninnocent character of the TPA
      ligand. 

PMID- 26302419
TI  - Assessment of a novel overflow-type electrochemical membrane bioreactor (EMBR)
      for wastewater treatment, energy recovery and membrane fouling mitigation.
AB  - A novel overflow-type electrochemical membrane bioreactor (EMBR) without ion
      exchange membrane, was developed for wastewater treatment and utilized
      electricity recovered by microbial fuel cell (MFC) for membrane fouling
      mitigation in membrane bioreactor (MBR). The maximum power density of 629mW/m(3)
      or 7.18mW/m(2) was obtained. The removal efficiencies of chemical oxygen demand,
      ammonia nitrogen and total nitrogen under appropriate ranges of hydraulic
      retention times (16.9-8.5h) were 92.6+/-5.4%, 96.5+/-2.8% and 73.9+/-9.7%,
      respectively. Sequencing showed electrochemically active bacteria Lactococcus,
      Bacillus and Saprospiraceae_uncultured were abundant in the biofilm. Compared
      with a conventional MBR, five significant effects of the MFC integration on the
      sludge properties, including particle zeta potential decrease, particle size
      distribution macroaggregation, soluble microbial products and extracellular
      polymeric substances reduction and SMPP/SMPC ratio increase, were achieved in
      this system, leading to membrane fouling mitigation. This system shows great
      promise for practical wastewater treatment application.

PMID- 26302420
TI  - Proteomic Analysis of Disease Stratified Human Pancreas Tissue Indicates Unique
      Signature of Type 1 Diabetes.
AB  - Type 1 diabetes (T1D) and type 2 diabetes (T2D) are associated with functional
      beta cell loss due to ongoing inflammation. Despite shared similarities, T1D is
      an autoimmune disease with evidence of autoantibody production, as well as a role
      for exocrine pancreas involvement. Our hypothesis is that differential protein
      expression occurs in disease stratified pancreas tissues and regulated proteins
      from endocrine and exocrine tissues are potential markers of disease and
      potential therapeutic targets. The study objective was to identify novel proteins
      that distinguish the pancreas from donors with T1D from the pancreas from
      patients with T2D, or autoantibody positive non-diabetic donors. Detailed
      quantitative comprehensive proteomic analysis was applied to snap frozen human
      pancreatic tissue lysates from organ donors without diabetes, with T1D-associated
      autoantibodies in the absence of diabetes, with T1D, or with T2D. These disease
      stratified human pancreas tissues contain exocrine and endocrine tissues (with
      dysfunctional islets) in the same microenvironment. The expression profiles of
      several of the proteins were further verified by western blot. We identified
      protein panels that are significantly and uniquely upregulated in the three
      disease-stratified pancreas tissues compared to non-disease control tissues.
      These proteins are involved in inflammation, metabolic regulation, and
      autoimmunity, all of which are pathways linked to, and likely involved in, T1 and
      T2 diabetes pathogenesis. Several new proteins were differentially upregulated in
      prediabetic, T1D, and T2D pancreas. The results identify proteins that could
      serve as novel prognostic, diagnostic, and therapeutic tools to preserve
      functional islet mass in Type 1 Diabetes. 

PMID- 26302423
TI  - The Pain Pendulum Swinging Again.

PMID- 26302421
TI  - Engineering Metamorphic Chemokine Lymphotactin/XCL1 into the GAG-Binding, HIV
      Inhibitory Dimer Conformation.
AB  - Unlike other chemokines, XCL1 undergoes a distinct metamorphic interconversion
      between a canonical monomeric chemokine fold and a unique beta-sandwich dimer.
      The monomeric conformation binds and activates the receptor XCR1, whereas the
      dimer binds extracellular matrix glycosaminoglycans and has been associated with
      anti-human immunodeficiency virus (HIV) activity. Functional studies of WT-XCL1
      are complex, as both conformations are populated in solution. To overcome this
      limitation, we engineered a stabilized dimeric variant of XCL1 designated CC5.
      This variant features a new disulfide bond (A36C-A49C) that prevents structural
      interconversion by locking the chemokine into the beta-sandwich dimeric
      conformation, as demonstrated by NMR structural analysis and hydrogen/deuterium
      exchange experiments. Functional studies analyzing glycosaminoglycan binding
      demonstrate that CC5 binds with high affinity to heparin. In addition, CC5
      exhibits potent inhibition of HIV-1 activity in primary peripheral blood
      mononuclear cells (PBMCs), demonstrating the importance of the dimer in blocking
      viral infection. Conformational variants like CC5 are valuable tools for
      elucidating the biological relevance of the XCL1 native-state interconversion and
      will assist in future antiviral and functional studies. 

PMID- 26302424
TI  - Response to "We Haven't Got a Prayer".

PMID- 26302425
TI  - Do Palliative Care Clinics Screen for Substance Abuse and Diversion? Results of a
      National Survey.
AB  - BACKGROUND: Opioids are the mainstay of treatment of cancer pain. With increased
      use there have been concerns about rising rates of prescription drug abuse and
      diversion. Although there has been an increase in research and practice
      guidelines about the scope of the problem for chronic, nonmalignant pain, less
      information is available about both the frequency of the problem and current
      practices regarding screening for substance abuse and diversion in patients and
      family members seen in palliative care clinics. OBJECTIVE: The aim of this study
      was to evaluate the degree to which palliative programs felt that substance abuse
      and diversion was an issue, and to identify practices regarding care of patients
      with potential substance misuse issues. METHODS: We sent a survey regarding
      substance abuse perception, policies, training, and screening to 94 accredited
      palliative medicine fellowship program directors as obtained by the Accreditation
      Council for Graduate Medical Education (ACGME) directory. RESULTS: We received
      usable responses from 38 (40.4%) programs. Policies for screening patients
      (40.5%) or family members (16.2%), dealing with diversion (27%), and use of a
      screening tool (32.4%) were reported infrequently. Despite this, one-half of
      respondents indicated that substance abuse and diversion was an issue for their
      clinics, with only 25% indicating substance abuse was not an issue. Additionally,
      the majority of fellows (83%) and about half (47%) of staff received mandatory
      training for dealing with substance misuse. All programs provided some screening
      of patients, with 48.7% screening all patients for abuse. Screening of family
      members was relatively rare, as was routine use of the urine drug screen (UDS).
      CONCLUSION: Despite increased concerns about substance abuse, the majority of
      programs did not have substance abuse and diversion policies or report screening
      all patients, with screening of caregivers rarely reported. Consensus guidelines
      addressing substance abuse and diversion for palliative patients are needed to
      address this growing problem.

PMID- 26302426
TI  - The Evolution and Dissemination of the Education in Palliative and End-of-Life
      Care Program.
AB  - BACKGROUND: Even with growing numbers of fellowship-trained palliative care
      providers, primary palliative care knowledge and skills are needed to meet the
      national demands for palliative care. The Education in Palliative and End-of-Life
      Care (EPEC) Program has been one model of training clinicians in primary
      palliative care skills. In our second 5 years of development and dissemination,
      we have focused on adapting EPEC to different specialties. OBJECTIVE: Our aim was
      to describe the development of EPEC adaptations and document the dissemination of
      our curriculum. METHODS: The study design was a survey of EPEC trainers and
      documentation of other dissemination efforts via literature and Internet
      searches. Our subjects were all EPEC trainers and end-learners of our curriculum.
      We measured dissemination and teaching efforts by our trainers and evidence of
      EPEC use via literature and EPEC's searches. RESULTS: In Internet second 5 years
      of active development, teaching, and dissemination, we have created five major
      adaptations (EPEC-Oncology, EPEC-Oncology-Canada, EPEC-Emergency Medicine, EPEC
      India, and EPEC for Veterans) and trained more than 1000 trainers. Through the
      efforts of these Trainers and our online dissemination, more than 74,000 reported
      end-learners have been taught parts of the EPEC curriculum. In addition, we
      discovered multiple medical school courses, continuing medical education (CME),
      courses and specialty guidelines that have incorporated material from EPEC.
      CONCLUSIONS: In its second 5 years, EPEC remains a robust platform for adaptation
      to new specialties and for dissemination of primary palliative care knowledge.

PMID- 26302427
TI  - Subjective Dyspnea.

PMID- 26302428
TI  - Young drivers' responses to anti-speeding advertisements: Comparison of self
      report and objective measures of persuasive processing and outcomes.
AB  - OBJECTIVE: Self-report measures are typically used to assess the effectiveness of
      road safety advertisements. However, psychophysiological measures of persuasive
      processing (i.e., skin conductance response [SCR]) and objective driving measures
      of persuasive outcomes (i.e., in-vehicle Global Positioning System [GPS] devices)
      may provide further insights into the effectiveness of these advertisements. This
      study aimed to explore the persuasive processing and outcomes of 2 anti-speeding
      advertisements by incorporating both self-report and objective measures of
      speeding behavior. In addition, this study aimed to compare the findings derived
      from these different measurement approaches. METHODS: Young drivers (N = 20, M
      age = 21.01 years) viewed either a positive or negative emotion-based anti
      speeding television advertisement. While viewing the advertisement, SCR activity
      was measured to assess ad-evoked arousal responses. The RoadScout GPS device was
      then installed in participants' vehicles for 1 week to measure on-road speed
      related driving behavior. Self-report measures assessed persuasive processing
      (emotional and arousal responses) and actual driving behavior. RESULTS: There was
      general correspondence between the self-report measures of arousal and the SCR
      and between the self-report measure of actual driving behavior and the objective
      driving data (as assessed via the GPS devices). CONCLUSIONS: This study provides
      insights into how psychophysiological and GPS devices could be used as objective
      measures in conjunction with self-report measures to further understand the
      persuasive processes and outcomes of emotion-based anti-speeding advertisements.

PMID- 26302429
TI  - Management of d-PTFE Membrane Exposure for Having Final Clinical Success.

PMID- 26302430
TI  - Preference for Condoms, Antiretroviral Preexposure Prophylaxis, or Both Methods
      to Reduce Risk for HIV Acquisition Among Uninfected US Black and Latino MSM.

PMID- 26302431
TI  - Using Molecular HIV Surveillance Data to Understand Transmission Between
      Subpopulations in the United States.
AB  - BACKGROUND: Studying HIV transmission networks provides insight into the spread
      of HIV and opportunities for intervention. We identified transmission dynamics
      among risk groups and racial/ethnic groups in the United States. METHODS: For HIV
      1 pol sequences reported to the US National HIV Surveillance System during 2001
      2012, we calculated pairwise genetic distance, identified linked pairs of
      sequences (those with distance <=1.5%), and examined transmission category and
      race/ethnicity of these potential transmission partners. RESULTS: Of 40,950
      sequences, 12,910 (32%) were linked to >=1 other sequence. Of men who have sex
      with men (MSM) who were linked to >=1 sequence, 88% were linked to other MSM and
      only 4% were linked to heterosexual women. Of heterosexual women for whom we
      identified potential transmission partners, 29% were linked to MSM, 21% to
      heterosexual men, and 12% to persons who inject drugs. Older and black MSM were
      more likely to be linked to heterosexual women. Assortative mixing was present
      for all racial/ethnic groups; 81% of blacks/African Americans linked to other
      blacks. CONCLUSIONS: This analysis is the first use of US surveillance data to
      infer an HIV transmission network. Our data suggest that HIV infections among
      heterosexual women predominantly originate from MSM, followed by heterosexual
      men. Although few MSM were linked to women, suggesting that a minority of MSM are
      involved in transmission with heterosexual women, these transmissions represent a
      substantial proportion of HIV acquisitions by heterosexual women. Interventions
      that reduce transmissions involving MSM are likely to also reduce HIV acquisition
      among other risk groups.

PMID- 26302432
TI  - Latex Rubber Gloves as a Sampling Dosimeter Using a Novel Surrogate Sampling
      Device.
AB  - Pesticide exposure during harvesting of crops occurs primarily to the workers'
      hands. When harvesters wear latex rubber gloves for personal safety and hygiene
      harvesting reasons, gloves accumulate pesticide residues. Hence, characterization
      of the gloves' properties may be useful for pesticide exposure assessments.
      Controlled field studies were conducted using latex rubber gloves to define the
      factors that influence the transfer of pesticides to the glove and that would
      affect their use as a residue monitoring device. A novel sampling device called
      the Brinkman Contact Transfer Unit (BCTU) was constructed to study the glove
      characteristics and residue transfer and accumulation under controlled conditions
      on turf. The effectiveness of latex rubber gloves as sampling dosimeters was
      evaluated by measuring the transferable pesticide residues as a function of time.
      The validation of latex rubber gloves as a residue sampling dosimeter was
      performed by comparing pesticide transfer and dissipation from the gloves, with
      the turf transferable residues sampled using the validated California (CA)
      Roller, a standard measure of residue transfer. The observed correlation
      (Pearson's correlation coefficient R(2)) between the two methods was .84 for
      malathion and .96 for fenpropathrin, indicating that the BCTU is a useful,
      reliable surrogate tool for studying available residue transfer to latex rubber
      gloves under experimental conditions. Perhaps more importantly, these data
      demonstrate that latex gloves worn by workers may be useful quantifiable matrices
      for measuring pesticide exposure. 

PMID- 26302433
TI  - Positive selection underlies the species-specific binding of Plasmodium
      falciparum RH5 to human basigin.
AB  - Plasmodium falciparum, the causative agent of the deadliest form of malaria, is a
      member of the Laverania subgenus, which includes ape-infecting parasites. P.
      falciparum is thought to have originated in gorillas, although infection is now
      restricted to humans. Laverania parasites display remarkable host-specificity,
      which is partially mediated by the interaction between parasite ligands and host
      receptors. We analyse the evolution of BSG (basigin) and GYPA (glycophorin A) in
      primates/hominins, as well as of their Plasmodium-encoded ligands, PfRH5 and
      PfEBA175. We show that, in primates, positive selection targeted two sites in BSG
      (F27 and H102), both involved in PfRH5 binding. A population genetics
      phylogenetics approach detected the strongest selection for the gorilla lineage:
      one of the positively selected sites (K191) is a major determinant of PfRH5
      binding affinity. Analysis of RH5 genes indicated episodic selection on the P.
      falciparum branch; the positively selected W447 site is known to stabilize the
      interaction with human basigin. Conversely, we detect no selection in the
      receptor-binding region of EBA175 in the P. falciparum lineage. Its host
      receptor, GYPA, shows evidence of positive selection in all hominid lineages;
      selected codons include glycosylation sites that modulate PfEBA175 binding
      affinity. Data herein provide an evolutionary explanation for species-specific
      binding of the PfRH5-BSG ligand-receptor pair and support the hypothesis that
      positive selection at these genes drove the host shift leading to the emergence
      of P. falciparum as a human pathogen. 

PMID- 26302434
TI  - The interaction of testosterone and cortisol is associated with attained status
      in male executives.
AB  - Are hormone levels associated with the attainment of social status? Although
      endogenous testosterone predicts status-seeking social behaviors, research
      suggests that the stress hormone cortisol may inhibit testosterone's effects.
      Thus, individuals with both high testosterone and low cortisol may be especially
      likely to occupy high-status positions in social hierarchies while individuals
      with high testosterone and high cortisol may not. We tested this hypothesis by
      recruiting a sample of real executives and examining testosterone, cortisol, and
      a concrete indicator of attained status: the number of subordinates over which
      the executive has authority. Despite the myriad nonhormonal factors that
      determine organizational promotion, the executives' endogenous testosterone and
      cortisol interacted to significantly predict hierarchical position: Testosterone
      positively predicted executives' number of subordinates, but only among low
      cortisol executives. The results imply that reducing cortisol levels via stress
      reduction may be a critical goal not only because doing so will improve health
      but also because doing so may enhance leadership potential. (PsycINFO Database
      Record 

PMID- 26302435
TI  - Squeezed in the middle: The middle status trade creativity for focus.
AB  - Classical research on social influence suggested that people are the most
      conforming in the middle of a status hierarchy as opposed to the top or bottom.
      Yet this promising line of research was abandoned before the psychological
      mechanism behind middle-status conformity had been identified. Moving beyond the
      early focus on conformity, we propose that the threat of status loss may make
      those with middle status more wary of advancing creative solutions in fear that
      they will be evaluated negatively. Using different manipulations of status and
      measures of creativity, we found that when being evaluated, middle-status
      individuals were less creative than either high-status or low-status individuals
      (Studies 1 and 2). In addition, we found that anxiety at the prospect of status
      loss also caused individuals with middle status to narrow their focus of
      attention and to think more convergently (Study 3). We delineate the consequences
      of power and status both theoretically and empirically by showing that, unlike
      status, the relationship between power and creativity is positive and linear
      (Study 4). By both measuring status (Studies 2 and 3) and by manipulating it
      directly (Study 5), we demonstrate that the threat of status loss explains the
      consequences of middle status. Finally, we discuss the theoretical implications
      of our results for future research on status and problem solving on tasks that
      require either focus or flexibility.

PMID- 26302436
TI  - Conceptualizing psychological processes in response to globalization: Components,
      antecedents, and consequences of global orientations.
AB  - The influences of globalization have permeated various aspects of life in
      contemporary society, from technical innovations, economic development, and
      lifestyles, to communication patterns. The present research proposed a construct
      termed global orientation to denote individual differences in the psychological
      processes of acculturating to the globalizing world. It encompasses multicultural
      acquisition as a proactive response and ethnic protection as a defensive response
      to globalization. Ten studies examined the applicability of global orientations
      among majority and minority groups, including immigrants and sojourners, in
      multicultural and relatively monocultural contexts, and across Eastern and
      Western cultures. Multicultural acquisition is positively correlated with both
      independent and interdependent self-construals, bilingual proficiency and usage,
      and dual cultural identifications. Multicultural acquisition is promotion
      focused, while ethnic protection is prevention-focused and related to
      acculturative stress. Global orientations affect individuating and modest
      behavior over and above multicultural ideology, predict overlap with outgroups
      over and above political orientation, and predict psychological adaptation,
      sociocultural competence, tolerance, and attitudes toward ethnocultural groups
      over and above acculturation expectations/strategies. Global orientations also
      predict English and Chinese oral presentation performance in multilevel analyses
      and the frequency and pleasantness of intercultural contact in cross-lagged panel
      models. We discuss how the psychological study of global orientations contributes
      to theory and research on acculturation, cultural identity, and intergroup
      relations.

PMID- 26302438
TI  - Use of a Bidentate Ligand Featuring an N-Heterocyclic Phosphenium Cation (NHP(+))
      to Systematically Explore the Bonding of NHP(+) Ligands with Nickel.
AB  - A novel bidentate ligand featuring an N-heterocyclic phosphenium cation (NHP(+))
      linked to a phosphine side arm is used to explore the coordination chemistry of
      NHP(+) ligands with nickel. Direct P-Cl bond cleavage from a chlorophosphine
      precursor [PP]-Cl (1) by Ni(COD)2 affords the asymmetric bimetallic complex
      [Cl2Ni(MU-PP)2Ni] (2) via a nonoxidative process. Abstraction of the halide with
      either NaBPh4 or K[B(C6F5)4] prior to metal coordination to form the free
      phosphenium ligand [PP](+) in situ, followed by coordination to Ni(COD)2,
      afforded the halide-free Ni(0) complexes [(PP)Ni(COD)] [B(C6F5)4] (4) and
      [(PP)Ni(COD)][BPh4] (5). Chloride abstraction from 1 is problematic in the
      presence of a PF6(-) counterion, however, as evident by the formation of
      [(PP)Ni(PP-F)][PF6] (3). The COD ligand in 5 can be readily displaced with PMe3
      or PPh3 to afford [(PP)NiL2][BPh4] (L = PMe3 (6), PPh3 (7)). Complexes 2-7
      feature planar geometries about the NHP(+) phosphorus atom and unusually short Ni
      P distances, indicative of multiple bonding resulting from both P -> Ni sigma
      donation and Ni -> P pi backbonding. This bonding description is supported by
      theoretical studies using natural bond orbital analysis. 

PMID- 26302437
TI  - Treating disorders of the neonatal central nervous system: pharmacokinetic and
      pharmacodynamic considerations with a focus on antiepileptics.
AB  - A major consideration in the treatment of neonatal disorders is that the selected
      drug, dose and dosage frequency is safe, effective and appropriate for the
      intended patient population. Thus, a thorough knowledge of the pharmacokinetics
      and pharmacodynamics of the chosen drug within the patient population is
      essential. In paediatric and neonatal populations two additional challenges can
      often complicate drug treatment - the inherently greater physiological
      variability, and a lack of robust clinical evidence of therapeutic range. There
      has traditionally been an overreliance in paediatric medicine on extrapolating
      doses from adult values by adjusting for bodyweight or body surface area, but
      many other sources of variability exist which complicate the choice of dose in
      neonates. The lack of reliable drug dosage data in neonates has been highlighted
      by regulatory authorities, as only ~50% of the most commonly used paediatric
      medicines have been examined in a paediatric population. Moreover, there is a
      paucity of information on the pharmacokinetic parameters which affect drug
      concentrations in different body tissues, and pharmacodynamic responses to drugs
      in the neonate. Thus, in the present review, we draw attention to the main
      pharmacokinetic factors that influence the unbound brain concentration of
      neuroactive drugs. Moreover, the pharmacodynamic differences between neonates and
      adults that affect the activity of centrally-acting therapeutic agents are
      briefly examined, with a particular emphasis on antiepileptic drugs. 

PMID- 26302439
TI  - Nerve Growth Factor Gene Therapy: Activation of Neuronal Responses in Alzheimer
      Disease.
AB  - IMPORTANCE: Alzheimer disease (AD) is the most common neurodegenerative disorder
      and lacks effective disease-modifying therapies. In 2001, we initiated a clinical
      trial of nerve growth factor (NGF) gene therapy in AD, the first effort at gene
      delivery in an adult neurodegenerative disorder. This program aimed to determine
      whether a nervous system growth factor prevents or reduces cholinergic neuronal
      degeneration in patients with AD. We present postmortem findings in 10 patients
      with survival times ranging from 1 to 10 years after treatment. OBJECTIVE: To
      determine whether degenerating neurons in AD retain an ability to respond to a
      nervous system growth factor delivered after disease onset. DESIGN, SETTING, AND
      PARTICIPANTS: Patients in this anatomicopathological study were enrolled in
      clinical trials from March 2001 to October 2012 at the University of California,
      San Diego, Medical Center in La Jolla. Ten patients with early AD underwent NGF
      gene therapy using ex vivo or in vivo gene transfer. The brains of all 8 patients
      in the first phase 1 ex vivo trial and of 2 patients in a subsequent phase 1 in
      vivo trial were examined. MAIN OUTCOMES AND MEASURES: Brains were immunolabeled
      to evaluate in vivo gene expression, cholinergic neuronal responses to NGF, and
      activation of NGF-related cell signaling. In 2 patients, NGF protein levels were
      measured by enzyme-linked immunosorbent assay. RESULTS: Among 10 patients,
      degenerating neurons in the AD brain responded to NGF. All patients exhibited a
      trophic response to NGF in the form of axonal sprouting toward the NGF source.
      Comparing treated and nontreated sides of the brain in 3 patients who underwent
      unilateral gene transfer, cholinergic neuronal hypertrophy occurred on the NGF
      treated side (P < .05). Activation of cellular signaling and functional markers
      was present in 2 patients who underwent adeno-associated viral vectors (serotype
      2)-mediated NGF gene transfer. Neurons exhibiting tau pathology and neurons free
      of tau expressed NGF, indicating that degenerating cells can be infected with
      therapeutic genes, with resultant activation of cell signaling. No adverse
      pathological effects related to NGF were observed. CONCLUSIONS AND RELEVANCE:
      These findings indicate that neurons of the degenerating brain retain the ability
      to respond to growth factors with axonal sprouting, cell hypertrophy, and
      activation of functional markers. Sprouting induced by NGF persists for 10 years
      after gene transfer. Growth factor therapy appears safe over extended periods and
      merits continued testing as a means of treating neurodegenerative disorders.

PMID- 26302440
TI  - Spatio-temporal Genetic Structuring of Leishmania major in Tunisia by
      Microsatellite Analysis.
AB  - In Tunisia, cases of zoonotic cutaneous leishmaniasis caused by Leishmania major
      are increasing and spreading from the south-west to new areas in the center. To
      improve the current knowledge on L. major evolution and population dynamics, we
      performed multi-locus microsatellite typing of human isolates from Tunisian
      governorates where the disease is endemic (Gafsa, Kairouan and Sidi Bouzid
      governorates) and collected during two periods: 1991-1992 and 2008-2012. Analysis
      (F-statistics and Bayesian model-based approach) of the genotyping results of
      isolates collected in Sidi Bouzid in 1991-1992 and 2008-2012 shows that, over two
      decades, in the same area, Leishmania parasites evolved by generating genetically
      differentiated populations. The genetic patterns of 2008-2012 isolates from the
      three governorates indicate that L. major populations did not spread gradually
      from the south to the center of Tunisia, according to a geographical gradient,
      suggesting that human activities might be the source of the disease expansion.
      The genotype analysis also suggests previous (Bayesian model-based approach) and
      current (F-statistics) flows of genotypes between governorates and districts.
      Human activities as well as reservoir dynamics and the effects of environmental
      changes could explain how the disease progresses. This study provides new
      insights into the evolution and spread of L. major in Tunisia that might improve
      our understanding of the parasite flow between geographically and temporally
      distinct populations. 

PMID- 26302441
TI  - Long-acting injectable vs oral risperidone for schizophrenia and co-occurring
      alcohol use disorder: a randomized trial.
AB  - OBJECTIVE: Alcohol use disorders worsen the course of schizophrenia. Although the
      atypical antipsychotic clozapine appears to decrease alcohol use in
      schizophrenia, risperidone does not. We have proposed that risperidone's
      relatively potent dopamine D2 receptor blockade may partly underlie its lack of
      effect on alcohol use. Since long-acting injectable (LAI) risperidone both
      results in lower average steady-state plasma concentrations than oral risperidone
      (with lower D2 receptor occupancy) and encourages adherence, it may be more
      likely to decrease heavy alcohol use (days per week of drinking 5 or more drinks
      per day) than oral risperidone. METHOD: Ninety-five patients with DSM-IV-TR
      diagnoses of schizophrenia and alcohol use disorder were randomized to 6 months
      of oral or LAI risperidone between 2005 and 2008. Explanatory (efficacy) analyses
      were carried out to evaluate the potential benefits of LAI under suitably
      controlled conditions (in contrast to real-world settings), with intent-to-treat
      analyses being secondary. RESULTS: Explanatory analyses showed that heavy
      drinking in the oral group worsened over time (P = .024) and that there was a
      statistical trend toward significance in the difference between the changes in
      heavy drinking days in the oral and LAI groups (P = .054). Furthermore, the 2
      groups differed in the mean number of drinking days per week (P = .035). The
      intent-to-treat analyses showed no difference in heavy drinking but did show a
      difference in average drinking days per week similar to that obtained from the
      explanatory analyses (P = .018). Neither explanatory nor intent-to-treat analyses
      showed any between-group differences in alcohol use as measured by intensity or
      the Alcohol Use Scale. The plasma concentrations of the active metabolite 9
      hydroxyrisperidone were significantly lower in patients taking LAI (P < .05),
      despite their significantly (overall) better treatment adherence (P < .005).
      CONCLUSION: For the population considered here, schizophrenia patients with
      alcohol use disorder appear to continue drinking some alcohol while taking either
      form of risperidone. Nonetheless, our data suggest that injectable risperidone
      may be a better choice than the oral form for these dual diagnosis patients.
      TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00130923.

PMID- 26302442
TI  - Dietary Milk Sphingomyelin Prevents Disruption of Skin Barrier Function in
      Hairless Mice after UV-B Irradiation.
AB  - Exposure to ultraviolet-B (UV-B) irradiation causes skin barrier defects. Based
      on earlier findings that milk phospholipids containing high amounts of
      sphingomyelin (SM) improved the water content of the stratum corneum (SC) in
      normal mice, here we investigated the effects of dietary milk SM on skin barrier
      defects induced by a single dose of UV-B irradiation in hairless mice. Nine week
      old hairless mice were orally administrated SM (146 mg/kg BW/day) for a total of
      ten days. After seven days of SM administration, the dorsal skin was exposed to a
      single dose of UV-B (20 mJ/cm2). Administration of SM significantly suppressed an
      increase in transepidermal water loss and a decrease in SC water content induced
      by UV-B irradiation. SM supplementation significantly maintained covalently-bound
      omega-hydroxy ceramide levels and down-regulated mRNA levels of acute
      inflammation-associated genes, including thymic stromal lymphopoietin,
      interleukin-1 beta, and interleukin-6. Furthermore, significantly higher levels
      of loricrin and transglutaminase-3 mRNA were observed in the SM group. Our study
      shows for the first time that dietary SM modulates epidermal structures, and can
      help prevent disruption of skin barrier function after UV-B irradiation. 

PMID- 26302443
TI  - Clarification technologies for monoclonal antibody manufacturing processes:
      Current state and future perspectives.
AB  - Considerable progress has been made increasing productivity of cell cultures to
      meet the rapidly growing demand for antibody biopharmaceuticals through increased
      cell densities and longer culture times. This in turn has dramatically increased
      the burden of process and product related impurities on the purification
      processes. In addition, current trends in the biopharmaceutical industry point
      toward both increased productivity and targeting smaller patient populations for
      new indications. Taken together, these developments are driving the industry to
      explore alternative separation technologies as a future manufacturing strategy.
      Clarification technologies well established in other industries, such as
      flocculation and precipitation are increasingly considered as a viable solution
      to address this bottleneck in antibody processes. However, several technical
      issues need to be fully addressed including suitability as a platform
      application, robustness, process cost, toxicity, and clearance. This review will
      focus on recent efforts to incorporate new generation clarification technologies
      for mammalian cell cultures producing monoclonal antibodies as well as challenges
      to their implementation supported by a case study.

PMID- 26302444
TI  - Tree Productivity Enhanced with Conversion from Forest to Urban Land Covers.
AB  - Urban areas are expanding, changing the structure and productivity of landscapes.
      While some urban areas have been shown to hold substantial biomass, the
      productivity of these systems is largely unknown. We assessed how conversion from
      forest to urban land uses affected both biomass structure and productivity across
      eastern Massachusetts. We found that urban land uses held less than half the
      biomass of adjacent forest expanses with a plot level mean biomass density of
      33.5 +/- 8.0 Mg C ha(-1). As the intensity of urban development increased, the
      canopy cover, stem density, and biomass decreased. Analysis of Quercus rubra tree
      cores showed that tree-level basal area increment nearly doubled following
      development, increasing from 17.1 +/- 3.0 to 35.8 +/- 4.7 cm(2) yr(-1). Scaling
      the observed stem densities and growth rates within developed areas suggests an
      aboveground biomass growth rate of 1.8 +/- 0.4 Mg C ha(-1) yr(-1), a growth rate
      comparable to nearby, intact forests. The contrasting high growth rates and lower
      biomass pools within urban areas suggest a highly dynamic ecosystem with rapid
      turnover. As global urban extent continues to grow, cities consider climate
      mitigation options, and as the verification of net greenhouse gas emissions
      emerges as critical for policy, quantifying the role of urban vegetation in
      regional-to-global carbon budgets will become ever more important.

PMID- 26302446
TI  - Bolus versus continuous infusion of microbubble contrast agent for liver
      ultrasound by using an automatic power injector in humans: A pilot study.
AB  - PURPOSE: To evaluate the feasibility of using continuous infusion, in comparison
      with bolus injection, of a sulfur hexafluoride-microbubble contrast agent to
      prolong the duration of hepatic parenchymal enhancement in humans during
      sonographic examination. METHODS: This pilot study was approved by our
      institution's ethics committee. Ten patients (5 men and 5 women; mean age +/- SD,
      65 +/- 10 years) each received two injections: a bolus injection (2 ml/s) and
      then continuous infusion (0.5 ml/min) of the contrast agent by using an automatic
      injector. Acquired cine clips were transferred to a personal computer, and the
      video intensity was quantified by dedicated software. RESULTS: From the time of
      the first microbubble visualization in the scanning plane, maximal enhancement
      was reached in 6.3 +/- 0.94 seconds after bolus injection and in 13.9 +/- 1.44
      seconds during continuous infusion (p = 0.002, Wilcoxon's test for paired data).
      Compared with bolus injection, continuous infusion prolonged the duration of
      contrast enhancement (4.3 minutes +/- 42 seconds versus 7.3 minutes +/- 40
      seconds; p = 0.002), although no statistically significant difference in maximal
      enhancement was observed (45 +/- 18% for bolus injection and 39 +/- 6% for
      continuous infusion; p = 0.62). CONCLUSIONS: Continuous infusion of sulfur
      hexafluoride-filled microbubbles via an automatic power injector prolongs hepatic
      contrast enhancement without significantly modifying the maximal enhancement over
      that at baseline. These data, coming from a pilot study, can be used to design a
      larger study with adequate statistical power.

PMID- 26302445
TI  - Blindness and Glaucoma: A Multicenter Data Review from 7 Academic Eye Clinics.
AB  - PURPOSE: To evaluate frequency, conversion rate, and risk factors for blindness
      in glaucoma patients treated in European Universities. METHODS: This multicenter
      retrospective study included 2402 consecutive patients with glaucoma in at least
      one eye. Medical charts were inspected and patients were divided into those blind
      and the remainder ('controls'). Blindness was defined as visual acuity<=0.05
      and/or visual field loss to less than 10 degrees . RESULTS: Unilateral and
      bilateral blindness were respectively 11.0% and 1.6% at the beginning, and 15.5%
      and 3.6% at the end of the observation period (7.5+/-5.5 years, range:1-25
      years); conversion to blindness (at least unilateral) was 1.1%/year. 134 eyes (97
      patients) developed blindness by POAG during the study. At the first access to
      study centre, they had mean deviation (MD) of -17.1+/-8.3 dB and treated
      intraocular pressure (IOP) of 17.1+/-6.6 mmHg. During follow-up the IOP decreased
      by 14% in these eyes but MD deteriorated by 1.1+/-3.5 dB/year, which was 5-fold
      higher than controls (0.2+/-1.6 dB/year). In a multivariate model, the best
      predictors for blindness by glaucoma were initial MD (p<0.001), initial IOP
      (p<0.001), older age at the beginning of follow-up (p<0.001), whereas final IOP
      was found to be protective (p<0.05). CONCLUSIONS: In this series of patients,
      blindness occurred in about 20%. Blindness by glaucoma had 2 characteristics:
      late diagnosis and/or late referral, and progression of the disease despite in
      most cases IOP was within the range of normality and target IOP was achieved; it
      could be predicted by high initial MD, high initial IOP, and old age.

PMID- 26302448
TI  - Solution structure and base specificity of cytotoxic RC-RNase 2 from Rana
      catesbeiana.
AB  - Cytotoxic ribonucleases found in the oocytes and early embryos of frogs with
      antitumor activity are well-documented. RC-RNase 2, a cytotoxic ribonuclease
      isolated from oocytes of bullfrog Rana catesbeiana, consists of 105 residues
      linked with 4 disulfide bridges and belongs to the bovine pancreatic ribonuclease
      (RNase A) superfamily. Among the RC-RNases, the base preference for RNase 2 is
      UpG but CpG for RC-RNase 4; while RC-RNase possesses the base specificity of both
      UpG and CpG. Interestingly, RC-RNase 2 or 4 has much lower catalytic activity but
      only three-fold less cytotoxicity than RC-RNase. Here, we report the NMR solution
      structure of rRC-RNase 2, comprising three alpha-helices and two sets of
      antiparallel beta-sheets. The differences of side-chain conformations of subsite
      residues among RNase A, RC-RNase, RC-RNase 4 and rRNase 2 are related to their
      distinct catalytic activities and base preferences. Furthermore, the substrate
      related residues in the base specificity among native RC-RNases are derived using
      the chemical shift perturbation on ligand binding. 

PMID- 26302449
TI  - Metformin ameliorates lipotoxicity-induced mesangial cell apoptosis partly via
      upregulation of glucagon like peptide-1 receptor (GLP-1R).
AB  - Glucagon like peptide-1 receptor (GLP-1R), known to be expressed in pancreatic
      beta cells, is also expressed in glomerular mesangial cells and its agonist has
      protective effects in diabetic nephropathy. However, its regulatory mechanisms by
      lipotoxicity in glomerular mesangial cells are not understood. We found that
      palmitate-mediated lipotoxicity increased apoptosis and decreased GLP-1R
      expression in a rat mesangial cell line. Silencing GLP-1R expression also
      increased mesangial cell apoptosis. Interestingly, metformin, one of the
      biguanide drugs that has anti-diabetic effects, attenuated lipotoxicity-induced
      mesangial cell apoptosis and restored GLP-1R expression. Moreover, this treatment
      alleviated GLP-1R knockdown-induced mesangial cell apoptosis. To further evaluate
      in vivo, diabetic obese db/db mice were administered metformin. Glomerular GLP-1R
      expression was diminished in db/db mice, as compared with db/m control mice.
      However, this decrease significantly recovered on metformin administration.
      Together, these data provide novel evidence that lipotoxicity decreases the
      mesangial GLP-1R expression in intact cells and in vivo. The decrease induced
      mesangial cell apoptosis. Furthermore, we provided the evidence that metformin
      treatment has a renal protective effect partly via increased mesangial GLP-1R
      expression. Our data suggested that regulation of GLP-1R expression could be a
      promising approach to treat diabetic nephropathy and the novel mechanism of
      metformin mediated GLP-1R regulation. 

PMID- 26302450
TI  - Assessing Long-Term Trend of Particulate Matter Pollution in the Pearl River
      Delta Region Using Satellite Remote Sensing.
AB  - Serious particulate matter (PM) pollution problems in many polluted regions of
      China have been frequently reported in recent years. Long-term exposure to
      ambient PM pollution is significantly associated with adverse health effects.
      Characterizing the long-term trends and variation in PM pollution is a basic
      requirement for evaluating long-term exposure and for guiding future policies to
      reduce the effects of air pollution on health. However, long-term, ground-based
      PM measurements are only available at a few fixed stations. In this study, an
      algorithm is developed and validated to estimate PM concentrations based on the
      satellite atmospheric optical depth with 1 km spatial resolution. The long-term
      trends of PM10 concentrations in the entire Pearl River Delta (PRD) region and
      different cities are quantified and discussed. From 2001 to 2013, the PM10
      pollution of the entire PRD region was dominated by a decreasing trend of -0.15
      +/- 0.23 MUg/m(3).yr. This decreasing PM10 trend was apparent over 75% of the PRD
      area, with the most significant decreases observed in the center of the region.
      However, the remaining 25%, mostly located in the outskirts of the region, showed
      an increasing PM10 trend. This overall decreasing trend indicates the
      effectiveness of the control measures applied in the past decade for the primary
      pollutants.

PMID- 26302451
TI  - High-resolution mapping of neuronal activation with balanced SSFP at 9.4 tesla.
AB  - PURPOSE: This work investigates the feasibility of high-resolution functional
      imaging of the human brain using passband balanced steady state free precession
      (SSFP) at 9.4 Tesla (T). To this end, the temporal signal stability, blood-oxygen
      level-dependent (BOLD)-related signal changes and sensitivity to frequency
      offsets were evaluated. METHODS: Three-dimensional slab selective and
      nonselective balanced SSFP have been implemented with minimized repetition time
      and high temporal resolution using parallel imaging, partial Fourier acquisition
      and elliptical scanning. Using a volume repetition time of approximately 3 s, a
      visual checker board stimulation was applied for 6 min. Temporal signal stability
      of balanced SSFP and BOLD response-related signal changes and sensitivity to
      frequency changes were evaluated. RESULTS: Activation could be detected in all
      volunteers with BOLD-related signal changes from 3% to 6%. At 1 mm isotropic
      resolution, the thermal noise SNR0 was 67 and the total temporal noise variation
      tSNR was 45 supporting a very high signal stability of balanced SSFP. No
      significant changes of activation at different offresonance frequencies were
      detected. CONCLUSION: High spatial and temporal resolution balanced SSFP at 9.4T
      to detect functional activation is feasible. Activation patterns and signal
      changes are stable and reproducible across subjects within the visual cortex, and
      comparable to reported values of SE-EPI at 7T and 9.4T. Magn Reson Med 76:163
      171, 2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 26302452
TI  - Synthesis and Investigation of the Effect of Substitution on the Structure,
      Physical Properties, and Electrochemical Properties of Anthracenodifuran
      Derivatives.
AB  - A series of syn/anti mixtures of anthradifuran (ADF) and substituent compounds
      were systematically synthesized, and the effect of substitution at the 5,11
      positions on the neutral and radical states of ADF was investigated. All
      compounds were measured and analyzed by absorption and fluorescence spectroscopy,
      cyclic voltammetry, electrochemical absorption spectroscopy, and DFT
      calculations. The absorption spectra of 5,11-substituent compounds in their
      neutral state were red-shifted. In addition, the substituted compounds exhibited
      increased thermal stability with respect to the parent 1a because of elongation
      of the pi-conjugation and an increased steric hindrance effect due to the bulky
      ethynyl substituent groups. The cyclic voltammograms of all of the compounds
      exhibited irreversible reduction potentials and irreversible oxidation
      potentials, except in the case of (trimethylsilyl)silylethynyl-substituted ADF.
      When the materials were subjected to oxidation/reduction potentials, the radical
      cation and anion species were generated. The absorption spectra of the radical
      cation species of the compounds exhibited similar characteristics and similar
      absorption ranges (550-1400 nm), whereas the spectra of the radical anion species
      were blue-shifted (550-850 nm) compared than that of the parent 1a(*-) (550-1100
      nm). The DFT computation results suggested that the radical states of lowest
      energy transitions occurred primarily from pi to pi(SOMO) or from pi(SOMO) to
      pi*.

PMID- 26302453
TI  - Just-in-Time to Save Lives: A Pilot Study of Layperson Tourniquet Application.
AB  - OBJECTIVES: The objective was to determine whether just-in-time (JiT)
      instructions increase successful tourniquet application by laypersons. METHODS:
      This was a randomized pilot study conducted in August 2014. The study occurred at
      the Uniformed Services University campus in Bethesda, Maryland. A total of 194
      volunteers without prior military service or medical training completed the
      study. The participant stood in front of a waist-down mannequin that had an
      exposed leg. An observer read a scenario card aloud that described a mass
      casualty event. The observer then asked the participant to apply a Combat
      Application Tourniquet (C-A-T) to the mannequin. Test participants received a 4 *
      6-inch card, with JiT instructions, in addition to their C-A-T; controls received
      no instructions. Participants were randomized in a 3:1 ratio of instructions to
      no instructions. The study's primary outcome was the proportion of successfully
      applied tourniquets by participants receiving JiT instructions compared to
      participants not receiving instructions. Secondary outcomes included the time for
      successful tourniquet placement, reasons for failed tourniquet application, and
      participants' self-reported willingness and comfort using tourniquets in real
      life settings. RESULTS: Just-in-time instructions more than doubled successful
      tourniquet placement. Participants supplied with JiT instructions placed a
      tourniquet successfully 44.14% of the time, compared to 20.41% of the time for
      controls without instructions (risk ratio = 2.16; 95% confidence interval = 1.21
      to 3.87; p = 0.003). CONCLUSIONS: Just-in-time instructions increase laypeople's
      successful application of C-A-T. This pilot study provides evidence that JiT
      instructions may assist the lay public in providing effective point-of-injury
      hemorrhage control.

PMID- 26302454
TI  - Epidural Corticosteroid Injections for Radiculopathy and Spinal Stenosis: A
      Systematic Review and Meta-analysis.
AB  - BACKGROUND: Use of epidural corticosteroid injections is increasing. PURPOSE: To
      review evidence on the benefits and harms of epidural corticosteroid injections
      in adults with radicular low back pain or spinal stenosis of any duration. DATA
      SOURCES: Ovid MEDLINE (through May 2015), Cochrane Central Register of Controlled
      Trials, Cochrane Database of Systematic Reviews, prior systematic reviews, and
      reference lists. STUDY SELECTION: Randomized trials of epidural corticosteroid
      injections versus placebo interventions, or that compared epidural injection
      techniques, corticosteroids, or doses. DATA EXTRACTION: Dual extraction and
      quality assessment of individual studies, which were used to determine the
      overall strength of evidence (SOE). DATA SYNTHESIS: 30 placebo-controlled trials
      evaluated epidural corticosteroid injections for radiculopathy, and 8 trials were
      done for spinal stenosis. For radiculopathy, epidural corticosteroids were
      associated with greater immediate-term reduction in pain (weighted mean
      difference on a scale of 0 to 100, -7.55 [95% CI, -11.4 to -3.74]; SOE,
      moderate), function (standardized mean difference after exclusion of an outlier
      trial, -0.33 [CI, -0.56 to -0.09]; SOE, low), and short-term surgery risk
      (relative risk, 0.62 [CI, 0.41 to 0.92]; SOE, low). Effects were below predefined
      minimum clinically important difference thresholds, and there were no longer-term
      benefits. Limited evidence showed no clear effects of technical factors, patient
      characteristics, or comparator interventions on estimates. There were no clear
      effects of epidural corticosteroid injections for spinal stenosis (SOE, low to
      moderate). Serious harms were rare, but harms reporting was suboptimal (SOE,
      low). LIMITATIONS: The review was restricted to English-language studies. Some
      meta-analyses were based on small numbers of trials (particularly for spinal
      stenosis), and most trials had methodological shortcomings. CONCLUSION: Epidural
      corticosteroid injections for radiculopathy were associated with immediate
      reductions in pain and function. However, benefits were small and not sustained,
      and there was no effect on long-term surgery risk. Limited evidence suggested no
      effectiveness for spinal stenosis.

PMID- 26302447
TI  - Consent for Brain Tissue Donation after Intracerebral Haemorrhage: A Community
      Based Study.
AB  - BACKGROUND: Spontaneous intracerebral haemorrhage is a devastating form of stroke
      and its incidence increases with age. Obtaining brain tissue following
      intracerebral haemorrhage helps to understand its cause. Given declining autopsy
      rates worldwide, the feasibility of establishing an autopsy-based collection and
      its generalisability are uncertain. METHODS: We used multiple overlapping sources
      of case ascertainment to identify every adult diagnosed with intracerebral
      haemorrhage between 1st June 2010-31st May 2012, whilst resident in the Lothian
      region of Scotland. We sought consent from patients with intracerebral
      haemorrhage (or their nearest relative if the patient lacked mental capacity) to
      conduct a research autopsy. RESULTS: Of 295 adults with acute intracerebral
      haemorrhage, 110 (37%) could not be approached to consider donation. Of 185
      adults/relatives approached, 91 (49%) consented to research autopsy. There were
      no differences in baseline demographic variables or markers of intracerebral
      haemorrhage severity between consenters and non-consenters. Adults who died and
      became donors (n = 46) differed from the rest of the cohort (n = 249) by being
      older (median age 80, IQR 76-86 vs. 75, IQR 65-83, p = 0.002) and having larger
      haemorrhages (median volume 23 ml, IQR 13-50 vs. 13 ml, IQR 4-40; p = 0.002).
      CONCLUSIONS: Nearly half of those approached consent to brain tissue donation
      after acute intracerebral haemorrhage. The characteristics of adults who gave
      consent were comparable to those in an entire community, although those who
      donate early are older and have larger haemorrhage volumes.

PMID- 26302456
TI  - Involvement of lncRNA dysregulation in gastric cancer.
AB  - Benefiting from the fast development of sequencing technique and bioinformatics
      methods, more and more new long non-coding RNAs (lncRNAs) are discovered and
      identified. lncRNAs were firstly thought to be transcription noise that from
      genome desert without biological function; however, as the discovery of lncRNA
      XIST and HOTAIR uncovers the emerging roles of lncRNAs in development and
      tumorigenesis. In the past decades, accumulating evidence have indicated that
      lncRNAs involve in a wide range of biological functions, such as X-chromosome
      inactivation, reprogramming stem cell pluripotency, regulation of the immune
      response and carcinogenesis. Although lots of studies have demonstrated that
      dysregulation of lncRNAs involve in diverse diseases including cancers, the
      underlying molecular mechanisms of lncRNAs are not well documented.
      Interestingly, our previous studies and others' have shown that numerous of
      lncRNAs expression was misregulated in gastric cancer. In this review, we will
      focus on the dysregulated lncRNAs and their biological function and underlying
      pathways or mechanisms in GC. Finally, we will discuss the potential roles of
      lncRNAs acting as biomarkers or therapeutic targets in GC patients. 

PMID- 26302455
TI  - Boundary Associated Long Noncoding RNA Mediates Long-Range Chromosomal
      Interactions.
AB  - CCCTC binding factor (CTCF) is involved in organizing chromosomes into mega base
      sized, topologically associated domains (TADs) along with other factors that
      define sub-TAD organization. CTCF-Cohesin interactions have been shown to be
      critical for transcription insulation activity as it stabilizes long-range
      interactions to promote proper gene expression. Previous studies suggest that
      heterochromatin boundary activity of CTCF may be independent of Cohesin, and
      there may be additional mechanisms for defining topological domains. Here, we
      show that a boundary site we previously identified known as CTCF binding site 5
      (CBS5) from the homeotic gene cluster A (HOXA) locus exhibits robust promoter
      activity. This promoter activity from the CBS5 boundary element generates a long
      noncoding RNA that we designate as boundary associated long noncoding RNA-1
      (blncRNA1). Functional characterization of this RNA suggests that the transcript
      stabilizes long-range interactions at the HOXA locus and promotes proper
      expression of HOXA genes. Additionally, our functional analysis also shows that
      this RNA is not needed in the stabilization of CTCF-Cohesin interactions however
      CTCF-Cohesin interactions are critical in the transcription of blncRNA1. Thus,
      the CTCF-associated boundary element, CBS5, employs both Cohesin and noncoding
      RNA to establish and maintain topologically associated domains at the HOXA locus.

PMID- 26302457
TI  - Effective End Group Modification of Poly(3-hexylthiophene) with Functional
      Electron-Deficient Moieties for Performance Improvement in Polymer Solar Cell.
AB  - A series of end-functionalized poly(3-hexylthiophene)s (P3HTs) were synthesized
      by end-capping with electron-deficient moieties (EDMs, oxadiazole (OXD) and
      triazole (TAZ)) to prevent the negative influence of bromine chain ends in the
      common uncapped P3HT in polymer solar cell (PSC) applications. On the basis of
      the electron-withdrawing capability of the planar OXD end groups, P3HT-end-OXD
      relative to the uncapped P3HT exhibits a raised absorption coefficient, extended
      exciton lifetime, and increased crystalline order in the blend with PCBM, leading
      to an effectual improvement in photovoltaic parameters. However, P3HT-end-TAZ has
      an opposite result even worse than that of the uncapped P3HT, arising from bulky
      TAZ end groups. As a consequence, P3HT-end-OXD gives a power conversion
      efficiency (PCE) of 4.24%, which is higher than those of the uncapped P3HT
      (3.28%) and P3HT-end-TAZ (0.50%). The result demonstrates that the EDM
      modification is a valuable method to tailor the structural defect of polymer
      chain ends. However, the efficacy is dependent on the structure of EDM. 

PMID- 26302458
TI  - Indoor dermatitis due to Aeroglyphus robustus.

PMID- 26302459
TI  - Controlled Suppression of Wear on the Nanoscale by Ultrasonic Vibrations.
AB  - Wear on the nanoscale, as evidenced by the formation of periodic ripples on a
      model polystyrene thin film while a sharp tip is sliding on it with a normal
      force in the MUN range, is shown to be suppressed by the application of
      ultrasonic vibrations of amplitude Aexc. An accurate calibration of the
      transducer excitation amplitude is achieved by a home-built setup based on a
      laser Doppler vibrometer. The corrugation of the typical ripple pattern that is
      formed in the absence of vibrations is reduced when the excitation frequency
      matches the contact resonance of the system and Aexc progressively increases.
      Above a critical value of Aexc, the ripples completely disappear, while the
      friction levels off at a finite value determined by the normal force and the
      vibration amplitude. This value can be significantly smaller than the value of
      the macroscopic friction coefficient. In addition to the control of wear in
      general, this opens up the possibility of controlled nanolithography with
      improved accuracy. 

PMID- 26302460
TI  - Accuracy of 18F-FDG PET-CT in triaging lung cancer patients with suspected brain
      metastases for MRI.
AB  - OBJECTIVE: Brain metastases are common in lung cancer. Whole-body 2-deoxy-2
      [fluorine-18]fluoro-D-glucose ([F]FDG) PET/computed tomography (CT) is used for
      general staging, but MRI is the best modality for characterizing brain
      abnormalities. We aimed to determine whether PET/CT is suitable for selecting
      patients for MRI on the suspicion of brain metastases. MATERIALS AND METHODS: F
      FDG PET/CT (from the vertex to mid-thigh) was performed in 1108 consecutive
      patients suspected of lung cancer. The final diagnoses were extracted from
      medical records as lung cancer, with or without brain metastases, other kinds of
      cancers, or no cancer. The sensitivity, specificity, and positive predictive
      value for detecting brain metastases were calculated. Interobserver variation was
      tested in a subset of 88 PET/CT scans. RESULTS: Of the 1108 referred patients,
      596 had lung cancer. Sixty-six had brain metastases. One PET/CT was false
      positive. Thirty-one scans were true positive among the 43 patients who were
      diagnosed with brain metastases 1 month before to 3 months after PET/CT
      (metastasis prevalence, 7.3%). Twelve PET/CT scans were false negative.
      Sensitivity, specificity, and positive predictive values were 72, 100, and 97%,
      respectively. Interobserver agreement between two experienced observers was high
      (kappa=0.83), whereas agreement between the experienced and the inexperienced
      observer was poor. CONCLUSION: The sensitivity of brain PET/CT for detecting
      brain metastases in lung cancer was above 70%, and the specificity was very high.
      Thus, PET/CT may be suitable for selecting patients for MRI in diagnostic centers
      that do not perform routine MRI in the pretherapeutic staging workup. The
      agreement among experienced readers was very high.

PMID- 26302461
TI  - Reducing CT dose in myocardial perfusion SPECT/CT.
AB  - The aim of this study was to reduce the radiation dose arising from computed
      tomography (CT) attenuation correction to single photon emission computed
      tomography myocardial perfusion imaging studies without adversely affecting its
      accuracy. Using the Perspex CTDI phantom with the Xi detector to measure dose, CT
      scans were acquired using the Siemens Symbia T over the full range of CT settings
      available. Using the default setting 'AECmean', the measured dose at the centre
      of the phantom was 1.68 mGy and the breast dose from the scout view was 0.30 mGy.
      The lowest dose was achieved using the dose modulation setting in which the doses
      were reduced to 1.21 mGy and undetectable (<0.01 mGy), respectively. To observe
      the effect of changing these settings, 30 patients received a stress scan with
      default CT settings and a rest scan utilizing single photon emission computed
      tomography-guided CT and the dose modulation CT settings. Results showed a mean
      effective dose reduction of 23.6%. The dose reduction was greatest for larger
      patients, with the largest dose reduction for one patient being 72%. There was no
      apparent difference in attenuation correction between the two sets of resultant
      images. These new lower-dose settings are now applied to all clinical myocardial
      perfusion imaging studies. 

PMID- 26302462
TI  - Thyroid remnant ablation in differentiated thyroid cancer: searching for the most
      effective radioiodine activity and stimulation strategy in a real-life scenario.
AB  - OBJECTIVE: Differentiated thyroid cancer is rare, but the incidence has been
      increasing in the last few decades. Early treatment is based on surgery and
      thyroid remnant ablation (TRA) by means of radioiodine therapy. Despite
      radioiodine being widely used for decades, the choice of ablative activity is
      generally empirical and no consensus has been reached to date. The aim of our
      study was to compare the efficacy and safety of different radioiodine activities.
      In addition, we compared the ablation rate in patients treated in the hypothyroid
      state or after recombinant human thyroid-stimulating hormone (rhTSH)
      administration, retrospectively reviewing the records of 471 patients affected by
      differentiated thyroid cancer. PATIENTS AND METHODS: Patients were subdivided
      into three groups on the basis of the different activities of radioiodine
      administered and taking into account the different approaches used to perform the
      therapy: thyroid hormonal withdrawal or rhTSH stimulation. RESULTS: The success
      of TRA was evaluated 12 months later. TRA was obtained in 62/79 (78.5%) in group
      A (1110 MBq in the hypothyroid state), 183/190 (96.3%) in group B [2220 MBq in
      the hypothyroid state or after rhTSH administration: 87/90 (97%) and 96/100 (96%)
      patients, respectively], 199/202 (98.5%) in group C [3700 MBq in hypothyroid
      state or after rhTSH administration: 98/100 (98%) and 101/102 (99%) patients,
      respectively]. CONCLUSION: Our data demonstrate that 2220 and 3700 MBq
      radioiodine are more effective compared with 1110 MBq in TRA, without significant
      differences between 2220 and 3700 MBq or between hypothyroidism and euthyroidism.
      We suggest rhTSH-aided TRA with 2220 MBq iodine-131, as this approach permits
      efficacious treatment, thereby reducing side effects, absorbed dose to body and
      hospital stay.

PMID- 26302463
TI  - The relative value of 18F-FDG PET interpretation criteria in generating a
      probabilistic approach for characterization of pulmonary nodules.
AB  - PURPOSE: The evaluation of pulmonary nodules constitutes a large part of PET-CT
      studies. In this study, we aimed to evaluate the different interpretation
      criteria in F-fluorodeoxyglucose PET attenuation-corrected and non-attenuation
      corrected studies as individual predictors of malignancy in order to propose a
      useful combination of criteria that can be used in daily practice to classify
      nodules appropriately. PATIENTS AND METHODS: We performed a historical
      prospective survey of all consecutive patients referred to our service for the
      initial assessment of pulmonary nodules and sought the final characterization of
      these nodules either from tissue sampling or from radiological and clinical
      follow-up. RESULTS: A total of 104 nodules from 82 patients were included, with a
      prevalence of malignancy of 53%. Absence of uptake on non-attenuation-corrected
      studies was found to be the best predictive criterion for benignancy, with a
      negative predictive value of 97%, and the highest relative risk for malignancy,
      with a value of 20.9. Uptake higher than that of the mediastinum on attenuation
      corrected images was found to be the best criterion for predicting malignancy,
      with a positive predictive value of 89% and a sensitivity of 73%, which is
      slightly better than the use of a maximal standardized uptake value cutoff of
      3.0. By combining our best negative and positive criteria, we were able to
      classify 71% (74/104) of the lung nodules with a high level of confidence. More
      specifically, these two criteria allowed the correct classification of 72%
      (40/55) of malignant nodules and 57% (28/49) of benign nodules. The 30 remaining
      nodules were equally distributed in terms of malignancy and had similar
      characteristics on both PET and CT images. CONCLUSION: A probabilistic approach
      to pulmonary nodule characterization may help the reading physician to
      appropriately classify lung nodules into useful categories for the treating
      physician, moving away from nonstandardized reporting terms.

PMID- 26302464
TI  - Electrostatic Force Microscopic Characterization of Early Stage Carbon Deposition
      on Nickel Anodes in Solid Oxide Fuel Cells.
AB  - Carbon deposition on nickel anodes degrades the performance of solid oxide fuel
      cells that utilize hydrocarbon fuels. Nickel anodes with BaO nanoclusters
      deposited on the surface exhibit improved performance by delaying carbon
      deposition (i.e., coking). The goal of this research was to visualize early stage
      deposition of carbon on nickel surface and to identify the role BaO nanoclusters
      play in coking resistance. Electrostatic force microscopy was employed to
      spatially map carbon deposition on nickel foils patterned with BaO nanoclusters.
      Image analysis reveals that upon propane exposure initial carbon deposition
      occurs on the Ni surface at a distance from the BaO features. With continued
      exposure, carbon deposits penetrate into the BaO-modified regions. After extended
      exposure, carbon accumulates on and covers BaO. The morphology and spatial
      distribution of deposited carbon was found to be sensitive to experimental
      conditions. 

PMID- 26302466
TI  - Blindness in a wild American black bear cub (Ursus americanus).
AB  - An approximately six-month-old wild American black bear (Ursus americanus) was
      found wandering in Saskatchewan and was presented to the Veterinary Medical
      Centre of the Western College of Veterinary Medicine for apparent blindness.
      Clinical examination confirmed an inability to navigate a photopic maze,
      bilateral tapetal hyper-reflectivity, fundi devoid of retinal vessels, and small
      pale optic nerve papillae. Single-flash electroretinography revealed A and B-wave
      amplitudes of approximately 40 and 140 microvolts, respectively, in both eyes.
      Histologic abnormalities included bilateral optic papillary mineralization and
      bilateral segmental optic nerve degeneration, with occasional intralesional
      lymphocytes confirmed with immunohistochemistry for CD3+. There was also
      bilateral multifocal retinal dysplasia, gliosis, lymphocytic retinitis, a
      complete lack of retinal blood vessels, an intravitreal vascular membrane, and a
      mild lymphocytic-plasmacytic uveitis with small pre-iridal cellular membranes.
      The presence of a positive ERG in a blind bear with numerous retinal ganglion
      cells and degenerative changes in the optic nerve are most consistent with vision
      loss due to optic nerve injury, which given the young age of the bear likely
      occurred during ocular development. The presence of ocular inflammation suggests
      this injury resulted from an inflammatory/infectious process. The etiology could
      not be determined. Hepatic concentrations of vitamin A were within the normal
      reference range for domestic species. Pan-herpesvirus PCR and
      immunohistochemistry for canine distemper virus and Toxoplasma gondii were
      negative, although this does not rule out these or other infectious etiologies.
      This represents the first case report of neonatal or congenital ocular
      abnormalities in an ursid species.

PMID- 26302465
TI  - Measurement of Thermal Effects of Doppler Ultrasound: An In Vitro Study.
AB  - OBJECTIVE: Ultrasound is considered a safe imaging modality and is routinely
      applied during early pregnancy. However, reservations are expressed concerning
      the application of Doppler ultrasound in early pregnancy due to energy emission
      of the ultrasound probe and its conversion to heat. The objective of this study
      was to evaluate the thermal effects of emitted Doppler ultrasound of different
      ultrasound machines and probes by means of temperature increase of in-vitro test
      media. METHODS: We investigated the energy-output of 5 vaginal and abdominal
      probes of 3 ultrasound machines (GE Healthcare, Siemens, Aloka). Two in-vitro
      test objects were developed at the Center for Medical Physics and Biomedical
      Engineering, Medical University Vienna (water bath and hydrogel bath).
      Temperature increase during Doppler ultrasound emission was measured via thermal
      sensors, which were placed inside the test objects or on the probes' surface.
      Each probe was emitting for 5 minutes into the absorbing test object with 3
      different TI/MI settings in Spectral Doppler mode. RESULTS: During water bath
      test, temperature increase varied between 0.1 and 1.0 degrees C, depending on
      probe, setting and focus, and was found highest for spectral Doppler mode alone.
      Maximum temperature increase was found during the surface heating test, where
      values up to 2.4 degrees C could be measured within 5 minutes of emission.
      CONCLUSIONS: Activation of Doppler ultrasound in the waterbath model causes a
      significant increase of temperature within one minute. Thermally induced effects
      on the embryo cannot be excluded when using Doppler ultrasound in early
      pregnancy.

PMID- 26302468
TI  - Errata.
AB  - [This corrects the article DOI: 10.11919/j.issn.1002-0829.214151.]. 

PMID- 26302467
TI  - Schmallenberg Virus in Belgium: Estimation of Impact in Cattle and Sheep Herds.
AB  - Schmallenberg virus (SBV) emerged during summer 2011. SBV induced an unspecific
      syndrome in cattle and congenital signs (abortions, stillbirths and
      malformations) in domestic ruminants. To study the impact of SBV in Belgium, a
      phone survey was conducted upon September 2012. Hereto two groups of cattle
      farmers (A and B) and two groups of sheep farmers (C and D) were randomly
      selected. Farms from groups A (n = 53) and C (n = 42) received SBV-positive
      result at RT-PCR in the Belgian National Reference Laboratory (NRL). Farms from
      groups B (n = 29) and D (n = 44) never sent suspected samples to NRL for SBV
      analysis but were however presumed seropositive for SBV after the survey.
      Questionnaires related to reproduction parameters and clinical signs observed in
      newborn and adult animals were designed and addressed to farmers. As calculated
      on a basis of farmers' observations, 4% of calves in group A and 0.5% in group B
      were reported aborted, stillborn or deformed due to SBV in 2011-2012. The impact
      as observed by sheep farmers was substantially higher with 19% of lambs in group
      C and 11% in group D that were reported aborted, stillborn or deformed due to SBV
      in 2011-2012. Interestingly, abortions or stillbirths were not clear consequences
      of SBV outbreak in cattle farms, and the birth of a deformed animal was an
      essential condition to suspect SBV presence in cattle and sheep farms. This study
      contributes to a better knowledge of the impact of the SBV epidemic. The results
      suggest that SBV impacted Belgian herds mostly by the birth of deformed calves,
      stillborn lambs and deformed lambs. This work also demonstrates that the birth of
      a deformed calf or lamb was a trigger for the farmer to suspect the presence of
      SBV and send samples to NRL for further analyses.

PMID- 26302469
TI  - Right hand, left brain: genetic and evolutionary bases of cerebral asymmetries
      for language and manual action.
AB  - Most people are right-handed and left-cerebrally dominant for language. This
      pattern of asymmetry, as well as departures from it, have been reasonably
      accommodated in terms of a postulated gene with two alleles, one disposing to
      this common pattern and the other leaving the direction of handedness and
      language asymmetry to chance. There are some leads as to the location of the gene
      or genes concerned, but no clear resolution; one possibility is that the chance
      factor is achieved by epigenetic cancelling of the lateralizing gene rather than
      through a chance allele. Neurological evidence suggests that the neural basis of
      manual praxis, including pantomime and tool use, is more closely associated with
      cerebral asymmetry for language than with handedness, and is homologous with the
      so-called "mirror system" in the primate brain, which is specialized for manual
      grasping. The evidence reviewed supports the theory that language itself evolved
      within the praxic system, and became lateralized in humans, and perhaps to a
      lesser extent in our common ancestry with the great apes. WIREs Cogn Sci 2012,
      3:1-17. doi: 10.1002/wcs.158 For further resources related to this article,
      please visit the WIREs website. 

PMID- 26302470
TI  - Physics for infants: characterizing the origins of knowledge about objects,
      substances, and number.
AB  - Adults possess a great deal of knowledge about how objects behave and interact in
      our every day environment, yet several puzzles remain unsolved regarding how we
      manage this ubiquitous skill. The notion of intuitive physics has been a central
      focus of research on cognitive development in infancy. This article focuses on
      the origins of knowledge about objects, substances, and number concepts in
      infancy. The article reviews common themes of solidity, continuity, cohesion, and
      property changes as they have been studied with regard to infants' knowledge
      about objects and more recently with regard to infants' knowledge about
      substances. In addition, we review how object and substance knowledge interfaces
      with number knowledge systems. The evidence supports the view that certain core
      principles about these domains are present as early as we can test for them and
      the nature of the underlying representation is best characterized as primitive
      initial concepts that are elaborated and refined through learning and experience.
      WIREs Cogn Sci 2012, 3:19-27. doi: 10.1002/wcs.157 For further resources related
      to this article, please visit the WIREs website. 

PMID- 26302471
TI  - Gustation.
AB  - Much has been discovered over the last few decades about the anatomy and
      physiology of the human taste system, most notably its receptor mechanisms and
      intermodal factors that influence its function. While the taste system works in
      concert with the olfactory, somatosensory, auditory, and visual sensory systems
      to establish the overall gestalt of flavor, its primary specialization is to
      ensure that the organism obtains energy, maintains proper electrolyte balance,
      and avoids ingestion of toxic substances. Despite its focus on inborn functions,
      taste-like its sister sense of smell-is remarkably malleable, reflecting the need
      to adapt to changing circumstances and general nutrient availability. It is now
      widely appreciated that taste dysfunction is common in many diseases and
      disorders, and is a frequent side effect of a number of medications. This
      interdisciplinary review examines salient aspects of the human gustatory system,
      including its anatomy, physiology, and pathophysiology. WIREs Cogn Sci 2012, 3:29
      46. doi: 10.1002/wcs.156 For further resources related to this article, please
      visit the WIREs website. 

PMID- 26302472
TI  - The amnesias.
AB  - Throughout history, memory and amnesia have been central to philosophical thought
      and empirical investigation. There has been particular interest in whether there
      are multiple forms of memory, how they are represented in the brain, how they are
      parsed following neurological compromise, and how their breakdown is best
      characterized. Differential abilities among amnestic individuals have advanced
      the distinction between various forms of memory, such as implicit and explicit
      memory in the case of H.M., and episodic and semantic memory in the case of K.C.
      This overview brings together a variety of perspectives on memory and the
      amnesias, from Clinical Neuropsychology, Neurology, and Cognitive Science, to
      Animal and Human Neuroscience. We begin with a brief history of the study of
      memory organization in the healthy brain and dissociations in memory as uncovered
      in extensively studied cases of amnesia. Memory impairment resulting from damage
      to the medial temporal lobe (MTL), diencephalon, basal forebrain, and the frontal
      lobes is then elaborated, with a focus on MTL amnesia, which has received the
      most attention among memory researchers. Alternative theories of MTL amnesia are
      considered through a selective review of the current amnesia and neuroimaging
      literatures on the seemingly disparate roles of the hippocampus in episodic and
      spatial memory, future imagining, perception, implicit memory, and working
      memory. If amnesia is a disorder that is not restricted to explicit (consciously
      accessible) memory, this will force us to rethink the way in which memory is
      represented in the human brain. WIREs Cogn Sci 2012, 3:47-63. doi:
      10.1002/wcs.155 For further resources related to this article, please visit the
      WIREs website. 

PMID- 26302473
TI  - Neural and BOLD responses across the brain.
AB  - Functional Magnetic Resonance Imaging (fMRI) has quickly grown into one of the
      most important tools for studying brain function, especially in humans. Despite
      its prevalence, we still do not have a clear picture of what exactly the blood
      oxygenation level dependent (BOLD) signal represents or how it compares to the
      signals obtained with other methods (e.g., electrophysiology). We particularly
      refer to single neuron recordings and electroencephalography when we mention
      'electrophysiological methods', given that these methods have been used for more
      than 50 years, and have formed the basis of much of our current understanding of
      brain function. Brain function involves the coordinated activity of many
      different areas and many different cell types that can participate in an enormous
      variety of processes (neural firing, inhibitory and excitatory synaptic activity,
      neuromodulation, oscillatory activity, etc.). Of these cells and processes, only
      a subset is sampled with electrophysiological techniques, and their contribution
      to the recorded signals is not exactly known. Functional imaging signals are
      driven by the metabolic needs of the active cells, and are most likely also
      biased toward certain cell types and certain neural processes, although we know
      even less about which processes actually drive the hemodynamic response. This
      article discusses the current status on the interpretation of the BOLD signal and
      how it relates to neural activity measured with electrophysiological techniques.
      WIREs Cogn Sci 2012, 3:75-86. doi: 10.1002/wcs.153 For further resources related
      to this article, please visit the WIREs website. 

PMID- 26302474
TI  - Binocular rivalry: competition and inhibition in visual perception.
AB  - When the brain is presented with ambiguous visual stimuli supporting two
      interpretations, perception becomes bistable and alternates over time between one
      interpretation and the other. This process contains elements of competition
      (between the rivaling percepts) as well as inhibition, as the percepts are
      mutually exclusive so that one is always suppressed. This review covers the most
      widely studied form of bistable perception-binocular rivalry. Suppression in
      rivalry is covered in detail, including discussion of its general and specific
      components, its local nature and spatial organization, techniques for quantifying
      it, and the role of global feedback. The competitive dynamics of rivalry are
      discussed within the context of the classical 'adapting reciprocal inhibition'
      model of rivalry and recent evidence supporting this model is discussed. This
      model is contrasted with alternative models based on late competition and with
      hybrid models. Finally, the role of attention in rivalry is examined and
      commonalities with other forms of bistable perception are noted. WIREs Cogn Sci
      2012, 3:87-103. doi: 10.1002/wcs.151 For further resources related to this
      article, please visit the WIREs website. 

PMID- 26302475
TI  - Folkbiology.
AB  - Recent work in cognitive science suggests that children have framework theories
      unique to specific domains such as physics, psychology, and biology that provide
      causal explanations and support predictions about phenomena within them. They
      further guide how children develop the later theories of adults, both formal and
      informal. In this article, we focus on a particular framework or naive theory,
      folkbiology, and review debates concerning how it ought best to be characterized,
      its origins and developmental course, whether aspects of it can be said to be
      universal to people in all cultural settings, how it informs our understanding of
      the brain, and what implications it has for science education. In so doing, we
      discuss how the cognitive scientific study of folkbiology takes us across
      disciplinary bounds into related work in the philosophy of science, cultural
      anthropology, neuropsychology, and education. WIREs Cogn Sci 2012, 3:105-115.
      doi: 10.1002/wcs.150 For further resources related to this article, please visit
      the WIREs website. 

PMID- 26302476
TI  - Rethinking visual scene perception.
AB  - A classic puzzle in understanding visual scene perception is how to reconcile the
      physiological constraints of vision with the phenomenology of seeing. Vision
      captures information via discrete eye fixations, interrupted by saccadic
      suppression, and limited by retinal inhomogeneity. Yet scenes are effortlessly
      perceived as coherent, continuous, and meaningful. Two conceptualizations of
      scene representation will be contrasted. The traditional visual-cognitive model
      casts visual scene representation as an imperfect reflection of the visual
      sensory input alone. By contrast, a new multisource model casts visual scene
      representation in terms of an egocentric spatial framework that is 'filled-in' by
      visual sensory input, but also by amodal perception, and by expectations and by
      constraints derived from rapid-scene classification and object-to-context
      associations. Together, these nonvisual sources serve to 'simulate' a likely
      surrounding scene that the visual input only partially reveals. Pros and cons of
      these alternative views will be discussed. WIREs Cogn Sci 2012, 3:117-127. doi:
      10.1002/wcs.149 For further resources related to this article, please visit the
      WIREs website. 

PMID- 26302478
TI  - Antibacterial monoclonal antibodies: the next generation?
AB  - There is a clear need for renewed efforts to combat the increasing incidence of
      antibiotic resistance. While the antibiotic resistance epidemic is due in part to
      the misuse of antibiotics, even proper empiric antibiotic therapy increases the
      selective pressure and potential for drug-resistance and spread of resistance
      mechanisms between bacteria. Antibiotic resistance coupled with the detrimental
      effects of broad-spectrum antibiotics on the healthy microbiome, have led the
      field to explore pathogen specific antibacterials such as monoclonal antibodies
      (mAbs). Medical need along with advances in mAb discovery, engineering, and
      production have driven significant effort developing mAb-based antibacterials. If
      successful, they will provide physicians with precision weapons to combat
      bacterial infections and can help prevent a return to a pre-antibiotic era. 

PMID- 26302479
TI  - Human calprotectin is an iron-sequestering host-defense protein.
AB  - Human calprotectin (CP) is a metal-chelating antimicrobial protein of the innate
      immune response. The current working model states that CP sequesters manganese
      and zinc from pathogens. We report the discovery that CP chelates iron and
      deprives bacteria of this essential nutrient. Elemental analysis of CP-treated
      growth medium establishes that CP reduces the concentrations of manganese, iron
      and zinc. Microbial growth studies reveal that iron depletion by CP contributes
      to the growth inhibition of bacterial pathogens. Biochemical investigations
      demonstrate that CP coordinates Fe(II) at an unusual hexahistidine motif, and the
      Mossbauer spectrum of (57)Fe(II)-bound CP is consistent with coordination of high
      spin Fe(II) at this site (delta = 1.20 mm/s, DeltaEQ = 1.78 mm/s). In the
      presence of Ca(II), CP turns on its iron-sequestering function and exhibits
      subpicomolar affinity for Fe(II). Our findings expand the biological coordination
      chemistry of iron and support a previously unappreciated role for CP in mammalian
      iron homeostasis. 

PMID- 26302481
TI  - A Riemannian geometry theory of human movement: The geodesic synergy hypothesis.
AB  - Mass-inertia loads on muscles change with posture and with changing mechanical
      interactions between the body and the environment. The nervous system must
      anticipate changing mass-inertia loads, especially during fast multi-joint
      coordinated movements. Riemannian geometry provides a mathematical framework for
      movement planning that takes these inertial interactions into account. To
      demonstrate this we introduce the controlled (vs. biomechanical) degrees of
      freedom of the body as the coordinate system for a configuration space with
      movements represented as trajectories. This space is not Euclidean. It is endowed
      at each point with a metric equal to the mass-inertia matrix of the body in that
      configuration. This warps the space to become Riemannian with curvature at each
      point determined by the differentials of the mass-inertia at that point. This
      curvature takes nonlinear mass-inertia interactions into account with lengths,
      velocities, accelerations and directions of movement trajectories all differing
      from those in Euclidean space. For newcomers to Riemannian geometry we develop
      the intuitive groundwork for a Riemannian field theory of human movement
      encompassing the entire body moving in gravity and in mechanical interaction with
      the environment. In particular we present a geodesic synergy hypothesis
      concerning planning of multi-joint coordinated movements to achieve goals with
      minimal muscular effort. 

PMID- 26302480
TI  - N-terminal domains mediate [2Fe-2S] cluster transfer from glutaredoxin-3 to
      anamorsin.
AB  - In eukaryotes, cytosolic monothiol glutaredoxins are proteins implicated in
      intracellular iron trafficking and sensing via their bound [2Fe-2S] clusters. We
      define a new role of human cytosolic monothiol glutaredoxin-3 (GRX3) in
      transferring its [2Fe-2S] clusters to human anamorsin, a physical and functional
      protein partner of GRX3 in the cytosol, whose [2Fe-2S] cluster-bound form is
      involved in the biogenesis of cytosolic and nuclear Fe-S proteins. Specific
      protein recognition between the N-terminal domains of the two proteins is the
      mandatory requisite to promote the [2Fe-2S] cluster transfer from GRX3 to
      anamorsin. 

PMID- 26302482
TI  - Suppressed expression of choline monooxygenase in sugar beet on the accumulation
      of glycine betaine.
AB  - Glycine betaine (GB) is an important osmoprotectant and synthesized by two-step
      oxidation of choline. Choline monooxygenase (CMO) catalyzes the first step of the
      pathway and is believed to be a rate limiting step for GB synthesis. Recent
      studies have shown the importance of choline-precursor supply for GB synthesis.
      In order to investigate the role of CMO for GB accumulation in sugar beet (Beta
      vulgaris), transgenic plants carrying the antisense BvCMO gene were developed.
      The antisense BvCMO plants showed the decreased activity of GB synthesis from
      choline compared to wild-type (WT) plants which is well related to the suppressed
      level of BvCMO protein. However, GB contents were similar between transgenic and
      WT plants with the exception of young leaves and storage roots. Transgenic plants
      showed enhanced susceptibility to salt stress than WT plants. These results
      suggest the importance of choline-precursor-supply for GB accumulation, and young
      leaves and storage root are sensitive sites for GB accumulation. 

PMID- 26302483
TI  - Decreased seed oil production in FUSCA3 Brassica napus mutant plants.
AB  - Canola (Brassica napus L.) oil is extensively utilized for human consumption and
      industrial applications. Among the genes regulating seed development and
      participating in oil accumulation is FUSCA3 (FUS3), a member of the plant
      specific B3-domain family of transcription factors. To evaluate the role of this
      gene during seed storage deposition, three BnFUSCA3 (BnFUS3) TILLING mutants were
      generated. Mutations occurring downstream of the B3 domain reduced silique number
      and repressed seed oil level resulting in increased protein content in developing
      seeds. BnFUS3 mutant seeds also had increased levels of linoleic acid, possibly
      due to the reduced expression of omega-3 FA DESATURASE (FAD3). These observed
      phenotypic alterations were accompanied by the decreased expression of genes
      encoding transcription factors stimulating fatty acid (FA) synthesis: LEAFY
      COTYLEDON1 and 2 (LEC1 and 2) ABSCISIC ACID-INSENSITIVE 3 (BnABI3) and WRINKLED1
      (WRI1). Additionally, expression of genes encoding enzymes involved in sucrose
      metabolism, glycolysis, and FA modifications were down-regulated in developing
      seeds of the mutant plants. Collectively, these transcriptional changes support
      altered sucrose metabolism and reduced glycolytic activity, diminishing the
      carbon pool available for the synthesis of FA and ultimately seed oil production.
      Based on these observations, it is suggested that targeted manipulations of
      BnFUS3 can be used as a tool to influence oil accumulation in the economically
      important species B. napus. 

PMID- 26302484
TI  - Rate and predictors of serum HCV-RNA >6 million IU/mL in patients with chronic
      hepatitis C.
AB  - BACKGROUND: Baseline serum HCV-RNA predicts sustained virological response in
      chronic hepatitis C patients treated with antiviral therapy. A threshold at 6
      million IU/mL has been proposed to best discriminate treatment outcomes on
      sofosbuvir-based regimens. In comparison with the general population,
      immunosuppressed individuals exhibit greater viral load values. OBJECTIVES: To
      estimate the rate and predictors of serum HCV-RNA above 6 millionIU/mL in chronic
      hepatitis C patients on care outside clinical trials. STUDY DESIGN: Serum HCV-RNA
      values recorded from all chronic hepatitis C patients consecutively attended at
      our clinic during the last decade were analyzed. Testing had been performed using
      the COBAS TaqMan HCV test v2.0. RESULTS: A total of 816 individuals with
      detectable serum HCV-RNA were identified. The main characteristics of this
      population were as follows: mean age 48.6 years-old; 73.4% males; mean ALT
      82.6IU/L; mean HCV-RNA 6.02logIU/mL; 80.6% HCV genotypes 1 or 4; 34.9% advanced
      liver fibrosis; 35.4% IL28B-CC alleles. HIV coinfection in 78.7%, of whom 91%
      were on antiretroviral therapy. Overall, 127 (15.6%) had serum HCV-RNA values >6
      millionIU/mL. This high viremia was found in 18.2% of HIV-positive versus 5.7% of
      HIV-negative subjects (p<0.001). In multivariate analysis, serum HCV-RNA >6
      millionIU/mL was only significantly associated with HIV coinfection (OR: 4.03;
      95% CI: 1.98-8.19, p<0.01) and HCV genotypes 1 or 4 (OR: 1.88; 95% CI: 1.05-3.37,
      p=0.03). CONCLUSIONS: Serum HCV-RNA >6 millionIU/mL is roughly seen in 6% of
      chronic hepatitis C monoinfected patients, and increases up to 18% in HIV
      coinfection.

PMID- 26302485
TI  - Towards a minimally invasive sampling tool for high resolution tissue analytical
      mapping.
AB  - Multiple spatial mapping techniques of biological tissues have been proposed over
      the years, but all present limitations either in terms of resolution, analytical
      capacity or invasiveness. Ren et al (2015 Nanotechnology 26 284001) propose in
      their most recent work the use of a picosecond infrared laser (PIRL) under
      conditions of ultrafast desorption by impulsive vibrational excitation (DIVE) to
      extract small amounts of cellular and molecular components, conserving their
      viability, structure and activity. The PIRL DIVE technique would then work as a
      nanobiopsy with minimal damage to the surrounding tissues, which could
      potentially be applied for high resolution local structural characterization of
      tissues in health and disease with the spatial limit determined by the laser
      focus. 

PMID- 26302486
TI  - Comparative Effectiveness of Medical Therapies for Severe Alcoholic Hepatitis:
      Guidance at Last?

PMID- 26302487
TI  - Reducing colorectal cancer risk among African Americans.

PMID- 26302488
TI  - Neutrophil Extracellular Traps Induce Trypsin Activation, Inflammation, and
      Tissue Damage in Mice With Severe Acute Pancreatitis.
AB  - BACKGROUND & AIMS: Neutrophils are involved in the development of acute
      pancreatitis (AP), but it is not clear how neutrophil-induced tissue damage is
      regulated. In addition to secreting antimicrobial compounds, activated
      neutrophils eliminate invading microorganisms by expelling nuclear DNA and
      histones to form extracellular web-like structures called neutrophil
      extracellular traps (NETs). However, NETs have been reported to contribute to
      organ dysfunction in patients with infectious diseases. We investigated whether
      NETs contribute to the development of AP in mice. METHODS: AP was induced in
      C57BL/6 mice by infusion of taurocholate into the pancreatic duct or by
      intraperitoneal administration of L-arginine. Pancreata were collected and
      extracellular DNA was detected by Sytox green staining, levels of CXC chemokines,
      histones, and cytokines also were measured. Cell-free DNA was quantified in
      plasma samples. Signal transducer and activator of transcription 3
      phosphorylation and trypsin activation were analyzed in isolated acinar cells.
      NETs were depleted by administration of DNase I to mice. Plasma was obtained from
      healthy individuals (controls) and patients with severe AP. RESULTS: Infusion of
      taurocholate induced formation of NETs in pancreatic tissues of mice and
      increased levels of cell-free DNA in plasma. Neutrophil depletion prevented
      taurocholate-induced deposition of NETs in the pancreas. Administration of DNase
      I to mice reduced neutrophil infiltration and tissue damage in the inflamed
      pancreas and lung, and decreased levels of blood amylase, macrophage inflammatory
      protein-2, interleukin 6, and high-mobility groups protein 1. In mice given
      taurocholate, DNase I administration also reduced expression of integrin alpha M
      (macrophage-1 antigen) on circulating neutrophils. Similar results occurred in
      mice with L-arginine-induced AP. Addition of NETs and histones to acinar cells
      induced formation of trypsin and activation of signal transducer and activator of
      transcription 3; these processes were blocked by polysialic acid. Patients with
      severe AP had increased plasma levels of NET components compared with controls.
      CONCLUSIONS: NETs form in the pancreata of mice during the development of AP, and
      NET levels are increased in plasma from patients with AP, compared with controls.
      NETs regulate organ inflammation and injury in mice with AP, and might be
      targeted to reduce pancreatic tissue damage and inflammation in patients.

PMID- 26302490
TI  - FoxC1: Novel Regulator of Inflammation-Induced Metastasis in Hepatocellular
      Carcinoma.

PMID- 26302489
TI  - Nuclear Localization of DNAJB6 Is Associated With Survival of Patients With
      Esophageal Cancer and Reduces AKT Signaling and Proliferation of Cancer Cells.
AB  - BACKGROUND & AIMS: The DnaJ (Hsp40) homolog, subfamily B, member 6 (DNAJB6) is
      part of a family of proteins that regulates chaperone activities. One of its
      isoforms, DNAJB6a, contains a nuclear localization signal and regulates beta
      catenin signaling during breast cancer development. We investigated the role of
      DNAJB6 in the pathogenesis of esophageal squamous cell carcinoma (ESCC). METHODS:
      We performed immunohistochemical analyses of primary ESCC samples and lymph node
      metastases from a cohort of 160 patients who underwent esophagectomy with no
      preoperative chemoradiotherapy at Hong Kong Queen Mary Hospital. Data were
      collected on patient outcomes over a median time of 12.1 +/- 2.9 months.
      Retrospective survival association analyses were performed. Wild-type and mutant
      forms of DNAJB6a were overexpressed in cancer cell lines (KYSE510, KYSE 30TSI,
      KYSE140, and KYSE70TS), which were analyzed in proliferation and immunoblot
      assays, or injected subcutaneously into nude mice. Levels of DNAJB6 were knocked
      down in ESCC cell lines (KYSE450 and T.Tn), immortalized normal esophageal
      epithelial cell lines (NE3 and NE083), and other cells with short hairpin RNAs,
      or by genome engineering. Bimolecular fluorescence complementation was used to
      study interactions between proteins in living cells. RESULTS: In primary ESCC
      samples, patients whose tumors had high nuclear levels of DNAJB6 had longer
      overall survival times (19.2 +/- 1.8 months; 95% confidence interval [CI], 15.6
      22.8 mo) than patients whose tumors had low nuclear levels of DNAJB6 (12.6 +/-
      1.4 mo; 95% CI, 9.8-15.4 mo; P = .004, log-rank test). Based on Cox regression
      analysis, patients whose tumors had high nuclear levels of DNAJB6 had a lower
      risk of death than patients with low levels (hazard ratio, 0.562; 95% CI, 0.379
      0.834; P = .004). Based on log-rank analysis and Cox regression analysis, the
      combination of the nuclear level of DNAJB6 and the presence of lymph node
      metastases at diagnosis could be used to stratify patients into groups with good
      or bad outcomes (P < .0005 for both analyses). There was a negative association
      between the nuclear level of DNAJB6 and the presence of lymph node metastases (P
      = .022; Pearson chi(2) test). Cancer cell lines that overexpressed DNAJB6a formed
      tumors more slowly in nude mice than control cells or cells that expressed a
      mutant form of DNAJB6a that did not localize to the nucleus. DNAJB6 knockdown in
      cancer cell lines promoted their growth as xenograft tumors in mice. A motif of
      histidine, proline, and aspartic acid in the J domain of DNAJB6a was required for
      its tumor-suppressive effects and signaling via AKT1. Loss of DNAJB6a resulted in
      up-regulation of AKT signaling in cancer cell lines and immortalized esophageal
      epithelial cells. Expression of a constitutively active form of AKT1 restored
      proliferation to tumor cells that overexpressed DNAJB6a, and DNAJB6a formed a
      complex with AKT1 in living cells. The expression of DNAJB6a reduced the
      sensitivity of ESCC to AKT inhibitors; the expression level of DNAJB6a affected
      AKT signaling in multiple cancer cell lines. CONCLUSIONS: Nuclear localization of
      DNAJB6 is associated with longer survival times of patients with ESCC. DNAJB6a
      reduces AKT signaling, and DNAJB6 expression in cancer cells reduces their
      proliferation and growth of xenograft tumors in mice. DNAJB6a might be developed
      as a biomarker for progression of ESCC.

PMID- 26302491
TI  - Effects of Electrode Material on the Voltage of a Tree-Based Energy Generator.
AB  - The voltage between a standing tree and its surrounding soil is regarded as an
      innovative renewable energy source. This source is expected to provide a new
      power generation system for the low-power electrical equipment used in forestry.
      However, the voltage is weak, which has caused great difficulty in application.
      Consequently, the development of a method to increase the voltage is a key issue
      that must be addressed in this area of applied research. As the front-end
      component for energy harvesting, a metal electrode has a material effect on the
      level and stability of the voltage obtained. This study aimed to preliminarily
      ascertain the rules and mechanisms that underlie the effects of electrode
      material on voltage. Electrodes of different materials were used to measure the
      tree-source voltage, and the data were employed in a comparative analysis. The
      results indicate that the conductivity of the metal electrode significantly
      affects the contact resistance of the electrode-soil and electrode-trunk contact
      surfaces, thereby influencing the voltage level. The metal reactivity of the
      electrode has no significant effect on the voltage. However, passivation of the
      electrode materials markedly reduces the voltage. Suitable electrode materials
      are demonstrated and recommended. 

PMID- 26302492
TI  - Identification of the Acetylation and Ubiquitin-Modified Proteome during the
      Progression of Skeletal Muscle Atrophy.
AB  - Skeletal muscle atrophy is a consequence of several physiological and
      pathophysiological conditions including muscle disuse, aging and diseases such as
      cancer and heart failure. In each of these conditions, the predominant mechanism
      contributing to the loss of skeletal muscle mass is increased protein turnover.
      Two important mechanisms which regulate protein stability and degradation are
      lysine acetylation and ubiquitination, respectively. However our understanding of
      the skeletal muscle proteins regulated through acetylation and ubiquitination
      during muscle atrophy is limited. Therefore, the purpose of the current study was
      to conduct an unbiased assessment of the acetylation and ubiquitin-modified
      proteome in skeletal muscle during a physiological condition of muscle atrophy.
      To induce progressive, physiologically relevant, muscle atrophy, rats were cast
      immobilized for 0, 2, 4 or 6 days and muscles harvested. Acetylated and
      ubiquitinated peptides were identified via a peptide IP proteomic approach using
      an anti-acetyl lysine antibody or a ubiquitin remnant motif antibody followed by
      mass spectrometry. In control skeletal muscle we identified and mapped the
      acetylation of 1,326 lysine residues to 425 different proteins and the
      ubiquitination of 4,948 lysine residues to 1,131 different proteins. Of these
      proteins 43, 47 and 50 proteins were differentially acetylated and 183, 227 and
      172 were differentially ubiquitinated following 2, 4 and 6 days of disuse,
      respectively. Bioinformatics analysis identified contractile proteins as being
      enriched among proteins decreased in acetylation and increased in ubiquitination,
      whereas histone proteins were enriched among proteins increased in acetylation
      and decreased in ubiquitination. These findings provide the first proteome-wide
      identification of skeletal muscle proteins exhibiting changes in lysine
      acetylation and ubiquitination during any atrophy condition, and provide a basis
      for future mechanistic studies into how the acetylation and ubiquitination status
      of these identified proteins regulates the muscle atrophy phenotype. 

PMID- 26302494
TI  - A Discontinuation Trial of Antihypertensive Treatment: The Other Side of the
      Story.

PMID- 26302493
TI  - A Population-Structured HIV Epidemic in Israel: Roles of Risk and Ethnicity.
AB  - BACKGROUND: HIV in Israel started with a subtype-B epidemic among men who have
      sex with men, followed in the 1980s and 1990s by introductions of subtype C from
      Ethiopia (predominantly acquired by heterosexual transmission) and subtype A from
      the former Soviet Union (FSU, most often acquired by intravenous drug use). The
      epidemic matured over the last 15 years without additional large influx of
      exogenous infections. Between 2005 and 2013 the number of infected men who have
      sex with men (MSM) increased 2.9-fold, compared to 1.6-fold and 1.3-fold for
      intravenous drug users (IVDU) and Ethiopian-origin residents. Understanding
      contemporary spread is essential for effective public health planning. METHODS:
      We analyzed demographic and virologic data from 1,427 HIV-infected individuals
      diagnosed with HIV-I during 1998-2012. HIV phylogenies were reconstructed with
      maximum-likelihood and Bayesian methods. RESULTS: Subtype-B viruses, but not A or
      C, demonstrated a striking number of large clusters with common ancestors having
      posterior probability >=0.95, including some suggesting presence of transmission
      networks. Transmitted drug resistance was highest in subtype B (13%). MSM
      represented a frequent risk factor in cross-ethnic transmission, demonstrated by
      the presence of Israeli-born with non-B virus infections and FSU immigrants with
      non-A subtypes. CONCLUSIONS: Reconstructed phylogenetic trees demonstrated
      substantial grouping in subtype B, but not in non-MSM subtype-A or in subtype-C,
      reflecting differences in transmission dynamics linked to HIV transmission
      categories. Cross-ethnic spread occurred through multiple independent
      introductions, with MSM playing a prevalent role in the transmission of the
      virus. Such data provide a baseline to track epidemic trends and will be useful
      in informing and quantifying efforts to reduce HIV transmission.

PMID- 26302495
TI  - Incidentally Identified Common Bile Duct Dilatation: A Systematic Review of
      Evaluation, Causes, and Outcome.
AB  - BACKGROUND: With the widespread use of abdominal imaging, an incidentally found
      dilated common bile duct (CBD) is a common radiographic finding. The significance
      of a dilated CBD as a predictor of underlying disease and long-term outcome have
      not been well elucidated. GOALS: A systematic review of studies on patients with
      dilated CBD was performed to identify etiologies and clinical factors that may
      predict which patients require further diagnostic testing and long-term outcomes.
      A PubMed search for relevant articles published between 2001 and 2014 was
      performed. RESULTS: The search yielded a total of 882 articles, and after careful
      individual review for eligibility and relevancy, 9 peer-reviewed studies were
      included. A cause of the CBD dilation was found on average in 33% of cases and
      the most common causes were: CBD stone, chronic pancreatitis, and periampullary
      diverticulum. The overall CBD diameter was not associated with finding a
      causative lesion. Coexisting CBD and intrahepatic bile duct dilation, age, and
      jaundice were found to be indicators of pathologic lesions. Dilation of both the
      CBD and pancreatic duct was suggestive of pancreatic disease, especially
      pancreatic malignancy in the setting of obstructive jaundice. Follow-up was
      reported in 6 studies ranging from 6 to 85 months, and generally there was no
      change in the diagnosis. CONCLUSIONS: Incidentally found biliary tract dilatation
      can be a manifestation of significant biliary tract disease including malignancy.
      Long-term outcome is not well defined and further prospective studies examining
      the most cost-effective approach to evaluation are needed.

PMID- 26302496
TI  - A Prospective, Multicenter Study of the AIMS65 Score Compared With the Glasgow
      Blatchford Score in Predicting Upper Gastrointestinal Hemorrhage Outcomes.
AB  - BACKGROUND: The AIMS65 score and the Glasgow-Blatchford risk score (GBRS) are
      validated preendoscopic risk scores for upper gastrointestinal hemorrhage (UGIH).
      GOALS: To compare the 2 scores' performance in predicting important outcomes in
      UGIH. STUDY: A prospective cohort study in 2 tertiary referral centers and 1
      community teaching hospital. Adults with UGIH were included. The AIMS65 score and
      GBRS were calculated for each patient. The primary outcome was inpatient
      mortality. Secondary outcomes were 30-day mortality, in-hospital rebleeding, 30
      day rebleeding, length of stay, and a composite endpoint of in-hospital
      mortality, transfusions, or need for intervention (endoscopic, radiologic, or
      surgical treatment). The area under the receiver operating characteristic curve
      (AUROC) was calculated for each score and outcome. RESULTS: A total of 298
      patients were enrolled. The AIMS65 score was superior to the GBRS in predicting
      in-hospital mortality (AUROC, 0.85 vs. 0.66; P<0.01) and length of stay (Somer's
      D, 0.21 vs. 0.13; P=0.04). The scores were similar in predicting 30-day mortality
      (AUROC, 0.74 vs. 0.65; P=0.16), in-hospital rebleeding (AUROC, 0.69 vs. 0.62;
      P=0.19), 30-day rebleeding (AUROC, 0.63 vs. 0.63; P=0.90), and the composite
      outcome (AUROC, 0.57 vs. 0.59; P=0.49). The optimal cutoffs for predicting in
      hospital mortality were an AIMS65 score of 3 and a GBRS score of 10. For
      predicting rebleeding, the optimal cutoffs were 2 and 10, respectively.
      CONCLUSIONS: The AIMS65 score is superior to the GBRS for predicting in-hospital
      mortality and hospital length of stay for patients with UGIH. The AIMS65 score
      and GBRS are similar in predicting 30-day mortality, rebleeding, and a composite
      endpoint.

PMID- 26302497
TI  - Endoscopic Bypass Using Endobarrier Devices: Efficacy in Treating Obesity and
      Metabolic Syndrome.
AB  - Obesity is a rapidly growing pandemic. Scope of pharmacotherapy and bariatric
      surgery in managing obesity is ever rising. The role of minimally invasive
      techniques to achieve preoperative weight loss and improve postbariatric surgery
      outcomes is an area of new interest. The initial experience with endobarrier
      devices in achieving weight loss among obese subjects has shown promising
      results. In addition, the impact of these interventions on comorbidities commonly
      associated with obesity like diabetes mellitus type 2 and hyperlipidemia has
      further expanded their potential for use in future. In this review article, we
      have summarized case report, prospective single and multicenter studies, and
      randomized-controlled trials describing the use of endobarrier devices.
      Indications, techniques, outcomes, limitations, and complications reported are
      discussed. 

PMID- 26302499
TI  - Is Mean Platelet Volume Actually Significantly Higher in Patients With
      Nonalcoholic Fatty Liver Disease?

PMID- 26302498
TI  - Insulin Resistance is Associated With Significant Liver Fibrosis in Chronic
      Hepatitis C Patients: A Systemic Review and Meta-Analysis.
AB  - BACKGROUND: The role of insulin resistance (IR) on fibrosis progression in
      hepatitis C virus (HCV) patients has not been systematically evaluated.
      Therefore, this systemic review aimed to summarize the available epidemiologic
      evidence to evaluate the strength of association between IR and advanced liver
      fibrosis in these patients. METHODS: We performed a systemic literature search in
      PubMed, OvidSP, and MEDLINE from January 1990 to April 2015 without language
      restriction using the following search terms: insulin resistance, liver fibrosis,
      cirrhosis, diabetes mellitus, and chronic hepatitis C. Publication bias was
      assessed using the Begg and Egger tests and with a visual inspection of funnel
      plot. All analyses were performed using Comprehensive Meta-Analysis, version 2
      software. RESULTS: A total of 3659 participants with HCV infection from 14
      studies were included in the analysis. After adjusting for publication bias, the
      relative risk (RR) for significant hepatic fibrosis among HCV subjects with IR
      was 1.63 [95% confidence interval (CI), 1.34-2.01]. Subgroup analysis by
      genotypes showed RR of 2.16 (95% CI, 1.52-3.06) for genotype 1; however, the
      association was no longer significant when we analyzed the data for HCV genotype
      3; RR=1.40 (95% CI, 0.8-2.45). CONCLUSION: Our study showed significant
      association between IR and significant hepatic fibrosis in patients with HCV
      genotype 1 infection.

PMID- 26302500
TI  - Immune Thrombocytopenia Caused by Fecal Microbial Transplantation in a Patient
      With Severe Recurrent Clostridium difficile Infection.

PMID- 26302501
TI  - Nitrogen-Doped Carbon Nanofiber/Molybdenum Disulfide Nanocomposites Derived from
      Bacterial Cellulose for High-Efficiency Electrocatalytic Hydrogen Evolution
      Reaction.
AB  - To remit energy crisis and environmental deterioration, non-noble metal
      nanocomposites have attracted extensive attention, acting as a fresh kind of cost
      effective electrocatalysts for hydrogen evolution reaction (HER). In this work,
      hierarchically organized nitrogen-doped carbon nanofiber/molybdenum disulfide
      (pBC-N/MoS2) nanocomposites were successfully prepared via the combination of in
      situ polymerization, high-temperature carbonization process, and hydrothermal
      reaction. Attributing to the uniform coating of polyaniline on the surface of
      bacterial cellulose, the nitrogen-doped carbon nanofiber network acts as an
      excellent three-dimensional template for hydrothermal growth of MoS2 nanosheets.
      The obtained hierarchical pBC-N/MoS2 nanocomposites exhibit excellent
      electrocatalytic activity for HER with small overpotential of 108 mV, high
      current density of 8.7 mA cm(-2) at eta = 200 mV, low Tafel slope of 61 mV dec(
      1), and even excellent stability. The greatly improved performance is benefiting
      from the highly exposed active edge sites of MoS2 nanosheets, the intimate
      connection between MoS2 nanosheets and the highly conductive nitrogen-doped
      carbon nanofibers and the three-dimensional networks thus formed. Therefore, this
      work provides a novel strategy for design and application of bacterial cellulose
      and MoS2-based nanocomposites as cost-effective HER eletrocatalysts. 

PMID- 26302502
TI  - Modeling a Conventional Electroporation Pulse Train: Decreased Pore Number,
      Cumulative Calcium Transport and an Example of Electrosensitization.
AB  - Pulse trains are widely used in electroporation (EP) for both general biomedical
      research and clinical applications such as nonthermal tumor ablation. Here we use
      a computational method based on a meshed transport network to investigate a cell
      system model's response to a train of identical, evenly spaced electric field
      pulses. We obtain an unexpected result: the number of membrane pores decreases
      during the application of twenty 1.0 kV/cm, 100 MUs pulses, delivered at 1 Hz.
      This pulse train initially creates 13,000 membrane pores, but pore number
      decreases by a factor of 15 to about 830 pores throughout subsequent pulses. We
      conclude that pore number can greatly diminish during a train of identical
      pulses, with direct consequences for the transport of solutes across an
      electroporated membrane. Although application of additional pulses is generally
      intended to increase the effects of EP, we show that these pulses do not
      significantly enhance calcium delivery into the cell. Instead, calcium delivery
      can be significantly increased by varying inter-pulse intervals. We show that
      inserting a 300-s interruption midway in a widely used eight-pulse train (a
      protocol for electrosensitization) yields a ~ twofold delivery increase. Overall,
      our modeling shows support for electrosensitization, in which multiple pulse
      protocols that maximize pore number over time can yield significant increase of
      transport of calcium compared to standard pulse trains.

PMID- 26302503
TI  - Navigated Breast Tumor Excision Using Electromagnetically Tracked Ultrasound and
      Surgical Instruments.
AB  - OBJECTIVE: Lumpectomy, breast conserving tumor excision, is the standard surgical
      treatment in early stage breast cancer. A common problem with lumpectomy is that
      the tumor may not be completely excised, and additional surgery becomes
      necessary. We investigated if a surgical navigation system using intraoperative
      ultrasound improves the outcomes of lumpectomy and if such a system can be
      implemented in the clinical environment. METHODS: Position sensors were applied
      on the tumor localization needle, the ultrasound probe, and the cautery, and 3-D
      navigation views were generated using real-time tracking information. The system
      was tested against standard wire-localization procedures on phantom breast models
      by eight surgical residents. Clinical safety and feasibility was tested in six
      palpable tumor patients undergoing lumpectomy by two experienced surgical
      oncologists. RESULTS: Navigation resulted in significantly less tissue excised
      compared to control procedures (10.3 +/- 4.4 versus 18.6 +/- 8.7 g, p = 0.01) and
      lower number of tumor-positive margins (1/8 versus 4/8) in the phantom
      experiments. Excision-tumor distance was also more consistently outside the tumor
      margins with navigation in phantoms. The navigation system has been successfully
      integrated in an operating room, and user experience was rated positively by
      surgical oncologists. CONCLUSION: Electromagnetic navigation may improve the
      outcomes of lumpectomy by making the tumor excision more accurate. SIGNIFICANCE:
      Breast cancer is the most common cancer in women, and lumpectomy is its first
      choice treatment. Therefore, the improvement of lumpectomy outcomes has a
      significant impact on a large patient population.

PMID- 26302504
TI  - Improved Heart Sound Detection and Signal-to-Noise Estimation Using a Low-Mass
      Sensor.
AB  - GOAL: The purpose of this paper is to improve the detection of high-frequency
      sounds from the heart for better identification of turbulent blood flow in
      partially occluded coronary arteries. This paper also describes a method for the
      quantitative assessment of data quality. METHODS: A very light-weight dual
      accelerometer has been developed that places a small mechanical load on the
      chest. When used in conjunction with a novel correlation-based analysis, this
      dual-signal transducer provides an estimate to the signal-to-noise ratio (SNR) of
      the acoustic signal. RESULTS: The new transducer has significantly better SNR
      properties than the traditional cardiac microphones. This improvement is due to
      increased sensitivity to high-frequency signals not a reduction in noise and is
      likely the result of reduced mechanical loading on the chest. CONCLUSION:
      Substantial improvement in the detection of high-frequency heart sounds is
      possible as is quantitative assessment of data quality. SIGNIFICANCE: The new
      transducer and analysis will lead to substantial improvements in the acoustic
      detection of partially occluded arteries associated with coronary artery disease.
      It is finally possible to obtain a measurement of the quality of heart sound
      signals as they are being recorded.

PMID- 26302505
TI  - Synthesis and Characterization of Magnetic Polyvinyl Alcohol (PVA) Hydrogel
      Microspheres for the Embolization of Blood Vessel.
AB  - GOAL: Vascular embolization has exhibited increasing significance in treatment of
      terminal cancer. In order to achieve better embolic effects, magnetic polyvinyl
      alcohol hydrogel microspheres were synthesized for magnetic field-controlled
      vascular embolization. METHODS: Inverse suspension crosslinking method was
      adopted to synthesize the magnetic hydrogel microspheres by loading magnetic
      nanoparticles inside. The magnetic property, CT angiography, drug release, and
      magnetothermal performance were characterized in vitro, respectively. The
      fluidity of microspheres was also showed by simulation and experiment in vitro.
      RESULTS: The microspheres were shown to have capability of drug loading, CT
      imaging, and magnetothermal behavior. Both the simulated and the experimental
      results exhibited that the microspheres can be controlled to aggregate in the
      fluid in the presence of magnetic field. SIGNIFICANCE: The magnetic hydrogel
      microspheres exhibited the specific fluidity-like iodized oil, but were able to
      form solid embolus. Because of the advantages of this novel material, it is
      expected to get extensive application in the clinic embolotherapy.

PMID- 26302507
TI  - Feature-Based Correlation and Topological Similarity for Interbeat Interval
      Estimation Using Ultrawideband Radar.
AB  - The objectives of this paper are to propose a method that can accurately estimate
      the human heart rate (HR) using an ultrawideband (UWB) radar system, and to
      determine the performance of the proposed method through measurements. The
      proposed method uses the feature points of a radar signal to estimate the HR
      efficiently and accurately. Fourier- and periodicity-based methods are
      inappropriate for estimation of instantaneous HRs in real time because heartbeat
      waveforms are highly variable, even within the beat-to-beat interval. We define
      six radar waveform features that enable correlation processing to be performed
      quickly and accurately. In addition, we propose a feature topology signal that is
      generated from a feature sequence without using amplitude information. This
      feature topology signal is used to find unreliable feature points, and thus, to
      suppress inaccurate HR estimates. Measurements were taken using UWB radar, while
      simultaneously performing electrocardiography measurements in an experiment that
      was conducted on nine participants. The proposed method achieved an average root
      mean-square error in the interbeat interval of 7.17 ms for the nine participants.
      The results demonstrate the effectiveness and accuracy of the proposed method.
      The significance of this study for biomedical research is that the proposed
      method will be useful in the realization of a remote vital signs monitoring
      system that enables accurate estimation of HR variability, which has been used in
      various clinical settings for the treatment of conditions such as diabetes and
      arterial hypertension. 

PMID- 26302506
TI  - Evaluation of Linear Regression Simultaneous Myoelectric Control Using
      Intramuscular EMG.
AB  - GOAL: The objective of this study was to evaluate the ability of linear
      regression models to decode patterns of muscle coactivation from intramuscular
      electromyogram (EMG) and provide simultaneous myoelectric control of a virtual 3
      DOF wrist/hand system. Performance was compared to the simultaneous control of
      conventional myoelectric prosthesis methods using intramuscular EMG (parallel
      dual-site control)-an approach that requires users to independently modulate
      individual muscles in the residual limb, which can be challenging for amputees.
      METHODS: Linear regression control was evaluated in eight able-bodied subjects
      during a virtual Fitts' law task and was compared to performance of eight
      subjects using parallel dual-site control. An offline analysis also evaluated how
      different types of training data affected prediction accuracy of linear
      regression control. RESULTS: The two control systems demonstrated similar overall
      performance; however, the linear regression method demonstrated improved
      performance for targets requiring use of all three DOFs, whereas parallel dual
      site control demonstrated improved performance for targets that required use of
      only one DOF. Subjects using linear regression control could more easily activate
      multiple DOFs simultaneously, but often experienced unintended movements when
      trying to isolate individual DOFs. Offline analyses also suggested that the
      method used to train linear regression systems may influence controllability.
      CONCLUSION AND SIGNIFICANCE: Linear regression myoelectric control using
      intramuscular EMG provided an alternative to parallel dual-site control for 3-DOF
      simultaneous control at the wrist and hand. The two methods demonstrated
      different strengths in controllability, highlighting the tradeoff between
      providing simultaneous control and the ability to isolate individual DOFs when
      desired.

PMID- 26302508
TI  - Noninvasive Estimation of Respiratory Mechanics in Spontaneously Breathing
      Ventilated Patients: A Constrained Optimization Approach.
AB  - This paper presents a method for breath-by-breath noninvasive estimation of
      respiratory resistance and elastance in mechanically ventilated patients. For
      passive patients, well-established approaches exist. However, when patients are
      breathing spontaneously, taking into account the diaphragmatic effort in the
      estimation process is still an open challenge. Mechanical ventilators require
      maneuvers to obtain reliable estimates for respiratory mechanics parameters. Such
      maneuvers interfere with the desired ventilation pattern to be delivered to the
      patient. Alternatively, invasive procedures are needed. The method presented in
      this paper is a noninvasive way requiring only measurements of airway pressure
      and flow that are routinely available for ventilated patients. It is based on a
      first-order single-compartment model of the respiratory system, from which a cost
      function is constructed as the sum of squared errors between model-based airway
      pressure predictions and actual measurements. Physiological considerations are
      translated into mathematical constraints that restrict the space of feasible
      solutions and make the resulting optimization problem strictly convex. Existing
      quadratic programming techniques are used to efficiently find the minimizing
      solution, which yields an estimate of the respiratory system resistance and
      elastance. The method is illustrated via numerical examples and experimental data
      from animal tests. Results show that taking into account the patient effort
      consistently improves the estimation of respiratory mechanics. The method is
      suitable for real-time patient monitoring, providing clinicians with noninvasive
      measurements that could be used for diagnosis and therapy optimization. 

PMID- 26302509
TI  - User-Independent Recognition of Sports Activities From a Single Wrist-Worn
      Accelerometer: A Template-Matching-Based Approach.
AB  - GOAL: To investigate the accuracy of template matching for classifying sports
      activities using the acceleration signal recorded with a wearable sensor.
      METHODS: A population of 29 normal weight and 19 overweight subjects was
      recruited to perform eight common sports activities, while body movement was
      measured using a triaxial accelerometer placed at the wrist. User- and axis
      independent acceleration signal templates were automatically extracted to
      represent each activity category and recognize activity types. Five different
      similarity measures between example signals and templates were compared:
      Euclidean distance, dynamic time warping (DTW), derivative DTW, correlation and
      an innovative index, and combining distance and correlation metrics ( Rce).
      Template-based activity recognition was compared to statistical-learning
      classifiers, such as Naive Bayes, decision tree, logistic regression (LR), and
      artificial neural network (ANN) trained using time- and frequency-domain signal
      features. Each algorithm was tested on data from a holdout group of 15 normal
      weight and 19 overweight subjects. RESULTS: The Rce index outperformed other
      template-matching metrics by achieving recognition rate above 80% for the
      majority of the activities. Template matching showed robust classification
      accuracy when tested on unseen data and in case of limited training examples. LR
      and ANN achieved the highest overall recognition accuracy  ~  85% but showed to
      be more vulnerable to misclassification error than template matching on
      overweight subjects' data. CONCLUSION: Template matching can be used to classify
      sports activities using the wrist acceleration signal. SIGNIFICANCE:
      Automatically extracted template prototypes from the acceleration signal may be
      used to enhance accuracy and generalization properties of statistical-learning
      classifiers.

PMID- 26302510
TI  - An Inverse Problems Approach to MR-EPT Image Reconstruction.
AB  - Magnetic Resonance-Electrical Properties Tomography (MR-EPT) is an imaging
      modality that maps the spatial distribution of the electrical conductivity and
      permittivity using standard MRI systems. The presence of a body within the
      scanner alters the RF field, and by mapping these alterations it is possible to
      recover the electrical properties. The field is time-harmonic, and can be
      described by the Helmholtz equation. Approximations to this equation have been
      previously used to estimate conductivity and permittivity in terms of first or
      second derivatives of RF field data. Using these same approximations, an inverse
      approach to solving the MR-EPT problem is presented here that leverages a forward
      model for describing the magnitude and phase of the field within the imaging
      domain, and a fitting approach for estimating the electrical properties
      distribution. The advantages of this approach are that 1) differentiation of the
      measured data is not required, thus reducing noise sensitivity, and 2) different
      regularization schemes can be adopted, depending on prior knowledge of the
      distribution of conductivity or permittivity, leading to improved image quality.
      To demonstrate the developed approach, both Quadratic (QR) and Total Variation
      (TV) regularization methods were implemented and evaluated through numerical
      simulation and experimentally acquired data. The proposed inverse approach to MR
      EPT reconstruction correctly identifies contrasts and accurately reconstructs the
      geometry in both simulations and experiments. The TV regularized scheme
      reconstructs sharp spatial transitions, which are difficult to reconstruct with
      other, more traditional approaches. 

PMID- 26302511
TI  - Triaging Diagnostically Relevant Regions from Pathology Whole Slides of Breast
      Cancer: A Texture Based Approach.
AB  - PURPOSE: Pathologists often look at whole slide images (WSIs) at low
      magnification to find potentially important regions and then zoom in to higher
      magnification to perform more sophisticated analysis of the tissue structures.
      Many automated methods of WSI analysis attempt to preprocess the down-sampled
      image in order to select salient regions which are then further analyzed by a
      more computationally intensive step at full magnification. Although it can
      greatly reduce processing times, this process may lead to small potentially
      important regions being overlooked at low magnification. We propose a texture
      analysis technique to ease the processing of H&E stained WSIs by triaging
      clinically important regions. METHOD: Image patches randomly selected from the
      whole tissue area were divided into smaller tiles and Gaussian-like texture
      filters were applied to them. Texture filter responses from each tile were
      combined together and statistical measures were derived from their histograms of
      responses. Bag of visual words pipeline was then employed to combine extracted
      features from tiles to form one histogram of words per every image patch. A
      support vector machine classifier was trained using the calculated histograms of
      words to be able to distinguish between clinically relevant and irrelevant
      patches. RESULT: Experimental analysis on 5151 image patches from 10 patient
      cases (65 tissue slides) indicated that our proposed texture technique out
      performed two previously proposed colour and intensity based methods with an area
      under the ROC curve of 0.87. CONCLUSION: Texture features can be employed to
      triage clinically important areas within large WSIs.

PMID- 26302512
TI  - Small Animal In Vivo X-Ray Tomosynthesis: Anatomical Relevance of the
      Reconstructed Images.
AB  - Whole body X-ray micro-Digital Tomosynthesis (micro-DT) for small animal imaging
      is introduced in this work. Such a system allows to deal with geometrical
      constraints that do not allow to use a micro-CT system as well as to reduce the
      radiological dose compared to a micro-CT scan. Data was simulated using the
      Digimouse anatomical model of the mouse with the designed system. An algebraic
      reconstruction algorithm regularized by Total Variation norm (TV) minimization
      was used to reconstruct images. Parameters for the reconstruction were optimized
      and the algorithm performance was evaluated quantitatively. High contrast tissues
      were subsequently segmented by thresholding the image. Quantitative analysis of
      the segmented domains indicates that a relevant anatomical information can
      possibly be extracted from micro-DT images. Indeed the Dice's coefficient values
      are greater than 0.8 for the segmented High Contrast Tissues compared to the
      phantom, which indicates an important overlap between the domains. The volume of
      the segmented tissues is over-estimated for the bones and skin-with 1.313 and
      1.113 ratios of the estimated over reference volumes, respectively-and under
      estimated in the case of the lungs with a 0.762 ratio. The mean point to surface
      distance is inferior to the voxel size of 400 MUm, for the three segmented
      tissues. These results are very encouraging and let us consider micro-DT as an
      alternative to micro-CT to deal with geometrical constraints. 

PMID- 26302513
TI  - Cubic Convolution Scaler Optimized for Local Property of Image Data.
AB  - A scaler is one of the most important modules in various video applications, such
      as ultra-high definition TV and scalable video systems. A variety of scaling
      techniques have been used to increase the video quality when the resolution of
      the source image has to be up- and down-scaled. Some conventional schemes exploit
      the property of local block data. Others consider the edge information of the
      data to be scaled. In this paper, we formulate a scaling problem to minimize the
      information loss resulting from the resizing process. The loss is considered in
      both the spatial and the frequency domains, and then it is minimized to optimize
      the kernel of the scaler. The simulation results show that the proposed algorithm
      reduces the information loss more than conventional schemes. When compared with
      the conventional algorithms, the proposed method outperforms those with similar
      complexity. 

PMID- 26302514
TI  - Contrast Invariant Interest Point Detection by Zero-Norm LoG Filter.
AB  - The Laplacian of Gaussian (LoG) filter is widely used in interest point
      detection. However, low-contrast image structures, though stable and significant,
      are often submerged by the high-contrast ones in the response image of the LoG
      filter, and hence are difficult to be detected. To solve this problem, we derive
      a generalized LoG filter, and propose a zero-norm LoG filter. The response of the
      zero-norm LoG filter is proportional to the weighted number of bright/dark pixels
      in a local region, which makes this filter be invariant to the image contrast.
      Based on the zero-norm LoG filter, we develop an interest point detector to
      extract local structures from images. Compared with the contrast dependent
      detectors, such as the popular scale invariant feature transform detector, the
      proposed detector is robust to illumination changes and abrupt variations of
      images. Experiments on benchmark databases demonstrate the superior performance
      of the proposed zero-norm LoG detector in terms of the repeatability and matching
      score of the detected points as well as the image recognition rate under
      different conditions. 

PMID- 26302515
TI  - Fast Translation Invariant Multiscale Image Denoising.
AB  - Translation invariant (TI) cycle spinning is an effective method for removing
      artifacts from images. However, for a method using O(n) time, the exact TI cycle
      spinning by averaging all possible circulant shifts requires O(n(2)) time where n
      is the number of pixels, and therefore is not feasible in practice. Existing
      literature has investigated efficient algorithms to calculate TI version of some
      denoising approaches such as Haar wavelet. Multiscale methods, especially those
      based on likelihood decomposition, such as penalized likelihood estimator and
      Bayesian methods, have become popular in image processing because of their
      effectiveness in denoising images. As far as we know, there is no systematic
      investigation of the TI calculation corresponding to general multiscale
      approaches. In this paper, we propose a fast TI (FTI) algorithm and a more
      general k-TI (k-TI) algorithm allowing TI for the last k scales of the image,
      which are applicable to general d-dimensional images (d = 2, 3, ...) with either
      Gaussian or Poisson noise. The proposed FTI leads to the exact TI estimation but
      only requires O(n log2 n) time. The proposed k-TI can achieve almost the same
      performance as the exact TI estimation, but requires even less time. We achieve
      this by exploiting the regularity present in the multiscale structure, which is
      justified theoretically. The proposed FTI and k-TI are generic in that they are
      applicable on any smoothing techniques based on the multiscale structure. We
      demonstrate the FTI and k-TI algorithms on some recently proposed state-of-the
      art methods for both Poisson and Gaussian noised images. Both simulations and
      real data application confirm the appealing performance of the proposed
      algorithms. MATLAB toolboxes are online accessible to reproduce the results and
      be implemented for general multiscale denoising approaches provided by the users.

PMID- 26302516
TI  - Photometric Stereo for General BRDFs via Reflection Sparsity Modeling.
AB  - This paper proposes a pixelwise photometric stereo method for object surfaces
      with general bidirectional reflectance distribution functions (BRDFs) via
      appropriate reflection modeling. The modeling is based on three general
      characteristics of reflection components, i.e., the smooth variation of diffuse
      reflection, the concentration of specular reflection, and the low-intensity
      nature of shadow. A graph, whose nodes are light directions, is introduced to
      model these characteristics. In the graph, the neighborhood of nodes is
      determined by finding the light sources with close directions. The smoothness of
      the diffuse component is termed as the summation of local variations under all
      light sources. The specular reflection is modeled by group sparsity, and the
      shadow is determined via weighted l1 -norm modeling. The optimization problem,
      which incorporates these three modeling terms, is cast as a second-order cone
      programming problem. The proposed method is evaluated on both synthetic and real
      world scenes with both isotropic and anisotropic materials. The experimental
      results show that the method is effective for object surfaces with general BRDFs
      and outperforms the state-of-the-arts. 

PMID- 26302517
TI  - Unsupervised Unmixing of Hyperspectral Images Accounting for Endmember
      Variability.
AB  - This paper presents an unsupervised Bayesian algorithm for hyperspectral image
      unmixing, accounting for endmember variability. The pixels are modeled by a
      linear combination of endmembers weighted by their corresponding abundances.
      However, the endmembers are assumed random to consider their variability in the
      image. An additive noise is also considered in the proposed model, generalizing
      the normal compositional model. The proposed algorithm exploits the whole image
      to benefit from both spectral and spatial information. It estimates both the mean
      and the covariance matrix of each endmember in the image. This allows the
      behavior of each material to be analyzed and its variability to be quantified in
      the scene. A spatial segmentation is also obtained based on the estimated
      abundances. In order to estimate the parameters associated with the proposed
      Bayesian model, we propose to use a Hamiltonian Monte Carlo algorithm. The
      performance of the resulting unmixing strategy is evaluated through simulations
      conducted on both synthetic and real data. 

PMID- 26302518
TI  - Adding Real-Time Bayesian Ranks to Error-Related Potential Scores Improves Error
      Detection and Auto-Correction in a P300 Speller.
AB  - Brain-computer interface (BCI) spellers could improve access to communication for
      people with profound physical disabilities; however, improved speed and accuracy
      of these spellers is required to make them practical for everyday use. Here we
      introduce the combination of P300-speller confidence with the error-related
      potential (ErrP) to improve online single-trial error detection and correction
      accuracies in a BCI speller. First, we present a mechanism for obtaining P300
      confidence using a real-time Bayesian dynamic stopping framework that makes novel
      use of additional stimuli that occur due to epoch and filter delays. Second, we
      propose an ensemble of decision trees to combine ErrP and P300-confidence
      features. Third, we describe the unique attentional differences between error and
      correct feedback in our spelling interface and discuss how these differences
      affect ErrP physiology. We tested online error detection on 11 typically
      developed adults using a BCI system trained on a previous day and found an
      average sensitivity of 86.67% and specificity of 96.59%. Automatic correction
      increased selection accuracy by 13.67% and utility grew by a factor of 4.48. We
      found, however, that the improved performance was primarily attributable to the
      inclusion of P300 confidence in error detection, calling into question the
      significance of single-trial ErrP detection. 

PMID- 26302520
TI  - Infrared Fluorescence-Based Cancer Screening Capsule for the Small Intestine.
AB  - Infrared fluorescence endoscopy (IRFE), in conjunction with an infrared
      fluorescent-labelling contrast agent, is a well known technique used for
      efficient early-stage cancer detection. In this paper we present a cost-effective
      (< $500) screening capsule prototype, which is able to detect infrared (IR)
      fluorescence emitted by indocyanine green (ICG) fluorophore dye. Rather than
      image, the capsule works as a high-sensitivity fluorometer that records
      fluorescence levels throughout the small intestine. The presented mixed-signal
      system has a small size, consumes very little power (~ 6.3 mA) and does not
      require an external belt and hardware for data collection. By determining
      fluorescence levels in the intestine, rather than collecting images, we avoid the
      need for labour intensive video analysis. The whole system is contained within a
      compact ingestible capsule, that is sized so as to come into close contact with
      the intestine walls during peristalsis. Ex-vivo experiments, on ICG-impregnated
      swine intestine, have shown that the prototype system is able to detect low
      concentrations of ICG in the nanomolar and micromolar region, which is required
      to detect early cancer in the small intestine.

PMID- 26302519
TI  - A Boosting-Based Spatial-Spectral Model for Stroke Patients' EEG Analysis in
      Rehabilitation Training.
AB  - Studies have shown that a motor imagery electro encephalogram (EEG)-based brain
      computer interface (BCI) system can be used as a rehabilitation tool for stroke
      patients. Efficient classification of EEG from stroke patients is fundamental in
      the BCI-based stroke rehabilitation systems. One of the most successful
      algorithms for EEG classification is the common spatial patterns (CSP). However,
      studies have reported that the performance of CSP heavily relies on its
      operational frequency band and channels configuration. To the best of our
      knowledge, there is no agreed upon clinical conclusion about motor imagery
      patterns of stroke patients. In this case, it is not available to obtain the
      active channels and frequency bands related to brain activities of stroke
      patients beforehand. Hence, for using the CSP algorithm, we usually set a
      relatively broad frequency range and channels, or try to find subject-related
      frequency bands and channels. To address this problem, we propose an adaptive
      boosting algorithm to perform autonomous selection of key channels and frequency
      band. In the proposed method, the spatial-spectral configurations are divided
      into multiple preconditions, and a new heuristic supervisor of stochastic
      gradient boost strategy is utilized to train weak classifiers under these
      preconditions. Extensive experiment comparisons have been performed on three
      datasets including two benchmark datasets from the famous BCI competition III and
      BCI competition IV as well as one self-acquired dataset from stroke patients.
      Results show that our algorithm yields relatively higher classification
      accuracies compared with seven state-of-the-art approaches. In addition, the
      spatial patterns (spatial weights) and spectral patterns (bandpass filters)
      determined by the algorithm can also be used for further analysis of the data,
      e.g., for brain source localization and physiological knowledge exploration. 

PMID- 26302521
TI  - Robust Low-Rank Tensor Recovery With Regularized Redescending M-Estimator.
AB  - This paper addresses the robust low-rank tensor recovery problems. Tensor
      recovery aims at reconstructing a low-rank tensor from some linear measurements,
      which finds applications in image processing, pattern recognition, multitask
      learning, and so on. In real-world applications, data might be contaminated by
      sparse gross errors. However, the existing approaches may not be very robust to
      outliers. To resolve this problem, this paper proposes approaches based on the
      regularized redescending M-estimators, which have been introduced in robust
      statistics. The robustness of the proposed approaches is achieved by the
      regularized redescending M-estimators. However, the nonconvexity also leads to a
      computational difficulty. To handle this problem, we develop algorithms based on
      proximal and linearized block coordinate descent methods. By explicitly deriving
      the Lipschitz constant of the gradient of the data-fitting risk, the descent
      property of the algorithms is present. Moreover, we verify that the objective
      functions of the proposed approaches satisfy the Kurdyka-Lojasiewicz property,
      which establishes the global convergence of the algorithms. The numerical
      experiments on synthetic data as well as real data verify that our approaches are
      robust in the presence of outliers and still effective in the absence of
      outliers.

PMID- 26302522
TI  - Single Anisotropic 3-D MR Image Upsampling via Overcomplete Dictionary Trained
      From In-Plane High Resolution Slices.
AB  - In magnetic resonance (MR), hardware limitation, scanning time, and patient
      comfort often result in the acquisition of anisotropic 3-D MR images. Enhancing
      image resolution is desired but has been very challenging in medical image
      processing. Super resolution reconstruction based on sparse representation and
      overcomplete dictionary has been lately employed to address this problem;
      however, these methods require extra training sets, which may not be always
      available. This paper proposes a novel single anisotropic 3-D MR image upsampling
      method via sparse representation and overcomplete dictionary that is trained from
      in-plane high resolution slices to upsample in the out-of-plane dimensions. The
      proposed method, therefore, does not require extra training sets. Abundant
      experiments, conducted on simulated and clinical brain MR images, show that the
      proposed method is more accurate than classical interpolation. When compared to a
      recent upsampling method based on the nonlocal means approach, the proposed
      method did not show improved results at low upsampling factors with simulated
      images, but generated comparable results with much better computational
      efficiency in clinical cases. Therefore, the proposed approach can be efficiently
      implemented and routinely used to upsample MR images in the out-of-planes views
      for radiologic assessment and postacquisition processing.

PMID- 26302523
TI  - A Smartphone-Based Tool for Assessing Parkinsonian Hand Tremor.
AB  - The aim of this study is to propose a practical smartphone-based tool to
      accurately assess upper limb tremor in Parkinson's disease (PD) patients. The
      tool uses signals from the phone's accelerometer and gyroscope (as the phone is
      held or mounted on a subject's hand) to compute a set of metrics which can be
      used to quantify a patient's tremor symptoms. In a small-scale clinical study
      with 25 PD patients and 20 age-matched healthy volunteers, we combined our
      metrics with machine learning techniques to correctly classify 82% of the
      patients and 90% of the healthy volunteers, which is high compared to similar
      studies. The proposed method could be effective in assisting physicians in the
      clinic, or to remotely evaluate the patient's condition and communicate the
      results to the physician. Our tool is low cost, platform independent,
      noninvasive, and requires no expertise to use. It is also well matched to the
      standard clinical examination for PD and can keep the patient "connected" to his
      physician on a daily basis. Finally, it can facilitate the creation of anonymous
      profiles for PD patients, aiding further research on the effectiveness of
      medication or other overlooked aspects of patients' lives. 

PMID- 26302524
TI  - A Parallel Sliding Region Algorithm to Make Agent-Based Modeling Possible for a
      Large-Scale Simulation: Modeling Hepatitis C Epidemics in Canada.
AB  - Agent-based models (ABMs) are computer simulation models that define interactions
      among agents and simulate emergent behaviors that arise from the ensemble of
      local decisions. ABMs have been increasingly used to examine trends in infectious
      disease epidemiology. However, the main limitation of ABMs is the high
      computational cost for a large-scale simulation. To improve the computational
      efficiency for large-scale ABM simulations, we built a parallelizable sliding
      region algorithm (SRA) for ABM and compared it to a nonparallelizable ABM. We
      developed a complex agent network and performed two simulations to model
      hepatitis C epidemics based on the real demographic data from Saskatchewan,
      Canada. The first simulation used the SRA that processed on each postal code
      subregion subsequently. The second simulation processed the entire population
      simultaneously. It was concluded that the parallelizable SRA showed computational
      time saving with comparable results in a province-wide simulation. Using the same
      method, SRA can be generalized for performing a country-wide simulation. Thus,
      this parallel algorithm enables the possibility of using ABM for large-scale
      simulation with limited computational resources.

PMID- 26302525
TI  - Adaptive Fuzzy Control of Strict-Feedback Nonlinear Time-Delay Systems With
      Unmodeled Dynamics.
AB  - In this paper, an approximated-based adaptive fuzzy control approach with only
      one adaptive parameter is presented for a class of single input single output
      strict-feedback nonlinear systems in order to deal with phenomena like nonlinear
      uncertainties, unmodeled dynamics, dynamic disturbances, and unknown time delays.
      Lyapunov-Krasovskii function approach is employed to compensate the unknown time
      delays in the design procedure. By combining the advances of the hyperbolic
      tangent function with adaptive fuzzy backstepping technique, the proposed
      controller guarantees the semi-globally uniformly ultimately boundedness of all
      the signals in the closed-loop system from the mean square point of view. Two
      simulation examples are finally provided to show the superior effectiveness of
      the proposed scheme.

PMID- 26302526
TI  - Dynamic Scene Classification Using Redundant Spatial Scenelets.
AB  - Dynamic scene classification started drawing an increasing amount of research
      efforts recently. While existing arts mainly rely on low-level features, little
      work addresses the need of exploring the rich spatial layout information in
      dynamic scene. Motivated by the fact that dynamic scenes are characterized by
      both dynamic and static parts with spatial layout priors, we propose to use
      redundant spatial grouping of a large number of spatiotemporal patches, named
      scenelet, to represent a dynamic scene. Specifically, each scenelet is associated
      with a category-dependent scenelet model to encode the likelihood of a specific
      scene category. All scenelet models for a scene category are jointly learned to
      encode the spatial interactions and redundancies among them. Subsequently, a
      dynamic scene sequence is represented as a collection of category likelihoods
      estimated by these scenelet models. Such presentation effectively encodes the
      spatial layout prior together with associated semantic information, and can be
      used for classifying dynamic scenes in combination with a standard learning
      algorithm such as k -nearest neighbor or linear support vector machine. The
      effectiveness of our approach is clearly demonstrated using two dynamic scene
      benchmarks and a related application for violence video classification. In the
      nearest neighbor classification framework, for dynamic scene classification, our
      method outperforms previous state-of-the-arts on both Maryland "in the wild"
      dataset and "stabilized" dynamic scene dataset. For violence video classification
      on a benchmark dataset, our method achieves a promising classification rate of
      87.08%, which significantly improves previous best result of 81.30%. 

PMID- 26302527
TI  - [Abstracts of the 58th Annual Meeting of the Japanese Society of Nephrology. June
      5-7, 2015. Nagoya, Japan].

PMID- 26302528
TI  - [Abstracts of the 26th Annual Meeting of the Association for Rapid Method and
      Automation in Microbiology. July 26, 2014. Okayama, Japan].

PMID- 26302529
TI  - [Abstracts of the 119th Annual Meeting of the Japanese Ophthalmological Society.
      April 16-19, 2015. Sapporo, Japan].

PMID- 26302530
TI  - [Abstracts of the 79th Eastern Regional Meeting of the Japanese Urological
      Association. October 12-14, 2014. Yokohama, Japan].

PMID- 26302531
TI  - [Abstracts of the 116th Congress of the Japanese Society of Otolaryngology. May
      20-23, 2015. Tokyo, Japan].

PMID- 26302532
TI  - [Abstracts of the Workshop of the Japanese Urological Association. August 21-23,
      2014. Fukuoka, Japan].

PMID- 26302533
TI  - [Abstract of the 2014 joint meeting of the Japanese Medical Society of Alcohol,
      Nicotine and Drug Addiction. Yokohama, Japan. October 3-4, 2014].

PMID- 26302534
TI  - [Abstract of the 71st annual meeting of the Japanese Society of radiological
      technology. Yokohama, Japan. April 16-19, 2015].

PMID- 26302535
TI  - [Abstracts of the 54th Annual Meeting of the Japanese Society of Nuclear
      Medicine. November 6-8, 2014. Osaka, Japan].

PMID- 26302536
TI  - [Abstracts of the 57th Annual Meeting of the Japanese Society of Child Neurology.
      May 28-30, 2015. Osaka, Japan].

PMID- 26302537
TI  - Abstracts of the XIXth World Congress for the Study of Hypertension in Pregnancy
      Preeclampsia/Hypertension - Future Risks and Novel Therapies, October 26-29,
      2014, New Orleans, Louisiana.

PMID- 26302538
TI  - Prenatal screening with microarray technology.

PMID- 26302540
TI  - "Big Data" and the CBC-diff.

PMID- 26302539
TI  - The evolution of prenatal genetic screening.

PMID- 26302541
TI  - Mobile solutions in today's Hematology lab.

PMID- 26302542
TI  - Fecal calprotectin: an inflammatory biomarker with emerging importance in the
      clinical laboratory.

PMID- 26302543
TI  - Bundled payments can shape the financial futures of pathologists and clinical
      laboratories.

PMID- 26302544
TI  - Germ-line gene therapy: making the case for embryonic mitochondrial modification.

PMID- 26302545
TI  - The challenges of MDx on FFPE tissue.

PMID- 26302546
TI  - Automation in the blood bank: the machines and the people.

PMID- 26302547
TI  - Toward a culture shift in laboratory quality: application of the full ISO 15189
      standard.

PMID- 26302548
TI  - Platelet function: beyond hemostasis--where does the lab fit in?

PMID- 26302549
TI  - [ACTUAL PROBLEMS OF HYGIENE SCIENCE AND PRACTICE IN THE PRESERVATION OF PUBLIC
      HEALTH].
AB  - In the article there are designated the state and actual hygiene tasks on the
      issue of environmental pollution and its effects on health of the population.
      There was emphasized the growing importance of chemical contamination of various
      objects of environment--air water, soil, and living environment. There is
      presented the analysis of data on different types of treatment of municipal waste
      in selected countries. There were shown the significance of the developed
      Guidance on risk assessmentfor public health as a toolfor making sound management
      decisions, prospects of using of the methodology of epidemiological mapping based
      on geoinformational technology (GIS technology). There was marked an important
      role of the younger generation of hygienists and health officers in further work
      on both preservation and improvement the health of the population in their
      countries, harmonization of scientific and practical solutions of actual problems
      of hygiene.

PMID- 26302550
TI  - [PHYSICAL ENVIRONMENTAL FACTORS IN THE ECOLOGY OF THE BRAIN].
AB  - On the base of the consideration and analysis of the performed for nearly half a
      century, numerous multifaceted experimental and field studies of biological
      action of an array of physical environmental factors and determination of their
      ecological and hygienic values there are presented are some thoughts on the
      theoretical understanding of possible mechanisms of the emergence of
      corresponding biological effects of such exposure. There are proposed
      methodological approaches to scientific substantiation for rules, regulations for
      the severity of physical factors in the environment, and there are presented
      examples of their legislative establishment and official use.

PMID- 26302551
TI  - [ON PREVENTION OF CYSTIC ECHINOCOCCOSIS IN THE REPUBLIC OF BASHKORTOSTAN].
AB  - According to official statistics, in the Republic of Bashkortostan (RB) since
      1991 there is noted the increase in the number of patients with cystic
      echinococcosis. In 2012, the number of recorded cases increased by 55.3% if
      compared with 2007. In the areas of RB, where there was observed the high index
      of population morbidity rate, there was noted the extensive growth of the
      infestation in sheep. The analysis of the landscape-climatic and sanitary
      characteristics of the territory of the RB, as well as population economic
      activity revealed a definite relationship between them and the spread of
      echinococcosis. The performed survey of rural residents of RB showed that the
      population is poorly informed about the factors of transmission and ways of
      infection by echinococcosis. Out of respondents 73% were wrong in determining
      factors of transmission of infection, 34% admitted irregularities in the disposal
      of slaughtering condemned products. Fully correct answers were given only by 9%
      of respondents. The research of fruitfulness of hydatid bubbles and viability of
      Protoscolexes revealed that the effect of hot water (t = 90-100  degrees  C) is
      effective for disinfecting of invasive origins of larvocysts. Due to the low
      level of awareness of the population there is needed an active health education
      work on effective measures to prevent the spread of echinococcosis in RB--the
      prevention of feeding dogs with raw slaughtering waste and decontamination in the
      private courtyard slaughtering condemned products with the hot water.

PMID- 26302552
TI  - [THE DYNAMICS OF THE MORBIDITY RATE OF HEMORRHAGIC FEVER WITH RENAL SYNDROME IN
      THE POPULATION OF THE CITY OF NABEREZHNYE CHELNY].
AB  - In the article there are considered the environmental and biological
      prerequisites for the dynamics of hemorrnagic fever with renal syndrome (HFRS)
      morbidity rate in the population of the city of Naberezhnye Chelny and the
      municipal districts located in the north-eastern part of the Republic of
      Tatarstan, a subdivision of Russian Federation. The territory of the Republic of
      Tatarstan is included into the body of Volga Federal District of the Russian
      Federation and is located within the boundaries in coniferous taiga and temperate
      forests, forest-steppe and steppe geographical areas. The endowment of large
      forests as well as weather and climatic conditions play an important role in the
      activity and rhythmicity of this natural focal viral infection, the virus
      carriers of which are mouse-like rodents. The virus belongs to the family
      Bunyaviridae and is a representative of the genus Hantavirus. On the base of the
      epidemiological and clinical data of State Autonomous Healthcare Institution
      "Naberezhno-Chelninskaya Infectious Diseases Hospital" there was performed the
      analysis of seasonal and the long-term HFRS morbidity rate from 2008 to 2012 with
      consideration of age and gender cohorts during the period from 2008 to 2012.
      There were shown both the seasonal character of the development of infectious
      disease and its unstable rhythmicity in the long-term dynamics. The most number
      of cases was observed in the summer-autumn period. 84,32% out of all disease
      cases were occurred in the male population, adults' morbidity rate was averagely
      28 times more than the children's morbidity rate, which was due to the more
      frequent stay in the foci of the virus circulation. In the long-term dynamics the
      fever development is indirectly related with the weather and climate conditions
      of the whole region that influence on biology and the dynamics of rodents'
      population. So 2010 was differed by anomalously hot summer that led to a
      significant reduction in the number of the disease cases among the human
      population of the area.

PMID- 26302553
TI  - [EVALUATION OF THE AIR POLLUTION HEALTH RISK FOR THE POPULATION OF THE CITY OF
      UFA].
AB  - There are presented results of the calculation of carcinogenic and non
      carcinogenic risks due to the impact of chemical air pollutants for the human
      health of a large industrial city. Maximal levels of carcinogenic hazards under
      inhalation route of substances from the air were established to be noted on
      gasoline, manganese, sulfur dioxide, copper oxide, formaldehyde. In the formation
      of carcinogenic risk the greatest contribution is made by chromium, gasoline,
      formaldehyde, benzol. The risk of non-carcinogenic and carcinogenic effects for
      the population of the city continues to remain to be high, that requires the
      development and implementation of planned recreational measures.

PMID- 26302554
TI  - [HEALTH LOSSES FROM MYOCARDIAL INFARCTION CAUSED BY AIR CHEMICAL POLLUTION OF THE
      INDUSTRIAL CENTRE].
AB  - Losses of health from myocardial infarction in the city of Kemerovo were
      estimated accordingly to the disability-adjusted life year (DALY) index, as well
      as its compartments: YLL (years lost due to premature death) and YLD (years lost
      disability). When ranking districts of the city of Kemerovo both in terms of
      chemicals exposure and the value of the DALY index there was revealed the
      opposite direction of these indices. The performance of the correlation analysis
      of health losses with concentrations of chemical contaminants allowed to reveal a
      feedback between them among the elderly patients (60 years and older) and direct-
      in young (up to 45 years old) cases. This fact probably may attest to the
      significant contribution of the environmental pollution in the process of
      development and progression of atherosclerotic changes in the young population.

PMID- 26302555
TI  - [THE HYGIENIC CONDITIONS OF THE INTERNAL ENVIRONMENT OF SYLVINITE CHAMBERS OF
      VARIOUS MODIFICATIONS].
AB  - The performed comparative physiological-hygienic assessment of the conditions of
      the internal environment of salt sylvinite structures allowed to establish the
      complex of physical factors that have a favorable influence on the functional
      condition of the basic systems of the organism of patients.

PMID- 26302556
TI  - [AIR POLLUTIONS AS A RISK FACTOR FOR THE POPULATION HEALTH IN KAZAN CITY].
AB  - In the paper there are presented data on the hygienic evaluation of the air
      pollution in the city of Kazan as a risk factor for the public health. The
      largest contribution to the air pollution in the city of Kazan was shown to be
      endowed by vehicles. The proportion of vehicle emissions in total emissions in
      the city in 2012 amounted to 71.4%. According to monitoring data the average
      annual concentrations of pollutant substances in 2012 exceeded the hygienic
      standards for benzo (a) pyrene--in 2.5 times, soot--2.2 times, nitrogen dioxide-
      1.8 times, formaldehyde--1.7 times. The risk of inhalation exposure is assessed
      as high, the greatest contribution to the risk is contributed by suspended matter
      PM2.5, soot and nitrogen dioxide.

PMID- 26302557
TI  - [DEONTOLOGICAL ISSUES IN RAILWAY HYGIENE].
AB  - There are presented the main ethical and deontological problems encountered in
      practice and research activities of the hygienist in transport. There is shown
      the importance of strict compliance with hygienic standards, disregard for the
      principle of "technical attainability", the necessity of continuous training,
      improvement of skills of sanitary-educational activity and readiness to solve
      emerging ethical issues in connection with the development of scientific and
      technical progress.

PMID- 26302558
TI  - [THE INFLUENCE OF SHIFT WORK ON WORKER'S HEALTH STATUS (REVIEW)].
AB  - The article provides an overview of domestic and foreign works on the impact of
      the replaceable labor on the efficiency, general state of health, the health and
      the dream of workers. Many hours shifts and overtime work were found to disturb
      likely familiar rhythms (sleep, wakefulness, performance), change the metabolic
      and hormonal metabolisms, reducing the recovery period between duties, contribute
      to more rapid development of fatigue. The consequence of circadian dyschrony may
      be the development of diseases of the cardiovascular system and cancer incidence.
      Studies have shown that sleep disorders are associated with metabolic changes,
      and particularly, obesity. In persons working in shifts, there are more often
      registered as individual features of the metabolic syndrome and the whole
      syndrome. It is noted that persons forming this group are at higher risk of
      developing diseases of the gastrointestinal tract. Thus, the problem of shift
      work is presented to be very important. Knowledge of ways and mechanisms that
      explain the impact of shift work on health is necessary to evaluate the
      professional risk. In the system of health measures the attention should be given
      to the rationalization of work and rest regimens, prevention of fatigue, struggle
      with sleep disorders and obesity.

PMID- 26302559
TI  - [INFLUENCE OF ENVIRONMENT FACTORS ON THE MORBIDITY RATE WITH TEMPORARY DISABILITY
      OF WORKING IN OIL REFINERY WORKERS].
AB  - There was performed a comprehensive assessment of working conditions of refinery
      workers on the results of the carrying out of certification of workplaces on
      working conditions. An analysis of the sample materials laboratory control over
      the content of harmful substances in the working area of industrial premises
      refinery. The prolonged exposure to harmful factors on the health ofworkers of
      the main production throughout the length of service was established to be a
      major riskfactor for the development of somatic and malignant diseases, to the
      gain in the morbidity rate and can become a cause of the emergency of
      malignancies.

PMID- 26302560
TI  - [HEALTH STATUS OF ELECTROTECHNICAL PERSONNEL EXPOSED TO THE COMBINED IMPACT OF
      ELECTROMAGNETIC FIELDS OF 50 HZ AND CHEMICALS].
AB  - There was performed an analysis of the working conditions and health status of
      workers of the chemical enterprise. In male electrical staff exposed to
      electromagnetic fields (EMF) of 50 Hz and chemicals, according to data of
      periodic medical examinations there was revealed statistically higher incidence
      of cardiovascular diseases and autonomic disorders. The obtained preliminary
      results allow to suggest the upsurge of the involvement of the autonomic nervous
      system in response to the combined effects of EMF of 50 Hz and chemicals.

PMID- 26302561
TI  - [PLUTONIUM AND LIFETIME REDUCTION AMONG PROFESSIONAL WORKERS FSUE].
AB  - The objective of the study is the assessment of lifetime in the cohort of Mayak
      PA workers employed in 1948-1958 and exposed to incorporated Pu-239. The decrease
      of age at death 5.2 years among males and 6.6 years among females, and after the
      start of work--6.9 years among males and 7.7 years among females, with the
      increase of Pu-239 incorporation was shown. The association of the raised
      mortality rate from tumour causes is shown both among males and females, mainly
      due to malignant neoplasms of lung and live; which are organs of Pu-239 main
      deposition. For the first time related to Pu-239 incorporation decrease of age at
      death from tumour and non-tumour causes of main and secondary organs of
      deposition both among males and females was revealed. To assess the reduction of
      lifetime Years of Potential Life Lost (YPLL) were calculated per 10(5) person
      years of potential life based on European gender standard. The calculations based
      on the obtained estimations showed significant dependence of YPLL on the level of
      Pu-239 incorporation. At that the main contribution to the increase of YPLL, i.e.
      to lifetime reduction, was due to radiation-induced decrease of the age at death
      as compared to radiation-induced increase of mortality rates.

PMID- 26302562
TI  - [HYGIENIC ASSESSMENT OF WORKING CONDITIONS IN MODERN PETROCHEMICAL INDUSTRY].
AB  - In the paper there are reported the results of the performance of hygiene
      assessment of working conditions in petrochemical industry. The studies have
      shown that workers' body is exposed to a complex of hazardous occupational
      factors including a chemical factor, noise, the severity and intensity of the
      working process. An overall assessment of working conditions corresponds to Class
      3.3.

PMID- 26302563
TI  - [MICROCLIMATE CONDITION IN SUBWAY CARS IN THE SUMMER PERIOD OF THE YEAR].
AB  - There are presented the results of the work, which aims to identify the
      relationship between the temperature of air in the salons of subway cars from the
      heat output of passengers in different people occupancy of cars during "peak
      hours", and to determine the efficacy offorced air handling regular ventilation
      or air conditioning system to remove the elevated heat load on passengers. In the
      work there was used the method of calculating the amount of heat output of 215
      passengers (nominal fullness of the chamber) and the simulation method of heat
      and moisture output of the same number of passengers. The operating system of
      ventilation has been shown to fail to decline the average temperature of the air
      in the passenger compartment to the optimum values and most efficient approach
      for the reducing the heat load on the passengers is the use of air conditioning
      systems.

PMID- 26302564
TI  - [THE STUDY OF THE SEVERITY OF EXAM STRESS AND FACTORS WHICH DETERMINE IT IN OLDER
      SCHOOLCHILDREN].
AB  - The study was performed with the help of a questionnaire of views of senior
      schoolchildren about the objectivity and stressfulness of various forms of the
      control of knowledge, the level of stress in the exams and measures for its
      reduction. 53.4% out of the students assess their knowledge in this area as
      insufficient. The most objective form of the control students consider an oral
      exam, the least stressful--blank testing. After passing the exams in class 9 we
      observed the evident reduction of representations of the objectivity of test
      forms of control. The necessity of the activization of educational work with
      students on the issues of prevention of exam stress and methodological work on
      perfection of the organization and content of the forms of Knowledge control is
      showed.

PMID- 26302565
TI  - [STUDY OF THE INFLUENCE OF MINERAL FERTILIZERS ON THE NEONATAL MORBIDITY RATE IN
      INFANTS WITH CONGENITAL MALFORMATIONS (CM) IN THE BELGOROD REGION].
AB  - Results of the performed study showed that the use of mineral fertilizers for
      crops increases the risk of morbidity in neonates with congenital malformations
      (CM). P-elevated levels of relative environmental risk is established for:
      anomalies of the musculoskeletal system, multiple congenital malformations, the
      CM as a whole. Maximum environmental risk in the conditions of high load
      offertilizers on farmland is established for congenital abnormalities of the
      development of reproductive system in newborn infants (RR = 2,76).

PMID- 26302566
TI  - [THE STATE OF HAEMODYNAMIC INDICES IN FIRST-GRADE PUPILS DURING THE ADAPTATION TO
      SCHOOL].
AB  - For the determination of haemodynamic indices during the period of in adaptation
      in children there was examined 271 schoolboy from the gymnasium of the city of
      Krasnoyarsk There was studied the dynamics of haemodynamic indices in the course
      of adaptation, there were detected the degree of influence of haemodynamic
      indices on the process of adaptation, there were revealed features of
      haemodynamic indices in children with the various forecast of a course of
      adaptation. Children with the unfavorable forecast of adaptation to school had
      according to data of cardiorhythmography (CRG) low values of power in a range of
      slow waves during the period of restoration of the orthostatic test that
      testifies to the raised tone of sympathetic nervous system. There were
      established the correlation interrelationships of the forecast of adaptation of
      children to school with changed (raised, lowered) level of arterial pressure and
      Robinson's index value.

PMID- 26302567
TI  - [ASSESSMENT OF THE QUALITY OF INFORMATION ON THE HEALTH OF CHILDREN IN RUSSIA:
      INTERREGIONAL COMPARISONS AND CLASSIFICATION].
AB  - The high level of children health, according to official statistics, (about 80%
      of children of I and II health groups), raises doubts in quality of information.
      Analytical methods of processing of databases of the official state statistics,
      based on interregional comparisons, and also comparison of the main indices of
      public children's health and multidimensional classifications are offered As a
      result of the hierarchical cluster analysis of the main indices of children's
      health the poor quality of medical examinations and health survey is confirmed.
      The best situation concerning children's health and quality of information is
      noted in 19 regions, mostly European part of the country, the worst--in six
      national regions of the North Caucasian, Southern and Siberian Federal Districts.

PMID- 26302568
TI  - [MODERN TRENDS IN THE PHYSICAL DEVELOPMENT AND THE STATE OF THE CARDIOVASCULAR
      SYSTEM IN YOUNG MEN OF THE CITY OF MAGADAN].
AB  - In the conditions of the northern region there was performed the comparative
      study of indices of the physical development and state of the cardiovascular
      system in young male European subjects, born in the city of Magadan in the 1-2
      generation over a period from 2004 to 2013. The main tendencies of physical
      development ofyoung male subjects in the city of Magadan were established to be
      the ongoing acceleration of growth process, asthenization and dysharmonization of
      the somatotype. It was determined increase of systolic and diastolic pressure
      during the last decade. Confirmed changes of cardiohemodynamics data on the back
      of aggravation of physical development and ongoing somatotype asthenization were
      shown by young male subjects, born in 90-ies of the last century. It was revealed
      that over the past 10 years there has been an increase in systolic and diastolic
      blood pressure indices. Established by us the changes in the indices of cardiac
      hemodynamics on the background of deteriorating physical development and ongoing
      asthenization of the somatotype appeared to be more pronounced in young men born
      in the 90-ies of the last century.

PMID- 26302569
TI  - [THE DYNAMICS OF INDICATORS OF ANTHROPOMETRIC SIGNS OF NEWBORN CHILDREN IN
      NIZHNEVARTOVSK FROM 1990 TO 2011].
AB  - There were studied anthropometric data of newborn infants and their dynamics from
      1990 to 2011. There was evaluated the distribution of infants according to five
      criteria: body weight and length, head, chest and abdomen circumference. There is
      done the characteristic of the set of anthropometric signs of mothers. In the
      middle of the studied period investigated parameters of infants were shown to be
      lower than at the beginning and the end, which might be due to the decrease in
      the proportion of repeated births, to the aggravation ofanthropogenic pollution
      and with the deterioration of the socio-economic situation.

PMID- 26302570
TI  - [RISK ASSESSMENT TO HEALTH OF THE POPULATION OF BURIATIIA IN CONNECTION WITH THE
      CONSUMPTION OF FOODSTUFF].
AB  - Evaluation of the risk associated with contamination of food products coming to
      the population of the Republic of Buryatia, was performed on the basis of data on
      the content of contaminants in basic food products and results of the
      questionnaire survey of the adult population. There are considered groups with
      taking into account gender differences and dietary preferences. Hazard index of
      chemical impact of non-carcinogenic substances coming from the food, in the
      surveyed individuals with predominance of lipid-protein diet is on the border of
      the permissible level (HI = 1,06-1,18). There are most probable effects of
      negative impact of toxicants with a significant proportion of the diet of
      imported products: in females--on the endocrine system (HI = 1.27-2.83), central
      (HI = 1.35) and the autonomic nervous system (HI = 1.29); in males--on the
      endocrine system (HI = 2.7). Carcinogenic risks are in the second range (more
      than 1 case per 10,000 people), the main contribution (62.2-78.9%) into the
      number of additional cases of malignant tumors among the population of the
      Republic of Buryatia is made by cadmium.

PMID- 26302571
TI  - [KEEPING THE ELECTRON-DONOR PROPERTIES OF DRINKING WATER].
AB  - In a study there was performed the experimental evaluation of long-term
      structural--physical changes of the phase of associated water in drinking water
      treated in hypomagnetic conditions according to the the technology providing the
      retention of of ortho/para isomers of water in the presence of a catalyst-
      triplet oxygen. According to the results of measurements ofparameters of nano
      associates formed in the water there was found a series ofconsistencies, allowing
      to determine the mechanisms of the impact of hypomagnetic treatment on the
      catalytic properties ofwater and long-term stability of its activated state, that
      provides the long-term maintenance of high biological activity of drinking water.
      In particular, under hypomagnetic conditions of the treatment there is formed
      denser packing of amorphous ice--VI in the composition of associates peroxide,
      serving as a kind of "reservoir" of atmospheric gases. In such a "reservoir"
      there realized higher pressure, compared with normal geophysical conditions, that
      stimulates the gas-phase reactions with the formation of dimers and trimers of
      oxygen existing in the 2-electron--active configurations with binding energies of
      0.3 eVand ~0.2 eV providing phase modulation, resulting in condensation of
      environment additional electrons on paramagnetic oxygen, which provides the long
      term maintenance of the electron--donor ability of water and electrically non
      equilibrium state.

PMID- 26302572
TI  - [DIRECTIONALITY OF THE BIOLOGICAL EFFECT OF DRINKING WATER].
AB  - There have been performed the studies of the dimensional parameters of peroxide
      associates in drinking water, per- forming regulatory functions in cellular
      metabolism, that determine the character of the biological response of the human
      body to drinking water The direction of action of peroxide associates type Sigma
      [(HO2-(*) ... OH-(*) (H2O) tp)]q, (where (H2O) tp is an associate with the
      tetragonal structure (Walrafen pentamer Is ice VI), q is the degree of
      association p--parameter of ion coordination) on the cellular structures of the
      organism is associated with their quantum properties, determining the macroscopic
      parameters of the electron wave packets. Research has confirmed the addressness
      of the nonlocal entering electron to certain cellular structures of the body,
      which is determined by the structural similarity of centers of condensation of
      electrons in the cells of systems and organs of the body with the parameters of
      the electron wave packets in the associates. Methodology for the estimation of
      the orientation of biological effect of the drinking water to the systems of the
      body on the base of the analysis of variations in heart rhythm under non-contact
      influence of water on the human body and its relationship with the dimensional
      parameters and peroxide activity of associates in drinking water can be suggested
      for the implementation of screening tests for drinking water quality, taking into
      account both the individualfeatures of responses of body systems to drinking
      water and its group action.

PMID- 26302573
TI  - [EVALUATION OF THE CYTOGENETIC AND MUTAGEN-MODIFYING ACTIVITY OF CAFFEINE IN
      MOUSE BONE MARROW CELLS].
AB  - The cytogenetic and mutagen-modifying activity of caffeine was studied with the
      method of chromosomal aberrations in bone marrow cells of mice hybrids F1
      CBAxC57BL/6. Caffeine per se was administered intragastrically or
      intraperitoneally, and in combination with mutagens--intragastrically. Mutagens
      injected intraperitoneally. Caffeine at doses of 10 and 100 mg/kg (single dose)
      and 10 mg/kg (five days) in parenteral administration and oral introduction
      failed to possess cytogenetic activity. In combination with mutagens caffeine (1,
      10 and 100 mg/kg) had no effect on the cytogenetic activity of dioxydine (200
      mg/kg/intraperitoneally) for a single coadministration, five-day pre or five-day
      coadministration. In combination with other mutagens under the same processing
      conditions caffeine at doses of 10 and 100 mg/kg significantly increased
      cytogenetic effects of cyclophosphamide (20 mg/kg) in the pretreatment of the
      animals and at the dose of 100 mg/kg significantly attenuated the cytogenetic
      effect of cisplatin (5 mg/kg) in single and repeated co-administration. Thus we
      have shown the absence of caffeine cytogenetic activity in vivo and showed the
      multidirectional effect of caffeine in doses far exceeding its daily consumption,
      to the manifestation ofcytogenetic effects of certain chemical mutagens in some
      modes of processing animals.

PMID- 26302574
TI  - [THE DEVELOPMENT AND VALIDATION OF THE GAS CHROMATOGRAPHY METHOD AND VALIDATION
      DEVELOPMENT FOR THE ORGANIC CYANIDE (CYANOETHYLENE) DETERMINATION IN EXPIRED
      AIR].
AB  - There are presented results of experimental studies on the development of gas
      chromatography method for the cyan ethylene determination in expired air During
      the process of the study there was chosen and proved the capillary gas
      chromatography method; there were investigated and elaborated optimal parameters
      of the gas chromatography separation of cyanoethylene with associated
      hydrocarbons together with the sample preparation and quantitative measurement
      methods. There was achieved the optimal level of gas chromatography
      quantification method for the cyan ethylene determination at 0, 00012 mg/m3, with
      the method uncertainty not more than 25%. The method was tried during the medical
      and biological examination of groups of 6-8 years old children, living in the
      territory of exposition from the moment of the birth and in the control
      territory.

PMID- 26302575
TI  - [ASSESSMENT OF PEFORMANCE IN STUDENTS WITH DIFFERENT TYPES OF THE NERVOUS SYSTEM
      WITH THE USE OF THE DEVELOPED SOFTWARE FOR PC "TAPPING-TEST"].
AB  - There was developed the PC software, which demonstrates the type of nervous
      system, allows us to differentiate people according to the empirical coefficient
      within groups with the same type of nervous system, provides information on the
      severity of the asymmetry of the hemispheres of the brain and shows the results
      of performance of the work It does not require additional calculations. With its
      use there were examined 1 and 2 courses students of the institution. Ehpyky was
      performed the comparative analysis of the progress of students with different
      types of nervous system. The academic performance in the examinees with a strong
      type of nervous system was significantly higher than in those with a weak type.
      In order to improve professional training the assessment of the type of the
      nervous system can be used in the educational process for the identification and
      correction of students with a weak nervous system.

PMID- 26302576
TI  - [METHODOLOGY FOR THE ASSESSMENT OF THE IMPACT OF THE ATMOSPHERIC AIR POLLUTION ON
      THE FORMATION OF THE LEVELS OF OVERALL MORBIDITY RATE OF BRONCHIAL ASTHMA].
AB  - In large cities with strong air pollution the formation of the levels of
      morbidity rate of bronchial asthma has a complex causation that requires the
      search for informative methods for identification of causes and consequences of
      this dependence. Method for the assessment of the dependence of overall levels of
      morbidity rate of bronchial asthma on the degree of air pollution allows you to
      select a "useful information" of the direct impact of air pollution on a
      background of random processes and latent relationship between human and
      environment. The use of the method of the information entropy analysis allowed us
      to estimate the total and the individual contribution of the separate components
      of air pollution on the formation of levels of total morbidity rate of bronchial
      asthma in the population of the city of Vladivostok. Levels of total incidence of
      this pathology were established to differ in various age groups. The adult
      population is more adapted to air pollution, but retains a high sensitivity to
      the impact of nitrogen dioxide. Levels of overall l morbidity rate of bronchial
      asthma in children and adolescents depend on the total air pollution with some
      dominance of the influence of suspended matter and carbon monoxide.

PMID- 26302577
TI  - [Sanitary maintenance of troops and civilians in the Great Patriotic War of 1941
      1945 (on the 70th anniversary of the Great Victory)].

PMID- 26302578
TI  - [Anniversary Dates in the History of Hygiene and Sanitation in 2015].

PMID- 26302579
TI  - [On the occasion of the 90th anniversary of the birth of K.I. Akulov].

PMID- 26302580
TI  - [On the occasion of the 105th anniversary of the birth of T.A. Nikolaeva].

PMID- 26302581
TI  - KICKING ASS. LONG-TERM SURVIVORS OF HIV/AIDS TAKE CONTROL OF THEIR DESTINY.

PMID- 26302582
TI  - ANAL CANCER: ARE YOU AT RISK? A PAP SMEAR THAT MANY MEN SHOULD GET, TOO.

PMID- 26302583
TI  - MARIA DAVIS SPEAKS OUT. A LONG-TERM SURVIVOR AND ACTIVIST OPENS UP ABOUT LIFE,
      LOVE, AND HIV-AND WHY WE NEED TO KEEP THE CONVERSATION GOING.

PMID- 26302585
TI  - AGING GRACIE-FULLY. FACING THE CHALLENGES OF GROWING OLDER WITH HIV AS A
      COMMUNITY.

PMID- 26302584
TI  - INTEGRATING PREVENTION STRATEGIES.

PMID- 26302586
TI  - THOUGHTS ON PrEP--FROM THE FIRST PERSON CURED OF HIV.

PMID- 26302587
TI  - Cracking the code 24:7.

PMID- 26302588
TI  - A gut feeling.

PMID- 26302589
TI  - The soothing patients' anxiety 'SPA' experience.
AB  - This paper examines a blended approach to minimising patient anxiety levels prior
      to general anaesthesia for adult and paediatric patients with a learning
      disability by introducing reasonable adjustments and reasonable distractions. A
      therapeutic environment is created that promotes wellbeing; restrictive
      interventions are used only when there is potential for harm to the patient or
      others. The result can be excellent holistic individual patient care, the patient
      receiving 'added value' and a positive experience.

PMID- 26302590
TI  - Pathophysiology and perioperative management of sickle cell disease.
AB  - Sickle cell disease has become the most common genetic condition in some European
      countries (Roberts & De Montalembert 2007).The disease is characterised by the
      painful sickle cell crisis often experienced by sufferers. This article sets out
      to examine the pathophysiology of this disease, alongside the factors that
      perioperative practitioners need to be aware of in order to reduce the risk of
      triggering a sickle cell crisis.

PMID- 26302591
TI  - A training programme for operating theatre personnel in transanal endoscopic
      operation procedures for local excision of rectal tumours.
AB  - The transanal endoscopic operation (TEO) is a minimal access surgical procedure
      for the removal of benign and early malignant rectal tumours (Nieuwenhuis et al
      2009). This surgery involves specialist equipment, set up and positioning by the
      perioperative team. We report on and evaluate the first ever TEO course designed
      specifically for theatre practitioners.

PMID- 26302592
TI  - Closing the audit cycle: improving short-term outcomes of oesophagectomy in a
      provincial hospital.
AB  - A previously published study regarding the outcomes of oesophagectomy at a
      provincial hospital identified issues with perioperative care (Al-Herz et al
      2012). The aim of this study was to evaluate the effect of changes in management
      at the institution concerned. This was a cohort study which compared the outcomes
      of 30 patients undergoing oesophagectomy before the unit audit and 30 patients
      after it. Demographics, operative details, recovery parameters, and oncological
      data were collected retrospectively. There was a significant reduction in the use
      of intravenous fluid, both intraoperatively (6.6 vs 3.3L, P < 0.0001) and during
      the first 24 hours (9.2 vs 5.5L, P < 0.0001). Patients were extubated three days
      earlier (P < 0.001) after the audit, and the percentage of patients requiring
      tracheostomy was smaller (26.7% vs 0%, P = 0.003). The length of total hospital
      stay was shorter (15 vs 13 days, P = 0.035). We conclude that the publication of
      a unit audit changed perioperative practice and resulted in a significant
      improvement in the short term outcomes after oesophagectomy.

PMID- 26302593
TI  - The first successful gastrectomy.
AB  - In the latter part of the 19th century safe and effective elective abdominal
      surgery seemed to be, at last, more than just a dream. This possibility followed
      two vital advances. First, the introduction of anaesthesia, heralded by the use
      of ether by William Morton in Boston in 1845 and then of chloroform by J.Y.
      Simpson in Edinburgh a couple of years later, and second the work of Joseph
      Lister on the antiseptic method of surgery, following his publication on this
      subject in the Lancet in 1867. (Interestingly enough, as far as I know, Lister
      himself never performed a laparotomy--if anything he was principally an
      orthopaedic surgeon.) The major elective abdominal problem facing the surgeon at
      that time was the surgical management of carcinoma of the stomach--then the
      commonest killing cancer.

PMID- 26302594
TI  - ANTIRETROVIRAL THERAPY IN 2015. ONE DOCTOR'S PERSPECTIVE ON THE STATE OF HIV
      TREATMENT.

PMID- 26302595
TI  - Getting the most out of your drug guide.

PMID- 26302596
TI  - WHAT'S ON THE HORIZON. A LOOK AT NEW DRUGS IN DEVELOPMENT.

PMID- 26302597
TI  - THE HIGH COST OF LIVING. ACCESSING EXPENSIVE MEDICATIONS IS AN ART.

PMID- 26302598
TI  - Remarks of the FDA Commissioner: The Food and Drug Law Institute's 58th Annual
      Conference.

PMID- 26302599
TI  - A New Wave of Vaccines for Non-Communicable Diseases: What Are the Regulatory
      Challenges?
AB  - Vaccines represent one of the greatest achievements of medicine, dramatically
      reducing the incidence of serious or life-threatening infectious diseases and
      allowing people to live longer, healthier lives. As life expectancy has
      increased, however, the burden of non-communicable diseases (NCDs) such as
      cancer, hypertension, atherosclerosis, and diabetes has increased. This shifting
      burden of disease has heightened the already urgent need for therapies that treat
      or prevent NCDs, a need that is now being met with increased efforts to develop
      NCD vaccines. Like traditional vaccines, NCD vaccines work by modulating the
      human immune system, but target cells, proteins or other molecules that are
      associated with the NCD in question rather than pathogens or pathogen-infected
      cells. Efforts are underway to develop NCD vaccines to address not only cancer
      and hypertension, but also addiction, obesity, asthma, arthritis, psoriasis,
      multiple sclerosis, and Crohn's disease, among others. NCD vaccines present an
      interesting challenge for the U.S. Food and Drug Administration (FDA), which is
      tasked with approving new treatments on the basis of efficacy and safety. Should
      NCD vaccines be evaluated under the same analytic frame as traditional vaccines,
      or that of biologic drugs? Despite the borrowed nomenclature, NCD vaccines differ
      in important ways from infectious disease vaccines. Because infectious disease
      vaccines are generally administered to healthy individuals, often children,
      tolerance for adverse events is low and willingness to pay is limited. It is
      important to have infectious disease vaccines even for rare or eradicated disease
      (e.g., smallpox), in the event of an outbreak. The efficacy of infectious disease
      vaccines is generally high, and the vaccines convey population level benefits
      associated with herd immunity and potential eradication. The combination of
      substantial population-level benefits, low willingness to pay, and low tolerance
      for adverse events explains the need for the federal National Childhood Vaccine
      Injury Compensation Act, which encourages production and uptake by providing
      immunity from liability to industry and compensation to injured patients. These
      characteristics and considerations contrast sharply with those of NCD vaccines,
      raising the question of whether the term "vaccine" is appropriate for this new
      category of drugs. The article explores the emerging class of NCD vaccines,
      explains how they differ from traditional vaccines, and describes some regulatory
      implications of this innovative type of therapeutic.

PMID- 26302600
TI  - The Limits of FDA's Authority to Regulate Clinical Research Involving High
      Throughput DNA Sequencing.
AB  - The United States Food and Drug Administration (FDA) recently signaled its
      interest in subjecting clinical investigations that employ high-throughput gene
      sequencing, also called next-generation sequencing, to the agency's Part 812
      investigational device exemption (IDE) regulation. Genome sequencing--for reasons
      explained in this article--blurs the line between categories of in vitro
      diagnostic (IVD) research that FDA traditionally has regulated and categories of
      research that FDA traditionally has not regulated. This blurring creates a risk
      that FDA may overstep its proper authority to regulate fundamental genomic and
      medical research. This article surveys the legal limits of FDA's authority'to
      subject genomic research to its IDE requirements. Section 1 explains that FDA has
      authority to regulate clinical investigations of devices, but is not authorized
      to regulate investigations that merely use devices to expand medical knowledge or
      to conduct fundamental research, unless special circumstances apply. Section 2
      discusses the special circumstances that can expand or limit FDA's authority to
      regulate a specific clinical investigation, and Section 3 demonstrates these
      using an example. Section 4 explores concerns that arose in recent years about
      risks to human subjects in a certain type of investigation known as sponsor
      investigator studies. In response to these concerns, FDA has suggested that it
      can regulate such studies in ways that threaten to expand FDA's regulation of
      research at academic medical centers beyond its proper scope. These concerns,
      while valid in some academic research contexts, seem inapposite in the setting of
      genomic research programs funded by responsible.entities such as the National
      Institutes of Health (NIH). Moreover, FDA's regulations do not. appear to support
      the proposition that FDA can regulate sponsor-investigator studies more
      expansively than it regulates other studies. Section 5 explores specific ways
      that NIH, clinical investigators, and FDA might work together to rationalize
      FDA's regulation of NIH-funded-genomic research.

PMID- 26302601
TI  - An Unfulfilled Promise: Changes Needed to the Drug Approval Process to Make
      Personalized Medicine a Reality.
AB  - The widespread availability of drugs for personalized medicine has been an
      aspiration since before the human genome was sequenced. Recently, there is
      renewed interest; personalized medicine is much in the news. Legislation has been
      considered with the goal of smoothing, shortening and incentivizing the approval
      process for therapeutic products. President Obama mentioned the need for new
      initiatives to achieve such goals in the State of the Union address. But most of
      these initiatives do not consider the fundamental changes that personalized
      medicine demands. It requires a statutory structure designed for the development
      of products applicable for small subpopulations that is very different from our
      current model which is designed for the development of products for large
      populations. The current approval process is purposely not designed to consider
      individual efficacy. It is designed to incentivize reduced variation in clinical
      trials rather than embracing variation. In addition, it is based on twentieth
      century notions of disease focused on phenotype rather than on pathophysiologic
      pathways. Current foci on the development of companion diagnostics, orphan drugs
      and post-approval study are important but insufficient. FDA does not have the
      authority to require the type of standardization, clinical trial design and
      extensive data reporting and sharing that. is needed to achieve the goals for
      personalized medicine. In addition, FDA's current drug approval process is too
      lengthy and cumbersome to deal with the iterative responses personalized medicine
      entails. If we are serious about wanting to achieve these goals, we will need to
      entertain such fundamental changes in authority.

PMID- 26302602
TI  - Revising the Regulation of Stem Cell-Based Therapies: Critical Assessment of
      Potential Models.
AB  - The regulation of stem cell-based therapies is challenging in many respects,
      given their unique safety, efficacy, and quality issues. At the same time, public
      interest in these innovative therapies has led some to question FDA's regulation
      of them, while others urge strict regulation and stronger enforcement. Within the
      context of this broader debate, this article examines recent attempts in other
      jurisdictions to craft specific provisions allowing additional flexibility in
      regulating cell and tissue therapies: Australia's exemption for autologous cell
      and tissue therapies, and the hospital exemption in Europe's regulation for
      advanced therapies.

PMID- 26302603
TI  - Synthetic Biology in the FDA Realm: Toward Productive Oversight Assessment.
AB  - Synthetic biology (SB) is expected to create tremendous opportunities in a wide
      range of areas, including in foods, therapeutics, and diagnostics subject to
      regulatory oversight by the United States Food and Drug Administration. At the
      same time, there is substantial basis for concern about the uncertainties of
      accurately assessing the human health and environmental risks of such SB
      products. As such, SB is the latest in a string of emerging technologies that is
      the subject of calls for new approaches to regulation and oversight that involve
      "thinking ahead" to anticipate governance challenges upstream of technological
      development and adopting oversight mechanisms that are both adaptive to new
      information about risks and reflexive to performance data and feedback on policy
      outcomes over time. These new approaches constitute a marked departure from the
      status quo, and their development and implementation will require considerable
      time, resources, and reallocation of responsibilities. Furthermore, in order to
      develop an appropriate oversight response, adaptive or otherwise, there is first
      a need to identify the specific types and natures of applications, uncertainties,
      and regulatory issues that are likely to pose oversight challenges. This article
      presents our vision for a Productive Oversight Assessment (POA) approach in which
      the abilities and deficits of an oversight system are evaluated with the aim of
      enabling productive decisions (i.e., timely, feasible, effective for achieving
      desired policy outcomes) about oversight while also building capacity to
      facilitate broader governance efforts. The value ofPOA is two-fold. First, it
      will advance the development of a generalizable approach for making productive
      planning and decision-making about the oversight of any given new technology that
      presents challenges and uncertainties for any given oversight system whose policy
      goals are implicated by that technology. Second, this effort can enhance the very
      processes advocated under anticipatory and adaptive approaches by laying the
      groundwork for and providing valuable data to support future normative
      deliberations about the governance of emerging technologies.

PMID- 26302604
TI  - START NOW. A NEW STUDY CONFIRMS THAT EVERYONE WHO IS HIV-POSITIVE SHOULD BE ON
      TREATMENT.

PMID- 26302605
TI  - Cool new tech may yet deliver value-based models.

PMID- 26302606
TI  - Decision support at work. Information technology helps to drive workflow
      improvement.

PMID- 26302607
TI  - Coding countdown continues. ICD-10 strategies, tactics must ramp up for October
      launch.

PMID- 26302608
TI  - The era of accountable care. Industry experts weigh-in on the status of ACOs.
AB  - The guiding principle behind accountable care organizations (ACOs) is a simple
      one: Coordinate health services to maximize efficiency and facilitate better
      patient outcomes. Providers would be paid for the results they produce, not
      simply for the care they provide. Over the years, these coordinating groups of
      practices have gone by many names, but it wasn't until the reforms of the
      Affordable Care Act that ACOs began to take their present form, focusing on
      meeting new patient satisfaction benchmarks and reducing the financial burden
      caused by patients receiving unnecessary services. While the hype for ACOs
      promised better care quality and increased revenue, the reality of ACO launches
      has seen mixed results. Health Management Technology asks two industry experts
      for their views on the present and future of the accountable care model, now that
      ACOs have become a reality.

PMID- 26302609
TI  - Protecting health data in a troubling time. Understand who and what you're up
      against.

PMID- 26302610
TI  - Ensuring EHR compliance for Meaningful Use.

PMID- 26302611
TI  - Where compliance meets opportunity.

PMID- 26302612
TI  - Document imaging helps providers digitize patient records. Scanning makes meeting
      Meaningful Use objectives easier.

PMID- 26302613
TI  - With patient portals, doctors win too.

PMID- 26302614
TI  - Customizing care.

PMID- 26302615
TI  - Finding the path toward fee-for-value.

PMID- 26302616
TI  - [Orbital radiographic anatomy. Part 1. The osseous orbit and its apex].
AB  - OBJECTIVE: To study the characteristics of the osseous orbit and its apex in
      health. MATERIAL AND METHODS: The computed tomography scans of 210 individuals
      (266 orbits) without orbital disease were examined. RESULTS: The paper presents
      linear indicators (horizontal input, vertical input, length) of the osseous orbit
      and its apex in health. It is emphasized that the volume of the osseous orbit and
      its apex in healthy men and women has statistically significant differences.
      Individual asymmetry of osseous orbital volumes in health was detected in 80.95%
      of the men and in 82.85% of the women; asymmetry of orbital fat volume was in
      47.61% of the men and in 51.42% of the women. CONCLUSION: The asymmetry of the
      mean normal osseous orbital volumes in the population is only within the margin
      of statistical error. At the same time the individual asymmetry of osseous
      orbital volumes in health is as much as 3.0 cm3; that of osseous orbital apical
      volumes is not greater than 1.0 cm3. The linear and volume characteristics of the
      osseous orbit and its apex are useful in estimating the degree of clinical
      symptoms. These should be kept in mind in the differential diagnosis of true and
      false exophthalmos and these can also play a crucial role in choosing surgical
      tactics.

PMID- 26302618
TI  - [Is suprastenotic dilatation a mandatory symptom of impaired bile outflow?].
AB  - OBJECTIVE: To study the rate, nature, and symptoms of bile flow impairments
      running without developing suprastenotic dilatation. MATERIAL AND METHODS: A
      total of 1082 patients undergoing endoscopic retrograde cholangiopancreatography
      for the differential diagnosis of jaundices were followed up. According to the
      diameter of the common bile duct, the patients were classified into
      cholangioectasia and non-cholangioectasia groups. The investigators studied the
      causes of bile evacuation disorders; the levels of bilirubin, hepatic
      transferases, and alkaline phosphatase; the duration and periodicity of
      obstructive jaundice; extended compression of suprastenotic dilatation; the
      occurrence of other symptoms; and the efficiency of additional procedures for the
      differential diagnosis of hepatic and obstructive jaundices. RESULTS: There was
      no suprastenotic dilatation in 11 cases: in noncircular amorphous internal
      hepatocholedochal blocks, in cicatrical stenoses of the hepatocholedoch, in
      excessive metastatic spread into the hepatic portal and parenchyma, extended
      stenosis of the common bile duct does not lead to intrahepatic cholangiectasia.
      In 9 cases, instrumental palpation and aspiration biopsy were used to visualize
      common bile duct stenosis in order to elucidate its nature, degree, and rigidity.
      Endobiliary stenting was employed for the differential diagnosis of jaundices.
      CONCLUSION: No suprastenotic dilatation was seen in 0.8% of patients with organic
      bile flow impairment. In these cases, obstacles to bile flow may be suggested by
      clear-cut variations in the diameter of the hepaticocholedoch and its deformity.
      The absence of suprastenotic dilatation may be partly explained by excessive
      metastatic liver involvement and malignant hepatoduodenal ligament infiltration.
      When suprastenotic dilatation is absent, instrumental palpation and diagnostic
      and therapeutic stenting may be used for the differential diagnosis of
      obstructive and hepatic jaundices.

PMID- 26302617
TI  - [Multislice computed tomography in the diagnosis of orbital fractures].
AB  - OBJECTIVE: To improve radiodiagnosis of orbital fractures at pre- and
      postoperative treatment stages, to provide a rationale for detailed evaluation of
      orbital osseous and soft tissue structures to prevent early postoperative
      complications. MATERIAL AND METHODS: The I.M. Sechenov First Moscow State Medical
      University Clinic examined 52 (100%) patients on days 1-2 after injury. A patient
      group consisted of 49 (94%) men and 3 (6%) women whose age was 17 to 49 years.
      Multislice computed tomography (MSCT) was carried out prior to surgery on the day
      of their admission. Postoperative MSCT was done within 7-10 days after surgical
      treatment. RESULTS: Preoperative MSCT could reveal fractures of the inferior and
      lateral orbital walls in all 52 (100%) patients. Fractures of the medial and
      superior orbital walls were identified in 8 (15%) and 3 (6%) cases, respectively.
      In 12 (23%) patients, prolapse of the fat and oculomotor muscles into the
      respective maxillary sinus was imaged, which gave rise to enophthalmos and an
      increase in orbital volume. Three (6%) patients were identified as having sequels
      of eyeball trauma. Optic nerve abnormality was detected in 11 (21%) patients.
      Oculomotor muscle injury was encountered in 20 (38%) patients. After surgical
      treatment, 4 (8%) patients had a persistent inferior orbital wall defect in the
      posterior portions where the retrobulbar fat prolapsed into the maxillary sinus.
      Three (6%) out of the 20 (38%) patients with different oculomotor abnormalities
      had persistent postoperative muscle injuries that were mainly associated with
      erroneous orbital floor implantation. The number of patients with eyeball disease
      remained unchanged--3 (6%). Among 11 (21%) patients with a postoperative
      pathologically changed tortuous nerve course, the optic nerve attained its
      correct even course all the way in 5 (10%) cases; it remained pathologically
      changed as before in 6 (12%) cases. CONCLUSION: MSCT is the preoperative
      technique of choice for examining patients with orbital injuries. After surgery,
      MSCT in the early postoperative period makes it possible to assess the results of
      treatment and to reveal possible complications and it is a decisive guide for a
      doctor in charge when planning resurgery.

PMID- 26302619
TI  - [Radiographic morphometry of intervertebral spaces of the vertebral column in
      health and dystrophic changes in the intervertebral disks].
AB  - OBJECTIVE: To develop a radiographic morphometric procedure for estimating the
      sizes and shapes of intervertebral spaces in the thoracic and lumbar spine and to
      evaluate the status of intervertebral spaces in women in health in terms of their
      age and in dystrophic transformations of intervertebral disks. MATERIAL AND
      METHODS: The data of a radiographic morphometric study of the sizes and forms of
      intervertebral spaces were analyzed in 127 women of different ages. Lateral
      thoracic and lumbar spondylograms performed in compliance with a number of
      requirements were used to estimate the sizes of anterior, middle, and posterior
      portions of intervertebral spaces (from T4 to L5); the magnitude of dystrophic
      changes in the intervertebral disks were determined applying semiquantitative
      methods. RESULTS: The intervertebral space width of the lower segment was more
      than that of the upper one. The differences in the width of intervertebral spaces
      of the neighboring segments in the lower portions of the vertebral column were
      greater than those in its upper portions. The intervertebral spaces (T4-T12) were
      biconvex in shape and those in the upper lumbar segments were posterior wedge
      shaped. There was no noticeable narrowing of the intervertebral spaces with age.
      The age group of 70 years or older showed a significant moderate increase in the
      height of intervertebral spaces in the middle and lower thoracic vertebral
      segments. In varying degrees of dystrophic intervertebral disc changes, their
      most pronounced manifestations were found to be accompanied by a decrease in the
      width of intervertebral spaces in the lower half of the vertebral column in
      conjunction with their normal shape being impaired. CONCLUSION: The sizes and
      shape of intervertebral spaces show a number of regularities associated with the
      position of a segment in the vertebral column. In the bulk of the thoracic spine,
      the vertebral spaces are biconvex in shape and those in the transient
      thoracolumbar area and in the lumbar segment were posterior wedge-shaped. The age
      related changes in the sizes and shape of intervertebral spaces are associated
      with their slight dilatation at the age of 70 years or older, without their
      normal shape being impaired. When dystro- phic intervertebral disk changes
      develop, there is a moderate narrowing of intervertebral spaces in the lower half
      of the vertebral column in conjunction with a wedge-like alteration in
      intervertebral discs, their shape.

PMID- 26302620
TI  - [Lieutaud's triangle lesion and urodynamic disorders in bladder cancer according
      to magnetic resonance imaging data].
AB  - OBJECTIVE: To estimate the capabilities of magnetic resonance imaging (MRI) in
      revealing bladder tumor in relation to its sizes and location and in diagnosing
      concomitant urodynamic disorders. MATERIAL AND METHODS: A total of 93 patients
      (78 men and 15 women; mean age, 62.1 +/- 12.2 years) with bladder cancer were
      examined. Examinations were made using 1.5 T MRI according to an extended
      protocol with a mandatory inclusion of diffusion-weighted images; dynamic
      contrast-enhanced MRI was carried out in 86 patients. RESULTS: There were single
      nodules in 48.7% of the patients and multiple bladder wall lesions in 51.3%.
      Bladder wall injury involving the functional area of Lieutaud's triangle was
      revealed in 67.5% of the patients. Single and multiple tumors in Lieutaud'
      triangle were observed in 58.9 and 80.5% of cases. Ureteral orifice involvement
      led to secondary ureterectasia in 68.2%. CONCLUSION: As the number of tumors
      detected in the bladder increases, the risk of tumors in Lieutaud's triangle
      injury rises. The involvement of the triangle into the pathological process is
      accompanied by impaired urodynamics as uretere- ctasia in every four cases
      (26.8%; p < 0.008). It is shown that dynamic contrast-enhanced MRI must
      necessarily be performed to better visualize a tumor and to determine its
      relationships to the underlying wall and basic structures of the bladder.

PMID- 26302621
TI  - [Magnetic resonance imaging in the diagnosis of secondary vaginal tumor
      involvement].
AB  - OBJECTIVE: To estimate the capabilities of magnetic resonance imaging (MRI) in
      revealing and estimating the extent of secondary vaginal involvement. MATERIAL
      AND METHODS. Thirty patients with secondary vaginal tumor involvement underwent
      contrast-enhanced MRI. Examinations were made using a 1.5 T MRI. The protocol
      encompassed T2- and T1-weighted, diffusion-weighted, and dynamic contrast
      enhanced MRIs. To smooth out vaginal wall rigosity, the examination was made
      using an intracavitary MR-compatible applicator. RESULTS: Vaginal metastatic
      involvement was detected in 30 patients with sustained malignancies at various
      sites. The largest group consisted of 16 (53.3%) patients with uterine corpus
      metastases. Secondary vaginal involvement was observed in 11(36.7%) patients with
      cervix uteri cancer, in 2 (6.7%) patients with progressive ovarian cancer, and in
      1 (3.3%) patients with rectal cancer. With a significant tumor volume giving rise
      to thickening of the vaginal wall or its impaired slice differentiation, the
      portion of an inhomogeneously increased MR signal portion during T2-weighted MRI,
      which intensively accumulated the paramagnetic in an arterial and venous phase of
      dynamic contrast-enhanced MRI, was detected. There were no T2-weighted images of
      a hypointense muscular layer and paravaginal fat streaks during an invasive
      process. In our investigation, vaginal metastatic tumors which were enclosed by
      the mucous membrane and evident as shallow erosion, as shown by the data of
      clinical and histological examinations, had no specific MRI signs in any of the
      pulse patterns, which is likely to be associated with the resolution of this
      technique. CONCLUSION: The proposed protocol of comprehensive magnetic reso nance
      imaging makes it possible to clearly localize a tumor process into the vagina and
      to determine the volume and pattern of involvement in most patients, including
      whose who have a history of antitumor treatment.

PMID- 26302622
TI  - [Pulmonary cytotoxicity induced by bleomycin and methotrexate].
AB  - Early detection of drug-induced pulmonary parenchymal injuries is often hampered
      by nonspecific clinical and X-ray manifestations. The diagnosis is usually based
      on a history of drug use, clinical and X-ray presentation, and exclusion of other
      causes of lung tissue injury. Chemical preparations most commonly cause
      pathological pulmonary changes. Overall, about 10% of all patients receiving
      chemotherapy develop pathological changes in the lung parenchyma. The main
      chemical preparations causing lung injury are bleomycin, methotrexate,
      carmustine, busulfan, and cyclophosphamide. Out of all examination techniques,
      computed tomography is most sensitive in determining the presence, specific
      features, and trends in the development of drug-induced pulmonary parenchymal
      disease. The paper gives the data available in the literature and 2 clinical
      observations of pulmonary parenchymal disease induced by bleomycin and
      methotrexate.

PMID- 26302623
TI  - [Current minimally invasive procedures for the verification of diagnosis in
      patients with lung tumors].
AB  - Lung cancer is one of the problems of modern oncology, which remains relevant.
      Its morphological verification is the key moment to choose chemotherapy. Based on
      the extent of a tumor process, surgery is not indicated in the majority of cases,
      which necessitates that materials should be obtained preoperatively and when
      surgery is not indicated to choose effective chemotherapy.

PMID- 26302624
TI  - The tragedy of the electronic health record.

PMID- 26302625
TI  - SURVIVING HURRICANE KATRINA.

PMID- 26302626
TI  - Andrew Wyeth, Christna Olson, and the art of medicine.

PMID- 26302627
TI  - In the hollow of her world. Healing and the defiance of illness in Christina's
      World.

PMID- 26302628
TI  - Happy tears.

PMID- 26302629
TI  - Re "The Electronic Health Record".

PMID- 26302630
TI  - A new vision for RN practice.

PMID- 26302631
TI  - Collaboration in caring. A new approach to health care.

PMID- 26302632
TI  - Palliation. A new beginning for end of life care.

PMID- 26302634
TI  - STAGE COACH.

PMID- 26302633
TI  - The future of expert care.

PMID- 26302636
TI  - AFTER THE MCI.

PMID- 26302635
TI  - PAGE'S LEGACY.

PMID- 26302637
TI  - OUT WITH THE OLD.

PMID- 26302638
TI  - EPILEPTIC EFFECT.

PMID- 26302639
TI  - ABSENT ASPIRIN.

PMID- 26302640
TI  - TRIAGE PERSPECTIVES.

PMID- 26302641
TI  - ADAPT TO DEMAND.

PMID- 26302642
TI  - 48-DAY MANHUNT.

PMID- 26302643
TI  - Airport crash.

PMID- 26302644
TI  - THERE IN A FLASH.

PMID- 26302645
TI  - FOCUS ON QUALITY.

PMID- 26302646
TI  - EBOLA VIRUS DISEASE.

PMID- 26302647
TI  - COLLABORATIVE DATA.

PMID- 26302648
TI  - Measuring compassion in nurses and other healthcare professionals: An integrative
      review.
AB  - BACKGROUND: Compassion is an essential part of nursing practice. However recent
      high profile public inquiries have uncovered failings in the NHS and revealed a
      need for nursing education to assure that both undergraduate and postgraduate
      healthcare professionals receive training in compassion. OBJECTIVES: The aim of
      this study was to review how compassion is being measured in nurses and other
      healthcare professionals. REVIEW METHODS: An integrative review methodology was
      used. The literature was searched systematically, using electronic databases,
      internet searches, recommendations by experts in the field, and manual searches.
      RESULTS: Six papers on measuring compassion in healthcare were included in the
      final analysis. Several overarching themes were identified as the main elements
      of compassion being measured. These included: being empathetic, recognising and
      ending suffering, being caring, communicating with patients, connecting to and
      relating with patients, being competent, attending to patients needs/going the
      extra mile, and involving the patient. CONCLUSIONS: Further research is needed to
      develop and test tools that nurse and healthcare educators can use to assess the
      levels of compassion in their undergraduate and postgraduate students, as well as
      making this available to qualified nurses in practice.

PMID- 26302649
TI  - Developing a multi-method approach to data collection and analysis for explaining
      the learning during simulation in undergraduate nurse education.
AB  - Simulation has become an established feature of undergraduate nurse education and
      as such requires extensive investigation. Research limited to pre-constructed
      categories imposed by some questionnaire and interview methods may only provide
      partial understanding. This is problematic in understanding the mechanisms of
      learning in simulation-based education as contemporary distributed theories of
      learning posit that learning can be understood as the interaction of individual
      identity with context. This paper details a method of data collection and
      analysis that captures interaction of individuals within the simulation
      experience which can be analysed through multiple lenses, including context and
      through the lens of both researcher and learner. The study utilised a grounded
      theory approach involving 31 under-graduate third year student nurses. Data was
      collected and analysed through non-participant observation, digital recordings of
      simulation activity and focus group deconstruction of their recorded simulation
      by the participants and researcher. Focus group interviews enabled further
      clarification. The method revealed multiple levels of dynamic data, concluding
      that in order to better understand how students learn in social and active
      learning strategies, dynamic data is required enabling researchers and
      participants to unpack what is happening as it unfolds in action. 

PMID- 26302650
TI  - Lower respiratory tract disorder hospitalizations among children born  via
      elective early-term delivery.
AB  - OBJECTIVE: We evaluated the hypothesis that elective early-term delivery
      increases the risk of childhood lower respiratory tract disorder hospitalization.
      METHODS: Children born via early-term elective inductions were compared to full-
      or late-term elective inductions in a retrospective cohort study using Washington
      State birth certificate and hospital discharge data. Outcomes were the odds of
      lower respiratory disorder hospitalization before age five and cause specific
      odds ratios for asthma, bronchiolitis, bronchitis, and pneumonia. In addition, a
      subgroup analysis excluding infants with perinatal complications was conducted.
      RESULTS: Electively induced early-term children were at significantly increased
      risk of hospitalization before age five for lower respiratory disorders compared
      to similar full- or late-term children (adjusted OR: 1.31, 95% CI: 1.11-1.55).
      Bronchiolitis was the only cause-specific outcome with a statistically
      significant increase in odds of hospitalization, though comparable increases were
      found for the less common diagnoses of asthma (adjusted OR: 1.39, 95% CI: 0.93
      2.08) and pneumonia (adjusted OR: 1.27, 95% CI: 0.99-1.64). Excluding infants
      with perinatal complications did not alter the results. CONCLUSIONS: There was an
      association between electively induced early-term delivery and hospitalization
      for lower respiratory tract disorders before age five. This reinforces policies
      discouraging elective early-term delivery.

PMID- 26302651
TI  - Japanese cedar pollen-based subcutaneous immunotherapy decreases tomato fruit
      specific basophil activation.
AB  - BACKGROUND: Some patients with Japanese cedar pollen (JCP)-induced allergic
      rhinitis develop pollen-food allergy syndrome (PFAS) as a reaction to tomato
      fruit. Pollen allergen-specific subcutaneous immunotherapy (SCIT) is reportedly
      beneficial for some associated food allergies; however, the reported changes in
      food allergen-specific immunoglobulin (Ig)E and IgG4 levels are inconsistent.
      Here, we investigated immunologic reactivity to tomato fruit after JCP-based
      SCIT. METHODS: Twenty-three children (aged 6-17 years) with JCP-induced allergic
      rhinitis and sensitized to tomato (serum tomato fruit-specific IgE level >0.34
      UA/ml) received JCP-based SCIT. Basophil activation by tomato and JCP extracts
      and serum-specific IgE and IgG4 levels against these allergens were determined
      before and after 4 or 5 months of maintenance SCIT. Basophil activation was
      assessed by monitoring CD203c upregulation on flow cytometry. RESULTS: JCP-based
      SCIT significantly reduced the basophil activation caused by tomato fruit (p =
      0.03) and JCP (p < 0.001) extracts. JCP-specific IgG4 levels markedly increased
      after SCIT (p < 0.001), whereas tomato fruit-specific IgG4 levels did not. After
      SCIT, no significant changes were observed in specific IgE levels for tomato
      fruit (p = 0.11) or JCP (p = 0.19). CONCLUSIONS: Tomato fruit-specific basophil
      activation decreases after JCP-based SCIT, suggesting that it is efficacious in
      relieving and preventing the symptoms of PFAS in patients with JCP-induced
      allergic rhinitis.

PMID- 26302652
TI  - The bed nucleus of the stria terminalis regulates ethanol-seeking behavior in
      mice.
AB  - Drug-associated stimuli are considered important factors in relapse to drug use.
      In the absence of drug, these cues can trigger drug craving and drive subsequent
      drug seeking. One structure that has been implicated in this process is the bed
      nucleus of the stria terminalis (BNST), a chief component of the extended
      amygdala. Previous studies have established a role for the BNST in cue-induced
      cocaine seeking. However, it is unclear if the BNST underlies cue-induced seeking
      of other abused drugs such as ethanol. In the present set of experiments, BNST
      involvement in ethanol-seeking behavior was assessed in male DBA/2J mice using
      the conditioned place preference procedure (CPP). The BNST was inhibited during
      CPP expression using electrolytic lesions (Experiment 1), co-infusion of GABAA
      and GABAB receptor agonists muscimol and baclofen (M+B; Experiment 2), and
      activation of inhibitory designer receptors exclusively activated by designer
      drugs (hM4Di-DREADD) with clozapine-N-oxide (CNO; Experiment 3). The magnitude of
      ethanol CPP was reduced significantly by each of these techniques. Notably,
      infusion of M+B (Exp. 2) abolished CPP altogether. Follow-up studies to Exp. 3
      showed that ethanol cue-induced c-Fos immunoreactivity in the BNST was reduced by
      hM4Di activation (Experiment 4) and in the absence of hM4Di, CNO did not affect
      ethanol CPP (Experiment 5). Combined, these findings demonstrate that the BNST is
      involved in the modulation of cue-induced ethanol-seeking behavior.

PMID- 26302653
TI  - Noribogaine is a G-protein biased kappa-opioid receptor agonist.
AB  - Noribogaine is the long-lived human metabolite of the anti-addictive substance
      ibogaine. Noribogaine efficaciously reaches the brain with concentrations up to
      20 MUM after acute therapeutic dose of 40 mg/kg ibogaine in animals. Noribogaine
      displays atypical opioid-like components in vivo, anti-addictive effects and
      potent modulatory properties of the tolerance to opiates for which the mode of
      action remained uncharacterized thus far. Our binding experiments and
      computational simulations indicate that noribogaine may bind to the orthosteric
      morphinan binding site of the opioid receptors. Functional activities of
      noribogaine at G-protein and non G-protein pathways of the mu and kappa opioid
      receptors were characterized. Noribogaine was a weak mu antagonist with a
      functional inhibition constants (Ke) of 20 MUM at the G-protein and beta-arrestin
      signaling pathways. Conversely, noribogaine was a G-protein biased kappa agonist
      75% as efficacious as dynorphin A at stimulating GDP-GTP exchange (EC50=9 MUM)
      but only 12% as efficacious at recruiting beta-arrestin, which could contribute
      to the lack of dysphoric effects of noribogaine. In turn, noribogaine
      functionally inhibited dynorphin-induced kappa beta-arrestin recruitment and was
      more potent than its G-protein agonistic activity with an IC50 of 1 MUM. This
      biased agonist/antagonist pharmacology is unique to noribogaine in comparison to
      various other ligands including ibogaine, 18-MC, nalmefene, and 6'-GNTI. We
      predict noribogaine to promote certain analgesic effects as well as anti
      addictive effects at effective concentrations>1 MUM in the brain. Because
      elevated levels of dynorphins are commonly observed and correlated with anxiety,
      dysphoric effects, and decreased dopaminergic tone, a therapeutically relevant
      functional inhibition bias to endogenously released dynorphins by noribogaine
      might be worthy of consideration for treating anxiety and substance related
      disorders.

PMID- 26302654
TI  - Intravenous self-administration of entactogen-class stimulants in male rats.
AB  - The intravenous self-administration (IVSA) of 3,4-methylenedioxymethamphetamine
      (MDMA) is inconsistent in rats, with up to half of subjects failing to acquire
      reliable drug intake. It is unknown if this changes under long-access conditions
      (6 h sessions) under which the IVSA of cocaine and methamphetamine escalates. The
      entactogen class cathinone stimulants which exhibit MDMA-like monoamine effects
      in the nucleus accumbens, mephedrone (4-methylmethcathinone) and methylone (3,4
      methylenedioxymethcathinone), may support more reliable IVSA but results have
      been mixed. This study was designed to directly compare the IVSA of these three
      compounds. Groups of male Wistar rats were trained to self-administer mephedrone,
      methylone or MDMA (0.5 mg/kg/inf) under a Fixed-Ratio (FR) 1 schedule of
      reinforcement for 14 sessions. Following the acquisition interval, animals were
      evaluated in FR (0.0, 0.125, 0.25, 0.5, 1.0, 2.5 mg/kg/inf) and Progressive Ratio
      (PR; 0.125, 1.0 mg/kg/inf) dose-substitution procedures. Long access conditions
      escalated MDMA intake over the 6 h session but not in the first 2 h. In short
      access, drug intake was significantly higher in mephedrone-trained rats compared
      with either the methylone-trained or MDMA-trained groups during acquisition.
      Mephedrone resulted in the highest intakes during FR and PR dose-substitution in
      MDMA- and mephedrone-trained groups. Overall it was found that mephedrone is a
      more effective reinforcer than methylone or MDMA and represents a higher risk for
      compulsive use. 

PMID- 26302656
TI  - Personality and professional commitment of students in nursing, social work, and
      teaching: A comparative survey.
AB  - BACKGROUND: Nurses are often portrayed as possessing specific traits and
      dispositions associated with care and empathy. The assumption has been that
      possessing these traits makes nurses competent, engaged, and well suited to their
      job. This proposition has been mostly normative, and few studies have
      investigated how this plays out empirically. OBJECTIVE: The aims of this study
      were to investigate (a) whether possessing a personality trait related to empathy
      and care was more common among nursing students than students in teaching and
      social work programs and (b) whether nursing students possessing an affirming
      personality trait judged themselves to be more suited to their future work -
      understood as commitment to the profession - than students in teaching and social
      work. DESIGN: A cross-sectional survey design was used. PARTICIPANTS AND SETTING:
      All first-year students attending seven Norwegian universities and university
      colleges were invited to participate in the study. Of the 1675 students who
      participated in the survey, 527 were nursing students, 668 were students in
      teaching, and 480 were social work students. A response rate of 65 percent was
      achieved. METHODS: The survey was conducted by Oslo and Akershus University
      College in the autumn of 2012. Data collection methods included both a paper-and
      pencil questionnaire and an online survey. Instruments used included Blau's
      Career Commitment Scale and Orlinsky and Ronnestad's Interpersonal Adjective
      Scale. Analysis of variance and regression analysis were performed on the data.
      RESULTS: Nursing students did not differ from students in teaching and social
      work programs in terms of the degree of affirming personality trait. Furthermore,
      the regression analysis revealed an equally strong association between having an
      affirming personality trait and being committed to the profession among all these
      student groups. CONCLUSION: The results of this study indicate that the narrative
      of nursing students as individuals who possess a special personality
      characteristic does not entirely reflect reality.

PMID- 26302655
TI  - Glycine transporter 1 is a target for the treatment of epilepsy.
AB  - Glycine is the major inhibitory neurotransmitter in brainstem and spinal cord,
      whereas in hippocampus glycine exerts dual modulatory roles on strychnine
      sensitive glycine receptors and on the strychnine-insensitive glycineB site of
      the N-methyl-D-aspartate receptor (NMDAR). In hippocampus, the synaptic
      availability of glycine is largely under control of glycine transporter 1
      (GlyT1). Since epilepsy is a disorder of disrupted network homeostasis affecting
      the equilibrium of various neurotransmitters and neuromodulators, we hypothesized
      that changes in hippocampal GlyT1 expression and resulting disruption of glycine
      homeostasis might be implicated in the pathophysiology of epilepsy. Using two
      different rodent models of temporal lobe epilepsy (TLE)--the intrahippocampal
      kainic acid model of TLE in mice, and the rat model of tetanic stimulation
      induced TLE--we first demonstrated robust overexpression of GlyT1 in the
      hippocampal formation, suggesting dysfunctional glycine signaling in epilepsy.
      Overexpression of GlyT1 in the hippocampal formation was corroborated in human
      TLE samples by quantitative real time PCR. In support of a role of dysfunctional
      glycine signaling in the pathophysiology of epilepsy, both the genetic deletion
      of GlyT1 in hippocampus and the GlyT1 inhibitor LY2365109 increased seizure
      thresholds in mice. Importantly, chronic seizures in the mouse model of TLE were
      robustly suppressed by systemic administration of the GlyT1 inhibitor LY2365109.
      We conclude that GlyT1 overexpression in the epileptic brain constitutes a new
      target for therapeutic intervention, and that GlyT1 inhibitors constitute a new
      class of antiictogenic drugs. These findings are of translational value since
      GlyT1 inhibitors are already in clinical development to treat cognitive symptoms
      in schizophrenia.

PMID- 26302657
TI  - Healthcare providers' knowledge, attitudes and practices towards medical male
      circumcision and their understandings of its partial efficacy in HIV prevention:
      Qualitative research in KwaZulu-Natal, South Africa.
AB  - BACKGROUND: Medical male circumcision has been shown to reduce HIV transmission
      to an uninfected male partner. In South Africa, medical male circumcision
      programs were rolled-out in 2010. OBJECTIVES: Prior to roll-out, we explored
      healthcare providers' knowledge, attitudes and practices about medical male
      circumcision and their understandings of partial efficacy for HIV prevention.
      DESIGN: We conducted qualitative research, using in-depth interviews. SETTING:
      Participants were from three rural and three urban primary healthcare clinics,
      randomly selected in eThekwini District, KwaZulu-Natal. PARTICIPANTS: 25
      healthcare providers (including nurse managers, nurses and counselors) were
      purposively selected from the clinics. METHODS: In-depth interviews were
      recorded, transcribed and translated. Independent researchers reviewed the
      transcripts and developed a codebook based on emergent themes, using thematic
      analysis. NVivo 8 was used to facilitate data management, coding and analysis.
      RESULTS: Although most providers had heard that medical male circumcision can
      reduce risk of HIV acquisition in men, most did not have accurate scientific
      understandings of this. Some providers had misperceptions about the
      limited/partial protection medical male circumcision offers. Many had concerns
      that their communities would misunderstand it, causing increased risky sexual
      behavior. CONCLUSIONS: These data provide a baseline of providers' understandings
      of medical male circumcision prior to roll-out, and can be used to compare
      current data and ensure accurate messaging to clients. Healthcare provider
      messaging should build client understandings of the meaning of partially
      efficacious technologies.

PMID- 26302658
TI  - The midwife's role in providing smoking cessation interventions for pregnant
      women: The views of midwives working with high risk, disadvantaged women in
      public sector antenatal services in South Africa.
AB  - OBJECTIVE: The purpose of this study was to assess the knowledge, attitudes,
      beliefs and current practices of South Africa midwives in relation to providing
      smoking cessation education or counselling to pregnant women. This was with a
      view to involving them in a potential smoking cessation intervention, targeting a
      sub-group of South African women who are at particularly high risk of the adverse
      pregnancy outcomes associated with smoking. DESIGN: A cross-sectional survey of
      midwives, supplemented by individual, in depth, qualitative interviews. SETTING:
      Public sector antenatal clinics serving this particular community of women in
      five of the major urban centres of South Africa. PARTICIPANTS: A total of 102
      midwives were surveyed across 29 antenatal clinics and 24 were interviewed.
      MEASUREMENTS: Self-administered survey and semi-structured, individual interviews
      describing constructs from the Theory of Planned Behaviour with respect to the
      provision of smoking cessation education/counselling, including: knowledge,
      attitudes, subjective norms and perceived behavioural control. FINDINGS: The
      majority of midwives accepted that providing smoking cessation advice was a part
      of their remit, perceived prevailing social norms to be supportive and were,
      overall, positively predisposed to participating in a smoking cessation
      intervention in antenatal clinics. However, the study identified a number of
      constraints to midwives fulfilling this role, which affected their perceived
      behavioural control. These included stressful working conditions, too little
      time, a dearth of educational resources and a lack of knowledge of best practice
      intervention methods and counselling skills. Perceived patient resistance to
      quitting was a further obstacle. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE:
      For the intervention to be accepted and adopted by midwives, it would need to
      offer them an opportunity to enhance their professional knowledge and expertise,
      provide them with attractive educational aids and take into account the very
      limited time they have for smoking education. Patient-centred, best practice
      methods for cessation counselling may help midwives overcome the problem of
      patient resistance and to engage smokers in constructive discussions about
      smoking with a greater prospect of success.

PMID- 26302659
TI  - Enzyme transition states from theory and experiment.

PMID- 26302660
TI  - Detection of DNA double-strand breaks in boron neutron capture reaction.
AB  - We evaluated DNA double-strand breaks (DSBs) induced by boron neutron capture
      reaction (BNCR) using plasmid DNA, boron solution, and gel electrophoresis. The
      amount of the linear form of DNA produced by DSBs increased with the neutron-beam
      irradiation dose. The amount of the open-circular form of DNA produced by single
      strand breaks (SSBs) increased with the neutron-beam irradiation dose and the
      (10)B concentration. The model facilitated quantification of BNCR-induced DSBs
      and SSBs, irrespective of the DNA repair mechanism. 

PMID- 26302661
TI  - Proteomic analysis of cellular response induced by boron neutron capture reaction
      in human squamous cell carcinoma SAS cells.
AB  - To understand the mechanism of cell death induced by boron neutron capture
      reaction (BNCR), we performed proteome analyses of human squamous tumor SAS cells
      after BNCR. Cells were irradiated with thermal neutron beam at KUR after
      incubation under boronophenylalanine (BPA)(+) and BPA(-) conditions. BNCR mainly
      induced typical apoptosis in SAS cells 24h post-irradiation. Proteomic analysis
      in SAS cells suggested that proteins functioning in endoplasmic reticulum, DNA
      repair, and RNA processing showed dynamic changes at early phase after BNCR and
      could be involved in the regulation of cellular response to BNCR. We found that
      the BNCR induces fragments of endoplasmic reticulum-localized lymphoid-restricted
      protein (LRMP). The fragmentation of LRMP was also observed in the rat tumor
      graft model 20 hours after BNCT treatment carried out at the National Nuclear
      Center of the Republic of Kazakhstan. These data suggest that dynamic changes of
      LRMP could be involved during cellular response to BNCR. 

PMID- 26302662
TI  - Neutron generator for BNCT based on high current ECR ion source with gyrotron
      plasma heating.
AB  - BNCT development nowadays is constrained by a progress in neutron sources design.
      Creation of a cheap and compact intense neutron source would significantly
      simplify trial treatments avoiding use of expensive and complicated nuclear
      reactors and accelerators. D-D or D-T neutron generator is one of alternative
      types of such sources for. A so-called high current quasi-gasdynamic ECR ion
      source with plasma heating by millimeter wave gyrotron radiation is suggested to
      be used in a scheme of D-D neutron generator in the present work. Ion source of
      that type was developed in the Institute of Applied Physics of Russian Academy of
      Sciences (Nizhny Novgorod, Russia). It can produce deuteron ion beams with
      current density up to 700-800 mA/cm(2). Generation of the neutron flux with
      density at the level of 7-8.10(10) s(-1) cm(-2) at the target surface could be
      obtained in case of TiD2 target bombardment with deuteron beam accelerated to 100
      keV. Estimations show that it is enough for formation of epithermal neutron flux
      with density higher than 10(9) s(-1) cm(-2) suitable for BNCT. Important
      advantage of described approach is absence of Tritium in the scheme. First
      experiments performed in pulsed regime with 300 mA, 45 kV deuteron beam directed
      to D2O target demonstrated 10(9) s(-1) neutron flux. This value corresponds to
      theoretical estimations and proofs prospects of neutron generator development
      based on high current quasi-gasdynamic ECR ion source.

PMID- 26302663
TI  - Hyaluronic acid as a potential boron carrier for BNCT: Preliminary evaluation.
AB  - Hyaluronic acid (HA), a nonimmunogenic, biocompatible polymer found in different
      biological tissues, has the potential to attach to CD44 receptors on the surface
      of certain cancer cells, where the receptor is overexpressed compared with normal
      cells. Boron-hyaluronic acid (BHA) was tested for its feasibility as a potential
      agent for BNCT. BHA with low-viscosity 30 kDa HA could be administered by
      intravenous injection. The compound showed a certain degree of cytotoxicity and
      accumulation in C6 rat glioma cells in vitro. Instability of the chelate bonds
      between boron and HA and/or insufficient specificity of CD44 receptors on C6
      cells to BHA could account for the insufficient in vitro accumulation. To ensure
      the future eligibility of BHA for BNCT experiments, using alternative tumor cell
      lines and chemically securing the chelate bonds or synthesizing BHA with boron
      covalently attached to HA might be required.

PMID- 26302664
TI  - Assessment of iodine nutritional status in the general population in the province
      of Jaen.
AB  - BACKGROUND AND OBJECTIVE: Iodine deficiency affecting both pregnant women and
      schoolchildren has been reported in Jaen. Iodine deficiency is one of the leading
      causes of thyroid dysfunction and goiter, and adequate iodine prophylaxis with
      iodized salt, milk, and dairy products, or iodine supplementation have been shown
      to significantly improve iodine status in pregnancy. The purpose of this study
      was to assess iodine nutritional status in the general population of a iodine
      deficient area with no previous institutional campaigns of iodine prophylaxis.
      MATERIAL AND METHODS: A descriptive, cross-sectional study. Urinary iodine levels
      were measured in subjects from the Jaen healthcare district. The data were
      stratified by sex and age groups, and a survey was conducted on iodized salt
      consumption. RESULTS: Median and mean urinary iodine levels were 110.59 mcg/L and
      130.11 mcg/L respectively. Urinary iodine levels were significantly higher in
      schoolchildren as compared to other age groups (161.52MUg/L vs 109.33MUg/L in
      subjects older than 65 years). Forty-three percent of the population had urinary
      iodine levels less than 100MUg/L, and 68% of women of childbearing age had levels
      less than 150MUg/L. CONCLUSIONS: Iodine nutritional status appears to be
      adequate, but the proportion of the population with urinary iodine levels less
      than 100MUg/L is still very high, and iodized salt consumption is much less
      common than recommended by the WHO.

PMID- 26302665
TI  - A lower cardiorespiratory fitness is associated to an unhealthy status among
      children and adolescents from Bogota, Colombia.
AB  - OBJECTIVE: Several studies have shown that low cardiorespiratory fitness (CRF) is
      a significant independent risk factor for future cardiometabolic disease in adult
      life. The aim of this study was to examine the relationship between CRF and
      health status in children and adolescents in Bogota, Colombia. METHODS: A cross
      sectional study was conducted in 921 children and adolescents aged 9-17 years
      living in the metropolitan area of the District of Bogota, Colombia (2,480m asl).
      CRF was assessed with the 20m shuttle run test (Course-Navette) according to
      ALPHA-FITNESS and FITNESSGRAM standards. Blood pressure, waist circumference, hip
      circumference, body composition (body fat percentage, fat body mass, and fat-free
      mass by bioimpedance), skin fold calipers, body mass index, and sexual maturity
      (Tanner) were used as indicators of physical health. RESULTS: After adjusting for
      sex, age, and sexual maturity, significant inverse relationships were seen
      between CRF and body mass index (r=-0.107), body fat percentage (r=-0.197), fat
      body mass (r=-0.159), skin fold (r=-0.246), and waist circumference (r=-0.169);
      P<.001. Schoolchildren with low CRF levels showed OR 6.06 (95% CI 3.98-9.24)
      increase in body fat by bioimpedance; OR 4.04 (95% CI 1.83-9.11) risk of
      overweight/obese by body mass index and OR 2.47 (95% CI 1.14-5.37) abdominal
      obesity due to increased waist circumference. CONCLUSION: Approximately two
      thirds of participants had a CRF level suggesting future cardiovascular disease.
      Early identification of children and adolescents with low CRF levels will allow
      for implementing interventions to prevent cardiometabolic disease in adulthood.

PMID- 26302666
TI  - Urinary sodium or potassium excretion and blood pressure in adults of Shandong
      province, China: preliminary results of the SMASH project.
AB  - The aim of the study was to estimate the urinary electrolyte excretion and assess
      the relationship between dietary sodium or potassium intake and blood pressure
      within a population of 18-69 adults in Shandong province, China. Random samples
      of 2184 adults enrolled in the Shandong and Ministry of Health Action on Salt
      reduction and Hypertension project were collected from 20 countries or districts.
      Electrolyte intake was estimated by 24-hour urine collections, and urinary volume
      or creatinine was measured to estimate the accuracy of the collection.
      Anthropometry was measured with standard procedures. Regression analysis was used
      to assess the relationship between electrolyte excretion and blood pressure. The
      mean sodium excretion was 241.8 +/- 7.9 mmol among men and 222.3 +/- 7.9 mmol
      among women, respectively. The 24-hour average potassium excretion was 39.9 +/-
      0.9 and 41.8 +/- 1.1 mmol, respectively. Some resident and geographic differences
      were found for 24-hour urinary electrolyte. Regression analysis showed increments
      of 1.15 mm Hg in systolic blood pressure and 0.67 mm Hg in diastolic blood
      pressure per gram increment in urinary sodium excretion. For each increment of 1
      g potassium excretion per day, there was a decrement of 0.81 mm Hg in systolic
      blood pressure and 0.76 mm Hg in diastolic blood pressure. The highest blood
      pressure was observed in the group with lowest potassium and the highest sodium
      excretion, which was 13.6 mm Hg in systolic blood pressure and 7.3 mm Hg in
      diastolic blood pressure difference from group with highest potassium excretion
      and lowest sodium excretion (P < .0001 for interaction). The Shandong and
      Ministry of Health Action on Salt reduction and Hypertension project results show
      a substantially higher sodium excretion and a lower potassium excretion than
      recommended in Shandong adults. The sodium or potassium intake is positively
      association with blood pressure. These results support the recommended approaches
      to lower the risk of hypertension, including lower sodium intake, higher
      potassium intake, and prevention and control of obesity.

PMID- 26302667
TI  - Neuropsychiatric Symptoms, Caregiver Burden and Distress in Behavioral-Variant
      Frontotemporal Dementia and Alzheimer's Disease.
AB  - BACKGROUND/AIMS: We aimed to compare caregiver burden and distress in behavioral
      variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD) and to
      investigate which factors contribute to caregivers' burden and distress. METHODS:
      Fifty patients and their caregivers were invited to participate. Among the
      patients, 20 had a diagnosis of bvFTD and 30 had AD. Caregivers and patients were
      statistically equivalent for age, sex, education and dementia severity according
      to Clinical Dementia Rating. The protocol included the Short Zarit Burden
      Inventory, the Neuropsychiatric Inventory (NPI), Disability Assessment for
      Dementia (DAD), the Cornell Scale for Depression in Dementia (CSDD),
      Addenbrooke's Cognitive Examination-Revised, the Executive Interview with 25
      Items, Direct Assessment of Functional Status and the Geriatric Anxiety Inventory
      (GAI). RESULTS: In the NPI, caregivers of bvFTD patients reported a higher
      presence and severity of neuropsychiatric symptoms and caregiver distress
      compared to caregivers of AD patients. There was no significant difference in the
      perceived burden. In bvFTD, DAD and GAI scores were significantly correlated with
      burden, whereas in AD, burden was correlated with CSDD and NPI scores.
      Psychiatric symptoms were associated with distress in both groups. CONCLUSIONS:
      Caregivers of bvFTD patients experienced higher levels of distress than
      caregivers of AD patients. Patients' functional limitations were associated with
      burden of caregivers of bvFTD patients, whereas neuropsychiatric symptoms were
      associated with caregiver strain in both groups.

PMID- 26302669
TI  - Randomised trial comparing the transversus abdominis plane block posterior
      approach or quadratus lumborum block type I with femoral block for postoperative
      analgesia in femoral neck fracture, both ultrasound-guided.
AB  - INTRODUCTION: A double-blind randomised controlled trial was conducted to compare
      the analgesic effect of the transversus abdominis plane block posterior approach
      or the quadratus lumborum block I versus femoral block, both ultrasound-guided.
      MATERIAL AND METHODS: Prospective study with parallel groups with 104 patients
      with neck of femur fracture undergoing hemiarthroplasty (although 7 participants
      did not finish the study). The inclusion criteria were patients older than 65
      years old, ASA I-III status, who required and gave their consent for
      hemiarthroplasty. The exclusion criteria were patients with known allergy to
      local anaesthetics, mental disability, peripheral neuropathy, a coagulopathy
      disorder, and those patients who received morphine, or a block was performed
      previous to the surgery. Each patient received one block followed by a spinal
      anaesthetic technique, performed by the anaesthetist. Pain was measured using a
      visual analogue score, sensory blockade using cold spray, and motor blockade,
      evaluating the leg movement. These were compared on arrival in recovery and at 6,
      12, 18, and 24h later. Total opioid amount administered in 24 hours, duration of
      stay in post-anaesthesia care unit, patient satisfaction, and adverse effects
      were also recorded. RESULTS: A lower visual analogue score was observed in the
      quadratus lumborum block group at 6, 12, 18 and 24h (3.7, 1.4, 0.8, 0.7 versus
      5.2, 4.6, 3.4, 2.6 in the femoral group, P<.01). Opioid use in 24h was lower in
      this group (9.7 versus 16.9mg in the femoral group, P<.01). The sensory and motor
      blockade, satisfaction, and adverse effects, were similar in both groups.
      CONCLUSIONS: Quadratus lumborum block is an effective analgesic option to be used
      in patients with neck of femur fracture. More clinical trials are required to
      validate this.

PMID- 26302668
TI  - Left brain cortical activity modulates stress effects on social behavior.
AB  - When subjected to stress, some individuals develop maladaptive symptoms whereas
      others retain normal behavior. The medial prefrontal cortex (mPFC) is known to
      control these adaptive responses to stress. Here, we show that mPFC neurons in
      the left hemisphere control stress effects on social behavior. Mice made socially
      avoidant by the stress of chronic social defeats showed depressed neural activity
      in the left mPFC. Photoactivation of these neurons reversed social avoidance and
      restored social activity. Despite social defeats, resilient mice with normal
      sociability showed normal firing rates in the left mPFC; however, photoinhibition
      of these neurons induced social avoidance. The same photomodulation administered
      to the right mPFC caused no significant effects. These results explain how
      stressed individuals develop maladaptive behaviors through left cortical
      depression, as reported in mood and anxiety disorders. 

PMID- 26302670
TI  - An fMRI investigation of the effects of culture on evaluations of stigmatized
      individuals.
AB  - Certain groups (e.g., women, older adults, and the economically disadvantaged)
      are universally stigmatized. Numerous studies, however, have identified cross
      cultural differences in the attitudes expressed toward stigmatized groups. These
      differences may potentially be due to existing cross-cultural dissimilarities in
      social status for some groups. The current study used fMRI to examine whether
      Chinese and Caucasian-American participants engage the same cognitive and
      affective mechanisms when perceiving stigmatized individuals with similarly low
      social status in both cultures (homeless individuals), but different cognitive
      and/or affective processes when evaluating stigmatized individuals whose status
      differs across cultures (older adults). Using a social neuroscience approach can
      provide unique insight into this question because the neural regions involved in
      cognitive and affective evaluations of stigmatized individuals have been well
      characterized. Results revealed that Chinese participants and Caucasian-American
      participants engaged similar patterns of negative affective processing associated
      with disgust (left anterior insula) when evaluating homeless individuals.
      Moreover, self-reported negative explicit attitudes toward homeless individuals
      were associated with increased activity in the insula. However, Chinese
      participants and Caucasian-American participants engaged increased activity in
      neural regions associated with status (ventral striatum) when they evaluated
      older adults. Moreover, self-reported attitudes toward older adults and ventral
      striatal activity were correlated with the extent to which participants reported
      being affiliated with their respective cultural traditions.

PMID- 26302671
TI  - Impact of sleep loss before learning on cortical dynamics during memory
      retrieval.
AB  - Evidence shows that sleep loss before learning decreases activation of the
      hippocampus during encoding and promotes forgetting. But it remains to be
      determined which neural systems are functionally affected during memory retrieval
      after one night of recovery sleep. To investigate this issue, we evaluated memory
      for pairs of famous people's faces with the same or different profession (i.e.,
      semantically congruent or incongruent faces) after one night of undisturbed sleep
      in subjects who either underwent 4hours of acute sleep restriction (ASR, N=20) or
      who slept 8hours the pre-training night (controls, N=20). EEG recordings were
      collected during the recognition memory task in both groups, and the cortical
      sources generating this activity localized by applying a spatial beamforming
      filter in the frequency domain. Even though sleep restriction did not affect
      accuracy of memory performance, controls showed a much larger decrease of alpha
      power relative to a baseline period when compared to sleep-deprived subjects.
      These group differences affected a widespread frontotemporoparietal network
      involved in retrieval of episodic/semantic memories. Regression analyses further
      revealed that associative memory in the ASR group was negatively correlated with
      alpha power in the occipital regions, whereas the benefit of congruency in the
      same group was positively correlated with delta power in the left lateral
      prefrontal cortex. Retrieval-related decreases of alpha power have been
      associated with the reactivation of material-specific memory representations,
      whereas increases of delta power have been related to inhibition of interferences
      that may affect the performance of the task. We can therefore draw the conclusion
      that a few hours of sleep loss in the pre-training night, though insufficient to
      change the memory performance, is sufficient to alter the processes involved in
      retrieving and manipulating episodic and semantic information. 

PMID- 26302672
TI  - Differential age-dependent associations of gray matter volume and white matter
      integrity with processing speed in healthy older adults.
AB  - Slower processing speed (PS), a highly robust feature of cognitive aging, is
      associated with white matter (WM) deterioration and gray matter volume (GMV)
      loss. Traditional linear regression models assume a constant relationship between
      brain structure and cognition over time. To probe for variation in the
      association between WM and GMV and PS over time, we used a novel sparse varying
      coefficient model on data collected from 126 relatively healthy older adults (67
      females, aged 58-85years) evaluated with MRI and a standardized
      neuropsychological test-battery. We found that WM microstructural differences
      indexed by fractional anisotropy values in the fronto-striatal tracts (internal
      and external capsule) showed a stronger association with PS before the age of
      70years. Contrastingly, GMV values of the left putamen and middle occipital gyrus
      were more strongly correlated with PS after 70years. Additionally, within GM and
      WM compartments, there was heterogeneity in the temporal sequence in which
      different cortical and subcortical elements were most strongly associated with
      PS. Together, these observations provide a more nuanced account of the
      relationships between different structural components of the aging brain and
      processing speed, a key cognitive domain affected in relatively healthy older
      adults. 

PMID- 26302673
TI  - The impact of motivation on race-based impression formation.
AB  - Affective biases toward racial out-group members, characterized by White
      perceivers' negative evaluations of Black individuals, prevail in U.S. culture.
      Such affective associations have been found to guide race-based impression
      formation. Accordingly, individuals may strive to resolve inconsistencies when
      perceiving targets violating their expectations. The current study focuses on the
      impact of evaluative incongruence on the activity of the dorsomedial prefrontal
      cortex (dmPFC) - a brain region previously shown to support impression formation.
      When asking participants to form impressions of positively and negatively
      evaluated Black and White individuals, we found preferential dmPFC activity in
      response to individuals paired with information that violates race-based
      affective associations. Importantly, individual differences in internal
      motivation to respond without prejudice (IMS) were found to shape the extent to
      which dmPFC activity indexes the interactive effects of race and affective
      associations during impression formation. Specifically, preferential dmPFC
      activity in response to evaluatively incongruent targets (i.e., Black-positive &
      White-negative) was present among participants with lower, but not those with
      higher, levels of IMS. Implications and future directions are discussed in the
      context of dmPFC involvement in social cognition.

PMID- 26302674
TI  - Inter-individual differences in the experience of negative emotion predict
      variations in functional brain architecture.
AB  - Current evidence suggests that two spatially distinct neuroanatomical networks,
      the dorsal attention network (DAN) and the default mode network (DMN), support
      externally and internally oriented cognition, respectively, and are functionally
      regulated by a third, frontoparietal control network (FPC). Interactions among
      these networks contribute to normal variations in cognitive functioning and to
      the aberrant affective profiles present in certain clinical conditions, such as
      major depression. Nevertheless, their links to non-clinical variations in
      affective functioning are still poorly understood. To address this issue, we used
      fMRI to measure the intrinsic functional interactions among these networks in a
      sample of predominantly younger women (N=162) from the Human Connectome Project.
      Consistent with the previously documented dichotomous motivational orientations
      (i.e., withdrawal versus approach) associated with sadness versus anger, we
      hypothesized that greater sadness would predict greater DMN (rather than DAN)
      functional dominance, whereas greater anger would predict the opposite. Overall,
      there was evidence of greater DAN (rather than DMN) functional dominance, but
      this pattern was modulated by current experience of specific negative emotions,
      as well as subclinical depressive and anxiety symptoms. Thus, greater levels of
      currently experienced sadness and subclinical depression independently predicted
      weaker DAN functional dominance (i.e., weaker DAN-FPC functional connectivity),
      likely reflecting reduced goal-directed attention towards the external perceptual
      environment. Complementarily, greater levels of currently experienced anger and
      subclinical anxiety predicted greater DAN functional dominance (i.e., greater DAN
      FPC functional connectivity and, for anxiety only, also weaker DMN-FPC coupling).
      Our findings suggest that distinct affective states and subclinical mood symptoms
      have dissociable neural signatures, reflective of the symbiotic relationship
      between cognitive processes and emotional states. 

PMID- 26302675
TI  - Simultaneous head tissue conductivity and EEG source location estimation.
AB  - Accurate electroencephalographic (EEG) source localization requires an electrical
      head model incorporating accurate geometries and conductivity values for the
      major head tissues. While consistent conductivity values have been reported for
      scalp, brain, and cerebrospinal fluid, measured brain-to-skull conductivity ratio
      (BSCR) estimates have varied between 8 and 80, likely reflecting both inter
      subject and measurement method differences. In simulations, mis-estimation of
      skull conductivity can produce source localization errors as large as 3cm. Here,
      we describe an iterative gradient-based approach to Simultaneous tissue
      Conductivity And source Location Estimation (SCALE). The scalp projection maps
      used by SCALE are obtained from near-dipolar effective EEG sources found by
      adequate independent component analysis (ICA) decomposition of sufficient high
      density EEG data. We applied SCALE to simulated scalp projections of 15cm(2)
      scale cortical patch sources in an MR image-based electrical head model with
      simulated BSCR of 30. Initialized either with a BSCR of 80 or 20, SCALE estimated
      BSCR as 32.6. In Adaptive Mixture ICA (AMICA) decompositions of (45-min, 128
      channel) EEG data from two young adults we identified sets of 13 independent
      components having near-dipolar scalp maps compatible with a single cortical
      source patch. Again initialized with either BSCR 80 or 25, SCALE gave BSCR
      estimates of 34 and 54 for the two subjects respectively. The ability to
      accurately estimate skull conductivity non-invasively from any well-recorded EEG
      data in combination with a stable and non-invasively acquired MR imaging-derived
      electrical head model could remove a critical barrier to using EEG as a sub-cm(2)
      scale accurate 3-D functional cortical imaging modality.

PMID- 26302676
TI  - Serine 403-phosphorylated p62/SQSTM1 immunoreactivity in inclusions of
      neurodegenerative diseases.
AB  - Protein inclusions in neurodegenerative diseases are associated with p62, which
      has an important role in autophagic clearance of polyubiquitinated proteins.
      Selective autophagy is regulated by S403-phosphorylation of p62, and S403
      phosphorylated p62 (S403-phos-p62) accumulates in Atg5 conditional knockout
      (Atg5CKO) mice in which autophagosome formation is impaired. We performed
      immunohistochemical tests for the presence of S403-phos-p62 in postmortem brain
      of neurodegenerative disease cases, and found accumulations in amyotrophic
      lateral sclerosis and Alzheimer's disease tissues. In Atg5CKO and HD190QG
      (Huntington's disease model) mice, however, we found a postmortem decrease in
      S403-phos-p62 immunoreactivity, suggesting that post-mortem changes should be
      considered when interpreting human data. 

PMID- 26302677
TI  - Higher gait speed and smaller sway area decrease the risk for decline in higher
      level functional capacity among middle-aged and elderly women.
AB  - OBJECTIVE: This study assessed whether physical function can indicate a risk of
      decline in higher-level functional capacity. METHODS: Data were derived from the
      National Institute for Longevity Sciences-Longitudinal Study of Aging. Subjects
      comprised 466 men and 495 women aged 40-79 years at baseline (1997-2000), whose
      total score for the Tokyo Metropolitan Institute of Gerontology Index of
      Competence (TMIG-IC) at baseline was >=11 and who participated in the follow-up
      survey. Baseline physical function examination included grip strength,
      comfortable gait speed, and sway area with eyes open. A decline in higher-level
      functional capacity was defined as a >=2-point decrease in the TMIG-IC score
      after 14 years. The odds ratios (OR) and 95% confidence intervals (CI) for
      decline in the TMIG-IC score for 14 years according to a 1-standard deviation
      (SD) increase in physical function measurements at baseline were estimated.
      RESULTS: Subjects with decreased TMIG-IC scores included 78 (16.7%) men and 80
      (16.2%) women. In women, the multivariate-adjusted OR (95% CI) for a TMIG-IC
      score decrease with a 1-SD increase in comfortable gait speed was 0.68 (0.50
      0.92; p=0.013), and that with a 1-SD increase in sway area with eyes open was
      1.49 (1.17-1.90; p=0.001). Grip strength was not associated with TMIG-IC score
      decline. None of the physical performance measures affected TMIG-IC score
      declines in men. CONCLUSION: These results suggest that gait speed decreases and
      sway area increases might predict a risk of decline in higher-level functional
      capacity among middle-aged and elderly women.

PMID- 26302678
TI  - Looking Beyond Chronological Age: Current Knowledge and Future Directions in the
      Study of Subjective Age.
AB  - The notion of the heterogeneity of aging goes along with the awareness that every
      person experiences aging differently. Over the past years, scholars have
      emphasized that the assessment of these subjective experiences of aging
      contributes to our understanding of a range of psychological and physiological
      processes and outcomes among older adults. One construct frequently used in this
      context is subjective age, that is, how old or young a person feels. Subjective
      age has been shown to be an important correlate as well as a predictor of markers
      of successful aging such as well-being, health, and longevity. However, less is
      known about the antecedents of subjective age and the mechanisms underlying the
      relationship between feeling younger and positive developmental outcomes. This
      article briefly summarizes and critically evaluates the empirical evidence on
      this topic and makes suggestions on how to address and potentially overcome
      currently existing theoretical, methodological, and psychometric challenges.
      Based on the discussion of these challenges, the paper provides directions for
      future research by outlining underexplored topics such as intraindividual
      variability and determinants of subjective age, the match between objective age
      indicators and subjective age, and how subjective age maps on behavior and
      functioning. 

PMID- 26302679
TI  - Granuloma formation after oil-soluble vitamin D injection for lip augmentation -
      case report.

PMID- 26302680
TI  - Bank voles (Myodes glareolus) and house mice (Mus musculus musculus; M. m.
      domesticus) in Europe are each parasitized by their own distinct species of
      Aspiculuris (Nematoda, Oxyurida).
AB  - The molecular phylogeny and morphology of the oxyuroid nematode genus Aspiculuris
      from voles and house mice has been examined. Worms collected from Myodes
      glareolus in Poland, Eire and the UK are identified as Aspiculuris tianjinensis,
      previously known only from China, while worms from Mus musculus from a range of
      locations in Europe and from laboratory mice, all conformed to the description of
      Aspiculuris tetraptera. Worms from voles and house mice are not closely related
      and are not derived from each other, with A. tianjinensis being most closely
      related to Aspiculuris dinniki from snow voles and to an isolate from Microtus
      longicaudus in the Nearctic. Both A. tianjinensis and A. tetraptera appear to
      represent recent radiations within their host groups; in voles, this radiation
      cannot be more than 2 million years old, while in commensal house mice it is
      likely to be less than 10,000 years old. The potential of Aspiculuris spp. as
      markers of host evolution is highlighted.

PMID- 26302682
TI  - Transition metal-free aroylation of NH-sulfoximines with methyl arenes.
AB  - A novel protocol towards N-aroylated sulfoximines from NH-sulfoximines and methyl
      arenes was herein demonstrated. The reaction took place in the presence of
      elemental iodine, requiring no external organic solvents, transition metal
      catalysts or ligands. The aroylated products were obtained from the oxidative
      transformation in moderate to excellent yields (up to 94% yield) with a broad
      substrate scope (35 examples) through a radical pathway. 

PMID- 26302681
TI  - ESR1 polymorphisms and statin therapy: a sex-specific approach.
AB  - Lipid-lowering therapy has shown a high degree of variability in clinical
      response and there is evidence that the variability in drug response between
      individuals is due to genetic factors. Thirteen single nucleotide polymorphisms
      (SNPs) within the ESR1 gene were evaluated with basal lipid and lipoprotein
      levels, as well as response to lipid-lowering therapy, in 495
      hypercholesterolemic individuals of European descent receiving simvastatin or
      atorvastatin. Significant associations were detected between rs4870061 (P=0.040,
      corrected P-value (PC)=0.440), rs1801132 (P=0.002, PC=0.022) and the SNP
      rs3020314 (P=0.013, PC=0.143) with triglyceride (TG) baseline levels. The
      rs4870061 was also associated with high-density lipoprotein cholesterol (HDL-C)
      baseline levels (P=0.045, PC=0.495). Regarding statin efficacy, rs2234693 C/C was
      associated with greater HDL-C increase (P=0.037; PC=0.407) and rs3798577 T allele
      was associated with greater total cholesterol (TC) reduction (P=0.019; PC=0.209)
      and greater TG reduction (P=0.026; PC=0.286). These associations suggest that
      ESR1 polymorphisms are in part responsible for the TC, HDL-C and TG variation
      levels and this effect may be sex-specific.

PMID- 26302683
TI  - Genotype GG of rs895819 Functional Polymorphism Within miR-27a Might Increase
      Genetic Susceptibility to Colorectal Cancer in Han Chinese Population.
AB  - BACKGROUND: MicroRNA-27a (miR-27a) is supposed to be an oncogene in various types
      of cancers, and genetic variation of miR-27a might result in aberrant expression
      and abnormal second structure of mature-miR-27a, contributing to elevated genetic
      risk and poor prognosis for colorectal cancer (CRC). METHODS: In order to explore
      the possible association between rs895819 within miR-27a and CRC in Han Chinese
      population, we investigated the genotype distributions of rs895819 in 508 CRC
      cases and 562 healthy check-up controls using TaqMan genotype discrimination
      system, and analyzed the possible association between them. Odds ratio (OR) and
      95% confidential interval (95% CI) were used to assess the strength between
      allele and genotype of the locus and risk of CRC. RESULTS: In our study, we found
      that genotype GG of rs895819 was significantly associated with an increased risk
      for CRC (17.1% vs. 11.6%, adjusted OR = 1.546, 95% CI = 1.070-2.236), and allele
      A carrier (AA/AG) was significantly associated with a decreased risk for CRC
      (82.9% vs. 89.4%, adjusted OR = 0.63, 95% CI = 0.446-0.893). In addition, a
      significant association was observed between genotype GG and larger tumor size
      (>5 cm; P < 0.001), and allele G was significantly associated with higher
      pathological stage (TNM-III) (P = 0.008). CONCLUSION: These results indicated
      that miR-27a might be involved in the development and progression of CRC,
      genotype GG within rs895819 might be a genetic susceptible factor for CRC.
      Further multicentral, large sample size, and well-designed epidemiological study
      as well as functional study are warrant to verify our findings.

PMID- 26302684
TI  - Smoking, smoking cessation, and fracture risk in elderly women followed for 10
      years.
AB  - This study examines the impact of smoking and smoking cessation on fracture risk
      in 75-year-old women followed for 10 years. Smoking increased fracture risk,
      especially for vertebral fractures. Smoking cessation decreased the risk for
      vertebral fractures but not for other fracture types. INTRODUCTION: The purpose
      of this study was to examine effects of smoking and smoking cessation on fracture
      risk. METHODS: This prospective observational population-based study followed
      1033 women during 10 years from age 75. Data regarding smoking were collected at
      age 75. Hazard ratios (HRs) and 95 % confidence intervals for fracture were
      calculated using competing risks proportional hazards regression. RESULTS: Both
      former smokers and current smokers had an increased risk for any fracture (HR
      1.30; 1.03-1.66, and HR 1.32; 1.01-1.73, respectively) and any osteoporotic
      fracture (hip, proximal humerus, distal radius, vertebra) (HR 1.31; 1.01-1.70 and
      HR 1.49; 1.11-1.98, respectively) compared to non-smokers. Former smokers had an
      increased risk for proximal humerus fractures (HR 2.23; 1.35-3.70), and current
      smokers had an increased risk for vertebral fractures (HR 2.30; 1.57-3.38)
      compared to non-smokers. After adjustment for weight, previous fractures, alcohol
      habits, bone mineral density (BMD), use of corticoids, vitamin D,
      bisphosphonates, and previous falls, former smokers had an increased risk for
      proximal humerus fracture (HR 2.07; 1.19-3.57) and current smokers had an
      increased risk for osteoporotic (HR 1.47; 1.05-2.05) and vertebral fractures (HR
      2.50; 1.58-3.95) compared to non-smokers. Former smokers had a decreased risk for
      vertebral fractures, but not for other types of fractures, compared to current
      smokers. CONCLUSIONS: Smoking increased the risk for fracture among elderly
      women, especially vertebral fractures. Smoking cessation decreased the risk for
      vertebral fractures but not for other types of fractures.

PMID- 26302685
TI  - Identification of a novel HLA-B*40 allele, HLA-B*40:229, in a Chinese individual.
AB  - The novel HLA-B*40:229 allele shows one nucleotide difference from B*40:02:01 in
      exon 2 at nucleotide position 97 (C -> T). 

PMID- 26302686
TI  - Wing trait-inversion associations in Drosophila subobscura can be generalized
      within continents, but may change through time.
AB  - Clinal variation is one of the most emblematic examples of the action of natural
      selection at a wide geographical range. In Drosophila subobscura, parallel clines
      in body size and inversions, but not in wing shape, were found in Europe and
      South and North America. Previous work has shown that a bottleneck effect might
      be largely responsible for differences in wing trait-inversion association
      between one European and one South American population. One question still
      unaddressed is whether the associations found before are present across other
      populations of the European and South American clines. Another open question is
      whether evolutionary dynamics in a new environment can lead to relevant changes
      in wing traits-inversion association. To analyse geographical variation in these
      associations, we characterized three recently laboratory founded D. subobscura
      populations from both the European and South American latitudinal clines. To
      address temporal variation, we also characterized the association at a later
      generation in the European populations. We found that wing size and shape
      associations can be generalized across populations of the same continent, but may
      change through time for wing size. The observed temporal changes are probably due
      to changes in the genetic content of inversions, derived from adaptation to the
      new, laboratory environment. Finally, we show that it is not possible to predict
      clinal variation from intrapopulation associations. All in all this suggests
      that, at least in the present, wing traits-inversion associations are not
      responsible for the maintenance of the latitudinal clines in wing shape and size.

PMID- 26302687
TI  - Modelling the Future: System Dynamics in the Cutaneous Malignant Melanoma Care
      Pathway.
AB  - Incidence rates for cutaneous malignant melanoma are increasing worldwide.
      Estimates of the future number of melanoma cases are important for strategic
      planning of the care pathway. The aim of this study was to use system dynamics
      modelling to evaluate the long-term effects of changes in incidence, population
      growth and preventive interventions. Historical data on invasive melanoma cases
      in Western Sweden from 1990 to 2006 were obtained. Using computer simulation
      software, a model estimating the accumulated number of melanoma cases for 2014 to
      2023 was developed. Five future scenarios were designed: stable incidence,
      business-as-usual, 25% reduced patient's delay, 50% reduced doctor's delay, and a
      combination of the last two, called improved overall secondary prevention. After
      10 years, improved overall secondary prevention would have resulted in a 42%
      decrease in melanomas > 4 mm and a 10% increase in melanomas <= 1 mm, compared
      with business-as-usual. System dynamics is a valuable tool, which can help
      policymakers choose the preventive interventions with the greatest impact. 

PMID- 26302688
TI  - Production of bioactive chicken (Gallus gallus) follistatin-type proteins in E.
      coli.
AB  - Follistatin (FST) is a cysteine-rich autocrine glycoprotein and plays an
      important role in mammalian prenatal and postnatal development. FST binds to and
      inhibit myostatin (MSTN), a potent negative regulator of skeletal muscle growth,
      and FST abundance enhances muscle growth in animals via inhibition of MSTN
      activity. The objective of this study was to produce biologically active, four
      chicken FST-type proteins in an Escherichia coli expression system. Gibson
      assembly cloning method was used to insert the DNA fragments of four FST-type
      proteins, designated as FST288, NDFSD1/2, NDFSD1, and NDFSD1/1, into pMALc5x
      vector downstream of the maltose-binding protein (MBP) gene, and the plasmids
      containing the inserts were eventually transformed into Shuffle E. coli strain
      for protein expression. We observed a soluble expression of the four MBP-fused
      FST-type proteins, and the proteins could be easily purified by the combination
      of amylose and heparin resin affinity chromatography. MBP-fused FST-type proteins
      demonstrated their affinity to anti-FST antibody. In an in vitro reporter gene
      assay to examine their potencies and selectivities to different ligands (MSTN,
      GDF11, and activin A), the four FST-type proteins (MBP-FST288, MBP-NDFSD1/2, MBP
      NDFSD1, and MBP-NDFSD1/1) showed different potency and selectivity against the
      three ligands from each other. Ligand selectivity of each FST-type proteins was
      similar to its counterpart FST-type protein of eukaryotic origin. In conclusion,
      we could produce four FST-type proteins having different ligand selectivity in E.
      coli, and the results imply that economic production of a large amount of FST
      type proteins with different ligand selectivity is possible to examine their
      potential use in meat-producing animals. 

PMID- 26302689
TI  - I'm in an NP State of Mind: A Tribute to Dr. Henry K. Silver on the 50th
      Anniversary of the Nurse Practitioner Profession.

PMID- 26302690
TI  - History of T-cain: a local anesthetic developed and manufactured in Japan.
AB  - In many anesthesia textbooks written in English, lidocaine, tetracaine,
      bupivacaine, ropivacaine, and chloroprocaine are listed as useful local
      anesthetics for spinal anesthesia. In contrast, T-cain is not included in these
      lists, even though it has been reported to be suitable for spinal anesthesia in
      Japan. T-cain was developed as a local anesthetic in the early 1940s by Teikoku
      Kagaku Sangyo Inc. in Itami, Japan, by replacing a methyl group on tetracaine
      (Pantocaine((r))) with an ethyl group. T-cain was clinically approved for topical
      use in Japan in November 1949, and a mixture of dibucaine and T-cain (Neo
      Percamin S((r))) was approved for spinal use in May 1950. Simply because of a
      lack of foreign marketing strategy, T-cain has never attracted global attention
      as a local anesthetic. However, in Japan, T-cain has been used topically or
      intrathecally (as Neo-Percamin S((r))) for more than 60 years. Other than the
      side effects generally known for all local anesthetics, serious side effects have
      not been reported for T-cain. In fact, several articles have reported that T-cain
      decreases the neurotoxicity of dibucaine. In this historical review, the
      characteristics of T-cain and its rise to become a major spinal anesthetic in
      Japan are discussed.

PMID- 26302691
TI  - In reply: Videolaryngoscope for intubation during chest compression.

PMID- 26302692
TI  - Effectiveness of retigabine against levobupivacaine-induced central nervous
      system toxicity: a prospective, randomized animal study.
AB  - PURPOSE: KCNQ2/3 channels play an important role in controlling neuronal
      excitability. Agents that decrease KCNQ2/3 current amplitudes are proconvulsant,
      whereas KCNQ2/3 current enhancers are anticonvulsant. Levobupivacaine is able to
      block the KCNQ2/3 channels and enhance neuronal excitation, whereas retigabine is
      able to reopen the channels and thus reduce overexcitation of neurons. In this
      study, we aimed to determine if retigabine is able to abolish local-anesthetic
      induced seizures. METHODS: Twenty New Zealand rabbits were randomly divided into
      two groups of ten. Levobupivacaine (0.5 %) was infused into conscious rabbits via
      the marginal ear vein at 8 ml/kg/h until the rabbits seized, and 5 mg/kg of
      retigabine were injected intravenously to terminate the seizure. The
      corresponding volume of saline was used as a control. The behavior of and the
      electroencephalogram (EEG) for each rabbit were continually monitored. Before
      levobupivacaine infusion, the rabbits were placed in a prostrate position calmly
      on the experimental platform, and the EEG pattern exhibited beta waves.
      Intravenous levobupivacaine induced a typical EEG seizure characterized by
      multiple spike and slow wave complexes. The EEG changes were accompanied by
      behavioral convulsions which were characterized by clonic activity and
      opisthotonus. RESULTS: Retigabine effectively terminated the electrographic and
      behavioral seizures. After receiving 5 mg/kg of retigabine, the animals became
      drowsy, and the EEG changed to delta waves. CONCLUSIONS: We propose that KCNQ2/3
      channels play an important role in levobupivacaine-induced central nervous system
      toxicity, and a KCNQ2/3 channel activator may be used to treat levobupivacaine
      induced convulsions.

PMID- 26302694
TI  - Lithium-doping inverts the nanoscale electric field at the grain boundaries in
      Cu2ZnSn(S,Se)4 and increases photovoltaic efficiency.
AB  - Passive grain boundaries (GBs) are essential for polycrystalline solar cells to
      reach high efficiency. However, the GBs in Cu2ZnSn(S,Se)4 have less favorable
      defect chemistry compared to CuInGaSe2. Here, using scanning probe microscopy we
      show that lithium doping of Cu2ZnSn(S,Se)4 changes the polarity of the electric
      field at the GB such that minority carrier electrons are repelled from the GB.
      Solar cells with lithium-doping show improved performance and yield a new
      efficiency record of 11.8% for hydrazine-free solution-processed Cu2ZnSn(S,Se)4.
      We propose that lithium competes for copper vacancies (forming benign
      isoelectronic LiCu defects) decreasing the concentration of ZnCu donors and
      competes for zinc vacancies (forming a LiZn acceptor that is likely shallower
      than CuZn). Both phenomena may explain the order of magnitude increase in
      conductivity. Further, the effects of lithium doping reported here establish that
      extrinsic species are able to alter the nanoscale electric fields near the GBs in
      Cu2ZnSn(S,Se)4. This will be essential for this low-cost Earth abundant element
      semiconductor to achieve efficiencies that compete with CuInGaSe2 and CdTe. 

PMID- 26302695
TI  - Silicification-induced cell aggregation for the sustainable production of H2
      under aerobic conditions.
AB  - Photobiological hydrogen production is of great importance because of its promise
      for generating clean renewable energy. In nature, green algae cannot produce
      hydrogen as a result of the extreme sensitivity of hydrogenase to oxygen.
      However, we find that silicification-induced green algae aggregates can achieve
      sustainable photobiological hydrogen production even under natural aerobic
      conditions. The core-shell structure of the green algae aggregates creates a
      balance between photosynthetic electron generation and hydrogenase activity, thus
      allowing the production of hydrogen. This finding provides a viable pathway for
      the solar-driven splitting of water into hydrogen and oxygen to develop green
      energy alternatives by using rationally designed cell-material complexes. 

PMID- 26302696
TI  - [Diagnostic value of selective anorexia in pathological weight loss].
AB  - PURPOSE: The diagnostic value of selective anorexia is debated. Some authors have
      suggested an association between meat aversion and cancer, but most do not use it
      as a diagnostic tool. We aimed to characterize anorexia of different diseases to
      search for an association between selective aversions and diagnostic groups.
      METHODS: All the patients admitted to three departments of a teaching hospital
      were included consecutively for 22months if they had more than 10 % weight loss
      in less than one year. Patients were excluded if history taking was not reliable,
      or if they suffered from anorexia nervosa. We compiled diagnoses at discharge and
      validated them six months later. We used logistic regression to identify
      independent factors associated with selective anorexia. RESULTS: Inclusion
      criteria were met in 106patients (female 44 %, median age 65years). Most frequent
      diagnoses were: cancer (36 %), infection (35 %), digestive diseases (19 %), non
      organic diseases (21 %). Recent selective anorexia was found in 46 % of the
      cases. It was significantly associated with female gender (P=0.002), marginally
      with young age (P=0.069) and long duration of weight loss (P=0.079). Opioid use
      at admission was negatively associated with selective anorexia (P=0.001). No
      specific diagnostic category was found to be associated. CONCLUSION: Selective
      anorexia does not appear to be a useful symptom to investigate pathological
      weight loss. It behaves more like a non-specific reactivation by current disease
      of earlier latent personal food aversions.

PMID- 26302697
TI  - Synthetic ACTH Is Not Superior to Prednisolone for Infantile Spasms: Randomized
      Clinical Trials and Tribulations.

PMID- 26302699
TI  - Predictors of Length of Stay in Children Admitted for Presurgical Evaluation for
      Epilepsy Surgery.
AB  - RATIONALE: One challenge for families whose children are undergoing presurgical
      evaluation for epilepsy surgery is the unpredictable length of hospitalization
      for video-electroencephalograph monitoring. The goal of this study was to
      retrospectively evaluate length of stay in children admitted for presurgical
      evaluation at a tertiary referral center. METHODS: Duration of stay for children
      with medically intractable epilepsy admitted for presurgical evaluation to the
      Pediatric Epilepsy Monitoring Unit at Mayo Clinic Rochester between 2010 and 2013
      was evaluated retrospectively. RESULTS: Of 140 children, surgical candidacy was
      determined in 122 (87.1%) (72 candidates, 50 noncandidates). The mean length of
      stay was 4.0 +/- 3.7 days and was not predicted by candidacy for surgery, age at
      monitoring, duration of epilepsy, number of antiepileptic drugs at admission, or
      focal/hemispheric magnetic resonance imaging abnormality. Shorter length of stay
      was predicted by younger age at epilepsy onset (P < 0.05) and shorter interval
      since most recent seizure (P = 0.001). Subtraction ictal single-photon emission
      computed tomography coregistered to magnetic resonance imaging was performed in
      43 (35.2%) children, and correlated with longer length of stay (mean 5.1 +/- 4.1
      days for subtraction ictal single-photon emission computed tomography
      coregistered to magnetic resonance imaging users versus 3.5 +/- 3.3 days for
      nonusers, P = 0.022). Antiepileptic drugs were reduced either upon or after
      admission in 67 (54.9%) children, and the length of stay was significantly longer
      in these patients (mean 5.5 +/- 4.1 days if antiepileptic drugs were reduced
      versus 2.2 +/- 2.1 days if not reduced, P < 0.001). CONCLUSIONS: Significant
      predictors of shorter length of stay include younger age at epilepsy onset,
      shorter interval from most recent seizure, lack of subtraction ictal single
      photon emission computed tomography coregistered to magnetic resonance imaging,
      and lack of need for AED reduction on or after admission.

PMID- 26302700
TI  - Late Cerebrovascular Complications After Radiotherapy for Childhood Primary
      Central Nervous System Tumors.
AB  - BACKGROUND: Brain radiotherapy plays a central role in the treatment of certain
      types of childhood primary central nervous system tumors. However, damage to
      surrounding normal brain tissue causes different acute and chronic medical and
      neurological complications. Despite the expected increase in number of childhood
      primary central nervous system tumor survivors, studies assessing the occurrence
      of late cerebrovascular complications, such as cavernoma, moyamoya, microbleeds,
      superficial siderosis, and stroke are sparse. METHODS: We undertook a
      retrospective consecutive case series review describing the occurrence and
      characteristics of late cerebrovascular complications in 100 survivors of
      childhood primary central nervous system tumors treated with radiotherapy.
      Demographic, clinical, and radiological findings including gradient echo brain
      magnetic resonance data were retrieved. RESULTS: Late cerebrovascular
      complications were found in 36 (36%) of the patients included in the study. Mean
      age at radiotherapy was 8.6 years (3-17) and at diagnosis was 23.9 years (3-38).
      The majority were males (21; 58%). The most common complications were microbleeds
      (29/36; 80.6%) and cavernomas 19 (52.8%). In seven (19.4%), late cerebrovascular
      complications were symptomatic: epilepsy (two), motor and language deficit (two),
      and sensorineural hearing loss and progressive ataxia (three) associated with
      cavernomas, stroke, and superficial siderosis, respectively. Follow-up length was
      associated with an increased diagnosis of late cerebrovascular complications (P <
      0.0001). Late cerebrovascular complications occurred more commonly in children
      treated with whole-brain radiation therapy (P = 0.046). Factors such as sex,
      chemotherapy, and histological type of tumor were not correlated with the
      occurrence of late cerebrovascular complications. CONCLUSION: Although not
      usually symptomatic, late cerebrovascular complications occur frequently in
      survivors of childhood primary central nervous system tumors treated with
      radiotherapy. Prolonged follow-up increases the probability of diagnosis. The
      impact and prognostic value of these late cerebrovascular complications is yet to
      be clarified.

PMID- 26302698
TI  - Brain Injury in the Preterm Infant: New Horizons for Pathogenesis and Prevention.
AB  - Preterm neonates are surviving with a milder spectrum of motor and cognitive
      disabilities that appear to be related to widespread disturbances in cell
      maturation that target cerebral gray and white matter. Whereas the preterm brain
      was previously at high risk for destructive lesions, preterm survivors now
      commonly display less severe injury that is associated with aberrant regeneration
      and repair responses that result in reduced cerebral growth. Impaired cerebral
      white matter growth is related to myelination disturbances that are initiated by
      acute death of premyelinating oligodendrocytes, but are followed by rapid
      regeneration of premyelinating oligodendrocytes that fail to normally mature to
      myelinating cells. Although immature neurons are more resistant to cell death
      than mature neurons, they display widespread disturbances in maturation of their
      dendritic arbors and synapses, which further contributes to impaired cerebral
      growth. Thus, even more mild cerebral injury involves disrupted repair mechanisms
      in which neurons and premyelinating oligodendrocytes fail to fully mature during
      a critical window in development of neural circuitry. These recently recognized
      distinct forms of cerebral gray and white matter dysmaturation raise new
      diagnostic challenges and suggest new therapeutic strategies to promote brain
      growth and repair.

PMID- 26302701
TI  - The Short-Term Effects of Ketogenic Diet on Cardiac Ventricular Functions in
      Epileptic Children.
AB  - OBJECTIVE: Our primary aim was to determine the short-term effects of a ketogenic
      diet on cardiac ventricular function in patients with refractory epilepsy.
      METHODS: Thirty-eight drug-resistant epileptic patients who were treated with a
      ketogenic diet were enrolled in this prospective study. Echocardiography was
      performed on all patients before beginning the ketogenic diet and after the sixth
      month of therapy. Two-dimensional, M-mode, color flow, spectral Doppler, and
      pulsed-wave tissue Doppler imaging measurements were performed on all patients.
      RESULTS: The median age of the 32 patients was 45.5 months, and 22 (57.8%) of
      them were male. Body weight, height, and body mass index increased significantly
      at the sixth month of therapy when compared with baseline values (P < 0.05).
      Baseline variables assessed by conventional M-mode echocardiography showed no
      significant difference at month 6 (P > 0.05). Doppler flow indices of mitral
      annulus and tricuspid annulus velocity of patients at baseline and month 6 showed
      no significant differences (P > 0.05). Tricuspid annular E/A ratio was lower at
      month 6 (P < 0.05). Although mitral annulus tissue Doppler imaging studies showed
      no significant difference (P > 0.05), there was a decrease in Ea velocity and
      Ea/Aa ratio gathered from tricuspid annulus at month 6 compared with baseline (P
      < 0.05). CONCLUSION: A 6-month duration ketogenic diet does not impair left
      ventricular functions in children with refractory epilepsy; however, it may be
      associated with a right ventricular diastolic dysfunction.

PMID- 26302702
TI  - Development of a simple IgE-independent anaphylactic model using buckwheat
      antigen and B-type CpG oligodeoxynucleotide from Streptococcus thermophilus.
AB  - We developed a severe anaphylactic model in mice using buckwheat antigen and B
      type CpG-oligodeoxynucleotides (CpG-ODNs) from Streptococcus thermophilus genome.
      In typical systemic anaphylaxis models, animals are challenged with large
      quantity of antigens via an intravenous (i.v.) route. Here, we showed a simple
      anaphylactic shock after challenge via intraperitoneal (i.p.) route. The i.p.
      method is simpler than i.v. administration and has a lower risk for failure. To
      generate this anaphylactic model, 5-week-old female BALB/c mice were first i.p.
      sensitized with buckwheat antigen mixed with B-type CpG-ODN. After 2 weeks, mice
      were challenged with antigen to induce anaphylactic shock, which was evaluated by
      scoring the severity symptoms and measuring serum levels of various proteins and
      splenic cell producing cytokines. Immunoglobulin (Ig)G2a production and
      interferon-gamma positive cells were markedly increased in mice immunized with
      antigen mixed with B-type CpG-ODN, whereas serum IgE levels were decreased by B
      type CpG-ODN. We also examined the effects of various ODNs (A, B and C-type CpG
      ODNs) and antigens (buckwheat, alpha-casein, beta-lactoglobulin and ovalbumin) on
      anaphylactic severity, and found that the combination of buckwheat and B-type CpG
      ODN induced the most intense anaphylactic shock. This model is expected to
      contribute to the study of the prevention of anaphylactic shock. 

PMID- 26302704
TI  - Three factors in the design and acquisition of language.
AB  - Recent advances in linguistic theory offer new proposals about the factors that
      are crucial to understanding the design and acquisition of language-the genetic
      endowment, experience, and principles not specific to the language faculty. Of
      particular interest is the third of these factors, whose importance is now widely
      recognized, raising questions about its character, its role in shaping the
      language faculty, and its impact on the future of linguistic research. WIREs Cogn
      Sci 2012 doi: 10.1002/wcs.1188 For further resources related to this article,
      please visit the WIREs website. 

PMID- 26302703
TI  - Genome-scale reconstruction of the metabolic network in Pseudomonas stutzeri
      A1501.
AB  - Pseudomonas stutzeri A1501 is an endophytic bacterium capable of nitrogen
      fixation. This strain has been isolated from the rice rhizosphere and provides
      the plant with fixed nitrogen and phytohormones. These interesting features
      encouraged us to study the metabolism of this microorganism at the systems-level.
      In this work, we present the first genome-scale metabolic model (iPB890) for P.
      stutzeri, involving 890 genes, 1135 reactions, and 813 metabolites. A combination
      of automatic and manual approaches was used in the reconstruction process.
      Briefly, using the metabolic networks of Pseudomonas aeruginosa and Pseudomonas
      putida as templates, a draft metabolic network of P. stutzeri was reconstructed.
      Then, the draft network was driven through an iterative and curative process of
      gap filling. In the next step, the model was evaluated using different
      experimental data such as specific growth rate, Biolog substrate utilization data
      and other experimental observations. In most of the evaluation cases, the model
      was successful in correctly predicting the cellular phenotypes. Thus, we posit
      that the iPB890 model serves as a suitable platform to explore the metabolism of
      P. stutzeri. 

PMID- 26302705
TI  - Intelligence.
AB  - Intelligence is the ability to learn from past experience and, in general, to
      adapt to, shape, and select environments. Aspects of intelligence are measured by
      standardized tests of intelligence. Average raw (number-correct) scores on such
      tests vary across the life span and also across generations, as well as across
      ethnic and socioeconomic groups. Intelligence can be understood in part in terms
      of the biology of the brain-especially with regard to the functioning in the
      prefrontal cortex. Measured values correlate with brain size, at least within
      humans. The heritability coefficient (ratio of genetic to phenotypic variation)
      is between 0.4 and 0.8. But genes always express themselves through environment.
      Heritability varies as a function of a number of factors, including socioeconomic
      status and range of environments. Racial-group differences in measured
      intelligence have been reported, but race is a socially constructed rather than
      biological variable. As a result, these differences are difficult to interpret.
      Different cultures have different conceptions of the nature of intelligence, and
      also require different skills in order to express intelligence in the
      environment. WIREs Cogn Sci 2012 doi: 10.1002/wcs.1193 For further resources
      related to this article, please visit the WIREs website. 

PMID- 26302706
TI  - Self-development.
AB  - The self is a multifaceted and complex construct. Each facet of the self and the
      interrelations between them are examined to understand 'what is self.' The
      neurocognitive, social, and cultural mechanisms underlying the development of
      self as extended in time and as a meaning system are further examined to
      understand how children come to acquire a sense of who they are. This includes
      when and how young children attain cognitive self-awareness, remember past
      experiences and imagine future happenings, and acquire a cultural self. The final
      analysis focuses on the executive function of the self with regard to how
      children come to emotionally react to and regulate the self. WIREs Cogn Sci 2012
      doi: 10.1002/wcs.1187 For further resources related to this article, please visit
      the WIREs website. 

PMID- 26302707
TI  - Religious thought and behavior.
AB  - While earlier approaches to religious thought and practice searched for 'magic
      bullet' approaches to explain religious thought and behavior, seeing it as an
      example of irrationality, illusion, integrative force, symbolism, or false
      explanations of origins, cognitive scientific approaches have suggested that we
      see it rather as an aggregate of the products of various cognitive mechanisms.
      Studies in the cognitive science of religion, informed by experimental work, have
      converged on a standard model of explaining religious thought and behavior by
      focussing on the role of minimally counter-intuitive concepts, agent and animacy
      detection, ritual representations, notions of contagion and contamination
      avoidance, theory of mind, coalitions, and moral intuitions. WIREs Cogn Sci 2012
      doi: 10.1002/wcs.1189 For further resources related to this article, please visit
      the WIREs website. 

PMID- 26302708
TI  - Disjunctivism, hallucinations, and metacognition.
AB  - Perceptual experiences have been construed either as representational mental
      states-Representationalism-or as direct mental relations to the external world
      Disjunctivism. Both conceptions are critical reactions to the so-called 'Argument
      from Hallucination', according to which perceptions cannot be about the external
      world, since they are subjectively indiscriminable from other, hallucinatory
      experiences, which are about sense-data or mind-dependent entities.
      Representationalism agrees that perceptions and hallucinations share their most
      specific mental kind, but accounts for hallucinations as misrepresentations of
      the external world. According to Disjunctivism, the phenomenal character of
      perceptions is exhausted by worldly objects and features, and thus must be
      different from the phenomenal character of hallucinations. Disjunctivism claims
      that subjective indiscriminability is not the result of a common experiential
      ground, but is because of our inability to discriminate, from the inside,
      hallucinations from perceptions. At first sight, Representationalism is more
      congenial to the way cognitive science deals with perception. However,
      empirically oriented revisions of Disjunctivism could be developed and tested by
      giving a metacognitive account of hallucinations. Two versions of this account
      can be formulated, depending on whether metacognition is understood as explicit
      metarepresentation or as implicit monitoring of first-order informational states.
      The first version faces serious objections, but the second is more promising, as
      it embodies a more realistic view of perceptual phenomenology as having both
      sensory and affective aspects. Affect-based phenomenology is constituted by
      various metacognitive feelings, such as the feeling of being perceptually
      confronted with the world itself, rather than with pictures or mere
      representations. WIREs Cogn Sci 2012 doi: 10.1002/wcs.1190 For further resources
      related to this article, please visit the WIREs website. 

PMID- 26302709
TI  - Instruction and cognition.
AB  - When teachers provide instruction to students, they provide opportunities for
      students to learn information. To be maximally effective, these opportunities
      should present information in ways that are compatible with the way the mind
      works. Using a US Department of Education Practice Guide as a structure for our
      review, we review 'second wave' cognitive science research on spaced learning,
      worked examples, coordinating visual and verbal representations, coordinating and
      concrete representations, quizzing, delayed Judgment of Learning, and explanatory
      reasoning. We also contextualize these lines of research within the contemporary
      K-12 classroom environment and constraints on teachers and school administrators.
      We close by advocating that all stakeholders in the instructional process also
      remember 'first wave' cognitive science findings, and also recommend more
      research on how specific motivational constructs could be brought to bear to
      encourage students to use these proven but effortful learning principles. WIREs
      Cogn Sci 2012 doi: 10.1002/wcs.1192 For further resources related to this
      article, please visit the WIREs website. 

PMID- 26302711
TI  - Catalytic Asymmetric Transfer Hydrogenation of Imines: Recent Advances.
AB  - In this review article recent developments in the asymmetric transfer
      hydrogenation of imines from 2008 up to today are presented. The main methodology
      involves either metal-catalyzed procedures in the presence of a chiral ligand or
      organocatalyzed technologies using a Hantzsch ester and a chiral BINOL-derived
      phosphoric acid. The most important procedures are collected, paying special
      attention to the application of this methodology in synthetic organic chemistry. 

PMID- 26302713
TI  - The evaluation of diastolic function using the diastolic wall strain (DWS) before
      and after radical surgery for congenital diaphragmatic hernia.
AB  - OBJECTIVE: The measurement of diastolic wall strain (DWS), a new method of
      evaluating cardiac diastolic function, was employed to evaluate ventricular
      diastolic function in patients with congenital diaphragmatic hernia (CDH).
      MATERIALS AND METHODS: Eighteen neonates with a CDH who were born and treated in
      our hospital between September 2009 and January 2013 were studied. The left
      ventricular posterior wall thickness during the systolic phase (PWs) and
      diastolic (PWd) phase was measured using M-mode imaging, and the DWS was
      calculated as (PWs-PWd)/PWs. The Tei index, the isovolumic relaxation time (IRT),
      and the fraction shortening (FS) were measured as indices of cardiac function in
      14, 15, and 18 cases, respectively. Cardiac function was measured before and
      after surgery. Statistical analyses were performed using the paired t test.
      RESULTS: The pre- and postoperative DWS, Tei index, IRT and FS values were 0.19
      +/- 0.06 and 0.26 +/- 0.11 (P < 0.01), 0.40 +/- 0.12 and 0.31 +/- 0.11 (P <
      0.05), 48 +/- 14 and 39 +/- 5.0 ms (P < 0.05), 30 +/- 7.7 and 34 +/- 7.4 % (P <
      0.05), respectively. CONCLUSION: The diastolic and systolic functions were not
      only measured by the Tei index, IRT and FS values, but also by the DWS value,
      which improved after surgery. The measurement of DWS is an easy and useful method
      for evaluating the diastolic function of CDH patients.

PMID- 26302714
TI  - Skin cover in epispadias repair by dorsal transposition of a ventral island flap:
      a modification of the Pippi Salle technique.
AB  - PURPOSE: To describe a technique for a reliable and cosmetic skin cover for
      epispadias repair. This is achieved using a ventral flap of prepuce and the
      penile skin. This is a modification of the technique described by Pippi Salle,
      who wrapped the penile shaft with the same flap, from one side with a resultant
      suture line on to the contralateral side of the penis. METHODS: Thirty-five
      children (18 with pure epispadias and 17 with exstrophy epispadias complex) who
      underwent epispadias repair by the described technique in our hospital were
      reviewed. In our technique, a ventral flap of prepuce and penile skin, as
      described by Pippi Salle, is developed and a button hole is made in the dartos
      fascia. This button hole is utilized to deliver the shaft ventrally which
      effectively brings the flap onto the dorsal aspect of the penis. The skin flap is
      then wrapped in toto around to provide a complete cover on the penile shaft with
      suture line on the ventral aspect. RESULTS: All the 35 children had satisfactory
      skin cover with a scarless dorsum of penis. Two children had immediate post
      operative ventral suture line breakdown, one requiring resuturing and the other
      healed spontaneously. CONCLUSION: The 'button hole' technique with dorsal
      transposition of the prepuce and skin flap effectively prevents the dorsal scar
      contracture by completely avoiding a longitudinal suture line dorsally. On the
      other hand, the healed ventral suture line is continuous with the scrotal midline
      raphe, giving a natural look. The overall result is a sturdy repair with a
      cosmetic appearance of the penis.

PMID- 26302712
TI  - Inhibition of microvesiculation sensitizes prostate cancer cells to chemotherapy
      and reduces docetaxel dose required to limit tumor growth in vivo.
AB  - Microvesicles shed from cells carry constituents of the cell cytoplasm,
      including, of importance in multidrug resistance to cancer chemotherapy, drugs
      that the tumor cell attempts to efflux. To see whether such drugs could be used
      at lower concentrations with the same efficacy, it was first shown that
      microvesiculation of prostate cancer (PCa) cells, PC3, could be inhibited
      pharmacologically with calpeptin (calpain inhibitor) and by siRNA (CAPNS1). In
      cells treated with docetaxel (DTX), this inhibition resulted in a third-fold
      increase in intracellular concentrations of DTX. As a result, 20-fold lower
      concentrations of DTX (5 nM) could be used, in the presence of calpeptin (20 MUM)
      inducing the same degree of apoptosis after 48 h in PC3 cells, as 100 nM of DTX
      alone. Inhibition of microvesiculation similarly improved combination
      chemotherapy (DTX and methotrexate). In a mouse xenograft model of PCa, DTX (0.1
      mg/kg) together with calpeptin (10 mg/kg), administered i.p., significantly
      reduced tumor volumes compared to DTX alone (0.1 mg/kg) and brought about the
      same reductions in tumor growth as 10 mg/kg of DTX alone. As well as further
      reducing vascularization, it also increased apoptosis and reduced proliferation
      of PC3 cells in tumor xenografts. 

PMID- 26302715
TI  - Luminescence from nearly isolated surface defects in silica nanoparticles.
AB  - A structured emission/excitation pattern, proper of isolated defects, arises in a
      vacuum from silica nanoparticles. The luminescence, centered around 3.0-3.5 eV,
      is characterised by a vibronic progression due to the phonon coupling with two
      localised modes of frequency  ~1370 cm(-1) and  ~360 cm(-1), and decays in about
      300 ns at 10 K. On increasing the temperature, the intensity and the lifetime
      decrease due to the activation of a non-radiative rate from the excited state.
      Concurrently, the temperature dependence of the lineshape evidences the low
      coupling with non-localised modes of the matrix (Huang-Rhys factor S ~ 0.2) and
      the poor influence of the inhomogeneous broadening. These findings outline an
      uncommon behaviour in the field of the optical properties of defects in amorphous
      solids, evidencing that the silica surface can allocate luminescent defects
      almost disentangled from the basal network.

PMID- 26302716
TI  - Happiness increases distraction by auditory deviant stimuli.
AB  - Rare and unexpected changes (deviants) in an otherwise repeated stream of task
      irrelevant auditory distractors (standards) capture attention and impair
      behavioural performance in an ongoing visual task. Recent evidence indicates that
      this effect is increased by sadness in a task involving neutral stimuli. We
      tested the hypothesis that such effect may not be limited to negative emotions
      but reflect a general depletion of attentional resources by examining whether a
      positive emotion (happiness) would increase deviance distraction too. Prior to
      performing an auditory-visual oddball task, happiness or a neutral mood was
      induced in participants by means of the exposure to music and the recollection of
      an autobiographical event. Results from the oddball task showed significantly
      larger deviance distraction following the induction of happiness. Interestingly,
      the small amount of distraction typically observed on the standard trial
      following a deviant trial (post-deviance distraction) was not increased by
      happiness. We speculate that happiness might interfere with the disengagement of
      attention from the deviant sound back towards the target stimulus (through the
      depletion of cognitive resources and/or mind wandering) but help subsequent
      cognitive control to recover from distraction. 

PMID- 26302717
TI  - Longitudinal development of match-running performance in elite male youth soccer
      players.
AB  - This study longitudinally examined age-related changes in the match-running
      performance of retained and released elite youth soccer players aged 8-18 years.
      The effect of playing position on age-related changes was also considered. Across
      three seasons, 263 elite youth soccer players were assessed in 1-29 competitive
      matches (988 player-matches). For each player-match, total distance and distances
      covered at age group-specific speed zones (low-speed, high-speed, sprinting) were
      calculated using 1 Hz or 5 Hz GPS. Mixed modeling predicted that match-running
      performance developed nonlinearly, with age-related changes best described with
      quadratic age terms. Modeling predicted that playing position significantly
      modified age-related changes (P < 0.05) and retained players covered
      significantly more low-speed distance compared with released players (P < 0.05),
      by 75 +/- 71 m/h (mean +/- 95% CI; effect size +/- 95% CI: 0.35 +/- 0.34). Model
      intercepts randomly varied, indicating differences between players in match
      running performance unexplained by age, playing position or status. These
      findings may assist experts in developing training programs specific to the match
      play demands of players of different ages and playing positions. Although
      retained players covered more low-speed distance than released players, further
      study of the actions comprising low-speed distance during match play is warranted
      to better understand factors differentiating retained and released players. 

PMID- 26302718
TI  - Looseness in bovine leather: microstructural characterization.
AB  - BACKGROUND: A substantial proportion of bovine leather production may be of poor
      quality, with the leather suffering from a characteristic known as looseness.
      This defect results in a poor visual appearance and greatly reduced value. The
      structural mechanism of looseness is not well understood. RESULTS: Samples of
      loose and tight bovine leather are characterized using small-angle X-ray
      scattering, ultrasonic imaging, and electron microscopy. The density of fibre
      packing and orientation of the fibrils are analysed. Tensile strength is also
      measured. Loose leather is characterized by more highly aligned collagen fibrils.
      This results in a weaker connection between the layers. There is a looser packing
      of the fibres in loose leather than in tight leather, with more gaps between
      fibre bundles, particularly in a region in the lower grain. This region is
      visible with in situ ultrasonic imaging. Loose leather has a higher tensile
      strength than tight leather. CONCLUSION: While a high degree of collagen fibril
      alignment is normally associated with strong leather, it has been shown that too
      much alignment results in loose leather. Understanding the physical basis of
      looseness is the first step in identifying looseness in hides and learning how to
      prevent looseness from developing during leather manufacture. (c) 2015 Society of
      Chemical Industry.

PMID- 26302719
TI  - Foreign body reactions may not influence the keloid recurrence.
AB  - PURPOSE: The foreign body reactions are comprised of macrophages and foreign body
      giant cells and are considered possible risk factors for recurrence in several
      conditions. The purpose of this study was to determine the effect of
      pathologically proven foreign body reactions on the recurrence of the auricular
      keloids. METHODS: This study was carried out in 76 cases in 70 patients reaching
      the pathologic diagnosis of auricular keloids from March 2006 to February 2012.
      Patients with auricular keloids were included in the study according to the
      following criteria: The keloid scar was caused by ear piercing and confirmed
      pathologically; surgical excision with primary closure was performed; and female
      patients who have not underwent any previous treatments. To compare any
      differences of recurrence rate between categorical variables (the
      presence/absence of foreign body reactions), Fisher's exact tests were used. All
      patients completed the treatment protocol with a follow-up interval of 18 months.
      RESULTS: Of these patients, 90.9% (69 keloids) had successful irradication of
      their auricular keloids, whereas 9.2% (seven keloids) had recurrences. Of the
      seven recurrent cases, two exhibited foreign body reactions at pathology, while
      five revealed no foreign body reactions (28.6% vs. 71.4%, P = 0.092).
      CONCLUSIONS: Detection of foreign body reactions in keloid tissue may not predict
      recurrence in auricular keloids.

PMID- 26302720
TI  - Insulin-Like Growth Factor 1 Activates PI3k/Akt Signaling to Antagonize Lumbar
      Disc Degeneration.
AB  - BACKGROUND/AIMS: The pathogenesis of Lumbar disc degeneration (LDD) has been
      extensively studied in the past. In particular, a role of matrix
      metalloproteinase 3 (MMP3) in the disease initiation and progression has been
      recently reported. However, an involvement of Insulin-like growth factor 1 (IGF
      I)-stimulated phosphatidylinositol-3 kinase (PI3k) / Akt signaling pathway
      mediated control of MMP3 in LDD has not been acknowledged. METHODS: We examined
      the serum IGF-1 levels and activation of the receptor for IGF-1 (IGF-1R) in
      resected discs in patients with LDD, compared to the fractured discs from
      traumatized, non-LDD subjects as a control. We analyzed the effects of IGF-1 on
      the activation of IGF-1R, Akt and MMP3 in a human nucleus pulposus SV40 cell line
      (HNPSV). We transfected HNPSV cells with a constitutive nuclear FoxO1, and
      analyzed its effect on the activation of IGF-1R, Akt and MMP3. RESULTS: LDD
      patients had significantly lower levels of serum IGF-1, and LDD discs had
      significantly lower levels of activated IGF-1R. IGF-1 induced phosphorylation of
      IGF-1R, and then phosphorylation of its downstream factor Akt in the HNPSV cells,
      resulting in significantly inhibition of MMP3. Further, FoxO1 nuclear retention
      completely abolished the inhibitory effects of IGF-1 on MMP3 in HNPSV cells.
      CONCLUSION: Together, IGF-1/Akt/FoxO1/MMP3 regulatory machinery may control the
      development of LDD.

PMID- 26302721
TI  - Thyroid-Stimulating Hormone Increases HNF-4alpha Phosphorylation via cAMP/PKA
      Pathway in the Liver.
AB  - Hepatocyte nuclear factor-4 alpha (HNF-4alpha) is an orphan nuclear receptor with
      important roles in hepatic metabolism. Protein phosphorylation plays a functional
      role in its nuclear localization, DNA binding, and transactivation. Thyroid
      stimulating hormone (TSH) is a hormone produced by the anterior pituitary gland,
      whose direct effect on the metabolic pathway has been observed. Our previous
      study demonstrated that TSH significantly decreases hepatic nuclear HNF-4alpha
      expression. However, whether TSH can influence HNF-4alpha phosphorylation is
      unclear. Here, we discovered that TSH can increase HNF-4alpha phosphorylation and
      modulate its subcellularlocalization. When HepG2 cells were treated with TSH, the
      phosphorylation of HNF-4alpha increased and its nuclear localization was
      interrupted. Cytoplasmic HNF-4alpha increased, while nuclear HNF-4alpha
      decreased. When the cAMP/PKA pathway was inhibited by the PKA inhibitor H89 and
      the adenylate cyclase (AC) inhibitor SQ22536, the TSH-mediated phosphorylation of
      HNF-4alpha was disrupted. When Tshr was silenced in mice, the phosphorylation of
      HNF-4alpha decreased, and cytoplasmic HNF-4alpha decreased while nuclear HNF
      4alpha increased. In conclusion, our study revealed a novel mechanism by which
      TSH regulated the hepatic HNF-4alpha subcellular localization, suggesting the
      possibility that one of the effects of TSH is to reduce the expression of HNF
      4alpha target genes. 

PMID- 26302722
TI  - In Vitro Conditioned Bone Marrow-Derived Mesenchymal Stem Cells Promote De Novo
      Functional Enteric Nerve Regeneration, but Not Through Direct
      Transdifferentiation.
AB  - Injury or neurodegenerative disorders of the enteric nervous system (ENS) cause
      gastrointestinal dysfunctions for which there is no effective therapy. This
      study, using the benzalkonium chloride-induced rat gastric denervation model,
      aimed to determine whether transplantation of bone marrow-derived mesenchymal
      stem cells (BMSC) could promote ENS neuron regeneration and if so, to elucidate
      the mechanism. Fluorescently labeled BMSC, isolated from either WT (BMSC labeled
      with bis-benzimide [BBM]) or green fluorescent protein (GFP)-transgenic rats,
      were preconditioned in vitro using fetal gut culture media containing glial cell
      derived neurotrophic factor (GDNF), and transplanted subserosally into the
      denervated area of rat pylorus. In the nerve-ablated pylorus, grafted BMSC
      survived and migrated from the subserosa to the submucosa 28 days after
      transplantation, without apparent dedifferentiation. A massive number of
      PGP9.5/NSE/HuC/D/Tuj1-positive (but GFP- and BBM-negative) neurons were
      effectively regenerated in denervated pylorus grafted with preconditioned BMSC,
      suggesting that they were regenerated de novo, not originating from trans
      differentiation of the transplanted BMSC. BMSC transplantation restored both
      basal pyloric contractility and electric field stimulation-induced relaxation.
      High levels of GDNF were induced in both in vitro-preconditioned BMSC as well as
      the previously denervated pylorus after transplantation of preconditioned BMSC.
      Thus, a BMSC-initiated GDNF-positive feedback mechanism is suggested to promote
      neuron regeneration and growth. In summary, we have demonstrated that
      allogeneically transplanted preconditioned BMSC initiate de novo regeneration of
      gastric neuronal cells/structures that in turn restore gastric contractility in
      pylorus-denervated rats. These neuronal structures did not originate from the
      grafted BMSC. Our data suggest that preconditioned allogeneic BMSC may have
      therapeutic value in treating enteric nerve disorders.

PMID- 26302723
TI  - Robust ultrasound probe tracking: initial clinical experiences during robot
      assisted partial nephrectomy.
AB  - PURPOSE: In order to assist in the identification of renal vasculature and tumour
      boundaries in robot-assisted partial nephrectomy, robust ultrasound probe
      calibration and tracking methods are introduced. Contemporaneous image guidance
      during these crucial stages of the procedure should ultimately lead to improved
      safety and quality of outcome for the patient, through reduced positive margin
      rates, segmental clamping, shorter ischaemic times and nephron-sparing resection.
      METHODS: Small KeyDot markers with circular dot patterns are attached to a
      miniature pickup ultrasound probe. Generic probe calibration is superseded by a
      more robust scheme based on a sequence of physical transducer measurements.
      Motion prediction combined with a reduced region-of-interest in the endoscopic
      video feed facilitates real-time tracking and registration performance at full HD
      resolutions. RESULTS: Quantitative analysis confirms that circular dot patterns
      result in an improved translational and rotational working envelope, in
      comparison with the previous chessboard pattern implementation. Furthermore,
      increased robustness is observed with respect to prevailing illumination levels
      and out-of-focus images due to relatively small endoscopic depths of field.
      CONCLUSION: Circular dot patterns should be employed in this context as they
      result in improved performance and robustness. This facilitates clinical usage
      and interpretation of the combined video and ultrasound overlay. The efficacy of
      the overall system is demonstrated in the first human clinical case.

PMID- 26302724
TI  - IMAGING DIAGNOSIS - USE OF MULTIPHASE COMPUTED TOMOGRAPHIC UROGRAPHY IN THE
      DIAGNOSIS OF URETERAL TEAR IN A 6-DAY-OLD FOAL.
AB  - A 6-day-old foal was evaluated for depression and inappetence. After initial
      stabilization, the filly developed a hypochloremic metabolic alkalosis and
      persistent hypercreatinemia. Abdominal ultrasound revealed fluid accumulation
      around the left kidney and a well-defined rounded fluid filled structure dorsal
      to the urinary bladder. Computed tomography revealed a partial tear of the left
      ureter with distension of the retroperitoneal membrane. Exploratory celiotomy was
      performed to allow left kidney nephrectomy. At 6 months follow-up, the filly was
      growing normally without complications. Ultrasound and CT imaging in this case
      provided an accurate diagnosis and a presurgical aid to select the appropriate
      therapeutic approach. 

PMID- 26302725
TI  - Ameliorative effect of polydatin on oxidative stress-mediated testicular damage
      by chronic arsenic exposure in rats.
AB  - Arsenic causes lipid peroxidation leading to alterations in antioxidant status in
      organisms. In this study, the reproductive effects of chronic exposure to arsenic
      and the protective effects of polydatin (PD) were evaluated in 35 Wistar male
      rats, which were divided equally into five groups. The control group received a
      normal diet and tap water, arsenic (100 mg l(-1) , approximately 1/50 of oral
      LD50 ) was given via drinking water to experimental groups except control group,
      and PD was orally given to the other groups at dose of 50, 100 and 200 mg kg(-1)
      for 60 days. Arsenic administration decreased sperm motility, glutathione level,
      superoxide dismutase and catalase activities in testicular tissue of rats. In
      contrast, malondialdehyde level and DNA damage were found to be high levels in
      arsenic-treated group. Histopathologically, it was observed that decreased sperm
      concentration and degeneration of Sertoli cells in testicular tissue. PD
      administration, partially 200 mg kg(-1) , reversed arsenic-induced lipid
      peroxidation, DNA damage, antioxidant enzyme activity and cell integrity in
      testis of rats. These results demonstrate that PD decreases arsenic-induced lipid
      peroxidation, enhances the antioxidant defence mechanism and regenerates tissue
      damage in testis of rats. 

PMID- 26302726
TI  - Erratum.

PMID- 26302727
TI  - Commentary on gender differences in prevalence, treatment, and quality of life of
      patients with chronic rhinosinusitis.
AB  - OBJECTIVE: To examine the existing evidence on gender differences in the
      prevalence, treatment, and quality of life of patients with chronic
      rhinosinusitis (CRS). METHODS: Review of the literature and expert opinion.
      RESULTS: From a sociologic standpoint, women have historically been considered
      more likely to report symptoms, seek medical care, and give poorer self
      evaluation of health, which may bias data toward increased prevalence and a
      greater effect of CRS on quality of life in women. However, the influence of
      gender seems to be restricted primarily to the evaluation of general quality of
      life, whereas the disease-specific health-related quality of life is not
      different between genders. Furthermore, migraine headaches, which are more common
      among women, may be misdiagnosed as CRS, which contributes to gender differences
      in the prevalence of CRS. The degree to which reported differences in prevalence
      and health utilization represent biologic or physiologic differences between
      genders is not known; however, differences in anatomic size, tobacco
      susceptibility, and hormonal factors have been speculated to increase the overall
      susceptibility to CRS in women compared with men. CONCLUSIONS: Focused research
      that examines the effect of gender on the development, treatment, and outcomes of
      CRS is warranted.

PMID- 26302728
TI  - Assessment of allergen-induced respiratory hyperresponsiveness before the
      prescription of a specific immunotherapy.
AB  - BACKGROUND: Asymptomatic sensitization is a frequent condition that must be
      considered before the indication of allergic-specific immunotherapy. OBJECTIVE:
      The aim of this study was to appreciate and correlate the local and spirometric
      changes elicited by the allergen-specific nasal provocation test (NPT) to define
      practical and feasible guidelines for the allergist/immunologist to demonstrate
      specific respiratory hyperresponsiveness before the indication of allergic
      specific immunotherapy. METHODS: A total of 172 subjects (children and adults)
      with a diagnosis of allergic rhinitis were submitted to flow-volume spirometry
      immediately before and after the NPT performed with Dermatophagoides antigens.
      The differences between the pre- and postspirometric estimated values of peak
      expiratory flow rate (PEFdif%), forced expiratory volume in 1 second (FEV1dif%),
      and forced vital capacity (FVCdif%) were correlated with the results of the nasal
      provocation test symptom score (NPT-SS). RESULTS: There were 119 subjects (69%)
      with NPT-SS > 2. Among these patients who were reactive, the mean NPT-SS was 6.3.
      The Spearman's correlation between PEFdif% and NPT-SS was r = -0.44 (p = 0.01);
      the Spearman's correlation between FEV1dif% and NPT-SS was r = -0.22 (p = 0.01),
      and the Spearman's correlation between FVCdif% and NPT-SS was r = -0.21 (p =
      0.04). CONCLUSION: The combined utilization of the allergen-specific NPT-SS with
      the spirometry (or PEF meter) is a safe methodology to evaluate allergen-specific
      nasal and bronchial hyperresponsiveness (which sometimes acts as a bronchial
      provocation test) in patients with allergic rhinitis and asthma due to
      hypersensitivity who are candidates for allergen-specific immunotherapy.

PMID- 26302729
TI  - Nasal histamine responses in nonallergic rhinitis with eosinophilic syndrome.
AB  - BACKGROUND: Nonallergic rhinitis with eosinophilic syndrome (NARES) is
      persistent, without atopy, but with >=25% nasal eosinophilia. Hypereosinophilia
      seems to contribute to nasal mucosa dysfunction. OBJECTIVES: This analytical case
      control study aimed at assessing the presence and severity of nonspecific nasal
      hyperactivity and at finding out whether eosinophilia may be correlated with the
      respiratory and mucociliary clearance functions. MATERIALS: The symptom score was
      assessed in 38 patients and 15 controls whose nasal smear was also tested for
      eosinophils and mucociliary transport (MCT). Nonspecific nasal provocation tests
      (NSNPT) with histamine were also carried out, and total nasal resistance (TNR)
      was determined. RESULTS: The symptom score of NARES after NSNPT were not
      significantly different from the control group, and there was poor or no
      correlation among the single symptoms and the differences studied for every nasal
      reactivity class. This correlation improved when using the composite symptom
      score. The most severe eosinophilia was observed in high reactivity groups, and
      it was correlated with an increase in TNR. MCT worsened as eosinophilia and nasal
      reactivity increased. Unlike controls, a significant correlation was observed
      between the increase in MCT and TNR. CONCLUSIONS: In NARES, nonspecific nasal
      hyperreactivity is the result of epithelial damage produced by eosinophilic
      inflammation, which causes MCT slow down, an increase in TNR, and nasal
      reactivity classes, with possible impact on classification, prognosis, and
      treatment control.

PMID- 26302730
TI  - Gene expression profiles in chronic idiopathic (spontaneous) urticaria.
AB  - BACKGROUND: The pathophysiology of chronic idiopathic (spontaneous) urticaria
      (CIU) is poorly understood. OBJECTIVE: We hypothesized that a study of gene
      expression in active lesions from patients with CIU would uncover unexpected
      associations. METHODS: We enrolled eight patients with CIU and six healthy
      controls, and obtained 4 mm punch biopsy specimens of active lesions and
      unaffected skin of patients with CIU and of skin from normal controls. Routine
      histologic evaluation was performed, RNA was isolated, and gene expression data
      were assessed. Due to technical reasons, the final evaluation included six
      samples of lesional skin, six samples of nonlesional skin, and five samples of
      normal skin. RESULTS: As expected, lesional skin had more inflammatory cells per
      high-powered field (mean +/- SE, 96 +/- 6) than did samples from nonlesional skin
      of the subjects with CIU (17 +/- 2) (p < 0.01). Lesions of CIU showed significant
      upregulation of 506 genes and reduced expression of 51 genes. Those most
      upregulated were predominantly involved in cell adhesion (e.g., selectin E
      [SELE]), cell activation (e.g., CD69), and chemotaxis (e.g., CCL2). Twelve
      independent canonical pathways with p <= 0.001 were identified (including
      intracellular kinase pathways (RAs-related nuclear protein [RAN] and Janus
      activated kinase/interferon), cytokine signaling pathways (IL-9, IL10, and IFN),
      a strong inflammatory response (interferon, IL-9, IL-10, inducible nitric oxide
      synthase and glucocorticoid pathways) and increased cell proliferation (RAN
      signaling, cell cycle control, and tRNA charging). CONCLUSIONS: This preliminary
      study describes a method to study gene activation in urticarial lesions and
      demonstrated a strong inflammatory response with a large variety of activated
      genes that are distinct from those reported with other dermatologic conditions.

PMID- 26302731
TI  - Association of IL13R alpha 1 +1398A/G polymorphism in a North Indian population
      with asthma: A case-control study.
AB  - BACKGROUND: Interleukin 13 (IL13) is directly involved in the secretion of total
      serum immunoglobulin E (IgE), which plays a major role in the asthma
      pathogenesis. OBJECTIVE: One of the polymorphic receptor of IL13 is IL13Ralpha1,
      which after binding to IL13, initiates signal transduction that results in mucin
      secretion, airway hyperreactivity, fibrosis, and chitinase up-regulation, which
      increases asthma risk. METHODS: In the present study, the role of IL13Ralpha1
      +1398A/G gene polymorphisms in asthma was detected with a total of 964
      individuals, including 483 healthy controls and 481 asthma patients from a North
      Indian population using polymerase chain reaction-restriction fragment length
      polymorphism method. RESULTS: Statistical analysis revealed that the mutant
      allele (G) is predominant in asthma patients (42.7%) than the controls (38.2%),
      which shows an increased risk toward asthma with odds ratio = 1.21, 95%
      confidence interval (1.00-1.45), chi(2) = 4.10 and p = 0.043. Furthermore, the
      phenotypic characteristics also reveal a significant association with the disease
      (p < 0.05). CONCLUSIONS: This is the first study conducted in India and +1398A/G
      polymorphism in noncoding region of IL13Ralpha1 confer risk toward asthma in the
      studied population.

PMID- 26302732
TI  - Bioabsorbable steroid-releasing sinus implants in the frontal and maxillary
      sinuses: 2-year follow-up.
AB  - BACKGROUND: Mometasone furoate-releasing implants have been approved for use in
      the ethmoid sinuses following endoscopic sinus surgery (ESS) to reduce the need
      for medical and surgical intervention postoperatively. Outcomes have not yet been
      studied when these implants are utilized in other paranasal sinuses after ESS.
      OBJECTIVE: To present a case in which bioabsorbable steroid-eluting implants were
      used to maintain patency and to decrease inflammation in the frontal and
      maxillary sinuses after revision ESS. METHODS: 52-year-old male with lifelong
      allergic rhinitis, chronic allergic fungal rhinosinusitis, and inflammatory bowel
      disease had previously undergone four endoscopic sinus surgeries, subcutaneous
      injection immunotherapy, and topical therapy with budesonide and amphotericin
      sinus irrigations. In July, 2012, during revision left frontal sinusotomy and
      right maxillary antrostomy (the fifth ESS), two bioabsorbable steroid-releasing
      implants were placed in the left frontal recess and the right maxillary sinus
      respectively and followed clinically, endoscopically, and radiographically for
      two years. RESULTS: Two year followup demonstrated near complete clinical,
      endoscopic, and radiographic resolution of the patient's signs and symptoms of
      chronic rhinosinusitis. CONCLUSIONS: The steroid-releasing implants during the
      critical phase of wound-healing appear to have allowed the patient, now over two
      years postoperatively, to achieve a healthier state and to allow more successful
      management than the preceding 15-20 years.

PMID- 26302733
TI  - Nasal septal perforation associated with pyoderma gangrenosum.
AB  - BACKGROUND: Pyoderma gangrenosum (PG) is a skin condition characterized by
      necrotic ulcers and most commonly occurs on the legs in association with
      inflammatory bowel disease and rheumatoid arthritis; however, PG rarely involves
      the head and neck, and very rarely causes nasal septal perforation. OBJECTIVE:
      Here, we describe a case report of PG causing nasal septal perforation in a 71
      year-old male with truncal lesions in the absence of either inflammatory bowel
      disease or autoimmune arthritis. METHODS: Case report with histologic
      description. RESULTS: Histology from nasal mucosal biopsies showed chronic
      inflammation and reactive change without evidence of malignancy. Together with
      serologic and nonserologic testing, as well as clinical evaluation, we were able
      to rule out other causes of septal perforation including Wegener's
      granulomatosis, lymphoma, and vasculitis, and concluded that the cause of nasal
      septal perforation was most likely PG. CONCLUSION: Septal perforation etiology
      should include a complete history and physical to evaluate for systemic
      etiologies, including rare ones such as PG.

PMID- 26302734
TI  - Successful endoscopic endonasal repair of nasal meningoencephalocele in a 21-day
      old neonate.
AB  - INTRODUCTION: Indications of surgical intervention in congenital nasal
      meningoencephaloceles includes presence of cerebro spinal fluid rhinorrhea having
      a risk of causing meningitis, episodes of prior meningitis and bilateral nasal
      obstruction causing respiratory difficulty in these obligate nasal breathers.
      Many authors would like to wait till the patient attains the age of 2 to 3 years
      for repair of the defect due to surgical feasibility. However, early intervention
      prevents further episodes of meningitis in the future. We present the youngest
      patient of nasal meningoencephalocele successfully repaired via endoscopic
      approach. CASE REPORT: A 21 days old neonate was referred to us with a nasal
      meningoencephalocele with active cerebrospinal fluid rhinorrhoea. Radiological
      investigation showed a cribriform plate defect on the right side. Repair was done
      by endoscopic route by multi-layered closure of the defect which was augmented
      with a mucoperichondrial flap from the septum. Patient was asymptomatic in the
      post-operative follow up period and did not have any episode of meningitis till
      date. CONCLUSION: Early repair by transnasal endoscopic route is a feasible
      surgical option for congenital anterior skull base defects with
      meningoencephaloceles to prevent further episodes of meningitis. This is feasible
      even in the neonatal period due to improved technique and instrumentation now
      available for endoscopic nasal surgeries.

PMID- 26302735
TI  - Ethmoid pneumocele presenting with exophthalmos 15 years after endoscopic sinus
      surgery.
AB  - INTRODUCTION: A pneumocele is an abnormal dilation of an air-containing sinus
      beyond the normal margins of bone, with associated bony thinning. A delayed
      ethmoid pneumocele after sinus surgery has not previously been reported. METHODS:
      A case report of a patient with a delayed ethmoid pneumocele after sinus surgery.
      The diagnostic workup, operative approach, and postoperative results were
      evaluated. RESULTS: A 57-year-old female with a history of endoscopic sinus
      surgery 15 years prior presented with right eye proptosis and severe orbital and
      facial pressure. A maxillofacial computed tomography showed a markedly expanded
      air-filled right anterior ethmoid space with a dehiscent lamina papyracea,
      consistent with a pneumocele. Marsupialization of the pneumocele as well as a
      revision ethmoidectomy were performed, with a visible return of the orbital
      contents to a more natural position. The patient experienced worsened diplopia
      immediately postoperatively that resolved within two weeks. CONCLUSIONS: This
      case demonstrates that a pneumocele can present even years after endoscopic sinus
      surgery, and acute but temporary development or worsening of diplopia can result
      from surgical decompression of the pneumocele as the eye returns to its natural
      position.

PMID- 26302736
TI  - Nasal epithelial myoepithelial carcinoma: An unusual cause of epiphora, a case
      report and review of the literature.
AB  - INTRODUCTION: Epithelial myoepithelial carcinoma (EMC) of the nasal cavity is a
      rare tumor, and here we describe the first case of EMC of the nasal cavity
      presenting with epiphora. A case presentation and review of the literature is
      provided. METHODS: A case report is described of a 63-year-old man who presented
      with unilateral epiphora and was found via a thorough history and physical
      examination to have a nasal tumor. The physical examination consisted of an
      ocular examination, including probing and irrigation, and a detailed nasal
      examination (anterior rhinoscopy, nasal endoscopy). The nasal examination was
      prompted by the patient's report of concurrent nasal symptoms during history
      taking. Immunohistochemistry subsequently identified the nasal tumor as EMC. A
      literature search was performed to gain insights into similar malignancies of the
      nasal cavity. RESULTS: Eight cases of EMC of the nasal cavity were identified in
      the literature, none of the patients presented with epiphora. The case presented
      here resulted in resolution of the patient's symptoms and no evidence of disease
      after surgical excision. CONCLUSION: Epithelial myoepithelial is a rare salivary
      gland malignancy that can arise in the nasal cavity. Unilateral epiphora with
      concurrent nasal symptoms should prompt nasal cavity examination for the
      possibility of an obstructive tumor.

PMID- 26302737
TI  - Bilateral meningoencephaloceles with cerebrospinal fluid rhinorrhea after facial
      advancement in the Crouzon syndrome.
AB  - BACKGROUND: Cerebrospinal fluid (CSF) rhinorrhea and encephaloceles are rare
      complications of craniofacial advancement procedures performed in patients with
      craniofacial dysostoses (CD) to address the ramifications of their midface
      hypoplasia including obstructed nasal airway, exorbitism, and impaired
      mastication. Surgical repair of this CSF rhinorrhea is complicated by occult
      elevations in intracranial pressure (ICP), potentially necessitating open,
      transcranial repair. We report the first case in otolaryngology literature of a
      patient with Crouzon syndrome with late CSF rhinorrhea and encephalocele
      formation after previous LeFort III facial advancement surgery. OBJECTIVES:
      Describe the case of a patient with Crouzon syndrome who presented with CSF
      rhinorrhea and encephaloceles as complications of Le Fort III facial advancement
      surgery. Review the literature pertaining to the incidence and management of post
      operative CSF rhinorrhea and encephaloceles. Analyze issues related to repair of
      these complications, including occult elevations in ICP, the utility of
      perioperative CSF shunts, and the importance of considering alternative repair
      schemes to the traditional endonasal, endoscopic approach. METHODS: Review of the
      literature describing CSF rhinorrhea and encephalocele formation following facial
      advancement in CD, focusing on management strategies. RESULTS: CSF rhinorrhea and
      encephalocele formation are rare complications of craniofacial advancement
      procedures. Occult elevations in ICP complicate the prospect of permanent
      surgical repair, potentially necessitating transcranial repair and the use of CSF
      shunts. Though no consensus exists regarding the utility of perioperative CSF
      drains, strong associations exist between elevated ICP and failed surgical
      repair. Additionally, the anatomic changes in the frontal and ethmoid sinuses
      after facial advancement present a challenge to endoscopic repair. CONCLUSION:
      Otolaryngologists should be aware of the possibility of occult elevations in ICP
      and sinonasal anatomic abnormalities when repairing CSF rhinorrhea in patients
      with CD. Clinicians should consider CSF shunt placement and carefully weigh the
      advantages of the transcranial approach versus endonasal, endoscopic techniques.

PMID- 26302738
TI  - Steroid sparing effect of omalizumab in seropositive allergic bronchopulmonary
      aspergillosis.
AB  - BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is a common serious
      hypersensitivity reaction to airway colonization with Aspergillus in patients
      with asthma or cystic fibrosis. While steroids are effective in controlling the
      respiratory symptoms of ABPA, they have many side effects that make them
      undesirable for long term use. Antifungals have been used to reduce dependency on
      systemic steroids but long term use can be limited by side effects and there is
      the possibility of developing resistance to azoles. Some clinicians have
      successfully used anti-immunoglobulin E (anti-IgE) therapy in various
      populations, though it is frequently added to antifungals. OBJECTIVE: Further
      describe the utility of anti-IgE therapy for ABPA for patients unable to tolerate
      antifungals. METHODS: We describe the case of a patient with serologic ABPA who
      did not tolerate therapy with antifungals but was able to significantly reduce
      her average daily steroid use while receiving anti-IgE therapy with omalizumab
      added to her other respiratory medications. RESULTS: After therapy with
      omalizumab, our patient was able to reduce her need for daily corticosteroids by
      nearly 80%. CONCLUSIONS: Omalizumab may reduce corticosteroid dependence in
      patients with allergic bronchopulmonary aspergillosis for patients unable to
      tolerate antifungals, though use may be limited by cost. Additional studies are
      needed. <ext-link ext-link-type="uri" xmlns:xlink="http://www.w3.org/1999/xlink"
      xlink:href="ClinicalTrial.gov">ClinicalTrial.gov</ext-link> identifier
      NCT00787917.

PMID- 26302739
TI  - Fine-needle aspiration cytology in a rare case of recurrent mucinous carcinoma of
      skin, displaying psammoma bodies on smears.
AB  - Primary mucinous carcinoma of skin is an uncommonly documented tumor, especially
      on fine-needle aspiration cytology (FNAC) smears. A 58-year-old gentleman
      presented with a recurrent swelling over his right zygoma. Earlier, he had
      undergone surgical resection at the same site, on two occasions, 4 years back.
      FNAC smears from the recurrent nodule displayed clusters and singly scattered
      relatively monomorphic, polygonal to plasmacytoid cells with mild nuclear atypia
      and moderate to abundant cytoplasm, including focal intracytoplasmic vacuoles. At
      places, tumor cells were arranged around psammoma bodies against a background of
      mucinous material. Histopathological sections from the subsequent tumor resection
      revealed tumor cells arranged in the form of islands, nests, cribriform, and
      papillary arrangements amidst mucinous stroma, along with focal psammomatous
      calcification, consistent with a recurrent mucinous adenocarcinoma. On
      immunohistochemistry, tumor cells were diffusely positive for CK 7, estrogen
      receptor (ER), and progesterone receptor (PR), while negative for CDX2, CK20, and
      TTF1. Diagnosis of a recurrent mucinous carcinoma of skin was offered. Patient
      underwent adjuvant radiotherapy for achieving better loco regional clearance and
      is disease-free, 4 months after. FNAC is a useful diagnostic tool for timely
      identification of mucinous carcinoma of skin, including recurrent lesions.
      Psammomatous calcification can be identified within this uncommon tumor, in
      recurrent lesions. While surgical resection remains the treatment mainstay,
      immunohistochemical expression of ER and PR in this tumor perhaps could have
      therapeutic impact, especially in recurrent cases.

PMID- 26302741
TI  - Spatial Frames of Reference in Traditional Negev Arabic: Language-to-Cognition
      Correlation.
AB  - Linguistic and cognitive tasks on spatial Frames of Reference (FoRs) in
      Traditional Negev Arabic (TNA) show that TNA is a referentially promiscuous
      language, using Intrinsic, Relative and Absolute FoRs. FoRs are selected in
      context according to culture-specific features of the ground (G). TNA speakers
      exclusively use the Absolute FoR in cognitive tasks, similarly to Mesoamerican
      languages (Bohnemeyer et al. in Proceedings of the 36th Annual Conference of the
      Cognitive Science Society, Austin, 2014). Absolute FoR in TNA is anchored on the
      four cardinal directions. Nevertheless, in TNA and in other varieties of Nomadic
      Arabic, geocentric sub-types of the Absolute FoR are also observable. Indeed, as
      in other Absolute-framing systems worldwide, different anchoring strategies
      (geocentric and astronomic) tend to coexist. I define their coexistence "Absolute
      Referential Modularity" (ARM). ARM appears in TNA in cognitive referential tasks
      and in some lexical items, not in linguistic tasks (as elaborated by Levinson et
      al. in Space stimuli kit 1.2: November 1992. Max Planck Institute for
      Psycholinguistics, Nijmegen, pp 7-14, 1992). Cardinal directions across Nomadic
      Arabic varieties show great cultural salience. They are associated with concrete
      geographical elements and encode topological relations: east-west axis encodes
      the mountain-sea opposition, beside many symbolic meanings, and encodes the
      oppositions Up/Down and Inside (familiar)/Outside (foreign). The detection of
      cognitive and linguistic Absolute referential practices-characterized by
      Modularity-and the cultural salience of cardinal directions within the whole
      Nomadic Arabic linguistic group, support the bias for Absolute cognition in
      promiscuous systems and its antecedence with respect to later linguistic
      referential strategies (Bohnemeyer et al. 2014). TNA linguistic promiscuity
      represents an innovation with respect to the cognitive concepts and demonstrates
      that language first generates semantic structures, which may later influence
      cognitive representations. Nevertheless, in TNA the independence of linguistic
      and cognitive spatial representations is hard to deny.

PMID- 26302740
TI  - Catheter ablation for atrial fibrillation in hypertrophic cardiomyopathy
      patients: a systematic review.
AB  - PURPOSE: The primary aim of this systematic review was to assess the efficacy of
      catheter ablation of atrial fibrillation (AF) in patients with hypertrophic
      cardiomyopathy (HCM). Differentiation based off catheter ablation modalities was
      not considered due to the limited scope of the current field. Studies that
      employed alcohol septal ablation for the treatment of AF in HCM patients were
      excluded as were abstracts, case reports, conference presentations, editorials,
      reviews, and expert opinions METHODS: Electronic searches were performed in six
      databases from their inception until January 2014. Relevant studies regarding
      catheter ablation for AF in HCM populations were identified. Data was extracted
      and analyzed according to pre-defined clinical endpoints RESULTS: A review was
      undertaken of eight studies in which 241 HCM patients underwent catheter ablation
      for AF. Overall AF-free survival at last follow-up ranged from 47 to 77% (64
      67%). Sinus rhythm was maintained at last follow-up in 47-82% (median 64-67%). AF
      recurrence ranged from 0 to 66% (median 35-40%). CONCLUSION: A review of the
      current evidence suggests that catheter ablation of AF in HCM patients is
      effective with suitable efficacy and is justified in select patients. Future
      adequately powered randomized studies should be undertaken aimed at addressing
      long-term efficacy and complications associated with procedural outcomes.

PMID- 26302742
TI  - Transcriptome profile analysis reflects rat liver and kidney damage following
      chronic ultra-low dose Roundup exposure.
AB  - BACKGROUND: Glyphosate-based herbicides (GBH) are the major pesticides used
      worldwide. Converging evidence suggests that GBH, such as Roundup, pose a
      particular health risk to liver and kidneys although low environmentally relevant
      doses have not been examined. To address this issue, a 2-year study in rats
      administering 0.1 ppb Roundup (50 ng/L glyphosate equivalent) via drinking water
      (giving a daily intake of 4 ng/kg bw/day of glyphosate) was conducted. A marked
      increased incidence of anatomorphological and blood/urine biochemical changes was
      indicative of liver and kidney structure and functional pathology. In order to
      confirm these findings we have conducted a transcriptome microarray analysis of
      the liver and kidneys from these same animals. RESULTS: The expression of 4224
      and 4447 transcript clusters (a group of probes corresponding to a known or
      putative gene) were found to be altered respectively in liver and kidney (p <
      0.01, q < 0.08). Changes in gene expression varied from -3.5 to 3.7 fold in liver
      and from -4.3 to 5.3 in kidneys. Among the 1319 transcript clusters whose
      expression was altered in both tissues, ontological enrichment in 3 functional
      categories among 868 genes were found. First, genes involved in mRNA splicing and
      small nucleolar RNA were mostly upregulated, suggesting disruption of normal
      spliceosome activity. Electron microscopic analysis of hepatocytes confirmed
      nucleolar structural disruption. Second, genes controlling chromatin structure
      (especially histone-lysine N-methyltransferases) were mostly upregulated. Third,
      genes related to respiratory chain complex I and the tricarboxylic acid cycle
      were mostly downregulated. Pathway analysis suggests a modulation of the mTOR and
      phosphatidylinositol signalling pathways. Gene disturbances associated with the
      chronic administration of ultra-low dose Roundup reflect a liver and kidney
      lipotoxic condition and increased cellular growth that may be linked with
      regeneration in response to toxic effects causing damage to tissues. Observed
      alterations in gene expression were consistent with fibrosis, necrosis,
      phospholipidosis, mitochondrial membrane dysfunction and ischemia, which
      correlate with and thus confirm observations of pathology made at an anatomical,
      histological and biochemical level. CONCLUSION: Our results suggest that chronic
      exposure to a GBH in an established laboratory animal toxicity model system at an
      ultra-low, environmental dose can result in liver and kidney damage with
      potential significant health implications for animal and human populations.

PMID- 26302743
TI  - Genome-wide identification, phylogeny and expression analysis of GRAS gene family
      in tomato.
AB  - BACKGROUND: GRAS transcription factors usually act as integrators of multiple
      growth regulatory and environmental signals, including axillary shoot meristem
      formation, root radial pattering, phytohormones, light signaling, and
      abiotic/biotic stress. However, little is known about this gene family in tomato
      (Solanum lycopersicum), the most important model plant for crop species with
      fleshy fruits. RESULTS: In this study, 53 GRAS genes were identified and renamed
      based on tomato whole-genome sequence and their respective chromosome
      distribution except 19 members were kept as their already existed name. Multiple
      sequence alignment showed typical GRAS domain in these proteins. Phylogenetic
      analysis of GRAS proteins from tomato, Arabidopsis, Populus, P.mume, and Rice
      revealed that SlGRAS proteins could be divided into at least 13 subfamilies.
      SlGRAS24 and SlGRAS40 were identified as target genes of miR171 using5'-RACE
      (Rapid amplification of cDNA ends). qRT-PCR analysis revealed tissue-/organ- and
      development stage-specific expression patterns of SlGRAS genes. Moreover, their
      expression patterns in response to different hormone and abiotic stress
      treatments were also investigated. CONCLUSIONS: This study provides the first
      comprehensive analysis of GRAS gene family in the tomato genome. The data will
      undoubtedly be useful for better understanding the potential functions of GRAS
      genes, and their possible roles in mediating hormone cross-talk and abiotic
      stress in tomato as well as in some other relative species.

PMID- 26302745
TI  - Cross-sectional longitudinal study of the academic half-day format in a
      hematology-oncology fellowship training program.
AB  - BACKGROUND: Few published studies have evaluated the effectiveness of changing
      the traditional curriculum of several hourly educational sessions per week to an
      academic half-day (AHD) educational format. This study describes our experience
      with implementing an AHD format in the Hematology-Oncology Fellowship Program at
      The University of Texas MD Anderson Cancer Center and evaluates the perceptions
      that learners had for this format. METHODS: Using a mixed quantitative and
      qualitative approach, we evaluated our AHD program using four yearly fellows'
      surveys to assess the Hematology-Oncology Fellows' perceptions of the
      effectiveness of the AHD format. We analyzed the fellows' perceptions using
      descriptive statistics and thematic analysis of the qualitative data collected
      from the surveys. We used a quality improvement approach by implementing and
      testing changes to the AHD over 4 years on the basis of the data collected from
      the yearly fellows' surveys. We also collected third-year fellows' Oncology In
      Training Exam (ITE) scores from 2008 to 2014. RESULTS: We found that the fellows
      perceived the AHD format favorably; fellows agreed that they had more motivation
      to attend AHD, more concentration during the sessions, more effective weekly work
      organization, and increased knowledge retention. We established the reliability
      of our survey tool (Cronbach's alpha = 0.83) as well as content and construct
      validity. We saw an increasing trend in ITE scores since the AHD was implemented.
      CONCLUSIONS: Our results contribute to further understanding the effect of the
      AHD format on trainees. Using a continuous evaluation and an educational quality
      improvement strategy, we found that the AHD curriculum was associated with a
      rising trend in learners' exam scores and increased learner satisfaction.

PMID- 26302746
TI  - A New Scoring Function for Molecular Docking Based on AutoDock and AutoDock Vina.
AB  - Molecular docking of small molecules in the protein binding sites is the most
      widely used computational technique in modern structure-based drug discovery.
      Although accurate prediction of binding modes of small molecules can be achieved
      in most cases, estimation of their binding affinities remains mediocre at best.
      As an attempt to improve the correlation between the inhibitory constants, pKi,
      and scoring, we created a new, hybrid scoring function. The new function is a
      linear combination of the terms of the scoring functions of AutoDock and AutoDock
      Vina. It was trained on 2,412 protein-ligand complexes from the PDBbind database
      (www.pdbbind.org.cn, version 2012) and validated on a set of 313 complexes
      released in the 2013 version as a test set. The new function was included in a
      modified version of AutoDock. The hybrid scoring function showed a statistically
      significant improvement in both training and test sets in terms of correlation
      with and root mean square and mean absolute errors in prediction of pKi values.
      It was also tested on the CSAR 2014 Benchmark Exercise dataset (team T) and
      produced reasonably good results. 

PMID- 26302744
TI  - Common or distinct pathways to psychosis? A systematic review of evidence from
      prospective studies for developmental risk factors and antecedents of the
      schizophrenia spectrum disorders and affective psychoses.
AB  - BACKGROUND: Identifying the unique and shared premorbid indicators of risk for
      the schizophrenia spectrum disorders (SSD) and affective psychoses (AP) may
      refine aetiological hypotheses and inform the delivery of universal versus
      targeted preventive interventions. This systematic review synthesises the
      available evidence concerning developmental risk factors and antecedents of SSD
      and AP to identify those with the most robust support, and to highlight remaining
      evidence gaps. METHODS: A systematic search of prospective birth, population,
      high-risk, and case-control cohorts was conducted in Medline and supplemented by
      hand searching, incorporating published studies in English with full text
      available. Inclusion/exclusion decisions and data extraction were completed in
      duplicate. Exposures included three categories of risk factors and four
      categories of antecedents, with case and comparison groups defined by adult
      psychiatric diagnosis. Effect sizes and prevalence rates were extracted, where
      available, and the strength of evidence synthesised and evaluated qualitatively
      across the study designs. RESULTS: Of 1775 studies identified by the search, 127
      provided data to the review. Individuals who develop SSD experience a diversity
      of subtle premorbid developmental deficits and risk exposures, spanning the
      prenatal period through early adolescence. Those of greatest magnitude (or
      observed most consistently) included obstetric complications, maternal illness
      during pregnancy (especially infections), other maternal physical factors,
      negative family emotional environment, psychopathology and psychotic symptoms,
      and cognitive and motor dysfunctions. Relatively less evidence has accumulated to
      implicate this diversity of exposures in AP, and many yet remain unexamined, with
      the most consistent or strongest evidence to date being for obstetric
      complications, psychopathology, cognitive indicators and motor dysfunction. Among
      the few investigations affording direct comparison between SSD and AP, larger
      effect sizes and a greater number of significant associations are commonly
      reported for SSD relative to AP. CONCLUSIONS: Shared risk factors for SSD and AP
      may include obstetric complications, childhood psychopathology, cognitive markers
      and motor dysfunction, but the capacity to distinguish common versus distinct
      risk factors/antecedents for SSD and AP is limited by the scant availability of
      prospective data for AP, and inconsistency in replication. Further studies
      considering both diagnoses concurrently are needed. Nonetheless, the prevalence
      of the risk factors/antecedents observed in cases and controls helps demarcate
      potential targets for preventative interventions for these disorders.

PMID- 26302748
TI  - A novel 5 nucleotide deletion in XPA gene is associated with severe neurological
      abnormalities.

PMID- 26302747
TI  - Knowledge, attitude, and practices towards schistosomiasis among rural population
      in Yemen.
AB  - BACKGROUND: Schistosomiasis is highly prevalent in Yemen, with an estimated 3
      million cases, particularly among rural communities. This community-based study
      aims to evaluate the knowledge, attitude and practices (KAP) on schistosomiasis
      among rural communities in Yemen. METHODS: A cross-sectional study was carried
      out among 250 households from ten rural districts in Yemen. Overall, 400 children
      were screened for urogenital and intestinal schistosomiasis. Moreover, parents
      were interviewed using a pre-tested questionnaire to collect information about
      the demographic and socioeconomic information and their KAP concerning
      schistosomiasis. RESULTS: A total of 127 (31.8%) children were found to be
      excreting schistosome eggs in either their urine or faeces (22.5% S. haematobium
      and 8.0% S. mansoni). Although 92.4% of the respondents had heard about
      schistosomiasis, 49.8%, 68.0% and 47.2% had knowledge concerning the
      transmission, signs and symptoms, and prevention, respectively. In addition,
      77.1% considered schistosomiasis as harmful while 48.5% believed that
      schistosomiasis could be prevented, albeit their practices to prevent infections
      were still inadequate. Significant associations between the KAP and age,
      education, employment status and household monthly income were reported (P <
      0.05). Moreover, a significantly higher level of knowledge was reported among the
      respondents who had infected children compared to those with no infected family
      members (P < 0.05). Multiple logistic regression analysis revealed that the level
      of education and the history of schistosomiasis were the most important factors
      associated with the KAP concerning schistosomiasis among this population.
      CONCLUSION: This study reveals that knowledge about the cause, transmission,
      symptoms and prevention of schistosomiasis among the rural population in Yemen
      was inadequate, and that this could be a challenging obstacle to the elimination
      of schistosomiasis in these communities. Besides the current mass drug
      administration, school and community-based health education regarding
      schistosomiasis is imperative among these communities to significantly reduce the
      transmission and morbidity of schistosomiasis.

PMID- 26302749
TI  - Suppression of intestinal immunity through silencing of TCTP by RNAi in
      transgenic silkworm, Bombyx mori.
AB  - Intestinal immune response is a front line of host defense. The host factors that
      participate in intestinal immunity response remain largely unknown. We recently
      reported that Translationally Controlled Tumor Protein (BmTCTP) was obtained by
      constructing a phage display cDNA library of the silkworm midgut and carrying out
      high throughput screening of pathogen binding molecules. To further address the
      function of BmTCTP in silkworm intestinal immunity, transgenic RNAi silkworms
      were constructed by microinjection piggBac plasmid to Dazao embryos. The
      antimicrobial capacity of transgenic silkworm decreased since the expression of
      gut antimicrobial peptide from transgenic silkworm was not sufficiently induced
      during oral microbial challenge. Moreover, dynamic ERK phosphorylation from
      transgenic silkworm midgut was disrupted. Taken together, the innate immunity of
      intestinal was suppressed through disruption of dynamic ERK phosphorylation after
      oral microbial infection as a result of RNAi-mediated knockdown of midgut TCTP in
      transgenic silkworm.

PMID- 26302750
TI  - Association analysis between the distributions of histone modifications and gene
      expression in the human embryonic stem cell.
AB  - It is well known that histone modifications are associated with gene expression.
      In order to further study this relationship, 16 kinds of Chip-seq histone
      modification data and mRNA-seq data of the human embryonic stem cell H1 are
      chosen. The distributions of histone modifications in the regions flanking
      transcription start sites (TSSs) for highly expressed and lowly expressed genes
      are computed, respectively. And four types of distributions of histone
      modifications in regions flanking TSSs and the spatial patterning of the
      correlations between histone modifications and gene expression are detected. Our
      results suggest that the correlations between the regions overlapped by peaks are
      higher than the non-overlapped ones for each histone modification. In addition,
      to obtain the effect of the cooperative action of histone modification on gene
      expression, five histone modification clusters are found in highly expressed and
      lowly expressed genes, histone modification and gene expression interaction
      network is constructed. To further explore which region is the main target region
      for the specific histone modification, the human genes are divided into five
      functional regions. The results indicate that histone modifications are mostly
      located in the promoters of highly expressed genes versus the exons of lowly
      expressed genes, and exons have a smaller range of normalized tag counts than
      other gene elements in the two groups of genes. Finally, the type specificity and
      regional bias of histone modifications for 11 key transcription factor genes
      regulating the stem cell renewal are analyzed. 

PMID- 26302751
TI  - The potential role of miRNAs 21 and 199-a in early diagnosis of hepatocellular
      carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is regarded as one of the most common
      malignancies and among the leading causes of cancer death among the whole world.
      The most urgent needs are to find sensitive markers for early diagnosis for HCC.
      MicroRNAs (miRNAs) are reported as a group of small non-coding RNAs that can
      function as endogenous RNA interference to regulate expression of the targeted
      genes. This study was conducted to detect the serum and tissue expression of miR
      21 and miR 199-a to be applied as early detectors for HCC. METHODS: A total of 40
      serum and tissue samples (17 samples from chronic hepatitis and 23 samples from
      HCC patients) were collected. The levels of the two mature miRNAs (miR-21 and miR
      199-a) were detected by real time quantitative reverse-transcriptase PCR (RT
      qPCR) in sera and tissues of chronic hepatitis and HCC patients. Besides, miR-21
      and miR-199-a levels in relation to clinical and pathological factors were
      explored. RESULTS: We found that the expression of serum miR-21 was distinctly
      increased in HCC compared with chronic hepatitis (P<0.001). miR 199-a was
      distinctly decreased in HCC compared with chronic hepatitis (P<0.001). In
      addition, median of miR 21 was increased in malignant when compared to adjacent
      non-malignant tissues without significant differences (P=0.191) while miR 199-a
      was significantly decreased in malignant when compared to adjacent nonmalignant
      tissues (P<0.001). ROC analysis showed that miR-21 and miR-199-a might be
      potential biomarkers for HCC. CONCLUSIONS: In conclusion, the expression of miR
      21 was significantly up-regulated and miR-199-a was significantly down regulated
      in serum of patients with HCC. Due to their reasonable sensitivity and
      specificity for disease progression, miR-21 and miR-199-a could be used as
      potential circulating biomarkers for HCC.

PMID- 26302752
TI  - In vivo expression of human cytomegalovirus (HCMV) microRNAs during latency.
AB  - Viral encoded microRNAs play key roles in regulating gene expression and the life
      cycle of human herpes viruses. Latency is one of the hallmarks of the human
      cytomegalovirus (HCMV or HHV5) life cycle, and its control may have immense
      practical applications. The present study aims to identify HCMV encoded microRNAs
      during the latency phase of the virus. We used a highly sensitive real time PCR
      (RTPCR) assay that involves a pre-amplification step before RTPCR. It can detect
      HCMV encoded microRNAs (miRNAs) during latency in purified monocytes and PBMCs
      from HCMV IgG positive donors and in latently infected monocytic THP-1 cell
      lines. During the latency phase, only eight HCMV encoded microRNAs were detected
      in PBMCs, monocytes and in the THP-1 cells. Five originated from the UL region of
      the virus genome and three from the US region. Reactivation of the virus from
      latency, in monocytes obtained from the same donor, using dexamethasone restored
      the expression of all known HCMV encoded miRNAs including those that were absent
      during latency. We observed a shift in the abundance of the two arms of mir-US29
      between the productive and latency stages of the viral life cycle, suggesting
      that the star "passenger" form of this microRNA is preferentially expressed
      during latency. As a whole, our study demonstrates that HCMV expresses during the
      latency phase, both in vivo and in vitro, only a subset of its microRNAs, which
      may indicate that they play an important role in maintenance and reactivation of
      latency.

PMID- 26302753
TI  - Dual role of ERK5 in the regulation of T cell receptor expression at the T cell
      surface.
AB  - Regulation of the levels of the TCR/CD3 complex at the cell surface is critical
      to proper T cell development and mature T cell activation. We provide evidence
      that the MAPK ERK5 regulates the surface expression of the TCR/CD3 complex by
      controlling the degradation of the CD3zeta chain and the recovery of the complex
      after anti-CD3epsilon stimulation. ERK5 knockdown led to TCR/CD3 up-regulation at
      the cell surface and increased amounts of the CD3zeta chain. Inhibition of the
      MEK5-dependent phosphorylation status of the kinase domain of ERK5 in human T
      CD4(+) cells reduced CD3zeta ubiquitination and degradation, limiting TCR/CD3
      down-regulation in anti-CD3-stimulated cells. Moreover, TCR/CD3 recovery at the
      cell surface, after anti-CD3epsilon treatment, is impaired by ERK5 knockdown or
      pharmacological inhibition of autophosphorylation in the ERK5 C-terminal region.
      ERK5 loss in thymocytes augmented cellular CD3zeta and increased cell surface
      levels of TCR/CD3 on CD4(+)CD8(+) thymocytes. This correlated with enhanced
      generation of CD4(+)CD8(-)CD25(+) thymocytes. Our findings define ERK5 as a novel
      kinase that modulates the levels of TCR/CD3 at the cell surface by promoting
      CD3zeta degradation and TCR/CD3 recovery after TCR stimulation. 

PMID- 26302755
TI  - (Psychological) Distance Makes the Heart Grow Fonder: Effects of Psychological
      Distance and Relative Intelligence on Men's Attraction to Women.
AB  - Interpersonal attraction may be shaped by (a) one's psychological distance from a
      target (the subjective experience that a target is close to or far from the self)
      and (b) the perceived standing of a target on a trait relative to the self (as
      better or worse than the self). We propose that when evaluating a psychologically
      distant target, individuals may rely on abstract schemas (e.g., the desirability
      of a partner's traits) and prefer targets who possess more (vs. less) desirable
      qualities than themselves. However, when evaluating psychologically near targets,
      concrete contextual details of the environment (e.g., how a target's behavior
      affects self-evaluations in the moment) may determine individuals' attraction
      toward targets. Six studies revealed that when evaluating psychologically distant
      targets, men showed greater attraction toward women who displayed more (vs. less)
      intelligence than themselves. In contrast, when targets were psychologically
      near, men showed less attraction toward women who outsmarted them. 

PMID- 26302756
TI  - A Religious Worldview: Protecting One's Meaning System Through Religious
      Prejudice.
AB  - For some people, religion strongly influences their worldviews. We propose that
      religious outgroups threaten the foundational beliefs of people with strong
      religious worldviews (RWVs) by endorsing alternative belief systems and that this
      threat contributes to religious prejudice. To examine these ideas, we developed a
      measure of RWV strength and assessed the role of RWV threat in religious
      prejudice. Across five studies, strength of RWV was related to religious
      prejudice, including derogation and denial of alternative religious viewpoints,
      as well as support for suppressing, avoiding, and even aggressing against
      religious outgroups. These responses were strongest toward religious outgroups
      whose worldviews were the most different, and therefore most threatening.
      Mediational analyses revealed that strong RWV people expressed heightened
      prejudice because of the worldview threat posed by religious outgroup members.
      These findings indicate that the avoidance and subjugation of religious outgroups
      can serve as a worldview protection strategy for some people. 

PMID- 26302754
TI  - Methamphetamine induces trace amine-associated receptor 1 (TAAR1) expression in
      human T lymphocytes: role in immunomodulation.
AB  - The novel transmembrane G protein-coupled receptor, trace amine-associated
      receptor 1 (TAAR1), represents a potential, direct target for drugs of abuse and
      monoaminergic compounds, including amphetamines. For the first time, our studies
      have illustrated that there is an induction of TAAR1 mRNA expression in resting T
      lymphocytes in response to methamphetamine. Methamphetamine treatment for 6 h
      significantly increased TAAR1 mRNA expression (P < 0.001) and protein expression
      (P < 0.01) at 24 h. With the use of TAAR1 gene silencing, we demonstrate that
      methamphetamine-induced cAMP, a classic response to methamphetamine stimulation,
      is regulated via TAAR1. We also show by TAAR1 knockdown that the down-regulation
      of IL-2 in T cells by methamphetamine, which we reported earlier, is indeed
      regulated by TAAR1. Our results also show the presence of TAAR1 in human lymph
      nodes from HIV-1-infected patients, with or without a history of methamphetamine
      abuse. TAAR1 expression on lymphocytes was largely in the paracortical lymphoid
      area of the lymph nodes with enhanced expression in lymph nodes of HIV-1-infected
      methamphetamine abusers rather than infected-only subjects. In vitro analysis of
      HIV-1 infection of human PBMCs revealed increased TAAR1 expression in the
      presence of methamphetamine. In summary, the ability of methamphetamine to
      activate trace TAAR1 in vitro and to regulate important T cell functions, such as
      cAMP activation and IL-2 production; the expression of TAAR1 in T lymphocytes in
      peripheral lymphoid organs, such as lymph nodes; and our in vitro HIV-1 infection
      model in PBMCs suggests that TAAR1 may play an important role in methamphetamine 
      mediated immune-modulatory responses. 

PMID- 26302757
TI  - No evidence of transmission of chronic lymphocytic leukemia through blood
      transfusion.
AB  - Monoclonal B-cell lymphocytosis (MBL) is a precursor of chronic lymphocytic
      leukemia (CLL). Observations of MBL in blood donors raise concern that
      transmitted MBL may cause recipient CLL. Using a database with health information
      on 1.5 million donors and 2.1 million recipients, we compared CLL occurrence
      among 7413 recipients of blood from 796 donors diagnosed with CLL after donation
      cessation, and among 80, 431 recipients of blood from 7477 matched CLL-free
      donors. During follow-up, 12 and 107 cases of CLL occurred among the exposed and
      unexposed recipients, respectively, yielding a relative risk of 0.94 (95%
      confidence interval, 0.52-1.71). Analyses using the entire database showed no
      evidence of CLL clustering among recipients of blood from individual donors. In
      conclusion, when donor MBL was approximated by subsequent donor CLL diagnosis,
      data from 2 countries' entire computerized transfusion experience over more than
      30 years indicate that MBL/CLL transmission does not contribute importantly to
      recipient CLL risk.

PMID- 26302758
TI  - Prophylactic transfusion for pregnant women with sickle cell disease: a
      systematic review and meta-analysis.
AB  - Pregnancy in women with sickle cell disease is associated with adverse maternal
      and neonatal outcomes. Studies assessing the effects of prophylactic red blood
      cell transfusions on these outcomes have drawn inconsistent conclusions. The
      objective of this systematic review was to assess the effect of prophylactic
      compared with on-demand red blood cell transfusions on maternal and neonatal
      outcomes in women with sickle cell disease. A systematic search of several
      medical literature databases was conducted. Twelve studies involving 1291
      participants met inclusion criteria. The studies had moderate to high risk of
      bias. Meta-analysis demonstrated that prophylactic transfusion was associated
      with a reduction in maternal mortality (7 studies, 955 participants; odds ratio
      [OR], 0.23; 95% confidence interval [CI], 0.06-0.91), vaso-occlusive pain
      episodes (11 studies, 1219 participants; OR, 0.26; 95% CI, 0.09-0.76), pulmonary
      complications (9 studies, 1019 participants; OR, 0.25; 95% CI, 0.09-0.72),
      pulmonary embolism (3 studies, 237 participants; OR, 0.07; 95% CI, 0.01-0.41),
      pyelonephritis (6 studies, 455 participants; OR, 0.19; 95% CI, 0.07-0.51),
      perinatal mortality (8 studies, 1140 participants; OR, 0.43; 95% CI, 0.19-0.99),
      neonatal death (5 studies, 374 participants; OR, 0.26; 95% CI, 0.07-0.93), and
      preterm birth (9 studies, 1123 participants; OR, 0.59; 95% CI, 0.37-0.96). Event
      rates for most of the results were low. Prophylactic transfusions may positively
      impact several adverse maternal and neonatal outcomes in women with sickle cell
      disease; however, the evidence stems from a relatively small number of studies
      with methodologic limitations. A prospective, multicenter, randomized trial is
      needed to determine whether the potential benefits balance the risks of
      prophylactic transfusions. 

PMID- 26302760
TI  - Heart Disease Prevention in Young Women: Sounding an Alarm.

PMID- 26302759
TI  - Coronary Heart Disease Mortality Declines in the United States From 1979 Through
      2011: Evidence for Stagnation in Young Adults, Especially Women.
AB  - BACKGROUND: Coronary heart disease (CHD) mortality rates have fallen dramatically
      over the past 4 decades in the Western world. However, recent data from the
      United States and elsewhere suggest a plateauing of CHD incidence and mortality
      among young women. We therefore examined recent trends in CHD mortality rates in
      the United States according to age and sex. METHODS AND RESULTS: We analyzed
      mortality data between 1979 and 2011 for US adults >=25 years of age. We
      calculated age-specific CHD mortality rates and compared estimated annual
      percentage changes during 3 approximate decades of data (1979-1989, 1990-1999,
      and 2000-2011). We then used Joinpoint regression modeling to assess changes in
      trends over time on the basis of inflection points of the mortality rates. Adults
      >=65 years of age showed consistent mortality declines, which became even steeper
      after 2000 (women, -5.0%; men, -4.4%). In contrast, young men and women (<55
      years of age) initially showed a clear decline in CHD mortality from 1979 until
      1989 (estimated annual percentage change, -5.5% in men and -4.6% in women).
      However, the 2 subsequent decades saw stagnation with minimal improvement.
      Notably, young women demonstrated no improvements between 1990 and 1999
      (estimated annual percentage change, 0.1%) and only -1% estimated annual
      percentage change since 2000. Joinpoint analyses provided consistent results.
      CONCLUSIONS: The dramatic decline in CHD mortality since 1979 conceals major
      heterogeneities. CHD death rates in older groups are now falling steeply.
      However, young adults have experienced frustratingly small decreases in CHD
      mortality rates since 1990. The drivers of these major differences in CHD
      mortality trends by age and sex merit urgent study.

PMID- 26302761
TI  - Lymph node ratio as a prognostic factor in head and neck cancer patients.
AB  - BACKGROUND: Lymph node status is one prognostic factor in head and neck cancer.
      The purpose of this study is to investigate the prognostic value of lymph node
      ratio (LNR) in head and neck cancer patients who received surgery plus
      postoperative chemoradiotherapy. METHODS: From May 1991 to December 2012, a total
      of 117 head and neck cancer patients who received surgery plus postoperative
      chemoradiotherapy were analyzed. The primary sites were oral cavity (93),
      oropharynx (13), hypopharynx (6), and larynx (5). All patients had pathologically
      confirmed squamous cell carcinoma and 63 patients had neck lymph nodes
      metastasis. LNR was calculated for each patient. The endpoints were overall
      survival (OS), local failure-free survival (LFFS), and distant metastasis-free
      survival (DMFS). RESULTS: The median follow up time was 36 months, with a range
      from 3.4 to 222 months. The 3-year rates of OS, LFFS, and DMFS were 59.7, 70.3,
      and 81.8%, respectively. The median value of LNR for lymph nodes positive
      patients was 0.1. In univariate analysis, patients with an LNR value less than
      0.1 had better 3-year OS (67.0% vs.41.0%, p = 0.004), 3-year LFFS (76.1% vs.
      54.9%, p = 0.015) and 3-year DMFS (87.2% vs. 66.4%, p = 0.06). Multivariate
      analysis revealed that LNR was an independent prognostic factor for OS (hazard
      ratio [HR] = 2.92; 95% confidence interval [CI] = 1.367-6.242; p = 0.006) and
      LFFS (HR = 4.12; 95% CI = 1.604-10.59; p = 0.003). CONCLUSION: LNR is an
      important prognosis factor for OS and LFFS in head and neck cancer patients.

PMID- 26302762
TI  - Lifelong disturbance of serotonin transporter functioning results in fear
      learning deficits: Reversal by blockade of CRF1 receptors.
AB  - The inability to associate aversive events with relevant cues (i.e. fear
      learning) may lead to maladaptive anxiety. To further study the role of the
      serotonin transporter (SERT) in fear learning, classical fear conditioning was
      studied in SERT knockout rats (SERT(-/-)) using fear potentiation of the startle
      reflex. Next, fear acquisition and concomitant development of contextual
      conditioned fear were monitored during training. To differentiate between
      developmental and direct effects of reduced SERT functioning, effects of acute
      and chronic SSRI treatment were studied in adult rats. Considering the known
      interactions between serotonin and corticotropin-releasing factor (CRF), we
      studied the effect of the CRFR1 antagonist CP154,526 on behavioral changes
      observed and determined CRF1 receptor levels in SERT(-/-) rats. SERT(-/-) showed
      blunted fear potentiation and enhanced contextual fear, which resulted from a
      deficit in fear acquisition. Paroxetine treatment did not affect acquisition or
      expression of fear-potentiated startle, suggesting that disturbed fear learning
      in SERT(-/-) results from developmental changes and not from reduced SERT
      functioning. Although CRF1 receptor levels did not differ significantly between
      genotypes, CP154,526 treatment normalized both cue- and contextual fear in SERT(
      /-) during acquisition, but not expression of fear-potentiated startle. The
      disrupted fear acquisition and concomitant increase in contextual conditioned
      fear-potentiated startle fear in SERT(-/-) resembles the associative learning
      deficit seen in patients with panic disorder and suggests that normal SERT
      functioning is crucial for the development of an adequate fear neuro-circuitry.
      Moreover, the normalization of fear acquisition by CP154,526 suggests a role for
      central CRF signaling in the generalization of fear.

PMID- 26302763
TI  - Combination of intravenous S-ketamine and oral tranylcypromine in treatment
      resistant depression: A report of two cases.
AB  - Ketamine, a rapid-acting antidepressant and anti-suicidal agent, is thought to
      increase brain monoamine levels by enhancing monoamine release or inhibiting
      presynaptic monoamine-reuptake. Here we present two female inpatients suffering
      from treatment-resistant depression with recurrent severe suicidal crises
      receiving a combination of intravenous S-ketamine and oral tranylcypromine, which
      is a well-known irreversible monoamine oxidase (MAO) inhibitor. Since inhibition
      of monoamine-reuptake with concurrent blockade of MAO might trigger
      sympathomimetic crisis, this combination is considered hazardous. Nonetheless,
      cardiovascular parameters remained stable in both patients, while good anti
      suicidal effects were observed. Hence, we put serious doubt on whether monoamine
      reuptake inhibition is a relevant pharmacological effect of ketamine in humans.

PMID- 26302764
TI  - Complement Fixation Test: An Update of an Old Method for Diagnosis of Bullous
      Pemphigoid.
AB  - The complement fixation test (CFT) is a method traditionally used for diagnosis
      of gestational pemphigoid. Its performance in diagnosis of bullous pemphigoid
      (BP) has not been investigated in a large patient cohort. The aim of this single
      centre, retrospective, serological case-control study of 300 patients with BP and
      136 control patients was to analyse its operating characteristics. CFT was found
      to have a sensitivity of 71.7% and a specificity of 100%. Furthermore, CFT
      diagnosed 20 of 46 patients with BP (43.5%) who were negative for both BP180 and
      BP230 enzyme-linked immunoassays (ELISAs), 31 of 66 patients (47.0%) who were
      negative for indirect immunofluorescence of the oesophagus, 5 of 14 patients
      (35.7%) who were serologically negative for all investigated serological assays,
      and 7 of 18 patients (38.9%) in whom direct immunofluorescence was negative.
      Combination of CFT with all other serological assays resulted in a sensitivity of
      95.3%. In conclusion, CFT is suitable for the diagnosis of BP, and can help to
      diagnose serologically challenging cases. 

PMID- 26302765
TI  - Citrate Formulation Determines Filter Lifespan during Continuous Veno-Venous
      Hemofiltration: A Prospective Cohort Study.
AB  - INTRODUCTION: We conducted an 8-month prospective single-center observational
      study in patients with acute kidney injury treated with continuous veno-venous
      hemofiltration (CVVH) to compare the impact of two citrate formulations on filter
      lifespan (FLS). METHODS: Patients received CVVH at a delivered dose of 25
      ml/kg/h. Multivariable linear regression was performed to assess the influence of
      different variables on circuit lifespan. RESULTS: We included 59 patients, 28
      received the 10/2 formulation and 31 received the 18/0 formulation. Median
      (interquartile range) FLS was significantly prolonged with the 18/0 solution
      compared with the 10/2 solution (4.10 (2.45-5.75) vs. 2.68 (0.47-4.99) days, p =
      0.001). No confounding variables (difference in ionized calcium target, citrate
      flow or dose, platelet count, hematocrit, vascular access location) affecting
      filter capacity or lifespan between the 2 formulations were identified.
      CONCLUSIONS: Under similar conditions of CVVH and calcium targets, a
      Prismocitrate 18/0 formulation significantly improved FLS as compared with
      Prismocitrate 10/2.

PMID- 26302766
TI  - Pulmonary Function Test Abnormalities in Pediatric Inflammatory Bowel Disease.
AB  - BACKGROUND: Pulmonary involvement in adult patients with inflammatory bowel
      disease (IBD) seems more common than previously appreciated. Its prevalence and
      development over time in pediatric IBD patients are largely unknown. OBJECTIVES:
      The aim was to study lung function including fraction of exhaled nitric oxide
      (FeNO) and transfer capacity for carbon monoxide (TLCO) in pediatric IBD patients
      and to describe the longitudinal development in a subset of patients with lung
      function abnormalities. METHODS: Sixty-six measurements were made in 48 IBD
      patients (30 patients with Crohn's disease and 18 with ulcerative colitis) and
      108 matched controls. Patients with abnormal TLCO or elevated residual
      volume/total lung capacity (RV/TLC) ratios were invited for a follow-up.
      Statistical comparisons were made by nonparametric tests and ANOVA. RESULTS: TLCO
      was decreased in IBD patients [median: 88% predicted (interquartile range, IQR,
      22) vs. 99% predicted (IQR 19) in controls]. RV/TLC ratios were mildly elevated
      in patients with ulcerative colitis [32% (IQR 9) vs. 27% (IQR 8) in controls],
      and maximum expiratory flows at 50 and 25% of vital capacity were mildly reduced
      in patients with Crohn's disease. FeNO and disease activity did not correlate
      with lung function abnormalities. Abnormalities did not consistently persist over
      a median follow-up period of 34 months. CONCLUSIONS: This study supports evidence
      that variable and fluctuating pulmonary involvement also occurs in pediatric IBD
      patients. Its clinical significance is unclear.

PMID- 26302767
TI  - Combined Growth Hormone and Thyroid-Stimulating Hormone Deficiency in a Japanese
      Patient with a Novel Frameshift Mutation in IGSF1.
AB  - BACKGROUND: Recent reports have indicated that loss-of-function mutations in the
      immunoglobulin superfamily member 1 gene (IGSF1, OMIM 300888) cause congenital
      central hypothyroidism with macroorchidism. METHODS: We conducted a next
      generation sequencing-based comprehensive mutation screening for pituitary
      hormone deficiencies to elucidate molecular mechanisms other than anatomical
      abnormalities of the pituitary that might be responsible for multiple anterior
      hormone deficiency in a male patient who originally visited our institute
      complaining of short stature. He was born large for gestational age (4,370 g,
      +3.0 SD) after an obstructed labour. Endocrinological evaluation revealed growth
      hormone and thyroid-stimulating hormone deficiency. Magnetic resonance imaging
      showed a discontinuity of the pituitary stalk with an ectopic posterior lobe and
      a hypoplastic anterior lobe, likely explaining multiple anterior pituitary
      hormone deficiency. RESULT: We identified a novel hemizygous IGSF1 mutation
      (c.1137_1138delCA, p.Asn380Glnfs*6) in the patient. In reviewing the literature,
      we noticed that all reported Japanese male IGSF1 mutation carriers were born
      larger than mean standards for gestational age (mean birth weight SD score of
      +2.0, 95% confidence interval 1.0-3.0). CONCLUSION: This case suggests that more
      attention should be paid to intrauterine growth and birth history when patients
      are suspected of having an IGSF1 mutation.

PMID- 26302768
TI  - Recombinant Thrombomodulin Modulates Murine Colitis Possibly via High-Mobility
      Group Box 1 Protein Inhibition.
AB  - BACKGROUND AND AIM: Thrombomodulin (TM) is an anticoagulant cofactor protein. We
      hypothesized that its recombinant soluble TM (rhTM) form, widely used to treat
      disseminated intravascular coagulation, might have anti-inflammatory action in
      inflammatory bowel disease (IBD), possibly through its inhibition of high
      mobility group box 1 protein (HMGB1). METHODS: We investigated inflammatory
      effects of HMGB1 and anti-inflammatory effect of rhTM in dextran sulfate sodium
      (DSS)-treated mice, some cell lines and ulcerative colitis (UC) patients,
      particularly focusing on changes of vascular endothelial adhesion molecules.
      RESULTS: Treatments with rhTM significantly attenuated DSS-treated mice
      clinically and histologically. The mRNA levels of proinflammatory cytokines and
      adhesion molecules were decreased by rhTM. Increased inflammatory cells in the
      colonic mucosa strongly expressed HMGB1 in the cytoplasm in the DSS-treated mice
      and UC patients' colonic mucosa, which were significantly decreased by rhTM in
      mice. In in vitro experiments, rhTM significantly decreased the mRNA levels of
      tumor necrosis factor-alpha (TNF-alpha) and adhesion molecules increased by
      endotoxin exposures in RAW 264.7 (macrophage cell line) and bEND.3 cells
      (endothelial cell line), suggesting the proinflammatory role of HMGB1 in TNF
      alpha production from macrophages. CONCLUSIONS: These findings suggest that rhTM
      may be useful for the treatment of IBD by attenuating inflammatory cytokine
      production and adhesion molecule expression, partly because of its inhibition of
      HMGB1.

PMID- 26302769
TI  - Involvement of Chemokines and a CD4-Positive T Cell Subset in the Development of
      Conjunctival Secondary Lymphoid Follicles in an Atopic Keratoconjunctivitis Mouse
      Model.
AB  - BACKGROUND: Massive B cell lymphoid hyperplasia and its associated factors may
      play a role in exacerbating inflammation in allergic disorders. We here
      investigated the chemokines and CD4-positive T cell subset involved in the
      development of secondary lymphoid follicles (iCALT) in conjunctival tissues in an
      atopic keratoconjunctivitis mouse model (AKC mouse). METHODS: NC/Nga mice were
      divided into three groups: AKC (percutaneous sensitization and instillation of
      crude house dust mite antigen), AD (percutaneous sensitization only) and C
      (untreated control). Pathological changes in the conjunctival tissues of each
      group were investigated using histological and immunohistochemical detection of
      CD4 and CD20. Furthermore, tissue sections of iCALT (AKC-iCALT subgroup) and
      conjunctiva without iCALT (AKC-conjunctiva subgroup) were obtained from AKC mice
      using laser-assisted microdissection. mRNA expression of chemokine and T cell
      subset-related transcription factors were compared between the AKC-iCALT and AKC
      conjunctiva subgroups using polymerase chain reaction (PCR) array and real-time
      reverse transcription-PCR (RT-PCR) methods. RESULTS: iCALT with central
      aggregation of CD20-positive B cells and CD4-positive T cell infiltration
      surrounding B cells was observed in the palpebral conjunctival tissue of the AKC
      group, but not in that of the AD and C groups. Chemokine and T cell subset
      related transcription factor expression was confirmed using real-time RT-PCR,
      with significant increases in Ccl5, Ccl17, Cxl20, Cxcl3, Ccr7, Foxp3 and T-bet
      mRNA expression in the AKC-iCALT subgroup compared with those in the AKC
      conjunctiva subgroup. CONCLUSIONS: We concluded that CCL5, CCL17 and CCL20, as
      well as T-bet- and Foxp3-positive lymphocytes may be iCALT-related factors and
      that iCALT-related chemokines are worth evaluating as biomarkers.

PMID- 26302770
TI  - The psychosocial impact of inpatient management of monoamniotic  twin gestations.
AB  - OBJECTIVE: Monoamniotic twins require unique considerations in clinical
      management that challenge both clinicians and patients. The aim of this study was
      to assess the psychosocial impact of inpatient antepartum versus outpatient
      management for these patients. METHODS: Women with a history of a monoamniotic
      twin pregnancy between 2002 and 2012 were identified through a social media group
      and invited to participate in an original survey regarding their clinical
      management and psychological well-being during gestation. Results between
      patients managed with inpatient versus outpatient protocols were compared using
      the Fisher exact test. RESULTS: Participants (n = 197) were multinational.
      Planned inpatient management after 23 weeks gestation was reported in 76.2% of
      respondents. Participants in both groups endorsed persistent feelings of
      hopelessness or despair related to their pregnancies (42.4% of inpatients versus
      24.1% of outpatients, p = 0.089). Relationship strain between participants and
      their partners was similar in both the groups. Participants in the outpatient
      group were more likely to report feelings of guilt related to their infrequent
      monitoring (p = 0.01). Patient satisfaction with care was higher in the inpatient
      group. CONCLUSIONS: Inpatient management did not significantly increase measures
      of psychosocial stress as compared to outpatient management. Participants in the
      outpatient group reported feelings of guilt about their infrequent monitoring.
      Our findings provide increased understanding of the patient experience in these
      rare and challenging clinical circumstances.

PMID- 26302771
TI  - MicroRNA-137 is downregulated in human osteosarcoma and regulates cell
      proliferation and migration through targeting FXYD6.
AB  - BACKGROUND: In this work, we investigated the functional role of microRNA 137
      (miR-137) in regulating osteosarcoma both in vitro and in vivo. METHODS:
      Quantitative RT-PCR was used to examine the gene expressions of miR-137 in
      osteosarcoma cell lines and osteosarcoma tumors. 143B and Saos-2 cells were
      infected with lentivirus expressing miR-137 mimics (miR-137-mimic) to ectopically
      upregulate miR-137. In vitro cancer proliferation and migration were examined by
      MTT assay and transwell assay, respectively. Viral infected Saos-2 cells were
      also subcutaneously inoculated into null mice to evaluate the effect of miR-137
      upregulation on in vivo tumor growth. The interaction between miR-137 and its
      downstream target, FXYD6, was evaluated by dual-luciferase reporter assay and
      quantitative real-time PCR. FXYD6 was then subsequently upregulated in
      osteosarcoma cells to evaluate its effect on miR-137 regulation in osteosarcoma.
      RESULTS: We found that miR-137 was significantly downregulated in both
      osteosarcoma cell lines and osteosarcoma tumors. Lentiviral infection of miR-137
      mimic upregulated miR-137 gene expression, reduced in vitro proliferation and
      migration and inhibited in vivo osteosarcoma tumor growth. FXYD6 was verified to
      be directly interacting with miR-137, and its subsequent upregulation reversed
      the inhibitory effect of miR-137 upregulation in osteosarcoma. CONCLUSION: We
      revealed novel functional role of miR-137 in osteosarcoma regulation, likely
      through FXYD6 binding.

PMID- 26302772
TI  - Electronic and Morphological Studies of Conjugated Polymers Incorporating a Disk
      Shaped Polycyclic Aromatic Hydrocarbon Unit.
AB  - As more research findings have shown the correlation between ordering in organic
      semiconductor thin films and device performance, it is becoming more essential to
      exercise control of the ordering through structural tuning. Many recent studies
      have focused on the influence of side chain engineering on polymer packing
      orientation in thin films. However, the impact of the size and conformation of
      aromatic surfaces on thin film ordering has not been investigated in great
      detail. Here we introduce a disk-shaped polycyclic aromatic hydrocarbon building
      block with a large pi surface, namely, thienoazacoronenes (TACs), as a donor
      monomer for conjugated polymers. A series of medium bandgap conjugated polymers
      have been synthesized by copolymerizing TAC with electron donating monomers of
      varying size. The incorporation of the TAC unit in such semiconducting polymers
      allows a systematic investigation, both experimentally and theoretically, of the
      relationships between polymer conformation, electronic structure, thin film
      morphology, and charge transport properties. Field effect transistors based on
      these polymers have shown good hole mobilities and photoresponses, proving that
      TAC is a promising building block for high performance optoelectronic materials. 

PMID- 26302773
TI  - A tight-binding model for MoS2 monolayers.
AB  - We propose an accurate tight-binding parametrization for the band structure of
      MoS2 monolayers near the main energy gap. We introduce a generic and
      straightforward derivation for the band energies equations that could be employed
      for other monolayer dichalcogenides. A parametrization that includes spin-orbit
      coupling is also provided. The proposed set of model parameters reproduce both
      the correct orbital compositions and location of valence and conductance band in
      comparison with ab initio calculations. The model gives a suitable starting point
      for realistic large-scale atomistic electronic transport calculations. 

PMID- 26302774
TI  - Downregulation of IL6 Targeted MiR-376b May Contribute to a Positive IL6 Feedback
      Loop During Early Liver Regeneration in Mice.
AB  - BACKGROUND/AIMS: MicroRNAs (miRNAs) are a group of endogenous, small, noncoding
      RNAs implicated in a variety of biological processes, including cell
      proliferation, apoptosis, differentiation and metabolism. The present study aims
      to explore the potential role and molecular mechanism of miR-376b during the
      early phase of liver regeneration. METHODS: MiRNA profiling microarrays were used
      to assess the changes in miRNA expression. For functional analysis, cell
      proliferation, apoptosis assays, real time quantitative PCR and westernblot
      analysis were performed. RESULTS: The comprehensive miRNA expression profiling
      assays on regenerating liver tissues 4 h after partial hepatectomy (PH) showed
      that three miRNAs (miR-127, miR-376b and miR-494) located in the Dlk1-Gtl2 miRNA
      cluster were significantly downregulated. In vitro functional studies
      demonstrated that high-level interleukin 6 (IL6) inhibited the expression of miR
      376b, and miR-376b mimics treatment decreased cell proliferation and increased
      apoptosis. Further target analysis showed that miR-376b reduced the mRNA and
      protein expression levels of NF-kappa-B inhibitor zeta (NFKBIZ) and signal
      transducers and transcription activators 3 (STAT3). Additionally, IL6-induced miR
      376b downregulation would, in turn, increase the expression of IL-6 possibly via
      a feedback loop involving NFKBIZ or/and STAT3. CONCLUSION: During the early phase
      of liver regeneration, miR-376b expression was significantly decreased. Our
      findings reveal that a regulatory circuitry between miR-376b and IL-6 may exist,
      which trigger the initiation of liver regeneration.

PMID- 26302778
TI  - Erratum to: Long-acting methylphenidate formulations in the treatment of
      attention-deficit/hyperactivity disorder: a systematic review of head-to-head
      studies.

PMID- 26302777
TI  - Upregulation of microRNA-122 by farnesoid X receptor suppresses the growth of
      hepatocellular carcinoma cells.
AB  - BACKGROUND: microRNA-122 (miR-122) is the most abundant and specific miRNA in the
      liver. It acts as an important tumor suppressor in hepatocellular carcinoma (HCC)
      through regulating its target genes, but details of its own regulation are
      largely unknown. Farnesoid X receptor (FXR), a transcription factor with multiple
      functions, plays an important role in protecting against liver carcinogenesis,
      but it is unclear whether the anti-HCC effect of FXR is involved in the
      regulation of miR-122. METHODS: The levels of miR-122 and FXR in HCC tissues and
      cell lines were examined by quantitative real-time PCR (qRT-PCR). qRT-PCR was
      also used to detect the expression of miR-122 target genes at mRNA level, while
      Western blotting was used to analyze that of their protein products. The effect
      of FXR on the transcriptional activity of miR-122 promoter was evaluated by a
      luciferase reporter assay. Electrophoretic mobility shift assay (EMSA) and
      chromatin immunoprecipitation (ChIP) assay were performed to identify the FXR
      binding site within miR-122 promoter region. The cell proliferation was analyzed
      by a CCK-8 assay. The influence of FXR on tumor growth and miR-122 expression in
      vivo was monitored using HCC xenografts in nude mice. RESULTS: The expression of
      FXR was positively correlated with that of miR-122 in HCC tissues and cell lines.
      Activation of FXR in HCC cells upregulated miR-122 expression and in turn
      downregulated the expression of miR-122 target genes including insulin-like
      growth factor-1 receptor and cyclin G1. FXR bound directly to the DR2 element (
      338 to -325) in miR-122 promoter region, and enhanced the promoter's
      transcriptional activity. Functional experiments showed that the FXR-mediated
      upregulation of miR-122 suppressed the proliferation of HCC cells in vitro and
      the growth of HCC xenografts in vivo. CONCLUSIONS: miR-122 is a novel target gene
      of FXR, and the upregulation of miR-122 by FXR represses the growth of HCC cells,
      suggesting that FXR may serve as a key transcriptional regulator for manipulating
      miR-122 expression, and the FXR/miR-122 pathway may therefore be a novel target
      for the treatment of HCC.

PMID- 26302775
TI  - The adaptive evolution of virulence: a review of theoretical predictions and
      empirical tests.
AB  - Why is it that some parasites cause high levels of host damage (i.e. virulence)
      whereas others are relatively benign? There are now numerous reviews of virulence
      evolution in the literature but it is nevertheless still difficult to find a
      comprehensive treatment of the theory and data on the subject that is easily
      accessible to non-specialists. Here we attempt to do so by distilling the vast
      theoretical literature on the topic into a set of relatively few robust
      predictions. We then provide a comprehensive assessment of the available
      empirical literature that tests these predictions. Our results show that there
      have been some notable successes in integrating theory and data but also that
      theory and empiricism in this field do not 'speak' to each other very well. We
      offer a few suggestions for how the connection between the two might be improved.

PMID- 26302779
TI  - The gene patent controversy on Twitter: a case study of Twitter users' responses
      to the CHEO lawsuit against Long QT gene patents.
AB  - BACKGROUND: The recent Canadian lawsuit on patent infringement, filed by the
      Children's Hospital of Eastern Ontario (CHEO), has engendered a significant
      public debate on whether patenting genes should be legal in Canada. In part, this
      public debate has involved the use of social networking sites, such as Twitter.
      This case provides an opportunity to examine how Twitter was used in the context
      of this gene patent controversy. METHODS: We collected 310 English-language
      tweets that contained the keyword "gene patents" by using TOPSY.com and Twitter's
      built-in search engine. A content analysis of the messages was conducted to
      establish the users' perspectives on both CHEO's court challenge and the broader
      controversy over the patenting of human DNA. More specifically, we analyzed the
      users' demographics, geographic locations, and attitudes toward the CHEO position
      on gene patents and the patentability of human genes in principle. RESULTS: Our
      analysis has shown that messages tweeted by news media and health care
      organizations were re-tweeted most frequently in Twitter discussions regarding
      both the CHEO patent infringement lawsuit and gene patents in general. 34.8% of
      tweets were supportive of CHEO, with 52.8% of the supportive tweets suggesting
      that gene patents contravene patients' rights to health care access. 17.6% of the
      supportive tweets cited ethical and social concerns against gene patents. Nearly
      40% of tweets clearly expressed that human genes should not be patentable, and
      there were no tweets that presented perspectives favourable toward the patenting
      of human genes. CONCLUSION: Access to healthcare and the use of genetic testing
      were the most important concerns raised by Twitter users in the context of the
      CHEO case. Our analysis of tweets reveals an expectation that the CHEO lawsuit
      will provide an opportunity to clear the confusion on gene patents by
      establishing a legal precedent on the patentability of human genes in Canada. In
      general, there were no tweets arguing in favour of gene patents. Given the
      emerging role of social media in framing the public dialogue on these issues,
      this sentiment could potentially have an impact on the nature and tone of the
      Canadian policy debate.

PMID- 26302780
TI  - Prevalence of injury and associated factors among patients visiting the Emergency
      Departments of Amhara Regional State Referral Hospitals, Ethiopia: a cross
      sectional study.
AB  - BACKGROUND: Injury significantly affecting the health and well-being of the
      society. The prevalence tends to be higher in low income countries. The aim of
      this study was to assess the prevalence of injury and associated factors among
      patients visiting emergency departments of Amhara Regional State referral
      hospitals. METHODS: Institution based cross sectional study was conducted from
      March to April 2014. The systematic random sampling technique was employed to
      select the study participants. The data were collected using an interviewer
      administered questionnaire. Bivariate and multivariate logistic regressions were
      performed to identify factors associated with injury. Odds ratios with 95%
      confidence interval were computed to determine the level of significance. RESULT:
      The prevalence of injury was 55.6%. Being male (AOR = 2.8; 95% CI, 1.79-4.47),
      monthly income less than 34.2 USD (AOR = 1.89; 95% CI, 1.03-3.46), being age
      between 20 to 44 years (AOR = 2.25; 95% CI, 1.06-4.81), being a daily laborer
      (AOR = 6.27; 95% CI, 2.38-16.47), being a farmer (AOR = 2.9; 95% CI, 1.31-6.41)
      and being a substance user (AOR = 2. 16; 95 % CI, 1.18-3.96) were significantly
      associated with injury. CONCLUSION: The prevalence of injury was high. Being
      male, age 20 to 44 years, income < 34.2 USD, being a daily laborer, being a
      farmer and alcohol use were factors associated with injury. Hence, appropriate
      injury prevention strategy should be designed in order to lessen the magnitude of
      injury.

PMID- 26302781
TI  - Wave trains induced by circularly polarized electric fields in cardiac tissues.
AB  - Clinically, cardiac fibrillation caused by spiral and turbulent waves can be
      terminated by globally resetting electric activity in cardiac tissues with a
      single high-voltage electric shock, but it is usually associated with severe side
      effects. Presently, a promising alternative uses wave emission from
      heterogeneities induced by a sequence of low-voltage uniform electric field
      pulses. Nevertheless, this method can only emit waves locally near obstacles in
      turbulent waves and thereby requires multiple obstacles to globally synchronize
      myocardium and thus to terminate fibrillation. Here we propose a new approach
      using wave emission from heterogeneities induced by a low-voltage circularly
      polarized electric field (i.e., a rotating uniform electric field). We find that,
      this approach can generate circular wave trains near obstacles and they propagate
      outwardly. We study the characteristics of such circular wave trains and further
      find that, the higher-frequency circular wave trains can effectively suppress
      spiral turbulence. 

PMID- 26302782
TI  - Contextual modulation of value signals in reward and punishment learning.
AB  - Compared with reward seeking, punishment avoidance learning is less clearly
      understood at both the computational and neurobiological levels. Here we
      demonstrate, using computational modelling and fMRI in humans, that learning
      option values in a relative--context-dependent--scale offers a simple
      computational solution for avoidance learning. The context (or state) value sets
      the reference point to which an outcome should be compared before updating the
      option value. Consequently, in contexts with an overall negative expected value,
      successful punishment avoidance acquires a positive value, thus reinforcing the
      response. As revealed by post-learning assessment of options values, contextual
      influences are enhanced when subjects are informed about the result of the
      forgone alternative (counterfactual information). This is mirrored at the neural
      level by a shift in negative outcome encoding from the anterior insula to the
      ventral striatum, suggesting that value contextualization also limits the need to
      mobilize an opponent punishment learning system.

PMID- 26302783
TI  - Selective flow-induced vesicle rupture to sort by membrane mechanical properties.
AB  - Vesicle and cell rupture caused by large viscous stresses in ultrasonication is
      central to biomedical and bioprocessing applications. The flow-induced opening of
      lipid membranes can be exploited to deliver drugs into cells, or to recover
      products from cells, provided that it can be obtained in a controlled fashion.
      Here we demonstrate that differences in lipid membrane and vesicle properties can
      enable selective flow-induced vesicle break-up. We obtained vesicle populations
      with different membrane properties by using different lipids (SOPC, DOPC, or
      POPC) and lipid:cholesterol mixtures (SOPC:chol and DOPC:chol). We subjected
      vesicles to large deformations in the acoustic microstreaming flow generated by
      ultrasound-driven microbubbles. By simultaneously deforming vesicles with
      different properties in the same flow, we determined the conditions in which
      rupture is selective with respect to the membrane stretching elasticity. We also
      investigated the effect of vesicle radius and excess area on the threshold for
      rupture, and identified conditions for robust selectivity based solely on the
      mechanical properties of the membrane. Our work should enable new sorting
      mechanisms based on the difference in membrane composition and mechanical
      properties between different vesicles, capsules, or cells. 

PMID- 26302785
TI  - Proteinuria in Patients with Solid Tumors Treated with Ramucirumab: A Systematic
      Review and Meta-Analysis.
AB  - BACKGROUND: We performed a systematic review and meta-analysis of the risk of
      proteinuria associated with ramucirumab. METHODS: Eligible studies included
      randomized phase II and III trials of patients with solid tumors on ramucirumab,
      describing events of all-grade and high-grade proteinuria. RESULTS: Our search
      strategy yielded 170 potentially relevant citations from PubMed/Medline, CENTRAL
      Cochrane database, ASCO and ESMO meeting libraries. After exclusion of ineligible
      studies, a total of 11 clinical trials were considered eligible for the meta
      analysis. The relative risk (RR) of all-grade proteinuria was 3.31 (95% CI 2.48
      4.42; p < 0.00001). Moreover, the RR of high-grade proteinuria was 5.28 (95% CI
      2.32-12.01; p < 0.0001). CONCLUSIONS: Our meta-analysis has demonstrated that
      ramucirumab use is associated with an increased risk of all-grade and high-grade
      proteinuria. Early detection strategies should be employed in those patients to
      prevent the progression to more sinister renal disease.

PMID- 26302784
TI  - The use of clamped drainage to reduce blood loss in total hip arthroplasty.
AB  - BACKGROUND: Drainage is a routine practice used to reduce hematoma and blood loss
      following total hip arthroplasty. The aim of this study was to assess the effect
      of clamped drainage on blood loss and wound healing after total hip arthroplasty.
      METHODS: A prospective cohort of 44 patients with hip osteoarthritis or femur
      head necrosis undergoing total hip arthroplasty was randomized equally into two
      groups: 6-h postoperative clamped or non-clamped suction tube drainage. Body mass
      index, gender distribution, preoperative hemoglobin, hip pathology, and affected
      side were comparable between the two groups. Blood loss, hemoglobin levels, and
      wound healing complications were recorded and compared between groups. RESULTS:
      The drainage blood loss and calculated blood loss volumes were higher for the non
      clamped group. About 100 mL more blood loss was noticed in the non-clamped group.
      There was no significant difference in adverse events or need for transfusion.
      CONCLUSIONS: The present study showed a statistically significant reduction in
      postoperative drainage amount between clamped and unclamped drainage groups, but
      this difference was not large enough to warrant increased blood transfusion
      requirements in patients with unclamped drainage. Further studies are essential
      to define the critical period of clamping that is compatible with the dual
      objectives of reduced blood loss and lack of wound complications from hematoma.

PMID- 26302786
TI  - Bullous Delayed Pressure Urticaria Responding to Omalizumab.

PMID- 26302788
TI  - A structural hierarchy mediated by multiple nuclear factors establishes IgH locus
      conformation.
AB  - Conformation of antigen receptor gene loci spatially juxtaposes rearranging gene
      segments in the appropriate cell lineage and developmental stage. We describe a
      three-step pathway that establishes the structure of the 2.8-Mb immunoglobulin
      heavy chain gene (IgH) locus in pro-B cells. Each step uses a different
      transcription factor and leads to increasing levels of structural organization.
      CTCF mediates one level of compaction that folds the locus into several 250- to
      400-kb subdomains, and Pax5 further compacts the 2-Mb region that encodes
      variable (VH) gene segments. The 5' and 3' domains are brought together by the
      transcription factor YY1 to establish the configuration within which gene
      recombination initiates. Such stepwise mechanisms may apply more generally to
      establish regulatory fine structure within megabase-sized topologically
      associated domains. 

PMID- 26302787
TI  - Advancing epilepsy genetics in the genomic era.
AB  - Epilepsy is a group of disorders characterized by recurrent seizures, and is one
      of the most common neurological conditions. The genetic basis of epilepsy is
      clear from epidemiological studies and from rare gene discoveries in large
      families. The three major classes of epilepsy disorders are genetic generalized,
      focal and encephalopathic epilepsies, with several specific disorders within each
      class. Advances in genomic technologies that facilitate genome-wide discovery of
      both common and rare variants have led to a rapid increase in our understanding
      of epilepsy genetics. Copy number variant and genome-wide association studies
      have contributed to our understanding of the complex genetic architecture of
      generalized epilepsy, while genetic insights into the focal epilepsies and
      epileptic encephalopathies have come primarily from exome sequencing. It is
      increasingly clear that epilepsy is genetically heterogeneous, and novel gene
      discoveries have moved the field beyond the known contribution of ion channels to
      implicate chromatin remodeling, transcriptional regulation and regulation of the
      mammalian target of rapamycin (mTOR) protein in the etiology of epilepsy. Such
      discoveries pave the way for new therapeutics, some of which are already being
      studied. In this review, we discuss the rapid pace of gene discovery in epilepsy,
      as facilitated by genomic technologies, and highlight several novel genes and
      potential therapies.

PMID- 26302790
TI  - piRNA-guided slicing of transposon transcripts enforces their transcriptional
      silencing via specifying the nuclear piRNA repertoire.
AB  - PIWI clade Argonaute proteins silence transposon expression in animal gonads.
      Their target specificity is defined by bound ~23- to 30-nucleotide (nt) PIWI
      interacting RNAs (piRNAs) that are processed from single-stranded precursor
      transcripts via two distinct pathways. Primary piRNAs are defined by the
      endonuclease Zucchini, while biogenesis of secondary piRNAs depends on piRNA
      guided transcript cleavage and results in piRNA amplification. Here, we analyze
      the interdependencies between these piRNA biogenesis pathways in developing
      Drosophila ovaries. We show that secondary piRNA-guided target slicing is the
      predominant mechanism that specifies transcripts-including those from piRNA
      clusters-as primary piRNA precursors and defines the spectrum of Piwi-bound
      piRNAs in germline cells. Post-transcriptional silencing in the cytoplasm
      therefore enforces nuclear transcriptional target silencing, which ensures the
      tight suppression of transposons during oogenesis. As target slicing also defines
      the nuclear piRNA pool during mouse spermatogenesis, our findings uncover an
      unexpected conceptual similarity between the mouse and fly piRNA pathways.

PMID- 26302792
TI  - Targeting alpha7 Nicotinic Acetylcholine Receptor to Combat Inflammation in
      Cardio-Cerebral-Vascular Diseases.
AB  - BACKGROUND: Cardio-cerebral-vascular diseases, including myocardial infarction,
      atherosclerosis, hypertension, and stroke etc, are the major reasons for
      morbidity and mortality all over the world. Recent studies showed that
      inflammation exerts an important impact on the pathogenesis and development of
      cardio-cerebral-vascular diseases. "The cholinergic anti-inflammatory pathway",
      mainly modulated through alpha7 nicotinic acetylcholine receptor (alpha7nAChR),
      has attracted much attention. OBJECTIVE: The purpose of this review was to
      discuss the role of alpha7nAChR during the pathological processes in myocardial
      infarction, atherosclerosis, hypertension and stroke. RESULTS: Most of the
      existing literatures involved in studying on myocardial infarction,
      atherosclerosis, hypertension and stroke showed that activation of alpha7nAChR
      might be a potential strategy for the prevention and treatment of these diseases.
      CONCLUSION: Targeting alpha7nAChR to combat inflammation might be a novel therapy
      in cardiocerebral- vascular diseases.

PMID- 26302789
TI  - Noncatalytic PTEN missense mutation predisposes to organ-selective cancer
      development in vivo.
AB  - Inactivation of phosphatase and tensin homology deleted on chromosome 10 (PTEN)
      is linked to increased PI3K-AKT signaling, enhanced organismal growth, and cancer
      development. Here we generated and analyzed Pten knock-in mice harboring a C2
      domain missense mutation at phenylalanine 341 (Pten(FV)), found in human cancer.
      Despite having reduced levels of PTEN protein, homozygous Pten(FV/FV) embryos
      have intact AKT signaling, develop normally, and are carried to term.
      Heterozygous Pten(FV/+) mice develop carcinoma in the thymus, stomach, adrenal
      medulla, and mammary gland but not in other organs typically sensitive to Pten
      deficiency, including the thyroid, prostate, and uterus. Progression to carcinoma
      in sensitive organs ensues in the absence of overt AKT activation. Carcinoma in
      the uterus, a cancer-resistant organ, requires a second clonal event associated
      with the spontaneous activation of AKT and downstream signaling. In summary, this
      PTEN noncatalytic missense mutation exposes a core tumor suppressor function
      distinct from inhibition of canonical AKT signaling that predisposes to organ
      selective cancer development in vivo. 

PMID- 26302793
TI  - HIV-1 gp120: A Target for Therapeutics and Vaccine Design.
AB  - Although extraordinary progress has been made in the treatment and prevention of
      HIV infection, the AIDS pandemic continues to rage globally with 2.1 million
      infections and 1.6 million AIDS-related deaths reported in 2013. Until an
      effective vaccine is developed, new strategies for treatment and prevention are
      needed. Regarding the prevention of HIV infection, a major focus of prevention
      research in general and vaccine research in particular involves the interaction
      of the HIV-1 envelope protein gp120 with cell-surface receptors, with the hope
      that a greater understanding of these interactions will lead to the development
      of novel strategies aimed at preventing and even treating HIV-1 infection.
      Particular attention has been directed toward gaining a more precise
      understanding of the early events in transmission focusing on that critical
      window of time when HIV first establishes infection in the host. Here we describe
      some of the recent findings involving HIV-1 envelope interactions with cell
      surface receptors that are relevant to transmission and which may represent new
      opportunities to develop strategies to prevent HIV infection. 

PMID- 26302791
TI  - Adult Drosophila sensory neurons specify dendritic territories independently of
      dendritic contacts through the Wnt5-Drl signaling pathway.
AB  - Sensory neurons with common functions are often nonrandomly arranged and form
      dendritic territories in stereotypic spatial patterns throughout the nervous
      system, yet molecular mechanisms of how neurons specify dendritic territories
      remain largely unknown. In Drosophila larvae, dendrites of class IV sensory
      (C4da) neurons completely but nonredundantly cover the whole epidermis, and the
      boundaries of these tiled dendritic fields are specified through repulsive
      interactions between homotypic dendrites. Here we report that, unlike the larval
      C4da neurons, adult C4da neurons rely on both dendritic repulsive interactions
      and external positional cues to delimit the boundaries of their dendritic fields.
      We identify Wnt5 derived from sternites, the ventral-most part of the adult
      abdominal epidermis, as the critical determinant for the ventral boundaries.
      Further genetic data indicate that Wnt5 promotes dendrite termination on the
      periphery of sternites through the Ryk receptor family kinase Derailed (Drl) and
      the Rho GTPase guanine nucleotide exchange factor Trio in C4da neurons. Our
      findings thus uncover the dendritic contact-independent mechanism that is
      required for dendritic boundary specification and suggest that combinatory
      actions of the dendritic contact-dependent and -independent mechanisms may ensure
      appropriate dendritic territories of a given neuron. 

PMID- 26302794
TI  - Targeting the Eph-ephrin System with Protein-Protein Interaction (PPI)
      Inhibitors.
AB  - Eph-ephrin system is emerging as a new potential target in several diseases
      including cancer, diabetes, neurodegenerative diseases and inflammation. In the
      last decade, several efforts have been made to develop small molecule antagonists
      of Eph receptors. Both natural and synthetic compounds were discovered with
      (poly) phenol and steroidal derivatives on one side and the alpha1 agonist
      doxazosin, 2,5-dimethylpyrrol- 1-yl-benzoic acids and amino acid conjugates of
      lithocholic acid on the other. In the present paper we critically present
      available data for these compounds and discuss their potential usefulness as
      pharmacological tools or as candidates for a lead-optimization program. 

PMID- 26302795
TI  - CD6 as a Cell Surface Receptor and As a Target for Regulating Immune Responses.
AB  - CD6 has been exploited as a drug target as its expression is restricted,
      primarily to T cells, it has a well characterised cell surface ligand, CD166 and
      regulates T cell activation through a long cytoplasmic tail. CD6 can affect both
      the initiation and maintenance of T cell function in a negative and positive
      manner respectively so that it is important to understand these dual effects of a
      potential drug target. The effective mode of action of clinical monoclonal
      antibodies (mAbs) that recognise cell surface receptors including CD6 is commonly
      cytotoxic depletion of cells. It is not clear how current therapeutic strategies
      to target CD6 perturb function. With the benefit of new structural data, this
      review provides a critical analysis and interpretation of experiments in which
      various reagents have been tested and offers some suggestions as how more
      effective drugs may be developed. 

PMID- 26302796
TI  - Chimeric Antigen Receptor T Cells: Self-Replicating Drugs for Cancer.
AB  - The chimeric antigen receptor (CAR) technology started out as a tool to
      understand lymphocyte biology but rapidly developed into a T cell therapeutic
      agent for the treatment of cancers. Here, we describe the technological advances
      in the field of CARs and highlight critical components of its success.
      Additionally, we describe how various laboratories have worked toward developing
      new, safer, and more potent CARs for cancer.

PMID- 26302797
TI  - PLK1 Inhibition: Prospective Role for the Treatment of Pediatric Tumors.
AB  - Over the years, polo-like kinase 1 (PLK1) has garnered great interest as a
      therapeutic target. The PLK1 is a member of a highly conserved serine/threonine
      kinase family that plays pivotal roles in mitosis, cytokinesis and DNA damage
      response in eukaryotic cells. In this review, we summarize the functions of PLK1
      during cell cycle progression, its roles in human pediatric cancer and its value
      as a prognostic factor. Furthermore, we introduce the advances in pharmacological
      inhibition and the newly chemotherapeutic development of small-molecules to
      target PLK1 in cancer treatment. Finally, clinical trials with PLK1 inhibitors
      are briefly reviewed.

PMID- 26302798
TI  - Structure-Function Relationships of Class D Carbapenemases.
AB  - Class D carbapenemases, also known as Carbapenem-Hydrolyzing class D beta
      Lactamases (CHDLs) are of increasingly high clinical relevance, as they have been
      found in various important human pathogens, such as Acinetobacter baumannii and
      Klebsiella pneumoniae and contribute to the evolution of these pathogens towards
      extensively or totally-drug resistance (XDR/TDR) phenotypes. Essentially two main
      groups of phylogenetically-related enzymes have been described: one including the
      acquired OXA-23, OXA-24/40, OXA-51 and OXA-58 enzymes mostly in Acinetobacter
      baumannii, and the other including the OXA-48-related variants, i.e. OXA-54, OXA
      162, OXA-163 and OXA- 181. In this article, the biochemical and structural
      features of class D carbapenemases will be discussed. Furthermore, the
      mechanistic hypothesis based on recently obtained crystal structures of the
      native forms of class D carbapenemases and mutants thereof, in complex with
      relevant substrates or inhibitors, will be critically reviewed. Finally, the
      mechanism of inhibition by available inhibitors, some of which are currently in
      clinical development, will be discussed.

PMID- 26302799
TI  - Renin-Angiotensin-Aldosterone System: A Current Drug Target for the Management of
      Neuropathic Pain.
AB  - Renin-Angiotensin-Aldosterone System (RAAS) is well established in renovascular
      and cardiovascular functions. The modulators of this system are significantly
      used for regulating elevated blood pressure in human and animals. Recently, it
      has also been documented to produce neurological actions. The abnormalities of
      this system raise renin, angiotensin (AT), angiotensin converting enzyme (ACE)
      activity, and aldosterone in circulation and nerve tissues. In the nervous
      system, abundant rise of these components cause neuronal damage and
      neurodegeneration. ACE contributes to degradation of beta-amyloid in the brain,
      that is responsible for Alzheimer disease (AD). But, angiotensin converting
      enzyme-2 (ACE-2) mediated release of angiotensin1-7 (AT1-7) peptide in nerve
      tissue has potential neuroprotective actions. This review focuses on the current
      perspectives of the RAAS in neurodegeneration along with possible cellular and
      molecular mechanisms. Also, we have discussed the current evidence of RAAS
      modulators in the management of neuropathic pain in human and animals. Thus, we
      believe that, in the future, RAAS modulators may play a great role in the
      management of neuropathic pain and other neurodegenerative disorders such as AD,
      Parkinson disease (PD) and amyotrophic lateral sclerosis. But, more extensive
      clinical research is required for utilizing RAAS modulators in neurodegenerative
      disorders. 

PMID- 26302800
TI  - Human Immunodeficiency Virus-1 Cell-To-Cell Transmission And Antiviral
      Strategies: An Overview.
AB  - HIV-1 replicates by infecting new target cells either as cell-free viral particle
      or, much more efficiently, via cell-to-cell viral transmission. Cell-mediated
      viral spread, in which the infected cell directly transfers the viral particles
      to target cells via cell-cell contacts, in vitro is up to three orders of
      magnitude more efficient that transmission mediated by cell-free viral particles.
      Because of its potency, it has been suggested that current antiretroviral
      treatments could be less effective in blocking cell-to-cell viral transmission
      than cell-free. In this review I will present an overview of the drug-based
      antiretroviral approaches as well as how the recently identified class of anti
      HIV-1 broadly neutralizing antibodies could become part of an effective anti
      viral strategy. I will discuss how both treatment strategies can be guided by our
      consideration that cell-to-cell HIV-1 spread is a major route of viral spread
      also in vivo.

PMID- 26302801
TI  - Potential Role of (-)-Epigallocatechin-3-Gallate (EGCG) in the Secondary
      Prevention of Alzheimer Disease.
AB  - Medical advances in the last decades have increased the average life expectancy,
      but also the incidence and prevalence of age-associated neurodegenerative
      diseases. Alzheimer's disease (AD) is one of the most common neurodegenerative
      diseases and the most prevalent type of dementia. A plethora of different
      mechanisms contribute to AD, among which oxidative stress plays a key role in its
      development and progression. So far, there are no pharmacological treatments
      available and the current medications are mainly symptomatic. In the last years,
      dietary polyphenols have gained research attention due to their interesting
      biological activities, and more specifically their antioxidant properties. (-)-
      Epigallocatechin-3-gallate (EGCG) is a natural flavanol that has been extensively
      studied regarding its potential effects in AD. In this review we present the
      current in vitro and in vivo experimentation regarding the use of EGCG in AD. We
      also review the complex mechanisms of action of EGCG, not only limited to its
      antioxidant activity, which may explain its beneficial health effects.

PMID- 26302802
TI  - Is Senescence Reversible?
AB  - Senescence was originally identified by the finite lifespan of normal cells that
      is a consequence of telomere shortening with each cycle of DNA replication. Cells
      undergoing replicative senescence display pronounced morphological and
      biochemical changes such as flattening and/or enlargement, increases in p21(WAF1)
      and/or p16(INK4A), a senescence-associated secretory phenotype, and often
      senescence-associated heterochromatic foci. Senescence also occurs in tumor cells
      in response to various forms of chemotherapy or radiation (therapy-induced
      senescence), which could be the basis for prolonged or (ideally) permanent growth
      arrest. Alternatively, therapy-induced senescence could represent a means whereby
      tumor cells evade the potential toxicity of chemotherapy and radiation, allowing
      for the eventual re-emergence or escape from senescence that could lead to
      disease recurrence. This review discusses the experimental data in the literature
      that support the premise that senescence is potentially reversible through the
      inactivation of p53, p16(INK4A) and/or Rb, over-expression of Cdc2/cdk1 and
      survivin, the development of polyploidy, the survival of cancer stem cells and/or
      restoration of the nuclear landscape. If senescence is truly reversible, then the
      re-emergence of tumor cells from senescent arrest induced by chemotherapy or
      radiation could represent a barrier to the development of effective and curative
      cancer therapies.

PMID- 26302803
TI  - Molecular Mechanisms of Cholangiocarcinogenesis: New Potential Targets for
      Therapy.
AB  - Cholangiocarcinoma (CCA) is a heterogeneous group of dysplastic disorders
      affecting the biliary epithelium. It is the second most common primary liver
      tumor which accounts for around 3% of all gastrointestinal cancers. CCA is very
      deadly due to its aggressiveness, late diagnosis and high chemoresistance. The
      incidence is increasing worldwide and the therapeutic options are very limited.
      Radiotherapy, chemotherapy, surgery and/or liver transplantation may be indicated
      in patients who meet certain criteria, but chances of success are low. There is
      therefore increasing interest in understanding the molecular mechanisms involved
      in the pathogenesis of this cancer type and in identifying new targets for
      therapy. Current strategies are based on targeting key signaling pathways
      involved in proliferation, survival, apoptosis and migration. In this review, the
      most relevant molecular mechanisms involved in the pathogenesis of CCA are
      discussed and the main preclinical and clinical studies are highlighted.
      Moreover, future directions in basic and clinical research are indicated.

PMID- 26302804
TI  - The Key Role of Canonical Wnt/beta-catenin Signaling in Cartilage Chondrocytes.
AB  - Articular cartilage is a physiologically non-self-renewing avascular tissue with
      a unique cell type, the chondrocyte, which functions as producing and maintaining
      the extracellular matrix of cartilage. Cartilage differentiation and maintenance
      of homeostasis are finely tuned by a complex network of signaling molecules. The
      network sheds light on these mechanisms that appear to be highly relevant to both
      the identification of pathogenic key factors, and the development of biological
      approaches for cartilage regeneration. Wnt/beta-catenin signaling has been
      recognized as a key regulator of development and homeostasis in bone, cartilage,
      and joint. It plays important roles in many biological processes, including the
      condensation and differentiation of mesenchymal cells, the maintenance of mature
      articular cartilage phenotype, the hypertrophic maturation in the process of
      endochondral ossification, and tissue degeneration and regeneration. With regard
      to the importance of Wnt signaling pathways in regulating chondrocytes
      physiological and pathological activities, this article reviews the role of
      Wnt/beta-catenin signaling in chondrogenesis, chondrocytes development,
      degeneration, and the inhibitors of Wnt/beta-catenin signaling.

PMID- 26302805
TI  - Treatment of HCV-Related Mixed Cryoglobulinemia.
AB  - Mixed cryoglobulinemia syndrome (MCs) is a systemic vasculitis, involving skin,
      joints, peripheral nerves, and several internal organs. Hepatitis C virus (HCV)
      is recognized as the etiologic agent for the majority of MCs patients, as well as
      of number of autoimmune, lymphoproliferative, and neoplastic disorders. In this
      context, HCV-related MCs represents an important model autoimmune/ neoplastic
      disease triggered by a virus in humans. With regard the therapeutic strategies of
      MCs, we can treat these patients at different steps by means of etiological
      (antivirals), pathogenetic, symptomatic drugs (mainly immunosuppressors,
      corticosteroids, plasmapheresis). In the majority of individuals, MCs shows a
      mild, slow-progressive clinical course needing only symptomatic treatments,
      generally low doses of corticosteroids. Considering the etiopathogenesis of MCs,
      the eradication of HCV should be considered the gold standard in the treatment of
      MCs. The use of combined peg-interferon- alpha/ribavirin and/or novel antiviral
      drugs may lead to HCV eradication in a significant percentage of cases with
      possible remission of MCs. On the other hand, the presence of rapidly
      progressive, diffuse vasculitis with multiple organ involvement may be
      successfully treated with aggressive immunosuppressive and anti-inflammatory
      therapies, mainly based on cyclophosphamide or rituximab, high dose
      corticosteroids, and plasma aphaeresis. Moreover, sequential/combined antiviral
      or immunosuppressive treatments could represent an useful therapeutic strategy
      particularly in MCs patients with major clinical manifestations. The treatment of
      MCs should be decided for every patient according to the severity of clinical
      picture. Thus, a careful follow-up of the disease is necessary, with particular
      attention to the possibility of cancers onset, such as B-cell lymphoma. The
      present review focuses on the different therapeutic strategies in patients with
      MCs, including the treatment of cryoglobulinemic skin ulcers, which represents
      one of the most discouraging complications of the disease.

PMID- 26302806
TI  - Docking Studies for Multi-Target Drugs.
AB  - The most basic principle of drug action is found in the lock and key model, where
      the highest possible affinity for a target that also avoids side effects is
      desired. For many years this was understood as being "one drug, for one target,
      for one disease", however researchers began to observe that certain diseases are
      best treated with multi-target drugs. In recent years, studies have sought out
      polypharmacological compounds acting on multiple targets against complex
      (multifactorial) diseases, such as cancer, neurodegenerative disease, and certain
      infections. One of the computational tools used in research for multifunctional
      drugs is Molecular Docking. Through this methodology of Computer-Aided Drug
      Design, we observe complexes formed between ligands and interesting targets
      (often many), for a particular disease. This review reports on docking studies as
      used in investigations of new multi-target compounds; it also shows the various
      ways that such studies are used in the search for multifunctional compounds.

PMID- 26302808
TI  - Direct-Acting Antivirals for Hepatitis C Virus (HCV): The Progress Continues.
AB  - Treatment for hepatitis C virus (HCV) infection has progressed at remarkable
      speed. From poorly tolerated injectable therapy with very low cure rates,
      treatment has moved to highly effective well-tolerated all oral direct-acting
      antiviral therapies with cure rates above 90% for almost all patients
      populations. Direct-acting antivirals have developed out of an improved
      understanding of the viral lifecycle with recognition of targets that could be
      inhibited by small molecules. To date protease inhibitors, non-structural 5a
      inhibitors and nucleotide and non-nucleotide polymerase inhibitors have been
      developed. These agents have been used initially with peginterferon and ribavirin
      and subsequently in combination without the need for interferon. Rational
      combinations have overcome the major challenge of rapid emergence of drug
      resistance and second-generation agents in each class have improved safety and
      efficacy profiles with fewer drug-drug interactions and very few adverse effects.
      The progress of direct-acting antiviral development is outlined with a review of
      each class of agent as well as a discussion of challenges for the future.

PMID- 26302809
TI  - HIV-1 Matrix Protein p17 and its Receptors.
AB  - The HIV-1 matrix protein p17 (p17) plays a crucial role in the virus life cycle.
      It is released in the extracellular space from HIV-1-infected cells and
      accumulates in the tissues of patients, even in those successfully treated with
      highly active antiretroviral therapy. Extracellular p17 deregulates the
      biological functions of many different cells that are directly or indirectly
      implicated in AIDS pathogenesis. All p17 actions depend on interaction between
      its functional epitope (AT20), located at the protein N-terminal region, and
      different receptors expressed on target cells. This finding corroborates the
      importance of impeding p17/p17 receptors interaction as a contribution to block
      AIDS. In this article we review the interaction of p17 with heparan sulfate
      proteoglycans (HSPGs) and with the chemokine (C-X-C motif) receptor 1 (CXCR1) and
      2 (CXCR2). We provide details on how p17 interacts with its receptors and how
      these interactions are central to the p17 biological activities. Moreover, we
      highlight the existence of a p17 variant, named S75X, which displays opposite
      effects on B-cell proliferation as compared to p17. A two-site model for p17
      interaction with G-coupled receptors provides a possible explanation on how
      mutations naturally occurring within the primary amino acid structure can lead
      S75X to activate the Akt signaling pathway and to promote B-cell growth and
      transformation. Identification of p17 interaction with HSPGs, CXCR1 and CXCR2 as
      a fundamental event in supporting its activity could help to find new treatment
      approaches aimed at blocking all p17/p17 receptors interactions and,
      consequently, p17 detrimental activities. 

PMID- 26302810
TI  - HIV-1 TAT and IMMUNE DYSREGULATION in AIDS PATHOGENESIS: a THERAPEUTIC TARGET.
AB  - The HIV-1 transactivator Tat protein plays a key role in AIDS pathogenesis.
      Besides the Tat role as activator of HIV-1 transcription, it exerts several
      important functions on infected and uninfected cells. In fact, HIV-1 Tat is
      released by infected cells and is taken up by neighboring cells. In this way it
      regulates expression of viral and cellular genes and it modulates several
      cellular pathways leading to HIV-1 infection spreading and immune dysregulation.
      So far, Tat protein and the cellular pathways targeted by Tat may represent
      potential targets for new anti-HIV therapeutic approaches and vaccine development
      against AIDS. 

PMID- 26302807
TI  - Identifying Novel Targets for Treatment of Liver Fibrosis: What Can We Learn from
      Injured Tissues which Heal Without a Scar?
AB  - The liver is unique in that it is able to regenerate. This regeneration occurs
      without formation of a scar in the case of non-iterative hepatic injury. However,
      when the liver is exposed to chronic liver injury, the purely regenerative
      process fails and excessive extracellular matrix proteins are deposited in place
      of normal liver parenchyma. While much has been discovered in the past three
      decades, insights into fibrotic mechanisms have not yet lead to effective
      therapies; liver transplant remains the only cure for advanced liver disease. In
      an effort to broaden the collection of possible therapeutic targets, this review
      will compare and contrast the liver wound healing response to that found in two
      types of wound healing: scarless wound healing of fetal skin and oral mucosa and
      scar-forming wound healing found in adult skin. This review will examine wound
      healing in the liver and the skin in relation to the role of humoral and cellular
      factors, as well as the extracellular matrix, in this process. While several
      therapeutic targets are similar between fibrotic liver and adult skin wound
      healing, others are unique and represent novel areas for hepatic anti-fibrotic
      research. In particular, investigations into the role of hyaluronan in liver
      fibrosis and fibrosis resolution are warranted. 

PMID- 26302812
TI  - TET Family of Dioxygenases: Crucial Roles and Underlying Mechanisms.
AB  - DNA methylation plays an important role in the epigenetic regulation of mammalian
      gene expression. TET (ten-eleven translocation) proteins, newly discovered
      demethylases, have sparked great interest since their discovery. TET proteins
      catalyze 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine and 5
      carboxylcytosine in 3 consecutive Fe(II)- and 2-oxoglutarate (2-OG)-dependent
      oxidation reactions. TET proteins dynamically regulate global or locus-specific 5
      methylcytosine and/or 5-hydroxymethylcytosine levels by facilitating active DNA
      demethylation. In fact, in addition to their role as methylcytosine dioxygenases,
      TET proteins are closely related to histone modification, interact with metabolic
      enzymes as well as other proteins, and cooperate in transcriptional regulation.
      In this review, we summarize the recent progress in this exciting field,
      highlighting the molecular mechanism by which TET enzymes regulate gene
      expression and their functions in health and disease. We also discuss the
      therapeutic potential of targeting TET proteins and aberrant DNA modifications. 

PMID- 26302815
TI  - Systematically optimized coenzyme q10-loaded novel proniosomal formulation for
      treatment of photo-induced aging in mice: characterization, biocompatibility
      studies, biochemical estimations and anti-aging evaluation.
AB  - Environmental stress and advancing age is considered as the main cause of skin
      aging. However, environmental stress (especially UV radiations) accelerates the
      process of skin aging by manifolds. Coenzyme Q10 (CoQ10), an essential compound
      of cellular bioenergetics also acts as a strong antioxidant and protects the body
      against aging. High molecular weight and structure specific lipophilic nature of
      this molecule is a bottle neck in effective delivery through topical route.
      Preparation of a novel proniosomal (PN) gel formulation of CoQ10 employing
      systematic design of experiment (DoE) approach is a step ahead in transcending
      the constraints of the topical delivery. I-optimal mixture design was employed
      for systematic optimization of proniosomal formulation and evaluation of
      experimental data was performed for entrapment efficiency and in vitro release.
      Hydration of PN gel formulation with phosphate buffer (pH 7.5) results in
      submicron niosomes vesicles of spherical shape, which appeared dark against
      bright surroundings in TEM study. Animal skin was treated with UV radiations
      followed by treatment of PN gel CoQ10 and conventional CoQ10 present in a gel
      base. The effectiveness of the treatment was evaluated on the basis of
      biochemical estimation and histopathological studies. By using CoQ10 PN gel
      formulation, levels of superoxide dismutase (SOD), catalase (CA), glutathione
      (GSH) and total proteins were restored by 81.3%, 72.1%, 74.8 and 77.1%,
      respectively to that of control group. Histopathological studies revealed better
      protection of skin treated with CoQ10 PN gel compared to free CoQ10. Prepared PN
      gel was found undisturbing with the normal histology hence, tolerated by animal
      skin compare to conventional gel. 

PMID- 26302813
TI  - Coffee consumption and risk of endometrial cancer: a dose-response meta-analysis
      of prospective cohort studies.
AB  - This is a dose-response (DR) meta-analysis to evaluate the association of coffee
      consumption on endometrial cancer (EC) risk. A total 1,534,039 participants from
      13 published articles were added in this meta-analysis. The RR of total coffee
      consumption and EC were 0.80 (95% CI: 0.74-0.86). A stronger association between
      coffee intake and EC incidence was found in patients who were never treated with
      hormones, 0.60 (95% CI: 0.50-0.72), and subjects with a BMI >=25 kg/m(2), 0.57
      (95% CI: 0.46-0.71). The overall RRs for caffeinated and decaffeinated coffee
      were 0.66 (95% CI: 0.52-0.84) and 0.77 (95% CI: 0.63-0.94), respectively. A
      linear DR relationship was seen in coffee, caffeinated coffee, decaffeinated
      coffee and caffeine intake. The EC risk decreased by 5% for every 1 cup per day
      of coffee intake, 7% for every 1 cup per day of caffeinated coffee intake, 4% for
      every 1 cup per day of decaffeinated intake of coffee, and 4% for every 100 mg of
      caffeine intake per day. In conclusion, coffee and intake of caffeine might
      significantly reduce the incidence of EC, and these effects may be modified by
      BMI and history of hormone therapy. 

PMID- 26302816
TI  - Organocatalytic dynamic kinetic resolution of azlactones to construct chiral N
      acyl amino acid oxime esters.
AB  - A direct strategy to obtain N-acyl amino acid oxime esters has been developed
      through the dynamic kinetic resolution of azlactones with oximes. In the presence
      of a chiral bisguanidinium salt catalyst, a variety of chiral N-acyl amino acid
      oxime esters were generated in excellent enantiomeric excesses (up to 97%) and
      high yields (up to 99%). The active oxime esters could be used in dipeptide
      synthesis. 

PMID- 26302817
TI  - 30 mL Single- versus 80 mL double-balloon catheter for pre-induction cervical
      ripening: a randomized controlled trial.
AB  - OBJECTIVE: To compare the efficacy of an 80 mL double-balloon catheter versus a
      30 mL single-balloon catheter for pre-induction cervical ripening. METHODS: We
      performed a randomized controlled trial of women >=18 years with a singleton,
      vertex pregnancy, a reactive non-stress test, and a Bishop score <=5 comparing an
      80 mL double- versus a 30 mL single-balloon catheters for cervical ripening.
      Women were randomly assigned to the two catheter types, stratified 1:1 by
      nulliparity or multiparity. The primary outcome was achieving a Bishop score >=6
      at the time of catheter expulsion or removal assessed by chi-squared, stratified
      by parity. RESULTS: A total of 98 women were included in the analysis (50 in the
      80 mL double and 48 in the 30 mL single-balloon catheter groups). Among
      nulliparous women, a greater proportion of those randomized to the 80 mL double
      achieved a Bishop score >=6 at time of catheter removal (88.0% versus 28.0%; p <=
      0.001) and delivered vaginally (60.0% versus 32.0%; p = 0.047) compared to those
      with the 30 mL single-balloon catheter. We found no difference by catheter type
      in achieving a Bishop score >=6 or vaginal delivery among multiparous women.
      CONCLUSIONS: These findings suggest the 80 mL double-balloon catheter is more
      effective than the 30 mL single-balloon catheter for pre-induction cervical
      ripening and achieving a vaginal delivery in nulliparous women.

PMID- 26302818
TI  - First realization of the piezoelectronic stress-based transduction device.
AB  - We present the first realization of a monolithically integrated piezoelectronic
      transistor (PET), a new transduction-based computer switch which could
      potentially operate conventional computer logic at 1/50 the power requirements of
      current Si-based transistors (Chen 2014 Proc. IEEE ICICDT pp 1-4; Mamaluy et al
      2014 Proc. IWCE pp 1-2). In PET operation, an input gate voltage expands a
      piezoelectric element (PE), transducing the input into a pressure pulse which
      compresses a piezoresistive element (PR). The PR resistance goes down,
      transducing the signal back to voltage and turning the switch 'on'. This
      transduction physics, in principle, allows fast, low-voltage operation. In this
      work, we address the processing challenges of integrating chemically incompatible
      PR and PE materials together within a surrounding cage against which the PR can
      be compressed. This proof-of-concept demonstration of a fully integrated, stand
      alone PET device is a key step in the development path toward a fast, low-power
      very large scale integration technology. 

PMID- 26302811
TI  - Innate and Adaptive Immune Responses in Chronic HCV Infection.
AB  - Hepatitis C virus (HCV) remains a public health problem of global importance,
      even in the era of potent directly-acting antiviral drugs. In this chapter, I
      discuss immune responses to acute and chronic HCV infection. The outcome of HCV
      infection is influenced by viral strategies that limit or delay the initiation of
      innate antiviral responses. This delay may enable HCV to establish widespread
      infection long before the host mounts effective T and B cell responses. HCV's
      genetic agility, resulting from its high rate of replication and its error prone
      replication mechanism, enables it to evade immune recognition. Adaptive immune
      responses fail to keep up with changing viral epitopes. Neutralizing antibody
      epitopes may be hidden by decoy structures, glycans, and lipoproteins. T cell
      responses fail due to changing epitope sequences and due to exhaustion, a
      phenomenon that may have evolved to limit immune-mediated pathology. Despite
      these difficulties, innate and adaptive immune mechanisms do impact HCV
      replication. Immune-mediated clearance of infection is possible, occurring in 20
      50% of people who contract the disease. New developments raise hopes for
      effective immunological interventions to prevent or treat HCV infection.

PMID- 26302819
TI  - Sequence and Temperature Influence on Kinetics of DNA Strand Displacement at Gold
      Electrode Surfaces.
AB  - Understanding complex contributions of surface environment to tethered nucleic
      acid sensing experiments has proven challenging, yet it is important because it
      is essential for interpretation and calibration of indispensable methods, such as
      microarrays. We investigate the effects of DNA sequence and solution temperature
      gradients on the kinetics of strand displacement at heated gold wire electrodes,
      and at gold disc electrodes in a heated solution. Addition of a terminal double
      mismatch (toehold) provides a reduction in strand displacement energy barriers
      sufficient to probe the secondary mechanisms involved in the hybridization
      process. In four different DNA capture probe sequences (relevant for the
      identification of genetically modified maize MON810), all but one revealed a high
      activation energy up to 200 kJ/mol during hybridization, that we attribute to
      displacement of protective strands by capture probes. Protective strands contain
      4 to 5 mismatches to ease their displacement by the surface-confined probes at
      the gold electrodes. A low activation energy (30 kJ/mol) was observed for the
      sequence whose protective strand contained a toehold and one central mismatch,
      its kinetic curves displayed significantly different shapes, and we observed a
      reduced maximum signal intensity as compared to other sequences. These findings
      point to potential sequence-related contributions to oligonucleotide diffusion
      influencing kinetics. Additionally, for all sequences studied with heated wire
      electrodes, we observed a 23 K lower optimal hybridization temperature in
      comparison with disc electrodes in heated solution, and greatly reduced
      voltammetric signals after taking into account electrode surface area. We propose
      that thermodiffusion due to temperature gradients may influence both
      hybridization and strand displacement kinetics at heated microelectrodes, an
      explanation supported by computational fluid dynamics. DNA assays with surface
      confined capture probes and temperature gradients should not neglect potential
      influences of thermodiffusion as well as sequence-related effects. Furthermore,
      studies attempting to characterize surface-tethered environments should consider
      thermodiffusion if temperature gradients are involved. 

PMID- 26302820
TI  - Automatic and Online Pollen Monitoring.
AB  - BACKGROUND: Pollen are monitored in Europe by a network of about 400 pollen
      traps, all operated manually. To date, automated pollen monitoring has only been
      feasible in areas with limited variability in pollen species. There is a need for
      rapid reporting of airborne pollen as well as for alleviating the workload of
      manual operation. We report our experience with a fully automated, image
      recognition-based pollen monitoring system, BAA500. METHODS: The BAA500 sampled
      ambient air intermittently with a 3-stage virtual impactor at 60 m3/h in Munich,
      Germany. Pollen is deposited on a sticky surface that was regularly moved to a
      microscope equipped with a CCD camera. Images of the pollen were constructed and
      compared with a library of known samples. A Hirst-type pollen trap was operated
      simultaneously. RESULTS: Over 480,000 particles sampled with the BAA500 were both
      manually and automatically identified, of which about 46,000 were pollen. Of the
      automatically reported pollen, 93.3% were correctly recognized. However, compared
      with manual identification, 27.8% of the captured pollen were missing in the
      automatic report, with most reported as unknown pollen. Salix pollen grains were
      not identified satisfactorily. The daily pollen concentrations reported by a
      Hirst-type pollen trap and the BAA500 were highly correlated (r = 0.98).
      CONCLUSIONS: The BAA500 is a functional automated pollen counter. Its software
      can be upgraded, and so we expected its performance to improve upon training.
      Automated pollen counting has great potential for workload reduction and rapid
      online pollen reporting.

PMID- 26302821
TI  - A MicroRNA Signature in Gestational Diabetes Mellitus Associated with Risk of
      Macrosomia.
AB  - BACKGROUND/AIMS: MicroRNA (miRNA) is a small non-coding RNA molecule that
      functions in regulation of gene expression by targeting mRNA to affect its
      stability and/or translation. The aim of this study was to evaluate the miRNAs
      involvement in gestational diabetes mellitus (GDM), a well known risk factor for
      fetal overgrowth. METHODS: Differential microRNA expression in placental tissues
      of normal controls and women with GDM were identified by miRNA micorarray
      analysis and further confirmed by quantitative real-time PCR (qRT-PCR) on an
      independent set of normal and GDM placental tissues. Target genes of microRNAs
      were bioinformatically predicted and verified in vitro by Western blotting.
      RESULTS: Our results uncovered 9 miRNAs that were significantly deregulated in
      GDM samples: miR-508-3p was up-regulated and miR-27a, miR-9, miR-137, miR-92a,
      miR-33a, miR-30d, miR-362-5p and miR-502-5p were down-regulated. Bioinformatic
      approaches revealed that the microRNAs signature identifies gene targets involved
      in EGFR (epidermal growth factor receptor)-PI3K (phosphoinositide 3-Kinase)-Akt
      (also known as protein kinase B) pathway, a signal cascade which plays important
      roles in placental development and fetal growth. We found that the protein levels
      of EGFR, PI3K and phospho-Akt were up-regulated and PIKfyve (a FYVE finger
      containing phosphoinositide kinase), a negative regulator of EGFR signaling, was
      down-regulated significantly in GDM tissues. We also confirmed PIKfyve was a
      direct target of miR-508-3p. CONCLUSION: Our data identified a miRNA signature
      involvement in GDM which may contribute to macrosomia through enhancing EGFR
      signaling.

PMID- 26302823
TI  - Quantification and modification of the equilibrium dynamics and mechanics of a
      viral capsid lattice self-assembled as a protein nanocoating.
AB  - Self-assembling, protein-based bidimensional lattices are being developed as
      functionalizable, highly ordered biocoatings for multiple applications in
      nanotechnology and nanomedicine. Unfortunately, protein assemblies are soft
      materials that may be too sensitive to mechanical disruption, and their intrinsic
      conformational dynamism may also influence their applicability. Thus, it may be
      critically important to characterize, understand and manipulate the mechanical
      features and dynamic behavior of protein assemblies in order to improve their
      suitability as nanomaterials. In this study, the capsid protein of the human
      immunodeficiency virus was induced to self-assemble as a continuous, single
      layered, ordered nanocoating onto an inorganic substrate. Atomic force microscopy
      (AFM) was used to quantify the mechanical behavior and the equilibrium dynamics
      ("breathing") of this virus-based, self-assembled protein lattice in close to
      physiological conditions. The results uniquely provided: (i) evidence that AFM
      can be used to directly visualize in real time and quantify slow breathing
      motions leading to dynamic disorder in protein nanocoatings and viral capsid
      lattices; (ii) characterization of the dynamics and mechanics of a viral capsid
      lattice and protein-based nanocoating, including flexibility, mechanical strength
      and remarkable self-repair capacity after mechanical damage; (iii) proof of
      principle that chemical additives can modify the dynamics and mechanics of a
      viral capsid lattice or protein-based nanocoating, and improve their applied
      potential by increasing their mechanical strength and elasticity. We discuss the
      implications for the development of mechanically resistant and compliant
      biocoatings precisely organized at the nanoscale, and of novel antiviral agents
      acting on fundamental physical properties of viruses. 

PMID- 26302822
TI  - LDL in patients with subclinical hypothyroidism shows increased lipid
      peroxidation.
AB  - BACKGROUND: Population-based studies have demonstrated that subclinical
      hypothyroidism (SCH) is an independent risk factor for atherosclerosis (OR =
      1.9). However, this connection cannot be entirely explained by dyslipidemia
      accompanied by SCH. Lipid peroxidation also plays an important role in the
      development of atherosclerosis. In this study, we aimed to evaluate oxidative
      stress in SCH patients, as measured according to concentrations of hydroxy
      octadecadienoic acids (HODEs) and hydroxy-eicosatetraenoic acids (HETEs) in both
      plasma and low density lipoproteins (LDL). SUBJECTS AND METHODS: The
      concentrations of HODEs and HETEs in both LDL and plasma were examined in
      euthyroid (n = 10), mild SCH (4.5 <= TSH < 10 mU/L, n = 10), and significant SCH
      (TSH >= 10 mU/L, n = 10) subjects, using a liquid chromatograph-electrospray
      ionization- mass spectrometer. Then, we explored the relationship among LDL
      oxidation, TSH levels, and carotid intima-media thickness (IMT), a biomarker of
      subclinical atherosclerosis. RESULTS: Serum LDL-C levels and mean-IMT in the
      significant SCH group were higher than in the euthyroid group (p < 0.05). The
      HODE and HETE concentrations clearly increased in the significant SCH patients
      compared with the euthyroid subjects, but there was no difference between the
      mild SCH and euthyroid groups. Among all subjects, linear and significant
      positive correlations were identified between TSH and mean-IMT after adjustment
      for confounding factors (r = 0.480, p = 0.018). Both 9-HODE (r = 0.376, p =
      0.041) and 13-HODE (r = 0.447, p = 0.013) in LDL were linearly and positively
      correlated with TSH. The concentrations of HODEs (both 9-HODE and 13-HODE) in LDL
      were much higher in the thickened IMT group than in the normal IMT group (p = 
      .017 and 0.015, respectively). HODEs in LDL were also positively associated with
      mean-IMT. CONCLUSIONS: Our findings showed that lipid peroxidation was higher in
      the significant SCH patients than in the euthyroid subjects, which suggested that
      qualitative as well as quantitative changes in serum lipids resulting from SCH
      may add to atherosclerosis risk.

PMID- 26302824
TI  - Parental care protects traumatized Sri Lankan children from internalizing
      behavior problems.
AB  - BACKGROUND: Research in war-torn regions has mainly focused on the impact of
      traumatic experiences on individual mental health and has found high prevalence
      rates of psychiatric disorders in affected adults and children. However, little
      is known about the possible protective factors occurring in children's
      environments in the aftermath of mass trauma. Therefore, we conducted a cross
      sectional study with families in Northern Sri Lanka, a region that had been
      shattered by a long-lasting civil war and devastated by the Asian tsunami in
      2004. METHODS: Schoolchildren aged 7 to 11 (N = 359) were interviewed on the
      basis of standardized measures to assess children's exposure to traumatic events,
      mental health symptoms, and parenting behavior as perceived by children. All
      interviews were carried out by local senior counselors. RESULTS: Linear
      regression analyses identified exposure to mass trauma and family violence as
      significant risk factors of child mental health whereas parental care emerged as
      a significant factor associated with fewer behavior problems. In addition,
      parental care significantly moderated the relationship between mass trauma and
      internalizing behavior problems. CONCLUSIONS: Family characteristics seem to be
      strongly associated with children's mental health even in regions severely
      affected by mass trauma. This finding is particularly relevant for the
      development of targeted psychosocial interventions for children and families
      living in war torn areas.

PMID- 26302825
TI  - Hsa-miR-19a is associated with lymph metastasis and mediates the TNF-alpha
      induced epithelial-to-mesenchymal transition in colorectal cancer.
AB  - Lymph node metastasis is an important factor determining the outcome of
      colorectal cancer. Although epithelial-to-mesenchymal transition (EMT), TNF-alpha
      and microRNA (miRNA) have been found to play important roles in lymph node
      metastasis, the underlying molecular mechanism remains unclear. Here we reported
      that high expression of microRNA-19a (miR-19a) was associated with lymph node
      metastasis and played an important role in TNF-alpha-induced EMT in colorectal
      cancer (CRC) cells. We analyzed miR-19a expression in surgical tissue specimens
      from 11 CRC patients and 275 formalin-fixed, paraffin-embedded CRC patients. We
      found that miR-19a was up-regulated in CRC tissues and high expression of miR-19a
      was significantly associated with lymph node metastasis. We further analyzed miR
      19a lymph node metastasis signature in an external validation cohort of 311 CRC
      cases of the TCGA. MiR-19a was found to be significantly associated with lymph
      node metastasis in rectal cancer. In vitro, we showed that overexpression of miR
      19a in human CRC cell lines promoted cell invasion and EMT. Furthermore, miR-19a
      was up-regulated by TNF-alpha and miR-19a was required for TNF-alpha-induced EMT
      and metastasis in CRC cells. Collectively, miR-19a played an important role in
      mediating EMT and metastatic behavior in CRC. It may serve as a potential marker
      of lymph node metastasis. 

PMID- 26302827
TI  - Commentary to "27 years of experience with the comprehensive surgical management
      of prune belly syndrome".

PMID- 26302826
TI  - Community-level effect of the reproductive health vouchers program on out-of
      pocket spending on family planning and safe motherhood services in Kenya.
AB  - BACKGROUND: Although vouchers can protect individuals in low-income countries
      from financial catastrophe and impoverishment arising from out-of-pocket
      expenditures on healthcare, their effectiveness in achieving this goal depends on
      whether both service and transport costs are subsidized as well as other factors
      such as service availability in a given locality and community perceptions about
      the quality of care. This paper examines the community-level effect of the
      reproductive health vouchers program on out-of-pocket expenditure on family
      planning, antenatal, delivery and postnatal care services in Kenya. METHODS: Data
      are from two rounds of cross-sectional household surveys in voucher and non
      voucher sites. The first survey was conducted between May 2010 and July 2011
      among 2,933 women aged 15-49 years while the second survey took place between
      July and October 2012 among 3,094 women of similar age groups. The effect of the
      program on out-of-pocket expenditure is determined by difference-in-differences
      estimation. Analysis entails comparison of changes in proportions, means and
      medians as well as estimation of multivariate linear regression models with
      interaction terms between indicators for study site (voucher or non-voucher) and
      period of study (2010-2011 or 2012). RESULTS: There were significantly greater
      declines in the proportions of women from voucher sites that paid for antenatal,
      delivery and postnatal care services at health facilities compared to those from
      non-voucher sites. The changes were also consistent with increased uptake of the
      safe motherhood voucher in intervention sites over time. There was, however, no
      significant difference in changes in the proportions of women from voucher and
      non-voucher sites that paid for family planning services. The results further
      show that there were significant differences in changes in the amount paid for
      family planning and antenatal care services by women from voucher compared to
      those from non-voucher sites. Although there were greater declines in the average
      amount paid for delivery and postnatal care services by women from voucher
      compared to those from non-voucher sites, the difference-in-differences estimates
      were not statistically significant. CONCLUSIONS: The reproductive health vouchers
      program in Kenya significantly contributed to reductions in the proportions of
      women in the community that paid out-of-pocket for safe motherhood services at
      health facilities.

PMID- 26302828
TI  - Prospective evaluation of the long-term effects of clinical voiding reeducation
      or voiding school for lower urinary tract conditions in children.
AB  - INTRODUCTION: Although the short-term effects of urotherapy as a treatment
      strategy for lower urinary tract (LUT) conditions have been well documented, the
      long-term effects remain largely unknown. A better insight into the long-term
      effects of urotherapy could improve the clinical guidelines for children with
      incontinence. OBJECTIVE: This study aimed to investigate the long-term effects
      (i.e., from 6 months to 2 years) from a clinical voiding reeducation program
      among children with LUT conditions. STUDY DESIGN: This study was a prospective
      continuation of the follow-up study of Hoebeke et al. (2011). Thirty-eight
      children (mean age 9 years) with LUT conditions completed an extensive clinical
      voiding reeducation program (VS). Data on medication, voiding, drinking, pelvic
      floor tone, uroflowmetry, and incontinence were recorded 2 years after the VS.
      These data were compared with the outcomes at 6 months follow-up and at intake
      before voiding school. RESULTS: Six months after voiding school, 22 children
      continued having daytime incontinence (ID) and/or enuresis (EN). Six of them
      became dry at 2 years. Conversely, 16 children were dry at 6 months, of which
      eight relapsed at 2 years. Whereas all parameters significantly improved 6 months
      after VS, further improvements from 6 months to 2 years could only be noticed for
      the proportion of children suffering from overactive bladder (92% at intake, 55%
      at 6-month follow-up and 18% at 2-year follow-up) (Figure). Fluid intake and
      pelvic floor tone improved after 6 months, but showed a significant relapse after
      2 years (P = 0.013, P = 0.031, respectively). DISCUSSION: Hoebeke et al. (2011)
      concluded that results continued to improve after VS. No further improvements
      could be noticed 2 years after VS, although individual shifts were present. The
      results of the present study underline the value of long-term follow-up to detect
      those needing ongoing treatment to prevent relapse. Fluid intake and pelvic floor
      tone deteriorated from 6 months to 2 years. It could be hypothesized that
      inadequate fluid intake, possibly leading to decreased voided volumes, may be
      seen as an indicator for upcoming incontinence relapse. It could be stated that
      adequate fluid intake and pelvic floor tone may play a role in remaining
      continent for the long term. Study limitations should be considered. The study
      population was heterogeneous and rather small. Together with other missing
      values, this could have influenced the results. CONCLUSION: Close individual,
      long-term follow-up after clinical voiding reeducation in children is recommended
      in order to timely detect and prevent potential relapse.

PMID- 26302829
TI  - Use of holmium laser for urethral strictures in pediatrics: A prospective study.
AB  - INTRODUCTION: The management of urethral strictures is very challenging and
      requires the wide expertise of different treatment modalities ranging from
      endoscopic procedures to open surgical interventions. OBJECTIVE: To assess the
      effectiveness and complications of retrograde endoscopic holmium: yttrium
      aluminum-garnet laser (Ho: YAG) urethrotomy (HLU) for the treatment of pediatric
      urethral strictures. PATIENTS AND METHODS: From January 2010 to January 2013, 29
      male pediatric patients with a mean age of 5.9 years and primary urethral
      strictures 0.5-2 cm long were treated using HLU. The stricture length was <1 cm
      in 16 (55%) patients and >1 cm in 13 (45%). Fifteen (51.7%) patients had an
      anterior urethral stricture, while 14 (48.3%) had a posterior urethral stricture.
      No positive history was found in 14 (48.3%) patients for the stricture disease,
      while six (20.7%) had straddle trauma and nine (31%) had an iatrogenic stricture.
      All of the patients were pre-operatively investigated and at 3 and 6 months
      postoperation by uroflowmetry and voiding cystourethrography (VCUG). If there
      were suspicious voiding symptoms, selective uroflowmetry and VCUG were performed
      at 12 months postoperation. RESULTS: The mean operation time was 31.7 min (20-45
      min). Twenty-three (79.3%) and 18 (62.1%) patients showed normal urethra on VCUG
      with improvement of symptoms at 3 and 6 months, respectively. Thus, recurrence
      was 37.9% after 6 months of follow-up. The mean pre-operative peak urinary flow
      rate (Qmax) was 6.47 ml/s. The mean postoperative Qmax at 3 and 6 months was
      17.17 ml/s and 15.35 ml/s, respectively. The success rate and flowmetry results
      did not show any statistical significance in relation to site, length and cause
      of the strictures. The other 11 patients who failed to improve underwent repeated
      HLU sessions: 4/11 (36.3%) achieved successful outcomes. Among the seven patients
      with failed HLU for the second time, a third session was conducted. However, only
      one patient (14.2%) was cured, while open repair was needed for the remaining
      six. DISCUSSION: One study has previously been published on the management of
      pediatric urethral strictures using HLU. The present results are similar to short
      term studies after a single session of visual internal urethrotomy using cold
      knife (VIU). In the present study, the length, location and cause of strictures
      did not significantly affect the results. However, the outcomes with strictures
      <1 cm were better than strictures >1 cm, although patients with strictures >2 cm
      were excluded. In the present study, the success rates among patients with second
      and third sessions of HLU were 36.3% and 14.2%, respectively. This was similar to
      other studies, which reported low success rate with the second session of VIU.
      The present study was limited by the relatively short period of follow-up and the
      small number of patients. However, it was the first prospective study evaluating
      HLU for pediatric strictures. The use of flowmetry and VCUG for evaluation of all
      patients added to the strength of the study. CONCLUSION: HLU can be safely used
      with good success rates for the treatment of primary urethral strictures (<2 cm)
      in children. Repeat HLU (more than twice) adds little to success.

PMID- 26302830
TI  - Slow transit constipation and lower urinary tract dysfunction.
AB  - INTRODUCTION: Many theories have been proposed for the coexistence of
      constipation and lower urinary tract dysfunction (LUTD), such as bladder
      compression from a distended rectum and stimulation of sacral reflexes from a
      full rectum. In these cases, successful treatment of constipation should result
      in resolution of bladder symptoms. Some children have refractory constipation and
      others respond well to treatment, but once treatment is discontinued most
      children relapse back into their constipation. This may indicate the existence of
      a defect in colon motility, with a persistent peristalsis problem. The existence
      of a common neuromuscular disorder should be the base for both bladder and bowel
      dysfunction (BBD). OBJECTIVE: To study colonic transit time (CTT) in children and
      adolescents with refractory constipation and lower urinary tract symptoms (LUTS).
      MATERIALS AND METHODS: A total of 15 children (mean age 9.7 years) with
      refractory constipation and LUTS were evaluated with: standardized medical
      history; physical examination; bladder and bowel diaries; Bristol stool scale;
      Rome III criteria; Dysfunctional Voiding Scoring System (DVSS); ultrasound
      examination of the kidneys and urinary tract, and measurement of rectal diameter;
      urodynamic evaluation; and a CTT study using radiopaque markers. RESULTS:
      Urodynamic features were abnormal in 13 out of 15 children: 10 (66.7%) presented
      with detrusor overactivity (DO) and voiding dysfunction (VD), two (16.7%) had
      isolated DO, and one (8.3%) had a VD. The CTT study was abnormal in 12 out of 15
      children: nine (60%) presented with slow transit constipation, three (20%) had
      outlet obstruction, and three (20%) had a normal CTT study. When comparing CTT
      and LUTD, nine (100%) children with slow transit constipation (STC) and three
      (50%) with no STC had DO (P = 0.04). Seven (77.8%) children with STC and three
      (50%) with no STC had VD (P = 0.29). The DVSS scores ranged from 6 to 21. The
      subgroup with STC had a DVSS score that was significantly higher than that of the
      subgroup with noF STC (Figure). DISCUSSION: The present study showed a high
      prevalence of STC in children and adolescents with refractory constipation and
      LUTS. This was in accordance with previous studies that have demonstrated a rate
      of 50-60% of STC in children with refractory constipation. In addition, DO was
      found to be associated with STC, which raises the chance for the existence of a
      common neuromuscular disorder to be the base for both bladder and bowel
      dysmotility. The limitation of this study was the number of participants.
      CONCLUSIONS: The present study demonstrated an association between DO and STC.

PMID- 26302831
TI  - Surface modulation of silicon nitride ceramics for orthopaedic applications.
AB  - Silicon nitride (Si3N4) has a distinctive combination of material properties such
      as high strength and fracture toughness, inherent phase stability, scratch
      resistance, low wear, biocompatibility, hydrophilic behavior, excellent
      radiographic imaging and resistance to bacterial adhesion, all of which make it
      an attractive choice for orthopaedic implants. Unlike oxide ceramics, the surface
      chemistry and topography of Si3N4 can be engineered to address potential in vivo
      needs. Morphologically, it can be manufactured to have an ultra-smooth or highly
      fibrous surface structure. Its chemistry can be varied from that of a silica-like
      surface to one which is predominately comprised of silicon-amines. In the present
      study, a Si3N4 bioceramic was subjected to thermal, chemical, and mechanical
      treatments in order to induce changes in surface composition and features. The
      treatments included grinding and polishing, etching in aqueous hydrofluoric acid,
      and heating in nitrogen or air. The treated surfaces were characterized using a
      variety of microscopy techniques to assess morphology. Surface chemistry and
      phase composition were determined using X-ray photoelectron and Raman
      spectroscopy, respectively. Streaming potential measurements evaluated surface
      charging, and sessile water drop techniques assessed wetting behavior. These
      treatments yielded significant differences in surface properties with isoelectric
      points ranging from 2 to 5.6, and moderate to extremely hydrophilic water contact
      angles from ~65 degrees  to ~8 degrees . This work provides a basis for future in
      vitro and in vivo studies which will examine the effects of these treatments on
      important orthopaedic properties such as friction, wear, protein adsorption,
      bacteriostasis and osseointegration. STATEMENT OF SIGNIFICANCE: Silicon nitride
      (Si3N4) exhibits a unique combination of bulk mechanical and surface chemical
      properties that make it an ideal biomaterial for orthopaedic implants. It is
      already being used for interbody spinal fusion cages and is being developed for
      total joint arthroplasty. Its surface texture and chemistry are both highly
      tunable, yielding physicochemical combinations that may lead to enhanced
      osseointegration and bacterial resistance without compromising bulk mechanical
      properties. This study demonstrates the ease with which significant changes to
      Si3N4's surface phase composition, charging, and wetting behavior can be induced,
      and represents an initial step towards a mechanistic understanding of the
      interaction between implant surfaces and the biologic environment.

PMID- 26302832
TI  - Bat aggregation mediates the functional structure of ant assemblages.
AB  - In the Guianese rainforest, we examined the impact of the presence of guano in
      and around a bat roosting site (a cave). We used ant communities as an indicator
      to evaluate this impact because they occupy a central place in the functioning of
      tropical rainforest ecosystems and they play different roles in the food web as
      they can be herbivores, generalists, scavengers or predators. The ant species
      richness around the cave did not differ from a control sample situated 500m away.
      Yet, the comparison of functional groups resulted in significantly greater
      numbers of detritivorous fungus-growing and predatory ant colonies around the
      cave compared to the control, the contrary being true for nectar and honeydew
      feeders. The role of bats, through their guano, was shown using stable isotope
      analyses as we noted significantly greater delta(15)N values for the ant species
      captured in and around the cave compared to controls. 

PMID- 26302833
TI  - Tank bromeliads as natural microcosms: a facultative association with ants
      influences the aquatic invertebrate community structure.
AB  - Many tank bromeliads have facultative relationships with ants as is the case in
      French Guiana between Aechmea aquilega (Salib.) Griseb. and the trap-jaw ant,
      Odontomachus haematodus Linnaeus. Using a redundancy analysis, we determined that
      the presence of O. haematodus colonies is accompanied by a greater quantity of
      fine particulate organic matter in the water likely due to their wastes. This
      increase in nutrient availability is significantly correlated with an increase in
      the abundance of some detritivorous taxa, suggesting a positive bottom-up
      influence on the aquatic macroinvertebrate communities living in the A. aquilega
      wells. On the other hand, the abundance of top predators is negatively affected
      by a lower number of available wells due to ant constructions for nesting,
      releasing a top-down pressure that could also favor lower trophic levels. 

PMID- 26302834
TI  - Genetic diversity of the bacterial wilt pathogen Ralstonia solanacearum using a
      RAPD marker.
AB  - Bacterial wilt caused by Ralstonia solanacearum is a destructive disease of many
      economically important crop species. A significant variation in wilt incidence
      and severity in eggplant and potato was observed among the growing areas
      surveyed. R. solanacearum isolates obtained both from eggplant and potato belong
      to biovar III, while isolates from eggplant belong to race 1 and isolates
      obtained from potato belong to race 3. Random amplified polymorphic DNA (RAPD)
      technique was used as a tool for assessing genetic variation and relationship
      among seven isolate groups of R. solanacearum viz., RsB-1, RsB-2, RsB-3, RsP-1,
      RsP-2, RsP-3 and RsP-4, consisting in a total of 28 isolates. Out of the RAPD
      markers used, amplification with four decamer primers produced 70 bands with
      sizes ranging from 100 to 1400 bp. Out of 70 bands, 68 bands (97.06%) were
      polymorphic and two bands (2.94%) were monomorphic amongst the seven R.
      solanacearum isolates group. The Unweighted Pair Group Method of Arithmetic Means
      (UPGMA) dendrogram constructed from Nei's genetic distance produced two main
      clusters of the seven isolates of R. solanacearum. The isolates RsB-1, RsB-2, RsB
      3 and R-4 grouped in cluster I, while RsP-2, RsP-3 and RsP-4 grouped in cluster
      II. The highest intra-variety similarity index (Si) was found in RsB-1 isolate
      (86.35%) and the lowest one in RsP-2 (56.59%). The results indicated that
      relatively higher and lower levels of genetic variation were found in RsP-3 and
      RsB-3, respectively. The coefficient of gene differentiation (G(st)) was 0.5487,
      reflecting the existence of a high level of genetic variations among seven
      isolates of R. solanacearum. Comparatively higher genetic distance (0.4293) and
      lower genetic identity (0.6510) were observed between RsB-2 and RsP-4
      combinations. The lowest genetic distance (0.0357) and highest genetic identity
      (0.9650) were found in RsB-1 vs. RsB-2 pair. Thus, RAPD offers a potentially
      simple, rapid and reliable method to evaluate genetic diversity analysis in R.
      solanacearum.

PMID- 26302835
TI  - Susceptibility of 2,252 Pseudomonas aeruginosa Clinical Isolates Over 4 Years to
      9 Antimicrobials in a Tertiary Greek Hospital.
AB  - BACKGROUND: We determined the antimicrobial resistance of and changes over time
      in Pseudomonas aeruginosa isolates from hospitalized patients over the period of
      2010-2013, in relation to the patient setting and clinical specimen origin, in a
      tertiary Greek hospital. METHODS: All P. aeruginosa isolates collected from
      patients with nosocomial infections were processed and cultured according to
      routine methods. The Vitek 2 automated system was used for antimicrobial
      susceptibility testing against 9 antimicrobials. RESULTS: Overall, 2,252 P.
      aeruginosa isolates were tested, and 1,124 (49.91%) were found to be fully
      susceptible. Among 1,128 resistant isolates, 638 (56.56%) were resistant to >=3
      classes of antipseudomonal antibiotics. Intensive care unit isolates were
      significantly more resistant than surgical and medical ward isolates, while blood
      and urine isolates demonstrated the highest resistance rates. Resistance was
      highest in 2012 and lowest in 2013. CONCLUSION: Continuous surveillance of
      antimicrobial resistance is extremely important for controlling P. aeruginosa
      infections in the hospital setting.

PMID- 26302837
TI  - Acute Generalized Exanthematous Pustulosis Caused by Faropenem: A Possible
      Pathogenetic Role for Interleukin-23.

PMID- 26302836
TI  - Evaluation of DOTA-chelated neurotensin analogs with spacer-enhanced biological
      performance for neurotensin-receptor-1-positive tumor targeting.
AB  - INTRODUCTION: Neurotensin receptor 1 (NTR1) is overexpressed in many cancer
      types. Neurotensin (NT), a 13 amino acid peptide, is the native ligand for NTR1
      and exhibits high (nM) affinity to the receptor. Many laboratories have been
      investigating the development of diagnostic and therapeutic radiopharmaceuticals
      for NTR1-positive cancers based on the NT peptide. To improve the biological
      performance for targeting NTR1, we proposed NT analogs with a 1,4,7,10
      tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelation system and
      different lengths of spacers. METHODS: We synthesized four NTR1-targeted
      conjugates with spacer lengths from 0 to 9 atoms (null (N0), beta-Ala-OH (N1), 5
      Ava-OH (N2), and 8-Aoc-OH (N3)) between the DOTA and the pharmacophore. In vitro
      competitive binding, internalization and efflux studies were performed on all
      four NT analogs. Based on these findings, metabolism studies were carried out on
      our best performing conjugate, (177)Lu-N1. Lastly, in vivo biodistribution and
      SPECT/CT imaging studies were performed using (177)Lu-N1 in an HT-29 xenograft
      mouse model. RESULTS: As shown in the competitive binding assays, the NT analogs
      with different spacers (N1, N2 and N3) exhibited lower IC50 values than the NT
      analog without a spacer (N0). Furthermore, N1 revealed higher retention in HT-29
      cells with more rapid internalization and slower efflux than the other NT
      analogs. In vivo biodistribution and SPECT/CT imaging studies of (177)Lu-N1
      demonstrated excellent accumulation (3.1 +/- 0.4%ID/g) in the NTR1-positive
      tumors at 4h post-administration. CONCLUSIONS: The DOTA chelation system
      demonstrated some modest steric inhibition of the pharmacophore. However, the
      insertion of a 4-atom hydrocarbon spacer group restored optimal binding affinity
      of the analog. The in vivo assays indicated that (177)Lu-N1 could be used for
      imaging and radiotherapy of NTR1-positive tumors.

PMID- 26302838
TI  - Cellulose hydrolysis ability of a Clostridium thermocellum cellulosome containing
      small-size scaffolding protein CipA.
AB  - Mutant Clostridium thermocellum YM72 that produces small-size scaffolding protein
      CipA (ssCipA) was isolated from wild-type YM4. Sequencing of ssCipA revealed that
      two domains, cohesin 6 and cohesin 7, were not present. Cellulosome prepared from
      YM72 exhibited a significant reduction of hydrolysis ability on crystalline
      celluloses such as Sigmacell type-20 and cellulose from Halocynthia. To
      investigate this influence in vitro, artificial cellulosomes were assembled as
      recombinant CipA (rCipA) and ssCipA (rssCipA) using native free-cellulosomal
      subunits. The cellulosome assembled using rssCipA showed a 1.8-fold decrease in
      the hydrolysis of crystalline cellulose compared with that of rCipA. However, no
      significant differences in the hydrolysis of carboxymethylcellulose and acid
      swollen cellulose were observed. One protein band was missing from the complex
      that was assembled using rssCipA (confirmed by native-PAGE). The missing protein
      was identified as CelJ, which is a major cellulosomal subunit. This suggests that
      insufficient cooperation of CelJ into the cellulosome results in the significant
      reduction of hydrolysis toward crystalline cellulose. These results indicate that
      cohesin 6 and 7 may be responsible for the cooperation of CelJ through cohesin
      and dockerin interactions, and adequate cooperation of CelJ into the cellulosome
      is important for significant hydrolysis of crystalline cellulose. 

PMID- 26302839
TI  - Improvement of the VEGF binding ability of DNA aptamers through in silico
      maturation and multimerization strategy.
AB  - Aptamers are mainly selected by in vitro selection using random nucleic acid
      libraries. These aptamers have often shown insufficient affinity for biomedical
      applications. We improved DNA aptamer binding affinity for vascular endothelial
      growth factor (VEGF) through in silico maturation (ISM) and aptamer
      multimerization. ISM is one of a number of evolutionary approaches and aptamer
      multimerization is one of several semi-rational strategies to improve function.
      We first reselected VEGF-binding aptamers using a partially randomized DNA
      library and identified two aptamers with higher binding ability than that of a
      known aptamer. We conducted ISM using the re-selected aptamers to optimize the
      key loop sequences created by a three-way junction structure. After five ISM
      rounds, we identified aptamer 2G19 [dissociation constant (Kd), 52 nM] as a local
      optimum of the defined search space. We characterized the aptamer and found that
      a specific stem-loop structure was involved in aptamer VEGF recognition. To
      further improve its affinity for VEGF, we multimerized 2G19 or its stem-loop
      structure. The designed SL5-trivalent aptamer (Kd, 0.37 nM) with three binding
      motifs significantly increased binding affinity, representing a 500-fold
      improvement from systematic evolution of ligands by exponential enrichment
      selected aptamers.

PMID- 26302840
TI  - Improvement of the thermostability and activity of halohydrin dehalogenase from
      Agrobacterium radiobacter AD1 by engineering C-terminal amino acids.
AB  - In the current study, a three-tiered mutagenesis strategy was employed to
      simultaneously improve the thermostability and activity of halohydrin
      dehalogenase from Agrobacterium radiobacter AD1 (HheC) by engineering the last
      ten amino acids (Met245~Glu254) of its C-terminal region. Initially, truncated
      mutagenesis results displayed that C-terminal deletions decreased the
      thermostability and/or activity of HheC. Then ten residues were subjected to
      single-site saturation mutagenesis, resulting in 20 beneficial single-point
      variants related to the thermostability or activity of HheC. The results clearly
      indicated that residues Met252~Glu254 and Trp249 are crucial for regulating
      enzyme thermostability and activity, respectively. Finally, the beneficial
      substitutions were combined using efficient multi-site combinatorial mutagenesis
      approaches, leading to an outstanding variant PX14
      (Trp249Pro/Met252Leu/Pro253Asp), which had a 17.8-fold higher half-life and a 4.0
      fold higher kcat value than that of wild-type HheC. These results indicated that
      the C-terminal residues play an important role in modulating both the
      thermostability and activity of HheC. 

PMID- 26302841
TI  - Mutations in the Flo8 transcription factor contribute to virulence and phenotypic
      traits in Candida albicans strains.
AB  - The ability of Candida albicans to switch between multiple morphological states,
      including yeast (blastospores), fliamentous, pseudohyphal and hyphal forms, has
      been shown to be important for its pathogenicity and virulence. The transcription
      factor Flo8, which contains the LisH domain, is a downstream regulator of the
      cAMP/PKA pathway. Four clinical strains from adult women with recurrent vaginitis
      were isolated, and their morphology was observed. The results showed that two
      strains presented longer hyphal threads, stronger adherence to plastic and
      invasion into agar medium, and one strain was defective in filament and biofilm
      growth. Interestingly, mutations in the FLO8 gene were identified in these
      strains. We analyzed the contribution of these mutants to filamentous growth by
      constructing mutant strains and investigating their morphological and
      ultrastructural characteristics, including putative virulence traits, in vitro
      and in vivo. The results showed that the G723R and T751D Flo8 mutants enhanced
      activation of the Flo8C terminus, thereby promoting filamentous growth and
      increasing virulence. 

PMID- 26302842
TI  - Exploitation of endophytic fungus, Guignardia mangiferae for extracellular
      synthesis of silver nanoparticles and their in vitro biological activities.
AB  - The aim of this study was to synthesize highly biocompatible and functionalized
      silver nanoparticles using endophytic fungi isolated from the leaves of medicinal
      plants. Among 13 fungi tested, the isolate, Guignardia mangiferae (Bios PTK 4)
      extracellularly synthesized well-dispersed and extremely stable silver
      nanoparticles under optimized reaction conditions within 12 h. These
      nanoparticles were characterized by HR-TEM, SAED, XRD and EDX analyses. G.
      mangiferae synthesized 5-30 nm sized, spherical shaped silver nanoparticles.
      Effect of pH on the antibacterial activity of silver nanoparticles was studied
      using well diffusion assay; on the basis of particle stability and antibacterial
      activity, pH 7 was found to be optimum. The leakage of intracellular components
      has clearly demonstrated that silver nanoparticles damage the bacterial cells by
      formation of pores, which affect the membrane permeability and finally leads to
      cell death. In addition, silver nanoparticles exhibited excellent antifungal
      activity against plant pathogenic fungi. Cytotoxic effects of silver
      nanoparticles showed IC50 values of 63.37, 27.54 and 23.84 MUg/mL against normal
      African monkey kidney (Vero), HeLa (cervical) and MCF-7 (breast) cells,
      respectively, at 24 h incubation period. Thus, the obtained results convincingly
      suggest that silver nanoparticles synthesized from G. mangiferae are highly
      biocompatible and have wider applicability and they could be explored as
      promising candidates for a variety of biomedical/pharmaceutical and agricultural
      applications.

PMID- 26302843
TI  - Secreted gingipains from Porphyromonas gingivalis colonies exert potent
      immunomodulatory effects on human gingival fibroblasts.
AB  - Periodontal pathogens, including Porphyromonas gingivalis, can form biofilms in
      dental pockets and cause inflammation, which is one of the underlying mechanisms
      involved in the development of periodontal disease, ultimately leading to tooth
      loss. Although P. gingivalis is protected in the biofilm, it can still cause
      damage and modulate inflammatory responses from the host, through secretion of
      microvesicles containing proteinases. The aim of this study was to evaluate the
      role of cysteine proteinases in P. gingivalis colony growth and development, and
      subsequent immunomodulatory effects on human gingival fibroblast. By comparing
      the wild type W50 with its gingipain deficient strains we show that cysteine
      proteinases are required by P. gingivalis to form morphologically normal
      colonies. The lysine-specific proteinase (Kgp), but not arginine-specific
      proteinases (Rgps), was associated with immunomodulation. P. gingivalis with Kgp
      affected the viability of gingival fibroblasts and modulated host inflammatory
      responses, including induction of TGF-beta1 and suppression of CXCL8 and IL-6
      accumulation. These results suggest that secreted products from P. gingivalis,
      including proteinases, are able to cause damage and significantly modulate the
      levels of inflammatory mediators, independent of a physical host-bacterial
      interaction. This study provides new insight of the pathogenesis of P. gingivalis
      and suggests gingipains as targets for diagnosis and treatment of periodontitis. 

PMID- 26302844
TI  - Probing role of key residues in the divergent evolution of Yarrowia lipolytica
      lipase 2 and Aspergillus niger eruloyl esterase A.
AB  - Yarrowia lipolytica lipase 2 (YLLip2) and Aspergillus niger feruloyl esterase A
      (AnFaeA) are enzymes of similar structures but with different functions. They are
      both classified into the same homologous family in Lipase Engineering Database
      (LED). The major difference between the two enzymes is that YLLip2 exhibits
      interfacial activity while AnFaeA does not. In order to better understand the
      interfacial activation mechanisms of YLLip2, structure guided site-directed
      mutagenesis were performed, mutants were constructed, kinetics parameters and
      lipase properties were detected. Mutant enzymes showed enhanced catalytic
      efficiency towards p-nitrophenyl butyrin (pNPB) but their catalytic efficiency
      decreased towards p-nitrophenyl palmitate (pNPP), their catalysis behavior was
      more close to feruloyl esterase. Moreover, the mutant enzymes exhibited enhanced
      thermostability compared with their wild type. These results indicate that I100
      and F129 are probably cut-off point of divergent functions between the two
      enzymes during evolution. 

PMID- 26302845
TI  - Enhancing the stability and antibiofilm activity of DspB by immobilization on
      carboxymethyl chitosan nanoparticles.
AB  - A beta-N-acetyl-glucosaminidase (DspB) from Aggregatibacter actinomycetemcomitans
      CU1000 has been proved to inhibit and detach the biofilms formed by
      Staphylococcus epidermidis, Staphylococcus aureus and A. actinomycetemcomitans.
      However, the application of this enzyme is limited by its poor stability. In the
      present study, a beta-N-acetyl-glucosaminidase encoding gene, dspB, was cloned
      from A. actinomycetemcomitans HK1651 and expressed in Escherichia coli. The
      recombinant DspB was loaded on hydrogel nanoparticles, which was prepared by
      using linoleic acid (LA) modified carboxymethyl chitosan (CMCS) after sonication.
      The nanoparticles were almost saturated by DspB at 0.3 mg/ml, which gave a
      loading capacity of 76.7%. The immobilization enhanced thermal stability, storage
      stability and reusability of DspB significantly. Moreover, it also increased
      antibiofilm activity due to the dual mechanism, including the improvement of the
      enzyme stability and the antibiofilm activity of CMCS nanoparticles.

PMID- 26302846
TI  - DegQ regulates the production of fengycins and biofilm formation of the
      biocontrol agent Bacillus subtilis NCD-2.
AB  - Bacillus subtilis NCD-2 is an excellent biocontrol agent for tomato gray mold and
      cotton soil-borne diseases. The fengycin lipopeptides serve as a major role in
      its biocontrol ability. A previous study revealed that insertion of degQ with the
      mini-Tn10 transposon decreased the antifungal activity of strain NCD-2 against
      the growth of Botrytis cinerea. To clarify the regulation of degQ on the
      production of fengycin, we deleted degQ by in-frame mutagenesis. Compared with
      the wild-type strain NCD-2, the degQ-null mutant had decreased extracellular
      protease and cellulase activities as well as antifungal ability against the
      growth of B. cinerea in vitro. The lipopeptides from the degQ-null mutant also
      had significantly decreased antifungal activity against B. cinerea in vitro and
      in vivo. This result was confirmed by the decreased fengycin production in the
      degQ-null mutant that was detected by fast protein liquid chromatography
      analysis. Quantitative reverse transcription PCR further demonstrated that degQ
      positively regulated the expression of the fengycin synthetase gene. In addition,
      the degQ-null mutant also had a flatter colony phenotype and significantly
      decreased biofilm formation ability relative to the wild-type strain. All of
      those characteristics from degQ-null mutant could be restored to the strain NCD-2
      wild-type level by complementation of intact degQ in the mutant. Therefore, DegQ
      may be an important regulator of fengycin production and biofilm formation in B.
      subtilis NCD-2. 

PMID- 26302847
TI  - Mitochondrial fission protein MoFis1 mediates conidiation and is required for
      full virulence of the rice blast fungus Magnaporthe oryzae.
AB  - The mitochondrial fission protein Fis1 regulates yeast mitochondrial fission and
      is required for ethanol-induced mitochondrial fragmentation and apoptosis. To
      examine the function of Fis1 in a plant pathogenic fungus, we cloned the MoFIS1
      gene, a homolog of Saccharomyces cerevisiae FIS1, from Magnaporthe oryzae and
      characterized its function by targeted gene deletion and mutant phenotypic
      analysis. MoFIS1 deletion mutants were unaltered in conidial germination,
      appressorium formation, and mating tests, but were severely defective in colony
      growth, conidiation, virulence on rice and barley, growth under nitrogen and
      glucose deficiency, and growth under osmotic stress. Blast lesions on rice leaves
      caused by the DeltaMofis1 strain were significantly reduced, were non
      proliferating, and were less coalesced as compared to the highly coalesced and
      proliferating lesions resulting from infection with the wild-type strain. The
      defects in growth, conidiation, and virulence of the mutant were restored in a
      complementation strain of DeltaMofis1. A MoFis1-GFP fusion protein co-localized
      with Mitotracker red in mitochondria. These results show that MoFIS1 encodes a
      mitochondrial protein that regulates fungal growth, conidiation, and virulence in
      M. oryzae. 

PMID- 26302848
TI  - Broad spectrum antimicrobial compounds from the bacterium Exiguobacterium
      mexicanum MSSRFS9.
AB  - Clinical bacterial pathogens front a major challenge for the clinical researchers
      and physicians. In particular microbial pathogens like Escherichia coli, Shigella
      flexneri, Klebsiella pneumonia and Salmonella enterica are apparelled with
      systemic machineries to bring down the human immune system as well as proliferate
      dramatically in a short period which in turn cause a pronounced ailment to the
      human health. In vitro evaluation of four purified compounds isolated from
      rhizosphere bacterium Exiguobacterium mexicanum tested against clinical pathogens
      mentioned above by disc diffusion method showed the two compounds viz., 3,6,18
      trione, 9,10-dihydro-12'-hydroxyl-2methyl-5-(phenyl methyl) (5'-alpha, 10-alpha)
      dihydroergotamine (C3) and dipropyl - S-propyl ester (C4) exhibit antibacterial
      property against all the tested pathogens. Among the four clinical pathogens
      tested, compound C3 has shown higher zone of inhibition against S. enterica with
      17+/-0 mm, followed by S. flexneri with 16.5+/-0.7 mm, E. coli with 15+/-0 mm and
      K. pneumoniae with 14+/-0 mm, respectively. The compound C4 has shown higher
      antimicrobial activity against S. enterica with 21.5+/-0.7 mm zone of inhibition,
      followed by S. flexneri with 19.5+/-0.7 mm, E. coli with 17+/-0 mm and K.
      pneumoniae with 16+/-0 mm, these two compounds were found to be safer when
      subjected to rat haematological and enzymatic analysis.

PMID- 26302849
TI  - Polymorphisms of PRLHR and HSPA12A and risk of gastric and colorectal cancer in
      the Chinese Han population.
AB  - BACKGROUND: Gastric and colorectal cancers have a major impact on public health,
      and are the most common malignant tumors in China. The aim of this research was
      to study whether polymorphisms of CHCHD3P1-HSP90AB7P, GRID1, HSPA12A, PRLHR,
      SBF2, POLD3 and C11orf93-C11orf92 genes are associated with the risk of gastric
      and colorectal cancers in the Chinese Han population. METHODS: We genotyped seven
      single nucleotide polymorphisms (SNPs) from seven genes. We selected 588 patients
      with gastric cancer and 449 with colorectal cancer, along with 703 healthy
      controls. All these SNPs were evaluated using the chi2 test and genetic model
      analysis. RESULTS: The genotype "A/T" of rs12413624 in PRLHR gene was associated
      with a decreased risk of colorectal cancer in allele model analysis [odds ratio
      (OR) = 0.81; 95% confidence interval (CI) = 0.68-0.97; p = 0.018] and log
      additive model analysis (OR = 0.81; 95% CI = 0.66-0.98; p = 0.032). The genotype
      "A/G" of rs1665650 in HSPA12A gene was associated with a decreased risk of
      gastric cancer in overdominant model analysis (OR = 0.77; 95% CI = 0.60-0.99; p =
      0.038). CONCLUSIONS: Our results provide evidence that variants of PRLHR gene are
      a protective factor in colorectal cancer and variants of HSPA12A gene are a
      protective factor in gastric cancer in the Chinese Han population.

PMID- 26302850
TI  - Vitamin D metabolism in the premature newborn: A randomized trial.
AB  - BACKGROUND & AIMS: Vitamin D status during infancy has been associated with
      important pediatric health outcomes; however concentrations of many vitamin D
      metabolites in premature infants are not yet described. The objective of this
      study was to evaluate concentrations of 25(OH)D3, 24,25(OH)2D3, and 3-epi
      25(OH)D3 in premature infants. METHODS: 32 infants <32 weeks gestation were
      randomized to receive 400 or 800IU/day of vitamin D3 orally. Vitamin D
      metabolites from serum obtained monthly were analyzed in triplicate using a
      novel, very sensitive Liquid Chromatography-Tandem Mass Spectrometry-based
      method. Statistical analysis was conducted using the Fisher's exact test,
      Wilcoxon Rank Sum test, and Spearman correlation coefficients. Measurements over
      time were fit with linear mixed effect models. A p-value of <0.05 was considered
      statistically significant. RESULTS: Mean serum 25(OH)D3 concentrations in cord
      blood were 17.3 ng/mL; mean 3-epi-25(OH)D3 were 1.3 ng/mL, mean 24,25(OH)2D3 were
      1.4 ng/mL. Both 25(OH)D3 and 3-epi-25(OH)D3 increased significantly over time,
      and the percent of total 25(OH)D3 concentration that was 3-epi-25(OH)D3 also
      increased significantly (7.2% vs. 29.7%, p < 0.0001 for cord blood vs. 8 weeks).
      Serum 25(OH)D3:24,25(OH)2D3 ratios at weeks 4 and 8 were higher than ratios
      reported in older children and adults. CONCLUSION: Vitamin D metabolism in
      infants appears to have distinct differences from adults. Vitamin D
      supplementation was effective in raising 25(OH)D3 concentrations; however
      significant increases in 3-epi-25(OH)D3 also occurred. Increased 25(OH)D3:
      24,25(OH)2D3 ratios in premature infants may be due to immature expression of
      CYP24A1. Further work is necessary to determine if there are developmental
      advantages to this unique vitamin D metabolism.

PMID- 26302851
TI  - Immunomodulation and nitric oxide restoration by a probiotic and its activity in
      gut and peritoneal macrophages in diabetic rats.
AB  - BACKGROUND: The hyperglycemia leads to increased oxidative stress, causing lipid
      peroxidation and imbalance in the immune system. AIMS: To investigate the effect
      of Kefir - a probiotic containing different strains - on metabolic parameters,
      cytokines, nitric oxide (NO) production, phagocytic activity of peritoneal
      macrophages and intestinal modulation in diabetes. METHODS: Wistar rats received
      injection of streptozotocin (45 mg/kg, intravenously) and diabetes was defined as
      glycemia >=200 mg/dL. The animals were distributed in four groups: control (CTL);
      control Kefir (CTLK); diabetic (DM); diabetic Kefir (DMK). Kefir was given at 1.8
      mL/day by gavage, started on the 5th day of diabetes, during 8 weeks. The animals
      were allocated in metabolic cages, pre and post treatment with Kefir, for
      measurement of the metabolic parameters, such as water intake, food intake,
      diuresis, glycemia, body mass, insulin and lipid profile, these last two were
      only measured at the end of Kefir protocol. After treatment, the animals were
      euthanized and the peritoneal cavity was prepared, resident macrophages were
      collected and cultured for analysis of the phagocytic activity, cytokines (IL-10,
      TNF-alpha, IL-17, IL-1beta) and NO. The intestinal modulation was performed by
      the quantification of Peyer's patches (PP) in the small intestine. The data were
      presented as mean +/- SEM, with significance of p < 0.05. RESULTS: DM when
      compared to CTL showed increase in water intake (133 +/- 7 vs. 28 +/- 1 mL, p <
      0.0001), food intake (40 +/- 2 vs. 16 +/- 1 g, p < 0.0001), diuresis (102 +/- 5
      vs. 13 +/- 1 mL, p < 0.0001) and glycemia (567 +/- 12 vs. 84 +/- 3 mg/dL, p <
      0.0001), while in DMK group all these metabolic parameters were decreased (96 +/-
      14; 36 +/- 1; 86 +/- 7 and 407 +/- 19, respectively, p < 0.0001), presenting
      increase of body mass (42 +/- 5 vs. 16 +/- 4Delta, p < 0.0001) and insulin levels
      (0.3 +/- 0.8 vs. 0.1 +/- 0.04 ng/mL, p < 0.0001) compared to DM. The lipid
      profile of the diabetic groups showed tendency to increase compared to the
      respective controls. In relation to function of peritoneal macrophages, DMK group
      vs. DM showed improvement in phagocytic capacity (70 +/- 5 vs. 51 +/- 7%, p =
      0,0023) and increased concentration of all the cytokines analyzed (pg/mL), as IL
      10 (926 +/- 69 vs. 556 +/- 92, p = 0.0004), TNF-alpha (178 +/- 20 vs. 109 +/- 20,
      p = 0.005), IL-17 (33 +/- 1 vs. 9 +/- 1, p = 0.0001) and IL-1beta (102 +/- 14 vs.
      70 +/- 5, p = 0.0129), after 24 h of LPS stimulation; including NO
      bioavailability after 24 h (102 +/- 9 vs. 66 +/- 5 MUM/mL, p = 0.0029) or 48 h
      (143 +/- 8 vs. 119 +/- 4 MUM/mL, p = 0.0102) of LPS stimulation. Moreover, the
      number of PP in the whole small intestine of DMK group was also increased as
      compared to DM (22 +/- 1 vs. 18 +/- 1, p = 0.0292). CONCLUSION: These results
      show that Kefir has a potential to modulate the immune response and activate
      peritoneal macrophages in diabetic animals, which suggests that it could enhance
      the immunocompetence of patients affected by diabetes mellitus. The hypoglycemic
      effect of this probiotic could be used as a tool to control glycemia, reducing or
      delaying the onset of complications associated with this disease.

PMID- 26302852
TI  - Low phosphatemia in extremely low birth weight neonates: A risk factor for
      hyperglycemia?
AB  - BACKGROUND & AIMS: Hyperglycemia occurs in more than half of the extremely low
      birth weight (ELBW) neonates during the first weeks of life, and is correlated
      with an increased risk of morbi-mortality. Hypophosphatemia is another frequent
      metabolic disorder in this population. Data from animal, adult studies and
      clinical observation suggest that hypophosphatemia could induce glucose
      intolerance. Our aim was to determine whether a low phosphatemia is associated
      with hyperglycemia in ELBW neonates. METHODS: This observational study included
      ELBW infants admitted in a tertiary neonatal care center (2010-2011). According
      to the center's policy, they received parenteral nutrition from birth and human
      milk from day 1. Phosphatemia and glycemia were measured routinely during
      parenteral nutrition. Hyperglycemia was defined by two consecutives values >8.3
      mmol/L (150 mg/dL). Statistical analysis used a joint model combining a mixed
      effects and a survival submodels to measure the association between phosphate and
      hyperglycemia. RESULTS: The study included 148 patients. Mean gestational
      (Standard Deviation) age was 27.3 (1.6) weeks; mean birth weight was 803 (124)
      grams; 57% presented hyperglycemia. The multivariate joint model showed that the
      hazard of hyperglycemia at a given time was multiplied by 3 for each 0.41 mmol/L
      decrease of phosphate level at this time (p = 0.002) and by 3.85 for the same
      decreased of phosphate the day before (p = 0.0015). CONCLUSION: To our knowledge,
      this is the first study suggesting that low phosphatemia can be associated with
      hyperglycemia in ELBW neonates. Further studies will have to demonstrate whether
      better control of phosphatemia could help in preventing hyperglycemia.

PMID- 26302853
TI  - Estimation of the individual slaughterhouse surveillance sensitivity for bovine
      tuberculosis in Catalonia (North-Eastern Spain).
AB  - The achievement of the Officially Tuberculosis Free (OTF) status in regions with
      low bovine Tuberculosis (bTB) herd prevalence, as is the case of North-Eastern
      Spain (Catalonia), might be a likely option in the medium term. In this context,
      risk-based approaches could be an alternative surveillance strategy to the costly
      current strategy. However, before any change in the system may be contemplated, a
      reliable estimate of the sensitivity of the different surveillance components is
      needed. In this study, we focused on the slaughterhouse component. The
      probability of detection of a bTB-infected cattle by the slaughterhouses in
      Catalonia was estimated as the product of three consecutive probabilities: (P1)
      the probability that a bTB-infected animal arrived at the slaughterhouse
      presenting Macroscopically Detectable Lesions (MDL); (P2) the probability that
      MDL were detected by the routine meat inspection process and (P3) the probability
      that the veterinary officer suspected bTB and sent the sample for laboratory
      confirmation. The first probability was obtained from data collected through the
      bTB eradication program carried out in Catalonia between 2005 and 2008, while the
      last two were obtained through the expert opinion of the veterinary officers
      working at the slaughterhouses who fulfilled a questionnaire administered during
      2014. The bTB surveillance sensitivity of the different cattle slaughterhouses in
      Catalonia obtained in this study was 31.4% (CI 95%: 28.6-36.2), and there were
      important differences among them. The low bTB surveillance sensitivity was mainly
      related with the low probability that a bTB-infected animal arrived at the
      slaughterhouse presenting MDL (around 44.8%). The variability of the sensitivity
      among the different slaughterhouses could be explained by significant
      associations between some variables included in the survey and P2. For instance,
      factors like attendance to training courses, number of meat technicians and speed
      of the slaughter chain were significantly related with the probabilities that a
      MDL was detected by the meat inspection procedure carried out in the
      slaughterhouse. Technical and policy efforts should be focused on the improvement
      of these factors in order to maximize the slaughterhouse sensitivity. 

PMID- 26302854
TI  - Cow-specific risk factors for clinical mastitis in Brazilian dairy cattle.
AB  - Information related to mastitis risk factors is useful for the design and
      implementation of clinical mastitis (CM) control programs. The first objective of
      our study was to model the risk of CM under Brazilian conditions, using cow
      specific risk factors. Our second objective was to explore which risk factors
      were associated with the occurrence of the most common pathogens involved in
      Brazilian CM infections. The analyses were based on 65 months of data from 9,789
      dairy cows and 12,464 CM cases. Cow-specific risk factors that could easily be
      measured in standard Brazilian dairy farms were used in the statistical analyses,
      which included logistic regression and multinomial logistic regression. The first
      month of lactation, high somatic cell count, rainy season and history of clinical
      mastitis cases were factors associated with CM for both primiparous and
      multiparous cows. In addition, parity and breed were also associated risk factors
      for multiparous cows. Of all CM cases, 54% showed positive bacteriological
      culturing results from which 57% were classified as environmental pathogens, with
      a large percentage of coliforms (35%). Coagulase-negative Staphylococcus (16%),
      Streptococcus uberis (9%), Streptococcus agalactiae (7%) and other Streptococci
      (9%) were also common pathogens. Among the pathogens analyzed, the association of
      cow-specific risk factors, such as Zebu breed (OR=5.84, 95%CI 3.77-10.77) and
      accumulated history of SCC (1.76, 95%CI 1.37-2.27), was different for CM caused
      by Coagulase-negative Staphylococcus and S. agalactiae in comparison to CM caused
      by coliforms. Our results suggest that CM control programs in Brazil should
      specially consider the recent history of clinical mastitis cases and the
      beginning of the lactations, mainly during the rainy season as important risk
      factor for mastitis. 

PMID- 26302855
TI  - HIV-1 subtype diversity among clinical specimens submitted for routine antiviral
      drug resistance testing in the United States.
AB  - Diversity of human immunodeficiency virus type 1 (HIV-1) has important
      implications for the diagnosis, treatment, and management of HIV-1-infected
      individuals. HIV-1 pol sequences from 3895 clinical plasma specimens collected in
      the United States over a 1-year period and submitted for routine HIV-1 genotypic
      drug resistance testing were retrospectively analyzed for HIV-1 subtype. Of these
      3895 HIV-1 sequences, 207 (5.31%) were determined to be non-B subtypes (including
      recombinant forms). Among individual states, the percentage of non-B subtypes
      ranged from 0% (12 states) to 28.57% in South Dakota, with 7 states having
      percentages of >10%. All 4 states with the highest percentages of non-B subtypes
      were located within the US West North Central region: Minnesota, 11.82%; Iowa,
      15.38%; North Dakota, 25.00%; and South Dakota, 28.57%. Reasons for the
      unexpectedly wide diversity of HIV-1 subtypes present in multiple states located
      in the West North Central region of the United States remain to be determined. 

PMID- 26302856
TI  - Clinical evaluation of a helicase-dependant amplification (HDA)-based commercial
      assay for the simultaneous detection of HSV-1 and HSV-2.
AB  - In this study, we evaluate the performance of a commercial assay, the AmpliVue
      HSV 1+2 Assay (Quidel), which employs HDA for the detection of both HSV-1 and HSV
      2. The assay was tested on 307 clinical specimens (genital, oral, and dermal).
      When compared to shell vial virus culture and immunofluorescence typing of HSV,
      the positive percent agreement and negative percent agreement values were 98.2%
      and 90.9%, respectively. Excellent assay performance was demonstrated. 

PMID- 26302857
TI  - Particle size tailoring of ursolic acid nanosuspensions for improved anticancer
      activity by controlled antisolvent precipitation.
AB  - The present study was aimed at tailoring the particle size of ursolic acid (UA)
      nanosuspension for improved anticancer activity. UA nanosuspensions were prepared
      by antisolvent precipitation using a four-stream multi-inlet vortex mixer (MIVM)
      under defined conditions of varying solvent composition, drug feeding
      concentration or stream flow rate. The resulting products were characterized for
      particle size and polydispersity. Two of the UA nanosuspensions with mean
      particle sizes of 100 and 300 nm were further assessed for their in-vitro
      activity against MCF-7 breast cancer cells using fluorescence microscopy with
      4',6-diamidino-2-phenylindole (DAPI) staining, as well as flow cytometry with
      propidium (PI) staining and with double staining by fluorescein isothiocyanate.
      It was revealed that the solvent composition, drug feeding concentration and
      stream flow rate were critical parameters for particle size control of the UA
      nanosuspensions generated with the MIVM. Specifically, decreasing the UA feeding
      concentration or increasing the stream flow rate or ethanol content resulted in a
      reduction of particle size. Excellent reproducibility for nanosuspension
      production was demonstrated for the 100 and 300 nm UA preparations with a
      deviation of not more than 5% in particle size from the mean value of three
      independent batches. Fluorescence microscopy and flow cytometry revealed that
      these two different sized UA nanosuspensions, particularly the 300 nm sample,
      exhibited a higher anti-proliferation activity against the MCF-7 cells and
      afforded a larger population of these cells in both early and late apoptotic
      phases. In conclusion, MIVM is a robust and pragmatic tool for tailoring the
      particle size of the UA nanosuspension. Particle size appears to be a critical
      determinant of the anticancer activity of the UA nanoparticles.

PMID- 26302858
TI  - A novel scalable manufacturing process for the production of hydrogel-forming
      microneedle arrays.
AB  - A novel manufacturing process for fabricating microneedle arrays (MN) has been
      designed and evaluated. The prototype is able to successfully produce 14*14 MN
      arrays and is easily capable of scale-up, enabling the transition from laboratory
      to industry and subsequent commercialisation. The method requires the custom
      design of metal MN master templates to produce silicone MN moulds using an
      injection moulding process. The MN arrays produced using this novel method was
      compared with centrifugation, the traditional method of producing aqueous
      hydrogel-forming MN arrays. The results proved that there was negligible
      difference between either methods, with each producing MN arrays with comparable
      quality. Both types of MN arrays can be successfully inserted in a skin simulant.
      In both cases the insertion depth was approximately 60% of the needle length and
      the height reduction after insertion was in both cases approximately 3%. 

PMID- 26302859
TI  - Characterisation of dry powder inhaler formulations using atomic force
      microscopy.
AB  - Inhalation formulations are a popular way of treating the symptoms of respiratory
      diseases. The active pharmaceutical ingredient (API) is delivered directly to the
      site of action within the deep lung using an inhalation device such as the dry
      powder inhaler (DPI). The performance of the formulation and the efficiency of
      the treatment depend on a number of factors including the forces acting between
      the components. In DPI formulations these forces are dominated by
      interparticulate interactions. Research has shown that adhesive and cohesive
      forces depend on a number of particulate properties such as size, surface
      roughness, crystallinity, surface energetics and combinations of these. With
      traditional methods the impact of particulate properties on interparticulate
      forces could be evaluated by examining the bulk properties. Atomic force
      microscopy (AFM), however, enables the determination of local surface
      characteristics and the direct measurement of interparticulate forces using the
      colloidal probe technique. AFM is considered extremely useful for evaluating the
      surface topography of a substrate (an API or carrier particle) and even allows
      the identification of crystal faces, defects and polymorphs from high-resolution
      images. Additionally, information is given about local mechanical properties of
      the particles and changes in surface composition and energetics. The assessment
      of attractive forces between two bodies is possible by using colloidal probe AFM.
      This review article summarises the application of AFM in DPI formulations while
      specifically focussing on the colloidal probe technique and the evaluation of
      interparticulate forces. 

PMID- 26302860
TI  - Nanoliposome-mediated targeting of antibodies to tumors: IVIG antibodies as a
      model.
AB  - Monoclonal antibodies are routinely used as tools in immunotherapies against
      solid tumors. However, administration of monoclonal antibodies may cause
      undesired side effects due to their accumulation in non-targeted organs.
      Nanoliposomes of less than 200 nm can target antibodies to tumors by enhanced
      permeation and retention (EPR) mechanisms. To direct monoclonal antibodies to
      tumors, nanoliposomes encapsulating intravenous immunoglobulin (IVIG) as a model
      antibody were prepared. The liposomes had average diameters of 100 nm and
      encapsulation efficiencies of 31 to 46%. They showed less than 10% release in
      plasma at 37 degrees C up to seven days. The secondary and tertiary structures of
      liposome-encapsulated antibodies were analyzed by circular dichroism (CD)
      spectroscopy. The near and far-UV spectra analyses revealed no obvious
      conformational changes in the structures of the encapsulated antibodies. The
      biodistribution of free and liposome-encapsulated iodinated antibodies was
      investigated in mice bearing C-26 colon carcinoma tumors. The accumulation of
      liposome-encapsulated antibodies in tumors was significantly greater than that of
      free antibodies due to the EPR effect. The PEGylated liposomes were more
      efficient in the delivery of antibodies to the tumor site than non-PEGylated
      liposomes. We conclude that administration of monoclonal antibodies in PEGylated
      liposomes is more efficient than administration of non-encapsulated monoclonal
      antibodies for solid tumor immunotherapy.

PMID- 26302861
TI  - Manipulation of lysozyme phase behavior by additives as function of
      conformational stability.
AB  - Undesired protein aggregation in general and non-native protein aggregation in
      particular need to be inhibited during bio-pharmaceutical processing to ensure
      patient safety and to maintain product activity. In this work the potency of
      different additives, namely glycerol, PEG 1000, and glycine, to prevent lysozyme
      aggregation and selectively manipulate lysozyme phase behavior was investigated.
      The results revealed a strong pH dependency of the additive impact on lysozyme
      phase behavior, lysozyme solubility, crystal size and morphology. This work aims
      to link this pH dependent impact to a protein-specific parameter, the
      conformational stability of lysozyme. At pH 3 the addition of 10% (w/v) glycerol,
      10% (w/v) PEG 1000, and 1 M glycine stabilized or destabilized lysozymes' native
      conformation resulting in a modified size of the crystallization area without
      influencing lysozyme solubility, crystal size and morphology. Addition of 1 M
      glycine even promoted non-native aggregation at pH 3 whereas addition of PEG 1000
      completely inhibited non-native aggregation. At pH 5 the addition of 10% (w/v)
      glycerol, 10% (w/v) PEG 1000, and 1 M glycine did not influence lysozymes' native
      conformation, but strongly influenced the position of the crystallization area,
      lysozyme solubility, crystal size and morphology. The observed pH dependent
      impact of the additives could be linked to a differing lysozyme conformational
      stability in the binary systems without additives at pH 3 and pH 5. However, in
      any case lysozyme phase behavior could selectively be manipulated by addition of
      glycerol, PEG 1000 and glycine. Furthermore, at pH 5 crystal size and morphology
      could selectively be manipulated.

PMID- 26302862
TI  - Solvent exchange-induced in situ forming gel comprising ethyl cellulose
      antimicrobial drugs.
AB  - Solvent-exchanged in situ forming gel is a drug delivery system which is in sol
      form before administration. When it contacts with the body fluid, then the water
      miscible organic solvent dissipates and water penetrates into the system, leading
      the polymer precipitation as in situ gel at the site of injection. The aim of
      this research was to study the parameters affecting the gel properties, drug
      release and antimicrobial activities of the in situ forming gels prepared from
      ethyl cellulose (EC) dissolved in N-methyl pyrrolidone (NMP) to deliver the
      antimicrobial agents (doxycycline hyclate, metronidazole and benzyl peroxide) for
      periodontitis treatment. The gel appearance, pH, viscosity, rheology,
      syringeability, gel formation, rate of water diffusion into the gels, in vitro
      degradation, drug release behavior and antimicrobial activities against
      Staphylococcus aureus, Escherichia coli, Candida albicans, Streptococcus mutans
      and Porphyrommonas gingivalis were determined. Increasing the amount of EC
      increased the viscosity of system while still exhibiting Newtonian flow and
      increased the work of syringeability whereas decreased the releasing of drug. The
      system transformed into the rigid gel formation after being injected into the
      simulated gingival crevicular fluid. The developed systems containing 5% w/w
      antimicrobial agent showed the antimicrobial activities against all test
      bacteria. Thus the developed solvent exchange-induced in situ forming gels
      comprising EC-antimicrobial drugs exhibited potential use for periodontitis
      treatment. 

PMID- 26302863
TI  - Exploring diagnostic potentials of radioiodinated sennidin A in rat model of
      reperfused myocardial infarction.
AB  - Non-invasive "hot spot imaging" and localization of necrotic tissue may be
      helpful for definitive diagnosis of myocardial viability, which is essential for
      clinical management of ischemic heart disease. We labeled Sennidin A (SA), a
      naturally occurring median dianthrone compound, with (131)I and evaluated (131)I
      SA as a potential necrosis-avid diagnostic tracer agent in rat model of
      reperfused myocardial infarction. Magnetic resonance imaging (MRI) was performed
      to determine the location and dimension of infarction. (131)I-SA was evaluated in
      rat model of 24-hour old reperfused myocardial infarction using single-photon
      emission computed tomography/computed tomography (SPECT/CT), biodistribution,
      triphenyltetrazolium chloride (TTC) histochemical staining, serial sectional
      autoradiography and microscopy. Gamma counting revealed high uptake and prolonged
      retention of (131)I SA in necrotic myocardium and fast clearance from non
      targeted tissues. On SPECT/CT images, myocardial infarction was persistently
      visualized as well-defined hotspots over 24h, which was confirmed by perfect
      matches of images from post-mortem TTC staining and autoradiography.
      Radioactivity concentration in infarcted myocardium was over 9 times higher than
      that of the normal myocardium at 24h. With favorable hydrophilicity and
      stability, radioiodinated SA may serve as a necrosis-avid diagnostic agent for
      assessment of myocardial viability. 

PMID- 26302864
TI  - Natural History of Idiopathic Epiretinal Membrane in Eyes with Good Vision
      Assessed by Spectral-Domain Optical Coherence Tomography.
AB  - PURPOSE: To investigate the natural history of idiopathic epiretinal membrane
      (ERM) in eyes with good visual function using optical coherence tomography (OCT).
      METHODS: Sixty-two eyes of 58 patients with idiopathic ERM, visual acuity of
      20/40 or better, and no significant metamorphopsia were included. The best
      corrected visual acuity (BCVA), central macular thickness (CMT), membrane
      configuration, and ellipsoid zone signal data over 24 months were retrospectively
      analyzed. Based on OCT findings, ERM configurations were categorized as global
      attachment (GA), partial attachment (PA), pseudohole, and vitreomacular traction
      (VMT). RESULTS: The mean BCVA and CMT did not change significantly between
      baseline and 24 months. GA, PA, pseudohole, and VMT types were observed in 33,
      19, 9, and 1 eye at baseline, and in 20, 22, 10, and 1 eye at 24 months,
      respectively. A membrane configuration change was noted in 24 eyes (38.7%) during
      follow-up, and the distribution shifted from GA to the other types (p < 0.001).
      Six eyes had visual loss due to membrane progression, and 4 eyes had spontaneous
      membrane separation. Of the 10 eyes with progression or separation, 6 were of the
      PA type. CONCLUSIONS: Although the BCVA remains stable over 2 years in most
      idiopathic ERM eyes with good visual function at baseline, the membrane
      configuration may change, affecting visual acuity. The GA type would be an early
      stage, and the PA type is prone to changes in visual acuity.

PMID- 26302865
TI  - Constrictive pericarditis complicating cardiac transplantation.
AB  - Constrictive pericarditis is a disease characterized by progressive pericardial
      fibrosis. If left untreated it can lead to progressive heart failure and can be
      severely disabling. Medical management with non-steroidal anti-inflammatory drugs
      in combination with colchicine is promising in the acute phase of the disease but
      for more chronic cases pericardiectomy offers the best chance for hemodynamic
      recovery. Constrictive pericarditis after cardiac transplantation is a rare
      phenomenon. Current literature suggests that early pericardiectomy may be the
      most effective treatment in this subset of patients as well. 

PMID- 26302866
TI  - CYP3A5 mediates bioactivation and cytotoxicity of tetrandrine.
AB  - Tetrandrine is a diaryl ether-type bisbenzylisoquinoline alkaloid and has shown
      multiple pharmacological activities. Our early work demonstrated that tetrandrine
      produced acute pulmonary toxicity and that tetrandrine was biotransformed to a
      quinone methide-derived metabolite mediated by CYP3A enzymes. The formation of
      the reactive intermediate is suggested to be responsible for the pulmonary
      toxicity induced by tetrandrine. In the present study, a WI-38-based Cyp3a5
      transgenic cell line (WI-38/Cyp3a5) was established to investigate the role of
      CYP3A5 in tetrandrine-induced cytotoxicity. The transgenic cells were found to be
      more susceptible to the cytotoxicity of tetrandrine than the wild-type cells (WI
      38/Vector). WI-38/Cyp3a5 cells showed higher cellular ROS levels, higher LDH
      activities in culture media, but lower cellular GSH contents than those observed
      in WI-38/Vector cells after exposure to tetrandrine. And severer apoptosis were
      observed in WI-38/Cyp3a5 cells after treatment with tetrandrine: WI-38/Cyp3a5
      cells had higher proportion of early and late apoptotic cells, higher expression
      levels of caspase-3, but lower level of Bcl-2 than WI-38/Vector cells. This study
      provided strong evidence that CYP3A5 participated in tetrandrine-induced
      cytotoxicity. 

PMID- 26302867
TI  - Hexabromocyclododecane and tetrabromobisphenol A alter secretion of interferon
      gamma (IFN-gamma) from human immune cells.
AB  - Hexabromocyclododecane (HBCD) and tetrabromobisphenol A (TBBPA) are brominated
      flame-retardant compounds used in a variety of applications including insulation,
      upholstery, and epoxy resin circuit boards. Interferon gamma (IFN-gamma) is an
      inflammatory cytokine produced by activated T and NK cells that regulates immune
      responsiveness. HBCD and TBBPA are found in human blood, and previous studies
      have shown that they alter the ability of human natural killer (NK) lymphocytes
      to destroy tumor cells. This study examines whether HBCD and TBBPA affect the
      secretion of IFN-gamma from increasingly complex preparations of human immune
      cells-purified NK cells, monocyte-depleted (MD) peripheral blood mononuclear
      cells (PBMCs), and PBMCs. Both HBCD and TBBPA were tested at concentrations
      ranging from 0.05 to 5 uM. HBCD generally caused increases in IFN-gamma secretion
      after 24-h, 48-h, and 6-day exposures in each of the different cell preparations.
      The specific concentration of HBCD that caused increases as well as the magnitude
      of the increase varied from donor to donor. In contrast, TBBPA tended to decrease
      secretion of IFN-gamma from NK cells, MD-PBMCs, and PBMCs. Thus, exposure to
      these compounds may potentially disrupt the immune regulation mediated by IFN
      gamma. Signaling pathways that have the capacity to regulate IFN-gamma production
      (nuclear factor kappa B (NF-kappaB), p44/42, p38, JNK) were examined for their
      role in the HBCD-induced increases in IFN-gamma. Results showed that the p44/42
      (ERK1/2) MAPK pathway appears to be important in HBCD-induced increases in IFN
      gamma secretion from human immune cells. 

PMID- 26302868
TI  - Histone demethylase JMJD3 is required for osteoblast differentiation in mice.
AB  - JMJD3 (KDM6B) is an H3K27me3 demethylases and emerges as an important player in
      developmental processes. Although some evidence indicated the involvement of
      JMJD3 in osteoblast differentiation in vitro, its role as a whole in osteoblast
      differentiation and bone formation in vivo remains unknown. Here we showed that
      homozygous deletion of Jmjd3 resulted in severe delay of osteoblast
      differentiation and bone ossification in mice. By biochemical and genetical
      methods, we demonstrated that JMJD3 mediated RUNX2 transcriptional activity and
      cooperated with RUNX2 to promote osteoblast differentiation and bone formation in
      vivo. These results strongly demonstrated that JMJD3 is required for osteoblast
      differentiation and bone formation in mice. 

PMID- 26302871
TI  - Undoped accumulation-mode Si/SiGe quantum dots.
AB  - We report on a quantum dot device design that combines the low disorder
      properties of undoped SiGe heterostructure materials with an overlapping gate
      stack in which each electrostatic gate has a dominant and unique function-control
      of individual quantum dot occupancies and of lateral tunneling into and between
      dots. Control of the tunneling rate between a dot and an electron bath is
      demonstrated over more than nine orders of magnitude and independently confirmed
      by direct measurement within the bandwidth of our amplifiers. The inter-dot
      tunnel coupling at the [Formula: see text] charge configuration anti-crossing is
      directly measured to quantify the control of a single inter-dot tunnel barrier
      gate. A simple exponential dependence is sufficient to describe each of these
      tunneling processes as a function of the controlling gate voltage. 

PMID- 26302869
TI  - EARLIER: an observational study to evaluate the use of cinacalcet in incident
      hemodialysis patients with secondary hyperparathyroidism in daily clinical
      practice.
AB  - The EARLIER (Evaluation of MimpARa in incident hemodiaLysis patIEnts with
      secondaRy hyperparathyroidism; SHPT) observational postmarketing surveillance
      study evaluated incident hemodialysis patients (< 1 year dialysis vintage; n =
      146) receiving cinacalcet in Austrian clinical practice. Despite intervention
      with vitamin D sterols and phosphate binders, 24 % had already developed severe
      SHPT (intact parathyroid hormone (iPTH) > 800 pg/mL) at baseline. After
      cinacalcet was started, median iPTH decreased substantially, from 611 pg/mL to
      251 pg/mL (median decrease 58 % [IQR - 36 to - 78 %] at 12 months. Overall, 36 %
      of patients achieved the Kidney Disease Outcomes Quality Initiative (K/DOQI)
      target range (150-300 pg/mL) for iPTH; this included 35 % of those with severe
      SHPT at baseline. Serum phosphorus (P), calcium (Ca) (corr), and Ca (corr) * P
      also decreased, with 43, 34, and 62 % of patients, respectively, reaching K/DOQI
      targets at 12 months. Thus, in this observational study, mineral metabolism in
      incident dialysis patients with SHPT improved after starting cinacalcet. 

PMID- 26302870
TI  - Styrene-maleic acid-copolymer conjugated zinc protoporphyrin as a candidate drug
      for tumor-targeted therapy and imaging.
AB  - Previous studies indicated the potential of zinc protoporphyrin (ZnPP) as an
      antitumor agent targeting to the tumor survival factor heme oxygenase-1, and/or
      for photodynamic therapy (PDT). In this study, to achieve tumor-targeted
      delivery, styrene-maleic acid-copolymer conjugated ZnPP (SMA-ZnPP) was
      synthesized via amide bond, which showed good water solubility, having ZnPP
      loading of 15%. More importantly, it forms micelles in aqueous solution with a
      mean particle size of 111.6 nm, whereas it has an apparent Mw of 65 kDa. This
      micelle formation was not detracted by serum albumin, suggesting it is stable in
      circulation. Further SMA-ZnPP conjugate will behave as an albumin complex in
      blood with much larger size (235 kDa) by virtue of the albumin binding property
      of SMA. Consequently, SMA-ZnPP conjugate exhibited prolonged circulating
      retention and preferential tumor accumulation by taking advantage of enhanced
      permeability and retention (EPR) effect. Clear tumor imaging was thus achieved by
      detecting the fluorescence of ZnPP. In addition, the cytotoxicity and PDT effect
      of SMA-ZnPP conjugate was confirmed in human cervical cancer HeLa cells. Light
      irradiation remarkably increased the cytotoxicity (IC50, from 33 to 5 MUM). These
      findings may provide new options and knowledge for developing ZnPP based
      anticancer theranostic drugs. 

PMID- 26302872
TI  - Antiperistaltic Side-to-Side Ileorectal Anastomosis is Associated with a Better
      Short-Term Fecal Continence and Quality of Life in Slow Transit Constipation
      Patients.
AB  - BACKGROUND: Surgical treatment of refractory slow transit constipation (STC) is
      traditionally performed using end-to-side ileorectal anastomosis (SE-IRA) with
      total abdominal colectomy (TAC). Antiperistaltic side-to-side (SS) IRA is
      suggested to be a superior approach. Employing a well-characterized cohort of STC
      patients, we compared the postoperative outcomes of the 2 surgical approaches.
      METHODS: A total of 42 patients underwent TAC for refractory idiopathic STC.
      Twenty patients were treated using traditional SE-IRA whereas 22 patients were
      treated using SS-IRA. Patients were evaluated at 3 and 6 months as well as at 1
      and 2 years after surgery. Both groups were compared for patient characteristics,
      perioperative data and quality of life. Cleveland Clinic Incontinence Score
      (CCIS) and Gastrointestinal Quality of Life Index (GQILI) were adopted for
      evaluating postoperative recovery. RESULTS: Both study groups were comparable
      with respect to general patient characteristics, disease severity and post
      operative complications. Fewer than 30% of all patients reported substantial
      dissatisfaction with surgical outcomes in both the groups. The SS-IRA group was
      associated with a lower postoperative CCIS (p < 0.05) and a better GQILI (p <
      0.05) than that of the SE-IRA group during early follow-up examinations.
      CONCLUSION: In this study, SS-IRA was superior to traditional SE-IRA for the
      treatment of STC with respect to post-operative outcomes, and especially during
      early follow-up.

PMID- 26302873
TI  - New Strategies in the Prevention of Actinic Keratosis: A Critical Review.
AB  - Actinic keratosis (AK) or lesions of epidermal dysplasia occurring in skin
      chronically exposed to solar radiation is very prevalent in lighter skin persons,
      with chronic long-term sun exposure being the major risk factor. With an aging
      population it is expected that the prevalence of AK will further increase. AK can
      progress to nonmelanoma skin cancer (NMSC) and is a public health concern. Six
      leading dermatologists with expertise in AK and NMSC from Germany met to discuss
      the nature of the disease and the prevention and treatment strategies available
      to dermatologists today. While cosmetic sunscreen products form an essential
      element of sun protection strategies, they are not adequate when damage has
      already been inflicted. Newly developed products of the medical device category
      offer DNA repair function paired with high sun protection factor (SPF) UV
      protection. An adjuvant treatment algorithm for various risk levels of AK was
      developed. For patients with low and moderate risk, sunscreen only is
      recommended. For patient groups with high and very high risk, a very high
      photoprotection and photorepair action (DNA repair enzymes) in medical device
      products all year round is recommended. 

PMID- 26302874
TI  - Identification of a novel HLA-C*15 allele, HLA-C*15:96Q.
AB  - HLA-C*15:96Q differs from C*15:02:01:01 by a single-nucleotide substitution at
      position 164 of exon 3. 

PMID- 26302875
TI  - Risk Factors for Lymph Node Metastasis in Early Gastric Cancer with Signet Ring
      Cell Carcinoma.
AB  - BACKGROUND: Gastrectomy was reported to be an excessive approach for early
      gastric cancer with signet ring cell carcinoma. This study was conducted to
      explore the feasibility of endoscopic submucosal dissection for early gastric
      with signet ring cell carcinoma. METHODS: Data from 1067 patients who underwent
      gastrectomy for early gastric cancer were collected retrospectively. The
      association between the clinicopathological factors and the lymph node metastasis
      was analyzed by univariate and multivariate logistic regression analyses.
      RESULTS: Lymph node metastasis was confirmed in 17.2 % (184/1067) of patients.
      Meanwhile, the incidence of lymph node metastasis with each histology type was
      13.1 % (26/198), 9.8 % (34/347), and 23.8 % (124/522) for signet ring cell
      carcinoma, differentiated carcinomas, and undifferentiated carcinomas,
      respectively. Signet ring cell carcinoma occurs more in women and young patients,
      with a higher predominance for mucosa. Various factors-including sex, tumor size,
      depth of tumor, and lymphovascular invasion-were found to be associated with
      lymph node metastasis for signet ring cell carcinoma (P < 0.05). Multivariate
      analysis revealed that tumor size (7.489, 95 % CI 2.025-27.701) and
      lymphovascular invasion (18.434, 95 % CI 3.256-104.359) were independent risk
      factors for lymph node metastasis (P < 0.05). Further analysis reveals there was
      no positive lymph node in patients with signet ring cell carcinoma when tumor
      confined to mucosa, size <=2 cm and without lymphovascular invasion and
      ulceration. CONCLUSIONS: Given the low risk of lymph node involvement, we
      recommend that endoscopic submucosal dissection be safely applied for early
      gastric signet ring cell carcinoma when tumor confined to mucosa, size <=2 cm,
      and without lymphovascular invasion and ulceration.

PMID- 26302876
TI  - Surgical Management of Caroli's Disease: Single Center Experience and Review of
      the Literature.
AB  - BACKGROUND: Caroli's disease is a rare congenital condition characterized by non
      obstructive dilatation of intrahepatic ducts. In Caroli's syndrome, there is
      additionally an associated congenital hepatic fibrosis. METHODS: With
      institutional review board approval, we identified all patients with Caroli's
      disease and syndrome. RESULTS: Nine patients were identified, seven males and two
      females, with a median age of 40 years. Final pathological diagnoses included
      Caroli's disease (n = 6) and Caroli's syndrome (n = 3). Patients presented with
      deranged liver function, cholangitis, cholangiocarcinoma, abdominal pain,
      cirrhosis, or were diagnosed incidentally. Four patients underwent resection and
      two underwent liver transplantation. Of the resection group, two patients
      subsequently underwent transplantation for recurrent cholangitis due to
      anastomotic stricture in one patient and for end-stage liver disease in the
      other. All patients with Caroli's syndrome underwent liver transplantation. Three
      patients died during follow-up at 26.2, 7.8, and 3 months post-diagnosis with
      recurrence of cholangiocarcinoma, liver failure, and metastatic
      cholangiocarcinoma, respectively. Six patients are alive with a median follow-up
      of 60 months since presentation (range = 10-134 months). CONCLUSIONS: Caroli's
      disease and syndrome have a varied presentation. Most individuals with Caroli's
      disease may be adequately treated by resection, but transplantation is required
      for Caroli's syndrome patients due to the associated hepatic fibrosis.

PMID- 26302877
TI  - Postoperative Omental Infarct After Distal Pancreatectomy: Appearance, Etiology
      Management, and Review of Literature.
AB  - INTRODUCTION: The clinico-radiological characteristics and the natural history of
      postoperative omental infarct (OI) in patients who underwent distal
      pancreatectomy (DP) and splenectomy have not been defined. MATERIALS AND METHODS:
      Twelve patients who underwent DP over a period of 2 years and were
      postoperatively diagnosed with OI based on computed tomography (CT) findings were
      identified. RESULTS: A total of 12 patients were diagnosed with an OI based on
      their postoperative imaging. Seven (58.3 %) patients had previously undergone
      laparoscopic DP, one (8.3 %) had undergone a robotic DP, and in one (8.3 %), a
      laparoscopic DP was converted to an open procedure. The remaining three (25.1 %)
      were treated with open DP. In five (41.6 %) patients, the diagnosis of OI was
      made during routine follow-up. One patient underwent surgical resection of OI,
      and two had drains placed in the mass. Nine patients were managed conservatively.
      During the study period, on review of CT imaging, the minimum prevalence of
      postoperative OI after DP was found to be 22.8 %. A review of literature
      identified nine articles that reported a total of 34 patients who were diagnosed
      with OI after abdominal surgery. CONCLUSION: The management of an asymptomatic
      postoperative OI should be conservative while an early invasive intervention
      should be performed in patients who are symptomatic or have infected OI.

PMID- 26302878
TI  - Hand-Assisted Laparoscopic Approach in Colon Surgery.
AB  - BACKGROUND: This study sought to compare outcomes of patients who underwent hand
      assisted laparoscopic (HAL) colectomy with open and laparoscopic colectomy (LP).
      STUDY DESIGN: The NSQIP databases were used to examine the clinical data of
      patients who underwent elective colectomy during 2012-2013. Multivariate
      regression analysis was performed to compare the three surgical approaches.
      RESULTS: We sampled a total of 21,090 patients who underwent colectomy. Of these,
      7480 (35.5 %) had open colectomy (OC), 8751 (41.5 %) had a laparoscopic
      colectomy, 2860 (13.6 %) had a HAL colectomy, and 1999 (9.5 %) had an open
      procedure converted from LC or HAL. Multivariate regression analysis revealed HAL
      colectomy had a similar mortality (AOR 0.53, P = 0.07) and a lower morbidity (AOR
      0.37, P < 0.01) compared to OC. LC had lower mortality (AOR 0.58, P = 0.02) and
      morbidity (AOR 0.43, P < 0.01) compared to OC. Mortality of patients who
      underwent HAL was not significantly different from LC (AOR 0.90, P = 0.79);
      however, morbidity of such patients was significantly higher than for patients
      who underwent LC (AOR 1.29, P < 0.01). CONCLUSIONS: HAL colectomy is a safe
      approach with significant advantages compared to open colectomy. Although the
      morbidity of patients who underwent HAL is higher than patients who underwent LC,
      the morbidity rate is still lower than OC.

PMID- 26302879
TI  - Octreotide Does Not Prevent Pancreatic Fistula Following Pancreatoduodenectomy in
      Patients with Soft Pancreas and Non-dilated Duct: A Prospective Randomized
      Controlled Trial.
AB  - BACKGROUND: Whether octreotide prevents pancreatic fistula following
      pancreatoduodenectomy is controversial and it is believed to be beneficial in
      soft glands and normal-sized ducts. The aim of this study is to assess the
      potential value of octreotide in reducing the incidence of pancreatic fistula,
      postoperative complications, morbidity and hospital stay in patients with soft
      pancreas and non-dilated ducts. METHODS: A total of 109 patients undergoing
      elective pancreatoduodenectomy with soft pancreas and non-dilated duct were
      randomized to octreotide group versus no octreotide-the control group. Surgical
      steps were standardized and incidences of pancreatic fistula, complications,
      death and hospital stay were assessed. RESULTS: There were 55 patients in
      octreotide group and 54 in the control group. Demographic features and pancreatic
      duct diameter of the groups were comparable. The rates of clinically significant
      pancreatic fistulae (grades B and C) were 10.9 and 18.5 % (p = ns), and morbidity
      was 18 and 29.6 % (p = ns), respectively. Patients who received octreotide
      resumed oral diet early and had a shorter hospital stay. CONCLUSION: This study
      demonstrated no statistical difference in pancreatic fistulae with the use of
      octreotide, though there was a trend towards fewer incidences of pancreatic
      fistulae, morbidity and shorter hospital stay. ClinicalTrials.gov Identifier:
      NCT01301222.

PMID- 26302880
TI  - Strong evidence of sexual dimorphic effect of adiposity excess on insulin
      sensitivity.
AB  - AIMS: Our aims were to investigate in several large samples, with a wide range of
      adiposity, whether: (1) the effect of BMI on insulin sensitivity is different
      between sexes; (2) also waist circumference plays a sex-specific role on insulin
      sensitivity; and (3) serum adiponectin and resistin are mediators of such sex
      dimorphic effect. METHODS: Samples used were: Gargano study 1 (GS1), GS2 and
      Catania study (CS) comprising 3274 individuals. Adiponectin and resistin were
      measured by ELISA. Associations between variables were tested by linear models.
      RESULTS: In all samples, relationship between BMI and HOMAIR was steeper in males
      than in females (BMI-by-sex interaction p = 0.04-0.0007). No interaction was
      observed on serum adiponectin and resistin (p = 0.40-059), which are therefore
      unlikely to mediate the sex-dimorphic effect of BMI on insulin resistance.
      Relationship between waist circumference and HOMAIR was similar between sexes in
      GS1 and GS2 but not in CS (waist-by-sex interaction p = 0.01), comprising much
      heavier individuals. This suggests that a sex-dimorphic effect of abdominal
      adiposity on insulin resistance is observable only in the context of high BMI.
      CONCLUSIONS: Our findings represent a proof of concept that BMI and insulin
      sensitivity are associated in a sex-specific manner. This may explain why females
      are protected from diabetes and cardiovascular disease, compared to males of
      similar BMI.

PMID- 26302881
TI  - Effects of resistance training with moderate vs heavy loads on muscle mass and
      strength in the elderly: A meta-analysis.
AB  - The purpose of the present study was to perform a meta-analysis to compare the
      efficacy of heavy (~80% of one repetition maximum, 1RM) vs light-moderate load
      (~45% 1RM) resistance training (RT) programs in inducing strength gains and
      skeletal muscle hypertrophy in elderly people. To assess the role of training
      volumes, studies in which training protocols were matched for mechanical work
      were independently analyzed. In all 15 studies included (448 subjects, age 67.8
      years), when comparing heavy with light-moderate loads, strength gains tended to
      be larger following RT with higher intensities of load, with the resulting total
      population effect being MU = 0.430 (P = 0.060). Effect sizes were substantially
      smaller in "work-matched" studies (MU = 0.297, P = 0.003). Training with higher
      loads also provoked marginally larger gains in muscle size, although the degree
      of training-induced muscle hypertrophy was generally small (0.056 < MU < 0.136).
      To conclude, provided a sufficient number of repetitions is performed, RT at
      lower than traditionally recommended intensities of load may suffice to induce
      substantial gains in muscle strength in elderly cohorts. 

PMID- 26302882
TI  - Effect of sodium acetate on the adhesion to porcine gastric mucin in a
      Lactococcus lactis strain grown on fructose.
AB  - The association of lactic acid bacteria with mucosal surfaces plays important
      roles in the beneficial effects of these bacteria on human health, such as
      colonization of the gastrointestinal tract for pathogen antagonism. Previously,
      we found that the adhesion of Lactococcus lactis 7-1 to porcine gastric mucin was
      higher with fructose than with lactose, galactose or xylose as the carbon source.
      In this study, we examined the effect of growth conditions on the adhesion of
      strain 7-1 grown on fructose. Medium components affect the adhesion: the adhesion
      of strain 7-1 grown with sodium acetate was higher than that without it. The
      enhancement of adhesion by sodium acetate was not observed under aerobic
      conditions. Cellular properties grown with or without sodium acetate were
      characterized: strain 7-1 grown with sodium acetate had similar sugar contents,
      and different fatty acid composition to those grown without it. Strain 7-1 grown
      with sodium acetate showed significantly lower cell yield and significantly
      higher hydrophobicity than those grown without it, which is associated with
      higher adhesion. Fructose and sodium acetate are frequently used in the food
      industry; this study may reveal a simple way to enhance the adhesion of lactic
      acid bacteria by growing them with these substances. 

PMID- 26302883
TI  - The development of precision medicine in clinical practice.
AB  - Precision medicine allows a dramatic expansion of biological data, while there is
      still an urgent need to understand and insight the exact meaning of those data to
      human health and disease. This has led to an increasing wealth of data
      unanalyzed. The concept of precision medicine is about the customization of
      healthcare, with decisions and practices tailored to an individual patient based
      on their intrinsic biology in addition to clinical "signs and symptoms".
      Construction of a standardized model for the integration of data from various
      platforms is the central mission of the 'New Disease Management Model'. The model
      is helpful for the development of new taxonomy of diseases and subtypes, to
      personalize therapy based on patient genetic profiles. A rapid progression of
      precision therapy has been made recently. Clinical trials have shown the
      therapeutic efficacy of discovered and developed therapeutic agents has improved.
      However, next-generation drugs would be designed for disease subtypes with more
      specificity, efficacy and lower toxicity. 

PMID- 26302884
TI  - Association between serum folic acid level and erectile dysfunction.
AB  - This study measured the serum folic acid (FA) level in patients with erectile
      dysfunction (ED) and evaluated the possible association between the serum FA
      level and erectile function. The study divided 120 patients with ED into 3 groups
      of 40 patients each: those with severe, moderate and mild ED. Forty healthy men
      served as controls. Fasting serum samples were obtained, and the total
      testosterone, cholesterol and FA levels were measured using chemiluminescent
      immunoassays. There were no significant differences in the mean age, mean body
      mass index or mean serum total testosterone and cholesterol levels among the
      three ED groups and controls (P > 0.05). The mean serum FA concentrations were
      7.2 +/- 3.7, 7.1 +/- 3.2, 10.2 +/- 4.6 and 10.7 +/- 4.6 ng ml(-1) in the severe,
      moderate and mild ED and control groups respectively. The mean serum FA
      concentration was significantly higher in the control group than in the severe
      and moderate ED groups (both P < 0.001), but not the mild ED group (P = 0.95).
      Considering the significant differences in the serum FA levels between the
      control and ED groups, serum FA deficiency might reflect the severity of ED. 

PMID- 26302885
TI  - Carbohydrate mouth rinse enhances time to exhaustion during treadmill exercise.
AB  - Mouth rinsing with a CHO solution has been suggested to improve short (<1 h)
      endurance performance through central effect. We examined the effects of mouth
      rinsing with a CHO solution on running time to exhaustion on a treadmill. Six
      well-trained subjects ran to exhaustion at 85% VO2max , on three separate
      occasions. Subjects received either an 8% CHO solution or a placebo (PLA) every
      15 min to mouth rinse (MR) or a 6% CHO solution to ingest (ING). Treatments were
      assigned in a randomized, counterbalanced fashion, with the mouth-rinsing
      treatments double-blinded. Blood samples were taken to assess glucose (Glu) and
      lactate (Lac), as well as the perceived exertion (RPE). Gas exchange and heart
      rate (HR) were collected during all trials. Subjects ran longer (P = 0.038) in
      both the MR (2583 +/- 686 s) and ING (2625 +/- 804 s) trials, compared to PLA
      (1935 +/- 809 s), covering a greater distance (MR 9685 +/- 3511.62 m; ING 9855 +/
      4118.62; PLA 7295 +/- 3727 m). RER was significantly higher in both ING and MR
      versus PLA. No difference among trials was observed for other metabolic or
      cardiovascular variables (VO2 , Lac, Glu, HR), nor for RPE. Endurance capacity,
      based on time to exhaustion on a treadmill, was improved when either mouth
      rinsing or ingesting a CHO solution, compared to PLA.

PMID- 26302886
TI  - The shrimp mitochondrial FoF1-ATPase inhibitory factor 1 (IF1).
AB  - The whiteleg shrimp species Litopenaeus vannamei is exposed to cyclic changes of
      the dissolved oxygen concentration of seawater and must neutralize the adverse
      effects of hypoxia by using ATP as energy source. In crustaceans, the
      mitochondrial FOF1-ATP synthase is pivotal to the homeostasis of ATP and function
      prevalently as a FOF1-ATPase. Hitherto, it is unknown whether these marine
      invertebrates are equipped with molecules able to control the FOF1-ATPase
      inhibiting the ATP consumption. In this study, we report two variants of the
      mitochondrial FOF1-ATPase Inhibitory Factor 1 (IF1) ubiquitously expressed across
      tissues of the Litopenaeus vannamei transcriptome: the IF1_Lv1 and the IF1_Lv2.
      The IF1_Lv1, with a full-length sequence of 550 bp, encodes a 104 aa long protein
      and its mRNA amounts are significantly affected by hypoxia and re-oxygenation.
      The IF1_Lv2, with a sequence of 654 bp, encodes instead for a protein of 85 aa.
      Both proteins share a 69 % homology and contain a conserved minimal inhibitory
      sequence (IATP domain) along with a G-rich region on their N-terminus typical of
      the invertebrate. In light of this characterization IF1 is here discussed as an
      adaptive mechanism evolved by this marine species to inhibit the FOF1-ATPase
      activity and avoid ATP dissipation to thrive in spite of the changes in oxygen
      tension.

PMID- 26302887
TI  - Cortisol, HDL-c, VLDL-c, and APOE Polymorphisms as Laboratorial Parameters
      Associated to Cognitive Impairment No Dementia (CIND) and Dementia.
AB  - BACKGROUND: Population aging is a global phenomenon whose main consequence is the
      increase of chronic degenerative diseases, including dementia. The aim of this
      case-control study was to evaluate the laboratorial parameters lipid profile,
      cortisol, and apolipoprotein E (APOE) gene genotype, comparing cognitively
      healthy controls and subjects with cognitive impairment no dementia (CIND) and
      dementia in a group of elderly people. METHODS: Three hundred and nine
      individuals enrolled in the Pieta Study (Brazil) were divided into three groups:
      control (n = 158), CIND (n = 92), and dementia (n = 59). Participants were
      interviewed, went through examination, and had blood samples taken. RESULTS: Age
      and APOE showed significant differences among the groups, while sex and lipid
      profile did not. According to multivariate regression logistic analyses, higher
      cortisol levels, lower high-density lipoprotein (HDL-c) and very low-density
      lipoprotein (VLDL-c), presence of epsilon4 allele of APOE, and aging were
      associated with CIND and dementia. CONCLUSION: These laboratorial parameters are
      risk factors associated to CIND and dementia in the elderly people and should be
      investigated in order to develop strategies to prevent or delay the onset of
      dementia in the oldest-old populations.

PMID- 26302889
TI  - Synthesis of Silicate Zeolite Analogues Using Organic Sulfonium Compounds as
      Structure-Directing Agents.
AB  - A microporous crystalline silica zeolite of the MEL structure type and three
      other zeolite analogues composed of germanosilicate frameworks were synthesized
      using tributylsulfonium, triphenylsulfonium, or tri(para-tolyl)sulfonium as the
      structure-directing agent. The germanosilicates thus obtained had ISV, ITT, or a
      new zeolite structure depending on the synthesis conditions. The structure of the
      new germanosilicate was solved using X-ray powder diffraction data with the aid
      of a charge-flipping method. The solution indicated a crystal structure belonging
      to the P63/mmc space group with cell parameters of a=16.2003 A and c=21.8579 A.
      After calcination, the new germanosilicate material exhibited two types of
      accessible micropores with diameters of 0.61 and 0.78 nm. 

PMID- 26302888
TI  - An Evaluation of Patient Comfort During Acute Psychiatric Hospitalization.
AB  - PURPOSE: To assess the difference in the level of comfort between psychiatric
      inpatients who received a warmed blanket and psychiatric inpatients who did not
      receive a warmed blanket. DESIGN AND METHODS: A descriptive pilot study from a
      convenience sample of 37 psychiatric patients aged 18-59. Subject's level of
      comfort was measured with Kolcaba's verbal rating scale (VRS). FINDINGS:
      Independent t-tests showed that the VRS mean score was lower in the control group
      (6.81) than the experimental group (7.29). PRACTICE IMPLICATIONS: Comfort is
      central to nursing and there has been little research regarding the effects of
      warm topical applications in the psychiatric hospital setting. Warmed blankets
      are not routinely offered to patients in the psychiatric setting. The use of
      warmed blankets may increase patient comfort.

PMID- 26302890
TI  - [Organisational challenges of community information offices for the elderly in
      Switzerland : A qualitative study with ethical reflections].
AB  - BACKGROUND: Current Swiss politics concerning age and ageing are orientated
      towards the principle "out-patient before in-patient". As part of new
      regulations, in 2011 all communities were required to set up information offices
      to answer questions about out-patient and in-patient care. OBJECTIVES: The aim of
      this qualitative study was to analyse in which form and under which conditions
      such information offices are run. METHODS: A qualitative study was conducted
      which consisted of semistructured interviews with managers of information
      offices. They were analysed using qualitative content analysis. RESULTS: The
      analysis shows that on the one hand the information offices have the potential to
      serve an important role in the communities and that they have a highly complex,
      demanding and responsible function. On the other hand the results illustrate that
      in organisational respects the situation is highly heterogeneous and unregulated.
      CONCLUSION: For the running of the information offices, there is need for action
      such as the definition of general framework, quality standards, qualifications
      and values profiles, objectives, mission, responsibility and legitimation,
      instruments for networking and cooperations.

PMID- 26302892
TI  - More about cellular signaling by antiphospholipid antibodies.

PMID- 26302893
TI  - Pristimerin Inhibits Prostate Cancer Bone Metastasis by Targeting PC-3 Stem Cell
      Characteristics and VEGF-Induced Vasculogenesis of BM-EPCs.
AB  - BACKGROUND/AIMS: Prostate cancer (PCa) is one of the most common malignant
      cancers and a major leading cause of cancer deaths in men. Cancer stem-like cells
      are shown to be highly tumorigenic, pro-angiogenic and can significantly
      contribute to tumor new vessel formation and bone marrow derived-EPCs (BM-EPCs)
      are shown to recruit to the angiogenic switch in tumor growth and metastatic
      progression, suggesting the importance of targeting cancer stem cells (CSCs) and
      EPCs for novel tumor therapies. Pristimerin, an active component isolated from
      Celastraceae and Hippocrateaceae, has shown anti-tumor effects in some cell lines
      in previous studies. However, the effect and mechanism of Pristimerin on CSCs and
      EPCs in PCa bone metastasis are not well studied. METHODS: The effect of
      Pristimerin on PC-3 stem cell characteristics and metastasis were detected by
      spheroid formation, CD133 and CD44 protein expression, matrix-gel invasive assay
      and colony-formation assay in vitro, VEGF and pro-inflammatory cytokines
      expression by ELISA assay, and tumor tumorigenicity by X-ray and MR in NOD-SCID
      mice model in vivo. In addition, we also detected the effect of Pristimerin on
      VEGF-induced vasculogenesis and protein expression of BM-EPCs. RESULTS:
      Pristimerin could significantly inhibit spheroid formation and protein expression
      of CD133 and CD44, reduce VEGF and pro-inflammation cytokines expression of PC-3
      cell, and prevent the xenografted PC-3 tumor growth in the bone of nude mice. The
      present data also showed that Pristimerin significantly inhibited VEGF-induced
      vasculogenesis of BM-EPCs by suppressing the EPCs functions including
      proliferation, adhesion, migration, tube formation and inactivation the
      phosphorylation of VEGFR-2, Akt and eNOS. CONCLUSION: These data provide evidence
      that Pristimerin has strong potential for development as a novel agent against
      prostate bone metastasis by suppressing PC-3 stem cell characteristics and VEGF
      induced vasculogenesis of BM-EPCs.

PMID- 26302895
TI  - Myeloma Propagating Cells, Drug Resistance and Relapse.
AB  - Multiple myeloma (MM) is an incurable tumor of the plasma cells, the terminally
      differentiated immunoglobulin secreting B lineage cells. The genetic make-up of
      MM has been extensively characterized but its impact on the biology of the
      disease is incomplete without more precise knowledge of the identity and
      functional role of cells with multiple myeloma propagating activity (MMPA). We
      review here recent data that link MMPA with myeloma clonotypic populations
      organized in a cellular hierarchy that mirrors normal B cell development and also
      with drug resistance and disease relapse. We further propose a conceptual
      framework which, with optimal use of recent technological advances in genomics
      and phenomics, could allow dissection of the cellular and molecular properties of
      cells with MMPA, drug resistance and in vivo relapse in an integrated and patient
      specific manner. There is real hope that these approaches will significantly
      contribute to further improvements in disease control, overall survival, and
      possibly cure of patients with MM.

PMID- 26302896
TI  - Secondary tumors involving the thyroid gland: A multi-institutional analysis of
      28 cases diagnosed on fine-needle aspiration.
AB  - BACKGROUND: Fine-needle aspiration (FNA) is routinely used to evaluate primary
      thyroid lesions (PTLs), however, its role in diagnosing secondary thyroid
      neoplasms (STNs) has not been extensively studied. The goal was to examine the
      clinical and cytopathologic features of STNs diagnosed on FNA. METHODS: The
      clinico-pathologic features of 28 STNs were analyzed. All PTLs, lymphomas, and
      locally invasive tumors were excluded. RESULTS: There were 28 STNs (0.18%
      incidence) out of 15,800 thyroid FNAs (12 males, 16 females, 32 - 85 years), all
      occurring metachronously (3 weeks-20 years, average 78.3 months) comprising 24
      (85.7%) metastatic carcinomas (14 [50%] renal; 4 [14.3%] head and neck squamous
      cell carcinomas, 3 [10.7%] breast, and 1 [3.6%] colorectal, uterine serous
      carcinoma, and lung adenosquamous carcinoma, respectively), 3 sarcomas (10.7%)
      and 1 melanoma (3.6%). CONCLUSIONS: STNs are rare and diverse tumors which may
      occur decades after primary malignancy. Renal carcinomas are the most common.
      Prior history of malignancy, high index of suspicion, and attention to key
      distinguishing cytologic clues are critical for accurate diagnosis.

PMID- 26302897
TI  - Dynamic modulation of electronic properties of graphene by localized carbon
      doping using focused electron beam induced deposition.
AB  - We report on the first demonstration of controllable carbon doping of graphene to
      engineer local electronic properties of a graphene conduction channel using
      focused electron beam induced deposition (FEBID). Electrical measurements
      indicate that an "n-p-n" junction on graphene conduction channel is formed by
      partial carbon deposition near the source and drain metal contacts by low energy
      (<50 eV) secondary electrons due to inelastic collisions of long range
      backscattered primary electrons generated from a low dose of high energy (25 keV)
      electron beam (1 * 10(18) e(-) per cm(2)). Detailed AFM imaging provides direct
      evidence of the new mechanism responsible for dynamic evolution of the locally
      varying graphene doping. The FEBID carbon atoms, which are physisorbed and weakly
      bound to graphene, diffuse towards the middle of graphene conduction channel due
      to their surface chemical potential gradient, resulting in negative shift of
      Dirac voltage. Increasing a primary electron dose to 1 * 10(19) e(-) per cm(2)
      results in a significant increase of carbon deposition, such that it covers the
      entire graphene conduction channel at high surface density, leading to n-doping
      of graphene channel. Collectively, these findings establish a unique capability
      of FEBID technique to dynamically modulate the doping state of graphene, thus
      enabling a new route to resist-free, "direct-write" functional patterning of
      graphene-based electronic devices with potential for on-demand re
      configurability. 

PMID- 26302898
TI  - Synthesis and Antihypertensive Action of New Imidazo[1,2-a]pyridine Derivatives ,
      non Peptidic Angiotensin II Receptor Antagonists.
AB  - The synthesis and antihypertensive activity of a group of imidazo[1,2-a]pyridine
      is described. New synthesized compound have been tested both in vivo and in vitro
      as antagonists on Angiotensin AT1 receptor, and compared to Losartan, used as
      reference drug. Binding assay an Angiotensin AT1 receptor were carried on as
      well. Compounds 6b and 6g showed a potent antihypertensive activity and an high
      affinity on AT1 receptor. 

PMID- 26302899
TI  - Integrated Transcriptomics Establish Macrophage Polarization Signatures and have
      Potential Applications for Clinical Health and Disease.
AB  - Growing evidence defines macrophages (Mphi) as plastic cells with wide-ranging
      states of activation and expression of different markers that are time and
      location dependent. Distinct from the simple M1/M2 dichotomy initially proposed,
      extensive diversity of macrophage phenotypes have been extensively demonstrated
      as characteristic features of monocyte-macrophage differentiation, highlighting
      the difficulty of defining complex profiles by a limited number of genes. Since
      the description of macrophage activation is currently contentious and confusing,
      the generation of a simple and reliable framework to categorize major Mphi
      phenotypes in the context of complex clinical conditions would be extremely
      relevant to unravel different roles played by these cells in pathophysiological
      scenarios. In the current study, we integrated transcriptome data using
      bioinformatics tools to generate two macrophage molecular signatures. We
      validated our signatures in in vitro experiments and in clinical samples. More
      importantly, we were able to attribute prognostic and predictive values to
      components of our signatures. Our study provides a framework to guide the
      interrogation of macrophage phenotypes in the context of health and disease. The
      approach described here could be used to propose new biomarkers for diagnosis in
      diverse clinical settings including dengue infections, asthma and sepsis
      resolution. 

PMID- 26302900
TI  - Indoor rock climbing (bouldering) as a new treatment for depression: study design
      of a waitlist-controlled randomized group pilot study and the first results.
AB  - BACKGROUND: Depression is one of the most common diseases in industrialised
      nations. Physical activity is regarded as an important part of therapeutic
      intervention. Rock climbing or bouldering (rock climbing to moderate heights
      without rope) comprises many aspects that are considered useful, but until now,
      there has been hardly any research on the effects of a bouldering group
      intervention on people with depression. The purpose of this controlled pilot
      study was twofold: first, to develop a manual for an eight-week interventional
      program that integrates psychotherapeutic interventions in a bouldering group
      setting and second, to assess the effects of a bouldering intervention on people
      with depression. METHODS: The intervention took place once a week for three hours
      across a period of eight weeks. Participants were randomly assigned to the two
      groups (intervention vs. waitlist). The intervention group began the bouldering
      therapy immediately after a baseline measurement was taken; the waitlist
      participants began after an eight-week period of treatment as usual. On four
      measurement dates at eight-week intervals, participants completed the Beck
      Depression Inventory II (BDI-II), the symptom checklist-90-R (SCL-90), the
      questionnaire on resources and self-management skills (FERUS), and the attention
      test d2-R. A total of 47 participants completed the study, and the data were
      analysed with descriptive statistics. Cohen's d was calculated as a measure of
      the effect size. For the primary hypothesis, a regression analysis and the Number
      Needed to Treat (NNT) (improvement of at least 6 points on the BDI-II) were
      calculated. RESULTS: After eight weeks of intervention, results indicated
      positive effects on the measures of depression (primary hypothesis: BDI-II:
      Cohen's d = 0.77), this was supported by the regression analysis with "group" as
      the only significant predictor of a change in depression (p = .007). The NNT was
      four. CONCLUSIONS: These findings provide the first evidence that therapeutic
      bouldering may offer an effective treatment for depression. Further research is
      required. TRIAL REGISTRATION: Current controlled trials, ISRCTN17623318 ,
      registered on July 15(th) 2015.

PMID- 26302901
TI  - Circumstances leading to intimate partner violence against women married as
      children: a qualitative study in Urban Slums of Lahore, Pakistan.
AB  - BACKGROUND: Child marriage (<18 years) is prevalent in Pakistan which is
      associated with negative health outcomes including intimate partner violence
      (IPV). Our aim is to describe the types and circumstances of IPV against women
      who were married as children in urban slums of Lahore, Pakistan. METHODS: Women
      of reproductive age (15-49 years) who were married prior to 18 years, for at
      least 5 years were recruited from most populous slum areas of Lahore, Pakistan.
      Themes for the interview guide were developed using published literature and
      everyday observations of the researchers. Interviews were conducted by trained
      interviewers in Urdu language and were translated into English. The interviews
      were tape-recorded, transcribed, analyzed and categorized into themes. RESULTS:
      All 19 participants were married between 11 and 17 years. Most respondents were
      uneducated, poor and were working as housemaids. Majority of participants
      experienced verbal abuse, and threatened, attempted and completed physical
      violence by their husbands. A sizeable number of women reported unwanted sexual
      encounters by their husbands. Family affairs particularly issues with in-laws,
      poor house management, lack of proper care of children, bringing insufficient
      dowry, financial problems, an act against the will of husband, and inability to
      give birth to a male child were some of the reasons narrated by the participants
      which led to IPV against women. CONCLUSIONS: Women married as children are
      vulnerable to IPV. Concerted efforts are needed from all sectors of society
      including academia, public health experts, policy makers and civil society to end
      the child marriage practice in Pakistan.

PMID- 26302902
TI  - Ascaris and hookworm transmission in preschool children from rural Panama: role
      of yard environment, soil eggs/larvae and hygiene and play behaviours.
AB  - This study explored whether the yard environment and child hygiene and play
      behaviours were associated with presence and intensity of Ascaris and hookworm in
      preschool children and with eggs and larvae in soil. Data were collected using
      questionnaires, a visual survey of the yard, soil samples and fecal samples
      collected at baseline and following re-infection. The presence of eggs/larvae in
      soil was associated negatively with water storage (eggs) but positively with dogs
      (eggs) and distance from home to latrine (larvae). Baseline and re-infection
      prevalences were: hookworm (28.0%, 3.4%); Ascaris (16.9%, 9.5%); Trichuris (0.9%,
      0.7%). Zero-inflated negative binomial regression models revealed a higher
      baseline hookworm infection if yards had eggs or larvae, more vegetation or
      garbage, and if the child played with soil. Baseline Ascaris was associated with
      dirt floor, dogs, exposed soil in yard, open defecation and with less time
      playing outdoors, whereas Ascaris re-infection was associated with water storage,
      vegetation cover and garbage near the home and not playing with animals. Our
      results show complex interactions between infection, the yard environment and
      child behaviours, and indicate that transmission would be reduced if latrines
      were closer to the home, and if open defecation and water spillage were reduced.

PMID- 26302903
TI  - Delivery of siRNA via cationic Sterosomes to enhance osteogenic differentiation
      of mesenchymal stem cells.
AB  - Noggin is a specific antagonist of bone morphogenetic proteins (BMPs) that can
      prevent the interaction of BMPs with their receptors. RNA interfering molecules
      have been used to downregulate noggin expression and thereby stimulate BMP
      signaling and osteogenesis. Cationic liposomes are considered one of the most
      efficient non-viral systems for gene delivery. In the past decade, non
      phospholipid liposomes (Sterosomes) formulated with single-chain amphiphiles and
      high content of sterols have been developed. In particular, Sterosomes composed
      of stearylamine (SA) and cholesterol (Chol) display distinct properties compared
      with traditional phospholipid liposomes, including increased positive surface
      charges and enhanced particle stability. Herein, we report SA/Chol Sterosome and
      small interfering RNA (siRNA) complexes that significantly enhanced cellular
      uptake and gene knockdown efficiencies in adipose derived mesenchymal stem cells
      with minimal cytotoxicity compared with commercially available lipofectamine
      2000. Furthermore, we confirmed osteogenic efficacy of these Sterosomes loaded
      with noggin siRNA in in vitro two- and three-dimensional settings as well as in a
      mouse calvarial defect model. The delivery of siRNA via novel SA/Chol Sterosomes
      presents a powerful method for efficient gene knockdown. These distinct
      nanoparticles may present a promising alternative approach for gene delivery. 

PMID- 26302906
TI  - Apple juice attenuates genotoxicity and oxidative stress induced by cadmium
      exposure in multiple organs of rats.
AB  - The aim of this study was to evaluate the health benefits associated with apple
      consumption following cadmium exposure. A total of 15 Wistar rats were
      distributed into three groups (n=5), as follows: control group (non-treated
      group, CTRL); cadmium group (Cd) and apple juice group (Cd+AJ). The results
      showed a decrease in the frequency micronucleated cells in bone marrow and
      hepatocytes in the group exposed to cadmium and treated with apple juice. Apple
      juice was also able to reduce the 8OHdG levels and to decrease genetic damage in
      liver and peripheral blood cells. Catalase (CAT) was decreased following apple
      juice intake. Taken together, our results demonstrate that apple juice seems to
      be able to prevent genotoxicity and oxidative stress induced by cadmium exposure
      in multiple organs of Wistar rats. 

PMID- 26302904
TI  - S-Nitrosated human serum albumin dimer as novel nano-EPR enhancer applied to
      macromolecular anti-tumor drugs such as micelles and liposomes.
AB  - The enhanced permeability and retention (EPR) effect is a unique phenomenon of
      solid tumors, and it can serve as a basis for the development of macromolecular
      anticancer therapy. We have previously found that recombinant human serum albumin
      dimer, and especially its S-nitrosated form (SNO-HSA-Dimer), is an enhancer of
      the EPR effect. In this study, we investigated the influence of SNO-HSA-Dimer on
      the anti-tumor effect of two types of macromolecular anti-tumor drugs, namely N
      (2-hydroxypropyl)methacrylamide polymer conjugated with zinc protoporphyrin,
      which forms micelles and can be used for fluorescence studies. The other was
      PEGylated liposomal doxorubicin (Doxil), a typical example of a stealth liposome
      approved for medical usage. In mice having C26 tumors with highly permeable
      vasculature, SNO-HSA-Dimer increases tumor accumulation of the drugs by a factor
      3-4 and thereby their anti-tumor effects. Experiments with Evans blue revealed
      increased EPR effect in all parts of the tumor. Furthermore, SNO-HSA-Dimer
      improves the anti-metastatic effects of Doxil and reduces its minor uptake in non
      tumorous organs such as liver and kidney. Tumor accumulation of Doxil in B16
      tumors, which are characterized by a low permeable vasculature, increased even
      more (6-fold) in the presence of SNO-HSA-Dimer, and the improved accumulation
      lead to decreased tumor volume and increased survival of the animals. The
      administration of SNO-HSA-Dimer itself is safe, because it has no effect on blood
      pressure, heart rate or on several biochemical parameters. The present findings
      indicate that SNO-HSA-Dimer is promising for enhancing the EPR effect and
      consequently the specific, therapeutic effects of macromolecular anticancer
      drugs. 

PMID- 26302905
TI  - Analysis of potassium iodate reduction in tissue homogenates using high
      performance liquid chromatography-inductively coupled plasma-mass spectrometry.
AB  - Potassium iodate (KIO3) and potassium iodide (KI) are the major salt iodization
      agents used worldwide. Unlike iodide (I(-)), iodate (IO3(-)) should be reduced to
      I(-) before it can be effectively used by the thyroid. In this study, we
      developed a new method for analyzing IO3(-) and I(-) in tissue homogenates using
      high performance liquid chromatography coupled to inductively coupled plasma mass
      spectrometry (HPLC-ICP-MS). We further applied the method to demonstrate the KIO3
      reduction process by tissues in vitro. The effects of KIO3 on the total
      antioxidative activity (TAA) and reduced nicotinamide adenine dinucleotide
      phosphate (NADPH) were also investigated here. Finally, we found that IO3(-) can
      be reduced to I(-) by tissue homogenates and IO3(-) irreversibly decreases the
      antioxidant capability of tissues. Our studies suggest that KIO3 might have a big
      effect on the redox balance of tissue and would further result in oxidative
      stress of organisms. 

PMID- 26302907
TI  - In vivo determination of aluminum, cobalt, chromium, copper, nickel, titanium and
      vanadium in oral mucosa cells from orthodontic patients with mini-implants by
      Inductively coupled plasma-mass spectrometry (ICP-MS).
AB  - Miniscrews are used as orthodontic anchorage devices in the dentistry clinical
      practice but the in vivo metallic release from these structures has been not
      previously investigated. The aim of this study was to determine the content of
      Al, Co, Cr, Cu, Ni, Ti and V in oral mucosa cells of control subjects, patients
      under orthodontic treatment and with both, orthodontic treatment and miniscrew,
      in order to know the contribution of these mini-implants to the total metallic
      content. ICP-MS measurements revealed the following ascending order:
      Cr<Ni<Ti<Cu<Al, and Co and V were practically undetected. Significant differences
      in comparison to the control group were found for Cu in the orthodontic group,
      and for Ni in both, orthodontic and orthodontic+miniscrew groups. Potential
      correlations among metallic elements and with some clinical factors were also
      explored. These findings suggest that miniscrews do not increase significantly
      the metal release. 

PMID- 26302908
TI  - Interaction between vitamin B6 and source of selenium on the response of the
      selenium-dependent glutathione peroxidase system to oxidative stress induced by
      oestrus in pubertal pig.
AB  - This study aimed to assess the interaction between vitamin B6 and selenium (Se)
      for the flow of Se towards the Se-dependent glutathione peroxidase (GPX) system
      in response to oxidative stress naturally induced by oestrus in a pubertal pig
      model. At first oestrus, forty-five gilts were randomly assigned to the
      experimental diets (n=9/group): basal diet (CONT); CONT+0.3mg/kg of Na-selenite
      (MSeB60); MSeB60+10mg/kg of HCl-B6 (MSeB610); CONT+0.3mg/kg of Se-enriched yeast
      (OSeB60); and OSeB60+10mg/kg of HCl-B6 (OSeB610). Blood samples were collected at
      each oestrus (long-term profiles), and daily from day -4 to +3 (slaughter) of the
      fourth oestrus (peri-oestrus profiles) after which liver, kidneys, and ovaries
      were collected. For long-term profiles, CONT had lower blood Se than Se
      supplemented gilts (p<0.01) and OSe was higher than MSe (p<0.01). Lower
      erythrocyte pyridoxal-5-phosphate was found in B60 than B610 (p<0.01). No
      treatment effect was observed on GPX activity. For peri-oestrus profiles,
      treatment effects were similar to long-term profiles. Treatment effects on liver
      Se were similar to those for long-term blood Se profiles and OSe had higher renal
      Se concentrations than MSe gilts (p<0.01). Gene expressions of GPX1, GPX3, GPX4,
      and selenocysteine lyase in liver and kidney were greatest in OSeB610 gilts
      (p<0.05). These results suggest that dietary B6 modulate the metabolic pathway of
      OSe towards the GPX system during the peri-oestrus period in pubertal pigs. 

PMID- 26302909
TI  - Biomedical potential of actinobacterially synthesized selenium nanoparticles with
      special reference to anti-biofilm, anti-oxidant, wound healing, cytotoxic and
      anti-viral activities.
AB  - Currently, there is an ever-increasing need to develop environmentally benign
      processes in place of synthetic protocols. As a result, researchers in the field
      of nanoparticle synthesis are focusing their attention on microbes from rare
      biological ecosystems. One potential actinobacterium, Streptomyces
      minutiscleroticus M10A62 isolated from a magnesite mine had the ability to
      synthesize selenium nanoparticles (SeNPs), extracellularly. Actinobacteria
      mediated SeNP synthesis were characterized by UV-visible, Fourier transform
      infrared (FT-IR), X-ray diffraction (XRD), energy dispersive X-ray spectroscopy
      (EDX) and high resolution transmission electron microscopy (HR-TEM) analysis. The
      UV-spectral analysis of SeNPs indicated the maximum absorption at 510nm, FT-IR
      spectral analysis confirms the presence of capping protein, peptide, amine and
      amide groups. The selenium signals confirm the presence of SeNPs. All the
      diffraction peaks in the XRD pattern and HR-TEM confirm the size of SeNPs in the
      range of 10-250nm. Further, the anti-biofilm and antioxidant activity of the
      SeNPs increased proportionally with rise in concentration, and the test strains
      reduced to 75% at concentration of 3.2MUg. Selenium showed significant anti
      proliferative activity against HeLa and HepG2 cell lines. The wound healing
      activity of SeNPs reveals that 5% selenium oinment heals the excision wound of
      Wistar rats up to 85% within 18 days compared to the standard ointment. The
      biosynthesized SeNPs exhibited good antiviral activity against Dengue virus. The
      present study concludes that extremophilic actinobacterial strain was a novel
      source for SeNPs with versatile biomedical applications and larger studies are
      needed to quantify these observed effects of SeNPs. 

PMID- 26302910
TI  - Quantification of titanium from TiO2 particles in biological tissue.
AB  - This study presents the development of a strategy for the quantification of
      titanium from titanium dioxide polydisperse particles (TiO2) in dry biological
      tissue. Calf liver was chosen as laboratory testing material. The challenge was
      to (i) obtain a complete mineralization of the solid material (biological tissue
      and TiO2) and (ii) ensure the accuracy of the determined concentrations with a
      sufficient sensitivity. Mineralization was performed using a mixture of
      concentrated nitric and hydrofluoric acids. Atomic mass spectrometry associated
      with light-scattering technique was used to control the physical state (dissolved
      and particle forms) of titanium and reliably estimate the total titanium
      concentration in calf liver. The monitoring of (46)Ti and (49)Ti, operating in
      helium collision/reaction cell mode, and using external calibration with internal
      standard addition, allowed the quantification of Ti while removing isobaric
      interferences. The limit of detection and quantification were 0.7 and 2.3MUg
      (Ti)g(-1) (tissue) respectively. The mean analytical recovery over the whole
      procedure was (103+/-6)% in a range of concentrations from LOD to 200MUg(Ti)g(-1)
      (tissue). 

PMID- 26302911
TI  - Transcription analysis of genes involved in lipid metabolism reveals the role of
      chromium in reducing body fat in animal models.
AB  - Chromium was proposed to be an essential trace element over 50 years ago and has
      been accepted as an essential element for over 30 years. The recent studies
      indicated that the addition of supra nutritional amounts of chromium to the diet
      can only be considered as having pharmacological effects. However, the precise
      mechanism through which chromium acts on lipid, carbohydrate, protein and nucleic
      acid metabolism are relatively poor studied. To uncover, at least partially, the
      role of chromium in lipid metabolism, in this study, we evaluated the expression
      status of eight important genes, involved in fat biosynthesis and lipid
      metabolism, in four different tissue types (liver, subcutaneous fat, visceral
      fat, and longissimus muscle) in domestic goat kids feeding on three different
      chromium levels. The quantitative real-time PCR (RT-PCR) was established for
      expression analyses with HSP90 gene was used as reference gene. The results
      showed that supplementation of goats with 1.5mg/day chromium significantly
      decreases the expression of the ACC1, DGAT1, FABP4, FAS, HSL, LEP genes, but does
      not affect the expression of the LPL and SCD1 genes in all studied tissues. This
      study highlights, for the first time, the role of supra nutritional levels of
      chromium in lipid biosynthesis and metabolism. These findings are of especial
      importance for improving meat quality in domestic animals. 

PMID- 26302912
TI  - Influence of diphenyl diselenide on chlorpyrifos-induced toxicity in Drosophila
      melanogaster.
AB  - Exposure to chlorpyrifos (CPF) poses several harmful effects to human and animal
      health. The present study investigated the influence of diphenyl diselenide
      (DPDS) on CPF-induced toxicity in Drosophila melanogaster. Firstly, the time
      course lethality response of virgin flies (2- to 3-day-old) to CPF (0.075
      0.6MUg/g) and DPDP (5-40MUmol/kg) in the diet for 28 consecutive days were
      investigated. Subsequently, the protective effect of DPDS (10, 20 and 40MUmol/kg)
      on CPF (0.15MUg/g)-induced mortality, locomotor deficits, neurotoxicity and
      oxidative stress was assessed in a co-exposure paradigm for 7 days. Results
      showed that CPF exposure significantly decreased the percent live flies in a time
      and concentration-dependent manner, whereas the percent live flies with DPDS
      treatment was not statistically different from control following 28 days of
      treatment. In the co-exposure study, CPF significantly increased flies mortality
      while the survivors exhibited significant locomotor deficits with decreased
      acetylcholinesterase (AChE) activity. Dietary supplementation with DPDS was
      associated with marked decrease in mortality, improvement in locomotor activity
      and restoration of AChE activity in CPF-exposed flies. Moreover, CPF exposure
      significantly decreased catalase and glutathione-S-transferase activities, total
      thiol level with concomitant significant elevation in the levels of reactive
      oxygen species and thiobarbituric acid reactive substances in the head and body
      regions of the treated flies. Dietary supplementation with DPDS significantly
      improved the antioxidant status and prevented CPF-induced oxidative stress, thus
      demonstrating the protective effect of DPDS in CPF-treated flies. 

PMID- 26302913
TI  - Association between blood cadmium level and bone mineral density reduction
      modified by renal function in young and middle-aged men.
AB  - The association between cadmium exposure and bone mineral density (BMD) has not
      been well studied in young and middle-aged men. This study examined the
      relationship between the level of blood Cd (BCd) and BMD in a young to middle
      aged representative male population while considering renal function. Using data
      from the 4th Korea National Health and Nutrition Examination Survey, 2008-2009,
      1275 adult men aged 20-64 years were analyzed. BCd was measured by atomic
      absorption spectrophotometry and renal function was assessed by the estimated
      glomerular filtration rate (eGFR) with CKD-EPI formula. The risk of lower bone
      density was increased according to the increase in BCd levels after adjusting for
      eGFR and covariates, in which a significant interaction between BCd and eGFR
      existed. Significant negative associations between BCd and BMD were found: beta
      (p-value) were -0.03 (0.02), -0.04 (0.004) and -0.03 (0.04) in total femur,
      lumbar spine and femoral neck, respectively, which were limited to the people
      with eGFR<=lower 25%. Although, a causal relationship could not be determined
      because of a cross-sectional design in the present study, the results suggest low
      level Cd toxicity to bone via low eGFR and that measures to reduce environmental
      Cd exposure may be helpful to prevent bone loss in men. 

PMID- 26302914
TI  - Beneficial effects of oral chromium picolinate supplementation on glycemic
      control in patients with type 2 diabetes: A randomized clinical study.
AB  - BACKGROUND: Chromium is an essential mineral that contributes to normal glucose
      function and lipid metabolism. This study evaluated the effect of chromium
      picolinate (CrPic) supplementation in patients with type 2 diabetes mellitus
      (T2DM). METHODS: A four month controlled, single blind, randomized trial was
      performed with 71 patients with poorly controlled (hemoglobin A1c [HbA1c]>7%)
      T2DM divided into 2 groups: Control (n=39, using placebo), and supplemented
      (n=32, using 600MUg/day CrPic). All patients received nutritional guidance
      according to the American Diabetes Association (ADA), and kept using prescribed
      medications. Fasting and postprandial glucose, HbA1c, total cholesterol, high
      density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol,
      triglycerides and serum ferritin were evaluated. RESULTS: CrPic supplementation
      significantly reduced the fasting glucose concentration (-31.0mg/dL supplemented
      group; -14.0mg/dL control group; p<0.05, post- vs. pre-treatment, in each group)
      and postprandial glucose concentration (-37.0mg/dL in the supplemented group; 
      11.5 mg/dL in the control group; p<0.05). HbA1c values were also significantly
      reduced in both groups (p<0.001, comparing post- vs. pre-treatment groups). Post
      treatment HbA1c values in supplemented patients were significantly lower than
      those of control patients. HbA1c lowering in the supplemented group (-1.90), and
      in the control group (-1.00), was also significant, comparing pre- and post
      treatment values, for each group (p<0.001 and p<0.05, respectively). CrPic
      increased serum chromium concentrations (p<0.001), when comparing the
      supplemented group before and after supplementation. No significant difference in
      lipid profile was observed in the supplemented group; however, total cholesterol,
      HDL-c and LDL-c were significantly lowered, comparing pre- and post-treatment
      period, in the control group (p<0.05). CONCLUSIONS: CrPic supplementation had a
      beneficial effect on glycemic control in patients with poorly controlled T2DM,
      without affecting the lipid profile. Additional studies are necessary to
      investigate the effect of long-term CrPic supplementation.

PMID- 26302915
TI  - Conflicting effects of BMI and waist circumference on iron status.
AB  - The association between obesity and iron status has a long history and is still
      receiving attention. However comparative analysis of the association between
      general obesity (BMI) and visceral obesity (waist circumference) with iron status
      has not been extensively researched. The aim of the present study is thus to
      determine if body mass index and waist circumference have the same correlation
      with iron status. One thousand one hundred and thirty people (225 men and 905
      women) aged 30 years and above participated in this study. Anthropometric
      parameters, haemoglobin, iron and total iron binding capacity concentrations were
      measured using standard methods. Percentage transferrin saturation was calculated
      and ferritin concentrations were measured using an enzyme linked immunosorbent
      assay. Obese or overweight women had significantly lower iron and transferrin
      saturation concentration when compared to non-obese women. In contrast, women
      with high waist circumference had comparable plasma iron and transferrin
      saturation to women with normal waist circumference. Partial correlation analysis
      and linear regression analysis showed that BMI is negatively and significantly
      associated with plasma iron, transferrin saturation, Hb and ferritin
      concentration, whilst waist circumference is positively but insignificantly
      associated with plasma iron, transferrin saturation, Hb and ferritin
      concentration. Binary regression analysis showed that obese or overweight people
      are more likely to have iron deficiency, whilst those with raised waist
      circumference are more likely to have iron overload. Multivariate analysis showed
      that body mass index is negatively and significantly associated with low iron
      status, while waist circumference is positively and insignificantly associated
      with iron status. This is supported by a comparison of plasma iron, transferrin
      saturation and ferritin concentrations in participants with high body mass index
      and normal waist circumference and participants with normal body mass index and
      high waist circumference to those participants having normal body mass index and
      normal waist circumference. The present study suggests that in women body mass
      index is associated with low plasma iron, transferrin saturation and ferritin
      concentrations, while waist circumference is associated with high plasma iron,
      transferrin saturation and ferritin concentrations. 

PMID- 26302916
TI  - The effect of zinc and phytoestrogen supplementation on the changes in mineral
      content of the femur of rats with chemically induced mammary carcinogenesis.
AB  - The aim of this study was to assess skeletal effects of zinc or zinc with
      phytoestrogen (resveratrol or genistein) supplementation in an animal model of
      rats with DMBA-induced mammary carcinogenesis. The changes in bone parameters
      such as the length and mass were examined, as well as the changes in
      concentrations of selected minerals: calcium, magnesium, zinc, iron and
      phosphorus. Moreover, the investigations focused on finding the differences
      between the levels of iron and zinc in other tissues: the liver, spleen and serum
      of the examined rats. Fifty-six female Sprague-Dawley rats, 40 days old, were
      divided into four groups, regardless of the diets: standard (77mg Zn kg/food),
      zinc (4.6mg/mL via gavage), zinc (4.6mg/mL) plus resveratrol (0.2mg/kgbw), and
      zinc (4.6mg/mL) plus genistein (0.2mg/kgbw) for a period from 40 days until 20
      weeks of age. The study rats were also treated with 7,12-dimethyl-1,2
      benz[a]anthracene (DMBA) to induce mammary carcinogenesis. The applied diet and
      the advanced mammary cancer did not affect macrometric parameters of the rats'
      bones, but they strongly affected their mineral content. It was found that
      mammary cancer, irrespectively of the applied diet, significantly modified the
      iron level in the femur, liver, spleen and serum of the examined rats. In
      addition, zinc supplementation significantly lowered the levels of calcium,
      magnesium and phosphorus in the femur of rats with mammary cancer as compared
      with respective levels in the control group. So, it was found that additional
      supplementation with zinc, which is generally considered to be an antioxidant,
      with the co-existing mammary carcinoma, increased the unfavorable changes as
      concerns the stability of bone tissue. The appropriate combination of zinc and
      phytoestrogens (resveratrol or genistein) could help prevent or slow bone loss
      associated with a range of skeletal disorders in breast cancer. 

PMID- 26302917
TI  - Effects of thirty elements on bone metabolism.
AB  - The human skeleton, made of 206 bones, plays vital roles including supporting the
      body, protecting organs, enabling movement, and storing minerals. Bones are made
      of organic structures, intimately connected with an inorganic matrix produced by
      bone cells. Many elements are ubiquitous in our environment, and many impact bone
      metabolism. Most elements have antagonistic actions depending on concentration.
      Indeed, some elements are essential, others are deleterious, and many can be
      both. Several pathways mediate effects of element deficiencies or excesses on
      bone metabolism. This paper aims to identify all elements that impact bone health
      and explore the mechanisms by which they act. To date, this is the first time
      that the effects of thirty minerals on bone metabolism have been summarized. 

PMID- 26302918
TI  - Relationship of lead and essential elements in whole blood from school-age
      children in Nanning, China.
AB  - OBJECTIVES: The aim of this study was to investigate blood lead level and its
      relationship to essential elements (zinc, copper, iron, calcium and magnesium) in
      school-age children from Nanning, China. METHODS: A total of 2457 children aged
      from 6 to 14 years were enrolled in Nanning, China. The levels of lead (Pb), zinc
      (Zn), copper (Cu), iron (Fe), calcium (Ca) and magnesium (Mg) were determined by
      an atomic absorption spectrometer. RESULTS: The mean blood lead level (BLL) was
      57.21+/-35.00MUg/L. 188 (7.65%) asymptomatic children had toxic lead level higher
      than 100MUg/L. The school-age boys had similar lead level among different age
      groups, while the elder girls had less BLL. The blood Zn and Fe were found to be
      increased in the boys with elevated BLL, but similar trends were not observed in
      the girls. Positive correlations between Pb and Fe or Mg (r=0.112, 0.062,
      respectively, p<0.01) and a negative correlation between Pb and Ca (r=-0.047,
      p<0.05) were further established in the studied children. CONCLUSIONS: Lead
      exposure in school-age children was still prevalent in Nanning. The boys and
      girls differed in blood levels of lead and other metallic elements. Lead exposure
      may induce metabolic disorder of other metallic elements in body.

PMID- 26302919
TI  - Trace elements profile is associated with insulin resistance syndrome and
      oxidative damage in thyroid disorders: Manganese and selenium interest in
      Algerian participants with dysthyroidism.
AB  - The relationship between dysthyroidism and antioxidant trace elements (ATE)
      status is very subtle during oxidative stress (OS). This relationship is mediated
      by thyroid hormone (TH) disorder, insulin resistance syndrome (IRS) and
      inflammation. The aim of this study was to investigate ATE such as selenium (Se),
      manganese (Mn), zinc (Zn) and copper (Cu) status on thyroid dysfunction, and
      their interaction with antioxidant enzyme activities, mainly, superoxide
      dismutase (SOD) and glutathione peroxidase (GPx), TH profile (TSH, T(3), T(4))
      and IRS clusters. The study was undertaken on 220 Algerian adults (30-50 years),
      including 157 women and 63 men who were divided to 4 groups: subclinical
      hypothyroidism (n = 50), overt hypothyroidism (n = 60), Graves's disease
      hyperthyroidism (n = 60) and euthyroid controls (n = 50). The IRS was confirmed
      according to NCEP (National Cholesterol Education Program). Insulin resistance
      was evaluated by HOMA-IR model. Trace elements were determined by the Flame
      Atomic Absorption Spectrometry (Flame-AAS) technique. The antioxidant enzymes
      activity and metabolic parameters were determined by biochemical methods. The TH
      profile and anti-Thyroperoxidase Antibodies (anti-TPO-Ab) were evaluated by
      radioimmunoassay. Results showed that the plasma manganese levels were
      significantly increased in all dysthyroidism groups (p <= 0.01). However, the
      plasma copper and zinc concentrations were maintained normal or not very
      disturbed vs control group. In contrast, the plasma selenium levels were highly
      decreased (p <= 0.001) and positively correlated with depletion of glutathione
      peroxidase activity; and associated both with anti-TPO-Ab overexpression and
      fulminant HS-CRP levels. This study confirms the oxidative stress-inflammation
      relationship in the dysthyroidism. The thyroid follicles antioxidant protection
      appears preserved in the cytosol (Cu/Zn-SOD), while it is altered in the
      mitochondria (Mn-SOD), which gives this cell organelle, a status of real target
      therapy in thyroid dysfunction. The publisher would like to apologise for any
      inconvenience caused. [corrected].

PMID- 26302920
TI  - Consensus document on the prevention of methylmercury exposure in Spain: Study
      group for the prevention of Me-Hg exposure in Spain (GEPREM-Hg).
AB  - The beneficial effects of fish consumption in both children and adults are well
      known. However, the intake of methylmercury, mainly from contaminated fish and
      shellfish, can have adverse health effects. The study group on the prevention of
      exposure to methylmercury (GEPREM-Hg), made up of representatives from different
      Spanish scientific societies, has prepared a consensus document in a question and
      answer format, containing the group's main conclusions, recommendations and
      proposals. The objective of the document is to provide broader knowledge of
      factors associated with methylmercury exposure, its possible effects on health
      amongst the Spanish population, methods of analysis, interpretation of the
      results and economic costs, and to then set recommendations for fish and
      shellfish consumption. The group sees the merit of all initiatives aimed at
      reducing or prohibiting the use of mercury as well as the need to be aware of the
      results of contaminant analyses performed on fish and shellfish marketed in
      Spain. In addition, the group believes that biomonitoring systems should be set
      up in order to follow the evolution of methylmercury exposure in children and
      adults and perform studies designed to learn more about the possible health
      effects of concentrations found in the Spanish population, taking into account
      the lifestyle, eating patterns and the Mediterranean diet. 

PMID- 26302921
TI  - Sodium selenite/selenium nanoparticles (SeNPs) protect cardiomyoblasts and
      zebrafish embryos against ethanol induced oxidative stress.
AB  - Alcoholic cardiomyopathy is the damage caused to the heart muscles due to high
      level of alcohol consumption resulting in enlargement and inflammation of the
      heart. Selenium is an important trace element that is beneficial to human health.
      Selenium protects the cells by preventing the formation of free radicals in the
      body. In the present study, protein mediated synthesis of SeNPs was investigated.
      Two different sizes of SeNPs were synthesized using BSA and keratin. The
      synthesized SeNPs were characterized by scanning electron microscopy (SEM) with
      elemental composition analysis Energy Dispersive X-ray spectroscopy(EDX) and X
      ray diffraction (XRD). This study demonstrates the in vitro and in vivo
      antioxidative effects of sodium selenite and SeNPs. Further selenium and SeNPs
      were evaluated for their ability to protect against 1% ethanol induced oxidative
      stress in H9C2 cell line. The selenium and SeNPs were found to reduce the 1%
      ethanol-induced oxidative damage through scavenging intracellular reactive oxygen
      species. The selenium and SeNPs could also prevent pericardial edema induced
      ethanol treatment and reduced apoptosis and cell death in zebrafish embryos. The
      results indicate that selenium and SeNPs could potentially be used as an additive
      in alcoholic beverage industry to control the cardiomyopathy. 

PMID- 26302922
TI  - An approach for manganese biomonitoring using a manganese carrier switch in serum
      from transferrin to citrate at slightly elevated manganese concentration.
AB  - After high-dose-short-term exposure (usually from occupational exposure) and even
      more under low-dose long term exposure (mainly environmental) manganese (Mn)
      biomonitoring is still problematic since these exposure scenarios are not
      necessarily reflected by a significant increase of total Mn in blood or serum.
      Usually, Mn concentrations of exposed and unexposed persons overlap and
      individual differentiation is often not possible. In this paper Mn speciation on
      a large sample size (n=180) was used in order to be able to differentiate between
      highly Mn-exposed or low or unexposed individuals at low total Mn concentration
      in serum (Mn(S)). The whole sample set consisted of three subsets from Munich,
      Emilia Romagna region in Italy and from Sweden. It turned out that also at low
      total Mn(S) concentrations a change in major Mn carriers in serum takes place
      from Mn-transferrin (Mn-Tf(S)) towards Mn-citrate (Mn-Cit(S)) with high
      statistical significance (p<0.000002). This carrier switch from Mn-Tf(S) to Mn
      Cit(S) was observed between Mn(S) concentrations of 1.5MUg/L to ca. 1.7MUg/L.
      Parallel to this carrier change, for sample donors from Munich where serum and
      cerebrospinal fluid were available, the concentration of Mn beyond neural
      barriers - analysed as Mn in cerebrospinal fluid (Mn(C)) - positively correlates
      to Mn-Cit(S) when Mn(S) concentration was above 1.7MUg/L. The correlation between
      Mn-Cit(S) and Mn(C) reflects the facilitated Mn transport through neural barrier
      by means of Mn-citrate. Regional differences in switch points from Mn-Tf(S) to Mn
      Cit(S) were observed for the three sample subsets. It is currently unknown
      whether these differences are due to differences in location, occupation, health
      status or other aspects. Based on our results, Mn-Cit(S) determination was
      considered as a potential means for estimating the Mn load in brain and CSF,
      i.e., it could be used as a biomarker for Mn beyond neural barrier. For a simpler
      Mn-Cit(S) determination than size exclusion chromatography inductively coupled
      plasma mass spectrometry (SEC-ICP-MS), ultrafiltration (UF) of serum samples was
      tested for suitability, the latter possibly being a preferred choice for routine
      occupational medicine laboratories. Our results revealed that UF could be an
      alternative if methodical prerequisites and limitations are carefully considered.
      These prerequisites were determined to be a thorough cleaning procedure at a
      minimum Mn(S) concentration >1.5MUg/L, as at lower concentrations a wide
      scattering of the measured concentrations in comparison to the standardized SEC
      ICP-MS results were observed. 

PMID- 26302923
TI  - Ameliorative effect of vanadyl(IV)-ascorbate complex on high-fat high-sucrose
      diet-induced hyperglycemia, insulin resistance, and oxidative stress in mice.
AB  - There is mounting evidence demonstrating causative links between hyperglycemia,
      oxidative stress, and insulin resistance, the core pathophysiological features of
      type 2 diabetes mellitus. Using a combinational approach, we synthesized a
      vanadium-antioxidant (i.e., l-ascorbic acid) complex and examined its effect on
      insulin resistance and oxidative stress. This study was designed to examine
      whether vanadyl(IV)-ascorbate complex (VOAsc) would reduce oxidative stress,
      hyperglycemia, and insulin resistance in high-fat high-sucrose diet (HFSD)
      induced type 2 diabetes in mice. Male C57BL/6J mice were fed a HFSD for 12 weeks
      to induce insulin resistance, rendering them diabetic. Diabetic mice were treated
      with rosiglitazone, sodium l-ascorbate, or VOAsc. At the end of treatment,
      fasting blood glucose, fasting serum insulin, homeostasis model assessment
      insulin resistance index, and serum adipocytokine levels were measured. Serum
      levels of nitric oxide (NO) parameters were also determined. The liver was
      isolated and used for determination of malondialdehyde, reduced glutathione, and
      catalase levels, and superoxide dismutase and glutathione peroxidase activities.
      VOAsc groups exhibited significant reductions in serum adipocytokine and NO
      levels, and oxidative stress parameters compared to the corresponding values in
      the untreated diabetic mice. The results indicated that VOAsc is non-toxic. In
      conclusion, we identified VOAsc as a potentially effective adjunct therapy for
      the management of type 2 diabetes. 

PMID- 26302924
TI  - Inflammation neither increases hepatic hepcidin nor affects intestinal (59)Fe
      absorption in two murine models of bowel inflammation, hemizygous TNF(DeltaARE/+)
      and homozygous IL-10(-/-) mice.
AB  - Hepcidin-synthesis was reported to be stimulated by inflammation. In contrast,
      hepcidin synthesis was inhibited by TNFalpha and serum hepcidin was low. To
      elucidate these contradictions, we compare data on hepcidin expression, on iron
      absorption and homoeostasis and markers of inflammation between two murine models
      of intestinal inflammation and corresponding wild-types as determined by standard
      methods. In TNF(DeltaARE/+) and IL-10(-/-)-mice hepatic hepcidin expression and
      protein content was significantly lower than in corresponding wild-types.
      However, (59)Fe whole-body retention showed no difference between knock-outs and
      corresponding wild-types 7d after gavage, in neither strain. Compared to wild
      types, body weight, hepatic non-haem iron content, hemoglobin and hematocrit were
      significantly decreased in TNF(DeltaARE/+) mice, while erythropoiesis increased.
      These differences were not seen in IL-10(-/-) mice. Duodenal IL-6 and TNFalpha
      content increased significantly in TNF(DeltaARE/+) mice, while ferritin-H
      decreased along with hepatic hepcidin expression, ferritin L, and non-haem iron.
      In IL-10(-/-) mice, these changes were less marked or missing for non-haem iron.
      Duodenal ferritin-L and ferroportin increased significantly, while HFE decreased.
      Our results corroborate the conflicting combination of low hepcidin with
      inflammation and without increased intestinal iron absorption. Speculating on
      underlying mechanism, decreased hepcidin may result from stimulated
      erythropoiesis. Unaltered intestinal iron-absorption may compromise between the
      stimulation by increased erythropoiesis and inhibition by local and systemic
      inflammation. The findings suggest intense interaction between counterproductive
      mechanisms and ask for further research. 

PMID- 26302925
TI  - Modulation of copper accumulation and copper-induced toxicity by antioxidants and
      copper chelators in cultured primary brain astrocytes.
AB  - Copper is essential for several important cellular processes, but an excess of
      copper can also lead to oxidative damage. In brain, astrocytes are considered to
      play a pivotal role in the copper homeostasis and antioxidative defence. To
      investigate whether antioxidants and copper chelators can modulate the uptake and
      the toxicity of copper ions in brain astrocytes, we used primary astrocytes as
      cell culture model. These cells accumulated substantial amounts of copper during
      exposure to copper chloride. Copper accumulation was accompanied by a time- and
      concentration-dependent loss in cell viability, as demonstrated by a lowering in
      cellular MTT reduction capacity and by an increase in membrane permeability for
      propidium iodide. During incubations in the presence of the antioxidants
      ascorbate, trolox or ebselen, the specific cellular copper content and the
      toxicity in copper chloride-treated astrocyte cultures were strongly increased.
      In contrast, the presence of the copper chelators bathocuproine disulfonate or
      tetrathiomolybdate lowered the cellular copper accumulation and the copper
      induced as well as the ascorbate-accelerated copper toxicity was fully prevented.
      These data suggest that predominantly the cellular content of copper determines
      copper-induced toxicity in brain astrocytes. 

PMID- 26302926
TI  - Serum copper, zinc and high-sensitivity C-reactive protein in short and long
      sleep duration in ageing men.
AB  - BACKGROUND: Serum levels of zinc and copper have been proposed to associate with
      sleep duration. Mechanisms, such as inflammatory processes, have been suggested
      to relate this association. However, earlier studies have been conducted in small
      sample sizes. Human studies investigating the suggested associations while
      controlling for potential confounding factors are lacking. METHODS: Population
      based data consisted of 2570 men (aged 42-60 years) from Eastern Finland. The
      participants reported an estimate of their sleep duration. The serum levels of
      zinc (S-Zn), copper (S-Cu) and high-sensitivity C-reactive protein (hs-CRP) were
      measured. Analysis of covariance was used for multivariate analyses. RESULTS: S
      Zn levels and Zn/Cu ratio were lowest in <=6h sleep. S-Cu levels were highest in
      >=10h sleep. Elevated levels (>3.0mmol/l) of hs-CRP were observed in <=6h and
      >=10h sleep. After adjustments for age, cumulative smoking history (pack-years),
      alcohol consumption (g/week), Human Population Laboratory depression scale
      scores, physical activity (kcal/day), cardiometabolic syndrome, and
      cardiovascular disease history, sleep duration was significantly associated with
      levels of both S-Cu and hs-CRP. The association with S-Cu remained statistically
      significant following further adjustment for hs-CRP in the same model.
      CONCLUSIONS: Our data suggests an association between S-Cu and sleep duration in
      ageing men. Elevated inflammation (measured as serum hs-CRP) does not explain
      this relationship. Mechanisms underlying the relationship require further
      investigation, as S-Cu may contribute to sleep regulation through pro-oxidative
      processes and copper-dependent N-methyl-d-aspartate receptor activity.

PMID- 26302927
TI  - Zinc and N-acetylcysteine modify mercury distribution and promote increase in
      hepatic metallothionein levels.
AB  - This study investigated the ability of zinc (Zn) and N-acetylcysteine (NAC) in
      preventing the biochemical alterations caused by mercury (Hg) and the retention
      of this metal in different organs. Adult female rats received ZnCl2 (27mg/kg)
      and/or NAC (5mg/kg) or saline (0.9%) subcutaneously and after 24h they received
      HgCl2 (5mg/kg) or saline (0.9%). Twenty-four hours after, they were sacrificed
      and analyses were performed. Hg inhibited hepatic, renal, and blood delta
      aminolevulinic acid dehydratase (delta-ALA-D) activity, decreased renal total
      thiol levels, as well as increased serum creatinine and urea levels and aspartate
      aminotransferase activity. HgCl2-exposed groups presented an important retention
      of Hg in all the tissues analyzed. All pre-treatments demonstrated tendency in
      preventing hepatic delta-ALA-D inhibition, whereas only ZnCl2 showed this effect
      on blood enzyme. Moreover, the combination of these compounds completely
      prevented liver and blood Hg retention. The exposure to Zn and Hg increased
      hepatic metallothionein levels. These results show that Zn and NAC presented
      promising effects against the toxicity caused by HgCl2. 

PMID- 26302928
TI  - High levels of plasma selenium are associated with metabolic syndrome and
      elevated fasting plasma glucose in a Chinese population: A case-control study.
AB  - BACKGROUND: Selenium is important for human health and involved in various
      metabolic processes. Deficiency of selenium associates with increased risk for
      cancer and cardiovascular diseases. There has been an increase use of selenium
      supplements for the treatment of autoimmune thyroid conditions. However, the
      potential biological effects of selenium overload arouse the public concern. The
      aim of this study was to investigate the associations of plasma selenium
      concentrations of adults with metabolic syndrome (MS) in Chinese population.
      METHODS: A matched case-control study including 204 metabolic syndrome patients
      and 204 healthy controls was conducted in 2012. The MS cases were defined
      according to the criteria of Chinese Diabetes Society (CDS). Healthy controls
      without abnormality of metabolic components were matched with cases in age,
      gender and region. Plasma concentrations of selenium were determined by graphite
      furnace atomic absorption spectrometry (GFAAS). Fasting plasma glucose (FPG),
      total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol
      (HDL), and low density lipoprotein cholesterol (LDL) were detected by automatic
      biochemical analyzer. RESULTS: The median levels of plasma selenium in MS group
      were 146.3 (107.3-199.4)MUg/L, which were significantly higher than that in the
      control group (127.4: 95.7-176.0)MUg/L; Plasma levels of selenium were related to
      the risk of MS in dose-response manner. Risk of MS was significantly higher in
      subjects with plasma selenium in the highest tertile (T3: >=176.0MUg/L) compared
      to those in the lowest tertile (T1: <95.7MUg/L) [odds ratio (OR)=2.416 (95% CI:
      1.289-4.526)]. The plasma levels of selenium were positively correlated with
      fasting plasma glucose (FPG) (rs=0.268, P<0.001). Plasma selenium at the median
      (T2: 95.7-176.0MUg/L) or upper tertile (T3: >=176.0MUg/L) was associated with
      increased risk of elevated FPG (defined by FPG>=6.1mmol/L) as compared with the
      lowest tertile (T1: <=95.7MUg/L) [T2 vs. T1, OR=3.487 (1.738-6.996); T3 vs. T1,
      OR=6.245 (3.005-12.981)]. CONCLUSIONS: Higher levels of plasma selenium might
      increase the risk of metabolic syndrome and elevated fasting plasma glucose.
      Selenium supplements should be used with prudence for CVD and cancer prevention.

PMID- 26302929
TI  - Revised reference values for selenium intake.
AB  - The German, Austrian and Swiss nutrition societies are the joint editors of the
      'reference values for nutrient intake'. They have revised the reference values
      for the intake of selenium and published them in February 2015. The saturation of
      selenoprotein P (SePP) in plasma is used as a criterion for the derivation of
      reference values for selenium intake in adults. For persons from selenium
      deficient regions (China) SePP saturation was achieved with a daily intake of
      49MUg of selenium. When using the reference body weights the D-A-CH reference
      values are based upon, the resulting estimated value for selenium intake is
      70MUg/day for men and 60MUg/day for women. The estimated value for selenium
      intake for children and adolescents is extrapolated using the estimated value for
      adults in relation to body weight. For infants aged 0 to under 4 months the
      estimated value of 10MUg/day was derived from the basis of selenium intake via
      breast milk. For infants aged 4 to under 12 months this estimated value was used
      and taking into account the differences regarding body weight an estimated value
      of 15MUg/day was derived. For lactating women compared to non-lactating women a
      higher reference value of 75MUg/day is indicated due to the release of selenium
      with breast milk. The additional selenium requirement for pregnant women is
      negligible, so that no increased reference value is indicated. 

PMID- 26302930
TI  - Toxicity of organic and inorganic mercury species in differentiated human neurons
      and human astrocytes.
AB  - Organic mercury (Hg) species exert their toxicity primarily in the central
      nervous system. The food relevant Hg species methylmercury (MeHg) has been
      frequently studied regarding its neurotoxic effects in vitro and in vivo.
      Neurotoxicity of thiomersal, which is used as a preservative in medical
      preparations, is to date less characterised. Due to dealkylation of organic Hg or
      oxidation of elemental Hg, inorganic Hg is present in the brain albeit these
      species are not able to readily cross the blood brain barrier. This study
      compared for the first time toxic effects of organic MeHg chloride (MeHgCl) and
      thiomersal as well as inorganic mercury chloride (HgCl2) in differentiated human
      neurons (LUHMES) and human astrocytes (CCF-STTG1). The three Hg species differ in
      their degree and mechanism of toxicity in those two types of brain cells.
      Generally, neurons are more susceptible to Hg species induced cytotoxicity as
      compared to astrocytes. This might be due to the massive cellular mercury uptake
      in the differentiated neurons. The organic compounds exerted stronger cytotoxic
      effects as compared to inorganic HgCl2. In contrast to HgCl2 exposure, organic Hg
      compounds seem to induce the apoptotic cascade in neurons following low-level
      exposure. No indicators for apoptosis were identified for both inorganic and
      organic mercury species in astrocytes. Our studies clearly demonstrate species
      specific toxic mechanisms. A mixed exposure towards all Hg species in the brain
      can be assumed. Thus, prospectively coexposure studies as well as cocultures of
      neurons and astrocytes could provide additional information in the investigation
      of Hg induced neurotoxicity. 

PMID- 26302931
TI  - The role of chemical speciation, chemical fractionation and calcium disruption in
      manganese-induced developmental toxicity in zebrafish (Danio rerio) embryos.
AB  - Manganese (Mn) is an essential nutrient that can be toxic in excess
      concentrations, especially during early development stages. The mechanisms of Mn
      toxicity is still unclear, and little information is available regarding the role
      of Mn speciation and fractionation in toxicology. We aimed to investigate the
      toxic effects of several chemical forms of Mn in embryos of Danio rerio exposed
      during different development stages, between 2 and 122h post fertilization. We
      found a stage-specific increase of lethality associated with hatching and removal
      of the chorion. Mn(II), ([Mn(H2O)6](2+)) appeared to be the most toxic species to
      embryos exposed for 48h, and Mn(II) citrate was most toxic to embryos exposed for
      72 and/or 120h. Manganese toxicity was associated with calcium disruption,
      manganese speciation and metal fractionation, including bioaccumulation in
      tissue, granule fractions, organelles and denaturated proteins. 

PMID- 26302932
TI  - Elevated expression of T-bet in mycobacterial antigen-specific CD4(+) T cells
      from patients with tuberculosis.
AB  - T-bet is a T-box transcriptional factor that controls the differentiation and
      effector functions of CD4 T cells. In this study, we studied the role of T-bet in
      regulating CD4(+) T cell immunity against tuberculosis (TB). T-bet expression in
      Mycobacterium tuberculosis antigen-specific CD4(+) T cells was significantly
      higher in patients with active TB than in individuals with latent TB infection
      (p<0.0001). Comparison of T-bet expression in TCM and TEM subsets showed that
      CD4(+)T-bet(+)M. tuberculosis antigen-specific CD4(+) T cells had significantly
      lower frequency of TCM (p=0.003) and higher frequency of TEM (p=0.003) than
      CD4(+)T-bet(-) cells. The expression of PD-1 in antigen-specific CD4(+) T cells
      was significantly higher in patients with TB than in individuals with latent TB
      infection (p=0.006). CD4(+)CD154(+)T-bet(+) T cells had significantly higher
      expression of PD-1 than CD4(+)CD154(+)T-bet(-) T cells (p=0.0028). It is
      concluded that T-bet expression might be associated with differentiation into
      effector memory cells and PD-1 expression in mycobacterial antigen-specific
      CD4(+) T cells. 

PMID- 26302934
TI  - PLD1 activation mediates Amb a 1-induced Th2-associated cytokine expression via
      the JNK/ATF-2 pathway in BEAS-2B cells.
AB  - The purpose of this study was to identify the role of phospholipase D1 (PLD1) in
      Amb a 1-induced IL-5 and IL-13 expression. When BEAS-2B cells were stimulated
      with Amb a 1, PLD activity increased, and knockdown of PLD1 decreased Amb a 1
      induced IL-5 and IL-13 expression. Amb a 1 also activated the PLCgamma/p70S6K/JNK
      pathway. Furthermore, Amb a 1-induced PLD activation was also attenuated by
      PLCgamma inhibition, and knockdown of PLD1 decreased Amb a 1-induced activation
      of P70S6K and JNK. When ATF-2 activity was blocked with ATF-2 siRNA, Amb a 1
      induced IL-5 and IL-13 expression was completely abolished, indicating that ATF-2
      is a transcriptional factor required for the expression of IL-5 and IL-13 in
      response to Amb a 1. Taken together, we suggest that PLD1 acts as an important
      regulator in Amb a 1-induced expression of IL-5 and IL-13 via a
      PLCgamma/p70S6K/JNK/ATF-2 pathway in BEAS-2B cells. 

PMID- 26302933
TI  - HBD-3 induces NK cell activation, IFN-gamma secretion and mDC dependent cytolytic
      function.
AB  - We previously showed that human beta defensin-3 (hBD-3) activates mDC via TLR1/2.
      Here we investigated the effects of hBD-3 on NK cell activation state and
      effector functions. We observed that hBD-3 activates PBMC to secrete IFN-gamma
      and kill K562 and HUH hepatoma target cells in an NK dependent fashion, and both
      TLR1/2 and CCR2 are involved. TLR1, TLR2 and CCR2 were expressed on NK cells, and
      in purified NK culture experiments we observed hBD-3 to directly act on NK cells,
      resulting in CD69 upregulation and IFNgamma secretion. We also observed mDC-hBD-3
      enhanced NK cytolytic activity and IFNgamma production. These results implicate
      hBD-3 in its ability to directly activate NK cells and increase NK cell effector
      function, as well as promote mDC-dependent NK activity. HBD-3 may therefore act
      as a mediator of innate cell interactions that result in bridging of innate and
      adaptive immunity. 

PMID- 26302936
TI  - Complex craniofacial advancement in paediatric patients: Piezoelectric and
      traditional technique evaluation.
AB  - PURPOSE: The piezoelectric device allows bone cutting without damaging the
      surrounding soft tissues. The purpose of this study was to assess the role of
      this surgical instrument in paediatric craniofacial surgery in terms of safety
      and surgical outcomes. METHODS: Thirteen consecutive paediatric patients
      underwent craniofacial Le Fort osteotomies type III and IV. The saw was used on
      the right side in seven patients and on the left side in six patients; the
      piezoelectric instrument was used on the right side in six patients and on the
      left side in seven patients. Intraoperative blood loss, surgical procedure
      length, incision precision, postoperative haematoma and swelling, and nerve
      impairment were evaluated to compare the outcomes of both procedures. RESULTS: A
      longer surgical procedure was observed in 28% of the patients when using the
      piezoelectric device (p = 0.032), with an intraoperative blood loss reduction of
      18% (p = 0.156). Greater precision in bone cutting was reported, together with a
      reduction in the requirement to protect and incise adjacent soft tissues during
      piezoelectric osteotomies. There was a lower incidence of postoperative haematoma
      and swelling following piezo-osteotomy, and a significant reduction in
      postoperative nerve impairment (p = 0.002). CONCLUSIONS: The ultrasonic surgical
      device guaranteed a clean bone cut, preserving the integrity of the adjacent soft
      tissues beneath the bone. Although the time required for a piezoelectric
      osteotomy was longer, the total operation time remained approximately the same.
      In conclusion, the device's lack of power appears to be a minor problem compared
      with the advantages, and an ultrasonic device could be considered a valuable
      instrument for paediatric craniofacial advancement.

PMID- 26302935
TI  - Stage III nasopharyngeal angiofibroma: Improving results with endoscopic-assisted
      midfacial degloving and modification to the Fisch staging system.
AB  - OBJECTIVES: To study outcomes with endoscopic-assisted midfacial degloving for
      Fisch stage III nasopharyngeal angiofibroma and propose a new staging system.
      DESIGN: Retrospective study of patients with Fisch stage III juvenile
      nasopharyngeal angiofibroma (JNA) including preoperative angiography,
      intraoperative blood loss and residue/recurrence following surgery. SETTING:
      Tertiary care superspecialty referral center. PARTICIPANTS: Fifteen consecutive
      patients with Fisch stage III JNA undergoing operations over a period of 18
      months. MAIN OUTCOME MEASURES: Preoperative angiography details, intraoperative
      blood loss, residue/recurrence, complications of surgery. CONCLUSIONS:
      Transarterial embolization with particulate agents followed by endoscopic
      assisted midfacial degloving provides excellent outcomes with Fisch stage III
      JNAs. The modified Fisch staging system proposed would allow better preoperative
      evaluation and comparison of outcomes with different treatment options for stage
      III JNAs.

PMID- 26302937
TI  - Integration of oncologic margins in three-dimensional virtual planning for head
      and neck surgery, including a validation of the software pathway.
AB  - PURPOSE: Three-dimensional (3D) virtual planning of reconstructive surgery, after
      resection, is a frequently used method for improving accuracy and predictability.
      However, when applied to malignant cases, the planning of the oncologic resection
      margins is difficult due to visualisation of tumours in the current 3D planning.
      Embedding tumour delineation on a magnetic resonance image, similar to the
      routinely performed radiotherapeutic contouring of tumours, is expected to
      provide better margin planning. A new software pathway was developed for
      embedding tumour delineation on magnetic resonance imaging (MRI) within the 3D
      virtual surgical planning. MATERIAL AND METHODS: The software pathway was
      validated by the use of five bovine cadavers implanted with phantom tumour
      objects. MRI and computed tomography (CT) images were fused and the tumour was
      delineated using radiation oncology software. This data was converted to the 3D
      virtual planning software by means of a conversion algorithm. Tumour volumes and
      localization were determined in both software stages for comparison analysis. The
      approach was applied to three clinical cases. RESULTS: A conversion algorithm was
      developed to translate the tumour delineation data to the 3D virtual plan
      environment. The average difference in volume of the tumours was 1.7%.
      CONCLUSION: This study reports a validated software pathway, providing multi
      modality image fusion for 3D virtual surgical planning.

PMID- 26302938
TI  - DNA methylation analysis by bisulfite next-generation sequencing for early
      detection of oral squamous cell carcinoma and high-grade squamous intraepithelial
      lesion from oral brushing.
AB  - PURPOSE: Oral squamous cell carcinoma (OSCC) is commonly preceded by oral
      potentially malignant lesions (OPML). The aim of the present study was to assess,
      by bisulfite next-generation sequencing (NGS), the methylation status of a list
      of candidate genes obtained from oral brushings to early detect OPML and OSCC.
      MATERIAL AND METHODS: Oral brushing specimens from 11 OSCC, 11 high-grade
      squamous intraepithelial lesions (HG-SIL), 9 low-grade SIL (LG-SIL), 9 oral
      lichen planus (OLP), and 8 healthy donors were included in this study. We
      investigated, by means of bisulfite NGS, the promoter of GP1BB, ZAP70, KIF1A,
      p16[CDKN2A], CDH1, miR137, and miR375. Statistical significance between lesions
      and a pool of healthy donors were evaluated with the Mann-Whitney U test.
      RESULTS: ZAP70 was found to be hypermethylated in 100% of OSCC and HG-SIL and in
      28.6% of LG-SIL. GP1BB hypomethylation was detected in 90.9% OSCC and HG-SIL and
      in 37.5% of LG-SIL. MiR137 was hypermethylated in 100% of OLP, 44.4% of OSCC, 40%
      HG-SIL, and 25% LG-SIL. KIF1A hypermethylation was found to be associated with
      TP53 mutations (p < 0.0001). CONCLUSION: In the present preliminary cohort of
      patients, DNA methylation analysis of GP1BB and ZAP70 seems to be a promising
      noninvasive tool for early detection of OSCC and HG SIL from oral brushing
      specimens.

PMID- 26302939
TI  - Regenerative medicine in the treatment of alveolar cleft defect: A systematic
      review of the literature.
AB  - Despite a possible risk of donor site morbidity, autogenous bone grafting is
      considered the gold standard treatment for human alveolar cleft defect. Tissue
      engineering methods have recently been investigated with the aim of minimizing
      donor site morbidities. Here we systematically review the various tissue
      engineering methods applied to human alveolar cleft defects. An electronic search
      was conducted in the PubMed database up to March 2014. Tissue engineering studies
      on human alveolar subjects were included, and experiments that did not report
      quality or quantity of new regenerated bone were excluded. Twenty human
      experiments were included in our review. Regenerative techniques for alveolar
      cleft bone reconstruction were divided into cell therapy, growth factor
      application, and a combination of both cell therapy and growth factor. Using
      these three regenerative methods, a wide range of new bone formation percentages
      were reported. Due to insufficient evidence and controlled clinical trials, the
      treatment efficacy of tissue engineering in alveolar cleft bone defects could not
      be determined. Well-designed controlled studies are needed so that detailed
      outcomes can be properly compared. 

PMID- 26302940
TI  - Financial incentives in health: New evidence from India's Janani Suraksha Yojana.
AB  - This paper studies the health effects of one of the world's largest demand-side
      financial incentive programmes--India's Janani Suraksha Yojana. Our difference-in
      difference estimates exploit heterogeneity in the implementation of the financial
      incentive programme across districts. We find that cash incentives to women were
      associated with increased uptake of maternity services but there is no strong
      evidence that the JSY was associated with a reduction in neonatal or early
      neonatal mortality. The positive effects on utilisation are larger for less
      educated and poorer women, and in places where the cash payment was most
      generous. We also find evidence of unintended consequences. The financial
      incentive programme was associated with a substitution away from private health
      providers, an increase in breastfeeding and more pregnancies. These findings
      demonstrate the potential for financial incentives to have unanticipated effects
      that may, in the case of fertility, undermine the programme's own objective of
      reducing mortality.

PMID- 26302941
TI  - What else could be done for management of cancer patients in ED? Challenges and
      suggestions (cancer patients and emergency service).

PMID- 26302942
TI  - Factors associated with ciprofloxacin-resistant Escherichia coli urinary tract
      infections in discharged ED patients.
AB  - BACKGROUND: We sought to identify factors associated with Escherichia coli
      resistance to ciprofloxacin among discharged emergency department (ED) patient
      visits treated for a urinary tract infection (UTI). We hypothesized that specific
      historical factors available upon ED presentation would be associated with
      increased odds of ciprofloxacin resistance in this population. METHODS: We
      conducted a retrospective, observational cohort study of consecutive discharged
      adult ED patient visits with a primary diagnosis of UTI caused by E coli to a
      single center from 2011 to 2014. Two investigators separately abstracted to a
      preconstructed data collection form the following independent variables on each
      included visit: patient age, sex, residence, active immunosuppressive condition
      or medication, chronic indwelling Foley catheter, hospitalization or antibiotic
      use within 90 days prior to presentation, and history of recurrent UTIs. We used
      multivariable logistic regression after taking into account colinearity to
      identify those independent variables associated with increased odds of
      ciprofloxacin resistance and report descriptive characteristics of the study
      cohort, odds ratios (ORs) with 95% confidence interval (CI) and model strength.
      RESULTS: Age at least 65 years (OR, 3.15; 95% CI, 1.44-6.87; P=.004), recurrent
      UTI (OR, 6.23; 95% CI, 2.38-16.30; P<.001), and recent hospitalization (OR, 3.99;
      95% CI, 1.56-10.23; P=.004) were significantly associated with ciprofloxacin
      resistant E coli UTIs in relevant visits. CONCLUSION: In this single-center
      study, age at least 65 years, recurrent UTI, and recent hospitalization were most
      clearly associated with increased odds of ciprofloxacin-resistant UTIs in
      discharged adult ED patient visits. If validated, these factors should suggest
      that alternative antimicrobial agents should be considered in the treatment of
      this condition among discharged adult ED patients.

PMID- 26302943
TI  - Atomically controlled substitutional boron-doping of graphene nanoribbons.
AB  - Boron is a unique element in terms of electron deficiency and Lewis acidity.
      Incorporation of boron atoms into an aromatic carbon framework offers a wide
      variety of functionality. However, the intrinsic instability of organoboron
      compounds against moisture and oxygen has delayed the development. Here, we
      present boron-doped graphene nanoribbons (B-GNRs) of widths of N=7, 14 and 21 by
      on-surface chemical reactions with an employed organoboron precursor. The
      location of the boron dopant is well defined in the centre of the B-GNR,
      corresponding to 4.8 atom%, as programmed. The chemical reactivity of B-GNRs is
      probed by the adsorption of nitric oxide (NO), which is most effectively trapped
      by the boron sites, demonstrating the Lewis acid character. Structural properties
      and the chemical nature of the NO-reacted B-GNR are determined by a combination
      of scanning tunnelling microscopy, high-resolution atomic force microscopy with a
      CO tip, and density functional and classical computations. 

PMID- 26302945
TI  - Interaural stimulation timing in single sided deaf cochlear implant users.
AB  - The interaural time difference (ITD) is an important cue for the localization of
      sounds. ITD changes as little as 10 MUs can be detected by the human auditory
      system. By provision of one ear with a cochlear implant (CI) ITD are altered due
      to the partial replacement of the peripheral auditory system. A hearing aid (HA),
      in contrast, does not replace but adds a processing delay component to the
      peripheral auditory system extending ITD. The aim of the present study was to
      quantify interaural stimulation timing between these different modalities to
      estimate the need for central auditory temporal compensation in single sided deaf
      CI users or bimodal CI/HA users. For this purpose, wave V latencies of auditory
      brainstem responses evoked either acoustically (ABR) or electrically via the CI
      (EABR) have been measured. The sum of delays consisting of CI signal processing
      measured in the MED-EL OPUS2 audio processor and EABR wave V latencies evoked on
      different intracochlear sites allowed an estimation of the entire CI channel
      specific delay for MED-EL MAESTRO CI systems. We compared these values with ABR
      wave V latencies measured in the contralateral normal hearing or HA provided ear
      in different frequency bands. The results showed that EABR wave V latencies were
      consistently shorter than those evoked acoustically in the unaided normal hearing
      ear. Thus, artificial delays within the audio processor can be implemented to
      adjust interaural stimulation timing. The currently implemented group delays in
      the MED-EL CI system turned out to be reasonably similar to those of the unaided
      ear. For adjustment of CI and contralateral HA, in contrast, an adjustable
      additional across-frequency delay in the range of 1-11 ms implemented in the CI
      would be required. Especially for bimodal CI/HA users the adjustment of
      interaural stimulation timing may induce improved binaural hearing, reduced need
      for central auditory temporal compensation and increased acceptance of the CI/HA
      provision. 

PMID- 26302944
TI  - Major predictors and management of small-bowel angioectasia.
AB  - BACKGROUND: Small-bowel angioectasias are frequently diagnosed with capsule
      endoscopy (CE) or balloon endoscopy however, major predictors have not been
      defined and the indications for endoscopic treatment have not been standardized.
      The aim of this study was to evaluate the predictors and management of small
      bowel angioectasia. METHODS: Among patients with obscure gastrointestinal
      bleeding (OGIB) who underwent both CE and double-balloon endoscopy at our
      institution, we enrolled 64 patients with small-bowel angioectasia (angioectasia
      group) and 97 patients without small-bowel angioectasia (non-angioectasia group).
      The angioectasia group was subdivided into patients with type 1a angioectasia (35
      cases) and type 1b angioectasia (29 cases) according to the Yano-Yamamoto
      classification. Patient characteristics, treatment, and outcomes were evaluated.
      RESULTS: Age (P = 0.001), cardiovascular disease (P = 0.002), and liver cirrhosis
      (P = 0.003) were identified as significant predictors of small-bowel
      angioectasia. Multivariate logistic regression analysis identified cardiovascular
      disease (odds ratio 2.86; 95% confidence interval, 1.35-6.18) and liver cirrhosis
      (odds ratio 4.81; 95% confidence interval, 1.79-14.5) as independent predictors
      of small-bowel angioectasia. Eleven type 1a cases without oozing were treated
      conservatively, and 24 type 1a cases with oozing were treated with polidocanol
      injection (PDI). Re-bleeding occurred in two type 1a cases (6%). Seventeen type
      1b cases were treated with PDI and 12 type 1b cases were treated with PDI
      combined with argon plasma coagulation (APC) or clipping. Re-bleeding occurred in
      five type 1b cases (17%) that resolved after additional endoscopic hemostasis in
      all cases. There was one adverse event from endoscopic treatment (1.6%).
      CONCLUSIONS: Cardiovascular disease and liver cirrhosis were significant
      independent major predictors of small-bowel angioectasia. Type 1a angioectasias
      with oozing are indicated for PDI and type 1b angioectasias are indicated for PDI
      with APC or clipping.

PMID- 26302946
TI  - Enhanced audio-visual interactions in the auditory cortex of elderly cochlear
      implant users.
AB  - Auditory deprivation and the restoration of hearing via a cochlear implant (CI)
      can induce functional plasticity in auditory cortical areas. How these plastic
      changes affect the ability to integrate combined auditory (A) and visual (V)
      information is not yet well understood. In the present study, we used
      electroencephalography (EEG) to examine whether age, temporary deafness and
      altered sensory experience with a CI can affect audio-visual (AV) interactions in
      post-lingually deafened CI users. Young and elderly CI users and age-matched NH
      listeners performed a speeded response task on basic auditory, visual and audio
      visual stimuli. Regarding the behavioral results, a redundant signals effect,
      that is, faster response times to cross-modal (AV) than to both of the two
      modality-specific stimuli (A, V), was revealed for all groups of participants.
      Moreover, in all four groups, we found evidence for audio-visual integration.
      Regarding event-related responses (ERPs), we observed a more pronounced visual
      modulation of the cortical auditory response at N1 latency (approximately 100 ms
      after stimulus onset) in the elderly CI users when compared with young CI users
      and elderly NH listeners. Thus, elderly CI users showed enhanced audio-visual
      binding which may be a consequence of compensatory strategies developed due to
      temporary deafness and/or degraded sensory input after implantation. These
      results indicate that the combination of aging, sensory deprivation and CI
      facilitates the coupling between the auditory and the visual modality. We suggest
      that this enhancement in multisensory interactions could be used to optimize
      auditory rehabilitation, especially in elderly CI users, by the application of
      strong audio-visually based rehabilitation strategies after implant switch-on. 

PMID- 26302947
TI  - Comparison of four digital PCR platforms for accurate quantification of DNA copy
      number of a certified plasmid DNA reference material.
AB  - Digital polymerase chain reaction (dPCR) is a unique approach to measurement of
      the absolute copy number of target DNA without using external standards. However,
      the comparability of different dPCR platforms with respect to measurement of DNA
      copy number must be addressed before dPCR can be classified fundamentally as an
      absolute quantification technique. The comparability of four dPCR platforms with
      respect to accuracy and measurement uncertainty was investigated by using a
      certified plasmid reference material. Plasmid conformation was found to have a
      significant effect on droplet-based dPCR (QX100 and RainDrop) not shared with
      chip-based QuantStudio 12k or BioMark. The relative uncertainty of partition
      volume was determined to be 0.7%, 0.8%, 2.3% and 2.9% for BioMark, QX100,
      QuantStudio 12k and RainDrop, respectively. The measurements of the certified
      pNIM-001 plasmid made using the four dPCR platforms were corrected for partition
      volume and closely consistent with the certified value within the expended
      uncertainty. This demonstrated that the four dPCR platforms are of comparable
      effectiveness in quantifying DNA copy number. These findings provide an
      independent assessment of this method of determining DNA copy number when using
      different dPCR platforms and underline important factors that should be taken
      into consideration in the design of dPCR experiments. 

PMID- 26302948
TI  - Phylogenetic analysis of the winter geometrid genus Inurois reveals repeated
      reproductive season shifts.
AB  - Winter geometrid moths belonging to the genus Inurois comprise nine species that
      reproduce during early winter, three species that reproduce in late winter, and
      polymorphic species with genetically diverged early and late winter populations
      that co-occur widely across the species' range. In our previous studies, we
      demonstrated that differences in reproductive timing resulted in allochronic
      reproductive isolation between sympatric populations. In the present study, to
      assess the evolutionary pattern of reproductive timing within the genus, we
      determined the phylogenetic relationships among species using nuclear and
      mitochondrial gene sequences. Nuclear gene tree showed that reproductive season
      shifts occurred independently in four of 13 divergence events. In two divergence
      events, allochronic sister lineages were formed in sympatry, suggesting that the
      segregation of the reproductive season was associated with diversification in the
      genus Inurois. We also found that the mitochondrial gene tree was quite different
      from the nuclear gene tree and that mitochondrial introgression may have occurred
      in a few cases. Although it remains unclear whether early and late winter species
      actually have hybridized with each other and how strong or stable is the
      reproductive isolation provided by the reproductive season segregation, our study
      illuminates the potential importance of allochronic isolation in the
      diversification process of the genus Inurois. 

PMID- 26302949
TI  - Molecular phylogeny of Pompilinae (Hymenoptera: Pompilidae): Evidence for rapid
      diversification and host shifts in spider wasps.
AB  - Pompilinae is one of the largest subfamilies of spider wasps (Pompilidae). Most
      pompilines are generalist spider predators at the family level, but some taxa
      exhibit ecological specificity (i.e., to spider-host guild). Here we present the
      first molecular phylogenetic analysis of Pompilinae, toward the aim of evaluating
      the monophyly of tribes and genera. We further test whether changes in the rate
      of diversification are associated with host-guild shifts. Molecular data were
      collected from five nuclear loci (28S, EF1-F2, LWRh, Wg, Pol2) for 76 taxa in 39
      genera. Data were analyzed using maximum likelihood (ML) and Bayesian inference
      (BI). The phylogenetic results were compared with previous hypotheses of
      subfamilial and tribal classification, as well as generic relationships in the
      subfamily. The classification of Pompilus and Agenioideus is also discussed. A
      Bayesian relaxed molecular clock analysis was used to examine divergence times.
      Diversification rate-shift tests accounted for taxon-sampling bias using ML and
      BI approaches. Ancestral host family and host guild were reconstructed using MP
      and ML methods. Ancestral host guild for all Pompilinae, for the ancestor at the
      node where a diversification rate-shift was detected, and two more nodes back in
      time was inferred using BI. In the resulting phylogenies, Aporini was the only
      previously proposed monophyletic tribe. Several genera (e.g., Pompilus,
      Microphadnus and Schistonyx) are also not monophyletic. Dating analyses produced
      a well-supported chronogram consistent with topologies from BI and ML results.
      The BI ancestral host-use reconstruction inferred the use of spiders belonging to
      the guild "other hunters" (frequenting the ground and vegetation) as the
      ancestral state for Pompilinae. This guild had the highest probability for the ML
      reconstruction and was equivocal for the MP reconstruction; various switching
      events to other guilds occurred throughout the evolution of the group. The
      diversification of Pompilinae shows one main rate-shift coinciding with a shift
      to ground-hunter spiders, as reconstructed by the BI ancestral character-state
      analysis. 

PMID- 26302950
TI  - Geographic isolation drives divergence of uncorrelated genetic and song variation
      in the Ruddy-capped Nightingale-Thrush (Catharus frantzii; Aves: Turdidae).
AB  - Montane barriers influence the evolutionary history of lineages by promoting
      isolation of populations. The effects of these historical processes are evident
      in patterns of differentiation among extant populations, which are often
      expressed as genetic and behavioral variation between populations. We
      investigated the effects of geographic barriers on the evolutionary history of a
      Mesoamerican bird by studying patterns of genetic and vocal variation in the
      Ruddy-capped Nightingale-Thrush (Turdidae: Catharus frantzii), a non-migratory
      oscine bird that inhabits montane forests from central Mexico to Panama. We
      reconstructed the phylogeographic history and estimated divergence times between
      populations using Bayesian and maximum likelihood methods. We found strong
      support for the existence of four mitochondrial lineages of C. frantzii
      corresponding to isolated mountain ranges: Sierra Madre Oriental; Sierra Madre
      del Sur; the highlands of Chiapas, Guatemala, and El Salvador; and the Talamanca
      Cordillera. Vocal features in C. frantzii were highly variable among the four
      observed clades, but vocal variation and genetic variation were uncorrelated.
      Song variation in C. frantzii suggests that sexual selection and cultural drift
      could be important factors driving song differentiation in C. frantzii.

PMID- 26302951
TI  - Reflectance Confocal Microscopy Features of Focal Dermal Mucinosis Differ from
      Those Described for Basal Cell Carcinoma: Report of Two Cases.
AB  - The purpose of this study was to describe the reflectance confocal microscopy
      (RCM) features of focal dermal mucinosis (FDM). The entity clinically and
      dermatoscopically mimics other diagnostic entities, most notably nonpigmented
      basal cell carcinoma. We describe two cases that highlight the dermatoscopic, RCM
      and histopathological attributes of FDM. RCM features such as dermal foci of
      dense collagen bundles oriented in the same direction, foci of haphazardly
      oriented thin collagen fibers separated by dark structureless areas and the
      absence of dark silhouettes and tumor islands are clues for FDM diagnosis. The
      FDM cases described here present consistent and particular RCM findings that
      appear to correlate well with the histopathological features of FDM. Therefore,
      RCM is a promising technology in diagnosing skin lesions and it use can avoid
      invasive procedures. 

PMID- 26302952
TI  - Risk factors of ifosfamide-related encephalopathy in adult patients with cancer:
      A retrospective analysis.
AB  - BACKGROUND/PURPOSE: Ifosfamide, a widely used chemotherapeutic agent, has been
      frequently associated with encephalopathy. A larger-scale study was conducted to
      identify risk factors of ifosfamide-related encephalopathy, including hepatic
      function. METHODS: Adult patients who had completed at least one cycle of
      ifosfamide between January 2008 and December 2010 were included. Those with renal
      failure or liver failure were excluded. Data were collected through chart review.
      Patients with encephalopathy and patients without encephalopathy were compared on
      age, Eastern Cooperative Oncology Group (ECOG) performance status (PS), baseline
      serum creatinine (SCr) level, albumin level, white blood cell count, liver
      function, brain metastasis, and dosage of ifosfamide. Chi-square test or Fisher's
      exact test, Student t test, and univariate and multivariate logistic regressions
      were used for analysis. RESULTS: This study enrolled 337 patients. Thirty-eight
      patients (11%) had ifosfamide-related encephalopathy. They had poorer ECOG PS;
      higher SCr level, white blood cell count, and aspartate aminotransferase level;
      and lower serum albumin level compared with patients without encephalopathy.
      Ifosfamide dosage, brain metastasis, and age were not significant risk factors.
      Multivariate analysis indicated that only ECOG PS, SCr level, and albumin level
      contributed significantly to the risk. CONCLUSION: To date, this is the largest
      scale study to have analyzed the risk factors of ifosfamide-related
      encephalopathy. This study confirms that an ECOG PS of 2-4 and increased SCr
      level are significant risk factors of ifosfamide-related encephalopathy, whereas
      increased albumin level decreases the risk, consistent with previous reports.
      Higher aspartate aminotransferase levels have no significant impact. In contrast
      to previous studies, ifosfamide dosage and brain metastasis are not significant
      contributing factors.

PMID- 26302953
TI  - The successful search for genetic loci associated with depression.
AB  - Major depressive disorder is among the leading causes of disease burden and
      disability, as well as a major public health concern worldwide. Despite its
      substantial heritability, no robustly replicated genetic risk loci had been found
      until recently. Now, a new study has identified, and replicated, two variants
      associated with an increased risk for this disorder. The success of this study
      appears to lie in the use of low-coverage sequencing, instead of microarrays, and
      in minimizing phenotypic and genetic heterogeneity. 

PMID- 26302955
TI  - Controlling wave-vector of propagating surface plasmon polaritons on single
      crystalline gold nanoplates.
AB  - Surface plasmon polaritons (SPPs) propagating at metal nanostructures play an
      important role in breaking the diffraction limit. Chemically synthesized single
      crystalline metal nanoplates with atomically flat surfaces provide favorable
      features compared with traditional polycrystalline metal films. The excitation
      and propagation of leaky SPPs on micrometer sized (10-20 MUm) and thin (30 nm)
      gold nanoplates are investigated utilizing leakage radiation microscopy. By
      varying polarization and excitation positions of incident light on apexes of
      nanoplates, wave-vector (including propagation constant and propagation
      direction) distributions of leaky SPPs in Fourier planes can be controlled,
      indicating tunable SPP propagation. These results hold promise for potential
      development of chemically synthesized single-crystalline metal nanoplates as
      plasmonic platforms in future applications. 

PMID- 26302954
TI  - Long-term effect of early postnatal overnutrition on insulin resistance and serum
      fatty acid profiles in male rats.
AB  - BACKGROUND: Increasing evidence suggests that overnutrition during the early
      postnatal period, a critical window of development, increases the risk of adult
      onset obesity and insulin resistance. In this study, we investigated the impact
      of overnutrition during the suckling period on body weight, serum biochemistry
      and serum fatty acid metabolomics in male rats. METHODS: Rats raised in small
      litters (SL, 3 pups/dam) and normal litters (NL, 10 pups/dam) were used to model
      early postnatal overnutrition and control, respectively. Serum glucose,
      triglyceride, high-density lipoprotein-cholesterol, free fatty acid, insulin and
      leptin concentrations were assayed using standard biochemical techniques. Serum
      fatty acids were identified and quantified using a gas chromatography-mass
      spectrometry-based metabolomic approach. mRNA and protein levels of key
      components of the insulin receptor signaling pathway were measured in epididymal
      fat and gastrocnemius muscle by quantitative PCR and western blotting. RESULTS:
      SL rats were 37.3 % and 15.1 % heavier than NL rats at weaning and 16-weeks-old,
      respectively. They had increased visceral fat mass, adult-onset insulin
      resistance and glucose intolerance as well as elevated serum levels of free fatty
      acids and triglycerides. All detectable fatty acids were elevated in the serum of
      SL pups at weaning compared to NL controls, and significant increases in the
      levels of four fatty acids (palmitic acid, palmitoleic acid, oleic acid and
      arachidonic acid) persisted into adulthood. Moreover, a significantly positive
      correlation was identified between an insulin resistance index (HOMA-IR) and
      concentrations of myristic, palmitic, palmitoleic and oleic acid in serum at
      postnatal 16 weeks. Early postnatal overnutrition also resulted in a significant
      downregulation of insulin receptor substrate-1 (Irs-1), protein kinase B (Akt2)
      and glucose transporter 4 (Glut4) at the protein level in epididymal fat of SL
      rats at 16 weeks, accompanied by decreased mRNA levels for Irs-1 and Glut4. In
      gastrocnemius muscle, Akt2 and Glut4 mRNA and Glut4 protein levels were
      significantly decreased in SL rats. CONCLUSIONS: This study demonstrates that
      early postnatal overnutrition can have long-lasting effects on body weight and
      serum fatty acid profiles and can lead to impaired insulin signaling pathway in
      visceral white adipose tissue and skeletal muscle, which may play a major role in
      IR.

PMID- 26302957
TI  - An Ecosystems and Vulnerable Populations Perspective on Solastalgia and
      Psychological Distress After a Wildfire.
AB  - We studied the relationship between psychological distress and relative resource
      and risk predictors, including loss of solace from the landscape (solastalgia),
      one year after the Wallow Fire, in Arizona, United States. Solastalgia refers to
      the distress caused by damage to the surrounding natural environment and it has
      not been examined for its relationship to psychological health. Doing so opens
      avenues of research that inquire into how land management might be able to
      support improved community resilience and psychological health outcomes after a
      wildfire. In 2012, we conducted a household survey mailed to all 1387 households
      in the five communities surrounding the fire. The Kessler Psychological Distress
      Scale assessed psychological distress. In the multivariate analysis, higher
      solastalgia score and an adverse financial impact of the fire were associated
      with clinically significant psychological distress. Annual household income >=
      $80,000 and a higher family functioning score were associated with less
      psychological distress. Part-time residents were no more likely to have
      psychological distress than full-time residents. We conclude that dramatic
      transformation of a landscape by an environmental event such as a wildfire can
      reduce its value as a source of solace. These results call for novel post
      wildfire community recovery interventions that wed forest management and
      community psychology.

PMID- 26302956
TI  - Rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic
      Dysregulation (ROHHAD): exome sequencing of trios, monozygotic twins and tumours.
AB  - BACKGROUND: Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation,
      and Autonomic Dysregulation (ROHHAD) is thought to be a genetic disease caused by
      de novo mutations, though causative mutations have yet to be identified. We
      searched for de novo coding mutations among a carefully-diagnosed and clinically
      homogeneous cohort of 35 ROHHAD patients. METHODS: We sequenced the exomes of
      seven ROHHAD trios, plus tumours from four of these patients and the unaffected
      monozygotic (MZ) twin of one (discovery cohort), to identify constitutional and
      somatic de novo sequence variants. We further analyzed this exome data to search
      for candidate genes under autosomal dominant and recessive models, and to
      identify structural variations. Candidate genes were tested by exome or Sanger
      sequencing in a replication cohort of 28 ROHHAD singletons. RESULTS: The analysis
      of the trio-based exomes found 13 de novo variants. However, no two patients had
      de novo variants in the same gene, and additional patient exomes and mutation
      analysis in the replication cohort did not provide strong genetic evidence to
      implicate any of these sequence variants in ROHHAD. Somatic comparisons revealed
      no coding differences between any blood and tumour samples, or between the two
      discordant MZ twins. Neither autosomal dominant nor recessive analysis yielded
      candidate genes for ROHHAD, and we did not identify any potentially causative
      structural variations. CONCLUSIONS: Clinical exome sequencing is highly unlikely
      to be a useful diagnostic test in patients with true ROHHAD. As ROHHAD has a high
      risk for fatality if not properly managed, it remains imperative to expand the
      search for non-exomic genetic risk factors, as well as to investigate other
      possible mechanisms of disease. In so doing, we will be able to confirm
      objectively the ROHHAD diagnosis and to contribute to our understanding of
      obesity, respiratory control, hypothalamic function, and autonomic regulation.

PMID- 26302958
TI  - Who Let the Dogs Out? Communicating First Nations Perspectives on a Canine
      Veterinary Intervention Through Digital Storytelling.
AB  - Dog-related human injuries affect public safety and animal welfare, and occur
      more frequently in rural, remote, and Indigenous communities than in urban
      centres in Canada. Little work has been done to identify the perspectives of
      those people most heavily affected by this issue or to report successful dog
      management programs. This project was undertaken by veterinarians and public
      health workers with the goal of documenting First Nations perspectives on dogs,
      and educating other rural health workers about introducing animal management
      services to Indigenous communities. We recruited 10-14 residents and healthcare
      workers from three First Nations to take dog-related photos in their communities
      and participate in group interviews during the summer of 2014. Audiovisual data
      were synthesised into four digital stories exploring the following aspects of
      participant relationships with community dogs: (1) Spay/neuter clinics; (2) Role
      of the dog (past and present); (3) Human-animal bond; and (4) Healthy dogs as a
      part of healthy communities. These videos document changes in dog husbandry
      behaviour, new acceptance of spay/neuter, three-way knowledge transfer between
      residents, researchers, and policy makers, and an overall desire to sustain the
      positive outcomes of the pilot dog management project. This work highlights
      cultural beliefs and success strategies that might guide other programs providing
      veterinary services in First Nations communities.

PMID- 26302959
TI  - Contact to Non-human Primates and Risk Factors for Zoonotic Disease Emergence in
      the Tai Region, Cote d'Ivoire.
AB  - Elevated exposure levels to non-human primates (NHP) and NHP bushmeat represent
      major risk factors for zoonotic disease transmission in sub-Saharan Africa.
      Demography can affect personal nutritional behavior, and thus rates of contact to
      NHP bushmeat. Here, we analyzed demographic and NHP contact data from 504
      participants of differing demographic backgrounds living in proximity to the Tai
      National Park in Western Cote d'Ivoire (CI) to identify factors impacting the
      risk of NHP exposure. Overall, participants' contact rates to NHP were high, and
      increased along a gradient of bushmeat processing (e.g., 7.7% hunted, but 61.9%
      consumed monkeys). Contact to monkeys was significantly more frequent than to
      chimpanzees, most likely a reflection of meat availability and hunting effort.
      17.2% of participants reported previous interaction with NHP pets. Generalized
      linear mixed model analysis revealed significant effects of sex, country of birth
      or ethnicity on rates of NHP bushmeat contact, with male participants from CI
      being at particular risk of exposure to NHP. The presence of zoonotic pathogens
      in humans and NHP in Tai further highlights the risk for zoonotic disease
      emergence in this region. Our results are relevant for formulating prevention
      strategies to reduce zoonotic pathogen burden in tropical Africa.

PMID- 26302960
TI  - Enrichment and determination of octylphenol and nonylphenol in environmental
      water samples by solid-phase microextraction with carboxylated carbon nano
      spheres coating prior to gas chromatography-mass spectrometry.
AB  - In this paper, a novel and simple method for the sensitive determination of
      endocrine disrupter compounds octylphenol (OP) and nonylphenol (NP) in
      environmental water samples has been developed using solid-phase microextraction
      (SPME) coupled with gas chromatography-mass spectrometry. Carboxylated carbon
      nano-spheres (CNSs-COOH) are used as a novel SPME coating via physical adhesion.
      The CNSs-COOH fiber possessed higher adsorption efficiency than 100 MUm
      polydimethysiloxane (PDMS) fiber and was similar to 85 MUm polyacrylate (PA)
      fiber for the two analytes. Important parameters, such as extraction time, pH,
      agitation speed, ionic strength, and desorption temperature and time, were
      investigated and optimized in detail. Under the optimal parameters, the developed
      method achieved low limits of detection of 0.13~0.14 ng.L(-1) and a wide linear
      range of 1~1000 ng.(-1) for OP and NP. The novel method was validated with
      several real environmental water samples, and satisfactory results were obtained.

PMID- 26302961
TI  - Achieving comparability with IFCC reference method for the measurement of
      hemoglobin A1c by use of an improved isotope-dilution mass spectrometry method.
AB  - The development of reference measurement methods for hemoglobin A1c (HbA1c) is
      important for quality assurance in diabetes management. The IFCC reference method
      using purified proteins as calibration standards is the recommended accuracy
      based reference method for the standardization of HbA1c measurement. We developed
      a highly precise and accurate liquid chromatography-isotope-dilution tandem mass
      spectrometry (LC-IDMS/MS) procedure, which can serve as an alternative accuracy
      based method for HbA1c measurement. In this method, enzymatic proteolysis was
      applied to sample preparation, followed by LC-IDMS/MS measurement of hemoglobin
      A0 (HbA0) and HbA1c, using two "signature" hexapeptides for calibration. The
      concentrations of the signature hexapeptide calibration solutions were, in turn,
      determined using a hydrolysis method with HCl, followed by LC-IDMS/MS measurement
      using amino acid solutions as calibration standards. These solutions were
      gravimetrically prepared from pure amino acid certified reference materials
      (CRMs). The developed LC-IDMS/MS method was used in participation in an IFCC ring
      trial for reference laboratories (RELA 2013 and 2014) for HbA1c, where our
      results were compared with those using the IFCC reference method. The deviations
      were found to be 0.4-1.7 mmol mol(-1) [or 0.04-0.16% in National Glygohemoglobin
      Standardization Program (NGSP) units], revealing good comparability with the IFCC
      reference method. The relative expanded uncertainty of the LC-IDMS/MS was in the
      range of 2.6% to 2.8% (1.6% to 2.2% after converting to NGSP units). With
      excellent method precision, good comparability with the IFCC reference method,
      and a small measurement uncertainty, the developed LC-IDMS/MS method may be used
      as an alternative accuracy-based reference method for HbA1c measurement.

PMID- 26302962
TI  - Understanding the regioselective hydrolysis of ginkgolide B under physiological
      environment based on generation, detection, identification, and semi
      quantification of the hydrolyzed products.
AB  - A liquid chromatography-mass spectrometry (LC-MS) method coupled with specialized
      sample-preparation strategies was developed to investigate the hydrolysis of
      ginkgolide B (GB) in physiological environments in comparison with that of
      ginkgolide A (GA). The rapid hydrolysis processes were captured by the direct
      injection of samples prepared in the volatile buffers. The LC-MS behavior of the
      hydrolyzed products, including three monocarboxylates and three dicarboxylates,
      was acquired. The monocarboxylates were identified by fragmentation analysis, and
      the dicarboxylates were accordingly tentatively identified by reaction sequences.
      The base-catalyzed hydrolysis of GB and GA was characterized at 4  degrees C
      within pH 7.0-10.7. The regioselective reactions on the lactone-C and lactone-F
      were revealed by thermodynamic studies at pH 6.8 and 7.4. It was revealed that
      the 1-hydroxyl group on the skeleton of GB blocks the reactivity of the lactone
      E. On the basis of these results, a distinctive hydrolysis phenomenon of GB was
      confirmed in plasma of humans, rats, and dogs as a rapid degradation of the
      trilactone along with the only production of the lactone-F-hydrolyzed product.
      This phenomenon is also closely associated with the 1-hydroxyl group, because it
      was not observed in GA. More interestingly, the underlying mechanism was revealed
      not to be associated with any typical enzyme-catalyzed process, but to be
      potentially involved with a selective reaction of the intact or broken lactone-C
      moiety with endogenous small-molecule reactants in plasma. This in-depth
      knowledge of the hydrolysis of GB versus GA not only facilitated understanding of
      their pharmacological mechanisms but also provided potential routes to study the
      structure-activity relationships of ginkgolides. Graphical Abstract
      Regioselective hydrolysis of ginkgolide B in pH 7.4 buffers and plasma. 

PMID- 26302963
TI  - Development of a method for the analysis of hormones and pharmaceuticals in
      earthworms by quick, easy, cheap, effective, rugged and safe (QuEChERS)
      extraction followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
AB  - The earthworm represents a kind of creature in contact with the soil surface and
      usually exposed to a variety of organic pollutants from human activities.
      Therefore, it can be considered as an organism of choice for identifying
      pollution or better understanding the input of contaminants in food chains in
      particular through the contributions of sludge. Moreover, the use of organisms
      such as soil invertebrates is to be developed for ecotoxicological risk
      assessment of pollutants. In this context, a simple, rapid and effective multi
      residue method was developed for the determination of 31 compounds including 11
      steroids, 14 veterinary antibiotics and 6 human contaminants (paracetamol,
      sulfamethoxazole, fluvoxamine, carbamazepine, ibuprofen, bisphenol A) in
      earthworm. The sample preparation procedure was based on a salting-out extraction
      with acetonitrile (QuEChERS approach) that was optimised with regard to the
      acetonitrile/water ratio used in the extraction step, the choice of the clean-up
      and the quantity of the matrix. The optimised extraction method exhibited
      recoveries that comprised between 44 and 98 % for all the tested compounds. The
      limits of detection of all compounds were below 14 ng g(-1) and the limits of
      quantification (LOQ) comprised between 1.6 and 40 ng g(-1) (wet weight). The
      method was therefore applied to determine the levels of pharmaceuticals and
      hormones in six earthworm samples collected in various soils. Concentrations up
      to 195 ng g(-1) for bisphenol A were determined, between a few nanograms per gram
      and 43.1 ng g(-1) (estriol) for hormones and between a few nanograms per gram and
      73.5 ng g(-1) (florfenicol) for pharmaceuticals. Experiments were also conducted
      in laboratory conditions to evaluate the accumulation of the target substances by
      earthworm. 

PMID- 26302965
TI  - Preparation of molecularly imprinted polymer coated quantum dots to detect
      nicosulfuron in water samples.
AB  - A novel dual-function material was synthesized by anchoring a molecularly
      imprinted polymer (MIP) layer on Mn-doped ZnS quantum dots (QDs) via a sol-gel
      process using 3-aminopropyltriethoxysilane (APTES) as a functional monomer,
      tetraethoxysilane (TEOS) as cross-linker, and nicosulfuron as template through a
      surface imprinting method. The amino groups in the APTES interact with the
      functional groups in the template molecules to form a complex through hydrogen
      bonding. The energy of the QDs was transferred to the complex, resulting in the
      quenching of the QDs and thus decreasing the fluorescence intensity, which
      allowed the nicosulfuron to be sensed optically. Fluorescence intensity from MIP
      coated QDs was more strongly quenched by nicosulfuron than that of the non
      imprinted polymer, which indicated that the MIP-coated QDs which acted as a
      fluorescence probe could selectively recognize nicosulfuron. Under the optimal
      conditions, it can detect down to 1.1 nmol L(-1) of nicosulfuron, and a linear
      relationship has been obtained covering the concentration range of 12-6000 nmol
      L(-1). The recoveries were in the range from 89.6 to 96.5 %, and the relative
      standard deviations were in the range of 2.5-5.7 %. The present study established
      a new strategy to combine inorganic (Mn-doped ZnS QDs)-organic MIPs, which is
      successfully applied to determine nicosulfuron in water samples. 

PMID- 26302964
TI  - Identification of chemical markers in Cordyceps sinensis by HPLC-MS/MS.
AB  - Authentication and quality assessment of Cordyceps sinensis, a precious and
      pricey natural product that offers a variety of health benefits, is highly
      significant. To identify effective chemical markers, authentic C. sinensis was
      thoroughly screened by using HPLC-MS/MS. In addition to many previously reported
      ingredients, two glycosides, i.e., cyclo-Ala-Leu-rhamnose and Phe-o-glucose, were
      detected for the first time in this material. Six ingredients detected, including
      cordycepin, D-mannitol, Phe, Phe-o-glucose, cyclo-Gly-Pro, and cyclo-Ala-Leu
      rhamnose, were selected as a collection of chemical markers. An HPLC-MS/MS method
      was developed to simultaneously quantify them with sensitivity and specificity.
      The method had limits of detection ranging from 0.008 MUg mL(-1) for cordycepin
      to 0.75 MUg mL(-1) for cyclo-Gly-Pro. Recovery was found between 96 and 103 % in
      all tests. To evaluate the effectiveness of the marker collection proposed, five
      authentic C. sinensis samples and five samples of its substitutes were analyzed.
      Cordycepin, D-mannitol, and Phe were found present in all samples. The contents
      ranged from 0.0076 to 0.029 % (w/w) for cordycepin, 0.33 to 18.9 % for mannitol,
      and 0.0013 to 0.642 % for Phe. Interestingly, the two glycosides, Phe-o-glucose
      and cyclo-Ala-Leu-rhamnose, were detected only in authentic C. sinensis samples.
      These results indicated that the proposed protocol based on HPLC-MS/MS
      quantification of the markers might have a great potential in authentication and
      quality assessment of C. sinensis. Graphical abstract Chemical markers of C.
      sinensis identified in this work. 

PMID- 26302966
TI  - Two-dimensional covalent triazine framework as an ultrathin-film nanoporous
      membrane for desalination.
AB  - We computationally demonstrate that two-dimensional covalent triazine frameworks
      (CTFs) provide opportunities in water desalination. By varying the chemical
      building blocks, the pore structure, chemistry, and membrane performance can be
      designed, leading to two orders of magnitude higher water permeability than
      polyamide membranes while maintaining excellent ability to reject salts. 

PMID- 26302967
TI  - Preparation, characterization and in vitro-targeted delivery of novel
      Apolipoprotein E-based nanoparticles to C6 glioma with controlled size and
      loading efficiency.
AB  - Apolipoprotein E (APOE) with its extraordinary features is readily assembled with
      hydrophobic compounds via its compact hydrophobic units (CHUs). These assemblies
      can then be converted to stable particles by protein-protein interactions via
      coiled coil regions (CCRs) which exist in APOE structure. Applying these features
      of APOE, we prepared novel nanoparticles called NAPOE, using no cross-linker.
      Vitamin D3 - a hydrophobic antitumor model - was loaded within the nanoparticles
      (NPs). The NPs were mostly spherical with the mean diameter and zeta potential of
      94.39 +/- 5.71 nm and -20 +/- 0.3 mV, respectively. The molar ratio of VD3/APOE
      in NPs was 37.2 +/- 0.61. The NPs targeted C6 glioma cells in vitro via over
      expressed LDLRs. The efficiency of the NPs uptake to malignant C6 glioma cells
      was remarkable compared to non-tumor glial cells (p < 0.05). The releasing rate
      of hydrophobic cargo from the particles was high (p < 0.05) and reached to
      maximum, 12 h after targeting C6 cells. The size and drug loading of NPs were
      found to be controlled by the definite numbers of CCRs and CHUs in APOE. In
      conclusion, it is suggested that NAPOE NPs can facilitate the controlled delivery
      of hydrophobic drugs to the malignant C6 glioma cells according to the degree of
      invasiveness. 

PMID- 26302968
TI  - Universal pattern transfer methods for metal nanostructures by block copolymer
      lithography.
AB  - A universal block copolymer pattern transfer method was demonstrated to produce
      Co nanostructures consisting of arrays of lines or dots from a polystyrene-block
      polydimethylsiloxane (PS-b-PDMS) diblock copolymer. Three processes were used:
      liftoff, a damascene process, and ion beam etching using a hard mask of tungsten,
      including a sacrificial poly(methyl methacrylate) layer under the PS-b-PDMS for
      the etch and liftoff processes. The ion beam etch process produced the most
      uniform magnetic arrays. A structural and magnetic comparison in terms of
      uniformity, edge roughness and switching field distribution has been reported. 

PMID- 26302969
TI  - Significance of the Splenic Vein and Its Branches in Pancreatoduodenectomy with
      Resection of the Portal Vein System.
AB  - BACKGROUND/AIMS: Pancreatic head carcinoma frequently invades the superior
      mesenteric vein (SMV) and/or portal vein (PV). We aimed to evaluate the outcome
      of transection of the splenic vein (SV) and inferior mesenteric vein (IMV) in
      pancreatoduodenectomy (PD) with SMV and/or PV resection. METHODS: We
      retrospectively analyzed the records of 660 patients who had undergone
      pancreatectomy at our institution from January 2004 to October 2013, and selected
      141 consecutive patients who had undergone PD with concurrent SMV/PV resection.
      Postoperative hypersplenism and the presence of remnant branches were evaluated.
      RESULTS: The SV had been transected in 81 patients and preserved in 60.
      Postoperative complications and white blood cell counts were similar between the
      groups. The postoperative splenic volume was not significantly associated with
      the status of the SV or IMV on the transected SV. The platelet count was
      significantly lower, and the incidence of collateral veins was higher after SV
      transection than after SV preservation until 6 months after surgery; these
      variables were similar in the long term. CONCLUSION: SV reconstruction might be
      unnecessary when SV transection is required. Preservation of the IMV on the
      remnant SV might not prevent sinistral portal hypertension.

PMID- 26302970
TI  - Giant Cell Tumor of the Patella Tendon Sheath Presenting as a Painful Locked
      Knee.
AB  - BACKGROUND: The giant cell tumor of the tendon sheath (GCT-TS) is a benign
      proliferative synovial tumor manifesting as an intra-articular solitary nodule.
      When it involves the infrapatellar fat pad it can present acutely as a painful
      locked knee. CASE REPORT: A 26-year-old white male presented with a 2-week
      history of painful locking in his right knee. Clinical examination revealed lack
      of extension by approximately 20 degrees . To help establish the diagnosis, an
      MRI scan of the right knee was performed, showing a large (5*4*2 cm), oval, well
      circumscribed mass with a low-intensity homogenous signal. The size of the mass
      prohibited the removal by arthroscopy and we therefore proceeded with an open
      arthrotomy. Histological examination showed a tendosynovial giant cell tumor of
      the patella tendon sheath. At the latest follow-up, 2 years postoperatively,
      there was no local tumor recurrence. CONCLUSIONS: These rare tumorous lesions
      should be included in the differential diagnosis of painful locking knee,
      especially in the absence of definite traumatic history.

PMID- 26302971
TI  - Interleukin-18, interleukin-12B and interferon-gamma gene polymorphisms in
      Brazilian patients with rheumatoid arthritis: a pilot study.
AB  - Polymorphisms in interleukin (IL)-18, IL-12 and interferon (IFN)-gamma genes are
      associated with different levels of cytokines expression and have been associated
      with rheumatoid arthritis (RA). IL-18 +105 A/C, IL-12B +1188 A/C and IFN-gamma
      +874 T/A polymorphisms were analyzed by restriction fragment length polymorphism
      polymerase chain reaction (PCR) and amplification refractory mutation system PCR
      from 90 RA patients and 186 healthy individuals. There were significant
      differences to IL-18 +105 A/C polymorphism between the RA and control groups
      (odds ratio = 3.77; P < 0.0001). Individual carriers of the variant allele C had
      a 3.77-fold increased risk of for RA (P = 0.0032). No association was observed
      for IL-12B and IFN-gamma polymorphisms. Our finds suggest a possible role for IL
      18 polymorphism in the RA susceptibility in studied population.

PMID- 26302972
TI  - Videodermatoscopy-assisted Mohs micrographic surgery vs. other treatments for
      lentigo maligna in 54 patients with a long-term follow-up.

PMID- 26302973
TI  - Intrapartum fetal surveillance.

PMID- 26302974
TI  - Leading the Way in Health Disparities Research.

PMID- 26302975
TI  - COX6A1 mutation causes axonal hereditary motor and sensory neuropathy - the
      confirmation of the primary report.

PMID- 26302976
TI  - Intraoperative blood loss is not a predictor of prognosis for pancreatic cancer.
AB  - PURPOSE: The relationship between intraoperative blood loss (IBL) and prognosis
      has been reported for some types of cancer, but not for pancreatic cancer, which
      has one of the highest mortality rates of any cancer. We conducted this study to
      analyze the relationship between IBL and clinical outcome for patients undergoing
      radical surgery for pancreatic cancer. METHODS: The subjects of this study were
      144 patients who underwent curative pancreatectomy for invasive pancreatic cancer
      between 2002 and 2014. Clinicopathological characteristics were recorded and
      prognostic factors were identified by univariate and multivariate analyses.
      RESULTS: Large IBL was significantly associated with advanced tumor stage, a long
      operation time, a large tumor, portal vein resection, and blood transfusion.
      According to univariate analysis, IBL was also significantly associated with
      overall survival (OS) and relapse-free survival (RFS); however, it was not an
      independent prognostic factor for OS and RFS in multivariate analysis. According
      to multivariate analysis, lymph node metastasis and R-status were independent
      prognostic factors for OS and RFS. A subgroup analysis of patients who received
      no blood transfusion showed similar results. CONCLUSION: Minimizing IBL is very
      important; however, the present study found that positive lymph node metastasis
      and R-status were stronger independent prognostic factors for pancreatic cancer.

PMID- 26302977
TI  - Expression of steroidogenesis-related genes in murine male germ cells.
AB  - For decades, only few tissues and cell types were defined as steroidogenic,
      capable of de novo steroid synthesis from cholesterol. However, with the
      refinement of detection methods, several tissues have now been added to the list
      of steroidogenic tissues. Besides their critical role as long-range acting
      hormones, steroids are also playing more discreet roles as local mediators and
      signaling molecules within the tissues they are produced. In testis,
      steroidogenesis is carried out by the Leydig cells through a broad network of
      proteins, mediating cholesterol delivery to CYP11A1, the first cytochrome of the
      steroidogenic cascade, and the sequential action of enzymes insuring the
      production of active steroids, the main one being testosterone. The knowledge
      that male germ cells can be directly regulated by steroids and that they express
      several steroidogenesis-related proteins led us to hypothesize that germ cells
      could produce steroids, acting as autocrine, intracrine and juxtacrine
      modulators, as a way to insure synchronized progression within spermatogenic
      cycles, and preventing inappropriate cell behaviors between neighboring cells.
      Gene expression and protein analyses of mouse and rat germ cells from neonatal
      gonocytes to spermatozoa showed that most steroidogenesis-associated genes are
      expressed in germ cells, showing cell type-, spermatogenic cycle-, and age
      specific expression profiles. Highly expressed genes included genes involved in
      steroidogenesis and other cell functions, such as Acbd1 and 3, Tspo and Vdac1-3,
      and genes involved in fatty acids metabolism or synthesis, including Hsb17b4 10
      and 12, implying broader roles than steroid synthesis in germ cells. These
      results support the possibility of an additional level of regulation of
      spermatogenesis exerted between adjacent germ cells. 

PMID- 26302978
TI  - Effect of time of progesterone supplementation on serum progesterone and the
      conception rate of cooled Holstein heifers during the summer.
AB  - To investigate the effects of progesterone supplementation at two different times
      on serum progesterone (P4 ) concentration, conception rate and resynchronization
      of cooled Holstein heifers in summer, 90 heifers were randomly assigned to two
      groups: (i) heifers subjected to TAI (timed artificial insemination) and
      progesterone supplementation from days 4 to 14 after TAI (S1; n = 45); and (ii)
      heifers under the same TAI protocol as S1 and progesterone supplementation from
      days 17 to 22 after TAI (S2 ; n = 45). The groups S1 and S2 were cooled 10 days
      before and 21 days after TAI. Respiratory rate, body surface temperature, vaginal
      temperature and rectal temperature recorded during the experiment were not
      different (P > 0.05) between S1 and S2 groups. Progesterone concentration was not
      different (P > 0.05) in S1 compared to S2 . The conception rates on days 30 and
      55 were similar between groups (P > 0.05). Progesterone supplementation did not
      increase either conception rate or concentrations of P4 in heifers during the
      summer. Heifers not pregnant to first service in the group S2 were resynchronized
      (77.7%) for a second breeding. 

PMID- 26302979
TI  - Higher Leptin and Adiponectin Concentrations Predict Poorer Performance-based
      Physical Functioning in Midlife Women: the Michigan Study of Women's Health
      Across the Nation.
AB  - BACKGROUND: Excess fat mass is a greater contributor to functional limitations
      than is reduced lean mass or the presence of obesity-related conditions. The
      impact of fat mass on physical functioning may be due to adipokines, adipose
      derived proteins that have pro- or anti-inflammatory properties. METHODS: Serum
      samples from 1996 to 2003 that were assayed for leptin, adiponectin, and resistin
      were provided by 511 participants from the Michigan site of the Study of Women's
      Health Across the Nation. Physical functioning performance was assessed annually
      during study visits from 1996 to 2003. RESULTS: Among this population of Black
      and White women (mean baseline age = 45.6 years, SD = 2.7 years), all of whom
      were premenopausal at baseline, higher baseline leptin concentrations predicted
      longer stair climb, sit-to-rise, and 2-pound lift times and shorter forward reach
      distance (all p < .01). This relationship persisted after adjustment for age,
      BMI, percent skeletal muscle mass, race/ethnicity, economic strain, bodily pain,
      diabetes, knee osteoarthritis, and C-reactive protein. Baseline total adiponectin
      concentrations did not predict any mobility measures but did predict quadriceps
      strength; a 1 ug/mL higher adiponectin concentration was associated with 0.64 Nm
      lower quadriceps strength (p = .02). Resistin was not associated with any of the
      physical functioning performance measures. Change in the adipokines was not
      associated with physical functioning. CONCLUSION: In this population of middle
      aged women, higher baseline leptin concentrations predicted poorer mobility-based
      functioning, whereas higher adiponectin concentrations predicted reduced
      quadriceps strength. These findings suggest that the relationship between the
      adipokines and physical functioning performance is independent of other known
      correlates of poor functioning.

PMID- 26302981
TI  - Soluble Vascular Endothelial Growth Factor (sVEGF) and the Risk of Venous
      Thromboembolism in Patients with Cancer: Results from the Vienna Cancer and
      Thrombosis Study (CATS).
AB  - PURPOSE: Cancer patients are at an increased risk of venous thromboembolism
      (VTE). VEGF promotes the growth of highly thrombogenic tumor vessels. Here, we
      explored the utility of soluble plasma VEGF-A (sVEGF) as a biomarker for the
      prediction of VTE in patients with cancer. EXPERIMENTAL DESIGN: Eight hundred
      four patients with newly diagnosed cancer or progression after remission were
      prospectively followed for 2 years until the occurrence of VTE or death [tumor
      sites: brain (n = 87), breast (n = 137), lung (n = 120), gastrointestinal (n =
      143), pancreas (n = 53), prostate (n = 95), kidney (n = 22), myeloma and lymphoma
      (n = 99), and others (n = 48)]. Primary endpoint was symptomatic or fatal VTE.
      sVEGF was measured by immunoassay in baseline plasma. RESULTS: Fifty-five
      patients developed VTE (6.8%) and 364 patients (45.3%) died. Five-hundred and
      forty-two (68.3%) participants had sVEGF levels above the detection limit of 0.5
      pg/mL. The median sVEGF level (25th-75th percentile) was 8.1 pg/mL (0-17.7). The
      cumulative 2-year incidence of VTE was 10.2% [95% confidence interval (CI), 6.4
      14.9] in patients with sVEGF greater than the 75th percentile of the sVEGF
      distribution (Q3, cutoff: 17.7 pg/mL), and 5.9% (95% CI, 4.2-7.9) in patients
      with lower levels (P = 0.03). The corresponding 2-year risk of death was 52.8%
      (95% CI, 46.0-60.0) and 43.9% (95% CI, 40.0-48.0), respectively (P = 0.02). In
      univariable time-to-VTE regression, elevated sVEGF was associated with VTE
      [subhazard ratio (SHR) per 10 pg/mL increase, 1.04; 95% CI,1.00-1.09; P = 0.04)].
      The association between sVEGF and risk of VTE prevailed after multivariable
      adjustment for high-risk tumor sites, age, gender, factor VIII, thrombin
      generation potential, and soluble P-Selectin (adjusted SHR, 1.04; 95% CI, 1.00
      1.09, P = 0.05). CONCLUSIONS: Elevated sVEGF is associated with an increased risk
      of VTE in patients with cancer.

PMID- 26302982
TI  - "Black henna" tattoos can cause blistering and scarring, doctors warn.

PMID- 26302983
TI  - No Evidence for Unconscious Lie Detection: A Significant Difference Does Not
      Imply Accurate Classification.

PMID- 26302984
TI  - Body surface area determined by whole-body CT scanning: need for new formulae?
AB  - Calculation of the estimated body surface area (BSA) by body height and weight
      has been a challenge in the past centuries due to lack of a well-documented gold
      standard. More recently, available techniques such as 3D laser surface scanning
      and CT scanning may be expected to quantify the BSA in an easier and more
      accurate way. This study provides the first comparison between BSA obtained from
      post-mortem whole-body CT scans and BSA calculated by nine predictive formulae.
      The sample consisted of 54 male cadavers ranging from 20 to 87 years old. 3D
      reconstructions were generated from CT scans using Mimics software, and BSA
      values were automatically extracted from the program. They were compared with
      nine predictive equations from the literature. Remarkably, close correlations (r
      > 0.90) were found between BSA values from CT scans and those from the predictive
      formulae. A mean BSA of the 54 cadavers of 1.84-1.87 m2 was calculated by all
      formulae except one, SD values varying between 0.171 and 0.223 m2 . T-tests
      revealed significant differences between mean BSA values calculated with CT and
      three of the formulae. Regression analyses showed intercepts >(0;0) and slopes
      <1.0 using all predictive equations, with the CT scan determination as gold
      standard. It is concluded that DuBois and DuBois' equation can be safely used in
      normal-weight male subjects with high accuracy, but it seems likely that BSA is
      underestimated in underweight subjects and overestimated in overweight
      individuals. Creation of new formulae specific for overweight subjects and
      children may be needed.

PMID- 26302980
TI  - Phosphatidylinositolphosphate phosphatase activities and cancer.
AB  - Signaling through the phosphoinositide 3-kinase pathways mediates the actions of
      a plethora of hormones, growth factors, cytokines, and neurotransmitters upon
      their target cells following receptor occupation. Overactivation of these
      pathways has been implicated in a number of pathologies, in particular a range of
      malignancies. The tight regulation of signaling pathways necessitates the
      involvement of both stimulatory and terminating enzymes; inappropriate activation
      of a pathway can thus result from activation or inhibition of the two signaling
      arms. The focus of this review is to discuss, in detail, the activities of the
      identified families of phosphoinositide phosphatase expressed in humans, and how
      they regulate the levels of phosphoinositides implicated in promoting malignancy.

PMID- 26302985
TI  - Secondary organ fistulation after thoracic endovascular aortic repair.
AB  - This manuscript describes the mechanisms behind aorto-oesophageal fistulation
      (AOF) and aortobronchial/pulmonary (ABPF) fistulation after TEVAR, reports the
      therapeutical approaches and defines recommendations how to prevent these
      complications in the future. 

PMID- 26302986
TI  - Parasitic Wasps Aphidius ervi are More Attracted to a Blend of Host-Induced Plant
      Volatiles than to the Independent Compounds.
AB  - Arthropodal natural enemies respond to volatiles from plants infested by their
      prey/host herbivores (herbivore-induced plant volatiles; HIPVs). However, the
      relative importance of HIPV blends vs. each compound in the blend in attracting
      natural enemies is not fully understood. In this study, we investigated the
      response of a parasitic wasp, Aphidius ervi, to HIPVs that were specific or
      nonspecific to infestations by its host aphid, Acyrthosiphon pisum. To select
      such compounds, we compared the volatiles emitted from broad bean plants infested
      by either A. pisum (host) or by Aphis craccivora (nonhost), and selected the host
      specific HIPVs beta-myrcene, n-octanal, and alpha-phellandrene, and host
      nonspecific HIPVs (E)-beta-ocimene, gamma-terpinene, and linalool as test
      compounds. For each compound, we used a range that covered the amounts emitted
      from infested broad bean plants for bioassays. Female wasps preferred n-octanal
      and (E)-beta-ocimene at 10-ng and 30-ng doses over clean air. Interestingly, the
      wasps preferred alpha-phellandrene at 0.1-ng and 30-ng doses, but not at 1-ng and
      10-ng doses. The wasps repelled linalool over clean air at 1-ng and 0.1-ng doses.
      We then mixed the equivalent amounts of the six compounds to test the effect of
      the blend. The wasps responded to a blend of six HIPV components at all
      concentrations tested (0.001 ng each to 5 ng each). These results suggested that
      the blend provided more useful information for female wasps than the individual
      compounds. The possible use of the single component and the blend for the
      biological control of A. ervi is discussed. 

PMID- 26302987
TI  - Fungal Symbionts of the Spruce Bark Beetle Synthesize the Beetle Aggregation
      Pheromone 2-Methyl-3-buten-2-ol.
AB  - Tree-killing bark beetles depend on aggregation pheromones to mass-attack their
      host trees and overwhelm their resistance. The beetles are always associated with
      phytopathogenic ophiostomatoid fungi that probably assist in breaking down tree
      resistance, but little is known about if or how much these fungal symbionts
      contribute to the beetles' aggregation behavior. In this study, we determined the
      ability of four major fungal symbionts of the spruce bark beetle Ips typographus
      to produce beetle aggregation pheromones. The fungi were incubated on Norway
      spruce Picea abies bark, malt agar, or malt agar amended with 0.5% (13)C glucose.
      Volatiles present in the headspace of each fungus were analyzed for 7 days after
      incubation using a SPME autosampler coupled to a GC/MS. Two Grosmannia species
      (G. penicillata and G. europhioides) produced large amounts of 2-methyl-3-buten-2
      ol (MB), the major component in the beetles' aggregation pheromone blend, when
      growing on spruce bark or malt agar. Grosmannia europhioides also incorporated
      (13)C glucose into MB, demonstrating that the fungi can synthesize MB de novo
      using glucose as a carbon source. This is the first clear evidence that fungal
      symbionts of bark beetles can produce components in the aggregation pheromone
      blend of their beetle vectors. This provides new insight into the possible
      ecological roles of fungal symbionts in bark beetle systems and may deepen our
      understanding of species interactions and coevolution in these important
      biological systems.

PMID- 26302989
TI  - Trauma in children due to wheeled recreational devices.
AB  - AIM: The aim of this study was to describe trauma in children secondary to the
      use of wheeled recreational devices (WRDs). METHODS: This study retrospectively
      described trauma secondary to use of WRDs sustained by children 16 years or
      younger over a period of 12 months at two tertiary paediatric hospitals in
      Brisbane, Queensland. Data were analysed from the Paediatric Trauma Registry at
      these two facilities. Data were also retrieved from The Commission for Children
      and Young People and Child Guardian to provide information regarding deaths in
      Queensland from the use of WRDs for the period January 2004 to September 2013.
      Outcome measures included age, gender, types of injuries, Injury Severity Scores,
      admission to Intensive Care, and length of hospital stay for all hospital
      admissions greater than 24 h. RESULTS: A total number of 45 children were
      admitted with trauma relating to WRDs during the 12 months, representing 5.3% of
      all trauma admissions of greater than 24 h during this time period. Of these, 34
      were male with a median age of 11.0 years (IQR = 9-13). Limbs accounted for the
      majority (54.5%) of injuries, with other common injuries being spine/cranial
      fractures (14.5%), lacerations (12.7%), internal organ injuries (9.1%), and
      intracranial bleeds (9.1%). There were six admissions to the Paediatric Intensive
      Care Unit and one death. CONCLUSIONS: WRDs contribute significantly to injuries
      sustained by children. A large proportion of these injuries may be preventable,
      suggesting that mandating the use of protective equipment in Queensland may be of
      great benefit.

PMID- 26302988
TI  - Psychosocial well-being of parents of children with oral clefts.
AB  - BACKGROUND: Parents of children with oral clefts may be impacted psychosocially
      in several ways, but empirical evidence remains relatively sparse. The aim of
      this study was to identify predictors of psychosocial well-being of parents of
      affected children. METHODS: The study included a total sample of 287 parents (171
      mothers and 116 fathers) of children with oral clefts. Parents completed
      validated psychosocial instruments to measure social avoidance and distress, fear
      of negative evaluation scale, self-esteem and interpersonal support. Regression
      analysis was used to evaluate how selected child, parent and household
      characteristics relate to psychosocial outcomes focusing on child's cleft type,
      sex and age, differences between mothers and fathers, marital status and
      household income. RESULTS: Fathers had higher self-esteem than mothers (P = 0.01)
      and lower concern of being negatively judged by others (P < 0.0001) but also had
      lower perception of having someone to talk to about their problems (P = 0.01).
      High household income was associated with greater self-esteem and perception of
      social support (<0.05). Parents of male affected children had greater perception
      of social support than parents of female affected children (P = 0.04). No
      significant differences in parental psychosocial status measures were found by
      cleft type. Similarly, there is little evidence of changes with child age, except
      for an increase in parental distress and decline in self-esteem during mid
      adolescence (age 15-17 years). CONCLUSIONS: The results indicate that mothers and
      fathers of children with oral clefts may differ in their psychosocial adjustment
      and that mothers may overall experience more psychosocial problems than fathers.
      Also, parents from less wealthy households may be at greater risk. Parental
      psychosocial status should be considered in holistic family-based treatment
      approaches to reduce burden on affected families and improve their well-being.

PMID- 26302990
TI  - Automated Cerebrospinal Fluid Cell Counts Using the New Body Fluid Mode of Sysmex
      UF-1000i.
AB  - BACKGROUND: We evaluated the new body fluid module on Sysmex UF1000-i (UF1000i
      BF) for analysis of white blood cell (WBC) and red blood cell (RBC) in
      cerebrospinal fluid (CSF). METHODS: WBC and RBC counting were compared between
      UF1000i-BF and Fuchs-Rosenthal counting chamber in 67 CSF samples. This study
      also included the evaluation of between-day precision, limit of blank (LoB),
      limit of detection (LoD), functional sensitivity (limit of quantitation, LoQ),
      carryover and linearity. Diagnostic agreement for differentiation between normal
      and increased WBC counts (>=5.0 * 10(6) /L) was also assessed. RESULTS: The
      agreement between UF1000i-BF and manual WBC counts was otpiaml in all CSF samples
      (r = 0.99; y = 1.05x + 0.09). A modest overestimation was noticed in samples with
      WBC < 30 * 10(6) /L (r = 0.95; y = 1.21x - 0.15). A good agreement was observed
      for RBC counts (r = 0.98; y = 1.15x + 0.55), particularly in samples with RBC >=
      18 * 10(6) /L (r = 0.98; y = 1.01x + 8.90). Between-day precision was good, with
      coefficient of variations (CVs) lower than 7.2% for both WBC and RBC. The LoBs
      were 0.1 * 10(6) WBC/L and 1.2 * 10(6) RBC/L, the LoDs were 0.7 * 10(6) WBC/L and
      5.5 * 10(6) RBC/L, the LoQs were 2.4 * 10(6) WBC/L and 18.0 * 10(6) RBC/L,
      respectively. Linearity was excellent (r = 1.00 for both WBC and RBC). Carryover
      was negligible. Excellent diagnostic agreement was obtained at 4.5 * 10(6) WBC/L
      cut-off (sensitivity, 100%; specificity, 97.4%). CONCLUSION: The UF1000i-BF
      provides rapid and accurate WBC and RBC counts in clinically relevant values of
      CSF cells. The use of UF1000i-BF may hence allow to replace routine optical
      counting, except for samples displaying abnormal WBC counts or abnormal
      scattergram distribution, for which differential cell counts may still be
      required.

PMID- 26302992
TI  - How Many Biochemistries Are Available To Build a Cell?
AB  - The manual experimental evolution of the bacterium Escherichia coli allowed the
      design of a noncanonical genetic code in which complete replacement of the
      endogenous building block tryptophan (left) by an exogenous one based on a
      thienylpyrrole (right) was achieved after 506 days of continuous culturing. 

PMID- 26302991
TI  - Epigenetically Enhanced Photodynamic Therapy (ePDT) is Superior to Conventional
      Photodynamic Therapy for Inducing Apoptosis in Cutaneous T-Cell Lymphoma.
AB  - Conventional photodynamic therapy with aminolevulinate (ALA-PDT) selectively
      induces apoptosis in diseased cells and is highly effective for treating actinic
      keratoses. However, similar results are achieved only in a subset of patients
      with cutaneous T-cell lymphoma (CTCL). Our previous work shows that the apoptotic
      resistance of CTCL correlates with low expression of death receptors like Fas
      cell surface death receptor (FAS), and that methotrexate upregulates FAS by
      inhibiting the methylation of its promoter, acting as an epigenetic derepressor
      that restores the susceptibility of FAS-low CTCL to caspase-8-mediated apoptosis.
      Here, we demonstrate that methotrexate increases the response of CTCL to ALA-PDT,
      a concept we refer to as epigenetically enhanced PDT (ePDT). Multiple CTCL cell
      lines were subjected to conventional PDT versus ePDT. Apoptotic biomarkers were
      analyzed in situ with multispectral imaging analysis of immunostained cells, a
      method that is quantitative and 5* more sensitive than standard immunohistology
      for antigen detection. Compared to conventional PDT or methotrexate alone, ePDT
      led to significantly greater cell death in all CTCL cell lines tested by inducing
      greater activation of caspase-8-mediated extrinsic apoptosis. Upregulation of FAS
      and/or tumor necrosis factor-related apoptosis-inducing ligand pathway components
      was observed in different CTCL cell lines. These findings provide a rationale for
      clinical trials of ePDT for CTCL.

PMID- 26302994
TI  - Circulatory support devices: fundamental aspects and clinical management of
      bleeding and thrombosis.
AB  - Circulatory support devices are increasingly being used to overcome cardiac or
      respiratory failure. Long-term devices are used either as a 'bridge to
      transplant' to support patients who are unable to wait any longer for a heart
      transplant, or, more recently, as 'destination therapy' for older patients
      suffering from end-stage heart failure and who have contraindications to heart
      transplantation. Short-term support devices for high-risk percutaneous coronary
      intervention, or as a 'bridge for decision' for patients suffering from
      refractory cardiogenic shock, have also been developed. The clinical benefit of
      such assist devices has been demonstrated in several important studies, but,
      unfortunately, thrombotic and bleeding complications are two major clinical
      issues in patients requiring these devices. Overcoming these issues is of major
      importance to allow the safe and broad use of these devices, and to consider them
      as true alternatives to heart transplantation. The present review focuses on
      thrombotic and bleeding complications, and describes how the risk of thrombosis
      and bleeding may vary according to the clinical indication, but also according to
      the type of device. We describe the current knowledge of the mechanisms
      underlying the occurrence of these complications, provide some guidance for
      choosing the most appropriate anticoagulation regimen to prevent their occurrence
      for each type of device and indication, and provide some recommendations for the
      management of patients when the complication occurs. 

PMID- 26302995
TI  - The Innate Immune Receptor CD14 Mediates Lymphocyte Migration in EAE.
AB  - BACKGROUND: Multiple sclerosis is the most common autoimmune disease of the
      central nervous system in young adults and histopathologically characterized by
      inflammation, demyelination and gliosis. It is considered as a CD4+ T cell
      mediated disease, but also a disease-promoting role of the innate immune system
      has been proposed, based e.g. on the observation that innate immune receptors
      modulate disease severity of experimental autoimmune encephalomyelitis. Recent
      studies of our group provided first evidence for a key role of the innate immune
      LPS receptor (CD14) in pathophysiology of experimental autoimmune
      encephalomyelitis. CD14-deficient experimental autoimmune encephalomyelitis mice
      showed increased clinical symptoms and enhanced infiltration of monocytes and
      neutrophils in brain and spinal cord. METHODS: In the current study, we further
      investigated the causes of the disease aggravation by CD14-deficiency and
      examined T cell activation, also focusing on the costimulatory molecules CTLA-4
      and CD28, and T cell migration capacity over the blood brain barrier by FACS
      analysis, in vitro adhesion and transmigration assays. RESULTS: In the results,
      we observed a significantly increased migration of CD14-deficient lymphocytes
      across an endothelial monolayer. In contrast, we did not see any differences in
      expression levels of TCR/CTLA-4 or TCR/CD28 and lymphocyte adhesion to
      endothelial cells from CD14-deficient compared to wildtype mice. CONCLUSION: The
      results demonstrate an important role of CD14 in migration of lymphocytes, and
      strengthen the importance of innate immune receptors in adaptive immune
      disorders, such as multiple sclerosis.

PMID- 26302997
TI  - Fast experiments for structure elucidation of small molecules: Hadamard NMR with
      multiple receivers.
AB  - We propose several significant improvements to the PANSY (Parallel NMR
      SpectroscopY) experiments-PANSY COSY and PANSY-TOCSY. The improved versions of
      these experiments provide sufficient spectral information for structure
      elucidation of small organic molecules from just two 2D experiments. The PANSY
      TOCSY-Q experiment has been modified to allow for simultaneous acquisition of
      three different types of NMR spectra-1D C-13 of non-protonated carbon sites, 2D
      TOCSY and multiplicity edited 2D HETCOR. In addition the J-filtered 2D PANSY
      gCOSY experiment records a 2D HH gCOSY spectrum in parallel with a (1) J-filtered
      HC long-range HETCOR spectrum as well as offers a simplified data processing. In
      addition to parallel acquisition, further time savings are feasible because of
      significantly smaller F1 spectral windows as compared to the indirect detection
      experiments. Use of cryoprobes and multiple receivers can significantly alleviate
      the sensitivity issues that are usually associated with the so called direct
      detection experiments. In cases where experiments are sampling limited rather
      than sensitivity limited further reduction of experiment time is achieved by
      using Hadamard encoding. In favorable cases the total recording time for the two
      PANSY experiments can be reduced to just 40 s. The proposed PANSY experiments
      provide sufficient information to allow the CMCse software package (Bruker) to
      solve structures of small organic molecules.

PMID- 26302996
TI  - Rapamycin Combined with Immature Dendritic Cells Attenuates Obliterative
      Bronchiolitis in Trachea Allograft Rats by Regulating the Balance of Regulatory
      and Effector T Cells.
AB  - BACKGROUND: Obliterative bronchiolitis (OB) ranks as the major obstacle for long
      term survival of lung transplantation patients. Rapamycin (Rapa) has recently
      been confirmed as an immunosuppressant for antirejection due to its suppressive
      role in T cell activation. Here, we explore the effect of Rapa combined with
      immature dendritic cells (imDCs) on OB in trachea allograft rats. METHODS: The
      effect of bone marrow-derived imDCs or Rapa-imDCs on lymphocyte cells and CD4+ T
      cells were evaluated by methyl thiazolyl tetrazolium and flow cytometry. Tracheal
      transplantation was performed from Lewis rats to Wistar recipients. Recipient
      rats received Rapa+imDCs for 10 consecutive days after implantation. Allograft
      rejection was assessed by micro-CT image, hematoxylin/eosinHE staining and flow
      cytometry. The underlying mechanism was also investigated. RESULTS: Rapa-imDCs
      inhibited lymphocyte and CD4+ T cell growth. Furthermore, Rapa-imDC treatment
      induced T cell hyporesponsiveness by attenuating T cell differentiation into IFN
      x03B3;-producing T cells (Th1), but increased CD4+CD25+Foxp3+ T cell (Treg)
      contents. Importantly, Rapa-imDC administration ameliorated airway obliteration
      symptoms and CD4+ and CD8+ T cell infiltration. Furthermore, the proinflammatory
      factor levels of IL-6, TNF-alpha, IFN-x03B3; and IL-17 were decreased,
      concomitant with the upregulation of immunosuppressive cytokines IL-10 and TGF
      beta1. Further analysis confirmed that Rapa-imDC treatment attenuated the amounts
      of infiltrated IL-17+CD4+ T cells (Th17 cells) and Th1 cells, but increased Treg
      contents in the spleens of recipients. CONCLUSIONS: This research may corroborate
      a protective role of Rapa-imDCs in OB by regulating the balance between effector
      T cells and Tregs, suggesting a potential applicable strategy to treat OB after
      lung transplantation.

PMID- 26302998
TI  - Fractures Related to Metabolic Bone Disease in Children with Congenital Heart
      Disease.
AB  - OBJECTIVE: Critically ill children with congenital heart disease (CHD) are at
      risk for metabolic bone disease (MBD) and bone fractures. Our objective was to
      characterize a cohort of CHD patients with fractures and describe a Fragile Bone
      Protocol (FBP) developed to reduce fractures. DESIGN/SETTING: Patients who
      developed fractures in the Cardiac Intensive Care Unit (CICU) of Boston
      Children's Hospital from 3/2008 to 6/2014 were identified via quality improvement
      and radiology databases. The FBP (initiated July 2011) systematically identifies
      patients at risk for MBD and prescribes special handling precautions. RESULTS:
      Twenty-three fractures were identified in 15 children. Median age at fracture
      identification was 6.2 months, with a median duration of hospitalization before
      fracture diagnosis of 2.7 months. Six patients (40%) had single ventricle CHD.
      Hyperparathyroidism and low 25-OH vitamin D levels were present in 77% and 40% of
      those tested, respectively. Compared with patients not diagnosed with fractures,
      fracture patients had increased exposure to possible risk factors for MBD and had
      elevated parathyroid and decreased calcitriol levels.Six patients (40%) did not
      survive to hospital discharge, compared with an overall CICU mortality rate of
      2.6% (P < .01). The fracture case rate before implementation of the FBP was 2.6
      cases/1000 admissions and was 0.7/1000 after implementation of the FBP (P = .04).
      CONCLUSIONS: Critically ill CHD patients are at risk for fractures. They
      represent a complex group who frequently has hyperparathyroidism and decreased
      calcitriol levels, and each may predispose to fractures. FBPs consisting of
      identification and careful patient handling should be considered in at-risk
      patients.

PMID- 26302999
TI  - Collagen-Derived N-Acetylated Proline-Glycine-Proline in Intervertebral Discs
      Modulates CXCR1/2 Expression and Activation in Cartilage Endplate Stem Cells to
      Induce Migration and Differentiation Toward a Pro-Inflammatory Phenotype.
AB  - The factors that regulate the migration and differentiation of cartilage endplate
      stem cells (CESCs) remain unknown. N-Acetylated proline-glycine-proline (N-Ac
      PGP) is a chemokine that is involved in inflammatory diseases. The purpose of
      this study was to detect N-Ac-PGP in degenerative intervertebral discs (IVDs) and
      to determine its roles in the migration and differentiation of CESCs. Enzyme
      linked immunosorbent assay (ELISA) and liquid chromatography-mass spectrometry
      results indicated that the levels of the proteases that generate N-Ac-PGP as well
      as N-Ac-PGP levels themselves increase with the progression of IVD degeneration.
      Immunohistochemistry and an N-Ac-PGP generation assay demonstrated that nucleus
      pulposus (NP) cells generate N-Ac-PGP from collagen. The effects of N-Ac-PGP on
      the migration and differentiation of CESCs were determined using migration
      assays, RT-PCR, immunoblot analysis, and ELISA. The results showed that the
      expression of N-Ac-PGP receptors (CXCR1 and CXCR2) in CESCs was upregulated by N
      Ac-PGP. Additionally, N-Ac-PGP induced F-actin cytoskeletal rearrangement in
      CESCs and increased CESC chemotaxis. Furthermore, N-Ac-PGP recruited chondrocytes
      and spindle-shaped cells from the cartilage endplate (CEP) into the NP in vivo.
      These spindle-shaped cells expressed CD105 and Stro-1 (mesenchymal stem cell
      markers). N-Ac-PGP induced the differentiation of CESCs toward a pro-inflammatory
      phenotype with increased production of inflammatory cytokines rather than toward
      an NP-like phenotype. Our study indicated that, in the complex microenvironment
      of a degenerative disc, N-Ac-PGP is generated by NP cells and induces the
      migration of CESCs from the CEP into the NP. N-Ac-PGP induces a pro-inflammatory
      phenotype in CESCs, and these cells promote the inflammatory response in
      degenerative discs.

PMID- 26303000
TI  - Ubiquilin2 as a novel marker for detection of urothelial carcinoma cells in
      urine.
AB  - BACKGROUND: Ubiquilin 2 (UBQLN2), an ubiquitin-related protein, is strongly
      expressed in urothelial carcinoma cells, in contrast to no or less expression in
      non-neoplastic cells; it protects cancer cells from reactive oxygen species (ROS)
      induced cytotoxicity. In this study, we investigated whether UBQLN2
      immunostaining, using liquid-based cytology sample could improve the accuracy of
      cytological urine diagnosis. METHODS: Two-hundred and forty-five urinary samples,
      including 143 negative controls and 102 urothelial carcinomas, consisting of 42
      low-grade and 60 high-grade urothelial carcinomas, were used for
      immunocytochemical analysis of UBQLN2. RESULTS: Urothelial carcinoma cells were
      positive for UBQLN2-staining, while non-neoplastic cells, including renal tubular
      cells and degenerative atypical cells, were negative. Interestingly, percentage
      of nuclear stain immunopositive for UBQLN2 was significantly higher in carcinoma
      cells with high grade/invasive phenotype than in those with low grade/noninvasive
      phenotype. UBQLN2 immunostaining had an overall sensitivity of 87.6%, specificity
      of 98.6%, positive predictive value of 97.8% and negative predictive value of
      92.8% for the detection of urothelial carcinoma. CONCLUSIONS: UBQLN2
      immunostaining is a practical test for urine cytology, even in samples with few
      cells, with slight atypia or severe degenerative changes. In addition, it allows
      prediction of tumor grade and stage by examining the cellular localization of
      UBQLN2.

PMID- 26303001
TI  - Conductance based characterization of structure and hopping site density in 2D
      molecule-nanoparticle arrays.
AB  - Composite molecule-nanoparticle hybrid systems have recently emerged as important
      materials for applications ranging from chemical sensing to nanoscale
      electronics. However, creating reproducible and repeatable composite materials
      with precise properties has remained one of the primary challenges to the
      implementation of these technologies. Understanding the sources of variation that
      dominate the assembly and transport behavior is essential for the advancement of
      nanoparticle-array based devices. In this work, we use a combination of charge
      transport measurements, electron microscopy, and optical characterization
      techniques to determine the role of morphology and structure on the charge
      transport properties of 2-dimensional monolayer arrays of molecularly-interlinked
      Au nanoparticles. Using these techniques we are able to determine the role of
      both assembly-dependent and particle-dependent defects on the conductivities of
      the films. These results demonstrate that assembly processes dominate the
      dispersion of conductance values, while nanoparticle and ligand features dictate
      the mean value of the conductance. By performing a systematic study of the
      conductance of these arrays as a function of nanoparticle size we are able to
      extract the carrier mobility for specific molecular ligands. We show that
      nanoparticle polydispersity correlates with the void density in the array, and
      that because of this correlation it is possible to accurately determine the void
      density within the array directly from conductance measurements. These results
      demonstrate that conductance-based measurements can be used to accurately and non
      destructively determine the morphological and structural properties of these
      hybrid arrays, and thus provide a characterization platform that helps move 2
      dimensional nanoparticle arrays toward robust and reproducible electronic
      systems. 

PMID- 26303002
TI  - Non-Markovian Complexity in the Quantum-to-Classical Transition.
AB  - The quantum-to-classical transition is due to environment-induced decoherence,
      and it depicts how classical dynamics emerges from quantum systems. Previously,
      the quantum-to-classical transition has mainly been described with memory-less
      (Markovian) quantum processes. Here we study the complexity of the quantum-to
      classical transition through general non-Markovian memory processes. That is, the
      influence of various reservoirs results in a given initial quantum state evolving
      into one of the following four scenarios: thermal state, thermal-like state,
      quantum steady state, or oscillating quantum nonstationary state. In the latter
      two scenarios, the system maintains partial or full quantum coherence due to the
      strong non-Markovian memory effect, so that in these cases, the quantum-to
      classical transition never occurs. This unexpected new feature provides a new
      avenue for the development of future quantum technologies because the remaining
      quantum oscillations in steady states are decoherence-free. 

PMID- 26303003
TI  - Molecular epidemiology of heteroresistant vancomycin-intermediate Staphylococcus
      aureus in Brazil.
AB  - To determine the epidemiological and molecular characteristics of 12
      Staphylococcus aureus isolates presenting heteroresistance to vancomycin in
      laboratories of two cities in Santa Catarina, southern Brazil. Epidemiological
      data, including the city of isolation, health institution, and date of isolation
      were considered, as well as the associated clinical specimen. For molecular
      characterization, we analyzed the staphylococcal cassette chromosome types, the
      erm gene presence, and the genomic diversity of isolates using pulsed-field gel
      electrophoresis. The 12 isolates of S. aureus were previously confirmed as
      heteroresistance to vancomycin using the population analysis profile-area under
      curve. Regarding genetic variability, two clones were detected: the main one
      (clone A) composed of four isolates and the clones B, with two isolates. For
      clone A, two isolates presented identical band patterns and were related to the
      same hospital, with an interval of 57 days between their isolation. The other
      isolates of this clone showed no epidemiological link between them because they
      were isolated in different hospitals and had no temporal relationship. The other
      clone showed no detectable epidemiological relationship. The heteroresistance to
      vancomycin recovered in Santa Catarina State from 2009 to 2012 had, in general,
      heterogeneous genomic patterns based on pulsed-field gel electrophoresis results,
      which is in accordance with the fact that these isolates had little or no
      epidemiological relationship among them. Due to the characteristic phenotypic
      instability and often prolonged vancomycin therapy for selection, clonal spread
      is not as common as for other resistance mechanisms disseminated through
      horizontal gene transfer. 

PMID- 26303004
TI  - Fluorescent antibody test, quantitative polymerase chain reaction pattern and
      clinical aspects of rabies virus strains isolated from main reservoirs in Brazil.
AB  - Rabies virus (RABV) isolated from different mammals seems to have unique
      characteristics that influence the outcome of infection. RABV circulates in
      nature and is maintained by reservoirs that are responsible for the persistence
      of the disease for almost 4000 years. Considering the different pattern of
      pathogenicity of RABV strains in naturally and experimentally infected animals,
      the aim of this study was to analyze the characteristics of RABV variants
      isolated from the main Brazilian reservoirs, being related to a dog (variant 2),
      Desmodus rotundus (variant 3), crab eating fox, marmoset, and Myotis spp. Viral
      replication in brain tissue of experimentally infected mouse was evaluated by two
      laboratory techniques and the results were compared to clinical evolution from
      five RABV variants. The presence of the RABV was investigated in brain samples by
      fluorescent antibody test (FAT) and real time polymerase chain reaction (qRT-PCR)
      for quantification of rabies virus nucleoprotein gene (N gene). Virus replication
      is not correlated with clinical signs and evolution. The pattern of FAT is
      associated with RABV replication levels. Virus isolates from crab eating fox and
      marmoset had a longer evolution period and higher survival rate suggesting that
      the evolution period may contribute to the outcome. RABV virus variants had
      independent characteristics that determine the clinical evolution and survival of
      the infected mice. 

PMID- 26303006
TI  - Identifying a key host in an acanthocephalan-amphipod system.
AB  - Trophically transmitted parasites may use multiple intermediate hosts, some of
      which may be 'key-hosts', i.e. contributing significantly more to the completion
      of the parasite life cycle, while others may be 'sink hosts' with a poor
      contribution to parasite transmission. Gammarus fossarum and Gammarus roeseli are
      sympatric crustaceans used as intermediate hosts by the acanthocephalan
      Pomphorhynchus laevis. Gammarus roeseli suffers higher field prevalence and is
      less sensitive to parasite behavioural manipulation and to predation by
      definitive hosts. However, no data are available on between-host differences in
      susceptibility to P. laevis infection, making it difficult to untangle the
      relative contributions of these hosts to parasite transmission. Based on results
      from estimates of prevalence in gammarids exposed or protected from predation and
      laboratory infections, G. fossarum specimens were found to be more susceptible to
      P. laevis infection. As it is more susceptible to both parasite infection and
      manipulation, G. fossarum is therefore a key host for P. laevis transmission. 

PMID- 26303007
TI  - Differential peptide expression in the central nervous system of the land snail
      Theba pisana, between active and aestivated.
AB  - Hypometabolism is a physiological state of dormancy entered by many animals in
      times of environmental stress. There are gaps in our understanding of the
      molecular components used by animals to achieve this metabolic state. The
      availability of genomic and transcriptome data can be useful to study the process
      of hypometabolism at the molecular level. In this study, we use the land snail
      Theba pisana to identify peptides that may be involved in the hypometabolic state
      known as aestivation. We found a total of 22 neuropeptides in the central nervous
      system (CNS) that were differentially produced during activity and aestivation
      based on mass spectral-based neuropeptidome analysis. Of these, 4 were
      upregulated in active animals and 18 were upregulated in aestivation. A
      neuropeptide known to regulate muscle contractions in a variety of molluscs, the
      small cardioactive peptide A (sCAPA), and a peptide of yet unknown function
      (termed Aestivation Associated Peptide 12) were chosen for further investigation
      using temporal and spatial expression analysis of the precursor gene and peptide.
      Both peptides share expression within regions of the CNS cerebral ganglia and
      suboesophageal ganglia. Relative transcript abundance suggests that regulation of
      peptide synthesis and secretion is post-transcriptional. In summary, we provide
      new insights into the molecular basis of the regulation of aestivation in land
      snails through CNS peptide control.

PMID- 26303005
TI  - Viral precursor protein P3 and its processed products perform discrete and
      essential functions in the poliovirus RNA replication complex.
AB  - The differential use of protein precursors and their products is a key strategy
      used during poliovirus replication. To characterize the role of protein
      precursors during replication, we examined the complementation profiles of
      mutants that inhibited 3D polymerase or 3C-RNA binding activity. We showed that
      3D entered the replication complex in the form of its precursor, P3 (or 3CD), and
      was cleaved to release active 3D polymerase. Furthermore, our results showed that
      P3 is the preferred precursor that binds to the 5'CL. Using reciprocal
      complementation assays, we showed that one molecule of P3 binds the 5'CL and that
      a second molecule of P3 provides 3D. In addition, we showed that a second
      molecule of P3 served as the VPg provider. These results support a model in which
      P3 binds to the 5'CL and recruits additional molecules of P3, which are cleaved
      to release either 3D or VPg to initiate RNA replication. 

PMID- 26303008
TI  - Longitudinal Analysis of Adherence to First-Line Antiretroviral Therapy: Evidence
      of Treatment Sustainability from an Indian HIV Cohort.
AB  - INTRODUCTION: Given the chronic nature of HIV infection and the need for life
      long antiretroviral therapy (ART), maintaining long-term optimal adherence is an
      important strategy for maximizing treatment success. In order to understand
      better the dynamic nature of adherence behaviors in India where complex cultural
      and logistic features prevail, we assessed the patterns, trajectories and time
      dependent predictors of adherence levels in relation to virological failure among
      individuals initiating first-line ART in India. METHODS: Between July 2010 and
      August 2013, eligible ART-naive HIV-infected individuals newly initiating first
      line ART within the national program at three sites in southern India were
      enrolled and monitored for two years. ART included zidovudine/stavudine/tenofovir
      plus lamivudine plus nevirapine/efavirenz. Patients were assessed using clinical,
      laboratory and adherence parameters. Every three months, medication adherence was
      measured using pill count, and a structured questionnaire on adherence barriers
      was administered. Optimal adherence was defined as mean adherence >=95%.
      Statistical analysis was performed using a bivariate and a multivariate model of
      all identified covariates. Adherence trends and determinants were modeled as rate
      ratios using generalized estimating equation analysis in a Poisson distribution.
      RESULTS: A total of 599 eligible ART-naive patients participated in the study,
      and contributed a total of 921 person-years of observation time. Women
      constituted 43% and mean CD4 count prior to initiating ART was 192 cells/mm3.
      Overall mean adherence among all patients was 95.4%. The proportion of patients
      optimally adherent was 75.6%. Predictors of optimal adherence included older age
      (>=40 years), high school-level education and beyond, lower drug toxicity-related
      ART interruption, full disclosure, sense of satisfaction with one's own health
      and patient's perception of having good access to health-care services. Adherence
      was inversely proportional to virological failure (IRR 0.55, 95%CI 0.44-0.69
      p<0.001). Drug toxicity and stigma-related barriers were significantly associated
      with virological failure, while forgetfulness was not associated with virological
      failure. CONCLUSION: Our study highlights the overall high level of medication
      adherence among individuals initiating ART within the Indian national program.
      Primary factors contributing towards poor adherence and subsequent virological
      failure in the proportion of individuals with poor adherence included drug
      toxicity, perceived stigma and poor access to health care services. Strategies
      that may contribute towards improved adherence include minimizing drug
      interruptions for medical reasons, use of newer ART regimens with better safety
      profiles and increasing access with more link ART centers that decentralize ART
      dispensing systems to individuals.

PMID- 26303009
TI  - Prevalence of psychotic disorders in an urban area of France.
AB  - BACKGROUND: Most data on the prevalence of psychotic disorders is limited to
      global estimates or restricted to schizophrenia. Consequently, there is limited
      information available about the prevalence of psychotic disorders more widely and
      outwith age and sex - specific prevalence values. The objective of this study is
      to provide period prevalence estimates, detailed by gender and age groups, for
      treated psychotic disorders in an adult population (aged 18 years and over) from
      an urban area in France. METHODS: Prospective reporting of cases treated over an
      8-week period complemented by several methods estimating the number of
      potentially missed cases, including a leakage study. The study took place in an
      urban, well defined catchment area, with a population of 67 430 at risk subjects
      living in the east of a Paris suburb. RESULTS: The observed prevalence was of
      3.72 per 1000 subjects at risk; after adjustment for potentially lost cases the
      estimate was of 4.60 per 1000 subjects at risk. Observed prevalence was higher in
      men (4.71 per 1000, Relative Risk = 1.68) and in the 35-45 age-band (6.05 per
      1000, Relative Risk = 1.93). CONCLUSION: Global prevalence estimates of psychotic
      disorders in this study are in line with expected values based on studies
      conducted in other countries. Careful consideration of the causes of missed cases
      and gathering of complementary data are essential and could result in significant
      changes in prevalence estimates. Detailed estimates (by age) suggest that treated
      psychosis might not be a lifelong condition.

PMID- 26303011
TI  - PA401, a novel CXCL8-based biologic therapeutic with increased glycosaminoglycan
      binding, reduces bronchoalveolar lavage neutrophils and systemic inflammatory
      markers in a murine model of LPS-induced lung inflammation.
AB  - RATIONALE: Neutrophils play a fundamental role in a number of chronic lung
      diseases. Among the mediators of their recruitment to the lung, CXCL8 (IL-8) is
      considered to be one of the major players. CXCL8 exerts its chemotactic activity
      by binding to its GPCR receptors (CXCR1/R2) located on neutrophils, as well as
      through interactions with glycosaminoglycans (GAGs) on cell surfaces including
      those of the microvascular endothelium. Binding to GAG co-receptors is required
      to generate a solid-phase haptotactic gradient and to present IL-8/CXCL8 in a
      proper conformation to its receptors on circulating neutrophils. METHODS: We have
      engineered increased GAG-binding affinity into human CXCL8, thereby obtaining a
      competitive inhibitor that displaces wild-type IL-8/CXCL8 from GAGs. By
      additionally knocking-out the GPCR binding domain of the chemokine, we generated
      a dominant negative protein (dnCXCL8; PA401) with potent anti-inflammatory
      characteristics proven in vivo in a murine model of LPS-induced lung inflammation
      (Adage et al., 2015). Here we have further investigated PA401 activity in this
      pulmonary model by evaluating plasma changes induced by LPS on white blood cells
      (WBC) and a broad range of inflammatory markers, especially chemokines, by
      addressing immediate effects of PA401 on these parameters in healthy and LPS
      exposed mice. RESULTS: Aerosolized LPS induced a significant increase in
      bronchoalveolar lavage (BAL) neutrophils after 3 and 7h, as well as an increase
      in total WBC and changes in 21 of the 59 measured plasma markers, mostly
      belonging to the chemokine family. PA401 treatment in saline exposed mice didn't
      induce major changes in any of the measured parameters. When administered to LPS
      aerosolized mice, PA401 caused a significant normalization of KC/mCXCL1 and other
      inflammatory markers, as well as of blood WBC count. In addition, BAL neutrophils
      were significantly reduced, confirming the previously observed lung anti
      inflammatory activity of PA401 in this experiment. CONCLUSIONS: PA401 is a new
      promising biologic therapeutic with a novel and unique mechanism of action for
      interfering with neutrophilic lung inflammation, that also normalizes plasma
      inflammatory markers.

PMID- 26303010
TI  - Effects of sleep and wake on astrocytes: clues from molecular and ultrastructural
      studies.
AB  - BACKGROUND: Astrocytes can mediate neurovascular coupling, modulate neuronal
      excitability, and promote synaptic maturation and remodeling. All these functions
      are likely to be modulated by the sleep/wake cycle, because brain metabolism,
      neuronal activity and synaptic turnover change as a function of behavioral state.
      Yet, little is known about the effects of sleep and wake on astrocytes. RESULTS:
      Here we show that sleep and wake strongly affect both astrocytic gene expression
      and ultrastructure in the mouse brain. Using translating ribosome affinity
      purification technology and microarrays, we find that 1.4 % of all astrocytic
      transcripts in the forebrain are dependent on state (three groups, sleep, wake,
      short sleep deprivation; six mice per group). Sleep upregulates a few select
      genes, like Cirp and Uba1, whereas wake upregulates many genes related to
      metabolism, the extracellular matrix and cytoskeleton, including Trio, Synj2 and
      Gem, which are involved in the elongation of peripheral astrocytic processes.
      Using serial block face scanning electron microscopy (three groups, sleep, short
      sleep deprivation, chronic sleep restriction; three mice per group, >100 spines
      per mouse, 3D), we find that a few hours of wake are sufficient to bring
      astrocytic processes closer to the synaptic cleft, while chronic sleep
      restriction also extends the overall astrocytic coverage of the synapse,
      including at the axon-spine interface, and increases the available astrocytic
      surface in the neuropil. CONCLUSIONS: Wake-related changes likely reflect an
      increased need for glutamate clearance, and are consistent with an overall
      increase in synaptic strength when sleep is prevented. The reduced astrocytic
      coverage during sleep, instead, may favor glutamate spillover, thus promoting
      neuronal synchronization during non-rapid eye movement sleep.

PMID- 26303012
TI  - Inclusion of functional information from perfusion SPECT improves predictive
      value of dose-volume parameters in lung toxicity outcome after radiotherapy for
      non-small cell lung cancer: A prospective study.
AB  - BACKGROUND AND PURPOSE: To compare functional and standard dose-volume parameters
      as predictors of postradiation pulmonary toxicity in lung cancer patients
      undergoing curative chemo-radiotherapy (RT) studied prospectively. MATERIAL AND
      METHODS: A total of 58 patients treated with Intensity Modulated RT (60-66Gy)
      were analysed. Standard dose-volume parameters were extracted from treatment
      planning computed tomography (CT) scans. Corresponding functional dose-volume
      parameters were calculated from perfusion single-photon emission computed
      tomography (SPECT). Primary end-point was radiation pneumonitis (RP) grade 2-5.
      RESULTS: Functional mean lung dose (MLD) and lung volumes receiving 5, 10, 20 and
      30Gy (V5-V30, respectively) revealed high correlation with corresponding standard
      parameters (r>0.8). Standard MLD, V20 and V30 were significantly higher in
      patients with RP (p=0.01). All functional parameters were significantly higher in
      the RP patients (p<0.03). In multivariate analysis functional parameters produced
      superior risk estimates, while all standard parameters, except V30, were not
      related to the risk of RP. Area under the curve (AUC) for functional metrics
      generally exceeded the AUC for corresponding standard parameters, but they were
      not significantly different from each other. CONCLUSION: SPECT-based functional
      parameters were better to predict the risk of RP compared to standard CT-based
      dose-volume parameters. Functional parameters may be useful to guide radiotherapy
      planning in order to reduce the risk of radiation-induced toxicity.

PMID- 26303013
TI  - The yield of DNA double strand breaks determined after exclusion of those forming
      from heat-labile lesions predicts tumor cell radiosensitivity to killing.
AB  - BACKGROUND AND PURPOSE: The radiosensitivity to killing of tumor cells and in
      field normal tissue are key determinants of radiotherapy response. In vitro
      radiosensitivity of tumor- and normal-tissue-derived cells often predicts
      radiation response, but high determination cost in time and resources compromise
      utility as routine response-predictor. Efforts to use induction or repair of DNA
      double-strand-breaks (DSBs) as surrogate-predictors of cell radiosensitivity to
      killing have met with limited success. Here, we re-visit this issue encouraged by
      our recent observations that ionizing radiation (IR) induces not only promptly
      forming DSBs (prDSBs), but also DSBs developing after irradiation from the
      conversion to breaks of thermally-labile sugar-lesions (tlDSBs). MATERIALS AND
      METHODS: We employ pulsed-field gel-electrophoresis and flow-cytometry protocols
      to measure total DSBs (tDSB=prDSB+tlDSBs) and prDSBs, as well as gammaH2AX and
      parameters of chromatin structure. RESULTS: We report a fully unexpected and in
      many ways unprecedented correlation between yield of prDSBs and radiosensitivity
      to killing in a battery of ten tumor cell lines that is not matched by yields of
      tDSBs or gammaH2AX, and cannot be explained by simple parameters of chromatin
      structure. CONCLUSIONS: We propose the introduction of prDSBs-yield as a novel
      and powerful surrogate-predictor of cell radiosensitivity to killing with
      potential for clinical application.

PMID- 26303014
TI  - A phase 2 randomized study to compare short course palliative radiotherapy with
      short course concurrent palliative chemotherapy plus radiotherapy in advanced and
      unresectable head and neck cancer.
AB  - BACKGROUND: Treatment of unresectable HNSCC is not well defined and has a poor
      outcome. This study has been designed to address the unmet needs of such groups
      of patients with primary end points of (a) proportion of patients eligible for
      radical treatment in each arm (b) loco-regional disease control at 6months
      between two arms. MATERIALS AND METHODS: Locally advanced and unresectable HNSCC
      patients (except Nasopharynx and Larynx) unfit for radical treatment were
      randomized to arm A [short course RT alone (4Gy/#/day for 5days)] or arm B [RT as
      arm A+concurrent cisplatin at 6mg/m(2)/day IV bolus for 5days]. Those with at
      least PR were taken for further RT to complete biological equivalent dose of
      70Gy, in both the arms. In arm B, concurrent CDDP at a dose of 40mg/m(2)/week was
      administered. RESULTS: 114 patients (57 in each arm) were randomized but 111 were
      analyzable. 15 (27.27%) patients in arm A and 28 (50%) patients in arm B had ?PR
      (p=0.01) however patients taken for FRT were 14 (25.45%) and 26 (46.42%) in arms
      A and B respectively (p=0.02). Locoregional control i.e. (CR+PR) at 6months was
      16.36% in arm A versus 32.14% in arm B (p=0.15). Median PFS (arm A - 3.2months,
      arm B - 6.2months; p=0.02) and OS (arm A - 5.9months, arm B - 10.1months; p=0.03)
      was significantly more in arm B. There was relative improvement in quality of
      life for most parameters in arm B. CONCLUSION: Concurrent low dose CTRT can be an
      effective treatment modality in advanced and incurable HNSCC. However, a larger
      phase III trial is required.

PMID- 26303015
TI  - Carcinoembryonic antigen has prognostic value for tumor downstaging and
      recurrence in rectal cancer after preoperative chemoradiotherapy and curative
      surgery: A multi-institutional and case-matched control study of KROG 14-12.
AB  - BACKGROUND AND PURPOSE: The Korean Radiation Oncology Group evaluated the
      significance of carcinoembryonic antigen (CEA) levels both as a predictor of
      tumor response after CRT and as a prognosticator for recurrence-free survival.
      METHODS AND MATERIALS: 1804 rectal cancer patients, staged cT3-4N0-2M0,
      participated in a multicenter study. The patients were administered preoperative
      radiation of 50.4 Gy in 28 fractions with 5-FU or capecitabine, followed by total
      mesorectal excision. Patients with elevated CEA levels (>5 ng/mL) were matched at
      a 1 (n=595):1 (n=595) ratio with patients with normal CEA (?5 ng/mL). The tumor
      response after CRT and the recurrence-free survival (RFS) rates were evaluated
      and compared between two arms. RESULTS: An elevated CEA level (p<0.001) was
      determined to be a significant negative predictor of downstaging after CRT. The
      downstaging rate was 42.9% for normal CEA and 23.4% for elevated CEA. A
      multivariate analysis also revealed that cT (p=0.021) and cN classification
      (p=0.001), tumor size (p=0.002), and tumor location from the anal verge (p=0.006)
      were significant predictors for tumor downstaging. The 5-year RFS rates were
      significantly higher for the normal CEA arm than for the elevated CEA arm (74.2
      vs. 63.5%, p<0.001). CONCLUSIONS: Elevated CEA (>5 ng/mL) is a negative predictor
      of tumor downstaging after CRT and also has a negative impact on RFS in rectal
      cancer.

PMID- 26303016
TI  - A plasmonic nanorod that walks on DNA origami.
AB  - In nano-optics, a formidable challenge remains in precise transport of a single
      optical nano-object along a programmed and routed path toward a predefined
      destination. Molecular motors in living cells that can walk directionally along
      microtubules have been the inspiration for realizing artificial molecular
      walkers. Here we demonstrate an active plasmonic system, in which a plasmonic
      nanorod can execute directional, progressive and reverse nanoscale walking on two
      or three-dimensional DNA origami. Such a walker comprises an anisotropic gold
      nanorod as its 'body' and discrete DNA strands as its 'feet'. Specifically, our
      walker carries optical information and can in situ optically report its own
      walking directions and consecutive steps at nanometer accuracy, through dynamic
      coupling to a plasmonic stator immobilized along its walking track. Our concept
      will enable a variety of smart nanophotonic platforms for studying dynamic light
      matter interaction, which requires controlled motion at the nanoscale well below
      the optical diffraction limit. 

PMID- 26303017
TI  - In vitro and in vivo assessment of the genotoxicity and antigenotoxicity of the
      Filipendula hexapetala and Filipendula ulmaria methanol extracts.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The two species of Filipendula genus, Filipendula
      hexapetala Gilib. and Filipendula ulmaria (L.) Maxim are a traditional herbal
      medicine widely used to treat haemorrhoids, diarrhoea, fever, rheumatism and
      arthritic pain, kidney problems, to stop bleeding, and the common cold, as well
      as food supplements. However, no scientific study has been performed to validate
      genotoxic and/or antigenotoxic potentials of these two Filipendula species. AIM
      OF THE STUDY: The aim of the present study was to examine the genotoxic and
      possible in vitro and in vivo DNA protection potential of methanol extracts of F.
      hexapetala and F. ulmaria. MATERIALS AND METHODS: The genotoxicity of different
      concentrations of F. hexapetala and F. ulmaria methanol extracts from roots and
      aerial parts (20, 40 and 80 mg/ml), mixed with standard food for Drosophila, was
      evaluated in vivo in the anterior midgut of Drosophila melanogaster using a
      modified alkaline comet assay. The protective effects of the highest dose of
      extracts were observed in somatic cells of third-instar larvae against ethyl
      methanesulphonate (EMS)-induced genotoxicity. Also, DNA protection activity of
      methanol extracts from F. hexapetala and F. ulmaria (100, 200, and 400 MUg/ml)
      against hydroxyl radical-induced DNA damage was determined under in vitro
      conditions. RESULTS: The results showed that methanol extracts from the root and
      aerial part of F. hexapetala at a concentration of 20mg/ml indicated the absence
      of genotoxicity. Also, there were no statistically significant differences in
      total scores between any of the groups treated with F. ulmaria root extract and
      the negative control group, while F. ulmaria aerial part extract possess weak
      genotoxic effects depending on the concentrations. The percentage reduction in
      DNA damage was more evident in the group of larvae simultaneously treated with
      EMS and the highest dose of F. hexapetala root or aerial part extracts and F.
      ulmaria root extract (91.02, 80.21, and 87.5%, respectively) and less expressive
      in the group simultaneously treated with F. ulmaria aerial part extract (54.7%).
      F. hexapetala root and aerial part extracts and F. ulmaria root extract possess
      strong capabilities to protect DNA from being damaged by hydroxyl radicals.
      CONCLUSIONS: It can be concluded that F. hexapetala root and aerial part extracts
      and F. ulmaria root extract demonstrated the absence of genotoxic activity. The
      extracts appeared to have antigenotoxic effect, reducing the levels of DNA damage
      induced by EMS by more than 80%. Also, F. hexapetala root and aerial part
      extracts and F. ulmaria root extracts could effectively protect against hydroxyl
      radical-induced DNA damage.

PMID- 26303019
TI  - Glomerular Filtration Rate and Aging: Another Longitudinal Study--A Long Time
      Coming!

PMID- 26303018
TI  - Prevalence and etiologies of adult communication disabilities in the United
      States: Results from the 2012 National Health Interview Survey.
AB  - BACKGROUND: Communication disabilities, including speech, language and voice
      disabilities, can significantly impact a person's quality of life, employment and
      health status. Despite this, little is known about the prevalence and etiology of
      communication disabilities in the general adult population. OBJECTIVES: To assess
      the prevalence and etiology of communication disabilities in a nationally
      representative adult sample. METHODS: We conducted a cross-sectional study and
      analyzed the responses of non-institutionalized adults to the Sample Adult Core
      questionnaire within the 2012 National Health Interview Survey. We used
      respondents' self-report of having a speech, language or voice disability within
      the past year and receiving a diagnosis for one of these communication
      disabilities, as well as the etiology of their communication disability. We
      additionally examined the responses by subgroups, including sex, age, race and
      ethnicity, and geographical area. RESULTS: In 2012 approximately 10% of the US
      adult population reported a communication disability, while only 2% of adults
      reported receiving a diagnosis. The rates of speech, language and voice
      disabilities and diagnoses varied across gender, race/ethnicity and geographic
      groups. The most common response for the etiology of a communication disability
      was "something else." CONCLUSIONS: Improved understanding of population
      prevalence and etiologies of communication disabilities will assist in
      appropriately directing rehabilitation and medical services; potentially reducing
      the burden of communication disabilities.

PMID- 26303020
TI  - Inpatient Treatment for Severe Nonsurgical Dermatological Disorders: Prevalence,
      Care Infrastructure and Reimbursement in Switzerland.
AB  - BACKGROUND: Since 2012, Swiss inpatient dermatology is funded through a flat rate
      payment system based on diagnosis-related groups (DRGs). OBJECTIVE: To analyze
      the reimbursement of nonsurgically treated severe disorders of the skin under the
      system called SwissDRG. METHODS: Three retrospective, cross-sectional cohort
      studies were performed. Data sets were received from the Swiss Federal Office of
      Statistics (1,285,685 retained records), the five Swiss university hospitals
      (370,964 retained records) and our center (72,211 retained records). RESULTS:
      Cases accounted for 0.04% of all hospitalizations nationwide, with 43.7% treated
      at university hospitals. Treatment at university hospitals produced a mean loss
      of USD 3,711 per case. Lyell syndrome cases were especially underfunded (mean
      loss USD 31,906). Extra-county admissions and direct referrals were significant
      predictors of total inpatient costs (p = 0.019 and p < 0.001, respectively).
      CONCLUSIONS: We suggest grouping Lyell syndrome cases into burn DRGs and
      evaluating extra-county admissions and direct inpatient referrals as DRG split
      criteria.

PMID- 26303021
TI  - [Prenatal management of the risk of maternofetal infection in cases of PPROM].
AB  - Preterm premature rupture of membranes (PPROM) occurs in 3 % of pregnancies and
      is responsible for 30 % of premature births. The risks described in cases of
      PPROM are those of prematurity, acute maternal-fetal infection, cord prolapse,
      and abruptio placentae. The main objective of prenatal care is to reduce and
      anticipate the risk of perinatal infection and morbidity superimposed, but the
      predictive value of prenatal monitoring for the maternal-fetal infection
      prediction is low. Antibiotics are recommended routinely in PPROM cases.
      Tocolysis should not be continued more than 48h before 32 weeks gestation. Before
      32 or 34 WG, a gain of 1 week of gestational age significantly reduces mortality
      and neonatal morbidity, and expectant management is usually preferred. French
      recommendations for clinical practice for expectant management or labor induction
      leave open either expectant management or labor induction after 34 WG. Between 34
      and 37 weeks, the risk of rare severe morbidity related to prematurity are to be
      balanced against those of an acute infection or a maternal-fetal placental
      abruption. A large randomized trial comparing expectant and labor induction in
      cases of PPROM between 33 and 37 weeks showed no benefit of labor induction but
      did not have the power to explore rare and severe complications. 

PMID- 26303022
TI  - The role of sleep timing in children's observational learning.
AB  - Acquisition of information can be facilitated through different learning
      strategies, classically associated with either declarative or procedural memory
      modalities. The consolidation of the acquired information has been positively
      associated with sleep. In addition, subsequent performance was better when
      acquisition was quickly followed by sleep, rather than daytime wakefulness. Prior
      studies with adults have indicated the viability of the alternative learning
      strategy of observational learning for motor skill acquisition, as well as the
      importance of sleep and sleep timing. However, relatively little research has
      been dedicated to studying the importance of sleep for the consolidation of
      procedural memory in children. Therefore, this study investigated whether
      children could encode procedural information through observational learning, and
      whether sleep timing could affect subsequent consolidation and performance.
      School-aged children aged 9-12years (N=86, 43% male, Mage=10.64years, SD=.85)
      were trained on a procedural fingertapping task through observation, either in
      the morning or evening; creating immediate wake and immediate sleep groups,
      respectively. Performance was evaluated the subsequent evening or morning on
      either a congruent or incongruent task version. Observation and task execution
      was conducted using an online interface, allowing for remote participation.
      Performance of the immediate wake group was lower for a congruent version,
      expressed by a higher error rate, opposed to an incongruent version; an effect
      not observed in the immediate sleep group. This finding showed that observational
      learning did not improve performance in children. Yet, immediate sleep prevented
      performance reduction on the previously observed task. These results support a
      benefit of sleep in observational learning in children, but in a way different
      from that seen in adults, where sleep enhanced performance after learning by
      observation. 

PMID- 26303023
TI  - Brain ventricular dimensions and relationship to outcome in adult patients with
      bacterial meningitis.
AB  - BACKGROUND: Experimental studies suggest that changes in brain ventricle size are
      key events in bacterial meningitis. This study investigated the relationship
      between ventricle size, clinical condition and risk of poor outcome in patients
      with bacterial meningitis. METHODS: Adult patients diagnosed with bacterial
      meningitis admitted to two departments of infectious diseases from 2003 through
      2010 were identified. Clinical and biochemical data as well as cerebral computed
      tomographic images were collected. The size of the brain ventricles were
      presented as a Ventricle to Brain Ratio (VBR). Normal range of VBR was defined
      from an age matched control group. A multivariate analysis was performed to
      identify predictors of 30-day mortality. RESULTS: One hundred and seven patients
      were included. Eighty-one patients had a CT scan at the time of diagnosis. VBR
      was identified as an independent risk factor of 30-day mortality, Mortality Rate
      Ratio: 6.03 (95 % confidence interval: 1.61-22.64, p = 0.008) for highest versus
      lowest tertile. A VBR deviating more than 2 standard deviations from the normal
      range was associated with increased mortality. CONCLUSIONS: Brain ventricles are
      commonly subject to marked changes in size as a consequence of meningitis.
      Increased brain ventricle size in the acute phase of bacterial meningitis was
      associated with increased mortality.

PMID- 26303024
TI  - Selective enrichment of mycobacterial proteins from infected host macrophages.
AB  - Upon infection, Mycobacterium tuberculosis (Mtb) deploys specialized secretion
      machinery to deliver virulent proteins with the capacity to modulate a variety of
      host-cellular pathways. Studies on the identification of intra-macrophage Mtb
      proteins, however, are constricted by an inability to selectively enrich these
      virulent effectors against overwhelming protein content of the host. Here, we
      introduce an Mtb-selective protein labeling method based on genetic incorporation
      of azidonorleucine (Anl) through the expression of a mutant methionyl-tRNA
      synthetase. Exclusive incorporation of Anl, into native Mtb proteins, provided a
      click handle to pull out low abundant secretory proteins from the lysates of
      infected cells. Further, temporal secretome profiling, upon infection with
      strains of varying degree of virulence, revealed the proficiency of virulent Mtb
      to secrete chaperones. This ability contributed at least partially to the
      mycobacterial virulence-specific suppression of ER stress in the host macrophage,
      representing an important facet of mycobacterial virulence. The Anl labeling
      approach should facilitate new exciting opportunities for imaging and proteomic
      investigations of differently virulent Mtb isolates to understand determinants of
      pathogenicity. 

PMID- 26303025
TI  - Time scale dependence of the center of pressure entropy: What characteristics of
      the neuromuscular postural control system influence stabilographic entropic half
      life?
AB  - The center of pressure (COP) movement in studies of postural control reveals a
      highly regular structure (low entropy) over short time periods and a highly
      irregular structure over large time scales (high entropy). Entropic half-life
      (EnHL) is a novel measure that quantifies the time over which short-term temporal
      correlations in a time series deteriorate to an uncorrelated, random structure.
      The current study suggested and tested three hypotheses about how characteristics
      of the neuromuscular postural control system may affect stabilometric EnHL: (H1)
      control system activity hypothesis: EnHL decreases with increased frequency of
      control system interventions adjusting COP motion; (H2) abundance of states
      hypothesis: EnHL decreases with increased number of mechanically equivalent
      states available to the postural system; and (H3) neurologic process hierarchy
      hypothesis: EnHL increases if postural control functions shift from the spinal
      level to the motor cortex. Thirty healthy participants performed quiet stance
      tests for 90 s in 18 different conditions: stance (bipedal, one-legged, and
      tandem); footwear (bare foot, regular sports shoe, and rocker sole shoes); and
      simultaneous cognitive task (two-back working memory task, no challenge). A four
      way repeated-measures ANOVA revealed significant changes in EnHL for the
      different stance positions and for different movement directions (medio-lateral,
      anterior-posterior). These changes support H1 and H2. Significant differences
      were also found between rocker sole shoes and normal or barefoot standing, which
      supports H3. This study contributes to the understanding of how and why EnHL is a
      useful measure to monitor neuromuscular control of balance.

PMID- 26303026
TI  - Updating representations of temporal intervals.
AB  - Effectively engaging with the world depends on accurate representations of the
      regularities that make up that world-what we call mental models. The success of
      any mental model depends on the ability to adapt to changes-to 'update' the
      model. In prior work, we have shown that damage to the right hemisphere of the
      brain impairs the ability to update mental models across a range of tasks. Given
      the disparate nature of the tasks we have employed in this prior work (i.e.
      statistical learning, language acquisition, position priming, perceptual
      ambiguity, strategic game play), we propose that a cognitive module important for
      updating mental representations should be generic, in the sense that it is
      invoked across multiple cognitive and perceptual domains. To date, the majority
      of our tasks have been visual in nature. Given the ubiquity and import of
      temporal information in sensory experience, we examined the ability to build and
      update mental models of time. We had healthy individuals complete a temporal
      prediction task in which intervals were initially drawn from one temporal range
      before an unannounced switch to a different range of intervals. Separate groups
      had the second range of intervals switch to one that contained either longer or
      shorter intervals than the first range. Both groups showed significant positive
      correlations between perceptual and prediction accuracy. While each group updated
      mental models of temporal intervals, those exposed to shorter intervals did so
      more efficiently. Our results support the notion of generic capacity to update
      regularities in the environment-in this instance based on temporal information.
      The task developed here is well suited to investigations in neurological patients
      and in neuroimaging settings. 

PMID- 26303028
TI  - Differential behaviour of cationic triphenylamine derivatives in fixed and living
      cells: triggering and imaging cell death.
AB  - Triphenylamines are on/off fluorescent DNA minor groove binders, allowing nuclear
      staining of fixed cells. By contrast, they accumulate in the cytoplasm of living
      cells and efficiently trigger cell apoptosis upon prolonged visible light
      irradiation. This process occurs concomitantly with their subcellular re
      localization to the nucleus, enabling fluorescence imaging of apoptosis. 

PMID- 26303027
TI  - A comparative study between Wuweizi seed and its post-ethanol extraction residue
      in normal and hypercholesterolemic mice.
AB  - BACKGROUND: At the present, a shift from drug therapy, especially herbal therapy,
      to dietary supplementation is a trend in the management of dyslipidemia and
      related diseases. Therefore, the optimal utilization of herbal resource is
      important for a sustainable development of herbal medicine. Here, we compared the
      effects of dietary supplementation with Chinese medicine Schisandrae Chinensis
      Fructus seed (FSC-S) and the post-ethanol extraction residue of FSC-S (FSC-SpEt)
      on normal diet-fed (normal) and experimental hypercholesterolemic (HCL) mice.
      METHODS: Male ICR mice (n = 10 in each group), weighing 17-21 g, were fed with
      normal diet (ND) or high cholesterol/bile salt (1/0.3 %, w/w) diet (HCBD) with or
      without supplemented with FSC-S, FSC-SpEt), or lipid-lowering agent fenofibrate
      (FF). Ten days later, serum/hepatic lipid and glucose (GLU) levels, body weight,
      organ/epididymal fat masses, and food/water intake were measured. Lipid level
      measurements included those of total cholesterol (TC), triglyceride (TG), high
      density lipoprotein (HDL), low density lipoprotein (LDL), HDL/LDL ratio, LDL/HDL
      ratio, and non-HDL (N-HDL). RESULTS: Supplementation with FSC-S and FSC-SpEt
      increased serum TC (by 64 and 25 %, respectively) and LDL (by 60 and 27 %,
      respectively) in normal mice. FSC-S supplementation elevated serum TC, TG, HDL,
      LDL, and LDL/HDL ratio (up to 64, 118, 77, 197, and 51 %, respectively) in HCL
      mice. FSC-SpEt supplementation reduced serum TG (by 15 %) and LDL/HDL ratio (by
      18 %), as well as increased serum HDL (by 22 %) and HDL/LDL ratio (by 21 %) in
      HCBD-fed mice. FSC-S decreased hepatic TC (by 19 %) contents and increased
      hepatic TG contents by 14 % in normal mice. FSC-S reduced hepatic GLU level in
      both normal and HCL mice by 24 and 22 %, respectively. Hepatic TC and TG contents
      were lowered in FSC-SpEt-supplemented normal mice by 16 and 20 %, respectively.
      The body/fatty masse and food intake were lowered, but the feed efficiency index
      (FEI), weight gain per unit of food ingested, was increased in FSC-S-supplemented
      normal and HCL mice. FF supplements reduced serum/hepatic lipids, hepatic GLU
      contents, and epididymal fat mass, but it induced hepatomegaly and high serum
      alanine aminotransferase (ALT) activity in normal and/or HCL mice. CONCLUSION:
      The ensemble of results indicated that while FSC-SpEt supplementation is
      beneficial for the treatment of hyperlipidemia/fatty liver, FSC-S is potentially
      useful for the management of overweight/obesity.

PMID- 26303029
TI  - The media and access issues: content analysis of Canadian newspaper coverage of
      health policy decisions.
AB  - BACKGROUND: Previous studies have demonstrated how the media has an influence on
      policy decisions and healthcare coverage. Studies of Canadian media have shown
      that news coverage often emphasizes and hypes certain aspects of high profile
      health debates. We hypothesized that in Canadian media coverage of access to
      healthcare issues about therapies and technologies including for rare diseases,
      the media would be largely sympathetic towards patients, thus adding to public
      debate that largely favors increased access to healthcare-even in the face of
      equivocal evidence regarding efficacy. METHODS: In order to test this hypothesis,
      we conducted a content analysis of 530 news articles about access to health
      therapies and technologies from 15 major Canadian newspapers over a 10-year
      period. Articles were analyzed for the perspectives presented in the articles and
      the types of reasons or arguments presented either for or against the particular
      access issue portrayed in the news articles. RESULTS: We found that news media
      coverage was largely sympathetic towards increasing healthcare funding and ease
      of access to healthcare (77.4 %). Rare diseases and orphan drugs were the most
      common issues raised (22.6 %). Patients perspectives were often highlighted in
      articles (42.3 %). 96.8 % of articles discussed why access to healthcare needs to
      increase, and discussion that questioned increased access was only included in
      33.6 % articles. CONCLUSION: We found that news media favors a patient access
      ethos, which may contribute to a difficult policy-making environment.

PMID- 26303030
TI  - Neuroprotective Effect of the Endogenous Amine 1MeTIQ in an Animal Model of
      Parkinson's Disease.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder that is hallmarked by
      pathological changes associated with the death of dopaminergic neurons,
      particularly in the extrapyramidal system (substantia nigra pars compacta,
      striatum) of the brain. Although the causes of slow neuronal death in PD are
      unknown, both genetic and environmental factors are likely involved. Endogenous
      isoquinolines, such as 1-benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ), present
      in the human brain have been previously reported to participate in the
      pathogenesis of PD. The chronic administration of 1BnTIQ induced parkinsonism in
      primates, and this effect might be associated with idiopathic PD. However,
      another endogenous derivative of tetrahydroisoquinoline, 1-methyl-1,2,3,4
      tetrahydroisoquinoline (1MeTIQ), displays clear neuroprotective properties in the
      brain. In the present study, we investigated the neuroprotective effects of
      1MeTIQ (25 and 50 mg/kg) in an animal model of PD after the chronic
      administration of 1BnTIQ (25 mg/kg). Behavioral analyses demonstrate that both
      acute and repeated treatment with 1MeTIQ completely antagonized 1BnTIQ-induced
      changes in rat locomotor activity. Neurochemical experiments indicate that 1MeTIQ
      co-administered with 1BnTIQ completely antagonized 1BnTIQ-induced reduction in
      the dopamine (DA) concentration in rat brain structures. In conclusion, the
      results demonstrate that 1MeTIQ possesses important neuroprotective properties in
      the animal model of PD and that the rats did not develop tolerance after its
      chronic administration. 

PMID- 26303031
TI  - May progesterone receptor membrane component 1 (PGRMC1) predict the risk of
      breast cancer?
AB  - OBJECTIVE: Our and other studies have pointed on an important role of
      progesterone receptor membrane component 1 (PGRMC1) in development of breast
      cancer, especially in hormone therapy. To investigate if PGRMC1 could be used to
      predict the risk for getting breast cancer, we assessed in tissues of patients
      with primary invasive breast cancer, if the expression of PGRMC1 may be
      associated with the expression of estrogen receptor alpha (ERalpha), progesterone
      receptor (PR), and ki67. METHODS: Samples from 109 patients with breast cancer
      between the years 2008 and 2014 were obtained with the patients' consent. Each
      sample was evaluated for the ERalpha, PR, Ki67, and PGRMC1 expression by
      immunohistochemistry using serial sections from the ame paraffin block comparing
      malignant tissue to benign tissue. RESULTS: Expression of PGRMC1 is increased in
      tumor area compared with non-cancerous tissue and positively correlates with
      ERalpha expression (OR = 1.42 95%CI 1.06-1.91, p = 0.02). No association was
      obtained between expression of PGRMC1 and PR or Ki67. CONCLUSION: It can be
      suggested that women with breast epithelium highly expressing PGRMC1 and in
      interaction with ERalpha may have an increased risk to develop breast cancer,
      especially when treated with hormone therapy.

PMID- 26303032
TI  - Light trapping in randomly arranged silicon nanorocket arrays for photovoltaic
      applications.
AB  - Realization of broadband optical absorption enhancement in thin film c-Si solar
      cells is essential for improving energy conversion efficiency and reducing cost.
      Here, we demonstrate the fabrication of randomly arranged silicon nanorocket
      (SiNR) arrays as a new light trapping structure design for thin film silicon
      solar cells. The optical absorption of the randomly arranged SiNR arrays is
      investigated via finite-difference-frequency-domain (FDTD) simulation. Our
      calculations reveal that the light trapping structures facilitate the coupling of
      incident sunlight into the resonant modes and lead to significant photon
      absorption enhancement across a wide solar spectrum, resulting in ultimate
      efficiencies superior to nanowire and nanohole arrays with the same thickness.
      Our findings indicate that the randomly arranged SiNR arrays fabricated by the
      simple self-assembly and etching approach can have a significant impact on
      performance improvement in thin film silicon solar cells. 

PMID- 26303033
TI  - A Novel Depression Diagnosis Index Using Nonlinear Features in EEG Signals.
AB  - Depression is a mental disorder characterized by persistent occurrences of lower
      mood states in the affected person. The electroencephalogram (EEG) signals are
      highly complex, nonlinear, and nonstationary in nature. The characteristics of
      the signal vary with the age and mental state of the subject. The signs of
      abnormality may be invisible to the naked eyes. Even when they are visible,
      deciphering the minute changes indicating abnormality is tedious and time
      consuming for the clinicians. This paper presents a novel method for automated
      EEG-based diagnosis of depression using nonlinear methods: fractal dimension,
      largest Lyapunov exponent, sample entropy, detrended fluctuation analysis,
      Hurst's exponent, higher order spectra, and recurrence quantification analysis. A
      novel Depression Diagnosis Index (DDI) is presented through judicious combination
      of the nonlinear features. The DDI calculated automatically based on the EEG
      recordings can be used to diagnose depression objectively using just one numeric
      value. Also, these features extracted from nonlinear methods are ranked using the
      t value and fed to the support vector machine (SVM) classifier. The SVM
      classifier yielded the highest classification performance with an average
      accuracy of about 98%, sensitivity of about 97%, and specificity of about 98.5%. 

PMID- 26303034
TI  - Airborne exposure to methylisothiazolinone in paint causing allergic contact
      dermatitis: An Australian perspective.
AB  - An alarming increase in contact allergy to methylisothiazolinone (MI) has been
      noted worldwide. Airborne exposure to MI in paint is an acknowledged occupational
      hazard. We present the first Australian report of airborne allergic contact
      dermatitis (ACD) following exposure to wall paint containing MI.

PMID- 26303035
TI  - De novo donor-specific anti-HLA antibodies mediated rejection in liver-transplant
      patients.
AB  - The incidence and consequences of de novo donor-specific anti-HLA antibodies
      (DSAs) after liver transplantation (LT) are not well known. We investigated the
      incidence, risk factors, and complications associated with de novo DSAs in this
      setting. A total of 152 de novo liver-transplant patients, without preformed anti
      HLA DSAs, were tested for anti-HLA antibodies, with single-antigen bead
      technology, before, at transplantation, at 1, 3, 6 and 12 months after
      transplantation, and thereafter annually and at each time they presented with
      increased liver-enzyme levels until the last follow-up, that is, 34 (1.5-77)
      months. Twenty-one patients (14%) developed de novo DSAs. Of these, five patients
      had C1q-binding DSAs (24%). Younger age, low exposure to calcineurin inhibitors,
      and noncompliance were predictive factors for de novo DSA formation. Nine of the
      21 patients (43%) with de novo DSAs experienced an acute antibody-mediated
      rejection (AMR). Positive C4d staining was more frequently observed in liver
      biopsies of patients with AMR (9/9 vs. 1/12, P < 0.0001). Eight patients received
      a B-cell targeting therapy, and one patient received polyclonal antibodies. Only
      one patient required retransplantation. Patient- and graft-survival rates did not
      differ between patients with and without DSAs. In conclusion, liver-transplant
      patients with liver abnormalities should be screened for DSAs and AMR. 

PMID- 26303037
TI  - Development of the Adult Epilepsy Self-Management Measurement Instrument
      (AESMMI).
AB  - Epilepsy self-management is the total sum of steps that people perform to
      maximize seizure control, to minimize the impact of having a seizure disorder,
      and to maximize quality of life. As part of a phased approach to instrument
      development, we conducted descriptive analyses of data from epilepsy self
      management items covering 10 domains of self-management gathered from 422 adults
      with epilepsy from multiple study sites. Participants most frequently reported
      performing sets of behaviors related to managing treatment and stigma,
      information seeking, managing symptoms, and communicating with providers.
      Behaviors reported with lower frequency were related to seeking social support
      and engaging in wellness behaviors. Significant differences for the domains were
      found for income, gender, and education levels but not for other different
      demographic variables. A subsequent analytic phase, reported in a companion
      article, will use factor analysis to identify and validate the subscale structure
      of the domains. 

PMID- 26303036
TI  - Association of 3 Common Polymorphisms of IL-27 Gene with Susceptibility to Cancer
      in Chinese: Evidence From an Updated Meta-Analysis of 27 Studies.
AB  - BACKGROUND: Many epidemiology studies have indicated that several functional
      polymorphisms of the IL-27 gene may contribute to individual susceptibility to
      cancer. Nevertheless, the data arising from these studies were inconclusive.
      Therefore, we conducted the current meta-analysis aiming to elucidate the effects
      of IL-27 polymorphisms (rs153109, rs17855750, and rs181206) on cancer
      susceptibility. MATERIAL AND METHODS: We searched the CNKI (Chinese National
      Knowledge Infrastructure), Wanfang database, PubMed, Web of Science, and Google
      Scholar for all eligible publications. We used odds ratios (ORs) corresponding
      with 95% confidence intervals (CIs) by using the random/fixed-effects model to
      evaluate the association. Finally, a total of 12 publications, including 27 case
      control studies comprising of 7570 patients and 9839 controls, were enrolled in
      our meta-analysis. RESULTS: Our work demonstrates that IL-27 rs17855750
      polymorphism is significantly associated with cancer susceptibility, particularly
      for bladder cancer. However, no association between IL-27 rs153109 and rs181206
      polymorphisms and cancer susceptibility was identified. When a stratification
      analysis was performed by cancer type, we identified an increased susceptibility
      of bladder cancer in rs153109 polymorphism. Moreover, in the stratification
      analysis by genotyping method, we identified an increased susceptibility for PCR
      RFLP group in rs17855750 polymorphism, whereas a decreased susceptibility was
      identified in rs153109 polymorphism. CONCLUSIONS: Our study shows that IL-27
      rs17855750 polymorphism is significantly associated with increased susceptibility
      to cancer in Chinese.

PMID- 26303038
TI  - Incidence of hip fracture in Brazil and the development of a FRAX model.
AB  - The Brazilian FRAX model is described and used to determine intervention
      thresholds for the treatment of osteoporosis. INTRODUCTION: A FRAX model for
      Brazil was released May 1, 2013. This paper describes the data used to develop
      the Brazilian FRAX((r)) model, illustrates its features and develops intervention
      thresholds. METHODS: Age- and sex-stratified hip fracture incidence rates were
      extracted from four regional estimates from the age of 40 years. For other major
      fractures, Brazilian incidence rates were estimated using Swedish ratios for hip
      to other major osteoporotic fracture (humerus, forearm or clinical vertebral
      fractures). Assessment and intervention thresholds were determined using the
      approach recommended by the National Osteoporosis Guideline Group (UK) applied to
      the Brazilian FRAX model. RESULTS: Fracture incidence rates increased with
      increasing age: for hip fracture, incidence rates were higher amongst younger men
      than women but with a female preponderance from the age of 50 years. Ten-year
      probability of hip or major fracture was increased in patients with a clinical
      risk factor, lower BMI, female gender, a higher age and a decreased BMD T-score.
      Of the clinical risk factors, prior fracture accounted for the greatest increase
      in 10-year fracture probability at younger ages while a parental hip fracture
      history was the strongest risk factor at ages 80-90 years. Age-dependent
      probability-based intervention thresholds were developed equivalent to women with
      a prior fragility fracture. CONCLUSIONS: The FRAX tool is the first to provide a
      country-specific fracture prediction model for Brazil. It is based on the
      original FRAX methodology, which has been externally validated in several
      independent cohorts. Despite some limitations, the strengths make the Brazilian
      FRAX tool a good candidate for implementation into clinical practice.

PMID- 26303039
TI  - Gestational hypermethioninaemia alters oxidative/nitrative status in skeletal
      muscle and biomarkers of muscular injury and inflammation in serum of rat
      offspring.
AB  - In this study we evaluated oxidative/nitrative stress parameters (reactive oxygen
      species production, lipid peroxidation, sulfhydryl content, superoxide dismutase,
      catalase and nitrite levels), as well as total protein content in the
      gastrocnemius skeletal muscle of the offspring of rats that had been subjected to
      gestational hypermethioninaemia. The occurrence of muscular injury and
      inflammation was also measured by creatine kinase activity, levels of creatinine,
      urea and C-reactive protein and the presence of cardiac troponin I in serum.
      Wistar female rats (70-90 days of age) received methionine (2.68 MUmol/g body
      weight) or saline (control) twice a day by subcutaneous injections during the
      gestational period (21 days). After the rats gave birth, pups were killed at the
      twenty-first day of life for removal of muscle and serum. Methionine treatment
      increased reactive oxygen species production and lipid peroxidation and decreased
      sulfhydryl content, antioxidant enzymes activities and nitrite levels, as well as
      total protein content in skeletal muscle of the offspring. Creatine kinase
      activity was reduced and urea and C-reactive protein levels were increased in
      serum of pups. These results were accompanied by reduced muscle mass. Our
      findings showed that maternal gestational hypermethioninaemia induced changes in
      oxidative/nitrative status in gastrocnemius skeletal muscle of the offspring.
      This may represent a mechanism which can contribute to the myopathies and loss of
      muscular mass that is found in some hypermethioninaemic patients. In addition, we
      believe that these results may be relevant as gestational hypermethioninaemia
      could cause damage to the skeletal muscle during intrauterine life. 

PMID- 26303040
TI  - Undibacterium aquatile sp. nov., isolated from a waterfall.
AB  - A Gram-stain-negative, aerobic, motile and rod-shaped strain, THG-DN7.3T, was
      isolated from a waterfall. Strain THG-DN7.3T grew well at 18-28  degrees C and at
      pH 6.0-7.5 on Reasoner's 2A agar. Based on 16S rRNA gene sequence comparisons,
      strain THG-DN7.3T was most closely related to Undibacterium jejuense JS4-4T (97.3
      % 16S rRNA gene sequence similarity) and Undibacterium seohonense SHS5-24T (96.5
      %). The G+C content of the genomic DNA was 57.4 mol%. The mean DNA-DNA
      relatedness of strain THG-DN7.3T with U. jejuense KACC 12607T was 40 +/- 1 %
      (reciprocal 50 +/- 2.1 %). The major cellular fatty acids of strain THG-DN7.3T
      were summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c) (47.4 %), C16 : 0
      (30.4 %), summed feature 8 (C18 : 1omega6c and/or C18 : 1omega7c) (6.8 %) and C12
      : 0 (6.2 %). The predominant isoprenoid quinone was ubiquinone-8. The major polar
      lipids were phosphatidylethanolamine, phosphatidylglycerol and
      diphosphatidylglycerol. The results of the DNA-DNA hybridization and genotypic
      analysis, in combination with chemotaxonomic and physiological data, demonstrated
      that strain THG-DN7.3T represents a novel species of the genus Undibacterium, for
      which the name Undibacterium aquatile sp. nov. is proposed. The type strain is
      THG-DN7.3T ( = KCTC 42243T = CCTCC AB 2015119T).

PMID- 26303041
TI  - Iatrogenic metastasis of a colloid cyst.

PMID- 26303042
TI  - Peptidome profiling of venom from the social wasp Polybia paulista.
AB  - Most crude venom from Polybia paulista is composed of short, linear peptides;
      however, only five of these peptides are structurally and functionally
      characterized. Therefore, the peptides in this venom were profiled using an HPLC
      IT-TOF/MS and MS(n) system. The presence of type -d and -w ions that are
      generated from the fragmentation of the side chains was used to resolve I/L
      ambiguity. The distinction between K and Q residues was achieved through
      esterification of the alpha- and epsilon-amino groups in the peptide chains,
      followed by mass spectrometry analysis. Fourteen major peptides were detected in
      P. paulista venom and sequenced; all the peptides were synthesized on solid-phase
      and submitted to a series of bioassays. Five of them had been previously
      characterized, and nine were novel toxins. The novel peptides correspond to two
      wasp kinins, two chemotactic components, three mastoparans, and two peptides of
      unknown function. The seven novel peptides with identified functions appear to
      act synergistically with the previously known ones, constituting three well-known
      families of peptide toxins (wasp kinins, chemotactic peptides, and mastoparans)
      in the venom of social wasps. These multifunctional toxins can cause pain, oedema
      formation, haemolysis, chemotaxis of PMNLs, and mast cell degranulation in
      victims who are stung by wasps. 

PMID- 26303043
TI  - Serologic detection of antibodies against Fasciola hepatica in sheep in the
      middle Black Sea region of Turkey.
AB  - BACKGROUND/PURPOSE: The aim of the present study was to estimate the prevalence
      of Fasciola hepatica infection in sheep in the Black Sea region of Turkey.
      METHODS: Samples from 213 sheep were collected randomly in Samsun, Tokat, and
      Sinop from September 2005 to January 2007 and tested by indirect enzyme-linked
      immunosorbent assay (ELISA) and Western blot analysis using F. hepatica excretory
      secretory (E/S) antigens. RESULTS: The distribution of ELISA-positive samples for
      F. hepatica infections out of a total of 213 sheep serum samples was 23/71
      (32.4%), 15/59 (25.4%), and 29/83 (34.9%) in Samsun, Sinop, and Tokat,
      respectively. The immunodominant proteins were determined by Western blot
      analysis using molecular weight markers of 14 kDa, 20 kDa, 24 kDa, 27 kDa, 33
      kDa, 45 kDa, and 66 kDa and extracted from sera of sheep that were positive for
      Fasciola spp. eggs and also hyperimmune sera from rabbits immunized with E/S
      antigens. CONCLUSION: The ELISA-positive results were confirmed by Western blot
      analysis. As a result, seroprevalence of F. hepatica infection was found in 31.4%
      of sheep from the Karayaka breed in the Middle Black sea region of Turkey.

PMID- 26303044
TI  - RNA polymerase B subunit gene mutations in biofilm-embedded methicillin-resistant
      Staphylococcus aureus following rifampin treatment.
AB  - BACKGROUND/PURPOSE: This study was conducted to compare the mutation rates of
      different rpoB sites and rifampin minimum inhibitory concentration (MIC) changes
      prior to and after rifampin therapy for biofilm-embedded methicillin-resistant
      Staphylococcus aureus (MRSA) isolates. METHODS: The screening of rifampin
      resistant MRSA isolates, from the biofilm at Day 5 with or without exposure to
      the susceptible breakpoint concentration of rifampin recommended by the Clinical
      and Laboratory Standards Institute (1 mg/L), was conducted using agar plates
      containing rifampin. A partial fragment of RNA polymerase B subunit gene (rpoB),
      including clusters I and II, was amplified and sequenced. The rifampin MIC values
      and mutation frequencies at different sites of rpoB were measured and evaluated
      in rifampicin-resistant isolates. RESULTS: Rifampin-resistant mutants could be
      selected from all of 39 randomly selected rifampin-susceptible MRSA isolates in
      the biofilm model. The spontaneous mutation frequency ranged from 1.00 * 10(-4)
      to 3.85 * 10(-7). Mutation at codon 481 was most commonly found at 35 (89.7%) of
      39 MRSA isolates. Without rifampin induction, the MIC ranged between 0.125 mg/L
      and1024 mg/L and mutation sites included cluster I 464, 466, 468, 471, 474, 477,
      481, 484, 486 and cluster II 519, 527, 529 with the percentage of 471 (35.9%),
      477 (33.3%), 481 (53.8%), and 484 (35.9%). Conversely, with the induction of
      rifampin, the MIC value ranged ~256-1024 mg/L. The mutation sites that were more
      concentrated included 468 (17.9%), 477 (30.8%), 481 (89.7%), 484 (17.9%), and 486
      (33.3%). CONCLUSION: We documented high rifampin resistance induction activity
      when MRSA was engaged in biofilm with rifampin exposure. Monotherapy seems to be
      inadequate for MRSA in biofilm. There is an urgent need for developing effective
      combination therapies with less rifampin resistance-inducing activities for
      treating MRSA in biofilms.

PMID- 26303045
TI  - Exploiting AT2R to Improve CD117 Stem Cell Function In Vitro and In Vivo-
      Perspectives for Cardiac Stem Cell Therapy.
AB  - BACKGROUND/AIMS: CD117(+) stem cell (SC) based therapy is considered an
      alternative therapeutic option for terminal heart disease. However, controversies
      exist on the effects of CD117(+) SC implantation. In particular, the link between
      CD117(+) SC function and angiotensin-II-type-2 receptor (AT2R) after MI is
      continuously discussed. We therefore asked whether 1) AT2R stimulation influences
      CD117(+) SC properties in vitro and, 2) which effects can be ascribed to AT2R
      stimulation in vivo. METHODS: We approached AT2R stimulation with Angiotensin II
      while simultaneously blocking its opponent receptor AT1 with Losartan. CD117
      effects were dissected using a 2D-Matrigel assay and HL-1 co-culture in vitro. A
      model of myocardial infarction, in which we implanted EGFP(+) CD117 SC, was
      further applied. RESULTS: While we found indications for AT2R driven
      vasculogenesis in vitro, co-culture experiments revealed that CD117(+) SC improve
      vitality of cardiomyocytes independently of AT2R function. Likewise, untreated
      CD117(+) SC had a positive effect on cardiac function and acted cardioprotective
      in vivo. CONCLUSIONS: Therefore, our data show that transient AT2R stimulation
      does not significantly add to the beneficial actions of CD117(+) SC in vivo. Yet,
      exploiting AT2R driven vasculogenis via an optimized AT2R stimulation protocol
      may become a promising tool for cardiac SC therapy.

PMID- 26303046
TI  - Antibody-enhanced dengue disease generates a marked CNS inflammatory response in
      the black-tufted marmoset Callithrix penicillata.
AB  - Severe dengue disease is often associated with long-term neurological
      impairments, but it is unclear what mechanisms are associated with neurological
      sequelae. Previously, we demonstrated antibody-enhanced dengue disease (ADE)
      dengue in an immunocompetent mouse model with a dengue virus 2 (DENV2) antibody
      injection followed by DENV3 virus infection. Here we migrated this ADE model to
      Callithrix penicillata. To mimic human multiple infections of endemic zones where
      abundant vectors and multiple serotypes co-exist, three animals received weekly
      subcutaneous injections of DENV3 (genotype III)-infected supernatant of C6/36
      cell cultures, followed 24 h later by anti-DENV2 antibody for 12 weeks. There
      were six control animals, two of which received weekly anti-DENV2 antibodies, and
      four further animals received no injections. After multiple infections, brain,
      liver, and spleen samples were collected and tissue was immunolabeled for DENV3
      antigens, ionized calcium binding adapter molecule 1, Ki-67, TNFalpha. There were
      marked morphological changes in the microglial population of ADE monkeys
      characterized by more highly ramified microglial processes, higher numbers of
      trees and larger surface areas. These changes were associated with intense
      TNFalpha-positive immunolabeling. It is unclear why ADE should generate such
      microglial activation given that IgG does not cross the blood-brain barrier, but
      this study reveals that in ADE dengue therapy targeting the CNS host response is
      likely to be important. 

PMID- 26303047
TI  - Patients with refractory reflux symptoms: What do they have and how should they
      be managed?
AB  - With the widespread use of proton pump inhibitors (PPIs), the frontier of
      treating reflux disease has shifted from refractory esophagitis to PPI-refractory
      symptoms. However, symptoms are inherently less specific than mucosal disease
      and, as noted by Herregods et al. in their contribution appearing in this issue
      of Neurogastroenterology and Motility, patients with refractory gastroesophageal
      reflux disease (GERD) symptoms often do not have GERD. This review discusses
      potential etiologies for PPI-refractory symptoms. Three major concepts are
      explored: subendoscopic esophagitis, weakly acidic reflux events, and alternative
      explanations for persistent symptoms. With respect to subendoscopic esophagitis
      and unsuppressed reflux, ample evidence exists that these are present in PPI
      refractory patients. The problem is that these findings are also often present in
      substantial numbers of individuals with a satisfactory response to PPI therapy.
      Hence, the emphasis shifts to determinants of symptom perception. The major
      conclusion of the review is that psychogenic factors such as hyperalgesia,
      allodynia, hypervigilance, and heightened anxiety are the most plausible
      explanations as the dominant determinants of PPI-refractory symptoms. 

PMID- 26303048
TI  - Effect of 5-hydroxytryptamine receptor 4 agonist mosapride on human gastric
      accommodation.
AB  - BACKGROUND: Impaired gastric accommodation is one of the major features of
      functional dyspepsia. Mosapride citrate is a 5-hydroxytryptamine receptor 4 (5
      HT4) agonist, which is shown to improve upper abdominal symptoms. However, effect
      of mosapride on gastric accommodation was not clear. We tested the hypothesis
      that mosapride enhances the gastric accommodation in normal individuals. METHODS:
      Fourteen male healthy volunteers completed this study. Single administration of
      mosapride or placebo was performed randomly with more than 1-week interval.
      Subjects swallowed a triple-lumen polyvinyl tube with a polyethylene bag. The bag
      was positioned in the proximal stomach and the minimal distending pressure (MDP)
      was determined. The ramp distension starting from the MDP was then performed and
      subjects were instructed to score their perception using ordinate scales. Next
      the intra-bag pressure was set at MDP + 2 mmHg and a liquid meal was administered
      30 min later, and the intra-bag volume was recorded for 60 min. We compared the
      MDP, perception scores, and the intra-bag volume changes by administering placebo
      and mosapride. KEY RESULTS: Minimal distending pressure was not significantly
      different in subjects receiving mosapride or placebo. Treatment with mosapride
      had no effect on intra-bag pressures or volumes inducing first sensation or
      discomfort. Gastric accommodation, expressed as the difference between pre- and
      postmeal intra-bag volumes, and the percent change of the intra-bag volumes by
      the meal was significantly enhanced by mosapride compared with placebo.
      CONCLUSIONS & INFERENCES: This is the first study clearly demonstrating that
      single administration of 5-HT4 agonist can enhance gastric accommodation in
      humans. (Umin.ac.jp, number UMIN000014063).

PMID- 26303050
TI  - Erratum.

PMID- 26303049
TI  - Slow wave dysrhythmias in the diabetic small intestine.

PMID- 26303051
TI  - Endothelium-dependent vasodilation is related to the occurrence of cortical brain
      infarcts at MR imaging: The Prospective Investigation of the Vasculature in
      Uppsala Seniors (PIVUS) study.
AB  - BACKGROUND: Infarcts in the brain can be divided into larger cortical and smaller
      deep lacunar infarcts. The pathogenesis differs between these two types of
      infarctions. OBJECTIVE: This study aims to investigate the relationship between
      measures of endothelium-dependent vasodilation (EDV) and occurrence of cortical
      and lacunar infarcts in a population-based sample. METHODS: In the Prospective
      Study of the Vasculature in Uppsala Seniors (PIVUS) study, 1016 subjects aged 70
      were evaluated by the invasive forearm technique with acetylcholine (EDV) and
      brachial artery ultrasound to assess flow-mediated vasodilation (FMD). Six to
      seven years later MRI of the brain was performed, and the prevalence of cortical
      and lacunar infarcts was visually assessed in 407 randomly selected subjects.
      RESULTS: Lacunar infarcts were found in 22% and cortical infarcts in 5.9% of the
      subjects. EDV and FMD were both significantly related to the occurrence of
      cortical, but not lacunar infarcts. In a model adjusting for gender, waist
      circumference, body mass index, fasting blood glucose, systolic and diastolic
      blood pressure, HDL and LDL cholesterol, serum triglycerides, smoking,
      antihypertensive treatment and statin use, both EDV and FMD were independent
      predictors of cortical infarcts (P = 0.035 and P = 0.008, respectively).
      CONCLUSIONS: Endothelium-dependent vasodilation in both forearm resistance
      vessels and the brachial artery was related to the occurrence of cortical, but
      not lacunar, infarcts at MRI in a population-based sample independently of
      traditional risk factors.

PMID- 26303052
TI  - Association analysis of the GRN  rs5848 and MAPT rs242557 polymorphisms in
      Parkinson's disease and multiple system atrophy: a large-scale population-based
      study and meta-analysis.
AB  - BACKGROUND: Previous studies have found an association between the granulin gene
      rs5848 and microtubule-associated protein tau gene (MAPT) rs242557 polymorphisms
      and susceptibility to Parkinson's disease (PD). However, the results of
      association studies between the two polymorphisms and PD have been inconsistent.
      Given the overlap in clinical and pathological characteristics of PD and multiple
      system atrophy (MSA), we examined the associations of these two polymorphisms
      with PD and MSA in a subset of the Chinese population. METHODS: In total, 1270 PD
      patients, 360 MSA patients and 830 healthy controls (HCs) were included in the
      study. All subjects were genotyped for the two polymorphisms using Sequenom iPLEX
      Assay technology. After combining our results with the available published data,
      a meta-analysis was conducted to investigate the association between MAPT
      rs242557 and the risk of PD. RESULTS: The minor allele "T" of GRN rs5848
      decreased the risk for PD (p = 0.0309, odds radio [OR], 0.86; 95% CI, 0.76-0.99).
      No differences in the genotype distributions and minor allele frequency (MAF) of
      MAPT rs242557 were observed between the PD and the HCs in our Chinese population.
      Our meta-analysis revealed an association between MAPT rs242557 and PD in
      Caucasian and Asian population in a recessive model (p = 0.049 and p = 0.046,
      respectively). However, no significant differences in the genotype distributions
      and MAFs of the two polymorphisms were found between the MSA patients and HCs.
      CONCLUSION: Our results indicate that GRN rs5458 may decrease the risk of PD in
      Chinese individuals, and the MAPT rs242557 is marginally associated with PD.

PMID- 26303053
TI  - One-Pot Synthesis, Spectroscopic and Physicochemical Studies of Quinoline Based
      Blue Emitting Donor-Acceptor Chromophores with Their Biological Application.
AB  - Blue emitting cyano substituted isoquinoline dyes were synthesized by one-pot
      multicomponent reactions (MCRs) of aldehydes, malononitrile, 6-methoxy-1,2,3,4
      tetrahydro-naphthalin-1-one and ammonium acetate. Results obtained from
      spectroscopic (FT-IR, (1)H-NMR, (13)C-NMR, EI-MS) and elemental analysis of
      synthesized compounds was in good agreement with their chemical structures. UV
      vis and fluorescence spectroscopy measurements proved that all compounds are good
      absorbent and fluorescent. Fluorescence polarity study demonstrated that these
      compounds were sensitive to the polarity of the microenvironment provided by
      different solvents. In addition, spectroscopic and physicochemical parameters,
      including electronic absorption, excitation coefficient, stokes shift, oscillator
      strength, transition dipole moment and fluorescence quantum yield were
      investigated in order to explore the analytical potential of synthesized
      compounds. The anti-bacterial activity of these compounds were first studied in
      vitro by the disk diffusion assay against two Gram-positive and two Gram-negative
      bacteria then the minimum inhibitory concentration (MIC) was determined with the
      reference of standard drug chloramphenicol. The results displayed that compound 3
      was better inhibitors of both types of the bacteria (Gram-positive and Gram
      negative) than chloramphenicol. Graphical Abstract ?. 

PMID- 26303054
TI  - 'Through my eyes': health-promoting factors described by photographs taken by
      children with experience of cancer treatment.
AB  - BACKGROUND: Health promotion for children with cancer should be based on the
      children's own needs and desires. Because there is a lack of knowledge in this
      area, the aim of this study was to explore what promotes health from the
      perspective of children with experience of cancer treatment. METHODS: Fifteen
      children between 8 and 12 years of age participated in focus groups with three
      children in each group. The children were given a camera and instructions to
      photograph subjects that promote their health. Focus group discussions were based
      on the photographs and the children's own description of those photographs. The
      analysis of focus group discussions and photographs was conducted using inductive
      content analysis. RESULTS: According to the children, health-promoting factors
      are defined as meaningful relationships, recreational activities and a trustful
      environment. Meaningful relationships include togetherness within the family,
      affection for pets and friendship with peers. Recreational activities include
      engagement in play and leisure, withdrawal for relaxation and feeling enjoyment.
      Trustful environment includes confidence in significant others and feeling safe.
      CONCLUSIONS: Knowledge from this study can contribute to health promotion
      interventions and quality improvements in the health care of children with
      experience of cancer treatment. Children's experiences with what promotes health
      in their everyday lives provide a better understanding of the type of support
      children prefer when promoting their own health.

PMID- 26303055
TI  - Sequential population study of the impact of earthquakes on the emotional and
      behavioural well-being of 4-year-olds in Canterbury, New Zealand.
AB  - AIM: Exposure to a large natural disaster can lead to behavioural disturbances,
      developmental delay and anxiety among young children. Although most children are
      resilient, some will develop mental health problems. Major earthquakes occurred
      in Canterbury, New Zealand, in September 2010 and February 2011. A community
      screening tool assessing behavioural and emotional problems in children, the
      Strengths and Difficulties Questionnaire, has been reported by parents (SDQ-P)
      and teachers (SDQ-T) of all 4-year-olds in the region since 2008. METHODS: Mean
      total and subtest scores for the SDQ-P and SDQ-T were compared across periods
      before, during and after the earthquakes in sequential population cohorts of
      children. Comparisons across the periods were made in relation to the proportions
      of children defined by New Zealand norms as 'abnormal'. Results were also
      compared between zones considered to have been exposed to higher or lower impact
      from the earthquakes. RESULTS: Parent mean total SDQ scores did not change
      between periods before, during and after the earthquakes. Teacher mean SDQ total
      scores significantly reduced (improved) when compared between baseline and post
      earthquake periods. Mean SDQ pro-social scores from both teachers and parents
      increased (strengthened) when compared between baseline and post-earthquake
      periods. Results did not significantly vary according to a measure of impact from
      the earthquakes. CONCLUSION: The main finding that a population-based measure of
      behavioural and emotional problems among children was not deleteriously impacted
      by the earthquakes is surprising and is not consistent with other research
      findings. Further work is needed to explore the health needs of children in
      Canterbury based on methodological improvements.

PMID- 26303056
TI  - Determination of HLA-G Expression and Evaluation of Its Role as a Prognostic
      Factor in Chronic Lymphocytic Leukemia.
AB  - BACKGROUND: In recent years, the clinical and biological features governing the
      clinical course of chronic lymphocytic leukemia (CLL) have been most extensively
      studied. Human leukocyte antigen-G (HLA-G) allows tumor cells to escape from the
      antitumor effect of the immune system. Recent studies have shown that various
      tumor cells show an increased HLA-G expression. Data regarding HLA-G expression
      in CLL are limited and controversial. The aim of this work is to evaluate flow
      cytometry study of HLA-G expression on cell surface and assess its relationship
      with other prognostic factors (CD38, ZAP70, beta 2 microglobulin [beta2MG]) in
      patients with CLL. DESIGN AND METHODS: Forty-five newly diagnosed CLL cases.
      White blood cell count, lymphocyte absolute count, hemoglobin level, platelet
      count, serum lactate dehydrogenase activity, and serum beta2MG level were studied
      at admission. In each patient, morphologic diagnosis of B-CLL was confirmed by
      flow cytometry HLA-G, CD38 and ZAP70 expression levels were measured with four
      color flow cytometry. RESULTS: HLA-G positivity ranged between 1% and 12% in CLL
      patients. A significant correlation was found with CD38, ZAP70, disease stage,
      and beta2MG (P < 0.001). The off-treatment follow-up period was longer in the HLA
      G negative group (P < 0.022). CONCLUSIONS: In conclusion, we suggest that, in
      addition to other prognostic factors, surface HLA-G expression can be considered
      as an independent prognostic factor. However, our work should be confirmed by
      further prospective studies, a longer off-treatment follow-up period, and a
      standardized method.

PMID- 26303058
TI  - Caffeic Acid Inhibits UVB-induced Inflammation and Photocarcinogenesis Through
      Activation of Peroxisome Proliferator-activated Receptor-gamma in Mouse Skin.
AB  - In this study, the effect of caffeic acid (CA) on both acute and chronic UVB
      irradiation-induced inflammation and photocarcinogenesis was investigated in
      Swiss albino mice. Animals were exposed to 180 mJ cm(-2) of UVB once daily for 10
      consecutive days and thrice weekly for 30 weeks for acute and chronic study
      respectively. UVB exposure for 10 consecutive days showed edema formation,
      increased lipid peroxidation and decreased antioxidant status with activation of
      inflammatory molecules such as TNF-alpha, IL-6, COX-2 and NF-kappaB. However, CA
      (15 mg per kg.b.wt.) administration before each UVB exposure decreased lipid
      peroxidation, inflammatory markers expression and enhanced antioxidant status
      probably through the activation of peroxisome proliferator-activated receptors
      (PPARgamma) in the mice skin. PPARgamma is considered a potential target for
      photochemoprevention because it inhibits UVB-mediated inflammatory responses. In
      this study, UVB exposure for 30 weeks caused squamous cell carcinoma and
      upregulation of iNOS, VEGF and TGF-beta and downregulation of p53 and tumor
      incidence in the mice skin. Both topical (CAT) and intraperitoneal (CAIP)
      treatment before each UVB exposure downregulates iNOS, VEGF, TGF-beta,
      upregulates p53 and reduces tumors multiplicity in the mice skin. Thus, CA offers
      protection against UVB-induced photocarcinogenesis probably through activation of
      anti-inflammatory transcription factor PPARgamma in the mice. 

PMID- 26303057
TI  - Equity improvements in maternal and newborn care indicators: results from the
      Bardiya district of Nepal.
AB  - Community-based maternal and newborn care interventions have been shown to
      improve neonatal survival and other key health indicators. It is important to
      evaluate whether the improvement in health indicators is accompanied by a
      parallel increase in the equitable distribution of the intervention activities,
      and the uptake of healthy newborn care practices. We present an analysis of
      equity improvements after the implementation of a Community Based Newborn Care
      Package (CB-NCP) in the Bardiya district of Nepal. The package was implemented
      alongside other programs that were already in place within the district. We
      present changes in concentration indices (CIndices) as measures of changes in
      equity, as well as percentage changes in coverage, between baseline and endline.
      The CIndices were derived from wealth scores that were based on household assets,
      and they were compared usingt-tests. We observed statistically significant
      improvements in equity for facility delivery [CIndex: -0.15 (-0.24, -0.06)],
      knowledge of at least three newborn danger signs [-0.026(-0.06, -0.003)],
      breastfeeding within 1 h [-0.05(-0.11, -0.0001)], at least one antenatal visit
      with a skilled provider [-0.25(-0.04, -0.01)], at least four antenatal visits
      from any provider [-0.15(-0.19, -0.10)] and birth preparedness [-0.09(-0.12, 
      0.06)]. The largest increases in practices were observed for facility delivery
      (50%), immediate drying (34%) and delayed bathing (29%). These results and those
      of similar studies are evidence that community-based interventions delivered by
      female community health volunteers can be instrumental in improving equity in
      levels of facility delivery and other newborn care behaviours. We recommend that
      equity be evaluated in other similar settings within Nepal in order to determine
      if similar results are observed. 

PMID- 26303059
TI  - Single-Scan Multidimensional NMR Analysis of Mixtures at Sub-Millimolar
      Concentrations by using SABRE Hyperpolarization.
AB  - Signal amplification by reversible exchange (SABRE) is a promising method to
      increase the sensitivity of nuclear magnetic resonance (NMR) experiments.
      However, SABRE-enhanced (1)H NMR signals are short lived, and SABRE is often used
      to record 1D NMR spectra only. When the sample of interest is a complex mixture,
      this results in severe overlaps for (1)H spectra. In addition, the use of a co
      substrate, whose signals may obscure the (1) H spectra, is currently the most
      efficient way to lower the detection limit of SABRE experiments. Here, we
      describe an approach to obtain clean, SABRE-hyperpolarized 2D (1)H NMR spectra of
      mixtures of small molecules at sub-millimolar concentrations in a single scan.
      The method relies on the use of para-hydrogen together with a deuterated co
      substrate for hyperpolarization and ultrafast 2D NMR for acquisition. It is
      applicable to all substrates that can be polarized with SABRE.

PMID- 26303061
TI  - Stroke in atrial fibrillation and improving the identification of 'high-risk'
      patients: the crossroads of immunity and thrombosis.

PMID- 26303062
TI  - Action is needed to boost uptake of stop smoking services, say campaigners.

PMID- 26303064
TI  - Managing preconceived expectations: mental health service users experiences of
      going home from hospital: a grounded theory study.
AB  - ACCESSIBLE SUMMARY: What is known on the subject? The time of discharge from a
      mental health hospital can be challenging for mental health service users, with
      high rates of readmission in the immediate months following discharge. Although
      some research exists that explores service users' perspectives of being
      discharged, little evidence exists that explores the processes influencing or
      used by service users' to adapt to the transition from in-patient acute mental
      health service. What this papers adds to existing knowledge? The findings of this
      grounded theory study demonstrates the strategies service users used to managed
      their own, as well as their social audiences, preconceived expectations arising
      from their new identity as 'psychiatric patients' following their discharge from
      hospital. While there is a move to develop recovery-orientated mental health
      services, key indicators of recovery-oriented practices were often absent from
      service users' experiences of service provision. What are the implications for
      practice? Nurses and other mental health professionals need to recognize their
      contribution to the architecture of stigma that transcends the physical
      structures of hospital or ward and are entrenched within attitudes, interactions
      and practices. The findings of this study can provide guidance to those working
      with service users and help them to understand the complexities of their
      experiences when using mental health services, which go far beyond the management
      of their symptoms. ABSTRACT:  INTRODUCTION: Following a period of
      hospitalization, the transition to home can result in increased vulnerability and
      a source of stress for mental health service users. Readmission rates have been
      suggested as one indicator of the success of the transition from hospital to
      community care. Despite knowledge of some of the factors that impact on service
      users following discharge, no coherent model or theoretical framework could be
      located in the literature, which explains or aides an in-depth understanding of
      the transition from hospital to community for service users. AIM: The aim of this
      study was to develop a grounded theory that explored service users' experiences
      of going home from hospital. METHOD: This qualitative study used grounded theory,
      and a total of 35 interviews were conducted with 31 service users. RESULTS: The
      core category was 'Managing Preconceived Expectations', which had seven
      subcategories, describes how the participants were negatively perceived by
      themselves and others following their admission and discharge from hospital.
      IMPLICATIONS FOR PRACTICE: This theory presents the strategies that the
      participants used to manage this new identity. This theory demonstrates that
      although there has been a move to adopt recovery-orientated services, key
      indicators of recovery were often absent for service users being admitted and
      subsequently discharged.

PMID- 26303063
TI  - Vagal Recovery From Cognitive Challenge Moderates Age-Related Deficits in
      Executive Functioning.
AB  - Decline in executive functioning (EF) is a hallmark of cognitive aging. We have
      previously reported that faster vagal recovery from cognitive challenge is
      associated with better EF. This study examined the association between vagal
      recovery from cognitive challenge and age-related differences in EF among 817
      participants in the Midlife in the U.S. study (aged 35-86). Cardiac vagal control
      was measured as high-frequency heart rate variability. Vagal recovery moderated
      the association between age and EF (beta = .811, p = .004). Secondary analyses
      revealed that older participants (aged 65-86) with faster vagal recovery had
      superior EF compared to their peers who had slower vagal recovery. In contrast,
      among younger (aged 35-54) and middle-aged (aged 55-64) participants, vagal
      recovery was not associated with EF. We conclude that faster vagal recovery from
      cognitive challenge is associated with reduced deficits in EF among older, but
      not younger individuals.

PMID- 26303065
TI  - Up-regulation of c-Jun NH2-terminal kinase-interacting protein 3 (JIP3)
      contributes to BDNF-enhanced neurotransmitter release.
AB  - Brain-derived neurotrophic factor (BDNF) has been implicated in the potent
      modulation of synaptic plasticity at both pre-synaptic and post-synaptic sites.
      However, the molecular mechanism underlying BDNF-mediated pre-synaptic modulation
      remains incompletely understood. Here, we report that BDNF treatment for over 4 h
      could significantly enhance the expression of c-Jun NH2-terminal kinase
      interacting protein 3 (JIP3) in cultured hippocampal neurons. This enhancement
      could be blocked by the Trk inhibitor K252a or by a cAMP response element-binding
      protein (CREB) inhibitor. In addition, chromatin immunoprecipitation (ChIP)
      assays revealed that CREB could bind with the JIP3 promoter region and the BDNF
      treatment could increase this binding. Using dual-luciferase assays we further
      characterized the cAMP response element (CRE) site in the JIP3 promoter. Finally,
      we found that BDNF-increased JIP3 expression contributes to the BDNF-induced
      modulation of neurotransmitter release. Together, our studies reveal that in
      hippocampal neurons BDNF up-regulates JIP3 expression via CREB activation, which
      contributes to the enhancement of neurotransmitter release; thus, we have
      identified a novel mechanism that BDNF modulates pre-synaptic transmission.

PMID- 26303066
TI  - MRC special issue on fast multi-dimensional NMR methods.

PMID- 26303067
TI  - Essential Role of X-Box Binding Protein-1 during Endoplasmic Reticulum Stress in
      Podocytes.
AB  - Podocytes are terminally differentiated epithelial cells that reside along the
      glomerular filtration barrier. Evidence suggests that after podocyte injury,
      endoplasmic reticulum stress response is activated, but the molecular mechanisms
      involved are incompletely defined. In a mouse model, we confirmed that podocyte
      injury induces endoplasmic reticulum stress response and upregulated unfolded
      protein response pathways, which have been shown to mitigate damage by preventing
      the accumulation of misfolded proteins in the endoplasmic reticulum. Furthermore,
      simultaneous podocyte-specific genetic inactivation of X-box binding protein-1
      (Xbp1), a transcription factor activated during endoplasmic reticulum stress and
      critically involved in the untranslated protein response, and Sec63, a heat shock
      protein-40 chaperone required for protein folding in the endoplasmic reticulum,
      resulted in progressive albuminuria, foot process effacement, and histology
      consistent with ESRD. Finally, loss of both Sec63 and Xbp1 induced apoptosis in
      podocytes, which associated with activation of the JNK pathway. Collectively, our
      results indicate that an intact Xbp1 pathway operating to mitigate stress in the
      endoplasmic reticulum is essential for the maintenance of a normal glomerular
      filtration barrier.

PMID- 26303068
TI  - Three-Dimensional Morphology by Multiphoton Microscopy with Clearing in a Model
      of Cisplatin-Induced CKD.
AB  - Traditional histologic methods are limited in their ability to detect pathologic
      changes of CKD, of which cisplatin therapy is an important cause. In addition,
      poor reproducibility of available methods has limited analysis of the role of
      fibrosis in CKD. Highly labor-intensive serial sectioning studies have
      demonstrated that three-dimensional perspective can reveal useful morphologic
      information on cisplatin-induced CKD. By applying the new technique of
      multiphoton microscopy (MPM) with clearing to a new mouse model of cisplatin
      induced CKD, we obtained detailed morphologic and collagen reconstructions of
      millimeter-thick renal sections that provided new insights into pathophysiology.
      Quantitative analysis revealed that a major long-term cisplatin effect is
      reduction in the number of cuboidal cells of the glomerular capsule, a change we
      term the "uncapped glomerulus lesion." Glomerulotubular disconnection was
      confirmed, but connection remnants between damaged tubules and atubular glomeruli
      were observed. Reductions in normal glomerular capsules corresponded to
      reductions in GFR. Mild increases in collagen were noted, but the fibrosis was
      not spatially correlated with atubular glomeruli. Glomerular volume and number
      remained unaltered with cisplatin exposure, but cortical tubulointerstitial mass
      decreased. In conclusion, new observations were made possible by using clearing
      MPM, demonstrating the utility of this technique for studies of renal disease.
      This technique should prove valuable for further characterizing the evolution of
      CKD with cisplatin therapy and of other conditions. 

PMID- 26303069
TI  - Clinical and Financial Impact of Ordering an Echocardiogram in Children with Left
      Axis Deviation on Their Electrocardiogram.
AB  - OBJECTIVE: Left axis deviation (LAD) on the electrocardiogram (ECG) is associated
      with congenital heart disease (CHD), prompting the clinician to order further
      testing when evaluating a patient with this finding. The purpose is to (1)
      compare the physical examination (PE) by a pediatric cardiologist to
      echocardiogram (ECHO) findings in patients with LAD on resting ECG and (2) assess
      cost of performing ECHO on all patients with LAD on ECG. DESIGN: An IRB approved,
      retrospective cohort study was performed on patients with LAD (QRS axis >=0
      degrees  to -90 degrees ) on ECG between 01/02 and 12/12. INCLUSION CRITERIA: age
      >0.25 and <18 years, non-postoperative, and PE and ECHO by pediatric
      cardiologist. A decision tree model analyzed cost of ECHO in patients with LAD
      and normal/abnormal PE. Cost of complete ECHO ($239.00) was obtained from 2014
      Medicare reimbursement rates. RESULTS: A total of 146 patients met inclusion
      criteria with 46.5% (68) having normal PE and ECHO, 1.4% (2) having normal PE and
      abnormal ECHO, 47.3% (69) having abnormal PE and ECHO, and 4.8% (7) having an
      abnormal PE and normal ECHO. Sensitivity and specificity of PE for detecting
      abnormalities in this population was 97% and 90%. Positive and negative
      predictive value of PE was 91% and 97.5%. In patients with normal PE, the cost to
      identify an ECHO abnormality was $8365, and $263 for those with abnormal PE.
      CONCLUSION: In presence of LAD on ECG, the sensitivity, specificity, and positive
      and negative predictive values of PE by a pediatric cardiologist are excellent at
      identifying CHD. Performing an ECHO on patients with LAD on ECG is only cost
      effective in the presence of an abnormal PE. In the presence of normal PE, there
      is a possibility of missing incidental structural cardiac disease in
      approximately 2% if an ECHO is not performed.

PMID- 26303070
TI  - Bcl3 Bridges LIF-STAT3 to Oct4 Signaling in the Maintenance of Naive
      Pluripotency.
AB  - Leukemia inhibitory factor (LIF) regulates mouse embryonic stem cell (mESC)
      pluripotency through STAT3 activation, but the downstream signaling remains
      largely unelucidated. Using cDNA microarrays, we verified B cell
      leukemia/lymphoma 3 (Bcl3) as the most significantly downregulated factor
      following LIF withdrawal in mESCs. Bcl3 knockdown altered mESC morphology,
      reduced expression of pluripotency genes including Oct4, Sox2, and Nanog, and
      downregulated DNA binding of acetylated histone 3 and RNA polymerase II on the
      Oct4 promoter. Conversely, Bcl3 overexpression partially prevented cell
      differentiation and promoted Oct4 and Nanog promoter activities. Furthermore,
      coimmunoprecipitation and chromatin immunoprecipitation experiments demonstrated
      that Bcl3 regulation of mESC pluripotency may be through its association with
      Oct4 and beta-catenin and its promoter binding capability. These results
      establish that Bcl3 positively regulates pluripotency genes and thus shed light
      on the mechanism of Bcl3 as a downstream molecule of LIF/STAT3 signaling in
      pluripotency maintenance.

PMID- 26303071
TI  - Pleural mass forming extramedullary hematopoiesis masquerading as a malignant
      neoplasm.
AB  - Extramedullary hematopoiesis (EMH) represents the presence of immature
      hematopoietic elements and their differentiation into mature blood components
      outside of the medullary bone and may be seen in a variety of circumstances in
      the postnatal period, but is most strongly associated with disorders of the
      hematopoietic system. Postnatally, EMH is typically identified at sites of fetal
      hematopoiesis, the spleen, and liver, but occasional reports have identified it
      in nearly every tissue of the body. We report a case of EMH presenting as pleural
      mass, initially suspected to represent a neoplastic process in a patient with
      multiple comorbidities, including history of carcinoma, but without co-existing
      hematologic disorder. On-site evaluation of the fine-needle aspiration specimen
      was initially suspicious for a malignant neoplasm, but further evaluation
      revealed the lesion to be a mass forming focus of non-hepatosplenic EMH. In the
      era of increasing utilization of imaging, mass forming EMH is increasingly
      detected. When unsuspected, EMH may present a diagnostic challenge for the
      pathologist and may be confused for a neoplastic process.

PMID- 26303072
TI  - Do people with spinal cord injury meet the WHO recommendations on physical
      activity?
AB  - OBJECTIVES: To describe physical activity (PA) levels in persons with spinal cord
      injury (SCI) and to investigate associated factors. METHODS: PA behavior of
      people with SCI in Switzerland was assessed in a community survey with four items
      from the Physical Activity Scale for individuals with physical disabilities (PA
      of light, moderate, and strenuous intensity and muscle-strengthening exercises).
      In addition to descriptive analyses, the odds of performing PA according to the
      WHO recommendations (at least 2.5 h/week of at least moderate intensity) were
      analyzed by multivariable logistic regression. RESULTS: Participants (n = 485;
      aged 52.9 +/- 14.8; 73.6 % male) carried out PA a total of 6.0 h/week (median).
      18.6 % were physically inactive, 50.3 % carried out muscle-strengthening
      exercises, and 48.9 % fulfilled the WHO recommendations. Regression analyses
      showed that women, people aged 71+, and people with complete tetraplegia had
      significantly lower odds of fulfilling the WHO recommendations than participants
      in the respective reference category (men, ages 17-30, incomplete paraplegia).
      CONCLUSIONS: PA levels of people with SCI in Switzerland are rather high.
      However, some subgroups need special consideration when planning interventions to
      increase PA levels.

PMID- 26303073
TI  - Unemployment, public-sector healthcare expenditure and colorectal cancer
      mortality in the European Union: 1990-2009.
AB  - OBJECTIVES: We examined the association between unemployment and government
      spending on healthcare with colorectal cancer mortality. METHODS: Retrospective
      observational study using data from the World Bank and WHO. Multivariate
      regression analysis was used, controlling for country-specific differences in
      infrastructure and demographics. RESULTS: A 1 % increase in unemployment was
      associated with a significant increase in colorectal cancer mortality in both men
      and women [men: coefficient (R) = 0.0995, 95 % confidence interval (CI) 0.0132
      0.1858, P = 0.024; women: R = 0.0742, 95 % CI 0.0160-0.1324, P = 0.013]. A 1 %
      increase in government spending on healthcare was associated with a statistically
      significant decrease in colorectal cancer mortality across both sexes (men: R = 
      0.4307, 95 % CI -0.6057 to -0.2557, P < 0.001; women: R = -0.2162, 95 % CI 
      0.3407 to -0.0917, P = 0.001). The largest changes in mortality occurred 3-4
      years following changes in either economic variable. CONCLUSIONS: Unemployment
      rises are associated with a significant increase in colorectal cancer mortality,
      whilst government healthcare spending rises are associated with falling
      mortality. This is likely due, in part, to reduced access to healthcare services
      and has major implications for clinicians and policy makers alike.

PMID- 26303074
TI  - Measuring the effect of ethnic and non-ethnic discrimination on Europeans' self
      rated health.
AB  - OBJECTIVES: The study of perceived discrimination based on race and ethnic traits
      belongs to a long-held tradition in this field, but recent studies have found
      that non-ethnic discrimination based on factors such as gender, disability or age
      is also a crucial predictor of health outcomes. METHODS: Using data from the
      European Social Survey (2010), and applying Boolean Factor Analysis and Ordered
      Logistic Regression models, this study is aimed to compare how ethnic and non
      ethnic types of discrimination might affect self-rated health in the European
      context. RESULTS: We found that non-ethnic types of discrimination produce
      stronger differences on health outcomes. This result indicates that the
      probabilities of presenting a poor state of health are significantly higher when
      individuals feel they are being discriminated against for social or demographic
      conditions (gender, age, sexuality or disability) rather than for ethnic reasons
      (nationality, race, ethnicity, language or religiosity). CONCLUSIONS: This study
      offers a clear comparison of health inequalities based on ethnic and non-ethnic
      types of discrimination in the European context, overcoming analytical based on
      binary indicators and simple measures of discrimination.

PMID- 26303075
TI  - Quantum Nonlocality of Arbitrary Dimensional Bipartite States.
AB  - We study the nonlocality of arbitrary dimensional bipartite quantum states. By
      computing the maximal violation of a set of multi-setting Bell inequalities, an
      analytical and computable lower bound has been derived for general two-qubit
      states. This bound gives the necessary condition that a two-qubit state admits no
      local hidden variable models. The lower bound is shown to be better than that
      from the CHSH inequality in judging the nonlocality of some quantum states. The
      results are generalized to the case of high dimensional quantum states, and a
      sufficient condition for detecting the non-locality has been presented. 

PMID- 26303076
TI  - A computational study of the phosphoryl transfer reaction between ATP and Dha in
      aqueous solution.
AB  - Phosphoryl transfer reactions are ubiquitous in biology, being involved in
      processes ranging from energy and signal transduction to the replication genetic
      material. Dihydroxyacetone phosphate (Dha-P), an intermediate of the synthesis of
      pyruvate and a very important building block in nature, can be generated by
      converting free dihydroxyacetone (Dha) through the action of the dihydroxyacetone
      kinase enzyme. In this paper the reference uncatalyzed reaction in solution has
      been studied in order to define the foundations of the chemical reaction and to
      determine the most adequate computational method to describe this electronically
      complex reaction. In particular, the phosphorylation reaction mechanism between
      adenosine triphosphate (ATP) and Dha in aqueous solution has been studied by
      means of quantum mechanics/molecular mechanics (QM/MM) Molecular Dynamics (MD)
      simulations with the QM subset of atoms described with semi-empirical and DFT
      methods. The results appear to be strongly dependent on the level of calculation,
      which will have to be taken into account for future studies of the reaction
      catalyzed by enzymes. In particular, PM3/MM renders lower free energy barriers
      and a less endergonic process than AM1d/MM and PM6/MM methods. Nevertheless, the
      concerted pathway was not located with the former combination of potentials. 

PMID- 26303077
TI  - Self-efficacy regarding physical activity is superior to self-assessed activity
      level, in long-term prediction of cardiovascular events in middle-aged men.
AB  - BACKGROUND: Self-efficacy has been determined to be a strong predictor of who
      will engage in physical activity. We aimed to evaluate the associations between
      self-efficacy to perform physical activity, self-reported leisure-time physical
      activity and cardiovascular events in a population-based cohort of middle-aged
      Swedish men with no previous cardiovascular disease, or treatment with
      cardiovascular drugs. METHODS: Analyses are based on 377 men randomly selected
      and stratified for weight and insulin sensitivity from a population sample of 58
      year-old men (n = 1728) and who had answered a question about their competence to
      perform exercise (as an assessment of physical self-efficacy). The Saltin-Grimby
      Physical Activity Level Scale was used to assess self-reported levels of leisure
      time physical activity. Cardiovascular events were recorded during 13-years of
      follow-up. RESULTS: The group with poor self-efficacy to perform physical
      activity had a significantly higher incidence of cardiovascular events compared
      with the group with good physical self-efficacy (32.1% vs 17.1%, p < 0.01).
      Multivariate analyses showed that poor physical self-efficacy was associated with
      an increased relative risk of 2.0 (95% CI 1.2 to 3.0), of having a cardiovascular
      event during follow-up also after adjustments for co-variates such as waist to
      hip ratio, heart rate, fasting plasma glucose, serum triglycerides, systolic
      blood pressure, apoB/apoA-I ratio and leisure-time physical activity. CONCLUSION:
      Self-efficacy to perform physical activity was strongly and independently
      associated with cardiovascular events and was superior to self-assessed physical
      activity in predicting cardiovascular events during 13-years of follow-up in a
      group of middle-aged men, without known CVD or treatment with cardiovascular
      drugs.

PMID- 26303078
TI  - Was Cajal right about sleep?
AB  - Cajal's careful observations of the anatomy of the nervous system led him to some
      lesser-known predictions about the function of glia as mediators of sleep.
      Reporting over 120 years later in BMC Biology, Bellesi et al. examine changes in
      gene expression and morphology of astrocytes with sleep. Their results provide
      support for and revisions to Cajal's predictions.See research article: doi:
      10.1186/s12915-015-0176-7 .

PMID- 26303079
TI  - Preface.

PMID- 26303080
TI  - Classical nuclear hormone receptor activity as a mediator of complex biological
      responses: a look at health and disease.
AB  - Nuclear hormone receptors are a large family of receptors that bind a wide range
      of lipolic hormones and intracellular ligands. They act as ligand-inducible
      transcription factors to regulate the expression of target genes and play
      important roles in normal development, reproduction, and metabolism. NRs bind to
      hormones steroids, thyroid hormone, and vitamin D as well as metabolites of fatty
      acids, cholesterol, and bild acids. Orphan receptors are another group of NRs for
      which no known ligands have been identified yet but appear to have major roles in
      regulating intracellular metabolism. Targeting NRs has been a major source for
      the development of new drugs, particularly selective agonists and antagonists for
      cancer and metabolic diseases. Additionally, hormone resistance syndromes in man
      have enlarged our understanding of the functions of specific NRs and their
      isoforms as well as genetic mechanisms for phenotype expression. 

PMID- 26303081
TI  - Noncoding RNAs and the control of signalling via nuclear receptor regulation in
      health and disease.
AB  - Nuclear receptors belong to a superfamily of proteins that play central roles in
      human biology, orchestrating a large variety of biological functions in both
      health and disease. Understanding the interactions and regulatory pathways of NRs
      will allow development of potential therapeutic interventions for a multitude of
      disease processes. Non-coding RNAs have recently been discovered to have
      significant interactions with NR signalling pathways via a variety of biological
      connections. This review summarises the known interactions between ncRNAs and the
      NR superfamily in health, embryogenesis and a plethora of human diseases. 

PMID- 26303083
TI  - Estrogen receptor alpha and beta in health and disease.
AB  - Estrogen receptors alpha (ERalpha) and beta (ERbeta) are transcription factors
      that are involved in the regulation of many complex physiological processes in
      humans. Abnormal ER signaling leads to development of a variety of diseases, such
      as cancer, metabolic and cardiovascular disease, neurodegeneration, inflammation,
      and osteoporosis. This review provides an overview and update on ERalpha and
      ERbeta in health and disease with focus on their role in cancer and metabolic
      disease and in the context of recent years' success in providing genome wide data
      on ER function. Furthermore, potential clinical applications and challenges are
      also discussed. 

PMID- 26303082
TI  - Specificity and sensitivity of glucocorticoid signaling in health and disease.
AB  - Endogenous glucocorticoids regulate a variety of physiologic processes and are
      crucial to the systemic stress response. Glucocorticoid receptors are expressed
      throughout the body, but there is considerable heterogeneity in glucocorticoid
      sensitivity and induced biological responses across tissues. The immunoregulatory
      properties of glucocorticoids are exploited in the clinic for the treatment of
      inflammatory and autoimmune disorders as well as certain hematological
      malignancies, but adverse side effects hamper prolonged use. Fully understanding
      the molecular events that shape the physiologic effects of glucocorticoid
      treatment will provide insight into optimal glucocorticoid therapies, reliable
      assessment of glucocorticoid sensitivity in patients, and may advance the
      development of novel GR agonists that exert immunosuppressive effects while
      avoiding harmful side effects. In this review, we provide an overview of
      mechanisms that affect glucocorticoid specificity and sensitivity in health and
      disease, focusing on the distinct isoforms of the glucocorticoid receptor and
      their unique regulatory and functional properties. 

PMID- 26303084
TI  - Androgen insensitivity syndrome.
AB  - Androgen insensitivity syndrome (AIS) results from androgen receptor dysfunction
      and is a common cause of disorder of sex development. The AIS phenotype largely
      depends on the degree of residual androgen receptor (AR) activity. This review
      describes the molecular action of androgens and the range of androgen receptor
      gene mutations, essential knowledge to understand the pathogenesis of the
      complete and partial forms of this syndrome. A multidisciplinary approach is
      recommended for clinical management from infancy through to adulthood. Hormone
      replacement therapy is needed following gonadectomy. Patients who choose to
      retain the gonads are at risk of developing germ cell tumors for which sensitive
      circulating tumor markers may soon become available. Whilst the contribution of
      AR dysfunction to complete AIS is well understood, the involvement of the AR and
      associated proteins as contributors to partial AIS is an area of active research.
      Disorders of sex development such as AIS which are related to AR dysfunction
      offer a breadth of manifestations for the clinician to manage and opportunities
      for further research on the mechanism of androgen action. 

PMID- 26303086
TI  - Androgen receptor roles in spermatogenesis and infertility.
AB  - Androgens such as testosterone are steroid hormones essential for normal male
      reproductive development and function. Mutations of androgen receptors (AR) are
      often found in patients with disorders of male reproductive development, and
      milder mutations may be responsible for some cases of male infertility. Androgens
      exert their action through AR and its signalling in the testis is essential for
      spermatogenesis. AR is not expressed in the developing germ cell lineage so is
      thought to exert its effects through testicular Sertoli and peri-tubular myoid
      (PTM) cells. AR signalling in spermatogenesis has been investigated in rodent
      models where testosterone levels are chemically supressed or models with
      transgenic disruption of AR. These models have pinpointed the steps of
      spermatogenesis that require AR signalling, specifically maintenance of
      spermatogonial numbers, blood-testis barrier integrity, completion of meiosis,
      adhesion of spermatids and spermiation, together these studies detail the
      essential nature of androgens in the promotion of male fertility. 

PMID- 26303085
TI  - Overlapping nongenomic and genomic actions of thyroid hormone and steroids.
AB  - The genomic actions of thyroid hormone and steroids depend upon primary
      interactions of the hormones with their specific nuclear receptor proteins.
      Formation of nuclear co-activator or co-repressor complexes involving the
      liganded receptors subsequently result in transcriptional events-either
      activation or suppression-at genes that are specific targets of thyroid hormone
      or steroids. Nongenomic actions of thyroid hormone and steroids are in contrast
      initiated at binding sites on the plasma membrane or in cytoplasm or organelles
      and do not primarily require formation of intranuclear receptor protein-hormone
      complexes. Importantly, hormonal actions that begin nongenomically outside the
      nucleus often culminate in changes in nuclear transcriptional events that are
      regulated by both traditional intranuclear receptors as well as other nuclear
      transcription factors. In the case of thyroid hormone, the extranuclear receptor
      can be the classical "nuclear" thyroid receptor (TR), a TR isoform, or integrin
      alphavbeta3. In the case of steroid hormones, the membrane receptor is usually,
      but not always, the classical "nuclear" steroid receptor. This concept defines
      the paradigm of overlapping nongenomic and genomic hormone mechanisms of action.
      Here we review some examples of how extranuclear signaling by thyroid hormone and
      by estrogens and androgens modulates intranuclear hormone signaling to regulate a
      number of vital biological processes both in normal physiology and in cancer
      progression. We also point out that nongenomic actions of thyroid hormone may
      mimic effects of estrogen in certain tumors. 

PMID- 26303088
TI  - Vitamin D signaling in calcium and bone homeostasis: a delicate balance.
AB  - Loss-of-function mutations in genes involved in the vitamin D/vitamin D receptor
      system have clearly evidenced its critical role for mineral and skeletal
      homeostasis. Adequate levels of 1,25-dihydroxyvitamin D [1,25(OH)2D], the active
      form of vitamin D are therefore required and depend on sufficient sunlight
      exposure or dietary intake. Intestinal calcium absorption is a primary target of
      1,25(OH)2D action and this pathway indirectly promotes calcium incorporation in
      bone. Severe vitamin D deficiency may thus decrease bone quality and leads to
      osteomalacia, whereas less severe deficiency increases the risk of osteoporosis
      and bone fractures. On the other hand, high vitamin D levels together with low
      dietary calcium intake will increase bone resorption and decrease bone
      mineralization in order to maintain normal serum calcium levels. Appropriate
      dietary calcium intake and sufficient serum vitamin D levels are thus important
      for skeletal health. Dosing of calcium and vitamin D supplements is still debated
      and requires further investigation. 

PMID- 26303087
TI  - DAX-1 (NR0B1) and steroidogenic factor-1 (SF-1, NR5A1) in human disease.
AB  - DAX-1 (NR0B1) and SF-1 (NR5A1) are two nuclear receptor transcription factors
      that play a key role in human adrenal and reproductive development. Loss of DAX-1
      function is classically associated with X-linked adrenal hypoplasia congenita.
      This condition typically affects boys and presents as primary adrenal
      insufficiency in early infancy or childhood, hypogonadotropic hypogonadism at
      puberty and impaired spermatogenesis. Late onset forms of this condition and
      variant phenotypes are increasingly recognized. In contrast, disruption of SF-1
      only rarely causes adrenal insufficiency, usually in combination with testicular
      dysgenesis. Variants in SF-1/NR5A1 more commonly cause a spectrum of reproductive
      phenotypes ranging from 46,XY DSD (partial testicular dysgenesis or reduced
      androgen production) and hypospadias to male factor infertility or primary
      ovarian insufficiency. Making a specific diagnosis of DAX-1 or SF-1 associated
      conditions is important for long-term monitoring of endocrine and reproductive
      function, appropriate genetic counselling for family members, and for providing
      appropriate informed support for young people. 

PMID- 26303089
TI  - Inherited forms of mineralocorticoid hypertension.
AB  - Aldosterone plays an essential role in the maintenance of fluid and electrolyte
      homeostasis in the distal nephron. Monogenic forms of mineralocorticoid
      hypertension result from genetic defects leading to excessive production of
      aldosterone (or other mineralocorticoids) from the adrenal cortex or to
      illegitimate mineralocorticoid effects in the kidney. They are characterized in
      the majority of cases by early onset, severe or resistant hypertension and
      associated with suppressed renin levels. Depending on their causes, these
      diseases are distinguished at the clinical and biochemical level and differently
      affect aldosterone levels and kalemia. The diagnosis is confirmed by genetic
      testing, which allows in many cases targeted treatment to prevent severe
      cardiovascular consequences of high blood pressure or aldosterone excess. In this
      review we describe the different forms of inherited mineralocorticoid
      hypertension, providing an overview of their clinical and biochemical features,
      their underlying genetic defects and specific therapeutic options. 

PMID- 26303090
TI  - Resistance to thyroid hormone due to defective thyroid receptor alpha.
AB  - Thyroid hormones act via nuclear receptors (TRalpha1, TRbeta1, TRbeta2) with
      differing tissue distribution; the role of alpha2 protein, derived from the same
      gene locus as TRalpha1, is unclear. Resistance to thyroid hormone alpha
      (RTHalpha) is characterised by tissue-specific hypothyroidism associated with
      near-normal thyroid function tests. Clinical features include dysmorphic facies,
      skeletal dysplasia (macrocephaly, epiphyseal dysgenesis), growth retardation,
      constipation, dyspraxia and intellectual deficit. Biochemical abnormalities
      include low/low-normal T4 and high/high-normal T3 concentrations, a subnormal
      T4/T3 ratio, variably reduced reverse T3, raised muscle creatine kinase and mild
      anaemia. The disorder is mediated by heterozygous, loss-of-function, mutations
      involving either TRalpha1 alone or both TRalpha1 and alpha2, with no discernible
      phenotype attributable to defective alpha2. Whole exome sequencing and diagnostic
      biomarkers may enable greater ascertainment of RTHalpha, which is important as
      thyroxine therapy reverses some metabolic abnormalities and improves growth,
      constipation, dyspraxia and wellbeing. The genetic and phenotypic heterogeneity
      of RTHalpha and its optimal management remain to be elucidated. 

PMID- 26303091
TI  - Neuro-nutraceuticals: The path to brain health via nourishment is not so distant.
AB  - In this Special Issue on "Nutraceuticals: Molecular and Functional Insights into
      how Natural Products Nourish the Brain", the editors bring together contributions
      from experts in nutraceutical research to provide a contemporary overview of how
      select chemically identified molecules can beneficially affect brain function at
      the molecular level. Other contributions address key emergent issues such as
      bioavailability, formulation, blood brain permeability, neuronal health and
      inflammation that impact upon how nutraceuticals ultimately leverage the brain to
      function better. Whilst nutraceutical is used as marketing term, it has no
      regulatory definition, and there is a continuing need for licensing authorities
      to ensure that adequate guidelines exist pertinent to the safety to guide
      consumers internationally. In terms of the benefit of nutraceuticals is it clear
      that some naturally occurring molecules can be advantageous to both the young and
      aged brain, and that they have actions that ultimately can be directed to aid
      either in the improvement of cognition or in the management of debilitating
      neurodegenerative and neuropsychiatric conditions. 

PMID- 26303092
TI  - Presence of PAHs in water and sediments of the Colombian Cauca River during heavy
      rain episodes, and implications for risk assessment.
AB  - In Colombia little attention has been paid to river pollution with Polycyclic
      Aromatic Hydrocarbons (PAHs). Low environmental control and legislation in such
      emerging region could significantly contribute to high PAHs releases. In this
      study, we report the presence of PAHs in water and sediments of the Cauca River
      (Colombia). Three sampling campaigns were carried out between May 2010 and June
      2011, and the samples were collected at eight relevant sites. The sampling time
      included measuring before, during, and after a season of heavy rains, which were
      influenced by the global coupled ocean-atmospheric phenomenon, which affected
      tropical countries with huge flooding, commonly called "La Nina", and/or "El
      Nino" Southern Oscillation (ENSO). The highest mean ?PAH concentrations were
      4476.5 ng/l and 1582.7 ng/g in water and sediments, respectively. The PAHs most
      detected were Benzo[b]fluoranthene, Benzo[k]fluoranthene, and Pyrene in
      sediments; and Fluorene, Acenaphtylene, and Anthracene in water. After the season
      of rains statistically significant higher PAH concentrations were detected. The
      results of the study were compared to other rivers worldwide at both
      environmental compartments, and did not show concentrations of special concern.
      In some sites, concentrations detected of PAHs were higher than screening
      benchmarks for ecological protection. Estimation of human health risks was
      carried out, and the results suggested some likely carcinogenic effects due to
      PAHs especially in children exposed during current recreational swimming and
      adults working in low technology sand extraction.

PMID- 26303093
TI  - Molecular characterization and development of Sarcocystis speeri sarcocysts in
      gamma interferon gene knockout mice.
AB  - The North American opossum (Didelphis virginiana) is the definitive host for at
      least three named species of Sarcocystis: Sarcocystis falcatula, Sarcocystis
      neurona and Sarcocystis speeri. The South American opossums (Didelphis
      albiventris, Didelphis marsupialis and Didelphis aurita) are definitive hosts for
      S. falcatula and S. lindsayi. The sporocysts of these Sarcocystis species are
      similar morphologically. They are also not easily distinguished genetically
      because of the difficulties of DNA extraction from sporocysts and availability of
      distinguishing genetic markers. Some of these species can be distinguished by
      bioassay; S. neurona and S. speeri are infective to gamma interferon gene
      knockout (KO) mice, but not to budgerigars (Melopsittacus undulatus); whereas S.
      falcatula and S. lindsayi are infective to budgerigars but not to KO mice. The
      natural intermediate host of S. speeri is unknown. In the present study,
      development of sarcocysts of S. speeri in the KO mice is described. Sarcocysts
      were first seen at 12 days post-inoculation (p.i.), and they became macroscopic
      (up to 4 mm long) by 25 days p.i. The structure of the sarcocyst wall did not
      change from the time bradyzoites had formed at 50-220 days p.i. Sarcocysts
      contained unique villar protrusions, 'type 38'. The polymerase chain reaction
      amplifications and sequences analysis of three nuclear loci (18S rRNA, 28S rRNA
      and ITS1) and two mitochondrial loci (cox1 and cytb) of S. speeri isolate from an
      Argentinean opossum (D. albiventris) confirmed its membership among species of
      Sarcocystis and indicated an especially close relationship to another parasite in
      this genus that employs opossums as its definitive host, S. neurona. These
      results should be useful in finding natural intermediate host of S. speeri. 

PMID- 26303094
TI  - CD229 Expression on Bone Marrow Plasma Cells from Patients with Multiple Myeloma
      and Monoclonal Gammopathies of Uncertain Significance.

PMID- 26303095
TI  - Algicidal microorganisms and secreted algicides: New tools to induce microalgal
      cell disruption.
AB  - Cell disruption is one of the most critical steps affecting the economy and
      yields of biotechnological processes for producing biofuels from microalgae.
      Enzymatic cell disruption has shown competitive results compared to mechanical or
      chemical methods. However, the addition of enzymes implies an associated cost in
      the overall production process. Recent studies have employed algicidal
      microorganisms to perform enzymatic cell disruption and degradation of microalgae
      biomass in order to reduce this associated cost. Algicidal microorganisms induce
      microalgae growth inhibition, death and subsequent lysis. Secreted algicidal
      molecules and enzymes produced by bacteria, cyanobacteria, viruses and the
      microalga themselves that are capable of inducing algal death are classified, and
      the known modes of action are described along with insights into cell-to-cell
      interaction and communication. This review aims to provide information regarding
      microalgae degradation by microorganisms and secreted algicidal substances that
      would be useful for microalgae cell breakdown in biofuels production processes. A
      better understanding of algae-to-algae communication and the specific mechanisms
      of algal cell lysis is expected to be an important breakthrough for the broader
      application of algicidal microorganisms in biological cell disruption and the
      production of biofuels from microalgae biomass. 

PMID- 26303096
TI  - White biotechnology: State of the art strategies for the development of
      biocatalysts for biorefining.
AB  - White biotechnology is a term that is now often used to describe the
      implementation of biotechnology in the industrial sphere. Biocatalysts (enzymes
      and microorganisms) are the key tools of white biotechnology, which is considered
      to be one of the key technological drivers for the growing bioeconomy.
      Biocatalysts are already present in sectors such as the chemical and agro-food
      industries, and are used to manufacture products as diverse as antibiotics, paper
      pulp, bread or advanced polymers. This review proposes an original and global
      overview of highly complementary fields of biotechnology at both enzyme and
      microorganism level. A certain number of state of the art approaches that are now
      being used to improve the industrial fitness of biocatalysts particularly focused
      on the biorefinery sector are presented. The first part deals with the
      technologies that underpin the development of industrial biocatalysts, notably
      the discovery of new enzymes and enzyme improvement using directed evolution
      techniques. The second part describes the toolbox available by the cell engineer
      to shape the metabolism of microorganisms. And finally the last part focuses on
      the 'omic' technologies that are vital for understanding and guide microbial
      engineering toward more efficient microbial biocatalysts. Altogether, these
      techniques and strategies will undoubtedly help to achieve the challenging task
      of developing consolidated bioprocessing (i.e. CBP) readily available for
      industrial purpose. 

PMID- 26303097
TI  - Outcome predictors in cardiopulmonary resuscitation facilitated by extracorporeal
      membrane oxygenation.
AB  - INTRODUCTION: Cardiac arrest is the major cause of sudden death in developed
      countries. Extracorporeal cardiopulmonary resuscitation (ECPR) employs
      extracorporeal membrane oxygenation (ECMO) in patients without return of
      spontaneous circulation (ROSC) by conventional cardiopulmonary resuscitation
      (CPR). Aim of the current study was to assess short- and long-term outcome in
      patients treated with ECPR in our tertiary center and to identify predictors of
      outcome. METHODS: We retrospectively collected data of all patients treated with
      ECPR at our institution from 2002 to 2013. Outcome was assessed according to
      patient records; good neurological outcome was defined as cerebral performance
      category 1 or 2. Quality of life data was collected using EQ-5 questionnaire. Uni
      and multivariate analysis was applied to identify predictors of outcome.
      RESULTS: One-hundred and seventeen patients were included into the study. Weaning
      from ECMO was successful in 61 (52 %) patients. Thirty-day survival endpoint was
      achieved by 27 (23 %) patients. Good neurological outcome was present in 17 (15
      %) patients. Multivariate analysis revealed baseline serum lactate as the
      strongest predictor of outcome, whereas age and out-of-hospital CPR did not
      predict outcome. The optimal lactate cut-off to discriminate outcome was
      determined at 4.6 mmol/l [HR 3.55 (2.29-5.49), p < 0.001, log-rank test].
      CONCLUSION: ECPR represents a treatment option in patients without ROSC after
      conventional CPR rescuing 15 % of patients with good neurological outcome. Serum
      lactate may play a crucial role in patient selection for ECPR.

PMID- 26303098
TI  - [Cystic mediastinal schwannoma appended to the vagus nerve].
AB  - INTRODUCTION: Schwannomas are a form of rare tumor, arising from neural tissue
      and representing 2 % of mediastinal tumors. They are usually located in the
      posterior mediastinum, most often in the paravertebral gutters and typically
      appended to intercostal nerves. CASE REPORTS: We report two cases of unusual
      mediastinal schwannomas, appended to the vagus nerve. The schwannoma was located
      in the subcarinal region in the first case and in the right para-tracheal region
      in the second case. The lesions were thought to be bronchogenic cysts
      preoperatively in both cases because of a cystic appearance on preoperative CT
      scan and endobronchial ultrasonography. A surgical approach was adopted to remove
      the tumors. Video-assisted thoracoscopy was used in one case and robotic-assisted
      surgery in the second case, without any complication, allowing for complete
      resection and to establish a certain pathological diagnosis. CONCLUSION: Despite
      this location and cystic presentation being unusual, schwannoma should be
      considered as a possible cause of cystic lesions in the mediastinum. Minimally
      invasive surgery allows for complete resection and definitive pathological
      diagnosis.

PMID- 26303100
TI  - Macrophage activation in human diseases.
AB  - It is becoming increasingly accepted that macrophages play a crucial role in many
      diseases associated with chronic inflammation, including atherosclerosis,
      obesity, diabetes, cancer, skin diseases, and even neurodegenerative diseases. It
      is therefore not surprising that macrophages in human diseases have gained
      significant interest during the last years. Molecular analysis combined with more
      sophisticated murine disease models and the application of genome-wide
      technologies has resulted in a much better understanding of the role of
      macrophages in human disease. We highlight important gain of knowledge during the
      last years for tumor-associated macrophages, and for macrophages in
      atherosclerosis, obesity and wound healing. Albeit these exciting findings
      certainly pave the way to novel diagnostics and therapeutics, several hurdles
      still need to be overcome. We propose a general outline for future research and
      development in disease-related macrophage biology based on integrating (1) genome
      wide technologies, (2) direct human sampling, and (3) a dedicated use of in vivo
      model systems.

PMID- 26303099
TI  - Mass Spectrometry-based PhyloProteomics (MSPP): A novel microbial typing Method.
AB  - MALDI-TOF-MS of microorganisms, which identifies microbes based on masses of high
      abundant low molecular weight proteins, is rapidly advancing to become another
      standard method in clinical routine laboratory diagnostics. Allelic isoforms of
      these proteins result in varying masses of detectable biomarker ions. These
      variations give rise to a novel typing method for microorganisms named mass
      spectrometry-based phyloproteomics (MSPP). The base of MSPP is an amino acid
      sequence list of allelic isoforms caused by non-synonymous mutations in biomarker
      genes, which were detectable as mass shifts in an overlay of calibrated MALDI-TOF
      spectra. Thus, for each isolate a combination of amino acid sequences can be
      deduced from the scheme of recordable biomarker masses. Performing comparably to
      laborious multilocus and whole genome sequence typing (wgMLST)-approaches it is
      feasible to build phyloproteomic dendrograms using hierarchical cluster analysis.
      MSPP bears a high potential especially for identification of chromosomal
      localised virulence or antimicrobial resistance factors associated with
      evolutionary relatedness. In this study the principle of MSPP-typing was
      demonstrated on a Campylobacter jejuni ssp. jejuni isolate collection and MSPP
      was compared to MLST. 

PMID- 26303101
TI  - Tear Cytokines as Biomarkers for Chronic Graft-versus-Host Disease.
AB  - We investigated the tear cytokine profiles in patients who underwent stem cell
      transplantation (SCT) and attempted to evaluate whether tear cytokines are
      associated with the presence of systemic chronic graft-versus-host disease
      (GVHD), regardless of ocular GVHD status. We also tested tear cytokines as
      biomarkers for chronic ocular GVHD severity. Forty-four patients who underwent
      SCT were enrolled and their diagnosis of chronic GVHD was confirmed. Ocular
      surface parameters and tear cytokine profiles were evaluated and the correlations
      between concentrations of cytokines and ocular surface parameters or several
      chronic ocular GVHD severity scales were evaluated. Tear interleukin (IL)-2, IL
      10, IL-17alpha, interferon (IFN)-gamma, IL-6, and tumor necrosis factor (TNF)
      alpha were elevated in patients with chronic systemic GVHD compared with patients
      without chronic systemic GVHD. Receiver-operating characteristic curve analysis
      revealed that area under the curve (AUC) values for tear IL-10 (AUC = .795), IL
      17alpha (AUC = .821), IL-6 (AUC = .912), and TNF-alpha (AUC = .910) were
      significantly correlated with the presence of chronic GVHD (all P < .001). Tear
      IL-10, IL-6, and TNF-alpha showed a stronger correlation with ocular surface
      parameters than other cytokines and these cytokines also correlated with several
      chronic ocular GVHD severity scales (all P < .05). Our data suggest the tear
      cytokines are useful biomarkers for the diagnosis of chronic GVHD after SCT and
      chronic ocular GVHD severity.

PMID- 26303103
TI  - Hematopoietic Cell Transplantation in Patients with Medication-Related
      Osteonecrosis of the Jaws.
AB  - Patients with medication-related osteonecrosis of the jaw (MRONJ) are at risk for
      developing infections and often require long-term antimicrobial therapy for
      management. It is unclear whether patients with multiple myeloma (MM) who develop
      MRONJ experience increased morbidity when they undergo hematopoietic cell
      transplantation (HCT). The aim of this study was to characterize the course of
      HCT in MM patients with MRONJ. A retrospective chart review was conducted for
      patients with MM and MRONJ who underwent HCT between December 2005 and December
      2014. Data collected included bisphosphonate use, MRONJ stage, positive blood
      cultures, number of febrile days, and length of hospital stay. Eleven patients
      (median age, 61; range, 46 to 71) fulfilled the criteria. Patients received
      zoledronic acid (72.7%), pamidronate (18.1%), or a combination of both (9%). At
      the time of HCT, 10 patients were in stage 1 MRONJ with 1 in stage 0. All
      patients had only mandibular involvement. No patient developed pain/infection at
      the MRONJ site during hospitalization. Bacteremia with positive blood cultures
      for Staphylococcus aureus occurred in 3 patients (27.2%), and 4 patients (36.3%)
      developed fever lasting between 4 to 6 days (of who 1 had positive blood
      cultures). The median length of hospital stay was 17 days (range, 7 to 22 days).
      These data suggests that patients with MM and MRONJ who undergo HCT are not at
      increased risk of developing symptoms associated with the MRONJ site or HCT
      related infectious complications, and their MRONJ is not worsened by HCT. 

PMID- 26303102
TI  - Long-Term Safety Outcomes in Patients with Hematological Malignancies Undergoing
      Autologous Hematopoietic Stem Cell Transplantation Treated with Palifermin to
      Prevent Oral Mucositis.
AB  - The purpose of our study was to compare long-term safety outcomes (overall
      survival, disease progression, and incidence of secondary malignancies) between
      palifermin and placebo in the prevention of oral mucositis in patients with
      hematological malignancies undergoing autologous hematopoietic stem cell
      transplantation (HSCT). Patients were enrolled between 1997 and 2005 into 4 phase
      I to III studies (3 double-blind placebo-controlled and 1 open-label) conducted
      at 31 sites in Australia, Europe, and the United States. Survival outcomes
      (overall survival, progression-free survival) were compared using hazard ratios
      (HRs) estimated with a Cox model that included treatment group, baseline age,
      disease type, Eastern Cooperative Oncology Group performance status, country, and
      presence of prior radiotherapy as covariates. The incidence of secondary
      malignancies was compared with a chi-square test. A total of 672 patients were
      randomized into the studies (428 palifermin and 244 placebo). The median follow
      up time for subjects alive at last visit was 7.9 years (range, .1 to 14.9) for
      palifermin and 8.8 years (range, .1 to 14.8) for placebo. Palifermin-treated
      patients had overall survival (HR, 1.01; 95% confidence interval [CI], .78 to
      1.31; P = .921) and progression-free survival times (HR, 1.04; 95% CI, .83 to
      1.31; P = .733) that were comparable with placebo-treated patients. Secondary
      malignancies were reported by 13% of palifermin-treated patients versus 11% of
      placebo patients (P = .477). Breakdown into secondary hematological malignancies
      (7% versus 6%) or solid tumors (6% versus 6%) did not suggest any differences
      between the treatment groups. After a follow-up of up to 15 years, comparable
      long-term safety outcomes (overall survival, progression-free survival, and
      incidence of secondary malignancies) were observed for palifermin- and placebo
      treated patients undergoing autologous HSCT.

PMID- 26303104
TI  - Benchmarking human epithelial type 2 interphase cells classification methods on a
      very large dataset.
AB  - OBJECTIVE: This paper presents benchmarking results of human epithelial type 2
      (HEp-2) interphase cell image classification methods on a very large dataset. The
      indirect immunofluorescence method applied on HEp-2 cells has been the gold
      standard to identify connective tissue diseases such as systemic lupus
      erythematosus and Sjogren's syndrome. However, the method suffers from numerous
      issues such as being subjective, time consuming and labor intensive. This has
      been the main motivation for the development of various computer-aided diagnosis
      systems whose main task is to automatically classify a given cell image into one
      of the predefined classes. METHODS AND MATERIAL: The benchmarking was performed
      in the form of an international competition held in conjunction with the
      International Conference of Image Processing in 2013: fourteen teams, composed of
      practitioners and researchers in this area, took part in the initiative. The
      system developed by each team was trained and tested on a very large HEp-2 cell
      dataset comprising over 68,000 images of HEp-2 cell. The dataset contains cells
      with six different staining patterns and two levels of fluorescence intensity.
      For each method we provide a brief description highlighting the design choices
      and an in-depth analysis on the benchmarking results. RESULTS: The staining
      pattern recognition accuracy attained by the methods varies between 47.91% and
      slightly above 83.65%. However, the difference between the top performing method
      and the seventh ranked method is only 5%. In the paper, we also study the
      performance achieved by fusing the best methods, finding that a recognition rate
      of 85.60% is reached when the top seven methods are employed. CONCLUSIONS: We
      found that highest performance is obtained when using a strong classifier
      (typically a kernelised support vector machine) in conjunction with features
      extracted from local statistics. Furthermore, the misclassification profiles of
      the different methods highlight that some staining patterns are intrinsically
      more difficult to recognize. We also noted that performance is strongly affected
      by the fluorescence intensity level. Thus, low accuracy is to be expected when
      analyzing low contrasted images.

PMID- 26303105
TI  - A fuzzy-ontology-oriented case-based reasoning framework for semantic diabetes
      diagnosis.
AB  - OBJECTIVE: Case-based reasoning (CBR) is a problem-solving paradigm that uses
      past knowledge to interpret or solve new problems. It is suitable for experience
      based and theory-less problems. Building a semantically intelligent CBR that
      mimic the expert thinking can solve many problems especially medical ones.
      METHODS: Knowledge-intensive CBR using formal ontologies is an evolvement of this
      paradigm. Ontologies can be used for case representation and storage, and it can
      be used as a background knowledge. Using standard medical ontologies, such as
      SNOMED CT, enhances the interoperability and integration with the health care
      systems. Moreover, utilizing vague or imprecise knowledge further improves the
      CBR semantic effectiveness. This paper proposes a fuzzy ontology-based CBR
      framework. It proposes a fuzzy case-base OWL2 ontology, and a fuzzy semantic
      retrieval algorithm that handles many feature types. MATERIAL: This framework is
      implemented and tested on the diabetes diagnosis problem. The fuzzy ontology is
      populated with 60 real diabetic cases. The effectiveness of the proposed approach
      is illustrated with a set of experiments and case studies. RESULTS: The resulting
      system can answer complex medical queries related to semantic understanding of
      medical concepts and handling of vague terms. The resulting fuzzy case-base
      ontology has 63 concepts, 54 (fuzzy) object properties, 138 (fuzzy) datatype
      properties, 105 fuzzy datatypes, and 2640 instances. The system achieves an
      accuracy of 97.67%. We compare our framework with existing CBR systems and a set
      of five machine-learning classifiers; our system outperforms all of these
      systems. CONCLUSION: Building an integrated CBR system can improve its
      performance. Representing CBR knowledge using the fuzzy ontology and building a
      case retrieval algorithm that treats different features differently improves the
      accuracy of the resulting systems.

PMID- 26303106
TI  - Robust feature selection to predict tumor treatment outcome.
AB  - OBJECTIVE: Recurrence of cancer after treatment increases the risk of death. The
      ability to predict the treatment outcome can help to design the treatment
      planning and can thus be beneficial to the patient. We aim to select predictive
      features from clinical and PET (positron emission tomography) based features, in
      order to provide doctors with informative factors so as to anticipate the outcome
      of the patient treatment. METHODS: In order to overcome the small sample size
      problem of datasets usually met in the medical domain, we propose a novel wrapper
      feature selection algorithm, named HFS (hierarchical forward selection), which
      searches forward in a hierarchical feature subset space. Feature subsets are
      iteratively evaluated with the prediction performance using SVM (support vector
      machine). All feature subsets performing better than those at the preceding
      iteration are retained. Moreover, as SUV (standardized uptake value) based
      features have been recognized as significant predictive factors for a patient
      outcome, we propose to incorporate this prior knowledge into the selection
      procedure to improve its robustness and reduce its computational cost. RESULTS:
      Two real-world datasets from cancer patients are included in the evaluation. We
      extract dozens of clinical and PET-based features to characterize the patient's
      state, including SUV parameters and texture features. We use leave-one-out cross
      validation to evaluate the prediction performance, in terms of prediction
      accuracy and robustness. Using SVM as the classifier, our HFS method produces
      accuracy values of 100% and 94% on the two datasets, respectively, and robustness
      values of 89% and 96%. Without accuracy loss, the prior-based version (pHFS)
      improves the robustness up to 100% and 98% on the two datasets, respectively.
      CONCLUSIONS: Compared with other feature selection methods, the proposed HFS and
      pHFS provide the most promising results. For our HFS method, we have empirically
      shown that the addition of prior knowledge improves the robustness and
      accelerates the convergence.

PMID- 26303107
TI  - Countering Cognitive Bias: Tips for Recognizing the Impact of Potential Bias on
      Research.

PMID- 26303109
TI  - Correlation of Physical Activities and Breast Cancer Characteristics: A
      Prospective Analysis with Special Focus on Triple Negative Breast Cancer.
AB  - OBJECTIVE: Several studies have demonstrated that daily physical activity (PA)
      prevents the development of breast cancer. Our objective was to examine the
      relationship between PA and clinical and biological tumor characteristics in
      breast cancer patients in order to determine the impact of energy expenditure
      (EE) on tumor prognosis. METHODS: We pooled data from two prospective studies,
      including a total of 121 breast cancer patients. The measure of PA was done using
      the self-completion Population Physical Activity Questionnaire, which was
      answered by each patient. RESULTS: Ten patients harbored triple negative (TN)
      tumors. The mean body mass index (BMI) in the general population and in patients
      with TN tumors was 24.3 and 25.6, respectively. The mean daily EE (DEE) was
      10,266 kJ*24 h(-1) in the general population and 11,212 kJ*24 h(-1) in patients
      with TN tumors. In the whole population, there was an inverse statistical
      correlation between BMI and DEE, rest, low PA, and high PA (p=0.0002, p=0.003,
      p<0001, and p=0.03, respectively). There was a positive correlation between
      negative estrogen receptor status and intensive PA (p=0.041) and DEE (p=0.007).
      For TN tumors, there was no significant correlation between BMI and categories of
      EE. CONCLUSIONS: Lifestyle (weight regulation, PA) should be adapted and
      personalized according to biological, clinical, and epidemiological
      characteristics of the tumors.

PMID- 26303108
TI  - Sialic acid catabolism drives intestinal inflammation and microbial dysbiosis in
      mice.
AB  - Rapid shifts in microbial composition frequently occur during intestinal
      inflammation, but the mechanisms underlying such changes remain elusive. Here we
      demonstrate that an increased caecal sialidase activity is critical in conferring
      a growth advantage for some bacteria including Escherichia coli (E. coli) during
      intestinal inflammation in mice. This sialidase activity originates among others
      from Bacteroides vulgatus, whose intestinal levels expand after dextran sulphate
      sodium administration. Increased sialidase activity mediates the release of
      sialic acid from intestinal tissue, which promotes the outgrowth of E. coli
      during inflammation. The outburst of E. coli likely exacerbates the inflammatory
      response by stimulating the production of pro-inflammatory cytokines by
      intestinal dendritic cells. Oral administration of a sialidase inhibitor and low
      levels of intestinal alpha2,3-linked sialic acid decrease E. coli outgrowth and
      the severity of colitis in mice. Regulation of sialic acid catabolism opens new
      perspectives for the treatment of intestinal inflammation as manifested by E.
      coli dysbiosis. 

PMID- 26303110
TI  - Influence of valproic acid concentration and polymorphism of UGT1A4*3, UGT2B7 
      161C > T and UGT2B7*2 on serum concentration of lamotrigine in Chinese epileptic
      children.
AB  - PURPOSE: To investigate the impact of valproic acid (VPA) and genetic
      polymorphism of the major metabolizing enzyme (UGT1A4, UGT2B7) of lamotrigine
      (LTG) and VPA on LTG concentration in Chinese epileptic children. METHODS: Three
      single nucleotide polymorphisms (UGT1A4*3, UGT2B7 -161C > T and UGT2B7*2) were
      analyzed by polymerase chain reaction-restriction fragment length polymorphism or
      direct DNA sequencing. The concentrations of LTG and VPA were measured by high
      performance liquid chromatography (HPLC) and fluorescence polarization
      immunoassay, respectively. The adjusted concentration of LTG was defined as the
      concentration-to-dose-ratio (CDRLTG). Data analysis was performed using IBM SPSS
      Statistics 21.0. RESULTS: A total of 56 patients treated with LTG as monotherapy
      and 158 patients treated with LTG plus VPA were included in this study. In the
      polytherapy group, LTG concentration showed a good linear relationship with
      gender, age, daily LTG dose, VPA concentration, and UGT1A4*3 polymorphism, but
      had no relationship with the polymorphism of UGT2B7 -161C > T or UGT2B7*2.
      Moreover, LTG concentration and CDRLTG for the UGT1A4*3 were higher compared to
      UGT1A4*1 (LTG: 7.24 +/- 3.51 vs 5.26 +/- 3.27 MUg/mL, p = 0.001; CDRLTG: 2.75 +/-
      1.02 vs 2.14 +/- 0.96 MUg/mL per mg/kg, p < 0.001, respectively). In the
      monotherapy group, there was no statistical difference between UGT1A4*3 and
      UGT1A4*1 in LTG concentration or CDRLTG. The patients in the polytherapy group
      were divided into two subgroups according to VPA concentration (lower/higher: 10
      50/50-125 MUg/mL). CDRLTG values of the patients carrying the UGT1A4*3 genotype
      were higher compared to UGT1A4*1*1 (2.86 +/- 1.03 vs 2.22 +/- 0.94 MUg/mL per
      mg/kg, p = 0.001) only when the VPA concentration was higher. CONCLUSIONS:
      UGT1A4*3 polymorphism had an effect on LTG concentration only with VPA co
      administration, and the effect was remarkable when VPA concentration was higher.

PMID- 26303111
TI  - Effective CSF concentrations achieved with continuous-infusion flucloxacillin in
      a child.

PMID- 26303112
TI  - Psychometrics and its discontents: an historical perspective on the discourse of
      the measurement tradition.
AB  - Psychometrics has recently undergone extensive criticism within the medical
      education literature. The use of quantitative measurement using psychometric
      instruments such as response scales is thought to emphasize a narrow range of
      relevant learner skills and competencies. Recent reviews and commentaries suggest
      that a paradigm shift might be presently underway. We argue for caution, in that
      the psychometrics approach and the quantitative account of competencies that it
      reflects is based on a rich discussion regarding measurement and scaling that led
      to the establishment of this paradigm. Rather than reflecting a homogeneous
      discipline focused on core competencies devoid of consideration of context, the
      psychometric community has a history of discourse and debate within the field,
      with an acknowledgement that the techniques and instruments developed within
      psychometrics are heuristics that must be used pragmatically. 

PMID- 26303113
TI  - Gender, religion, and sociopolitical issues in cross-cultural online education.
AB  - Cross-cultural education is thought to develop critical consciousness of how
      unequal distributions of power and privilege affect people's health. Learners in
      different sociopolitical settings can join together in developing critical
      consciousness-awareness of power and privilege dynamics in society-by means of
      communication technology. The aim of this research was to define strengths and
      limitations of existing cross-cultural discussions in generating critical
      consciousness. The setting was the FAIMER international fellowship program for
      mid-career interdisciplinary health faculty, whose goal is to foster global
      advancement of health professions education. Fellows take part in participant
      led, online, written, task-focused discussions on topics like professionalism,
      community health, and leadership. We reflexively identified text that brought
      sociopolitical topics into the online environment during the years 2011 and 2012
      and used a discourse analysis toolset to make our content analysis relevant to
      critical consciousness. While references to participants' cultures and
      backgrounds were infrequent, narratives of political-, gender-, religion-, and
      other culture-related topics did emerge. When participants gave accounts of their
      experiences and exchanged cross-cultural stories, they were more likely to
      develop ad hoc networks to support one another in facing those issues than
      explore issues relating to the development of critical consciousness. We suggest
      that cross-cultural discussions need to be facilitated actively to transform
      learners' frames of reference, create critical consciousness, and develop
      cultural competence. Further research is needed into how to provide a safe
      environment for such learning and provide faculty development for the skills
      needed to facilitate these exchanges.

PMID- 26303114
TI  - A 1D anionic coordination polymer showing superior Congo Red sorption and its dye
      composite exhibiting remarkably enhanced photocurrent response.
AB  - Instant adsorption of Congo Red (CR) by a 1D coordination polymer,
      [(H2L)0.5][Zn(1,2,3-BTA)(H2O)].2H2O (1.2H2O), leads to the formation of a unique
      dye composite 1.0.75CR.6H2O, which demonstrates a remarkably enhanced
      photocurrent response compared to that of its precursor.

PMID- 26303115
TI  - Case report of a young stroke patient showing interim normalization of the MRI
      diffusion-weighted imaging lesion.
AB  - BACKGROUND: In acute ischemic stroke, diffusion weighted imaging (DWI) shows
      hyperintensities and is considered to indicate irreversibly damaged tissue. We
      present the case of a young stroke patient with unusual variability in the
      development of signal intensities within the same vessel territory. CASE
      PRESENTATION: A 35-year-old patient presented with symptoms of global aphasia and
      hypesthesia of the left hand. MRI demonstrated a scattered lesion in the MCA
      territory. After rtPA therapy the patient received further MRI examination, three
      times on day 1, and once on day 2, 3, 5 and 43. The posterior part of the lesion
      showed the usual pattern with increasing DWI hyperintensity and decreased ADC, as
      well as delayed FLAIR positivity. However, the anterior part of the lesion, which
      was clearly visible in the first examination completely normalized on the first
      day and only reappeared on day 2. This was accompanied by a normalization of the
      ADC as well as an even further delayed FLAIR positivity. CONCLUSION: We showed
      that interim normalization of DWI and ADC in the acute phase can not only be
      found in rodent models of stroke, but also in humans. We propose that DWI lesion
      development might be more variable during the first 24 h after stroke than
      previously assumed.

PMID- 26303116
TI  - Factors implicated in the initiation of human parturition in term and preterm
      labor: a review.
AB  - After accommodating the pregnancy for an average of 40 weeks, the uterus expels
      the fetus, the placenta and the membranes through the birth canal in a process
      named parturition. The absolute sequence of events that trigger and sustain human
      parturition are not yet fully clarified. Evidence suggests that spontaneous
      preterm and term labor seem to share a common inflammatory pathway. However,
      there are several other factors being involved in the initiation of human
      parturition. Placental corticotropin releasing hormone production seems to serve
      as a placental clock that might be set to ring earlier or later determining the
      duration of pregnancy and timing of labor. Estrogens do not cause contractions
      but their properties seem to capacitate uterus to coordinate and enhance
      contractions. Cytokines, prostaglandins, nitric oxide and steroids seem also to
      induce ripening by mediating remodeling of the extracellular matrix and collagen.
      Infection and microbe invasion resulting in chorioamnionitis also represents a
      common cause of early preterm labour. This review provides an overview of all
      these factors considered to be implicated in the initiation of human parturition.

PMID- 26303117
TI  - Ultra-stretchable and skin-mountable strain sensors using carbon nanotubes
      Ecoflex nanocomposites.
AB  - Super-stretchable, skin-mountable, and ultra-soft strain sensors are presented by
      using carbon nanotube percolation network-silicone rubber nanocomposite thin
      films. The applicability of the strain sensors as epidermal electronic systems,
      in which mechanical compliance like human skin and high stretchability (epsilon >
      100%) are required, has been explored. The sensitivity of the strain sensors can
      be tuned by the number density of the carbon nanotube percolation network. The
      strain sensors show excellent hysteresis performance at different strain levels
      and rates with high linearity and small drift. We found that the carbon nanotube
      silicone rubber based strain sensors possess super-stretchability and high
      reliability for strains as large as 500%. The nanocomposite thin films exhibit
      high robustness and excellent resistance-strain dependency for over ~1380%
      mechanical strain. Finally, we performed skin motion detection by mounting the
      strain sensors on different parts of the body. The maximum induced strain by the
      bending of the finger, wrist, and elbow was measured to be ~ 42%, 45% and 63%,
      respectively.

PMID- 26303118
TI  - Fish oil administration mediates apoptosis of Walker 256 tumor cells by
      modulation of p53, Bcl-2, caspase-7 and caspase-3 protein expression.
AB  - BACKGROUND: Several studies have been shown pro-apoptotic effects of fish oil
      (FO), rich in n-3 polyunsaturated fatty acids (n-3 PUFA) on cancer cells.
      Nevertheless, few in vivo experiments have provided data of its ability on
      apoptosis protein expression in tumor tissue. Thus, in this study we investigate
      the effect of FO supplementation on apoptosis protein expression in Walker 256
      tumor bearing rats. Male Wistar rats were randomly assigned to three groups: fed
      with regular chow (W); fed regular chow supplemented with FO (WFO) or coconut fat
      (WCO) (1 g/kg body weight/daily). After thirty days, all animals were inoculated
      subcutaneously with Walker 256 tumor cells. FINDINGS: Protein expression was done
      by western blotting in Walker 256 tumor tissue samples. FO decreased the Bcl
      2/Bax ratio (p < 0.05) and increased the p53 (p < 0.05), cleaved caspase-7 (p <
      0.05) and cleaved caspase-3 (p < 0.05) in Walker 256 tumor tissue. CONCLUSIONS:
      Our data suggest that the pro-apoptotic effect of FO in Walker 256 tumor is
      related with specifics cleaved caspases.

PMID- 26303119
TI  - Active inflammatory biomarkers in oral lichen planus.
AB  - Oral lichen planus (OLP) is a chronic disease, with a central role to cell
      mediated autoimmunity. Osteopontin promotes migration and recruitment of immune
      cells, CD44 is its receptor, and Survivin seems to be important in skin/mucosa
      homeostasis. The aim of this study was to investigate their expression in biopsy
      specimens of patients with different OLP clinical types and healthy
      controls.Biopsy specimens from 30 patients with OLP (15 atrophic and 15
      hyperplastic) and 15 healthy controls were subjected to immune-histochemical
      analysis, to detect the expression of osteopontin, CD44, and Survivin in oral
      epithelia. The distributions of positively stained cells were evaluated with a
      quantitative method, while the inflammation degree was evaluated with a semi
      quantitative one.Expression of osteopontin and CD44 was higher in OLP than
      controls, while Survivin expression was lower in OLP patients. There was a
      greater reduction of Survivin expression in atrophic OLP than hyperplastic OLP. A
      correlation between osteopontin expression and a high degree of inflammation was
      found. Furthermore, Survivin expression was higher in cases with low intensity of
      inflammation.Osteopontin, CD44, and Survivin seem to be involved in OLP
      pathogenesis, and further investigations are needed for clarifying their role in
      this oral disease. 

PMID- 26303120
TI  - Immunomodulatory and antimicrobial efficacy of Lactobacilli against
      enteropathogenic infection of Salmonella typhi: In-vitro and in-vivo study.
AB  - Salmonellosis-induced diarrhea, is one of the commonest cause of childhood
      mortality in developing countries. Using of probiotics is viewed as a promising
      means for reducing the pathogenic loads of bacterial infection. The current study
      aimed to evaluate the potential antimicrobial and immunomodulatory efficacy of
      isolated lactobacillus strains against the enteropathogenic effect of S. Typhi.
      Different Lactobacillus strains were isolated from 13 dairy products. Their
      antimicrobial activities were tested against different bacterial strains. Six
      groups of CD1 mice were treated for 8 days as follows: group (1) untreated
      control; group (2) was challenged with single inoculation S. typhi, and groups
      (3) and (4) were treated with Lactobacillus plantarum (LA5) or Lactobacillus
      paracsi (LA7) for 7 days, respectively. Groups (5) and (6) were challenged with
      S. typhi, and then treated with either LA5 or LA 7 for 7 days, respectively.
      Isolated Lactobacillus showed antimicrobial activity against wide range of
      bacterial strains. Salmonellosis showed high widal titer, induced significant
      disturbance of TNF and IL-1beta, while sever changes of the histological patterns
      of the intestinal villi and hepatocytes have been illustrated. LA5 or LA7
      succeeded to eradicate typhoid infection, restore the values of inflammatory
      cytokines to typical levels of control group, and improve histological pictures
      of intestinal and hepatic tissues. It can be concluded that lactobacilli are
      promising candidate in protection and eradication against bacterial infection
      induced by S. Typhi due to its antimicrobial, anti-inflammatory, and
      immunomodulatory activities. 

PMID- 26303121
TI  - Foix-Chavany-Marie Syndrome after Unilateral Stroke.

PMID- 26303123
TI  - Alopecia, palmoplantar keratoderma, skin fragility and follicular hyperkeratoses
      due to compound heterozygous mutations in desmoplakin.
AB  - Inherited mutations in desmosome genes can present with a spectrum of skin, hair
      and cardiac abnormalities. Here we describe a 4-year-old Turkish boy with a
      cardio-cutaneous syndrome resulting from compound heterozygous nonsense mutations
      in desmoplakin. Early recognition of such cases by clinical awareness of the
      dermatological features and molecular diagnostics can improve patient management
      through early cardiac support, although the risk of cardiomyopathy and
      arrhythmias poses a major health concern.

PMID- 26303122
TI  - Expression of Semaphorin 4A and its potential role in rheumatoid arthritis.
AB  - INTRODUCTION: Semaphorin 4A (Sema4A) plays critical roles in many physiological
      and pathological processes including neuronal development, angiogenesis, immune
      response regulation, autoimmunity, and infectious diseases. The present study
      aimed to investigate its expression and biological activity in rheumatoid
      arthritis (RA). METHODS: RNA and protein were isolated from synovial tissues in
      RA and osteoarthritis (OA) patients. Treatment with recombinant human Sema4A
      (rhSema4A) or small interfering RNA (siRNA) was applied to examine its effect on
      the biological activity of synovial fibroblasts of RA (RASFs). Expression of
      Sema4A and NF-kappaB were measured by quantitative RT-PCR (qRT-PCR) and Western
      blot after lipopolysaccharide (LPS) stimulation. Chromatin immunoprecipitation
      (ChIP) and siRNA targeting p50 and p60 were applied to detect the regulation of
      Nuclear factor kappa (NF-kappaB) on Sema4A. Sema4A, interleukin 1beta (IL-1beta),
      interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) secretion were
      measured by ELISA-based assays. RESULTS: Increased levels of Sema4A were detected
      in the synovial tissue and fluid of patients with RA compared with those with OA.
      Furthermore, synovial fluid level of Sema4A correlated with Disease Activity
      Score (DAS) in RA. Treatment with rhSema4A promoted invasion of RASFs by
      upregulating the expression of Matrix metallopeptidase3 (MMP3), MMP9, alpha
      smooth muscle actin(alpha-SMA), and Vimentin, and exacerbated inflammation by
      promoting the production of IL-6 in RASFs, as well as IL-1beta and TNF-alpha in
      THP-1 cells. The induction of IL-6 and TNF-alpha by Sema4A was confirmed at the
      protein level in fluid samples from patients with RA. Knock-down experiments
      showed the participation of Plexin B1 towards rhSema4A in the induction of
      cytokines. In addition, LPS stimulation induced Sema4A expression in RASFs in an
      NF-kappaB-dependent manner, and rhSema4A treatment could also activate NF-kappaB
      signaling. CONCLUSIONS: These findings suggest an NF-kappaB-dependent modulation
      of Sema4A in the immune response. Further, increased expression of Sema4A is
      required to promote inflammation of RA.

PMID- 26303124
TI  - Further investigation of risk elements content in the bones of wild rodents from
      a polluted area in Slovakia.
AB  - BACKGROUND: Wild rodents are suitable for monitoring environmental pollution and
      exposure risk assessment for people living in contaminated areas. The content of
      selected risk elements in the femora of bank vole (Myodes glareolus), yellow
      necked mouse (Apodemus flavicollis) and wood mouse (Apodemus sylvaticus) was
      estimated from the Kolinany area of Slovakia, which is characterized by a high
      degree of environmental pollution. The rodents were trapped in February 2011
      using standard theriological methods. All animals (n = 32) were adult males in
      good physical condition. The concentrations of Fe, Cu, Zn and Ni in their bones
      were determined by atomic absorption spectrophotometry. RESULTS: The highest
      concentrations of Fe and Cu were detected in the bones of yellow-necked mouse.
      Significant differences were observed for the content of Fe between A.
      flavicollis and M. glareolus (P < 0.05). The highest levels of Zn and Ni were
      found in the femora of wood mouse; however, significant differences were not
      detected between the rodents. Moreover, the concentrations of Cu, Zn and Ni were
      significantly higher in the bones of all three species (P < 0.05) in comparison
      with the values obtained in the same animal species at the same site in February
      2007. CONCLUSIONS: Our results demonstrate an increased accumulation of Cu, Zn
      and Ni in the femora of M. glareolus, A. flavicollis and A. sylvaticus from the
      Kolinany area and thus indicate towards ongoing contamination of this locality.

PMID- 26303125
TI  - Exosomal MicroRNAs in Tissue Crosstalk.

PMID- 26303126
TI  - Computed Tomography of the Prostate Gland in Healthy Intact Dogs and Dogs with
      Benign Prostatic Hyperplasia.
AB  - To date, there is only scarce data on the evaluation of the prostate gland in
      dogs using computed tomography (CT). The aims of our study were to describe CT
      features of BPH in dogs and to determine the size of the prostate gland in
      healthy male dogs and dogs with benign prostatic hyperplasia (BPH) through CT.
      Additionally, we aimed to compare and establish the most useful parameters for CT
      measurements of the prostate in patients with BPH. The study population consisted
      of 20 healthy intact male dogs and 20 male intact dogs with confirmed BPH. Pre-
      and post-contrast CT studies were evaluated. The most common CT features in dogs
      with recognized BPH were symmetrical prostatomegaly and heterogeneity of the
      prostatic parenchyma. The mean prostatic density (D) was 56HU (+/-4.39) in pre
      contrast CT images and 84HU (+/-8) in post-contrast images in dogs with BPH. The
      mean prostatic length (L) was 43.87 mm (+/-11), the mean width (W) amounted to
      48.95 mm (+/-8.76) and the mean height (H) reached 44.9 mm (+/-9.48) in
      clinically affected patients. The mean ratios were: rL - 2,12 (+/-0.5); rW - 2.39
      (+/-0.53) and rH - 2.16 (+/-0.39) in the BPH group. The prostate should be
      considered to be enlarged when rL exceeds 3.05; rW exceeds 3.38 and rH exceeds
      2.94. Our findings indicated that CT is a useful tool in diagnosing prostate
      disorders, including BPH. The heterogeneity, density and ratios of prostatic
      length, width and height can be useful parameters in the diagnosis of BPH.

PMID- 26303127
TI  - Comparison of Toxicity Between Intensity-Modulated Radiotherapy and 3-Dimensional
      Conformal Radiotherapy for Locally Advanced Non-small-cell Lung Cancer.
AB  - BACKGROUND: The role of intensity-modulated radiotherapy (IMRT) in reducing
      treatment-related toxicity for locally advanced non-small-cell lung cancer
      (NSCLC) remains incompletely defined. We compared acute toxicity and oncologic
      outcomes in a large cohort of patients treated with IMRT or 3-dimensional
      conformal radiotherapy (3-DCRT), with or without elective nodal irradiation
      (ENI). METHODS: A single-institution retrospective review was performed
      evaluating 145 consecutive patients with histologically confirmed stage III NSCLC
      treated with definitive chemoradiotherapy. Sixty-five (44.8%) were treated with 3
      DCRT using ENI, 43 (30.0%) with 3-DCRT using involved-field radiotherapy (IFRT),
      and 37 (25.5%) with IMRT using IFRT. All patients received concurrent
      chemotherapy. Comparison of acute toxicities by treatment technique (IMRT vs. 3
      DCRT) and extent of nodal irradiation (3-DCRT-IFRT vs. 3-DCRT-ENI) was performed
      for grade 2 or higher esophagitis or pneumonitis, number of acute
      hospitalizations, incidence of opioid requirement, percutaneous endoscopic
      gastrostomy utilization, and percentage weight loss during treatment. Local
      control and overall survival were analyzed by the Kaplan-Meier method. RESULTS:
      We identified no significant differences in any measures of acute toxicity by
      treatment technique or extent of nodal irradiation. There was a trend toward
      lower rates of grade 2 or higher pneumonitis among IMRT patients compared to 3
      DCRT patients (5.4% vs. 23.0%; P = .065). Local control and overall survival were
      similar between cohorts. CONCLUSION: Acute and subacute toxicities were similar
      for patients treated with IMRT and with 3-DCRT with or without ENI, with a
      nonsignificant trend toward a reduction in pneumonitis with IMRT. Larger studies
      are needed to better define which patients will benefit from IMRT.

PMID- 26303128
TI  - A Clinical Prediction Tool Identifies Cases of Eosinophilic Esophagitis Without
      Endoscopic Biopsy: A Prospective Study.
AB  - OBJECTIVES: Eosinophilic esophagitis (EoE) is difficult to distinguish from
      gastroesophageal reflux (GERD) and other causes of dysphagia. We assessed the
      utility of a set of clinical and endoscopic features for predicting EoE without
      obtaining esophageal biopsies. METHODS: We prospectively enrolled consecutive
      adults undergoing outpatient upper endoscopy at the University of North Carolina
      from July 2011 through December 2013. Incident cases of EoE were diagnosed per
      consensus guidelines. Non-EoE controls had either GERD- or dysphagia-predominant
      symptoms. A predictive model containing clinical and endoscopic, but no
      histological, data was assessed. Receiver operator characteristic curves were
      constructed and the area under the curve (AUC) was calculated. RESULTS: A total
      of 81 EoE cases (mean age 38 years; 60% male; 93% white; 141 eosinophils per high
      power field (eos/hpf)) and 144 controls (mean age 52, 38% male; 82% white; 3
      eos/hpf) were enrolled. A combination of clinical (age, sex, dysphagia, food
      allergy) and endoscopic (rings, furrows, plaques, hiatal hernia) features was
      highly predictive of EoE. The AUC was 0.944, with sensitivity, specificity, and
      accuracy of 84, 97, and 92%. Similar values were seen after limiting controls to
      those with only reflux or dysphagia or to those with esophageal eosinophilia not
      due to EoE. CONCLUSIONS: We validated a set of clinical and endoscopic features
      to predict EoE with a high degree of accuracy and allow identification of those
      at very low risk of disease. Use of these predictors at the point-of-care will
      avoid the effort and expense of low-yield histological examinations for EoE.

PMID- 26303129
TI  - Altered Colonic Bacterial Fermentation as a Potential Pathophysiological Factor
      in Irritable Bowel Syndrome.
AB  - OBJECTIVES: Dysbiosis leading to abnormal intestinal fermentation has been
      suggested as a possible etiological mechanism in irritable bowel syndrome (IBS).
      We aimed to investigate the location and magnitude of altered intestinal
      bacterial fermentation in IBS and its clinical subtypes. METHODS: IBS patients
      who satisfied the Rome III criteria (114) and 33 healthy controls (HC) were
      investigated. Intestinal fermentation was assessed using two surrogate measures:
      intestinal intraluminal pH and fecal short-chain fatty acids (SCFAs).
      Intraluminal pH and intestinal transit times were measured in the small and large
      bowel using a wireless motility capsule (SmartPill) in 47 IBS and 10 HC. Fecal
      SCFAs including acetate, propionate, butyrate, and lactate were analyzed by
      capillary gas chromatography in all enrolled subjects. Correlations between
      intestinal pH, fecal SCFAs, intestinal transit time, and IBS symptom scores were
      analyzed. RESULTS: Colonic intraluminal pH levels were significantly lower in IBS
      patients compared with HC (total colonic pH, 6.8 for IBS vs. 7.3 for HC,
      P=0.042). There were no differences in total and segmental pH levels in the small
      bowel between IBS patients and HC (6.8 vs. 6.8, P=not significant). The
      intraluminal colonic pH differences were consistent in all IBS subtypes. Total
      SCFA level was significantly lower in C-IBS patients than in D-IBS and M-IBS
      patients and HC. The total SCFA level in all IBS subjects was similar with that
      of HC. Colonic pH levels correlated positively with colon transit time (CTT) and
      IBS symptoms severity. Total fecal SCFAs levels correlated negatively with CTT
      and positively with stool frequency. CONCLUSIONS: Colonic intraluminal pH is
      decreased, suggesting higher colonic fermentation, in IBS patients compared with
      HC. Fecal SCFAs are not a sensitive marker to estimate intraluminal bacterial
      fermentation.

PMID- 26303130
TI  - Cost-Effective Evaluation of Nonalcoholic Fatty Liver Disease With NAFLD Fibrosis
      Score and Vibration Controlled Transient Elastography.
AB  - OBJECTIVES: The risk of advanced fibrosis in nonalcoholic fatty liver disease
      (NAFLD) is traditionally assessed with a liver biopsy, which is both costly and
      associated with adverse events. METHODS: We sought to compare the cost
      effectiveness of four different strategies to assess fibrosis risk in patients
      with NAFLD: vibration controlled transient elastography (VCTE), the NAFLD
      fibrosis score (NFS), combination testing with NFS and VCTE, and liver biopsy
      (usual care). We developed a probabilistic decision analytical microsimulation
      state-transition model wherein we simulated a cohort of 10,000 50-year-old
      Americans with NAFLD undergoing evaluation by a gastroenterologist. VCTE
      performance was obtained from a prospective cohort of 144 patients with NAFLD.
      RESULTS: Both the NFS alone and the NFS/VCTE strategies were cost effective at
      $5,795 and $5,768 per quality-adjusted life years (QALY), respectively. In the
      microsimulation, the NFS alone and NFS/VCTE strategies were the most cost
      effective (dominant) in 66.8 and 33.2% of samples given a willingness-to-pay
      threshold of $100,000 per QALY. In a sensitivity analysis, the minimum cost per
      liver biopsy at which the NFS is cost saving is $339 and the maximum cost per
      VCTE exam at which the NFS/VCTE strategy remains cost saving is $1,593. The
      expected value of further research on this topic is $526 million. CONCLUSIONS:
      Non-invasive risk stratification with both the NFS alone and the NFS/VCTE are
      cost-effective strategies for the evaluation and management of patients with
      NAFLD presenting to a gastroenterologist. Further research is needed to better
      define the natural history of NAFLD and the effect of novel treatments on
      decision making.

PMID- 26303133
TI  - Impact of Screening Program on Incidence of Colorectal Cancer: A Cohort Study in
      Italy.
AB  - OBJECTIVES: Colorectal cancer (CRC) screening using the fecal occult blood test
      (FOBT) has been shown to be effective in reducing cause-specific mortality.
      However, although it detects pre-cancerous adenomas, it is uncertain whether FOBT
      reduces the incidence of invasive cancer. The objective is to evaluate the impact
      of screening with immunochemical FOBT (FIT) on CRC incidence and mortality.
      METHODS: An organized screening program was implemented in 2005 in the province
      of Reggio Emilia (Northern Italy). The program invites the resident population
      aged 50-69 for FIT every 2 years. Subjects who test positive are referred for
      colonoscopy. Incidence was studied through cancer registry. Person-times of
      people aged 50-74 from 1997 to 2012 were classified for exposure to screening
      according to age and period. Furthermore, two open cohorts-one never screened
      (aged 50-69 in 1997) and one invited for screening (aged 50-69 in 2005)-were
      followed up for 8 years. RESULTS: A total of 171,785 people have been invited,
      and approximately 70% have undergone FIT at least once (272,197 tests). The rate
      of colonoscopy participation has been about 90%, and 2896 cancers have been
      recorded (1237 in the screening period). The age-adjusted and sex-adjusted
      incidence rate ratios as compared with pre-screening were 1.60 (95% confidence
      interval (CI), 1.43-1.79), 0.86 (95% CI, 0.78-0.94), and 0.59 (95% CI, 0.50-0.69)
      for the first round, subsequent rounds, and post screening, respectively.
      Cumulative incidence and incidence-based mortality decreased by 10% (95% CI, 3
      17%) and 27% (95% CI, 15-37%), respectively. CONCLUSIONS: FIT screening leads to
      a decrease in the incidence of CRC and in its mortality.

PMID- 26303131
TI  - Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): Determining
      Therapeutic Goals for Treat-to-Target.
AB  - OBJECTIVES: The Selecting Therapeutic Targets in Inflammatory Bowel Disease
      (STRIDE) program was initiated by the International Organization for the Study of
      Inflammatory Bowel Diseases (IOIBD). It examined potential treatment targets for
      inflammatory bowel disease (IBD) to be used for a "treat-to-target" clinical
      management strategy using an evidence-based expert consensus process. METHODS: A
      Steering Committee of 28 IBD specialists developed recommendations based on a
      systematic literature review and expert opinion. Consensus was gained if >=75% of
      participants scored the recommendation as 7-10 on a 10-point rating scale (where
      10=agree completely). RESULTS: The group agreed upon 12 recommendations for
      ulcerative colitis (UC) and Crohn's disease (CD). The agreed target for UC was
      clinical/patient-reported outcome (PRO) remission (defined as resolution of
      rectal bleeding and diarrhea/altered bowel habit) and endoscopic remission
      (defined as a Mayo endoscopic subscore of 0-1). Histological remission was
      considered as an adjunctive goal. Clinical/PRO remission was also agreed upon as
      a target for CD and defined as resolution of abdominal pain and diarrhea/altered
      bowel habit; and endoscopic remission, defined as resolution of ulceration at
      ileocolonoscopy, or resolution of findings of inflammation on cross-sectional
      imaging in patients who cannot be adequately assessed with ileocolonoscopy.
      Biomarker remission (normal C-reactive protein (CRP) and calprotectin) was
      considered as an adjunctive target. CONCLUSIONS: Evidence- and consensus-based
      recommendations for selecting the goals for treat-to-target strategies in
      patients with IBD are made available. Prospective studies are needed to determine
      how these targets will change disease course and patients' quality of life.

PMID- 26303134
TI  - Histological Response to Fluticasone Propionate in Patients With Eosinophilic
      Esophagitis Is Associated With Improved Functional Esophageal Mucosal Integrity.
AB  - OBJECTIVES: The esophageal mucosal integrity is impaired in patients with
      eosinophilic esophagitis (EoE). We aimed to evaluate the effect of fluticasone
      propionate on inflammation and functional and structural markers of esophageal
      mucosal barrier integrity in adult patients with EoE. METHODS: In this
      prospective study, we included 15 EoE patients (median age (IQR), 43 (30-45)
      years). Patients underwent upper endoscopy before and after an 8-week course of
      swallowed fluticasone propionate 500 MUg BID. Several parameters of esophageal
      mucosal barrier integrity were evaluated: esophageal electrical tissue impedance
      in vivo during endoscopy, transepithelial electrical resistance (TER) and
      transepithelial molecule flux in Ussing chambers using esophageal biopsy
      specimens, and intercellular spaces as a structural marker of permeability using
      electron microscopy. Esophageal eosinophils and mast cells were counted, and
      expression of inflammatory cytokines and barrier integrity proteins was
      investigated using qPCR. Esophageal symptoms and signs were also assessed.
      RESULTS: Peak eosinophil and mast cell counts decreased significantly after
      fluticasone propionate treatment. The esophageal mucosal integrity increased
      substantially during treatment, as shown by increased extracellular impedance and
      TER (both P<0.01) and decreased transepithelial molecule flux in Ussing chambers
      (P<0.05). Whereas expression of genes encoding for inflammatory cytokines (IL5,
      IL13, eotaxin-3, periostin, TSLP) decreased after treatment, expression of genes
      encoding for barrier integrity proteins (filaggrin and desmoglein-1) increased.
      CONCLUSIONS: Fluticasone propionate treatment decreases eosinophilic inflammation
      and improves the esophageal mucosal barrier integrity in adult EoE patients.
      Improvement of the mucosal barrier integrity correlates with normalization of
      expression of desmoglein-1 and filaggrin marker genes.

PMID- 26303132
TI  - ACG Clinical Guideline: Diagnosis and Management of Small Bowel Bleeding.
AB  - Bleeding from the small intestine remains a relatively uncommon event, accounting
      for ~5-10% of all patients presenting with gastrointestinal (GI) bleeding. Given
      advances in small bowel imaging with video capsule endoscopy (VCE), deep
      enteroscopy, and radiographic imaging, the cause of bleeding in the small bowel
      can now be identified in most patients. The term small bowel bleeding is
      therefore proposed as a replacement for the previous classification of obscure GI
      bleeding (OGIB). We recommend that the term OGIB should be reserved for patients
      in whom a source of bleeding cannot be identified anywhere in the GI tract. A
      source of small bowel bleeding should be considered in patients with GI bleeding
      after performance of a normal upper and lower endoscopic examination. Second-look
      examinations using upper endoscopy, push enteroscopy, and/or colonoscopy can be
      performed if indicated before small bowel evaluation. VCE should be considered a
      first-line procedure for small bowel investigation. Any method of deep
      enteroscopy can be used when endoscopic evaluation and therapy are required. VCE
      should be performed before deep enteroscopy if there is no contraindication.
      Computed tomographic enterography should be performed in patients with suspected
      obstruction before VCE or after negative VCE examinations. When there is acute
      overt hemorrhage in the unstable patient, angiography should be performed
      emergently. In patients with occult hemorrhage or stable patients with active
      overt bleeding, multiphasic computed tomography should be performed after VCE or
      CTE to identify the source of bleeding and to guide further management. If a
      source of bleeding is identified in the small bowel that is associated with
      significant ongoing anemia and/or active bleeding, the patient should be managed
      with endoscopic therapy. Conservative management is recommended for patients
      without a source found after small bowel investigation, whereas repeat diagnostic
      investigations are recommended for patients with initial negative small bowel
      evaluations and ongoing overt or occult bleeding. 

PMID- 26303135
TI  - Randomized controlled trial of a home-visiting intervention on infant cognitive
      development in peri-urban South Africa.
AB  - AIM: To determine whether, in an impoverished South African community, an
      intervention that benefitted infant attachment also benefitted cognitive
      development. METHOD: Pregnant females were randomized to intervention (n=220) and
      no-treatment control groups (n=229). The intervention was home-based parenting
      support for attachment, delivered until 6 months postpartum. At 18 months,
      infants were assessed on attachment and cognitive development (Bayley Scales
      Mental Development Index [MDI]) (n=127 intervention, n=136 control participants).
      Infant MDI was examined in relation to intervention, socio-economic risk,
      antenatal depression, and infant sex and attachment. RESULTS: Overall, there was
      little effect of the intervention on MDI (p=0.094, d=0.20), but there was an
      interaction between intervention and risk (p=0.03, etap2=0.02). MDI scores of
      infants of lower risk intervention group mothers were, on average, 4.84 points
      higher than those of other infants (p=0.002, d=0.41). Antenatal depression was
      not significant once intervention and risk were controlled (p=0.08); there was no
      association between infant MDI and either sex (p=0.41) or attachment (p=0.56).
      INTERPRETATION: Parenting interventions for infant cognitive development may
      benefit from inclusion of specific components to support infant cognition beyond
      those that support attachment, and may be most effective for infants over 6
      months. They may need augmentation with other input where adversity is extreme.

PMID- 26303136
TI  - The efficiency of Poly(ADP-Ribose) Polymerase (PARP) cleavage on detection of
      apoptosis in an experimental model of testicular torsion.
AB  - The aim of this study was to evaluate the histopathological and apoptotic changes
      occurring in the rat ipsilateral and contralateral testes, after experimental
      spermatic cord torsion, and to explore and the role of poly(ADP-ribose)
      polymerase (PARP) cleavage in testicular torsion-detorsion injury. A total of 37
      Wistar albino rats were subjected to 720 degrees  unilateral spermatic cord
      torsion for 1, 2 and 4 h, followed by 4-h reperfusion, or else to a sham
      operation (control group). Histology of the testicle was evaluated using
      haematoxylin-eosin (H&E) staining and Johnsen's scoring system. Germ cell
      apoptosis was evaluated via active caspase-3 immunostaining, and PARP expression
      levels were evaluated via Western blotting. The mean Johnsen's tubular biopsy
      scores (JTBS) of the ipsilateral testicles were lower for all torsion groups than
      for the controls (P < 0.05), but the JTBS of the contralateral testicles were
      only lower in the 4-h torsion group (P < 0.05). The mean apoptosis score (AS) of
      the ipsilateral and contralateral testicles was significantly higher in the
      torsion groups than in the sham group. AS increased correlatively with torsion
      time, in both testicles. The effect of testicular torsion on PARP cleavage was
      time dependent, with the highest effect observed after 4 h of testicular torsion
      (P < 0.05). Testicular torsion caused time-dependent histological changes,
      apoptosis and increases in PARP cleavage. Our results suggest that testicular
      torsion-detorsion injury caused cell damage and germ cell apoptosis that
      apparently involved cleavage of PARP. Increased PARP cleavage could, in turn,
      lead to enhanced apoptosis.

PMID- 26303137
TI  - Identification and molecular characterization of a novel duck Tembusu virus
      isolate from Southwest China.
AB  - Tembusu virus (TMUV) has caused significant economic losses in the Chinese duck
      industry and may have been overlooked regarding its zoonotic transmission
      potential. A novel TMUV isolate (named CQW1) was separated from the liver tissue
      of a young duck in Southwest China. The CQW1 isolate proliferated in embryonated
      duck eggs and led to death within 3-4 days post-inoculation. Furthermore, CQW1
      replicated in duck embryo fibroblast (DEF) cells and caused a cytopathic effect
      (CPE). The disease emerged on a duck farm in Southwest China and was reproduced
      by animal experiment. We found that CQW1 was detectable by RT-PCR in brain and
      liver tissues of dead ducklings within 5 days after inoculation. Most
      importantly, concentrated nuclei, neuronophagia and microglial nodules were
      observed in the brain tissue of the inoculated ducklings, and additionally, the
      liver tissue was affected, mainly by disordered lobular architecture,
      degeneration, necrosis and regenerated hepatocytes. Analysis of the complete
      genome sequence showed that CQW1 was 10,992 nt in length with two nucleotide
      insertions and shared 96.8% to 99.1% and 98.4% to 99.6% identity at nucleotide
      and amino acid level, respectively, with Chinese isolates. Phylogenetic analysis
      of the nucleotide sequences demonstrated that the CQW1 isolate was closely
      related to other members of the genus Flavivirus and formed a new clade together
      with the GX2013H isolate. Also, the CQW1 isolate demonstrated the highest average
      pairwise distance value among the Chinese isolates. In the present study, we
      obtained evidence that TMUV is present in Southwest China. Extensive pathological
      and epidemiological studies are urgently needed.

PMID- 26303138
TI  - Lineage distribution and E2 sequence variation of high-risk human papillomavirus
      types isolated from patients with cervical cancer in Sichuan province, China.
AB  - To explore the nucleotide sequence variability of the E2 gene in high-risk HPV
      types in cervical cancer patients from Sichuan province, China, the E2 genes of
      eight high-risk HPV types were amplified and sequenced. Several novel nucleotide
      substitutions and deletions were observed. The lineages to which the isolates
      belonged were determined by phylogenetic analysis, employing the sequence of the
      representative lineages/sublineages in the coherent classification and
      nomenclature system as references. This study updates the lineage distribution
      data on high-risk HPV types in Southwest China and helps broaden understanding of
      the polymorphism of the E2 gene. 

PMID- 26303139
TI  - Swine and rabbits are the main reservoirs of hepatitis E virus in China:
      detection of HEV RNA in feces of farmed and wild animals.
AB  - Hepatitis E virus (HEV) infection is recognized as a zoonosis. The prevalence of
      HEV RNA and anti-HEV antibodies in many animal species has been reported, but the
      host range of HEV is unclear. The aims of this study were to investigate HEV
      infection in various animal species and to determine the reservoirs of HEV. Eight
      hundred twenty-two fecal samples from 17 mammal species and 67 fecal samples from
      24 avian species were collected in China and tested for HEV RNA by RT-nPCR. The
      products of PCR were sequenced and analyzed phylogenetically. The positive rates
      of HEV RNA isolated from pigs in Beijing, Shandong, and Henan were 33%, 30%, and
      92%, respectively, and that from rabbits in Beijing was 5%. HEV RNA was not
      detectable in farmed foxes, sheep or sika deer, or in wild animals in zoos,
      including wild boars, yaks, camels, Asiatic black bears, African lions, red
      pandas, civets, wolves, jackals and primates. Sequence analysis revealed that
      swine isolates had 97.8%-98.4% nucleotide sequence identity to genotype 4d
      isolates from patients in Shandong and Jiangsu of China. Phylogenetic analysis
      showed that swine HEV isolates belong to genotype 4, including subgenotype 4h in
      Henan and 4d in Beijing and Shandong. The rabbit HEV strains shared 93%-99%
      nucleotide sequence identity with rabbit strains isolated from Inner Mongolia. In
      conclusion, swine and rabbits have been confirmed to be the main reservoirs of
      HEV in China.

PMID- 26303140
TI  - Understanding the Metal Distribution in Core-Shell Nanoparticles Prepared in
      Micellar Media.
AB  - The factors that govern the reaction rate of Au/Pt bimetallic nanoparticles
      prepared in microemulsions by a one-pot method are examined in the light of a
      simulation model. Kinetic analysis proves that the intermicellar exchange has a
      strong effect on the reaction rates of the metal precursors. Relating to Au,
      reaction rate is controlled by the intermicellar exchange rate whenever
      concentration is high enough. With respect to Pt, the combination of a slower
      reduction rate and the confinement of the reactants inside micelles gives rise to
      an increase of local Pt salt concentration. Two main consequences must be
      emphasized: On one hand, Pt reduction may continue independently whether or not a
      new intermicellar exchange takes place. On the other hand, the accumulation of Pt
      reactants accelerates the reaction. As the reactant accumulation is larger when
      the exchange rate is faster, the resulting Pt rate increases. This results in a
      minor difference in the reduction rate of both metals. This difference is
      reflected in the metal distribution of the bimetallic nanoparticle, which shows a
      greater degree of mixture as the intermicellar exchange rate is faster. 

PMID- 26303141
TI  - GaAs-Based Superluminescent Light-Emitting Diodes with 290-nm Emission Bandwidth
      by Using Hybrid Quantum Well/Quantum Dot Structures.
AB  - A high-performance superluminescent light-emitting diode (SLD) based upon a
      hybrid quantum well (QW)/quantum dot (QD) active element is reported and is
      assessed with regard to the resolution obtainable in an optical coherence
      tomography system. We report on the appearance of strong emission from higher
      order optical transition from the QW in a hybrid QW/QD structure. This additional
      emission broadening method contributes significantly to obtaining a 3-dB
      linewidth of 290 nm centered at 1200 nm, with 2.4 mW at room temperature. 

PMID- 26303143
TI  - Long-Term Administration of Neuropeptide Y in the Subcutaneous Infusion Results
      in Cardiac Dysfunction and Hypertrophy in Rats.
AB  - BACKGROUND/AIMS: The purpose of the present study was to clarify whether
      chronically elevated plasma neuropeptide Y (NPY) might affect heart function and
      cardiac remodeling in rats. METHODS: Male Wistar rats were administered NPY (85
      MUg for 30 days) by mini-osmotic pump subcutaneously implanted between the
      scapulae. Associated indices for heart function, cardiac remodeling and
      hypertrophy were evaluated. RESULTS: Compared to the sham group, the baseline
      systolic blood pressure (SBP) in rats administered NPY was significantly
      increased; cardiac function was significantly decreased, as indicated by reduced
      ejection fraction (EF), left ventricular end-systolic pressure (LVESP), maximum
      change velocity of left ventricular pressure in the isovolumic contraction or
      relaxation period (+/- dp/dtmax) and increased left ventricular end-diastolic
      pressure (LVEDP); hematoxylin-eosin (H&E) staining detection displayed enlarged
      cell areas and a consistent increase in heart-to-body weight ratios (HW/BW) was
      observed; quantitative real time PCR (qRT-PCR) and Western blot analysis showed
      markedly increased expressions of beta-myosin heavy chain (beta-MHC), calcineurin
      (CaN) and phosphorylated p38 proteins, while no changes were found in the
      expressions of p38 total protein and the phosphorylations of JNK and ERK.
      CONCLUSION: This study reported for the first time that long-term elevated plasma
      concentration of NPY could induce cardiac dysfunction and cardiac hypertrophy and
      this phenomenon could, in part, be mediated by the Ca2+/CaM-dependent CaN pathway
      and p38 mitogen-activated protein kinase (MAPK) signal pathway in rats.

PMID- 26303144
TI  - G protein-coupled receptor 26 immunoreactivity in intranuclear inclusions
      associated with polyglutamine and intranuclear inclusion body diseases.
AB  - G protein-coupled receptor 26 (GPR26) is one of the G-protein-coupled receptors
      (GPCRs), which comprise the largest family of membrane proteins and mediate most
      of the physiological responses to hormones, neurotransmitters and environmental
      stimulants. Although GPCRs are considered to play an important role in the
      pathophysiology of neurodegenerative disorders, it is uncertain whether GPR26 is
      involved in the pathogenesis of polyglutamine and intranuclear inclusion body
      diseases. We immunohistochemically examined the brain tissues of patients with
      four polyglutamine diseases (Huntington's disease, dentatorubral-pallidoluysian
      atrophy, and spinocerebellar ataxia types 1 and 3) and intranuclear inclusion
      body disease, and normal control subjects. In controls, anti-GPR26 antibody
      immunolabeled the neuronal cytoplasm in a diffuse granular pattern. Neuronal
      nuclear inclusions in polyglutamine diseases were immunopositive for GPR26. In
      intranuclear inclusion body disease, GPR26-positive nuclear inclusions were found
      in both neurons and glial cells. Marinesco bodies in aged control subjects were
      also positive for GPR26. Double immunofluorescence analysis revealed co
      localization of GPR26 with polyglutamine or ubiquitin in these nuclear
      inclusions. These findings suggest that GPR26 may have a common role in the
      formation or degradation of intranuclear inclusions in several neurodegenerative
      diseases. 

PMID- 26303142
TI  - Up-regulation of steroid biosynthesis by retinoid signaling: Implications for
      aging.
AB  - Retinoids (vitamin A and its derivatives) are critical for a spectrum of
      developmental and physiological processes, in which steroid hormones also play
      indispensable roles. The StAR protein predominantly regulates steroid
      biosynthesis in steroidogenic tissues. We have reported that regulation of
      retinoid, especially atRA and 9-cis RA, responsive StAR transcription is largely
      mediated by an LXR-RXR/RAR heterodimeric motif in the mouse StAR promoter. Herein
      we demonstrate that retinoids are capable of enhancing StAR protein, P-StAR, and
      steroid production in granulosa, adrenocortical, glial, and epidermal cells.
      Whereas transient expression of RARalpha and RXRalpha enhanced 9-cis RA induced
      StAR gene transcription, silencing of RXRalpha with siRNA, decreased StAR and
      steroid levels. An oligonucleotide probe encompassing an LXR-RXR/RAR motif bound
      to adrenocortical and epidermal keratinocyte nuclear proteins in EMSAs. ChIP
      studies revealed association of RARalpha and RXRalpha with the StAR proximal
      promoter. Further studies demonstrated that StAR mRNA levels decreased in
      diseased and elderly men and women skin tissues and that atRA could restore
      steroidogenesis in epidermal keratinocytes of aged individuals. These findings
      provide novel insights into the relevance of retinoid signaling in the up
      regulation of steroid biosynthesis in various target tissues, and indicate that
      retinoid therapy may have important implications in age-related complications and
      diseases. 

PMID- 26303145
TI  - Effects of chronic dietary exposure to monosodium glutamate on feeding behavior,
      adiposity, gastrointestinal motility, and cardiovascular function in healthy
      adult rats.
AB  - BACKGROUND: Monosodium glutamate (MSG) is a flavor-enhancer widely used as a food
      additive. However, its safe dietary concentration and its toxicity, including its
      possible implication in the recent metabolic syndrome pandemia, is still a
      controversial issue. Therefore, a deep knowledge of its effects upon regular
      dietary use is needed. Our aim was to evaluate the effects of chronic exposure to
      MSG on feeding behavior, abdominal fat, gastrointestinal motility, and
      cardiovascular function in rats. METHODS: Two groups of adult male Wistar rats
      were used: control and treated with MSG (4 g/L in drinking water) for 6 weeks.
      Different functional parameters were determined and the histological structure
      was analyzed in tissues of interest. KEY RESULTS: Compared to control animals,
      chronic MSG increased water intake but did not modify food ingestion or body
      weight gain. Neither the abdominal fat volume nor the fat fraction, measured by
      magnetic resonance imaging, was modified by MSG. Monosodium glutamate did not
      alter general gastrointestinal motility, but significantly increased the colonic
      response to mechanical stimulation. It slightly reduced endothelium-dependent
      relaxation in aorta, without significantly modifying any other cardiovascular
      parameters. No significant histological alterations were detected in salivary
      glands, intestinal wall, aorta, heart, and kidney. CONCLUSIONS & INFERENCES:
      Chronic treatment with MSG in the adult rat increased water intake. This supports
      its potential to improve acceptance of low-fat regimens and to increase hydration
      in the elderly and sportspeople, often at risk of dehydration. Changes in colonic
      contractility and cardiovascular function could have some long-term repercussions
      warranting further research.

PMID- 26303146
TI  - Matrix Metalloproteinase-9 (279R/Q) Polymorphism is Associated with Clinical
      Severity and Airflow Limitation in Tunisian Patients with Chronic Obstructive
      Pulmonary Disease.
AB  - BACKGROUND: The aim of this study was to investigate the role of matrix
      metalloproteinase-9 (MMP-9) C-1562T and 279R/Q (836G>A) polymorphisms in the
      development of chronic obstructive pulmonary disease (COPD) in Tunisians and to
      determine their impact on disease progression and airflow obstruction. METHODS:
      Pulmonary functional tests were evaluated by body plethysmography. MMP-9
      genotypes were determined in patients with COPD (n = 138) and healthy controls (n
      = 216) by polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP). Serum MMP-9 and interleukin-6 (IL-6) levels were determined by enzyme
      linked immunosorbent assays (ELISA) and activity of MMP-9 was evaluated by
      gelatin zymography. RESULTS: No significant association was found between genetic
      variations in MMP-9 C-1562T and 279R/Q polymorphisms and the risk of development
      of COPD. However, a significant correlation was retrieved between the 279 R/Q
      polymorphism and disease severity (P = 0.02). In addition, homozygous Q (A)
      genotype was associated with a poorer lung function with a fall in forced
      expiratory volume in 1 s (FEV1) (%) and forced vital capacity (FVC%) among COPD
      patients compared with both AG and GG individuals (52.06 +/- 19.6 vs. 59.08 +/-
      17.19, P = 0.03 and 72.41 +/- 21.42 vs. 82.98 +/- 16.48, P = 0.002,
      respectively). Using ELISA, a higher level of MMP-9 was found in patients with
      the CT genotype (P = 0.03), while no significant impact of the 279R/Q
      polymorphism was observed (P = 0.48). In contrast, by using zymography gel
      analysis, MMP-9 activity was enhanced in individuals carrying the R(G) allele in
      comparison with those homozygous for the Q(A) variant (P = 0.02). CONCLUSION: Our
      results support a role for the 279R/Q polymorphism in physiological alterations
      that may affect progression and severity of COPD. These findings could be related
      to the decreased activity of MMP-9 among COPD patients carrying the 279Q variant.

PMID- 26303147
TI  - Hydromonas duriensis gen. nov., sp. nov., isolated from freshwater.
AB  - An aerobic, Gram-stain-negative rod, designated strain A2P5T, was isolated from
      the Douro river, in Porto, Portugal. Cells were catalase- and oxidase-positive.
      Growth occurred at 15-30  degrees C, at pH 6-8 and in the presence of 1 % (w/v)
      NaCl. The major respiratory quinone was Q8, the genomic DNA had a G+C content of
      47 +/- 1 mol%, and phosphatidylethanolamine, phosphatidylglycerol and
      diphosphatidylglycerol were amongst the major polar lipids. On the basis of 16S
      rRNA gene sequence analysis, strain A2P5T was observed to be a member of the
      family Burkholderiaceae, but could not be identified as a member of any validly
      named genus. The low levels of 16S rRNA gene sequence similarity to other
      recognized taxa ( < 91 %), together with the comparative analysis of phenotypic
      and chemotaxonomic characteristics, supported the proposal of a novel species of
      a new genus within the family Burkholderiaceae. The name Hydromonas duriensis
      gen. nov., sp. nov. is proposed. The type strain of Hydromonas duriensis is A2P5T
      ( = LMG 28428T = CCUG 66137T).

PMID- 26303148
TI  - Skeletal muscle metaboreflex in patients with chronic renal failure.
AB  - The sympathetic nervous system is affected in patients with chronic renal failure
      (CRF). This study tested the hypothesis that patients with CRF have an altered
      skeletal muscle metaboreflex. Twenty patients with CRF and 18 healthy subjects of
      similar age participated in the study. The muscle metaboreflex was determined
      based on heart rate (HR), mean arterial pressure, calf blood flow and calf
      vascular resistance (CVR) in response to handgrip exercise. The control of
      vascular resistance in the calf muscle mediated by the metaboreflex was estimated
      by subtracting the area under the curve with circulatory occlusion from that
      without occlusion. Arterial pressure and HR responses during exercise and
      recovery were similar in two groups of subjects. In the control group, CVR
      increased during exercise and remained elevated during circulatory occlusion,
      whereas no significant change was seen in the patients. Thus, the index of the
      metaboreflex was 7.82 +/- 9.57 in the patients versus16.52 +/- 14 units in the
      controls. The findings demonstrate that patients with CRF have a decreased
      vascular resistance response in the calf during the handgrip exercise, which
      suggests that CRF condition attenuates this reflex.

PMID- 26303149
TI  - Reduction in orthopaedic surgery in patients with rheumatoid arthritis: a
      Norwegian register-based study.
AB  - OBJECTIVES: The disease course of patients with rheumatoid arthritis (RA) has
      become milder in recent years. In this study we investigated the incidence of
      orthopaedic surgery in patients with RA. METHOD: From the Norwegian Arthroplasty
      Register we selected joint replacement procedures conducted during the years 1994
      2012 (n = 11 337), and from the Norwegian Patient Register we obtained data on
      synovectomies (n = 4782) and arthrodeses (n = 6022) during 1997-2012. Using
      Poisson regression we analysed the time trends in the incidence of procedures
      performed. RESULTS: There was a significant decrease in the incidence of
      arthroplasty surgery (coefficient of -0.050 per year) and synovectomies
      (coefficient of -0.10) and a declining trend of arthrodeses in patients with RA
      in the study periods. The greatest reduction was found in procedures involving
      the wrist and hand. CONCLUSIONS: We found a decrease in orthopaedic surgery in
      patients with RA that continued into the biologic era and throughout the study
      period. The general increasing trend in the use of synthetic and biological
      disease-modifying anti-rheumatic drugs (DMARDs) thus coincides with less joint
      destruction and an improved long-term prognosis of patients with RA.

PMID- 26303151
TI  - Real-Time Statistical Modeling of Blood Sugar.
AB  - Diabetes is considered a chronic disease that incurs various types of cost to the
      world. One major challenge in the control of Diabetes is the real time
      determination of the proper insulin dose. In this paper, we develop a prototype
      for real time blood sugar control, integrated with the cloud. Our system controls
      blood sugar by observing the blood sugar level and accordingly determining the
      appropriate insulin dose based on patient's historical data, all in real time and
      automatically. To determine the appropriate insulin dose, we propose two
      statistical models for modeling blood sugar profiles, namely ARIMA and Markov
      based model. Our experiment used to evaluate the performance of the two models
      shows that the ARIMA model outperforms the Markov-based model in terms of
      prediction accuracy. 

PMID- 26303150
TI  - Clinically important drug-drug interactions in poly-treated elderly outpatients:
      a campaign to improve appropriateness in general practice.
AB  - AIMS: The aim was to assess the impact of a campaign for general practitioners
      (GPs) to reduce clinically-important drug-drug interactions (DDIs) in poly
      treated elderly patients. METHODS: We compiled a list of 53 DDIs and analyzed
      reimbursed prescriptions dispensed to poly-treated (>=four drugs) elderly (>65
      years) patients in the Emilia Romagna region during January 2011-June 2011 (first
      pre-intervention period), January 2012-June 2012 (second pre-intervention period)
      and January 2013-June 2013 (post-intervention period). Educational initiatives to
      GPs were completed in July 2012-December 2012. Pre-test/post-test analysis (2013
      vs. 2012) was performed, also using predicted 2013 data (P < 0.01 for statistical
      significance). RESULTS: Despite the slight increase in poly-therapy rate (16% in
      2013, +1.5% from 2011), we found a stable or slightly declining number of
      potential DDIs for each elderly poly-treated patient (~1.5). In 2013, 11 DDIs
      exceeded 5% of prevalence rate: antidiabetics-beta-adrenoceptor blockers ranked
      first (20.3%), followed by ACE Inhibitors (ACEIs)/sartans-non steroidal anti
      inflammatory drugs (NSAIDs) (16.4%), diuretics-NSAIDs (13.6%), selective
      serotonin re-uptake inhibitors (SSRIs)-NSAIDs/acetyl salicylic acid (ASA) (12.7%)
      and corticosteroids-NSAIDs/ASA (9.7%). A remarkable reduction emerged for NSAID
      related DDIs (diuretics-NSAIDs peaked -14.5%; P < 0.01), whereas prevalence of
      antidiabetics-beta-adrenoceptor blockers increased (+7.9%; P < 0.01). When using
      predicted values, the statistical significance disappeared for antidiabetics-beta
      adrenoceptor blockers (+1.3%; P = 0.04), whereas it persisted for almost all
      NSAIDs-related DDIs: ACEIs/sartans-NSAIDs (-3.0%), diuretics-NSAIDs (-6.0%),
      SSRIs-NSAIDs/ASA (-5.9%). CONCLUSIONS: This campaign contained the burden of DDIs
      in poly-treated elderly patients by 1) reducing most prevalent DDIs, especially
      NSAIDs-related DDIs and 2) balancing the observed rise in poly-therapy rate with
      stable rate in overall prescriptions of potentially interacting drugs per
      patient.

PMID- 26303152
TI  - Mobile Applications for Type 2 Diabetes Risk Estimation: a Systematic Review.
AB  - Screening for chronical diseases like type 2 diabetes can be done using different
      methods and various risk tests. This study present a review of type 2 diabetes
      risk estimation mobile applications focusing on their functionality and
      availability of information on the underlying risk calculators. Only 9 out of 31
      reviewed mobile applications, featured in three major mobile application stores,
      disclosed the name of risk calculator used for assessing the risk of type 2
      diabetes. Even more concerning, none of the reviewed applications mentioned that
      they are collecting the data from users to improve the performance of their risk
      estimation calculators or offer users the descriptive statistics of the results
      from users that already used the application. For that purpose the questionnaires
      used for calculation of risk should be upgraded by including the information on
      the most recent blood sugar level measurements from users. Although mobile
      applications represent a great future potential for health applications,
      developers still do not put enough emphasis on informing the user of the
      underlying methods used to estimate the risk for a specific clinical condition. 

PMID- 26303153
TI  - Comparative effectiveness of cardiac implantable electrical devices.

PMID- 26303154
TI  - Should the patients with thyroid nodule who had benign fine-needle aspiration
      biopsy findings and suspicious ultrasonographic and clinical findings undergo
      surgery?

PMID- 26303155
TI  - Margaret McCartney: Nagging people is a futile exercise.

PMID- 26303156
TI  - Sample size considerations for split-mouth design.
AB  - Split-mouth designs are frequently used in dental clinical research, where a
      mouth is divided into two or more experimental segments that are randomly
      assigned to different treatments. It has the distinct advantage of removing a lot
      of inter-subject variability from the estimated treatment effect. Methods of
      statistical analyses for split-mouth design have been well developed. However,
      little work is available on sample size consideration at the design phase of a
      split-mouth trial, although many researchers pointed out that the split-mouth
      design can only be more efficient than a parallel-group design when within
      subject correlation coefficient is substantial. In this paper, we propose to use
      the generalized estimating equation (GEE) approach to assess treatment effect in
      split-mouth trials, accounting for correlations among observations. Closed-form
      sample size formulas are introduced for the split-mouth design with continuous
      and binary outcomes, assuming exchangeable and "nested exchangeable" correlation
      structures for outcomes from the same subject. The statistical inference is based
      on the large sample approximation under the GEE approach. Simulation studies are
      conducted to investigate the finite-sample performance of the GEE sample size
      formulas. A dental clinical trial example is presented for illustration.

PMID- 26303157
TI  - Transformation of health-care and legal systems for the transgender population:
      The need for change in Australia.

PMID- 26303158
TI  - Fasting Lipoprotein Lipase Protein Levels Can Predict a Postmeal Increment of
      Triglyceride Levels in Fasting Normohypertriglyceridemic Subjects.
AB  - BACKGROUND: Although a postprandial increment in triglyceride (TG) levels is
      considered to be a risk factor for atherogenesis, tests (e.g., fat load) to
      assess postprandial changes in TG levels cannot be easily applied to clinical
      practice. Therefore, fasting markers that predict postprandial TG states are
      needed to be developed. One current candidate is lipoprotein lipase (LPL)
      protein, a molecule that hydrides TGs. This study investigated whether fasting
      LPL levels could predict postprandial TG levels. METHODS: A total of 17 subjects
      (11 men, 6 women, mean age 52 +/- 11 years) with normotriglyceridemia during
      fasting underwent the meal test. Several fasting parameters, including LPL, were
      measured for the area under the curve of postprandial TGs (AUC-TG). RESULTS: The
      subjects' mean fasting TG level was 1.30 mmol/l, and their mean LPL level was
      41.6 ng/ml. The subjects' TG levels increased after loading (they peaked after
      two postprandial hours). Stepwise multiple regression analysis demonstrated that
      fasting TG levels were a predictor of the AUC-TG. In addition, fasting LPL mass
      levels were found to be a predictor of the AUC-TG (beta = 0.65, P < 0.01), and
      this relationship was independent of fasting TG levels. CONCLUSION: Fasting LPL
      levels may be useful to predict postprandial TG increment in this population.

PMID- 26303159
TI  - Associations between intimate partner violence, childcare practices and infant
      health: findings from Demographic and Health Surveys in Bolivia, Colombia and
      Peru.
AB  - BACKGROUND: Child health is significantly poorer in homes with intimate partner
      violence (IPV). However, a possible link to parental provision of childcare has
      been neglected. METHODS: Utilizing data from Demographic and Health Surveys, this
      study examined the association between IPV and illness signs in children 0-59
      months in Bolivia (n = 3586), Colombia (n = 9955) and Peru (n = 6260), taking
      into account socio-demographic factors, childcare and severe child physical
      punishment. Data were collected in the years 2008, 2010 and 2012 for Bolivia,
      Colombia and Peru respectively. RESULTS: The study found weak but persistent
      effects of IPV on illness signs in Bolivia (OR 1.37, 95% CI 1.14-1.63) and Peru
      (OR 1.49, 95% CI 1.26-1.77), after adjusting for the effects of childcare. These
      effects were not observed in Colombia. CONCLUSIONS: The results call for a mix of
      qualitative and quantitative research that can map direct, mediating and
      moderating patterns of relationships between IPV, childcare practices and child
      health. Can good childcare mitigate the negative effects of IPV? Can poor
      childcare exacerbate the negative effects of IPV? Such interactions were not
      observed in the present study, but should be the focus of much more intensive
      investigation, to help inform child health promotion. Answers could lead to
      better interventions to improve child health, and perhaps to tackle IPV.

PMID- 26303160
TI  - Role of initial system-bath correlation on coherence trapping.
AB  - We study the coherence trapping of a qubit correlated initially with a non
      Markovian bath in a pure dephasing channel. By considering the initial qubit-bath
      correlation and the bath spectral density, we find that the initial qubit-bath
      correlation can lead to a more efficient coherence trapping than that of the
      initially separable qubit-bath state. The stationary coherence in the long time
      limit can be maximized by optimizing the parameters of the initially correlated
      qubit-bath state and the bath spectral density. In addition, the effects of this
      initial correlation on the maximal evolution speed for the qubit trapped to its
      stationary coherence state are also explored. 

PMID- 26303163
TI  - Reproductive and Developmental Toxicity of Orally Administered Botanical
      Composition, UP446-Part I: Effects on Embryo-Fetal Development in New Zealand
      White Rabbits and Sprague Dawley Rats.
AB  - The pharmacotoxicology impacts of dietary supplements taken at the time of
      pregnancy have remained alarming since women are the frequent herbal medicine
      users in many countries as a complement to the conventional pregnancy management.
      The use of herbal medicines and diet supplements in expectant mothers linked
      closely to the health of the childbearing mothers and the fetuses where the lack
      of developmental safety data imposes a challenge to make the right choices. Here,
      we describe the potential adverse effects of UP446, a standardized bioflavonoid
      composition from the roots of Scutellaria baicalensis and the heartwoods of
      Acacia catechu, on embryo-fetal development following maternal exposure during
      the critical period of major organogenesis in rabbits and rats. Pregnant dams
      were treated orally with UP446 at doses of 250, 500, and 1000 mg/kg/day during
      gestation. The number of resorptions, implantations, litter size, body weights,
      and skeletal development was evaluated. Maternal food intake and body, tissue,
      and placenta weight were also assessed. There were no statistically significant
      differences in implantation, congenital malformation, embryo-fetal mortalities,
      and fetuses sex ratios in all dosing groups of both species. Therefore, the no
      observed adverse effect level of UP446 was considered to be greater than 1000
      mg/kg in both the maternal and fetus in both species. 

PMID- 26303162
TI  - Tolerability and safety of weekly primaquine against relapse of Plasmodium vivax
      in Cambodians with glucose-6-phosphate dehydrogenase deficiency.
AB  - BACKGROUND: Primaquine is used to prevent Plasmodium vivax relapse; however, it
      is not implemented in many malaria-endemic countries, including Cambodia, for
      fear of precipitating primaquine-induced acute haemolytic anaemia in patients
      with glucose-6-phosphate dehydrogenase deficiency (G6PDd). Reluctance to use
      primaquine is reinforced by a lack of quality safety data. This study was
      conducted to assess the tolerability of a primaquine regimen in Cambodian
      severely deficient G6PD variants to ascertain whether a weekly primaquine could
      be given without testing for G6PDd. METHODS: From January 2013 to January 2014,
      Cambodians with acute vivax malaria were treated with
      dihydroartemisinin/piperaquine on days (D) 0, 1 and 2 with weekly doses of
      primaquine 0.75 mg/kg for 8 weeks (starting on D0, last dose on D49), and
      followed until D56. Participants' G6PD status was confirmed by G6PD genotype and
      measured G6PD activity. The primary outcome was treatment completion without
      primaquine toxicity defined as any one of: (1) severe anaemia (haemoglobin [Hb]
      <7 g/dL), (2) a >25 % fractional fall in Hb from D0, (3) the need for a blood
      transfusion, (4) haemoglobinuria, (5) acute kidney injury (an increase in
      baseline serum creatinine >50 %) or (6) methaemoglobinaemia >20 %. RESULTS: We
      enrolled 75 patients with a median age of 24 years (range 5-63); 63 patients (84
      %) were male. Eighteen patients were G6PDd (17/18 had the Viangchan variant) and
      had D0 G6PD activity ranging from 0.1 to 1.5 U/g Hb (median 0.85 U/g Hb). In the
      57 patients with normal G6PD (G6PDn), D0 G6PD activity ranged from 6.9 to 18.5
      U/g Hb (median 12 U/g Hb). Median D0 Hb concentrations were similar (P = 0.46)
      between G6PDd (13 g/dL, range 9.6-16) and G6PDn (13.5 g/dL, range 9-16.3) and
      reached a nadir on D2 in both groups: 10.8 g/dL (8.2-15.3) versus 12.4 g/dL (8.8
      15.2) (P = 0.006), respectively. By D7, five G6PDd patients (27.7 %) had a >25 %
      fall in Hb, compared to 0 G6PDn patients (P = 0.00049). One of these G6PDd
      patients required a blood transfusion (D0-D5 Hb, 10.0-7.2 g/dL). No patients
      developed severe anaemia, haemoglobinuria, a methaemoglobin concentration >4.9 %,
      or acute kidney injury. CONCLUSIONS: Vivax-infected G6PDd Cambodian patients
      demonstrated significant, mostly transient, falls in Hb and one received a blood
      transfusion. Weekly primaquine in G6PDd patients mandates medical supervision and
      pre-treatment screening for G6PD status. The feasibility of implementing a
      package of G6PDd testing and supervised primaquine should be explored. TRIAL
      REGISTRATION: The trial was registered on 3/1/2013 and the registration number is
      ACTRN12613000003774.

PMID- 26303164
TI  - High Glucose Represses hERG K+ Channel Expression through Trafficking Inhibition.
AB  - BACKGROUND/AIMS: Abnormal QT prolongation is the most prominent cardiac
      electrical disturbance in patients with diabetes mellitus (DM). It is well known
      that the human ether-ago-go-related gene (hERG) controls the rapid delayed
      rectifier K+ current (IKr) in cardiac cells. The expression of the hERG channel
      is severely down-regulated in diabetic hearts, and this down-regulation is a
      critical contributor to the slowing of repolarization and QT prolongation.
      However, the intracellular mechanisms underlying the diabetes-induced hERG
      deficiency remain unknown. METHODS: The expression of the hERG channel was
      assessed via western blot analysis, and the hERG current was detected with a
      patch-clamp technique. RESULTS: The results of our study revealed that the
      expression of the hERG protein and the hERG current were substantially decreased
      in high-glucose-treated hERG-HEK cells. Moreover, we demonstrated that the high
      glucose-mediated damage to the hERG channel depended on the down-regulation of
      protein levels but not the alteration of channel kinetics. These discoveries
      indicated that high glucose likely disrupted hERG channel trafficking. From the
      western blot and immunoprecipitation analyses, we found that high glucose induced
      trafficking inhibition through an effect on the expression of Hsp90 and its
      interaction with hERG. Furthermore, the high-glucose-induced inhibition of hERG
      channel trafficking could activate the unfolded protein response (UPR) by up
      regulating the expression levels of activating transcription factor-6 (ATF-6) and
      the ER chaperone protein calnexin. In addition, we demonstrated that 100 nM
      insulin up-regulated the expression of the hERG channel and rescued the hERG
      channel repression caused by high glucose. CONCLUSION: The results of our study
      provide the first evidence of a high-glucose-induced hERG channel deficiency
      resulting from the inhibition of channel trafficking. Furthermore, insulin
      promotes the expression of the hERG channel and ameliorates the high-glucose
      induced inhibition of the hERG channel.

PMID- 26303165
TI  - Structure and conformations of 2-substituted and 3-substituted alumolanes in
      polar solvents: a direct NMR observation.

PMID- 26303166
TI  - An MRI-compatible loading device to assess knee joint cartilage deformation:
      Effect of preloading and inter-test repeatability.
AB  - It has been suggested that the extent and location of cartilage deformation
      within a joint under compressive loading may be predictive of predisposition to
      further degeneration. To explore this relationship in detail requires the
      quantification of cartilage deformation under controlled loads on a per-patient
      basis in a longitudinal manner. Our objectives were (1) to design a device
      capable of applying controllable axial loads while ensuring repeatable within
      patient tibiofemoral positioning during magnetic resonance imaging (MRI) scans
      and (2) to determine the duration for which load should be maintained prior to
      the image acquisition, for a reproducible measurement of cartilage deformation,
      within the restraints of a clinical setting. A displacement control loading
      device was manufactured from MRI-compatible materials and tested on four
      volunteers for the following five scans: an unloaded scan, two repeat immediate
      scans which were started immediately after the application of 50% body weight,
      and two repeat delayed scans started 12 min after load application. Outcome
      measures included within-patient changes in tibiofemoral position and cartilage
      deformation between repeat loaded scans. The differences in tibiofemoral position
      between repeat loaded scans were <1mm in translation and <2 degrees  in rotation.
      Cartilage deformations were more consistent in the delayed scans compared to the
      immediate scans. We conclude that our loading device can ensure repeatable
      tibiofemoral positioning to allow for longitudinal studies, and the delayed scan
      may enable us to obtain more reproducible measurements of cartilage deformation
      in a clinical setting.

PMID- 26303167
TI  - A new coordination pattern classification to assess gait kinematics when
      utilising a modified vector coding technique.
AB  - A modified vector coding (VC) technique was used to quantify lumbar-pelvic
      coordination during gait. The outcome measure from the modified VC technique is
      known as the coupling angle (CA) which can be classified into one of four
      coordination patterns. This study introduces a new classification for this
      coordination pattern that expands on a current data analysis technique by
      introducing the terms in-phase with proximal dominancy, in-phase with distal
      dominancy, anti-phase with proximal dominancy and anti-phase with distal
      dominancy. This proposed coordination pattern classification can offer an
      interpretation of the CA that provides either in-phase or anti-phase coordination
      information, along with an understanding of the direction of segmental rotations
      and the segment that is the dominant mover at each point in time. Classifying the
      CA against the new defined coordination patterns and presenting this information
      in a traditional time-series format in this study has offered an insight into
      segmental range of motion. A new illustration is also presented which details the
      distribution of the CA within each of the coordination patterns and allows for
      the quantification of segmental dominancy. The proposed illustration technique
      can have important implications in demonstrating gait coordination data in an
      easily comprehensible fashion by clinicians and scientists alike. 

PMID- 26303168
TI  - Damage-induced hydrolyses modelling of biodegradable polymers for tendons and
      ligaments repair.
AB  - The use of biodegradable synthetic grafts to repair injured ligaments may
      overcome the disadvantages of other solutions. Apart from biological
      compatibility, these devices shall also be functionally compatible and
      temporarily displayed, during the healing process, adequate mechanical support.
      Laxity of these devices is an important concern. This can cause failure since it
      may result in joint instability. Laxity results from a progressive accumulation
      of plastic strain during the cyclic loading. The functional compatibility of a
      biodegradable synthetic graft and, therefore, the global mechanical properties of
      the scaffold during degradation, can be optimised using computer-aiding and
      numerical tools. Therefore, in this work, the ability of numerical tools to
      predict the mechanical behaviour of the device during its degradation is
      discussed. Computational approaches based on elastoplastic and viscoplastic
      constitutive models are also presented. These models enable to simulate the
      plastic strain accumulation. These computational approaches, where the material
      model parameters depend on the hydrolytic degradation damage, are calibrated
      using experimental data measured from biodegradable suture fibres at different
      degradation steps. Due to durability requirements the selected materials are
      polydioxone (PDO) and polylactic acid and poly-caprolactone blend (PLA-PCL).
      Computational approaches investigated are able to predict well the experimental
      results for both materials, in full strain range until rupture and for different
      degradation steps. These approaches can be further used in more complex fibrous
      structures, to predict its global mechanical behaviour during degradation
      process. 

PMID- 26303169
TI  - Influence of virtual intervention and blood rheology on mass transfer through
      thoracic aortic aneurysm.
AB  - Computational fluid dynamics tools have been used to investigate blood flow
      through the human thoracic aortic models with aneurysm before and after virtual
      stent graft operation. The impact of blood rheology and aortic geometry on the
      wall shear stress (WSS), luminal surface low-density lipoproteins (LDL)
      concentration, and oxygen flux along the arterial wall is investigated. The stent
      graft at the aneurysm has significant effects on WSS and mass transport in blood
      flow. Due to the low flow rate, Newtonian blood assumption generally under
      estimates the WSS. The non-Newtonian blood rheology play an important role in the
      LDL transport as well as oxygen transport. It is found that WSS alone is
      insufficient to correctly predict the location with high risk of atherogenesis.
      The results suggest that WSS, luminal surface LDL concentration, and the oxygen
      flux on the wall have to be considered together to evaluate the performance of
      virtual operation. 

PMID- 26303170
TI  - Impact of Coronary Artery Anatomy in Arterial Switch Procedure on Early Mortality
      and Morbidity.
AB  - OBJECTIVE: Arterial switch operation has become the treatment of choice for
      neonates with transposition of the great arteries. The most important step of the
      procedure is transferring the coronary arteries to the neoaorta successfully.
      This study shows the impact of coronary anatomy on early mortality and morbidity
      after arterial switch operation. METHODS: Ninety-two patients with transposition
      of the great arteries who underwent arterial switch operation between October
      2010 and September 2014 were included in this retrospective study. The patients
      were classified into two groups: group I (n = 68, patients with usual coronary
      artery anatomy) and group II (n = 24, patients with unusual coronary artery
      anatomy). Median age was 10 days (6-25 days) in group I and 14 days (7-29 days)
      in group II. In group I, 25 patients had ventricular septal defect, nine patients
      had coarctation of the aorta or distal aortic arch hypoplasia, seven patients had
      Taussig Bing anomaly. In group II, nine patients had ventricular septal defect,
      one patient had coarctation of aorta, and one patient had Taussig Bing anomaly.
      RESULTS: Regarding the postoperative variables, no significant statistical
      difference was found between two groups. But cardiopulmonary bypass time is
      significantly longer in group II (P = .004). There was no difference in
      complications including the mortality (P = .265). It is statistically found that
      associated anomalies did not affect the mortality and complication rates. All
      mortality cases (n = 4) were related to ventricular dysfunction in group II,
      whereas only four of the eight patients died because of ventricular dysfunction
      in group I. CONCLUSION: Coronary artery pattern was not a predictor of mortality
      in early postoperative period. There may be an impact of unusual coronary artery
      pattern on the development of ventricular dysfunction as a cause of mortality.

PMID- 26303171
TI  - Design and synthesis of pyrazole/isoxazole linked arylcinnamides as tubulin
      polymerization inhibitors and potential antiproliferative agents.
AB  - As pyrazole and isoxazole based derivatives are well-known for displaying a
      considerable biological profile, an attempt has been made to unravel their
      cytotoxic potential. In this context, a number of pyrazole/isoxazole linked
      arylcinnamide conjugates (15a-o and 21a-n) have been synthesized by employing a
      straight forward route. The basic structure comprised three ring scaffolds (A, B
      and C): methoxyphenyl rings as A and C rings and a five membered heterocyclic
      ring (pyrazole or isoxazole) as the B-ring. To achieve clear understanding, these
      derivatives are categorized as pyrazole-phenylcinnamides (PP) and isoxazole
      phenylcinnamides (IP). These compounds have been evaluated for their ability to
      inhibit the growth of various human cancer cell lines such as HeLa, DU-145, A549
      and MDA-MB231 and most of them exhibit considerable cytotoxic effects. Some of
      them like 15a, 15b, 15e, 15i and 15l exhibit promising cytotoxicity in HeLa cells
      (IC50 = 0.4, 1.8, 1.2, 2.7 and 1.7 MUM). Amongst them 15a, 15b and 15e were taken
      up for detailed biological studies, they were found to arrest the cells in the
      G2/M phase of the cell cycle. Moreover, they were investigated for their effect
      on the microtubular cytoskeletal system by using a tubulin polymerization assay,
      immunofluroscence and molecular docking studies; interestingly they demonstrate a
      significant inhibition of tubulin polymerization. 

PMID- 26303172
TI  - [Management of arterial hypertension].
AB  - Arterial hypertension is one of the most frequent diseases in the western world
      and is one of the three most important risk factors for heart diseases. The 2013
      guidelines of the European Societies of Hypertension and Cardiology (ESH/ESC)
      provide a clear action plan for evidence-based diagnostics and therapeutic
      measures in hypertensive subjects and simplify target blood pressures across
      various patient groups. Non-pharmacological options play a central role in the
      treatment of arterial hypertension. The indications for drug therapy arise from
      three criteria including the level of hypertension, risk profile of the patient,
      as well as response to non-pharmacological therapy. For the first choice
      monotherapy five substance groups are available: diuretics, beta blockers,
      angiotensin-converting enzyme (ACE) inhibitors, angiotensin (AT) 1 receptor
      antagonists and calcium antagonists. By combination therapy, the responder rate
      can be significantly increased with respect to a normalization of blood pressure.
      A true treatment resistance, in which the therapeutic goal is not reached in
      spite of a triple combination with maximum dosage, is extremely rare. Further
      treatment options are combinations of four drug classes and changes of
      medication. Hypertensive emergencies require a rapid intervention; nevertheless,
      the magnitude of blood pressure lowering can greatly vary depending on the
      individual clinical picture. 

PMID- 26303173
TI  - More Than Just Light: Clinical Relevance of Light Perception in the Nosocomial
      Pathogen Acinetobacter baumannii and Other Members of the Genus Acinetobacter.
AB  - A summary of the major findings concerning light modulation in Acinetobacter
      baumannii, which governs aspects related to the success of this microorganism as
      a nosocomial pathogen, is presented. Particularly, the evidence shows that light
      modulates the ability of the bacteria to persist in the environment, its
      virulence against eukaryotic hosts and even susceptibility to certain
      antibiotics. The light signal is sensed through different mechanisms, in some
      cases involving specialized photoreceptors of the BLUF-type, whereas in others,
      directly by a photosensitizer molecule. We also provide new data concerning the
      genomic context of BLUF-domain containing proteins within the genus
      Acinetobacter, as well as further insights into the mechanism of light-mediated
      reduction in susceptibility to antibiotics. The overall information points toward
      light being a crucial stimulus in the lifestyle of members of the genus
      Acinetobacter as well as in other clinically relevant species, such as members of
      the ESKAPE group, playing therefore an important role in the clinical settings. 

PMID- 26303174
TI  - Exosomes: A Promising Factor Involved in Cancer Hypoxic Microenvironments.
AB  - As a significant tumor feature, hypoxia can trigger cancer adaptive processes,
      induce malignant phenotype development, and promote drug resistance. Previous
      studies demonstrated that exosomes are critical during these procedures. Exosomes
      are small vesicles formed in vesicular bodies in the endosomal network. These
      small vesicles are mainly involved in the transport of bioactive molecules
      between cells. Exosomes are also involved in the mediation of some cellular
      communications depending on derived donor cells; thus, recipient cells undergo
      phenotypic changes. Furthermore, hypoxia can remarkably stimulate exosomal
      secretion; for instance, nucleic acids and proteins as transmission signals in
      exosomes in a tumor microenvironment are involved in various functions, such as
      inducing intratumoral heterogeneity, altering immunological responses, producing
      cancer-associated fibroblasts, and promoting angiogenesis and metastasis.
      Moreover, exosome contents resemble those of a donor cell; this finding indicates
      that exosomes may also be regarded as suitable biomarkers of hypoxia status.
      Therefore, exosomes can be used to facilitate diagnosis and prognosis with
      minimal invasive procedures. Further studies on exosomes in cancer may provide
      new therapeutic strategies. 

PMID- 26303175
TI  - Rational Development of Nucleoside Diphosphate Prodrugs: DiPPro-Compounds.
AB  - The bio-reversible protection of nucleoside diphosphates is summarized. The
      design, hydrolytic characteristics, and the antiviral activity of these prodrugs
      of NDPs are described. In contrast to earlier attempts, the DiPPro-approach [beta
      (bis(acyloxybenzyl) nucleoside diphosphates)] leads to the successful delivery of
      the desired nucleoside diphosphates. The stability towards hydrolysis is
      dependent on the specific acyl moieties in the bis(acyloxybenzyl) unit as well as
      on the particular nucleoside analogue. Hydrolysis studies in aqueous PBS buffer
      (pH 7.3), 20 % human plasma in PBS, RPMI-1640 culture medium, and CEM cell
      extracts were carried out. Contrary to a high chemical and plasma stability, the
      compounds showed a very low half-life in CEM cell extracts, and efficiently
      released the nucleoside analogues diphosphates, e.g. of AZT, d4T and BVDU. Two
      additional types of cycloSal- NDP prodrugs were studied but neither proved to be
      useful as nucleoside diphosphate prodrugs. In summary, the results led to the
      development of a new series of non-symmetric nucleoside diphosphate prodrugs that
      selectively delivered the nucleoside diphosphate in cell extracts. 

PMID- 26303176
TI  - Endosome Escape Strategies for Improving the Efficacy of Oligonucleotide Delivery
      Systems.
AB  - Gene therapy requires safe and effective vectors to deliver genes to their target
      site of action. Non-viral gene delivery systems have attracted growing attention
      due to their low toxicity, low immunogenicity and ease of production compared to
      viral vectors. Most non-viral gene delivery systems enter cells via endocytic
      pathways, and their escape from endosomes is therefore crucial for successful
      transfection. Several reagents have been developed to promote endosomal escape,
      including peptides, polymers and lipids. Among these, endosome-disrupting
      peptides have been used in many studies, and have proven to be one of the most
      promising approaches to overcome endosomal entrapment and lysosomal degradation.
      This review provides an up-to-date summary of strategies for enhancing endosomal
      escape, with a focus on the modification of endosome-disrupting peptides to
      further increase the efficient delivery of oligonucleotides. 

PMID- 26303177
TI  - Intervertebral disc "dysgeneration".

PMID- 26303179
TI  - Promoting multidisciplinary collaboration: letter to the editor in response to
      Schoenfeld AJ, Bhalla A, George J, Harris MB, Bono CM, "Academic productivity and
      contributions to the literature among spine surgery fellowship faculty".

PMID- 26303180
TI  - Measuring academic productivity in spine surgery: in reply.

PMID- 26303178
TI  - Novel diagnostic and prognostic methods for disc degeneration and low back pain.

PMID- 26303181
TI  - Letter concerning "hidden blood loss during posterior spine fusion surgery" by
      Yossi et al.

PMID- 26303182
TI  - Hidden blood loss during posterior spine fusion surgery: in response to the
      letter by ZhiNan et al.

PMID- 26303185
TI  - Simple Surfactant Concentration-Dependent Shape Control of Polyhedral Fe3 O4
      Nanoparticles and Their Magnetic Properties.
AB  - The shape and size of monodisperse Fe3 O4 nanoparticles (NPs) are controlled
      using a chemical solution synthesis in the presence of the surfactant
      cetylpyridinium chloride (CPC). Cubic Fe3 O4 NPs surrounded by six {100} planes
      are obtained in the absence of CPC. Increasing the CPC content during synthesis
      causes the shape of the resulting Fe3 O4 NPs to change from cubic to truncated
      cubic, cuboctahedral, truncated octahedral, and finally octahedral. During this
      evolution, the predominantly exposed planes of the Fe3 O4 NPs vary from {100} to
      {111}. The shape control results from the synergistic effect of the pyridinium
      cations, chloride anions, and long-chain alkyl groups of CPC, which is confirmed
      by comparison with NPs synthesized in the presence of various related cationic
      surfactants. The size of the cubic Fe3 O4 NPs can be tuned from 50 to 200 nm, by
      changing the concentration of oleic acid in the reaction solution. The Fe3 O4 NPs
      exhibit shape-dependent saturation magnetization, remanent magnetization, and
      coercivity. 

PMID- 26303184
TI  - Cigarette smoking leads to persistent and dose-dependent alterations of brain
      activity and connectivity in anterior insula and anterior cingulate.
AB  - Although many smokers try to quit smoking, only about 20-25 percent will achieve
      abstinence despite 6 months or more of gold-standard treatment. This low success
      rate suggests long-term changes in the brain related to smoking, which remain
      poorly understood. We compared ex-smokers to both active smokers and non-smokers
      using functional magnetic resonance imaging (fMRI) to explore persistent
      modifications in brain activity and network organization. This prospective and
      consecutive study includes 18 non-smokers (29.5 +/- 6.7 years of age, 11 women),
      14 smokers (>=10 cigarettes a day >2 years of smoking, 29.3 +/- 6.0 years of age,
      10 women) and 14 ex-smokers (>1 year of quitting 30.5 +/- 5.7 years of age, 10
      women). Participants underwent a block-design fMRI study contrasting smoking cue
      with control (neutral cue) videos. Data analyses included task-related general
      linear model, seed-based functional connectivity, voxel-based morphometry (VBM)
      of gray matter and tract-based spatial statistics (TBSS) of white matter. Smoking
      cue videos versus control videos activated the right anterior insula in ex
      smokers compared with smokers, an effect correlating with cumulative nicotine
      intake (pack-years). Moreover, ex-smokers had a persistent decrease in functional
      connectivity between right anterior insula and anterior cingulate cortex (ACC)
      compared with control participants, but similar to active smokers. Potentially
      confounding alterations in gray or white matter were excluded in VBM and TBSS
      analyses. In summary, ex-smokers with long-term nicotine abstinence have
      persistent and dose-dependent brain network changes notably in the right anterior
      insula and its connection to the ACC. 

PMID- 26303183
TI  - A Mouse Model of Targeted Musashi1 Expression in Whole Intestinal Epithelium
      Suggests Regulatory Roles in Cell Cycle and Stemness.
AB  - The intestinal epithelium is very peculiar for its continuous cell renewal,
      fuelled by multipotent stem cells localized within the crypts of Lieberkuhn.
      Several lines of evidence have established the evolutionary conserved RNA-binding
      protein Musashi1 as a marker of adult stem cells, including those of the
      intestinal epithelium, and revealed its roles in stem cell self-renewal and cell
      fate determination. Previous studies from our laboratories have shown that
      Musashi1 controls stem cell-like features in medulloblastoma, glioblastoma, and
      breast cancer cells, and has pro-proliferative and pro-tumorigenic properties in
      intestinal epithelial progenitor cells in vitro. To undertake a detailed study of
      Musashi1's function in the intestinal epithelium in vivo, we have generated a
      mouse model, referred to as v-Msi, overexpressing Musashi1 specifically in the
      entire intestinal epithelium. Compared with wild type litters, v-Msi1 mice
      exhibited increased intestinal crypt size accompanied by enhanced proliferation.
      Comparative transcriptomics by RNA-seq revealed Musashi1's association with gut
      stem cell signature, cell cycle, DNA replication, and drug metabolism. Finally,
      we identified and validated three novel mRNA targets that are stabilized by
      Musashi1, Ccnd1 (Cyclin D1), Cdk6, and Sox4. In conclusion, the targeted
      expression of Musashi1 in the intestinal epithelium in vivo increases the cell
      proliferation rate and strongly suggests its action on stem cells activity. This
      is due to the modulation of a complex network of gene functions and pathways
      including drug metabolism, cell cycle, and DNA synthesis and repair.

PMID- 26303186
TI  - Benefit of Early Palliative Care Intervention in End-Stage Liver Disease Patients
      Awaiting Liver Transplantation.
AB  - BACKGROUND: Patients with end-stage liver disease have a predictable and
      progressive decline in their quality of life because of physical symptoms and
      psychological distress. Early palliative care intervention (EPCI) correlates with
      better symptom control and mood. We aimed to improve symptomatology and mood in
      liver transplant candidates by implementing a longitudinal multidisciplinary
      EPCI. MEASURES: Depression level and symptom burden were assessed with Center for
      Epidemiological Studies Depression Scale and a modified liver-specific Edmonton
      Symptom Assessment System scale. INTERVENTION: All patients referred for liver
      transplant evaluation between July 2013 and May 2014 were scheduled for EPCI.
      OUTCOMES: After EPCI, 50% of moderate-to-severe symptoms improved (P < 0.05), and
      43% of patients showed improvement in clinically significant depressive symptoms
      (P = 0.003). Notably, patients with more symptoms showed a greater improvement in
      Center for Epidemiological Studies Depression Scale scores (P = 0.001).
      CONCLUSIONS/LESSONS LEARNED: Implementation of EPCI improved symptom burden and
      mood in end-stage liver disease patients awaiting transplant.

PMID- 26303187
TI  - Complex Decongestive Lymphatic Therapy With or Without Vodder II Manual Lymph
      Drainage in More Severe Chronic Postmastectomy Upper Limb Lymphedema: A
      Randomized Noninferiority Prospective Study.
AB  - CONTEXT: Complex decongestive lymphatic therapy (CDT) has been the method of
      choice in conservative management of lymphedema. Although effective, it is time
      consuming and manual lymph drainage (MLD) usually requires skilled therapists.
      OBJECTIVES: The purpose of this study was to compare the reduction in edema
      volume in more advanced (>=20% limb volume difference) postmastectomy arm
      lymphedema achieved by compression bandaging (CB) and physical exercises vs. the
      same management augmented by an additional 30 minutes of MLD (Vodder II method).
      METHODS: Sixty postmastectomy women were randomly assigned to either the CB group
      or the CDT group. Of those, 51 women (26 within the CB group) completed 26 weeks
      of therapy (two weeks of the intensive phase and six months of the maintenance
      phase). RESULTS: A decrease of limb volume (15.6% in the CB group and 13.8% in
      the CDT group), edema volume (47.2% and 47.4%, respectively), and limb-related
      volume change (14.7% and 12.5%) during the intensive phase were observed. This
      improvement remained constant in both groups after six months of maintenance
      therapy. The health-related quality of life (measured by the Lymphedema
      Questionnaire) similarly showed improvement in both groups, with a high level of
      treatment satisfaction. CONCLUSION: These results indicate that parallel
      (immediate and delayed) results may be obtained by CDT without the use of Vodder
      MLD and CB may be an essential part of lymphedema management.

PMID- 26303188
TI  - Fentanyl Buccal Tablet vs. Oral Morphine in Doses Proportional to the Basal
      Opioid Regimen for the Management of Breakthrough Cancer Pain: A Randomized,
      Crossover, Comparison Study.
AB  - CONTEXT: Fentanyl products have shown superiority to oral opioids for the
      management of breakthrough cancer pain (BTcP). However, these studies did not use
      appropriate patient selection, and drugs have been compared by using different
      rationales. OBJECTIVES: The aim of this randomized, crossover, controlled study
      was to compare efficacy and safety of fentanyl buccal tablets (FBTs) and oral
      morphine (OM), given in doses proportional to opioid daily doses. METHODS: Cancer
      patients with pain receiving >=60 mg or more of oral morphine equivalents per day
      and presenting with <=3 episodes of BTcP per day were included. In a randomized,
      crossover manner, patients received FBT or OM at doses proportional to the daily
      opioid regimen in four consecutive episodes of BTcP. Pain intensity was measured
      before (T0) and 15 (T15) and 30 minutes (T30), after study drugs. RESULTS: In
      total, 263 episodes of BTcP were treated. A statistical difference in changes in
      pain intensity-decrease of >=33% and >=50%-between the two groups was observed at
      T15 and T30 (P < 0.0005). No severe adverse effects after study drug
      administration were observed. CONCLUSION: When used in doses proportional to the
      basal opioid regimen, FBT showed a clear superiority and was well tolerated when
      compared with OM during the first 30 minutes, which is the approximate target for
      a timely intervention required for a BTcP medication.

PMID- 26303189
TI  - Report on the effects of fragment size, indexing, and read length on HLA
      sequencing on the Illumina MiSeq.
AB  - Single-molecule sequencing should allow for unambiguous, accurate, and high
      throughput HLA typing. In this proof of principle study, we investigated the
      effects of fragment size for library preparation, indexing strategy, and read
      length on HLA typing. Whole gene amplicons of HLA-A, B, C, DRB1, and DQB1 were
      obtained by long-range PCR. For library preparation, two fragment sizes were
      evaluated: 100-300bp and 300-600bp. For sample multiplexing, two indexing
      strategies were compared: indexing-by-amplicon, where each individual amplicon is
      barcoded, and indexing-by-patient, where each patient's five loci are equimolarly
      pooled after PCR and indexed with the same barcode. Sequencing was performed on
      an Illumina MiSeq instrument using paired-end 150bp and 250bp read lengths. Our
      results revealed that the 300-600bp fragments in the 2*250 MiSeq group gave the
      most accurate sequencing results. There was no difference in HLA typing results
      between the two indexing strategies, suggesting that indexing-by-patient, which
      is much simpler, is a viable option. In conclusion, enzymatic fragmentation of
      pooled whole gene amplicons is a suitable strategy for HLA typing by next
      generation sequencing on the Illumina MiSeq. 

PMID- 26303190
TI  - Characterization of a new transmission detector for patient individualized online
      plan verification and its influence on 6MV X-ray beam characteristics.
AB  - PURPOSE: Online verification and 3D dose reconstruction on daily patient anatomy
      have the potential to improve treatment delivery, accuracy and safety. One
      possible implementation is to recalculate dose based on online fluence
      measurements with a transmission detector (TD) attached to the linac. This study
      provides a detailed analysis of the influence of a new TD on treatment beam
      characteristics. METHODS: The influence of the new TD on surface dose was
      evaluated by measurements with an Advanced Markus Chamber (Adv-MC) in the build
      up region. Based on Monte Carlo simulations, correction factors were determined
      to scale down the over-response of the Adv-MC close to the surface. To analyze
      the effects beyond dmax percentage depth dose (PDD), lateral profiles and
      transmission measurements were performed. All measurements were carried out for
      various field sizes and different SSDs. Additionally, 5 IMRT-plans (head & neck,
      prostate, thorax) and 2 manually created test cases (3*3cm(2) fields with
      different dose levels, sweeping gap) were measured to investigate the influence
      of the TD on clinical treatment plans. To investigate the performance of the TD,
      dose linearity as well as dose rate dependency measurements were performed.
      RESULTS: With the TD inside the beam an increase in surface dose was observed
      depending on SSD and field size (maximum of +11%, SSD = 80cm, field size =
      30*30cm(2)). Beyond dmax the influence of the TD on PDDs was below 1%. The
      measurements showed that the transmission factor depends slightly on the field
      size (0.893-0.921 for 5*5cm(2) to 30*30cm(2)). However, the evaluation of
      clinical IMRT-plans measured with and without the TD showed good agreement after
      using a single transmission factor (gamma(2%/2mm) > 97%, delta+/-3% >95%).
      Furthermore, the response of TD was found to be linear and dose rate independent
      (maximum difference <0.5% compared to reference measurements). CONCLUSIONS: When
      placed in the path of the beam, the TD introduced a slight, clinically acceptable
      increase of the skin dose even for larger field sizes and smaller SSDs and the
      influence of the detector on the dose beyond dmax as well as on clinical IMRT
      plans was negligible. Since there was no dose rate dependency and the response
      was linear, the device is therefore suitable for clinical use. Only its
      absorption has to be compensated during treatment planning, either by the use of
      a single transmission factor or by including the TD in the incident beam model.

PMID- 26303191
TI  - Infracommunity dynamics of chiggers (Trombiculidae) parasitic on a rodent.
AB  - We studied the structure of chigger mite (Trombiculidae) communities parasitic on
      a South African rodent, Rhabdomys pumilio. We aimed to determine whether: (a)
      different chigger species differ in preferences for certain body areas of a host
      and (b) chigger assemblages among body areas of the same host individual, are
      structured and if so, whether the structure of these assemblages is aggregative
      or segregative. Rhabdomys pumilio is parasitized by seven chigger species
      belonging to six genera. The three most abundant species (Leptotrombidium sp. nr.
      muridium, Schoutedenichia sp. and Neoschoengastia sp. A) displayed a non-random
      distribution across the host body, with the two most abundant species (L. sp. nr.
      muridium and Schoutedenichia sp.) significantly associated with the tail area. In
      addition, whenever non-randomness of chigger co-occurrence in the same body area
      was recorded, it indicated positive but not negative co-occurrences of different
      species. This might be due to similarity of chigger species in resource needs and
      strategies to avoid host defence efforts. 

PMID- 26303192
TI  - The calcium-sensing receptor as a mediator of inflammation.
AB  - The teleologic link between increased production of pro-inflammatory cytokines
      resulting from a systemic inflammatory response to a burn injury and consequent
      stimulation of bone resorption is unclear. While it is known that cytokines can
      stimulate osteocytic and osteoblastic production of the ligand of the receptor
      activator of NFkappaB, or RANKL, it is not certain why this occurs. It was
      therefore hypothesized that the subsequent osteoclastic bone resorption liberates
      calcium from the bone matrix and somehow affects the inflammatory response. In
      this paper we show how the cytokine-mediated inflammatory response following
      severe burn injury in children results in simultaneous increase in bone
      resorption and up-regulation of the parathyroid calcium-sensing receptor. The
      acute bone resorption leads to release of calcium from the bone matrix with
      consequent calcium accumulation in the circulation. The up-regulation of the
      parathyroid calcium-sensing receptor suppresses the release of parathyroid
      hormone resulting in a lowering of blood calcium concentration. The simultaneous
      occurrences of these processes could regulate blood calcium concentration and if
      calcium concentration affects the inflammatory response, then the calcium-sensing
      receptor could, at the very least, modulate the inflammatory response by
      adjusting the blood calcium concentration. We describe in vitro studies in which
      we demonstrated that peripheral blood mononuclear cells in culture produce the
      chemokines MIP-1alpha and RANTES in proportion to the medium calcium
      concentration and they produce the chemokine MCP-1 in quantities inversely
      related to medium calcium concentration. CD14+monocytes in culture will also
      produce MIP-1alpha in direct relationship to medium calcium concentration but the
      correlation coefficient is markedly reduced compared to that with peripheral
      blood mononuclear cells. These monocytes, which possess the calcium-sensing
      receptor, do not produce MCP-1 in either direct or inverse relationship to medium
      calcium concentration. Therefore, it is possible that other peripheral blood
      mononuclear cells are primarily responsible for the production of chemokines in
      relation to calcium concentration but these cells have not yet been defined. 

PMID- 26303193
TI  - Phenotype and Genotype in a Cohort of 312 Adult Patients with Nontransfusion
      Dependent Thalassemia in Northeast Thailand.
AB  - Patients with nontransfusion-dependent thalassemia (NTDT) do not require regular
      blood transfusion for survival but may encounter several complications that
      contribute to morbidity and mortality. We report the molecular heterogeneity and
      hematological features of NTDT in 312 adult patients in northeast Thailand.
      Hemoglobin (Hb) and DNA analyses identified 177 subjects with Hb E-beta
      thalassemia, 1 with homozygous beta0-thalassemia and 134 with Hb H, AEBart's and
      EEBart's diseases. For beta-thalassemia, 12 different mutations including both
      beta0- and beta+-thalassemias were detected. Coinheritance of alpha-thalassemia
      as an ameliorating factor was observed in 18 of 178 cases (10.1%) with beta
      thalassemia. The alpha-globin gene triplicated haplotype (alphaalphaalphaanti3.7)
      was observed in 1 case of Hb E-beta0-thalassemia. The presence of the -158
      (Cx2192;T) Gx03B3;-XmnI polymorphism (+/+) was found to be associated with
      increased Hb F expression, but its frequency in the studied subjects was low.
      Those with alpha-thalassemia included 17 with deletional and 51 nondeletional Hb
      H, and 63 with AEBart's and 3 with EEBart's diseases. The hematological
      parameters of these NTDT and genotype-phenotype relationships are presented. The
      diverse molecular heterogeneity of NTDT underlines the importance of complete
      genotyping of the patient. These results should prove useful for management
      planning, the prediction of clinical outcome and to improve genetic counseling
      for NTDT patients. 

PMID- 26303196
TI  - The Association of HIV-Related Stigma to HIV Medication Adherence: A Systematic
      Review and Synthesis of the Literature.
AB  - This paper provides a review of the quantitative literature on HIV-related stigma
      and medication adherence, including: (1) synthesis of the empirical evidence
      linking stigma to adherence, (2) examination of proposed causal mechanisms of the
      stigma and adherence relationship, and (3) methodological critique and guidance
      for future research. We reviewed 38 studies reporting either cross-sectional or
      prospective analyses of the association of HIV-related stigma to medication
      adherence since the introduction of antiretroviral therapies (ART). Although
      there is substantial empirical evidence linking stigma to adherence difficulties,
      few studies provided data on psychosocial mechanisms that may account for this
      relationship. Proposed mechanisms include: (a) enhanced vulnerability to mental
      health difficulties, (b) reduction in self-efficacy, and (c) concerns about
      inadvertent disclosure of HIV status. Future research should strive to assess the
      multiple domains of stigma, use standardized measures of adherence, and include
      prospective analyses to test mediating variables. 

PMID- 26303195
TI  - Influence of dietary fat and carbohydrates proportions on plasma lipids, glucose
      control and low-grade inflammation in patients with type 2 diabetes-The TOSCA.IT
      Study.
AB  - PURPOSE: The optimal macronutrient composition of the diet for the management of
      type 2 diabetes is debated, particularly with regard to the ideal proportion of
      fat and carbohydrates. The aim of the study was to explore the association of
      different proportions of fat and carbohydrates of the diet-within the ranges
      recommended by different guidelines-with metabolic risk factors. METHODS: We
      studied 1785 people with type 2 diabetes, aged 50-75, enrolled in the TOSCA.IT
      Study. Dietary habits were assessed using a validated food-frequency
      questionnaire (EPIC). Anthropometry, fasting lipids, HbA1c and C-reactive protein
      (CRP) were measured. RESULTS: Increasing fat intake from <25 to >=35 % is
      associated with a significant increase in LDL-cholesterol, triglycerides, HbA1c
      and CRP (p < 0.05). Increasing carbohydrates intake from <45 to >=60 % is
      associated with significantly lower triglycerides, HbA1c and CRP (p < 0.05). A
      fiber intake >=15 g/1000 kcal is associated with a better plasma lipids profile
      and lower HbA1c and CRP than lower fiber consumption. A consumption of added
      sugars of >=10 % of the energy intake is associated with a more adverse plasma
      lipids profile and higher CRP than lower intake. CONCLUSIONS: In people with type
      2 diabetes, variations in the proportion of fat and carbohydrates of the diet,
      within the relatively narrow ranges recommended by different nutritional
      guidelines, significantly impact on the metabolic profile and markers of low
      grade inflammation. The data support the potential for reducing the intake of fat
      and added sugars, preferring complex, slowly absorbable, carbohydrates.

PMID- 26303194
TI  - Main nutrient patterns are associated with prospective weight change in adults
      from 10 European countries.
AB  - PURPOSE: Various food patterns have been associated with weight change in adults,
      but it is unknown which combinations of nutrients may account for such
      observations. We investigated associations between main nutrient patterns and
      prospective weight change in adults. METHODS: This study includes 235,880
      participants, 25-70 years old, recruited between 1992 and 2000 in 10 European
      countries. Intakes of 23 nutrients were estimated from country-specific validated
      dietary questionnaires using the harmonized EPIC Nutrient DataBase. Four nutrient
      patterns, explaining 67 % of the total variance of nutrient intakes, were
      previously identified from principal component analysis. Body weight was measured
      at recruitment and self-reported 5 years later. The relationship between nutrient
      patterns and annual weight change was examined separately for men and women using
      linear mixed models with random effect according to center controlling for
      confounders. RESULTS: Mean weight gain was 460 g/year (SD 950) and 420 g/year (SD
      940) for men and women, respectively. The annual differences in weight gain per
      one SD increase in the pattern scores were as follows: principal component (PC)
      1, characterized by nutrients from plant food sources, was inversely associated
      with weight gain in men (-22 g/year; 95 % CI -33 to -10) and women (-18 g/year;
      95 % CI -26 to -11). In contrast, PC4, characterized by protein, vitamin B2,
      phosphorus, and calcium, was associated with a weight gain of +41 g/year (95 % CI
      +2 to +80) and +88 g/year (95 % CI +36 to +140) in men and women, respectively.
      Associations with PC2, a pattern driven by many micro-nutrients, and with PC3, a
      pattern driven by vitamin D, were less consistent and/or non-significant.
      CONCLUSIONS: We identified two main nutrient patterns that are associated with
      moderate but significant long-term differences in weight gain in adults.

PMID- 26303197
TI  - The use of mystery shopping for quality assurance evaluations of HIV/STI testing
      sites offering services to young gay and bisexual men.
AB  - Young men who have sex with men (YMSM) are at increased risk for HIV and STI
      infection. While encouraging HIV and STI testing among YMSM remains a public
      health priority, we know little about the cultural competency of providers
      offering HIV/STI tests to YMSM in public clinics. As part of a larger
      intervention study, we employed a mystery shopper methodology to evaluate the
      LGBT cultural competency and quality of services offered in HIV and STI testing
      sites in Southeast Michigan (n = 43).We trained and deployed mystery shoppers (n
      = 5) to evaluate the HIV and STI testing sites by undergoing routine HIV/STI
      testing. Two shoppers visited each site, recording their experiences using a
      checklist that assessed 13 domains, including the clinic's structural
      characteristics and interactions with testing providers. We used the site scores
      to examine the checklist's psychometric properties and tested whether site
      evaluations differed between sites only offering HIV testing (n = 14) versus
      those offering comprehensive HIV/STI testing (n = 29). On average, site scores
      were positive across domains. In bivariate comparisons by type of testing site,
      HIV testing sites were more likely than comprehensive HIV/STI testing clinics to
      ascertain experiences of intimate partner violence, offer action steps to achieve
      safer sex goals, and provide safer sex education. The developed checklist may be
      used as a quality assurance indicator to measure HIV/STI testing sites'
      performance when working with YMSM. Our findings also underscore the need to
      bolster providers' provision of safer sex education and behavioral counseling
      within comprehensive HIV/STI testing sites. 

PMID- 26303199
TI  - Enzyme-responsive pillar[5]arene-based polymer-substituted amphiphiles:
      synthesis, self-assembly in water, and application in controlled drug release.
AB  - An enzyme-responsive drug delivery system was constructed from a pillar[5]arene
      based polyethyleneglycol-substituted amphiphile which self-assembles into
      micelles in water. These micelles exhibit superior drug encapsulation capability,
      and display drug release behaviour in response to enzyme catalysis, in particular
      to L-asparaginase. Doxorubicin-loaded micelles show significant cytotoxicity
      against MCF-7 cancer cells.

PMID- 26303198
TI  - Learning-related representational changes reveal dissociable integration and
      separation signatures in the hippocampus and prefrontal cortex.
AB  - The episodic memory system enables accurate retrieval while maintaining
      flexibility by representing both specific episodes and generalizations across
      events. Although theories suggest that the hippocampus (HPC) is dedicated to
      represent specific episodes while the medial prefrontal cortex (MPFC)
      generalizes, other accounts posit that HPC can also integrate related memories.
      Here we use high-resolution functional magnetic resonance imaging in humans to
      examine how representations of memory elements change to either differentiate or
      generalize across related events. We show that while posterior HPC and anterior
      MPFC maintain distinct memories for individual events, anterior HPC and posterior
      MPFC integrate across memories. Integration is particularly likely for
      established memories versus those encoded simultaneously, highlighting the
      greater impact of prior knowledge on new encoding. We also show dissociable
      coding signatures in ventrolateral PFC, a region previously implicated in
      interference resolution. These data highlight how memory elements are represented
      to simultaneously promote generalization across memories and protect from
      interference. 

PMID- 26303200
TI  - Cytoophidium assembly reflects upregulation of IMPDH activity.
AB  - Cytidine triphosphate synthase (CTPS) and inosine monophosphate dehydrogenase
      (IMPDH) (both of which have two isoforms) can form fiber-like subcellular
      structures termed 'cytoophidia' under certain circumstances in mammalian cells.
      Although it has been shown that filamentation of CTPS downregulates its activity
      by disturbing conformational changes, the activity of IMPDH within cytoophidia is
      still unclear. Most previous IMPDH cytoophidium studies were performed under
      conditions involving inhibitors that impair GTP synthesis. Here, we show that
      IMPDH forms cytoophidia without inhibition of GTP synthesis. First, we find that
      an elevated intracellular CTP concentration or treatment with 3'-deazauridine, a
      CTPS inhibitor, promotes IMPDH cytoophidium formation and increases the
      intracellular GTP pool size. Moreover, restriction of cell growth triggers the
      disassembly of IMPDH cytoophidia, implying that their presence is correlated with
      active cell metabolism. Finally, we show that the presence of IMPDH cytoophidia
      in mouse pancreatic islet cells might correlate with nutrient uptake in the
      animal. Collectively, our findings reveal that formation of IMPDH cytoophidia
      reflects upregulation of purine nucleotide synthesis, suggesting that the IMPDH
      cytoophidium plays a role distinct from that of the CTPS cytoophidium in
      controlling intracellular nucleotide homeostasis. 

PMID- 26303201
TI  - Yeast Pmp3p has an important role in plasma membrane organization.
AB  - Pmp3p-related proteins are highly conserved proteins that exist in bacteria,
      yeast, nematodes and plants, and its transcript is regulated in response to
      abiotic stresses, such as low temperature or high salinity. Pmp3p was originally
      identified in Saccharomyces cerevisiae, and it belongs to the sensitive to Na(+)
      (SNA)-protein family, which comprises four members--Pmp3p/Sna1p, Sna2p, Sna3p and
      Sna4p. Deletion of the PMP3 gene conferred sensitivity to cytotoxic cations,
      whereas removal of the other SNA genes did not lead to clear phenotypic effects.
      It has long been believed that Pmp3p-related proteins have a common and important
      role in the modulation of plasma membrane potential and in the regulation of
      intracellular ion homeostasis. Here, we show that several growth phenotypes
      linked to PMP3 deletion can be modulated by the removal of specific genes
      involved in sphingolipid synthesis. These genetic interactions, together with
      lipid binding assays and epifluorescence microscopy, as well as other biochemical
      experiments, suggest that Pmp3p could be part of a phosphoinositide-regulated
      stress sensor.

PMID- 26303203
TI  - Incorporation of lanthanide (Eu(3+)) ions in ZnS semiconductor quantum dots with
      a trapped-dopant model and their photoluminescence spectroscopy study.
AB  - Doping quantum dots (QDs) with lanthanide (Ln) ions is promising to modify the
      optical properties of QDs, but incorporating Ln(3+) ions into QD hosts remains a
      challenge. In this work, we adopt the trapped-dopant model for fabricating Eu
      doped ZnS QDs via direct wet chemical synthesis. Sharp Eu dopant
      photoluminescence (PL) was observed in the PL spectra of the as-prepared Eu-doped
      ZnS QDs and the bands at ~590, ~618 and ~695 nm were assigned to transitions from
      (5)D0 to (7)F1, (7)F2 and (7)F4, respectively. Quenching of the ZnS bandgap PL
      and enhancement of the Eu dopant PL were observed with increasing Eu(3+) doping
      concentration, and also, the excitation spectra for Eu emission (618 nm) were
      similar to the typical excitonic features of the ZnS host. These spectroscopic
      results, as well as the XRD and EDS data, demonstrated that Eu(3+) ions were
      incorporated in the ZnS host rather than just on the surface, and the Eu dopant
      PL was derived from energy transfer from the QD host to Eu(3+) rather than direct
      excitation of Eu(3+). By surface passivation, the sharp Eu emission was well
      separated from the ZnS bandgap emission, which led to a good signal-to-noise
      ratio for more sensitive detection.

PMID- 26303202
TI  - Low levels of endogenous or X-ray-induced DNA double-strand breaks activate
      apoptosis in adult neural stem cells.
AB  - The embryonic neural stem cell compartment is characterised by rapid
      proliferation from embryonic day (E)11 to E16.5, high endogenous DNA double
      strand break (DSB) formation and sensitive activation of apoptosis. Here, we ask
      whether DSBs arise in the adult neural stem cell compartments, the sub
      ventricular zone (SVZ) of the lateral ventricles and the sub-granular zone (SGZ)
      of the hippocampal dentate gyrus, and whether they activate apoptosis. We used
      mice with a hypomorphic mutation in DNA ligase IV (Lig4(Y288C)), ataxia
      telangiectasia mutated (Atm(-/-)) and double mutant Atm(-/-)/Lig4(Y288C) mice. We
      demonstrate that, although DSBs do not arise at a high frequency in adult neural
      stem cells, the low numbers of DSBs that persist endogenously in Lig4(Y288C) mice
      or that are induced by low radiation doses can activate apoptosis. A temporal
      analysis shows that DSB levels in Lig4(Y288C) mice diminish gradually from the
      embryo to a steady state level in adult mice. The neonatal SVZ compartment of
      Lig4(Y288C) mice harbours diminished DSBs compared to its differentiated
      counterpart, suggesting a process selecting against unfit stem cells. Finally, we
      reveal high endogenous apoptosis in the developing SVZ of wild-type newborn mice.

PMID- 26303204
TI  - KPC2 relocalizes HOXA2 to the cytoplasm and decreases its transcriptional
      activity.
AB  - Regulation of transcription factor activity relies on molecular interactions or
      enzymatic modifications which influence their interaction with DNA cis-regulatory
      sequences, their transcriptional activation or repression, and stability or
      intracellular distribution of these proteins. Regarding the well-conserved Hox
      protein family, a restricted number of activity regulators have been highlighted
      thus far. In the framework of a proteome-wide screening aiming at identifying
      proteins interacting with Hoxa2, KPC2, an adapter protein constitutive of the KPC
      ubiquitin-ligase complex, was identified. In this work, KPC2 was confirmed as
      being a genuine interactor of Hoxa2 by co-precipitation and bimolecular
      fluorescence complementation assays. At functional level, KPC2 diminishes the
      transcriptional activity and induces the nuclear exit of Hoxa2. Gene expression
      analyses revealed that Kpc2 is active in restricted areas of the developing mouse
      embryo which overlap with the Hoxa2 expression domain. Together, our data support
      that KPC2 regulates Hoxa2 by promoting its relocation to the cytoplasm. 

PMID- 26303205
TI  - RISC assembly: Coordination between small RNAs and Argonaute proteins.
AB  - Non-coding RNAs generally form ribonucleoprotein (RNP) complexes with their
      partner proteins to exert their functions. Small RNAs, including microRNAs, small
      interfering RNAs, and PIWI-interacting RNAs, assemble with Argonaute (Ago) family
      proteins into the effector complex called RNA-induced silencing complex (RISC),
      which mediates sequence-specific target gene silencing. RISC assembly is not a
      simple binding between a small RNA and Ago; rather, it follows an ordered multi
      step pathway that requires specific accessory factors. Some steps of RISC
      assembly and RISC-mediated gene silencing are dependent on or facilitated by
      particular intracellular platforms, suggesting their spatial regulation. In this
      review, we summarize the currently known mechanisms for RISC assembly of each
      small RNA class and propose a revised model for the role of the chaperone
      machinery in the duplex-initiated RISC assembly pathway. This article is part of
      a Special Issue entitled: Clues to long noncoding RNA taxonomy1, edited by Dr.
      Tetsuro Hirose and Dr. Shinichi Nakagawa. 

PMID- 26303206
TI  - Hyperspectral interferometry: Sizing microscale surface features in the pine bark
      beetle.
AB  - A new method of interferometry employing a Fabry-Perot etalon model was used to
      locate and size microscale features on the surface of the pine bark beetle.
      Oscillations in the reflected light spectrum, caused by self-interference of
      light reflecting from surfaces of foreleg setae and spores on the elytrum, were
      recorded using white light hyperspectral microscopy. By making the assumption
      that pairs of reflecting surfaces produce an etalon effect, the distance between
      surfaces could be determined from the oscillation frequency. Low frequencies of
      less than 0.08 nm(-1) were observed in the spectrum below 700 nm while higher
      frequencies generally occupied wavelengths from 600 to 850 nm. In many cases, two
      frequencies appeared separately or in combination across the spectrum. The etalon
      model gave a mean spore size of 3.04 +/- 1.27 MUm and a seta diameter of 5.44 +/-
      2.88 MUm. The tapering near the setae tip was detected as a lowering of
      frequency. Spatial fringes were observed together with spectral oscillations from
      surfaces on the exoskeleton at higher magnification. These signals were
      consistent with embedded multi-layer reflecting surfaces. Possible applications
      for hyperspectral interferometry include medical imaging, detection of spore
      loads in insects and other fungal carriers, wafer surface and subsurface
      inspection, nanoscale materials, biological surface analysis, and spectroscopy
      calibration. This is, to our knowledge, the first report of oscillations directly
      observed by microscopy in the reflected light spectra from Coleoptera, and the
      first demonstration of broadband hyperspectral interferometry using microscopy
      that does not employ an internal interferometer.

PMID- 26303207
TI  - Principal findings of systematic reviews of acute asthma treatment in childhood.
AB  - OBJECTIVE: The objective of this study is to summarize the principal findings in
      the literature about acute asthma management in children. METHODS: Systematic
      reviews of randomized clinical trials (SRCTs) with or without meta-analysis in
      children (1-18 years) admitted to the emergency department (ED) were retrieved
      using five data bases. Methodological quality was determined using the AMSTAR
      tool. RESULTS: One hundred and three studies were retrieved. Among those, 28
      SRCTs were included: seven SRCTs related to short-acting beta2-agonists (SABA),
      three to ipratropium bromide (IB), eight to corticosteroids, one to racemic
      adrenaline, one to leukotriene receptor antagonists (LTRA), four to magnesium
      sulfate, one to intravenous (IV) SABA, one to IV aminophylline, one to IV
      ketamine, and one to antibiotics. It was determined that administering SABA by
      MDI-VHC is superior to using a nebulizer, because it decreases the hospital
      admission rate, improves the clinical score, results in a shorter time in the ED,
      and causes fewer adverse effects. Levalbuterol and albuterol were similar. In
      patients with moderate to severe exacerbations, IB+SABA was superior to SABA,
      decreasing hospital admission and improving the clinical score. SABA heliox
      administered by nebulizer decreased exacerbation severity compared to oxygen.
      Inhaled corticosteroids (ICS), especially administered by nebulizer, showed
      results similar to oral corticosteroids (OCS) with respect to reducing hospital
      admission, unscheduled visits, and the requirement of additional systemic
      corticosteroids. ICS or OCS following ED discharge was similar with regard to
      relapse. Compared with a placebo, IV magnesium reduced hospital admission and
      improved lung function. CONCLUSIONS: SRCTs are useful for guiding decisions in
      acute asthma treatment.

PMID- 26303208
TI  - The effect of citrate dialysate on intradialytic heparin dose in haemodialysis
      patients: study design of a randomised controlled trial.
AB  - BACKGROUND: Unfractionated heparin is the most common anticoagulant used in
      haemodialysis (HD), although it has many potential adverse effects. Citrate
      dialysate (CD) has an anticoagulant effect which may allow reduction in
      cumulative heparin dose (CHD) compared to standard acetate dialysate (AD).
      METHODS: This double-blinded, randomised, cross-over trial of chronic
      haemodialysis patients determines if CD allows reduction in CHD during HD
      compared with AD. After enrolment, intradialytic heparin is minimised during a
      two-week run-in period using a standardised protocol based on a visual clotting
      score. Patients still requiring intradialytic heparin after the run-in period are
      randomised to two weeks of HD with AD followed by two weeks of CD (Sequence 1) or
      two weeks of HD with CD followed by two weeks of AD (Sequence 2). The primary
      outcome is the change in CHD with CD compared with AD. Secondary outcomes include
      metabolic and haemodynamic parameters, and dialysis adequacy. DISCUSSION: This
      randomised controlled trial will determine the impact of CD compared with AD on
      CHD during HD. TRIAL REGISTRATION: ClinicalTrials.gov NCT01466959.

PMID- 26303209
TI  - How does batf3 determine dendritic cell development?

PMID- 26303211
TI  - Cyclin-Dependent Kinase 4/6 Inhibitors for the Treatment of Breast Cancer: A
      Review of Preclinical and Clinical Data.
AB  - For millions of women, breast cancer remains a potentially life-endangering
      diagnosis. With advances in research, new therapies targeted to tumor biology are
      emerging to treat the most common form of this disease. Cyclin-dependent kinase
      (CDK) 4/6 inhibitors are a new class of therapeutic agents that have the
      potential to improve the outcomes of patients with hormone receptor-positive
      (HR(+)) breast cancer. Three CDK 4/6 inhibitors have been investigated for the
      treatment of HR(+) breast cancer, including palbociclib (PD 0332991), ribociclib
      (LEE011), and abemaciclib (LY2835219). Palbociclib recently received accelerated
      Food and Drug Administration approval for the treatment of HR(+) metastatic
      breast cancer in combination with letrozole, and recent data suggest improved
      outcome when combined with fulvestrant. In this article, the mechanism of action
      of CDK 4/6 inhibitors, preclinical studies on their efficacy, ongoing clinical
      trials in breast cancer, and toxicity profiles are reviewed. 

PMID- 26303210
TI  - TLR3 drives IRF6-dependent IL-23p19 expression and p19/EBI3 heterodimer formation
      in keratinocytes.
AB  - Interferon regulatory factor (IRF) family members impart cell-type specificity to
      toll-like receptor (TLR) signalling, and we recently identified a role for IRF6
      in TLR2 signalling in epithelial cells. TLR3 has a well-characterized role in
      wound healing in the skin, and here, we examined TLR3-dependent IRF6 functions in
      human keratinocytes. Primary keratinocytes responded robustly to the TLR3 agonist
      poly(IC) with upregulation of mRNAs for interferon-beta (IFN-beta), the
      interleukin-12 (IL-12) family member IL-23p19 and the chemokines IL-8 and
      chemokine (C-C motif) ligand 5 (CCL5). Silencing of IRF6 expression enhanced
      poly(IC)-inducible IFN-beta mRNA levels and inhibited poly(IC)-inducible IL-23p19
      mRNA expression in primary keratinocytes. Consistent with these data, co
      transfection of IRF6 increased poly(IC)-inducible IL-23p19 promoter activity, but
      inhibited poly(IC)-inducible IFN-beta promoter activity in reporter assays.
      Surprisingly, poly(IC) did not regulate IL-12p40 expression in keratinocytes,
      suggesting that TLR3-inducible IL-23p19 may have an IL-23-independent function in
      these cells. The only other IL-12 family member that was strongly poly(IC)
      inducible was EBI3, which has not been shown to heterodimerize with IL-23p19.
      Both co-immunoprecipitation and proximity ligation assays revealed that IL-23p19
      and EBI3 interact in cells. Co-expression of IL-23p19 and EBI3, as compared with
      IL-23p19 alone, resulted in increased levels of secreted IL-23p19, implying a
      functional role for this heterodimer. In summary, we report that IRF6 regulates a
      subset of TLR3 responses in human keratinocytes, including the production of a
      novel IL-12 family heterodimer (p19/EBI3). We propose that the TLR3-IRF6-p19/EBI3
      axis may regulate keratinocyte and/or immune cell functions in the context of
      cell damage and wound healing in the skin. 

PMID- 26303212
TI  - Impact of Histone Deacetylase Inhibitors on microRNA Expression and Cancer
      Therapy: A Review.
AB  - Chromatin-modifying drugs, such as histone deacetylase inhibitors (HDACi), have
      shown potential as cancer therapeutics, either alone or in combination with other
      therapies. HDACi have the ability to reverse aberrant epigenetic modifications
      associated with cancer, namely dysregulated histone acetylation. There are
      currently three FDA approved HDACi; vorinostat, romidepsin, and panobinostat.
      Epigenetic modifications can regulate the expression of protein coding genes, and
      in addition can alter expression of microRNA (miRNA) genes. Many miRNAs play key
      roles in cell proliferation and apoptosis, and are commonly dysregulated in
      cancer states. A number of in vitro and in vivo studies have demonstrated the
      ability of chromatin-modifying drugs to alter miRNA expression, which may provide
      the basis for further investigation of miRNAs as therapeutic targets or as
      biomarkers of drug response. This review summarises findings from studies
      investigating the effects of HDACi on miRNA expression, as well as key clinical
      trials involving HDACi. Understanding how chromatin-modifying drugs
      epigenetically modulate miRNA genes provides further insight into the cellular
      mechanisms that deliver therapeutic responses, and may assist in refining
      treatment strategies.

PMID- 26303213
TI  - Emerging issues in invasive prenatal diagnosis: Safety and competency in the post
      NIPT era.
AB  - BACKGROUND: Numbers of invasive prenatal procedures are declining in response to
      improved aneuploidy screening methods. OBJECTIVE: To assess current practice and
      attitudes of clinicians performing invasive prenatal diagnosis in regard to
      patient consent and safety, maintaining procedural competence and uptake of
      chromosomal microarrays (CMAs). METHODS: Anonymous online survey of the
      Australian Association of Obstetrical and Gynaecological Ultrasonologists
      conducted in March 2015. RESULTS: The survey had a 45% response rate with 59
      respondents from Australia. Of these, 34 were subspecialists in maternal fetal
      medicine or obstetric and gynaecological ultrasound. Fifty-six (95%) currently
      performed amniocentesis or chorionic villus sampling. Of these, 14 (25%)
      performed <25 procedures and 8 (14%) performed >150 annually, with most
      respondents (60%) proposing 10-25 amniocenteses/year as adequate activity to
      maintain their skills. The majority neither expected referrers to provide results
      of hepatitis B and HIV serology, nor followed up missing results. There was
      uncertainty regarding the procedure-related vertical transmission risk of HBV in
      women with high viral load, with most respondents stating they were either unsure
      of the risk (22%) or that the risk was unknown (30%). Fifty per cent of
      practitioners routinely ordered CMA after invasive testing; all recommended CMA
      following a diagnosis of structural abnormality. CONCLUSIONS: In a period of
      declining testing, many Australian specialists are performing <25 procedures
      annually. Consideration of the potential risks of bloodborne viruses is limited.
      CMAs are rapidly being incorporated into clinical practice. These data have
      implications for patient consent and safety, and workforce training and practice.

PMID- 26303214
TI  - Reduced USP39 expression inhibits malignant proliferation of medullary thyroid
      carcinoma in vitro.
AB  - BACKGROUND: Medullary thyroid carcinoma (MTC) constitutes approximately 5 % of
      all thyroid cancers and carries a worse prognosis than other differentiated
      thyroid cancers. Targeted therapies are being investigated for systemic treatment
      of MTC. Ubiquitin-specific peptidase 39 (USP39) functions in pre-mRNA splicing as
      a component of the U4/U6-U5 tri-snRNP and also participates in spindle checkpoint
      and cytokinesis. In this study, we aimed to evaluate the potential role in MTC.
      METHODS: We used lentivirus-delivered short hairpin RNA (shRNA) to silence USP39
      expression in one MTC cell line TT. USP39 expression was detected by qPCR and
      Western blot. For functional analysis, MTT assay was performed to evaluate the
      proliferation activity, and FACS was used to assess the cell distribution in the
      cell cycle. Moreover, the expressions of cell cycle-related proteins were
      examined by Western blot. RESULTS: Both two shRNA sequences against USP39 could
      efficiently reduce its expression in TT cells. Knockdown of USP39 significantly
      decreased cell proliferation and caused cell cycle arrest at G2/M phase.
      Moreover, G2/M phase-associated proteins, Cyclin B1 and CDK1, were obviously down
      regulated in TT cells after USP39 silencing. CONCLUSIONS: Therefore, knockdown of
      USP39 is likely to provide a novel alternative to targeted therapy of MTC and
      deserves further investigation.

PMID- 26303215
TI  - Identification of miRNAs in Bovine Endometrium through RNAseq and Prediction of
      Regulated Pathways.
AB  - Detection of miRNAs in reproductive tissues is a key step to understand their
      role in fertility. We hypothesize that miRNAs must be involved in pathways
      controlling endometrial physiology and defense against pathogens. In this study,
      we aimed to characterize miRNAs present in bovine endometrium and to predict
      regulated pathways. Cytobrush endometrial samples from four cows were collected
      at oestrous cycle days 1-5, 6-12, 13-18 and 19-21. RNA was extracted and
      sequenced using Ion Torrent ((r)) technology. After mapping of the reads to miRNA
      stem loops, rRNAs and tRNAs, data were normalized and analysed using DESeq2.
      Targets and pathways were predicted with miRmap and KEGG, respectively.
      Validation of miRNAs in tissue was done by RT-qPCR (miR-Q). A total of 221
      identities were common among groups, accumulating more than 99% of miRNA
      expression. MiRNAs were predicted to regulate MAPK signalling pathway, lysosome
      and extracellular matrix (ECM)-receptor interaction. Eight miRNAs were validated
      by miR-Q, showing that let-7a-5p and let-7b were regulated across the oestrous
      cycle. This study demonstrated a high similarity in miRNA expression profile
      across the oestrous cycles in bovine endometrium. These miRNAs were predicted to
      regulate pathways involved in cell proliferation, differentiation, transport and
      catabolism. The number of pathways shared by different miRNAs indicates the broad
      range of regulation these molecules exhibit in the endometrium. 

PMID- 26303217
TI  - Correction.

PMID- 26303216
TI  - Testing two screening instruments for autism spectrum disorder in UK community
      child health services.
AB  - AIM: The aim of this study was to test the accuracy of two screening instruments
      in UK Community health services: Modified Checklist for Autism in Toddlers (M
      CHAT) and Social Communication Questionnaire (SCQ) for autism spectrum disorder
      (ASD). A two-stage screening and in-depth assessment procedure, combined with
      sampling stratification and statistical weighting, allowed the accuracy of the
      screens to be estimated in the entire population of referred children. METHOD:
      The study included all referrals of children aged 18 to 48 months to community
      paediatric and speech and language therapy services in two London districts over
      a 12-month period between September 2004 and September 2005. Parents of 808
      children were approached; screen data were obtained on 543 children (67.2%). A
      stratified subsample of 120 children received an in-depth assessment for ASD as
      defined by the International Statistical Classification of Diseases and Related
      Health Problems, 10th edition. Community clinician judgement of likely ASD was
      available for 98 out of the 120 children. RESULTS: The sensitivity and
      specificity were 64% (95% confidence intervals; range 51-80%) and 75% (63-85%)
      for the SCQ, and 82% (72-92%) and 50% (33-64%) for M-CHAT. There was no evidence
      that the area under the curve differed between the two screening instruments.
      There was also no evidence that clinician judgement of likely ASD differed from
      either of the screening tests. The screening tests did not perform well to
      confirm preliminary clinical judgement to refer (in series), nor as an
      alternative indicator for referral (in parallel). INTERPRETATION: While screening
      tests may provide useful information, their accuracy is moderate. Screening
      information in isolation should not be used to make referral decisions regarding
      specialized ASD assessment.

PMID- 26303218
TI  - MyD88-dependent pro-inflammatory activity in Vi polysaccharide vaccine against
      typhoid promotes Ab switching to IgG.
AB  - Vi capsular polysaccharide is currently in use as a vaccine against human typhoid
      caused by Salmonella Typhi. The vaccine efficacy correlates with IgG anti-Vi Abs.
      We have recently reported that Vi can generate inflammatory responses through
      activation of the TLR2/TLR1 complex. In the present study, we show that
      immunization with Vi produces IgM as well as IgG Abs in wild type mice. This
      ability is not compromised in mice deficient in T cells. However, immunization of
      mice lacking the TLR adaptor protein, MyD88, with Vi elicits only IgM Abs. These
      results suggest that MyD88-dependent pro-inflammatory ability of the Vi vaccine
      might be vital in generating IgG Abs with this T-independent Ag. 

PMID- 26303220
TI  - A pilot study on the impact of known drug-drug interactions in cancer patients.
AB  - BACKGROUND: When a patient concomitantly uses two or more drugs, a drug-drug
      interaction (DDI) can possibly occur, potentially leading to an increased or
      decreased clinical effect of a given treatment. Cancer patients are at high risk
      of such interactions because they commonly receive multiple medications.
      Moreover, most cancer patients are elderly and require additional medications for
      comorbidities. Aim of this preliminary observational study was to evaluate the
      incidence of well known and established DDIs in a cohort of cancer outpatients
      undergoing multiple treatments. METHODS: Anamnestic and clinical data were
      collected for 64 adult patients in the ambulatory setting with malignant solid
      tumors who were receiving systemic anticancer treatment. Patients also declared
      all drugs prescribed by other specialists or self-taken in the previous 2 weeks.
      DDIs were divided into two different groups: 'neoplastic DDIs' (NDDIs), involving
      antitumoral drugs, and 'not neoplastic DDIs' (nDDIs), involving all other classes
      of drugs. The severity of DDIs was classified as major, moderate and minor,
      according to the 'Institute for Pharmacological Research Mario Negri' definition.
      RESULTS: About 34 % of cancer outpatients within our cohort were
      prescribed/assumed interacting drug combinations. The most frequent major NDDIs
      involved the anticoagulant warfarin (33 % of total NDDIs) that, in association
      with tamoxifen, or capecitabine and paclitaxel, increased the risk of
      haemorrhage. About 60 % of nDDIs involved acetylsalicylic acid. CONCLUSIONS:
      Overall, 16 % of DDIs were related to an A-level strength of recommendation to be
      avoided. The lack of effective communication among specialists and patients might
      have a role in determining therapeutic errors. Our pilot study, although limited
      by a small cohort size, highlights the urgent need of implementing the clinical
      management of cancer outpatients with new strategies to prevent or minimize
      potential harmful DDIs.

PMID- 26303221
TI  - Intermittent PTH treatment can delay the transformation of mature osteoblasts
      into lining cells on the periosteal surfaces.
AB  - Mature osteoblasts have three fates: as osteocytes, quiescent lining cells, or
      osteoblasts that undergo apoptosis. However, whether intermittent parathyroid
      hormone (PTH) can modulate the fate of mature osteoblasts in vivo is uncertain.
      We performed a lineage-tracing study using an inducible gene system. Dmp1-CreERt2
      mice were crossed with Rosa26R reporter mice to obtain targeted mature
      osteoblasts and their descendants, lining cells or osteocytes, which were
      detected using X-gal staining. Rosa26R:Dmp1-CreERt2(+) mice were injected with
      0.25 mg 4-OH-tamoxifen (4-OHTam) on postnatal days 5, 7, 9, 16, and 23. In a
      previous study, at 22 days after the last 4-OHTam, most LacZ+ cells on the
      periosteal surface were inactive lining cells. On day 25 (D25), the mice were
      challenged with an injection of human PTH (1-34, 80 MUg/kg) or vehicle daily for
      10 (D36) or 20 days (D46). We evaluated the number and thickness of LacZ+
      osteoblast descendants in the calvaria and tibia. In the vehicle group, the
      number and thickness of LacZ+ osteoblast descendants at both D36 and D46
      significantly decreased compared to D25, which was attenuated in the PTH group.
      In line with these results, PTH inhibited the decrease in the number of
      LacZ+/osteocalcin-positive cells compared to vehicle at both D36 and D46. As
      well, the serum levels of sclerostin decreased, as did the protein expression of
      sclerostin in the cortical bone. These results suggest that intermittent PTH
      treatment can increase the number of periosteal osteoblasts by preventing mature
      osteoblasts from transforming into lining cells in vivo. 

PMID- 26303219
TI  - A systematic review of the relationship between subchondral bone features, pain
      and structural pathology in peripheral joint osteoarthritis.
AB  - INTRODUCTION: Bone is an integral part of the osteoarthritis (OA) process. We
      conducted a systematic literature review in order to understand the relationship
      between non-conventional radiographic imaging of subchondral bone, pain,
      structural pathology and joint replacement in peripheral joint OA. METHODS: A
      search of the Medline, EMBASE and Cochrane library databases was performed for
      original articles reporting association between non-conventional radiographic
      imaging-assessed subchondral bone pathologies and joint replacement, pain or
      structural progression in knee, hip, hand, ankle and foot OA. Each association
      was qualitatively characterised by a synthesis of the data from each analysis
      based upon study design, adequacy of covariate adjustment and quality scoring.
      RESULTS: In total 2456 abstracts were screened and 139 papers were included (70
      cross-sectional, 71 longitudinal analyses; 116 knee, 15 hip, six hand, two ankle
      and involved 113 MRI, eight DXA, four CT, eight scintigraphic and eight 2D shape
      analyses). BMLs, osteophytes and bone shape were independently associated with
      structural progression or joint replacement. BMLs and bone shape were
      independently associated with longitudinal change in pain and incident frequent
      knee pain respectively. CONCLUSION: Subchondral bone features have independent
      associations with structural progression, pain and joint replacement in
      peripheral OA in the hip and hand but especially in the knee. For peripheral OA
      sites other than the knee, there are fewer associations and independent
      associations of bone pathologies with these important OA outcomes which may
      reflect fewer studies; for example the foot and ankle were poorly studied.
      Subchondral OA bone appears to be a relevant therapeutic target. SYSTEMATIC
      REVIEW: PROSPERO registration number: CRD 42013005009.

PMID- 26303222
TI  - Comparison of the effects of 12 months of monthly minodronate monotherapy and
      monthly minodronate combination therapy with vitamin K2 or eldecalcitol in
      patients with primary osteoporosis.
AB  - The aim of this observational, nonrandomized study was to compare the effects of
      12 months of monthly minodronate (MIN; 50 mg/month) monotherapy and MIN
      combination therapy with vitamin K2 (VK; 45 mg/day) or eldecalcitol (ELD; 0.75
      MUg/day) in treatment-naive patients with primary osteoporosis. Patients (n =
      193; 178 postmenopausal women and 15 men; mean age 71.6 years) were treated with
      (1) MIN monotherapy (n = 63), (2) MIN plus VK combination therapy (n = 50), or
      (3) MIN plus ELD combination therapy (n = 80) for 12 months. Changes in bone
      mineral density (BMD) and the levels of serum bone turnover markers were
      monitored. No significant difference was observed in baseline BMD among the three
      groups. After 12 months, BMD increased by 2.93, 4.65, and 6.55 % in the lumbar
      spine, 0.66, 2.57, and 3.42 % in the total hip, and 0.05, 2.06, and 3.58 % in the
      femoral neck in groups 1, 2, and 3, respectively. The BMD increase induced by MIN
      plus ELD combination therapy was significantly greater than that induced by MIN
      monotherapy in the lumbar spine (P = 0.0002), total hip (P = 0.003), and femoral
      neck (P = 0.004), and also that induced by MIN plus VK combination therapy in the
      lumbar spine (P = 0.03). MIN plus ELD combination therapy compared with MIN
      monotherapy resulted in a greater decrease in serum procollagen type I N-terminal
      propeptide levels (-37.4 % vs -54.6 %; P = 0.001) and tartrate-resistant acid
      phosphatase isoform 5b levels (-41.1 % vs -52.9 %; P = 0.009) at 3 months, and a
      greater decrease in procollagen type I N-terminal propeptide levels (-64.3 % vs 
      50.3 %; P = 0.03) and a decrease in intact parathyroid hormone levels (-12.3 % vs
      14.0 %; P = 0.01) at 12 months. Combination therapy with MIN and VK or ELD for 12
      months showed additive effects in decreasing the levels of bone turnover markers
      compared with MIN monotherapy, whereas MIN plus ELD combination therapy resulted
      in the highest BMD increase compared with MIN monotherapy and MIN plus VK
      combination therapy. 

PMID- 26303223
TI  - Analysis of the Japanese Diabetes Risk Score and fatty liver markers for incident
      diabetes in a Japanese cohort.
AB  - AIMS: We examined the effectiveness of the Japanese Diabetes Risk Score (JPDRISC)
      and fatty liver markers for predicting incident diabetes. METHODS: We created the
      JPDRISC. The study periods I and II were January 2007 to May 2009 and June 2009
      to December 2011, respectively. A total of 2084 people (1389 men, 695 women; mean
      age: 46 years) were included. People with diabetes in the Period I and those with
      ethanol intake >140 g/week were excluded. A total of 1515 people were included.
      Fatty liver using ultrasonography scores (FLUS) were assigned. RESULTS: The mean
      observation period was 26.3 months, and 24 people had developed diabetes between
      the Periods I and II. In logistic regression analysis, the JPDRISC (OR=1.197, 95%
      C.I.: 1.062-1.350, p=0.003) and FLUS (OR=2.591, 95% C.I.: 1.411-4.758, p=0.002)
      in the Period I were independent determinants of incident diabetes. In receiver
      operating characteristic analysis, sensitivity and specificity for incident
      diabetes were 0.885 and 0.536, respectively, in people with both FLUS>=1 and the
      total JPDRISC>=6 in the Period I. The sensitivity was better than the JPDRISC
      alone (sensitivity 0.696) and FLUS alone (sensitivity 0.750). CONCLUSIONS:
      JPDRISC and FLUS were independently associated with incident diabetes and their
      combination is useful.

PMID- 26303225
TI  - PARP inhibitor maintenance therapy for patients with platinum-sensitive recurrent
      ovarian cancer: a cost-effectiveness analysis.
AB  - PURPOSE: To determine the cost-effectiveness of olaparib, a PARP inhibitor, as
      maintenance therapy for platinum-sensitive (PS) recurrent ovarian cancer.
      METHODS: Two separate decision analysis models compared the cost of observation
      versus olaparib maintenance therapy in patients with PS recurrent ovarian cancer,
      one for patients with a germline BRCA1/2 mutation and one for patients with wild
      type BRCA1/2. Patients received six cycles of paclitaxel and carboplatin. Drug
      costs were estimated using 2014-2015 wholesale acquisition costs. The cost of
      olaparib was estimated at $13,440 per month. Rate of germline BRCA1/2 mutation
      was estimated at 20%. Progression-free survival was determined from published
      data. Incremental cost-effectiveness ratios (ICERs) per progression-free life
      year saved (PF-LYS) were calculated. A sensitivity analysis estimated the cost at
      which olaparib would be cost-effective. RESULTS: We estimated that there were
      5549 patients diagnosed with PS recurrent ovarian cancer in the United States
      annually. The cost of observation in 1110 patients with a BRCA1/2 mutation was
      $5.5 million (M) versus $169.2M for maintenance therapy with olaparib. The ICER
      for olaparib maintenance therapy in patients with a BRCA mutation was $258,864
      per PF-LYS. If the cost of olaparib was decreased to $2500 per month, the ICER
      was $49,584. For the 4439 patients with wild-type BRCA, the cost of maintenance
      therapy was $444.2M; the ICER was $600,552 per PF-LYS. CONCLUSIONS: For patients
      with a germline BRCA1/2 mutation, maintenance therapy with olaparib is not cost
      effective with an ICER of $258,864 per PF-LYS. To achieve an ICER of less than
      $50,000, the cost of olaparib should be $2500 or less per month. For wild-type
      BRCA1/2 patients, maintenance therapy with olaparib is not cost-effective.

PMID- 26303226
TI  - Identification of Amino Acid Residues in Angiotensin II Type 1 Receptor Sensing
      Mechanical Stretch and Function in Cardiomyocyte Hypertrophy.
AB  - BACKGROUND/AIMS: Angiotensin II (AngII) type 1 receptor (AT1R) could be activated
      by mechanical stress without the involvement of AngII during the development of
      cardiac hypertrophy. We aimed to identify sensing sites of AT1R for activation by
      mechanical stretch. METHODS: We constructed several site-directed mutations of
      AT1R (AT1R(K199Q), AT1R(L212F), AT1R(Q257A) and AT1R(C289A)), transfected them
      respectively into COS7 cells or angiotensinogen knockout cardiomyocytes (ATG(-/-)
      CMs), and observed cellular events after mechanical stretch. RESULTS: AngII
      induced phosphorylation of ERKs and Jak2, and redistribution of Galphaq11 in
      AT1R(WT)- COS7 or -ATG(-/-)-CMs were dramatically decreased in AT1R(K199Q)- or
      AT1R(Q257A)- COS7 cells or -ATG(-/-)- CMs, while those effects induced by
      mechanical stretch were greatly suppressed in COS7 cells or ATG(-/-)-CMs
      expressing AT1R(L212F), AT1R(Q257A) or AT1R(C289A) compared with these cells
      expressing AT1R(WT). AngII-induced hypertrophic responses (the increase in
      hypertrophic genes expression and cross-sectional area) in AT1R(WT)- ATG(-/-)-CMs
      were partly abolished in AT1R(K199Q)-ATG(-/-)- CMs or AT1R(Q257A) -ATG(-/-)-CMs,
      while these responses induced by mechanical stretch were greatly inhibited in
      ATG(-/-)-CMs overexpressing AT1R(L212F), AT1R(Q257A )or AT1R(C289A). CONCLUSION:
      These results indicated that Leu212, Gln257 and Cys289 in AT1R are not only
      sensing sites for mechanical stretch but also functional amino residues for
      activation of the receptor and cardiomyocytes hypertrophy induced by mechanical
      stretch.

PMID- 26303224
TI  - Cortical brain atrophy and intra-individual variability in neuropsychological
      test performance in HIV disease.
AB  - To characterize the relationship between dispersion-based intra-individual
      variability (IIVd) in neuropsychological test performance and brain volume among
      HIV seropositive and seronegative men and to determine the effects of
      cardiovascular risk and HIV infection on this relationship. Magnetic Resonance
      Imaging (MRI) was used to acquire high-resolution neuroanatomic data from 147 men
      age 50 and over, including 80 HIV seropositive (HIV+) and 67 seronegative
      controls (HIV-) in this cross-sectional cohort study. Voxel Based Morphometry was
      used to derive volumetric measurements at the level of the individual voxel.
      These brain structure maps were analyzed using Statistical Parametric Mapping
      (SPM2). IIVd was measured by computing intra-individual standard deviations
      (ISD's) from the standardized performance scores of five neuropsychological
      tests: Wechsler Memory Scale-III Visual Reproduction I and II, Logical Memory I
      and II, Wechsler Adult Intelligence Scale-III Letter Number Sequencing. Total
      gray matter (GM) volume was inversely associated with IIVd. Among all subjects,
      IIVd -related GM atrophy was observed primarily in: 1) the inferior frontal gyrus
      bilaterally, the left inferior temporal gyrus extending to the supramarginal
      gyrus, spanning the lateral sulcus; 2) the right superior parietal lobule and
      intraparietal sulcus; and, 3) dorsal/ventral regions of the posterior section of
      the transverse temporal gyrus. HIV status, biological, and cardiovascular disease
      (CVD) variables were not linked to IIVd -related GM atrophy. IIVd in
      neuropsychological test performance may be a sensitive marker of cortical
      integrity in older adults, regardless of HIV infection status or CVD risk
      factors, and degree of intra-individual variability links with volume loss in
      specific cortical regions; independent of mean-level performance on
      neuropsychological tests.

PMID- 26303227
TI  - Oligogenic inheritance of optineurin (OPTN) and C9ORF72 mutations in ALS
      highlights localisation of OPTN in the TDP-43-negative inclusions of C9ORF72-ALS.
AB  - Amyotrophic lateral sclerosis (ALS) is characterized by motor neurone loss
      resulting in muscle weakness, spasticity and ultimately death. 5-10% are caused
      by inherited mutations, most commonly C9ORF72, SOD1, TARDBP and FUS. Rarer
      genetic causes of ALS include mutation of optineurin (mt OPTN). Furthermore,
      optineurin protein has been localized to the ubiquitylated aggregates in several
      neurodegenerative diseases, including ALS. This study: (i) investigated the
      frequency of mt OPTN in ALS patients in England; (ii) characterized the clinical
      and neuropathological features of ALS associated with a mt OPTN; and (iii)
      investigated optineurin neuropathology in C9ORF72-related ALS (C9ORF72-ALS). We
      identified a heterozygous p.E322K missense mutation in exon 10 of OPTN in one
      familial ALS patient who additionally had a C9ORF72 mutation. This patient had
      bulbar, limb and respiratory disease without cognitive problems. Neuropathology
      revealed motor neurone loss, trans-activation response DNA protein 43 (TDP-43)
      positive neuronal and glial cytoplasmic inclusions together with TDP-43-negative
      neuronal cytoplasmic inclusions in extra motor regions that are characteristic of
      C9ORF72-ALS. We have demonstrated that both TDP-43-positive and negative
      inclusion types had positive staining for optineurin by immunohistochemistry. We
      went on to show that optineurin was present in TDP-43-negative cytoplasmic extra
      motor inclusions in C9ORF72-ALS cases that do not carry mt OPTN. We conclude
      that: (i) OPTN mutations are associated with ALS; (ii) optineurin protein is
      present in a subset of the extramotor inclusions of C9ORF72-ALS; (iii) It is not
      uncommon for multiple ALS-causing mutations to occur in the same patient; and
      (iv) studies of optineurin are likely to provide useful dataregarding the
      pathophysiology of ALS and neurodegeneration. 

PMID- 26303228
TI  - Assessment of colon and bladder crosstalk in an experimental colitis model using
      contrast-enhanced magnetic resonance imaging.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) consists of two chronic remitting
      relapsing inflammatory disorders in the colon referred to as ulcerative colitis
      and Crohn's disease (CD). Inflammatory bowel disease affects about 1.4 million
      Americans. 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis is a widely
      used model of experimental intestinal inflammation with characteristic transmural
      and segmental lesions that are similar to CD. METHODS: Here, we report on the use
      of contrast-enhanced magnetic resonance imaging (CE-MRI) to monitor in vivo
      bladder permeability changes resulting from bladder crosstalk following colon
      TNBS exposure, and TNBS-induced colitis. Changes in MRI signal intensities and
      histology were evaluated for both colon and bladder regions. KEY RESULTS: Uptake
      of contrast agent in the colon demonstrated a significant increase in signal
      intensity (SI) for TNBS-exposed rats (p < 0.01) compared to controls. In
      addition, a significant increase in bladder SI for colon TNBS-exposed rats (p <
      0.001) was observed compared to saline controls. Histological damage within the
      colon was observed, however, bladder histology indicated a normal urothelium in
      rats with TNBS-induced colitis, despite increased permeability seen by CE-MRI.
      CONCLUSIONS & INFERENCES: Contrast-enhanced MRI was able to quantitatively
      measure inflammation associated with TNBS-induced colitis, and assess bladder
      crosstalk measured as an increase in urothelial permeability. Although CE-MRI is
      routinely used to assess inflammation with IBD, currently there is no diagnostic
      test to assess bladder crosstalk with this disease, and our developed method may
      be useful in providing crosstalk information between organ and tissue systems in
      IBD patients, in addition to colitis.

PMID- 26303229
TI  - The Temporal Dynamics of Regularity Extraction in Non-Human Primates.
AB  - Extracting the regularities of our environment is one of our core cognitive
      abilities. To study the fine-grained dynamics of the extraction of embedded
      regularities, a method combining the advantages of the artificial language
      paradigm (Saffran, Aslin, & Newport, ) and the serial response time task (Nissen
      & Bullemer, ) was used with a group of Guinea baboons (Papio papio) in a new
      automatic experimental device (Fagot & Bonte, ). After a series of random trials,
      monkeys were exposed to language-like patterns. We found that the extraction of
      embedded patterns positioned at the end of larger patterns was faster than the
      extraction of initial embedded patterns. This result suggests that there is a
      learning advantage for the final element of a sequence that benefits from the
      contextual information provided by previous elements. 

PMID- 26303230
TI  - Home parenteral nutrition is beneficial in systemic sclerosis patients with
      gastrointestinal dysfunction.
AB  - OBJECTIVES: To assess 12-month changes in nutritional status and quality of life
      (QoL) in systemic sclerosis (SSc) patients requiring home parenteral nutrition
      (HPN). METHOD: We conducted a retrospective, single-centre database analysis of
      SSc patients regarding a 12-month period of HPN at an interdisciplinary
      University Unit/team for nutrition and rheumatic diseases. Nutritional status was
      analysed by nutritional risk screening (NRS) and body mass index (BMI). QoL was
      evaluated using Short-Form Health Survey (SF-36) questionnaires. RESULTS: Between
      2008 and 2013, daily nocturnal HPN was initiated in five consecutive SSc patients
      (four females and one male, mean age 62.2 years) suffering severe malnutrition
      due to gastrointestinal tract (GIT) involvement. After 12 months of HPN, the mean
      NRS score decreased from 4.4 (range 4-5) to 1.4 (range 1-2), the mean BMI
      increased from 19.1 (range 17.4-20.3) to 21.0 kg/m2 (range 18.3-23.4). QoL
      improved in all patients, reflected by the summary of physical components with
      33.92 points before vs. 67.72 points after 12 months of HPN, and the summary of
      mental components with 49.66 points before vs. 89.27 points after 12 months of
      HPN. Two patients suffered one catheter-related infection each with subsequent
      surgical removal and reinsertion. CONCLUSIONS: HPN is a feasible method for
      improving anthropometric parameters and QoL in SSc patients severely affected by
      GIT dysfunction. We recommend HPN in malnourished, catabolic SSc patients unable
      to otherwise maintain or improve their nutritional status.

PMID- 26303231
TI  - Beta blockade increases pulmonary and systemic transit time heterogeneity:
      evaluation based on indocyanine green kinetics in healthy volunteers.
AB  - Knowledge of factors influencing the heterogeneity of blood transit times is
      important in cardiovascular physiology. The aim of the study was to investigate
      the effect of beta-adrenergic blockade on blood transit time dispersion in awake,
      anxious volunteers. Recirculatory modelling of the disposition of intravascular
      markers using parametric forms for transit time distributions, such as the
      inverse Gaussian distribution, provides the opportunity to estimate the systemic
      and pulmonary transit time dispersion in vivo. The latter is determined by the
      flow heterogeneity in the microcirculatory network. Using this approach, we have
      analysed indocyanine green (ICG) disposition data obtained in four subjects by
      frequent early arterial blood sampling before and after beta-adrenergic blockade
      by propranolol. Propranolol decreased cardiac output from 9.3 +/- 2.8 l min-1 to
      3.5 +/- 0.47 l min-1 (P<0.05). This reduction was accompanied by a 4.5 +/- 0.6
      fold and 2.1 +/- 0.3-fold increase (P<0.001) in the relative dispersion
      (dimensionless variance) of blood transit times through the systemic and
      pulmonary circulation, respectively.

PMID- 26303232
TI  - Niels Keiding 70 years.

PMID- 26303233
TI  - The pap smear caught it!: Harmonizing the findings of an abnormal pap smear and a
      right ovarian mass.

PMID- 26303234
TI  - Fas-Associated Protein with Death Domain Regulates Notch Signaling during Muscle
      Regeneration.
AB  - Notch signaling plays critical roles during myogenesis by promoting the
      proliferation and inhibiting the differentiation of myogenic progenitors.
      However, the mechanism of the temporal regulation of Notch signaling during the
      myogenic lineage progression remains elusive. In the present study, we show that
      a constitutively phosphoryl-mimicking mutation of Fas-associated death domain
      (FADD-D) enhances Notch-1 signaling and compromises Wnt signaling in both
      cultured myoblasts and regenerating muscles, which results in inhibited myogenic
      differentiation and muscle regeneration. Inhibition of Notch signaling recovers
      the regeneration ability in injured FADD-D muscles through rescuing Wnt
      signaling. Furthermore, we found that protein kinase Calpha mediates FADD-D
      induced Notch-1 signaling by stabilizing Notch-1. Collectively, these data
      identify a novel mechanism for the temporal regulation of Notch signaling during
      myogenic lineage progression and muscle regeneration.

PMID- 26303236
TI  - The Analytical Chemistry virtual issue featuring our advisory boards.

PMID- 26303235
TI  - Luteipulveratus halotolerans sp. nov., an actinobacterium (Dermacoccaceae) from
      forest soil.
AB  - The taxonomic position of an actinobacterium strain, C296001T, isolated from a
      soil sample collected in Sarawak, Malaysia, was established using a polyphasic
      approach. Phylogenetically, strain C296001T was closely associated with the genus
      Luteipulveratus and formed a distinct monophyletic clade with the only described
      species, Luteipulveratus mongoliensis NBRC 105296T. The 16S rRNA gene sequence
      similarity between strain C296001T and L. mongoliensis was 98.7 %. DNA-DNA
      hybridization results showed that the relatedness of strain C296001T to L.
      mongoliensis was only 21.5 %. The DNA G+C content of strain C296001T was 71.7
      mol%. Using a PacBio RS II system, whole genome sequences for strains C296001T
      and NBRC 105296T were obtained. The genome sizes of 4.5 Mbp and 5.4 Mbp
      determined were similar to those of other members of the family Dermacoccaceae.
      The cell-wall peptidoglycan contained lysine, alanine, aspartic acid, glutamic
      acid and serine, representing the peptidoglycan type A4alpha l-Lys-l-Ser-d-Asp.
      The major menaquinones were MK-8(H4), MK-8 and MK-8(H2). Phosphatidylglycerol,
      phosphatidylinositol, diphosphatidylglycerol and phosphoglycolipid were the polar
      lipids, while the whole-cell sugars were glucose, fucose and lesser amounts of
      ribose and galactose. The major fatty acids were iso-C16 : 0, anteiso-C17 : 0,
      iso-C16 : 1 H, anteiso-C17 : 1omega9c, iso-C18 : 0 and 10-methyl C17 : 0.
      Chemotaxonomic analyses showed that C296001T had typical characteristics of
      members of the genus Luteipulveratus, with the main differences occurring in
      phenotypic characteristics. On the basis of the phenotypic and chemotaxonomic
      evidence, it is proposed that strain C296001T be classified as a representative
      of a novel species in the genus Luteipulveratus, for which the name
      Luteipulveratus halotolerans sp. nov. is recommended. The type strain is C296001T
      ( = ATCC TSD-4T = JCM 30660T).

PMID- 26303237
TI  - Performance Evaluation of Three URiSCAN Devices for Routine Urinalysis.
AB  - BACKGROUND: This study compares the diagnostic performance (in routine
      urinalysis) of three URiSCAN devices and three Roche analyzers to manual
      microscopy and quantitative assays. METHODS: We analyzed eight dipstick tests
      using three URiSCAN devices. The results were compared to those of the tests
      performed using three Roche analyzers. The results of leukocyte and erythrocyte
      screens were compared to those obtained using manual microscopy. Protein,
      glucose, pH, and specific gravity (SG) assays performed on the URiSCAN devices
      were compared with the results of corresponding quantitative assays. RESULTS: The
      rates of agreement within one grade difference were found to be more than 94.3%.
      When compared with manual microscopy, the Optima provided better diagnostic
      performance for the detection of leukocytes compared with the Urisys 1100.
      Compared to the Urisys 2400, the Super plus provided better diagnostic
      performance with regard to both leukocytes and erythrocytes. There was good
      correlation between the three URiSCAN devices and each quantitative assay, except
      for SG detection. CONCLUSION: There were well correlated results between those of
      the three URiSCAN devices and those obtained using the corresponding Roche
      analyzers, quantitative assays, and manual microscopy. URiSCAN series devices are
      therefore suitable for routine urinalysis in clinical laboratories.

PMID- 26303239
TI  - Broad and deep.

PMID- 26303238
TI  - Malaria Diagnosis Using a Mobile Phone Polarized Microscope.
AB  - Malaria remains a major global health burden, and new methods for low-cost, high
      sensitivity, diagnosis are essential, particularly in remote areas with low
      resource around the world. In this paper, a cost effective, optical cell-phone
      based transmission polarized light microscope system is presented for imaging the
      malaria pigment known as hemozoin. It can be difficult to determine the presence
      of the pigment from background and other artifacts, even for skilled microscopy
      technicians. The pigment is much easier to observe using polarized light
      microscopy. However, implementation of polarized light microscopy lacks
      widespread adoption because the existing commercial devices have complicated
      designs, require sophisticated maintenance, tend to be bulky, can be expensive,
      and would require re-training for existing microscopy technicians. To this end, a
      high fidelity and high optical resolution cell-phone based polarized light
      microscopy system is presented which is comparable to larger bench-top polarized
      microscopy systems but at much lower cost and complexity. The detection of
      malaria in fixed and stained blood smears is presented using both, a conventional
      polarized microscope and our cell-phone based system. The cell-phone based
      polarimetric microscopy design shows the potential to have both the resolution
      and specificity to detect malaria in a low-cost, easy-to-use, modular platform. 

PMID- 26303240
TI  - Woringer-Kolopp disease mimicking psoriasis.

PMID- 26303241
TI  - Malaria vaccine not perfect, but still useful.

PMID- 26303242
TI  - Tianjin chemical clean-up after explosion.

PMID- 26303243
TI  - Doctors call for divestment from fossil fuels.

PMID- 26303245
TI  - Residency cuts reveal workforce plan flaws.

PMID- 26303244
TI  - Outcomes of deliveries by family physicians or obstetricians: a population-based
      cohort study using an instrumental variable.
AB  - BACKGROUND: Previous research has suggested that obstetric outcomes are similar
      for deliveries by family physicians and obstetricians, but many of these studies
      were small, and none of them adjusted for unmeasured selection bias. We compared
      obstetric outcomes between these provider types using an econometric method
      designed to adjust for unobserved confounding. METHODS: We performed a
      retrospective population-based cohort study of all Canadian (except Quebec)
      hospital births with delivery by family physicians and obstetricians at more than
      20 weeks gestational age, with birth weight greater than 500 g, between Apr. 1,
      2006, and Mar. 31, 2009. The primary outcomes were the relative risks of in
      hospital perinatal death and a composite of maternal mortality and major
      morbidity assessed with multivariable logistic regression and instrumental
      variable-adjusted multivariable regression. RESULTS: After exclusions, there were
      3600 perinatal deaths and 14,394 cases of maternal morbidity among 799,823
      infants and 793,053 mothers at 390 hospitals. For deliveries by family physicians
      v. obstetricians, the relative risk of perinatal mortality was 0.98 (95%
      confidence interval [CI] 0.85-1.14) and of maternal morbidity was 0.81 (95% CI
      0.70-0.94) according to logistic regression. The respective relative risks were
      0.97 (95% CI 0.58-1.64) and 1.13 (95% CI 0.65-1.95) according to instrumental
      variable methods. INTERPRETATION: After adjusting for both observed and
      unobserved confounders, we found a similar risk of perinatal mortality and
      adverse maternal outcome for obstetric deliveries by family physicians and
      obstetricians. Whether there are differences between these groups for other
      outcomes remains to be seen.

PMID- 26303246
TI  - Hepatitis C virus infection.

PMID- 26303248
TI  - A 26-year-old competitive soccer player with syncope.

PMID- 26303249
TI  - Hepatitis C virus infection: accessing drug treatment.

PMID- 26303247
TI  - Reducing pain during vaccine injections: clinical practice guideline.

PMID- 26303250
TI  - Regulation of Large Conductance Voltage-and Ca2+-Activated K+ Channels by the
      Janus Kinase JAK3.
AB  - BACKGROUND/AIMS: Janus kinase 3 (JAK3), a tyrosine kinase contributing to the
      regulation of cell proliferation and apoptosis of lymphocytes and tumour cells,
      has been shown to modify the expression and function of several ion channels and
      transport proteins. Channels involved in the regulation of cell proliferation
      include the large conductance voltage- and Ca(2+)-activated K(+) channel BK. The
      present study explored whether JAK3 modifies BK channel protein abundance and
      current. METHODS: cRNA encoding Ca(2+)-insensitive BK channel (BK(M513I+Delta899
      903)) was injected into Xenopus oocytes with or without additional injection of
      cRNA encoding wild-type JAK3, constitutively active A568VJAK3, or inactive
      (K851A)JAK3. Voltage gated K(+ )channel activity was measured utilizing dual
      electrode voltage clamp. Moreover, BK channel protein abundance was determined
      utilizing flow cytometry in CD19(+) B lymphocyte cell membranes from mice lacking
      functional JAK3 (jak3(-/-)) and corresponding wild-type mice (jak3(+/+)).
      RESULTS: BK activity in BK(M513I+Delta899-903) expressing oocytes was slightly
      but significantly decreased by coexpression of wild-type JAK3 and of (A568V)JAK3,
      but not by coexpression of (K851A)JAK3. The BK channel protein abundance in the
      cell membrane was significantly higher in jak3(-/-) than in jak3(+/+) B
      lymphocytes. The decline of conductance in BK and JAK3 coexpressing oocytes
      following inhibition of channel protein insertion by brefeldin A (5 uM) was
      similar in oocytes expressing BK with JAK3 and oocytes expressing BK alone,
      indicating that JAK3 might slow channel protein insertion into rather than
      accelerating channel protein retrieval from the cell membrane. CONCLUSION: JAK3
      is a weak negative regulator of membrane BK protein abundance and activity.

PMID- 26303251
TI  - New phenolic compounds from the lichen Parmotrema praesorediosum (Nyl.) Hale
      (Parmeliaceae).

PMID- 26303252
TI  - Deluge of responses to India's draft law delays stricter tobacco controls.

PMID- 26303253
TI  - Self-Rated Health and Associated Factors in Older Turkish Adults With Type 2
      Diabetes: A Pilot Study.
AB  - PURPOSE: To evaluate self-rated health (SRH) and determine its associations with
      participant characteristics, glycemic control, family support, and health-related
      quality of life in older Turkish adults with type 2 diabetes. METHOD: This cross
      sectional study included 113 adults aged 60 years or older with type 2 diabetes.
      Data were collected by using an information form, the Perceived Social Support
      From Family Scale, and the Nottingham Health Profile. SRH was assessed by a
      single-item question. Glycemic control was measured by glycosylated hemoglobin
      levels. RESULTS: Ninety-seven patients (85.8%) evaluated their health as fair or
      poor. The glycemic target level (glycosylated hemoglobin <7.5%) was achieved in
      47.8% of the patients. Female gender, a low or moderate family income, and lower
      levels of family support were associated with poorer SRH.
      CONCLUSIONS/IMPLICATIONS: The majority of the participants considered their
      health to be fair or poor. Better understanding of risk factors associated with
      SRH may provide more effective interventions to improve health outcomes.

PMID- 26303254
TI  - Office Chromatography: Precise printing of sample solutions on miniaturized thin
      layer phases and utilization for scanning Direct Analysis in Real Time mass
      spectrometry.
AB  - Office Chromatography combines achievements in office technologies with
      miniaturized planar chromatography. In the life sciences, printing of materials
      became an accepted technique, whereas in separation science, the use of printers
      for chromatography is at its infancy. A bubble-jet printer was modified for exact
      application on miniaturized plates. Technical modifications included the removal
      of all unnecessary parts and the improvement of the positioning system, purge
      unit and sample supply system. Evaluation was performed via a slide scanner and
      image evaluation software. Printing of a food dye mixture solution (n=5) led to a
      calculated mean deposition volume of 13+/-1nL/mm(2) per print-cycle. A mean
      determination coefficient (R(2); n=5) of 0.9990 was obtained for application of
      increasing volumes, executed via increasing band widths of 50-200MUm
      (corresponding to 2-8nL). Using larger band widths and multiple print jobs,
      deposition volumes of up to the microliter scale represented an alternative to
      cost-intensive standard equipment. After print, separation, detection and digital
      evaluation of five food dyes, mean R(2) (n=5) were obtained between 0.9977 and
      0.9995. The accuracy of printing was proven by mean recovery rates of 101-105%
      with repeatabilities of 3-7% (%RSD, n=5). The transfer to nanostructured
      ultrathin-layer plates proved the synergetic potential of these fields of
      research. First, this modified printer was suited for printing of finely
      graduated scales of three preservatives for determination of the spatial
      resolution of scanning Direct Analysis in Real Time mass spectrometry. 

PMID- 26303255
TI  - Radical-mediated step-growth: Preparation of hybrid polymer monolithic columns
      with fine control of nanostructural and chromatographic characteristics.
AB  - The currently most successful type of porous polymer monoliths utilized in
      chromatography is prepared by free-radical cross-linking (co)polymerization in
      porogenic solvents and a single-step molding process. Though such types of
      materials are well-recognized in the scientific community, they suffer from their
      multi-scale heterogeneity originating from the nanoscale through to their
      microscale and ultimately limited performance on their macroscale. This is in
      particular true when estimating their performance under equilibrium (i.e.
      isocratic) elution conditions for retained compounds. In this contribution, we
      study a new concept in the preparation of porous monolithic hybrid materials
      based on polyhedral oligomeric vinylsilsesquioxanes which undergo radical
      mediated step-growth cross-linking with thiol-linkers. Fundamental
      characterization of this new entry of materials is performed via a variety of
      characterization approaches including infrared and Raman spectroscopies,
      thermogravimetric analysis, gel fraction, dry-state surface area analysis, and
      visualization of the capillary-scale porous structure by scanning electron
      microscopy. This characterization identifies that a rational choice of
      experimental conditions in monolith preparation leads to destined and desirable
      materials' properties, in particular with experimentally accessible near-ideal
      nanoscale network structures. With the obtained structural informations at hand,
      we finally evidence the monoliths' tailored chromatographic performance by
      isocratic elution experiments of structurally similar small molecules under
      reversed-phase type of chromatographic conditions. This validates the fundamental
      origin for an improved performance of these types of monolithic materials under
      solvated conditions that has its foundation established in the creation of near
      ideal nanoscale networks of material. This identified ideality is manifested in
      an enhanced and almost retention-insensitive performance in liquid
      chromatographic separations of small molecules across wide ranges of retention
      factors over at least two orders of magnitude and wide ranges of mobile phase
      compositions. Such experimental observation is explained by a more homogeneous
      energetic distribution of partition and adsorption sites. A reference analysis of
      normalized plate height data at varied retention was performed and set in context
      with data of state-of-the-art silica- and polymer-based monoliths. This analysis
      clearly identifies the present materials to display performance behavior clearly
      located in the domain of derivatized silica-based monoliths. 

PMID- 26303258
TI  - Synthesis of 2- and 6-thienylazulenes by palladium-catalyzed direct arylation of
      2- and 6-haloazulenes with thiophene derivatives.
AB  - Preparation of 2- and 6-thienylazulene derivatives was established by the
      palladium-catalyzed direct cross-coupling reaction of 2- and 6-haloazulenes with
      the corresponding thiophene derivatives in good yield. Several thienylazulene
      derivatives were also used in the reaction with 2-chloroazulene derivatives in
      the presence of the palladium-catalyst to afford the thiophene derivatives with
      two azulene functions in good yield. 

PMID- 26303257
TI  - The exercise-regulated myokine chitinase-3-like protein 1 stimulates human
      myocyte proliferation.
AB  - AIM: Chitinase-3-like protein 1 (CHI3L1) is involved in tissue remodelling and
      inflammatory processes. Plasma levels are elevated in patients with insulin
      resistance and T2DM. We recently showed that CHI3L1 and its receptor protease
      activated receptor 2 (PAR-2) are expressed in skeletal muscle. Activation of PAR
      2 by CHI3L1 protects against TNF-alpha-induced inflammation and insulin
      resistance. However, the effect of exercise on CHI3L1 and PAR-2 signalling
      remains unknown. The aim of this work was to study the impact of exercise on
      CHI3L1 production and the effect of CHI3L1/PAR-2 signalling on skeletal muscle
      growth and repair. METHODS: Three human exercise studies were used to measure
      CHI3L1 plasma levels (n = 32). In addition, muscle and adipose tissue CHI3L1 mRNA
      expression was measured in response to acute and long-term exercise (n = 24).
      Primary human skeletal muscle cells were differentiated in vitro, and electrical
      pulse stimulation was applied. In addition, myoblasts were incubated with CHI3L1
      protein and activation of MAP kinase signalling as well as proliferation was
      measured. RESULTS: Circulating CHI3L1 levels and muscle CHI3L1 mRNA were
      increased after acute exercise. In addition, CHI3L1 mRNA expression as well as
      CHI3L1 secretion was enhanced in electrically stimulated cultured myotubes.
      Incubation of cultured human myoblasts with CHI3L1 protein leads to a strong
      activation of p44/42, p38 MAPK and Akt as well as enhanced myoblast
      proliferation. CONCLUSION: Our findings suggest that CHI3L1 is induced by acute
      exercise and that CHI3L1/PAR-2 signalling activates myocyte proliferation, which
      is important for restructuring of skeletal muscle in the response to exercise
      training.

PMID- 26303256
TI  - Effects of controlled diesel exhaust exposure on apoptosis and proliferation
      markers in bronchial epithelium - an in vivo bronchoscopy study on asthmatics,
      rhinitics and healthy subjects.
AB  - BACKGROUND: Epidemiological evidence demonstrates that exposure to traffic
      derived pollution worsens respiratory symptoms in asthmatics, but controlled
      human exposure studies have failed to provide a mechanism for this effect. Here
      we investigated whether diesel exhaust (DE) would induce apoptosis or
      proliferation in the bronchial epithelium in vivo and thus contribute to
      respiratory symptoms. METHODS: Moderate (n = 16) and mild (n = 16) asthmatics,
      atopic non-asthmatic controls (rhinitics) (n = 13) and healthy controls (n = 21)
      were exposed to filtered air or DE (100 MUg/m(3)) for 2 h, on two separate
      occasions. Bronchial biopsies were taken 18 h post-exposure and
      immunohistochemically analysed for pro-apoptotic and anti-apoptotic proteins
      (Bad, Bak, p85 PARP, Fas, Bcl-2) and a marker of proliferation (Ki67). Positive
      staining was assessed within the epithelium using computerized image analysis.
      RESULTS: No evidence of epithelial apoptosis or proliferation was observed in
      healthy, allergic or asthmatic airways following DE challenge. CONCLUSION: In the
      present study, we investigated whether DE exposure would affect markers of
      proliferation and apoptosis in the bronchial epithelium of asthmatics, rhinitics
      and healthy controls, providing a mechanistic basis for the reported increased
      airway sensitivity in asthmatics to air pollutants. In this first in vivo
      exposure investigation, we found no evidence of diesel exhaust-induced effects on
      these processes in the subject groups investigated.

PMID- 26303259
TI  - [Percutaneous needle aponeurotomy for Dupuytren's disease].
AB  - OBJECTIVE: Percutaneous transverse aponeurotomy of the cord by using a hypodermic
      needle as a scalpel blade in order to improve function of the hand. INDICATIONS:
      Symptomatic flexion contracture with positive table top test caused by a single,
      palpable cord within the palm (primarily Tubiana stages I and II).
      CONTRAINDICATIONS: Multiple, infiltrating or broad-based cords within the palm;
      irritated skin conditions; exclusive digital cord localization; recurrence after
      aponeurectomy; previous surgical intervention at the site of interest, digital
      nerve lesions; lack of patient compliance. SURGICAL TECHNIQUE: Pinpoint surface
      anesthesia is obtained by injecting each portal area subdermally with 0.1 ml of
      local anesthetic. These applications start from distally to proximally within the
      palm while the most distal injection site is located proximal to the distal palm
      crease. Then the needle tip is introduced perpendicular to the cord. Sawing
      movements through the cord are performed transversely. While passively extending
      the contracted finger, the cord is held under tension which guarantees safe
      cutting. Patients are encouraged to report immediate pain sensation or numbness
      in order to prevent injuries to neurovascular structures and active finger
      flexion excludes tendon lesions during the procedure. Introducing the needle tip
      may be performed at several sites along the cord, if necessary, from distal to
      proximal at least 5 mm apart with prior pinpoint surface anesthesia. Finally,
      cautious passive stretching may be done after each release. POSTOPERATIVE
      MANAGEMENT: Bandaging allowing immediate motion; application of a hand-based
      extension splint-glove during the night for 3-6 months. RESULTS: Recurrence rate
      was 53% in 15 retrospectively examined patients after a mean interval of 40
      months postoperatively.

PMID- 26303260
TI  - Update on epidemiology of canine babesiosis in Southern France.
AB  - BACKGROUND: Canine babesiosis is an emerging or re-emerging disease caused by
      Babesia and Theileria protozoans, also called piroplasms, transmitted by Ixodid
      ticks. In Europe, four etiological agents have been identified to date, namely
      Babesia canis, B. vogeli, B. gibsoni and Theileria annae. France has a high
      prevalence of canine babesiosis and two tick species, Dermacentor reticulatus and
      Rhipicephalus sanguineus, are supposed to transmit B. canis and B. vogeli
      respectively. In southern France, where dog infections with B. vogeli were
      recently confirmed, no comprehensive study was performed to date on piroplasm
      species infecting dogs. Thus, a large scale survey involving veterinary clinics,
      kennels and tick collection from the environment was conducted from 2010 to 2012
      in this area. RESULTS: From 2010 to 2012, 140 dog blood samples and 667 ticks
      were collected. All blood and a subset of ticks were screened for the presence of
      piroplasms by PCR amplification of 18S rDNA. B. vogeli, B. canis and T. annae
      were detected in 13.6, 12.9 and 0.7 % dogs respectively. B. vogeli and B. canis
      were detected in 10.5 % and in 1.6 % R. sanguineus ticks including 1.3 % co
      infections. B. canis was the only species detected in D. reticulatus ticks (9.7
      %). B. canis infections were only recorded in the southwest of France whereas B.
      vogeli was mainly found in the southeast. Finally, a significantly higher
      prevalence of B. vogeli infection was found in Gard compared to Corsica and Drome
      regions, both in dogs (p < 0.002) and R. sanguineus ticks (p < 0.02) although R.
      sanguineus was the main ticks species removed from dogs in those three areas.
      CONCLUSIONS: The survey confirmed the circulation of both B. canis and B. vogeli
      in dogs in southern France with differences in distribution probably linked to
      the distribution of their respective vectors. It also showed differences in
      prevalence of B. vogeli infection in areas similar in terms of risk of dogs
      infestation with R. sanguineus. Further studies focusing on genetic and
      microbiota of R. sanguineus ticks should be conducted to explore other biological
      interactions that may explain the differences observed.

PMID- 26303261
TI  - Leaf aquaporin transcript abundance in peanut genotypes diverging in expression
      of the limited-transpiration trait when subjected to differing vapor pressure
      deficits and aquaporin inhibitors.
AB  - A plant trait currently being exploited to decrease crop yield loss under water
      deficit conditions is limited-transpiration rate (TRlim ) under high atmospheric
      vapor pressure deficit (VPD) conditions. Although limited genotype comparisons
      for the TRlim trait have been performed in peanut (Arachis hypogaea), no detailed
      study to describe the basis for this trait in peanut has been reported. Since it
      has been hypothesized that the TRlim trait may be a result of low leaf hydraulic
      conductance associated with aquaporins (AQPs), the first objective of this study
      was to examine a possible correlation of TRlim to leaf AQP transcriptional
      profiles in six peanut cultivars. Five of the studied cultivars were selected
      because they expressed TRlim while the cultivar York did not. Transcripts of six
      AQPs were measured. Under exposure to high vapor pressure deficit, cultivar C 76
      16 had decreased AQP transcript abundance for four of the six AQPs but in York
      only one AQP had decreased abundance. The second objective was to explore the
      influence of AQP inhibitors mercury and silver on expression of TRlim and AQP
      transcription profiles. Quantitative RT-PCR data were compared in cultivars York
      and C 76-16, which had the extreme response in TR to VPD. Inhibitor treatment
      resulted in increased abundance of AQP transcripts in both. The results of these
      experiments indicate that AQP transcript abundance itself may not be useful in
      identifying genotypes expressing the TRlim trait under high VPD conditions. 

PMID- 26303262
TI  - Foreword to Pediatric Travel Medicine.

PMID- 26303265
TI  - Professional quality of life: A cross-sectional survey among Chinese clinical
      nurses.
AB  - The Professional Quality of Life Scale was adapted to create a Chinese version to
      investigate the professional quality of life of Chinese nurses and possible risk
      factors. A cross-sectional survey was conducted among 752 nurses sampled from
      four general hospitals in Shanghai, China. An expert panel, cognitive review, and
      pretest were used to ensure cultural adaptability. Psychometric tests included
      reliability and validity. One-way and multivariate analysis of variance were
      conducted for statistical analysis. Content validity indexes of all items were
      over 0.90. Five items were excluded because their item-total correlations and
      factor loading of exploratory factor analysis were less than 0.3. The 25-item
      scale revealed acceptable reliability. Confirmatory factor analysis supported its
      structure. There was variation in the scores between different departments,
      religions, working positions, nursing experiences, forms of employment, and
      average working hours (all P < 0.05). This study extended the application of the
      original scale in Chinese nursing culture. Attention should be paid to risk
      factors and differences between East and West. 

PMID- 26303263
TI  - Fast Technology Analysis Enables Identification of Species and Genotypes of
      Latent Microsporidia Infections in Healthy Native Cameroonians.
AB  - Several enteric microsporidia species have been detected in humans and other
      vertebrates and their identifications at the genotype level are currently being
      elucidated. As advanced methods, reagents, and disposal kits for detecting and
      identifying pathogens become commercially available, it is important to test them
      in settings other than in laboratories with "state-of-the-art" equipment and well
      trained staff members. In the present study, we sought to detect microsporidia
      DNA preserved and extracted from FTA (fast technology analysis) cards spotted
      with human fecal suspensions obtained from Cameroonian volunteers living in the
      capital city of Yaounde to preclude the need for employing spore-concentrating
      protocols. Further, we tested whether amplicon nucleotide sequencing approaches
      could be used on small aliquots taken from the cards to elucidate the diversity
      of microsporidia species and strains infecting native residents. Of 196 samples
      analyzed, 12 (6.1%) were positive for microsporidia DNA; Enterocytozoon bieneusi
      (Type IV and KIN-1), Encephalitozoon cuniculi, and Encephalitozoon intestinalis
      were identified. These data demonstrate the utility of the FTA cards in
      identifying genotypes of microsporidia DNA in human fecal samples that may be
      applied to field testing for prevalence studies. 

PMID- 26303266
TI  - YouTube as a source of useful information on diabetes foot care.
AB  - Diabetes foot care related videos were identified in YouTube to assess their
      usefulness as a source of information. Two physician reviewers evaluated the
      videos and categorized those as very-useful (11.2%), moderately-useful (14.6%),
      somewhat-useful (24.7%) and not-useful (49.4%). YouTube videos on diabetes foot
      care contained a variety of content ranging from very useful to not useful. 

PMID- 26303264
TI  - The glucagon-like peptide 1 receptor agonist liraglutide attenuates the
      reinforcing properties of alcohol in rodents.
AB  - The incretin hormone, glucagon-like peptide 1 (GLP-1), regulates gastric
      emptying, glucose-dependent stimulation of insulin secretion and glucagon
      release, and GLP-1 analogs are therefore approved for treatment of type II
      diabetes. GLP-1 receptors are expressed in reward-related areas such as the
      ventral tegmental area and nucleus accumbens, and GLP-1 was recently shown to
      regulate several alcohol-mediated behaviors as well as amphetamine-induced,
      cocaine-induced and nicotine-induced reward. The present series of experiments
      were undertaken to investigate the effect of the GLP-1 receptor agonist,
      liraglutide, on several alcohol-related behaviors in rats that model different
      aspects of alcohol use disorder in humans. Acute liraglutide treatment suppressed
      the well-documented effects of alcohol on the mesolimbic dopamine system, namely
      alcohol-induced accumbal dopamine release and conditioned place preference in
      mice. In addition, acute administration of liraglutide prevented the alcohol
      deprivation effect and reduced alcohol intake in outbred rats, while repeated
      treatment of liraglutide decreased alcohol intake in outbred rats as well as
      reduced operant self-administration of alcohol in selectively bred Sardinian
      alcohol-preferring rats. Collectively, these data suggest that GLP-1 receptor
      agonists could be tested for treatment of alcohol dependence in humans. 

PMID- 26303267
TI  - Preoperative Cardiac Assessment before Carotid Surgery: Should Perhaps Things
      Change?
AB  - Carotid endarterectomy has been associated with perioperative symptomatic or
      asymptomatic myocardial ischemia and cardiac mortality although it has been
      classified as a procedure of intermediate cardiac risk. Recent data indicate that
      the Cardiac Risk Index score for preoperative assessment by the latest guidelines
      is not suitable for vascular surgery procedures in general and carotid procedures
      in particular. This review aims to present and analyze all these results,
      concluding that current recommendations for this specific procedure should
      perhaps be reevaluated. 

PMID- 26303268
TI  - Complex Iatrogenic Dissection Complicating Thoracic Endovascular Aneurysm Repair.
AB  - BACKGROUND: To report one the most feared complication of thoracic endovascular
      aneurysm repair (TEVAR); a retrograde aortic dissection who can involve the
      aortic arch or ascending aorta, which require commonly coextensive open surgical
      repair. CASE REPORTS: We report 2 cases of combined retrograde and antegrade
      dissection after endovascular treatment of an aneurysm of the descending aorta.
      In both cases, a dissection was identified at short-term follow-up; which
      required open surgical repair in one case and an additional endovascular
      treatment for the second case. CONCLUSIONS: The incidence of extensive iatrogenic
      dissection after TEVAR is relatively low, open repair should be considered as a
      primary option in some cases with limited aortic dilatation to avoid such life
      threatening complications.

PMID- 26303269
TI  - Predictive Factors for Type II Endoleaks after Treatment of Abdominal Aortic
      Aneurysm by Conventional Endovascular Aneurysm Repair.
AB  - BACKGROUND: The aim of this study was to identify the predictive factors for the
      development of type II endoleaks (EL-II) after endovascular aneurysm repair
      (EVAR). METHODS: We assessed the preoperative and postoperative computed
      tomography data of 308 patients who underwent EVAR between 2000 and 2012 and in
      84 of whom primary or secondary EL-II occurred. The data analyzed were:
      demographics, number and diameter of lumbar arteries (LAs), inferior mesenteric
      artery (IMA), median sacral artery (MSA), accessory renal arteries (ARas),
      maximum diameter of infrarenal abdominal aortic aneurysm, diameter and length of
      proximal aortic neck. Statistical analysis was performed using Stata software
      (version 12). Categorical parameters were compared between groups using chi
      squared or Fisher's exact tests as appropriate. Continuous variables were
      analyzed using Student's t-test or Mann-Whitney test as appropriate (normality
      studied by the Shapiro-Wilk and homoscedasticity verified using the Fisher
      Snedecor test). RESULTS: Of the 308 patients included (mean age, 73.8 +/- 8.74
      years), 284 (92%) were men, 61 (20%) were smokers, 113 (37%) had chronic
      obstructive pulmonary disease, 215 (70%) were taking antiplatelet. Respectively,
      13, 51, 60, 103, 28, 40, 2, and 7 patients had 1, 2, 3, 4, 5, 6, 7, and 8 patent
      LAs. Before surgery, 221 IMAs and 136 MSA were patent. The sources of EL-II were:
      LA (n = 51), IMA (n = 22), MSA (n = 1), IMA and LA (n = 8), IMA and ARa (n = 1),
      and unknown (n = 1). Logistic regression models adjusting for clinically relevant
      covariables (age, American Society of Anesthesiologists, smoking status,
      dyslipidemia, and diuretics) were proposed to study morphologic EL-II predictive
      factors, first in the entire population, and then in the more specific population
      for whom IMA was patent. Risk factors of occurrence EL-II were: permeability of
      the IMA (70 patients [83%] vs. 155 [69%], P = 0.01), IMA diameter (3.49 mm vs.
      2.71 mm, P < 0.001), number of LAs patent higher than or equal to 4 (P < 0.001),
      the mean LA diameter greater than 2.4 mm (P < 0.001), and MSA diameter (2.28 mm
      vs. 1.94 mm; P < 0.01). CONCLUSIONS: Our results show the major role of the
      number and diameter of the patent aortic branches in the development of EL-II. As
      they can result in complications increasing the morbidity and mortality after
      EVAR, it is relevant to identify the risk factors of their occurrence.

PMID- 26303270
TI  - Carotid Endarterectomy in the Face of a Persistent Hypoglossal Artery.
AB  - A 68-year-old woman presented with signs and symptoms suggestive of a
      cerebrovascular accident. Her work-up revealed left internal carotid artery
      stenosis consistent with her presentation of a left middle cerebral artery
      distribution stroke. Imaging also incidentally revealed a persistent hypoglossal
      artery. She underwent carotid endarterectomy. Our intraoperative strategy for
      management of this persistent fetal anomaly is reviewed. 

PMID- 26303271
TI  - Aortogastric Fistula Due to a Penetrating Atherosclerotic Aortic Ulcer.
AB  - Penetrating aortic ulcer (PAU) is an atherosclerotic lesion with ulceration that
      penetrates the internal elastic lamina of the aortic wall. PAUs are classified as
      a category of acute aortic syndrome and have a reported rupture rate of up to
      38%. To our knowledge, there is no prior published report of a PAU causing an
      aortogastric fistula. With the goal of raising awareness of this potentially
      catastrophic complication, we present herein a case of a PAU that ruptured into
      the gastric fundus, resulting in massive bleeding. The diagnosis was confirmed by
      computed tomography angiography, and thoracic endovascular aortic repair was used
      to control bleeding. Unfortunately, the patient did not survive the severe
      hypovolemic shock. 

PMID- 26303272
TI  - Iliac Artery-Uretero-Colonic Fistula Presenting as Severe Gastrointestinal
      Hemorrhage and Hematuria: A Case Report and Review of the Literature.
AB  - Arterioenteric fistulas represent an infrequent but potentially fatal cause of
      gastrointestinal hemorrhage. Patients often present in extremis from shock and
      sepsis. This mandates a rapid diagnosis so that prompt, potentially life-saving
      interventions can be performed. We report the case of a 35-year-old man who
      presented with hematuria and hematochezia secondary to an iliac artery-uretero
      colonic fistula that developed years after open common iliac artery aneurysm
      repair. His condition rapidly progressed to hemorrhagic shock, and he underwent
      successful endovascular treatment with a covered stent graft as a bridge to
      definitive open surgery. Subsequently, graft explantation, extra-anatomic
      arterial bypass, bowel resection, and ureter ligation was undertaken. A summary
      of the literature on iliac artery-enteric fistulas follows. 

PMID- 26303273
TI  - Implication of Akt, ERK1/2 and alternative p38MAPK signalling pathways in human
      colon cancer cell apoptosis induced by green tea EGCG.
AB  - We investigated apoptosis induced by the green tea component the epigallocatechin
      3-gallate (EGCG) and the pathways underlying its activity in a colon cancer cell
      line. A complete understanding of the mechanism(s) and molecules targeted by
      green tea polyphenols could be useful in developing novel therapeutic approaches
      for cancer treatment. EGCG, which is the major polyphenol in green tea, has
      cytotoxic effects and induced cell death in HT-29 cell death. In this study, we
      evaluated the effect EGCG on mitogen-activated protein kinase (MAPK) and Akt
      pathways. EGCG treatment increased phospho-ERK1/2, -JNK1/2 and -p38alpha, 
      p38gamma and -p38delta, as well as phospho-Akt levels. Using a combination of
      kinase inhibitors, we found that EGCG-induced cell death is partially blocked by
      inhibiting Akt, ERK1/2 or alternative p38MAPK activity. Our data suggest that
      these kinase pathways are involved in the anti-cancer effects of EGCG and
      indicate potential use of this compound as chemotherapeutic agent for colon
      cancer treatment. 

PMID- 26303274
TI  - Postoperative hyperglycemia after 4- vs 8-10-mg dexamethasone for postoperative
      nausea and vomiting prophylaxis in patients with type II diabetes mellitus: a
      retrospective database analysis.
AB  - STUDY OBJECTIVE: The study objective is to compare change in postoperative blood
      glucose from preoperative values in patients with type II diabetes mellitus
      receiving 4- or 8-10-mg dexamethasone for postoperative nausea and vomiting
      prophylaxis. DESIGN: This is a retrospective database study. SETTING: The setting
      is at an academic university medical center. PATIENTS: There are 1037 adult
      patients, American Society of Anesthesiologists physical status I-IV, with type
      II diabetes mellitus, undergoing elective surgery between January 1, 2006, and
      March 31, 2012, and who were hospitalized for at least 24 hours. INTERVENTIONS:
      The interventions are dexamethasone 4 or 8-10 mg for postoperative nausea and
      vomiting prophylaxis. MEASUREMENTS: Age, sex, American Society of
      Anesthesiologists class, height, weight, body mass index, surgery date, type and
      duration of surgery, hemoglobin A1c (HbA1c) within 180 days of surgery, type of
      anesthesia, preoperative blood glucose in the preoperative holding area, maximum
      blood glucose in the postanesthesia care unit (PACU) and first 24 hours
      postoperatively, and insulin requirements intraoperatively and in PACU. MAIN
      RESULTS: In unadjusted analysis, the 8-10-mg dose was associated with greater
      (mean +/- SD) increase in blood glucose compared with the 4-mg dose in PACU (58
      +/- 50 vs 43 +/- 45 mg/dL, P < .0001) and over 24 hours (101 +/- 71 vs 67 +/- 65
      mg/dL, P < .0001). In the multivariable model, predictors of blood glucose
      increase in PACU included dexamethasone dose (P < .0001), preoperative serum
      glucose (P < .0001), duration of surgery (P < .0001), and total dose of insulin
      (P < .0001). Over 24 hours, the significant predictors of glucose increase
      included dexamethasone dose (P < .0001), preoperative blood glucose level (P <
      .0001), duration of surgery (P < .0001), year of surgery (P = .04), and
      neurosurgical procedures (P = .02). This model estimates the increase in
      postoperative glucose to be 25 mg/dL higher over 24 hours with dexamethasone 8-10
      mg than with 4 mg (95% confidence limits, 18-32 mg/dL). CONCLUSIONS:
      Dexamethasone 8-10 mg is associated with a significantly greater perioperative
      increase in blood glucose compared with a 4-mg dose.

PMID- 26303275
TI  - Explaining risk for suicidal ideation in adolescent offspring of mothers with
      depression.
AB  - BACKGROUND: It is well-established that offspring of depressed mothers are at
      increased risk for suicidal ideation. However, pathways involved in the
      transmission of risk for suicidal ideation from depressed mothers to offspring
      are poorly understood. The aim of this study was to examine the contribution of
      potential mediators of this association, including maternal suicide attempt,
      offspring psychiatric disorder and the parent-child relationship. METHOD: Data
      were utilized from a population-based birth cohort (ALSPAC). Three distinct
      classes of maternal depression symptoms across the first 11 years of the child's
      life had already been identified (minimal, moderate, chronic-severe). Offspring
      suicidal ideation was assessed at age 16 years. Data were analysed using
      structural equation modelling. RESULTS: There was evidence for increased risk of
      suicidal ideation in offspring of mothers with chronic-severe depression symptoms
      compared to offspring of mothers with minimal symptoms (odds ratio 3.04, 95%
      confidence interval 2.19-4.21). The majority of this association was explained
      through maternal suicide attempt and offspring psychiatric disorder. There was
      also evidence for an independent indirect effect via the parent-child
      relationship in middle childhood. There was no longer evidence of a direct effect
      of maternal depression on offspring suicidal ideation after accounting for all
      three mediators. The pattern of results was similar when examining mechanisms for
      maternal moderate depression symptoms. CONCLUSIONS: Findings highlight that
      suicide prevention efforts in offspring of depressed mothers should be
      particularly targeted at both offspring with a psychiatric disorder and offspring
      whose mothers have made a suicide attempt. Interventions aimed at improving the
      parent-child relationship may also be beneficial.

PMID- 26303276
TI  - Analysis of lipid and fatty acid composition of three species of scorpions with
      relation to different organs.
AB  - Within arthropods most of the information related to the type of mobilization and
      storage of lipids is found in insects and crustaceans. Literature is scarce with
      relation to scorpions. This order is a remarkably important model of the
      biochemistry, since it is characterized as an animal with very primitive traits
      which have varied minimally through time. In the present study we characterize
      and compare lipids and fatty acids present in three species of scorpion:
      Timogenes elegans, Timogenes dorbignyi, and Brachistosternus ferrugineus,
      focusing the study on the main organs/tissues involved in the dynamics of lipids.
      As found in the fat body of insects, hepatopancreas of crustaceans and midgut
      diverticula of spiders, the hepatopancreas of the three species studied here
      turned out to be the organ of lipid storage (great quantity of
      triacylglycerides). With relation to the hemolymph and muscles, a great quantity
      of phospholipids was observed, which is possibly involved in membrane formation.
      It is important to highlight that unlike what happens in insects, in scorpions
      the main circulating energetic lipid is the triacylglyceride. This lipid is found
      in greater proportion in the hepatopancreas of females, surely for reproduction.
      The fatty acid of the different organs/tissues analyzed remained constant in the
      three species studied with certain characteristic patterns, thus observing
      saturated and unsaturated most abundant fatty acids of C16 and C18. Finally, it
      could be observed that in T. elegans, T. dorbignyi and B. ferrugineus scorpions,
      there is a lack of 20:4 that generates a special condition within fatty acids of
      arthropods. 

PMID- 26303277
TI  - Emotional caricatures in frontotemporal dementia.

PMID- 26303278
TI  - Why it is pointless to ask under which specific circumstances the bilingual
      advantage occurs.

PMID- 26303279
TI  - Gastrointestinal Lymphoma in Southwest China: Subtype Distribution of 1,010 Cases
      Using the WHO (2008) Classification in a Single Institution.
AB  - The gastrointestinal tract (GIT) is the most common anatomic site of extranodal
      non-Hodgkin lymphoma (NHL) involvement. The classification criteria of lymphoma
      have changed in recent decades, and few large-sample studies regarding subtype
      analysis of lymphoma have been performed in this site. AIM: Therefore, the
      present study was conducted to analyze the histological subtype distribution of
      the GIT. METHOD: All patients in a single institution with a diagnosis of primary
      NHL in the GIT were enrolled between January 2007 and April 2014. The patients
      were categorized according to the WHO (2008) classification of tumors of
      hematopoietic and lymphoid tissue. RESULT: A total of 1,010 eligible cases
      diagnosed as NHL were collected in this study. The male:female ratio was 1.7:1
      and the median age was 55 years. The percent of patients with lymphoma
      involvement in the stomach was 52% (n = 522), and the remaining 48% (n = 484) had
      intestinal tract involvement. Histologically, diffuse large B cell lymphoma
      (DLBCL) was the most common subtype in all of the GIT lymphoma cases, and was
      also the most common subtype in cases involving the stomach (78%) and the
      intestinal tract (53%). The incidence of DLBCL and mucosa-associated lymphoid
      tissue lymphoma in the stomach was significantly higher than the incident in the
      intestinal tract (p < 0.01). T and NK cell lymphoma was significantly more common
      in the intestinal tract than in the stomach (p < 0.01). Extranodal NK/T cell
      lymphoma nasal type (ENKTL-N) was the most common subtype of T and NK cell
      lineage lymphoma in GIT and was also the second most common intestinal tract
      involved lymphoma. CONCLUSION: DLBCL was the most frequent lymphoma in the
      stomach and in the intestinal tract. T and NK cell lineage lymphoma had a higher
      occurrence in the intestinal tract than in the stomach. ENKTL-N was the most
      frequent subtype of lymphoma derived from NK/T cell lineage, and was the second
      most common lymphoma among all intestinal tract lymphomas.

PMID- 26303280
TI  - Cephalomedullary nails: factors associated with impingement of the anterior
      cortex of the femur in a Hispanic population.
AB  - INTRODUCTION: Impingement and penetration of the anterior cortex of the femur
      have been reported as complications after cephalomedullary nailing. The purpose
      of this study was to determine factors related to nail impingement in our
      population of Hispanic patients. MATERIALS AND METHODS: A non-matched case
      control study was carried out and 156 patients who underwent cephalomedullary
      nailing from 2010 and 2013 were included; 78 cases with anterior cortical
      impingement and 78 control cases without impingement were documented. Demographic
      variables and specifications of the nails such as manufacture and radius of
      curvature were recorded. The presence of impingement, angle of incidence on
      radiographs--indirect measurement of the femoral bow on the sagittal plane--and
      nail entry site were determined. Bivariate and multivariate logistic regression
      analyses were performed to identify the factors associated with cortical
      impingement. RESULTS: The distribution by sex corresponded to 87 females (56%)
      and 69 males (44%) with a mean age of 75 years [SD 18.2]. Cortical impingement
      was presented in 78 cases (50%) and 6 (3.8%) patients evidenced penetration of
      the anterior cortex of the femur. On the bivariate analysis the posterior nail
      start site is highlighted, which showed a positive association with impingement
      (OR 4.3; 95% CI 1.1-36 and p = 0.04). After the multivariate analysis, the
      factors associated with anterior cortical impingement included female gender (OR
      2.2; 95 % CI 1.1-4.6 and p <= 0.038), straight nails-short nails-(OR 4.9; 95% CI
      2.2-10 and p <= 0.001) and angle of incidence >=7 degrees  (OR 4.9; 95% CI 2.2-10
      and p <= 0.001), the latter showing a likelihood of 57 % for impingement,
      increasing to 90% with an angle of incidence of 11 degrees . CONCLUSIONS:
      Posterior entry site should be avoided and an anterior site should be used.
      Female gender, straight nails and greater angle of incidence of the femur were
      associated with cortical impingement. A specific intramedullary nail design is
      needed for the Hispanic population due to high impingement and anterior cortical
      penetration rates seen with conventional nails. Short curved nails and long nails
      with a lower radius of curvature are required.

PMID- 26303281
TI  - Navigation-assisted versus conventional total knee replacement: no difference in
      patient-reported outcome measures (PROMs) at 1 and 2 years.
AB  - INTRODUCTION: Navigation technique for total knee replacement has been shown to
      improve accuracy of prosthesis alignment in several studies. The purpose was to
      compare the patient-reported outcome measures in primary total knee replacement
      (TKR) using navigation versus conventional surgical technique at 1- and 2-year
      follow-up. MATERIALS AND METHODS: A retrospective review of prospectively
      collected patient-reported outcome data for 351 consecutively performed primary
      TKR was included in the study. The study group (N = 113) included patients who
      had Triathlon TKR using articular surface mounted (ASM Stryker) navigation
      technique and control group (N = 238) included patients who had Triathlon TKR
      using conventional jig. In addition to the WOMAC (Western Ontario and McMaster
      University Osteoarthritis Index) and SF-36 (Medical Outcomes Trust Short Form
      36), a short self-report questionnaire evaluating the level of satisfaction,
      quality of life and whether patients would undergo knee replacement again.
      RESULTS: WOMAC: no significant difference between the groups was noted in mean
      WOMAC pain, function and stiffness scores at 1- and 2-year follow-up. SF-36: no
      significant difference between the groups was seen except in the physical
      function component of score at 1 year (p = 0.019). Navigation group mean 56.78
      (CI 51.06-62.5) versus conventional group mean 48.34 (44.68-52.01) but this
      difference was not observed at 2-year follow-up. CONCLUSIONS: The overall patient
      reported outcome scores improved after total knee replacement but appear to be
      comparable in both groups at 1- and 2-year follow-up.

PMID- 26303282
TI  - Sphingobacterium rhinocerotis sp. nov., isolated from the faeces of Rhinoceros
      unicornis.
AB  - A novel Gram-negative, strictly aerobic, short rod-shaped, non-motile bacterium,
      designated YIM 101302(T), was isolated from the faeces of Rhinoceros unicornis
      dwelling in the Yunnan Wild Animal Park, Yunnan province, South-West China. The
      16S rRNA gene sequence analysis revealed a clear affiliation of strain YIM
      101302(T) to the genus Sphingobacterium. The newly isolated bacterium was found
      to be closely related to Sphingobacterium composti T5-12(T) (97.1% 16S rRNA
      sequence identity) and Sphingobacterium alimentarium WCC 4521(T) (95.6% 16S rRNA
      sequence identity) forming a distinct clade with these two species. Polar lipids
      of strain YIM 101302(T) were identified as phosphatidylethanolamine,
      phosphatidylmethylethanolamine, phosphatidylglycerol, phosphatidylinositol, an
      unidentified aminophospholipid, and three unidentified polar lipids; the
      predominant menaquinone as MK-7 and the major fatty as iso-C15:0. The genomic DNA
      G+C content was determined to be 38.9 mol%. The DNA-DNA hybridization values
      between strain YIM 101302(T) and S. composti T5-12(T), was 53.6 +/- 5.8%. These
      results indicates that strain YIM 101302(T) represents a novel species of the
      genus Sphingobacterium, for which the name Sphingobacterium rhinocerotis sp. nov.
      is proposed. The type strain is YIM 101302(T) (=CCTCC AB 2013218(T) = KCTC
      42533(T)).

PMID- 26303283
TI  - Oceanobacillus bengalensis sp. nov., a bacterium isolated from seawater of the
      Bay of Bengal.
AB  - A Gram-stain positive, motile, and subterminal endospore-forming rod-shaped
      bacterium, designated strain Ma-21(T), was isolated from seawater of the Bay of
      Bengal. Strain Ma-21(T) was found to grow optimally at 37  degrees C and pH 8.0
      with 3% (w/v) NaCl. Phylogenetic analyses showed that strain Ma-21(T) forms a
      distinct phylogenetic lineage close to Oceanobacillus chungangensis CAU 1051(T),
      Oceanobacillus caeni S-11(T), Oceanobacillus arenosus CAU 1183(T), Oceanobacillus
      halophilum GD01(T) and Ornithinibacillus heyuanensis GIESS003(T) in the family
      Bacillaceae. The cell wall of strain Ma-21(T) was found to contain meso
      diaminopimelic acid as the diagnostic diamino acid, which is in line with those
      of members of the genus Oceanobacillus. The genomic DNA G+C content was
      determined to be 35.9 mol%. The only respiratory quinone detected was MK-7. The
      major cellular fatty acids were identified as anteiso-C(15:0) and anteiso
      C(17:0). The major polar lipids were found to be diphosphatidylglycerol and
      phosphatidylglycerol. On the basis of phylogenetic, chemotaxonomic and phenotypic
      properties, strain Ma-21(T) is suggested to represent a novel species in the
      genus Oceanobacillus, for which the name Oceanobacillus bengalensis sp. nov. is
      proposed. The type strain is Ma-21(T) (=CGMCC 1.12799(T) = KCTC 33416(T) = MCCC
      1K00260(T)).

PMID- 26303284
TI  - TMSBr/InBr3-promoted Prins cyclization/homobromination of dienyl alcohol with
      aldehyde to construct cis-THP containing an exocyclic E-alkene.
AB  - A TMSBr/InBr3-promoted Prins cyclization/homobromination reaction of dienyl
      alcohol with aldehyde has been developed to construct a unique cis-E THP shown as
      the A ring in (-)-exiguolide and the B ring in bryostatins. 

PMID- 26303285
TI  - Abuse of New Psychoactive Substances: Threats and Solutions.

PMID- 26303286
TI  - Single phase Si1-xGex nanocrystals and the shifting of the E1 direct energy
      transition.
AB  - We report preparation and characterization of Si1-xGex alloys with varied
      composition x of a large range from 0-1. The materials have been obtained by co
      sputtering, followed by a heat treatment process at 600, 800, and 1000  degrees C
      for 30 min in a nitrogen gas atmosphere. X-ray diffraction data have revealed the
      formation of single-phase nanoparticles in the face-centered cubic (FCC)
      structure of Si1-xGex alloys. We found that lattice constant a of the Si1-xGex
      alloys increased linearly with the composition parameter x. Average diameters of
      the single-phase nanoparticles were estimated to be between 3-10 nm. Further
      evidence of FCC single-phase [Formula: see text] nanoparticles has been obtained
      by high resolution transmission electron microscopy. From absorption spectra, the
      gradual shift of the direct phononless transition identified for the E1 point in
      the Brillouin zone of bulk Ge is observed in single-phase Si1-xGex nanoparticles
      as a function of the composition parameter x. 

PMID- 26303287
TI  - The in vivo role of DMP-1 and serum phosphate on bone mineral composition.
AB  - Human DMP1 mutations or Dmp1-null (KO) mice display hypophosphatemia rickets,
      suggesting a causative role of low phosphate (P) in development of osteomalacia.
      To address the direct contribution of P to the in vivo bone mineralization we
      analyzed the properties of femurs obtained from Dmp1 null mice and wild type (WT)
      mice under a normal or high phosphorous (HiP) diet using combined assays,
      including histological examination, micro computed tomography (MUCT), X-ray
      absorption near edge structure (XANES) spectroscopy and Raman spectroscopy.
      Histology and XANES indicate that WT mice have phosphate coordinated with Ca in
      the form of hydroxyapatite and tricalcium phosphate, while the KO mice have
      poorly coordinated soluble phosphates in their structure in both the normal and
      HiP diets. Raman spectroscopy and XANES indicate a higher carbonate/phosphate
      ratio and a low mineral/matrix ratio in the osteoid clusters in the KO femurs,
      which was only partially improved by HiP diets. Thus, we conclude that the
      hypophosphatemia induced osteomalacia phenotype in Dmp1 KO mice is contributed by
      at least two factors: the low Pi level and the DMP1 local function in
      mineralization. 

PMID- 26303288
TI  - In vivo monitoring of bone architecture and remodeling after implant insertion:
      The different responses of cortical and trabecular bone.
AB  - The mechanical integrity of the bone-implant system is maintained by the process
      of bone remodeling. Specifically, the interplay between bone resorption and bone
      formation is of paramount importance to fully understand the net changes in bone
      structure occurring in the peri-implant bone, which are eventually responsible
      for the mechanical stability of the bone-implant system. Using time-lapsed in
      vivo micro-computed tomography combined with new composite material implants, we
      were able to characterize the spatio-temporal changes of bone architecture and
      bone remodeling following implantation in living mice. After insertion, implant
      stability was attained by a quick and substantial thickening of the cortical
      shell which counteracted the observed loss of trabecular bone, probably due to
      the disruption of the trabecular network. Within the trabecular compartment, the
      rate of bone formation close to the implant was transiently higher than far from
      the implant mainly due to an increased mineral apposition rate which indicated a
      higher osteoblastic activity. Conversely, in cortical bone, the higher rate of
      bone formation close to the implant compared to far away was mostly related to
      the recruitment of new osteoblasts as indicated by a prevailing mineralizing
      surface. The behavior of bone resorption also showed dissimilarities between
      trabecular and cortical bone. In the former, the rate of bone resorption was
      higher in the peri-implant region and remained elevated during the entire
      monitoring period. In the latter, bone resorption rate had a bigger value away
      from the implant and decreased with time. Our approach may help to tune the
      development of smart implants that can attain a better long-term stability by a
      local and targeted manipulation of the remodeling process within the cortical and
      the trabecular compartments and, particularly, in bone of poor health. 

PMID- 26303289
TI  - Ethnic differences in the degree of morning blood pressure surge and in its
      determinants between Japanese and European hypertensive subjects: data from the
      ARTEMIS study.
AB  - Morning blood pressure (BP) surge has been reported to be a prognostic factor for
      cardiovascular events. Its determinants are still poorly defined, however. In
      particular, it is not clear whether ethnic differences play a role in determining
      morning surge (MS) size. Aim of our study was to explore whether differences
      exist in the size of MS between Japanese and Western European hypertensive
      patients. We included 2887 untreated hypertensive patients (age 62.3+/-8.8 years)
      from a European ambulatory BP monitoring database and 811 hypertensive patients
      from a Japanese database (Jichi Medical School Ambulatory Blood Pressure
      Monitoring WAVE1, age 72.3+/-9.8 years) following the same inclusion criteria.
      Their 24-hour ambulatory BP monitoring recordings were analyzed focusing on MS.
      Sleep-trough MS was defined as the difference between mean systolic BP during the
      2 hours after awakening and mean systolic BP during the 1-hour night period that
      included the lowest sleep BP level. The sleep-trough MS was higher in Japanese
      than in European hypertensive patients after adjusting for age and 24-hour mean
      BP levels (40.1 [95% confidence interval 39.0-41.2] versus 23.0 [22.4-23.5] mm
      Hg; P<0.001). This difference remained significant after accounting for
      differences in night-time BP dipping. Age was independently associated with MS in
      the Japanese database, but not in the European subjects. Our results for the
      first time show the occurrence of substantial ethnic differences in the degree of
      MS. These findings may help in understanding the role of ethnic factors in
      cardiovascular risk assessment and in identifying possible ethnicity-related
      differences in the most effective measures to be implemented for prevention of BP
      related cardiovascular events. 

PMID- 26303290
TI  - New potassium binders for the treatment of hyperkalemia: current data and
      opportunities for the future.

PMID- 26303291
TI  - Inhibition of kinin B1 receptors attenuates pulmonary hypertension and vascular
      remodeling.
AB  - This study examined whether the kinin B1 receptor is involved in the pathogenesis
      of pulmonary hypertension, and whether its inhibition could reduce inflammation,
      pulmonary hypertension, vascular remodeling, and right heart dysfunction. Male
      Wistar rats underwent left pneumonectomy. Seven days later, the rats were
      injected subcutaneously with monocrotaline (60 mg/kg). The rats were then
      randomly assigned to receive treatment with vehicle or with BI113823 (a selective
      B1 receptor antagonist, 30 mg/kg, twice per day) via oral gavage from the day of
      monocrotaline injection to day 28. By day 28, BI113823-treated rats had
      significantly lower mean pulmonary artery pressure, less right ventricular
      hypertrophy, and pulmonary arterial neointimal formation than that of the vehicle
      treated rats. Real-time polymerase chain reaction revealed that there was a
      significant increase in mRNA expression of B1 receptors in the lungs of
      monocrotaline-challenged pneumonectomized rats. Treatment with BI113823
      significantly reduced macrophage recruitment, as measured via bronchoalveolar
      lavage. It also markedly reduced CD-68 positive macrophages and proliferating
      cell nuclear antigen positive cells in the perivascular areas, reduced expression
      of inducible nitric oxide synthase, matrix metalloproteinase 2 and 9, and B1
      receptors compared with measurements in vehicle-treated rats. These findings
      demonstrate that kinin B1 receptors represent a novel therapeutic target for
      pulmonary arterial hypertension. 

PMID- 26303292
TI  - Deficiency of angiotensinogen in hepatocytes markedly decreases blood pressure in
      lean and obese male mice.
AB  - We recently demonstrated that adipocyte deficiency of angiotensinogen (AGT)
      ablated high-fat diet-induced elevations in plasma angiotensin II (Ang II)
      concentrations and obesity-hypertension in male mice. Hepatocytes are the
      predominant source of systemic AGT. Therefore, in this study, we defined the
      contribution of hepatocyte-derived AGT to obesity-induced elevations in plasma
      AGT concentrations and hypertension. Male Agt(fl/fl) mice expressing albumin
      driven Cre recombinase were bred to female Agt(fl/fl) mice to generate Agt(fl/fl)
      or hepatocyte AGT-deficient male mice (Agt(Alb)). Mice were fed a low-fat or high
      fat diet for 16 weeks. Hepatocyte AGT deficiency had no significant effect on
      body weight. Plasma AGT concentrations were increased in obese Agt(fl/fl) mice.
      Hepatocyte AGT deficiency markedly reduced plasma AGT and Ang II concentrations
      in lean and obese mice. Moreover, hepatocyte AGT deficiency reduced the content
      and release of AGT from adipose explants. Systolic blood pressure was markedly
      decreased in lean (by 18 mm Hg) and obese Agt(Alb) mice (by 54 mm Hg) compared
      with Agt(fl/fl) controls. To define mechanisms, we quantified effects of Ang II
      on mRNA abundance of megalin, an AGT uptake transporter, in 3T3-L1 adipocytes.
      Ang II stimulated adipocyte megalin mRNA abundance and decreased media AGT
      concentrations. These results demonstrate that hepatocytes are the predominant
      source of systemic AGT in both lean and obese mice. Moreover, reductions in
      plasma angiotensin concentrations in obese hepatocyte AGT-deficient mice may have
      limited megalin-dependent uptake of AGT into adipocytes for the production of Ang
      II in the development of obesity-hypertension. 

PMID- 26303293
TI  - Good's syndrome with opportunistic infection of the central nervous system: a
      case report.
AB  - BACKGROUND: Immunodeficiency with a thymoma (Good's syndrome) is a rare condition
      occurring in patients with adult-onset hypogammaglobulinemia that is progressive
      after the removal of thymoma. Recently, we encountered a patient with Good's
      syndrome who suddenly developed opportunistic encephalitis 4 years after the
      resection of thymoma without a history of infectious complications. CASE
      PRESENTATION: A 58-year-old man, who underwent surgery to remove a thymoma at the
      age of 54, was admitted because of speech difficulties. A brain MRI showed
      multiple lesions involving the frontal lobes, but the CSF finding was normal.
      Acyclovir was empirically administered, and fever as well as his neurological
      symptoms fully recovered within a few days. However, 1 week after admission,
      motor aphasia and mild right hemiparesis reappeared. MRI showed that the lesion
      involving the left cingulate gyrus expanded in size, and revealed an abnormal
      signal intensity lesion in the left corona radiata. Laboratory examination found
      increased CMV pp65 antigen-positive lymphocytes in serum. Antiviral therapy using
      ganciclovir and immunoglobulin replacement therapy was started. The patient has
      since been free from any neurological symptoms for 1 year, and lesions
      demonstrated by MRI are gradually improving. CONCLUSION: Early recognition of
      this rare condition and prompt initiation of therapy are crucially important.
      Awareness of immunodeficiency in a patient after removal of thymoma may help
      neurologists to consider the possibility that opportunistic infection may be the
      cause of cerebral lesions.

PMID- 26303295
TI  - Influence of Delipation on the Energy Metabolism in Pig Parthenogenetically
      Activated Embryos.
AB  - This study was designed not only to measure the effect of delipation on the
      developmental viability of pig parthenogenetically activated (PA) embryos, but
      also to evaluate the changes of mitochondria DNA (mtDNA), reactive oxygen species
      (ROS) level, adenosine triphosphate (ATP) content and gene (Acsl3, Acadsb, Acaa2,
      Glut1) expression level at different stages after delipation. Results showed that
      no effect was observed on the cleavage ability, but significant lower blastocyst
      rate was obtained in delipated embryos. Copy number of mtDNA decreased gradually
      from MII to four-cell stages and subsequently kept consistent with blastocyst
      stage both in delipated and control embryos, but the copy number of mtDNA in
      delipated embryos was similar to that in the control groups no matter at which
      developmental stage was observed. Both in delipated and control embryos, ATP
      content progressive decreased from one-cell to blastocyst stages, while just at
      one-cell stage, a significant decrease of ATP level was observed in delipated
      embryos compared with that of control. The level of ROS increased obviously after
      delipation at cleavage stage, but no difference was seen at blastocyst stage.
      Finally, the expression level of genes related to fatty acids beta-oxidation
      (Acadsb and Acaa2) was decreased, while the expression level of genes related to
      glucose metabolism (Glut 1) was upregulated after delipation. In conclusion, the
      reduction of lipids in pig oocytes will affect the developmental competence of
      pig PA embryos by disturbed energy metabolism and ROS stress. 

PMID- 26303296
TI  - Not there yet: the classification of communication in cerebral palsy.

PMID- 26303294
TI  - Alteration of Aging-Dependent MicroRNAs in Idiopathic Pulmonary Fibrosis.
AB  - Preclinical Research Idiopathic Pulmonary Fibrosis (IPF) is the most severe
      fibrotic lung disease and characterized by the accumulation of (myo)fibroblasts
      and collagen within the alveolar wall resulting in obliteration of the gas
      exchange surface. Although the detailed pathogenesis is not understood, recent
      studies have found that several microRNAs (miRNAs) are associated with the
      progression of lung diseases including IPF. IPF is a fibrotic disease and, most
      frequently found in an aged population. In this review, the functional roles of
      miRNAs that are deregulated in IPF progression are discussed together with how
      aging affects the miRNA signature, altering the fibroblast phenotype and
      promoting lung fibrosis. Finally, the possibility of targeting miRNAs as a
      therapeutic approach for the treatment of IPF is discussed.

PMID- 26303297
TI  - TCP15 modulates cytokinin and auxin responses during gynoecium development in
      Arabidopsis.
AB  - We studied the role of Arabidopsis thaliana TCP15, a member of the TEOSINTE
      BRANCHED1-CYCLOIDEA-PCF (TCP) transcription factor family, in gynoecium
      development. Plants that express TCP15 from the 35S CaMV promoter (35S:TCP15)
      develop flowers with defects in carpel fusion and a reduced number of stigmatic
      papillae. In contrast, the expression of TCP15 fused to a repressor domain from
      its own promoter causes the development of outgrowths topped with stigmatic
      papillae from the replum. 35S:TCP15 plants show lower levels of the auxin
      indoleacetic acid and reduced expression of the auxin reporter DR5 and the auxin
      biosynthesis genes YUCCA1 and YUCCA4, suggesting that TCP15 is a repressor of
      auxin biosynthesis. Treatment of plants with cytokinin enhances the developmental
      effects of expressing TCP15 or its repressor form. In addition, treatment of a
      knock-out double mutant in TCP15 and the related gene TCP14 with cytokinin causes
      replum enlargement, increased development of outgrowths, and the induction of the
      auxin biosynthesis genes YUCCA1 and YUCCA4. A comparison of the phenotypes
      observed after cytokinin treatment of plants with altered expression levels of
      TCP15 and auxin biosynthesis genes suggests that TCP15 modulates gynoecium
      development by influencing auxin homeostasis. We propose that the correct
      development of the different tissues of the gynoecium requires a balance between
      auxin levels and cytokinin responses, and that TCP15 participates in a feedback
      loop that helps to adjust this balance. 

PMID- 26303298
TI  - Exogenous melatonin inhibits neutrophil migration through suppression of ERK
      activation.
AB  - Neutrophil migration to inflammatory sites is the fundamental process of innate
      immunity among organisms against pathogen invasion. As a major sleep adjusting
      hormone, melatonin has also been proved to be involved in various inflammatory
      events. This study aimed to evaluate the impact of exogenous melatonin on
      neutrophil migration to the injury site in live zebrafish and further investigate
      whether ERK signaling is involved in this process. Using the tail fin transection
      model, the fluorescently labeled neutrophil was in vivo visualized in transgenic
      Tg(lyz:EGFP), Tg(lyz:DsRed) zebrafish. We found that exogenous melatonin
      administration dramatically inhibited the injury-induced neutrophil migration in
      a dose-dependent and time-dependent manner. The inhibited effect of melatonin on
      neutrophil migration could be attenuated by melatonin receptor 1, 2, and 3
      antagonists. The ERK phosphorylation level was significantly decreased post
      injury when treated with melatonin. The blocking of ERK activation with inhibitor
      PD0325901 suppressed the number of migrated neutrophils in response to injury.
      However, the activation of ERK with the epidermal growth factor could impair the
      inhibited effect of melatonin on neutrophil migration. We also detected that
      PD0325901 significantly suppressed the in vivo neutrophils transmigrating over
      the vessel endothelial cell using the transgenic Tg(flk:EGFP);(lyz:DsRed) line
      labeled as both vessel and neutrophil. Taking all of these data together, the
      results indicated that exogenous melatonin had an anti-migratory effect on
      neutrophils by blocking the ERK phosphorylation signal, and it led to the
      subsequent adhesion molecule expression. Thus, the crossing of the vessel
      endothelial cells of neutrophils became difficult. 

PMID- 26303301
TI  - European College of Orthodontics: Commission of Affiliation and Titularisation.
AB  - Date of birth: 29 November 1994; sex: female. A. PRETREATMENT RECORDS: 9 years 6
      months; 5/2006. DIAGNOSIS: Angle Class II; Tooth-arch discrepancy; Teeth missing
      prior to treatment: none. TREATMENT PLAN: Extractions of 14-24-35-45; Appliances
      and devices: bimaxillary multibracket appliances. B. POST-TREATMENT RECORDS:
      3/2008; 22 months. DURATION OF ACTIVE TREATMENT: 22 months. RETENTION: Maxillary:
      thermoformed slip-cover retainer; Mandibular: mandibular: wire bonded from 33 to
      43. C. POST-RETENTION RECORDS: 4/2013; 16 years 5 months; Duration of retention:
      3 years 10 months.

PMID- 26303299
TI  - G protein-coupled estrogen receptor inhibits vascular prostanoid production and
      activity.
AB  - Complications of atherosclerotic vascular disease, such as myocardial infarction
      and stroke, are the most common causes of death in postmenopausal women.
      Endogenous estrogens inhibit vascular inflammation-driven atherogenesis, a
      process that involves cyclooxygenase (COX)-derived vasoconstrictor prostanoids
      such as thromboxane A2. Here, we studied whether the G protein-coupled estrogen
      receptor (GPER) mediates estrogen-dependent inhibitory effects on prostanoid
      production and activity under pro-inflammatory conditions. Effects of estrogen on
      production of thromboxane A(2) were determined in human endothelial cells
      stimulated by the pro-inflammatory cytokine tumour necrosis factor alpha (TNF
      alpha). Moreover, Gper-deficient (Gper(-/-)) and WT mice were fed a pro
      inflammatory diet and underwent ovariectomy or sham surgery to unmask the role of
      endogenous estrogens. Thereafter, contractions to acetylcholine-stimulated
      endothelial vasoconstrictor prostanoids and the thromboxane-prostanoid receptor
      agonist U46619 were recorded in isolated carotid arteries. In endothelial cells,
      TNF-alpha-stimulated thromboxane A2 production was inhibited by estrogen, an
      effect blocked by the GPER-selective antagonist G36. In ovary-intact mice,
      deletion of Gper increased prostanoid-dependent contractions by twofold.
      Ovariectomy also augmented prostanoid-dependent contractions by twofold in WT
      mice but had no additional effect in Gper(-/-) mice. These contractions were
      blocked by the COX inhibitor meclofenamate and unaffected by the nitric oxide
      synthase inhibitor l-N(G)-nitroarginine methyl ester. Vasoconstrictor responses
      to U46619 did not differ between groups, indicating intact signaling downstream
      of thromboxane-prostanoid receptor activation. In summary, under pro-inflammatory
      conditions, estrogen inhibits vasoconstrictor prostanoid production in
      endothelial cells and activity in intact arteries through GPER. Selective
      activation of GPER may therefore be considered as a novel strategy to treat
      increased prostanoid-dependent vasomotor tone or vascular disease in
      postmenopausal women.

PMID- 26303302
TI  - Temporal trend of mortality from major cancers in Xuanwei, China.
AB  - Although a number of studies have examined the etiology of lung cancer in Xuanwei
      County, China, other types of cancer in this county have not been reported
      systematically. This study aimed to investigate the temporal trend of eight major
      cancers in Xuanwei County using data from three mortality surveys (1973-1975,
      1990-1992, and 2004-2005). The Chinese population in 1990 was used as a standard
      population to calculate agestandardized mortality rates. Cancers of lung, liver,
      breast, brain, esophagus, leukemia, rectum, and stomach were identified as the
      leading cancers in this county in terms of mortality rate. During the three time
      periods, lung cancer remained as the most common type of cancer. The mortality
      rates for all other types of cancer were lower than those of the national
      average, but an increasing trend was observed for all the cancers, particularly
      from 1990-1992 to 2004-2005. The temporal trend could be partly explained by
      changes in risk factors, but it also may be due to the improvement in cancer
      diagnosis and screening. Further epidemiological studies are warranted to
      systematically examine the underlying reasons for the temporal trend of the major
      cancers in Xuanwei County. 

PMID- 26303303
TI  - Preliminary evaluation of the publicly available Laboratory for Breast
      Radiodensity Assessment (LIBRA) software tool: comparison of fully automated area
      and volumetric density measures in a case-control study with digital mammography.
AB  - INTRODUCTION: Breast density, commonly quantified as the percentage of
      mammographically dense tissue area, is a strong breast cancer risk factor. We
      investigated associations between breast cancer and fully automated measures of
      breast density made by a new publicly available software tool, the Laboratory for
      Individualized Breast Radiodensity Assessment (LIBRA). METHODS: Digital
      mammograms from 106 invasive breast cancer cases and 318 age-matched controls
      were retrospectively analyzed. Density estimates acquired by LIBRA were compared
      with commercially available software and standard Breast Imaging-Reporting and
      Data System (BI-RADS) density estimates. Associations between the different
      density measures and breast cancer were evaluated by using logistic regression
      after adjustment for Gail risk factors and body mass index (BMI). Area under the
      curve (AUC) of the receiver operating characteristic (ROC) was used to assess
      discriminatory capacity, and odds ratios (ORs) for each density measure are
      provided. RESULTS: All automated density measures had a significant association
      with breast cancer (OR = 1.47-2.23, AUC = 0.59-0.71, P < 0.01) which was
      strengthened after adjustment for Gail risk factors and BMI (OR = 1.96-2.64, AUC
      = 0.82-0.85, P < 0.001). In multivariable analysis, absolute dense area (OR =
      1.84, P < 0.001) and absolute dense volume (OR = 1.67, P = 0.003) were jointly
      associated with breast cancer (AUC = 0.77, P < 0.01), having a larger
      discriminatory capacity than models considering the Gail risk factors alone (AUC
      = 0.64, P < 0.001) or the Gail risk factors plus standard area percent density
      (AUC = 0.68, P = 0.01). After BMI was further adjusted for, absolute dense area
      retained significance (OR = 2.18, P < 0.001) and volume percent density
      approached significance (OR = 1.47, P = 0.06). This combined area-volume density
      model also had a significantly (P < 0.001) improved discriminatory capacity (AUC
      = 0.86) relative to a model considering the Gail risk factors plus BMI (AUC =
      0.80). CONCLUSIONS: Our study suggests that new automated density measures may
      ultimately augment the current standard breast cancer risk factors. In addition,
      the ability to fully automate density estimation with digital mammography,
      particularly through the use of publically available breast density estimation
      software, could accelerate the translation of density reporting in routine breast
      cancer screening and surveillance protocols and facilitate broader research into
      the use of breast density as a risk factor for breast cancer.

PMID- 26303305
TI  - Behavioral, endocrine, and neuronal alterations in zebrafish (Danio rerio)
      following sub-chronic coadministration of fluoxetine and ketamine.
AB  - Most existing pharmacological treatments have focused on the "monoamine
      hypothesis" for targeted drug design for major depressive disorder (MDD). Many of
      these medications have a delayed onset-of-action and limited efficacy.
      Antidepressants with principal targets outside the monoamine system may offer the
      potential for more rapid activity with improved therapeutic benefit. Growing
      evidence suggests that the glutamatergic system is uniquely central to the
      neurobiology and treatment of MDD. Ketamine (Ketalar(r)) is a non-competitive
      glutamatergic antagonist classically used to induce sedation. However,
      preliminary clinical evidence has been promising with regard to its rapidly
      acting antidepressant profile. Zebrafish (Danio rerio) have emerged as a
      promising new animal model to screen the effects of numerous psychotropic
      compounds. This study aimed to determine if a sub-chronic low (sub-anesthetic)
      dose of ketamine could be used to augment the antidepressant effects of the
      widely used antidepressant fluoxetine (Prozac(r)) in adult zebrafish, employing
      an ethanol withdrawal model. Sub-chronic exposure to dosages of 100MUg/L
      fluoxetine and 20mg/L of ketamine reduced anxiety/depression-like behaviors,
      leads to upregulation of serotonin synthesis and elevated whole-body cortisol
      levels. These results demonstrate the utility of zebrafish as a model for
      neuropharmacological research, and the possible efficacy of fluoxetine and
      ketamine coadministration. 

PMID- 26303304
TI  - A D2-like receptor family agonist produces analgesia in mechanonociception but
      not in thermonociception at the spinal cord level in rats.
AB  - The administration of dopaminergic drugs produces analgesia in individuals
      experiencing different types of pain. Analgesia induced by these drugs at the
      spinal cord level is mediated by D2-like agonists, which specifically inhibit the
      detection of nociceptive stimuli by sensory afferents. The extent of the
      analgesia provided by spinal dopamine agonists remains controversial, and the
      cellular mechanism of this analgesic process is poorly understood. The objective
      of this study was to evaluate the analgesic effect of quinpirole, a D2-like
      agonist, based on two nociceptive tests and at various doses that were selected
      to specifically activate dopamine receptors. We found that intrathecal quinpirole
      administration produces analgesia of mechanical but not thermal nociception and
      that the analgesic effect of quinpirole is reversed by a mix of D2, D3, and D4
      receptor-specific antagonists, suggesting that the activation of all D2-like
      receptors is involved in the analgesia produced by intrathecal quinpirole. The
      differential effect on thermal and mechanical nociception was also tested upon
      the activation of MU-opioid receptors. As reported previously, low doses of the
      MU-opioid receptor agonist DAMGO produced analgesia of only thermonociception.
      This evidence shows that a D2-like receptor agonist administered at the spinal
      cord level produces analgesia specific to mechanonociception but not
      thermonociception.

PMID- 26303306
TI  - Hydroxyurea therapy for children with sickle cell disease: describing how
      caregivers make this decision.
AB  - BACKGROUND: Hydroxyurea (HU) is underutilized in children with sickle cell
      disease (SCD) because caregivers frequently decline HU when it is offered. This
      study explores what impacts this decision. RESULTS: Caregivers of children with
      clinically severe SCD whose children were offered HU previously were interviewed.
      We used a qualitative analytical approach to analyze their telephone interview
      transcripts. Caregivers who chose HU (n = 9) reported their children had severe
      SCD, sought detailed information about HU, and accepted HU as a preventative
      therapy. In contrast, caregivers who did not choose HU (n = 10) did not perceive
      their children as having severe SCD and did not question their child's provider
      about HU. CONCLUSIONS: This study identifies specific areas that providers should
      address to when they discuss HU with families so that they can make informed
      decisions. Our study also uncovered factors that are important to consider when
      designing future interventions to improve hydroxyurea acceptance and when
      developing decision-aid tools to assist caregivers of children with SCD who are
      considering disease modifying therapies.

PMID- 26303308
TI  - Induction of Regulatory B-Cells by Mesenchymal Stem Cells is Affected by SDF
      1alpha-CXCR7.
AB  - BACKGROUND/AIMS: Mesenchymal stem cells (MSCs) possess immunomodulatory
      properties on a diverse array of immune cell lineages, including regulatory T and
      B cells (Tregs and Bregs, respectively). However, their specific effects and
      mechanisms underlying induction of Bregs remain unclear. The immune regulatory
      function of MSCs is exerted through both cell-cell contact and the release of
      soluble factors. The main objective of this study was to examine the role of the
      SDF-1-CXCR4/CXCR7 axis in the secretory action of MSCs, and potential effects on
      the immunoregulatory function of these cells. METHODS: MSCs were isolated from
      mouse bone marrow and characterized according to their multilineage
      differentiation potential and their surface antigen expression. CD19(+) B cells
      purified from mice splenocytes were co-cultured with MSCs at various ratios in
      the presence of LPS and alphaCD40. After 4 days, intracellular IL-10 production
      and cell surface CD1d and CD5 expression by CD19(+) B cells were determined using
      flow cytometry, and the secretion of IL-10, IL-6, IgM, and IgG were assessed with
      ELISA. MSCs were treated with different concentrations of stromal derived factor
      1alpha (SDF-1alpha) stimuli or transiently overexpressed with CXCR7. and their
      cell viability and immune regulatory effects of MSCs on Bregs were assessed.
      RESULTS: MSCs induced IL-10-producing regulatory B cells and primarily stimulated
      the CD1d(+)CD5(+)B cell subset of IL-10+Breg cells to express IL-10. IL-10, IL-6,
      and IgM secretion were additionally induced by MSCs. The CXCR7 pathway was
      required for MSC viability and the production of paracrine factors under SDF
      1alpha culture condition. Low concentrations of SDF-1alpha promoted the
      immunomodulatory effect of MSCs, leading to a further increase in IL-10-producing
      regulatory B cells and IL-10 secretion. In contrast, high concentrations of SDF
      1alpha inhibited MSCs induction of IL-10(+)Breg cells. Notably, CXCR7
      overexpression in MSCs reversed the inhibitory effect of high concentrations of
      SDF-1alpha and promoted the immunomodulatory effect of these cells. CONCLUSION:
      MSCs induce IL-10(+)Breg cells, which contribute to the generation of an
      immunosuppressive environment. SDF-1alpha and its receptor, CXCR7 play important
      roles in the immunomodulatory function of MSCs by regulating their paracrine
      actions.

PMID- 26303309
TI  - Contemporary perspective and management of testosterone deficiency: Modifiable
      factors and variable management.
AB  - Testosterone deficiency can occur in males of all ages. In adult males, it is
      induced by endogenous testosterone decline through aging and other modifiable
      factors. Recent publications suggested the importance of the magnitude of
      longitudinal decline of testosterone from baseline. The baseline level and the
      longitudinal decline have individual variability influenced by individual factors
      including digit ratio, CAG repeat of the androgen receptor and sirtuin activity.
      Regarding treatment for testosterone deficiency, testosterone replacement therapy
      is the gold standard for the management of testosterone-deficient patients, and
      it improves three domains of testosterone deficiency symptoms, such as the
      physical, psychological and sexual domain. Recent reports suggested the
      importance of modifiable factors in the testosterone decline in addition to
      aging. Therefore, it might be responsible for the prevention of testosterone
      deficiency symptoms to maintain testosterone secretion taking account of the
      modifiable factors. The present article reviews the literature, and introduces
      contemporary perspectives and management of testosterone deficiency. 

PMID- 26303307
TI  - Neuronal and Cardiovascular Potassium Channels as Therapeutic Drug Targets:
      Promise and Pitfalls.
AB  - Potassium (K(+)) channels, with their diversity, often tissue-defined
      distribution, and critical role in controlling cellular excitability, have long
      held promise of being important drug targets for the treatment of dysrhythmias in
      the heart and abnormal neuronal activity within the brain. With the exception of
      drugs that target one particular class, ATP-sensitive K(+) (KATP) channels, very
      few selective K(+) channel activators or inhibitors are currently licensed for
      clinical use in cardiovascular and neurological disease. Here we review what a
      range of human genetic disorders have told us about the role of specific K(+)
      channel subunits, explore the potential of activators and inhibitors of specific
      channel populations as a therapeutic strategy, and discuss possible reasons for
      the difficulty in designing clinically relevant K(+) channel modulators. 

PMID- 26303310
TI  - Non-enteric infections, antibiotic use, and risk of development of functional
      gastrointestinal disorders.
AB  - BACKGROUND: Gastrointestinal infections are risk factors for irritable bowel
      syndrome (IBS) and functional dyspepsia (FD). We investigated whether non-enteric
      infections and antibiotic exposure are also associated with the development of
      functional gastrointestinal disorders (FGIDs). METHODS: In a nested case-control
      study, random samples of Olmsted County, MN, were mailed valid self-report
      questionnaires from 1988 through 1994, and then follow-up questionnaires from
      1995 through 2003. Survey responders who did not report any FGID symptoms at
      baseline, but then reported such symptoms in at least one subsequent survey, were
      classified as new-onset cases. Age-matched controls were individuals who did not
      have symptoms at either the initial or subsequent surveys. KEY RESULTS: The
      overall response rate was 78% to the initial survey and 52% to the follow-up
      survey. Based on the responses, 316 participants had a new onset of an FGID (43
      IBS constipation, 95 IBS diarrhea, 25 IBS mixed, and 153 other FGIDs, including
      FD) and 250 did not (controls). Around 76% (241/316) of cases reported a non
      enteric infection vs 66% (166/250) of the controls. The frequency of enteric
      infections was similar between the two groups. Of the new FGID cases, 83% had a
      non-enteric infection that was treated with antibiotic. In a logistic regression
      model, treatment with antibiotics for a non-gastrointestinal infection was
      associated with the development of an FGID (odds ratio = 1.90; 95% CI: 1.21-2.98;
      p = 0.005), after adjusting for age and sex. CONCLUSIONS & INFERENCES: Based on a
      case-control study, treatment of a non-gastrointestinal infection with
      antibiotics appears to be a risk factor for development of an FGID.

PMID- 26303311
TI  - Comparison of two maxillary protraction protocols: tooth-borne versus bone
      anchored protraction facemask treatment.
AB  - BACKGROUND: Protraction facemask has been advocated for treatment of class III
      malocclusion with maxillary deficiency. Studies using tooth-borne rapid palatal
      expansion (RPE) appliance as anchorage have experienced side effects such as
      forward movement of the maxillary molars, excessive proclination of the maxillary
      incisors, and an increase in lower face height. A new Hybrid Hyrax bone-anchored
      RPE appliance claimed to minimize the side effects of maxillary expansion and
      protraction. A retrospective study was conducted to compare the skeletal and
      dentoalveolar changes in patients treated with these two protocols. METHODS:
      Twenty class III patients (8 males, 12 females, mean age 9.8 +/- 1.6 years) who
      were treated consecutively with the tooth-borne maxillary RPE and protraction
      device were compared with 20 class III patients (8 males, 12 females, mean age
      9.6 +/- 1.2 years) who were treated consecutively with the bone-anchored
      maxillary RPE and protraction appliances. Lateral cephalograms were taken at the
      start of treatment and at the end of maxillary protraction. A control group of
      class III patients with no treatment was included to subtract changes due to
      growth to obtain the true appliance effect. A custom cephalometric analysis based
      on measurements described by Bjork and Pancherz, McNamara, Tweed, and Steiner
      analyses was used to determine skeletal and dental changes. Data were analyzed
      using a one-way analysis of variance. RESULTS: Significant differences between
      the two groups were found in 8 out of 29 cephalometric variables (p < .05).
      Subjects in the tooth-borne facemask group had more proclination of maxillary
      incisors (OLp-Is, Is-SNL), increase in overjet correction, and correction in
      molar relationship. Subjects in the bone-anchored facemask group had less
      downward movement of the "A" point, less opening of the mandibular plane (SNL-ML
      and FH-ML), and more vertical eruption of the maxillary incisors. CONCLUSIONS:
      The Hybrid Hyrax bone-anchored RPE appliance minimized the side effect encounter
      by tooth-borne RPE appliance for maxillary expansion and protraction and may
      serve as an alternative treatment appliance for correcting class III patients
      with a hyperdivergent growth pattern.

PMID- 26303313
TI  - Approaches for predicting effects of unintended environmental exposure to an
      endocrine active pharmaceutical, tamoxifen.
AB  - Tamoxifen is an endocrine-active pharmaceutical (EAP) that is used world-wide.
      Because tamoxifen is a ubiquitous pharmaceutical and interacts with estrogen
      receptors, a case study was conducted with this compound to (1) determine effects
      on reproductive endpoints in a nontarget species (i.e., a fish), (2) compare
      biologically-active metabolites across species, (3) assess whether in vitro
      assays predict in vivo results, and (4) investigate metabolomic profiles in
      tamoxifen-treated fish to better understand the biological mechanisms of
      tamoxifen toxicity. In reproductive assays, tamoxifen exposure caused a
      significant reduction in egg production and significantly increased ovarian
      aromatase activity in spawning adult cunner fish (Tautogolabrus adspersus). In
      plasma from tamoxifen-exposed cunner, the predominant metabolite was 4
      hydroxytamoxifen, while in rats it was N-desmethyltamoxifen. Because 4
      hydroxytamoxifen is a more biologically active metabolite than N
      desmethyltamoxifen, this difference could result in a different level of risk for
      the two species. The results of in vitro assays with fish hepatic microsomes to
      assess tamoxifen metabolism did not match in vivo results, indicating probable
      differences in excretion of tamoxifen metabolites in fish compared with rats. For
      the first time, a complete in vitro characterization of the metabolism of
      tamoxifen using fish microsomes is presented. Furthermore, a metabolomic
      investigation of cunner gonad extracts demonstrates that tamoxifen alters the
      biochemical profile in this nontarget species. Understanding the consequence of
      tamoxifen exposure in nontarget species, and assessing the discrepancies between
      sex- and species-mediated endpoints, is a step toward understanding how to
      accurately assess the risks posed by EAPs, such as tamoxifen, in the aquatic
      environment. (c) 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1834-1850,
      2016.

PMID- 26303314
TI  - Egypt's Popular Uprising and the Stakes of Medical Neutrality.
AB  - Amidst the recent political uprisings in the Arab region, physicians and other
      healthcare workers have found themselves in the crossfire. This paper focuses on
      Egypt's doctors, paying special attention to how many have both appealed to and
      practiced medical neutrality as its own potent and contested political stance,
      particularly since the period of military rule following Mubarak's removal from
      power. Our paper draws on interviews with physicians who served as volunteers in
      the field hospitals in the days of unrest and violence, and with others who
      played a major role in documenting protesters' injuries, police brutality, and
      other forms of state violence against unarmed citizens. Based on interviews with
      doctors who belong to organizations such as "Tahrir Doctors" and "Doctors Without
      Rights," our paper reveals how these doctors' commitment to professional ethics
      put them at odds with the orders of military personnel, rendering their appeal to
      "medical neutrality" a weighty political act in and of itself. 

PMID- 26303315
TI  - Conflicting Notions on Violence and PTSD in the Military: Institutional and
      Personal Narratives of Combat-Related Illness.
AB  - Research indicates that soldiers struggling with PTSD under-utilize mental health
      care. Quantitative studies of barriers to care point to the importance of
      soldiers' beliefs about mental health and mental health interventions in their
      care-seeking behavior, yet these studies still struggle to understand the
      particular beliefs involved and the ways they impact care-seeking behavior. This
      preliminary study makes a start in examining these questions through qualitative
      literature analysis. It maps out dominant messages surrounding PTSD in military
      mental health interventions, and explores how they can both shape and conflict
      with soldiers' personal notions. It does so by analyzing these messages and
      notions as institutional and personal (illness) narratives. Institutional
      military PTSD-narratives, which draw on mainstream scientific and clinical
      models, appear to communicate contradictory notions on the meanings of violence
      and its psychological consequences, often without acknowledging these
      contradictions. As such, these narratives seem to shape struggles of soldiers,
      both within themselves and with the military institution. The identified
      conflicts indicate, contrary to the individualizing and decontextualizing focus
      of dominant PTSD-understandings, that soldiers' struggles also have social and
      moral dimensions. This has important implications for both research into PTSD
      interventions and understandings of PTSD as such. 

PMID- 26303316
TI  - Cytomorphologic findings of malignant mesothelioma in FNA biopsies and touch
      preps of core biopsies.
AB  - BACKGROUND: Given the lack of recent literature regarding the aspiration cytology
      of immunohistochemically confirmed malignant mesothelioma (MM), we were
      interested in reviewing the experience of our institution and establishing useful
      morphologic criteria. METHODS: Seventeen aspiration and touch preparation
      specimens with a diagnosis of MM obtained between 2002-2013 were reviewed along
      with 20 cases of adenocarcinoma and 16 cases of squamous cell carcinoma. The
      utility of a number of morphologic features was evaluated. RESULTS: In most cases
      of MM, a consistent pattern emerged. Aspirates and touch preps were cellular with
      irregularly shaped 2 and 3 dimensional clusters. The individual cells were
      predominantly angulated and had dense cytoplasm with eccentric nuclei. In every
      case, a minority of tumor cells contained prominent microvacuoles. The chromatin
      pattern tended to be fine with small nucleoli. While most cases were
      cytologically monotonous, five cases displayed striking pleomorphism and three
      cases contained occasional large atypical cells. Two cases contained
      metachromatic background material. Features which were most useful in
      discriminating MM from adenocarcinoma were angulated cell shape(P = 0.0002),
      dense cytoplasm(P = 0.0001), and cytoplasmic microvacuoles(P = 0.0001). In our
      material, cases of squamous cell carcinoma were often difficult to distinguish
      from MM. Useful discriminatory features present in squamous cell carcinoma
      included ink dot nuclei(P = 0.0003), a "dirty" cystic, necrotic background (P =
      0.0027) and tumor balls with peripheral spindling(P = 0.0041). CONCLUSION: Most
      cases of MM have a consistent appearance in core biopsy touch preps and FNAs.
      Distinguishing MM from adenocarcinoma and squamous cell carcinoma can be
      facilitated by evaluating a few key morphologic features.

PMID- 26303312
TI  - Stress exposure, food intake and emotional state.
AB  - This manuscript summarizes the proceedings of the symposium entitled, "Stress,
      Palatable Food and Reward", that was chaired by Drs. Linda Rinaman and Yvonne
      Ulrich-Lai at the 2014 Neurobiology of Stress Workshop held in Cincinnati, OH.
      This symposium comprised research presentations by four neuroscientists whose
      work focuses on the biological bases for complex interactions among stress, food
      intake and emotion. First, Dr Ulrich-Lai describes her rodent research exploring
      mechanisms by which the rewarding properties of sweet palatable foods confer
      stress relief. Second, Dr Stephanie Fulton discusses her work in which excessive,
      long-term intake of dietary lipids, as well as their subsequent withdrawal,
      promotes stress-related outcomes in mice. Third, Dr Mark Wilson describes his
      group's research examining the effects of social hierarchy-related stress on food
      intake and diet choice in group-housed female rhesus macaques, and compared the
      data from monkeys to results obtained in analogous work using rodents. Finally,
      Dr Gorica Petrovich discusses her research program that is aimed at defining
      cortical-amygdalar-hypothalamic circuitry responsible for curbing food intake
      during emotional threat (i.e. fear anticipation) in rats. Their collective
      results reveal the complexity of physiological and behavioral interactions that
      link stress, food intake and emotional state, and suggest new avenues of research
      to probe the impact of genetic, metabolic, social, experiential and environmental
      factors on these interactions. 

PMID- 26303317
TI  - Quantitative characterization of carbon/carbon composites matrix texture based on
      image analysis using polarized light microscope.
AB  - A quantitative characteristic method was proposed for characterizing the matrix
      texture of carbon/carbon(C/C) composites, which determined the mechanical and
      physical properties of C/C composites. Based on the cloud theory that was
      commonly used for uncertain reasoning and the transformation between quantitative
      and qualitative characterization, so the relationship between the extinction
      angle and texture types was built by the cloud models for describing the texture
      of microstructure, moreover, linguistic controllers were established to analyze
      the matrix texture in accordance with the features of the polarized light
      microscope (PLM) image. On this basis, the extinction angle could be calculated
      from the PLM image of the C/C composites. In contrast to the results of
      measurement, the errors between calculative values and measured values were
      maintained 1-2 degrees  in basically. Meanwhile, the PLM image of C/C composites
      was segmented by the component, in particular, the matrix with mixed textures was
      further segmented by the difference of texture. It means that the quantitative
      characterization of C/C composites matrix based on single PLM image has been
      realized.

PMID- 26303318
TI  - Stepwise Therapy for Treating Tuberculosis of the Upper Cervical Spine: A
      Retrospective Study of 11 Patients.
AB  - AIMS: Tuberculosis of the upper cervical spine is a rare occurrence with serious
      consequence, and its optimal treatment protocol remains inconclusive. This study
      aims at investigating the clinical characteristics and management outcomes of the
      stepwise therapy for different stages of tuberculosis of the upper cervical
      spine. METHODS: We conducted a retrospective analysis of 11 patients with
      tuberculosis of the upper cervical spine who received anti-tuberculosis
      chemotherapy for 15 months. Two infants were treated by individualized
      chemotherapy, while 9 patients with retropharyngeal abscess were first treated
      with CT-guided percutaneous puncture, and the catheter was used to administer
      local chemotherapy. Two of these 9 patients continued to receive posterior
      instrumentation due to atlantoaxial subluxation. Patients were followed up
      clinically and radiologically for an average period of 60 months. RESULTS: Two
      patients underwent catheter change due to catheter falling off and blockage, 2
      patients had gastrointestinal side effects, and 2 patients had drug-induced
      hepatitis derived from the chemotherapy. Mean erythrocyte sedimentation rate was
      10.27 mm/h (range 4-16 mm/h) and average visual analogue scale score was 2.55. A
      total of 11 cases underwent routine anti-tuberculosis chemotherapy for 15 months.
      9 of 11 cases received supplementary surgical therapy, and all patients were
      cured at the final follow-up. CONCLUSION: Standard anti-tuberculosis chemotherapy
      is the cornerstone of stepwise therapy for tuberculosis of the upper cervical
      spine. Local chemotherapy is effective and minimally invasive for patients with
      severe local symptoms without spinal cord compression. Just as in patients with
      atlantoaxial instability, open fixation and bone grafting are necessary.

PMID- 26303319
TI  - Pathophysiology of Calcium, Phosphorus, and Magnesium Dysregulation in Chronic
      Kidney Disease.
AB  - Calcium, phosphorus, and magnesium homeostasis is altered in chronic kidney
      disease (CKD). Hypocalcemia, hyperphosphatemia, and hypermagnesemia are not seen
      until advanced CKD because adaptations develop. Increased parathyroid hormone
      (PTH) secretion maintains serum calcium normal by increasing calcium efflux from
      bone, renal calcium reabsorption, and phosphate excretion. Similarly, renal
      phosphate excretion in CKD is maintained by increased secretion of fibroblast
      growth factor 23 (FGF23) and PTH. However, the phosphaturic effect of FGF23 is
      reduced by downregulation of its cofactor Klotho necessary for binding FGF23 to
      FGF receptors. Intestinal phosphate absorption is diminished in CKD due in part
      to reduced levels of 1,25 dihydroxyvitamin D. Unlike calcium and phosphorus,
      magnesium is not regulated by a hormone, but fractional excretion of magnesium
      increases as CKD progresses. As 60-70% of magnesium is reabsorbed in the thick
      ascending limb of Henle, activation of the calcium-sensing receptor by magnesium
      may facilitate magnesium excretion in CKD. Modification of the TRPM6 channel in
      the distal tubule may also have a role. Besides abnormal bone morphology and
      vascular calcification, abnormalities in mineral homeostasis are associated with
      increased cardiovascular risk, increased mortality and progression of CKD.

PMID- 26303321
TI  - Risk factors for mortality in cattle during live export from Australia by sea.
AB  - OBJECTIVE: This study investigated mortality trends and risk factors for death
      for cattle exported live from Australia by sea. METHODS: Mortality data for all
      voyages from Australia to all destinations between 1995 and 2012 were analysed
      retrospectively. Daily mortality trends were assessed for 20 long-haul voyages
      from Australia to the Middle East and to the Russian Federation between 2010 and
      2012. RESULTS: The overall voyage mortality percentage was 0.17% across the 13
      million cattle exported on 6447 voyages. Mortality rates decreased significantly
      after 2000 and stabilised at low levels from 2003. The mortality rate for voyages
      to the Middle East and north Africa (0.44%) was significantly higher than for
      voyages to south-east Europe (0.28%), north-east Asia (0.12%) and south-east Asia
      (0.09%). Cattle exported from ports in southern Australia carried a higher
      mortality risk than those exported from northern ports for both long- and short
      haul voyages. The daily mortality rate on long-haul voyages peaked at 3-4 weeks
      post-departure, although there was a smaller peak at 1-2 weeks. CONCLUSION: The
      marked reduction in mortality rate since 2000 is related to a number of factors,
      including industry initiatives, government legislation and market demand, that
      have resulted in changes to both the selection of cattle for export and the
      management of cattle prior to and during voyages. Routine collection of animal
      performance data, combined with NLIS records and use of methods described here,
      have the potential to contribute to more effective management of mortality risks
      across the export chain.

PMID- 26303320
TI  - Cordycepin induced MA-10 mouse Leydig tumor cell apoptosis by regulating p38
      MAPKs and PI3K/AKT signaling pathways.
AB  - The p38 MAPKs play important roles in the regulation of balance between cell
      survival and cell death on the development of various cancers. However, the roles
      of p38 MAPKs regulating apoptotic effects on Leydig tumor cells remain unclear.
      In the present study, we showed that cordycepin (3'-deoxyadenosine) selectively
      induced apoptosis in MA-10 mouse Leydig tumor cells through regulating the p38
      MAPK and PI3K/AKT signaling pathways. Cordycepin reduced viability in MA-10, TM4,
      and NT2/D1 cells, but not cause cell death of primary mouse Leydig cells on
      moderate concentration. Cordycepin increased reactive oxygen species (ROS)
      levels, which is associated with the induction of apoptosis as characterized by
      positive Annexin V binding, activation of caspase-3, and cleavage of PARP.
      Inhibition of p38 MAPKs activity by SB203580 significantly prevented cordycepin
      induced apoptosis in MA-10 cells. Co-treatment with wortmannin or the autophagy
      inhibitor 3-methyladenine (3-MA) elevated levels of apoptosis in cordycepin
      treated MA-10 cells. Moreover, cordycepin activated p53, p21 and TGFbeta; and
      downregulated CDK2. The antitumour activity of cordycepin-treated MA-10 cells was
      significantly distinct in severe combined immunodeficiency (SCID) mice in vivo.
      These results suggested that cordycein is a highly selective treatment to induce
      MA-10 cells apoptosis via p38 MAPKs signaling. 

PMID- 26303322
TI  - Tumebacillus luteolus sp. nov., isolated from soil.
AB  - Two strains of Gram-stain-positive, aerobic, spore-forming and rod-shaped
      bacteria, designated U13T and U14, were isolated from soil of the Ukraine.
      Comparative analysis of the 16S rRNA gene sequences indicated that these strains
      belong to the genus Tumebacillus, with the highest 16S rRNA gene sequence
      similarity with Tumebacillus ginsengisoli Gsoil 1105T (95.48% and 95.49%,
      respectively). Strains U13T and U14 had iso-C15:0 and summed features 1 and 4 as
      the main fatty acids, and were able to grow at pH ranging from pH 5.0 to 9.0
      (optimum pH 6.0-7.0), temperatures ranging from 25 to 42  degrees C (optimum 28
      37  degrees C) and with 0-1% (w/v) NaCl (optimum 0%, w/v) on R2A agar medium.
      Chemotaxonomic data revealed that the cell-wall peptidoglycan type of the two
      strains was type A1gamma (meso-diaminopimelic acid). On the basis of the evidence
      from this study, strains U13T and U14 represent a novel species of the genus
      Tumebacillus, for which the name Tumebacillus luteolus sp. nov. is proposed. The
      type strain is U13T ( = KEMB 7305-100T = JCM 19866T) and a second strain is U14 (
      = KEMB 7305-101 = JCM 19867).

PMID- 26303323
TI  - Refinement of the inversion-transfer NMR experiment for faster characterization
      of chemical exchange.
AB  - It is shown theoretically that the inversion-transfer experiment used to estimate
      the value of unidirectional rate constants in chemical exchange systems can be
      performed faster via a reduction of the recovery delay. The chemical exchange
      rate constants can then be estimated accurately with a formula close to that of
      standard inversion transfer and easy to use, after a justified approximation. A
      function was developed to determine the optimal value of the recovery delay for
      an optimal inversion-transfer sequence. The validity of these theoretical results
      was checked experimentally with a solution of N,N-dimethylacetamide in which
      chemical exchange arises from internal hindered rotation.

PMID- 26303324
TI  - Maximising the diagnostic potential of APTT-based screening assays for activated
      protein C resistance.
AB  - INTRODUCTION: Activated protein C resistance (APC-R) due to FV Leiden is the most
      common hereditary thrombophilia. Rarer FV mutations can also confer APC-R, and
      acquired APC-R is encountered in a number of conditions. APC-R screening with
      clotting tests is common, yet they are prone to interferences and elevated
      baseline clotting times can invalidate testing. METHODS: APTT-based classic APC-R
      (CAPC-R) screening, and modified screening (MAPC-R) employing dilution in FV
      deficient plasma were performed on an automated analyser. Baseline clotting times
      and APC-R ratios of 1340 patients being screened for hereditary and acquired
      thrombophilia were assessed for analytical and diagnostic validity. RESULTS: Most
      patients (1117/1340) had normal baseline clotting times, and in 270 of these
      cases, this was despite the presence of a lupus anticoagulant (LA). FV Leiden was
      genetically confirmed in all patients with reduced CAPC-R and MAPC-R ratios. A
      subgroup with normal CAPC-R but reduced MAPC-R also identified FV Leiden, but
      also other patients with minimally reduced MAPC-R ratios not due to FV Leiden.
      Reduced CAPC-R and normal modified APC-R identified possible acquired APC-R in 49
      patients. LA-positive patients with elevated baseline clotting times did not
      affect distinction between APC-R and normality, although therapeutic
      anticoagulation did invalidate CAPC-R, and occasionally MAPC-R too. CONCLUSIONS:
      Many departments only screen with MAPC-R to detect just FV mutations. Concurrent
      performance of CAPC-R and MAPC-R increases diagnostic capability by detecting
      acquired APC-R. Elevated baseline clotting times can invalidate APC-R ratios,
      although prolongation by LA alone may not.

PMID- 26303325
TI  - Dual-mode chemodosimetric response of dibromo-BODIPY with anions.
AB  - Aromatic nucleophilic substitution (Ar-SN) reaction of 3,5
      dibromopentafluorophenyl-BODIPY has been explored as a remarkable basis for
      selective discrimination of anions. The efficient and characteristic ability of
      anions to modulate the absorption and emission properties of the dye provides an
      instantaneous distinction through dual-modes. For the first time, a novel
      platform to achieve dual-modal and promising recognition with discrimination of a
      series of anions differing in the nucleophilic atoms (F, O, C and N) has been
      taken into consideration. The behaviour of various anions with dibromo-BODIPY and
      vivid signal transduction has been fully established with absorption and emission
      spectroscopy. In addition to this, recognition events have been unambiguously
      characterized by (1)H, (19)F-NMR and single-crystal XRD. 

PMID- 26303327
TI  - Recombinant Newcastle Disease Virus Encoding IL-12 and/or IL-2 as Potential
      Candidate for Hepatoma Carcinoma Therapy.
AB  - Interleukins as immunomodulators are promising therapeutic agents for cancer
      therapy. Previous studies showed that there was an improved antitumor immunity in
      tumor-bearing mice using recombinant Newcastle disease virus carrying for
      interleukin-2. Interleukin-12 is a promising antitumor cytokine too. So we
      investigated and compared the antitumor effect of genetically engineered
      Newcastle disease virus strains expressing both interleukin-12 and/or interleukin
      2 (rClone30-interleukin-2, rClone30-interleukin-12, and rClone30-interleukin-12
      interleukin-2). In vitro studies showed that rClone30s could efficiently infect
      tumor cells and express interleukin-12 and/or interleukin-2. 3-(4,5
      Dimethylthiazol-2-y)-2,5-diphenyl-tetrazolium bromide results showed rClone30s
      possessed strong cytotoxic activities against multiple tumor cell lines (U251,
      HepG2, A549, and Hela). Animal studies showed that rClone30-interleukin-12
      interleukin-2 was more effective in inhibition of murine hepatoma carcinoma
      tumors, with the mean tumor volume (day 14) of 141.70 mm(3) comparing 165.67
      mm(3) of rClone30-interleukin-12 group, 210.47 mm(3) of rClone30-interleukin-2
      group, 574.70 mm(3) of rClone30 group, and 1206.83 mm(3) of phosphate-buffered
      saline group. Moreover, the rClone30-interleukin-12-interleukin-2 treated mice
      secreted more interferon gamma (333.518 pg/mL) and its downstream cytokine
      interferon-gamma induced protein 10 (16.006 pg/mL) in tumor than the rClone30
      interleukin-12 group (interferon gamma: 257.548 pg/mL; interferon-gamma induced
      protein 10: 13.601 pg/mL), rClone30-interleukin2 group (interferon gamma: 124.601
      pg/mL; interferon-gamma induced protein 10: 9.779 pg/mL), or rClone30 group
      (interferon gamma: 48.630 pg/mL; interferon-gamma induced protein 10:1.650
      pg/mL). For the survival study, rClone30-interleukin12-interleukin2 increased the
      survival rate (12 of 16) of the tumor-bearing mice versus 11 of 16 in rClone30
      interleukin-12 group, 10 of 16 in rClone30-interleukin-2 group, 7 of 16 in
      Clone30 group, and 0/16 in phosphate-buffered saline group, respectively. To
      determine whether the mice treated with recombinant virus developed protective
      immune response, the mice were rechallenged with the same tumor cells. The
      results showed that viral-treated mice were significantly protected from
      rechallenge. These results suggest that expressing both interleukin-2 and/or
      interleukin-12 could be ideal approaches to enhance the antitumor ability of
      Newcastle disease virus, and rClone30-interleukin-12-interleukin-2 is slightly
      superior over rClone30-interleukin-12 and rClone30-interleukin-2 alone.

PMID- 26303326
TI  - Comparison of tonic spinal cord stimulation, high-frequency and burst stimulation
      in patients with complex regional pain syndrome: a double-blind, randomised
      placebo controlled trial.
AB  - BACKGROUND: Complex Regional Pain Syndrome (CRPS) is a disabling disease that is
      sometimes difficult to treat. Although spinal cord stimulation (SCS) can reduce
      pain in most patients with CRPS, some do not achieve the desired reduction in
      pain. Moreover, the pain reduction can diminish over time even after an initially
      successful period of SCS. Pain reduction can be regained by increasing the SCS
      frequency, but this has not been investigated in a prospective trial. This study
      compares pain reduction using five SCS frequencies (standard 40 Hz, 500 Hz, 1200
      Hz, burst and placebo stimulation) in patients with CRPS to determine which of
      the modalities is most effective. DESIGN: All patients with a confirmed CRPS
      diagnosis that have unsuccessfully tried all other therapies and are eligible for
      SCS, can enroll in this trial (primary implantation group). CRPS patients that
      already receive SCS therapy, or those previously treated with SCS but with loss
      of therapeutic effect over time, can also participate (re-implantation group).
      Once all inclusion criteria are met and written informed consent obtained,
      patients will undergo a baseline assessment (T0). A 2-week trial with SCS is
      performed and, if successful, a rechargeable internal pulse generator (IPG) is
      implanted. For the following 3 months the patient will have standard 40 Hz
      stimulation therapy before a follow-up assessment (T1) is performed. Those who
      have completed the T1 assessment will enroll in a 10-week crossover period in
      which the five SCS frequencies are tested in five periods, each frequency lasting
      for 2 weeks. At the end of the crossover period, the patient will choose which
      frequency is to be used for stimulation for an additional 3 months, until the T2
      assessment. DISCUSSION: Currently no trials are available that systematically
      investigate the importance of variation in frequency during SCS in patients with
      CRPS. Data from this trial will provide better insight as to whether SCS with a
      higher frequency, or with burst stimulation, results in more effective pain
      relief. TRIAL REGISTRATION: Current Controlled Trials ISRCTN36655259.

PMID- 26303328
TI  - Cell length instead of cell number becomes the predominant factor contributing to
      hypocotyl length genotypic differences under abiotic stress in Medicago
      truncatula.
AB  - Hypocotyl elongation in the dark is a crucial process to ensure seedling
      emergence. It relies both on the cell number and cell length. The contribution of
      these two factors to the maximal hypocotyl length and the impact of environmental
      conditions on this contribution are not known. This is surprising considering the
      agronomic and economical importance of seedling emergence in crop establishment.
      Using 14 genotypes from a nested core collection representing Medicago truncatula
      (barrel medic) natural variation, we investigated how epidermal cell number and
      cell length contribute to hypocotyl length under optimal, low temperature (8
      degrees C) and water deficit (-0.50 MPa) conditions. Both cell number and length
      vary according to genotypes and contribute to maximal hypocotyl length
      differences between genotypes. This contribution, however, depends on growth
      conditions. Cell number is the major contributor under optimal conditions (60%)
      whereas cell length becomes the major determinant under stress. Maximal hypocotyl
      length is correlated with hypocotyl elongation rate under both stresses but not
      under optimal condition, revealing contrasted genotypes for cell elongation
      capacity under stress. To identify the genetic regulators determining cell number
      and cell length, quantitative trait loci (QTLs) were detected using a recombinant
      inbred lines population exhibiting segregation in maximal hypocotyl length. Two
      QTLs controlling cell number and three QTLs controlling cell length at low
      temperature were detected. One QTL for cell number and two for cell length were
      found to be associated with hypocotyl length under low temperature. This study
      provides new information to improve seedling emergence under abiotic stress. 

PMID- 26303329
TI  - Distribution of immunoglobulin G antibody secretory cells in small intestine of
      Bactrian camels (Camelus bactrianus).
AB  - BACKGROUND: To explore the morphological evidence of immunoglobulin G (IgG)
      participating in intestinal mucosal immunity, 8 healthy adult Bactrian camels
      used. First, IgG was successfully isolated from their serum and rabbit antibody
      against Bactrian camels IgG was prepared. The IgG antibody secretory cells (ASCs)
      in small intestine were particularly observed through immumohistochemical
      staining, then after were analyzed by statistical methods. RESULTS: The results
      showed that the IgG ASCs were scattered in the lamina propria (LP) and some of
      them aggregated around of the intestinal glands. The IgG ASCs density was the
      highest from middle segment of duodenum to middle segment of jejunum, and then in
      ended segment of jejunum and initial segment of ileum, the lowest was in initial
      segment of duodenum, in middle and ended segment of ileum. CONCLUSIONS: It was
      demonstrated that the IgG ASCs mainly scattered in the effector sites of the
      mucosal immunity, though the density of IgG ASCs was different in different
      segment of small intestine. Moreover, this scatted distribution characteristic
      would provide a morphology basis for research whether IgG form a full-protection
      and immune surveillance in mucosal immunity homeostasis of integral intestine.

PMID- 26303330
TI  - Effectiveness of suicide prevention gatekeeper-training for university
      administrative staff in Japan.
AB  - AIMS: Suicide is a leading cause of death among Japanese college and university
      students. Gatekeeper-training programs have been shown to improve detection and
      referral of individuals who are at risk of suicide by training non-mental-health
      professional persons. However, no studies have investigated the effectiveness of
      such programs in university settings in Japan. The aim of this study was to
      investigate the effectiveness of the gatekeeper-training program for
      administrative staff in Japanese universities. METHODS: We developed a 2.5-h
      gatekeeper-training program based on the Mental Health First Aid program, which
      was originally developed for the general public. Seventy-six administrative staff
      at Hokkaido University participated in the program. Competence and confidence in
      managing suicide intervention, behavioral intention as a gatekeeper and attitude
      while handling suicidal students were measured by a self-reported questionnaire
      before, immediately after and a month after the program. RESULTS: We found a
      significant improvement in competence in the management of suicidal students. We
      also found improvements in confidence in management of suicidal students and
      behavioral intention as a gatekeeper after training, though questionnaires for
      those secondary outcomes were not validated. These improvements continued for a
      month. About 95% of the participants rated the program as useful or very useful
      and one-third of the participants had one or more chances to utilize their skills
      within a month. CONCLUSIONS: The current results suggest the positive effects of
      the training program in university settings in Japan. Future evaluation that
      includes comparison with standard didactic trainings and an assessment of long
      term effectiveness are warranted.

PMID- 26303331
TI  - Comparison of ambulatory blood pressure measurement with home, office and
      pharmacy measurements: is arterial blood pressure measured at pharmacy reliable?
AB  - RATIONALE, AIMS AND OBJECTIVES: Standardizing arterial blood pressure (BP)
      measurement is difficult because of different performers like doctor or pharmacy
      employee. We investigated the reliability between different BP measurement
      methods. METHODS: The study was conducted in an internal medicine service with
      160 patients in Ankara, Turkey. First, the subjects' BP was measured by doctor.
      Then, 24-hour BP monitoring devices were placed. Participants were then
      instructed to measure their BPs both at home and in pharmacy. The next day,
      arterial BP was measured by the doctor for the second time. RESULTS: The
      prevalence rates of masked and white coat hypertension were 8.8% (n = 14) and
      8.1% (n = 13), respectively. There was no statistically significant differences
      between ambulatory measurement and home, office and pharmacy measurements (P >
      0.05). The consistency rate between ambulatory and home measurements was 97.5%
      (kappa = 0.947, P < 0.001). The consistency rate between ambulatory and pharmacy
      measurements was 82.5% (kappa = 0.634, P < 0.001). When compared with ambulatory
      measurement, the most sensitive (98.0%) and most specific (96.8%) method was home
      measurement. There was a moderate positive correlation between ambulatory and
      other measurements in both systolic and diastolic values. There was a positive
      and very strong correlation between ambulatory and home measurements of systolic
      and diastolic ABP values (respectively; r = 0.926 and r = 0.968) and there was a
      statistically significant relation between these measurements (P < 0.001).
      CONCLUSION: The results of all measurement methods were close to each other. The
      most sensitive and specific method was home measurement when compared with
      ambulatory measurement. But both office and pharmacy measurements had also high
      sensitivity and specificity.

PMID- 26303332
TI  - Introduction to Special Issue on 'Nrf2 Regulated Redox Signaling and Metabolism
      in Physiology and Medicine.

PMID- 26303333
TI  - Arylhydrocarbon receptor-dependent mIndy (Slc13a5) induction as possible
      contributor to benzo[a]pyrene-induced lipid accumulation in hepatocytes.
AB  - Non-alcoholic fatty liver disease is a growing problem in industrialized and
      developing countries. Hepatic lipid accumulation is the result of an imbalance
      between fatty acid uptake, fatty acid de novo synthesis, beta-oxidation and
      secretion of triglyceride-rich lipoproteins from the hepatocyte. A central
      regulator of hepatic lipid metabolism is cytosolic citrate that can either be
      derived from the mitochondrium or be taken up from the blood via the plasma
      membrane sodium citrate transporter NaCT, the product of the mammalian INDY gene
      (SLC13A5). mINDY ablation protects against diet-induced steatosis whereas mINDY
      expression is increased in patients with hepatic steatosis. Diet-induced hepatic
      steatosis is also enhanced by activation of the arylhyrocarbon receptor (AhR)
      both in humans and animal models. Therefore, the hypothesis was tested whether
      the mINDY gene might be a target of the AhR. In accordance with such a
      hypothesis, the AhR activator benzo[a]pyrene induced the mINDY expression in
      primary cultures of rat hepatocytes in an AhR-dependent manner. This induction
      resulted in an increased citrate uptake and citrate incorporation into lipids
      which probably was further enhanced by the benzo[a]pyrene-dependent induction of
      key enzymes of fatty acid synthesis. A potential AhR binding site was identified
      in the mINDY promoter that appears to be conserved in the human promoter.
      Elimination or mutation of this site largely abolished the activation of the
      mINDY promoter by benzo[a]pyrene. This study thus identified the mINDY as an AhR
      target gene. AhR-dependent induction of the mINDY gene might contribute to the
      development of hepatic steatosis. 

PMID- 26303334
TI  - Alcohol use, socioeconomic deprivation and ethnicity in older people.
AB  - OBJECTIVES: This study explores the relationship between alcohol consumption,
      health, ethnicity and socioeconomic deprivation. PARTICIPANTS: 27,991 people aged
      65 and over from an inner-city population, using a primary care database. PRIMARY
      AND SECONDARY OUTCOME MEASURES: Primary outcome measures were alcohol use and
      misuse (>21 units per week for men and >14 for units per week women). RESULTS:
      Older people of black and minority ethnic (BME) origin from four distinct ethnic
      groups comprised 29% of the sample. A total of 9248 older drinkers were
      identified, of whom 1980 (21.4%) drank above safe limits. Compared with older
      drinkers, older unsafe drinkers contained a higher proportion of males, white and
      Irish ethnic groups and a lower proportion of Caribbean, African and Asian
      groups. For older drinkers, the strongest independent predictors of higher
      alcohol consumption were younger age, male gender and Irish ethnicity.
      Independent predictors of lower alcohol consumption were Asian, black Caribbean
      and black African ethnicity. Socioeconomic deprivation and comorbidity were not
      significant predictors of alcohol consumption in older drinkers. For older unsafe
      drinkers, the strongest predictor variables were younger age, male gender and
      Irish ethnicity; comorbidity was not a significant predictor. Lower socioeconomic
      deprivation was a significant predictor of unsafe consumption whereas African,
      Caribbean and Asian ethnicity were not. CONCLUSIONS: Although under-reporting in
      high-alcohol consumption groups and poor health in older people who have stopped
      or controlled their drinking may have limited the interpretation of our results,
      we suggest that closer attention is paid to 'young older' male drinkers, as well
      as to older drinkers born outside the UK and those with lower levels of
      socioeconomic deprivation who are drinking above safe limits.

PMID- 26303335
TI  - Exploring redundant research into the effect of tranexamic acid on surgical
      bleeding: further analysis of a systematic review of randomised controlled
      trials.
AB  - OBJECTIVES: We examined whether apparent redundancy in a cumulative meta-analysis
      of trials is justified by concern about bias, random error or generalisability of
      the results. DESIGN: Cumulative meta-analysis, risk of bias assessment, trial
      sequential analysis, description of study participants over time and a review of
      rationales for conducting trials. DATA SOURCE: 126 randomised trials included in
      a systematic review assessing of tranexamic acid on blood transfusion in surgery.
      RESULTS: The cumulative meta-analysis including all trials shows that the pooled
      estimate first reached statistical significance after the second trial in 1993.
      When the analysis was limited to the 38 high-quality trials and adjusted to
      account for potential systematic and random errors, the uncertainty was resolved
      after the 22nd trial in 2008. When the analysis was restricted to the two high
      quality, prospectively registered trials, the cumulative z-curve crossed p=0.05
      but not the monitoring boundary, suggesting an early potentially spurious
      statistically significant result. As precision of the pooled estimate increased,
      the number of trials initiated increased, although trial activity appeared to
      move to other surgery types. Most (62%) reports cited at least one systematic
      review. Of 118 reports examined, concern about generalisability was the reason
      for initiating the trial in 60%. Other reasons were to address a question other
      than the effect on bleeding (26%) and to confirm previously observed results
      (4%). Unawareness of previous research was apparent in 4% trials, while the
      rationale was unclear in 3%. CONCLUSIONS: Our results indicate that poor quality
      is a more important cause of redundant research than the failure to review
      existing evidence. Concerns about generalisability of results is the main
      motivation for new trials. Contrary to previous claims, our results suggest that
      systematic reviews showing treatment effects can stimulate an increase in trial
      activity rather than reduce it.

PMID- 26303336
TI  - Searching for the synergistic effect between aclidinium and formoterol: From
      bench to bedside.
AB  - Aim of our study was to understand if the interaction between aclidinium and
      formoterol administered at therapeutic doses leads to a synergistic rather than
      additive broncholytic effect. We tested the type of effect ex vivo on isolated
      human bronchi and then in vivo in COPD patients. The analysis of the interaction
      between aclidinium and formoterol in vitro was measured by applying the Unified
      Theory, whereas that in COPD patients was measured by applying the Bliss
      Independence criterion. Aclidinium and formoterol administered alone completely
      relaxed human isolated bronchial tissues sub-maximally pre-contracted with ACh in
      a concentration-dependent manner with similar potency (EC50: aclidinium 4.64 +/-
      0.78 nM, formoterol 2.71 +/- 0.21), whereas the interaction of aclidinium plus
      formoterol produced moderate to strong synergism. Changes in FEV1 values showed
      that inhaled aclidinium and formoterol induced a significant and time-dependent
      bronchodilatory effect during the study time. The inhalation of aclidinium and
      formoterol in combination significantly anticipated at 5 min post-administration
      the bronchodilatory effect of FEV1, compared with the effect of drugs
      administered alone. There was a synergistic interaction for FEV1 at 5 min and
      from 120 min to 240 min post-inhalation, whereas from 30 min to 60 min post
      administration the drug interaction was additive. This study shows that
      aclidinium and formoterol can produce a significant synergistic interaction that
      may have a role also in the clinic setting.

PMID- 26303337
TI  - Preoperative exercise therapy in lung surgery patients: A systematic review.
AB  - OBJECTIVES: The impact of postoperative complications after lung surgery for
      cancer is substantial, with the increasing age of patients and the presence of
      comorbidities. This systematic review summarises the effects of Preoperative
      Exercise Therapy (PET) in patients scheduled for lung surgery on aerobic
      capacity, physical fitness, postoperative complications, length of hospital stay,
      quality of life and recovery. METHODS: A systematic search on PET prior to lung
      surgery was conducted. The methodological quality of the included studies was
      rated using the Physiotherapy Evidence Database (PEDro) scale. The agreement
      between the reviewers was assessed with Cohen's kappa. RESULTS: A total of eleven
      studies were included with a methodological quality ranging from poor to good.
      The agreement between the reviewers, assessed with the Cohen's kappa, was 0.79.
      Due to substantial heterogeneity in the interventions across the included
      studies, it was impossible to conduct a meta-analysis. The most important finding
      of this systematic review was that PET based on moderate to intense exercise in
      patients scheduled for lung surgery has beneficial effects on aerobic capacity,
      physical fitness and quality of life. Also PET may reduce postoperative
      complications and length of hospital stay. CONCLUSION: PET may have beneficial
      effects on various physical fitness variables and postoperative complications in
      patients with lung cancer scheduled for surgery. Future research must focus on
      developing patient tailored exercise programs and investigate the influence of co
      existing comorbidities on the outcome measures. Definitions of PET, including
      timing, (acceptable) duration, intensity and exercise training methods should be
      determined and compared.

PMID- 26303338
TI  - Survival in interstitial pneumonia with features of autoimmune disease: a
      comparison of proposed criteria.
AB  - BACKGROUND: Some patients with chronic fibrosing interstitial pneumonia (IP) have
      clinical, serological, and morphological features suggestive of, but not
      diagnostic for, a connective tissue disease. Several names and diagnostic
      criteria for this entity have been proposed. The objective of this study was to
      compare the clinical characteristics and behavior of each of the proposed
      diagnostic criteria. METHODS: Patients with chronic fibrosing IP were identified
      from an ongoing, longitudinal cohort. Four published diagnostic criteria for what
      we generically label as "IP with features of autoimmunity" were applied to all
      patients to identify four unique cohorts (Kinder, Vij, Corte, and Fischer).
      Kaplan-Meier survival functions compared differences in survival in each cohort
      between patients meeting and not meeting criteria. Unadjusted and adjusted Cox
      proportional hazard regression models identified predictors of survival. RESULTS:
      The study cohort included 119 patients, 40% of whom were female. The mean age was
      65.5 years. There was overlap between the four different criteria, identifying
      patients with similar clinical characteristics. Interstitial pneumonia patients
      with features of autoimmunity tended to have improved survival compared to those
      without these features (p-value range 0.03-0.10) on univariate analysis. After
      adjusting for disease severity using the gender-age-physiology score, only the
      Corte criteria was an independent predictor of survival (p-value 0.04).
      CONCLUSION: Interstitial pneumonia with features of autoimmunity may be
      associated with improved survival compared to those patients without these
      features depending on which criteria is used to define the population. These data
      support the efforts being made to standardize the definition.

PMID- 26303339
TI  - Reproducibility of the bronchoconstrictive response to eucapnic voluntary
      hyperpnoea.
AB  - BACKGROUND: Eucapnic voluntary hyperpnoea (EVH) is considered an effective
      bronchoprovocation challenge for identifying exercise-induced bronchoconstriction
      (EIB). However, the reproducibility of the hyperpnoea-induced bronchoconstriction
      (HIB) response elicited by EVH remains unknown and was therefore the focus of
      this study. METHODS: Two cohorts of 16 physically active males (each cohort
      comprised 8 controls and 8 with physician diagnosis of asthma) participated in
      two studies of the short- and long-term reproducibility of the
      bronchoconstrictive response to an EVH test with dry air. EVH was performed on
      days 0, 7, 14, and 21 (short-term study), and 0, 35, and 70 (long-term study).
      HIB was diagnosed by a >=10% fall in forced expiratory volume in 1 s (FEV1) after
      EVH. RESULTS: On day 0 of the short-term study, FEV1 fell by 2 +/- 1% (P < 0.05)
      and 27 +/- 18% (P < 0.01) from pre-to post-EVH in control and HIB-positive groups
      respectively. The post-EVH fall in FEV1 did not differ across the short-term
      study test days. In the HIB-positive group, the day-to-day coefficient of
      variation, reproducibility, and smallest meaningful change for the fall in FEV1
      were 12%, 328 mL, and 164 mL, respectively. On day 0 of the long-term study, FEV1
      fell by 2 +/- 2% and 25 +/- 18% (P < 0.01) after EVH in control and HIB-positive
      groups respectively. The post-EVH fall in FEV1 did not differ across the long
      term study test days. In the HIB-positive group, the day-to-day coefficient of
      variation, reproducibility, and smallest meaningful change for the fall in FEV1
      were 10%, 196 mL, and 98 mL respectively. CONCLUSION: The EVH test elicits a
      reproducible bronchoconstrictive response in physically active males with
      physician diagnosed asthma. These data thus support the clinical utility of the
      EVH test for EIB screening and monitoring.

PMID- 26303340
TI  - Adenosine A2A receptors permit mGluR5-evoked tyrosine phosphorylation of NR2B
      (Tyr1472) in rat hippocampus: a possible key mechanism in NMDA receptor
      modulation.
AB  - A great body of evidence points toward a functional interaction between
      metabotropic glutamate 5 receptors (mGluR5) and NMDA receptors (NMDAR) that
      enhances synaptic plasticity and cognition. However, the molecular mechanism
      underlying this interaction remains unclear. Here, we show that co-activation of
      mGluR5 and NMDAR in hippocampal slices synergistically leads to a robust
      phosphorylation of NR2B (Tyr1472), which is Src kinase dependent and is enabled
      by endogenous adenosine acting on A2A receptors. As it is well known, NR2B
      (Tyr1472) phosphorylation anchors NR2B-containing NMDARs to the surface of post
      synaptic membranes, preventing their internalization. This is supported by our
      electrophysiological experiments showing that co-activation of mGluR5 and NMDARs
      robustly enhances NMDAR-dependent neuronal excitability recorded in CA1
      hippocampal region, which temporally coincides with the robust increase in NR2B
      (Tyr1472) phosphorylation, depends on Src kinases and is also permitted by A2A
      receptors. Thus, we strongly suggest that NR2B (Tyr1472) phosphorylation
      constitutes, at least to some extent, the molecular mechanism underlying the
      mGluR5-mediated enhancement of NMDAR-dependent responses, which is modulated by
      A2A receptors. A better understanding of the molecular basis of mGluR5/NMDAR
      interaction would elucidate their role in synaptic plasticity processes as well
      as in pathological conditions. We propose the following molecular mechanism by
      which metabotropic Glutamate Receptor 5 (mGluR5) potentiate ionotropic Glutamate
      N-Methyl-D-Aspartate Receptor (NMDAR) responses in rat hippocampus. Co-activation
      of mGLUR5/NMDAR activates Src kinases, leading to NR2B(Tyr1472) phosphorylation,
      which anchors NR2B-containing NMDAR to the plasma membrane, thus inducing a
      robust increase in the NMDA-dependent excitability. Interestingly, adenosine A2A
      receptors license the mGluR5-induced NR2B(Tyr1472) phosphorylation.

PMID- 26303341
TI  - Lidocaine for Status Epilepticus in Pediatrics.
AB  - BACKGROUND: Our goal was to perform a systematic review of the literature on the
      use of intravenous lidocaine in pediatrics for status epilepticus (SE) and
      refractory status epilepticus (RSE) to determine its impact on seizure control.
      METHODS: All articles from MEDLINE, BIOSIS, EMBASE, Global Health, HealthStar,
      Scopus, Cochrane Library, the International Clinical Trials Registry Platform
      (inception to November 2014), and gray literature were searched. The strength of
      evidence was adjudicated using both the Oxford and Grading of Recommendations
      Assessment, Development, and Evaluation methodologies by two independent
      reviewers. RESULTS: Overall, 20 original studies were identified, with 19
      manuscripts and one meeting abstract. Two hundred and thirty-five pediatric
      patients were treated for 252 episodes of SE/RSE. Patients had varying numbers of
      antiepileptic drugs (two to eight) on board before lidocaine therapy. During 20
      of the 252 (7.9%) episodes of SE/RSE, phenytoin was on board. The dose regimen of
      lidocaine varied, with some using bolus dosing alone; others used a combination
      of bolus and infusion therapy. Overall, 60.0% of seizures responded to lidocaine,
      with complete cessation and greater than 50% reduction seen in 57.6% and 12.3%,
      respectively. Patient outcomes were sparingly reported. CONCLUSIONS: There
      currently exists Oxford level 2b, Grading of Recommendations Assessment
      Development, and Evaluation C evidence to support the consideration of lidocaine
      for SE and RSE in the pediatric population. Further prospective studies of
      lidocaine administration in this setting are warranted.

PMID- 26303342
TI  - Flexible metabolic pathway construction using modular and divisible selection
      gene regulators.
AB  - Genetic selections are important to biological engineering. Although selectable
      traits are limited, currently each trait only permits simultaneous introduction
      of a single DNA fragment. Complex pathway and strain construction however depends
      on rapid, combinatorial introduction of many genes that encode putative pathway
      candidates and homologs. To triple the utility of existing selection genes, we
      have developed divisible selection in Saccharomyces cerevisiae. Here, independent
      DNA fragments can be introduced and selected for simultaneously using a set of
      split hybrid transcription factors composed of parts from Escherichia coli LexA
      and Herpes simplex VP16 to regulate one single selectable phenotype of choice.
      Only when co-expressed, these split hybrid transcription factors promote
      transcription of a selection gene, causing tight selection of transformants
      containing all desired DNA fragments. Upon transformation, 94% of the selected
      colonies resulted strictly from transforming all three modules based on ARS/CEN
      plasmids. Similarly when used for chromosome integration, 95% of the
      transformants contained all three modules. The divisible selection system acts
      dominantly and thus expands selection gene utility from one to three without any
      genomic pre-modifications of the strain. We demonstrate the approach by
      introducing the fungal rubrofusarin polyketide pathway at a gene load of 11 kb
      distributed on three different plasmids, using a single selection trait and one
      yeast transformation step. By tripling the utility of existing selection genes,
      the employment of divisible selection improves flexibility and freedom in the
      strain engineering process.

PMID- 26303343
TI  - Plerixafor (Mozobil): A Stem Cell-Mobilizing Agent for Transplantation in
      Lymphoma Patients Predicted to Be Poor Mobilizers - A Pilot Study.
AB  - Autologous hematopoietic stem cell transplantation is the standard therapy for
      refractory/relapsed aggressive lymphoma. The initial step of the procedure
      involves mobilization and collection of hematopoietic stem cells. G-CSF fails to
      achieve mobilization in 15-25% of lymphoma patients. Plerixafor is a novel CXCR4
      antagonist that can promote mobilization. It has been used successfully in
      patients after the failure of G-CSF. It is reasonable to test whether plerixafor
      should become the mobilizing agent of choice in patients expected to exhibit
      difficulties in mobilization. We initiated a study to assess the use of
      plerixafor as a first-line stem cell mobilizer in 20 elderly or heavily
      pretreated patients with non-Hodgkin or Hodgkin lymphoma. The minimum defined
      CD34+ cell dose of >=2 * 106 cells/kg was achieved by 90% of the patients, and
      for 83% of them with one apheresis procedure. The target CD34+ dose of >=5 * 106
      cells/kg was achieved by 70% of the patients. The median number of circulating
      CD34+ cells before and after plerixafor was 14.4 and 42.8 cells/MUl,
      respectively. The post-plerixafor adverse events were mild. All patients promptly
      engrafted after high-dose chemotherapy treatment. We conclude that plerixafor
      administration is safe and efficient for upfront mobilization in lymphoma
      patients predicted to be poor mobilizers. 

PMID- 26303344
TI  - Flagellin suppresses experimental asthma by generating regulatory dendritic cells
      and T cells.
AB  - BACKGROUND: Although the hygiene hypothesis suggests that microbial infections
      could subvert asthma and thus a microbial product might serve as a therapeutic
      adjuvant for asthma, the relationship between bacterial components and asthma is
      complex. Recently, low levels of flagellin, the Toll-like receptor (TLR) 5
      ligand, have been reported to promote asthma. OBJECTIVE: We show that a
      therapeutic dose of flagellin suppresses asthma and that the effect occurs
      through generating regulatory dendritic cells (rDCs) and regulatory T (Treg)
      cells. METHODS: Ovalbumin (OVA)-induced wild-type and TLR5 knockout asthmatic
      mice were treated intranasally with a mixture of OVA and 10 MUg of a flagellin B
      (FlaB; of Vibrio vulnificus). OVA/FlaB-treated rDCs were adoptively transferred
      to mice with OVA-induced asthma. Anti-CD25 mAb was used to deplete Treg cells. A
      mixture of house dust mite (HDM) and FlaB was used to treat mice with HDM-induced
      asthma. Blood CD14(+) monocyte-derived dendritic cells from HDM-sensitive
      asthmatic patients were treated with FlaB and incubated with autologous CD4(+) T
      cells. RESULTS: An OVA/FlaB mixture ameliorated OVA-induced asthma by inhibiting
      TH1/TH2/TH17 responses in a TLR5-dependent manner through generating rDCs and
      Treg cells. The adoptive transfer of OVA/FlaB-treated dendritic cells inhibited
      OVA-induced asthma, whereas the depletion of CD25(+) cells eliminated the
      inhibitory effect. A similar effect of FlaB was observed in mice with HDM-induced
      asthma. In patients with HDM-sensitive asthma, FlaB-treated rDCs inhibited HDM
      stimulated TH1/TH2 responses while enhancing Treg cells in an IL-10-dependent
      manner. CONCLUSION: These findings collectively suggest that flagellin could be
      used as a tolerogenic adjuvant to treat allergic asthma.

PMID- 26303345
TI  - Coffee and Depression: A Short Review of Literature.
AB  - Coffee is among the most widespread and healthiest beverages in the world. It is
      known to be a highly rich source of biologically active natural metabolites which
      possess therapeutic effects (i.e. caffeine) and functional properties (i.e.
      chlorogenic acids). Therefore, coffee can be considered a drink which has
      different positive effects on human health such as cardioprotective,
      neuroprotective, hepatoprotective, nephroprotective, etc. However, heavy coffee
      consumption may be related to some unpleasant symptoms, mainly anxiety, headache,
      increased blood pressure, nausea, and restlessness. During the past two decades,
      several studies have indicated that there is a close correlation between
      consumption of coffee and incidence of depression. In addition, phytochemical
      studies showed that caffeine is the main responsible constituent for
      antidepressant effects of coffee through multiple molecular mechanisms. The aim
      of the present paper was to collect the latest literature data (from 1984 to
      2014) on the positive and negative impacts of coffee consumption on the major
      depressive disorders and to clarify the role of bioactive constituents of coffee
      in the related different clinical trials. To the best of our knowledge, this the
      first review on this topic. 

PMID- 26303346
TI  - Widowhood and the Stability of Late Life Depressive Symptomatology in the Swedish
      Adoption Twin Study of Aging.
AB  - Although the Swedish Adoption Twin of Aging (SATSA) has been used to investigate
      phenotypic stability of late life depressive symptoms, the biometric processes
      underlying this stability have not been studied. Under a reciprocal effects
      modeling framework, we used SATSA twins' Center for Epidemiologic Studies
      Depression (CES-D) Scale data across 5 waves (from 1987-2007) to test whether the
      reciprocal exchange between twins within a family and their nonshared
      environments (P<=>E) promote the accumulation of gene-environment correlation
      (rGE) over time. The model generates increasing rGE that produces subsequent
      stable environmental differences between twins within a family-a process
      hypothesized to explain stability in chronic late life depressive symptoms.
      Widowhood is included as a stressful life experience that may introduce an
      additional nonshared source of variability in CES-D scores. Genetic effects and
      nonshared environmental effects are primary sources of stability of late life
      depressive symptoms without evidence of underlying rGE processes. Additionally,
      widowhood explained stable differences in CES-D scores between twins within a
      family up to 3 years after spousal loss. 

PMID- 26303347
TI  - An Interactive Computer Session to Initiate Physical Activity in Sedentary
      Cardiac Patients: Randomized Controlled Trial.
AB  - BACKGROUND: Physical activity (PA) improves many facets of health. Despite this,
      the majority of American adults are insufficiently active. Adults who visit a
      physician complaining of chest pain and related cardiovascular symptoms are often
      referred for further testing. However, when this testing does not reveal an
      underlying disease or pathology, patients typically receive no additional
      standard care services. A PA intervention delivered within the clinic setting may
      be an effective strategy for improving the health of this population at a time
      when they may be motivated to take preventive action. OBJECTIVE: Our aim was to
      determine the effectiveness of a tailored, computer-based, interactive personal
      action planning session to initiate PA among a group of sedentary cardiac
      patients following exercise treadmill testing (ETT). METHODS: This study was part
      of a larger 2x2 randomized controlled trial to determine the impact of
      environmental and social-cognitive intervention approaches on the initiation and
      maintenance of weekly PA for patients post ETT. Participants who were referred to
      an ETT center but had a negative-test (ie, stress tests results indicated no
      apparent cardiac issues) were randomized to one of four treatment arms: (1)
      increased environmental accessibility to PA resources via the provision of a free
      voucher to a fitness facility in close proximity to their home or workplace
      (ENV), (2) a tailored social cognitive intervention (SC) using a "5 As"-based
      (ask, advise, assess, assist, and arrange) personal action planning tool, (3)
      combined intervention of both ENV and SC approaches (COMBO), or (4) a matched
      contact nutrition control (CON). Each intervention was delivered using a computer
      based interactive session. A general linear model for repeated measures was
      conducted with change in PA behavior from baseline to 1-month post interactive
      computer session as the primary outcome. RESULTS: Sedentary participants (n=452;
      34.7% participation rate) without a gym membership (mean age 58.57 years; 59%
      female, 78% white, 12% black, 11% Hispanic) completed a baseline assessment and
      an interactive computer session. PA increased across the study sample
      (F1,441=30.03, P<.001). However, a time by condition interaction (F3,441=8.33,
      P<.001) followed by post hoc analyses indicated that SC participants exhibited a
      significant increase in weekly PA participation (mean 45.1, SD 10.2) compared to
      CON (mean -2.5, SD 10.8, P=.004) and ENV (mean 8.3, SD 8.1, P<.05). Additionally,
      COMBO participants exhibited a significant increase in weekly PA participation
      (mean 53.4, SD 8.9) compared to CON (P<.001) and ENV (P=.003) participants. There
      were no significant differences between ENV and CON or between SC and COMBO.
      CONCLUSIONS: A brief, computer-based, interactive personal action planning
      session may be an effective tool to initiate PA within a health care setting, in
      particular as part of the ETT system. TRIAL REGISTRATION: Clinicaltrials.gov
      NCT00432133, http://clinicaltrials.gov/ct2/show/NCT00432133 (Archived by WebCite
      at http://www.webcitation.org/6aa8X3mw1).

PMID- 26303348
TI  - Pro-inflammatory obesity in aged cannabinoid-2 receptor-deficient mice.
AB  - BACKGROUND AND OBJECTIVES: Cannabinoid-1 receptor signaling increases the
      rewarding effects of food intake and promotes the growth of adipocytes, whereas
      cannabinoid-2 receptor (CB2) possibly opposes these pro-obesity effects by
      silencing the activated immune cells that are key drivers of the metabolic
      syndrome. Pro- and anti-orexigenic cannabimimetic signaling may become unbalanced
      with age because of alterations of the immune and endocannabinoid system.
      METHODS: To specifically address the role of CB2 for age-associated obesity, we
      analyzed metabolic, cardiovascular, immune and neuronal functions in 1.2-1.8-year
      old CB2(-/-) and control mice, fed with a standard diet and assessed effects of
      the CB2 agonist, HU308, during high-fat diet (HFD) in 12-16-week-old mice.
      RESULTS: The CB2(-/-) mice were obese with hypertrophy of visceral fat, immune
      cell polarization toward pro-inflammatory subpopulations in fat and liver and
      hypertension, as well as increased mortality despite normal blood glucose. They
      also developed stronger paw inflammation and a premature loss of transient
      receptor potential responsiveness in primary sensory neurons, a phenomenon
      typical for small fiber disease. The CB2 agonist HU308 prevented HFD-evoked
      hypertension, reduced HFD-evoked polarization of adipose tissue macrophages
      toward the M1-like pro-inflammatory type and reduced HFD-evoked nociceptive
      hypersensitivity, but had no effect on weight gain. CONCLUSIONS: CB2 agonists may
      fortify CB2-mediated anti-obesity signaling without the risk of anti-CB1-mediated
      depression that caused the failure of rimonabant.

PMID- 26303349
TI  - Cross-sectional and prospective associations between moderate to vigorous
      physical activity and sedentary time with adiposity in children.
AB  - BACKGROUND: Physical activity (PA) and sedentary time (SED) have both been
      suggested as potential risk factors for adiposity in children. However, there is
      paucity of data examining the temporal associations between these variables.
      OBJECTIVE: This study aimed to analyze the cross-sectional and prospective
      associations between PA, SED and body composition in children. METHODS: A total
      of 510 children (age at baseline 10.1+/-0.8, age at follow-up 11.8+/-0.9) from
      six Portuguese schools from the Oeiras Municipality participated in this study.
      PA and SED were measured by accelerometry and trunk fat mass (TFM) and body fat
      mass (BFM) were measured by dual energy X-ray absorptiometry. Fat mass index
      (FMI) was calculated as BFM divided by height squared. Several regression models
      adjusted for age, sex, maturity status, follow-up duration, baseline levels of
      the outcome variable and SED or moderate to vigorous PA (MVPA) were performed.
      RESULTS: MVPA (min per day) was cross-sectionally inversely associated with
      adiposity indexes (FMI, TFM and BFM). Adiposity indexes were inversely associated
      with time in MVPA. In prospective analyses, MVPA was associated with a lower
      levels of FMI (beta=-0.37, 95% confidence interval (CI): -0.49 to -0.26,
      P<0.001), TFM (beta=-0.20, 95% CI: -0.29 to -0.10, P<0.001) and BFM (beta=-0.37,
      95% CI: -0.49 to -0.26, P<0.001). When the model was adjusted for age, sex,
      maturity status and for baseline levels of the outcome variables MVPA remained a
      significant predictor of lower adiposity indexes (FMI: beta=-0.09, 95% CI: -0.16
      to -0.01, P<0.05; TFM: beta=-0.08, 95% CI: -0.15 to -0.01, P<0.05; BFM: beta=
      0.07, 95% CI: -0.15 to 0.00, P<0.05). Adiposity was not associated with MVPA when
      modeled as the exposure in prospective analyses. SED was not related with
      adiposity indexes, except for the relationship with FMI. CONCLUSIONS: In cross
      sectional and prospective analyses, MVPA is associated with lower adiposity
      independent of covariates and SED. Results suggest that promoting MVPA is
      important for preventing gain in adiposity in healthy children.

PMID- 26303350
TI  - Helpful or harmful? Prospective association between weight misperception and
      weight gain among overweight and obese adolescents and young adults.
AB  - BACKGROUND/OBJECTIVE: Weight misperception is common among adolescents with
      obesity, but it is not known whether weight perception is related to future
      weight gain. The objective of the study was to examine the prospective
      association between accurate weight perception versus weight misperception and
      weight change among youth who are overweight or obese. SUBJECTS/METHODS: Using a
      subsample of The National Longitudinal Study of Adolescent to Adult Health Wave
      II cohort, we used linear regression modeling (adjusted for age, baseline body
      mass index (BMI), parental education, household percent federal poverty level,
      depression, race and ethnicity) to examine the prospective association between
      weight misperception (that is, perceiving oneself to be under or normal weight)
      among 2738 overweight and obese youth and subsequent BMI change from Wave II
      (1996) to Wave IV (2008-2009). Mean age at baseline (Wave II) was 15.9 (0.1).
      RESULTS: Fifty-seven percent of males and 80% of females accurately perceived
      themselves as overweight. In fully adjusted models, weight misperception was
      associated with less BMI gain among youth who were overweight and obese.
      Specifically, youth who perceived themselves to be at a healthy weight had lower
      BMI gains (males: beta= -1.43, 95% confidence interval (CI)=(-2.26, -0.60),
      P=0.001; females: beta= -1.35, 95% CI=(-2.59, -0.11), P=0.035) from Wave II to IV
      relative to those who accurately perceived themselves as overweight or obese.
      CONCLUSIONS: Contrary to commonly held assumptions, weight misperception among a
      non-clinical sample of youth who were overweight or obese predicted lower future
      weight gain. Efficacy of efforts to correct weight misperception should be
      rigorously examined to assess for both intended and unintended consequences.

PMID- 26303351
TI  - Adenovirus 36 infection: a role in dietary intake and response to inpatient
      weight management in obese girls.
AB  - Human adenovirus 36 (Adv36) increases adiposity and is more prevalent in
      overweight and obese children. Dietary intake in animal models is comparable
      regardless of Adv36 status. The effects of Adv36 on obesity treatment outcomes
      have not been clarified. The aim of this study is to investigate the pre
      treatment dietary intake and the response to a 4-week inpatient weight management
      in 184 obese adolescent girls aged 13.0-17.9 years with respect to the presence
      of Adv36 antibodies. Evaluation of 3-day dietary records did not show any
      difference in daily intake of energy and essential nutrients between Adv36
      antibody positive and negative girls. After the intervention Adv36 positive girls
      presented with significantly greater decrease of waist circumference (P=0.020), z
      score of waist circumference (P=0.024), waist-to-hip ratio (P=0.007) and weight
      to-height ratio (P=0.019) compared with Adv36 negative girls. On the contrary,
      the sum of four skinfolds decreased significantly more in Adv36 negative than in
      Adv36 positive individuals (P=0.013). Neither body fat percentage nor metabolic
      and hormonal parameters showed any significant relevance to Adv36 status in
      response to weight loss intervention. In conclusion, energy restriction in Adv36
      antibody positive girls was associated with greater decrease of abdominal obesity
      and preservation of subcutaneous fat tissue than in those antibody negative. 

PMID- 26303353
TI  - Does miRNA-155 Promote Cyclooxygenase-2 Expression in Cancer?
AB  - Preclinical Research MicroRNA (miR)-155 and cyclooxygenase (COX)-2 are both
      elevated in numerous cancers including colorectal cancer. MiR-155 enhances COX-2
      expression and is an established regulator of epithelial-mesenchymal transition
      and inflammation. Inhibition of miR-155 or COX-2 exhibit similar negative effects
      on tumorigenicity. Thus, it is hypothesized that miR-155 may be a promising
      target for antagonizing COX-2 expression in colorectal and other cancers.

PMID- 26303352
TI  - Effects of RYGB on energy expenditure, appetite and glycaemic control: a
      randomized controlled clinical trial.
AB  - OBJECTIVES: Increased energy expenditure (EE) has been proposed as an important
      mechanism for weight loss following Roux-en-Y gastric bypass (RYGB). However,
      this has never been investigated in a controlled setting independent of changes
      in energy balance. Similarly, only few studies have investigated the effect of
      RYGB on glycaemic control per se. Here, we investigated the effect of RYGB on EE,
      appetite, glycaemic control and specific signalling molecules compared with a
      control group in comparable negative energy balance. SUBJECTS/METHODS: Obese
      normal glucose-tolerant participants were randomized to receive RYGB after 8
      (n=14) or 12 weeks (n=14). The protocol included a visit at week 0 and three
      visits (weeks 7, 11 and 78) where 24-h EE, appetite and blood parameters were
      assessed. Participants followed a low-calorie diet from weeks 0-11, with those
      operated at week 12 serving as a control group for those operated at week 8.
      RESULTS: Compared with controls, RYGB-operated participants had lower body
      composition-adjusted 24-h EE and basal EE 3 weeks postoperatively (both P<0.05)
      but EE parameters at week 78 were not different from preoperative values (week
      7). Surgery changed the postprandial response of glucagon-like peptide-1 (GLP-1),
      peptide YY3-36 (PYY), ghrelin, cholecystokinin, fibroblast growth factor-19 and
      bile acids (all P<0.05). Particularly, increases in GLP-1, PYY and decreases in
      ghrelin were associated with decreased appetite. None of HOMA-IR (homeostasis
      model assessment-estimated insulin resistance), Matsuda index, the insulinogenic
      index, the disposition index and fasting hepatic insulin clearance were different
      between the groups, but RYGB operated had lower fasting glucose (P<0.05) and the
      postprandial glucose profile was shifted to the left (P<0.01). CONCLUSIONS: Our
      data do not support that EE is increased after RYGB. More likely, RYGB promotes
      weight loss by reducing appetite, partly mediated by changes in gastrointestinal
      hormone secretion. Furthermore, we found that the early changes in glycaemic
      control after RYGB is to a large extent mediated by caloric restriction.

PMID- 26303354
TI  - Effects of Dietary Contamination by Zearalenone and Its Metabolites on Serum Anti
      Mullerian Hormone: Impact on the Reproductive Performance of Breeding Cows.
AB  - We investigated the effects of in vivo exposure to low zearalenone levels on the
      anti-Mullerian hormone endocrine levels and the reproductive performance of
      cattle. Urine and blood samples and reproductive records were collected from two
      Japanese Black breeding female cattle herds with dietary zearalenone
      contamination below the threshold levels (<1 ppm) at 30 days after calving.
      Urinary zearalenone, alpha-zearalenol and beta-zearalenol concentrations were
      measured by chromatography-tandem mass spectrometry, and serum anti-Mullerian
      hormone concentrations were determined along with serum biochemical parameters.
      Urinary concentrations of alpha-zearalenol were significantly higher (p < 0.05)
      in cattle in Herd 1 than in cattle in Herd 2, reflecting the different amounts of
      zearalenone in the diet of the two herds. Although the number of 5-mm and 10-mm
      follicles of the herds and their fertility after artificial insemination were
      similar, the serum anti-Mullerian hormone concentrations in herds 1 and 2 were
      438.9 +/- 48.6 pg/ml and 618.9 +/- 80.0 pg/ml, respectively, with a trend towards
      a significant difference (p = 0.053), which may indicate differences in the
      antral follicle populations between herds. Thus, zearalenone intake from dietary
      feed, even when below the threshold zearalenone contamination level permitted in
      Japan, may affect the ovarian antral follicle populations, but not the fertility,
      of post-partum cows.

PMID- 26303355
TI  - Coronary artery disease. Complete revascularization in patients with multivessel
      disease.

PMID- 26303356
TI  - Risk factors: CVD risk and the 'obesity paradox'.

PMID- 26303357
TI  - Pharmacotherapy. Benefit of testosterone replacement therapy on CVD and
      mortality.

PMID- 26303358
TI  - Establishing a Clinical Competencies Committee.

PMID- 26303359
TI  - A Designated "Teaching Resident": A Novel Leadership Position to Promote
      Educational Skills and an Academic Career.

PMID- 26303360
TI  - Moreton Lecture: Imaging in the Age of Precision Medicine.
AB  - The term "precision medicine" (also known as "personalized medicine") is broadly
      defined as the tailoring of medical treatment to the individual characteristics
      of each patient. This process entails classifying patients into subpopulations
      that differ in their susceptibility to a particular disease, in the biology
      and/or prognosis of those diseases they may develop, or in their response to a
      specific treatment. Subpopulations are defined through systematic analysis and
      classification of patients' genotypic and phenotypic characteristics. Image
      findings are surrogates for phenotype manifestation of disease, and radiology
      reports are written descriptions of imaging phenotypes. Imaging phenotypes are
      often presented as classification, grading, or scoring systems that help assign
      patients to subpopulations for selecting treatment or assessing prognosis. The
      "spot sign score" that reflects the severity of bleeding in intracerebral
      hemorrhage is an example that has been used as an inclusion criterion in clinical
      trials. The term "radiogenomics" is used to describe the study of linkage between
      a patient's genotype and imaging phenotype. When a patient's genotype is known,
      it often suggests a surveillance role for imaging to determine clinical
      occurrence, location, extent, and severity of the associated disease; for
      example, use of breast imaging for enhanced surveillance in women known to harbor
      the BRCA1 and BRCA2 genes. Imaging is poised to play major roles in the age of
      precision medicine. The imaging community needs to learn new terminology and
      think in terms of how imaging phenotypes and imaging surveillance of patients
      with known genetic mutations can contribute to the concept. 

PMID- 26303361
TI  - De-Adoption and Un-Diffusion.

PMID- 26303362
TI  - Worried About us: Evaluating an Intervention for Relationship-Based Anxiety.
AB  - Although romantic relationships are commonly a source of pleasure and comfort,
      for some individuals they can be a source of persistent anxiety. The aim of the
      current investigation was to explore the construct of relationship-based anxiety
      and to evaluate the effectiveness of a brief couple-based psychoeducational
      session for this issue. Common behavioral patterns and cognitive tendencies seen
      among individuals with relationship-based anxiety were examined, including
      excessive reassurance-seeking, self-silencing, and partner accommodation. In the
      current investigation, a single psychoeducational session was developed to
      address these maladaptive interactive patterns of behavior specifically. The
      session was administered to a sample of 21 couples and was found to decrease
      levels of reassurance-seeking and self-silencing significantly among individuals
      with relationship anxiety, and to decrease levels of maladaptive accommodation
      behaviors significantly in their partners.

PMID- 26303363
TI  - Empty pericarp7 encodes a mitochondrial E-subgroup pentatricopeptide repeat
      protein that is required for ccmFN editing, mitochondrial function and seed
      development in maize.
AB  - RNA editing, converting cytidines (C) to uridines (U) at specific sites in the
      transcripts of mitochondria and plastids, plays a critical role in organelle gene
      expression in land plants. Recently pentatricopeptide repeat (PPR) proteins were
      identified as site-specific recognition factors for RNA editing. In this study,
      we characterized an empty pericarp7 mutant (emp7) in Zea mays (maize), which
      confers an embryo-lethal phenotype. In emp7 mutants, mitochondrial functions are
      seriously perturbed, resulting in a strikingly reduced respiration rate. Emp7
      encodes an E-subgroup PPR protein that is localized exclusively in the
      mitochondrion. Null mutation of Emp7 abolishes the C -> U editing of ccmF(N)
      transcript solely at position 1553. CcmF(N) is coding for a subunit of heme lyase
      complex in the cytochrome c maturation pathway. The resulting Phe -> Ser
      substitution in CcmF(N) leads to the loss of CcmF(N) protein and a strikingly
      reduced c-type cytochrome. Consequently, the mitochondrial cytochrome-linked
      respiratory chain is impaired as a result of the disassembly of complex III in
      the emp7 mutant. These results indicate that the PPR-E subgroup protein EMP7 is
      required for C -> U editing of ccmF(N) -1553 at a position essential for
      cytochrome c maturation and mitochondrial oxidative phosphorylation, and hence is
      essential to embryo and endosperm development in maize.

PMID- 26303365
TI  - Replication in physiotherapy: useful or reinventing the wheel?

PMID- 26303364
TI  - Dissociation of amyloid biomarkers in PET and CSF in Alzheimer's disease: a case
      report.
AB  - BACKGROUND: Recently, biomarkers have been suggested to be incorporated into
      diagnostic criteria for Alzheimer's disease (AD). Regarding disease-specific
      brain amyloid-beta deposition these comprise low amyloid-beta 1-42 in
      cerebrospinal fluid (CSF) and positive positron emission tomography (PET) amyloid
      imaging, while neuronal degeneration is evidenced by high total and
      phosphorylated tau levels in CSF (t-/p-tau), regional hypometabolism
      ([(18)F]fluorodeoxyglucose PET, FDG-PET) and characteristic atrophy-patterns
      (magnetic resonance imaging, MRI). CASE PRESENTATION: Here we present a case of
      clinically and biomarker supported AD (CSF t-/p-tau, MRI, FDG-PET) in a 59-year
      old Caucasian man in whom indicators of amyloid-beta deposition dissociated
      between CSF parameters and the respective PET imaging. CONCLUSIONS: Such cases
      highlight the necessity to better understand potential dissociations between PET
      and CSF data for amyloid-beta biomarkers, because they are currently considered
      interchangeably valid with regard to in-vivo evidence for AD pathology. This is
      more important since amyloid deposition markers can be considered a very first
      prognostic indicator of imminent AD, prior to neurodegenerative biomarkers and
      cognitive symptoms. The case illustrates the need for further longitudinal data
      on potential dissociations of AD biomarkers to devise recommendations for their
      better prognostic and diagnostic interpretation in the future.

PMID- 26303366
TI  - The Brief Pain Inventory (BPI).

PMID- 26303368
TI  - Daily movement patterns and predicted 10-yr risk for a first atherosclerotic
      cardiovascular disease (ASCVD) event using the pooled cohort risk equations among
      US adults.
AB  - OBJECTIVE: Examine the association between movement patterns and predicted risk
      of a first atherosclerotic cardiovascular disease (ASCVD) event. METHODS: Data
      from the 2003-2006 National Health and Nutrition Examination Survey (NHANES) were
      used (40-79 yrs; N=2421). Participants wore an ActiGraph 7164 accelerometer to
      create four movement pattern groups; Group 1: >=150 min/wk of moderate-to
      vigorous physical activity (MVPA) and light-intensity physical activity (LIPA) >=
      sedentary behavior (SB); Group 2: >=150 min/wk of MVPA and LIPA<SB; Group 3: <150
      min/wk of MVPA and LIPA>=SED; and Group 4: <150 min/wk of MVPA and LIPA<SB. 10-yr
      risk for a first ASCVD event was estimated using the pooled cohort equations.
      RESULTS: After adjusting for age, gender, race-ethnicity and obesity, Group 2
      (beta=-0.28; p=0.44) was not significantly different than Group 1, but Groups 3
      (beta=1.09; p=0.01) and 4 (beta=1.44; p<0.001) had a higher pooled risk score.
      CONCLUSIONS: Those in the least desirable movement pattern (Group 4) had the
      highest pooled risk score. Given the similar risk scores for Groups 1 and 2,
      future research is needed to determine if sufficient MVPA can counteract the
      potential consequences associated with an imbalanced LIPA:SB ratio (i.e.,
      LIPA<SB).

PMID- 26303367
TI  - Engagement and experience with cancer-related follow-up care among young adult
      survivors of childhood cancer after transfer to adult care.
AB  - PURPOSE: Young adult survivors (YAS) of childhood cancer require annual adult
      focused, cancer-related follow-up given their risk for late effects of treatment.
      This study describes perception of and engagement with adult-focused, cancer
      related follow-up care and general health care among YAS formally transferred to
      adult care from pediatric survivorship care. METHODS: YAS transferred from
      pediatric survivorship care in the prior 1-5 years completed measures indicating
      engagement with cancer-related follow-up care, other health care utilization,
      content of communication by providers, quality of cancer-related care, and
      satisfaction with health care in the prior year. RESULTS: Eighty YAS (M age =
      27.7 years, M time since diagnosis = 10.4 years) participated. Just over half of
      YAS surveyed (n = 44, 55%) endorsed continuing cancer-related follow-up care
      since transfer. Those with cancer-related follow-up endorsed seeing subspecialty
      survivorship providers (n = 16, 44%) and primary care providers (n = 22, 50%) or
      utilizing a shared care model (n = 6, 14%). About a third of YAS endorsed seeing
      subspecialists (n = 29, 36%) or using other support services (n = 22, 27%). YAS
      perceived content of communication varied significantly depending on care model
      with less cancer-related content being discussed by primary care providers,
      though perceived quality of cancer-related care and satisfaction with health care
      was generally favorable. CONCLUSIONS: YAS report less than optimal engagement in
      cancer-related follow-up care and communication in their health care encounters.
      IMPLICATIONS FOR CANCER SURVIVORS: Young adult survivors should receive
      anticipatory guidance about expectations for delivery and content of adult
      focused cancer-related follow-up care.

PMID- 26303369
TI  - A prospective study of screen time in adolescence and depression symptoms in
      young adulthood.
AB  - OBJECTIVES: The purpose of this study was to examine the association between
      screen time in adolescence and depressive symptoms in young adulthood in a
      population-based cohort study of Danish adolescents. METHODS: Data were from a
      cohort of adolescents who were followed-up in young adulthood for a period of up
      to 12 years (1997-2010, mean 8.8 years, n=435). Information on television
      viewing, computer use, total screen time and other determinants of depression
      were obtained in adolescence. Depressive symptoms were obtained in young
      adulthood using the Major Depression Inventory (MDI) and classified as mild,
      moderate or severe depression. Mixed regression models were used to examine the
      associations, with adjustment for major confounders. RESULTS: In multivariable
      adjusted analyses, each additional hour/day spent watching television or screen
      viewing in adolescence was associated with 1.36 (95% CI 0.73-1.98) and 1.05 (95%
      CI 0.50-1.60), respectively, greater MDI depression summary score in young
      adulthood (p<0.001). In logistic regression models, each additional hour/day
      spent watching television or screen viewing was associated with 1.64 (95% CI 1.18
      2.27) and 1.58 (95% CI 1.18-2.12), respectively, greater odds of prevalent
      depression in young adulthood, and dose-response relationships were indicated.
      Additional adjustment for either cardiorespiratory fitness or BMI did not
      materially change the results. No significant associations were observed between
      adolescent computer use and depressive symptoms in young adulthood. CONCLUSIONS:
      Limiting screen time, particularly television viewing, during adolescence may be
      important for preventing depression in young adulthood.

PMID- 26303370
TI  - Supplemental nutrition assistance program participation and sugar-sweetened
      beverage consumption, overall and by source.
AB  - INTRODUCTION: This paper examined patterns in adults' sugar-sweetened beverage
      (SSB) consumption and caloric intake by Supplemental Nutrition Assistance Program
      (SNAP) participation status and by source of purchases in the United States (US).
      METHOD: Cross-sectional analysis of consumption of SSBs by source of purchases
      using 24-hour dietary recall data obtained from the US National Health and
      Nutrition Examination Survey 2003-2010 (N=17,891). Bivariate analysis and
      multivariable regressions were used to examine the association between SNAP
      participation and SSB calories consumed overall and by source. RESULTS: SSBs
      account for approximately 12% of total daily caloric intake (258 kcal) among SNAP
      participants, higher than that of SNAP-eligible nonparticipants (9% total daily
      intake, 205 kcal) and SNAP-ineligible nonparticipants (6% total daily intake, 153
      kcal). Among income-eligible adults, participating in SNAP is associated with
      28.9 additional SSB calories, of which most were obtained from a store. From 2003
      04 to 2009-10, SSB prevalence and caloric intake were flat among SNAP
      participants while it declined among both SNAP-eligible and SNAP-ineligible
      nonparticipants; this pattern held for all sources of SSBs except for those
      purchased from fast-food restaurants, which were not statistically reduced among
      nonparticipants. CONCLUSION: SNAP participants consumed more SSB calories
      compared to SNAP-eligible nonparticipants; and their SSB prevalence and caloric
      intake trend was flat over the 2003-04 to 2009-10 period. SNAP-Education
      interventions that focus on improving access to healthy food in poor
      neighborhoods may benefit SNAP participants.

PMID- 26303371
TI  - Assessing the usefulness of systematic reviews for policymakers in public health:
      A case study of overweight and obesity prevention interventions.
AB  - OBJECTIVE: Systematic reviews (SRs) should include policy-relevant information in
      order to more readily inform policy and practice. We investigated whether SRs of
      overweight and obesity prevention interventions are framed in such a way that
      maximises their usefulness for policymakers. METHOD: We conducted a systematic
      review of SRs of overweight and obesity prevention interventions published in 4
      databases any time up to December 2014. We analysed the SRs for their usefulness
      to policymakers, using a coding frame developed based on literature around what
      policymakers want and need from systematic reviews. Systematic reviews were
      assessed for a) policy links and framing; b) quality assessment and conflict of
      interest statements: and c) discussion of policy implications. RESULTS: Of the
      153 SRs that met the inclusion criteria, very few (7%) had authors from policy
      based organisations, 48% had funding from such organisations, and almost a third
      (31%) framed their introduction or aims around policy. Most (69%) discussed
      issues affecting generalisability of the SR findings but only a quarter (24%)
      discussed cost or cost-effectiveness of the intervention under investigation.
      Less than a third (29%) of SRs discussed the policy implications of their
      findings. SRs that were policy-framed were significantly more likely to discuss
      costs (PR=1.8, 95%CI 1.0-3.0) and policy implications (PR=2.5, 95%CI 1.5-4.0).
      CONCLUSION: SRs should discuss the policy and practice implications of their
      findings to maximise the influence of SRs on policy making. It is recommended
      that SR guidelines are updated to include generalisability and discussion of
      policy and practice implications as a requirement.

PMID- 26303372
TI  - Exercise facilitates smoking cessation indirectly via improvements in smoking
      specific self-efficacy: Prospective cohort study among a national sample of young
      smokers.
AB  - OBJECTIVE: The purpose of this study was to examine whether exercise is
      associated with 2-year follow-up smoking status through its influence on smoking
      specific self-efficacy. METHODS: Longitudinal data from the 2003-2005 National
      Youth Smoking Cessation Survey were used, including 1,228 participants (16-24
      years). A questionnaire was used to examine baseline exercise levels, baseline
      smoking-specific self-efficacy, follow-up smoking status, and the covariates.
      RESULTS: Baseline exercise was associated with baseline self-efficacy (beta=0.04,
      p<0.001) after adjusting for age category, sex, race-ethnicity, education, and
      nicotine dependence. Baseline self-efficacy, in turn, was associated with 2-year
      smoking status (beta=0.23, p<0.001) after adjustments. There was no adjusted
      direct effect of baseline exercise on 2-year smoking status (beta=0.001, p=0.95);
      however, the adjusted indirect effect of baseline self-efficacy on the
      relationship between exercise and 2-year smoking status was significant
      (beta=0.008, bootstrapped lower and upper CI: 0.002-0.02; p<0.05). The mediation
      ratio was 0.837, which indicates that smoking-specific self-efficacy mediates 84%
      of the total effect of exercise on smoking status. CONCLUSIONS: Among daily
      smokers, exercise may help to facilitate smoking cessation via exercise-induced
      increases in smoking-specific self-efficacy.

PMID- 26303373
TI  - Accounting for the daily locations visited in the study of the built environment
      correlates of recreational walking (the RECORD Cohort Study).
AB  - BACKGROUND: Understanding how built environment characteristics influence
      recreational walking is of the utmost importance to develop population-level
      strategies to increase levels of physical activity in a sustainable manner.
      PURPOSE: This study analyzes the residential and non-residential environmental
      correlates of recreational walking, using precisely geocoded activity space data.
      METHODS: The point-based locations regularly visited by 4365 participants of the
      RECORD Cohort Study (Residential Environment and CORonary heart Disease) were
      collected between 2011 and 2013 in the Paris region using the VERITAS software
      (Visualization and Evaluation of Regular Individual Travel destinations and
      Activity Spaces). Zero-inflated negative binomial regressions were used to
      investigate associations between both residential and non-residential
      environmental exposure and overall self-reported recreational walking over 7
      days. RESULTS: Density of destinations, presence of a lake or waterway, and
      neighborhood education were associated with an increase in the odds of reporting
      any recreational walking time. Only the density of destinations was associated
      with an increase in time spent walking for recreational purpose. Considering the
      recreational locations visited (i.e., sports and cultural destinations) in
      addition to the residential neighborhood in the calculation of exposure improved
      the model fit and increased the environment-walking associations, compared to a
      model accounting only for the residential space (Akaike Information Criterion
      equal to 52797 compared to 52815). CONCLUSIONS: Creating an environment
      supportive to walking around recreational locations may particularly stimulate
      recreational walking among people willing to use these facilities.

PMID- 26303374
TI  - Trends in the geographic distribution of nursing staff before and after the Great
      East Japan Earthquake: a longitudinal study.
AB  - BACKGROUND: Medical care systems in Iwate, Miyagi and Fukushima prefectures were
      greatly damaged by the Great East Japan Earthquake (GEJE), which struck on 11
      March 2011. The shortage of nurses in this area was concerning; however, temporal
      trends have not been investigated. This study aimed to investigate the trends in
      the geographic distribution of total nursing staff per population in the
      secondary medical areas (SMAs) of these prefectures before and after the GEJE. We
      also aimed to qualify the above trends. METHODS: We conducted a longitudinal
      study at four time points (July 2007, 2010, 2011 and 2013) over 6 years using
      reports of basic hospitalization charges from all hospitals within Iwate, Miyagi
      and Fukushima prefectures that experienced severe damage from the GEJE. We
      calculated the number of total nursing staff per population in the SMAs and
      compiled descriptive statistics. Changes from 2010 to 2013 were qualified and
      mapped. RESULTS: In coastal SMAs, the ratios of total nursing staff per
      population decreased immediately after the GEJE. In most SMAs in 2013, the ratios
      increased and exceeded the pre-GEJE level. However, the changes in total nursing
      staff per population from 2010 to 2013 were negative in Ryouban (-4.0%),
      Ishinomaki-Tome-Kesennuma (-1.9%), Sousou (-47.7%) and Iwaki (-1.9%). In Sousou,
      which is closest to the Fukushima Daiichi Nuclear Power Plant, the changes in
      total nursing staff per population qualified by job role were -33.7% for nurses, 
      57.7% for associate nurses and -63.2% for nursing aides. CONCLUSIONS: Our study
      indicated that the temporal trends in the number of total nursing staff per
      population due to the GEJE differed between the physically damaged areas and
      those affected by radiation. We also found the difference in the trend by
      qualifications: the reduction in total nursing staff per population was larger in
      Sousou, the area most affected by radiation, than in any other SMAs. Moreover,
      the number of nursing aides was most affected among the three types of staff. To
      promote the post-GEJE reconstruction of medical care systems, it might be
      necessary to develop policies to secure both nurses and nursing aides after
      nuclear disasters.

PMID- 26303375
TI  - Triggering of Suicidal Erythrocyte Death Following Boswellic Acid Exposure.
AB  - BACKGROUND/AIMS: The antinflammatory natural product boswellic acid is effective
      against cancer at least in part by inducing tumor cell apoptosis. Similar to
      apoptosis of nucleated cells erythrocytes may enter eryptosis, a suicidal death
      characterized by cell shrinkage and cell membrane scrambling with
      phosphatidylserine translocation to the erythrocyte surface. Stimulators of
      eryptosis include oxidative stress, increase of cytosolic Ca(2+)-activity
      ([Ca(2+)]i), energy depletion, ceramide formation and p38 kinase activation. The
      present study tested, whether and how boswellic acid induces eryptosis. METHODS:
      Phosphatidylserine exposure at the cell surface was estimated from annexin V
      binding, cell volume from forward scatter, hemolysis from hemoglobin release,
      [Ca(2+)]i from Fluo3-fluorescence, ceramide abundance utilizing specific
      antibodies, reactive oxygen species (ROS) from 2',7'-dichlorodihydrofuorescein
      diacetate (DCFDA) fluorescence, and cytosolic ATP concentration utilizing a
      luciferin-luciferase assay kit. RESULTS: A 24 hours exposure of human
      erythrocytes to boswellic acid (5 ug/ml) significantly increased the percentage
      of annexin-V-binding cells (to 9.3 +/- 0.9 %) and significantly decreased forward
      scatter. Boswellic acid did not significantly modify [Ca(2+)]i, cytosolic ATP,
      ROS, or ceramide abundance. The effect of boswellic acid on annexin-V-binding was
      significantly blunted, but not abolished by p38 kinase inhibitors skepinone (2
      uM) and SB203580 (2 uM). CONCLUSIONS: Boswellic acid stimulates cell shrinkage
      and phospholipid scrambling of the erythrocyte cell membrane, an effect in part
      dependent on p38 protein kinase activity.

PMID- 26303376
TI  - Editorial Comment to Reassessment of the risk factors for biochemical recurrence
      in D'Amico intermediate-risk prostate cancer treated using radical prostatectomy.

PMID- 26303377
TI  - Demonstration of elevated levels of active cathepsin S in dextran sulfate sodium
      colitis using a new activatable probe.
AB  - BACKGROUND: Proteases play a major role in inflammatory diseases of the
      gastrointestinal tract. Activatable probes are a major technological advance,
      enabling sensitive detection of active proteases in tissue samples. Our aim was
      to synthesize an activatable probe for cathepsin S and validate its use in a
      mouse model of colitis. METHODS: We designed and synthesized a new fluorescent
      activatable probe, NB200, for the detection of active cathepsin S. Colitis was
      induced in C57BL/6 mice by the administration of 3% dextran sulfate sodium (DSS).
      Homogenized mouse colons, with or without the addition of the specific cathepsin
      S inhibitor MV026031, were incubated with NB200 in a fluorescent plate reader.
      KEY RESULTS: NB200 selectively detected purified cathepsin S and not other common
      inflammatory proteases. Homogenates of colon from mice with DSS colitis induced a
      significant fluorescent increase when compared to control animals (control vs
      DSS: p < 0.05 at 200 min and p < 0.01 at 220-240 min), indicating cathepsin S
      activation. The cathepsin S inhibitor abolished this increase in fluorescence
      (DSS vs DSS + MV026031: p < 0.05 at 140 min, p < 0.01 at 180 min, p < 0.001 at
      200-240 min), which confirms cathepsin S activation. Cathepsin S activity
      correlated with the disease activity index (Spearman r = 0.77, p = 0.017).
      CONCLUSIONS & INFERENCES: Our investigation has demonstrated the utility of
      activatable probes for detecting protease activity in intestinal inflammation.
      Panels of such probes may allow 'signature' protease profiles to be established
      for a range of inflammatory diseases and disorders.

PMID- 26303379
TI  - Endocrine stress responses and risk of type 2 diabetes mellitus.
AB  - This study was carried to ascertain whether stress responses are associated with
      abnormalities in glucose tolerance, insulin sensitivity and pancreatic beta cell
      function and risk of type 2 Diabetes Mellitus. Salivary cortisol, a marker of
      hypothalamic-pituitary-adrenal (HPA) axis and salivary alpha-amylase, a marker of
      sympathetic nervous system (SNS) were compared in 125 subjects of newly detected
      diabetes mellitus (NDDM) and normal glucose tolerance (NGT) subjects who were
      diagnosed on the basis of oral glucose tolerance test (OGTT). Assessment of
      stress in them was done through stress scales - presumptive stressful life events
      scale (PSLES), perceived stress scale (PSS) and sense of coherence (SOC) and
      correlated with these and other stress response markers. Significantly higher 10
      pm salivary cortisol and post dexamethasone salivary cortisol were found in NDDM
      subjects as compared to NGT. 10 pm salivary cortisol correlated significantly
      with fasting plasma glucose (FPG), 2 h plasma glucose (2h PG) and glycated
      hemoglobin (HbA1c) while post dex salivary cortisol correlated with 2h PG, HbA1c
      and salivary alpha-amylase with 2h PG. Stepwise logistic regression analysis
      showed that body mass index (OR: 1.840), SOC (OR: 0.688) and 10 pm salivary
      cortisol (OR: 1.427) were the strongest predictors of NDDM. The results of the
      present study indicate that NDDM subjects display significantly higher chronic
      stress and stress responses when compared to subjects with NGT. Chronic stress
      and endocrine stress responses are significantly associated with glucose
      intolerance, insulin resistance and diabetes mellitus. 

PMID- 26303380
TI  - Effects of cerulein on keratin 8 phosphorylation and perinuclear reorganization
      in pancreatic cancer cells: Involvement of downregulation of protein phosphatase
      2A and alpha4.
AB  - Toxicants can perturb cellular homeostasis by modifying phosphorylation-based
      signaling. In the present study, we examined the effects of cerulein, an inducer
      of acute pancreatitis, on keratin 8 (K8) phosphorylation. We found that cerulein
      dose-dependently induced K8 phosphorylation and perinuclear reorganization in
      PANC-1 cells, thus leading to migration and invasion. The extracellular signal
      regulated kinases (ERK) inhibitor U0126 suppressed cerulein-induced
      phosphorylation of serine 431 and reorganization of K8. Cerulein reduced the
      expressions of protein phosphatase 2A (PP2A) via ubiqutination and alpha4. PP2A's
      involvement in K8 phosphorylation of PANC-1 cells was also confirmed by the
      observation that PP2A gene silencing resulted in K8 phosphorylation and migration
      of PANC-1 cells. Overall, these results suggest that cerulein induced
      phosphorylation and reorganization through ERK activation by downregulating PP2A
      and alpha4, leading to increased migration and invasion of PANC-1 cells. (c) 2015
      Wiley Periodicals, Inc. Environ Toxicol 31: 2090-2098, 2016.

PMID- 26303381
TI  - Microsatellite marker development based on next-generation sequencing for the
      smooth marron (Cherax cainii, Austin) and cross-species amplification in other
      Cherax species.
AB  - BACKGROUND: The smooth marron, Cherax cainii is an important freshwater
      crustacean species for aquaculture and for a local wild fishery. C. tenuimanus,
      commonly known as the hairy marron is under threat from environmental impacts and
      genetic introgression from C. cainii that is hampering the survival of wild C.
      tenuimanus stocks. Marron are endemic to the south-west of Western Australia and
      C. tenuimanus is restricted to only the Margaret River. RESULTS: To isolate
      microsatellite sequences, shotgun 454 pyrosequencing was performed resulting in
      184,981 DNA sequence reads. Following screening for microsatellites, 8799
      putative microsatellite loci were detected and PCR primers were designed for 968
      of these. Ten microsatellite loci were screened in 30 captive C. cainii
      individuals with eight loci producing unambiguous results. The average number of
      alleles per locus was 4.7 and average H e was 0.474. Following an analysis of
      relatedness, 79% of captive dyads were assigned as unrelated. Utilising C.
      quadricarinatus and C. destructor, cross-species amplification tests were
      conducted and amplification was achieved at four of the eight loci. CONCLUSIONS:
      Using next-generation sequencing methods, eight polymorphic microsatellite loci
      were developed from C. cainii, with potential for cross amplification in other
      Cherax species. The markers can be utilised for studies of natural genetic stock
      structure and for monitoring relatedness levels and genetic variation in both
      wild and captive populations.

PMID- 26303383
TI  - Hobnail-variant of papillary thyroid carcinoma in liquid-based cytology.

PMID- 26303382
TI  - Screening of potential targets in Plasmodium falciparum using stage-specific
      metabolic network analysis.
AB  - The Apicomplexa parasite Plasmodium is a major cause of death in developing
      countries which are less equipped to bring new medicines to the market. Currently
      available drugs used for treatment of malaria are limited either by inadequate
      efficacy, toxicity and/or increased resistance. Availability of the genome
      sequence, microarray data and metabolic profile of Plasmodium parasite offers an
      opportunity for the identification of stage-specific genes important to the
      organism's lifecycle. In this study, microarray data were analysed for
      differential expression and overlapped onto metabolic pathways to identify
      differentially regulated pathways essential for transition to successive
      erythrocytic stages. The results obtained indicate that S-adenosylmethionine
      decarboxylase/ornithine decarboxylase, a bifunctional enzyme required for
      polyamine synthesis, is important for the Plasmodium cell growth in the absence
      of exogenous polyamines. S-adenosylmethionine decarboxylase/ornithine
      decarboxylase is a valuable target for designing therapeutically useful
      inhibitors. One such inhibitor, [Formula: see text]-difluoromethyl ornithine, is
      currently in use for the treatment of African sleeping sickness caused by
      Trypanosoma brucei. Structural studies of ornithine decarboxylase along with
      known inhibitors and their analogues were carried out to screen drug databases
      for more effective and less toxic compounds. 

PMID- 26303384
TI  - In situ synthesis and hydrothermal crystallization of nanoanatase TiO2 -SiO2
      coating on aramid fabric (HTiSiAF) for UV protection.
AB  - TiO2 -SiO2 thin film was prepared by sol-gel method and coated on the aramid
      fabric to prepare functional textiles. The aramid fabric was dipped and withdrawn
      in TiO2 -SiO2 gel and hydrothermal crystallization at 80( degrees ) C, then its
      UV protection functionality was evaluated. The crystalline phase and the surface
      morphology of TiO2 -SiO2 thin film were characterized using SEM, XRD, and AFM
      respectively. SEM showed hydrothermal crystallization led to a homogeneous
      dispersion of anatase nonocrystal in TiO2 -SiO2 film, and XRD suggested the mean
      particle size of the formed anatase TiO2 was less than 30 nm. AFM indicated that
      hydrothermal treatment enhanced the crystallization of TiO2 . UV protection
      analysis suggested that the hydrothermally treated coated textile had a better
      screening property in comparison with TiO2 -SiO2 gel and native aramid fabric.

PMID- 26303385
TI  - PR Prolongation and Cardiac 123I-MIBG Uptake Reduction in Parkinson's Disease.
AB  - BACKGROUND: Cardiac 123I-metaiodobenzylguanidine scintigraphy (MIBG) previously
      demonstrated an uptake reduction in patients with Parkinson's disease (PD).
      However, epidemiologic research showed that electrocardiography (ECG)
      abnormalities occurred prior to motor signs in PD. Here we investigated whether
      the electrical conduction system of the heart was impaired in PD. METHODS:
      Clinical features, ECG and MIBG parameters were analyzed in 191 patients with PD,
      42 with multiple system atrophy (MSA) and 124 normal controls (NL). RESULTS: The
      PR interval was significantly longer in patients with PD than in NL. The PR
      interval was significantly negatively correlated with early and delayed heart-to
      mediastinum ratios in MIBG scintigraphy in PD and MSA patients. In 19 PD patients
      with PR prolongation, 17 patients also had abnormal MIBG findings, and the other
      2 showed normal MIBG. CONCLUSIONS: The PR prolongation must show some sympathetic
      system abnormality because it is mainly controlled by the sympathetic nervous
      system. PR prolongation supports the objective biomarker value of MIBG for PD
      diagnosis.

PMID- 26303386
TI  - Peptide-assembled graphene oxide as a fluorescent turn-on sensor for
      lipopolysaccharide (endotoxin) detection.
AB  - Lipopolysaccharide (LPS) is a toxic inflammatory stimulator released from the
      outer cell membrane of Gram-negative bacteria, known to be directly related to,
      for example, septic shock, that causes millions of casualties annually. This
      number could potentially be lowered significantly if specific, sensitive, and
      more simply applicable LPS biosensors existed. In this work, we present a facile,
      sensitive and selective LPS sensor, developed by assembling tetramethylrhodamine
      labeled LPS-binding peptides on graphene oxide (GO). The fluorescence of the dye
      labeled peptide is quenched upon interaction with GO. Specific binding to LPS
      triggers the release of the peptide-LPS complex from GO, resulting in
      fluorescence recovery. This fluorescent turn-on sensor offers an estimated limit
      of detection of 130 pM, which is the lowest ever reported among all synthetic LPS
      sensors to date. Importantly, this sensor is applicable for detection of LPS in
      commonly used clinical injectable fluids, and it enables selective detection of
      LPS from different bacterial strains as well as LPS on the membrane of living E.
      coli. 

PMID- 26303387
TI  - Genetic and epigenetic characterization of low-grade gliomas reveals frequent
      methylation of the MLH3 gene.
AB  - Diffuse astrocytomas and oligodendrogliomas (WHO grade II) are the most common
      histological subtypes of low-grade gliomas (LGGs). Several molecular and
      epigenetic markers have been identified that predict tumor progression. Our aim
      was in detail to investigate the genetic and epigenetic background of LGGs and to
      identify new markers that might play a role in tumor behavior. Twenty-three
      patients with oligodendroglioma or oligoastrocytoma (LGO) and 22 patients with
      diffuse astrocytoma (LGA) were investigated using several molecular-cytogenetic
      and molecular methods to assess their copy number variations, mutational status
      and level of promoter methylation. The most frequent findings were a 1p/19q
      codeletion in 83% of LGO and copy-neutral loss of heterozygosity (CN-LOH) of 17p
      in 72% of LGA. Somatic mutations in the isocitrate dehydrogenase 1 or 2
      (IDH1/IDH2) genes were detected in 96% of LGO and 91% of LGA. The O-6
      methylguanine-DNA-methyltransferase (MGMT) promoter was methylated in 83% of LGO
      and 59% of LGA. MutL homolog 3 (MLH3) promoter methylation was observed in 61% of
      LGO and 27% of LGA. Methylation of the MGMT promoter, 1p/19q codeletion, mutated
      IDH1, and CN-LOH of 17p were the most frequent genetic aberrations in LGGs. The
      findings were more diverse in LGA than in LGO. To the best of our knowledge, this
      is the first time description of methylation of the MLH3 gene promoter in LGGs.
      Further studies are required to determine the role of the methylated MLH3
      promoter and the other aberrations detected.

PMID- 26303388
TI  - Correlated random walks caused by dynamical wavefunction collapse.
AB  - Wavefunction collapse models modify Schrodinger's equation so that it describes
      the collapse of a superposition of macroscopically distinguishable states as a
      dynamical process. This provides a basis for the resolution of the quantum
      measurement problem. An additional generic consequence of the collapse mechanism
      is that it causes particles to exhibit a tiny random diffusive motion. Here it is
      shown that for the continuous spontaneous localization (CSL) model-one of the
      most well developed collapse models-the diffusions of two sufficiently nearby
      particles are positively correlated. An experimental test of this effect is
      proposed in which random displacements of pairs of free nanoparticles are
      measured after they have been simultaneously released from nearby traps. The
      experiment must be carried out at sufficiently low temperature and pressure in
      order for the collapse effects to dominate over the ambient environmental noise.
      It is argued that these constraints can be satisfied by current technologies for
      a large region of the viable parameter space of the CSL model. The effect
      disappears as the separation between particles exceeds the CSL length scale. The
      test therefore provides a means of bounding this length scale.

PMID- 26303389
TI  - Theoretical study of a simple rotational-echo double-resonance NMR for
      homonuclear spin-1/2 pairs.
AB  - We investigate theoretically intriguing aspects of a simple rotational-echo
      double-resonance (REDOR) NMR technique for homonuclear spin-1/2 pairs undergoing
      MAS. The simple technique sets Gaussian soft pi pulses at every half MAS
      rotational period in the pulse sequence. The reduction in rotational echo
      amplitude (the REDOR echo reduction) is observed at the end of the evolution
      period te  = (n + 1)Tr, where Tr is a MAS rotational period. The exact average
      Hamiltonians for the homonuclear REDOR (hm-REDOR) technique are calculated by
      dividing the evolution period into four periods. We show theoretically and
      experimentally that the hm-REDOR technique produces the REDOR echo reductions for
      homonuclear spin-1/2 pairs. In addition, the theoretical results reveal that the
      REDOR echo reductions are independent of the chemical-shift difference, delta,
      under a simple condition of kappa = delta/omegar  >= 6 and te  < 10 ? (1/d'),
      where omegar is the sample spinning frequency and d' is the dipolar coupling
      constant expressed in Hz. We call this simple condition the master condition.
      This means that the REDOR echo reductions for a homonuclear spin-1/2 pair can be
      calculated under the master condition by considering only d' and omegar , which
      is the case for a heteronuclear spin pair. Finally, we demonstrate that four
      phase cycling yields the multiple-quantum filtered hm-REDOR experiment, where the
      appearance of the REDOR echo reductions shows that the echo reductions are
      definitely attributable to the homonuclear dipolar interaction even if there is a
      slight unwanted effect from the recovered chemical-shift anisotropy in these
      reductions.

PMID- 26303390
TI  - Depression and anxiety before and after limb length discrepancy correction in
      patients with unilateral developmental dysplasia of the hip.
AB  - OBJECTIVE: Limb length discrepancy (LLD) is common in patients with developmental
      dysplasia of the hip (DDH) and may influence the psychological status of these
      patients. The present study aims to investigate depression and anxiety in DDH
      patients with different extents of LLD and to assess the effect of LLD correction
      on these two psychological factors. METHODS: 161 patients with DDH were recruited
      and divided into two groups based on whether they could perceive LLD
      preoperatively. The patients who could not perceive LLD were assigned to group N,
      and those who could perceive LLD were assigned to group P. Depression/anxiety,
      Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and
      LLD were assessed one week before, six months and two years after total hip
      arthroplasty (THA). RESULTS: Depression and anxiety were significantly higher in
      group P patients compared to group N patients. The patients in group N presented
      significant improvement in depression and anxiety six months after arthroplasty,
      while DDH patients in group P did two years after arthroplasty. Correlation
      analyses revealed their improvement was associated with pain relief and improved
      hip function in both groups of patients and was also related to changes in the
      perception of LLD in group P patients. CONCLUSIONS: Depression and anxiety levels
      were higher in DDH patients with perceived LLD. Their improvement was related to
      pain relief and improved hip function following THA. In DDH patients with
      perceived LLD, a change in the perception of LLD also played a part in their
      improvement.

PMID- 26303391
TI  - Phobalysin, a Small beta-Pore-Forming Toxin of Photobacterium damselae subsp.
      damselae.
AB  - Photobacterium damselae subsp. damselae, an important pathogen of marine animals,
      may also cause septicemia or hyperaggressive necrotizing fasciitis in humans. We
      previously showed that hemolysin genes are critical for virulence of this
      organism in mice and fish. In the present study, we characterized the hlyA gene
      product, a putative small beta-pore-forming toxin, and termed it phobalysin P
      (PhlyP), for "photobacterial lysin encoded on a plasmid." PhlyP formed stable
      oligomers and small membrane pores, causing efflux of K(+), with no significant
      leakage of lactate dehydrogenase but entry of vital dyes. The latter feature
      distinguished PhlyP from the related Vibrio cholerae cytolysin. Attack by PhlyP
      provoked a loss of cellular ATP, attenuated translation, and caused profound
      morphological changes in epithelial cells. In coculture experiments with
      epithelial cells, Photobacterium damselae subsp. damselae led to rapid hemolysin
      dependent membrane permeabilization. Unexpectedly, hemolysins also promoted the
      association of P. damselae subsp. damselae with epithelial cells. The collective
      observations of this study suggest that membrane-damaging toxins commonly enhance
      bacterial adherence. 

PMID- 26303394
TI  - Synthesis and electronic properties of pi-extended flavins.
AB  - Flavin derivatives with an extended pi-conjugation were synthesized in moderate
      to good yields from aryl bromides via a Buchwald-Hartwig palladium catalyzed
      amination protocol, followed by condensation of the corresponding aromatic amines
      with violuric acid. The electronic properties of the new compounds were
      investigated by absorption and emission spectroscopy, cyclic voltammetry, density
      functional theory (DFT) and time dependent density functional theory (TDDFT). The
      compounds absorb up to 550 nm and show strong luminescence. The photoluminescence
      quantum yields phiPL measured in dichloromethane reach 80% and in PMMA
      (poly(methyl methacrylate)) 77%, respectively, at ambient temperature. The
      electrochemical redox behaviour of pi-extended flavins follows the mechanism
      previously described for the parent flavin. 

PMID- 26303392
TI  - A Duplicated ESAT-6 Region of ESX-5 Is Involved in Protein Export and Virulence
      of Mycobacteria.
AB  - The ESX-5 secretion system of Mycobacterium tuberculosis is important for
      bacterial virulence and for the secretion of the large PE/PPE protein family,
      whose genes constitute 10% of the M. tuberculosis genome. A four-gene region of
      the ESX-5 system is duplicated three times in the M. tuberculosis genome, but the
      functions of these duplicates are unknown. Here we investigated one of these
      duplicates: the region carrying the esxI, esxJ, ppe15, and pe8 genes (ESX-5a). An
      ESX-5a deletion mutant in the model system M. marinum background was deficient in
      the secretion of some members of the PE/PPE family of proteins. Surprisingly, we
      also identified other proteins that are not members of this family, thus
      expanding the range of ESX-5 secretion substrates. In addition, we demonstrated
      that ESX-5a is important for the virulence of M. marinum in the zebrafish model.
      Furthermore, we showed the role of the M. tuberculosis ESX-5a region in
      inflammasome activation but not host cell death induction, which is different
      from the case for the M. tuberculosis ESX-5 system. In conclusion, the ESX-5a
      region is nonredundant with its ESX-5 paralog and is necessary for secretion of a
      specific subset of proteins in M. tuberculosis and M. marinum that are important
      for bacterial virulence of M. marinum. Our findings point to a role for the three
      ESX-5 duplicate regions in the selection of substrates for secretion via ESX-5,
      and hence, they provide the basis for a refined model of the molecular mechanism
      of this type VII secretion system. 

PMID- 26303393
TI  - Erythrocytic Iron Deficiency Enhances Susceptibility to Plasmodium chabaudi
      Infection in Mice Carrying a Missense Mutation in Transferrin Receptor 1.
AB  - The treatment of iron deficiency in areas of high malaria transmission is
      complicated by evidence which suggests that iron deficiency anemia protects
      against malaria, while iron supplementation increases malaria risk. Iron
      deficiency anemia results in an array of pathologies, including reduced systemic
      iron bioavailability and abnormal erythrocyte physiology; however, the mechanisms
      by which these pathologies influence malaria infection are not well defined. In
      the present study, the response to malaria infection was examined in a mutant
      mouse line, Tfrc(MRI24910), identified during an N-ethyl-N-nitrosourea (ENU)
      screen. This line carries a missense mutation in the gene for transferrin
      receptor 1 (TFR1). Heterozygous mice exhibited reduced erythrocyte volume and
      density, a phenotype consistent with dietary iron deficiency anemia. However,
      unlike the case in dietary deficiency, the erythrocyte half-life, mean
      corpuscular hemoglobin concentration, and intraerythrocytic ferritin content were
      unchanged. Systemic iron bioavailability was also unchanged, indicating that this
      mutation results in erythrocytic iron deficiency without significantly altering
      overall iron homeostasis. When infected with the rodent malaria parasite
      Plasmodium chabaudi adami, mice displayed increased parasitemia and succumbed to
      infection more quickly than their wild-type littermates. Transfusion of
      fluorescently labeled erythrocytes into malaria parasite-infected mice
      demonstrated an erythrocyte-autonomous enhanced survival of parasites within
      mutant erythrocytes. Together, these results indicate that TFR1 deficiency alters
      erythrocyte physiology in a way that is similar to dietary iron deficiency
      anemia, albeit to a lesser degree, and that this promotes intraerythrocytic
      parasite survival and an increased susceptibility to malaria in mice. These
      findings may have implications for the management of iron deficiency in the
      context of malaria. 

PMID- 26303395
TI  - Hymenobacter mucosus sp. nov., isolated from a karst cave soil sample.
AB  - A novel Gram-stain-negative, non-motile, rod-shaped and watermelon-red-pigmented
      aerobic bacterial strain, designated YIM 77969T, was isolated from a soil sample
      of Jiuxiang cave, a tourism cave located in Yiliang county, Yunnan province,
      south-west China. Phylogenetic analysis based on the 16S rRNA gene sequence
      indicated that strain YIM 77969T belongs to the genus Hymenobacter, and was
      closely related to Hymenobacter tibetensis XTM003T (96.58 %), Hymenobacter
      gelipurpurascens Txg1T (96.02 %) and Hymenobacter xinjiangensis X2-1gT (95.80 %).
      Growth of strain YIM 77969T occurred at 5-35  degrees C, at pH 5.0-9.0 and in the
      presence of 0-1 % (w/v) NaCl. The predominant menaquinone was MK-7. The major
      fatty acids were iso-C15 : 0, C16 : 1omega5c and summed feature 3 (C16 : 1omega7c
      and/or C16 : 1omega6c). The polar lipid profiles consisted of the major compound
      phosphatidylethanolamine, two unknown aminolipids, three unknown
      aminophospholipids, one glycolipid and one unknown polar lipid. Pigment analysis
      showed that the pigment belonged to the plectaniaxanthin series of carotenoid
      pigments. The genomic DNA G+C content was 55.2 mol%. On the basis of
      phylogenetic, phenotypic and chemotaxonomic characteristics, strain YIM 77969T is
      considered to represent a novel species of the genus Hymenobacter, for which the
      name Hymenobacter mucosus sp. nov. is proposed. The type strain is YIM 77969T ( =
      KCTC 32567T = DSM 28041T).

PMID- 26303397
TI  - Efficacy of physical therapy for the treatment of lateral epicondylitis: a meta
      analysis.
AB  - BACKGROUND: Physical therapy for the treatment of lateral epicondylitis (LE)
      often comprises movement therapies, extracorporeal shockwave therapy (ECSWT), low
      level laser therapy (LLLT), low frequency electrical stimulation or pulsed
      electromagnetic fields. Still, only ECSWT and LLLT have been meta-analytically
      researched. METHODS: PUBMED, EMBASE and Cochrane database were systematically
      searched for randomized controlled trials (RCTs). Methodological quality of each
      study was rated with an adapted version of the Scottish Intercollegiate
      Guidelines Network (SIGN) checklist. Pain reduction (the difference between
      treatment and control groups at the end of trials) and pain relief (the change in
      pain from baseline to the end of trials) were calculated with mean differences
      (MD) and 95%-Confidence intervals (95 % CI). RESULTS: One thousand one hundred
      thirty eight studies were identified. One thousand seventy of those did not meet
      inclusion criteria. After full articles were retrieved 16 studies met inclusion
      criteria and 12 studies reported comparable outcome variables. Analyses were
      conducted for overall pain relief, pain relief during maximum handgrip strength
      tests, and maximum handgrip strength. There were not enough studies to conduct an
      analysis of physical function or other outcome variables. CONCLUSIONS:
      Differences between treatment and control groups were larger than differences
      between treatments. Control group gains were 50 to 66% as high as treatment group
      gains. Still, only treatment groups with their combination of therapy specific
      and non-therapy specific factors reliably met criteria for clinical relevance.
      Results are discussed with respect to stability and their potential meaning for
      the use of non-therapy specific agents to optimize patients' gain.

PMID- 26303398
TI  - Exploration of contextual factors in a successful quality improvement
      collaborative in English ambulance services: cross-sectional survey.
AB  - RATIONALE, AIMS AND OBJECTIVES: Clinical leadership and organizational culture
      are important contextual factors for quality improvement (QI) but the
      relationship between these and with organizational change is complex and poorly
      understood. We aimed to explore the relationship between clinical leadership,
      culture of innovation and clinical engagement in QI within a national ambulance
      QI Collaborative (QIC). METHODS: We used a self-administered online questionnaire
      survey sent to front-line clinicians in all 12 English ambulance services. We
      conducted a cross-sectional analysis of quantitative data and qualitative
      analysis of free-text responses. RESULTS: There were 2743 (12% of 22 117)
      responses from 11 of the 12 participating ambulance services. In the 3% of
      responders that were directly involved with the QIC, leadership behaviour was
      significantly higher than for those not directly involved. QIC involvement made
      no significant difference to responders' perceptions of the culture of innovation
      in their organization, which was generally considered poor. Although uptake of QI
      methods was low overall, QIC members were significantly more likely to use QI
      methods, which were also significantly associated with leadership behaviour.
      CONCLUSIONS: Despite a limited organizational culture of innovation, clinical
      leadership and use of QI methods in ambulance services generally, the QIC
      achieved its aims to significantly improve pre-hospital care for acute myocardial
      infarction and stroke. We postulate that this was mediated through an improvement
      subculture, linked to the QIC, which facilitated large-scale improvement by
      stimulating leadership and QI methods. Further research is needed to understand
      success factors for QI in complex health care environments.

PMID- 26303399
TI  - Optimization is required when using linked hospital and laboratory data to
      investigate respiratory infections.
AB  - OBJECTIVE: Despite a recommendation for microbiological testing, only 45% of
      children hospitalized for respiratory infections in our previous data linkage
      study linked to a microbiological record. We conducted a chart review to validate
      linked microbiological data. STUDY DESIGN AND SETTING: The chart review consisted
      of children aged <5 years admitted to seven selected hospitals for respiratory
      infections in Western Australia, 2000-2011. We calculated the proportion of
      admissions where testing was performed and any pathogens detected. We compared
      these proportions between the chart review and our previous data linkage study.
      Poisson regression was used to identify factors predicting the likelihood of
      microbiological tests in the chart review cohort. RESULTS: From the chart review,
      77% of 746 records had a microbiological test performed compared with 46% of
      18,687 records from our previous data linkage study. Of those undergoing testing,
      66% of the chart review and 64% of data linkage records had >=1 respiratory
      pathogen(s) detected. In the chart review cohort, frequency of testing was
      highest in children admitted to metropolitan hospitals. CONCLUSION: Validation
      studies are essential to ensure the quality of linked data. Our previous data
      linkage study failed to capture all relevant microbiological records. Findings
      will be used to optimize extraction protocols for future linkage studies.

PMID- 26303400
TI  - Informing a realistic laboratory erosion-testing regime--observations.
AB  - OBJECTIVES: To measure aspects of fizzy drink consumption in a social environment
      to inform the development of a laboratory testing regime. METHODS: This was an
      observational study in which participants were invited to attend one of four
      pizza and soft drink parties. All such foods and drinks were served in an air
      conditioned room at a temperature of 24 degrees C. All drinks were at a
      temperature of 4 degrees C and each participant was asked to spit out, into
      graduated cups, their first and second sips. Both the temperature and volume of
      these were measured. Upon completion of the party the volume of drinks consumed
      was determined. Video footage of the experiment was recorded for subsequent
      analysis to determine sip count and the elapsed time period between first and
      last sip. These values were compared to the analogous measured value of
      expectorated volume in order to assess the usefulness of video observation in the
      context of this work. RESULTS: The mean expectorated beverage temperature was
      14.9+/-2.0 degrees C. The mean time spent drinking was 44.2+/-17.4 minutes with a
      mean consumption rate of 13.3+/-6.0 ml/min. Only the sip volume and sip count per
      can values were significantly different between sexes (P<0.05) with females
      displaying lower values for volume and a higher sip count. There was close
      agreement between the sip volume values observed and calculated using video
      observation derived parameters. CONCLUSIONS: Several human drinking behaviour
      values were reported in this study and these will be of value in the development
      of more realistic laboratory erosion-testing regimes. It is concluded, within the
      limitations of this work, that (1) there are differences in the drinking
      behaviour of males and females with respect to sip volume and count, (2) the
      intraoral rise in temperature of a 4 degrees C beverage is lower than that used
      in previous laboratory simulations and (3) the values derived from video
      observation agree with those measured directly validating this technique for use
      in further studies. CLINICAL SIGNIFICANCE: The work provides valuable
      quantitative data on which to base simulated laboratory erosion work. Perhaps the
      most significant finding is that sipped beverages attain a temperature of only
      14.9 degrees C.

PMID- 26303401
TI  - One-year follow-up of at-home bleaching in smokers before and after dental
      prophylaxis.
AB  - OBJECTIVE: This clinical study evaluated the color longevity after one-year of at
      home bleaching with 10% carbamide peroxide (CP) in smokers and nonsmokers.
      METHODS: Sixty patients, 30 smokers and 30 non-smokers were subjected to
      bleaching with 10% CP during three hours daily for three weeks. The color was
      measured at baseline and one week, one month and one year after the completion of
      dental bleaching using the spectrophotometer Vita Easyshade (DeltaE*), shade
      guide Vita classical organized by value and Vita Bleachedguide 3D-MASTER
      (DeltaSGU). In the one-year recall, the color was assessed before and after
      dental prophylaxis with Robinson brush and prophylaxis paste. Data from color
      evaluation were analyzed by two-way repeated measures ANOVA and Tukey's test for
      the contrast of means (alpha=0.05). RESULTS: Twenty-seven smokers and 28 non
      smokers attended the one-year recall. For both study groups, only the main factor
      assessment time was statistically significant for DeltaSGU (Vita classical) and
      DeltaE* (p<0.001). Effective whitening was observed for both groups at baseline,
      which was stable at one-month and one year after dental prophylaxis. A slight
      darkening was observed after one year when the color was measured without
      prophylaxis. For the Vita Bleachedguide 3D-MASTER, color rebound was observed
      irrespectively of dental prophylaxis. CONCLUSION: The bleaching with 10% CP
      remained stable in both groups as long as extrinsic stains from diet and
      cigarette smoke were removed by professional dental prophylaxis. CLINICAL TRIALS
      REGISTRY: NCT02017873. CLINICAL RELEVANCE: The results of this study indicate
      that the bleaching is effective in smokers even after one-year, but dental
      prophylaxis may be necessary to remove extrinsic stains caused by diet and
      smoking.

PMID- 26303396
TI  - STUDIES IN FETAL BEHAVIOR: REVISITED, RENEWED, AND REIMAGINED.
AB  - Among the earliest volumes of this monograph series was a report by Lester Sontag
      and colleagues, of the esteemed Fels Institute, on the heart rate of the human
      fetus as an expression of the developing nervous system. Here, some 75 years
      later, we commemorate this work and provide historical and contemporary context
      on knowledge regarding fetal development, as well as results from our own
      research. These are based on synchronized monitoring of maternal and fetal
      parameters assessed between 24 and 36 weeks gestation on 740 maternal-fetal pairs
      compiled from eight separate longitudinal studies, which commenced in the early
      1990s. Data include maternal heart rate, respiratory sinus arrhythmia, and
      electrodrmal activity and fetal heartrate, motor activity, and their integration.
      Hierarchical linear modeling of developmental trajectories reveals that the fetus
      develops in predictable ways consistent with advancing parasympathetic
      regulation. Findings also include:within-fetus stability (i.e., preservation of
      rank ordering over time) for heart rate, motor, and coupling measures; a
      transitional period of decelerating development near 30 weeks gestation; sex
      differences in fetal heart rate measures but not in most fetal motor activity
      measures; modest correspondence in fetal neurodevelopment among siblings as
      compared to unrelated fetuses; and deviations from normative fetal development in
      fetuses affected by intrauterine growth restriction and other conditions.
      Maternal parameters also change during this period of gestation and there is
      evidence that fetal sex and individual variation in fetal neurobehavior influence
      maternal physio-logical processes and the local intrauterine context. Results are
      discussed within the framework of neuromaturation, the emergence of individual
      differences, and the bidirectional nature of the maternal-fetal relationship.We
      pose a number of open questions for future research. Although the human fetus
      remains just out of reach, new technologies portend an era of accelerated
      discovery of the earliest period of development

PMID- 26303402
TI  - Predictors of Sexual Assault-Specific Prosocial Bystander Behavior and
      Intentions: A Prospective Analysis.
AB  - This study prospectively examined the impact of men's own attitudes and behaviors
      and perceptions of peer attitudes and behaviors on intentions and engagement in
      prosocial bystander behavior. Undergraduate men completed surveys at baseline and
      4- and 7-month follow-ups. Men's perceptions of peer attitudes and behaviors and
      their own attitudes and behaviors were both important predictors of intentions.
      However, men's own attitudes and behaviors appeared to be more robustly
      predictive of behavior. Intentions to engage in bystander behavior were not
      predictive of behavior. Results support two specific areas of bystander
      intervention programming addressing misperceptions of social norms and personal
      attitudes and behaviors. 

PMID- 26303403
TI  - PROMETHEUS: an observational, cross-sectional, retrospective study of
      hypertriglyceridemia in Russia.
AB  - BACKGROUND: Data regarding the prevalence of hypertriglyceridemia in the Russian
      population are lacking, despite triglyceride (TG)-mediated pathways being causal
      in cardiovascular disease. The prevalence of mixed dyslipidemia and severe
      hypertriglyceridemia in the Russian population (PROMETHEUS) was undertaken to
      address this gap. METHODS: This was an observational, cross-sectional
      retrospective study. Data from adults with a full/partial lipoprotein record who
      had blood analyses done at an INVITRO laboratory in Russia between January 1,
      2011 and December 31, 2013 were analyzed. The primary endpoint was the prevalence
      of hypertriglyceridemia (TG >= 1.7 mmol/L); secondary endpoints included
      prevalence of borderline high, high, and very high TG and severe
      hypertriglyceridemia, defined as a TG level of 1.7 to <2.3, 2.3 to <5.6, >=5.6,
      and >=10.0 mmol/L, respectively. Statistical analyses involved the Wilcoxon and
      the Chi square tests. Correlations between log-transformed TG and low- and high
      density lipoprotein cholesterol (LDL-C and HDL-C) and total cholesterol (TC) were
      assessed. The correlation between glycated hemoglobin (HbA1c) and TG levels in a
      nested sample of subjects with HbA1c and TG data was also assessed using a log
      linear model. RESULTS: The full dataset and nested sample comprised 357,072 and
      54,602 individuals, respectively. Prevalence of hypertriglyceridemia, borderline
      high TG, high TG, very high TG, and severe hypertriglyceridemia in the full
      dataset was 29.2, 16.2, 12.9, 0.11, and 0.011%, respectively; corresponding rates
      in the nested sample were 19.0, 17.2, 0.25, and 0.016%, respectively. TG levels
      were 16.4% higher in males versus females; males had a greater risk of
      hypertriglyceridemia (risk ratio 1.25; 95% CI 1.24, 1.26; P < 0.0001). Prevalence
      of hypertriglyceridemia increased with age, peaking at 40-49 years in males
      (42.8%) and 60-69 years in females (34.4%); a 0.61% increase in TG levels for
      each year of life was predicted. Hypertriglyceridemia prevalence increased over
      time. Correlations between TG and LDL-C, HDL-C, TC, and HbA1c (nested sample
      only) were observed. CONCLUSIONS: Almost one-third of Russians have
      hypertriglyceridemia, but severe disease (TG >= 10.0 mmol/L) is rare. Although
      the risk of hypertriglyceridemia was greater in males versus females, its
      prevalence increased with age, regardless of sex. TG was associated with HbA1c,
      LDL-C, HDL-C, and TC.

PMID- 26303404
TI  - n-3 polyunsaturated fatty acids stimulate osteoclastogenesis through PPARgamma
      mediated enhancement of c-Fos expression, and suppress osteoclastogenesis through
      PPARgamma-dependent inhibition of NFkB activation.
AB  - n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) have been reported to suppress osteoclastogenesis in
      vivo. In this study, the effect of PUFAs on receptor for activation of nuclear
      factor-kappaB ligand (RANKL)-induced osteoclastogenesis was examined using bone
      marrow-derived monocytes/macrophage precursor cells (BMMs) or bone marrow cells
      (BMCs) in vitro. EPA and DHA stimulated the osteoclastic differentiation of BMMs,
      but n-6 PUFAs, linoleic acid and arachidonic acid had no effect. The stimulation
      of osteoclastogenesis of BMMs by EPA and DHA was associated with enhancement of
      the gene expressions of c-Fos, tartrate-resistant acid phosphatase, cathepsin K
      and peroxisome proliferator-activated receptor-gamma (PPARgamma) and the protein
      levels of c-Fos, PPARgamma and nuclear factor of activated T cells, cytoplasmic,
      calcineurin-dependent-1 (NFATc1). The PPARgamma agonists, rosiglitazone and
      GW1929, also stimulated the osteoclastogenesis of BMMs. The PPARgamma
      antagonists, T0070907 and GW9662, inhibited the stimulations of
      osteoclastogenesis and c-Fos expression by EPA or DHA. However, EPA and DHA
      inhibited the osteoclastogenesis in BMCs including BMMs and mesenchymal stem
      cells (MSCs). This inhibition was associated with suppression of the expression
      of RANKL and nuclear factor-kappaB (NFkappaB)-regulating genes, cyclooxygenase 2,
      TNFalpha and IL-6 in BMCs and MSCs. The agonists and antagonists of PPARgamma
      showed that the inhibitions of NFkappaB transcriptional activity and
      osteoclastogenesis by EPA and DHA were PPARgamma-dependent. These results suggest
      that EPA and DHA directly act on BMMs and stimulate osteoclastogenesis through
      enhancing c-Fos expression mediated by PPARgamma but suppress osteoclastogenesis
      through the PPARgamma-dependent inhibition of NFkappaB activation of MSCs in
      BMCs. 

PMID- 26303406
TI  - A large Great Britain-wide outbreak of STEC O157 phage type 8 linked to handling
      of raw leeks and potatoes - CORRIGENDUM.

PMID- 26303405
TI  - Resveratrol compounds inhibit human holocarboxylase synthetase and cause a lean
      phenotype in Drosophila melanogaster.
AB  - Holocarboxylase synthetase (HLCS) is the sole protein-biotin ligase in the human
      proteome. HLCS has key regulatory functions in intermediary metabolism, including
      fatty acid metabolism, and in gene repression through epigenetic mechanisms. The
      objective of this study was to identify food-borne inhibitors of HLCS that alter
      HLCS-dependent pathways in metabolism and gene regulation. When libraries of
      extracts from natural products and chemically pure compounds were screened for
      HLCS inhibitor activity, resveratrol compounds in grape materials caused an HLCS
      inhibition of >98% in vitro. The potency of these compounds was
      piceatannol>resveratrol>piceid. Grape-borne compounds other than resveratrol
      metabolites also contributed toward HLCS inhibition, e.g., p-coumaric acid and
      cyanidin chloride. HLCS inhibitors had meaningful effects on body fat mass. When
      Drosophila melanogaster brummer mutants, which are genetically predisposed to
      storing excess amounts of lipids, were fed diets enriched with grape leaf
      extracts and piceid, body fat mass decreased by more than 30% in males and
      females. However, Drosophila responded to inhibitor treatment with an increase in
      the expression of HLCS, which elicited an increase in the abundance of
      biotinylated carboxylases in vivo. We conclude that mechanisms other than
      inhibition of HLCS cause body fat loss in flies. We propose that the primary
      candidate is the inhibition of the insulin receptor/Akt signaling pathway. 

PMID- 26303408
TI  - Structures of G protein-coupled receptors reveal new opportunities for drug
      discovery.
AB  - X-ray structures of G protein-coupled receptors (GPCRs) have now been reported
      for more than 60 ligands and 20 receptors, including examples from GPCR classes
      A, B, C and F. The new structures show previously unobtainable details of
      interactions between GPCRs and ligands, including the roles of lipophilic regions
      and water molecules as key drivers of binding. In addition, the structures have
      revealed several surprising ligand-binding modes, including sites outside the
      orthosteric pocket. This new information is dramatically changing the way we
      approach GPCR drug discovery. 

PMID- 26303407
TI  - Cp/Heph mutant mice have iron-induced neurodegeneration diminished by
      deferiprone.
AB  - Brain iron accumulates in several neurodegenerative diseases and can cause
      oxidative damage, but mechanisms of brain iron homeostasis are incompletely
      understood. Patients with mutations in the cellular iron-exporting ferroxidase
      ceruloplasmin (Cp) have brain iron accumulation causing neurodegeneration. Here,
      we assessed the brains of mice with combined mutation of Cp and its homolog
      hephaestin. Compared to single mutants, brain iron accumulation was accelerated
      in double mutants in the cerebellum, substantia nigra, and hippocampus. Iron
      accumulated within glia, while neurons were iron deficient. There was loss of
      both neurons and glia. Mice developed ataxia and tremor, and most died by 9
      months. Treatment with the oral iron chelator deferiprone diminished brain iron
      levels, protected against neuron loss, and extended lifespan. Ferroxidases play
      important, partially overlapping roles in brain iron homeostasis by facilitating
      iron export from glia, making iron available to neurons. Above: Iron (Fe)
      normally moves from capillaries to glia to neurons. It is exported from the glia
      by ferroportin (Fpn) with ferroxidases ceruloplasmin (Cp) and/or Hephaestin
      (Heph). Below: In mice with mutation of Cp and Heph, iron accumulates in glia,
      while neurons have low iron levels. Both neurons and glia degenerate and mice
      become ataxic unless given an iron chelator.

PMID- 26303410
TI  - Autism Phenotypes in Tuberous Sclerosis Complex: Diagnostic and Treatment
      Considerations.
AB  - Tuberous sclerosis complex is a multisystem, chronic genetic condition
      characterized by systemic growth of benign tumors and often accompanied by
      epilepsy, autism spectrum disorders, and intellectual disability. Nonetheless,
      the neurodevelopmental phenotype of these patients is not often detailed. The
      authors describe 3 individuals with tuberous sclerosis complex who share common
      characteristics that can help to identify a distinct profile of autism spectrum
      disorder. These findings include typical cognitive development, expressive and
      pragmatic language deficits, and anxiety. The authors also describe features
      specific to tuberous sclerosis complex that require consideration before
      diagnosing an autism spectrum disorder. Identifying distinct profiles of autism
      spectrum disorder in tuberous sclerosis complex can help optimize treatment
      across the life span. 

PMID- 26303411
TI  - Epilepsy Following Neonatal Seizures Secondary to Hemorrhagic Stroke in Term
      Neonates.
AB  - Intracranial hemorrhage accounts for about 50% of all pediatric stroke. Studies
      of term infants with intracranial hemorrhage have shown favorable motor and
      cognitive outcome. The goal of this study was to examine the risk of developing
      epilepsy in full-term infants with intracranial hemorrhage. A retrospective study
      was performed of term neonates (greater than or equal to 37 weeks gestation) with
      intracranial hemorrhage and confirmed seizures. Fifteen patients with
      intracranial hemorrhage and neonatal seizures were identified. Four patients did
      not have follow-up information beyond the neonatal period (1 death, 3 lost to
      follow-up after initial clinic visit). The average follow-up period for the
      remaining 11 patients was approximately 22 months. Ten out of the 11 patients
      (91%) who were followed were seizure-free and off antiepileptic medications. One
      patient required a ventriculoperitoneal shunt and subsequently developed
      infantile spasms. The authors found that overall outcome was favorable with
      respect to development of epilepsy. 

PMID- 26303409
TI  - Cerebellar Development and Autism Spectrum Disorder in Tuberous Sclerosis
      Complex.
AB  - Approximately 50% of patients with the genetic disease tuberous sclerosis complex
      present with autism spectrum disorder. Although a number of studies have
      investigated the link between autism and tuberous sclerosis complex, the etiology
      of autism spectrum disorder in these patients remains unclear. Abnormal
      cerebellar function during critical phases of development could disrupt
      functional processes in the brain, leading to development of autistic features.
      Accordingly, the authors review the potential role of cerebellar dysfunction in
      the pathogenesis of autism spectrum disorder in tuberous sclerosis complex. The
      authors also introduce conditional knockout mouse models of Tsc1 and Tsc2 that
      link cerebellar circuitry to the development of autistic-like features. Taken
      together, these preclinical and clinical investigations indicate the cerebellum
      has a profound regulatory role during development of social communication and
      repetitive behaviors. 

PMID- 26303412
TI  - Isochromosome X in Myelodysplastic Syndrome.

PMID- 26303413
TI  - Inhibitors of serine proteases decrease sperm penetration during porcine
      fertilization in vitro by inhibiting sperm binding to the zona pellucida and
      acrosome reaction.
AB  - Serine proteases are involved in mammalian fertilization. Inhibitors of serine
      proteases can be applied to investigate at which point these enzymes exert their
      action. We selected two serine protease inhibitors, 4-(2
      aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF, 100 MUM) and soybean
      trypsin inhibitor (STI, 5 MUM) from Glycine max, via previous dose-response IVF
      experiments and sperm toxicity tests. In the present study, we evaluated how
      these inhibitors affect porcine fertilization in vitro as calculated on total
      fertilization rate, polyspermy rate, and the sperm number per fertilized oocyte
      of cumulus-intact, cumulus-free, and zona-free oocytes. In the control group (no
      inhibitor), these parameters were 86%, 49%, and 2.2 for cumulus-intact oocytes
      and 77%, 43%, and 2.2 for cumulus-free oocytes (6-hour gamete incubation period,
      1.25 * 10(5) spermatozoa/mL). 4-(2-Aminoethyl)benzenesulfonyl fluoride
      hydrochloride and STI significantly reduced total fertilization and polyspermy
      rate in cumulus-intact and cumulus-free oocytes (P < 0.05). Total fertilization
      rates were respectively 65% and 53% (AEBSF) and 36% and 17% (STI). Inhibition
      rates were higher in cumulus-free oocytes than in cumulus-intact oocytes,
      indicating that inhibitors exerted their action after sperm passage through the
      cumulus. 4-(2-Aminoethyl)benzenesulfonyl fluoride hydrochloride but not STI
      reduced sperm binding to the ZP. The acrosome reaction was significantly
      inhibited by both inhibitors. Only 40.4% (AEBSF) and 11.4% (STI) of spermatozoa
      completed a calcium-induced acrosome reaction compared to 86.7% of spermatozoa in
      the control group. There was no effect on sperm binding or fertilization
      parameters in zona-free oocytes. In conclusion, sperm-zona binding and acrosome
      reaction were inhibited by serine protease inhibitors during porcine IVF. 

PMID- 26303414
TI  - Efficacy and safety of oxytocin augmentation therapy for schizophrenia: an
      updated systematic review and meta-analysis of randomized, placebo-controlled
      trials.
AB  - The aim of this study was to perform a systematic review and an updated and
      comprehensive meta-analysis of oxytocin augmentation therapy in patients with
      schizophrenia who received antipsychotic agents. Data published up to 07/11/2015
      were obtained from PubMed, PsycINFO, and Cochrane Library databases. We conducted
      a systematic review and meta-analysis of patients' data from randomized
      controlled trials (RCTs) comparing oxytocin with placebo. Relative risk (RR),
      standardized mean difference (SMD), and 95 % confidence intervals (95 % CI) based
      on the random-effects model were calculated. We included seven RCTs; the total
      sample size was 206 patients. Oxytocin was superior to placebo for decreasing the
      Positive and Negative Syndrome Scale (PANSS) general subscale scores (SMD = 
      0.44, 95 % CI -0.82 to -0.06, p = 0.02, I (2) = 0 %, N = 4, n = 112); however, it
      was not different from placebo for total symptoms (SMD = -0.46, 95 % CI -1.20 to
      0.28, p = 0.22, I (2) = 80 %, N = 6, n = 162), positive symptoms (SMD = -0.18, 95
      % CI -0.87 to 0.51, p = 0.60, I (2) = 81 %, N = 6, n = 192), and negative
      symptoms (SMD = -0.34, 95 % CI -0.76 to 0.08, p = 0.12, I (2) = 55 %, N = 7, n =
      214). However, a sensitivity analysis including only oxytocin administration on
      consecutive days studies was superior to placebo in negative symptoms (SMD = 
      0.44, 95 % CI -0.87 to -0.01, p = 0.04, I (2) = 51 %, N = 6 n = 192). There were
      no significant differences for all-cause discontinuation (RR = 1.02) and
      individual side effects such as headache and dizziness between oxytocin and
      placebo. Oxytocin may improve PANSS general subscale scores in schizophrenia and
      seems to be well tolerated. However, because the number of studies in the current
      analysis was small, further study will be required using larger sample sizes. 

PMID- 26303416
TI  - Epigenetic control of cardiovascular health by nutritional polyphenols involves
      multiple chromatin-modifying writer-reader-eraser proteins.
AB  - Nowadays, epigenetic mechanisms involving DNA methylation, histone modifications
      and microRNA regulation emerge as important players in cardiovascular disease
      (CVD). Epigenetics may provide the missing link between environment, genome and
      disease phenotype and be responsible for the strong interindividual variation in
      disease risk factors underlying CVD. Daily diet is known to have a major
      influence on both the development and the prevention of CVD. Interestingly, the
      dietary lifestyle of our (grand)parents and of us contributes to CVD risk by
      metabolic (re)programming of our epigenome in utero, after birth or during life.
      In contrast to genetic mutations, the plasticity of CVD related epigenetic
      changes makes them attractive candidates for nutritional prevention or
      pharmacological intervention. Although a growing number of epidemiologic studies
      have shown a link between the ingestion of nutritional polyphenols and
      cardiovascular health benefits, potential involvement of epigenetic mechanisms
      has been underexplored. In this review, we will give an overview of epigenetic
      alterations in atherosclerosis, with the focus on DNA and histone modifications
      by chromatin-modifying proteins. Finally, we illustrate that cocoa flavanols and
      other classes of dietary molecules may promote cardiovascular health by targeting
      multiple classes of chromatin writer-reader-eraser proteins related to histone
      acetylation-methylation and DNA methylation. 

PMID- 26303415
TI  - Reduction in hospitalisations and emergency department visits for frail patients
      with heart failure: Results of the UMIPIC healthcare programme.
AB  - OBJECTIVES: Heart failure (HF) is a disease with high morbidity and mortality. We
      evaluated the usefulness of the Comprehensive Management Units for Patients with
      HF (Unidades de Manejo Integral para Pacientes con IC [UMIPIC]) programme.
      PATIENTS AND METHOD: We analysed the patient data from the UMIPIC programme,
      which was recorded in the HF registry (RICA) of the Spanish Society of Internal
      Medicine. We compared emergency department visits and hospitalisations for any
      cause and for HF during the year prior to inclusion in the programme against
      those that occurred during the subsequent follow-up year, using the chi-squared
      test. RESULTS: A total of 258 patients (mean age, 80years; 51.9% women) were
      included in the study. During the previous year, there were 693 hospitalisations
      for all causes and 174 hospitalisations during the follow-up (75% reduction,
      P<.001). There were 613 hospitalisations for HF during the previous year and 92
      during the follow-up (85% reduction, P<.001); 655 vs. 302 in terms of emergency
      department visits for any cause (53.9% reduction, P<.001); and 440 vs. 120 for
      emergency department visits for HF (72% reduction, P<.001). There were no
      significant differences in the number of hospitalisations or emergency department
      visits for causes other than HF. CONCLUSIONS: The UMIPIC programme based on the
      comprehensive care of elderly patients with HF and comorbidity reduces the rate
      of hospital readmissions and emergency department visits during the first year of
      follow-up.

PMID- 26303417
TI  - DNA Methyltransferases Inhibitors from Natural Sources.
AB  - DNA methyltransferases (DNMTs) catalyze the methylation at cytosine-C5 mainly in
      a CpG dinucleotide context. Although DNA methylation is essential for fundamental
      processes like embryonic development or differentiation, aberrant expression
      and/or activities of DNMTs are involved in several pathologies, from
      neurodegeneration to cancer. DNMTs inhibition can arrest tumor growth, cells
      invasiveness and induce differentiation, whereas their increased expression is
      shown in numerous cancer types. Moreover, hypermethylated promoters of tumor
      suppressor genes lead to their silencing. Hence, the use of specific inhibitors
      of DNMT might reactivate those genes and stop or even reverse the aberrant cell
      processes. To date, the only approved DNMTs inhibitors for therapy belong to the
      nucleoside-based family of drugs, but they display relevant side effects as well
      as high chemical instability. Thus, there is a keen interest actually exists to
      develop novel, potent and safe inhibitors possessing a nonnucleoside structure.
      Increasing literature evidence is highlighting that natural sources could help
      the researchers to achieve this goal. Indeed, several polyphenols, flavonoids,
      antraquinones, and others are described able to inhibit DNMTs activity and/or
      expression, thus decreasing the methylation/silencing of different genes involved
      in tumorigenesis. These events can lead to re-expression of such genes and to
      cell death in diverse cancer cell lines. Epigallocatechin-3-gallate (1) and
      laccaic acid A (11) resulted the most effective DNMT1 inhibitors with
      submicromolar IC50 values, acting as competitive inhibitors. Compound 1 and 11
      both displayed gene demethylation and re-activation in several cancers. However,
      all of the natural compounds described in this review showed important results,
      from gene reactivation to cell growth inhibition. Moreover, some of them
      displayed interesting activity even in rodent cancer models and very recently
      entered clinical trials.

PMID- 26303418
TI  - Epigenetic alterations as a universal feature of cancer hallmarks and a promising
      target for personalized treatments.
AB  - Despite considerable scientific progress, the burden of cancer in our society
      remains a major public health problem. Tumorigenesis is recognized as a complex
      and multistep process that involves the accumulation of successive
      transformational events with multi-factorial etiology. Nevertheless, such events
      result in the acquisition of key hallmark characteristics that are shared by all
      cancer cells. Accumulating evidence indicates that, besides genetic alterations,
      epigenetic mechanisms (heritable changes in gene expression caused by
      modifications in chromatin structure without alterations of DNA sequence) are
      implicated in the acquisition of malignant phenotype. The potential reversibility
      of epigenetic alterations linked to tumorigenesis offers a promising avenue for
      therapeutic intervention. This review focuses on the epigenetic regulation of the
      cancer hallmarks and the foreseeable use of epigenetic drugs to target these
      features as a promising strategy for anti-cancer therapy. Based on this body of
      evidence, we believe that epigenetic deregulations can affect virtually all cell
      functions and therefore therapeutic approaches with epigenetic drugs could allow
      multi-target approach against the hallmarks of cancer. 

PMID- 26303419
TI  - Improvement of malignant pleural mesothelioma immunotherapy by epigenetic
      modulators.
AB  - In the absence of a satisfactory treatment of malignant pleural mesothelioma
      (MPM), novel therapeutic strategies are urgently needed. Among these,
      immunotherapy offers a series of advantages such as tumor specificity and good
      tolerability. Unfortunately, MPM immunotherapy is frequently limited by
      incomplete cell differentiation or feedback loop regulatory mechanisms. In this
      review, we describe different components of the innate immune system and discuss
      strategies to improve MPM immunotherapy by using epigenetic modulators. 

PMID- 26303420
TI  - Role of Histone Acetylation in Cell Cycle Regulation.
AB  - Core histone acetylation is a key prerequisite for chromatin decondensation and
      plays a pivotal role in regulation of chromatin structure, function and dynamics.
      The addition of acetyl groups disturbs histone/DNA interactions in the nucleosome
      and alters histone/histone interactions in the same or adjacent nucleosomes.
      Acetyl groups can also provide binding sites for recruitment of bromodomain (BRD)
      containing non-histone readers and regulatory complexes to chromatin allowing
      them to perform distinct downstream functions. The presence of a particular
      acetylation pattern influences appearance of other histone modifications in the
      immediate vicinity forming the "histone code". Although the roles of the
      acetylation of particular lysine residues for the ongoing chromatin functions is
      largely studied, the epigenetic inheritance of histone acetylation is a debated
      issue. The dynamics of local or global histone acetylation is associated with
      fundamental cellular processes such as gene transcription, DNA replication, DNA
      repair or chromatin condensation. Therefore, it is an essential part of the
      epigenetic cell response to processes related to internal and external signals. 

PMID- 26303422
TI  - Current Advances in the Identification and Characterization of Putative Drug and
      Vaccine Targets in the Bacterial Genomes.
AB  - The development in sequencing technologies over the past few decades have
      increased the pace of decoding genetic and functional information present in the
      genomes of pathogenic microorganisms. The knowledge obtained through sequencing
      projects facilitated the identification of genes that codes for virulence
      factors. A major portion of genomes of pathogenic of bacteria contains genes
      which are classified as "hypothetical or uncharacterized". Due to unavailability
      of precise information about the functionality of these genes, the pathogenic
      mechanisms utilized by varieties of microorganisms are not fully understood. This
      respective class of proteins draws a significant interest of pharmaceutical
      research as they have potential to provide new clues regarding the development of
      novel therapeutics particularly against the multidrug resistant strains of
      bacteria. The in silico identification of putative drug and vaccine targets in
      the set of uncharacterized proteins through comparative and subtractive genome
      analyses facilitates the increase usability and efficiency of the present drugs.
      The functional annotation of these characterized target proteins can uncover
      varieties of biochemical pathways important for the survival and pathogenesis of
      bacteria. This review focuses on the current protocols available for
      identification and functional annotations of these uncharacterized potential
      therapeutic targets. 

PMID- 26303423
TI  - Biopolymer-Based Delivery Systems: Challenges and Opportunities.
AB  - Biopolymer-based nanostructures or microstructures can be fabricated with
      different compositions, structures, and properties so that colloidal delivery
      systems can be tailored for specific applications. These structures can be
      assembled using various approaches, including electrospinning, coacervation,
      nanoprecipitation, injection, layer-by-layer deposition, and/or gelation. A major
      application of biopolymer-based particles is to encapsulate, protect, and release
      active molecules in the agricultural, food, supplements, personal care, and
      pharmaceutical sectors. The inherent variability and complexity of biopolymers
      (proteins and polysaccharides) often makes it challenging to produce particles
      with well-defined physicochemical and functional attributes. In this review, we
      discuss the properties of biopolymers, common particle fabrication methods, and
      some of the major challenges and opportunities associated with developing
      biopolymer-based particles for application as food-grade delivery systems. 

PMID- 26303424
TI  - Designing Prodrugs Based on Special Residues of Human Serum Albumin.
AB  - Human serum albumin (HSA) is the most abundant protein in the plasma. HSA plays a
      central role in drug pharmacokinetics because most drugs bound to HSA are
      delivered to their target organ/tissues. The prodrug strategies have shown great
      promise for improving the activity and selectivity of drugs. Designing prodrugs
      based on special HSA residues, such as Cys34 and Lys residues, has been
      extensively studied. Therefore, this review provides an overview of the
      development of nonsteroidal anti-inflammatory and anticancer prodrugs based on
      these special residues. In conclusion, this review may guide the rational design
      and development of new prodrugs for future clinical applications. 

PMID- 26303425
TI  - Computational Sampling and Simulation Based Assessment of Novel Mycobacterium
      tuberculosis Glutamine Synthetase Inhibitors: Study Involving Structure Based
      Drug Design and Free Energy Perturbation.
AB  - The highly persistent nature of Mycobacterium tuberculosis can be attributed to
      its lipophilic cell wall which acts as a major barrier in the process of drug
      discovery against tuberculosis. Glutamine synthetase plays a major role in
      nitrogen metabolism and cell wall biosynthesis of pathogenic mycobacteria. The
      current review focuses on the structural and functional aspects of Mtb glutamine
      synthetase and an overview of its reported inhibitors till date. Also in the
      present study, we employed a computational structure based drug design protocol
      for identifying novel inhibitors against Mtb glutamine synthetase (MtbGS). A
      total of 12 hits were identified based on e-pharmacophore related search and
      virtual screening, which were further tested for their in vitro MtbGS inhibitory
      activity. Three compounds (compound 6, 1 and 12) were found with IC50 less than 5
      &#181;M, of which compound 6 being top active with IC50 of 2.124 &#181;M.
      Differential scanning fluorimetry studies were employed so as to measure the
      thermal stability of the protein complexed with the most active compound. Also
      the protein complexes with top three active compounds were subjected for
      molecular dynamics simulations to study their binding pattern and stabilization
      effect. The solvation free energies were also determined for these compounds,
      undertaking free energy perturbation studies, which can be used further for lead
      optimization in the process of anti-tubercular drug discovery targeting Mtb
      glutamine synthetase. 

PMID- 26303426
TI  - Inhibition of Shikimate Kinase and Type II Dehydroquinase for Antibiotic
      Discovery: Structure-Based Design and Simulation Studies.
AB  - The loss of effectiveness of current antibiotics caused by the development of
      drug resistance has become a severe threat to public health. Current widely used
      antibiotics are surprisingly targeted at a few bacterial functions - cell wall,
      DNA, RNA, and protein biosynthesis - and resistance to them is widespread and
      well identified. There is therefore great interest in the discovery of novel
      drugs and therapies to tackle antimicrobial resistance, in particular drugs that
      target other essential processes for bacterial survival. In the past few years a
      great deal of effort has been focused on the discovery of new inhibitors of the
      enzymes involved in the biosynthesis of aromatic amino acids, also known as the
      shikimic acid pathway, in which chorismic acid is synthesized. The latter
      compound is the synthetic precursor of L-Phe, L-Tyr, L-Phe, and other important
      aromatic metabolites. These enzymes are recognized as attractive targets for the
      development of new antibacterial agents because they are essential in important
      pathogenic bacteria, such as Mycobacterium tuberculosis and Helicobacter pylori,
      but do not have any counterpart in human cells. This review is focused on two key
      enzymes of this pathway, shikimate kinase and type II dehydroquinase. An overview
      of the use of structure-based design and computational studies for the discovery
      of selective inhibitors of these enzymes will be provided. A detailed view of the
      structural changes caused by these inhibitors in the catalytic arrangement of
      these enzymes, which are responsible for the inhibition of their activity, is
      described. 

PMID- 26303427
TI  - Structure-Based Design of Inhibitors of the Crucial Cysteine Biosynthetic Pathway
      Enzyme O-Acetyl Serine Sulfhydrylase.
AB  - The cysteine biosynthetic pathway is of fundamental importance for the growth,
      survival, and pathogenicity of the many pathogens. This pathway is present in
      many species but is absent in mammals. The ability of pathogens to counteract the
      oxidative defences of a host is critical for the survival of these pathogens
      during their long latent phases, especially in anaerobic pathogens such as
      Entamoeba histolytica, Leishmania donovani, Trichomonas vaginalis, and Salmonella
      typhimurium. All of these organisms rely on the de novo cysteine biosynthetic
      pathway to assimilate sulphur and maintain a ready supply of cysteine. The de
      novo cysteine biosynthetic pathway, on account of its being important for the
      survival of pathogens and at the same time being absent in mammals, is an
      important drug target for diseases such as amoebiasis, trichomoniasis &
      tuberculosis. Cysteine biosynthesis is catalysed by two enzymes: serine acetyl
      transferase (SAT) followed by O-acetylserine sulfhydrylase (OASS). OASS is well
      studied, and with the availability of crystal structures of this enzyme in
      different conformations, it is a suitable template for structure-based inhibitor
      development. Moreover, OASS is highly conserved, both structurally and sequence
      wise, among the above-mentioned organisms. There have been several reports of
      inhibitor screening and development against this enzyme from different organisms
      such as Salmonella typhimurium, Mycobacterium tuberculosis and Entamoeba
      histolytica. All of these inhibitors have been reported to display micromolar to
      nanomolar binding affinities for the open conformation of the enzyme. In this
      review, we highlight the structural similarities of this enzyme in different
      organisms and the attempts for inhibitor development so far. We also propose that
      the intermediate state of the enzyme may be the ideal target for the design of
      effective highaffinity inhibitors. 

PMID- 26303421
TI  - Histone and Non-Histone Targets of Dietary Deacetylase Inhibitors.
AB  - Acetylation is an important, reversible post-translational modification affecting
      histone and non-histone proteins with critical roles in gene transcription, DNA
      replication, DNA repair, and cell cycle progression. Key regulatory enzymes
      include histone deacetylase (HDACs) and histone acetyltransferases (HATs).
      Overexpressed HDACs have been identified in many human cancers, resulting in
      repressed chromatin states that interfere with vital tumor suppressor functions.
      Inhibition of HDAC activity has been pursued as a mechanism for re-activating
      repressed genes in cancers, with some HDAC inhibitors showing promise in the
      clinical setting. Dietary compounds and their metabolites also have been shown to
      modulate HDAC activity or expression. Out of this body of research, attention
      increasingly has shifted towards non-histone targets of HDACs and HATs, such as
      transcriptions factors, hormone receptors, DNA repair proteins, and cytoskeletal
      components. These aspects are covered in present review, along with the possible
      clinical significance. Where such data are available, examples are cited from the
      literature of studies with short chain fatty acids, polyphenols, isoflavones,
      indoles, organosulfur compounds, organoselenium compounds, sesquiterpene
      lactones, isoflavones, and various miscellaneous agents. By virtue of their
      effects on both histone and non-histone proteins, dietary chemopreventive agents
      modulate the cellular acetylome in ways that are only now becoming apparent. A
      better understanding of the molecular mechanisms will likely enhance the
      potential to more effectively combat diseases harboring altered epigenetic
      landscapes and dysregulated protein signaling. 

PMID- 26303428
TI  - Recent Advances in Computer-Assisted Structure-Based Identification and Design of
      Histone Deacetylases Inhibitors.
AB  - Aberrant epigenetic control is a common phenomenon in tumour progression. The
      epigenetic modifications such as DNA methylation, histone modification and
      nucleosome remodelling are involved in the regulation of many biological
      processes, alteration in which can result into tumourogenesis. Histone
      acetylation is often associated with gene expression; however deacetylated
      histones generally results in gene suppression. This whole reversible process is
      mediated by Histone acetyltranferase and Histone deacetylases (HDACs)
      respectively. HDACs perform the deacetylation of histones in nucleosomes, which
      intervenes changes in chromatin remodelling, prompting regulation of gene
      expression. HDACs likewise direct the acetylation status of various other non
      histone substrates that includes oncogenes and tumour silencing proteins. As HDAC
      inhibition induces various tumour cells to enter apoptosis and consequently cell
      cycle arrest therefore, a large number of HDAC inhibitors have been reported to
      develop as a new class of anti-cancer agents. Apart from the two existing FDA
      approved HDAC inhibitors- Varinostat and Depsipetide, recently a new drug Farydak
      has been approved by the FDA for the treatment of multiple myeloma which thus
      validated the use of HDAC inhibitors for the treatment of cancer. Also, several
      other HDAC inhibitors are undergoing clinical trials. Here, we have reviewed the
      current status of structure based computational studies that has helped to
      rationalize the successful identification of HDAC inhibitors. The objective of
      the present review is to provide an overview of contribution of structure-based
      computational studies that have helped in identifying HDAC inhibitors with an
      emphasis on the perspectives of its insight, current status, advances and future
      opportunities as well as the evolving efforts to characterize the structural
      dynamics of HDACs. 

PMID- 26303429
TI  - Structure-Based Discovery of PDEs Inhibitors.
AB  - Phosphodiesterases (PDEs) catalyze the hydrolysis of cAMP and cGMP, thereby
      regulating the cyclic nucleotide signalling pathways and biological responses.
      PDEs inhibitors can be used clinically for treatment of several diseases
      including central nervous system disorders, erectile dysfunction, pulmonary
      hypertension, acute refractory cardiac failure, and inflammatory diseases such as
      chronic obstructive pulmonary disease. However, the unfavourable risk-benefit
      ratio and side-effect profiles of non-selective PDEs inhibitors have impeded
      their therapeutic success and therefore spurred the pharmaceutical industry to
      develop family-selective PDE inhibitors. Given the recent remarkable advances in
      structure-based drug design, this review will summarize developments and
      achievements in structure-based search, design and optimization of PDEs
      inhibitors, and highlight the challenges that need to be addressed. 

PMID- 26303430
TI  - Advances in Computational Structure-Based Drug Design and Application in Drug
      Discovery.
AB  - Compared with the increasing and widespread bacterial resistance to clinical
      medicines and the urgent need for cures of intractable diseases, there is a
      dramatic decline in the numbers of drugs reaching the market or clinical trials.
      Accordingly, it has become imperative to discover more rational and efficient
      strategies to design and develop novel drugs. Structure-based drug
      design/discovery (SBDD) is one of the computer-aided methods, by which novel
      drugs are designed or discovered based on the knowledge of 3D structures of the
      relevant specific targets. During the past few decades, the great potentials and
      success of SBDD have been seen in the field of drug discovery. In this review, we
      present an overview of the key mechanisms of SBDD, the frequently used computer
      programs in SBDD and the reported successful cases. Finally, several typical
      design processes of lead components from SBDD are also highlighted in detail,
      such as the discovery of inhibitors of G protein-coupled receptors (GPCRs),
      antibacterial drugs, and anti-cancer drugs. 

PMID- 26303431
TI  - In vitro refolding and functional analysis of polyhistidine-tagged Buthus
      martensii Karsch antitumor-analgesic peptide produced in Escherichia coli.
AB  - OBJECTIVES: To identify an efficient in vitro refolding method to generate highly
      active His6-tagged scorpion toxin antitumor-analgesic peptide (AGAP) isolated
      from Escherichia coli inclusion bodies. RESULTS: N- and C-Terminal His6-tagged
      recombinant (r) AGAP (NHis6-rAGAP and CHis6-rAGAP, respectively) were expressed
      in E. coli; the purification and refolding conditions were optimized. CHis6
      rAGAP, but not NHis6-rAGAP, exhibited significant in vitro antihepatoma activity
      that was much greater than that of rAGAP produced using SUMO fusion technology
      (IC50, 0.4 +/- 0.08 vs. 1.8 +/- 0.3 MUM). CHis6-rAGAP also showed significant
      inhibition of tumor growth in a mouse xenograft model of human hepatoma and
      inhibition of neuronal excitability, demonstrated by blockage of voltage
      sensitive tetrodotoxin-resistant (TTX-R) sodium currents in acute isolated dorsal
      root ganglion neurons. CONCLUSIONS: This refolding protocol optimized for C
      terminal His6-tagged scorpion rAGAP is potentially applicable to similar long
      chain and cysteine-rich toxins.

PMID- 26303432
TI  - In vivo repair of rat transected sciatic nerve by low-intensity pulsed ultrasound
      and induced pluripotent stem cells-derived neural crest stem cells.
AB  - OBJECTIVES: To evaluate the effects of the combination of low-intensity pulsed
      ultrasound (LIPUS) and induced pluripotent stem cells-derived neural crest stem
      cells (iPSCs-NCSCs) on the regeneration of rat transected sciatic nerve in vivo.
      RESULTS: Tissue-engineered tubular nerve conduit was fabricated by
      electrospinning aligned nanofibers in longitudinal direction. This sustained the
      iPSCs-NCSCs and could be used as a bridge in rat transected sciatic nerve.
      Treatment with 0.3 W cm(-2) LIPUS for 2 weeks and 5 min per day significantly
      improved the sciatic functional index, static sciatic function index and nerve
      conduction velocity of rat sciatic nerve. Histological analysis showed that there
      were more regenerative new blood vessels and new neurofilaments, higher
      expression level of beta-III tubulin (Tuj1) in the experimental group seeded with
      iPSCs-NCSCs and stimulated with LIPUS. CONCLUSION: Combination of LIPUS with
      iPSCs-NCSCs promoted the regeneration and reconstruction of rat transected
      sciatic nerve and is an efficient and cost-effective method for peripheral nerve
      regeneration.

PMID- 26303433
TI  - Genome-wide association study of the five-factor model of personality in young
      Korean women.

PMID- 26303434
TI  - Using Information and Communication Technologies for Family Communication and Its
      Association With Family Well-Being in Hong Kong: FAMILY Project.
AB  - BACKGROUND: Family communication is central to the family and its functioning. It
      is a mutual process in which family members create, share, and regulate meaning.
      Advancement and proliferation of information and communication technologies
      (ICTs) continues to change methods of family communication. However, little is
      known about the use of different methods for family communication and the
      influence on family well-being. OBJECTIVE: We investigated the sociodemographic
      factors associated with different methods of family communication and how they
      are associated with perceived family harmony, happiness, and health (3Hs) among
      Chinese adults in Hong Kong. METHODS: Data came from a territory-wide probability
      based telephone survey using the Family and Health Information Trend survey
      (FHInTs). Frequency of family communication using different methods (ie, face-to
      face, phone, instant messaging [IM], social media sites, and email) were recoded
      and classified as frequent (always/sometimes) and nonfrequent (seldom/never) use.
      Family well-being was measured using 3 questions of perceived family harmony,
      happiness, and health with higher scores indicating better family well-being.
      Adjusted odds ratios for family communication methods by sociodemographic
      characteristics and adjusted beta coefficients for family well-being by
      communication methods were calculated. RESULTS: A total of 1502 adults were
      surveyed. Face-to-face (94.85%, 1408/1484) was the most frequent means of
      communication followed by phone (78.08%, 796/1484), IM (53.64%, 796/1484), social
      media sites (17.60%, 261/1484), and email (13.39%, 198/1484). Younger age was
      associated with the use of phone, IM, and social media sites for family
      communication. Higher educational attainment was associated with more frequent
      use of all modes of communication, whereas higher family income was only
      significantly associated with more frequent use of IM and email (P=.001). Face-to
      face (beta 0.65, 95% CI 0.33-0.97) and phone use (beta 0.20, 95% CI 0.02-0.38)
      for family communication were associated with significantly higher levels of
      perceived family well-being. CONCLUSIONS: Socioeconomic disparities in using
      these information and communication technologies (ICT) methods for family
      communication were observed. Although traditional methods remain as the main
      platform for family communication and were associated with better family well
      being, a notable proportion of respondents are using new ICT methods, which were
      not associated with perceived family well-being. Because ICTs will continue to
      diversify modes of family communication, more research is needed to understand
      the impact of ICTs on family communication and well-being.

PMID- 26303435
TI  - Determinants of Private Long-Term Care Insurance Purchase in Response to the
      Partnership Program.
AB  - OBJECTIVE: To assess three possible determinants of individuals' response in
      their private insurance purchases to the availability of the Partnership for Long
      Term Care (PLTC) insurance program: bequest motives, financial literacy, and
      program awareness. DATA SOURCES: The health and retirement study (HRS) merged
      with data on states' implementation of the PLTC program. STUDY DESIGN: Individual
      level decision on private long-term care insurance is regressed on whether the
      PLTC program is being implemented for a given state-year, asset dummies, policy
      determinant variable, two-way and three-way interactions of these variables, and
      other controls, using fixed effects panel regression. DATA EXTRACTION METHODS:
      Analysis used a sample between 50 and 69 years of age from 2002 to 2010,
      resulting in 12,695 unique individuals with a total of 39,151 observations.
      PRINCIPAL FINDINGS: We find mild evidence that intent to bequest influences
      individual purchase of insurance. We also find that program awareness is
      necessary for response, while financial literacy notably increases
      responsiveness. CONCLUSIONS: Increasing response to the PLTC program among the
      middle class (the stated target group) requires increased efforts to create
      awareness of the program's existence and increased education about the program's
      benefits, and more generally, about long-term care risks and needs.

PMID- 26303436
TI  - Development and Characterization of an Engraftable Tissue-Cultured Skin
      Autograft: Alternative Treatment for Severe Electrical Injuries.
AB  - BACKGROUND/AIMS: Optimizing the treatment regimens of extensive or nonhealing
      defects is a constant challenge. Tissue-cultured skin autografts may be an
      alternative to mesh grafts and keratinocyte suspensions that are applied during
      surgical defect coverage. METHODS: Autologous epidermal and dermal cells were
      isolated, in vitro expanded and seeded on collagen-elastin scaffolds. The
      developed autograft was immunohistochemically and electron microscopically
      characterized. Subsequently, it was transplanted onto lesions of a severely
      burned patient. RESULTS: Comparability of the skin equivalent to healthy human
      skin could be shown due to the epidermal strata, differentiation, proliferation
      markers and development of characteristics of a functional basal lamina.
      Approximately 2 weeks after skin equivalent transplantation the emerging new skin
      correlated closely to the adjacent normal skin. CONCLUSION: The present study
      demonstrates the comparability of the developed organotypic skin equivalent to
      healthy human skin and its versatility for clinical applications.

PMID- 26303440
TI  - Synthesis of phenanthrene derivatives by intramolecular cyclization utilizing the
      [1,2]-phospha-Brook rearrangement catalyzed by a Bronsted base.
AB  - The synthesis of functionalized phenanthrene derivatives was achieved by
      intramolecular cyclization utilizing the [1,2]-phospha-Brook rearrangement under
      Bronsted base catalysis. Treatment of biaryl compounds having an alpha-ketoester
      moiety and an alkyne moiety at the 2 and 2' positions, respectively, with
      diisopropyl phosphite in the presence of a catalytic amount of phosphazene base
      P2-tBu provides 9,10-disubstituted phenanthrene derivatives in high yields. This
      reaction involves the generation of an ester enolate through an umpolung process,
      that is, addition of diisopropyl phosphite to a keto moiety followed by the [1,2]
      phospha-Brook rearrangement, the intramolecular addition to an alkyne, and the
      [3,3] rearrangement of the allylic phosphate moiety in a consecutive fashion. 

PMID- 26303437
TI  - The maize transcription factor EREB58 mediates the jasmonate-induced production
      of sesquiterpene volatiles.
AB  - Over the past two decades, Zea mays (maize) has been established as a model
      system for the study of indirect plant defense against herbivores. When attacked
      by lepidopteran larvae, maize leaves emit a complex blend of volatiles, mainly
      composed of sesquiterpenes, to attract the natural enemies of the herbivores.
      This is associated with a swift transcriptional induction of terpene synthases
      such as TPS10; however, the molecular components controlling the complex
      transcriptional reprogramming in this process are still obscure. Here, by
      exploiting the finding that the maize TPS10 promoter retained its full
      responsiveness to herbivory in Arabidopsis, we identified the region from -300 to
      -200 of the TPS10 promoter as both necessary and sufficient for its herbivore
      inducibility through 5' deletion mapping. A high-throughput screening of an
      Arabidopsis transcription factor library using this promoter region as the bait
      identified seven AP2/ERF family transcription factors. Among their close homologs
      in maize, EREB58 was the only gene responsive to herbivory, with a spatiotemporal
      expression pattern highly similar to that of TPS10. Meanwhile, EREB58 was also
      responsive to Jasmonate. In vivo and in vitro assays indicated that EREB58
      promotes TPS10 expression by directly binding to the GCC-box within the region
      from -300 to -200 of the TPS10 promoter. Transgenic maize plants overexpressing
      EREB58 constitutively over-accumulate TPS10 transcript, and also (E)-beta
      farnesene and (E)-alpha-bergamotene, two major sesquiterpenes produced by TPS10.
      In contrast, jasmonate induction of TPS10 and its volatiles was abolished in
      EREB58-RNAi transgenic lines. In sum, these results demonstrate that EREB58 is a
      positive regulator of sesquiterpene production by directly promoting TPS10
      expression. 

PMID- 26303443
TI  - Internet-based information about eye conditions for patients could be improved
      and used more.

PMID- 26303444
TI  - Current and predicted demographics of high myopia and an update of its associated
      pathological changes.
AB  - PURPOSE: Excessive axial elongation of the eye in high myopia can cause
      biomechanical stretching leading to various ocular complications. The purpose of
      this review is to provide an update on various pathologic changes, especially in
      the chorio-retina and sclera that have been reported recently using advanced
      ophthalmic bio-imaging modalities such as optical coherence tomography, magnetic
      resonance imaging and fundus photography. RECENT FINDINGS: The prevalence rates
      of pathologic myopia (myopic retinopathy and maculopathy) mirror the prevalence
      rates of high myopia as the risks of pathologic myopia increase with high myopia.
      Peripapillary and sub-foveal choroidal thinning, scleral thinning, and
      deformed/irregular eye shapes were found to be strongly associated with various
      pathologic myopic lesions, especially with posterior staphyloma and chorio
      retinal atrophy. Considering the increasing prevalence rate of myopia and
      pathologic myopia, these degenerative changes are likely to increase dramatically
      over the next few decades due to the rapid growth in the number of individuals
      with high myopia and the ageing population. SUMMARY: The current prevalence rates
      of pathologic myopia in older adults might have significantly underestimated the
      future prevalence rates and warrants age of onset of myopia being considered a
      major risk factor for pathologic myopia. Using advanced technology,
      identification of novel quantifiable chorio-retinal and scleral parameters in
      pathologic myopia would help to identify people at risk of developing pathologic
      myopia and potentially may revolutionise the management of myopia especially in
      risk prognostication and monitoring of disease progression.

PMID- 26303445
TI  - Microfluctuations in accommodation: an update on their characteristics and
      possible role.
AB  - PURPOSE: Following the recognition, some 80 years ago, that the accommodation of
      the eye is not stable but fluctuates over a range of about +/-0.5 D, mainly at
      frequencies of up to a few Hz, there has been a continuing interest in the
      characteristics of these microfluctuations (MFs) and their possible role in the
      control of accommodation. This paper reviews relevant work carried out since
      1988, when we previously reviewed the same topic (Charman WN, Heron G.
      Fluctuations in accommodation: a review. Ophthalmic Physiol Opt 1988; 8: 153
      164). RECENT FINDINGS: Studies relating to the effects on the MFs of stimulus
      form, luminance and vergence are described, together with those of pupil
      diameter, age and ametropia. Important advances in the understanding of the links
      between the characteristics of the MFs and those of the cardiopulmonary system,
      higher-order aberrations and ocular depth-of-focus are outlined. Only limited
      progress has been made in understanding the role of MFs in accommodation control.
      SUMMARY: While the dependence of the characteristics of the MFs in relation to
      observing conditions is now reasonably well understood, their involvement in
      accommodation control still needs clarification. The current consensus appears to
      be that any role is more likely to be concerned with maintaining an appropriate
      response, rather than in initiating responses to abrupt changes in stimulus
      vergence. Fluctuations at lower temporal frequencies (<0.6 Hz) are probably
      important to the control process, which may make use of the associated changes in
      the contrast and spatial frequency spectrum of the retinal image.

PMID- 26303446
TI  - IURead: a new computer-based reading test.
AB  - PURPOSE: To develop a computer-based single sentence reading test especially
      designed for clinical research enabling multiple repeat trials without reusing
      the same sentences. METHODS: We initially developed 422 sentences, with an
      average of 60 characters and 12 words. Presentation controls were improved by
      employing computer-based testing and the oral reading was recorded by visual
      inspection of digital audio recordings. Variability in reading speed of normally
      sighted adults between sentences, between charts, between subjects, between
      formats, and between display devices was quantified. The impact of display size
      and pixel resolution on test geometry was assessed, and the impact of reduced
      retinal image quality and retinal illuminance were compared for reading and
      standard letter acuities. Eleven visually normal subjects (age: 18-60 years)
      participated in this study. RESULTS: Stopwatch timing of sentences reliably
      underestimated reading times by about 0.3 s, and exhibited coefficients of
      repeatability 17 times larger than those estimated from visual inspection of
      digital recordings. A slight relaxing of the lexical content constraints had no
      effect on reading speed; neither did sentence format (single vs three lines) or
      display size or distance. Within subject standard deviations of reading speed for
      different sentences were small (between 6% and 9% of the mean speed) requiring
      only small samples sizes to achieve typical statistical reliability and power
      when comparing conditions within individual subjects. The greater variability
      associated with stopwatch timing necessitates larger sample sizes. As defocus and
      light level were varied, reading acuity and standard letter acuity were highly
      correlated (r(2)  = 0.99), and reading acuity was slightly better. DISCUSSION: A
      computer-based IURead reading test provides a useful reading speed and reading
      acuity tool for clinical research involving multiple conditions and repeat
      testing of individual subjects. Ready to use IURead files for use with a
      computer, tablet or cell phone can be downloaded from our lab website
      (https://www.opt.indiana.edu/Bradley/Downloads.aspx).

PMID- 26303447
TI  - Development and validation of a new Chinese reading chart for children.
AB  - PURPOSE: This study aimed to develop and validate a new Chinese reading chart for
      children. The characteristics of reading profiles among Hong Kong children were
      also investigated. METHODS: A new reading chart was developed using the design
      principles of the MNREAD chart. Children (N = 169) aged seven to 11 years with
      normal vision and no developmental or reading difficulties were recruited from
      four local Hong Kong primary schools located in four different districts. Reading
      performance was measured using three versions of the new Chinese reading chart
      for children as well as six short passages. Repeated reading measures were
      conducted for 79 participants 4-8 weeks later. A linear mixed-model analysis was
      performed for the reading measures to identify the contribution of each source of
      variation (individual participant, among-charts within-session and between
      sessions, and error) to the total variance. RESULTS: Three reading parameters
      were derived from the Chinese reading chart for children - maximum reading speed
      (MRS), critical print size (CPS) and reading acuity (RA). Results from the linear
      mixed-model and Bland and Altman analyses revealed that all three versions of the
      chart were reproducible, with little variability among-charts and between
      sessions (p < 0.001). The coefficient of repeatability for the MRS, CPS and RA
      was 0.08 logWPM, 0.16 logMAR and 0.14 logMAR respectively. The strong correlation
      between reading speed measured by the chart and ordinary children's reading
      passages confirmed the usefulness of the chart for assessing children's reading
      performance (Rc = 0.67, 95% CI of 0.60-0.73). CONCLUSIONS: We developed and
      validated a new Chinese reading chart for children for quantifying reading
      performance in Chinese children with normal reading ability. This standardised
      clinical test can be reliably used to measure the MRS, CPS and RA in Chinese
      speaking children. Further research is needed to evaluate the validity of this
      chart for assessing reading performance in Chinese children with reading
      difficulties, dyslexia or low vision.

PMID- 26303448
TI  - Hazard detection with a monocular bioptic telescope.
AB  - PURPOSE: The safety of bioptic telescopes for driving remains controversial. The
      ring scotoma, an area to the telescope eye due to the telescope magnification,
      has been the main cause of concern. This study evaluates whether bioptic users
      can use the fellow eye to detect in hazards driving videos that fall in the ring
      scotoma area. METHODS: Twelve visually impaired bioptic users watched a series of
      driving hazard perception training videos and responded as soon as they detected
      a hazard while reading aloud letters presented on the screen. The letters were
      placed such that when reading them through the telescope the hazard fell in the
      ring scotoma area. Four conditions were tested: no bioptic and no reading,
      reading without bioptic, reading with a bioptic that did not occlude the fellow
      eye (non-occluding bioptic), and reading with a bioptic that partially-occluded
      the fellow eye. Eight normally sighted subjects performed the same task with the
      partially occluding bioptic detecting lateral hazards (blocked by the device
      scotoma) and vertical hazards (outside the scotoma) to further determine the
      cause-and-effect relationship between hazard detection and the fellow eye.
      RESULTS: There were significant differences in performance between conditions:
      83% of hazards were detected with no reading task, dropping to 67% in the reading
      task with no bioptic, to 50% while reading with the non-occluding bioptic, and
      34% while reading with the partially occluding bioptic. For normally sighted,
      detection of vertical hazards (53%) was significantly higher than lateral hazards
      (38%) with the partially occluding bioptic. CONCLUSIONS: Detection of driving
      hazards is impaired by the addition of a secondary reading like task. Detection
      is further impaired when reading through a monocular telescope. The effect of the
      partially-occluding bioptic supports the role of the non-occluded fellow eye in
      compensating for the ring scotoma.

PMID- 26303449
TI  - Retinal vessel oxygen saturation and vessel diameter in high myopia.
AB  - PURPOSE: To investigate changes in retinal vessel oxygen saturation and diameter
      in high myopia. METHODS: Relative oxygen saturation was measured in the retinal
      blood vessels of 54 participants with high myopia and compared to a control group
      of 54 individuals with emmetropia with the Oxymap T1 retinal oximeter. The
      participants with high myopia were further divided into two groups according to
      the grade of myopic retinopathy: Group A (grade < M2 ) and Group B (grade >= M2
      ). One-way anova was used to analyse the mean saturation and diameter of retinal
      arterioles and venules and the mean difference in arterio-venous saturation among
      the four groups. Further analysis of multiple comparisons was performed with the
      Bonferroni test. Linear regression was used to analyse the correlation of ocular
      perfusion pressure or best corrected visual acuity with other variables. RESULTS:
      For all of the high myopia patients, retinal arteriole saturation (92.3 +/- 5.6%)
      and the difference in arterio-venous saturation (30.8 +/- 5.0%) were
      significantly lower than in normal individuals (96.0 +/- 5.8%, 35.4 +/- 6.2%; p =
      0.006, p < 0.001, respectively). In Group A, only the difference in arterio
      venous saturation (31.0 +/- 4.7%) was significantly lower than in the control
      group (p = 0.011). In Group B, retinal arteriole saturation (92.2 +/- 5.3%) and
      the difference in arterio-venous saturation (30.7 +/- 5.3%) were also lower than
      the control group (p = 0.02, p = 0.001, respectively). Both retinal arteriole
      diameter and retinal venule diameter were narrower than in participants with high
      myopia than the control group (p < 0.001). No statistically significant
      correlations were found between ocular perfusion pressure or best corrected
      visual acuity with any other variables. CONCLUSIONS: The study demonstrated
      decreased retinal arteriole saturation and decreased difference in arterio-venous
      saturation as well as narrowing retinal vessel diameter in highly myopic eyes.
      Further studies are needed to determine if such changes play a role in the
      development of high myopia and its complications or occur as a consequence of
      tissue remodelling during axial elongation.

PMID- 26303450
TI  - Association of refractive error with optic nerve hypoplasia.
AB  - PURPOSE: To evaluate the association of refractive error with optic nerve
      hypoplasia (ONH). METHODS: A total of 30 ONH subjects were recruited and
      underwent comprehensive eye exams. Refractive error data from this group was
      compared to data from a group of 3232 non-ONH subjects from the same facility.
      Spherical equivalent was calculated to assess refractive error. Multiple logistic
      regression was used to evaluate the relationship between ONH and refractive error
      while controlling for age, race, and gender. RESULTS: The prevalence of hyperopia
      (>=+1.00 D), myopia (<-0.75 D), and anisometropia (>=1.00 D) was higher in ONH
      subjects than in controls. ONH subjects were 9.1 times more likely to be
      hyperopic than emmetropic (OR = 9.1, 95% CI = 2.9-28.4, p < 0.001) and 3.8 times
      more likely to be myopic than emmetropic (OR = 3.8, 95% CI = 1.2-11.5, p = 0.02).
      Unilateral ONH subjects were 10.0 times more likely to have anisometropia than
      controls (OR = 10.0, 95% CI = 3.9-25.6, p < 0.0001). Bilateral ONH subjects were
      3.8 times more likely to have anisometropia than controls (OR = 3.8, 95% CI = 1.1
      12.7, p = 0.03). CONCLUSIONS: Optic nerve hypoplasia subjects were more likely
      than control subjects to exhibit significant refractive errors, particularly
      hyperopia. Anisometropia tended to be more likely to occur in subjects with
      unilateral ONH than in bilateral ONH. Based on our findings, we recommend that
      clinicians perform a comprehensive eye examination on all patients with ONH and
      prescribe for existing refractive error when visual acuity or general visual
      function can realistically be improved.

PMID- 26303451
TI  - Effect of varying CRT refresh rate on the measurement of temporal summation.
AB  - PURPOSE: To quantify the effect of cathode-tube-ray (CRT) monitor refresh rate on
      the measurement of the upper limit of complete temporal summation (critical
      duration) in the peripheral visual field of healthy observers. METHODS: Contrast
      thresholds were measured for seven achromatic spot stimuli (diameter 0.48 degrees
      ) of varying duration (nominal values: 10-200 ms) at an eccentricity of 8.8
      degrees  along the 45 degrees , 135 degrees , 225 degrees  and 315 degrees 
      meridians of the visual field in three healthy, psychophysically experienced
      observers. Stimuli were presented on a CRT display with a refresh rate of 60 and
      160 Hz. Contrast thresholds were expressed as contrast energy with stimulus
      durations being estimated using (1) the sum-of-frames (SOF) method and (2)
      Bridgeman's method incorporating measurements of phosphor persistence. Estimates
      of the critical duration were produced using iterative two-phase regression
      analysis. RESULTS: With stimulus duration expressed as SOF equivalent the
      critical duration was, on average, 10.6 ms longer with a refresh rate of 60 Hz
      (mean 45.7 ms, S.D. 10.1 ms) relative to 160 Hz (35.1 ms, S.D. 7.6 ms). When the
      Bridgeman method was used, minimal differences (1.8 ms) in critical duration
      values between the two refresh rates (60 Hz: 33.0 ms, S.D. 9.4 ms; 160 Hz: 31.2
      ms, S.D. 7.0 ms) were observed. Identical trends were observed in all three
      subjects. CONCLUSIONS: Psychophysical measurements of temporal summation are
      independent of variations in CRT refresh rate when the Bridgeman method,
      incorporating measured values of phosphor persistence, is used to estimate
      stimulus duration. This has significant implications for the specification of
      stimulus duration in psychophysical studies of vision employing conventional
      display monitors.

PMID- 26303452
TI  - What proportion of sight loss is preventable? The need for a confidential enquiry
      for the eye care pathway.

PMID- 26303453
TI  - A clinical trial of the effect of sexual health education on the quality of life
      of married Muslim women in Iran.
AB  - BACKGROUND: Marital satisfaction is one of the key factors affecting women's
      holistic health. AIM: The present study was conducted to evaluate the effect of
      sexual health education on the quality of life in married women. METHODS: The
      present controlled clinical trial was conducted with a pretest-posttest design on
      a study population of 60 women (aged 20-45) admitted to select health centres
      affiliated to Tehran University of Medical Sciences. Samples were selected
      through convenience sampling and randomly allocated to an intervention group
      (n=30) and a control group (n=30). The data collection tool was the WHOQOL
      completed by participants first in the pretest and then in the follow-up posttest
      (after 2 months). The intervention group received sexual health education, while
      no interventions were provided to the control group. Data were analysed in SPSS
      16 using the paired t-test and the independent t-test. FINDINGS: Participants
      were matched in the two groups in terms of demographic variables such as age,
      occupation, age at marriage, duration of marriage, residential status and income
      level. At the baseline, no significant differences were observed between the
      intervention group (77.35+/-9.36) and the control group (75.64+/-8.32) in terms
      of the quality of life score (P=0.26). After the intervention, the quality of
      life score was 94.3+/-6.54 in the intervention group and 74.2+/-7.33 in the
      control group, making for a significant difference (P<0.01). CONCLUSION: Based on
      the findings, sexual health education can help women improve their sexual health
      through promoting sexual and marital satisfaction and consequently improve their
      quality of life.

PMID- 26303454
TI  - Clinical Management of Type 2 Diabetes Mellitus after Bariatric Surgery.
AB  - Bariatric surgery has emerged as an effective treatment for type 2 diabetes in
      the setting of obesity, with recent clinical trials demonstrating biochemical
      remission (i.e., euglycemia) in up to 40 % of subjects at 3 years post-surgery.
      Conversely, these trials also highlight that a significant proportion of
      individuals undergoing bariatric surgery experience residual diabetes (i.e., they
      do not achieve remission or experience diabetes recurrence). The management of
      residual diabetes following surgery requires personalized attention, yet limited
      evidence exists on which to base clinical decisions. Hence, we aim to review the
      evidence that does exist and propose clinical management strategies in patients
      with persistent hyperglycemia following bariatric surgery.

PMID- 26303455
TI  - Metabolic Surgery in Type 2 Diabetes: Roux-en-Y Gastric Bypass or Sleeve
      Gastrectomy as Procedure of Choice?
AB  - In recent years, a marked increase in the relative use of sleeve gastrectomy (SG)
      has occurred. However, long-term head-to-head comparison of the impact of this
      bariatric surgery (BS) procedure with the still considered "gold standard" Roux
      en-Y gastric bypass (GBP) in subjects with type 2 diabetes mellitus (T2DM) is
      surprisingly low. The aim of this review manuscript is to appraise current
      evidence on the potential of GBP and SG as long-term therapeutic tool for
      subjects with T2DM. In our opinion, unfortunately, review of current literature
      does not allow to properly answer which of the two surgeries would be better as
      procedure of choice for subjects with T2DM. Arguably, the apparent superiority of
      GBP over SG could be overcome by the addition of a malabsortive component to SG
      in a staged approach restricted to those failing to achieve the desired metabolic
      outcomes. Nonetheless, whether this serves as basis for the election of SG as
      primary strategy for those with T2DM is questionable.

PMID- 26303456
TI  - Activation of unfolded protein response pathway during infectious salmon anemia
      virus (ISAV) infection in vitro an in vivo.
AB  - Infectious salmon anemia virus (ISAV) is a salmon pathogen causing serious
      outbreaks in fish farms world-wide. There is currently no effective commercially
      available vaccine and there is a need for better understanding of host pathogen
      interactions with this virus. Various strains can cause both acute and persistent
      infections and therefore establish a balance with the host immune responses. We
      have studied host responses to this infection by analyzing the main branches of
      the unfolded protein response (UPR) in salmon cells in vitro and in tissues from
      infected fish to gain a better understanding of virus-host interactions. ISAV
      induce the main symptoms and signaling pathways of UPR (ATF6, PERK and IRE1)
      without inducing translational attenuation. This may be due to concomitant
      induction of an important negative feedback loop via the phosphatase regulator
      GADD34. The host cells can therefore respond with translation of cytokine and
      antiviral proteins to curb or control infection. 

PMID- 26303457
TI  - Angiomyolipoma with epithelial cysts: Add one to the differential of cystic renal
      lesions.

PMID- 26303458
TI  - Lithium Chloride Modulates Adipogenesis and Osteogenesis of Human Bone Marrow
      Derived Mesenchymal Stem Cells.
AB  - BACKGROUND/AIMS: Lithium chloride (LiCl) has long been used as a psychiatric
      medication; however, its role in the differentiation of bone marrow-derived
      mesenchymal stem cells (BMSCs) remains largely unknown. The aim of this study is
      to explore the effect of LiCl on the differentiation of BMSCs. METHODS: The roles
      of LiCl in osteogenic and adipogenic processes were observed using alizarin red
      staining and oil red O staining, respectively. The effects of LiCl on the Wnt and
      Hedgehog (Hh) pathways were investigated. RESULTS: Our data showed that LiCl
      effectively promoted osteogenesis and inhibited adipogenesis by simultaneously
      affecting the Wnt and Hh pathways. CONCLUSION: These results suggest that LiCl
      influences the differentiation of BMSCs directly through the Wnt and Hh pathways
      and thus may be a candidate drug for the treatment of osteoporosis.

PMID- 26303459
TI  - Effect of schistosomiasis on CX3CR1-expressing mononuclear phagocytes in the
      ileum and mesenteric lymph nodes of the mouse.
AB  - BACKGROUND: Intestinal dendritic cells (DCs) maintain immune homeostasis, only
      initiating an active immune response against invading pathogens. However, little
      information is available on the reaction of mononuclear phagocytes (MNP) to
      intestinal trematode infection, a reaction equally important in helminth-based
      therapies. The CD11c(+)  CX3CR1(+)  F4/80(-) DCs in the ileal lamina propria (LP)
      of the mouse were proven to migrate to the mesenteric lymph nodes (MLNs). We
      analyzed all MNP subsets present in the mouse LP and MLNs, under steady-state
      conditions and during acute Schistosoma mansoni-induced inflammation.
      Furthermore, we studied the uptake of schistosomal antigens by MNP in vivo in the
      LP and MLNs. METHODS: Using a combination of immunohistochemistry and
      multiparametric flow cytometry, we investigated distributional changes of the MNP
      during acute intestinal schistosomiasis. Next, S. mansoni-derived products, i.e.,
      S. mansoni soluble worm proteins (SmSWP) and S. mansoni soluble egg antigens
      (SmSEA) were intraperitoneally injected into CX3CR1(+/) (GFP) C57BL/6 mice and
      antigen uptake was analyzed using confocal microscopy. KEY RESULTS: The CD11c(+) 
      CX3CR1(+)  F4/80(-) DCs significantly increased during intestinal schistosomiasis
      in the LP and MLNs. Only CX3CR1-expressing DC and MF subsets, but not other LP
      DCs, are involved in both SmSWP and SmSEA antigen uptake and processing.
      CONCLUSIONS & INFERENCES: The significant upregulation of CD11c(+)  CX3CR1(+) 
      F4/80(-) DCs during intestinal schistosomiasis and the restriction of
      phagocytosis of parasitic antigens to CX3CR1-expresssing MNP indicate a crucial
      role for this immune cell niche in response to trematodiasis. These findings add
      insight into the functional specialization of LP immune cells and add to the
      understanding of cellular mechanisms behind helminth-based therapies.

PMID- 26303460
TI  - Serum screening in first trimester to predict pre-eclampsia, small for
      gestational age and preterm delivery: systematic review and meta-analysis.
AB  - BACKGROUND: Early assessment before the establishment of placental dysfunction
      has the potential to improve treatment and prognosis for clinical practice.The
      objective of the study is to investigate the accuracy of serum biochemical
      markers(Pregnancy- Associated Plasma Protein-A (PAPP-A), human Chorionic
      Gonadotropin (hCG), Placental Growth Factor (PlGF), Placental Protein 13 (PP13)
      used in first trimester serum screening in predicting preelampsia, small for
      gestational age (SGA) and preterm delivery. METHODS: The data sources included
      Medline, Embase, Cochrane library, Medion, hand searching of relevant journals,
      reference list checking of included articles and contact with experts. Two
      reviewers independently selected the articles. Two authors independently
      extracted data on study characteristics, quality and results. RESULTS: The
      results showed low predictive accuracy overall. For preeclampsia, the best
      predictor was PlGF; LR + 4.01 (3.74, 4.28), LR-(0.67, 0.64, 0.69). The predictive
      value of serum markers for early preeclampsia was better than that of late
      preeclampsia. For SGA the best predictor was PP13; LR+ 3.70 (3.39, 4.03), LR-
      0.70 (0.67, 0.73). For preterm delivery, the best predictor was PP13; LR+ 4.16
      (2.72, 5.61), LR- 0.56 (0.45, 0.67). CONCLUSION: First trimester screening
      analytes have low predictive accuracy for pre-eclampsia, small for gestational
      age and preterm delivery. However, the predict value of first trimester analytes
      is not worse than that of the second trimester markers.

PMID- 26303461
TI  - Epigenetic Regulation of Carotid Body Oxygen Sensing: Clinical Implications.
AB  - Recurrent apnea with intermittent hypoxia (IH) is a major clinical problem in
      infants born preterm. Recent epidemiological studies showed that adults who were
      born preterm exhibit increased incidence of sleep-disordered breathing and
      hypertension. Thus, apnea of prematurity predisposes individuals to autonomic
      dysfunction in adulthood. Experimental studies showed that adult rats exposed to
      IH as neonates exhibit augmented carotid body and adrenal chromaffin cells (AMC)
      response to hypoxia and irregular breathing with apneas and hypertension. The
      enhanced hypoxic sensitivity of the carotid body and AMC in adult rats exposed to
      neonatal IH was associated with increased oxidative stress, decreased expression
      of genes encoding anti-oxidant enzymes, and increased expression of pro-oxidant
      enzymes. Epigenetic mechanisms including DNA methylation leads to long-term
      changes in gene expression. The decreased expression of the Sod2 gene, which
      encodes the anti-oxidant enzyme, superoxide dismutase 2, was associated with DNA
      hypermethylation of a single CpG dinucleotide close to the transcription start
      site. Treating neonatal rats with decitabine, an inhibitor of DNA methylation,
      during IH exposure prevented the oxidative stress, enhanced hypoxic sensitivity,
      and autonomic dysfunction in adult rats. These findings suggest that epigenetic
      mechanisms, especially DNA methylation contributes to neonatal programming of
      hypoxic sensitivity and the ensuing autonomic dysfunction in adulthood. 

PMID- 26303462
TI  - Experimental Observations on the Biological Significance of Hydrogen Sulfide in
      Carotid Body Chemoreception.
AB  - The cascade of transduction of hypoxia and hypercapnia, the natural stimuli to
      chemoreceptor cells, is incompletely understood. A particular gap in that
      knowledge is the role played by second messengers, or in a most ample term, of
      modulators. A recently described modulator of chemoreceptor cell responses is the
      gaseous transmitter hydrogen sulfide, which has been proposed as a specific
      activator of the hypoxic responses in the carotid body, both at the level of the
      chemoreceptor cell response or at the level of the global output of the organ.
      Since sulfide behaves in this regard as cAMP, we explored the possibility that
      sulfide effects were mediated by the more classical messenger. Data indicate that
      exogenous and endogenous sulfide inhibits adenyl cyclase finding additionally
      that inhibition of adenylyl cyclase does not modify chemoreceptor cell responses
      elicited by sulfide. We have also observed that transient receptor potential
      cation channels A1 (TRPA1) are not regulated by sulfide in chemoreceptor cells. 

PMID- 26303463
TI  - The CamKKbeta Inhibitor STO609 Causes Artefacts in Calcium Imaging and
      Selectively Inhibits BKCa in Mouse Carotid Body Type I Cells.
AB  - It has previously been reported that AMP-activated protein kinase (AMPK) may be
      critical for hypoxic chemotransduction in carotid body type I cells. This study
      sought to determine the importance of the regulatory upstream kinase of AMPK,
      CamKKbeta, in the acute response to hypoxia in isolated mouse type I
      cells.Initial data indicated several previously unreported artefacts associated
      with using the CamKKbeta inhibitor STO609 and Ca(2+) imaging techniques. Most
      importantly Fura-2 and X-Rhod1 imaging revealed that STO609 quenched emission
      fluorescence even in the absence of intracellular Ca(2+) ([Ca(2+)](I)).
      Furthermore, STO609 (100 MUM) rapidly inhibited outward macroscopic currents and
      this inhibition was abolished in the presence of the selective BK(Ca) inhibitor
      paxilline.Taken together these data suggest that ST0609 should be used with
      caution during Ca(2+) imaging studies as it can directly interact with Ca(2+)
      binding dyes. The rapid inhibitory effect of STO609 on BK(Ca) was unexpected as
      the majority of studies using this compound required an incubation of
      approximately 10 min to inhibit the kinase. Furthermore, as AMPK activation
      inhibits BK(Ca), inhibiting AMPK's upstream kinases would, if anything, be
      predicted to have the opposite effect on BK(Ca). Future work will determine if
      the inhibition of BK(Ca) is via CamKKbeta or via an off target action of STO609
      on the channel itself.

PMID- 26303464
TI  - Tissue Dynamics of the Carotid Body Under Chronic Hypoxia: A Computational Study.
AB  - The carotid body (CB) increases in volume in response to chronic continuous
      hypoxia and the mechanisms underlying this adaptive response are not fully
      elucidated. It has been proposed that chronic hypoxia could lead to the
      generation of a sub-population of type II cells representing precursors, which,
      in turn, can give rise to mature type I cells. To test whether this process could
      explain not only the observed changes in cell number, but also the micro
      anatomical pattern of tissue rearrangement, a mathematical modeling approach was
      devised to simulate the hypothetical sequence of cellular events occurring within
      the CB during chronic hypoxia. The modeling strategy involved two steps. In a
      first step a "population level" modeling approach was followed, in order to
      estimate, by comparing the model results with the available experimental data,
      "macroscopic" features of the cell system, such as cell population expansion
      rates and differentiation rates. In the second step, these results represented
      key parameters to build a "cell-centered" model simulating the self-organization
      of a system of CB cells under a chronic hypoxic stimulus and including cell
      adhesion, cytoskeletal rearrangement, cell proliferation, differentiation, and
      apoptosis. The cell patterns generated by the model showed consistency (from both
      a qualitative and quantitative point of view) with the observations performed on
      real tissue samples obtained from rats exposed to 16 days hypoxia, indicating
      that the hypothesized sequence of cellular events was adequate to explain not
      only changes in cell number, but also the tissue architecture acquired by CB
      following a chronic hypoxic stimulus. 

PMID- 26303465
TI  - Paracrine Signaling in Glial-Like Type II Cells of the Rat Carotid Body.
AB  - The carotid body (CB) chemosensory complex uses ATP as a key excitatory
      neurotransmitter that is the main contributor to the sensory discharge during
      acute hypoxia. The complex includes receptor type I cells, which depolarize and
      release various neurochemicals including ATP during hypoxia, and contiguous glial
      like type II cells which express purinergic P2Y2 receptors (P2Y2R). We previously
      showed that activation of P2Y2R on rat type II cells led to the opening of
      pannexin-1 (Panx-1) channels, which acted as conduits for the further release of
      ATP. More recently, we considered the possibility that other CB neuromodulators
      may have a similar paracrine role, leading to the activation of type II cells.
      Here, we examine the evidence that angiotensin II (ANG II), endothelin- (ET-1),
      and muscarinic agonists (e.g. acetylcholine, ACh) may activate intracellular
      Ca(2+) signals in type II cells and, in the case of ANG II and ACh, Panx-1
      currents as well. Using ratiometric Ca(2+) imaging, we found that a substantial
      population of type II cells responded to 100 nM ANG II with a robust rise in
      intracellular Ca(2+) and activation of Panx-1 current. Both effects of ANG II
      were mediated via AT(1) receptors (AT(1)Rs) and current activation could be
      inhibited by the Panx-1 channel blocker, carbenoxolone (CBX; 5 MUM).
      Additionally, low concentrations of ET-1 (1 nM) evoked robust intracellular
      Ca(2+) responses in subpopulations of type II cells. The mAChR agonist muscarine
      (10 MUM) also induced a rise in intracellular Ca(2+) in some type II cells, and
      preliminary perforated-patch, whole-cell recordings revealed that ACh (10 MUM)
      may activate Panx-1-like currents. These data suggest that paracrine activation
      of type II cells by endogenous neuromodulators may be a common feature of signal
      processing in the rat CB.

PMID- 26303466
TI  - Selective mu and kappa Opioid Agonists Inhibit Voltage-Gated Ca2+ Entry in
      Isolated Neonatal Rat Carotid Body Type I Cells.
AB  - It is known that opioids inhibit the hypoxic ventilatory response in part via an
      action at the carotid body, but little is known about the cellular mechanisms
      that underpin this. This study's objectives were to examine which opioid
      receptors are located on the oxygen-sensing carotid body type I cells from the
      rat and determine the mechanism by which opioids might inhibit cellular
      excitability.Immunocytochemistry revealed the presence of MU and kappa opioid
      receptors on type I cells. The MU-selective agonist DAMGO (10 MUM) and the kappa
      selective agonist U50-488 (10 MUM) inhibited high K(+) induced rises in
      intracellular Ca(2+) compared with controls. After 3 h incubation (37  degrees C)
      with pertussis toxin (150 ng ml(-1)), DAMGO (10 MUM) and U50-488 (10 MUM) had no
      significant effect on the Ca(2+) response to high K(+).These results indicate
      that opioids acting at MU and kappa receptors inhibit voltage-gated Ca(2+) influx
      in rat carotid body type I cells via G(i)-coupled mechanisms. This mechanism may
      contribute to opioid's inhibitory actions in the carotid body.

PMID- 26303467
TI  - Measurement of ROS Levels and Membrane Potential Dynamics in the Intact Carotid
      Body Ex Vivo.
AB  - Reactive oxygen species (ROS) generated by the NADPH oxidase have been proposed
      to play an important role in the carotid body (CB) oxygen sensing process (Cross
      et al. 1990). Up to now it remains unclear whether hypoxia causes an increase or
      decrease of CB ROS levels. We transfected CBs with the ROS sensitive HSP-FRET
      construct and subsequently measured the intracellular redox state by means of
      Forster resonance energy transfer (FRET) microscopy. In a previous study we found
      both increasing and decreasing ROS levels under hypoxic conditions. The
      transition from decreasing to increasing ROS levels coincided with the change of
      the caging system from ambient environment caging (AEC) to individually
      ventilated caging (IVC) (Bernardini A, Brockmeier U, Metzen E, Berchner
      Pfannschmidt U, Harde E, Acker-Palmer A, Papkovsky D, Acker H, Fandrey J, Type I
      cell ROS kinetics under hypoxia in the intact mouse carotid body ex vivo: a FRET
      based study. Am J Physiol Cell Physiol. doi: 10.1152/ajpcell.00370.2013 , 2014).
      In this work we analyze hypoxia induced ROS reaction of animals from an IVC
      system that had been exposed to AEC conditions for 5 days. The results further
      support the hypothesis of an important impact of the caging system on CB ROS
      reaction. 

PMID- 26303468
TI  - Acutely Administered Leptin Increases [Ca2+] i and BK Ca Currents But Does Not
      Alter Chemosensory Behavior in Rat Carotid Body Type I Cells.
AB  - Obesity related pathologies are the health care crisis of our generation. The fat
      cell derived adipokine leptin has been shown to be a central stimulant of
      respiration. Very high levels of leptin, however, are associated with the
      depressed ventilatory phenotype observed in obesity hypoventilation syndrome.
      Leptin receptors have been identified on carotid body type I cells but how their
      activation might influence the physiology of these cells is not known.The acute
      application of leptin evoked calcium signaling responses in isolated type I
      cells. Cells increased their Fura 2 ratio by 0.074 +/- 0.010 ratio units (n = 39,
      P < 0.001). Leptin also increased the peak membrane currents in 6 of 9 cells
      increasing the peak macroscopic currents at +10 mV by 61 +/- 14 % (p < 0.02).
      Leptin administered in the presence of the selective BK(Ca) channel inhibitor
      Paxilline (0.5 MUM) failed to increase membrane currents (n = 5). Interestingly,
      leptin did not significantly alter the resting membrane potential of isolated
      type I cells (n = 9) and anoxic/acidic depolarizations were unaffected by leptin
      (n = 7, n = 6).These data suggest that leptin receptors are functional in type I
      cells but that their acute activation does not alter chemosensory properties.
      Future studies will use chronic models of leptin dysregulation.

PMID- 26303469
TI  - Functional Properties of Mitochondria in the Type-1 Cell and Their Role in Oxygen
      Sensing.
AB  - The identity of the oxygen sensor in arterial chemoreceptors has been the subject
      of much speculation. One of the oldest hypotheses is that oxygen is sensed
      through oxidative phosphorylation. There is a wealth of data demonstrating that
      arterial chemoreceptors are excited by inhibitors of oxidative phosphorylation.
      These compounds mimic the effects of hypoxia inhibiting TASK1/3 potassium
      channels causing membrane depolarisation calcium influx and neurosecretion. The
      TASK channels of Type-I cells are also sensitive to cytosolic MgATP. The
      existence of a metabolic signalling pathway in Type-1 cells is thus established;
      the contentious issue is whether this pathway is also used for acute oxygen
      sensing. The main criticism is that because cytochrome oxidase has a high
      affinity for oxygen (P50 ~ 0.2 mmHg) mitochondrial metabolism should be
      insensitive to physiological hypoxia. This argument is however predicated on the
      assumption that chemoreceptor mitochondria are analogous to those of other
      tissues. We have however obtained new evidence to support the hypothesis that
      type-1 cell mitochondria are not like those of other cells in that they have an
      unusually low affinity for oxygen (Mills E, Jobsis FF, J Neurophysiol 35(4):405
      428, 1972; Duchen MR, Biscoe TJ, J Physiol 450:13-31, 1992a). Our data confirm
      that mitochondrial membrane potential, NADH, electron transport and cytochrome
      oxidase activity in the Type-1 cell are all highly sensitive to hypoxia. These
      observations not only provide exceptionally strong support for the metabolic
      hypothesis but also reveal an unknown side of mitochondrial behaviour. 

PMID- 26303470
TI  - Potentiation of Hypoxic Pulmonary Vasoconstriction by Hydrogen Sulfide Precursors
      3-Mercaptopyruvate and D-Cysteine Is Blocked by the Cystathionine gamma Lyase
      Inhibitor Propargylglycine.
AB  - Although the gasotransmitter hydrogen sulfide (H(2)S) generally dilates systemic
      arteries in mammals, it causes constriction of pulmonary arteries. In isolated
      rat pulmonary arteries, we have shown that the H(2)S precursor cysteine enhances
      both hypoxic pulmonary vasoconstriction and tension development caused by the
      agonist prostaglandin F(2alpha) under normoxic conditions. These effects were
      blocked by propargylglycine (PAG), a blocker of the enzyme cystathionine gamma
      lyase which metabolises cysteine to sulfide. In the present study, we evaluated
      whether 3-mercaptopyruvate (3-MP), a sulfide precursor which is thought to give
      rise to sulfide when it is metabolised by the enzyme mercaptopyruvate
      sulfurtransferase, also enhanced contraction. Application of 3-MP prior to
      hypoxic challenge caused a marked enhancement of HPV which was completely blocked
      by both L- and D,L-PAG (both 1 mM). Cumulative application of 3-1,000 MUM 3-MP
      during an ongoing contraction to PGF(2alpha) under normoxic conditions also
      caused a marked increase in tension. Application of D-cysteine (1 mM) also
      enhanced HPV, and this effect was prevented by both the D-amino acid oxidase
      inhibitor sodium benzoate (500 MUM) and 1 mM L-PAG.

PMID- 26303471
TI  - Modulation of the LKB1-AMPK Signalling Pathway Underpins Hypoxic Pulmonary
      Vasoconstriction and Pulmonary Hypertension.
AB  - Perhaps the defining characteristic of pulmonary arteries is the process of
      hypoxic pulmonary vasoconstriction (HPV) which, under physiological conditions,
      supports ventilation-perfusion matching in the lung by diverting blood flow away
      from oxygen deprived areas of the lung to oxygen rich regions. However, when
      alveolar hypoxia is more widespread, either at altitude or with disease (e.g.,
      cystic fibrosis), HPV may lead to hypoxic pulmonary hypertension. HPV is driven
      by the intrinsic response to hypoxia of pulmonary arterial smooth muscle and
      endothelial cells, which are acutely sensitive to relatively small changes in pO2
      and have evolved to monitor oxygen supply and thus address ventilation-perfusion
      mismatch. There is now a consensus that the inhibition by hypoxia of
      mitochondrial oxidative phosphorylation represents a key step towards the
      induction of HPV, but the precise nature of the signalling pathway(s) engaged
      thereafter remains open to debate. We will consider the role of the AMP-activated
      protein kinase (AMPK) and liver kinase B1 (LKB1), an upstream kinase through
      which AMPK is intimately coupled to changes in oxygen supply via mitochondrial
      metabolism. A growing body of evidence, from our laboratory and others, suggests
      that modulation of the LKB1-AMPK signalling pathway underpins both hypoxic
      pulmonary vasoconstriction and the development of pulmonary hypertension. 

PMID- 26303472
TI  - Organismal Responses to Hypoxemic Challenges.
AB  - As a counterpoint to the volumes of beautiful work exploring how the carotid
      bodies (CBs) sense and transduce stimuli into neural traffic, this study explored
      one organismal reflex response to such stimulation. We challenged the
      anesthetized, paralyzed, artificially ventilated cat with two forms of acute
      hypoxemia: 10 % O(2)/balance N(2) (hypoxic hypoxia [HH] and carbon monoxide
      hypoxia [COH]). HH stimulates both CBs and aortic bodies (ABs), whereas COH
      stimulates only the ABs. Our design was to stimulate both with HH (HHint), then
      to stimulate only the ABs with COH (COHint); then, after aortic depressor nerve
      transaction, only the CBs with HH (HHabr), and finally neither with COH (COHabr).
      We recorded whole animal responses from Group 1 cats (e.g., cardiac output,
      arterial blood pressure, pulmonary arterial pressure/and vascular resistance)
      before and after sectioning the aortic depressor nerves. From Group 2 cats
      (intact) and Group 3 cats (aortic body resected) we recorded the vascular
      resistance in several organs (e.g., brain, heart, spleen, stomach, pancreas,
      adrenal glands, eyes). The HHint challenge was the most effective at keeping
      perfusion pressures adequate to maintain homeostasis in the face of a systemic
      wide hypoxemia with locally mediated vasodilation. The spleen and pancreas,
      however, showed a vasoconstrictive response. The adrenals and eyes showed a CB
      mediated vasodilation. The ABs appeared to have a significant impact on the
      pulmonary vasculature as well as the stomach. Chemoreceptors via the sympathetic
      nervous system play the major role in this organism's response to hypoxemia.

PMID- 26303473
TI  - Effect of Lipopolysaccharide Exposure on Structure and Function of the Carotid
      Body in Newborn Rats.
AB  - Premature infants are vulnerable to infections and have unstable breathing (Di
      Fiore JM, Martin RJ, Gauda EB, Respir Physiol Neurobiol 189:213-222, 2013).
      Inflammation adversely modifies carotid body (CB) structure and chemosensitivity
      in adult animals. We determined the effect of inflammation on CB structure and
      function in newborn rat pups. Pups were given LPS (0.1 mg/kg; IP) or saline at
      postnatal day 2 (P2). At P9-10 (1 week after exposure) various studies were done
      including ventilation, carotid sinus nerve (CSN) activity and histology. Using
      whole body plethysmography, we found that LPS exposure attenuates the change in
      interbreath (IBI) interval in response to changes in oxygen tension 1 week after
      LPS exposure. The response of the CSN to hypoxia was attenuated and delayed in
      onset in LPS-treated animals as compared to controls. Histological sections of
      the CB were examined for inflammatory cells at P4 (n = 7) and P9-12 (n = 6).
      After LPS exposure, only mast cells were seen, often encircling the CB, and
      clustered within the CSN as it entered the CB. Mast cells per section (mean +/-
      SEM) were higher at P9-12 in LPS (7.4 +/- 1.5) vs saline (5.4 +/- 1.4) exposed
      animals (p = 0.04). Surprisingly, more mast cells were seen at 7-10 days vs 48 h
      after LPS exposure. In a newborn model of inflammation, breathing is altered
      which is associated with changes in structure and function of the carotid body.

PMID- 26303474
TI  - Hypoxic Ventilatory Reactivity in Experimental Diabetes.
AB  - Diabetes, apart from generalized neuropathy and microangiopathy, involves tissue
      hypoxia, which may drive chronic proinflammatory state. However, studies on the
      ventilatory control in diabetes are sparse and conflicting. In this study we
      examined the function and morphology of diabetic carotid bodies (CBs). Diabetes
      was evoked in Wistar rats with streptozotocin (70 mg/kg, i.p.). The acute hypoxic
      ventilatory responses (HVR) to 12 and 8 % O(2) were investigated in conscious
      untreated rats after 2 and 4 weeks in a plethysmographic chamber. CBs were
      dissected and subjected to morphologic investigations: (1) electron transmission
      microscopy for ultrastructure and (2) laser scanning confocal microscopy to
      visualize the microvascular bed in sections labeled with the lectin Griffonia
      simplicifolia-I (GSI), an endothelial cell marker, and fluorescein isothiocyanate
      (FITC). All findings were referenced to the normal healthy rats. We found that
      diabetes distinctly dampened the HVR. At the ultrastructural level, the diabetic
      CB displayed proliferation of connective tissue and neovascularization deranging
      the interglomal structure, and lengthening the O(2) diffusion path from
      capillaries to chemoreceptor cells. The chemoreceptor cells remained largely
      unchanged. The endothelial cell labeling confirmed the intensive angiopathy and
      the induction of microvessel growth. We conclude that diabetes hampers the
      chemical regulation of ventilation due to remodeling of CB parenchyma, which may
      facilitate chronic hypoxia and inflammation in the organ.

PMID- 26303475
TI  - Adenosine Receptor Blockade by Caffeine Inhibits Carotid Sinus Nerve Chemosensory
      Activity in Chronic Intermittent Hypoxic Animals.
AB  - Adenosine is a key excitatory neurotransmitter at the synapse between O(2)
      sensing chemoreceptor cells-carotid sinus nerve (CSN) endings in the carotid body
      (CB). Herein, we have investigated the significance of adenosine, through the
      blockade of its receptors with caffeine, on the CB hypoxic sensitization induced
      by chronic intermittent hypoxia (CIH) in the rat. CIH animals were obtained by
      submitting rats during 15 days from 8:00 to 16:00 to 10 %O(2) for 40 s and 20 %
      O(2) for 80 s (i.e., 30 episodes/h). Caffeine (1 mM) was tested in spontaneous
      and 5 %O(2) evoked-CSN chemosensory activity in normoxic and CIH animals. CIH
      decreased basal spontaneous activity but increased significantly CSN activity
      evoked by acute hypoxia. Caffeine did not modify basal spontaneous activity in
      normoxic rats, but decreased significantly by 47.83 % basal activity in CIH
      animals. In addition, acute application of caffeine decreased 49.31 % and 56.01 %
      the acute hypoxic response in normoxic and CIH animals, respectively. We
      demonstrate that adenosine contributes to fix CSN basal activity during CIH,
      being also involved in hypoxic CB chemotransduction. It is concluded that
      adenosine participates in CB sensitization during CIH.

PMID- 26303476
TI  - Neurotrophic Properties, Chemosensory Responses and Neurogenic Niche of the Human
      Carotid Body.
AB  - The carotid body (CB) is a polymodal chemoreceptor that triggers the
      hyperventilatory response to hypoxia necessary for the maintenance of O(2)
      homeostasis essential for the survival of organs such as the brain or heart.
      Glomus cells, the sensory elements in the CB, are also sensitive to hypercapnia,
      acidosis and, although less generally accepted, hypoglycemia. Current knowledge
      on CB function is mainly based on studies performed on lower mammals, but the
      information on the human CB is scant. Here we describe the structure,
      neurotrophic properties, and cellular responses to hypoxia and hypoglycemia of
      CBs dissected from human cadavers. The adult CB parenchyma contains clusters of
      chemosensitive glomus (type I) and sustentacular (type II) cells as well as
      nestin-positive progenitor cells. This organ also expresses high levels of the
      dopaminotrophic glial cell line-derived neurotrophic factor (GDNF). GDNF
      production and the number of progenitor and glomus cells were preserved in the
      CBs of human subjects of advanced age. As reported for other mammalian species,
      glomus cells responded to hypoxia by external Ca(2+)-dependent increase of
      cytosolic [Ca(2+)] and quantal catecholamine release. Human glomus cells are also
      responsive to hypoglycemia and together the two stimuli, hypoxia and
      hypoglycemia, can potentiate each other's effects. The chemo-sensory responses of
      glomus cells are also preserved at an advanced age. Interestingly, a neurogenic
      niche similar to that recently described in rodents is also preserved in the
      adult human CB. These new data on the cellular and molecular physiology of the CB
      pave the way for future pathophysiological studies involving this organ in
      humans.

PMID- 26303477
TI  - Is the Carotid Body a Metabolic Monitor?
AB  - The carotid body is a multi-modal sensor and it has been debated if it senses low
      glucose. We have hypothesized that the carotid body is modified by some metabolic
      factors other than glucose and contributes to whole body glucose metabolism. This
      study examined the roles of insulin, leptin and transient receptor potential
      (TRP) channels on carotid sinus nerve (CSN) chemoreceptor discharge. In agreement
      with other studies, CSN activity was not modified by low glucose. Insulin did not
      affect the CSN hypoxic response. Leptin significantly augmented the CSN response
      to hypoxia and nonspecific Trp channel blockers (SKF96365, 2-APB) reversed the
      effect of leptin. Gene expression analysis showed high expression of Trpm3, 6,
      and 7 channels in the carotid body and petrosal ganglion. The results suggest
      that the adult mouse carotid body does not sense glucose levels directly. The
      carotid body may contribute to neural control of glucose metabolism via leptin
      receptor-mediated TRP channel activation. 

PMID- 26303478
TI  - Lipopolysaccharide-Induced Ionized Hypocalcemia and Acute Kidney Injury in
      Carotid Chemo/Baro-Denervated Rats.
AB  - The acute kidney injury (AKI) observed during sepsis is due to an uncontrolled
      release of inflammatory mediators. Septic patients develop electrolytic
      disturbances and one of the most important is ionized hypocalcemia. AKI adversely
      affects the function of other organs and hypocalcemia is associated with
      cardiovascular and respiratory dysfunctions. Since carotid body chemoreceptors
      modulate the systemic inflammatory response during sepsis syndromes, we used
      pentobarbitone-anesthetized male Sprague-Dawley rats in control condition (SHAM
      surgery) and after bilateral carotid neurotomy (carotid chemo/baro-denervated,
      BCN). We evaluate serum creatinine (CRE), serum neutrophil gelatinase-associated
      lipocaline (NGAL), ionized calcium (iCa) and cardiac Troponin I (cTnI) 90 min
      after the IP administration of 15 mg/kg lipopolysaccharide (LPS) or saline. In
      the SHAM group, LPS failed to induce significant changes CRE, NGAL, or iCa, and
      increased cTnI. Conversely, in the BCN group LPS increased CRE and NGAL,
      decreased iCa, and enhanced the increase of cTnI. Our results suggest that
      carotid chemo/baro-receptors might contribute to the regulation of both renal
      function and calcemia during sepsis. In addition, results imply that the carotid
      chemo-baroreceptors serve as an immunosensory organ. 

PMID- 26303479
TI  - Role of the Carotid Body Chemoreflex in the Pathophysiology of Heart Failure: A
      Perspective from Animal Studies.
AB  - The treatment and management of chronic heart failure (CHF) remains an important
      focus for new and more effective clinical strategies. This important goal,
      however, is dependent upon advancing our understanding of the underlying
      pathophysiology. In CHF, sympathetic overactivity plays an important role in the
      development and progression of the cardiac and renal dysfunction and is often
      associated with breathing dysregulation, which in turn likely mediates or
      aggravates the autonomic imbalance. In this review we will summarize evidence
      that in CHF, the elevation in sympathetic activity and breathing instability that
      ultimately lead to cardiac and renal failure are driven, at least in part, by
      maladaptive activation of the carotid body (CB) chemoreflex. This maladaptive
      change derives from a tonic increase in CB afferent activity. We will focus our
      discussion on an understanding of mechanisms that alter CB afferent activity in
      CHF and its consequence on reflex control of autonomic, respiratory, renal, and
      cardiac function in animal models of CHF. We will also discuss the potential
      translational impact of targeting the CB in the treatment of CHF in humans, with
      relevance to other cardio-respiratory diseases. 

PMID- 26303480
TI  - A Short-Term Fasting in Neonates Induces Breathing Instability and Epigenetic
      Modification in the Carotid Body.
AB  - The respiratory control system is not fully developed in newborn, and data
      suggest that adequate nutrition is important for the development of the
      respiratory control system. Infants need to be fed every 2-4 h to maintain
      appropriate energy levels, but a skip of feeding can occur due to social
      economical reasons or mild sickness of infants. Here, we asked questions if a
      short-term fasting (1) alters carotid body (CB) chemoreceptor activity and
      integrated function of the respiratory control system; (2) causes epigenetic
      modification within the respiratory control system. Mouse pups (<P14) were fasted
      for 3-6 h. Breathing became irregular and slow. The number and duration of apnea
      increased. Ventilatory response to hypoxia was also depressed even after the pups
      were returned to own dams. These effects were more prominent when the pups were
      younger and fasting time was longer. The hypoxic response of the carotid sinus
      nerve activity appeared to be depressed after fasting. Moreover, fasting
      increased global 5mC and 5-hmC content in DNA isolated from the CB but not DNA in
      the superior cervical ganglion (SCG). Methylation specific PCR (MSPCR) revealed
      that fasting increased methylation of leptin and socs3 genes. The results suggest
      fasting inhibits CB activity leading to hypoventilation, and low glucose does not
      compensate the low CB activity. Epigenetic effect on CB function/activity may be
      related to the prolonged effect of fasting on ventilation. 

PMID- 26303481
TI  - Carotid Body Chemoreflex Mediates Intermittent Hypoxia-Induced Oxidative Stress
      in the Adrenal Medulla.
AB  - Intermittent hypoxia (IH) increases reactive oxygen species generation resulting
      in oxidative stress in the adrenal medulla (AM), a major end-organ of the
      sympathetic nervous system which facilitates catecholamine secretion by hypoxia.
      Here, we show that carotid body chemoreflex contributes to IH-induced oxidative
      stress in the AM. Carotid bodies were ablated by cryocoagulation of glomus cells,
      the putative O(2) sensing cells. Carotid body ablated (CBA) and control rats were
      exposed to IH and the redox state of the AM was assessed biochemically. We found
      that IH raised reactive oxygen species levels along with an increase in NADPH
      oxidase (Nox), a pro-oxidant enzyme and a decrease in superoxide dismutase-2
      (SOD2), an anti-oxidant enzyme. Further, IH increased hypoxia-inducible factor
      (HIF)-1alpha, whereas decreased HIF-2alpha, the transcriptional regulator of Nox
      and SOD-2, respectively. These IH-induced changes in the AM were absent in CBA
      rats. Moreover, IH increased splanchnic nerve activity and facilitated hypoxia
      evoked catecholamine efflux from the AM and CBA prevented these effects. These
      findings suggest that IH-induced oxidative stress and catecholamine efflux in the
      AM occurs via carotid body chemoreflex involving HIF alpha isoform mediated
      imbalance in pro-, and anti-oxidant enzymes.

PMID- 26303482
TI  - The Association Between Antihypertensive Medication and Blood Pressure Control in
      Patients with Obstructive Sleep Apnea.
AB  - Obstructive sleep apnea and hypertension are closely related diseases. The
      lowering effect of continuous positive airway pressure (CPAP) on blood pressure
      (BP) control is modest and concomitant antihypertensive therapy is still
      required. However, the best antihypertensive regimen for BP control in patients
      with OSA remains unknown. We aimed to investigate a hypothetical association
      between ongoing antihypertensive medication and BP control rates in patients with
      OSA. We conducted a prospective observational study in a cohort of 205 patients
      with OSA and hypertension who underwent a sleep study and 24-h ambulatory blood
      pressure monitoring (ABPM). Ongoing antihypertensive medication profile was
      recorded. Logistic regression models were used to investigate the association
      between antihypertensive regimen and BP control, before (n = 205) and, when
      applicable, after CPAP adaptation (n = 90). One hundred and fifty-five patients
      (155/205) were being treated with 31 different antihypertensive regimens. At
      baseline, the antihypertensive regimens and the number of antihypertensive drugs
      were not associated with BP control (p = 0.847; p = 0.991). After CPAP
      adaptation, a decrease in median night-time systolic and diastolic BP was
      observed (p = 0.001; p = 0.006). Nevertheless, the lack of association between
      antihypertensive regimens and the number of antihypertensive drugs and BP control
      remained (p = 0.864; p = 0.800). Our findings confirm that although CPAP improves
      nocturnal BP, this improvement is not sufficient to control blood pressure for 24
      h. This study shows, for the first time, that in patients with OSA, there is no
      association between BP control and both the antihypertensive regimen and the
      number of antihypertensive drugs. 

PMID- 26303483
TI  - An Overview on the Respiratory Stimulant Effects of Caffeine and Progesterone on
      Response to Hypoxia and Apnea Frequency in Developing Rats.
AB  - The respiratory stimulant caffeine is the most frequently used xanthine
      (theophylline or aminophylline) for the treatment of apnea in premature infants.
      It decreases but does not eliminate apnea. In most cases such decreases is
      insufficient to prevent the use of artificial ventilation. Progesterone is a
      respiratory stimulant in adult mammals including human, and it decreases sleep
      apnea in menopausal women. Whether progesterone as an adjunct to caffeine therapy
      could be effective in further reducing the frequency of apnea in premature
      infants is not known because its respiratory effect in newborns has not been well
      studied. Using rat pups at different postnatal ages, we first determined whether
      the respiratory stimulant effects of acute caffeine (10 mg/kg, i.p.) or
      progesterone (4 mg/kg i.p.) are age dependent. These studies showed that caffeine
      enhances the ventilatory response to hypoxia in 1 and 4 days-old rats while it
      decreases apnea frequency in 12-days-old. In contrast, progesterone enhances the
      ventilatory response to hypoxia in less than 7-days-old but decreases apnea in 1
      day-old rats. Preliminary experiments show that administration of progesterone (4
      mg/kg i.p.) to newborn rats that are chronically treated with caffeine (mimicking
      its clinical uses - 7.5 mg/kg once/day by gavage) enhances the respiratory
      stimulant effects of caffeine. Surprisingly, acute injection of progesterone
      enhances apnea frequency and reduces hypoxic ventilatory response in 12-day-old
      rats. 

PMID- 26303484
TI  - Hyperbaric Oxygen Therapy Improves Glucose Homeostasis in Type 2 Diabetes
      Patients: A Likely Involvement of the Carotid Bodies.
AB  - The carotid bodies (CBs) are peripheral chemoreceptors that respond to hypoxia
      increasing minute ventilation and activating the sympathetic nervous system.
      Besides its role in ventilation we recently described that CB regulate peripheral
      insulin sensitivity. Knowing that the CB is functionally blocked by hyperoxia and
      that hyperbaric oxygen therapy (HBOT) improves fasting blood glucose in diabetes
      patients, we have investigated the effect of HBOT on glucose tolerance in type 2
      diabetes patients. Volunteers with indication for HBOT were recruited at the
      Subaquatic and Hyperbaric Medicine Center of Portuguese Navy and divided into two
      groups: type 2 diabetes patients and controls. Groups were submitted to 20
      sessions of HBOT. OGTT were done before the first and after the last HBOT
      session. Sixteen diabetic patients and 16 control individual were included.
      Fasting glycemia was143.5 +/- 12.62 mg/dl in diabetic patients and 92.06 +/- 2.99
      mg/dl in controls. In diabetic patients glycemia post-OGTT was 280.25 +/- 22.29
      mg/dl before the first HBOT session. After 20 sessions, fasting and 2 h post-OGTT
      glycemia decreased significantly. In control group HBOT did not modify fasting
      glycemia and post-OGTT glycemia. Our results showed that HBOT ameliorates glucose
      tolerance in diabetic patients and suggest that HBOT could be used as a
      therapeutic intervention for type 2 diabetes. 

PMID- 26303485
TI  - Possible Role of TRP Channels in Rat Glomus Cells.
AB  - Carotid body (CB) glomus cells depolarize in response to hypoxia, causing a
      [Ca(2+)](i) increase, at least in part, through activation of voltage-dependent
      channels. Recently, Turner et al. (2013) showed that mouse glomus cells with
      knockout of TASK1/3(-/-) channels have near-normal [Ca(2+)](i) response to
      hypoxia. Thus, we postulated that TRP channels may provide an alternate calcium
      influx pathway which may be blocked by the TRP channel antagonist, 2-APB (2
      aminoethoxydiphenylborane). We confirmed that 2-APB inhibited the afferent nerve
      response to hypoxia, as previously reported (Lahiri S, Patel G, Baby S, Roy A
      (2009) 2-APB mediated effects on hypoxic calcium influx in rat carotid body
      glomus cells. FASEB 2009, Abstract, LB157; Kumar P, Pearson S, Gu Y (2006) A role
      for TRP channels in carotid body chemotransduction? FASEB J 20:A12-29). To
      examine the mechanism for this inhibition, we examined dissociated rat CB glomus
      cells for [Ca(2+)](i) responses to hypoxia, anoxia (with sodium dithionite), 20
      mM K(+), NaSH, NaCN, and FCCP in absence/presence of 2-APB (100 MUM). Also the
      effect of 2-APB on hypoxia and/or anoxia were investigated on NADH and
      mitochondria (MT) membrane potential. Our findings are as follows: (1) 2-APB
      significantly blocked the [Ca(2+)](i) increase in response to hypoxia and anoxia,
      but not the responses to 20 mM K(+). (2) The [Ca(2+)](i) responses NaSH, NaCN,
      and FCCP were significantly blocked by 2-APB. (3) Hypoxia-induced increases in
      NADH/NAD(+) and MT membrane depolarization were not effected by 2-APB. Thus TRP
      channels may provide an important pathway for calcium influx in glomus cells in
      response to hypoxia.

PMID- 26303486
TI  - Nitric Oxide Deficit Is Part of the Maladaptive Paracrine-Autocrine Response of
      the Carotid Body to Intermittent Hypoxia in Sleep Apnea.
AB  - The carotid body functions to maintain the blood gas homeostasis, whereas
      anomalous carotid chemoreceptor activities could be pathogenic in patients with
      sleep apnea. Recent findings suggest an upregulation of renin-angiotensin system
      (Lam SY, Liu Y, Ng KM et al. Exp Physiol 99:220-231, 2014), which could lead to
      inflammation in the carotid body during intermittent hypoxia (Lam SY, Liu Y, Ng
      KM et al. Histochem Cell Biol 137:303-317, 2012). In addition, the level of
      nitric oxide detected in the carotid body was significantly decreased following
      intermittent hypoxia for days. These locally regulated mechanisms are proposed to
      be a significant part of the hypoxia-mediated maladaptive changes of the carotid
      body, which could play a role in the pathophysiological cascade of sleep apnea in
      patients with an overactivity of the chemoreflex. 

PMID- 26303487
TI  - Respiratory Control in the mdx Mouse Model of Duchenne Muscular Dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is a genetic disease caused by defects in the
      dystrophin gene resulting in loss of the structural protein dystrophin. Patients
      have reduced diaphragm functional capacity due to progressive muscle weakness.
      Respiratory morbidity in DMD is further characterised by hypoxaemic periods due
      to hypoventilation. DMD patients die prematurely due to respiratory and cardiac
      failure. In this study, we examined respiratory function in young adult male mdx
      (dystrophin deficient) mice (C57BL/10ScSn-Dmd(mdx)/J; n = 10) and in wild-type
      controls (WT; C57BL/10ScSnJ; n = 11). Breathing was assessed in unrestrained,
      unanaesthetised animals by whole-body plethysmography. Ventilatory parameters
      were recorded during air breathing and during exposure to acute hypoxia (F(i)O(2)
      = 0.1, 20 min). Data for the two groups of animals were compared using Student's
      t tests. During normoxic breathing, mdx mice had reduced breathing frequency (p =
      0.011), tidal volume (p = 0.093) and minute ventilation (p = 0.033) compared to
      WT. Hypoxia increased minute ventilation in WT and mdx animals. Mdx mice had a
      significantly increased ventilatory response to hypoxia which manifest as an
      elevated % change from baseline for minute ventilation (p = 0.0015) compared to
      WT. We conclude that mdx mice have impaired normoxic ventilation suggestive of
      hypoventilation. Furthermore, mdx mice have an enhanced hypoxic ventilatory
      response compared to WT animals which we speculate may be secondary to chronic
      hypoxaemia. Our results indicate that a significant respiratory phenotype is
      evident as early as 8 weeks in the mdx mouse model of DMD.

PMID- 26303488
TI  - Mild Chronic Intermittent Hypoxia in Wistar Rats Evokes Significant
      Cardiovascular Pathophysiology but No Overt Changes in Carotid Body-Mediated
      Respiratory Responses.
AB  - Models of chronic intermittent hypoxia (CIH), the main feature of obstructive
      sleep apnoea (OSA), have demonstrated dysregulation of the cardiovascular and
      respiratory systems resulting in hypertension, cardiac hypertrophy and
      alterations in the hypoxic ventilatory response (HVR) due to changes in
      sympathetic and respiratory control by the carotid body. In the UK, treatment of
      OSA is only offered to patients with an apnoea-hypopnoea index (AHI) >15, we
      investigated whether mild CIH produced significant pathophysiological changes,
      which might inform treatment guidelines.Rats were exposed to CIH (6 h(-1), 8 h
      day(-1), 5 % O(2) nadir) for 2 weeks and then arterial blood pressure (ABP),
      heart rate (HR) and ventilation were recorded in these and normoxic control rats
      (N) under Alfaxan anaesthesia, at baseline and in response to Dejours test,
      graded hypoxia and hypercapnia. Hearts were analysed post-mortem.CIH induced
      significant increases in baseline ABP (142 +/- 5 vs 122 +/- 2 mmHg), HR (448 +/-
      9 vs 412 +/- 5 bpm) and cardiac mass (3.5 +/- 0.1 vs 2.7 +/- 0.1 g kg body mass(
      1)) as a result of a selective left ventricular hypertrophy (1.6 +/- 0.1 vs 1.3
      +/- 0.08 g kg body mass(-1); FCSA 464 +/- 32 MUm(2) vs 314 +/- 9 MUm(2)). There
      was no significant difference between N and CIH in baseline respiration or the
      response to Dejours test, graded hypoxia and hypercapnia.These results
      demonstrate that mild CIH can induce the significant cardiovascular changes
      associated with OSA without overt changes in respiratory function. Given evidence
      that CIH changes carotid body sensory activity, a possible explanation for these
      results is that there is differential integration of chemoreceptor input with
      respiratory and cardiac sympathetic outputs.

PMID- 26303489
TI  - Crucial Role of the Carotid Body Chemoreceptors on the Development of High
      Arterial Blood Pressure During Chronic Intermittent Hypoxia.
AB  - Exposure to chronic intermittent hypoxia (CIH), the main feature of obstructive
      sleep apnea, produces autonomic and cardiorespirartory alterations, and leads to
      systemic hypertension. These alterations are associated with enhanced carotid
      body (CB) chemosensory and ventilatory hypoxic reflexes and a decrease baroreflex
      (BRS) efficiency. The aim of this study was to determine the therapeutic effect
      of CB ablation on the elevated arterial blood pressure, the reduced BRS and the
      potentiated ventilatory response induced by CIH in conscious rats. Arterial blood
      pressure (BP) was continuous measured by telemetry in male Sprague-Dawley rats
      exposed to CIH (5 % O(2), 12 times/h, and 8 h/day). After 21 days of CIH, the CBs
      were selectively cryodestroyed, and rats were kept one more week in CIH.
      Ventilatory responses to hypoxia were assessed by whole body plethysmography and
      spontaneous BRS measured by the sequence method. Exposure to CIH produces
      hypertension, increased the chemoreflex ventilatory hypoxic responses, and
      decreased BRS. The ablation of the CBs normalized the elevated BP, and the
      altered ventilatory response and BRS. Present results suggest that the CB play a
      crucial role in the development of high arterial pressure and autonomic
      alterations induced by CIH.

PMID- 26303490
TI  - Relative Contribution of Nuclear and Membrane Progesterone Receptors in
      Respiratory Control.
AB  - Progesterone is a steroid hormone whose physiological effects can affect various
      systems, including reproductive, immune and cardiorespiratory systems. In fact,
      there are growing evidences proving that progesterone is potent respiratory
      stimulant with therapeutic value for sleep-disordered breathing. However there is
      no clear understanding of how progesterone mediates its stimulant respiratory
      effects and alleviates apnea. Mechanistically, it was demonstrated that this
      hormone elicits some of its respiratory effect via the classical mechanism of the
      nuclear progesterone receptor (nPR), a transcription factor belonging to the
      super family of steroid hormone receptors. Moreover, experimental results
      indicate that activation of alternative non-genomic (i.e. non-nuclear) signaling
      pathways such as the membrane progesterone receptors (mPR) could have a key role
      in the regulation of the respiratory control system. We provide preliminary
      results suggesting an important role of mPRbeta on respiratory control and
      ventilatory response to hypoxia in adult female mice. 

PMID- 26303491
TI  - Inhibition of Protein Kinases AKT and ERK1/2 Reduce the Carotid Body
      Chemoreceptor Response to Hypoxia in Adult Rats.
AB  - The carotid body is the main mammalian oxygen-sensing organ regulating
      ventilation. Despite the carotid body is subjected of extensive anatomical and
      functional studies, little is yet known about the molecular pathways signaling
      the neurotransmission and neuromodulation of the chemoreflex activity. As kinases
      are molecules widely involved in motioning a broad number of neural processes,
      here we hypothesized that pathways of protein kinase B (AKT) and extracellular
      signal-regulated kinases 1/2 (ERK1/2) are implicated in the carotid body response
      to hypoxia. This hypothesis was tested using the in-vitro carotid body/carotid
      sinus nerve preparation ("en bloc") from Sprague Dawley adult rats. Preparations
      were incubated for 60 min in tyrode perfusion solution (control) or containing 1
      MUM of LY294002 (AKT inhibitor), or 1 MUM of UO-126 (ERK1/2 inhibitor). The
      carotid sinus nerve chemoreceptor discharge rate was recorded under baseline
      (perfusion solution bubbled with 5 % CO(2) balanced in O(2)) and hypoxic
      (perfusion solution bubbled with 5 % CO(2) balanced in N(2)) conditions. Compared
      to control, both inhibitors significantly decreased the normoxic and hypoxic
      carotid body chemoreceptor activity. LY294002- reduced carotid sinus nerve
      discharge rate in hypoxia by about 20 %, while UO-126 reduces the hypoxic
      response by 45 %. We concluded that both AKT and ERK1/2 pathways are crucial for
      the carotid body intracellular signaling process in response to hypoxia.

PMID- 26303492
TI  - Ecto-5'-Nucleotidase, Adenosine and Transmembrane Adenylyl Cyclase Signalling
      Regulate Basal Carotid Body Chemoafferent Outflow and Establish the Sensitivity
      to Hypercapnia.
AB  - Carotid body (CB) stimulation by hypercapnia causes a reflex increase in
      ventilation and, along with the central chemoreceptors, this prevents a
      potentially lethal systemic acidosis. Control over the CB chemoafferent output
      during normocapnia and hypercapnia most likely involves multiple
      neurotransmitters and neuromodulators including ATP, acetylcholine, dopamine,
      serotonin and adenosine, but the precise role of each is yet to be fully
      established. In the present study, recordings of chemoafferent discharge
      frequency were made from the isolated in vitro CB in order to determine the
      contribution of adenosine, derived specifically from extracellular catabolism of
      ATP, in mediating basal chemoafferent activity and responses to hypercapnia.
      Pharmacological inhibition of ecto-5'-nucleotidase (CD73), a key enzyme required
      for extracellular generation of adenosine from ATP, using alpha,beta-methylene
      ADP, virtually abolished the basal normocapnic single fibre discharge frequency
      (superfusate PO(2) ~ 300 mmHg, PCO(2) ~ 40 mmHg) and diminished the chemoafferent
      response to hypercapnia (PCO(2) ~ 80 mmHg). These effects were mimicked by the
      blockade of adenosine receptors with 8-(p-sulfophenyl) theophylline. The
      excitatory impact of adenosinergic signalling on CB hypercapnic sensitivity is
      most likely to be conferred through changes in cAMP. Here, inhibition of
      transmembrane, but not soluble adenylate cyclases, reduced normocapnic single
      fibre activity and inhibited the elevation evoked by hypercapnia by approximately
      50 %. These data therefore identify a functional role for CD73 derived adenosine
      and transmembrane adenylate cyclases, in modulating the basal chemoafferent
      discharge frequency and in priming the CB to hypercapnic stimulation.

PMID- 26303493
TI  - T-Type Ca2+ Channel Regulation by CO: A Mechanism for Control of Cell
      Proliferation.
AB  - T-type Ca(2+) channels regulate proliferation in a number of tissue types,
      including vascular smooth muscle and various cancers. In such tissues, up
      regulation of the inducible enzyme heme oxygenase-1 (HO-1) is often observed, and
      hypoxia is a key factor in its induction. HO-1 degrades heme to generate carbon
      monoxide (CO) along with Fe(2+) and biliverdin. Since CO is increasingly
      recognized as a regulator of ion channels (Peers et al. 2015), we have explored
      the possibility that it may regulate proliferation via modulation of T-type
      Ca(2+) channels.Whole-cell patch-clamp recordings revealed that CO (applied as
      the dissolved gas or via CORM donors) inhibited all 3 isoforms of T-type Ca(2+)
      channels (Cav3.1-3.3) when expressed in HEK293 cells with similar IC(50) values,
      and induction of HO-1 expression also suppressed T-type currents (Boycott et al.
      2013). CO/HO-1 induction also suppressed the elevated basal [Ca(2+) ](i) in cells
      expressing these channels and reduced their proliferative rate to levels seen in
      non-transfected control cells (Duckles et al. 2015).Proliferation of vascular
      smooth muscle cells (both A7r5 and human saphenous vein cells) was also
      suppressed either by T-type Ca(2+) channel inhibitors (mibefradil and NNC 55
      0396), HO-1 induction or application of CO. Effects of these blockers and CO were
      non additive. Although L-type Ca(2+) channels were also sensitive to CO (Scragg
      et al. 2008), they did not influence proliferation. Our data suggest that HO-1
      acts to control proliferation via CO modulation of T-type Ca(2+) channels.

PMID- 26303494
TI  - Glutamatergic Receptor Activation in the Commisural Nucleus Tractus Solitarii
      (cNTS) Mediates Brain Glucose Retention (BGR) Response to Anoxic Carotid
      Chemoreceptor (CChr) Stimulation in Rats.
AB  - Glutamate, released from central terminals of glossopharyngeal nerve, is a major
      excitatory neurotransmitter of commissural nucleus tractus solitarii (cNTS)
      afferent terminals, and brain derived neurotrophic factor (BDNF) has been shown
      to attenuate glutamatergic AMPA currents in NTS neurons. To test the hypothesis
      that AMPA contributes to glucose regulation in vivo modulating the hyperglycemic
      reflex with brain glucose retention (BGR), we microinjected AMPA and NBQX (AMPA
      antagonist) into the cNTS before carotid chemoreceptor stimulation in
      anesthetized normal Wistar rats, while hyperglycemic reflex an brain glucose
      retention (BGR) were analyzed. To investigate the underlying mechanisms, GluR2/3
      receptor and c-Fos protein expressions in cNTS neurons were determined. We showed
      that AMPA in the cNTS before CChr stimulation inhibited BGR observed in aCSF
      group. In contrast, NBQX in similar conditions, did not modify the effects on
      glucose variables observed in aCSF control group. These experiments suggest that
      glutamatergic pathways, via AMPA receptors, in the cNTS may play a role in
      glucose homeostasis. 

PMID- 26303495
TI  - Augmented 5-HT Secretion in Pulmonary Neuroepithelial Bodies from PHD1 Null Mice.
AB  - Sustained exposure to low oxygen concentration leads to profound changes in gene
      expression to restore oxygen homeostasis. Hypoxia-inducible factors (HIFs)
      comprise a group of transcription factors which accumulate under hypoxia and
      contribute to the complex changes in gene expression. Under normoxic conditions
      HIFs are degraded by prolyl-hydroxylases (PHD), however during hypoxia this
      degradation is inhibited causing HIF accumulation and subsequent changes in gene
      expression. Pulmonary neuroepithelial bodies (NEB) are innervated serotonin (5
      HT)-producing cells distributed throughout the airway epithelium. These putative
      O(2) sensors are hypothesized to contribute to the ventilatory response to
      hypoxia. NEB dysfunction has been implicated in several paediatric lung diseases
      including neuroendocrine cell hyperplasia of infancy and sudden infant death
      syndrome, both characterized by a marked NEB hyperplasia with unknown functional
      significance. We have previously reported striking NEB hyperplasia in PHD1(-/-)
      mice making these mice a potential model to study the role of NEBs in paediatric
      lung diseases. Here we report in vitro studies on 5-HT release from NEB using
      this model.

PMID- 26303496
TI  - Selective Expression of Galanin in Neuronal-Like Cells of the Human Carotid Body.
AB  - The carotid body is a neural-crest-derived organ devoted to respiratory
      homeostasis through sensing changes in blood oxygen levels. The sensory units are
      the glomeruli composed of clusters of neuronal-like (type I) cells surrounded by
      glial-like (type II) cells. During chronic hypoxia, the carotid body shows
      growth, with increasing neuronal-like cell numbers. We are interested in the
      signals involved in the mechanisms that underlie such response, because they are
      not well understood and described. Considering that, in literature, galanin is
      involved in neurotrophic or neuroprotective role in cell proliferation and is
      expressed in animal carotid body, we investigated its expression in human. Here,
      we have shown the expression and localisation of galanin in the human carotid
      body. 

PMID- 26303497
TI  - Role of BK Channels in Murine Carotid Body Neural Responses in vivo.
AB  - The aim of this study was to explore the role of BK channels in the hypoxic
      sensitivity of the in vivo murine carotid body (CB). Four strains of mice
      (DBA/2J, A/J, BKalpha1 knockout and BKalpha1 wild type - FVB background) were
      used. The mice were anesthetized, paralyzed and mechanically ventilated (PaCO(2)
      ~ 35 mmHg, PO(2) > 300 mmHg). We measured carotid sinus nerve (CSN) activity
      during three gas challenges (F(I)O(2): 0.21, 0.15 and 0.10). CSN activity was
      analyzed with time-variant spectral analysis with frequency domain conversion
      (Fast Fourier Transforms). Afferent CSN activity increased with lowering F(I)O(2)
      in the DBA/2J, BKKO and BKWT mice with the most robust response in 600-800
      frequencies. No substantial changes were observed in the A/J mice. Although
      maximal neural output was similar between the BKKO and BKWT mice, the BKWT had a
      higher early response compared to BKKO. Thus, BK channels may play a role in the
      initial response of the CB to hypoxia. The contribution of BKbeta subunits or the
      importance of frequency specific responses was unable to be determined by the
      current study.

PMID- 26303498
TI  - Chronic Intermittent Hypoxia Blunts the Expression of Ventilatory Long Term
      Facilitation in Sleeping Rats.
AB  - We have previously reported that chronic intermittent hypoxia (CIH), a central
      feature of human sleep-disordered breathing, causes respiratory instability in
      sleeping rats (Edge D, Bradford A, O'halloran KD. Adv Exp Med Biol 758:359-363,
      2012). Long term facilitation (LTF) of respiratory motor outputs following
      exposure to episodic, but not sustained, hypoxia has been described. We
      hypothesized that CIH would enhance ventilatory LTF during sleep. We examined the
      effects of 3 and 7 days of CIH exposure on the expression of ventilatory LTF in
      sleeping rats. Adult male Wistar rats were exposed to 20 cycles of normoxia and
      hypoxia (5 % O(2) at nadir; SaO(2) ~ 80 %) per hour, 8 h per day for 3 or 7
      consecutive days (CIH, N = 7 per group). Corresponding sham groups (N = 7 per
      group) were subjected to alternating cycles of air under identical experimental
      conditions in parallel. Following gas exposures, breathing during sleep was
      assessed in unrestrained, unanaesthetized animals using the technique of whole
      body plethysmography. Rats were exposed to room air (baseline) and then to an
      acute IH (AIH) protocol consisting of alternating periods of normoxia (7 min) and
      hypoxia (FiO(2) 0.1, 5 min) for 10 cycles. Breathing was monitored during the AIH
      exposure and for 1 h in normoxia following AIH exposure. Baseline ventilation was
      elevated after 3 but not 7 days of CIH exposure. The hypoxic ventilatory response
      was equivalent in sham and CIH animals after 3 days but ventilatory responses to
      repeated hypoxic challenges were significantly blunted following 7 days of CIH.
      Minute ventilation was significantly elevated following AIH exposure compared to
      baseline in sham but not in CIH exposed animals. LTF, determined as the %
      increase in minute ventilation from baseline following AIH exposure, was
      significantly blunted in CIH exposed rats. In summary, CIH leads to impaired
      ventilatory responsiveness to AIH. Moreover, CIH blunts ventilatory LTF. The
      physiological significance of ventilatory LTF is context-dependent but it is
      reasonable to consider that it can potentially destabilize respiratory control,
      in view of the potential for LTF to give rise to hypocapnia. CIH-induced blunting
      of LTF may represent a compensatory mechanism subserving respiratory homeostasis.
      Our results suggest that CIH-induced increase in apnoea index (Edge D, Bradford
      A, O'halloran KD. Adv Exp Med Biol 758:359-363, 2012) is not related to enhanced
      ventilatory LTF. We conclude that the mature adult respiratory system exhibits
      plasticity and metaplasticity with potential consequences for the control of
      respiratory homeostasis. Our results may have implications for human sleep
      apnoea.

PMID- 26303499
TI  - Heme Oxygenase-1 Influences Apoptosis via CO-mediated Inhibition of K+ Channels.
AB  - Hypoxic/ischemic episodes can trigger oxidative stress-mediated loss of central
      neurons via apoptosis, and low pO2 is also a feature of the tumor
      microenvironment, where cancer cells are particularly resistant to apoptosis. In
      the CNS, ischemic insult increases expression of the CO-generating enzyme heme
      oxygenase-1 (HO-1), which is commonly constitutively active in cancer cells. It
      has been proposed that apoptosis can be regulated by the trafficking and activity
      of K(+) channels, particularly Kv2.1. We have explored the idea that HO-1 may
      influence apoptosis via regulation of Kv2.1. Overexpression of Kv2.1 in HEK293
      cells increased their vulnerability to oxidant-induced apoptosis. CO (applied as
      the donor CORM-2) protected cells against apoptosis and inhibited Kv2.1 channels.
      Similarly in hippocampal neurones, CO selectively inhibited Kv2.1 and protected
      neurones against oxidant-induced apoptosis. In medulloblastoma sections we
      identified constitutive expression of HO-1 and Kv2.1, and in the medulloblastoma
      derived cell line DAOY, hypoxic HO-1 induction or exposure to CO protected cells
      against apoptosis, and also selectively inhibited Kv2.1 channels expressed in
      these cells. These studies are consistent with a central role for Kv2.1 in
      apoptosis in both central neurones and cancer cells. They also suggest that HO-1
      expression can strongly influence apoptosis via CO-mediated regulation of Kv2.1
      activity. 

PMID- 26303500
TI  - Inhibition of T-type Ca2+ Channels by Hydrogen Sulfide.
AB  - T-type Ca(2+) channels are a distinct family of low voltage-activated Ca(2+)
      channels which serve many roles in different tissues. Several studies have
      implicated them, for example, in the adaptive responses to chronic hypoxia in the
      cardiovascular and endocrine systems. Hydrogen sulfide (H(2)S) was more recently
      discovered as an important signalling molecule involved in many functions,
      including O(2) sensing. Since ion channels are emerging as an important family of
      target proteins for modulation by H(2)S, and both T-type Ca(2+) channels and
      H(2)S are involved in cellular responses to hypoxia, we have investigated whether
      recombinant and native T-type Ca(2+) channels are a target for modulation by
      H(2)S. Using patch-clamp electrophysiology, we demonstrate that the H(2)S donor,
      NaHS, selectively inhibits Cav3.2 T-type Ca(2+) channels heterologously expressed
      in HEK293 cells, whilst Cav3.1 and Cav3.3 channels were unaffected. Sensitivity
      of Cav3.2 channels to H2S required the presence of the redox-sensitive
      extracellular residue H191, which is also required for tonic binding of Zn(2+) to
      this channel. Chelation of Zn(2+) using TPEN prevented channel inhibition by
      H(2)S. H2S also selectively inhibited native T-type channels (primarily Cav3.2)
      in sensory dorsal root ganglion neurons. Our data demonstrate a novel target for
      H(2)S regulation, the T-type Ca(2+) channel Cav3.2. Results have important
      implications for the proposed pro-nociceptive effects of this gasotransmitter.
      Implications for the control of cellular responses to hypoxia await further
      study.

PMID- 26303501
TI  - GAL-021 and GAL-160 are Efficacious in Rat Models of Obstructive and Central
      Sleep Apnea and Inhibit BKCa in Isolated Rat Carotid Body Glomus Cells.
AB  - GAL-021 and GAL-160 are alkylamino triazine analogues, which stimulate
      ventilation in rodents, non-human primates and (for GAL-021) in humans. To probe
      the site and mechanism of action of GAL-021 and GAL-160 we utilized spirometry in
      urethane anesthetized rats subjected to acute bilateral carotid sinus nerve
      transection (CSNTX) or sham surgery. In addition, using patch clamp
      electrophysiology we evaluated ionic currents in carotid body glomus cells
      isolated from neonatal rats. Acute CSNTX markedly attenuated and in some
      instances abolished the ventilatory stimulant effects of GAL-021 and GAL-160 (0.3
      mg/kg IV), suggesting the carotid body is a/the major locus of action.
      Electrophysiology studies, in isolated Type I cells, established that GAL-021 (30
      MUM) and GAL-160 (30 MUM) inhibited the BK(Ca) current without affecting the
      delayed rectifier K(+), leak K(+) or inward Ca(2+) currents. At a higher
      concentration of GAL-160 (100 MUM), inhibition of the delayed rectifier K(+)
      current and leak K(+) current were observed. These data are consistent with the
      concept that GAL-021 and GAL-160 influence breathing control by acting as
      peripheral chemoreceptor modulators predominantly by inhibiting BK(Ca) mediated
      currents in glomus cells of the carotid body.

PMID- 26303502
TI  - The Human Carotid Body Gene Expression and Function in Signaling of Hypoxia and
      Inflammation.
AB  - Although animal carotid body oxygen sensing and signaling has been extensively
      investigated, the human carotid body remains essentially uncharacterized.
      Therefore, we aimed to study the human carotid body in terms of morphology,
      global and specific expression of sensing and signaling genes as well as
      inflammatory genes. The human carotid body response to brief or prolonged hypoxia
      was studied in carotid body slices from adult surgical patients and ACh, ATP and
      cytokine release was analyzed. We demonstrate that the human carotid body
      expresses key oxygen sensing and signaling genes in similarity with animal
      carotid bodies with a few diverging data. The human carotid body moreover shows
      enrichment of genes in the inflammatory response and releases pro and anti
      inflammatory cytokines in response to prolonged hypoxia. In response to acute
      hypoxia the human carotid body releases ACh and ATP and we thus translate
      previous findings in animal models to human tissue. We conclude that by releasing
      pro- and anti-inflammatory cytokines during hypoxia the human carotid body
      displays a structural and functional capacity to participate in sensing and
      mediating systemic inflammation. 

PMID- 26303503
TI  - The Carotid Body Does Not Mediate the Acute Ventilatory Effects of Leptin.
AB  - Leptin is a hormone produced mostly in adipose tissue and playing a key role in
      the control of feeding and energy expenditure aiming to maintain a balance
      between food intake and metabolic activity. In recent years, it has been
      described that leptin might also contributes to control ventilation as the
      administration of the hormone reverses the hypoxia and hypercapnia commonly
      encountered in ob/ob mice which show absence of the functional hormone. In
      addition, it has been shown that the carotid body (CB) of the rat expresses
      leptin as well as the functional leptin-B receptor. Therefore, the possibility
      exists that the ventilatory effects of leptin are mediated by the CB
      chemoreceptors. In the experiments described below we confirm the stimulatory
      effect of leptin on ventilation, finding additionally that the CB does not
      mediate the instant to instant control of ventilation. 

PMID- 26303504
TI  - Oxidative stress and endocytosis are involved in upregulation of interleukin-8
      expression in airway cells exposed to PM2.5.
AB  - Inhaled PM2.5 (particulate matter with an aerodynamic diameter of 2.5 MUm or
      less) can induce lung inflammation through released inflammatory mediators from
      airway cells, such as interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF
      alpha). However, the mechanisms underlying PM2.5-induced IL-8 gene expression
      have not been fully characterized. BEAS-2B cells (a human bronchial epithelial
      cell line) and THP-1 cells (a human macrophage-like cell line) were used as the
      in vitro models to investigate the underlying mechanism in this study. IL-8
      expression was increased in the cells treated with PM2.5 in a dose-dependent
      manner. The water-soluble and insoluble fractions of PM2.5 suspension were both
      shown to induce IL-8 expression. PM2.5 exposure could obviously induce ROS
      (reactive oxygen species) generation, indicative of oxidative stress.
      Pretreatment with the antioxidant N-acetyl-l-cysteine (NAC) potently inhibited
      PM2.5-induced IL-8 expression. Employment of the transition metal chelators
      including TPEN (N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine) or DFO
      (desferrioxamine) inhibited IL-8 expression induced by PM2.5 by over 20% in BEAS
      2B cells, but had minimal effect in THP-1 cells. Pretreatment with the
      endocytosis inhibitor CytD markedly blocked IL-8 expression induced by PM2.5 in
      both BEAS-2B and THP-1 cells. In summary, exposure to PM2.5 induced IL-8 gene
      expression through oxidative stress induction and endocytosis in airway cells.
      (c) 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1869-1878, 2016.

PMID- 26303505
TI  - Adoption and maintenance of gym-based strength training in the community setting
      in adults with excess weight or type 2 diabetes: a randomized controlled trial.
AB  - BACKGROUND: Participant adoption and maintenance is a major challenge in strength
      training (ST) programs in the community-setting. In adults who were overweight or
      with type 2 diabetes (T2DM), the aim of this study was to compare the
      effectiveness of a standard ST program (SST) to an enhanced program (EST) on the
      adoption and maintenance of ST and cardio-metabolic risk factors and muscle
      strength. METHODS: A 12-month cluster-randomized controlled trial consisting of a
      6-month adoption phase followed by a 6-month maintenance phase. In 2008-2009, men
      and women aged 40-75 years (n = 318) with T2DM (n = 117) or a BMI >25 (n = 201)
      who had not participated in ST previously were randomized into either a SST or an
      EST program (which included additional motivationally-tailored behavioral
      counselling). Adoption and maintenance were defined as undertaking >= 3 weekly
      gym-based exercise sessions during the first 6-months and from 6-12 months
      respectively and were assessed using a modified version of the CHAMPS (Community
      Healthy Activity Models Program for Seniors) instrument. RESULTS: Relative to the
      SST group, the adjusted odds ratio (OR) of adopting ST for all participants in
      the EST group was 3.3 (95 % CI 1.2 to 9.4). In stratified analyses including only
      those with T2DM, relative to the SST group, the adjusted OR of adopting ST in the
      EST group was 8.2 (95 % CI 1.5-45.5). No significant between-group differences
      were observed for maintenance of ST in either pooled or stratified analyses. In
      those with T2DM, there was a significant reduction in HbA1c in the EST compared
      to SST group during the adoption phase (net difference, -0.13 % [-0.26 to 
      0.01]), which persisted after 12-months (-0.17 % [-0.3 to -0.05]). CONCLUSIONS: A
      behaviorally-focused community-based EST intervention was more effective than a
      SST program for the adoption of ST in adults with excess weight or T2DM and led
      to greater improvements in glycemic control in those with T2DM. TRIAL
      REGISTRATION: Registered at ACTRN12611000695909 (Date registered 7/7/2011).

PMID- 26303506
TI  - A Commentary on the Need for 3D-Biologically Relevant In Vitro Environments to
      Investigate Astrocytes and Their Role in Central Nervous System Inflammation.
AB  - Astrocytes execute essential functions in the healthy CNS, whilst also being
      implicated as a limitation to functional regeneration and repair after injury.
      They respond to injury to minimize damage to healthy tissue whilst also
      attempting to seal the broken blood-brain-barrier, however, they impede recovery
      if they are persistent and form a permanent scar in the injured brain. As such,
      it is of great importance to understand the mechanism underlying the astrocytic
      response to injury, and this understanding is currently limited by the in vitro
      environments available to scientists. Biomaterials such as nanofibres and
      hydrogels offer great potential for the development of superior, 3D cell culture
      environments in which to study astrocyte behavior and phenotype. The
      implementation of such in vitro environments with a particularly
      interdisciplinary approach can improve the field's understanding of astrocytes,
      their role in central nervous system inflammation, and elucidate potential
      strategies to achieve functional regeneration. 

PMID- 26303507
TI  - The Split Personality of Glutamate Transporters: A Chloride Channel and a
      Transporter.
AB  - Transporters and ion channels are conventionally categorised into distinct
      classes of membrane proteins. However, some membrane proteins have a split
      personality and can function as both transporters and ion channels. The
      excitatory amino acid transporters (EAATs) in particular, function as both
      glutamate transporters and chloride (Cl(-)) channels. The EAATs couple the
      transport of glutamate to the co-transport of three Na(+) ions and one H(+) ion
      into the cell, and the counter-transport of one K(+) ion out of the cell. The
      EAAT Cl(-) channel is activated by the binding of glutamate and Na(+), but is
      thermodynamically uncoupled from glutamate transport and involves molecular
      determinants distinct from those responsible for glutamate transport. Several
      crystal structures of an EAAT archaeal homologue, GltPh, at different stages of
      the transport cycle, alongside numerous functional studies and molecular dynamics
      simulations, have provided extensive insights into the mechanism of substrate
      transport via these transporters. However, the molecular determinants involved in
      Cl(-) permeation, and the mechanism by which this channel is activated are not
      entirely understood. Here we will discuss what is currently known about the
      molecular determinants involved in EAAT-mediated Cl(-) permeation and the
      mechanisms that underlie their split personality. 

PMID- 26303508
TI  - The Ketone Body, beta-Hydroxybutyrate Stimulates the Autophagic Flux and Prevents
      Neuronal Death Induced by Glucose Deprivation in Cortical Cultured Neurons.
AB  - Glucose is the major energy substrate in brain, however, during ketogenesis
      induced by starvation or prolonged hypoglycemia, the ketone bodies (KB),
      acetoacetate and beta-hydroxybutyrate (BHB) can substitute for glucose. KB
      improve neuronal survival in diverse injury models, but the mechanisms by which
      KB prevent neuronal damage are still not well understood. In the present study we
      have investigated whether protection by the D isomer of BHB (D-BHB) against
      neuronal death induced by glucose deprivation (GD), is related to autophagy.
      Autophagy is a lysosomal-dependent degradation process activated during
      nutritional stress, which leads to the digestion of damaged proteins and
      organelles providing energy for cell survival. Results show that autophagy is
      activated in cortical cultured neurons during GD, as indicated by the increase in
      the levels of the lipidated form of the microtubule associated protein light
      chain 3 (LC3-II), and the number of autophagic vesicles. At early phases of
      glucose reintroduction (GR), the levels of p62 declined suggesting that the
      degradation of the autophagolysosomal content takes place at this time. In
      cultures exposed to GD and GR in the presence of D-BHB, the levels of LC3-II and
      p62 rapidly declined and remained low during GR, suggesting that the KB
      stimulates the autophagic flux preventing autophagosome accumulation and
      improving neuronal survival. 

PMID- 26303509
TI  - Up-Regulation of KPNB1 Involves in Neuronal Apoptosis Following Intracerebral
      Hemorrhage in Adult Rats.
AB  - Kpnb1, also known as Importin beta1, is a member of the Karyopherin protein
      family which plays a important role in nuclear import and export pathways. Its
      expression has been shown to be responsive to stress, such as heat shock, ethanol
      and oxidative stress. Previous studies demonstrated that Kpnb1 had anti-apoptotic
      in cervical cancer. These together prompted us to explore whether Kpnb1 has some
      association with neuron apoptosis in the pathophysiology of intracerebral
      hemorrhage (ICH). In our study, an ICH model was established by injecting into
      the right basal ganglia of adult rats with their autologous whole blood and
      assessed by behavioral tests. We found Kpnb1 were significantly up-regulated
      adjacent to the hematoma following ICH by Western blot and immunohistochemistry.
      Double immunofluorenscence manifested Kpnb1 was strikingly increased in neurons,
      not astrocytes or microglia. Furthermore, we also found that kpnb1 had co
      localizations with active-caspase-3 which is a neuronal apoptosis marker
      suggesting its role in neuronal apoptosis. What's more, our in vitro study, using
      Kpnb1 RNA interference in PC12 cells, further indicated that Kpnb1 might exert
      its pro-apoptotic function on neuronal apoptosis. Therefore, Kpnb1 may play a
      role in the neuronal apoptosis following ICH. 

PMID- 26303510
TI  - Analysis of dynamic cantilever behavior in tapping mode atomic force microscopy.
AB  - Tapping mode atomic force microscopy (AFM) provides phase images in addition to
      height and amplitude images. Although the behavior of tapping mode AFM has been
      investigated using mathematical modeling, comprehensive understanding of the
      behavior of tapping mode AFM still poses a significant challenge to the AFM
      community, involving issues such as the correct interpretation of the phase
      images. In this paper, the cantilever's dynamic behavior in tapping mode AFM is
      studied through a three dimensional finite element method. The cantilever's
      dynamic displacement responses are firstly obtained via simulation under
      different tip-sample separations, and for different tip-sample interaction
      forces, such as elastic force, adhesion force, viscosity force, and the van der
      Waals force, which correspond to the cantilever's action upon various different
      representative computer-generated test samples. Simulated results show that the
      dynamic cantilever displacement response can be divided into three zones: a free
      vibration zone, a transition zone, and a contact vibration zone. Phase
      trajectory, phase shift, transition time, pseudo stable amplitude, and frequency
      changes are then analyzed from the dynamic displacement responses that are
      obtained. Finally, experiments are carried out on a real AFM system to support
      the findings of the simulations.

PMID- 26303511
TI  - The N-Terminal Peptides of the Three Human Isoforms of the Mitochondrial Voltage
      Dependent Anion Channel Have Different Helical Propensities.
AB  - The voltage-dependent anion channel (VDAC) is the main mitochondrial porin
      allowing the exchange of ions and metabolites between the cytosol and the
      mitochondrion. In addition, VDAC was found to actively interact with proteins
      playing a fundamental role in the regulation of apoptosis and being of central
      interest in cancer research. VDAC is a large transmembrane beta-barrel channel,
      whose N-terminal helical fragment adheres to the channel interior, partially
      closing the pore. This fragment is considered to play a key role in protein
      stability and function as well as in the interaction with apoptosis-related
      proteins. Three VDAC isoforms are differently expressed in higher eukaryotes, for
      which distinct and complementary roles are proposed. In this work, the folding
      propensity of their N-terminal fragments has been compared. By using multiple
      spectroscopic techniques, and complementing the experimental results with
      theoretical computer-assisted approaches, we have characterized their
      conformational equilibrium. Significant differences were found in the intrinsic
      helical propensity of the three peptides, decreasing in the following order:
      hVDAC2 > hVDAC3 > hVDAC1. In light of the models proposed in the literature to
      explain voltage gating, selectivity, and permeability, as well as interactions
      with functionally related proteins, our results suggest that the different
      chemicophysical properties of the N-terminal domain are possibly correlated to
      different functions for the three isoforms. The overall emerging picture is that
      a similar transmembrane water accessible conduit has been equipped with not
      identical domains, whose differences can modulate the functional roles of the
      three VDAC isoforms. 

PMID- 26303513
TI  - Primary Persistent Atrial Fibrillation: A Distinct Arrhythmia Subentity of an
      Ablation Population.
AB  - INTRODUCTION: Persistent atrial fibrillation (persAF) can occur either as a
      sustained arrhythmia that has progressed from initially paroxysmal AF or as
      primary persAF without a history of any spontaneously terminated episode. There
      is a paucity of data differentiating between the 2 different persAF entities.
      Thus, we prospectively evaluated baseline characteristics, electrophysiological
      features, and ablation outcome in these 2 patient cohorts. METHODS AND RESULTS: A
      total number of 154 consecutive persAF patients (63 +/- 10 years, f = 42,
      longstanding persAF = 60) were characterized in terms of having primary persAF (P
      persAF group) or persAF that secondarily progressed from paroxysmal AF (S-persAF
      group). All patients underwent de novo catheter ablation using the stepwise
      approach. PersAF entities were characterized by detailed patient history,
      sequential Holter monitoring, and reports of documented modes of AF conversion,
      respectively. The P-persAF group had a higher number of young patients (<50
      years), a shorter AF history, and a higher number of congestive heart failure.
      The HATCH score did not differ between the groups. Procedural AF termination rate
      was significantly higher in S-persAF than in P-persAF patients (n = 55 [81%] vs.
      n = 58 [68%], P = 0.043). At 1-year follow-up, the arrhythmia-free survival after
      a single procedure was significantly lower in patients with P-persAF (26% vs.
      43%, P = 0.016). Categorization to P-persAF was the strongest independent
      predictor of arrhythmia recurrence. CONCLUSIONS: P-persAF seems to be a specific
      arrhythmia entity that is associated with a lower AF-termination rate and a worse
      outcome after catheter ablation as compared to S-persAF.

PMID- 26303514
TI  - Fetus papyraceus causing dystocia in a rural setting: a case report.
AB  - INTRODUCTION: Fetus papyraceus is a rare condition which describes a mummified
      fetus in a multiple gestation pregnancy in which one fetus dies and becomes
      flattened between the membranes of the other fetus and uterine wall. We report a
      case of fetus papyraceus diagnosed during labor as a result of arrested descent.
      CASE PRESENTATION: A 23-year-old Sukuma woman, gravida 2, para 1 presented to an
      maternity emergency unit of Sengerema Designated District hospital at a gestation
      age of 35(+5) weeks as a referral from a rural health center due to arrested
      descent despite being in active labor for the past 8 hours. On vaginal
      examination, her cervix was 6cm dilated; fully effaced, presenting part was at
      station -3. A sharp and solid object-like thing was felt on the right side of her
      cervix. Due to uncertainty of the presenting part together with arrested descent,
      a decision was reached to deliver her by caesarean section. A twin gestation was
      identified during caesarean section: one being a male baby in cephalic
      presentation, weighing 1.9kg with Apgar score 8 in first minute and 9 in fifth
      minute with its own normal placenta and membranes. There was another atrophied
      placenta with calcifications without a cord and with mummified fetal bones on the
      anterior to the lower segment at the level of the internal orifice of the uterus.
      The atrophied placenta and mummified fetal bones weighed 200gms. One unit of
      blood was transfused intraoperatively due to severe anemia prior to surgery. Both
      the mother and the baby were discharged home in good condition. CONCLUSIONS: The
      primary concern for fetus papyraceus is its effect on the surviving fetus and on
      the mother. To avoid possible complications, the intrauterine diagnosis of fetus
      papyraceus by serial ultrasound examinations and routine placental examination to
      search for fetus papyraceus is mandatory.

PMID- 26303512
TI  - Chromatin states and nuclear organization in development--a view from the nuclear
      lamina.
AB  - The spatial distribution of chromatin domains in interphase nuclei changes
      dramatically during development in multicellular organisms. A crucial question is
      whether nuclear organization is a cause or a result of differentiation. Genetic
      perturbation of lamina-heterochromatin interactions is helping to reveal the
      cross-talk between chromatin states and nuclear organization. 

PMID- 26303516
TI  - Marine amoebae with cytoplasmic and perinuclear symbionts deeply branching in the
      Gammaproteobacteria.
AB  - Amoebae play an important ecological role as predators in microbial communities.
      They also serve as niche for bacterial replication, harbor endosymbiotic bacteria
      and have contributed to the evolution of major human pathogens. Despite their
      high diversity, marine amoebae and their association with bacteria are poorly
      understood. Here we describe the isolation and characterization of two novel
      marine amoebae together with their bacterial endosymbionts, tentatively named
      'Candidatus Occultobacter vannellae' and 'Candidatus Nucleophilum amoebae'. While
      one amoeba strain is related to Vannella, a genus common in marine habitats, the
      other represents a novel lineage in the Amoebozoa. The endosymbionts showed only
      low similarity to known bacteria (85-88% 16S rRNA sequence similarity) but
      together with other uncultured marine bacteria form a sister clade to the
      Coxiellaceae. Using fluorescence in situ hybridization and transmission electron
      microscopy, identity and intracellular location of both symbionts were confirmed;
      one was replicating in host-derived vacuoles, whereas the other was located in
      the perinuclear space of its amoeba host. This study sheds for the first time
      light on a so far neglected group of protists and their bacterial symbionts. The
      newly isolated strains represent easily maintainable model systems and pave the
      way for further studies on marine associations between amoebae and bacterial
      symbionts. 

PMID- 26303517
TI  - Transformation of IGHV4-34+ hairy cell leukaemia-variant with U2AF1 mutation into
      a clonally-related high grade B-cell lymphoma responding to immunochemotherapy.

PMID- 26303518
TI  - Design and preliminary testing of a novel skin expander for total ear
      reconstruction in a rabbit model.
AB  - BACKGROUND: Ear reconstruction is one of the most complicated and challenging
      techniques in plastic surgery because of the histologic and anatomic properties
      of the ear. Success depends on fitting the auriform cartilage scaffold into the
      overlying skin, but current approaches can just give results that are not
      lifelike and can lead to complications. MATERIALS AND METHODS: A novel double
      capsule, double-valve plastic ear expander was designed and implanted
      subcutaneously on either side of the dorsum of six New Zealand white rabbits (two
      expanders per rabbit). The outer capsule was expanded by injecting approximately
      120 mL of physiological saline, then withdrawing the liquid on two occasions.
      Next, the ear-shaped inner capsule was filled with high-hardness plaster, and the
      external capsule was emptied such that the expanded skin flap and external
      capsule responded to the negative pressure and closed over the ear-shaped inner
      capsule. As a result, the skin flap adopted an ear shape. The ear expander was
      left in place for 4 wk, removed with the help of a mini-incision, and stripped of
      its fibrous capsule. To simulate human ear reconstruction, the expander was
      replaced with an auriform silicone prosthesis, and the effects of auricular
      reconstruction were observed dynamically. RESULTS: All 12 skin flaps maintained
      abundant blood supply, created a clear outline of the ear framework, and produced
      a lifelike result. No complications were observed during the 4-wk observation
      period. CONCLUSIONS: The expanded skin flaps described here can mold to the
      desired contours and appear lifelike, as well as maintain abundant blood supply.
      This may provide a simpler approach to total ear reconstruction that reduces risk
      of complications.

PMID- 26303519
TI  - Reply: Prophylactic treatment of retinal breaks - a systematic review.

PMID- 26303520
TI  - [Bacteriologic investigation of the Eustachian tube and the implications of
      perioperative antibiotics before balloon dilation].
AB  - BACKGROUND: Balloon Eustachian Tuboplasty (BET) is a new minimally invasive
      treatment for chronic Eustachian tube dysfunction (ETD). Initially, perioperative
      prophylactic antibiotic therapy with ciprofloxacin 2 * 500 mg p.o. for 5 days was
      administered. This study aimed to characterize the bacterial flora in the ET,
      nose, and pharynx in patients with chronic obstructive ETD. Additionally, we
      investigated the necessity of perioperative antibiotic prophylaxis in BET
      patients. PATIENTS AND METHODS: We examined 40 patients undergoing BET: 20
      patients with and 20 patients without perioperative antibiotic prophylaxis. All
      patients were followed-up for clinical signs and symptoms of local infection for
      at least 2 weeks after surgery. Following BET, the tips of 35 balloon catheters,
      as well as swabs from the nose and pharynx were sent for microbiologic analysis.
      RESULTS: None of these 40 patients had postoperative signs of infection. Of the
      swabs of the balloon catheters, 46% were sterile and 23% showed standard flora.
      The remaining 31% of swaps revealed specific bacteria. However, none of the nasal
      or nasopharyngeal swaps were sterile. CONCLUSION: Due to the lack of signs of
      postoperative infection in either investigated group, the authors no longer favor
      use of perioperative antibiotic prophylaxis in patients undergoing BET. The
      relevance of biofilms and pathogen colonization to ET function has recently been
      intensively discussed, and should be further investigated in future studies.

PMID- 26303521
TI  - [The most important study results concerning nonsurgical primary treatment of
      locally advanced head and neck cancer: Highlights of the ASCO Meeting 2015].
AB  - At the Annual Meeting of the American Society of Clinical Oncology (ASCO) 2015,
      results of current trials dealing with nonsurgical primary treatment of locally
      advanced head and neck cancer were presented. Regarding concomitant
      chemoradiotherapy (CRT), studies focused on the dosage and sequence of cisplatin
      administration are currently particularly featured. Amongst these, a study on
      dosage reduction in human papilloma virus (HPV)-positive patients was presented.
      Other investigations addressed substances as alternatives for cisplatin,
      particularly carboplatin and targeted therapeutic agents. The comparison of
      concomitant and sequential CRT (induction chemotherapy (ICT) prior to CRT) is
      still one of the main topics. In addition, studies modifying the ICT regimen or
      combining subsequent radiotherapy (RT) with the epidermal growth factor receptor
      (EGFR) antibody cetuximab were presented. A selection of the most important
      trials are summarized in this article. 

PMID- 26303522
TI  - Dicyanovinyl-substituted J147 analogue inhibits oligomerization and fibrillation
      of beta-amyloid peptides and protects neuronal cells from beta-amyloid-induced
      cytotoxicity.
AB  - A series of novel J147 derivatives were synthesized, and their inhibitory
      activities against beta-amyloid (Abeta) aggregation and toxicity were evaluated
      by using the oligomer-specific antibody assay, the thioflavin-T fluorescence
      assay, and a cell viability assay in the transformed SH-SY5Y cell culture. Among
      the synthesized J147 derivatives, 3j with a 2,2-dicyanovinyl substituent showed
      the most potent inhibitory activity against Abeta42 oligomerization (IC50 = 17.3
      MUM) and Abeta42 fibrillization (IC50 = 10.5 MUM), and disassembled the preformed
      Abeta42 fibrils with an EC50 of 10.2 MUM. Finally, we confirmed that 3j is also
      effective at preventing neurotoxicity induced by Abeta42-oligomers as well as
      Abeta42-fibrils.

PMID- 26303523
TI  - miR-195 plays a role in steroid resistance of ulcerative colitis by targeting
      Smad7.
AB  - An imbalance in pro- and anti-inflammation is an important mechanism of steroid
      resistance in UC (ulcerative colitis), and miRNAs may participate in this
      process. The present study aimed to explore whether miRNAs play a role in the
      steroid resistance of UC by regulating gene expression of the inflammation signal
      pathway. SS (steroid-sensitive) patients, SR (steroid-resistant) patients and
      healthy individuals were recruited. In vivo miRNA profiles of serum samples
      showed that miR-195 was decreased significantly in the SR group compared with the
      SS group (P<0.05). This result was confirmed by qPCR (quantitative real-time PCR)
      and miRNA ISH (in situ hybridization) in serum and colon tissue samples. Online
      software was used to identify Smad7 mRNA as a potential target of miR-195. The
      direct interaction of miR-195 and Smad7 mRNA was investigated using a
      biotinylated miR-195 pull-down assay. Overexpression of a miR-195 precursor
      lowered cellular levels of Smad7 protein; conversely, antagonism of miR-195
      enhanced Smad7 translation without disturbing Smad7 mRNA levels. A luciferase
      reporter assay revealed a repressive effect of miR-195 via a single Smad7 3'-UTR
      target site, and point mutation of this site prevented miR-195-induced repression
      of Smad7 translation. Furthermore, increased levels of miR-195 led to a decrease
      in c-Jun and p65 expression. In contrast, transfection with anti-miR-195 led to
      increased levels of c-Jun and p65 protein. The decrease in miR-195 led to an
      increase in Smad7 expression and corresponding up-regulation of p65 and the AP-1
      (activator protein 1) pathway, which might explain the mechanism of steroid
      resistance in UC patients.

PMID- 26303524
TI  - Establishment of a recessive mutant small-eye rat with lens involution and
      retinal detachment associated with partial deletion and rearrangement of the
      Cryba1 gene.
AB  - From our stock of SDRs (Sprague-Dawley rats), we established a mutant strain
      having small opaque eyes and named it HiSER (Hirosaki small-eye rat). The HiSER
      phenotype is progressive and autosomal recessive. In HiSER eyes, disruption and
      involution of the lens, thickening of the inner nuclear layer, detachment and
      aggregation of the retina, rudimentary muscle in the ciliary body and cell
      infiltration in the vitreous humour were observed. Genetic linkage analysis using
      crossing with Brown Norway rat suggested that the causative gene(s) is located on
      chromosome 10. Microarray analysis showed that the expression level of the Cryba1
      gene encoding betaA3/A1-crystallin on chromosome 10 was markedly decreased in
      HiSER eyes. Genomic PCR revealed deletion of a 3.6-kb DNA region encompassing
      exons 4-6 of the gene in HiSERs. In HiSER eyes, a chimaeric transcript of the
      gene containing exons 1-3 and an approximately 250-bp sequence originating from
      the 3'-UTR of the Nufip2 gene, located downstream of the breakpoint in the
      opposite direction, was present. Whereas the chimaeric transcript was expressed
      in HiSER eyes, neither normal nor chimaeric betaA3/A1-crystallin proteins were
      detected by Western blot analysis. Real-time RT (reverse transcription)-PCR
      analysis revealed that expression level of the Nufip2 gene in the HiSER eye was
      40% of that in the SDR eye. These results suggest that the disappearance of the
      betaA3/A1-crystallin protein and, in addition, down-regulation of the Nufip2 gene
      as a consequence of gene rearrangement causes the HiSER phenotype. 

PMID- 26303525
TI  - Antibody-based exosite inhibitors of ADAMTS-5 (aggrecanase-2).
AB  - Adamalysin-like metalloproteinases with thrombospondin (TS) motifs (ADAMTS)-5 is
      the multi-domain metalloproteinase that most potently degrades aggrecan
      proteoglycan in the cartilage and its activity is implicated in the development
      of osteoarthritis (OA). To generate specific exosite inhibitors for it, we
      screened a phage display antibody library in the presence of the zinc-chelating
      active site-directed inhibitor GM6001 (Ilomastat) and isolated four highly
      selective inhibitory antibodies. Two antibodies were mapped to react with
      exosites in the catalytic/disintegrin domains (Cat/Dis) of the enzyme, one in the
      TS domain and one in the spacer domain (Sp). The antibody reacting with the Sp
      blocked the enzyme action only when aggrecan or the Escherichia coli-expressed
      aggrecan core protein were substrates, but not against a peptide substrate. The
      study with this antibody revealed the importance of the Sp for effective
      aggrecanolytic activity of ADAMTS-5 and that this domain does not interact with
      sulfated glycosaminoglycans (GAGs) but with the protein moiety of the
      proteoglycan. An antibody directed against the Cat/Dis of ADAMTS-5 was effective
      in a cell-based model of aggrecan degradation; however, the anti-Sp antibody was
      ineffective. Western blot analysis of endogenous ADAMTS-5 expressed by human
      chondrocytes showed the presence largely of truncated forms of ADAMTS-5, thus
      explaining the lack of efficacy of the anti-Sp antibody. The possibility of
      ADAMTS-5 truncation must then be taken into account when considering developing
      anti-ancillary domain antibodies for therapeutic purposes. 

PMID- 26303526
TI  - Recruitment of RAG1 and RAG2 to Chromatinized DNA during V(D)J Recombination.
AB  - V(D)J recombination is initiated by the binding of the RAG1 and RAG2 proteins to
      recombination signal sequences (RSSs) that consist of conserved heptamer and
      nonamer sequences separated by a spacer of either 12 or 23 bp. Here, we used RAG
      inducible pro-B v-Abl cell lines in conjunction with chromatin
      immunoprecipitation to better understand the protein and RSS requirements for RAG
      recruitment to chromatin. Using a catalytic mutant form of RAG1 to prevent
      recombination, we did not observe cooperation between RAG1 and RAG2 in their
      recruitment to endogenous Jkappa gene segments over a 48-h time course. Using
      retroviral recombination substrates, we found that RAG1 was recruited
      inefficiently to substrates lacking an RSS or containing a single RSS, better to
      substrates with two 12-bp RSSs (12RSSs) or two 23-bp RSSs (23RSSs), and more
      efficiently to a substrate with a 12/23RSS pair. RSS mutagenesis demonstrated a
      major role for the nonamer element in RAG1 binding, and correspondingly, a
      cryptic RSS consisting of a repeat of CA dinucleotides, which poorly re-creates
      the nonamer, was ineffective in recruiting RAG1. Our findings suggest that 12RSS
      23RSS cooperation (the "12/23 rule") is important not only for regulating RAG
      mediated DNA cleavage but also for the efficiency of RAG recruitment to
      chromatin. 

PMID- 26303527
TI  - The Set3 Complex Antagonizes the MYST Acetyltransferase Esa1 in the DNA Damage
      Response.
AB  - Acetylation is a dynamic posttranslational modification that contributes to
      chromatin-regulated processes, including DNA replication, repair, recombination,
      and gene expression. Acetylation is controlled by complexes containing opposing
      lysine and histone acetyltransferase (KAT and HAT) and deacetylase (KDAC and
      HDAC) activities. The essential MYST family Esa1 KAT acetylates core histones and
      many nonhistone substrates. Phenotypes of esa1 mutants include transcriptional
      silencing and activation defects, impaired growth at high temperatures, and
      sensitivity to DNA damage. The KDAC Rpd3 was previously identified as an activity
      opposing Esa1, as its deletion suppresses growth and silencing defects of esa1
      mutants. However, loss of Rpd3 does not suppress esa1 DNA damage sensitivity. In
      this work, we identified Hos2 as a KDAC counteracting ESA1 in the damage
      response. Deletion of HOS2 resulted in changes of esa1's transcriptional response
      upon damage. Further, loss of HOS2 or components of the Set3 complex (Set3C) in
      which it acts specifically suppressed damage sensitivity and restored esa1
      histone H4 acetylation. This rescue was mediated via loss of either Set3C
      integrity or of its binding to dimethylated histone H3K4. Our results thus add
      new insight into the interactions of an essential MYST acetyltransferase with
      diverse deacetylases to respond specifically to environmental and physiological
      challenges. 

PMID- 26303529
TI  - Mutagenesis of ARS2 Domains To Assess Possible Roles in Cell Cycle Progression
      and MicroRNA and Replication-Dependent Histone mRNA Biogenesis.
AB  - ARS2 is a regulator of RNA polymerase II transcript processing through its role
      in the maturation of distinct nuclear cap-binding complex (CBC)-controlled RNA
      families. In this study, we examined ARS2 domain function in transcript
      processing. Structural modeling based on the plant ARS2 orthologue, SERRATE,
      revealed 2 previously uncharacterized domains in mammalian ARS2: an N-terminal
      domain of unknown function (DUF3546), which is also present in SERRATE, and an
      RNA recognition motif (RRM) that is present in metazoan ARS2 but not in plants.
      Both the DUF3546 and zinc finger domain (ZnF) were required for association with
      microRNA and replication-dependent histone mRNA. Mutations in the ZnF disrupted
      interaction with FLASH, a key component in histone pre-mRNA processing. Mutations
      targeting the Mid domain implicated it in DROSHA interaction and microRNA
      biogenesis. The unstructured C terminus was required for interaction with the CBC
      protein CBP20, while the RRM was required for cell cycle progression and for
      binding to FLASH. Together, our results support a bridging model in which ARS2
      plays a central role in RNA recognition and processing through multiple protein
      and RNA interactions. 

PMID- 26303528
TI  - The DEK Oncoprotein Is a Critical Component of the EKLF/KLF1 Enhancer in
      Erythroid Cells.
AB  - Understanding how transcriptional regulators are themselves controlled is
      important in attaining a complete picture of the intracellular effects that
      follow signaling cascades during early development and cell-restricted
      differentiation. We have addressed this issue by focusing on the regulation of
      EKLF/KLF1, a zinc finger transcription factor that plays a necessary role in the
      global regulation of erythroid gene expression. Using biochemical affinity
      purification, we have identified the DEK oncoprotein as a critical factor that
      interacts with an essential upstream enhancer element of the EKLF promoter and
      exerts a positive effect on EKLF levels. This element also binds a core set of
      erythroid transcription factors, suggesting that DEK is part of a tissue
      restricted enhanceosome that contains BMP4-dependent and -independent components.
      Together with local enrichment of properly coded histones and an open chromatin
      domain, optimal transcriptional activation of the EKLF locus can be established. 

PMID- 26303530
TI  - Group IVA Cytosolic Phospholipase A2 Regulates the G2-to-M Transition by
      Modulating the Activity of Tumor Suppressor SIRT2.
AB  - The G2-to-M transition (or prophase) checkpoint of the cell cycle is a critical
      regulator of mitotic entry. SIRT2, a tumor suppressor gene, contributes to the
      control of this checkpoint by blocking mitotic entry under cellular stress.
      However, the mechanism underlying both SIRT2 activation and regulation of the G2
      to-M transition remains largely unknown. Here, we report the formation of a
      multiprotein complex at the G2-to-M transition in vitro and in vivo. Group IVA
      cytosolic phospholipase A2 (cPLA2alpha) acts as a bridge in this complex to
      promote binding of SIRT2 to cyclin A-Cdk2. Cyclin A-Cdk2 then phosphorylates
      SIRT2 at Ser331. This phosphorylation reduces SIRT2 catalytic activity and its
      binding affinity to centrosomes and mitotic spindles, promoting G2-to-M
      transition. We show that the inhibitory effect of cPLA2alpha on SIRT2 activity
      impacts various cellular processes, including cellular levels of histone H4
      acetylated at K16 (Ac-H4K16) and Ac-alpha-tubulin. This regulatory effect of
      cPLA2alpha on SIRT2 defines a novel function of cPLA2alpha independent of its
      phospholipase activity and may have implications for the impact of SIRT2-related
      effects on tumorigenesis and age-related diseases. 

PMID- 26303533
TI  - Conflict resolution.

PMID- 26303531
TI  - Functional Requirements for Fab-7 Boundary Activity in the Bithorax Complex.
AB  - Chromatin boundaries are architectural elements that determine the three
      dimensional folding of the chromatin fiber and organize the chromosome into
      independent units of genetic activity. The Fab-7 boundary from the Drosophila
      bithorax complex (BX-C) is required for the parasegment-specific expression of
      the Abd-B gene. We have used a replacement strategy to identify sequences that
      are necessary and sufficient for Fab-7 boundary function in the BX-C. Fab-7
      boundary activity is known to depend on factors that are stage specific, and we
      describe a novel ~700-kDa complex, the late boundary complex (LBC), that binds to
      Fab-7 sequences that have insulator functions in late embryos and adults. We show
      that the LBC is enriched in nuclear extracts from late, but not early, embryos
      and that it contains three insulator proteins, GAF, Mod(mdg4), and E(y)2. Its DNA
      binding properties are unusual in that it requires a minimal sequence of >65 bp;
      however, other than a GAGA motif, the three Fab-7 LBC recognition elements
      display few sequence similarities. Finally, we show that mutations which abrogate
      LBC binding in vitro inactivate the Fab-7 boundary in the BX-C. 

PMID- 26303532
TI  - Evidence for Homodimerization of the c-Fos Transcription Factor in Live Cells
      Revealed by Fluorescence Microscopy and Computer Modeling.
AB  - The c-Fos and c-Jun transcription factors, members of the activator protein 1 (AP
      1) complex, form heterodimers and bind to DNA via a basic leucine zipper and
      regulate the cell cycle, apoptosis, differentiation, etc. Purified c-Jun leucine
      zipper fragments could also form stable homodimers, whereas c-Fos leucine zipper
      homodimers were found to be much less stable in earlier in vitro studies. The
      importance of c-Fos overexpression in tumors and the controversy in the
      literature concerning c-Fos homodimerization prompted us to investigate Fos
      homodimerization. Forster resonance energy transfer (FRET) and molecular
      brightness analysis of fluorescence correlation spectroscopy data from live HeLa
      cells transfected with fluorescent-protein-tagged c-Fos indicated that c-Fos
      formed homodimers. We developed a method to determine the absolute concentrations
      of transfected and endogenous c-Fos and c-Jun, which allowed us to determine
      dissociation constants of c-Fos homodimers (Kd = 6.7 +/- 1.7 MUM) and c-Fos-c-Jun
      heterodimers (on the order of 10 to 100 nM) from FRET titrations. Imaging
      fluorescence cross-correlation spectroscopy (SPIM-FCCS) and molecular dynamics
      modeling confirmed that c-Fos homodimers were stably associated and could bind to
      the chromatin. Our results establish c-Fos homodimers as a novel form of the AP-1
      complex that may be an autonomous transcription factor in c-Fos-overexpressing
      tissues and could contribute to tumor development. 

PMID- 26303534
TI  - Medical marijuana does not increase adolescent marijuana use.

PMID- 26303535
TI  - Intervention effect fades over time: when, how, and for whom?

PMID- 26303536
TI  - Bullying, victimisation, and psychosis.

PMID- 26303537
TI  - Psychopathology after foster care or institutional rearing.

PMID- 26303538
TI  - "As a parent, there is no rulebook": a new resource for parents and carers of
      young people who self-harm.

PMID- 26303539
TI  - Rethinking the biopsychosocial formulation.

PMID- 26303540
TI  - Rethinking cigarette smoking, cannabis use, and psychosis.

PMID- 26303541
TI  - Mental health and suicide risk in Northern Ireland: a legacy of the Troubles?

PMID- 26303542
TI  - Corrections. Pharmacological prevention of post-traumatic stress disorder and
      acute stress disorder: a systematic review and meta-analysis.

PMID- 26303543
TI  - The realm of auditory hallucinations.

PMID- 26303544
TI  - Cosmetic neurosurgery, ethics, and enhancement.

PMID- 26303545
TI  - Cosmetic neurosurgery, ethics, and enhancement - Author's reply.

PMID- 26303546
TI  - Medically unexplained symptom management.

PMID- 26303547
TI  - The land of the free.

PMID- 26303549
TI  - Cynthia Joyce.

PMID- 26303550
TI  - Conference report: 30th Annual Congress of the Association of Argentinian
      Psychiatrists.

PMID- 26303551
TI  - Wakley essay: Treading water.

PMID- 26303552
TI  - Trust-credibility is always at stake: Ann Liv Young's Sherapy at the World
      Psychiatric Association Congress.

PMID- 26303553
TI  - Model bodies.

PMID- 26303558
TI  - Effect of an early perinatal depression intervention on long-term child
      development outcomes: follow-up of the Thinking Healthy Programme randomised
      controlled trial.
AB  - BACKGROUND: Perinatal depression has been linked with deleterious child
      development outcomes, yet maternal depression interventions have not been shown
      to have lasting effects on child development, and evidence is not available from
      countries of low or middle income. In the Thinking Healthy Programme cluster
      randomised controlled trial, a perinatal depression intervention was assessed in
      Pakistan in 2006-07. The intervention significantly reduced depression levels 12
      months post partum compared with a control. We aimed to assess the effect of this
      same intervention on the cognitive, socioemotional, and physical development of
      children at around age 7 years. METHODS: Mother-child dyads who participated in
      the Thinking Healthy Programme cluster-randomised controlled trial were
      interviewed when the index child was about 7 years old. A reference group of 300
      mothers who did not have prenatal depression and, therefore, did not receive the
      original intervention, was enrolled with their children at the same time. The
      primary cognitive outcome was the score on the Wechsler Preschool and Primary
      Scale of Intelligence (WPPSI-IV); primary socioemotional outcomes included scores
      on the Strengths and Difficulties Questionnaire (SDQ) and the Spence Children's
      Anxiety Scale (SCAS); and primary physical outcomes were height-for-age, weight
      for-age, and body-mass index (BMI)-for-age Z scores. Generalised linear modelling
      with random effects to account for clustering was the main method of analysis.
      Analyses were by intention to treat. The Thinking Healthy Programme cluster
      randomised trial was registered at ISRCTN.com, number ISRCTN65316374. FINDINGS:
      Of 705 participating mother-child dyads interviewed at the end of the Thinking
      Healthy Programme randomised controlled trial, 584 (83%) dyads were enrolled. 289
      mothers had received the intervention and 295 had received a control consisting
      of enhanced usual care. The mean age of the children was 7.6 years (SD 0.1).
      Overall, cognitive, socioemotional, or physical development outcomes did not
      differ between children in the intervention or control groups whose mothers had
      prenatal depression. When compared with the reference group of children whose
      mothers did not have prenatal depression, the Thinking Healthy Programme trial
      children had worse socioemotional outcomes; mean scores were significantly higher
      on the SDQ for total difficulty (11.34 vs 10.35; mean difference 0.78, 95% CI
      0.09-1.47; p=0.03) and on the SCAS for anxiety (21.33 vs 17.57; mean difference
      2.93, 1.15-4.71; p=0.0013). Cognitive and physical outcomes did not differ.
      INTERPRETATION: Our findings show that cognitive, socioemotional, and physical
      developmental outcomes of children at age 7 years whose mother had prenatal
      depression did not differ between those who received the Thinking Healthy
      Programme intervention and those who received the control. Further investigation
      is needed to understand what types of complex interventions or approaches are
      needed for long-term gains in maternal and child wellbeing. Prolonged, detailed,
      and frequent follow-up is warranted for all interventions. FUNDING: Grand
      Challenges Canada (Government of Canada), Saving Brains programme.

PMID- 26303557
TI  - Medical marijuana laws and adolescent marijuana use in the USA from 1991 to 2014:
      results from annual, repeated cross-sectional surveys.
AB  - BACKGROUND: Adolescent use of marijuana is associated with adverse later effects,
      so the identification of factors underlying adolescent use is of substantial
      public health importance. The relationship between US state laws that permit
      marijuana for medical purposes and adolescent marijuana use has been
      controversial. Such laws could convey a message about marijuana acceptability
      that increases its use soon after passage, even if implementation is delayed or
      the law narrowly restricts its use. We used 24 years of national data from the
      USA to examine the relationship between state medical marijuana laws and
      adolescent use of marijuana. METHODS: Using a multistage, random-sampling design
      with replacement, the Monitoring the Future study conducts annual national
      surveys of 8th, 10th, and 12th-grade students (modal ages 13-14, 15-16, and 17-18
      years, respectively), in around 400 schools per year. Students complete self
      administered questionnaires that include questions on marijuana use. We analysed
      data from 1 098 270 adolescents surveyed between 1991 and 2014. The primary
      outcome of this analysis was any marijuana use in the previous 30 days. We used
      multilevel regression modelling with adolescents nested within states to examine
      two questions. The first was whether marijuana use was higher overall in states
      that ever passed a medical marijuana law up to 2014. The second was whether the
      risk of marijuana use changed after passage of medical marijuana laws. Control
      covariates included individual, school, and state-level characteristics.
      FINDINGS: Marijuana use was more prevalent in states that passed a medical
      marijuana law any time up to 2014 than in other states (adjusted prevalence
      15.87% vs 13.27%; adjusted odds ratio [OR] 1.27, 95% CI 1.07-1.51; p=0.0057).
      However, the risk of marijuana use in states before passing medical marijuana
      laws did not differ significantly from the risk after medical marijuana laws were
      passed (adjusted prevalence 16.25% vs 15.45%; adjusted OR 0.92, 95% CI 0.82-1.04;
      p=0.185). Results were generally robust across sensitivity analyses, including
      redefining marijuana use as any use in the previous year or frequency of use, and
      reanalysing medical marijuana laws for delayed effects or for variation in
      provisions for dispensaries. INTERPRETATION: Our findings, consistent with
      previous evidence, suggest that passage of state medical marijuana laws does not
      increase adolescent use of marijuana. However, overall, adolescent use is higher
      in states that ever passed such a law than in other states. State-level risk
      factors other than medical marijuana laws could contribute to both marijuana use
      and the passage of medical marijuana laws, and such factors warrant
      investigation. FUNDING: US National Institute on Drug Abuse, Columbia University
      Mailman School of Public Health, New York State Psychiatric Institute.

PMID- 26303559
TI  - Bullying victimisation and risk of psychotic phenomena: analyses of British
      national survey data.
AB  - BACKGROUND: Being bullied is an aversive experience with short-term and long-term
      consequences, and is incorporated in biopsychosocial models of psychosis. We used
      the 2000 and the 2007 British Adult Psychiatric Morbidity Surveys to test the
      hypothesis that bullying is associated with individual psychotic phenomena and
      with psychosis, and predicts the later emergence of persecutory ideation and
      hallucinations. METHODS: We analysed two nationally representative surveys of
      individuals aged 16 years or older in Great Britain (2000) and England (2007).
      Respondents were presented with a card listing stressful events to identify
      experiences of bullying over the entire lifespan. We assessed associations with
      the dependent variables persecutory ideation, auditory and visual hallucinations,
      and diagnosis of probable psychosis. All analyses were controlled for
      sociodemographic confounders, intelligence quotient (IQ), and other traumas.
      FINDINGS: We used data for 8580 respondents from 2000 and 7403 from 2007.
      Bullying was associated with presence of persecutory ideation and hallucinations,
      remaining so after adjustment for sociodemographic factors, IQ, other traumas,
      and childhood sexual abuse. Bullying was associated with a diagnosis of probable
      psychosis. If reported at baseline, bullying predicted emergence and maintenance
      of persecutory ideation and hallucinations during 18 months of follow-up in the
      2000 survey. Controlling for other traumas and childhood sexual abuse did not
      affect the association between bullying and psychotic symptoms, but reduced the
      significance of the association with diagnosis of probable psychosis. Bullying
      was most strongly associated with the presence of concurrent persecutory ideation
      and hallucinations. INTERPRETATION: Bullying victimisation increases the risk of
      individual psychotic symptoms and of a diagnosis of probable psychosis. Early
      detection of bullying and use of treatments oriented towards its psychological
      consequences might ameliorate the course of psychosis. FUNDING: None.

PMID- 26303560
TI  - Effects of institutional rearing and foster care on psychopathology at age 12
      years in Romania: follow-up of an open, randomised controlled trial.
AB  - BACKGROUND: Early social deprivation can negatively affect domains of
      functioning. We examined psychopathology at age 12 years in a cohort of Romanian
      children who had been abandoned at birth and placed into institutional care, then
      assigned either to be placed in foster care or to care as usual. METHODS: We used
      follow-up data from the Bucharest Early Intervention Project (BEIP), a randomised
      controlled trial of abandoned children in all six institutions for young children
      in Bucharest, Romania. In the initial trial, 136 children, enrolled between ages
      6-31 months, were randomly assigned to either care as usual or placement in
      foster care. In this study we followed up these children at age 12 years to
      assess psychiatric symptoms using the Diagnostic Interview Schedule for Children
      (4th edition; DISC-IV). We also recruited Romanian children who had never been
      placed in an institution from paediatric clinics and schools in Bucharest as a
      comparator group who had never been placed in an institution. The primary outcome
      measure was symptom counts assessed through DISC-IV scores for three domains of
      psychopathology: internalising symptoms, externalising symptoms, and attention
      deficit hyperactivity disorder (ADHD). We compared mean DISC-IV scores between
      trial participants and comparators who had never been placed in an institution,
      and those assigned to care as usual or foster care. Analyses were done by
      modified intention to treat. This trial is registered with ClinicalTrials.gov,
      number NCT00747396. FINDINGS: We followed up 110 children from the BEIP trial
      between Jan 27, 2011, and April 11, 2014, and 49 children as comparators who had
      never been placed in an institution. The 110 children who had ever been placed in
      an institution had higher symptom counts for internalising disorders (mean 0.93
      [SD 1.68] vs 0.45 [0.84], difference 0.48 [95% CI 0.14-0.82]; p=0.0127),
      externalising disorders (2.31 [2.86] vs 0.65 [1.33], difference 1.66 [1.06-2.25];
      p<0.0001), and ADHD (4.00 [5.01] vs 0.71 [1.85], difference 3.29 [95% CI 2.39
      4.18]; p<0.0001) than did children who had never been placed in an institution.
      Compared with 55 children randomly assigned to receive care as usual, the 55
      children in the foster-care group had fewer externalising symptoms (mean 2.89 [SD
      3.00] for care as usual vs 1.73 [2.61] for foster care, difference 1.16 [95% CI
      0.11 to 2.22]; p=0.0255), but symptom counts for internalising disorders (mean
      1.00 [1.59] for care as usual vs 0.85 [1.78] for foster care, difference 0.15 [
      0.35 to 0.65]; p=0.5681) and ADHD (mean 3.76 [4.61] for care as usual vs 4.24
      [5.41] for foster care, difference -0.47 [-2.15 to 1.20; p=0.5790) did not
      differ. In further analyses, symptom scores substantially differed by stability
      of foster-care placement. INTERPRETATION: Early foster care slightly reduced the
      risk of psychopathology in children who had been living in institutions, but long
      term stability of foster-care placements is an important predictor of
      psychopathology in early adolescence. FUNDING: National Institute of Mental
      Health and the John D and Catherine T MacArthur Foundation.

PMID- 26303561
TI  - Patient-reported depression measures in cancer: a meta-review.
AB  - The patient-reported depression measures that perform best in oncology settings
      have not yet been identified. We did a meta-review to integrate the findings of
      reviews of more than 50 depression measures used in adults with, or recovering
      from, any type of cancer. We searched Medline, PsycINFO, Embase, and grey
      literature from 1999 to 2014 to identify 19 reviews representing 372 primary
      studies. 11 reviews were rated as being of high quality (defined as meeting at
      least 20 criteria in the Preferred Reporting Items for Systematic Reviews and
      Meta-Analyses statement). The Hospital Anxiety Depression Scale (HADS) was the
      most thoroughly evaluated measure, but was limited by cutpoint variability. The
      HADS had moderate screening utility indices and was least recommended in advanced
      cancer or palliative care. The Beck Depression Inventory was more generalisable
      across cancer types and disease stages, with good indices for screening and case
      finding. The Center for Epidemiologic Studies Depression Scale was the best
      weighted measure in terms of responsiveness. This meta-review provides a
      comprehensive overview of the strengths and limitations of available depression
      measures. It can inform the choice of the best measure for specific settings and
      purposes. 

PMID- 26303562
TI  - Psychodynamic therapy meets evidence-based medicine: a systematic review using
      updated criteria.
AB  - Psychodynamic therapy (PDT) is an umbrella concept for treatments that operate on
      an interpretive-supportive continuum and is frequently used in clinical practice.
      The use of any form of psychotherapy should be supported by sufficient evidence.
      Efficacy research has been neglected in PDT for a long time. In this review, we
      describe methodological requirements for proofs of efficacy and summarise the
      evidence for use of PDT to treat mental health disorders. After specifying the
      requirements for superiority, non-inferiority, and equivalence trials, we did a
      systematic search using the following criteria: randomised controlled trial of
      PDT; use of treatment manuals or manual-like guidelines; use of reliable and
      valid measures for diagnosis and outcome; adults treated for specific mental
      problems. We identified 64 randomised controlled trials that provide evidence for
      the efficacy of PDT in common mental health disorders. Studies sufficiently
      powered to test for equivalence to established treatments did not find
      substantial differences in efficacy. These results were corroborated by several
      meta-analyses that suggest PDT is as efficacious as treatments established in
      efficacy. More randomised controlled trials are needed for some mental health
      disorders such as obsessive-compulsive disorder and post-traumatic stress
      disorder. Furthermore, more adequately powered equivalence trials are needed. 

PMID- 26303563
TI  - Childhood: a suitable case for treatment?
AB  - We examine the contemporary debate on attention deficit hyperactivity disorder,
      in which concerns about medicalisation and overuse of drug treatments are
      paramount. We show medicalisation in attention deficit hyperactivity disorder to
      be a complex issue that requires systematic research to be properly understood.
      In particular, we suggest that the debate on this disorder might be more
      productive and less divisive if longitudinal, evidence-based understanding of the
      harms and benefits of psychiatric diagnosis and misdiagnosis existed, as well as
      better access to effective, non-drug treatments. If articulation of the values
      that should guide clinical practice in child psychiatry is encouraged, this might
      create greater trust and less division. 

PMID- 26303564
TI  - Food and your mood: nutritional psychiatry.

PMID- 26303566
TI  - Diabetes and depression: does worsening control of diabetes lead to poorer
      depression outcomes?
AB  - RATIONALE, AIMS AND OBJECTIVES: The relationship between diabetes and depression
      is complex. The aim of this study was to study the impact of diabetic control in
      depressed primary care patients with diabetes on clinical remission of their
      depression at 6 months. METHODS: This study was a retrospective chart review
      analysis of 145 adult patients diagnosed with either major depressive disorder or
      dysthymia and had a score of 10 or greater on the PHQ-9. The dependent variable
      for this study was depression remission at 6 months. The independent variables
      for this study were age, gender, marital status, race, BMI and HbA1c level within
      2 months prior to the time of depression diagnosis. RESULTS: Multiple logistic
      regression modelling demonstrated that initial diabetic control or obesity were
      not independent predictors of depression remission at 6 months after index date.
      Also, the odds for the diabetes being in control (HbA1c <8.0%) after 6 months was
      only associated with being in control at baseline (OR 5.549, CI 2.364-13.024, P <
      0.001). CONCLUSIONS: Baseline diabetic control does not appear to be an
      independent predictor for depression outcomes at 6 months. The best predictor of
      diabetic control after the diagnosis of depression was previous control of
      diabetes.

PMID- 26303567
TI  - Description of Streptomyces fabae sp. nov., a producer of antibiotics against
      microbial pathogens, isolated from soybean (Glycine max) rhizosphere soil.
AB  - An actinomycete, designated strain T66T and isolated from soybean rhizosphere
      soil at Gyeonggi Siheung Sorae in the Republic of Korea, has antibiotic activity
      against a broad range of microbial pathogens. The strain was determined to be
      closely related to several known species in the genus Streptomyces on the basis
      of 16S rRNA gene sequence data (97.73-98.07 % similarity). The strain exhibited
      cell-wall chemotype I and phospholipid type II. The menaquinones present were MK
      9 (H6), MK-9 (H8) and MK-10 (H2). Major fatty acids were anteiso-C15 : 0, iso-C16
      : 0, iso-C15 : 0, and anteiso-C17 : 0. The level of DNA-DNA relatedness between
      strain T66T and closely related type strains was determined to be below 40 %.
      Strain T66T had spiral spore chains and a rugose spore surface that is different
      from its closest relatives. Comparison of the genotypic and phenotypic features
      confirmed that strain T66T ( = KEMB 9005-219T = KACC 18226T = NBRC 110902T)
      should be considered as the type strain of a novel species in the genus
      Streptomyces, for which the name Streptomyces fabae sp. nov. is proposed.

PMID- 26303568
TI  - The daily incidence of out-of-hospital cardiac arrest unexpectedly increases
      around New Year's Day in Japan.
AB  - BACKGROUND: Over 100,000 patients are diagnosed every year as out-of-hospital
      cardiac arrest (OHCA) cases in Japan and their number has continued to rise for
      the last decade, presenting a challenge for preventive public health research as
      well as emergency medical care. The purpose of this study was to identify whether
      there are any temporal patterns in daily OHCA presentations in Japan. METHODS:
      Records of OHCA patients (n=701,651) transported by ambulance over the course of
      six years (1st January 2005 to 10th March 2011) in Japan were obtained from the
      All-Japan Utstein registry data of cardiopulmonary arrest patients. Time periods
      within which the incidence of OHCA significantly increased were identified by a
      temporal cluster detection test using scan statistics. The risk ratios of OHCA
      for the detected periods were calculated and adjusted according to a Poisson
      regression model accounting for effects of other factors. RESULTS: The risk of
      OHCA significantly rises 1.3-1.6 times around New Year's Day in Japan.
      CONCLUSIONS: Our analysis revealed the increased daily incidence of OHCA around
      every New Year's Day in Japan.

PMID- 26303569
TI  - Mechanical chest compression does not seem to improve outcome after out-of
      hospital cardiac arrest. A single center observational trial.
AB  - AIM: Recently three large post product placement studies, comparing mechanical
      chest compression (cc) devices to those who received manual cc, found equivalent
      outcome results for both groups. Thus the question arises whether those results
      could be replicated using the devices on a daily routine. METHODS: We
      prospectively enrolled 948 patients over a 12 months period. Chi-Square test and
      Mann-Whitney-U test were used to assess differences between "manual" and
      "mechanical" cc subgroups. Uni- and multivariate Cox regression hazard analysis
      were used to assess the influence of cc type on survival. RESULTS: A mechanical
      cc device was used in 30.1% (n=283) cases. Patients who received mechanical cc
      had a significantly worse neurological outcome - measured in cerebral performance
      category (CPC) - than the manual cc group (56.8% vs. 78.6%, p=0.009). Patients
      receiving mechanical cc were significantly younger, more were male and were more
      likely to have bystander CPR and an initially shock-able ECG rhythm. There was no
      difference in the quality of CPR that might explain the worse outcome in
      mechanical cc patients. CONCLUSION: Even with high quality CPR in both, manual
      and mechanical cc groups, outcome in patients who received mechanical cc was
      significantly worse. The anticipated benefits of a higher compression ratio and a
      steadier compression depth of a mechanical cc device remain uncertain. In this
      study selection for mechanical cc was not standardized, and was non-random. This
      merits further investigation. Further research on how mechanical cc is chosen and
      used should be considered. CLINICAL TRIAL REGISTRATION:
      https://ekmeduniwien.at/core/catalog/2013/ (EK-Nr:1221/2013).

PMID- 26303570
TI  - Survival and neurocognitive outcomes in pediatric extracorporeal-cardiopulmonary
      resuscitation.
AB  - OBJECTIVE: Extracorporeal Cardiopulmonary Resuscitation (E-CPR) is the initiation
      of extracorporeal life support during active chest compressions. There are no
      studies describing detailed neurocognitive outcomes of this population. We aim to
      describe the survival and neurocognitive outcomes of children who received E-CPR.
      METHODS: Prospective cohort study. Children who received E-CPR at the Stollery
      Children's Hospital between 2000 and 2010 were included. Neurocognitive follow
      up, including Wechsler Preschool and Primary Scales of Intelligence, was
      completed at the age of 4.5 years, and at a minimum of 6 months after the E-CPR
      admission. RESULTS: Fifty-five patients received E-CPR between 2000 and 2010.
      Children with cardiac disease had a 49% survival to hospital discharge and 43%
      survival at age 5-years, with no survivors (n=4) in those with non-cardiac
      disease. Pediatric E-CPR survivors had a mean (SD) Full Scale Intelligence
      quotient (FSIQ) score of 76.5 (15.9); with 4 children (24%) having intellectual
      disability (defined as FSIQ over 2 standard deviations below the population mean;
      i.e., <70). Multiple Cox regression analysis found that mechanical ventilation
      prior to E-CPR, open chest CPR, longer duration of CPR, low pH and more red blood
      cells given on the first day of ECMO, and longer time for lactate to normalize on
      ECMO were associated with higher mortality at age 5-years. CONCLUSION: Pediatric
      patients with cardiac disease who required E-CPR had 43% survival at age 5 years.
      Of concern, the intelligence quotient in E-CPR survivors was significantly lower
      than the population mean, with 24% having intellectual disability.

PMID- 26303571
TI  - Advanced life support provider course in Italy: A 5-year nationwide study to
      identify the determinants of course success.
AB  - INTRODUCTION: The advanced life support (ALS) provider course is the gold
      standard for teaching and assessing competence in advanced resuscitation.
      Outcomes over a 5-year period of European Resuscitation (ERC)/IRC ALS provider
      courses in Italy were investigated, and the factors associated with course
      success are described. METHODS: In 2008, the Italian Resuscitation Council (IRC)
      created a database in which every ERC/IRC ALS course was recorded. Data from
      courses organized from 2008 to 2012 were analysed. The data included: candidate's
      age and degree (medical doctor (MD) or nurse), medical specialty of MD
      candidates, course outcomes, duration and reference guidelines, number of
      instructors and course director. Relationships between the course outcomes and
      the courses and candidates' characteristics were analysed using logistic
      regression. RESULTS: A total of 13,624 candidates were evaluated from 871
      courses. Among the candidates, 55% were MDs and 45% were nurses. Ninety-seven
      percent of candidates passed the final evaluation, while 3% failed. Candidates
      who passed were younger (37 [31-44] vs. 43 [37-50] years, p<0.0001) and had a
      greater pre-course resuscitation knowledge (multiple choice quiz (MCQ) score: 88
      [83-93] vs. 80 [73-87], p<0.0001) compared to those who failed. The course pass
      rate was higher for MDs compared to nurses (98% vs. 95%, p<0.0001) and
      participants in emergency disciplines were most significantly associated with
      course success (chi(2) 71, p<0.0001). In the multivariate analysis, an older age
      (OR 0.926, 95%CI [0.915-0.937]) was independently associated with course failure,
      while being a MD (OR 3.021, 95%CI [2.212-4.132]), having a higher pre-course MCQ
      score (OR 1.033, 95%CI [1.026-1.040]) together with a higher candidate/instructor
      ratio (OR 1.314, 95%CI [1.067-1.618]), and having a longer course duration (OR
      1.717, 95%CI [1.090-2.703]), were independently associated with success.
      CONCLUSIONS: Younger age, professional background, and pre-course resuscitation
      knowledge are the most important predictors of ALS provider course success,
      together with higher candidate/instructor ratios and longer course durations.

PMID- 26303572
TI  - Outcome of out-of-hospital cardiac arrest over a period of 15 years in comparison
      to the RACA score in a physician staffed urban emergency medical service in
      Germany.
AB  - BACKGROUND: Patient outcome after out of hospital cardiac arrest (OHCA) depends
      on the cardiopulmonary resuscitation (CPR) performance and might also be
      influenced by organisation of the emergency medical service (EMS) and
      implementation of guidelines. AIM: To assess the rate of return of spontaneous
      circulation (ROSC) after cardiac arrest to the predicted rate by the ROSC after
      cardiac arrest (RACA) score over a 15-year period reflecting three different
      implemented ALS-guidelines in a physician-staffed EMS. METHODS: All adult
      patients with non-traumatic OHCA in the EMS of Bonn from 1996 to 2011 were
      included. Utstein data from three 5-years time periods (1996-2001, 2001-2006,
      2006-2011) representing different ALS-guideline implementations were collected.
      Group comparisons were made in terms of incidence, epidemiology and short-term
      outcome of CPR with emphasis on changes over time and factors of importance. In
      each group observed ROSC rate were compared to the predicted ROSC rates (the RACA
      score). RESULTS: CPR by the ALS unit was attempted in a total of 1989 patients
      (735, 666, and 588 patients in the first, second and third period, respectively).
      Average crude incidence of CPR per 100,000 person-years decreased over time
      (61.3; 55.5; 49.0/100,000/years) while patients treated were significantly older
      (65.5 +/- 16.5; 67.9 +/- 15; 68.9 +/- 15.7 (p<0.001)). Observed ROSC rates were
      higher than predicted by the RACA score in all time periods, however, admittance
      to ICU decreased significantly from 50% in the first five-year period to 38% last
      five-year period (p<0.001). From first to third period the proportion of arrests
      with first observed rhythm of VT/VF arrests did not change (29% vs. 27%, p=0.323)
      nor there were changes in bystander CPR rates (17% vs. 17%, p=0.520).
      CONCLUSIONS: In a 15-years period and in the setting of a physician-staffed EMS
      the ROSC rates remain higher than predicted by the RACA score but the admittance
      to the ICU after OHCA declined significantly. This finding was accompanied by a
      decrease in CPR incidence and an increase in age of patients.

PMID- 26303574
TI  - Magnitude and associated factors of Atopic dermatitis among children in Ayder
      referral hospital, Mekelle, Ethiopia.
AB  - BACKGROUND: Atopic Dermatitis (AD) is now a day's increasing in prevalence
      globally. A Prevalence of 5-25 % have been reported in different country. Even if
      its prevalence is known in most countries especially in developing countries
      there is scarcity with regard to prevalence and associated risk factors of AD
      among children in Ethiopia settings. The aim of this study was to determine the
      magnitude and associated factors of atopic dermatitis among children in Ayder
      referral hospital, Mekelle, Ethiopia. METHODS: A facility-based cross-sectional
      study design was conducted among 477 children aged from 3 months to 14 years in
      Ayder referral hospital from July to September, 2014. A systematic random
      sampling technique was used to identify study subjects. Descriptive analysis was
      done to characterize the study population. Bivariate and multivariate logistic
      regression was used to identify factors associated with AD. The OR with 95 % CI
      was used to show the strength of the association and a P value < 0.05 was used to
      declare the cut of point in determining the level of significance. RESULTS: Among
      the total respondents, 237 (50.4 %) were males and 233 (49.6 %) were females. The
      magnitude of the atopic dermatitis was found to be 9.6 % (95 % CI: 7.2, 12.5). In
      multivariate logistic regression model, those who had maternal asthma (AOR: 11.5,
      95 % CI:3.3-40.5), maternal hay fever history (AOR: 23.5, 95 % CI: 4.6-118.9) and
      atopic dermatitis history (AOR: 6.0, 95 % CI:1.0-35.6), Paternal asthma (AOR:
      14.4, 95 % CI:4.0-51.7), Paternal hay fever history (AOR: 13.8, 95 % CI: 2.4
      78.9) and personal asthma (AOR: 10.5, 95 % CI:1.3-85.6), and hay fever history
      (AOR: 12.9, 95 % CI:2.7-63.4), age at 3 months to 1 year (OR: 6.8, 95 % CI: 1.1
      46.0) and weaning at 4 to 6 months age (AOR: 3.9, 95 % CI:1.2-13.3) were a
      significant predictors of atopic dermatitis. CONCLUSION: In this study the
      magnitude of atopic dermatitis was high in relation to other studies conducted so
      far in the country. Maternal, paternal, personal asthma, hay fever histories,
      maternal atopic dermatitis history, age of child and age of weaning were
      independent predicators of atopic dermatitis. Hence, the finding alert a needs of
      strengthening the national skin diseases prevention and control services in
      particular in skin care of children related to atopic dermatitis and others. In
      avoiding early initiation of supplementary feeding specially with personal and
      families with atopic problem needs further attention of prevention activities.

PMID- 26303575
TI  - The Role of Values in Attitudes towards Violence: Discrimination against
      Moroccans and Romanian Gypsies in Spain.
AB  - The first objective of this study was to investigate whether police violence is
      more tolerated when the victim is a member of a social minority (e.g., Moroccan
      immigrants and Romanian Gypsies in Spain) than when the victim is a member of the
      social majority (e.g., Spaniards). The second objective was to use Schwartz value
      theory to examine the moderating role of values on attitudes towards tolerance of
      police violence. The participants were 207 sociology and social work students
      from a public university in Madrid. Overall, in this study, police violence was
      more accepted when the victim was a member of a social minority; F(2, 206) =
      77.91, p = .001, etap 2 = 0.433, and in general, values moderated this
      acceptance. Thus, greater adherence to the conservation and self-promotion values
      subsystems would strengthen support for police violence towards a social minority
      member. On the other hand, greater adherence to the openness to change and self
      transcendence subsystems diminish this support. 

PMID- 26303573
TI  - Suppressed invasive and migratory behaviors of SW1353 chondrosarcoma cells
      through the regulation of Src, Rac1 GTPase, and MMP13.
AB  - Chondrosarcoma is the second frequent type of primary bone cancer. In response to
      stress to the endoplasmic reticulum, activation of eIF2alpha-mediated signaling
      is reported to induce apoptosis. However, its effects on invasive and migratory
      behaviors of chondrosarcoma have not been understood. Focusing on potential roles
      of Src kinase, Rac1 GTPase, and MMP13, we investigated eIF2alpha-driven
      regulation of SW1353 chondrosarcoma cells. In particular, we employed two
      chemical agents (salubrinal, Sal; and guanabenz, Gu) that elevate the level of
      eIF2alpha phosphorylation. The result revealed that both Sal and Gu reduced
      invasion and motility of SW1353 chondrosarcoma cells in a dose dependent manner.
      Live imaging using a fluorescent resonance energy transfer (FRET) technique
      showed that Sal and Gu downregulated activities of Src kinase as well as Rac1
      GTPase in an eIF2alpha dependent manner. RNA interference experiments supported
      an eIF2alpha-mediated regulatory network in the inhibitory role of Sal and Gu.
      Partial silencing of MMP13 also suppressed malignant phenotypes of SW1353
      chondrosarcoma cells. However, MMP13 was not regulated via eIF2alpha since
      administration of Sal but not Gu reduced expression of MMP13. In summary, we
      demonstrate that eIF2alpha dependent and independent pathways regulate invasion
      and motility of SW1353 chondrosarcoma cells, and inactivation of Src, Rac1, and
      MMP13 by Sal could provide a potential adjuvant therapy for combating metastatic
      chondrosarcoma cells. 

PMID- 26303576
TI  - Dual-functionalized poly(amidoamine) dendrimers with poly(ethylene glycol)
      conjugation and thiolation improved blood compatibility.
AB  - OBJECTIVES: This study aims to examine the blood compatibility of dual
      functionalized poly(amidoamine) (PAMAM) dendrimers. METHODS: The cationic PAMAM
      dendrimer of generation 4.0 (PM4.0) were functionalized by poly(ethylene glycol)
      (PEG) conjugation or by thiolation or the combination of both methods. Various in
      vitro assays including immune cell cytotoxicity, haemoglobin release, serum
      albumin binding, complement activation and coagulation times were used to
      characterize the compatibility with blood components. KEY FINDINGS: Although
      thiolation of polymers has been reported as a strategy to reduce platelet
      activation or aggregation, thiolation of PM4.0 alone did not offer any protective
      effect against the dendrimer toxicity on blood components or functions.
      PEGylation was able to reduce the toxic effect and interactions of the unmodified
      and thiolated PM4.0 on various blood components and functions; yet, PEGylated
      PM4.0 displayed prolonged prothrombin times and activated partial thromboplastin
      times. Among various PM4.0 derivatives, dual-functionalized PM4.0 with PEG and
      thiol groups displayed the least toxicity to various blood components and
      functions. CONCLUSIONS: Our findings suggested that comprehensive studies of
      dendrimer biocompatibility should be performed so as to establish the safe dose
      window for systemic administration.

PMID- 26303577
TI  - Impact of conflict and displacement on risk behaviours amongst people who inject
      drugs in Kabul, Afghanistan.

PMID- 26303578
TI  - Molecular mechanism of dietary phospholipid requirement of Atlantic salmon, Salmo
      salar, fry.
AB  - The phospholipid (PL) requirement in fish is revealed by enhanced performance
      when larvae are provided PL-enriched diets. To elucidate the molecular mechanism
      underlying PL requirement in Atlantic salmon, Salmo salar, were fed a minimal PL
      diet and tissue samples from major lipid metabolic sites were dissected from fry
      and parr. In silico analysis and cloning techniques demonstrated that salmon
      possess a full set of enzymes for the endogenous production of PL. The gene
      expression data indicated that major PL biosynthetic genes of phosphatidylcholine
      (PtdCho), phosphatidylethanolamine (PtdEtn) and phosphatidylinositol (PtdIns)
      display lower expression in intestine during the early developmental stage (fry).
      This is consistent with the hypothesis that the intestine of salmon is immature
      at the early developmental stage with limited capacity for endogenous PL
      biosynthesis. The results also indicate that intact PtdCho, PtdEtn and PtdIns are
      required in the diet at this stage. PtdCho and sphingomyelin constitute the
      predominant PL in chylomicrons, involved in the transport of dietary lipids from
      the intestine to the rest of the body. As sphingomyelin can be produced from
      PtdCho in intestine of fry, our findings suggest that supplementation of dietary
      PtdCho alone during early developmental stages of Atlantic salmon would be
      sufficient to promote chylomicron formation. This would support efficient
      transport of dietary lipids, including PL precursors, from the intestine to the
      liver where biosynthesis of PtdEtn, PtdSer, and PtdIns is not compromised as in
      intestine facilitating efficient utilisation of dietary energy and the endogenous
      production of membrane PL for the rapidly growing and developing animal. 

PMID- 26303579
TI  - Sodium Citrate Inhibits Endoplasmic Reticulum Stress in Rats with Adenine-Induced
      Chronic Renal Failure.
AB  - BACKGROUND/AIMS: Endoplasmic reticulum stress (ERS) is an important self
      protective cellular response to harmful stimuli that contribute to various
      diseases, including chronic renal failure (CRF). Sodium citrate plays an
      important role in antioxidant and cellular immunity, but whether it improves ERS
      in CRF is unclear. METHODS: The rats were randomly divided into five groups: the
      control group, the sodium citrate control group, the model group, model rats with
      low dose sodium citrate (216 mg/kg), and model rats with a high dose of sodium
      citrate (746 mg/kg). The rats were euthanized at 6, 8, 12, and 16 weeks with
      their blood and renal tissue in detection. RESULTS: The increased concentrations
      of blood urea nitrogen and serum creatinine in the model group were significantly
      decreased by sodium citrate treatment. Hematoxylin-eosin and Masson staining
      showed that sodium citrate treatment apparently improved renal pathological
      changes in CRF rats. Western blot analysis showed that sodium citrate treatment
      decreased the protein levels of transforming growth factor-beta 1 and collagen
      type IV, which were increased in model rats. Moreover, immunohistochemical
      staining demonstrated that sodium citrate could effectively reduce the protein
      expression of glucose-regulated protein 78 kDa and CCAAT/enhancer-binding protein
      homologous protein in the model rats, which was consistent with western blot
      results. Additionally, the high dose of sodium citrate had a stronger protective
      effect in CRF rats than the low dose of sodium citrate. CONCLUSIONS: Sodium
      citrate has a protective effect on CRF through its effects on ERS.

PMID- 26303581
TI  - Prompt access to effective malaria treatment among children under five in sub
      Saharan Africa: a multi-country analysis of national household survey data.
AB  - BACKGROUND: Scaling up diagnostic testing and treatment is a key strategy to
      reduce the burden of malaria. Delays in accessing treatment can have fatal
      consequences; however, few studies have systematically assessed these delays
      among children under five years of age in malaria-endemic countries of sub
      Saharan Africa. This study identifies predictors of prompt treatment with first
      line artemisinin combination therapy (ACT) and describes profiles of children who
      received this recommended treatment. METHODS: This study uses data from the most
      recent Demographic and Health Survey, Malaria Indicator Survey, or Anaemia and
      Parasite Prevalence Survey conducted in 13 countries. A Chi square automatic
      interaction detector (CHAID) model was used to identify factors associated with
      prompt and effective treatment among children under five years of age. RESULTS:
      The percentage of children with fever who received any anti-malarial treatment
      varies from 3.6 % (95 % CI 2.8-4.4 %) in Ethiopia to 64.5 % (95 % CI 62.7-66.2 %)
      in Uganda. Among those who received prompt treatment with any anti-malarial
      medicine, the percentage who received ACT ranged from 32.2 % (95 % CI 26.1-38.4
      %) in Zambia to nearly 100 % in Tanzania mainland and Zanzibar. The CHAID
      analysis revealed that country of residence is the best predictor of prompt and
      effective treatment (p < 0.001). Depending on the country, the second best
      predictor was maternal education (p = 0.004), place of residence (p = 0.008), or
      household wealth index (p < 0.001). CONCLUSIONS: This study reveals that country
      of residence, maternal education, place of residence, and socio-economic status
      are key predictors of prompt access to malaria treatment. Achieving universal
      coverage and the elimination agenda will require effective monitoring to detect
      disparities early and sustained investments in routine data collection and policy
      formulation.

PMID- 26303582
TI  - Multifractal analysis of tumour microscopic images in the prediction of breast
      cancer chemotherapy response.
AB  - Due to the individual heterogeneity, highly accurate predictors of chemotherapy
      response in invasive breast cancer are needed for effective chemotherapeutic
      management. However, predictive molecular determinants for conventional
      chemotherapy are only emerging and still incorporate a high degree of predictive
      variability. Based on such pressing need for predictive performance improvement,
      we explored the value of pre-therapy tumour histology image analysis to predict
      chemotherapy response. Fractal analysis was applied to hematoxylin/eosin stained
      archival tissue of diagnostic biopsies derived from 106 patients diagnosed with
      invasive breast cancer. The tissue was obtained prior to neoadjuvant
      anthracycline-based chemotherapy and patients were subsequently divided into
      three groups according to their actual chemotherapy response: partial
      pathological response (pPR), pathological complete response (pCR) and
      progressive/stable disease (PD/SD). It was shown that multifractal analysis of
      breast tumour tissue prior to chemotherapy indeed has the capacity to distinguish
      between histological images of the different chemotherapy responder groups with
      accuracies of 91.4% for pPR, 82.9% for pCR and 82.1% for PD/SD. F(alpha)max was
      identified as the most important predictive parameter. It represents the maximum
      of multifractal spectrum f(alpha), where alpha is the Holder's exponent. This is
      the first study investigating the predictive value of multifractal analysis as a
      simple and cost-effective tool to predict the chemotherapy response. Improvements
      in chemotherapy prediction provide clinical benefit by enabling more optimal
      chemotherapy decisions, thus directly affecting the quality of life and survival.

PMID- 26303583
TI  - Recording axonal conduction to evaluate the integration of pluripotent cell
      derived neurons into a neuronal network.
AB  - Stem cell transplantation is a promising therapy to treat neurodegenerative
      disorders, and a number of in vitro models have been developed for studying
      interactions between grafted neurons and the host neuronal network to promote
      drug discovery. However, methods capable of evaluating the process by which stem
      cells integrate into the host neuronal network are lacking. In this study, we
      applied an axonal conduction-based analysis to a co-culture study of primary and
      differentiated neurons. Mouse cortical neurons and neuronal cells differentiated
      from P19 embryonal carcinoma cells, a model for early neural differentiation of
      pluripotent stem cells, were co-cultured in a microfabricated device. The somata
      of these cells were separated by the co-culture device, but their axons were able
      to elongate through microtunnels and then form synaptic contacts. Propagating
      action potentials were recorded from these axons by microelectrodes embedded at
      the bottom of the microtunnels and sorted into clusters representing individual
      axons. While the number of axons of cortical neurons increased until 14 days in
      vitro and then decreased, those of P19 neurons increased throughout the culture
      period. Network burst analysis showed that P19 neurons participated in
      approximately 80% of the bursting activity after 14 days in vitro. Interestingly,
      the axonal conduction delay of P19 neurons was significantly greater than that of
      cortical neurons, suggesting that there are some physiological differences in
      their axons. These results suggest that our method is feasible to evaluate the
      process by which stem cell-derived neurons integrate into a host neuronal
      network.

PMID- 26303580
TI  - Cerebellar BOLD signal during the acquisition of a new lexicon predicts its early
      consolidation.
AB  - Cerebellar contributions to language are presently poorly understood, but it has
      been argued that the cerebellar role in motor learning can be extended to
      learning in cognitive and linguistic domains. Here, we used fMRI to investigate
      whether the cerebellum is recruited in mapping novel words onto existing semantic
      concepts. On separate days, participants performed a Basque vocabulary learning
      task and a control English synonym task in the MRI scanner. Learning-related BOLD
      activity was found in left inferior frontal gyrus, bilateral insula, pre-SMA,
      left superior parietal cortex, right caudate, the right cerebellar vermis and
      right cerebellar Crus II. The extent to which the cerebellar regions, but not the
      cerebral areas, were recruited during learning correlated positively with
      participants' off-line improvement in performance after the learning task. These
      data provide evidence for a cerebellar role in lexical learning, and suggest that
      the right cerebellum may contribute toward consolidation of lexico-semantic
      associations in the language network.

PMID- 26303584
TI  - NSCLC without Antineoplastic Treatment: Incidence, Characteristics, and Outcome
      as Outlined in the TYROL Study.
AB  - BACKGROUND: The treatment of non-small cell lung cancer (NSCLC) has become more
      and more individualized with the availability of potent and less toxic therapies.
      However, there are still patients who do not receive antineoplastic treatment.
      The aim of this study was to investigate the incidence of 'no treatment', its
      reasons, and the outcome of untreated NSCLC patients in recent years. PATIENTS
      AND METHODS: Medical files of 1,256 consecutive NSCLC patients diagnosed between
      2001 and 2009 at the Medical University of Innsbruck and affiliated hospitals
      were retrospectively analyzed. RESULTS: In 66 of the 1,256 patients (5.3%), the
      absence of antineoplastic treatment could be ascertained. The median age was 72.1
      years, and 42 patients (63.3%) were males. The majority of patients presented
      with stage IV (n=45; 68.2%). Treatment was omitted due to physical deterioration
      in 41 patients (62.1%), and 25 patients (37.9%) refused any treatment. The median
      overall survival of the untreated patients was 3.1 months (refusal: 9.7 months;
      physical deterioration: 2.1 months). CONCLUSION: This study provides information
      on the incidence of NSCLC patients without antineoplastic treatment and gives a
      detailed description of the characteristics and comorbidities. These data might
      help clinicians in the survival estimations of their NSCLC patients in scenarios
      like therapy refusal or poor physical condition.

PMID- 26303585
TI  - Examining progress in cancer rehabilitation: are we closer to parity of esteem?

PMID- 26303586
TI  - The Worcestershire Prostate Cancer Survivorship Programme: patient needs at a
      community-based centre.

PMID- 26303587
TI  - The Prostate Cancer Survivorship Care Assessment Tool: development of a new way
      to assess survivorship care quality.

PMID- 26303589
TI  - Symptomatic Secondary Polycythemia Induced by Anti-VEGF Therapy for the Treatment
      of Metastatic Renal Cell Carcinoma: A Case Series and Review.

PMID- 26303588
TI  - Coevolutionary analyses require phylogenetically deep alignments and better null
      models to accurately detect inter-protein contacts within and between species.
AB  - BACKGROUND: When biomolecules physically interact, natural selection operates on
      them jointly. Contacting positions in protein and RNA structures exhibit
      correlated patterns of sequence evolution due to constraints imposed by the
      interaction, and molecular arms races can develop between interacting proteins in
      pathogens and their hosts. To evaluate how well methods developed to detect
      coevolving residues within proteins can be adapted for cross-species, inter
      protein analysis, we used statistical criteria to quantify the performance of
      these methods in detecting inter-protein residues within 8 angstroms of each
      other in the co-crystal structures of 33 bacterial protein interactions. We also
      evaluated their performance for detecting known residues at the interface of a
      host-virus protein complex with a partially solved structure. RESULTS: Our
      quantitative benchmarking showed that all coevolutionary methods clearly benefit
      from alignments with many sequences. Methods that aim to detect direct
      correlations generally outperform other approaches. However, faster mutual
      information based methods are occasionally competitive in small alignments and
      with relaxed false positive rates. Two commonly used null distributions are anti
      conservative and have high false positive rates in some scenarios, although the
      empirical distribution of scores performs reasonably well with deep alignments.
      CONCLUSIONS: We conclude that coevolutionary analysis of cross-species protein
      interactions holds great promise but requires sequencing many more species pairs.

PMID- 26303590
TI  - Global Quality of Life After Curative Treatment for Prostate Cancer: What
      Matters? A Study Among Members of the Norwegian Prostate Cancer Patient
      Association.
AB  - INTRODUCTION: The purpose of this study was to identify factors that are
      associated with quality of life (QoL) in relapse-free patients after radical
      prostatectomy or high-dose radiotherapy with or without hormone treatment.
      PATIENTS AND METHODS: A cross-sectional postal survey among members of the
      Norwegian Prostate Cancer Patient Association was used. We analyzed associations
      between QoL and general health, "typical" adverse effects (sexual, urinary, and
      bowel assessed using the Expanded Prostate Cancer Composite items) and
      psychosocial variables (work ability, family life, social life and/or leisure
      activities) in univariate and multivariate regression analyses. Statistical
      significance was defined as P < .01. RESULTS: Among 612 responders (approximately
      50% compliance; median age, 70 years), in univariate analyses QoL was
      significantly associated with functional aspects and the level of bother within
      the sexual, urinary, and bowel domains and with general health and psychosocial
      aspects of daily life. In the multivariate analysis only general health and
      social life and/or leisure activities remained associated with QoL, with work
      ability being a third factor in patients younger than 65 years old. Posttreatment
      worsening of partnership was reported by 12% of the patients. CONCLUSION:
      Prostate cancer patients who are to undergo curative treatment should be informed
      about the risk of reduced function within the sexual, urinary, and bowel domains,
      but also about these dysfunctions' relation to bother and QoL, considered
      together with the patients' general health and their preferences as to their
      social life activities.

PMID- 26303591
TI  - Meta-analysis of studies with bivariate binary outcomes: a marginal beta-binomial
      model approach.
AB  - When conducting a meta-analysis of studies with bivariate binary outcomes,
      challenges arise when the within-study correlation and between-study
      heterogeneity should be taken into account. In this paper, we propose a marginal
      beta-binomial model for the meta-analysis of studies with binary outcomes. This
      model is based on the composite likelihood approach and has several attractive
      features compared with the existing models such as bivariate generalized linear
      mixed model (Chu and Cole, 2006) and Sarmanov beta-binomial model (Chen et al.,
      2012). The advantages of the proposed marginal model include modeling the
      probabilities in the original scale, not requiring any transformation of
      probabilities or any link function, having closed-form expression of likelihood
      function, and no constraints on the correlation parameter. More importantly,
      because the marginal beta-binomial model is only based on the marginal
      distributions, it does not suffer from potential misspecification of the joint
      distribution of bivariate study-specific probabilities. Such misspecification is
      difficult to detect and can lead to biased inference using currents methods. We
      compare the performance of the marginal beta-binomial model with the bivariate
      generalized linear mixed model and the Sarmanov beta-binomial model by simulation
      studies. Interestingly, the results show that the marginal beta-binomial model
      performs better than the Sarmanov beta-binomial model, whether or not the true
      model is Sarmanov beta-binomial, and the marginal beta-binomial model is more
      robust than the bivariate generalized linear mixed model under model
      misspecifications. Two meta-analyses of diagnostic accuracy studies and a meta
      analysis of case-control studies are conducted for illustration.

PMID- 26303592
TI  - A self-reporting tetrazole-based linker for the biofunctionalization of gold
      nanorods.
AB  - A photochemical approach based on nitrile imine-mediated tetrazole-ene
      cycloaddition is introduced to functionalize gold nanorods with biomolecules. For
      this purpose, a bifunctional, photoreactive linker containing thioctic acid as
      the Au anchoring group and a tetrazole moiety for the light-induced reaction with
      maleimide-capped DNA was prepared. The tetrazole-based reaction on the
      nanoparticles' surface results in a fluorescent pyrazoline product allowing for
      the spectroscopic monitoring of the reaction. This first example of nitrile imine
      mediated tetrazole-ene cycloaddition (NITEC)-mediated biofunctionalization of Au
      nanorods paves the way for the attachment of sensitive biomolecules, such as
      antibodies and other proteins, under mild conditions and expands the toolbox for
      the tailoring of nanomaterials. 

PMID- 26303594
TI  - Decade in review-bone: Great strides made but still further to go.

PMID- 26303593
TI  - Overlap in Eating Disorders and Obesity in Adolescence.
AB  - While eating disorders and obesity have traditionally been conceptualized as
      separate conditions, recent research suggests important overlap in several areas
      including etiology, comorbidity, risk factors, and prevention approaches.
      Examining the commonality among these conditions is particularly important as
      adolescents who present with both eating disorder symptomology and obesity
      demonstrate poorer outcomes within weight control treatments and are at greater
      risk for future development of full threshold eating disorders and additional
      weight gain. The purpose of this paper is to review the research examining the
      overlap in prevalence rates for eating disorders and obesity in adolescents, as
      well as shared etiology, risk factors, and psychiatric and medical comorbidities.
      Current preventive and treatment approaches also will be discussed, while
      highlighting the need for more integrated assessment, prevention, and treatment
      efforts that focus on maladaptive eating and activity patterns shared by both
      eating disorders and obesity. 

PMID- 26303598
TI  - Adrenal gland: Aldosterone-producing mutations in normal adrenal glands.

PMID- 26303599
TI  - Decade in review-type 2 diabetes mellitus: At the centre of things.

PMID- 26303602
TI  - Nutrition: All calories are not equal--cutting dietary fat is more effective than
      cutting carbohydrates.

PMID- 26303600
TI  - PTH receptor-1 signalling-mechanistic insights and therapeutic prospects.
AB  - Parathyroid hormone/parathyroid hormone-related protein receptor (PTH/PTHrP type
      1 receptor; commonly known as PTHR1) is a family B G-protein-coupled receptor
      (GPCR) that regulates skeletal development, bone turnover and mineral ion
      homeostasis. PTHR1 transduces stimuli from PTH and PTHrP into the interior of
      target cells to promote diverse biochemical responses. Evaluation of the
      signalling properties of structurally modified PTHR1 ligands has helped to
      elucidate determinants of receptor function and mechanisms of downstream cellular
      and physiological responses. Analysis of PTHR1 responses induced by structurally
      modified ligands suggests that PTHR1 can continue to signal through a G-protein
      mediated pathway within endosomes. Such findings challenge the longstanding
      paradigm in GPCR biology that the receptor is transiently activated at the cell
      membrane, followed by rapid deactivation and receptor internalization. Evaluation
      of structurally modified PTHR1 ligands has further led to the identification of
      ligand analogues that differ from PTH or PTHrP in the type, strength and duration
      of responses induced at the receptor, cellular and organism levels. These
      modified ligands, and the biochemical principles revealed through their use,
      might facilitate an improved understanding of PTHR1 function in vivo and enable
      the treatment of disorders resulting from defects in PTHR1 signalling. This
      Review discusses current understanding of PTHR1 modes of action and how these
      findings might be applied in future therapeutic agents. 

PMID- 26303601
TI  - Acylcarnitines--old actors auditioning for new roles in metabolic physiology.
AB  - Perturbations in metabolic pathways can cause substantial increases in plasma and
      tissue concentrations of long-chain acylcarnitines (LCACs). For example, the
      levels of LCACs and other acylcarnitines rise in the blood and muscle during
      exercise, as changes in tissue pools of acyl-coenzyme A reflect accelerated fuel
      flux that is incompletely coupled to mitochondrial energy demand and capacity of
      the tricarboxylic acid cycle. This natural ebb and flow of acylcarnitine
      generation and accumulation contrasts with that of inherited fatty acid oxidation
      disorders (FAODs), cardiac ischaemia or type 2 diabetes mellitus. These
      conditions are characterized by very high (FAODs, ischaemia) or modestly
      increased (type 2 diabetes mellitus) tissue and blood levels of LCACs. Although
      specific plasma concentrations of LCACs and chain-lengths are widely used as
      diagnostic markers of FAODs, research into the potential effects of excessive
      LCAC accumulation or the roles of acylcarnitines as physiological modulators of
      cell metabolism is lacking. Nevertheless, a growing body of evidence has
      highlighted possible effects of LCACs on disparate aspects of pathophysiology,
      such as cardiac ischaemia outcomes, insulin sensitivity and inflammation. This
      Review, therefore, aims to provide a theoretical framework for the potential
      consequences of tissue build-up of LCACs among individuals with metabolic
      disorders.

PMID- 26303603
TI  - Trial Watch: Antisenses working overtime in lipids.

PMID- 26303604
TI  - Effectiveness of a new dietetic weight management food to achieve weight loss in
      client-owned obese cats.
AB  - OBJECTIVES: The aim of the study was to evaluate weight loss and maintenance
      parameters in cats fed a novel weight management food and to assess the owner's
      perception of the cat's quality of life. METHODS: This study was designed as a
      prospective, uncontrolled/unmasked clinical trial. One hundred and thirty-two
      overweight/obese, otherwise healthy, client-owned cats were enrolled. Initial
      evaluation included physical examination, nutritional assessment, ideal body
      weight determination and weight-loss feeding guidelines development. Follow-up
      evaluations (monthly for 6 months) encompassed determination of body weight, body
      condition score, body fat index, muscle condition score and feeding practices.
      Quality of life assessment by owners included the cat's level of energy,
      happiness, appetite, begging behavior, flatulence, stool volume and fecal score.
      RESULTS: Eighty-three percent of the cats lost weight, with an average +/- SEM
      weight loss of 11.0 +/- 1.8% over 6 months and an average +/- SE weekly weight
      loss rate of 0.45 +/- 0.02%. The mean +/- SEM duration of weight loss was 134.0
      +/- 4.8 days. Fourteen percent of cats achieved an ideal body weight. Seventy
      nine percent of cats ate more calories from novel weight management food than the
      recommended daily energy requirement for weight loss, and the majority of these
      cats still lost weight. Body condition score and body fat index decreased over
      time compared with baseline from weeks 12-24 and from weeks 8-24, respectively.
      Owners perceived an increase in energy and happiness (>week 12) in the cats that
      lost weight, without changes in appetite or begging behavior. CONCLUSIONS AND
      RELEVANCE: This study confirmed the effectiveness of the novel weight management
      food in achieving weight loss in overweight/obese client-owned cats. Owners
      reported significant improvements in their cat's quality of life without negative
      side effects.

PMID- 26303605
TI  - Emphysematous pyelonephritis in a domestic shorthair cat.
AB  - A 3-year-old male castrated domestic shorthair cat was presented with an acute
      history of lethargy and decreased appetite. Pertinent physical examination
      abnormalities included palpable irregularity of the right kidney and pain on
      palpation of the left kidney. Ultrasonographic imaging of the abdomen revealed
      gas present at the corticomedullary junction of the left kidney, consistent with
      emphysematous pyelonephritis, as well as emphysematous cystitis. While
      quantitative urine culture via pyelocentesis yielded a negative culture, a sample
      via cystocentesis was positive for Escherichia coli and emphysematous changes
      were presumed most likely secondary to an ascending infection. The purpose of
      this report is to describe the temporary management of ureteral obstruction
      secondary to emphysematous pyelonephritis using a ureteral stent in a cat.

PMID- 26303606
TI  - Changes in the response to excitatory antagonists, agonists, and spasmolytic
      agents in circular colonic smooth muscle strips from patients with
      diverticulosis.
AB  - BACKGROUND: Colonic samples from asymptomatic diverticulosis (DS) patients
      presented enhanced electrical field stimulation (EFS)-contractions, in an earlier
      study of ours, suggesting increased endogenous responses. The aim of this study
      was to explore changes in excitatory neuromuscular transmission and to assess the
      pharmacodynamics of spasmolytic agents in DS. METHODS: Circular muscle strips
      from sigmoid colon of DS patients (n = 30; 69.5 +/- 14.8 years) and controls (n =
      32; 64.7 +/- 16.2 years) were studied using organ baths to evaluate the direct
      effect of excitatory agonists (carbachol, neurokinin A [NKA] and substance P
      [SP]), and the effect of antagonists (atropine and NK2 antagonist GR94800) and
      spasmolytic drugs (otilonium bromide [OB] and N-butyl-hyoscine) on the
      contractions induced by EFS-stimulation of excitatory motorneurons. qRT-PCR was
      also performed to compare mRNA expression of M2 , M3 , NK2 receptors and L-type
      calcium channels. KEY RESULTS: Contractions to carbachol (Emax : 663.7 +/- 305.6%
      control vs 2698.0 +/- 439.5% DS; p < 0.0005) and NKA (Emax : 387.8 +/- 35.6% vs
      1102.0 +/- 190.1%; p < 0.0005) were higher in DS group, without differences for
      SP. Higher potency for DS patients was observed in the concentration-response
      curves for atropine (pIC50  = 8.56 +/- 0.15 control vs pIC50  = 9.95 +/- 0.18 DS
      group; p < 0.005) and slightly higher for GR94800 (pIC50  = 7.21 +/- 0.18 control
      vs pIC50  = 7.97 +/- 0.32 group; p < 0.0001). Lower efficacy (Emax ) and potency
      (pIC50 ) was observed for spasmolytic drugs in DS, whereas no differences were
      found regarding the relative expression of the receptors evaluated between
      groups. CONCLUSIONS & INFERENCES: The greater response to cholinergic and
      tachykinergic agonists and greater potency for muscarinic and NK2 antagonists
      observed in DS might play a role in the spasticity found in diverticular disease.

PMID- 26303607
TI  - News on Clinical Details and Treatment in PGM1-CDG.
AB  - Phosphoglucomutase 1 deficiency has recently been reported as a novel disease
      that belongs to two different classes of metabolic disorders, congenital
      disorders of glycosylation (CDG) and glycogen storage diseases.This paper focuses
      on previously reported siblings with short stature, hypothyroidism, increased
      transaminases, and, in one of them, dilated cardiomyopathy (DCM). An intronic
      point mutation in the PGM1-gene (c.1145-222 G>T) leads to a complex alternative
      splicing pattern and to almost complete absence of PGM1 activity.Exercise-induced
      muscle fatigue, chest pain, and rhabdomyolysis persisted into adulthood. Fainting
      occurred during the first minutes of strong exercise due to glucose depletion and
      serum heart troponin was increased. A second wind phenomenon with an improvement
      in exercise capacity after some minutes of training was observed. Regular aerobic
      training improved fitness and helped to avoid acute damage. DCM improved during
      therapy.Glycosylation deficiency was most prominent in childhood. Glycosylation
      improved with age and further improved with oral galactose supplementation even
      in adulthood. Optimal improvement of glycosylation-dependent phenotypes should be
      achieved by early and permanent galactose treatment.However, in case of mutations
      in ZASP, DCM can develop as a consequence of impaired binding of PGM1 to the
      heart-specific isoform of ZASP, independently of overall glycosylation
      efficiency. Thus, even if mutations in PGM1 impair the function of the ZASP-PGM1
      complex, supplementation of galactose cannot be expected to restore that
      function. Therefore, knowledge of PGM1 deficiency in a patient should prompt
      surveillance of early signs of DCM and specific treatment if necessary. 

PMID- 26303608
TI  - Normal Neurodevelopmental Outcomes in PNPO Deficiency: A Case Series and
      Literature Review.
AB  - Pyridox(am)ine 5'-phosphate oxidase deficiency results in an early-onset neonatal
      encephalopathy that can be fatal if not detected and treated early. The condition
      is rare, can result in preterm delivery, and can mimic hypoxic ischemic
      encephalopathy. Thus, suspicion of the diagnosis, appropriate investigations, and
      therapeutic trials with pyridoxal-5'-phosphate are often delayed. In this paper
      we report four cases of pyridox(am)ine 5'-phosphate oxidase deficiency, two of
      whom are siblings. Three were treated with pyridoxal-5'-phosphate in the first
      few days of life and the fourth within the first month. One of the siblings was
      electively treated from birth until a diagnosis was secured. Our cases
      demonstrate that early diagnosis and treatment can be associated with normal
      neurodevelopment in childhood. We suggest that a low threshold for investigating
      for pyridox(am)ine 5'-phosphate oxidase deficiency and electively treating with
      pyridoxal-5'-phosphate is considered in any neonate with encephalopathy,
      including those with presumed hypoxic ischemic encephalopathy in whom the degree
      of encephalopathy is not expected from perinatal history, cord gases and/or
      neuroimaging. 

PMID- 26303609
TI  - Reduction of Plasma Globotriaosylsphingosine Levels After Switching from
      Agalsidase Alfa to Agalsidase Beta as Enzyme Replacement Therapy for Fabry
      Disease.
AB  - INTRODUCTION: Agalsidase alfa and agalsidase beta, recombinant enzyme
      preparations for treatment of Fabry disease (FD), have different approved dosing
      schedules: 0.2 mg/kg and 1.0 mg/kg every other week (EOW), respectively. METHODS:
      This open-label, multicenter, exploratory phase 4 study evaluated plasma
      globotriaosylsphingosine (lyso-GL-3) and plasma and urine globotriaosylceramide
      (GL-3) levels at baseline and 2, 4, and 6 months after the switch from agalsidase
      alfa (0.2 mg/kg EOW for >=12 months) to agalsidase beta (1.0 mg/kg EOW) in 15
      male patients with FD. Immunoglobulin (Ig)G antidrug antibody titers were
      assessed, and safety was monitored throughout the study. RESULTS: Plasma lyso-GL
      3 concentrations decreased significantly within 2 months after switch and
      reductions continued through month 6 (mean absolute changes, -12.8, -16.1, and 
      16.7 ng/mL at 2, 4, and 6 months, respectively; all P < 0.001). The mean
      percentage reduction from baseline was 39.5% (P < 0.001) at month 6. For plasma
      GL-3, the mean absolute change from baseline (-0.9 MUg/mL) and percentage
      reduction (17.9%) at month 6 were both significant (P < 0.05). Urine GL-3
      measurements showed intra-patient variability and changes from baseline were not
      significant. No clinical outcomes were assessed in this 6-month study, and,
      therefore, no conclusions can be drawn regarding the correlation of observed
      reductions in glycosphingolipid concentrations with clinically relevant outcomes.
      There were no differences in IgG antidrug antibody titers between the two
      enzymes. The switch from agalsidase alfa to agalsidase beta was well tolerated.
      CONCLUSION: Plasma lyso-GL-3 and GL-3 levels reduced after switching from
      agalsidase alfa to agalsidase beta, indicating that agalsidase beta has a greater
      pharmacodynamic effect on these markers at the recommended dose. These data
      further support the use of agalsidase beta 1.0 mg/kg EOW as enzyme replacement
      therapy in FD.

PMID- 26303610
TI  - Mucopolysaccharidosis (MPS) Physical Symptom Score: Development, Reliability, and
      Validity.
AB  - OBJECTIVES: We quantified medical signs and symptoms to construct the Physical
      Symptom Score (PSS) for use in research to assess somatic disease burden in
      mucopolysaccharidoses (MPS) to track disease and monitor treatments. We examined
      scoring reliability, its concurrent validity with other measures, and
      relationship to age in MPS type I. METHODS: Fifty-four patients with MPS I (36
      with Hurler syndrome treated with hematopoietic cell transplant and 18 with
      attenuated MPS I treated with enzyme replacement therapy), ages 5 to 18 years,
      were seen longitudinally over 5 years. The summation of frequency and severity of
      signs of specific organ involvement, surgeries, and hydrocephalus drawn from
      medical histories comprise the PSS. We examined relationship to age and to daily
      living skills (DLS) from the Vineland Adaptive Behavior Scale and physical
      quality of life from the Child Health Questionnaire (CHQ) for each group.
      RESULTS: The PSS was associated with age in both groups, indicating increase in
      disease burden over time. The PSS was significantly negatively associated with
      DLS (r = -0.48) and CHQ (r = -0.55) in the attenuated MPS I but not in the Hurler
      group. CONCLUSIONS: The association of somatic disease burden with physical
      quality of life and ability to carry out daily living skills suggests that the
      PSS will be useful in the measurement of disease and treatment effects in the
      attenuated MPS I group. Earlier treatment with transplant and differing parental
      expectations are possible explanations for its lack of association with other
      outcomes necessitating an adaptation for Hurler syndrome in the future.

PMID- 26303611
TI  - Infantile Refsum Disease: Influence of Dietary Treatment on Plasma Phytanic Acid
      Levels.
AB  - Infantile Refsum disease (IRD) is one of the less severe of Zellweger spectrum
      disorders (ZSDs), a group of peroxisomal biogenesis disorders resulting from a
      generalized peroxisomal function impairment. Increased plasma levels of very long
      chain fatty acids (VLCFA) and phytanic acid are biomarkers used in IRD diagnosis.
      Furthermore, an increased plasma level of phytanic acid is known to be associated
      with neurologic damage. Treatment of IRD is symptomatic and multidisciplinary.The
      authors report a 3-year-old child, born from consanguineous parents, who
      presented with developmental delay, retinitis pigmentosa, sensorineural deafness
      and craniofacial dysmorphisms. While the relative level of plasma C26:0 was
      slightly increased, other VLCFA were normal. Thus, a detailed characterization of
      the phenotype was essential to point to a ZSD. Repeatedly increased levels of
      plasma VLCFA, along with phytanic acid and pristanic acid, deficient
      dihydroxyacetone phosphate acyltransferase activity in fibroblasts and
      identification of the homozygous pathogenic mutation c.2528G>A (p.Gly843Asp) in
      the PEX1 gene, confirmed this diagnosis. Nutritional advice and follow-up was
      proposed aiming phytanic acid dietary intake reduction. During dietary treatment,
      plasma levels of phytanic acid decreased to normal, and the patient's development
      evaluation showed slow progressive acquisition of new competences.This case
      report highlights the relevance of considering a ZSD in any child with
      developmental delay who manifests hearing and visual impairment and of performing
      a systematic biochemical investigation, when plasma VLCFA are mildly increased.
      During dietary intervention, a biochemical improvement was observed, and the long
      term clinical effect of this approach needs to be evaluated. 

PMID- 26303612
TI  - Safety and Efficacy of Chronic Extended Release Cornstarch Therapy for Glycogen
      Storage Disease Type I.
AB  - BACKGROUND: Glycogen storage disease type I (GSD I) causes severe hypoglycemia
      during periods of fasting since both glycogenolysis and gluconeogenesis are
      impaired. Primary treatment in North America consists of cornstarch therapy every
      3-4 h. Waxy maize extended release cornstarch was introduced for maintaining
      overnight glucose concentrations, but no studies have assessed long-term safety
      and efficacy of the product. OBJECTIVE: To demonstrate the safety and efficacy of
      modified cornstarch in GSD I. DESIGN: An open-label overnight trial of extended
      release cornstarch was performed. Subjects with a successful trial (optimal
      metabolic control 2 or more hours longer than with traditional cornstarch) were
      given the option of continuing into the chronic observational phase. Subjects
      were assessed biochemically at baseline and after 12 months. RESULTS: Of the 106
      subjects (93 GSD Ia/13 GSD Ib), efficacy was demonstrated in 82 patients (88%)
      with GSD Ia and 10 patients (77%) with GSD Ib. The success rate for extending
      fasting was 95% for females and 78% for males. Of the patients who entered the
      longitudinal phase, long-term data are available for 44 subjects. Mean duration
      of fasting on traditional cornstarch prior to study for the cohort was 4.1 and
      7.8 h on the extended release cornstarch (P < 0.001). All laboratory markers of
      metabolic control have remained stable in the chronically treated patients.
      CONCLUSION: Extended release cornstarch appears to improve the quality of life of
      patients with GSD I without sacrificing metabolic control. Avoiding the overnight
      dose of cornstarch should enhance safety in this population.

PMID- 26303613
TI  - Antidepressant Regulatory Warnings, Prescription Patterns, Suicidality and Other
      Aggressive Behaviors in Major Depressive Disorder and Anxiety Disorders.
AB  - In 2004 the Food and Drug Administration issued a warning on the risk of
      suicidality in children and adolescents receiving antidepressants. This was
      followed by reports of changes in antidepressant prescription patterns,
      suicidality and other aggressive behaviors, but debate is continuing regarding
      the nature and magnitude of these changes. We examined a large physician database
      for impact of the warning on antidepressant prescriptions, suicidality and other
      aggressive behaviors in major depressive disorder (MDD) and anxiety disorders in
      adult and pediatric patients. We analyzed electronic database covering over
      100,000 patients, treated in Pre- (before 2003) and Post- (after 2004) warning
      periods. We compared strength of the association between the measures and the
      time period with two tests. Multivariate logistic regression analyses were
      performed to ascertain the unique effect of each parameter. Of 10,089 MDD (61.0
      %) and anxiety disorders (39.0 %) patients, 65.2 % received antidepressant
      prescription and 16.1 % were pediatric patients. In post-warning period, there
      was a greater reduction in adult versus pediatric antidepressant prescription
      rates. Logistic modeling showed greater likelihood of antidepressant prescription
      in MDD as compared with anxiety disorders in post-warning period. Pediatric
      patients were more likely than adults to receive fluoxetine during the post
      warning period. There was an overall reduction in suicidality and other
      aggressive behaviors in the post-warning period. Regulatory warnings may have had
      an impact on antidepressant benefit/risk assessment and consequent utilization,
      therapeutic effects, and adverse events. Our observations suggest that
      psychiatrists may heed regulatory warnings, but may also exert professional
      independence and discrimination in their application.

PMID- 26303614
TI  - Helping Mothers Survive Bleeding After Birth: retention of knowledge, skills, and
      confidence nine months after obstetric simulation-based training.
AB  - BACKGROUND: It is important to know the decay of knowledge, skills, and
      confidence over time to provide evidence-based guidance on timing of follow-up
      training. Studies addressing retention of simulation-based education reveal mixed
      results. The aim of this study was to measure the level of knowledge, skills, and
      confidence before, immediately after, and nine months after simulation-based
      training in obstetric care in order to understand the impact of training on these
      components. METHODS: An educational intervention study was carried out in 2012 in
      a rural referral hospital in Northern Tanzania. Eighty-nine healthcare workers of
      different cadres were trained in "Helping Mothers Survive Bleeding After Birth",
      which addresses basic delivery skills including active management of third stage
      of labour and management of postpartum haemorrhage (PPH). Knowledge, skills, and
      confidence were tested before, immediately after, and nine months after training
      amongst 38 healthcare workers. Knowledge was tested by completing a written 26
      item multiple-choice questionnaire. Skills were tested in two simulated scenarios
      "basic delivery" and "management of PPH". Confidence in active management of
      third stage of labour, management of PPH, determination of completeness of the
      placenta, bimanual uterine compression, and accessing advanced care was self
      assessed using a written 5-item questionnaire. RESULTS: Mean knowledge scores
      increased immediately after training from 70 % to 77 %, but decreased close to
      pre-training levels (72 %) at nine-month follow-up (p = 0.386) (all p-levels are
      compared to pre-training). The mean score in basic delivery skills increased
      after training from 43 % to 51 %, and was 49 % after nine months (p = 0.165).
      Mean scores of management of PPH increased from 39 % to 51 % and were sustained
      at 50 % at nine months (p = 0.003). Bimanual uterine compression skills increased
      from 19 % before, to 43 % immediately after, to 48 % nine months after training
      (p = 0.000). Confidence increased immediately after training, and was largely
      retained at nine-month follow-up. CONCLUSIONS: Training resulted in an immediate
      increase in knowledge, skills, and confidence. While knowledge and simulated
      basic delivery skills decayed after nine months, confidence and simulated
      obstetric emergency skills were largely retained. These findings indicate a need
      for continuation of training. Future research should focus on the frequency and
      dosage of follow-up training.

PMID- 26303615
TI  - Detecting changes in arthritic fibroblast-like synoviocytes using atomic force
      microscopy.
AB  - The morphological and quantitative differences between arthritic fibroblast-like
      synoviocytes (FLS) and normal FLS were determined as an effective diagnostic tool
      for rheumatoid arthritis (RA), and confirmed using atomic force microscopy (AFM).
      Collagen-induced arthritic (CIA) mice and normal mice were prepared and FLS were
      isolated by enzymatic digestion from the synovial tissue of sacrificed mice at 5
      week and 8-week pathogenesis periods. Analysis of cell morphology using AFM
      revealed that the surface roughness around the nucleus and around the branched
      cytoplasm was significantly higher in CIA FLS (P < 0.05) than that in normal FLS.
      In addition, the roughness of two different sites on the arthritic FLS increased
      with an increase in the duration of pathogenesis. These results strongly suggest
      that AFM can be widely used as a diagnostic tool in cytopathology to detect the
      early signs of RA and various others diseases at the intercellular level.

PMID- 26303616
TI  - The role of underestimating body size for self-esteem and self-efficacy among
      grade five children in Canada.
AB  - PURPOSE: Underestimating body size hinders healthy behavior modification needed
      to prevent obesity. However, initiatives to improve body size misperceptions may
      have detrimental consequences on self-esteem and self-efficacy. METHODS: Using
      sex-specific multiple mixed-effect logistic regression models, we examined the
      association of underestimating versus accurate body size perceptions with self
      esteem and self-efficacy in a provincially representative sample of 5075 grade
      five school children. Body size perceptions were defined as the standardized
      difference between the body mass index (BMI, from measured height and weight) and
      self-perceived body size (Stunkard body rating scale). Self-esteem and self
      efficacy for physical activity and healthy eating were self-reported. RESULTS:
      Most of overweight boys and girls (91% and 83%); and most of obese boys and girls
      (93% and 90%) underestimated body size. Underestimating weight was associated
      with greater self-efficacy for physical activity and healthy eating among normal
      weight children (odds ratio: 1.9 and 1.6 for boys, 1.5 and 1.4 for girls) and
      greater self-esteem among overweight and obese children (odds ratio: 2.0 and 6.2
      for boys, 2.0 and 3.4 for girls). CONCLUSIONS: Results highlight the importance
      of developing optimal intervention strategies as part of targeted obesity
      prevention efforts that de-emphasize the focus on body weight, while improving
      body size perceptions.

PMID- 26303617
TI  - Usefulness of a home affluence scale administered to urban adolescents with
      asthma to estimate the family's socioeconomic status.
AB  - PURPOSE: Measurement of socioeconomic status (SES) is traditionally based on
      education, income, and occupation. This information may not be readily available
      from adolescents participating in research. METHODS: Using data from school-based
      randomized trial of an asthma intervention targeting urban adolescents, we
      compared percent poverty in zip code of residence (% poverty), median housing
      value, and parental income and education, to teen responses on the Home Affluence
      Scale for Children (HASC), which included home, car, and computer ownership for
      the family and eligibility for free school lunch. The association of HASC with
      measures of asthma control was also assessed. RESULTS: Of 422 adolescents, 390
      (92%) responded to HASC items (mean HASC = 2.5). HASC was associated with
      mother's education and household income (both P < .001), and significantly
      correlated with % poverty (P < .0001) and median home value (P = .003). The
      association of HASC <2.0 to indicators of uncontrolled asthma was in the
      direction hypothesized, especially for nighttime symptoms, odds ratio (95%
      confidence interval) = 1.59 (0.95-2.66) and restricted activity, odds ratio =
      1.87 (1.12-3.12). CONCLUSIONS: HASC correlates well with more traditional
      measures of SES, and the risk estimates for HASC less than 2.0 and indicators of
      uncontrolled asthma were mostly in the hypothesized direction. Methods of
      obtaining SES indicators from youth are needed for research studies.

PMID- 26303618
TI  - Phase I clinical trial of autologous NK cell therapy using novel expansion method
      in patients with advanced digestive cancer.
AB  - BACKGROUND: NK cells can destroy tumor cells without prior sensitization or
      immunization. Tumors often lose expression of MHC molecules and/or antigens.
      However, NK cells can lyse tumor cells in a non-MHC-restricted manner and
      independent of the expression of tumor-associated antigens. NK cells are
      therefore considered ideal for adoptive cancer immunotherapy; however the
      difficulty of obtaining large numbers of fully functional NK cells that are safe
      to administer deters its clinical use. This phase I clinical trial seeks to
      address this obstacle by first developing a novel system that expands large
      numbers of highly activated clinical grade NK cells, and second, determining if
      these cells are safe in a mono-treatment so they can be combined with other
      reagents in the next round of clinical trials. METHODS: Patients with
      unresectable, locally advanced and/or metastatic digestive cancer who did not
      succeed with standard therapy were enrolled. NK cells were expanded ex vivo by
      stimulating PBMCs with OK432, IL-2, and modified FN-CH296 induced T cells.
      Patients were administered autologous natural killer cell three times weekly via
      intravenous infusions in a dose-escalating manner (dose 0.5 * 10(9), 1.0 * 10(9),
      2.0 * 10(9) cells/injection, three patients/one cohort). RESULTS: Total cell
      population had a median expansion of 586-fold (range 95-1102), with a
      significantly pure (90.96 %) NK cell population. Consequently, NK cells were
      expanded to approximately 4720-fold (range 1372-14,116) with cells being highly
      lytic in vitro and strongly expressing functional markers such as NKG2D and CD16.
      This NK cell therapy was very well tolerated with no severe adverse events.
      Although no clinical responses were observed, cytotoxicity of peripheral blood
      was elevated approximately twofolds up to 4 weeks post the last transfer.
      CONCLUSION: We successfully generated large numbers of activated NK cells from
      small quantities of blood without prior purification of the cells. We also
      determined that the expanded cells were safe to administer in a monotherapy and
      are suitable for the next round of clinical trials where their efficacy will be
      tested combined with other reagents. TRIAL REGISTRATION: UMIN UMIN000007527.

PMID- 26303619
TI  - Suitability of stx-PCR directly from fecal samples in clinical diagnostics of
      STEC.
AB  - PCR-based testing for Shiga toxin producing Escherichia coli (STEC) directly from
      fecal samples is increasingly being implemented in routine diagnostic
      laboratories. These methods aim to detect clinically relevant amounts of microbes
      and not stx-carrying phages or low backgrounds of STEC. We present a diagnostic
      procedure and results from 1 year of stx-targeted real-time PCR of fecal samples
      from patients with gastrointestinal symptoms in Norway. A rapid stx2 subtyping
      strategy is described, which aims to quickly reveal the virulence potential of
      the microbe. stx was detected in 22 of 3320 samples, corresponding to a PCR
      positive rate of 0.66%. STEC were cultured from 72% of the PCR positive samples.
      Four stx1 isolates, eight stx2 isolates, and four isolates with both stx1 and
      stx2 were identified. With the method presented, stx-carrying phages are not
      commonly detected. Our results support the use of molecular testing combined with
      classical culture techniques for routine diagnostic purposes. 

PMID- 26303620
TI  - Regulatory Effect of Catalpol on Th1/Th2 cells in Mice with Bone Loss Induced by
      Estrogen Deficiency.
AB  - PROBLEM: Estradiol (E2 ) deficiency can cause bone loss and the skew of Th1/Th2
      cells. However, the correlation between the Th1/Th2 cells and the bone loss
      induced by estrogen deficiency remains unclear. Our aim was to investigate the
      role of Th1/Th2 in bone loss induced by estrogen deficiency and elucidated the
      therapeutical effect of catalpol in this condition. METHOD OF STUDY: Young, sham
      operated (Sham), ovariectomized (Ovx), and naturally aged mice, treated with
      catalpol at different doses or control vehicle, were used in this study as
      indicated in each experiment. ELISA assay, dual-energy X-ray absorptiometry, and
      flow cytometry were used to analyze E2 , C-terminal telopeptides of type I
      collagen (CTx-I), bone mineral density (BMD), and Th1/Th2 subsets, respectively.
      The mRNA and protein expressions of specific transcription factors for Th1/Th2
      cells (T-bet and GATA-3) were analyzed using real-time quantitative PCR and
      Western blot, respectively. RESULTS: Bone mineral density and E2 levels
      positively correlated with the proportion of Th2 subset while negatively
      correlated with that of Th1 subset and the ratio of Th1/Th2. Catalpol alleviated
      bone loss effectively by regulating Th1/Th2 polarization. Catalpol promoted the
      expression of Th2-specific transcription factors while inhibited that associated
      with Th1. CONCLUSION: Th1/Th2 skew is involved in bone loss induced by estrogen
      deficiency. Catalpol alleviates bone loss effectively by regulating Th1/Th2
      paradigm.

PMID- 26303622
TI  - The Dynamics of Coalition Formation on Complex Networks.
AB  - Complex networks describe the structure of many socio-economic systems. However,
      in studies of decision-making processes the evolution of the underlying social
      relations are disregarded. In this report, we aim to understand the formation of
      self-organizing domains of cooperation ("coalitions") on an acquaintance network.
      We include both the network's influence on the formation of coalitions and vice
      versa how the network adapts to the current coalition structure, thus forming a
      social feedback loop. We increase complexity from simple opinion adaptation
      processes studied in earlier research to more complex decision-making determined
      by costs and benefits, and from bilateral to multilateral cooperation. We show
      how phase transitions emerge from such coevolutionary dynamics, which can be
      interpreted as processes of great transformations. If the network adaptation rate
      is high, the social dynamics prevent the formation of a grand coalition and
      therefore full cooperation. We find some empirical support for our main results:
      Our model develops a bimodal coalition size distribution over time similar to
      those found in social structures. Our detection and distinguishing of phase
      transitions may be exemplary for other models of socio-economic systems with low
      agent numbers and therefore strong finite-size effects. 

PMID- 26303623
TI  - Vitamin D deficiency in multiple sclerosis: Should testing and treatment be based
      on racial background?
AB  - Maintaining adequate levels of vitamin D may have a protective effect and lower
      the risk of multiple sclerosis (MS). For patients with MS, maintaining an
      adequate level of vitamin D level is probably associated with lessening of the
      frequency and severity of their symptoms. However, what remains unclear is
      whether if this is true across all racial/ethnic backgrounds. In African
      Americans (AAs) this effect is not only absent but curiously enough, low levels
      of vitamin D do not matter since the bioavailability of this molecule in AA
      subjects is normal. It is this paradox that led to this brief report and we
      suggest more research and database construction based on race/ethnicity be done,
      as a first step to understand the biological mechanisms that confer or negate the
      effect of vitamin D levels in MS. 

PMID- 26303624
TI  - The burden of distress and related coping processes in family caregivers of
      patients with Alzheimer's disease living in the community.
AB  - BACKGROUND: Many patients with dementia live in the community and depend on a
      family member for assistance. Taking care of non-self-sufficient people such as
      those with dementia causes distress. This study concerns factors contributing to
      feelings of burden and consequent coping strategies adopted by family caregivers
      of patients with Alzheimer's disease living in the community. METHODS: The
      severity of the caregiver burden (Caregiver Burden Inventory and the
      Neuropsychiatric Inventory Caregiver Distress Scale) was evaluated in relation to
      the cognitive, behavioral, functional, mood, motor and comorbidity status in 73
      consecutive patients with Alzheimer's disease. The type of coping processes
      (Coping Orientation to Problem Experienced), and psychosocial and medical
      variables of caregivers were also investigated and correlated with the degree of
      their distress. RESULTS: The amount of burden for caregivers, was found to be
      positively correlated with several measures of cognitive, psychological,
      behavioral, and motor impairment of the patients. The severity of caregiver
      distress was correlated with specific coping strategies, such as seeking for
      social support, using avoidance behaviors and focusing on problems. Finally,
      caregivers needing higher levels of familial and/or social support had also
      higher levels of distress. CONCLUSIONS: Higher cognitive, psychological,
      behavioral, and motor impairment of patients with Alzheimer's disease are
      associated with increasing levels of burden and distress in their caregivers, who
      need to adopt adequate coping strategies and to seek for familial and social
      support.

PMID- 26303625
TI  - Devic's disease before Devic: Bilateral optic neuritis and simultaneous myelitis
      in a young woman (1874).
AB  - Neuromyelitis optica (NMO, Devic's disease) is an often severely disabling
      disorder of the central nervous system (CNS) which mainly affects the optic
      nerves and spinal cord. NMO was long considered a clinical subform of multiple
      sclerosis (MS). In 2004, however, Lennon and colleagues described a novel
      autoantibody in NMO which targets aquaporin-4, the most abundant water channel in
      the CNS, and which was later shown to be directly pathogenic. This has led to the
      recognition of NMO as a distinct disease entity in its own right. While the
      history of 'classical' MS has been extensively studied, only little is known
      about the early history of NMO. The term neuromyelitis optica was coined in 1894
      by Eugene Devic (1858-1930) and Fernand Gault (1873-1936), who were the first to
      provide a systematic description of that disorder. Here we re-present a very
      early description of a case of NMO by a Polish physician, Adolf Wurst, which
      appeared in 1876 in Przeglad Lekarski, one of the oldest Polish medical journals.
      This report predates Devic and Gault's seminal work on NMO by more than two
      decades. The patient, a 30-year-old woman, subacutely developed simultaneous
      bilateral optic neuritis with papilloedema and bilateral blindness and transverse
      myelitis with severe paraparesis, anaesthesia, and bladder and bowel dysfunction.
      At last follow-up, one year after onset, she had recovered except for a residual
      spastic gait and some visual deficit on the right side. Of note, this is the
      first known case of NMO in a Caucasian patient ever reported outside Western
      Europe.

PMID- 26303627
TI  - Determinants of anterior chamber depth in a large Caucasian population and
      agreement between intra-ocular lens Master and Pentacam measurements of this
      variable.
AB  - PURPOSE: To establish the main determinants of anterior chamber depth (ACD) in
      Caucasian subjects and examine agreement between IOL Master((r)) (Carl Zeiss,
      Meditec) and Pentacam((r)) (Oculus Inc.) ACD measurements. METHODS: In a cross
      sectional study, 1006 right eyes of 1006 healthy subjects were subjected to a
      general ophthalmologic examination using the Pentacam((r)) , IOLMaster((r)) and
      OCT RTVue((r)) (Optovue Inc.). The variables recorded were age, sex, intra-ocular
      pressure, spherical refractive error, axial length (AL), central corneal
      thickness, corneal diameter, iris thickness, and anterior chamber depth, volume
      and angle (ACA). The effects of these variables on ACD were analysed by
      multivariate linear regression. RESULTS: Mean age was 49.1 years (range 18-84);
      61% were women. In 98.3% of the eyes, ACD could be measured using the IOL Master
      and in 98% the Pentacam was used to give mean depths of 3.30 +/- 0.42 mm and 3.35
      +/- 0.43 mm, respectively, for the two instruments. Agreement between these
      devices was high. In men, ACD was 0.13 mm on average deeper than in women (p <
      0.001). ACD was correlated with ACA, AL, corneal diameter, spherical refractive
      error and age (p < 0.001). Five variables - age, sex, spherical error, corneal
      diameter and ACA - were able to explain 74.1% of the variation produced in ACD
      (R(2) = 0.741; p < 0.001), among which age emerged as the main determinant
      (partial R(2) = 0.279; p < 0.001). CONCLUSIONS: Age, sex, spherical error,
      corneal diameter and ACA correlate highly with ACD and together serve to explain
      much of its variation. When used to measure ACD, the IOLMaster and Pentacam show
      excellent agreement.

PMID- 26303626
TI  - Prevention of Morbidity in sickle cell disease--qualitative outcomes, pain and
      quality of life in a randomised cross-over pilot trial of overnight supplementary
      oxygen and auto-adjusting continuous positive airways pressure (POMS2a): study
      protocol for a randomised controlled trial.
AB  - BACKGROUND: Sickle cell anaemia (SCA) is an inherited disorder of haemoglobin.
      Patients experience long-term health care problems, affecting quality of life
      (QOL) including frequent acute pain, which is difficult to document in trials
      except as hospital admissions. Pilot data suggests that overnight respiratory
      support, either supplementary oxygen or auto-adjusting continuous positive
      airways pressure (APAP), is safe and may have clinical benefit. This pilot trial
      aims to determine which intervention is more acceptable to participants and
      whether there are other advantages of one over the other, e.g. in respiratory
      function or haematological parameters, before conducting the Phase 2 trial of
      overnight respiratory support funded by the National Institutes of Health
      Research. METHODS/DESIGN: This is a pilot cross-over interventional trial with
      the order of interventions decided by simple randomization. Ten adults (age over
      18 years) and 10 children (aged between 8 and 18 years) with homozygous sickle
      cell disease (haemoglobin SS, HbSS), recruited regardless of symptoms of sleep
      disordered breathing, will undergo overnight pulse oximetry and will have two
      interventions, overnight oxygen and APAP, for a week each in randomised order
      with a washout week between interventions. Participants will complete online
      diaries via an iPad throughout the 29 days of the study and will complete QOL
      questionnaires and have measurement of haematology, biochemistry, spirometry and
      lung volumes (adults only) at 3 time points, at baseline and after each
      intervention, as well as in-depth semi-structured qualitative interviews after
      each intervention, carried out by an experienced psychologist. Both qualitative
      and statistical methods will be used to analyze the data. The primary outcome is
      qualitative data looking at participant experience from the transcribed
      interviews after each intervention. The participant's view on feasibility,
      acceptability and preference will specifically be explored. The QOL, laboratory
      and lung function data will be compared with baseline for each arm. DISCUSSION:
      Patient and public involvement is an integral part of this trial and the key
      outcome is the qualitative result, which is dependent on obtaining good quality
      data to advise on participant feasibility, acceptability and preference. This is
      being addressed by using a standard interview. The development of a pain endpoint
      is another important outcome and collecting daily measurements is likely to be
      challenging. Research results will be used to inform design of the Phase 2 trial.
      TRIAL REGISTRATION: ISRCTN46078697 18 July 2014.

PMID- 26303628
TI  - [Augmentation technique on the proximal humerus].
AB  - BACKGROUND AND OBJECTIVES: The treatment of osteoporotic fractures is still a
      challenge. The advantages of augmentation with respect to primary in vitro
      stability and the clinical use for the proximal humerus are presented in this
      article. MATERIAL AND METHODS: In this study six paired human humeri were
      randomized into an augmented and a non-augmented group. Osteosynthesis was
      performed with a PHILOS plate (Synthes(r)). In the augmented group the two screws
      finding purchase in the weakest cancellous bone were augmented. The specimens
      were tested in a 3-part fracture model in a varus bending test. RESULTS: The
      augmented PHILOS plates withstood significantly more load cycles until failure.
      The correlation to bone mineral density (BMD) showed that augmentation could
      partially compensate for low BMD. CONCLUSION: The augmentation of the screws in
      locked plating in a proximal humerus fracture model is effective in improving the
      primary stability in a cyclic varus bending test. The targeted augmentation of
      two particular screws in a region of low bone quality within the humeral head was
      almost as effective as four screws with twice the amount of bone cement. Screw
      augmentation combined with a knowledge of the local bone quality could be more
      effective in enhancing the primary stability of a proximal humerus locking plate
      because the effect of augmentation can be exploited more effectively limiting it
      to the degree required. The technique of augmentation is simple and can be
      applied in open and minimally invasive procedures. When the correct procedure is
      used, complications (cement leakage into the joint) can be avoided.

PMID- 26303630
TI  - Anomalous behavior of visible light active TiO2 for the photocatalytic
      degradation of different Reactive dyes.
AB  - Nanocrystalline undoped, N-doped, N and metal codoped titania with different
      particle size, surface area, anatase phase content, crystallinity, band gap and
      zeta potential were synthesized by the sol-gel method. The photocatalytic
      activities of the synthesized TiO2 powders were compared by employing four
      different Reactive dyes. The order of photocatalytic activity observed for
      Reactive Red 198 dye (RR 198) was undoped = N,Cu codoped = N-doped > N,Fe codoped
      TiO2, Reactive Blue 4 dye (RB 4) was N,Cu codoped > N,Fe codoped > N-doped >
      undoped TiO2, Reactive Black 5 dye (RB 5) was N,Cu codoped* > undoped > N-doped >
      N,Fe codoped TiO2 and negligible degradation was observed for Reactive Orange 16
      dye (RO 16). In this paper, the anomalous trend of the photocatalytic activity of
      various photocatalysts for the degradation of a particular class of dyes has been
      observed and accounted for based upon three parameters: mechanism of degradation,
      physicochemical properties of the catalyst and adsorption behavior based on the
      zeta potential. It was concluded that apart from these parameters, the substrate
      specificity of the catalyst is also of equal importance in developing new
      catalysts for the photodegradation of dyes present in textile effluents. 

PMID- 26303629
TI  - [Balloon osteoplasty as reduction technique in the treatment of tibial head
      fractures].
AB  - BACKGROUND: Tibial plateau fractures requiring surgery are severe injuries of the
      lower extremities. Depending on the fracture pattern, the age of the patient, the
      range of activity and the bone quality there is a broad variation in adequate
      treatment.  AIM: This article reports on an innovative treatment concept to
      address split depression fractures (Schatzker type II) and depression fractures
      (Schatzker type III) of the tibial head using the balloon osteoplasty technique
      for fracture reduction. METHODS: Using the balloon technique achieves a precise
      and safe fracture reduction. This internal osteoplasty combines a minimal
      invasive percutaneous approach with a gently rise of the depressed area and the
      associated protection of the stratum regenerativum below the articular cartilage
      surface. This article lights up the surgical procedure using the balloon
      technique in tibia depression fractures. CONCLUSION: Using the balloon technique
      a precise and safe fracture reduction can be achieved. This internal osteoplasty
      combines a minimally invasive percutaneous approach with a gentle raising of the
      depressed area and the associated protection of the regenerative layer below the
      articular cartilage surface. Fracture reduction by use of a tamper results in
      high peak forces over small areas, whereas by using the balloon the forces are
      distributed over a larger area causing less secondary stress to the cartilage
      tissue. This less invasive approach might help to achieve a better long-term
      outcome with decreased secondary osteoarthritis due to the precise and
      chondroprotective reduction technique.

PMID- 26303632
TI  - Time to Look Underneath the Surface: Ulcerative Colitis-Associated Fibrosis.

PMID- 26303631
TI  - Isolation, selection and culture methods to enhance clonogenicity of mouse bone
      marrow derived mesenchymal stromal cell precursors.
AB  - INTRODUCTION: Conventionally cultured mouse bone marrow mesenchymal stromal cells
      (mBM-MSC) are a heterogeneous population that often initially contain
      contaminating haematopoietic cells. Variability in isolation methods, culture
      protocols and the lack of specific mBM MSC markers might explain this
      heterogeneity. The aim of this study is to optimise the isolation, culture
      conditions and selection of mBM-MSC. METHODS: Mouse BM-MSCs were isolated from
      crushed long bones (cBM) or flushed bone marrow (fBM) from 6-8 week old C57Bl/6
      mice. These subpopulations were analysed by flow cytometry using commonly used
      mBM-MSC cell surface marker, e.g. Sca-1, CD29 and CD44. Cells were cultured and
      expanded in vitro in hypoxic conditions of either 2 % or 5 % oxygen. Cell sorting
      and qRT-PCR was used to determine transcript levels of stem cell and lineage
      related genes in individual subpopulations. RESULTS: During early passaging not
      only do contaminating haematopoietic cells disappear, but there is a change in
      the phenotype of mBM-MSC affecting particularly CD44 and Sca-1 expression. By
      fluorescence activated cell sorting of CD45(-)/Ter119(-) mBM stroma based on Sca
      1 expression and expansion in hypoxic conditions, we show that Sca-1(+) cells had
      higher CFU-F frequencies and showed enhanced proliferation compared with Sca-1(-)
      cells. As evaluated by in vitro assays and qRT-PCR, these cells presented in
      vitro tri-lineage differentiation along osteocyte, chondrocyte, and adipocyte
      lineages. Finally, by prospective isolation of Sca-1(+)PDGFRalpha(+)CD90(+) cells
      we have isolated mBM-MSC on a single cell level, achieving a CFU-F frequency of
      1/4. Functional investigations demonstrated that these MSC clones inhibited T
      lymphocyte proliferation. CONCLUSION: By positive selection using a combination
      of antibodies to Sca-1, CD90 and PDGFRalpha and culturing in hypoxia, we have
      found a subpopulation of BM cells from C57Bl/6 mice with a CFU-F cloning
      efficiency of 1/4. To our knowledge these results represent the highest
      frequencies of mouse MSC cloning from C57Bl/6 mice yet reported.

PMID- 26303633
TI  - Intraperitoneal Administration of Autologous Tolerogenic Dendritic Cells for
      Refractory Crohn's Disease: A Phase I Study.
AB  - BACKGROUND AND AIMS: Ex vivo-generated autologous tolerogenic dendritic cells
      [tolDCs] can restore immune tolerance in experimental colitis. The aim of this
      study was to determine the safety and tolerability of administration of
      autologous tolDCs in refractory Crohn's disease [CD] patients. METHODS: A phase
      I, single-centre, sequential-cohorts, dose-range study was designed. Stable
      tolDCs were generated ex vivo from monocytes following a previously developed
      protocol, and administered by sonography-guided intraperitoneal injection. Six
      sequential refractory-CD cohorts were established: the first three cohorts
      received a single intraperitoneal injection of tolDCs at escalating doses [2 x
      10(6)/5 x 10(6)/10 x 10(6)]; and the last three cohorts received three biweekly
      intraperitoneal injections at same escalating doses. Safety was sequentially
      evaluated. Patients were assessed from week 0 to 12 and followed up for 1-year
      period for safety. RESULTS: Nine patients were included. No adverse effects were
      detected during tolDC injection or follow-up. Three patients withdrew from the
      study due to CD worsening. Crohn's Disease Activity Index [CDAI] decreased from
      274 [60] {mean (standard deviation [SD])} to 222 [113] [p = 0.3]; one [11%]
      patient reached clinical remission [CDAI < 150] and two [22%] clinical response
      [CDAI decrease >= 100]. Crohn's Disease Endoscopic Index of Severity [CDEIS]
      decreased from 18 [5] to 13 [8] [p = 0.4]; lesions improved markedly in three
      patients [33%]. Quality of life (inflammatory bowel disease questionnaire [IBDQ])
      changed from 125 [27] to 131 [38] [p = 0.7]; remission [IBDQ at Week 12 >= 170]
      was reached in one [11%] case and response [IBDQ score increase >= 16] in two
      [22%]. CONCLUSIONS: Intraperitoneal administration of autologous tolDCs appears
      safe and feasible in refractory CD patients. Further studies should be developed
      to test clinical benefit, determine the optimal administration route and dose,
      and monitor the immune responses; See [www.eudract.ema.europa.eu, EudraCT number
      2007-003469-42; www.aemps.gob.es number PEI 08-049].

PMID- 26303635
TI  - Outcome in Patients Having Salvage Coronary Artery Bypass Grafting.
AB  - Salvage coronary artery bypass grafting (CABG) is often performed for cardiogenic
      shock on compassionate basis without clinical data justifying this aggressive
      approach. The aim of this study was to analyze early and intermediate outcomes
      after salvage CABG. We retrospectively reviewed the data of 85 patients who
      underwent salvage CABG at 11 European cardiac surgery centers. Salvage CABG was
      defined according to the EuroSCORE criteria, that is, a procedure performed in
      patients requiring cardiopulmonary resuscitation (external cardiac massage) en
      route to the operating theater or before induction of anesthesia. A percutaneous
      coronary intervention procedure preceded salvage CABG in 55 patients (64.7%).
      Thirty patients (35.3%) died during the inhospital stay. The mean EuroSCORE II
      was 32.0% and the observed-to-expected ratio was 1.08. Salvage CABG was
      associated with high rates of postoperative stroke (9.4%), resternotomy for
      bleeding (23.5%), resternotomy for hemodynamic instability (15.3%), dialysis
      (18.8%), severe gastrointestinal complications (12.9%), and deep sternal wound
      infection (10.6%). Survival at 1, 3, and 5 years was 58.6%, 49.8%, and 40.9%,
      respectively. Twenty patients (23.5%) were postoperatively treated with
      extracorporeal membrane oxygenation (ECMO). The rates of adverse events after
      ECMO were particularly high (stroke 40%, resternotomy for bleeding 60%, dialysis
      35%, gastrointestinal complications 30%, and deep sternal wound infection 30%).
      Of patients treated with ECMO, 8 (40%) survived to discharge, and 1-year survival
      was 29.2%. Salvage CABG is associated with high risk of immediate mortality and
      severe adverse events. However, the observed immediate and intermediate outcome
      justify coronary surgery in these critically ill patients. A number of these
      patients are currently treated by ECMO, and its results are encouraging. 

PMID- 26303634
TI  - Associations Between Day of Admission and Day of Surgery on Outcome and Resource
      Utilization in Infants With Hypoplastic Left Heart Syndrome Who Underwent Stage I
      Palliation (from the Single Ventricle Reconstruction Trial).
AB  - Newborns with hypoplastic left heart syndrome and other single right ventricular
      variants require substantial health care resources. Weekend acute care has been
      associated with worse outcomes and increased resource use in other populations
      but has not been studied in patients with single ventricle. Subjects of the
      Single Ventricle Reconstruction trial were classified by whether they had a
      weekend admission and by day of the week of Norwood procedure. The primary
      outcome was hospital length of stay (LOS); secondary outcomes included transplant
      free survival, intensive care unit (ICU) LOS, and days of mechanical ventilation.
      The Student's t test with log transformation and the Wilcoxon rank-sum test were
      used to analyze associations. Admission day was categorized for 533 of 549
      subjects (13% weekend). The day of the Norwood was Thursday/Friday in 39%. There
      was no difference in median hospital LOS, transplant-free survival, ICU LOS, or
      days ventilated for weekend versus non-weekend admissions. Day of the Norwood
      procedure was not associated with a difference in hospital LOS, transplant-free
      survival, ICU LOS, or days ventilated. Prenatally diagnosed infants born on the
      weekend had lower mean birth weight, younger gestational age, and were more
      likely to be intubated but did not have a difference in measured outcomes. In
      conclusion, in this cohort of patients with single right ventricle, neither
      weekend admission nor end-of-the-week Norwood procedure was associated with
      increased use of hospital resources or poorer outcomes. We speculate that the
      complex postoperative course following the Norwood procedure outweighs any impact
      that day of admission or operation may have on these outcomes. 

PMID- 26303636
TI  - Risk Factors for Prosthetic Pulmonary Valve Failure in Patients With Congenital
      Heart Disease.
AB  - The incidence and risk factors for prosthetic pulmonary valve failure (PPVF)
      should be considered when determining optimal timing for pulmonary valve
      replacement (PVR) in asymptomatic patients with congenital heart disease (CHD).
      The cumulative freedom for reintervention due to PPVF after 146 PVR in 114
      patients with CHD was analyzed. Six potential risk factors (underlying cardiac
      defect, history of palliative procedures, number of previous cardiac
      interventions, hemodynamic indication for PVR, type of intervention, and age at
      intervention) were analyzed using Cox proportional hazard modeling. Receiver
      operating characteristic (ROC) curves were used for discrimination. Internal
      validation in patients with tetralogy of Fallot was also performed. Median age at
      intervention was 23 years. There were 60 reinterventions due to PPVF (41%).
      Median event-free survival was 14 years (95% confidence interval [CI] 12 to 16
      years). The only independent risk factor was the age at intervention (hazard
      ratio [HR] 0.93, 95% CI 0.90 to 0.97; p = 0.001; area under the ROC curve 0.95,
      95% CI 0.92 to 0.98; p <0.001). The best cut-off point was 20.5 years. Freedom
      from reintervention for PPVF 15 years after surgery was 70% when it was performed
      at age >20.5 years compared with 33% when age at intervention was <20.5 years (p
      = 0.004). Internal validation in 102 PVR in patient cohort with tetralogy of
      Fallot (ROC area 0.98, 95% CI 0.96 to 1.0; p <0.001) was excellent. In
      conclusion, age at intervention is the main risk factor of reintervention for
      PPVF. The risk of reintervention is 2-fold when PVR is performed before the age
      of 20.5 years. 

PMID- 26303637
TI  - Virulence genotyping and population analysis of Streptococcus suis serotype 2
      isolates from China.
AB  - Streptococcus suis is one of the most important swine pathogens worldwide. In
      this study, a total of 22 virulence-related genes in 101 strains of S. suis
      serotype 2 (SS2) were detected by PCR, namely, mrp, epf, sly, fbps, rgg, ofs,
      srtA, pgdA, gapdh, iga, endoD, ciaRH, salKR, manN, purD, rgg, DppIV, neuB, dltA,
      SMU_61-like, SpyM3_0908 (Permease) and the SspA gene. The distribution of
      virulence-related genes among isolates was visualized using BioNumerics software
      to study similarities among the isolates. Two clusters of SS2 were apparent on
      the phylogenetic tree, namely, Clusters A and B. Both mouse and zebrafish
      infection models revealed that strains in Cluster B were more virulent than those
      in Cluster A. Statistical comparison between the two clusters was performed, and
      structure analysis demonstrated that epf, sly, rgg, endoD, SMU_61-like and
      SpyM3_0908 were possible predictive markers for SS2 virulence. The transcription
      levels of highly prevalent genes in both clusters were detected by qRT-PCR in
      representative strains. For Cluster A isolates, the transcription levels of neuB,
      dltA, fbps and pgdA were significantly lower, but the transcription level of iga
      was significantly higher than that in Cluster B isolates. Although encoded in the
      genomes of the selected Cluster A isolates, DppIV and mrp genes were not
      expressed. These results revealed the genetic differences between virulent and
      low-virulence SS2 isolates from China and provide a better understanding of the
      SS2 pathogenic mechanism. 

PMID- 26303639
TI  - Efficacy and safety of intra-arterial steroid infusions in patients with steroid
      resistant gastrointestinal acute graft-versus-host disease.
AB  - There is no established second-line treatment for steroid-resistant acute graft
      versus-host disease (GVHD). We prospectively assessed the safety and efficacy of
      intra-arterial steroid infusions (IASIs) for steroid-resistant acute
      gastrointestinal (GI) GVHD and compared the outcomes with those of historical
      controls at our institution. Nineteen consecutive, allogeneic hematopoietic stem
      cell transplantation subjects aged 31-67 years (median 52) were enrolled between
      October, 2008, and November, 2012. Acute GVHD was confirmed by biopsy in all
      cases. The enrolled patients were treated with infusions of methylprednisolone
      into the mesenteric arteries and/or gastroduodenal and left gastric arteries.
      Fourteen consecutive patients who developed steroid-resistant acute GI GVHD
      between 2001 and 2008 were used as controls. For the primary endpoint at day 28,
      the overall and complete responses in the IASI group trended higher (79% vs. 42%,
      p = 0.066) and were significantly higher (63% vs. 21%, p = 0.033) than those in
      the control group. Although not statistically significant, owing to the small
      population, the crude day-180-nonrelapse mortality rate was about 20% lower and
      the day-180-overall-survival rate tended to be higher than the control (11% vs.
      29%, p = 0.222; 79% vs. 50%, p = 0.109, respectively). There were no serious IASI
      related complications. Our results suggest that IASI can safely provide excellent
      efficacy for refractory acute GI GVHD without increasing infection-related
      complications and may improve prognosis.

PMID- 26303640
TI  - Activated STING enhances Tregs infiltration in the HPV-related carcinogenesis of
      tongue squamous cells via the c-jun/CCL22 signal.
AB  - The negative role of the activated stimulator of IFN genes (STING) has been
      uncovered in autoinflammatory disease and cancer. However, the role of STING in
      virus-related carcinogenesis is not well known. Herein, HPV(+) tongue squamous
      cell carcinoma (TSCC) (n=25) and HPV(-) TSCC samples (n=25) were randomly
      collected and were verified by in situ hybridization (ISH) and p16
      immunohistochemistry (IHC) to assess the expression and activated status of STING
      through IHC. The results showed that the expression of STING was up-regulated
      during the development of TSCC. Interestingly, although the expression of STING
      showed no difference between HPV(+/-) TSCC samples, the activated status of STING
      with dark staining around the nucleus was observed in HPV(+) TSCC samples. The
      role of activated STING was analyzed in three cell lines by siRNA and indicated
      that activated STING had no impact on cell viability or apoptosis but promoted
      the induction of several immunosuppressive cytokines, e.g., IL-10, IDO and CCL22,
      which facilitated the infiltration of regulatory T cells (Tregs). Moreover,
      increased infiltration of Foxp3(+) Tregs along with increased expression of CCL22
      was confirmed in HPV(+) TSCC samples. An inhibitor of the MAPK/AP-1 pathway
      (U0126) and the silencing of c-jun significantly suppressed CCL22 induction and
      the recruitment of Tregs by activated STING. Furthermore, down-regulated miR-27
      was verified in independent fresh TSCC samples (n=50) and eight cell lines, which
      enhanced STING activation and led to increased CCL22 expression for Tregs
      recruitment in the TSCC microenvironment. Therefore, our findings provided
      distinct insight into the side effects of activated STING in HPV-related
      carcinogenesis. 

PMID- 26303642
TI  - Brain targeted PLGA nanocarriers alleviating amyloid-Beta expression and
      preserving basal survivin in degenerating mice model.
AB  - The chronic systemic administration of d-Galactose in C57BL/6J mice showed a
      relatively high oxidative stress, amyloid-beta expression and neuronal cell
      death. Enhanced expression of pyknotic nuclei, caspase-3 and reduced expression
      of neuronal integrity markers further confirmed the aforesaid insults. However,
      concomitant treatment with the recombinant protein (SurR9-C84A) and the anti
      transferrin receptor antibody conjugated SurR9-C84A (SurR9+TFN) nanocarriers
      showed a significant improvement in the disease status and neuronal health. The
      beauty of this study is that the biodegradable Food and Drug Administration (FDA)
      approved poly(lactic-co-glycolic acid) (PLGA) nanocarriers enhanced the
      biological half-life and the efficacy of the treatments. The nanocarriers were
      effective in lowering the amyloid-beta expression, enhancing the neuronal
      integrity markers and maintaining the basal levels of endogenous survivin that is
      essential for evading the caspase activation and apoptosis. The current study
      herein reports for the first time that the brain targeted SurR9-C84A nanocarriers
      alleviated the d-Galactose induced neuronal insults and has potential for future
      brain targeted nanomedicine application. 

PMID- 26303643
TI  - Dietary habits of Samoan adults in an urban Australian setting: a cross-sectional
      study.
AB  - OBJECTIVE: To describe key characteristics of the dietary habits of Samoans
      residing in Logan, Queensland and to compare these characteristics with
      comparable populations. DESIGN: Dietary intake was measured using a self
      administered structured questionnaire between December 2012 and March 2013.
      Demographic characteristics included age and sex. Questionnaire results were
      compared with data from samples of Brisbane residents of similar social and
      economic characteristics and Pacific Islanders in New Zealand. The association
      between demographic characteristics and diet was investigated. SETTING: Logan,
      Queensland, Australia. SUBJECTS: Samoans aged 16 years and older. RESULTS: A
      total of 207 Samoans participated, ninety-six (46 %) of whom were male. Of the
      participants, seventy-nine (38 %) were aged 16-29 years, sixty-three (30 %) were
      aged 30-49 years and sixty-five (31 %) were aged >=50 years. Younger adults were
      significantly more likely to eat hamburgers, pizza, cakes, savoury pastries,
      potato crisps, sweets and soft drinks (all variables P<0.001). Among Samoans,
      44.7 % consumed two or more pieces of fruit daily, compared with 43.8 % of
      comparable Brisbane residents (relative risk=1.0; 95 % CI 0.8, 1.2). Three or
      more servings of vegetables each day were consumed by 9.2 % of Samoans compared
      with 36.6 % of comparable Brisbane residents (relative risk=3.8; 95 % CI 2.5,
      6.0). CONCLUSIONS: Samoans are consuming significantly fewer vegetables and more
      discretionary foods than other populations. Socio-economic factors, length of
      stay in Australia and cultural practices may impact upon Samoans' diets. Further
      comprehensive studies on Samoans' dietary habits in Australia are recommended.

PMID- 26303644
TI  - A cluster-randomised quality improvement study to improve two inpatient stroke
      quality indicators.
AB  - BACKGROUND: Quality indicator collection and feedback improves stroke care. We
      sought to determine whether quality improvement training plus indicator feedback
      was more effective than indicator feedback alone in improving inpatient stroke
      indicators. METHODS: We conducted a cluster-randomised quality improvement trial,
      randomising hospitals to quality improvement training plus indicator feedback
      versus indicator feedback alone to improve deep vein thrombosis (DVT) prophylaxis
      and dysphagia screening. Intervention sites received collaborative-based quality
      improvement training, external facilitation and indicator feedback. Control sites
      received only indicator feedback. We compared indicators pre-implementation (pre
      I) to active implementation (active-I) and post-implementation (post-I) periods.
      We constructed mixed-effect logistic models of the two indicators with a random
      intercept for hospital effect, adjusting for patient, time, intervention and
      hospital variables. RESULTS: Patients at intervention sites (1147 admissions),
      had similar race, gender and National Institutes of Health Stroke Scale scores to
      control sites (1017 admissions). DVT prophylaxis improved more in intervention
      sites during active-I period (ratio of ORs 4.90, p<0.001), but did not differ in
      post-I period. Dysphagia screening improved similarly in both groups during
      active-I, but control sites improved more in post-I period (ratio of ORs 0.67,
      p=0.04). In logistic models, the intervention was independently positively
      associated with DVT performance during active-I period, and negatively associated
      with dysphagia performance post-I period. CONCLUSION: Quality improvement
      training was associated with early DVT improvement, but the effect was not
      sustained over time and was not seen with dysphagia screening. External quality
      improvement programmes may quickly boost performance but their effect may vary by
      indicator and may not sustain over time.

PMID- 26303645
TI  - Surgery of gastric cancer and esophageal cancer: Does age matter?
AB  - INTRODUCTION: In the past, elderly patients with upper GI cancers were excluded
      from surgery or multimodal treatment only due to their advanced age. In an aging
      society this way of patient selection seems to be questionable. The aim of this
      retrospective exploratory study was to investigate how patients with upper GI
      cancer over the age of 70 years differ from younger patients in the postoperative
      course and which parameters influence overall survival in older patient
      populations. PATIENTS AND METHODS: From 2002 to 2012 1,005 patients underwent
      resection of esophageal or gastric cancer at the University of Heidelberg. 272
      patients were older than 70 years and analyzed in subgroups (70-74 years: n =
      146; 75-79 years: n = 82; 80 years or older: n = 44). Patients older than 70
      years were compared to patients under 70 years (n = 733) with focus on
      differences in patients characteristics and outcome. Statistical analyses were
      made retrospectively on a prospective database. RESULTS: Fewer older patients
      were treated neoadjuvantly (< 70 years: 41.5%; > 70 years: 24.7%, P < 0.001) and
      extended resection (abdominothoracic approach) was applied less frequently
      compared to patients under 70 years (< 70 years: 38.9%; > 70 years: 19.9%, P <
      0.001). The pNM-category (HR 1.41/2.56) and R-status (HR 1.78) remain the most
      important predictive factor for survival (all < 0.001). Female patients had a
      longer survival than men over the age of 70 (84.9 vs. 23.5 months, P < 0.01).
      Patients over 80 years had a significant shortened overall survival (> 80 years:
      16.7 vs. < 70 years: 37.4 months) compared to the other subgroups (P < 0.001) and
      a significant increased in-hospital mortality (> 80 years: 20.5% vs. < 70 years:
      6.0%, P = 0.002). CONCLUSIONS: An exclusion from surgical therapy due to advanced
      age in general seems not to be justified. However, the decision for a surgical
      resection in patients over 80 years should be made with caution. pNM-categories
      and R0-resection remain the most important predictive factors for overall
      survival in all subgroups. No survival benefit for neoadjuvant treatment in
      patients over 70 years was found, while women survived longer than men. However,
      the decision concerning a (radio) chemotherapy should be made individually in
      each patient.

PMID- 26303641
TI  - Sirtuin regulation in aging and injury.
AB  - Sirtuins or Sir2 family of proteins are a class of NAD(+) dependent protein
      deacetylases which are evolutionarily conserved from bacteria to humans. Some
      sirtuins also exhibit mono-ADP ribosyl transferase, demalonylation and
      desuccinylation activities. Originally identified in the yeast, these proteins
      regulate key cellular processes like cell cycle, apoptosis, metabolic regulation
      and inflammation. Humans encode seven sirtuin isoforms SIRT1-SIRT7 with varying
      intracellular distribution. Apart from their classic role as histone deacetylases
      regulating transcription, a number of cytoplasmic and mitochondrial targets of
      sirtuins have also been identified. Sirtuins have been implicated in longevity
      and accumulating evidence indicate their role in a spectrum of diseases like
      cancer, diabetes, obesity and neurodegenerative diseases. A number of studies
      have reported profound changes in SIRT1 expression and activity linked to
      mitochondrial functional alterations following hypoxic-ischemic conditions and
      following reoxygenation injury. The SIRT1 mediated deacetylation of targets such
      as PGC-1alpha, FOXO3, p53 and NF-kappab has profound effect on mitochondrial
      function, apoptosis and inflammation. These biological processes and functions
      are critical in life-span determination and outcome following injury. Aging is
      reported to be characterized by declining SIRT1 activity, and its increased
      expression or activation demonstrated prolonged life-span in lower forms of
      animals. A pseudohypoxic state due to declining NAD(+) has also been implicated
      in aging. In this review we provide an overview of studies on the role of
      sirtuins in aging and injury. 

PMID- 26303646
TI  - Irrigant flow during photon-induced photoacoustic streaming (PIPS) using Particle
      Image Velocimetry (PIV).
AB  - OBJECTIVES: This study aimed to compare fluid movements generated from photon
      induced photoacoustic streaming (PIPS) and passive ultrasonic irrigation (PUI).
      MATERIALS AND METHODS: Particle Image Velocimetry (PIV) was performed using 6-MUm
      melamine spheres in water. Measurement areas were 3-mm-long sections of the canal
      in the coronal, midroot and apical regions for PIPS (erbium/yttrium-aluminium
      garnet (Er:YAG) laser set at 15 Hz with 20 mJ), or passive ultrasonic irrigation
      (PUI, non-cutting insert at 30% unit power) was performed in simulated root
      canals prepared to an apical size #30/0.04 taper. Fluid movement was analysed
      directly subjacent to the apical ends of ultrasonic insert or fiber optic tips as
      well as at midroot and apically. RESULTS: During PUI, measured average velocities
      were around 0.03 m/s in the immediate vicinity of the sides and tip of the
      ultrasonic file. Speeds decayed to non-measureable values at a distance of about
      2 mm from the sides and tip. During PIPS, typical average speeds were about ten
      times higher than those measured for PUI, and they were measured throughout the
      length of the canal, at distances up to 20 mm away. CONCLUSIONS: PIPS caused
      higher average fluid speeds when compared to PUI, both close and distant from the
      instrument. The findings of this study could be relevant to the debriding and
      disinfecting stage of endodontic therapy. CLINICAL RELEVANCE: Irrigation
      enhancement beyond needle irrigation is relevant to more effectively eradicate
      microorganisms from root canal systems. PIPS may be an alternative approach due
      to its ability to create high streaming velocities further away from the
      activation source compared to ultrasonic activation.

PMID- 26303647
TI  - Prevalence of periodontitis in individuals with human leukocyte antigens (HLA)
      A9, B15, A2, and B5.
AB  - OBJECTIVE: Human leukocyte antigens (HLA) have been associated with
      periodontitis. Previous studies revealed HLA-A9 and HLA-B15 as potential
      susceptibility factors, while HLA-A2 and HLA-B5 might have protective effects.
      The aim of the study was to verify these associations in a group of HLA-typed
      blood donors with previously unknown periodontal status. MATERIALS AND METHODS:
      In four German centers, 140 blood donors with known HLA class I status were
      enrolled and allocated to the following five groups: HLA-A9 (N = 24), HLA-B15 (N
      = 20), HLA-A2 (N = 30), HLA-B5 (N = 26), and controls (N = 40). Periodontal
      examination included the measurement of probing depths (PDs), clinical attachment
      level (CAL), bleeding on probing (BOP), and community periodontal index of
      treatment needs (CPITN). RESULTS: Carriers with HLA-A9 and HLA-B15 had higher
      values of mean PD (P < 0.0001), CAL (P < 0.0001), and BOP (P < 0.002) as well as
      sites with PD and CAL with >=4 and >=6 mm (P < 0.0003), respectively, than
      controls. Multiple regression analyses revealed HLA-A9, HLA-B15, and smoking as
      risk indicators for moderate to severe (CPITN 3-4; odds ratio (OR): 66.7, 15.3,
      and 5.1) and severe (CPITN 4; OR: 6.6, 7.4, and 3.8) periodontitis. HLA-A2 and
      HLA-B5 did not show any relevant associations. CONCLUSION: The present data
      support a role of HLA-A9 and HLA-B15 as susceptibility factors for periodontitis,
      whereas HLA-A2 and HLA-B5 could not be confirmed as resistance factors. CLINICAL
      RELEVANCE: Both HLA antigens A9 and B15 are potential candidates for periodontal
      risk assessment.

PMID- 26303650
TI  - Comparative study of different waste biomass for energy application.
AB  - Biomass is available in many varieties, consisting of crops as well as its
      residues from agriculture, forestry, and the agro-industry. These different
      biomass find their way as freely available fuel in rural areas but are also
      responsible for air pollution. Emissions from such solid fuel combustion to
      indoor, regional and global air pollution largely depend on fuel types,
      combustion device, fuel properties, fuel moisture, amount of air supply for
      combustion and also on climatic conditions. In both economic and environment
      point of view, gasification constitutes an attractive alternative for the use of
      biomass as a fuel, than the combustion process. A large number of studies have
      been reported on a variety of biomass and agriculture residues for their possible
      use as renewable fuels. Considering the area specific agriculture residues and
      biomass availability and related transportation cost, it is important to explore
      various local biomass for their suitability as a fuel. Maharashtra (India) is the
      mainstay for the agriculture and therefore, produces a significant amount of
      waste biomass. The aim of the present research work is to analyze different local
      biomass wastes for their proximate analysis and calorific value to assess their
      potential as fuel. The biomass explored include cotton waste, leaf, soybean
      waste, wheat straw, rice straw, coconut coir, forest residues, etc. mainly due to
      their abundance. The calorific value and the proximate analysis of the different
      components of the biomass helped in assessing its potential for utilization in
      different industries. It is observed that ash content of these biomass species is
      quite low, while the volatile matter content is high as compared to Indian Coal.
      This may be appropriate for briquetting and thus can be used as a domestic fuel
      in biomass based gasifier cook stoves. Utilizing these biomass species as fuel in
      improved cook-stove and domestic gasifier cook-stoves would be a perspective step
      in the rural energy and environmental sectors. This is important considering that
      the cleaner fuel like LPG is still not available in rural areas of many parts of
      the world. 

PMID- 26303648
TI  - Association of vdr, cyp27b1, cyp24a1 and mthfr gene polymorphisms with oral
      lichen planus risk.
AB  - OBJECTIVES: The current study investigated the association between VDR EcoRV
      (rs4516035), FokI (rs2228570), ApaI (rs7975232) and TaqI (rs731236), CYP27B1
      (rs4646536), CYP24A1 (rs2296241), and MTHFR (rs1801133) gene polymorphisms and
      risk of oral lichen planus (OLP) occurrence. MATERIALS AND METHODS: The study
      group consisted of 65 oral lichen planus patients and 100 healthy blood donors in
      the control group. Single nucleotide polymorphisms were genotyped by real time
      PCR or PCR-restriction fragment length polymorphism (RFLP) method. RESULTS:
      Heterozygous as well as mutated genotype of vitamin D receptor (VDR) FokI
      (rs2228570) polymorphism was associated with increased oral lichen planus risk in
      comparison with wild type genotype (odds ratio (OR) = 3.877, p = 0.017, OR =
      38.153, p = 0.001, respectively). A significantly decreased OLP risk was observed
      for heterozygous genotype of rs2296241 polymorphism in CYP24A1 gene compared with
      the wild type form (OR = 0.314, p = 0.012). VDR gene polymorphisms ApaI and TaqI
      were in linkage disequilibrium (D' = 0.71, r(2) = 0.22). Identified haplotype AT
      was associated with decreased OLP risk (OR = 0.592, p = 0.047). CONCLUSION: Our
      results highlight the possible important role of VDR FokI (rs2228570) and CYP24A1
      rs2296241 gene polymorphisms for oral lichen planus susceptibility. CLINICAL
      RELEVANCE: Identification of new molecular biomarkers could potentially
      contribute to determination of individuals with OLP predisposition.

PMID- 26303651
TI  - Review of household solid waste charges for developing countries--A focus on
      quantity-based charge methods.
AB  - Solid waste management has become a major issue in almost all municipalities
      especially in developing countries across the world. As more waste needs to be
      collected and disposed of in urban areas, the increased cost cannot be covered by
      the available funds in developing countries. Managing the Household Solid Waste
      (HSW) sector is very important as it is the main contributor of the waste that
      needs to be collected in residential areas. The reduction of the amount of HSW to
      be disposed of can be achieved by households themselves practising the "4R"
      activities: reducing, reusing, recycling and recovering. As a policy instrument,
      the Waste Management Charge (WMC) for HSW has shown much success in encouraging
      such activities all over the world. Given the already difficult context in which
      developing countries operate, it is important to careful consider what kind of
      charging system is implemented. Using available literature, this paper reviews
      the applicability of available charging methods, from a flat rate method, through
      to volume-based (bags, cans or tag/sticker) and weight-based charging methods.
      These charging methods were evaluated on the basis of overall cost, technology
      need possible other issues. By considering the conditions in developing
      countries, a 'pre-paid bag based charging method' could be suggested as the most
      suitable charging method for a WMC in Sri Lanka or other developing countries.
      The potential applicability of this method was also examined in the context of
      social, economic and political characteristics. Whilst the use of economic
      instruments, including WMC, was widely discussed in the literature, the selection
      of a charging method in the context of developing countries is rarely discussed.
      Having said that, this paper gives an insight to the policy makers in developing
      countries upon using pre-paid bag based charging method for HSW sector. It also
      provides recommendations regarding possible issues in implementing for developing
      countries where there is an absence of such a Quantity-Based Charging (QBC)
      system for the HSW sector. 

PMID- 26303652
TI  - Removal of toxic and alkali/alkaline earth metals during co-thermal treatment of
      two types of MSWI fly ashes in China.
AB  - This study aims to vaporize heavy metals and alkali/alkaline earth metals from
      two different types of fly ashes by thermal treatment method. Fly ash from a
      fluidized bed incinerator (HK fly ash) was mixed with one from a grate
      incinerator (HS fly ash) in various proportions and thermally treated under
      different temperatures. The melting of HS fly ash was avoided when treated with
      HK fly ash. Alkali/alkaline earth metals in HS fly ash served as Cl-donors to
      promote the vaporization of heavy metals during thermal treatment. With
      temperature increasing from 800 to 900 degrees C, significant amounts of Cl, Na
      and K were vaporized. Up to 1000 degrees C in air, less than 3% of Cl and Na and
      less than 5% of K were retained in ash. Under all conditions, Cd can be vaporized
      effectively. The vaporization of Pb was mildly improved when treated with HS fly
      ash, while the effect became less pronounced above 900 degrees C. Alkali/alkaline
      earth metals can promote Cu vaporization by forming copper chlorides.
      Comparatively, Zn vaporization was low and only slightly improved by HS fly ash.
      The low vaporization of Zn could be caused by the formation of Zn2SiO4, ZnFe2O4
      and ZnAl2O4. Under all conditions, less than 20% of Cr was vaporized. In a
      reductive atmosphere, the vaporization of Cd and Pb were as high as that in
      oxidative atmosphere. However, the vaporization of Zn was accelerated and that of
      Cu was hindered because the formation of Zn2SiO4, ZnFe2O4 and ZnAl2O4 and copper
      chloride was depressed in reductive atmosphere. 

PMID- 26303653
TI  - Waste incineration industry and development policies in China.
AB  - The growing pollution from municipal solid waste due to economic growth and
      urbanization has brought great challenge to China. The main method of waste
      disposal has gradually changed from landfill to incineration, because of the
      enormous land occupation by landfills. The paper presents the results of a study
      of the development status of the upstream and downstream of the waste
      incineration industry chain in China, reviews the government policies for the
      waste incineration power industry, and provides a forecast of the development
      trend of the waste incineration industry. 

PMID- 26303654
TI  - Georgenia subflava sp. nov., isolated from a deep-sea sediment.
AB  - A Gram-stain-positive, aerobic, motile and non-spore-forming actinobacterium,
      strain Y32T, was isolated from a deep-sea sediment of the western Pacific Ocean.
      Phylogenetic and phenotypic properties of the organism supported that it belonged
      to the genus Georgenia. Strain Y32T shared highest 16S rRNA gene sequence
      similarity of 97.8 % with Georgenia muralis 1A-CT, followed by Georgenia
      thermotolerans TT02-04T (97.4 %), Georgenia daeguensis 2C6-43T (97.2 %),
      Oceanitalea nanhaiensis JLT1488T (97.2 %), Georgenia ruanii YIM 004T (97.0 %) and
      Georgenia soli CC-NMPT-T3T (97.0 %). The organism grew in the presence of 0-10 %
      (w/v) NaCl, at 4-40  degrees C and at pH 6-11, with optimal growth occurring at
      30-35  degrees C, at pH 7 and in the presence of 3.5 % (w/v) NaCl. The polar
      lipid profile of strain Y32T consisted of diphosphatidylglycerol,
      phosphatidylglycerol, phosphatidylinositol and two phosphatidylinositol
      mannosides. Strain Y32T contained MK-8(H4) and MK-7(H4) as the major components
      of the menaquinone system, and anteiso-C15 : 0, iso-C15 : 0 and iso-C14 : 0 as
      the predominant fatty acids. Galactose was detected as the cell-wall sugar. The
      G+C content of the DNA was 71.2 mol%. Based on the results of phenotypic,
      genotypic and phylogenetic analyses, it is considered that strain Y32T represents
      a novel species of the genus Georgenia, for which the name Georgenia subflava sp.
      nov. is proposed. The type strain is Y32T ( = LMG 28101T = CGMCC 1.12782T = JCM
      19765T = MCCC 1A09955T).

PMID- 26303655
TI  - Anterior composite restorations: A systematic review on long-term survival and
      reasons for failure.
AB  - OBJECTIVE: In this study the literature was systematically reviewed to
      investigate the clinical longevity of anterior composite restorations. DATA:
      Clinical studies investigating the survival of anterior light-cured composite
      restorations with at least three years of follow-up were screened and main
      reasons associated with restoration failure were registered. SOURCES: PubMed,
      Scopus, and Cochrane databases were searched without restriction on date or
      language. Reference lists of eligible studies were hand-searched. The grey
      literature search was not made systematically. STUDY SELECTION: Two reviewers
      screened titles and/or abstracts of 2273 unique studies. In total, 41 studies
      were selected for full-text reading, from which 17 were included in the
      qualitative synthesis. The included studies evaluated the clinical performance of
      Class III and/or IV restorations (10 studies), which were placed due to caries,
      fracture, or replaced old restorations; veneers and full-coverage restorations
      placed for aesthetic reasons (five studies); and restorations in worn teeth (two
      studies). Annual failure rates (AFRs) were calculated for each study.
      CONCLUSIONS: In total, 1821 restorations were evaluated and the total failure
      rate was 24.1%. AFRs varied from 0 to 4.1% and survival rates varied from 53.4%
      to 100%. Class III restorations generally had lower AFRs than the other
      restorations. Few studies addressed factors associated with failure, which
      included adhesive technique, composite resin, retreatment risk, and time required
      to build-up the restoration. Fracture of tooth/restoration was the most common
      reason for failure, whereas failures related to aesthetic qualities (color,
      anatomical form, surface stain) were more frequent when restorations were placed
      for aesthetic reasons.

PMID- 26303656
TI  - Genetic censusing identifies an unexpectedly sizeable population of an endangered
      large mammal in a fragmented forest landscape.
AB  - BACKGROUND: As habitat degradation and fragmentation continue to impact wildlife
      populations around the world, it is critical to understand the behavioral
      flexibility of species in these environments. In Uganda, the mostly unprotected
      forest fragment landscape between the Budongo and Bugoma Forests is a potential
      corridor for chimpanzees, yet little is known about the status of chimpanzee
      populations in these fragments. RESULTS: From 2011 through 2013, we noninvasively
      collected 865 chimpanzee fecal samples across 633 km(2) and successfully
      genotyped 662 (77%) at up to 14 microsatellite loci. These genotypes corresponded
      to 182 chimpanzees, with a mean of 3.5 captures per individual. We obtained
      population size estimates of 256 (95% confidence interval 246-321) and 319 (288
      357) chimpanzees using capture-with-replacement and spatially explicit capture
      recapture models, respectively. The spatial clustering of associated genotypes
      suggests the presence of at least nine communities containing a minimum of 8-33
      individuals each. Putative community distributions defined by the locations of
      associated genotypes correspond well with the distribution of 14 Y-chromosome
      haplotypes. CONCLUSIONS: These census figures are more than three times greater
      than a previous estimate based on an extrapolation from small-scale nest count
      surveys that tend to underestimate population size. The distribution of genotype
      clusters and Y-chromosome haplotypes together indicate the presence of numerous
      male philopatric chimpanzee communities throughout the corridor habitat. Our
      findings demonstrate that, despite extensive habitat loss and fragmentation,
      chimpanzees remain widely distributed and exhibit distinct community home ranges.
      Our results further imply that elusive and rare species may adapt to degraded
      habitats more successfully than previously believed. Their long-term persistence
      is unlikely, however, if protection is not afforded to them and habitat loss
      continues unabated.

PMID- 26303658
TI  - Rare SHANK2 variants in schizophrenia.

PMID- 26303657
TI  - Advancing breast cancer survivorship among African-American women.
AB  - Advances have occurred in breast cancer survivorship but, for many African
      American women, challenges and gaps in relevant information remain. This article
      identifies opportunities to address disparities in breast cancer survival and
      quality of life, and thereby to increase breast cancer survivorship among African
      American women. For breast cancer survivors, common side effects, lasting for
      long periods after cancer treatment, include fatigue, loss of strength,
      difficulty sleeping, and sexual dysfunction. For addressing physical and mental
      health concerns, a variety of interventions have been evaluated, including
      exercise and weight training, dietary interventions, yoga and mindfulness-based
      stress reduction, and support groups or group therapy. Obesity has been
      associated with breast cancer recurrence and poorer survival. Relative to white
      survivors, African-American breast cancer survivors are more likely to be obese
      and less likely to engage in physical activity, although exercise improves
      overall quality of life and cancer-related fatigue. Considerable information
      exists about the effectiveness of such interventions for alleviating distress and
      improving quality of life among breast cancer survivors, but few studies have
      focused specifically on African-American women with a breast cancer diagnosis.
      Studies have identified a number of personal factors that are associated with
      resilience, increased quality of life, and positive adaptation to a breast cancer
      diagnosis. There is a need for a better understanding of breast cancer
      survivorship among African-American women. Additional evaluations of
      interventions for improving the quality of life and survival of African-American
      breast cancer survivors are desirable. 

PMID- 26303659
TI  - Parental age, birth order and neurodevelopmental disorders.

PMID- 26303661
TI  - The role of SHANK2 rare variants in schizophrenia susceptibility.

PMID- 26303662
TI  - Common psychiatric disorders share the same genetic origin: a multivariate
      sibling study of the Swedish population.
AB  - Recent studies have shown that different mental-health problems appear to be
      partly influenced by the same set of genes, which can be summarized by a general
      genetic factor. To date, such studies have relied on surveys of community-based
      samples, which could introduce potential biases. The goal of this study was to
      examine whether a general genetic factor would still emerge when based on a
      different ascertainment method with different biases from previous studies. We
      targeted all adults in Sweden (n=3 475 112) using national registers and
      identified those who had received one or more psychiatric diagnoses after seeking
      or being forced into mental health care. In order to examine the genetic versus
      environmental etiology of the general factor, we examined whether participants'
      full- or half-siblings had also received diagnoses. We focused on eight major
      psychiatric disorders based on the International Classification of Diseases,
      including schizophrenia, schizoaffective disorder, bipolar disorder, depression,
      anxiety, attention-deficit/hyperactivity disorder, alcohol use disorder and drug
      abuse. In addition, we included convictions of violent crimes. Multivariate
      analyses demonstrated that a general genetic factor influenced all disorders and
      convictions of violent crimes, accounting for between 10% (attention
      deficit/hyperactivity disorder) and 36% (drug abuse) of the variance of the
      conditions. Thus, a general genetic factor of psychopathology emerges when based
      on both surveys as well as national registers, indicating that a set of
      pleiotropic genes influence a variety of psychiatric disorders. 

PMID- 26303660
TI  - CNS-specific regulatory elements in brain-derived HIV-1 strains affect responses
      to latency-reversing agents with implications for cure strategies.
AB  - Latency-reversing agents (LRAs), including histone deacetylase inhibitors
      (HDACi), are being investigated as a strategy to eliminate latency in HIV
      infected patients on suppressive antiretroviral therapy. The effectiveness of
      LRAs in activating latent infection in HIV strains derived from the central
      nervous system (CNS) is unknown. Here we show that CNS-derived HIV-1 strains
      possess polymorphisms within and surrounding the Sp transcription factor motifs
      in the long terminal repeat (LTR). These polymorphisms result in decreased
      ability of the transcription factor specificity protein 1 to bind CNS-derived
      LTRs, reducing the transcriptional activity of CNS-derived viruses. These
      mutations result in CNS-derived viruses being less responsive to activation by
      the HDACi panobinostat and romidepsin compared with lymphoid-derived viruses from
      the same subjects. Our findings suggest that HIV-1 strains residing in the CNS
      have unique transcriptional regulatory mechanisms, which impact the regulation of
      latency, the consideration of which is essential for the development of HIV-1
      eradication strategies. 

PMID- 26303666
TI  - How Effective Is First-Trimester Screening for Trisomy 21 Based on Ultrasound
      Only?
AB  - OBJECTIVE: To evaluate the most common first-trimester ultrasound features of
      fetuses with trisomy 21 (T21) and to examine the screening performance for Down
      syndrome (DS) using only ultrasound-based protocols. To investigate whether
      maternal age (MA) has an impact on the efficacy of the ultrasound-based screening
      methods. METHODS: In a prospective study, 6,265 patients were examined. Two
      ultrasound-based risk calculation protocols were applied: 'NT' (based on nuchal
      translucency) and 'NT+' (based on NT and secondary markers). RESULTS: A total of
      5,696 patients were enrolled for analysis; 84 subjects with T21 were identified.
      Combinations of abnormal ultrasound markers were observed in only 1.2% of euploid
      fetuses compared to 71.5% of fetuses with T21. Among 17.9% of DS cases with
      cardiac anomaly, 14.3% comprised atrioventricular septal defects. For a false
      positive rate of 3%, the detection rates of T21 were 73.8 and 91.7% for the 'NT'
      and 'NT+' protocols, respectively. The efficacy of both methods was affected by
      MA. CONCLUSIONS: Most of the fetuses with DS demonstrate a combination of
      ultrasound markers of aneuploidy in the first trimester. The 'NT+' protocol is
      efficient and provides comparable performance as a combined screening test. It is
      a valuable method, especially when the access to biochemical analysis is
      restricted.

PMID- 26303665
TI  - Electrical stimulation in the bed nucleus of the stria terminalis alleviates
      severe obsessive-compulsive disorder.
AB  - In 1998, we proposed deep brain stimulation as a last-resort treatment option for
      patients suffering from severe, treatment-resistant obsessive-compulsive disorder
      (OCD). Here, 24 OCD patients were included in a long-term follow-up study to
      evaluate the effects of electrical stimulation in the anterior limbs of the
      internal capsule (ALIC) and bed nucleus of the stria terminalis (BST). We find
      that electrical stimulation in the ALIC/BST area is safe and significantly
      decreases obsessions, compulsions, and associated anxiety and depressive
      symptoms, and improves global functioning in a blinded crossover trial (n=17),
      after 4 years (n=18), and at last follow-up (up to 171 months, n=24). Moreover,
      our data indicate that BST may be a better stimulation target compared with ALIC
      to alleviate OCD symptoms. We conclude that electrical stimulation in BST is a
      promising therapeutic option for otherwise treatment-resistant OCD patients.

PMID- 26303664
TI  - Phenome-wide analysis of genome-wide polygenic scores.
AB  - Genome-wide polygenic scores (GPS), which aggregate the effects of thousands of
      DNA variants from genome-wide association studies (GWAS), have the potential to
      make genetic predictions for individuals. We conducted a systematic investigation
      of associations between GPS and many behavioral traits, the behavioral phenome.
      For 3152 unrelated 16-year-old individuals representative of the United Kingdom,
      we created 13 GPS from the largest GWAS for psychiatric disorders (for example,
      schizophrenia, depression and dementia) and cognitive traits (for example,
      intelligence, educational attainment and intracranial volume). The behavioral
      phenome included 50 traits from the domains of psychopathology, personality,
      cognitive abilities and educational achievement. We examined phenome-wide
      profiles of associations for the entire distribution of each GPS and for the
      extremes of the GPS distributions. The cognitive GPS yielded stronger predictive
      power than the psychiatric GPS in our UK-representative sample of adolescents.
      For example, education GPS explained variation in adolescents' behavior problems
      (~0.6%) and in educational achievement (~2%) but psychiatric GPS were associated
      with neither. Despite the modest effect sizes of current GPS, quantile analyses
      illustrate the ability to stratify individuals by GPS and opportunities for
      research. For example, the highest and lowest septiles for the education GPS
      yielded a 0.5 s.d. difference in mean math grade and a 0.25 s.d. difference in
      mean behavior problems. We discuss the usefulness and limitations of GPS based on
      adult GWAS to predict genetic propensities earlier in development.

PMID- 26303663
TI  - SORL1 rare variants: a major risk factor for familial early-onset Alzheimer's
      disease.
AB  - The SORL1 protein plays a protective role against the secretion of the amyloid
      beta peptide, a key event in the pathogeny of Alzheimer's disease. We assessed
      the impact of SORL1 rare variants in early-onset Alzheimer's disease (EOAD) in a
      case-control setting. We conducted a whole exome analysis among 484 French EOAD
      patients and 498 ethnically matched controls. After collapsing rare variants
      (minor allele frequency <=1%), we detected an enrichment of disruptive and
      predicted damaging missense SORL1 variants in cases (odds radio (OR)=5.03, 95%
      confidence interval (CI)=(2.02-14.99), P=7.49.10(-5)). This enrichment was even
      stronger when restricting the analysis to the 205 cases with a positive family
      history (OR=8.86, 95% CI=(3.35-27.31), P=3.82.10(-7)). We conclude that predicted
      damaging rare SORL1 variants are a strong risk factor for EOAD and that the
      association signal is mainly driven by cases with positive family history.

PMID- 26303667
TI  - How glaucoma patient characteristics, self-efficacy and patient-provider
      communication are associated with eye drop technique.
AB  - OBJECTIVES: The objective of this study was to examine the extent to which
      patient characteristics, eye drop technique self-efficacy, and ophthalmologist
      patient communication about eye drop administration are associated with glaucoma
      patients' ability to instil a single drop, have the drop land in the eye, and
      avoid touching the applicator tip of the medication bottle to the eye or face
      while self-administering eye drops. METHODS: Glaucoma patients (n = 279) were
      recruited from six ophthalmology clinics. Medical visits were videotape-recorded.
      Afterwards, patients were interviewed and demonstrated administering an eye drop
      on a videotaped-recording. Generalized estimating equations were used to analyse
      the data. KEY FINDINGS: Ophthalmologists provided eye drop administration
      instruction to 40 patients. Patients with more years of education were
      significantly more likely to both instil a single drop (P = 0.017) and have the
      drop land in their eye (P = 0.017). Women were significantly more likely to touch
      the applicator tip to their eyes or face (P = 0.014). Patients with severe
      glaucoma (P = 0.016), women (P = 0.026), and patients who asked at least one eye
      drop administration question (P = 0.001) were significantly less likely to instil
      a single drop. Patients with arthritis were significantly less likely to have the
      drop land in their eye (P = 0.008). African American patients were significantly
      less likely to touch the applicator tip to their eyes or face (P = 0.008).
      CONCLUSIONS: Some glaucoma patients have a difficult time self-administering eye
      drops. As so few patients received eye drop administration instruction from their
      providers, there is an opportunity for pharmacists to complement care.

PMID- 26303669
TI  - Draft genome sequence of the denitrifying strain Kiloniella sp. P1-1 isolated
      from the gut microflora of Pacific white shrimp, Litopenaeus vannamei.
AB  - A denitrifying bacterium, Kiloniella sp. P1-1, was isolated from the intestinal
      tract contents of Pacific white shrimp (Litopenaeus vannamei) from the Taiwan
      Strait, China. Here we report the draft genome sequence of Kiloniella sp. P1-1,
      which comprised 4,312,146 bp in 85 contigs with a G+C content of 46.09%. Related
      genes involved in the denitrification process could be identified in this genome.
      The genome sequence of Kiloniella sp. P1-1 may provide insights into the
      mechanism of denitrification. 

PMID- 26303668
TI  - Multiple-clone infections of Plasmodium vivax: definition of a panel of markers
      for molecular epidemiology.
AB  - BACKGROUND: Plasmodium vivax infections commonly contain multiple genetically
      distinct parasite clones. The detection of multiple-clone infections depends on
      several factors, such as the accuracy of the genotyping method, and the type and
      number of the molecular markers analysed. Characterizing the multiplicity of
      infection has broad implications that range from population genetic studies of
      the parasite to malaria treatment and control. This study compared and evaluated
      the efficiency of neutral and non-neutral markers that are widely used in studies
      of molecular epidemiology to detect the multiplicity of P. vivax infection.
      METHODS: The performance of six markers was evaluated using 11 mixtures of DNA
      with well-defined proportions of two different parasite genotypes for each
      marker. These mixtures were generated by mixing cloned PCR products or patient
      derived genomic DNA. In addition, 51 samples of natural infections from the
      Brazil were genotyped for all markers. The PCR-capillary electrophoresis-based
      method was used to permit direct comparisons among the markers. The criteria for
      differentiating minor peaks from artifacts were also evaluated. RESULTS: The
      analysis of DNA mixtures showed that the tandem repeat MN21 and the polymorphic
      blocks 2 (msp1B2) and 10 (msp1B10) of merozoite surface protein-1 allowed for the
      estimation of the expected ratio of both alleles in the majority of preparations.
      Nevertheless, msp1B2 was not able to detect the majority of multiple-clone
      infections in field samples; it identified only 6 % of these infections. The
      merozoite surface protein-3 alpha and microsatellites (PvMS6 and PvMS7) did not
      accurately estimate the relative clonal proportions in artificial mixtures, but
      the microsatellites performed well in detecting natural multiple-clone
      infections. Notably, the use of a less stringent criterion to score rare alleles
      significantly increased the sensitivity of the detection of multi-clonal
      infections. CONCLUSIONS: Depending on the type of marker used, a considerable
      amplification bias was observed, which may have serious implications for the
      characterization of the complexity of a P. vivax infection. Based on the
      performance of markers in artificial mixtures of DNA and natural infections, a
      minimum panel of four genetic markers (PvMS6, PvMS7, MN21, and msp1B10) was
      defined, and these markers are highly informative regarding the genetic
      variability of P. vivax populations.

PMID- 26303670
TI  - Masculine discrepancy stress, substance use, assault and injury in a survey of US
      men.
AB  - To understand and ultimately prevent injury and behavioural health outcomes
      associated with masculinity, we assessed the influence of masculine discrepancy
      stress (stress that occurs when men perceive themselves as falling short of the
      traditional gender norms) on the propensity to engage in stereotypically
      masculine behaviours (eg, substance use, risk taking and violence) as a means of
      demonstrating masculinity. Six-hundred men from the USA were recruited via
      Amazon's Mechanical Turk (MTurk) online data collection site to complete surveys
      assessing self-perceptions of gender role discrepancy and consequent discrepancy
      stress, substance use/abuse, driving while intoxicated (DWI) and violent
      assaults. Negative binomial regression analyses indicated significant interactive
      effects wherein men high on gender role discrepancy and attendant discrepancy
      stress reported significantly more assaults with a weapon (B=1.01; SE=0.63;
      IRR=2.74; p=0.05) and assaults causing injury (B=1.01; SE=0.51; IRR=2.74;
      p<0.05). There was no association of discrepancy stress to substance abuse, but
      there was a protective effect of gender role discrepancy for DWI among men low on
      discrepancy stress (B=-1.19, SE=0.48; IRR=0.30; p=0.01). These findings suggest
      that gender role discrepancy and associated discrepancy stress, in particular,
      represent important injury risk factors and that prevention of discrepancy stress
      may prevent acts of violence with the greatest consequences and costs to the
      victim, offender and society.

PMID- 26303671
TI  - The choice of prior distribution for a covariance matrix in multivariate meta
      analysis: a simulation study.
AB  - Bayesian meta-analysis is an increasingly important component of clinical
      research, with multivariate meta-analysis a promising tool for studies with
      multiple endpoints. Model assumptions, including the choice of priors, are
      crucial aspects of multivariate Bayesian meta-analysis (MBMA) models. In a given
      model, two different prior distributions can lead to different inferences about a
      particular parameter. A simulation study was performed in which the impact of
      families of prior distributions for the covariance matrix of a multivariate
      normal random effects MBMA model was analyzed. Inferences about effect sizes were
      not particularly sensitive to prior choice, but the related covariance estimates
      were. A few families of prior distributions with small relative biases, tight
      mean squared errors, and close to nominal coverage for the effect size estimates
      were identified. Our results demonstrate the need for sensitivity analysis and
      suggest some guidelines for choosing prior distributions in this class of
      problems. The MBMA models proposed here are illustrated in a small meta-analysis
      example from the periodontal field and a medium meta-analysis from the study of
      stroke. Copyright (c) 2015 John Wiley & Sons, Ltd. 

PMID- 26303673
TI  - Hepatitis: A variant resulting in hypofunctional IRAK2 hampers spontaneous
      clearance of HCV.

PMID- 26303672
TI  - Quality of Life in the Chronic GVHD Consortium Cohort: Lessons Learned and the
      Long Road Ahead.
AB  - Patient-reported outcomes are receiving increased attention as the search for
      successful treatment agents of chronic graft versus host disease continues. There
      is currently an ongoing multicenter, prospective cohort study lead by the Chronic
      GVHD Consortium of patients with chronic graft versus host disease. This paper
      summarizes published findings to date reporting factors impacting quality of
      life, symptom burden, and physical functioning in this cohort. Middle age, versus
      younger or older age, is associated with worse quality of life, despite lower
      symptom burden. The presence of chronic graft versus host disease at study
      enrollment was associated with lower quality of life, and improvement in severity
      does not always change quality of life. Other factors negatively impacting
      quality of life include the presence of overlap syndrome, specific
      gastrointestinal and joint and fascia manifestations, and poorer functional
      status and exercise tolerance. Collecting valid and concise quality of life data
      is essential in developing treatment strategies for chronic graft versus host
      disease. 

PMID- 26303676
TI  - OD-seq: outlier detection in multiple sequence alignments.
AB  - BACKGROUND: Multiple sequence alignments (MSA) are widely used in sequence
      analysis for a variety of tasks. Outlier sequences can make downstream analyses
      unreliable or make the alignments less accurate while they are being constructed.
      This paper describes a simple method for automatically detecting outliers and
      accompanying software called OD-seq. It is based on finding sequences whose
      average distance to the rest of the sequences in a dataset, is anomalous.
      RESULTS: The software can take a MSA, distance matrix or set of unaligned
      sequences as input. Outlier sequences are found by examining the average distance
      of each sequence to the rest. Anomalous average distances are then found using
      the interquartile range of the distribution of average distances or by
      bootstrapping them. The complexity of any analysis of a distance matrix is
      normally at least O(N(2)) for N sequences. This is prohibitive for large N but is
      reduced here by using the mBed algorithm from Clustal Omega. This reduces the
      complexity to O(N log(N)) which makes even very large alignments easy to analyse
      on a single core. We tested the ability of OD-seq to detect outliers using
      artificial test cases of sequences from Pfam families, seeded with sequences from
      other Pfam families. Using a MSA as input, OD-seq is able to detect outliers with
      very high sensitivity and specificity. CONCLUSION: OD-seq is a practical and
      simple method to detect outliers in MSAs. It can also detect outliers in sets of
      unaligned sequences, but with reduced accuracy. For medium sized alignments, of a
      few thousand sequences, it can detect outliers in a few seconds. Software
      available as http://www.bioinf.ucd.ie/download/od-seq.tar.gz.

PMID- 26303674
TI  - Coeliac disease and autoimmune disease-genetic overlap and screening.
AB  - Coeliac disease is a treatable, gluten-induced disease that often occurs
      concurrently with other autoimmune diseases. In genetic studies since 2007, a
      partial genetic overlap between these diseases has been revealed and further
      insights into the pathophysiology of coeliac disease and autoimmunity have been
      gained. However, genetic screening is not sensitive and specific enough to
      accurately predict disease development. The current method to diagnose
      individuals with coeliac disease is serological testing for the presence of
      autoantibodies whilst the patient is on a regular, gluten-containing diet,
      followed by gastroduodenoscopy with duodenal biopsy. Serological test results can
      also predict the probability of coeliac disease development, even if
      asymptomatic. In patients with autoimmune diseases known to occur alongside
      coeliac disease (particularly type 1 diabetes mellitus or thyroid disorders),
      disease screening-and subsequent treatment if coeliac disease is detected-could
      have beneficial effects on progression or potential complications of both
      diseases, owing to the effectiveness of gluten-free dietary interventions in
      coeliac disease. However, whether diagnosis of coeliac disease and subsequent
      dietary treatment can prevent autoimmune diseases is debated. In this Review, the
      genetic and immunological features of coeliac disease, overlap with other
      autoimmune diseases and implications for current screening strategies will be
      discussed. 

PMID- 26303677
TI  - Imiquimod 3.75% in actinic keratosis: efficacy in patients with and without rest
      periods during treatment.

PMID- 26303678
TI  - Exercise Training Protects Against Acute Myocardial Infarction via Improving
      Myocardial Energy Metabolism and Mitochondrial Biogenesis.
AB  - BACKGROUND/AIMS: Acute myocardial infarction (AMI) represents a major cause of
      morbidity and mortality worldwide. Exercise has been proved to reduce myocardial
      ischemia-reperfusion (I/R) injury However it remains unclear whether, and (if so)
      how, exercise could protect against AMI. METHODS: Mice were trained using a 3
      week swimming protocol, and then subjected to left coronary artery (LCA)
      ligation, and finally sacrificed 24 h after AMI. Myocardial infarct size was
      examined with triphenyltetrazolium chloride staining. Cardiac apoptosis was
      determined by TUNEL staining. Mitochondria density was checked by Mito-Tracker
      immunofluorescent staining. Quantitative reverse transcription polymerase chain
      reactions and Western blotting were used to determine genes related to apoptosis,
      autophagy and myocardial energy metabolism. RESULTS: Exercise training reduces
      myocardial infarct size and abolishes AMI-induced autophagy and apoptosis. AMI
      leads to a shift from fatty acid to glucose metabolism in the myocardium with a
      downregulation of PPAR-alpha and PPAR-gamma. Also, AMI induces an adaptive
      increase of mitochondrial DNA replication and transcription in the acute phase of
      MI, accompanied by an activation of PGC-1alpha signaling. Exercise abolishes the
      derangement of myocardial glucose and lipid metabolism and further enhances the
      adaptive increase of mitochondrial biogenesis. CONCLUSION: Exercise training
      protects against AMI-induced acute cardiac injury through improving myocardial
      energy metabolism and enhancing the early adaptive change of mitochondrial
      biogenesis.

PMID- 26303679
TI  - Do Faith Communities Have a Role in Addressing Childhood Obesity?
AB  - OBJECTIVES: Pediatric obesity is a multifaceted phenomenon. A partnership with
      faith-based communities to address the issue has been suggested. The purpose of
      this study was to describe the cultural beliefs of faith community leaders
      regarding childhood obesity and to examine attitudes about their role in
      addressing the issue. DESIGN AND SAMPLE: A qualitative descriptive design
      informed by ethnographic methods and triangulation of multiple data sources was
      utilized to assess the cultural beliefs of faith community leaders. A purposive
      sample of 13 leaders (nine females, four males) from seven multicultural and
      multigenerational local faith communities participated in the study. No more than
      three participants from any one faith community were enrolled in the study.
      RESULTS: Twenty-first century lifestyle challenges, accountability of behaviors
      (a dichotomy that fluctuated between individual responsibility to community
      and/or social responsibility), and the need for intentionality emerged as themes
      from the data. CONCLUSIONS: Faith community leaders envisioned a role for faith
      communities in addressing childhood obesity. Findings support the ongoing
      development of population based health promotion programs through faith community
      engagement. The findings provide a foundation for nurses partnering with faith
      communities on health promotion programs targeting childhood obesity to address
      family health issues in a holistic way.

PMID- 26303675
TI  - Towards a systems view of IBS.
AB  - Despite an extensive body of reported information about peripheral and central
      mechanisms involved in the pathophysiology of IBS symptoms, no comprehensive
      disease model has emerged that would guide the development of novel, effective
      therapies. In this Review, we will first describe novel insights into some key
      components of brain-gut interactions, starting with the emerging findings of
      distinct functional and structural brain signatures of IBS. We will then point
      out emerging correlations between these brain networks and genomic,
      gastrointestinal, immune and gut-microbiome-related parameters. We will
      incorporate this new information, as well as the reported extensive literature on
      various peripheral mechanisms, into a systems-based disease model of IBS, and
      discuss the implications of such a model for improved understanding of the
      disorder, and for the development of more-effective treatment approaches in the
      future. 

PMID- 26303680
TI  - Alternate current biosusceptometry for the assessment of gastric motility after
      proximal gastrectomy in rats: a feasibility study.
AB  - BACKGROUND: This study proposes an experimental model to assess the consequences
      of gastric surgeries on gastric motility. We investigated the effects of proximal
      gastrectomy (PG) using a non-invasive technique (alternate current
      biosusceptometry [ACB]) on gastric contractility (GC), gastric emptying (GE), and
      orocecal transit (OCT) after the ingestion of liquids and solids in rats.
      METHODS: Twenty-four male rats were subjected to gastric motility assessment
      before and after the PG procedure. The GE and OCT results are expressed as the
      mean time of gastric emptying (MGET) and cecum arrival (MCAT). The GC recordings
      are presented as the frequency and amplitude of contractions. KEY RESULTS: Mean
      time of gastric emptying after solid meals were significantly different (p <
      0.001) between control and PG (113 +/- 5 to 99 +/- 6 min). Mean time of cecum
      arrival ranged from 265 +/- 9 to 223 +/- 11 min (p < 0.001) and 164 +/- 9 to 136
      +/- 17 min (p < 0.050) for solid and liquid meals, respectively. The assessment
      of GC showed that surgery decreased the phasic frequency (4.4 +/- 0.4 to 3.0 +/-
      1.1 cpm, p < 0.050) and increased the amplitude of contractions (3.6 +/- 2.7 to
      7.2 +/- 3.0 V/s, p < 0.050). No significant difference was found in tonic
      frequency. CONCLUSIONS & INFERENCES: The ACB system was able to assess GE, OCT,
      and GC in gastrectomized rats. Overall, PG accelerated GE and gastrointestinal
      transit, likely due to the increase in both intragastric pressure and amplitude
      contraction. Our data presented an efficient model to investigate functional
      consequences from gastric surgeries that will allow further studies involving
      different procedures.

PMID- 26303681
TI  - [Laparoscopic surgery for colorectal cancer: are we in the era of complete
      mesentery excision?].
AB  - Total mesorectal excision(TME) is widely adopted wordwide, while discrepancies
      exist between surgical, embryological and anatomical descriptions of complete
      mesocolic excision(CME). Technically, it is feasible to do CME laparoscopically,
      which also could achieve satisfactory pathological results. Although further long
      term outcomes of laparoscopic CME procedure should be concerned, the concept of
      complete mesenteric(both colon and rectum) excision is positive to the
      standardization and high quality of laparoscopic surgery for colorectal cancer.
      It may say that we are in the era of complete mesentery excision. 

PMID- 26303682
TI  - [Macro surgery: a merge of minimal invasive surgery, membrane anatomy, and
      industry].
AB  - Minimal invasive surgery (MIS), which is presented by laparoscopy, has developed
      for more than a quarter of century. More and more surgical operations can be
      finished by laparoscopy, not only for cholecystectomy, but also for some complex
      operations, even radical operation for gastrointestinal cancer, such as radical
      rectectomy, D3 colectomy, D2 gastrectomy. These operations have small incisions
      only, but with extensive injury and bleeding in the abdomen. Meanwhile, total
      mesorectal excision (TME) for rectal cancer and complete mesocolic excision (CME)
      for colon cancer have been proposed by surgeons in the field of open surgery.
      During those procedures, they suggested that it is very important to find out a
      "space", then expand it to a "holly plane", to achieve resection en bloc and less
      bleeding, namely "plane surgery". In fact, the "plane" is consisted of two
      membranes under laparoscopy, that is the membranes (fascia or serous) which come
      from the mesentery in broad sense(or tissue bloc) and its bed. Understanding of
      the membrane anatomy we proposed, which includes the mesentery in broad sense(or
      tissue bloc) and the mesentery bed, will help the surgeons identify the correct
      anatomy or plane intentionally or accurately, and perform operations more easily,
      more precisely with less bleeding, more radically and less side injury. However,
      It is not easy to identify the membrane anatomy by naked eyes or traditional
      laparoscopy. It is not only dependent on the development of knowledge of membrane
      anatomy, but also the instruments developed by industry. Now, it seems to become
      possible when industry of optic or glass developed some instruments, such as 3D
      laparoscopy, binocular loupe, which have the proper magnifying power and high
      density resolution, and can identify the membrane anatomy at macro level (not
      micro level). Wearing these instruments, based on the membrane anatomy(macro
      anatomy), the classical operations, which include traditional laparoscopy or open
      operation, progress from gross surgery to macro surgery. Macro surgery is more
      precise procedure and between the gross and micro surgery. The merge from
      clinical practice, basic science and industry results in macro surgery which will
      lead to a new surgery level. 

PMID- 26303683
TI  - [Is there a principle for digestive reconstruction after laparoscopic
      gastrectomy?].
AB  - The laparoscopic gastrectomy has been popularized world-wide, and more and more
      clinical trials have been designed and conducted. Nowadays, lymphadenectomy is
      not a technical problem for Chinese surgeons, and the type of digestive
      reconstruction is closely related with patients' quality of life. Besides the
      basic principle and indication, which both laparoscopic and open gastrectomy must
      follow, there are some technical characteristics of laparoscopic gastrectomy. So
      the maneuver and methods of reconstruction for laparoscopic gastrectomy is
      different from open surgery. Surgeons must carefully evaluate the clinical
      evidences and patient's conditions, individualize the optimal type of
      reconstruction, and conduct clinical trials. 

PMID- 26303684
TI  - [Laparoscopic surgery for low rectal cancer, intersphincteric resection, Miles or
      extralevator abdominoperineal excision].
AB  - Currently, the safety and efficiency of laparoscopic surgery for rectal cancer
      have been confirmed by large amount of evidences. Laparoscopic surgery has been
      commonly applied in the treatment for low rectal cancer. Sphincter preservation
      is a highly concerning issue for patients and surgeons during rectal cancer
      surgery. Sphincter-preserving surgery should be based on the R0 resection. The
      article reviews the application of laparoscopic surgery for low rectal cancer and
      the choice of operations for sphincter-preserving surgery. 

PMID- 26303685
TI  - [Current status and novel approach of robotic surgery for rectal cancer].
AB  - With the development of minimally invasive surgery, laparoscopic technique is now
      widely used in rectal surgery because of its advantages in terms of pain control,
      recovery of bowel function, length of hospital stay, short- and long-term
      outcomes. Total mesorectal excision(TME) is recommended as the standard procedure
      for rectal cancer. Laparoscopic TME, however, can be challenging due to its two
      dimensional vision, restricted instrument movements, and a prolonged learning
      curve. Robotic surgery overcomes these intrinsic limitations by superior three
      dimensional magnified optics, stable retraction platform, and 7 degrees of
      freedom of instrument movements, and offers an easier operation and shorter
      learning curve. This review summarizes the advantages as well as the current
      status of robotic rectal surgery, and explores the novel approach and new
      techniques with the related literature and the author's own experience. 

PMID- 26303686
TI  - [Quality control of laparoscopic colorectal surgery].
AB  - Total mesorectal excision(TME) has become the standardized modality in rectal
      cancer surgery. The strict quality control of surgery has been introduced. The
      improvement of surgery quality resulted in the decrease of local recurrence rate
      and the increase of survival rate. TME becomes the model that quality control of
      surgery improved outcomes. In view of this, in recent years, complete mesocolic
      excision (CME) and extralevator abdominoperineal excision (ELAPE) have been
      established as the corresponding standardized procedures, which shows the
      preliminary clinical effects. Utilization of laparoscopic surgery for management
      of colorectal cancer has been widely accepted. Laparoscopic TME and CME will
      further improve the overall outcomes of colorectal cancer. 

PMID- 26303687
TI  - [Dissection of splenic hilar lymph nodes for patients with gastric cancer: from
      the evidence-based view].
AB  - There are many controversial issues in the aspects of No.10 lymphadenectomy, such
      as the necessity of No.10 lymphadenectomy, the value of splenectomy, the most
      appropriate procedure and the safety as well as feasibility of laparoscopic or
      robotic No.10 lymphadenectomy. These issues will be discussed in this article
      from the evidence-based view. 

PMID- 26303688
TI  - [Evaluation of POSSUM scoring system in radical gastrectomy for gastric cancer
      patients].
AB  - OBJECTIVE: To assess the accuracy of POSSUM scoring system in predicting surgical
      risk in patients with gastric cancer, and provide a feasible reference to
      clinical decision. METHODS: Clinical data of 310 patients suffered from gastric
      cancer were analyzed retrospectively, including 278 cases in laparoscopic group
      and 32 cases in open group, between April 2009 and April 2014 in the department
      of minimally invasive gastrointestinal surgery, Peking University Cancer
      Hospital. Preoperative physiology score(PS), operative score(OS) and predictive
      morbidity rate(R1) were calculated according to POSSUM scoring system, which were
      used to assess the accuracy of R1 in open group. Two different scoring systems
      (R1traditional and R1modified according to adjustment of operative excision area)
      were applied in the laparoscopic group, and were compared for predicting the
      accuracy of R1 in the laparoscopic group. Besides, postoperative morbidities were
      compared between the two groups of patients with different preoperative
      physiological status(low risk group: PS<=20, high risk group: PS>=21). RESULTS:
      The predictive accuracy for open group patients were acceptable, and the ratio of
      expected and observed(E/O) was 1.2. In the laparoscopic group, the R1modified was
      29.1%, and observed morbidity was 23.4% with an E/O of 1.2. The R1modified was
      more accurate than R1traditional(38.5%, E/O traditional was 1.6). Both modified
      and traditional POSSUM scoring system predicted well in low risk patients in the
      laparoscopic and open group, and E/O was 1.0. However, it overestimated
      morbidities in median and high risk patients for both laparoscopic and open
      group. E/O was 1.6, and 1.9 in laparoscopic group, as well as 1.2 and 1.3 in open
      group. For patients in poor preoperative physiological status(PS>=21), the
      morbidity in laparoscopic group was lower than that in open group(27.3% vs. 5/7,
      P=0.020). CONCLUSIONS: Modified POSSUM scoring system predicted morbidity more
      accurately in the laparoscopic group than traditional system. As for patients in
      poor preoperative physiological status, laparoscopic assisted gastrectomy
      procedure might reduce postoperative morbidities.

PMID- 26303689
TI  - [Application of laparoscopy in gastrointestinal abdominal emergency operation for
      patients over 65 years old].
AB  - OBJECTIVE: To explore the clinical application of laparoscopy in gastrointestinal
      abdominal emergency operation for patients over 65 years old. METHODS: Clinical
      data of 138 cases (age>65 years) with acute abdomen undergoing laparoscopic
      surgery from January 2006 to June 2014 were analyzed retrospectively. Data of 170
      cases treated by laparotomy during the same period were enrolled as controls.
      RESULTS: The laparoscopy group and the laparotomy group showed statistically
      significant differences in blood loss [(107.1+/-47.7) ml vs. (163.6+/-106.5) ml,
      P=0.000], postoperative complications rate [2.9%(4/138) vs. 12.9%(22/170),
      P=0.022], hospital stay [(10.5+/-7.5) d vs. (16.5+/-9.9) d, P=0.044],
      postoperative ambulation time [(25.6+/-7.7) h vs. (33.2+/-5.6) h, P=0.020], and
      recovery time of postoperative gastrointestinal function [(36.9+/-9.1) h vs.
      (49.3+/-10.6) h, P=0.031]. Patients with acute appendicitis, upper digestive
      tract perforation and bowel obstruction in the laparoscopy group were superior to
      those in the laparotomy group in hospital stay, postoperative ambulation time,
      recovery time of postoperative gastrointestinal function and intraoperative blood
      loss(all P<0.01), while no significant differences in colon perforation and
      mesentery diseases were found in hospital stay, intraoperative blood loss and
      recovery time of postoperative gastrointestinal function between the two groups
      (all P>0.05). CONCLUSIONS: Compared with laparotomy, the laparoscopy offers the
      advantages of less trauma, faster recovery, shorter hospital stay, and lower
      postoperative complications rate for patients over 65 years with acute abdomen.

PMID- 26303690
TI  - [Endoscopic operation in the treatment of congenital duodenal membranous
      stenosis].
AB  - OBJECTIVE: To investigate the safety and efficacy of endoscopic duodenal
      valvectomy in the treatment of congenital duodenal membranous stenosis. METHODS:
      Clinical data of two children with congenital duodenal membranous stenosis
      undergoing endoscopic duodenal valvectomy in our institute within October 2014
      were analyzed retrospectively. This procedure was performed with Microknife XL
      and CRE balloon catheter through porous channel in the 9 mm flexible endoscope.
      RESULTS: The first case was a 2-year-old boy who received two endoscopic
      operations including duodenal diaphragm resection and duodenal dilatation because
      of incision retraction. The second case was a 19-month-old gril who received once
      endoscopic duodenal valvectomy. Duodenal obstruction of these two children was
      relieved after operation. Postoperative x-rays showed no perforation. They could
      play in the floor 6 hours after operation without any complains, drink water 12
      hours, take liquid diets 2 days and half solid food 3 days after operation.
      During follow-up a month after operation, the body weight gained was 1.5 and 1.0
      kg respectively, and the dietary components was significantly improved.
      CONCLUSION: Endoscopic duodenal valvectomy is feasible and effective in the
      treatment of congenital duodenal membranous stenosis.

PMID- 26303691
TI  - [Influence of visceral fat area on laparoscopic radical gastrectomy in patients
      with gastric carcinoma].
AB  - OBJECTIVE: To explore the influence of visceral fat area(VFA) on laparoscopic
      radical gastrectomy and short-term outcome in patients with gastric carcinoma.
      METHODS: Clinicopathological and imaging data of 202 patients with gastric cancer
      who were treated by laparoscopic radical gastrectomy in the Affiliated Hospital
      of Qingdao University from May 2011 to July 2014 were retrospectively analyzed.
      VFA of all the patients were measured by CT, of which more than 10 000 m(2) were
      found in 104 patients(VFA-L group), less than 10 000 m2 in other 98 patients (VFA
      S group). Intraoperative and postoperative outcomes were compared between the two
      groups. RESULTS: There were no differences in operation time, intraoperative
      blood loss and number of harvested lymph node between the two groups(all P>0.05).
      As compared to VFA-S group, VFA-L group had a higher incidence of conversion to
      open surgery[9.6%(10/104) vs. 2.0%(2/98), P=0.023], higher complication rate
      [22.1%(23/104) vs. 10.2%(10/98), P=0.003], longer postoperative fever time
      [(3.0+/-1.3) d vs. (2.4+/-1.1) d, P=0.000], total length of hospital stay
      [(18.6+/-11.8) d vs. (15.8+/-6.0) d, P=0.039]. There were no significant
      differences in first flatus passage time and total hospitalization costs between
      the two groups. CONCLUSION: Elevated VFA can raise the difficulty of laparoscopic
      radical gastrectomy, increase the risk of postoperative complication and prolong
      the postoperative recovery.

PMID- 26303692
TI  - [Clinical efficacy comparison between laparoscopic and open surgery in the
      treatment of gastric gastrointestinal stromal tumor].
AB  - OBJECTIVE: To compare the efficacy between laparoscopic and open surgery in the
      treatment of gastric gastrointestinal stromal tumor (gastric GIST), and to
      explore the feasibility and safety of laparoscopic resection for gastric GIST.
      METHODS: Clinical data of 226 gastric GIST patients confirmed by pathology with
      maximal tumor diameter less than 10 cm undergoing operation in our department
      from January 2002 to December 2013 were retrospectively analyzed. Among them, 158
      patients received laparoscopic surgery(laparoscopic group), and 68 open surgery
      (open group). Related indicators of clinical efficacy were compared between the
      two groups. Laparoscopic group patients were further divided into 4 groups
      according to chronological order, including 39 patients in group A, 39 in group
      B, 39 in group C and 41 in group D. Operating time was compared among 4 groups.
      RESULTS: Compared with the open group, laparoscopic group had shorter operation
      time [(138.8+/-69.2) min vs. (173.3+/-74.5) min, P=0.001], less intraoperative
      bleeding [30 ml vs. 125 ml, P=0.000], faster recovery to postoperative first
      flatus [(3.2+/-1.1) d vs. (3.8+/-1.1) d, P=0.000] and resumption of oral intake
      [(3.9+/-1.5) d vs. (4.7+/-1.5) d, P=0.000], and a shorter hospital stay [(8.1+/
      2.3) d vs. (10.0+/-2.6) d, P=0.001]. The operation time of laparoscopic group A,
      B, C and D was (181.0+/-81.2) min, (124.7+/-57.8) min, (126.9+/-67.9) min and
      (123.4+/-51.8) min respectively, and the difference was statistically
      significant(F=7.188, P=0.001). Median follow-up time of 226 patients was 32
      months(5 to 104 months). In laparoscopic group, 136 cases(86.1%) received follow
      up, and the 1-, 3-, and 5-year overall survival were 98.7%, 90.7% and 72.8%
      respectively. In the open group, 59 cases (86.8%) received follow-up, and the 1-,
      3-, and 5-year overall survival were 98.3%, 87.1% and 83.1%, respectively. The
      survival between two groups were not significantly different(P=0.164).
      CONCLUSIONS: Laparoscopic surgery removing gastric GIST with a maximal diameter
      of less than 10 cm is safe and feasible. The learning curve of laparoscopic
      gastric GIST surgery is about 40 cases.

PMID- 26303693
TI  - [Comparison of cranial-to-caudal medial versus traditional medial approach in
      laparoscopic right hemicolectomy: a case-control study].
AB  - OBJECTIVE: To compare the short-term efficacy of modified medial (M-M) with
      traditional medial(T-M) approach in laparoscopic right hemicolectomy(LRHC)/or
      extended laparoscopic right hemicolectomy(ELRHC) for right or hepatic flexure
      colon cancer. METHODS: A comparative, retrospective study was performed that
      included all the patients scheduled for LRHC or ELRHC for right or hepatic
      flexure colon cancer between June 2013 and August 2014. The following factors of
      two groups were assessed: patient characteristics, operative details, pathology,
      and surgical outcomes. RESULTS: A total of 99 patients were evaluated, including
      52 patients in the M-M group and 47 patients in the T-M group. Age, gender, body
      mass index, American Society of Anesthesiology(ASA) class, tumor location,
      diameter of tumor were not significantly different between the two groups. As
      compared to the T-M group, M-M group was associated with a significantly shorter
      operative time [(105.6+/-38.8) min vs. (138.2+/-39.5) min, P<0.05], less
      estimated mean blood loss[(38.4+/-12.4) ml vs. (87.2+/-24.6) ml, P<0.05] and
      lower intraoperative vascular damage rate [5.8%(3/52) vs. 25.5%(12/47), P<0.05].
      There were no significant differences between these two groups in terms of
      intraoperative complications, CME, conversion rate, number of harvested lymph
      node, postoperative ileus, hospital stay, wound, lung and urinary system
      infections. CONCLUSION: The use of M-M approach in laparoscopic right
      hemicolectomy provides short-term benefits in operative time and estimated blood
      loss compared with traditional medial approach.

PMID- 26303694
TI  - [Comparison of effects of hand-assisted laparoscopic and traditional laparoscopic
      right hemicolectomy on immune function].
AB  - OBJECTIVE: To compare the effects of hand-assisted laparoscopic and traditional
      laparoscopic right hemicolectomy on immune function. METHODS: From May 2010 to
      November 2013, 60 patients with right colon carcinoma were prospectively enrolled
      and randomly divided into hand-assisted laparoscopic surgery(HALS) group and
      traditional laparoscopic surgery(TLS) group with 30 cases in each group. CRP, IL
      6, CD3+, CD4+, CD8+ in the peripheral blood were measured and compared on the
      first day before operation, the first, third and fifth day after operation.
      RESULTS: CRP and IL-6 levels in two groups were significantly increased on the
      first, third and fifth days(P<0.01), and peaked on the third day after operation.
      Postoperative CRP and IL-6 levels were slightly higher in HALS group, but the
      difference was not statistically significant (P>0.05). CD3+ and CD4+ levels were
      significantly decreased on the first, third day after operation(P<0.05), and
      returned to preoperative levels on the fifth day after operation in both two
      groups, and the difference was not statistically significant(P>0.05). There was
      no significant difference in CD8+ between two groups either before surgery or
      after operation(P>0.05). CONCLUSION: Hand-assisted laparoscopic right
      hemicolectomy has the same effects of traditional laparoscopic right
      hemicolectomy in the relief of postoperative stress and the protection of immune
      function.

PMID- 26303695
TI  - [Clinical analysis of 11 cases undergoing transanal minimal invasive or combined
      laparoscopy total mesorectal excision for rectal cancer].
AB  - OBJECTIVE: To explore the feasibility and safety of transanal minimal invasive or
      combined laparoscopy total mesorectal excision. METHODS: Clinical data of 11
      cases with rectal cancer undergoing transanal total mesorectal excision(taTME) in
      our hospital between September 2014 and May 2015 were analyzed retrospectively.
      RESULTS: Among 11 patients, 3 underwent pure-taTME successfully without abdominal
      incision and ileostomy, whose operation time was 210, 230, 215 min respectively,
      while other 8 patients underwent laparoscopy-assisted taTME(hybrid-taTME) with
      operation time ranging from 150 to 290 (median 205) min. No patient was
      transferred to open operation, while larger tumors of two patients were removed
      from hypogastric 5 cm incision. Postoperative first day VAS score was 1 to
      3(2.0+/-0.6), the first flatus was 6 to 70(30.2+/-17.3) h, hospital stay was 4 to
      12(7.5+/-2.5) d, the blood loss was (104+/-127) ml and the liquid food intake was
      (28.3+/-6.3) h. Postoperative complications included 1 case of subcutaneous
      emphysema, 1 case of anastomotic stoma bleeding, 2 cases of dysuria, which were
      cured by conservative therapy. One patient developed rectovaginal fistula 20 days
      after operation and then underwent ileostomy. No relapse of tumor or death during
      follow-up. CONCLUSIONS: For suitable rectal cancer patients, taTME or hybrid
      taTME is feasible.

PMID- 26303696
TI  - [Effect of body mass index on postoperative short-term outcomes of laparoscopy
      radical gastrectomy: a meta-analysis].
AB  - OBJECTIVE: To evaluate the effect of body mass index (BMI) on postoperative short
      term outcomes of laparoscopy radical gastrectomy by meta-analysis. METHODS: A
      literature search was performed in PubMed, EMBASE, Cochrane Library databases,
      CNKI, and CBM, Wanfang database to screen clinical trials published before
      October 2014 that compared short-term outcomes between high BMI and low BMI
      patients undergoing laparoscopy radical gastrectomy. RevMan 5.2 was used to
      perform the meta-analysis. Begg's and Egger's tests were carried out with Stata
      12.0 software to evaluate the publication bias of enrolled literatures. RESULTS:
      Twelve studies involved a total of 4798 gastric cancer patients after laparoscopy
      radical gastrectomy. There were 1215 patients in high BMI group(BMI>=25 kg/m2)
      and 3583 patients in the low BMI group (BMI<25 kg/m2). Compared with the low BMI
      group, the high BMI group were associated with longer operation time (SMD=0.64,
      95%CI:0.35-0.93, P=0.000), more intraoperative blood loss(SMD=0.63, 95%CI:0.24
      1.03, P=0.002), less retrieved lymph nodes(SMD=-0.44, 95%CI:-0.72--0.17,
      P=0.002), and more postoperative complications(OR=1.44, 95%CI:1.19-1.74,
      P=0.000). There were no significant differences in postoperative hospital stay,
      the time to first flatus and initial complication(P>0.05). CONCLUSION: The higher
      BMI may result in a longer operation time, more intraoperative blood loss and a
      higher rate of postoperative complication after laparoscopy radical gastrectomy.

PMID- 26303697
TI  - [Gastrostomy in dogs with magnetic compression technique combined with
      endoscopy].
AB  - OBJECTIVE: To evaluate the feasibility of endoscopic gastrostomy combined with
      magnetic compression techniques in dogs. METHODS: The magnetic compression device
      consisted of a couple of cylindrical magnets with a hole in the center. A 14
      French gastric tube was inserted through the hole and fixed on the parent
      magnets. Four male mongrel dogs were selected randomly for the operation. The
      daughter magnet was placed into the dog's gastric body by a Zebra Guidewire under
      endoscopy, then a skin incision was performed on the left upper abdomen, through
      which the subcutaneous tissues and muscle were isolated up to the peritoneum. The
      parent magnet was placed on the surface of the peritoneum, which attracted the
      daughter magnet inside the gastric cavity automatically to compress the gastric
      wall and peritoneum. A needle was inserted through the gastric tube and punctured
      the tissue in the hole of the magnets repeatedly to form a fistula. After
      removing the needle, the gastrostomy was complete. The fistula was observed and
      its specimen was taken two weeks later under laparotomy. RESULTS: All the four
      operations were successfully performed, and the operation time was 11-15 minutes.
      The stoma was matured immediately, through which early enteral nutrition support
      was administered. The gastric wall and peritoneum were observed with well healing
      and no adhesion in the abdominal cavity under laparotomy two weeks after the
      operation. CONCLUSION: The gastrostomy performed by magnetic compression
      technique combined with endoscopy is convenient, minimally invasive and safe,
      which may be used in future clinical practice.

PMID- 26303698
TI  - [Formation mechanism of circulating tumor cells and progress of its application
      in I-III stage colorectal carcinoma].
AB  - It has been a problem in clinical practice that high recurrence and poor survival
      of patients with colorectal cancer undergoing surgery. As an easy-accessible,
      repetitive, non-invasive "liquid biopsy" technology, circulating tumor cells(CTC)
      can assist us in many fields, for instance, real-time monitoring tumor status and
      providing information about recurrence and prognosis of colorectal cancer. In
      this review, generation mechanism and relevant major regulation molecules of CTC
      will be elucidated, and principles, superiorities and inferiorities among
      different detection technologies were compared. Besides, clinical application and
      prognostic value of CTC in stage I-III colorectal caner were discussed, and the
      dilemma of low detection rate of CTC will be tried to solve as well.

PMID- 26303699
TI  - Sub ablative Er: YAG laser irradiation on surface roughness of eroded dental
      enamel.
AB  - OBJECTIVE: This study evaluated the effects of Er:YAG laser irradiation applied
      at varying pulse repetition rate on the surface roughness of eroded enamel.
      METHODS: Bovine enamel slabs (n = 10) were embedded in polyester resin, ground,
      and polished. To erosive challenges, specimens were immersed two times per day in
      20mL of concentrated orange juice (pH = 3.84) under agitation, during a two-day
      period. Specimens were randomly assigned to irradiation with the Er:YAG laser
      (focused mode, pulse energy of 60 mJ and energy density of 3.79 J/cm(2) )
      operating at 1, 2, 3, or 4 Hz. The control group was left nonirradiated. Surface
      roughness measurements were recorded post erosion-like formation and further
      erosive episodes by a profilometer and observed through atomic force microscopy
      (AFM). RESULTS: Analysis of variance revealed that the control group showed the
      lowest surface roughness, while laser-irradiated substrates did not differ from
      each other following post erosion-like lesion formation. According to analysis of
      covariance, at further erosive episodes, the control group demonstrated lower
      surface roughness (P > 0.05), than any of the irradiated groups (P < 0.05).
      CONCLUSIONS: The pulse repetition rate of the Er:YAG laser did not affect
      roughness of dental enamel eroded. The AFM images showed that the specimens
      irradiated by the Er:YAG laser at 1 Hz presented a less rough surface than those
      irradiated at 2, 3, and 4 Hz.

PMID- 26303701
TI  - Epidemiology of Neuroendocrine Tumors.
AB  - Formerly named carcinoids, neuroendocrine tumors originate from diffuse endocrine
      cells, can involve any part of the gastrointestinal tract, endocrine pancreas and
      bronchopulmonary (BP) tree, and have a wide range of malignant potential. This
      chapter summarizes the data available on the epidemiology of neuroendocrine
      neoplasia (NEN) from around the world, including the relative frequency according
      to organ of origin, annual incidence rates (IR) and trends in IR at the various
      anatomic sites, age and stage at presentation, racial and gender differences in
      IR and 5-year survival rates. Over time, changes have been made in the
      classification and registration of NEN, both in the same registry and across the
      globe, thus confounding the possibility to draw conclusions as to the true rise
      in IR of NEN that is observed all over the world. BP NEN has become the most
      common site in many western countries, while NEN of the rectum is more common in
      the Far East. In some countries, appendiceal NEN is the most common site in
      females. When compared to adenocarcinoma of the same location, the prognosis of
      NEN patients is better. Five-year survival rates are highest for NEN originating
      in the rectum and appendix, but lower in small intestinal and pancreatic NEN.
      Future research is needed to understand the contribution of genetic and
      environmental factors to NEN epidemiology.

PMID- 26303702
TI  - Biochemical Testing in Patients with Neuroendocrine Tumors.
AB  - Neuroendocrine tumors are usually slow-growing tumors. Many of these are capable
      of secreting peptide hormones or biogenic amines that may lead to endocrine
      syndromes. Nonfunctioning tumors can either secrete no hormones at all, or
      secrete hormones not giving rise to endocrine symptoms, such as chromogranin A,
      chromogranin B or pancreatic polypeptide. Chromogranin A is produced by the
      majority of endocrine tumors, both functioning and nonfunctioning, and is the
      best available marker for diagnosis, follow-up and treatment monitoring of
      patients with differentiated neuroendocrine tumors. Examples of endocrine
      syndromes are classical carcinoid syndrome caused by serotonin (measured in the
      urine as its metabolite 5-HIAA), insulinoma syndrome caused by insulin or
      proinsulin, Zollinger-Ellison syndrome resulting from gastrin secretion,
      glucagonoma syndrome caused by glucagon, WDHA syndrome caused by vasoactive
      intestinal peptide, or Cushing's syndrome resulting from ectopic production of
      adrenocorticotropic hormone or corticotropin-releasing hormone. In case there is
      uncertainty about the diagnosis, specific tests can be applied, such as the
      secretin test for diagnosis of gastrinomas and the 72-hour fast for diagnosis of
      an insulinoma. In patients with suspicion of an inherited syndrome, such as
      multiple endocrine neoplasia (MEN) 1 and MEN2 syndromes, genetic testing is
      indicated.

PMID- 26303700
TI  - Citalopram for the Treatment of Agitation in Alzheimer Dementia: Genetic
      Influences.
AB  - OBJECTIVE: To assess potential genetic influences on citalopram treatment
      efficacy for agitation in individuals with Alzheimer dementia (AD). Six
      functional genetic variants were studied in the following genes: serotonin
      receptor 2A (HTR2A-T102C), serotonin receptor 2C (HTR2C-Cys23Ser), serotonin
      transporter (5HTT-LPR), brain-derived neurotropic factor (BDNF-Val66Met),
      apolipoprotein E (epsilon2, epsilon3, epsilon4 variants), and cytochrome P450
      (CYP2C19). Treatment response by genotype was measured by (1) the agitation
      domain of the Neurobehavioral Rating Scale, (2) the modified Alzheimer Disease
      Cooperative Study-Clinical Global Impression of Change scale (mADCS-CGIC), (3)
      the agitation domain of the Neuropsychiatric Inventory (NPI), and (4) the Cohen
      Mansfield Agitation Inventory. METHOD: We utilized data from the Citalopram for
      Agitation in Alzheimer's Disease (CitAD) database. CitAD was a 9-week randomized,
      double-blind, placebo-controlled multicenter clinical trial showing significant
      improvement in agitation and caregiver distress in patients treated with
      citalopram. Proportional odds logistic regression and mixed effects models were
      used to examine the above-mentioned outcome measures. RESULTS: Significant
      interactions were noted on the NPI agitation domain for HTR2A (likelihood ratio
      [LR] = 6.19, df = 2, P = .04) and the mADCS-CGIC for HTR2C (LR = 4.33, df = 2, P
      = .02) over 9 weeks. DISCUSSION: Treatment outcomes in CitAD showed modest,
      although statistically significant, influence of genetic variation at HTR2A and
      HTR2C loci. Future studies should continue to examine the interaction of known
      genetic variants with antidepressant treatment in patients with AD having
      agitation.

PMID- 26303703
TI  - Clinical Syndromes Related to Gastrointestinal Neuroendocrine Neoplasms.
AB  - Neuroendocrine neoplasms (NENs) comprise a heterogeneous group of tumors derived
      from multipotent neuroendocrine cells that have the inherent ability to
      synthesize and secrete a variety of substances (peptides and amines). When these
      substances are bioactive, NENs can present with a related clinical syndrome
      (functioning NENs) and/or symptoms of mass effects (functioning and
      nonfunctioning NENs). NENs differ in their pathogenesis, clinical syndromes
      produced, aspects of biological behavior and response to certain antitumor
      treatment. The carcinoid syndrome (CS) is the clinical constellation of secretory
      diarrhea, flushing, wheezing and dyspnea as a result of serotonin production
      mainly from small intestinal NENs. Complications of CS are frequent and include
      extensive mesenteric fibrosis, carcinoid heart disease and the life-threatening
      carcinoid crisis. A variety of substances (mainly hormones) are produced from
      NENs originating from the pancreas associated with specific symptoms that can
      lead to their precise diagnosis. NENs may also secrete substances characteristic
      of other sites of origin and produce a variety of paraneoplastic syndromes and/or
      change their secretory status with time. Surgery remains the best option for
      complete tumor resection and symptom relief. Surgery may also be used when
      medical treatment fails to obtain control of the symptoms along with
      cytoreductive techniques. Somatostatin analogs (octreotide and lanreotide)
      constitute the backbone of medical treatment for the majority of functioning NENs
      as they can alleviate symptoms, stabilize tumor growth and improve the quality of
      life. Telotristat etiprate is a novel oral agent that inhibits tryptophan
      hydroxylase, the key enzyme responsible for serotonin production, and can improve
      the symptoms of CS. Nonspecific and supportive therapies are also used for
      refractory cases. In this chapter the clinical features of functioning NENs will
      be analyzed as well as aspects of their diagnosis based on secretory substances
      and treatment of the hormonal excess.

PMID- 26303704
TI  - Radiological Imaging: Computed Tomography, Magnetic Resonance Imaging and
      Ultrasonography.
AB  - Neuroendocrine tumor (NET) imaging is generally performed by a combination of
      radiological and functional methods. Conventional radiological imaging of
      morphology (anatomy) is usually performed by computed tomography (CT), magnetic
      resonance imaging (MRI) and ultrasound, whereas functional imaging of
      somatostatin receptor expression generally utilizes scintigraphy, but recently
      also positron emission tomography (PET). Because of the large variations in tumor
      characteristics (for example primary location, presence or absence of hormonal
      production, proliferation and metastatic spread) and disease presentation, the
      imaging requirements in different patients are very diverse. Imaging also needs
      to be adapted according to the imaging application in the individual patient
      (tumor localization, staging, detection of recurrent disease, monitoring of
      therapy). Familiarity with the contrast-enhancement technique for CT and MRI is
      important in the interpretation and understanding of the radiological findings.
      The choice of the optimal imaging techniques also needs to be considered in the
      light of the department's local availability and expertise. In this review,
      methodological aspects of radiological imaging are described, imaging
      requirements for various types of NETs are discussed, and typical image findings
      are illustrated.

PMID- 26303705
TI  - Nuclear Medicine Imaging of Neuroendocrine Tumors.
AB  - An important role is reserved for nuclear imaging techniques in the imaging of
      neuroendocrine tumors (NETs). Somatostatin receptor scintigraphy (SRS) with
      (111)In-DTPA-octreotide is currently the most important tracer in the diagnosis,
      staging and selection for peptide receptor radionuclide therapy (PRRT). In the
      past decade, different positron-emitting tomography (PET) tracers have been
      developed. The largest group is the (68)Gallium-labeled somatostatin analogs
      ((68)Ga-SSA). Several studies have demonstrated their superiority compared to SRS
      in sensitivity and specificity. Furthermore, patient comfort and effective dose
      are favorable for (68)Ga-SSA. Other PET targets like beta-[(11)C]-5-hydroxy-L
      tryptophan ((11)C-5-HTP) and 6-(18)F-L-3,4-dihydroxyphenylalanine ((18)F-DOPA)
      were developed recently. For insulinomas, glucagon-like peptide-1 receptor
      imaging is a promising new technique. The evaluation of response after PRRT and
      other therapies is a challenge. Currently, the official follow-up is performed
      with radiological imaging techniques. The role of nuclear medicine may increase
      with the newest tracers for PET. In this review, the different nuclear imaging
      techniques and tracers for the imaging of NETs will be discussed.

PMID- 26303706
TI  - Endoscopy and Endoscopic Ultrasound in Assessing and Managing Neuroendocrine
      Neoplasms.
AB  - Despite advances in radiological and metabolic imaging, standard axial endoscopy
      and endoscopic ultrasonography (EUS) still play a pivotal role in a number of
      neuroendocrine neoplasms (NENs) of the gastrointestinal and duodenopancreatic
      region. Upper gastrointestinal endoscopy is essential for the detection and
      characterization of NEN up to the angle of Treitz (esophageal, gastric and
      duodenal). Ileocolonoscopy allows the assessing and diagnosing of rectal, colonic
      and very occasionally distal ileal lesions. Endoscopic assessment is the mainstay
      for diagnosing gastric NENs associated with hypergastrinemia, but is also useful
      in detecting and diagnosing duodenal NENs (both functional and nonfunctional) and
      ampullary NENs. As rectal NENs are on the increase, standard colonoscopy (often
      combined with endorectal EUS) is also useful in detecting and treating small
      rectal NENs. EUS is the modality of choice for diagnosing pancreatic NENs and for
      locoregional staging of esophageal, gastric, duodenal, pancreatic and rectal
      NENs. This chapter will expand on the diagnostic and therapeutic role of
      endoscopy and EUS in the field of gastrointestinal and pancreatic NENs.

PMID- 26303707
TI  - Pathology: Classification and Immunoprofile.
AB  - The classification of neuroendocrine neoplasms (NENs) has been evolving steadily
      over the last decades. Important prognostic factors of NENs are their
      proliferative activity and presence/absence of necrosis. These factors are
      reported in NENs of all body sites; however, the terminology as well as the exact
      rules of classification differ according to the location of the primary tumor.
      Only in gastroenteropancreatic (GEP) NENs a formal grading is performed. This
      grading is based on proliferation assessed by the mitotic count and/or Ki-67
      proliferation index. In the lung, NEN grading is an intrinsic part of the tumor
      designation with typical carcinoids corresponding to neuroendocrine tumor (NET)
      G1 and atypical carcinoids to NET G2; however, the presence or absence of
      necrotic foci is as important as proliferation for the differentiation between
      typical and atypical carcinoids. Immunohistochemical markers can be used to
      demonstrate neuroendocrine differentiation. Synaptophysin and chromogranin A are,
      to date, the most reliable and most commonly used for this purpose. Beyond this,
      other markers can be helpful, for example in the situation of a NET metastasis of
      unknown primary, where a hormonal profile or a panel of transcription factors can
      give hints to the primary site. Many immunohistochemical markers have been shown
      to correlate with prognosis but are not used in clinical practice, for example
      cytokeratin 19 and KIT expression in pancreatic NETs. There is no predictive
      biomarker in use, with the exception of somatostatin receptor (SSTR) 2 expression
      for predicting the amenability of a tumor to in vivo SSTR targeting for imaging
      or therapy.

PMID- 26303708
TI  - Genetics and Epigenetics of Pancreatic Neuroendocrine Tumors and Pulmonary
      Carcinoids.
AB  - In this chapter, we give an overview of the genetic and epigenetic background of
      neuroendocrine tumors (NETs), in particular pancreatic and pulmonary NETs.
      Studying the mechanism of disease of the inherited syndromes that feature NETs
      has provided valuable insights that have revolutionized the therapeutic options
      for these tumor types: both inhibition of mTOR (mammalian target of rapamycin)
      signaling and inhibition of angiogenesis have become standard treatments.
      Although sporadic NETs harbor relatively few somatic gene mutations, these
      somatic mutations often affect genes that encode epigenetic regulators. Restoring
      the aberrant epigenetic characteristics may be an attractive approach for future
      treatment.

PMID- 26303709
TI  - Pancreatic Surgery.
AB  - Pancreatic neuroendocrine tumors (pNETs) are rare and clinically demanding
      diseases. They are clinically defined as functioning or nonfunctioning depending
      on the presence of a syndrome related to inappropriate hormone secretion.
      Functioning pNETs are often small in size and localization may be difficult also
      due to their possible extraduodenal-pancreatic origin in the jejunum, stomach,
      mesentery, spleen and ovaries. The improvement and the widespread use of cross
      sectional imaging techniques has significantly increased the detection of small,
      nonfunctioning pNETs. The European Neuroendocrine Tumor Society (ENETS)
      guidelines now suggest a 'wait and see' policy for these small, incidentally
      discovered tumors, which are smaller than 2 cm. On the other hand, surgery still
      always represents the treatment of choice for pNETs >2 cm and/or for symptoms. A
      large proportion of patients with pNETs have locally advanced disease at
      diagnosis. Radical surgery of pNETs includes both typical and atypical pancreatic
      resections. At diagnosis, between 25 and 93% of patients with pNETs have
      synchronous neuroendocrine tumor liver metastases. Radical resection of the
      primary tumor, associated with complete, eventually multistep, resection of the
      liver metastases, can be considered in selected cases. In recent years minimally
      invasive approaches, either laparoscopic or robotic, have played an increasing
      role in the treatment of pNETs.

PMID- 26303710
TI  - Gastrointestinal Surgery of Neuroendocrine Neoplasms.
AB  - Surgery is the only treatment that may cure the patient with
      gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) and should always be
      considered as the first-line treatment if radical resection can be achieved. Even
      in cases where radical surgery is not possible, palliative resection may be
      performed to reduce local or hormone-induced symptoms and to improve quality of
      life. The surgical procedures for GEP-NENs are accordingly described below. In
      most patients life-long follow-up is required, even following radical surgery, as
      recurrence may occur several years later.

PMID- 26303711
TI  - Transplantation and Debulking Procedures for Neuroendocrine Tumors.
AB  - An array of treatment modalities is currently available in the management of
      patients with neuroendocrine tumors (NETs). Complete resection of the primary
      tumor and all metastatic lesions represents the only approach possessing intent
      to cure. However, due to patients' disease frequently being at an advanced stage
      on initial diagnosis only a minority of individuals are candidates for radical
      procedures. Cytoreductive surgery (debulking) may potentially confer improvements
      in quality of life and prolong overall survival. In light of the recent
      introduction of effective nonsurgical treatment options, the indication for
      cytoreductive surgery needs to be carefully assessed. The presence of
      nonresectable liver metastases is not a contraindication for resection of the
      primary tumor including locoregional disease in small bowel NETs. Resection of
      primary pancreatic NETs in the setting of unresectable metastatic liver disease
      may have a beneficial effect on the prognosis of selected patients with a tumor
      requiring less aggressive local surgery. Liver transplantation presents a
      generally accepted approach in meticulously selected patients with unresectable
      liver metastases. Stringent and validated selection criteria are not available.
      While overall survival is satisfactory, high recurrence rates hinder outcomes and
      call for the development and implementation of neoadjuvant and adjuvant concepts.
      Advances in intestinal transplantation over time may justify consideration of an
      individual with advanced neuroendocrine tumor disease unresponsive to standard
      medical or surgical treatment.

PMID- 26303712
TI  - A 25-Year Experience of Gastroenteropancreatic Neuroendocrine Tumors and
      Somatostatin (Congeners) Analogs: From Symptom Control to Antineoplastic Therapy.
AB  - Radioimmunoassay technology was utilized in the discovery of somatostatin and was
      quickly brought into therapeutics; however, it took the development of
      somatostatin congeners to solve its limitations of a short half-life. Therapeutic
      medical control of hyperhormonal states such as acromegaly, carcinoid syndrome
      and VIPoma significantly advanced from a nonspecific approach to one that
      specifically and effectively targeted the underlying pathophysiology. Clinical
      care was transformed from nonspecific symptom control to one of a significant
      improvement in not only quality of life, but also quantity of life. These data
      submitted to US and European regulatory authorities for approval included many
      investigative sites with no uniform protocol and multiple investigational new
      drugs, and have not been previously published. This review includes the original
      data demonstrating the transformational impact this class of agents had on
      specific disease subsets resulting in regulatory approval 25 years ago.
      Autoradiography techniques using somatostatin resulted in identifying, localizing
      and characterizing its receptor subtypes. Translating in vitro data to in vivo
      resulted in scintigraphic whole body and SPECT scans with (111)In-pentetreotide
      and was incorporated into standard clinical care 20 years ago. (68)Ga-octreotide
      congeners using PET scanning offers a major imaging advance. Peptide receptor
      radiotherapy has evolved over the last 2 decades and utilizes several therapeutic
      isotopes, including (90)Y and (177)Lu.

PMID- 26303713
TI  - Medical Therapy of Pulmonary Neuroendocrine Neoplasms: Targeted, Symptomatic and
      Chemotherapy.
AB  - Whenever feasible, surgery represents the treatment of choice for pulmonary
      neuroendocrine neoplasms (NENs). In patients with hypersecreting tumors, wide
      metastatic spread or those not candidates for a surgical treatment, medical
      therapies may assure a control of the secretory pattern and slow the rate of
      tumor growth. No specific trials have been designed so far for pulmonary NENs and
      the first randomized trial entirely dedicated to thoracic NENs (the LUNA trial)
      is ongoing. International scientific society guidelines (ESMO and NANETS) and
      recommendations (ENETS) are therefore necessarily based on expert experience, on
      the subgroup analysis of large multicenter trials not focused on pulmonary NENs,
      and on the analysis of small retrospective series. Somatostatin analogs represent
      the therapy of choice in the presence of associated carcinoid syndrome and
      ectopic acromegaly and a reasonable first-line in slow-progressing tumors. Due to
      the low rate of proliferation, platinum-based chemotherapy is generally reserved
      to rapidly progressing tumors. Temozolomide alone or in association has shown
      activity in small retrospective series or monocentric trials - larger multicenter
      trials will better define its efficacy. Everolimus alone or in combination with
      somatostatin analogs has shown activity in the subgroup analysis of a large
      multicenter trial (RADIANT II). Many other drugs have shown activity in the
      preclinical models but, at the moment, no prospective and randomized data are
      available.

PMID- 26303714
TI  - Peptide Receptor Radionuclide Therapy of Neuroendocrine Tumors.
AB  - Peptide receptor radionuclide therapy (PRRT) has been a well-accepted and
      effective therapeutic modality for inoperable or metastatic
      gastroenteropancreatic, bronchopulmonary and other neuroendocrine tumors for
      almost 2 decades. In general, PRRT is well tolerated with moderate toxicity in
      the majority of patients if the necessary precautions, appropriate dosage and
      coadministration of amino acids are undertaken. The two most commonly used
      radiopeptides, (90)Y-octreotide and (177)Lu-octreotate, produce significant
      objective response rates, with impact on progression-free survival and overall
      survival. In addition, biochemical and symptomatic responses are commonly
      observed. A key issue is the need to establish randomized controlled trials to
      standardize the treatment and facilitate comparison with other therapeutic
      strategies available.

PMID- 26303715
TI  - Hormone and Receptor Candidates for Target and Biotherapy of Neuroendocrine
      Tumors.
AB  - Neuroendocrine tumors (NETs) produce various hormones and bioactive substances
      and are known to express a large variety of peptide hormone receptors. While
      these hormones and receptors play a role in the pathophysiology of this
      heterogeneous group of tumors, they also form an important target for treatment
      and diagnosis. One of the most well-known target receptors in NETs are
      somatostatin receptors. On the basis of the expression of functional somatostatin
      receptors on the cell surface of NET cells, somatostatin analogs have already
      been used for decades to control symptoms related to hormonal overproduction in
      patients with NETs. Recent placebo-controlled studies have also demonstrated a
      significant antitumor activity, both in functioning and nonfunctioning NETs.
      Moreover, other peptide hormone receptors (e.g. receptors for GLP-1, CCK, GRP,
      secretin and dopamine) can be expressed at a high density in NETs. As such, these
      classes of receptors may also form potential targets for diagnosis and treatment.
      Finally, in recent years novel biotherapies targeting several growth factor
      systems have been introduced in the treatment of patients with NETs and are being
      explored for their efficacy in this setting, either as monotherapy or in
      combination treatment. This chapter aims to give an overview on the above topic.

PMID- 26303716
TI  - The Role of Chemotherapy in Well-Differentiated Gastroenteropancreatic
      Neuroendocrine Tumors.
AB  - Even though the neuroendocrine tumor (NET) field has entered the era of 'targeted
      therapy', the role of cytotoxic chemotherapy continues to be debated. High
      response rates, ranging from 30 to 70% depending on the line of therapy, are
      consistently observed in the treatment of pancreatic NETs, with lesser evidence
      of activity in other foregut tumors. Activity in midgut carcinoid tumors appears
      to be negligible. Unfortunately, placebo-controlled randomized controlled trials
      using modern response criteria are lacking: the bulk of the literature consists
      of small phase II trials and retrospective series. There are also no completed
      trials comparing modern chemotherapy regimens, and therefore little data exist to
      favor the use of streptozocin- versus temozolomide- versus oxaliplatin-based
      therapies. Due to the absence of high-level evidence, it is difficult to generate
      data-based guidelines on the appropriate sequencing of cytotoxic drugs versus
      targeted agents. Although conventional wisdom holds that targeted agents such as
      everolimus or sunitinib are more tolerable than cytotoxic drugs, there is no
      evidence to support this perception. As a general principle, chemotherapy may be
      more appropriate as early-line therapy in patients with bulky and/or symptomatic
      and/or rapidly progressive tumors, particularly of pancreatic origin. In patients
      with low-volume disease or slow-growing tumors, noncytotoxic drugs may be
      preferable in early lines of therapy, reserving chemotherapy for the salvage
      setting. Validation of predictive factors is imperative in order to appropriately
      match patients with optimal treatment. Methyl-guanine-methyl-transferase (MGMT)
      deficiency is likely to be a positive predictive factor for alkylating agents,
      but needs to be evaluated prospectively. It is also unclear whether
      immunostaining for MGMT expression, which can be somewhat subjective, is superior
      to PCR-based techniques, which assess MGMT methylation status. Other basic
      predictive factors, such as ki-67 index, need to be evaluated in prospective
      clinical trials. It will also be important to evaluate whether newly discovered
      mutations in pancreatic NETs, such as DAXX/ATRX, are associated with response to
      chemotherapy.

PMID- 26303717
TI  - Other Novel Therapies: Biomarkers, microRNAs and microRNA Inhibitors, DNA
      Methylation, Epigenetics, Immunotherapy and Virotherapy.
AB  - Neuroendocrine tumors (NETs) consist of heterogeneous neoplasms. The
      neuroendocrine cells of the human body are confined to certain organs, such as
      the thyroid, pancreas and adrenals, or they are dispersed throughout the body in
      the respiratory tract and in the intestinal mucosa. The cells belong to the
      diffuse endocrine cell system, share a neuroendocrine phenotype, and accumulate
      precursor molecules which are then processed into hormones, peptides or amines.
      The tightly controlled release on stimulation is either to the blood stream or
      adjacent cells or neurons. Neuroendocrine cells regulate various processes in the
      human body, such as gastrointestinal secretion, blood pressure and response to
      stress. NETs present a wide spectrum of malignant diseases from rather benign to
      very malignant and lethal variants. NETs may occur in any organ, but are mainly
      detected in the gastroenteropancreatic system and in the lungs. The understanding
      of NET biology and treatments has changed dramatically during the last decade.
      Today, the main problems that clinicians and translational scientists face in
      overcoming these malignancies relate to various aspects within the molecular
      pathogenesis of NETs. This chapter focuses on the importance of novel biomarkers:
      microRNA and microRNA inhibitors; DNA methylation and epigenetics, and
      immunotherapy and virotherapy to develop novel treatments for NETs.

PMID- 26303718
TI  - Clonal dissemination of multilocus sequence type ST15 KPC-2-producing Klebsiella
      pneumoniae in Bulgaria.
AB  - A total of 36 consecutive clinical and two fecal-screening carbapenem-resistant
      Klebsiella pneumoniae isolates from two Bulgarian university hospitals (Varna and
      Pleven) were investigated. Susceptibility testing, conjugation experiments, and
      plasmid replicon typing were carried out. Beta-lactamases were characterized by
      isoelectric focusing, PCR, and sequencing. Clonal relatedness was investigated by
      RAPD and multilocus sequence typing (MLST). Most of the isolates demonstrated
      multidrug resistance profile. Amikacin and tigecycline retained good activity
      with susceptibility rates of 95 and 87%, respectively. The resistance rate to
      colistin was 63%. Six RAPD- and MLST-types were identified: the dominating MLST
      type was ST15 (27 isolates), followed by ST76 (six isolates), and ST1350 (two
      isolates). ST101, ST258, and ST151 were detected once. All except one of the K.
      pneumoniae produced KPC-2, mostly in combination with CTX-M-15, while for one
      isolate (ST101) the enzymes OXA-48 and CTX-M-14 were found. All KPC-2-producing
      transconjugants revealed the presence of IncFII plasmid. The OXA-48- and CTX-M-14
      producing isolate showed the presence of L/M replicon type. The dissemination of
      KPC-2-producing K.pneumoniae in Bulgaria is mainly due to the sustained spread of
      successful ST15 clone and to a lesser extent of ST76 clone. This is the first
      report of OXA-48 producing ST101 K. pneumoniae in Bulgaria. 

PMID- 26303719
TI  - Evaluation of apparent diffusion coefficient and MR volumetry as independent
      associative factors for extra-prostatic extension (EPE) in prostatic carcinoma.
AB  - BACKGROUND: To assess mean apparent diffusion coefficient (ADC) and MR-derived
      tumor volume (Vt) as associative factors for extra-prostatic extension (EPE) in
      prostate cancer (PCa). METHODS: With institutional review board approval, 73
      consecutive patients diagnosed with PCa at trans-rectal ultrasound biopsy
      underwent preoperative multi-parametric (T2W+DWI+DCE) 3 Tesla MRI before radical
      prostatectomy between 2012 and 2014; 52% (38/73) patients had EPE. Clinical
      parameters including: age, prostate serum antigen (PSA), digital rectal
      examination (DRE) and percentage positive cores (PPC) were recorded. Two blinded
      radiologists subjectively evaluated for EPE using PI-RADS with T2W-MRI. A third
      blinded radiologist recorded: mean ADC (mm(2) /s) of tumor and tumor volume on
      ADC and T2W (derived from planar volumetry). VtMAX (the largest volume on ADC or
      T2W) was documented. Multivariate and receiver operator characteristic analyses
      were performed. RESULTS: There were no significant differences in age, DRE, or
      Gleason score between groups (P = 0.52, 0.06, 0.61, 0.36). PSA approached
      significance being higher with EPE (12.9 +/- 12.6 versus 8.2 +/- 7.4; P = 0.06).
      PPC was higher with EPE (60.9 +/- 21.9% versus 38.3 +/- 21.6%; P < 0.01) with an
      area under the curve (AUC) of 0.78 and sensitivity/specificity = 75.7/75% when
      PPC >= 45%. AUC for T2W-MRI was 0.46-0.51 with sensitivity/specificity = 40.0
      42.9/48.6-57.1% (R1, R2). Inter-observer agreement was fair, k = 0.39. There was
      no difference in mean ADC between groups (0.89 +/- 0.25 versus 0.88 +/- 0.19
      [EPE] mm(2) /s), P = 0.70. T2W-Vt, ADC-Vt, and VtMAX were larger with EPE (5.1 +/
      7.4, 5.8 +/- 6.5, 6.3 +/- 7.4 cm(3) versus 1.6 +/- 1.8, 1.8 +/- 1.3, 2.1 +/-
      1.8), P < 0.01. VtMAX AUC was 0.77 with sensitivity/specificity = 78.4/73.5% when
      VtMAX  >= 2.1 cm(3) which outperformed all other parameters (P > 0.05) except PPC
      (P = 0.6) for the diagnosis EPE. CONCLUSION: MR volumetry and percentage of
      positive core biopsies are associated with EPE; whereas, in this study, other
      clinical and MR parameters including mean ADC and subjective T2W-MR analysis were
      not useful for assessment of EPE.

PMID- 26303720
TI  - MYSTERIES OF THE HUMAN FETUS REVEALED.
AB  - The impressive program of research from the DiPietro laboratory succeeds in its
      aim to document the ontogeny of human fetal neurobehavioral development. From
      studies of great depth and breadth, and wielding creative methods of assessment,
      DiPietro et al. open a window into the largely inaccessible developing human
      fetal brain. This commentary, with reference to the seminal cardiovascular
      studies of the Laceys, supports the measures of the fetal heart to index fetal
      well-being and to provide evidence of stimulus processing. A separate case is
      made that the DiPietro program provides unique and invaluable information for
      assessing the influential Developmental Origins of Health and Disease or Fetal
      Programming Models. The goal of these models, to predict or understand the
      influences of early experience or response patterns on later postnatal life, is
      identical to the ultimate goal of the DiPietro program. Because human fetal
      behavior is uncontaminated by socialization or parenting or peers, it may be the
      best reflection of fetal exposures. The remarkable neurobehavioral profiles
      generated by the DiPietro program can make a critical contribution to the Fetal
      Programming Model in terms of sensitive and critical periods of nervous system
      vulnerability and to specify gestational periods of neurobehavioral risk. 

PMID- 26303721
TI  - High density linkage mapping of genomic and transcriptomic SNPs for synteny
      analysis and anchoring the genome sequence of chickpea.
AB  - This study presents genome-wide discovery of SNPs through next generation
      sequencing of the genome of Cicer reticulatum. Mapping of the C. reticulatum
      sequenced reads onto the draft genome assembly of C. arietinum (desi chickpea)
      resulted in identification of 842,104 genomic SNPs which were utilized along with
      an additional 36,446 genic SNPs identified from transcriptome sequences of the
      aforementioned varieties. Two new chickpea Oligo Pool All (OPAs) each having
      3,072 SNPs were designed and utilized for SNP genotyping of 129 Recombinant
      Inbred Lines (RILs). Using Illumina GoldenGate Technology genotyping data of
      5,041 SNPs were generated and combined with the 1,673 marker data from previously
      published studies, to generate a high resolution linkage map. The map comprised
      of 6698 markers distributed on eight linkage groups spanning 1083.93 cM with an
      average inter-marker distance of 0.16 cM. Utility of the present map was
      demonstrated for improving the anchoring of the earlier reported draft genome
      sequence of desi chickpea by ~30% and that of kabuli chickpea by 18%. The genetic
      map reported in this study represents the most dense linkage map of chickpea ,
      with the potential to facilitate efficient anchoring of the draft genome
      sequences of desi as well as kabuli chickpea varieties. 

PMID- 26303722
TI  - Pancreatic atrophy after allogeneic peripheral blood stem cell transplantation.

PMID- 26303723
TI  - Blood conservation: Why aren't we doing this for everyone?

PMID- 26303724
TI  - Technological innovation in cardiothoracic surgery: A pragmatist's approach.

PMID- 26303726
TI  - The safety of postnatal transport of newborns prenatally diagnosed  with duct
      dependent congenital heart disease.
AB  - OBJECTIVE: Critical congenital heart disease is increasingly recognized
      prenatally. Following the diagnosis, families are advised to deliver in a
      facility where neonatal cardiac interventions are available. We studied the
      safety of transport of neonates who had been prenatally diagnosed with duct
      dependent congenital heart lesions. METHODS: We performed a retrospective chart
      review of all fetuses diagnosed with duct-dependent congenital heart disease in
      our fetal program between 2007 and 2011. Demographic data, dose of prostaglandin
      infusion, respiratory status, blood gas data, as well as complications of the
      transport were collected. RESULTS: Twenty-nine neonates qualified for inclusion
      in the study. Ten were intubated (7 electively) prior to the transport. One of
      these required intervention for desaturation during the transport. One of the 19
      unintubated patients required emergent intubation during the transport. Thus, the
      overall rate of incidents was 6.9%. All 4 patients who developed apnea requiring
      intubation did so within 1 h of starting prostaglandin. CONCLUSIONS: Elective
      postnatal transport of neonates prenatally diagnosed with duct-dependent
      congenital heart lesions is safe. Prophylactic intubation of these infants may
      not be necessary. It would be advantageous to schedule the elective transport an
      hour after starting prostaglandin or later.

PMID- 26303725
TI  - Correlation between MUCT imaging, histology and functional capacity of the
      osteoarthritic knee in the rat model of osteoarthritis.
AB  - BACKGROUND: To acquire the most meaningful understanding of human arthritis, it
      is essential to select the disease model and methodology translatable to human
      conditions. The primary objective of this study was to evaluate a number of
      analytic techniques and biomarkers for their ability to accurately gauge bone and
      cartilage morphology and metabolism in the medial meniscal tear (MMT) model of
      osteoarthritis (OA). METHODS: MMT surgery was performed in rats to induce OA. A
      dynamic weight bearing system (DWB) system was deployed to evaluate the weight
      bearing capacity of the front and hind legs in rats. At the end of a 10-week
      study cartilage pathology was evaluated by micro computed tomography (MUCT),
      contrast enhanced MUCT (EPIC MUCT) imaging and traditional histology. Bone tissue
      was evaluated at the tibial metaphysis and epiphysis, including the subchondral
      bone. Histological techniques and dynamic histomorphometry were used to evaluate
      cartilage morphology and bone mineralization. RESULTS: The study results showed a
      negative impact of MMT surgery on the weight-bearing capacity of the operated
      limb. Surgery caused severe and extensive deterioration of the articular
      cartilage at the medial tibial plateau, as evidenced by elevated CTX-II in serum,
      EPIC MUCT and histology. Bone analysis by MUCT showed thickening of the
      subchondral bone beneath the damaged cartilage, loss of cancellous bone at the
      metaphysis and active osteophyte formation. CONCLUSIONS: The study emphasizes the
      need for using various methodologies that complement each other to provide a
      comprehensive understanding of the pathophysiology of OA at the organ, tissue and
      cellular levels. Results from this study suggest that use of histology, MUCT and
      EPIC MUCT, and functional DWB tests provide powerful combination to fully assess
      the key aspects of OA and enhance data interpretation.

PMID- 26303727
TI  - Gastroenterological Surgery: Stomach.

PMID- 26303728
TI  - Gastroenterological Surgery: Pancreas.

PMID- 26303729
TI  - General Gastroenterological Surgery: Spleen.

PMID- 26303730
TI  - Gastroenterological Surgery: Large intestine.

PMID- 26303731
TI  - Video-assisted thoracoscopic esophagectomy in the left lateral decubitus position
      in an esophageal cancer patient with pectus excavatum.
AB  - During thoracic cavity operations, it is difficult to obtain sufficient working
      space and good operative field visibility in patients with pectus excavatum
      because the space between the vertebral bodies and sternum is very narrow. Here,
      we report the successful treatment of esophageal cancer in a patient with pectus
      excavatum. A 77-year-old man with esophageal cancer was referred to our hospital
      for further treatment. He was diagnosed with multiple early esophageal squamous
      cell carcinomas. The patient had pectus excavatum, but because it was
      asymptomatic, a video-assisted thoracoscopic radical esophagectomy in the left
      lateral decubitus position without pectus excavatum repair was selected. Despite
      the patient's unusual anatomy, video-assisted thoracoscopic esophagectomy in the
      left decubitus position allowed for good operative field visibility, as the
      videoscope was inserted from the side of the diaphragm. This operative procedure
      is useful in patients with esophageal cancer who also have pectus excavatum. To
      the best of our knowledge, this is the second report of video-assisted
      thoracoscopic esophagectomy in an esophageal cancer patient with pectus
      excavatum. 

PMID- 26303732
TI  - Appendiceal submucosal mass as presentation of intestinal endometriosis.
AB  - Submucosal lesions are mass-like protuberances into the gastrointestinal lumen
      covered by normal mucosa. Making a definitive diagnosis is difficult because of
      the number of benign and malignant lesions and extrinsic compression. Here we
      report the case of a 42-year-old woman referred for colon polypectomy.
      Colonoscopy revealed a polypoid formation with externalization from the
      appendicular orifice covered by normal mucosa and another formation at the
      sigmoid colon. The histopathology of both lesions was normal. Endoscopic
      ultrasound showed a hypoechoic lesion that was slightly heterogeneous in the
      fourth layer, and CT colonography confirmed the findings. Surgical therapy with
      ileocolic resection and resection of the sigmoid lesion was performed. Surgical
      specimens revealed an appendicular intussusception by endometriosis and
      endometrial foci in the sigmoid. Intestinal endometriosis may have several
      presentations, but it should always be considered in the differential diagnosis
      of a submucosal lesion in the colon. 

PMID- 26303733
TI  - Laparoscopic surgery for sigmoidocutaneous fistula due to diverticulitis: A case
      report.
AB  - Sigmoidocutaneous fistulas due to sigmoid colon diverticulitis are very rare.
      Here we report a case in which laparoscopic sigmoidectomy was used to
      successfully treat a sigmoidocutaneous fistula due to diverticulitis. A 41-year
      old man was admitted to our hospital because of redness and swelling of the left
      inguinal skin. Enhanced abdominal CT revealed a subcutaneous abscess in the left
      lower abdomen. Percutaneous drainage was performed, and fistulography revealed a
      fistula between the sigmoid colon and left inguinal skin. Therefore, a
      sigmoidocutaneous fistula was diagnosed, and laparoscopic sigmoidectomy and
      fistulectomy were performed. The sigmoid colon had several diverticula, and a
      pathological examination revealed that the sigmoidocutaneous fistula was due to
      diverticulitis. The postoperative course was uneventful, and the patient was
      discharged on postoperative day 8. In cases of sigmoidocutaneous fistula,
      laparoscopic treatment can be safely performed. 

PMID- 26303734
TI  - Laparoscopic anterior pelvic exenteration for locoregionally advanced rectal
      cancer directly invading the urinary bladder: A case report of low anterior
      resection with en bloc cystectomy for sphincter preservation.
AB  - Laparoscopic multi-visceral resection in patients with T4 colorectal cancer
      remains controversial. A 73-year-old man was admitted to the hospital for
      rectosigmoid cancer directly invading the urinary bladder trigone without distant
      metastasis. We successfully performed complete resection by laparoscopic anterior
      pelvic exenteration while preserving the anus. After laparoscopic mobilization of
      the rectum, urinary bladder, and prostate, the urethra and urethral catheter were
      dissected to reveal the lower rectum. By pulling the urethral catheter toward the
      head, the prostate was excised retrogradely from the lower rectum anterior wall.
      The lower rectum was resected and anastomosed by the double stapling technique
      with a safe distal margin from the tumor. Pathological findings of the resected
      specimen indicated no residual tumor in the surgical margin. There was no
      evidence of recurrence 34 months after surgery. En bloc, R0, laparoscopic
      anterior pelvic exenteration for T4 rectal cancer is feasible. However, further
      studies with long-term follow-up are required to resolve oncological outcomes. 

PMID- 26303735
TI  - Single-incision cholecystectomy in a patient with situs inversus totalis
      presenting with cholelithiasis: A case report.
AB  - Laparoscopic cholecystectomy has become the gold standard for the treatment of
      cholelithiasis, and many reports of single-incision laparoscopic cholecystectomy
      have been published in the past few years. Situs inversus totalis is a very rare
      condition, but the variant anatomy should not preclude a minimally invasive
      approach to surgery. We report a case of successful single-port laparoscopic
      cholecystectomy in a patient with situs inversus totalis, describe the technical
      advantages, and review the literature. 

PMID- 26303736
TI  - Urgent laparoscopic mesh splenopexy for torsion of wandering spleen and distal
      pancreas: A case report.
AB  - Wandering spleen is a condition in which an incomplete fusion of the splenic
      ligaments allows the spleen to move within the abdomen, predisposing it to
      splenic torsion along its vascular pedicle. Torsion of a wandering spleen is an
      uncommon occurrence, especially in children, and associated torsion of the distal
      pancreas is even more unusual, with only four cases having been reported in
      adults. Non-specific clinical presentation makes radiologic evaluation essential
      in order to obtain a diagnosis and to send the patient for early surgery before
      life-threatening complications arise. Here we present a rare case of torsion of
      wandering spleen together with volvulus of the distal pancreas in a 13-year-old
      girl. In this case, prompt radiological assessment allowed for an early
      diagnosis, and the patient was successfully treated with urgent laparoscopic
      derotation of both the spleen and the distal pancreas as well as mesh splenopexy.
      To the best of our knowledge, this procedure has never been described in a
      pediatric setting. 

PMID- 26303737
TI  - Laparoscopic repair of a Bochdalek hernia in an adult woman.
AB  - Bochdalek hernia (BH) is a congenital defect of the diaphragm that usually
      presents in the neonatal period with life threatening cardiorespiratory distress.
      It is rare for BH to remain silent until adulthood. A 51-year-old woman presented
      with progressive dyspnea and abdominal symptoms, but without a history of trauma.
      The diagnosis of BH was made based on chest X-ray and CT. The hernia was repaired
      by the laparoscopic technique, and the patient made an uneventful recovery. This
      report validates the feasibility of laparoscopic repair of BH in an adult, which
      should be within the capability of an advanced laparoscopic surgeon. 

PMID- 26303738
TI  - Laparoscopic Toupet Fundoplication using an Air Seal Intelligent Flow System and
      Anchor Port in a 1.8-kg infant: A Technical Report.
AB  - INTRODUCTION: We report a case of a 1.8-kg infant who had laparoscopic Toupet
      fundoplication (LTF) using the AirSeal Intelligent Flow System and Anchor Port
      (AP). MATERIALS AND SURGICAL TECHNIQUE: Our case had severe gastroesophageal
      reflux in association with genetic and cardiac anomalies. Despite the patient
      being continuously fed, persistent vomiting caused failure to thrive, and LTF was
      performed at 4 months of age when he weighed 1.8 kg. The AirSeal Intelligent Flow
      System is a novel laparoscopic CO2 insufflation system that improves the visual
      field by constantly evacuating smoke and providing a more stable
      pneumoperitoneum. The AP is a recently developed, stretchable, elastomeric, low
      profile cannula. Three 5-mm AP were inserted: one subumbilically for the scope
      and one in both the right and left upper abdomen for the surgeon. A 5-mm AirSeal
      trocar was inserted in the left lower abdomen for the assistant. The
      gastrosplenic ligament was dissected free, and the intra-abdominal esophagus was
      prepared. A posterior hiatoplasty was performed, followed by the 270 degrees 
      fundoplication. During the fundoplication, the esophagus was fixed to the crus
      and then the right and left wraps were fixed to the esophagus. Pneumoperitoneum
      was maintained stably throughout the LTF procedure, with optimal operative field.
      Total operating time for LTF was 90 min. Body temperature dropped from 37.4
      degrees C to 35.7 degrees C during pneumoperitoneum but resolved once
      pneumoperitoneum was ceased. Postoperative progress was uneventful, and an upper
      gastrointestinal study on postoperative day 2 showed no residual gastroesophageal
      reflux. DISCUSSION: We believe the AirSeal Intelligent Flow System and AP
      contributed to the successful completion of LTF in a 1.8-kg infant.

PMID- 26303739
TI  - Retroperitoneal schwannoma between the inferior vena cava and the abdominal aorta
      resected by laparoscopic surgery: A case report.
AB  - A 22-year-old woman presented with backache. Imaging analysis revealed a
      retroperitoneal tumor, 40 mm in diameter, surrounded by the abdominal aorta,
      inferior vena cava, caudate lobe of liver, and the left renal vein. The tumor
      consisted of multilocular cystic parts, and a solid part showed contrast
      enhancement. The possibility of malignancy could not be excluded, so we planned a
      laparoscopic tumorectomy. After placement of a transjugular vascular sheath for
      an occlusion balloon catheter in the inferior vena cava, the operation was
      performed with six ports. There was a strong fibrotic adhesion between the tumor
      and the abdominal aorta, with other weak adhesions. The tumor was successfully
      resected by a laparoscopic operation with minimal bleeding. The histopathological
      diagnosis was a benign schwannoma. This case demonstrates that a retroperitoneal
      tumor adjacent to major vessels can be resected safely by laparoscopic surgery if
      the surgeon is especially careful of the possibility of accidental bleeding. 

PMID- 26303740
TI  - [Segmental testicular infarction. Unusual complication of intravenous
      immunoglobulin therapy for multifocal motor neuropathy].
AB  - We describe the previously unknown case of segmental testicular infarction as an
      iatrogenic complication of intravenous immunoglobulin administration in a patient
      with multifocal motor neuropathy. 

PMID- 26303742
TI  - The effect of surface charge on the boundary slip of various oleophilic/phobic
      surfaces immersed in liquids.
AB  - The reduction of fluid drag is an important issue in many fluid flow applications
      at the micro/nanoscale. Boundary slip is believed to affect fluid drag. Slip
      length has been measured on various surfaces with different degrees of
      hydrophobicity and oleophobicity immersed in various liquids of scientific
      interest. Surface charge has been found to affect slip length in water and
      electrolytes. However, there are no studies on the effect of surface charge on
      slip at solid-oil interfaces. This study focuses on the effect of surface charge
      on the boundary slip of superoleophilic, oleophilic, oleophobic, and
      superoleophobic surfaces immersed in deionized (DI) water and hexadecane and
      ethylene glycol, based on atomic force microscopy (AFM). The surface charge was
      changed by applying a positive electric field to the solid-liquid interface, and
      by using liquids with different pH values. The results show that slip length
      increases with an increase in applied positive electric field voltage. Slip
      length also increases with a decrease in the pH of the solutions. The change in
      slip length is dependent on the absolute value of the surface charge, and a
      larger surface charge density results in a smaller slip length. In addition, the
      surface charge density at different solid-liquid interfaces is related to the
      dielectric properties of the surface. The underlying mechanisms are analyzed. 

PMID- 26303741
TI  - Effects of electroacupuncture therapy for Bell's palsy from acute stage: study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: Although many patients with facial paralysis have obtained benefits
      or completely recovered after acupuncture or electroacupuncture therapy, it is
      still difficult to list intuitive evidence besides evaluation using neurological
      function scales and a few electrophysiologic data. Hence, the aim of this study
      is to use more intuitive and reliable detection techniques such as facial nerve
      magnetic resonance imaging (MRI), nerve electromyography, and F waves to observe
      changes in the anatomic morphology of facial nerves and nerve conduction before
      and after applying acupuncture or electroacupuncture, and to verify their
      effectiveness by combining neurological function scales. METHODS/DESIGN: A total
      of 132 patients with Bell's palsy (grades III and IV in the House-Brackmann [HB]
      Facial Nerve Grading System) will be randomly divided into electroacupuncture,
      manual acupuncture, non-acupuncture, and medicine control groups. All the
      patients will be given electroacupuncture treatment after the acute period,
      except for patients in the medicine control group. The acupuncture or
      electroacupuncture treatments will be performed every 2 days until the patients
      recover or withdraw from the study. The primary outcome is analysis based on
      facial nerve functional scales (HB scale and Sunnybrook facial grading system),
      and the secondary outcome is analysis based on MRI, nerve electromyography and F
      wave detection. All the patients will undergo MRI within 3 days after Bell's
      palsy onset for observation of the signal intensity and facial nerve swelling of
      the unaffected and affected sides. They will also undergo facial nerve
      electromyography and F-wave detection within 1 week after onset of Bell's palsy.
      Nerve function will be evaluated using the HB scale and Sunnybrook facial grading
      system at each hospital visit for treatment until the end of the study. The MRI,
      nerve electromyography, and F-wave detection will be performed again at 1 month
      after the onset of Bell's palsy. TRIAL REGISTRATION: Chinese Clinical Trials
      Register identifier: ChiCTR-IPR-14005730. Registered on 23 December 2014.

PMID- 26303745
TI  - Optimal dosing of high-dose melphalan prior to autologous hematopoietic stem cell
      transplantation in a patient with AL amyloidosis and a solitary kidney.

PMID- 26303743
TI  - Human amniotic epithelial cells inhibit granulosa cell apoptosis induced by
      chemotherapy and restore the fertility.
AB  - INTRODUCTION: Premature ovarian failure and insufficiency are significant long
      term side-effects of chemotherapy for female cancer patients. Recently, stem cell
      transplantation has been identified as a promising treatment for premature
      ovarian failure and insufficiency. We have previously demonstrated that human
      amniotic epithelial cells (hAECs) migrate into injured tissue and promote the
      recovery of ovarian function in chemoablated mice. However, the molecular
      mechanism guiding this process remains unclear. METHODS: To further investigate
      the effect of hAECs on chemotherapy-induced apoptosis, cultured primary hAECs
      were injected intravenously into mice treated with cyclophosphamide and
      busulphan. Apoptosis of granulosa cells was observed by TUNEL staining, and
      apoptosis-related gene expression was performed on ovarian tissue by real-time
      PCR and Western blot 7 days after hAEC transplantation. Additionally, the ovarian
      function and fertility of mice were assessed via counts of follicles and mating
      experiments at 4 weeks after hAEC transplantation. RESULTS: hAECs significantly
      inhibited tumor necrosis factor-alpha-mediated granulosa cell apoptosis induced
      by chemotherapeutics and reduced the inflammatory reaction in ovaries at 7 days
      after transplantation. In addition, 4 weeks after transplantation, hAECs promoted
      the development of follicles and increased the number of cumulus oocyte complexes
      in chemoablated mice. Furthermore, hAECs improved ovarian mass and increased the
      number of follicles compared to those of the chemoablated group, and hAEC
      transplantation partially rescued the fertility of chemoablated mice.
      CONCLUSIONS: hAEC transplantation promotes ovarian function by inhibiting tumor
      necrosis factor-alpha-mediated cell apoptosis and reducing inflammation in
      chemotherapy-induced premature ovarian failure. These results suggest a potential
      molecular mechanism for the effective therapy of hAEC transplantation in
      chemotherapy-induced premature ovarian failure and insufficiency.

PMID- 26303746
TI  - Development of CYP11B1 and CYP11B2 assays utilizing homogenates of adrenal
      glands: Utility of monkey as a surrogate for human.
AB  - Elevated levels of aldosterone are associated with arterial hypertension,
      congestive heart failure, chronic kidney disease, and obesity. Aldosterone is
      produced predominantly in the zona glomerulosa of the cortex of the adrenal gland
      by the enzyme aldosterone synthase (CYP11B2). Treatment of the above indications
      by decreasing production of aldosterone is thought to be of therapeutic benefit
      by lessening the deleterious effects of aldosterone mediated through both the
      mineralocorticoid receptor and also through so called non-genomic pathways.
      However, inhibition of the highly similar enzyme, CYP11B1, which is responsible
      for the production of cortisol, must be avoided in the development of clinically
      useful aldosterone synthase inhibitors due to the resulting impairment of the
      cortisol-induced stress response. In efforts to assess the interactions of
      compounds with the CYP11B enzymes, a variety of cell-based inhibitor screening
      assays for both CYP11B1 and CYP11B2 have been reported. Herein we report details
      of assays employing both cynomolgus monkey adrenal homogenate (CAH) and human
      adrenal homogenate (HAH) as sources of CYP11B1 and CYP11B2 enzymes. Utilizing
      both CAH and HAH, we have characterized the kinetics of the CYP11B1-mediated
      conversion of 11-deoxycortisol to cortisol and the CYP11B2-mediated oxidation of
      corticosterone to aldosterone. Inhibition assays for both CYP11B1 and CYP11B2
      were subsequently developed. Based on a comparison of human and monkey amino acid
      sequences, kinetics data, and inhibition values derived from the HAH and CAH
      assays, evidence is provided in support of using cynomolgus monkey tissue-derived
      cell homogenates as suitable surrogates for the human enzymes. 

PMID- 26303747
TI  - A novel, fully-automated, chemiluminescent assay for the detection of 1,25
      dihydroxyvitamin D in biological samples.
AB  - BACKGROUND: 1,25-Dihydroxyvitamin D (1,25-(OH)2D), the hormonal form of vitamin
      D, is difficult to measure because of its low circulating levels (pg/mL), and
      similarity to more abundant metabolites. Here a fully-automated chemiluminescent
      assay that accurately and precisely measures 1,25-(OH)2D is described. METHOD:
      The novel 1,25-(OH)2D assay was conceived based on four pillars: (1) the VDR's
      ligand binding domain (LBD) as a capture molecule; (2) reaction conditions
      wherein 1,25-(OH)2D favors binding to LBD vs. the vitamin D binding protein; (3)
      exploitation of liganded-LBD's conformational change; (4) a monoclonal antibody
      specific to liganded-LBD. This specific, conformational, sandwich approach,
      unique for automated measurement of haptens, is superior to more cumbersome,
      conventional competitive formats. RESULTS: Accuracy of the 1,25-(OH)2D assay was
      corroborated by its alignment against LC-MS/MS with fit Deming regression
      equations of y=0.98x + 1.93 (r=0.92), and y=1.07x+3.77 (r=0.94) for different
      methods from Endocrine Sciences, Laboratory Corporation of America(r) and the
      University of Washington, respectively. Good analytical precision was manifested
      by its low estimated limit of quantitation (1.57pg/mL), average intra-assay
      imprecision (3.5%CV; range 1.1-4.7%), and average inter-assay imprecision
      (4.5%CV; range 3.4-7.2%). Expected and measured recovery values were congruent
      (93.4% mean). CONCLUSIONS: The novel 1,25-(OH)2D method exhibited excellent
      correlation with well validated LC-MS/MS assays from two laboratories.
      Significantly, its 65min turn-around time is quicker, and sample volume smaller
      (75MUl) than current methods.

PMID- 26303748
TI  - Role of endothelial cells in bovine mammary gland health and disease.
AB  - The bovine mammary gland is a dynamic and complex organ composed of various cell
      types that work together for the purpose of milk synthesis and secretion. A layer
      of endothelial cells establishes the blood-milk barrier, which exists to
      facilitate the exchange of solutes and macromolecules necessary for optimal milk
      production. During bacterial challenge, however, endothelial cells divert some of
      their lactation function to protect the underlying tissue from damage by
      initiating inflammation. At the onset of inflammation, endothelial cells tightly
      regulate the movement of plasma components and leukocytes into affected tissue.
      Unfortunately, endothelial dysfunction as a result of exacerbated or sustained
      inflammation can negatively affect both barrier integrity and the health of
      surrounding extravascular tissue. The objective of this review is to highlight
      the role of endothelial cells in supporting milk production and regulating
      optimal inflammatory responses. The consequences of endothelial dysfunction and
      sustained inflammation on milk synthesis and secretion are discussed. Given the
      important role of endothelial cells in orchestrating the inflammatory response, a
      better understanding of endothelial function during mastitis may support
      development of targeted therapies to protect bovine mammary tissue and mammary
      endothelium. 

PMID- 26303749
TI  - Emergence of nutrient co-limitation through movement in stoichiometric meta
      ecosystems.
AB  - Evidence that ecosystems and primary producers are limited in their productivity
      by multiple nutrients has caused the traditional nutrient limitation framework to
      include multiple limiting nutrients. The models built to mimic these responses
      have invoked local mechanisms at the level of the primary producers. In this
      paper, we explore an alternative explanation for the emergence of co-limitation
      by developing a simple, stoichiometrically explicit meta-ecosystem model with two
      limiting nutrients, autotrophs and herbivores. Our results show that differences
      in movement rates for the nutrients, autotrophs and herbivores can allow for
      nutrient co-limitation in biomass response to emerge despite no local mechanisms
      of nutrient co-limitation. Furthermore, our results provide an explanation to why
      autotrophs show positive growth responses to nutrients despite 'nominal' top-down
      control by herbivores. These results suggest that spatial processes can be
      mechanisms for nutrient co-limitation at local and regional scales, and can help
      explain anomalous results in the co-limitation literature.

PMID- 26303750
TI  - Differences in maternal temperature during labour with remifentanil patient
      controlled analgesia or epidural analgesia: a randomised controlled trial.
AB  - BACKGROUND: Epidural analgesia and remifentanil patient-controlled analgesia are
      two popular techniques for the treatment of labour pain, each with its own
      efficacy and toxicity. METHODS: Parturients requesting analgesia were randomly
      assigned to either patient-controlled intravenous remifentanil or epidural
      analgesia. Control patients consisted of parturients not requesting pain
      medication. The primary objective was to compare the incidence of maternal fever
      (temperature ? 38 degrees C); secondary outcomes included the incidence of low
      oxygen saturation, pain scores, nausea and vomiting, sedation scores, pruritus
      and neonatal outcome. RESULTS: Data from 140 parturients were analysed: 49
      received remifentanil analgesia, 49 epidural analgesia and 42 no analgesia
      (controls). Fever (temperature ? 38 degrees C) developed in 10% of remifentanil
      patients compared to 37% of epidural patients and 7% of control patients
      (P<0.001). One or more hypoxaemic events (oxygen saturation <90% for at least 1
      min) occurred in 48% of patients on remifentanil versus 15% of patients on
      epidural analgesia and 20% of control patients (P=0.003). Although pain intensity
      scores differed significantly between the two groups in favour of the epidural,
      mean satisfaction scores were similar in both analgesia groups (remifentanil 8.1
      +/- 1.2 vs. epidural 8.4 +/- 1.2). Remifentanil analgesia was associated with a
      higher incidence of nausea and deeper levels of sedation. The differences in
      haemodynamic parameters between groups were small and clinically insignificant.
      CONCLUSIONS: During treatment of labour pain, epidural analgesia is associated
      with a higher incidence of maternal fever, while remifentanil analgesia results
      in more frequent and deeper hypoxaemic events.

PMID- 26303751
TI  - Failed tracheal intubation during obstetric general anaesthesia: a literature
      review.
AB  - We reviewed the literature on obstetric failed tracheal intubation from 1970
      onwards. The incidence remained unchanged over the period at 2.6 (95% CI 2.0 to
      3.2) per 1000 anaesthetics (1 in 390) for obstetric general anaesthesia and 2.3
      (95% CI 1.7 to 2.9) per 1000 general anaesthetics (1 in 443) for caesarean
      section. Maternal mortality from failed intubation was 2.3 (95% CI 0.3 to 8.2)
      per 100000 general anaesthetics for caesarean section (one death per 90 failed
      intubations). Maternal deaths occurred from aspiration or hypoxaemia secondary to
      airway obstruction or oesophageal intubation. There were 3.4 (95% CI 0.7 to 9.9)
      front-of-neck airway access procedures (surgical airway) per 100000 general
      anaesthetics for caesarean section (one procedure per 60 failed intubations),
      usually carried out as a late rescue attempt with poor maternal outcomes. Before
      the late 1990s, most cases were awakened after failed intubation; since the late
      1990s, general anaesthesia has been continued in the majority of cases. When
      general anaesthesia was continued, a laryngeal mask was usually used but with a
      trend towards use of a second-generation supraglottic airway device. A
      prospective study of obstetric general anaesthesia found that transient maternal
      hypoxaemia occurred in over two-thirds of cases of failed intubation, usually
      without sequelae. Pulmonary aspiration occurred in 8% but the rate of maternal
      intensive care unit admission after failed intubation was the same as that after
      uneventful general anaesthesia. Poor neonatal outcomes were often associated with
      preoperative fetal compromise, although failed intubation and lowest maternal
      oxygen saturation were independent predictors of neonatal intensive care unit
      admission. 

PMID- 26303752
TI  - Anaesthetic management of a parturient with factor VII deficiency and sepsis.

PMID- 26303753
TI  - Utilization of spinal anesthesia for external cephalic version: a clinical
      practice cohort analysis.

PMID- 26303754
TI  - Large intracranial subdural haematoma with midline shift following accidental
      dural puncture for labour analgesia.

PMID- 26303755
TI  - Subdural hematoma with cranial nerve palsies after obstetric epidural analgesia.

PMID- 26303756
TI  - Maternal collapse secondary to aortocaval compression.

PMID- 26303757
TI  - Type 1, type 2 and gestational diabetes mellitus differentially impact placental
      pathologic characteristics of uteroplacental malperfusion.
AB  - INTRODUCTION: During a pregnancy complicated by diabetes, the placenta undergoes
      a number of functional and structural pathologic changes. However, differences
      across studies may reflect pathophysiologic differences of diabetes types under
      investigation. METHODS: We examined placental pathology from women ages 18-40
      years with self-identified race/ethnicity; singleton, live births; and type 1
      (T1DM; n = 36), type 2 (T2DM; n = 37), or gestational diabetes mellitus (GDM; n =
      126). Clinical data were abstracted from medical records. Placental diagnoses
      were independently re-reviewed by a perinatal pathologist. Multivariable analyses
      adjusting for race, gestational weight gain, gestational age, and systolic blood
      pressure were conducted. RESULTS: Women with T1DM compared with either T2DM or
      GDM had higher gestational weight gain (mean +/- SD, T1DM vs. T2DM: 28.5 +/- 12.4
      vs. 20.5 +/- 13.4 kg, p = 0.03; or GDM: 21.3 +/- 12.7 kg, p = 0.009) and insulin
      use (T2DM: 100.0% vs. 85.3%, p = 0.02; or GDM: 4.0%, p < 0.001). Women with T1DM
      compared with either T2DM or GDM also had a similarly lower prevalence of
      placental infarcts in univariate analyses; however, these findings did not remain
      significant after multivariable adjustment. Also, placentas from women with T2DM
      compared to GDM had higher rates of decidual vasculopathy when excluding women
      with preeclampsia (10.3 vs. 1.6%, p = 0.049) and diffuse chorangiosis (62.2 vs.
      32.5%, p < 0.001) but a lower rate of villous immaturity (10.8 vs. 90.5%, p =
      0.007) after full adjustment. DISCUSSION: Placental vasculopathic abnormalities
      differ by maternal diabetes type, potentially reflecting underlying
      pathophysiologic mechanisms. Further research on placental pathology and
      metabolic derangements is warranted.

PMID- 26303758
TI  - Sildenafil (Viagra(r)) blocks inflammatory injury in LPS-induced mouse abortion:
      A potential prophylactic treatment against acute pregnancy loss?
AB  - INTRODUCTION: Recurrent pregnancy losses (RPL) are common women's health issues.
      Inflammatory and thrombotic events have been associated with RPL including
      excessive production of cytokines, in particular TNF-alpha. However, mechanisms
      behind gestational losses are not yet fully understood. Sildenafil inhibits
      phosphodiesterase Type-5 (PDE5). This drug increases intracellular cyclic
      guanosine monophosphate, having vasodilatory and, more recently described, anti
      inflammatory properties. PDE5 is present in murine and human uterus and placenta.
      Sildenafil is already used clinically for treatment of human fetal growth
      restriction (FGR). Our objective was to determine if Sildenafil alone or in
      combination with Heparin had protective effects in pregnant Swiss albino
      challenged to abort by lipopolysaccharide (LPS). METHODS: Treatments (Sildenafil
      (50 mg/kg/day), Heparin (500 IU/Kg/day) or Sildenafil + Heparin at the same
      doses) were initiated the morning of copulation plug detection (gestational day
      (gd0)). On the 15th day of pregnancy, an intra-peritoneal injection of LPS (100
      MUg/kg) was administered. Untreated, pregnant mice challenged by LPS served as
      controls. RESULTS: Assessments at 48 h after LPS revealed that Sildenafil +
      Heparin prevented fetal loss. Early assessments at 2 h after LPS indicated that
      the pretreatments prevented induction of inflammatory cytokine production (TNF
      alpha, IL-1beta/NF-kappabeta) and preserved placental histopathology. DISCUSSION:
      Combined Sildenafil + Heparin therapy was superior to either treatment alone in
      most analyses. The known safety of Sildenafil and Heparin in human pregnancy
      suggests that usage of these combined agents may be of value for treatment of
      patients with impending pregnancy loss or prophylactically in women with a
      history of recurrent miscarriages.

PMID- 26303759
TI  - HMGB1-RAGE signaling pathway in severe preeclampsia.
AB  - INTRODUCTION: Placental dysfunction and increased inflammation are believed to
      underlie the pathogenesis of severe preeclampsia (PE). High-mobility group box 1
      (HMGB1), a recently identified inflammatory cytokine, has been known to
      contribute to the development of inflammatory responses in PE. This study intends
      to elucidate the mechanisms of HMGB1-RAGE signaling pathway in the pathogenesis
      of PE. METHODS: The mRNA levels of relative gene of HMGB1 pathway, HMGB1, RAGE
      and NF-kappaB p65, were analyzed by real-time PCR in placentas collected from 61
      normotensive pregnant women and 64 women with severe PE. Additionally, levels of
      HMGB1 and RAGE protein were detected in frozen placental specimens by western
      blot, and the locations of them were evaluated in the well-characterized tissue
      microarray by immunohistochemistry. ELISA was further used to detect HMGB1 level
      in maternal serum. RESULTS: Compared with matched control placentas, the mRNA
      levels of HMGB1, RAGE and NF-kappaB p65 were increased in severe preeclamptic
      placentas. In severe preeclamptic placentas, HMGB1 and RAGE immunoreactivity were
      increased in the cytoplasm of trophoblast cells. Western blot was employed to
      further confirm that RAGE protein level was elevated significantly in severe PE
      group. In addition, there was an increased level of HMGB1 in the maternal serum
      of severe PE group. DISCUSSION: HMGB1 nuclear-cytoplasmic translocation may
      induce the binding of HMGB1 to its receptors, consequently, intrigue NF-kappaB
      activity in severe PE. HMGB1-RAGE signaling pathway may be involved in the
      pathogenesis of PE.

PMID- 26303760
TI  - Organic anion transporter 4 (OAT 4) modifies placental transfer of perfluorinated
      alkyl acids PFOS and PFOA in human placental ex vivo perfusion system.
AB  - INTRODUCTION: Perfluorinated alkyl acids (PFAAs) are widely used in industry and
      consumer products. Pregnant women are exposed to PFAAs and their presence in
      umbilical cord blood represents fetal exposure. Interestingly, PFAAs are
      substrates for organic anion transporters (OAT) of which OAT4 is expressed in
      human placenta. METHODS: To evaluate the contribution of OAT4 and ATP-binding
      cassette transporter G2 (ABCG2) proteins in the transplacental transfer of
      perfluoro octane sulfonate (PFOS) and perfluoro octanoate (PFOA) an ex vivo dual
      recirculating human placental perfusion was used. Altogether 8 placentas from
      healthy mothers with uncomplicated pregnancies were successfully perfused.
      RESULTS: Both PFOS and PFOA crossed the placenta as suggested by in vivo data in
      the literature. The expression of OAT4 and ABCG2 proteins were studied by
      immunoblotting and correlation with the transfer index %(TI %) of PFOS and PFOA
      at 120 and 240 min (n = 4) was studied. The expression of OAT4 was in negative
      correlation with TI % of PFOA (R(2) = 0.92, p = 0.043) and PFOS (R(2) = 0.99, p =
      0.007) at 120 min while at 240 min the correlation was statistically significant
      only with PFOA. The expression of ABCG2 did not correlate with TI% of PFOS or
      PFOA. DISCUSSION: Data obtained in this study suggest the involvement of OAT4 in
      placental passage of PFAAs. Placental passage of PFOS and PFOA is modified by the
      transporter protein OAT4 but not by ABCG2. This is the first study indicating
      that OAT4 may decrease the fetal exposure to PFAAs and protect the fetus after
      maternal exposure to PFAAs but further studies are needed to confirm our
      findings.

PMID- 26303761
TI  - Japanese population norms for preference-based measures: EQ-5D-3L, EQ-5D-5L, and
      SF-6D.
AB  - PURPOSE: The purpose of this study was to measure the population norms for the
      Japanese versions of preference-based measures (EQ-5D-3L, EQ-5D-5L, and SF-6D).
      We also considered the relations between QOL score in the general population and
      socio-demographic factors. METHODS: A total of 1143 adult respondents (aged >= 20
      years) were randomly sampled from across Japan using data from the Basic Resident
      Register. The health status of each respondent was measured using the EQ-5D-3L,
      EQ-5D-5L, and SF-6D, and responses regarding socio-demographic data as well as
      subjective diseases and symptoms were obtained. The responses were converted to a
      QOL score using Japanese value sets. RESULTS: The percentages of respondents with
      full health scores were 68 % (EQ-5D-3L), 55 % (EQ-5D-5L), and 4 % (SF-6D). The
      QOL score measured using the SF-6D was significantly lower than those measured
      using either EQ-5D score. The QOL score was significantly lower among respondents
      over the age of 60 years, those who had a lower income, and those who had a
      shorter period of education. Intraclass correlation coefficient showed a poor
      agreement between the EQ-5D and SF-6D scores. The differences in QOL scores
      between respondents with and those without any disease were 0.064 for the EQ-5D
      3L, 0.061 for the EQ-5D-5L, and 0.073 for the SF-6D; these differences are
      regarded as between-group minimal important differences in the general
      population. CONCLUSION: The Japanese population norms of three preference-based
      QOL measures were examined for the first time. Such information is useful for
      economic evaluations and research examining QOL score.

PMID- 26303762
TI  - Age estimation based on aspartic acid racemization in human sclera.
AB  - Age estimation based on racemization of aspartic acid residues (AAR) in permanent
      proteins has been established in forensic medicine for years. While dentine is
      the tissue of choice for this molecular method of age estimation, teeth are not
      always available which leads to the need to identify other suitable tissues. We
      examined the suitability of total tissue samples of human sclera for the
      estimation of age at death. Sixty-five samples of scleral tissue were analyzed.
      The samples were hydrolyzed and after derivatization, the extent of aspartic acid
      racemization was determined by gas chromatography. The degree of AAR increased
      with age. In samples from younger individuals, the correlation of age and D
      aspartic acid content was closer than in samples from older individuals. The age
      dependent racemization in total tissue samples proves that permanent or at least
      long-living proteins are present in scleral tissue. The correlation of AAR in
      human sclera and age at death is close enough to serve as basis for age
      estimation. However, the precision of age estimation by this method is lower than
      that of age estimation based on the analysis of dentine which is due to molecular
      inhomogeneities of total tissue samples of sclera. Nevertheless, the approach may
      serve as a valuable alternative or addition in exceptional cases. 

PMID- 26303764
TI  - Response to Letter to the Editor: Effects of New Antiplatelet Agents and
      Aldosterone Receptor Antagonists on Mortality in Patients with Myocardial
      Infarction.

PMID- 26303763
TI  - Wet-chemical synthesis and applications of non-layer structured two-dimensional
      nanomaterials.
AB  - Non-layer structured nanomaterials with single- or few-layer thickness have two
      dimensional sheet-like structures and possess intriguing properties. Recent years
      have seen major advances in development of a host of non-layer structured
      ultrathin two-dimensional nanomaterials such as noble metals, metal oxides and
      metal chalcogenides. The wet-chemical synthesis has emerged as the most promising
      route towards high-yield and mass production of such nanomaterials. These
      nanomaterials are now finding increasing applications in a wide range of areas
      including catalysis, energy production and storage, sensor and nanotherapy, to
      name but a few. 

PMID- 26303765
TI  - Statin-Induced Cardioprotection Against Ischemia-Reperfusion Injury: Potential
      Drug-Drug Interactions. Lesson to be Learnt by Translating Results from Animal
      Models to the Clinical Settings.
AB  - Numerous interventions have been shown to limit myocardial infarct size in animal
      models; however, most of these interventions have failed to have a significant
      effect in clinical trials. One potential explanation for the lack of efficacy in
      the clinical setting is that in bench models, a single intervention is studied
      without the background of other interventions or modalities. This is in contrast
      to the clinical setting in which new medications are added to the "standard of
      care" treatment that by now includes a growing number of medications. Drug-drug
      interaction may lead to alteration, dampening, augmenting or masking the effects
      of the intended intervention. We use the well described model of statin-induced
      myocardial protection to demonstrate potential interactions with agents which are
      commonly concomitantly used in patients with stable coronary artery disease
      and/or acute coronary syndromes. These interactions could potentially explain the
      reduced efficacy of statins in the clinical trials compared to the animal models.
      In particular, caffeine and aspirin could attenuate the infarct size limiting
      effects of statins; morphine could delay the onset of protection or mask the
      protective effect in patients with ST elevation myocardial infarction, whereas
      other anti-platelet agents (dipyridamole, cilostazol and ticagrelor) may augment
      (or mask) the effect due to their favorable effects on adenosine cell reuptake
      and intracellular cAMP levels. We recommend that after characterizing the effects
      of new modalities in single intervention bench research, studies should be
      repeated in the background of standard-of-care medications to assure that the
      magnitude of the effect is not altered before proceeding with clinical trials. 

PMID- 26303766
TI  - Laparoscopic Extravesical Lich-Gregoir Ureteroneocystostomy with Psoas Hitch for
      the Management of Ureterovaginal Fistula in Post-Hysterectomy Patients.
AB  - INTRODUCTION: Most commonly ureterovaginal fistula occurs due to surgical injury
      inflicted to the distal ureter and because of gynaecological procedures. Open
      surgical repair is a standard procedure and commonly involves
      ureteroneocystostomy. METHODS: We retrospectively reviewed data of 9 patients,
      who underwent laparoscopic extravesical Lich-Gregoir ureteroneocystostomy using
      the psoas hitch procedure for ureterovaginal fistulas following hysterectomy
      during the period December 2012-August 2014. Transperitoneal laparoscopic
      ureteroneocystostomy was performed in all cases. RESULTS: The mean operative time
      was 212 min (range 170-310) and estimated blood loss was 108 ml (range 70-150).
      Average hospital stay was 5.7 days. Follow-up time was from 6 to 26 months.
      Postoperative intravenous urography was done after 3 months, which showed patent
      anastomosis in 8 patients except for 1 patient who had nonvisualization of the
      ipsilateral renal moiety. Voiding cystogram done at 3 months showed no leakage in
      all patients. In the postoperative period, 1 patient had recurrent ipsilateral
      pyelonephritis 2 weeks after surgery, while another patient had febrile UTI.
      Apart from these no major complications were observed. CONCLUSION: Laparoscopic
      ureteroneocystostomy with psoas hitch can be performed safely with a success rate
      compared to that of open surgery but with less morbidity and quick convalescence.

PMID- 26303767
TI  - Sphaerisporangium aureirubrum sp. nov., an actinomycete isolated from soil.
AB  - A novel actinomycete, designated strain NEAU-GQTH1-3T, was isolated from muddy
      soil collected from a stream in Qitaihe, Heilongjiang Province, north-east China
      and characterized using a polyphasic approach. Phylogenetic analysis based on the
      16S rRNA gene sequence indicated that the organism should be assigned to the
      genus Sphaerisporangium and forms a stable clade with its closest relative
      Sphaerisporangium rubeum JCM 13067T (98.2 % 16S rRNA gene sequence similarity).
      Moreover, morphological and chemotaxonomic properties of strain NEAU-GQTH1-3T
      also confirmed the affiliation of the isolate to the genus Sphaerisporangium. The
      cell wall contained meso-diaminopimelic acid and the whole-cell sugars were
      glucose, galactose, madurose, mannose and ribose. The polar lipid profile
      consisted of diphosphatidylglycerol, phosphatidylethanolamine,
      phosphatidylmethylethanolamine, phosphatidylinositol, two phosphatidylinositol
      mannosides, phosphoglycolipid, an unidentified phospholipid and an unidentified
      glycolipid. The major menaquinones were MK-9(H4), MK-9(H6) and MK-9(H2). The
      predominant cellular fatty acids were iso-C16 : 0 and 10-methyl C17 : 0. Mycolic
      acids were absent. The DNA G+C content was 70.4 mol%. However, the low level of
      DNA-DNA relatedness and some phenotypic characteristics allowed the isolate to be
      differentiated from its closest relative. Therefore, it is concluded that strain
      NEAU-GQTH1-3T represents a novel species of the genus Sphaerisporangium, for
      which the name Sphaerisporangium aureirubrum sp. nov. is proposed. The type
      strain is NEAU-GQTH1-3T ( = CGMCC 4.7199T = JCM 30346T).

PMID- 26303768
TI  - Induction of protective and therapeutic anti-cancer immunity by using bispecific
      anti-idiotype antibody G22-I50 for nasopharyngeal carcinoma.
AB  - Increasing evidence has suggested that bispecific and multivalent antibodies
      which have more antigen binding sites will improve their immunogenicity. The
      bispecific anti-idiotype antibody vaccine G22-I50 was obtained through genetic
      engineering to enhance the immunogenicity of anti-idiotype antibody vaccines G22
      and I50. G22-I50 vaccination could induce anti-tumor immunity in the Balb/c mouse
      model. The protective and therapeutic efficacy of G22-I50 was also evaluated
      using the hu-PBL-SCID mouse model injected three times with G22-I50, G22, or I50
      mixed with Freund's adjuvant. Results demonstrated that the protective anti-tumor
      effect of G22-I50 could be relevant with the production of Ab3 antibody and
      activation of CD8(+) cytotoxic T-lymphocytes. In preventive and therapeutic
      experiments, G22-I50 could reduce tumor size and prolong the survival time of
      HNE2-bearing mice (p<0.05). Human CD8(+) T lymphocytes infiltrated the tumor
      sites, and high levels of human IFN-gamma, TNF-alpha, and caspase-3 were also
      detected in the tumors from G22-I50-vaccinated and -treated mice. Therefore, the
      bispecific anti-idiotype antibody vaccine G22-I50 can induce strong humoral and
      cell-mediated immune responses. This vaccine can be potentially applied to
      prevent and treat nasopharyngeal carcinoma. 

PMID- 26303769
TI  - TNF-alpha modulates the immunosuppressive effects of MSCs on dendritic cells and
      T cells.
AB  - Mesenchymal stem cells are progenitor cells that have capabilities to
      differentiate different cell types. Also, MSCs possess immune suppressive effects
      on DC differentiation and T cell activation through a wide range of soluble
      factors and receptors. The properties of MSCs change through activation of
      cytokines particularly IFN-gamma and TNF-alpha. The DC phenotypes and functions
      including the expression of co-stimulatory and co-inhibitory molecules and
      capabilities of DCs to induce allogeneic activation of CFSE-labeled splenocytes
      as well as cytokine production when they were differentiated in the presence of
      MSCs, TNF-alpha activated MSCs, IFN-gamma activated MSCs and IFN-gamma & TNF
      alpha activated MSCs were analyzed. Treg population and T cell polarization were
      investigated using flowcytometry and real-time PCR respectively. Here, we showed
      that IFN-gamma slightly enhances immunosuppressive effects of MSCs on immune
      system through induction tolerogenic DCs with elevated expression of IDO and
      increasing Treg population. Conversely, TNF-alpha decreases immunomodulation
      properties of MSCs on immune cells through the enhancement of co-stimulatory
      molecules such as ICOSL and HLA-DR, reduction of PDL-1 and PDL-2 expression and
      decrease of TGF-beta and IL-10 in DCs as well as inhibition of T cell
      polarization into TH2 and Treg. Taken together, these data showed crucial effects
      of microenvironments on MSC behaviors indicating that functions of MSCs
      differentially altered in the presence of different cytokines. 

PMID- 26303770
TI  - AA092, an annonaceous acetogenin mimetic, attenuates angiogenesis in a mouse
      model of inflammation-induced corneal neovascularization.
AB  - Previous studies demonstrated that annonaceous acetogenin (AA) was an antitumor
      drug with anti-angiogenic activity. However, the effect of AA on ocular
      neovascular disorders remains unclear. The aim of the present study is to explore
      the effect of AA092, an annonaceous acetogenin mimetic, on corneal
      neovascularization (CNV). In a mouse model of alkali-induced CNV, topical
      application of AA092 to the injured corneas attenuated CNV. In addition, in vivo
      treatment with AA092 down-regulated the expression of the pro-angiogenic factors
      VEGF, b-FGF, TGFbeta1, EGF but up-regulated the expression of the anti-angiogenic
      factors Thrombospondin-1 (Tsp-1), Tsp-2 and ADAMTS-1 in the injured corneas.
      Furthermore, AA092 inhibited the expression of pro-angiogenic factors, migration,
      proliferation and tube formation by human microvascular endothelial cells (HEMC
      1) in vitro. These data indicate that AA092 has therapeutic potential for
      angiogenesis-associated diseases such as CNV. 

PMID- 26303771
TI  - Antimicrobial and cytotoxicity properties of the crude extracts and fractions of
      Premna resinosa (Hochst.) Schauer (Compositae): Kenyan traditional medicinal
      plant.
AB  - BACKGROUND: Premna resinosa (Hochst.) Schauer also called "mukarakara" in Mbeere
      community of Kenya is used in the management of respiratory illness. In this
      study we investigated antituberculous, antifungal, antibacterial activities
      including cytotoxicity and phytochemical constituents of this plant. METHODS:
      Antibacterial and antifungal activities were investigated by disc diffusion and
      micro dilution techniques. Antituberculous activity was investigated using BACTEC
      MGIT 960 system while cytotoxicity was analyzed by MTT assay on Vero cells
      (Methanolic crude extract) and HEp-2 cells (fractions). Finally, phytochemicals
      were profiled using standard procedures. RESULTS: P. resinosa had high
      antituberculous activity with a MIC of <6.25 MUg/ml in ethyl acetate fraction.
      The antibacterial activity was high and broad spectrum, inhibiting both Gram
      positive and Gram negative bacteria. Dichloromethane fraction had the best
      antibacterial MIC of 31.25 MUg/ml against Methicillin-resistant S. aureus while
      Ethyl acetate fraction had the highest zone of inhibition of 22.3+/-0.3 against
      S. aureus. Its effects on tested fungi were moderate with petro ether fraction
      giving an inhibition of 10.3+/-0.3 on C. albicans. The crude extract and two
      fractions (petro ether and methanol) were not within the acceptable toxicity
      limits, however dichloromethane and ethyl acetate fractions that exhibited higher
      activity were within the acceptable toxicity limit (CC50<90). The activity can to
      some extent be associated to alkaloids, flavonoids, terpenoids, anthraquinones
      and phenols detected in this plant extracts. CONCLUSION: Our findings demonstrate
      that P. resinosa has high selective potential as a source of novel lead for
      antituberculous, antibacterial and antifungal drugs. Of particular relevance is
      high activity against MRSA, S. aureus, C. albicans and MTB which are great public
      health challenge due to drug resistance development and as major sources of
      community and hospital based infections.

PMID- 26303772
TI  - Association between adverse pregnancy outcome and imbalance in angiogenic
      regulators and oxidative stress biomarkers in gestational hypertension and
      preeclampsia.
AB  - BACKGROUND: Gestational hypertension (GH) and Preeclampsia, (PE) are the most
      complicated amongst hypertensive disorders of pregnancy. The mechanism that links
      hypertension in pregnancy to adverse maternal outcomes is not fully understood
      though some relate this to endothelial dysfunction originating from an imbalanced
      angiogenic regulators and oxidative stress biomarkers. This study assessed the
      correlation between angiogenic regulators and oxidative stress biomarker levels
      with adverse pregnancy outcomes among GH and PE participants. METHODS: A cohort
      of pregnant women who received antenatal care at the Obstetrics and Gynaecology
      department of the Komfo Anokye Teaching Hospital (KATH) were followed. During
      their antenatal visits, 100 developed PE and 70 developed GE, of these, 50 PE and
      50 GH gave informed consent. Their blood samples were taken at time of diagnosis
      and 48 h post-partum. 50 other aged-matched women who did not develop neither GH
      nor PE were selected as controls. Placental growth factor (PLGF), soluble fms
      like tyrosine kinase 1 (sFlt-1) and 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha)
      levels were estimated by ELISA and total antioxidant capacity (T-AOC) was
      measured spectrophotometrically. Graphpad Prism was used for data analysis.
      RESULTS: Median levels of sFlt-1, 8-epi-PGF2alpha and sFlt-1/PLGF were elevated
      among participants with PE co-existing with intrauterine fetal death (IUFD),
      placental abruptio, placental previa, HELLP syndrome and intrauterine growth
      restriction (IUGR) compared to PE without adverse outcomes (p = 0.041, p = 0.005,
      p = 0.0002). Levels of PLGF, T-AOC and PLGF/sFlt-1 were significantly reduced
      among participants with PE co-existing with IUFD, placental abruptio, placental
      previa, HELLP syndrome and IUGR compared to PE without adverse outcomes (p =
      0.0013, p = 0.006, p < 0.0001). A significant negative correlation of IUGR (p =
      0.0030; p < 0.0001), placental abruptio (p < 0.0001; p < 0.0001), IUFD (p <
      0.0001; p < 0.0001), stillbirth (p = 0.0183 and p < 0.000), and postpartum
      haemorrhage (PPH) (p = 0.0420; p = 0.0044) were associated with both PLGF and T
      AOC whilst a significant positive correlation of IUGR, placental abruptio (p <
      0.0001; p < 0.0001), IUFD (p < 0.0001; p < 0.0001), stillbirth (p < 0.0001; p <
      0.0001), and PPH (p = 0.0043; p = 0.0039) were observed with both sFlt-1 and 8
      epi-PGF2alpha in PE. CONCLUSIONS: Imbalance in the levels of angiogenic
      regulators and oxidative stress biomarkers correlates with adverse pregnancy
      outcomes among PE participants. Early identification of these imbalance would
      alert health care givers in anticipation of adverse pregnancy outcome and thus
      increased surveillance during pregnancy and parturition and measures to
      ameliorate the adverse outcome.

PMID- 26303773
TI  - Misunderstandings about Q and 'Cochran's Q test' in meta-analysis.
AB  - Many meta-analyses report using 'Cochran's Q test' to assess heterogeneity of
      effect-size estimates from the individual studies. Some authors cite work by W.
      G. Cochran, without realizing that Cochran deliberately did not use Q itself to
      test for heterogeneity. Further, when heterogeneity is absent, the actual null
      distribution of Q is not the chi-squared distribution assumed for 'Cochran's Q
      test'. This paper reviews work by Cochran related to Q. It then discusses
      derivations of the asymptotic approximation for the null distribution of Q, as
      well as work that has derived finite-sample moments and corresponding
      approximations for the cases of specific measures of effect size. Those results
      complicate implementation and interpretation of the popular heterogeneity index
      I(2) . Also, it turns out that the test-based confidence intervals used with I(2)
      are based on a fallacious approach. Software that outputs Q and I(2) should use
      the appropriate reference value of Q for the particular measure of effect size
      and the current meta-analysis. Q is a key element of the popular DerSimonian
      Laird procedure for random-effects meta-analysis, but the assumptions of that
      procedure and related procedures do not reflect the actual behavior of Q and may
      introduce bias. The DerSimonian-Laird procedure should be regarded as unreliable.

PMID- 26303774
TI  - Self-organisation of inorganic elements on Si(001) mediated by pre-adsorbed
      organic molecules.
AB  - A combined theoretical and experimental study on the adsorption of an isolated
      benzonitrile molecule on the Si(001) surface, followed by the adsorption of Al
      (group III), Pb (carbon group) and Ag (transition metal) is presented. It is
      shown that two new adsorption sites with enhanced reactivity are formed on the
      surface in the vicinity of the pre-adsorbed molecule. This is evidenced by the
      increase of the calculated binding energy of the metallic ad-atoms adsorbed at
      these sites. Experimentally, this enhanced local reactivity of the modified
      surface is only partially retained when more metallic atoms are adsorbed on the
      modified surface at room temperature. This is evidenced by the formation of 1
      dimensional atomic chains (Pb, Al) attached to one side of the pre-adsorbed
      molecule. 

PMID- 26303775
TI  - Placebo Medication and Sham Surgery Responses in Benign Prostatic Hyperplasia
      Treatments: Implications for Clinical Trials.
AB  - Placebo medications and sham surgeries have long been thought to be inert
      treatments. These groups served as a threshold to which an active treatment
      should be compared in a randomized trial to determine the true efficacy of the
      active treatment. However, surprising changes in subjective symptom scores and
      objective measures of voiding have been demonstrated in numerous placebo
      medication or sham surgery arms of trials. The exact mechanisms by which these
      inactive treatments augment patient outcomes are not clearly defined and multiple
      theories have been proposed to explain the often pronounced response. It appears
      that urologic outcomes are particularly prone to these effects and the astute
      physician should keep these responses in mind when interpreting any trial on a
      new therapy. 

PMID- 26303776
TI  - Obesity, Physical Activity and Bladder Cancer.
AB  - While smoking and exposure to certain chemicals are well-defined risk factors for
      bladder cancer, there is no consensus as to the roles of modifiable lifestyle
      factors, notably physical activity, and obesity. We evaluated associations of
      obesity and physical activity with bladder cancer risk by performing a system
      wide search of PubMed for cohort and case-control studies focused on obesity,
      exercise, and bladder cancer. A total of 31 studies were identified that
      evaluated the associations of obesity and physical activity with bladder cancer
      risk: 20 focused on obesity, eight on physical activity, and three on both. There
      was marked heterogeneity in population composition and outcomes assessment.
      Fifteen (65%) of the obesity studies used prevalence or incidence as the primary
      outcome and seven (30%) used bladder cancer mortality. Ten (44%) observed
      positive and 13 (56%) null associations of obesity with bladder cancer. Three
      (100%) of three studies also noted strong positive associations of obesity with
      bladder cancer progression or recurrence. Ten (91%) of the physical activity
      studies analyzed prevalence or incidence and one (9%) mortality. One (9%) study
      observed positive, seven (64%) null, and three (27%) negative associations of
      physical activity with bladder cancer. Study heterogeneity precluded quantitative
      assessment of outcomes. Obesity is potentially associated with an increased risk
      of bladder cancer, particularly for progression, recurrence, or death. Further
      studies of physical activity and bladder cancer are needed to validate these
      observations and elucidate the associations of exercise with bladder cancer
      progression and mortality.

PMID- 26303778
TI  - Transplantation: Wide variation in rates of dialysis facility referrals to
      transplant centres.

PMID- 26303779
TI  - Renal physiology: Aldosterone-dependent NCC activation.

PMID- 26303777
TI  - Refining the pH response in Aspergillus nidulans: a modulatory triad involving
      PacX, a novel zinc binuclear cluster protein.
AB  - The Aspergillus nidulans PacC transcription factor mediates gene regulation in
      response to alkaline ambient pH which, signalled by the Pal pathway, results in
      the processing of PacC(72) to PacC(27) via PacC(53). Here we investigate two
      levels at which the pH regulatory system is transcriptionally moderated by pH and
      identify and characterise a new component of the pH regulatory machinery, PacX.
      Transcript level analysis and overexpression studies demonstrate that repression
      of acid-expressed palF, specifying the Pal pathway arrestin, probably by PacC(27)
      and/or PacC(53), prevents an escalating alkaline pH response. Transcript analyses
      using a reporter and constitutively expressed pacC trans-alleles show that pacC
      preferential alkaline-expression results from derepression by depletion of the
      acid-prevalent PacC(72) form. We additionally show that pacC repression requires
      PacX. pacX mutations suppress PacC processing recalcitrant mutations, in part,
      through derepressed PacC levels resulting in traces of PacC(27) formed by pH
      independent proteolysis. pacX was cloned by impala transposon mutagenesis. PacX,
      with homologues within the Leotiomyceta, has an unusual structure with an amino
      terminal coiled-coil and a carboxy-terminal zinc binuclear cluster. pacX
      mutations indicate the importance of these regions. One mutation, an
      unprecedented finding in A. nidulans genetics, resulted from an insertion of an
      endogenous Fot1-like transposon.

PMID- 26303780
TI  - Dietary milk fat globule membrane supplementation combined with regular exercise
      improves skeletal muscle strength in healthy adults: a randomized double-blind,
      placebo-controlled, crossover trial.
AB  - BACKGROUND: Our previous studies demonstrated that dietary supplementation with
      milk fat globule membrane (MFGM) combined with habitual exercise improved muscle
      strength by stimulating neuromuscular development in mice. This study aimed to
      demonstrate the beneficial effects of dietary MFGM supplementation plus regular
      exercise on muscle strength and neuromuscular function in healthy humans.
      METHODS: The study was designed as a randomized, double-blind, placebo
      controlled, crossover trial. Fourteen Japanese adults aged 31-48 years took daily
      MFGM (1 g) or placebo tablets during the 4-week study period and attended a
      training program twice a week. Physical function tests and surface
      electromyography (EMG) were conducted at baseline and at the end of the study
      period. RESULTS: The MFGM group had significantly greater leg extension strength
      than the placebo group after the 4-week study period. Surface EMG showed that the
      MFGM group had a significantly higher root mean square amplitude than the placebo
      group, which indicated that the MFGM group had higher motor unit activity.
      CONCLUSIONS: Dietary MFGM supplementation combined with regular exercise improves
      skeletal muscle strength, which may be due to increased motor unit recruitment in
      healthy Japanese middle-aged adults.

PMID- 26303781
TI  - A case of immediate type of food allergy due to parvalbumin from soft-shelled
      turtle (Trionychidae) occurring in the working environment.

PMID- 26303782
TI  - The Adipokine Chemerin Induces Apoptosis in Cardiomyocytes.
AB  - BACKGROUND: The adipokine chemerin has been associated with cardiovascular
      disease. We investigated the effects of chemerin on viability and intracellular
      signalling in murine cardiomyocytes, and the effects of insulin and TNF-alpha on
      cardiomyocyte chemerin production. METHODS: Hoechst dye vital staining and cell
      cycle analysis were used to analyse the viability of murine cardiac cells in
      culture. Western blot was used to explore the phosphorylation of AKT and caspase
      9 activity in neonatal rat cardiomyocytes and HL-1 cells. Finally, RT-qPCR, ELISA
      and western blot were performed to examine chemerin and CMKLR1 expression after
      insulin and TNF-alpha treatment in cardiac cells. RESULTS: Chemerin treatment
      increased apoptosis, reduced phosphorylation of AKT at Thr308 and increased
      caspase-9 activity in murine cardiomyocytes. Insulin treatment lowered chemerin
      and CMKLR1 mRNA and protein levels, and the amount of chemerin in the cell media,
      while TNF-alpha treatment increased chemerin mRNA and protein levels but
      decreased expression of the CMKLR1 gene. CONCLUSION: Chemerin induces apoptosis,
      reduces AKT phosphorylation and increases the cleavage of caspase-9 in murine
      cardiomyocytes. The expression of chemerin is regulated by important metabolic
      (insulin) and inflammatory (TNF-alpha) mediators at cardiac level. Our results
      suggest that chemerin could play a role in the physiopathology of cardiac
      diseases.

PMID- 26303783
TI  - Inguinal seroma prevention by reverse mapping using inodocyanine green
      lymphography.

PMID- 26303784
TI  - Esophageal morphometric and biomechanical changes during aging in rats.
AB  - BACKGROUND: Human studies have demonstrated aging-related changes in esophagus
      which may contribute to the increased rate of gastro-esophageal reflux in
      elderly. The aim of this study was to investigate esophageal morphometric and
      biomechanical remodeling in aging rats to obtain detailed information about aging
      related changes. METHODS: Twenty-four male Wistar rats, aged from 6 to 22 months,
      were studied. Morphometric data were obtained by measuring the wall thickness and
      cross-sectional area. The esophageal diameter and length were obtained from
      digitized images of the segments at preselected luminal pressure levels and at no
      load and zero-stress states. Circumferential and longitudinal stresses (force per
      area) and strains (deformation) were computed from the length, diameter and
      pressure data, and from the zero-stress state geometry. KEY RESULTS: The
      esophageal parameters such as the weight per unit length, the wall thickness and
      the wall cross-sectional area increased slightly from 6 to 22 months (p < 0.05 to
      p < 0.001). The opening angle gradually decreased during aging (p < 0.05). The
      interface between the mucosa-submucosa and muscle layers slightly moved outwards
      and the neutral axis moved inwards during aging. The stress-strain data showed
      that the esophageal wall became stiffer circumferentially and longitudinally
      during aging (p < 0.05, p < 0.01). However, the circumferential wall stiffness
      showed no further change after 12 months. CONCLUSIONS & INFERENCES: A pronounced
      morphometric and biomechanical remodeling occurred in the rat esophagus during
      aging.

PMID- 26303786
TI  - Immobilization and stretching of 5'-pyrene-terminated DNA on carbon film
      deposited on electron microscope grid.
AB  - The immobilization and stretching of randomly coiled DNA molecules on hydrophobic
      carbon film is a challenging microscopic technique, which possess various
      applications, especially for genome sequencing. In this report the pyrenyl
      nucleus is used as an anchor moiety to acquire higher affinity of double stranded
      DNA to the graphite surface. DNA and pyrene are joined through a linker composed
      of four aliphatic methylene groups. For the preparation of pyrene-terminated DNA
      a multifunctional phosphoramidite monomer compound was designed. It contains
      pyrenylbutoxy group as an anchor moiety for pi-stacking attachment to the carbon
      film, 2-cyanoethyloxy, and diisopropylamino as coupling groups for conjugation to
      activated oligonucleotide chain or DNA molecule. This monomer derivative was
      suitable for incorporation into automated solid-phase DNA synthesis and was
      attached to the 5' terminus of the DNA chain through a phosphodiester linkage.
      The successful immobilization and stretching of pyrene-terminated DNA was
      demonstrated by conventional 100 kV transmission electron microscope. The
      microscopic analysis confirmed the stretched shape of the negatively charged
      nucleic acid pieces on the hydrophobic carbon film.

PMID- 26303785
TI  - Tracing reinforcement through asymmetrical partner preference in the European
      common vole Microtus arvalis.
AB  - BACKGROUND: The mechanistic basis of speciation and in particular the
      contribution of behaviour to the completion of the speciation process is often
      contentious. Contact zones between related taxa provide a situation where
      selection against hybridization might reinforce separation by behavioural
      mechanisms, which could ultimately fully isolate the taxa. One of the most
      abundant European mammals, the common vole Microtus arvalis, forms multiple
      natural hybrid zones where rapidly diverging evolutionary lineages meet in
      secondary contact. Very narrow zones of hybridization spanning only a few
      kilometres and sex-specific gene flow patterns indicate reduced fitness of
      natural hybrids and incipient speciation between some of the evolutionary
      lineages. In this study, we examined the contribution of behavioural mechanisms
      to the speciation process in these rodents by fine-mapping allopatric and
      parapatric populations in the hybrid zone between the Western and Central
      lineages and experimental testing of the partner preferences of wild, pure-bred
      and hybrid female common voles. RESULTS: Genetic analysis based on microsatellite
      markers revealed the presence of multiple parapatric and largely non-admixed
      populations at distances of about 10 km at the edge of the area of natural
      hybridization between the Western and Central lineages. Wild females from Western
      parapatric populations and lab-born F1 hybrids preferred males from the Western
      lineage whereas wild females of Central parapatric origin showed no measurable
      preference. Furthermore, wild and lab-born females from allopatric populations of
      the Western or Central lineages showed no detectable preference for males from
      either lineage. CONCLUSIONS: The detected partner preferences are consistent with
      asymmetrical reinforcement of pre-mating reproductive isolation mechanisms in the
      European common vole and with earlier results suggesting that hybridization is
      more detrimental to the Western lineage. As a consequence, these differences in
      behaviour might contribute to a further geographical stabilization of this moving
      hybrid zone. Such behavioural processes could also provide a mechanistic
      perspective for frequently-detected asymmetrical introgression patterns in the
      largely allopatrically diversifying Microtus genus and other rapidly speciating
      rodents.

PMID- 26303788
TI  - Is Acute Carotid Artery Stent Thrombosis an Avoidable Complication?
AB  - The most serious complication of carotid artery stenting (CAS) is acute carotid
      artery stent thrombosis (ACAST). ACAST is a very rare complication, but it may
      lead to dramatic and catastrophic consequences. The most important cause is
      inadequate or ineffective antiaggregant therapy. It is very important to
      identify, before CAS, those patients who might be candidates for ACAST and to
      start antiplatelet therapy for them. Testing patients who are candidates for CAS
      for acetylsalicylic acid and clopidogrel resistance may prevent this
      complication. 

PMID- 26303787
TI  - Higher Treadmill Training Intensity to Address Functional Aerobic Impairment
      after Stroke.
AB  - BACKGROUND: Peak aerobic capacity (VO2 peak) is severely worsened after disabling
      stroke, having serious implications for function, metabolism, and ongoing
      cardiovascular risk. Work from our laboratory and others has previously shown
      that modest improvements in VO2 peak are possible in stroke participants with
      aerobic exercise training. The purpose of the current investigation was to test
      the extent to which greater enhancements in VO2 peak after stroke are possible
      using a treadmill protocol with far greater emphasis on intensity progression
      compared with a protocol without such emphasis. METHODS: Using a randomized
      design, we compared stroke survivors engaged in higher intensity treadmill
      training (HI-TM, 80% heart rate reserve [HRR]) with those undergoing lower
      intensity treadmill training (LO-TM, 50% HRR). Measured outcomes were change in
      VO2 peak, 6-minute walk distance (6MWD), 30-ft walk times (30WT), and 48-hour
      step counts (48SC). LO-TM participants trained for a longer period of time per
      session in an effort to approximately match workload/caloric expenditure.
      Participants were randomized with stratification according to age and baseline
      walking capacity. RESULTS: HI-TM participants (n = 18) had significantly greater
      gains in VO2 peak (+34%) than LO-TM participants (n = 16; +5%) across the 6-month
      intervention period (P = .001, group * time interaction). Conversely, there was
      no statistical difference between groups in the changes observed for 6MWD, 30WT,
      or 48SC. CONCLUSIONS: HI-TM is far more effective than LO-TM for improving VO2
      peak after disabling stroke. The magnitude of relative improvement for HI-TM was
      double compared with previous reports from our laboratory with probable clinical
      significance for this population.

PMID- 26303789
TI  - Inpatient Statin Use Is Associated with Decreased Mortality of Acute Stroke
      Patients with Very Low Low-Density Lipoprotein Cholesterol.
AB  - BACKGROUND: To investigate the potential benefits of inpatient statin therapy on
      mortality of acute stroke patients with very low admission low-density
      lipoprotein cholesterol (LDL-C) level (<1.81 mmol/L). METHODS: The acute stroke
      patients with admission LDL-C level less than 1.81 mmol/L were enrolled from the
      China National Stroke Registry. The patients were divided into statin group and
      non-statin group during hospitalization. The association between statin therapy
      and mortality of participants in 1 year was analyzed by multivariable binary
      logistic regression models. RESULTS: A total of 1018 patients were enrolled, and
      the cumulative mortality rate was 10.1% at 3 months, 13.1% at 6 months, and 15.9
      % at 1 year. The all-cause mortality rate in statin group was significantly lower
      than that in non-statin group (3.6% versus 13.7% at 3 months, P < .001; 6.2%
      versus 16.9% at 6 months, P < .001; 8.4% versus 20% at 1 year, P < .001). The
      logistic analyses showed that statin therapy during hospitalization was
      independently associated with decreased mortality at 3 months (odds ratio [OR],
      .35; 95% confidence interval [CI], .18-.67), at 6 months (OR, .42; 95% CI, .25
      .73) and at 1 year (OR, .47; 95% CI, .29-.76). CONCLUSIONS: Statin use during
      hospitalization could decrease mortality of acute ischemic stroke patients with
      very low admission LDL-C.

PMID- 26303790
TI  - Acute Amnesia due to Isolated Mammillary Body Infarct.
AB  - BACKGROUND: There are limited reports describing acute amnesia after
      mammillothalamic tract infarction. Furthermore, acute infarction isolated to the
      mammillary body has never been reported. We present the first case of anterograde
      amnesia after isolated acute infarction of the mammillary body in a patient
      without concurrent or prior thalamic or mammillothalamic tract injury. METHODS: A
      retrospective review of the patient's electronic medical record including
      inpatient notes and all radiological examinations was performed. RESULTS: A 50
      year-old woman presented with acute onset of confusion and constant repetition of
      the same questions. Magnetic resonance (MR) imaging of the brain showed isolated
      acute infarct of the left mammillary body without concurrent abnormality of the
      thalamus or mammillothalamic tract. MR angiography showed severe stenosis of the
      proximal posterior cerebral artery at the origin of the perforating mammillary
      artery. CONCLUSIONS: Isolated injury to the mammillary body is rare. In addition
      to recognized memory-related structures such as the thalamus and mammillothalamic
      tract, mammillary body injury may also play a role in memory dysfunction.
      Knowledge of the vascular supply of memory-related structures is important in
      diagnosing and understanding memory dysfunction.

PMID- 26303791
TI  - Clopidogrel Resistance after Minor Ischemic Stroke or Transient Ischemic Attack
      is Associated with Radiological Cerebral Small-Vessel Disease.
AB  - BACKGROUND: The objective of this study was to compare nonresponders (NR) and
      responders (R) to clopidogrel with respect to presence of microvascular and
      macrovascular pathology in a cohort of patients with recent minor ischemic stroke
      (IS) or transient ischemic attack (TIA). METHODS: Seventy-two patients treated
      with clopidogrel after IS or TIA were evaluated 1 month after onset. Platelet
      aggregation was measured by multiple electrode aggregometry (Multiplate).
      Nonresponse was defined according to recent consensus. The degree of cerebral
      small-vessel disease (cSVD) was evaluated on computed tomography scans of the
      brain using Fazekas scale for white matter changes. Carotid atherosclerosis was
      evaluated by ultrasound or computed tomography/magnetic resonance angiography.
      RESULTS: Twenty-two percent of patients were NR. Moderate to extensive cSVD was
      more common for NR than R, 56% versus 25%, odds ratio 3.9 (1.2-12), P = .03.
      Correspondingly, 39% of patients with cSVD were NR versus 14% of patients with no
      or mild cSVD. No differences were found between NR and R in prevalence or
      severity of carotid atherosclerosis. NR had higher platelet aggregation response
      than R after stimulation with arachidonic acid or thrombin receptor-activating
      peptide, indicating a general platelet hyperreactivity. In a univariate analysis,
      hypertension, previous IS, glucose intolerance, pulse pressure above median, and
      presence of moderate to extensive cSVD were associated with the NR phenotype.
      CONCLUSIONS: Nonresponsiveness to clopidogrel after minor IS or TIA is associated
      with radiological cSVD but not with carotid atherosclerosis.
      PRACTICE/IMPLICATIONS: Measurement of platelet function is warranted in patients
      with cSVD. Larger studies on alternative or tailored antiplatelet treatment for
      these patients should be initiated.

PMID- 26303792
TI  - The Use of Nintendo Wii in the Rehabilitation of Poststroke Patients: A
      Systematic Review.
AB  - BACKGROUND: To evaluate the effectiveness of the video game console Nintendo Wii
      (NW) in motor function, balance, and functional independence in the treatment of
      poststroke patients and to identify which games are commonly used in therapy.
      METHODS: Randomized controlled trials were researched in MEDLINE, Cochrane
      Library, PEDro, CAPES Periodic, BIREME, and LILACS databases, covering
      publications up to March 31, 2014. The assessment of methodological quality was
      performed using the PEDro Scale as reference. RESULTS: The 5 studies included for
      analysis showed that NW can provide an improvement of motor function of the
      individual, but the data are unclear when it comes to the balance and functional
      independence. CONCLUSIONS: It was concluded that there is little evidence to
      ensure the effectiveness and support the inclusion of the treatment with NW in
      patients with sequelae caused by a stroke; however, some of the studies analyzed
      suggest that NW can provide improvement in motor function.

PMID- 26303793
TI  - A case of chronic suppurative otitis media caused by Kerstersia gyiorum.
AB  - Chronic suppurative otitis media is inflammation of the middle ear and mastoid
      that involves discharge and hearing loss. Kerstersia gyiorum is a member of the
      Alcaligenaceae family that who could not be treated with classical treatments
      such as patients with chronic otitis media, neck abscesses. K. gyiorum strain
      isolated from a patient with chronic suppurative otitis media. 

PMID- 26303794
TI  - Impact of arterial input function selection on the accuracy of dynamic contrast
      enhanced MRI quantitative analysis for the diagnosis of clinically significant
      prostate cancer.
AB  - PURPOSE: Using a limited temporal resolution dynamic contrast-enhanced (DCE)
      magnetic resonance imaging (MRI) dataset to assess the impact of the arterial
      input function (AIF) choice on the transfer constant (K(trans) ) to distinguish
      prostate carcinoma (PCa) from benign tissue. MATERIALS AND METHODS: Thirty-eight
      patients with clinically important peripheral PCa (>=0.5 cc) were retrospectively
      studied. These patients underwent 1.5T multiparametric prostate MR with PCa and
      benign regions of interest (ROIs) selected using a visual registration with
      morphometric reconstruction obtained from radical prostatectomy. Using three
      pharmacokinetic (PK) analysis software programs, the mean K(trans) of ROIs was
      computed using three AIFs: an individual AIF (Ind-AIF) and two literature
      population average AIFs of Weinmann (W-AIF) and of Fritz-Hansen (FH-AIF). A
      pairwise comparison of the area under the receiver operating characteristic
      curves (AUROCC) obtained with different AIFs was performed. RESULTS: AUROCCs
      obtained with W-AIF (ranging from 0.801 to 0.843) were significantly higher than
      FH-AIF (ranging from 0.698 to 0.780, 0.002 <= P <= 0.045) and similar to or
      higher than Ind-AIF (ranging from 0.591 to 0.839, 0.014 <= P <= 0.9). Ind-AIF and
      FH-AIF provided similar AUROCC (0.34 <= P <= 0.81). The pairwise correlation of
      K(trans) values was moderate to very strong when comparing W-AIF with FH-AIF (the
      Spearman's correlation coefficients [SCCs] ranged from 0.55 to 0.93) and very
      weak to moderate when comparing W-AIF with Ind-AIF (the SCCs ranged from 0.018 to
      0.59) or FH-AIF with Ind-AIF (the SCCs ranged from 0.30 to 0.51). CONCLUSION: W
      AIF yielded a higher performance than FH-AIF and a similar or higher performance
      than Ind-AIF in distinguishing PCa from benign tissue.

PMID- 26303795
TI  - Susceptibility of Mycobacterium abscessus to antimycobacterial drugs in
      preclinical models.
AB  - Over the last 10 years, Mycobacterium abscessus group strains have emerged as
      important human pathogens, which are associated with significantly higher
      fatality rates than any other rapidly growing mycobacteria. These opportunistic
      pathogens are widespread in the environment and can cause a wide range of
      clinical diseases, including skin, soft tissue, central nervous system, and
      disseminated infections; by far, the most difficult to treat is the pulmonary
      form. Infections with M. abscessus are often multidrug-resistant (MDR) and
      require prolonged treatment with various regimens and, many times, result in high
      mortality despite maximal therapy. We report here the evaluation of diverse mouse
      infection models for their ability to produce a progressive high level of
      infection with M. abscessus. The nude (nu/nu), SCID (severe combined
      immunodeficiency), gamma interferon knockout (GKO), and granulocyte-macrophage
      colony-stimulating factor (GMCSF) knockout mice fulfilled the criteria for an
      optimal model for compound screening. Thus, we set out to assess the
      antimycobacterial activity of clarithromycin, clofazimine, bedaquiline, and
      clofazimine-bedaquiline combinations against M. abscessus-infected GKO and SCID
      murine infection models. Treatment of GKO and SCID mice with a combination of
      clofazimine and bedaquiline was the most effective in decreasing the M. abscessus
      organ burden. 

PMID- 26303796
TI  - Antibiofilm and membrane-damaging potential of cuprous oxide nanoparticles
      against Staphylococcus aureus with reduced susceptibility to vancomycin.
AB  - The antimicrobial effects of copper ions and salts are well known, but the
      effects of cuprous oxide nanoparticles (Cu2O-NPs) on staphylococcal biofilms have
      not yet been clearly revealed. The present study evaluated Cu2O-NPs for their
      antibacterial and antibiofilm activities against heterogeneous vancomycin
      intermediate Staphylococcus aureus (hVISA) and vancomycin-intermediate S. aureus
      (VISA). Nanoscaled Cu2O, generated by solution phase technology, contained Cu2O
      octahedral nanoparticles. Field emission electron microscopy demonstrated
      particles with sizes ranging from 100 to 150 nm. Cu2O-NPs inhibited the growth of
      S. aureus and showed antibiofilm activity. The MICs and minimum biofilm
      inhibitory concentrations ranged from 625 MUg/ml to 5,000 MUg/ml and from 2,500
      MUg/ml to 10,000 MUg/ml, respectively. Exposure of S. aureus to Cu2O-NPs caused
      leakage of the cellular constituents and increased uptake of ethidium bromide and
      propidium iodide. Exposure also caused a significant reduction in the overall
      vancomycin-BODIPY (dipyrromethene boron difluoride [4,4-difluoro-4-bora-3a,4a
      diaza-s-indacene] fluorescent dye) binding and a decrease in the viable cell
      count in the presence of 7.5% sodium chloride. Cu2O-NP toxicity assessment by
      hemolysis assay showed no cytotoxicity at 625 to 10,000 MUg/ml concentrations.
      The results suggest that Cu2O-NPs exert their action by disruption of the
      bacterial cell membrane and can be used as effective antistaphylococcal and
      antibiofilm agents in diverse medical devices. 

PMID- 26303797
TI  - In vitro interactions of antifungal agents and tacrolimus against Aspergillus
      biofilms.
AB  - Aspergillus biofilms were prepared from Aspergillus fumigatus, Aspergillus
      flavus, and Aspergillus terreus via a 96-well plate-based method, and the
      combined antifungal activity of tacrolimus with azoles or amphotericin B against
      Aspergillus biofilms was investigated via a broth microdilution checkerboard
      technique system. Our results suggest that combinations of tacrolimus with
      voriconazole or amphotericin B have synergistic inhibitory activity against
      Aspergillus biofilms. However, combinations of tacrolimus with itraconazole or
      posaconazole exhibit no synergistic or antagonistic effects. 

PMID- 26303798
TI  - Dissemination of carbapenemase-producing Enterobacteriaceae and Pseudomonas
      aeruginosa in Romania.
AB  - Fifteen carbapenemase-producing Enterobacteriaceae isolates and 12 carbapenemase
      producing Pseudomonas aeruginosa isolates were recovered from patients
      hospitalized between August 2011 and March 2013 at the Hospital of Infectious
      Disease, Cluj-Napoca, Romania. One KPC-, nine NDM-1-, four OXA-48-, and one VIM-4
      producing Enterobacteriaceae isolates along with 11 VIM-2-producing and one IMP
      13-producing P. aeruginosa isolates were recovered from clinical samples. All
      carbapenemase genes were located on self-conjugative plasmids and were associated
      with other resistance determinants, including extended-spectrum beta-lactamases
      and RmtC methylases. 

PMID- 26303799
TI  - Novel insights into the molecular events linking to cell death induced by
      tetracycline in the amitochondriate protozoan Trichomonas vaginalis.
AB  - Trichomonas vaginalis colonizes the human urogenital tract and causes
      trichomoniasis, the most common nonviral sexually transmitted disease. Currently,
      5-nitroimidazoles are the only recommended drugs for treating trichomoniasis.
      However, increased resistance of the parasite to 5-nitroimidazoles has emerged as
      a highly problematic public health issue. Hence, it is essential to identify
      alternative chemotherapeutic agents against refractory trichomoniasis.
      Tetracycline (TET) is a broad-spectrum antibiotic with activity against several
      protozoan parasites, but the mode of action of TET in parasites remains poorly
      understood. The in vitro effect of TET on the growth of T. vaginalis was
      examined, and the mode of cell death was verified by various apoptosis-related
      assays. Next-generation sequencing-based RNA sequencing (RNA-seq) was employed to
      elucidate the transcriptome of T. vaginalis in response to TET. We show that TET
      has a cytotoxic effect on both metronidazole (MTZ)-sensitive and -resistant T.
      vaginalis isolates, inducing some features resembling apoptosis. RNA-seq data
      reveal that TET significantly alters the transcriptome via activation of specific
      pathways, such as aminoacyl-tRNA synthetases and carbohydrate metabolism.
      Functional analyses demonstrate that TET disrupts the hydrogenosomal membrane
      potential and antioxidant system, which concomitantly elicits a metabolic shift
      toward glycolysis, suggesting that the hydrogenosomal function is impaired and
      triggers cell death. Collectively, we provide in vitro evidence that TET is a
      potential alternative therapeutic choice for treating MTZ-resistant T. vaginalis.
      The in-depth transcriptomic signatures in T. vaginalis upon TET treatment
      presented here will shed light on the signaling pathways linking to cell death in
      amitochondriate organisms. 

PMID- 26303800
TI  - Role of urine neutrophil gelatinase-associated lipocalin in the early diagnosis
      of amphotericin B-induced acute kidney injury.
AB  - Determination of the neutrophil gelatinase-associated lipocalin (NGAL) level can
      be used to detect acute kidney injury (AKI) earlier than determination of the
      serum creatinine (SCr) level in settings such as cardiac surgery, contrast
      nephropathy, and intensive care units. We hypothesized that urine NGAL (UrNGAL)
      would be an early biomarker of drug nephrotoxicity. To test this, we studied
      hemodynamically stable patients treated with amphotericin B (AmB). We measured
      the SCr and UrNGAL levels at the baseline and daily after initiation of AmB up to
      day 14 or development of AKI by the use of the SCr criterion. AKI was defined
      according to a Kidney Disease: Improving Global Outcomes (KDIGO) criterion (an
      increase in the SCr level by >=0.3 mg/dl within 48 h or an SCr level >=1.5 times
      the baseline level within 7 days). We studied 24 patients with a mean age of 48.4
      +/- 16.4 years. Most patients were male, and the patients received AmB (12
      received AmB deoxycholate and 12 received liposomal AmB) for the treatment of
      leishmaniasis (91.7%). Overall, 17/24 patients fulfilled a KDIGO criterion for
      AKI. Peak UrNGAL levels were higher in patients with AKI than in patients without
      AKI and in recipients of AmB deoxycholate than in recipients of liposomal AmB.
      The diagnostic performance of the UrNGAL level on day 5 for the detection of AKI
      was moderate, with the area under the curve (AUC) being 0.68 (95% confidence
      interval [CI], 0.41 to 0.95). In the subgroup receiving AmB deoxycholate,
      however, the AUC rose to 0.89 (95% CI, 0.67 to 1.00). In a patient-level
      analysis, we found that AKI could be detected 3.2 days earlier by the use of the
      UrNGAL criterion than by the use of the SCr criterion (times to AKI by the UrNGAL
      and SCr criteria, 3.7 +/- 2.5 versus 6.9 +/- 3.3 days, respectively; P = 0.001).
      Future studies should evaluate if a treatment strategy oriented toward evaluation
      of UrNGAL levels will improve outcomes. These findings for AmB-induced AKI in
      leishmaniasis patients could serve as a basis for the investigation of urine
      biomarkers in the early detection of drug nephrotoxicity in other clinical
      settings. 

PMID- 26303801
TI  - Susceptibilities of genotype 1a, 1b, and 3 hepatitis C virus variants to the NS5A
      inhibitor elbasvir.
AB  - Elbasvir is an investigational NS5A inhibitor with in vitro activity against
      multiple HCV genotypes. Antiviral activity of elbasvir was measured in replicons
      derived from wild-type or resistant variants of genotypes 1a, 1b, and 3. The
      barrier to resistance was assessed by the number of resistant colonies selected
      by exposure to various elbasvir concentrations. In a phase 1b dose-escalating
      study, virologic responses were determined in 48 noncirrhotic adult men with
      chronic genotype 1 or 3 infections randomized to placebo or elbasvir from 5 to 50
      mg (genotype 1) or 10 to 100 mg (genotype 3) once daily for 5 days. The NS5A gene
      was sequenced from plasma specimens obtained before, during, and after treatment.
      Elbasvir suppressed the emergence of resistance-associated variants (RAVs) in
      vitro in a dose-dependent manner. Variants selected by exposure to high elbasvir
      concentrations typically encoded multiple amino acid substitutions (most commonly
      involving loci 30, 31, and 93), conferring high-level elbasvir resistance. In the
      monotherapy study, patients with genotype 1b had greater reductions in HCV RNA
      levels than patients with genotype 1a at all elbasvir doses; responses in
      patients with genotype 3 were generally less pronounced than for genotype 1,
      particularly at lower elbasvir doses. M28T, Q30R, L31V, and Y93H in genotype 1a,
      L31V and Y93H in genotype 1b, and A30K, L31F, and Y93H in genotype 3 were the
      predominant RAVs selected by elbasvir monotherapy. Virologic findings in patients
      were consistent with the preclinical observations. NS5A-RAVs emerged most often
      at amino acid positions 28, 30, 31, and 93 in both the laboratory and clinical
      trial. (The MK-8742 P002 trial has been registered at ClinicalTrials.gov under
      identifier NCT01532973.). 

PMID- 26303802
TI  - Mutation of Rv2887, a marR-like gene, confers Mycobacterium tuberculosis
      resistance to an imidazopyridine-based agent.
AB  - Drug resistance is a major problem in Mycobacterium tuberculosis control, and it
      is critical to identify novel drug targets and new antimycobacterial compounds.
      We have previously identified an imidazo[1,2-a]pyridine-4-carbonitrile-based
      agent, MP-III-71, with strong activity against M. tuberculosis. In this study, we
      evaluated mechanisms of resistance to MP-III-71. We derived three independent M.
      tuberculosis mutants resistant to MP-III-71 and conducted whole-genome sequencing
      of these mutants. Loss-of-function mutations in Rv2887 were common to all three
      MP-III-71-resistant mutants, and we confirmed the role of Rv2887 as a gene
      required for MP-III-71 susceptibility using complementation. The Rv2887 protein
      was previously unannotated, but domain and homology analyses suggested it to be a
      transcriptional regulator in the MarR (multiple antibiotic resistance repressor)
      family, a group of proteins first identified in Escherichia coli to negatively
      regulate efflux pumps and other mechanisms of multidrug resistance. We found that
      two efflux pump inhibitors, verapamil and chlorpromazine, potentiate the action
      of MP-III-71 and that mutation of Rv2887 abrogates their activity. We also used
      transcriptome sequencing (RNA-seq) to identify genes which are differentially
      expressed in the presence and absence of a functional Rv2887 protein. We found
      that genes involved in benzoquinone and menaquinone biosynthesis were repressed
      by functional Rv2887. Thus, inactivating mutations of Rv2887, encoding a putative
      MarR-like transcriptional regulator, confer resistance to MP-III-71, an effective
      antimycobacterial compound that shows no cross-resistance to existing
      antituberculosis drugs. The mechanism of resistance of M. tuberculosis Rv2887
      mutants may involve efflux pump upregulation and also drug methylation. 

PMID- 26303803
TI  - Guanabenz repurposed as an antiparasitic with activity against acute and latent
      toxoplasmosis.
AB  - Toxoplasma gondii is a protozoan parasite that persists as a chronic infection.
      Toxoplasma evades immunity by forming tissue cysts, which reactivate to cause
      life-threatening disease during immune suppression. There is an urgent need to
      identify drugs capable of targeting these latent tissue cysts, which tend to form
      in the brain. We previously showed that translational control is critical during
      infections with both replicative and latent forms of Toxoplasma. Here we report
      that guanabenz, an FDA-approved drug that interferes with translational control,
      has antiparasitic activity against replicative stages of Toxoplasma and the
      related apicomplexan parasite Plasmodium falciparum (a malaria agent). We also
      found that inhibition of translational control interfered with tissue cyst
      biology in vitro. Toxoplasma bradyzoites present in these abnormal cysts were
      diminished and misconfigured, surrounded by empty space not seen in normal cysts.
      These findings prompted analysis of the efficacy of guanabenz in vivo by using
      established mouse models of acute and chronic toxoplasmosis. In addition to
      protecting mice from lethal doses of Toxoplasma, guanabenz has a remarkable
      ability to reduce the number of brain cysts in chronically infected mice. Our
      findings suggest that guanabenz can be repurposed into an effective antiparasitic
      with a unique ability to reduce tissue cysts in the brain. 

PMID- 26303804
TI  - Sensititre MycoTB plate compared to Bactec MGIT 960 for first- and second-line
      antituberculosis drug susceptibility testing in Tanzania: a call to
      operationalize MICs.
AB  - MIC testing for Mycobacterium tuberculosis is now commercially available. Drug
      susceptibility testing by the MycoTB MIC plate has not been directly compared to
      that by the Bactec MGIT 960. We describe a case of extensively drug-resistant
      tuberculosis (XDR-TB) in Tanzania where initial MIC testing may have prevented
      acquired resistance. From testing on archived isolates, the accuracy with the
      MycoTB plate was >90% for important first- and second-line drugs compared to that
      with the MGIT 960, and clinically useful quantitative interpretation was also
      provided. 

PMID- 26303805
TI  - Efficacy of a novel sublingual spray formulation of artemether in African
      children with Plasmodium falciparum malaria.
AB  - The efficacy of sublingual artemether (ArTiMist) was investigated in two studies.
      In study 1, 31 children were randomized to sublingual artemether (n = 16) or
      intravenous (i.v.) quinine (n = 15). In study 2, 151 children were randomized to
      sublingual artemether (n = 77) or i.v. quinine (n = 74). For both studies,
      patients weighed between 5 and 15 kg and had either severe or complicated malaria
      based on WHO criteria, or they had uncomplicated malaria but were unable to
      tolerate oral medication as a result of nausea, vomiting, or diarrhea. Patients
      received either 3 mg/kg of body weight of sublingual artemether or a loading dose
      of 20 mg/kg of i.v. quinine followed by 10 mg/kg every 8 h i.v. thereafter. The
      primary endpoint was parasitological success, defined as a reduction in parasite
      count of >=90% of that at baseline at 24 h after the first dose. Other endpoints
      based on parasite clearance and clinical response were evaluated. In study 1,
      there were parasitological success rates of 93.3% (14/15) and 66.7% (10/15) for
      the sublingual artemether and quinine treatments, respectively. In study 2, 94.3%
      (66/70) of the ArTiMist-treated patients and 39.4% (28/71) of the quinine-treated
      patients had parasitological success (P < 0.0001). Indicators of parasite
      clearance (parasite clearance time [PCT], time for parasite count to fall by 50%
      [PCT50], time for parasite count to fall by 90% [PCT90], and percent reduction in
      parasitemia from baseline at 24 h [PRR24]) were significantly superior for
      children treated with sublingual artemether compared to those treated with i.v.
      quinine. There were no differences between treatments for the clinical endpoints,
      such as fever clearance time. The local tolerability of sublingual artemether was
      good. Sublingual artemether leads to rapid parasite clearance and clinical
      recovery. (Studies 1 and 2 are registered at ClinicalTrials.gov under
      registration numbers NCT01047436 and NCT01258049, respectively.). 

PMID- 26303806
TI  - Risks associated with red blood cell transfusions: potential benefits from
      application of pathogen inactivation.
AB  - BACKGROUND: Red blood cell (RBC) transfusion risks could be reduced if a robust
      technology for pathogen inactivation of RBC (PI-RBCs) were to be approved.
      MATERIALS AND METHODS: Estimates of per-unit and per-patient aggregate infectious
      risks for conventional RBCs were calculated; the latter used patient diagnosis as
      a determinant of estimated lifetime exposure to RBC units. Existing in vitro data
      for the two technologies under development for producing PI-RBCs and the status
      of current clinical trials are reviewed. RESULTS: Minimum and maximum per-unit
      risk were calculated as 0.0003% (1 in 323,000) and 0.12% (1 in 831),
      respectively. The minimum estimate is for known lower-risk pathogens while the
      maximal estimate also includes an emerging infectious agent (EIA) and endemic
      area Babesia risk. Minimum and maximum per-patient lifetime risks by diagnosis
      grouping were estimated as 1.5 and 3.3%, respectively, for stem cell
      transplantation (which includes additional risk for cytomegalovirus
      transmission); 1.2 and 3.7%, respectively, for myelodysplastic syndrome; and 0.2
      and 44%, respectively, for hemoglobinopathy. DISCUSSION: There is potential for
      PI technologies to reduce infectious RBC risk and to provide additional benefits
      (e.g., prevention of transfusion-associated graft-versus-host disease and
      possible reduction of alloimmunization) due to white blood cell inactivation. PI
      RBCs should be viewed in the context of having a fully PI-treated blood supply,
      enabling a blood safety paradigm shift from reactive to proactive. Providing
      insurance against new EIAs. Further, when approved, the use of PI for all
      components may catalyze operational changes in blood donor screening, laboratory
      testing, and component manufacturing.

PMID- 26303807
TI  - SPAD-based leaf nitrogen estimation is impacted by environmental factors and crop
      leaf characteristics.
AB  - Chlorophyll meters are widely used to guide nitrogen (N) management by monitoring
      leaf N status in agricultural systems, but the effects of environmental factors
      and leaf characteristics on leaf N estimations are still unclear. In the present
      study, we estimated the relationships among SPAD readings, chlorophyll content
      and leaf N content per leaf area for seven species grown in multiple
      environments. There were similar relationships between SPAD readings and
      chlorophyll content per leaf area for the species groups, but the relationship
      between chlorophyll content and leaf N content per leaf area, and the
      relationship between SPAD readings and leaf N content per leaf area varied widely
      among the species groups. A significant impact of light-dependent chloroplast
      movement on SPAD readings was observed under low leaf N supplementation in both
      rice and soybean but not under high N supplementation. Furthermore, the
      allocation of leaf N to chlorophyll was strongly influenced by short-term changes
      in growth light. We demonstrate that the relationship between SPAD readings and
      leaf N content per leaf area is profoundly affected by environmental factors and
      leaf features of crop species, which should be accounted for when using a
      chlorophyll meter to guide N management in agricultural systems. 

PMID- 26303808
TI  - Newly born low birthweight infants stabilise better in skin-to-skin contact than
      when separated from their mothers: a randomised controlled trial.
AB  - AIM: Routine care of low birthweight (LBW) neonates relies on incubators for
      stabilisation. An earlier study suggested that skin-to-skin contact achieves
      better physiological stability in the transition period when compared to
      incubator care. The aim of this study was to replicate that study with a larger
      sample. METHODS: A randomised controlled trial with LBW infants (1500-2500 g)
      randomised at birth, 50 to routine care and 50 to skin-to-skin contact, with
      stabilisation using the Stability of Cardio-Respiratory system in Preterms
      (SCRIP) score measured repeatedly over the first six hours of life as the primary
      outcome. RESULTS: Newly born infants in skin-to-skin contact showed better
      transition to extra-uterine life (p < 0.02), with the SCRIP score at 360 minutes
      in skin-to-skin contact being 5.82 (SD 0.66) and in maternal infant separation
      5.24 (SD 0.72), p < 0.0001. In extended skin-to-skin contact care, infants had
      significantly less need for respiratory support, intravenous fluids and
      antibiotic use during the remainder of the hospital stay. CONCLUSION: Skin-to
      skin contact was likely to be an optimal environment for neonates without life
      threatening conditions who weighed 1500-2500 g at birth. By preventing
      instability that requires subsequent medical treatment, it may be life-saving in
      low-income countries.

PMID- 26303809
TI  - Ruxolitinib is an effective treatment for CALR-positive patients with
      myelofibrosis.

PMID- 26303810
TI  - Usability and acceptability of balance exergames in older adults: A scoping
      review.
AB  - Serious games (exergames) have the potential to be effective for postural balance
      and increasing muscle strength. Several games have been developed to increase
      physical fitness and balance among older adults. However, it is unclear to which
      degree usability and acceptability of exergames for older adults have been
      evaluated. The aim of this study was to summarize usability evaluation and
      acceptability of studies in older adults. We conducted a scoping review on
      studies focusing on usability of exergames for older adults. The result shows
      that older adults consider usability and acceptability of exercise video games
      good. The review shows that longitudinal studies mainly use off-the-shelf
      exergame and evaluated game effectiveness and acceptability, whereas cross
      sectional studies focus on interactional experience. Studies varied in their
      approaches to measure usability and acceptability of exergames for older adults.
      There is a need for a systematic developmental approach to involve older adults
      in development of exergames for longitudinal studies.

PMID- 26303811
TI  - Pancreatic cancer patients with lymph node involvement by direct tumor extension
      have similar survival to those with node-negative disease.
AB  - BACKGROUND: Lymph node (LN) involvement is a well-known poor prognostic factor in
      patients with pancreatic ductal adenocarcinoma (PDAC). However, there have been
      conflicting results on the significance of the mechanism of LN involvement,
      "direct" tumor invasion versus "metastatic," disease on patient survival.
      METHODS: Clinicopathologic records from all patients who underwent resection for
      PDAC from 1990 to 2014 at a single-institution were reviewed. RESULTS: Of the 385
      total patients, there was tumor invasion outside of the pancreas in 289 (75.1%)
      patients. Overall, 239 (62.1%) had node-positive disease: 220 (92.0%) by
      "metastatic" involvement, 14 (5.9%) by "direct" tumor extension, and five (2.1%)
      by a mix of "metastatic" and "direct". There were no significant differences in
      clinicopathologic factors associated with PDAC survival between "metastatic" and
      "direct" LN patients. The median overall survival for the whole cohort was 31.1
      months. Compared to overall survival in patients with LN-negative disease (median
      40.7 months), those with LNs involved by "metastatic" spread was significantly
      shorter (median 25.7 months, P < 0.001), yet "direct" LN extension was similar
      (median 48.1 months, P = 0.719). CONCLUSIONS: The mechanism of LN involvement
      affects PDAC prognosis. Patients with LNs involved by direct extension have
      similar survival to those with node-negative disease.

PMID- 26303812
TI  - Missing an opportunity: the embedded nature of weight management in primary care.
AB  - The 5As Team study was designed to create, implement and evaluate a flexible
      intervention to improve the quality and quantity of weight management visits in
      primary care. The objective of this portion of the study was to explore how
      primary care providers incorporate weight management in their practice. 5AsT is a
      randomized controlled trial (RCT) on the implementation of a 6-month 5 As Team
      (5AsT) intervention designed to operationalize the 5As of obesity management in
      primary care. Data for the qualitative portion of the study presented here
      included semi-structured interviews with 29 multidisciplinary team providers and
      field notes of intervention sessions. Thematic analysis was undertaken. A key
      pattern that emerged from the data was that healthcare providers usually do not
      address obesity as a primary focus for a visit. Rather, obesity is embedded in a
      wide range of primary care encounters for other conditions. Implications were it
      can take extra time to discuss weight, it can be inappropriate to bring up weight
      as a topic, and treating risk factors and root causes of obesity have indirect
      benefits to patient weight management. Our findings have implications for obesity
      treatment approaches and tools that assume a discreet weight management visit.
      The embedded nature of obesity management in primary care can be harnessed to
      leverage multiple opportunities for asking and assessing root causes of obesity,
      and working longitudinally towards individual health goals. 

PMID- 26303814
TI  - Clostridium perfringensalpha-toxin interaction with red cells and model
      membranes.
AB  - The effects of Clostridium perfringensalpha-toxin on host cells have previously
      been studied extensively but the biophysical processes associated with toxicity
      are poorly understood. The work reported here shows that the initial interaction
      between the toxin and lipid membrane leads to measurable changes in the physical
      properties and morphology of the membrane. A Langmuir monolayer technique was
      used to assess the response of different lipid species to toxin. Sphingomyelin
      and unsaturated phosphatidylcholine showed the highest susceptibility to toxin
      lypolitic action, with a two stage response to the toxin (an initial, rapid
      hydrolysis stage followed by the insertion and/or reorganisation of material in
      the monolayer). Fluorescence confocal microscopy on unsaturated
      phosphatidylcholine vesicles shows that the toxin initially aggregates at
      discrete sites followed by the formation of localised "droplets" accumulating the
      hydrolysis products. This process is accompanied by local increases in the
      membrane dipole potential by about 50 (+/-42) mV. In contrast, red blood cells
      incubated with the toxin suffered a decrease of the membrane dipole potential by
      50 (+/-40) mV in areas of high toxin activity (equivalent to a change in electric
      field strength of 10(7) V m(-1)) which is sufficient to affect the functioning of
      the cell membrane. Changes in erythrocyte morphology caused by the toxin are
      presented, and the early stages of interaction between toxin and membrane are
      characterised using thermal shape fluctuation analysis of red cells which
      revealed two distinct regimes of membrane-toxin interaction. 

PMID- 26303813
TI  - Life adversities and suicidal behavior in young individuals: a systematic review.
AB  - Suicidal behavior in young people is a significant public health problem.
      However, it is not yet clear whether adversities (adverse life events) may be
      related to suicidality in adolescence and early adulthood. This paper aimed to
      investigate systematically the association between the type/number of adverse
      life events and experiences and suicidal behavior in young people. We developed a
      detailed strategy to search relevant articles in Pubmed, Scopus, PsycInfo, and
      Science Direct (January 1980-January 2015) about adverse life events and suicidal
      behavior. Adverse life events and experiences included maltreatment and violence,
      loss events, intra-familial problems, school and interpersonal problems. Studies
      were restricted to suicidal behavior in young people aged 10-25 years. The search
      yielded 245 articles, of which 28 met our inclusion criteria. Most studies
      reported a strong association between adversities and suicidality (both suicidal
      ideation and attempts). Based on the main results, the number of adversities or
      negative life events experienced seemed to have a positive dose-response
      relationship with youth suicidal behavior. However, the type of event experienced
      also appeared to matter: one of the most consistent findings was the association
      between suicidal behavior and experience of sexual abuse. More prospective
      studies are needed to elucidate the relative importance of risk accumulation and
      risk specificity for youth suicide.

PMID- 26303815
TI  - On the primer binding site mutation that appears and disappears during HIV and
      SIV replication.
AB  - A recent study by Fennessey et al. (Retrovirology 12:49, 2015) described the
      optimization of a popular SIV clone by removal of four suboptimal point
      mutations. One of these mutations is present in a non-coding part of the viral
      genome and is probed in that study in more detail because of some fascinating
      properties. This primer binding site (PBS) mutation reverts rapidly to the wild
      type sequence, which the authors interpret as indicating that this mutation
      exerts a profound fitness impact. The authors proposed the involvement of a
      cellular DNA repair mechanism in the reversion. Furthermore, it was suggested
      that premature termination of reverse transcription can explain why some of the
      viral progeny still contained the mutant sequence. However, we argue that all
      these special properties are a direct consequence of the unique nature of the
      viral PBS motif. The PBS binds the tRNA primer for reverse transcription and the
      viral progeny inherits either the sequence of the cellular tRNA or the PBS
      sequence of the viral RNA genome. The presence of a variant tRNA species explains
      the rapid appearance and disappearance of a variant PBS sequence. 

PMID- 26303816
TI  - The effects of (-)-epicatechin on endothelial cells involve the G protein-coupled
      estrogen receptor (GPER).
AB  - We have provided evidence that the stimulatory effects of (-)-epicatechin ((-)
      EPI) on endothelial cell nitric oxide (NO) production may involve the
      participation of a cell-surface receptor. Thus far, such entity(ies) has not been
      fully elucidated. The G protein-coupled estrogen receptor (GPER) is a cell
      surface receptor that has been linked to protective effects on the cardiovascular
      system and activation of intracellular signaling pathways (including NO
      production) similar to those reported with (-)-EPI. In bovine coronary artery
      endothelial cells (BCAEC) by the use of confocal imaging, we evidence the
      presence of GPER at the cell-surface and on F-actin filaments. Using in silico
      studies we document the favorable binding mode between (-)-EPI and GPER. Such
      binding is comparable to that of the GPER agonist, G1. By the use of selective
      blockers, we demonstrate that the activation of ERK 1/2 and CaMKII by (-)-EPI is
      dependent on the GPER/c-SRC/EGFR axis mimicking those effects noted with G1. We
      also evidence by the use of siRNA the role that GPER has on mediating ERK1/2
      activation by (-)-EPI. GPER appears to be coupled to a non Galphai/o or Galphas,
      protein subtype. To extrapolate our findings to an ex vivo model, we employed
      phenylephrine pre-contracted aortic rings evidencing that (-)-EPI can mediate
      vasodilation through GPER activation. In conclusion, we provide evidence that
      suggests the GPER as a potential mediator of (-)-EPI effects and highlights the
      important role that GPER may have on cardiovascular system protection. 

PMID- 26303818
TI  - Remote ischaemic preconditioning versus sham procedure for abdominal aortic
      aneurysm repair: an external feasibility randomized controlled trial.
AB  - BACKGROUND: Despite advances in perioperative care, elective abdominal aorta
      aneurysm (AAA) repair carries significant morbidity and mortality. Remote
      ischaemic preconditioning (RIC) is a physiological phenomenon whereby a brief
      episode of ischaemia-reperfusion protects against a subsequent longer ischaemic
      insult. Trials in cardiovascular surgery have shown that RIC can protect
      patients' organs during surgery. The aim of this study was to investigate whether
      RIC could be successfully introduced in elective AAA repair and to obtain the
      information needed to design a multi-centre RCT. METHODS: Consecutive patients
      presenting for elective AAA repair, using an endovascular (EVAR) or open
      procedure, in a single large city hospital in the UK were assessed for trial
      eligibility. Patients who consented to participate were randomized to receive RIC
      (three cycles of 5 min ischaemia followed by 5 min reperfusion in the upper arm
      immediately before surgery) or a sham procedure. Patients were followed up for 6
      months. We assessed eligibility and consent rates, the logistics of RIC
      implementation, randomization, blinding, data capture, patient and staff opinion,
      and variability and frequency of clinical outcome measures. RESULTS: Between
      January 2010 and December 2012, 98 patients were referred for AAA repair, 93 were
      screened, 85 (91%) were eligible, 70 were approached for participation and 69
      consented to participate; 34 were randomized to RIC and 35 to the sham procedure.
      There was a greater than expected variation in the complexity of EVAR that
      impacted the outcomes. Acute kidney injury occurred in 28 (AKIN 1: 23%; AKIN 2:
      15% and AKIN 3: 3%) and 7 (10%) had a perioperative myocardial infarction.
      Blinding was successful, and interviews with participants and staff indicated
      that the procedure was acceptable. There were no adverse events secondary to the
      intervention in the 6 months following the intervention. CONCLUSIONS: This study
      provided essential information for the planning and design of a multi-centre RCT
      to assess effectiveness of RIC for improving clinical outcomes in elective AAA
      repair. Patient consent was high, and the RIC intervention was carried out with
      minimal disruption to clinical care. The allocation scheme for a definite trial
      should take into account both the surgical procedure and its complexity to avoid
      confounding the effect of the RIC, as was observed in this study. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN19332276 (date of registration: 16
      March 2012). The trial protocol is available from the corresponding author.

PMID- 26303819
TI  - Difference of microbial community stressed in artificial pit muds for Luzhou
      flavour liquor brewing revealed by multiphase culture-independent technology.
AB  - AIMS: Artificial pit muds (APMs) is produced by peats, aged pit muds, yellow and
      black clays etc. and is one of essential factors for Luzhou-flavour liquor
      production. The microbial community of APMs significantly influence the quality
      of Luzhou-flavour liquor. The aim of this study was to investigate the
      differences in bacterial, archaeal and fungal community of APMs, starters and
      materials. METHODS AND RESULTS: Multiphase culture-independent technology were
      employed in this study, including nested PCR-denaturing gradient gel
      electrophoresis (nested PCR-DGGE), phospholipid fatty acid (PLFA), phospholipid
      ether lipids (PLEL) and fluorescence in situ hybridization (FISH) analysis.
      Results suggested that the microbial diversity significantly changed under
      environmental stress and different culture patterns during APMs cultivation. The
      dominant bacteria in APMs mainly fell into Clostridiales, Lactobacillales,
      Bacteroidales and Rhizobiales, Archaea affiliated with Methanomicrobiales and
      Methanosarcinales, and fungi belonged to Saccharomycetales and Eurotiales.
      Furthermore, the microbial community structures of APMs cultured by ground pile
      pattern were more similar with that of aged pit muds, meanwhile, the relative
      bands intensities of microbes, which are the main contributors for liquor
      brewing, increased with the culture times. CONCLUSIONS: Not only the niche
      selection and biogeochemical properties of APMs, but also the mutual
      collaboration and constraint between different microbes may result in enriching
      different liquor-brewing microbes into APMs. SIGNIFICANCE AND IMPACT OF THE
      STUDY: APM cultivation technology was necessary to promote enriching functional
      liquor-brewing microbes into APMs. These results may facilitate understanding the
      microbial succession during APMs manufacture.

PMID- 26303820
TI  - Prolonged ischemia elicits acute allograft rejection involved in CXCR3 activation
      in rat kidney transplants.
AB  - BACKGROUND: Acute rejection is a major obstacle in patients with prolonged
      ischemia in deceased-donor renal transplantation. Chemokines and their receptors
      play a critical role in leukocyte trafficking, resulting in allograft rejection;
      therefore, the role of chemokine receptor CXCR3 in acute rejection induced by
      prolonged ischemia in rat kidney transplantation models was evaluated. METHODS:
      Syngeneic and allogeneic renal transplantations were performed. For cold
      ischemia, grafts were stored in 4.0 degrees C University of Wisconsin solution
      for 12 or 16 h. Serum and renal tissues were harvested 7.0 d after surgery and
      serum TNF-alpha, IL-6, and renal function were measured. Graft histology was
      stained with periodic acid-Schiff and immunohistochemical staining and further
      evaluated for signs of acute rejection. CXCR3 proteins were quantified by Western
      blot. The transplanted rats were divided into 4 groups as follows: iso-12-h =
      isogeneic transplant with 12-h CIT graft; iso-16-h = isogeneic kidney transplant
      with 16-h CIT graft; allo-12-h = allogeneic renal transplant with 12-h CIT graft;
      allo-16 h = allogeneic renal transplant with 16-h CIT graft; and 16 h+T =
      allogeneic 16-h CIT graft received tacrolimus. RESULTS: Prolonged cold ischemia
      time (CIT; 16 h) enhanced acute glomerular damage, interstitial inflammation, and
      tubulointerstitial cellular infiltration in allografts with and without
      immunosuppressant tacrolimus; but it was not apparent in the isografts. The
      expression of CXCR3 protein and the proportion of CXCR3-positive cells were
      significantly higher in the allo-16 h and 16 h +T groups than that in the allo-12
      h group 7d post-surgery. CONCLUSIONS: CIT triggered acute rejection in
      allogeneic, but not in isogeneic, kidney transplants, accompanied by an elevation
      of leukocyte recruitment and damaged graft function. The upregulated expression
      of chemokine receptor CXCR3 promoted inflammatory infiltration and acute
      allograft rejection.

PMID- 26303821
TI  - Use of short-term breath measures to estimate daily methane production by cattle.
AB  - Methods to measure enteric methane (CH4) emissions from individual ruminants in
      their production environment are required to validate emission inventories and
      verify mitigation claims. Estimates of daily methane production (DMP) based on
      consolidated short-term emission measurements are developing, but method
      verification is required. Two cattle experiments were undertaken to test the
      hypothesis that DMP estimated by averaging multiple short-term breath measures of
      methane emission rate did not differ from DMP measured in respiration chambers
      (RC). Short-term emission rates were obtained from a GreenFeed Emissions
      Monitoring (GEM) unit, which measured emission rate while cattle consumed a
      dispensed supplement. In experiment 1 (Expt. 1), four non-lactating cattle
      (LW=518 kg) were adapted for 18 days then measured for six consecutive periods.
      Each period consisted of 2 days of ad libitum intake and GEM emission measurement
      followed by 1 day in the RC. A prototype GEM unit releasing water as an
      attractant (GEM water) was also evaluated in Expt. 1. Experiment 2 (Expt. 2) was
      a larger study based on similar design with 10 cattle (LW=365 kg), adapted for 21
      days and GEM measurement was extended to 3 days in each of the six periods. In
      Expt. 1, there was no difference in DMP estimated by the GEM unit relative to the
      RC (209.7 v. 215.1 g CH(4)/day) and no difference between these methods in
      methane yield (MY, 22.7 v. 23.7 g CH(4)/kg of dry matter intake, DMI). In Expt.
      2, the correlation between GEM and RC measures of DMP and MY were assessed using
      95% confidence intervals, with no difference in DMP or MY between methods and
      high correlations between GEM and RC measures for DMP (r=0.85; 215 v. 198 g
      CH(4)/day SEM=3.0) and for MY (r=0.60; 23.8 v. 22.1 g CH(4)/kg DMI SEM=0.42).
      When data from both experiments was combined neither DMP nor MY differed between
      GEM- and RC-based measures (P>0.05). GEM water-based estimates of DMP and MY were
      lower than RC and GEM (P<0.05). Cattle accessed the GEM water unit with similar
      frequency to the GEM unit (2.8 v. 3.5 times/day, respectively) but eructation
      frequency was reduced from 1.31 times/min (GEM) to once every 2.6 min (GEM
      water). These studies confirm the hypothesis that DMP estimated by averaging
      multiple short-term breath measures of methane emission rate using GEM does not
      differ from measures of DMP obtained from RCs. Further, combining many short-term
      measures of methane production rate during supplement consumption provides an
      estimate of DMP, which can be usefully applied in estimating MY.

PMID- 26303822
TI  - Effectiveness of guideline dissemination and implementation strategies on health
      care professionals' behaviour and patient outcomes in the cancer care context: a
      systematic review protocol.
AB  - BACKGROUND: Health care professionals (HCPs) are able to make effective decisions
      regarding patient care through the use of systematically developed clinical
      practice guidelines (CPGs). These recommendations are especially important in a
      cancer health care context as patients are exposed to a multitude of
      interdisciplinary HCPs offering high-quality care throughout diagnosis,
      treatment, survivorship and palliative care. Although a large number of CPGs
      targeted towards cancer are widely disseminated, it is unknown whether
      implementation strategies targeting the use of these guidelines are effective in
      effecting HCP behaviour and patient outcomes in the cancer care context. The
      purpose of this systematic review will be to determine the effectiveness of
      different CPG dissemination and implementation interventions on HCPs' behaviour
      and patient outcomes in the cancer health care context. METHODS/DESIGN: Five
      electronic databases (CINAHL, the Cochrane Controlled Trials Register, MEDLINE
      via Ovid, EMBASE via Ovid and PsycINFO via Ovid) will be searched to include all
      studies examining the dissemination and/or implementation of CPGs in a cancer
      care setting targeting all HCPs. CPG implementation strategies will be included
      if the CPGs were systematically developed (e.g. literature review/evidence
      informed, expert panel, evidence appraisal). The studies will be limited to
      randomized controlled trials, controlled clinical trials and quasi-experimental
      (interrupted time series, controlled before-and-after designs) studies. Two
      independent reviewers will assess articles for eligibility, data extraction and
      quality appraisal. DISCUSSION: The aim of this review is to inform cancer care
      health care professionals and policymakers about evidence-based implementation
      strategies that will allow for effective use of CPGs. SYSTEMATIC REVIEW
      REGISTRATION: PROSPERO CRD42015019331.

PMID- 26303823
TI  - Predicting Mortality after Severe Acute Kidney Injury: A Step Forward but Not
      Close to the Finish Line.

PMID- 26303824
TI  - Do native predators benefit from non-native prey?
AB  - Despite knowledge on invasive species' predatory effects, we know little of their
      influence as prey. Non-native prey should have a neutral to positive effect on
      native predators by supplementing the prey base. However, if non-native prey
      displace native prey, then an invader's net influence should depend on both its
      abundance and value relative to native prey. We conducted a meta-analysis to
      quantify the effect of non-native prey on native predator populations. Relative
      to native prey, non-native prey similarly or negatively affect native predators,
      but only when studies employed a substitutive design that examined the effects of
      each prey species in isolation from other prey. When native predators had access
      to non-native and native prey simultaneously, predator abundance increased
      significantly relative to pre-invasion abundance. Although non-native prey may
      have a lower per capita value than native prey, they seem to benefit native
      predators by serving as a supplemental prey resource.

PMID- 26303825
TI  - Lymph node evaluation for treatment of adenocarcinoma of the pancreas.
AB  - BACKGROUND: Increased lymph node evaluation has been associated with improved
      survival rates in patients with pancreatic cancer. We sought to evaluate the
      trends and factors associated with lymph node examination over time and the
      effects on survival. METHODS: Using the Surveillance, Epidemiology and End
      Results database, we conducted an analysis of adults with adenocarcinoma of the
      pancreas who underwent surgical resection. Using the Cochrane Armitage test for
      trend and logistic regression we identified factors associated with lymph node
      evaluation. Kaplan-Meier and Cox proportional hazards modeling were used to
      examine survival. RESULTS: We identified 4831 patients who underwent surgical
      resection from 1990 to 2010. The proportion of patients with 15 or more lymph
      nodes evaluated increased from 16% to 42% (p < 0.05) and the median number of
      lymph nodes examined increased from 7 to 15 nodes (p < 0.05) during the study
      period. Overall, 56% of patients had lymph node metastases; this proportion
      significantly increased during the study period. Factors that were independently
      associated with less than 15 lymph nodes evaluated included male gender, receipt
      of pre-operative radiation therapy, early year of diagnosis, older age, and
      missing information on tumor grade and size (p < 0.05). Survival rates
      significantly improved when 15 or more lymph nodes were examined. CONCLUSION: We
      observed a significant increase in the number of lymph nodes evaluated with
      pancreas cancer resection over time. Lymph node evaluation was significantly
      associated with patient, tumor, and treatment characteristics. Our results
      suggest that adequate lymph node evaluation is associated with improved survival.

PMID- 26303826
TI  - IN-VITRO evidence for the protective properties of the main components of the
      Mediterranean diet against colorectal cancer: A systematic review.
AB  - AIM: Epidemiological studies have shown that the incidence and mortality rates of
      colorectal cancer (CRC) vary over 10-fold worldwide where within Westernized
      societies lower rates are observed amongst populations living within the
      Mediterranean basin, suggesting a significant influence of environment and
      dietary style in CRC carcinogenesis. Interpretation of the data concerning the
      benefits of mediterranean (MD) diet is difficult in vivo because of the
      variability of alimentary regimens used, the differing compliance with dietary
      supplementation and because of the non-uniform duration of patient cohort
      observation. Therefore, the aim of this review is to evaluate the in-vitro
      effects on colorectal cancer cell lines. METHODS: the literature concerning the
      in-vitro effects of 4 of the principal components symbolizing the MD such as
      olive oil (polyphenol), red chili (capsaicin), tomato (lycopene) and red grapes
      (resveratrol) have been systematically reviewed. RESULTS: Several studies have
      demonstrated that polyphenols form olive oil, lycopene, resveratrol and capsaicin
      have multiple anticancer properties affecting several metabolic pathways involved
      in cancerogenesis, apoptosis, and metastasis in CRC cell lines. CONCLUSION: This
      review summarizes some of the most recent data potentially supportive of the use
      of MD in CRC chemoprevention, analyzing the in vitro effects of individual
      components of the MD on CRC cell development, progression, metastasis and
      apoptosis.

PMID- 26303827
TI  - Exposure to violence in childhood is associated with higher body mass index in
      adolescence.
AB  - To determine whether different types of childhood adversity are associated with
      body mass index (BMI) in adolescence, we studied 147 adolescents aged 13-17
      years, 41% of whom reported exposure to at least one adversity (maltreatment,
      abuse, peer victimization, or witness to community or domestic violence). We
      examined associations between adversity type and age- and sex-specific BMI z
      scores using linear regression and overweight and obese status using logistic
      regression. We adjusted for potential socio-demographic, behavioral, and
      psychological confounders and tested for effect modification by gender.
      Adolescents with a history of sexual abuse, emotional abuse, or peer
      victimization did not have significantly different BMI z-scores than those
      without exposure (p>0.05 for all comparisons). BMI z-scores were higher in
      adolescents who had experienced physical abuse (beta=0.50, 95% CI 0.12-0.91) or
      witnessed domestic violence (beta=0.85, 95% CI 0.30-1.40). Participants who
      witnessed domestic violence had almost 6 times the odds of being overweight or
      obese (95% CI: 1.09-30.7), even after adjustment for potential confounders. No
      gender-by-adversity interactions were found. Exposure to violence in childhood is
      associated with higher adolescent BMI. This finding highlights the importance of
      screening for violence in pediatric practice and providing obesity prevention
      counseling for youth.

PMID- 26303828
TI  - Activity of T-DM1 in Her2-positive breast cancer brain metastases.
AB  - Brain metastases (BM) are frequently diagnosed in metastatic Her2-positive breast
      cancer. Local treatment remains the standard of care but lapatinib plus
      capecitabine was recently established as systemic therapy option. Due to a
      disruption of the blood-brain/tumour-barrier at metastatic sites, even large
      molecules may penetrate into the central nervous system (CNS). Here, we report on
      the activity of T-DM1 in Her2-positive breast cancer BM. T-DM1 was administered
      at a dose of 3.6 mg once every 3 weeks as primary systemic therapy for BM or upon
      documented CNS progression after initial local treatment. Thus, this study
      allowed for the appraisal of T-DM1 activity in BM. Restaging was conducted every
      12 weeks with MRI or whenever symptoms of disease progression occurred. Ten
      patients were included; in two asymptomatic subjects, T-DM1 was administered as
      primary therapy, while eight had progressive BM. All patients had received prior
      treatment with trastuzumab, six had already received lapatinib, and three
      pertuzumab as well. Three patients had partial remission of BM, and two patient
      had stable disease lasting for >=6 months; two further patients had stable
      disease for <6 months while three progressed despite treatment. At 8.5 months
      median follow-up, intracranial PFS was 5 months, and median OS from initiation of
      T-DM1 was not reached. Local treatment of BM remains the standard of care;
      lapatinib plus capecitabine is currently the best established systemic therapy
      option. Still, T-DM1 apparently offers relevant clinical activity in BM and
      further investigation is warranted.

PMID- 26303829
TI  - Minimal Peptidoglycan (PG) Turnover in Wild-Type and PG Hydrolase and Cell
      Division Mutants of Streptococcus pneumoniae D39 Growing Planktonically and in
      Host-Relevant Biofilms.
AB  - We determined whether there is turnover of the peptidoglycan (PG) cell wall of
      the ovococcus bacterial pathogen Streptococcus pneumoniae (pneumococcus). Pulse
      chase experiments on serotype 2 strain D39 radiolabeled with N-acetylglucosamine
      revealed little turnover and release of PG breakdown products during growth
      compared to published reports of PG turnover in Bacillus subtilis. PG dynamics
      were visualized directly by long-pulse-chase-new-labeling experiments using two
      colors of fluorescent d-amino acid (FDAA) probes to microscopically detect
      regions of new PG synthesis. Consistent with minimal PG turnover, hemispherical
      regions of stable "old" PG persisted in D39 and TIGR4 (serotype 4) cells grown in
      rich brain heart infusion broth, in D39 cells grown in chemically defined medium
      containing glucose or galactose as the carbon source, and in D39 cells grown as
      biofilms on a layer of fixed human epithelial cells. In contrast, B. subtilis
      exhibited rapid sidewall PG turnover in similar FDAA-labeling experiments. High
      performance liquid chromatography (HPLC) analysis of biochemically released
      peptides from S. pneumoniae PG validated that FDAAs incorporated at low levels
      into pentamer PG peptides and did not change the overall composition of PG
      peptides. PG dynamics were also visualized in mutants lacking PG hydrolases that
      mediate PG remodeling, cell separation, or autolysis and in cells lacking the
      MapZ and DivIVA division regulators. In all cases, hemispheres of stable old PG
      were maintained. In PG hydrolase mutants exhibiting aberrant division plane
      placement, FDAA labeling revealed patches of inert PG at turns and bulge points.
      We conclude that growing S. pneumoniae cells exhibit minimal PG turnover compared
      to the PG turnover in rod-shaped cells. IMPORTANCE: PG cell walls are unique to
      eubacteria, and many bacterial species turn over and recycle their PG during
      growth, stress, colonization, and virulence. Consequently, PG breakdown products
      serve as signals for bacteria to induce antibiotic resistance and as activators
      of innate immune responses. S. pneumoniae is a commensal bacterium that colonizes
      the human nasopharynx and opportunistically causes serious respiratory and
      invasive diseases. The results presented here demonstrate a distinct demarcation
      between regions of old PG and regions of new PG synthesis and minimal turnover of
      PG in S. pneumoniae cells growing in culture or in host-relevant biofilms. These
      findings suggest that S. pneumoniae minimizes the release of PG breakdown
      products by turnover, which may contribute to evasion of the innate immune
      system.

PMID- 26303830
TI  - Genome-Based Comparison of Cyclic Di-GMP Signaling in Pathogenic and Commensal
      Escherichia coli Strains.
AB  - The ubiquitous bacterial second messenger cyclic di-GMP (c-di-GMP) has recently
      become prominent as a trigger for biofilm formation in many bacteria. It is
      generated by diguanylate cyclases (DGCs; with GGDEF domains) and degraded by
      specific phosphodiesterases (PDEs; containing either EAL or HD-GYP domains). Most
      bacterial species contain multiples of these proteins with some having specific
      functions that are based on direct molecular interactions in addition to their
      enzymatic activities. Escherichia coli K-12 laboratory strains feature 29 genes
      encoding GGDEF and/or EAL domains, resulting in a set of 12 DGCs, 13 PDEs, and
      four enzymatically inactive "degenerate" proteins that act by direct
      macromolecular interactions. We present here a comparative analysis of GGDEF/EAL
      domain-encoding genes in 61 genomes of pathogenic, commensal, and probiotic E.
      coli strains (including enteric pathogens such as enteroaggregative,
      enterohemorrhagic, enteropathogenic, enterotoxigenic, and adherent and invasive
      Escherichia coli and the 2011 German outbreak O104:H4 strain, as well as
      extraintestinal pathogenic E. coli, such as uropathogenic and meningitis
      associated E. coli). We describe additional genes for two membrane-associated
      DGCs (DgcX and DgcY) and four PDEs (the membrane-associated PdeT, as well as the
      EAL domain-only proteins PdeW, PdeX, and PdeY), thus showing the pangenome of E.
      coli to contain at least 35 GGDEF/EAL domain proteins. A core set of only eight
      proteins is absolutely conserved in all 61 strains: DgcC (YaiC), DgcI (YliF),
      PdeB (YlaB), PdeH (YhjH), PdeK (YhjK), PdeN (Rtn), and the degenerate proteins
      CsrD and CdgI (YeaI). In all other GGDEF/EAL domain genes, diverse point and
      frameshift mutations, as well as small or large deletions, were discovered in
      various strains. IMPORTANCE: Our analysis reveals interesting trends in
      pathogenic Escherichia coli that could reflect different host cell adherence
      mechanisms. These may either benefit from or be counteracted by the c-di-GMP
      stimulated production of amyloid curli fibers and cellulose. Thus, EAEC, which
      adhere in a "stacked brick" biofilm mode, have a potential for high c-di-GMP
      accumulation due to DgcX, a strongly expressed additional DGC. In contrast, EHEC
      and UPEC, which use alternative adherence mechanisms, tend to have extra PDEs,
      suggesting that low cellular c-di-GMP levels are crucial for these strains under
      specific conditions. Overall, our study also indicates that GGDEF/EAL domain
      proteins evolve rapidly and thereby contribute to adaptation to host-specific and
      environmental niches of various types of E. coli.

PMID- 26303831
TI  - Vibrio cholerae leuO Transcription Is Positively Regulated by ToxR and
      Contributes to Bile Resistance.
AB  - Vibrio cholerae is an aquatic organism and facultative human pathogen that
      colonizes the small intestine. In the small intestine, V. cholerae is exposed to
      a variety of antimicrobial compounds, including bile. V. cholerae resistance to
      bile is multifactorial and includes alterations in the membrane permeability
      barrier that are mediated by ToxR, a membrane-associated transcription factor.
      ToxR has also been shown to be required for activation of the LysR family
      transcription factor leuO in response to cyclic dipeptides. LeuO has been
      implicated in the regulation of multiple V. cholerae phenotypes, including
      biofilm production and virulence. In this study, we investigated the effects of
      bile on leuO expression. We show that leuO transcription increased in response to
      bile and bile salts but not in response to other detergents. The bile-dependent
      increase in leuO expression was dependent on ToxR, which was found to bind
      directly to the leuO promoter. The periplasmic domain of ToxR was required for
      basal leuO expression and for the bile-dependent induction of both leuO and ompU
      transcription. V. cholerae mutants that did not express leuO exhibited increased
      bile susceptibility, suggesting that LeuO contributes to bile resistance. Our
      collective results demonstrate that ToxR activates leuO expression in response to
      bile and that LeuO is a component of the ToxR-dependent responses that contribute
      to bile resistance. IMPORTANCE: The success of Vibrio cholerae as a human
      pathogen is dependent upon its ability to rapidly adapt to changes in its growth
      environment. Growth in the human gastrointestinal tract requires the expression
      of genes that provide resistance to host antimicrobial compounds, including bile.
      In this work, we show for the first time that the LysR family regulator LeuO
      mediates responses in V. cholerae that contribute to bile resistance.

PMID- 26303833
TI  - Biomarkers in Alzheimer's disease: understanding disease trajectory and
      therapeutic targets.

PMID- 26303832
TI  - In Vivo Formation of the Protein Disulfide Bond That Enhances the Thermostability
      of Diphosphomevalonate Decarboxylase, an Intracellular Enzyme from the
      Hyperthermophilic Archaeon Sulfolobus solfataricus.
AB  - In the present study, the crystal structure of recombinant diphosphomevalonate
      decarboxylase from the hyperthermophilic archaeon Sulfolobus solfataricus was
      solved as the first example of an archaeal and thermophile-derived
      diphosphomevalonate decarboxylase. The enzyme forms a homodimer, as expected for
      most eukaryotic and bacterial orthologs. Interestingly, the subunits of the
      homodimer are connected via an intersubunit disulfide bond, which presumably
      formed during the purification process of the recombinant enzyme expressed in
      Escherichia coli. When mutagenesis replaced the disulfide-forming cysteine
      residue with serine, however, the thermostability of the enzyme was significantly
      lowered. In the presence of beta-mercaptoethanol at a concentration where the
      disulfide bond was completely reduced, the wild-type enzyme was less stable to
      heat. Moreover, Western blot analysis combined with nonreducing SDS-PAGE of the
      whole cells of S. solfataricus proved that the disulfide bond was predominantly
      formed in the cells. These results suggest that the disulfide bond is required
      for the cytosolic enzyme to acquire further thermostability and to exert activity
      at the growth temperature of S. solfataricus. IMPORTANCE: This study is the first
      report to describe the crystal structures of archaeal diphosphomevalonate
      decarboxylase, an enzyme involved in the classical mevalonate pathway. A
      stability-conferring intersubunit disulfide bond is a remarkable feature that is
      not found in eukaryotic and bacterial orthologs. The evidence that the disulfide
      bond also is formed in S. solfataricus cells suggests its physiological
      importance.

PMID- 26303834
TI  - Effect of 24-h continuous rotigotine treatment on stationary and non-stationary
      locomotion in de novo patients with Parkinson disease in an open-label
      uncontrolled study.
AB  - The aim of this study was to investigate the effect of a rotigotine transdermal
      patch on stationary and non-stationary locomotion in de novo Parkinson disease
      (PD) patients in an open-label uncontrolled study. A 3-D gait analysis system was
      used to investigate four different locomotor tasks: steady-state linear walking,
      gait initiation, gait termination and 180 degrees -turning. A series of gait
      variables were measured for each locomotor task. PD patients who received
      rotigotine treatment (4-8 mg) displayed: (1) increased step length, gait speed,
      cadence and arm oscillations, and reduced double support duration and step
      asymmetry during steady-state linear gait; (2) increased initial step length
      during gait initiation; (3) increased final step length and gait speed, and
      decreased stability index during gait termination; (4) decreased duration of
      turning and head-pelvis delays during 180 degrees -turning. The main finding that
      emerges from the present study is that the dopamine agonist rotigotine can
      improve various aspects of gait in de novo PD patients.

PMID- 26303835
TI  - e-Health: a position statement of the European Society of Cardiology.

PMID- 26303837
TI  - Nursing in Korea: how to awaken the sleeping giant.

PMID- 26303838
TI  - Nursing and universal health coverage.

PMID- 26303839
TI  - Nursing diplomacy and influence.

PMID- 26303841
TI  - Primer removal during mammalian mitochondrial DNA replication.
AB  - The small circular mitochondrial genome in mammalian cells is replicated by a
      dedicated replisome, defects in which can cause mitochondrial disease in humans.
      A fundamental step in mitochondrial DNA (mtDNA) replication and maintenance is
      the removal of the RNA primers needed for replication initiation. The nucleases
      RNase H1, FEN1, DNA2, and MGME1 have been implicated in this process. Here we
      review the role of these nucleases in the light of primer removal pathways in
      mitochondria, highlight associations with disease, as well as consider the
      implications for mtDNA replication initiation. 

PMID- 26303836
TI  - The Role of Activated Microglia and Resident Macrophages in the Neurovascular
      Unit during Cerebral Ischemia: Is the Jury Still Out?
AB  - Paracrine signaling in the neurovascular unit (NVU) is aimed to adjust the supply
      of oxygen and nutrients to metabolic demands of the brain in a feed-forward
      manner. Cerebral ischemia (CI) severely disrupts this homeostatic mechanism and
      also causes activation of microglia and resident macrophages in the brain.
      Contradictory data exist on the time pattern of microglial activation and
      polarization during CI, on molecular mechanisms that trigger them and on effects
      of microglia-derived cytokines on brain cells. It appears that conditions that
      occur during transient ischemia or in the penumbra of focal ischemia in vivo or
      equivalent conditions in vitro trigger polarization of resting
      microglia/macrophages into the M2 phenotype, which mainly exerts anti
      inflammatory and protective effects in the brain, while prolonged ischemia with
      abundant necrosis promotes microglial polarization into the M1 phenotype. During
      the later stages of recovery, microglia that polarized initially into the M2
      phenotype can shift into the M1 phenotype. Thus, it appears that cells with both
      phenotypes are present in the affected area, but their relative amount changes in
      time and probably depends on the proximity to the ischemic core. It was assumed
      that cells with the M1 phenotype exert detrimental effects on neurons and
      contribute to the blood-brain barrier opening. Several M1 phenotype-specific
      cytokines exert protective effects on astrocytes, which could be important for
      reactive gliosis occurring after ischemia. Thus, whether or not suppression of
      microglial activity after CI is beneficial for neurological outcome still remains
      unclear and current evidence suggests that no simple answer could be given to
      this question. 

PMID- 26303842
TI  - A study of pathway of care in children and adolescents with attention deficit
      hyperactivity disorder.
AB  - OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is associated with
      impairment in all aspects of the patient's life. Despite availability of
      effective treatments for ADHD, a majority of the patient lack access to or have a
      significant delay in seeking help. This study aimed to assess the pathway of care
      in ADHD among patients attending the outpatient psychiatric services of a
      tertiary care centre in India. METHODS: 57 newly registered cases of the age
      group 6-16 years with the diagnosis of ADHD as per DSM-IV-TR criteria were
      included in the study. Pathway of care was assessed on the semi structured
      proforma. RESULTS: The mean duration of delay in seeking help for ADHD symptoms
      was 3.96 Years (SD=1.96). Only 50% of the subjects consulted psychiatrists as
      first contact. Majority of the patients (45.61%) were referred by school
      teachers. Major reason given by the family members was that the patient was
      naughty rather than having any disorder for not seeking treatment in (89.47%).
      CONCLUSION: Our study showed that there was lack of recognition of ADHD at the
      level of other qualified practitioners and subsequent delay in referral to CAMHS.
      Sociocultural beliefs affected the help seeking by the parents.

PMID- 26303843
TI  - On the practice of ignoring center-patient interactions in evaluating hospital
      performance.
AB  - We evaluate the performance of medical centers based on a continuous or binary
      patient outcome (e.g., 30-day mortality). Common practice adjusts for differences
      in patient mix through outcome regression models, which include patient-specific
      baseline covariates (e.g., age and disease stage) besides center effects. Because
      a large number of centers may need to be evaluated, the typical model postulates
      that the effect of a center on outcome is constant over patient characteristics.
      This may be violated, for example, when some centers are specialized in children
      or geriatric patients. Including interactions between certain patient
      characteristics and the many fixed center effects in the model increases the risk
      for overfitting, however, and could imply a loss of power for detecting centers
      with deviating mortality. Therefore, we assess how the common practice of
      ignoring such interactions impacts the bias and precision of directly and
      indirectly standardized risks. The reassuring conclusion is that the common
      practice of working with the main effects of a center has minor impact on
      hospital evaluation, unless some centers actually perform substantially better on
      a specific group of patients and there is strong confounding through the
      corresponding patient characteristic. The bias is then driven by an interplay of
      the relative center size, the overlap between covariate distributions, and the
      magnitude of the interaction effect. Interestingly, the bias on indirectly
      standardized risks is smaller than on directly standardized risks. We illustrate
      our findings by simulation and in an analysis of 30-day mortality on Riksstroke.

PMID- 26303844
TI  - Bacillus gossypii sp. nov., isolated from the stem of Gossypium hirsutum.
AB  - A Gram-stain-positive, facultatively anaerobic, endospore-forming organism,
      isolated from the stem of Gossypium hirsutum, was studied to determine its
      taxonomic position. On the basis of 16S rRNA gene sequence similarity
      comparisons, strain JM-267T was grouped in the genus Bacillus, related most
      closely to the type strains of Bacillus simplex and Bacillus huizhouensis (both
      97.8%), Bacillus muralis (97.7%), Bacillus butanolivorans and Bacillus
      psychrosaccharolyticus (both 97.3%). 16S rRNA gene sequence similarity to the
      sequences of the type strains of other Bacillus species was < 97.0%. The fatty
      acid profile supported the grouping of the strain to the genus Bacillus. As major
      fatty acids, anteiso-C15:0, iso-C15:0, iso-C14:0 and iso-C16:0 were detected. The
      polar lipid profile contained the major components diphosphatidylglycerol,
      phosphatidylglycerol and phosphatidylethanolamine. The major quinone was
      menaquinone 7 (MK-7). DNA-DNA hybridizations with B. simplex DSM 1321T, B.
      huizhouensis GSS03T, B. muralis LMG 20238T, B. butanolivorans LMG 23974T and B.
      psychrosaccharolyticus DSM 6T resulted in values clearly below 70%. In addition,
      physiological and biochemical test results allowed the clear phenotypic
      differentiation of strain JM-267T from the most closely related species. Hence,
      strain JM-267T is considered to represent a novel species of the genus Bacillus,
      for which the name Bacillus gossypii sp. nov. is proposed. The type strain is JM
      267T ( = DSM 100034T = LMG 28742T).

PMID- 26303845
TI  - Adsorption of guanidinium collectors on aluminosilicate minerals - a density
      functional study.
AB  - In this density functional theory based investigation, we have modelled and
      studied the adsorption behaviour of guanidinium cations and substituted (phenyl,
      methoxy phenyl, nitro phenyl and di-nitro phenyl) guanidinium cationic collectors
      on the basal surfaces of kaolinite and goethite. The adsorption behaviour is
      assessed in three different media, such as gas, explicit water and pH medium, to
      understand the affinity of GC collectors to the SiO4 tetrahedral and AlO6
      octahedral surfaces of kaolinite. The tetrahedral siloxane surface possesses a
      larger binding affinity to GC collectors than the octahedral sites due to the
      presence of surface exposed oxygen atoms that are active in the intermolecular
      interactions. Furthermore, the inductive electronic effects of substituted
      guanidinium cations also play a key role in the adsorption mechanism. Highly
      positive cations result in a stronger electrostatic interaction and preferential
      adsorption with the kaolinite surfaces than low positive cations. Computed
      interaction energies and electron densities at the bond critical points suggest
      that the adsorption of guanidinium cations on the surfaces of kaolinite and
      goethite is due to the formation of intra/inter hydrogen bonding networks. Also,
      the electrostatic interaction favours the high adsorption ability of GC
      collectors in the pH medium than gas phase and water medium. The structures and
      energies of GC collectors pave an intuitive view for future experimental studies
      on mineral flotation. 

PMID- 26303846
TI  - Phenotypic heterogeneity and temporal expression of the capsular polysaccharide
      in Staphylococcus aureus.
AB  - Bacteria respond to ever-changing environments through several adaptive
      strategies. This includes mechanisms leading to a high degree of phenotypic
      variability within a genetically homogeneous population. In Staphylococcus
      aureus, the capsular polysaccharide (CP) protects against phagocytosis, but also
      impedes adherence to endothelial cells and/or matrix proteins. We analysed the
      regulation of core biosynthesis genes (capA-P) necessary for CP synthesis using
      single-cell assays (immunofluorescence and promoter-activity). In persistent
      human carriers, we found a distinct subpopulation of nasal S. aureus to be CP
      positive. In vitro, cap expression is also heterogeneous and strongly growth
      phase dependent. We asked whether this peculiar expression pattern
      (earlyOff/lateHeterogen) is orchestrated by the quorum system Agr. We show that
      the Agr-driven effector molecule RNAIII promotes cap expression largely via
      inactivation of the repressor Rot. High NaCl, deletion of CodY or Sae also
      resulted in higher cap expression but did not change the earlyOFF/lateHeterogen
      expression pattern. Activity of the quorum system itself is largely homogenous
      and does not account for the observed heterogeneity of cap expression or the
      strictly growth phase dependent expression. Our findings are in contrast to the
      prevailing view that quorum sensing is the main driving force for virulence gene
      expression when bacterial cell densities increase.

PMID- 26303847
TI  - Refractory pyoderma gangrenosum treated with platelet-rich plasma.

PMID- 26303848
TI  - The effects of Malaysian propolis and Brazilian red propolis on connective tissue
      fibroblasts in the wound healing process.
AB  - BACKGROUND: To evaluate and compare the effects of ethanolic extracts of
      Malaysian propolis and Brazilian red propolis at different concentrations on the
      migration and proliferation of fibroblast cells. METHODS: Malaysian and Brazilian
      red propolis crude samples were extracted using ethanol. Their wound healing
      effects were tested in vitro on the normal human fibroblast cell line CRL-7522.
      Cell migration and proliferation assays were carried out using propolis
      concentrations of 1, 10, 100, 250, 500 and 1000 MUg/mL. The data were analyzed
      using one-way ANOVA and post hoc Bonferroni tests (alpha=0.05). RESULTS:
      Malaysian and Brazilian red propolis followed a concentration-dependent
      increasing and decreasing trend. Malaysian propolis showed the fastest migration
      rate at 250 MUg/mL which was statistically significant (p<0.05) and maximum
      proliferation at 500 MUg/mL with no significant difference (p>0.05) compared to
      control. Brazilian red propolis showed a slight increase in migration and
      proliferation at 10 and 100 MUg/mL, respectively with no significant difference
      (p>0.05) compared to control, while concentrations above these conferred
      inhibitory effects. CONCLUSION: Malaysian and Brazilian red propolis show
      potential to assist in wound healing, depending on their concentration.

PMID- 26303855
TI  - Parkinson disease: Laying the foundations for disease-modifying therapies in PD.
AB  - The results of a futility trial, which used the PPAR-gamma receptor agonist
      pioglitazone in an attempt to modify disease progression in Parkinson disease, do
      not support initiation of further trials. However, although this trial was well
      designed and conducted, we question whether it is time to fully shut the door on
      pioglitazone.

PMID- 26303850
TI  - Immune interventions in stroke.
AB  - Approaches for the effective management of acute stroke are sparse, and many
      measures for brain protection fail. However, our ability to modulate the immune
      system and modify the progression of multiple sclerosis is increasing. As a
      result, immune interventions are currently being explored as therapeutic
      interventions in acute stroke. In this Review, we compare the immunological
      features of acute stroke with those of multiple sclerosis, identify unique
      immunological features of stroke, and consider the evidence for immune
      interventions. In patients with acute stroke, microglial activation and cell
      death products trigger an inflammatory cascade that damages vessels and the
      parenchyma within minutes to hours of the ischaemia or haemorrhage. Immune
      interventions that restrict brain inflammation, vascular permeability and tissue
      oedema must be administered rapidly to reduce acute immune-mediated destruction
      and to avoid subsequent immunosuppression. Preliminary results suggest that the
      use of drugs that modify disease in multiple sclerosis might accomplish these
      goals in ischaemic and haemorrhagic stroke. Further elucidation of the immune
      mechanisms involved in stroke is likely to lead to successful immune
      interventions. 

PMID- 26303851
TI  - Type I interferon dysregulation and neurological disease.
AB  - Type I interferon is an essential component of the brain's innate immune defence,
      conferring protection against viral infection. Recently, dysregulation of the
      type I interferon pathway has been implicated in the pathogenesis of a spectrum
      of neuroinfectious and neuroinflammatory disorders. Underactivity of the type I
      interferon response is associated with a predisposition to herpes simplex
      encephalitis. Conversely, a group of 'interferonopathic' disorders, characterized
      by severe neuroinflammation and overactivity of type I interferon, has been
      described. Elucidation of the genetic basis of these Mendelian neuroinflammatory
      diseases has uncovered important links between nucleic acid sensors, innate
      immune activation and neuroinflammatory disease. These mechanisms have an
      important role in the pathogenesis of more common polygenic diseases that can
      affect the brain, such as lupus and cerebral small vessel disease. In this
      article, we review the spectrum of neurological disease associated with type I
      interferon dysregulation, as well as advances in our understanding of the
      molecular and cellular pathogenesis of these conditions. We highlight the
      potential utility of type I interferon as both a biomarker and a therapeutic
      target in neuroinflammatory disease. 

PMID- 26303857
TI  - The utility of elastic spacer hooks in internal mammary vessel preparation for
      diep anastomosis.

PMID- 26303858
TI  - Accumulative effect of food residues on intestinal gas production.
AB  - BACKGROUND: As mean transit time in the colon is longer than the interval between
      meals, several consecutive meal loads accumulate, and contribute to colonic
      biomass. Our aim was to determine the summation effect of fermentable food
      residues on intestinal gas production. METHODS: In eight healthy subjects, the
      volume of endogenous intestinal gas produced in the intestine over a 4-h period
      was measured by means of a wash-out technique, using an exogenous gas infusion
      into the jejunum (24 mL/min) and collection of the effluent via a rectal Foley
      catheter. The exogenous gas infused was labeled (5% SF6 ) to calculate the
      proportion of endogenous intestinal gas evacuated. In each subject, four
      experiments were performed >=1 week apart combining a 1-day high- or low
      flatulogenic diet with a test meal or fast. KEY RESULTS: Basal conditions: on the
      low-flatulogenic diet, intestinal gas production during fasting over the 4-h
      study period was 609 +/- 63 mL. Effect of diet: during fasting, intestinal gas
      production on the high-flatulogenic diet was 370 +/- 146 mL greater than on the
      low-flatulogenic diet (p = 0.040). Effect of test meal: on the low-flatulogenic
      diet, intestinal gas production after the test meal was 681 +/- 114 mL greater
      than during fasting (p = 0.001); a similar effect was observed on the high
      flatulogenic diet (599 +/- 174 mL more intestinal gas production after the test
      meal than during fasting; p = 0.021). CONCLUSIONS & INFERENCES: Our data
      demonstrate temporal summation effects of food residues on intestinal gas
      production. Hence, intestinal gas production depends on pre-existing and on
      recent colonic loads of fermentable foodstuffs.

PMID- 26303856
TI  - Maternal psychiatric disease and epigenetic evidence suggest a common biology for
      poor fetal growth.
AB  - BACKGROUND: We sought to identify and characterize predictors of poor fetal
      growth among variables extracted from perinatal medical records to gain insight
      into potential etiologic mechanisms. In this process we reevaluated a previously
      observed association between poor fetal growth and maternal psychiatric disease.
      METHODS: We evaluated 449 deliveries of >36 weeks gestation that occurred between
      9/2008 and 9/2010 at the Women and Infants Hospital in Providence Rhode Island.
      This study group was oversampled for Small-for-Gestational-Age (SGA) infants and
      excluded Large-for-Gestational-Age (LGA) infants. We assessed the associations
      between recorded clinical variables and impaired fetal growth: SGA or
      Intrauterine Growth Restriction (IUGR) diagnosis. After validating the previously
      observed association between maternal psychiatric disease and impaired fetal
      growth we addressed weaknesses in the prior studies by explicitly considering
      antidepressant use and the timing of symptoms with respect to pregnancy. We then
      evaluated DNA methylation levels at 27 candidate loci in placenta from a subset
      of these deliveries (n = 197) to examine if epigenetic variation could provide
      insight into the mechanisms that cause this co-morbidity. RESULTS: Infants of
      mothers with prenatal psychiatric disease (Depression, Anxiety, OCD/Panic) had
      increased odds of poor fetal growth (ORadjusted = 3.36, 95%CI: 1.38-8.14). This
      relationship was similar among those who were treated with antidepressants
      (ORadjusted = 3.69, 95%CI: 1.31-10.45) and among those who were not (ORadjusted =
      3.19, 95%CI: 1.30-7.83). Among those with a history of psychiatric disease but no
      active disease in pregnancy the ORadjusted was 0.45 (95%CI: 0.09-2.35). A locus
      near the transcription start site of the leptin receptor (cg21655790) had
      methylation levels that were decreased in the presence of: 1) SGA/IUGR, and 2)
      active but not resolved psychiatric disease (among mothers not on
      antidepressants). CONCLUSIONS: These results validate and further characterize
      the association between maternal psychiatric disease and poor fetal growth.
      Because the association appears to depend on active psychiatric disease, this
      suggests a transient and potentially modifiable pathophysiology. The molecular
      findings in this study suggest that altered leptin signaling may be involved in
      the biological mechanisms that link prenatal maternal psychiatric symptoms and
      poor fetal growth.

PMID- 26303859
TI  - Inconsistent diagnosis of acute malnutrition by weight-for-height and mid-upper
      arm circumference: contributors in 16 cross-sectional surveys from South Sudan,
      the Philippines, Chad, and Bangladesh.
AB  - BACKGROUND: The two anthropometric indicators of acute malnutrition in children
      under 5 years, i.e. a Mid-Upper Arm Circumference < 125 mm (MUAC125) or a Weight
      for-Height Z-score<-2 (WHZ-2), correlate poorly. We aimed at assessing the
      contribution of age, sex, stunting (Height-for-Age HAZ<-2), and low sitting
      standing height ratio Z-score (SSRZ in the 1st tertile of the study population,
      called hereafter 'longer legs') to this diagnosis discrepancy. METHODS: Data from
      16 cross-sectional nutritional surveys carried out by Action Against Hunger
      International in South Sudan, the Philippines, Chad, and Bangladesh fed
      multilevel, multivariate regression models, with either WHZ-2 or MUAC125 as the
      dependent variable and age, sex, stunting, and 'longer legs' as the independent
      ones. We also compared how the performance of MUAC125 and WHZ-2 to detect slim
      children, i.e. children with a low Weight-for-Age (WAZ<-2) but no linear growth
      retardation (HAZ>=-2), was modified by the contributors. RESULTS: Overall 23.1%
      of the 14,409 children were identified as acutely malnourished by either WHZ-2 or
      MUAC125, but only 28.5% of those (949/3,328) were identified by both indicators.
      Being stunted (+17.8%; 95 % CI: 14.8%; 22.8%), being a female (+16.5%; 95 % CI:
      13.5%; 19.5%) and being younger than 24 months (+33.6%; 95 % CI: 30.4%; 36.7%)
      were factors strongly associated with being detected as malnourished by MUAC125
      and not by WHZ-2, whereas having 'longer legs' moderately increased the diagnosis
      by WHZ-2 (+4.2%; 95 % CI: 0.7%; 7.6%). The sensitivity to detect slim children by
      MUAC125 was 31.0% (95 % CI: 26.8%; 35.2%) whereas it was 70.6% (95 % CI: 65.4%;
      75.9%) for WHZ-2. The sensitivity of MUAC125 was particularly affected by age
      (57.4% vs. 18.1% in children aged < 24 months vs. >= 24 months). Specificity was
      high for both indicators. CONCLUSIONS: MUAC125 should not be used as a stand
      alone criterion of acute malnutrition given its strong association with age, sex
      and stunting, and its low sensitivity to detect slim children. Having 'longer
      legs' moderately increases the diagnosis of acute malnutrition by WHZ-2.
      Prospective studies are urgently needed to elucidate the clinical and
      physiological outcomes of the various anthropometric indicators of malnutrition.

PMID- 26303860
TI  - Botanical features for identification of Gymnosporia arenicola dried leaf.
AB  - Gymnosporia arenicola Jordaan (Celastraceae) is a shrub or small tree, which
      naturally occurs in coastal sand dunes of Southern Mozambique and South Africa.
      Its dried leaf is often used in traditional medicine for the treatment of
      infectious and inflammatory diseases. Hereby, we present results of studies
      carried out according to the pharmacopoeia standards for the identification of
      herbal drugs, in the whole, fragmented, and powdered plant material. These
      results were complemented with scanning electron microscopy and histochemical
      techniques. The leaf microscopic analysis revealed a typical dorsiventral
      mesophyll with a corresponding spongy parenchyma-palisade parenchyma ratio of
      0.60, anomocytic and paracytic stomata, papillate cells with a diameter of 4.00
      +/- 0.40 um, multicellular uniseriate nonglandular trichomes with a length of
      27.00 +/- 4.10 um and cristalliferous idioblasts containing calcium oxalate
      cluster crystals with a diameter of 23.04 +/- 5.84 um. The present findings
      demonstrate that the G. arenicola leaf has both nonglandular trichomes and
      hypoderm, features not previously described in the corresponding botanical
      section (Gymnosporia sect. Buxifoliae Jordaan). The establishment of these new
      botanical markers for the identification of G. arenicola leaf is essential for
      quality, safety and efficacy reasons.

PMID- 26303861
TI  - Parabromophenacyl bromide inhibits subepithelial fibrosis by reducing TGF-beta1
      in a chronic mouse model of allergic asthma.
AB  - BACKGROUND: Our previous study showed that parabromophenacyl bromide (PBPB)
      inhibits the features of allergic airway inflammation and airway
      hyperresponsiveness (AHR). However, its effect on airway remodeling, e.g.
      subepithelial fibrosis in a chronic allergic asthma model, was not investigated.
      We examined this issue in this study. METHODS: PBPB was administered to mice with
      an induced chronic asthmatic condition. AHR was estimated at the end of the
      experiment, followed by euthanasia. Lung sections were stained with hematoxylin
      and eosin, periodic acid-Schiff and Masson's trichrome to determine airway
      inflammation, goblet cell metaplasia and subepithelial fibrosis, respectively.
      Transforming growth factor-beta1 (TGF-beta1) was estimated in lung homogenates.
      To determine the effect of PBPB on smooth-muscle hyperplasia,
      immunohistochemistry against alpha-smooth-muscle actin was performed on the lung
      sections. RESULTS: Chronic ovalbumin challenges in a mouse model of allergic
      asthma caused significant subepithelial fibrosis and elevated TGF-beta1, along
      with significant AHR. PBPB attenuated subepithelial fibrosis with a reduction of
      lung TGF-beta1, airway inflammation and AHR without affecting goblet cell
      metaplasia. It also attenuated smooth-muscle hyperplasia with a reduction in the
      expression of alpha-smooth-muscle actin in the lungs. CONCLUSION: Our findings
      indicate that PBPB attenuates some crucial features of airway remodeling such as
      subepithelial fibrosis and smooth-muscle hyperplasia. These data suggest that
      PBPB could therefore be a therapeutic drug for chronic asthma.

PMID- 26303862
TI  - Response to Letter Regarding Article, "Volatile Anesthetic-Induced Cardiac
      Protection: Molecular Mechanisms, Clinical Aspects, and Interactions With
      Nonvolatile Agents".

PMID- 26303863
TI  - Letter in Reply.

PMID- 26303865
TI  - Differences in the ARID-1 alpha expressions in squamous and adenosquamous
      carcinomas of uterine cervix.
AB  - AT-rich interactive domain 1A (ARID1A) is a tumor suppressor gene involved in
      chromatin remodeling which encodes ARID1A (BAF250a) protein. Recent studies have
      shown the loss of ARID1A expression in several types of tumors. This
      retrospective study was designed to evaluate the differences in tissue
      expressions of ARID1A in a spectrum of cervical neoplasms. Cervical
      intraepithelial neoplasms, invasive squamous or adenosquamous carcinomas were
      identified in 100 patients recently diagnosed as cervical neoplasms based on
      pathology databases. In this series, there were 29 low- and 29 high-grade
      cervical intraepithelial neoplasms, 27 squamous cell carcinomas, and 15
      adenosquamous carcinomas. Mean age of the patients was 47.8 +/- 13 years (20-80
      years). It was determined that the expression of ARID1A was statistically
      significantly down-regulated in adenosquamous carcinomas when compared with non
      invasive or invasive squamous cell carcinomas (p = 0.015). Lower levels of the
      ARID1A expression were detected in cases with adenosquamous carcinomas (60%), low
      or high-grade squamous intraepithelial lesion (SIL) (31%), and squamous cell
      carcinomas (18.5%). Our findings have demonstrated the presence of a correlation
      between ARID1A expression and adenomatous differentiation of uterine squamous
      cell carcinomas. Therefore, ARID1A gene may suggestively have a role in the
      pathogenesis of cervical adenosquamous carcinomas. 

PMID- 26303864
TI  - Ridge, Lasso and Bayesian additive-dominance genomic models.
AB  - BACKGROUND: A complete approach for genome-wide selection (GWS) involves reliable
      statistical genetics models and methods. Reports on this topic are common for
      additive genetic models but not for additive-dominance models. The objective of
      this paper was (i) to compare the performance of 10 additive-dominance predictive
      models (including current models and proposed modifications), fitted using
      Bayesian, Lasso and Ridge regression approaches; and (ii) to decompose genomic
      heritability and accuracy in terms of three quantitative genetic information
      sources, namely, linkage disequilibrium (LD), co-segregation (CS) and pedigree
      relationships or family structure (PR). The simulation study considered two broad
      sense heritability levels (0.30 and 0.50, associated with narrow sense
      heritabilities of 0.20 and 0.35, respectively) and two genetic architectures for
      traits (the first consisting of small gene effects and the second consisting of a
      mixed inheritance model with five major genes). RESULTS: G-REML/G-BLUP and a
      modified Bayesian/Lasso (called BayesA*B* or t-BLASSO) method performed best in
      the prediction of genomic breeding as well as the total genotypic values of
      individuals in all four scenarios (two heritabilities x two genetic
      architectures). The BayesA*B*-type method showed a better ability to recover the
      dominance variance/additive variance ratio. Decomposition of genomic heritability
      and accuracy revealed the following descending importance order of information:
      LD, CS and PR not captured by markers, the last two being very close.
      CONCLUSIONS: Amongst the 10 models/methods evaluated, the G-BLUP, BAYESA*B* (
      2,8) and BAYESA*B* (4,6) methods presented the best results and were found to be
      adequate for accurately predicting genomic breeding and total genotypic values as
      well as for estimating additive and dominance in additive-dominance genomic
      models.

PMID- 26303866
TI  - Using epidemiological registry data to provide background rates as context for
      adverse events in a rheumatoid arthritis drug development program: a coordinated
      approach.
AB  - PURPOSE: Observational studies can provide context for adverse events observed in
      clinical trials, especially for infrequent events or long-term risks. We
      developed methods to improve safety contextualization for a rheumatoid arthritis
      drug development program through coordinated analyses of multiple registries.
      METHODS: We identified and characterized differences and similarities across five
      registries (Swedish Rheumatology Quality of Care Register, Consortium of
      Rheumatology Researchers of North America [CORRONA], Norfolk Arthritis Register,
      Institute of Rheumatology Rheumatoid Arthritis, and the new CORRONA
      International), harmonized outcome definitions, and investigated whether
      restricted subcohorts improved comparability with trial populations. To address
      confounding, we identified risk predictors for outcomes of interest (mortality,
      cardiovascular disease, infection, and malignancy). We used patient-level
      analyses at each registry and central analysis of standardized group-level data.
      RESULTS: Despite data differences, the coordinated approach enabled consistent
      variable definitions for key baseline characteristics and outcomes. Selection of
      restricted subcohorts (e.g., using active joint count criteria) improved baseline
      comparability with trial patients for some rheumatoid arthritis disease activity
      measures, but less for other characteristics (e.g., age and comorbidity);
      however, such selection decreased sample size considerably. For most outcomes,
      age was the most important risk predictor, emphasizing the importance of age/sex
      standardization to address confounding. The prospective approach enabled use of
      recent relevant data; the distributed analysis safeguarded confidentiality of
      registry data. CONCLUSIONS: Compared with reliance on published data alone, a
      forward-looking coordinated approach across multiple observational data sources
      can improve comparability and consistency and better support sensitivity analyses
      and data interpretation, in contextualizing safety data from clinical trials.
      This approach may have utility to support safety assessments across diverse
      diseases and drug development programs and satisfy future regulatory
      requirements.

PMID- 26303867
TI  - Structural Deformation of Sm@C88 under High Pressure.
AB  - We have studied the structural transformation of Sm@C88 under pressure up to 18
      GPa by infrared spectroscopy combined with theoretical simulations. The infrared
      active vibrational modes of Sm@C88 at ambient conditions have been assigned for
      the first time. Pressure-induced blue and red shifts of the corresponding
      vibrational modes indicate an anisotropic deformation of the carbon cage upon
      compression. We propose that the carbon cage changes from ellipsoidal to
      approximately spherical around 7 GPa. A smaller deformation of the carbon bonds
      in the area close to the Sm atom in the cage suggests that the trapped Sm atom
      plays a role in minimizing the compression of the adjacent bonds. Pressure
      induced a significant reduction of the band gap of the crystal. The HOMO-LUMO gap
      of the Sm@C88 molecule decreases remarkably at 7 GPa as the carbon cage is
      deformed. Also, compression enhances intermolecular interactions and causes a
      widening of the energy bands. Both effects decrease the band gap of the sample.
      The carbon cage deforms significantly above 7 GPa, from spherical to a peanut
      like shape and collapses at 18 GPa. 

PMID- 26303868
TI  - Respiratory illness contributed significantly to morbidity in children born
      extremely premature or with extremely low birthweights in 1999-2000.
AB  - AIM: This study investigated respiratory morbidity and risk factors during the
      first five years of life after extremely preterm birth. METHODS: Paediatric
      assessments and parental questionnaires were obtained at two and five years of
      age in this national prospective cohort of 372 Norwegian children born during
      1999-2000 at a gestational age of <28 weeks or birthweight <1,000 grams. RESULTS:
      Paediatric assessments were obtained for 100% and 82% of the children at two and
      five years of age and completed questionnaires for 71% and 76%, respectively.
      Total readmission rates decreased from 49 to 14% at one to five years, and
      readmissions for respiratory causes fell from 31 to 3%. Bronchopulmonary
      dysplasia (BPD) or gestational age was not associated with readmissions for
      respiratory causes in multiple logistic regression models. However, both BPD and
      gestational age <= 25 weeks was associated with wheezing during the first year
      and the use of asthma medication during the first two years. BPD was associated
      with asthma medication between three and five years but not significantly at five
      years. CONCLUSION: Respiratory morbidity decreased during the first five years of
      life but was still more common than expected. It was unrelated to BPD and
      gestational age at five years of age.

PMID- 26303869
TI  - Inspiration amidst the challenges: the first report of successful bone marrow
      transplantation in the Himalayan country Nepal.

PMID- 26303870
TI  - Cord blood irisin levels are positively correlated with birth weight in newborn
      infants.
AB  - BACKGROUND: Irisin is a novel myokine, secreted from skeletal muscle after
      exercise. Irisin mediates exercise-related energy expenditure by turning white
      adipose tissue (WAT) into brown adipose tissue (BAT). Thus, irisin is considered
      as a potential biomarker for obesity and metabolic syndrome. Infants born small
      for gestational age (SGA) have increased risk for metabolic syndrome. However,
      the physiologic role of irisin in neonates remains to be studied. OBJECTIVE: To
      evaluate the association of umbilical cord blood irisin levels with gestational
      age and birth weight categories in neonates. METHODS: A cross-sectional study of
      341 newborns, from 26 to 41weeks' gestation. We collected umbilical cord blood
      and analyzed plasma for irisin by ELISA. RESULTS: Plasma irisin levels were
      positively correlated with gestational age (r=0.21, p<0.001), and birth weight Z
      score (r=0.18, p<0.001). SGA infants had significantly lower irisin (median
      [interquartile range] 55.38 [46.56-65.72]ng/mL) compared to appropriate for
      gestational age infants (64.41 [53.87-76.76]ng/mL) and large for gestational age
      infants (68.70 [54.78-79.09]ng/mL, p<0.01). The association between SGA and lower
      irisin remained significant in multivariate analysis independent of gestational
      age, maternal age, maternal BMI, and gestational diabetes (p=0.03). In singleton
      infants, irisin was also significantly negatively associated with maternal
      preeclampsia (p=0.01). CONCLUSIONS: Our results support the notion that irisin
      may have a physiologic role in neonates. We speculate that decreased levels of
      irisin in SGA infants may contribute to the development of catch-up growth and
      metabolic syndrome later in life.

PMID- 26303872
TI  - Physico-chemical, nutritional, and volatile composition and sensory profile of
      Spanish jujube (Ziziphus jujuba Mill.) fruits.
AB  - BACKGROUND: Jujube fruit is eaten mostly fresh, but may be dried (Chinese dates
      and tea) or processed into confectionary recipes in bread, cakes, compotes, and
      candy. Given that the quality of jujube available on the market differs on
      account of various factors such as geographical environment, cultivar, processing
      conditions, and storage conditions, and that, for consumers, flavour and
      nutrition properties of jujube represent the major parameters in determining the
      quality of jujube, the main goal of this study were to determine the main physico
      chemical properties of jujube fruits, sugars and organic acids profiles, protein,
      mineral constituents, volatile composition and sensory profile of jujube fruits.
      This would allow breeders to select cultivars with higher levels of nutrients and
      also enable increasing dietary intake by consumers. RESULTS: Investigations
      showed that jujube fruit weight ranged from 4.8 to 29.3 g fruit(-1) . Four sugars
      (glucose, fructose, sucrose and sorbitol) and four organic acids (citric, malic,
      ascorbic and succinic acids) were identified and quantified by high-performance
      liquid chromatography in jujube fruits. Potassium, calcium and magnesium were the
      major mineral constituents in jujube fruits. Fifteen volatiles compounds were
      found in the aroma profile of jujube fruits (nine were aldehydes, three terpenes,
      one ester, one ketone and one linear hydrocarbon). CONCLUSION: The results showed
      that Spanish jujube cultivars studied are a good source of vitamin C, and they
      have a low content of Na. The jujube cultivar with the most appreciated quality
      by consumers was GAL; the GAL fruits were sweet, crunchy, and had high
      intensities of jujube ID and apple flavour a long after-taste. Therefore, jujube
      grown in Spain has a great potential to be exploited for functional foods. (c)
      2015 Society of Chemical Industry.

PMID- 26303871
TI  - Interaction between metformin and leucine in reducing hyperlipidemia and hepatic
      lipid accumulation in diet-induced obese mice.
AB  - BACKGROUND: Leucine stimulates Sirt1 and AMPK signaling in vitro and in vivo.
      Since metformin converges on the same pathway, we have tested the ability of
      leucine to amplify the effects of metformin on AMPK-mediated hepatic lipid
      metabolism in diet-induced-obese insulin-resistant mice. METHODS: Mice were fed
      high leucine (24 g/kg diet) with or without sub-therapeutic levels of metformin
      (0.05-0.50 g/kg diet) or therapeutic levels of metformin (1.5 g/kg diet; ~300
      mg/kg body weight). RESULTS: High-fat diet produced a 10-fold increase in
      inguinal fat pad weight and 25% increase in liver weight, histologically
      confirmed as steatosis. The leucine-metformin combinations reduced fat pad mass,
      normalized liver weight, liver and plasma lipids and inflammatory markers
      (interleukin 6, interleukin 1 beta, tumor necrosis factor alpha, monocyte
      chemotactic protein-1, C-reactive protein) comparable to the effects of
      therapeutic metformin. Moreover, the highest sub-therapeutic levels of metformin
      with leucine exerted significantly greater effects than therapeutic levels of
      metformin and fully reversed hepatic steatosis. These effects were mediated by
      upregulation of hepatic AMPK and associated changes in lipogenic gene expression
      (fatty acid synthase, stearoyl CoA desaturase, acetyl CoA carboxylase) in the
      liver. CONCLUSION: A low-dose leucine-metformin combination exerts comparable
      effects on adiposity to therapeutic doses of metformin and fully reverses hepatic
      steatosis in diet-induced-obese mice.

PMID- 26303873
TI  - The Extent and Prediction of Heavy Metal Pollution in Soils of Shahrood and
      Damghan, Iran.
AB  - The levels of 12 heavy metals (Ag, Ba, Be, Cd, Co, Cr, Cu, Ni, Pb, Tl, V, Zn)
      were considered in 229 soil samples in Semnan Province, Iran. To discriminate
      between natural and anthropogenic inputs of heavy metals, factor analysis was
      used. Seven factors accounting for 90.5 % of the total variance were extracted.
      The mining and agricultural activities along with geogenic sources have been
      attributed as the main causes of the levels of heavy metals in the study area.
      The partial least squares regression was utilized to predict the level of soil
      pollution index (SPI) considering the concentrations of 12 heavy metals. The
      eigenvectors from the first three PLS represented more than 98 % of the overall
      variance. The correlation coefficient between the observed and predicted SPI was
      0.99 indicating the high efficiency of this method. The resultant coefficient of
      determination for three PLS components was 0.984 confirming the predictive
      ability of this method. 

PMID- 26303874
TI  - Protective immunity of a Pichia pastoris expressed recombinant iridovirus major
      capsid protein in the Chinese giant salamander, Andrias davidianus.
AB  - The major capsid protein (MCP) is the main immunogenic protein of iridoviruses,
      that has been widely used as an immunogen in vaccination trials. In this study,
      the codon-optimized giant salamander iridovirus (GSIV) MCP gene (O-MCP) was
      synthesized and cloned into a pPICZalpha B vector for secretory expression in the
      methylotrophic yeast Pichia pastoris after methanol induction. The expression of
      the O-MCP protein was detected by the Bradford protein assay, SDS-PAGE, Western
      blotting and electron microscopy. The Bradford protein assay indicated that the
      concentration of the O-MCP expressed was about 40 MUg/ml in culture supernatants.
      SDS-PAGE analysis revealed that the O-MCP had a molecular weight of about 66 kDa
      and reacted with a His-specific MAb that was confirmed by Western blotting.
      Electron microscopy observations revealed that the purified O-MCP could self
      assemble into virus-like particles. Healthy giant salamanders were vaccinated by
      intramuscular injection with the O-MCP antigen at a dose of 20 MUg/individual.
      The numbers of erythrocytes and leukocytes in the peripheral blood of immunized
      Chinese giant salamanders increased significantly at day 3 and reached a peak at
      day 5 post-immunization. Meanwhile, the differential leukocyte counts of
      monocytes and neutrophils increased significantly at day 5 post-immunization
      compared to that of the control group. The percentage of lymphocytes was 71.33 +/
      3.57% at day 21 post-immunization. The neutralization assay showed that the
      serum neutralizing antibody titer reached 321 at day 21 post-immunization. The
      GSIV challenge test revealed that the relative percent survival of Chinese giant
      salamanders vaccinated with O-MCP was 78%. These results indicated that the O-MCP
      antigen expressed by the Pichia pastoris system elicited significant immune
      response in the Chinese giant salamander against GSIV and might represent a
      potential yeast-derived vaccine candidate that could be used for the control of
      disease caused by the giant salamander iridovirus.

PMID- 26303875
TI  - Cost effectiveness evaluation of a rotavirus vaccination program in Argentina.
AB  - BACKGROUND: Rotavirus diarrhea is one of the most important vaccine-preventable
      causes of severe diarrhea in children worldwide. There are two live-attenuated
      virus vaccines licensed, Rotarix (RV1) a monovalent vaccine by GlaxoSmithKline
      and a pentavalent vaccine, RotaTeq(RV5), by Merck & Co., with similar results.
      This study aim was to evaluate the cost-effectiveness of the utilization of RV1
      compared with RV5 in Argentina. METHODS: A deterministic Markov model based on
      the lifetime follow up of a static cohort was used. Quality Adjusted Life Years
      (QALYs) as a measure of results, the perspective of the health care system and a
      5% discount rate for health benefits and costs has been used. A review of the
      literature to obtain epidemiologic and resources utilization of rotavirus
      diarrhea was performed. The sources used to estimate epidemiologic parameters
      were the National Health Surveillance System, the national mortality statistics
      and national database of hospital discharges records. Costs were obtained from
      different health subsectors and are expressed in local currency. RESULTS: Both
      vaccination alternatives were less costly and more effective than the strategy
      without vaccination (total costs $ 69,700,645 and 2575 total QALYs lost). When
      comparing RV1 vs. RV5, RV1 was less expensive ($ 60,174,508 vs. $ 67,545,991
      total costs) and more effective (1105 vs. 1213 total QALYs lost) than RV5, RV1
      being therefore a dominating strategy. Probabilistic sensitivity analysis showed
      results to be robust with a 100% probability of being cost-effective at a WTP
      threshold of 1 GDP per capita when comparing the RV1 vs. no vaccination.
      CONCLUSION: Both RV1 and RV5 schedules dominate the no vaccination strategy and
      RV5 was dominated by RV1. This information is a valuable input regarding the
      incorporation of this kind of vaccines into the national vaccination programs.

PMID- 26303876
TI  - Polio eradication in the African Region on course despite public health
      emergencies.
AB  - The World Health Organization, African Region is heading toward eradication of
      the three types of wild polio virus, from the Region. Cases of wild poliovirus
      (WPV) types 2 and 3 (WPV2 and WPV3) were last reported in 1998 and 2012,
      respectively, and WPV1 reported in Nigeria since July 2014 has been the last in
      the entire Region. This scenario in Nigeria, the only endemic country, marks a
      remarkable progress. This significant progress is as a result of commitment of
      key partners in providing the much needed resources, better implementation of
      strategies, accountability, and innovative approaches. This is taking place in
      the face of public emergencies and challenges, which overburden health systems of
      countries and threaten sustainability of health programmes. Outbreak of Ebola and
      other diseases, insecurity, civil strife and political instability led to
      displacement of populations and severely affected health service delivery. The
      goal of eradication is now within reach more than ever before and countries of
      the region should not relent in their efforts on polio eradication. WHO and
      partners will redouble their efforts and introduce better approaches to sustain
      the current momentum and to complete the job. The carefully planned withdrawal of
      oral polio vaccine type II (OPV2) with an earlier introduction of one dose of
      inactivated poliovirus vaccine (IPV), in routine immunization, will boost
      immunity of populations and stop cVDPVs. Environmental surveillance for polio
      viruses will supplement surveillance for AFP and improve sensitivity of detection
      of polio viruses.

PMID- 26303877
TI  - Universal scaling of crowding-induced DNA mobility is coupled with topology
      dependent molecular compaction and elongation.
AB  - Using single-molecule fluorescence microscopy and particle-tracking techniques,
      we elucidate the role DNA topology plays in the diffusion and conformational
      dynamics of crowded DNA molecules. We focus on large (115 kbp), double-stranded
      ring and linear DNA crowded by varying concentrations (0-40%) of dextran (10, 500
      kDa) that mimic cellular conditions. By tracking the center-of-mass and measuring
      the lengths of the major and minor axes of single DNA molecules, we characterize
      both DNA mobility reduction as well as crowding-induced conformational changes
      (from random spherical coils). We reveal novel topology-dependent conformations,
      with single ring molecules undergoing compaction to ordered spherical
      configurations ~20% smaller than dilute random coils, while linear DNA elongates
      by ~2-fold. Surprisingly, these highly different conformations result in nearly
      identical exponential mobility reduction dependent solely on crowder volume
      fraction Phi, revealing a universal critical crowding concentration of Phic? 2.3.
      Beyond Phic DNA exhibits topology-independent conformational relaxation dynamics
      despite highly distinct topology-driven conformations. Our collective results
      reveal that topology-dependent conformational changes, unique to crowded
      environments, enable DNA to overcome the classically expected mobility reduction
      that high-viscosity crowded environments impose. Such coupled universal dynamics
      suggest a mechanism for DNA to maintain sufficient mobility required for wide
      ranging biological processes despite severe cellular crowding. 

PMID- 26303878
TI  - Proteome Profiles of Outer Membrane Vesicles and Extracellular Matrix of
      Pseudomonas aeruginosa Biofilms.
AB  - In the present work, two different proteomic platforms, gel-based and gel-free,
      were used to map the matrix and outer membrane vesicle exoproteomes of
      Pseudomonas aeruginosa PAO1 biofilms. These two proteomic strategies allowed us a
      confident identification of 207 and 327 proteins from enriched outer membrane
      vesicles and whole matrix isolated from biofilms. Because of the physicochemical
      characteristics of these subproteomes, the two strategies showed complementarity,
      and thus, the most comprehensive analysis of P. aeruginosa exoproteome to date
      was achieved. Under our conditions, outer membrane vesicles contribute
      approximately 20% of the whole matrix proteome, demonstrating that membrane
      vesicles are an important component of the matrix. The proteomic profiles were
      analyzed in terms of their biological context, namely, a biofilm. Accordingly
      relevant metabolic processes involved in cellular adaptation to the biofilm
      lifestyle as well as those related to P. aeruginosa virulence capabilities were a
      key feature of the analyses. The diversity of the matrix proteome corroborates
      the idea of high heterogeneity within the biofilm; cells can display different
      levels of metabolism and can adapt to local microenvironments making this
      proteomic analysis challenging. In addition to analyzing our own primary data, we
      extend the analysis to published data by other groups in order to deepen our
      understanding of the complexity inherent within biofilm populations. 

PMID- 26303879
TI  - An Overview of the CDC's Community-Based Breastfeeding Supplemental Cooperative
      Agreement.

PMID- 26303880
TI  - Multiple primary melanoma in the elderly.
AB  - BACKGROUND: Few data exist regarding surveillance for multiple primary melanoma
      (MPM) in elderly patients or whether the incidence and risk factors are the same
      as for younger patients. Thus, we studied the frequency and characteristics of
      MPM in the elderly melanoma patients. METHODS: From our prospective melanoma
      registry, we studied 222 consecutive patients aged 65 years or older at their
      initial melanoma diagnosis. Mean follow-up was 65 +/- 3 months. RESULTS: Median
      age was 76 years. Twenty-two patients (10%) developed a second primary melanoma
      and 8 (4%) of 3 or more primaries. 82% of second primaries (18 of 22) were the
      same or thinner than the index melanoma, yet 50% of third primary melanomas (4
      out of 8) were thicker. Only prior dysplastic nevi (P <. 0001) were a significant
      risk factor for MPM. CONCLUSIONS: These data suggest elderly melanoma patients
      have a significant risk of MPM that warrants careful surveillance to facilitate
      prompt detection and treatment. Patients with dysplastic nevi merit special
      scrutiny.

PMID- 26303881
TI  - Comparative effectiveness of treatment strategies for severe splenic trauma in
      the pediatric population.
AB  - BACKGROUND: Splenic angioembolization (SAE) is increasingly used in the
      management of splenic injuries in adults, although its value in pediatric trauma
      is unclear. We sought to assess outcomes related to splenectomy vs SAE. METHODS:
      The National Trauma Data Bank was queried for patients 0 to 15 years of age from
      2007 to 2011. Subgroup analysis of splenectomy vs SAE was performed for high
      grade injuries using propensity analysis and inverse probability weighting.
      RESULTS: Of 11,694 children presenting with splenic trauma, over 90% were treated
      nonoperatively. Adjusted analysis of high-grade injuries included 265 children
      who underwent splenectomy and 199 who underwent SAE. The Injury Severity Score,
      number of transfusions, and complications rates were not significantly different
      between the 2 groups. Overall adjusted mortality for children with high-grade
      injuries was 13.4% following splenectomy and 10.0% following SAE (P = .31)
      CONCLUSION: Patients undergoing SAE for high-grade splenic trauma have comparable
      morbidity and mortality with splenectomy.

PMID- 26303882
TI  - Laparoscopic adjustable gastric banding: efficacy and consequences over a 13-year
      period.
AB  - BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) is a common bariatric
      surgery. Although it is a safe and effective method of weight reduction in short
      term, it may result in some problems in long term. The purpose of this study was
      to investigate the consequences of LAGB in long term among morbid obese patients.
      METHODS: In this prospective study, 80 patients underwent LAGB using pars
      flaccida technique from 2001 to 2006. Long-term postoperative consequences and
      complications of these patients were recorded. RESULTS: The preoperative mean
      values of weight and body mass index were 125.5 +/- 22.5 kg and 44.5 +/- 6.5
      kg/m(2), respectively. Over the 13-year follow-up period, 56 patients (84.8%)
      experienced at least one complication. The most common complications were band
      erosion (20 patients) and weight regains (13 patients). Fifty-one patients
      (78.5%) required reoperation. The band of 48 patients (72.7%) was removed; of
      these, twenty patients (30.3%) underwent other bariatric surgeries. Percent of
      excess weight loss was 47.1% +/- 30.1%, and the success rate was 48.7%.
      CONCLUSIONS: LAGB is a successful method with low complications in short term;
      however, over long term, it results in various complications.

PMID- 26303884
TI  - Gestural abilities of children with specific language impairment.
AB  - BACKGROUND: Specific language impairment (SLI) is diagnosed when language is
      significantly below chronological age expectations in the absence of other
      developmental disorders, sensory impairments or global developmental delays. It
      has been suggested that gesture may enhance communication in children with SLI by
      providing an alternative means to convey words or extend utterances. However,
      gesture is a complex task that requires the integration of social, cognitive and
      motor skills, skills that some children with SLI may find challenging. In
      addition, there is reason to believe that language and gesture form an integrated
      system leading to the prediction that children with a SLI may also have
      difficulties with gestural communication. AIMS: To explore the link between
      language and gesture in children with poor language skills. METHODS & PROCEDURE:
      Fifteen children with SLI and 14 age-matched typically developing children (TD)
      participated in this study. The children completed measures of expressive and
      receptive vocabulary, non-verbal cognition, motor control, gesture comprehension
      and gesture production. OUTCOMES & RESULTS: TD children achieved significantly
      higher scores on measures of gesture production and gesture comprehension
      relative to children with SLI. Significant correlations between both measures of
      vocabulary and both measures of gesture suggest a tight link between language and
      gesture. CONCLUSIONS & IMPLICATIONS: The findings support the idea that gesture
      and language form one integrated communication system, rather than two separate
      communication modalities. This implies that children with SLI may have underlying
      deficits that impact not only on language but also on gesture production and
      comprehension.

PMID- 26303886
TI  - Therapeutics targeting inflammation in the immune reconstitution inflammatory
      syndrome.
AB  - Immune reconstitution inflammatory syndrome (IRIS) is characterized by
      improvement in a previously incompetent human immune system manifesting as
      worsening of clinical symptoms secondary to the ability of the immune system to
      now mount a vigorous inflammatory response. IRIS was first recognized in the
      setting of human immunodeficiency virus, and this clinical setting continues to
      be where it is most frequently encountered. Hallmarks of the pathogenesis of
      IRIS, independent of the clinical presentation and the underlying pathogen,
      include excessive activation of the immune system, with increased circulating
      effector memory T cells, and elevated levels of serum cytokines and inflammatory
      markers. Patients with undiagnosed opportunistic infections remain at risk for
      unmasking IRIS at the time of active antiretroviral therapy (ART) initiation.
      Systematic screening for opportunistic infections before starting ART is a key
      element to prevent this phenomenon. Appropriate management of IRIS requires
      prompt recognition of the syndrome and exclusion of alternative diagnoses,
      particularly underlying infections and drug resistance. Controlled studies
      supporting the use of pharmacologic interventions in IRIS are scare, and
      recommendations are based on case series and expert opinions. The only controlled
      trial published to date, showed reduction in morbidity in patients with
      paradoxical tuberculosis-related IRIS with the use of oral corticosteroids. There
      are currently limited data to recommend other anti-inflammatory or
      immunomodulatory therapies that are discussed in this review, and further
      research is needed. Ongoing research regarding the immune pathogenesis of IRIS
      will likely direct future rational therapeutic approaches and clinical trials.

PMID- 26303885
TI  - Autonomic Dysregulation as a Therapeutic Target for Acute HF.
AB  - OPINION STATEMENT: Despite major advances that have led to effective therapeutic
      modalities for the treatment of heart failure (HF), this syndrome has continued
      to be a staggering health problem associated with significant mortality and
      morbidity. The increasing number of hospital admissions and readmissions related
      to acute HF continues to pose a fiscal challenge leading to constant interest in
      development of novel approaches. These point to multiple areas of unmet needs
      especially in acute HF, thus, necessitating further efforts to develop novel
      strategies for prevention and treatment of acute HF. One area of continuing focus
      is targeting the role of autonomic imbalance associated with the development of
      HF. Autonomic dysregulation, manifested by increased sympathetic drive and
      reduced parasympathetic activity, has been recognized as a mediator of increased
      mortality and morbidity in HF and myocardial infarction. Furthermore, vagal
      withdrawal has been shown to precede acute decompensation, though whether this
      represents cause or effect is unknown. This review discusses the potential role
      of autonomic dysregulation as a therapeutic modality for patients with acute
      decompensated HF.

PMID- 26303887
TI  - Thermoactivatable polymer-grafted liposomes for low-invasive image-guided
      chemotherapy.
AB  - The objective of this study was to develop a thermotriggered, polymer-based
      liposomal drug carrier with an activatable magnetic resonance imaging (MRI)
      contrast property for monitoring the release of substances and for localized
      tumor therapy. The multimodal thermoactivatable polymer-grafted liposomes (MTPLs)
      were tested to investigate whether the accumulation of MTPLs in colon-26 grafted
      tumors could be visualized in vivo using MRI and optical imaging, whether MTPLs
      induce signal enhancement, reflecting the release of their contents, after
      triggering by short-term heating (42.5 degrees C for 10 minutes) 9 hours after
      MTPL administration (late-phase triggering), and whether MTPLs can provide a
      sufficient antitumor effect. The imaging and therapeutic properties of MTPLs were
      tested both in vitro and in vivo (BALB/c nude mice: heated group with MTPLs (n =
      5), nonheated group with MTPLs (n = 5), heated group with doxorubicin-free MTPLs
      (n = 5), nonheated group with manganese-free MTPLs (n = 5), and kinetics
      observation group (n = 3); N = 23). Through in vivo MRI and fluorescent imaging,
      the MTPLs were shown to have significantly accumulated in the grafted colon-26
      tumors 8 hours after administration. Delayed thermotriggering (9 hours after
      administration) caused MR signal enhancement, reflecting the release of their
      contents, after a short exposure to tolerable heat. In addition, significant
      antitumor effects were observed after treatment. The proposed polymer-based
      activatable MTPLs with a "delayed thermotrigger" provide a promising technology
      for cancer theranostics that allows minimal adverse effects and rapid interactive
      therapy.

PMID- 26303888
TI  - Differential effects of N-acetyl-aspartyl-glutamate on synaptic and extrasynaptic
      NMDA receptors are subunit- and pH-dependent in the CA1 region of the mouse
      hippocampus.
AB  - Ischemic strokes cause excessive release of glutamate, leading to overactivation
      of N-methyl-d-aspartate receptors (NMDARs) and excitotoxicity-induced neuronal
      death. For this reason, inhibition of NMDARs has been a central focus in
      identifying mechanisms to avert this extensive neuronal damage. N-acetyl-aspartyl
      glutamate (NAAG), the most abundant neuropeptide in the brain, is neuroprotective
      in ischemic conditions in vivo. Despite this evidence, the exact mechanism
      underlying its neuroprotection, and more specifically its effect on NMDARs, is
      currently unknown due to conflicting results in the literature. Here, we uncover
      a pH-dependent subunit-specific action of NAAG on NMDARs. Using whole-cell
      electrophysiological recordings on acute hippocampal slices from adult mice and
      on HEK293 cells, we found that NAAG increases synaptic GluN2A-containing NMDAR
      EPSCs, while effectively decreasing extrasynaptic GluN2B-containing NMDAR EPSCs
      in physiological pH. Intriguingly, the results of our study further show that in
      low pH, which is a physiological occurrence during ischemia, NAAG depresses
      GluN2A-containing NMDAR EPSCs and amplifies its inhibitory effect on GluN2B
      containing NMDAR EPSCs, as well as upregulates the surface expression of the
      GluN2A subunit. Altogether, our data demonstrate that NAAG has differential
      effects on NMDAR function based on subunit composition and pH. These findings
      suggest that the role of NAAG as a neuroprotective agent during an ischemic
      stroke is likely mediated by its ability to reduce NMDAR excitation. The
      inhibitory effect of NAAG on NMDARs and its enhanced function in acidic
      conditions make NAAG a prime therapeutic agent for the treatment of ischemic
      events. 

PMID- 26303890
TI  - Self-reported postpartum morbidity: prevalence and determinants among women in
      Marrakesh, Morocco.
AB  - BACKGROUND: Maternal mortality is a public health problem particularly in
      developing countries. This is mainly related to maternal morbidity, especially
      during the post-partum period (Haemorrhage, infections...). In Morocco, little is
      known about maternal morbidity within the population. The aim of this study is to
      determine the prevalence of self-reported postpartum morbidity and grasp its
      determinants. METHODS: This descriptive and analytic cross-sectional survey was
      carried out in six health centers drawn randomly in Marrakesh, Morocco. A total
      of 1,029 women of reproductive age (15-49) giving birth in the year preceding the
      survey were enrolled. Women were examined in these health centers during the
      study period. A questionnaire gathered information about socio-demographic,
      health and reported postpartum morbidity. Bivariate and multiple analyses were
      used to identify associated factors with the self-reported postpartum morbidity.
      Statistical significance was set at p < 0.05. RESULTS: The self-reported
      postpartum morbidity prevalence was 13.1% while haemorrhage, pregnancy-induced
      hypertension and fever were the main complications: 71.92%; 12.18% and 10.64%
      respectively. According to the multiple logistic regression model, the illiteracy
      among women and the number of pregnancies greater than 3 determine independently
      this morbidity (OR = 1.24; CI 95%: 1.09-1.54; and OR = 1.69; CI 95%:1.04-2.70
      respectively). CONCLUSION: Reducing female illiteracy and fertility will help the
      fight against postpartum maternal morbidity, which is critical to the wellbeing
      of women and their infants.

PMID- 26303891
TI  - Tear staining in pigs: a potential tool for welfare assessment on commercial
      farms.
AB  - Tear staining or chromodacryorrhea refers to a dark stain below the inner corner
      of the eye, caused by porphyrin-pigmented secretion from the Harderian gland. It
      has been shown to be a consistent indicator of stress in rats and to correlate
      with social stress and a barren environment in pigs. The current study was, to
      our knowledge, the first to test it on commercial pig farms as a potential
      welfare indicator. The study was carried out on three commercial farms in
      Finland, in connection to a larger study on the effects of different types of
      manipulable objects on tail and ear biting and other behavioural parameters. Farm
      A was a fattening farm, on which 768 growing-finishing pigs were studied in 73
      pens. Farm B had a fattening unit, in which 656 growing-finishing pigs were
      studied in 44 pens, and a farrowing unit, in which 29 sows and their litters
      totalling 303 piglets were studied in 29 pens. Farm C was a piglet-producing
      farm, on which 167 breeder gilts were studied in 24 pens. Data collection
      included individual-level scoring of tear staining; scoring of tail and ear
      damage in the growing-finishing pigs and breeder gilts; a novel object test for
      the piglets; and a novel person test for the growing-finishing pigs on Farm B and
      the breeder gilts on Farm C. On Farm A, tear staining was found to correlate with
      tail damage scores (n=768, rs=0.14, P<0.001) and ear damage scores (n=768,
      rs=0.16, P<0.001). In the growing-finishing pigs on Farm B, tear staining of the
      left eye correlated with tail damage (n=656, rs=0.12, P<0.01) and that of the
      right eye correlated with ear damage (n=656, rs=0.10, P<0.01). On Farm A, tear
      staining sores were lower in the treatment with three different types of
      manipulable objects as compared with controls (mean scores 3.3 and 3.9,
      respectively, n=31, F29=4.2, P<0.05). In the suckling piglets on Farm B, tear
      staining correlated with the latency to approach a novel object (n=29, rp=0.41,
      P<0.05). Although correlations with tail and ear damage were low, it was
      concluded that tear staining has promising potential as a new, additional welfare
      indicator for commercial pig farming. Further research is needed on the
      mechanisms of tear staining.

PMID- 26303892
TI  - Alternation as a form of allocation for quality improvement studies in primary
      healthcare settings: the on-off study design.
AB  - BACKGROUND: Randomized controlled trials are considered the "gold standard" for
      scientific rigor in the assessment of benefits and harms of interventions in
      healthcare. They may not always be feasible, however, when evaluating quality
      improvement interventions in real-world healthcare settings. Non-randomized
      controlled trials (NCTs) are designed to answer questions of effectiveness of
      interventions in routine clinical practice to inform a decision or process. The
      on-off NCT design is a relatively new design where participant allocation is by
      alternation. In alternation, eligible patients are allocated to the intervention
      "on" or control "off " groups in time series dependent sequential clusters.
      METHODS: We used two quality improvement studies undertaken in a Canadian primary
      care setting to illustrate the features of the on-off design. We also explored
      the perceptions and experiences of healthcare providers tasked with implementing
      the on-off study design. RESULTS AND DISCUSSION: The on-off design successfully
      allocated patients to intervention and control groups. Imbalances between
      baseline variables were attributed to chance, with no detectable biases. However,
      healthcare providers' perspectives and experiences with the design in practice
      reveal some conflict. Specifically, providers described the process of allocating
      patients to the off group as unethical and immoral, feeling it was in direct
      conflict with their professional principle of providing care for all. The degree
      of dissatisfaction seemed exacerbated by: 1) the patient population involved
      (e.g., patient population viewed as high-risk (e.g., depressed or suicidal)), 2)
      conducting assessments without taking action (e.g., administering the PHQ-9 and
      not acting on the results), and 3) the (non-blinded) allocation process.
      CONCLUSIONS: Alternation, as in the on-off design, is a credible form of
      allocation. The conflict reported by healthcare providers in implementing the
      design, while not unique to the on-off design, may be alleviated by greater
      emphasis on the purpose of the research and having research assistants allocate
      patients and collect data instead of the healthcare providers implementing the
      trial. In addition, consultation with front-line staff implementing the trials
      with an on-off design on appropriateness to the setting (e.g., alignment with
      professional values and the patient population served) may be beneficial. TRIAL
      REGISTRATION: Health Eating and Active Living with Diabetes: ClinicalTrials.gov
      identifier: NCT00991380. Date registered: 7 October 2009. Controlled trial of a
      collaborative primary care team model for patients with diabetes and depression:
      Clintrials.gov Identifier: NCT01328639 Date registered: 30 March 2011.

PMID- 26303893
TI  - A novel series of indazole-/indole-based glucagon receptor antagonists.
AB  - A novel, potent series of glucagon receptor antagonists (GRAs) was discovered.
      These indazole- and indole-based compounds were designed on an earlier pyrazole
      based GRA lead MK-0893. Structure-activity relationship (SAR) studies were
      focused on the C3 and C6 positions of the indazole core, as well as the benzylic
      position on the N-1 of indazole. Multiple potent GRAs were identified with
      excellent in vitro profiles and good pharmacokinetics in rat. Among them, GRA 16d
      was found to be orally active in blunting glucagon induced glucose excursion in
      an acute glucagon challenge model in glucagon receptor humanized (hGCGR) mice at
      1, 3 and 10mg/kg (mpk), and significantly lowered acute glucose levels in hGCGR
      ob/ob mice at 3 mpk dose.

PMID- 26303894
TI  - Nanoparticle-encapsulated P2X7 receptor antagonist in a pH-sensitive polymer as a
      potential local drug delivery system to acidic inflammatory environments.
AB  - We have developed nanoparticles of anti-inflammatory P2X7 receptor antagonist
      encapsulated in a pH-sensitive polymer, poly(tetrahydropyran-2-yl methacrylate)
      (poly(THPMA)), as a potential local drug delivery system to target to acidic
      inflammatory environments, in which P2X7 receptors are implicated in the
      pathology of inflammation via the activation of immune cells. The nanoparticles
      were prepared using single emulsion methods, also their size and shape were
      confirmed by microscopy and spectroscopy, etc. The profiles of the pH-dependent
      degradation, release of antagonist and biological activities were investigated.
      The nanoparticles that encapsulated the 3,5-dichloropyridine derivative (2) with
      poly(THPMA), were observed to be more slowly cleaved than the blank
      nanoparticles. Moreover, the free P2X7 receptor antagonists potently inhibited
      the receptor activation, whereas the nanoparticles of the 3,5-dichloropyridine
      derivative (2) encapsulated poly(THPMA) exhibited much lower P2X7 antagonistic
      activity through sustained encapsulation. Thus, the nanoparticles of the 3,5
      dichloropyridine derivative (2) encapsulated poly(THPMA) may be utilized to
      develop a pH-sensitive local drug delivery system for controlled release of anti
      inflammatory therapeutics in acidic physiological environments. 

PMID- 26303889
TI  - The relationship between iron dyshomeostasis and amyloidogenesis in Alzheimer's
      disease: Two sides of the same coin.
AB  - The dysregulation of iron metabolism in Alzheimer's disease is not accounted for
      in the current framework of the amyloid cascade hypothesis. Accumulating evidence
      suggests that impaired iron homeostasis is an early event in Alzheimer's disease
      progression. Iron dyshomeostasis leads to a loss of function in several enzymes
      requiring iron as a cofactor, the formation of toxic oxidative species, and the
      elevated production of beta-amyloid proteins. Several common genetic
      polymorphisms that cause increased iron levels and dyshomeostasis have been
      associated with Alzheimer's disease but the pathoetiology is not well understood.
      A full picture is necessary to explain how heterogeneous circumstances lead to
      iron loading and amyloid deposition. There is evidence to support a causative
      interplay between the concerted loss of iron homeostasis and amyloid plaque
      formation. We hypothesize that iron misregulation and beta-amyloid plaque
      pathology are synergistic in the process of neurodegeneration and ultimately
      cause a downward cascade of events that spiral into the manifestation of
      Alzheimer's disease. In this review, we amalgamate recent findings of brain iron
      metabolism in healthy versus Alzheimer's disease brains and consider unique
      mechanisms of iron transport in different brain cells as well as how disturbances
      in iron regulation lead to disease etiology and propagate Alzheimer's pathology. 

PMID- 26303895
TI  - Design, synthesis, pharmacological characterization of a fluorescent agonist of
      the P2Y14 receptor.
AB  - The P2Y14R is a G(i/o)-coupled receptor of the P2Y family of purinergic receptors
      that is activated by extracellular UDP and UDP-glucose (UDPG). In an earlier
      report we described a P2Y14R fluorescent probe, MRS4174, based on the potent and
      selective antagonist PPTN, a naphthoic acid derivative. Here, we report the
      design, preparation, and activity of an agonist-based fluorescent probe MRS4183
      (11) and a shorter P2Y14R agonist congener, which contain a UDP-glucuronic acid
      pharmacophore and BODIPY fluorophores conjugated through diaminoalkyl linkers.
      The design relied on both docking in a P2Y14R homology model and established
      structure activity relationship (SAR) of nucleotide analogs. 11 retained P2Y14R
      potency with EC50 value of 0.96 nM (inhibition of adenylyl cyclase), compared to
      parent UDPG (EC50 47 nM) and served as a tracer for microscopy and flow
      cytometry, displaying minimal nonspecific binding. Binding saturation analysis
      gave an apparent binding constant for 11 in whole cells of 21.4+/-1.1 nM, with a
      t1/2 of association at 50 nM 11 of 23.9 min. Known P2Y14R agonists and PPTN
      inhibited cell binding of 11 with the expected rank order of potency. The success
      in the identification of a new P2Y14R fluorescent agonist with low nonspecific
      binding illustrates the advantages of rational design based on recently
      determined GPCR X-ray structures. Such conjugates will be useful tools in
      expanding the SAR of this receptor, which still lacks chemical diversity in its
      collective ligands.

PMID- 26303896
TI  - The molecular fingerprint of lung inflammation after blunt chest trauma.
AB  - BACKGROUND: After severe blunt chest trauma, the development of an acute lung
      injury (ALI) is often associated with severe or even lethal complications.
      Especially in multiple injured patients after blunt chest trauma ALI/ARDS [acute
      respiratory distress syndrome (ARDS)] is frequent. However, in the initial
      posttraumatic phase, inflammatory clinical signs are often not apparent and
      underlying changes in gene-expression profile are unknown. METHODS: Therefore,
      inflammation in lung tissue following blunt chest trauma was characterized in a
      well-defined bilateral lung injury model. Using DNA microarrays representing 9240
      genes, the temporal sequence of blunt chest trauma-induced gene-expression
      patterns in lung tissue was examined. RESULTS: The results suggest an activation
      of a highly complex transcriptional program in response to chest trauma. Chest
      trauma led to elevated expression levels of inflammatory and coagulatory proteins
      (such as TNFalpha receptor, IL-1alpha, IL-1beta, C3, NF-kappaB and plasminogen
      activator). However, upregulation of proteins was found, usually incoherent of
      exerting effects in blunt thoracic trauma (pendrin, resistin, metallothionein and
      glucocorticoid-induced leucine zipper). Furthermore, significant downregulation
      was observed as early as 10 min after trauma for cytokines and complement factors
      (LCR-1, C4) as well as for intracellular signaling molecules (inhibitory protein
      phosphatase) and ion-channels (voltage-dependent Ca(2+) channel). CONCLUSIONS:
      Taken together, the provided global perspective of the inflammatory response
      following blunt chest trauma could provide a molecular framework for future
      research in trauma pathophysiology.

PMID- 26303897
TI  - Megaprimer-mediated capsid swapping for the construction of custom-engineered
      chimeric foot-and-mouth disease virus.
AB  - Foot-and-mouth disease (FMD) is a highly contagious, economically important
      disease of transboundary importance. Regular vaccination with chemically
      inactivated FMD vaccine is the major means of controlling the disease in endemic
      countries like India. However, the selection of appropriate candidate vaccine
      strain and its adaptation in cell culture to yield high titer of virus is a
      cumbersome process. An attractive approach to circumvent this tedious process is
      to replace the capsid coding sequence of an infectious full-genome length cDNA
      clone of a good vaccine strain with those of appropriate field strain, to produce
      custom-made chimeric FMD virus (FMDV). Nevertheless, the construction of chimeric
      virus can be difficult if the necessary endonuclease restriction sites are
      unavailable or unsuitable for swapping of the capsid sequence. Here we described
      an efficient method based on megaprimer-mediated capsid swapping for the
      construction of chimeric FMDV cDNA clones. Using FMDV vaccine strain A IND
      40/2000 infectious clone (pA(40/2000)) as a donor plasmid, we exchanged the
      capsid sequence of pA(40/2000) with that of the viruses belonging to serotypes O
      (n = 5), A (n = 2), and Asia 1 (n = 2), and subsequently generated infectious
      FMDV from their respective chimeric cDNA clones. The chimeric viruses exhibited
      comparable infection kinetics, plaque phenotypes, antigenic profiles, and virion
      stability to the parental viruses. The results from this study suggest that
      megaprimer-based reverse genetics technology is useful for engineering chimeric
      vaccine strains for use in the control and prevention of FMD in endemic
      countries.

PMID- 26303898
TI  - A novel gemycircularvirus from experimental rats.
AB  - Recently, gemycircularviruses have been found in humans and various species of
      animals. Here, a novel gemycircularvirus named Ch-zjrat-01 from blood samples of
      experimental rats was characterized. The novel gemycircularvirus encodes two
      major proteins, including a capsid protein (Cap) and a replication-associated
      protein (Rep). Phylogenetic analysis based on the amino acid sequence of Rep
      indicated that Ch-zjrat-01 clusters with two gemycircularviruses discovered from
      bird (KF371635) and mosquito (HQ335086), sharing 48.7 and 49.4 % sequence
      identities with them, respectively.

PMID- 26303899
TI  - Complete genome sequence analysis of enterovirus 71 isolated from children with
      hand, foot, and mouth disease in Thailand, 2012-2014.
AB  - The complete genomic sequences of 14 enterovirus 71 (EV71) strains isolated from
      children with hand, foot, and mouth disease in Thailand from 2012 to 2014 were
      determined and compared to enterovirus group A prototypes. Phylogenetic analysis
      revealed that 13 strains resembled the B5 subgroup, while one strain from a fatal
      case designated THA_1219 belonged to the C4 subgroup. Similarity plot and
      bootscan analyses suggested that THA_1219 underwent recombination in the P2 and
      P3 regions. Full-genome data from this work will contribute to the study of
      evolution dynamics of EV71.

PMID- 26303900
TI  - Employers' perceptions and attitudes toward the Canadian national standard on
      psychological health and safety in the workplace: A qualitative study.
AB  - The estimated societal and economic costs of mental illness and psychological
      injury in the workplace is staggering. Governments, employers and other
      stakeholders have been searching for policy solutions. This qualitative,
      exploratory study sought to uncover organizational receptivity to a voluntary
      comprehensive standard for dealing with psychological health and safety in the
      workplace. A series of five focus groups were conducted in a large Western
      Canadian city in November 2013. The seventeen participants were from the fields
      of healthcare, construction/utilities, manufacturing industries, business
      services, and finance. They worked in positions of management, consulting, human
      resources, health promotion, health and safety, mediation, and occupational
      health and represented organizations ranging in size from 20 to 100,000
      employees. The findings confirm and illustrate the critical role that
      psychological health and safety plays across workplaces and occupations. This
      standard resonated across the represented organizations and fit with their
      values. This alignment posed challenges with articulating its added value. There
      appears to be a need for simplified engagement and implementation strategies of
      the standard that can be tailored to the nuanced differences between types and
      sizes of industries. It appears that organizations in the most need of improving
      psychological health and safety may be the least receptive. 

PMID- 26303901
TI  - Validation of the Buss-Perry Aggression Questionnaire-Short Form among Portuguese
      juvenile delinquents.
AB  - The aim of the present study was to validate the Buss-Perry Aggression
      Questionnaire-Short Form (BPAQ-SF) among Portuguese juvenile delinquents. With a
      total sample of 237 male participants, subdivided into an incarcerated forensic
      sample (n=192) and a community sample (n=45), the Portuguese version of the BPAQ
      SF demonstrated good psychometric properties in terms of factor structure,
      internal consistency, convergent validity, discriminant validity, predictive
      validity and known-groups validity that generally justify its use among
      Portuguese youth. Statistically significant associations were found with drug use
      and alcohol abuse. 

PMID- 26303902
TI  - Linking Obesity Prevention and Mental Health Promotion to Address Health
      Disparities.
AB  - Considerable racial health disparities exist, especially in mental health and
      obesity. However, few approaches exist to address obesity and mental health
      simultaneously in minority groups. An intervention to address mental health in a
      low-income, minority group of urban mothers was designed using results from a
      needs assessment. Participating women were asked to rank their top health
      concerns and personal goals. Along with mental health concerns and basic needs,
      the majority of mothers desired assistance with improving their physical well
      being. These results are surprising, but lend credence to creating interventions
      that aim to address both mental health and obesity concerns simultaneously. 

PMID- 26303903
TI  - Risk Factors for Inpatient Psychiatric Readmission: Are There Gender Differences?
AB  - The objectives of the study were to compare characteristics of women and men
      discharged from an inpatient psychiatric facility and to identify gender-specific
      risk factors associated with 30-day and 1-year readmission using administrative
      data. The sample included adults discharged from an inpatient psychiatric
      facility in a Midwestern city (N = 1853). The analysis showed that the 30-day
      readmission rate was significantly lower among women, but there was no difference
      in the 1-year readmission rate. Risk factors for readmission differed by gender.
      For example, for 30-day readmission, being on Medicare versus commercial
      insurance increased the odds for women (OR 3.08; 95 % CI 1.35-7.04) and taking
      first-generation antipsychotics versus no antipsychotics increased the odds for
      men (OR 2.09; 95 % CI 1.26-3.48). These findings suggest there are important
      differences between women and men readmitted to an inpatient psychiatric
      facility. Future strategies need to take into account gender-specific risk
      factors in order to improve long-term patient outcomes.

PMID- 26303904
TI  - Burnout and Psychiatric Distress in Local Caregivers Two Years After the 2011
      Great East Japan Earthquake and Fukushima Nuclear Radiation Disaster.
AB  - The 2011 Great East Japan Earthquake precipitated a triple disaster of
      earthquake, tsunami and nuclear radiation disaster. To quantify the prevalence of
      burnout and psychiatric distress in local healthcare providers (caregivers) more
      than 2 years after the disaster, this study surveyed caregivers from affected
      areas through interviews about topics of concerns and two questionnaires: Maslach
      Burnout Inventory and General Health Questionnaire. Concerns listed by
      respondents were primarily radiation related: additional stress, concern for
      children, concern for local food, and sleep difficulties. We found significant
      number of caregivers to have signs of emotional exhaustion, low personal
      accomplishment, and psychological distress. Our findings suggest that local
      caregivers are experiencing substantial mental health burdens, which have
      unfortunately remained static from the year prior, even 2 years after the fact.
      Therefore, long term psychological support and improvement in caregiver work
      conditions are essential to maintain sustainable care in rebuilding disaster
      stricken areas. 

PMID- 26303905
TI  - Mental Health Care Providers' Views of Their Work with Consumers and Their
      Reports of Recovery-Orientation, Job Satisfaction, and Personal Growth.
AB  - The research examined the role of mental health care providers' perceptions of
      their professional relationships with consumers in understanding their reports of
      agency recovery-oriented services and their own sense of job satisfaction and
      personal growth. Multidisciplinary community mental health care providers (N =
      105) responded to an online self-report questionnaire. Providers' reports of
      higher levels of working alliance and greater provider directiveness in working
      with consumers was significantly related to providers' reports of higher levels
      of agency recovery-orientation and higher levels of personal growth. Providers'
      reports of working alliance accounted for the largest proportion of variance in
      providers' reports of job satisfaction. Mental health providers' perceptions of
      relationships with consumers are central to understanding providers' views of
      agency recovery-orientation and sense of professional and personal well-being.

PMID- 26303907
TI  - Erratum to: ComOn Coaching: study protocol of a randomized controlled trial to
      assess the effect of a varied number of coaching sessions on transfer into
      clinical practice following communication skills training.

PMID- 26303908
TI  - Lentisphaera profundi sp. nov., isolated from deep-sea water.
AB  - A Gram-staining-negative, aerobic, non-motile, coccus-shaped bacterium,
      designated SAORIC-696T, was isolated from deep-sea water at a depth of 1700 m in
      the western North Pacific Ocean. Optimal growth of strain SAORIC-696T was
      observed at 15  degrees C, pH 7.0 and in the presence of 2 % (w/v) NaCl. Strain
      SAORIC-696T formed a robust phylogenetic clade with members of the genus
      Lentisphaera. The 16S rRNA gene sequence similarity showed that strain SAORIC
      696T was most closely related to Lentisphaera marina (98.0 % similarity) and
      Lentisphaera araneosa (97.3 %). The DNA-DNA relatedness between SAORIC-696T and
      two species of the genus Lentisphaera was only 27-42 %. The DNA G+C content of
      strain SAORIC-696T was 43.1 mol% and predominant cellular fatty acids were C16 :
      1omega9c (36.8 %), C14 : 0 (22.5 %) and C14 : 0 3-OH and/or iso-C16 : 1 I (10.8
      %). Strain SAORIC-696T contained MK-7 as the only respiratory quinone. On the
      basis of taxonomic data collected in this study, it was concluded that strain
      SAORIC-696T represents a novel species of the genus Lentisphaera, for which the
      name Lentisphaera profundi sp. nov. is proposed, with the type strain SAORIC-696T
      ( = NBRC 110692T = KCTC 42681T).

PMID- 26303906
TI  - RuvbL1 and RuvbL2 enhance aggresome formation and disaggregate amyloid fibrils.
AB  - The aggresome is an organelle that recruits aggregated proteins for storage and
      degradation. We performed an siRNA screen for proteins involved in aggresome
      formation and identified novel mammalian AAA+ protein disaggregases RuvbL1 and
      RuvbL2. Depletion of RuvbL1 or RuvbL2 suppressed aggresome formation and caused
      buildup of multiple cytoplasmic aggregates. Similarly, downregulation of RuvbL
      orthologs in yeast suppressed the formation of an aggresome-like body and
      enhanced the aggregate toxicity. In contrast, their overproduction enhanced the
      resistance to proteotoxic stress independently of chaperone Hsp104. Mammalian
      RuvbL associated with the aggresome, and the aggresome substrate synphilin-1
      interacted directly with the RuvbL1 barrel-like structure near the opening of the
      central channel. Importantly, polypeptides with unfolded structures and amyloid
      fibrils stimulated the ATPase activity of RuvbL. Finally, disassembly of protein
      aggregates was promoted by RuvbL. These data indicate that RuvbL complexes serve
      as chaperones in protein disaggregation. 

PMID- 26303909
TI  - Equally able, but unequally accepted: Gender differentials and experiences of
      community health volunteers promoting maternal, newborn, and child health in
      Morogoro Region, Tanzania.
AB  - BACKGROUND: Despite emerging qualitative evidence of gendered community health
      worker (CHW) experience, few quantitative studies examine CHW gender
      differentials. The launch of a maternal, newborn, and child health (MNCH) CHW
      cadre in Morogoro Region, Tanzania enlisting both males and females as CHWs,
      provides an opportunity to examine potential gender differences in CHW knowledge,
      health promotion activities and client acceptability. METHODS: All CHWs who
      received training from the Integrated MNCH Program between December 2012 and July
      2013 in five districts were surveyed and information on health promotion
      activities undertaken drawn from their registers. CHW socio-demographic
      characteristics, knowledge, and health promotion activities were analyzed through
      bi- and multivariate analyses. Composite scores generated across ten knowledge
      domains were used in ordered logistic regression models to estimate relationships
      between knowledge scores and predictor variables. Thematic analysis was also
      undertaken on 60 purposively sampled semi-structured interviews with CHWs, their
      supervisors, community leaders, and health committee members in 12 villages from
      three districts. RESULTS: Of all CHWs trained, 97% were interviewed (n = 228):
      55% male and 45% female. No significant differences were observed in knowledge by
      gender after controlling for age, education, date of training, marital status,
      and assets. Differences in number of home visits and community health education
      meetings were also not significant by gender. With regards to acceptability,
      women were more likely to disclose pregnancies earlier to female CHWs, than male
      CHWs. Men were more comfortable discussing sexual and reproductive concerns with
      male, than female CHWs. In some cases, CHW home visits were viewed as potentially
      being for ulterior or adulterous motives, so trust by families had to be built.
      Respondents reported that working as female-male pairs helped to address some of
      these dynamics. CONCLUSIONS: Male and female CHWs in this study have largely
      similar knowledge and health promotion outputs, but challenges in acceptance of
      CHW counseling for reproductive health and home visits by unaccompanied CHWs
      varied by gender. Programs that pair male and female CHWs may potentially
      overcome gender issues in CHW acceptance, especially if they change gender norms
      rather than solely accommodate gender preferences.

PMID- 26303910
TI  - TRPV1 channel inhibition contributes to the antinociceptive effects of Croton
      macrostachyus extract in mice.
AB  - BACKGROUND: Previous study showed that extracts from Croton macrostachyus
      (Euphorbiaceae) exhibit analgesic effects in acute pain models. The present study
      evaluates the antinociceptive properties of the methanol/methylene chloride
      extract (MECM) of the stem bark of this plant using mice models of persistent
      inflammatory and neuropathic pain, and assesses its mechanism of action. METHODS:
      MECM was tested on Complete Freund adjuvant (CFA)-induced persistent thermal and
      mechanical pain, neuropathic pain induced by partial sciatic nerve ligation
      (PSNL), prostaglandin E2 (PGE2)-induced acute mechanical hyperalgesia, as well as
      on nociception induced by capsaicin in mice. Mechanical hyperalgesia was assessed
      using von Frey hair in awake mice. The mechanism of action of MECM was evaluated
      by using glibenclamide on PGE2-induced hyperalgesia or rimonabant on capsaicin
      induced pain. RESULTS: MECM administered orally at the doses of 250 and 500
      mg/kg, induced long lasting and significant antihyperalgesic effects on CFA
      inflammatory and PSNL-induced neuropathic pain. MECM significantly reduced the
      mechanical hyperalgesia induced by PGE2 either when administered preventively or
      therapeutically. MECM also significantly and time dependently inhibited the
      capsaicin-induced nociception. These effects were not affected by glibenclamide
      or by rimonabant. CONCLUSIONS: The present results demonstrate that the oral
      administration of MECM to mice resulted in long lasting antihyperalgesic activity
      in inflammatory and neuropathic pain as well as in acute and persistent pain. The
      mechanism underlying the long lasting MECM antihyperalgesic effect is currently
      unknown, but might be mediated, at least partially, through the modulation of
      TRPV1 receptors.

PMID- 26303913
TI  - Marinibacterium profundimaris gen. nov., sp. nov., isolated from deep seawater.
AB  - A taxonomic study was carried out on strain 22II1-22F33T, which was isolated from
      deep seawater of the Atlantic Ocean. The bacterium was Gram-stain-negative,
      oxidase-positive and weakly catalase-positive, oval in shape without flagellum.
      Growth was observed at salinities of 0-12 % and at temperatures of 4-41  degrees
      C. The isolate was capable of hydrolysing aesculin and Tween 80 and reduction of
      nitrate to nitrite, but unable to hydrolyse gelatin. Phylogenetic analysis based
      on 16S rRNA gene sequences indicated that strain 22II1-22F33T belongs to the
      family Rhodobacteraceae, with highest sequence similarity to Pseudooceanicola
      marinus AZO-CT (96.5 %). The principal fatty acids (>10 %) were summed feature 8
      (C18 : 1omega7c/omega6c) (73.8 %). The G+C content of the genomic DNA was 66.2
      mol%. The respiratory quinone was Q-10 (100 %). Phosphatidylethanolamine (PE),
      phosphatidylglycerol (PG), phosphatidylcholine (PC), two unidentified aminolipids
      (ALs), six unidentified phospholipids (PLs) and one unidentified lipid (L) were
      present. The combined genotypic and phenotypic data show that strain 22II1-22F33T
      represents a novel species within a new genus, for which the name Marinibacterium
      profundimaris gen. nov., sp. nov. is proposed. The type strain of Marinibacterium
      profundimaris is 22II1-22F33T ( = LMG 27151T = MCCC 1A09326T).

PMID- 26303911
TI  - Identification of microRNAs associated with allergic airway disease using a
      genetically diverse mouse population.
AB  - BACKGROUND: Allergic airway diseases (AADs) such as asthma are characterized in
      part by granulocytic airway inflammation. The gene regulatory networks that
      govern granulocyte recruitment are poorly understood, but evidence is accruing
      that microRNAs (miRNAs) play an important role. To identify miRNAs that may
      underlie AADs, we used two complementary approaches that leveraged the genotypic
      and phenotypic diversity of the Collaborative Cross (CC) mouse population. In the
      first approach, we sought to identify miRNA expression quantitative trait loci
      (eQTL) that overlap QTL for AAD-related phenotypes. Specifically, CC founder
      strains and incipient lines of the CC were sensitized and challenged with house
      dust mite allergen followed by measurement of granulocyte recruitment to the
      lung. Total lung RNA was isolated and miRNA was measured using arrays for CC
      founders and qRT-PCR for incipient CC lines. RESULTS: Among CC founders, 92
      miRNAs were differentially expressed. We measured the expression of 40 of the
      most highly expressed of these 92 miRNAs in the incipient lines of the CC and
      identified 18 eQTL corresponding to 14 different miRNAs. Surprisingly, half of
      these eQTL were distal to the corresponding miRNAs, and even on different
      chromosomes. One of the largest-effect local miRNA eQTL was for miR-342-3p, for
      which we identified putative causal variants by bioinformatic analysis of the
      effects of single nucleotide polymorphisms on RNA structure. None of the miRNA
      eQTL co-localized with QTL for eosinophil or neutrophil recruitment. In the
      second approach, we constructed putative miRNA/mRNA regulatory networks and
      identified three miRNAs (miR-497, miR-351 and miR-31) as candidate master
      regulators of genes associated with neutrophil recruitment. Analysis of a dataset
      from human keratinocytes transfected with a miR-31 inhibitor revealed two target
      genes in common with miR-31 targets correlated with neutrophils, namely Oxsr1 and
      Nsf. CONCLUSIONS: miRNA expression in the allergically inflamed murine lung is
      regulated by genetic loci that are smaller in effect size compared to mRNA eQTL
      and often act in trans. Thus our results indicate that the genetic architecture
      of miRNA expression is different from mRNA expression. We identified three
      miRNAs, miR-497, miR-351 and miR-31, that are candidate master regulators of
      genes associated with neutrophil recruitment. Because miR-31 is expressed in
      airway epithelia and is predicted to target genes with known links to
      neutrophilic inflammation, we suggest that miR-31 is a potentially novel
      regulator of airway inflammation.

PMID- 26303912
TI  - Mindfulness-based cognitive therapy for inflammatory bowel disease patients:
      findings from an exploratory pilot randomised controlled trial.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is a chronic gastrointestinal
      condition with a relapsing disease course. Managing the relapsing nature of the
      disease causes daily stress for IBD patients; thus, IBD patients report higher
      rates of depression and anxiety than the general population. Mindfulness-based
      Cognitive Therapy (MBCT) is an evidence-based psychological program designed to
      help manage depressive and stress symptoms. There has been no randomized
      controlled trial (RCT) testing the use of MBCT in IBD patients. The purpose of
      this pilot study is to test the trial methodology and assess the feasibility of
      conducting a large RCT testing the effectiveness of MBCT in IBD. METHODS: The IBD
      patients, who were recruited from gastroenterology outpatient clinics at two
      Scottish NHS Boards, were randomly allocated to an MBCT intervention group (n =
      22) or a wait-list control group (n = 22). The MBCT intervention consisted of 16
      hours of structured group training over 8 consecutive weeks plus guided home
      practice and follow-up sessions. The wait-list group received a leaflet entitled
      'Staying well with IBD'. All participants completed a baseline, post-intervention
      and 6-month follow up assessment. The key objectives were to assess patient
      eligibility and recruitment/dropout rate, to calculate initial estimates of
      parameters to the proposed outcome measures (depression, anxiety, disease
      activity, dispositional mindfulness and quality of life) and to estimate sample
      size for a future large RCT. RESULTS: In total, 350 patients were assessed for
      eligibility. Of these, 44 eligible patients consented to participate. The
      recruitment rate was 15%, with main reasons for ineligibility indicated as
      follows: non-response to invitation, active disease symptoms, planned surgery or
      incompatibility with group schedule. There was a higher than expected dropout
      rate of 44%. Initial estimates of parameters to the proposed outcomes at post
      intervention and follow-up showed a significant improvement of scores in the MBCT
      group when compared to the control for depression, trait anxiety and
      dispositional mindfulness. The sample-size calculation was guided by estimates of
      clinically important effects in depression scores. CONCLUSIONS: This pilot study
      suggests that a multicentre randomized clinical trial testing the effectiveness
      of MBCT for IBD patients is feasible with some changes to the protocol.
      Improvement in depression, trait anxiety and dispositional mindfulness scores are
      promising when coupled with patients reporting a perceived improvement of their
      quality of life. TRIAL REGISTRATION: ISRCTN27934462. 2 August 2013.

PMID- 26303915
TI  - Numerical continuation and bifurcation analysis in aircraft design: an industrial
      perspective.
AB  - Bifurcation analysis is a powerful method for studying the steady-state nonlinear
      dynamics of systems. Software tools exist for the numerical continuation of
      steady-state solutions as parameters of the system are varied. These tools make
      it possible to generate 'maps of solutions' in an efficient way that provide
      valuable insight into the overall dynamic behaviour of a system and potentially
      to influence the design process. While this approach has been employed in the
      military aircraft control community to understand the effectiveness of
      controllers, the use of bifurcation analysis in the wider aircraft industry is
      yet limited. This paper reports progress on how bifurcation analysis can play a
      role as part of the design process for passenger aircraft. 

PMID- 26303914
TI  - Social determinants of health inequalities: towards a theoretical perspective
      using systems science.
AB  - A systems approach offers a novel conceptualization to natural and social
      systems. In recent years, this has led to perceiving population health outcomes
      as an emergent property of a dynamic and open, complex adaptive system. The
      current paper explores these themes further and applies the principles of systems
      approach and complexity science (i.e. systems science) to conceptualize social
      determinants of health inequalities. The conceptualization can be done in two
      steps: viewing health inequalities from a systems approach and extending it to
      include complexity science. Systems approach views health inequalities as
      patterns within the larger rubric of other facets of the human condition, such as
      educational outcomes and economic development. This anlysis requires more
      sophisticated models such as systems dynamic models. An extension of the approach
      is to view systems as complex adaptive systems, i.e. systems that are 'open' and
      adapt to the environment. They consist of dynamic adapting subsystems that
      exhibit non-linear interactions, while being 'open' to a similarly dynamic
      environment of interconnected systems. They exhibit emergent properties that
      cannot be estimated with precision by using the known interactions among its
      components (such as economic development, political freedom, health system,
      culture etc.). Different combinations of the same bundle of factors or
      determinants give rise to similar patterns or outcomes (i.e. property of
      convergence), and minor variations in the initial condition could give rise to
      widely divergent outcomes. Novel approaches using computer simulation models
      (e.g. agent-based models) would shed light on possible mechanisms as to how
      factors or determinants interact and lead to emergent patterns of health
      inequalities of populations. 

PMID- 26303916
TI  - Bayesian and Markov chain Monte Carlo methods for identifying nonlinear systems
      in the presence of uncertainty.
AB  - In this paper, the authors outline the general principles behind an approach to
      Bayesian system identification and highlight the benefits of adopting a Bayesian
      framework when attempting to identify models of nonlinear dynamical systems in
      the presence of uncertainty. It is then described how, through a summary of some
      key algorithms, many of the potential difficulties associated with a Bayesian
      approach can be overcome through the use of Markov chain Monte Carlo (MCMC)
      methods. The paper concludes with a case study, where an MCMC algorithm is used
      to facilitate the Bayesian system identification of a nonlinear dynamical system
      from experimentally observed acceleration time histories. 

PMID- 26303917
TI  - The use of normal forms for analysing nonlinear mechanical vibrations.
AB  - A historical introduction is given of the theory of normal forms for simplifying
      nonlinear dynamical systems close to resonances or bifurcation points. The
      specific focus is on mechanical vibration problems, described by finite degree-of
      freedom second-order-in-time differential equations. A recent variant of the
      normal form method, that respects the specific structure of such models, is
      recalled. It is shown how this method can be placed within the context of the
      general theory of normal forms provided the damping and forcing terms are treated
      as unfolding parameters. The approach is contrasted to the alternative theory of
      nonlinear normal modes (NNMs) which is argued to be problematic in the presence
      of damping. The efficacy of the normal form method is illustrated on a model of
      the vibration of a taut cable, which is geometrically nonlinear. It is shown how
      the method is able to accurately predict NNM shapes and their bifurcations. 

PMID- 26303918
TI  - On the bistable zone of milling processes.
AB  - A modal-based model of milling machine tools subjected to time-periodic nonlinear
      cutting forces is introduced. The model describes the phenomenon of bistability
      for certain cutting parameters. In engineering, these parameter domains are
      referred to as unsafe zones, where steady-state milling may switch to chatter for
      certain perturbations. In mathematical terms, these are the parameter domains
      where the periodic solution of the corresponding nonlinear, time-periodic delay
      differential equation is linearly stable, but its domain of attraction is limited
      due to the existence of an unstable quasi-periodic solution emerging from a
      secondary Hopf bifurcation. A semi-numerical method is presented to identify the
      borders of these bistable zones by tracking the motion of the milling tool edges
      as they might leave the surface of the workpiece during the cutting operation.
      This requires the tracking of unstable quasi-periodic solutions and the checking
      of their grazing to a time-periodic switching surface in the infinite-dimensional
      phase space. As the parameters of the linear structural behaviour of the
      tool/machine tool system can be obtained by means of standard modal testing, the
      developed numerical algorithm provides efficient support for the design of
      milling processes with quick estimates of those parameter domains where chatter
      can still appear in spite of setting the parameters into linearly stable domains.

PMID- 26303919
TI  - On the nonlinear dynamics of a rotor in autorotation: a combined experimental and
      numerical approach.
AB  - This article presents a systematic assessment of the use of numerical
      continuation and bifurcation techniques in investigating the nonlinear periodic
      behaviour of a teetering rotor operating in forward autorotation. The aim is to
      illustrate the potential of these tools in revealing complex blade dynamics, when
      used in combination (not necessarily at the same time) with physical testing. We
      show a simple procedure to promote understanding of an existing but not fully
      understood engineering instability problem, when uncertainties in the numerical
      modelling and constraints in the experimental testing are present. It is proposed
      that continuation and bifurcation methods can play a significant role in
      developing numerical and experimental techniques for studying the nonlinear
      dynamics not only for rotating blades but also for other engineering systems with
      uncertainties and constraints. 

PMID- 26303920
TI  - Are there reliable constitutive laws for dynamic friction?
AB  - Structural vibration controlled by interfacial friction is widespread, ranging
      from friction dampers in gas turbines to the motion of violin strings. To
      predict, control or prevent such vibration, a constitutive description of
      frictional interactions is inevitably required. A variety of friction models are
      discussed to assess their scope and validity, in the light of constraints
      provided by different experimental observations. Three contrasting case studies
      are used to illustrate how predicted behaviour can be extremely sensitive to the
      choice of frictional constitutive model, and to explore possible experimental
      paths to discriminate between and calibrate dynamic friction models over the full
      parameter range needed for real applications. 

PMID- 26303921
TI  - Nonlinear damping and quasi-linear modelling.
AB  - The mechanism of energy dissipation in mechanical systems is often nonlinear.
      Even though there may be other forms of nonlinearity in the dynamics, nonlinear
      damping is the dominant source of nonlinearity in a number of practical systems.
      The analysis of such systems is simplified by the fact that they show no jump or
      bifurcation behaviour, and indeed can often be well represented by an equivalent
      linear system, whose damping parameters depend on the form and amplitude of the
      excitation, in a 'quasi-linear' model. The diverse sources of nonlinear damping
      are first reviewed in this paper, before some example systems are analysed,
      initially for sinusoidal and then for random excitation. For simplicity, it is
      assumed that the system is stable and that the nonlinear damping force depends on
      the nth power of the velocity. For sinusoidal excitation, it is shown that the
      response is often also almost sinusoidal, and methods for calculating the
      amplitude are described based on the harmonic balance method, which is closely
      related to the describing function method used in control engineering. For random
      excitation, several methods of analysis are shown to be equivalent. In general,
      iterative methods need to be used to calculate the equivalent linear damper,
      since its value depends on the system's response, which itself depends on the
      value of the equivalent linear damper. The power dissipation of the equivalent
      linear damper, for both sinusoidal and random cases, matches that dissipated by
      the nonlinear damper, providing both a firm theoretical basis for this modelling
      approach and clear physical insight. Finally, practical examples of nonlinear
      damping are discussed: in microspeakers, vibration isolation, energy harvesting
      and the mechanical response of the cochlea. 

PMID- 26303922
TI  - Structural optimization for nonlinear dynamic response.
AB  - Much is known about the nonlinear resonant response of mechanical systems, but
      methods for the systematic design of structures that optimize aspects of these
      responses have received little attention. Progress in this area is particularly
      important in the area of micro-systems, where nonlinear resonant behaviour is
      being used for a variety of applications in sensing and signal conditioning. In
      this work, we describe a computational method that provides a systematic means
      for manipulating and optimizing features of nonlinear resonant responses of
      mechanical structures that are described by a single vibrating mode, or by a pair
      of internally resonant modes. The approach combines techniques from nonlinear
      dynamics, computational mechanics and optimization, and it allows one to relate
      the geometric and material properties of structural elements to terms in the
      normal form for a given resonance condition, thereby providing a means for
      tailoring its nonlinear response. The method is applied to the fundamental
      nonlinear resonance of a clamped-clamped beam and to the coupled mode response of
      a frame structure, and the results show that one can modify essential normal form
      coefficients by an order of magnitude by relatively simple changes in the shape
      of these elements. We expect the proposed approach, and its extensions, to be
      useful for the design of systems used for fundamental studies of nonlinear
      behaviour as well as for the development of commercial devices that exploit
      nonlinear behaviour. 

PMID- 26303923
TI  - Statistical energy analysis of nonlinear vibrating systems.
AB  - Nonlinearities in practical systems can arise in contacts between components,
      possibly from friction or impacts. However, it is also known that quadratic and
      cubic nonlinearity can occur in the stiffness of structural elements undergoing
      large amplitude vibration, without the need for local contacts. Nonlinearity due
      purely to large amplitude vibration can then result in significant energy being
      found in frequency bands other than those being driven by external forces. To
      analyse this phenomenon, a method is developed here in which the response of the
      structure in the frequency domain is divided into frequency bands, and the energy
      flow between the frequency bands is calculated. The frequency bands are assigned
      an energy variable to describe the mean response and the nonlinear coupling
      between bands is described in terms of weighted summations of the convolutions of
      linear modal transfer functions. This represents a nonlinear extension to an
      established linear theory known as statistical energy analysis (SEA). The
      nonlinear extension to SEA theory is presented for the case of a plate structure
      with quadratic and cubic nonlinearity. 

PMID- 26303924
TI  - Modal testing for model validation of structures with discrete nonlinearities.
AB  - Model validation using data from modal tests is now widely practiced in many
      industries for advanced structural dynamic design analysis, especially where
      structural integrity is a primary requirement. These industries tend to demand
      highly efficient designs for their critical structures which, as a result, are
      increasingly operating in regimes where traditional linearity assumptions are no
      longer adequate. In particular, many modern structures are found to contain
      localized areas, often around joints or boundaries, where the actual mechanical
      behaviour is far from linear. Such structures need to have appropriate
      representation of these nonlinear features incorporated into the otherwise
      largely linear models that are used for design and operation. This paper proposes
      an approach to this task which is an extension of existing linear techniques,
      especially in the testing phase, involving only just as much nonlinear analysis
      as is necessary to construct a model which is good enough, or 'valid': i.e.
      capable of predicting the nonlinear response behaviour of the structure under all
      in-service operating and test conditions with a prescribed accuracy. A short-list
      of methods described in the recent literature categorized using our framework is
      given, which identifies those areas in which further development is most urgently
      required. 

PMID- 26303925
TI  - The landscape of nonlinear structural dynamics: an introduction.
AB  - Nonlinear behaviour is ever-present in vibrations and other dynamical motions of
      engineering structures. Manifestations of nonlinearity include amplitude
      dependent natural frequencies, buzz, squeak and rattle, self-excited oscillation
      and non-repeatability. This article primarily serves as an extended introduction
      to a theme issue in which such nonlinear phenomena are highlighted through
      diverse case studies. More ambitiously though, there is another goal. Both the
      engineering context and the mathematical techniques that can be used to identify,
      analyse, control or exploit these phenomena in practice are placed in the context
      of a mind-map, which has been created through expert elicitation. This map, which
      is available in software through the electronic supplementary material, attempts
      to provide a practitioner's guide to what hitherto might seem like a vast and
      complex research landscape. 

PMID- 26303926
TI  - Critical care nursing organizations and activities: a fourth worldwide review.
AB  - AIM: To examine the activities and concerns of critical care nurses and
      professional critical care nursing organizations around the world and to identify
      expectations held of nursing leaders and policy makers to help address their
      concerns. BACKGROUND: This study is the fourth worldwide review of its type.
      Previous surveys were undertaken in 2001, 2005 and 2009. METHODS: An online
      descriptive survey was emailed to 88 potential participants from countries with
      critical care nursing organizations or known critical care nursing leaders.
      Responses were downloaded into Survey MonkeyTM (Version 22) and analysed by
      geographical region and income level. RESULTS: Fifty-nine respondents from 58
      countries completed the questionnaire, of whom 43 had critical care nursing
      organizations established in their countries and 29 were members of the World
      Federation of Critical Care Nurses. The services provided by the organizations to
      be of most value were national conferences, website, professional representation,
      and practice standards and guidelines. Professional policies had been developed
      by some organizations on workforce, education and practice, while almost half
      provided their members with either a newsletter or journal. Collectively, the
      most important issues for critical care nurses were working conditions, provision
      of formal practice guidelines and competencies, staffing levels and access to
      quality education programmes. CONCLUSIONS: Important issues continue to challenge
      the specialty of critical care nursing as new developments, priorities, clinical
      issues and other global events and influences impact critical care nursing
      worldwide. IMPLICATIONS FOR NURSING AND HEALTH POLICY: This study will help guide
      nursing leaders and policy makers to address the needs of critical care nurses
      and their patients. Collaborative approaches between the specialty, nursing
      leaders and health policy advisors will assist to inform appropriate change in
      areas recommended for further action.

PMID- 26303927
TI  - Chagas disease reactivation in a heart transplant patient infected by domestic
      Trypanosoma cruzi discrete typing unit I (TcIDOM).
AB  - BACKGROUND: Trypanosoma cruzi, causative agent of Chagas disease, displays high
      intraspecific genetic diversity: six genetic lineages or discrete typing units
      (DTUs) are currently recognized, termed TcI through TcVI. Each DTU presents a
      particular distribution pattern across the Americas, and is loosely associated
      with different transmission cycles and hosts. Several DTUs are known to circulate
      in Central America. It has been previously suggested that TcI infection is benign
      and does not lead to chronic chagasic cardiomyopathy (CCC). FINDINGS: In this
      study, we genotyped T. cruzi parasites circulating in the blood and from
      explanted cardiac tissue of an El Salvadorian patient who developed reactivation
      Chagas disease while on immunosuppressive medications after undergoing heart
      transplant in the U.S. as treatment for end-stage CCC. Parasite typing was
      performed through molecular methods (restriction fragment length polymorphism of
      polymerase reaction chain amplified products, microsatellite typing, maxicircle
      sequence typing and low-stringency single primer PCR, [LSSP-PCR]) as well as
      lineage-specific serology. We show that the parasites infecting the patient
      belong to the TcI DTU exclusively. Our data indicate that the parasites isolated
      from the patient belong to a genotype frequently associated with human infection
      throughout the Americas (TcIDOM). CONCLUSIONS: Our results constitute compelling
      evidence in support of TcI DTU's ability to cause end-stage CCC and help dispel
      any residual bias that infection with this lineage is benign, pointing to the
      need for increased surveillance for dissemination of this genotype in endemic
      regions, the USA and globally.

PMID- 26303928
TI  - Intraocular myofibroblastoma in an infant: a case report.
AB  - BACKGROUND: Myofibroblastoma is a benign tumor composed of spindle cells and
      bands of hyalinized collagen. Intraocular myofibroblastoma in infancy is rarely
      encountered. CASE PRESENTATION: The present study reports the case of a 4-month
      old female baby with intraocular myofibroblastoma. She was suspected as corneal
      perforation due to the rupture of a corneal neoplasm in the right eye. The
      anterior segment was also involved according to the Color Doppler
      ultrasonography. A surgical exploration was performed and the protuberant part of
      the mass was resected. Conventional HE staining showed numerous spindle-shaped
      cells with bands of collagen beneath multilayers of well-differentiated corneal
      epithelia. Immunohistochemical staining demonstrated the tumor cells were strong
      positive for vimentin and smooth muscle actin, while negative for S-100 protein.
      The mass was confirmed as myofibroblastoma. After 12 month follow-up, there was
      no apparent growth of the tumor. CONCLUSIONS: Myofibroblastoma is a very rare
      type of intraocular neoplasm, which may have complicated manifestation and could
      be misdiagnosed as dermoid or Peter's anomaly. Histopathological and
      immunohistochemical staining is crucial to form a precise diagnosis.

PMID- 26303929
TI  - Improving activity recognition using a wearable barometric pressure sensor in
      mobility-impaired stroke patients.
AB  - BACKGROUND: Stroke survivors often suffer from mobility deficits. Current
      clinical evaluation methods, including questionnaires and motor function tests,
      cannot provide an objective measure of the patients' mobility in daily life.
      Physical activity performance in daily-life can be assessed using unobtrusive
      monitoring, for example with a single sensor module fixed on the trunk. Existing
      approaches based on inertial sensors have limited performance, particularly in
      detecting transitions between different activities and postures, due to the
      inherent inter-patient variability of kinematic patterns. To overcome these
      limitations, one possibility is to use additional information from a barometric
      pressure (BP) sensor. METHODS: Our study aims at integrating BP and inertial
      sensor data into an activity classifier in order to improve the activity
      (sitting, standing, walking, lying) recognition and the corresponding body
      elevation (during climbing stairs or when taking an elevator). Taking into
      account the trunk elevation changes during postural transitions (sit-to-stand,
      stand-to-sit), we devised an event-driven activity classifier based on fuzzy
      logic. Data were acquired from 12 stroke patients with impaired mobility, using a
      trunk-worn inertial and BP sensor. Events, including walking and lying periods
      and potential postural transitions, were first extracted. These events were then
      fed into a double-stage hierarchical Fuzzy Inference System (H-FIS). The first
      stage processed the events to infer activities and the second stage improved
      activity recognition by applying behavioral constraints. Finally, the body
      elevation was estimated using a pattern-enhancing algorithm applied on BP. The
      patients were videotaped for reference. The performance of the algorithm was
      estimated using the Correct Classification Rate (CCR) and F-score. The BP-based
      classification approach was benchmarked against a previously-published fuzzy
      logic classifier (FIS-IMU) and a conventional epoch-based classifier (EPOCH).
      RESULTS: The algorithm performance for posture/activity detection, in terms of
      CCR was 90.4 %, with 3.3 % and 5.6 % improvements against FIS-IMU and EPOCH,
      respectively. The proposed classifier essentially benefits from a better
      recognition of standing activity (70.3 % versus 61.5 % [FIS-IMU] and 42.5 %
      [EPOCH]) with 98.2 % CCR for body elevation estimation. CONCLUSION: The
      monitoring and recognition of daily activities in mobility-impaired stoke
      patients can be significantly improved using a trunk-fixed sensor that integrates
      BP, inertial sensors, and an event-based activity classifier.

PMID- 26303930
TI  - A cross-sectional study of pedagogical strategies in nursing education:
      opportunities and constraints toward using effective pedagogy.
AB  - BACKGROUND: The continuous, rapid evolution of medical technology, the public
      need for ever more complex health-care services and the stagnant global economic
      situation have posed difficult new challenges for the nursing profession. The
      need to integrate knowledge, technical skill and ethical conduct in nursing
      practice has become ever more evident, particularly in response to the emerging
      challenges over recent years. Major research studies have highlighted that high
      quality responses to health needs is highly dependent on both the education
      received by health care professionals and the pedagogical strategies employed in
      such training. The aim of this study was to identify the pedagogical strategies
      used by teachers in nursing programs in the Italian university system and to
      classify them according to the didactic architectures that are used. METHODS: The
      study sample was recruited from the entire population of nursing instructors
      teaching in all years of their respective programs, in every Italian university
      with a nursing program. A three-part questionnaire, based on a Calvani taxonomy,
      was designed to collect both demographic and cultural information on the sample
      subjects, as well as the pedagogical strategies that they may have used in their
      teaching practices, was administered to all nursing instructors. A five-point
      Likert scale was used to measure the frequency of use of different pedagogical
      strategies. RESULTS: On the whole, 992 teachers participated in the study (80.1%
      of the teachers contacted). Experience data suggest a highly-educated overall
      instructor population. The settings in which the participants carried out their
      teaching activities were represented mostly by large lecture halls and the number
      of students in their classes were for the most part rather large; over 60.
      Frequency of use revealed that the most commonly used method was the traditional
      lecture. Indeed, 85.7% of the respondents "often" or "always" used pedagogical
      strategies belonging to a 'receptive architecture'. CONCLUSIONS: Any redefining
      of approaches to nursing education must consider several key factors to ensure
      the promotion of student-focused pedagogical strategies. Only through the
      implementation of such pedagogical practices will it be possible to generate the
      knowledge and skills necessary for future professionals to be able to adequately
      respond to the ever more complex health care needs of the population.

PMID- 26303931
TI  - Where's the risk? Landscape epidemiology of gastrointestinal parasitism in
      Alberta beef cattle.
AB  - BACKGROUND: Gastrointenstinal nematodes (GIN) present a serious challenge to the
      health and productivity of grazing stock around the globe. However, the
      epidemiology of GIN transmission remains poorly understood in northern climates.
      Combining use of serological diagnostics, GIS mapping technology, and geospatial
      statistics, we evaluated ecological covariates of spatial and temporal
      variability in GIN transmission among bovine calves pastured in Alberta, Canada.
      METHODS: Sera were collected from 1000 beef calves across Alberta, Canada over
      three consecutive years (2008-2010) and analyzed for presence of anti-GIN
      antibodies using the SVANOVIR Ostertagia osteragi-Ab ELISA kit. Using a GIS and
      Bayesian multivariate spatial statistics, we evaluated the degree to which
      variation in specific environmental covariates (e.g. moisture, humidity,
      temperature) was associated with variation in spatial and temporal heterogeneity
      in exposure to GIN (Nematodirus and other trichostrongyles, primarily Ostertagia
      and Cooperia). RESULTS: Variation in growing degree days above a base temperature
      of 5  degrees C, humidity, air temperature, and accumulated precipitation were
      found to be significant predictors of broad-scale spatial and temporal variation
      in serum antibody concentrations. Risk model projections identified that while
      transmission in cattle from southeastern and northwestern Alberta was relatively
      low in all years, rate of GIN transmission was generally higher in the central
      region of Alberta. CONCLUSIONS: The spatial variability in risk is attributed to
      higher average humidity, precipitation and moderate temperatures in the central
      region of Alberta in comparison with the hot, dry southeastern corner of the
      province and the cool, dry northwestern corner. Although more targeted sampling
      is needed to improve model accuracy, our projections represent an important step
      towards tying treatment recommendations to actual risk of infection.

PMID- 26303932
TI  - Bifidobacteria grown on human milk oligosaccharides downregulate the expression
      of inflammation-related genes in Caco-2 cells.
AB  - BACKGROUND: Breastfed human infants are predominantly colonized by bifidobacteria
      that thrive on human milk oligosaccharides (HMO). Two predominant species of
      bifidobacteria in infant feces are Bifidobacterium breve (B. breve) and
      Bifidobacterium longum subsp. infantis (B. infantis), both of which include avid
      HMO-consumer strains. Our laboratory has previously shown that B. infantis, when
      grown on HMO, increases adhesion to intestinal cells and increases the expression
      of the anti-inflammatory cytokine interleukin-10. The purpose of the current
      study was to investigate the effects of carbon source-glucose, lactose, or HMO-on
      the ability of B. breve and B. infantis to adhere to and affect the transcription
      of intestinal epithelial cells on a genome-wide basis. RESULTS: HMO-grown B.
      infantis had higher percent binding to Caco-2 cell monolayers compared to B.
      infantis grown on glucose or lactose. B. breve had low adhesive ability
      regardless of carbon source. Despite differential binding ability, both HMO-grown
      strains significantly differentially affected the Caco-2 transcriptome compared
      to their glucose or lactose grown controls. HMO-grown B. breve and B. infantis
      both downregulated genes in Caco-2 cells associated with chemokine activity.
      CONCLUSION: The choice of carbon source affects the interaction of bifidobacteria
      with intestinal epithelial cells. HMO-grown bifidobacteria reduce markers of
      inflammation, compared to glucose or lactose-grown bifidobacteria. In the future,
      the design of preventative or therapeutic probiotic supplements may need to
      include appropriately chosen prebiotics.

PMID- 26303934
TI  - Absence of KMT2D/MLL2 mutations in abdominal paraganglioma.

PMID- 26303933
TI  - Transcranial magnetic stimulation for individual identification of the best
      electrode position for a motor imagery-based brain-computer interface.
AB  - BACKGROUND: For the translation of noninvasive motor imagery (MI)-based brain
      computer interfaces (BCIs) from the lab environment to end users at their homes,
      their handling must be improved. As a key component, the number of
      electroencephalogram (EEG)-recording electrodes has to be kept at a minimum.
      However, due to inter-individual anatomical and physiological variations,
      reducing the number of electrodes bares the risk of electrode misplacement, which
      will directly translate into a limited BCI performance of end users. The aim of
      the study is to evaluate the use of focal transcranial magnetic stimulation (TMS)
      as an easy tool to individually optimize electrode positioning for a MI-based
      BCI. For this, the area of MI-induced mu-rhythm modulation was compared with the
      motor hand representation area in respect to their localization and to the
      control performance of a MI-based BCI. METHODS: Focal TMS was applied to map the
      motor hand areas and a 48-channel high-resolution EEG was used to localize MI
      induced mu-rhythm modulations in 11 able-bodied, right-handed subjects (5 male,
      age: 23-31). The online BCI performances of the study participants were assessed
      with a single next-neighbor Laplace channel consecutively placed over the motor
      hand area and over the area of the strongest mu-modulation. RESULTS: For most
      subjects, a consistent deviation between the position of the mu-modulation center
      and the corresponding motor hand areas well above the localization error could be
      observed in mediolateral and to a lesser degree in anterior-posterior direction.
      On an individual level, the MI-induced mu-rhythm modulation was at average found
      1.6 cm (standard deviation (SD) = 1.30 cm) lateral and 0.31 cm anterior (SD =
      1.39 cm) to the motor hand area and enabled a significantly better online BCI
      performance than the motor hand areas. CONCLUSION: On an individual level a trend
      towards a consistent average spatial distance between motor hand area and mu
      rhythm modulation center was found indicating that TMS may be used as a simple
      tool for quick individual optimization of EEG-recording electrode positions of MI
      based BCIs. The study results indicate that motor hand areas of the primary motor
      cortex determined by TMS are not the main generators of the cortical mu-rhythm.

PMID- 26303935
TI  - Associations Between Maternal Infection During Pregnancy, Childhood Infections,
      and the Risk of Subsequent Psychotic Disorder--A Swedish Cohort Study of Nearly 2
      Million Individuals.
AB  - OBJECTIVE: Recent studies question whether the risk for psychotic disorder
      associated with prenatal exposure to infection are due to infections per se, or
      to shared susceptibility of both infections and psychiatric disorders. Moreover,
      the potential link between prenatal infection and serious infections during
      childhood, another alleged risk factor for psychotic disorder, remains unknown.
      The aim of this study was to investigate the role of maternal infections during
      pregnancy in context of parental psychiatric disorders and subsequent childhood
      infections. METHOD: All children born in Sweden 1978-1997 were linked to the
      National Patient Register. Hazard ratios of nonaffective psychosis were estimated
      in relation to maternal infection during pregnancy and odds ratios of childhood
      infection were calculated in relation to maternal infection during pregnancy.
      Relative excess risk due to interaction (RERI) estimated biological synergism
      between parental psychiatric disorder and maternal infection during pregnancy,
      and between maternal infection during pregnancy and childhood infection. RESULTS:
      Maternal infection during pregnancy was not statistically significantly
      associated with offspring psychosis (adjusted hazard ratio: 1.06, 95% CI 0.88
      1.27). However, maternal infection during pregnancy and maternal psychiatric
      disorders acted synergistically in offspring psychosis development (RERI 1.33,
      95% CI 0.27-2.38). Maternal infection during pregnancy increased the risk of
      offspring childhood infections (OR 1.50, 95% CI 1.45-1.54). These 2 factors also
      interacted in psychosis development (RERI 0.63, 95% CI 0.12-1.14). CONCLUSIONS:
      Among mothers with a history of psychiatric disease, infection during pregnancy
      increases the risk of psychosis in offspring. Maternal infections during
      pregnancy appear to contribute to the risk of childhood infections, which
      together render the child more vulnerable to psychosis development.

PMID- 26303937
TI  - Strategizing Safety: Theoretical Frameworks to Understand Women's Decision Making
      in the Face of Partner Violence and Social Inequities.
AB  - Women in physically and psychologically abusive relationships face numerous
      decisions related to their safety: decisions that historically have been viewed
      by researchers and human service practitioners as related to individual or
      interpersonal factors, such as how they feel about their partner, what they (or
      those they are close to) think is best for their children, or whether they have a
      safe place to go to. Social and structural factors, such as poverty, sexism, and
      barriers related to disability, are either left out or viewed at their individual
      level consequence, such as a woman's employment status. Using interview data and
      case studies from a larger study on housing instability, partner violence, and
      health, the authors apply ecological and macro-level theoretical models that go
      beyond the individual level to the stories of women who struggled with partner
      violence, arguing that it is critical to examine the large social and structural
      forces that impact women's lives if we are to understand the decisions women make
      when facing a violent partner.

PMID- 26303938
TI  - The Roles of Traditional Gender Myths and Beliefs About Beating on Self-Reported
      Partner Violence.
AB  - The aim of the current study was to investigate the roles of beliefs about
      beating, traditional gender myth endorsement, ambivalent sexism, and perceived
      partner violence in determining an individual's own reported violence toward his
      or her partner. The sample consisted of 205 (117 women; 88 men) Turkish and
      Turkish Cypriot undergraduate students, aged between 16 and 29 years.
      Participants completed measures of beliefs about beating, traditional gender myth
      endorsement, and ambivalent sexism and rated the extent to which they experienced
      abusive behaviors from their partner as well as the extent to which they were
      themselves abusive to their partners. Results showed that positive beliefs about
      beating, endorsing traditional gender myths, and experiencing partner abuse were
      all predictive of self-reported abuse to one's partner. Furthermore, the
      relationship between myth endorsement and self-abusive behavior was mediated by
      beliefs toward beating-only in men. Results are discussed in light of the
      traditional gender system evident in Turkish societal makeup.

PMID- 26303939
TI  - College Students' Reactions to Participating in Relational Trauma Research: A
      Mixed Methodological Study.
AB  - Using a mixed methodology, the present study compared men's and women's perceived
      benefits and emotional reactions with participating in research that inquired
      about child maltreatment and intimate partner violence (IPV) victimization and
      perpetration. Participants consisted of 703 college students (357 women, 346
      men), ages 18 to 25 who reported on their childhood maltreatment, adolescent and
      adult IPV victimization and perpetration, and their reactions (perceived benefits
      and emotional effects) to participating. Participants' reactions to participating
      were assessed using quantitative scales, as well as open-ended written responses
      that were content coded by researchers. Women reported more personal benefits
      from research, whereas men and women reported similar levels of emotional
      reactions to research participation. Furthermore, greater frequencies of child
      maltreatment and IPV victimization were related to higher levels of emotional
      reactions. Common self-identified reasons for emotional reactions (e.g., not
      liking to think about abuse in general, personal victimization experiences) and
      benefits (e.g., reflection and awareness about oneself, learning about IPV) were
      also presented and analyzed. These data underscore the importance of future
      research that examines the behavioral impact of research participation utilizing
      longitudinal and in-depth qualitative methodologies. Findings also highlight the
      potential psychoeducational value of research on understanding the reasons
      underlying participants' benefits and emotional effects.

PMID- 26303936
TI  - Effects of Fronto-Temporal Transcranial Direct Current Stimulation on Auditory
      Verbal Hallucinations and Resting-State Functional Connectivity of the Left
      Temporo-Parietal Junction in Patients With Schizophrenia.
AB  - Auditory verbal hallucinations (AVH) in patients with schizophrenia are
      associated with abnormal hyperactivity in the left temporo-parietal junction
      (TPJ) and abnormal connectivity between frontal and temporal areas. Recent
      findings suggest that fronto-temporal transcranial Direct Current stimulation
      (tDCS) with the cathode placed over the left TPJ and the anode over the left
      prefrontal cortex can alleviate treatment-resistant AVH in patients with
      schizophrenia. However, brain correlates of the AVH reduction are unclear. Here,
      we investigated the effect of tDCS on the resting-state functional connectivity
      (rs-FC) of the left TPJ. Twenty-three patients with schizophrenia and treatment
      resistant AVH were randomly allocated to receive 10 sessions of active (2 mA, 20
      min) or sham tDCS (2 sessions/d for 5 d). We compared the rs-FC of the left TPJ
      between patients before and after they received active or sham tDCS. Relative to
      sham tDCS, active tDCS significantly reduced AVH as well as the negative
      symptoms. Active tDCS also reduced rs-FC of the left TPJ with the left anterior
      insula and the right inferior frontal gyrus and increased rs-FC of the left TPJ
      with the left angular gyrus, the left dorsolateral prefrontal cortex and the
      precuneus. The reduction of AVH severity was correlated with the reduction of the
      rs-FC between the left TPJ and the left anterior insula. These findings suggest
      that the reduction of AVH induced by tDCS is associated with a modulation of the
      rs-FC within an AVH-related brain network, including brain areas involved in
      inner speech production and monitoring.

PMID- 26303940
TI  - Acquisition of the lac operon by Salmonella enterica.
AB  - BACKGROUND: Classical bacteriological characteristics of Salmonella enterica
      indicate that the members of this species are unable to utilize lactose as a
      carbon source. However, lactose-fermenting (Lac+) strains of several Salmonella
      serovars have been isolated from different foodborne outbreaks as well as
      different geographical regions worldwide. In the present study, we sequenced the
      genomes of 13 Lac + S. enterica isolates and characterized the lac region,
      comparing it to the lac region in other enteric bacterial species. RESULTS:
      Genetic analysis of the lac operons in the S. enterica genomes revealed that they
      all contain intact lacI, lacZ, and lacY genes. However, lacA was truncated in all
      of the S. enterica subsp. enterica isolates, encoding a 56 amino acid peptide
      rather than the full length 220 amino acid LacA protein. Molecular analyses of
      the 13 isolates revealed that the lac operon resided on a plasmid in some strains
      and in others was integrated into the bacterial chromosome. In most cases, an
      insertion sequence flanked at least one end of the operon. Interestingly, the S.
      enterica Montevideo and S. enterica Senftenberg isolates were found to harbor a
      plasmid with a high degree of sequence similarity to a plasmid from Klebsiella
      pneumoniae strain NK29 that also harbors the lac operon. In addition, two S.
      enterica Tennessee isolates carried two copies of the lac operon. Phylogenetic
      analysis based on lacIZY gene sequences determines distinct clusters, and reveals
      a greater correlation between lacIZY sequence and flanking organization than with
      either bacterial species or genomic location. CONCLUSIONS: Our results indicate
      that the lac region is highly mobile among Enterobacteriaceae and demonstrate
      that the Lac + S. enterica subsp. enterica serovars acquired the lac region
      through parallel events. The acquisition of the lac operon by several S. enterica
      serovars may be indicative of environmental adaptation by these bacteria.

PMID- 26303941
TI  - Celeribacter manganoxidans sp. nov., a manganese-oxidizing bacterium isolated
      from deep-sea sediment of a polymetallic nodule province.
AB  - A Gram-stain-negative, strictly aerobic, non-motile, rod-shaped, manganese
      oxidizing bacterial strain, designated DY2-5T, was isolated from surface sediment
      of Pacific Clarion-Clipperton Fracture Zone (CCFZ). Growth occurred at 0-37 
      degrees C (optimum 28  degrees C), pH 6.5-9.0 (optimum pH 7.0-7.5) and in the
      presence of 1-11% (w/v) NaCl (optimum 3-4%). Phylogenetic analysis based on 16S
      rRNA gene sequences revealed that the novel strain was most closely related to
      Celeribacter halophilus ZXM137T with 96.13% sequence similarity, and had 16S rRNA
      gene sequence similarities in the range 93.89-95.87% with other species of the
      genus Celeribacter. The dominant fatty acids were summed feature 8 (C18:1omega7c
      and/or C18:1omega6c) and C16:0. The polar lipids of strain DY2-5T comprised
      phosphatidylglycerol, phosphatidylcholine and two unknown aminolipids. The major
      respiratory quinone was ubiquinone-10 (Q-10). The DNA G+C content of strain DY2
      5T was 64.8 mol%. On the basis of the phenotypic, genotypic and physiological
      evidence, strain DY2-5T represents a novel species of the genus Celeribacter, for
      which the name Celeribacter manganoxidans sp. nov. is proposed. The type strain
      is DY2-5T ( = JCM 19384T = KCTC 32473T).

PMID- 26303942
TI  - Complicating the dominant morality discourse: mothers and fathers' constructions
      of substance use during pregnancy and early parenthood.
AB  - INTRODUCTION: Consumption of substances is a highly controversial behaviour, with
      those who do so commonly viewed as deviants, even criminals, or else as out of
      control addicts. In other work we showed that the use of substances by women who
      are pregnant or have recently become parents was mainly viewed by health and
      social care providers as morally wrong. Problematic substance use was framed
      through the narrow lens of gendered responsibilisation, resulting in women being
      seen primarily as foetal incubators and primary caregivers of infants. METHODS:
      In this follow-up paper we examine descriptive and qualitative data from a
      convenience sample of biological mothers and fathers (N = 34) recruited as part
      of a larger mixed methods study of the development and early implementation of an
      integrated primary maternity care program. We present a description of the
      participants' backgrounds, family circumstances, health status, and perception of
      drug-related stigma. This is succeeded by a thematic analysis of their personal
      views on substance use during both pregnancy and the transition to parenthood.
      RESULTS: Our results show that while many mothers and fathers hold abstinence as
      the ideal during pregnancy and early parenting, they simultaneously recognize the
      autonomy of women to judge substance use risk for themselves. Participants also
      call attention to social structural factors that increase/decrease harms
      associated with such substance use, and present an embodied knowledge of
      substance use based on their tacit knowledge of wellness and what causes harm.
      CONCLUSIONS: While these two main discourses brought forward by parents
      concerning the ideal of abstinence and the autonomy of women are not always
      reconcilable and are partially a reflection of the dissonance between dominant
      moral codes regarding motherhood and the lived experiences of people who use
      substances, service providers who are attuned to these competing discourses are
      likely to be more effective in their delivery of health and social services for
      vulnerable families. More holistic and nuanced perspectives of health, substance
      use, and parenting may generate ethical decision-making practice frameworks that
      guide providers in meeting and supporting the efforts of mothers and fathers to
      achieve well-being within their own definitions of problematic substance use.

PMID- 26303943
TI  - A machine-independent method to have active removal of 5,000 centistokes silicone
      oil using plastic infusion tube and 23-gauge microcannulas.
AB  - BACKGROUND: To describe one modified method of having machine-independent removal
      of 5,000 centistokes silicone oil through 23-gauge trocar-cannulas. METHODS:
      Consecutive patients with silicone oil tamponade for more than four months and
      with complete retinal reattachment were included. Two 23-gauge trocars were used
      to make sclerotomies while the microcannulas remained in situ for intravitreous
      infusion and silicone oil drainage. A short section of infusion tube was
      connected with a 10 ml syringe's needle adapter. The other side was attached to
      the conjunctiva surface and covered the cannula's cap inside to form a closed
      space for silicone oil drainage. The main outcomes were duration for complete
      removal of silicone oil and intra- and postoperative complications. RESULT: There
      were totally twenty cases (20 eyes) included. The mean time for draining out the
      silicone oil was 4.54 +/- 0.78 minutes. Intraoperatively, flute needle was
      introduced additionally in seven cases to achieve complete removal. No cases
      experienced postoperative visual acuity deterioration or refractory hypotony. No
      significant residual oil bubbles were observed. No retinal redetachment occurred
      throughout the follow-ups. CONCLUSION: The modified method of using an infusion
      tube and 23-gauge trocar-cannulas can achieve quick and complete removal of high
      viscosity silicone oil.

PMID- 26303944
TI  - IFDOTMETER: A New Software Application for Automated Immunofluorescence Analysis.
AB  - Most laboratories interested in autophagy use different imaging software for
      managing and analyzing heterogeneous parameters in immunofluorescence experiments
      (e.g., LC3-puncta quantification and determination of the number and size of
      lysosomes). One solution would be software that works on a user's laptop or
      workstation that can access all image settings and provide quick and easy-to-use
      analysis of data. Thus, we have designed and implemented an application called
      IFDOTMETER, which can run on all major operating systems because it has been
      programmed using JAVA (Sun Microsystems). Briefly, IFDOTMETER software has been
      created to quantify a variety of biological hallmarks, including mitochondrial
      morphology and nuclear condensation. The program interface is intuitive and user
      friendly, making it useful for users not familiar with computer handling. By
      setting previously defined parameters, the software can automatically analyze a
      large number of images without the supervision of the researcher. Once analysis
      is complete, the results are stored in a spreadsheet. Using software for high
      throughput cell image analysis offers researchers the possibility of performing
      comprehensive and precise analysis of a high number of images in an automated
      manner, making this routine task easier. 

PMID- 26303945
TI  - Mycobacterium massiliense Type II genotype leads to higher level of colony
      forming units and TNF-alpha secretion from human monocytes than Type I genotype.
AB  - Recently, we introduced a novel Mycobacterium massiliense Type II genotype from
      Korean patients, in which all isolates showed only a rough (R) colony morphotype.
      In this study, we sought to compare clinical factors and virulence potentials of
      two genotypes of M. massiliense, Type I and Type II. Patients infected with Type
      II tend to be younger at infection than those infected with Type I (56.7 vs 62.3,
      p = 0.051). Type II was more significantly related to R colony type than Type I
      (34.1% vs 94.1%, p < 0.001). The Type II strain showed significantly more colony
      forming units (CFUs) and higher levels of TNF-alpha secretion in infection of
      human monocytes than the Type I strain. The challenge of extracted
      glycopeptidolipid (GPL) into human monocytes indicated that the loss of GPL from
      the cell wall of the Type II genotype led to a higher level of TNF-alpha
      secretion in a toll-like receptor 2(TLR2)-dependent manner. Taken together, our
      data suggest that the M. massiliense Type II genotype shows higher virulence than
      Type I, which may be due to the induction of TNF-alpha via the loss of GPL from
      the Type II cell wall. 

PMID- 26303946
TI  - Insights into the segmental identity of post-oral commissures and pharyngeal
      nerves in Onychophora based on retrograde fills.
AB  - BACKGROUND: While the tripartite brain of arthropods is believed to have evolved
      by a fusion of initially separate ganglia, the evolutionary origin of the
      bipartite brain of onychophorans-one of the closest arthropod relatives-remains
      obscure. Clarifying the segmental identity of post-oral commissures and
      pharyngeal nerves might provide useful insights into the evolution of the
      onychophoran brain. We therefore performed retrograde fills of these commissures
      and nerves in the onychophoran Euperipatoides rowelli. RESULTS: Our fills of the
      anterior and posterior pharyngeal nerves revealed groups of somata that are
      mainly associated with the deutocerebrum. This resembles the innervation pattern
      of other feeding structures in Onychophora, including the jaws and several lip
      papillae surrounding the mouth. Our fills of post-oral commissures in E. rowelli
      revealed a graded arrangement of anteriorly shifted somata associated with post
      oral commissures #1 to #5. The number of deutocerebral somata associated with
      each commissure decreases posteriorly, i.e., commissure #1 shows the highest and
      commissure #5 the lowest numbers of associated somata, whereas none of the
      subsequent median commissures, beginning with commissure #6, shows somata located
      in the deutocerebrum. CONCLUSIONS: Based on the graded and shifted arrangement of
      somata associated with the anteriormost post-oral commissures, we suggest that
      the onychophoran brain, which is a bipartite syncerebrum, might have evolved by a
      successive anterior/anterodorsal migration of neurons towards the protocerebrum
      in the last onychophoran ancestor. This implies that the composite brain of
      onychophorans and the compound brain of arthropods might have independent
      evolutionary origins, as in contrast to arthropods the onychophoran syncerebrum
      is unlikely to have evolved by a fusion of initially separate ganglia.

PMID- 26303947
TI  - UTX inhibits EMT-induced breast CSC properties by epigenetic repression of EMT
      genes in cooperation with LSD1 and HDAC1.
AB  - The histone H3K27 demethylase, UTX, is a known component of the H3K4
      methyltransferase MLL complex, but its functional association with H3K4
      methylation in human cancers remains largely unknown. Here we demonstrate that
      UTX loss induces epithelial-mesenchymal transition (EMT)-mediated breast cancer
      stem cell (CSC) properties by increasing the expression of the SNAIL, ZEB1 and
      ZEB2 EMT transcription factors (EMT-TFs) and of the transcriptional repressor
      CDH1. UTX facilitates the epigenetic silencing of EMT-TFs by inducing competition
      between MLL4 and the H3K4 demethylase LSD1. EMT-TF promoters are occupied by c
      Myc and MLL4, and UTX recognizes these proteins, interrupting their
      transcriptional activation function. UTX decreases H3K4me2 and H3 acetylation at
      these promoters by forming a transcriptional repressive complex with LSD1, HDAC1
      and DNMT1. Taken together, our findings indicate that UTX is a prominent tumour
      suppressor that functions as a negative regulator of EMT-induced CSC-like
      properties by epigenetically repressing EMT-TFs. 

PMID- 26303950
TI  - Vibrational and coherence dynamics of molecules.
AB  - We analytically investigate the population and coherence dynamics and relaxations
      in the vibrational energy transport in molecules. The corresponding two time
      scales t1 and t2 are explored. Coherence-population entanglement is found to
      considerably promote the time scale t2 for dephasing and the amplitude of
      coherence. This is attributed to the suppression of the environment-induced drift
      force by coherence. Moreover the population imbalance (magnetization) is shown to
      be significantly amplified with the coherence-population entanglement. Contrary
      to the previous studies, we exactly elucidate a coherent process by showing t1 <
      t2. We predict the relaxation of vibrational and orientational dynamics of OH
      stretching modes in agreement with the recent experiments, when applied to the
      water molecules dissolved in D2O. Finally we explore the coherence effect on the
      heat current at the macroscopic level. 

PMID- 26303949
TI  - KDM6B Elicits Cell Apoptosis by Promoting Nuclear Translocation of FOXO1 in Non
      Small Cell Lung Cancer.
AB  - BACKGROUND/AIMS: Non-small cell lung carcinoma (NSCLC) is the most common type of
      lung cancer and the cause of most cancer-related deaths. The molecular mechanisms
      that are involved in NSCLC development are currently not well understood.
      Accumulating evidence shows that histone demethylases play important roles in the
      regulation of pathological developmental processes in many diseases, including
      various types of cancers. METHODS: Mitochondrial membrane potential assays,
      migration and invasion assays, caspase-3 and caspase-9 activity assays and
      western blot analysis were used in this research. RESULTS: We found that
      overexpression of KDM6B, a demethylase that acts on histone H3 at lysine 27
      (H3K27), inhibited cell growth by initiating mitochondria-dependent apoptosis and
      by attenuating the invasion-metastasis cascade in NSCLC cells. Moreover, our
      results showed that KDM6B directly interacted with FOXO1 and that overexpression
      of KDM6B promoted nuclear accumulation of FOXO1. The effects of KDM6B on cell
      apoptosis and metastasis were weakened by knockdown of FOXO1 expression. On the
      contrary, knocking down expression of KDM6B inhibited cell apoptosis and promoted
      cell growth by mitigating the nuclear translocation of FOXO1 in NSCLC cells.
      CONCLUSIONS: These findings suggest that KDM6B may act in a pro-apoptotic role in
      NSCLC by causing the nuclear translocation of FOXO1.

PMID- 26303948
TI  - MicroRNA-455 regulates brown adipogenesis via a novel HIF1an-AMPK-PGC1alpha
      signaling network.
AB  - Brown adipose tissue (BAT) dissipates chemical energy as heat and can counteract
      obesity. MicroRNAs are emerging as key regulators in development and disease.
      Combining microRNA and mRNA microarray profiling followed by bioinformatic
      analyses, we identified miR-455 as a new regulator of brown adipogenesis. miR-455
      exhibits a BAT-specific expression pattern and is induced by cold and the
      browning inducer BMP7. In vitro gain- and loss-of-function studies show that miR
      455 regulates brown adipocyte differentiation and thermogenesis. Adipose-specific
      miR-455 transgenic mice display marked browning of subcutaneous white fat upon
      cold exposure. miR-455 activates AMPKalpha1 by targeting HIF1an, and AMPK
      promotes the brown adipogenic program and mitochondrial biogenesis.
      Concomitantly, miR-455 also targets the adipogenic suppressors Runx1t1 and
      Necdin, initiating adipogenic differentiation. Taken together, the data reveal a
      novel microRNA-regulated signaling network that controls brown adipogenesis and
      may be a potential therapeutic target for human metabolic disorders. 

PMID- 26303951
TI  - Operative Time, Airway Management, Need for Blood Transfusions, and In-Hospital
      Stay for Bimaxillary, Intranasal, and Osseous Genioplasty Surgery: Current
      Clinical Practices.
AB  - PURPOSE: The purpose of this study was to assess operative time, perioperative
      airway management, early postoperative cardiopulmonary health, need for blood
      transfusion, and in-hospital stay associated with simultaneous bimaxillary,
      intranasal, and osseous genioplasty surgery. MATERIALS AND METHODS: The authors
      executed a retrospective cohort study derived from patients treated by 1 surgeon
      at a single institution from 2009 through 2014. The sample consisted of a
      consecutive series of patients with symptomatic chronic obstructed nasal
      breathing and a dentofacial deformity (DFD). All underwent at least a Le Fort I
      osteotomy, sagittal ramus osteotomies, septoplasty, inferior turbinate reduction,
      and osseous genioplasty. For each patient, the design of the osteotomies and the
      fixation techniques were consistent. The outcome variables included need for
      blood transfusion, operating time, success of nasotracheal intubation, time and
      place of extubation, early postoperative cardiopulmonary health, length of in
      hospital stay, and need for readmission after surgery. RESULTS: For the 166
      patients studied, the average age was 25 years (range, 13 to 65 yr; 87 female
      patients [52%]). The primary patterns of presenting DFD included long face (43 of
      166, 26%), maxillary deficiency (41 of 166, 25%), asymmetric mandibular excess
      (37 of 166, 22%), short face (28 of 166, 17%), and mandibular deficiency (15 of
      166, 9%). Forty-two patients (25%) were confirmed to have symptomatic obstructive
      sleep apnea. The open wound operating time averaged 2 hours 59 minutes (standard
      deviation, 32 minutes). Only 3 of the 166 patients (1.8%) received blood
      transfusions. All patients underwent successful nasotracheal intubation. Ninety
      six percent of patients were extubated in the operating room and the remaining 4%
      were extubated in the recovery room. No patients required reintubation or
      tracheostomy. One hundred thirty-seven patients (83%) were discharged after a 1-
      or 2-night in-hospital stay. Twenty-five (15%) required a 3-night stay and 4 (2%)
      required a 4-night hospital stay to achieve adequate oral intake. None of the
      patients required readmission. CONCLUSIONS: This study confirms efficient
      surgical and anesthesia care for patients undergoing simultaneous bimaxillary
      orthognathic, intranasal, and osseous genioplasty. Anticipating safe nasotracheal
      intubation with extubation soon after surgery and a limited need for blood
      transfusion has proved to be the norm. This study confirmed an average in
      hospital stay of 2 nights after complex orthognathic surgery without need for
      readmission.

PMID- 26303952
TI  - "I get hungry all the time": experiences of poverty and pregnancy in an urban
      healthcare setting in South Africa.
AB  - BACKGROUND: For pregnancy to result in a healthy mother and infant, women require
      adequate nutrition and to be able to access antenatal care, both of which require
      finances. While most women working in the formal sector in South Africa obtain
      some form of maternity leave, unemployed women receive no such support.
      Additional interventions in the form of expanded social assistance to vulnerable
      pregnant women are needed. To help inform such an approach, we undertook a series
      of qualitative interviews with low-income pregnant women in Johannesburg.
      METHODS: Qualitative, in-depth interviews were held with 22 pregnant women at a
      public sector antenatal clinic in Johannesburg in 2011 to gather data on their
      greatest needs and priorities during pregnancy, their access to financial
      resources to meet these needs, and the overall experience of poverty while
      pregnant. RESULTS: A total of 22 women were interviewed, 5 of whom were
      primagravid. One woman was in the first trimester of pregnancy, while nine were
      almost full-term. All but one of the pregnancies were unplanned. Most
      participants (15/22) were unemployed, two were employed and on paid maternity
      leave, and the remaining five doing casual, part-time work. In most cases,
      pregnancy reduced participants' earning potential and heightened reliance on
      their partners. Women not living with the father of their children generally
      received erratic financial support from them. The highest monthly expenses
      mentioned were food, accommodation and transport costs, and shortfalls in all
      three were reportedly common. Some participants described insufficient food in
      the household, and expressed concern about whether they were meeting the
      additional dietary requirements of pregnancy. Preparing for the arrival of a new
      baby was also a considerable source of anxiety, and was prioritized even above
      meeting women's own basic needs. CONCLUSIONS: Though pregnancy is a normal life
      occurrence, it has the potential to further marginalise women and children living
      in already vulnerable households. Extending the Child Support Grant to include
      the period of pregnancy would not only serve to acknowledge and address the
      particular challenges faced by poor women, but also go some way to securing the
      health of newborn children and future generations.

PMID- 26303953
TI  - Core pathways operating during methylotrophy of Bacillus methanolicus MGA3 and
      induction of a bacillithiol-dependent detoxification pathway upon formaldehyde
      stress.
AB  - Bacillus methanolicus MGA3 is a model facultative methylotroph of interest for
      fundamental research and biotechnological applications. Previous research
      uncovered a number of pathways potentially involved in one-carbon substrate
      utilization. Here, we applied dynamic (13) C labeling to elucidate which of these
      pathways operate during growth on methanol and to uncover potentially new ones.
      B. methanolicus MGA3 uses the assimilatory and dissimilatory ribulose
      monophosphate (RuMP) cycles for conversion of the central but toxic intermediate
      formaldehyde. Additionally, the operation of two cofactor-dependent formaldehyde
      oxidation pathways with distinct roles was revealed. One is dependent on tri- and
      tetraglutamylated tetrahydrofolate (THF) and is involved in formaldehyde
      oxidation during growth on methanol. A second pathway was discovered that is
      dependent on bacillithiol, a thiol cofactor present also in other Bacilli where
      it is known to function in redox-homeostasis. We show that bacillithiol-dependent
      formaldehyde oxidation is activated upon an upshift in formaldehyde induced by a
      substrate switch from mannitol to methanol. The genes and the corresponding
      enzymes involved in the biosynthesis of bacillithiol were identified by
      heterologous production of bacillithiol in Escherichia coli. The presented
      results indicate metabolic plasticity of the methylotroph allowing acclimation to
      fluctuating intracellular formaldehyde concentrations.

PMID- 26303954
TI  - Hemi-spatial neglect rehabilitation using non-invasive brain stimulation: or how
      to modulate the disconnection syndrome?
AB  - Hemi-spatial neglect syndrome is common and sometimes long-lasting. It is
      characterized by a deficit in the use and awareness of one side of space, most
      often consecutive to a right hemisphere injury, mainly in the parietal region.
      Acknowledging the different types and all clinical characteristics is essential
      for an appropriate evaluation and adapted rehabilitation care management,
      especially as it constitutes a predictive factor of a poor functional prognosis.
      Some new approaches have been developed in the last fifteen years in the field of
      hemi-spatial neglect rehabilitation, where non-invasive brain stimulation (TMS
      and tDCS) holds an important place. Today's approaches of unilateral spatial
      neglect modulation via non-invasive brain stimulation are essentially based on
      the concept of inter-hemispheric inhibition, suggesting an over-activation of the
      contralesional hemisphere due to a decrease of the inhibiting influences of the
      injured hemisphere. Several approaches may then be used: stimulation of the
      injured right hemisphere, inhibition of the hyperactive left hemisphere, or a
      combination of both. Results are promising, but the following complementary
      aspects must be refined before a more systematic application: optimal stimulation
      protocol, individual management according to the injured region, intensity,
      duration and frequency of care management, delay post-stroke before the beginning
      of treatment, combination of different approaches, as well as prognostic and
      efficacy criteria. An encouraging perspective for the future is the combination
      of several types of approaches, which would be largely facilitated by the
      improvement of fundamental knowledge on neglect mechanisms, which could in the
      future refine the choice for the most appropriate treatment(s) for a given
      patient. 

PMID- 26303955
TI  - Regenerative medicine. PBMCs stimulate chondrocyte migration and cartilage
      repair.

PMID- 26303956
TI  - Autoimmunity. Necrosis of IL-1beta-containing monocytes may drive NOMID.

PMID- 26303957
TI  - Adaptive sliding mode back-stepping pitch angle control of a variable
      displacement pump controlled pitch system for wind turbines.
AB  - A variable-displacement pump controlled pitch system is proposed to mitigate
      generator power and flap-wise load fluctuations for wind turbines. The pitch
      system mainly consists of a variable-displacement hydraulic pump, a fixed
      displacement hydraulic motor and a gear set. The hydraulic motor can be
      accurately regulated by controlling the pump displacement and fluid flows to
      change the pitch angle through the gear set. The detailed mathematical
      representation and dynamic characteristics of the proposed pitch system are
      thoroughly analyzed. An adaptive sliding mode pump displacement controller and a
      back-stepping stroke piston controller are designed for the proposed pitch system
      such that the resulting pitch angle tracks its desired value regardless of
      external disturbances and uncertainties. The effectiveness and control efficiency
      of the proposed pitch system and controllers have been verified by using
      realistic dataset of a 750 kW research wind turbine. 

PMID- 26303958
TI  - State estimation of stochastic non-linear hybrid dynamic system using an
      interacting multiple model algorithm.
AB  - In this work, state estimation schemes for non-linear hybrid dynamic systems
      subjected to stochastic state disturbances and random errors in measurements
      using interacting multiple-model (IMM) algorithms are formulated. In order to
      compute both discrete modes and continuous state estimates of a hybrid dynamic
      system either an IMM extended Kalman filter (IMM-EKF) or an IMM based derivative
      free Kalman filters is proposed in this study. The efficacy of the proposed IMM
      based state estimation schemes is demonstrated by conducting Monte-Carlo
      simulation studies on the two-tank hybrid system and switched non-isothermal
      continuous stirred tank reactor system. Extensive simulation studies reveal that
      the proposed IMM based state estimation schemes are able to generate fairly
      accurate continuous state estimates and discrete modes. In the presence and
      absence of sensor bias, the simulation studies reveal that the proposed IMM
      unscented Kalman filter (IMM-UKF) based simultaneous state and parameter
      estimation scheme outperforms multiple-model UKF (MM-UKF) based simultaneous
      state and parameter estimation scheme. 

PMID- 26303959
TI  - Characterization of Cu/Zn-SOD enzyme activities and gene expression in soybean
      under low nitrogen stress.
AB  - BACKGROUND: Superoxide dismutase (SOD) plays an important role in antioxidant
      defense in nearly all cells, and is speculated to be closely related to plant
      resistance to biotic and abiotic stresses, such as drought, salt, heavy metal and
      pathogen attack. However, little is known about the effects of SOD activity and
      its isoenzymes on low nitrogen stress tolerance and its effects on adaptability
      of plants to nitrogen limitation. RESULTS: Ten SOD isoenzymes were identified in
      soybean root, stem, leaf and mature seed, and were classified into three families
      (alpha.1, beta.1-4 and gamma.1-5). SOD activity was significantly elevated in
      soybean leaf and root. Conversely, under low-nitrogen conditions, only beta.2
      isoenzyme activity, belonging to the Cu/Zn-SOD family, was induced obviously in
      the root of soybean cultivar cv. WS01-15. Moreover, the expression of three Cu/Zn
      SOD genes was analyzed under low nitrogen stress. GmCZ-SOD1 gene was induced
      significantly in soybean root under low nitrogen stress. Interestingly,
      evolutionary analysis showed that this gene underwent a strong artificial
      selection during soybean domestication, suggesting that the Cu/Zn-SOD gene plays
      an essential role in the adaptive evolution of soybean nitrogen limitation
      resistance. CONCLUSION: GmCZ-SOD is important for adaptability of soybean to
      nitrogen limitation and these results provide useful information to unravel its
      biological role in low nitrogen resistance in plants. (c) 2015 Society of
      Chemical Industry.

PMID- 26303960
TI  - Depression and anxiety during the perinatal period.
AB  - BACKGROUND: Mood and anxiety and related disorders (AD) account for a significant
      proportion of mental health conditions, with close to 30 % of the population
      (28.8 %) suffering from an AD at some time in their life, and over fifteen
      percent (16.2 %) suffering from a mood disorder. The existing empirical
      literature leaves a number of important gaps with respect to our understanding of
      mood, anxiety and stress related difficulties among pregnant and postpartum
      women. The objective of this research is to address these. METHODS: Participants
      were 660 English-speaking pregnant women. Participants for the portion of the
      research estimating the prevalence/incidence of perinatal mood disorders and AD
      (N = 347) were recruited proportionally from a geographically defined area. All
      participants were recruited via prenatal clinic visits at hospitals, physician
      offices and midwifery clinics, and via community outreach at events and through
      word of mouth. Recruitment took place between November 9, 2007 and November 12,
      2010. Participants were administered questionnaires prenatally at two time points
      (approximately 24 and 33 weeks gestation) and again at 4-6 weeks' postpartum and
      6-months postpartum. Prevalence/incidence study participants who screened above
      cut-off on one or more of the 4-6 week mood and anxiety questionnaires were also
      administered a diagnostic interview for mood disorders and AD at approximately 8
      12 weeks postpartum. DISCUSSION: This research addresses a number of gaps in our
      understanding of mood, anxiety and stress among pregnant and postpartum women.
      Specifically, gaps in our knowledge regarding the prevalence and incidence of (a)
      AD and mood disorders, and (b) anxiety and stress among women experiencing a
      medically high-risk pregnancy, interest in stress management training in
      pregnancy, mental health treatment barriers and access and screening for anxiety
      among pregnant and postpartum women are addressed. The findings from this series
      of studies have the potential to improve screening, assessment and treatment of
      mood and anxiety problems suffered by pregnant and postpartum women.

PMID- 26303961
TI  - A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen.
AB  - The identification of human broadly neutralizing antibodies (bnAbs) targeting the
      hemagglutinin (HA) stem revitalized hopes of developing a universal influenza
      vaccine. Using a rational design and library approach, we engineered stable HA
      stem antigens ("mini-HAs") based on an H1 subtype sequence. Our most advanced
      candidate exhibits structural and bnAb binding properties comparable to those of
      full-length HA, completely protects mice in lethal heterologous and
      heterosubtypic challenge models, and reduces fever after sublethal challenge in
      cynomolgus monkeys. Antibodies elicited by this mini-HA in mice and nonhuman
      primates bound a wide range of HAs, competed with human bnAbs for HA stem
      binding, neutralized H5N1 viruses, and mediated antibody-dependent effector
      activity. These results represent a proof of concept for the design of HA stem
      mimics that elicit bnAbs against influenza A group 1 viruses. 

PMID- 26303963
TI  - Carcass traits and meat fatty acid composition of Barbarine lambs reared on
      rangelands or indoors on hay and concentrate.
AB  - The objective of this study was to compare carcass and meat quality between
      Barbarine lambs raised on rangelands and those reared indoors. A total of 24
      weaned male lambs (23.2 kg) were allotted into two groups. The first group (GS)
      grazed pasture dominated by natural shrubs and was supplemented with 100 g of
      concentrate. The second group (HS) received oat hay and 200 to 300 g supplement
      of the same concentrate in order to obtain the same average daily gain (ADG) as
      the GS group. Six lambs from each group were slaughtered. Lambs to be slaughtered
      were randomly identified at the beginning of the trial. Carcass traits (offals
      percentage, dressing percentage, cuts yield, tissue composition, fatness and
      conformation) were determined; pH and meat and fat color were measured. Samples
      from longissimus lumborum were collected to analyze fatty acid composition. The
      GS group was characterized by a higher offals percentage, associated with higher
      lungs, heart, liver and kidney percentage. Carcass dressing percentage defined as
      the rate between hot carcass weight and empty BW was lower by 3.4% in the GS
      group. No differences were observed for carcass meat yield and carcass and leg
      compactness. Shoulder bone percentage of the GS group was higher, without
      differences in fat and lean percentages. Fat thickness, kidney and tail fats were
      lower in the GS lambs. However, intramuscular fat content was not affected.
      Percentages of saturated fatty acids and polyunsaturated fatty acids (PUFA) were
      not modified, whereas levels of n-3 and long n-3PUFA (EPA, DPA and DHA) as well
      as Delta5 desaturase plus Delta6 desaturase index were higher for the GS group.
      Thrombogenic and atherogenic indexes were not altered. No significant effects
      were observed for meat pH, meat and fat color. Despite having the same ADG, lambs
      from the GS group were less fatty, and their meat was richer in beneficial fatty
      acids. 

PMID- 26303964
TI  - Vemurafenib-associated Dupuytren- and Ledderhose palmoplantar fibromatosis in
      metastatic melanoma patients.
AB  - BACKGROUND: The BRAF-inhibitor vemurafenib, used in patients with metastatic
      melanoma, induces multiple cutaneous side-effects. OBJECTIVE: The aim of this
      work was to evaluate the development of palmoplantar fibromatosis in a population
      of patients treated with the BRAF inhibitor vemurafenib. METHODS: Between April
      2011 and February 2013, we initiated a treatment with vemurafenib in 53 patients
      with an unresectable stage IIIC or stage IV melanoma. The patients were followed
      up on a regular base to monitor possible side-effects. RESULTS: A plantar or
      palmar fibromatosis was observed in five of 53 patients treated with vemurafenib.
      In four of these patients other risk factors for the development of palmoplantar
      fibromatosis were absent. CONCLUSION: The BRAF-inhibitor vemurafenib might induce
      palmoplantar fibromatosis.

PMID- 26303965
TI  - Behavioural innovation and cultural transmission of communication signal in black
      howler monkeys.
AB  - Social traditions based on communication signals are widespread in birds,
      cetaceans and humans, but surprisingly rare in nonhuman primates known for having
      genetically-determined vocal repertoires. This study presents the first
      description of a singular case of behaviour associated with calling (placing a
      hand in front of the mouth while vocalizing: HFM) in black howler monkeys. We
      showed, first, that HFM was found only in a subset of the groups observed, at the
      same geographical location, and was age- and sex-specific. There was an audience
      effect on HFM, with highest rates when a neighbouring group was visible. HFM was
      non-randomly combined with audio-visual signals and always performed while
      roaring. High HFM rates triggered more vocal responses from group members and
      male neighbours, and HFM signalers temporally synchronized their behaviour in a
      predictable way. Finally, the positioning of the hand systematically modified the
      call's auditory structure. Altogether these results support the idea that HFM is
      an innovated, culturally transmitted communication signal that may play a role in
      inter-group competition and intra-group cohesion. This study opens new lines of
      research about how nonhuman primates developed strategies to overcome their
      constraints in acoustic plasticity very early in the primate lineage. 

PMID- 26303966
TI  - Smoking cessation outcomes of referral to a specialist hospital outpatient
      clinic.
AB  - BACKGROUND AND OBJECTIVES: Hospital visits are an opportunity to engage smokers
      in tobacco treatment. However, little is known about engagement in follow-up
      referrals. The purpose of this study is to report the rates of program engagement
      and smoking cessation outcomes of patients referred to a specialist outpatient
      tobacco treatment program after a hospital visit or other referral. METHODS: A
      retrospective chart review was used to examine the outcomes of 486 participants
      referred to a hospital-based smoking cessation clinic provided by tobacco
      treatment specialists. Referral sources, demographics and smoking, medical,
      psychiatric, and substance use history were obtained. The main outcomes of
      interest were engagement in the program and 7-day point-prevalence of smoking
      abstinence. RESULTS: Sixty-eight percent of participants who were referred to the
      program were considered "engaged," of which 70% were from hospitals, 4% from
      community programs, 11% were from general practitioners, and 16% were self
      referrals. Thirty-percent (98/331) of engagers were abstinent by time of chart
      review (30% from the hospital, 8% from community programs, 19% from general
      practitioners, and 39% of self-referrals). Having quit for 1 month or longer at
      the past quit attempt, greater confidence in quitting smoking, lower expired
      carbon monoxide levels at baseline, and greater duration in the program were
      significant predictors of successful smoking cessation. DISCUSSION AND
      CONCLUSION: Providing tobacco treatment follow-up and referral for smokers after
      a hospital visit is important to enhance smoking cessation efforts. SCIENTIFIC
      SIGNIFICANCE: Referral to evidence-based tobacco treatment after hospital visits
      is effective. Models of tobacco treatment based on sources of referral should
      further be explored.

PMID- 26303962
TI  - The use of angiogenic biomarkers in maternal  blood to identify which SGA fetuses
      will require a  preterm delivery and mothers who will develop  pre-eclampsia.
AB  - OBJECTIVE: To determine (1) whether maternal plasma concentrations of angiogenic
      and anti-angiogenic factors can predict which mothers diagnosed with "suspected
      small for gestational age fetuses (sSGA)" will develop pre-eclampsia (PE) or
      require an indicated early preterm delivery (<= 34 weeks of gestation); and (2)
      whether risk assessment performance is improved using these proteins in addition
      to clinical factors and Doppler parameters. METHODS: This prospective cohort
      study included women with singleton pregnancies diagnosed with sSGA (estimated
      fetal weight <10th percentile) between 24 and 34 weeks of gestation (n = 314).
      Plasma concentrations of soluble vascular endothelial growth factor receptor-1
      (sVEGFR-1), soluble endoglin (sEng) and placental growth factor (PlGF) were
      determined in maternal blood obtained at the time of diagnosis. Doppler
      velocimetry of the umbilical (Umb) and uterine (UT) arteries was performed. The
      outcomes were (1) subsequent development of PE; and (2) indicated preterm
      delivery at <= 34 weeks of gestation (excluding deliveries as a result of
      spontaneous preterm labor, preterm pre-labor rupture of membranes or
      chorioamnionitis). RESULTS: (1) The prevalence of PE and indicated preterm
      delivery was 9.2% (n = 29/314) and 7.3% (n = 23/314), respectively; (2) the area
      under the receiver operating characteristic curve (AUC) for the identification of
      patients who developed PE and/or required indicated preterm delivery was greater
      than 80% for the UT artery pulsatility index (PI) z-score and each biochemical
      marker (including their ratios) except sVEGFR-1 MoM; (3) using cutoffs at a false
      positive rate of 15%, women with abnormal plasma concentrations of
      angiogenic/anti-angiogenic factors were 7-13 times more likely to develop PE, and
      12-22 times more likely to require preterm delivery than those with normal plasma
      MoM concentrations of these factors; (4) sEng, PlGF, PIGF/sEng and PIGF/sVEGFR-1
      ratios MoM, each contributed significant information about the risk of PE beyond
      that provided by clinical factors and/or Doppler parameters: women who had low
      MoM values for these biomarkers were at 5-9 times greater risk of developing PE
      than women who had normal values, adjusting for clinical factors and Doppler
      parameters (adjusted odds ratio for PlGF: 9.1, PlGF/sEng: 5.6); (5) the
      concentrations of sVEGFR-1 and PlGF/sVEGFR-1 ratio MoM, each contributed
      significant information about the risk of indicated preterm delivery beyond that
      provided by clinical factors and/or Doppler parameters: women who had abnormal
      values were at 8-9 times greater risk for indicated preterm delivery, adjusting
      for clinical factors and Doppler parameters; and (6) for a two-stage risk
      assessment (Umb artery Doppler followed by Ut artery Doppler plus biochemical
      markers), among women who had normal Umb artery Doppler velocimetry (n = 279), 21
      (7.5%) developed PE and 11 (52%) of these women were identified by an abnormal UT
      artery Doppler mean PI z-score (>2SD): a combination of PlGF/sEng ratio MoM
      concentration and abnormal UT artery Doppler velocimetry increased the
      sensitivity of abnormal UT artery Doppler velocimetry to 76% (16/21) at a fixed
      false-positive rate of 10% (p = 0.06). CONCLUSION: Angiogenic and anti-angiogenic
      factors measured in maternal blood between 24 and 34 weeks of gestation can
      identify the majority of mothers diagnosed with "suspected SGA" who subsequently
      developed PE or those who later required preterm delivery <= 34 weeks of
      gestation. Moreover, incorporation of these biochemical markers significantly
      improves risk assessment performance for these outcomes beyond that of clinical
      factors and uterine and umbilical artery Doppler velocimetry.

PMID- 26303968
TI  - Three-dimensional in vitro measurements of tooth wear using fluoridated
      dentifrices.
AB  - BACKGROUND: The aim of this study was to compare differences in wear of human
      enamel and dentine in vitro using a 3D measurement method comparing silica versus
      non-silica containing fluoridated dentifrices (Colgate Total(TM) [CT] or Fluor
      Protector Gel(TM) [FPG]). METHODS: Mounted native enamel (n = 36) and polished
      dentine (n = 36) samples were subjected to 10 wear cycles. Each cycle consisted
      of: (1) 1 hour remineralization in artificial saliva (AS); (2) 10 minute erosion
      (0.3% citric acid; pH = 2.8); (3) 2 minute toothbrush abrasion in AS (G1,
      control) or a slurry of 3:1 by weight of AS:dentifrice (G2 = CT; G3 = FPG) under
      a load of 2 N. Each group contained 12 enamel and 12 dentine samples. Paired pre-
      and post-wear scans made with a contacting scanner were digitally superimposed
      using ball bearings as datum. RESULTS: Mean and (SD) enamel wear was G1 = 21.9
      MUm (6.4); G2 = 15.2 MUm (2.8); G3 = 16.9 MUm (3.2). Enamel wear was not
      different between dentifrices (p = 0.99). Both dentifrices resulted in less
      enamel wear compared to the control (p < 0.05). Dentine wear was G1 = 41.3 MUm
      (8.1); G2 = 29.1 MUm (4.4); G3 = 22.1 MUm (3.5). Differences in measurements were
      observed between dentifrices and control (p < 0.05) and between dentifrices (p =
      0.014) with FPG showing less dentine wear than CT. CONCLUSIONS: FPG offered
      protection against erosive/abrasive tooth wear in dentine compared to CT. FPG did
      not offer such protective effect on enamel wear.

PMID- 26303967
TI  - The effectiveness of passive physical modalities for the management of soft
      tissue injuries and neuropathies of the wrist and hand: a systematic review by
      the Ontario Protocol for Traffic Injury Management (OPTIMa) collaboration.
AB  - OBJECTIVE: The purpose of this systematic review was to determine the
      effectiveness of passive physical modalities compared to other interventions,
      placebo/sham interventions, or no intervention in improving self-rated recovery,
      functional recovery, clinical outcomes and/or administrative outcomes (eg, time
      of disability benefits) in adults and/or children with soft tissue injuries and
      neuropathies of the wrist and hand. METHODS: We systematically searched MEDLINE,
      EMBASE, PsycINFO, and the Cochrane Central Register of Controlled Trials,
      accessed through Ovid Technologies, Inc, and CINAHL Plus with Full Text, accessed
      through EBSCO host, from 1990 to 2015. Our search strategies combined controlled
      vocabulary relevant to each database (eg, MeSH for MEDLINE) and text words
      relevant to our research question and the inclusion criteria. Randomized
      controlled trials, cohort studies, and case-control studies were eligible. Random
      pairs of independent reviewers screened studies for relevance and critically
      appraised relevant studies using the Scottish Intercollegiate Guidelines Network
      criteria. Studies with low risk of bias were synthesized following best evidence
      synthesis principles. RESULTS: We screened 6618 articles and critically appraised
      11 studies. Of those, 7 had low risk of bias: 5 addressed carpal tunnel syndrome
      (CTS) and 2 addressed de Quervain disease. We found evidence that various types
      of night splints lead to similar outcomes for the management of CTS. The evidence
      suggests that a night wrist splint is less effective than surgery in the short
      term but not in the long term. Furthermore, a night wrist splint and needle
      electroacupuncture lead to similar outcomes immediately postintervention.
      Finally, low-level laser therapy and placebo low-level laser therapy lead to
      similar outcomes. The evidence suggests that kinesio tape or a thumb spica cast
      offers short-term benefit for the management of de Quervain disease. Our search
      did not identify any low risk of bias studies examining the effectiveness of
      passive physical modalities for the management of other soft tissue injuries or
      neuropathies of the wrist and hand. CONCLUSIONS: Different night orthoses
      provided similar outcomes for CTS. Night orthoses offer similar outcomes to
      electroacupuncture but are less effective than surgery in the short term. This
      review suggests that kinesio tape or a thumb spica cast may offer short-term
      benefit for the management of de Quervain disease.

PMID- 26303969
TI  - N-acetyl cysteine inhibits H2O2-mediated reduction in the mineralization of MC3T3
      E1 cells by down-regulating Nrf2/HO-1 pathway.
AB  - There are controversial findings regarding the roles of nuclear factor (erythroid
      derived 2)-like 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway on bone metabolism under
      oxidative stress. We investigated how Nrf2/HO-1 pathway affects osteoblast
      differentiation of MC3T3-E1 cells in response to hydrogen peroxide (H2O2), N
      acetyl cysteine (NAC), or both. Exposing the cells to H2O2 decreased the alkaline
      phosphatase activity, calcium accumulation, and expression of osteoblast markers,
      such as osteocalcin and runt-related transcription factor-2. In contrast, H2O2
      treatment increased the expression of Nrf2 and HO-1 in the cells. Treatment with
      hemin, a chemical HO-1 inducer, mimicked the inhibitory effect of H2O2 on
      osteoblast differentiation by increasing the HO-1 expression and decreasing the
      osteogenic marker genes. Pretreatment with NAC restored all changes induced by
      H2O2 to near normal levels in the cells. Collectively, our findings suggest that
      H2O2-mediated activation of Nrf2/HO-1 pathway negatively regulates the osteoblast
      differentiation, which is inhibited by NAC.

PMID- 26303970
TI  - Epigenetic silencing of olfactomedin-4 enhances gastric cancer cell invasion via
      activation of focal adhesion kinase signaling.
AB  - Downregulation of olfactomedin-4 (OLFM4) is associated with tumor progression,
      lymph node invasion and metastases. However, whether or not downregulation of
      OLFM4 is associated with epigenetic silencing remains unknown. In this study, we
      investigate the role of OLFM4 in gastric cancer cell invasion. We confirm the
      previous result that OLFM4 expression is increased in gastric cancer tissues and
      decreases with an increasing number of metastatic lymph nodes, which are
      associated with OLFM4 promoter hypermethylation. Overexpression of OLFM4 in
      gastric cancer cells had an inhibitory effect on cell invasion. Furthermore, we
      found that focal adhesion kinase (FAK) was negatively correlated with OLFM4 in
      regards to lymph node metastasis in gastric cancer tissues. Also, inhibition of
      FAK induced by OLFM4 knockdown resulted in a decrease in cell invasion. Thus, our
      study demonstrates that epigenetic silencing of OLFM4 enhances gastric cancer
      cell invasion via activation of FAK signaling.

PMID- 26303971
TI  - A systematic mRNA control mechanism for germline stem cell homeostasis and cell
      fate specification.
AB  - Germline stem cells (GSCs) are the best understood adult stem cell types in the
      nematode Caenorhabditis elegans, and have provided an important model system for
      studying stem cells and their cell fate in vivo, in mammals. In this review, we
      propose a mechanism that controls GSCs and their cell fate through selective
      activation, repression and mobilization of the specific mRNAs. This mechanism is
      acutely controlled by known signal transduction pathways (e.g., Notch signaling
      and Ras-ERK MAPK signaling pathways) and P granule (analogous to mammalian germ
      granule)-associated mRNA regulators (FBF-1, FBF-2, GLD-1, GLD-2, GLD-3, RNP-8 and
      IFE-1). Importantly, all regulators are highly conserved in many multi-cellular
      animals. Therefore, GSCs from a simple animal may provide broad insight into
      vertebrate stem cells (e.g., hematopoietic stem cells) and their cell fate
      specification. [BMB Reports 2016; 49(2): 93-98]. 

PMID- 26303972
TI  - Amino-terminal arginylation as a degradation signal for selective autophagy.
AB  - The ubiquitin-proteasome system and the autophagy lysosome system are the two
      major protein degradation machineries in eukaryotic cells. These two systems
      coordinate the removal of unwanted intracellular materials, but the mechanism by
      which they achieve this synchronization is largely unknown. The ubiquitination of
      substrates serves as a universal degradation signal for both systems. Our study
      revealed that the amino-terminal Arg, a canonical N-degron in the ubiquitin
      proteasome system, also acts as a degradation signal in autophagy. We showed that
      many ER residents, such as BiP, contain evolutionally conserved arginylation
      permissive pro-N-degrons, and that certain inducers like dsDNA or proteasome
      inhibitors cause their translocation into the cytoplasm where they bind misfolded
      proteins and undergo amino-terminal arginylation by arginyl transferase 1 (ATE1).
      The amino-terminal Arg of BiP binds p62, which triggers p62 oligomerization and
      enhances p62-LC3 interaction, thereby stimulating autophagic delivery and
      degradation of misfolded proteins, promoting cell survival. This study reveals a
      novel ubiquitin-independent mechanism for the selective autophagy pathway, and
      provides an insight into how these two major protein degradation pathways
      communicate in cells to dispose the unwanted proteins.

PMID- 26303974
TI  - A Predictive Score for Bronchopleural Fistula Established Using the French
      Database Epithor.
AB  - BACKGROUND: Bronchopleural fistula (BPF) remains a rare but fatal complication of
      thoracic surgery. The aim of this study was to develop and validate a predictive
      model of BPF after pulmonary resection and to identify patients at high risk for
      BPF. METHODS: From January 2005 to December 2012, 34,000 patients underwent major
      pulmonary resection (lobectomy, bilobectomy, or pneumonectomy) and were entered
      into the French National database Epithor. The primary outcome was the occurrence
      of postoperative BPF at 30 days. The logistic regression model was built using a
      backward stepwise variable selection. RESULTS: Bronchopleural fistula occurred in
      318 patients (0.94%); its prevalence was 0.5% for lobectomy (n = 139), 2.2% for
      bilobectomy (n = 39), and 3% for pneumonectomy (n = 140). The mortality rate was
      25.9% for lobectomy (n = 36), 16.7% for bilobectomy (n = 6), and 20% for
      pneumonectomy (n = 28). In the final model, nine variables were selected: sex,
      body mass index, dyspnea score, number of comorbidities per patient, bilobectomy,
      pneumonectomy, emergency surgery, sleeve resection, and the side of the
      resection. In the development data set, the C-index was 0.8 (95% confidence
      interval: 0.78 to 0.82). This model was well calibrated because the Hosmer
      Lemeshow test was not significant (chi(2) = 10.5, p = 0.23). We then calculated
      the logistic regression coefficient to build the predictive score for BPF.
      CONCLUSIONS: This strong model could be easily used by surgeons to identify
      patient at high risk for BPF. This score needs to be confirmed prospectively in
      an independent cohort.

PMID- 26303975
TI  - Early Detection of Foot-And-Mouth Disease Virus from Infected Cattle Using A Dry
      Filter Air Sampling System.
AB  - Foot-and-mouth disease (FMD) is a highly contagious livestock disease of high
      economic impact. Early detection of FMD virus (FMDV) is fundamental for rapid
      outbreak control. Air sampling collection has been demonstrated as a useful
      technique for detection of FMDV RNA in infected animals, related to the
      aerogenous nature of the virus. In the current study, air from rooms housing
      individual (n = 17) or two groups (n = 4) of cattle experimentally infected with
      FDMV A24 Cruzeiro of different virulence levels was sampled to assess the
      feasibility of applying air sampling as a non-invasive, screening tool to
      identify sources of FMDV infection. Detection of FMDV RNA in air was compared
      with first detection of clinical signs and FMDV RNA levels in serum and oral
      fluid. FMDV RNA was detected in room air samples 1-3 days prior (seven animals)
      or on the same day (four animals) as the appearance of clinical signs in 11 of 12
      individually housed cattle. Only in one case clinical signs preceded detection in
      air samples by one day. Overall, viral RNA in oral fluid or serum preceded
      detection in air samples by 1-2 days. Six individually housed animals inoculated
      with attenuated strains did not show clinical signs, but virus was detected in
      air in one of these cases 3 days prior to first detection in oral fluid. In
      groups of four cattle housed together, air detection always preceded appearance
      of clinical signs by 1-2 days and coincided more often with viral shedding in
      oral fluid than virus in blood. These data confirm that air sampling is an
      effective non-invasive screening method for detecting FMDV infection in confined
      to enclosed spaces (e.g. auction barns, milking parlours). This technology could
      be a useful tool as part of a surveillance strategy during FMD prevention,
      control or eradication efforts.

PMID- 26303973
TI  - Transcriptional regulatory network during development in the olfactory
      epithelium.
AB  - Regeneration, a process of reconstitution of the entire tissue, occurs throughout
      life in the olfactory epithelium (OE). Regeneration of OE consists of several
      stages: proliferation of progenitors, cell fate determination between neuronal
      and non-neuronal lineages, their differentiation and maturation. How the
      differentiated cell types that comprise the OE are regenerated, is one of the
      central questions in olfactory developmental neurobiology. The past decade has
      witnessed considerable progress regarding the regulation of transcription factors
      (TFs) involved in the remarkable regenerative potential of OE. Here, we review
      current state of knowledge of the transcriptional regulatory networks that are
      powerful modulators of the acquisition and maintenance of developmental stages
      during regeneration in the OE. Advance in our understanding of regeneration will
      not only shed light on the basic principles of adult plasticity of cell identity,
      but may also lead to new approaches for using stem cells and reprogramming after
      injury or degenerative neurological diseases.

PMID- 26303976
TI  - Peers as Facilitators of Medication Adherence Interventions: A Review.
AB  - BACKGROUND: Difficulty taking essential medications as prescribed is a prevalent
      problem among people living with chronic diseases. Numerous interventions to
      enhance medication adherence have been developed; the majority facilitated by
      health care professionals. OBJECTIVE: This review examined medication adherence
      interventions delivered by peers (ie, lay individuals living with the same
      chronic disease) and reports what is known about the impact of peer-facilitated
      interventions. DATA SOURCES: PubMed, CINAHL, Google Scholar, Google, and
      PsychInfo, and ancestry searches. STUDY SELECTION: Solely peers delivered the
      intervention and follow-up occurred for at least 24 weeks postintervention.
      Electronic databases were searched from their start date to December 31, 2014.
      RESULTS: Eleven studies were located that reported 10 different interventions
      focused on 6 chronic disease conditions. Most interventions were delivered in
      clinical settings and grounded in a theoretical framework. Formats were evenly
      split between individual and group level, with one intervention using both.
      Length of training for the interventionists and the number of intervention
      sessions that subjects received varied across studies. LIMITATIONS: Self-report
      was frequently used as a measure of adherence. Biomarkers were sometimes used to
      assess medication adherence; however, lifestyle modification may have also
      affected biomarker levels. CONCLUSIONS: Overall, the interventions had positive
      effects and attrition was quite low. Peer-facilitated interventions appear to
      enhance medication adherence as well as other healthful behaviors, such as
      exercise.

PMID- 26303977
TI  - Time Savings with Once-Monthly C.E.R.A.:  A Time and Motion Study Conducted in 
      13 Haemodialysis Centres in Italy.
AB  - BACKGROUND: We sought to document the time required by health care professionals
      to administer erythropoiesis-stimulating agents (ESAs) and continuous
      erythropoiesis receptor activator (C.E.R.A.) in the management of renal anaemia.
      METHODS: A Time and Motion study was conducted in 13 centres in Italy. The time
      spent on preparation, distribution, and injection for both ESA and C.E.R.A.
      groups was measured. A multilevel model was run to account for the centre
      clustering effect. RESULTS: The average number of ESA injections/patient/year was
      89. The average uptake of C.E.R.A. was 26%. The average time per session was 1.54
      min for ESA (95% CI 1.21-1.86) vs. 1.64 min for C.E.R.A. (95% CI 1.31-1.97).
      Estimated time/patient/year was 137 min for ESA and 20 min for C.E.R.A. Assuming
      a 100% uptake of C.E.R.A., annual time savings/centre would be 84% (194 h).
      CONCLUSIONS: Substantial annual time savings on frequent anaemia management
      related tasks were found when a switchover was made from ESAs to C.E.R.A.

PMID- 26303978
TI  - Epigenetic variation in the serotonin transporter gene predicts resting state
      functional connectivity strength within the salience-network.
AB  - Genetic variation in the serotonin transporter gene (SLC6A4) has been associated
      with psychopathology and aberrant brain functioning in a plethora of clinical and
      imaging studies. In contrast, the neurobiological correlates of epigenetic
      signatures in SLC6A4, such as DNA methylation profiles, have only recently been
      explored in human brain imaging research. The present study is the first to apply
      a resting state functional magnetic resonance imaging approach to identify
      changes in brain networks related to SLC6A4 promoter methylation (N=74 healthy
      individuals). The amygdalae were defined as seed regions given that resting state
      functional connectivity in this brain area is under serotonergic control and
      relates to a broad range of psychiatric phenotypes. We further used bisulfite
      pyrosequencing to analyze quantitative methylation at 83 CpG sites within a
      promoter-associated CpG island of SLC6A4 from blood-derived DNA samples. The
      major finding of this study indicates a positive relation of SLC6A4 promoter
      methylation and amygdaloid resting state functional coupling with key nodes of
      the salience network (SN) including the anterior insulae and the dorsal anterior
      cingulate cortices. Increased intra-network connectivity in the SN is thought to
      facilitate the detection and subsequent processing of potentially negative
      stimuli and reflects a core feature of psychopathology. As such, epigenetic
      changes within the SLC6A4 gene predict connectivity patterns in clinically and
      behaviorally relevant brain networks which may in turn convey increased disease
      susceptibility.

PMID- 26303979
TI  - Effect of a combined oral contraceptive on patency of arterial anastomosis in a
      female rat model.
AB  - BACKGROUND: Oral contraceptives, which may lead to thrombotic events, are widely
      used drugs by women in reproductive age, some of whom might need emergent or
      elective microsurgical intervention. This study was planned to investigate the
      effects of combined oral contraceptives (COC) on arterial anastomosis patency in
      female rat model. METHODS: A third generation COC (ethinyl estradiol and
      desogestrel) was used in this study. A total of 50 female Wistar albino rats were
      included. The rats were divided into two groups. Experimental group received 0.03
      mg ethinyl estradiol/0.15 mg desogestrel with gastric catheter for 20 days before
      the surgery. Afterward, the femoral arteries of all rats were divided and
      anastomosed. The patency of the anastomoses were assessed surgically (at 15 min,
      7th day) and radiologically with Doppler ultrasonography (at 3rd and 7th days).
      The samples were examined using light microscopy, scanning electron microscopy
      (SEM), and transmission electron microscopy (TEM). RESULTS: The early patency
      assessed in the 15th min showed arterial flow in all rats. But at the 7th day 68%
      of the anastomosis were patent in the COC group while 100% of the anastomosis
      were patent in the control group as demonstrated surgically and radiologically (P
      = 0.004). Microscopic examination showed an increase in cytoplasmic organelles
      and activation of endothelial cells in all rats in the experimental group that
      received COCs. CONCLUSION: The present study demonstrated the negative effects of
      the use of COCs on anastomosis patency in rats.

PMID- 26303980
TI  - Paraneoplastic Epidermolysis Bullosa Acquisita Associated with Thyroid Carcinoma.

PMID- 26303981
TI  - Growth performance, intestinal histology, and biochemical parameters of rainbow
      trout (Oncorhynchus mykiss) in response to dietary inclusion of heat-killed
      Gordonia bronchialis.

PMID- 26303982
TI  - Differential responses of Oryza sativa secondary metabolism to biotic
      interactions with cooperative, commensal and phytopathogenic bacteria.
AB  - MAIN CONCLUSION: Profiling of plant secondary metabolite allows to differentiate
      the different types of ecological interactions established between rice and
      bacteria. Rice responds to ecologically distinct bacteria by altering its content
      of flavonoids and hydroxycinnamic acid derivatives. Plants' growth and physiology
      are strongly influenced by the biotic interactions that plants establish with
      soil bacterial populations. Plants are able to sense and to respond accordingly
      to ecologically distinct bacteria, by inducing defense pathways against pathogens
      to prevent parasitic interactions, and by stimulating the growth of root
      associated beneficial or commensal bacteria through root exudation. Plant
      secondary metabolism is expected to play a major role in this control. However,
      secondary metabolite responses of a same plant to cooperative, commensal and
      deleterious bacteria have so far never been compared. The impact of the plant
      growth-promoting rhizobacteria (PGPR) Azospirillum lipoferum 4B on the secondary
      metabolite profiles of two Oryza sativa L. cultivars (Cigalon and Nipponbare) was
      compared to that of a rice pathogen Burkholderia glumae AU6208, the causing agent
      of bacterial panicle blight and of a commensal environmental bacteria Escherichia
      coli B6. Root and shoot rice extracts were analyzed by reversed-phase high
      performance liquid chromatography (RP-HPLC). Principal component analyses (PCAs)
      pinpointed discriminant secondary metabolites, which were characterized by mass
      spectrometry. Direct comparison of metabolic profiles evidenced that each
      bacterial ecological interaction induced distinct qualitative and quantitative
      modifications of rice secondary metabolism, by altering the content of numerous
      flavonoid compounds and hydroxycinnamic acid (HCA) derivatives. Secondary
      metabolism varied according to the cultivars and the interaction types,
      demonstrating the relevance of secondary metabolic profiling for studying plant
      bacteria biotic interactions.

PMID- 26303983
TI  - Photoprotection related to xanthophyll cycle pigments in epiphytic orchids
      acclimated at different light microenvironments in two tropical dry forests of
      the Yucatan Peninsula, Mexico.
AB  - MAIN CONCLUSION: Epiphytic orchids from dry forests of Yucatan show considerable
      photoprotective plasticity during the dry season, which depends on leaf
      morphology and host tree deciduousness. Nocturnal retention of antheraxanthin and
      zeaxanthin was detected for the first time in epiphytic orchids. In tropical dry
      forests, epiphytes experience dramatic changes in light intensity: photosynthetic
      photon flux density may be up to an order of magnitude higher in the dry season
      compared to the wet season. To address the seasonal changes of xanthophyll cycle
      (XC) pigments and photosynthesis that occur throughout the year, leaves of five
      epiphytic orchid species were studied during the early dry, dry and wet seasons
      in a deciduous and a semi-deciduous tropical forests at two vertical strata on
      the host trees (3.5 and 1.5 m height). Differences in XC pigment concentrations
      and photosynthesis (maximum quantum efficiency of photosystem II; F v/F m) were
      larger among seasons than between vertical strata in both forests. Antheraxanthin
      and zeaxanthin retention reflected the stressful conditions of the epiphytic
      microhabitat, and it is described here in epiphytes for the first time. During
      the dry season, both XC pigment concentrations and photosystem II heat
      dissipation of absorbed energy increased in orchids in the deciduous forest,
      while F v/F m and nocturnal acidification (DeltaH(+)) decreased, clearly as a
      response to excessive light and drought. Concentrations of XC pigments were
      higher than those in orchids with similar leaf shape in semi-deciduous forest.
      There, only Encyclia nematocaulon and Lophiaris oerstedii showed somewhat reduced
      F v/F m. No changes in DeltaH(+) and F v/F m were detected in Cohniella ascendens
      throughout the year. This species, which commonly grows in forests with less open
      canopies, showed leaf tilting that diminished light interception. Light
      conditions in the uppermost parts of the canopy probably limit the distribution
      of epiphytic orchids and the retention of zeaxanthin can help to cope with light
      and drought stress in these forests during the dry season.

PMID- 26303984
TI  - Effect of montelukast monotherapy on oxidative stress parameters and DNA damage
      in children with asthma.
AB  - BACKGROUND: There is ample knowledge reported in the literature about the role of
      oxidative stress in asthma pathogenesis. It is also known that the interaction of
      reactive oxygen species with DNA may result in DNA strand breaks. The aim of this
      study was to investigate if montelukast monotherapy affects oxidative stress and
      DNA damage parameters in a population of pediatric asthma patients. METHODS:
      Group I consisted of 31 newly diagnosed asthmatic patients not taking any
      medication, and group II consisted of 32 patients who had been treated with
      montelukast for at least 6 months. Forty healthy control subjects were also
      enrolled in the study. Plasma total oxidant status (TOS) and total antioxidant
      status (TAS) were measured to assess oxidative stress. DNA damage was assessed by
      means of alkaline comet assay. RESULTS: The patients in both group I and group II
      had statistically significant higher plasma TOS (13.1 +/- 4 and 11.1 +/- 4.1
      MUmol H2O2 equivalent/liter, respectively) and low TAS levels (1.4 +/- 0.5 and
      1.5 +/- 0.5 mmol Trolox equivalent/liter, respectively) compared with the control
      group (TOS: 6.3 +/- 3.5 MUmol H2O2 equivalent/liter and TAS: 2.7 +/- 0.6 mmol
      Trolox equivalent/liter; p < 0.05). DNA damage was 18.2 +/- 1.0 arbitrary units
      (a.u.) in group I, 16.7 +/- 8.2 a.u. in group II and 13.7 +/- 3.4 a.u. in the
      control group. There were statistically significant differences only between
      group I and the control group (p < 0.05). CONCLUSIONS: According to the findings,
      montelukast therapy makes only minimal but not statistically significant
      improvement in all TOS, TAS and DNA damage parameters.

PMID- 26303985
TI  - Effects of script training on the peer-to-peer communication of children with
      autism spectrum disorder.
AB  - A multiple baseline design across participants was used to demonstrate the
      effects of a script-training procedure on the peer-to-peer communication of 3
      children with autism spectrum disorder during group play with peers. Both
      scripted and unscripted initiations as well as responses to peers increased for
      all 3 participants. Stimulus generalization across novel toys, settings, and
      peers was observed. Novel unscripted initiations, responses, and appropriate
      changes in topics during peer-to-peer exchanges were analyzed by considering the
      cumulative frequency of these behaviors across phases of the study. Treatment
      gains were maintained during 4-week follow-up sessions. Results are discussed in
      terms of recommendations for practitioners, response variability, and potential
      future avenues of research. 

PMID- 26303986
TI  - Conservative surgery for multifocal/multicentric breast cancer.
AB  - Multifocal (MF) and multicentric (MC) breast cancer is regularly considered a
      relative contraindication for breast-conserving therapy (BCT). There are two
      reasons for this wide spread notion: However, we concur that if optimal
      'cytoreductive surgery' is achieved this will result in good local control (i.e.
      in-breast relapse <10% at 10 years). This can only be achieved on the basis of
      the right imaging, image guidance for non-palpable foci, and tumor free (invasive
      as well as ductal carcinoma in situ) margins after adequate pathological
      assessment. Surgery must then be followed by whole breast irradiation and
      systemic treatments as indicated by primary cancer biology. Careful planning and
      adaptive application of oncoplastic techniques will result in an optimal cosmetic
      results. The meticulous work of Roland Holland and coworkers(1) in the early
      1980's on whole breast specimen showed invasive foci at more then 2 cm distance
      from the invasive primary cancer in more then 40% of specimen. Although multiple
      tumor foci may occur in up to 60% of mastectomy specimens, equivalent survival
      outcomes were observed in prospective trials comparing BCT and mastectomy for
      clinically unifocal lesions, suggesting that the majority of these foci are not,
      or do not become, biologically relevant or clinically significant with
      appropriate treatment. As diagnostic tools advance, MF and MC tumors are more
      commonly diagnosed. Cancers that previously would have been classified as
      unifocal now can be detected as MF or MC. In addition, locoregional treatment
      modalities have improved significantly over the past decade. More recent studies
      reflect these advances in diagnosis and treatment. Studies evaluated staging MRI
      showed that up to 19% of woman with diagnosed breast cancer harbor a second
      malignant ipsilateral lesion. These findings should only have consequences when
      additional lesions are proven cancer. Multiple enhancing lesions on MRI are in
      itself not an indication for a mastectomy. The Z0011 trial and the AMAROS trial
      demonstrated a similar phenomenon for axillary treatment; less surgery does not
      necessarily lead to inferior local control or survival outcomes. Recent studies
      supplement the growing evidence that treatment of patients with MF/MC breast
      cancer with BCS, radiotherapy, and adjuvant systemic therapy can result in low
      rates of in-breast recurrence.

PMID- 26303987
TI  - Management of breast cancer in older and frail patients.
AB  - Almost 50% of breast cancer occurs in women over the age of 65 years. The
      incidence of non standard adjuvant treatment increases with age and this group
      are under represented in clinical trials. We discuss tools to aid patient
      selection and adjuvant treatments including surgery, radiotherapy and systemic
      therapies for this group of patients.

PMID- 26303988
TI  - Premenstrual syndrome.
AB  - INTRODUCTION: A woman has premenstrual syndrome (PMS) if she complains of
      recurrent psychological and/or physical symptoms occurring during the luteal
      phase of the menstrual cycle, and often resolving by the end of menstruation.
      Symptom severity can vary between women. Premenstrual symptoms occur in 95% of
      women of reproductive age. Severe, debilitating symptoms occur in about 5% of
      those women. There is no consensus on how symptom severity should be assessed for
      PMS, which has led to the use of a wide variety of symptom scores and scales,
      thus making it difficult to synthesise data on treatment efficacy. The cyclical
      nature of the condition also makes it difficult to conduct RCTs. METHODS AND
      OUTCOMES: We conducted a systematic overview, aiming to answer the following
      clinical question: What are the effects of continuous hormonal treatments in
      women with premenstrual syndrome? We searched: Medline, Embase, The Cochrane
      Library, and other important databases up to April 2014 (Clinical Evidence
      overviews are updated periodically; please check our website for the most up-to
      date version of this overview). RESULTS: At this update, searching of electronic
      databases retrieved 132 studies. After deduplication and removal of conference
      abstracts, 132 records were screened for inclusion in the overview. Appraisal of
      titles and abstracts led to the exclusion of 102 studies and the further review
      of 30 full publications. Of the 30 full articles evaluated, one systematic review
      and three RCTs were added to this overview. We performed a GRADE evaluation for
      three PICO combinations. CONCLUSIONS: In this systematic overview, we categorised
      the efficacy for three interventions based on information relating to the
      effectiveness and safety of continuous combined oral contraceptives, continuous
      transdermal estradiol, and continuous subcutaneous estradiol implants.

PMID- 26303989
TI  - Monodisperse Micro-Oil Droplets Stabilized by Polymerizable Phospholipid Coatings
      as Potential Drug Carriers.
AB  - There is a critical need to formulate stable micron-sized oil droplets as
      hydrophobic drug carriers for efficient drug encapsulation, long-term storage,
      and sustained drug release. Microfluidic methods were developed to maximize the
      stability of micron-sized, oil-in-water (o/w) emulsions for potential use in drug
      delivery, using doxorubicin-loaded triacetin oil as a model hydrophobic drug
      formulation. Initial experiments examined multiple flow conditions for the
      dispersed (oil) and continuous (liposome aqueous) phases in a microfluidic device
      to establish the parameters that influenced droplet size. These data were fit to
      a mathematical model from the literature and indicate that the droplet sizes
      formed are controlled by the ratio of flow rates and the height of the device
      channel, rather than the orifice size. Next, we investigated effects of o/w
      emulsion production methods on the stability of the droplets. The stability of
      o/w emulsion produced by microfluidic flow-focusing techniques was found to be
      much greater (5 h vs 1 h) than for emulsions produced by mechanical agitation
      (vortexing). The increased droplet stability was attributed to the uniform size
      and lipid distribution of droplets generated by flow-focusing. In contrast,
      vortexed populations consisted of a wide size distribution that resulted in a
      higher prevalence of Ostwald ripening. Finally, the effects of shell
      polymerization on stability were investigated by comparing oil droplets
      encapsulated by a photopolymerizable diacetylene lipid shell to those with a
      nonpolymerizable lipid shell. Shell polymerization was found to significantly
      enhance stability against dissolution for flow-focused oil droplets but did not
      significantly affect the stability of vortexed droplets. Overall, results of
      these experiments show that flow-focusing is a promising technique for generating
      tunable, stable, monodisperse oil droplet emulsions, with potential applications
      for controlled delivery of hydrophobic drug formulations. 

PMID- 26303990
TI  - Gestational weight gain and body mass indexes have an impact on the outcomes of
      diabetic mothers and infants.
AB  - AIM: This study evaluated mothers with diabetes to determine whether prepregnancy
      body mass index (BMI), BMI on delivery or gestational weight gain (GWG) had the
      greatest impact on maternal and neonatal outcomes. METHODS: We retrospectively
      examined the medical charts of 634 full-term infants born to mothers with
      gestational diabetes mellitus not requiring insulin (n = 476), gestational
      diabetes mellitus requiring insulin (n = 140) and insulin-dependent diabetes
      mellitus (n = 18). Data regarding maternal BMI before pregnancy and on delivery
      were recorded, as well as maternal and neonatal complications. RESULTS: Infants
      born to women who gained more than the recommended weight during pregnancy had
      higher birthweights, higher rates of meconium-stained amniotic fluid and neonatal
      hypoglycaemia. Using logistic regression, Caesarean section delivery was
      predicted by gestational diabetes requiring insulin, with an odds ratio (OR) of
      1.76, maternal hypertension (OR 2.4), infants born large for gestational age (OR
      2.78) and maternal BMI >= 30 on delivery (OR 1.06). Neonatal complications were
      predicted by maternal insulin-dependent diabetes (OR 5.21), lower gestational age
      (OR 0.8) and GWG above the recommended amount (OR 1.56). CONCLUSION: Women with
      diabetes should be made aware that higher GWG can lead to Caesarean section
      delivery, infant macrosomia and other neonatal complications.

PMID- 26303992
TI  - Adherence to Ivacaftor is suboptimal.

PMID- 26303991
TI  - Anti-Pseudomonas aeruginosa IgY antibodies augment bacterial clearance in a
      murine pneumonia model.
AB  - BACKGROUND: Oral prophylactic therapy by gargling with pathogen-specific egg yolk
      immunoglobulins (IgY) may reduce the initial airway colonization with Pseudomonas
      aeruginosa in cystic fibrosis (CF) patients. IgY antibodies impart passive
      immunization and we investigated the effects of anti-P. aeruginosa IgY antibodies
      on bacterial eradication in a murine pneumonia model. METHODS: P. aeruginosa
      pneumonia was established in Balb/c mice and the effects of prophylactic IgY
      administration on lung bacteriology, clinical parameters and subsequent
      inflammation were compared to controls. RESULTS: Prophylactic administration of
      IgY antibodies targeting P. aeruginosa significantly reduced the bacterial burden
      by 2-log 24h post-infection compared to controls and was accompanied by
      significantly reduced clinical symptom scores and successive inflammatory
      cytokine profile indicative of diminished lung inflammation. CONCLUSIONS: Passive
      immunization by anti-P. aeruginosa IgY therapy facilitates promptly bacterial
      clearance and moderates inflammation in P. aeruginosa lung infection and may
      serve as an adjunct to antibiotics in reducing early colonization.

PMID- 26303993
TI  - Loss of B cell regulatory function is associated with delayed healing in patients
      with tibia fracture.
AB  - The process of bone regeneration after fracture is a complex and well
      orchestrated process usually requiring 3-12 weeks. A subset of patients, however,
      exhibit delayed healing time and even incomplete restoration of the normal bone
      structure. Although the precise mechanism is unknown, studies have shown that
      smurf1 may play a role during the process. Here, we sought to determine the
      involvement of the immune system in impaired bone healing. We found that
      immediately after fracture, the B-cell composition was shifted toward increased
      frequency of plasmablasts and decreased frequency of naive B cells, reflecting
      higher inflammatory status. The percentage of CD19(+) CD24(+) CD38(+) regulatory
      B cells was also upregulated in response to bone fracture. The production of IL
      10, a pivotal cytokine in regulatory B-cell function, was upregulated in all
      patients. Interestingly, the increase in IL-10 production was only sustained
      throughout the healing course in normal healing patients but not in delayed
      healing patients. Rather, delayed healing patients downregulated B-cell IL-10
      secretion early and had reduced level of regulatory B-cell activity. Together,
      these data revealed a role of regulatory B cells in the endogenous bone
      regeneration process and an alternation in B-cell-mediated regulation in delayed
      healing patients.

PMID- 26303994
TI  - Aggravated Liver Injury but Attenuated Inflammation in PTPRO-Deficient Mice
      Following LPS/D-GaIN Induced Fulminant Hepatitis.
AB  - BACKGROUND/AIMS: Critical roles of PTPRO and TLR4 have been implicated in
      hepatocellular carcinoma. However, little is known about their modifying effects
      on inflammation-related diseases in liver, particularly fulminant hepatitis (FH).
      We aim to investigate the potential role of PTPRO and its interaction with TLR4
      in LPS/D-GaIN induced FH. METHODS: A LPS/D-GaIN induced mouse FH model was used.
      RAW264.7 cells were transfected with PTPRO over-expressed lentiviral plasmids for
      further investigation. RESULTS: The mortality of PTPRO KO mice is higher than WT
      mice after LPS/D-GaIN administration. Aggravated liver injury was demonstrated by
      increased level of serous ALT and AST and numerous hepatic cells death in PTPRO
      KO mice following LPS/D-GaIN administration. Interestingly, inflammation was
      attenuated in PTPRO-deficient mice following LPS/D-GaIN administration, which was
      suggested by decreased inflammatory cytokines (TNF-alpha, IFN-gamma, IL-1beta, IL
      6, IL-17A and IL-12) and cells infiltrating into spleen (CD3(+)IFN-gamma(+)
      cells, CD3(+)TNF-alpha(+) cells, F4/80(+)/TLR4(+) cells). A feedback regulation
      between PTPRO and TLR4 dependent on NF-kappaB signaling pathway was demonstrated
      in vivo and in vitro. CONCLUSION: PTPRO plays an important role in FH by
      interacting with TLR4. The crosstalk between PTPRO and TLR4 is a novel bridge
      linking innate immune and adaptive immune in acute liver injury.

PMID- 26303995
TI  - Turner's syndrome: is there a risk of widespread vascular abnormalities?

PMID- 26303996
TI  - Toward More GI-Friendly Anti-Inflammatory Medications.
AB  - OPINION STATEMENT: Despite the introduction 20-30 years ago of potent inhibitors
      of gastric acid secretion and anti-inflammatory drugs that preferentially inhibit
      cyclo-oxygenase (COX)-2, the GI adverse effects of nonsteroidal anti-inflammatory
      drugs (NSAIDs) remain a significant clinical concern and a considerable economic
      burden. Inhibitors of acid secretion and selective COX-2 inhibitors reduce damage
      only in the proximal GI tract (stomach and proximal duodenum), but NSAIDs produce
      injury and bleeding throughout the GI tract. The small intestinal damage caused
      by NSAIDs is common, difficult to diagnose, and there are no proven-effective
      preventative or curative therapies. There is also emerging evidence that proton
      pump inhibitors (PPIs) and histamine H2-receptor antagonists (H2RAs) exacerbate
      NSAID-induced small intestinal injury. A new approach to solve this clinical
      problem is to deliver an endogenous, cytoprotective "rescue molecule" together
      with a COX inhibitor. Hydrogen sulfide (H2S) is a naturally produced, potent
      protective agent in the GI tract. H2S-releasing NSAIDs have been synthesized and
      extensively tested in laboratory animals and humans. They exhibit improved anti
      inflammatory activity over the parent NSAID, while causing negligible damage in
      the GI tract.

PMID- 26303999
TI  - Torsional malalignment, how much significant in the trochanteric fractures?
AB  - OBJECTIVES: The rotational alignment is definitely important in the long bones
      such as tibias and femurs. We also predict the importance of rotational alignment
      in the trochanteric fractures. So we measured torsional malalignment in
      trochanteric fracture and anlaysed their risk factors and their clinical
      significance. METHODS: A total of 109 inpatients who had undergone internal
      fixation following trochanteric fracture and a postoperative pelvic CT scan
      between 2008 and 2013, with at least one year follow-up, were selected. Factors
      that affect torsional malalignment, such as age, gender, fracture stability,
      injured area, operative time, time of surgery after admission, and ASA status,
      were investigated. Factors that affect the patients' clinical results in
      malrotation, including ambulation time after surgery, postoperative complication
      rates, pain assessment of VAS one year postoperatively and Koval score, were also
      investigated. RESULTS: Of the 109 subjects, torsional malalignment was observed
      in 28 (25.7%) subjects with a mean torsional malalignment angle of 20.7 degrees 
      (range: -31.2 degrees  to 27.1 degrees ). Torsional malalignment risk factors
      were fracture stability (p=0.021) and operative time (p=0.043). In terms of the
      time to ambulation after surgery, the postoperative complication rates, and the
      VAS and Koval scores at one year postoperatively, no statistically significant
      difference was observed between the torsional malalignment patients and the non
      deformity patients. CONCLUSIONS: In this study, 25.7% of the patients who had
      undergone internal fixation following trochanteric fracture experienced torsional
      malalignment. Major factors of the torsional malalignment were an unstable
      fracture and the consequent delay in the operative time. But the torsional
      malalignment was deemed to have no effect on clinical results.

PMID- 26304000
TI  - Surgical management of infected non-unions: An update.
AB  - Infected non-union is a devastating complication post fracture fixation. While
      its incidence is small, its management is lengthy, challenging and costly.
      Complex reconstruction surgery is often required with unpredictable outcomes
      despite the significant advances that have been made in diagnostics, surgical
      techniques and antibiotic protocols. In this article we present recent approaches
      to the surgical treatment of this condition. 

PMID- 26304001
TI  - Use of a Nancy nail to remove a broken intramedullary nail: A technical note.
AB  - Intramedullary (IM) nailing is a standard surgical technique for treating long
      bone diaphyseal fractures. However, one complication is breakage of the IM nail.
      Many methods have been reported for removing broken nails. We devised another
      technique, using a Nancy nail, for removing a broken IM nail and report on the
      surgical technique and a case involving the use of our method. 

PMID- 26303997
TI  - Empagliflozin/linagliptin single-tablet combination: first-in-class treatment
      option.
AB  - BACKGROUND: The availability of a dual sodium glucose co-transporter 2/dipeptidyl
      peptidase-4 inhibitor combination in a single-tablet combination (STC) represents
      a new therapeutic option for patients with type 2 diabetes.
      Empagliflozin/linagliptin STC has been recently approved by the US Food and Drug
      Administration for the treatment of type 2 diabetes mellitus (T2DM). AIM: The aim
      of this study was to describe the latest clinical evidence on the efficacy and
      safety profiles of empagliflozin/linagliptin STCs in comparison with the
      individual components. Juxtaposition of the STC with dapagliflozin/saxagliptin
      combination was also presented. RESULTS: Empagliflozin/linagliptin STC given as
      initial therapy or on metformin background lowered mean glycated haemoglobin
      (HbA1c) by approximately 1.1% (mean baseline HbA1c, 8.0%). Furthermore, the STC
      reduced mean body weight by 2.0-3.0 kg from baseline. With the STC treatment, no
      confirmed incidents of hypoglycaemia were reported in drug-naive patients; in
      patients taking metformin hypoglycaemia occurred at low rates which were
      comparable with monotherapy. Use of STCs in the treatment of T2DM can simplify
      drug dosing regimen, reduce pill burden and increase treatment adherence.
      Empagliflozin/linagliptin STC is a combination that offers potential additional
      benefits such as body weight loss and moderate reductions in blood pressure,
      without increasing risk of hypoglycaemia. CONCLUSION: Empagliflozin/linagliptin
      STC appears to be a rational choice for a wide range of patients in need of
      multiple agents for controlling hyperglycaemia. The STC should be particularly
      useful in patients in whom hypoglycaemia, weight gain and treatment adherence are
      of concern.

PMID- 26304002
TI  - Inter-rater agreement on assessment of outcome within a trauma registry.
AB  - INTRODUCTION: To better evaluate the degree of ongoing disability in trauma
      patients, it has been recommended that trauma registries introduce routine long
      term outcome measurement. One of the measures recommended for use is the Extended
      Glasgow Outcome Scale (GOS-E). However, few registries have adopted this measure
      and further research is required to determine its reliability with trauma
      populations. This study aimed to evaluate the inter-rater agreement of GOS-E
      scoring between an expert rater and trauma registry follow-up staff with a sample
      of detailed trauma case scenarios. METHODS: Sixteen trauma registry telephone
      interviewers participated in the study. They were provided with a written summary
      of 15 theoretical adult trauma cases covering a spectrum of disability and asked
      to rate each case using the structured GOS-E interview. Their ratings were
      compared with those of an expert rater in order to calculate the inter-rater
      agreement for each individual rater-expert rater pair. Agreement was reported as
      the percentage of agreement, the kappa statistic, and weighted kappa. A multi
      rater kappa value was also calculated for agreement between the 16 raters.
      RESULTS: Across the 15 cases, the percentage of agreement between individual
      raters and the expert ranged from 63% to 100%. Across the 16 raters, the
      percentage of agreement with the expert rater ranged from 73-100% (mean=90%).
      Kappa values ranged from 0.65 to 1.00 across raters (mean=0.86) and weighted
      kappa values ranged from 0.73 to 1.00 (mean=0.89) The multi-rater kappa value was
      0.78 (95% CI: 0.66, 0.89). CONCLUSIONS: Sixteen follow-up staff achieved
      'substantial' to 'almost perfect' agreement with an expert rater using the GOS-E
      outcome measure to score 15 sample trauma cases. The results of this study lend
      support to the use of the GOS-E within trauma populations and highlight the
      importance of ongoing training where multiple raters are involved to ensure
      reliable outcome reporting. It is also recommended that the structured GOS-E
      interview guide be used to achieve better agreement between raters. Ensuring the
      reliability of trauma outcome scores will enable more accurate evaluation of
      patient outcomes, and ultimately, more targeted trauma care.

PMID- 26304003
TI  - An Internationally Comparative Study of Immigration and Adolescent Emotional and
      Behavioral Problems: Effects of Generation and Gender.
AB  - PURPOSE: Although the potential consequences of immigration for adolescent
      problem behaviors have been addressed in many former studies, internationally
      comparative research is scarce. This study investigated the impact of immigration
      on four indicators of adolescents' emotional and behavioral problems in 10
      countries, taking into account gender and immigrant generation as moderating
      factors. METHODS: Analyses were based on data from 11-, 13-, and 15-year-old
      adolescents participating in the Health Behavior in School-aged Children study in
      Denmark, Germany, Greece, Iceland, Ireland, Italy, the Netherlands, Spain, the
      United States, and Wales (total N = 53,218). RESULTS: Both first- and second
      generation immigrant adolescents reported higher levels of physical fighting and
      bullying and a lower life satisfaction than native adolescents, whereas second
      generation immigrant adolescents reported more psychosomatic symptoms than native
      adolescents. Effect sizes varied considerable for the different outcomes, and
      similar effects were found for first- and second-generation immigrant
      adolescents. Differences in these indicators of emotional and behavioral problems
      between immigrant and native adolescents did not vary significantly with the
      receiving country. With two exceptions, effects of immigrant status were similar
      for boys and girls. Although no differences in psychosomatic symptoms were found
      between first-generation immigrant and native girls, first-generation immigrant
      boys reported less psychosomatic symptoms than native boys. Furthermore, both
      second-generation immigrant boys and girls reported higher levels of physical
      fighting than their native peers, but differences were more pronounced for boys
      than for girls. CONCLUSIONS: Overall, the results of this study support a risk
      perspective on the impact of immigration on adolescent problem behaviors.

PMID- 26304006
TI  - Prostate cancer: Of margins and men--do surgical margins matter?

PMID- 26304009
TI  - Prostate cancer: A simplified prostate cancer grading system.

PMID- 26304010
TI  - Infection: UPEC subverts endosomal recycling by modulating Rab35.

PMID- 26304011
TI  - Morpho-physiological evaluation of tomato genotypes under high temperature stress
      conditions.
AB  - BACKGROUND: Tomato (Solanum lycopersicum L.) is an important but heat-sensitive
      vegetable crop. The losses in tomato production associated with heat stress are
      aggravating further under a global warming scenario. The present study was
      designed to investigate the comparative performance of tomato genotypes under
      high temperature stress. Tomato genotypes (191) were exposed to the controlled
      conditions of high temperature (40/32  degrees C day/night temperature).
      Different morphological (shoot length, root length, shoot fresh weight, root
      fresh weight, shoot dry weight, root dry weight and number of leaves),
      physiological (photosynthetic rate, transpiration rate, water use efficiency,
      stomatal conductance to water, sub-stomatal CO2 and leaf temperature) and SPAD
      value (chlorophyll content) were recorded to check the diversity among genotypes
      against heat stress. RESULTS: All the genotypes showed a significantly variable
      response in almost all the attributes under high-temperature conditions.
      Correlation among the variables provided a clear understanding of the phenomena
      involved. Based on all the attributes studied, genotypes L00090 and L00091 were
      found to be the most heat tolerant compared to other genotypes, whereas CLN1462A
      and CLN 1466E were found to be comparatively sensitive. CONCLUSION: It was
      concluded that the studied attributes were genotype dependent, and significant
      diverse performance was noted. The findings of this study pave the way towards
      the selection of tolerant genotypes, not only for use under high-temperature
      conditions but also to employ them in breeding programs to produce heat-tolerant
      hybrids. (c) 2015 Society of Chemical Industry.

PMID- 26304013
TI  - Evaluation of home respiratory therapy delivered to patients in the Ministry of
      Health's Home Medical Program (HMP) and administered through the Madinah HMP
      Center, Kingdom of Saudi Arabia, 2013.
AB  - This was an evaluation of home respiratory therapy (HRT) services administered
      through the Madinah Home Medical Program (MHMP) Center of the Ministry of Health
      (MoH), Kingdom of Saudi Arabia (KSA). Using a retrospective design and
      descriptive analyses, we analyzed 83 patient records for the clinical care
      received, outcomes, and patient satisfaction. We also assessed a subset from an
      economic perspective. Demographically, 72% were >60 years of age, 80% were
      female, and 90% were Saudi. Asthma accounted for 34% of the diagnosed respiratory
      diseases, followed by chronic obstructive pulmonary disease (11%). Most patients
      (71%) required two or three respiratory modalities: 94% used oxygen therapy and
      14% were on mechanical ventilation. A full 90% of HMP patients expressed a high
      level of satisfaction with the HMP overall care, and 43% saw an improvement in
      their condition. The MHMP lowered healthcare costs for HRT-receiving patients by
      decreasing the frequency of emergency room (ER) and outpatient visits by 50.8%
      from 59 to 30 visits. HRT administered through the MHMP Center improved clinical
      outcomes and increased patient satisfaction while reducing hospital utilization
      and associated costs. A prospective study is recommended to assess HMP services
      in comparison with hospitalization.

PMID- 26304012
TI  - A repeat sequence domain of the ring-exported protein-1 of Plasmodium falciparum
      controls export machinery architecture and virulence protein trafficking.
AB  - The malaria parasite Plasmodium falciparum dramatically remodels its host red
      blood cell to enhance its own survival, using a secretory membrane system that it
      establishes outside its own cell. Cisternal organelles, called Maurer's clefts,
      act as a staging point for the forward trafficking of virulence proteins to the
      red blood cell (RBC) membrane. The Ring-EXported Protein-1 (REX1) is a Maurer's
      cleft resident protein. We show that inducible knockdown of REX1 causes stacking
      of Maurer's cleft cisternae without disrupting the organization of the knob
      associated histidine-rich protein at the RBC membrane. Genetic dissection of the
      REX1 sequence shows that loss of a repeat sequence domain results in the
      formation of giant Maurer's cleft stacks. The stacked Maurer's clefts are
      decorated with tether-like structures and retain the ability to dock onto the RBC
      membrane skeleton. The REX1 mutant parasites show deficient export of the major
      virulence protein, PfEMP1, to the red blood cell surface and markedly reduced
      binding to the endothelial cell receptor, CD36. REX1 is predicted to form a
      largely alpha-helical structure, with a repetitive charge pattern in the repeat
      sequence domain, providing potential insights into the role of REX1 in Maurer's
      cleft sculpting. 

PMID- 26304014
TI  - First molecular identification of Babesia gibsoni in dogs from Slovakia, central
      Europe.
AB  - Canine babesiosis is a severe and potentially life threatening infection. In
      Europe, Babesia canis is considered to be the most common species responsible for
      the disease. We report two cases of babesiosis caused by Babesia gibsoni. The
      polymerase chain reaction, restriction fragment length polymorphism analysis and
      further sequencing of 18S rRNA gene fragments from blood samples of both dogs
      revealed the identity of isolates with B. gibsoni genotypes from other dogs
      worldwide. This species was previously not known to infect dogs in Slovakia. It
      is resistant to traditional anti-babesial therapy. Therefore, correct diagnosis
      is crucial for the successful treatment, especially in dogs with hemolytic anemia
      and febrile conditions. 

PMID- 26304015
TI  - Efficacy of on-demand treatment in reducing morbidity in patients with hereditary
      angioedema due to C1 inhibitor deficiency.
AB  - BACKGROUND: Angioedema due to hereditary deficiency of C1 inhibitor causes
      temporarily disability. Guidelines recommend early on-demand treatment of attacks
      to reduce morbidity. In this prospective observational study, we evaluated the
      efficacy of on-demand approach. METHODS: From January 2009 to August 2014, data
      on attacks and treatments were collected from 227 patients from our centre in
      Milan. RESULTS: A total of 4244 attacks were reported; 50% were treated with
      approved therapies (pdC1-INH or icatibant), 15% were with tranexamic acid, and
      35% were not treated. Attack locations were peripheral cutaneous (46%), abdominal
      (34%), multiple (12%), facial (5%) and laryngeal (3%). Attack severities were
      moderate (48%), mild (28%) and severe (24%). Median attack duration (data
      available for 2393 attacks) with approved therapies was 10 h, significantly
      shorter than without treatment (45 h) or with tranexamic acid (38 h). Most of the
      treatments were self-administered: 93% with icatibant and 59% with pd-C1-INH.
      Median attack duration with icatibant was 8 and 11.5 h with pd-C1 INH. Median
      time from onset of symptoms to drug administration was 1 h with icatibant and 2 h
      with pd-C1INH and median time from drug administration to complete resolution was
      5.5 and 8 h, respectively. Second treatment was required in 12.7% of icatibant
      treated attacks and in 1.9% of pdC1-INH-treated attacks. CONCLUSION: This study
      provides evidence that on-demand treatment is effective in reducing disease
      related morbidity. The use of on-demand treatment in Italy has increased up to
      50% of attacks in the last years, reflecting a better adherence to international
      guidelines.

PMID- 26304016
TI  - Octupolar (C3 and S4) Symmetric Cyclized Indole Derivatives: Syntheses,
      Structures, and NLO Properties.
AB  - Several cyclized indole derivatives have been synthesized, and their structures
      been determined. The C3-symmetric single-chiral N-phenyltriindole (Tr-Ph3)
      crystallized in the P1 space group, and the S4-symmetric saddle-like tetraindole
      (TTr) crystallized in the I4 space group. The Tr-Ph3 and TTr crystals exhibit
      remarkable powder SHG intensities 5 and 11 times that of KH2PO4 (KDP),
      respectively. TTr is a useful octupolar core to build S4-symmetric molecules and
      crystals for second-NLO materials. 

PMID- 26304017
TI  - Does group size have an impact on welfare indicators in fattening pigs?
AB  - Production systems for fattening pigs have been characterized over the last 2
      decades by rising farm sizes coupled with increasing group sizes. These
      developments resulted in a serious public discussion regarding animal welfare and
      health in these intensive production systems. Even though large farm and group
      sizes came under severe criticism, it is still unknown whether these factors
      indeed negatively affect animal welfare. Therefore, the aim of this study was to
      assess the effect of group size (30 pigs/pen) on various animal-based measures of
      the Welfare Quality((r)) protocol for growing pigs under conventional fattening
      conditions. A total of 60 conventional pig fattening farms with different group
      sizes in Germany were included. Moderate bursitis (35%) was found as the most
      prevalent indicator of welfare-related problems, while its prevalence increased
      with age during the fattening period. However, differences between group sizes
      were not detected (P>0.05). The prevalence of moderately soiled bodies increased
      from 9.7% at the start to 14.2% at the end of the fattening period, whereas large
      pens showed a higher prevalence (15.8%) than small pens (10.4%; P<0.05). With
      increasing group size, the incidence of moderate wounds with 8.5% and 11.3% in
      small- and medium-sized pens, respectively, was lower (P<0.05) than in large
      sized ones (16.3%). Contrary to bursitis and dirtiness, its prevalence decreased
      during the fattening period. Moderate manure was less often found in pigs fed by
      a dry feeder than in those fed by a liquid feeding system (P<0.05). The human
      animal relationship was improved in large in comparison to small groups. On the
      contrary, negative social behaviour was found more often in large groups.
      Exploration of enrichment material decreased with increasing live weight. Given
      that all animals were tail-docked, tail biting was observed at a very low rate of
      1.9%. In conclusion, the results indicate that BW and feeding system are
      determining factors for the welfare status, while group size was not proved to
      affect the welfare level under the studied conditions of pig fattening.

PMID- 26304018
TI  - Photolichenoid papules within vitiligo induced by narrowband UVB phototherapy.

PMID- 26304020
TI  - Differential gene expression in the endometrium reveals cytoskeletal and
      immunological genes in lactating dairy cows genetically divergent for fertility
      traits.
AB  - Profitable milk production in dairy cows requires good reproductive performance.
      Calving interval is a trait used to measure reproductive efficiency. Herein we
      used a novel lactating Holstein cow model of fertility that displayed genetic and
      phenotypic divergence in calving interval, a trait used to define reproductive
      performance using a national breeding index in Ireland. Cows had similar genetic
      merit for milk production traits, but either very good genetic merit for
      fertility (Fert+; n=7) or very poor genetic merit for fertility (Fert-; n=6). We
      tested the hypothesis that Fert+ cows would have a corresponding detectable
      difference in endometrial gene expression compared with the Fert- cows. To do
      this, we sequenced the transcriptome of endometrial biopsies collected on Day 7
      of the oestrous cycle (non-pregnant). This is an important stage for uterine
      remodelling and initiation of histotroph secretion. Significant differential
      expression (false discovery rate-adjusted P<0.1) of 403 genes between Fert+ and
      Fert- cows was found. A novel network-based functional analysis highlighted 123
      genes from three physiologically relevant networks of the endometrium: (1) actin
      and cytoskeletal components; (2) immune function; and (3) ion transportation. In
      particular, our results indicate an overall downregulation of inflammation
      related genes and an upregulation of multiple ion transporters and gated-voltage
      channels and cytoskeletal genes in Fert+ cows. These three topics, which are
      discussed in terms of the uterus and in the context of fertility, provide
      molecular evidence for an association between gene expression in the uterine
      environment and genetic merit for fertility in dairy cows.

PMID- 26304019
TI  - Nuclear Localization of the DNA Repair Scaffold XRCC1: Uncovering the Functional
      Role of a Bipartite NLS.
AB  - We have characterized the nuclear localization signal (NLS) of XRCC1 structurally
      using X-ray crystallography and functionally using fluorescence imaging.
      Crystallography and binding studies confirm the bipartite nature of the XRCC1 NLS
      interaction with Importin alpha (Impalpha) in which the major and minor binding
      motifs are separated by >20 residues, and resolve previous inconsistent
      determinations. Binding studies of peptides corresponding to the bipartite NLS,
      as well as its major and minor binding motifs, to both wild-type and mutated
      forms of Impalpha reveal pronounced cooperative binding behavior that is
      generated by the proximity effect of the tethered major and minor motifs of the
      NLS. The cooperativity stems from the increased local concentration of the second
      motif near its cognate binding site that is a consequence of the stepwise binding
      behavior of the bipartite NLS. We predict that the stepwise dissociation of the
      NLS from Impalpha facilitates unloading by providing a partially complexed
      intermediate that is available for competitive binding by Nup50 or the Importin
      beta binding domain. This behavior provides a basis for meeting the intrinsically
      conflicting high affinity and high flux requirements of an efficient nuclear
      transport system. 

PMID- 26304021
TI  - Enhancing the care of women with rheumatic diseases during pregnancy: challenges
      and unmet needs in the Middle East.
AB  - Pregnancy in women with rheumatic disorders is known to be associated with risks
      for both the mother and fetus; however, these risks can be minimized with proper
      planning and careful management of the disease. In the Middle East, there are
      specific cultural challenges that may have a negative impact on the care that
      women with rheumatic disorders receive. There is a need for cross-collaboration
      between specialist physicians, improved awareness of rheumatic disorders among
      the general public and more open discussion with patients about the potential
      complications of pregnancy. Women in the region are often unwilling to discuss
      their disease with their partner and are even less likely to seek advice
      regarding family planning from their physician. The objective of this review is
      to highlight the specific challenges of pregnancy management and to discuss why
      establishing specialist pregnancy clinics for women with rheumatic disorders
      could be an effective solution. Such clinics can provide high quality care
      before, during and after pregnancy as shown in several European and US centers.
      Additionally, such clinics could be useful for the collection of pregnancy
      outcomes data from the Middle East, which may currently be lacking in the region,
      in order to highlight where further improvements can be made. With specialist
      care and analysis of pregnancy outcomes, the standard of care for women with
      rheumatic disorders in this area could be significantly improved. 

PMID- 26304022
TI  - ACCURACY OF RADIOGRAPHIC DETECTION OF THE CRANIAL MARGIN OF THE DORSAL LAMINA OF
      THE CANINE SACRUM.
AB  - An elongated sacral lamina has been described as one of the contributing factors
      for dogs with cauda equina syndrome due to degenerative lumbosacral stenosis
      (DLSS); however, published evidence is lacking on the accuracy of radiographic
      screening for the presence of this lesion. Objectives of this prospective, cross
      sectional cadaver study were to describe the accuracy and repeatability of
      detection of the cranial sacral lamina margin on plain lateral radiographs of the
      lumbosacral junction in dogs. Twenty-five medium and large breed canine cadavers
      were radiographed before and after placement of a radiopaque hook in the cranial
      margin of the sacral lamina. Three independent evaluators placed digital markers
      at the perceived margin on preinterventional radiographs. The distance from
      perceived location to the true location on postinterventional radiographs was
      recorded for each dog and observer. A discordance threshold (distance between
      perceived and actual margin) of 1.5 mm was subjectively defined as clinically
      relevant. The three evaluators demonstrated good repeatability, although the
      accuracy for margin detection was only fair (mean discordance 1.7 mm). Evaluators
      demonstrated greater accuracy in identifying the landmark in juveniles (1.4 mm)
      vs. adults (1.8 mm; P < 0.01). Results of this study indicated that observer
      repeatability is good and accuracy is fair for correctly identifying the
      radiographic cranial margin of the sacral lamina in dogs. This should be taken
      into consideration when interpreting elongation of the sacral lamina in
      radiographs of dogs with suspected DLSS, especially adults. 

PMID- 26304023
TI  - Viral metagenomics in drug-naive, first-onset schizophrenia patients with
      prominent negative symptoms.
AB  - Although several studies suggest a virus or (endogenous) retrovirus involvement
      at the time of onset of schizophrenia, the unequivocal identification of one or
      more infectious agents, by means of an undirected catch-all technique, has never
      been conducted. In this study VIDISCA, a virus discovery method, was used in
      combination with Roche-454 high-throughput sequencing as a tool to determine the
      possible presence of viruses (known or unknown) in blood of first-onset drugs
      naive schizophrenic patients with prominent negative symptoms. Two viruses (the
      Anellovirus Torque Teno virus and GB virus C) were detected. Both viruses are
      commonly found in healthy individuals and no clear link with disease was ever
      established. Viruses from the family Anelloviridae were also identified in the
      control population (4.8%). Besides, one patient sample was positive for human
      endogenous retroviruses type K (HML-2) RNA but no specific predominant strain was
      detected, instead 119 different variants were found. In conclusion, these
      findings indicate no evidence for viral or endogenous retroviral involvement in
      sera at the time of onset of schizophrenia. 

PMID- 26304024
TI  - A case-control study of the association between DARPP-32 gene polymorphisms and
      alcohol dependence in Chinese Han subjects.

PMID- 26304025
TI  - Immunopathologic Changes in the Thymus of Calves Pre-infected with BVDV and
      Challenged with BHV-1.
AB  - The aim of this work was to investigate the effect of pre-infection with bovine
      viral diarrhoea virus (BVDV) on thymus immune cells from calves challenged with
      bovine herpesvirus 1 (BHV-1). Twelve Friesian calves, aged 8 to 9 months, were
      inoculated with non-cytopathic BVDV-1. Ten of them were subsequently challenged
      with BHV-1 and euthanized in batches of two at 1, 2, 4, 7 or 14 dpi with BHV-1.
      The other two calves were euthanized prior to the second inoculation and were
      used as BVDV-infected controls. A further 10 calves were inoculated solely with
      BHV-1 and euthanized at the same time points. Two calves were not inoculated with
      any agent and were used as negative controls. Quantitative changes in immune
      cells were evaluated with immunohistochemical methods to compare coinfected
      calves and calves challenged only with BHV-1. The results of this study pointed
      out BVDV as responsible for the thymic lesions observed in the experiment as well
      as for the majority of immunopathologic changes, including a downregulation of
      Foxp3 lymphocytes and TGFbeta, which reverted as BVDV was cleared, and an
      overexpression of medullary CD8+ T cells. However, despite not inducing evident
      lesions in the thymus, BHV-1 seemed to prompt some immune alterations.
      Collectively, these data contribute to the knowledge on the immunopathologic
      alterations of the thymus during BVDV infections, and its importance in the
      development of secondary infections.

PMID- 26304026
TI  - Mother's but not father's education predicts general fluid intelligence in
      emerging adulthood: Behavioral and neuroanatomical evidence.
AB  - Lower parental education impairs cognitive abilities of their offspring such as
      general fluid intelligence dependent on the prefrontal cortex (PFC), but the
      independent contribution of mother's and father's education is unknown. We used
      an individual difference approach to test whether mother's and father's education
      independently affected general fluid intelligence in emerging adulthood at both
      the behavioral and neural level. Behaviorally, mother's but not father's
      education accounted for unique variance in general fluid intelligence in emerging
      adulthood (assessed by the Raven's advanced progressive matrices). Neurally, the
      whole-brain correlation analysis revealed that the regional gray matter volume
      (rGMV) in the medial PFC was related to both mother's education and general fluid
      intelligence but not father's education. Furthermore, after controlling for
      mother's education, the association between general fluid intelligence and the
      rGMV in medial PFC was no longer significant, indicating that mother's education
      plays an important role in influencing the structure of the medial PFC associated
      with general fluid intelligence. Taken together, our study provides the first
      behavioral and neural evidence that mother's education is a more important
      determinant of general cognitive ability in emerging adulthood than father's
      education.

PMID- 26304027
TI  - Flow-through anastomosis for both the artery and vein in leg free flap transfer.
AB  - OBJECTIVE: Free flap transfer is an essential part of limb-sparing surgery for
      leg sarcoma; however, this procedure is associated with a high failure rate. The
      aim of this study was to identify factors that contribute to microvascular
      compromise and flap failure for leg free flap transfer, while focusing on
      anastomotic techniques (end-to-end, end-to-side, and flow-through anastomoses).
      PATIENTS AND METHODS: Data from 56 consecutive patients who underwent leg free
      flap transfer after oncologic resection were retrospectively reviewed. Of these
      patients, flow-through anastomosis was performed with the artery in 29 and the
      vein in 24, whereas conventional techniques were performed in others. The
      variables contributing to microvascular compromise and flap failure were
      statistically analyzed. RESULTS: Venous thrombosis (four patients, 7.1%) was more
      frequent than arterial thrombosis (one patient, 1.8%) and (4 patients, 7.1%)
      resulted in flap loss. All anastomotic failures occurred in end-to-end
      anastomoses. All flow-through anastomoses achieved patency both for the artery
      and vein. No anastomotic failure or flap loss occurred in 22 flaps which were
      transferred with flow-through anastomosis for both the artery and vein. Flow
      through venous anastomosis tended to have a lower rate of microvascular
      compromise and flap loss than conventional techniques (P = 0.13 and 0.25,
      respectively). CONCLUSION: The key to successful leg free flap transfer is to
      prevent venous failure; thus, flow-through venous anastomosis may be a
      breakthrough solution. Preferential use of flow-through anastomosis for both the
      artery and vein can provide predictable results in leg free flap transfer.

PMID- 26304028
TI  - The association between circulating IGF1, IGFBP3, and calcium: results from
      NHANES III.
AB  - BACKGROUND: Despite mounting evidence linking both calcium and IGF1, there is a
      lack of studies investigating any association between circulating levels of IGF1
      and serum calcium. METHODS: Serum calcium, IGF1, and IGF-binding protein 3
      (IGFBP3) were measured for 5368 participants in NHANES III. We calculated
      multivariable-adjusted geometric means of serum concentrations of IGF1, IGFBP3,
      and IGF1/IGFBP3 by categories of calcium (lowest 5% (<1.16 mmol/l), mid 90%, and
      top 5% (>=1.31 mmol/l)). We also performed stratified analyses by sex, age,
      ethnicity, BMI, serum levels of vitamin D, and bone mineral density (BMD).
      RESULTS: Overall, we found that circulating calcium was positively associated
      with circulating levels of IGF1 and IGFBP3, but not their molar ratio (i.e.,
      geometric mean of IGF1 by increasing calcium categories: 237.63, 246.51, and
      264.22 ng/nl; Ptrend: 0.43; Pfirst vs third category: 0.01). In particular, these
      associations were observed in women, people aged <60, non-Hispanic whites, those
      with vitamin D levels above the mean, and those with low BMD. In contrast, there
      was an inverse association with the molar ratio for those with BMI >=30 kg/m(2).
      CONCLUSION: We found an overall positive association between circulating levels
      of IGF1 and IGFBP3 and serum calcium. However, stratification by potential effect
      modifiers did not support all suggested hypotheses. Our findings provide more
      insight into the interplay between calcium and IGF1, which in the future can be
      investigated in larger observational studies allowing for additional
      stratifications based on a combination of the different effect-modifiers
      investigated here.

PMID- 26304029
TI  - Electromechanical mapping of the left ventricle for stem cell injection in a
      patient with permanent atrial fibrillation.

PMID- 26304030
TI  - Rosacea: The Blessing of the Celts - An Approach to Pathogenesis Through
      Translational Research.
AB  - Increased expression of cathelicidin antimicrobial peptide (CAMP) is related to
      the pathogenesis of rosacea. CAMP plays a crucial role in antimicrobial defences,
      such as the killing of mycobacteria. CAMP gene expression is regulated by vitamin
      D-dependent (VDR) and vitamin D-independent (C/EBPalpha) transcription factors.
      VDR-dependent CAMP expression is sufficient during the summer months in Nordic
      countries, but insufficient during Nordic winters, due to low ultraviolet (UV)
      levels. Historically, the Celts may have overcome this geographical disadvantage
      of deficient CAMP production during the winter through an as-yet undefined
      acquired mutation that activates the alternative vitamin D-independent CAMP
      promoter C/EBPalpha. C/EBPalpha is the downstream transcription factor of Toll
      like receptor (TLR)-mediated innate immune reactions and endoplasmic reticulum
      (ER) stress responses. At the molecular level, all clinical trigger factors for
      rosacea can be regarded as ER stressors. A mutation-based upregulation of ER
      stress responsiveness in rosacea may thus explain patients' reduced threshold for
      ER stressors. It is notable that ER stress upregulates the potent lipid-mediator
      sphingosine-1-phosphate (S1P), which explains multiple pathological aberrations
      observed in rosacea skin. Enhanced ER stress/S1P signalling in rosacea appears to
      compensate for insufficient VDR-dependent CAMP expression, maintaining adequate
      CAMP levels during UV-deficient winter to combat life-threatening microbial
      infections, such as lupus vulgaris. Therefore, rosacea should not be considered
      as a disadvantage, but as evolution's blessing of the Celts which improved their
      survival. The concept presented here also explains the mechanism of Finsen's UV
      treatment of lupus vulgaris by UV- and ER stress-mediated upregulation of CAMP
      expression. Rosacea could therefore be described as the Celts' "inborn Finsen
      lamp". 

PMID- 26304031
TI  - Children with Autism Spectrum Disorders Make a Fruit Salad with Probo, the Social
      Robot: An Interaction Study.
AB  - Social robots are thought to be motivating tools in play tasks with children with
      autism spectrum disorders. Thirty children with autism were included using a
      repeated measurements design. It was investigated if the children's interaction
      with a human differed from the interaction with a social robot during a play
      task. Also, it was examined if the two conditions differed in their ability to
      elicit interaction with a human accompanying the child during the task.
      Interaction of the children with both partners did not differ apart from the eye
      contact. Participants had more eye-contact with the social robot compared to the
      eye-contact with the human. The conditions did not differ regarding the
      interaction elicited with the human accompanying the child. 

PMID- 26304032
TI  - Inflammation-induced expression of the alarmin interleukin 33 can be suppressed
      by galacto-oligosaccharides.
AB  - BACKGROUND: The alarmin interleukin 33 (IL-33) and its receptor ST2 play an
      important role in mucosal barrier tissues, and seem to be crucial for Th2-cell
      mediated host defense. Galacto-oligosaccharides (GOS), used in infant formulas,
      exhibit gut and immune modulatory effects. To enhance our understanding of the
      immunomodulatory capacity of GOS, this study investigated the impact of dietary
      GOS intervention on IL-33 and ST2 expression related to intestinal barrier
      dysfunction and asthma. METHODS: B6C3F1 and BALB/c mice were fed a control diet
      with or without 1% GOS. To simulate intestinal barrier dysfunction, B6C3F1 mice
      received a gavage with the mycotoxin deoxynivalenol (DON). To mimic asthma-like
      inflammatory airway responses, BALB/c mice were sensitized on day 0 and
      challenged on days 7-11 with house-dust mite (HDM) allergen. Samples from the
      intestines and lungs were collected for IL-33 and ST2 analysis by qRT-PCR,
      immunoblotting and immunohistochemistry. RESULTS: Dietary GOS counteracted the
      DON-induced IL-33 mRNA expression and changed the IL-33 distribution pattern in
      the mouse small intestine. The IL-33 mRNA expression was positively correlated to
      the intestinal permeability. A strong positive correlation was also observed
      between IL-33 mRNA expression in the lung and the number of bronchoalveolar fluid
      cells. Reduced levels of IL-33 protein, altered IL-33 distribution and reduced
      ST2 mRNA expression were observed in the lungs of HDM-allergic mice after GOS
      intervention. CONCLUSIONS: Dietary GOS mitigated IL-33 at the mucosal surfaces in
      a murine model for intestinal barrier dysfunction and HDM-induced asthma. This
      promising effect may open up new avenues to use GOS not only as a prebiotic in
      infant nutrition, but also as a functional ingredient that targets inflammatory
      processes and allergies associated with IL-33 expression.

PMID- 26304034
TI  - Point of care ultrasound in the NICU-training, accreditation and ownership.

PMID- 26304033
TI  - Methylomic analysis of salivary DNA in childhood ADHD identifies altered DNA
      methylation in VIPR2.
AB  - BACKGROUND: Peripheral epigenetic marks hold promise for understanding
      psychiatric illness and may represent fingerprints of gene-environment
      interactions. We conducted an initial examination of CpG methylation variation in
      children with or without attention-deficit/hyperactivity disorder (ADHD).
      METHODS: Children age 7-12 were recruited, screened, evaluated and assigned to
      ADHD or non-ADHD groups by defined research criteria. Two independent age-matched
      samples were examined, a discovery set (n = 92, all boys, half control, half
      ADHD) and a confirmation set (n = 20, half ADHD, all boys). 5-methylcytosine
      levels were quantified in salivary DNA using the Illumina 450 K HumanMethylation
      array. Genes for which multiple probes were nominally significant and had a beta
      difference of at least 2% were evaluated for biological relevance and prioritized
      for confirmation and sequence validation. Gene pathways were explored and
      described. RESULTS: Two genes met the criteria for confirmation testing, VIPR2
      and MYT1L; both had multiple probes meeting cutoffs and strong biological
      relevance. Probes on VIPR2 passed FDR correction in the confirmation set and were
      confirmed through bisulfite sequencing. Enrichment analysis suggested involvement
      of gene sets or pathways related to inflammatory processes and modulation of
      monoamine and cholinergic neurotransmission. CONCLUSIONS: Although it is unknown
      to what extent CpG methylation seen in peripheral tissue reflect transcriptomic
      changes in the brain, these initial results indicate that peripheral DNA
      methylation markers in ADHD may be promising and suggest targeted hypotheses for
      future study in larger samples.

PMID- 26304035
TI  - The beta-N-acetylhexosaminidase gene family in the brown planthopper, Nilaparvata
      lugens.
AB  - beta-N-Acetylhexosaminidases (HEXs) are enzymes that can degrade the chitin
      oligosaccharides that are produced by the activity of chitinases on chitin in
      insects. Using bioinformatic methods based on genome and transcriptome databases,
      11 beta-N-acetylhexosaminidase genes (NlHexs) in Nilaparvata lugens were
      identified and characterized. Phylogenetic analysis revealed a six-grouped tree
      topology. The O-Linked N-acetylglucosaminidase (O-GlcNAcase) group includes
      NlHex11, which harbours a catalytic domain that differs from that of the other 10
      NlHexs. Observations of the expression of NlHexs during different developmental
      stages revealed that NlHex4 is expressed with periodicity during moulting.
      Although the tissue-specific expression patterns of most NlHexs were nonspecific,
      NlHex4 was found to be expressed mainly in the female reproductive system as well
      as in the integument. RNA interference (RNAi) demonstrated failure to shed the
      old cuticle only in the nymphs treated with double-stranded RNA (dsRNA) targeting
      NlHex4, and these nymphs eventually died; no observable morphological
      abnormalities were found in insects treated with dsRNAs targeting the other 10
      NlHexs. Based on this study and our previous analyses, a '5 + 1 + 3' pattern of
      chitinolytic enzymes is proposed, in which five chitinases, one NlHEX and three
      chitin deacetylases are required for moulting in N. lugens. A better
      understanding of chitin metabolism in the hemimetabolous insect, N. lugens, would
      be achieved by considering three chitinolytic enzyme families: chitinase, chitin
      deacetylase and beta-N-acetylhexosaminidase. 

PMID- 26304036
TI  - Perivascular Mesenchymal Stem Cells From the Adult Human Brain Harbor No
      Instrinsic Neuroectodermal but High Mesodermal Differentiation Potential.
AB  - Brain perivascular cells have recently been identified as a novel mesodermal cell
      type in the human brain. These cells reside in the perivascular niche and were
      shown to have mesodermal and, to a lesser extent, tissue-specific differentiation
      potential. Mesenchymal stem cells (MSCs) are widely proposed for use in cell
      therapy in many neurological disorders; therefore, it is of importance to better
      understand the "intrinsic" MSC population of the human brain. We systematically
      characterized adult human brain-derived pericytes during in vitro expansion and
      differentiation and compared these cells with fetal and adult human brain-derived
      neural stem cells (NSCs) and adult human bone marrow-derived MSCs. We found that
      adult human brain pericytes, which can be isolated from the hippocampus and from
      subcortical white matter, are-in contrast to adult human NSCs-easily expandable
      in monolayer cultures and show many similarities to human bone marrow-derived
      MSCs both regarding both surface marker expression and after whole transcriptome
      profile. Human brain pericytes showed a negligible propensity for neuroectodermal
      differentiation under various differentiation conditions but efficiently
      generated mesodermal progeny. Consequently, human brain pericytes resemble bone
      marrow-derived MSCs and might be very interesting for possible autologous and
      endogenous stem cell-based treatment strategies and cell therapeutic approaches
      for treating neurological diseases. SIGNIFICANCE: Perivascular mesenchymal stem
      cells (MSCs) recently gained significant interest because of their appearance in
      many tissues including the human brain. MSCs were often reported as being
      beneficial after transplantation in the central nervous system in different
      neurological diseases; therefore, adult brain perivascular cells derived from
      human neural tissue were systematically characterized concerning neural stem cell
      and MSC marker expression, transcriptomics, and mesodermal and inherent
      neuroectodermal differentiation potential in vitro and in vivo after in utero
      transplantation. This study showed the lack of an innate neuronal but high
      mesodermal differentiation potential. Because of their relationship to
      mesenchymal stem cells, these adult brain perivascular mesodermal cells are of
      great interest for possible autologous therapeutic use.

PMID- 26304038
TI  - Variability of the caprine whey protein genes and their association with milk
      yield, composition and renneting properties in the Sarda breed. 1. The LALBA
      gene.
AB  - The 5' flanking region and 3' UTR of the caprine LALBA gene were analysed by SSCP
      and sequencing. A total of nine SNPs were detected: three in the promoter region,
      two were synonymous coding SNPs at exon-1, and four SNPs were in exon-4, within
      the 3'UTR. The nucleotide changes located in the promoter region (c.-358T>C, c.
      163G>A, c.-121T>G) were genotyped by SSCP in 263 Sarda goats to evaluate their
      possible effect on milk yield, composition and renneting properties. We observed
      an effect of the three SNPs on milk yield and lactose content. Genotypes TT and
      CT at c.-358T>C (P A (P C and c.-121T>G were part of transcription factors
      binding sites, potentially involved in modulating the LALBA gene expression. The
      LALBA genotype affected renneting properties (P < 0.001), as heterozygotes c.
      358CT and c.-163GA were characterised by delayed rennet coagulation time and curd
      firming time and the lowest value of curd firmness. The present investigation
      increases the panel of SNPs and adds new information about the effects of the
      caprine LALBA gene polymorphism.

PMID- 26304037
TI  - Insulin-Producing Endocrine Cells Differentiated In Vitro From Human Embryonic
      Stem Cells Function in Macroencapsulation Devices In Vivo.
AB  - The PEC-01 cell population, differentiated from human embryonic stem cells
      (hESCs), contains pancreatic progenitors (PPs) that, when loaded into
      macroencapsulation devices (to produce the VC-01 candidate product) and
      transplanted into mice, can mature into glucose-responsive insulin-secreting
      cells and other pancreatic endocrine cells involved in glucose metabolism. We
      modified the protocol for making PEC-01 cells such that 73%-80% of the cell
      population consisted of PDX1-positive (PDX1+) and NKX6.1+ PPs. The PPs were
      further differentiated to islet-like cells (ICs) that reproducibly contained 73%
      89% endocrine cells, of which approximately 40%-50% expressed insulin. A large
      fraction of these insulin-positive cells were single hormone-positive and
      expressed the transcription factors PDX1 and NKX6.1. To preclude a significant
      contribution of progenitors to the in vivo function of ICs, we used a simple
      enrichment process to remove remaining PPs, yielding aggregates that contained
      93%-98% endocrine cells and 1%-3% progenitors. Enriched ICs, when encapsulated
      and implanted into mice, functioned similarly to the VC-01 candidate product,
      demonstrating conclusively that in vitro-produced hESC-derived insulin-producing
      cells can mature and function in vivo in devices. A scaled version of our
      suspension culture was used, and the endocrine aggregates could be cryopreserved
      and retain functionality. Although ICs expressed multiple important beta cell
      genes, the cells contained relatively low levels of several maturity-associated
      markers. Correlating with this, the time to function of ICs was similar to PEC-01
      cells, indicating that ICs required cell-autonomous maturation after delivery in
      vivo, which would occur concurrently with graft integration into the host.
      SIGNIFICANCE: Type 1 diabetes (T1D) affects approximately 1.25 million people in
      the U.S. alone and is deadly if not managed with insulin injections. This paper
      describes the production of insulin-producing cells in vitro and a new protocol
      for producing the cells, representing another potential cell source for a
      diabetes cell therapy. These cells can be loaded into a protective device that is
      implanted under the skin. The device is designed to protect the cells from immune
      rejection by the implant recipient. The implant can engraft and respond to
      glucose by secreting insulin, thus potentially replacing the beta cells lost in
      patients with T1D.

PMID- 26304039
TI  - Aneurysm of the Aortic Isthmus.

PMID- 26304040
TI  - Fever is not a contraindication for a blanket.

PMID- 26304041
TI  - The effect of LH supplementation to the GnRH antagonist protocol in advanced
      reproductive ageing women: a prospective randomized controlled study.
AB  - OBJECTIVE: Although the fundamental significance of both LH and FSH for adequate
      ovarian folliculogenesis and steroidogenesis has been extensively discussed, the
      clinical implication of recombinant (r) LH to rFSH for ovarian stimulation
      employing the GnRH antagonist protocol remains to be elucidated. The aim of this
      prospective randomized controlled study was to explore whether rLH
      supplementation to rFSH following GnRH antagonist has an added value to the late
      follicular ovarian steroidogenesis in the advanced reproductive aged women.
      DESIGN AND SUBJECTS: Sixty-three consecutive infertile women above 35 years of
      age and/or with a previous low ovarian response admitted for IVF/ICSI treatment
      were prospectively randomized. Women in the study and control groups were
      similarly treated employing the rFSH 300 IU/day and the flexible GnRH antagonist
      0.25 mg/day protocol. On the day of antagonist initiation, rLH 150 IU/day was
      added only to the study group and continued till the hCG day. RESULTS: Serum E2
      level on hCG day did not significantly differ between the study and control
      groups, corresponding to 1268 +/- 1006 and 1113 +/- 669 pg/mL, respectively (P =
      0.9). In the study group, the duration of GnRH antagonist administration was
      significantly lower than the control group corresponding to 5.0 +/- 1.5 to 4.0 +/
      1.5 days, respectively (P < 0.05). The total dosage of rFSH administration did
      not differ between the two groups. CONCLUSIONS: rLH supplementation to rFSH
      following GnRH antagonist administration employing the flexible protocol does not
      seem to significantly augment serum E2 level on the day of hCG administration in
      the advanced reproductive ageing women. This suggests that endogenous serum LH
      levels following GnRH antagonist initiation are sufficient for adequate late
      follicular ovarian steroidogenesis in this setting.

PMID- 26304042
TI  - Planar dGEMRIC Maps May Aid Imaging Assessment of Cartilage Damage in
      Femoroacetabular Impingement.
AB  - BACKGROUND: Three-dimensional (3-D) delayed gadolinium-enhanced MRI of cartilage
      (dGEMRIC) helps quantify biochemical changes in articular cartilage that
      correlate with early-stage osteoarthritis. However, dGEMRIC analysis is performed
      slice by slice, limiting the potential of 3-D data to give an overall impression
      of cartilage biochemistry. We previously developed a computational algorithm to
      produce unfolded, or "planar," dGEMRIC maps of acetabular cartilage, but have
      neither assessed their application nor determined whether MRI-based grading of
      cartilage damage or dGEMRIC measurements predict intraoperative findings in hips
      with symptomatic femoroacetabular impingement (FAI). QUESTIONS/PURPOSES: (1) Does
      imaging-based assessment of acetabular cartilage damage correlate with
      intraoperative findings in hips with symptomatic FAI? (2) Does the planar dGEMRIC
      map improve this correlation? (3) Does the planar map improve the correlation
      between the dGEMRIC index and MRI-based grading of cartilage damage in hips with
      symptomatic FAI? (4) Does the planar map improve imaging-based evaluation time
      for hips with symptomatic FAI? METHODS: We retrospectively studied 47 hips of 45
      patients with symptomatic FAI who underwent hip surgery between 2009 and 2013 and
      had a 1.5-T 3-D dGEMRIC scan within 6 months preoperatively. Our cohort included
      25 males and 20 females with a mean +/- SD age at surgery of 29 +/- 11 years.
      Planar dGEMRIC maps were generated from isotropic, sagittal oblique TrueFISP and
      T1 sequences. A pediatric musculoskeletal radiologist with experience in hip MRI
      evaluated studies using radially reformatted sequences. For six acetabular
      subregions (anterior-peripheral [AP]; anterior-central [AC]; superior-peripheral
      [SP]; superior-central [SC]; posterior-peripheral [PP]; posterior-central [PC]),
      modified Outerbridge cartilage damage grades were recorded and region-of-interest
      T1 averages (the dGEMRIC index) were measured. Beck's intraoperative cartilage
      damage grades were compared with the Outerbridge grades and dGEMRIC indices. For
      a subset of 26 hips, 13 were reevaluated with the map and 13 without the map, and
      total evaluation times were recorded. RESULTS: There were no meaningful
      differences in the correlations obtained with versus without referencing the
      planar maps. Planar map-independent Outerbridge grades had a notable (p < 0.05)
      Spearman's rank correlation (rho) with Beck's grades that was moderate in AP, SC,
      and PC (0.3 < rho < 0.5) and strong in SP (rho > 0.5). For map-dependent
      Outerbridge grades, rho was moderate in AP, AC, and SC and strong in SP. Map
      independent dGEMRIC indices had a rho with Beck's grades that was moderate in AP
      and SC (-0.3 > rho > -0.5) and strong in SP (rho < -0.5). For map-dependent
      dGEMRIC indices, rho was moderate in SC and strong in SP. Similarly, there were
      no meaningful, map-dependent differences in the correlations. When comparing
      Outerbridge grades and dGEMRIC indices, there were notable correlations across
      all subregions. Without the planar map, rho was moderate in AC and PC and strong
      in AP, SP, SC, and PP. With the map, rho was strong in all six subregions. In AC,
      there was a notable map-dependent improvement in this correlation (p < 0.001).
      Finally, referencing the planar dGEMRIC map during evaluation was associated with
      a decrease in mean evaluation time, from 207 +/- 32 seconds to 152 +/- 33 seconds
      (p = 0.001). CONCLUSIONS: Our work challenges the weak correlation between
      dGEMRIC and intraoperative findings of cartilage damage that was previously
      reported in hips with symptomatic FAI, suggesting that dGEMRIC has potential
      diagnostic use for this patient population. The planar dGEMRIC maps did not
      meaningfully alter the correlation of imaging-based evaluation of cartilage
      damage with intraoperative findings; however, they notably improved the
      correlation of dGEMRIC and MRI-based grading in AC, and their use incurred no
      additional time cost to imaging-based evaluation. Therefore, the planar maps may
      improve dGEMRIC's use as a continuous proxy for an otherwise discrete and
      simplified MRI-based grade of cartilage damage in hips with symptomatic FAI.
      LEVEL OF EVIDENCE: Level III, diagnostic study.

PMID- 26304044
TI  - CORR Insights((r)): Is There a Benefit to Modularity in 'Simpler' Femoral
      Revisions?

PMID- 26304043
TI  - What Factors are Associated With a Surgical Site Infection After Operative
      Treatment of an Elbow Fracture?
AB  - BACKGROUND: Surgical site infections are one of the more common major
      complications of elbow fracture surgery and can contribute to other adverse
      outcomes, prolonged hospital stays, and increased healthcare costs.
      QUESTIONS/PURPOSES: We asked: (1) What are the factors associated with a surgical
      site infection after elbow fracture surgery? (2) When taking the subset of closed
      elbow fractures only, what are the factors associated with a surgical site
      infection? (3) What are the common organisms isolated from an elbow infection
      after open treatment? METHODS: One thousand three hundred twenty adult patients
      underwent surgery for an elbow fracture between January 2002 and July 2014 and
      were included in our study. Forty-eight of 1320 patients (4%) had a surgical site
      infection develop. Thirty-four of 1113 patients with a closed fracture (3%) had a
      surgical site infection develop. RESULTS: For all elbow fractures, use of plate
      and screw fixation (adjusted odds ratio [OR]= 2.2; 95% CI, 1.0-4.5; p = 0.041)
      and use of external fixation before surgery (adjusted OR = 4.7; 95% CI, 1.1-21; p
      = 0.035) were associated with higher infection rates. When subset analysis was
      performed for closed fractures, only smoking (adjusted OR = 2.2; 95% CI, 1.1-4.5;
      p = 0.023) was associated with higher infection rates. Staphylococcus aureus was
      the most common bacteria cultured (59%). CONCLUSIONS: The only modifiable risk
      factor for a surgical site infection after open reduction and internal fixation
      was cigarette smoking. Plate fixation and temporary external fixation are likely
      surrogates for more complex injuries, therefore no recommendations should be
      inferred from this association. Surgeons should counsel patients who smoke. LEVEL
      OF EVIDENCE: Level IV, prognostic study.

PMID- 26304045
TI  - Does Surgical Stabilization of Lateral Compression-type Pelvic Ring Fractures
      Decrease Patients' Pain, Reduce Narcotic Use, and Improve Mobilization?
AB  - BACKGROUND: Debate remains over the role of surgical treatment in minimally
      displaced lateral compression (Young-Burgess, LC, OTA 61-B1/B2) pelvic ring
      injuries. Lateral compression type 1 (LC1) injuries are defined by an impaction
      fracture at the sacrum; type 2 (LC2) are defined by a fracture that extends
      through the posterior iliac wing at the level of the sacroiliac joint. Some
      believe that operative stabilization of these fractures limits pain and eases
      mobilization, but to our knowledge there are few controlled studies on the topic.
      QUESTIONS/PURPOSES: (1) Does operative stabilization of LC1 and LC2 pelvic
      fractures decrease patients' narcotic use and lower their visual analog scale
      pain scores? (2) Does stabilization allow patients to mobilize earlier with
      physical therapy? METHODS: This retrospective study of LC1 and LC2 fractures
      evaluated patients treated definitively at one institution from 2007 to 2013. All
      patients treated surgically, all nonoperative LC2, and all nonoperative LC1
      fractures with complete sacral injury were included. In general, LC1 or LC2
      fractures with greater than 10 mm of displacement and/or sagittal/axial plane
      deformity on static radiographs were treated surgically. One hundred fifty-eight
      patients in the LC1 group (107 [of 697 screened] nonoperative, 51 surgical) and
      123 patients in the LC2 group (78 nonoperative, 45 surgical) met inclusion
      criteria. The surgical and nonoperative groups were matched for fracture type. To
      account for differences between patients treated surgically and nonoperatively,
      we used propensity modeling techniques incorporating treatment predictors.
      Propensity scores demonstrated good overlap and were used as part of multiple
      variable regression models to account for selection bias between the surgically
      treated and nonoperative groups. Patient-reported pain scores and narcotic
      administration were tallied in 24-hour increments during the first 24 hours of
      hospitalization, at 48 hours after intervention, and in the 24 hours before
      discharge. Time from intervention to mobilization out of bed was recorded;
      intervention was defined as the date of definitive surgical intervention or the
      day the surgeon determined the patient would be treated without surgery. RESULTS:
      There was no difference in the narcotics distributed to any of the groups with
      the exception that the patients with surgically treated LC2 fractures used, on
      average (mean [95% confidence interval]) 40.2 (-72.9 to -7.6) mg morphine less at
      the 48-hour mark (p = 0.016). In general, there were no differences between the
      groups' pain scores. The surgically treated patients with LC1 fractures mobilized
      1.7 (-3.3 to -0.01) days earlier (p = 0.034) than their nonoperative
      counterparts. There was no difference in the LC2 cohort in terms of time to
      mobilization between those treated with and without surgery. CONCLUSIONS: There
      were few differences in pain scores and morphine use between the surgical and
      nonoperative groups, and the differences observed likely were not clinically
      important. We found no evidence that surgical stabilization of certain LC1 and
      LC2 pelvic fractures improves patients' pain, decreases their narcotic use, and
      improves time to mobilization. A randomized trial of patients with similar
      fractures and similar degrees initial displacement would help remove some of the
      confounders present in this study. LEVEL OF EVIDENCE: Level III, therapeutic
      study.

PMID- 26304046
TI  - The utility of a 'non-significant' coronary angiogram.
AB  - BACKGROUND: Coronary angiography is the gold standard for assessing coronary
      artery disease (CAD). In many patients with chest pain, no or mild CAD (< 50%
      stenosis) is found. It is uncertain whether this 'non-significant' result
      influences management and outcomes. We reviewed characteristics and outcomes in a
      contemporary cohort of chest pain referrals who had mild or absent CAD on
      coronary angiography. METHOD: All patients undergoing coronary angiography at
      Auckland City Hospital during July 2010-October 2011 were reviewed (n = 2983). Of
      these, 12.3% (n = 366) underwent coronary angiography for evaluation of chest
      pain and were found to have absent or mild CAD. These patients were followed up
      for 2.3 +/- 0.6 years. RESULTS: Mean age was 60.0 +/- 12.3 years, 56.1% were
      female. The ECG was abnormal in 55.0% of patients. Stress testing for inducible
      ischaemia was undertaken in 40.7% of patients and was abnormal in 57.7%.
      Following angiography, 43.2% had no changes to cardiac medications. Additional
      drug therapy (aspirin, statin, beta-blockers, ACE-inhibitor) was commenced in
      around 14.2-22.1% of cases. These drugs were discontinued in 4.1-8.2% of
      patients. Rates of major adverse cardiovascular events and readmissions with
      chest pain were 0.3% (1) and 1.9% (7) respectively at 30 days, and 1.9% (7) and
      6.0% (22) at 1 year. CONCLUSION: Although even non-obstructive atheroma may
      justify medical therapy to limit disease progression, our findings may suggest
      that in these cases, invasive coronary angiography, may not lead to the
      patient/physician reassurance justified by historical data.

PMID- 26304048
TI  - A systematic review and meta-analysis of metformin among patients with polycystic
      ovary syndrome undergoing assisted reproductive technology procedures.
AB  - BACKGROUND: Metformin is used among patients with polycystic ovary syndrome
      (PCOS), but findings for its effects on outcomes of assisted reproductive
      technology (ART) have been conflicting. OBJECTIVES: To compare ART outcomes among
      women with PCOS who were and were not given metformin. SEARCH STRATEGY: Databases
      were searched for reports published in English between 2002 and 2013, using
      combinations of the terms "polycystic ovary syndrome," "PCOS," "insulin
      sensitizing," and "metformin." SELECTION CRITERIA: Randomized controlled trials
      of metformin versus placebo among women with PCOS undergoing ART were included if
      they assessed rates of pregnancy, live birth, spontaneous abortion, multiple
      pregnancy, and/or ovarian hyperstimulation syndrome (OHSS). DATA COLLECTION AND
      ANALYSIS: Data were extracted from included studies. The Mantel-Haenzel random
      effects model was used for meta-analyses. MAIN RESULTS: Twelve studies (1516
      participants) were included. No significant differences were recorded between
      metformin and placebo groups for rates of pregnancy (risk ratio [RR] 1.11, 95% CI
      0.92-1.33), live birth (RR 1.12, 0.92-1.36), spontaneous abortion (RR 1.00, 0.60
      1.67), or multiple pregnancy (RR 0.96, 0.47-1.96). However, OHSS rate was
      significantly lower among patients who received metformin than among those who
      received placebo (RR 0.44, 0.26-0.77). CONCLUSIONS: Metformin does not improve
      ART outcomes among patients with PCOS, but does significantly reduce their risk
      of OHSS.

PMID- 26304050
TI  - Load dissipation by corn residue on tilled soil in laboratory and field-wheeling
      conditions.
AB  - Crop residues may partially dissipate applied loads and reduce soil compaction.
      We evaluated the effect of corn residue on energy-applied dissipation during
      wheeling. The experiment consisted of a preliminary laboratory test and a
      confirmatory field test on a Paleaudalf soil. In the laboratory, an adapted
      Proctor test was performed with three energy levels, with and without corn
      residue. Field treatments consisted of three 5.1 Mg tractor wheeling intensities
      (0, 2, and 6), with and without 12 Mg ha(-1) corn residue on the soil surface.
      Corn residue on the soil surface reduced soil bulk density in the adapted Proctor
      test. By applying energy of 52.6 kN m m(-3) , soil dissipated 2.98% of applied
      energy, whereas with 175.4 kN m m(-3) a dissipation of 8.60% was obtained. This
      result confirms the hypothesis that surface mulch absorbs part of the compaction
      effort. Residue effects on soil compaction observed in the adapted Proctor test
      was not replicated under subsoiled soil field conditions, because of differences
      in applied pressure and soil conditions (structure, moisture and volume
      confinement). Nevertheless, this negative result does not mean that straw has no
      effect in the field. Such effects should be measured via stress transmission and
      compared to soil load-bearing capacity, rather than on bulk deformations.
      Wheeling by heavy tractor on subsoiled soil increased compaction, independently
      of surface residue. Two wheelings produced a significantly increase, but six
      wheelings did not further increase compaction. Reduced traffic intensity on
      recently tilled soil is necessary to minimize soil compaction, since traffic
      intensity show a greater effect than surface mulch on soil protection from
      excessive compaction. (c) 2015 Society of Chemical Industry. 

PMID- 26304049
TI  - Correlates and Experiences of HIV Stigma in Prisoners Living With HIV in
      Indonesia: A Mixed-Method Analysis.
AB  - In Indonesia, the syndemic nature of HIV, drug use, and incarceration may
      influence experiences of stigma for HIV-infected prisoners. This mixed-method
      study explores HIV stigma in prisoners living with HIV in Indonesia. Randomly
      selected male HIV-infected prisoners (n = 102) from two large prisons in Jakarta
      completed in-depth interviews and a structured HIV stigma survey. Quantitative
      results found four groups of HIV-infected prisoners with significantly higher HIV
      stigma levels, including those: (a) with drug-related offenses, (b) seeking help
      to decrease drug use, (c) diagnosed with HIV before the current incarceration,
      and (d) who had not disclosed their HIV status to family members or friends.
      Qualitative results highlighted the prominent role of HIV stigma in decisions to
      disclose HIV status to family members, partners, and other prisoners.
      Interventions should address HIV stigma in HIV-infected prisoners in Indonesia to
      achieve HIV treatment as prevention goals.

PMID- 26304051
TI  - Using appreciative inquiry to transform student nurses' image of nursing.
AB  - INTRODUCTION: Literature provides adequate evidence of a poor perception of
      nursing within the profession, resulting in high rates of attrition of student
      nurses and newly qualified nurses. The nursing profession, in particular nurse
      educators, has an ethical and professional responsibility to find innovative
      strategies to promote the positive image of nursing amongst student nurses.
      PURPOSE: The purpose of the study was to explore the potential of appreciative
      inquiry (AI) as an intervention teaching strategy to transform student nurses'
      image of nursing. DESIGN: A quantitative, quasi-experimental, explorative
      descriptive design comprising the pretest, appreciative inquiry as intervention,
      and the post-test was used. METHODS: Convenience sampling was used to select
      third and fourth year college and university student nurses in the Gauteng
      province of South Africa for the pre- and the post-test respectively. Data were
      collected by means of a questionnaire and analysed by SPSS version 20.0.
      FINDINGS: The pretest results revealed a mix of positive and negative perceptions
      of the image of nursing amongst student nurses. The negative perceptions of the
      image of nursing that needed intervention included the working conditions of
      nurses, and the perception of nursing as a profession that was not respected and
      appreciated. The post-test results showed a significant and positive change in
      the student nurses' perception of the image of nursing as a respected and
      appreciated profession. Although AI resulted in a negative to positive change in
      some aspects of student nurses' image of nursing, the negative perceptions of the
      working conditions of nurses remained and became more negative. The positive
      image of gender in nursing was enhanced following the implementation of AI.
      CONCLUSION: Appreciative inquiry demonstrated potential as a teaching strategy to
      produce a positive nursing image change and positive orientation towards nursing
      amongst student nurses.

PMID- 26304052
TI  - Life stories of young women who experience rejection from their mothers.
AB  - BACKGROUND: When a daughter perceives rejection from her mother, she is bound to
      be sensitive to rejection for most if not all of her life. Such an experience
      influences almost all future relationships. OBJECTIVES: The purpose of this
      research was to explore and describe the life stories of young women who
      perceived rejection from their mothers and to formulate guidelines to assist
      them. METHOD: A phenomenological interpretive method that is explorative,
      descriptive, and contextual was used to explore everyday life experiences.
      Network sampling was used. In-depth phenomenological interviews were conducted
      with the young women so that they could define the most important dimensions of
      their life stories and elaborate on what is relevant to them. They were asked:
      'Tell me your life story.' One of the authors also had a life story of perceived
      maternal rejection; hence an auto-ethnography was critical and was included in
      the study. Thematic data analysis was applied. RESULTS: Themes that emerged from
      the data were that the young women: (1) perceive ongoing challenges in forming
      and sustaining relationships in their lives; (2) experience their lives as
      conflicted because their relationship with the central core of their existence,
      their mother, is perceived as tumultuous; and (3) experience fundamental links to
      be missing in their 'mother-daughter relationship'. CONCLUSION: Only a few women
      were interviewed regarding perceived rejection from their mothers. Further
      research in this regard is imperative.

PMID- 26304053
TI  - Undergraduate nurses reflections on Whatsapp use in improving primary health care
      education.
AB  - BACKGROUND: The global use of mobile devices with their connectivity capacity,
      and integrated with the affordances of social media networks, provides a resource
      rich platform for innovative student-directed learning experiences. OBJECTIVE:
      The objective of this study was to review the experiences of undergraduate nurses
      on the improvement of primary health care education at a School of Nursing at a
      University in the Western Cape, South Africa, through the incorporation of a
      social media application, WhatsApp. METHOD: A qualitative, exploratory,
      descriptive, and contextual design was used to explore and describe data
      collected from a purposive sample of 21 undergraduate nursing students. The study
      population was engaged in a WhatsApp discussion group to enhance their
      integration of theory and clinical practice of the health assessment competency
      of the Primary Health Care Module. Participants submitted electronic reflections
      on their experiences in the WhatsApp discussion group via email on completion of
      the study. Thematic analysis of the qualitative data collected was done according
      to Tesch's (1990) steps of descriptive data analysis in order to identify the
      major themes in the study. The electronic reflections were analysed to explore
      their rich, reflective data. RESULTS: Seven themes were identified that included:
      positive experiences using the WhatsApp group; the usefulness of WhatsApp for
      integrating theory and clinical practice; the availability of resources for test
      preparation; opportunity for clarification; anonymity; exclusion of students as a
      result of the lack of an appropriate device, and the application caused the
      battery of the device to run flat quickly. CONCLUSION: The results of the
      experiences of students in the WhatsApp discussion group could be used to inform
      the use of social media applications in teaching and learning, with the purpose
      of enhancing the integration of the theory and clinical practice.

PMID- 26304054
TI  - Scleredema. A multicentre study of characteristics, comorbidities, course and
      therapy in 44 patients.
AB  - BACKGROUND: The prognostic and therapeutic features of scleredema are poorly
      documented. OBJECTIVES: To describe the characteristics of patients with
      scleredema regarding demographics, clinical characteristics, comorbidities,
      therapeutic interventions and course. METHODS: We conducted a retrospective
      multicentre study. RESULTS: We identified 44 patients (26 men).The mean age at
      diagnosis was 53.8 years. The most common associated disorders were
      endocrine/metabolic diseases including 30 patients suffering from diabetes,
      mostly type 2 diabetes. Monoclonal gammopathies were confirmed in five cases. A
      preceding respiratory tract infection was not a feature. Treatments with
      different combination or sequential modalities were used with variable results.
      Phototherapy (UVA1 or PUVA) was the treatment associated with higher, although
      partial response. Systemic corticosteroids and immunosuppressive drugs were
      reserved to patients with severe disease in whom phototherapy had failed or for
      patients with multiple myeloma. Forty-one patients were followed up (mean period:
      32.2 months).Thirty-nine patients are alive, 30 with and 9 without skin disease.
      Two patients died of cardiovascular complications due to myeloma and severe
      diabetes. CONCLUSIONS: Scleredema is a chronic debilitating disease associated
      with diabetes and metabolic syndrome, unresponsive to various treatments but not
      necessarily a life-threatening condition. Although there is no definitive
      treatment, phototherapy should be attempted first. Treatment of primary disease
      including strict glycaemic control combined with physical therapy should be also
      employed.

PMID- 26304056
TI  - White Matter Integrity Dissociates Verbal Memory and Auditory Attention Span in
      Emerging Adults with Congenital Heart Disease.
AB  - White matter disruptions have been identified in individuals with congenital
      heart disease (CHD). However, no specific theory-driven relationships between
      microstructural white matter disruptions and cognition have been established in
      CHD. We conducted a two-part study. First, we identified significant differences
      in fractional anisotropy (FA) of emerging adults with CHD using Tract-Based
      Spatial Statistics (TBSS). TBSS analyses between 22 participants with CHD and 18
      demographically similar controls identified five regions of normal appearing
      white matter with significantly lower FA in CHD, and two higher. Next, two
      regions of lower FA in CHD were selected to examine theory-driven differential
      relationships with cognition: voxels along the left uncinate fasciculus (UF; a
      tract theorized to contribute to verbal memory) and voxels along the right middle
      cerebellar peduncle (MCP; a tract previously linked to attention). In CHD, a
      significant positive correlation between UF FA and memory was found, r(20)=.42,
      p=.049 (uncorrected). There was no correlation between UF and auditory attention
      span. A positive correlation between MCP FA and auditory attention span was
      found, r(20)=.47, p=.027 (uncorrected). There was no correlation between MCP and
      memory. In controls, no significant relationships were identified. These results
      are consistent with previous literature demonstrating lower FA in younger CHD
      samples, and provide novel evidence for disrupted white matter integrity in
      emerging adults with CHD. Furthermore, a correlational double dissociation
      established distinct white matter circuitry (UF and MCP) and differential
      cognitive correlates (memory and attention span, respectively) in young adults
      with CHD.

PMID- 26304057
TI  - Social Perspective Taking and Empathy in Children with Fetal Alcohol Spectrum
      Disorders.
AB  - Children with fetal alcohol spectrum disorders (FASD) show sociobehavioral
      impairments; however, the social cognitive profile contributing to these
      impairments is poorly understood. This study compared social perspective taking
      and empathy in children with FASD versus typically developing controls (TDC).
      Thirty-seven children with FASD and 21 TDC participated. Measures included parent
      rated CBCL and SSIS, and NEPSY-II Theory of Mind, Test of Social Cognition and
      Index of Empathy. Parents rated the FASD group higher than TDC on indices of
      behavior problems and lower on indices of social skills and empathy. Children
      with FASD scored significantly below TDC on tasks requiring complex social
      cognition. The majority of correlations between social cognition and parent
      ratings were not significant in FASD and TDC, with the exception of a negative
      correlation between self-reported empathy and parent-rated behavior difficulties
      in TDC. FASD subgroup analyses revealed lower theory of mind and empathy scores
      among children with ARND than pFAS/FAS. With regard to sex, males with FASD were
      rated as having more behavior difficulties than females, whereas TDC females
      obtained higher empathy ratings than males. In both groups, females scored higher
      on theory of mind and empathy indices. On theory of mind tasks, older children
      with FASD performed below younger, whereas younger TDC children performed more
      poorly than older. Children with FASD show reduced functioning on indices of
      sociobehavioral and social cognition, and the effects are influenced by sex and
      age. These findings provide insight into the clinical and social profile of
      children with FASD.

PMID- 26304055
TI  - Intra-individual Variability in Prodromal Huntington Disease and Its Relationship
      to Genetic Burden.
AB  - The current study sought to examine the utility of intra-individual variability
      (IIV) in distinguishing participants with prodromal Huntington disease (HD) from
      nongene-expanded controls. IIV across 15 neuropsychological tasks and within-task
      IIV using a self-paced timing task were compared as a single measure of
      processing speed (Symbol Digit Modalities Test [SDMT]) in 693 gene-expanded and
      191 nongene-expanded participants from the PREDICT-HD study. After adjusting for
      depressive symptoms and motor functioning, individuals estimated to be closest to
      HD diagnosis displayed higher levels of across- and within-task variability when
      compared to controls and those prodromal HD participants far from disease onset
      (F ICV(3,877)=11.25; p<.0001; F PacedTiming(3,877)=22.89; p<.0001). When
      prodromal HD participants closest to HD diagnosis were compared to controls,
      Cohen's d effect sizes were larger in magnitude for the within-task variability
      measure, paced timing (-1.01), and the SDMT (-0.79) and paced tapping coefficient
      of variation (CV) (-0.79) compared to the measures of across-task variability [CV
      (0.55); intra-individual standard deviation (0.26)]. Across-task variability may
      be a sensitive marker of cognitive decline in individuals with prodromal HD
      approaching disease onset. However, individual neuropsychological tasks,
      including a measure of within-task variability, produced larger effect sizes than
      an index of across-task IIV in this sample.

PMID- 26304061
TI  - Epicutaneous immunotherapy with a hypoallergenic Bet v 1 suppresses allergic
      asthma in a murine model.
AB  - BACKGROUND: Due to reduced allergic potency, hypoallergenic variants have been
      suggested as safer and potentially more efficacious alternative to the
      corresponding wild-type allergens in allergen-specific immunotherapy. Here, we
      aimed at investigating the efficacy of recombinant Bet v 1B2, a hypoallergenic
      folding variant of Bet v 1, in epicutaneous immunotherapy to suppress asthmatic
      features using a murine model of birch pollen allergy. METHODS AND RESULTS:
      Before, or after sensitization with rBet v 1 plus ALUMW and intranasal challenges
      with birch pollen extract, BALB/c mice received epicutaneous immunization (EPI)
      with rBet v 1, or rBet v 1B2 on their depilated back. Prophylactic EPI with rBet
      v 1B2, but not with rBet v 1, suppressed serum levels of Bet v 1-specific IgE
      antibodies and reduced the number of eosinophils and the concentrations of Th2
      cytokines in bronchoalveolar lavage. In an established allergic condition, serum
      levels of Bet v 1-specific IgE antibodies were similar between PBS-treated
      control mice and EPI-treated mice. However, therapeutic EPI with rBet v 1B2, but
      not with rBet v 1, significantly suppressed the development of airway
      inflammation and lung function impairment. CONCLUSION: This study is the first to
      show the effect of therapeutic EPI with a recombinant form of a hypoallergenic
      folding variant on the suppression of asthmatic features. Our results suggest
      that rBet v 1B2 along with its reduced IgE-binding capacity could be a preferred
      therapeutic allergen than wild-type rBet v 1 in epicutaneous immunotherapy of
      birch pollen-induced allergic asthma, in particular due to a lower risk of
      allergic side effect.

PMID- 26304062
TI  - Comparative Effectiveness of Biomarkers to Target Cancer Treatment: Modeling
      Implications for Survival and Costs.
AB  - BACKGROUND: Biomarkers used at the time of diagnosis to tailor treatment
      decisions may diffuse into clinical practice before data become available on
      whether biomarker testing reduces cancer mortality. In the interim, quantitative
      estimates of the mortality impact of testing are needed to assess the value of
      these diagnostic biomarkers. These estimates are typically generated by
      customized models that are resource intensive to build and apply. METHODS: We
      developed a user-friendly system of models for Cancer Translation of Comparative
      Effectiveness Research (CANTRANce) to model the mortality impact of cancer
      interventions. The Diagnostic Biomarker module of this system projects the
      mortality impact of testing for a diagnostic biomarker, given data on how testing
      affects treatment recommendations. Costs and quality-of-life outcomes may also be
      modeled. We applied the Diagnostic Biomarker module to 2 case studies to
      demonstrate its capabilities. RESULTS: The user interface
      (http://www.fhcrc.org/cantrance) allows comparative effectiveness researchers to
      use the Diagnostic Biomarker module of CANTRANce. Our case studies indicate that
      the model produces estimates on par with those generated by customized models and
      is a strong tool for quickly generating novel projections. LIMITATIONS: The
      simple structure that makes CANTRANce user-friendly also constrains the
      complexity with which cancer progression can be modeled. The quality of the
      results rests on the quality of the input data, which may pertain to small or
      dissimilar populations or suffer from informative censoring. CONCLUSIONS: The
      Diagnostic Biomarker module of CANTRANce is a novel public resource that can
      provide timely insights into the expected mortality impact of testing for
      diagnostic biomarkers. The model projections should be useful for understanding
      the long-term potential of emerging diagnostic biomarkers.

PMID- 26304063
TI  - Informed Decision Making: Assessment of the Quality of Physician Communication
      about Prostate Cancer Diagnosis and Treatment.
AB  - INTRODUCTION: Little is known about how physicians present diagnosis and
      treatment planning in routine practice in preference-sensitive treatment
      decisions. We evaluated completeness and quality of informed decision making in
      localized prostate cancer post biopsy encounters. METHODS: We analyzed audio
      recorded office visits of 252 men with presumed localized prostate cancer
      (Gleason 6 and Gleason 7 scores) who were seeing 45 physicians at 4 Veterans
      Affairs Medical Centers. Data were collected between September 2008 and May 2012
      in a trial of 2 decision aids (DAs). Braddock's previously validated Informed
      Decision Making (IDM) system was used to measure quality. Latent variable models
      for ordinal data examined the relationship of IDM score to treatment received.
      RESULTS: Mean IDM score showed modest quality (7.61+/-2.45 out of 18) and high
      variability. Treatment choice and risks and benefits were discussed in
      approximately 95% of encounters. However, in more than one-third of encounters,
      physicians provided a partial set of treatment options and omitted surveillance
      as a choice. Informing quality was greater in patients treated with surveillance
      (beta = 1.1, p = .04). Gleason score (7 vs 6) and lower age were often cited as
      reasons to exclude surveillance. Patient preferences were elicited in the
      majority of cases, but not used to guide treatment planning. Encounter time was
      modestly correlated with IDM score (r = 0.237, p = .01). DA type was not
      associated with IDM score. DISCUSSION: Physicians informed patients of options
      and risks and benefits, but infrequently engaged patients in core shared decision
      making processes. Despite patients having received DAs, physicians rarely
      provided an opportunity for preference-driven decision making. More attention to
      the underused patient decision-making and engagement elements could result in
      improved shared decision making.

PMID- 26304064
TI  - Does Introducing Imprecision around Probabilities for Benefit and Harm Influence
      the Way People Value Treatments?
AB  - BACKGROUND: Imprecision in estimates of benefits and harms around treatment
      choices is rarely described to patients. Variation in sampling error between
      treatment alternatives (e.g., treatments have similar average risks, but one
      treatment has a larger confidence interval) can result in patients failing to
      choose the option that is best for them. The aim of this study is to use a
      discrete choice experiment to describe how 2 methods for conveying imprecision in
      risk influence people's treatment decisions. METHODS: We randomized a
      representative sample of the Canadian general population to 1 of 3 surveys that
      sought choices between hypothetical treatments for rheumatoid arthritis based on
      different levels of 7 attributes: route and frequency of administration, chance
      of benefit, serious and minor side effects and life expectancy, and imprecision
      in benefit and side-effect estimates. The surveys differed in the way imprecision
      was described: 1) no imprecision, 2) quantitative description based on a range
      with a visual graphic, and 3) qualitative description simply describing the
      confidence in the evidence. RESULTS: The analyzed data were from 2663
      respondents. Results suggested that more people understood imprecision when it
      was described qualitatively (88%) versus quantitatively (68%). Respondents who
      appeared to understand imprecision descriptions placed high value on increased
      precision regarding the actual benefits and harms of treatment, equivalent to the
      value placed on the information about the probability of serious side effects.
      Both qualitative and quantitative methods led to small but significant increases
      in decision uncertainty for choosing any treatment. Limitations included some
      issues in defining understanding of imprecision and the use of an internet survey
      of panel members. CONCLUSIONS: These findings provide insight into how conveying
      imprecision information influences patient treatment choices.

PMID- 26304065
TI  - ELASTOGRAPHIC EVALUATION OF NATURALLY OCCURING TENDON AND LIGAMENT INJURIES OF
      THE EQUINE DISTAL LIMB.
AB  - Compression elastography is an ultrasonographic technique that estimates tissue
      strain and may have utility in diagnosing and monitoring soft tissue injuries in
      the equine athlete. Recently, elastography has been proven to be a feasible and
      repeatable imaging modality for evaluating normal tendons and ligaments of the
      equine distal forelimb. The purposes of this prospective study were to
      investigate the ability of elastography to detect spontaneously occurring lesions
      of equine tendons and ligaments diagnosed with magnetic resonance imaging (MRI)
      and gray-scale ultrasound (US) and to characterize the differences in the
      elastographic appearance of acute vs. chronic injuries. Fifty seven horses with a
      total of 65 lesions were evaluated. Images were assessed quantitatively and
      qualitatively. Acute lesions were found to be significantly softer (P < 0.0001)
      than chronic lesions (P < 0.0001) and the stiffness of lesions increased with
      progression of healing (P = 0.0138). A negative correlation between lesion
      hypoechogenicity and softness was appreciated with more hypoechoic lesions
      appearing softer (P = 0.0087) and more hyperechoic regions harder (P = 0.0002). A
      similar finding occurred with increased signal intensity on short tau inversion
      recovery (STIR) and proton density (PD) MRI sequences correlating with increased
      softness on elastography (P = 0.0164). Using US and MRI as references, commonly
      encountered soft tissue injuries of the equine distal limb could be detected with
      elastography. However, elastography was limited for detecting small, proximal
      injuries of the hindlimb proximal suspensory ligament. Elastographic evaluation
      of equine tendons and ligaments may allow better characterization of lesion
      chronicity and severity, and sequential examinations may optimize lesion
      management, rehabilitation, and return to training. 

PMID- 26304066
TI  - Transgenerational effects of a hypercaloric diet.
AB  - The effects of a maternal hypercaloric diet (HD) during puberty and early
      adulthood on neuroimmune aspects in offspring were investigated. In female rats
      of the F0 generation and male rats of the F1 generation, bodyweight (BW) gain,
      retroperitoneal fat (RPF) weight, the number of hypodermic adipocytes (HAs) and
      expression of glial fibrillary acidic protein (GFAP) were measured in
      hypothalamic astrocytes. On Postnatal Day 50, the F1 pups were challenged with
      lipopolysaccharide (LPS, 100ugkg-1, s.c.) or an equal volume of saline (S), and
      behaviour in the open field test was evaluated, as were plasma neuropeptide and
      cytokine concentrations. The maternal HD caused the female F0 rats to become
      overweight. The F1 offspring of dams fed the HD and challenged with saline (HDS
      group) exhibited increases in BW gain, RPF weight and in the number of large HAs
      and a decrease in GFAP immunoreactivity. F1 offspring of dams fed the HD and
      challenged with LPS (HDLPS group) exhibited decreases in BW gain, RPF weight and
      GFAP immunoreactivity, but no differences were observed in the number of larger
      and small HAs. Plasma tumour necrosis factor-alpha concentrations were high in
      the HDS and HDLPS groups. Thus, the maternal HD during puberty and early
      adulthood caused the F1 generation to become overweight despite the fact that
      they received a normocaloric diet. These results indicate a transgenerational
      effect of the HD that may occur, in part, through permanent changes in immune
      system programming. The attenuation of neuroinflammation biomarkers after LPS
      administration may have resulted in a decrease in the number of adipocytes,
      which, in turn, reduced cytokine, adipokine and chemokine levels, which are able
      to recruit inflammatory cells in adipose tissue.

PMID- 26304067
TI  - Mutational and functional analysis of Glucose transporter I deficiency syndrome.
AB  - OBJECTIVE: We investigated a correlation between a mutation in the SLC2A1 gene
      and functional disorders in Glucose transporter I deficiency syndrome (GLUT1DS).
      METHODS: We performed direct sequence analysis of SLC2A1 in a severe GLUT1DS
      patient and identified a novel frame shift mutation, c.906_907insG, p.V303fs. We
      created a plasmid vector carrying the c.906_907insG mutation, as well as A405D or
      R333W in the SLC2A1, which are found in patients with mild and moderate GLUT1DS
      severity, respectively. We transiently expressed these mutants and wild type
      SLC2A1 plasmids in a human embryonic kidney cell line (HEK293), and performed
      immunoblotting, immunofluorescence, and enzymatic photometric 2-deoxyglucose
      (2DG) uptake assays. RESULTS: GLUT1 was not detected after transient expression
      of the SLC2A1 plasmid carrying c.906_907insG by either immunoblotting or
      immunofluorescence. The degree of glucose transport reduction as determined by
      enzymatic photometric 2DG assay uptake correlated with disease severity.
      CONCLUSIONS: Enzymatic photometric 2DG uptake study appears to be a suitable
      functional assay to predict the effect of SLC2A1 mutations on GLUT1 transport.

PMID- 26304068
TI  - Letter to the editor.

PMID- 26304069
TI  - Massive ischemic stroke as a complication of otitis media.
AB  - Cerebral artery infarction as a complication of acute otitis media is a rare
      complication. The mechanism appears to be the spread of meningeal inflammation to
      involve the walls of intracranial vessels, resulting in arterial thrombosis with
      ischemia or rupture with hemorrhage. We report the case of a 3 year old female
      with a history of global developmental delay who sustained a large left
      hemispheric stroke after middle cerebral artery infarction as a complication of
      an acute otitis media. 

PMID- 26304070
TI  - Pediatric sinogenic epidural and subdural empyema: The role of endoscopic sinus
      surgery.
AB  - AIM: To analyze the indications and outcomes of open neurosurgical approaches
      (ONA) and endoscopic transnasal approaches (ETA) in the surgical management of
      pediatric sinogenic subdural and epidural empyema. MATERIAL AND METHODS:
      Retrospective single-center study design within a tertiary care referral center
      setting. Children less than 18 years of age consecutively operated on between
      January 2012 and February 2014 for drainage of a sinogenic subdural empyema (SE)
      or epidural (EE) empyema were included. MAIN OUTCOME MEASURES: success of first
      surgical procedure, persistent symptoms and sequelae at the end of the follow-up
      period. RESULTS: Nine SE (53%) and 8 EE (47%) were observed. Neurological
      symptoms, especially seizures, were more frequent in the SE group. Perioperative
      pus samples were positive in 67% of the SE group and in 75% of the EE group. The
      most frequently isolated bacteria belonged to the Streptococcus anginosus group.
      CT or MR imaging showed that most empyema probably originated from the frontal
      sinus. However, two cases resulted from an ethmoiditis and one case from a Pott's
      puffy tumor, without any direct contact with the paranasal sinus. In cases of SE,
      the most effective surgical technique was ONA with craniotomy. Associated
      endoscopic sinus drainage was useful for the purpose of bacteriological
      diagnosis. In cases of EE, effectiveness was noted in both ONA and ETA
      techniques. In two cases of EE, the ETA procedure encompassed direct drainage of
      the empyema through the posterior wall of the frontal sinus (Draf III approach).
      The number of patients successfully treated after a single surgical procedure was
      higher in the EE group (p=0.05). Regarding outcomes, no mortalities were
      observed. Persistent disorders at the end of the follow-up period, especially
      headaches, cognitive, concentration or schooling problems, tended to be more
      frequent in the SE group than in the EE group (67% vs 29%), and were more
      commonly observed in cases requiring several surgical procedures (75% vs 12.5%)
      (p=0.05). DISCUSSION: Endoscopic sinus surgery plays a critical role in the
      surgical management of pediatric sinogenic SE and EE. In cases of small volume
      EE, the endoscopic approach associated with antibiotherapy may be sufficient to
      treat the infectious process.

PMID- 26304072
TI  - [To implement prophylactic treatment and improve the quality of life in patients
      with hemophilia in China].

PMID- 26304071
TI  - Guiding health care transformation: A next-generation, diagnostic remediation
      tool for leveraging polarities.
AB  - BACKGROUND: Health care reform is optimized through the Polarity Thinking Model
      to achieve and sustain improvements in cost, safety, quality, and efficiency.
      Traditional problem-solving "fix-it" approaches have histories of inadequacy and
      failure in addressing the multiple polarities inherent in health care
      transformation. The Polarity Thinking Model is reviewed followed by a study
      conducted to establish validity and reliability for diagnostic assessment and
      remediation through leveraging polarities. METHODS: Thirteen common health care
      polarities were identified by an International Consortium, each needing to be
      leveraged or managed within an organization engaged in health care
      transformation. A Web-based survey tool was designed to provide leaders with
      readily interpretable diagnostic information for organizational evaluation
      regarding how well each polarity is being managed. Four hundred ninety-seven
      volunteers from two American and two Canadian acute care organizations
      participated. RESULTS: Content and context validity were established, and
      statistically significant reliabilities for the survey instrument were verified.
      Interpretations of study findings verify the assessment accuracy and interpretive
      value of the information for leading organizational optimization. CONCLUSIONS:
      Employing the Polarity Thinking Model and tools to evaluate how well
      organizations are managing polarities will enhance the organization's ability to
      self-diagnose and then succeed in achieving transformation toward sustainable
      desired outcomes.

PMID- 26304073
TI  - [The guidelines for absolute count of CD34+ cell determination by flow
      cytometry].

PMID- 26304074
TI  - [A case report of gastric cancer complicated with chronic lymphocytic leukemia].

PMID- 26304075
TI  - [Efficacy and safety of anagrelide in treatment of essential thrombocythemia:
      multicenter, randomized controlled clinical trial].
AB  - OBJECTIVE: To evaluate the efficacy and safety of anagrelide in essential
      thrombocythemia (ET). METHODS: Patients who diagnosed as ET according to the
      World Health Organization classification were enrolled. Each patient was assigned
      to take anagrelide hydrochloride capsule or hydroxyurea tablet by random 1?1
      ratio. Dose of anagrelide started at 2 mg/d, then increased gradually and the
      maximum dose was 10 mg/d until the platelet counts dropped to (100-400) * 109/L,
      one month later gradually reduced to maintain dose. The dose of hydroxyurea was
      1000 mg/d at beginning, then increased gradually, when platelet counts dropped to
      (100-400)*109/L and kept for one month, reduced to maintain dose as 10 mg.kg-1.d
      1. The observation period was 12 weeks. RESULTS: A total of 222 patients were
      enrolled in seventeen centers (including 113 patients treated with anagrelide and
      109 with hydroxyurea). Therapy efficacy can be evaluated in 198 patients
      (including 97 patients administered with anagrelide and 101 with hydroxyurea). At
      12th weeks of therapy, the hematologic remission rate was 87.63% (85/97) in
      anagrelide group and 88.12% (89/107) in hydroxyurea group, the differences
      between the two groups were not significant (P=0.173). Treatment with anagrelide
      lowered the platelet counts by a median of 393 (362-1 339) * 109/L from a median
      of 827 (562-1657) * 109/L at the beginning of the observation to 400(127
      1130)*109/L after 12 weeks (P<0.001), which were similar to the treatment result
      of hydroxyurea by a median drop of 398 (597-1846)* 109/L (P=0.982). The median
      time to achieving response of anagrelide group was 7 (3-14) days, superior to
      that of hydroxyurea for 21 (14-28) significantly (P=0.003). Frequency of
      anagrelide related adverse events was 65.49 % (74/113), including cardiopalmus
      (36.28% ), headache (21.24% ), fatigue (14.16% ) and dizzy (11.50% ). CONCLUSION:
      Anagrelide was effective in patients with ET which had similar hematologic
      remission rate to hydroxyurea and could take effect more quickly than
      hydroxyurea. Incidence of adverse events was undifferentiated between anagrelide
      and hydroxyurea, but anagrelide treatment had tolerable adverse effects and no
      hematologic toxicity.

PMID- 26304076
TI  - [The prognostic value of early BCR-ABL transcripts level in 251 patients with
      chronic myeloid leukemia after treatment with imatinib].
AB  - OBJECTIVE: To understand the prognostic value of early monitoring BCR-ABL
      transcripts in patients with chronic myeloid leukemia (CML) after treatment with
      imatinib, and to provide the information for early assessment of prognosis and
      treatment options. METHODS: The clinical data of 251 patients with CML in chronic
      phase (CML-CP) who received imatinib as first-line therapy were retrospectively
      analyzed, the progression-free survival (PFS)and overall survival (OS) between
      different BCR-ABL transcriptional level at 3 and 6 month after imatinib treatment
      were compared. Meanwhile, Chi-square test and logistic regression were used to
      analyze the risk factors for disease progression. RESULTS: At 3 months after
      imatinib treatment BCR-ABL transcriptional levels>10%, >1%-<= 10% and <= 1% were
      found in 92, 94 and 64 patients, their PFS were 53.3%, 71.3% and 86.2%,
      respectively. The results showed that the PFS of patients with low BCR-ABL
      transcriptional levels was significantly superior to that with high BCR-ABL
      transcriptional levels for CML at 3 months treatment (P<0.05). The OS of three
      group did not reach statistical significance (92.4% vs 96.8% vs 93.8%, P> 0.05).
      When 182 patients received imatinib treatment at 6 months, 22 patients with BCR
      ABL transcriptional levels>10%, 50>1% -<= 10% and 110 <= 1%, their PFS were 27.3%
      vs 66.0% vs 82.7% (P<0.05), the OS of three groups were 86.4% vs 94.0% vs 100%.
      There were significant differences among the three groups (P<0.05). Logistic
      regression confirmed that the level of BCR-ABL transcriptional level at 3 and 6
      months after imatinib treatment was independent factor to influence the progress
      of disease. CONCLUSION: It is important for the prognosis evaluation of CML
      patients to monitor BCR-ABL transcriptional level at 3 and 6 months after
      imatinib treatment.

PMID- 26304077
TI  - [Identification of a novel aberrant spliceosome of MPL gene (MPLL391-V392ins12)in
      patients with myeloproliferative neoplasms].
AB  - OBJECTIVE: To identify the MPL L391-V392ins12 spliceosome and analyze its
      frequencies in patients with myeloproliferative neoplasms (MPN). METHODS: MPL
      aberrant spliceosome was identified through reverse transcription polymerase
      chain reaction (RT-PCR)combined with cloning sequencing. The mutation of this
      spliceosome in 248 MPN patients and 200 normal people was determined by allele
      specific polymerase chain reaction (AS-PCR). RESULTS: A novel aberrant
      spliceosome of MPL gene (MPL L391-V392ins12)was identified, i.e. 36 bp intron was
      retained between exon7 and exon8, and there were 12 amino acids
      (EGLKLLPADIPV)inserted. MPL L391-V392ins12 mutation was detected in 19 (7.66%)of
      the 248 patients with MPN, including 1 (1.92%) of 52 patients with PV, 14 (9.66%)
      of 145 with ET, and 4 (7.84%) of 51 with PMF. And the mutation was not detected
      in the group of 200 normal people. CONCLUSION: MPL L391-V392ins12 spliceosome is
      an aberrant spliceosome present in the MPN. It can be detected in PV, ET and PMF,
      and more frequently in ET and PMF. This mutation may play an important role in
      the process of MPN.

PMID- 26304078
TI  - [In vitro study of BRD4 inhibitor GSK525762A against primary adult common B-cell
      acute lymphoblastic leukemia cells in vitro].
AB  - OBJECTIVE: To investigate the effects of bromodomain-containing protein 4 (BRD4)
      inhibitor GSK525762A on the proliferation and apoptosis of primary common B-cell
      acute lymphoblastic leukemia (common B-ALL) cells from adult patients, then to
      further explore the possible mechanisms. METHODS: Purified leukemia cells from 14
      common B-ALL adult patients (4 Ph+ and 10 Ph- cases) were obtained by flow
      cytometry sorting, and maintained in a mimic bone marrow microenvironment culture
      system for short-term culture. Leukemia cells were treated with various
      concentrations of GSK525762A. The inhibitory effects of BRD4 inhibitor on common
      B-ALL leukemia cells were measured by CCK-8 assay and the apoptosis of those
      cells was determined by AnnexinV/7-AAD staining using flow cytometry. The
      transcripts of c-MYC, CDK6 and Bcl-2 were detected by quantitative RT-PCR, and
      the expression of c-MYC, CDK6 and Bcl-2 proteins were detected via Western blot.
      RESULTS: GSK525762A could inhibit the proliferation of leukemia cells from all 14
      common B-ALL patients in a dose-dependent manner, the median value of IC50 was
      256.25 (90.64-1 378.39)nmol/L. GSK525762A could promote cells apoptosis of B-ALL
      leukemia cells in a dose-dependent manner, the median apoptosis rates
      respectively were 45.17%(9.38%-70.91%), 66.02% (24.36%-96.34%) and 89.29% (39.29%
      99.37%) after treated by 500, 1 000 and 2 500 nmol/L GSK525762A. GSK525762A has a
      similar effect on Ph+ ALL and Ph- B-ALL, but the effect of proliferation
      inhibition and apoptosis enhancement on Ph+ B-ALL is weaker than that on Ph- B
      ALL. Compared with vehicle control group, the levels of c-MYC, Bcl-2 and CDK6
      transcripts in leukemic cells were reduced after treatment for 24 h and 48 h by 1
      000 nmol/L GSK525762A, and there are no significant differences in the
      downregulation of c-MYC and CDK6 mRNA between Ph+ and Ph- B-ALL; however, the
      inhibitory effect on Bcl-2 transcription was weaker in Ph+ B-ALL cells than that
      in Ph- B-ALL cells. Moreover, c-MYC, Bcl-2 and CDK6 protein levels decreased in
      GSK525762A treated group. CONCLUSION: GSK525762A could strongly inhibit the
      proliferation of common B-ALL and trigger apoptosis; meanwhile it has certain
      effects against Ph+ ALL in vitro. The effect may be achieved by down-regulation
      of c-MYC, CDK6 and Bcl-2 expression.

PMID- 26304079
TI  - [A case report of childhood acute lymphoblastic leukemia with intrachromosomal
      amplification of AML1 gene in chromosome 21 and TEL deletion].

PMID- 26304080
TI  - [The effect of up-regulated expression of Rap1GAP on the invasion ability of HL
      60 cells in vitro and in vivo].
AB  - OBJECTIVE: To investigate the effect of up-regulation of Rap1GAP on the invasion
      ability of leukemic HL-60 cells in vitro, and to establish leukemia mouse model
      to verify the effects in vivo. METHODS: Quantitative RT-PCR and Western blot
      methods were used to detect the expression of Rap1GAP in Venus/HL-60 (vehicle
      control) and Rap1GAP/HL-60 cells (R1 andR2). Transwell method was used to examine
      the invasion ability in vitro. Quantitative RT-PCR and gelatin zymograph were
      used to study the expression of MMP-2 and MMP-9. Four-week-old BALB/c nu/nu mice
      were pre-treated and inoculated with leukemic cells from different groups,
      several index including survival time were then monitored. RESULTS: Rap1GAP mRNA
      level of R1 and R2 increased about 16-17 folds as compared to the control cells.
      The invasion rate of R1 and R2 are (55 +/- 5)% and (59 +/- 4)%, which are
      significantly higher than (14 +/- 4)% of the control cells. The mRNA level of MMP
      9 was up-regulated about 12.0 folds in R1 and R2 cells compared to the
      corresponding control cells. The median survival times of R1 and R2 mice are
      (32.00 +/- 1.85) d and (33.37 +/- 2.50) d, respectively, which are shorter than
      (43.62 +/- 2.32) d of the control group. Three mice of R1 and R2 groups showed
      leukemic cells infiltration in meninges tissue, and the genes of Rap1GAP and MMP
      9 were amplified by PCR method. CONCLUSION: Up-regulated expression of Rap1GAP
      increased the invasion ability of HL-60 cells accompanied with enhancement of MMP
      9 expression in vitro, and the experiment in mouse model also confirmed that
      Rap1GAP enhanced the invasion of HL-60 cells in vivo.

PMID- 26304081
TI  - [Effect of brentuximab vedotin combined with chlormethine hydrochloride on the
      treatment of 6 patients with relapsed and refractory Hodgkin lymphoma].
AB  - OBJECTIVE: To observe the clinical efficacy and side effects of brentuximab
      vedotin (BV) plus chlormethine hydrochloride (CH) in patients with relapsed and
      refractory Hodgkin lymphoma (HL) after failure with BV alone. METHODS: From
      March, 2014 to December, 2014, 6 patients who failed with BV monotherapy were
      enrolled in this study. The chemotherapy regimen consisted of BV (1.2-1.8 mg/kg,
      iv. gtt, d1) and CH (6 mg/m2, iv. gtt, d1) was given for 3 weeks as one course,
      and all patients received about 3-8 courses of chemotherapy, with an median of 4
      courses. Clinical efficacy and adverse events were assessed and observed by
      radiographic examination and serological detection. RESULTS: Among 6 patients,
      the overall response rate was 100% with 2 complete remission and 4 partial
      remission. The main adverse events were grade I (2 patients) and IV (2 patients)
      bone marrow depression, grade II (2 patients)gastrointestinal reaction, grade I
      (1 patient) increase of transaminase and myocardial enzyme and grade I (1
      patient) mouth ulcers. CONCLUSION: The combination of BV and CH in the treatment
      of relapsed and refractory HL after failure with BV alone was high effective and
      the toxicities were well tolerable.

PMID- 26304082
TI  - [Rituximab combined with second line regimens for treatment of seven relapsed and
      refractory Hodgkin lymphoma patients].
AB  - OBJECTIVE: To investigate the efficacy and safety of Rituximab combined with
      second line regimen for treatment of relapsed and refractory Hodgkin lymphoma.
      METHODS: Seven patients with relapsed and refractory Hodgkin lymphoma were
      treated with Rituximab combined with second line regimen. Among them, two
      patients were treated with R-GDP (E) [rituximab, gemcitabine, cisplatin,
      dexamethasone (etoposide)] regimen, another two patients with R-IGVP (rituximab,
      ifosfamide, gemcitabine, vinorelbine, prednisone)regimen, and the left three
      patients with R-BEACOPP (rituximab, bleomycin, etoposide, doxorubicin,
      cyclophosphamide, vincristine, procarbazine, prednisone)regimen. The efficacy and
      safety were evaluated during and after chemotherapy. RESULTS: There're three male
      and four female patients, whose median age was 21 years (range 12-36 years) old.
      One patient was diagnosed as nodular lymphocyte-predominant Hodgkin lymphoma
      (NLPHL), and the other six patients as classical HL (four nodular sclerosis HL,
      one lymphocyte-rich classical HL and one hmixed cellularity HL). The median
      cycles of salvage therapy were 4(1-4), and the median follow-up was 29 months (24
      58 months). Among these 7 patients, the complete remission was observed in 4
      patients, stable disease in 2 patients, but one patient died during salvage
      therapy. The two-year survival rates were 85.7% and the major toxic effects were
      bone marrow suppression. CONCLUSION: These results indicate that the Rituximab
      combined with second line regimen is an effective therapy for relapsed and
      refractory Hodgkin lymphoma.

PMID- 26304083
TI  - [Efficacy observation of tigecycline in the treatment of 107 patients with
      infection due to granulocytopenia].
AB  - OBJECTIVE: To observe the curative effect and side effect of tigecycline in the
      treatment of patients with infection caused by granulocytopenia. METHODS: The
      clinical data of 107 patients who were treated with tigecycline for infection due
      to granulocytopenia were retrospectively reviewed. The tigecycline was
      administered by intravenously (30-60 min drip infusion)as the initial dose of 100
      mg and maintenance does of 50 mg, every 12h. The whole treatment course kept for
      5-7 d when the body temperature was normal and then the step-down treatment or
      discontinuation of the drug was adopted. RESULTS: A total of 104 strains of
      bacteria were isolated from 107 cases of hospitalized patient, including 60 multi
      drug resistant strains (MDR) and 2 extensively-drug resistant strains (XDR). The
      total effective rate of tigecycline treatment was 62.6%, including 30 cases with
      tigecycline alone (63.3% of the effective rate), 21 cases with tigecycline as
      initial treatment followed by combination with other antibiotics (61.9% of the
      effective rate), and 56 cases with tigecycline in combination with other
      antibiotics from the beginning of the treatment (62.5% of the effective rate).
      There was no statistical significant difference between the 3 treatment groups
      (P=0.994). Among the 39 patients with MDR strains, 22 patients' temperature was
      controlled , 9 patients died, and 8 patients' temperature remained uncontrolled.
      The clinical effective rate of these patients was 56.4%. The median onset time of
      tigecycline treatment was 3 days. The adverse drug reactions of nausea (11.2% )
      and vomiting (8.4% )were tolerable. CONCLUSION: Tigecycline is effective in
      treatment of resistant bacteria infection in patients with granulocytopenia. The
      side effects of tigecycline were few, safe and generally well tolerated.

PMID- 26304084
TI  - [Outcomes of adults with Ph-negative B-cell acute lymphoblastic leukemia after
      autologous hematopoietic stem cell transplantation and the significance of
      minimal residual disease].
AB  - OBJECTIVE: To better understand predictive factors and role of autologous
      hematopoietic stem cell transplantation (auto-HSCT)in the post-remission therapy
      for adult Ph-negative B-cell acute lymphoblastic leukemia (B-ALL)patients.
      METHODS: Outcomes of 86 adult patients with B-ALL who received auto-HSCT in our
      center from January 1996 to February 2014 were retrospectively analyzed. RESULTS:
      Overall survival (OS)and disease free survival (DFS)at 5 years for the cohort
      were (63.8 +/- 5.6)% and (60.9 +/- 5.6)%, respectively. The cumulative non
      relapse mortality (NRM)and relapse at 5 years were (4.70 +/- 0.05)% and (34.40 +/
      0.31)%. For DFS, age >= 35 years, high lactate dehydrogenase at diagnosis, high
      initial WBC count, blast cell proportion >= 5% on 15th day of the first induction
      therapy, complete remession (CR)1 to HSCT interval >6 months and CD34+ cells in
      graft >= 3.8 * 106/kg were the poor prognostic factors. CR1 to HSCT interval >6
      months was the independently undesirable factors in COX regression model. For 34
      patients who had results of minimal residual disease (MRD), positive
      pretransplantation MRD (MRD>=0.01%), positive post-induction MRD or MRD positive
      again during the chemotherapy indicated poor prognosis, and the last one was the
      independent adverse prognostic factor. CONCLUSION: Auto-HSCT combined with post
      transplantation maintenance chemotherapy could be an optional approach for adult
      B-ALL patients. MRD plays a significant role in the treatment choice for adult Ph
      negative B-ALL patients.

PMID- 26304085
TI  - [Efficacy comparison between Ph+ ALL patients treated with chemotherapyplus
      tyrosine kinase inhibitors followed by allo-HSCT and Ph-ALL patients with allo
      HSCT: a case control study from a single center].
AB  - OBJECTIVE: To compare the efficacy of the Ph+ acute lymphoblastic leukemia
      (ALL)patients treated with combination of tyrosine kinase inhibitors (TKI)and
      chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo
      HSCT) and Ph- ALL patients with allo-HSCT. METHODS: A total of 19 Ph+ALL patients
      were matched with 19 Ph-ALL patients from 55 B-ALL patients receiving allo-HSCT
      in our hospital between January 2003 and August 2014 and were analyzed
      retrospectively. RESULTS: Gender, median age, number of patients with blood white
      count more than 30 * 109/L, number of patients with meningeal leukemia, disease
      status before allo-HSCT, period of allo-HSCT, the source of stem cell from
      donors, HLA disparities between donor and recipient, conditioning regimens and
      number of infused mononuclear cells and CD34+ cells were comparable between two
      groups of Ph+ and 19 Ph-ALL patients. The median time of engraftment of
      neutrophil cells was 12 days versus 13 days (P= 0.284) and that of platelet 14
      days versus 17 days (P=0.246), which were comparable between two groups. The
      estimated 3-year overall survival (OS) in Ph+ and Ph-ALL groups was (67.5 +/-
      12.4)% versus (74.3 +/- 11.4)% (P=0.434) and 3-year disease free survival
      (DFS)was (67.8 +/- 12.4)% versus (74.3 +/- 11.4)% (P= 0.456), respectively. The
      cumulative incidence of degree II-IV acute graft-versus-host disease (aGVHD)in
      Ph+ and Ph- ALL group was (15.8+/-8.4)% versus (21.1 +/- 9.4)% (P=0.665)and that
      of degree III-IV aGVHD was (5.6 +/- 5.4)% versus (11.5 +/- 7.6)% (P=0.541),
      respectively. The cumulative incidence of cGVHD was (44.1 +/- 14.0)% in Ph+ALL
      group versus (44.1 +/- 13.0)% in Ph-ALL group (P=0.835) and that of extensive
      cGVHD was (13.1 +/- 8.7)% versus (6.2 +/- 6.1)% (P=0.379), respectively. The
      cumulative relapse rate and the cumulative non-relapse rate in both group also
      have no statistical difference [(10.8 +/- 7.2)% versus (20.0 +/- 10.7)% (P=0.957)
      and (23.9 +/- 12.4)% versus (7.1+/-6.9)% (P=0.224), respectively]. CONCLUSION:
      The efficacy of Ph+ALL treated with combination of chemotherapy and TKIs and
      followed by allo-HSCT is comparable to that of Ph-ALL with allo-HSCT.

PMID- 26304086
TI  - [Flow cytometric test using eosin-5'-maleimide (EMA) labelling of red blood for
      diagnosis of hereditary spherocytosis].
AB  - OBJECTIVE: To investigate the sensitivity and specificity of eosin-5'-maleimide
      (EMA)assay for the diagnosis of hereditary spherocytosis (HS), and to verify the
      stability of reagent and samples. METHODS: EMA flow cytometry test, NaCl-osmotic
      fragility test and acidified glycerol lysis test were performed using peripheral
      blood samples from 80 patients with HS and 44 patients with other blood diseases,
      the sensitivity and specificity of the three methods were compared, and the
      feasibility of EMA binding test was estimated. The stability of EMA reagent and
      HS samples stored at different temperatures were tested. RESULTS: Among the 124
      tested samples, the sensitivity and specificity of EMA binding test was 0.925 and
      0.954, that of NaCl-osmotic fragility test was 0.950 and 0.455, and that of
      acidified glycerol lysis test was 1.000 and 0.318, respectively. Although the
      sensitivity of NaCl-osmotic fragility test and acidified glycerol lysis test was
      a little higher than that of EMA binding test, the specificity of the former two
      methods was poor, they couldn't clearly distinguish whether spherocytosis is
      hereditary spherocytosis. The experiment results showed that EMA was sensitive to
      the temperature and should not be stored in a small aliquots at -80 C over a
      period of 6 months. The stability of the HS sample was better, 6 days storage at
      4 C and 3 days storage at room temperature had no influence on the results.
      CONCLUSION: EMA binding test by flow cytometry showed good sensitivity and
      specificity for HS diagnosis. EMA reagent should be stored at-80 C and the HS
      samples should be tested within 6 days storage at 4 C and 3 days at room
      temperature.

PMID- 26304087
TI  - [Inhibitory effect of von Willebrand factor-cleaving protease on angiogenesis].
AB  - OBJECTIVE: To investigate the inhibitory effect of von Willebrand factor-cleaving
      protease, a disintegrin-like and metalloprotease with thrombospondin-1 repeats
      (ADAMTS13)on angiogenesis induced by vascular endothelial growth factor (VEGF)in
      vitro and in vivo. METHODS: Cell proliferation assay, differentiation (tube
      formation)assay and wound migration assay were performed by using human umbilical
      vein endothelial cells (HUVECs)to explore the effect of ADAMTS13 on angiogenesis
      in vitro. Cells were treated with different concentrations of ADAMTS13 (1, 5, 25,
      50 and 100 nmol/L)and the number of cells was counted via MTT assay. In addition,
      effect of ADAMTS13 on differentiation was assessed by measuring the length of
      capillary-like tube structures formed by HUVECS in matrigel. Effect of ADAMTS13
      on HUVEC migration was assessed via calculation of wound healing distance after 8
      hrs culture with VEGF or ADAMTS13. Chick embryo chorioallantoic membrane (CAM)
      assay and Matrigel plug assay were performed to investigate the effect of
      ADAMTS13 on angiogenesis in vivo. RESULTS: ADAMTS13 significantly inhibited the
      proliferation of HUVECs induced by VEGF in a dose-dependent manner. Migration
      distance of HUVECs was (79 +/- 22) MUm in control group, (250 +/- 8)MUm in VEGF
      treated group and (170 +/- 23)MUm in VEGF and ADAMTS13 cotreated-group after 8
      hrs, respectively. The tube length is (450.6 +/- 16.6)% in VEGF-treated group and
      (235.3 +/- 19.0)% in VEGF and ADAMTS13 cotreated-group of that of control group
      after HUVECs cultured in matrigel for 16 hrs. The number of blood vessels
      decreased after treatment with ADAMTS13 in CAM assay. The number of blood vessels
      was (228.2 +/- 10.8)%, (69.2 +/- 21.1)%, (184.6 +/- 15.2)% in VEGF treated-group,
      ADAMTS13 treated-group and VEGF and ADAMTS13 cotreated-group of that of control
      group, respectively. Formation of capillary-like network in matrigel plugs
      containing VEGF was reduced to 43.5% by ADAMTS13 in matrigel plug assay in mouse
      model. CONCLUSION: ADAMTS13 inhibits the HUVECs proliferation, differentiation
      and migration in vitro. ADAMTS13 inhibits chick embryos vascularization and
      formation of capillary-like network in vivo.

PMID- 26304088
TI  - [Safety of 48 cases of infection after allogeneic stem cell transplantation
      treated with tigecycline].

PMID- 26304089
TI  - [Effect of arsenic trioxide on proliferation and apoptosis of human leukemia cell
      line MV4-11 cells].

PMID- 26304090
TI  - [The predictive value of Ki-67 expression for prognosis in patients with
      extranodal nasal type NK/T-cell lymphoma].

PMID- 26304091
TI  - [Diffuse large B cell lymphoma involving brachial plexus and vagus nerve: a case
      report].

PMID- 26304092
TI  - [The research progress of Von Willebrand disease].

PMID- 26304093
TI  - [Research advances on gene therapy for hemophilia A].

PMID- 26304094
TI  - [The research progress of costimulatory molecule B7 family in hematological
      malignancy].

PMID- 26304095
TI  - Clinical Pattern of Autism in Nigeria.
AB  - Autism, a global disorder has been widely studied in the Western world. However,
      there are limited studies on its occurrence, risk factors, and presentation in
      developing countries such as Nigeria. This retrospective study highlights the
      pattern of presentation of autism and presence of some risk factors in 75
      Nigerian cases referred to a private autism center. The diagnosis of autism was
      made using Diagnostic and Statistical Manual of Mental Disorders, 4th Edition
      (DSM IV), International Classification of Diseases Fourth edition, the Modified
      Checklist for Autism in Toddlers, Autism Treatment Evaluation Checklist, and
      Childhood Autism Rating Scale. There were 60 males and 15 females with a male to
      female ratio of 4:1. The mean age at presentation to the center was 6.87 +/- 4.20
      years and majority (91.9%) belonged to a high socioeconomic class. Already
      established risk factors, clinical features, and comorbidities of autism present
      among the study group were similar to findings in individuals with autism in
      other parts of the world.

PMID- 26304097
TI  - Infective endocarditis in the course of urosepsis E. coli ESBL(+) in a patient
      with Goodpasture's syndrome.

PMID- 26304098
TI  - Can continuous positive airway pressure therapy have antiarrhythmic properties?

PMID- 26304096
TI  - Resting state functional MRI reveals abnormal network connectivity in
      neurofibromatosis 1.
AB  - Neurofibromatosis type I (NF1) is a genetic disorder caused by mutations in the
      neurofibromin 1 gene at locus 17q11.2. Individuals with NF1 have an increased
      incidence of learning disabilities, attention deficits, and autism spectrum
      disorders. As a single-gene disorder, NF1 represents a valuable model for
      understanding gene-brain-behavior relationships. While mouse models have
      elucidated molecular and cellular mechanisms underlying learning deficits
      associated with this mutation, little is known about functional brain
      architecture in human subjects with NF1. To address this question, we used
      resting state functional connectivity magnetic resonance imaging (rs-fcMRI) to
      elucidate the intrinsic network structure of 30 NF1 participants compared with 30
      healthy demographically matched controls during an eyes-open rs-fcMRI scan. Novel
      statistical methods were employed to quantify differences in local connectivity
      (edge strength) and modularity structure, in combination with traditional global
      graph theory applications. Our findings suggest that individuals with NF1 have
      reduced anterior-posterior connectivity, weaker bilateral edges, and altered
      modularity clustering relative to healthy controls. Further, edge strength and
      modular clustering indices were correlated with IQ and internalizing symptoms.
      These findings suggest that Ras signaling disruption may lead to abnormal
      functional brain connectivity; further investigation into the functional
      consequences of these alterations in both humans and in animal models is
      warranted.

PMID- 26304099
TI  - Cost-effectiveness of Maintenance Treatment with a Barrier-strengthening
      Moisturizing Cream in Patients with Atopic Dermatitis in Finland, Norway and
      Sweden.
AB  - Atopic dermatitis is a chronic skin disorder with high prevalence, especially in
      the Nordic countries. Effective maintenance therapy during symptom-free episodes
      may prolong the time to eczema relapse according to a previously published
      clinical trial. The present study evaluates the cost-effectiveness of a barrier
      strengthening moisturizer containing 5% urea, compared with a moisturizer with no
      active ingredients during eczema-free periods. A health economic microsimulation
      model, based on efficacy data from the randomized clinical trial, analysed the
      cost-effectiveness of the barrier-strengthening treatment in Finland, Norway and
      Sweden. The barrier-strengthening moisturizer was cost-saving compared with the
      moisturizer with no active ingredients in all 3 countries. The result was
      confirmed in all but one sensitivity analysis. In conclusion, the barrier
      strengthening moisturizer is cost-effective as maintenance therapy for patients
      with atopic dermatitis compared with a moisturizer with no active ingredients. 

PMID- 26304100
TI  - Contribution of TIMP3 polymorphisms to the development of preeclampsia in Han
      Chinese women.
AB  - PURPOSE: The aim of this study was to investigate whether polymorphisms in the
      tissue inhibitor of metalloproteinase 3 gene (TIMP3) are associated with the risk
      of preeclampsia (PE) in Han Chinese women. METHODS: Nine single TIMP3 tag-single
      nucleotide polymorphisms were selected by Haploview and genotyped using the
      Sequenom method in 181 preeclamptic and 203 healthy pregnant women from eastern
      China. RESULTS: The allele frequencies of the tag-single nucleotide polymorphisms
      were not significantly different between groups (P > 0.05). However, the genotype
      distribution of rs135025 was shown to differ between the multigravidity PE
      subgroup (>3) and controls under additive (P = 0.018) and recessive models (P =
      0.008), while the genotype distribution of rs80272 differed significantly between
      the severe PE subgroup and controls under additive (P = 0.014) and dominant
      models (P = 0.041). Moreover, the H2 haplotype (A-C-G-T-A-A-G-C-G) was found to
      be associated with the risk of PE (P = 0.035). CONCLUSIONS: Genotypes of rs135025
      and rs80272 in TIMP3 may therefore influence susceptibility to PE, and pregnant
      women carrying the H2 haplotype might be more prone to developing PE.

PMID- 26304101
TI  - Early maternal serum beta-human chorionic gonadotropin (beta-hCG) levels and sex
      related growth difference of IVF embryos.
AB  - PURPOSE: Maternal serum beta-human chorionic gonadotropin (beta-hCG) represents
      the trophoblastic cell mass and is an indirect measurement of embryo development
      at early implantation stage. Studies in animals and human embryos detected sex
      related growth differences (SRGD) in favour of male embryos during the pre
      implantation period. The purpose of our study was to correlate SRGD and maternal
      serum beta-hCG at 16 days after embryo transfer. METHODS: We retrospectively
      analysed all (fresh and frozen) non-donor, single embryo transfers (SET),
      elective and not elective, that were performed between December 2008 and December
      2013. We included beta-hCG values from day 16 after oocyte collection of
      pregnancies resulting in live birth. Neonatal gender was retrieved from patient
      files. Male and female embryos were further grouped to cleavage and blastocyst
      stage transfers. Regression analysis for confounding variables included maternal
      age, maternal body mass index (BMI), use of micromanipulation (ICSI), embryo
      quality (grade), assisted hatching, day of transfer and fresh or frozen embryo
      transfer. RESULTS: Seven hundred eighty-six non-donor SETs resulted in live
      birth. After including only day 16 serum beta-hCG results, 525 SETs were
      analysed. Neonatal gender was available for 522 cases. Mean maternal serum beta
      hCG levels were similar, 347 +/- 191 IU/L in the male newborn group and 371 +/-
      200 IU/L in the female group. The difference between beta-hCG levels remained
      insignificant after adjusting for confounding variables. CONCLUSIONS: Early
      maternal beta-hCG levels after embryo transfers did not represent SRGD in our
      study.

PMID- 26304103
TI  - A comparison of hand-assisted laparoscopic surgery and conventional laparoscopic
      surgery in rectal cancer: a propensity score analysis.
AB  - PURPOSE: The aim of this study was to compare oncologic outcomes and
      perioperative variables following conventional laparoscopic surgery (LAP) versus
      hand-assisted laparoscopic surgery (HALS) for rectal cancer. METHODS: Between
      January 2008 and December 2012, 2680 consecutive patients who underwent curative
      resection for rectal cancer were analyzed. We used 1:1 propensity score matching
      to adjust for potential baseline confounders between groups including age, sex,
      body mass index, American Society of Anesthesiologists score, tumor distance from
      the anal verge, clinical T and N categories, pathologic T and N categories,
      preoperative carcinoembryonic antigen level, and the status of preoperative
      concurrent chemoradiotherapy. After matching, we analyzed 278 patients in each
      group (n = 556). RESULTS: The median follow-up period was 36.2 and 37.4 months in
      the HALS group and the conventional LAP group, respectively. Postoperative
      complications were not significantly different between the two groups (P =
      0.531). The 5-year overall survival rate was 88.8 % in the HALS group and 91.2 %
      in the conventional LAP group (P = 0.329). The 5-year disease-free survival rate
      was 77.0 % in the HALS group and 79.7 % in the conventional LAP group (P =
      0.591). CONCLUSIONS: HALS is considered a safe and feasible approach for rectal
      cancer treatment that enables the preservation of the advantages of conventional
      laparoscopic surgery.

PMID- 26304104
TI  - Multiplanar MDCT measurement of esophageal hiatus surface area: association with
      hiatal hernia and GERD.
AB  - BACKGROUND: Accurate measurement of esophageal hiatus size is clinically
      important, especially when antireflux surgery is planned. We present a novel
      method for in vivo measurement of esophageal hiatal surface area using MDCT
      multiplanar reconstruction. We aimed to determine whether large hiatal area is
      associated with hiatal hernia and gastroesophageal reflux disease. METHODS: We
      retrospectively analyzed subjects prospectively enrolled in the COPDGene((r))
      project. We created two test groups, one with hiatal hernia on chest CT and one
      with GERD on medical treatment identified by history without hernia. Matched
      control groups were formed. We performed CT postprocessing to define the double
      oblique plane of the esophageal hiatus, on which the hiatal surface area is
      manually traced. RESULTS: Subjects with hernia (n = 48) had larger mean hiatus
      areas than matched controls (6.9 vs. 2.5 cm(2), p < 0.0001), and were more likely
      to have GERD (42 vs. 10 %, p < 0.0005). Subjects with mixed (type III) hernias
      had larger hiatuses compared to subjects with sliding (type I) hernias, who, in
      turn, had larger hiatuses than subjects without hernia (p < 0.0001). Hernia
      negative subjects with GERD (n = 55) did not have significantly larger mean
      hiatal areas compared to matched controls (3.0 vs. 2.5 cm(2), p = 0.12). Twenty
      measurements obtained by two radiologists showed correlation of 0.93, with mean
      difference of 0.5 cm(2) (p = 0.20). CONCLUSIONS: We devised a method to measure
      in vivo esophageal hiatal surface area using MDCT reconstruction and established
      the normal size range for the first time. This methodology has the potential to
      guide decision-making in antireflux surgery technique preoperatively, and assess
      surgical result postoperatively. The presence of hernia correlated with large
      hiatuses and GERD. However, hiatal area failed to identify those with GERD in the
      absence of hiatal hernia.

PMID- 26304106
TI  - Laparoscopic colon resection: To prep or not to prep? Analysis of 1535 patients.
AB  - BACKGROUND: Mechanical bowel preparation (MBP) before elective open colon
      resection does not reduce the rate of postoperative anastomotic leakage. However,
      MBP is still routinely used in many countries, and there are very limited data
      regarding the utility of preoperative MBP in patients undergoing laparoscopic
      colon resection (LCR). The aim of this study was to challenge the use of MBP
      before elective LCR. METHODS: It is a retrospective analysis of a prospectively
      collected database. All patients undergoing elective LCR with primary anastomosis
      and no stoma were included. Preoperative MBP with polyethylene glycol solution
      was used routinely between April 1992 and December 2004, and then it was
      abandoned. The early postoperative outcomes in patients who had preoperative MBP
      (MBP group) and in patients who underwent LCR without preoperative MBP (No-MBP
      group) were compared. RESULTS: From April 1992 to December 2014, 1535 patients
      underwent LCR: 706 MBP patients and 829 No-MBP patients. There were no
      differences in demographic data, indication for surgery and type of procedure
      performed between MBP and No-MBP group patients. The incidence of anastomotic
      leakage was similar between the two groups (3.4 vs. 3.6 %, p = 0.925). No
      differences were observed in intra-abdominal abscesses (0.6 vs. 0.8 %, p =
      0.734), wound infections (0.6 vs. 1.4 %, p = 0.149), infectious extra-abdominal
      complications (1.8 vs. 3 %, p = 0.190), and non-infectious complications (6.1 vs.
      6.8 %, p = 0.672). The overall reoperation rate was 4.6 % for MBP patients and 5
      % for No-MBP patients (p = 0.813). CONCLUSION: The use of preoperative MBP does
      not seem to be associated with lower incidence of intra-abdominal septic
      complications after LCR.

PMID- 26304102
TI  - Transcriptional and epigenetic mechanisms of early cortical development: An
      examination of how Pax6 coordinates cortical development.
AB  - The development of the cortex is an elaborate process that integrates a plethora
      of finely tuned molecular processes ranging from carefully regulated gradients of
      transcription factors, dynamic changes in the chromatin landscape, or formation
      of protein complexes to elicit and regulate transcription. Combined with cellular
      processes such as cell type specification, proliferation, differentiation, and
      migration, all of these developmental processes result in the establishment of an
      adult mammalian cortex with its typical lamination and regional patterning. By
      examining in-depth the role of one transcription factor, Pax6, on the regulation
      of cortical development, its integration in the regulation of chromatin state,
      and its regulation by cis-regulatory elements, we aim to demonstrate the
      importance of integrating each level of regulation in our understanding of
      cortical development.

PMID- 26304105
TI  - Weight loss outcomes and complications from bariatric surgery in the super super
      obese.
AB  - BACKGROUND: Bariatric surgery has been established as the most effective long
      term treatment for morbid obesity. METHODS: We performed a retrospective review
      of SSO patients treated at our institute between 2008 and 2013 who underwent a
      laparoscopic gastric bypass (LGBP) or sleeve gastrectomy (LSG). The primary end
      point for this study was excess weight loss (EWL) at 1, 3, 6, and 12 months.
      Secondary end points included procedure length (PL), length of stay (LOS),
      diabetes management and postoperative complications. RESULTS: We identified 135
      SSO patients who underwent bariatric surgery (93 LGBP, 42 LSG) at our institute
      from 2008 to 2013 with a median follow-up of 49 months. The incidence of EWL > 30
      % for patients in the LGBP group was 3.9, 29.0, 72.2 and 94.6 % at 1, 3, 6 and 12
      months, respectively, while the incidence of EWL > 30 % in patients in the LSG
      group was 4.2, 25.0, 59.1 and 100 % at 1, 3, 6 and 12 months, respectively. PL
      was 124 +/- 49 min for the LGBP group and 98 + 51 min for the LSG group (p <
      0.005). LOS was on average 3.0 days (range 1-21) for the LGBP group and 3.4 days
      (range 1-13) for the LSG group (p = 0.41). Patients experienced a decrease in
      their hemoglobin A1C level by 10 % for the LGBP group and 9 % for the LSG group
      at 1 year (p = 0.89). Postoperative complications were seen in 15.1 % of LGBP
      patients and 4.8 % of LSG patients. CONCLUSIONS: Bariatric surgery is feasible in
      the SSO patients with comparable EWL outcomes and postoperative complications to
      historical non-SSO patients.

PMID- 26304107
TI  - Current state of virtual reality simulation in robotic surgery training: a
      review.
AB  - BACKGROUND: Worldwide, the annual number of robotic surgical procedures continues
      to increase. Robotic surgical skills are unique from those used in either open or
      laparoscopic surgery. The acquisition of a basic robotic surgical skill set may
      be best accomplished in the simulation laboratory. We sought to review the
      current literature pertaining to the use of virtual reality (VR) simulation in
      the acquisition of robotic surgical skills on the da Vinci Surgical System.
      MATERIALS AND METHODS: A PubMed search was conducted between December 2014 and
      January 2015 utilizing the following keywords: virtual reality, robotic surgery,
      da Vinci, da Vinci skills simulator, SimSurgery Educational Platform, Mimic dV
      Trainer, and Robotic Surgery Simulator. Articles were included if they were
      published between 2007 and 2015, utilized VR simulation for the da Vinci Surgical
      System, and utilized a commercially available VR platform. RESULTS: The initial
      search criteria returned 227 published articles. After all inclusion and
      exclusion criteria were applied, a total of 47 peer-reviewed manuscripts were
      included in the final review. CONCLUSIONS: There are many benefits to utilizing
      VR simulation for robotic skills acquisition. Four commercially available
      simulators have been demonstrated to be capable of assessing robotic skill. Three
      of the four simulators demonstrate the ability of a VR training curriculum to
      improve basic robotic skills, with proficiency-based training being the most
      effective training style. The skills obtained on a VR training curriculum are
      comparable with those obtained on dry laboratory simulation. The future of VR
      simulation includes utilization in assessment for re-credentialing purposes,
      advanced procedural-based training, and as a warm-up tool prior to surgery.

PMID- 26304108
TI  - Design, synthesis and molecular docking of salicylic acid derivatives containing
      metronidazole as a new class of antimicrobial agents.
AB  - A series of novel salicylic acid derivatives containing metronidazole as
      Staphylococcus aureus Tyrosyl-tRNA synthetase (TyrRS) inhibitors have been
      synthesized and evaluated their biology activities as potential antibacterial
      agents. Among these compounds, compound 5r exhibited the most potent
      antibacterial activity against Gram-positive (S. aureus ATCC 6538 and Bacillus
      subtilis ATCC 6633) and Gram-negative (Escherichia coli ATCC 35218 and
      Pseudomonas aeruginosa ATCC 13525) with MICs of 0.39-1.57 MUg/mL and showed the
      most potent S. aureus Tyrosyl-tRNA synthetase inhibitory with 2.3 MUM. Docking
      simulation was performed to insert compound 5r into the crystal structure of S.
      aureus Tyrosyl-tRNA synthetase active site to determine the probable binding
      model. These results suggested that compound 5r may be a promising antibacterial
      agent.

PMID- 26304109
TI  - 'We see it as being heterosexualised, being put into a care home': gender,
      sexuality and housing/care preferences among older LGB individuals in the UK.
AB  - This paper considers the lack of choice in sheltered housing and
      residential/nursing care provision for older lesbian, gay and bisexual (LGB)
      individuals in the UK. While there is a growing body of knowledge about their
      concerns about current options, the precise kinds of alternative provision which
      older LGB individuals would prefer are not yet well understood. This article
      reports on a qualitative study conducted in 2012 which aimed to explore ageing,
      gender and sexuality from an equalities perspective. The study deployed semi
      structured interviews with 60 older LGB individuals living in the UK, and used a
      thematic analysis approach to the data. This paper describes one aspect of the
      data, relating to participants' concerns about health and social care provision.
      The analysis identified several key themes underpinning older LGB individuals'
      concerns about mainstream sheltered accommodation and residential care, namely:
      lack of visibility, risky visibility, unequal openness and compulsory co
      occupation of care spaces. It highlights the significance of gender for
      housing/care preferences, with a greater proportion of older LGB women wanting
      gender- and/or sexuality-specific provision compared with men. The social policy,
      equality and human rights implications of these findings are considered.

PMID- 26304110
TI  - Double seal technique to obliterate the eustachian tube orifice: a novel method
      for the treatment of recalcitrant cerebrospinal fluid leak.
AB  - OBJECTIVE: To demonstrate a novel and effective surgical technique for the
      treatment of refractory cerebrospinal fluid rhinorrhoea after skull base surgery.
      The novel surgical technique is described and the findings of a review of
      relevant world English-language publications are reported. CASE REPORT: A 44-year
      old woman, otherwise fit and well, presented with more than a 2-year history of
      right-sided facial pain. A diagnosis of classical trigeminal neuralgia was made.
      Surgical treatment was undertaken with a retromastoid suboccipital craniotomy.
      Post-operatively, the patient showed signs of right-sided cerebrospinal fluid
      rhinorrhoea which was recalcitrant. In light of a continuous leak and several
      hospital admissions, a novel technique was performed whereby the eustachian tube
      orifice was obliterated using an endonasal endoscopic approach. The technique
      proved to be successful, with no further leakage. CONCLUSION: Endoscopic
      obliteration of the eustachian tube using a double seal technique is a simple,
      safe and effective procedure in the treatment of a refractory cerebrospinal fluid
      leak.

PMID- 26304111
TI  - Thoracoscopic Surgery for Partial Anomalous Pulmonary Venous Connection with Dual
      Drainage.
AB  - We report our technique for thoracoscopic surgery for a 15-year-old female (body
      weight, 59 kg) diagnosed with partial anomalous pulmonary venous connection with
      dual drainage. A large anomalous right lower pulmonary vein (RLPV) was drained
      into the inferior vena cava and left atrium, along with thoracoscopic ligation
      and clipping of RLPV and some anomalous hepatic veins.

PMID- 26304113
TI  - Myostatin dysfunction is associated with reduction in overload induced
      hypertrophy of soleus muscle in mice.
AB  - The aim of the study was to investigate if myostatin dysfunction would promote
      the gain in muscle mass and peak isometric force (P0 ) of soleus muscle (SOL) in
      response to functional overloading (FO) after ablation of the gastrocnemius
      muscle. Fifteen male Berlin high (BEH) mice homozygous for the compact mutation
      causing dysfunction of myostatin and 17 mice with the corresponding wild-type
      allele (BEH+/+) were subjected to FO of SOL for 28 days at the age of 14 weeks.
      Compared with BEH+/+ mice, SOL of BEH was heavier (mean +/- SD, 13.5 +/- 1.5 vs
      21.4 +/- 1.8 mg, respectively, P < 0.001). After FO, SOL mass increased
      relatively more in BEH+/+ than BEH strain (34.9 +/- 11.5 vs 17.7 +/- 11.9%,
      respectively, P < 0.01). P0 fell (P < 0.01) only in BEH strain, which also showed
      an increase (P < 0.01) in optimal muscle length. Specific P0 became even more
      depressed in BEH compared with BEH+/+ strain (8.4 +/- 1.4 vs 10.8 +/- 1.3 N/g,
      respectively, P < 0.001). Phosphorylation p70 S6 kinase did not differ between
      the strains. In summary, myostatin dysfunction impairs adaptation of SOL muscle
      to high functional demands. 

PMID- 26304114
TI  - Structural Analysis of a Family 101 Glycoside Hydrolase in Complex with
      Carbohydrates Reveals Insights into Its Mechanism.
AB  - O-Linked glycosylation is one of the most abundant post-translational
      modifications of proteins. Within the secretory pathway of higher eukaryotes, the
      core of these glycans is frequently an N-acetylgalactosamine residue that is
      alpha-linked to serine or threonine residues. Glycoside hydrolases in family 101
      are presently the only known enzymes to be able to hydrolyze this glycosidic
      linkage. Here we determine the high-resolution structures of the catalytic domain
      comprising a fragment of GH101 from Streptococcus pneumoniae TIGR4, SpGH101, in
      the absence of carbohydrate, and in complex with reaction products, inhibitor,
      and substrate analogues. Upon substrate binding, a tryptophan lid (residues 724
      WNW-726) closes on the substrate. The closing of this lid fully engages the
      substrate in the active site with Asp-764 positioned directly beneath C1 of the
      sugar residue bound within the -1 subsite, consistent with its proposed role as
      the catalytic nucleophile. In all of the bound forms of the enzyme, however, the
      proposed catalytic acid/base residue was found to be too distant from the
      glycosidic oxygen (>4.3 A) to serve directly as a general catalytic acid/base
      residue and thereby facilitate cleavage of the glycosidic bond. These same
      complexes, however, revealed a structurally conserved water molecule positioned
      between the catalytic acid/base and the glycosidic oxygen. On the basis of these
      structural observations we propose a new variation of the retaining glycoside
      hydrolase mechanism wherein the intervening water molecule enables a Grotthuss
      proton shuttle between Glu-796 and the glycosidic oxygen, permitting this residue
      to serve as the general acid/base catalytic residue. 

PMID- 26304112
TI  - Fibroblast activation protein-alpha, a stromal cell surface protease, shapes key
      features of cancer associated fibroblasts through proteome and degradome
      alterations.
AB  - Cancer associated fibroblasts (CAFs) constitute an abundant stromal component of
      most solid tumors. Fibroblast activation protein (FAP) alpha is a cell surface
      protease that is expressed by CAFs. We corroborate this expression profile by
      immunohistochemical analysis of colorectal cancer specimens. To better understand
      the tumor-contextual role of FAPalpha, we investigate how FAPalpha shapes
      functional and proteomic features of CAFs using loss- and gain-of function
      cellular model systems. FAPalpha activity has a strong impact on the secreted CAF
      proteome ("secretome"), including reduced levels of anti-angiogenic factors,
      elevated levels of transforming growth factor (TGF) beta, and an impact on matrix
      processing enzymes. Functionally, FAPalpha mildly induces sprout formation by
      human umbilical vein endothelial cells. Moreover, loss of FAPalpha leads to a
      more epithelial cellular phenotype and this effect was rescued by exogenous
      application of TGFbeta. In collagen contraction assays, FAPalpha induced a more
      contractile cellular phenotype. To characterize the proteolytic profile of
      FAPalpha, we investigated its specificity with proteome-derived peptide libraries
      and corroborated its preference for cleavage carboxy-terminal to proline
      residues. By "terminal amine labeling of substrates" (TAILS) we explored FAPalpha
      dependent cleavage events. Although FAPalpha acts predominantly as an amino
      dipeptidase, putative FAPalpha cleavage sites in collagens are present throughout
      the entire protein length. In contrast, putative FAPalpha cleavage sites in non
      collagenous proteins cluster at the amino-terminus. The degradomic study
      highlights cell-contextual proteolysis by FAPalpha with distinct positional
      profiles. Generally, our findings link FAPalpha to key aspects of CAF biology and
      attribute an important role in tumor-stroma interaction to FAPalpha. 

PMID- 26304115
TI  - The Alternative Splicing of Cytoplasmic Polyadenylation Element Binding Protein 2
      Drives Anoikis Resistance and the Metastasis of Triple Negative Breast Cancer.
AB  - Triple negative breast cancer (TNBC) represents an anomalous subset of breast
      cancer with a greatly reduced (30%) 5-year survival rate. The enhanced mortality
      and morbidity of TNBC arises from the high metastatic rate, which requires the
      acquisition of AnR, a process whereby anchorage-dependent cells become resistant
      to cell death induced by detachment. In this study TNBC cell lines were selected
      for AnR, and these cell lines demonstrated dramatic enhancement in the formation
      of lung metastases as compared with parental cells. Genetic analysis of the AnR
      subclones versus parental cells via next generation sequencing and analysis of
      global alternative RNA splicing identified that the mRNA splicing of cytoplasmic
      polyadenylation element binding 2 (CPEB2), a translational regulator, was altered
      in AnR TNBC cells. Specifically, increased inclusion of exon 4 into the mature
      mRNA to produce the CPEB2B isoform was observed in AnR cell lines. Molecular
      manipulations of CPEB2 splice variants demonstrated a key role for this RNA
      splicing event in the resistance of cells to anoikis. Specifically, down
      regulation of the CPEB2B isoform using siRNA re-sensitized the AnR cell lines to
      detachment-induced cell death. The ectopic expression of CPEB2B in parental TNBC
      cell lines induced AnR and dramatically increased metastatic potential.
      Importantly, alterations in the alternative splicing of CPEB2 were also observed
      in human TNBC and additional subtypes of human breast cancer tumors linked to a
      high metastatic rate. Our findings demonstrate that the regulation of CPEB2 mRNA
      splicing is a key mechanism in AnR and a driving force in TNBC metastasis. 

PMID- 26304116
TI  - Small Retinoprotective Peptides Reveal a Receptor-binding Region on Pigment
      Epithelium-derived Factor.
AB  - The cytoprotective effects of pigment epithelium-derived factor (PEDF) require
      interactions between an as of a yet undefined region with a distinct ectodomain
      on the PEDF receptor (PEDF-R). Here we characterized the area in PEDF that
      interacts with PEDF-R to promote photoreceptor survival. Molecular docking
      studies suggested that the ligand binding site of PEDF-R interacts with the
      neurotrophic region of PEDF (44-mer, positions 78-121). Binding assays
      demonstrated that PEDF-R bound the 44-mer peptide. Moreover, peptide P1 from the
      PEDF-R ectodomain had affinity for the 44-mer and a shorter fragment within it,
      17-mer (positions 98-114). Single residue substitutions to alanine along the 17
      mer sequence were designed and tested for binding and biological activity.
      Altered 17-mer[R99A] did not bind to the P1 peptide, whereas 17-mer[H105A] had
      higher affinity than the unmodified 17-mer. Peptides 17-mer, 17-mer[H105A], and
      44-mer exhibited cytoprotective effects in cultured retina R28 cells.
      Intravitreal injections of these peptides and PEDF in the rd1 mouse model of
      retinal degeneration decreased the numbers of dying photoreceptors, 17-mer[H105A]
      being most effective. The blocking peptide P1 hindered their protective effects
      both in retina cells and in vivo. Thus, in addition to demonstrating that the
      region composed of positions 98-114 of PEDF contains critical residues for PEDF-R
      interaction that mediates survival effects, the findings reveal distinct small
      PEDF fragments with neurotrophic effects on photoreceptors. 

PMID- 26304117
TI  - Molecular Characterization of Caveolin-induced Membrane Curvature.
AB  - The generation of caveolae involves insertion of the cholesterol-binding integral
      membrane protein caveolin-1 (Cav1) into the membrane, however, the precise
      molecular mechanisms are as yet unknown. We have speculated that insertion of the
      caveolin scaffolding domain (CSD), a conserved amphipathic region implicated in
      interactions with signaling proteins, is crucial for caveola formation. We now
      define the core membrane-juxtaposed region of Cav1 and show that the
      oligomerization domain and CSD are protected by tight association with the
      membrane in both mature mammalian caveolae and a model prokaryotic system for
      caveola biogenesis. Cryoelectron tomography reveals the core membrane-juxtaposed
      domain to be sufficient to maintain oligomerization as defined by polyhedral
      distortion of the caveolar membrane. Through mutagenesis we demonstrate the
      importance of the membrane association of the oligomerization domain/CSD for
      defined caveola biogenesis and furthermore, highlight the functional significance
      of the intramembrane domain and the CSD for defined caveolin-induced membrane
      deformation. Finally, we define the core structural domain of Cav1, constituting
      only 66 amino acids and of great potential to nanoengineering applications, which
      is required for caveolin-induced vesicle formation in a bacterial system. These
      results have significant implications for understanding the role of Cav1 in
      caveola formation and in regulating cellular signaling events.

PMID- 26304118
TI  - Receptor Level Mechanisms Are Required for Epidermal Growth Factor (EGF)
      stimulated Extracellular Signal-regulated Kinase (ERK) Activity Pulses.
AB  - In both physiological and cell culture systems, EGF-stimulated ERK activity
      occurs in discrete pulses within individual cells. Many feedback loops are
      present in the EGF receptor (EGFR)-ERK network, but the mechanisms driving
      pulsatile ERK kinetics are unknown. Here, we find that in cells that respond to
      EGF with frequency-modulated pulsatile ERK activity, stimulation through a
      heterologous TrkA receptor system results in non-pulsatile, amplitude-modulated
      activation of ERK. We further dissect the kinetics of pulse activity using a
      combination of FRET- and translocation-based reporters and find that EGFR
      activity is required to maintain ERK activity throughout the 10-20-minute
      lifetime of pulses. Together, these data indicate that feedbacks operating within
      the core Ras-Raf-MEK-ERK cascade are insufficient to drive discrete pulses of ERK
      activity and instead implicate mechanisms acting at the level of EGFR.

PMID- 26304119
TI  - MYCBP2 Is a Guanosine Exchange Factor for Ran Protein and Determines Its
      Localization in Neurons of Dorsal Root Ganglia.
AB  - The small GTPase Ran coordinates retrograde axonal transport in neurons, spindle
      assembly during mitosis, and the nucleo-cytoplasmic transport of mRNA. Its
      localization is tightly regulated by the GTPase-activating protein RanGAP1 and
      the nuclear guanosine exchange factor (GEF) RCC1. We show that loss of the
      neuronal E3 ubiquitin ligase MYCBP2 caused the up-regulation of Ran and RanGAP1
      in dorsal root ganglia (DRG) under basal conditions and during inflammatory
      hyperalgesia. SUMOylated RanGAP1 physically interacted with MYCBP2 and inhibited
      its E3 ubiquitin ligase activity. Stimulation of neurons induced a RanGAP1
      dependent translocation of MYCBP2 to the nucleus. In the nucleus of DRG neurons
      MYCBP2 co-localized with Ran and facilitated through its RCC1-like domain the
      GDP/GTP exchange of Ran. In accordance with the necessity of a GEF to promote GTP
      binding and nuclear export of Ran, the nuclear localization of Ran was strongly
      increased in MYCBP2-deficient DRGs. The finding that other GEFs for Ran besides
      RCC1 exist gives new insights in the complexity of the regulation of the Ran
      signaling pathway. 

PMID- 26304120
TI  - Loss of a Functionally and Structurally Distinct ld-Transpeptidase, LdtMt5,
      Compromises Cell Wall Integrity in Mycobacterium tuberculosis.
AB  - The final step of peptidoglycan (PG) biosynthesis in bacteria involves cross
      linking of peptide side chains. This step in Mycobacterium tuberculosis is
      catalyzed by ld- and dd-transpeptidases that generate 3->3 and 4->3 transpeptide
      linkages, respectively. M. tuberculosis PG is predominantly 3->3 cross-linked,
      and LdtMt2 is the dominant ld-transpeptidase. There are four additional sequence
      paralogs of LdtMt2 encoded by the genome of this pathogen, and the reason for
      this apparent redundancy is unknown. Here, we studied one of the paralogs,
      LdtMt5, and found it to be structurally and functionally distinct. The structures
      of apo-LdtMt5 and its meropenem adduct presented here demonstrate that, despite
      overall architectural similarity to LdtMt2, the LdtMt5 active site has marked
      differences. The presence of a structurally divergent catalytic site and a
      proline-rich C-terminal subdomain suggest that this protein may have a distinct
      role in PG metabolism, perhaps involving other cell wall-anchored proteins.
      Furthermore, M. tuberculosis lacking a functional copy of LdtMt5 displayed
      aberrant growth and was more susceptible to killing by crystal violet, osmotic
      shock, and select carbapenem antibiotics. Therefore, we conclude that LdtMt5 is
      not a functionally redundant ld-transpeptidase, but rather it serves a unique and
      important role in maintaining the integrity of the M. tuberculosis cell wall. 

PMID- 26304121
TI  - Postnatal Deletion of Fat Storage-inducing Transmembrane Protein 2 (FIT2/FITM2)
      Causes Lethal Enteropathy.
AB  - Lipid droplets (LDs) are phylogenetically conserved cytoplasmic organelles that
      store neutral lipids within a phospholipid monolayer. LDs compartmentalize lipids
      and may help to prevent cellular damage caused by their excess or bioactive
      forms. FIT2 is a ubiquitously expressed transmembrane endoplasmic reticulum (ER)
      membrane protein that has previously been implicated in LD formation in mammalian
      cells and tissue. Recent data indicate that FIT2 plays an essential role in fat
      storage in an in vivo constitutive adipose FIT2 knock-out mouse model, but the
      physiological effects of postnatal whole body FIT2 depletion have never been
      studied. Here, we show that tamoxifen-induced FIT2 deletion using a whole body
      ROSA26CreER(T2)-driven FIT2 knock-out (iF2KO) mouse model leads to lethal
      intestinal pathology, including villus blunting and death of intestinal crypts,
      and loss of lipid absorption. iF2KO mice lose weight and die within 2 weeks after
      the first tamoxifen dose. At the cellular level, LDs failed to form in iF2KO
      enterocytes after acute oil challenge and instead accumulated within the ER.
      Intestinal bile acid transporters were transcriptionally dysregulated in iF2KO
      mice, leading to the buildup of bile acids within enterocytes. These data support
      the conclusion that FIT2 plays an essential role in regulating intestinal health
      and survival postnatally. 

PMID- 26304122
TI  - Crystal structure of PnpCD, a two-subunit hydroquinone 1,2-dioxygenase, reveals a
      novel structural class of Fe2+-dependent dioxygenases.
AB  - Aerobic microorganisms have evolved a variety of pathways to degrade aromatic and
      heterocyclic compounds. However, only several classes of oxygenolytic fission
      reaction have been identified for the critical ring cleavage dioxygenases. Among
      them, the most well studied dioxygenases proceed via catecholic intermediates,
      followed by noncatecholic hydroxy-substituted aromatic carboxylic acids.
      Therefore, the recently reported hydroquinone 1,2-dioxygenases add to the
      diversity of ring cleavage reactions. Two-subunit hydroquinone 1,2-dioxygenase
      PnpCD, the key enzyme in the hydroquinone pathway of para-nitrophenol
      degradation, catalyzes the ring cleavage of hydroquinone to gamma-hydroxymuconic
      semialdehyde. Here, we report three PnpCD structures, named apo-PnpCD, PnpCD
      Fe(3+), and PnpCD-Cd(2+)-HBN (substrate analog hydroxyenzonitrile), respectively.
      Structural analysis showed that both the PnpC and the C-terminal domains of PnpD
      comprise a conserved cupin fold, whereas PnpC cannot form a competent metal
      binding pocket as can PnpD cupin. Four residues of PnpD (His-256, Asn-258, Glu
      262, and His-303) were observed to coordinate the iron ion. The Asn-258
      coordination is particularly interesting because this coordinating residue has
      never been observed in the homologous cupin structures of PnpCD. Asn-258 is
      proposed to play a pivotal role in binding the iron prior to the enzymatic
      reaction, but it might lose coordination to the iron when the reaction begins.
      PnpD also consists of an intriguing N-terminal domain that might have functions
      other than nucleic acid binding in its structural homologs. In summary, PnpCD has
      no apparent evolutionary relationship with other iron-dependent dioxygenases and
      therefore defines a new structural class. The study of PnpCD might add to the
      understanding of the ring cleavage of dioxygenases. 

PMID- 26304123
TI  - mRNA Targeting to Endoplasmic Reticulum Precedes Ago Protein Interaction and
      MicroRNA (miRNA)-mediated Translation Repression in Mammalian Cells.
AB  - MicroRNA (miRNA) binds to the 3'-UTR of its target mRNAs to repress protein
      synthesis. Extensive research was done to understand the mechanism of miRNA
      mediated repression in animal cells. Considering the progress in understanding
      the mechanism, information about the subcellular sites of miRNA-mediated
      repression is surprisingly limited. In this study, using an inducible expression
      system for an miRNA target message, we have delineated how a target mRNA passes
      through polysome association and Ago2 interaction steps on rough endoplasmic
      reticulum (ER) before the miRNA-mediated repression sets in. From this study, de
      novo formed target mRNA localization to the ER-bound polysomes manifested as the
      earliest event, which is followed by Ago2 micro-ribonucleoprotein binding, and
      translation repression of target message. Compartmentalization of this process to
      rough ER membrane ensures enrichment of miRNA-targeted messages and micro
      ribonucleoprotein components on ER upon reaching a steady state. 

PMID- 26304124
TI  - Saturated fatty acids induce post-transcriptional regulation of HAMP mRNA via AU
      rich element-binding protein, human antigen R (HuR).
AB  - Iron is implicated in fatty liver disease pathogenesis. The human hepcidin gene,
      HAMP, is the master switch of iron metabolism. The aim of this study is to
      investigate the regulation of HAMP expression by fatty acids in HepG2 cells. For
      these studies, both saturated fatty acids (palmitic acid (PA) and stearic acid
      (SA)) and unsaturated fatty acid (oleic acid (OA)) were used. PA and, to a lesser
      extent, SA, but not OA, up-regulated HAMP mRNA levels, as determined by real-time
      PCR. To understand whether PA regulates HAMP mRNA at the transcriptional or post
      transcriptional level, the transcription inhibitor actinomycin D was employed. PA
      mediated induction of HAMP mRNA expression was not blocked by actinomycin D.
      Furthermore, PA activated HAMP 3'-UTR, but not promoter, activity, as shown by
      reporter assays. HAMP 3'-UTR harbors a single AU-rich element (ARE). Mutation of
      this ARE abolished the effect of PA, suggesting the involvement of ARE-binding
      proteins. The ARE-binding protein human antigen R (HuR) stabilizes mRNA through
      direct interaction with AREs on 3'-UTR. HuR is regulated by phosphorylation
      mediated nucleo-cytoplasmic shuttling. PA activated this process. The binding of
      HuR to HAMP mRNA was also induced by PA in HepG2 cells. Silencing of HuR by siRNA
      abolished PA-mediated up-regulation of HAMP mRNA levels. PKC is known to
      phosphorylate HuR. Staurosporine, a broad-spectrum PKC inhibitor, inhibited both
      PA-mediated translocation of HuR and induction of HAMP expression. Similarly,
      rottlerin, a novel class PKC inhibitor, abrogated PA-mediated up-regulation of
      HAMP expression. In conclusion, lipids mediate post-transcriptional regulation of
      HAMP throughPKC- and HuR-dependent mechanisms. 

PMID- 26304126
TI  - Microdissection TESE is superior to conventional TESE in patients with
      nonobstructive azoospermia caused by Y chromosome microdeletions.
AB  - Nonobstructive azoospermia is caused in up to 10% by microdeletions of the Y
      chromosome in the azoospermia factor (AZF) region, which is divided into three
      nonoverlapping areas (AZFa, AZFb and AZFc). In 25 male patients with AZF
      microdeletions, the results of two different techniques for surgical sperm
      retrieval (SR), conventional multilocular TESE and microdissection TESE, were
      studied retrospectively over a period of 19 years. Conventional multilocular TESE
      was carried out in 11 patients and microdissection TESE in 14 patients.
      Successful SR was possible only in patients with isolated AZFc microdeletions, so
      only the 20 patients with AZFc microdeletions alone were taken into account for
      the comparison of the both operative techniques. The sperm detection rate for
      conventional multilocular TESE was 25%, the sperm detection for microdissection
      TESE was significantly higher with 67%. In all patients, a histological
      examination of the testicular tissue was carried out, which showed a mixed
      picture, but Sertoli-cell-only syndrome in most cases. FSH was no prognostic
      marker for successful SR. In two of six couples performing an intracytoplasmic
      sperm injection until now, a pregnancy occurred. 

PMID- 26304127
TI  - Characterization and Differentiation of Stem Cells Isolated from Human Newborn
      Foreskin Tissue.
AB  - Circumcision is described as a cultural, medical, and religious process which
      states surgical removal of the foreskin either partly or fully. Cells isolated
      from the circumcised tissues are referred as foreskin cells. They have been
      thought as feeder cell lines for embryonic stem cells. Their fibroblastic
      properties were also utilized for several experiments. The waste tissues that
      remain after the circumcision thought to have stem cell properties. Therefore,
      there have been very few attempts to expose their stem cell properties without
      turning them into induced pluripotent stem cells. Although stem cell isolation
      from prepuce and their mesenchymal multilineage differentiation potential have
      been presented many times in the literature, the current study explored
      hematopoietical phenotype of newborn foreskin stem cells for the first time.
      According to the results, human newborn foreskin stem cells (hnFSSCs) were
      identified by their capability to turn into all three germ layer cell types under
      in vitro conditions. In addition, these cells have exhibited a stable phenotype
      and have remained as a monolayer in vitro. hnFSSCs suggested to carry different
      treatment potentials for bone damages, cartilage problems, nerve damages, lesion
      formations, and other diseases that are derive from mesodermal, endodermal, and
      ectodermal origins. Owing to the location of the tissue in the body and
      differentiation capabilities of hnFSSCs, these cells can be considered as easily
      obtainable and utilizable even better than the other stem cell sources. In
      addition, hnFSSCs offers a great potential for tissue engineering approaches due
      to exhibiting embryonic stem cell-like characteristics, not having any ethical
      issues, and teratoma induction as in embryonic stem cell applications. 

PMID- 26304125
TI  - Differential Editosome Protein Function between Life Cycle Stages of Trypanosoma
      brucei.
AB  - Uridine insertion and deletion RNA editing generates functional mitochondrial
      mRNAs in Trypanosoma brucei. The mRNAs are differentially edited in bloodstream
      form (BF) and procyclic form (PF) life cycle stages, and this correlates with the
      differential utilization of glycolysis and oxidative phosphorylation between the
      stages. The mechanism that controls this differential editing is unknown. Editing
      is catalyzed by multiprotein ~20S editosomes that contain endonuclease, 3'
      terminal uridylyltransferase, exonuclease, and ligase activities. These
      editosomes also contain KREPB5 and KREPA3 proteins, which have no functional
      catalytic motifs, but they are essential for parasite viability, editing, and
      editosome integrity in BF cells. We show here that repression of KREPB5 or KREPA3
      is also lethal in PF, but the effects on editosome structure differ from those in
      BF. In addition, we found that point mutations in KREPB5 or KREPA3 differentially
      affect cell growth, editosome integrity, and RNA editing between BF and PF
      stages. These results indicate that the functions of KREPB5 and KREPA3 editosome
      proteins are adjusted between the life cycle stages. This implies that these
      proteins are involved in the processes that control differential editing and that
      the 20S editosomes differ between the life cycle stages.

PMID- 26304128
TI  - Batch and Pulsed Fed-Batch Cultures of Aspergillus flavipes FP-500 Growing on
      Lemon Peel at Stirred Tank Reactor.
AB  - Aspergillus flavipes FP-500 grew up on submerged cultures using lemon peel as the
      only carbon source, developing several batch and pulsed fed-batch trials on a
      stirred tank reactor. The effect of carbon source concentration, reducing sugar
      presence and initial pH on exopectinase and endopectinase production, was
      analyzed on batch cultures. From this, we observed that the highest substrate
      concentration favored biomass (X max) but had not influence on the corresponding
      specific production (q p) of both pectinases; the most acid condition provoked
      higher endopectinase-specific productions but had not a significant effect on
      those corresponding to exopectinases; and reducing sugar concentrations higher
      than 1.5 g/L retarded pectinase production. On the other hand, by employing the
      pulsed fed-batch operation mode, we observed a prolonged growth phase, and an
      increase of about twofold on endopectinase production without a significant raise
      on biomass concentration. So, pulsed fed-batch seems to be a good alternative for
      obtaining higher endopectinase titers by using high lemon peel quantities without
      having mixing and repression problems to the system. The usefulness of
      unstructured kinetic models for explaining, under a theoretic level, the behavior
      of the fungus along the batch culture with regard to pectinase production was
      evident. 

PMID- 26304129
TI  - Purification and Characterization of a Lectin from Green Split Peas (Pisum
      sativum).
AB  - Lectins have captured the attention of a large number of researchers on account
      of their various exploitable activities, including antitumor, immunomodulatory,
      antifungal, as well as HIV reverse transcriptase inhibitory activities. A
      mannose/glucose-specific lectin was isolated from green split peas (a variety of
      Pisum sativum) and characterized. The purification step involved anion-exchange
      chromatography on a DEAE-cellulose column, cation-exchange chromatography on an
      SP-Sepharose column, and gel filtration by fast protein liquid chromatography
      (FPLC) on Superdex 200. The purified lectin had a native molecular mass of around
      50 kDa as determined by size exclusion chromatography. It appeared as a
      heterotetramer, composed of two distinct polypeptide bands with a molecular mass
      of 6 and 19 kDa, respectively, in sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE). The N-terminal sequence of green split pea lectin
      shows some degree of homology compared to lectins from other legume species. Its
      hemagglutinating activity was inhibited by glucose, mannose, and sucrose, and
      attenuated at pH values higher than 12 or lower than 3. Hemagglutinating activity
      was preserved at temperatures lower than 80  degrees C. The lectin did not show
      antifungal activity toward fungi including Fusarium oxysporum, Botrytis cinerea,
      and Mycosphaerella arachidicola. Green split pea lectin showed a mitogenic effect
      toward murine splenocytes and could inhibit the activity of HIV-1 reverse
      transcriptase. 

PMID- 26304130
TI  - Substituted judgment, procreative beneficence, and the Ashley treatment.

PMID- 26304132
TI  - Distinct Temporal Regulation of RET Isoform Internalization: Roles of Clathrin
      and AP2.
AB  - The RET receptor tyrosine kinase (RTK) contributes to kidney and nervous system
      development, and is implicated in a number of human cancers. RET is expressed as
      two protein isoforms, RET9 and RET51, with distinct interactions and signaling
      properties that contribute to these processes. RET isoforms are internalized from
      the cell surface into endosomal compartments in response to glial cell line
      derived neurotropic factor (GDNF) ligand stimulation but the specific mechanisms
      of RET trafficking remain to be elucidated. Here, we used total internal
      reflection fluorescence (TIRF) microscopy to demonstrate that RET internalization
      occurs primarily through clathrin coated pits (CCPs). Activated RET receptors
      colocalize with clathrin, but not caveolin. The RET51 isoform is rapidly and
      robustly recruited to CCPs upon GDNF stimulation, while RET9 recruitment occurs
      more slowly and is less pronounced. We showed that the clathrin-associated
      adaptor protein complex 2 (AP2) interacts directly with each RET isoform through
      its AP2 MU subunit, and is important for RET internalization. Our data establish
      that interactions with the AP2 complex promote RET receptor internalization via
      clathrin-mediated endocytosis but that RET9 and RET51 have distinct
      internalization kinetics that may contribute to differences in their biological
      functions. 

PMID- 26304134
TI  - Influence of phosphorus management on melon (Cucumis melo L.) fruit quality.
AB  - BACKGROUND: At harvest time, melon quality is related to internal and external
      parameters, which are very important for consumer attractiveness and marketable
      yield. Several agronomic factors can affect the quality of melon fruits and among
      them mineral availability may play a significant role. Therefore the aim of the
      work was to investigate the effect of phosphorus fertigation on melon fruit
      (Cucumis melo L.) qualitative characteristics, such as fruit size and yield, pulp
      colour and firmness, aroma and taste, as well as the accumulation of bioactive
      antioxidant compounds, namely phenols and carotenoids, and their antiradical
      properties. RESULTS: Results allowed us to extrapolate the optimal P doses to be
      used for melon fertigation, to achieve high yield and fruit quality
      characteristics. Modelling the optimal P dose allowed us to maximize yield and
      resulted in around 257 kg P2 O5 ha(-1) , even if the quality indices relating to
      carotenoid content, texture and colour of the melon flesh were not significantly
      different between samples fertigated with the two highest levels tested.
      CONCLUSION: It can be assumed that the level of 200 kg P2 O5 ha(-1) would be a
      good compromise between optimization of agronomic performance and melon fruit
      quality. (c) 2015 Society of Chemical Industry.

PMID- 26304135
TI  - Successful Use of Maribavir for Drug-resistant Cytomegalovirus Colitis in a Heart
      Transplant Recipient.

PMID- 26304136
TI  - Familial Paralysis of the Atrium Due to a Mutation in SCN5A.

PMID- 26304137
TI  - Suspected lead poisoning in two captive cheetahs (Acinonyx jubatus jubatus) in
      South Africa, in 2008 and 2013.
AB  - Whilst lead poisoning in raptors, scavenging birds and waterfowl is well studied
      and common knowledge, there is surprisingly little literature detailing the risk
      to mammalian scavengers and captive carnivores fed hunted meat. This case report
      describes the death of two captive cheetahs (Acinonyx jubatus jubatus) following
      acute onset of nervous symptoms. Clinical signs included hyper-excitability,
      seizures, arched back, tail held abnormally high and hyper-salivation. Necropsy
      findings included bullets or a bullet in their stomachs. Kidney and liver lead
      levels from one cheetah (15.6 ppm and 17 ppm respectively) were consistent with a
      diagnosis of lead poisoning; liver from the second cheetah was not available for
      testing. Both animals were routinely fed hunted antelope or game birds. This is
      the first report of oral lead poisoning in captive large carnivores, although
      these are unlikely to be the first cases. Without awareness of the risks of
      feeding hunted game, lead exposure will continue to be an underdiagnosed reality
      in the rehabilitation of endangered carnivores. 

PMID- 26304138
TI  - Serum canine pancreatic-specific lipase concentrations in dogs with naturally
      occurring Babesia rossi infection.
AB  - Babesia rossi is the cause of a highly virulent multisystemic disease with a
      variable outcome, which is a reliable model of systemic inflammatory response
      syndrome (SIRS). The objective of this study was to determine the concentration
      of canine pancreatic-specific lipase (cPL) in a population of dogs with naturally
      acquired B. rossi infection. In addition, the associations between serum cPL and
      death and SIRS status were examined. An observational study recruited 87 dogs
      diagnosed with B. rossi infection and serum cPL concentrations were measured
      daily until discharge or death. The median concentration of serum cPL was 124.0
      ug/L (interquartile range: 51.0 ug/L - 475.5 ug/L) on admission (n = 87) and
      145.5 ug/L (62.3 ug/L - 434.0 ug/L) on day two of hospitalisation (n = 40).
      Twenty-four dogs (28%) had a serum cPL concentration within the diagnostic range
      for pancreatitis (> 400 ug/L) at admission with 13 dogs (32.5%) presenting as
      such on the second day of hospitalisation. The median concentration of serum cPL
      in dogs with SIRS was 158 ug/L (interquartile range: 52.5 ug/L - 571.5 ug/L; n =
      53), which was significantly higher than in those without SIRS (75 ug/L; 50.3
      ug/L - 131.8 ug/L; n = 32) (P = 0.018). This study demonstrated that an
      unexpectedly high number of dogs diagnosed with naturally acquired canine
      babesiosis had a serum cPL concentration within the diagnostic range for acute
      pancreatitis and a significantly higher serum cPL concentration was found in dogs
      that were classified as having SIRS. 

PMID- 26304139
TI  - Comparison of two culture techniques used to detect environmental contamination
      with Salmonella enterica in a large-animal hospital.
AB  - Salmonellosis is a common healthcare-associated infection in large-animal
      hospitals, and surveillance for Salmonella is an integral part of comprehensive
      infection control programmes in populations at risk. The present study compares
      the effectiveness of two culture techniques for recovery of Salmonella from
      environmental samples obtained in a large-animal referral veterinary hospital
      during a Salmonella outbreak. Environmental samples were collected using
      household cleaning cloths that were incubated overnight in buffered peptone water
      (BPW). Aliquots of BPW were then processed using two different selective
      enrichment and culture techniques. In the first technique (TBG-RV-XLT4) samples
      were incubated at 43  degrees C in tetrathionate broth and then Rappaport
      Vassiliadis broth before plating on XLT4 agar. The second technique (SEL-XLD)
      involved incubation at 37  degrees C in selenite broth before plating on XLD
      agar. Salmonella was recovered from 49.7% (73/147) of samples using the TBG-RV
      XLT4 technique, but only 10.2% (15/147) of samples using the SEL-XLD method.
      Fourteen samples (9.5%) were culture-positive using both methods, and 73 (49.7%)
      were culture-negative using both techniques. There were discordant results for 60
      samples, including 59 that were only culture-positive using the TBG-RV-XLT4
      method, and one sample that was only culture-positive using the SEL-XLD method.
      Salmonella was much more likely to be recovered using the TBG-RV-XLT4 method, and
      there appeared to be five times more false-negative results using the SEL-XLD
      technique. Environmental contamination with Salmonella may be underestimated by
      certain culture techniques, which may impair efforts to control spread in
      veterinary hospitals.

PMID- 26304141
TI  - Treatment of resistant port-wine stains with bosentan and pulsed dye laser: a
      pilot prospective study.

PMID- 26304140
TI  - Butorphanol with oxygen insufflation improves cardiorespiratory function in field
      immobilised white rhinoceros (Ceratotherium simum).
AB  - Opioid-induced immobilisation results in severe respiratory compromise in the
      white rhinoceros (Ceratotherium simum). The effectiveness of oxygen insufflation
      combined with butorphanol in alleviating respiratory depression in free-ranging
      chemically immobilised white rhinoceroses was investigated. In this prospective
      intervention study 14 free-ranging white rhinoceroses were immobilised with a
      combination of etorphine, azaperone and hyaluronidase. Six minutes (min) after
      the animals became recumbent, intravenous butorphanol was administered and oxygen
      insufflation was initiated. Previous boma trial results were used for comparison,
      using repeated measures two-way analysis of variance. The initial immobilisation
      induced hypoxaemia in free-ranging rhinoceroses (arterial partial pressure of
      oxygen [PaO2] 35.4 mmHg +/- 6.6 mmHg) was similar to that observed in boma
      confined rhinoceroses (PaO2 31 mmHg +/- 6 mmHg, n = 8). Although the initial
      hypercapnia (PaCO2 63.0 mmHg +/- 7.5 mmHg) was not as severe as that in animals
      in the boma trial (79 mmHg +/- 7 mmHg), the field-immobilised rhinoceroses were
      more acidaemic (pH 7.10 +/- 0.14) at the beginning of the immobilisation compared
      with boma-immobilised rhinoceroses (pH 7.28 +/- 0.04). Compared with pre
      intervention values, butorphanol with oxygen insufflation improved the PaO2 (81.2
      mmHg +/- 23.7 mmHg, p < 0.001, 5 min vs 20 min), arterial partial pressure of
      carbon dioxide (55.3 mmHg +/- 5.2 mmHg, p < 0.01, 5 min vs 20 min), pH (7.17 +/-
      0.11, p < 0.001, 5 min vs 20 min), heart rate (78 breaths/min +/- 20 breaths/min,
      p < 0.001, 5 min vs 20 min) and mean arterial blood pressure (105 mmHg +/- 14
      mmHg, p < 0.01, 5 min vs 20 min). Oxygen insufflation combined with a single
      intravenous dose of butorphanol improved oxygenation and reduced hypercapnia and
      acidaemia in immobilised free-ranging white rhinoceroses.

PMID- 26304142
TI  - Escalating incidence of eosinophilic esophagitis in Canton of Vaud, Switzerland,
      1993-2013: a population-based study.
AB  - BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic, inflammatory disease of
      the esophagus with a rapidly increasing incidence. However, population-based
      epidemiologic data on EoE are rare and limited to regions with less than 200,000
      inhabitants. We evaluated the incidence and prevalence of EoE over time in Canton
      of Vaud, Switzerland. MATERIALS AND METHODS: Canton of Vaud lies in the French
      speaking, Western part of Switzerland. As of December 2013, it had a population
      of 743,317 inhabitants. We contacted all pathology institutes (n = 6) in this
      canton to identify patients that have been diagnosed with esophageal eosinophilia
      between 1993 and 2013. We then performed a chart review in all adult and
      pediatric gastroenterology practices to identify patients with EoE. RESULTS: Of
      263 patients with esophageal eosinophilia, a total of 179 fulfilled the
      diagnostic criteria for EoE. Median diagnostic delay was 4 (IQR 1-9) years. No
      patient was diagnosed with EoE prior to 2003. Incidence of EoE increased from
      0.16/100,000 inhabitants in 2004 to 6.3/100,000 inhabitants in 2013 (P < 0.001).
      The cumulative EoE prevalence in 2013 was 24.1/100,000. The incidence in males
      was 2.8 times higher (95% CI 2.01-3.88, P < 0.001) when compared to that in
      females. The annual EoE incidence was 10.6 times higher (95%-CI 7.61-14.87, P <
      0.001) in the period from 2010 to 2013 when compared to that in the period from
      1993 to 2009. CONCLUSIONS: The incidence and cumulative prevalence of EoE in
      Canton of Vaud, Switzerland, has rapidly increased in the past 10 years.

PMID- 26304143
TI  - IMAGING DIAGNOSIS - MAGNETIC RESONANCE IMAGING OF INTRACRANIAL INFLAMMATORY
      FIBROSARCOMA IN A MIXED BREED DOG.
AB  - An 8-year-old mixed-breed dog presented with progressive behavioral changes and
      altered mentation. Magnetic resonance imaging (MRI) of the brain revealed an
      olfactory and frontal lobe extra-axial mass. The mass exhibited the following MRI
      signal intensity characteristics: T2W mixed, T1W iso- to hypointense, FLAIR
      hyperintense, and strong contrast enhancement. The mass was removed with
      cavitronic ultrasonic surgical aspirator (CUSA) assisted neurosurgery. Based on
      histopathological appearance and immunohistochemistry, the diagnosis of
      inflammatory fibrosarcoma was made. To our knowledge, this is the first report
      describing MRI characteristics of intracranial inflammatory fibrosarcoma in the
      veterinary literature. 

PMID- 26304144
TI  - Dizygotic monochorionic canine fetuses with blood chimaerism and suspected
      freemartinism.
AB  - Two full-term canine fetuses were found to share a placenta during Caesarean
      section. The fetuses were of discordant gender, with apparently normal male and
      female external genitalia. Genetic analysis of whole-blood samples obtained from
      each fetus revealed identical DNA profiles, with more than two alleles detected
      at six loci. Subsequent genetic analysis of myocardial tissue samples revealed
      dissimilar DNA profiles, with at most two alleles detected per locus.
      Superimposition of the tissue-derived profiles matched that derived from the
      blood samples exactly, except for two loci failing to amplify, and hence
      demonstrated blood chimaerism. Dissection of the abdomen of the male fetus
      revealed delayed descent of the testes towards the inguinal canals.
      Macroscopically, the gonads, uterus and vagina were not identifiable on
      dissection of the female fetus, although vestigial ovarian tissue and a vagina
      were detected microscopically. The hypoplastic internal reproductive tract of the
      female fetus was suggestive of freemartinism and is believed to be the first
      report of this condition in the canine.

PMID- 26304145
TI  - [Benchmarking and Quality Management Indicators Programme. Spanish experience].

PMID- 26304146
TI  - Brain. Editorial.

PMID- 26304147
TI  - Translating synaptic plasticity into sensation.

PMID- 26304148
TI  - Enhancing our understanding of white matter changes in early multiple sclerosis.

PMID- 26304149
TI  - GABA: a new imaging biomarker of neurodegeneration in multiple sclerosis?

PMID- 26304150
TI  - What is the function of auditory cortex without auditory input?

PMID- 26304152
TI  - PAP assays in newborn screening for cystic fibrosis: a population-based cost
      effectiveness study.
AB  - OBJECTIVES: To compare the cost effectiveness of adding a pancreatitis-associated
      protein (PAP) assay to common immunoreactive trypsinogen (IRT) and DNA cystic
      fibrosis (CF) newborn screening strategies. METHODS: Using data collected on
      553,167 newborns, PAP cut-offs were calculated based on non-inferiority of the
      detection rates of classical forms of CF. Cost effectiveness was considered from
      the third-party payer's perspective using only direct medical costs, and the unit
      costs of PAP assays were assessed based on a micro-costing study. Robustness of
      the cost-effectiveness estimates was assessed, taking the secondary outcomes of
      screening (ie. detecting mild forms and CF carriers) into account. RESULTS:
      IRT/DNA, IRT/PAP, and IRT/PAP/DNA strategies had similar detection rates for
      classical forms of CF, but the strategies involving PAP assays detected smaller
      numbers of mild forms of CF. The IRT/PAP strategy was cost-effective in
      comparison with either IRT/DNA or IRT/PAP/DNA. IRT/PAP/DNA screening was cost
      effective in comparison with IRT/DNA if relatively low value was assumed to be
      attached to the identification of CF carriers. CONCLUSIONS: IRT/PAP strategies
      could be strictly cost-effective, but dropping DNA would mean the test could not
      detect CF carriers. IRT/PAP/DNA strategies could be a viable option as they are
      significantly less costly than IRT/DNA, but still allow CF carrier detection.

PMID- 26304151
TI  - Reduced gamma-aminobutyric acid concentration is associated with physical
      disability in progressive multiple sclerosis.
AB  - Neurodegeneration is thought to be the major cause of ongoing, irreversible
      disability in progressive stages of multiple sclerosis. Gamma-aminobutyric acid
      is the principle inhibitory neurotransmitter in the brain. The aims of this study
      were to investigate if gamma-aminobutyric acid levels (i) are abnormal in
      patients with secondary progressive multiple sclerosis compared with healthy
      controls; and (ii) correlate with physical and cognitive performance in this
      patient population. Thirty patients with secondary progressive multiple sclerosis
      and 17 healthy control subjects underwent single-voxel MEGA-PRESS (MEscher
      GArwood Point RESolved Spectroscopy) magnetic resonance spectroscopy at 3 T, to
      quantify gamma-aminobutyric acid levels in the prefrontal cortex, right
      hippocampus and left sensorimotor cortex. All subjects were assessed clinically
      and underwent a cognitive assessment. Multiple linear regression models were used
      to compare differences in gamma-aminobutyric acid concentrations between patients
      and controls adjusting for age, gender and tissue fractions within each
      spectroscopic voxel. Regression was used to examine the relationships between the
      cognitive function and physical disability scores specific for these regions with
      gamma-aminobuytric acid levels, adjusting for age, gender, and total N-acetyl
      aspartate and glutamine-glutamate complex levels. When compared with controls,
      patients performed significantly worse on all motor and sensory tests, and were
      cognitively impaired in processing speed and verbal memory. Patients had
      significantly lower gamma-aminobutyric acid levels in the hippocampus (adjusted
      difference = -0.403 mM, 95% confidence intervals -0.792, -0.014, P = 0.043) and
      sensorimotor cortex (adjusted difference = -0.385 mM, 95% confidence intervals 
      0.667, -0.104, P = 0.009) compared with controls. In patients, reduced motor
      function in the right upper and lower limb was associated with lower gamma
      aminobutyric acid concentration in the sensorimotor cortex. Specifically for each
      unit decrease in gamma-aminobutyric acid levels (in mM), there was a predicted 
      10.86 (95% confidence intervals -16.786 to -4.482) decrease in grip strength (kg
      force) (P < 0.001) and -8.74 (95% confidence intervals -13.943 to -3.015)
      decrease in muscle strength (P < 0.006). This study suggests that reduced gamma
      aminobutyric acid levels reflect pathological abnormalities that may play a role
      in determining physical disability. These abnormalities may include decreases in
      the pre- and postsynaptic components of gamma-aminobutyric acid neurotransmission
      and in the density of inhibitory neurons. Additionally, the reduced gamma
      aminobutyric acid concentration may contribute to the neurodegenerative process,
      resulting in increased firing of axons, with consequent increased energy demands,
      which may lead to neuroaxonal degeneration and loss of the compensatory
      mechanisms that maintain motor function. This study supports the idea that
      modulation of gamma-aminobutyric acid neurotransmission may be an important
      target for neuroprotection in multiple sclerosis.See De Stefano and Giorgio
      (doi:10.1093/brain/awv213) for a scientific commentary on this article. 

PMID- 26304154
TI  - [Percutaneous interventions in cardiology in Poland in 2014. Summary report of
      the Association of Cardiovascular Interventions of the Polish Cardiac Society
      (AISN PTK)].

PMID- 26304153
TI  - From perceptual to lexico-semantic analysis--cortical plasticity enabling new
      levels of processing.
AB  - Certain kinds of stimuli can be processed on multiple levels. While the neural
      correlates of different levels of processing (LOPs) have been investigated to
      some extent, most of the studies involve skills and/or knowledge already present
      when performing the task. In this study we specifically sought to identify neural
      correlates of an evolving skill that allows the transition from perceptual to a
      lexico-semantic stimulus analysis. Eighteen participants were trained to decode
      12 letters of Morse code that were presented acoustically inside and outside of
      the scanner environment. Morse code was presented in trains of three letters
      while brain activity was assessed with fMRI. Participants either attended to the
      stimulus length (perceptual analysis), or evaluated its meaning distinguishing
      words from nonwords (lexico-semantic analysis). Perceptual and lexico-semantic
      analyses shared a mutual network comprising the left premotor cortex, the
      supplementary motor area (SMA) and the inferior parietal lobule (IPL). Perceptual
      analysis was associated with a strong brain activation in the SMA and the
      superior temporal gyrus bilaterally (STG), which remained unaltered from pre and
      post training. In the lexico-semantic analysis post learning, study participants
      showed additional activation in the left inferior frontal cortex (IFC) and in the
      left occipitotemporal cortex (OTC), regions known to be critically involved in
      lexical processing. Our data provide evidence for cortical plasticity evolving
      with a learning process enabling the transition from perceptual to lexico
      semantic stimulus analysis. Importantly, the activation pattern remains task
      related LOP and is thus the result of a decision process as to which LOP to
      engage in.

PMID- 26304155
TI  - 2015 guidelines for the management of hypertension. Recommendations of the Polish
      Society of Hypertension - short version.

PMID- 26304156
TI  - Randomized study of sequential cisplatin-topotecan/carboplatin-paclitaxel versus
      carboplatin-paclitaxel: effects on quality of life.
AB  - BACKGROUND: A recent phase III trial compared the efficacy of cisplatin-topotecan
      (a topoisomerase I inhibitor) followed by carboplatin-paclitaxel (Arm 1) versus
      paclitaxel-carboplatin (Arm 2) in women with newly diagnosed stage IIB or greater
      ovarian cancer. There was a significantly lower response rate in the experimental
      arm compared to standard treatment, and less likelihood of normalized CA125
      within the first 3 months. At 43 months follow-up, there were no significant
      group differences in progression-free survival. There were also significantly
      more side effects in the experimental arm. METHODS: The current study examined
      quality of life (QoL) endpoints using the European Organization for Research and
      Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) and the
      ovarian cancer module, QLQ-OV28, administered prior to randomization, at day 1 of
      treatment cycles 3, 5, and 7, at completion of the last cycle, and at 3 and 6
      months following completion of chemotherapy. RESULTS: Global QoL, physical
      symptoms, fatigue, and role, emotional, cognitive and social function (all from
      the EORTC QLQ-C30) significantly improved in both treatment arms, with no
      significant between-arm differences. Between-group differences in pain, insomnia,
      and peripheral neuropathy reported while on treatment did not differ at follow
      up. Nausea and vomiting improved more with standard treatment both during and
      after treatment. Body image significantly differed between the groups only at
      cycle 5 (more deterioration in Arm 2) but group differences disappeared at follow
      up. A stratified analysis of global QoL by debulking surgery status found no
      greater effect indicating that overall improvements in QoL were unrelated to
      surgical recovery. CONCLUSIONS: There was no significant QoL advantage of
      cisplatin-topotecan. This finding, combined with no progression-free survival
      conferred by this combination, reaffirms carboplatin-paclitaxel as the standard
      of care for women with newly diagnosed ovarian cancer.

PMID- 26304157
TI  - The cultural constructs of cancer-related fatigue among American Indian cancer
      survivors.
AB  - PURPOSE: Cancer-related fatigue (CRF) is a common symptom experienced by cancer
      survivors. Persistent fatigue can last years after cancer treatment. CRF's origin
      is unknown, and there are no validated treatments. Cultural constructs
      (definitions, meaning, and explanations) may vary the presentation and treatment
      choices related to fatigue. Identifying and categorizing CRF terms and
      experiences among racial, ethnic, and non-English speaking groups may provide a
      fuller understanding of CRF to guide tailoring of interventions. We report on the
      cultural constructs of CRF as reported by American Indian cancer survivors.
      METHODS: A study of Southwest American Indians collected qualitative data on
      cancer survivors' experiences of fatigue. Focus groups (n = 132) at urban clinics
      and rural reservation sites in the Southwest collected qualitative data on cancer
      survivor experiences with fatigue. The sessions were audiotaped and transcribed
      verbatim. During analysis, common themes were coded and formed into categories
      following Grounded Theory analytical procedures. Relationships between categories
      were examined. RESULTS: CRF was described by survivors as an entity that comes
      into the brain, "drains life" from the body, and creates long-lasting suffering,
      pain, and stigma. We review the cultural constructs of fatigue and CRF's
      relationship to "being out of balance." CONCLUSIONS: There is a need for
      culturally appropriate education concerning fatigue, techniques for reducing
      fatigue, and support for American Indian cancer survivors and other vulnerable
      populations.

PMID- 26304158
TI  - Evaluation of a weekly speech pathology/dietetic service model for providing
      supportive care intervention to head and neck cancer patients and their carers
      during (chemo)radiotherapy.
AB  - PURPOSE: Dysphagia is a common and debilitating side effect for head and neck
      cancer (HNC) patients undergoing radiotherapy (RT) with or without chemotherapy
      ([C]RT) and is associated with nutritional and emotional comorbidities. Emotional
      sequelae and distress are also known to affect carers of HNC patients. A weekly,
      joint speech pathology/dietetic (SP/DN) service-delivery model has been employed
      to manage swallowing/nutritional and associated emotional issues during (C)RT.
      This study aimed to conduct a service evaluation of the weekly SP/DN clinical
      model. METHODS: Cross-sectional sampling of core service metrics and perceptions
      of key stakeholders (70 HNC patients, 30 carers, and 10 clinicians) were collated
      from the Metro South Radiation Oncology Service in Brisbane, Australia. Data from
      each source was examined separately and then triangulated. RESULTS: An average of
      28 patients (SD = 5.54) attended SP/DN appointments per week, with 58% reporting
      swallowing and/or nutritional issues. Distress was reported by 27% of patients
      and 30% of carers. Clinicians felt able to adequately identify and manage
      swallowing and nutrition 90% of the time but only 10% of the time for distress.
      Seventy-six percent of scheduled SP/DN sessions were perceived as necessary by
      either patients, clinicians or both. CONCLUSIONS: Findings demonstrated a third
      of patients and their carers had a high level of distress during HNC [C]RT,
      supporting need for the provision of a weekly SP/DN service in a select cohort.
      However, the routine weekly SP/DN assessment model for all patients undergoing
      HNC treatment demonstrates the potential for over-servicing. Alternative service
      delivery models warrant further evaluation.

PMID- 26304159
TI  - Squamous cell carcinoma of the lip: depth of invasion, local recurrence and
      regional metastases. Experience of a rural multidisciplinary head and neck unit.
AB  - BACKGROUND: The internationally recognised American Joint Committee on Cancer
      (tumour-node-metastasis) staging system utilises tumour size to determine stage.
      Other factors (i.e. tumour depth) may provide additional prognostic information.
      METHOD: A thorough retrospective analysis was performed of 68 patients with
      primary lip squamous cell carcinoma operated on or discussed by the Darling Downs
      Health Service between 2005 and 2013. RESULTS: Twelve patients developed
      lymphatic spread. There was a statistically significant increased risk of nodal
      metastasis in: patients with tumours of increased thickness (U = 103.50; degrees
      of freedom = 68; p < 0.001), those with a larger overall tumour size (U = 163.50;
      degrees of freedom = 68; p = 0.005) and patients living further from the
      treatment centre (U = 199.00; degrees of freedom = 68; p = 0.018). CONCLUSION: It
      may be reasonable that other factors are considered for staging of lip squamous
      cell carcinomas, in combination with tumour-node-metastasis staging. Depth of
      invasion may have utility in prognosis and treatment; however, larger prospective
      analysis needs to be performed. Patients living in a more rural setting presented
      with more advanced disease, suggesting an ongoing rural-metropolitan gap in
      healthcare.

PMID- 26304160
TI  - Total Aortic Arch Reconstruction With Triple-Branched Stent Graft or Hemiarch
      Replacement for Acute Debakey Type I Aortic Dissection: Five-Years Experience
      With 93 Patients.
AB  - OBJECTIVE: We compared the outcomes of a new triple-branched stent graft
      reconstruction technique of total aortic arch with those of the conventional
      strategy of replacing the hemiarch during the surgical treatment of acute Debakey
      type I aortic dissection over five years. METHODS: Fifty-two patients with acute
      Debakey type I aortic dissection underwent ascending aorta replacement combined
      with triple-branched stent graft reconstruction of the aortic arch from June 2008
      to February 2010. Concurrently, 41 cases of Debakey type I aortic dissection
      underwent ascending aorta replacement combined with hemiarch replacement. Both
      groups received hypothermic cardiopulmonary bypass and selective cerebral
      perfusion. RESULTS: Patient characteristics and in-hospital mortality of the two
      groups were similar. Postoperative data were not different between the groups.
      During the five years after surgery, there were no deaths in the stent graft
      group and three deaths in the hemiarch group. The late reinterventions/events
      during follow-up in the stent graft group were significantly less than those in
      the hemiarch group. On postoperative computed tomography, the aortic diameter of
      both groups was significantly reduced compared to the postoperative aortic
      diameter. There was no difference in diameter between one month and five years
      postoperatively in the stent graft group, although in the hemiarch group the
      diameter was significantly greater at five years than at one month
      postoperatively. CONCLUSION: The triple-branched stent graft reconstruction of
      the aortic arch is an effective and simplified procedure for the treatment of
      acute Debakey type I aortic dissection.

PMID- 26304161
TI  - Targeting Interleukin-1 beta to Suppress Sympathoexcitation in Hypothalamic
      Paraventricular Nucleus in Dahl Salt-Sensitive Hypertensive Rats.
AB  - Findings from our laboratory indicate that expressions of some proinflammatory
      cytokines such as tumor necrosis factor, interleukin-6 and oxidative stress
      responses are increased in the hypothalamic paraventricular nucleus (PVN) and
      contribute to the progression of salt-sensitive hypertension. In this study, we
      determined whether interleukin-1 beta (IL-1beta) activation within the PVN
      contributes to sympathoexcitation during development of salt-dependent
      hypertension. Eight-week-old male Dahl salt-sensitive (S) rats received a high
      salt diet (HS, 8 % NaCl) or a normal-salt diet (NS, 0.3 % NaCl) for 6 weeks, and
      all rats were treated with bilateral PVN injection of gevokizumab (IL-1beta
      inhibitor, 1 MUL of 10 MUg) or vehicle once a week. The mean arterial pressure
      (MAP), heart rate (HR) and plasma norepinephrine (NE) were significantly
      increased in high-salt-fed rats. In addition, rats with high-salt diet had higher
      levels of NOX-2, NOX-4 [subunits of NAD (P) H oxidase], IL-1beta, NLRP3 (NOD-like
      receptor family pyrin domain containing 3), Fra-LI (an indicator of chronic
      neuronal activation) and lower levels of IL-10 in the PVN than normal-diet rats.
      Bilateral PVN injection of gevokizumab decreased MAP, HR and NE, attenuated the
      levels of oxidative stress and restored the balance of cytokines. These findings
      suggest that IL-1beta activation in the PVN plays a role in salt-sensitive
      hypertension.

PMID- 26304164
TI  - Overexpression of CCT8 and its significance for tumor cell proliferation,
      migration and invasion in glioma.
AB  - Overexpression of chaperonin containing t-complex polypeptide 1 (TCP1), or CCT,
      has been reported in various classes of malignancies. However, little is known
      about the expression of t-complex protein subunits TCP1theta (CCT8) in gliomas.
      In this study, the expression of CCT8 protein was detected using blotting
      analysis and immunohistochemistry. CCT8 was found to be overexpressed in gliomas
      and to correlate with the WHO grade of gliomas. To further investigate the
      biological function of CCT8 in gliomas, CCT8-silenced U87 glioblastoma multiforme
      (GBM) and U251MG cells were constructed using a small interference RNA (siRNA)
      sequence. The knockdown effect of CCT8 on proliferation and invasion in these
      cells was analyzed using the CCK8, flow cytometry cycle, scratch, transwell
      invasion and fluorescence assays. Compared with the controls, the glioma cells
      expressing CCT8-siRNA exhibited a significantly decreased proliferation and
      invasion capacity, as well as a dysregulated cell cytoskeleton. This study showed
      that high CCT8 protein expression might be related to poor outcome of glioma, and
      that CCT8 regulates the proliferation and invasion of glioblastomas. 

PMID- 26304165
TI  - Anti-adhesion activity of thyme (Thymus vulgaris L.) extract, thyme post
      distillation waste, and olive (Olea europea L.) leaf extract against
      Campylobacter jejuni on polystyrene and intestine epithelial cells.
AB  - BACKGROUND: In order to survive in food-processing environments and cause
      disease, Campylobacter jejuni requires specific survival mechanisms, such as
      biofilms, which contribute to its transmission through the food chain to the
      human host and present a critical form of resistance to a wide variety of
      antimicrobials. RESULTS: Phytochemical analysis of thyme ethanolic extract (TE),
      thyme post-hydrodistillation residue (TE-R), and olive leaf extract (OE) using
      high-performance liquid chromatography with photodiode array indicates that the
      major compounds in TE and TE-R are flavone glucuronides and rosmarinic acid
      derivatives, and in OE verbascoside, luteolin 7-O-glucoside and oleuroside. TE
      and TE-R reduced C. jejuni adhesion to abiotic surfaces by up to 30% at 0.2-12.5
      ug mL(-1) , with TE-R showing a greater effect. OE from 3.125 to 200 ug mL(-1)
      reduced C. jejuni adhesion to polystyrene by 10-23%. On the other hand, C. jejuni
      adhesion to PSI cl1 cells was inhibited by almost 30% over a large concentration
      range of these extracts. CONCLUSION: Our findings suggest that TE, the agro-food
      waste material TE-R, and the by-product OE represent sources of bioactive
      phytochemicals that are effective at low concentrations and can be used as
      therapeutic agents to prevent bacterial adhesion. (c) 2015 Society of Chemical
      Industry.

PMID- 26304166
TI  - Cystic echinococcosis amongst small ruminants and humans in central Ethiopia.
AB  - This study was conducted to determine the prevalence of cystic echinococcosis
      (CE) in small ruminants and humans in Addis Ababa, central Ethiopia. A cross
      sectional study involving systematic random sampling was conducted to estimate
      the prevalence of CE in 512 small ruminants (262 sheep and 250 goats) slaughtered
      at Addis Ababa Abattoir Enterprise between October 2011 and March 2012. Hydatid
      cysts were identified macroscopically during postmortem examination and their
      fertility and viability were determined. CE was observed in 21 (8.02%) sheep and
      17 (6.80%) goats. In sheep 13 (4.96%) of the lungs, 10 (3.81%) livers and 1
      (0.381%) heart were found to be infected with hydatid cysts. Involvement of lung
      and liver in goats was found to be 10 (4.0%) and 8 (3.2%) respectively, with no
      cysts recorded in the heart. Of the total of 77 and 47 cysts encountered in sheep
      and goats, 33 (42.85%) and 15 (31.91%) respectively were fertile. Viability of
      protoscoleces from fertile cysts in sheep (29 [87.87%]) was higher than in goats
      (6 [40.0%]). For humans, retrospective analysis covering five years of case
      reports at two major hospitals in Addis Ababa between January 2008 and December
      2012 showed that of the total of 25 840 patients admitted for ultrasound
      examination, 27 CE cases were registered, a prevalence of 0.1% and mean annual
      incidence rate of approximately 0.18 cases per 100 000 population. Liver was the
      major organ affected in humans (81.5% in affected patients) followed by spleen
      (11.1%) and kidney (7.4%). Logistic regression analysis showed that prevalence of
      CE varied significantly in relation to host age in the small ruminants (OR =
      3.93, P < 0.05) as well as in humans (95% CI, R = 4.8). This epidemiological
      study confirms the importance of CE in small ruminants and humans in central
      Ethiopia, emphasising the need for integrated approaches to controlling this
      neglected preventable disease. 

PMID- 26304167
TI  - Pre-slaughter, slaughter and post-slaughter defects of skins and hides at the
      Sheba Tannery and Leather Industry, Tigray region, northern Ethiopia.
AB  - Skins and hides are perishable resources that can be damaged by parasitic
      diseases and human error, which result in downgrading or rejection. This study
      was conducted to identify defect types and to determine their prevalence in
      pickled sheep and wet blue goat skins and wet blue hides. Each selected skin or
      hide was examined for defects in natural light and the defects were graded
      according to established quality criteria in Ethiopian standard manuals. Major
      defects were captured by digital photography. The major pre-slaughter defects
      included scratches (64.2%), cockle (ekek) (32.8%), wounds or scars (12.6%),
      lesions from pox or lumpy skin disease (6.1%), poor substance (5%), branding
      marks (2.3%) and tick bites (1.5%). The presence of grain scratches in wet blue
      hides (76.3%) was significantly higher than in pickled sheep (67.2%) and wet blue
      goat (59.1%) skins. The major slaughter defects included flay cuts or scores,
      holes, poor pattern and vein marks, with a higher occurrence in wet blue goat
      skins (28.7%; P < 0.001) than in wet blue hides (22.8%) and pickled sheep skins
      (11.1%). The most prevalent postslaughter defects were grain cracks (14.9%), hide
      beetle damage (8%), damage caused by heat or putrefaction (3.7%) and machine
      induced defects (0.5%). Grain cracks (27.04%) and hide beetle damage (13.9%) in
      wet blue goat skins were significantly more common than in wet blue hides and
      pickled sheep skins. These defects cause depreciation in the value of the hides
      and skins. Statistically significant (P < 0.001) higher rejection rates were
      recorded for wet blue hides (82.9%) than for pickled sheep skins (18.3%) and wet
      blue goat skins (8.5%). Improved animal health service delivery, effective
      disease control strategies and strong collaboration between stakeholders are
      suggested to enhance the quality of skins and hides. 

PMID- 26304162
TI  - The expanded genetic alphabet.
AB  - All biological information, since the last common ancestor of all life on Earth,
      has been encoded by a genetic alphabet consisting of only four nucleotides that
      form two base pairs. Long-standing efforts to develop two synthetic nucleotides
      that form a third, unnatural base pair (UBP) have recently yielded three
      promising candidates, one based on alternative hydrogen bonding, and two based on
      hydrophobic and packing forces. All three of these UBPs are replicated and
      transcribed with remarkable efficiency and fidelity, and the latter two thus
      demonstrate that hydrogen bonding is not unique in its ability to underlie the
      storage and retrieval of genetic information. This Review highlights these recent
      developments as well as the applications enabled by the UBPs, including the
      expansion of the evolution process to include new functionality and the creation
      of semi-synthetic life that stores increased information. 

PMID- 26304168
TI  - Peste des petits ruminants outbreaks in White Nile State, Sudan.
AB  - Eight outbreaks of peste des petits ruminants in sheep and goats were reported in
      White Nile State, Sudan, between 2008 and 2009. A mortality rate of 4.2% was
      reported across the different outbreaks. Clinically the disease was characterised
      by high fever, ocular and nasal discharge, pneumonia, ulceration of the mucous
      membranes, diarrhoea and death. The postmortem findings included necrotic lesions
      in the mouth and gastrointestinal tract, and swollen, oedematous lymph nodes
      associated with the lungs and intestine. Of the 209 serum samples tested by
      competitive enzyme-linked immunosorbent assay, 113 (54%) were found positive.
      Peste des petits ruminants virus was confirmed in tissues, nasal swabs and blood
      samples by immunocapture enzyme-linked immunosorbent assay, reverse-transcription
      polymerase chain reaction and isolation of the virus in culture of lamb testicle
      cells. 

PMID- 26304169
TI  - The slaughter of increased numbers of pregnant cows in Tanga abattoir, Tanzania:
      A cause for concern?
AB  - Information on the level of foetal wastage in slaughtered cattle in Tanzania is
      limited. A three-month observational study (April - June 2014) of animals
      slaughtered at the Tanga abattoir in Tanga region, Tanzania was carried out to
      determine the number of pregnant cows slaughtered. The total number of cattle
      slaughtered during the study period was 3643, representing a monthly kill average
      of 1214 and a daily kill average of 40. Over 98% of the cattle presented to the
      abattoir for slaughter were local breed (Tanzania shorthorn zebu) and most were
      above 3 years of age. Improved breeds of cattle represented only 1.3% of all
      slaughters. Of the cattle slaughtered, 2256 (61.9%) were female and 1387 (38.1%)
      were male. A total of 655 slaughtered cows were pregnant, representing a foetal
      wastage of 29.1%. Of the 655 recovered foetuses, 333 (50.8%) were male and 322
      (49.2%) were female. Of the recovered foetuses, 25.8% were recovered in the
      first, 42.7% in the second and 31.6% in the third trimester. This study indicates
      cases of significant foetal losses, negatively impacting future replacement stock
      as a result of the slaughter of pregnant animals. The indiscriminate slaughter of
      pregnant cows suggests that existing animal welfare legislation is not
      sufficiently enforced and routine veterinary ante-mortem inspection of trade
      animals is failing to prevent the high level of foetal wastage. 

PMID- 26304170
TI  - Lymph node metastasis risk according to the depth of invasion in early gastric
      cancers confined to the mucosal layer.
AB  - BACKGROUND: Early gastric cancers (EGCs) within the mucosal layer of the gastric
      wall have a small risk of lymph node (LN) metastasis. METHODS: We reviewed
      clinicopathology data for patients who underwent surgery for EGC between 2001 and
      2013 at the National Cancer Center, Korea. Poisson regression analyses were
      performed to compare the risk of LN metastasis according to the depth of tumor
      invasion in patients with mucosal EGCs. RESULTS: Among the 1776 EGC patients
      included, 580 (32.7 %) had tumors confined to the lamina propria (LP; LP group)
      and 1196 (67.3 %) had tumors invading the muscularis mucosae (MM; MM group).
      Seventy-one patients (4.0 %) had LN metastasis, and the MM group had a
      significantly higher rate of LN metastasis (59 patients, 4.9 %) than the LP group
      (12 patients, 2.1 %; P = 0.004). A multivariate analysis showed that tumors
      invading the MM (adjusted risk ratio 1.95; P = 0.045) were significantly
      associated with LN metastasis in addition to well-known risk factors, including
      tumor size greater than 3 cm, presence of ulceration, undifferentiated histologic
      type, and lymphovascular invasion. The incidence of LN metastasis was 1.87 % (95
      % confidence interval 0.23-6.59 %) within tumors invading the MM that met the
      expanded criterion for endoscopic resection of differentiated histologic type of
      size 3 cm or smaller with ulceration. LN metastasis was not found in tumors
      meeting the absolute criteria for endoscopic resection. CONCLUSIONS: EGCs
      invading the MM had a higher rate of lymph node metastasis than those confined to
      the LP. Further study is needed to evaluate whether different curative treatment
      criteria are needed for LP-confined and MM-invading EGCs.

PMID- 26304172
TI  - Pain.
AB  - Pain has many valuable functions. It often signals injury or disease, generates a
      wide range of adaptive behaviors, and promotes healing through rest. Despite
      these beneficial aspects of pain, there are negative features that challenge our
      understanding of the puzzle of pain, including persistent phantom limb pain after
      amputation or total spinal cord transection. Pain is a personal, subjective
      experience influenced by cultural learning, the meaning of the situation,
      attention, and other psychological variables. Pain processes do not begin with
      the stimulation of receptors. Rather, injury or disease produces neural signals
      that enter an active nervous system that (in the adult organism) is the substrate
      of past experience, culture, and a host of other environmental and personal
      factors. These brain processes actively participate in the selection,
      abstraction, and synthesis of information from the total sensory input. Pain is
      not simply the end product of a linear sensory transmission system; it is a
      dynamic process that involves continuous interactions among complex ascending and
      descending systems. The neuromatrix theory guides us away from the Cartesian
      concept of pain as a sensation produced by injury, inflammation, or other tissue
      pathology and toward the concept of pain as a multidimensional experience
      produced by multiple influences. These influences range from the existing
      synaptic architecture of the neuromatrix-which is determined by genetic and
      sensory factors-to influences from within the body and from other areas in the
      brain. Genetic influences on synaptic architecture may determine-or predispose
      toward-the development of chronic pain syndromes. WIREs Cogn Sci 2013, 4:1-15.
      doi: 10.1002/wcs.1201 For further resources related to this article, please visit
      the WIREs website. 

PMID- 26304173
TI  - Cognitive engineering.
AB  - Cognitive engineering is the application of cognitive psychology and related
      disciplines to the design and operation of human-machine systems. Cognitive
      engineering combines both detailed and close study of the human worker in the
      actual work context and the study of the worker in more controlled environments.
      Cognitive engineering combines multiple methods and perspectives to achieve the
      goal of improved system performance. Given the origins of experimental psychology
      itself in issues regarding the design of human-machine systems, cognitive
      engineering is a core, or fundamental, discipline within academic psychology.
      WIREs Cogn Sci 2013, 4:17-31. doi: 10.1002/wcs.1204 CONFLICT OF INTEREST: The
      authors declare no conflict of interest. For further resources related to this
      article, please visit the WIREs website. 

PMID- 26304171
TI  - Development of an S-1 dosage formula based on renal function by a prospective
      pharmacokinetic study.
AB  - BACKGROUND: S-1 is an oral anticancer drug, containing tegafur (a prodrug of 5
      fluorouracil, 5-FU), 5-chloro-2,4-dihydroxypyridine, and potassium oxonate. As
      renal dysfunction is known to increase exposure of 5-FU following S-1
      administration, the incidence of severe adverse reactions is increased in
      patients with impaired renal function. However, no reliable information on its
      dose modification for patients with renal dysfunction has been provided. METHODS:
      We conducted a prospective pharmacokinetic study to develop an S-1 dosage formula
      based on renal function. Sixteen cancer patients with various degrees of renal
      function received a single dose of S-1 at 40 mg/m(2). A series of blood samples
      were collected at predefined times within 24 h to assess the plasma concentration
      profiles of 5-FU, 5-chloro-2,4-dihydroxypyridine, and tegafur. A mathematical
      model for the relationship between renal function and exposure of 5-FU was
      constructed by a population pharmacokinetic analysis. RESULTS: The clearance of 5
      FU following S-1 administration was related to body surface area and creatinine
      clearance in the range 15.9-108.8 mL/min as estimated by the Cockcroft-Gault
      equation. The S-1 dosage formula was derived as follows:[Formula: see text]where
      AUC is the area under the concentration-time curve, CLcr is creatinine clearance,
      and BSA is body surface area. The recommended daily doses of S-1 in Asia and
      Europe were also proposed as nomograms according to exposure matching to the
      previously reported area under the concentration-time curve of 5-FU, which
      confirmed the efficacy and toxicity in pivotal registration studies. CONCLUSIONS:
      We have developed a novel formula for determining the S-1 dosage on the basis of
      renal function. Further validation is needed to confirm the formula for practical
      application.

PMID- 26304174
TI  - The retreat from overgeneralization in child language acquisition: word learning,
      morphology, and verb argument structure.
AB  - This review investigates empirical evidence for different theoretical proposals
      regarding the retreat from overgeneralization errors in three domains: word
      learning (e.g., *doggie to refer to all animals), morphology [e.g., *spyer,
      *cooker (one who spies/cooks), *unhate, *unsqueeze, *sitted; *drawed], and verb
      argument structure [e.g., *Don't giggle me (c.f. Don't make me giggle); *Don't
      say me that (c.f. Don't say that to me)]. The evidence reviewed provides support
      for three proposals. First, in support of the pre-emption hypothesis, the
      acquisition of competing forms that express the desired meaning (e.g., spy for
      *spyer, sat for *sitted, and Don't make me giggle for *Don't giggle me) appears
      to block errors. Second, in support of the entrenchment hypothesis, repeated
      occurrence of particular items in particular constructions (e.g., giggle in the
      intransitive construction) appears to contribute to an ever strengthening
      probabilistic inference that non-attested uses (e.g., *Don't giggle me) are
      ungrammatical for adult speakers. That is, both the rated acceptability and
      production probability of particular errors decline with increasing frequency of
      pre-empting and entrenching forms in the input. Third, learners appear to acquire
      semantic and morphophonological constraints on particular constructions,
      conceptualized as properties of slots in constructions [e.g., the (VERB) slot in
      the morphological un-(VERB) construction or the transitive-causative (SUBJECT)
      (VERB) (OBJECT) argument-structure construction]. Errors occur as children
      acquire the fine-grained semantic and morphophonological properties of particular
      items and construction slots, and so become increasingly reluctant to use items
      in slots with which they are incompatible. Findings also suggest some role for
      adult feedback and conventionality; the principle that, for many given meanings,
      there is a conventional form that is used by all members of the speech community.
      WIREs Cogn Sci 2013, 4:47-62. doi: 10.1002/wcs.1207 For further resources related
      to this article, please visit the WIREs website. CONFLICT OF INTEREST: The
      authors declare no conflict of interest.

PMID- 26304175
TI  - The complex act of projecting oneself into the future.
AB  - Research on future-oriented mental time travel (FMTT) is highly active yet
      somewhat unruly. I believe this is due, in large part, to the complexity of both
      the tasks used to test FMTT and the concepts involved. Extraordinary care is a
      necessity when grappling with such complex and perplexing metaphysical constructs
      as self and time and their co-instantiation in memory. In this review, I first
      discuss the relation between future mental time travel and types of memory
      (episodic and semantic). I then examine the nature of both the types of self
      knowledge assumed to be projected into the future and the types of temporalities
      that constitute projective temporal experience. Finally, I argue that a person
      lacking episodic memory should nonetheless be able to imagine a personal future
      by virtue of (1) the fact that semantic, as well as episodic, memory can be self
      referential, (2) autonoetic awareness is not a prerequisite for FMTT, and (3)
      semantic memory does, in fact, enable certain forms of personally oriented FMTT.
      WIREs Cogn Sci 2013, 4:63-79. doi: 10.1002/wcs.1210 For further resources related
      to this article, please visit the WIREs website. 

PMID- 26304176
TI  - Cognitive aspects of fetal alcohol spectrum disorder.
AB  - Nearly four decades have passed since a link was first established between
      alcohol consumption during pregnancy and a particular pattern of birth defects.
      Since then, autopsy, longitudinal, structural imaging, and functional imaging
      studies have revealed a great deal about the teratogenic effects of alcohol. This
      paper provides a comprehensive summary of the findings from the neurocognitive
      and behavioral literature on fetal alcohol spectrum disorder (FASD) and outlines
      the unique profile of cognitive deficits associated with it. We describe
      diagnostic issues as well as factors contributing to the heterogeneity of the
      FASD cognitive presentation. Next, we review research on the impact of prenatal
      alcohol exposure on intellectual functioning, attention, executive functioning,
      learning and memory, language, quantitative reasoning, and social cognition. In
      our opinion, future research can now begin to focus on FASD-specific
      interventions directly informed by the rich body of neurocognitive findings
      accumulated thus far. WIREs Cogn Sci 2013, 4:81-92. doi: 10.1002/wcs.1202 For
      further resources related to this article, please visit the WIREs website. 

PMID- 26304177
TI  - Epigenetic mechanisms in learning and memory.
AB  - Recent discoveries have associated epigenetic mechanisms, including DNA
      methylation, histone modifications, and microRNA (miRNA) processing, with
      activity-dependent changes in gene expression necessary to drive long-term memory
      formation. Here, we discuss the current interpretation of epigenetic mechanisms
      in the context of memory and sustained behavioral change. One of the two emerging
      viewpoints is that epigenetic mechanisms subserve information storage in the
      central nervous system (CNS), a notion supported by rodent studies of fear,
      recognition and spatial memories, and stress. The second viewpoint is that
      epigenetics serves as a mechanism for passing on acquired information across
      generations, a provocative notion now supported by several lines of work using
      developing and adult rodents. Continued research on such mechanisms promises to
      advance our understanding of biological pathways linking experiences to long-term
      and even multigenerational trajectories in neurobiology and behavior. WIREs Cogn
      Sci 2013, 4:105-115. doi: 10.1002/wcs.1205 For further resources related to this
      article, please visit the WIREs website. 

PMID- 26304178
TI  - Combinatorial effects of epidermal growth factor, fibroblast growth factor 2 and
      insulin-like growth factor 1 on trophoblast cell proliferation and embryogenesis
      in cattle.
AB  - Uterine secretions are crucial for conceptus development in mammals. This is
      especially important for species that undergo extended preimplantation
      development, like cattle and other ungulates. The present study examined
      cooperative interactions for epidermal growth factor (EGF), fibroblast growth
      factor-2 (FGF2) and insulin-like growth factor-1 (IGF1) on the proliferation of
      the bovine trophoblast cell line CT1 and bovine embryo development. Proliferation
      of CT1 cells increased after supplementation of the culture medium with 10ngmL-1
      EGF, 10ngmL-1 FGF2 or 50ngmL-1 IGF1, as well as with any combination of two
      factors. Greater increases in CT1 cell proliferation were detected when the
      growth medium was supplemented with all three factors. Supplementing the culture
      medium with individual or multiple factors during bovine embryo culture resulted
      in several positive outcomes, including increased blastocyst development,
      expansion, and hatching to varying degrees depending on the particular factor or
      combination of factors. Supplementation of the culture medium with all three
      factors increased embryonic trophoblast cell numbers on Day 8, as well as
      hatching rates and blastocyst diameter on Day 12 after fertilisation. Western
      blot analyses and the use of pharmacological inhibitors suggest that EGF and IGF1
      affect CT1 proliferation by activating mitogen-activated protein kinase 3/1,
      whereas FGF2 activates AKT. In conclusion, the findings of the present study
      indicate that there are cooperative interactions among EGF, FGF2 and IGF1 that
      enhance trophoblast cell development during early embryogenesis.

PMID- 26304179
TI  - [Primary care in France].
AB  - The poor planning of health care professionals in Spain has led to an exodus of
      doctors leaving the country. France is one of the chosen countries for Spanish
      doctors to develop their professional career. The French health care system
      belongs to the Bismarck model. In this model, health care system is financed
      jointly by workers and employers through payroll deduction. The right to health
      care is linked to the job, and provision of services is done by sickness-funds
      controlled by the Government. Primary care in France is quite different from
      Spanish primary care. General practitioners are independent workers who have the
      right to set up a practice anywhere in France. This lack of regulation has
      generated a great problem of "medical desertification" with problems of health
      care access and inequalities in health. French doctors do not want to work in
      rural areas or outside cities because "they are not value for money". Medical
      salary is linked to professional activity. The role of doctors is to give
      punctual care. Team work team does not exist, and coordination between primary
      and secondary care is lacking. Access to diagnostic tests, hospitals and
      specialists is unlimited. Duplicity of services, adverse events and
      inefficiencies are the norm. Patients can freely choose their doctor, and they
      have a co-payment for visits and hospital care settings. Two years training is
      required to become a general practitioner. After that, continuing medical
      education is compulsory, but it is not regulated. Although the French medical
      Health System was named by the WHO in 2000 as the best health care system in the
      world, is it not that good. While primary care in Spain has room for improvement,
      there is a long way for France to be like Spain. 

PMID- 26304180
TI  - More is needed by all for transparency in clinical research.

PMID- 26304181
TI  - Effect of combining a health program with a microfinance-based self-help group on
      health behaviors and outcomes.
AB  - OBJECTIVES: Women's participation in microfinance-based self-help groups (SHGs)
      and the resultant social capital may provide a basis to address the gap in health
      attainment for poor women and their children. We investigated the effect of
      combining a health program designed to improve health behaviours and outcomes
      with a microfinance-based SHG program. DESIGN: A mixed method study was conducted
      among 34 villages selected from three blocks or district subdivisions of India;
      one in Gujarat, two in Karnataka. METHODS: A set of 17 villages representing new
      health program areas were pair-matched with 17 comparison villages. Two rounds of
      surveys were conducted with a total of 472 respondents, followed by 17 key
      informant interviews and 17 focus group discussions. RESULTS: Compared to a
      matched comparison group, women in SHGs that received the health program had
      higher odds of delivering their babies in an institution (OR: 5.08, 95% CI 1.21
      21.35), feeding colostrum to their newborn (OR: 2.83, 95% CI 1.02-5.57), and
      having a toilet at home (OR: 1.53, 95% CI 0.76-3.09). However, while the change
      was in the expected direction, there was no statistically significant reduction
      in diarrhoea among children in the intervention community (OR: 0.86, 95% CI 0.42
      1.76), and the hypothesis that the health program would result in decreased out
      pocket expenditures on treatment was not supported. CONCLUSION: Our study found
      evidence that health programs implemented with microfinance-based SHGs is
      associated with improved health behaviours. With broad population coverage of
      SHGs and the social capital produced by their activities, microfinance-based SHGs
      may provide an avenue for addressing the health needs of poor women.

PMID- 26304182
TI  - Lower cognitive performance and white matter changes in testicular cancer
      survivors 10 years after chemotherapy.
AB  - OBJECTIVE: Chemotherapy (CT) is associated with adverse effects on cognition.
      Only few studies have investigated cognition in testicular cancer (TC) patients
      and studies on very late effects of CT on cognition are absent. Further, brain
      changes in relation to treatment have not been investigated in TC. The objective
      of the present study is to compare psychosocial functioning, cognitive
      performance and brain (micro)structure following surgery and CT for TC, against
      surgery (S)-only. METHODS: Twenty-eight CT (43.1+/-7.5 y) and 23 S-only (48.2+/
      9.5y) TC survivors on average 14 yr post-treatment were examined using
      questionnaires, neurocognitive tests, and 3T-MRI [Diffusion Kurtosis Imaging
      (DKI), T1-weighted and Fluid Attenuated Inversion Recovery]. A multivariate
      cognitive performance score (Mahalanobis distance) was calculated to indicate the
      grade of cognitive performance. Kurtosis parameters, gray matter, and white
      matter (WM) volume were calculated from MRI data. RESULTS: Overall, the CT group
      showed lower cognitive performance (5.35+/-1.7) compared with the S-only group
      (4.4+/-0.9; P=0.03; d=0.70). Further, TC patients reported more memory problems
      after CT. DKI revealed a significantly higher radial kurtosis after CT in several
      anterior and posterior brain areas (P<0.05, corrected), but this was unrelated to
      cognitive performance. CONCLUSIONS: This cross-sectional study suggests that men
      receiving CT for TC are at risk for long-term lower cognitive performance.
      Although CT affected WM microstructure, this was unrelated to cognitive
      performance. More extensive, preferably prospective studies are warranted to
      confirm these results and to provide more insight into the possible mechanisms
      behind the observed cognitive sequelae after treatment for TC.

PMID- 26304183
TI  - Bariatric Centers of Excellence: Effect of Centralization on Access to Care.
AB  - BACKGROUND: In 2006, the Centers for Medicare and Medicaid Services restricted
      coverage for bariatric procedures to designated high-volume Centers of
      Excellence. The effect of centralization of elective surgical procedures on the
      ability of patients to access surgery has not been studied previously. STUDY
      DESIGN: Inpatient claims data from 2008 to 2011 from 2 high-volume surgical
      states were used. All patients older than 18 years undergoing a bariatric
      surgical procedure were included. The number of bariatric procedures and
      characteristics of patients undergoing bariatric surgery were examined in each
      year. Nonparametric tests for trend were performed to analyze time trends.
      Difference-in-difference analyses were performed to assess the rate of bariatric
      surgery in underserved Medicare patients compared with underserved patients with
      other payers. RESULTS: The percentage of procedures performed at Centers of
      Excellence increased from 60.5% in 2008 to 73.1% in 2011 (p < 0.01). The
      proportion of Medicare patients receiving surgery at a Center of Excellence
      increased from 77.7% in 2008 to 88.1% in 2011 (p < 0.01). The proportion of
      bariatric surgery patients from underserved groups increased over time except
      among those residing in rural areas, for whom there was no change. Among patients
      from underserved populations, only black Medicare patients experienced an
      increase in bariatric surgery use when compared with non-Medicare patients. The
      travel distance for Medicare patients consistently exceeded travel distance for
      non-Medicare patients. However, travel distance for Medicare patients decreased
      slightly during the study period. CONCLUSIONS: Despite the longer travel distance
      required for Medicare patients, centralization of bariatric surgery to Centers of
      Excellence did not result in impaired access to care. In fact, in this study, an
      improvement in access to bariatric surgery was seen and persisted among some
      underserved populations.

PMID- 26304184
TI  - Impact of Intraoperative Pancreatoscopy with Intraductal Biopsies on Surgical
      Management of Intraductal Papillary Mucinous Neoplasm of the Pancreas.
AB  - BACKGROUND: Because of its known malignant potential, precise histologic
      diagnosis of intraductal papillary mucinous neoplasm of the pancreas (IPMN)
      during intraoperative pancreatoscopy (IOP) is essential for complete surgical
      resection. The impact of IOP on perioperative IPMN patient management was
      reviewed over 20 years of practice at Cliniques universitaires Saint-Luc,
      Brussels, Belgium. STUDY DESIGN: Among 86 IPMN patients treated by pancreatectomy
      between 1991 and 2013, 21 patients had a dilated main pancreatic duct enabling
      IOP and were retrospectively reviewed. The IOP was performed using an ultrathin
      flexible endoscope and biopsy forceps, and specimens of all suspicious lesions
      underwent frozen section examination. RESULTS: Complete IOP with intraductal
      biopsies was easily and safely performed in 21 patients, revealing 8 occult IPMN
      lesions. In 5 cases (23.8%), initially planned surgical resection was modified
      secondary to IOP: 3 for carcinoma in situ and 2 for invasive carcinoma. The
      postoperative morbidity rate at 3 months was 25.0% (5 of 20); 1 patient died from
      septic shock postoperatively and was excluded. Median follow-up was 93 months
      (range 13 to 248 months). Nineteen of 21 patients were still alive and free of
      disease at last follow-up (90.5%); there was 1 patient with invasive carcinoma at
      initial pathology (pT3 N1) who died of pulmonary recurrence 21 months after
      surgery. CONCLUSIONS: Intraoperative pancreatoscopy of the main pancreatic duct
      combined with intraductal biopsies plays a significant role in the surgical
      management of IPMN patients and should be used in all patients presenting a
      sufficiently dilated main pancreatic duct.

PMID- 26304185
TI  - My Journey as a Surgeon-Scientist Ten Years after Receiving the Inaugural
      Jacobson Promising Investigator Award.
AB  - The First Joan L and Julius H Jacobson Promising Investigator Awardee, Michael T
      Longaker MD, FACS In 2005, the research committee of the American College of
      Surgeons was tasked with selecting the recipient of a newly established award,
      "The Joan L and Julius H Jacobson Promising Investigator Award." According to the
      Jacobsons, the $30,000 award funded by Dr Jacobson should be given at least once
      every 2 years to a surgeon investigator at "the tipping point," who can
      demonstrate that his/her research shows the promise of leading to a significant
      contribution to the practice of surgery and patient safety. Every year, the
      research committee receives many excellent nominations and has the difficult task
      of selecting 1 awardee. In 2005, the awardee was a young promising investigator,
      Michael T Longaker, MD, FACS. Ten years later, Dr Longaker, a prominent
      researcher in the field of "scar formation," presents his journey in research and
      the impact of the Jacobson award on his career. Dr Longaker is now a national and
      international figure in the field of wound healing, tissue regeneration, and stem
      cell research. Kamal MF Itani, MD, FACS and Gail Besner, MD, FACS, on behalf of
      the Research Committee of the American College of Surgeons.

PMID- 26304186
TI  - First molecular assessment of the African swine fever virus status of
      Ornithodoros ticks from Swaziland.
AB  - African swine fever (ASF) is an economically significant haemorrhagic disease of
      domestic pigs. It is caused by the African swine fever virus (ASFV), a
      deoxyribonucleic acid (DNA)arbovirus. Argasid ticks of the genus Ornithodoros,
      which are widely distributed throughout southern Africa, play a primary role in
      virus maintenance and spread within the endemic sylvatic cycle. The ASF status of
      Swaziland is unknown, but this land-locked country is surrounded by ASF-positive
      countries, has a burgeoning pig industry and sylvatic cycle hosts present within
      its borders. In this first assessment of ASF status, warthog burrows in seven
      nature reserves and game management areas in Swaziland were investigated for tick
      and virus presence. Tick infestation rates of between 33.3% - 88.8% were
      recovered for the four Ornithodoros-infested reserves. A total of 562 ticks were
      screened for virus genome presence using a duplex Polymerase Chain Reaction (PCR)
      that targets the C-terminal end of the p72 gene of the ASFV and confirms DNA
      integrity through amplification of the 16S rRNA tick host gene. All samples were
      negative for virus genome presence and positive for the tick genome target.
      Nucleotide sequencing of the latter confirmed that Ornithodoros ticks from
      Swaziland are identical to those from the Kruger National Park in South Africa
      across the gene region characterised. Whilst this first evaluation of ASF
      presence in Swaziland indicates that the virus does not appear to be present in
      the key virus vector, the presence of sylvatic cycle hosts, together with the
      country's proximity to ASF-affected countries calls for expanded investigations
      and regular monitoring of the ASF status of Swaziland. 

PMID- 26304189
TI  - First language attrition.
AB  - Speakers who live in an L2 environment for an extended period of time often
      experience change in the way in which they use their L1, a process referred to as
      L1 attrition. This article provides an overview of language attrition phenomena
      at various linguistic levels. However, attrition cannot be trivially or linearly
      related to factors such as the frequency of use of the L1. It is argued here that
      attrition phenomena are not the outcome of a change to the underlying linguistic
      system nor of access problems due to an increase in activation thresholds, but of
      cross-linguistic influence in online speech production. WIREs Cogn Sci 2013,
      4:117-123. doi: 10.1002/wcs.1218 For further resources related to this article,
      please visit the WIREs website. 

PMID- 26304187
TI  - Polarization enhanced wide-field imaging for evaluating dermal changes caused by
      non-ablative fractional laser treatment.
AB  - BACKGROUND AND OBJECTIVE: Laser non-ablative fractional treatment (NAFT) is an
      important part of armamentarium of modern dermatology. Recently, such treatments
      have become available in at-home setting due to advent of self-application NAFT
      devices. Safety and clinical efficacy of NAFT are well established in multiple
      studies. Less information is available on morphological and functional changes in
      tissue occurring as a result of NAFT. Polarization-enhanced multispectral wide
      field imaging device allows for in vivo real time visualization of dermal
      structures. The objective of this study is to use this imaging modality to
      monitor early effects of the home-use NAFT on collagen networks. MATERIALS AND
      METHODS: Eight subjects (skin types I-III) used a commercially available NAFT
      device (wavelength 1410 nm, energy per pulse up to 15 mJ) to treat peri-orbital
      wrinkles in standard recommended mode, that is daily, for a period of two weeks.
      In each session, subjects applied a pre-treatment gel to the peri-orbital areas
      and then used the device, delivering 8-10 applications to each side of the face
      without overlap. Subjects were asked to use the highest device setting. Cross
      polarized 440 nm wide-field images were acquired from peri-orbital areas before
      and two weeks after the onset of the treatment regimen. Wide-field images were
      normalized and thresholded to a level of 40% brightness to emphasize collagen
      structure. Collagen content was quantitatively determined from thresholded
      collagen images. Improvement in collagen content at two weeks of daily treatments
      was assessed. RESULTS: Eight subjects (age 24-53 years) completed the study.
      Cross-polarized 440 nm wide-field images clearly delineated collagen networks.
      Quantitative assessment of collagen images revealed statistically significant (P
      < 0.05) improvement of collagen content at a time point of two weeks. Seven out
      of eight subjects showed varying degree of improvement. The increase of collagen
      content in responders ranged from 1-26%, with the mean improvement of 11%.
      Subjects in their early 40s showed the best improvement in comparison to younger
      and older age groups. CONCLUSIONS: Polarization-enhanced multispectral wide-field
      reflectance imaging method is a suitable technique for noninvasive in vivo
      assessment of dermal structures. Post-treatment images, taken three days after
      the last treatment session, demonstrate that non-ablative fractional treatment
      resulted in increased dermal collagen content as measured by the polarization
      enhanced technique as early as two weeks post onset of the treatments. However,
      further studies with a larger number of subjects and longer treatment period are
      required to determine the optimal regimen and how long the results will last.

PMID- 26304188
TI  - Reduced z-axis technique for CT Pulmonary angiography in pregnancy--validation
      for practical use and dose reduction.
AB  - The aim of this study is to determine the feasibility of using reduced scan range
      CT pulmonary angiography technique in pregnancy for pulmonary embolism (PE) and
      to quantify resulting dose reduction. This was a retrospective study. Eighty-four
      CTPA exams performed on pregnant women during 2004-2012. The scans were modified
      to create reduced anatomic coverage scans extending from aortic arch to base of
      heart. These were separately evaluated by two radiologists for PE and non-PE
      abnormalities. The results were then compared by the third radiologist with
      original radiology report and scans. Radiation dose reduction was evaluated
      prospectively in 36 patients as part of a quality control project. Two patients
      had PE and were successfully identified on reduced z-axis scans. Thirty-two exams
      were normal; rest had 60 pertinent and 16 had incidental findings. There were
      four incidental findings which included three benign thyroid nodules and one
      benign small lung nodule which were missed. None of these affected clinical
      outcome or management. There was 71 % radiation dose reduction. No PE or any
      important diagnoses are missed using reduced z-axis CTPA in pregnancy. There is a
      substantial radiation dose reduction. Hence, this technique is highly recommended
      in pregnancy. 

PMID- 26304190
TI  - What eye movements can tell us about sentence comprehension.
AB  - Eye movement data have proven to be very useful for investigating human sentence
      processing. Eyetracking research has addressed a wide range of questions, such as
      recovery mechanisms following garden-pathing, the timing of processes driving
      comprehension, the role of anticipation and expectation in parsing, the role of
      semantic, pragmatic, and prosodic information, and so on. However, there are some
      limitations regarding the inferences that can be made on the basis of eye
      movements. One relates to the nontrivial interaction between parsing and the eye
      movement control system which complicates the interpretation of eye movement
      data. Detailed computational models that integrate parsing with eye movement
      control theories have the potential to unpack the complexity of eye movement data
      and can therefore aid in the interpretation of eye movements. Another limitation
      is the difficulty of capturing spatiotemporal patterns in eye movements using the
      traditional word-based eyetracking measures. Recent research has demonstrated the
      relevance of these patterns and has shown how they can be analyzed. In this
      review, we focus on reading, and present examples demonstrating how eye movement
      data reveal what events unfold when the parser runs into difficulty, and how the
      parsing system interacts with eye movement control. WIREs Cogn Sci 2013, 4:125
      134. doi: 10.1002/wcs.1209 For further resources related to this article, please
      visit the WIREs website. 

PMID- 26304191
TI  - The basal ganglia.
AB  - Through its connections with widespread cortical areas and with dopaminergic
      midbrain areas, the basal ganglia are well situated to integrate patterns of
      cortical input with the dopaminergic reward signal originating in the midbrain.
      In this review, we consider the functions of the basal ganglia in relation to its
      gross and cellular anatomy, and discuss how these mechanisms subserve the
      thresholding and selection of motor and cognitive processes. We also discuss how
      the dopaminergic reward signal enables flexible task learning through modulation
      of striatal plasticity, and how reinforcement learning models have been used to
      account for various aspects of basal ganglia activity. Specifically, we will
      discuss the important role of the basal ganglia in instrumental learning,
      cognitive control, sequence learning, and categorization tasks. Finally, we will
      discuss the neurobiological and cognitive characteristics of Parkinson's disease,
      Huntington's disease and addiction to illustrate the relationship between the
      basal ganglia and cognitive function. WIREs Cogn Sci 2013, 4:135-148. doi:
      10.1002/wcs.1217 For further resources related to this article, please visit the
      WIREs website. 

PMID- 26304192
TI  - Experimental methods in studying child language acquisition.
AB  - This article reviews the some of the most widely used methods used for studying
      children's language acquisition including (1) spontaneous/naturalistic, diary,
      parental report data, (2) production methods (elicited production,
      repetition/elicited imitation, syntactic priming/weird word order), (3)
      comprehension methods (act-out, pointing, intermodal preferential looking,
      looking while listening, conditioned head turn preference procedure, functional
      neuroimaging) and (4) judgment methods (grammaticality/acceptability judgments,
      yes-no/truth-value judgments). The review outlines the types of studies and age
      groups to which each method is most suited, as well as the advantage and
      disadvantages of each. We conclude by summarising the particular methodological
      considerations that apply to each paradigm and to experimental design more
      generally. These include (1) choosing an age-appropriate task that makes
      communicative sense (2) motivating children to co-operate, (3) choosing a between
      /within-subjects design, (4) the use of novel items (e.g., novel verbs), (5)
      fillers, (6) blocked, counterbalanced and random presentation, (7) the
      appropriate number of trials and participants, (8) drop-out rates (9) the
      importance of control conditions, (10) choosing a sensitive dependent measure
      (11) classification of responses, and (12) using an appropriate statistical test.
      WIREs Cogn Sci 2013, 4:149-168. doi: 10.1002/wcs.1215 For further resources
      related to this article, please visit the WIREs website. CONFLICT OF INTEREST:
      The authors declare no conflict of interest.

PMID- 26304193
TI  - Emotion and moral judgment.
AB  - Research in psychology and cognitive science has consistently demonstrated the
      importance of emotion in a wide range of everyday judgments, including moral
      judgment. Most current accounts of moral judgment hold that emotion plays an
      important role, but the nature and extent of this role are still debated. We
      outline three increasingly strong claims about the role of emotion in moral
      judgment and assess the evidence for each. According to the first and least
      controversial claim, emotions follow from moral judgments, such that witnessing
      immorality can lead to negative emotions and witnessing moral virtue can lead to
      positive ones. According to the second claim, emotions amplify moral judgments,
      for instance, by making immoral acts seem even more immoral. Finally, on the last
      claim, emotions can actually moralize nonmoral behaviors-that is, they give
      nonmoral acts a moral status. Although this claim seems to be the most intriguing
      one theoretically, empirical support for it is still very limited. In this
      review, we discuss research findings that are in line with each of these views,
      we highlight recurring themes across these three categories of evidence, and we
      identify some open questions and areas for future research. WIREs Cogn Sci 2013,
      4:169-178. doi: 10.1002/wcs.1216 For further resources related to this article,
      please visit the WIREs website. 

PMID- 26304194
TI  - Visual working memory.
AB  - Visual working memory (VWM), the system of storing, manipulating, and utilizing,
      visual information is fundamental to many cognitive acts. Exploring the
      limitations of this system is essential to understand the characteristics of
      higher-order cognition, since at a basic level, VWM is the interface through
      which we interact with our environment. Given its important function, this system
      has become a very active area of research in the recent years. Here, we examine
      current models of VWM, along with the proposed reasons for what limits its
      capacity. This is followed by a short description of recent neural findings that
      have helped constrain models of VWM. In closing, we focus on work exploring
      individual differences in working memory capacity, and what these findings reveal
      about the intimate relationship between VWM and attention. WIREs Cogn Sci 2013,
      4:179-190. doi: 10.1002/wcs.1219 For further resources related to this article,
      please visit the WIREs website. 

PMID- 26304195
TI  - Neurophonetics.
AB  - Neurophonetics aims at the elucidation of the brain mechanisms underlying speech
      communication in our species. Clinical observations in patients with speech
      impairments following cerebral disorders provided the initial vantage point of
      this research area and indicated distinct functional-neuroanatomic systems to
      support human speaking and listening. Subsequent approaches-considering speech
      production a motor skill-investigated vocal tract movements associated with
      spoken language by means of kinematic and electromyographic techniques-allowing,
      among other things, for the evaluation of computational models suggesting
      elementary phonological gestures or a mental syllabary as basic units of speech
      motor control. As concerns speech perception, the working characteristics of
      auditory processing were first investigated based upon psychoacoustic techniques
      such as dichotic listening and categorical perception designs. More recently,
      functional hemodynamic neuroimaging and electrophysiological methods opened the
      door to the delineation of multiple stages of central auditory processing related
      to signal detection, classification, sensory memory processes, and, finally,
      lexical access. Beyond the control mechanisms in a stricter sense, both speech
      articulation and auditory processing represent examples of 'grounded cognition'.
      For example, both domains cannot be restricted to text-to-speech translation
      processes, but are intimately interwoven with neuropsychological aspects of
      speech prosody, including the vocal expression of affects and the actual
      performance of speech acts, transforming propositional messages to 'real'
      utterances. Furthermore, during language acquisition, the periphery of language
      i.e., hearing and speaking behavior-plays a dominant role for the construction of
      a language-specific mental lexicon as well as language-specific action plans for
      the production of a speech message. WIREs Cogn Sci 2013, 4:191-200. doi:
      10.1002/wcs.1211 For further resources related to this article, please visit the
      WIREs website. 

PMID- 26304196
TI  - What sign language creation teaches us about language.
AB  - How do languages emerge? What are the necessary ingredients and circumstances
      that permit new languages to form? Various researchers within the disciplines of
      primatology, anthropology, psychology, and linguistics have offered different
      answers to this question depending on their perspective. Language acquisition,
      language evolution, primate communication, and the study of spoken varieties of
      pidgin and creoles address these issues, but in this article we describe a
      relatively new and important area that contributes to our understanding of
      language creation and emergence. Three types of communication systems that use
      the hands and body to communicate will be the focus of this article: gesture,
      homesign systems, and sign languages. The focus of this article is to explain why
      mapping the path from gesture to homesign to sign language has become an
      important research topic for understanding language emergence, not only for the
      field of sign languages, but also for language in general. WIREs Cogn Sci 2013,
      4:201-211. doi: 10.1002/wcs.1212 For further resources related to this article,
      please visit the WIREs website. 

PMID- 26304197
TI  - Bridging across cognitive training and brain plasticity: a neurally inspired
      computational model of interactive skill learning.
AB  - This article reviews recent empirical and brain imaging data on effects of
      cognitive training methods on complex interactive skill learning, and presents a
      neurally inspired computational model that characterizes the effects of these
      training methods. In particular, the article focuses on research that shows that
      variable priority training (VPT), which requires learners to shift their
      priorities to different task components during training, often leads to better
      acquisition and retention of skills than fixed priority training (FPT). However,
      there is only weak evidence that shows that VPT can enhance transfer of complex
      interactive skills to untrained situations. Brain imaging studies show that VPT
      leads to significantly lower activations and a higher reduction of activities in
      attentional control areas after training than FPT. Research also shows that the
      volume of the striatum predicts the learning effects, but only in VPT. The
      computational model, developed based on learning mechanisms at the neural level,
      bridges across the empirical and the braining imaging results by explaining the
      effects of VPT and FPT at both the behavioral and neural levels. The results were
      discussed in the context of previous findings on cognitive training. WIREs Cogn
      Sci 2013, 4:225-236. doi: 10.1002/wcs.1214 For further resources related to this
      article, please visit the WIREs website. 

PMID- 26304199
TI  - [Antibioprophylaxy and multi drug resistant organism emergence].

PMID- 26304198
TI  - Structural basis of pathogen recognition by an integrated HMA domain in a plant
      NLR immune receptor.
AB  - Plants have evolved intracellular immune receptors to detect pathogen proteins
      known as effectors. How these immune receptors detect effectors remains poorly
      understood. Here we describe the structural basis for direct recognition of AVR
      Pik, an effector from the rice blast pathogen, by the rice intracellular NLR
      immune receptor Pik. AVR-PikD binds a dimer of the Pikp-1 HMA integrated domain
      with nanomolar affinity. The crystal structure of the Pikp-HMA/AVR-PikD complex
      enabled design of mutations to alter protein interaction in yeast and in vitro,
      and perturb effector-mediated response both in a rice cultivar containing Pikp
      and upon expression of AVR-PikD and Pikp in the model plant Nicotiana
      benthamiana. These data reveal the molecular details of a recognition event,
      mediated by a novel integrated domain in an NLR, which initiates a plant immune
      response and resistance to rice blast disease. Such studies underpin novel
      opportunities for engineering disease resistance to plant pathogens in staple
      food crops. 

PMID- 26304200
TI  - [Comparative study of the outcome of surgical management of vesico-vaginal
      fistulas with and without interposition of the Martius graft: A Cameroonian
      experience].
AB  - INTRODUCTION: This study aimed to investigate whether Martius' graft has an
      effect on the outcome of the surgical management of genitourinary fistula.
      PATIENTS AND METHODS: This was a retrospective comparative study of all cases of
      genitourinary fistula that underwent curative surgery in two Cameroonian
      hospitals. Patients were all operated between January 2005 and July 2011 in the
      gynecology unit of the Maroua Regional Hospital and the University Hospital
      Centre of Yaounde by a well-trained surgeon. The characteristics of women with
      fistulas operated without graft of Martius were compared with those of women
      operated with graft of Martius. RESULTS: Among the 81 genitourinary fistulas
      operated, 28 (34.6%) had benefited from graft of Martius. Depending on the
      characteristics of obstetric fistula, the two groups (that of patients who had a
      cure with, and that of patients who had a cure without interposition of graft of
      Martius) were similar: there was no difference in the proportion of rigid edges
      (89.3% vs. 73.6%, P=0.0989); in the proportion of vaginal flanges (78.6% vs.
      60.4%, P=0.0986), in the proportion of cervical localization (42.9% vs. 28.3%,
      P=0.3762), in the proportion of fistulas with a size greater than 2 cm (64.3% vs.
      39.6%, P=0.0702), nor in the proportion of recurrent fistulas (28.6% vs. 41.5%,
      P=0.2523) between the two groups. Similarly, both groups were comparable
      according to the results of surgery: there was no difference in the overall
      closure rate (85.7% vs. 79.2%, P=0.347) nor in the closure of fistula with
      continence (60.7% vs. 67.9%, P=0.260) between the two groups. The use of graft of
      Martius had no effect on the overall closure of genitourinary fistula in our
      series [OR: 1.57; 95% CI: 0.4 to 6.6; P=0.680]. CONCLUSION AND INTERPRETATION:
      The Martius graft does not seem to affect the outcome of the surgical management
      of genitourinary fistula. These results need to be confirmed by studies on a
      larger population.

PMID- 26304201
TI  - [Is publishing a part of a physician's job? Ethical considerations again].

PMID- 26304203
TI  - Stress and cognition.
AB  - Stress can affect cognition in many ways, with the outcome (i.e., facilitating or
      impairing) depending on a combination of factors related to both stress and the
      cognitive function under study. Among the factors identified as particularly
      relevant to define the cognitive effects of stress are the intensity or magnitude
      of stress, its origin (i.e., whether triggered by the task or externally), and
      its duration (i.e., whether acute or chronically delivered). At the cognitive
      end, the specific cognitive operation (e.g., implicit or explicit memory, long
      term or working memory, goal-directed or habit learning) and information
      processing phases (e.g., learning, consolidation, and retrieval) are essential as
      well to define stress effects. The emerging view is that mild stress tends to
      facilitate cognitive function, particularly in implicit memory or simple
      declarative tasks or when the cognitive load is not excessive. Exposure to high
      or very high stress acutely (whether elicited by the cognitive task or
      experienced before being trained or tested in the task) or chronically impairs
      the formation of explicit memories and, more generally, of those that require
      complex, flexible reasoning (as typically observed for hippocampus- and
      prefrontal cortex-related functions) while improving performance of implicit
      memory and well-rehearsed tasks (as reported for amygdala-dependent conditioning
      tasks and for striatum-related processes). In addition to these general
      principles, there are important individual differences in the cognitive impact of
      stress, with gender and age being particularly influencing factors. WIREs Cogn
      Sci 2013, 4:245-261. doi: 10.1002/wcs.1222 For further resources related to this
      article, please visit the WIREs website. 

PMID- 26304202
TI  - Phenotypic characterisation of RAB6A knockout mouse embryonic fibroblasts.
AB  - BACKGROUND INFORMATION: Rab6 is one of the most conserved Rab GTPaes throughout
      evolution and the most abundant Rab protein associated with the Golgi complex.
      The two ubiquitous Rab isoforms, Rab6A and Rab6A', that are generated by
      alternative splicing of the RAB6A gene, regulate several transport steps at the
      Golgi level, including retrograde transport between endosomes and Golgi,
      anterograde transport between Golgi and the plasma membrane, and intra-Golgi and
      Golgi to endoplasmic reticulum transport. RESULTS: We have generated mice with a
      conditional null allele of RAB6A. Mice homozygous for the RAB6A null allele died
      at an early stage of embryonic development. Mouse embryonic fibroblasts (MEFs)
      were isolated from RAB6A(loxP/loxP) Rosa26-CreERT2 and incubated with 4-hydroxy
      tamoxifen, resulting in the efficient depletion of Rab6A and Rab6A'. We show that
      Rab6 depletion affects cell growth, alters Golgi morphology and decreases the
      Golgi-associated levels of some known Rab6 effectors such as Bicaudal-D and
      myosin II. We also show that Rab6 depletion protects MEFs against ricin toxin and
      delays VSV-G secretion. CONCLUSIONS: Our study shows that RAB6 is an essential
      gene required for normal embryonic development. We confirm in MEF cells most of
      the functions previously attributed to the two ubiquitous Rab6 isoforms.

PMID- 26304204
TI  - Navigation and steering for autonomous virtual humans.
AB  - The ever-increasing applicability of interactive virtual worlds in industry and
      academia has given rise to the need for robust, versatile autonomous virtual
      humans to inject life into these environments. There are two fundamental problems
      that must be addressed to produce functional, purposeful autonomous populaces:
      (1)Navigation: finding a collision-free global path from an agent's start
      position to its target in large complex environments, and (2) Steering: moving an
      agent along the path while avoiding static and dynamic threats such as other
      agents. In this review, we survey the large body of contributions in steering and
      navigation for autonomous agents in dynamic virtual worlds. We describe the
      benefits and limitations of different proposed solutions and identify potential
      future research directions to meet the needs for the next generation of
      interactive virtual world applications. WIREs Cogn Sci 2013, 4:263-272. doi:
      10.1002/wcs.1223 For further resources related to this article, please visit the
      WIREs website. 

PMID- 26304205
TI  - Olfactory perception, cognition, and dysfunction in humans.
AB  - The main functions of olfaction relate to finding food, avoiding predators and
      disease, and social communication. Its role in detecting food has resulted in a
      unique dual mode sensory system. Environmental odorants are 'smelled' via the
      external nostrils, while volatile chemicals in food-detected by the same
      receptors-arrive via the nasopharynx, contributing to flavor. This arrangement
      allows the brain to link the consequences of eating with a food's odor, and then
      later to use this information in the search for food. Recognizing an odorant-a
      food, mate, or predator-requires the detection of complex chemical blends against
      a noisy chemical background. The brain solves this problem in two ways. First, by
      rapid adaptation to background odorants so that new odorants stand out. Second,
      by pattern matching the neural representation of an odorant to prior olfactory
      experiences. This account is consistent with olfactory sensory physiology,
      anatomy, and psychology. Odor perception, and its products, may be subject to
      further processing-olfactory cognition. While olfactory cognition has features in
      common with visual or auditory cognition, several aspects are unique, and even
      those that are common may be instantiated in different ways. These differences
      can be productively used to evaluate the generality of models of cognition and
      consciousness. Finally, the olfactory system can breakdown, and this may be
      predictive of the onset of neurodegenerative conditions such as Alzheimer's, as
      well as having prognostic value in other disorders such as schizophrenia. WIREs
      Cogn Sci 2013, 4:273-284. doi: 10.1002/wcs.1224 For further resources related to
      this article, please visit the WIREs website. 

PMID- 26304206
TI  - Semantics and pragmatics.
AB  - The fields of semantics and pragmatics are devoted to the study of
      conventionalized and context- or use-dependent aspects of natural language
      meaning, respectively. The complexity of human language as a semiotic system has
      led to considerable debate about how the semantics/pragmatics distinction should
      be drawn, if at all. This debate largely reflects contrasting views of meaning as
      a property of linguistic expressions versus something that speakers do. The fact
      that both views of meaning are essential to a complete understanding of language
      has led to a variety of efforts over the last 40 years to develop better
      integrated and more comprehensive theories of language use and interpretation.
      The most important advances have included the adaptation of propositional
      analyses of declarative sentences to interrogative, imperative and exclamative
      forms; the emergence of dynamic, game theoretic, and multi-dimensional theories
      of meaning; and the development of various techniques for incorporating context
      dependent aspects of content into representations of context-invariant content
      with the goal of handling phenomena such as vagueness resolution, metaphor, and
      metonymy. WIREs Cogn Sci 2013, 4:285-297. doi: 10.1002/wcs.1227 For further
      resources related to this article, please visit the WIREs website. CONFLICT OF
      INTEREST: The authors declare no conflict of interest.

PMID- 26304207
TI  - Learnability theory.
AB  - Learnability theory is a body of mathematical and computational results
      concerning questions such as: when is learning possible? What prior information
      is required to support learning? What computational or other resources are
      required for learning to be possible? It is therefore complementary both to the
      computational project of building machine learning systems and to the scientific
      project of understanding learning in people and animals through observation and
      experiment. Learnability theory includes work within a variety of theoretical
      frameworks, including, for example, identification in the limit, and Bayesian
      learning, which idealize learning in different ways. Learnability theory
      addresses one of the foundational questions in cognitive science: to what extent
      can knowledge be derived from experience? WIREs Cogn Sci 2013, 4:299-306. doi:
      10.1002/wcs.1228 For further resources related to this article, please visit the
      WIREs website. 

PMID- 26304208
TI  - Cognition in Down syndrome: a developmental cognitive neuroscience perspective.
AB  - Down syndrome (DS) is the most common genetic form of intellectual disability. DS
      results in a characteristic profile of cognitive and neurological dysfunction.
      The predominant theory of the pattern of neural deficits in this syndrome
      suggests that DS affects 'late-developing' neural systems, including the function
      of the prefrontal cortex and hippocampus. In order to evaluate the validity of
      this theory, in this review, I highlight data addressing the neurological and
      cognitive phenotype in DS across development. In particular, I address the
      evidence suggesting that DS may impact late-developing neural systems and end
      with the conclusion that some cognitive difficulties in DS must result from poor
      communication between late-developing regions. Analogous to recent theories of
      cognitive processing in autism, cognitive deficits in DS may be substantially
      impacted by less efficient interregional communication. Finally, I discuss some
      ways in which understanding the impact of altered neurodevelopment in DS has the
      potential to inform our understanding of species-typical trajectories of
      cognitive development. WIREs Cogn Sci 2013, 4:307-317. doi: 10.1002/wcs.1221 For
      further resources related to this article, please visit the WIREs website. 

PMID- 26304209
TI  - Embodied cognition.
AB  - Traditional views in philosophy of mind and cognitive science depict the mind as
      an information processor, one whose connections with the body and the world are
      of little theoretical importance. On the contrary, mounting empirical evidence
      shows that bodily states and modality-specific systems for perception and action
      underlie information processing, and that embodiment contributes to various
      aspects and effects of mental phenomena. This article will briefly review and
      discuss some of this evidence and what it implies. By challenging mainstream
      accounts of mind and cognition, embodiment views offer new ways of
      conceptualizing knowledge and suggest novel perspectives on cognitive variation
      and mind-body reductionism. WIREs Cogn Sci 2013, 4:319-325. doi: 10.1002/wcs.1226
      For further resources related to this article, please visit the WIREs website. 

PMID- 26304210
TI  - The true impact of the French pay-for-performance program on physicians'
      benzodiazepines prescription behavior.
AB  - OBJECTIVES: The French pay-for-performance (P4P) contract CAPI implemented by the
      national health insurance included a target-goal which aims at reducing
      benzodiazepines prescriptions. In this investigation, we would like to assess
      whether: (1) the general practitioners (GPs) having signed P4P contract obtain
      better results regarding the target-goal than non-signatories; (2) (part of) this
      progression is due to the CAPI contract itself (tentative measurement of a
      "causal effect"); (3) (part of) the money spent on this P4P incentive can be self
      financed with the amount of pharmaceuticals saved. METHODS: We matched cross
      sectional and longitudinal data including 4622 French GPs from June 2011 to
      December 2012. A treatment effect model using instrumental variables was
      performed to take into account potential self-selection issue in signing. After
      having identified the NET impact of the P4P, we calculate the cost of an avoided
      benzodiazepines treatment. RESULTS: In our study, GPs who have signed the CAPI
      contract (36 % of the sample) are more numerous in achieving benzodiazepines
      target goal than non-signatories: 90.7 vs. 85.5 %. After controlling for the self
      selection bias, the propensity of GPs to achieve the benzodiazepines target is
      only 0.31 % higher for signatories than for their non-signing counterparts
      estimate for June 2012, which yields a statistically significant gap. Our
      economic analysis demonstrates that the CAPI contract does not allow savings, but
      presents in 2012 a NET cost of 93.6? per avoided benzodiazepines treatment (291?
      in 2011). CONCLUSIONS: The P4P contract has a positive but modest impact on the
      achievement of GPs regarding benzodiazepines indicator.

PMID- 26304211
TI  - The use of non-speech oral-motor exercises among Indian speech-language
      pathologists to treat speech disorders: An online survey.
AB  - OBJECTIVE: Previous surveys in the United States of America (USA), the United
      Kingdom (UK), and Canada have indicated that most of the speech-language
      pathologists (SLPs) tend to use non-speech oral-motor exercises (NSOMEs) on a
      regular basis to treat speech disorders.At present, there is considerable debate
      regarding the clinical effectiveness of NSOMEs. The current study aimed to
      investigate the pattern and extent of usage of NSOMEs among Indian SLPs. METHOD:
      An online survey intended to elicit information regarding the use of NSOMEs was
      sent to 505 members of the Indian Speech and Hearing Association. The
      questionnaire consisted of three sections. The first section solicited
      demographic information, the second and third sections solicited information from
      participants who did and did not prefer to use NSOMEs, respectively. Descriptive
      statistics were employed to analyse the responses that were clinically relevant.
      RESULTS: A total of 127 participants responded to the survey. Ninety-one percent
      of the participants who responded to the survey indicated that they used NSOMEs.
      CONCLUSION: The results suggested that the percentage of SLPs preferring to use
      NSOMEsis similar to the findings of surveys conducted in the USA, the UK, and
      Canada. The Indian SLPs continue to use NSOMEs based on a multitude of beliefs.
      It is important for SLPs to incorporate the principles of evidence-based practice
      while using NSOMEs to provide high quality clinical care.

PMID- 26304212
TI  - The challenge of linguistic and cultural diversity: Does length of experience
      affect South African speech-language therapists' management of children with
      language impairment?
AB  - BACKGROUND: South African speech-language therapists (SLTs) currently do not
      reflect the country's linguistic and cultural diversity. The question arises as
      to who might be better equipped currently to provide services to multilingual
      populations: SLTs with more clinical experience in such contexts, or recently
      trained SLTs who are themselves linguistically and culturally diverse and whose
      training programmes deliberately focused on multilingualism and multiculturalism?
      AIMS: To investigate whether length of clinical experience influenced: number of
      bilingual children treated, languages spoken by these children, languages in
      which assessment and remediation can be offered, assessment instrument(s)
      favoured, and languages in which therapy material is required. METHOD: From
      questionnaires completed by 243 Health Professions Council of South Africa
      (HPCSA)-registered SLTs who treat children with language problems, two groups
      were drawn:71 more experienced (ME) respondents (20+ years of experience) and 79
      less experienced (LE) respondents (maximum 5 years of experience). RESULTS: The
      groups did not differ significantly with regard to (1) number of
      children(monolingual or bilingual) with language difficulties seen, (2) number of
      respondents seeing child clients who have Afrikaans or an African language as
      home language, (3) number of respondents who can offer intervention in Afrikaans
      or English and (4) number of respondents who reported needing therapy material in
      Afrikaans or English. However, significantly more ME than LE respondents reported
      seeing first language child speakers of English, whereas significantly more LE
      than ME respondents could provide services, and required therapy material, in
      African languages. CONCLUSION: More LE than ME SLTs could offer remediation in an
      African language, but there were few other significant differences between the
      two groups. There is still an absence of appropriate assessment and remediation
      material for Afrikaans and African languages, but the increased number of African
      language speakers entering the profession may contribute to better service
      delivery to the diverse South African population.

PMID- 26304213
TI  - Vocal effectiveness of speech-language pathology students: Before and after voice
      use during service delivery.
AB  - BACKGROUND: As a professional voice user, it is imperative that a speech-language
      pathologist's(SLP) vocal effectiveness remain consistent throughout the day. Many
      factors may contribute to reduced vocal effectiveness, including prolonged voice
      use, vocally abusive behaviours,poor vocal hygiene and environmental factors.
      OBJECTIVES: To determine the effect of service delivery on the perceptual and
      acoustic features of voice. METHOD: A quasi-experimental., pre-test-post-test
      research design was used. Participants included third- and final-year speech
      language pathology students at the University of Pretoria(South Africa). Voice
      parameters were evaluated in a pre-test measurement, after which the participants
      provided two consecutive hours of therapy. A post-test measurement was then
      completed. Data analysis consisted of an instrumental analysis in which the
      multidimensional voice programme (MDVP) and the voice range profile (VRP) were
      used to measure vocal parameters and then calculate the dysphonia severity index
      (DSI). The GRBASI scale was used to conduct a perceptual analysis of voice
      quality. Data were processed using descriptive statistics to determine change in
      each measured parameter after service delivery. RESULTS: A change of clinical
      significance was observed in the acoustic and perceptual parameters of voice.
      CONCLUSION: Guidelines for SLPs in order to maintain optimal vocal effectiveness
      were suggested.

PMID- 26304214
TI  - Translating tools for better parent-based assessment: An exploratory study.
AB  - BACKGROUND: Current speech language assessment and intervention measures are not
      always culturally valid, as they are not standardised specifically for the
      various cultural groups within the South African population; and thus need to be
      adapted. OBJECTIVES: The objective of this study was to examine the
      appropriateness and utility of translations of the Ages & Stages Questionnaire
      (ASQ) instrument (60 month age group) from English to the Hindi language and
      culture, which is represented in South Africa. METHODS: Biographical
      questionnaires, ASQ and evaluation thereof were translated in Hindi and completed
      by parents of 15 typically developing South African preschool children of Indian
      origin, at the 60 month age level (including children between 57 and 66 months).
      RESULTS: Participants reported that the questions were well phrased, and that
      illustrations and tips helped them to complete the questionnaires quickly and
      accurately. They preferred to be questioned in Hindi, which helped them
      understand the questions and made it easier to provide the necessary information
      to answer the questions. CONCLUSIONS: In conclusion, it is evident that this
      translation of the ASQ (60 month age group) from English to Hindi served as an
      appropriate tool for use with the middle socioeconomic class Hindi (Indian)
      language and culture. The results of this study would assist to determine the
      functionality of culturally and linguistically valid assessment tools for
      different populations, and would contribute to the development of Early Childhood
      Intervention as a whole in South Africa. It would also contribute to the
      development of multilingual informal school-readiness screening questionnaires
      appropriate for the South African context. This is particularly relevant, as
      school-readiness assessments take place at 60 months to ensure that the child is
      ready to learn by school age (6-7 years).[PDF to follow].

PMID- 26304215
TI  - Agrammatic aphasia verb and argument patterns in Kiswahili-English spontaneous
      language.
AB  - BACKGROUND: The spontaneous and narrative language of Kiswahili agrammatic
      aphasic and non-brain-damaged speakers was analysed. The bilingual participants
      were also tested in English to enable comparisons of verb production in the two
      languages. The significance of this study was to characterise bilingual Kiswahili
      English spontaneous agrammatic output. This was done by describing Kiswahili
      English bilingual output data with a specific focus on the production of verbs.
      The description involves comparison of verb and argument production in Kiswahili
      and English. METHODS AND PROCEDURES: The participants recruited for this study
      were drawn from two groups of participants (six non-fluent aphasic/agrammatic
      speakers and six non-brain-damaged). From each participant, a sample of
      spontaneous output was tape-recorded in English and Kiswahili based on the
      description and narration of the Flood rescue picture' and the 'Cookie theft
      picture'. The data elicited were compared for each subject and between the
      participants and relevant verb parameters have been analysed. The variables that
      were studied included mean length of utterance (MLU), inflectional errors, verb
      tokens and types, copulas and auxiliaries. Further, all verbs produced were
      classified as per their argument structure. RESULTS: The results from English
      data supported previous findings on agrammatic output. The agrammatic
      participants produced utterances with shorter MLU and simpler sentence structure.
      However, Kiswahili data surprisingly showed reversed results, with agrammatic
      speakers producing longer utterances than non-brain-damaged (NBD) controls. The
      results also revealed selective impairment in some agrammatic speakers who made
      inflectional errors. The verb argument structure showed contrasting results, with
      agrammatic speakers preferring transitive verbs whilst the NBD speakers used more
      intransitive verbs. CONCLUSIONS: The study attempts for the first time to
      characterise English-Kiswahili bilingual spontaneous and narrative output. A
      quantitative analysis of verb and argument production is conducted. The results
      of the English data are consistent with those in the literature; agrammatic
      speakers produce utterances with shorter MLU and simpler sentence structure.
      However, Kiswahili data reveals a surprisingly reversed pattern most notably with
      respect to MLU with agrammatics producing longer utterances than NBD controls.
      Argument structure analysis revealed that agrammatics used more transitive verbs
      than intransitives.

PMID- 26304216
TI  - Establishing a pharmacotherapy induced ototoxicity programme within a service
      learning approach.
AB  - Pharmacotherapy-induced ototoxicity is growing, especially in developing
      countries such as South Africa. This highlights the importance of ototoxicity
      monitoring and management of hearing loss. This article focuses on the
      establishment of an ototoxicity clinic as a site for the implementation of a
      service-learning module in the Audiology programme. The clinic offers a unique
      opportunity of collaboration between pharmacists and an audiologist where
      pharmacotherapy-induced ototoxicity is uniquely monitored. The Sefako Makgatho
      Health Sciences University (SMU) provides training to both the disciplines,
      audiology and pharmacy. The main aim of this article is to describe how
      ototoxicity monitoring is implemented in the curriculum within such an academic
      service-learning approach. Through service learning students develop a deeper
      understanding of course content, acquire new knowledge and engage in civic
      activity. It simultaneously provides a unique opportunity for interdisciplinary
      collaboration between the disciplines of audiology and pharmacy. The objectives
      for this programme are therefore to facilitate learning and to provide a service
      to the local community by identifying, preventing and monitoring medicine-induced
      hearing loss in in-hospital and out-patients; as well as to establish inter
      disciplinary collaboration between the disciplines and stakeholders for more
      effective service delivery. The constant interdisciplinary teamwork between the
      audiologist, pharmacist, physician and nursing staff in the wards results in best
      practice and management of patients with ototoxic damage.

PMID- 26304217
TI  - New graduates' perceptions of preparedness to provide speech-language therapy
      services in general and dysphagia services in particular.
AB  - BACKGROUND: Upon graduation, newly qualified speech-language therapists are
      expected to provide services independently. This study describes new graduates'
      perceptions of their preparedness to provide services across the scope of the
      profession and explores associations between perceptions of dysphagia theory and
      clinical learning curricula with preparedness for adult and paediatric dysphagia
      service delivery. METHODS: New graduates of six South African universities were
      recruited to participate in a survey by completing an electronic questionnaire
      exploring their perceptions of the dysphagia curricula and their preparedness to
      practise across the scope of the profession of speech-language therapy. RESULTS:
      Eighty graduates participated in the study yielding a response rate of 63.49%.
      Participants perceived themselves to be well prepared in some areas (e.g. child
      language: 100%; articulation and phonology: 97.26%), but less prepared in other
      areas (e.g. adult dysphagia: 50.70%; paediatric dysarthria: 46.58%; paediatric
      dysphagia: 38.36%) and most unprepared to provide services requiring sign
      language (23.61%) and African languages (20.55%). There was a significant
      relationship between perceptions of adequate theory and clinical learning
      opportunities with assessment and management of dysphagia and perceptions of
      preparedness to provide dysphagia services. CONCLUSION: There is a need for
      review of existing curricula and consideration of developing a standard speech
      language therapy curriculum across universities, particularly in service
      provision to a multilingual population, and in both the theory and clinical
      learning of the assessment and management of adult and paediatric dysphagia, to
      better equip graduates for practice.

PMID- 26304218
TI  - Comparison of the South African Spondaic and CID W-1 wordlists for measuring
      speech recognition threshold.
AB  - BACKGROUND: The home language of most audiologists in South Africa is either
      English or Afrikaans, whereas most South Africans speak an African language as
      their home language. The use of an English wordlist, the South African Spondaic
      (SAS) wordlist, which is familiar to the English Second Language (ESL)
      population, was developed by the author for testing the speech recognition
      threshold (SRT) of ESL speakers. OBJECTIVES: The aim of this study was to compare
      the pure-tone average (PTA)/SRT correlation results of ESL participants when
      using the SAS wordlist (list A) and the CID W-1 spondaic wordlist (list B - less
      familiar; list C - more familiar CID W-1 words). METHOD: A mixed-group
      correlational, quantitative design was adopted. PTA and SRT measurements were
      compared for lists A, B and C for 101 (197 ears) ESL participants with normal
      hearing or a minimal hearing loss (<26 dBHL; mean age 33.3). RESULTS: The Pearson
      correlation analysis revealed a strong PTA/SRT correlation when using list A
      (right 0.65; left 0.58) and list C (right 0.63; left 0.56). The use of list B
      revealed weak correlations (right 0.30; left 0.32). Paired sample t-tests
      indicated a statistically significantly stronger PTA/SRT correlation when list A
      was used, rather than list B or list C, at a 95% level of confidence.
      CONCLUSIONS: The use of the SAS wordlist yielded a stronger PTA/SRT correlation
      than the use of the CID W-1 wordlist, when performing SRT testing on South
      African ESL speakers with normal hearing, or minimal hearing loss (<26 dBHL).

PMID- 26304219
TI  - What can speech production errors tell us about cross-linguistic processing in
      bilingual aphasia? Evidence from four English/Afrikaans bilingual individuals
      with aphasia.
AB  - INTRODUCTION: The aim of this study is contribute to clinical practice of
      bilinguals around the globe, as well as to add to our understanding of bilingual
      aphasia processing, by analysing confrontation naming data from four
      Afrikaans/English bilingual individuals with acquired aphasia due to a left
      hemisphere stroke. METHODS: This is a case series analysis of four
      Afrikaans/English bilingual aphasic individuals following a left cerebrovascular
      accident. Error analysis of confrontation naming data in both languages was
      performed. Research questions were directed toward the between language
      differences in lexical retrieval abilities, types of errors produced and degree
      of cognate overlap. RESULTS: Three of the four participants showed significantly
      higher naming accuracy in first acquired language (L1) relative to the second
      acquired language (L2) and the largest proportion of error type for those three
      participants in both L1 and L2 was omission. One of the four participants
      (linguistically balanced) showed no between language accuracy difference.
      Regarding cognate overlap, there was a trend for higher accuracy for higher
      cognate words (compared to low). DISCUSSION: This study showed that naming
      performance in these four individuals was reflective of their relative language
      proficiency and use patterns prior to their stroke. These findings are consistent
      with the hierarchical model, in normal bilingual speakers and with persons with
      bilingual aphasia.

PMID- 26304220
TI  - Single-cell transcriptomics and functional target validation of brown adipocytes
      show their complex roles in metabolic homeostasis.
AB  - Brown adipocytes (BAs) are specialized for adaptive thermogenesis and, upon
      sympathetic stimulation, activate mitochondrial uncoupling protein (UCP)-1 and
      oxidize fatty acids to generate heat. The capacity for brown adipose tissue (BAT)
      to protect against obesity and metabolic disease is recognized, yet information
      about which signals activate BA, besides beta3-adrenergic receptor stimulation,
      is limited. Using single-cell transcriptomics, we confirmed the presence of mRNAs
      encoding traditional BAT markers (i.e., UCP1, expressed in 100% of BAs Adrb3,
      expressed in <50% of BAs) in mouse and have shown single-cell variability (>1000
      fold) in their expression at both the mRNA and protein levels. We further
      identified mRNAs encoding novel markers, orphan GPCRs, and many receptors that
      bind the classic neurotransmitters, neuropeptides, chemokines, cytokines, and
      hormones. The transcriptome variability between BAs suggests a much larger range
      of responsiveness of BAT than previously recognized and that not all BAs function
      identically. We examined the in vivo functional expression of 12 selected
      receptors by microinjecting agonists into live mouse BAT and analyzing the
      metabolic response. In this manner, we expanded the number of known receptors on
      BAs at least 25-fold, while showing that the expression of classic BA markers is
      more complex and variable than previously thought.

PMID- 26304221
TI  - Exploiting chimeric human antibodies to characterize a protective epitope of
      Neisseria adhesin A, one of the Bexsero vaccine components.
AB  - Neisseria adhesin A (NadA) is one of the antigens of Bexsero, the recently
      licensed multicomponent vaccine against serogroup B Neisseria meningitidis
      (MenB). NadA belongs to the class of oligomeric coiled-coil adhesins and is able
      to mediate adhesion and invasion of human epithelial cells. As a vaccine antigen,
      NadA has been shown to induce high levels of bactericidal antibodies; however,
      the domains important for protective response are still unknown. In order to
      further investigate its immunogenic properties, we have characterized the murine
      IgG1 mAb (6E3) that was able to recognize the 2 main antigenic variants of NadA
      on the surface of MenB strains. The epitope targeted by mAb 6E3 was mapped by
      hydrogen-deuterium exchange mass spectrometry and shown to be located on the
      coiled-coil stalk region of NadA (aa 206-249). Although no serum bactericidal
      activity was observed for murine IgG1 mAb 6E3, functional activity was restored
      when using chimeric antibodies in which the variable regions of the murine mAb
      6E3 were fused to human IgG3 constant regions, thus confirming the protective
      nature of the mAb 6E3 epitope. The use of chimeric antibody molecules will enable
      future investigations of complement-mediated antibody functionality independently
      of the Fc-mediated differences in complement activation.

PMID- 26304223
TI  - Computational models of planning.
AB  - The selection of the action to do next is one of the central problems faced by
      autonomous agents. Natural and artificial systems address this problem in various
      ways: action responses can be hardwired, they can be learned, or they can be
      computed from a model of the situation, the actions, and the goals. Planning is
      the model-based approach to action selection and a fundamental ingredient of
      intelligent behavior in both humans and machines. Planning, however, is
      computationally hard as the consideration of all possible courses of action is
      not computationally feasible. The problem has been addressed by research in
      Artificial Intelligence that in recent years has uncovered simple but powerful
      computational principles that make planning feasible. The principles take the
      form of domain-independent methods for computing heuristics or appraisals that
      enable the effective generation of goal-directed behavior even over huge spaces.
      In this paper, we look at several planning models, at methods that have been
      shown to scale up to large problems, and at what these methods may suggest about
      the human mind. WIREs Cogn Sci 2013, 4:341-356. doi: 10.1002/wcs.1233 The authors
      have declared no conflicts of interest for this article. For further resources
      related to this article, please visit the WIREs website. 

PMID- 26304222
TI  - The toxic effects of indoor atmospheric fine particulate matter collected from
      allergic and non-allergic families in Wuhan on mouse peritoneal macrophages.
AB  - Recent studies have shown that fine particulate matter (PM2.5) is associated with
      multiple adverse health outcomes and PM2.5-induced oxidative stress is now
      commonly known as a proposed mechanism of PM2.5-mediated toxicity. However, the
      association between allergic symptoms in children and exposure to PM2.5 has not
      been fully elucidated, particularly the role of PM2.5 on the indoor environment
      involved in allergy or non-allergy is unknown. The aim of the present study was
      to explore whether indoor PM2.5 from the homes of children with allergic symptoms
      had more increased risks of allergy than that of healthy ones and then compare
      the toxicity and inflammatory response of them. In this study, indoor PM2.5 was
      collected from the homes of schoolchildren with allergic symptoms and those of
      healthy ones respectively, and components of PM2.5 were analyzed. PM2.5-mediated
      oxidative damage and inflammatory response were further evaluated in mouse
      peritoneal macrophages based on its effects on the levels of reactive oxygen
      species accumulation, lipid peroxidation, DNA damage or cytokine production. It
      seems that oxidative stress may contribute to PM2.5-induced toxicity, and PM2.5
      from the allergic indoor environment produced more serious toxic effects and an
      inflammatory response on mouse peritoneal macrophages than that from a non
      allergic indoor environment.

PMID- 26304224
TI  - Haptic perception.
AB  - Fueled by novel applications, interest in haptic perception is growing. This
      paper provides an overview of the state of the art of a number of important
      aspects of haptic perception. By means of touch we can not only perceive quite
      different material properties, such as roughness, compliance, friction, coldness
      and slipperiness, but we can also perceive spatial properties, such as shape,
      curvature, size and orientation. Moreover, the number of objects we have in our
      hand can be determined, either by counting or subitizing. All these aspects will
      be presented and discussed in this paper. Although our intuition tells us that
      touch provides us with veridical information about our environment, the existence
      of prominent haptic illusions will show otherwise. Knowledge about haptic
      perception is interesting from a fundamental viewpoint, but it also is of eminent
      importance in the technological development of haptic devices. At the end of this
      paper, a few recent applications will be presented. WIREs Cogn Sci 2013, 4:357
      374. DOI: 10.1002/wcs.1238 CONFLICT OF INTEREST: The authors have declared no
      conflicts of interest for this article. For further resources related to this
      article, please visit the WIREs website. 

PMID- 26304225
TI  - Imprinting.
AB  - Imprinting is a type of learning by which an animal restricts its social
      preferences to an object after exposure to that object. Filial imprinting occurs
      shortly after birth or hatching and sexual imprinting, around the onset of sexual
      maturity; both have sensitive periods. This review is concerned mainly with
      filial imprinting. Filial imprinting in the domestic chick is an effective
      experimental system for investigating mechanisms underlying learning and memory.
      Extensive evidence implicates a restricted part of the chick forebrain, the
      intermediate and medial mesopallium (IMM), as a memory store for visual
      imprinting. After imprinting to a visual stimulus, neuronal responsiveness in IMM
      is specifically biased toward the imprinting stimulus. Both this bias and the
      strength of imprinting measured behaviorally depend on uninterrupted sleep
      shortly after training. When learning-related changes in IMM are lateralized they
      occur predominantly or completely on the left side. Ablation experiments indicate
      that the left IMM is responsible for long-term storage of information about the
      imprinting stimulus; the right side is also a store but additionally is necessary
      for extra storage outside IMM, in a region necessary for flexible use of
      information acquired through imprinting. Auditory imprinting gives rise to
      biochemical, neuroanatomical, and electrophysiological changes in the medio
      rostral nidopallium/mesopallium, anterior to IMM. Auditory imprinting has not
      been shown to produce learning-related changes in IMM. Imprinting may be
      facilitated by predispositions. Similar predispositions for faces and biological
      motion occur in domestic chicks and human infants. WIREs Cogn Sci 2013, 4:375
      390. doi: 10.1002/wcs.1231 For further resources related to this article, please
      visit the WIREs website. 

PMID- 26304226
TI  - Theory of mind.
AB  - Theory of mind and its development has been a significantly important-and
      challenging-topic of research in cognitive science for three decades. This review
      summarizes our knowledge of when and how children come to understand their own
      and others' minds, including the developmental timetable, old and new measures,
      and foundational skills in infancy. We review recent research on theory-of-mind
      (ToM) and learning, that is, ways in which children's understanding of other
      minds informs how they learn about the world, as well as evidence for an
      important role of domain-general cognitive skills (executive function) in the
      development of ToM, and the neural networks that are most strongly implicated.
      Finally, we propose future directions for research in this vast and growing
      field. WIREs Cogn Sci 2013, 4:391-402. doi: 10.1002/wcs.1232 The authors have
      declared no conflicts of interest for this article. For further resources related
      to this article, please visit the WIREs website. 

PMID- 26304227
TI  - Visual search.
AB  - Visual search is the act of looking for a predefined target among other objects.
      This task has been widely used as an experimental paradigm to study visual
      attention, and because of its influence has also become a subject of research
      itself. When used as a paradigm, visual search studies address questions
      including the nature, function, and limits of preattentive processing and focused
      attention. As a subject of research, visual search studies address the role of
      memory in search, the procedures involved in search, and factors that affect
      search performance. In this article, we review major theories of visual search,
      the ways in which preattentive information is used to guide attentional
      allocation, the role of memory, and the processes and decisions involved in its
      successful completion. We conclude by summarizing the current state of knowledge
      about visual search and highlight some unresolved issues. WIREs Cogn Sci 2013,
      4:415-429. doi: 10.1002/wcs.1235 The authors have declared no conflicts of
      interest for this article. For further resources related to this article, please
      visit the WIREs website. 

PMID- 26304228
TI  - Cognition and art: the current interdisciplinary approach.
AB  - For decades discussions of cognition and art were anchored in psychological and
      perceptual theories alone and were focused primarily on pictorial art, but in
      recent years a major conceptual shift has altered the discussions. Now, insights,
      concepts, and findings from archaeology, anthropology, brain evolution, biology,
      genetics, neurology, and neuroscience together with psychology and perception are
      leading into deeper scholarly explorations of the topic than was done previously.
      The implication is that the relationship between cognition and art can be fully
      grasped only when scholarship from all these disciplines is included in the
      discussions. We now emphasize that the diverse art forms practiced ubiquitously
      in human societies have a communicative value with deep biological roots and that
      art is another expression of the symbolic cognition that is the hallmark of the
      human brain, but that early societal-type organization played a pivotal role in
      the enduring practice of art. Moreover, neurological evidence from artists with
      brain damage suggests that the communicative nature of art is neuronally damage
      resistant, much more so than language. Rather than placing pictorial art center
      stage, as was done previously, the current interdisciplinary approach includes
      all the arts, points to sociocultural triggers for art practice, to the
      demographic conditions that prevailed in art's early beginnings, and to the
      interplay of these evolutionarily adaptive factors with deep biological
      motivations in the artist. WIREs Cogn Sci 2013, 4:431-439. doi: 10.1002/wcs.1236
      The authors have declared no conflicts of interest for this article. For further
      resources related to this article, please visit the WIREs website. 

PMID- 26304229
TI  - Music perception and cognition: development, neural basis, and rehabilitative use
      of music.
AB  - Music is a highly versatile form of art and communication that has been an
      essential part of human society since its early days. Neuroimaging studies
      indicate that music is a powerful stimulus also for the human brain, engaging not
      just the auditory cortex but also a vast, bilateral network of temporal, frontal,
      parietal, cerebellar, and limbic brain areas that govern auditory perception,
      syntactic and semantic processing, attention and memory, emotion and mood
      control, and motor skills. Studies of amusia, a severe form of musical
      impairment, highlight the right temporal and frontal cortices as the core neural
      substrates for adequate perception and production of music. Many of the basic
      auditory and musical skills, such as pitch and timbre perception, start
      developing already in utero, and babies are born with a natural preference for
      music and singing. Music has many important roles and functions throughout life,
      ranging from emotional self-regulation, mood enhancement, and identity formation
      to promoting the development of verbal, motor, cognitive, and social skills and
      maintaining their healthy functioning in old age. Music is also used clinically
      as a part of treatment in many illnesses, which involve affective, attention,
      memory, communication, or motor deficits. Although more research is still needed,
      current evidence suggests that music-based rehabilitation can be effective in
      many developmental, psychiatric, and neurological disorders, such as autism,
      depression, schizophrenia, and stroke, as well as in many chronic somatic
      illnesses that cause pain and anxiety. WIREs Cogn Sci 2013, 4:441-451. doi:
      10.1002/wcs.1237 The authors have declared no conflicts of interest for this
      article. For further resources related to this article, please visit the WIREs
      website. 

PMID- 26304231
TI  - Nursing Care: Care of the Perioperative Patient.
AB  - This article provides a general overview of nursing care principles including an
      approach to developing a nursing care plan using the nursing process as its
      foundation. The nursing process is a problem-solving approach used in planning
      patient care. This article also focuses on nursing care as it pertains to the
      respiratory, cardiovascular, and renal systems (fluid balance) as well as care of
      the recumbent patient. Knowledge of nursing care techniques and risk factors for
      complications puts the care provider in a position of being proactive rather than
      reactive to patient care needs. 

PMID- 26304233
TI  - Short-Term Effects of Blood Transfusions on Hepcidin in Preterm Infants.
AB  - BACKGROUND: Hepcidin, a key regulatory peptide hormone in iron homeostasis, may
      in future serve as a non-invasive iron status parameter for monitoring iron
      supplementation in preterm infants. For this, coexisting influencing factors
      should be taken into account. OBJECTIVES: To evaluate the short-term effects of
      red blood cell (RBC) transfusions on hepcidin concentrations in serum (HepS) and
      urine (HepU) of preterm infants. METHODS: This was a prospective, observational
      study conducted between May 2009 and September 2010 at a single neonatal unit
      (Tubingen University Hospital, Tubingen, Germany) in very preterm infants, i.e.
      with a gestational age (GA) of <32 weeks, who received clinically indicated RBC
      transfusions. The concentration of the mature, 25 amino-acid form of hepcidin was
      determined in serum und urine by competitive enzyme-linked immunosorbent assay
      together with cellular indices before and after transfusion. RESULTS: Twenty
      preterm infants born at a median GA of 26 + 0/7 (interquartile range: 24 + 6/7 to
      27 + 3/7) weeks received 27 RBC transfusions at a median corrected age of 31 +
      3/7 (29 + 6/7 to 34 + 5/7) weeks. When measured shortly after transfusion (mean
      time: 10 h), haematocrit values increased from a mean of 26.6% (SD 2.8) to 40.9%
      (SD 3.2); p < 0.0001. HepS also increased [geometric mean: 44.3 (95% confidence
      interval 30.8-63.8) ng/ml vs. 58.0 (35.7-94.3) ng/ml; p < 0.05] but HepU remained
      unaffected. CONCLUSION: The data indicate that HepS concentrations increase
      shortly after RBC transfusion in preterm infants. Long-term observational studies
      are needed to understand the dynamics of hepcidin regulation in preterm infants.

PMID- 26304232
TI  - Validation of a method for combining biplanar radiography and magnetic resonance
      imaging to estimate knee cartilage contact.
AB  - Combining accurate bone kinematics data from biplane radiography with cartilage
      models from magnetic resonance imaging, it is possible to estimate tibiofemoral
      cartilage contact area and centroid location. Proper validation of such
      estimates, however, has not been performed under loading conditions approximating
      functional tasks, such as gait, squatting, and stair descent. The goal of this
      study was to perform an in vitro validation to resolve the accuracy of cartilage
      contact estimations in comparison to a laser scanning gold standard. Results
      demonstrated acceptable reliability and accuracy for both contact area and
      centroid location estimates. Root mean square errors in contact area averaged
      8.4% and 4.4% of the medial and lateral compartmental areas, respectively.
      Modified Sorensen-Dice agreement scores of contact regions averaged 0.81 +/- 0.07
      for medial and 0.83 +/- 0.07 for lateral compartments. These validated methods
      have applications for in vivo assessment of a variety of patient populations and
      physical activities, and may lead to greater understanding of the relationships
      between knee cartilage function, effects of joint injury and treatment, and the
      development of osteoarthritis. 

PMID- 26304234
TI  - MiRNA-203 Reduces Nasopharyngeal Carcinoma Radioresistance by Targeting IL8/AKT
      Signaling.
AB  - Radioresistance poses a major challenge in nasopharyngeal carcinoma (NPC)
      treatment, but little is known about how miRNA (miR) regulates this phenomenon.
      In this study, we investigated the function and mechanism of miR-203 in NPC
      radioresistance, one of downregulated miRs in the radioresistant NPC cells
      identified by our previous microarray analysis. We observed that miR-203 was
      frequently downregulated in the radioresistant NPC tissues compared with
      radiosensitive NPC tissues, and its decrement significantly correlated with NPC
      radioresistance and poor patient survival, and was an independent predictor for
      reduced patient survival. In vitro radioresponse assays showed that miR-203 mimic
      markedly decreased NPC cell radioresistance. In a mouse model, therapeutic
      administration of miR-203 agomir dramatically sensitized NPC xenografts to
      irradiation. Mechanistically, we confirmed that IL8 was a direct target of miR
      203, and found that reduced miR-203 promoted NPC cell radioresistance by
      activating IL8/AKT signaling. Moreover, the levels of IL8 and phospho-AKT were
      significantly increased in the radioresistant NPC tissues compared with
      radiosensitive NPC tissues, and negatively associated with miR-203 level. Our
      data demonstrate that miR-203 is a critical determinant of NPC radioresponse, and
      its decrement enhances NPC radioresistance through targeting IL8/AKT signaling,
      highlighting the therapeutic potential of the miR-203/IL8/AKT signaling axis in
      NPC radiosensitization.

PMID- 26304235
TI  - Targeting G-Quadruplex DNA Structures by EMICORON Has a Strong Antitumor Efficacy
      against Advanced Models of Human Colon Cancer.
AB  - We previously identified EMICORON as a novel G-quadruplex (G4) ligand showing
      high selectivity for G4 structures over the duplex DNA, causing telomere damage
      and inhibition of cell proliferation in transformed and tumor cells. Here, we
      evaluated the antitumoral effect of EMICORON on advanced models of human colon
      cancer that could adequately predict human clinical outcomes. Our results showed
      that EMICORON was well tolerated in mice, as no adverse effects were reported,
      and a low ratio of sensitivity across human and mouse bone marrow cells was
      observed, indicating a good potential for reaching similar blood levels in
      humans. Moreover, EMICORON showed a marked therapeutic efficacy, as it inhibited
      the growth of patient-derived xenografts (PDX) and orthotopic colon cancer and
      strongly reduced the dissemination of tumor cells to lymph nodes, intestine,
      stomach, and liver. Finally, activation of DNA damage and impairment of
      proliferation and angiogenesis are proved to be key determinants of EMICORON
      antitumoral activity. Altogether, our results, performed on advanced experimental
      models of human colon cancer that bridge the translational gap between
      preclinical and clinical studies, demonstrated that EMICORON had an unprecedented
      antitumor activity warranting further studies of EMICORON-based combination
      treatments.

PMID- 26304237
TI  - A Novel Eg5 Inhibitor (LY2523355) Causes Mitotic Arrest and Apoptosis in Cancer
      Cells and Shows Potent Antitumor Activity in Xenograft Tumor Models.
AB  - Intervention of cancer cell mitosis by antitubulin drugs is among the most
      effective cancer chemotherapies. However, antitubulin drugs have dose-limiting
      side effects due to important functions of microtubules in resting normal cells
      and are often rendered ineffective by rapid emergence of resistance. Antimitotic
      agents with different mechanisms of action and improved safety profiles are
      needed as new treatment options. Mitosis-specific kinesin Eg5 represents an
      attractive anticancer target for discovering such new antimitotic agents, because
      Eg5 is essential only in mitotic progression and has no roles in resting,
      nondividing cells. Here, we show that a novel selective Eg5 inhibitor, LY2523355,
      has broad target-mediated anticancer activity in vitro and in vivo. LY2523355
      arrests cancer cells at mitosis and causes rapid cell death that requires
      sustained spindle-assembly checkpoint (SAC) activation with a required threshold
      concentration. In vivo efficacy of LY2523355 is highly dose/schedule-dependent,
      achieving complete remission in a number of xenograft tumor models, including
      patient-derived xenograft (PDX) tumor models. We further establish that histone
      H3 phosphorylation of tumor and proliferating skin cells is a promising
      pharmacodynamic biomarker for in vivo anticancer activity of LY2523355.

PMID- 26304238
TI  - The impact of caffeine on connexin expression in the embryonic chick
      cardiomyocyte micromass culture system.
AB  - Cardiomyocytes are electrically coupled by gap junctions, defined as clusters of
      low-resistance multisubunit transmembrane channels composed of connexins (Cxs).
      The expression of Cx40, Cx43 and Cx45, which are present in cardiomyocytes, is
      known to be developmentally regulated. This study investigates the premise that
      alterations in gap junction proteins are one of the mechanisms by which
      teratogens may act. Specifically, those molecules known to be teratogenic in
      humans could cause their effects via disruption of cell-to-cell communication
      pathways, resulting in an inability to co-ordinate tissue development. Caffeine
      significantly inhibited contractile activity at concentrations above and
      including 1500 MUm (P < 0.05), while not affecting cell viability and total
      protein, in the embryonic chick cardiomyocyte micromass culture system. The
      effects of caffeine on key cardiac gap junction protein (Cx40, Cx43 and Cx45)
      expression were analysed using immunocytochemistry and in-cell Western blotting.
      The results indicated that caffeine altered the expression pattern of Cx40, Cx43
      and Cx45 at non-cytotoxic concentrations (>=2000 MUm), i.e., at concentrations
      that did not affect total cell protein and cell viability. In addition the
      effects of caffeine on cardiomyocyte formation and function (contractile activity
      score) were correlated with modulation of Cxs (Cx40, Cx43 and Cx45) expression,
      at above and including 2000 MUm caffeine concentrations (P < 0.05). These
      experiments provide evidence that embryonic chick cardiomyocyte micromass culture
      may be a useful in vitro method for mechanistic studies of perturbation of
      embryonic heart development. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 26304239
TI  - Apraxia.
AB  - The term apraxia refers to 'higher level' disorders of motor control. Apraxia
      differs from other motor symptoms of unilateral brain damage by the bilaterality
      of symptoms following unilateral lesions. Lesions causing apraxia are located
      predominantly in the left hemisphere and apraxia is frequently, although not
      invariably, associated with aphasia. Examination for apraxia traditionally
      assesses imitation of gestures, performance of communicative gestures on command,
      and use of tools and objects. It has, however, been amply demonstrated that these
      three domains can be affected more or less independently from each other. This
      review discusses current topics of research and controversy from each of these
      domains concentrating on questions that are relevant for determining the border
      between motor and cognitive mechanisms underlying apraxic errors. For imitation,
      the proposal of a direct link from perception to motor execution is confronted
      with the hypothesis that body part coding is interpolated between perception and
      motor replication of gestures. Discussion of communicative gestures concentrates
      on pantomime of tool use and argues that pantomime is not equivalent to
      reproduction of the motor programs of actual tool use but that pantomimes are
      created by selection and combination of distinctive features of the object and
      its use. For tool use the boundary between visuo-motor coordination and knowledge
      about tool use is addressed by discussion of the selection of grips for use or
      for transport of tools. WIREs Cogn Sci 2013, 4:453-462. doi: 10.1002/wcs.1241 For
      further resources related to this article, please visit the WIREs website.
      CONFLICT OF INTEREST: The author has declared no conflicts of interest for this
      article.

PMID- 26304236
TI  - Specific CP110 Phosphorylation Sites Mediate Anaphase Catastrophe after CDK2
      Inhibition: Evidence for Cooperation with USP33 Knockdown.
AB  - Chromosomal instability (CIN) is a hallmark of solid tumor biology and is
      implicated in carcinogenesis. Preferentially eliminating malignant cells by
      targeting CIN and aneuploidy is an attractive antineoplastic strategy. We
      previously reported that CDK2 antagonism causes lung cancer cells to undergo
      anaphase catastrophe and apoptosis through inhibition of phosphorylation of the
      centrosomal protein CP110. Cells with activating KRAS mutations were particularly
      sensitive to CDK2 inhibition due to downregulation of CP110 protein levels. This
      study investigated mechanisms of CDK2 antagonism that mediate anaphase
      catastrophe via changes in CP110 protein expression and how activated KRAS
      affects CP110 levels in lung cancers. Site-directed mutagenesis revealed
      candidate CDK phosphorylation sites of CP110 (residues Ser 170 and Thr 194)
      critical for conferring anaphase catastrophe by altering centrosome clustering in
      mitosis. Intriguingly, KRAS mutation can promote CP110 protein degradation by
      upregulating the ubiquitin ligase SCF(cyclinF), which targets CP110 protein for
      destabilization. Finally, CDK2 inhibitor response was enhanced when combined with
      knockdown of the deubiquitinase USP33 that in turn accelerates CP110 protein
      degradation. Thus, this study provides molecular pharmacologic insights into how
      CP110 expression regulates response to CDK2 inhibition. An improved understanding
      of in vitro antineoplastic mechanisms of combining CDK2 antagonism with induced
      CP110 repression provides a rationale for exploring clinical consequences of this
      strategy. Taken together, preclinical findings obtained from combining CDK2
      inhibition with USP33 repression have implications for treating patients with non
      small cell lung cancers.

PMID- 26304240
TI  - Situated cognition.
AB  - Following the cognitive revolution, when knowing and learning have come to be
      theorized in terms of representations stored and processed in the mind, empirical
      and theoretical developments in very different scholarly disciplines have led to
      the emergence of the situated cognition hypothesis, which consists of a set of
      interlocking theses: cognition is embodied, fundamentally social, distributed,
      enacted, and often works without representations. We trace the historical origins
      of this hypothesis and discuss the evidential support this hypothesis receives
      from empirical and modeling studies. We distinguish the question of where
      cognition is located from the question of what cognition is, because the
      confounding of the two questions leads to misunderstandings in the sometimes
      ardent debates concerning the situated cognition hypothesis. We conclude with
      recommendations for interdisciplinary approaches to the nature of cognition.
      WIREs Cogn Sci 2013, 4:463-478. doi: 10.1002/wcs.1242 For further resources
      related to this article, please visit the WIREs website. CONFLICT OF INTEREST:
      The authors have declared no conflicts of interest for this article.

PMID- 26304241
TI  - Cognitive development: changing views of cognitive change.
AB  - The aim of research in cognitive development is to understand the origins of
      human knowledge and to provide an account of cognitive change. Theorizing
      regarding these issues is rooted in the nativist-empiricist debate. This article
      traces changing views in that debate, from the beginnings of psychology, through
      the cognitive revolution, Piaget, and alternatives to Piaget, including nativism,
      Vygotskyan theory, and information-processing work. The last section presents
      current theorizing and outlines various modern versions of nativism,
      constructivism, and empiricism. WIREs Cogn Sci 2013, 4:479-491. doi:
      10.1002/wcs.1245 For further resources related to this article, please visit the
      WIREs website. CONFLICT OF INTEREST: The author has declared no conflicts of
      interest for this article.

PMID- 26304242
TI  - Cognitive ethology.
AB  - Cognitive Ethology, the field initiated by Donald R Griffin, was defined by him
      as the study of the mental experiences of animals as they behave in their natural
      environment in the course of their normal lives. It encompasses both the problems
      defined by Chalmers as the 'hard' problem of consciousness, phenomenological
      experience, and the 'easy' problems, the phenomena that appear to be explicable
      (someday) in terms of computational or neural mechanisms. Sources for evidence of
      consciousness and other mental experiences that Griffin suggested and are updated
      here include (1) possible neural correlates of consciousness, (2) versatility in
      meeting novel challenges, and (3) animal communication which he saw as a
      potential 'window' into their mental experiences. Also included is a very brief
      discussion of pertinent philosophical and conceptual issues; cross-species neural
      substrates underlying selected cognitive abilities; memory capacities especially
      as related to remembering the past and planning for the future; problem solving,
      tool use and strategic behavioral sequences such as those needed in anti-predator
      behaviors. The capacity for mirror self-recognition is examined as a means to
      investigate higher levels of consciousness. The evolutionary basis for morality
      is discussed. Throughout are noted the admonitions of von Uexkull to the
      scientist to attempt to understand the Umwelt of each animal. The evolutionary
      and ecological impacts and constraints on animal capacity and behavior are
      examined as possible. WIREs Cogn Sci 2013, 4:493-509. doi: 10.1002/wcs.1239 For
      further resources related to this article, please visit the WIREs website.
      CONFLICT OF INTEREST: The author has declared no conflicts of interest for this
      article.

PMID- 26304243
TI  - The development of nonadjacent dependency learning in natural and artificial
      languages.
AB  - Nonadjacent dependencies occur over one or more intervening units and require
      learners to track discontinuous sequential relationships. These discontinuous
      relationships are present at multiple levels in language (e.g., as seen in
      morphosyntactic dependencies and at the phonological level in vowel harmony).
      Experiments suggest that these dependencies are acquired using statistical
      learning mechanisms and that this learning is also affected by perceptual biases.
      Artificial and natural language studies have shown that infants are sensitive to
      these statistical regularities but there appear to be developmental constraints
      on learning. Developmental investigations have also examined how knowledge and
      processing of the intervening elements affect learning, and whether categories
      can be acquired using nonadjacent dependency information. WIREs Cogn Sci 2013,
      4:511-522. doi: 10.1002/wcs.1244 CONFLICT OF INTEREST: The authors have declared
      no conflicts of interest for this article. For further resources related to this
      article, please visit the WIREs website. 

PMID- 26304244
TI  - The neural correlates of temporal reward discounting.
AB  - Temporal reward discounting (TD) refers to the decrease in subjective value of a
      reward when the delay to that reward increases. In recent years, a growing number
      of studies on the neural correlates of temporal reward discounting have been
      conducted. This article focuses on functional magnetic resonance imaging (fMRI)
      studies on TD in humans. First, we describe the different types of tasks (also
      from behavioral studies) and the dependent variables. Subsequently, we discuss
      the evidence for three neurobiological models of TD: the dual-systems model, the
      single-system model and the self-control model. Further, studies in which
      nontraditional tasks (e.g., with nonmonetary rewards) were used to study TD are
      reviewed. Finally, we discuss the neural correlates of individual differences in
      discounting, and its development across the lifespan. We conclude that the
      evidence for each of the three neurobiological models of TD is mixed, in that all
      models receive (partial) support, and several studies provide support for
      multiple models. Because of large differences between studies in task design and
      analytical approach, it is difficult to draw a firm conclusion regarding which
      model provides the best explanation of the neural correlates of temporal
      discounting. We propose that some components of these models can complement each
      other, and future studies should test the predictions offered by different models
      against each other. Several future research directions are suggested, including
      studying the connectivity between brain regions in relation to discounting, and
      directly comparing the neural mechanisms involved in discounting of monetary and
      primary rewards. WIREs Cogn Sci 2013, 4:523-545. doi: 10.1002/wcs.1246 CONFLICT
      OF INTEREST: The authors have declared no conflicts of interest for this article.
      For further resources related to this article, please visit the WIREs website. 

PMID- 26304247
TI  - Journal performance report.

PMID- 26304245
TI  - Invertebrate learning and cognition: relating phenomena to neural substrate.
AB  - Diverse invertebrate species have been used for studies of learning and
      comparative cognition. Although we have gained invaluable information from this,
      in this study we argue that our approach to comparative learning research is
      rather deficient. Generally invertebrate learning research has focused mainly on
      arthropods, and most of that within the Hymenoptera and Diptera. Any true
      comparative analysis of the distribution of comparative cognitive abilities
      across phyla is hampered by this bias, and more fundamentally by a reporting bias
      toward positive results. To understand the limits of learning and cognition for a
      species, knowing what animals cannot do is at least as important as reporting
      what they can. Finally, much more effort needs to be focused on the
      neurobiological analysis of different types of learning to truly understand the
      differences and similarities of learning types. In this review, we first give a
      brief overview of the various forms of learning in invertebrates. We also suggest
      areas where further study is needed for a more comparative understanding of
      learning. Finally, using what is known of learning in honeybees and the well
      studied honeybee brain, we present a model of how various complex forms of
      learning may be accounted for with the same neural circuitry required for so
      called simple learning types. At the neurobiological level, different learning
      phenomena are unlikely to be independent, and without considering this it is very
      difficult to correctly interpret the phylogenetic distribution of learning and
      cognitive abilities. WIREs Cogn Sci 2013, 4:561-582. doi: 10.1002/wcs.1248 For
      further resources related to this article, please visit the WIREs website. 

PMID- 26304248
TI  - Images in emergency medicine. Man with history of multiple abscesses.
      Hidradenitis suppurativa with an enterocutaneous fistula.

PMID- 26304249
TI  - Probing the Utility of the Rectal Examination.

PMID- 26304250
TI  - Commentary.

PMID- 26304251
TI  - Procalcitonin: An Effective Screening Tool and Safe Therapeutic Decisionmaking
      Aid for Emergency Department Patients With Suspected Sepsis.

PMID- 26304252
TI  - Procalcitonin Is Not a Useful Biomarker of Sepsis.

PMID- 26304253
TI  - Clinical Policy: Use of Intravenous Tissue Plasminogen Activator for the
      Management of Acute Ischemic Stroke in the Emergency Department.

PMID- 26304254
TI  - Change of shift. Worn out by fatigue training.

PMID- 26304255
TI  - Annals of Emergency Medicine Journal Club. Move Over Morphine: Is Ketamine an
      Effective and Safe Alternative for Treating Acute Pain?: September 2015 Annals of
      Emergency Medicine Journal Club.

PMID- 26304256
TI  - Images in emergency medicine. Elderly woman presenting after a collapse. Massive
      pulmonary embolism.

PMID- 26304257
TI  - Confounders, Mediators, and Selection Bias.

PMID- 26304258
TI  - In reply.

PMID- 26304259
TI  - Social Outreach in the Emergency Department: Are We Doing Enough?

PMID- 26304260
TI  - The Diagnostic Accuracy of Bedside Ocular Ultrasonography for the Diagnosis of
      Retinal Detachment: A Systematic Review and Meta-analysis.

PMID- 26304261
TI  - Unintentional Pediatric Exposure to a Synthetic Cannabinoid (AB-PINACA) Resulting
      in Coma and Intubation.

PMID- 26304262
TI  - Are All Oscillators Created Equal? In vitro Performance Characteristics of Eight
      High-Frequency Oscillatory Ventilators.
AB  - BACKGROUND: The mode of waveform generation and circuit characteristics differ
      between high-frequency oscillators. It is unknown if this influences performance.
      OBJECTIVES: To describe the relationships between set and delivered pressure
      amplitude (x0394;P), and the interaction with frequency and endotracheal tube
      (ETT) diameter, in eight high-frequency oscillators. METHODS: Oscillators were
      evaluated using a 70-ml test lung at 1.0 and 2.0 ml/cm H2O compliance, with mean
      airway pressures (PAW) of 10 and 20 cm H2O, frequencies of 5, 10 and 15 Hz, and
      an ETT diameter of 2.5 and 3.5 mm. At each permutation of PAW, frequency and ETT,
      the set x0394;P was sequentially increased from 15 to 50 cm H2O, or from 20 to
      100% maximum amplitude (10% increments) depending on the oscillator design. The
      x0394;P at the ventilator (x0394;PVENT), airway opening (x0394;PAO) and within
      the test lung (x0394;PTRACH), and tidal volume (V(T)) at the airway opening were
      determined at each set x0394;P. RESULTS: In two oscillators the relationships
      between set and delivered x0394;P were non-linear, with a plateau in x0394;P
      thresholds noted at all frequencies (Drager Babylog 8000) or >=10 Hz (Drager
      VN500). In all other devices there was a linear relationship between x0394;PVENT,
      x0394;PAO and x0394;PTRACH (all r2 >0.93), with differing attenuation of the
      pressure wave. Delivered V(T) at the different settings tested varied between
      devices, with some unable to deliver V(T) >3 ml at 15 Hz, and others generating
      V(T)>20 ml at 5 Hz and a 1:1 inspiratory-to-expiratory time ratio. CONCLUSIONS:
      Clinicians should be aware that modern high-frequency oscillators exhibit
      important differences in the delivered x0394;P and V(T).

PMID- 26304263
TI  - Patient and provider priorities for self-reported domains of HIV clinical care.
AB  - We sought to understand how HIV-infected patients, their providers, and HIV care
      researchers prioritize self-reported domains of clinical care. Participants rank
      ordered two lists of domains. A modified Delphi process was used for providers
      and researchers. Approximately 25% of patients were interviewed to discuss
      rationale for rank order choices. List 1 included anger, anxiety, depression,
      fatigue, physical function, pain, and sleep disturbance. List 2 included alcohol
      abuse, cognitive function, HIV stigma, HIV and treatment symptoms, medication
      adherence, positive affect, sexual risk behavior, sexual function, social roles,
      spirituality/meaning of life, and substance abuse. Seventy-four providers, 80 HIV
      care researchers, and 66 patients participated. Patients ranked context-based
      domains, such as HIV stigma, more highly than providers, while health behaviors,
      such as drug or alcohol use, ranked lower. Patients described a need to address
      wider-context challenges such as HIV stigma in order to positively impact health
      behaviors. Divergent patient and provider priorities highlight the importance of
      incorporating views from all stakeholders and suggests the need for a care
      approach that more effectively addresses contextual barriers to adverse health
      behaviors. 

PMID- 26304265
TI  - How thought is mapped into words.
AB  - To English speakers, the distinctions between blue and green, cup and glass, or
      cut and break seem self-evident. The intuition is that these words label
      categories that have an existence independent of language, and language merely
      captures the pre-existing categories. But cross-linguistic work shows that the
      named distinctions are not nearly as self-evident as they may feel. There is
      diversity in how languages divide up domains including color, number, plants and
      animals, drinking vessels and household containers, body parts, spatial
      relations, locomotion, acts of cutting and breaking, acts of carrying and
      holding, and more. Still, studies documenting variability across languages also
      uncover striking commonalities. Such commonalities indicate that there are
      sources of constraint on the variation. Both the commonalities and divergences
      carry important lessons for Cognitive Science. They speak to the causal relations
      among language, thought, and culture; the possibility of cross-culturally shared
      aspects of perception and cognition; the methods needed for studying general
      purpose, nonlinguistic concepts; and how languages are learned. WIREs Cogn Sci
      2013, 4:583-597. doi: 10.1002/wcs.1251 CONFLICT OF INTEREST: The authors have
      declared no conflicts of interest for this article. For further resources related
      to this article, please visit the WIREs website. 

PMID- 26304264
TI  - Human ketosteroid receptors interact with hazardous phthalate plasticizers and
      their metabolites: an in silico study.
AB  - Phthalic acid esters or phthalates are ubiquitous environmental pollutants known
      for their adverse health effects in test animals and, of late, in humans. Thus,
      in this molecular docking study - using Glide (Schrodinger) - the molecular
      interactions of 31 ligands, including 12 diphthalates, their monophthalates and
      phthalic acid with selected human ketosteroid receptors, i.e., androgen (hAR),
      progesterone (hPR) and glucocorticoid (hGR) receptors were explored and their
      binding affinities were compared with that of corresponding natural steroids and
      a known endocrine disrupting xenobiotic, bisphenol A (BPA). Mostly, diphthalates
      and monophthalates showed the potential for antisteroidal activity by interacting
      with hAR, hPR and hGR. Of them, diphenyl phthalate showed the highest G score (
      7.70 kcal mol(-1) ) with hAR, and the crucial amino acid (aa) residues in the
      ligand binding domain (LBD) of this receptor involved in the molecular
      interactions were Phe 764, Leu 704, Asn 705 and Thr 877. The mono-iso-decyl
      phthalate showed the highest G score (-8.36) with the hPR, and the crucial aa
      residues in the LBD interactions were Arg 766 Gln 725 and Phe 778. The mono-iso
      decyl phthalate also showed more affinity (-8.44) towards hGR than the natural
      ligand, and the aa residues in the LBD interactions were Gln 570 and Met 604. In
      addition to these, some other phthalates established comparable interactions with
      certain aa residues located in the LBD of these receptors, which resulted in
      higher G scores. Contrastingly, BPA and some natural ligands tested in this study
      showed lower G scores with these receptors than certain phthalates reported
      herein, i.e., certain phthalates are more toxic than the proven toxic BPA.
      Copyright (c) 2015 John Wiley & Sons, Ltd. 

PMID- 26304266
TI  - Cognitive aspects of schizophrenia.
AB  - Cognitive impairments are a central feature of schizophrenia and are present in
      most, if not all, cases. There are multiple domains of impairment seen and the
      level of severity of impairment is considerable. Impairments can be detected
      prior to the onset of clinical symptoms and the course of impairments involves
      some subtle early worsening followed by stability in most cases. Cognitive
      impairments are associated with functional disability, particularly in domains of
      vocational functioning and independence of residence. Both pharmacological and
      cognitive remediation interventions have been employed for the treatment of these
      impairments, with greater progress to date being made in cognitive remediation
      interventions. While much is known about cognitive impairments, treatment efforts
      are still in an early stage of development. WIREs Cogn Sci 2013, 4:599-608. doi:
      10.1002/wcs.1253 CONFLICT OF INTEREST: Dr. Harvey has received consulting fees
      from Abbott Labs, Amgen, Boehringer Ingelheim, Genentech, Johnson and Johnson,
      Pharma Neuroboost, Roche Parma, Sunovion Pharma, and Takeda Pharma during the
      past year. For further resources related to this article, please visit the WIREs
      website. 

PMID- 26304267
TI  - The thalamus: gateway to the mind.
AB  - The thalamus of the brain is far more than the simple sensory relay it was long
      thought to be. From its location at the top of the brain stem it interacts
      directly with nearly every part of the brain. Its dense loops into and out of
      cortex render it functionally a seventh cortical layer. Moreover, it receives and
      sends connections to most subcortical areas as well. Of course it does function
      as a very sophisticated sensory relay and thus is of vital importance to
      perception. But also it functions critically in all mental operations, including
      attention, memory, and consciousness, likely in different ways for different
      processes, as indicated by the consequences of damage to its various nuclei as
      well as by invasive studies in nonhuman animals. It plays a critical role also in
      the arousal system of the brain, in emotion, in movement, and in coordinating
      cortical computations. Given these important functional roles, and the dearth of
      knowledge about the details of its nonsensory nuclei, it is an attractive target
      for intensive study in the future, particularly in regard to its role in healthy
      and impaired cognitive functioning. WIREs Cogn Sci 2013, 4:523-545. doi:
      10.1002/wcs.1256 CONFLICT OF INTEREST: The author has declared no conflicts of
      interest for this article. For further resources related to this article, please
      visit the WIREs website. 

PMID- 26304268
TI  - Age-related decline in divided-attention: from theoretical lab research to
      practical real-life situations.
AB  - The purpose of this advanced review is to provide readers with an up-to-date
      synopsis of age-related changes in divided-attention abilities. An
      interdisciplinary approach is taken, supplying readers with evidence from very
      structured laboratory studies and findings from more ecological research studies
      that target real-life divided-attention situations (i.e., walking and talking).
      The review goes beyond the reported age-related declines in divided-attention
      abilities and offers the reader an overview of current cognitive (dual-task)
      training findings which suggest that these declines can be diminished with
      training. The contents of this review and the future directions proposed
      demonstrate that divided-attention research and its recent application to aging
      and mobility has become a major and fast growing scientific field of
      investigation. WIREs Cogn Sci 2013, 4:623-640. doi: 10.1002/wcs.1252 CONFLICT OF
      INTEREST: The authors have declared no conflicts of interest for this article.
      For further resources related to this article, please visit the WIREs website. 

PMID- 26304269
TI  - Modularity and mental architecture.
AB  - Debates about the modularity of cognitive architecture have been ongoing for at
      least the past three decades, since the publication of Fodor's landmark book The
      Modularity of Mind. According to Fodor, modularity is essentially tied to
      informational encapsulation, and as such is only found in the relatively low
      level cognitive systems responsible for perception and language. According to
      Fodor's critics in the evolutionary psychology camp, modularity simply reflects
      the fine-grained functional specialization dictated by natural selection, and it
      characterizes virtually all aspects of cognitive architecture, including high
      level systems for judgment, decision making, and reasoning. Though both of these
      perspectives on modularity have garnered support, the current state of evidence
      and argument suggests that a broader skepticism about modularity may be
      warranted. WIREs Cogn Sci 2013, 4:641-649. doi: 10.1002/wcs.1255 CONFLICT OF
      INTEREST: The author has declared no conflicts of interest for this article. For
      further resources related to this article, please visit the WIREs website. 

PMID- 26304270
TI  - Aphasias and theories of linguistic representation: representing frequency,
      hierarchy, constructions, and sequential structure.
AB  - Error and preservation patterns in aphasic speech show that the brain makes use
      of the frequencies of words, constructions, and collocations, as well as category
      membership and hierarchical structure, during language processing. Frequency
      effects are evident along two quasi-independent axes: syntagmatic (the sequential
      context, e.g., deploying correct functors, categories, and utterance-level
      intonation) and paradigmatic (the choice at any given linguistic level, e.g.,
      selecting content words and modifying structures). Frequency along the
      syntagmatic axis is shown to play a role in errors involving idioms,
      constructions, and collocations that cross major phrasal boundaries. Along the
      paradigmatic axis, frequency affects errors involving lexical selection,
      competing functors and inflected forms (e.g., using plural where singular is
      required). An account of language representation and processing that encompasses
      frequency as well as categorization and structure is compatible with what we know
      about how the brain works: increased experience with a linguistic structure
      results in increased activation-and strengthening-of the neural networks involved
      in processing that structure. These claims are supported by the literature on
      experimental work in normal speakers. Parsimony, plus the unexamined assumption
      that mental representation is like a written record (entries either present or
      absent, structure displayable in two dimensions), has been a misleading guide to
      modeling language representation. The substantial redundancy in representations
      and processing that is introduced by incorporating both frequency-based and
      hierarchy-based information is in fact appropriate for the brain as a fast,
      reliable, massively parallel error-correcting network with very large storage
      capacity and gradient representation strength. WIREs Cogn Sci 2013, 4:651-663.
      doi: 10.1002/wcs.1257 CONFLICT OF INTEREST: The authors have declared no
      conflicts of interest for this article. For further resources related to this
      article, please visit the WIREs website. 

PMID- 26304271
TI  - Judgment: a cognitive processing perspective.
AB  - Historically, judgment research has been mainly concerned with identifying
      regularities in sensation (e.g., discriminability laws) and assessing judgment
      accuracy. More recently, the focus has shifted toward specifying the information
      processing mechanisms underlying judgment and modeling them, for example, as
      cognitive strategies. We contrast this strategy approach with previous prominent
      research programs on judgment and provide an overview of various process-level
      accounts that have been proposed in terms of computational models (e.g.,
      compensatory and noncompensatory cue-abstraction strategies, evidence
      accumulation, exemplar processing, and parallel constraint satisfaction).
      Importantly, empirical investigations show that the cognitive processes
      underlying judgment differ considerably as a function of the individual's
      cognitive capacity and characteristics of the task environment (e.g., information
      cost, cognitive capacity, cue inter-correlations, relationship between cues and
      the to-be-judged criterion). We argue that these systematic contingencies in
      strategy use can be understood as adaptive responses to costs in learning,
      information acquisition, and strategy execution. WIREs Cogn Sci 2013, 4:665-681.
      doi: 10.1002/wcs.1259 CONFLICT OF INTEREST: The authors have declared no
      conflicts of interest for this article For further resources related to this
      article, please visit the WIREs website. 

PMID- 26304272
TI  - Latent semantic analysis.
AB  - This article reviews latent semantic analysis (LSA), a theory of meaning as well
      as a method for extracting that meaning from passages of text, based on
      statistical computations over a collection of documents. LSA as a theory of
      meaning defines a latent semantic space where documents and individual words are
      represented as vectors. LSA as a computational technique uses linear algebra to
      extract dimensions that represent that space. This representation enables the
      computation of similarity among terms and documents, categorization of terms and
      documents, and summarization of large collections of documents using automated
      procedures that mimic the way humans perform similar cognitive tasks. We present
      some technical details, various illustrative examples, and discuss a number of
      applications from linguistics, psychology, cognitive science, education,
      information science, and analysis of textual data in general. WIREs Cogn Sci
      2013, 4:683-692. doi: 10.1002/wcs.1254 CONFLICT OF INTEREST: The author has
      declared no conflicts of interest for this article. For further resources related
      to this article, please visit the WIREs website. 

PMID- 26304273
TI  - ART, cognitive science, and technology transfer.
AB  - Three computational examples illustrate how cognitive science can introduce new
      approaches to the analysis of large datasets. The first example addresses the
      question: how can a neural system learning from one example at a time absorb
      information that is inconsistent but correct, as when a family pet is called Spot
      and dog and animal, while rejecting similar incorrect information, as when the
      same pet is called wolf? How does this system transform such scattered
      information into the knowledge that dogs are animals, but not conversely? The
      second example asks: how can a real-time system, initially trained with a few
      labeled examples and a limited feature set, continue to learn from experience
      when confronted with oceans of additional information, without eroding reliable
      early memories? How can such individual systems adapt to their unique application
      contexts? The third example asks: how can a neural system that has made an error
      refocus attention on environmental features that it had initially ignored? Three
      models that address these questions, each based on the distributed adaptive
      resonance theory (dART) neural network, are applied to a spatial testbed created
      from multimodal remotely sensed data. The article summarizes key design elements
      of ART models, and provides links to open-source code for each system and the
      testbed dataset. WIREs Cogn Sci 2013, 4:707-719. doi: 10.1002/wcs.1260 CONFLICT
      OF INTEREST: The author has declared no conflicts of interest for this article.
      For further resources related to this article, please visit the WIREs website. 

PMID- 26304275
TI  - Novel Uses of Extracorporeal Membrane Oxygenation in Adults.
AB  - Extracorporeal membrane oxygenation (ECMO) has been available for decades, with
      its use steadily expanding in the setting of advances in technology. The most
      common indications for venovenous and venoarterial ECMO remain severe hypoxemic
      respiratory failure and cardiogenic shock, respectively. Refinements in
      extracorporeal circuitry and cannulation strategies have led to novel indications
      for ECMO in cardiopulmonary failure, including pulmonary hypertension,
      extracorporeal cardiopulmonary resuscitation, and less severe forms of the acute
      respiratory distress syndrome. There is hope for the development of destination
      device therapy, which could have significant implications for acute and chronic
      management of severe respiratory and cardiac disease. 

PMID- 26304276
TI  - Novel Uses of Targeted Temperature Management.
AB  - Targeted temperature management has an established role in treating the post
      cardiac arrest syndrome after out-of-hospital cardiac arrest with an initial
      rhythm of ventricular tachycardia/ventricular fibrillation. There is less certain
      benefit if the initial rhythm is pulseless electrical activity/asystole or for in
      hospital cardiac arrest. Targeted temperature management may have a role as
      salvage modality for conditions causing intracranial hypertension, such as
      traumatic brain injury, hepatic encephalopathy, intracerebral hemorrhage, and
      acute stroke. There is variable evidence for its use early in these disorders to
      minimize secondary neurologic injury. 

PMID- 26304277
TI  - ICU Telemedicine Solutions.
AB  - During the last 15 years, critical care services provided via telemedicine have
      expanded to now be incorporated into the care of 13% of patients in intensive
      care units (ICUs) in the United States. A response to shortfalls in the
      availability of critical care-trained providers has evolved into integrated
      programs of ICU care with contributions to improved outcomes through proactive
      management, population oversight, and standardization of care processes. The most
      impactful characteristics of successful ICU telemedicine programs are now better
      understood with more than a decade of national experience and the accrued
      benefits to health care systems.

PMID- 26304278
TI  - Controversies and Misconceptions in Intensive Care Unit Nutrition.
AB  - The early initiation of enteral nutrition remains a fundamental component of the
      management of critically ill and injured patients in the intensive care unit.
      Trophic feeding is equivalent, if not superior, to full-dose feeding. Parenteral
      nutrition has no proved benefit over enteral nutrition, which is the preferred
      route of nutritional support in intensive care unit patients with a functional
      gastrointestinal tract. Continuous enteral and parental nutrition inhibits the
      release of important enterohormones. These changes are reversed with intermittent
      bolus feeding. Whey protein, which is high in leucine, has a greater effect on
      insulin release and protein synthesis than does a soy- or casein-based enteral
      formula. 

PMID- 26304279
TI  - Sleep Loss and Circadian Rhythm Disruption in the Intensive Care Unit.
AB  - Critical illness is associated with profound sleep disruption. Causality is
      diverse and includes physiologic, psychological, and environmental factors. There
      are limited pharmacologic interventions available to treat sleep disturbances in
      critical illness; however, multidisciplinary strategies that alter the intensive
      care unit (ICU) environment and cluster care delivery have shown promise in sleep
      and circadian promotion and delirium reduction. With the appropriate
      administrative support and involvement of diverse ICU stakeholders, effective
      strategies could be created, implemented, and maintained to improve sleep
      disruption in critically ill patients. 

PMID- 26304280
TI  - Barriers and Challenges to the Successful Implementation of an Intensive Care
      Unit Mobility Program: Understanding Systems and Human Factors in Search for
      Practical Solutions.
AB  - ICU-acquired weakness is a common problem and carries significant morbidity.
      Despite evidence that early mobility can mitigate this, implementation outside of
      the research setting is lagging. Understanding barriers at the systems as well as
      individual level is a crucial step in successful implementation of an ICU
      mobility program. This includes taking inventory of waste, overburden and
      inconsistencies in the work environment. Appreciating regulative, normative as
      well as cultural forces at work is critical. Finally, key personnel, which
      include organizational leaders, innovation champions and end users of the
      proposed change need to be accounted for at each step during program
      implementation. 

PMID- 26304281
TI  - Integration of Palliative Care Services in the Intensive Care Unit: A Roadmap for
      Overcoming Barriers.
AB  - Clinicians working in the intensive care unit (ICU) confront death and dying
      daily. ICU care can be inconsistent with a patient's values, preferences, and
      previously expressed goals of care. Current evidence promotes the integration of
      palliative care services within the ICU setting. Palliative care bridges the gap
      between comfort and cure, and these services are growing in the United States.
      This article discusses the benefits and barriers to integration of ICU and
      palliative care services, and a stepwise approach to implementation of palliative
      care services. Integration of palliative care services into ICU workflow is
      increasingly seen as essential to providing high-quality, comprehensive critical
      care. 

PMID- 26304282
TI  - Clinical Reasoning and Risk in the Intensive Care Unit.
AB  - Clinical reasoning in medicine describes the process whereby a clinician gathers,
      assimilates, and assesses information about a person and their illness to assign
      a diagnosis and institute therapy. Care of patients in the intensive care unit
      involves managing a substantial quantity of incomplete, novel, and rapidly
      changing data. A modified nine-step bayesian approach to clinical reasoning
      comports well with this complex environment and is useful for assisting and
      educating novice learners to apply clinical reasoning accurately and
      consistently. When combined with a sophisticated approach to risk-benefit
      analysis to modify the treatment threshold, it becomes a useful and insightful
      tool for clinicians and those working in medical education. 

PMID- 26304283
TI  - Adverse Event Reporting and Quality Improvement in the Intensive Care Unit.
AB  - Patients in the intensive care unit are at high risk for experiencing adverse
      events and errors. The high-acuity health care needs of these vulnerable patients
      expose them to numerous medications, procedures, and health care providers. The
      occurrence of adverse events is associated with detriments to patient outcomes
      including increased mortality. Adverse event reporting is the most commonly used
      event-detection tool, but it should also be complimented with other tools such as
      trigger tools, chart review, and direct observation. Although adverse event
      reporting is essential for continuous improvement processes and is associated
      with improvements in safety culture, it remains significantly underutilized. 

PMID- 26304284
TI  - Five Questions Critical Care Educators Should Ask About Simulation-Based Medical
      Education.
AB  - Simulation is now commonly used in health care education, and a growing body of
      evidence supports its positive impact on learning. However, simulation-based
      medical education (SBME) involves a range of modalities, instructional methods,
      and presentations associated with different advantages and limitations. This
      review aims at better understanding the nature of SBME, its theoretic and proven
      benefits, its delivery, and the challenges posed by SBME. Areas requiring further
      research and development are also discussed. 

PMID- 26304285
TI  - Recent Advances in the Management of the Acute Respiratory Distress Syndrome.
AB  - Advances in management of the acute respiratory distress syndrome (ARDS) include
      the use of volume and pressure-limited ventilation and a fluid conservative
      strategy. Despite the extensive study of positive end expiratory pressure,
      consensus regarding the best approach to its application is lacking. The use of
      neuromuscular blocking agents and prone positioning in the setting of refractory
      hypoxemia is supported by the outcomes of recent studies. Alternate modes of
      ventilation remain unproven. A focus on ARDS risk factor reduction and the
      development of tools predicting progression to ARDS have the potential to further
      reduce its incidence. 

PMID- 26304286
TI  - Critically Ill Patients with Interstitial Lung Disease.
AB  - Interstitial lung disease (ILD) is a clinical syndrome of various etiologies and
      histopathologic categorization that, when clinically significant, impair
      respiratory function. Patients with ILD may develop critical illness from
      respiratory failure, nonpulmonary organ failure, or after surgical procedures.
      Additionally, the intensivist must be adept at recognizing exacerbation
      syndromes, which can complicate the disease course of some forms of ILD. This
      article discusses mechanical ventilation, noninvasive mechanical ventilation,
      exacerbation syndromes, and surgical concerns for patients with ILD who are
      critically ill. 

PMID- 26304287
TI  - Management of Right Heart Failure in the Intensive Care Unit.
AB  - Right heart failure is a clinical syndrome of various causes that commonly
      involves failure of the right ventricle (RV). The hemodynamic hallmark of the
      syndrome is increasing central venous pressure and worsening cardiac output with
      a rising RV end-diastolic pressure. When dealing with RV failure, clinicians must
      assess and optimize the intravascular volume state, support RV contractility, and
      address any pathologic elevations of afterload so that systemic perfusion is
      preserved. Despite these measures, there may still be a need to offer rescue
      interventions to the failing RV in carefully selected patients. 

PMID- 26304288
TI  - Advances in Sepsis Research.
AB  - Recent research has identified promising targets for therapeutic interventions
      aimed at modulating the inflammatory response in sepsis. Herein, the authors
      describe mechanisms involved in the clearance of pathogen toxin from the
      circulation and potential interventions aimed at enhancing clearance mechanisms.
      The authors also describe advances in the understanding of the innate immune
      response as potential therapeutic targets. Finally, novel potential treatment
      strategies aimed at decreasing vascular leak are discussed. 

PMID- 26304290
TI  - Advances and Challenges in Critical Care Medicine.

PMID- 26304289
TI  - Management of Infections with Drug-Resistant Organisms in Critical Care: An
      Ongoing Battle.
AB  - Infections with multidrug-resistant organisms (MDROs) are common in critically
      ill patients and are challenging to manage appropriately. Strategies that can be
      used in the treatment of MDRO infections in the intensive care unit (ICU) include
      combination therapy, adjunctive aerosolized therapy, and optimization of
      pharmacokinetics with higher doses or extended-infusion therapy as appropriate.
      Rapid diagnostic tests could assist in improving timely appropriate antimicrobial
      therapy for MDRO infections in the ICU. 

PMID- 26304291
TI  - Carers' experiences of accessing and navigating mental health care for older
      people in a rural area in Australia.
AB  - OBJECTIVES: Mental health care for older people is primarily delivered in the
      community and is largely dependent on informal carers. Mental health policy
      encourages partnerships between carers and service providers to facilitate
      service access, coordination and positive experience of care. However, carers
      often lack information and support from services, with the potential for carer
      burden, and negative impacts on their own health and capacity to fulfil caring
      tasks. This paper explores rural carers' experiences of accessing care from a
      range of services for older people with mental health problems. METHOD: The
      Pathways Interview Schedule was used to facilitate 9 in-depth care journey
      interviews with 11 carers of older people with a mental health problem.
      Interviews explored their journeys to and through mental health, aged care,
      primary care and social care services. Framework analysis was used to explore
      carers' experiences and perceptions of care with a focus on access enablers and
      barriers. RESULTS: Carers had a significant role in navigating services and
      operationalising care for their relative. Enablers to accessing care included
      carer knowledge and workers actively involving carers in planning. Barriers
      included carer mental health literacy, consumer and carer readiness for services,
      and worker misinterpretation of confidentiality and privacy laws. CONCLUSION:
      Carers should be considered key partners in mental health care planning that
      crosses service sectors. For this to occur, changes are required at the worker
      level, including increased communication between mental health workers and
      carers, and the service level, involving training for staff in interpreting
      confidentiality and privacy policy.

PMID- 26304293
TI  - Research in culture and psychology: past lessons and future challenges.
AB  - Since the dawn of psychology as a science, conceptual and methodological
      questions have accompanied research at the intersection of culture and
      psychology. We review some of these questions using two dominant concepts
      independent versus interdependent social orientation and analytic versus holistic
      cognitive style. Studying the relationship between culture and psychology can be
      difficult due to sampling restrictions and response biases. Since these
      challenges have been mastered, a wealth of research has accumulated on how
      culture influences cognition, emotion, and the self. Building on this work, we
      outline a set of new challenges for culture and psychology. Such challenges
      include questions about conceptual clarity, within-cultural and subcultural
      variations (e.g., variations due to social class), differentiation and
      integration of processes at the group versus individual level of analysis,
      modeling of how cultural processes unfold over time, and integration of insights
      from etic and emic methodological approaches. We review emerging work addressing
      these challenges, proposing that future research on culture and psychology is
      more exciting than ever. WIREs Cogn Sci 2014, 5:1-14. doi: 10.1002/wcs.1267
      CONFLICT OF INTEREST: The authors have declared no conflicts of interest for this
      article. For further resources related to this article, please visit the WIREs
      website. 

PMID- 26304292
TI  - Review article: the histological assessment of disease activity in ulcerative
      colitis.
AB  - BACKGROUND: In patients with ulcerative colitis (UC), mucosal healing has emerged
      as a major therapeutic goal, and is usually assessed endoscopically. Histological
      healing does not correlate very well with endoscopic mucosal healing in UC and
      persistent histological inflammation might be a better predictor of future
      clinical relapse than the endoscopic appearance alone. AIM: To define how
      histological assessment of disease activity should be best done in UC. METHODS:
      Electronic (PubMed/Embase) and manual search. RESULTS: At least 18 histological
      indices to assess disease activity in UC have been described, though none are
      fully validated. However, histological assessment is increasingly used as a
      secondary endpoint in clinical trials in UC. After reviewing and discussing
      existing histological scoring systems for UC activity, we describe features of
      histological response and define three grades of activity: (i) histological
      healing - complete resolution of abnormalities; (ii) quiescent disease, - lack of
      mucosal neutrophils but chronic inflammation may remain; (iii) active disease -
      presence of neutrophils plus possible epithelial damage. It is recommended that
      two biopsies are taken from each colonic segment which should include always
      biopsy of the rectum and the most affected segments. There is to date no agreed
      preferable scoring system but the Geboes Index is the best validated (kappa for
      interobserver variation 0.59-0.70). CONCLUSION: Histological assessment of
      disease activity in UC is increasingly used, but needs to be carefully defined.

PMID- 26304294
TI  - Speaker perception.
AB  - While humans use their voice mainly for communicating information about the
      world, paralinguistic cues in the voice signal convey rich dynamic information
      about a speaker's arousal and emotional state, and extralinguistic cues reflect
      more stable speaker characteristics including identity, biological sex and social
      gender, socioeconomic or regional background, and age. Here we review the
      anatomical and physiological bases for individual differences in the human voice,
      before discussing how recent methodological progress in voice morphing and voice
      synthesis has promoted research on current theoretical issues, such as how voices
      are mentally represented in the human brain. Special attention is dedicated to
      the distinction between the recognition of familiar and unfamiliar speakers, in
      everyday situations or in the forensic context, and on the processes and
      representational changes that accompany the learning of new voices. We describe
      how specific impairments and individual differences in voice perception could
      relate to specific brain correlates. Finally, we consider that voices are
      produced by speakers who are often visible during communication, and review
      recent evidence that shows how speaker perception involves dynamic face-voice
      integration. The representation of para- and extralinguistic vocal information
      plays a major role in person perception and social communication, could be
      neuronally encoded in a prototype-referenced manner, and is subject to flexible
      adaptive recalibration as a result of specific perceptual experience. WIREs Cogn
      Sci 2014, 5:15-25. doi: 10.1002/wcs.1261 CONFLICT OF INTEREST: The authors have
      declared no conflicts of interest for this article. For further resources related
      to this article, please visit the WIREs website. 

PMID- 26304295
TI  - Rationality.
AB  - A theory of rationality is a theory that evaluates instances of reasoning as
      rational, irrational, or (ir)rational to some degree. Theories can be categorized
      as rule-based or consequentialist. Rule-based theories say that rational
      reasoning accords with certain rules (e.g., of logic or probability).
      Consequentialist theories say that rational reasoning tends to produce good
      consequences. For instance, the reliabilist takes rationality to be reasoning
      that tends to produce mostly true beliefs. The pragmatist takes it to be
      reasoning that tends to produce mostly useful beliefs. This article reviews some
      of the features and the challenges of rule-based, reliabilist, and pragmatist
      theories of rationality. WIREs Cogn Sci 2014, 5:27-37. doi: 10.1002/wcs.1263
      CONFLICT OF INTEREST: The authors have declared no conflicts of interest for this
      article. For further resources related to this article, please visit the WIREs
      website. 

PMID- 26304296
TI  - Strategy selection: An introduction to the modeling challenge.
AB  - Modeling the mechanisms that determine how humans and other agents choose among
      different behavioral and cognitive processes-be they strategies, routines,
      actions, or operators-represents a paramount theoretical stumbling block across
      disciplines, ranging from the cognitive and decision sciences to economics,
      biology, and machine learning. By using the cognitive and decision sciences as a
      case study, we provide an introduction to what is also known as the strategy
      selection problem. First, we explain why many researchers assume humans and other
      animals to come equipped with a repertoire of behavioral and cognitive processes.
      Second, we expose three descriptive, predictive, and prescriptive challenges that
      are common to all disciplines which aim to model the choice among these
      processes. Third, we give an overview of different approaches to strategy
      selection. These include cost-benefit, ecological, learning, memory, unified,
      connectionist, sequential sampling, and maximization approaches. We conclude by
      pointing to opportunities for future research and by stressing that the selection
      problem is far from being resolved. WIREs Cogn Sci 2014, 5:39-59. doi:
      10.1002/wcs.1265 For further resources related to this article, please visit the
      WIREs website. 

PMID- 26304297
TI  - Visual category learning.
AB  - Visual categories group together different objects as the same kinds of thing. We
      review a selection of research on how visual categories are learned. We begin
      with a guide to visual category learning experiments, describing a space of
      common manipulations of objects, categories, and methods used in the category
      learning literature. We open with a guide to these details in part because
      throughout our review we highlight how methodological details can sometimes loom
      large in theoretical discussions of visual category learning, how variations in
      methodological details can significantly affect our understanding of visual
      category learning, and how manipulations of methodological details can affect how
      visual categories are learned. We review a number of core theories of visual
      category learning, specifically those theories instantiated as computational
      models, highlighting just some of the experimental results that help distinguish
      between competing models. We examine behavioral and neural evidence for single
      versus multiple representational systems for visual category learning. We briefly
      discuss how visual category learning influences visual perception, describing
      empirical and brain imaging results that show how learning to categorize objects
      can influence how those objects are represented and perceived. We close with work
      that can potentially impact translation, describing recent experiments that
      explicitly manipulate key methodological details of category learning procedures
      with the goal of optimizing visual category learning. WIREs Cogn Sci 2014, 5:75
      94. doi: 10.1002/wcs.1268 CONFLICT OF INTEREST: The authors have declared no
      conflicts of interest for this article. For further resources related to this
      article, please visit the WIREs website. 

PMID- 26304298
TI  - Cognitive enhancement.
AB  - Cognitive enhancement refers to the improvement of cognitive ability in normal
      healthy individuals. In this article, we focus on the use of pharmaceutical
      agents and brain stimulation for cognitive enhancement, reviewing the most common
      methods of pharmacologic and electronic cognitive enhancement, and the mechanisms
      by which they are believed to work, the effectiveness of these methods and their
      prevalence. We note the many gaps in our knowledge of these matters, including
      open questions about the size, reliability and nature of the enhancing effects,
      and we conclude with recommendations for further research. WIREs Cogn Sci 2014,
      5:95-103. doi: 10.1002/wcs.1250 CONFLICT OF INTEREST: The authors have declared
      no conflicts of interest for this article. For further resources related to this
      article, please visit the WIREs website. 

PMID- 26304299
TI  - The role of expectation in music: from the score to emotions and the brain.
AB  - Like discourse, music is a dynamic process that occurs over time. Listeners
      usually expect some events or structures of events to occur in the prolongation
      of a given context. Part of the musical emotional experience would depend upon
      how composers (improvisers) fulfill these expectancies. Musical expectations are
      a core phenomenon of music cognition, and the present article provides an
      overview of its foundation in the score as well as in listeners' behavior and
      brain, and how it can be simulated by artificial neural networks. We highlight
      parallels to language processing and include the attentional and emotional
      dimensions of musical expectations. Studying musical expectations is thus
      valuable not only for our understanding of music perception and production but
      also for more general brain functioning. Some open and challenging issues are
      summarized in this article. WIREs Cogn Sci 2014, 5:105-113. doi: 10.1002/wcs.1262
      CONFLICT OF INTEREST: The authors have no conflict of interest to declare. For
      further resources related to this article, please visit the WIREs website. 

PMID- 26304301
TI  - Caregiver and care recipient characteristics as predictors of psychotropic
      medication use in community-dwelling dementia patients.
AB  - OBJECTIVES: The current practice of prescribing psychotropic medication for the
      management of dementia-related behavioral disturbances is under substantial
      debate. Using Pearlin's stress process model as theoretical underpinning, the aim
      of this investigation is to identify caregiver and care recipient characteristics
      as predictors of anxiolytic, antipsychotic, and antidepressant use among
      community-dwelling dementia patients. We hypothesized that caregiving burden and
      patient characteristics, particularly behavior disturbances and pain, would be
      positively associated with psychotropic medication use. METHODS: Data for this
      exploratory, cross-sectional study were drawn from the baseline assessment of the
      Resources for Enhancing Alzheimer's Caregiver Health II trial. Only participants
      with full baseline information were examined (N = 598). Caregiver
      characteristics, such as confidence managing problematic behaviors, and care
      recipient characteristics including pain, problem behaviors, cognitive
      impairment, and functional impairment, were examined in relation to care
      recipient psychotropic medication use. RESULTS: Contrary to our hypothesis,
      behavioral disturbances and burden associated with these disturbances were not
      significantly associated with psychotropic use. Rather, caregiver characteristics
      such as race and overall vigilance, and care recipient characteristics such as
      cognitive status, functional status, and pain were significantly associated with
      the use of psychotropic medication. Findings differed by class of medication.
      CONCLUSION: These exploratory findings suggest the utility of a holistic approach
      to understanding the factors associated with pharmacotherapy among community
      dwelling elders with dementia. Significant associations between caregiver
      characteristics and care recipient psychotropic medication use suggest that
      educating caregivers in non-pharmacologic strategies hold promise for a more
      balanced biopsychosocial approach to maintaining dementia patients in the
      community.

PMID- 26304302
TI  - Systematic review: microbial dysbiosis and nonalcoholic fatty liver disease.
AB  - BACKGROUND: The human intestinal microbiota is a key regulator of host metabolic
      and immune functions and alterations in the microbiome ('dysbiosis') have been
      implicated in several human diseases. Because of the anatomical links between the
      intestines and the liver, dysbiosis may also disrupt hepatic function and thereby
      contribute to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). AIM:
      To perform a comprehensive review of the medical literature investigating
      associations between intestinal dysbiosis and NAFLD, with a particular emphasis
      on studies that characterise the microbiome in NAFLD. METHODS: We conducted a
      search of PubMed, Embase, and Web of Science using multiple search terms
      including: 'NAFLD, NASH, fatty liver, steatohepatitis' combined with 'metagenome,
      microbiom*, microbiota*, fecal flora, intestinal flora, gut bacteria'. Results
      were manually reviewed and studies selected based on relevance to intestinal
      microbiota and NAFLD. We also included studies that addressed potential
      mechanistic models of pathways linking the dysbiosis to NAFLD. RESULTS: Nine
      studies (five human and four animal models) were identified in our search that
      assessed associations between specific intestinal microbiota composition and
      NAFLD. We reviewed and summarised the results of additional investigations that
      more broadly addressed the mechanisms by which the microbiome may impact NAFLD
      pathogenesis. CONCLUSIONS: Investigations in humans and animals demonstrate
      associations between intestinal dysbiosis and NAFLD; however, causality has not
      been proven and mechanistic links require further delineation. As the field of
      microbiome research matures in techniques and study design, more detailed
      insights into NAFLD pathogenesis and its associations with the intestinal
      microbiota will be elucidated.

PMID- 26304303
TI  - The involvement of midwives' associations in policy and planning about the
      midwifery workforce: A global survey.
AB  - OBJECTIVE: a fit-for-purpose midwifery workforce is needed to respond to the
      current and future needs in sexual, reproductive, maternal and newborn health and
      to achieve universal health coverage. Evidence-based policy and planning that
      involves all stakeholders, including professional associations can assist with
      the development of such a workforce. The aim of the study was to explore how and
      when midwives' associations are involved in the planning processes for the
      midwifery workforce and which tools and approaches the associations perceived
      were used to support human resources for health policy. METHODS: all 108 member
      associations of the International Confederation of Midwives were invited to
      participate. A questionnaire collected data including: the involvement of the
      association in the national planning dialogue, processes and methods for
      participation and engagement; mechanisms to guide and inform decision-making;
      and, the tools, data and evidence used to influence human resources for health
      policy. A descriptive analysis was conducted and comparisons were made by country
      group based on national income strata. RESULTS: 73 (68%) midwives' associations
      participated in the study, representing 67 (71%) countries. In most (95%)
      countries, the planning process to determine the provision of reproductive,
      maternal and newborn health was centralised at the ministry of health level and
      included midwives' associations amongst others. Less than two thirds of
      associations reported involvement in planning and policy. The planning processes
      in which they took part were the reproductive, maternal and newborn plan (63%),
      the national health plan (58%), and the human resources for health plan (52%).
      Planning was more frequently undertaken at national than sub-national levels in
      middle- and low-income countries than in high-income countries. Midwives
      associations were often unaware of the human resources for health approaches used
      to calculate the number of midwives required, and reported low use of benchmarks,
      guidelines and supporting tools during their involvement in the planning process.
      CONCLUSION: although midwives associations were involved in planning and decision
      making processes for midwifery, their participation was often limited. These
      associations represent a key provider group in sexual, reproductive, maternal and
      newborn health and as such have a greater capacity to contribute to policy
      development and planning and have a meaningful contribution to the achievement of
      the goals of universal health coverage.

PMID- 26304304
TI  - Automated theorem proving.
AB  - Automated theorem proving is the use of computers to prove or disprove
      mathematical or logical statements. Such statements can express properties of
      hardware or software systems, or facts about the world that are relevant for
      applications such as natural language processing and planning. A brief
      introduction to propositional and first-order logic is given, along with some of
      the main methods of automated theorem proving in these logics. These methods of
      theorem proving include resolution, Davis and Putnam-style approaches, and
      others. Methods for handling the equality axioms are also presented. Methods of
      theorem proving in propositional logic are presented first, and then methods for
      first-order logic. WIREs Cogn Sci 2014, 5:115-128. doi: 10.1002/wcs.1269 CONFLICT
      OF INTEREST: The authors has declared no conflicts of interest for this article.
      For further resources related to this article, please visit the WIREs website. 

PMID- 26304305
TI  - Global disorders of consciousness.
AB  - In recent decades there has been a great deal of interest in global disorders of
      consciousness, such as the vegetative state, the minimally conscious state, and
      epileptic absence seizures. Global disorders of consciousness pose significant
      challenges to consciousness science in that the ordinary pretheoretical criteria
      for the ascription of consciousness are not easily applied in such contexts, and
      it is often unclear what kinds of conscious states-if any-patients are in. At the
      same time, global disorders of consciousness also promise to reveal a great deal
      about the nature of consciousness and the relationship between consciousness and
      cognitive and behavioral control. WIREs Cogn Sci 2014, 5:129-138. doi:
      10.1002/wcs.1270 CONFLICT OF INTEREST: The authors have declared no conflicts of
      interest for this article. For further resources related to this article, please
      visit the WIREs website. 

PMID- 26304306
TI  - Spatial language and abstract concepts.
AB  - What is the relationship between spatial language and abstract concepts? When
      people talk about abstract things that they can never see or touch, they often
      use spatial metaphors (e.g., a long vacation, a high price, a close friendship).
      According to theories of metaphorical mental representation, linguistic metaphors
      reflect underlying mental metaphors. Yet, behavioral experiments show that this
      is only one of the possible relationships between spatial metaphors in language
      and our spatial conceptualizations of abstract domains. In some cases, linguistic
      metaphors not only reflect speakers' thoughts, they also change those thoughts,
      such that people who use different linguistic metaphors rely on correspondingly
      different mental metaphors. Alternatively, spatial metaphors in language may
      reflect the way people conceptualize an abstract domain in some circumstances,
      but not in others. Finally, spatial language may reflect the way an abstract
      domain is typically conceptualized by some people, but not by others. There is no
      single relationship between spatial language and abstract concepts. Discovering
      whether (and under what conditions) a linguistic metaphor corresponds to a mental
      metaphor can illuminate the ways in which our interactions with the physical and
      social environment shape our mental lives. WIREs Cogn Sci 2014, 5:139-149. doi:
      10.1002/wcs.1271 CONFLICT OF INTEREST: The authors have declared no conflicts of
      interest for this article. For further resources related to this article, please
      visit the WIREs website. 

PMID- 26304307
TI  - The human nature of culture and education.
AB  - Human cultures educate children with different strategies. Ancient hunter
      gatherers 200,000 years ago, with bodies and brains like our own, in bands of a
      hundred well-known individuals or less, depended on spontaneous cooperative
      practice of knowledge and skills in a natural world. Before creating language,
      they appreciated beautiful objects and music. Anthropologists observe that
      similar living cultures accept that children learn in playful 'intent
      participation'. Large modern industrial states with millions of citizens
      competing in a global economy aim to instruct young people in scientific concepts
      and the rules of literacy and numeracy deemed important for employment with
      elaborate machines. Our psychobiological theories commonly assume that an infant
      starts with a body needing care and emotional regulation and a mind that
      assimilates concepts of objects by sensorimotor action and requires school
      instruction in rational principles after several years of cognitive development.
      Evidence from archeology and evolutionary anthropology indicates that Homo
      sapiens are born with an imaginative and convivial brain ready for the pleasure
      of shared invention and with a natural sense of beauty in handmade objects and
      music. In short, there are innate predispositions for culture for practicing
      meaningful habits and artful performances that are playfully inventive and
      seductive for companionship in traditions, and soon capable of grasping the
      clever purpose of shared tasks and tools. This knowledge of inventive human
      nature with esthetic and moral sensibilities has important implications for
      educational policy in our schools. WIREs Cogn Sci 2014, 5:173-192. doi:
      10.1002/wcs.1276 CONFLICT OF INTEREST: The authors have declared no conflicts of
      interest for this article. For further resources related to this article, please
      visit the WIREs website. 

PMID- 26304308
TI  - Game playing.
AB  - Game playing has been a core domain of artificial intelligence research since the
      beginnings of the field. Game playing provides clearly defined arenas within
      which computational approaches can be readily compared to human expertise through
      head-to-head competition and other benchmarks. Game playing research has
      identified several simple core algorithms that provide successful foundations,
      with development focused on the challenges of defeating human experts in specific
      games. Key developments include minimax search in chess, machine learning from
      self-play in backgammon, and Monte Carlo tree search in Go. These approaches have
      generalized successfully to additional games. While computers have surpassed
      human expertise in a wide variety of games, open challenges remain and research
      focuses on identifying and developing new successful algorithmic foundations.
      WIREs Cogn Sci 2014, 5:193-205. doi: 10.1002/wcs.1278 CONFLICT OF INTEREST: The
      author has declared no conflicts of interest for this article. For further
      resources related to this article, please visit the WIREs website. 

PMID- 26304309
TI  - Phantom limbs: pain, embodiment, and scientific advances in integrative
      therapies.
AB  - Research over the past two decades has begun to identify some of the key
      mechanisms underlying phantom limb pain and sensations; however, this continues
      to be a clinically challenging condition to manage. Treatment of phantom pain,
      like all chronic pain conditions, demands a holistic approach that takes into
      consideration peripheral, spinal, and central neuroplastic mechanisms. In this
      review, we focus on nonpharmacological treatments tailored to reverse the
      maladaptive neuroplasticity associated with phantom pain. Recent scientific
      advances emerging from interdisciplinary research between neuroscience, virtual
      reality, robotics, and prosthetics show the greatest promise for alternative
      embodiment and maintaining the integrity of the multifaceted representation of
      the body in the brain. Importantly, these advances have been found to prevent and
      reduce phantom limb pain. In particular, therapies that involve sensory and/or
      motor retraining, most naturally through the use of integrative prosthetic
      devices, as well as peripheral (e.g., transcutaneous electrical nerve
      stimulation) or central (e.g., transcranial magnetic stimulation or deep brain
      stimulation) stimulation techniques, have been found to both restore the neural
      representation of the missing limb and to reduce the intensity of phantom pain.
      While the evidence for the efficacy of these therapies is mounting, but well
      controlled and large-scale studies are still needed. WIREs Cogn Sci 2014, 5:221
      231. doi: 10.1002/wcs.1277 CONFLICT OF INTEREST: The authors have no financial or
      other relationship that might lead to a conflict of interest. For further
      resources related to this article, please visit the WIREs website. 

PMID- 26304310
TI  - Resting-state functional connectivity MRI reveals active processes central to
      cognition.
AB  - Analysis of spontaneously correlated low-frequency activity fluctuations across
      the brain using functional magnetic resonance imaging (MRI)-commonly referred to
      as resting-state functional connectivity (RSFC) MRI-was initially seen as a
      useful tool for mapping functional-anatomic networks in the living human brain,
      characterizing brain changes and differences in clinical populations, and
      studying comparative anatomy across species. However, little was known about the
      potential relevance of RSFC to cognitive processes. Indeed, there has been
      considerable controversy and debate as to the utility of studying the resting
      state in cognitive neuroscience. However, recent work has shown that RSFC, rather
      than merely reflecting passive or epiphenomenal activity within underlying
      functional-anatomic networks, reveals important dynamic processes that play an
      active role in cognition. RSFC has been associated with individual differences in
      a number of behavioral and cognitive domains, including perception, language,
      learning and memory, and the organization of conceptual knowledge. In this
      article, we review and integrate the latest research demonstrating that RSFC is
      functionally relevant to human behavior and higher-level cognition, and propose a
      hypothesis regarding its mechanism of action on functional network dynamics and
      cognition. We conclude that RSFC MRI will be an invaluable tool for future
      discovery of the fundamental neurocognitive interactions that underlie cognition.
      WIREs Cogn Sci 2014, 5:233-245. doi: 10.1002/wcs.1275 CONFLICT OF INTEREST: The
      authors have declared no conflicts of interest for this article. For further
      resources related to this article, please visit the WIREs website. 

PMID- 26304312
TI  - Stress, Immune Function and Collegiate Holiday Drinking: A Pilot Study.
AB  - BACKGROUND/AIMS: Social aspects of collegiate holiday drinking have been studied
      frequently, but physiological consequences are often overlooked. This study
      examined self-reported stress, endocrine and immune indicators in students at an
      American university before and after their week-long spring break (SB) holiday.
      METHODS: Participants (n = 27; 9 males) provided saliva samples and completed
      surveys pre- and post-SB. Based on their cortisol reaction to SB, participants
      were grouped as cortisol nonresponders (CNR; n = 14) or increasers (CI; n = 13).
      Groups were matched on demographics, baseline alcohol use, family history of
      alcoholism, and SB plans. Differences over time and between groups were examined
      for alpha-amylase, quantity/frequency of alcohol use (quantity/frequency index,
      QFI) and the immunoglobulin A (IgA) to albumin ratio (IgA:albumin). RESULTS:
      alpha-Amylase decreased over time. A time * group interaction was noted for QFI,
      in which CNRs increased drinking over SB, but CIs did not. Time and time * group
      effects occurred for IgA:albumin. CIs decreased IgA:albumin over SB, whereas CNRs
      did not. Pre-SB QFI and pre-/post-SB QFI changes were correlated with changes in
      IgA:albumin. CONCLUSION: These findings support previously published
      relationships between blunted cortisol responses and risk for problem drinking,
      as well as elevated cortisol and decreased immune response. These data also
      highlight the importance of physiological measures in the study of collegiate
      holiday drinking.

PMID- 26304313
TI  - Development of a high-performance liquid chromatography method based on a core
      shell column approach for the rapid determination of multiclass polyphenols in
      grape pomaces.
AB  - A rapid and economically affordable reverse-phase chromatographic approach based
      on a core-shell column with high-performance liquid chromatography multi
      wavelength detector (HPLC-MWD) is proposed for the quantification and quality
      control of multiclass polyphenols (PPs). The separation of 20 relevant
      polyphenols from grape pomace extracts (GPEs) was achieved in less than 12 min by
      using a Kinetex C18 column (3.0 mm * 100 mm, 2.6 MUm) with a gradient system of
      ultrapure water (0.1% formic acid) and acetonitrile, a temperature of 35  degrees
      C and a flow rate of 0.8 mL min(-1). The maximum backpressure reached was 327
      bar, meaning the developed method is adequate for standard HPLC instruments. The
      applicability of the method was demonstrated by the determination of PPs in GPEs
      of different red grape varieties. Cabernet Sauvignon GPE showed the highest
      content of studied PPs (9804.2 MUg g(-1)GPE) followed by Bonarda GPE (7302.0 MUg
      g(-1)GPE). Besides the methodological development for a high throughput routine
      quality control of GPEs, this is the first report of PPs content for Bonarda and
      Aspirant Bouchet GPE, so the results add knowledge for these grape varieties
      cultivated in Argentina.

PMID- 26304314
TI  - An efficient method for the simultaneous determination of furan, 2-methylfuran
      and 2-pentylfuran in fruit juices by headspace solid phase microextraction and
      gas chromatography-flame ionisation detector.
AB  - A headspace solid phase microextraction (HS-SPME) procedure followed by gas
      chromatography-flame ionisation detector (GC-FID) analysis was developed and
      validated for the simultaneous analysis of furan, 2-methylfuran and 2-pentylfuran
      from juice samples. Extraction at 32  degrees C for 20 min with stirring at 600
      rpm and NaCl concentration 15% (W/V) was the optimal HS-SPME condition for all
      the three compounds by using a carboxen/polydimethylsiloxane fused silica fibre
      (75 MUm). The extracted compounds were base line separated on a SPB-1 GC column
      within 12 min. The relative standard deviations of all analytes were less than
      6.7%. The recovery rates were between 90.2% and 110.1%. The limits of detection
      and limits of quantification were 0.056-0.23 ng/mL and 0.14-0.76 ng/mL,
      respectively. The results showed that the developed method was sensitive,
      precise, accurate and robust for the determination of furan, 2-methylfuran and 2
      pentylfuran in complex matrices without interferences from other components.

PMID- 26304315
TI  - Effect of pulsed electric fields assisted acetylation on morphological,
      structural and functional characteristics of potato starch.
AB  - Pulsed electric fields (PEF)-assisted acetylation of potato starch with different
      degree of substitution (DS) was prepared and effects of PEF strength, reaction
      time, starch concentration on DS were studied by response surface methodology.
      Results showed DS was increased from 0.054 (reaction time of 15 min) to 0.130
      (reaction time of 60 min) as PEF strength increased from 3 to 5 kV/cm. External
      morphology revealed that acetylated starch with higher DS was aggravated more
      bulges and asperities. Fourier-transformed infrared spectroscopy confirmed the
      introduction of acetyl group through a band at 1730 cm(-1). The optimum sample
      (DS =0 .13) had lower retrogradation (39.1%), breakdown (155 BU) and setback
      value (149BU), while pasting temperature (62.2  degrees C) was slightly higher
      than non-PEF-assisted samples. These results demonstrated PEF treatment can be a
      potential and beneficial method for acetylation and achieve higher DS with
      shorter reaction time.

PMID- 26304316
TI  - Effect of hydroxytyrosol on quality of sulfur dioxide-free red wine.
AB  - In this work, the feasibility of two commercial products enriched in
      hydroxytyrosol (HT) as alternative to sulfur dioxide in Syrah red wines was
      evaluated. The HT enriched products came from synthesis and from olive waste.
      Wines treated with HT were compared with wines treated with sulfur dioxide at two
      winemaking stages: bottling and after 6 months of storage in bottle. Minor
      differences were found in enological parameters and volatile composition (esters,
      alcohols and acids). Significant differences were observed in color related
      parameters and sensory analysis. HT wines improved color parameters as well as
      scents and tasting at bottling. However, after 6 months of storage in bottle HT
      wines were more oxidized than SO2 wines. The olfactometry profile of HT wines
      supported sensory analysis. HT wines showed new odorant zones from both the added
      product and oxidation.

PMID- 26304317
TI  - Gelatin hydrolysates from farmed Giant catfish skin using alkaline proteases and
      its antioxidative function of simulated gastro-intestinal digestion.
AB  - This work aims to evaluate the ability of different alkaline proteases to prepare
      active gelatin hydrolysates. Fish skin gelatin was hydrolysed by visceral
      alkaline-proteases from Giant catfish, commercial trypsin, and Izyme AL(r). All
      antioxidant activity indices of the hydrolysates increased with increasing degree
      of hydrolysis (P<0.05). The hydrolysates obtained with Izyme AL(r) and visceral
      alkaline-proteases showed the highest and lowest radical scavenging capacity,
      while prepared with commercial trypsin was the most effective in reducing ferric
      ions and showed the best metal chelating properties. The hydrolysate obtained
      with Izyme AL(r) showed the lowest iron reducing ability, but provided the
      highest average molecular weight (? 7 kDa), followed by commercial trypsin (2.2
      kDa) and visceral alkaline-proteases (1.75 kDa). After in vitro gastrointestinal
      digestion, the hydrolysates showed significant higher radical scavenging,
      reducing ferric ions and chelating activities. Gelatin hydrolysates, from fish
      skin, could serve as a potential source of functional food ingredients for health
      promotion.

PMID- 26304318
TI  - Effect of copper stress on growth characteristics and fermentation properties of
      Saccharomyces cerevisiae and the pathway of copper adsorption during wine
      fermentation.
AB  - The effect of copper stress on the fermentation performance of Saccharomyces
      cerevisiae and its copper adsorption pathway during alcoholic fermentation were
      investigated in this study. At the limits imposed by the regulations of the
      European Union and South African (? 20 mg/l), copper had no effect on the cell
      growth of S. cerevisiae, but its fermentation performance was inhibited to a
      certain extent. Therefore, the regulated limit should be further reduced (? 12.8
      mg/l). Under 9.6-19.2 mg/l copper stress, S. cerevisiae could absorb copper; the
      copper removal ratio and the unit strain adsorption were 60-81% and 2.72-9.65
      mg/g, respectively. S. cerevisiae has a non-biological adsorption of copper, but
      compared with biological (living yeast) adsorption, the non-biological adsorption
      was very low. The copper adsorption way of S. cerevisiae was primarily via
      biological (living yeast) adsorption, which was a two-step process.

PMID- 26304319
TI  - Comparison of modified starch and Quillaja saponins in the formation and
      stabilization of flavor nanoemulsions.
AB  - Modified starch (MS) and Quillaja saponins (QS) were compared to fabricate and
      stabilize orange oil nanoemulsions using microfluidization. Ester gum (EG) was
      incorporated in the oil phase at variable proportions (0-60%) as Ostwald ripening
      inhibitor and viscosity modifier. Optimal viscosity ratios of dispersed to
      continuous phase (etad/etac) were identified as 0.8-3.1 and 2.1-3.3 with MS and
      QS as emulsifier, respectively. QS was found superior to MS in fabricating
      nanoemulsion with smallest MDD of 69 nm and turbidity of 102 NTU at 0.05% of
      dispersed phase. With EG incorporated in the oil phase, QS stabilized
      nanoemulsions were stable during 2 weeks of storage at 23  degrees C; whereas MS
      stabilized nanoemulsions showed significant increases in MDD and turbidity. Zeta
      potential measurements showed QS imparted higher droplet charge (>-20 mV) than MS
      (<-5 mV) at pH 3.6 indicating MS stabilized nanoemulsions were destabilized by
      coalescence due to insufficient interfacial charge.

PMID- 26304320
TI  - Ion mobility spectrometry fingerprints: A rapid detection technology for
      adulteration of sesame oil.
AB  - A simple and rapid detection technology was proposed based on ion mobility
      spectrometry (IMS) fingerprints to determine potential adulteration of sesame
      oil. Oil samples were diluted by n-hexane and analyzed by IMS for 20s. Then,
      chemometric methods were employed to establish discriminant models for sesame
      oils and four other edible oils, pure and adulterated sesame oils, and pure and
      counterfeit sesame oils, respectively. Finally, Random Forests (RF)
      classification model could correctly classify all five types of edible oils. The
      detection results indicated that the discriminant models built by recursive
      support vector machine (R-SVM) method could identify adulterated sesame oil
      samples (? 10%) with an accuracy value of 94.2%. Therefore, IMS was shown to be
      an effective method to detect the adulterated sesame oils. Meanwhile, IMS
      fingerprints work well to detect the counterfeit sesame oils produced by adding
      sesame oil essence into cheaper edible oils.

PMID- 26304321
TI  - Considerations on the use of enzyme-assisted extraction in combination with
      pressurized liquids to recover bioactive compounds from algae.
AB  - Pressurized liquids, PLE, and enzyme-assisted extraction, EAE, have been tested
      to improve the extraction of phlorotannins from the seaweed Sargassum muticum.
      Enzymatic treatment with proteases and carbohydrases, alkaline hydrolysis and PLE
      with ethanol:water as extracting solvent have been studied in terms of extraction
      yield, total phenolic content and antioxidant activity (TEAC assay). Results
      demonstrated that the application of PLE alone provided the highest yields and
      relevant antioxidant activity. An experimental design was employed to further
      optimize the PLE extraction conditions; optimum parameters included the use of
      160  degrees C and 95% ethanol. Under these conditions, values of 21.9%, 94.0mg
      gallic acid equivalents g(-1), 5.018 mg phloroglucinol equivalents g(-1) and
      1.275 mmol trolox equivalents g(-1) were obtained for extraction yield, total
      phenols, total phlorotannins and TEAC, respectively. A preliminary chemical
      characterization by liquid chromatography coupled to mass spectrometry provided
      insight in terms of the mechanisms involved in the different processes.

PMID- 26304322
TI  - PTR-TOF-MS and HPLC analysis in the characterization of saffron (Crocus sativus
      L.) from Italy and Iran.
AB  - Saffron samples from Italy and Iran were analyzed for their content in aroma and
      bioactive compounds with different analytical techniques. HPLC was used for the
      identification and quantification of crocins, picrocrocin, safranal and
      flavonoids content, while the novel proton transfer reaction time-of-flight mass
      spectrometer was employed for the aroma compounds analysis. Italian saffron
      turned out to be richer in total crocins and safranal contents. Sample
      characterization was performed with an unsupervised statistical approach; tests
      involving different numbers of parameters deriving from the two analytical
      techniques were performed. The results achieved showed that the best samples
      classification was obtained by joining the information acquired from both
      techniques; following such an approach, a sharper separation between Iranian and
      Italian samples was achieved. Finally, among the variables that most contribute
      to the description of variability, isophorone, safranal and picrocrocin were
      identified to be the most significant. 

PMID- 26304323
TI  - Ultra high pressure homogenization of almond milk: Physico-chemical and
      physiological effects.
AB  - Ultra high pressure homogenization (UHPH) of food is a processing technology to
      improve food safety and shelf life. However, despite very short treatment
      duration UHPH may lead to changes in chemical and physico-chemical properties
      including formation of submicro-/nano-particles. This may affect the
      physiological or toxicological properties of the treated food. Here, we treated
      raw almond milk (AMr) with UHPH at 350 MPa and 85  degrees C (AMuhph), known able
      to inactivate food relevant microorganisms. UHPH-treatment led to about a
      threefold increase of the mean particle size. There was a nearly complete loss of
      antigenicity investigated by ELISA for determination of traces of almond
      proteins. The content of vitamins B1 and B2 remained unchanged, while free
      exposed sulfhydryl groups decreased. Despite of observed modifications, UHPH
      treatment of almond milk did not cause any changes in cyto- or genotoxic effects
      and antigenotoxic capability of protecting intestinal cells against iron induced
      DNA damage in vitro.

PMID- 26304324
TI  - Production of maize tortillas and cookies from nixtamalized flour enriched with
      anthocyanins, flavonoids and saponins extracted from black bean (Phaseolus
      vulgaris) seed coats.
AB  - Ethanolic extract from black beans coat is a source of flavonoids, saponins and
      antocyanins. Nixtamalized maize flours (NF) are used for the preparation of
      products such as tortillas, tortillas chips, cookies among others. The objective
      of this research was to study the effect on textural parameters and color after
      adding flavonoids, saponins and anthocyanins from black bean seed coat in NF used
      for the production of tortillas and gluten-free cookies. Furthermore, the
      retention of bioactive compounds after tortilla and gluten-free-cookie
      preparation was assessed. Ethanolic extracts of black bean seed coats were added
      (3g/kg or 7 g/kg) to NF in order to prepare corn tortillas and gluten free
      cookies characterized in terms of dimensions, color and texture. Addition of 7
      g/kg affected the color of cookies and tortillas without effect on texture and
      dimensions. It was possible to retain more than 80% and 60% of bioactives into
      baked tortillas and cookies, respectively.

PMID- 26304325
TI  - Monitoring the contents of six steroidal and phenolic endocrine disrupting
      chemicals in chicken, fish and aquaculture pond water samples using pre-column
      derivatization and dispersive liquid-liquid microextraction with the aid of
      experimental design methodology.
AB  - This research established a sensitive and efficient pre-column derivatization
      HPLC method based on dispersive liquid-liquid microextraction (DLLME) for the
      simultaneous determination of six steroidal and phenolic endocrine disrupting
      chemicals (EDCs). In this study, EDCs were firstly labeled by the derivatization
      reagent 2-(11H-benzo[a]carbazol-11-yl) ethyl carbonochloridate (BCEC-Cl) and then
      extracted by DLLME. The response surface methodology was employed to investigate
      the key parameters of pre-column derivatization and DLLME. Under the optimal
      conditions, a good linear relationship between the peak area and the
      concentration of analytes was observed with correlation coefficients of >0.9991.
      Limits of detection for all EDCs derivatives were achieved within the range of
      0.02-0.07 MUg L(-1). The proposed method has the advantages of simple operation,
      low consumption of organic solvent, saving time, low output limit and good
      selectivity. When applied to several food and water samples analysis, it
      demonstrated good applicability for the determination of EDCs.

PMID- 26304326
TI  - Enzymatic hydrolysis of ovomucin and the functional and structural
      characteristics of peptides in the hydrolysates.
AB  - Ovomucin was hydrolyzed using enzymes or by heating under alkaline conditions (pH
      12.0), and the functional, structural and compositional characteristics of the
      peptides in the hydrolysates were determined. Among the treatments, heating at
      100  degrees C for 15 min under alkaline conditions (OM) produced peptides with
      the highest iron-binding and antioxidant capacities. Ovomucin hydrolyzed with
      papain (OMPa) or alcalase (OMAl) produced peptides with high ACE-inhibitory
      activity. The mass spectrometry analysis indicated that most of the peptides from
      OMPa were <2 kDa, but peptides from OMTr and OM were >2 kDa. OMAl hydrolyzed
      ovomucin almost completely and no peptides within 700-5000 Da were found in the
      hydrolasate. The results indicated that the number and size of peptides were
      closely related to the functionality of the hydrolysates. Considering the time,
      cost and activities of the hydrolysates, OM was the best treatment for
      hydrolyzing ovomucin to produce functional peptides.

PMID- 26304327
TI  - Purification of free arginine from chickpea (Cicer arietinum) seeds.
AB  - Chickpea is a grain legume widely consumed in the Mediterranean region and other
      parts of the world. Chickpea seeds are rich in proteins but they also contain a
      substantial amount of free amino acids, especially arginine. Hence chickpea may
      represent a useful source of free amino acids for nutritional or pharmaceutical
      purposes. Arginine is receiving great attention in recent years because it is the
      substrate for the synthesis of nitric oxide, an important signaling molecule
      involved in numerous physiological and pathological processes in mammals. In this
      work we describe a simple procedure for the purification of arginine from
      chickpea seeds, using nanofiltration technology and an ion-exchange resin,
      Amberlite IR-120. Arginine was finally purified by precipitation or
      crystallization, yielding preparations with purities of 91% and 100%,
      respectively. Chickpea may represent an affordable green source of arginine, and
      a useful alternative to production by fermentation or protein hydrolysis. 

PMID- 26304328
TI  - Sulfur dioxide residue in sulfur-fumigated edible herbs: The fewer, the safer?
AB  - The residual content of sulfur dioxide is frequently regarded as the exclusive
      indicator in the safety evaluation of sulfur-fumigated edible herbs. To examine
      the feasibility of such assessment criteria, here the variations in residual
      sulfur dioxide content during sulfur-fumigation and the potential mechanisms
      involved were investigated, using Angelicae Sinensis Radix (ASR) as a model herb.
      The residual sulfur dioxide content and ten major bioactive components in sulfur
      fumigated ASR samples were dynamically examined at 13 successive time points
      within 72 h sulfur-fumigation. The relationship between the content variation
      tendency of sulfur dioxide and the ten chemicals was discussed. The results
      suggested that sulfur dioxide-involved chemical transformation of the original
      components in ASR might cause large consumption of residual sulfur dioxide during
      sulfur-fumigation. It implies that without considering the induced chemical
      transformation of bioactive components, the residual sulfur dioxide content alone
      might be inadequate to comprehensively evaluate the safety of sulfur-fumigated
      herbs.

PMID- 26304329
TI  - Kinetics of N(epsilon)-(carboxymethyl)lysine formation in aqueous model systems
      of sugars and casein.
AB  - This study investigated the formation of N(epsilon)-carboxymethyllysine (CML) in
      two caseinate solutions containing: (1) glucose, (2) lactose, each heated at 120 
      degrees C and 130  degrees C. At both heating temperatures, CML concentration in
      lactose-caseinate solution was higher than in glucose-caseinate solution. In both
      solutions, more CML was formed at 130  degrees C than at 120  degrees C. Using
      multiresponse modelling, two degradation routes for the sugars were confirmed:
      (1) isomerisation of glucose or lactose and subsequent degradation via Lobry de
      Bruyn-Alberda van Ekenstein (LA) arrangement; (2) the Maillard reaction between
      the reducing sugar and lysine residues. Modelling results suggested that CML was
      not formed from oxidation of the reducing sugars, but from the Maillard reaction
      via the Amadori rearrangement product. Since CML appeared to be thermally
      unstable under the current study conditions, it may not be a perfect indicator
      for heat damage of processed foods. This is the first study in which CML
      formation was linked to available information on the Maillard reaction via
      multiresponse modelling.

PMID- 26304330
TI  - Detection of cold injury in peaches by hyperspectral reflectance imaging and
      artificial neural network.
AB  - Peaches in cold storage may develop chill damage, as symptomized by deteriorated
      texture and lack of juice. To examine fruit quality, we established a
      hyperspectral imaging system to detect cold injury, and an artificial neural
      network (ANN) model was developed for which eight optimal wavelengths were
      selected. Between normal and chill-damaged peaches, significant differences in
      fruit quality parameters and the spectral response to correlating selected
      wavelengths were observed. Evidencing this relationship, the correlation
      coefficients between quality parameters and the respective spectral response of
      eight selected wavelengths were -0.587 to -0.700, 0.393 to 0.552, 0.510 to 0.751,
      and 0.574 to 0.773. With optimal representative wavelengths as inputs for the ANN
      model, the overall classification accuracy of chill damage was 95.8% for all cold
      stored samples. The ANN prediction models for quality parameters performed well,
      with correlation coefficients from 0.6979 to 0.9026. This research demonstrates
      feasibility of hyperspectral reflectance imaging technique for detecting cold
      injury. 

PMID- 26304331
TI  - Antioxidant and antiproliferative properties of 3-deoxyanthocyanidins.
AB  - The study of the antioxidant properties of six deoxyanthocyanidins
      (deoxypeonidin, deoxymalvidin, luteolinidin, apigeninidin,
      guaiacylcatechinpyrylium and syringylcatechinpyrylium) and an anthocyanin
      (cyanidin-3-glucoside) was carried out. The aim was to evaluate the relationship
      between the structure and the antioxidant properties of individual
      deoxyanthocyanidins, compared to a common anthocyanin derivative, cyanidin-3
      glucoside. The ability of these compounds to inhibit lipid peroxidation in a
      liposome membrane system was examined by monitoring oxygen consumption and the
      antiradical and reducing capacities were determined using the DPPH and FRAP
      assay, respectively. The results showed that all the compounds tested presented
      antioxidant properties. Cyanidin-3-glucoside presented higher antiradical and
      reducing activities in the DPPH and FRAP assay, although in the liposome model,
      the guaiacylcatechinpyrylium was more effective inhibiting lipid peroxyl
      radicals. Additionally, the anti-proliferative effects of deoxyanthocyanidins,
      have been evaluated against two cancer cell lines from stomach (AGS, MKN-28) and
      one colon cancer cell (Caco-2), and compared with the effect of the respective
      anthocyanins. Considering the antiproliferative activity, all compounds were
      active against Caco-2 cell line, being the ones with glucose moiety and oaklin
      Scp the most active. Deoxyanthocyanidins, and in particular,
      guaiacylcatechinpyrylium may be regarded as potential food colorants. 

PMID- 26304332
TI  - Physicochemical profiles of stingless bee (Apidae: Meliponini) honey from South
      East Asia (Thailand).
AB  - This study examines the physicochemical properties of stingless bee honey from SE
      Asia (Thailand). Twenty-eight stingless bee honey samples, from 11 stingless bee
      species, were examined. Results reveal an average color (67 +/- 19 mm Pfund),
      moisture (31 +/- 5.4 g/100g), ash (0.531 +/- 0.632 g/100g), electrical
      conductivity (1.1 +/- 0.780 ms/cm), pH of (3.6 +/- 0.198), total acidity (164 +/-
      162 meq/kg), diastase activity (1.5 +/- 1.6  degrees Gothe) and
      hydroxymethylfurfural (8.7 +/- 12 mg/kg). The carbohydrate profile is: total
      sugar (51 +/- 21 g/100g), fructose (17 +/- 9.7 g/100g), glucose (14 +/-
      8.6g/100g), maltose (41 +/- 15 g/100g) and sucrose (1.2 +/- 2.7 g/100g). These
      findings are not dissimilar to those reported for stingless bee honeys from the
      neo-tropics. When compared with the Apis mellifera standard, stingless bee honey
      is characterized as possessing higher moisture content, acidity, ash and HMF but
      a lower level of total sugars.

PMID- 26304333
TI  - Isolation and identification of antioxidant peptides from enzymatically
      hydrolyzed rice bran protein.
AB  - Khao Dawk Mali 105 rice bran protein (RBP) was fractionated into albumin (12.5%),
      globulin (13.9%), glutelin (70.8%) and prolamine (2.9%). The native and denatured
      RBP fractions were hydrolyzed with papain and trypsin for 3h at optimum
      conditions. The RBP fractions and their hydrolysates were evaluated for their
      antioxidant activity by the Oxygen Radical Absorbance Capacity (ORAC) assay. The
      trypsin-hydrolyzed denatured albumin exhibited the highest antioxidant activity
      with an ORAC value of 4.07 MUmol of Trolox equivalent (TE)/mg protein. This
      hydrolysate was separated by using RP-HPLC and three fractions with high
      antioxidant activity were examined by LTQ-FTICR ESI mass spectrometry. The MW of
      the peptides from these fractions were 800-2100 Da. and consisted of 6-21 amino
      acid residues. Most of the peptides from the fractions demonstrated typical
      characteristics of well-known antioxidant peptides. The results suggest that
      trypsin-hydrolyzed denatured rice bran albumin might be useful as a natural food
      antioxidant.

PMID- 26304334
TI  - Separation, concentration and determination of trace chloramphenicol in shrimp
      from different waters by using polyoxyethylene lauryl ether-salt aqueous two
      phase system coupled with high-performance liquid chromatography.
AB  - Polyoxyethylene lauryl ether (POELE10)-NaH2PO4 aqueous two-phase extraction
      system (ATPES) is coupled with HPLC to analyze chloramphenicol (CAP) in aquatic
      product. Response surface methodology (RSM) was adopted in the multi-factor
      experiment to determine the optimized conditions. The extraction efficiency of
      CAP (E%) is up to 99.42% under the optimal conditions, namely, the concentration
      of NaH2PO4, the concentration of POELE10, pH and temperature were 0.186 g . mL(
      1), 0.033 g . mL(-1), 3.8 and 25  degrees C respectively. The optimal value of
      enrichment factor of CAP (F) was 22.56 when the concentration of NaH2PO4 was
      0.192 g . mL(-1), the concentration of POELE10 was 0.024 g/ml, pH was 4.2 and
      temperature was 30  degrees C. The limit of detection (LOD) and limit of
      quantification (LOQ) of this method are 0.8 MUg . kg(-1) and 1 MUg . kg(-1),
      which meet the needs of determining trace or ultratrace CAP in food. The E% and F
      of this technique are much better than other extraction methods.

PMID- 26304335
TI  - Biotransformation of anthocyanins from two purple-fleshed sweet potato accessions
      in a dynamic gastrointestinal system.
AB  - Cooked, milled purple-fleshed sweet potato (PFSP) accessions, PM09.812 and
      PM09.960, underwent digestion in a dynamic human gastrointestinal (GI) model that
      simulates gut digestive conditions to study the bioaccessibility and
      biotransformation of anthocyanins. Matrix-assisted laser desorption ionization
      time-of-flight mass spectrometry showed accession-dependent variations in
      anthocyanin release and degradation. After 24h, more anthocyanin species were
      detected in the small intestinal vessel relative to other vessels for accession
      PM09.960 whereas more species appeared in the ascending colonic vessel for
      accession PM09.812. The ferric reducing antioxidant power was increased in the
      small intestinal vessel for PM09.960 and in the ascending colonic vessel for
      accession PM09.812, corresponding to the appearance of a majority of anthocyanins
      for each accession. These results show that intestinal and colonic microbial
      digestion of PFSP leads to an accession-dependent pattern for anthocyanin
      bioaccessibility and degradation. 

PMID- 26304336
TI  - Affinity of rosmarinic acid to human serum albumin and its effect on protein
      conformation stability.
AB  - Rosmarinic acid (RA) is a natural polyphenol contained in many aromatic plants
      with promising biological activities. The interaction between RA and human serum
      albumin (HSA) was investigated by multi-spectroscopic, electrochemistry,
      molecular docking and molecular dynamics simulation methods. The fluorescence
      emission of HSA was quenched by RA through a combined static and dynamic
      quenching mechanism, but the static quenching was the major constituent.
      Fluorescence experiments suggested that RA was bound to HSA with moderately
      strong binding affinity through hydrophobic interaction. The probable binding
      location of RA was located near site I of HSA. Additionally, as shown by the
      Fourier transform infrared (FT-IR) and circular dichroism (CD) spectra, RA can
      result in conformational and structural alterations of HSA. Furthermore, the
      molecular dynamics studies were used to investigate the stability of the HSA and
      HSA-RA system. Altogether, the results can provide an important insight for the
      applications of RA in the food industry. 

PMID- 26304337
TI  - Broad screening and identification of beta-agonists in feed and animal body fluid
      and tissues using ultra-high performance liquid chromatography-quadrupole
      orbitrap high resolution mass spectrometry combined with spectra library search.
AB  - Broad screening and identification of beta-agonists in feed, serum, urine, muscle
      and liver samples was achieved in a quick and highly sensitive manner using ultra
      high performance liquid chromatography-quadrupole-orbitrap high resolution mass
      spectrometry (UHPLC-Q-Orbitrap HRMS) combined with a spectra library search.
      Solid-phase extraction technology was employed for sample purification and
      enrichment. After extraction and purification, the samples were analyzed using a
      Q-Orbitrap high-resolution mass spectrometer under full-scan and data-dependent
      MS/MS mode. The acquired mass spectra were compared with an in-house library
      (compound library and MS/MS mass spectral library) built with TraceFinder
      Software which contained the M/Z of the precursor ion, chemical formula,
      retention time, character fragment ions and the entire MS/MS spectra of 32 beta
      agonist standards. Screening was achieved by comparing 5 key mass spectral
      results and positive matches were marked. Using the developed method, the
      identification results from 10 spiked samples and 238 actual samples indicated
      that only 2% of acquired mass spectra produced false identities. The method
      validation results showed that the limit of detection ranged from 0.021-3.854 MUg
      kg(-1)and 0.015-1.198 ng mL(-1) for solid and liquid samples, respectively.

PMID- 26304338
TI  - A novel electrochemical immunosensor for highly sensitive detection of aflatoxin
      B1 in corn using single-walled carbon nanotubes/chitosan.
AB  - A sensitive electrochemical immunosensor for aflatoxin B1 (AFB1) detection based
      on single-walled carbon nanotubes/chitosan was presented. The immunosensor was
      based on an indirect competitive binding to a fixed amount of anti-AFB1 between
      free AFB1 and AFB1-bovine serum albumin, which conjugate immobilized on
      covalently functionalized nanotubes/chitosan laid on the glass carbon electrode.
      Then, the anti-mouse immunoglobulin G secondary antibody labeled with alkaline
      phosphatase was bound to the electrode surface through reacting with primary
      antibody. Finally, alkaline phosphatase catalyzes the hydrolysis of the substrate
      alpha-naphthyl phosphate, which produced electrochemical signal. Compared with
      conventional methods, the established immunosensor was more sensitive and simple.
      Under optimal conditions, this method could quantitatively detect AFB1 from 0.01
      to 100 ng mL(-1) with a detection limit of 3.5 pg mL(-1). Moreover, the
      immunosensor was successfully applied to assay AFB1 in corn powder, which showed
      good correlation with the results obtained from high performance liquid
      chromatography.

PMID- 26304339
TI  - Purification and biochemical characterization of 11S globulin from chan (Hyptis
      suaveolens L. Poit) seeds.
AB  - Chan (Hyptis suaveolens) is a Mesoamerican crop highly appreciated since the pre
      Hispanic cultures. Its proteins are a good source of essential amino acids;
      however, there are no reports on the properties of its individual proteins. In
      this study, the 11S globulin (Hs11S) was purified and biochemically
      characterized. The molecular weight of native Hs11S was about 150-300 kDa with
      isoelectric points of 5.0-5.3, composed by four monomers of 53.5, 52, 51.1 and
      49.5 kDa, each formed by one acidic subunit and one basic subunit linked by a
      disulfide bond. Dynamic light scattering, size exclusion chromatography and
      native PAGE show that Hs11S is assembled in different oligomeric forms. LC-MS/MS
      analysis confirmed its identity. Hs11S presents antigenic determinants in common
      with lupin 11S globulin. Carbohydrate moieties or phosphate groups linked to
      Hs11S were not detected. This information is very useful in order to exploit and
      utilize rationally chan 11S globulin in food systems.

PMID- 26304340
TI  - Monitoring of twenty-two sulfonamides in edible tissues: Investigation of new
      metabolites and their potential toxicity.
AB  - The extensive and unregulated use of antibacterial drugs in animal farms in
      Lebanon can lead to detrimental consequences for the public health. To monitor
      the levels of sulfonamides and their metabolites in farms in Lebanon, a total of
      304 meat samples were collected and analyzed using liquid chromatography coupled
      to triple quadrupole and hybrid linear ion trap-Orbitrap mass spectrometry
      following QuEChERS-based extraction. Sulfonamide residues could be detected in
      forty-six samples, ten of which contained a concentration of sulfaquinoxaline
      (151.4-1196.7 MUg kg(-1) in chicken samples) and sulfadiazine (109.8 MUg kg(-1)
      in a beef sample) exceeding the European Union-based maximum residue level by 1
      12 folds, and thus were unfit for human consumption. Several acetylated,
      hydroxylated, and/or sulfated metabolites were identified, some of which were not
      previously detected in edible tissues. Most identified metabolites exhibited
      potential toxicity equivalent or higher than that of the parent molecule as
      estimated by in silico tests.

PMID- 26304341
TI  - Study on aggregation behavior of low density lipoprotein in hen egg yolk plasma
      by asymmetrical flow field-flow fractionation coupled with multiple detectors.
AB  - In this study, asymmetrical flow field-flow fractionation (AF4) coupled online
      with UV, multiangle light scattering (MALS), and fluorescence (FS) detectors (AF4
      UV-MALS-FS) was employed for separation and characterization of egg yolk plasma.
      AF4 provided separation of three major components of the egg yolk plasma i.e.
      soluble proteins, low density lipoproteins (LDL) and their aggregates, based on
      their respective hydrodynamic sizes. Identification of LDL was confirmed by
      staining the sample with a fluorescent dye, Nile Red. The effect of carrier
      liquids on aggregation of LDL was investigated. Collected fractions of soluble
      proteins were characterized using sodium dodecylsulfate polyacrylamide gel
      electrophoresis (SDS-PAGE). Moreover, the effect of heat and enzymatic treatment
      on egg yolk plasma was investigated. The results suggest that enzymatic treatment
      with phospholipase A2 (PLA2) significantly enhances the heat stability of LDL.
      The results show that AF4-UV-MALS-FS is a powerful tool for the fractionation and
      characterization of egg yolk plasma components. 

PMID- 26304342
TI  - Enzyme-assisted extraction for the HPLC determination of aflatoxin M1 in cheese.
AB  - The extraction of aflatoxin M1 (AFM1) from cheese is generally carried out using
      chlorinated organic solvents. In this study, two innovative methods were
      developed, based on an enzyme-assisted (EA) extraction using proteolytic enzymes
      (pepsin or pepsin-pancreatin). After purification through an immunoaffinity
      column, AFM1 is determined by HPLC-FLD. A comparison between the new EA methods
      and an established chloroform (CH) method was carried out on 24 cheese samples.
      The results showed that the extraction efficiency of the EA methods was
      independent of ripening time of cheese, whereas the CH method was not able to
      fully recover AFM1 from ripened cheeses. The simpler (pepsin) of the two methods
      has been adopted by our laboratory for routine analysis of AFM1 in cheese. In
      comparison with the CH method, the pepsin-HCl (P-HCl) method is simpler, avoiding
      solvent evaporation, dissolution and partition in a separating funnel; moreover,
      it gives higher recoveries, comparable LOD and LOQ and more accurate results. 

PMID- 26304343
TI  - An elemental analysis of conventionally, organically and self-grown carrots.
AB  - Conventionally-, organically- and self-grown carrots available across the Czech
      market were characterised based on their elemental, nitrate and dry matter
      content (218 samples, 20 parameters) in order to assess the quality of the
      carrots and address the question whether organic also means better. The results
      were compared with information describing the elemental composition of carrots
      published previously, recommended daily intakes, and legislative limits for
      contaminants in food. Significant differences in the amounts of Na, K, S, Al, Mn,
      Ni, As and Cd were observed between conventional and organic carrots. From the
      perspective of inter-element interactions, and the origin of these, a principal
      components analysis of the datasets found no significant differences between
      conventionally- and organically-grown carrots. For the consumer, it is valuable
      to know there are no differences between conventionally- and organically-grown
      carrots, and no potential harm arising from heavy metal contamination. Based on
      our data, carrots are an excellent source of potassium. 

PMID- 26304344
TI  - Rapid screening and identification of compounds with DNA-binding activity from
      Folium Citri Reticulatae using on-line HPLC-DAD-MS(n) coupled with a post column
      fluorescence detection system.
AB  - To study the interactions between natural compounds and deoxyribonucleic acid
      (DNA), a method has been established combining a high-performance liquid
      chromatography-diode array detector-multi-stage mass spectrometer with a
      fluorescence detector (HPLC-DAD-MS(n)-FLD). The FLD was used to monitor
      fluorescence intensity of the ethidium bromide-DNA (EB-DNA) complex when a
      compound separated by HPLC was introduced. This novel method was used to
      simultaneously obtain the HPLC fingerprint, UV spectra, MS(n) fragments and DNA
      binding activity profile of various components in Folium Citri Reticulatae. As a
      result, 35 compounds were identified, of which 25 were found in the extract of
      Folium Citri Reticulatae for the first time, and 33 compounds showed DNA-binding
      activities, with the most active being feruloylhexaric and p-coumaroylhexaric
      acids. In addition, the precision, stability and reproducibility of this method
      were validated by two positive controls, quercetin and hesperidin. This new on
      line method is accurate, precise and reliable for further high-throughput
      screening of DNA-binding compounds from food samples and other complex matrices. 

PMID- 26304345
TI  - Molecularly imprinted calixarene fiber for solid-phase microextraction of four
      organophosphorous pesticides in fruits.
AB  - Calixarene was used as a functional monomer to fabricate a molecularly imprinted
      polymer (MIP) by sol-gel technique for solid-phase microextraction (SPME) of
      parathion-methyl and its structural analogs. The MIP-coated fiber possessed
      excellent thermal and chemical stability as well as high extraction capacity. Its
      selectivity and possible recognition mechanism were investigated. The
      similarities in molecular shape and functional group play a key role in the
      selective recognition of the imprinted material. Any changes to the structure of
      the template would decrease the imprinting factor. A comparison of MIP-SPME was
      made with liquid-liquid extraction coupled with gas chromatography for the
      determination of organophosphorus pesticides (OPPs) in fruits. Much lower limits
      of detection and better recoveries were achieved by SPME in spiked apple and
      pineapple samples. The experiment demonstrates that the proposed method using the
      calixarene MIP fiber was more suitable for selective determination of trace OPPs
      in those fruit samples. 

PMID- 26304346
TI  - Development of a rapid and direct method for the determination of organic acids
      in peach fruit using LC-ESI-MS.
AB  - An accurate, simple and rapid liquid chromatography mass spectrometry method for
      the determination of organic acids in peach fruit has been developed. Direct
      injection and sample clean-up with a mixed-mode sorbent was compared. The best
      results for the determination of gluconic, oxalic, malic, citric and fumaric
      acids were obtained with only a simple dilution and filtration step, and nylon
      filters should be avoided since some organic acids are retained by them. It is
      the first time that gluconic acid has been determined in peach fruit. Different
      parameters involved in the separation and detection process have been optimized.
      Since matrix effects were observed in the peach commodity, organic acids were
      quantified by the standard addition method. All validation parameters of the
      method were found acceptable of all organic acids. Finally, the method was
      successfully applied to the analysis of samples of peach from two cultivars. 

PMID- 26304347
TI  - Determination of As, Hg and Pb in herbs using slurry sampling flow injection
      chemical vapor generation inductively coupled plasma mass spectrometry.
AB  - Analysis of herbs for As, Hg and Pb has been carried out using slurry sampling
      inductively coupled plasma mass spectrometry (ICP-MS) with flow injection vapor
      generation. Slurry containing 0.5% m/v herbal powder, 0.1% m/v citric acid and 2%
      v/v HCl was injected into the VG-ICP-MS system for the determination of As, Hg
      and Pb that obviate dissolution and mineralization. Standard addition and isotope
      dilution methods were used for quantifications in selected herbal powders. This
      method has been validated by the determination of As, Hg and Pb in NIST standard
      reference materials SRM 1547 Peach Leaves and SRM 1573a Tomato Leaves. The As, Hg
      and Pb analysis results of the reference materials agreed with the certified
      values. The precision obtained by the reported procedure was better than 7% for
      all determinations. The detection limit estimated from standard addition curve
      was 0.008, 0.003, and 0.007 ng mL(-1) for As, Hg and Pb, respectively.

PMID- 26304348
TI  - Simultaneous determination of nitroimidazoles, benzimidazoles, and
      chloramphenicol components in bovine milk by ultra-high performance liquid
      chromatography-tandem mass spectrometry.
AB  - A sensitive, confirmatory ultra-high performance liquid chromatography-tandem
      mass spectrometric method was developed and validated to detect 23 veterinary
      drugs and metabolites (nitroimidazoles, benzimidazoles, and chloramphenicol
      components) in bovine milk. Compounds of interest were sequentially extracted
      from milk with acetonitrile and basified acetonitrile using sodium chloride to
      induce liquid-liquid partition. The extract was purified on a mixed mode solid
      phase extraction cartridge. Using rapid polarity switching in electrospray
      ionization, a single injection was capable of detecting both positively and
      negatively charged analytes in a 9 min chromatography run time. Recoveries based
      on matrix-matched calibrations and isotope labeled internal standards for milk
      ranged from 51.7% to 101.8%. The detection limits and quantitation limits of the
      analytical method were found to be within the range of 2-20 ng/kg and 5-50 ng/kg,
      respectively. The recommended method is simple, specific, and reliable for the
      routine monitoring of nitroimidazoles, benzimidazoles, and chloramphenicol
      components in bovine milk samples.

PMID- 26304349
TI  - Practical problems when using ABTS assay to assess the radical-scavenging
      activity of peptides: Importance of controlling reaction pH and time.
AB  - Effects of reaction pH and time on the antioxidant behaviors of Tyr, Trp, Cys,
      and their related peptides (Tyr-Gly, Tyr-Glu, Tyr-Lys, Trp-Gly, Trp-Glu, Trp-Lys,
      Cys-Gly and Cys-Gly) in ABTS assay were investigated. Results showed that all
      these amino acids and peptides displayed a biphasic kinetic pattern with a fast
      initial step and a slow secondary step. The initial reaction rates of Tyr, Trp
      and their related peptides were strongly dependent on pH, while those of Cys and
      Cys-containing peptides were unaffected by pH. They failed to reach equilibrium
      over the short incubation period of 6-10 min typically used in this assay. Longer
      incubation time was needed for most of the peptides to approach equilibrium at
      lower pH. The observed biphasic kinetic pattern as well as the high TEAC values
      for these amino acids and peptides, could be a result of combined antioxidant
      behaviors of themselves plus the generated reaction products.

PMID- 26304350
TI  - Microwave plasma atomic emission spectrometric determination of Ca, K and Mg in
      various cheese varieties.
AB  - Microwave plasma-atomic emission spectrometry (MP-AES) was used to determine
      calcium, magnesium and potassium in various Turkish cheese samples. Cheese
      samples were dried at 100  degrees C for 2 days and then digested in a mixture of
      nitric acid/hydrogen peroxide (3:1). Good linearities (R(2) > 0.999) were
      obtained up to 10 MUg mL(-1) of Ca, Mg and K at 445.478 nm, 285.213 nm and
      766.491 nm, respectively. The analytes in a certified reference milk powder
      sample were determined within the uncertainty limits. Moreover, the analytes
      added to the cheese samples were recovered quantitatively (>90%). All
      determinations were performed using aqueous standards for calibration. The LOD
      values for Ca, Mg and K were 0.036 MUg mL(-1), 0.012 MUg mL(-1) and 0.190 MUg mL(
      1), respectively. Concentrations of Ca, K and Mg in various types of cheese
      samples produced in different regions of Turkey were found between 1.03-3.70,
      0.242-0.784 and 0.081-0.303 g kg(-1), respectively.

PMID- 26304351
TI  - A simple extraction method for the simultaneous detection of tetramisole and
      diethylcarbamazine in milk, eggs, and porcine muscle using gradient liquid
      chromatography-tandem mass spectrometry.
AB  - Analysis of residual quantities of contaminants in foods of animal origin is
      crucial for quality control of consumer products. This study was aimed to develop
      a simple and raid analytical method for detection of tetramisole and
      diethylcarbamazine using gradient liquid chromatography coupled with tandem mass
      spectrometry (LC/MS/MS). Tetramisole, diethylcarbamazine, and guaifenesin (as an
      internal standard) were extracted from milk, eggs, and porcine muscle using
      acetonitrile followed by partitioning at -20  degrees C for 1h. No extract
      purification was deemed necessary. The analytes were separated on C18 column
      using ammonium formate both in water and methanol. Good linearity was achieved
      over the tested concentration range with R(2) ? 0.974. Recovery at two
      fortification levels ranged between 67.47% and 97.38%. The intra- and inter-day
      precisions were <20%. The limit of quantification was 0.2 and 2 ng/g for
      tetramisole and diethylcarbamazine, respectively. An analytical survey of samples
      purchased from large markets showed that none of the samples contained any of the
      target analytes. To the best of our knowledge, this is the first report on the
      quantitative determination of tetramisole and diethylcarbamazine in animal food
      products.

PMID- 26304352
TI  - Bioassay-guided isolation of proanthocyanidins with antioxidant activity from
      peanut (Arachis hypogaea) skin by combination of chromatography techniques.
AB  - Purification and bioassay-guided fractionation were employed to isolate
      proanthocyanidins with antioxidant activity from peanut skin (Arachis hypogaea
      Runner 886). The crude extract was prepared with acetone (60% v/v) and purified
      using chromatographic methods, including a semipreparative HPLC technique. As a
      result, two proanthocyanidins were isolated and identified using NMR, epicatechin
      (2 beta -> O -> 7, 4 beta -> 8)-catechin (proanthocyanidin A1) and epicatechin
      (beta -> 2 O -> 7, 4 beta -> 8)-epicatechin (proanthocyanidin A2). Despite the
      structural similarity, differences were observed in their antioxidant activity.
      Proanthocyanidin A1 proved to be more active, with EC50 value for DPPH radical
      scavenging of 18.25 MUg/mL and reduction of Fe(3+)-TPTZ complex of 7.59 mmol/g,
      higher than that of synthetic antioxidant BHT. This compound evaluated by ABTS(+)
      was similar to that of natural quercetin. Therefore, peanut skin is an important
      source of bioactive compounds that may be used as a mild antioxidant for food
      preservation.

PMID- 26304353
TI  - Quantitative analysis of amoxicillin, its major metabolites and ampicillin in
      eggs by liquid chromatography combined with electrospray ionization tandem mass
      spectrometry.
AB  - In this present study, we developed a simple, rapid and specific method for the
      quantitative analysis of the contents of amoxicillin (AMO), AMO metabolites and
      ampicillin (AMP) in eggs. This method uses a simple liquid-liquid extraction with
      acetonitrile followed by liquid chromatography-tandem mass spectrometry (LC
      MS/MS). The optimized method has been validated according to requirements defined
      by the European Union and Food and Drug Administration. Extraction recoveries of
      the target compounds from the egg at 5, 10 and 25 MUg/kg were all higher than
      80%, with relative standard deviations not exceeding 10.00%. The limits of
      quantification in eggs were below the maximum residue limits (MRLs). The decision
      limits (CCalpha) ranged between 11.1 and 11.5 MUg/kg, while detection
      capabilities (CCbeta) from 12.1 to 13.0 MUg/kg. These values were very close to
      the corresponding MRLs. Finally, the new approach was successfully verified for
      the quantitative determination of these analytes in 40 commercial eggs from local
      supermarkets.

PMID- 26304354
TI  - Dynamic high pressure microfluidization-assisted extraction and bioactivities of
      Cyperus esculentus (C. esculentus L.) leaves flavonoids.
AB  - The aim of this work was to study the effect of dynamic high pressure
      microfluidization (DHPM) on extracting total flavonoids from Cyperus esculentus
      L. (C. esculentus L.) leaves and to evaluate the antioxidant activity and
      antibacterial property of these flavonoids. In all the assays, pretreatment with
      DHPM was found to not only efficiently improve the yield of total flavonoids but
      also strengthen the antioxidant activity of the total flavonoids. C. esculentus
      L. leaves flavonoids had pronounced antioxidant activity in vivo that could
      significantly elevate the content of superoxide dismutase (SOD) without
      increasing the malondialdehyde (MDA) levels, and could also improve total
      antioxidant capacity in mice with a dose-dependent fashion. C. esculentus L.
      leaves flavonoids inhibited the growth of both Gram positive and Gram negative
      bacteria while no obvious inhibitory effect on Penicillium and Aspergillus could
      be observed. Our studies indicate that flavonoids from C. esculentus L. leaves
      can be taken as a natural antioxidant and bacteriostatic substance in food and
      pharmaceutical industry. 

PMID- 26304355
TI  - The effect of high-pressure processing on colour, bioactive compounds, and
      antioxidant activity in smoothies during refrigerated storage.
AB  - The effects of high-pressure processing--HPP--(450 and 600 MPa/3 min/20  degrees
      C) on the colour, carotenoids, ascorbic acid, polyphenols and antioxidant
      activity (FRAP and DPPH) of a smoothie were compared to thermal processing (80 
      degrees C/3 min). Stability during 45 days at 4  degrees C was also evaluated.
      HPP samples showed slight differences (p < 0.05) in colour compared to untreated
      smoothies. Both HPP significantly increased the extractability of lycopene, beta
      carotene and polyphenols compared to untreated samples. After HPP, ascorbic acid
      was retained by more than 92% of the initial content. The best results for
      antioxidant activity were obtained when HPP was applied at 600 MPa. FRAP and DPPH
      showed a high correlation with ascorbic acid (R(2) = 0.7135 and 0.8107,
      respectively) and polyphenolic compounds (R(2) = 0.6819 and 0.6935,
      respectively), but not with total carotenoids. Changes in bioactive compounds
      during the storage period were lower in the HPP smoothie than in the thermal
      treated sample.

PMID- 26304356
TI  - Development of qualitative and quantitative PCR analysis for meat adulteration
      from RNA samples.
AB  - Total RNA samples were used to establish qualitative and quantitative PCR-based
      methods for assessing meat adulteration. The primers were designed based on the
      mRNA sequences of troponin I (TnI), mitochondrial ribosomal protein (MRP) and
      tropomodulin genes to distinguish chicken, pork, goat, beef and ostrich. There
      was no cross reaction between the primers, and the detection limit of the cDNA
      template was 0.01 and 20 ng in simplex PCR and multiplex PCR, respectively. In
      the low temperature storage test, the detection limits of cDNA template with 10
      and 1 ng were determined at 4  degrees C and -80  degrees C. In quantitative
      assay, the precision of real-time PCR analysis expressed as a coefficient of
      variation (CV) ranged from 0.25% to 5.24% and the trueness, expressed as an
      error, ranged from 0.28% to 6.98% for adulteration. Thus, herein, we provided
      alternative tools for the assessment of meat adulteration using mRNA-based PCR
      methods.

PMID- 26304357
TI  - Determination of mutagenic amines in water and food samples by high pressure
      liquid chromatography with amperometric detection using a multiwall carbon
      nanotubes-glassy carbon electrode.
AB  - A chromatographic method, using amperometric detection, for the sensitive
      determination of six representative mutagenic amines was developed. A glassy
      carbon electrode (GCE), modified with multiwall carbon nanotubes (GCE-CNTs), was
      prepared and its response compared to a conventional glassy carbon electrode. The
      chromatographic method (HPLC-GCE-CNTs) allowed the separation and the
      determination of heterocyclic aromatic amines (HAAs) classified as mutagenic
      amines by the International Agency for Research of Cancer. The new electrode was
      systematically studied in terms of stability, sensitivity, and reproducibility.
      Statistical analysis of the obtained data demonstrated that the modified
      electrode provided better sensitivity than the conventional unmodified ones.
      Detection limits were in the 3.0 and 7.5 ng/mL range, whereas quantification
      limits ranged between 9.5 and 25.0 ng/mL were obtained. The applicability of the
      method was demonstrated by the determination of the amines in several types of
      samples (water and food samples). Recoveries indicate very good agreement between
      amounts added and those found for all HAAs (recoveries in the 92% and 105%
      range).

PMID- 26304358
TI  - Simultaneously determination of trace Cd(2+) and Pb(2+) based on L
      cysteine/graphene modified glassy carbon electrode.
AB  - In this paper, L-cysteine/graphene-CS/GCE (L-cys/GR-CS/GCE) was prepared
      successfully, and its electrochemical properties were characterized by cyclic
      voltammetry (CV) and electrochemical AC impedance. Moreover, the electrochemical
      behaviors of Cd(2+) and Pb(2+) on the proposed electrode were studied by
      differential pulse anodic stripping voltammetry (DPASV). Experimental parameters,
      such as the deposition potential and time, the pH value of buffer solution, were
      optimized. Under the optimized conditions, the linear equations of the DPASV
      response current with Cd(2+) and Pb(2+) concentration were I (MUA) = 0.745 C
      (MUg/L)+4.539 (R = 0.9986), I (MUA) = 0.437 C (MUg/L)+2.842 (R = 0.9983),
      respectively, and the detection limit was 0.45 and 0.12 MUg/L, respectively.
      Finally, L-cys/GR-CS/GCE was used to detect Cd(2+) and Pb(2+) in practical
      samples, and the results were compared with ICP-AES. This idea and method will
      provide a new approach for food security evaluation.

PMID- 26304360
TI  - The effect of extrusion processing on the physiochemical properties of extruded
      orange pomace.
AB  - Soluble dietary fibre (SDF) is considered the most effective fraction of dietary
      fibre (DF) for human health. In this study, extrusion technology was applied to
      enhance the SDF obtained from orange pomace, a byproduct of juice extraction
      containing a high level of DF. The pomace was processed in a single-screw
      extruder at various barrel temperatures (X1; 115-135  degrees C), feed moistures
      (X2; 10-18 g/100g), and screw speeds (X3; 230-350 rpm). Based on response surface
      methodology, the optimum extrusion conditions, which produced a maximum SDF value
      of 30.36%, were as follows: barrel temperature, 129  degrees C; feed moisture,
      15%; and screw speed, 299 rpm. Compared with unextruded pomace, SDF fraction in
      extrudate had a higher level of uronic acid. Furthermore, the extrusion process
      improved the physicochemical properties of extrudate, increasing the water
      holding capacity, swelling, water solubility index, and cation-exchange capacity
      and decreasing the oil-holding capacity.

PMID- 26304359
TI  - ROS production in homogenate from the body wall of sea cucumber Stichopus
      japonicus under UVA irradiation: ESR spin-trapping study.
AB  - Sea cucumber Stichopus japonicus (S. japonicus) shows a strong ability of
      autolysis, which leads to severe deterioration in sea cucumber quality during
      processing and storage. In this study, to further characterize the mechanism of
      sea cucumber autolysis, hydroxyl radical production induced by ultraviolet A
      (UVA) irradiation was investigated. Homogenate from the body wall of S. japonicas
      was prepared and subjected to UVA irradiation at room temperature. Electron Spin
      Resonance (ESR) spectra of the treated samples were subsequently recorded. The
      results showed that hydroxyl radicals (OH) became more abundant while the time of
      UVA treatment and the homogenate concentration were increased. Addition of
      superoxide dismutase (SOD), catalase, EDTA, desferal, NaN3 and D2O to the
      homogenate samples led to different degrees of inhibition on OH production. Metal
      cations and pH also showed different effects on OH production. These results
      indicated that OH was produced in the homogenate with a possible pathway as
      follows: O2(-) -> H2O2 -> OH, suggesting that OH might be a critical factor in
      UVA-induced S. japonicus autolysis.

PMID- 26304361
TI  - Quantification of applied dose in irradiated citrus fruits by DNA Comet Assay
      together with image analysis.
AB  - The experiments were conducted for quantification of applied dose for quarantine
      control in irradiated citrus fruits. Citrus fruits exposed to doses of 0.1 to 1.5
      kGy and analyzed by DNA Comet Assay. Observed comets were evaluated by image
      analysis. The tail length, tail moment and tail DNA% of comets were used for the
      interpretation of comets. Irradiated citrus fruits showed the separated tails
      from the head of the comet by increasing applied doses from 0.1 to 1.5 kGy. The
      mean tail length and mean tail moment% levels of irradiated citrus fruits at all
      doses are significantly different (p < 0.01) from control even for the lowest
      dose at 0.1 kGy. Thus, DNA Comet Assay may be a practical quarantine control
      method for irradiated citrus fruits since it has been possible to estimate the
      applied low doses as small as 0.1 kGy when it is combined with image analysis.

PMID- 26304362
TI  - Using UV-Vis spectroscopy for simultaneous geographical and varietal
      classification of tea infusions simulating a home-made tea cup.
AB  - In this work we proposed a method to verify the differentiating characteristics
      of simple tea infusions prepared in boiling water alone (simulating a home-made
      tea cup), which represents the final product as ingested by the consumers. For
      this purpose we used UV-Vis spectroscopy and variable selection through the
      Successive Projections Algorithm associated with Linear Discriminant Analysis
      (SPA-LDA) for simultaneous classification of the teas according to their variety
      and geographic origin. For comparison, KNN, CART, SIMCA, PLS-DA and PCA-LDA were
      also used. SPA-LDA and PCA-LDA provided significantly better results for tea
      classification of the five studied classes (Argentinean green tea; Brazilian
      green tea; Argentinean black tea; Brazilian black tea; and Sri Lankan black tea).
      The proposed methodology provides a simpler, faster and more affordable
      classification of simple tea infusions, and can be used as an alternative
      approach to traditional tea quality evaluation as made by skilful tasters, which
      is evidently partial and cannot assess geographic origins. 

PMID- 26304363
TI  - Effects of brewing conditions on the antioxidant capacity of twenty-four
      commercial green tea varieties.
AB  - A novel paper-based Nanoceria Reducing Antioxidant Capacity (NanoCerac) assay for
      antioxidant detection (Sharpe, Frasco, Andreescu, & Andreescu, 2012), has been
      adapted for the first time as a high-throughput method, in order to measure the
      effect of brewing conditions and re-infusion on the antioxidant capacity of
      twenty-four commercial green teas. The oxygen radical absorbance capacity (ORAC)
      assay, frequently applied to complex foods and beverages, was used as a
      comparator measure of antioxidant capacity. A novel measure of sustained
      antioxidant capacity, the total inherent antioxidant capacity (TI-NanoCerac and
      TI-ORAC) was measured by infusing each tea six times. Effects of brewing
      conditions (temperature, brew time, etc.) were assessed using one popular tea as
      a standard. Both NanoCerac and ORAC assays correlated moderately (R(2) 0.80 +/-
      0.19). The average first-brew NanoCerac, TI-NanoCerac, first-brew ORAC and TI
      ORAC were: 0.73 +/- 0.1 GAE/g tea; 2.4 +/- 0.70 mmolGAE/g tea; 1.0 +/- 0.3
      mmolTE/g tea and 2.1 +/- 0.71 mmolTE/g tea respectively. Brewing conditions
      including water temperature and infusion time significantly affected antioxidant
      capacity. The high-throughput adaptation of the original NanoCerac assay tested
      here offered advantages over ORAC, including portability and rapid analysis.

PMID- 26304364
TI  - Rapid analysis of biogenic amines from rice wine with isotope-coded
      derivatization followed by high performance liquid chromatography-tandem mass
      spectrometry.
AB  - A pair of isotope-coded derivatization reagents, d0-10-methyl-acridone-2-sulfonyl
      chloride (d0-MASC, light form) and d3-10-methyl-acridone-2-sulfonyl chloride (d3
      MASC, heavy form), were used for labeling biogenic amines (BAs). On basis of the
      isotope-coded derivatization, a global isotope internal standard quantitative
      method for determining seven BAs by high-performance liquid chromatography-tandem
      mass spectrometry (HPLC-MS/MS) was developed. The d0-MASC and d3-MASC can easily
      label BAs under mild conditions within 15 min at 50  degrees C. The obtained
      light and heavy labeled BAs were monitored by the transitions of [M+H](+) -> 208
      and [M+H](+) -> 211, respectively. Relative quantification of BAs was achieved by
      calculation of the peak area ratios of d0-MASC/d3-MASC labeled derivatives.
      Excellent linear responses for relative quantification were observed in the range
      of 1/10-10/1. The developed method has been successfully applied to the
      quantification of BAs in Chinese rice wine with recoveries ranging from 94.9% to
      104.5%.

PMID- 26304365
TI  - Location of TEMPO derivatives in micelles: subtle effect of the probe
      orientation.
AB  - Partition coefficients for six 4-substituted derivatives of the 2,2,6,6
      tetramethylpiperidine-N-oxyl (TEMPO) derivatives in aqueous solutions of reduced
      Triton X-100 (RTX-100) were determined by measurements of the probe EPR g-factor
      and of the fluorescence quenching of pyrene by the radical in the micelle. The
      partition constant attained a maximum value and then decreased with increasing
      probe hydrophobicity. Simulation of the probes inside the micelle showed that
      this trend could be rationalized by a change in the orientation of the 4
      substituted TEMPO derivatives with the increasing substituent chain-length. The
      use of the EPR g-factor for the determination of partition constants of radicals
      in micellar systems was thus validated as a reliable and sensitive method,
      capable of describing the probe orientation in its microenvironment. 

PMID- 26304366
TI  - Analysis of vitamin K1 in fruits and vegetables using accelerated solvent
      extraction and liquid chromatography tandem mass spectrometry with atmospheric
      pressure chemical ionization.
AB  - The objective of this study was to develop a rapid, sensitive, and specific
      analytical method to study vitamin K1 in fruits and vegetables. Accelerated
      solvent extraction and solid phase extraction was used for sample preparation.
      Quantification was done by liquid chromatography tandem mass spectrometry with
      atmospheric pressure chemical ionization in selected reaction monitoring mode
      with deuterium-labeled vitamin K1 as an internal standard. The precision was
      estimated as the pooled estimate of three replicates performed on three different
      days for spinach, peas, apples, banana, and beetroot. The repeatability was 5.2%
      and the internal reproducibility was 6.2%. Recovery was in the range 90-120%. No
      significant difference was observed between the results obtained by the present
      method and by a method using the same principle as the CEN-standard i.e. liquid
      liquid extraction and post-column zinc reduction with fluorescence detection.
      Limit of quantification was estimated to 0.05 MUg/100g fresh weight.

PMID- 26304367
TI  - In vitro digestion of luteinizing hormone releasing hormone analog (LHRHa) using
      simulated gastric conditions in assessing human food safety.
AB  - Luteinizing hormone releasing hormone analog (LHRHa, des Gly10, [D-Ala6]
      ethylamide) is routinely applied for induced spawning of fish. Simulated gastric
      acid and pepsin were used to mimic human digestion in vitro to determine the
      stability of LHRHa upon possible ingestion. In vitro cleavage of LHRHa was
      quantified using UPLC-MS, ultra-performance liquid chromatography-mass
      spectrometry. LHRHa was broken down mainly into two fragments from Glp-His-Trp
      Ser-Tyr-D-Ala-Leu-Arg-Pro-NHEt (LHRHa) to Trp-Ser-Tyr-D-Ala-Leu-Arg-Pro-NHEt
      (fragment 1) and Ser-Tyr-D-Ala-Leu-Arg-Pro-NHEt (fragment 2). By 24h of
      incubation, LHRHa was completely digested or barely detectable if the starting
      material was at 250 ng/MUl. If the starting concentration was at 5 ng/MUl, LHRHa
      was completely digested by 5h of incubation, or earlier. In both extreme
      scenarios, the results indicated that LHRHa would be digested completely in the
      human stomach and would pose no risk in human food consumption. This study
      supports the assertion that LHRHa used as a spawning aid would not pose a human
      food safety risk.

PMID- 26304368
TI  - Protein denaturation of whey protein isolates (WPIs) induced by high intensity
      ultrasound during heat gelation.
AB  - In this study, the impact of high intensity ultrasound (HIU) on proteins in whey
      protein isolates was examined. Effects on thermal behavior, secondary structure
      and nature of intra- and intermolecular bonds during heat-induced gelling were
      investigated. Ultrasonication (24 kHz, 300 W/cm(2), 2078 J/mL) significantly
      reduced denaturation enthalpies, whereas no change in secondary structure was
      detected by circular dichroism. The thiol-blocking agent N-ethylmaleimide was
      applied in order to inhibit formation of disulfide bonds during gel formation.
      Results showed that increased contents of alpha-lactalbumin (alpha-La) were
      associated with increased sensitivity to ultrasonication. The alpha-La:beta
      lactoglobulin (beta-Lg) ratio greatly affected the nature of the interactions
      formed during gelation, where higher amounts of alpha-La lead to a gel more
      dependent on disulfide bonds. These results contribute to clarifying the
      mechanisms mediating the effects of HIU on whey proteins on the molecular level,
      thus moving further toward implementing HIU in the processing chain in the food
      industry.

PMID- 26304369
TI  - Simultaneous spectrophotometric determination of copper, cobalt, nickel and iron
      in foodstuffs and vegetables with a new bis thiosemicarbazone ligand using
      chemometric approaches.
AB  - A newly synthesized bis thiosemicarbazone ligand, (2Z,2'Z)-2,2'-((4S,5R)-4,5,6
      trihydroxyhexane-1,2-diylidene)bis(N-phenylhydrazinecarbothioamide), was used to
      make a complex with Cu(2+), Ni(2+), Co(2+) and Fe(3+) for their simultaneous
      spectrophotometric determination using chemometric methods. By Job's method, the
      ratio of metal to ligand in Ni(2+) was found to be 1:2, whereas it was 1:4 for
      the others. The effect of pH on the sensitivity and selectivity of the formed
      complexes was studied according to the net analyte signal (NAS). Under optimum
      conditions, the calibration graphs were linear in the ranges of 0.10-3.83, 0.20
      3.83, 0.23-5.23 and 0.32-8.12 mg L(-1) with the detection limits of 2, 3, 4 and
      10 MUg L(-1) for Cu(2+), Co(2+), Ni(2+) and Fe(3+) respectively. The OSC-PLS1 for
      Cu(2+) and Ni(2+), the PLS1 for Co(2+) and the PC-FFANN for Fe(3+) were selected
      as the best models. The selected models were successfully applied for the
      simultaneous determination of elements in some foodstuffs and vegetables.

PMID- 26304370
TI  - Development of multi-residue analysis of herbicides in cereal grain by ultra
      performance liquid chromatography-electrospray ionization-mass spectrometry.
AB  - A rapid and sensitive method was developed for the determination of 50 herbicides
      in cereal grain by ultra-performance liquid chromatography-electrospray
      ionization-mass spectrometry (UPLC-ESI-MS). Using acetonitrile effectively
      extracted 22 kinds of triazine and other basic herbicides, and using 90:10 v/v
      acetonitrile-phosphate buffer (pH = 7.5) effectively extracted other 28
      herbicides. Chromatographic separation was achieved using gradient elution with
      acetonitrile-water as a mobile phase for 22 triazine and phenylurea herbicides
      and with 5mM ammonium acetate aqueous solution containing 0.1% formic acid
      acetonitrile as a mobile phase for other 28 herbicides. Using matrix-matched
      standard calibration curve effectively reduced the indirect matrix effects,
      ensured accurate quantification for these herbicides. The response was linear
      over two orders of magnitude with a correlation coefficients (r(2)) higher than
      0.992. The limits of quantification for the herbicides varied from 0.2 to 25.6
      MUg kg(-1). The intra- and inter-day precisions (relative standard deviation,
      RSD) were 2.2-9.3% and 5.7-17.1%, respectively. The recovery varied from 61.6% to
      110% with the RSD of 1.6-11.8%. Analyzing soybean, corn and wheat samples from 17
      counties evaluated this method. The developed and validated method has high
      sensitivity, satisfactory recovery and precision, can ensure the multi-class
      multi-residue analysis at low MUg kg(-1) level for the most herbicides in cereal
      grain.

PMID- 26304371
TI  - A screening method of oil-soluble synthetic dyes in chilli products based on
      multi-wavelength chromatographic fingerprints comparison.
AB  - A multi-wavelength HPLC fingerprint comparison method was proposed for the
      screening of oil-soluble synthetic dyes in chilli products. The screening was
      based on the fingerprint differences of normal unadulterated chilli sample with
      tested chilli samples. The samples were extracted with acetone and fingerprinted
      by HPLC under four visible light wavelengths (450 nm, 490 nm, 520 nm, and 620
      nm). It was found that the fingerprints of different chilli product samples had a
      relatively fixed number of peaks and stable retention time. When 16 kinds of
      known synthetic dyes were used as model analytes to assess the screening
      efficiency, 14 of them could be screened using fingerprint comparison method,
      with LOD of 0.40-2.41 mg/kg. The new screening method was simple and had the
      possibility of finding existence of the adulterated dyes which could not be
      identified using known standard analytes as control.

PMID- 26304372
TI  - Pressurized liquid extraction of phenolic compounds from rice (Oryza sativa)
      grains.
AB  - An analytical pressurized liquid extraction (PLE) process has been studied for
      the extraction of phenolic compounds from rice grains. A fractional factorial
      design (2(7-2)) with a centre point was used to optimize PLE parameters such as
      solvent composition (EtOAc in MeOH), extraction temperature, pressure, flushing,
      static extraction time, solvent-purge and sample weight. Extraction temperature,
      solvent and static extraction time were found to have a significant effect on the
      response value. The optimized method was validated for selectivity, linearity,
      limits of detection and quantification, recovery and precision. The validated
      method was successfully applied for the analysis of a wide variety of rice
      grains. Seventeen phenolic compounds were detected in the sample and guaiacol,
      ellagic acid, vanillic acid and protocatechuic acid were identified as the most
      abundant compounds. Nonetheless, different species of rice show very varied
      compound diversity and levels of compounds in their grain compositions. 

PMID- 26304373
TI  - The challenging SO2-mediated chemical build-up of protein aggregates in wines.
AB  - Despite the extensive research performed during the last decades, the
      multifactorial mechanism responsible for white wine protein haze formation is not
      fully characterized. A model is proposed, which is essentially based on two
      postulates: the experimental identification of sulfur dioxide as the non
      proteinaceous factor, and the inference from reliable data available in the
      literature of the dynamic chemistry played by wine protein sulfhydryl groups.
      Unlike other reducing agents, addition of SO2 to must/wine upon heating cleaves
      intraprotein disulfide bonds, hinders thiol-disulfide exchange during protein
      interactions, and leads to formation of novel interprotein disulfide bonds. These
      bonds are ultimately responsible for wine protein aggregation following a
      nucleation-growth kinetic model, as shown by Dynamic Light Scattering
      experiments. The model was tested in wine model solution (using total and
      fractionated wine proteins) and validated under real wine conditions. The results
      achieved may open the way to develop techniques that will find wide application
      in the wine industry. 

PMID- 26304374
TI  - Improving the sweet aftertaste of green tea infusion with tannase.
AB  - The present study aims to improve the sweet aftertaste and overall acceptability
      of green tea infusion by hydrolyzing (-)-epigallocatechin gallate (EGCG) and (-)
      epicatechin gallate (ECG) with tannase. The results showed that the intensity of
      the sweet aftertaste and the score of overall acceptability of the green tea
      infusion significantly increased with the extension of the hydrolyzing treatment.
      (-)-Epigallocatechin (EGC) and (-)-epicatechin (EC) were found to be the main
      contributors for the sweet aftertaste, based on a trial compatibility with EGCG,
      ECG, EGC, and EC monomers, and a synergistic action between EGC and EC to sweet
      aftertaste was observed. A 2.5:1 (EGC/EC) ratio with a total concentration of 3.5
      mmol/L gave the most satisfying sweet aftertaste, and the astringency
      significantly inhibited the development of the sweet aftertaste. These results
      can help us to produce a tea beverage with excellent sweet aftertaste by
      hydrolyzing the green tea infusion with tannase.

PMID- 26304375
TI  - Improving the prediction ability of FT-MIR spectroscopy to assess titratable
      acidity in cow's milk.
AB  - This study investigated the potential application of Fourier transform mid
      infrared spectroscopy (FT-MIR) for the determination of titratable acidity (TA)
      in cow's milk. The prediction model was developed on 201 samples collected from
      cows in early and late lactation, and was successively used to predict TA on
      samples collected from cows in early lactation and in samples with high somatic
      cell count. The root mean square error of cross-validation of the model by using
      external validation dataset was 0.09  degrees Soxhlet-Henkel/50 mL. Applying the
      model on milk samples from cows in early lactation or with high somatic cell
      count, the root mean square error of prediction was 0.163  degrees Soxhlet
      Henkel/50 mL, with a RER and RPD of 23.9 and 5.1, respectively. Our results seem
      to indicate that FT-MIR can be used in individual milk samples to accurately
      predict TA, and has the potential to be adopted to measure routinely the TA of
      milk.

PMID- 26304376
TI  - Detection of adulterated murine components in meat products by TaqMan(c) real
      time PCR.
AB  - Using murine meat to substitute mutton has been identified as a new type of meat
      fraud in China, yet no detection method for murine species has been reported.
      Here, three kinds of rodent were used as target species to establish a murine
      specific real-time PCR method of detection. The mitochondrial cytochrome b gene
      (cytb) of each target was sequenced and a TaqMan probe was designed based on the
      cytb. Simultaneously, an internal positive control (IPC) plasmid along with its
      respective probe were designed to monitor the PCR reaction. As a result, the
      duplex real-time PCR system was verified to be specific. The limit of detection
      (LOD) was lower than 1 pg of DNA per reaction and 0.1% murine contamination in
      meat mixtures. Standard curves were generated for a quantitative analysis. Thus,
      this study provided a new tool to control the quality of meat products for
      official and third-party laboratories.

PMID- 26304377
TI  - Evaluation of protease resistance and toxicity of amyloid-like food fibrils from
      whey, soy, kidney bean, and egg white.
AB  - The structural properties of amyloid fibrils combined with their highly
      functional surface chemistry make them an attractive new food ingredient, for
      example as highly effective gelling agents. However, the toxic role of amyloid
      fibrils in disease may cause some concern about their food safety because it has
      not been established unequivocally if consumption of food fibrils poses a health
      risk to consumers. Here we present a study of amyloid-like fibrils from whey,
      kidney bean, soy bean, and egg white to partially address this concern. Fibrils
      showed varied resistance to proteolytic digestion in vitro by either Proteinase
      K, pepsin or pancreatin. The toxicity of mature fibrils was measured in vitro and
      compared to native protein, early-stage-fibrillar protein, and sonicated fibrils
      in two immortalised human cancer cell lines, Caco-2 and Hec-1a. There was no
      reduction in the viability of either Caco-2 or Hec-1a cells after treatment with
      a fibril concentration of up to 0.25 mg/mL.

PMID- 26304378
TI  - Study on chemical profiles and metabolites of Allii Macrostemonis Bulbus as well
      as its representative steroidal saponins in rats by ultra-performance liquid
      chromatography coupled with quadrupole time-of-flight tandem mass spectrometry.
AB  - Allii Macrostemonis Bulbus (AMB) is increasingly becoming popular as an edible
      vegetable or traditional folk medicine in East Asia due to its great health and
      medicinal properties. However, due to a lack of available research, the effective
      material of AMB still remains unknown. In this study, we applied a strategy
      utilising ultra-performance liquid chromatography coupled with quadrupole time-of
      flight tandem mass spectrometry (UPLC/Q-TOF-MS) to investigate chemical profiles
      of AMB. In addition, metabolite profiles of five representative single steroidal
      saponins as well as AMB were investigated. Moreover, the metabolic features of
      saponins in AMB were summarised. After oral administration, the saponins
      underwent massive phase I and phase II metabolism. Sequential deglycosylation
      metabolism in rat intestine was the main metabolic pathway of the steroidal
      saponins, while oxidation, dehydrogenation, glucuronic acid reactions in liver
      also take part in further modification. These results expand our knowledge about
      the metabolism of AMB. 

PMID- 26304379
TI  - Changes in the color, chemical stability and antioxidant capacity of thermally
      treated anthocyanin aqueous solution over storage.
AB  - Many anthocyanin-containing foods are thermally processed to ensure their safety,
      and stored for some time before being consumed. However, the combination of
      thermal processing and subsequent storage has a significant impact on
      anthocyanins. This study aimed to investigate the color, chemical stability, and
      antioxidant capacity of thermally treated anthocyanin aqueous solutions during
      storage at 4, 25, 45, and 65  degrees C, respectively. Anthocyanin aqueous
      solutions were thermally treated before storage. Results showed that the
      degradation rate of anthocyanins in aqueous solutions was much faster than those
      in real food. The color of the anthocyanin aqueous solutions changed dramatically
      during storage. The anthocyanin aqueous solutions stored at 4  degrees C showed
      the best chemical stability. Interestingly, the antioxidant capacity of the
      anthocyanin aqueous solutions stored at lower temperatures remained the same;
      however, the antioxidant capacity of those thermally treated at 120 or 140 
      degrees C and stored at 45 or 65  degrees C significantly decreased.

PMID- 26304380
TI  - Dual-labeled time-resolved fluoroimmunoassay for simultaneous detection of
      clothianidin and diniconazole in agricultural samples.
AB  - Europium (Eu(3+)) and samarium (Sm(3+)) were used as fluorescent labels to
      develop a highly sensitive dual-labeled time-resolved fluoroimmunoassay (TRFIA)
      for detect clothianidin and diniconazole in food samples. Under the optimized
      assay conditions, 50% inhibition concentration (IC50) and the limit of detection
      (LOD, IC10) of clothianidin were 5.08 and 0.021 MUg/L, and 13.14 and 0.029 MUg/L
      for diniconazole. The cross-reactivities (CRs) were negligible except dinotefuran
      (9.4%) and uniconazole (4.28%). The recoveries of clothianidin and diniconazole
      ranged from 79.3% to 108.7% in food samples. The results of TRFIA for the
      authentic samples were validated by gas chromatography (GC) analyses, and a
      satisfactory correlations were obtained. These results indicated that the method
      was an alternative tool for simultaneous detection of clothianidin and
      diniconazole in food samples.

PMID- 26304381
TI  - Global metabolite profiling and diagnostic ion filtering strategy by LC-QTOF MS
      for rapid identification of raw and processed pieces of Rheum palmatum L.
AB  - Due to its variety of functions, rhubarb has been used for thousands of years in
      many countries. It is commonly used after processing. Processing usually affect
      the chemical profile and the contents of active compounds in herbals, leading to
      changes of their bioactivities. Here, an approach of metabolite profiling and
      diagnostic ion filtering strategy with liquid chromatography-quadrupole/time-of
      flight mass spectrometry was established for rapid identification of raw and
      processed pieces of Rheum palmatum L. (RPL). The comprehensive and unbiased
      information of 30 batches of RPL covering raw and two general processing methods
      were given by metabolomic profiles. Using molecular feature extraction algorithm,
      non-targeted compounds were analyzed in minutes. In total, 73 characteristic
      markers were extracted and identified by diagnostic ion filtering. They have been
      further analyzed by partial least squares-support vector machine-based pattern
      recognition. The comprehensive and rapid method for raw and processed pieces of
      RPL classification shows good sensitivity, specificity and prediction
      performance. 

PMID- 26304382
TI  - Integrated utilization of red radish seeds for the efficient production of seed
      oil and sulforaphene.
AB  - Supercritical CO2 was used to obtain seed oil from red radish seeds. The
      influence of pressure, temperature, CO2 flow rate and time on extraction yield of
      oil were investigated in detail. The maximum extraction yield of oil was 92.07 +/
      0.76% at the optimal extraction conditions. The physicochemical properties and
      fatty acid composition of oil indicated that the seed oil can be used as a
      dietary oil. Meanwhile, the high purity sulforaphene (96.84 +/- 0.17%) was
      separated by solvent extraction coupled with preparative high performance liquid
      chromatography from red radish seed meal. The initial pH, R, extraction
      temperature and extraction time for each cycle had a considerable influence both
      on the extraction yield and purity of sulforaphene of crude product. The
      extraction of oil was directly responsible for an increase of 18.32% in the yield
      of sulforaphene.

PMID- 26304383
TI  - Orthogonal projection approach and continuous wavelet transform-feed forward
      neural networks for simultaneous spectrophotometric determination of some heavy
      metals in diet samples.
AB  - Simultaneous spectrophotometric determination of a mixture of overlapped
      complexes of Fe(3+), Mn(2+), Cu(2+), and Zn(2+) ions with 2-(3-hydroxy-1-phenyl
      but-2-enylideneamino) pyridine-3-ol(HPEP) by orthogonal projection approach-feed
      forward neural network (OPA-FFNN) and continuous wavelet transform-feed forward
      neural network (CWT-FFNN) is discussed. Ionic complexes HPEP were formulated with
      varying reagent concentration, pH and time of color formation for completion of
      complexation reactions. It was found that, at 5.0 * 10(-4) mol L(-1) of HPEP, pH
      9.5 and 10 min after mixing the complexation reactions were completed. The
      spectral data were analyzed using partial response plots, and identified non
      linearity modeled using FFNN. Reducing the number of OPA-FFNN and CWT-FFNN inputs
      were simplified using dissimilarity pure spectra of OPA and selected wavelet
      coefficients. Once the pure dissimilarity plots ad optimal wavelet coefficients
      are selected, different ANN models were employed for the calculation of the final
      calibration models. The performance of these two approaches were tested with
      regard to root mean square errors of prediction (RMSE %) values, using synthetic
      solutions. Under the working conditions, the proposed methods were successfully
      applied to the simultaneous determination of metal ions in different vegetable
      and foodstuff samples. The results show that, OPA-FFNN and CWT-FFNN were
      effective in simultaneously determining Fe(3+), Mn(2+), Cu(2+), and Zn(2+)
      concentration. Also, concentrations of metal ions in the samples were determined
      by flame atomic absorption spectrometry (FAAS). The amounts of metal ions
      obtained by the proposed methods were in good agreement with those obtained by
      FAAS.

PMID- 26304384
TI  - A novel chemo-enzymatic synthesis of hydrophilic phytosterol derivatives.
AB  - In this study, a novel method was developed for chemo-enzymatic synthesis of
      hydrophilic phytosterol derivatives, phytosteryl polyethylene glycol succinate
      (PPGS), through an intermediate phytosteryl hemisuccinate (PSHS), which was first
      chemically prepared and subsequently coupled with polyethylene glycol (PEG)
      through lipase-catalyzed esterification. The chemical structure of intermediate
      and goal product were finally confirmed to be PSHS and PPGS by FT-IR, MS and NMR,
      suggesting that hydrophilic phytosterol derivatives were successfully
      synthesized. The effects of various parameters on the conversion of PSHS to PPGS
      were investigated and the highest conversion (>78%) was obtained under the
      selected conditions: 75 mmol/L PSHS, 1:2M ratio of PSHS to PEG, 50 g/L Novozym
      435, 120 g/L 3 A molecular sieves in tert-butanol, 55  degrees C, 96 h and 200
      rpm. The solubility of phytosterols in water was significantly improved by
      coupling with PEG, facilitating the incorporation into a variety of foods
      containing water.

PMID- 26304385
TI  - Development and validation of a liquid chromatography method for anthocyanins in
      strawberry (Fragaria spp.) and complementary studies on stability, kinetics and
      antioxidant power.
AB  - A RPLC-DAD method for the analysis of eight anthocyanins was developed, validated
      and applied to strawberry extracts. The chromatographic method was conducted
      under gradient elution in acidulated water-methanol mobile phase and octadecyl
      silica columns. An ultrasound extraction procedure was optimized by a 3(2)
      factorial design (%HCl in methanol, temperature, and time) and response surface
      methodology. Method validation was performed according to the following
      parameters: linearity (R(2)>0.99, p-value<10(-4), F>725), LOD (3-7 MUmol L(-1))
      and LOQ (9-22 MUmol L(-1)), selectivity/specificity (baseline separation of all
      analytes and peak purity), instrumental precision (<6.4%CV), repeatability
      (<6.3%CV) and intermediate precision (<9.9%CV), recovery (83-99%), robustness
      (mobile phase pH, column temperature and flow rate) and stability (high
      temperatures and storage; 1st order kinetics). The antioxidant power of
      anthocyanins was measured on-line (ABTS(+) reaction; Trolox as reference). Ten
      strawberry extracts were quantified (average values: 24.2 MUg/g for cyanidin-3
      glucoside and 49.1 MUg/g for pelargonidin-3-glucoside).

PMID- 26304386
TI  - Acrylamide and 5-hydroxymethylfurfural formation during baking of biscuits: Part
      I: Effects of sugar type.
AB  - This study aimed to investigate the effects of sugar type on the reaction
      mechanism for formation of acrylamide and 5-hydroxymethylfurfural (HMF) during
      the baking of biscuits at 200 degrees C using multiresponse modelling. Four types
      of biscuits were prepared: (1) with sucrose, (2) with glucose and fructose, (3)
      with fructose only and (4) with glucose only. Experimental data showed that HMF
      concentration was highest in biscuits with glucose and fructose, whereas
      acrylamide concentration was highest in biscuits with glucose, also having the
      highest asparagine concentration. Proposed mechanistic models suggested that HMF
      is formed via caramelisation and that acrylamide formation follows the specific
      amino acid route, i.e., reducing sugars react with asparagine to form the Schiff
      base before decarboxylation, to generate acrylamide without the Amadori
      rearrangement product and sugar fragmentation. Study results contribute to
      understanding chemical reaction pathways in real food products. 

PMID- 26304387
TI  - Non-additive response of blends of rice and potato starch during heating at
      intermediate water contents: A differential scanning calorimetry and proton
      nuclear magnetic resonance study.
AB  - The impact of different hydration levels, on gelatinization of potato starch
      (PS), rice starch (RS) and a 1:1 blend thereof, was investigated by differential
      scanning calorimetry and related to nuclear magnetic resonance proton
      distributions of hydrated samples, before and after heating. At 20% or 30%
      hydration, the visual appearance of all samples was that of a wet powder, and
      limited, if any, gelatinization occurred upon heating. At 30% hydration, changes
      in proton distributions were observed and related to plasticization of amorphous
      regions in the granules. At 50% hydration, the PS-RS blend appeared more liquid
      like than other hydrated samples and showed more pronounced gelatinization than
      expected based on additive behavior of pure starches. This was due to an
      additional mobile water fraction in the unheated PS-RS blend, originating from
      differences in water distribution due to altered stacking of granules and/or
      altered hydration of PS due to presence of cations in RS. 

PMID- 26304388
TI  - Dynamic microwave-assisted extraction combined with continuous-flow
      microextraction for determination of pesticides in vegetables.
AB  - A simple, rapid, solventless and cost-effective dynamic microwave-assisted
      extraction (DMAE) combined with continuous-flow microextraction (CFME) system was
      firstly assembled and validated for extraction of eight organophosphorus
      pesticides in vegetables. The method combines the advantages of DMAE and CFME,
      and extends the application of the single drop microextraction to complex solid
      samples. The extraction, separation, and enrichment were performed in a single
      step, which could greatly simplify the operation and reduce the whole
      pretreatment time. In the developed method, analytes were first extracted from
      the vegetables using 3% NaCl solution as extraction solvent, then concentrated
      into microextraction solvent. After extraction, the microextraction solvent
      containing the enriched analyte was directly analyzed by GC-MS without any
      filtration or clean-up process. Several parameters affecting the extraction
      efficiency were investigated and optimized. Real vegetable samples were analyzed,
      satisfactory recoveries were obtained in the range of 80.7-106.7%, and relative
      standard deviations were lower than 8.7%. 

PMID- 26304389
TI  - Characterisation of volatile profile and sensory analysis of fresh-cut "Radicchio
      di Chioggia" stored in air or modified atmosphere.
AB  - The volatile profile of two hybrids of "Radicchio di Chioggia", Corelli and
      Botticelli, stored in air or passive modified atmosphere (MAP) during 12 days of
      cold storage, was monitored by solid phase micro-extraction (SPME) GC-MS.
      Botticelli samples were also subjected to sensory analysis. Totally, 61 volatile
      organic compounds (VOCs) were identified in the headspace of radicchio samples.
      Principal component analysis (PCA) showed that fresh product possessed a
      metabolic content similar to that of the MAP samples after 5 and 8 days of
      storage. Projection to latent structures by partial least squares (PLS)
      regression analysis showed the volatiles content of the samples varied depending
      only on the packaging conditions. Specifically, 12 metabolites describing the
      time evolution and explaining the effects of the different storage conditions
      were highlighted. Finally, a PCA analysis revealed that VOCs profile
      significantly correlated with sensory attributes.

PMID- 26304390
TI  - Determination of nitrofurans metabolites residues in aquatic products by ultra
      performance liquid chromatography-tandem mass spectrometry.
AB  - A method was described for monitoring four nitrofuran metabolites including 5
      methylmorpholino-3-amino-2-oxazolidinone (AMOZ), 3-amino-2-oxazolidone (AOZ), 1
      amino-hydantoin (AHD) and semicarbazide (SEM) in aquatic products. The analytes
      were quantified by ultra-performance liquid chromatography-tandem mass
      spectrometry operating in positive ion multiple monitoring mode (MRM) after 2
      nitrobenzaldehyde derivatization. The matrix calibration curve was established
      with correlation coefficient (R(2)>0.99) in the range of 1-100 ng ml(-1). Limit
      of detection and limit of quantification for all analytes were 0.5 and 1.5 MUg
      kg(-1), respectively. Recovery rates and relative standard deviations ranged from
      88% to 112% and 2% to 4%, respectively. The validated method was successfully
      applied to detect nitrofuran metabolites in 120 fish samples. The analytes were
      detected in 6/16 species of fish samples, with a total detection rate of 6.5%.
      AOZ was most frequently detected (8.3%), followed by AMOZ (7.5%), AHD (5.0%) and
      SEM (5.0%). The method is proposed for monitoring nitrofuran metabolites in
      aquatic products.

PMID- 26304391
TI  - Metabolomics and microbiological profile of Italian mozzarella cheese produced
      with buffalo and cow milk.
AB  - Italian buffalo mozzarella (BM) cheese metabolite profile and microbial
      communities were characterised and compared to cow mozzarella (CM). Polar
      metabolite profiles were studied by gas-chromatography mass-spectrometry (GC-MS)
      and results elaborated by multivariate analysis (MVA). BM produced using natural
      whey starter cultures (NWS) exhibited a higher microbial diversity with less
      psychrotrophic bacteria. BM samples were higher in threonine, serine, valine, and
      lower in orotic acid and urea. CM produced with commercial starters (CMS) had the
      highest count of Streptococcus thermophilus and higher levels of galactose and
      phenylalanine. CM obtained by direct acidification (CMA) had lower microbial
      counts and higher levels of urea and sugars. Orotic acid was the only metabolite
      linked to milk animal origin. Results indicated that this metabolite pool well
      reflects the different production protocols and microbial complexity of these
      dairy products. This approach can help to protect the designation of origin of
      Italian buffalo mozzarella. 

PMID- 26304392
TI  - Potentially bioaccessible phenolics, antioxidant activity and nutritional quality
      of young buckwheat sprouts affected by elicitation and elicitation supported by
      phenylpropanoid pathway precursor feeding.
AB  - This paper presents the study on impact of elicitation and the phenylpropanoid
      pathway feeding on the nutritional quality, the potentially bioaccessible
      phenolics and the antioxidant capacity of young buckwheat sprouts. Phenolics
      content was increased by elicitation and feeding with tyrosine and shikimic acid-
      an elevation of 30% and 17%, respectively. Antioxidant capacity was improved by
      feeding with tyrosine--an increase of 16.7% and 17.1% in both untreated and
      treated sprouts, respectively. The highest protein digestibility was determined
      for the control sprouts and those obtained after tyrosine feeding. The lowest
      starch digestibility was found for elicited sprouts obtained from seeds fed with
      tyrosine (a decrease by 52%). An increase of expected glycemic index by 38% was
      determined for elicited sprouts obtained after phenylalanine feeding. Starch and
      protein digestibility were negatively correlated with total phenolics (r = -0.55
      and -0.58, respectively), however starch digestibility was also affected by
      resistant starch content.

PMID- 26304393
TI  - Development of C13-norisoprenoids, carotenoids and other volatile compounds in
      Vitis vinifera L. Cv. Pinot noir grapes.
AB  - Developmental changes in the carotenoids and volatile compounds of Pinot noir
      grape berries were investigated in this study from pea size to harvest during
      2012. HPLC analysis showed continued decrease of lutein, beta-carotene, neochrome
      a and neoxanthin continued to decrease during berry development, with rapid
      decrease of lutein and (9'z)-neoxanthin occurred two weeks before veraison.
      Neochrome b and violaxanthin accumulated at early development and started to
      decrease two weeks before veraison. Volatile analysis demonstrated that total
      beta-damascenone, TDN and vitispirane all increased dramatically, especially at
      later stage of ripening, whereas the changes for alpha-ionone and beta-ionone
      were not obvious. The correlation between carotenoids and C13-norisoprenoids in
      the grape berries was compound-dependent, suggesting dependency on enzyme
      activity and specificity. In addition, C6-alcohols accumulated before veraison
      and decreased towards maturation, and 3-isobutyl-2-methoxyprazine decreased with
      increasing maturity. 

PMID- 26304394
TI  - Detection of bacterial concentration variations based on dielectric magnetic
      flux.
AB  - This study is based on the development of bacterial count quantification
      generated by medium dielectric variations and consequent polarization material
      release. The proposed approach is an action method for the fast detection of
      bacterial concentration in orange juice. The sensing method relies on bacterial
      attachment up to biofilm formation. Furthermore, different media provide more
      oxygen group content to enhance capacitance and self-discharge. The test took
      only 30 min and it provided the means for rapid bacterial detection in the juice
      industry.

PMID- 26304395
TI  - Supercritical extraction of sunflower oil: A central composite design for
      extraction variables.
AB  - Supercritical carbon dioxide (SC-CO2) extraction of sunflower seed for the
      production of vegetable oil is investigated and compared to conventional methods.
      The effects of extracting variables, namely pressure, temperatures, particle
      size, SC-CO2 flow rate and co-solvent, on SC-CO2 extraction are investigated. The
      maximum yield for sunflower oil is found to be about 54.37 wt%, and is obtained
      when SC-CO2 extraction is carried out at 80  degrees C, 400 bar, 0.75 mm particle
      and 10 g/min solvent flow with 5% co-solvent. A central composite design is used
      to develop the model and also to predict the optimum conditions. At optimum
      conditions obtained based on desirability function, 80.54  degrees C, 345 bar,
      1.00 mm, 10.50 g/min and 7.58% ethanol, SC-CO2 extraction has performed and found
      that extraction yield dropped by 2.88% from the predicted value. Fatty acid
      composition of SC-CO2 and hexane extracted oil shows negligible difference and
      found high source of linoleic acid.

PMID- 26304396
TI  - The influence of cheese composition and microstructure on the diffusion of
      macromolecules: A study using Fluorescence Recovery After Photobleaching (FRAP).
AB  - In cheese technology, the diffusion phenomena are crucial during ripening. The
      technique of Fluorescence Recovery After Photobleaching was applied for the first
      time on real cheese, in order to investigate the relationships between molecular
      diffusion and the cheese composition and/or its microstructure. Measured
      effective diffusion coefficients in soft and hard cheese of a group of dextrans
      (10-500 kDa) were found to be in the same order of magnitude with values observed
      when using a comparable non-fat model cheese (~ 0.1-20 MUm(2) s(-1)). Diffusion
      of the dextrans was mainly dependent on the fraction of "free" aqueous phase
      present in the cheese, closely which is linked to cheese-making technology and
      ripening stage. Diffusion coefficients were modeled by a power law relationship
      as a function of dextran molecular weight, which allowed some study of the cheese
      microstructure. A tighter protein network will require some deformation of those
      flexible macromolecules with a higher molecular weight (>250 kDa), in order to
      diffuse through the pores of such cheese structures.

PMID- 26304397
TI  - Miniaturisation and optimisation of the Dutch mini-Luke extraction method for
      implementation in the routine multi-residue analysis of pesticides in fruits and
      vegetables.
AB  - This paper presents the validation and further miniaturisation of the well-known
      Dutch mini-Luke method for high water and acid content matrices for 175
      pesticides amenable to liquid- and gas chromatography-mass spectrometry. For
      optimisation of the method, recovery tests with different sample/extraction
      solvent ratios, varying amounts of dichloromethane and salts were performed with
      fifty representative pesticides. Solvent consumption could be reduced
      considerably, especially for the dichloromethane (by a factor of 3). Recovery
      studies performed with lettuce and orange matrix spiked at 0.005, 0.01 and 0.02
      mg/kg yielded average recoveries in the range 70-120% with relative standard
      deviation values below 20% for almost all the pesticides tested. The linearity
      over three orders of magnitude was demonstrated (r(2) > 0.99). The matrix effect
      could be considered as not significant. The limit of quantification was 0.005
      mg/kg for 96% of the compounds. The optimised New Dutch mini-Luke ("NL"-) method
      was applied successfully in routine analysis and the EUPT FV-16 sample.

PMID- 26304398
TI  - Production of long chain omega-3 fatty acids and carotenoids in tropical areas by
      a new heat-tolerant microalga Tetraselmis sp. DS3.
AB  - Demand for long chain omega-3 fatty acids from non-fish source for vegetarians
      has increased recently. Marine microalgae are the primary producers of EPA/DHA
      and promising alternatives for fish oil. Tropical areas have abundant sunlight
      throughout the year for microalgal cultivation but this practice can be hindered
      by high temperature. Discovery of heat-tolerant marine microalgae that can
      synthesize EPA/DHA will solve these problems. A new species of microalga was
      isolated from a high temperature lagoon and identified as Tetraselmis sp. DS3.
      These cells could grow at 40  degrees C, the highest temperature for marine
      microalgal growth ever reported. Its omega-3 fatty acids and EPA accounted for 33
      and 10% of total lipids, respectively, grown in nitrogen-depleted conditions.
      These cells also accumulated more than 5% beta-carotene and 0.48% lutein in
      biomass. This new microalga can be cultivated for long chain omega-3 fatty acids
      and lutein production in the tropical areas.

PMID- 26304399
TI  - Batch-injection analysis with amperometric detection of the DPPH radical for
      evaluation of antioxidant capacity.
AB  - This work proposes the application of batch-injection analysis with amperometric
      detection to determine the antioxidant capacity of real samples based on the
      measurement of DPPH radical consumption. The efficient concentration or EC50
      value corresponds to the concentration of sample or standard required to scavenge
      50% DPPH radicals. For the accurate determination of EC50, samples were incubated
      with DPPH radical for 1h because many polyphenolic compounds typically found in
      plants and responsible for the antioxidant activity exhibit slow kinetics. The
      BIA system with amperometric detection using a glassy-carbon electrode presented
      high precision (RSD = 0.7%, n = 12), low detection limit (1 MUmol L(-1)) and
      selective detection of DPPH (free of interferences from antioxidants). These
      contributed to low detection limits for the antioxidant (0.015 and 0.19 MUmol L(
      1) for gallic acid and butylated hydroxytoluene, respectively). Moreover, BIA
      methods show great promise for portable analysis because battery-powered
      instrumentation (electronic micropipette and potentiostats) is commercially
      available.

PMID- 26304400
TI  - Identification and quantification of phenolics in Australian native mint (Mentha
      australis R. Br.).
AB  - Australian native mints have traditionally been used by the aboriginal people for
      natural remedies; however, their bioactive components have not been studied.
      Antioxidant capacity and composition of phenolic compounds of Mentha australis R.
      Br., Lamiaceae were investigated for the first time. Phenolic compounds were
      analyzed by HPLC photodiode array detector, liquid chromatography high resolution
      mass spectrometry, tandem mass spectrometry and nuclear magnetic resonance
      spectroscopy. Aqueous methanolic extract of the mint exhibited comparable
      antioxidant capacity to the common spearmint. Major compounds identified in the
      extract were rosmarinic acid (160.4 +/- 0.85 MUg mg(-1)purified extract),
      neoponcirin (145.0 +/- 0.42 MUg gallic acid equivalent(GAE) mg(-1)), narirutin
      (30.3 +/- 0.02 MUg GAE mg(-1)), chlorogenic acid (15.4 +/- 0.05 MUg mg(-1)) and
      biochanin A (9.6 +/- 0.06 MUg GAE mg(-1)), while minor compounds were caffeic
      acid, apigenin, hesperetin and naringenin. Neoponcirin and biochanin A were
      identified for the first time in the Mentha genus.

PMID- 26304401
TI  - Partial purification and characterisation of the peptide precursors of the cocoa
      specific aroma components.
AB  - Essential precursors of the cocoa-specific aroma notes are formed during
      fermentation of the cocoa beans by acid-induced proteolysis. It has been shown
      that, in addition to free amino acids, hydrophilic peptides derived from the
      vicilin-class(7S) globular storage protein are required for the generation of the
      cocoa-specific aroma notes during the roasting process. To identify those
      peptides responsible for the generation of the cocoa-specific aroma components,
      we have developed a procedure for the fractionation of the aroma precursor
      extract from well-fermented cocoa beans by ligand-exchange and subsequent
      Sephadex-LH20 chromatography. The cocoa-specific aroma precursor fractions were
      characterised by matrix-assisted laser-desorption/ionisation time-of-flight mass
      spectrometry (MALDI-TOF) and the determination of their amino acid sequences by
      electrospray ionisation mass spectrometry (ESI-MS/MS). 

PMID- 26304402
TI  - Carotenoid evolution during short-storage period of durum wheat (Triticum
      turgidum conv. durum) and tritordeum (*Tritordeum Ascherson et Graebner) whole
      grain flours.
AB  - This study investigates the effect of storage temperature on carotenoid
      composition in durum wheat and tritordeum whole-grain flours. For both cereal
      genotypes, total carotenoid content significantly decreased during storage,
      following a temperature dependent first-order kinetic model. Individual and total
      carotenoid content decay were similar for durum wheat, with a maximum at 50 
      degrees C at the end of the storage period (94%). In contrast, the evolution of
      lutein ester fractions in tritordeum showed lower losses than for free lutein (~
      50%), and consequently the total carotenoid content was less affected (83%). A
      decrease in the lutein monoesters fraction was observed, coinciding with an
      increase in the diesterified forms, especially for lutein dilinoleate. These data
      suggest an esterifying activity in flours different from the enzyme systems
      operating in vivo (xanthophyll acyl transferase). The formation of lutein
      diesters, with greater stability, explains the slower carotenoid degradation in
      tritordeum whole-grain flours.

PMID- 26304403
TI  - Phytosterols in onion contribute to a sensation of lingering of aroma, a koku
      attribute.
AB  - We aimed to examine the substance in a precipitate of heat-treated onion
      concentrate (HOC) that contributes to a sensation of lingering of aroma, a koku
      attribute induced by the sensing of richness and persistence in terms of taste,
      aroma and texture. Adding precipitate, separated from HOC, to consomme enhanced
      the lingering sensation of aroma in the consomme more than adding the supernatant
      from HOC. After the precipitate was washed with hot water and ethanol its
      enhancing effect disappeared. Analysis of the HOC precipitate showed that it
      contained phytosterols, such as beta-sitosterol and stigmasterol. Tests of
      binding to aroma compounds showed that both sterols, as well as the washed
      precipitate, were able to bind methyl propyl disulfide and N-hexanal. Thus
      phytosterols in the HOC precipitate seemed to bind and hold the aroma compounds
      and gradually release them, inducing a lingering sensation of aroma under the
      koku concept during consumption. 

PMID- 26304404
TI  - Physicochemical and in vitro binding properties of barley beta-glucan treated
      with hydrogen peroxide.
AB  - This study investigated the changes in content, purity, physical properties, and
      in vitro binding properties of barley beta-glucan by oxidation treatment. Barleys
      (Hordeum vulgare) were oxidized, using different concentrations of hydrogen
      peroxide (0.2-1.0% H2O2). The total and soluble beta-glucan contents ranged from
      8.41% and 4.81% in the control to 9.48% and 6.45% in the 0.6% H2O2 treatment.
      With increasing H2O2 concentration, the purity of beta-glucan increased from 35%
      to 70%, whereas molecular weight (MW), viscosity, and water-binding capacities
      decreased to 2.0 * 10(4)Da, 3.9 cP, and 4.45 g water/g beta-glucan, respectively.
      Oil binding capacities ranged from 8.29 g of oil/g in non-oxidized beta-glucan to
      9.42 g of oil/g in beta-glucan oxidized with 0.6% H2O2. The MW, viscosity, and
      binding capacities of waxy barley beta-glucan were higher than those of non-waxy
      barley beta-glucan. Oxidation by hydrogen peroxide improved the physical
      properties and in vitro binding capacity of barley beta-glucan.

PMID- 26304405
TI  - Correlation between volatile profiles of Italian fermented sausages and their
      size and starter culture.
AB  - The aroma profiles of 10 traditional Italian fermented sausages were evaluated.
      The volatile organic compounds (VOCs) obtained by solid-phase microextraction and
      gas chromatograph-mass spectrometry were analysed using principal component
      analysis (PCA) and linear discriminant analysis (LDA). PCA allowed an acceptable
      separation but some sausage typologies were not well separated. On the other
      hand, the supervised approach of LDA allowed a clear grouping of the samples in
      relation to sausage size and starter culture. In spite of the extreme variability
      of the volatile profiles of the sausage typologies, this work showed the
      influence of diameter on VOC profile. The differences observed can be related to
      the effects that some fundamental physicochemical characteristics (such as water
      loss kinetics and oxygen availability) have on the results of ripening processes.
      Differences in VOC profiles were also observed due to the lactic acid bacteria
      used as starter cultures, with differences mainly attributable to compounds
      deriving from pyruvate metabolism. 

PMID- 26304406
TI  - The development of a hexaplex-conventional PCR for identification of six animal
      and plant species in foodstuffs.
AB  - A hexaplex-conventional PCR assay was developed for identification of five meat
      and one plant species origins in foodstuffs simultaneously. The method merges the
      use of horse (Equus caballus), soybean (Glycine max), sheep (Ovis aries), poultry
      (Meleagris meleagris), pork (Sus scrofa), and cow (Bos taurus) specific primers
      that amplify fragments (horse; 85 bp, soybean; 100 bp, sheep; 119 bp, poultry;
      183 bp, pork; 212 bp and cow; 271 bp) of the mitochondrial cyt b, lectin, 12S
      rRNA, 12S rRNA, ATPase subunit 6 genes and ATPase subunit 8 genes respectively,
      and a universal 18S rRNA primers that amplifies a 141 bp. Multiplex analysis of
      the reference food samples showed that detection limit of the hexaplex assay was
      0.01% for each species. Taken together, all data indicated that this hexaplex PCR
      assay was a simple, fast, sensitive, specific, and cost-effective detection
      method for horse, soybean, sheep, poultry, pork and cow species in foodstuffs.

PMID- 26304407
TI  - Nutritional quality and ions uptake to PTNDS in soybeans.
AB  - Porous-tube nutrient delivery system (PTNDS) allows high control of the root
      environment and prevents plant infections in both microgravity and ground
      conditions. In this paper, six soybean cultivars ('ZH13', 'ZH57', 'LD10', 'HH35',
      'HH43', and 'ZGDD') were evaluated in terms of yield, photosynthetic efficiency,
      insoluble dietary fiber and ions uptake efficiency. Besides proximal composition,
      the concentrations of mineral and isoflavones were monitored in the seeds. 'HH35'
      and 'ZH13' plants showed much higher yield and harvest index, in addition to the
      lower lignin content of inedible biomass. Data showed that 'HH35' had the higher
      photosynthetic efficiency of soybean leaves with regard to photosynthetic rate
      and instantaneous carboxylation efficiency, whereas chlorophyll ratio and
      carotenoids content were no difference with the other cultivars. Both cations and
      anions except NH4(+) and H2PO4(-), were accumulated excessively compared to
      controls, especially with anions in PTNDS. 

PMID- 26304408
TI  - Quantitative determination of casein genetic variants in goat milk: Application
      in Girgentana dairy goat breed.
AB  - The study was conducted to develop a high-performance liquid chromatographic
      (HPLC) method to quantify casein genetic variants (alphas2-, beta-, and kappa
      casein) in milk of homozygous individuals of Girgentana goat breed. For
      calibration experiments, pure genetic variants were extracted from individual
      milk samples of animals with known genotypes. The described HPLC approach was
      precise, accurate and highly suitable for quantification of goat casein genetic
      variants of homozygous individuals. The amount of each casein per allele was:
      alphas2-casein A = 2.9 +/- 0.8 g/L and F = 1.8 +/- 0.4 g/L; beta-casein C = 3.0
      +/- 0.8 g/L and C1 = 2.0 +/- 0.7 g/L and kappa-casein A = 1.6 +/- 0.3 g/L and B =
      1.1 +/- 0.2 g/L. A good correlation was found between the quantities of alphas2
      casein genetic variants A and F, and beta-casein C and C1 with other previously
      described method. The main important result was obtained for kappa-casein
      because, till now, no data were available on quantification of single genetic
      variants for this protein.

PMID- 26304409
TI  - Volumetric and UV absorption studies on understanding the solvation behavior of
      polyhydroxy solutes in l-ascorbic acid(aq) solutions at T=(288.15 to 318.15)K.
AB  - Thermodynamic and spectroscopic data characterizing the solvation behavior of
      polyhydroxy compounds are in demand to get better understanding about the
      mechanisms of taste chemoreception, protein stabilization, etc. Apparent molar
      volumes for monosaccharides, disaccharides, derivatives, and polyols in (0.05,
      0.15, 0.25 and 0.35) mol kg(-1) aqueous solutions of l-ascorbic acid have been
      determined from density data measured at (288.15, 298.15, 308.15 and 318.15)K
      under atmospheric pressure. Standard partial molar volumes at infinite-dilution
      and corresponding volumes of transfer of solutes from water to L-ascorbic
      acid(aq) have been calculated. Interaction coefficients and standard partial
      molar expansibilities have also been evaluated. The basic taste quality of
      studied solutes has been assessed from apparent massic volumes. UV absorption
      studies support the interactions between solutes and L-ascorbic acid. Influence
      of pH variation was taken into consideration while evaluating chemical behavior
      and stability of L-ascorbic acid in aqueous and buffer solutions.

PMID- 26304410
TI  - NaOH-free debittering of table olives using power ultrasound.
AB  - A major drawback to the extension of NaOH-free olive debittering is its lengthy
      processing. In this research, the power ultrasound efficacy was investigated in a
      laboratory scale to accelerate this process. Olive fruits were sonicated in water
      or brine (15% NaCl). The effects of ultrasound-assisted debittering (UAD) were
      evaluated on olives physicochemical and textural properties in comparison with
      conventional debittering (CD). In UAD, however, the removal rate of phenolic
      compounds, which cause olives natural bitterness, increased significantly and as
      a result, the processing time decreased by 37.8% and 38.6% when debittering was
      done in water and brine, respectively. The chemical compositions, fatty acids
      profile, total color differences, Firmness and other textural parameters of UAD
      treated samples remained unchanged and their antioxidant activity was
      significantly higher in comparison with CD-treated samples. Remarkably, UAD was
      able to speed up and promote NaOH-free olive debittering, without causing any
      undesirable changes. 

PMID- 26304412
TI  - Statistical framework for detection of genetically modified organisms based on
      Next Generation Sequencing.
AB  - Because the number and diversity of genetically modified (GM) crops has
      significantly increased, their analysis based on real-time PCR (qPCR) methods is
      becoming increasingly complex and laborious. While several pioneers already
      investigated Next Generation Sequencing (NGS) as an alternative to qPCR, its
      practical use has not been assessed for routine analysis. In this study a
      statistical framework was developed to predict the number of NGS reads needed to
      detect transgene sequences, to prove their integration into the host genome and
      to identify the specific transgene event in a sample with known composition. This
      framework was validated by applying it to experimental data from food matrices
      composed of pure GM rice, processed GM rice (noodles) or a 10% GM/non-GM rice
      mixture, revealing some influential factors. Finally, feasibility of NGS for
      routine analysis of GM crops was investigated by applying the framework to
      samples commonly encountered in routine analysis of GM crops. 

PMID- 26304411
TI  - Isofuranodiene: A neuritogenic compound isolated from wild celery (Smyrnium
      olusatrum L., Apiaceae).
AB  - In the search for neuroactive compounds that mimic the nerve growth factor (NGF)
      activity for the protection against neurodegenerative diseases, the potential
      medicinal values of foods and plants attracts intense interest. Isofuranodiene is
      the major constituent of the essential oil of wild celery (Smyrnium olusatrum L.,
      Apiaceae). The cytotoxic effects of isofuranodiene towards rat neuronal PC-12
      pheochromocytoma cells were determined by MTT assay, while the cell
      differentiation was evaluated with xCELLigence real time cell analysis system
      (RTCA DP), and the neuritogenic activity was assessed by neurite outgrowth image
      analysis. Isofuranodiene at concentrations of 25 and 12.5 MUM alone, or in
      combination with 50 nM NGF, showed a marked stimulation of neuritogenesis, but it
      was more effective at 12.5 MUM with or without NGF. The present study reports the
      first evidence of the neuritogenic effects of isofuranodiene, which appears to be
      a promising neurotrophic and neuroprotective agent deserving further
      investigation.

PMID- 26304413
TI  - Sensitive quantitation of Ochratoxin A in cocoa beans using differential pulse
      voltammetry based aptasensor.
AB  - In this work, we propose for the first time a sensitive Ochratoxin A (OTA)
      detection in cocoa beans using competitive aptasensor by differential pulse
      voltammetry (DPV). In the proposed method, biotin labeled and free OTA competed
      to bind with immobilized aptamer onto the surface of a screen printed carbon
      electrode (SPCE), and percentage binding was calculated. The detection was
      performed after adding avidin-ALP to perform avidin-biotin reaction; the signal
      was generated through a suitable substrate 1-naphthyl phosphate (1-NP), for
      alkaline phosphatase (ALP). The cocoa samples were extracted and purified using
      molecular imprinted polymer (MIP) columns specifically designed for OTA. The
      developed aptasensor showed a good linearity in the range 0.15-5 ng/mL with the
      limit of detection (LOD) 0.07 ng/mL and 3.7% relative standard deviation (RSD).
      The aptasensor displayed good recovery values in the range 82.1-85% with 3.87%
      RSD, thus, demonstrated the efficiency of proposed aptasensor for such matrices.

PMID- 26304414
TI  - Impact of selected composition and ripening conditions on CO2 solubility in semi
      hard cheese.
AB  - Despite CO2 being one of the most important gases affecting the quality of most
      semi-hard cheeses, the thermodynamic properties of this molecule in relation to
      cheese ripening have rarely been investigated. In this study the CO2 solubility
      coefficient was experimentally assessed in semi-hard cheese as a function of the
      most relevant compositional and ripening variables. As expected, CO2 solubility
      was found to linearly decrease with temperature in the range 2-25  degrees C.
      Unexpectedly, solubility was not significantly different at 39% and 48% moisture,
      while it was found lower at 42%. Unavoidable changes in protein content of the
      three cheese variants is suspected to produce an interaction with water content,
      leading to complex interpretation of the results. Increasing salt content in
      cheese from 0 to 2.7%w/w significantly decreased CO2 solubility by about 25%,
      probably due to the increased bonded water molecules in the cheese water phase.

PMID- 26304415
TI  - Methods for the analysis of azo dyes employed in food industry--A review.
AB  - A wide variety of azo dyes are generally added for coloring food products not
      only to make them visually aesthetic but also to reinstate the original
      appearance lost during the production process. However, many countries in the
      world have banned the use of most of the azo dyes in food and their usage is
      highly regulated by domestic and export food supplies. The regulatory authorities
      and food analysts adopt highly sensitive and selective analytical methods for
      monitoring as well as assuring the quality and safety of food products. The
      present manuscript presents a comprehensive review of various analytical
      techniques used in the analysis of azo dyes employed in food industries of
      different parts of the world. A brief description on the use of different
      extraction methods such as liquid-liquid, solid phase and membrane extraction has
      also been presented. 

PMID- 26304416
TI  - Determination of tocopherols and sitosterols in seeds and nuts by QuEChERS-liquid
      chromatography.
AB  - In the present work a simple, reliable and affordable sample treatment method for
      the simultaneous analysis of tocopherols and free phytosterols in nuts was
      developed. Analyte extraction was carried out using the QuEChERS methodology and
      analyte separation and detection were accomplished using HPLC-DAD. The use of
      this methodology for the extraction of natural occurring substances provides
      advantages such as speed, simplicity and ease of use. The parameters evaluated
      for the validation of the method developed included the linearity of the
      calibration plots, the detection and quantification limits, repeatability,
      reproducibility and recovery. The proposed method was successfully applied to the
      analysis of tocopherols and free phytosterols in samples of almonds, cashew nuts,
      hazelnuts, peanuts, tiger nuts, sun flower seeds and pistachios. 

PMID- 26304417
TI  - Maillard conjugation of lactulose with potentially bioactive peptides.
AB  - Milk ultrafiltration permeate was heated at 97  degrees C in the presence of
      eggshell for 60 min. This decreased the ash content of permeate and converted ~
      17% of lactose to lactulose. The isomerized permeate was subsequently purified to
      a lactulose-rich product (LRP; ~ 70% lactulose content to total sugar) through
      crystallizing lactose out by methanol. The LRP and lactose were then conjugated
      with either whey protein isolate (WPI) or its antioxidant hydrolysate (WPH)
      through Maillard reaction at 90  degrees C. The amount of the Maillard reaction
      advanced products was higher for WPI-lactose system than WPH-lactose counterpart;
      whilst, the DPPH scavenging activities of WPH-sugar conjugates were significantly
      higher than those of WPI-sugar counterparts. Based on free amino groups content
      measurement, it was found that lactose is more reactive than LRP for Maillard
      conjugation with both WPI and WPH. Fourier transform infrared spectroscopy
      confirmed the bonding of the anomeric region of saccharide configuration of
      lactulose with WPH.

PMID- 26304418
TI  - Preliminary results of mercury levels in raw and cooked seafood and their public
      health impact.
AB  - Mercury is toxic for human health and one of the main routes of exposure is
      through consumption of contaminated fish and shellfish. The objective of this
      work was to assess the possible mercury contamination of bivalves (Anomalocardia
      brasiliana, Lucina pectinata, Callinectes sapidus), crustacean (C. sapidus) and
      fish (Bagre marinus and Diapterus rhombeus) collected on Salinas da Margarida, BA
      (Brazil), a region which carciniculture, fishing and shellfish extraction are the
      most important economic activities. The effect of cooking on Hg concentration in
      the samples was also studied. The results showed that Hg concentration was
      generally higher in the cooked samples than in raw samples. This increase can be
      related to the effect of Hg pre-concentration, formation of complexes involving
      mercury species and sulfhydryl groups present in tissues and/or loss of water and
      fat. The highest concentrations were found in B. marinus samples ranging 837.0
      1585.3 MUg kg(-1), which exceeded those recommended by Brazilian Health
      Surveillance Agency (ANVISA). In addition, Hg values found in the other samples
      also suggest the monitoring of the Hg concentrations in seafood consumed from the
      region.

PMID- 26304419
TI  - Extraction assisted by pulsed electric energy as a potential tool for green and
      sustainable recovery of nutritionally valuable compounds from mango peels.
AB  - The study compares the efficiency of conventional aqueous extraction at different
      temperatures (20-60  degrees C) and pH (2.5-11) and extraction assisted by pulsed
      electric energy (pulsed electric fields, PEF or high voltage electrical
      discharges, HVED) of nutritionally valuable compounds found in mango peels.
      Exponential decay pulses with initial electric field strengths of ~ 13.3 kV/cm
      and ~ 40 kV/cm for PEF and HVED treatments were used, respectively. The impact of
      temperature on aqueous extraction of proteins and carbohydrates was not
      significant. The highest values of nutritionally valuable and antioxidant
      compounds (7.5mM TE) were obtained for aqueous extraction (T = 60  degrees C, pH
      6) but extracts were unstable and cloudy. The application of two-stage procedure
      PEF+supplementary aqueous extraction (+SE) that include PEF-assisted extraction
      as the first step, and +SE at 50  degrees C, pH 6 during 3h as the second step,
      allowed a noticeable enhancement of the yields of TPC (+400%) even at normal pH.

PMID- 26304420
TI  - Effect of drying methods on the quality characteristics of dill (Anethum
      graveolens) greens.
AB  - Different drying methods hot air (HA), 50  degrees C, 58-63% relative humidity
      (RH); low humidity air (LHA), 50  degrees C and 28-30% RH; and radiofrequency
      (RF), 50  degrees C, 56-60% RH) were investigated for efficient dehydration of
      dill (Anethum graveolens) greens with optimal retention of color and
      constituents. The drying for HA and RF was marginally higher (~ 22%) compared to
      HA. Lightness, greenness and yellowness of LHA dried sample were higher than
      those of the RF and hot-air dried dill greens. Aqueous methanolic extract of dill
      greens dehydrated by LHA method exhibited higher anti-oxidant activity. Forty-two
      compounds were identified representing ~ 85% of the volatile oil and the major
      volatile compounds for fresh and dried dill leaf oil were alpha-Phellandrene,
      alpha-cymene, alpha-pinene, Apiol, 1,6-Cyclodecodiene, and 1-methyl-5-methylene.
      Dehydrated dill greens with their constituent polyphenols, carotenoids, ascorbic
      acid and minerals have been shown good consumer acceptance as well as shelf life
      and could serve as a valuable food additive to enhance human nutrition.

PMID- 26304421
TI  - Impact of epsilon-polylysine and pectin on the potential gastrointestinal fate of
      emulsified lipids: In vitro mouth, stomach and small intestine model.
AB  - epsilon-Polylysine (epsilon-PL) is a broad-spectrum antimicrobial biopolymer,
      suitable for use in foods; however, some studies suggest that it may also inhibit
      lipid digestion. We therefore examined the effect of polylysine on the digestion
      of corn oil-in-water emulsions, using a simulated gastrointestinal tract (GIT)
      that included oral, gastric, and intestinal phases. Both mucin and polylysine had
      pronounced influences on the particle size, charge, and aggregation state
      throughout the GIT. However, surprisingly, we found that epsilon-polylysine did
      not have a significant impact on lipid digestion, either in the presence or
      absence of anionic mucin. However, it did form strong electrostatic complexes
      with mixed micelles, which could decrease the transport and absorption of lipids
      in the small intestine. These results have important implications for the
      incorporation of polylysine into food systems, particularly those containing
      lipophilic nutrients. 

PMID- 26304422
TI  - Characterization of starch films impregnated with starch nanoparticles prepared
      by 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-mediated oxidation.
AB  - In this work, we investigated the effects of adding different contents (0%, 0.5%,
      1%, 2%, 5%, wt% based on maize starch, dsb) of starch nanoparticles prepared by
      the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-mediated oxidation (TEMPO-SNPs)
      on the properties of maize starch films. Differential scanning calorimetry, X-ray
      diffraction analysis, scanning electron microscopy (SEM), transmission electron
      microscopy and texture profile analysis were used to characterize the thermal
      properties, morphology and structure of the prepared films. As the content of
      TEMPO-SNPs increased, the water vapor permeability (WVP) of films reduced
      significantly from 4.21 * 10(-8) to 3.04 * 10(-8) gm(-1) s(-1) Pa(-1).
      Furthermore, elongation at break, tensile strength and Young's modulus of the
      films increased as the TEMPO-SNPs content increased. At the TEMPO-SNPs content of
      1%, the elongation at break, the tensile strength and Young's modulus of the
      films peaked. SEM showed that the nanocomposite films had smoother surfaces and
      cross sections with no cracks or visible air pockets.

PMID- 26304423
TI  - Variation in mineral elements in grains of 20 brown rice accessions in two
      environments.
AB  - Twenty rice accessions were planted in Hainan province, China, for 2 years to
      investigate the effects of genotype, environment, and their interactions on the
      Ca, Mg, Na, K, Fe, Zn, and Cu contents in brown rice. Analysis of variance showed
      that the Ca, Na and K were mainly affected by the genotypic variance, whereas the
      Fe, Zn and Cu were mainly affected by the environment variance. The genotype *
      environment interaction effects for Mg, Na, Zn, and Cu were highly significant (P
      < 0.001), though it only accounted for a small proportion of the total variation
      (0.5-16.3%). The correlation analyses showed that Mg was significantly positively
      correlated with K, Fe, and Zn. A total of 9 and 8 single nucleotide polymorphism
      (SNP) loci were identified in 2011 and 2012, respectively, which were strongly
      associated with for Ca, Cu, K, Na, and Zn.

PMID- 26304424
TI  - The role of various amino acids in enzymatic browning process in potato tubers,
      and identifying the browning products.
AB  - The effects of five structurally variant amino acids, glycine, valine,
      methionine, phenylalanine and cysteine were examined as inhibitors and/or
      stimulators of fresh-cut potato browning. The first four amino acids showed
      conflict effects; high concentrations (? 100mM for glycine and ? 1.0M for the
      other three amino acids) induced potato browning while lower concentrations
      reduced the browning process. Alternatively, increasing cysteine concentration
      consistently reduced the browning process due to reaction with quinone to give
      colorless adduct. In PPO assay, high concentrations (? 1.11 mM) of the four amino
      acids developed more color than that of control samples. Visible spectra
      indicated a continuous condensation of quinone and glycine to give colored
      adducts absorbed at 610-630 nm which were separated and identified by LC-ESI-MS
      as catechol-diglycine adduct that undergoes polymerization with other glycine
      molecules to form peptide side chains. In lower concentrations, the less
      concentration the less developed color was observed.

PMID- 26304425
TI  - Evolution of metabolomics profile of crab paste during fermentation.
AB  - Crab paste is regularly consumed by people in the coastal area of China. The
      fermentation time plays a key role on the quality of crab paste. Here, we
      investigated the dynamic evolution of metabolite profile of crab paste during
      fermentation by combined use of NMR spectroscopy and multivariate data analysis.
      Our results showed that crab paste quality was significantly affected by
      fermentation. The quality change was manifested in the decline of lactate,
      betaine, taurine, trimethylamine-N-oxide, trigonelline, inosine, adenosine
      diphosphate, and 2-pyridinemethanol, and in the fluctuation of a range of amino
      acids as well as in the accumulation of glutamate, sucrose, formate, acetate,
      trimethylamine, and hypoxanthine. Trimethylamine production and its increased
      level with fermentation could be considered as a freshness index of crab paste.
      These results contribute to quality assessment of crab paste and confirm the
      metabolomics technique as a useful tool to provide important information on the
      crab paste quality. 

PMID- 26304426
TI  - Chemometric-assisted QuEChERS extraction method for the residual analysis of
      thiacloprid, spirotetramat and spirotetramat's four metabolites in pepper:
      Application of their dissipation patterns.
AB  - Chemometric tools equipped with a Plackett-Burman (P-B) design, a central
      composite design (CCD) and a desirability profile were employed to optimise the
      QuEChERS (quick, easy, cheap, effective, rugged and safe) method for the
      quantification of thiacloprid, spirotetramat and spirotetramat's four metabolites
      in pepper. The average recoveries were in the range of 71.6-119.5%, with relative
      standard deviations ? 12.1%. The limit of quantification for the method was less
      than 0.01 mg/kg. The method was applied to field samples to evaluate the residual
      characteristics of thiacloprid and spirotetramat. The data showed that the
      first+first-order model is a better fit than the first order model for the
      dissipation of thiacloprid and spirotetramat in pepper. The half-lives of
      thiacloprid and spirotetramat in pepper are 0.81 and 1.21 days, respectively. The
      final residues were between 0.016 mg/kg and 0.13 mg/kg for thiacloprid and 0.08
      mg/kg and 0.12 mg/kg for spirotetramat.

PMID- 26304427
TI  - Analysis of 19 PCB congeners in catfish tissue using a modified QuEChERS method
      with GC-MS/MS.
AB  - A simple approach to determine 19 PCB congeners in catfish tissue was presented.
      A modified QuEChERS method employing high solvent to sample ratio 10:1 was used
      to improve the extraction recovery of 19 PCB congeners. After salting out by
      shaking with anhydrous magnesium sulfate and sodium chloride, 1 mL of
      acetonitrile extract was pipetted into a 2-mL centrifuge tube containing
      anhydrous magnesium sulfate, primary secondary amine sorbent, and C-18 sorbent.
      The tube was then shaken and centrifuged to absorb fat and fatty acid residue
      present in the acetonitrile extract. The acetonitrile extract was analyzed by GC
      MS/MS. The excellent sensitivity of GC-MS/MS allows for the direct injection of
      the samples to detect the low level of the PCB congeners. The method therefore is
      high throughput, uses fewer consumable lab supplies, and provides excellent
      sensitivity with an LOQ below 1 ng/g.

PMID- 26304428
TI  - Comparative study of biological activities and phytochemical composition of two
      rose hips and their preserves: Rosa canina L. and Rosa arvensis Huds.
AB  - The aim of this study was to compare phenolic profile, vitamin C content,
      antioxidant, anti-inflammatory and cytotoxic activity of rose hips and the
      preserves (puree and jam) of two Rosa species: renowned Rosa canina L. and
      unexplored Rosa arvensis Huds. The liquid chromatography-tandem mass spectrometry
      analysis of 45 phenolics resulted in quantification of 14 compounds, with
      quercitrin, gallic and protocatechuic acids as the most dominant. High
      antioxidant potential of R. canina and a moderate activity of R. arvensis
      extracts were determined through several assays. Puree of both species and
      methanol extract of air-dried R. canina hips showed some anti-inflammatory
      (cyclooxygenase-1 and 12-lipooxygense inhibition potency) activity. Puree of R.
      canina exerted cytotoxic activity only against the HeLa cell line among several
      others (HeLa, MCF7, HT-29 and MRC-5). The presented results support traditional
      use of rose hips and their fruit preserves as food with health and nutritional
      benefits. 

PMID- 26304429
TI  - Bioavailability and biodistribution of nanodelivered lutein.
AB  - The aim of the study was to evaluate the ability of poly(lactic-co-glycolic acid)
      (PLGA) nanoparticles (NP) to enhance lutein bioavailability. The bioavailability
      of free lutein and PLGA-NP lutein in rats was assessed by determining plasma
      pharmacokinetics and deposition in selected tissues. Lutein uptake and secretion
      was also assessed in Caco-2 cells. Compared to free lutein, PLGA-NP increased the
      maximal plasma concentration (Cmax) and area under the time-concentration curve
      in rats by 54.5- and 77.6-fold, respectively, while promoting tissue accumulation
      in the mesenteric fat and spleen. In comparison with micellized lutein, PLGA-NP
      lutein improved the Cmax in rat plasma by 15.6-fold and in selected tissues by ?
      3.8-fold. In contrast, PLGA-NP lutein had a lower uptake and secretion of lutein
      in Caco-2 cells by 10.0- and 50.5-fold, respectively, compared to micellized
      lutein. In conclusion, delivery of lutein with polymeric NP may be an approach to
      improve the bioavailability of lutein in vivo.

PMID- 26304430
TI  - Application of the rat liver lysosome assay to determining the reduction of toxic
      gliadin content during breadmaking.
AB  - Enriched caricain was able to detoxify a major proportion of the gliadin in
      wholemeal wheat dough by allowing it to react for 5h at 37  degrees C during the
      fermentation stage. A reduction of 82% in toxicity, as determined by the rat
      liver lysosome assay, was achieved using 0.03% enzyme on weight of dough. Without
      enzyme, only 26% reduction occurred. The difference in reduction of toxicity
      achieved is statistically significant (p < 0.01). The results are very similar to
      those obtained in our previous work using an immuno assay and the same enzyme
      preparation. They confirm the value of caricain as a means of reducing the
      toxicity of gliadin and open the way for enzyme therapy as an adjunct to the
      gluten free diet. This approach should lead to better control over the
      elimination of dietary gluten intake in conditions such as coeliac disease and
      dermatitis herpetiformis.

PMID- 26304431
TI  - The effects of GA and ABA treatments on metabolite profile of germinating barley.
AB  - Sugar degradation during grain germination is important for malt quality. In
      malting industry, gibberellin (GA) is frequently used for improvement of malting
      quality. In this study, the changes of metabolite profiles and starch-degrading
      enzymes during grain germination, and as affected by GA and abscisic acid (ABA)
      were investigated using two wild barley accessions XZ72 and XZ95. Totally fifty
      two metabolites with known structures were detected and the change of metabolite
      during germination was time- and genotype dependent. Sugars and amino acids were
      the most dramatically changed compounds. Addition of GA enhanced the activities
      of starch-degrading enzymes, and increased most metabolites, especially sugars
      and amino acids, whereas ABA had the opposite effect. The effect varied with the
      barley accessions. The current study is the first attempt in investigating the
      effect of hormones on metabolite profiles in germinating barley grain, being
      helpful for identifying the factors affecting barley germination or malt quality.

PMID- 26304432
TI  - Development of a barcode-style lateral flow immunoassay for the rapid semi
      quantification of gliadin in foods.
AB  - In this work, a barcode-style lateral flow immunoassay is developed using two cut
      off values (10 and 50 mg kg(-1) gliadin) to provide a semi-quantification for
      identifying "gluten-free" and "very low gluten" foods, based on the international
      Codex Alimentarius Standard. This developed assay exhibits favorable specificity
      in differentiating wheat from seven commonly used grains, with only a slight
      cross-reaction with barely. The intra-assay and inter-assay CV values of this
      assay were 1.5-1.7% and 2.5-4.5%, respectively, revealing high reproducibility.
      In the analysis of 48 food samples, the results of this assay closely agreed with
      those obtained using AOAC-approved ELISA or strip kits, as the Cohen's kappa
      coefficients for both comparisons exceeded 0.8. Thus, this developed assay can be
      used to quickly estimate the gliadin content in foods in order to protect people
      with wheat allergy or celiac disease from the accidental ingestion of gliadin.

PMID- 26304433
TI  - Reduced beta-lactoglobulin IgE binding upon in vitro digestion as a result of the
      interaction of the protein with casein glycomacropeptide.
AB  - The aim of this work was to evaluate the effect of the presence of casein
      glycomacropeptide (CMP) on the in vitro digestibility and potential allergenicity
      of beta-lactoglobulin (beta-lg)-CMP mixtures. The digestion products were
      analyzed by RP-HPLC and RP-HPLC-ESI-MS/MS. The potential allergenicity of the
      digestion products was studied by human IgE binding by inhibition ELISA with
      serum samples from children with clinical allergic symptoms to beta-lg. No
      differences were observed by HPLC in the mixtures hydrolysates due to CMP-beta-lg
      interactions. RP-HPLC-ESI-MS/MS results showed different peptides occurring in
      the mixtures hydrolysates. Additionally, it was observed a significant reduction
      of beta-lg IgE binding in the presence of CMP. The disappearance of epitopes in
      the digested mixtures could explain the lower IgE binding observed in these
      systems compared to beta-lg. It can be concluded that the presence of CMP in
      products containing beta-lg may modify the digestion products that may reduce the
      potential allergenicity of beta-lg. 

PMID- 26304434
TI  - Influence of the incorporation of fibers in biscuit dough on proton mobility
      characterized by time domain NMR.
AB  - The effect of fiber addition on the distribution and mobility of protons in
      biscuits is studied by using low resolution time domain nuclear magnetic
      resonance (TD-NMR). The proportion of flour is reduced in order to incorporate
      inulin and oat fiber. NMR temperature dependent experiments are carried out in
      order to gain insight on the processes occurring in biscuit baking. Proton
      populations were identified measuring spin-spin relaxation times (T2). The major
      change in the relaxation profiles upon incorporation of fibers corresponds to
      mobile water molecules, which appear to be related to dough spreading behavior
      and biscuit quality. Biscuit samples baked in a commercial oven were studied by
      two dimensional spin-lattice/spin-spin (T1-T2) relaxation maps. The T1/T2 ratio
      is used as an indicator of the population mobility, where changes in the mobility
      of water in contact with flour components as starch, proteins and pentosans are
      observed. 

PMID- 26304435
TI  - Impact of fermentation on nitrogenous compounds of cocoa beans (Theobroma cacao
      L.) from various origins.
AB  - Tangential filtration technique was used to separate and quantify three different
      fractions of nitrogenous compounds depending on their molecular size, during
      cocoa fermentation. On every phenotype and origin analyzed, protein profile of
      non-fermented samples was similar. During fermentation course, proteins get
      degraded with a concomitant increase in amino acids content. Peptides between 3
      and 10 kDa were observed at low levels. A strong correlation between amino acids
      and ammonia nitrogen, a fermentation marker was found. Attention was drawn on
      each fraction, and enabled to point out other phenomenon occurring during
      fermentation. The migration of some nitrogenous compounds towards the bean shell
      during fermentation was demonstrated. Acetone treatment of cocoa powder prior to
      SDS-PAGE led to losses of nitrogenous compounds. This result gives clues on the
      tanning phenomenon carried out by polyphenols on nitrogenous compounds,
      phenomenon which increases during fermentation.

PMID- 26304436
TI  - Lipid nutritional value of legumes: Evaluation of different extraction methods
      and determination of fatty acid composition.
AB  - This study sought to contribute to the assessment of the nutritional properties
      of legumes by determining the fatty acid (FA) composition of 29 legume samples
      after the evaluation of nine extraction methods. The Folch method and liquid
      solid extraction with hexane/isopropanol or with hexane/acetone were
      investigated, as was the effect of previous hydration of samples. Soxhlet
      extractions were also evaluated with different solvent mixtures. Results on FA
      composition using the hexane/isopropanol extraction method were the same in terms
      of FA composition of the Folch method, but the extraction yield was only around
      20-40% of that of the Folch method preceded by hydration. Some types of legumes
      showed particularly interesting values for the ratio of polyunsaturated fatty
      acids (PUFAs) n-6/n-3, such as lentils, with the value of 4.0, and Azuki beans,
      at 3.2. In lentils, the PUFAs% ranged from 42.0% to 57.4%, while in Azuki beans
      it was 57.5%. 

PMID- 26304437
TI  - Sucrose behenate as a crystallization enhancer for soft fats.
AB  - The addition of sucrose behenate for the modification of the physical properties
      of soft fats, such as soybean oil-based interesterified fat, refined palm oil,
      and palm mid fraction was studied. The addition of sucrose behenate was verified
      to affect the crystalline network of fats, changing the hardness and solids
      profile. The isothermal crystallization behaviors of the fat blends with 1%
      sucrose behenate were analyzed at 20 and 25  degrees C. Temperature had a greater
      effect on the speed of crystallization (k) than the presence of the emulsifier.
      Sucrose behenate did, however, influence the crystallization mechanism, with
      changes observed in the Avrami exponent (n). These changes were also observed in
      the microstructure of the fats. Changes in the polymorphic behavior were observed
      with the addition of sucrose behenate, such as a possible delay in the alpha ->
      beta transition for interesterified fat, and the initial formation of the beta
      polymorph in palm oil.

PMID- 26304438
TI  - Characterisation and identification of triterpene saponins in the roots of red
      beets (Beta vulgaris L.) using two HPLC-MS systems.
AB  - Triterpene saponins are important bioactive constituents with an enormous variety
      in structure widely distributed in many plants. Here, we profiled triterpene
      saponins from the skin and flesh of red beetroot Beta vulgaris L. cultivars
      Nochowski from 2012 and 2013 season using reversed-phase liquid chromatography
      combined with negative-ion electrospray ionisation quadrupole mass spectrometry.
      We tentatively identified 44 triterpene saponins, of which 37 had not been
      detected previously in the root of red beets and 27 saponins were tentatively
      identified as potentially new compounds. All observed compounds were glycosides
      of four different aglycone structures, of which akebonoic acid and gypsogenin
      were not detected previous in red beetroot. Based on the high-resolution mass
      measurements among these 44 detected saponins 10 groups of isomers were
      identified. We report for the first time that 18 saponins with dioxolane-type (2
      saponins) and acetal-type (16 saponins) substituents were detected in the roots
      of red beet. 

PMID- 26304439
TI  - Application of cross-linked and hydrolyzed arabinoxylans in baking of model rye
      bread.
AB  - The role of water extractable arabinoxylan with varying molar mass and structure
      (cross-linked vs. hydrolyzed) in the structure formation of rye bread was
      examined using a model bread. Instead of the normal flour, the dough contained
      starch, arabinoxylan and protein, which were isolated from rye wholemeal. It was
      observed that the applied mixes of these constituents result in a product closely
      resembling typical rye bread, even if arabinoxylan was modified (by cross-linking
      or hydrolysis). The levels of arabinoxylan required for bread preparation
      depended on its modification and mix composition. At 3% protein, the maximum
      applicable level of poorly soluble cross-linked arabinoxylan was 3%, as higher
      amounts of this preparation resulted in an extensively viscous dough and
      diminished bread volume. On the other hand highly soluble, hydrolyzed
      arabinoxylan could be used at a higher level (6%) together with larger amounts of
      rye protein (3% or 6%). Further addition of arabinoxylan leads to excessive water
      absorption, resulting in a decreased viscosity of the dough during baking and
      insufficient gas retention. 

PMID- 26304440
TI  - Stable isotope ratio analysis: A potential analytical tool for the authentication
      of South African lamb meat.
AB  - Stable isotope ratios ((13)C/(12)C and (15)N/(14)N) of South African Dorper lambs
      from farms with different vegetation types were measured by isotope ratio mass
      spectrometry (IRMS), to evaluate it as a tool for the authentication of origin
      and feeding regime. Homogenised and defatted meat of the Longissimus lumborum
      (LL) muscle of lambs from seven different farms was assessed. The delta(13)C
      values were affected by the origin of the meat, mainly reflecting the diet. The
      Ruens and Free State farms had the lowest (p ? 0.05) delta(15)N values, followed
      by the Northern Cape farms, with Hantam Karoo/Calvinia having the highest
      delta(15)N values. Discriminant analysis showed delta(13)C and delta(15)N
      differences as promising results for the use of IRMS as a reliable analytical
      tool for lamb meat authentication. The results suggest that diet, linked to
      origin, is an important factor to consider regarding region of origin
      classification for South African lamb.

PMID- 26304441
TI  - Fluorescence markers in some New Zealand honeys.
AB  - The fluorescence characteristics of various New Zealand honeys were investigated
      to establish if this technique might detect signatures unique to manuka
      (Leptospermum scoparium) and kanuka (Kunzea ericoides) honeys. We found unique
      fluorescence profiles for these honeys which distinguished them from other New
      Zealand honey floral types. Two excitation-emission (ex-em) marker wavelengths
      each for manuka and kanuka honeys were identified; manuka honey at 270-365 (MM1)
      and 330-470 (MM2) nm and kanuka honey at 275-305 (KM1) and 445-525 (KM2) nm.
      Dilution of manuka and kanuka honeys with other honey types that did not possess
      these fluorescence profiles resulted in a proportional reduction in fluorescence
      signal of the honeys at the marker wavelengths. By comparison, rewarewa (Knightia
      excelsa), kamahi (Weinmannia racemosa), and clover (Trifolium spp.) honeys did
      not exhibit unique fluorescence patterns. These findings suggests that a
      fluorescence-based screening approach has potential utility for determining the
      monoflorality status of manuka and kanuka honeys. 

PMID- 26304442
TI  - Classification of red wines using suitable markers coupled with multivariate
      statistic analysis.
AB  - Methodologies for chemometric classification of five authentic red wine varieties
      from Murfatlar wine center, Romania, young and aged are reported. The
      discriminant analysis based on several anthocyanins, organic acids, (13)C/(12)C,
      (18)O/(16)O and D/H isotopic ratios, (1)H and (13)C NMR fingerprints revealed a
      very satisfactory categorization of the wines, both in terms of variety and
      vintage, thus illustrating the validity of selected variables for wine
      authentication purposes. LDA applied to the combined data shows 85.7%
      classification of wines according to grape variety and 71.1% classification of
      wines according to vintage year, including a control wine set for each
      categorization, thus allowing an accurate interpretation of the data. Thereby,
      anthocyanins, certain anthocyanin ratios, oxalic, shikimic, lactic, citric and
      succinic acids, sugars like glucose, amino acids like histidine, leucine,
      isoleucine and alanine, and also 2,3-butanediol, methanol, glycerol and isotopic
      variables were significant for classification of wines. 

PMID- 26304443
TI  - Adulteration of Argentinean milk fats with animal fats: Detection by fatty acids
      analysis and multivariate regression techniques.
AB  - The aims of the present study were to test the accuracy of the fatty acid ratios
      established by the Argentinean Legislation to detect adulterations of milk fat
      with animal fats and to propose a regression model suitable to evaluate these
      adulterations. For this purpose, 70 milk fat, 10 tallow and 7 lard fat samples
      were collected and analyzed by gas chromatography. Data was utilized to simulate
      arithmetically adulterated milk fat samples at 0%, 2%, 5%, 10% and 15%, for both
      animal fats. The fatty acids ratios failed to distinguish adulterated milk fats
      containing less than 15% of tallow or lard. For each adulterant, Multiple Linear
      Regression (MLR) was applied, and a model was chosen and validated. For that,
      calibration and validation matrices were constructed employing genuine and
      adulterated milk fat samples. The models were able to detect adulterations of
      milk fat at levels greater than 10% for tallow and 5% for lard. 

PMID- 26304444
TI  - Encapsulation artocarpanone and ascorbic acid in O/W microemulsions: Preparation,
      characterization, and antibrowning effects in apple juice.
AB  - The aim of this study is to improve artocarpanone solubility by developing an O/W
      microemulsion with the evaluation of its antibrowning effects. The chemical and
      physical stabilities as well as antibrowning effects in apple juice were also
      evaluated. The formulation of artocarpanone microemulsion consisted of 4% w/w of
      ethyl butyrate, 10.67% w/w of Tween 80, 5.33% w/w of polyethylene glycol 400, and
      80% w/w of water, with a maximum solubility of artocarpanone up to 10.54 +/- 0.01
      mg/mL, at least 3000-folds increase in solubility compared that in water.
      Encapsulating artocarpanone and ascorbic acid (VC) into microemulsion
      simultaneously decreased modest artocarpanone solubility whereas improving its
      stability in long-term storage. Blank, artocarpanone and artocarpanone-Vc-loaded
      microemulsions demonstrated steadily during accelerated and long-term storage.
      Artocarpanone-Vc-loaded microemulsion showed strong antibrowning effects in apple
      juice at room temperature in 24h, suggesting that artocarpanone-Vc-loaded
      microemulsion is a good antibrowning agent for apple juices.

PMID- 26304445
TI  - Cloning, expression, purification and application of a novel chitinase from a
      thermophilic marine bacterium Paenibacillus barengoltzii.
AB  - A novel chitinase gene (PbChi70) from a marine bacterium Paenicibacillus
      barengoltzii was cloned and functionally expressed in Escherichia coli. The
      recombinant enzyme (PbChi70) was purified to homogeneity with a recovery yield of
      51.9%. The molecular mass of purified enzyme was estimated to be 70.0 kDa by SDS
      PAGE. PbChi70 displayed maximal activity at pH 5.5 and 55  degrees C,
      respectively. It exhibited strict substrate specificity for colloidal chitin,
      glycol chitin, powdery chitin, and N-acetyl chitooligosaccharides with degrees of
      polymerization above three. The enzyme exhibited an endo-type cleavage pattern
      and hydrolyzed colloidal chitin to yield mainly (GlcNAc)2. Furthermore, colloidal
      chitin was hydrolyzed by PbChi70 to produce 21.6 mg mL(-1) (GlcNAc)2 with the
      highest conversion yield of 89.5% (w/w). (GlcNAc)2 was further separated by an
      active charcoal column with a purity of 99% and a final yield of 61%. The unique
      enzymatic properties of the chitinase may make it a good candidate for (GlcNAc)2
      production.

PMID- 26304446
TI  - Comments on "Solubility and thermodynamic behavior of vanillin in propane-1,2
      diol+water cosolvent mixtures at different temperatures".

PMID- 26304447
TI  - A comparative study on aromatic profiles of strawberry vinegars obtained using
      different conditions in the production process.
AB  - Impact odorants in strawberry vinegars produced in different containers (glass,
      oak and cherry barrels) were determined by gas chromatography-olfactometry using
      modified frequency (MF) technique, and dynamic headspace gas chromatography-mass
      spectrometry. Aromatic profile of vinegar from strawberry cooked must was also
      studied. All strawberry vinegars retained certain impact odorants from
      strawberries: 3-nonen-2-one, (E,E)-2,4-decadienal, guaiacol, nerolidol,
      pantolactone+furaneol, eugenol, gamma-dodecalactone and phenylacetic acid.
      Isovaleric acid, pantolactone+furaneol, p-vinylguaiacol, phenylacetic acid and
      vanillin were the most important aroma-active compounds in all vinegars. The
      strawberry cooked must vinegar accounted for the highest number of impact
      odorants. Wood barrels provided more aroma complexity than glass containers.
      Impact odorants with grassy characteristics were predominant in vinegar from
      glass containers, and those with sweet and fruity characteristics in vinegars
      from wood barrels. Principal component analysis indicated that the production
      process led to differences in the impact odorants. 

PMID- 26304448
TI  - Voltammetric determination of Pb, Cd, Zn, Cu and Se in milk and dairy products
      collected from Iran: An emphasis on permissible limits and risk assessment of
      exposure to heavy metals.
AB  - This study was carried out to determine the concentrations of some heavy metals
      in dairy products, collected from five industrial regions in Iran (n = 250
      samples) during winter and summer in 2013. The samples were analyzed using the
      differential pulse anodic and cathodic stripping voltammetry technique. The
      obtained ranges of mean Pb, Cd, Cu, Zn and Se were as follow: in raw milk 14.0,
      1.11, 427, 571, 2.19 MUg kg(-1), in pasteurized milk 9.59, 1.0, 378, 447, 1.78
      MUg kg(-1), in cheese 14.5, 1.25, 428, 586, 1.68 MUg kg(-1), in yoghurt 7.54,
      0.99, 399, 431, 1.23 MUg kg(-1) and in doogh 7.2, 0.84, 320, 369, 0.99 MUg kg(
      1), respectively. In nearly all cases the concentrations of the metals were below
      the international permissible limits and do not pose a health concern for the
      consumption of milk and dairy products in Iran.

PMID- 26304449
TI  - Evaluation of umami taste in mushroom extracts by chemical analysis, sensory
      evaluation, and an electronic tongue system.
AB  - Seventeen edible mushrooms commercially available in Korea were analysed for
      their umami taste compounds (5'-nucleotides: AMP, GMP, IMP, UMP, XMP; free amino
      acids: aspartic, glutamic acid) and subjected to human sensory evaluation and
      electronic tongue measurements. Amanita virgineoides featured the highest total
      5'-nucleotide content (36.9 +/- 1.50 mg/g), while monosodium glutamate-like
      components (42.4 +/- 6.90 mg/g) were highest in Agaricus bisporus. The equivalent
      umami concentration (EUC) ranged from 1.51 +/- 0.42 to 3890 +/- 833 mg MSG/g dry
      weight; most mushrooms exhibited a high umami taste. Pleurotus ostreatus scored
      the highest in the human sensory evaluation, while Flammulina velutipes obtained
      the maximum score in the electronic tongue measurement. The EUC and the sensory
      score from the electronic tongue test were highly correlated, and also showed
      significant correlation with the human sensory evaluation score. These results
      suggest that the electronic tongue is suitable to determine the characteristic
      umami taste of mushrooms.

PMID- 26304450
TI  - Bioactive compounds and antioxidant potential fruit of Ximenia americana L.
AB  - The caatinga ecoregion in northeast Brazil presents a wide variety in plant
      species. However, the potential of these species as a source of energy,
      carbohydrates, vitamins, minerals and bioactive properties beneficial to health
      is still unknown. Among these species we can find the wild plum (Ximenia
      americana). Due to its various phytotherapeutic properties and absence of studies
      on the chemical composition of the fruit this article aimed to evaluate the
      bioactive compounds and antioxidant potential of the X. americana in different
      stages of maturation. The fruits of X. americana showed considerable amounts of
      bioactive compounds, as well as antioxidant activity and antioxidant enzymes. The
      fruits at green maturity stage showed higher content of yellow flavonoids (22.07
      mg/100g), anthocyanins (1.92 mg/100 g), polyphenols (3051.62 mg/100 g), starch
      (4.22%), antioxidant activity (489.40 g fruit/g DPPH and 198.77 MUmol Trolox/g)
      and activity of antioxidant enzymes; the antioxidant activity allocated to the
      fruit was shown to be related to the contents of extractable polyphenols, yellow
      flavonoids, total anthocyanins and antioxidant enzymes.

PMID- 26304451
TI  - Effect of alkaline cooking of maize on the content of fumonisins B1 and B2 and
      their hydrolysed forms.
AB  - The effect of nixtamalization on the content of fumonisins (FBs), hydrolysed
      (HFBs) and partially hydrolysed (PHFBs) fumonisins in maize was investigated at
      laboratory-scale. Maize naturally contaminated with FBs and PHFBs was cooked with
      lime. Starting raw maize, steeping and washing waters and final masa fractions
      were analysed for toxin content. Control-cooking experiments without lime were
      also carried out. The nixtamalization reduced the amount of FBs and PHFBs in masa
      and converted them to HFBs. However, the three forms of fumonisins collected in
      all fractions amounted to 183%, indicating that nixtamalization made available
      forms of matrix-associated fumonisins that were then converted to their
      hydrolysed forms. Control-cooking enhanced FBs and PHFBs reduction, due to the
      solubility of fumonisins in water during the steeping process, but did not form
      HFBs. These findings indicate that benefits associated with enhancing the
      nutritional value of nixtamalized maize are also associated with a safer product
      in terms of fumonisin contamination. 

PMID- 26304452
TI  - Identification and characterization of alpha-I-proteinase inhibitor from common
      carp sarcoplasmic proteins.
AB  - Purification of proteinase inhibitor from common carp (Cyprinus carpio)
      sarcoplasmic proteins resulted in 2.8% yield with purification fold of 111. Two
      inhibitors, namely inhibitor I and II, exhibited molecular mass of 47 and 52 kDa,
      respectively, based on non-reducing sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. Both inhibitors I and II were identified to be alpha-1
      proteinase inhibitor (alpha1-PI) based on LC-MS/MS. They were glycoproteins and
      molecular mass after peptide-N-glycosidase F treatment was 38 and 45 kDa,
      respectively. The N-glycosylation sites of both inhibitors were determined to be
      at N214 and N226. The inhibitors specifically inhibited trypsin. The common carp
      alpha1-PI showed high thermal stability with denaturation temperatures of 65.43
      and 73.31  degrees C, which were slightly less than those of ovomucoid. High
      stability toward NaCl was also evident up to 3M. The common carp alpha1-PI
      effectively reduced autolytic degradation of bigeye snapper surimi at the
      concentration as low as 0.025%.

PMID- 26304453
TI  - In vitro amylolysis of pulse and hylon VII starches explained in terms of their
      composition, morphology, granule architecture and interaction between hydrolysed
      starch chains.
AB  - The objective of this study was to understand the factors underlying the
      susceptibility of pulse (lablab bean, navy bean, rice bean, tepary bean, velvet
      bean, and wrinkled pea) and hylon VII starches towards in vitro hydrolysis by the
      combined action of pancreatin and amyloglucosidase. The time taken to reach an
      equivalent level of hydrolysis (50%) varied significantly among the starches.
      Changes to molecular order, crystallinity, double helical content, radial
      orientation of starch chains (polarized light), enthalpy and apparent amylose
      content during the progress of hydrolysis showed that rate and extent of
      hydrolysis were influenced both by the structure of the native starches at
      different levels (molecular, mesoscopic, microscopic) of granule organization,
      and by the extent of retrogradation between hydrolysed starch chains. 

PMID- 26304454
TI  - Anti-glycation properties of the aqueous extract solutions of dried algae
      products and effect of lactic acid fermentation on the properties.
AB  - The antioxidant and anti-glycation properties in aqueous extract solutions (AESs)
      of 11 dried algae products were investigated. AESs of brown algae Ecklonia kurome
      (kurome) and Ecklonia stolonifera (tsuruarame) showed a strong DPPH radical
      scavenging capacity and Fe-reducing power with high total phenolic compound
      content. On the other hand, superoxide anion radical-scavenging capacities of
      Porphyra sp. (iwanori, red alga), sporophyll of Undaria pinnatifida (mekabu,
      brown alga), and Gelidiaceae sp. (tengusa, red alga) were also high. Anti
      glycation activities in BSA-fructose and BSA-methylglyoxal glycation were also
      high in kurome, while iwanori showed high activity. Results of the BSA-fructose
      model agreed with those of superoxide anion radical-scavenging. On the other
      hand, those of the BSA-methylglyoxal model agreed with those of the phenolic
      content, DPPH radical-scavenging capacity, and Fe-reducing power. Anti-glycation
      activities of iwanori, U. pinnatifida (wakame), and mekabu in the BSA-fructose
      model were clearly increased by fermentation with Lactobacillus plantarum AN6. 

PMID- 26304455
TI  - Applicability of salt reduction strategies in pizza crust.
AB  - In an effort to reduce population-wide sodium intake from processed foods, due to
      major health concerns, several different strategies for sodium reduction in pizza
      crust without any topping were evaluated by sensory analyses. It was possible to
      reduce sodium by 10% in one single step or to replace 30% of NaCl by KCl without
      a noticeable loss of salty taste. The late addition of coarse-grained NaCl
      (crystal size: 0.4-1.4 mm) to pizza dough led to an enhancement of saltiness
      through taste contrast and an accelerated sodium delivery measured in the mouth
      and in a model mastication simulator. Likewise, the application of an aqueous
      salt solution to one side of the pizza crust led to an enhancement of saltiness
      perception through faster sodium availability, leading to a greater contrast in
      sodium concentration. Each of these two strategies allowed a sodium reduction of
      up to 25% while maintaining taste quality.

PMID- 26304456
TI  - Determination of a selection of synthetic cannabinoids and metabolites in urine
      by UHPSFC-MS/MS and by UHPLC-MS/MS.
AB  - Two different analytical techniques, ultra-high performance supercritical fluid
      chromatography-tandem mass spectrometry (UHPSFC-MS/MS) and reversed phase ultra
      high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS),
      were used for the determination of two synthetic cannabinoids and eleven
      metabolites in urine; AM-2201 N-4-OH-pentyl, AM-2233, JWH-018 N-5-OH-pentyl, JWH
      018 N-pentanoic acid, JWH-073 N-4-OH-butyl, JWH-073 N-butanoic acid, JWH-122 N-5
      OH-pentyl, MAM-2201, MAM-2201 N-4-OH-pentyl, RCS-4 N-5-OH-pentyl, UR-144
      degradant N-pentanoic acid, UR-144 N-4-OH-pentyl, and UR-144 N-pentanoic acid.
      Sample preparation included a liquid-liquid extraction after deconjugation with
      beta-glucuronidase. The UHPSFC-MS/MS method used an Acquity UPC(2 TM) BEH column
      with a mobile phase consisting of CO2 and 0.3% ammonia in methanol, while the
      UHPLC-MS/MS method used an Acquity UPLC(r) BEH C18 column with a mobile phase
      consisting of 5 mM ammonium formate (pH 10.2) and methanol. MS/MS detection was
      performed with positive electrospray ionization and two multiple reaction
      monitoring transitions. Deuterated internal standards were used for six of the
      compounds. Limits of quantification (LOQs) were between 0.04 and 0.4 ug/L.
      Between-day relative standard deviations at concentrations >= LOQ were <=20%,
      with biases within +/-19%. Recoveries ranged from 40 to 90%. Corrected matrix
      effects were within 100 +/- 10%, except for MAM-2201 with UHPSFC-MS/MS, and for
      UR-144 N-pentanoic acid and MAM-2201 N-4-OH-pentyl with UHPLC-MS/MS. Elution
      order obtained by UHPSFC-MS/MS was almost opposite to that obtained by UHPLC
      MS/MS, making this instrument setup an interesting combination for screening and
      confirmation analyses in forensic cases. The UHPLC-MS/MS method has, since August
      2014, been successfully used for confirmation of synthetic cannabinoids in urine
      samples revealing a positive immunoassay screening result. Copyright (c) 2015
      John Wiley & Sons, Ltd. 

PMID- 26304457
TI  - Investigation of VOCs associated with different characteristics of breast cancer
      cells.
AB  - The efficacy of breath volatile organic compounds (VOCs) analysis for the
      screening of patients bearing breast cancer lesions has been demonstrated by
      using gas chromatography and artificial olfactory systems. On the other hand, in
      vitro studies suggest that VOCs detection could also give important indications
      regarding molecular and tumorigenic characteristics of tumor cells. Aim of this
      study was to analyze VOCs in the headspace of breast cancer cell lines in order
      to ascertain the potentiality of VOCs signatures in giving information about
      these cells and set-up a new sensor system able to detect breast tumor-associated
      VOCs. We identified by Gas Chromatography-Mass Spectrometry analysis a VOCs
      signature that discriminates breast cancer cells for: i) transformed condition;
      ii) cell doubling time (CDT); iii) Estrogen and Progesterone Receptors (ER, PgR)
      expression, and HER2 overexpression. Moreover, the signals obtained from a
      temperature modulated metal oxide semiconductor gas sensor can be classified in
      order to recognize VOCs signatures associated with breast cancer cells, CDT and
      ER expression. Our results demonstrate that VOCs analysis could give clinically
      relevant information about proliferative and molecular features of breast cancer
      cells and pose the basis for the optimization of a low-cost diagnostic device to
      be used for tumors characterization. 

PMID- 26304459
TI  - Delivery room end tidal CO2 monitoring in preterm infants <32 weeks.
AB  - OBJECTIVES: To determine the feasibility of end tidal (EtCO2) monitoring of
      preterm infants in the delivery room, to determine EtCO2 levels during delivery
      room stabilisation, and to examine the incidence of normocapnia (5-8 kPa) on
      admission to the neonatal intensive care unit in the EtCO2 monitored group
      compared with a historical cohort without EtCO2 monitoring. PATIENTS AND METHODS:
      Preterm infants (<32 weeks) were eligible for inclusion in this observational
      study. The evolution of EtCO2 values immediately after delivery was assessed and
      linear least-squares methods were used to fit a line to EtCO2 recordings. The
      partial pressure of CO2 in blood (PCO2) from the infants who received EtCO2
      monitoring was compared with a historical cohort without EtCO2 monitoring.
      RESULTS: EtCO2 monitoring was feasible in the delivery room. EtCO2 values were
      successfully obtained in 39 (88.7%) of the 44 infants included in the study.
      EtCO2 gradually increased over the first 4 min. Intubated infants had higher
      EtCO2 values compared with infants who were not intubated, with median (IQR)
      values of 4.7 (3.3-8.4) kPa versus 3.2 (2.6-4.2) kPa (p=0.05). No difference was
      found between the proportions of PCO2 values within the range of normocapnia
      among infants who received EtCO2 monitoring compared with those who did not
      (56.8% vs 47.9%, p=0.396). CONCLUSIONS: Delivery room EtCO2 monitoring is
      feasible and safe. EtCO2 values obtained after birth reflect the establishment of
      functional residual capacity and effective ventilation. The potential short-term
      and long-term consequences of EtCO2 monitoring should be established in
      randomised controlled trials.

PMID- 26304460
TI  - Neurodevelopmental outcome in very low birthweight infants with pathological
      umbilical artery flow.
AB  - OBJECTIVE: To assess neurodevelopmental outcome during toddlerhood in very low
      birthweight (VLBW) infants with absent or reverse end-diastolic flow (AREDF) in
      the umbilical artery (UA) during pregnancy. DESIGN: Retrospective cohort study
      with matched control group. SETTING: Tertiary perinatal centre. PATIENTS AND
      OUTCOME MEASURES: We compared longitudinally collected data on neonatal and
      neurodevelopmental outcomes among 41 infants born in our institution from 1997 to
      2010 with birth weight <1500 g and UA AREDF and 41 infants with prenatally normal
      UA Doppler parameters matched for gestational age, birth weight, sex and year of
      birth. We evaluated neurodevelopmental outcome at a median (range) corrected age
      of 23.3 (10.1-29.6) months using the Bayley scales of infant development, 2nd
      edition (BSID-II), and neurological examination. RESULTS: The mental development
      index in UA AREDF children (median (range) 84 (49-116)) was significantly lower
      than in controls (median (range) 91 (62-140)), including after adjustment for
      confounders. Intergroup differences in psychomotor development index (PDI; BSID
      II) and the rate of cerebral palsy or minor neuromotor dysfunction were non
      significant. CONCLUSIONS: VLBW infants with UA AREDF have a higher risk of poorer
      mental development during toddlerhood than controls matched for gestational age,
      birth weight, sex and year of birth. UA AREDF may be considered a prenatal
      predictor of poorer mental development in this population. Long-term follow-up
      studies with larger cohorts are needed to better evaluate the impact of this
      prenatal factor on later neurodevelopment.

PMID- 26304458
TI  - Mice repeatedly exposed to Group-A beta-Haemolytic Streptococcus show
      perseverative behaviors, impaired sensorimotor gating, and immune activation in
      rostral diencephalon.
AB  - Repeated exposure to Group-A beta-Haemolytic Streptococcus (GAS) may constitute a
      vulnerability factor in the onset and course of pediatric motor disturbances. GAS
      infections/colonization can stimulate the production of antibodies, which may
      cross the blood brain barrier, target selected brain areas (e.g. basal ganglia),
      and exacerbate motor alterations. Here, we exposed developing SJL male mice to
      four injections with a GAS homogenate and evaluated the following domains: motor
      coordination; general locomotion; repetitive behaviors; perseverative responses;
      and sensorimotor gating (pre-pulse inhibition, PPI). To demonstrate that
      behavioral changes were associated with immune-mediated brain alterations, we
      analyzed, in selected brain areas, the presence of infiltrates and microglial
      activation (immunohistochemistry), monoamines (HPLC), and brain metabolites (in
      vivo Magnetic Resonance Spectroscopy). GAS-exposed mice showed increased
      repetitive and perseverative behaviors, impaired PPI, and reduced concentrations
      of serotonin in prefrontal cortex, a brain area linked to the behavioral domains
      investigated, wherein they also showed remarkable elevations in lactate. Active
      inflammatory processes were substantiated by the observation of infiltrates and
      microglial activation in the white matter of the anterior diencephalon. These
      data support the hypothesis that repeated GAS exposure may elicit inflammatory
      responses in brain areas involved in motor control and perseverative behavior,
      and result in phenotypic abnormalities. 

PMID- 26304461
TI  - Lower rate of selected congenital heart defects with better maternal diet
      quality: a population-based study.
AB  - OBJECTIVE: To evaluate whether better diet quality in mothers is associated with
      lower risk for major non-syndromic congenital heart defects in their children.
      DESIGN: Multicentre population-based case-control study, the National Birth
      Defects Prevention Study. SETTING: Ten sites in the USA. PARTICIPANTS: Mothers of
      babies with major non-syndromic congenital heart defects (n=9885) and mothers
      with unaffected babies (n=9468) with estimated date of delivery from 1997 to
      2009. MAIN OUTCOME MEASURES: Adjusted ORs for specific major congenital heart
      defects by quartiles of maternal diet quality in the year before pregnancy,
      assessed by the Diet Quality Index for pregnancy (DQI-P) and the Mediterranean
      Diet Score. Quartile 1 (Q1) reflecting the worst diet quality and Q4 the best
      diet quality. RESULTS: Better diet quality was associated with reduced risk for
      some conotruncal and atrial septal heart defects. For DQI-P, estimated risks
      reductions (Q4 vs Q1) for conotruncal defects were 37% for tetralogy of Fallot
      (OR 0.63, 95% CI 0.49 to 0.80) and 24% overall (OR 0.76, 95% CI 0.64 to 0.91);
      and for septal defects, 23% for atrial septal defects (OR 0.77, 95% CI 0.63 to
      0.94) and 14% overall (OR 0.86, 95% CI 0.75 to 1.00). Risk reductions were weaker
      or minimal for most other major congenital heart defects. CONCLUSIONS: Better
      diet quality is associated with a reduced occurrence of some conotruncal and
      septal heart defects. This finding suggests that a reduction in certain cardiac
      malformations may be an additional benefit of improved maternal diet quality,
      reinforcing current preconception care recommendations.

PMID- 26304462
TI  - Anderson attractors in active arrays.
AB  - In dissipationless linear media, spatial disorder induces Anderson localization
      of matter, light, and sound waves. The addition of nonlinearity causes
      interaction between the eigenmodes, which results in a slow wave diffusion. We go
      beyond the dissipationless limit of Anderson arrays and consider nonlinear
      disordered systems that are subjected to the dissipative losses and energy
      pumping. We show that the Anderson modes of the disordered Ginsburg-Landau
      lattice possess specific excitation thresholds with respect to the pumping
      strength. When pumping is increased above the threshold for the band-edge modes,
      the lattice dynamics yields an attractor in the form of a stable multi-peak
      pattern. The Anderson attractor is the result of a joint action by the pumping
      induced mode excitation, nonlinearity-induced mode interactions, and dissipative
      stabilization. The regimes of Anderson attractors can be potentially realized
      with polariton condensates lattices, active waveguide or cavity-QED arrays. 

PMID- 26304464
TI  - Effects of calcium supplementation on biomarkers of inflammation and oxidative
      stress in colorectal adenoma patients: a randomized controlled trial.
AB  - Inflammation and oxidative stress play important roles in colorectal
      carcinogenesis. There is strong evidence that calcium reduces risk for colorectal
      neoplasms, possibly through its ability to bind bile acids and prevent their
      colonic toxicity (which occurs via an oxidative mechanism and results in an
      inflammatory response). In a previously reported pilot, randomized, controlled
      trial among sporadic colorectal adenoma patients we found that those on 2.0 g/day
      of calcium, relative to those on placebo, had an estimated drop in a combined
      cytokine z-score of 48% (P = 0.18) over 6 months. To follow-up these promising
      preliminary findings, we tested the efficacy of two doses of supplemental calcium
      (1.0 or 2.0 g/day) relative to placebo on modulating circulating biomarkers of
      inflammation [C-reactive protein (CRP) and 10 cytokines] and oxidative stress (F2
      isoprostanes) over a 4-month treatment period among 193 patients with previous
      sporadic, colorectal adenoma in a randomized, double-blinded, placebo-controlled
      clinical trial. The inflammation markers were measured in plasma using
      electrochemiluminescence detection-based immunoassays, and F2-isoprostanes were
      measured in plasma using gas chromatography-mass spectrometry. Over a 4-month
      treatment period, we found no appreciable effects of calcium on CRP, cytokines,
      or F2-isoprostanes (P > 0.4), overall or within strata of several major risk
      factors for colorectal carcinogenesis, such as body mass index and regular use of
      nonsteroidal anti-inflammatory drugs. Overall, our results provide no evidence
      that calcium supplementation favorably modulates concentrations of circulating
      biomarkers of inflammation or oxidative stress over 4 months among patients with
      a previous colorectal adenoma.

PMID- 26304463
TI  - Paired box 5 methylation detection by droplet digital PCR for ultra-sensitive
      deep surgical margins analysis of head and neck squamous cell carcinoma.
AB  - Molecular deep surgical margin analysis has been shown to predict locoregional
      recurrences of head and neck squamous cell carcinoma (HNSCC). To improve the
      accuracy and versatility of the analysis, we used a highly tumor-specific
      methylation marker and highly sensitive detection technology to test DNA from
      surgical margins. Histologically cancer-negative deep surgical margin samples
      were prospectively collected from 82 eligible HNSCC surgeries by an imprinting
      procedure (n = 75) and primary tissue collection (n = 70). Bisulfite-treated DNA
      from each sample was analyzed by both conventional quantitative methylation
      specific PCR (QMSP) and QMSP by droplet digital PCR (ddQMSP) targeting Paired box
      5 (PAX5) gene promoter methylation. The association between the presence of PAX5
      methylation and locoregional recurrence-free survival (LRFS) was evaluated. PAX5
      methylation was found in 68.0% (51 of 75) of tumors in the imprint samples and
      71.4% (50 of 70) in the primary tissue samples. Among cases that did not have
      postoperative radiation (n = 31 in imprint samples, n = 29 in tissue samples),
      both conventional QMSP and ddQMSP revealed that PAX5 methylation-positive margins
      was significantly associated with poor LRFS by univariate analysis. In
      particular, ddQMSP increased detection of the PAX5 marker from 29% to 71% in the
      nonradiated imprint cases. Also, PAX5 methylated imprint margins were an
      excellent predictor of poor LRFS [HR, 3.89; 95% confidence interval (CI), 1.19
      17.52; P = 0.023] by multivariate analysis. PAX5 methylation appears to be an
      excellent tumor-specific marker for molecular deep surgical margin analysis of
      HNSCC. Moreover, the ddQMSP assay displays increased sensitivity for methylation
      marker detection.

PMID- 26304465
TI  - PAK1 promotes intestinal tumor initiation.
AB  - p21-activated kinase 1 (PAK1) is a serine/threonine kinase that is overexpressed
      in colorectal cancer. PAK1 is a target of mesalamine [5-aminosylicylic acid (5
      ASA)], a common drug for the treatment of ulcerative colitis with prospective
      chemopreventive properties. Here, we investigated whether PAK1 deletion impedes
      tumorigenesis in murine intestinal cancer models. Ten-week-old APC(min) or
      APC(min)/PAK1(-/-) mice were monitored for 8 weeks, euthanized, and assessed for
      tumor number and size. Six- to 8-week-old PAK1(-/-) and wild-type (WT) mice
      received one 10 mg/kg intraperitoneal injection of azoxymethane (AOM) and four
      cycles of 1.7% dextran sodium sulfate (DSS) for 4 days followed by 14 days of
      regular water. Mice also received 5-ASA via diet. Tumor incidence and size was
      assessed via colonoscopy and pathology. Molecular targets of PAK1 and 5-ASA were
      evaluated via immunohistochemistry (IHC) in both models. PAK1 deletion reduced
      tumor multiplicity and tumor burden but did not alter average tumor size in
      APC(min) mice. IHC revealed that PAK1 deletion reduced p-AKT, beta-catenin, and c
      Myc expression in APC(min) adenomas. Colonoscopy and pathologic analysis revealed
      that PAK1 deletion reduced tumor multiplicity without affecting tumor size in
      AOM/DSS-treated mice. 5-ASA treatment and PAK1 deletion impeded tumor
      multiplicity and dysplastic lesions in AOM/DSS mice. IHC further revealed that 5
      ASA blocked beta-catenin signaling via inhibition of PAK1/p-AKT. These data
      indicate that PAK1 contributes to initiation of intestinal carcinogenesis.

PMID- 26304467
TI  - Hydrogel Templates for Rapid Manufacturing of Bioactive Fibers and 3D Constructs.
AB  - Hydrogel templates are formed to entrap various pre-polymers prior to their
      crosslinking process. Upon the completion of the crosslinking process, an
      independent polymer network with the same fiber geometry is formed. The hydrogel
      template can be removed if necessary. As the proof-of-principle, fibers from
      various polymers are fabricated. The fabricated hybrid polymeric fibers are
      bioactive and can be bioprinted or assembled using textile processes. The
      approach can be used for creating complex 3D constructs for various applications.

PMID- 26304466
TI  - Urinary metabolites of prostanoids and risk of recurrent colorectal adenomas in
      the Aspirin/Folate Polyp Prevention Study (AFPPS).
AB  - Aspirin has been shown to protect against colorectal neoplasms; however, the
      optimal chemopreventive dose and underlying mechanisms are unclear. We aimed to
      study the relationship between prostanoid metabolites and aspirin's effect on
      adenoma occurrence. We used data from the Aspirin/Folate Polyp Prevention Study,
      in which 1,121 participants with a recent adenoma were randomized to placebo or
      two doses of aspirin (81 or 325 mg/d) to be taken until the next surveillance
      colonoscopy, anticipated about 3 years later. Urinary metabolites of prostanoids
      (PGE-M, PGI-M, and dTxB2) were measured using liquid chromatography/mass
      spectrometry or GC/NICI-MS in 876 participants near the end of treatment follow
      up. Poisson regression with a robust error variance was used to calculate
      relative risks and 95% confidence intervals. PGE-M, PGI-M, and dTxB2 levels were
      28%, 37%, and 60% proportionately lower, respectively, in individuals who took
      325 mg of aspirin compared with individuals who took placebo (all P < 0.001).
      Similarly, among individuals who took 81 mg of aspirin, PGE-M, PGI-M, and dTxB2
      were, respectively, 18%, 30%, and 57% proportionally lower compared with placebo
      (all P < 0.005). None of the metabolites or their ratios were statistically
      significantly associated with the risk of adenoma occurrence. The effect of
      aspirin in reducing adenoma risk was independent of prostanoid levels. Aspirin
      use is associated with lower levels of urinary prostanoid metabolites. However,
      our findings do not support the hypothesis that these metabolites are associated
      with adenoma occurrence, suggesting that COX-dependent mechanisms may not
      completely explain the chemopreventive effect of aspirin on colorectal neoplasms.

PMID- 26304468
TI  - Ethnicity and immunization coverage among schools in Israel.
AB  - OBJECTIVE: Recent years have seen a global trend of declining immunization rates
      of recommended vaccines that is more pronounced among school-age children. Ethnic
      disparities in child immunization rates have been reported in several countries.
      We investigated an effect of ethnicity on the vaccination rates of immunizations
      routinely administered within schools in Israel. DESIGN: Data were collected from
      the Ministry of Health database regarding immunization coverage for all
      registered Israeli schools (3736) in the years 2009-2011. Negative binomial
      regression was used to assess the association between school ethnicity and
      immunization coverage while controlling for school characteristics. RESULTS: The
      lowest immunization coverage was found in Bedouin schools (median values of
      75.1%, 81.5% and 0% for the first, second and eighth grades, respectively) in
      2011. During this year, vaccination coverage in the first and second grades in
      Jewish schools was 1.51 and 1.35 times higher, respectively, compared to Bedouin
      schools. In the years 2009 and 2010, no significant increase in risk for lower
      vaccination rate was observed in Bedouin schools, and children in Arab and Druze
      schools were more likely to have been vaccinated. CONCLUSION: The lower
      vaccination refusal rate found in Bedouin schools supports the hypothesis that
      difficulties related to accessibility constitute the main problem rather than
      noncompliance with the recommended vaccination protocol for school-age children,
      featuring higher socio-economic status groups. Our study emphasizes the
      importance of identifying, beyond the national-level data, subpopulation groups
      at risk for non-vaccination. This knowledge is essential to administrative-level
      policy-makers for the allocation of resources and the planning of intervention
      programs.

PMID- 26304469
TI  - An uncommon source of upper gastrointestinal bleeding: epiphrenic esophageal
      diverticulum.
AB  - Esophageal diverticula are rare findings that have an estimated incidence of 1
      per 500 000 people per year, even though acute upper gastrointestinal bleeding is
      a relatively common medical emergency with an incidence of up to 150 per 100 000
      people per year and a mortality rate of 7-14%. An 83-year-old man presented with
      hematemesis and melena. Urgent upper endoscopy revealed an esophageal
      diverticulum, within which was an adherent clot. Removal of the clot identified a
      bleeding vessel within the diverticulum; this was successfully clipped and
      hemostasis was achieved. To the best of our knowledge, this is the first case
      report of a bleeding epiphrenic esophageal diverticulum that was successfully
      managed endoscopically with hemostatic clips alone. While rare, our case serves
      as a reminder that bleeding epiphrenic esophageal diverticula can present as
      massive upper gastrointestinal bleeding and urgent endoscopic therapy can be life
      saving.

PMID- 26304471
TI  - Dealing with modularity of multibody models.

PMID- 26304470
TI  - Fine needle aspiration of secondary synovial sarcoma of the thyroid gland.
AB  - Synovial sarcomas (SS) of the head and neck region are extremely rare and arise
      in only 5% of cases. We present a case of secondary SS of the thyroid originally
      diagnosed as medullary carcinoma on fine needle aspiration (FNA). A 41-year-old
      man presented with several weeks of dysphonia and a left thyroid mass. FNA of the
      thyroid nodule showed a cellular smear composed of loosely cohesive oval to
      spindle-shaped cells with irregular nuclear borders, finely granular chromatin,
      and inconspicuous nucleoli. The patient was diagnosed with medullary carcinoma
      and underwent a total thyroidectomy. Intro-operatively, the mass was found to
      arise from the tracheoesophageal groove with spread to the left thyroid.
      Microscopic examination of the thyroid tumor revealed a dense spindle cell
      proliferation with abundant mitoses, scant cords and nests of epithelial cells
      and foci of necrosis. The spindle cells were positive for bcl2 and vimentin and
      the epithelial cells were positive for cytokeratin 8/18 and epithelial membrane
      antigen (EMA). Both spindle and epithelial cells were negative for thyroglobulin,
      calcitonin, synaptophysin and chromogranin. Fluorescence in situ hybridization
      (FISH) demonstrated translocation (X;18)(p11;q11), confirming the diagnosis of
      SS. The patient underwent a total laryngopharyngoesophagectomy with subsequent
      adjuvant therapy and is currently disease free. Only 6 cases of histologically
      confirmed primary SS of the thyroid have been reported. To the best of our
      knowledge, this is the first case of FISH-confirmed secondary SS of the thyroid
      and also the first case of SS arising from the tracheoesophageal groove.

PMID- 26304472
TI  - Achromatopsia: on the doorstep of a possible therapy.
AB  - Achromatopsia (ACHM) is a rare autosomal recessive inherited retinal disorder
      with an incidence of approximately 1 in 30,000. It presents at birth or early
      infancy and is typically characterized by reduced visual acuity, nystagmus,
      photophobia, and very poor or absent color vision. The symptoms arise from
      isolated cone dysfunction, which can be caused by mutations in the crucial
      components of the cone phototransduction cascade. Although ACHM is considered a
      functionally nonprogressive disease affecting only the cone system, recent
      studies have described progressive age-dependent changes in retinal architecture.
      Currently, no specific therapy is available for ACHM; however, gene replacement
      therapy performed on animal models for three ACHM genes has shown promising
      results. Accurate genetic and clinical diagnosis of patients may therefore
      enhance and enable therapeutic intervention in the near future. This short review
      summarizes the genetic background, pathophysiology, clinical findings,
      diagnostics, and therapeutic perspectives in ACHM.

PMID- 26304473
TI  - Chondrosarcoma of the hyoid bone: A diagnostic pitfall in the submandibular
      region.
AB  - Chondrosarcoma is a malignant chondroid matrix-producing neoplasm which usually
      presents in the bones of the pelvis, followed by the proximal femur, proximal
      humerus, distal femur and ribs. The occurrence of this lesion in the hyoid bone
      is exceedingly rare, with only a few reported cases, and its diagnosis by fine
      needle aspiration cytology (FNAC) in this particular location, to our knowledge,
      has never been addressed. Furthermore, the sampling of chondroid matrix at this
      site can pose a diagnostic dilemma with other lesions of the submandibular
      region. This report describes the clinical, radiologic and cytologic features on
      FNAC of a chondrosarcoma of the hyoid bone, emphasizing the diagnostic pitfalls
      of this entity and expanding the cytologic differential diagnosis of tumors of
      the submandibular region.

PMID- 26304474
TI  - The concept of frozen elastic energy as a consequence of changes in
      microstructure morphology.

PMID- 26304475
TI  - Assessment of the Mechanistic Role of Cinnarizine in Modulating Experimentally
      Induced Bronchial Asthma in Rats.
AB  - BACKGROUND/AIMS: Calcium influx, inflammatory infiltration, cytokine production,
      immunoglobulin E activation and oxidative stress play coordinated roles in
      bronchial asthma pathogenesis. We aim to assess the protective effect of
      cinnarizine against experimentally induced bronchial asthma. METHODS: Bronchial
      asthma was induced by ovalbumin sensitization and challenge. Rats were allocated
      into a normal control, an asthma control, a dexamethasone (standard) treatment,
      and 2 cinnarizine treatment groups. The respiratory functions tidal volume (TV)
      and peak expiratory flow rate (PEFR), the inflammatory cytokines tumor necrosis
      factor-alpha (TNF-alpha) and interleukin-5 (IL-5) in lung tissue, the allergic
      immunoglobulin IgE in serum, the absolute eosinophil count (AEC) in
      bronchoalveolar lavage fluid (BALF), as well as the oxidative and nitrosative
      markers glutathione reduced (GSH) and superoxide dismutase (SOD) in lung tissue
      and nitric oxide end products (NOx) in BALF were assessed, followed by a
      histopathological study. RESULTS: Cinnarizine administration significantly
      restored TV, PEFR, TNF-alpha, IL-5, IgE, AEC, GSH, SOD and NOx values back to
      normal levels, and significantly decreased perivascular and peribronchiolar
      inflammatory scores. CONCLUSION: Cinnarizine may protect against experimental
      bronchial asthma. Suppressant effect of cinnarizine on pro-inflammatory cytokines
      release, IgE antibody production, eosinophil infiltration as well as oxidative
      and nitrosative stress may explain its anti-asthmatic potential.

PMID- 26304476
TI  - Mechanisms of behavioural maintenance: Long-term effects of theory-based
      interventions to promote safe water consumption.
AB  - Theory-based interventions can enhance people's safe water consumption, but the
      sustainability of these interventions and the mechanisms of maintenance remain
      unclear. We investigated these questions based on an extended theory of planned
      behaviour. Seven hundred and ten (445 analysed) randomly selected households
      participated in two cluster-randomised controlled trials in Bangladesh. Study 1
      promoted switching to neighbours' arsenic-safe wells, and Study 2 promoted
      switching to arsenic-safe deep wells. Both studies included two intervention
      phases. Structured interviews were conducted at baseline (T1), and at 1-month
      (T2), 2-month (T3) and 9-month (T4) follow-ups. In intervention phase 1 (between
      T1 and T2), commitment-based behaviour change techniques--reminders,
      implementation intentions and public commitment--were combined with information
      and compared to an information-only control group. In phase 2 (between T2 and
      T3), half of each phase 1 intervention group was randomly assigned to receive
      either commitment-based techniques once more or coping planning with reminders
      and information. Initial well-switching rates of up to 60% significantly declined
      by T4: 38.3% of T2 safe water users stopped consuming arsenic-safe water. The
      decline depended on the intervention. Perceived behavioural control, intentions,
      commitment strength and coping planning were associated with maintenance. In line
      with previous studies, the results indicate that commitment and reminders
      engender long-term behavioural change.

PMID- 26304477
TI  - Invited commentary.

PMID- 26304478
TI  - Invited commentary.

PMID- 26304479
TI  - Ex vivo repair of renal artery aneurysms.
AB  - OBJECTIVE: Renal artery aneurysms (RAAs) are rare but remain challenging lesions
      when treatment is required. Endovascular techniques may be useful in selected,
      more proximal lesions with amenable morphology, but open surgical repair is often
      required for more distal, anatomically complex hilar RAAs that often have several
      branches and unfavorable anatomy. This study reviewed a single-center experience
      with ex vivo repair of 14 of these more complex, distal RAAs. METHODS: The
      records of 14 consecutive patients having ex vivo RAA repair between 1997 and
      2013 were retrospectively reviewed. Demographic data, operative details, and
      blood pressure and renal function status were recorded. Graft patency was
      observed with renal duplex sonography. RESULTS: Fourteen hilar RAAs were repaired
      in 10 women and 4 men with a mean age of 54 years. Hypertension was present in 12
      (86%). Preoperative renal dysfunction was present in two (14%). Aneurysm size
      averaged 2.9 cm. Six RAAs (43%) were symptomatic with flank or abdominal pain. Ex
      vivo repair was performed in all cases with use of saphenous vein for renal-renal
      bypass. No patient had pelvic autotransplantation or concomitant aortic
      reconstruction. Ex vivo RAA repair was technically successful in 12 cases; two
      patients required nephrectomy. Two patients with pre-existing renal insufficiency
      had improvement postoperatively, but hypertension was clinically unchanged in all
      patients. No patient required postoperative dialysis. Duplex sonography
      documented continued graft patency in the 12 technically successful cases during
      a mean follow-up of 19 months. CONCLUSIONS: Open ex vivo surgical repair with
      renal-renal bypass is a successful and durable treatment for complex distal RAAs
      that require repair. These procedures had low morbidity and mortality and an
      acceptable rate of renal function preservation. Blood pressure control in these
      patients did not change significantly after RAA repair.

PMID- 26304480
TI  - Carotid artery stenting may be performed safely in patients with radiation
      therapy-associated carotid stenosis without increased restenosis or target lesion
      revascularization.
AB  - OBJECTIVE: Neck radiation therapy (XRT) can induce carotid artery stenosis and
      may increase the technical difficulty of endarterectomy. It is considered a
      relative indication for carotid angioplasty and carotid artery stenting (CAS).
      This study sought to evaluate differences in CAS embolic potential and restenosis
      performed on XRT and non-XRT patients. METHODS: At three institutions, 366 CAS
      procedures were performed on 321 patients (XRT, n = 43; non-XRT, n = 323). Mean
      follow-up was 410 days (median, 282 days; range, 7-1920 days). Patients were
      observed with duplex ultrasound to assess for restenosis. Additional end points
      included target lesion revascularization (TLR), myocardial and cerebrovascular
      events, and perioperative complications. Captured particulate from embolic
      protection filters was analyzed with photomicroscopy and image analysis software
      for 27 XRT and 214 non-XRT filters. RESULTS: XRT patients were more likely to be
      male and had lower rates of hypertension, coronary artery disease, and diabetes
      mellitus, although the mean age at procedure did not differ. There was no
      increase in severe internal carotid tortuosity among XRT patients (XRT: 50% vs
      non-XRT: 34.7%; P = .06). Indication for CAS did not differ between the two
      groups, including the number of CAS procedures performed for symptomatic carotid
      stenosis (XRT: 39.7% vs non-XRT: 39.0%; P = NS). Perioperative outcomes,
      including the composite 30-day stroke, myocardial infarction, and mortality, were
      not significantly different (XRT: 2.6% vs non-XRT: 3.9%; P = NS.) There were no
      significant differences in restenosis rate at the 50% (XRT: 9.4% vs non-XRT:
      8.6%; P = NS) or 70% (XRT: 3.5% vs non-XRT: 8.6%; P = NS) threshold. Filter
      particle analysis revealed that filters from XRT patients had more numerous large
      particles per filter (1.4 vs 0.7; P < .05) and larger mean particle size (464.1
      MUm vs 320.0 MUm; P < .05). TLR did not differ significantly between the groups.
      CONCLUSIONS: In contrast to earlier studies, this analysis reveals that there are
      significant differences in XRT and non-XRT patients undergoing CAS in terms of
      medical comorbidities and embolic material captured in embolic protection
      filters. The decreased incidence of atherosclerotic risk factors was observed in
      XRT patients probably because XRT was the primary factor responsible for carotid
      stenosis. Despite increased embolic particle size, CAS can be performed safely
      with no increased morbidity, TLR, or restenosis in XRT patients.

PMID- 26304481
TI  - Autologous bone marrow mononuclear cell implantation therapy is an effective limb
      salvage strategy for patients with severe peripheral arterial disease.
AB  - OBJECTIVE: This study was conducted to determine if intramuscular and intra
      arterial stem cell injections delay or prevent major limb amputations, improve
      ankle-brachial index measurements, relieve rest pain, and improve ulcer healing.
      METHODS: A prospective case series with interventions occurring between December
      2007 and September 2012 and a 3-month minimum follow-up was conducted at an urban
      tertiary care referral hospital. Patients with severe limb-threatening peripheral
      arterial disease, without other options for revascularization, were eligible for
      enrollment. Dual intramuscular and intra-arterial injection of bone marrow
      mononuclear cells harvested from the iliac crest was performed. Major limb
      amputation at 3 months was the primary outcome measure. Secondary outcome
      measures included ankle-brachial index measurements, rest pain, and ulceration
      healing. Kaplan-Meier survivorship was performed to ascertain overall
      survivorship of the procedure. RESULTS: No complications related to the procedure
      were reported. Of 49 patients (56 limbs) enrolled, two patients (two limbs) died,
      but had not undergone major amputation, and five limbs (8.9%) underwent major
      amputation within the first 3 months. Three-month follow-up evaluations were
      conducted on the remaining 49 limbs (42 patients). Median postprocedure revised
      Rutherford and Fontaine classifications were significantly lower compared with
      median baseline classifications. After 3 months, seven patients (nine limbs) died
      but had not undergone major amputation, and seven limbs (14.3%) underwent major
      amputation. At a mean follow-up of 18.2 months, the remaining 33 limbs (29
      patients) had not undergone a major amputation. Freedom from major adverse limb
      events (MALE) was 91.1% (95% confidence interval, 79.9-96.2) at 3 months and
      75.6% (95% confidence interval, 59.4-86.1) at 12 months. CONCLUSIONS: This
      procedure was designed to improve limb perfusion in an effort to salvage limbs in
      patients for whom amputation was the only viable treatment option. The results of
      this analysis indicate that it is an effective strategy for limb salvage for
      patients with severe peripheral arterial disease.

PMID- 26304482
TI  - Gender differences following supervised exercise therapy in patients with
      intermittent claudication.
AB  - OBJECTIVE: Prevalence of peripheral arterial disease is equal in men and women.
      However, women seem to suffer more from the burden of disease. Current studies on
      gender-related outcomes following supervised exercise therapy (SET) for
      intermittent claudication (IC) yield conflicting results. METHODS: A follow-up
      analysis was performed on data from the 2010 Exercise Therapy in Peripheral
      Arterial Disease (EXITPAD) study, a multicenter randomized controlled trial
      including IC patients receiving SET or a walking advice. The SET program was
      supervised by physiotherapists and included interval-based treadmill walking
      approximating maximal pain combined with activities such as cycling and rowing.
      Patients usually started with three 30-minute sessions a week. Training frequency
      was adapted during the following year on the basis of individual needs. The
      primary outcome was gender differences regarding the change in absolute
      claudication distance (ACD) after SET. ACD was defined as the number of meters
      that a patient had covered just before he or she was forced to stop walking
      because of intolerable pain. Secondary outcomes were gender differences in change
      of functional walking distance, quality of life, and walking (dis)ability after
      SET. Walking distances were obtained by standardized treadmill testing according
      to the Gardner-Skinner protocol. Quality of life was measured by the 36-Item
      Short Form Health Survey, and walking (dis)ability was determined by the Walking
      Impairment Questionnaire (WIQ). Measurements were performed at baseline and after
      3, 6, 9, and 12 months. Only patients who met the 12-month follow-up measure were
      included in the analysis. RESULTS: A total of 113 men and 56 women were available
      for analysis. At baseline, groups were similar in terms of clinical
      characteristics and ACD walking distances (men, 250 meters; women, 270 meters; P
      = .45). ACD improved for both sexes. However, ACD increase was significantly
      lower for women than for men during the first 3 months of SET (Delta 280 meters
      for men vs Delta 220 meters for women; P = .04). Moreover, absolute walking
      distance was significantly shorter for women compared with men after 1 year (565
      meters vs 660 meters; P = .032). Women also reported less on several WIQ
      subdomains, although total WIQ score was similar (0.69 for men vs 0.61 for women;
      P = .592). No differences in quality of life after SET were observed.
      CONCLUSIONS: Women with IC benefit less during the first 3 months of SET and have
      lower absolute walking distances after 12 months of follow-up compared with men.
      More research is needed to determine whether gender-based IC treatment strategies
      are required.

PMID- 26304483
TI  - Surgical treatment of middle aortic syndrome due to Takayasu arteritis.

PMID- 26304484
TI  - C is for carotid injury.

PMID- 26304485
TI  - Debate: Whether an endovascular-first strategy is the optimal approach for
      treating acute mesenteric ischemia.
AB  - Acute mesenteric ischemia continues to be a life-threatening insult in often
      elderly patients with many comorbidities. Recognition and correct diagnosis can
      be an issue leading to delays in therapy that result in loss of bowel or life, or
      both. The basic surgical principals in treating acute mesenteric ischemia have
      long been early recognition, resuscitation, urgent revascularization, resection
      of necrotic bowel, and reassessment with second-look laparotomies. Endovascular
      techniques now offer a less invasive alternative, but whether an endovascular
      first or open surgery-first approach is preferred in most patients is unclear.
      Our discussants will attempt to clarify these issues. 

PMID- 26304486
TI  - Editors' commentary.

PMID- 26304487
TI  - Regarding "Options for treatment of spontaneous mesenteric artery dissection".

PMID- 26304488
TI  - The daisy chain effect in medical device approval: Progression to inferiority.

PMID- 26304489
TI  - Reply: To PMID 24655752.

PMID- 26304490
TI  - Regarding "Outcomes of persistent intraoperative type Ia endoleak after standard
      endovascular aneurysm repair".

PMID- 26304491
TI  - Reply: To PMID 25656591.

PMID- 26304492
TI  - Clinical Significance of Environmental Mycobacteria Isolated From Respiratory
      Specimens of Patients With and Without Silicosis.
AB  - OBJECTIVE: To describe the clinical, functional and radiographic differences of
      respiratory disease caused by environmental mycobacteria (EM) in patients with
      and without silicosis. METHOD: Retrospective, observational study in patients
      with nontuberculous mycobacteria isolated in the Hospital Meixoeiro (University
      Hospital of Vigo) microbiology laboratory between January 2007 and December 2013.
      Patients were grouped according to the presence or absence of silicosis and
      mycobacterial lung disease, using American Thoracic Society criteria. RESULTS: In
      156 cases, at least one species of EM had been isolated from the respiratory
      culture. A total of 71% were identified in men, 40 (25.6%) of whom had silicosis.
      Sixty patients (38.5%) met American Thoracic Society microbiological criteria:
      62.5% of the silicosis group and 30.2% of the non-silicosis group. The most
      common species were Mycobacterium avium complex, Mycobacterium genavense and
      Mycobacterium chelonae. American Thoracic Society criteria for environmental
      mycobacterial disease were met in 34 (22.7%) patients: 14 in the silicosis group
      and 20 in the non-silicosis group. Treatment was administered in 24 cases, with
      better bacteriological eradication levels in the non-silicosis group.
      CONCLUSIONS: In our series, a history of silicosis was related with a higher
      incidence of environmental mycobacterial disease. The causative species in the
      majority of cases in our setting was Mycobacterium avium complex, followed by
      Mycobacterium genavense. Patients with silicosis showed lower cure rates after
      treatment.

PMID- 26304493
TI  - A novel osmotic pump-based controlled delivery system consisting of pH-modulated
      solid dispersion for poorly soluble drug flurbiprofen: in vitro and in vivo
      evaluation.
AB  - In this study, a novel controlled release osmotic pump capsule consisting of pH
      modulated solid dispersion for poorly soluble drug flurbiprofen (FP) was
      developed to improve the solubility and oral bioavailability of FP and to
      minimize the fluctuation of plasma concentration. The pH-modulated solid
      dispersion containing FP, Kollidon(r) 12 PF and Na2CO3 at a weight ratio of
      1/4.5/0.02 was prepared using the solvent evaporation method. The osmotic pump
      capsule was assembled by semi-permeable capsule shell of cellulose acetate (CA)
      prepared by the perfusion method. Then, the solid dispersion, penetration
      enhancer, and suspending agents were tableted and filled into the capsule.
      Central composite design-response surface methodology was used to evaluate the
      influence of factors on the responses. A second-order polynomial model and a
      multiple linear model were fitted to correlation coefficient of drug release
      profile and ultimate cumulative release in 12 h, respectively. The actual
      response values were in good accordance with the predicted ones. The optimized
      formulation showed a complete drug delivery and zero-order release rate. Beagle
      dogs were used to be conducted in the pharmacokinetic study. The in vivo study
      indicated that the relative bioavailability of the novel osmotic pump system was
      133.99% compared with the commercial preparation. The novel controlled delivery
      system with combination of pH-modulated solid dispersion and osmotic pump system
      is not only a promising strategy to improve the solubility and oral
      bioavailability of poorly soluble ionizable drugs but also an effective way to
      reduce dosing frequency and minimize the plasma fluctuation. 

PMID- 26304494
TI  - Novel Histone Deacetylase Inhibitor Modulates Cardiac Peroxisome Proliferator
      Activated Receptors and Inflammatory Cytokines in Heart Failure.
AB  - BACKGROUND: Heart failure (HF) affects cardiac metabolism and inflammation.
      Histone deacetylases (HDACs) play a critical role in cardiac pathophysiology.
      This study investigated whether HDAC inhibition can regulate HF by modifying
      cardiac inflammation and peroxisome proliferator-activated receptor (PPAR)
      isoforms. METHODS: Echocardiography, electrocardiography, ELISA and Western blot
      were performed in rats with isoproterenol-induced HF, with and without orally
      administered MPT0E014 (a novel HDAC inhibitor, 50 mg/kg for 7 consecutive days).
      RESULTS: The left ventricles (LVs) of HF rats expressed significantly higher
      levels of HDAC1, HDAC2, HDAC3, HDAC4 and HDAC6 than the healthy LVs did. HF rats
      treated with MPT0E014 exhibited improved cardiac fraction shortening with
      reducing chamber size. The MPT0E014-treated HF LVs exhibited a smaller increase
      in the expression of interleukin (IL)-6, p22, SMAD2/3, extracellular signal
      regulated kinase 1/2, PPAR isoforms and circulatory tumor growth factor-beta1
      than the untreated HF LVs did. Moreover, MPT0E014-treated HF LVs expressed less
      fibroblast growth factor receptor than untreated HF LVs did. CONCLUSIONS: HDAC
      inhibition can improve cardiac function and attenuate the effects of HF on
      cardiac metabolism and inflammation, which might contribute to the beneficial
      effects of HDAC inhibition in HF.

PMID- 26304495
TI  - Differences in preferences for models of consent for biobanks between Black and
      White women.
AB  - Biobanks are essential resources, and participation by individuals from diverse
      groups is needed. Various models of consent have been proposed for secondary
      research use of biospecimens, differing in level of donor control and information
      received. Data are needed regarding participant preferences for models of
      consent, particularly among minorities. We conducted qualitative semi-structured
      interviews with 60 women to examine their attitudes about different models of
      consent. Recruitment was stratified by race (Black/White) and prior biobank
      participation (yes/no). Two coders independently coded interview transcripts.
      Qualitative thematic analysis was conducted using NVivo 10. The majority of Black
      and White participants preferred "broad" consent (i.e., blanket permission for
      secondary research use of biospecimens), and the second most preferred model for
      both groups was "study-specific" consent (i.e., consent for each future research
      study). The qualitative analysis showed that participants selected their most
      preferred model for 3 major reasons: having enough information, having control
      over their sample, and being asked for permission. Least preferred was notice
      model (i.e., participants notified that biospecimens may be used in future
      research). Attitudes toward models of consent differed somewhat by race and prior
      biobank participation. Participants preferred models of consent for secondary
      research use of biospecimens that provided them with both specific and general
      information, control over their biospecimens, and asked them to give permission
      for use. Our findings suggest that it will be important for researchers to
      provide information about future uses of biospecimens to the extent possible and
      have an explicit permission step for secondary research use. 

PMID- 26304496
TI  - Ostial atresia of left circumflex coronary artery arising from non-coronary
      sinus: a combination of rare anomalies.
AB  - Atresia of the left coronary artery ostium and right coronary artery ostium is a
      rare anatomic variant of the coronary circulation. Atresia of the left circumflex
      artery and its origin of from the non-coronary sinus have never been described.
      We report this unusual combination of rare anomalies for the first time. 

PMID- 26304497
TI  - Statistical correction of potassium in haemolysed samples.

PMID- 26304498
TI  - Statistical correction of potassium in haemolysed samples. In response to the
      letter of Adel Ismail.

PMID- 26304499
TI  - Longitudinal In Vivo Ultrasound Observations of the Surgically Repaired Zone II
      Flexor Digitorum Profundus Tendon.
AB  - The link between the healing process and functional outcomes in the surgically
      repaired digital flexor tendon is poorly understood. This clinical note describes
      those gray-scale and power Doppler (PD) ultrasound parameters that can be used to
      document longitudinal change in the morphologic and dynamic properties of the
      surgically repaired zone II flexor digitorum profundus (FDP) tendon. The method
      is supported by ultrasound data obtained from three participants at five points
      in time post-surgically (two, four, six, 12 and 18 weeks). Longitudinal
      documentation of the ultrasound properties of echogenicity, defect size, tendon
      excursion and power Doppler signal is feasible and has the potential to explore
      the possible link between changes in the structural status of surgically repaired
      flexor tendons and associated clinical outcomes. 

PMID- 26304500
TI  - Reduced Patellar Tendon Elasticity with Aging: In Vivo Assessment by Shear Wave
      Elastography.
AB  - How aging affects the elasticity of tendons has long been debated, partly because
      of the limited methods for in vivo evaluation, which differ vastly from those for
      in vitro animal studies. In this study, we tested the reliability of shear wave
      elastography (SWE) in the evaluation of patellar tendons and their change in
      elasticity with age. We recruited 62 healthy participants in three age groups: 20
      30 years (group 1), 40-50 years (group 2) and 60-70 years (group 3). Shear wave
      velocity and elastic modulus were measured at the proximal, middle and distal
      areas of the patellar tendon. Reliability was excellent at the middle area and
      fair to good at both ends. Compared with the other groups, group 3 had
      significantly decreased elastic modulus and shear wave velocity values (p <=
      0.001 vs. group 1 or 2), with significant increased side-to-side differences. SWE
      may be valuable in detecting aging tendons before visible abnormalities are
      observed on B-mode ultrasonography.

PMID- 26304501
TI  - Protein-derived acetaminophen-cysteine detection from chronic APAP is not dose
      dependent.

PMID- 26304502
TI  - Summary of European Association of Urology (EAU) Guidelines on Neuro-Urology.
AB  - CONTEXT: Most patients with neuro-urological disorders require life-long medical
      care. The European Association of Urology (EAU) regularly updates guidelines for
      the diagnosis and treatment of these patients. OBJECTIVE: To provide a summary of
      the 2015 updated EAU Guidelines on Neuro-Urology. EVIDENCE ACQUISITION:
      Structured literature searches in several databases were carried out to update
      the 2014 guidelines. Levels of evidence and grades of recommendation were
      assigned where possible. EVIDENCE SYNTHESIS: Neurological disorders often cause
      urinary tract, sexual, and bowel dysfunction. Most neuro-urological patients need
      life-long care for optimal life expectancy and quality of life. Timely diagnosis
      and treatment are essential to prevent upper and lower urinary tract
      deterioration. Clinical assessment should be comprehensive and usually includes a
      urodynamic investigation. The neuro-urological management must be tailored to the
      needs of the individual patient and may require a multidisciplinary approach.
      Sexuality and fertility issues should not be ignored. Numerous conservative and
      noninvasive possibilities of management are available and should be considered
      before a surgical approach is chosen. Neuro-urological patients require life-long
      follow-up and particular attention has to be paid to this aspect of management.
      CONCLUSIONS: The current EAU Guidelines on Neuro-Urology provide an up-to-date
      overview of the available evidence for adequate diagnosis, treatment, and follow
      up of neuro-urological patients. PATIENT SUMMARY: Patients with a neurological
      disorder often suffer from urinary tract, sexual, and bowel dysfunction and life
      long care is usually necessary. The update of the EAU Guidelines on Neuro
      Urology, summarized in this paper, enables caregivers to provide optimal support
      to neuro-urological patients. Conservative, noninvasive, or minimally invasive
      approaches are often possible.

PMID- 26304503
TI  - Contemporary Management of Stone Disease: The New EAU Urolithiasis Guidelines for
      2015.

PMID- 26304504
TI  - Health care utilization, lifestyle, and emotional factors and mammography
      practices in the Childhood Cancer Survivor Study.
AB  - BACKGROUND: Women with a history of chest radiotherapy have an increased risk of
      breast cancer; however, many do not undergo annual recommended screening
      mammography. We sought to characterize the relationship between mammography and
      potentially modifiable factors, with the goal of identifying targets for
      intervention to improve utilization. METHODS: Of 625 female participants sampled
      from the Childhood Cancer Survivor Study, who were treated with chest
      radiotherapy, 551 responded to a survey about breast cancer screening practices.
      We used multivariate Poisson regression to assess several lifestyle and emotional
      factors, health care practices, and perceived breast cancer risk, in relation to
      reporting a screening mammogram within the last two years. RESULTS: Women who had
      a Papanicolaou test [prevalence ratio (PR): 1.77; 95% confidence interval (CI)
      1.26-2.49], and who perceived their breast cancer risk as higher than the average
      woman were more likely to have had a mammogram (PR, 1.26; 95% CI, 1.09-1.46). We
      detected an attenuated effect of echocardiogram screening [PR, 0.70; 95% CI (0.52
      0.95)] on having a mammogram among older women compared with younger women.
      Smoking, obesity, physical activity, coping, and symptoms of depression and
      somatization were not associated with mammographic screening. CONCLUSION: Our
      findings suggest that compliance with routine and risk-based screening can be an
      important indicator of mammography in childhood cancer survivors. In addition,
      there is a need to ensure women understand their increased breast cancer risk, as
      a means to encouraging them to follow breast surveillance guidelines. IMPACT:
      Screening encounters could be used to promote mammography compliance in this
      population.

PMID- 26304505
TI  - Comparative study of the effects of PEGylated interferon-alpha2a versus 5
      fluorouracil on cancer stem cells in a rat model of hepatocellular carcinoma.
AB  - Cancer stem cells (CSCs) in hepatocellular carcinoma (HCC) possess tumor
      initiating, metastatic, and drug resistance properties. This study was conducted
      to evaluate the effects of PEGylated interferon-alpha2a (PEG-IFN-alpha2a) and 5
      fluorouracil (5-FU) on the expression of CSC markers and on specific pathways
      that contribute to the propagation of CSCs in HCC. HCC was initiated in rats
      using a single intraperitoneal dose of diethylnitrosamine (DENA) (200 mg/kg) and
      promoted by weekly subcutaneous injections of carbon tetrachloride (CCl4) for 6
      weeks. After the appearance of dysplastic nodules, the animals received PEG-IFN
      alpha2a or 5-FU for 8 weeks. CSC markers (OV6, CD90) and molecules related to
      transforming growth factor beta (TGF-beta) and other signaling pathways were
      assessed in hepatic tissues. The PEG-IFN-alpha2a treatment effectively suppressed
      the hepatic expression of OV6 and CD90, ameliorated the diminished hepatic
      expression of TGF-beta receptor II (TGF-betaRII) and beta2-spectrin (beta2SP),
      and significantly reduced the elevated hepatic expression of TGF-beta1,
      interleukin6 (IL6), signal transducer and activator of transcription3 (STAT3),
      and vascular endothelial growth factor (VEGF). In contrast, the 5-FU treatment
      failed to reduce the overexpression of CSC markers and barely affected the
      disrupted TGF-beta signaling. Furthermore, it had no effect on angiogenesis or
      nitrosative stress. PEG-IFN-alpha2a, but not 5-FU, could reduce the propagation
      of CSCs during the progression of HCC by upregulating the disrupted TGF-beta
      signaling, suppressing the IL6/STAT3 pathway and reducing angiogenesis. 

PMID- 26304506
TI  - Distinctive expression pattern of interleukin-17 cytokine family members in
      colorectal cancer.
AB  - Colorectal cancer (CRC) is one of the most common cancers in both genders. Even
      though interleukin (IL)-17A was shown to play an important role in intestinal
      tumourigenesis and CRC, other IL-17 family members were not studied well. We
      therefore studied the expression of IL-17 cytokine family members in CRC. Ten
      healthy colons and ten CRC mucosa were immunostained for IL-17B, IL-17C, IL-17E,
      and IL-17F, and their receptors IL-17RA, IL-17RB, and IL-17RC. Double
      immunofluorescence staining of the CRC mucosa was done for IL-17B with markers of
      neutrophils, endothelial cells, macrophages, T cells, mast cells, or fibroblasts.
      While IL-17B was increased in CRC with a strong presence both in the epithelial
      and stromal compartments, IL-17C showed different expression depending on the
      grade of differentiation and IL-17E remained unchanged. In contrast, IL-17F was
      decreased in CRC compared to healthy control. Colon epithelial cells stained
      positive for IL-17RA, IL-17RB, and IL-17RC in both healthy control and CRC.
      Neutrophils were the main source of IL-17B in the stroma. IL-17 family members
      demonstrated distinct expression patterns in CRC, suggesting a differential role
      exerted by each member in colon carcinogenesis. 

PMID- 26304507
TI  - Association of gastrointestinal gland cancer susceptibility loci with esophageal
      carcinoma among the Chinese Han population: a case-control study.
AB  - Esophageal carcinoma (EC) is a common malignancy worldwide. Previous studies
      indicated that gastrointestinal gland cancer and EC share some susceptibility
      loci. Our aim was to identify new single nucleotide polymorphisms (SNPs)
      associated with EC by investigating whether known gastrointestinal cancers
      susceptibility loci are found in EC patients. A Chinese Han population case
      control study was conducted to assess SNP associations with EC risk. Twenty-six
      SNPs were selected from gastrointestinal cancer susceptibility loci, and 360 EC
      patients and 310 controls were genotyped for these SNPs using Sequenom MassARRAY
      technology. The association of SNP frequencies with EC was analyzed by chi-square
      tests, and genetic model analysis. After Hardy-Weinberg equilibrium (HWE) p value
      screening, we excluded two SNPs. Based on chi-square tests, the minor alleles of
      rs13294589 (p = 0.046) and rs4924935 (p = 0.046) were correlated with reduced EC
      risk and rs4269383 (p = 0.010) and rs10953615 (p = 0.036) were correlated with
      increased EC risk. In the genetic model analyses, we found that the minor alleles
      "T" of rs401681, "A" of rs10088262, and "C" of rs4924935 may reduce the risk of
      EC. rs401681 has previously been reported to be associated with EC. To the best
      of our knowledge, we are the first to report an association of the other five
      SNPs with EC. Our findings provide evidence for the genetic variants associated
      with susceptibility to EC in the Chinese Han population, which might be used as
      potential molecular markers for detecting susceptibility to EC in Chinese Han
      people. 

PMID- 26304508
TI  - Response Times to Gustatory-Olfactory Flavor Mixtures: Role of Congruence.
AB  - A mixture of perceptually congruent gustatory and olfactory flavorants (sucrose
      and citral) was previously shown to be detected faster than predicted by a model
      of probability summation that assumes stochastically independent processing of
      the individual gustatory and olfactory signals. This outcome suggests substantial
      integration of the signals. Does substantial integration also characterize
      responses to mixtures of incongruent flavorants? Here, we report simple response
      times (RTs) to detect brief pulses of 3 possible flavorants: monosodium
      glutamate, MSG (gustatory: "umami" quality), citral (olfactory: citrus quality),
      and a mixture of MSG and citral (gustatory-olfactory). Each stimulus (and, on a
      fraction of trials, water) was presented orally through a computer-operated,
      automated flow system, and subjects were instructed to press a button as soon as
      they detected any of the 3 non-water stimuli. Unlike responses previously found
      to the congruent mixture of sucrose and citral, responses here to the incongruent
      mixture of MSG and citral took significantly longer (RTs were greater) and showed
      lower detection rates than the values predicted by probability summation. This
      outcome suggests that the integration of gustatory and olfactory flavor signals
      is less extensive when the component flavors are perceptually incongruent rather
      than congruent, perhaps because incongruent flavors are less familiar. 

PMID- 26304509
TI  - Feedstuff and poor latrines may put pigs at risk of cysticercosis--A case-control
      study.
AB  - Attempts to control Taenia solium in low-income countries have been unsuccessful
      or unsustainable. This could indicate a 'missing link' in our understanding of
      the transmission dynamics of the parasite and possibly the magnitude of
      environmental contamination. We aimed to identify risk factors associated with
      porcine cysticercosis using a case-control study design, utilising known
      information on persistent or multiple infections of porcine cysticercosis. The
      study, a combination of questionnaire interviews and observational surveys, was
      conducted in July 2014 in the two districts Mbeya and Mbozi, Tanzania. Study
      households were identified based on their status regarding porcine cysticercosis
      prevalence and allocated into cases or controls based on previous porcine
      cysticercosis presence. This resulted in 43 farmers in the case group and 50
      farmers in the control group, from 20 villages. Potato peels were said to be
      given to pigs either raw or boiled by 46% of the farmers. Based on logistic
      regression porcine cysticercosis could be associated with absence or a completely
      open latrine (p=0.035, OR 5.98, CI: 1.33-43.02) compared to an enclosed latrine.
      Feeding potato peels to pigs was also associated with increased risk of infection
      (p=0.007, OR 3.45, CI: 1.43-8.79). Logistic analysis including the pig management
      system indicated pigs kept in elevated pens (p=0.049, OR 5.33, CI: 1.08-32.27)
      and on a dirt floor (p=0.041, OR 9.87, CI: 1.29-114.55) were more likely to be
      infected compared to a cemented floor. Whether potato peels are contaminated with
      Taenia eggs before they reach the household or whether the contamination is from
      water or dirty hands during the process of peeling, remains to be confirmed. This
      study suggests that detailed assessment of a number of areas of pig management is
      essential for designing effective control programmes. 

PMID- 26304510
TI  - Projected Increase in Periprosthetic Joint Infections Secondary to Rise in
      Diabetes and Obesity.
AB  - Total joint arthroplasties (TJAs) are projected to increase, along with increased
      complications like periprosthetic joint infections (PJIs). However, no study has
      projected TJAs secondary to PJI and how these relate to comorbidities in these
      patients. The NIS database was assessed from 1993 to 2000 to evaluate primary and
      revision TJAs, and projections were made until 2028. ICD-9 codes were used to
      identify patients with obesity, diabetes, and PJI. Rates of diabetes and adult
      obesity are predicted to increase for both genders, and patients receiving
      revision surgery for PJI are predicted to increase over time; males had higher
      rates than females. With an exponential increase of PJI secondary to diabetes and
      obesity, it is imperative that orthopedists intervene in these patients prior to
      TJA to decrease PJI's burden. 

PMID- 26304512
TI  - Ubiquitous Detection of Artificial Sweeteners and Iodinated X-ray Contrast Media
      in Aquatic Environmental and Wastewater Treatment Plant Samples from Vietnam, The
      Philippines, and Myanmar.
AB  - Water samples from Vietnam, The Philippines, and Myanmar were analyzed for
      artificial sweeteners (ASs) and iodinated X-ray contrast media (ICMs). High
      concentrations (low micrograms per liter) of ASs, including aspartame, saccharin,
      and sucralose, were found in wastewater treatment plant (WWTP) influents from
      Vietnam. Three ICMs, iohexol, iopamidol, and iopromide were detected in
      Vietnamese WWTP influents and effluents, suggesting that these ICMs are
      frequently used in Vietnam. ASs and ICMs were found in river water from downtown
      Hanoi at concentrations comparable to or lower than the concentrations in WWTP
      influents. The ASs and ICMs concentrations in WWTP influents and adjacent surface
      water significantly correlated (r (2) = 0.99, p < 0.001), suggesting that
      household wastewater is discharged directly into rivers in Vietnam. Acesulfame
      was frequently detected in northern Vietnamese groundwater, but the
      concentrations varied spatially by one order of magnitude even though the
      sampling points were very close together. This implies that poorly performing
      domestic septic tanks sporadically leak household wastewater into groundwater.
      High acesulfame, cyclamate, saccharin, and sucralose concentrations were found in
      surface water from Manila, The Philippines. The sucralose concentrations were one
      order of magnitude higher in the Manila samples than in the Vietnamese samples,
      indicating that more sucralose is used in The Philippines than in Vietnam.
      Acesulfame and cyclamate were found in surface water from Pathein (rural) and
      Yangon (urban) in Myanmar, but no ICMs were found in the samples. The ASs
      concentrations were two-three orders of magnitude lower in the samples from
      Myanmar than in the samples from Vietnam and The Philippines, suggesting that
      different amounts of ASs are used in these countries. We believe this is the
      first report of persistent ASs and ICMs having ubiquitous distributions in
      economically emerging South Asian countries. 

PMID- 26304513
TI  - Mechanistic similarities between trauma, atherosclerosis, and other inflammatory
      processes.
AB  - Most human diseases, including trauma, atherosclerosis, and malignancy, can be
      characterized by either an overexuberant inflammatory response or an inadequate
      immunologic response. As our understanding of the mechanisms underlying these
      inflammatory aberrations improves, so should our approach to the patient. The
      development of novel technologies capable of exploiting inflammatory mediators
      will undoubtedly play a role in future patient-directed therapies. Trauma
      surgeons are uniquely positioned to usher in a new era of patient diagnostics and
      patient-directed therapies based on an understanding of the immune system's
      response to stimuli. These improvements are likely to affect not only trauma care
      but all aspects of medicine. 

PMID- 26304511
TI  - Molecular Mapping of Sinoatrial Node HCN Channel Expression in the Human Heart.
AB  - BACKGROUND: The hyperpolarization-activated current, If, plays an important role
      in sinoatrial node (SAN) pacemaking. Surprisingly, the distribution of
      hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in human SAN
      has only been investigated at the mRNA level. Our aim was to define the
      expression pattern of HCN proteins in human SAN and different atrial regions.
      METHODS AND RESULTS: Entire SAN complexes were isolated from failing (n=5) and
      nonfailing (n=9) human hearts cardioplegically arrested in the operating room.
      Three-dimensional intramural SAN structure was identified as the fibrotic compact
      region around the SAN artery with Connexin 43-negative pacemaker cardiomyocytes
      visualized in Masson's trichrome and immunostained cryosections. SAN protein was
      precisely isolated from the adjacent frozen SAN tissue blocks using a 16G biopsy
      needle. The purity of the SAN protein was confirmed by Connexin 43 immunoblot.
      All 3 HCN isoform proteins were detected in SAN. HCN1 was predominantly
      distributed in the human SAN with a 125.1+/-40.2 (n=12) expression ratio of SAN
      to right atrium. HCN2 and HCN4 expression levels were higher in SAN than in
      atria, with SAN to right atrium ratios of 6.1+/-0.9 and 4.6+/-0.6 (n=12),
      respectively. CONCLUSIONS: This is the first study to conduct precise 3D
      molecular mapping of the human SAN by isolating pure pacemaker SAN tissue. All 3
      cardiac HCN isoforms had higher expression in the SAN than in the atria. HCN1 was
      almost exclusively expressed in SAN, emphasizing its utility as a new specific
      molecular marker of the human SAN and as a potential target of specific
      treatments intended to modify sinus rhythm.

PMID- 26304514
TI  - Does difficulty functioning in the surrogate role equate to vulnerability in
      critical illness research? Use of path analysis to examine the relationship
      between difficulty providing substituted judgment and receptivity to critical
      illness research participation.
AB  - PURPOSE: Individuals who struggle to provide substitute judgment for the
      critically ill often find it challenging to engage in decision making for
      therapeutic interventions. Although essential to the conduct of research, how
      these individuals respond to requests for clinical trial participation is poorly
      understood. METHODS: Survey data collected to examine surrogate attitudes toward
      research provided the conceptual framework to explore influences on decision
      making. Path analysis was used to derive the final model (nonlatent, fully
      recursive, 1 indicator/variable). RESULTS: Surrogates with list-wise complete
      records (406) were analyzed. The following variables were not retained in the
      final model: education, income, religiosity, decision-making experience,
      discussion of patient's wishes, number of individuals assisting with decision
      making, trust in care providers, difficulty making decisions, and responsibility
      for decision making. Being white and having experience making treatment decisions
      for the patient during the current intensive care unit encounter affected the
      likelihood the surrogate would permit participation in research positively
      (parameter estimates, 0.281 and 0.06, respectively). No variable reflecting
      difficulty functioning in the surrogate role was associated with permitting
      research participation. CONCLUSIONS: We were unable to demonstrate a relationship
      between perceived difficulty in decision making in the surrogate role and
      receptivity to clinical trial participation.

PMID- 26304515
TI  - Electrophysiology testing and catheter ablation are helpful when evaluating
      asymptomatic patients with Wolff-Parkinson-White pattern: the pro perspective.
AB  - Important advances in the natural history and diagnosis of, and therapy for,
      asymptomatic Wolff-Parkinson-White (WPW) syndrome have been made in the last
      decade by our group. These data have necessitated revisiting current practice
      guidelines to decide on the optimal management of the asymptomatic WPW
      population. There has also been an emphasis on identifying initially asymptomatic
      individuals who are at risk by nationwide screening programs using the
      electrocardiogram for prophylactic catheter ablation to prevent the lifetime risk
      of sudden cardiac death, particularly in young asymptomatic people, because only
      a subgroup of them is at high risk, requiring early catheter ablation. 

PMID- 26304516
TI  - Electrophysiology testing and catheter ablation are helpful when evaluating
      asymptomatic patients with Wolff-Parkinson-White pattern: the con perspective.
AB  - The association between asymptomatic Wolff-Parkinson-White (WPW) syndrome and
      sudden cardiac death (SCD) has been well documented. The inherent properties of
      the accessory pathway determine the risk of SCD in WPW, and catheter ablation
      essentially eliminates this risk. An approach to WPW syndrome is needed that
      incorporates the patient's individualized considerations into the decision
      making. Patients must understand that there is a trade-off of a small immediate
      risk of an invasive approach for elimination of a small lifetime risk of the
      natural history of asymptomatic WPW. Clinicians can minimize the invasive risk by
      only performing ablation for patients with at-risk pathways. 

PMID- 26304517
TI  - Catheter ablation of atrial fibrillation should be offered as primary therapy:
      what's your hurry?
AB  - The appropriate initial treatment of a middle-aged individual with symptomatic
      paroxysms of atrial fibrillation, diabetes, and hypertension should focus on
      eliminating the underlying causes of disease to safely reduce morbidity and
      prolong life. An initial strategy using ablation temporarily reduces arrhythmia
      symptoms and exposes the individual to potentially needless risk and repeat
      procedures. Randomized trials have not established the superiority of ablation to
      antiarrhythmic drugs with respect to prolonging life or reducing serious
      morbidity. It is appropriate to treat modestly symptomatic individuals with
      antiarrhythmic drugs while performing aggressive risk factor modification. 

PMID- 26304518
TI  - Patients with minimal atrial fibrillation events should not undergo concomitant
      atrial ablation during open heart procedures.
AB  - Several randomized controlled trials and meta-analyses have demonstrated improved
      freedom from atrial fibrillation with intraoperative atrial ablation. However,
      the increased bypass time and the risk for ablation-related complications should
      be weighed against the benefits in the decision-making. It is important to
      establish reasonable criteria to define candidates for surgical ablation.
      Furthermore, the efficacy and short- and long-term risks related to surgical
      ablation need to be considered. This article reviews the data on surgical
      ablation of atrial fibrillation as it pertains to these important issues. As
      shown the evidence does not support surgical ablation at the time of coronary
      artery bypass graft in some patients. 

PMID- 26304520
TI  - Left atrial appendage closure device in atrial fibrillation.
AB  - The relationship of stroke and atrial fibrillation seems to become more complex
      as we gain more knowledge of the issue. Recent studies have questioned the
      temporal relationship between the two, which also questions causation. Left
      atrial appendage closure is an attractive, but unproven technology when compared
      with the 50-year experience with warfarin. In a patient who is on warfarin and
      having no issues with bleeding, medication intolerance, or lack of efficacy, it
      is difficult to justify stopping the drug and placing a closure device as sole
      therapy to prevent a stroke. 

PMID- 26304519
TI  - Left atrial appendage closure is preferred to chronic warfarin therapy: the pro
      perspective.
AB  - Atrial fibrillation (AF) is associated with increased rates of death, stroke,
      heart failure, hospitalization, degraded quality of life, reduced exercise
      capacity, and left ventricular dysfunction. An oral anticoagulant reduces the
      risk of stroke; however, it places the patient at risk for bleeding
      complications. Weighing the stroke and bleeding risks remains the key for optimal
      treatment. Cardiac interventions that can obviate long-term oral anticoagulation
      hold great promise for the future care of patients with AF and high stroke risk.
      The percutaneously deployable Watchman device is a paradigm shift in how
      clinicians can abate the need for continued oral anticoagulation. 

PMID- 26304521
TI  - To extract or retain a sterile, nonfunctional lead: the case for extraction.
AB  - Decision-making regarding extracting or abandoning sterile but nonfunctioning ICD
      leads has to be individualized. Providing recommendations to patients and their
      families requires a careful weighing of pros and cons and understanding of the
      availability of local expertise. Decision models to help with these clinical
      scenarios have started to become available but remain in their infancy. 

PMID- 26304522
TI  - Extraction of sterile leads is the preferred approach rather than implanting a
      new lead: the con perspective.
AB  - Lead malfunction is a common problem in implantable cardiac device patients and
      is expected to increase with the aging of leads. There is a weak indication for
      extraction of superfluous leads with the potential for cardiac implantable
      electronic device interference and abandoned or redundant leads; much remains to
      be learned from clinical practice. Lead extraction, although safe in experienced
      hands, remains a high-risk procedure, especially in lower-volume centers and/or
      when performed by lower-volume operators. Therefore, a strategy of abandoning
      nonfunctioning leads is reasonable, and lead extractions should be reserved for
      cases with system infection or high lead burden. 

PMID- 26304523
TI  - Cardiac resynchronization therapy is appropriate for all patients requiring
      chronic right ventricular pacing: the pro perspective.
AB  - Long-term right ventricular pacing has deleterious effects on the left ventricle
      (LV). The risk of pacemaker-induced cardiomyopathy (PICM) seems to be lower in
      patients with a normal LV ejection fraction (LVEF). Patients developing PICM
      respond favorably to a cardiac resynchronization therapy upgrade, suggesting that
      the dysfunction is partially reversible. Biventricular pacing has emerged as a
      treatment and/or prevention of PICM. Cumulative pacing greater than 40% of the
      time is considered the most important risk factor for PICM. No organizational
      guidelines exist for preventive biventricular pacing. The decision to pursue
      biventricular pacing should be individualized. 

PMID- 26304524
TI  - Cardiac resynchronization therapy is appropriate for all patients requiring
      chronic right ventricular pacing: the con perspective.
AB  - There has been compelling evidence for the use of biventricular (BiV) pacing to
      reduce mortality and heart failure (HF) hospitalization in patients with HF
      symptoms, depressed ejection fraction (EF), and a broad QRS. Cardiac
      resynchronization therapy (CRT) provides benefit for patients with depressed EF
      and minimal HF symptoms. Although data from CRT trials are compelling, clinical
      evidence to recommend BiV pacing to all patients who require a high degree of
      right ventricular (RV) pacing are lacking. This article summarizes the relevant
      studies demonstrating that BiV pacing is not appropriate therapy for all patients
      who require chronic RV pacing. 

PMID- 26304525
TI  - Biventricular pacemaker/defibrillators versus biventricular pacemakers in
      patients with non-ischemic cardiomyopathy.
AB  - The decision to employ defibrillator therapy in patients with non-ischemic
      cardiomyopathy is driven by reduction in mortality. The strength of data
      supporting this therapy has led to its incorporation in medical guidelines and
      general practice across the world. Cardiac resynchronization therapy has also
      been proven to reduce heart failure hospitalization and improve quality of life.
      Although trends toward reduction in arrhythmic events have been observed, results
      in multicenter, randomized controlled trials have not been compelling for stand
      alone use in most patients who currently meet criteria for defibrillator therapy.

PMID- 26304526
TI  - Patients with nonischemic cardiomyopathy requiring cardiac resynchronization
      therapy should also undergo implantation of a primary prevention defibrillator:
      the con perspective.
AB  - This article describes a 45-year-old lady with longstanding dilated
      cardiomyopathy, who has progressed to New York Heart Association class III and
      has failed to respond to optimal pharmacologic therapy. On the basis of gender
      and the presence of an left bundle branch block, she has good prospects of
      responding to cardiac resynchronization therapy. In the background of nonischemic
      cardiomyopathy and the absence of myocardial scarring on cardiovascular magnetic
      resonance, her annualized risk of sudden cardiac death is low, estimated at 2.6%.

PMID- 26304527
TI  - Device therapy for acute systolic heart failure and atrial fibrillation.
AB  - Patients with newly diagnosed cardiomyopathy require careful assessment of cause
      and initiation of treatment before the decision is made to implant an internal
      cardiac defibrillator. In patients with medicine-refractory atrial fibrillation
      and cardiomyopathy, atrioventricular node ablation and implantation of a
      biventricular pacemaker is the therapy of choice when tachycardia-induced
      cardiomyopathy is suspected and curative therapy is not possible. 

PMID- 26304528
TI  - Device therapy in the setting of long QT syndrome.
AB  - Congenital long QT syndrome (LQTS) is an inherited disorder of myocardial
      repolarization characterized by prolongation of the QT interval associated with
      life-threatening polymorphic ventricular tachycardia. The treatment of congenital
      LQTS involves antiadrenergic therapies: beta-blockers and surgical left cardiac
      sympathetic denervation (LCSD) to decrease sympathetic input to the heart,
      cardiac pacing, and implantable cardioverter-defibrillator (ICDs). Although this
      article focuses on the role of device therapy for the treatment of LQTS, it also
      discusses the role of beta-blockers and LCSD because they are concomitant with
      device therapy. After implantation, programming should be optimized to minimize
      the risk for inappropriate ICD therapies. 

PMID- 26304529
TI  - Generator exchange in a primary prevention cardiac resynchronziation responder:
      do you reimplant a defibrillator?
AB  - This case-based review discusses the benefits of cardiac resynchronization
      therapy (CRT) and whether defibrillation function is necessary in CRT responders.
      An evaluation of the literature and evidence to date is discussed.
      Recommendations based on these data, expert opinion, and recently published
      appropriate use criteria are given. 

PMID- 26304530
TI  - Management of pace-terminated ventricular arrhythmias.
AB  - An implantable-cardioverter defibrillator (ICD) can terminate ventricular
      arrhythmias by delivering a shock or by antitachycardia pacing (ATP). The ATP
      works by capturing the excitable gap and disrupting re-entrant ventricular
      arrhythmias. Multiple studies have demonstrated that ATP is successful at
      terminating ventricular tachycardia (VT). Shocks from the ICD are associated with
      higher mortality. The data are conflicting about whether appropriate ATP is
      associated with higher mortality. In a patient with VT that is treated by ATP,
      the patient's guideline-based heart failure medications should be maximized. The
      use of VT ablation after appropriate and successful ATP requires additional
      studies. 

PMID- 26304531
TI  - Management of device-detected atrial high-rate episodes.
AB  - Atrial tachyarrhythmias are common in patients with cardiac implantable
      electronic devices (CIEDs) with atrial leads. These atrial tachyarrhythmias are
      detected as atrial high-rate episodes (AHREs) by the CIED. AHREs may be brief,
      infrequent, and asymptomatic, and may be detected before clinical arrhythmia is
      apparent. These subclinical device-detected AHREs are associated with an
      increased stroke risk, similar to, but to a lesser degree than, clinically
      apparent atrial fibrillation detected by routine methods. Whether a specific
      duration of AHREs is needed before the risk of stroke increases and whether
      treatment with anticoagulation for subclinical device-detected AHREs reduces
      stroke risk is unclear. 

PMID- 26304532
TI  - Approach to ablation of unmappable ventricular arrhythmias.
AB  - Most patients with structural heart disease referred for ventricular tachycardia
      ablation have unstable tachycardias not suitable for conventional mapping (ie,
      entrainment mapping). Substrate-guided mapping and ablation during sinus rhythm
      are intended to overcome the limitations of conventional mapping and ablation.
      Substrate ablation permits elimination of multiple ventricular tachycardias
      irrespective of their inducibility during the procedure or their hemodynamic
      tolerability. Moreover, the elimination/isolation of the arrhythmogenic substrate
      identified during sinus rhythm has been associated with better outcomes. There is
      currently no standardized approach for substrate-guided ablation. This article
      discusses the main aspects of the proposed techniques and substrate ablation
      targets. 

PMID- 26304533
TI  - The role of defibrillation testing.
AB  - The induction and termination of ventricular fibrillation at the time of
      defibrillator insertion (defibrillation testing [DT]) has traditionally been an
      integral component of implantable cardioverter-defibrillator (ICD) implantation.
      However, over the last 10 years, published series suggested a high rate of first
      shock efficacy for clinical ventricular arrhythmias, even if no DT was done. Over
      the same time, several published reports and series have shown uncommon but
      serious complications related to DT. Throughout the world, there has been a
      steady decline in the proportion of patients receiving an ICD who undergo DT,
      which, in many regions, is less than 50%. 

PMID- 26304534
TI  - Ethical considerations for turning off pacemakers and defibrillators.
AB  - The 2010 guidelines regarding management of cardiovascular implantable electronic
      devices (CIEDs) conclude that patient requests to deactivate these devices at the
      end of life should be honored. Nevertheless, many clinicians and patients report
      feeling uncomfortable discontinuing such therapies, particularly pacemakers. If
      the principles of clinical ethics are followed, turning off CIEDs at the end of
      life is morally permissible. Clinicians managing CIEDs should discuss the option
      of deactivation with the patient at the time of implantation and be prepared to
      reopen the question as warranted by the patient's clinical course and respect for
      the patient's authentic values. 

PMID- 26304535
TI  - Controversies in electrophysiology.

PMID- 26304536
TI  - The value of a healthy debate.

PMID- 26304537
TI  - The mRNA related ceRNA-ceRNA landscape and significance across 20 major cancer
      types.
AB  - Cross-talk between competitive endogenous RNAs (ceRNAs) through shared miRNAs
      represents a novel layer of gene regulation that plays important roles in the
      physiology and development of cancers. However, a global view of their system
      level properties across various types of cancers is still unknown. Here, we
      constructed the mRNA related ceRNA-ceRNA interaction landscape across 20 cancer
      types by systematically analyzing molecular profiles of 5203 tumors and miRNA
      regulations. Our study highlights the conserved features shared by pan-cancer and
      higher similarity within similar origin cell type. Moreover, a core ceRNA network
      was identified. Function analysis identified a common theme of cancer hallmarks,
      however they exhibit phenotype-specific connectivity patterns. Besides, we found
      a marked rewiring in the ceRNA program between various cancers, and further
      revealed conserved and rewired network ceRNA hubs in each cancer, which were
      tensely competitive interactions to constitute conserved and cancer-specific
      modules. By providing mechanistic linkage between known cancer miRNAs, their
      mediated ceRNA-ceRNA interactions, and the associations with known cancer
      hallmarks, the inferred cancer ceRNA-ceRNA interaction landscape will serve as a
      powerful public resource for further biological discoveries of tumorigenesis. 

PMID- 26304539
TI  - DNA-binding protein prediction using plant specific support vector machines:
      validation and application of a new genome annotation tool.
AB  - There are currently 151 plants with draft genomes available but levels of
      functional annotation for putative protein products are low. Therefore, accurate
      computational predictions are essential to annotate genomes in the first
      instance, and to provide focus for the more costly and time consuming functional
      assays that follow. DNA-binding proteins are an important class of proteins that
      require annotation, but current computational methods are not applicable for
      genome wide predictions in plant species. Here, we explore the use of species and
      lineage specific models for the prediction of DNA-binding proteins in plants. We
      show that a species specific support vector machine model based on Arabidopsis
      sequence data is more accurate (accuracy 81%) than a generic model (74%), and
      based on this we develop a plant specific model for predicting DNA-binding
      proteins. We apply this model to the tomato proteome and demonstrate its ability
      to perform accurate high-throughput prediction of DNA-binding proteins. In doing
      so, we have annotated 36 currently uncharacterised proteins by assigning a
      putative DNA-binding function. Our model is publically available and we propose
      it be used in combination with existing tools to help increase annotation levels
      of DNA-binding proteins encoded in plant genomes. 

PMID- 26304538
TI  - Discovery of an essential nucleotidylating activity associated with a newly
      delineated conserved domain in the RNA polymerase-containing protein of all
      nidoviruses.
AB  - RNA viruses encode an RNA-dependent RNA polymerase (RdRp) that catalyzes the
      synthesis of their RNA(s). In the case of positive-stranded RNA viruses belonging
      to the order Nidovirales, the RdRp resides in a replicase subunit that is
      unusually large. Bioinformatics analysis of this non-structural protein has now
      revealed a nidoviral signature domain (genetic marker) that is N-terminally
      adjacent to the RdRp and has no apparent homologs elsewhere. Based on its
      conservation profile, this domain is proposed to have nucleotidylation activity.
      We used recombinant non-structural protein 9 of the arterivirus equine arteritis
      virus (EAV) and different biochemical assays, including irreversible labeling
      with a GTP analog followed by a proteomics analysis, to demonstrate the manganese
      dependent covalent binding of guanosine and uridine phosphates to a
      lysine/histidine residue. Most likely this was the invariant lysine of the newly
      identified domain, named nidovirus RdRp-associated nucleotidyltransferase
      (NiRAN), whose substitution with alanine severely diminished the described
      binding. Furthermore, this mutation crippled EAV and prevented the replication of
      severe acute respiratory syndrome coronavirus (SARS-CoV) in cell culture,
      indicating that NiRAN is essential for nidoviruses. Potential functions supported
      by NiRAN may include nucleic acid ligation, mRNA capping and protein-primed RNA
      synthesis, possibilities that remain to be explored in future studies. 

PMID- 26304540
TI  - Histone variant H3.3 provides the heterochromatic H3 lysine 9 tri-methylation
      mark at telomeres.
AB  - In addition to being a hallmark at active genes, histone variant H3.3 is
      deposited by ATRX at repressive chromatin regions, including the telomeres. It is
      unclear how H3.3 promotes heterochromatin assembly. We show that H3.3 is targeted
      for K9 trimethylation to establish a heterochromatic state enriched in
      trimethylated H3.3K9 at telomeres. In H3f3a(-/-) and H3f3b(-/-) mouse embryonic
      stem cells (ESCs), H3.3 deficiency results in reduced levels of H3K9me3, H4K20me3
      and ATRX at telomeres. The H3f3b(-/-) cells show increased levels of telomeric
      damage and sister chromatid exchange (t-SCE) activity when telomeres are
      compromised by treatment with a G-quadruplex (G4) DNA binding ligand or by ASF1
      depletion. Overexpression of wild-type H3.3 (but not a H3.3K9 mutant) in H3f3b(-/
      ) cells increases H3K9 trimethylation level at telomeres and represses t-SCE
      activity induced by a G4 ligand. This study demonstrates the importance of H3.3K9
      trimethylation in heterochromatin formation at telomeres. It provides insights
      into H3.3 function in maintaining integrity of mammalian constitutive
      heterochromatin, adding to its role in mediating transcription memory in the
      genome. 

PMID- 26304541
TI  - The energetic basis of the DNA double helix: a combined microcalorimetric
      approach.
AB  - Microcalorimetric studies of DNA duplexes and their component single strands
      showed that association enthalpies of unfolded complementary strands into
      completely folded duplexes increase linearly with temperature and do not depend
      on salt concentration, i.e. duplex formation results in a constant heat capacity
      decrement, identical for CG and AT pairs. Although duplex thermostability
      increases with CG content, the enthalpic and entropic contributions of an AT pair
      to duplex formation exceed that of a CG pair when compared at the same
      temperature. The reduced contribution of AT pairs to duplex stabilization comes
      not from their lower enthalpy, as previously supposed, but from their larger
      entropy contribution. This larger enthalpy and particularly the greater entropy
      results from water fixed by the AT pair in the minor groove. As the increased
      entropy of an AT pair exceeds that of melting ice, the water molecule fixed by
      this pair must affect those of its neighbors. Water in the minor groove is, thus,
      orchestrated by the arrangement of AT groups, i.e. is context dependent. In
      contrast, water hydrating exposed nonpolar surfaces of bases is responsible for
      the heat capacity increment on dissociation and, therefore, for the temperature
      dependence of all thermodynamic characteristics of the double helix. 

PMID- 26304542
TI  - Competitive interaction of monovalent cations with DNA from 3D-RISM.
AB  - The composition of the ion atmosphere surrounding nucleic acids affects their
      folding, condensation and binding to other molecules. It is thus of fundamental
      importance to gain predictive insight into the formation of the ion atmosphere
      and thermodynamic consequences when varying ionic conditions. An early step
      toward this goal is to benchmark computational models against quantitative
      experimental measurements. Herein, we test the ability of the three dimensional
      reference interaction site model (3D-RISM) to reproduce preferential interaction
      parameters determined from ion counting (IC) experiments for mixed alkali
      chlorides and dsDNA. Calculations agree well with experiment with slight
      deviations for salt concentrations >200 mM and capture the observed trend where
      the extent of cation accumulation around the DNA varies inversely with its ionic
      size. Ion distributions indicate that the smaller, more competitive cations
      accumulate to a greater extent near the phosphoryl groups, penetrating deeper
      into the grooves. In accord with experiment, calculated IC profiles do not vary
      with sequence, although the predicted ion distributions in the grooves are
      sequence and ion size dependent. Calculations on other nucleic acid conformations
      predict that the variation in linear charge density has a minor effect on the
      extent of cation competition. 

PMID- 26304543
TI  - Cis-acting signals modulate the efficiency of programmed DNA elimination in
      Paramecium tetraurelia.
AB  - In Paramecium, the regeneration of a functional somatic genome at each sexual
      event relies on the elimination of thousands of germline DNA sequences, known as
      Internal Eliminated Sequences (IESs), from the zygotic nuclear DNA. Here, we
      provide evidence that IESs' length and sub-terminal bases jointly modulate IES
      excision by affecting DNA conformation in P. tetraurelia. Our study reveals an
      excess of complementary base pairing between IESs' sub-terminal and contiguous
      sites, suggesting that IESs may form DNA loops prior to cleavage. The degree of
      complementary base pairing between IESs' sub-terminal sites (termed Cin-score) is
      positively associated with IES length and is shaped by natural selection.
      Moreover, it escalates abruptly when IES length exceeds 45 nucleotides (nt),
      indicating that only sufficiently large IESs may form loops. Finally, we find
      that IESs smaller than 46 nt are favored targets of the cellular surveillance
      systems, presumably because of their relatively inefficient excision. Our
      findings extend the repertoire of cis-acting determinants for IES
      recognition/excision and provide unprecedented insights into the distinct
      selective pressures that operate on IESs and somatic DNA regions. This
      information potentially moves current models of IES evolution and of mechanisms
      of IES recognition/excision forward. 

PMID- 26304544
TI  - Cooperation meets competition in microRNA-mediated DMPK transcript regulation.
AB  - The fundamental role of microRNAs (miRNAs) in the regulation of gene expression
      has been well-established, but many miRNA-driven regulatory mechanisms remain
      elusive. In the present study, we demonstrate that miRNAs regulate the expression
      of DMPK, the gene mutated in myotonic dystrophy type 1 (DM1), and we provide
      insight regarding the concerted effect of the miRNAs on the DMPK target.
      Specifically, we examined the binding of several miRNAs to the DMPK 3' UTR using
      luciferase assays. We validated the interactions between the DMPK transcript and
      the conserved miR-206 and miR-148a. We suggest a possible cooperativity between
      these two miRNAs and discuss gene targeting by miRNA pairs that vary in distance
      between their binding sites and expression profiles. In the same luciferase
      reporter system, we showed miR-15b/16 binding to the non-conserved CUG repeat
      tract present in the DMPK transcript and that the CUG-repeat-binding miRNAs might
      also act cooperatively. Moreover, we detected miR-16 in cytoplasmic foci formed
      by exogenously expressed RNAs with expanded CUG repeats. Therefore, we propose
      that the expanded CUGs may serve as a target for concerted regulation by miRNAs
      and may also act as molecular sponges for natural miRNAs with CAG repeats in
      their seed regions, thereby affecting their physiological functions. 

PMID- 26304545
TI  - LARVA: an integrative framework for large-scale analysis of recurrent variants in
      noncoding annotations.
AB  - In cancer research, background models for mutation rates have been extensively
      calibrated in coding regions, leading to the identification of many driver genes,
      recurrently mutated more than expected. Noncoding regions are also associated
      with disease; however, background models for them have not been investigated in
      as much detail. This is partially due to limited noncoding functional annotation.
      Also, great mutation heterogeneity and potential correlations between neighboring
      sites give rise to substantial overdispersion in mutation count, resulting in
      problematic background rate estimation. Here, we address these issues with a new
      computational framework called LARVA. It integrates variants with a comprehensive
      set of noncoding functional elements, modeling the mutation counts of the
      elements with a beta-binomial distribution to handle overdispersion. LARVA,
      moreover, uses regional genomic features such as replication timing to better
      estimate local mutation rates and mutational hotspots. We demonstrate LARVA's
      effectiveness on 760 whole-genome tumor sequences, showing that it identifies
      well-known noncoding drivers, such as mutations in the TERT promoter.
      Furthermore, LARVA highlights several novel highly mutated regulatory sites that
      could potentially be noncoding drivers. We make LARVA available as a software
      tool and release our highly mutated annotations as an online resource
      (larva.gersteinlab.org). 

PMID- 26304546
TI  - DksA involvement in transcription fidelity buffers stochastic epigenetic change.
AB  - DksA is an auxiliary transcription factor that interacts with RNA polymerase and
      influences gene expression. Depending on the promoter, DksA can be a positive or
      negative regulator of transcription initiation. Moreover, DksA has a substantial
      effect on transcription elongation where it prevents the collision of
      transcription and replication machineries, plays a key role in maintaining
      transcription elongation when translation and transcription are uncoupled and has
      been shown to be involved in transcription fidelity. Here, we assessed the role
      of DksA in transcription fidelity by monitoring stochastic epigenetic switching
      in the lac operon (with and without an error-prone transcription slippage
      sequence), partial phenotypic suppression of a lacZ nonsense allele, as well as
      monitoring the number of lacI mRNA transcripts produced in the presence and
      absence of DksA via an operon fusion and single molecule fluorescent in situ
      hybridization studies. We present data showing that DksA acts to maintain
      transcription fidelity in vivo and the role of DksA seems to be distinct from
      that of the GreA and GreB transcription fidelity factors. 

PMID- 26304547
TI  - RAG-3D: a search tool for RNA 3D substructures.
AB  - To address many challenges in RNA structure/function prediction, the
      characterization of RNA's modular architectural units is required. Using the RNA
      As-Graphs (RAG) database, we have previously explored the existence of secondary
      structure (2D) submotifs within larger RNA structures. Here we present RAG-3D-a
      dataset of RNA tertiary (3D) structures and substructures plus a web-based search
      tool-designed to exploit graph representations of RNAs for the goal of searching
      for similar 3D structural fragments. The objects in RAG-3D consist of 3D
      structures translated into 3D graphs, cataloged based on the connectivity between
      their secondary structure elements. Each graph is additionally described in terms
      of its subgraph building blocks. The RAG-3D search tool then compares a query RNA
      3D structure to those in the database to obtain structurally similar structures
      and substructures. This comparison reveals conserved 3D RNA features and thus may
      suggest functional connections. Though RNA search programs based on similarity in
      sequence, 2D, and/or 3D structural elements are available, our graph-based search
      tool may be advantageous for illuminating similarities that are not obvious;
      using motifs rather than sequence space also reduces search times considerably.
      Ultimately, such substructuring could be useful for RNA 3D structure prediction,
      structure/function inference and inverse folding. 

PMID- 26304548
TI  - Structural basis for the Smad5 MH1 domain to recognize different DNA sequences.
AB  - Smad proteins are important intracellular mediators of TGF-beta signalling, which
      transmit signals directly from cell surface receptors to the nucleus. The MH1
      domain of Smad plays a key role in DNA recognition. Two types of DNA sequence
      were identified as Smad binding motifs: the Smad binding element (SBE) and the GC
      rich sequence. Here we report the first crystal structure of the Smad5 MH1 domain
      in complex with the GC-rich sequence. Compared with the Smad5-MH1/SBE complex
      structure, the Smad5 MH1 domain contacts the GC-rich site with the same beta
      hairpin, but the detailed interaction modes are different. Conserved beta-hairpin
      residues make base specific contacts with the minimal GC-rich site, 5'-GGC-3'.
      The assembly of Smad5-MH1 on the GC-rich DNA also results in distinct DNA
      conformational changes. Moreover, the crystal structure of Smad5-MH1 in complex
      with a composite DNA sequence demonstrates that the MH1 domain is targeted to
      each binding site (GC-rich or SBE) with modular binding modes, and the length of
      the DNA spacer affects the MH1 assembly. In conclusion, our work provides the
      structural basis for the recognition and binding specificity of the Smad MH1
      domain with the DNA targets. 

PMID- 26304550
TI  - Crystal structure of the full-length bacterial selenocysteine-specific elongation
      factor SelB.
AB  - Selenocysteine (Sec), the 21(st) amino acid in translation, uses its specific
      tRNA (tRNA(Sec)) to recognize the UGA codon. The Sec-specific elongation factor
      SelB brings the selenocysteinyl-tRNA(Sec) (Sec-tRNA(Sec)) to the ribosome,
      dependent on both an in-frame UGA and a Sec-insertion sequence (SECIS) in the
      mRNA. The bacterial SelB binds mRNA through its C-terminal region, for which
      crystal structures have been reported. In this study, we determined the crystal
      structure of the full-length SelB from the bacterium Aquifex aeolicus, in complex
      with a GTP analog, at 3.2-A resolution. SelB consists of three EF-Tu-like domains
      (D1-3), followed by four winged-helix domains (WHD1-4). The spacer region,
      connecting the N- and C-terminal halves, fixes the position of WHD1 relative to
      D3. The binding site for the Sec moiety of Sec-tRNA(Sec) is located on the
      interface between D1 and D2, where a cysteine molecule from the crystallization
      solution is coordinated by Arg residues, which may mimic Sec binding. The Sec
      binding site is smaller and more exposed than the corresponding site of EF-Tu.
      Complex models of Sec-tRNA(Sec), SECIS RNA, and the 70S ribosome suggest that the
      unique secondary structure of tRNA(Sec) allows SelB to specifically recognize
      tRNA(Sec) and characteristically place it at the ribosomal A-site. 

PMID- 26304549
TI  - DREAMing: a simple and ultrasensitive method for assessing intratumor epigenetic
      heterogeneity directly from liquid biopsies.
AB  - Many cancers comprise heterogeneous populations of cells at primary and
      metastatic sites throughout the body. The presence or emergence of distinct
      subclones with drug-resistant genetic and epigenetic phenotypes within these
      populations can greatly complicate therapeutic intervention. Liquid biopsies of
      peripheral blood from cancer patients have been suggested as an ideal means of
      sampling intratumor genetic and epigenetic heterogeneity for diagnostics,
      monitoring and therapeutic guidance. However, current molecular diagnostic and
      sequencing methods are not well suited to the routine assessment of epigenetic
      heterogeneity in difficult samples such as liquid biopsies that contain
      intrinsically low fractional concentrations of circulating tumor DNA (ctDNA) and
      rare epigenetic subclonal populations. Here we report an alternative approach,
      deemed DREAMing (Discrimination of Rare EpiAlleles by Melt), which uses semi
      limiting dilution and precise melt curve analysis to distinguish and enumerate
      individual copies of epiallelic species at single-CpG-site resolution in
      fractions as low as 0.005%, providing facile and inexpensive ultrasensitive
      assessment of locus-specific epigenetic heterogeneity directly from liquid
      biopsies. The technique is demonstrated here for the evaluation of epigenetic
      heterogeneity at p14(ARF) and BRCA1 gene-promoter loci in liquid biopsies
      obtained from patients in association with non-small cell lung cancer (NSCLC) and
      myelodysplastic/myeloproliferative neoplasms (MDS/MPN), respectively. 

PMID- 26304551
TI  - A unique uracil-DNA binding protein of the uracil DNA glycosylase superfamily.
AB  - Uracil DNA glycosylases (UDGs) are an important group of DNA repair enzymes,
      which pioneer the base excision repair pathway by recognizing and excising uracil
      from DNA. Based on two short conserved sequences (motifs A and B), UDGs have been
      classified into six families. Here we report a novel UDG, UdgX, from
      Mycobacterium smegmatis and other organisms. UdgX specifically recognizes uracil
      in DNA, forms a tight complex stable to sodium dodecyl sulphate, 2
      mercaptoethanol, urea and heat treatment, and shows no detectable uracil
      excision. UdgX shares highest homology to family 4 UDGs possessing Fe-S cluster.
      UdgX possesses a conserved sequence, KRRIH, which forms a flexible loop playing
      an important role in its activity. Mutations of H in the KRRIH sequence to S, G,
      A or Q lead to gain of uracil excision activity in MsmUdgX, establishing it as a
      novel member of the UDG superfamily. Our observations suggest that UdgX marks the
      uracil-DNA for its repair by a RecA dependent process. Finally, we observed that
      the tight binding activity of UdgX is useful in detecting uracils in the genomes.

PMID- 26304552
TI  - Diversity of Arbuscular Mycorrhizal Fungi in a Brazilian Atlantic Forest
      Toposequence.
AB  - The diversity of arbuscular mycorrhizal fungi (AMF) was studied in the Atlantic
      Forest in Serra do Mar Park (SE Brazil), based on seven host plants in
      relationship to their soil environment, altitude and seasonality. The studied
      plots along an elevation gradient are located at 80, 600, and 1,000 m. Soil
      samples (0-20 cm) were collected in four seasons from SE Brazilian winter 2012 to
      autumn 2013. AMF spores in rhizosperic soils were morphologically classified and
      chemical, physical and microbiological soil caracteristics were determined. AMF
      diversity in roots was evaluated using the NS31/AM1 primer pair, with subsequent
      cloning and sequencing. In the rhizosphere, 58 AMF species were identified. The
      genera Acaulospora and Glomus were predominant. However, in the roots, only 14
      AMF sequencing groups were found and all had high similarity to Glomeraceae. AMF
      species identities varied between altitudes and seasons. There were species that
      contributed the most to this variation. Some soil characteristics (pH, organic
      matter, microbial activity and microbial biomass carbon) showed a strong
      relationship with the occurrence of certain species. The highest AMF species
      diversity, based on Shannon's diversity index, was found for the highest
      altitude. Seasonality did not affect the diversity. Our results show a high AMF
      diversity, higher than commonly found in the Atlantic Forest. The AMF detected in
      roots were not identical to those detected in rhizosperic soil and differences in
      AMF communities were found in different altitudes even in geographically close
      lying sites. 

PMID- 26304553
TI  - Bi-crystallographic lattice structure directs grain boundary motion under shear
      stress.
AB  - Shear stress driven grain boundary (GB) migration was found to be a ubiquitous
      phenomenon in small grained polycrystalline materials. Here we show that the GB
      displacement shift complete (DSC) dislocation mechanism for GB shear coupled
      migration is still functioning even if the geometry orientation of the GBs
      deviates a few degrees from the appropriate coincidence site lattice (CSL) GBs.
      It means that any large angle GB can have a considerable chance to be such a "CSL
      related GB" for which the shear coupled GB migration motion can happen by the GB
      DSC dislocation mechanism. We conclude that the CSL-DSC bi-crystallographic
      lattice structure in GB is the main reason that GB can migrate under shear
      stress. 

PMID- 26304554
TI  - Animal models for the study of HCV.
AB  - The development and evaluation of effective therapies and vaccines for the
      hepatitis C virus (HCV) and the study of its interactions with the mammalian host
      have been hindered for a long time by the absence of suitable small animal
      models. Immune compromised mouse models that recapitulate the complete HCV life
      cycle have been useful to investigate many aspects of the HCV life cycle
      including antiviral interventions. However, HCV has a high propensity to
      establish persistence and associated histopathological manifestations such as
      steatosis, fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Better
      understanding of these processes requires the development of a permissive and
      fully immunocompetent small animal model. In this review we summarize the in vivo
      models that are available for the study of HCV. 

PMID- 26304556
TI  - Efficacy of progesterone for moderate to severe traumatic brain injury: a meta
      analysis of randomized clinical trials.
AB  - Progesterone has been shown to have neuroprotective effects in multiple animal
      models of brain injury, whereas the efficacy and safety in patients with
      traumatic brain injury (TBI) remains contentious. Here, a total of seven
      randomized controlled trials (RCTs) with 2492 participants were included to
      perform this meta-analysis. Compared with placebo, there was no significant
      decrease to be found in the rate of death or vegetative state for patients with
      acute TBI (RR = 0.88, 95%CI = 0.70, 1.09, p = 0.24). Furthermore, progesterone
      was not associated with good recovery in comparison with placebo (RR = 1.00,
      95%CI = 0.88, 1.14, p = 0.95). Together, our study suggested that progesterone
      did not improve outcomes over placebo in the treatment of acute TBI. 

PMID- 26304557
TI  - Violence against Doctors: The Class Wars.
AB  - Medical practice is currently at crossroads due to several ills that have crept
      into the profession. The malaise may have its genesis traced down right from the
      time of entrance into medical school due at least in part to inadequacy and lack
      of contemporariness in current medical curricula. There could be several
      limitations of the medical course at present. The first problem is that rapid
      technological advances in the practice of medicine have led to an exponential
      increase in the amount of information and skills that needs to be acquired by the
      student. Broadly it is a question of dropping vestigial knowledge and re
      prioritization of education according to the requirement of the day. The second
      problem is the alienation of the prospective physician from the society. However,
      perhaps the most alarming problem is lack of inculcation of empathy, rather a
      steady decline in its level over the course of medical school. We discuss how
      these issues can be appropriately addressed in a new curriculum. 

PMID- 26304555
TI  - In Vivo Analysis of Troponin C Knock-In (A8V) Mice: Evidence that TNNC1 Is a
      Hypertrophic Cardiomyopathy Susceptibility Gene.
AB  - BACKGROUND: Mutations in thin-filament proteins have been linked to hypertrophic
      cardiomyopathy, but it has never been demonstrated that variants identified in
      the TNNC1 (gene encoding troponin C) can evoke cardiac remodeling in vivo. The
      goal of this study was to determine whether TNNC1 can be categorized as an
      hypertrophic cardiomyopathy susceptibility gene, such that a mouse model can
      recapitulate the clinical presentation of the proband. METHODS AND RESULTS: The
      TNNC1-A8V proband diagnosed with severe obstructive hypertrophic cardiomyopathy
      at 34 years of age exhibited mild-to-moderate thickening in left and right
      ventricular walls, decreased left ventricular dimensions, left atrial
      enlargement, and hyperdynamic left ventricular systolic function. Genetically
      engineered knock-in (KI) mice containing the A8V mutation (heterozygote=KI-TnC
      A8V(+/-); homozygote=KI-TnC-A8V(+/+)) were characterized by echocardiography and
      pressure-volume studies. Three-month-old KI-TnC-A8V(+/+) mice displayed decreased
      ventricular dimensions, mild diastolic dysfunction, and enhanced systolic
      function, whereas KI-TnC-A8V(+/-) mice displayed cardiac restriction at 14 months
      of age. KI hearts exhibited atrial enlargement, papillary muscle hypertrophy, and
      fibrosis. Liquid chromatography-mass spectroscopy was used to determine
      incorporation of mutant cardiac troponin C (~ 21%) into the KI-TnC-A8V(+/-)
      cardiac myofilament. Reduced diastolic sarcomeric length, increased shortening,
      and prolonged Ca(2+) and contractile transients were recorded in intact KI-TnC
      A8V(+/-) and KI-TnC-A8V(+/+) cardiomyocytes. Ca(2+) sensitivity of contraction in
      skinned fibers increased with mutant gene dose: KI-TnC-A8V(+/+)>KI-TnC-A8V(+/
      )>wild-type, whereas KI-TnC-A8V(+/+) relaxed more slowly on flash photolysis of
      diazo-2. CONCLUSIONS: The TNNC1-A8V mutant increases the Ca(2+)-binding affinity
      of the thin filament and elicits changes in Ca(2+) homeostasis and cellular
      remodeling, which leads to diastolic dysfunction. These in vivo alterations
      further implicate the role of TNNC1 mutations in the development of
      cardiomyopathy.

PMID- 26304558
TI  - BRIGHT HORIZONS for Bivalirudin? EUROMAXimizing benefits of bleeding risk but
      catching a MATRIX of HEAT for stent thrombosis.

PMID- 26304559
TI  - A new echocardiographic index on the horizon: Has the solution finally appeared?

PMID- 26304560
TI  - Setting global standards in adult echocardiography: Where are we?

PMID- 26304561
TI  - Prevalence, treatments and outcomes of coronary artery disease in Indians: A
      systematic review.
AB  - AIM: To conduct a systematic review on the prevalence, risk factors, treatments
      and outcomes of Coronary Artery Disease (CAD) in Indians. METHODS AND RESULTS: We
      conducted a systematic review of studies in Indians with CAD from Jan 1969 to Oct
      2012. Initial search yielded 3885 studies and after review 288 observational
      studies were included. The prevalence of CAD in urban areas was 2.5%-12.6% and in
      rural areas, 1.4%-4.6%. The prevalence of risk factors was: smoking (8.9-40.5%),
      hypertension (13.1-36.9%) and diabetes mellitus (0.2-24.0%). The median time to
      reach hospital after an MI was 360 min. In hospital rates of drug use were:
      antiplatelets 68%-97.9%, beta blockers 47.3%-65.8% and ACEIs 27.8-56.8%.
      CONCLUSIONS: In this first systematic review of CAD in India, prevalence of risk
      factors is high, treatments delayed and use of evidence based treatments
      variable.

PMID- 26304562
TI  - Comparison of anti-thrombotic strategies using Bivalirudin, Heparin plus
      Glycoprotein IIb/IIIa inhibitors and Unfractionated Heparin Monotherapy for
      patients undergoing percutaneous coronary intervention - A single centre
      observational study.
AB  - AIMS: The study was planned to compare Anti-thrombotic strategies for patients
      undergoing PCI in a real world population with an emphasis on occurrence of major
      bleeding, composite ischemic end points and economic outcomes. METHODS: The
      present study is a single center, prospective, observational study in consecutive
      patients undergoing PCI at Fortis Escorts Heart Institute (FEHI) and describes
      Authors' experience with three different Anti-Thrombotic Strategies in a real
      world population. Patients were consecutively enrolled in the study and the
      choice of Anti-thrombotic strategy was left to individual operator(s) based on
      their own clinical judgment and patient's affordability. No specific
      inclusion/exclusion criteria were specified on the choice of Anti-Thrombotic
      Strategy. RESULTS: A total 1453 patients were consecutively enrolled into the
      study and were followed telephonically after 30 days. 252 patients were treated
      with Bivalirudin (Angiomax) during PCI (17.3%), 430 (29.6%) patients were treated
      with Heparin plus GPI & remaining 771 (53.1%) were treated with Heparin
      monotherapy. Incidence of major bleeding was lowest in patients treated with
      Bivalirudin (1.59%) when compared to Heparin plus GPI (3.49%) and Heparin
      monotherapy (5.97%), p = 0.005 Bivalirudin vs. Heparin Monotherapy, and p =
      0.145, Bivalirudin vs. Heparin + GPI. No bleeding was observed in STEMI patients
      treated with Bivalirudin compared to 7.4% in patients treated with GPI and 14.3%
      in patients treated with UFH. Similarly non-access site bleeding was lowest in
      patients treated with Bivalirudin. Only 4 patients (1.6%) treated with
      Bivalirudin required Blood transfusion compared to 25 in Heparin plus GPI (5.8%)
      and 38 (5%) in Heparin Monotherapy arm. In Composite Ischemic end-points, no "All
      cause Mortality" was observed in Bivalirudin group compared to 2.8% in Heparin
      plus GPI. Early stent thrombosis was seen in 1 patient with Heparin plus GPI and
      none with Heparin monotherapy and Bivalirudin group. None of the patients
      underwent TLR (target lesion revascularization) and TVR (target vessel
      revascularization) within 30 days post procedure other than one early stent
      thrombosis reported with Heparin plus GPI. Cost of blood product transfusion was
      lower with Bivalirudin as compared to Heparin plus GP IIb/IIIa arm (p = 0.01) and
      with Heparin alone (p = 0.001). Due to lower complications including blood
      transfusions and reduced hospital stay in Bivalirudin group, these benefits
      outweigh the incremental cost due to higher acquisition cost of the drug.
      CONCLUSION: Bivalirudin use during PCI is associated with a distinct advantage of
      having lower access site and non-access site bleeding without compromising on the
      efficacy. We observed a reduction in blood transfusions, hospital stay and
      mortality for patients treated with Bivalirudin compared with Heparin plus GPI or
      Heparin Monotherapy. Bivalirudin can be safely adopted into our Institutional
      protocol for the treatment of high risk PCI such as STEMI, ACS, and Complex
      elective PCI.

PMID- 26304563
TI  - Prognostic significance of NT-proBNP, 3D LA volume and LV dyssynchrony in
      patients with acute STEMI undergoing primary percutaneous intervention.
AB  - OBJECTIVES: The aim of the present study was to assess the short term prognostic
      significance of N-terminal pro BNP (NT-proBNP), 3D left atrial volume (LAV) and
      left ventricular (LV) dyssynchrony in patients of acute ST-elevation myocardial
      infarction (STEMI) who underwent primary Percutaneous intervention (PCI).
      BACKGROUND: NT-proBNP, LV dyssynchrony and LAV in patients with acute coronary
      syndrome have been associated with PCI outcomes and predict the short and long
      term prognosis. METHODS: This study consisted of 142 patients with a first STEMI
      who underwent primary PCI. Baseline echocardiographic data was collected at
      admission and at 6 months follow up. Left ventricular dyssynchrony was measured
      by tissue Doppler imaging and LAV by real time 3D-echocardiography, plasma NT
      proBNP levels were estimated between 72 and 96 h of admission. RESULTS: During
      study period 3 patients expired and 4 developed congestive heart failure (CHF).
      Baseline NT-proBNP and LV dyssynchrony correlated with LV size and LV ejection
      fraction (LVEF) at baseline and during follow up. Patients with higher NT-proBNP
      levels and higher LV dyssynchrony showed significant increase in LV size with
      decrease in LVEF during follow-up. Baseline Left atrial volume index (LAVI)
      showed significant correlation with LV size but no association with LVEF at
      baseline and during follow-up. CONCLUSIONS: Higher levels of NT-proBNP and higher
      LV dyssynchrony can predict patients with increase in LV size, worsening of LV
      systolic and diastolic function during follow-up. Patients with higher NT-proBNP
      levels at baseline developed CHF during follow-up.

PMID- 26304564
TI  - Cardiac syndrome X: Clinical characteristics revisited.
AB  - BACKGROUND: Cardiac syndrome X includes a heterogenous group of patients with
      angina but normal epicardial coronaries in angiography. OBJECTIVE: Our objective
      was to study the clinical characteristics of patients with cardiac syndrome X.
      METHODS: Data of patients who underwent coronary angiography over a period of one
      year was retrospectively analyzed. Those with normal or non-obstructive
      coronaries in angiography with chest pain were included in this study. RESULTS:
      1203 patients underwent coronary angiography during the study period. 105 (8.7%)
      patients fulfilled the inclusion criteria. There were 52 (49.5%) males and 53
      (50.5%) females including 31 (29.5%) postmenopausal women. Many patients had
      atherosclerotic risk factors. Typical angina and atypical chest pain were
      reported by 63 (60%) and 42 (40%) patients, respectively. ECG was normal in 46
      (43.8%) and abnormal in 59 (56.2%) patients. The most common abnormal finding in
      ECG was ST-T changes seen in 49 (46.7%) patients. Regional wall motion
      abnormality with mild left ventricular systolic dysfunction was seen in 4 (3.8%)
      patients while 101 (96.2%) patients had normal ventricular function in
      echocardiography. TMT was positive for inducible ischemia in 35 (33.3%) patients
      and inconclusive in 10 (9.5%) patients. Angiography showed normal epicardial
      coronaries in 85 (80.9%) patients. CONCLUSIONS: Cardiac syndrome X constitutes a
      significant subset of patients undergoing coronary angiography. It is essential
      to identify and treat them specifically for microvascular angina. Many of them
      have atherosclerotic risk factors but their presentation is different from those
      with obstructive coronaries.

PMID- 26304565
TI  - Relationship between different cardiovascular risk scores and measures of
      subclinical atherosclerosis in an Indian population.
AB  - BACKGROUND: Relative accuracy of the various currently available cardiovascular
      (CV) risk assessment algorithms in Indian patients is not known. METHODS: This
      study included 194 consecutive patients (mean age 49.6 +/- 10.3 years, 84.5%
      males) attending a CV disease prevention clinic at a tertiary center in north
      India. Four risk assessment models [Framingham Risk score (RiskFRS), American
      College of Cardiology/American Heart Association pooled cohort equations
      (RiskACC/AHA), the 3rd iteration of Joint British Societies' risk calculator
      (RiskJBS) and the World Health Organization/International Society of Hypertension
      risk prediction charts (RiskWHO)] were applied. The estimated risk scores were
      correlated with carotid intima-media thickness (CIMT) and coronary calcium score
      (CCS) using nonparametric statistics (Chi-square test, Kruskal-Wallis test and
      Spearman rank correlation). RESULTS: Overall, RiskACC/AHA and RiskWHO
      significantly underestimated CV risk as compared to RiskJBS and RiskFRS, with
      RiskJBS being the least likely to underestimate the risk (patients with coronary
      artery disease who were found to have >=20% CV risk- 21.4% with RiskACC/AHA,
      17.9% with RiskWHO, 41.4% with RiskFRS, and 58.6% with RiskJBS). Further, only
      RiskJBS and RiskFRS, but not RiskACC/AHA and RiskWHO, demonstrated consistent
      relationship with CIMT and CCS (Spearman rho 0.45 and 0.46 for RiskJBS and 0.39
      and 0.36 for RiskFRS for CIMT and CCS respectively, all p values < 0.001).
      CONCLUSIONS: The present study shows that in Indian subjects RiskJBS appears to
      provide the most accurate estimation of CV risk. It least underestimates the risk
      and has the best correlation with CIMT and CCS. However, large-scale prospective
      studies are needed to confirm these findings.

PMID- 26304566
TI  - Surucu index and others.
AB  - BACKGROUND: In this study, we have aimed to evaluate the correlation between
      echocardiographic parameters that test systolic and diastolic function together.
      METHOD: The study population was divided into two groups according to Vp. Group-1
      (n = 103) represented the control group (Vp > 50 cm/s) and group-2 (n = 86)
      represented patients with systolic and diastolic dysfunctions together (Vp <= 50
      cm/s). The echocardiographic parameters that evaluate systolic and diastolic
      function together, such as the Tei and the Surucu indices, were compared between
      the groups. RESULTS: In group-2, the Tei index was higher (p = 0.001) and the
      Surucu index was lower (p < 0.001). We also showed that the Tei and Surucu
      indices were significantly and negatively correlated. That is, as the Surucu
      index decreases, the Tei index increases (p = 0.001). CONCLUSION: Vp is an index
      more affected by diastolic parameters but rarely by systolic parameters because
      it is measured at diastolic period. The Tei index, on the other hand, is affected
      by preload variables and needs two different heart cycles for calculation. The
      Modified Tei index, however, has limited diagnostic value because of high inter
      observer variability. In this study, the usability of the Surucu index is shown
      in comparison with other indices used for this purpose. Considering that it is
      less affected by preload variables, can be calculated over a single heart cycle,
      and has the ability to test variables of both systolic and diastolic periods
      unlike Vp. We postulate that the Surucu index is more usable and reliable.

PMID- 26304567
TI  - Cardiometabolic risk factors in the Agarwal business community in India: Jaipur
      Heart Watch-6.
AB  - BACKGROUND: Agarwal is one of the largest business communities in India. To
      determine prevalence of cardiovascular risk factors and their distribution
      according to educational status (ES) in this community we performed a study.
      METHODS: 1781 (men 1039, women 742) of 2500 selected subjects (71.2%) were
      evaluated and fasting blood sample obtained in 1130. RESULTS: Age-adjusted
      prevalence of risk factors was tobacco use 12.2%, sedentary habits 54.2%,
      overweight/obesity 54.4%, obesity 19.5%, abdominal obesity 61.2%, hypertension
      36.0%, diabetes 19.2%, hypercholesterolemia >=200 mg/dl 25.8%, low HDL
      cholesterol 29.2%, hypertriglyceridemia 32.8% and metabolic syndrome 22.3%. Low
      ES subjects had significantly greater prevalence of sedentary habits, low
      fruit/vegetable intake, hypertension, low HDL cholesterol and diabetes.
      CONCLUSIONS: Cardiometabolic risk factors are highly prevalent in the Agarwal
      business community. Prevalence is greater in subjects with low educational
      status.

PMID- 26304569
TI  - Infiltrating cardiac lipoma presenting as ventricular tachycardia in a young
      adult.

PMID- 26304568
TI  - Strategies for the coronary surgeon to remain "competitive and co-operative" in
      the PCI era.
AB  - BACKGROUND: The advent of percutaneous intervention has made surgical treatment
      of coronary artery disease less favored by patients though the evidence that
      supports CABG in certain patient subsets is strong. METHODS: Literature review
      was done using Pubmed, Scopus, Google and Google Scholar with MeSH terms-coronary
      artery bypass grafting, internal mammary artery, drug eluting stent, stroke,
      myocardial revascularization. RESULTS: The adoption of evolving techniques like
      anaortic off pump grafting, bilateral internal mammary artery use, hybrid and
      minimally invasive coronary revascularization techniques, intra-operative graft
      assessment, and heart team approach can lead to better outcomes following surgery
      as is evidenced by recent literature. CONCLUSIONS: Though the adoptability of the
      newer strategies may vary between centers a close coalition between coronary
      surgeons and cardiologists would ensure that the management of coronary artery
      disease is based on evidence for the benefit of the patient.

PMID- 26304570
TI  - An unusual ECG pattern in restrictive cardimyopathy.
AB  - Restrictive cardiomyopathy is the least common type of primary cardiomyopathies.
      Electrocardiographic recording is abnormal in 99% of patients with RCM. Biatrial
      enlargement, obliquely elevated ST segment with notched or biphasic late peaking
      T waves are considered characteristic ECG finding. Significant ST depression with
      T inversion mimicking subendocardial ischemia has also been reported in patients
      with RCM and is even suggested as a predictor of sudden cardiac death. We noted a
      similar ECG pattern in a 16 yr girl with Idiopathic restrictive cardiomyopathy.
      Coronaries were normal, stress perfusion imaging did not show any perfusion
      defect. This diffuse resting ST depression with T inversion in precordial &
      inferior leads along with ST elevation in aVR was persistent for more than six
      months. 

PMID- 26304571
TI  - Repair of coarctation of aorta with preservation of blood supply to upper limb.
AB  - In this report, we present a modified technique of extended resection and end-to
      end anastomosis of aorta for repair of coarctation of aorta. The advantages of
      this technique are a larger tension free anastomosis without compromising the
      blood supply into the left subclavian artery. 

PMID- 26304572
TI  - Bilateral outflow obstructions without ventricular septal defect in an adult:
      Illustrated by real-time 3D echocardiography.
AB  - Double-chambered right ventricle with discrete subaortic stenosis without
      ventricular septal defect is rare in adults. This report shows incremental value
      of 3D echocardiography in delineating the pathoanatomy of these lesions. 

PMID- 26304573
TI  - Severe biventricular hypertrophy mimicking infiltrative cardiomyopathy in old man
      with pulmonary stenosis and systemic hypertension.
AB  - Hypertrophic biventricular cardiomyopathy is a rare finding and generally caused
      by systemic infiltrative diseases. Its association with pulmonary stenosis in
      same patient is even rarer. We report a case report of male patient with
      biventricular hypertrophy coexisting with pulmonary valve stenosis and systemic
      hypertension. 

PMID- 26304574
TI  - Atrial flutter ablation in a case of diuretic resistant constrictive
      pericarditis.
AB  - We present a 66 year old gentleman with constrictive pericarditis and persistent
      atrial flutter. Initial management with oral loop diuretics was successful until
      he developed persistent atrial flutter. Once in atrial flutter the patient
      developed progressive signs of right heart failure resistant to high dose
      intravenous loop diuretics. He was referred to a tertiary electrophysiology
      service where he underwent successful isthmus catheter ablation and reverted to
      sinus rhythm. His responsiveness to diuretics improved immediately. His symptoms
      improved and he was discharged 48 h later on oral diuretics. He remains well one
      month after discharge. This is the first reported case of symptomatic improvement
      in a patient with constrictive pericarditis and persistent atrial flutter with
      targeted treatment of the dysrhythmia. This offers a possible short-term
      palliation option in a group of patients where definitive surgical management
      carries too high a risk. 

PMID- 26304575
TI  - A unique complication of the GuideZilla guide extension support catheter and the
      risk of stent stripping in interventional & endovascular interventions.
AB  - Supporting catheters in percutaneous stenting of anatomically difficult coronary
      lesions are utilized by interventional cardiologists. The GuideZilla guide
      extension catheter is designed for deep seating in coronary arteries to provide
      extra guidance support for equipment delivery during difficult coronary
      interventions or for coaxial alignment in tortuous vessels. There are limited
      GuideZilla-related complications reported in the literature. We present a
      challenging case of a left main and left anterior descending artery dissection,
      complicated with stent stripping off the delivery balloon by the GuideZilla
      support catheter. 

PMID- 26304576
TI  - Missed Kawasaki disease in childhood presenting as myocardial infarction in
      adults.
AB  - Kawasaki disease (KD) is an acute, self-limited vasculitis that occurs in young
      children and was first described by Japanese pediatrician Tomisaku Kawasaki in
      1967. Although originally thought to be a rare condition, KD has become the most
      common cause of acquired heart disease in the pediatric population in developed
      countries. The majority of patients with KD appear to have a benign prognosis,
      but a subset of patients with coronary artery aneurysms are at risk for ischemic
      events and require lifelong treatment. In the 4 decades since the initial
      recognition of KD, the number of patients reaching adulthood has continued to
      grow. Adult cardiologists will be increasingly involved in the management of
      these patients. Currently, there are no established guidelines for the evaluation
      and treatment of adult patients who have had KD. We report 4 most probable cases
      of KD missed in childhood and presented as acute coronary syndrome in adulthood. 

PMID- 26304577
TI  - A rare case of 'superdominant' single coronary artery.
AB  - A 45 year male patient with no risk factors and no associated cardiac anomaly
      presented to us with exertional chest pain since 10 years. During coronary
      angiography, we were unable to intubate the left main coronary artery.
      Cannulation of the right coronary ostium showed a 'superdominant' Right coronary
      artery, which initially followed the course of the normal right coronary artery,
      then proceeded via a posterolateral segment into the course of the normal left
      circumflex artery, and finally followed the course of the normal left anterior
      descending artery (Images 1-3).CT coronary angiogram confirmed the findings
      (Images4-5). Intramyocardial bridging was also seen which explained the angina.
      This subtype is named type R-IA according to Lipton's classification and is by
      far the most rare type of single coronary artery with an incidence of 0.0008%.
      Some patients may present with myocardial ischemia or stable angina. The exact
      mechanism is unknown but may be related to intramyocardial bridging or coursing
      of epicardial arteries between great arteries. 

PMID- 26304578
TI  - The classical "R-on-T" phenomenon.
AB  - The polymorphic ventricular tachycardia (PVT) is uncommon arrhythmia with
      multiple causes and has been classified according to whether they are associated
      with long QT interval or normal QT. Whereas "Torsade de pointes (TdP)" is an
      uncommon and distinctive form of PVT occurring in a setting of prolonged QT
      interval, which may be congenital or acquired (congenital or acquired), "PVT with
      normal QT" is associated with myocardial ischemia, electrolyte abnormalities
      (hypokalemia), mutations of the cardiac sodium channel (Brugada syndrome), and
      the ryanodine receptor (catecholaminergic PVT). This distinction is crucial
      because of the differing etiologies and management of these arrhythmias.
      Moreover, the PVT in the setting of acute MI generally occurs during the
      hyperacute phase, is related to ischemia ("ischemic PVT") and is not associated
      with QT prolongation. It is triggered by ventricular extrasystoles with very
      short coupling interval (the "R-on-T" phenomenon) and is not pause-dependent.
      However, recently there has been described a new PVT during the "healing phase"
      of MI in patients with no evidence of ongoing ischemia and following excessive QT
      prolongation, the electrophysiologic abnormality being a "pause-dependent infarct
      related TdP" due to a LQTS in healing MI patients. Therefore, "ischemic PVT"
      differs from "infarct-related TdP" in terms of pathophysiology and ECG
      manifestations. 

PMID- 26304579
TI  - An unusual cause of left ventricular outflow tract obstruction.
AB  - Left ventricular outflow tract obstruction (LVOTO) has been reported with bio
      prosthetic and mechanical mitral valves (MV), though it is more common with the
      former. The obstruction can be dynamic or fixed. We hereby report a case of fixed
      LVOTO following bio-prosthetic MV replacement (MVR). 

PMID- 26304580
TI  - Duration of antiplatelet therapy cessation before coronary artery bypass surgery:
      Relation with platelet count.
AB  - As of now, no study or data is available to determine the period of
      discontinuation of antiplatelet therapy and the timing of elective surgery in
      clopidogrel treated patients. The 2011 ACCF/AHA Guidelines have a Class-I
      recommendation for withdrawing clopidogrel for 5 days before elective coronary
      artery bypass grafting. However, 5 days period may not suit all patients as
      platelet count varies from 150 * 10(9)/L to 450 * 10(9)/L. Based on our
      retrospective data analysis, we have proposed a hypothesis to determine no of
      days of discontinuation of antiplatelet therapy while taking in consideration the
      basal count and life-span of platelets. 

PMID- 26304581
TI  - Vascular plugs - A key companion to Interventionists - 'Just Plug it'.
AB  - Vascular plugs are ideally suited to close extra-cardiac, high flowing vascular
      communications. The family of vascular plugs has expanded. Vascular plugs in
      general have a lower profile and the newer variants can be delivered even through
      a diagnostic catheter. These features make them versatile and easy to use. The
      Amplatzer vascular plugs are also used for closing intracardiac defects including
      coronary arterio-venous fistula and paravalvular leakage in an off-label fashion.
      In this review, the features of currently available vascular plugs are reviewed
      along with tips and tricks of using them in the cardiac catheterization
      laboratory. 

PMID- 26304582
TI  - Sudden iatrogenic suicidal right ventricle.
AB  - It is important to obtain a good withdrawal pressure tracing while performing
      cardiac catheterization in cases with right ventricular outflow tract (RVOT)
      obstruction to document the site and severity of obstruction. However efforts to
      manipulate the catheter in the RVOT (either to obtain the gradients or to
      position the catheter for an outflow angiogram) can sometimes precipitate severe
      dynamic RVOT obstruction with complete cessation of forward flow leading to life
      threatening hypotension. The following hemodynamic traces highlight this rare
      phenomenon which needs to be borne in mind at all times while performing cardiac
      catheterization in such patients. 

PMID- 26304583
TI  - Mean platelet volume in acute coronary syndrome.

PMID- 26304584
TI  - Government or private practice: Does it really matter in India?

PMID- 26304585
TI  - CT prediction of the Fuhrman grade of clear cell renal cell carcinoma (RCC):
      towards the development of computer-assisted diagnostic method.
AB  - PURPOSE: There are distinct quantifiable features characterizing renal cell
      carcinomas on contrast-enhanced CT examinations, such as peak tumor enhancement,
      tumor heterogeneity, and percent contrast washout. While qualitative visual
      impressions often suffice for diagnosis, quantitative metrics if developed and
      validated can add to the information available from standard of care diagnostic
      imaging. The purpose of this study is to assess the use of quantitative
      enhancement metrics in predicting the Fuhrman grade of clear cell RCC. MATERIALS
      AND METHODS: 65 multiphase CT examinations with clear cell RCCs were utilized, 44
      tumors with Fuhrman grades 1 or 2 and 21 tumors with grades 3 or 4. After tumor
      segmentation, the following data were extracted: histogram analysis of voxel
      based whole lesion attenuation in each phase, enhancement and washout using mean,
      median, skewness, kurtosis, standard deviation, and interquartile range. RESULTS:
      Statistically significant difference was observed in 4 measured parameters
      between grades 1-2 and grades 3-4: interquartile range of nephrographic
      attenuation values, standard deviation of absolute enhancement, as well as
      interquartile range and standard deviation of residual nephrographic enhancement.
      Interquartile range of nephrographic attenuation values was 292.86 HU for grades
      1-2 and 241.19 HU for grades 3-4 (p value 0.02). Standard deviation of absolute
      enhancement was 41.26 HU for grades 1-2 and 34.66 HU for grades 3-4 (p value
      0.03). Interquartile range was 297.12 HU for residual nephrographic enhancement
      for grades 1-2 and 235.57 HU for grades 3-4 (p value 0.02), and standard
      deviation of the same was 42.45 HU for grades 1-2 and 37.11 for grades 3-4 (p
      value 0.04). CONCLUSION: Our results indicate that absolute enhancement is more
      heterogeneous for lower grade tumors and that attenuation and residual
      enhancement in nephrographic phase is more heterogeneous for lower grade tumors.
      This represents an important step in devising a predictive non-invasive model to
      predict the nucleolar grade.

PMID- 26304586
TI  - Endoscopic retrograde cholangiopancreatography in patients with surgically
      altered gastrointestinal anatomy.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically
      altered upper gastrointestinal anatomy, such as Roux-en-Y gastric bypass (RYGB),
      can be more challenging compared to those with a normal anatomy. Detailed
      assessment of cross-sectional imaging features by the radiologist, especially the
      pancreaticobiliary anatomy, strictures, and stones, is very helpful to the
      endoscopist in planning the procedure. In addition, any information on enteral
      anastomoses (for e.g., gastrojejunal strictures and afferent limb obstruction) is
      also very useful. The endoscopist should review the operative note to understand
      the exact anatomy prior to procedure. RYGB, which is performed for medically
      complicated obesity, is the most commonly encountered altered anatomy ERCP
      procedure. Other situations include patients who have had a
      pancreaticoduodenectomy or a hepaticojejunostomy. Balloon-assisted deep
      enteroscopy (single and double-balloon enteroscopy) or rotational endoscopy is
      often used to traverse the length of the intestine to reach the papilla. In
      addition, ERCP in these patients is further challenging due to the oblique
      orientation of the papilla relative to the forward viewing endoscope and the
      limited enteroscopy-length therapeutic accessories that are currently available.
      Overall, reported therapeutic success is approximately 70-75% with a complication
      rate of 3-4%. Alternative approaches include percutaneous transhepatic
      cholangiography, laparoscopy-assisted ERCP, or surgery. Given the complexity,
      ERCP in patients with surgically altered anatomy should be performed in close
      collaboration with body imagers, interventional radiology, and surgical services.

PMID- 26304587
TI  - CADBURE: A generic tool to evaluate the performance of spliced aligners on RNA
      Seq data.
AB  - The fundamental task in RNA-Seq-based transcriptome analysis is alignment of
      millions of short reads to the reference genome or transcriptome. Choosing the
      right tool for the dataset in hand from many existent RNA-Seq alignment packages
      remains a critical challenge for downstream analysis. To facilitate this choice,
      we designed a novel tool for comparing alignment results of user data based on
      the relative reliability of uniquely aligned reads (CADBURE). CADBURE can easily
      evaluate different aligners, or different parameter sets using the same aligner,
      and selects the best alignment result for any RNA-Seq dataset. Strengths of
      CADBURE include the ability to compare alignment results without the need for
      synthetic data such as simulated genomes, alignment regeneration and randomly
      subsampled datasets. The benefit of a CADBURE selected alignment result was
      supported by differentially expressed gene (DEG) analysis. We demonstrated that
      the use of CADBURE to select the best alignment from a number of different
      alignment results could change the number of DEGs by as much as 10%. In
      particular, the CADBURE selected alignment result favors fewer false positives in
      the DEG analysis. We also verified differential expression of eighteen genes with
      RT-qPCR validation experiments. CADBURE is an open source tool
      (http://cadbure.sourceforge.net/). 

PMID- 26304589
TI  - Water Research Sludge Special Issue.

PMID- 26304588
TI  - UCP-3 uncoupling protein confers hypoxia resistance to renal epithelial cells and
      is upregulated in renal cell carcinoma.
AB  - Tumor cells can adapt to a hostile environment with reduced oxygen supply. The
      present study aimed to identify mechanisms that confer hypoxia resistance.
      Partially hypoxia/reoxygenation (H/R)-resistant proximal tubular (PT) cells were
      selected by exposing PT cultures to repetitive cycles of H/R. Thereafter, H/R
      induced changes in mRNA and protein expression, inner mitochondrial membrane
      potential (DeltaPsi(m)), formation of superoxide, and cell death were compared
      between H/R-adapted and control PT cultures. As a result, H/R-adapted PT cells
      exhibited lower H/R-induced hyperpolarization of DeltaPsi(m) and produced less
      superoxide than the control cultures. Consequently, H/R triggered DeltaPsi(m)
      break-down and DNA degradation in a lower percentage of H/R-adapted than control
      PT cells. Moreover, H/R induced upregulation of mitochondrial uncoupling protein
      3 (UCP-3) in H/R-adapted PT but not in control cultures. In addition, ionizing
      radiation killed a lower percentage of H/R-adapted as compared to control cells
      suggestive of an H/R-radiation cross-resistance developed by the selection
      procedure. Knockdown of UCP-3 decreased H/R- and radioresitance of the H/R
      adapted cells. Finally, UCP-3 protein abundance of PT-derived clear cell renal
      cell carcinoma and normal renal tissue was compared in human specimens indicating
      upregulation of UCP-3 during tumor development. Combined, our data suggest
      functional significance of UCP-3 for H/R resistance.

PMID- 26304590
TI  - Electrical and rheological properties of sewage sludge--Impact of the solid
      content.
AB  - Sludge treatment is a multistep process during which sludge is mixed, pumped,
      thickened and dewatered. The total solid content (TSC) increases from a few grams
      to more than a hundred grams per liter and as underlined by the existing
      literature, rheological characteristics are key criteria for sludge management.
      However, these characteristics remain difficult to be determined in-situ and
      professionals are looking for alternative techniques to evaluate them. In that
      context, the potential of electrical measurements has been highlighted (Dieude
      Fauvel et al., 2009, 2014). This paper investigates the additional benefits of
      correlating both rheological and electrical properties for sludge
      characterization within the range of 1-23%TSC. On a rheological point of view,
      results are consistent with previous literature. In parallel, electrical
      impedance spectroscopy allowed us to define an equivalent electrical circuit to
      model the sludge electrical signature. Results highlight that the circuit
      parameters follow two regimes according to the range of solid content, similarly
      to rheological properties. This work opens new insights about sludge
      characterization and treatment monitoring.

PMID- 26304591
TI  - Compressional rheology: A tool for understanding compressibility effects in
      sludge dewatering.
AB  - Water and wastewater treatment sludges exhibit compressible behaviour due to
      flocculation and aggregation. At a critical solids concentration called the gel
      point, which is as low as 1-2 v/v%, a continuous interconnected network of
      particles is formed that can resist an applied load. The applied load (mechanical
      filtration pressure or buoyancy in settling for example) must exceed the network
      strength in order to consolidate the network. The network strength increases with
      solids concentration such that the equilibrium extent of consolidation is a
      function of the applied load. Improved understanding of the nature of
      compressible suspensions can have a significant impact through optimising design
      and operation of sludge handling and dewatering processes. This work gives an
      overview of compressional rheology, which has proven to be a useful tool for
      describing the solid-liquid separation of compressible systems. This is followed
      by three examples where compressibility effects must be taken into account,
      namely the extraction of material properties for extremely compressible
      materials, consolidation and crust formation during constant rate evaporation,
      and the effect of bed height in thickening. 

PMID- 26304592
TI  - Electro-dewatering of wastewater sludge: An investigation of the relationship
      between filtrate flow rate and electric current.
AB  - Compared to conventional dewatering techniques, electrical assisted mechanical
      dewatering, also called electro-dewatering (EDW) is an alternative and an
      effective technology for the dewatering of sewage sludge with low energy
      consumption. The objectives of this study were to evaluate the dewatering
      performance and to determine the influence of the process parameters (e.g.
      applied electric current, applied voltage, and the initial amount of dry solids)
      on the kinetics of EDW-process for activated urban sludge. Also significant
      efforts have been devoted herein to provide comprehensive information about the
      EDW mechanisms and to understand the relationship between these operating
      conditions with regards to develop a qualitative and quantitative understanding
      model of the electro-dewatering process and then produce a robust design
      methodology. The results showed a very strong correlation between the applied
      electric current and the filtrate flow rate and consequently the electro
      dewatering kinetics. A higher applied electric current leads to faster EDW
      kinetics and a higher final dry solids content. In contrast, the results of this
      work showed a significant enhancement of the dewatering kinetics by decreasing
      the mass of the dry solids introduced into the cell (commonly known as the sludge
      loading). 

PMID- 26304593
TI  - Impact of dewatering technologies on specific methanogenic activity.
AB  - Dewatering methods for recuperative thickening and final dewatering can
      potentially impact methanogenic activity and microbial community. This influences
      both the feasibility of recuperative thickening to increase solids residence time
      within a digester, and the utilisation of dewatered digestate as inoculum for new
      digesters. Thickening technology can reduce methanogenic activity through either
      air contact (rotary drum, DAF, or belt filter press), or by lysing cells through
      shear (centrifuge). To assess this, two plants with recuperative thickening
      (rotary drum) in their anaerobic digester, and five without recuperative
      thickening, had specific methanogenic activity tested in all related streams,
      including dewatering feed, thickened return, final cake, and centrate. All plants
      had high speed centrifuges for final dewatering. The digester microbial community
      was also assessed through 16s pyrotag sequencing and subsequent principal
      component analysis (PCA). The specific methanogenic activity of all samples was
      in the expected range of 0.2-0.4 gCOD gVS(-1)d(-1). Plants with recuperative
      thickening did not have lower digester activity. Centrifuge based dewatering had
      a significant and variable impact on methanogenic activity in all samples,
      ranging between 20% and 90% decrease but averaging 54%. Rotary drum based
      recuperative thickening had a far smaller impact on activity, with a 0% per-pass
      drop in activity in one plant, and a 20% drop in another. However, the presence
      of recuperative thickening was a major predictor of overall microbial community
      (PC1, p = 0.0024). Microbial community PC3 (mainly driven by a shift in
      methanogens) was a strong predictor for sensitivity in activity to shear (p =
      0.0005, p = 0.00001 without outlier). The one outlier was related to a plant
      producing the wettest cake (17% solids). This indicates that high solids is a
      potential driver of sensitivity to shear, but that a resilient microbial
      community can also bestow resilience. Sensitivity of methanogens to centrifuging
      does not rule out centrifuges for recuperative thickening (particularly where
      hydrolysis is rate-limiting), but may impose a maximum return rate to avoid
      digester failure.

PMID- 26304594
TI  - Tailoring phase slip events through magnetic doping in superconductor-ferromagnet
      composite films.
AB  - The interplay between superconductivity (SC) and ferromagnetism (FM) when
      embedded together has attracted unprecedented research interest due to very rare
      coexistence of these two phenomena. The focus has been mainly put into the
      proximity induced effects like, coexistence of magnetism and superconductivity,
      higher critical current, triplet superconductivity etc. However, very little
      attention has been paid experimentally to the role of magnetic constituent on
      triggering phase slip processes in the composite films (CFs). We demonstrate that
      less than 1 at.% of magnetic contribution in the CFs can initiate phase slip
      events efficiently. Due to advanced state-of-the-art fabrication techniques,
      phase slip based studies have been concentrated mainly on superconducting
      nanostructures. Here, we employ wide mesoscopic NbGd based CFs to study the phase
      slip processes. Low temperature current-voltage characteristics (IVCs) of CFs
      show stair-like features originated through phase slip events and are absent in
      pure SC films. Depending on the bias current and temperature, distinct regions,
      dominated by Abrikosov type vortex-antivortex (v-av) pairs and phase slip events,
      are observed. The results presented here open a new way to study the phase slip
      mechanism, its interaction with v-av pairs in two dimensions and hence can be
      useful for future photonic and metrological applications. 

PMID- 26304595
TI  - Effect of urine urea nitrogen and protein intake adjusted by using the estimated
      urine creatinine excretion rate on the antiproteinuric effect of angiotensin II
      type I receptor blockers.
AB  - OBJECTIVES: The aim of this study was to determine the role of protein intake on
      proteinuria in chronic kidney disease (CKD), as it is presently not conclusive.
      METHODS: This is a subanalysis of data from an open-label, case-controlled,
      randomized clinical trial on education about low-salt diets (NCT01552954). We
      estimated the urine excretion rate of parameters in a day, adjusted by using the
      equation for estimating urine creatinine excretion, and analyzed the effect of
      urine urea nitrogen (UUN), as well as estimating protein intake on the level of
      albuminuria in hypertensive patients with chronic kidney disease. RESULTS: Among
      174 participants from whom complete 24-h urine specimens were collected, the
      estimates from the Tanaka equation resulted in the highest accuracy for the
      urinary excretion rate of creatinine, sodium, albumin, and UUN. Among 227
      participants, the baseline value of estimated urine albumin excretion (eUalb) was
      positively correlated with the estimated UUN (eUUN) or protein intake according
      to eUUN (P = 0.012 and P = 0.038, respectively). We were able to calculate the
      ratios of eUalb and eUUN in 221 participants and grouped them according to the
      ratio of eUUN during 16-wk trial period. The proportion of patients that achieved
      a decrement of eUalb >=25% during 16 wk with an angiotensin II type I receptor
      blocker (ARB) medication was 80% (24 of 30) in group 1, with eUUN ratio <=-25%;
      82.2% (111 of 135) in group 2, with eUUN ratio between -25% and 25%; and 66.1%
      (37 and 56) in group 3, with eUUN ratio >=25% (P = 0.048). The probability of a
      decrease in albuminuria with ARB treatment was lower in patients with an increase
      of eUUN or protein intake during the 16 wk of ARB treatment, as observed in
      multiple logistic regression analysis as well. CONCLUSIONS: The estimated urine
      urea excretion rate showed a positive association with the level of albuminuria
      in hypertensive patients with chronic kidney disease. The increase of eUUN
      excretion ameliorated the antiproteinuric effect of ARB.

PMID- 26304597
TI  - The Breast Implant Rupture Warranty: What Is It Really Worth?

PMID- 26304596
TI  - Functional Identification of a Novel Gene, moaE, for 3-Succinoylpyridine
      Degradation in Pseudomonas putida S16.
AB  - Microbial degradation of N-heterocyclic compounds, including xanthine, quinoline,
      nicotinate, and nicotine, frequently requires molybdenum hydroxylases. The
      intramolecular electron transfer chain of molybdenum hydroxylases consists of a
      molybdenum cofactor, two distinct [2Fe-2S] clusters, and flavin adenine
      dinucleotide. 3-Succinoylpyridine monooxygenase (Spm), responsible for the
      transformation from 3-succinoylpyridine to 6-hydroxy-3-succinoylpyridine, is a
      crucial enzyme in the pyrrolidine pathway of nicotine degradation in Pseudomonas.
      Our previous work revealed that the heterotrimeric enzyme (SpmA, SpmB, and SpmC)
      requires molybdopterin cytosine dinucleotide as a cofactor for their activities.
      In this study, we knocked out four genes, including PPS_1556, PPS_2936, PPS_4063,
      and PPS_4397, and found that a novel gene, PPS_4397 encoding moaE, is necessary
      for molybdopterin cytosine dinucleotide biosynthesis. Resting cell reactions of
      the moaE deletion mutant incubated with 3 g l(-1) nicotine at 30  degrees C
      resulted in accumulation of 3-succinoylpyridine, and the strain complemented by
      the moaE gene regained the ability to convert 3-succinoylpyridine. In addition,
      reverse transcription-quantitative polymerase chain reaction analysis indicated
      that the transcriptional levels of the genes of moaE, spmA, and spmC of
      Pseudomonas putida S16 were distinctly higher when grown in nicotine medium than
      in glycerol medium. 

PMID- 26304598
TI  - Comparative Assessment of the Cleft Profile by Patients with Cleft Lip and
      Palate, Cleft Surgeons, and Lay People.
AB  - BACKGROUND: This cross-sectional study aimed to compare subjective assessments
      among patients with cleft lip and palate (CLP), cleft surgeons, and lay people
      regarding the soft tissue lateral profile of CLP patients. We also investigated
      the correlations between subjective assessments and photogrammetric measurements.
      METHODS: A total of 150 CLP patients who wished to have treatment for their
      unattractive appearance were randomly selected. A standard lateral profile color
      photograph was taken. Panels of three cleft surgeons, ten CLP patients, and ten
      lay people were selected to be assessors. They rated nasal tip projection,
      nasolabial esthetics, upper and lower lip esthetics, and the profile for each
      photograph. Three angular measurements (nasal prominence angle, nasolabial angle,
      and lip angle) were measured for each photograph. Kendall's coefficient of
      concordance and logistic regression were used for statistical analysis. RESULTS:
      Kendall's coefficient of concordance of nasal tip projection, nasolabial
      esthetics, upper and lower lip esthetics, and the profile were 0.734, 0.683,
      0.828, and 0.747, respectively (p < 0.001). Lip angle was associated with the
      profile scores for cleft surgeons and CLP patients (p < 0.001). The nasal
      prominence angle and lip angle were associated with the profile scores for lay
      people (p < 0.001). CONCLUSIONS: CLP patients, cleft surgeons, and lay people
      have similar attitudes to the appearance of CLP patients. Upper and lower lip
      esthetics is associated with the assessment of the cleft profile that is provided
      by CLP patients, cleft surgeons, and lay people. In addition, nasal tip
      projection is another determining factor for lay people. 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- 26304599
TI  - The In Vivo Pericapsular Tissue Response to Modern Polyurethane Breast Implants.
AB  - Polyurethane breast implants were first introduced by Ashley (Plast Reconstr Surg
      45:421-424, 1970), with the intention of trying to reduce the high incidence of
      capsular contracture associated with smooth shelled, high gel bleed, silicone
      breast implants. The sterilization of the polyurethane foam in the early days was
      questionable. More recently, ethylene oxide (ETO)-sterilized polyurethane has
      been used in the manufacturing process and this has been shown to reduce the
      incidence of biofilm. The improved method of attachment of polyurethane onto the
      underlying high cohesive gel, barrier shell layered, silicone breast implants
      also encourages bio-integration. Polyurethane covered, cohesive gel, silicone
      implants have also been shown to reduce the incidence of other problems commonly
      associated with smooth or textured silicone implants, especially with reference
      to displacement, capsular contracture, seroma, reoperation, biofilm and implant
      rupture. Since the introduction of the conical polyurethane implant (Silimed,
      Brazil) into the United Kingdom in 2009 (Eurosurgical, UK), we have had the
      opportunity to review histology taken from the capsules of polyurethane implants
      in three women ranging from a few months to over 3 years after implantation. All
      implants had been inserted into virgin subfascial, extra-pectoral planes. The
      results add to the important previously described histological findings of
      Bassetto et al. (Aesthet Plast Surg 34:481-485, 2010). Five distinct layers are
      identified and reasons for the development of each layer are discussed. Breast
      capsule around polyurethane implants, in situ for fifteen and 20 years, has
      recently been obtained and analysed in Brazil, and the histology has been
      incorporated into this study. After 20 years, the polyurethane is almost
      undetectable and capsular contracture may appear. These findings contribute to
      our understanding of polyurethane implant safety, and give reasoning for a
      significant reduction in clinical capsular contracture rate, up to 10 years after
      implantation, compared to contemporary silicone implants. A more permanent matrix
      equivalent to polyurethane may be the solution for reducing long-term capsular
      contracture. LEVEL OF EVIDENCE V: This journal requires that authors assign a
      level of evidence to each article. For a full description of these Evidence-Based
      Medicine ratings, please refer to the Table of Contents or the online
      Instructions to Authors www.springer.com/00266 .

PMID- 26304600
TI  - Energy Expenditure After Liver Resection: Validation of a Mobile Device for
      Estimating Resting Energy Expenditure and an Investigation of Energy Expenditure
      Change After Liver Resection.
AB  - BACKGROUND: Resting energy expenditure (REE) is the major component of total
      energy expenditure. REE is traditionally performed by indirect calorimetry (IC)
      and is not well investigated after liver surgery. A mobile device (SenseWear
      Armband [SWA]) has been validated when estimating REE in other clinical settings
      but not liver resection. The aims of this study are to validate SWA vs IC,
      quantify REE change following liver resection, and determine factors associated
      with REE change. MATERIALS AND METHODS: Patients listed for open liver resection
      prospectively underwent IC and SWA REE recordings pre- and postoperatively. In
      addition, the SWA was worn continuously postoperatively to estimate daily REE for
      the first 5 postoperative days. To determine acceptability of the SWA, validation
      analysis was performed. To assess REE change, peak postoperative REE was compared
      with preoperative levels. Factors associated with REE change were also analyzed.
      RESULTS: SWA showed satisfactory validity compared with IC when estimating REE,
      although postoperatively, the 95% levels of agreement (-5.56 to 3.18 kcal/kg/d)
      may introduce error. Postoperative REE (median, 23.5 kcal/kg/d; interquartile
      range [IQR], 22.6-25.7 kcal/kg/d) was significantly higher than predicted REE
      (median, 19.7 kcal/kg/d; IQR, 19.1-21.0 kcal/kg/d; P < .0001). Median REE rise
      was 11% (IQR, -1% to 25%). Factors associated with REE rise of >11% were age ( P
      = .017) and length of operation ( P = .03). CONCLUSIONS: SWA offers a suitable
      alternative to IC when estimating postoperative REE, but the magnitude of the
      error (8.74 kcal/kg/d) could hinder its accuracy. REE quantification after liver
      resection is important to identify patients who could be prone to energy
      imbalance and therefore malnutrition.

PMID- 26304601
TI  - Teduglutide-Stimulated Intestinal Adaptation Is Complemented and Synergistically
      Enhanced by Partial Enteral Nutrition in a Neonatal Piglet Model of Short Bowel
      Syndrome.
AB  - BACKGROUND: Teduglutide, a glucagon-like peptide-2 (GLP-2) analogue, is available
      for long-term use by parenteral nutrition (PN)-dependent adults to promote
      intestinal adaptation but is not approved for use in pediatric patients. The
      objective of this study was to assess teduglutide-stimulated induced intestinal
      adaptation, potential synergies with partial enteral nutrition (PEN), and
      distinct temporal markers of adaptation in a neonatal piglet model of short bowel
      syndrome (SBS). MATERIALS AND METHODS: Neonatal piglets (48 hours old; n = 72)
      underwent an 80% jejunoileal resection and were randomized to 1 of 4 treatment
      groups, in a 2 * 2 factorial design, with PN or PEN (80% standard PN/20% standard
      enteral nutrition) and teduglutide (0.1 mg/kg/d) or control. Piglets received
      nutrient infusions for 4 hours, 48 hours, or 7 days. RESULTS: Teduglutide
      improved ( P < .05) mucosal surface area (villus height: duodenum, jejunum,
      ileum; crypt depth: ileum, colon; proliferation: duodenum, jejunum, ileum; colon;
      apoptosis: jejunum, ileum, colon) and acute nutrient processing capacity
      (glucose: duodenum, jejunum, ileum; glutamine: duodenum, jejunum). These effects
      were complemented and synergistically enhanced by PEN in both site and timing of
      action. Structural adaptations preceded functional adaptations, but crypt depth
      remained a strong indicator of adaptation, regardless of time. CONCLUSIONS: The
      combination of teduglutide and PEN enhances intestinal adaptation beyond that of
      either therapy alone.

PMID- 26304602
TI  - Evaluation of an Intravenous Potassium Dosing Algorithm for Hypokalemic
      Critically Ill Patients.
AB  - PURPOSE: The intent of this study was to evaluate the safety and efficacy of an
      intravenous (IV) potassium (K) dosing algorithm for hypokalemic critically ill
      trauma patients. METHODS: Adult patients, admitted to the trauma intensive care
      unit from June 2010 to October 2012 and who received IV K therapy according to a
      standardized dosing algorithm, were retrospectively evaluated. Patients who
      received IV K during resuscitation or following initiation of nutrition therapy,
      IV fluids containing >20 mEq/L of potassium, or medications known to alter K
      homeostasis or those with an arterial pH change >0.1, diarrhea, hypomagnesemia,
      renal impairment, or morbid obesity were excluded. RESULTS: In total, 715
      patients were reviewed to obtain 100 evaluable patients. Serum K for patients
      with mild depletion (serum K, 3.5-3.9 mEq/L, n = 74) remained unchanged at 0.0 +/
      0.3 mEq/L ( P = ns) following 46 +/- 8 mEq. Serum K increased by 0.4 +/- 0.3
      mEq/L ( P = .001) following 78 +/- 18 mEq during moderate depletion (serum K, 3
      3.4 mEq/L). None of the patients experienced hyperkalemia (serum K, >5.2 mEq/L)
      postinfusion. The presence of traumatic brain injury (TBI) blunted the response
      to IV K for mild K depletion as only 26% had an increase in serum K compared with
      55% of patients without TBI ( P = .025). CONCLUSIONS: The Nutrition Support
      Service-guided IV K dosing algorithm was safe for patients with mild and moderate
      hypokalemia and efficacious for those with moderate hypokalemia. Further study in
      patients with severe hypokalemia (serum K, <3 mEq/L) is warranted.

PMID- 26304603
TI  - Condylar reconstruction in the treatment of temporomandibular joint ankylosis: a
      contribution to the ongoing debate and a plea to join forces for tissue
      engineering strategies.

PMID- 26304604
TI  - Administration of teriparatide improves the symptoms of advanced bisphosphonate
      related osteonecrosis of the jaw: preliminary findings.
AB  - Teriparatide is a synthetic polypeptide hormone that contains the 1-34 amino acid
      fragment of the recombinant human parathyroid hormone that stimulates bone
      formation. Currently, it is approved only for the treatment of osteoporosis. The
      outcomes of daily teriparatide injections for the treatment of bisphosphonate
      related osteonecrosis of the jaw in 10 patients are reported here. Two of the 10
      cases dropped out due to adverse events. Of the remaining eight cases, seven
      exhibited clinical improvement of the jaw-related symptoms of osteonecrosis and
      progression of the sequestration, while one case did not show improvement of the
      symptoms. Administration of teriparatide in patients with osteonecrosis of the
      jaw promotes bone formation and subsequent sequestration over a short period of
      time. These results suggest that adjunctive teriparatide therapy is a viable and
      effective option for treating osteonecrosis of the jaw. 

PMID- 26304605
TI  - Social anxiety in orthognathic patients.
AB  - There is evidence that patients seeking orthognathic treatment may be motivated
      by social anxiety disorder (SAD). The aim of this study was to investigate SAD in
      orthognathic patients using the Brief Fear of Negative Evaluation Scale (BFNES)
      and to compare these findings with those of the general population. This was a
      cross-sectional, questionnaire study conducted in two parts. Firstly, a national
      survey was conducted to yield data for the BFNES from a large, random sample of
      the UK general population. Secondly, orthognathic patients completed the BFNES.
      The BFNES scores are reported in two formats: the original 12-item scale (O
      BFNES) and a shorter eight-item version (S-BFNES). With regards to the national
      survey, 1196 individuals participated. The mean O-BFNES score was 29.72 (standard
      deviation (SD) 9.39) and S-BFNES score was 15.59 (SD 7.67). With regards to the
      orthognathic sample, 61 patients participated. The mean O-BFNES score was 39.56
      (SD 10.35) and the mean S-BFNES score was 24.21 (SD 8.41). Orthognathic patients
      had significantly higher scores than the general UK population (P<0.001), and
      multiple linear regression revealed that age, gender, and patient status were all
      independent predictors of BFNES scores. From the results of this study,
      orthognathic patients experience significantly higher levels of social anxiety
      than the general population. 

PMID- 26304606
TI  - Localized Tail States and Electron Mobility in Amorphous ZnON Thin Film
      Transistors.
AB  - The density of localized tail states in amorphous ZnON (a-ZnON) thin film
      transistors (TFTs) is deduced from the measured current-voltage characteristics.
      The extracted values of tail state density at the conduction band minima (N(tc))
      and its characteristic energy (kT(t)) are about 2 * 10(20) cm(-3)eV(-1) and 29
      meV, respectively, suggesting trap-limited conduction prevails at room
      temperature. Based on trap-limited conduction theory where these tail state
      parameters are considered, electron mobility is accurately retrieved using a self
      consistent extraction method along with the scaling factor '1/(alpha + 1)'
      associated with trapping events at the localized tail states. Additionally, it is
      found that defects, e.g. oxygen and/or nitrogen vacancies, can be ionized under
      illumination with hv ? E(g), leading to very mild persistent photoconductivity
      (PPC) in a-ZnON TFTs.

PMID- 26304607
TI  - Prognostic Impact of Distribution of Lymph Node Metastases in Stage III Colon
      Cancer.
AB  - BACKGROUND: Complete mesocolic excision (CME) with central vascular ligation
      (CVL) is a well-known concept in colon cancer surgery. However, data on the
      oncological benefits of CVL are scarce. The objective of this study was to
      evaluate the prognostic significance of the distribution of lymph node metastases
      (LND) in patients with stage III colon cancer who underwent CME with CVL.
      METHODS: In total, 446 consecutive patients who underwent curative resection for
      stage III colon cancer from 2005 to 2011 were analyzed. Patients were classified
      as having LND1 (metastases in pericolic nodes), LND2 (metastases in intermediate
      nodes), or LND3 (metastases in main nodes). Survival outcomes were compared among
      the three groups. RESULTS: LND1, LND2, and LND3 were identified in 299 (67.0 %),
      122 (27.4 %), and 25 (5.6 %) patients, respectively. The 5-year overall survival
      and relapse-free survival (RFS) of all patients were 86.7 and 76.2 %,
      respectively. The 5-year RFS of patients with LND1, LND2, and LND3 were 82.8,
      65.4, and 52.0 %, respectively (p < 0.0001). Multivariate analysis showed that
      LND2 was an independent prognostic factor for RFS (p = 0.0185), although the
      significance of LND3 was marginal (p = 0.0621). Among patients with pN1, the 5
      year RFS of patients with LND1 and LND2+3 were significantly different (84.4 vs.
      71.5 %, respectively, p = 0.0102), and similar tendency was found between
      patients with pN2-LND1 and pN2-LND2+3 (72.6 vs. 53.1 %, p = 0.0428). CONCLUSION:
      The high 5-year survival rates of patients with stage III colon cancer, even
      those with LND2 and LND3, would justify CVL as the standard procedure for
      advanced colon cancer.

PMID- 26304609
TI  - The Clinical Impact of 6-Min Walk Test Distance as a Predictor of Complications
      in Patients Undergoing Major Surgery.

PMID- 26304608
TI  - Preoperative Sequential Portal and Hepatic Vein Embolization in Patients with
      Hepatobiliary Malignancy.
AB  - BACKGROUND: Preoperative portal vein embolization (PVE) induces shrinkage of the
      embolized lobe and compensatory regeneration in the non-embolized lobe, but does
      not always induce sufficient regeneration of the future remnant liver (FRL). We
      previously developed preoperative sequential PVE-hepatic vein embolization (HVE),
      and here we present our experience of treating 42 patients with sequential PVE
      HVE. METHODS: During 8-year study period, preoperative PVE-HVE was performed on
      42 patients with hepatobiliary malignancies. RESULTS: Primary diseases were bile
      duct cancers [perihilar cholangiocarcinoma (n = 33) and diffuse bile duct cancer
      (n = 1)], hepatocellular carcinomas (n = 4), and intrahepatic tumors
      [intrahepatic cholangiocarcinoma (n = 3) and gallbladder cancer liver invasion (n
      = 1)]. These patients demonstrated insufficient FRL regeneration following PVE,
      thus HVE was performed to induce further regeneration. No PVE-HVE procedure
      associated complications occurred. In the bile duct cancer group, FRL volume was
      33.9 +/- 2.2 % before PVE, 38.4 +/- 1.5 % before HVE, 43.7 +/- 2.1 % at surgery,
      and 73.6 +/- 8.3 % at 2 weeks after right hepatectomy. The degree of FRL
      hypertrophy was 13.3 % after PVE, 28.9 % after PHV-HVE, and 117.1 % at 2 weeks
      after right hepatectomy. All patients except one recovered uneventfully after
      surgery, and the 3-year patient survival rate was 45.1 %. In the HCC group,
      transarterial chemoembolization was initially performed and FRL regeneration
      following PVE-HVE occurred very slowly. Active FRL regeneration occurred in the
      liver tumor group, but rapid tumor growth was observed in 1 of 4 patients.
      CONCLUSION: The sequential application of HVE following PVE safely and
      effectively induces further FRL regeneration in non-cirrhotic livers. Further
      validation using larger patient population and multicenter studies is needed to
      reliably widen the indications.

PMID- 26304610
TI  - Emergency Abdominal Operations in the Elderly: A Multivariate Regression Analysis
      of 430 Consecutive Patients with Acute Abdomen.
AB  - BACKGROUND: This study is intended to ascertain if outcome of acute abdominal
      surgery among elderly patients with acute abdominal pain have improved. METHODS:
      Altogether 456 patients aged >65 years underwent emergency abdominal surgery
      between the years 2007 and 2009 in our hospital. After excluding emergency
      reoperations of elective surgery, a total of 430 consecutive patients were
      included in this retrospective audit. The key factors under analysis in this
      study were the occurrence of major complications and death from any cause within
      30 days after the operation. In addition, we compared our results to our
      previously published data some 20 years ago. RESULTS: The most common diagnoses
      were cholecystitis (n = 139, 32.3 %, incidence of 125 per 100,000 elderly
      persons), incarcerated hernia (n = 60, 13.9 %, 54/100,000), malignancy related (n
      = 50, 11.6 %, 45/100,000), or acute appendicitis (n = 46, 10.7 %, 41/100,000).
      The majority of operations (80.7 %) were performed using open technique. Of all
      112 laparoscopic procedures, 25.9 % were converted to open surgery. Reoperations
      were rare and postoperative surgical complications were not associated with
      statistically significant increase in mortality, even if reoperation was needed.
      The 30-day mortality and morbidity rates were 14.2 and 31.9 %, respectively.
      Logistic regression analysis showed that patient's age (p = 0.014), atrial
      fibrillation (p = 0.017), low body mass index (p = 0.001), open surgery (p =
      0.029), ASA grade III or more (p < 0.001), and previous history of malignancies
      (p = 0.010) were likely to increase mortality. CONCLUSIONS: Despite modern
      diagnostics and improved surgical techniques, the results of emergency abdominal
      surgery still have relatively high morbidity and mortality as reported in earlier
      studies.

PMID- 26304611
TI  - Wound Disruption Following Colorectal Operations.
AB  - OBJECTIVES: Postoperative wound disruption is associated with high morbidity and
      mortality. We sought to identify the risk factors and outcomes of wound
      disruption following colorectal resection. METHODS: The American College of
      Surgeons National Surgical Quality Improvement Program (NSQIP) database was used
      to examine the clinical data of patients who underwent colorectal resection from
      2005 to 2013. Multivariate regression analysis was performed to identify risk
      factors of wound disruption. RESULTS: We sampled a total of 164,297 patients who
      underwent colorectal resection. Of these, 2073 (1.3 %) had wound disruption.
      Patients with wound disruption had significantly higher mortality (5.1 vs. 1.9 %,
      AOR: 1.46, P = 0.01). The highest risk of wound disruption was seen in patients
      with wound infection (4.8 vs. 0.9 %, AOR: 4.11, P < 0.01). A number of factors
      are associated with wound disruption such as chronic steroid use (AOR: 1.71, P <
      0.01), smoking (AOR: 1.60, P < 0.01), obesity (AOR: 1.57, P < 0.01), operation
      length more than 3 h (AOR: 1.56, P < 0.01), severe Chronic Obstructive Pulmonary
      Disease (COPD) (AOR: 1.36, P < 0.01), urgent/emergent admission (AOR: 1.31, P =
      0.01), and serum Albumin Level <3 g/dL (AOR: 1.27, P < 0.01). Laparoscopic
      surgery had significantly lower risk of wound disruption compared to open surgery
      (AOR: 0.61, P < 0.01). CONCLUSION: Wound disruption occurs in 1.3 % of colorectal
      resections, and it correlates with mortality of patients. Wound infection is the
      strongest predictor of wound disruption. Chronic steroid use, obesity, severe
      COPD, prolonged operation, non-elective admission, and serum albumin level are
      strongly associated with wound disruption. Utilization of the laparoscopic
      approach may decrease the risk of wound disruption when possible.

PMID- 26304613
TI  - Changing the Culture of Cholecystectomy.

PMID- 26304612
TI  - Pathologic Assessment of Pancreatic Fibrosis for Objective Prediction of
      Pancreatic Fistula and Management of Prophylactic Drain Removal After
      Pancreaticoduodenectomy.
AB  - BACKGROUND: Soft pancreatic texture is a commonly accepted risk factor associated
      with pancreatic fistula (PF) after pancreaticoduodenectomy (PD). However, its
      evaluation is subjective and its predictive value is limited. The present study
      was performed to establish intraoperative PF prediction parameter: the
      pathological assessment of pancreatic fibrosis, which was an objective evaluation
      that was strongly related to pancreatic consistency. METHODS: Based on the
      results of a retrospective investigation on grades of pancreatic fibrosis and PF
      occurrence in 51 consecutive patients, an algorithm for intraoperative selection
      of early prophylactic drain removal was established. Prophylactic drains of
      patients with pancreatic fibrosis >= 30 % in the frozen section of pancreatic
      stump were removed on postoperative day (POD) 4. As CRP >= 10 mg/dL on POD 4 was
      a strong risk factor for PF in patients with fibrosis <30 %, the drains of these
      patients were maintained. RESULTS: The algorithm was applied to 26 consecutive
      patients. Prophylactic drains were removed in 14 patients and retained in 12
      patients on POD 4. No PF was observed in patients with pancreatic fibrosis >= 30
      % (n = 8). Among six patients with fibrosis <30 %, CRP <10 mg/dL, and without
      infection in the drain fluid, only two developed grade A PF. All nine patients
      with pancreatic fibrosis <30 % and CRP >= 10 mg/dL developed grade B PF. No grade
      C PF was observed in any group. CONCLUSIONS: The pathological evaluation of
      pancreatic fibrosis could objectively predict PF occurrence. Intraoperative
      assessment of pancreatic fibrosis could be applied to tailor postoperative drain
      management after PD.

PMID- 26304614
TI  - Splenic Arterial Embolization in the Treatment of Severe Portal Hypertension Due
      to Pancreatic Diseases: The Primary Experience in 14 Patients.
AB  - OBJECTIVE: This retrospective study reports our experience using splenic arterial
      particle embolization and coil embolization for the treatment of sinistral portal
      hypertension (SPH) in patients with and without gastric bleeding. METHODS: From
      August 2009 to May 2012, 14 patients with SPH due to pancreatic disease were
      diagnosed and treated with splenic arterial embolization. Two different
      embolization strategies were applied; either combined distal splenic bed particle
      embolization and proximal splenic artery coil embolization in the same procedure
      for acute hemorrhage (1-step) or interval staged distal embolization and proximal
      embolization in the stable patient (2-step). The patients were clinically
      followed. RESULTS: In 14 patients, splenic arterial embolization was successful.
      The one-step method was performed in three patients suffering from massive
      gastric bleeding, and the bleeding was relieved after embolization. The two-step
      method was used in 11 patients, who had chronic gastric variceal bleeding or
      gastric varices only. The gastric varices disappeared in the enhanced CT scan and
      the patients had no gastric bleeding during follow-up. CONCLUSIONS: Splenic
      arterial embolization, particularly the two-step method, proved feasible and
      effective for the treatment of SPH patients with gastric varices or gastric
      variceal bleeding.

PMID- 26304615
TI  - A detailed evaluation of cardiac function in cirrhotic patients and its
      alteration with or without liver transplantation.
AB  - BACKGROUND: Cirrhosis has been shown to be associated with left ventricular (LV)
      myocardial dysfunction, but studies of right ventricular (RV) function in
      cirrhotic patients compared with controls are scarce. Limited studies have
      prospectively evaluated the progression of myocardial function in patients with
      cirrhosis and assessed changes in cardiac function following liver
      transplantation (LTx). So the aim of the study was to evaluate biventricular
      myocardial function in cirrhotic patients and its alteration with or without
      liver transplantation. METHODS: A total of 103 patients with cirrhosis (age 55+/
      7 years, male 75%) were recruited. Conventional and 2-dimensional speckle
      tracking echocardiography was performed to determine the presence of LV and RV
      (biventricular) dysfunction. For comparison, 48 matched control subjects were
      included. Follow-up echocardiography was performed in 41 patients following LTx
      and in 26 patients who did not undergo LTx. RESULTS: Patients with cirrhosis had
      biventricular dilatation, increased LV mass, impaired LV diastolic function, and
      biventricular systolic strain compared with controls. Following LTx, cirrhotic
      patients had reduced biventricular dilatation, a smaller LV mass, and improved
      biventricular systolic strain after a mean duration of 18.2+/-6.6 months.
      Patients who did not undergo LTx had a further increase in LV mass but no
      significant change in biventricular dimensions or systolic strain (mean duration
      of 20.4+/-8.3 months). CONCLUSIONS: The present study demonstrates that patients
      with cirrhosis had biventricular dilatation and impaired biventricular systolic
      strain compared with controls. Following LTx, biventricular dilatation reduced
      and biventricular systolic strain improved. In contrast, patients who did not
      undergo LTx experienced a further increase in LV mass.

PMID- 26304616
TI  - Scale invariance analysis for genetic networks applying homogeneity.
AB  - Scalability is a property describing the change of the trajectory of a dynamical
      system under a scaling of the input stimulus and of the initial conditions.
      Particular cases of scalability include the scale invariance and fold change
      detection (when the scaling of the input does not influence the system output).
      In the present paper it is shown that homogeneous systems have this scalability
      property while locally homogeneous systems approximately possess this property.
      These facts are used for detecting scale invariance or approximate scalability
      (far from a steady state) in several biological systems. The results are
      illustrated by various regulatory networks. 

PMID- 26304617
TI  - A model for collective dynamics in ant raids.
AB  - Ant raiding, the process of identifying and returning food to the nest or
      bivouac, is a fascinating example of collective motion in nature. During such
      raids ants lay pheromones to form trails for others to find a food source. In
      this work a coupled PDE/ODE model is introduced to study ant dynamics and
      pheromone concentration. The key idea is the introduction of two forms of ant
      dynamics: foraging and returning, each governed by different environmental and
      social cues. The model accounts for all aspects of the raiding cycle including
      local collisional interactions, the laying of pheromone along a trail, and the
      transition from one class of ants to another. Through analysis of an order
      parameter measuring the orientational order in the system, the model shows self
      organization into a collective state consisting of lanes of ants moving in
      opposite directions as well as the transition back to the individual state once
      the food source is depleted matching prior experimental results. This indicates
      that in the absence of direct communication ants naturally form an efficient
      method for transporting food to the nest/bivouac. The model exhibits a continuous
      kinetic phase transition in the order parameter as a function of certain system
      parameters. The associated critical exponents are found, shedding light on the
      behavior of the system near the transition. 

PMID- 26304618
TI  - Glycoprotein Ia C807T: Polymorphisms and Their Association with Platelet Function
      in Patients with the Acute Coronary Syndrome.
AB  - OBJECTIVES: In the current study, we explored the relationship between
      glycoprotein Ia (GPIa) C807T polymorphisms and platelet function, and the
      sensitivity to dual antiplatelet treatment after percutaneous coronary
      intervention. MATERIALS AND METHODS: We conducted a case-control study in 220
      patients diagnosed with acute coronary syndrome (ACS) and 220 healthy controls.
      The platelet GPIa C807T genotypes of patients and controls were determined, and
      platelet aggregation and plasma concentrations of alpha-granule membrane protein
      (GMP-140) were assessed following stimulation with arachidonic acid and adenosine
      diphosphate. RESULTS: The frequency of the GPIa T allele was higher in the ACS
      group than in controls. In the ACS group, platelet aggregation was significantly
      higher in individuals with the T allele than in those with the C allele. Dual
      antiplatelet treatment reduced platelet aggregation in all three genotypes, and
      patients carrying the CC genotype were more sensitive to antiplatelet treatment
      than those with the T allele, particularly the ones with the TT genotype. There
      were no differences in plasma GMP-140 levels. CONCLUSIONS: The GPIa C807T
      polymorphism might be a risk factor for the development and relapse of ACS. The
      GP Ia T allele may help to identify a group of patients who need more aggressive
      antithrombotic treatment.

PMID- 26304619
TI  - New Self-Expanding Transcatheter Valve for Off-Pump Transatrial Mitral Valve-In
      Ring Implantation.
AB  - OBJECTIVES: To validate a self-expanding transcatheter valve for off-pump
      transatrial mitral valve-in-ring (VIR) implantation via a left thoracotomy.
      METHODS: Mitral valve annuloplasty was performed via sternotomy during
      cardiopulmonary bypass on 9 pigs. After successful weaning from extracorporal
      circulation, the custom-made, self-expanding transcatheter VIR device was
      deployed under fluoroscopic guidance within the annuloplasty ring via a left
      thoracotomy. Hemodynamic data before and after the implantation were recorded.
      Mitral annulus diameter and valve area were measured by echocardiography.
      Transvalvular and left-ventricular outflow-tract pressure gradient were measured
      invasively. RESULTS: Eight successful implantations were performed. Implantation
      failed in 1 pig because of difficulty with technical delivery of the sheath. Mean
      transatrial procedure time was 12.6 +/- 1.7 min. Hemodynamic status during
      transatrial implantation was stable, and differences were not statistically
      significant. Mean mitral annulus diameter and mean mitral orifice area were 2.32
      +/- 0.2 and 3.84 +/- 0.55 cm2, respectively. Mild regurgitation was detected in 7
      animals and moderate regurgitation in 1. Mean gradients were 6.1 +/- 5.0 mm Hg
      across the device. Postmortem examination confirmed adequate positioning of
      devices within the annuloplasty ring. CONCLUSIONS: This custom-made transcatheter
      device allows for safe and reproducible off-pump transatrial mitral VIR
      implantations. Transatrial access is a promising route to facilitate VIR
      implantations. Our custom-made stent-valve may be suitable for VIR procedures.

PMID- 26304620
TI  - Novel Clinical Manifestation of the Known SCN5A D1790G Mutation.
AB  - The D1790G mutation was found in all 24 patients of an extended long QT family
      but not in 200 chromosomes carried by healthy individuals. We describe a 37-year
      old man presenting with a typical spontaneous type 1 Brugada pattern who in
      electrophysiological testing had easily inducible ventricular fibrillation. At
      the age of 47 years he had an atrial ventricular type 2 block documented by an
      exercise test and a Holter monitor. Genetic analysis revealed a known D1790G
      mutation in the gene encoding of the sodium channel (SCN5A) that until now has
      been associated only with the long QT phenotype. Although this mutation has not
      been associated with a reduction of sodium channel expression, we hypothesize
      that sodium currents are further diminished due to the 20-mV shift of the steady
      state inactivation curve, and this could contribute to the Brugada phenotype.
      This case is important as it allows a better understanding of the underlying
      molecular mechanisms of Brugada syndrome. Moreover, this observation raises
      concern about the safety of class IC drug therapy in long QT type 3 patients and
      quinidine therapy in Brugada patients, and emphasizes the importance of a
      thorough clinical and genetic evaluation. 

PMID- 26304621
TI  - mHealth: An updated systematic review with a focus on HIV/AIDS and tuberculosis
      long term management using mobile phones.
AB  - OBJECTIVE: To evaluate the utilization of mobile phone technology for treatment
      adherence, prevention, education, data collection, monitoring long-term
      management of HIV/AIDS and TB patients. METHODS: Articles published in English
      language from January 2005 until now from PubMed/MEDLINE, EMBASE, Web of Science,
      WHO databases, and clinical trials were included. Data extraction is based on
      medication adherence, quality of care, prevention, education, motivation for HIV
      test, data collection from HIV lab test results and patient monitoring. Articles
      selected for the analysis cover RCTs and non RCTs related to the use of mobile
      phones for long-term care and treatment of HIV/AIDS and TB patients. RESULTS: Out
      of 90 articles selected for the analysis, a large number of studies, 44 (49%)
      were conducted in developing countries, 24 (26%) studies from developed
      countries, 12 (13%) are systematic reviews and 10 (11%) did not mention study
      location. Forty seven (52.2%) articles focused on treatment, 11 (12.2%) on
      quality of care, 8 (9%) on prevention, 13 (14.4%) on education, 6 (6.6%) on data
      collection, and 5 (5.5%) on patient monitoring. Overall, 66 (73%) articles
      reported positive effects, 21 (23%) were neutral and 3 (4%) reported negative
      results. CONCLUSIONS: Mobile phone technology is widely reported to be an
      effective tool for HIV/AIDS and TB long-term care. It can substantially reduce
      disease burden on health care systems by rendering more efficient prevention,
      treatment, education, data collection and management support.

PMID- 26304622
TI  - Optofluidic laser array based on stable high-Q Fabry-Perot microcavities.
AB  - We report the development of an optofluidic laser array fabricated on a chip
      using stable plano-concave Fabry-Perot (FP) microcavities, which are far less
      susceptible to optical misalignment during device assembly than the commonly used
      plano-plano FP microcavities. The concave mirrors in our FP microcavities were
      created by first generating an array of microwells of a few micrometers in depth
      and a few tens of micrometers in diameter on a fused silica chip using a CO2
      laser, followed by coating of distributed Bragg reflection (DBR) layers. The
      plano-concave FP microcavity had a Q-factor of 5.6 * 10(5) and finesse of 4 *
      10(3), over 100 times higher than those for the FP microcavities in existing
      optofluidic lasers. 1 mM R6G dye in ethanol was used to test the plano-concave FP
      microcavities, showing an ultralow lasing threshold of only 90 nJ mm(-2), over 10
      times lower than that in the corresponding unstable plano-plano FP microcavities
      formed by the same DBR coatings on the same chip. Simultaneous laser emission
      from the optofluidic laser array on the chip and single-mode lasing operation
      were also demonstrated. Our work will lead to the development of optofluidic
      laser-based biochemical sensors and novel on-chip photonic devices with extremely
      low lasing thresholds (nJ mm(-2)) and mode volumes (fL). 

PMID- 26304624
TI  - Investigation for Ebola virus environmental contamination in an Ebola virus
      disease convalescent ward.

PMID- 26304625
TI  - Mother's Perception of General Family Functioning and Sugar Consumption of 3- and
      4-Year-Old Children: The East London Family Study.
AB  - Frequent consumption of sugary foods is a common risk factor for chronic diseases
      such as dental caries and obesity. Dietary patterns are acquired at home during
      early life and form a blueprint for dietary behaviours in later life. A
      favourable family environment can provide a supportive context that enhances the
      adoption of healthy dietary habits. The aim of this study was to identify the
      contribution of general family functioning towards the frequent consumption of
      sugary foods by 3- and 4-year-old children in Outer North East London. The
      research question was explored with data from the East London Family study, which
      collected data through home visits from a representative sample of adults and
      children living in Outer North East London in 2008-2010. This study analysed data
      from 3- and 4-year-old children (n = 698) and their mothers and included logistic
      regression, conceptual hierarchical modelling and mediation analysis. The results
      showed that 17% of the sample consumed sugary foods more than 4 times per day,
      and that effective general family functioning may help reducing frequent
      consumption of sugary foods. There was a 67% reduction in children's frequent
      consumption of sugary foods with every unit increase in the general family
      functioning score. Mother's higher education may also help reduce the frequent
      consumption of sugary foods by children. The negative impact of mother's lower
      education was buffered by the effect of effective general family functioning. The
      study findings underscore the prospect of identifying factors that contribute to
      the acquisition of good dietary behaviours. 

PMID- 26304626
TI  - Patient falls in hospitals: an increasing problem.
AB  - Despite six decades of worldwide efforts that include publishing virtually
      hundreds of related epidemiological-type studies, there has been an increase
      (estimated to be 46% per 1000 patient days from 1954-6 to 2006-10) in the number
      of patient falls in hospitals and other health care facilities. These still occur
      most frequently near the bedside or in the bathroom, among mentally confused or
      physically impaired patients, and often involve those with greater comorbidity.
      The reasons that hospitals during the past half century have demonstrated a
      significant increase in patient falls per discharge or per patient days are
      numerous, are not completely surprising, and are certainly interrelated: improved
      accident reporting systems; on the average older, more impaired, more acutely
      ill, and more heavily sedated patients; and, less time spent by nursing personnel
      at the bedside. Most safety committees are not as effective as they should be,
      since they have difficulty in implementing a long-term, aggressive, facility-wide
      prevention program. Within that context, it may be worthwhile to discuss the
      advantages of nursing leadership rather than a representative of the facility's
      management staff to chair these safety committees.

PMID- 26304627
TI  - Medicare screening vulnerabilities--caution for providers.

PMID- 26304629
TI  - Cognitive Functions Buffer Age Differences in Technology Ownership.
AB  - BACKGROUND: Technology plays a major role in enhancing quality of life and
      everyday competence in old age. Mechanic and pragmatic cognitive functions are
      known to serve as resources when using technology in everyday life. Not much is
      known about the differential role of mechanic and pragmatic cognitive functions
      when moderating reduced technology ownership in old age. OBJECTIVE: In this
      research, we explored whether perceptual speed or verbal fluency is more
      important for buffering age differences in technology ownership. We investigate
      possible moderation effects of cognitive functions relative to demographic
      characteristics, socioeconomic status, and household composition variables.
      METHODS: We report findings based on a nationally representative German sample of
      3,357 younger and older adults between 18 and 94 years of age (mean = 51.2, SD =
      17.3). Interaction and relative importance analyses were conducted to examine the
      relative importance of perceptual speed and verbal fluency for the moderation of
      age differences in technology ownership across adulthood. RESULTS: Findings
      suggest that perceptual speed (B = 0.0008, t = 6.23, p < 0.001) and verbal
      fluency (B = 0.0003, t = 2.70, p < 0.01) buffered age differences in technology
      ownership. The moderating role of perceptual speed remained robust (B = 0.0007, t
      = 5.48, p < 0.001) when including interactions of age with demographic,
      socioeconomic, and household composition variables; however, the interaction
      between age and verbal fluency was no longer significant (B = 0.0002, t = 1.82, p
      = 0.069). Relative importance analysis indicates that perceptual speed was the
      most important moderator of age differences (DW = 0.0121), whereas verbal fluency
      was less important for moderating the relation between age and technology
      ownership (DW = 0.0039). CONCLUSIONS: Mechanic and pragmatic cognitive functions
      may serve differently as moderators of the relation between age and technology
      ownership. Our findings suggest that perceptual speed was more important for
      buffering age differences in technology ownership than verbal fluency. Such
      findings underscore the relevance of information processing for the ownership of
      technological devices in late life.

PMID- 26304628
TI  - Simvastatin impairs the induction of pulmonary fibrosis caused by a western style
      diet: a preliminary study.
AB  - The role of an atherogenic diet in causing pulmonary fibrosis has received little
      attention and simvastatin has been shown to reduce pulmonary fibrosis in animal
      models. To determine if an atherogenic diet can induce pulmonary fibrosis and
      whether simvastatin treatment is beneficial by up-regulating heat shock protein
      70 and 90. New Zealand white rabbits (n = 15) were divided: Group 1 (control);
      Group 2 (MC) received a normal rabbit diet with 1% methionine plus 0.5%
      cholesterol (atherogenic diet). Group 3 received the same diet as the MC group
      plus 5 mg/kg/day simvastatin orally (MCS). After 4 weeks, the lungs were
      collected and analysed. Picrosirus red staining of lung interstitial collagen
      content showed that the atherogenic diet increased fibrosis 2.9-fold (P < 0.05),
      bronchiole adventitial collagen was increased 2.3-fold (P < 0.05) and bronchiole
      epithelium was increased 34-fold (P < 0.05), and simvastatin treatment severely
      reduced this effect (P < 0.05). Western blot analysis showed that the atherogenic
      diet significantly reduced lung Hsp70 protein by 22% (P < 0.05) and Hsp90 protein
      by 18% (P < 0.05) and simvastatin treatment did not affect this result. However,
      aortic hyper-responsiveness to vasoconstrictors (angiotensin II and
      phenylephrine) were markedly reduced by simvastatin treatment. We report that an
      atherogenic diet stimulates pulmonary fibrosis and reduces lung Hsp70/Hsp90
      protein concentration. Simvastatin impairs this by mechanisms unrelated to
      Hsp70/Hsp90, but possibly a reduction in angiotensin II receptor or alpha
      adrenergic receptor pathways. These results could have implications in idiopathic
      pulmonary fibrosis.

PMID- 26304630
TI  - AJMQ newsletter: the new third science in medical education-medical quality.

PMID- 26304631
TI  - Replication analysis of genetic variants on 17q11.2 and 9p21.2 with sporadic
      amyotrophic lateral sclerosis and Parkinson's disease in a Chinese population.
AB  - We performed a replication study of the 2 genetic variants, rs34517613 on 17q11.2
      and rs3849942 on 9p21.2 in patients with sporadic amyotrophic lateral sclerosis
      (ALS) and Parkinson's disease in a Chinese population. These 2 variants are
      identified to be associated with increased risk of ALS in European-descended
      populations by genome-wide association studies. Both rs34517613 and rs3849942
      showed no evidence of association in Chinese. These loci are not risk factors for
      sporadic ALS and Parkinson's disease in the western Han Chinese population. 

PMID- 26304632
TI  - Association Study of GWAS-Derived Loci with Height in Brazilian Children:
      Importance of MAP3K3, MMP24 and IGF1R Polymorphisms for Height Variation.
AB  - BACKGROUND/AIM: The single nucleotide polymorphisms (SNPs) rs2282978 (CDK6),
      rs2425019 (MMP24), rs8081612 (MAP3K3), rs2871865 (IGF1R) and rs3782415 (SOCS2)
      were among the SNPs most strongly associated with height in a meta-analysis of 47
      genome-wide association studies (GWAS) involving 114,223 adults from six ethnic
      groups. The present study aimed to examine associations between these SNPs and
      height in Brazilian children. METHODS: Cross-sectional heights of 1,008 healthy
      unrelated 4.4- to 9.7-year-old children were evaluated. All genotypes were
      determined by allele-specific polymerase chain reactions. Height standard
      deviation scores (SDS) were generated for this population and regressed on allele
      counts. Linear regressions were performed to estimate the effect of individual
      SNPs or a polygenic allelic score on height. RESULTS: The T allele of rs8081612
      (MAP3K3), the C allele of rs2871865 (IGF1R) and the G allele of rs2425019 (MMP24)
      were significantly associated with a 0.091-SDS greater height (95% CI 0.089
      0.093, p = 0.001) by polygenic analysis. The mean height SDS difference between
      children with 2 'tall' alleles and children with 4 'tall' alleles was 0.24 SDS
      (95% CI 0.05-0.43, p = 0.01). The observed allelic effect is consistent with that
      found in previous GWAS. CONCLUSIONS: Polymorphisms in MAP3K3, MMP24 and IGF1R act
      additively on height in children of an admixed population. These results
      demonstrate the importance of these loci for children's height.

PMID- 26304633
TI  - Burden of Care and Patient's Neuropsychiatric Symptoms Influence Carer's
      Evaluation of Cognitive Impairment.
AB  - OBJECTIVES: The aim of this study was to explore what effects the carer's burden
      and patient's neuropsychiatric symptoms have on carer's report on patient's
      cognitive functioning and instrumental activities of daily living (IADL).
      METHODS: We included 1,832 patients, 742 with mild cognitive impairment and 1,090
      with dementia [mean age 75.2 years (SD 9.5), 56% women]. The following scales
      were used: Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE),
      Lawton and Brody IADL Scale, Neuropsychiatric Inventory Questionnaire (NPI-Q),
      Relatives' Stress Scale (RSS), Mini-Mental State Examination (MMSE), and Clock
      Drawing Test (CDT). Correlation analyses and multiple linear regression analyses
      were carried out to explore which factors were associated with IQCODE and IADL.
      RESULTS: Spouses scored lower on the IQCODE compared with non-spouses in spite of
      equivalent MMSE and CDT scores. In a multiple linear regression analysis using
      IQCODE as a dependent variable, beta for MMSE was -0.368 (p < 0.001) adjusted for
      demographic factors. After adjusting also for RSS and NPI-Q, MMSE beta was -0.279
      (p < 0.001), RSS beta 0.294 (p < 0.001), and NPI beta 0.237 (p < 0.001). Similar
      results were found using IADL as the dependent variable. CONCLUSION: Carer's
      burden and neuropsychiatric symptoms of the patient are important biasing factors
      when carers report on cognitive function and IADL.

PMID- 26304634
TI  - [Experience with a new self-expanding metal stent specifically designed for wound
      dehiscence after sleeve gastrectomy].

PMID- 26304635
TI  - Changes in Visual Acuity after Idiopathic Epiretinal Membrane Removal: Good
      versus Poor Preoperative Visual Acuity.
AB  - PURPOSE: To investigate postoperative visual acuity changes following idiopathic
      epiretinal membrane (ERM) surgery as well as investigate the relationship between
      outcome and baseline visual acuity. METHODS: The medical records of 159
      consecutive eyes were retrospectively reviewed for best corrected visual acuity
      (BCVA), central subfield macular thickness (CSMT), and the ellipsoid zone (EZ)
      signal of the photoreceptor layer at baseline and 1, 3, and 6 months after
      surgery. Patients were divided into two groups: group A, with good vision of
      20/50 or better, and group B, with poor visual acuity worse than 20/50. RESULTS:
      Seventy-nine eyes were included in group A and 80 eyes in group B. Mean baseline
      BCVA was 0.28 and 0.65 logarithm of the minimum angle of resolution (logMAR), and
      the mean baseline CSMT was 423.7 and 505.6 MUm in group A and group B,
      respectively. In group A, BCVA worsened to 0.39 logMAR at 1 month (p < 0.001) and
      gradually improved to 0.25 logMAR at 6 months, which was not different from
      baseline BCVA. In group B, BCVA and CSMT improved at 1, 3, and 6 months (p <
      0.05). The EZ signal improved in group B (p = 0.003) but not in group A. The area
      under the receiver operating characteristic curve for the improvement in BCVA of
      >= 2 lines was significant for preoperative BCVA (0.717, 95% confidence interval
      0.638-0.797; p < 0.001). The cutoff value was 0.35 on the logMAR scale.
      CONCLUSION: After ERM surgery, patients with good vision maintained visual acuity
      after temporary worsening of vision, and patients with poor vision achieved
      significant BCVA improvement.

PMID- 26304636
TI  - [Improving shared decision-making for hospital patients: Description and
      evaluation of a treatment intensity assessment tool].
AB  - BACKGROUND AND AIM: Shared decision-making between patients and healthcare
      professionals is crucial to guarantee adequate coherence between patient values
      and preferences, caring aims and treatment intensity, which is key for the
      provision of patient-centred healthcare. The assessment of such interventions are
      essential for caring continuity purposes. To do this, reliable and easy-to-use
      assessment systems are required. This study describes the results of the
      implementation of a hospital treatment intensity assessment tool. MATERIAL AND
      METHODS: The pre-implementation and post-implementation results were compared
      between two cohorts of patients assessed for one month. RESULTS: Some record of
      care was registered in 6.1% of patients in the pre-implementation group (n=673)
      compared to 31.6% of patients in the post-implementation group (n=832) (P<.01),
      with differences between services. Hospital mortality in both cohorts is 1.9%; in
      the pre-implementation group, 93.75% of deceased patients had treatment intensity
      assessment. CONCLUSIONS: In hospital settings, the availability of a specific
      tool seems to encourage very significantly shared decision-making processes
      between patients and healthcare professionals -multiplying by more than 5 times
      the treatment intensity assessment. Moreover, such tools help in the caring
      continuity processes between different teams and the personalisation of caring
      interventions to be monitored. More research is needed to continue improving
      shared decision-making for hospital patients.

PMID- 26304637
TI  - Excursion of the Sciatic Nerve During Nerve Mobilization Exercises: An In Vivo
      Cross-sectional Study Using Dynamic Ultrasound Imaging.
AB  - STUDY DESIGN: Controlled laboratory cross-sectional study using single-group,
      within-subject comparisons. OBJECTIVES: To determine whether different types of
      neurodynamic techniques result in differences in longitudinal sciatic nerve
      excursion. BACKGROUND: Large differences in nerve biomechanics have been
      demonstrated for different neurodynamic techniques for the upper limb (median
      nerve), but recent findings for the sciatic nerve have only revealed small
      differences in nerve excursion that may not be clinically meaningful. METHODS:
      High-resolution ultrasound imaging was used to quantify longitudinal sciatic
      nerve movement in the thigh of 15 asymptomatic participants during 6 different
      mobilization techniques for the sciatic nerve involving the hip and knee. Healthy
      volunteers were selected to demonstrate normal nerve biomechanics and to
      eliminate potentially confounding variables associated with dysfunction. Repeated
      measures analyses of variance were used to analyze the data. RESULTS: The
      techniques resulted in markedly different amounts of nerve movement (P<.001). The
      tensioning technique was associated with the smallest excursion (mean +/- SD, 3.2
      +/- 2.1 mm; P < or = .004). The sliding technique resulted in the largest
      excursion (mean +/- SD, 17.0 +/- 5.2 mm; P<.001), which was approximately 5 times
      larger than that resulting from the tensioning technique and, on average, twice
      as large as that resulting from individual hip or knee movements. CONCLUSION:
      Consistent with current theories and findings for the median nerve, different
      neurodynamic exercises for the lower limb resulted in markedly different sciatic
      nerve excursions. Considering the continuity of the nervous system, the movement
      and position of adjacent joints have a large impact on nerve biomechanics.

PMID- 26304638
TI  - Predicting Dynamic Foot Function From Static Foot Posture: Comparison Between
      Visual Assessment, Motion Analysis, and a Commercially Available Depth Camera.
AB  - STUDY DESIGN :Controlled laboratory study. OBJECTIVE: To evaluate the ability of
      3 methods to assess static foot posture to predict rearfoot and midfoot
      kinematics during gait. BACKGROUND: Static foot posture is commonly used
      clinically to infer dynamic function. Limitations of static clinical assessments
      may be overcome through advances in technologies, including commercially
      available depth cameras. METHODS: The Foot Posture Index (FPI) of 31 males
      (average age, 22.5 years) was assessed using visual observation, a 3-D motion
      analysis system, and a depth camera. Pearson correlations were used to evaluate
      relationships between FPI items and rearfoot and midfoot kinematics during
      walking. The ability of the static variables to predict dynamic function was
      assessed using multiple linear regression. RESULTS: Most FPI items (85%) were not
      correlated with foot kinematics, regardless of assessment method. There were 6
      fair to moderate correlations between visual FPI items and total rearfoot (r = 
      0.36 to -0.39, P<.05) and midfoot (r = 0.37 to 0.61, P<.05) motion, 2 fair
      correlations between 3-D motion-analysis FPI items and total midfoot (r = -0.43,
      P = .02) and peak rearfoot (r = -0.40, P = .03) motion, and 2 fair correlations
      between the depth-camera FPI items and average rearfoot (r = -0.38 to 0.44,
      P<.05) motion. Visual assessment of the FPI provided the best prediction model,
      explaining 37% of the variance in total midfoot inversion/eversion. CONCLUSION:
      Static measures of foot posture are weakly correlated with rearfoot or midfoot
      kinematics, and have limited dynamic prediction ability. Our findings suggest
      that the FPI may not be an accurate representation of rearfoot or midfoot
      movement during walking, regardless of the measurement technique employed.

PMID- 26304639
TI  - The Immediate Effects on Inter-rectus Distance of Abdominal Crunch and Drawing-in
      Exercises During Pregnancy and the Postpartum Period.
AB  - STUDY DESIGN: Longitudinal descriptive exploratory study. OBJECTIVES: To evaluate
      in primigravid women the immediate effect of drawing-in and abdominal crunch
      exercises on inter-rectus distance (IRD), measured at 4 time points during
      pregnancy and in the postpartum period. BACKGROUND: There is scant knowledge of
      the effect of different abdominal exercises on IRD in pregnant and postpartum
      women. METHODS: The study included 84 primiparous participants. Ultrasound images
      were recorded with a 12-MHz linear transducer, at rest and during abdominal
      drawing-in and abdominal crunch exercises, at 3 locations on the linea alba. The
      IRD was measured at 4 time points: gestational weeks 35 to 41, 6 to 8 weeks
      postpartum, 12 to 14 weeks postpartum, and 24 to 26 weeks postpartum. Separate 2
      way, repeated-measures analyses of variance (ANOVAs) were performed for each
      exercise (drawing-in and abdominal crunch) and each measurement location to
      evaluate the immediate effects of exercises on IRD at each of the 4 time points.
      Similarly, 2-way ANOVAs were used to contrast the effects of the 2 exercises on
      IRD. RESULTS: Performing the drawing-in exercise caused a significant change in
      width of the IRD at 2 cm below the umbilicus, narrowing the IRD by a mean of 3.8
      mm (95% confidence interval [CI]: 1.2, 6.4 mm) at gestational weeks 35 to 41, and
      widening the IRD by 3.0 mm (95% CI: 1.4, 4.6 mm) at 6 to 8 weeks postpartum, by
      1.8 mm (95% CI: 0.6, 3.1 mm) at 12 to 14 weeks postpartum, and by 2.5 mm (95% CI:
      1.4, 3.6 mm) at 24 to 26 weeks postpartum (P<.01). Performing the abdominal
      crunch exercise led to a significant narrowing of the IRD (P<.01) in all 3
      locations at all 4 time points, with the exception of 2 cm below the umbilicus at
      postpartum weeks 24 to 26. The average amount of narrowing varied from 1.6 to
      20.9 mm, based on time and location. CONCLUSION: Overall, there was a contrasting
      effect of the 2 exercises, with the abdominal crunch exercise consistently
      producing a significant narrowing of the IRD. In contrast, the drawing-in
      exercise generally led to a small widening of the IRD.

PMID- 26304640
TI  - Kinematic and Kinetic Analysis of the Single-Leg Triple Hop Test in Women With
      and Without Patellofemoral Pain.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVES: To compare the biomechanical
      strategies of the trunk and lower extremity during the transition period between
      the first and second hop of a single-leg triple hop test in women with and
      without patellofemoral pain (PFP). BACKGROUND: Recent literature has shown that
      PFP is associated with biomechanical impairments of the lower extremities. A
      number of studies have analyzed the position of the trunk and lower extremities
      for functional activities such as walking, squatting, jumping, and the step-down
      test. However, studies on more challenging activities, such as the single-leg
      triple hop test, may be more representative of sports requiring jumping
      movements. METHODS: Women between 18 and 35 years of age (control group, n = 20;
      PFP group, n = 20) participated in the study. Three-dimensional kinematic and
      kinetic data were collected during the transition period between the first and
      second hops while participants performed the single-leg triple hop test. RESULTS:
      Compared to the control group, women with PFP exhibited greater (P<.05) anterior
      and ipsilateral trunk lean, contralateral pelvic drop, hip internal rotation and
      adduction, and ankle eversion, while exhibiting less hip and knee flexion. A
      significant difference (P<.05) in time to peak joint angle was also found between
      groups for all the variables analyzed, except anterior pelvic tilt and hip
      flexion. In addition, women with PFP exhibited greater (P<.05) hip and knee
      abductor internal moments. CONCLUSION: Compared to the control group, women with
      PFP exhibited altered trunk, pelvis, hip, knee, and ankle kinematics and
      kinetics.

PMID- 26304641
TI  - Prevalence and re-infection rate of C. trachomatis genital infections in young
      people under 25 years in Catalonia.
AB  - INTRODUCTION: Chlamydia trachomatis infection is the most common bacterial
      sexually transmitted disease. Re-infections are a major problem in its control as
      they increase the probability of developing sequellae. OBJECTIVES: To estimate
      the prevalence of C.trachomatis and re-infection rate after 6 months of treatment
      by determining the possible causes. METHODS: Cross-sectional study in which a
      urine sample was analysed by PCR in a convenience sample of 506 sexually active
      youths aged 16-25years. An epidemiological survey and re-test was performed at
      3months. RESULTS: The prevalence of C.trachomatis was 8.5%. The age (OR=2.34;
      95%CI: 1.21-4.55) and concurrency (OR=3.64; 95% CI: 3.58-26.39) were determining
      factors for acquiring C.trachomatis. The re-infection rate was 10.34%.
      DISCUSSION: The high prevalence of C.trachomatis, as well as the rate of
      reinfection, suggest the need to assess the effectiveness of the opportunistic
      screening program and ensure high levels of reporting of sexual partners.
      Ensuring these approaches facilitate the control of C.trachomatis among young
      people.

PMID- 26304642
TI  - The Consequence of a Medial Ankle Sprain on Physical and Self-reported Functional
      Limitations: A Case Study Over a 5-Month Period.
AB  - STUDY DESIGN: Case report. BACKGROUND: Little evidence exists about impairments
      and perceived disability following eversion injury to the deltoid ligament. This
      case study prospectively examined the neuromuscular, biomechanical, and
      psychological consequences of a case of a medial ankle sprain. CASE DESCRIPTION:
      A recreationally active man with a history of a lateral ankle sprain (grade I)
      was participating in a university Institutional Review Board-approved research
      study examining the neuromuscular and mechanical characteristics associated with
      chronic ankle instability. Twenty-two days after the testing session, the
      participant sustained an eversion injury to his left ankle while playing
      basketball. Outcomes The outcomes of this case are presented using the
      International Classification of Functioning, Disability and Health model. Outcome
      variables were assessed at preinjury (medial ankle sprain), 3 months postinjury,
      and 5 months postinjury. Measurements included neural excitability of the soleus,
      balance assessment, joint stability, and psychological assessments. Data from
      this case study revealed that a medial ankle sprain reduces joint mobility and
      alters neural excitability of the soleus, with concurrent deficits in balance and
      self-reported function. These impairments forced the participant to downgrade his
      physical activity lifestyle up to 5 months postinjury. DISCUSSION: These data
      suggest the need for the development of intervention strategies to address
      impairments in neural excitability and joint mobility at the ankle to help
      patients meet the goal of maintaining long-term joint health. LEVEL OF EVIDENCE:
      Prognosis, level 4.

PMID- 26304643
TI  - Star Excursion Balance Test Performance Varies by Sport in Healthy Division I
      Collegiate Athletes.
AB  - STUDY DESIGN: Cross-sectional. OBJECTIVES: To describe performance and asymmetry
      on the Star Excursion Balance Test (SEBT) by sex and sport, and to determine if
      differences exist within a collegiate athlete population. BACKGROUND: Performance
      on the SEBT may differ between sexes and levels of competition, though the
      results of previous studies have been inconsistent. Investigation of performance
      and asymmetry differences between sports is limited. Sex- and sport-specific
      reference values likely need to be determined to best assess SEBT performance.
      METHODS: Performance on the SEBT was retrospectively reviewed in 393 healthy
      National Collegiate Athletic Association Division I collegiate athletes from 8
      sports. Means, standard deviations, and 95% confidence intervals were calculated
      for all variables. Normalized reach distance (percent limb length) and asymmetry
      between limbs were compared for the anterior (ANT), posterolateral (PL), and
      posteromedial (PM) directions and for the composite (COMP) score using a 2-way
      analysis of variance (ANOVA) of sex by sport, and a 1-way ANOVA to separately
      compare sports within each sex. RESULTS: Average normalized reach distance ranged
      from 62% to 69%, 84% to 97%, and 99% to 113% in the ANT, PL, and PM directions,
      respectively, and from 82% to 92% in the COMP score. Normalized asymmetry ranged
      from 3% to 4%, 5% to 8%, and 5% to 6% in the ANT, PL, and PM directions,
      respectively. A significant sex-by-sport interaction (P = .039) was observed in
      the ANT direction, with a sex effect for soccer players (P<.001; men less than
      women). Significant differences were observed in the PL and PM directions and in
      the COMP score among women's teams, with women's ice hockey players reaching the
      farthest (COMP, 90.0%). Among men's teams, significant differences were observed
      in all directions and in the COMP score. Men's ice hockey players (COMP, 91.9%)
      and wrestlers achieved the farthest distances (COMP, 88.8%). CONCLUSION:
      Performance on the SEBT varies by team, with a difference between sexes also
      present for soccer. Performance on the SEBT and potential injury risk should be
      interpreted within the context of the athlete's sport.

PMID- 26304644
TI  - Biomechanical Differences of Foot-Strike Patterns During Running: A Systematic
      Review With Meta-analysis.
AB  - STUDY DESIGN: Systematic review with meta-analysis. OBJECTIVES: To determine the
      biomechanical differences between foot-strike patterns used when running.
      BACKGROUND: Strike patterns during running have received attention in the recent
      literature due to their potential mechanical differences and associated injury
      risks. METHODS: Electronic databases (MEDLINE, Embase, LILACS, SciELO, and
      SPORTDiscus) were searched through July 2014. Studies (cross-sectional, case
      control, prospective, and retrospective) comparing the biomechanical
      characteristics of foot-strike patterns during running in distance runners at
      least 18 years of age were included in this review. Two independent reviewers
      evaluated the risk of bias. A meta-analysis with a random-effects model was used
      to combine the data from the included studies. RESULTS: Sixteen studies were
      included in the final analysis. In the meta-analyses of kinematic variables,
      significant differences between forefoot and rearfoot strikers were found for
      foot and knee angle at initial contact and knee flexion range of motion. A
      forefoot-strike pattern resulted in a plantar-flexed ankle position and a more
      flexed knee position, compared to a dorsiflexed ankle position and a more
      extended knee position for the rearfoot strikers, at initial contact with the
      ground. In the comparison of rearfoot and midfoot strikers, midfoot strikers
      demonstrated greater ankle dorsiflexion range of motion and decreased knee
      flexion range of motion compared to rearfoot strikers. For kinetic variables, the
      meta-analysis revealed that rearfoot strikers had higher vertical loading rates
      compared to forefoot strikers. CONCLUSION: There are differences in kinematic and
      kinetic characteristics between foot-strike patterns when running. Clinicians
      should be aware of these characteristics to help in the management of running
      injuries and advice on training.

PMID- 26304645
TI  - Validity of Inter-rectus Distance Measurement in Postpartum Women Using Extended
      Field-of-View Ultrasound Imaging Techniques.
AB  - STUDY DESIGN: Reliability and validity study. OBJECTIVES: To investigate the
      criterion-related validity and reliability of inter-rectus distance (IRD)
      measurement using extended field-of-view (FOV) techniques during ultrasound
      imaging (USI) in parous women. BACKGROUND: Ultrasound imaging is the gold
      standard for noninvasive IRD measurement in parous women when investigating
      diastasis recti; however, its use is limited when IRD is large. Extended FOV
      techniques (panoramic USI or using acoustic standoff pads) allow complete
      visualization of the linea alba when the IRD is large and conventional imaging is
      not sufficient; however, the validity of using these techniques has never been
      investigated. METHODS: Two-dimensional ultrasound images were acquired at the
      superior umbilical border from 21 women using conventional USI, panoramic USI,
      and a standoff pad. Five images were captured using each method. Inter-rectus
      distance was measured offline. Criterion-related validity was investigated using
      repeated-measures analyses of variance to test for bias, and linear regression
      models, Pearson correlation coefficients (r), and intraclass correlation
      coefficients (ICCs) to assess agreement. Standard error of the measurement for
      each extended FOV technique was calculated. The between-trial reliability of each
      technique was determined using ICCs. RESULTS: Inter-rectus distance from images
      acquired using extended FOV techniques did not differ from values acquired using
      conventional USI (P = .441). Images acquired using extended FOV techniques were
      highly correlated with those acquired using conventional imaging (r>0.95,
      P<.0001). The standard error of the measurement of each extended FOV technique
      was 0.17 to 0.18 cm. The between-trial reliability of all techniques was
      excellent (ICC(3,1)>0.90). CONCLUSION: Panoramic USI and acoustic standoff pads
      are valid methods of increasing FOV to measure IRD. In this study, USI
      measurements were limited to IRDs of less than or equal to 3 finger widths, based
      on palpation.

PMID- 26304647
TI  - Unilateral retrobulbar optic neuropathy as the initial manifestation of human
      immunodeficiency virus infection.

PMID- 26304646
TI  - Knee Confidence as It Relates to Self-reported and Objective Correlates of Knee
      Osteoarthritis: A Cross-sectional Study of 220 Patients.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVE: The objective was to validate, if
      possible, previously reported associations and to investigate other potential
      associations between knee confidence and various self-reported and objective
      measures in an independent cohort of patients with knee osteoarthritis (OA).
      BACKGROUND: Lack of knee confidence is a frequent symptom in patients with knee
      OA, but little is known of associations between knee confidence and other common
      correlates of knee OA. METHODS: Baseline data from 220 patients with knee OA were
      applied in ordinal regression analyses, with knee confidence, assessed using item
      Q3 of the Knee injury and Osteoarthritis Outcome Score, as the dependent variable
      and self-reported (pain on walking, general health, fear of movement, self
      efficacy, function, and previous serious injury) and objective measures (muscle
      strength, 20-m walk time, and radiographic severity of tibiofemoral OA) as
      predictor variables. RESULTS: Most (95%) of the participants reported lack of
      knee confidence, and 54% experienced severe or extreme lack of knee confidence.
      Fear of movement (odds ratio [OR] = 2.06; 95% confidence interval [CI]: 1.15,
      3.68), pain on walking (OR = 1.21; 95% CI: 1.09, 1.34), and general health (OR =
      0.024; 95% CI: 0.002, 0.259) explained 19% of the variance in knee confidence
      (P<.001). CONCLUSION: Severe lack of knee confidence is a common finding in
      individuals with knee OA. Pain on walking was confirmed as a correlate of knee
      confidence, whereas muscle strength was not. Fear of movement and poor general
      health were new variables associated with lack of knee confidence. The
      noncorrelations or poor correlations with other tested variables suggest that a
      lack of knee confidence may represent an independent treatment target in knee OA
      of importance to improve mobility. Trials registered at ClinicalTrials.gov
      (NCT01410409 and NCT01535001).

PMID- 26304648
TI  - 'Chronic migraine' is a misnomer.

PMID- 26304649
TI  - The "three-hour effect" constitutes procrastination in thrombolytic stroke
      treatment.

PMID- 26304650
TI  - The effect of manual therapy on tension headache.

PMID- 26304651
TI  - Molecular diagnosis in cerebral cavernous malformations.
AB  - INTRODUCTION: Cerebral cavernous malformations (CCMs; OMIM 116860) are enlarged
      vascular cavities without intervening brain parenchyma whose estimated prevalence
      in the general population is between 0.1% and 0.5%. Familial CCM is an autosomal
      dominant disease with incomplete clinical and radiological penetrance. Three
      genes have been linked to development of the lesions: CCM1/KRIT1, CCM2/MGC4607,
      and CCM3/PDCD10. DEVELOPMENT: The aetiological mutation is not detected in a
      large percentage of cases and new approaches are therefore needed. The aim of
      this review is to analyse current molecular techniques and the possible mutations
      or variations which can be detected in a molecular genetics or molecular biology
      laboratory. Likewise, we will analyse other alternatives that may help detect
      mutations in those patients showing negative results. CONCLUSIONS: A molecular
      diagnosis of cerebral cavernous malformations should provide at least the copy
      number variation and sequencing of CCM genes. In addition, appropriate genetic
      counselling is a crucial source of information and support for patients and their
      relatives.

PMID- 26304652
TI  - Sociodemographic characteristics of a cohort of patients with chronic migraine
      from a health district in Asturias.
AB  - INTRODUCTION: Chronic migraine (CM), with or without medication overuse, is a
      common condition in the general population. It has traditionally been assumed
      that suffering CM has an impact on a patient's socio-occupational and educational
      level. Our goal was to analyse these characteristics in a cohort of patients with
      CM and compare them to the general population. MATERIAL AND METHODS: We used a
      telephone interview and an ad hoc questionnaire to record and analyse the
      sociodemographic characteristics of 150 patients with a diagnosis of CM according
      to the criteria of the International Headache Classification. Results were
      compared to those obtained by the Third Health Survey of Asturias, conducted in
      2012. RESULTS: Of the 150 patients, 142 were women (95%). Married patients
      accounted for 59.3% of the total interviewees, while 22% were single, 12.6%
      divorced, and 6% were widowed. Regarding educational level, we found that 73% of
      our patients had completed secondary or higher education and 25% had completed
      only primary education. Sixty per cent of these patients are occupationally
      active, while the rest are not actively employed. Overall, these figures do not
      differ from those published by the Third Health Survey of Asturias. DISCUSSION:
      The classic idea that CM has a negative impact on patients' educational,
      personal, and occupational situations was not confirmed in our series. In fact,
      most patients with CM reported a medium-high educational level and a good socio
      occupational status. However, since our series includes only CM patients attended
      in a specialist clinic, our results are not necessarily applicable to all
      patients with CM.

PMID- 26304653
TI  - Evolution and genomics of the human brain.
AB  - Most living beings are able to perform actions that can be considered intelligent
      or, at the very least, the result of an appropriate reaction to changing
      circumstances in their environment. However, the intelligence or intellectual
      processes of humans are vastly superior to those achieved by all other species.
      The adult human brain is a highly complex organ weighing approximately 1500g,
      which accounts for only 2% of the total body weight but consumes an amount of
      energy equal to that required by all skeletal muscle at rest. Although the human
      brain displays a typical primate structure, it can be identified by its specific
      distinguishing features. The process of evolution and humanisation of the Homo
      sapiens brain resulted in a unique and distinct organ with the largest relative
      volume of any animal species. It also permitted structural reorganization of
      tissues and circuits in specific segments and regions. These steps explain the
      remarkable cognitive abilities of modern humans compared not only with other
      species in our genus, but also with older members of our own species. Brain
      evolution required the coexistence of two adaptation mechanisms. The first
      involves genetic changes that occur at the species level, and the second occurs
      at the individual level and involves changes in chromatin organisation or
      epigenetic changes. The genetic mechanisms include: a) genetic changes in coding
      regions that lead to changes in the sequence and activity of existing proteins;
      b) duplication and deletion of previously existing genes; c) changes in gene
      expression through changes in the regulatory sequences of different genes; and d)
      synthesis of non-coding RNAs. Lastly, this review describes some of the main
      documented chromosomal differences between humans and great apes. These
      differences have also contributed to the evolution and humanisation process of
      the H. sapiens brain.

PMID- 26304654
TI  - Alcock canal syndrome secondary to endometrial infiltration.

PMID- 26304655
TI  - The 6-hydroxydopamine model and parkinsonian pathophysiology: Novel findings in
      an older model.
AB  - The neurotoxin 6-hydroxydopamine (6-OHDA) is widely used to induce models of
      Parkinson's disease (PD). We now know that the model induced by 6-OHDA does not
      include all PD symptoms, although it does reproduce the main cellular processes
      involved in PD, such as oxidative stress, neurodegeneration, neuroinflammation,
      and neuronal death by apoptosis. In this review we analyse the factors affecting
      the vulnerability of dopaminergic neurons as well as the close relationships
      between neuroinflammation, neurodegeneration, and apoptosis in the 6-OHDA model.
      Knowledge of the mechanisms involved in neurodegeneration and cell death in this
      model is the key to identifying potential therapeutic targets for PD.

PMID- 26304656
TI  - Ethical considerations in presymptomatic diagnosis of autosomal dominant
      spinocerebellar ataxias.
AB  - INTRODUCTION: Information on achieving presymptomatic diagnosis of
      spinocerebellar ataxia (SCA) is limited. The advent of molecular diagnosis makes
      it possible to identify the carriers of different diseases and has also
      introduced the prospect of detecting diseases even before their onset. This has
      drawn attention to the ethical implications that must be considered in these
      subjects with a view to preserving their physical and psychological well-being.
      DEVELOPMENT: SCA is composed of a group of neurodegenerative disorders with
      autosomal dominant inheritance. Only a few publications have described the
      genetic counselling processes and guidelines to be followed during the process of
      presymptomatic diagnosis (PSD). The size of the multidisciplinary teams, their
      areas of expertise, and the number of counselling sessions are different for each
      of the studies analysed here. However, the basis of presymptomatic diagnosis
      originates in common guidelines to which members of our team have contributed
      recently. CONCLUSION: Presymptomatic diagnosis should be performed according to
      guidelines that safeguard the subjects' welfare. The diagnostic process is only
      recommended for patients over 18 years old with symptoms suggesting SCA, and a
      minimum risk of 50%. Genetic counselling programmes must be available in all
      centres that offer presymptomatic diagnosis of SCA.

PMID- 26304657
TI  - Mechanical thrombectomy during ischaemic stroke due to a calcified cerebral
      embolism.

PMID- 26304658
TI  - Test Your Memory is sensitive to cognitive change but lacks prospective validity.
AB  - OBJECTIVE: To determine the prospective validity of Test Your Memory (TYM) and
      its sensitivity to change in cognitive state. METHODS: This longitudinal
      prospective study followed 71 patients with subjective cognitive symptoms and 48
      with mild cognitive impairment for a mean time period of 35.2 +/- 15 months.
      Subjects did not have dementia or depression at the beginning of follow-up and
      each participant was given the TYM at least two times. A psychometric threshold
      was established to determine presence of a cognitive deficit (z-score <= 1.5 on
      at least one cognitive domain) and the Disability Assessment for Dementia scale
      was used to ensure full functional ability. The criterion for deterioration was a
      change in the stage on the Global Deterioration Scale. RESULTS: Sixty-one
      patients remained cognitively stable and 58 worsened. There were no differences
      between them with respect to sex, educational attainment, the initial stage on
      the GDS, or the score on the first TYM. Subjects who worsened were older than
      those who did not. The TYM increased an average of 0.04 points per month in
      patients who remained stable or improved (95% CI, -0.01 to 0.08) and decreased an
      average of 0.14 points per month in those whose condition worsened (95% CI, -0.19
      to -0.09). Subjects with mild cognitive impairment who worsened displayed a
      sharper loss of TYM points than did subjects with subjective cognitive symptoms.
      CONCLUSIONS: While the TYM lacks prospective validity, it is sensitive to changes
      in cognitive state.

PMID- 26304659
TI  - Drug utilisation study in patients receiving antiepileptic drugs in Colombia.
AB  - INTRODUCTION: This study examines the indications according to which
      antiepileptic drugs are prescribed and used in a population of patients enrolled
      in the Colombian national health system (SGSSS). METHODS: Retrospective cross
      sectional study. From the pool of individuals in 34 Colombian cities who used
      antiepileptic drugs between 18 July, 2013 and 31 August, 2014 during a period of
      no less than 12 months, we obtained a random sample stratified by city. Socio
      demographic, pharmacological and comorbidity variables were analysed. Continuous
      and categorical variables were compared, and logistic regression models were
      used. RESULTS: Our patient total was 373 patients, with 197 women (52.1%) and a
      mean age of 41.9 +/- 21.7 years; 65.4% of the patients were treated with
      monotherapy. The most frequently used drugs were valproic acid (53.1%) and
      carbamazepine (33.2%). Epilepsy was the most frequent indication (n=178; 47.7%);
      however, 52.3% of the patients were prescribed antiepileptics for different
      indications, especially neuropathic pain (26.8%), affective disorders (14.2%) and
      migraine prophylaxis (12.3%). A total of 81 patients with epilepsy (46.6%)
      displayed good seizure control while another 25 (14.4%) had drug-resistant
      epilepsy. In the multivariate analysis, medication adherence was associated with
      a lower risk of treatment failure in patients with epilepsy (OR: 0.27; 95%CI,
      0.11-0.67). CONCLUSIONS: In Colombia, antiepileptic drugs are being used for
      indications other than those originally intended. Monotherapy is the most
      commonly used treatment approach, together with the use of classic antiepileptic
      drugs.

PMID- 26304660
TI  - [Neurotoxic manifestations of black widow spider envenomation in paediatric
      patients].
AB  - INTRODUCTION: Envenomation by black widow spiders manifests clinically with signs
      of neurotoxicity in paediatric patients. OBJECTIVE: Identify typical neurological
      signs and symptoms in paediatric patients of different ages, and describe
      treatment and outcomes in a paediatric hospital in northwest Mexico. MATERIAL AND
      METHODS: We reviewed 70 clinical records of patients hospitalised due to black
      widow spider bite between 1978 and 2014. We divided the total into 2 groups:
      Group 1, infants and preschool children; and Group 2, school-age children and
      adolescents. The demographic variables were age, sex, birthplace, place where
      envenomation occurred, body part(s) affected, degree of envenomation according to
      signs and symptoms, treatment, clinical outcome, and statistical differences.
      RESULTS: Boys accounted for 61.4% of all cases, and infants younger than one year
      old made up 14.2%. Most patients (70%) were bitten by the spider at home; the
      anatomical areas most frequently affected were the legs, neck, thorax, and
      abdomen. The neurological signs and symptoms displayed by Group 1 were
      irritability, constant crying, sialorrhoea, nausea, tachycardia, arrhythmias,
      fatigue when walking, agitation, muscle spasms paraesthesia, tetany, seizures,
      and nystagmus. Signs in Group 2 included localized pain, headache, sialorrhoea,
      paraesthesia, profuse sweating, anxiety, muscle weakness, muscle spasms, and fine
      tremor. The predominant autonomic sign in Group 1 was sialorrhoea (P<.0001) and
      in Group 2, paraesthesia (P<.0001). Patients who received Fab antivenom treatment
      displayed better outcomes and shorter hospital stays than those who did not. No
      deaths were reported. CONCLUSIONS: The neurological signs and symptoms caused by
      black widow spider bite are predominantly autonomic, and identifying them permits
      early diagnosis and more effective treatment.

PMID- 26304662
TI  - Cardiovascular Surgery Supplement.

PMID- 26304661
TI  - Early-onset Alzheimer's disease versus frontotemporal dementia: resolution with
      genetic diagnoses?
AB  - We report a diagnostically challenging case of a 64-year-old man with a history
      of remote head trauma who developed mild behavioral changes and dyscalculia. He
      was diagnosed with clinical Alzheimer's disease (AD), with additional features
      consistent with behavioral variant frontotemporal dementia. Structural magnetic
      resonance imaging revealed atrophy in bilateral frontal and parietal cortices and
      hippocampi on visual inspection and left frontal pole and bilateral anterior
      temporal encephalomalacia, suspected to be due to head trauma. Consistent with
      the diagnosis of Alzheimer's pathology, positron emission tomography (PET) with
      Pittsburgh compound B suggested the presence of beta-amyloid. Fluorodeoxyglucose
      PET demonstrated hypometabolism in bilateral frontal and temporoparietal
      cortices. Voxel-based morphometry showed atrophy predominant in ventral frontal
      regions (bilateral orbitofrontal cortex, pregenual anterior cingulate/medial
      superior frontal gyrus), bilateral mid cingulate, bilateral lateral temporal
      cortex, and posterior insula. Bilateral caudate, thalamus, hippocampi, and
      cerebellum were prominently atrophied. Unexpectedly, a pathologic hexanucleotide
      repeat expansion in C9ORF72 was identified in this patient. This report
      underscores the clinical variability in C9ORF72 expansion carriers and the need
      to consider mixed pathologies, particularly when imaging studies are inconsistent
      with a single syndrome or pathology. 

PMID- 26304664
TI  - Does Timing of Coronary Artery Bypass Surgery Affect Early and Long-Term Outcomes
      in Patients With Non-ST-Segment-Elevation Myocardial Infarction?
AB  - BACKGROUND: Current guidelines do not provide recommendations for optimal timing
      of coronary artery bypass surgery (CABG) in patients with non-ST-segment
      elevation myocardial infarction. Our study aimed to determine the impact of CABG
      timing on early and late outcomes in patients with non-ST-segment-elevation
      myocardial infarction. METHODS AND RESULTS: A total of 758 patients underwent
      CABG within 21 days after non-ST-segment-elevation myocardial infarction between
      January 2008 and December 2012 at our institution. The patients were divided into
      3 groups according to the time interval between symptom onset and CABG: group A,
      <24 hours (133 patients); group B, 24 to 72 hours (192 patients); and group C,
      >72 hours to 21 days (433 patients). Predictors of in-hospital and long-term
      mortality were identified by logistic and Cox regression analyses, respectively.
      Overall in-hospital mortality was 5.1% (39 patients): 6.0%, 4.7%, and 5.1% in
      groups A, B, and C (P=0.9), respectively. A total of 118 patients died during
      follow-up. The 5-year survival was 73.1+/-2%, with a nonsignificant trend toward
      better survival in groups A (78.2+/-4%) and C (75.4+/-3%) compared with group B
      (63.6+/-5%; log-rank P=0.06). Renal insufficiency and LMD were independent
      predictors of in-hospital (odds ratio, 3.1; P=0.001; and odds ratio, 3.1;
      P=0.002) and long-term mortality (hazard ratio, 1.7; P=0.004; and hazard ratio,
      1.5; P=0.02), whereas administration of P2Y12 inhibitors was protective (odds
      ratio, 0.3; P=0.01). CONCLUSIONS: Emergent CABG within 24 hours of non-ST-segment
      elevation myocardial infarction is associated with in-hospital mortality and long
      term outcomes similar to those of CABG performed after 3 days, despite a higher
      risk profile. CABG performed between 24 to 72 hours showed a nonsignificant trend
      toward poorer long-term outcomes. Dual antiplatelet therapy until surgery is
      beneficial, whereas renal insufficiency and left main disease increase the risk
      of early and late death.

PMID- 26304663
TI  - Influence of Baseline Characteristics, Operative Conduct, and Postoperative
      Course on 30-Day Outcomes of Coronary Artery Bypass Grafting Among Patients With
      Left Ventricular Dysfunction: Results From the Surgical Treatment for Ischemic
      Heart Failure (STICH) Trial.
AB  - BACKGROUND: Patients with severe left ventricular dysfunction, ischemic heart
      failure, and coronary artery disease suitable for coronary artery bypass grafting
      (CABG) are at higher risk for surgical morbidity and mortality. Paradoxically,
      those patients with the most severe coronary artery disease and ventricular
      dysfunction who derive the greatest clinical benefit from CABG are also at the
      greatest operative risk, which makes decision making regarding whether to proceed
      to surgery difficult in such patients. To better inform such decision making, we
      analyzed the Surgical Treatment for Ischemic Heart Failure (STICH) CABG
      population for detailed information on perioperative risk and outcomes. METHODS
      AND RESULTS: In both STICH trials (hypotheses), 2136 patients with a left
      ventricular ejection fraction of <=35% and coronary artery disease were allocated
      to medical therapy, CABG plus medical therapy, or CABG with surgical ventricular
      reconstruction. Relationships of baseline characteristics and operative conduct
      with morbidity and mortality at 30 days were evaluated. There were a total of
      1460 patients randomized to and receiving surgery, and 346 (~25%) of these high
      risk patients developed a severe complication within 30 days. Worsening renal
      insufficiency, cardiac arrest with cardiopulmonary resuscitation, and ventricular
      arrhythmias were the most frequent complications and those most commonly
      associated with death. Mortality at 30 days was 5.1% and was generally preceded
      by a serious complication (65 of 74 deaths). Left ventricular size, renal
      dysfunction, advanced age, and atrial fibrillation/flutter were significant
      preoperative predictors of mortality within 30 days. Cardiopulmonary bypass time
      was the only independent surgical variable predictive of 30-day mortality.
      CONCLUSIONS: CABG can be performed with relatively low 30-day mortality in
      patients with left ventricular dysfunction. Serious postoperative complications
      occurred in nearly 1 in 4 patients and were associated with mortality. CLINICAL
      TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier:
      NCT00023595.

PMID- 26304665
TI  - Clinical Impact of Changes in Left Ventricular Function After Aortic Valve
      Replacement: Analysis From 3112 Patients.
AB  - BACKGROUND: Our objectives were to identify correlates of mortality and
      congestive heart failure after aortic valve replacement (AVR) according to
      preoperative left ventricular (LV) function and to describe the incidence, time
      course, and correlates of LV recovery and mass regression postoperatively.
      METHODS AND RESULTS: A total of 3112 patients with AVR were assessed in a follow
      up clinic with echocardiography (median follow-up, 6.0 years). At operation,
      their mean age was 67.8+/-13.4 years, one third were female, and 29% had LV
      dysfunction (ejection fraction <50%). In severe patients with severe aortic
      stenosis and LV dysfunction, transaortic valve mean pressure gradient <40 mm Hg,
      longer cardiopulmonary bypass duration, and prosthesis-patient mismatch (indexed
      effective orifice area <=0.85 cm(2)/m(2)) were independent correlates of the
      composite outcome of death or congestive heart failure after AVR. In patients
      with severe aortic regurgitation and LV dysfunction, older age and higher
      preoperative LV mass were identified. LV recovery correlated with better survival
      and freedom from heart failure in patients with aortic stenosis. Maximum LV mass
      regression took 24 months in patients with aortic stenosis and nearly 5 years
      with aortic regurgitation; independent correlates included smaller LV end
      systolic diameter in patients with aortic stenosis and low New York Heart
      Association class with aortic regurgitation. CONCLUSIONS: Incomplete LV recovery,
      prosthesis-patient mismatch, low transaortic valve pressure gradient, and higher
      LV mass are associated with increased mortality or heart failure after AVR in
      patients with LV dysfunction. Higher LV end-systolic diameter and symptoms
      correlate with less LV mass regression, which takes at least 2 years. These
      findings help surgeons and cardiologists refine the indications, timing,
      prognostication, and follow-up of patients before and after AVR.

PMID- 26304666
TI  - Outcomes of Patients With Acute Type B (DeBakey III) Aortic Dissection: A 13
      Year, Single-Center Experience.
AB  - BACKGROUND: Aortic dissection remains the most common aortic catastrophe. In the
      endovascular era, the management of acute type B aortic dissection (ATBAD) is
      undergoing dramatic changes. The aim of this study is to evaluate the long-term
      outcomes of patients with ATBAD who were treated at our center over a 13-year
      period. METHODS AND RESULTS: We reviewed patients with ATBAD between 2001 and
      2014, analyzing variables based on status (complicated [c] versus uncomplicated
      [u]) and treatment modalities. We defined cATBAD as rupture, expansion of
      diameter on imaging during the admission, persistent pain, or clinical
      malperfusion leading to a deficit in cerebral, spinal, visceral, renal, or
      peripheral vascular territories at presentation or during initial
      hospitalization. Postoperative outcomes were defined as deficits not present
      before the intervention. Outcomes were compared between the groups by use of
      Kaplan-Meier and descriptive statistics. We treated 442 patients with ATBAD. Of
      those 442, 60.6% had uATBAD and were treated medically, and 39.4% had cATBAD, of
      whom 39.0% were treated medically to 30.0% with open repair, 21.3% with thoracic
      endovascular aortic repair, and 9.7% with other open peripheral procedures.
      Intervention-free survival at 1 and 5 years was 84.8% and 62.7% for uATBAD, 61.8%
      and 44.0% for cATBAD-medical, 69.2% and 47.2% for cATBAD-open, and 68.0% and
      42.5% for cATBAD-thoracic endovascular aortic repair, respectively (P=0.001).
      Overall survival was significantly related primarily to complicated presentation.
      CONCLUSIONS: In our experience, early and late outcomes of ATBAD were dependent
      on the presence of complications, with cATBAD faring worse. Although uATBAD was
      associated with favorable early survival, late complications still occurred,
      mandating radiographic surveillance and open or endovascular interventions.
      Prospective trials are required to better determine the optimal therapy for
      uATBAD.

PMID- 26304667
TI  - Risk Factors for Abnormal Developmental Trajectories in Young Children With
      Congenital Heart Disease.
AB  - BACKGROUND: Children with congenital heart disease are at risk for developmental
      delay. This study sought to identify early risk factors for abnormal
      developmental trajectories in children with congenital heart disease. METHODS AND
      RESULTS: Children with congenital heart disease at high risk for developmental
      delay, without known genetic abnormality, and with >=3 assessments by the use of
      the Bayley Scales of Infant and Toddler Development, Third Edition, were studied.
      Logistic regression was used to assess the impact of patient and clinical factors
      on cognitive, language, and motor score trajectories; classified as: average or
      improved if all scores were >=85 (<1 standard deviation below the mean) or
      increased to >=85 and never decreased; or abnormal if all scores were <85, fell
      to <85 and never improved, or fluctuated above and below 85. Data on 131 children
      with 527 Bayley Scales of Infant and Toddler Development, Third Edition
      assessments were analyzed. Subject age was 5.5 to 37.4 months. Overall, 56% had
      cognitive, language, and motor development in the average range. Delays occurred
      in single domains in 23%. Multiple domains were delayed in 21%. More cardiac
      surgeries, longer hospital stay, poorer linear growth, and tube feeding were
      associated with worse outcomes in all domains (P<0.05). In the multivariable
      model, the need for tube feeding was a risk factor for having an abnormal
      developmental trajectory (odds ratio, 5.1-7.9). Minority race and lack of private
      insurance had significant relationships with individual domains. CONCLUSIONS:
      Longitudinal developmental surveillance identified early factors that can help
      quantify the risk of developmental delay over time. Strategies to improve
      modifiable factors and early therapeutic intervention can be targeted to children
      at highest risk.

PMID- 26304670
TI  - Correction.

PMID- 26304668
TI  - Microfluidic Single-Cell Analysis of Transplanted Human Induced Pluripotent Stem
      Cell-Derived Cardiomyocytes After Acute Myocardial Infarction.
AB  - BACKGROUND: Human induced pluripotent stem cells (iPSCs) are attractive
      candidates for therapeutic use, with the potential to replace deficient cells and
      to improve functional recovery in injury or disease settings. Here, we test the
      hypothesis that human iPSC-derived cardiomyocytes (iPSC-CMs) can secrete
      cytokines as a molecular basis to attenuate adverse cardiac remodeling after
      myocardial infarction. METHODS AND RESULTS: Human iPSCs were generated from skin
      fibroblasts and differentiated in vitro with a small molecule-based protocol.
      Troponin(+) iPSC-CMs were confirmed by immunohistochemistry, quantitative
      polymerase chain reaction, fluorescence-activated cell sorting, and
      electrophysiological measurements. Afterward, 2*10(6) iPSC-CMs derived from a
      cell line transduced with a vector expressing firefly luciferase and green
      fluorescent protein were transplanted into adult NOD/SCID mice with acute left
      anterior descending artery ligation. Control animals received PBS injection.
      Bioluminescence imaging showed limited engraftment on transplantation into
      ischemic myocardium. However, magnetic resonance imaging of animals transplanted
      with iPSC-CMs showed significant functional improvement and attenuated cardiac
      remodeling compared with PBS-treated control animals. To understand the
      underlying molecular mechanism, microfluidic single-cell profiling of harvested
      iPSC-CMs, laser capture microdissection of host myocardium, and in vitro ischemia
      stimulation were used to demonstrate that the iPSC-CMs could release significant
      levels of proangiogenic and antiapoptotic factors in the ischemic
      microenvironment. CONCLUSIONS: Transplantation of human iPSC-CMs into an acute
      mouse myocardial infarction model can improve left ventricular function and
      attenuate cardiac remodeling. Because of limited engraftment, most of the effects
      are possibly explained by paracrine activity of these cells.

PMID- 26304669
TI  - A Conductive Polymer Hydrogel Supports Cell Electrical Signaling and Improves
      Cardiac Function After Implantation into Myocardial Infarct.
AB  - BACKGROUND: Efficient cardiac function requires synchronous ventricular
      contraction. After myocardial infarction, the nonconductive nature of scar tissue
      contributes to ventricular dysfunction by electrically uncoupling viable
      cardiomyocytes in the infarct region. Injection of a conductive biomaterial
      polymer that restores impulse propagation could synchronize contraction and
      restore ventricular function by electrically connecting isolated cardiomyocytes
      to intact tissue, allowing them to contribute to global heart function. METHODS
      AND RESULTS: We created a conductive polymer by grafting pyrrole to the
      clinically tested biomaterial chitosan to create a polypyrrole (PPy)-chitosan
      hydrogel. Cyclic voltammetry showed that PPy-chitosan had semiconductive
      properties lacking in chitosan alone. PPy-chitosan did not reduce cell
      attachment, metabolism, or proliferation in vitro. Neonatal rat cardiomyocytes
      plated on PPy-chitosan showed enhanced Ca(2+) signal conduction in comparison
      with chitosan alone. PPy-chitosan plating also improved electric coupling between
      skeletal muscles placed 25 mm apart in comparison with chitosan alone,
      demonstrating that PPy-chitosan can electrically connect contracting cells at a
      distance. In rats, injection of PPy-chitosan 1 week after myocardial infarction
      decreased the QRS interval and increased the transverse activation velocity in
      comparison with saline or chitosan, suggesting improved electric conduction.
      Optical mapping showed increased activation in the border zone of PPy-chitosan
      treated rats. Echocardiography and pressure-volume analysis showed improvement in
      load-dependent (ejection fraction, fractional shortening) and load-independent
      (preload recruitable stroke work) indices of heart function 8 weeks after
      injection. CONCLUSIONS: We synthesized a biocompatible conductive biomaterial
      (PPy-chitosan) that enhances biological conduction in vitro and in vivo.
      Injection of PPy-chitosan better maintained heart function after myocardial
      infarction than a nonconductive polymer.

PMID- 26304671
TI  - Correction.

PMID- 26304672
TI  - Improving transport container design to reduce broiler chicken PSE (pale, soft,
      exudative) meat in Brazil.
AB  - Throughout the chicken production chain, transport from farm to the commercial
      abattoir is one of the most critical sources of stress, particularly heat stress.
      The aim of this work was to describe the performance of a new prototype truck
      container designed to improve the microenvironment and reduce the incidence of
      pale, soft and exudative (PSE) meat and dead on arrival (DOA) occurrences.
      Experiments were carried out for four different conditions: regular and prototype
      truck, both with and without wetting loaded cages at the farm (for bird thermal
      stress relief) just before transporting. While there was no difference in the DOA
      index (P >= 0.05), the prototype truck caused a reduction (P < 0.05) in the
      occurrence of PSE meat by 66.3% and 49.6% with and without wetting, respectively.
      The results of this experiment clearly revealed a low-cost solution for
      transporting chickens that yields better animal welfare conditions and improves
      meat quality. 

PMID- 26304673
TI  - A case of Capgras syndrome with one's own reflected image in a mirror.
AB  - We report the case of a 78-year-old patient admitted to the hospital for
      behavioral and psychological disorders consisting in impressions of presence of a
      stranger located behind the bathroom mirror, who strikingly shared the patient's
      appearance but was considered a different person, yet. We discuss how this case
      can be interpreted as an atypical Capgras syndrome for his mirror image and how
      it suggests an adjustment of the classical dual-route model that sustains face
      recognition between covert (or affective) and overt neural pathways. 

PMID- 26304674
TI  - Is electroconvulsive therapy safe in multiple sclerosis?

PMID- 26304675
TI  - Mental health service utilisation after a Community Treatment Order: A comparison
      between three modes of termination.
AB  - OBJECTIVE: Little work has examined Community Treatment Order processes,
      including mode of termination. This paper aimed to examine service utilisation
      and legal status following the Community Treatment Order termination by a review
      board, treating psychiatrist or expiry of order. METHOD: Data-linkage study
      following the service utilisation of those discharged from a Community Treatment
      Order of at least 3-month duration for the subsequent 2 years. We used the state
      wide database of all contacts with state-funded mental health services in
      Victoria, Australia. RESULTS: Of the 1478 patients who were discharged, 5% were
      discharged by the review board, 88% were discharged by the treating psychiatrist
      and in 7% the order expired. Logistic regression indicated that those discharged
      by the treating service were less likely to be subsequently placed under an
      involuntary order than those discharged by the Mental Health Review Board or
      those whose order had expired (odds ratio = 0.61). CONCLUSION: Poorly planned
      discharge as a result of expiry of the Community Treatment Order or abrupt
      discharge by the review board may be associated with a more severe relapse and
      subsequent need for compulsory treatment. The likelihood of being readmitted as
      an involuntary patient is greater for younger adults and those living in urban
      settings. In order to minimise the risk of major relapse, strong community
      engagement with treating services should be supported.

PMID- 26304676
TI  - Effect of short-chain fatty acids on triacylglycerol accumulation, lipid droplet
      formation and lipogenic gene expression in goat mammary epithelial cells.
AB  - Short-chain fatty acids (SCFAs) are the major energy sources for ruminants and
      are known to regulate various physiological functions in other species. However,
      their roles in ruminant milk fat metabolism are still unclear. In this study,
      goat mammary gland epithelial cells (GMECs) were treated with 3 mmol/L acetate,
      propionate or butyrate for 24 h to assess their effects on lipogenesis. Data
      revealed that the content of triacylglycerol (TAG) and lipid droplet formation
      were significantly stimulated by propionate and butyrate. The expression of
      FABP3, SCD1, PPARG, SREBP1, DGAT1, AGPAT6 and ADRP were upregulated by propionate
      and butyrate treatment. In contrast, the messenger RNA (mRNA) expression of FASN
      and LXRalpha was not affected by propionate, but reduced by butyrate. Acetate had
      no obvious effect on the content of TAG and lipid droplets but increased the mRNA
      expression of SCD1 and FABP3 in GMECs. Additionally, it was observed that
      propionate significantly increased the relative content of mono-unsaturated fatty
      acids (C18:1 and C16:1) at the expense of decreased saturated fatty acids (C16:0
      and C18:0). Butyrate and acetate had no significant effect on fatty acid
      composition. Overall, the results from this work help enhance our understanding
      of the regulatory role of SCFAs on goat mammary cell lipid metabolism. 

PMID- 26304677
TI  - Production of morphologically derived words in the semantic variant of primary
      progressive aphasia: preserved decomposition and composition but impaired
      validation.
AB  - Although there is growing interest in inflectional morphology in semantic variant
      primary progressive aphasia (svPPA), derivational morphology has rarely been
      studied in this population. This study reports the performance of N.G., a 72-year
      old-woman with svPPA in a verb production task designed to entail morphological
      processing (composition, decomposition) and self-appraisal of her productions.
      N.G. demonstrated an over-reliance on morphological processing and failures in
      her appraisal of root/affix combinations that resulted in the production of
      morphological paraphasias and neologisms. Her performance in lexical decision of
      verbs and pseudo-verbs points to the involvement of semantic impairment in these
      difficulties. 

PMID- 26304678
TI  - Easing the transition to secondary education for children with autism spectrum
      disorder: An evaluation of the Systemic Transition in Education Programme for
      Autism Spectrum Disorder (STEP-ASD).
AB  - In mainstream education, the transition from primary to secondary school ('school
      transition') is difficult for children with autism spectrum disorder, being
      marked by high levels of emotional and behavioural difficulties. The Systemic
      Transition in Education Programme for Autism Spectrum Disorder (STEP-ASD) is a
      new, manualised school transition intervention. We investigated its feasibility
      and efficacy for children diagnosed with autism spectrum disorder (N = 37; mean
      age = 11.47 years; mean IQ = 85.24) using an unblinded, non-randomised,
      controlled design. Teachers found the intervention feasible and acceptable.
      Children receiving STEP-ASD (n = 17) showed a large (Cohen's d = 0.88) reduction
      in school-reported emotional and behavioural difficulties, whereas controls (n =
      20) showed a slight increase (d = -0.1) (p = 0.010). These encouraging findings
      suggest the value of STEP-ASD as a low-intensity intervention for reducing
      problem behaviours and distress in children with autism spectrum disorder as they
      transition to mainstream secondary school.

PMID- 26304679
TI  - Intracranial epithelioid hemangioendothelioma causing subacute loss of vision.

PMID- 26304680
TI  - Myopia/heavy eye syndrome: a rare cause of horizontal diplopia.

PMID- 26304681
TI  - Author response.

PMID- 26304682
TI  - Biopsy-negative PET-positive giant-cell arteritis.

PMID- 26304683
TI  - Mystery Case: A 64-year-old woman with subacute encephalopathy.

PMID- 26304684
TI  - Can statins prevent seizures after strokes?

PMID- 26304685
TI  - Anthocyanin suppresses the toxicity of Abeta deposits through diversion of
      molecular forms in in vitro and in vivo models of Alzheimer's disease.
AB  - OBJECTIVES: The pathogenesis of Alzheimer's disease (AD) is strongly correlated
      with the aggregation and deposition of the amyloid beta (Abeta1-42) peptide in
      fibrillar form, and many studies have shown that plant-derived polyphenols are
      capable of attenuating AD progression in various disease models. In this study,
      we set out to correlate the effects of anthocyanoside extracts (Vaccinium
      myrtillus anthocyanoside (VMA)) obtained from bilberry on the in vitro
      progression of Abeta fibril formation with the in vivo effects of this compound
      on AD pathogenesis. METHODS: Thioflavin T fluorescence assays and atomic force
      microscopy were used to monitor Abeta amyloid formation in in vitro assays.
      Effects of Abeta amyloids on cellular viability were assayed using cultured
      Neuro2a cells. Cognitive effects were probed using mice that simultaneously
      expressed mutant human Abeta precursor and mutant presenilin-2. RESULTS: Addition
      of VMA inhibited the in vitro formation of Abeta peptide fibrils and also reduced
      the toxicity of these aggregates toward Neuro2a cells. A diet containing 1% VMA
      prevented the cognitive degeneration in AD mice. Curiously, this diet-derived
      retention of cognitive ability was not accompanied by a reduction in aggregate
      deposition in brains; rather, an increase in insoluble deposits was observed
      compared with mice raised on a control diet. DISCUSSION: The paradoxical increase
      in insoluble deposits caused by VMA suggests that these polyphenols divert Abeta
      aggregation to an alternate, non-toxic form. This finding underscores the complex
      effects that polyphenol compounds may exert on amyloid deposition in vivo.

PMID- 26304686
TI  - Genetic Risk Factors of Venous Thromboembolism in the East Algerian Population.
AB  - Many genetic risk factors have been identified for causing venous thromboembolism
      (VTE). Most of them affect the function of natural anticoagulant pathways,
      particularly the protein C system, although recent studies suggest a role of
      components of the hematopoietic pathway in the etiology of venous thrombosis. In
      this case-control study, we aimed to determine the frequency of prothrombin
      G20210A and factor V Leiden (FVL) G1691A polymorphisms and protein C, protein S,
      and antithrombin III deficiencies in the East Algerian population and to
      investigate whether these genetic factors are associated with VTE. On the other
      hand, our study tends to evaluate the status of JAK2V617F and calreticulin (CALR)
      mutations among these cases. The participants consisted of 121 cases with VTE and
      146 healthy controls. Polymorphisms of FVL G1691A and prothrombin G20210A were
      genotyped by polymerase chain reaction (PCR) restriction fragment length
      polymorphism. JAK2-V617F and calreticulin mutations were analyzed by quantitative
      PCR and PCR followed by capillary electrophoresis sequencing, respectively.
      Protein C, protein S, and antithrombin levels were determined and then hereditary
      deficiencies were identified. Of all cases and controls, none was a carrier of
      the antithrombin III deficiency, prothrombin gene G20210A, and CALR mutations.
      Only 1 case reported having a positive JAK2 mutation (mutant allele burden was
      15%). The FVL mutation (GA/AA) was found in 14 (11.6%) cases and 2 (1.4%)
      controls and it was significantly different between both the groups ( P = .001).
      Deficiencies of protein S and protein C were detected in 17 (18.8%) cases. The
      univariate analysis resulted in a significant impact of FVL (odds ratio [OR] =
      9.4, 95% confidence interval [CI] = 2.1-42.3; P = .003) and of protein S
      deficiency (OR = 16.9, 95% CI =2.1-132.8, P = .007) on the VTE status. Both
      factors stayed significant after adjustment for sex and age. The OR of the
      protein C deficiency was slightly elevated (OR = 6.4, 95% CI = 0.7-55.5), but it
      did not reach the level of statistical significance ( P = .091), and it was
      therefore not considered as a risk factor. In conclusion, coagulant factor V gene
      G1691A mutation and protein S deficiency constitute important genetic risk
      factors in patients with VTE in Eastern Algeria. The somatic mutation of JAK2
      V617F and CALR mutations are less frequent causes of VTE, thus routine testing
      for these mutations is not recommended.

PMID- 26304687
TI  - Emergence of a hypervirulent carbapenem-resistant Klebsiella pneumoniae isolate
      from clinical infections in China.
AB  - OBJECTIVES: Hypervirulent Klebsiella pneumoniae (hvKP) infections occur
      worldwide, but carbapenem-resistant hvKP strain has rarely been observed.
      METHODS: A retrospective study was conducted in 28 cases of carbapenem-resistant
      K. pneumoniae (CRKP) infections from 9 cities in China. Clinical data were
      collected from medical records. All the isolates were characterized by
      antimicrobial susceptibility testing, string test, multilocus sequence typing,
      and capsular genotyping. All the hypermucoviscous CRKP strains were analyzed by
      virulence gene profiles, serum killing assay, and mouse lethality assay. RESULTS:
      Of 28 CRKP isolates, five were positive for string test. Importantly, one of the
      hypermucoviscous strains isolated from blood sample was identified as hvKP. The
      hypervirulent CRKP strain showed highly resistant to carbapenems (MIC > 32
      MUg/mL), decreased expression of ompK35/36, and ESBLs production. Significantly
      increased resistance to serum killing and mice mortality were found in the
      hypervirulent CRKP strain compared to the other CRKPs. Capsular polysaccharide
      synthesis genotyping revealed that the hypervirulent strain belongs to K2
      serotype, while others belong to K-nontypable serotype. The K2 hypervirulent CRKP
      strain carried rmpA, aerobactin, entB, and mrkD genes. CONCLUSIONS: The newly
      emerged hypervirulent carbapenem-resistant K. pneumoniae might cause a serious
      threat to public health, suggesting an urgent need to enhance clinical awareness
      and epidemiologic surveillance.

PMID- 26304688
TI  - Is asymptomatic malaria really asymptomatic? Hematological, vascular and
      inflammatory effects of asymptomatic malaria parasitemia.
AB  - Asymptomatic malaria infections are highly prevalent in malaria endemic regions
      and most of these infections remain undiagnosed and untreated. Whereas
      conventional malaria symptoms are by definition absent, little is known on the
      more subtle health consequences of these infections. The aim of our study was to
      analyze the hematologic, vascular and inflammatory effects of patent and
      subpatent asymptomatic malaria parasitemia in children and adults on the
      Indonesian island Sumba. Both children and adults with parasitemia had increased
      high-sensitive C-reactive protein levels compared to aparasitemic individuals. In
      addition, children, but not adults with parasitemia also had lower platelet
      counts and Hb levels and higher levels of von Willebrand factor and platelet
      factor-4, markers of endothelial and platelet activation, respectively. These
      findings suggest that asymptomatic malaria infections have subtle health
      consequences, especially in children, and should be regarded as potentially
      harmful. 

PMID- 26304689
TI  - Oral antibiotics enhance antibody responses to keyhole limpet hemocyanin in
      orally but not muscularly immunized chickens.
AB  - Recent studies have emphasized the crucial role of gut microbiota in triggering
      and modulating immune response. We aimed to determine whether the modification of
      gut microbiota by oral co-administration of two antibiotics, ampicillin and
      neomycin, would lead to changes in the antibody response to antigens in chickens.
      Neonatal chickens were given or not given ampicillin and neomycin (0.25 and 0.5
      g/L, respectively) in drinking water. At 2 weeks of age, the chicks were
      muscularly or orally immunized with antigenic keyhole limpet hemocyanin (KLH),
      and then serum anti-KLH antibody levels were examined by ELISA. In orally
      immunized chicks, oral antibiotics treatment enhanced antibody responses (IgM,
      IgA, IgY) by 2-3-fold compared with the antibiotics-free control, while the
      antibiotics did not enhance antibody responses in the muscularly immunized
      chicks. Concomitant with their enhancement of antibody responses, the oral
      antibiotics also lowered the Lactobacillus species in feces. Low doses of
      antibiotics (10-fold and 100-fold lower than the initial trial), which failed to
      change the fecal Lactobacillus population, did not modify any antibody responses
      when chicks were orally immunized with KLH. In conclusion, oral antibiotics
      treatment enhanced the antibody response to orally exposed antigens in chickens.
      This enhancement of antibody response was associated with a modification of the
      fecal Lactobacillus content, suggesting a possible link between gut microbiota
      and antibody response in chickens. 

PMID- 26304690
TI  - Investigation on the interaction of cefpirome sulfate with lysozyme by
      fluorescence quenching spectroscopy and synchronous fluorescence spectroscopy.
AB  - The reaction mechanism of cefpirome sulfate with lysozyme at different
      temperatures (298, 310 and 318 K) was investigated using fluorescence quenching
      and synchronous fluorescence spectroscopy under simulated physiological
      conditions. The results clearly demonstrated that cefpirome sulfate caused strong
      quenching of the fluorescence of lysozyme by a static quenching mechanism. The
      binding constants obtained using the above methods were of the same order of
      magnitude and very similar. Static electric forces played a key role in the
      interaction between cefpirome sulfate and lysozyme, and the number of binding
      sites in the interaction was close to 1. The values of Hill's coefficients were >
      1, indicating that drugs or proteins showed a very weakly positive cooperativity
      in the system. In addition, the conclusions obtained from the two methods using
      the same equation were consistent. The results indicated that synchronous
      fluorescence spectrometry could be used to study the binding mechanism between
      drug and protein, and was a useful supplement to the fluorescence quenching
      method. In addition, the effect of cefpirome sulfate on the secondary structure
      of lysozyme was analyzed using circular dichroism spectroscopy.

PMID- 26304691
TI  - Formation of sulfur adducts of N-acetyl-p-benzoquinoneimine, an electrophilic
      metabolite of acetaminophen in vivo: participation of reactive persulfides.
AB  - While N-acetyl-p-benzoquinoneimine (NAPQI), an electrophilic metabolite of
      acetaminophen (APAP), has been found to undergo GSH conjugation associated with
      its detoxification, interaction of NAPQI with nucleophilic per- and polysulfides
      produced by cystathionine gamma-lyase (CSE), cystathionine beta-synthase, and/or
      other enzymes is not known. In the present study, we found that sulfur adducts
      such as the NAPQIH2-SSSCys adduct and the NAPQIH2-SSG adduct are produced in
      biological samples of mice upon APAP exposure. Our in vitro experiments indicated
      that the formation of these novel APAP metabolites is, at least in part,
      attributable to the interaction of CysSSnSH produced by CSE and GSH persulfide
      with APAP-derived NAPQI. 

PMID- 26304692
TI  - Social interaction in type 2 diabetes computer-mediated environments: How
      inherent features of the channels influence peer-to-peer interaction.
AB  - INTRODUCTION: Interventions via the internet provide support to individuals
      managing chronic illness. The purpose of this integrative review was to determine
      how the features of a computer-mediated environment influence social interactions
      among individuals with type 2 diabetes. METHODS AND DESIGN: A combination of MeSH
      and keyword terms, based on the cognates of three broad groupings: social
      interaction, computer-mediated environments, and chronic illness, was used to
      search the PubMed, PsychInfo, Sociology Research Database, and Cumulative Index
      to Nursing and Allied Health Literature databases. Eleven articles met the
      inclusion criteria. RESULTS: Computer-mediated environments enhance an
      individual's ability to interact with peers while increasing the convenience of
      obtaining personalized support. A matrix, focused on social interaction among
      peers, identified themes across all articles, and five characteristics emerged:
      (1) the presence of synchronous and asynchronous communication, (2) the ability
      to connect with similar peers, (3) the presence or absence of a moderator, (4)
      personalization of feedback regarding individual progress and self-management,
      and (5) the ability of individuals to maintain choice during participation.
      CONCLUSIONS: Individuals interact with peers to obtain relevant, situation
      specific information and knowledge about managing their own care. Computer
      mediated environments facilitate the ability of individuals to exchange this
      information despite temporal or geographical barriers that may be present, thus
      improving T2D self-management.

PMID- 26304693
TI  - Unsupervised learning based feature extraction for differential diagnosis of
      neurodegenerative diseases: A case study on early-stage diagnosis of Parkinson
      disease.
AB  - BACKGROUND: The development of MRI based methods could prove extremely valuable
      for identification of reliable biomarkers to aid diagnosis of neurodegenerative
      diseases (NDs). A great deal of current research has been aimed at identification
      biomarkers for both diagnosis at early stage and evaluation of the progression of
      NDs. NEW METHOD: We present here a novel synergetic paradigm integrating Kohonen
      self organizing map (KSOM) and least squares support vector machine (LS-SVM) for
      individual-level clinical diagnosis of NDs. Feature are extracted in an
      unsupervised manner using KSOM on preprocessed brain MRIs. Thereafter, these
      features are fed as input to LSSVM for subject classification. RESULTS: The
      applicability of the proposed methodology has been demonstrated using 831 T1
      weighted MRIs obtained from Parkinson's Progression Markers Initiative (PPMI)
      database. We have achieved classification accuracy of up to 99% for differential
      diagnosis of Parkinson disease with confidence interval of 99.9%. COMPARISON WITH
      OTHER EXISTING METHODS: The potential for translation of similar research
      findings to clinical application is greatly dependent upon two factors (1)
      accuracy of subject classification achieved and (2) size of the dataset used.
      Here, we report very high accuracy achieved on one of the largest MRI datasets
      using multivariate analysis tools. CONCLUSIONS: In this paper, we describe a
      methodology that has the potential to be translated into first-line diagnostic
      tool for NDs. We also demonstrate the applicability of this methodology for
      diagnosing PD subjects in early stages of the disease, i.e., subjects in age of
      31-60 years.

PMID- 26304694
TI  - Smoking to Regulate Negative Affect: Disentangling the Relationship Between
      Posttraumatic Stress and Emotional Disorder Symptoms, Nicotine Dependence, and
      Cessation-Related Problems.
AB  - INTRODUCTION: Posttraumatic stress disorder (PTSD) is associated with various
      aspects of cigarette smoking, including higher levels of nicotine dependence and
      cessation difficulties. Affect-regulatory smoking motives are thought to, in
      part, underlie the association between emotional disorders such as PTSD and
      smoking maintenance, although few studies have empirically tested this
      possibility. METHODS: Data were analyzed from 135 treatment-seeking smokers who
      were directly exposed to the World Trade Center disaster on September 11, 2001.
      We modeled the direct effect of 9/11 PTSD symptom severity on nicotine
      dependence, perceived barriers to smoking cessation, and severity of problematic
      symptoms experienced during prior cessation attempts. We also examined the
      indirect effect of PTSD on these outcomes via negative affect reduction smoking
      motives. Parallel models were constructed for additional emotional disorder
      symptoms, including panic and depressive symptoms. RESULTS: PTSD symptom severity
      was associated with nicotine dependence and perceived barriers to cessation, but
      not problems during prior quit attempts indirectly via negative affect reduction
      smoking motives. Panic and depressive symptoms both had significant indirect
      effects, via negative affect reduction smoking motives, on all three criterion
      variables. CONCLUSIONS: Affect-regulatory smoking motives appear to underlie
      associations between the symptoms of emotional disorders such as PTSD, panic, and
      depression in terms of smoking dependence and certain cessation-related criterion
      variables. IMPLICATIONS: Overall, this investigation suggests negative affect
      reduction smoking motives help to explain the relationship of PTSD, depression,
      and panic symptoms to nicotine dependence, severity of problems experienced
      during prior quit attempts and perceived barriers to cessation. These results
      highlight the importance of assessing motivations for smoking in the context of
      cessation treatment, especially among those with emotional disorder symptoms.
      Future interventions might seek to utilize motivational interviewing and
      cognitive restructuring techniques to address coping-oriented motives for
      smoking, in addition to skills for managing negative affect, as a means of
      improving quit outcomes.

PMID- 26304695
TI  - Integrative Medical Care Plus Mindfulness Training for Patients With Congestive
      Heart Failure: Proof of Concept.
AB  - Congestive heart failure (CHF) has a high rate of morbidity and mortality. It is
      often accompanied by other medical and psychosocial comorbidities that complicate
      treatment and adherence. We conducted a proof of concept pilot project to
      determine the feasibility of providing integrative group medical visits plus
      mindfulness training for patients recently discharged with CHF. Patients were
      eligible if they had been discharged from an inpatient stay for CHF within the 12
      months prior to the new program. The Compassionate Approach to Lifestyle and Mind
      Body (CALM) Skills for Patients with CHF consisted of 8 weekly visits focusing on
      patient education about medications, diet, exercise, sleep, and stress
      management; group support; and training in mind-body skills such as mindfulness,
      self-compassion, and loving-kindness. Over two 8-week sessions, 8/11 (73%)
      patients completed at least 4 visits. The patients had an average age of 57
      years. The most common comorbidities were weight gain, sleep problems, and
      fatigue. After the sessions, 100% of patients planned to make changes to their
      diet, exercise, and stress management practices. Over half of the patients who
      met with a pharmacist had a medication-related problem. Improvements were
      observed in depression, fatigue, and satisfaction with life. Integrative group
      visits focusing on healthy lifestyle, support, and skill-building are feasible
      even among CHF patients and should be evaluated in controlled trials as a patient
      centered approach to improving outcomes related to improving medication
      management, depression, fatigue, and quality of life. 

PMID- 26304696
TI  - Effects of summer heat stress on physiological variables, ovulation and
      progesterone secretion in Pelibuey ewes under natural outdoor conditions in an
      arid region.
AB  - Ten non-lactating multiparous Pelibuey breed ewes were housed in a corral to
      evaluate the effects of summer thermal stress on physiologic variables, estrous
      behavior, ovulation and corpus luteum functionality under natural conditions of
      an arid region. In summer and autumn, daily estrous detection with a ram fitted
      with an apron and blood sample collections were performed during two natural
      estrous cycles. An environment of heat stress was detected in summer and
      thermoneutral in autumn. Rectal temperature and respiratory frequency were
      greater (P < 0.01) in summer than in autumn during the morning and afternoon.
      Season did not affect (P > 0.05) live weight, body condition, length of estrous
      cycle or percentage of ewes in estrous and ovulating. Compared with autumn, serum
      progesterone concentrations in summer decreased (P < 0.05) between days 8 and 14
      of the estrous cycle. It is concluded that under outdoor conditions of arid
      regions, while estrous and ovulatory activities of Pelibuey ewes were not
      affected by summer thermal stress, the corpus luteum functionality was decreased.

PMID- 26304697
TI  - Attitudes of Primary Care Practitioners in Managing Chronic Pain Patients
      Prescribed Opioids for Pain: A Prospective Longitudinal Controlled Trial.
AB  - OBJECTIVE: There is increasing concern among primary care practitioners (PCPs)
      regarding medication misuse and noncompliance among chronic pain patients
      prescribed opioids for pain. This study investigated the benefits of
      interventions designed to track potential opioid misuse and to improve
      practitioner confidence in managing patients with chronic pain through the use of
      risk assessment, monthly monitoring of compliance, and specialty support.
      METHODS: Fifty-six PCPs and 253 chronic pain patients were recruited into the
      study. All patients were assessed for risk and called once a month for 6 months
      to monitor pain and opioid compliance. Practitioner knowledge about opioids,
      concerns about analgesic prescriptions, practice behavior, and attitudes of
      managing chronic pain patients were assessed and questionnaires were repeated
      after 1 year. Practitioners in the experimental group received monthly patient
      summary reports that consisted of pain, mood, activity levels, healthcare
      utilization, and results of the Opioid Compliance Checklist, while practitioners
      in the control group did not receive the monthly reports. RESULTS: After 1 year
      all the PCPs reported improvement in identifying patients at risk for misuse (P <
      0.05), perceived confidence in prescribing opioids for pain (P < 0.05) and
      increased satisfaction with communication with pain specialists (P < 0.05). The
      patients reported greater compliance with their opioid medication and felt that
      the monthly monitoring was beneficial. Despite modest improvements, many PCPs
      still lacked confidence in managing pain patients and reported reluctance to
      prescribe opioids for chronic noncancer pain, especially among younger
      practitioners. This study demonstrates the benefits of careful monitoring of
      chronic pain patients and need for pain management support within primary care.

PMID- 26304698
TI  - High plasma chemerin is associated with renal dysfunction and predictive for
      cardiovascular events - Insights from phenotype and genotype characterization.
AB  - The novel adipokine chemerin, encoded by the RARRES2 gene, has been suggested to
      be linked to insulin resistance and to the metabolic syndrome (MetS). However, no
      well-defined cardiovascular profile has been reported and the association with
      coronary artery disease (CAD) is a matter of debate. Because there is a relation
      between renal dysfunction and CAD, we analyzed plasma chemerin levels and the
      estimated glomerular filtration rate (eGFR) in 495 patients undergoing coronary
      angiography for the evaluation of established or suspected stable CAD. Chemerin
      levels were higher in patients with Type 2 diabetes mellitus (T2DM, n=111) and
      the metabolic syndrome (MetS, n=147) than in subjects without T2DM (191.5+/-72.9
      vs. 169.7+/-64.7ng/ml, p=0.001) or the MetS (201.2+/-71.0 vs. 163,1ng/ml,
      p<0.001), but did not differ significantly between patients with significant CAD
      (n=247) and those without significant CAD (177.1+/-67.0 vs. 171.7+/-67.2ng/ml,
      p=0.193). Analysis of covariance using age, sex, and BMI as covariates showed
      that chemerin was significantly and independently associated with eGFR (F=49.6,
      p<0.001). After an 8-year follow-up period, patients with high chemerin levels
      were more often affected by cardiovascular events (HR=1.72 [95% CI 1.19-2.47],
      p=0.004), even after appropriate adjustment for age, gender, BMI, as well as eGFR
      (adjusted HR 1.51 [95% CI 1.03-2.23], p=0.037). Given the cardiometabolic role of
      chemerin, we also applied a Cardio-Metabo Chip analysis and revealed a genome
      wide significant association with SNPs (rs55709438, rs2444030, and rs3098423)
      located at chromosomal region 15q15-23, which were associated with metabolic
      traits and eGFR. This study for the first time demonstrates that high chemerin
      concentrations are significantly associated with renal impairment and predictive
      of cardiovascular events and that 15q15-23 might have an impact on chemerin
      levels beyond common genetic variations in RARRES2. 

PMID- 26304699
TI  - Diminazene enhances stability of atherosclerotic plaques in ApoE-deficient mice.
AB  - Angiotensin (Ang) II contributes to the development of atherosclerosis, while Ang
      (1-7) has atheroprotective actions. Accordingly, angiotensin-converting enzyme 2
      (ACE2), which breaks-down Ang II and forms Ang-(1-7), has been suggested as a
      target against atherosclerosis. Here we investigated the actions of diminazene, a
      recently developed ACE2 activator compound, in a model of vulnerable
      atherosclerotic plaque. Atherosclerotic plaque formation was induced in the
      carotid artery of ApoE-deficient mice by a shear stress (SS) modifier device. The
      animals were treated with diminazene (15mg/kg/day) or vehicle. ACE2 was strongly
      expressed in the aortic root and low SS-induced carotid plaques, but poorly
      expressed in the oscillatory SS-induced carotid plaques. Diminazene treatment did
      not change the lesion size, but ameliorated the composition of aortic root and
      low SS-induced carotid plaques by increasing collagen content and decreasing both
      MMP-9 expression and macrophage infiltration. Interestingly, these beneficial
      effects were not observed in the oscillatory SS-induced plaque. Additionally,
      diminazene treatment decreased intraplaque ICAM-1 and VCAM-1 expression,
      circulating cytokine and chemokine levels and serum triglycerides. In summary,
      ACE2 was distinctively expressed in atherosclerotic plaques, which depends on the
      local pattern of shear stress. Moreover, diminazene treatment enhances the
      stability of atherosclerotic plaques. 

PMID- 26304701
TI  - Can nurse-led preoperative education reduce anxiety and postoperative
      complications of patients undergoing cardiac surgery?
AB  - BACKGROUND: The effect of preoperative education on anxiety and postoperative
      outcomes of cardiac surgery patients remains unclear. AIM: The aim of the study
      was to estimate the effectiveness of a nurse-led preoperative education on
      anxiety and postoperative outcomes. METHODS: A randomised controlled study was
      designed. All the patients who were admitted for elective cardiac surgery in a
      general hospital in Athens with knowledge of the Greek language were eligible to
      take part in the study. Patients in the intervention group received preoperative
      education by specially trained nurses. The control group received the standard
      information by the ward personnel. Measurements of anxiety were conducted on
      admission-A, before surgery-B and before discharge-C by the state-trait anxiety
      inventory. RESULTS: The sample consisted of 395 patients (intervention group:
      205, control group: 190). The state anxiety on the day before surgery decreased
      only in the intervention group (34.0 (8.4) versus 36.9 (10.7); P=0.001). The mean
      decrease in state score during the follow-up period was greater in the
      intervention group (P=0.001). No significant difference was found in the length
      of stay or readmission. Lower proportions of chest infection were found in the
      intervention group (10 (5.3) versus 1 (0.5); P=0.004). Multivariate linear
      regression revealed that education and score in trait anxiety scale on admission
      are independent predictors of a reduction in state anxiety. CONCLUSION:
      Preoperative education delivered by nurses reduced anxiety and postoperative
      complications of patients undergoing cardiac surgery, but it was not effective in
      reducing readmissions or length of stay.

PMID- 26304700
TI  - Orally active epoxyeicosatrienoic acid analog does not exhibit antihypertensive
      and reno- or cardioprotective actions in two-kidney, one-clip Goldblatt
      hypertensive rats.
AB  - This study examined the effects of a novel orally active 14,15
      epoxyeicosatrienoic acid analog (EET-A) on blood pressure (BP) and myocardial
      infarct size (IS) in two-kidney, one-clip (2K1C) Goldblatt hypertensive rats
      during sustained phase of hypertension. Between days 31 and 35 after clip
      placement the rats were treated with EET-A and BP was monitored by
      radiotelemetry; sham-operated normotensive rats were used as controls. Tissue
      concentrations of epoxyeicosatrienoic acids served as a marker of production of
      epoxygenase metabolites. The rats were subjected to acute myocardial
      ischemia/reperfusion (I/R) injury and IS was determined. We found that EET-A
      treatment did not lower BP in 2K1C rats and did not alter availability of
      biologically active epoxygenase metabolites in 2K1C or in sham-operated rats. The
      myocardial IS was significantly smaller in untreated 2K1C rats as compared with
      normotensive controls and EET-A reduced it in controls but not in 2K1C rats. Our
      findings suggest that during the phase of sustained hypertension 2K1C Goldblatt
      hypertensive rats exhibit increased cardiac tolerance to I/R injury as compared
      with normotensive controls, and that in this animal model of human renovascular
      hypertension short-term treatment with EET-A does not induce any antihypertensive
      and cardioprotective actions. 

PMID- 26304702
TI  - Development of a monoclonal antibody-based ELISA system for glyceraldehyde
      derived advanced glycation end products.
AB  - We have previously found that glyceraldehyde-derived advanced glycation end
      products (glycer-AGEs) elicit oxidative stress generation and evoke inflammatory
      and thrombotic reactions through their higher binding affinity to RAGE (receptor
      for AGEs), thereby playing a role in vascular complications in diabetes.
      Furthermore, circulating levels of glycer-AGEs are elevated in diabetes. We
      characterized a monoclonal antibody (mAb) raised against glycer-AGEs and prepared
      its specific ELISA system in human serum. We developed here mAb reacted
      specifically with glycer-AGEs or glyceraldehyde-derived pyridinium, but not other
      structurally identified AGEs or AGE precursors. The mAb not only completely
      neutralized the deleterious effects of glycer-AGEs on endothelial cells, but also
      detected glycer-AGEs in the aorta of type 2 diabetic rats. Intra and inter-assay
      coefficient variations of the ELISA were 6 and 2.6%, respectively. ELISA
      linearity was shown intact within 5-fold dilution, and recovery ratio of added
      glycer-AGEs was 88-117%. Results of serum and plasma were comparable, and
      repeated freeze-thawing of samples did not affect the results (90.1-112.4%).
      Serum glycer-AGEs levels in 30 healthy subjects evaluated by the ELISA were
      strongly correlated with those by polyclonal Ab-based one (r=0.82). Our present
      study suggests the clinical utility of mAb for evaluating glycer-AGE levels in
      both tissue and serum. 

PMID- 26304704
TI  - Animal models for studying dengue pathogenesis and therapy.
AB  - Development of a suitable animal model for dengue virus disease is critical for
      understanding pathogenesis and for preclinical testing of antiviral drugs and
      vaccines. Many laboratory animal models of dengue virus infection have been
      investigated, but the challenges of recapitulating the complete disease still
      remain. In this review, we provide a comprehensive coverage of existing models,
      from man to mouse, with a specific focus on recent advances in mouse models for
      addressing the mechanistic aspects of severe dengue in humans. This article forms
      part of a symposium in Antiviral Research on flavivirus drug discovery. 

PMID- 26304703
TI  - SCOPE of Pain: An Evaluation of an Opioid Risk Evaluation and Mitigation Strategy
      Continuing Education Program.
AB  - OBJECTIVE: Due to the high prevalence of prescription opioid misuse, the US Food
      and Drug Administration (FDA) mandated a Risk Evaluation and Mitigation Strategy
      (REMS) requiring manufacturers of extended-release/long-acting (ER/LA) opioid
      analgesics to fund continuing education based on a FDA Blueprint. This article
      describes the Safe and Competent Opioid Prescribing Education (SCOPE of Pain)
      program, an ER/LA opioid analgesic REMS program, and its impact on clinician
      knowledge, confidence, attitudes, and self-reported clinical practice. METHOD:
      Participants of the 3-h SCOPE of Pain training completed pre-, immediate post-
      and 2-month post-assessments. SUBJECTS: The primary target group (n = 2,850), and
      a subset (n = 476) who completed a 2-month post-assessment, consisted of
      clinicians licensed to prescribe ER/LA opioid analgesics, who care for patients
      with chronic pain and who completed the 3-h training between February 28, 2013
      and June 13, 2014. RESULTS: Immediately post-program, there was a significant
      increase in correct responses to knowledge questions (60% to 84%, P <= 0.02) and
      87% of participants planned to make practice changes. At 2-months post-program,
      there continued to be a significant increase in correct responses to knowledge
      questions (60% to 69%, P <= 0.03) and 67% reported increased confidence in
      applying safe opioid prescribing care and 86% reported implementing practice
      changes. There was also an improvement in alignment of desired attitudes toward
      safe opioid prescribing. CONCLUSIONS: The SCOPE of Pain program improved
      knowledge, attitudes, confidence, and self-reported clinical practice in safe
      opioid prescribing. This national REMS program holds potential to improve the
      safe use of opioids for the treatment of chronic pain.

PMID- 26304705
TI  - Selective inhibition of HIV-1 replication by the CDK9 inhibitor FIT-039.
AB  - FIT-039 has recently been identified as a novel cyclin-dependent kinase 9
      inhibitor with potent antiviral activity against a broad spectrum of DNA viruses,
      such as herpes simplex virus type 1 (HSV-1) and human cytomegaloviruses. In this
      study, FIT-039 was examined for its inhibitory effect on human immunodeficiency
      virus type 1 (HIV-1) replication in chronically infected cells. Its 50% effective
      concentration was 1.4-2.1MUM, irrespective of the cells used for antiviral
      assays, while its 50% cytotoxic concentration was >20MUM, indicating that FIT-039
      is a selective inhibitor of HIV-1 replication. FIT-039 also inhibited HIV-1 RNA
      expression in a dose-dependent fashion. Since previous studies demonstrated that
      FIT-039 exhibited antiviral efficacy without noticeable adverse effects in HSV-1
      infected mice, the compound should be further investigated for its clinical
      potential against HIV-1 infection. 

PMID- 26304706
TI  - Temporary sobriety initiatives as public pedagogy: Windows of opportunity for
      embodied learning.
AB  - Philanthropic temporary sobriety initiatives such as Dry July, FebFast and
      Ocsober have become increasingly popular in Australia and have begun to spread to
      other locations both for their fundraising potential and as a grassroots public
      health measure to promote more responsible attitudes to alcohol consumption. This
      article presents findings from a series of in-depth, post-campaign interviews
      with FebFast 2014 participants and staff about how these campaigns can be
      understood as a form of public pedagogy or non-traditional learning that
      purposefully cultivates and suggests health-promoting meanings for embodied
      experience. It explicates the mechanisms of public pedagogies that rely on
      embodiment and, importantly, considers the learner's perspective on the
      pedagogical process. Temporary sobriety initiatives are found to operate thanks
      to (1) a structure that prescribes and facilitates short-term changes and
      enforces compliance with a social contract of philanthropy and (2) messaging that
      guides participants in their evaluation and assessment of their experience of
      temporary sobriety as physically and psychologically beneficial, as well as
      socially informative and impactful.

PMID- 26304707
TI  - Narrative approaches in mental health: Preserving the emancipatory tradition.
AB  - Narrative approaches have exercised an emancipatory influence within mental
      health. In this article, it is suggested that there is a risk that the
      emancipatory tradition associated with narrative may be co-opted through
      contemporary mental health strategy by a narrow agenda which promotes a
      particular Western and neoliberal form of citizenship. This may limit the way
      recovery can be imagined by equating it solely with the future-orientated
      individual who strives, above all, to be economically independent. To resist
      this, it is suggested that narrative in mental health should be approached with
      recourse to therapeutic thinking which promotes a relational ethos of 'recovery
      together'. The 'recovery together' model is subsequently considered in relation
      to narrative research on temporal understandings which have been conducted in
      disability studies and in the area of chronic illness. These studies point
      towards the value of a relational orientation towards well-being in the present,
      rather than fixating on future goals. It is suggested that a relational
      philosophy of the present might be usefully incorporated into narrative
      approaches when working therapeutically with people suffering from mental
      distress. It is argued that this might enable users and practitioners to extend
      the available narrative templates and to imagine recovery in diverse ways which
      support personal transformation and, ultimately, contribute to social change.

PMID- 26304708
TI  - Effect of farm characteristics and practices on hygienic quality of ovine raw
      milk used for artisan cheese production in central Italy.
AB  - A survey on ovine dairy farms directly transforming own-produced milk, in the
      Italian Marche region, was carried out to assess flock and milking practices that
      may influence milk hygienic-sanitary conditions. A census survey established that
      24 dairy farms were located in this region. Bulk milk samples were collected
      throughout the milking period in each dairy farm in 2013. Analyzed variables
      were: (i) chemical parameters such as fat, protein and lactose content, dry
      matter and pH; and (ii) total bacterial (TBC) and somatic cell counts (SCC).
      Chemical parameter values were in agreement with published data while, geometric
      mean (GM) log10 SCC was 5.91 and TBC GM was 57 978 colony forming units/mL, in
      compliance with Eropean Union criteria. A positive correlation was found between
      SCC and TBC when GMs of all farm data were considered (Spearman's rho = 0.7925; P
      = 0.0001). Statistical analysis did not show significant correlation between SCC
      or TBC GM and dairy farm principal characteristics. Although SCC levels detected
      in the present study should suggest the need to implement mastitis control
      programs, Marche's dairy sheep flocks revealed a good hygienic condition level.
      This is an important aspect in implementing safety for end users of the final
      product.

PMID- 26304709
TI  - Young Adults' Risk Perceptions of Various Tobacco Products Relative to
      Cigarettes: Results From the National Young Adult Health Survey.
AB  - Objectives Tobacco product risk perceptions may influence whether individuals use
      those products instead of or in addition to regular cigarettes. This study aimed
      to explore risk perceptions of various tobacco products relative to traditional
      cigarettes with young adults, a group with higher rates of tobacco use. Method We
      examined risk perception responses among a nationally representative sample of
      young adults (age 18-34 years; n = 2,871, including tobacco and non-tobacco
      users) from the 2011 National Young Adult Health Survey. Results Most (57.8%)
      respondents believed that e-cigarettes were less risky than cigarettes.
      Respondents were more likely to rate combustible products hookah (24.5%) and
      cigars (13.9%) as being less risky compared to noncombustible snus (10%) and
      other smokeless tobacco (SLT) products (7.1%) relative to cigarettes. Few (2.5%)
      rated menthol cigarettes as less risky. For e-cigarettes, hookah, and SLT, less
      risky beliefs were significantly higher among ever or current versus never
      product users. Between 22% and 33% of all respondents believed that SLT, snus,
      menthol cigarettes, and cigars were more risky than cigarettes, but differences
      in this belief between current and nonusers of these products were small and
      insignificant. Younger young adults were more likely to rate e-cigarettes and
      hookah as being "less risky" and rate cigars and SLT as being "more risky" than
      older young adults. Conclusion The public's views of comparative tobacco risk
      perceptions vary widely by tobacco product type and age-group. While "less risky"
      perceptions may be associated with product use, perceptions that products are
      "more risky" than cigarettes may not necessarily dissuade people from their use.

PMID- 26304710
TI  - Caregiver's Country of Birth Is a Significant Determinant of Accurate Perception
      of Preschool-Age Children's Weight.
AB  - BACKGROUND: One in four preschool-age children in the United States are currently
      overweight or obese. Previous studies have shown that caregivers of this age
      group often have difficulty accurately recognizing their child's weight status.
      The purpose of this study was to examine factors associated with
      accurate/inaccurate perception of child body mass index (BMI) among a
      multicultural sample of caregivers who were predominantly low-income and foreign
      born. METHODS: A total of 980 caregivers (72% Hispanic, 71% born outside of the
      United States) of preschool-age children (N= 1,105) were asked if their child was
      normal weight, overweight, or obese. Answers were compared to actual child BMI
      percentile category via chi-square analysis. Logistic regression analysis was
      performed to assess predictors of accurate perception of child BMI percentile
      category. RESULTS: More than one third of preschoolers were either overweight
      (18.4%) or obese (16.5%). The majority (92%) of caregivers of an overweight/obese
      child inaccurately perceived that their child was in a normal BMI category.
      Overall, foreign-born caregivers were significantly less likely to accurately
      perceive their child's BMI percentile category versus U.S.-born caregivers (odds
      ratio [OR] = 0.65, 95% confidence interval [CI] = 0.48-0.88). Specifically, those
      born in South America (OR = 0.59, 95% CI = 0.36-0.98), Central America/Mexico (OR
      = 0.59, 95% CI = 0.41-0.85), and Caribbean Hispanic nations (OR = 0.54, 95% CI =
      0.35-0.83) were significantly less likely to accurately perceive their child's
      BMI category versus U.S.-born caregivers. CONCLUSIONS: The results of this study
      suggest that foreign-born caregivers of U.S. preschool-age overweight/obese
      children in particular do not accurately perceive their child's BMI status.
      Health care professionals serving foreign-born caregivers may consider additional
      culturally appropriate healthy weight counseling for these families.

PMID- 26304711
TI  - Bullied Status and Physical Activity in Texas Adolescents.
AB  - This study examined the association between having been bullied at school during
      the past 6 months ("bullied status") and not meeting physical activity (PA)
      recommendations of 60 minutes of daily PA during the past week among 8th- and
      11th-grade Texas adolescents. Multiple logistic regression analysis was conducted
      to examine this association, adjusted for weight status, grade, race/ethnicity,
      and stratified by gender; furthermore, a significant interaction was found
      between bullied status and weight status. Results are presented by interaction
      status. Results indicated that overweight girls who reported never being bullied,
      as well as those who reported being bullied more than twice, had higher odds of
      not meeting PA recommendations than normal weight girls who were never bullied
      (adjusted odds ratio [AOR] = 2.12, 95% confidence interval [CI: 1.12, 3.99]; AOR
      = 9.18, 95% CI [2.26, 37.27], respectively). Obese girls who were bullied once or
      twice had higher odds of not meeting PA recommendations than normal weight girls
      who were never bullied (AOR = 2.89, 95% CI [1.06, 7.89]). Overweight boys who
      reported never being bullied had lower odds of not meeting PA recommendations
      than normal weight boys who were never bullied (AOR = 0.62, 95% CI [0.39, 0.97]).
      Conversely, obese boys who were bullied once or twice reported higher odds of not
      meeting PA recommendations than normal weight boys who were never bullied (AOR =
      3.61, 95% CI [1.22, 10.67]). Findings from this study indicate that the
      association between bullied status and meeting PA recommendations is complex and
      may differ by gender and the interaction between bullied status and weight
      status.

PMID- 26304712
TI  - Radiofrequency catheter ablation of ventricular arrhythmias originating from the
      continuum between the aortic sinus of Valsalva and the left ventricular summit:
      Electrocardiographic characteristics and correlative anatomy.
AB  - BACKGROUND: Radiofrequency ablation of ventricular arrhythmias (VAs) originating
      from the continuum between the aortic sinus of Valsalva (ASV) and the left
      ventricular (LV) summit is a challenge. OBJECTIVES: The objectives of this study
      were to investigate the electrocardiographic, electrophysiological, and
      anatomical characteristics of VAs and to develop an algorithm for predicting the
      successful ablation site. METHODS: We recruited 66 patients (mean age, 47 +/- 15
      years; 42 male patients) with symptomatic VAs originating from the continuum
      between the ASV and the LV summit who underwent radiofrequency ablation. Patients
      were classified into 4 groups (group 1: ASV, n = 20; group 2: subvalvular region,
      n = 15; group 3: great cardiac vein/anterior interventricular vein [GCV/AIV], n =
      16; group 4: epicardium requiring pericardial access, n = 15). The QRS
      morphological characteristics of VAs were compared between the 4 groups. RESULTS:
      Electrocardiographic analysis revealed that the aVL/aVR Q-wave ratio is useful in
      the prediction of successful ablation sites in the ASV, subvalvular area,
      GCV/AIV, and epicardium requiring pericardial access at cutoff values of <=1.415,
      1.416-1.535, 1.536-1.740, and >1.740, respectively. The aVL/aVR Q-wave ratio was
      well correlated with the distance between the successful ablation site and the
      tip of the LV summit. A distance of >18.9 mm and an LV myocardial thickness of
      >9.1 mm predicted the need for the epicardial or GCV/AIV approaches. There were
      no major procedural complications. Eight patients (12.1%) developed VA recurrence
      during a mean follow-up of 15.9 months (interquartile range 9.2-24.2 months).
      CONCLUSION: The aVL/aVR Q-wave ratio is a useful parameter for predicting the
      successful ablation sites of VAs originating from the continuum between the ASV
      and the LV summit.

PMID- 26304714
TI  - Position and sensing vector-related triple counting and inappropriate shocks in
      the subcutaneous implantable cardioverter-defibrillator system.

PMID- 26304713
TI  - Importance of non-pulmonary vein triggers ablation to achieve long-term freedom
      from paroxysmal atrial fibrillation in patients with low ejection fraction.
AB  - BACKGROUND: Whether ablation of non-pulmonary vein (PV) triggers after pulmonary
      vein antrum isolation (PVAI) improves the long-term procedure outcome in patients
      with paroxysmal atrial fibrillation (PAF) and left ventricular systolic
      dysfunction is unknown. OBJECTIVE: We sought to evaluate whether a more extensive
      ablation procedure improves outcomes at follow-up. METHODS: Consecutive patients
      with PAF refractory to antiarrhythmic drugs presenting for PVAI were
      prospectively studied. Patients were categorized into 2 groups: patients with
      left ventricular ejection fraction (LVEF) <=35% (group I; n = 175) and patients
      with LVEF >=50% (group II; n = 545). Patients in group I were further divided
      according to whether additional ablation of non-PV triggers was performed (group
      IA; n = 88) or not (group IB; n = 87). Long-term ablation success off
      antiarrhythmic drugs after a single procedure was analyzed. RESULTS: Patients in
      group I had more non-PV triggers than did patients in group II (69.1% vs 26.6%; P
      < .001). During a follow-up of 15.8 +/- 4.7 months, fewer patients in group I
      remained free from recurrences than those in group II (53.7% vs 81.7%; P < .001).
      Long-term ablation success was higher in group IA than in group IB (75.0% vs
      32.2%; P < .001) and similar to that in group II (75.0% vs 81.7%; P = .44). In
      multivariate analysis, LVEF <=35% (hazard ratio 1.68; P = .003) and non-PV
      triggers (hazard ratio 3.12; P < .001) were independent predictors of
      recurrences. CONCLUSION: In patients with PAF and left ventricular systolic
      dysfunction, ablation of non-PV triggers in addition to PVAI significantly
      improves their long-term procedure outcome.

PMID- 26304715
TI  - High interobserver variability in the assessment of epsilon waves: Implications
      for diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia.
AB  - BACKGROUND: Revision of the Task Force diagnostic criteria for arrhythmogenic
      right ventricular cardiomyopathy/dysplasia (ARVC/D) has increased their
      sensitivity for the diagnosis of early and familial forms of the disease. The
      epsilon wave is a major diagnostic criterion in the context of ARVC/D, which,
      however, remains not quantifiable and therefore may leave room for substantial
      subjective interpretation. OBJECTIVE: The purpose of this study was to assess
      interobserver agreement in epsilon wave definition and epsilon wave importance
      for ARVC/D diagnosis. METHODS: Electrocardiographic (ECG) tracings depicting
      leads V1, V2, and V3 collected from individuals evaluated for ARVC/D (n = 30)
      were given to panel members who were asked to respond to the question whether ECG
      patterns meet epsilon wave definition outlined by the Task Force diagnostic
      criteria. The prevalence and importance of epsilon waves for ARVC/D diagnosis
      were assessed in a pooled data set of patients with definite ARVC/D from European
      and American registries (n = 815). RESULTS: The number of ECG patterns identified
      as epsilon waves varied from 5 to 18 per reviewer (median 13 per reviewer). A
      unanimous agreement was reached for only 10 cases (33%), 2 of which qualified as
      epsilon waves and 8 as non-epsilon waves by all panel members. From a pooled data
      set, 106 patients reportedly had epsilon waves (13%). In 105 of 106 patients with
      epsilon waves (99%), exclusion of epsilon waves from the diagnostic score would
      not affect the "definite" diagnostic category. CONCLUSION: Interobserver
      variability in the assessment of epsilon waves is high; however, the impact of
      epsilon waves on ARVC/D diagnosis is negligibly low. The results urge to exercise
      caution in the assessment of epsilon waves, especially in patients who would not
      otherwise meet diagnostic criteria.

PMID- 26304716
TI  - Radiosensitization of metformin in pancreatic cancer cells via abrogating the G2
      checkpoint and inhibiting DNA damage repair.
AB  - Recent evidences have demonstrated the potential of metformin as a novel agent
      for cancer prevention and treatment. Here, we investigated its ability of
      radiosensitization and the underlying mechanisms in human pancreatic cancer
      cells. In this study, we found that metformin at 5 mM concentration enhanced the
      radiosensitivity of MIA PaCa-2 and PANC-1 cells, with sensitization enhancement
      ratios of 1.39 and 1.27, respectively. Mechanistically, metformin caused
      abrogation of the G2 checkpoint and increase of mitotic catastrophe, associated
      with suppression of Wee1 kinase and in turn CDK1 Tyr15 phosphorylation.
      Furthermore, metformin inhibited both expression and irradiation-induced foci
      formation of Rad51, a key player in homologous recombination repair, ultimately
      leading to persistent DNA damage, as reflected by gamma-H2AX and 53BP1 signaling.
      Finally, metformin-mediated AMPK/mTOR/p70S6K was identified as a possible
      upstream pathway controlling translational regulation of Wee1 and Rad51. Our data
      suggest that metformin radiosensitizes pancreatic cancer cells in vitro via
      abrogation of the G2 checkpoint and inhibition of DNA damage repair. However, the
      in vivo study is needed to further confirm the findings from the in vitro study. 

PMID- 26304717
TI  - Enhanced anti-colon cancer immune responses with modified eEF2-derived peptides.
AB  - Eukaryotic elongation factor-2 (eEF2) is overexpressed in many human cancers and
      is an attractive target for cancer immunotherapy. The eEF2 derived polypeptides
      have been shown to be able to induce cytotoxic T lymphocytes from healthy donor.
      Here, we demonstrate the evidence indicating that modification of a segment of
      peptides from wild type eEF2-derived immunogenic peptides is able to further
      enhance its capacity of inducing antigen-specific cytotoxic T lymphocytes (CTLs)
      against colon cancer cells. Using peptide-MHC binding algorithms, potential HLA
      A2.1-restricted epitopes capable of inducing specific CD8(+) CTLs were
      identified. By analyzing HLA-A2.1 affinity and immunogenicity, we further
      identified one novel immunogenic peptide, P739-747 (RLMEPIYLV), that elicited
      specific CTL responses in HLA-A2.1/K(b) transgenic mice and culture with
      peripheral blood lymphocytes from colon cancer patients. Furthermore, replacing
      certain amino acids (at positions 1, 3, 7) within the P739-747 sequence improved
      the immunogenicity against eEF2. Several analogs containing the auxiliary HLA
      A*0201 anchor residues were able to stably bind to HLA-A*0201 and enhance CTL
      responses compared with the native sequence; two of them showed increased anti
      tumor effects during the adoptive immunotherapy in vivo. Thus, these results
      support that modified immunogenic analogs are promising candidates for peptide
      based cancer vaccination and immunotherapy. 

PMID- 26304718
TI  - Compensatory postural adjustments in Parkinson's disease assessed via a virtual
      reality environment.
AB  - Postural control is a complex dynamic mechanism, which integrates information
      from visual, vestibular and somatosensory systems. Idiopathic Parkinson's disease
      (IPD) patients are unable to produce appropriate reflexive responses to changing
      environmental conditions. Still, it is controversial what is due to voluntary or
      involuntary postural control, even less what is the effect of levodopa. We aimed
      to evaluate compensatory postural adjustments (CPA), with kinematic and time
      frequency analyzes, and further understand the role of dopaminergic medication on
      these processes. 19 healthy subjects (Controls) and 15 idiopathic Parkinson's
      disease (IPD) patients in the OFF and ON medication states, wearing IMUs, were
      submitted to a virtual reality scenario with visual downward displacements on a
      staircase. We also hypothesized if CPA would involve mechanisms occurring in
      distinct time scales. We subsequently analyzed postural adjustments on two
      frequency bands: low components between 0.3 and 1.5 Hz (LB), and high components
      between 1.5 and 3.5 Hz (HB). Vertical acceleration demonstrated a greater power
      for discriminating IPD patients from healthy subjects. Visual perturbation
      significantly increased the power of the HB in all groups, being particularly
      more evident in the OFF state. Levodopa significantly increased their basal power
      taking place on the LB. However, controls and IPD patients in the ON state
      revealed a similar trend of the control mechanism. Results indicate an
      improvement in muscular stiffness provided by levodopa. They also suggest the
      role of different compensatory postural adjustment patterns, with LB being
      related to inertial properties of the oscillating mass and HB representing
      reactions to the ongoing visual input-changing scenario.

PMID- 26304719
TI  - Widespread cerebellar transcriptome changes in Ts65Dn Down syndrome mouse model
      after lifelong running.
AB  - Our previous study showed an improvement in locomotor deficits after voluntary
      lifelong running in Ts65Dn mice, an animal model for Down syndrome (DS). In the
      present study, we employed mouse microarrays printed with 55,681 probes in an
      attempt to identify molecular changes in the cerebellar transcriptome that might
      contribute to the observed behavioral benefits of voluntary long-term running in
      Ts65Dn mice. Euploid mice were processed in parallel for comparative purposes in
      some analyses. We found that running significantly changed the expression of
      4,315 genes in the cerebellum of Ts65Dn mice, over five times more than in
      euploid animals, up-regulating 1,991 and down-regulating 2,324 genes. Functional
      analysis of these genes revealed a significant enrichment of 92 terms in the
      biological process category, including regulation of biosynthesis and metabolism,
      protein modification, phosphate metabolism, synaptic transmission, development,
      regulation of cell death/apoptosis, protein transport, development, neurogenesis
      and neuron differentiation. The KEGG pathway database identified 18 pathways that
      are up-regulated and two that are down-regulated by running that were associated
      with learning, memory, cell signaling, proteolysis, regeneration, cell cycle,
      proliferation, growth, migration, and survival. Of six mRNA protein products we
      tested by immunoblotting, four showed significant running-associated changes in
      their levels, the most prominent in glutaminergic receptor metabotropic 1, and
      two showed changes that were close to significant. Thus, unexpectedly, our data
      point to the high molecular plasticity of Ts65Dn mouse cerebellum, which
      translated into humans with DS, suggests that the motor deficits of individuals
      with DS could markedly benefit from prolonged exercise. 

PMID- 26304720
TI  - Roles of the pre-SMA and rIFG in conditional stopping revealed by transcranial
      magnetic stimulation.
AB  - Although both the presupplementary motor area (pre-SMA) and the right inferior
      frontal gyrus (rIFG) have been demonstrated to be critical for response
      inhibition, there is still considerable disagreement over the roles they play in
      the process. In the present study, we investigated the causal relations of the
      pre-SMA and the rIFG in a conditional stop-signal task by applying offline theta
      burst transcranial magnetic stimulation. The task introduced a continue
      condition, which requires the same motor response as in a go trial but captures
      attention as in a stop trial. We found great individual differences in the amount
      of slowing on continue trials. Temporary suppression of pre-SMA activity
      prolonged the continue RT in participants who slowed little in response to
      continue trials, whereas disruption of the rIFG did not lead to significant
      changes in performance irrespective of the degree of slowing. Our results
      contribute to the understanding of the role of the pre-SMA by providing causal
      evidence that it is involved in response slowing on continue trials during
      conditional stopping, and it is likely that its efficiency in updating motor
      planning and reinitiating an inhibited response was associated with the amount of
      slowing. 

PMID- 26304721
TI  - Endocervical Atypical Polypoid Adenomyoma.
AB  - Atypical polypoid adenomyomas (APAMs) are rare uterine tumors that occur
      predominantly in premenopausal women, with less than 250 cases reported so far,
      worldwide. They may recur after treatment, and they may coexist with, or precede
      development of an endometrial adenocarcinoma. For this reason cases managed with
      conservative surgery or medical therapies require long-term follow-up. We report
      the case of a 41 years old nulliparous patient who during a diagnostic
      hysteroscopy was found with an endocervical atypical polypoid adenomyoma (APAM).
      The patient was desirous of a pregnancy, reported menometrorrhagia, and had a
      coexistent 5 cm, grade 2, submucous myoma, 3 endometrial polyps, and diffuse
      adenomyosis. She was treated with hysteroscopic resection of the APAM and polyps,
      plus laparoscopic myomectomy and wedge resection of adenomyosis. She is on an IVF
      list and after 4 months she is symptoms-free.

PMID- 26304722
TI  - Lesions of the Pouch of Douglas: A Review.
AB  - The pouch of Douglas may become occupied by a variety of mass-like lesions, which
      may be challenging to providers who treat women. These lesions may initially be
      thought to arise from the uterus or adnexa. We conducted a literature review
      using a Medline search of the terms "Douglas' pouch," "pouch of Douglas," "cul-de
      sac," and "rectouterine pouch." A review of the scope of pouch of Douglas lesions
      is presented to assist in developing a differential diagnosis if a patient with
      such a lesion is encountered. 

PMID- 26304723
TI  - Protein kinase D promotes plasticity-induced F-actin stabilization in dendritic
      spines and regulates memory formation.
AB  - Actin turnover in dendritic spines influences spine development, morphology, and
      plasticity, with functional consequences on learning and memory formation. In
      nonneuronal cells, protein kinase D (PKD) has an important role in stabilizing F
      actin via multiple molecular pathways. Using in vitro models of neuronal
      plasticity, such as glycine-induced chemical long-term potentiation (LTP), known
      to evoke synaptic plasticity, or long-term depolarization block by KCl, leading
      to homeostatic morphological changes, we show that actin stabilization needed for
      the enlargement of dendritic spines is dependent on PKD activity. Consequently,
      impaired PKD functions attenuate activity-dependent changes in hippocampal
      dendritic spines, including LTP formation, cause morphological alterations in
      vivo, and have deleterious consequences on spatial memory formation. We thus
      provide compelling evidence that PKD controls synaptic plasticity and learning by
      regulating actin stability in dendritic spines. 

PMID- 26304724
TI  - Mast cells and dendritic cells form synapses that facilitate antigen transfer for
      T cell activation.
AB  - Mast cells (MCs) produce soluble mediators such as histamine and prostaglandins
      that are known to influence dendritic cell (DC) function by stimulating
      maturation and antigen processing. Whether direct cell-cell interactions are
      important in modulating MC/DC function is unclear. In this paper, we show that
      direct contact between MCs and DCs occurs and plays an important role in
      modulating the immune response. Activation of MCs through FcepsilonRI cross
      linking triggers the formation of stable cell-cell interactions with immature DCs
      that are reminiscent of the immunological synapse. Direct cellular contact
      differentially regulates the secreted cytokine profile, indicating that MC
      modulation of DC populations is influenced by the nature of their interaction.
      Synapse formation requires integrin engagement and facilitates the transfer of
      internalized MC-specific antigen from MCs to DCs. The transferred material is
      ultimately processed and presented by DCs and can activate T cells. The
      physiological outcomes of the MC-DC synapse suggest a new role for intercellular
      crosstalk in defining the immune response. 

PMID- 26304725
TI  - APC is required for muscle stem cell proliferation and skeletal muscle tissue
      repair.
AB  - The tumor suppressor adenomatous polyposis coli (APC) is a crucial regulator of
      many stem cell types. In constantly cycling stem cells of fast turnover tissues,
      APC loss results in the constitutive activation of a Wnt target gene program that
      massively increases proliferation and leads to malignant transformation. However,
      APC function in skeletal muscle, a tissue with a low turnover rate, has never
      been investigated. Here we show that conditional genetic disruption of APC in
      adult muscle stem cells results in the abrogation of adult muscle regenerative
      potential. We demonstrate that APC removal in adult muscle stem cells abolishes
      cell cycle entry and leads to cell death. By using double knockout strategies, we
      further prove that this phenotype is attributable to overactivation of beta
      catenin signaling. Our results demonstrate that in muscle stem cells, APC dampens
      canonical Wnt signaling to allow cell cycle progression and radically diverge
      from previous observations concerning stem cells in actively self-renewing
      tissues. 

PMID- 26304726
TI  - An organelle-exclusion envelope assists mitosis and underlies distinct molecular
      crowding in the spindle region.
AB  - The mitotic spindle is a microtubular assembly required for chromosome
      segregation during mitosis. Additionally, a spindle matrix has long been proposed
      to assist this process, but its nature has remained elusive. By combining live
      cell imaging with laser microsurgery, fluorescence recovery after photobleaching,
      and fluorescence correlation spectroscopy in Drosophila melanogaster S2 cells, we
      uncovered a microtubule-independent mechanism that underlies the accumulation of
      molecules in the spindle region. This mechanism relies on a membranous system
      surrounding the mitotic spindle that defines an organelle-exclusion zone that is
      conserved in human cells. Supported by mathematical modeling, we demonstrate that
      organelle exclusion by a membrane system causes spatio-temporal differences in
      molecular crowding states that are sufficient to drive accumulation of mitotic
      regulators, such as Mad2 and Megator/Tpr, as well as soluble tubulin, in the
      spindle region. This membranous "spindle envelope" confined spindle assembly, and
      its mechanical disruption compromised faithful chromosome segregation. Thus,
      cytoplasmic compartmentalization persists during early mitosis to promote spindle
      assembly and function. 

PMID- 26304728
TI  - A Case for the Chronic Disease Management and the Integrated Care Model for Pain
      Medicine: An Affordable Care Act Imperative and Global Trend.

PMID- 26304729
TI  - Changes in diarrhea, nutrients apparent digestibility, digestive enzyme
      activities of weaned piglets in response to chitosan-zinc chelate.
AB  - A total of 120 weanling barrows weighing 6.11 +/- 0.20 kg were randomly allotted
      to four treatments with three replications (i.e. pen) of ten piglets per
      replicate. Pigs were received corn-soybean basal diet (control) or the same basal
      diet supplemented with the following sources of zinc: (i) 100 mg/kg of Zn as
      ZnSO4 ; (ii) 100 mg/kg of Zn as chitosan-Zn chelate (CS-Zn); and (iii) 100 mg/kg
      of Zn as ZnSO4 mixed with chitosan (CS + ZnSO4 ). The results showed that CS-Zn
      could highly improve average daily gain and average daily feed intake than those
      of ZnSO4 or CS+ ZnSO4 (P < 0.05). The pigs fed dietary CS-Zn had lower diarrhea
      incidence and higher apparent digestibility of crude protein than those of the
      pigs fed dietary ZnSO4 (P < 0.05). The protease activities in duodenal content of
      the pigs receiving CS-Zn diets was higher than that of the pigs fed dietary ZnSO4
      or CS + ZnSO4 (P < 0.05). The amylase activity in duodenal content of the pigs
      fed dietary CS-Zn was higher than that of the pigs receiving ZnSO4 diets or basal
      diets (P < 0.05). These results indicated that dietary CS-Zn showed different
      bioactivities from ZnSO4 or CS + ZnSO4 in reducing the incidence of diarrhea,
      improving activities of digestive enzymes and growth performance of weaned pigs.

PMID- 26304727
TI  - Polarized E-cadherin endocytosis directs actomyosin remodeling during embryonic
      wound repair.
AB  - Embryonic epithelia have a remarkable ability to rapidly repair wounds. A
      supracellular actomyosin cable around the wound coordinates cellular movements
      and promotes wound closure. Actomyosin cable formation is accompanied by
      junctional rearrangements at the wound margin. We used in vivo time-lapse
      quantitative microscopy to show that clathrin, dynamin, and the ADP-ribosylation
      factor 6, three components of the endocytic machinery, accumulate around wounds
      in Drosophila melanogaster embryos in a process that requires calcium signaling
      and actomyosin contractility. Blocking endocytosis with pharmacological or
      genetic approaches disrupted wound repair. The defect in wound closure was
      accompanied by impaired removal of E-cadherin from the wound edge and defective
      actomyosin cable assembly. E-cadherin overexpression also resulted in reduced
      actin accumulation around wounds and slower wound closure. Reducing E-cadherin
      levels in embryos in which endocytosis was blocked rescued actin localization to
      the wound margin. Our results demonstrate a central role for endocytosis in wound
      healing and indicate that polarized E-cadherin endocytosis is necessary for
      actomyosin remodeling during embryonic wound repair. 

PMID- 26304730
TI  - Central-Variant Posterior Reversible Encephalopathy due to Sulfasalazine: A Case
      Report.
AB  - OBJECTIVE: To report a rare case with central-variant posterior reversible
      encephalopathy syndrome due to sulfasalazine. CLINICAL PRESENTATION AND
      INTERVENTION: A 55-year-old female patient presented with seizure and acute-onset
      hemiparesia. Thirty days earlier, treatment with sulfasalazine was commenced in
      response to a diagnosis of psoriatic arthritis. Laboratory examinations were
      normal. Brain magnetic resonance imaging showed symmetric edema within basal
      ganglia and thalami with sparing of the cerebral cortices. After stopping the
      treatment of sulfasalazine, clinical and radiological findings regressed
      dramatically. CONCLUSION: This was a case of central-variant posterior reversible
      encephalopathy syndrome due to sulfasalazine, and atypical imaging findings
      should be kept in mind for early diagnosis.

PMID- 26304731
TI  - The biological complexity of urothelial carcinoma: Insights into carcinogenesis,
      targets and biomarkers of response to therapeutic approaches.
AB  - Bladder cancer is a major cause of morbidity, mortality and health-related costs.
      Urothelial carcinoma is by far the most common histologic type of bladder cancer
      and may also arise from the upper urinary tract, e.g. renal pelvis and ureter, as
      well as from the proximal urethra. There have been no major advances in the
      development of new systemic therapies for urothelial carcinoma for over two
      decades, which may be related to prior lack of profound comprehension of
      biological pathogenetic mechanisms. However, in the last few years there has been
      a major shift in the development of new promising therapies that stem from
      improved molecular profiling of this malignancy. Developments in molecular
      biology, genomics, bioinformatics and immunology provide a solid foundation for
      therapeutic advances. A plethora of novel treatment targets and biomarkers are
      being evaluated, but there has been no molecular biomarker with established
      clinical utility so far. Genomic characterization of each patient's tumor has not
      been implemented due to the high cost, lack of validated standardized techniques
      that could be available in different laboratories, as well as absence of
      validated biomarkers and available therapeutic agents with clinically proven
      benefit. However, genomic characterization before treatment has now started to be
      implemented in novel clinical trial designs in order to contribute to proper
      patient selection based on biomarker-based enrichment strategies. Several
      "umbrella" or "basket" type, molecular biomarkers-based trials, in which patient
      eligibility and/or stratification is based on the presence of specific genetic
      alterations regardless of tissue of origin and/or histology, are being launched.
      Mathematical models and bioinformatics platforms that perform high level
      computational integrated pathway analysis may reveal clinical relevant signaling
      pathways amenable for targeting in individual patient tumors. Moreover, the high
      mutational burden of urothelial carcinoma may create numerous neo-antigens that
      may explain the very promising results with immune checkpoint inhibitors in early
      phase clinical trials. A combination of several, e.g. DNA, mRNA, miRNA, protein,
      and other molecular biomarkers merit further investigation, but this process has
      to be based on stringent criteria that test and prove clinical utility. 

PMID- 26304732
TI  - VLP production in Leishmania tarentolae: A novel expression system for
      purification and assembly of HPV16 L1.
AB  - Viral like particles (VLPs) have been used as immunogen for improvement of
      preventive vaccines against several viral infections in preclinical and clinical
      trials. These constructs can stimulate both cellular and humoral immunity. Two
      prophylactic HPV L1 VLP vaccines known as Gardasil and Cervarix were
      commercialized worldwide. However, there are main problems for expression and
      purification of VLPs in eukaryotic expression systems such as baculovirus and
      yeast leading to high cost of these vaccines. A novel Leishmania protozoan system
      has been applied to produce different recombinant proteins due to unique
      properties including generation of similar proteins with mammalian, easy
      handling, and large-scale culture. In the current study, we developed a novel
      strategy to produce HPV L1 VLP using stably transfected Leishmania cells. The
      positive transfectants were analyzed by SDS-PAGE and Western blot analysis. The
      assembly of purified L1 protein was detected by TEM microscopy. Finally, C57BL/6
      mice were immunized by crude VLPs and antibody responses were assessed. The
      results of electronic microscopy revealed average 55-60 nm for L1 VLP.
      Furthermore, high IgG1 and IgG2a antibody responses were generated by L1 VLPs in
      mice similar to L1 VLPs produced in baculovirus-infected insect cells. Regarding
      the results, the amount of recombinant protein generated by Leishmania was 2
      3mg/500 ml media, suggesting further optimization of this system for using in
      large animals and human.

PMID- 26304733
TI  - Fetal Heart Rate Monitoring during Intrauterine Open Surgery for Myelomeningocele
      Repair.
AB  - OBJECTIVE: The aim of this study was to assess fetal hemodynamics during
      intrauterine open surgery for myelomeningocele (MMC) repair by describing fetal
      heart rate (FHR) monitoring in detail related to each part of the procedure.
      METHODS: A study was performed with 57 fetuses submitted to intrauterine MMC
      repair between the 24th and 27th week of gestation. Evaluations of FHR were made
      in specific periods: before anesthesia, after anesthesia, at the beginning of
      laparotomy, during uterus abdominal withdrawal, hysterotomy, neurosurgery (before
      incision, during early skin manipulation, spinal cord releasing, and at the end
      of neurosurgery), abdominal cavity reintroduction, and abdominal closure, and at
      the end of surgery. Means +/- standard deviations of FHR were established for
      each period, and analysis of variance with repeated measures was used to assess
      differences between these periods. The mean differences were assessed with 95%
      confidence intervals and were analyzed by Tukey's multiple comparison test.
      RESULTS: The mean FHR during the specific periods mentioned above was 140.2, 140,
      139.2, 138.8, 135.1, 133.9, 123.1, 134.0, 134.5, 137.9, and 139.9 bpm,
      respectively (p < 0.0001). Comparing the different periods, the highest
      frequencies were observed in the initial and final moments. The neurosurgery
      stage presents lower frequencies, especially during the release of the spinal
      cord. CONCLUSION: FHR monitoring revealed interesting findings in terms of
      physiological fetal changes during MMC repair, especially during neurosurgery,
      which was the most critical period.

PMID- 26304734
TI  - Physician-Rating Web Sites: Ethical Implications.
AB  - PURPOSE: To understand the ethical and professional implications of physician
      behavior changes secondary to online physician-rating Web sites (PRWs). METHODS:
      The American Society for Surgery of the Hand (ASSH) Ethics and Professionalism
      Committee surveyed the ASSH membership regarding PRWs. We sent a 14-item
      questionnaire to 2,664 active ASSH members who practice in both private and
      academic settings in the United States. RESULTS: We received 312 responses, a 12%
      response incidence. More than 65% of the respondents had a slightly or highly
      unfavorable impression of these Web sites. Only 34% of respondents had ever
      updated or created a profile for PRWs, although 62% had observed inaccuracies in
      their profile. Almost 90% of respondents had not made any changes in their
      practice owing to comments or reviews. One-third of respondents had solicited
      favorable reviews from patients, and 3% of respondents have paid to improve their
      ratings. CONCLUSIONS: PRWs are going to become more prevalent, and more research
      is needed to fully understand the implications. There are several ethical
      implications that PRWs pose to practicing physicians. We contend that it is
      morally unsound to pay for good reviews. The recourse for physicians when an
      inaccurate and potentially libelous review has been written is unclear. Some
      physicians have required patients to sign a waiver preventing them from posting
      negative comments online. We propose the development of a task force to assess
      the professional, ethical, and legal implications of PRWs, including working with
      companies to improve accuracy of information, oversight, and feedback
      opportunities. CLINICAL RELEVANCE: It is expected that PRWs will play an
      increasing role in the future; it is unclear whether there will be a uniform
      reporting system, or whether these online ratings will influence referral
      patterns and/or quality improvement.

PMID- 26304735
TI  - The Effect of 1-Ethyl-3-(3-Dimethylaminopropyl) Carbodiimide Suture Coating on
      Tendon Repair Strength and Cell Viability in a Canine Model.
AB  - PURPOSE: To determine if impregnating a suture with a cross-linking agent, 1
      ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC), improved suture
      pull-out strength and cell viability. METHODS: Canine flexor digitorum profundus
      tendons were cut in canine zone D, and a single suture loop was placed in each
      end, with sutures soaked in either saline or an EDC solution with a concentration
      of 1%, 10%, or 50%. Suture pull-out strength, stiffness, and elongation to
      failure was determined by pulling the loop until failure. Cytotoxicity of the EDC
      treatment was evaluated by suspending treated sutures over cultured tenocytes.
      RESULTS: Mechanical properties for the EDC-treated side were improved over
      controls when treated with the 10% and 50% EDC solutions. The ratio of dead to
      live cells was significantly increased at all distances from the suture for the
      50% EDC-treated group. CONCLUSIONS: Suture treated with a 10% EDC solution
      provided the best combination of mechanical reinforcement and limited toxicity.
      CLINICAL RELEVANCE: Sutures so treated may improve the ability of a tendon repair
      to sustain early mobilization.

PMID- 26304736
TI  - Biomechanical Study of the Digital Flexor Tendon Sliding Lengthening Technique.
AB  - PURPOSE: To compare the mechanical properties of sliding lengthening (SL) and Z
      lengthening (ZL) for flexor tendon elongation used for conditions such as
      Volkmann contracture, cerebral palsy, and poststroke spasticity. METHODS: We
      harvested 56 flexor tendons, including flexor pollicis longus tendons, flexor
      digitorum superficialis tendons (zones II to IV), and flexor digitorum profundus
      tendons (zones II to V) from 24 upper limbs of 12 fresh cadavers. Each tendon was
      harvested together with its homonymous tendon from the opposite side of the
      cadaver and paired. We used 28 pairs of tendons and divided them randomly into 4
      groups depending on the lengthening distance (20 or 30 mm) and type of stitching
      (single or double mattress sutures). Then we divided each pair into either the SL
      or ZL group. Each group was composed of 7 specimens. The same surgeon lengthened
      all tendons and stitched them with 2-0 polyester sutures. We tested biomechanical
      tensile strength immediately after completing lengthening and suturing in each
      group. RESULTS: Ultimate tensile strengths were: 23 N for the SL 20-mm
      lengthening and single mattress suture and 7 N for the ZL; 25 N for the SL 20-mm
      lengthening and double mattress suture and 10 N for the ZL; 15 N for the SL 30-mm
      lengthening and single mattress suture and 8 N for the ZL; and 18 N for the SL 30
      mm lengthening and double mattress suture and 10 N for the ZL. CONCLUSIONS: The
      SL technique may be a good alternative to the ZL technique because it provides
      higher ultimate tensile strength. CLINICAL RELEVANCE: Because of its higher
      ultimate tensile strength, the SL technique may allow for earlier rehabilitation
      and reduced risk of postoperative complications.

PMID- 26304737
TI  - The Extended Flexor Carpi Radialis Approach for Concurrent Carpal Tunnel Release
      and Volar Plate Osteosynthesis for Distal Radius Fracture.
AB  - PURPOSE: To determine the relative benefits of an extended flexor carpi radialis
      (FCR) (eFCR) approach with prophylactic carpal tunnel release at the time of
      volar plate osteosynthesis for distal radius fracture via a single incision into
      the traditional volar Henry (VH) approach. METHODS: This was a prospective cohort
      comparison of preoperative and postoperative median nerve function of 27 patients
      (15 eFCR and 12 VH) with unilateral, isolated distal radius fractures requiring
      open reduction internal fixation without preoperative acute carpal tunnel
      syndrome. Patients were operated on via either the eFCR or VH approach. The
      validated Levine-Katz Carpal Tunnel Questionnaire (symptom and functional
      severity scores) was administered and Semmes-Weinstein monofilament and 2-point
      discrimination testing were conducted preoperatively and at 6 weeks and 3 months
      postoperatively. Grip and pinch strength were measured at 6 weeks and 3 months.
      The groups were comparable in terms of age, sex, and fracture type and
      displacement. RESULTS: Comparing across groups, there were no statistically
      significant differences in any outcome measured preoperatively or
      postoperatively. The eFCR and VH groups demonstrated significant improvement in
      functional severity scores, symptom severity, and grip strength. The symptom
      severity score improved to statistical significance at 6 weeks in the eFCR group
      and at 3 months in the VH group. CONCLUSIONS: In this small comparative study,
      the eFCR approach was found to be safe and efficacious. There was no increased
      surgical morbidity, which suggests that this technique can be used safely for all
      patients undergoing volar plating and not just in cases of concurrent carpal
      tunnel syndrome. It allows easier retraction of carpal tunnel contents;
      therefore, it is our preferred approach.

PMID- 26304738
TI  - [Chronic constipation].
AB  - Infant constipation is a common problem in pediatric practice and it constitutes
      approximately 25% of children's gastroenterologist consultations. An average
      prevalence of 8.9% in the pediatric population is described, but it varies as it
      is influenced by different dietary habits and definitions used in the studied
      populations. 90 to 95% of the cases have a functional cause, where the most
      important therapeutic measures are: Education to children and their parents,
      forming a stool pattern, a diet rich in fiber and the use of drugs for
      disimpaction treatment and maintenance. Finally, it is important to explain to
      parents that the treatment is usually long, due to frequent relapses. It is
      described that 25% of affected children will continue with symptoms into
      adulthood. 

PMID- 26304739
TI  - Acoustic metamaterial for subwavelength edge detection.
AB  - Metamaterials have demonstrated the possibility to produce super-resolved images
      by restoring propagative and evanescent waves. However, for efficient information
      transfer, for example, in compressed sensing, it is often desirable to visualize
      only the fast spatial variations of the wave field (carried by evanescent waves),
      as the one created by edges or small details. Image processing edge detection
      algorithms perform such operation, but they add time and complexity to the
      imaging process. Here we present an acoustic metamaterial that transmits only
      components of the acoustic field that are approximately equal to or smaller than
      the operating wavelength. The metamaterial converts evanescent waves into
      propagative waves exciting trapped resonances, and it uses periodicity to
      attenuate the propagative components. This approach achieves resolutions ~5 times
      smaller than the operating wavelength and makes it possible to visualize
      independently edges aligned along different directions. 

PMID- 26304741
TI  - Sex correlates with differences in long-term outcome in chronic myeloid leukaemia
      patients treated with imatinib.

PMID- 26304740
TI  - Transcription errors induce proteotoxic stress and shorten cellular lifespan.
AB  - Transcription errors occur in all living cells; however, it is unknown how these
      errors affect cellular health. To answer this question, we monitor yeast cells
      that are genetically engineered to display error-prone transcription. We discover
      that these cells suffer from a profound loss in proteostasis, which sensitizes
      them to the expression of genes that are associated with protein-folding diseases
      in humans; thus, transcription errors represent a new molecular mechanism by
      which cells can acquire disease phenotypes. We further find that the error rate
      of transcription increases as cells age, suggesting that transcription errors
      affect proteostasis particularly in aging cells. Accordingly, transcription
      errors accelerate the aggregation of a peptide that is implicated in Alzheimer's
      disease, and shorten the lifespan of cells. These experiments reveal a previously
      unappreciated role for transcriptional fidelity in cellular health and aging. 

PMID- 26304742
TI  - Structures, Hydration, and Electrical Mobilities of Bisulfate Ion-Sulfuric Acid
      Ammonia/Dimethylamine Clusters: A Computational Study.
AB  - Despite the well-established role of small molecular clusters in the very first
      steps of atmospheric particle formation, their thermochemical data are still not
      completely available due to limitation of the experimental techniques to treat
      such small clusters. We have investigated the structures and the thermochemistry
      of stepwise hydration of clusters containing one bisulfate ion, sulfuric acid,
      base (ammonia or dimethylamine), and water molecules using quantum chemical
      methods. We found that water facilitates proton transfer from sulfuric acid or
      the bisulfate ion to the base or water molecules, and depending on the hydration
      level, the sulfate ion was formed in most of the base-containing clusters. The
      calculated hydration energies indicate that water binds more strongly to ammonia
      containing clusters than to dimethylamine-containing and base-free clusters,
      which results in a wider hydrate distribution for ammonia-containing clusters.
      The electrical mobilities of all clusters were calculated using a particle
      dynamics model. The results indicate that the effect of humidity is negligible on
      the electrical mobilities of molecular clusters formed in the very first steps of
      atmospheric particle formation. The combination of the results of this study with
      those previously published on the hydration of neutral clusters by our group
      provides a comprehensive set of thermochemical data on neutral and negatively
      charged clusters containing sulfuric acid, ammonia, or dimethylamine. 

PMID- 26304743
TI  - Second allogeneic stem cell transplant for aplastic anaemia: a retrospective
      study by the Severe Aplastic Anaemia Working Party of the European Society for
      Blood and Marrow Transplantation.
AB  - We analysed the outcome of a second allogeneic haematopoietic stem cell
      transplant (alloHSCT) in 162 patients reported to the European Society for Blood
      and Marrow Transplantation between 1998 and 2009. Donor origin was a sibling in
      110 and an unrelated donor in 52 transplants, respectively. The stem cell source
      was bone marrow in 31% and peripheral blood in 69% of transplants. The same donor
      as for the first alloHSCT was used in 81% of transplants whereas a change in the
      choice of stem cell source was reported in 56% of patients, mainly from bone
      marrow to peripheral blood. Neutrophil and platelet engraftment occurred in 85%
      and 72% of patients, after a median time of 15 and 17 days, respectively. Grade
      II-IV acute graft-versus-host disease (GVHD) and chronic GVHD occurred in 21% and
      37% of patients, respectively. Graft failure (GF) occurred in 42 patients (26%).
      After a median follow-up of 3.5 years, the 5-year overall survival (OS) was
      60.7%. In multivariate analysis, the only factor significantly associated with a
      better outcome was a Karnofsky/Lansky score >=80 (higher OS). We conclude that a
      second alloHSCT is feasible rescue option for GF in SAA, with a successful
      outcome in 60% of cases. 

PMID- 26304746
TI  - Quantum Interference Effects Theoretically Found in the Photodissociation
      Processes of the Second Absorption Bands of ICl and IBr Molecules.
AB  - Some quantum interference effects are exposed directly in experiments, but others
      are not and remain just hidden and thus require thorough theoretical analysis to
      be exposed. In this respect, the second absorption bands of IX (X = Cl, Br)
      molecules show an interesting behavior in the photofragment anisotropy of the
      lowest I((2)P3/2)+X((2)P3/2) product channel; it changes from strongly parallel
      distribution on the shorter wavelength side to strongly perpendicular
      distribution on the longer wavelength side. Because the responsible perpendicular
      third Omega = 1 (1(III)) excited state correlating adiabatically to this product
      channel has only a weak absorption, the parallel component flux yielding the same
      products must be comparatively weak, even though the responsible parallel
      excitations to the 0(+)(III) and/or 0(+)(IV) excited states have strong
      absorptions. In the present theoretical study, the branching ratios and the
      anisotropy parameters have been obtained using the spin-orbit configuration
      interaction method combined with the quantum mechanical wavepacket and
      semiclassical approaches. Significant quantum interference effect between the two
      dissociative de Broglie waves on the 0(+)(III) and 0(+)(IV) potential curves has
      been found through the avoided crossing, and the weak parallel flux to the ground
      state product channel has been explained by their destructive interference
      character. This interference effect has weak excitation energy dependence due to
      rather unique behavior of their almost parallel potential curves from the Franck
      Condon to avoided crossing regions. 

PMID- 26304745
TI  - Bluetongue in small ruminants: An opinionated review, with a brief appraisal of
      the 2014 outbreak of the disease in Greece and the south-east Europe.
AB  - Bluetongue is an arthropod-borne viral disease of ruminants, especially of sheep,
      caused by Bluetongue virus, which belongs to the genus Orbivirus of the family
      Reoviridae and is classified into 26 antigenically distinct serotypes. Once
      thought to be restricted in Africa and parts of the Middle East, bluetongue has
      now become a concern in sheep-rearing countries around the world. In the past 10
      years, severe outbreaks have occurred in Europe with important economic
      consequences; of these, the 2006-20008 outbreak in Europe was caused by a
      serotype 8 strain and the 2014 outbreak in Greece and the other countries of
      south-east Europe was caused by a serotype 4 strain, suggested to be a
      reassortant strain with genome segments from lineages of serotype 1, 2 and 4.
      Immunisation campaigns can be implemented for successful control and limiting of
      the disease. Nevertheless, in both of the above outbreaks, late application of
      vaccinations led to a wide spread of the disease, which subsequently resulted in
      significant losses in livestock in the affected regions. In view of that,
      standardisation of control measures in the future will be beneficial for
      efficiently limiting outbreaks of the disease. 

PMID- 26304747
TI  - Indirect induction of regulatory T cells accompanies immune responses during
      peptide vaccination of chronic lymphocytic leukaemia patients.

PMID- 26304750
TI  - Structure of nucleoli in first-order spermatocytes of selected free-living animal
      species.
AB  - Nucleoli are the product of the activity of nucleolar organizer regions (NOR) in
      certain chromosomes. Their main functions are the formation of ribosomal subunits
      from ribosomal protein molecules and the transcription of genes encoding rRNA.
      Nucleoli are present in the nuclei of nearly all eukaryotic cells because they
      contain housekeeping genes. The size and number of nucleoli gradually decrease
      during spermatogenesis. Some of the material originating in the nucleolus
      probably migrates to the cytoplasm and takes part in the formation of chromatoid
      bodies (CB). Nucleolus fragmentation and CB assembly take place at the same stage
      of spermatogenesis. CB are involved in the formation of the acrosome, the
      migration of mitochondria to the midpiece, and the formation of the sperm tail
      fibrous sheath. The aim of the study was to characterize the nucleoli in the
      early prophase of spermatogenesis in the wild boar and the roe deer. The roe deer
      cells have larger nucleoli and a larger cell nucleus than the wild boar cells.
      The area of the nucleolus as a percentage of the total area of the nucleus was
      larger as well. The coefficients of variation for all parameters were higher in
      the roe deer. In the wild boar cells the nucleoli were mainly regularly shaped.
      The size of the nucleolus and the nucleus of the spermatocyte is a species
      specific trait associated with karyotype and the number of nucleolar organizer
      regions in a given species. 

PMID- 26304749
TI  - HCRP-1 regulates cell migration and invasion via EGFR-ERK mediated up-regulation
      of MMP-2 with prognostic significance in human renal cell carcinoma.
AB  - Previous studies indicated a role of hepatocellular carcinoma-related protein
      1(HCRP-1) in human cancers, however, its expression pattern in renal cell
      carcinoma (RCC) and the molecular mechanism of HCRP-1 on cancer progression have
      not been characterized. In the present study, HCRP-1 expression was examined in a
      RCC tissue microarray. The negative expression of HCRP-1 was significantly
      correlated with tumor grade (P = 0.002), TNM stage (P = 0.001) and pT status (P =
      0.003). Furthermore, we showed a strong correlation between negative HCRP-1
      expression and worse overall and disease-specific survival (P = 0.0003 and P =
      0.0012, respectively). Knockdown of HCRP-1 promoted cell migration and invasion
      in 786-O and OS-RC-2 cell lines. HCRP-1 depletion increased matrix
      metalloproteinase (MMP)-2 protein level, with increased extracellular signal
      regulatedkinase (ERK) phosphorylation, which could be reversed by ERK siRNA or
      ERK inhibitor, PD98059. Further analysis showed that HCRP-1 knockdown induced
      epidermal growth factor receptor (EGFR) phosphorylation. Treatment with EGFR
      inhibitor or EGFR siRNA blocked HCRP-1-mediated up-regulation of EGFR, ERK
      phosphorylation and MMP-2 expression. In summary, our results showed that
      negative HCRP-1 expression is an independent prognostic factor for RCC patients
      and promotes migration and invasion by EGFR-ERK-mediated up-regulation of MMP-2.
      HCRP-1 may serve as a therapeutic target for RCC. 

PMID- 26304751
TI  - Long-term in vitro culture of bovine preantral follicles: Effect of base medium
      and medium replacement methods.
AB  - Two culture media and replacement methods were compared during long-term in vitro
      culture of secondary follicles of cattle using alpha-MEM(+) or TCM-199(+) as base
      media. The medium replacement methods were: Conventional - removal and subsequent
      addition of the same amount (60MUl) in a 100MUl aliquot (MEM-C and TCM-C), and
      Small Supplementation - addition of 5MUl of fresh medium to an initial small
      aliquot (50MUl), resulting in a final volume of 125MUl on the last day of culture
      (MEM-S and TCM-S). A total of 207 secondary follicles were cultured individually
      for 32 days at 38.5 degrees C in 5% CO2 and medium replacement was performed
      every other day. The MEM-S treatment resulted in a larger (P<0.01) follicular
      diameter, greater (P<0.02) growth rate, greater (P<0.02) antrum formation, as
      well as greater (P<0.0001) estradiol concentrations when compared with the MEM-C
      treatment. The medium change methods did not affect (P>0.05) the follicular and
      estradiol end points for TCM-199(+). The expression of the FSHR gene was greater
      (P<0.03) with the TCM-C than TCM-S treatment, while the relative amounts of mRNA
      for IGF1 was greater (P<0.02) with MEM-S than TCM-S treatments and for VEGF was
      greater (P<0.02) with MEM-C than TCM-C treatment. In conclusion, the type of base
      medium and the effect of periodic addition of medium differentially affected
      follicle development, estradiol production, and gene expression. Furthermore,
      alpha-MEM(+) can be used to replace TCM-199(+) for culture of preantral follicles
      of cattle if progressive addition of medium is used for medium change. 

PMID- 26304754
TI  - Bone morphogenetic protein-4 and 7 and receptors regulate vascular endothelial
      growth factor and receptors in human fetal leptomeninges.
AB  - Bone morphogenetic proteins (BMP) 4 and 7 have important roles in neuronal
      differentiation and cortical development in the murine brain. However BMP4 and
      BMP7 expression and functions in the developing human brain are unknown. In this
      study, frozen tissue human fetal leptomeninges, formalin-fixed tissue and primary
      fetal leptomeningeal cell cultures were studied. By western blot, BMP4, BMP7 and
      BMPRIa were demonstrated in 15, 17 20, 23 week (wk) human leptomeninges. BMP
      receptor II was detected at 15 and 17 wks. Immunohistochemically, BMP4
      immunoreactivity was also found in 20 to 39 wk human leptomeninges. BMP4
      significantly reduced basal DNA synthesis at 22 wks. BMP7 100 and 300 ng/ml
      stimulated basal DNA synthesis in the 15, 17 and 22 wk leptomeninges. BMP4 and
      BMP7 increased phosphorylation of SMAD-1, 5, 8 in most cells and had no effect on
      phosphorylation of p-38MAPK, or p44/42MAPK. BMP4 and BMP7 produced a decrease in
      VEGF RNA expression in 2 of 4 leptomeninges. BMP4 and BMP7 increased VEGFR1 RNA
      in 2 or 3 of 4 leptomeningeal cultures respectively. BMP4 produced a decrease in
      VEGFR2 RNA in 2 of 4 and BMP7 in 3 of 4 while BMP7 reduced VEGFR2 protein in the
      leptomeninges. The findings show, for the first time, BMP4, BMP7 and receptors
      are expressed and active in the human fetal leptomeninges. They suggest these
      BMPs influence vascular development in this tissue by regulating VEGF and its
      receptors.

PMID- 26304753
TI  - Role of phosphatase activity of soluble epoxide hydrolase in regulating
      simvastatin-activated endothelial nitric oxide synthase.
AB  - Soluble epoxide hydrolase (sEH) has C-terminal epoxide hydrolase and N-terminal
      lipid phosphatase activity. Its hydrolase activity is associated with endothelial
      nitric oxide synthase (eNOS) dysfunction. However, little is known about the role
      of sEH phosphatase in regulating eNOS activity. Simvastatin, a clinical lipid
      lowering drug, also has a pleiotropic effect on eNOS activation. However, whether
      sEH phosphatase is involved in simvastatin-activated eNOS activity remains
      elusive. We investigated the role of sEH phosphatase activity in simvastatin
      mediated activation of eNOS in endothelial cells (ECs). Simvastain increased the
      phosphatase activity of sEH, which was diminished by pharmacological inhibitors
      of sEH phosphatase. In addition, pharmacological inhibition of sEH phosphatase or
      overexpressing the inactive phosphatase domain of sEH enhanced simvastatin
      induced NO bioavailability, tube formation and phosphorylation of eNOS, Akt, and
      AMP-activated protein kinase (AMPK). In contrast, overexpressing the phosphatase
      domain of sEH limited the simvastatin-increased NO biosynthesis and eNOS
      phosphorylation at Ser1179. Simvastatin evoked epidermal growth factor receptor-c
      Src-increased Tyr phosphorylation of sEH and formation of an sEH-Akt-AMPK-eNOS
      complex, which was abolished by the c-Src kinase inhibitor PP1 or c-Src dominant
      negative mutant K298M. These findings suggest that sEH phosphatase activity
      negatively regulates simvastatin-activated eNOS by impeding the Akt-AMPK-eNOS
      signaling cascade. 

PMID- 26304756
TI  - Peristeen((r)) transanal irrigation in paediatric patients with anorectal
      malformations and spinal cord lesions: a multicentre Italian study.
AB  - AIM: In paediatric and adult patients with neurogenic bowel, transanal irrigation
      (TAI) of the colon has gained popularity due to the introduction of a
      specifically designed device. The aim of this pilot study was to present the
      results of TAI using the Peristeen((r)) TAI system in a group of paediatric
      patients with anorectal malformation (ARM) and congenital or acquired spinal cord
      lesions (SCLs). METHOD: Eight Italian paediatric surgery and spina bifida centres
      participated in the study. The inclusion criteria were age between 6 and 17
      years, weight above 20 kg and unsatisfactory bowel management. Patients with
      chronic inflammatory bowel disease, mental disability and surgery within the
      previous 3 months were excluded. At the beginning of treatment (T0) and after 3
      months (T1) the Bristol scale, a questionnaire assessing bowel function, and two
      questionnaires on quality of life (QoL) for patients aged 6-11 years (CHQ-pf50)
      and 12-17 years (SF36) were administered. RESULTS: Eighty-three patients were
      enrolled, and seventy-eight completed the study (41 ARMs, 37 SCLs). At T1,
      constipation was reduced in ARMs from 69% to 25.6% and in SCLs from 92.7% to
      41.5%, faecal incontinence in ARMs from 50% to 18.6% and in SCLs from 39% to 9.8%
      and flatus incontinence in ARMs from 20.9% to 9.8% and in SCLs from 31.7% to 10%.
      At T0, the Bristol Stool Scale types were 1-2 in 45% of ARMs and 77.5% of SCL
      patients, whereas at T1 types 1-2 were recorded in only 2.5% of SCL patients. QoL
      improved in both groups. In the younger group, a significant improvement in QoL
      was recorded in ARM patients for eight of nine variables and in SCL patients for
      seven of nine variables. CONCLUSION: This study showed that Peristeen TAI
      resulted in a significant time reduction in colonic cleansing, increased
      independence from the carer and improved QoL in paediatric patients with ARMs and
      SCLs.

PMID- 26304757
TI  - Suicide by blunt head trauma - Two cases with striking similarities.
AB  - There have been several forensic pathological studies on the distinction between
      falls from height and homicidal blows in blunt head trauma, but few studies have
      focused on suicidal blows. Self-inflicted blunt head trauma is usually a part of
      a complex suicide with more than one suicidal method applied. Actually, no
      reports on suicide indicate blunt head trauma to be the singular cause of death
      in recent publications. Cases with self-inflicted blunt trauma are often
      challenging for those involved in the investigation because they are confronted
      with findings that are also found in homicides. A refined guideline to
      differentiate suicidal blows from homicidal blows in blunt head trauma allows for
      a more accurate representation of the events surrounding death. This paper
      presents two cases of suicide by self-inflicted blunt head trauma in which blunt
      head trauma from repeatedly hitting the decedent's head with a hammer was
      considered to be the only cause of death. 

PMID- 26304758
TI  - Segmental distribution of the motor neuron columns that supply the rat hindlimb:
      A muscle/motor neuron tract-tracing analysis targeting the motor end plates.
AB  - Spinal cord injury (SCI) that disrupts input from higher brain centers to the
      lumbar region of the spinal cord results in paraplegia, one of the most
      debilitating conditions affecting locomotion. Non-human primates have long been
      considered to be the most appropriate animal to model lower limb dysfunction.
      More recently, however, there has been a wealth of scientific information
      gathered in the rat regarding the central control of locomotion. Moreover, rodent
      models of SCI at lumbar levels have been widely used to validate therapeutic
      scenarios aimed at the restoration of locomotor activities. Despite the growing
      use of the rat as a model of locomotor dysfunction, knowledge regarding the
      anatomical relationship between spinal cord motor neurons and the hindlimb
      muscles that they innervate is incomplete. Previous studies performed in our
      laboratory have shown the details of the muscle/motor neuron topographical
      relationship for the mouse forelimb and hindlimb as well as for the rat forelimb.
      The present analysis aims to characterize the segmental distribution of the motor
      neuron pools that innervate the muscles of the rat hindlimb, hence completing
      this series of studies. The location of the motor end plate (MEP) regions on the
      main muscles of the rat hindlimb was first revealed with acetylcholinesterase
      histochemistry. For each muscle under scrutiny, injections of Fluoro-Gold were
      then performed along the length of the MEP region. Targeting the MEPs gave rise
      to columns of motor neurons that span more spinal cord segments than previously
      reported. The importance of this study is discussed in terms of its application
      to gene therapy for SCI. 

PMID- 26304759
TI  - Facial rejuvenation starts in the midface: three-dimensional volumetric facial
      rejuvenation has beneficial effects on nontreated neighboring esthetic units.
AB  - Facial aging is a major indication for minimal invasive esthetic procedures.
      Dermal fillers are a cornerstone in the approach for facial sculpturing. But
      where to start? Our concept is midfacial volume restoration in first place. This
      will result in a healthy and youthful appearance creating a facial V-shape. But
      midfacial filler injection does not only improve the malar area. It has also
      beneficial effects on neighboring esthetic units. We report on such improvements
      in periocular and nasolabial region, upper lips and perioral tissue, and the jaw
      line and discuss anatomical background. We hypothesize that midfacial deep filler
      injections also may activate subdermal white adipose tissue stem cells
      contributing to longer lasting rejuvenation. 

PMID- 26304760
TI  - Nonlinear feature extraction for objective classification of complex auditory
      brainstem responses to diotic perceptually critical consonant-vowel syllables.
AB  - OBJECTIVE: To examine if nonlinear feature extraction method yields appropriate
      results in complex brainstem response classification of three different consonant
      vowels diotically presented in normal Persian speaking adults. METHODS: Speech
      evoked auditory brainstem responses were obtained in 27 normal hearing young
      adults by using G.tec EEG recording system. 170ms synthetic consonant-vowel
      stimuli /ba/, /da/, /ga/ were presented binaurally and the recurrence
      quantification analysis was performed on the responses. The recurrence time of
      second type was proposed as a suitable feature. ANOVA was also used for testing
      the significance of extracted feature. Post-comparison statistical method was
      used for showing which means are significantly different from each other.
      RESULTS: Dimension embedding and state space reconstruction were helpful for
      visualizing nonlinearity in auditory system. The proposed feature was successful
      in the objective classification of responses in window time 20.1-35.3ms, which
      belonged to formant transition period of stimuli. Also the p value behavior of
      recurrence time of second type feature as a discriminant feature was close to the
      nature of the response that includes transient and sustained parts. On the other
      hand, the /ba/ and /ga/ classification period was wider than the others.
      CONCLUSION: The extracted feature shown in this paper is helpful for the
      objective of distinguishing individuals with auditory processing disorders in the
      structurally similar voices. On the other hand, differing nonlinear feature is
      meaningful in a special region of response, equal to formant transition period,
      and this feature is related to the state space changes of brainstem response. It
      can be assumed that more information is within this region of signal and it is a
      sign of processing role of brainstem. The state changes of system are dependent
      on input stimuli, so the existence of top down feedback from cortex to brainstem
      forces the system to act differently.

PMID- 26304762
TI  - Successful Treatment of Recalcitrant Prurigo with Alitretinoin.
AB  - BACKGROUND: Chronic itch with secondary scratch lesions such as prurigo has a
      major impact on quality of life. Due to its relapsing nature and often unknown
      origin, its treatment is challenging. OBJECTIVE: We sought to demonstrate that
      alitretinoin can be an efficacious and well-tolerated treatment in a patient
      suffering from chronic itch with concomitant prurigo and psoriatic lesions.
      METHODS: Case report. RESULTS: After 1 month of alitretinoin treatment (30 mg
      daily), itch as well as prurigo and psoriasis lesions decreased markedly. Three
      cycles of alitretinoin were administered, as each cessation of treatment led to
      relapse of the symptoms after 6-8 weeks. Tapering of the alitretinoin dose (30 mg
      every second day) after the third cycle allowed to maintain the effects for over
      18 months. CONCLUSION: Treatment of refractory prurigo with alitretinoin might be
      an efficacious alternative to standard therapies. In case of relapse, retreatment
      with alitretinoin reinduces a further long-lasting response.

PMID- 26304761
TI  - Increased intravenous morphine self-administration following Roux-en-Y gastric
      bypass in dietary obese rats.
AB  - Roux-en-Y gastric bypass (RYGB) surgery is a commonly performed and very
      effective method to achieve significant, long-term weight loss. Opioid analgesics
      are primarily used to manage postoperative pain as fewer alternative medication
      options are available for bariatric surgery patients than for the general
      population. Recent clinical studies support a greater risk for substance use
      following bariatric surgery, including an increased use of opioid medications.
      The present study is the first to study morphine self-administration in a rat
      model of RYGB. High fat diet-induced obese (HFD-DIO) rats underwent RYGB (n=14)
      or sham-surgery with ad libitum HFD (SHAM, n=14) or a restricted amount that
      resulted in weight matched to the RYGB cohort (SHAM-WM, n=8). An additional
      normal-diet (ND, n=7), intact (no surgery) group of rats was included. Two months
      after the surgeries, rats were fitted with jugular catheters and trained on a
      fixed ratio-2 lick task to obtain morphine intravenously. Both morphine-seeking
      (number of licks on an empty spout to obtain morphine infusion) and consumption
      (number of infusion) were significantly greater in RYGB than any control group
      beginning on day 3 and reached a two-fold increase over a period of two weeks.
      These findings demonstrate that RYGB increases motivation for taking morphine and
      that this effect is independent of weight loss. Further research is warranted to
      reveal the underlying mechanisms and to determine whether increased morphine use
      represents a risk for opioid addiction following RYGB. Identifying risk factors
      preoperatively could help with personalized postoperative care to prevent opioid
      abuse and addiction.

PMID- 26304763
TI  - Clinical and molecular genetic analysis of a family with late-onset LAMA2-related
      muscular dystrophy.
AB  - PURPOSE: LAMA2-related muscular dystrophy (LAMA2 MD) is an autosomal recessive
      inherited disease caused by LAMA2 gene mutation. The spectrum of the phenotype is
      expanding in recent years partially due to the definitive diagnosis of molecular
      genetics. We investigated the phenotype and genotype in a LAMA2 MD family
      manifesting as limb-girdle muscular dystrophy (LGMD). METHODS: The clinical
      information of the proband and his family was collected. Muscle biopsy and
      immunohistochemical staining for the muscle specimen were performed. The genomic
      DNA of the family was extracted from the peripheral blood, and genetic testing
      was analyzed using the next generation sequencing and multiplex ligation
      dependent probe amplification (MLPA). The point mutation was verified by Sanger
      sequencing while exonic deletion was verified by array comparative genomic
      hybridization. RESULTS: The patient had mild motor retardation when he was young,
      and no obvious weakness was reported. Muscle biopsy showed mild atrophy in
      histochemical staining. Immunohistochemical staining using antibody against
      merosin showed nearly normal expression surrounding the muscle fiber. The
      proband's sister had similar symptoms. By analyzing the gene test we found that
      compound heterozygous LAMA2 mutation inherited from the parents respectively. One
      coming from the father was a gross deletion expanding from exon 36 to exon 65.
      The other from the mother was a missense mutation c.1358G>C (p.Cys453Ser). Sanger
      sequencing verified the point mutation. Array comparative genomic hybridization
      confirmed a long stretch of deletion about 27.6-34.7 kb. The sister had the same
      mutations as the proband. We diagnosed the first late onset LAMA2 MD Chinese
      patients on molecular level and genetic counseling is available. CONCLUSION: We
      investigated the phenotype and genotype in a family manifesting as limb-girdle
      muscular dystrophy (LGMD). This LAMA2 MD family manifesting as LGMD was
      identified in molecular genetic level and their phenotypes was described.

PMID- 26304764
TI  - Revisited anti-inflammatory activity of matricine in vitro: Comparison with
      chamazulene.
AB  - The proazulene matricine (1) is present in chamomile flower heads and has been
      proven to exhibit strong in vivo anti-inflammatory activity. In contrast to other
      secondary metabolites in chamomile preparations like its degradation product
      chamazulene (2), no plausible targets have been found to explain this activity.
      Therefore we revisited 1 regarding its in vitro anti-inflammatory activity in
      cellular and molecular studies. Using ICAM-1 as a marker for NF-kappaB
      activation, it was shown that ICAM-1 protein expression induced by TNF-alpha and
      LPS, but not by IFN-gamma, was remarkably inhibited by 1 in endothelial cells
      (HMEC-1). Inhibition was concentration-dependent in a micromolar range (10-75
      MUM) and did not involve cytotoxic effects. At 75 MUM expression of the adhesion
      molecule ICAM-1 was down to 52.7 +/- 3.3% and 20.4 +/- 1.8% of control in TNF
      alpha and LPS-stimulated HMEC-1, respectively. In contrast, 2 showed no activity.
      Quantitative RT-PCR experiments revealed that TNF-alpha-induced expression of the
      ICAM-1 gene was also reduced by 1 in a concentration-dependent manner, reaching
      32.3 +/- 6.2% of control at 100 MUM matricine. Additional functional assays (NF
      kappaB promotor activity and cytoplasm to nucleus translocation) confirmed the
      inhibitory effect of 1 on NF-kappaB signaling. Despite the fact that 1 lacks an
      alpha,beta-unsaturated carbonyl and is thus not able to act via a Michael
      reaction with electron rich SH groups of functional biological molecules, data
      gave strong evidence that 1 inhibits NF-kappaB transcriptional activity in
      endothelial cells by an hitherto unknown mechanism and this may contribute to its
      well-known anti-inflammatory activity in vivo.

PMID- 26304765
TI  - Anti-neuroinflammatory sesquiterpenes from Chinese eaglewood.
AB  - Nine new sesquiterpenes (1-9), together with seventeen known ones (10-26), were
      isolated from Chinese eaglewood. Their structures were established by extensive
      spectroscopic analysis, and the absolute configuration of 6 was determined by the
      modified Mosher's method. Compounds 7, 10, 14, 15, and 21 exhibited significant
      inhibition of nitric oxide production in lipopolysaccharide-stimulated BV-2
      microglial cells with IC50 values in the range 7.1-53.8 MUM.

PMID- 26304766
TI  - Theoretical study of the reactions of Criegee intermediates with ozone,
      alkylhydroperoxides, and carbon monoxide.
AB  - The reaction of Criegee intermediates (CI) with ozone, O3, has been re-examined
      with higher levels of theory, following earlier reports that O3 could be a
      relevant sink of CI. The updated rate coefficients indicate that the reaction is
      somewhat slower than originally anticipated, and is not expected to play a role
      in the troposphere. In experimental (laboratory) conditions, the CI + O3 reaction
      can be important. The reaction of CI with ROOH intermediates is found to proceed
      through a pre-reactive complex, and the insertion process allows for the
      formation of oligomers in agreement with recent experimental observations. The CI
      + ROOH reaction also allows for the formation of ether oxides, which don't react
      with H2O but can oxidize SO2. Under tropospheric conditions, the ether oxides are
      expected to re-dissociate to the CI + ROOH complex, and ultimately follow the
      insertion reaction forming a longer-chain hydroperoxide. The CI + ROOH reaction
      is not expected to play a significant role in the atmosphere. The reaction of CI
      with CO molecules was studied at very high levels of theory, but no energetically
      viable route was found, leading to very low rate coefficients. These results are
      compared against an extensive literature overview of experimental data. 

PMID- 26304767
TI  - Correlation of Subjective Effects with Systemic Opioid Exposure from Fixed-Dose
      Combinations of Oxycodone/Acetaminophen in Recreational Users of Prescription
      Drugs.
AB  - OBJECTIVE: To correlate abuse-related pharmacodynamic measures and
      pharmacokinetic measures after administering immediate-release/extended-release
      and immediate-release oxycodone/acetaminophen fixed-dose combination
      analgesicsDesign. Randomized, double-blind, active- and placebo-controlled, 7-way
      crossover studySetting. Contract research organizationSubjects. Nondependent
      recreational users of prescription opioids. METHODS: Participants received single
      doses of intact immediate-release/extended-release and immediate-release
      oxycodone/acetaminophen 15/650 mg, intact immediate-release/extended-release and
      immediate-release oxycodone/acetaminophen 30/1,300 mg, crushed immediate
      release/extended-release and immediate-release oxycodone/acetaminophen 30/1,300
      mg, and placebo. Measures of pharmacodynamics (pupillometry, drug liking, drug
      high, good drug effects) and pharmacokinetics were assessed predose and up to 24
      hours postdose, and correlations between pharmacokinetic parameters and
      pharmacodynamic data were explored. RESULTS: Of 61 participants, 55 completed all
      7 treatments. Intact immediate-release/extended-release oxycodone/acetaminophen
      produced 50% lower oxycodone peak plasma concentration (Cmax) than immediate
      release oxycodone/acetaminophen. Median oxycodone time to Cmax (tmax) was
      significantly longer (P<0.001) for intact immediate-release/extended-release
      oxycodone/acetaminophen than immediate-release oxycodone/acetaminophen. The
      pharmacokinetics of crushed immediate-release/extended-release and immediate
      release oxycodone/acetaminophen (30/1,300 mg) followed a similar pattern.
      Crushing did not shorten the median oxycodone tmax for immediate-release/extended
      release oxycodone/acetaminophen (30/1,300 mg). Strong correlations were observed
      between oxycodone Cmax and area under the curve from time 0 to time x peak
      effects and area under the subjective effect curve from time 0 to time x for all
      subjective effects (R2=0.711-0.997). CONCLUSION: Immediate-release/extended
      release oxycodone/acetaminophen produced lower oxycodone Cmax and longer tmax
      than immediate-release oxycodone/acetaminophen. Lower oxycodone concentrations,
      particularly at earlier time points, were strongly correlated with lesser
      positive subjective drug effects.

PMID- 26304768
TI  - Stereoselective coordination: a six-membered P,N-chelate tailored for asymmetric
      allylic alkylation.
AB  - Six-membered chelate complexes [Pd(1a-b)Cl2], (2a-b) and [Pd(1a-b)(eta(3)
      PhCHCHCHPh)]BF4, (3a-b) of P,N-type ligands 1a, ((2S,4S)-2-diphenyl-phosphino-4
      isopropylamino-pentane) and 1b, ((2S,4S)-2-diphenyl-phosphino-4-methylamino
      pentane) have been prepared. The Pd-complexes have been characterized in solution
      by 1D and 2D NMR spectroscopy. The observed structures were confirmed by DFT
      calculations and in the case of 2a also by X-ray crystallography. Unexpectedly,
      the coordination of the all-carbon-backbone aminophosphine 1a resulted in not
      only a stereospecific locking of the donor nitrogen atom into one of the two
      possible configurations but also the conformation of the six-membered chelate
      rings containing three alkyl substituents was forced into the same single chair
      structure showing the axially placed isopropyl group on the coordinated N-atom.
      The stereodiscriminative complexation of 1a led to the formation of a palladium
      catalyst with a conformationally rigid chelate having a configurationally fixed
      nitrogen and electronically different coordination sites due to the presence of P
      and N donors. The stereochemically fixed catalyst provided excellent ee's (up to
      96%) and activities in asymmetric allylic alkylation reactions. In contrast, the
      chelate rings formed by 1b exist in two different chair conformations, both
      containing axial methyl groups, but with the opposite configurations of the
      coordinated N-atom. Pd-complexes of 1b provided low enantioselectivities in
      similar alkylations, therefore emphasizing the importance of the stereoselective
      coordination of N-atoms in analogous P-N chelates. The factors determining the
      coordination of the ligands were also studied with respect to the chelate ring
      conformation and the nitrogen configuration.

PMID- 26304769
TI  - Flow tube studies of the C((3)P) reactions with ethylene and propylene.
AB  - Product detection studies of C((3)P) atom reactions with ethylene, C2H4(X(1)Ag)
      and propylene, C3H6(X(1)A') are carried out in a flow tube reactor at 332 K and 4
      Torr (553.3 Pa) under multiple collision conditions. Ground state carbon atoms
      are generated by 193 nm laser photolysis of carbon suboxide, C3O2 in a buffer of
      helium. Thermalized reaction products are detected using tunable VUV
      photoionization and time of flight mass spectrometry. For C((3)P) + ethylene,
      propargyl (C3H3) is detected as the only molecular product in agreement with
      previous studies on this reaction. The temporal profiles of the detected ions are
      used to discriminate C((3)P) reaction products from side reaction products. For
      C((3)P) + propylene, two reaction channels are identified through the detection
      of methyl (CH3) and propargyl (C3H3) radicals for the first channel and C4H5 for
      the second one. Franck-Condon Factor simulations are employed to infer the C4H5
      isomer distribution. The measured 1 : 4 ratio for the i-C4H5 isomer relative to
      the methylpropargyl isomers is similar to the C4H5 isomer distribution observed
      in low-pressure flames and differs from crossed molecular beams data. The
      accuracy of these isomer distributions is discussed in view of large
      uncertainties on the photoionization spectra of the pure C4H5 isomers. 

PMID- 26304771
TI  - Acceptance and Commitment Therapy and Selective Optimization with Compensation
      for Institutionalized Older People with Chronic Pain.
AB  - OBJECTIVE: Recent studies support the efficacy of Acceptance and Commitment
      Therapy (ACT) with people with chronic pain. In addition, Selective Optimization
      with Compensation strategies (SOC) can help the elderly with chronic pain to
      accept their chronic condition and increase functional autonomy. Our aim was to
      analyze the efficacy of an ACT treatment program combined with training in SOC
      strategies for elderly people with chronic pain living in nursing homes. METHODS:
      101 participants (mean age = 82.26; SD = 10.00; 78.6% female) were randomized to
      the intervention condition (ACT-SOC) or to a minimal support group (MS). Complete
      data are available for 53 participants (ACT-SOC: n = 27; MS: n = 26). Assessments
      of functional performance, pain intensity, pain acceptance, SOC strategies,
      emotional well being and catastrophizing beliefs were done preintervention and
      postintervention. RESULTS: Significant time by intervention changes (P = 0.05)
      were found in acceptance, pain related anxiety, compensation strategies, and pain
      interference in walking ability. Simple effects changes were found in acceptance
      (P = 0.01), selection strategies (P = 0.05), catastrophizing beliefs (P = 0.03),
      depressive symptoms (P = 0.05), pain anxiety (P = 0.01) and pain interference in
      mood and walking ability (P = 0.03) in the ACT-SOC group. No significant changes
      were found in the MS group. CONCLUSIONS: These results suggest that an ACT
      intervention combined with training in SOC strategies could help older people
      with pain to improve their emotional well being and their functional capability.

PMID- 26304772
TI  - Reactivity of a dihydroboron species: synthesis of a hydroborenium complex and an
      expedient entry into stable thioxo- and selenoxo-boranes.
AB  - The reaction of a recently synthesized dihydroboron species complexed with
      bis(phosphinimino)amide, LBH2 (), (L = [N(Ph2PN(2,4,6-Me3C6H2))2](-)) with 3
      equivalents of BH2Cl.SMe2 or one equivalent of BCl3 affords the first stable
      monohydridoborenium ion, [LBH](+)[HBCl3](-) () that is stable without a weakly
      coordinating bulky anion. Compound can also be prepared directly by refluxing LH
      with 3 equivalents of BH2Cl.SMe2. Interestingly, reaction of LBH2 () with
      elemental sulfur and selenium involves oxidative addition of S and Se into B-H
      bonds and subsequent release of H2S (or H2Se) from the intermediate LB(SH)2 (or
      LB(SeH)2) species forming stable compounds with terminal boron-chalcogen double
      bonds LB[double bond, length as m-dash]S () and LB[double bond, length as m
      dash]Se (). The electronic structures of compounds , and were elucidated by high
      resolution mass spectrometry, multi-nuclear NMR and single crystal X-ray
      diffraction studies. Ab initio calculations on are in excellent agreement with
      its experimental structure and clearly support the existence of the boron-sulfur
      double bond. 

PMID- 26304770
TI  - NEDD4 Regulates PAX7 Levels Promoting Activation of the Differentiation Program
      in Skeletal Muscle Precursors.
AB  - The transcription factor Pax7 regulates skeletal muscle stem cell (satellite
      cells) specification and maintenance through various mechanisms, including
      repressing the activity of the muscle regulatory factor MyoD. Hence, Pax7-to-MyoD
      protein ratios can determine maintenance of the committed-undifferentiated state
      or activation of the differentiation program. Pax7 expression decreases sharply
      in differentiating myoblasts but is maintained in cells (re)acquiring quiescence,
      yet the mechanisms regulating Pax7 levels based on differentiation status are not
      well understood. Here we show that Pax7 levels are directly regulated by the
      ubiquitin-ligase Nedd4. Our results indicate that Nedd4 is expressed in quiescent
      and activated satellite cells, that Nedd4 and Pax7 physically interact during
      early muscle differentiation-correlating with Pax7 ubiquitination and decline-and
      that Nedd4 loss of function prevented this effect. Furthermore, even transient
      nuclear accumulation of Nedd4 induced a drop in Pax7 levels and precocious muscle
      differentiation. Consequently, we propose that Nedd4 functions as a novel Pax7
      regulator, which activity is temporally and spatially controlled to modulate the
      Pax7 protein levels and therefore satellite cell fate.

PMID- 26304774
TI  - The influence of large-amplitude librational motion on the hydrogen bond energy
      for alcohol-water complexes.
AB  - The far-infrared absorption spectra have been recorded for hydrogen-bonded
      complexes of water with methanol and t-butanol embedded in cryogenic neon
      matrices at 2.8 K. The partial isotopic substitution of individual subunits
      enabled by a dual inlet deposition procedure provides for the first time
      unambiguous assignments of the intermolecular high-frequency out-of-plane and low
      frequency in-plane donor OH librational modes for mixed alcohol-water complexes.
      The vibrational assignments confirm directly that water acts as the hydrogen bond
      donor in the most stable mixed complexes and the tertiary alcohol is a superior
      hydrogen bond acceptor. The class of large-amplitude donor OH librational motion
      is shown to account for up to 5.1 kJ mol(-1) of the destabilizing change of
      vibrational zero-point energy upon intermolecular OHO hydrogen bond formation.
      The experimental findings are supported by complementary electronic structure
      calculations at the CCSD(T)-F12/aug-cc-pVTZ level of theory. 

PMID- 26304773
TI  - Hyperlipidemia-induced hepatic and small intestine ER stress and decreased
      paraoxonase 1 expression and activity is associated with HDL dysfunction in
      Syrian hamsters.
AB  - SCOPE: We aimed at investigating the mechanisms linking hyperlipidemia (HL) with
      dysfunctional HDL and its main antioxidant enzyme, paraoxonase1 (PON1). PON1
      expression and activity was determined in the small intestine, liver, and sera of
      normal and HL hamsters and associated with the ER stress (ERS) and the
      development of aortic valve lesions. METHODS AND RESULTS: Male Golden Syrian
      hamsters were fed standard chow (N) or standard diet with 3% cholesterol and 15%
      butter for 16 weeks. All hamsters on fat diet developed HL, 50% also
      hyperglycemia (HLHG) and a fourfold increased homeostasis model assessment of
      insuline resistance. PON1 expression was reduced in the small intestine and liver
      (N > HL > HLHG) along with the increased extent of ERS, oxidized lipids, and
      decreased expression of liver X receptors beta (LXRbeta) in the small intestine,
      peroxisome proliferator-activated receptor-gamma (PPARgamma) in the liver, and of
      the glucose transporter 4 in the myocardium. Serum PON1 levels decreased along
      with the increase of oxidized LDL and lesion areas of the aortic valves (N > HL >
      HLHG). CONCLUSION: The fat diet activates the ERS and oxidative stress, decreases
      LXRbeta, PPARgamma, and PON1 in the small intestine, liver, and sera of all HL
      animals, in parallel with the appearance of atherosclerotic lesions in the aortic
      valves.

PMID- 26304775
TI  - Working conditions and illicit psychoactive substance use among truck drivers in
      Brazil.
AB  - BACKGROUND: The aim of this study was to identify the role that working
      conditions play in predicting the consumption of illicit psychoactive substances
      (IPS) among truck drivers. METHODS: This cross-sectional study was conducted with
      truck drivers who transport grains to Paranagua Port, PR, Brazil. The truck
      drivers were interviewed, and they completed a self-administered questionnaire
      regarding their sociodemographics, lifestyles, working conditions, and
      consumption of IPS over the past 30 days. The statistical analysis included
      logistic regression models progressively adjusted for sociodemographic and
      lifestyle variables. RESULTS: A total of 670 male drivers with a mean age of 41.9
      (+/-11.1) years were assessed. The prevalence of IPS consumption over the past 30
      days was 10.9% (n=73). The drugs used primarily consisted of amphetamines (n=61).
      After adjusting for working characteristics, sociodemographic and lifestyle
      variables, the following working conditions were associated with the consumption
      of IPS: driving mostly at night (OR=3.91; 95% CI 1.75 to 8.74), driving while
      tired (OR=2.26; 95% CI 1.31 to 3.89), and earning a higher monthly income
      (OR=2.08; 95% CI 1.16 to 3.72). Drivers who were 39 years old or younger
      (OR=2.11; 95% CI 1.05 to 4.25) and not living with a partner (OR=2.22; 95% CI
      1.17 to 4.22) were also more likely to consume IPS. CONCLUSIONS: Driving mostly
      at night, being tired, and earning more increase the use of IPS among truck
      drivers, regardless of other working characteristics, sociodemographic, and
      lifestyle variables.

PMID- 26304776
TI  - Digestive cancers and occupational asbestos exposure: incidence study in a cohort
      of asbestos plant workers.
AB  - OBJECTIVE: The aim of our study was to estimate the incidence of digestive
      cancers within a cohort of asbestos-exposed workers. METHODS: Our study was based
      on a cohort of 2024 participants occupationally exposed to asbestos. The
      incidence of digestive cancers was calculated from 1 January 1978 to 31 December
      2009 and compared with levels among the local general population using
      Standardised Incidence Ratios (SIRs). Asbestos exposure was assessed using the
      company's job-exposure matrix. RESULTS: 119 cases of digestive cancer were
      observed within our cohort, for an expected number of 77 (SIR=1.54 (1.28 to
      1.85)). A significantly elevated incidence was observed for peritoneal
      mesothelioma, particularly in women. Significantly elevated incidences were also
      observed among men for: all digestive cancers, even when excluding peritoneal
      mesothelioma (SIR=1.50 (1.23 to 1.82)), oesophageal cancer (SIR=1.67 (1.08 to
      2.47)) and liver cancer (SIR=1.85 (1.09 to 2.92)). Concerning colorectal cancer,
      a significant excess of risk was observed for men with exposure duration above 25
      years (SIR=1.75 (1.05 to 2.73)). CONCLUSIONS: Our results are in favour of a link
      between long-duration asbestos exposure and colorectal cancer in men. They also
      suggest a relationship between asbestos exposure and cancer of the oesophagus in
      men. Finally, our results suggest a possible association with small intestine and
      liver cancers in men.

PMID- 26304777
TI  - Testicular germ cell tumours and parental occupational exposure to pesticides: a
      register-based case-control study in the Nordic countries (NORD-TEST study).
AB  - OBJECTIVES: A potential impact of exposure to endocrine disruptors, including
      pesticides, during intrauterine life, has been hypothesised in testicular germ
      cell tumour (TGCT) aetiology, but exposure assessment is challenging. This large
      scale registry-based case-control study aimed to investigate the association
      between parental occupational exposure to pesticides and TGCT risk in their sons.
      METHODS: Cases born in 1960 or onwards, aged between 14 and 49 years, and
      diagnosed between 1978 and 2013 in Denmark, Finland, Norway or Sweden, were
      identified from the respective nationwide cancer registries. Four controls per
      case were randomly selected from the general national populations, matched on
      year of birth. Information on parental occupation was collected through censuses
      or Pension Fund information and converted into a pesticide exposure index based
      on the Finnish National Job-Exposure Matrix. RESULTS: A total of 9569 cases and
      32,028 controls were included. No overall associations were found for either
      maternal or paternal exposures and TGCT risk in their sons, with ORs of 0.83 (95%
      CI 0.56 to 1.23) and of 1.03 (0.92 to 1.14), respectively. Country-specific
      estimates and stratification by birth cohorts revealed some heterogeneity.
      Cryptorchidism, hypospadias and family history of testicular cancer were risk
      factors but adjustment did not change the main results. CONCLUSIONS: This is the
      largest study on prenatal exposure to pesticides and TGCT risk, overall providing
      no evidence of an association. Limitations to assess individual exposure in
      registry-based studies might have contributed to the null result.

PMID- 26304778
TI  - Relative benefit of a stage of change approach for the prevention of
      musculoskeletal pain and discomfort: a cluster randomised trial.
AB  - OBJECTIVES: To examine the benefit of a psychological Stage of Change (SOC)
      approach, relative to standard ergonomics advice, for the prevention of work
      related musculoskeletal pain and discomfort (MSPD). METHODS: A cluster randomised
      trial was conducted in South Australia across a broad range of workplaces.
      Repeated face-to-face interviews were conducted onsite to assess MSPD, safety
      climate, job satisfaction and other factors. Changes in MSPD across intervention
      groups and time were investigated using Generalised Estimating Equation (GEE)
      methods. RESULTS: 25 workgroups (involving 242 workers) were randomly allocated
      to either a standard intervention or an intervention tailored according to SOC.
      The prevalence of MSPD increased for both groups, but was only significant for
      the standard group, in respect of lower back MSPD. Workers receiving tailored
      interventions were 60% less likely to experience lower back MSPD. After adjusting
      for age, gender and job satisfaction, it was found that company safety climate
      and length of employment were significantly correlated to the time-intervention
      effect. There was no correlation with workload. CONCLUSIONS: Compared with
      standard ergonomics advice to management, there was evidence of a benefit of
      stage-matched intervention for MSPD prevention, particularly for low back pain.
      Organisational safety climate should be taken into account when planning
      prevention programmes.

PMID- 26304780
TI  - Nutritional and health-promoting properties of bean paste fortified with onion
      skin in the light of phenolic-food matrix interactions.
AB  - The study examined the effect of fortification of bean paste with onion skin
      phenolics. The antioxidant potential and in vitro digestibility of nutrients in
      the light of phenolic-food matrix interactions were studied. Bean paste was
      supplemented with onion skin extracts in the range of 5-50 mg of phenolics per
      100 g of bean (C, O5-O50). Fortification increased the phenolic level and
      antioxidant activity of bean paste; however, the experimental values, in most
      cases, were significantly lower than those predicted. The digestive tract acted
      as an effective extractor of phenolics from the functional products but,
      surprisingly, the amounts of introduced phenolics had no significant effect on
      its determined levels. Additionally, after in vitro intestinal digestion a
      significant increase in the ability to quench free radicals was only observed in
      samples enriched with the highest amounts of phenolics (O50). After gastric and
      intestinal stages of digestion no significant effect of fortification on the
      albumin digestibility was observed. Contrarily, digestibility of globulins had
      decreased from 70% (C) up to 55% (O50) after gastric digestion and from 93% (C)
      up to 80% (O50) after intestinal digestion. These results were confirmed by SDS
      PAGE analysis, which indicates the presence of indigestible complexes after
      supplementation with phenolics. Moreover, a significant decrease in starch
      digestibility from 43% (C) to 21% (O50) was found. In conclusion, fortification
      improves the health-promoting properties of bean paste; however, the interactions
      of phenolics with the food matrix play an important role in the creation of the
      nutraceutical and nutritional quality of products. 

PMID- 26304779
TI  - Synthesis of strigolactones, a strategic account.
AB  - Strigolactones (SLs) constitute a new class of plant hormones that have received
      growing interest in recent years. They firstly became known as signalling
      molecules for host recognition by parasitic plants, and for symbiosis of plants
      with arbuscular mycorrhizal fungi. Furthermore, they are involved in numerous
      physiological processes in plants, such as the regulation of plant architecture
      and the response to abiotic factors. SLs are produced by plants in extremely low
      quantities, and they may be unstable during the purification process. Therefore,
      their total synthesis is highly relevant for confirming the structures assigned
      on the basis of spectroscopic and other physical data. A second important theme
      in SL research is the design and synthesis of SL analogues that have a simplified
      structure while still featuring the essential bioproperties. This review
      summarises the strategy and synthesis of naturally occurring SLs, and the design
      and synthesis of SL analogues with appreciable bioactivity.

PMID- 26304781
TI  - [18F-Fluorodeoxyglucose positron emission tomography and serum cytokines and
      matrix metalloproteinases in the assessment of disease activity in Takayasu's
      arteritis].
AB  - OBJECTIVE: To evaluate 18F-fluorodeoxyglucose (FDG) uptake on positron emission
      tomography-computed tomography (PET-CT)-and serum levels of different cytokines
      and matrix metalloproteinases (MMPs) in patients with Takayasu's arteritis (TA)
      and associations with disease activity. METHODS: Serum levels of tumor necrosis
      factor-alpha (TNF-alpha), interleukin (IL)-2, IL-6, IL-8, IL-12, IL-18, MMP-3 and
      MMP-9 were measured in 36 TA patients and 36 controls. Maximum standard uptake
      value (SUVmax) of 18F-FDG in arterial walls was determined by PET-CT scans. TA
      patients were classified as active disease, inactive disease and possible active
      disease. RESULTS: Serum IL-6 and MMP-3 levels were higher in TA patients than in
      controls (p<0.001). Serum IL-6 was higher in patients with active disease and in
      patients with possible active disease than in inactive disease (p<0.0001).
      Patients with active disease had higher serum TNFalpha levels than patients with
      inactive disease (p=0.049) while patients with possible active disease presented
      higher IL-18 levels than patients with inactive disease (p=0.046). Patients with
      active disease had higher SUVmax values than those with inactive disease
      (p=0.042). By ROC curve SUVmax was predictive of active disease in TA and values
      >=1.3 were associated with disease activity (p=0.039). Serum TNF-alpha levels
      were higher in patients with SUVmax >=1.3 than<1.3 (p=0.045) and controls
      (p=0.012). Serum IL-6 levels were higher in patients with SUVmax >=1.3 than in
      controls (p<0.001). No differences regarding other biomarkers were found between
      TA patients and controls. CONCLUSIONS: Higher serum IL-6 and TNFalpha levels as
      well as higher arterial 18F-FDG uptake are associated with active TA.

PMID- 26304782
TI  - Graphene/nano-porous silicon and graphene/bimetallic silicon nanostructures (Pt
      M, M: Pd, Ru, Rh), efficient electrocatalysts for the hydrogen evolution
      reaction.
AB  - In this work nano-porous silicon flour (Nano-PSiF) was synthesized first and then
      there was an investigation into its electrocatalytic activity for the
      electrochemical hydrogen evolution reaction (HER). The results showed that Nano
      PSiF has good electrocatalytic activity for the HER when compared with PSiF. In
      the second section, Pt and Pt-M (M = Pd, Rh, Ru) bimetallic silicon
      nanostructures were prepared by a direct reduction of the metal (Pt, Pt-Pd, Pt-Rh
      and Pt-Ru) on the surface of the PSiF by a galvanic exchange mechanism. The
      electrocatalytic activity of the bimetallic silicon nanostructures (Pt-M/PSiF)
      were evaluated for the HER. The results showed that all of the Pt-M/PSiFs have
      excellent electrocatalytic activity for the HER in a 0.5 mol L(-1) H2SO4
      solution. For the Pt/PSiF, the Tafel slope of Pt/PSiF was 46.9 mV dec(-1),
      indicating its excellent electrocatalytic activity for the HER and it is
      comparable with commercial Pt/C. On the other hand, the bimetallic silicon
      nanostructures showed better electrocatalytic activity than Pt/PSiF for the HER
      (lower Tafel slope, and higher alpha). Finally, exfoliated graphene oxide was
      electro-deposited on the surface of a glassy carbon electrode (eRGO/GCE) and used
      as a sub-layer for the Pt-M/PSiF. Then, the electrocatalytic activities of the
      bimetallic silicon nanostructures on the eRGO/GCE were investigated for the HER.
      The results showed that there was a higher electrocatalytic activity for Pt
      M/PSiF-eRGO/GCE when compared with Pt-M/PSiF-GCE. 

PMID- 26304783
TI  - Performance and nutrient digestibility in growing pigs fed wheat dried
      distillers' grain with solubles-containing diets supplemented with phytase and
      multi-carbohydrase.
AB  - Effect of supplementing wheat dried distillers' grain with solubles (DDGS)
      containing diet with enzymes on nutrient utilization by growing pigs was
      evaluated in two experiments. In Experiment 1, 60 pigs weighing ~30 kg were fed
      five diets that included a corn-based diet (Control), Control with 10% wheat DDGS
      (DDGS-PC), DDGS-PC without inorganic P source (DDGS-NC), and DDGS-NC plus phytase
      alone or with multi-carbohydrase for 4 weeks to determine average daily gain
      (ADG), average daily feed intake (ADFI) and gain-to-feed ratio (G:F). In
      Experiment 2, 30 barrows weighing 22 kg were fed five diets fed in Experiment 1
      to determine nutrient digestibility and retention. Pigs fed DDGS-PC and Control
      diets had similar ADG and G:F. The ADG and G:F for DDGS-PC diet were higher (P <
      0.05) than those for DDGS-NC diet. Phytase improved (P < 0.05) ADG, G:F, total
      tract P digestibility and P retention by 6.6, 8.7, 86.0 and 85.5%, respectively.
      Addition of multi-carbohydrase to phytase-supplemented diet did not affected
      growth performance, but reduced (P < 0.05) P retention. In conclusion, inclusion
      of 10% wheat DDGS in growing pig diet may not affect growth performance of
      growing pigs. Phytase supplementation to wheat DDGS-containing diet can eliminate
      the need for inorganic P supplement in pig diets. 

PMID- 26304784
TI  - New physiologically-relevant liver tissue model based on hierarchically
      cocultured primary rat hepatocytes with liver endothelial cells.
AB  - To develop an in vitro liver tissue equivalent, hepatocytes should be cocultured
      with liver non-parenchymal cells to mimic the in vivo physiological
      microenvironments. In this work, we describe a physiologically-relevant liver
      tissue model by hierarchically organizing layers of primary rat hepatocytes and
      human liver sinusoidal endothelial cells (TMNK-1) on an oxygen-permeable
      polydimethylsiloxane (PDMS) membrane, which facilitates direct oxygenation by
      diffusion through the membrane. This in vivo-mimicking hierarchical coculture was
      obtained by simply proceeding the overlay of TMNK-1 cells on the hepatocyte layer
      re-formed on the collagen immobilized PDMS membranes. The comparison of hepatic
      functionalities was achieved between coculture and sandwich culture with
      Matrigel, in the presence and absence of direct oxygenation. A complete double
      layered structure of functional liver cells with vertical contact between
      hepatocytes and TMNK-1 was successfully constructed in the coculture with direct
      oxygen supply and was well-maintained for 14 days. The hepatocytes in this
      hierarchical culture exhibited improved survival, functional bile canaliculi
      formation, cellular level polarization and maintenance of metabolic activities
      including Cyp1A1/2 activity and albumin production. By contrast, the two cell
      populations formed discontinuous monolayers on the same surfaces in the non
      oxygen-permeable cultures. These results demonstrate that (i) the direct
      oxygenation through the PDMS membranes enables very simple formation of a
      hierarchical structure consisting of a hepatocyte layer and a layer of TMNK-1 and
      (ii) we may include other non-parenchymal cells in this format easily, which can
      be widely applicable to other epithelial organs. 

PMID- 26304785
TI  - Comparison of situs ambiguous patterns between heterotaxy syndromes with
      polysplenia and asplenia.
AB  - OBJECTIVES: To compare the differences of visceral anomalies shown by computed
      tomography (CT) in patients with polysplenia syndrome (PS) or asplenia syndrome
      (AS). METHODS: This retrospective study was approved by the institutional review
      board, and informed consent was waived. Thirty-one patients with PS and 29
      patients with AS underwent chest-abdominal CT. The evaluated CT findings were as
      follows: the orientation of stomach, liver and gallbladder; short pancreas;
      azygous/hemiazygous continuation; ipsilateral position of the inferior vena cava
      and aorta; preduodenal portal vein; abnormal confluence of renal vein (defined as
      renal vein drains to the inferior vena cava or azygous/hemiazygous vein at the
      upper level of celiac trunk origin); gastrointestinal malrotation; and
      tracheobronchial tree. RESULTS: Azygous/hemiazygous continuation was seen in 74%
      (20 of 27)/0% (0 of 28) of PS/AS (P<0.0001), bilateral hyparterial bronchi in 75%
      (24 of 32)/5% (1 of 22), bilateral eparterial bronchi in 9% (3 of 32)/95% (21 of
      22), ipsilateral position of the inferior vena cava and aorta in 59% (16 of
      27)/89% (25 of 28), and abnormal confluence of renal vein in 7% (2 of 27)/57% (16
      of 28), respectively. No significant differences were found in the other
      anomalies. CONCLUSION: Significant differences in anomalous systemic venous
      connections and tracheobronchial anomaly were observed between PS and AS.
      Abnormal confluence of renal vein is relatively rare anomalous venous
      connections, but frequently observed in AS.

PMID- 26304786
TI  - Determination of melamine in aquaculture feed samples based on molecularly
      imprinted solid-phase extraction.
AB  - This research highlights the application of highly efficient molecularly
      imprinted solid-phase extraction for the preconcentration and analysis of
      melamine in aquaculture feed samples. Melamine-imprinted polymers were
      synthesized employing methacrylic acid and ethylene glycol dimethacrylate as
      functional monomer and cross-linker, respectively. The characteristics of
      obtained polymers were evaluated by scanning electron microscopy, Fourier
      transform infrared spectroscopy and binding experiments. The imprinted polymers
      showed an excellent adsorption ability for melamine and were applied as special
      solid-phase extraction sorbents for the selective cleanup of melamine. An off
      line molecularly imprinted solid-phase extraction procedure was developed for the
      separation and enrichment of melamine from aquaculture feed samples prior to high
      performance liquid chromatography analysis. Optimum molecularly imprinted solid
      phase extraction conditions led to recoveries of the target in spiked feed
      samples in the range 84.6-96.6% and the relative standard deviation less than
      3.38% (n = 3). The aquaculture feed sample was determined, and there was no
      melamine found. The results showed that the molecularly imprinted solid-phase
      extraction protocols permitted the sensitive, uncomplicated and inexpensive
      separation and pre-treatment of melamine in aquaculture feed samples. 

PMID- 26304787
TI  - Effects of supplementation with cellooligosaccharides on growth performance of
      weaned calves on pasture.
AB  - We conducted two feeding experiments to evaluate the effects of
      cellooligosaccharide (CE) supplementation on growth performance in grazing beef
      calves. Calf sex and age and duration of the experimental period differed between
      the experiments. Experiment 1 (10 weeks) used 5.6-month-old castrated males;
      Experiment 2 (13 weeks) used 3.9-month-old females. Eight Japanese Black calves
      were assigned to either a control group (CON) or an experimental group (CE) fed
      CE at a rate of 10 g/day mixed with concentrate. Calves were stocked in fields in
      which Kentucky bluegrass was dominant. In both experiments, average daily gain
      tended to be greater in CE than in CON, especially in late stages of experiments,
      but no significant differences in body weight changes were observed. In
      Experiment 2, final heart girth was larger in CE than in CON calves. We monitored
      rumen microbial community composition in Experiment 2 and found increases in
      fibrolytic bacteria and methanogenic archaea in CE calves, but the overall
      microbial composition did not differ between the groups. Our results suggest that
      supplementation with CE may positively affect growth performance in weaned calves
      on pasture, but longer-term CE supplementation may be required to exhibit the
      effect. 

PMID- 26304788
TI  - Optimization of an accelerated solvent extraction dispersive liquid-liquid
      microextraction method for the separation and determination of essential oil from
      Ligusticum chuanxiong Hort by gas chromatography with mass spectrometry.
AB  - In this study, an accelerated solvent extraction dispersive liquid-liquid
      microextraction coupled with gas chromatography and mass spectrometry was
      established and employed for the extraction, concentration and analysis of
      essential oil constituents from Ligusticum chuanxiong Hort. Response surface
      methodology was performed to optimize the key parameters in accelerated solvent
      extraction on the extraction efficiency, and key parameters in dispersive liquid
      liquid microextraction were discussed as well. Two representative constituents in
      Ligusticum chuanxiong Hort, (Z)-ligustilide and n-butylphthalide, were
      quantitatively analyzed. It was shown that the qualitative result of the
      accelerated solvent extraction dispersive liquid-liquid microextraction approach
      was in good agreement with that of hydro-distillation, whereas the proposed
      approach took far less extraction time (30 min), consumed less plant material
      (usually <1 g, 0.01 g for this study) and solvent (<20 mL) than the conventional
      system. To sum up, the proposed method could be recommended as a new approach in
      the extraction and analysis of essential oil. 

PMID- 26304789
TI  - The effect of the combination of dry needling and MET on latent trigger point
      upper trapezius in females.
AB  - AIM: The purpose of this clinical trial experiment was to compare the effects of
      the combination of dry needling (DN) and the muscle energy technique (MET) on the
      upper trapezius latent myofascial trigger point. METHOD: Sixty female patients,
      aged 18-30 with latent myofascial trigger points in the upper trapezius muscle
      were randomly divided into three groups: group 1 (n = 20) received DN and MET,
      group 2 (n = 20) received only MET, and group 3 (n = 20) received only DN. The
      visual analogue scale (VAS), pressure pain threshold (PPT), and range of active
      contra lateral flexion (CLF) were measured before each treatment. The patients
      were treated for three sessions in a one-week period with at least a two-day
      break between each session, and in session four, an assessment of primary
      outcomes was conducted without any treatment. RESULTS: All three treatment groups
      showed decreases in pain (p = 0.001) and increases in PPT levels (p = 0.001) as
      well as increases in CLF (p = 0.001). But the group receiving trigger point DN
      together with MET showed more significant improvement than the other two groups
      in VAS, PPT and ROM. No significant differences were found between the MET-only
      group and the DN-only group. CONCLUSION: Our results indicate that all three
      treatments used in this study were effective for treating MTP. According to this
      study, DN and MET is suggested as a new method for the treatment of MTP.

PMID- 26304790
TI  - Increased expression of lysosome membrane protein 2 in glomeruli of patients with
      idiopathic membranous nephropathy.
AB  - Urinary microvesicles constitute a rich source of membrane-bound and
      intracellular proteins that may provide important clues of pathophysiological
      mechanisms in renal disease. In the current study, we analyzed and compared the
      proteome of urinary microvesicles from patients with idiopathic membranous
      nephropathy (iMN), idiopathic focal segmental glomerulosclerosis (iFSGS), and
      normal controls using an approach that combined both proteomics and pathology
      analysis. Lysosome membrane protein-2 (LIMP-2) was increased greater than twofold
      in urinary microvesicles obtained from patients with iMN compared to
      microvesicles of patients with iFSGS and normal controls. Immunofluorescence
      analysis of renal biopsies confirmed our proteomics findings that LIMP-2 was
      upregulated in glomeruli from patients with iMN but not in glomeruli of diseased
      patients (iFSGS, minimal change nephropathy, IgA nephropathy,
      membranoproliferative glomerulonephritis) and normal controls. Confocal laser
      microscopy showed co-localization of LIMP-2 with IgG along the glomerular
      basement membrane. Serum antibodies against LIMP-2 could not be detected. In
      conclusion, our data show the value of urinary microvesicles in biomarker
      discovery and provide evidence for de novo expression of LIMP-2 in glomeruli of
      patients with iMN. 

PMID- 26304791
TI  - Rapid, targeted and culture-free viral infectivity assay in drop-based
      microfluidics.
AB  - A key viral property is infectivity, and its accurate measurement is crucial for
      the understanding of viral evolution, disease and treatment. Currently viral
      infectivity is measured using plaque assays, which involve prolonged culturing of
      host cells, and whose measurement is unable to differentiate between specific
      strains and is prone to low number fluctuation. We developed a rapid, targeted
      and culture-free infectivity assay using high-throughput drop-based
      microfluidics. Single infectious viruses are incubated in a large number of
      picoliter drops with host cells for one viral replication cycle followed by in
      drop gene-specific amplification to detect infection events. Using murine
      noroviruses (MNV) as a model system, we measure their infectivity and determine
      the efficacy of a neutralizing antibody for different variants of MNV. Our
      results are comparable to traditional plaque-based assays and plaque reduction
      neutralization tests. However, the fast, low-cost, highly accurate genomic-based
      assay promises to be a superior method for drug screening and isolation of
      resistant viral strains. Moreover our technique can be adapted to measuring the
      infectivity of other pathogens, such as bacteria and fungi. 

PMID- 26304792
TI  - The increasing threat of Pseudomonas aeruginosa high-risk clones.
AB  - The increasing prevalence of chronic and hospital-acquired infections produced by
      multidrug-resistant (MDR) or extensively drug-resistant (XDR) Pseudomonas
      aeruginosa strains is associated with significant morbidity and mortality. This
      growing threat results from the extraordinary capacity of this pathogen for
      developing resistance through chromosomal mutations and from the increasing
      prevalence of transferable resistance determinants, particularly those encoding
      carbapenemases or extended-spectrum beta-lactamases (ESBLs). P. aeruginosa has a
      nonclonal epidemic population structure, composed of a limited number of
      widespread clones which are selected from a background of a large quantity of
      rare and unrelated genotypes that are recombining at high frequency. Indeed,
      recent concerning reports have provided evidence of the existence of MDR/XDR
      global clones, denominated high-risk clones, disseminated in hospitals worldwide;
      ST235, ST111, and ST175 are likely those more widespread. Noteworthy, the vast
      majority of infections by MDR, and specially XDR, strains are produced by these
      and few other clones worldwide. Moreover, the association of high-risk clones,
      particularly ST235, with transferable resistance is overwhelming; nearly 100
      different horizontally-acquired resistance elements and up to 39 different
      acquired beta-lactamases have been reported so far among ST235 isolates.
      Likewise, MDR internationally-disseminated epidemic strains, such as the
      Liverpool Epidemic Strain (LES, ST146), have been noted as well among cystic
      fibrosis patients. Here we review the population structure, epidemiology,
      antimicrobial resistance mechanisms and virulence of the P. aeruginosa high-risk
      clones. The phenotypic and genetic factors potentially driving the success of
      high-risk clones, the aspects related to their detection in the clinical
      microbiology laboratory and the implications for infection control and public
      health are also discussed. 

PMID- 26304793
TI  - Letter in response to "High-frequency ultrasound in guiding needle insertion for
      microneurography" by Granata and colleagues.

PMID- 26304794
TI  - Ictal pattern on scalp EEG at onset of seizure in temporal lobe epilepsy: Old and
      new problems for epileptologists.

PMID- 26304795
TI  - Edge states and integer quantum Hall effect in topological insulator thin films.
AB  - The integer quantum Hall effect is a topological state of quantum matter in two
      dimensions, and has recently been observed in three-dimensional topological
      insulator thin films. Here we study the Landau levels and edge states of surface
      Dirac fermions in topological insulators under strong magnetic field. We examine
      the formation of the quantum plateaux of the Hall conductance and find two
      different patterns, in one pattern the filling number covers all integers while
      only odd integers in the other. We focus on the quantum plateau closest to zero
      energy and demonstrate the breakdown of the quantum spin Hall effect resulting
      from structure inversion asymmetry. The phase diagrams of the quantum Hall states
      are presented as functions of magnetic field, gate voltage and chemical
      potential. This work establishes an intuitive picture of the edge states to
      understand the integer quantum Hall effect for Dirac electrons in topological
      insulator thin films. 

PMID- 26304796
TI  - Effectiveness of the eccentric exercise therapy in physically active adults with
      symptomatic shoulder impingement or lateral epicondylar tendinopathy: A
      systematic review.
AB  - OBJECTIVES: To identify and criticize the evidence for the effectiveness of the
      eccentric exercise to treat upper limb tendinopathies. DESIGN: Systematic review.
      METHODS: Relevant randomized controlled trials (RCTs) were sourced using MEDLINE,
      SPORT Discus, Physiotherapy Evidence Database (PEDro) and CINAHL databases.
      Inclusion criteria were: (1) studies in English or Spanish; (2) adult
      participants with clinical diagnosis of tendinopathy; (3) RCT study design; (4)
      results regarding pain or strength were assessed; and (5) eccentric exercise was
      employed to treat upper extremity tendinopathies. Two blinded reviewers
      independently extracted data concerning trial methods, quality and outcomes.
      PEDro scale was employed to assess methodological quality. Results were
      summarized in a best evidence synthesis. RESULTS: The selected studies (n=12)
      scored an average of 6/10 based on the PEDro score. In 11 studies, pain decreased
      significantly with eccentric exercise, but only in five studies, the reduction
      was significantly better than in the non-eccentric group (in all or some of the
      parameters). Strength was assessed in nine studies; within-group evaluations show
      that strength significantly improved in the eccentric-group in seven studies,
      whereas inter-group changes were only significantly better in the eccentric-group
      in three studies for all the parameters and in two studies for some of the
      parameters. CONCLUSIONS: Eccentric exercise may reduce pain and improve strength
      in upper limb tendinopathies, but whether its effectiveness is much better than
      other forms of treatment remains questionable. Further investigations are needed,
      not only focused on shoulder impingement or epicondylar tendinopathy, but on
      tendinopathies in other areas of the upper limb.

PMID- 26304797
TI  - Intrinsic Nature of Stochastic Domain Wall Pinning Phenomena in Magnetic Nanowire
      Devices.
AB  - Finite temperature micromagnetic simulations are used to probe stochastic domain
      wall pinning behaviours in magnetic nanowire devices. By exploring field-induced
      propagation both below and above the Walker breakdown field it is shown that all
      experimentally observed phenomena can be comprehensively explained by the
      influence of thermal perturbations on the domain walls' magnetisation dynamics.
      Nanowires with finite edge roughness are also investigated, and these demonstrate
      how this additional form of disorder couples with thermal perturbations to
      significantly enhance stochasticity. Cumulatively, these results indicate that
      stochastic pinning is an intrinsic feature of DW behaviour at finite
      temperatures, and would not be suppressed even in hypothetical systems where
      initial DW states and experimental parameters were perfectly defined. 

PMID- 26304798
TI  - Impact of an Early Decrease in Systolic Blood Pressure on The Risk of Contrast
      Induced Nephropathy after Percutaneous Coronary Intervention.
AB  - BACKGROUND: The early postprocedural period was thought to be the rush hour of
      contrast media excretion, causing rapid and prolonged renal hypoperfusion, which
      was the critical time window for contrast-induced nephropathy (CIN). METHODS: 349
      consecutive patients were enrolled into the study. The relation between an early
      postprocedural decrease in systolic blood pressure (SBP) and the risk of CIN was
      assessed using multivariate logistic regression. RESULTS: A postprocedural
      decrease in SBP was observed in 63% of patients and CIN developed in 28 (8.0%)
      patients. The CIN group had a lower postprocedural SBP (114.5+/-13.5 vs. 123.7+/
      15.6mmHg, P=0.003) and a greater postprocedural decrease in SBP (16.2+/-19.1 vs.
      5.9+/-18.7mmHg, P=0.005) than the no-CIN group. ROC analysis revealed that the
      optimum cutoff value for the SBP decrease in detecting CIN was >10mmHg
      (sensitivity 60.7%, specificity 59.5%, AUC=0.66). Multivariate logistic
      regression analysis found that a postprocedural decrease in SBP >10mmHg was a
      significant independent predictor of CIN (OR 2.368, 95%CI: 1.043-5.379, P=0.039),
      after adjustment for other risk factors. CONCLUSION: An early moderate
      postprocedural decrease in SBP may increase the risk of CIN in patients
      undergoing PCI.

PMID- 26304799
TI  - Penetrating Cardiac Injury Managed Without Surgery but with Systemic
      Heparinisation.
AB  - A 36-year-old woman presented to hospital after a penetrating chest injury. She
      was haemodynamically stable. Echocardiography revealed left ventricular thrombus,
      with minimal pericardial effusion and no associated cardiac injuries. Intravenous
      anticoagulation was commenced for her intracardiac thrombus and her pericardial
      effusion was monitored with serial echocardiography. She remained well, was
      converted to warfarin and discharged home day 12 post admission, with cautious
      follow-up given her risk of late effusion and tamponade. Follow-up imaging
      revealed resolution of her intracardiac thrombus. She remains well to date. 

PMID- 26304800
TI  - Materials Prediction via Classification Learning.
AB  - In the paradigm of materials informatics for accelerated materials discovery, the
      choice of feature set (i.e. attributes that capture aspects of structure,
      chemistry and/or bonding) is critical. Ideally, the feature sets should provide a
      simple physical basis for extracting major structural and chemical trends and
      furthermore, enable rapid predictions of new material chemistries. Orbital radii
      calculated from model pseudopotential fits to spectroscopic data are potential
      candidates to satisfy these conditions. Although these radii (and their linear
      combinations) have been utilized in the past, their functional forms are largely
      justified with heuristic arguments. Here we show that machine learning methods
      naturally uncover the functional forms that mimic most frequently used features
      in the literature, thereby providing a mathematical basis for feature set
      construction without a priori assumptions. We apply these principles to study two
      broad materials classes: (i) wide band gap AB compounds and (ii) rare earth-main
      group RM intermetallics. The AB compounds serve as a prototypical example to
      demonstrate our approach, whereas the RM intermetallics show how these concepts
      can be used to rapidly design new ductile materials. Our predictive models
      indicate that ScCo, ScIr, and YCd should be ductile, whereas each was previously
      proposed to be brittle. 

PMID- 26304801
TI  - A Study of Phytolith-occluded Carbon Stock in Monopodial Bamboo in China.
AB  - Bamboo plants have been proven to be rich in phytolith-occluded carbon (PhytOC)
      and play an important role in reducing atmospheric concentrations of CO2. The
      object of this paper was to obtain more accurate methods for estimation of PhytOC
      stock in monopodial bamboo because previous studies may have underestimated it.
      Eight monopodial bamboo species, widely distributed across China, were selected
      and sampled for this study in their own typical distribution areas. There were
      differences (P < 0.05) both in phytolith content (Phytolith/dry biomass) across
      leaves, branches and culm, and in PhytOC content (PhytOC/dry biomass) across
      leaves and branches between species, with a trend of leaf > branch > culm. The
      average PhytOC stored in aboveground biomass and PhytOC production flux
      contributed by aboveground biomass varied substantially, and they were 3.28 and
      1.57 times corresponding dates in leaves, with the highest in Phyllostachys
      glauca McClure and lowest in Indocalamus tessellatus (Munro) Keng f. It can be
      concluded that it could be more accurate to estimate PhytOC stock or PhytOC
      production flux by basing on whole aboveground biomass rather than on leaf or
      leaf litter only. The whole biomass should be collected for more estimation of
      bamboo PhytOC sequestration capacity in the future. 

PMID- 26304802
TI  - Whole-Body MR Imaging Including Angiography: Predicting Recurrent Events in
      Diabetics.
AB  - OBJECTIVES: Whether whole-body MRI can predict occurrence of recurrent events in
      patients with diabetes mellitus. METHODS: Whole-body MRI was prospectively
      applied to 61 diabetics and assessed for arteriosclerosis and ischemic
      cerebral/myocardial changes. Occurrence of cardiocerebral events and diabetic
      comorbidites was determined. Patients were stratified whether no, a single or
      recurrent events arose. As a secondary endpoint, events were stratified into
      organ system-specific groups. RESULTS: During a median follow-up of 70 months, 26
      diabetics developed a total of 39 events; 18 (30%) developed one, 8 (13%)
      recurrent events. Between diabetics with no, a single and recurrent events, a
      stepwise higher burden was observed for presence of left ventricular (LV) hypo
      /akinesia (3/28/75%, p < 0.0001), myocardial delayed-contrast-enhancement
      (17/33/63%, p = 0.001), carotid artery stenosis (11/17/63%, p = 0.005),
      peripheral artery stenosis (26/56/88%, p = 0.0006) and vessel score
      (1.00/1.30/1.76, p < 0.0001). After adjusting for clinical characteristics, LV
      hypo-/akinesia (hazard rate ratio = 6.57, p < 0.0001) and vessel score (hazard
      rate ratio = 12.29, p < 0.0001) remained independently associated. Assessing
      organ system risk, cardiac and cerebral MR findings predicted more strongly
      events in their respective organ system. Vessel-score predicted both cardiac and
      cerebral, but not non-cardiocerebral, events. CONCLUSION: Whole-body MR findings
      predict occurrence of recurrent events in diabetics independent of clinical
      characteristics, and may concurrently provide organ system-specific risk. KEY
      POINTS: * Patients with long-standing diabetes mellitus are at high risk for
      recurrent events. * Whole-body MRI predicts occurrence of recurrent events
      independently of clinical characteristics. * The vessel score derived from whole
      body angiography is a good general risk-marker. * Whole-body MRI may also provide
      organ-specific risk assessment. * Current findings may indicate benefits of whole
      body MRI for risk stratification.

PMID- 26304803
TI  - Image quality and dose optimisation for infant CT using a paediatric phantom.
AB  - OBJECTIVE: To optimise image quality and reduce radiation exposure for infant
      body CT imaging. METHODS: An image quality CT phantom was created to model the
      infant body habitus. Image noise, spatial resolution, low contrast detectability
      and tube current modulation (TCM) were measured after adjusting CT protocol
      parameters. Reconstruction method (FBP, hybrid iterative and model-based
      iterative), image quality reference parameter, helical pitch and beam collimation
      were systematically investigated for their influence on image quality and
      radiation output. RESULTS: Both spatial and low contrast resolution were
      significantly improved with model-based iterative reconstruction (p < 0.05). A
      change in the helical pitch from 0.969 to 1.375 resulted in a 23% reduction in
      total TCM, while a change in collimation from 20 to 40 mm resulted in a 46% TCM
      reduction. Image noise and radiation output were both unaffected by changes in
      collimation, while an increase in pitch enabled a dose length product reduction
      of ~6% at equivalent noise. An optimised protocol with ~30% dose reduction was
      identified using model-based iterative reconstruction. CONCLUSIONS: CT technology
      continues to evolve and require protocol redesign. This work provides an example
      of how an infant-specific phantom is essential for leveraging this technology to
      maintain image quality while reducing radiation exposure. KEY POINTS: * A size
      specific phantom is critical in protocol development for infant CT. * New
      reconstruction technology enables ~30% dose reduction at equivalent image
      quality. * A consistent performance is observed for this scanner system across
      protocol changes. * A tradeoff exists between reducing exposure time and enabling
      tube current modulation.

PMID- 26304804
TI  - Self-purification processes of Lake Cerknica as a combination of wetland and SBR
      reactor.
AB  - Lake Cerknica is a periodically intermittent lake which may extend its surface up
      to 26 km(2) and reach 80 km(3) in volume. Lakes tend to age over time. Lake
      Cerknica does not possess properties of a real lake or those of usual wetlands
      thus making all of its physical, chemical, and biological processes unique. The
      feature with the greatest impact on plant development and animal life is the
      alternating nature of the lake where water from the lake is drained through the
      lake's bottom dries and refloods. Lake Cerknica was compared with a plant-based
      water treatment system and a sequential reactor with an approximately 6-month
      filling and emptying cycle. Lake Cerknica's basic processes of nutrient
      purification are the deposition of suspended nutrients on the lake bottom,
      integration of nutrients in plants, and partial denitrification.

PMID- 26304805
TI  - Comparison of the sensitivity of four native Canadian fish species to 17-alpha
      ethinylestradiol, using an in vitro liver explant assay.
AB  - Exposure to environmental estrogens and other endocrine-active chemicals can
      impact reproduction of freshwater fishes. While extensive data exists regarding
      the effect of estrogens on standard laboratory species, little is known about the
      sensitivity of freshwater fishes native to North America to these compounds.
      Current testing strategies for the toxicological assessment of contaminants still
      rely heavily on studies with live animals, which poses increasing concerns from
      an economical and ethical perspective. Therefore, the aim of the present study
      was to investigate the sensitivity of four native species, namely, northern pike
      (Esox lucius), walleye (Sander vitreus), white sucker (Catostomus commersoni),
      and juvenile white sturgeon (Acipenser transmontanus), to an environmental
      estrogen, 17alpha-ethinylestradiol (EE2), using an in vitro tissue explant
      approach. Transcript abundances of vitellogenin (VTG) as well as the estrogen
      receptors (ER) alpha and beta were used as the measuring endpoints as they
      represent well established biomarkers previously used to assess exposure to
      estrogens. Transcript abundance of VTG was upregulated in a concentration
      dependent manner in each species. Liver explants of male walleye were found to
      have the greatest sensitivity to EE2, with a lowest observable effect
      concentration of 300 ng/L (1.0 nM) for VTG transcript abundance, with juvenile
      white sturgeon having the greatest magnitude of VTG transcript upregulation in
      exposed tissue (15-fold relative to control). Exposure of liver explants to EE2
      resulted in no alteration in transcript abundance of ERbeta, whereas upregulation
      of ERalpha was observed in northern pike only. Based on in vitro expression of
      VTG, the species tested were among the species with greatest sensitivity to
      environmental estrogens tested to date.

PMID- 26304806
TI  - Water treatment by H2O2 and/or UV affects carbon nanotube (CNT) properties and
      fate in water and tannic acid solution.
AB  - The objective of the study was to estimate how water treatment (stimulation of
      real conditions) by H2O2 and/or UV affects carbon nanotube (CNT) properties and
      fate (stability/aggregation) in water and tannic acid solution. The processes
      studied had only a slight effect on SBET, porosity, and surface composition of
      CNTs. There was a change in the morphology of CNTs. After H2O2 and/or UV
      treatment, CNTs underwent shortening, opening up of their ends, and exfoliation.
      Treatment with H2O2 increased the content of oxygen in CNTs. A decrease was
      observed in the surface charge and in the mobility of CNTs, which caused an
      increase in their stability. UV irradiation of CNTs led to an increased incidence
      of defects that were manifested by both an increase of zeta potential and an
      increased mobility of CNT, whereas the presence of H2O2 during UV irradiation had
      only a slight effect on the parameters of the porous structure of nanotubes. 

PMID- 26304807
TI  - Effects of ambient PM2.5 on pathological injury, inflammation, oxidative stress,
      metabolic enzyme activity, and expression of c-fos and c-jun in lungs of rats.
AB  - Fine particulate matter (PM2.5) exposure is associated with morbidity and
      mortality induced by respiratory diseases and increases the lung cancer risk.
      However, the mechanisms therein involved are not yet fully clarified. In this
      study, the PM2.5 suspensions at different dosages (0.375, 1.5, 6.0, and 24.0
      mg/kg body weight) were respectively given to rats by the intratracheal
      instillation. The results showed that PM2.5 exposure induced inflammatory cell
      infiltration and hyperemia in the lung tissues and increased the inflammatory
      cell numbers in bronchoalveolar lavage fluid. Furthermore, PM2.5 significantly
      elevated the levels of pro-inflammatory mediators including tumor necrosis factor
      alpha (TNF-alpha), interleukin (IL)-6, IL-1beta, and intercellular adhesion
      molecule 1 (ICAM-1) and the expression of c-fos and c-jun in rat lungs exposed to
      higher dose of PM2.5. These changes were accompanied by decreases of activities
      of superoxide dismutase and increases of levels of malondialdehyde, inducible
      nitric oxide synthase, nitric oxide, cytochrome P450s, and glutathione S
      transferase. The results implicated that acute exposure to PM2.5 induced
      pathologically pulmonary changes, unchained inflammatory and oxidative stress
      processes, activated metabolic enzyme activity, and enhanced proto-oncogene
      expression, which might be one of the possible mechanisms by which PM2.5
      pollution induces lung injury and may be the important determinants for the
      susceptibility to respiratory diseases.

PMID- 26304808
TI  - Greenhouse gas emissions, soil quality, and crop productivity from a mono-rice
      cultivation system as influenced by fallow season straw management.
AB  - Straw management during fallow season may influence crop productivity, soil
      quality, and greenhouse gas (GHG) emissions from rice field. A 3-year field
      experiment was carried out in central China to examine the influence of different
      fallow season straw management practices on rice yield, soil properties, and
      emissions of methane (CH4) and nitrous oxide (N2O) from a mono-rice cultivation
      system. The treatments comprised an unfertilized control (CK), inorganic
      fertilization (NPK), rice straw burning in situ (NPK + RSB), rice straw mulching
      (NPK + RSM), and rice straw strip mulching with green manuring (NPK + RSM + GM).
      The maximum rice yield, soil organic carbon, soil total nitrogen, and available
      potassium were observed in NPK + RSM + GM treatment. Compared with NPK, the NPK +
      RSM + GM recorded 9% higher grain yield averaged across 3 years. However, NPK +
      RSM and NPK + RSB were statistically similar with NPK regarding grain yield. The
      NPK + RSM and NPK + RSM + GM recorded significantly higher CH4 emission during
      rice growing season as well as winter fallow; however, the response of N2O
      emissions was variable. The NPK + RSM and NPK + RSM + GM were statistically
      similar for annual cumulative CH4 and N2O emissions. The NPK + RSM + GM recorded
      103 and 72% higher straw-induced net economic benefits and soil organic carbon
      sequestration rate, and reduced net global warming potential by 27% as compared
      with NPK + RSM. Considering the benefits of soil fertility, higher crop
      productivity, and environmental safety, the NPK + RSM + GM could be the most
      feasible and sustainable option for mono-rice cultivation system in central
      China.

PMID- 26304809
TI  - Respective contributions of diet and medium to the bioaccumulation of
      pharmaceutical compounds in the first levels of an aquatic trophic web.
AB  - Nowadays, pharmaceuticals (PCs) are ubiquitous in aquatic ecosystems. It is known
      that these compounds have ecotoxic effects on aquatic organisms at low
      concentrations. Moreover, some of them can bioaccumulate inside organisms or
      trophic webs exposed at environmental concentrations and amplify ecotoxic
      impacts. PCs can bioaccumulate in two ways: exposure to a medium (e.g.,
      respiration, diffusion, etc.) and/or through the dietary route. Here, we try to
      assess the respective contributions of these two forms of contamination of the
      first two levels of an aquatic trophic web. We exposed Daphnia magna for 5 days
      to 0, 5, and 50 MUg/L (15)N-tamoxifen and then fed them with control and
      contaminated diets. We used an isotopic method to measure the tamoxifen content
      inside the daphnids after several minutes' exposure and every day before and
      after feeding. We found that tamoxifen is very bioaccumulative inside daphnids
      (BCF up to 12,000) and that the dietary route has a significant impact on
      contamination by tamoxifen (BAF up to 22,000), especially at low concentrations
      in medium.

PMID- 26304810
TI  - Effects of tamoxifen on autosomal genes regulating ovary maintenance in adult
      mice.
AB  - Environmental endocrine-disrupting chemicals (EDCs), known to bind to
      estrogen/androgen receptors and mimic native estrogens, have been implicated as a
      main source for increasing human reproductive and developmental deficiencies and
      diseases. Tamoxifen (TAM) is one of the most well-known antiestrogens with
      defined adverse effects on the female reproductive tract, but the mechanisms
      related to autosomal gene regulation governing ovary maintenance in mammals
      remain unclear. The expression pattern and levels of key genes and proteins
      involved in maintaining the ovarian phenotype in mice were analyzed. The results
      showed that TAM induced significant upregulation of Sox9, which is the testis
      determining factor gene. The results showed that TAM induced significant
      upregulation of Sox9, the testis-determining factor gene, and the expression
      level of Sox9 mRNA in the ovaries of mice exposed to 75 or 225 mg/kg bw TAM was 2
      and 10-fold that in the control group, respectively (p < 0.001). Furthermore,
      the testicular fibroblast growth factor gene, Fgf9, was also elevated in TAM
      treated ovaries. Accordingly, expression of the ovary development marker,
      forkhead transcription factor (FOXL2), and WNT4/FST signaling, were depressed.
      The levels of protein expression changed consistently with the target genes.
      Moreover, the detection of platelet/endothelial cell adhesion molecule 1 (PECAM
      1) in TAM-treated ovaries suggested the formation of vascular endothelial cells,
      which is a further evidence for the differentiation of the ovaries to a testis
      like phenotype. During this period, the level of 17beta-estradiol, progesterone,
      and luteinizing hormone decreased, while that of testosterone increased by 3.3
      fold (p = 0.013). The activation of a testis-specific molecular signaling cascade
      was a potentially important mechanism contributing to the gender disorder induced
      by TAM, which resulted in the differentiation of the ovaries to a testis-like
      phenotype in adult mice. Limited with a relatively higher exposure, the present
      study provided preliminary molecular insights into the sexual disorder induced by
      antiestrogens and compounds that interrupted estrogen signaling by other modes of
      action.

PMID- 26304811
TI  - Occurrence, source identification and ecological risk evaluation of metal
      elements in surface sediment: toward a comprehensive understanding of heavy metal
      pollution in Chaohu Lake, Eastern China.
AB  - In the present study, surface sediment samples from 48 sites covering the whole
      water area and three main estuaries of Chaohu Lake were collected to determine
      the concentrations of 25 metal elements using microwave-assisted digestion
      combined with ICP-MS. Spatial variation, source appointments, and contamination
      evaluation were examined using multivariate statistical techniques and pollution
      indices. The results show that for the elements Cd, Pb, Zr, Hf, U, Sr, Zn, Th,
      Rb, Sn, Cs, Tl, Bi, and Ba, which had higher coefficients of variation (CV), the
      concentrations were significantly higher in the eastern lake than in the western
      lake, but other elements with low CV values did not show spatial differences. The
      accumulation of Cu, Zn, Rb, Sr, Zr, Cd, Sn, Cs, Ba, Hf, Ta, Tl, Pb, Bi, U, and Th
      in the surface sediments was inferred as long-term agricultural cultivation
      impact, but that of Ti, V, Cr, Mn, Co, and Ni may have been a natural occurrence.
      The contribution from industrial and municipal impact was negligible, despite the
      rapid urbanization around the studied area. Principal component analysis-multiple
      linear regression (PCA-MLR) predicted the contribution from agricultural
      activities to range from 0.45 +/- 1.31% for Co to 92.7 +/- 17.7% for Cd. The
      results of the pollution indices indicate that Chaohu Lake was weakly to
      moderately affected by Ti, V, Cr, Mn, Co, and Ni but was severely contaminated by
      Hf and Cd. The overall pollution level in the eastern lake was higher than that
      in the western lake with respect to the pollution level index (PLI). Therefore,
      our results can help comprehensively understand the sediment contamination by
      metals in Chaohu Lake.

PMID- 26304812
TI  - Subcellular distribution and uptake mechanism of di-n-butyl phthalate in roots of
      pumpkin (Cucurbita moschata) seedlings.
AB  - Phthalate acid esters (PAEs) are of particular concern due to their potential
      environmental risk to human and nonhuman organisms. Although uptake of PAEs by
      plants has been reported by several researchers, information about the
      intracellular distribution and uptake mechanisms of PAEs is still lacking. In
      this study, a series of hydroponic experiments using intact pumpkin (Cucurbita
      moschata) seedlings was conducted to investigate how di-n-butyl phthalate (DnBP),
      one of the most frequently identified PAEs in the environment, enters and is
      distributed in roots. DnBP was transported into subcellular tissues rapidly in
      the initial uptake period (<12 h). More than 80% of DnBP was detected in the cell
      walls and organelles, which suggests that DnBP is primarily accumulated in these
      two fractions due to their high affinity to DnBP. The kinetics of DnBP uptake
      were fitted well with the Michaelis-Menten equation, suggesting that a carrier
      mediated process was involved. The application of 2,4-dinitrophenol and sodium
      vanadate reduced the uptake of DnBP by 37 and 26%, respectively, while aquaporin
      inhibitors, silver and glycerol, had no effect on DnBP uptake. These data
      demonstrated that the uptake of DnBP included a carrier-mediated and energy
      dependent process without the participation of aquaporins.

PMID- 26304813
TI  - Enhancements in nocturnal surface ozone at urban sites in the UK.
AB  - Analysis of diurnal patterns of surface ozone (O3) at multiple urban sites in the
      UK shows the occurrence of prominent nocturnal enhancements during the winter
      months (November-March). Whilst nocturnal surface ozone (NSO) enhancement events
      have been observed at other locations, this is the first time that such features
      have been demonstrated to occur in the UK and the second location globally. The
      observed NSO enhancement events in the UK were found to be so prevalent that they
      are clearly discernible in monthly diurnal cycles averaged over several years of
      data. Long-term (2000-2010) analysis of hourly surface ozone data from 18 urban
      background stations shows a bimodal diurnal variation during the winter months
      with a secondary nighttime peak around 0300 hours along with the primary daytime
      peak. For all but one site, the daily maxima NSO concentrations during the winter
      months exceeded 60 MUg/m(3) on >20 % of the nights. The highest NSO value
      recorded was 118 MUg/m(3). During the months of November, December, and January,
      the monthly averaged O3 concentrations observed at night (0300 h) even exceeded
      those observed in the daytime (1300 h). The analysis also shows that these NSO
      enhancements can last for several hours and were regional in scale, extending
      across several stations simultaneously. Interestingly, the urban sites in the
      north of the UK exhibited higher NSO than the sites in the south of the UK,
      despite their daily maxima being similar. In part, this seems to be related to
      the sites in the north typically having lower concentrations of nitrogen oxides.

PMID- 26304814
TI  - Mixotrophic cultivation of microalgae using industrial flue gases for biodiesel
      production.
AB  - In the present study, an attempt has been made to grow microalgae Scenedesmus
      quadricauda, Chlorella vulgaris and Botryococcus braunii in mixotropic
      cultivation mode using two different substrates, i.e. sewage and glucose as
      organic carbon sources along with flue gas inputs as inorganic carbon source. The
      experiments were carried out in 500 ml flasks with sewage and glucose-enriched
      media along with flue gas inputs. The composition of the flue gas was 7 % CO2,
      210 ppm of NO x and 120 ppm of SO x . The results showed that S. quadricauda
      grown in glucose-enriched medium yielded higher biomass, lipid and fatty acid
      methyl esters (FAME) (biodiesel) yields of 2.6, 0.63 and 0.3 g/L, respectively.
      Whereas with sewage, the biomass, lipid and FAME yields of S. quadricauda were
      1.9, 0.46, and 0.21 g/L, respectively. The other two species showed closer
      results as well. The glucose utilization was measured in terms of Chemical Oxygen
      Demand (COD) reduction, which was up to 93.75 % by S. quadricauda in the glucose
      flue gas medium. In the sewage-flue gas medium, the COD removal was achieved up
      to 92 % by S. quadricauda. The other nutrients and pollutants from the sewage
      were removed up to 75 % on an average by the same. Concerning the flue gas
      treatment studies, S. quadricauda could remove CO2 up to 85 % from the flue gas
      when grown in glucose medium and 81 % when grown in sewage. The SO x and NO x
      concentrations were reduced up to 50 and 62 %, respectively, by S. quadricauda in
      glucose-flue gas medium. Whereas, in the sewage-flue gas medium, the SO x and NO
      x concentrations were reduced up to 45 and 50 %, respectively, by the same. The
      other two species were equally efficient however with little less significant
      yields and removal percentages. This study laid emphasis on comparing the
      feasibility in utilization of readily available carbon sources like glucose and
      inexpensive leftover carbon sources like sewage by microalgae to generate energy
      coupled with economical remediation of waste. Therefore on an industrial scale,
      the sewage is more preferable. Because the results obtained in the laboratory
      demonstrated both sewage and glucose-enriched nutrient medium are equally
      efficient for algae cultivation with just a slight difference. Essentially, the
      sewage is cost effective and easily available in large quantities compared to
      glucose. 

PMID- 26304815
TI  - BMAA extraction of cyanobacteria samples: which method to choose?
AB  - beta-N-Methylamino-L-alanine (BMAA), a neurotoxin reportedly produced by
      cyanobacteria, diatoms and dinoflagellates, is proposed to be linked to the
      development of neurological diseases. BMAA has been found in aquatic and
      terrestrial ecosystems worldwide, both in its phytoplankton producers and in
      several invertebrate and vertebrate organisms that bioaccumulate it. LC-MS/MS is
      the most frequently used analytical technique in BMAA research due to its high
      selectivity, though consensus is lacking as to the best extraction method to
      apply. This study accordingly surveys the efficiency of three extraction methods
      regularly used in BMAA research to extract BMAA from cyanobacteria samples. The
      results obtained provide insights into possible reasons for the BMAA
      concentration discrepancies in previous publications. In addition and according
      to the method validation guidelines for analysing cyanotoxins, the TCA protein
      precipitation method, followed by AQC derivatization and LC-MS/MS analysis, is
      now validated for extracting protein-bound (after protein hydrolysis) and free
      BMAA from cyanobacteria matrix. BMAA biological variability was also tested
      through the extraction of diatom and cyanobacteria species, revealing a high
      variance in BMAA levels (0.0080-2.5797 MUg g(-1) DW). 

PMID- 26304816
TI  - Cryptosporidium: a first step toward tractability.
AB  - The child-killer and famously recalcitrant parasite Cryptosporidium is the latest
      organism to yield to the magic of CRISPR/Cas9. The ability to knockout genes and
      introduce markers promises a new heyday for drug discovery and vaccine
      development as well as the basic biology of these fascinating parasites. 

PMID- 26304817
TI  - Control of Dzyaloshinskii-Moriya interaction in Mn(1-x)Fe(x)Ge: a first
      principles study.
AB  - Motivated by the recent experiment on the size and helicity control of skyrmions
      in Mn(1-x)Fe(x)Ge, we study how the Dzyaloshinskii-Moriya (DM) interaction
      changes its size and sign in metallic helimagnets. By means of first-principles
      calculations, we successfully reproduce the non-trivial sign change of the DM
      interaction observed in the experiment. While the DM interaction sensitively
      depends on the carrier density or the detail of the electronic structure such as
      the size of the exchange splitting, its behavior can be systematically understood
      in terms of the distribution of anticrossing points in the band structure. By
      following this guiding principle, we can even induce gigantic anisotropy in the
      DM interaction by applying a strain to the system. These results pave the new way
      for skyrmion crystal engineering in metallic helimagnets.

PMID- 26304818
TI  - Studying Ancient Anthropogenic Impacts on Current Floral Biodiversity in the
      Southern Levant as reflected by the Philistine Migration.
AB  - Human migrations across geographic boundaries can facilitate the introduction of
      new husbandry practices and dispersal of plants and animals, resulting in changes
      in biodiversity. As previously demonstrated, the 12th century BCE Philistine
      migration-to the southern Levantine littoral, involved the transportation of pigs
      from Europe, engendering long term genetic displacement of local Near Eastern
      haplotypes. Building on this, and combining biogeographical methods of Floral
      List comparisons with archaeological data, we have elucidated the Philistine
      impact on Southern Levantine floral ecosystems. We demonstrate that previously
      unexploited local plants were incorporated into the Philistine milieu, and new
      species were introduced-from Europe, the Aegean, Egypt and Mesopotamia -resulting
      in the earliest locally cultivated sycamore, cumin, coriander, bay tree and opium
      poppy. This research has highlighted the impact of past cultures on the formation
      of floral ecosystems and their long-term effects on contemporary local biological
      diversity. 

PMID- 26304819
TI  - Glyceraldehyde caused Alzheimer's disease-like alterations in diagnostic marker
      levels in SH-SY5Y human neuroblastoma cells.
AB  - Clinical evidence has implicated diabetes mellitus as one of the risk factors for
      the development and progression of Alzheimer's disease (AD). However, the
      neurotoxic pathway activated due to abnormalities in glucose metabolism has not
      yet been identified in AD. In order to investigate the relationship between
      impaired cerebral glucose metabolism and the pathophysiology of AD, SH-SY5Y human
      neuroblastoma cells were exposed to glyceraldehyde (GA), an inhibitor of
      glycolysis. GA induced the production of GA-derived advanced glycation end
      products (GA-AGEs) and cell apoptosis, glycolytic inhibition, decreases in the
      medium concentrations of diagnostic markers of AD, such as amyloid beta 1-42
      (Abeta42), and increases in tau phosphorylation. These results suggest that the
      production of GA-AGEs and/or inhibition of glycolysis induce AD-like alterations,
      and this model may be useful for examining the pathophysiology of AD. 

PMID- 26304820
TI  - One of the Mechanisms to Increase HSV-1 Uptake in HSV-1-Infected, Activated T
      Lymphocytes Is the Formation of Filopodia.
AB  - OBJECTIVES: To explore the host transcription factor E2F-1 and/or any mechanisms
      that may support viral entry and its effect on the HSV-1 production in anti-CD3
      activated Jurkat cells. METHODS: The expressions of ICP4, HVEM and E2F-1 were
      studied using reverse transcription-PCR and Western blot. HSV-1 production was
      determined by plaque titration assay and HSV-1 DNA load was quantified by real
      time PCR. The viral uptake was observed by electron microscopy. RESULTS: In anti
      CD3-activated Jurkat cells, there was a significant increase in the HSV-1
      production. The expression of ICP4 mRNA after HSV-1 infection occurred 2 h prior
      to the synthesis of the ICP4 protein, which was significantly higher in activated
      than nonactivated T cells. There were no significant differences in the
      expressions of E2F-1 mRNA. The HVEM expression was positively correlated with the
      HSV-1 DNA in the activated T cells. From the electron micrograph, the formations
      of filopodia were observed only in HSV-1-infected, activated cells. CONCLUSIONS:
      High expressions of viral receptor protein and filopodia formations are the key
      factors that enhance the HSV-1 entry into activated T lymphocytes, resulting in
      an increased production of the virus.

PMID- 26304821
TI  - Metronidazole Toxicity in Cockayne Syndrome: A Case Series.
AB  - Cockayne syndrome (CS) is a rare genetic disorder characterized by small stature,
      intellectual disability, and accelerated pathologic aging. Through the Cockayne
      Syndrome Natural History Study, we have identified 8 cases of acute hepatic
      failure after metronidazole administration (8% of our cohort), 3 of which were
      fatal. The interval between initial administration and death was 6 to 11 days.
      Two of these patients also experienced acute neurologic deficit. Both
      hepatotoxicity and acute neurologic deficit have been reported previously as
      extremely rare adverse events after metronidazole administration. However, we
      have not identified any patients with CS who have received metronidazole without
      serious adverse effects. We recommend that a diagnosis of CS be considered an
      absolute contraindication to the use of metronidazole. 

PMID- 26304823
TI  - Incidence, Trends, and Survival of Children With Embryonal Tumors.
AB  - BACKGROUND: Central nervous system (CNS) and non-CNS embryonal tumors occur
      principally in children and are rarely seen in adults. The incidence rates for
      rare entities such as atypical teratoid/rhabdoid tumors (AT/RT) or primitive
      neuroectodermal tumors in the CNS are rarely published. Incidence rates for
      certain subgroups, such as hepatoblastomas, have been increasing in some
      countries. METHODS: Data of 8337 embryonal tumors, registered in children (0-14
      years) between 1991 and 2012 (for AT/RT 2000-2012) in the population-based German
      Childhood Cancer Registry with complete national coverage were analyzed for
      incidence rates, time trends, and survival. RESULTS: For most entities, the
      incidence rates were the highest for children <1 year. An important exception was
      medulloblastomas, which occurred mainly in 1- to 9-year-olds. Neuroblastomas and
      ganglioneuroblastomas as well as Wilms tumors (nephroblastomas) had the highest
      age standardized incidence rates (13.7 and 9.4 per million, respectively). A
      statistically significant increasing trend for hepatoblastomas (annual average
      percent change 4.6%) was detected. The survival probabilities varied between the
      diagnostic groups: primitive neuroectodermal tumors and AT/RT had the lowest and
      retinoblastomas the highest. The survival was dependent on the age at diagnosis,
      the most extreme examples being neuroblastomas, for which the survival
      probability declined steeply for children >=1 year and medulloblastomas, for
      which the highest survival was seen for 10- to 14-year-olds. CONCLUSIONS: This
      study presents a comprehensive overview of pediatric embryonal tumors from a well
      established, complete nationwide cancer registry. Significant increasing trend
      for hepatoblastomas was detected for the first time in Europe.

PMID- 26304822
TI  - Parent/Adolescent Weight Status Concordance and Parent Feeding Practices.
AB  - BACKGROUND: Previous studies have examined the independent influence of mother's
      weight status or child's weight status on parents' use of specific feeding
      practices (ie, food restriction, pressure-to-eat). However, studies have not
      examined the mutual influence of parents' and adolescents' weight status on
      parents' feeding practices. This study examines the relationship between parent
      and adolescent weight status concordance and discordance and parent feeding
      practices. METHODS: Data from 2 linked population-based studies, Eating and
      Activity in Teens (EAT) 2010 and Families and Eating and Activity in Teens (F
      EAT), were used for cross-sectional analysis. Parents (n = 3252; 63% female; mean
      age 42.6 years) and adolescents (n = 2153; 54% female; mean age 14.4 years) were
      socioeconomically and racially/ethnically diverse. Anthropometric assessments and
      surveys were completed at school by adolescents, and surveys were completed at
      home by parents. RESULTS: Parents used the highest levels of pressure-to-eat
      feeding practices when parents and adolescents were both nonoverweight compared
      with all other combinations of concordant and discordant parent/adolescent weight
      status categories. Additionally, parents used the highest levels of food
      restriction when parents and adolescents were both overweight/obese compared with
      all other combinations of concordant and discordant parent/adolescent weight
      status categories. Sensitivity analyses with 2-parent households revealed similar
      patterns. CONCLUSIONS: Results suggest that parents use feeding practices in
      response to both their adolescents' and their own weight status. Results may
      inform health care providers and public health interventionists about which
      parent/adolescent dyads are at highest risk for experiencing food restriction or
      pressure-to-eat parent feeding practices in the home environment and whom to
      target in interventions.

PMID- 26304824
TI  - Concurrent Respiratory Viruses and Kawasaki Disease.
AB  - BACKGROUND: The diagnosis of Kawasaki disease (KD) remains challenging without a
      definitive diagnostic test and currently is guided by using clinical patient
      characteristics and supported by laboratory data. The role of respiratory viruses
      in the pathogenesis of KD is not fully understood. METHODS: Charts of patients
      with KD admitted to Children's Hospital Colorado from January 2009 to May 2013
      were retrospectively reviewed. Patients with KD who had a nasopharyngeal wash
      submitted for multiplex polymerase chain reaction (PCR) viral testing were
      included. Clinical characteristics, laboratory data, and outcomes of patients
      with and without positive respiratory viral PCR results were compared. RESULTS:
      Of 222 patients with KD admitted to the hospital, 192 (86%) had a respiratory
      viral PCR test performed on or shortly after admission. Ninety-three (41.9%) of
      the 192 patients with KD had a positive respiratory viral PCR, and the majority
      were positive for rhinovirus/enterovirus. No statistically significant
      differences were found in the clinical characteristics and laboratory values
      between the groups with and without positive respiratory viral PCR findings. Both
      groups had the same frequency of upper respiratory and gastrointestinal symptoms
      and had the same incidence of admission to the PICU, intravenous immunoglobulin
      resistant disease, and coronary artery lesions. CONCLUSIONS: No differences in
      clinical presentations or outcomes in children with KD stratified according to
      positive or negative respiratory viral PCR testing were observed. A positive
      respiratory viral PCR or presence of respiratory symptoms at the time of
      presentation should not be used to exclude a diagnosis of KD.

PMID- 26304825
TI  - Improving Pneumococcal Vaccination in Pediatric Rheumatology Patients.
AB  - BACKGROUND AND OBJECTIVE: Many pediatric rheumatology patients are at increased
      risk of pneumococcal disease secondary to a deficient immune system and/or
      immunosuppressive medications. The goal of this study was to improve pneumococcal
      vaccination rates in this high-risk population. METHODS: Eligible patients
      included children at least 2 years old and adults with systemic lupus
      erythematosus and/or currently on immunosuppressive medication. Interventions
      included a presentation to rheumatology providers,creation of immunization
      algorithm, previsit planning, placing reminders on clinic forms, and sending
      reminder e-mails to providers. Chart reviews were performed, and control charts
      were established to portray change in immunization rates. RESULTS: The
      preintervention immunization rates for 90 patient visits compared with the
      immunization rates for the 53-week postintervention period with 1033 patient
      visits and 299 separate patients were all statistically significant.The 13-valent
      pneumococcal conjugate vaccine rate increased from 6.7% to48.4% (x2 = 58.3, P ,
      .001), 23-valent pneumococcal polysaccharide vaccinerate increased from 8.9% to
      28.4% (x2 = 16.0, P , .001), and combined rate increased from 0% to 23.2% (x2 =
      25.2, P , .001). The improvement was sustained with shifts in the data for each
      vaccine and combined immunizations for final average rates of 60.9% for 13-valent
      pneumococcal conjugate vaccine, 39.2% for 23-valent pneumococcal polysaccharide
      vaccine,and 33.7% for combined. CONCLUSIONS: Pneumococcal vaccination is an
      important part of the care for systemic lupus erythematosus patients and patients
      on immunosuppressive medications. Simple interventions through this quality
      improvement project led to a marked increase in pneumococcal vaccination rates in
      this vulnerable population.

PMID- 26304826
TI  - Management of Congenital Tracheal  Stenosis.
AB  - Congenital tracheal stenosis (CTS) is a serious and rare condition. In most
      cases, stenotic lesions are composed of complete tracheal rings of cartilage.The
      severity of symptoms correlates with the length of affected trachea, the presence
      of concomitant respiratory conditions, degree of luminal narrowing,and any
      bronchial involvement. Critically, CTS is a disorder that can lead to life
      threatening respiratory insufficiency in children. Thus, it is a clinical entity
      that demands timely diagnosis and treatment. This review will firstly discuss the
      anatomy and pathophysiology of CTS and outline the various clinical presentations
      associated with the disorder. In addition, methods of diagnosis and treatment
      strategies will be reviewed, with a focus on contemporary surgical techniques.
      Finally, postoperative care of patients with CTS will be reviewed, and a
      contemporary multidisciplinary management approach will be presented.

PMID- 26304827
TI  - Outcome of Patients Initiating Chronic  Peritoneal Dialysis During the First 
      Year of Life.
AB  - BACKGROUND AND OBJECTIVE: Among children with end-stage renal disease (ESRD),
      those who abstract initiated chronic dialysis during the first year of life
      historically were less likely to survive or receive a kidney transplant compared
      with those who initiated dialysis later in childhood.We hypothesized that
      recently treated infants have experienced improved outcomes. METHODS: We queried
      the North American Pediatric Renal Trials and Collaborative Studies database,
      obtaining information on 628 children who initiated maintenance peritoneal
      dialysis for treatment of ESRD at ,1 year of age. We further subcategorized these
      children by age(neonates, #31 days and infants, 32-365 days) and date of dialysis
      initiation (past,1992-1999, and recent, 2000-2012). RESULTS: Survival while on
      dialysis and overall survival were significantly better among neonates and
      infants in the recent cohort. Overall survival at 3 years after dialysis
      initiation was 78.6%and 84.6% among the recently treated neonates and infants,
      respectively. Neonates and infants in the recent cohort also were more likely to
      terminate dialysis for transplantation, and graft survival was improved among
      recently transplanted infants (3-year graft survival 92.1%). CONCLUSIONS: Among
      children who initiate chronic peritoneal dialysis for treatment of ESRD in the
      first year of life, survival has improved in recent years. Graft survival also
      has improved for the subset of these patients who received a kidney transplant.

PMID- 26304828
TI  - Computed Tomography and Shifts to  Alternate Imaging Modalities in  Hospitalized
      Children.
AB  - BACKGROUND: Many studies have demonstrated a rise in computed tomography (CT)
      utilization in abstract children's hospitals. However, CT utilization may be
      declining, perhaps due to awareness of potential hazards of pediatric ionizing
      radiation, such as increased risk of malignancy. Th e objective is to assess the
      trend in CT utilization in hospitalized children at freestanding children's
      hospitals from 2004 to 2012 and we hypothesize decreases are associated with
      shifts to alternate imaging modalities. METHODS: Multicenter cross-sectional
      study of children admitted to 33 pediatric tertiary-care hospitals participating
      in the Pediatric Health Information System between January 1, 2004, and December
      31, 2012. The rates of CT, ultrasound, and MRI for the top 10 All-Patient Refined
      Diagnosis Related Groups (APR-DRGs) for which CT was performed in 2004 were
      determined by billing data. Rates of each imaging modality for those top 10 APR
      DRGs were followed through the study period. Odds ratios of imaging were adjusted
      for demographics and illness severity. RESULTS: For all included APR-DRGs except
      ventricular shunt procedures and nonbacterial gastroenteritis, the number of
      children imaged with any modality increased. CT utilization decreased for all APR
      DRGs (P values , .001). For each of the APR-DRGs except seizure and infections of
      upper respiratory tract, the decrease in CT was associated with a significant
      rise in an alternative imaging modality (P values # .005). CONCLUSIONS: For the
      10 most common APR-DRGs for which children received CT in 2004,a decrease in CT
      utilization was found in 2012. Alternative imaging modalities for 8 of the
      diagnoses were used.

PMID- 26304829
TI  - Inhibition of Angiofibromas in  a Tuberous Sclerosis Patient Using  Topical
      Timolol 0.5% Gel.
AB  - Angiofibromas are the most recognized cutaneous manifestations of tuberous
      sclerosis complex. Angiofibromas can be associated with disfigurement, bleeding,
      pruritus, and erythema and may lead to significant psychosocial consequences for
      affected patients. Histopathologically, angiofibromas consist of a mixture of
      vascular and interstitial cells. Traditional treatment options include
      cryotherapy, electrocoagulation, radiofrequency ablation, dermabrasion, laser
      treatment, and topical agents such as podophyllotoxin. However, complications
      such as pain, postinflammatory hyperpigmentation, scarring, and the frequent
      recurrence rate reduce the utility of these treatment options. The introduction
      of topical rapamycin marked a turning point for treatment of facial
      angiofibromas; however, the lack of a standardized formulation, limited insurance
      coverage, and significant financial cost restrict universal access for patients
      and their caregivers. Both oral and topical beta-blockers have proven extremely
      effective treatments for superficial vascular tumors such as hemangiomas and
      pyogenic granulomas. Topical beta-blockers may potentially be useful for
      treatment of angiofibromas considering these lesions also contain a vascular
      component. Here we present an exploratory case report of a patient with tuberous
      sclerosis complex who had significant clinical improvement of her facial
      angiofibromas utilizing a "split-face" comparison protocol of topical timolol
      0.5% gel after full-field treatment with ablative fractional laser resurfacing
      and pulsed-dye laser.

PMID- 26304830
TI  - Preterm Birth and Poor Fetal Growth  as Risk Factors of Attention-Deficit/ 
      Hyperactivity Disorder.
AB  - BACKGROUND: Previous studies have shown an association between prematurity and
      attention- abstract deficit/hyperactivity disorder (ADHD). Results concerning
      late preterm infants are controversial, and studies examining fetal growth
      represented by weight for gestational age are scarce. Our objective was to
      examine the association between gestational age by each week of fetal maturity,
      weight for gestational age, and ADHD. METHODS: In this population-based study, 10
      321 patients with ADHD, diagnosed according to the International Classification
      of Diseases and 38 355 controls individually matched for gender, date and place
      of birth, were identified from Finnish nationwide registers. Perinatal data were
      obtained from the Finnish Medical Birth Register. Conditional logistic regression
      was used to examine the association between gestational age, weight for
      gestational age, and ADHD after controlling for confounding factors. RESULTS: The
      risk of ADHD increased by each declining week of gestation. The associations were
      robust after adjusting for confounders. An elevated risk also was seen among late
      preterm and early term infants. As for fetal growth, the odds ratio showed a U
      shaped curve with an increased risk seen when the weight for gestational age was
      1 SD below and 2 SD above the mean. CONCLUSIONS: Our findings suggest that each
      gestational week has significance for child's subsequent neurodevelopment and
      risk for ADHD. We also showed that poor fetal growth increased the risk of ADHD.
      This highlights the importance of taking into account both prematurity and poor
      fetal growth when planning the timing of birth as well as later follow-up and
      support policies.

PMID- 26304832
TI  - Discordant Clinical Course of Vitamin-D-Hydroxylase (CYP24A1) Associated
      Hypercalcemia in Two Adult Brothers With Nephrocalcinosis.
AB  - BACKGROUND/AIMS: Hypercalcemia can result in nephrocalcinosis/nephrolithiasis and
      may lead to renal failure. Idiopathic infantile hypercalcemia is caused by
      mutations of the CYP24A1 gene, which regulates vitamin D activity. Classically
      infants present with hypercalcemia. Recently, a number of individuals have been
      reported with late onset clinical manifestation or late diagnosis in adulthood.
      All these patients are believed to show hypercalciuria. METHODS: We report a 24
      year old patient of healthy consanguine parents. Genetic analysis was performed
      by Sanger sequencing of the CYP24A1 gene in the index patient and targeted exon 2
      analysis of all other family members. RESULTS: The patient was hospitalized with
      severe malaise during an acute EBV-infection. He showed hypercalcemia > 3mmol/l
      and acute, hypovolemic renal failure with profound nephrocalcinosis, but no
      hypercalciuria. Genetic workup revealed a homozygous loss-of-function mutation
      p.E143del in the CYP24A1 gene. His clinically asymptomatic brother showed
      nephrocalcinosis of lesser degree. Repeatedly, low parathyroid hormone levels
      were detected in both brothers. CONCLUSION: This family displays the highly
      variable phenotype of CYP24A1 biallelic mutation carriers. CYP24A1 associated
      disease is an important differential diagnosis for the workup and counseling of
      infants as well as adults with hypercalcemia since a proper genetic diagnosis may
      result in therapeutic consequences.

PMID- 26304831
TI  - Glycosyltransferase ST6GAL1 contributes to the regulation of pluripotency in
      human pluripotent stem cells.
AB  - Many studies have suggested the significance of glycosyltransferase-mediated
      macromolecule glycosylation in the regulation of pluripotent states in human
      pluripotent stem cells (hPSCs). Here, we observed that the sialyltransferase
      ST6GAL1 was preferentially expressed in undifferentiated hPSCs compared to non
      pluripotent cells. A lectin which preferentially recognizes alpha-2,6 sialylated
      galactosides showed strong binding reactivity with undifferentiated hPSCs and
      their glycoproteins, and did so to a much lesser extent with differentiated
      cells. In addition, downregulation of ST6GAL1 in undifferentiated hPSCs led to a
      decrease in POU5F1 (also known as OCT4) protein and significantly altered the
      expression of many genes that orchestrate cell morphogenesis during
      differentiation. The induction of cellular pluripotency in somatic cells was
      substantially impeded by the shRNA-mediated suppression of ST6GAL1, partially
      through interference with the expression of endogenous POU5F1 and SOX2. Targeting
      ST6GAL1 activity with a sialyltransferase inhibitor during cell reprogramming
      resulted in a dose-dependent reduction in the generation of human induced
      pluripotent stem cells (hiPSCs). Collectively, our data indicate that ST6GAL1
      plays an important role in the regulation of pluripotency and differentiation in
      hPSCs, and the pluripotent state in human cells can be modulated using
      pharmacological tools to target sialyltransferase activity. 

PMID- 26304833
TI  - Bile acids induce hepatic differentiation of mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSC) have the potential to differentiate into multiple
      cell lineages and their therapeutic potential has become obvious. In the liver,
      MSC are represented by stellate cells which have the potential to differentiate
      into hepatocytes after stimulation with growth factors. Since bile acids can
      promote liver regeneration, their influence on liver-resident and bone marrow
      derived MSC was investigated. Physiological concentrations of bile acids such as
      tauroursodeoxycholic acid were able to initiate hepatic differentiation of MSC
      via the farnesoid X receptor and transmembrane G-protein-coupled bile acid
      receptor 5 as investigated with knockout mice. Notch, hedgehog, transforming
      growth factor-beta/bone morphogenic protein family and non-canonical Wnt
      signalling were also essential for bile acid-mediated differentiation, whereas
      beta-catenin-dependent Wnt signalling was able to attenuate this process. Our
      findings reveal bile acid-mediated signalling as an alternative way to induce
      hepatic differentiaion of stem cells and highlight bile acids as important
      signalling molecules during liver regeneration. 

PMID- 26304834
TI  - Physiological Functions and Regulation of the Na+/H+ Exchanger [NHE1] in Renal
      Tubule Epithelial Cells.
AB  - The sodium-hydrogen exchanger isoform-1 [NHE1] is a ubiquitously expressed plasma
      membrane protein that plays a central role in intracellular pH and cell volume
      homeostasis by catalyzing an electroneutral exchange of extracellular sodium and
      intracellular hydrogen. Outside of this important physiological function, the
      NHE1 cytosolic tail domain acts as a molecular scaffold regulating cell survival
      and actin cytoskeleton organization through NHE1-dependent signaling proteins.
      NHE1 plays main roles in response to physiological stress conditions which in
      addition to cell shrinkage and acidification, include hypoxia and mechanical
      stimuli, such as cell stretch. NHE1-mediated modulation of programmed cell death
      results from the exchanger-mediated changes in pHi, cell volume, and/or [Na+]I;
      and, it has recently become known that regulation of cellular signaling pathways
      are involved as well. This review focuses on NHE1 functions and regulations. We
      describe evidence showing how these structural actions integrate with ion
      translocation in regulating renal tubule epithelial cell survival. 

PMID- 26304835
TI  - Quantification of Listeria monocytogenes cells with digital PCR and their biofilm
      cells with real-time PCR.
AB  - The purpose of this study was to develop a PCR-based method for quantification of
      Listeria monocytogenes adhesion in microtitre plates. We optimized isolation of
      DNA in the microtitre plates using cell lysis, ultrasound treatment, heating, and
      centrifugation of the lysate. Digital PCR was applied for quantification of L.
      monocytogenes DNA that was used for construction of the standard curve, and real
      time PCR was used for quantification of the attached L. monocytogenes cells. This
      PCR-based method was applied to quantify different strains of L. monocytogenes at
      different times of biofilm formation, and to study the anti-adhesive actions of
      natural bioactive substances (epigallocatechin gallate, (-)-alpha-pinene). The
      results show that the PCR-based method developed here can be widely used as a
      novel approach for adhesion assays and biofilm research. 

PMID- 26304836
TI  - Deletion of HAPS_2096 Increases Sensitivity to Cecropin B in Haemophilus
      parasuis.
AB  - Cecropin B (CB) is a very effective natural antimicrobial peptide that has shown
      great potential for future antimicrobial drug development. HAPS_2096 is a
      Haemophilus parasuis gene that encodes the periplasmic substrate-binding protein
      of an ATP-binding cassette-type amino acid transporter. In this research, we
      constructed and verified an HAPS_2096 deletion mutant and a complementary
      HAPS_2096 mutant of H. parasuis JS0135. A bactericidal assay revealed that the
      HAPS_2096 deletion mutant was significantly more sensitive than the wild-type
      strain to 0.25-0.5 ug/ml CB. However, the gene complementation alleviated the CB
      sensitivity of the mutant. Immunoelectron microscopy observation following a 30
      min treatment with a sublethal concentration of CB (0.25 MUg/ml) revealed more
      extensive morphological damage in the mutant strain than in the wild-type strain.
      Hence, our results suggest that the HAPS_2096 gene contributes to H. parasuis
      resistance to CB.

PMID- 26304838
TI  - Questioning causal involvement of telomeres in aging.
AB  - Multiple studies have demonstrated that telomere length predicts mortality and
      that telomeres shorten with age. Although rarely acknowledged these associations
      do not dictate causality. I review telomerase knockout and overexpression studies
      and find little support that telomeres cause aging. In addition, the causality
      hypothesis assumes that there is a critical telomere length at which senescence
      is induced. This generates the prediction that variance in telomere length
      decreases with age. In contrast, using meta-analysis of human data, I find no
      such decline. Inferring the causal involvement of telomeres in aging from current
      knowledge is therefore speculative and could hinder scientific progress. 

PMID- 26304839
TI  - Functional Characterization Reveals Novel Putative Coding Sequences in Prevotella
      ruminicola Genome Extracted from Rumen Metagenomic Studies.
AB  - AIM: To reassemble Prevotella ruminicola genome from rumen metagenomic data of
      cattle and buffalo and compare with the published reference genome. METHOD: Rumen
      microbial communities from Mehsani buffaloes (n = 8) and Kankrej cattle (n = 8),
      each adapted to different proportions of a dry or green roughage diet, were
      subjected to metagenomic sequencing by Ion Torrent PGM, and subsequent reads were
      analyzed by MG-RAST. Using reference-guided assembly of the sequences against the
      published P. ruminicola strain 23, draft genomes of 2.56 and 2.46 Mb were
      reconstructed from Mehsani buffalo and Kankrej cows, respectively. The genomes
      were annotated using the RAST Server and carbohydrate active enzyme (CAZyme)
      analysis. RESULTS: Taxonomic analysis by MG-RAST revealed P. ruminicola to be the
      most abundant species present among the rumen microflora. Functional annotation
      of reconstructed genomes using the RAST Server depicted the maximum assignment of
      coding sequences involved in the subsystems amino acid and derivatives and
      carbohydrate metabolism. CAZyme profiling revealed the glycoside hydrolases (GH)
      family to be the most abundant. GH family subclassification revealed that the
      extracted genomes had more sequence hits for GH2, GH3, GH92 and GH97 as compared
      to the reference. CONCLUSION: The results reflect the metabolic significance of
      rumen-adapted P. ruminicola in utilizing a coarse diet for animals based on
      acquisition of novel genetic elements.

PMID- 26304837
TI  - A research agenda for aging in China in the 21st century.
AB  - China is encountering formidable healthcare challenges brought about by the
      problem of aging. By 2050, there will be 400 million Chinese citizens aged 65+,
      150 million of whom will be 80+. The undesirable consequences of the one-child
      policy, rural-to-urban migration, and expansion of the population of 'empty nest'
      elders are eroding the traditional family care of the elders, further
      exacerbating the burden borne by the current public healthcare system. The
      challenges of geriatric care demand prompt attention by proposing strategies for
      improvement in several key areas. Major diseases of the elderly that need more
      attention include chronic non-communicable diseases and mental health disorders.
      We suggest the establishment of a home care-dominated geriatric care system, and
      a proactive role for researchers on aging in reforming geriatric care through
      policy dialogs. We propose ideas for preparation of the impending aging burden
      and the creation of a nurturing environment conducive to healthy aging in China.

PMID- 26304841
TI  - Discrepancy between femoral and capillary blood flow kinetics during knee
      extension exercise.
AB  - Capillary blood flow (QCAP) kinetics have previously been shown to be
      significantly slower than femoral artery (QFA) kinetics following the onset of
      dynamic knee extension exercise. If the increase in QCAP does not follow a
      similar time course to QFA, then a substantial proportion of the available blood
      flow is not distributed to the working muscle. One possible explanation for this
      discrepancy is that blood flow also increases to the nonworking lower leg
      muscles. Therefore, the present study aimed to determine if a reduction in lower
      limb blood flow, via arterial occlusion below the knee, alters the kinetics of
      QFA and QCAP during knee extension exercise, and thus provide insight into the
      potential mechanisms controlling the rapid increase in QFA. Subjects performed a
      ramp max test to determine the work rate at which gas exchange threshold (GET)
      occurred. At least four constant work rate trials with and without below-knee
      occlusion were conducted at work rates eliciting ~ 80% GET. Pulmonary gas
      exchange, near-infrared spectroscopy and QFA measurements were taken continuously
      during each exercise bout. Muscle oxygen uptake (VO2m) and
      deoxy[hemoglobin+myoglobin] were used to estimate QCAP. There was no significant
      difference between the uncuffed and cuffed conditions in any response (P>0.05).
      The mean response times (MRT) of QFA were 18.7 +/- 14.2s (uncuffed) and 24.6 +/-
      14.9s (cuffed). QCAP MRTs were 51.8 +/- 23.4s (uncuffed) and 56.7 +/- 23.2s
      (cuffed), which were not significantly different from the time constants (tau) of
      VO2m (39.7 +/- 23.2s (uncuffed) and 46.3 +/- 24.1s (cuffed). However, the MRT of
      QFA was significantly faster (P<0.05) than the MRT of QCAP and tauVO2m. tauVO2m
      and MRT QCAP were significantly correlated and estimated QCAP kinetics tracked
      VO2m following exercise onset. Cuffing below the knee did not significantly
      change the kinetics of QFA, QCAP or VO2m, although an effect size of 1.02
      suggested that a significant effect on QFA may have been hidden by small subject
      number.

PMID- 26304842
TI  - A Commentary on the Standards of Reporting of Neurological Disorders Checklist: A
      Guideline for the Reporting of Descriptive Studies in Neuroepidemiology.

PMID- 26304840
TI  - The role of depression chronicity and recurrence on neurocognitive dysfunctions
      in HIV-infected adults.
AB  - Research assessing whether major depressive disorders (MDD) impacts
      neurocognitive functions in HIV+ persons has yielded inconsistent results.
      However, none have considered the role of MDD remission, chronicity, and
      stability on treatment. Ninety-five HIV+ adults clinically stable on combined
      antiretroviral treatment completed a psychiatric interview, a depression scale, a
      neuropsychological, daily living, and cognitive complaints assessments at
      baseline and 18 months. Participants were screened for current (within 12 months
      of study entry) alcohol and/or substance use disorder. History of alcohol and/or
      substance abuse disorder prior to the 12 months entry screen and MDD treatments
      were recorded. Participants were grouped into two psychiatric nomenclatures: (1)
      lifetime: no MD episode (MDE), single MDE life-event treated and fully remitted,
      chronic MDD treated and stable, chronic MDD treated and unstable, and baseline
      untreated MDE; (2) recent: last 2 years MDE (yes or no). We found that lifetime
      and recent psychiatric history were more strongly associated with decreased in
      independence in daily living and cognitive complaints than with baseline
      neuropsychological performance. However, lack of full remission, instability on
      treatment in chronic MDD, and severity of symptoms in current MDE were factors in
      whether MDD impacted baseline neuropsychological performance. Depressive symptoms
      improved at follow-up in those with baseline moderate-severe symptoms, and MDD
      was not associated with neurocognitive change at 18 months. A history of alcohol
      and/or substance abuse disorder was significantly more frequent in those with
      treated and unstable chronic MDD but it was not associated with
      neuropsychological performance. MDD recurrence, chronicity profiles, and
      associated comorbidities are keys factors to understand any potential impact on
      neurocognitive abilities in HIV infection. More comprehensive consideration of
      these complex effects could serve at constructively updating the HAND diagnostic
      criteria. 

PMID- 26304843
TI  - Spontaneous prospective-memory processing: Unexpected fluency experiences trigger
      erroneous intention executions.
AB  - Event-based prospective memory is the ability to remember to execute an intention
      when an environmental cue occurs. It has been argued that, due to their special
      meaning, these cues are discrepant from their environment and therefore are
      sometimes spontaneously noticed. In line with this assumption, the likelihood
      that an intention will be executed increases with increased cue-discrepancy. It
      is not yet clear, however, whether these improvements are due to facilitated
      spontaneous noticing rather than to an increase in the efficiency of controlled
      cue-processing. To further investigate the spontaneous nature of cue-discrepancy
      benefits, we presented participants with stimuli that were unrelated to the
      intention but discrepant from other stimuli. Therefore, we experimentally
      increased the processing fluency of some stimuli for participants currently
      holding an intention by using different priming procedures. We found that stimuli
      whose fluency was increased via spaced repeated stimulus presentation (Experiment
      1) or via short pre-exposure (Experiment 2a to 3) elicited a tendency to fulfill
      the intention despite its actual inappropriateness. Findings were inconsistent as
      to whether cue-memory uncertainty fosters the reliance on cue discrepancy for
      intention retrieval (Experiments 2a and 3). Taken together, the present findings
      provide converging evidence for a spontaneous discrepancy-based prospective
      memory process which works independent of controlled processes. 

PMID- 26304845
TI  - Africans in the American Labor Market.
AB  - The number of migrants to the United States from Africa has grown exponentially
      since the 1930s. For the first time in America's history, migrants born in Africa
      are growing at a faster rate than migrants from any other continent. The
      composition of African-origin migrants has also changed dramatically: in the mid
      twentieth century, the majority were white and came from only three countries;
      but today, about one-fifth are white, and African-origin migrants hail from
      across the entire continent. Little is known about the implications of these
      changes for their labor market outcomes in the United States. Using the 2000-2011
      waves of the American Community Survey, we present a picture of enormous
      heterogeneity in labor market participation, sectoral choice, and hourly earnings
      of male and female migrants by country of birth, race, age at arrival in the
      United States, and human capital. For example, controlling a rich set of human
      capital and demographic characteristics, some migrants-such as those from South
      Africa/Zimbabwe and Cape Verde, who typically enter on employment visas-earn
      substantial premiums relative to other African-origin migrants. These premiums
      are especially large among males who arrived after age 18. In contrast, other
      migrants-such as those from Sudan/Somalia, who arrived more recently, mostly as
      refugees-earn substantially less than migrants from other African countries.
      Understanding the mechanisms generating the heterogeneity in these outcomes
      including levels of socioeconomic development, language, culture, and quality of
      education in countries of origin, as well as selectivity of those who migrate
      figures prominently among important unresolved research questions. 

PMID- 26304846
TI  - 5-Fluorouracil "Chemowraps" in the Treatment of Multiple Actinic Keratoses: A
      Norwich Experience.
AB  - INTRODUCTION: Topical 5-fluorouracil (5-FU) has been used to treat actinic
      keratosis for decades. It has been an important and effective treatment which the
      patient can self-administer, but is limited by the surface area of skin to be
      treated (according to the manufacturer's guidelines) of 500 cm(2). Other topical
      treatments can be painful, or require hospital/health care professional input.
      The use of 5-FU under occlusion (chemowraps) for large areas of sun-damaged skin
      on the arms or legs has been described and is a potentially useful treatment
      option. We describe our experiences with this technique in the Norfolk and
      Norwich University Hospital Dermatology Department (Norwich, UK). METHODS: Five
      patients were recruited into this pilot study. Topical 5-FU was applied to sun
      damaged limbs under occlusion, and reviewed weekly for response, and local or
      systemic side effects. Treatment duration was 12-14 weeks. Clinical photography
      was undertaken prior to, during, and after treatment to document response.
      RESULTS: We show that there was substantial clinical improvement in the treated
      skin in our patients. Experienced dermatologists reviewed all the patients, and
      documented the changes photographically, and by counting lesions. All patients
      were satisfied with their treatment regimen, and also with the end result;
      although two did not complete the treatment regimen due to complications not
      directly attributable to the treatment. CONCLUSION: Topical 5-FU under occlusion
      (chemowraps) may be a valid treatment option for large areas of sun-damaged skin
      with field cancerization changes, due to low systemic and local toxicity, and
      acceptability to patients.

PMID- 26304844
TI  - Phenotyping Stroke in Sub-Saharan Africa: Stroke Investigative Research and
      Education Network (SIREN) Phenomics Protocol.
AB  - BACKGROUND: As the second leading cause of death and the leading cause of adult
      onset disability, stroke is a major public health concern particularly pertinent
      in Sub-Saharan Africa (SSA), where nearly 80% of all global stroke mortalities
      occur, and stroke burden is projected to increase in the coming decades. However,
      traditional and emerging risk factors for stroke in SSA have not been well
      characterized, thus limiting efforts at curbing its devastating toll. The Stroke
      Investigative Research and Education Network (SIREN) project is aimed at
      comprehensively evaluating the key environmental and genomic risk factors for
      stroke (and its subtypes) in SSA while simultaneously building capacities in
      phenomics, biobanking, genomics, biostatistics, and bioinformatics for brain
      research. METHODS: SIREN is a transnational, multicentre, hospital and community
      based study involving 3,000 cases and 3,000 controls recruited from 8 sites in
      Ghana and Nigeria. Cases will be hospital-based patients with first stroke within
      10 days of onset in whom neurovascular imaging will be performed. Etiological and
      topographical stroke subtypes will be documented for all cases. Controls will be
      hospital- and community-based participants, matched to cases on the basis of
      gender, ethnicity, and age (+/-5 years). Information will be collected on known
      and proposed emerging risk factors for stroke. STUDY SIGNIFICANCE: SIREN is the
      largest study of stroke in Africa to date. It is anticipated that it will shed
      light on the phenotypic characteristics and risk factors of stroke and ultimately
      provide evidence base for strategic interventions to curtail the burgeoning
      burden of stroke on the sub-continent.

PMID- 26304847
TI  - Waiting time distribution in public health care: empirics and theory.
AB  - Excessive waiting times for elective surgery have been a long-standing concern in
      many national healthcare systems in the OECD. How do the hospital admission
      patterns that generate waiting lists affect different patients? What are the
      hospitals characteristics that determine waiting times? By developing a model of
      healthcare provision and analysing empirically the entire waiting time
      distribution we attempt to shed some light on those issues. We first build a
      theoretical model that describes the optimal waiting time distribution for
      capacity constraint hospitals. Secondly, employing duration analysis, we obtain
      empirical representations of that distribution across hospitals in the UK from
      1997-2005. We observe important differences on the 'scale' and on the 'shape' of
      admission rates. Scale refers to how quickly patients are treated and shape
      represents trade-offs across duration-treatment profiles. By fitting the
      theoretical to the empirical distributions we estimate the main structural
      parameters of the model and are able to closely identify the main drivers of
      these empirical differences. We find that the level of resources allocated to
      elective surgery (budget and physical capacity), which determines how constrained
      the hospital is, explains differences in scale. Changes in benefits and costs
      structures of healthcare provision, which relate, respectively, to the desire to
      prioritise patients by duration and the reduction in costs due to delayed
      treatment, determine the shape, affecting short and long duration patients
      differently. JEL Classification I11; I18; H51. 

PMID- 26304848
TI  - SENESCENCE-SUPPRESSED PROTEIN PHOSPHATASE Directly Interacts with the Cytoplasmic
      Domain of SENESCENCE-ASSOCIATED RECEPTOR-LIKE KINASE and Negatively Regulates
      Leaf Senescence in Arabidopsis.
AB  - Reversible protein phosphorylation mediated by protein kinases and phosphatases
      plays an important role in the regulation of leaf senescence. We previously
      reported that the leucine-rich repeat receptor-like kinase SENESCENCE-ASSOCIATED
      RECEPTOR-LIKE KINASE (AtSARK) positively regulates leaf senescence in Arabidopsis
      (Arabidopsis thaliana). Here, we report the involvement of a protein
      serine/threonine phosphatase 2C-type protein phosphatase, SENESCENCE-SUPPRESSED
      PROTEIN PHOSPHATASE (SSPP), in the negative regulation of Arabidopsis leaf
      senescence. SSPP transcript levels decreased greatly during both natural
      senescence and SARK-induced precocious senescence. Overexpression of SSPP
      significantly delayed leaf senescence in Arabidopsis. Protein pull-down and
      bimolecular fluorescence complementation assays demonstrated that the cytosol
      localized SSPP could interact with the cytoplasmic domain of the plasma membrane
      localized AtSARK. In vitro assays showed that SSPP has protein phosphatase
      function and can dephosphorylate the cytosolic domain of AtSARK. Consistent with
      these observations, overexpression of SSPP effectively rescued AtSARK-induced
      precocious leaf senescence and changes in hormonal responses. All our results
      suggested that SSPP functions in sustaining proper leaf longevity and preventing
      early senescence by suppressing or perturbing SARK-mediated senescence signal
      transduction. 

PMID- 26304849
TI  - Phosphorylation and Dephosphorylation of the Presequence of Precursor MULTIPLE
      ORGANELLAR RNA EDITING FACTOR3 during Import into Mitochondria from Arabidopsis.
AB  - The nucleus-encoded mitochondria-targeted proteins, multiple organellar RNA
      editing factors (MORF3, MORF5, and MORF6), interact with Arabidopsis (Arabidopsis
      thaliana) PURPLE ACID PHOSPHATASE2 (AtPAP2) located on the chloroplast and
      mitochondrial outer membranes in a presequence-dependent manner. Phosphorylation
      of the presequence of the precursor MORF3 (pMORF3) by endogenous kinases in wheat
      germ translation lysate, leaf extracts, or STY kinases, but not in rabbit
      reticulocyte translation lysate, resulted in the inhibition of protein import
      into mitochondria. This inhibition of import could be overcome by altering
      threonine/serine residues to alanine on the presequence, thus preventing
      phosphorylation. Phosphorylated pMORF3, but not the phosphorylation-deficient
      pMORF3, can form a complex with 14-3-3 proteins and HEAT SHOCK PROTEIN70. The
      phosphorylation-deficient mutant of pMORF3 also displayed faster rates of import
      when translated in wheat germ lysates. Mitochondria isolated from plants with
      altered amounts of AtPAP2 displayed altered protein import kinetics. The import
      rate of pMORF3 synthesized in wheat germ translation lysate into pap2
      mitochondria was slower than that into wild-type mitochondria, and this rate
      disparity was not seen for pMORF3 synthesized in rabbit reticulocyte translation
      lysate, the latter translation lysate largely deficient in kinase activity. Taken
      together, these results support a role for the phosphorylation and
      dephosphorylation of pMORF3 during the import into plant mitochondria. These
      results suggest that kinases, possibly STY kinases, and AtPAP2 are involved in
      the import of protein into both mitochondria and chloroplasts and provide a
      mechanism by which the import of proteins into both organelles may be
      coordinated. 

PMID- 26304850
TI  - The Calcium Ion Is a Second Messenger in the Nitrate Signaling Pathway of
      Arabidopsis.
AB  - Understanding how plants sense and respond to changes in nitrogen availability is
      the first step toward developing strategies for biotechnological applications,
      such as improvement of nitrogen use efficiency. However, components involved in
      nitrogen signaling pathways remain poorly characterized. Calcium is a second
      messenger in signal transduction pathways in plants, and it has been indirectly
      implicated in nitrate responses. Using aequorin reporter plants, we show that
      nitrate treatments transiently increase cytoplasmic Ca(2+) concentration. We
      found that nitrate also induces cytoplasmic concentration of inositol 1,4,5
      trisphosphate. Increases in inositol 1,4,5-trisphosphate and cytoplasmic Ca(2+)
      levels in response to nitrate treatments were blocked by U73122, a
      pharmacological inhibitor of phospholipase C, but not by the nonfunctional
      phospholipase C inhibitor analog U73343. In addition, increase in cytoplasmic
      Ca(2+) levels in response to nitrate treatments was abolished in mutants of the
      nitrate transceptor NITRATE TRANSPORTER1.1/Arabidopsis (Arabidopsis thaliana)
      NITRATE TRANSPORTER1 PEPTIDE TRANSPORTER FAMILY6.3. Gene expression of nitrate
      responsive genes was severely affected by pretreatments with Ca(2+) channel
      blockers or phospholipase C inhibitors. These results indicate that Ca(2+) acts
      as a second messenger in the nitrate signaling pathway of Arabidopsis. Our
      results suggest a model where NRT1.1/AtNPF6.3 and a phospholipase C activity
      mediate the increase of Ca(2+) in response to nitrate required for changes in
      expression of prototypical nitrate-responsive genes. 

PMID- 26304851
TI  - Effects of strontium ranelate on markers of cardiovascular risk in postmenopausal
      osteoporotic women.
AB  - Recent pooled analyses have shown that strontium ranelate increases the incidence
      of venous thromboembolism and non-fatal myocardial infarction, but no
      explanations were given. The aim of our study was to assess the effects a 12
      month treatment with strontium ranelate on hemostasis factors and markers of
      cardiovascular risk in postmenopausal osteoporotic women. Forty osteoporotic
      postmenopausal women received orally strontium ranelate 2 g daily, plus calcium
      and colecalcipherol for 12 months. Forty postmenopausal osteopenic women matched
      for age, menopausal age, and body mass index served as controls and received
      orally calcium and colecalcipherol for 12 months. Biochemical cardiovascular risk
      factors and hemostatic indices were assayed prior to treatment, and after 3, 6,
      and 12 months of therapy. These indices included fibrinogen, fasting glucose,
      total serum cholesterol, high-density lipoprotein cholesterol, low-density
      lipoprotein cholesterol, triglycerides, plasma levels of D-dimer, homocysteine,
      partial thromboplastin time, and prothrombin time. In addition, we evaluated
      possible changes in blood pressure and occurrence of venous thromboembolic
      events. At baseline, no statistically significance was observed between the two
      groups except for bone mineral density at lumbar spine, femoral neck, and total
      femur, which was lower in strontium ranelate group. After 12 months of treatment,
      there was no statistically significant change in cardiovascular risk factors and
      hemostatic parameters. None of the 40 women developed any clinical venous
      thromboembolic event. A 12-month treatment with strontium ranelate did not alter
      hemostasis factors or markers of cardiovascular risk, suggesting that reported
      increased risk of venous thromboembolism and myocardial infarction with strontium
      is mediated by other factors. 

PMID- 26304852
TI  - Analysis of Amyloid in Medullary Thyroid Carcinoma by Mass Spectrometry-Based
      Proteomic Analysis.
AB  - Amyloid is a characteristic histologic feature in medullary thyroid carcinomas
      (MTC). We utilized a novel mass spectrometry-based proteomic analysis to
      determine if we could identify specific proteins associated with amyloid in MTC.
      We studied 9 MTC (1 multiple endocrine neoplasia type 2A, 1 familial MTC, and 7
      sporadic). Laser microdissection was utilized to sample the amyloid which was
      then trypsin digested and evaluated by liquid chromatography electrospray tandem
      MS (LC-MS/MS) which identified the presence of amyloidogenic proteins in all
      cases of MTC. High levels of calcitonin were identified in all 9 cases of MTC.
      Secretogranin-1 was identified in 6 of 9 MTC. Calcitonin gene-related peptide was
      identified in 4 of 9 cases of MTC. LC-MS/MS proteomic analysis provides a rapid,
      highly specific, and sensitive method for identification of the specific type of
      amyloid in these endocrine tumors. This approach may allow classification of
      different forms of endocrine amyloid present in neuroendocrine tumors. 

PMID- 26304853
TI  - Unfolded Protein Response Pathways in Neurodegenerative Diseases.
AB  - The aggregation of disease-specific misfolded proteins resulting in endoplasmic
      reticulum stress is associated with early pathological events in many
      neurodegenerative diseases, and apoptotic signaling is initiated when the stress
      goes beyond the maximum threshold level of endoplasmic reticulum stress sensors.
      All eukaryotic cells respond to the accumulation of unfolded proteins in the
      endoplasmic reticulum (ER) by signaling an adaptive pathway termed as unfolded
      protein response (UPR). Recently, the focus of research shifted from work on
      specific proteins as pathogenesis in these neurodegenerative diseases towards a
      more specific generic pathway known as UPR. ER is a major organelle for protein
      quality control, and cellular stress disrupts normal functioning of ER. The UPR
      acts as a protective mechanism during endoplasmic reticulum stress, but
      persistent long-term stress triggers UPR-mediated apoptotic pathways ultimately
      leading to cell death. Here in this review, we will briefly summarize the
      molecular events of endoplasmic reticulum stress-associated UPR signaling
      pathways and their potential therapeutic role in neurodegenerative diseases. 

PMID- 26304854
TI  - Concurrent radiotherapy with S-1 plus cisplatin versus concurrent radiotherapy
      with cisplatin alone for the treatment of locally advanced cervical carcinoma: a
      pilot randomised controlled trial.
AB  - BACKGROUND: In the present study, we compared the efficacy and safety of
      concurrent radiotherapy with S-1 plus cisplatin (CRSC) versus concurrent
      radiotherapy with cisplatin alone (CRC) for the treatment of advanced cervical
      carcinoma (ACC). METHODS: Between February 2006 and January 2009, 72 eligible
      patients with ACC were included and randomly divided into two groups. Thirty-six
      patients received CRSC with radiotherapy (60 Gy/30 fractions over 6 weeks)
      beginning on day 1, S-1 (according to body surface area) for 28 days repeated
      every 6 weeks, and cisplatin (50 mg/m(2), intravenously on day 1) every 4 weeks
      for two cycles. The other 36 received CRC at the same cisplatin and radiotherapy
      dosage as for CRSC. The primary outcome was overall survival, whereas the
      secondary outcomes included progression-free survival and toxicity. RESULTS: The
      median overall survival was 75 months (range 4-86 months) for the CRSC group and
      66 months (range 3-87 months) for the CRC group (P = 0.039). The median
      corresponding progression-free survival was 66 months (range 3-75 months) and 58
      months (range 3-71 months), respectively (P = 0.042). The toxicity profile was
      similar in both the groups. CONCLUSION: Our results suggested that CRSC might be
      more effective than CRC in patients with ACC with acceptable toxicity.

PMID- 26304856
TI  - Cavernous Hemangioma of the External Canal, Tympanic Membrane, and Middle Ear
      Cleft: A Case Report.
AB  - Cavernous hemangioma involving the external canal, tympanic membrane, and middle
      ear cavity is extremely rare. We present a case of a 45-year-old woman who had
      progressive right sided decreased hearing, pulsatile tinnitus, and aural fullness
      of 7 months duration. Microscopic examination, imaging studies, surgical
      treatment, and histological evaluation are reported. To the best of our
      knowledge, this is the first case of cavernous hemangioma with simultaneous
      involvement of the external ear, tympanic membrane, middle ear, and attic
      reported in English literature.

PMID- 26304855
TI  - The effect of exogenous calcium on mitochondria, respiratory metabolism enzymes
      and ion transport in cucumber roots under hypoxia.
AB  - Hypoxia induces plant stress, particularly in cucumber plants under hydroponic
      culture. In plants, calcium is involved in stress signal transmission and growth.
      The ultimate goal of this study was to shed light on the mechanisms underlying
      the effects of exogenous calcium on the mitochondrial antioxidant system, the
      activity of respiratory metabolism enzymes, and ion transport in cucumber
      (Cucumis sativus L. cv. Jinchun No. 2) roots under hypoxic conditions. Our
      experiments revealed that exogenous calcium reduces the level of reactive oxygen
      species (ROS) and increases the activity of antioxidant enzymes in mitochondria
      under hypoxia. Exogenous calcium also enhances the accumulation of enzymes
      involved in glycolysis and the tricarboxylic acid (TCA) cycle. We utilized
      fluorescence and ultrastructural cytochemistry methods to observe that exogenous
      calcium increases the concentrations of Ca(2+) and K(+) in root cells by
      increasing the activity of plasma membrane (PM) H(+)-ATPase and tonoplast H(+)
      ATPase and H(+)-PPase. Overall, our results suggest that hypoxic stress has an
      immediate and substantial effect on roots. Exogenous calcium improves metabolism
      and ion transport in cucumber roots, thereby increasing hypoxia tolerance in
      cucumber. 

PMID- 26304857
TI  - Latino Cigarette Smoking Patterns by Gender in a US-National Sample.
AB  - BACKGROUND: Latino smokers are a rising public health concern who experience
      elevated tobacco-related health disparities. PURPOSE: Additional information on
      Latino smoking is needed to inform screening and treatment. ANALYSIS: Latent
      class analysis using smoking frequency, cigarette preferences, onset, smoking
      duration, cigarettes per day, and minutes to first cigarette was used to create
      multivariate latent smoking profiles for Latino men and women. RESULTS: Final
      models found seven classes for Latinas and nine classes for Latinos. Despite a
      common finding in the literature that Latino smokers are more likely to be low
      risk intermittent smokers, the majority of classes for both males and females
      described patterns of high-risk daily smoking. Gender variations in smoking
      classes were noted. CONCLUSIONS: Several markers of smoking risk were identified
      among both male and female Latino smokers, including long durations of smoking,
      daily smoking, and preference for specialty cigarettes, all factors associated
      with long-term health consequences.

PMID- 26304858
TI  - Unplanned 3-day re-attendance rate at Emergency Department (ED) and hospital's
      bed occupancy rate (BOR).
AB  - BACKGROUND: Unplanned re-attendance at the Emergency Department (ED) is often
      monitored as a quality indicator of the care accorded to patients during their
      index ED visit. High bed occupancy rate (BOR) has been considered as a matter of
      reduced patient comfort and privacy. Most hospitals in Singapore operate under
      BORs above 85 %. This study aims to explore factors associated with the unplanned
      3-day ED re-attendance rate and, in particular, if higher BOR is associated with
      higher 3-day unplanned ED re-attendance rate. METHODS: This was a multicenter
      retrospective study using time series data. Three acute tertiary hospitals were
      selected from all six adult public hospitals in Singapore based on data
      availability. Daily data from year 2008 to 2013 were collected from the study
      hospitals' information systems. These included: ED visit date, day of week,
      month, year, public holiday, daily hospital BOR, daily bed waiting time (BWT) at
      ED (both median and 95th percentile), daily ED admission rate, and 3-day ED re
      attendance rate. The primary outcome of the study was unplanned 3-day ED re
      attendance rate from all reasons. Both univariate analysis and generalized linear
      regression were respectively applied to study the crude and adjusted association
      between the unplanned 3-day ED re-attendance rate and its potential associated
      factors. All analyses were conducted using SPSS 18 (PASW 18, IBM). RESULTS: The
      average age of patients who visited ED was 35 years old (SD = 2), 37 years old
      (SD = 2), and 40 years old (SD = 2) in hospitals A, B, and C respectively. The
      average 3-day unplanned ED re-attendance rate was 4.9 % (SE = 0.47 %) in hospital
      A, 3.9 % (SE = 0.35 %) in hospital B, and 4.4 % (SE = 0.30 %) in hospital C.
      After controlling for other covariates, the unplanned 3-day ED re-attendance
      rates were significantly associated with hospital, time trend, day of week, daily
      average BOR, and ED admission rate. Strong day-of-week effect on early ED re
      attendance rate was first explored in this study. Thursday had the lowest re
      attendance rate, while Sunday has the highest re-attendance rate. The patients
      who visited at ED on the dates with higher BOR were more likely to re-attend the
      ED within 3 days for hospitals A and B. There was no significant association
      between BOR and ED re-attendance rate in hospital C. CONCLUSIONS: A study using
      time series data has been conducted to explore the factors associated with the
      unplanned 3-day ED re-attendance rate. Strong day-of-week effect was first
      reported. The association between BOR and the ED re-attendance rate varied with
      hospital.

PMID- 26304859
TI  - 2D-Cosy NMR Spectroscopy as a Quantitative Tool in Biological Matrix: Application
      to Cyclodextrins.
AB  - Classical analytical quantifications in biological matrices require time
      consuming sample pre-treatments and extractions. Nuclear magnetic resonance (NMR)
      analysis does not require heavy sample treatments or extractions which therefore
      increases its accuracy in quantification. In this study, even if quantitative
      (q)NMR could not be applied to 2D spectra, we demonstrated that cross
      correlations and diagonal peak intensities have a linear relationship with the
      analyzed pharmaceutical compound concentration. This work presents the validation
      process of a 2D-correlation spectroscopy (COSY) NMR quantification of 2
      hydroxypropyl-beta-cyclodextrin in plasma. Specificity, linearity, precision
      (repeatability and intermediate precision), trueness, limits of quantification
      (LOQs), and accuracy were used as validation criteria. 2D-NMR could therefore be
      used as a valuable and accurate analytical technique for the quantification of
      pharmaceutical compounds, including hardly detectable compounds such as
      cyclodextrins or poloxamers, in complex biological matrices based on a
      calibration curve approach. 

PMID- 26304860
TI  - Cerebral Microbleeds and Thrombolysis-Associated Intracerebral Hemorrhage: Cause
      for Concern, or Just a Distraction?

PMID- 26304862
TI  - Recurrent Stroke: The Value of the CHA2DS2VASc Score and the Essen Stroke Risk
      Score in a Nationwide Stroke Cohort.
AB  - BACKGROUND AND PURPOSE: The CHA2DS2VASc score and the Essen Stroke Risk Score are
      respectively used for risk stratification in patients with atrial fibrillation
      and in patients with cerebrovascular incidents. We aimed to test the ability of
      the 2 scores to predict stroke recurrence, death, and cardiovascular events
      (stroke, transient ischemic attack, myocardial infarction, or arterial
      thromboembolism) in a nationwide Danish cohort study, among patients with
      incident ischemic stroke and no atrial fibrillation. METHODS: We conducted a
      registry-based study in patients with incident ischemic stroke and no atrial
      fibrillation. Patients were stratified according to the CHA2DS2VASc score and the
      Essen Stroke Risk Score and were followed up until stroke recurrence or death. We
      estimated stratified incidence rates and hazard ratios and calculated the
      cumulative risks. RESULTS: 42 182 patients with incident ischemic stroke with
      median age 70.1 years were included. The overall 1-year incidence rates of
      recurrent stroke, death, and cardiovascular events were 3.6%, 10.5%, and 6.7%,
      respectively. The incidence rates, the hazard ratios, and the cumulative risk of
      all outcomes increased with increasing risk scores. C-statistics for both risk
      scores were around 0.55 for 1-year stroke recurrence and cardiovascular events
      and correspondingly for death around 0.67 for both scores. CONCLUSIONS: In this
      cohort of non-atrial fibrillation patients with incident ischemic stroke,
      increasing CHA2DS2VASc score and Essen Stroke Risk Score was associated with
      increasing risk of recurrent stroke, death, and cardiovascular events. Their
      discriminatory performance was modest and further refinements are required for
      clinical application.

PMID- 26304863
TI  - Non-Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention in Asian
      Patients With Nonvalvular Atrial Fibrillation: Meta-Analysis.
AB  - BACKGROUND AND PURPOSE: The use of vitamin K antagonists (VKAs), the cornerstone
      treatment for stroke prevention in patients with atrial fibrillation, is limited
      by the perceived risk of serious bleeding in Asia. Non-VKA oral anticoagulants
      (NOACs) are safer alternatives. Here, we evaluate performance differences of
      NOACs between Asians and non-Asians. METHODS: We compared efficacy and safety of
      NOACs between patients enrolled in Asian and non-Asian countries using
      aggregative data from phase III clinical trials. The odds ratios (ORs [95%
      confidence interval]) were calculated by a random effects model. RESULTS:
      Comparing with VKAs, standard-dose NOACs reduced stroke or systemic embolism
      (OR=0.65 [0.52-0.83] versus 0.85 [0.77-0.93], P interaction= 0.045) more in
      Asians than in non-Asians and were safer in Asians than in non-Asians about major
      bleeding (OR=0.57 [0.44-0.74] versus 0.89 [0.76-1.04], P interaction=0.004),
      hemorrhagic stroke (OR=0.32 [0.19-0.52] versus 0.56 [0.44-0.70], P
      interaction=0.046) in particular, whereas gastrointestinal bleeding was
      significantly increased in non-Asians (OR=0.79 [0.48-1.32] versus 1.44 [1.12
      1.85], P interaction=0.041). Generally, low-dose NOACs were safer than VKAs
      without heterogeneity in efficacy and safety between Asians and non-Asians,
      except for ischemic stroke, major, and gastrointestinal bleeding. CONCLUSIONS:
      Our findings suggest that standard-dose NOACs were more effective and safer in
      Asians than in non-Asians, whereas low-dose NOACs performed similarly in both
      populations.

PMID- 26304865
TI  - Increase in [18F]-Fluoroacetate Uptake in Patients With Chronic Hemodynamic
      Cerebral Ischemia.
AB  - BACKGROUND AND PURPOSE: [18F]-fluoroacetate ((18)F-FACE) can be used for
      evaluating glial cell metabolism. Experimental studies have shown an increase in
      (18)F-FACE uptake in rodent models of cerebral ischemia. The aim of this study
      was to determine whether (18)F-FACE uptake is increased in the noninfarcted
      cerebral cortex in patients with hemodynamic ischemia owing to atherosclerotic
      internal carotid artery or middle cerebral artery disease. METHODS: We evaluated
      9 symptomatic patients with unilateral atherosclerotic internal carotid artery or
      middle cerebral artery disease and no cortical infarction using positron emission
      tomography with (18)F-FACE and (15)O-gases. (18)F-FACE uptake during 40 to 60
      minutes after injection was compared with the cerebral blood flow, cerebral
      metabolic rate of oxygen, oxygen extraction fraction, and cerebral blood volume
      in the middle cerebral artery distributions. RESULTS: Significant decreases of
      cerebral blood flow and cerebral metabolic rate of oxygen and increases of oxygen
      extraction fraction and cerebral blood volume were found in the hemisphere
      ipsilateral to the arterial lesion, and (18)F-FACE uptake in this region was
      greater than that in the contralateral hemisphere. The relative (18)F-FACE uptake
      (ipsilateral/contralateral ratio) was negatively correlated with cerebral blood
      flow or cerebral metabolic rate of oxygen values and was positively correlated
      with oxygen extraction fraction values. Multivariate analysis showed that the
      ipsilateral/contralateral (18)F-FACE uptake ratio was independently correlated
      with the cerebral blood flow (or oxygen extraction fraction) and cerebral
      metabolic rate of oxygen values. CONCLUSIONS: In patients with atherosclerotic
      internal carotid artery or middle cerebral artery disease, (18)F-FACE uptake is
      increased in the noninfarcted cerebral cortex with chronic hemodynamic ischemia
      characterized by misery perfusion with decreased oxygen metabolism. Increased
      (18)F-FACE uptake may indicate the cortical regions that are at particular risk
      for ischemic damage.

PMID- 26304864
TI  - Deferoxamine, Cerebrovascular Hemodynamics, and Vascular Aging: Potential Role
      for Hypoxia-Inducible Transcription Factor-1-Regulated Pathways.
AB  - BACKGROUND AND PURPOSE: Iron chelation therapy is emerging as a novel
      neuroprotective strategy. The mechanisms of neuroprotection are diverse and
      include both neuronal and vascular pathways. We sought to examine the effect of
      iron chelation on cerebrovascular function in healthy aging and to explore
      whether hypoxia-inducible transcription factor-1 activation may be temporally
      correlated with vascular changes. METHODS: We assessed cerebrovascular function
      (autoregulation, vasoreactivity, and neurovascular coupling) and serum
      concentrations of vascular endothelial growth factor and erythropoietin, as
      representative measures of hypoxia-inducible transcription factor-1 activation,
      during 6 hours of deferoxamine infusion in 24 young and 24 older healthy
      volunteers in a randomized, blinded, placebo-controlled cross-over study design.
      Cerebrovascular function was assessed using the transcranial Doppler ultrasound.
      Vascular endothelial growth factor and erythropoietin serum protein assays were
      conducted using the Meso Scale Discovery platform. RESULTS: Deferoxamine elicited
      a strong age- and time-dependent increase in the plasma concentrations of
      erythropoietin and vascular endothelial growth factor, which persisted <=3 hours
      post infusion (age effect P=0.04; treatment*time P<0.01). Deferoxamine infusion
      also resulted in a significant time- and age-dependent improvement in cerebral
      vasoreactivity (treatment*time P<0.01; age P<0.01) and cerebral autoregulation
      (gain: age*time*treatment P=0.04). CONCLUSIONS: Deferoxamine infusion improved
      cerebrovascular function, particularly in older individuals. The temporal
      association between improved cerebrovascular function and increased serum
      vascular endothelial growth factor and erythropoietin concentrations is
      supportive of shared hypoxia-inducible transcription factor-1-regulated pathways.
      Therefore, pharmacological activation of hypoxia-inducible transcription factor-1
      to enhance cerebrovascular function may be a promising neuroprotective strategy
      in acute and chronic ischemic syndromes, especially in elderly patients. CLINICAL
      TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier:
      NCT013655104.

PMID- 26304866
TI  - Dabigatran Therapy in Acute Ischemic Stroke Patients Without Atrial Fibrillation.
AB  - BACKGROUND AND PURPOSE: Acute ischemic stroke patients are at risk of early
      recurrence. We tested the feasibility and safety of initiating dabigatran in
      patients, within 24 hours of minor stroke in patients without atrial
      fibrillation. METHODS: Minor stroke patients (National Institutes of Health
      Stroke Scale score <=3) without atrial fibrillation and evidence of acute
      infarction on magnetic resonance imaging were treated with dabigatran. Treatment
      began within 24 hours of onset and was continued for 30 days. The primary end
      point was symptomatic hemorrhagic transformation. RESULTS: A total of 53 patients
      with median (interquartile range) age of 68 (57-77) years and National Institutes
      of Health Stroke Scale score of 1 (0-2) were enrolled. Baseline diffusion
      weighted imaging volume was 0.8 (0.3-2.4) mL. No patients experienced symptomatic
      hemorrhagic transformation. Three patients had evidence of asymptomatic petechial
      hemorrhagic transformation on day 7, which remained stable at day 30, while
      continuing dabigatran. CONCLUSIONS: Dabigatran treatment within 24 hours of minor
      stroke is feasible. A larger randomized trial is required to confirm the safety
      and efficacy of this treatment approach. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT 01769703.

PMID- 26304867
TI  - Minimally Invasive Microsurgery for Cerebral Aneurysms.

PMID- 26304868
TI  - Organizational Update: Report From the European Stroke Organisation 2015.

PMID- 26304869
TI  - Correction.

PMID- 26304870
TI  - Correction.

PMID- 26304871
TI  - Impact of Precision Medicine in Diverse Cancers: A Meta-Analysis of Phase II
      Clinical Trials.
AB  - PURPOSE: The impact of a personalized cancer treatment strategy (ie, matching
      patients with drugs based on specific biomarkers) is still a matter of debate.
      METHODS: We reviewed phase II single-agent studies (570 studies; 32,149 patients)
      published between January 1, 2010, and December 31, 2012 (PubMed search).
      Response rate (RR), progression-free survival (PFS), and overall survival (OS)
      were compared for arms that used a personalized strategy versus those that did
      not. RESULTS: Multivariable analysis (both weighted multiple linear regression
      and random effects meta-regression) demonstrated that the personalized approach,
      compared with a nonpersonalized approach, consistently and independently
      correlated with higher median RR (31% v 10.5%, respectively; P < .001) and
      prolonged median PFS (5.9 v 2.7 months, respectively; P < .001) and OS (13.7 v
      8.9 months, respectively; P < .001). Nonpersonalized targeted arms had poorer
      outcomes compared with either personalized targeted therapy or cytotoxics, with
      median RR of 4%, 30%, and 11.9%, respectively; median PFS of 2.6, 6.9, and 3.3
      months, respectively (all P < .001); and median OS of 8.7, 15.9, and 9.4 months,
      respectively (all P < .05). Personalized arms using a genomic biomarker had
      higher median RR and prolonged median PFS and OS (all P <= .05) compared with
      personalized arms using a protein biomarker. A personalized strategy was
      associated with a lower treatment-related death rate than a nonpersonalized
      strategy (median, 1.5% v 2.3%, respectively; P < .001). CONCLUSION: Comprehensive
      analysis of phase II, single-agent arms revealed that, across malignancies, a
      personalized strategy was an independent predictor of better outcomes and fewer
      toxic deaths. In addition, nonpersonalized targeted therapies were associated
      with significantly poorer outcomes than cytotoxic agents, which in turn were
      worse than personalized targeted therapy.

PMID- 26304872
TI  - Trebananib (AMG 386) in Combination With Sunitinib in Patients With Metastatic
      Renal Cell Cancer: An Open-Label, Multicenter, Phase II Study.
AB  - PURPOSE: Trebananib, an investigational recombinant peptide-Fc fusion protein,
      neutralizes the receptor-ligand interaction between Tie2 and angiopoietin-1/2.
      This phase II study was conducted to evaluate trebananib plus sunitinib, a
      vascular endothelial growth factor receptor inhibitor, in patients with
      metastatic clear cell renal cell carcinoma. PATIENTS AND METHODS: Adults with
      metastatic renal cell carcinoma were enrolled sequentially onto two cohorts that
      received sunitinib 50 mg once per day for 4 weeks on and 2 weeks off and
      intravenous trebananib once per week at a dose of 10 mg/kg in cohort A or 15
      mg/kg in cohort B. The primary end points were incidences of adverse events (AEs)
      and dose interruptions of sunitinib during the first 12 weeks of treatment.
      Secondary end points included objective response rate and progression-free
      survival. RESULTS: Eighty-five patients were enrolled: 43 in cohort A, and 42 in
      cohort B. During the first 12 weeks of treatment, 58% and 57% of patients in
      cohorts A and B, respectively, had sunitinib dose interruptions (dose decrease,
      withholding, or withdrawal). The most frequent AEs were diarrhea (cohort A, 74%;
      cohort B, 67%), mucosal inflammation (cohort A, 49%; cohort B, 60%), and
      hypertension (cohort A, 52%; cohort B, 45%). AEs of grade 3 or greater occurred
      in 58% of patients in cohort A and in 69% of patients in cohort B. The objective
      response rate was 58% and 63% in cohorts A and B, respectively. The median
      progression-free survival time was 13.9 months (95% CI, 10.4 to 19.2) and 16.3
      months (95% CI, 13.1 to 21.4) in cohorts A and B, respectively. The median
      overall survival time was 36 months (95% CI, 25.2 to not estimable) in cohort A
      and was not estimable (median follow-up, 25 months) in cohort B. CONCLUSION:
      Trebananib plus sunitinib seemed to increase toxicity at the tested doses.
      Efficacy results suggest a potential benefit for the addition of trebananib to
      sunitinib.

PMID- 26304873
TI  - Management of Germ Cell Cancer: Lessons Learned From a National Database.

PMID- 26304876
TI  - Reply to A. Messori et al, R. Bordonaro et al, and G. Fasola et al.

PMID- 26304875
TI  - Electronic Trigger-Based Intervention to Reduce Delays in Diagnostic Evaluation
      for Cancer: A Cluster Randomized Controlled Trial.
AB  - PURPOSE: We tested whether prospective use of electronic health record-based
      trigger algorithms to identify patients at risk of diagnostic delays could
      prevent delays in diagnostic evaluation for cancer. METHODS: We performed a
      cluster randomized controlled trial of primary care providers (PCPs) at two sites
      to test whether triggers that prospectively identify patients with potential
      delays in diagnostic evaluation for lung, colorectal, or prostate cancer can
      reduce time to follow-up diagnostic evaluation. Intervention steps included
      queries of the electronic health record repository for patients with abnormal
      findings and lack of associated follow-up actions, manual review of triggered
      records, and communication of this information to PCPs via secure e-mail and, if
      needed, phone calls to ensure message receipt. We compared times to diagnostic
      evaluation and proportions of patients followed up between intervention and
      control cohorts based on final review at 7 months. RESULTS: We recruited 72 PCPs
      (36 in the intervention group and 36 in the control group) and applied the
      trigger to all patients under their care from April 20, 2011, to July 19, 2012.
      Of 10,673 patients with abnormal findings, the trigger flagged 1,256 patients
      (11.8%) as high risk for delayed diagnostic evaluation. Times to diagnostic
      evaluation were significantly lower in intervention patients compared with
      control patients flagged by the colorectal trigger (median, 104 v 200 days,
      respectively; n = 557; P < .001) and prostate trigger (40% received evaluation at
      144 v 192 days, respectively; n = 157; P < .001) but not the lung trigger
      (median, 65 v 93 days, respectively; n = 19; P = .59). More intervention patients
      than control patients received diagnostic evaluation by final review (73.4% v
      52.2%, respectively; relative risk, 1.41; 95% CI, 1.25 to 1.58). CONCLUSION:
      Electronic trigger-based interventions seem to be effective in reducing time to
      diagnostic evaluation of colorectal and prostate cancer as well as improving the
      proportion of patients who receive follow-up. Similar interventions could improve
      timeliness of diagnosis of other serious conditions.

PMID- 26304874
TI  - Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration.
AB  - PURPOSE: To review the impact of collaborative studies on advances in the biology
      and treatment of acute lymphoblastic leukemia (ALL) in children and adolescents.
      METHODS: A review of English literature on childhood ALL focusing on
      collaborative studies was performed. The resulting article was reviewed and
      revised by the committee chairs of the major ALL study groups. RESULTS: With long
      term survival rates for ALL approaching 90% and the advent of high-resolution
      genome-wide analyses, several international study groups or consortia were
      established to conduct collaborative research to further improve outcome. As a
      result, treatment strategies have been improved for several subtypes of ALL, such
      as infant, MLL-rearranged, Philadelphia chromosome-positive, and Philadelphia
      chromosome-like ALL. Many recurrent genetic abnormalities that respond to
      tyrosine kinase inhibitors and multiple genetic determinants of drug resistance
      and toxicities have been identified to help develop targeted therapy. Several
      genetic polymorphisms have been recognized that show susceptibility to developing
      ALL and that help explain the racial/ethnic differences in the incidence of ALL.
      CONCLUSION: The information gained from collaborative studies has helped decipher
      the heterogeneity of ALL to help improve personalized treatment, which will
      further advance the current high cure rate and the quality of life for children
      and adolescents with ALL.

PMID- 26304877
TI  - Osteosarcoma: Current Treatment and a Collaborative Pathway to Success.
AB  - Osteosarcoma is the bone tumor that most commonly affects children, adolescents,
      and young adults. Before 1970, treatment primarily included surgical resection.
      However, the introduction of chemotherapy led to a dramatic improvement in
      prognosis for patients with localized osteosarcoma; long-term survival rates of
      less than 20% improved to 65% to 70% after the advent of multiagent chemotherapy
      regimens. Controversy concerning the ideal combination of chemotherapy agents
      ensued throughout the last quarter of the 20th century because of conflicting and
      often nonrandomized data. However, large cooperative group studies and
      international collaboration have demonstrated that the most effective regimens
      include the combination of high-dose methotrexate, doxorubicin, and cisplatin
      (MAP). The introduction of biologic agents such as muramyl tripeptide and the use
      of additional cytotoxic chemotherapy such as ifosfamide have not definitively
      improved the survival of patients with osteosarcoma. Collaborative efforts to
      increase understanding of the biology of osteosarcoma and the use of preclinical
      models to test novel agents will be critical to identify the path toward
      improving outcomes for patients. Once promising agents are identified, an
      international infrastructure exists for clinical trials. Herein, biologic,
      preclinical, and clinical trial efforts will be described along with future
      international collaborative strategies to improve outcomes for patients who
      develop this challenging tumor. 

PMID- 26304879
TI  - Reply to G.D. Aletti et al.

PMID- 26304878
TI  - Association Between Geographic Access to Cancer Care, Insurance, and Receipt of
      Chemotherapy: Geographic Distribution of Oncologists and Travel Distance.
AB  - PURPOSE: Geographic access to care may be associated with receipt of chemotherapy
      but has not been fully examined. This study sought to evaluate the association
      between density of oncologists and travel distance and receipt of adjuvant
      chemotherapy for colon cancer within 90 days of colectomy. PATIENTS AND METHODS:
      Patients in the National Cancer Data Base with stage III colon cancer, diagnosed
      between 2007 and 2010, and age 18 to 80 years were selected. Generalized
      estimating equation clustering by hospital service area was conducted to examine
      the association between geographic access and receipt of oncology services,
      controlling for patient sociodemographic and clinical characteristics. RESULTS:
      Of 34,694 patients in the study cohort, 75.7% received adjuvant chemotherapy
      within 90 days of colectomy. Compared with travel distance less than 12.5 miles,
      patients who traveled 50 to 249 miles (odds ratio [OR], 0.87; P=.009) or >=250
      miles (OR, 0.36; P<.001) had decreased likelihood of receiving adjuvant
      chemotherapy. Density level of oncologists was not statistically associated with
      receipt of adjuvant chemotherapy (low v high density: OR, 0.98; P=.77). When
      stratifying analyses by insurance status, non-privately insured patients who
      resided in areas with low density of oncologists were less likely to receive
      adjuvant chemotherapy (OR, 0.85; P=.03). CONCLUSION: Increased travel burden was
      associated with a decreased likelihood of receiving adjuvant chemotherapy,
      regardless of insurance status. Patients with nonprivate insurance who resided in
      low-density oncologist areas were less likely to receive adjuvant chemotherapy.
      If these findings are validated prospectively, interventions to decrease
      geographic barriers may improve the timeliness and quality of colon cancer
      treatment.

PMID- 26304880
TI  - Bevacizumab Plus Chemotherapy Cost Effectiveness.

PMID- 26304881
TI  - Toward the Cure of All Children With Cancer Through Collaborative Efforts:
      Pediatric Oncology As a Global Challenge.
AB  - Advances in the treatment of childhood cancers have resulted in part from the
      development of national and international collaborative initiatives that have
      defined biologic determinants and generated risk-adapted therapies that maximize
      cure while minimizing acute and long-term effects. Currently, more than 80% of
      children with cancer who are treated with modern multidisciplinary treatments in
      developed countries are cured; however, of the approximately 160,000 children and
      adolescents who are diagnosed with cancer every year worldwide, 80% live in low-
      and middle-income countries (LMICs), where access to quality care is limited and
      chances of cure are low. In addition, the disease burden is not fully known
      because of the lack of population-based cancer registries in low-resource
      countries. Regional and ethnic variations in the incidence of the different
      childhood cancers suggest unique interactions between genetic and environmental
      factors that could provide opportunities for etiologic research. Regional
      collaborative initiatives have been developed in Central and South America and
      the Caribbean, Africa, the Middle East, Asia, and Oceania. These initiatives
      integrate regional capacity building, education of health care providers,
      implementation of intensity-graduated treatments, and establishment of research
      programs that are adjusted to local capacity and local needs. Together, the
      existing consortia and regional networks operating in LMICs have the potential to
      reach out to almost 60% of all children with cancer worldwide. In summary,
      childhood cancer burden has been shifted toward LMICs and, for that reason,
      global initiatives directed at pediatric cancer care and control are needed.
      Regional networks aiming to build capacity while incorporating research on
      epidemiology, health services, and outcomes should be supported. 

PMID- 26304883
TI  - There Is Nothing New Under the Sun.

PMID- 26304882
TI  - Advances in Wilms Tumor Treatment and Biology: Progress Through International
      Collaboration.
AB  - Clinical trials in Wilms tumor (WT) have resulted in overall survival rates of
      greater than 90%. This achievement is especially remarkable because improvements
      in disease-specific survival have occurred concurrently with a reduction of
      therapy for large patient subgroups. However, the outcomes for certain patient
      subgroups, including those with unfavorable histologic and molecular features,
      bilateral disease, and recurrent disease, remain well below the benchmark
      survival rate of 90%. Therapy for WT has been advanced in part by an increasingly
      complex risk-stratification system based on patient age; tumor stage, histology,
      and volume; response to chemotherapy; and loss of heterozygosity at chromosomes
      1p and 16q. A consequence of this system has been the apportionment of patients
      into such small subgroups that only collaboration between large international WT
      study groups will support clinical trials that are sufficiently powered to answer
      challenging questions that move the field forward. This article gives an overview
      of the Children's Oncology Group and International Society of Pediatric Oncology
      approaches to WT and focuses on four subgroups (stage IV, initially inoperable,
      bilateral, and relapsed WT) for which international collaboration is pressing. In
      addition, biologic insights resulting from collaborative laboratory research are
      discussed. A coordinated expansion of international collaboration in both
      clinical trials and laboratory science will provide real opportunity to improve
      the treatment and outcomes for children with renal tumors on a global level. 

PMID- 26304885
TI  - Epidemiology and Clinical Significance of Secondary and Therapy-Related Acute
      Myeloid Leukemia: A National Population-Based Cohort Study.
AB  - PURPOSE: Secondary and therapy-related acute myeloid leukemia (sAML and tAML,
      respectively) remain therapeutic challenges. Still, it is unclear whether their
      inferior outcome compared with de novo acute myeloid leukemia (AML) varies as a
      result of previous hematologic disease or can be explained by differences in
      karyotype and/or age. PATIENTS AND METHODS: In a Danish national population-based
      study of 3,055 unselected patients with AML diagnosed from 2000 to 2013, we
      compared the frequencies and characteristics of tAML, myelodysplastic syndrome
      (MDS) -sAML, and non-MDS-sAML (chronic myelomonocytic leukemia and
      myeloproliferative neoplasia) versus de novo AML. Limited to intensive therapy
      patients, we compared chance of complete remission by logistic regression
      analysis and used a pseudo-value approach to compare relative risk (RR) of death
      at 90 days, 1 year, and 3 years, overall and stratified by age and karyotype.
      Results were given crude and adjusted with 95% CIs. RESULTS: Overall, frequencies
      of sAML and tAML were 19.8% and 6.6%, respectively. sAML, but not tAML, was
      associated with low likelihood of receiving intensive treatment. Among intensive
      therapy patients (n = 1,567), antecedent myeloid disorder or prior cytotoxic
      exposure was associated with decreased complete remission rates and inferior
      survival (3-year adjusted RR for MDS-sAML, non-MDS-sAML, and tAML: RR, 1.14; 95%
      CI, 1.02 to 1.32; RR, 1.27; 95% CI, 1.16 to 1.34; and RR, 1.16; 95% CI, 1.03 to
      1.32, respectively) compared with de novo AML. Among patients >= 60 years old and
      patients with adverse karyotype, previous MDS or tAML did not impact overall
      outcomes, whereas non-MDS-sAML was associated with inferior survival across age
      and cytogenetic risk groups (adverse risk cytogenetics: 1-year adjusted RR, 1.47;
      95% CI, 1.23 to 1.76; patients >= 60 years old: 1-year adjusted RR, 1.31; 95% CI,
      1.06 to 1.61). CONCLUSION: Our results support that de novo AML, sAML, and tAML
      are biologically and prognostically distinct subtypes of AML. Patients with non
      MDS-sAML have dismal outcomes, independent of age and cytogenetics. Previous
      myeloid disorder, age, and cytogenetics are crucial determinants of outcomes and
      should be integrated in treatment recommendations for these patients.

PMID- 26304884
TI  - Pediatric Brain Tumors: Innovative Genomic Information Is Transforming the
      Diagnostic and Clinical Landscape.
AB  - Pediatric neuro-oncology has undergone an exciting and dramatic transformation
      during the past 5 years. This article summarizes data from collaborative group
      and institutional trials that have advanced the science of pediatric brain tumors
      and survival of patients with these tumors. Advanced genomic analysis of the
      entire spectrum of pediatric brain tumors has heralded an era in which
      stakeholders in the pediatric neuro-oncology community are being challenged to
      reconsider their current research and diagnostic and treatment strategies. The
      incorporation of this new information into the next-generation treatment
      protocols will unleash new challenges. This review succinctly summarizes the key
      advances in our understanding of the common pediatric brain tumors (ie,
      medulloblastoma, low- and high-grade gliomas, diffuse intrinsic pontine glioma,
      and ependymoma) and some selected rare tumors (ie, atypical teratoid/rhabdoid
      tumor and CNS primitive neuroectodermal tumor). The potential impact of this new
      information on future clinical protocols also is discussed. Cutting-edge genomics
      technologies and the information gained from such studies are facilitating the
      identification of molecularly defined subgroups within patients with particular
      pediatric brain tumors. The number of evaluable patients in each subgroup is
      small, particularly in the subgroups of rare diseases. Therefore, international
      collaboration will be crucial to draw meaningful conclusions about novel
      approaches to treating pediatric brain tumors. 

PMID- 26304887
TI  - Screening for Lung Cancer: What Comes Next?

PMID- 26304886
TI  - Randomized Trial of Lenalidomide Alone Versus Lenalidomide Plus Rituximab in
      Patients With Recurrent Follicular Lymphoma: CALGB 50401 (Alliance).
AB  - PURPOSE: Lenalidomide and rituximab (LR) are active agents in follicular lymphoma
      (FL). Combination regimens have not been previously assessed in randomized
      studies. PATIENTS AND METHODS: The Cancer and Leukemia Group B (Alliance) 50401
      trial is a randomized phase II trial studying rituximab (375 mg/m(2) weekly for 4
      weeks), lenalidomide (15 mg per day on days 1 to 21, followed by 7 days of rest,
      in cycle 1 and then 20 mg per day on days 1 to 21, followed by 7 days of rest, in
      cycles 2 to 12), or LR. The rituximab-alone arm was discontinued as a result of
      poor accrual. Eligibility included recurrent FL and prior rituximab with time to
      progression of >= 6 months from last dose. Aspirin or heparin was recommended for
      patients at high thrombosis risk. RESULTS: Ninety-one patients (lenalidomide, n =
      45; LR, n = 46) received treatment; median age was 63 years (range, 34 to 89
      years), and 58% were intermediate or high risk according to the Follicular
      Lymphoma International Prognostic Index. In the lenalidomide and LR arms, grade 3
      to 4 adverse events occurred in 58% and 53% of patients, with 9% and 11% of
      patients experiencing grade 4 toxicity, respectively; grade 3 to 4 adverse events
      included neutropenia (16% v 20%, respectively), fatigue (9% v 13%, respectively),
      and thrombosis (16% [n = 7] v 4% [n = 2], respectively; P = .157). Thirty-six
      percent of lenalidomide patients and 63% of LR patients completed 12 cycles.
      Lenalidomide alone was associated with more treatment failures, with 22% of
      patients discontinuing treatment as a result of adverse events. Dose-intensity
      exceeded 80% in both arms. Overall response rate was 53% (20% complete response)
      and 76% (39% complete response) for lenalidomide alone and LR, respectively (P =
      .029). At the median follow-up of 2.5 years, median time to progression was 1.1
      year for lenalidomide alone and 2 years for LR (P = .0023). CONCLUSION: LR is
      more active than lenalidomide alone in recurrent FL with similar toxicity,
      warranting further study in B-cell non-Hodgkin lymphoma as a platform for
      addition of novel agents.

PMID- 26304889
TI  - Fallacy of Quantifying Lymphoma Activity by Scaling to the Liver in
      [18F]Fluorodeoxyglucose Positron Emission Tomography (Deauville criteria).

PMID- 26304888
TI  - Equivalence Ratio for Daunorubicin to Doxorubicin in Relation to Late Heart
      Failure in Survivors of Childhood Cancer.
AB  - PURPOSE: Cumulative anthracycline dose is one of the strongest predictors of
      heart failure (HF) after cancer treatment. However, the differential risk for
      cardiotoxicity between daunorubicin and doxorubicin has not been rigorously
      evaluated among survivors of childhood cancer. These risks, which are based on
      hematologic toxicity, are currently assumed to be approximately equivalent.
      PATIENTS AND METHODS: Data from 15,815 survivors of childhood cancer who survived
      at least 5 years were used. Survivors were from the Emma Children's
      Hospital/Academic Medical Center (n = 1,349), the National Wilms Tumor Study (n =
      364), the St Jude Lifetime Cohort Study (n = 1,695), and the Childhood Cancer
      Survivor Study (n = 12,407). The hazard ratio (HR) for clinical HF through age 40
      years for doses of daunorubicin and doxorubicin (per 100-mg/m(2) increments) was
      estimated by using Cox regression adjusted for sex, age at diagnosis, treatment
      with other anthracycline agents and chest radiation, and cohort membership.
      RESULTS: In total, 5,144 (32.5%) patients received doxorubicin as part of their
      cancer treatment, whereas 2,243 (14.7%) received daunorubicin. On the basis of
      271 occurrences of HF during a median follow-up time after cohort entry of 17.3
      years (range, 0.0 to 35.0 years), the cumulative incidence of HF at age 40 years
      was 3.2% (95% CI, 2.8% to 3.7%). The average ratio of HRs for daunorubicin to
      doxorubicin was 0.45 (95% CI, 0.23 to 0.73). A similar ratio was obtained by
      using a linear dose-response model, which yielded an HR of 0.49 (95% CI, 0.28 to
      0.70). CONCLUSION: Compared with doxorubicin, daunorubicin was less cardiotoxic
      among survivors of childhood cancer than most current guidelines suggest. This
      may have implications for follow-up guidelines. The feasibility of substitution
      of doxorubicin with daunorubicin in childhood cancer treatment protocols to
      reduce cardiotoxicity should be additionally investigated.

PMID- 26304890
TI  - Reply to G. Keramida et al.

PMID- 26304892
TI  - Pediatric Hodgkin Lymphoma.
AB  - Hodgkin lymphoma (HL) is one of the most curable pediatric and adult cancers,
      with long-term survival rates now exceeding 90% after treatment with chemotherapy
      alone or combined with radiotherapy (RT). Of note, global collaboration in
      clinical trials within cooperative pediatric HL study groups has resulted in
      continued progress; however, survivors of pediatric HL are at high risk of
      potentially life-limiting second cancers and treatment-associated cardiovascular
      disease. Over the last three decades, all major pediatric and several adult HL
      study groups have followed the paradigm of response-based treatment adaptation
      and toxicity sparing through the reduction or elimination of RT and tailoring of
      chemotherapy. High treatment efficacy is achieved using dose-dense chemotherapy.
      Refinement and reduction of RT have been implemented on the basis of results from
      collaborative group studies, such that radiation has been completely eliminated
      for certain subgroups of patients. Because pediatric staging and response
      criteria are not uniform, comparing the results of trial series among different
      pediatric and adult study groups remains difficult; thus, initiatives to
      harmonize criteria are desperately needed. A dynamic harmonization process is of
      utmost importance to standardize therapeutic risk stratification and response
      definitions as well as improve the care of children with HL in resource
      restricted environments. 

PMID- 26304891
TI  - Collaborative Research in Childhood Cancer Survivorship: The Current Landscape.
AB  - Survivors of childhood cancer carry a substantial burden of morbidity and are at
      increased risk for premature death. Furthermore, clear associations exist between
      specific therapeutic exposures and the risk for a variety of long-term
      complications. The entire landscape of health issues encountered for decades
      after successful completion of treatment is currently being explored in various
      collaborative research settings. These settings include large population-based or
      multi-institutional cohorts and single-institution studies. The ascertainment of
      outcomes has depended on self-reporting, linkage to registries, or clinical
      assessments. Survivorship research in the cooperative group setting, such as the
      Children's Oncology Group, has leveraged the clinical trials infrastructure to
      explore the molecular underpinnings of treatment-related adverse events, and to
      understand specific complications in the setting of randomized risk-reduction
      strategies. This review highlights the salient findings from these large
      collaborative initiatives, emphasizing the need for life-long follow-up of
      survivors of childhood cancer, and describing the development of several
      guidelines and efforts toward harmonization. Finally, the review reinforces the
      need to identify populations at highest risk, facilitating the development of
      risk prediction models that would allow for targeted interventions across the
      entire trajectory of survivorship. 

PMID- 26304893
TI  - Ewing Sarcoma: Current Management and Future Approaches Through Collaboration.
AB  - Ewing sarcoma (ES) is an aggressive sarcoma of bone and soft tissue occurring at
      any age with a peak incidence in adolescents and young adults. The treatment of
      ES relies on a multidisciplinary approach, coupling risk-adapted intensive
      neoadjuvant and adjuvant chemotherapies with surgery and/or radiotherapy for
      control of the primary site and possible metastatic disease. The optimization of
      ES multimodality therapeutic strategies has resulted from the efforts of several
      national and international groups in Europe and North America and from
      cooperation between pediatric and medical oncologists. Successive first-line
      trials addressed the efficacy of various cyclic combinations of drugs
      incorporating doxorubicin, vincristine, cyclophosphamide, ifosfamide, etoposide,
      and dactinomycin and identified prognostic factors now used to tailor therapies.
      The role of high-dose chemotherapy is still debated. Current 5-year overall
      survival for patients with localized disease is 65% to 75%. Patients with
      metastases have a 5-year overall survival < 30%, except for those with isolated
      pulmonary metastasis (approximately 50%). Patients with recurrence have a dismal
      prognosis. The many insights into the biology of the EWS-FLI1 protein in the
      initiation and progression of ES remain to be translated into novel therapeutic
      strategies. Current options and future approaches will be discussed. 

PMID- 26304894
TI  - Reply to A. Messori et al, R. Bordonaro et al, and G. Fasola et al.

PMID- 26304896
TI  - Selection of Patients for Anti-Epidermal Growth Factor Receptor Treatment in
      Colorectal Cancer: The Potential Pitfalls of Retrospective Analyses of RAS
      Mutations.

PMID- 26304897
TI  - Effectiveness and Cost Effectiveness of Bevacizumab in Metastatic Colorectal
      Cancer.

PMID- 26304895
TI  - Collaborative Efforts Driving Progress in Pediatric Acute Myeloid Leukemia.
AB  - Diagnosis, treatment, response monitoring, and outcome of pediatric acute myeloid
      leukemia (AML) have made enormous progress during the past decades. Because AML
      is a rare type of childhood cancer, with an incidence of approximately seven
      occurrences per 1 million children annually, national and international
      collaborative efforts have evolved. This overview describes these efforts and
      includes a summary of the history and contributions of each of the main
      collaborative pediatric AML groups worldwide. The focus is on translational and
      clinical research, which includes past, current, and future clinical trials.
      Separate sections concern acute promyelocytic leukemia, myeloid leukemia of Down
      syndrome, and relapsed AML. A plethora of novel antileukemic agents that have
      emerged, including new classes of drugs, are summarized as well. Finally, an
      important aspect of the treatment of pediatric AML--supportive care--and late
      effects are discussed. The future is bright, with a wide range of emerging
      innovative therapies and with more and more international collaboration that
      ultimately aim to cure all children with AML, with fewer adverse effects and
      without late effects.

PMID- 26304898
TI  - From Protocols to Publications: A Study in Selective Reporting of Outcomes in
      Randomized Trials in Oncology.
AB  - PURPOSE: The decision by journals to append protocols to published reports of
      randomized trials was a landmark event in clinical trial reporting. However,
      limited information is available on how this initiative effected transparency and
      selective reporting of clinical trial data. METHODS: We analyzed 74 oncology
      based randomized trials published in Journal of Clinical Oncology, the New
      England Journal of Medicine, and The Lancet in 2012. To ascertain integrity of
      reporting, we compared published reports with their respective appended protocols
      with regard to primary end points, nonprimary end points, unplanned end points,
      and unplanned analyses. RESULTS: A total of 86 primary end points were reported
      in 74 randomized trials; nine trials had greater than one primary end point. Nine
      trials (12.2%) had some discrepancy between their planned and published primary
      end points. A total of 579 nonprimary end points (median, seven per trial) were
      planned, of which 373 (64.4%; median, five per trial) were reported. A
      significant positive correlation was found between the number of planned and
      nonreported nonprimary end points (Spearman r = 0.66; P < .001). Twenty-eight
      studies (37.8%) reported a total of 65 unplanned end points; 52 (80.0%) of which
      were not identified as unplanned. Thirty-one (41.9%) and 19 (25.7%) of 74 trials
      reported a total of 52 unplanned analyses involving primary end points and 33
      unplanned analyses involving nonprimary end points, respectively. Studies
      reported positive unplanned end points and unplanned analyses more frequently
      than negative outcomes in abstracts (unplanned end points odds ratio, 6.8; P =
      .002; unplanned analyses odd ratio, 8.4; P = .007). CONCLUSION: Despite public
      and reviewer access to protocols, selective outcome reporting persists and is a
      major concern in the reporting of randomized clinical trials. To foster credible
      evidence-based medicine, additional initiatives are needed to minimize selective
      reporting.

PMID- 26304899
TI  - Balancing Clinical Progress With Economic Sustainability: In Quest of a
      Courageous Solution.

PMID- 26304900
TI  - Impact of an Automatically Generated Cancer Survivorship Care Plan on Patient
      Reported Outcomes in Routine Clinical Practice: Longitudinal Outcomes of a
      Pragmatic, Cluster Randomized Trial.
AB  - PURPOSE: This study was conducted to longitudinally assess the impact of an
      automatically generated survivorship care plan (SCP) on patient-reported outcomes
      in routine clinical practice. Primary outcomes were patient satisfaction with
      information and care. Secondary outcomes included illness perceptions and health
      care use. METHODS: Twelve hospitals were randomly assigned to SCP care or usual
      care in a pragmatic, cluster randomized trial. Newly diagnosed patients with
      endometrial cancer completed questionnaires after diagnosis (n = 221; 75%
      response), 6 months (n = 158), and 12 months (n = 147). An SCP application was
      built in the Web-based ROGY (Registration System Oncological Gynecology). By
      clicking the SCP button, a patient-tailored SCP was generated. RESULTS: In the
      SCP care arm, 74% of patients received an SCP. They reported receiving more
      information about their treatment (mean [M] = 57, standard deviation [SD] = 20 v
      M = 47, SD = 24; P = .03), other services (M = 35, SD = 22 v M = 25, SD = 22; P =
      .03), and different places of care (M = 27, SD = 25 v M = 23, SD = 26; P = .04)
      than the usual care arm (scales, 0 to 100). However, there were no differences
      regarding satisfaction with information or care. Patients in the SCP care arm
      experienced more symptoms (M = 3.3, SD = 2.0 v M = 2.6, SD = 1.6; P = .03), were
      more concerned about their illness (M = 4.4, SD = 2.3 v M = 3.9, SD = 2.1; P =
      .03), were more affected emotionally (M = 4.0, SD = 2.2 v M = 3.7, SD = 2.2; P =
      .046), and reported more cancer-related contact with their primary care physician
      (M = 1.8, SD = 2.0 v M = 1.1, SD = 0.9; P = .003) than those in the usual care
      arm (scale, 1 to 10). These effects did not differ over time. CONCLUSION: The
      present trial showed no evidence of a benefit of SCPs on satisfaction with
      information and care. Furthermore, SCPs increased patients' concerns, emotional
      impact, experienced symptoms, and the amount of cancer-related contact with the
      primary care physician. Whether this may ultimately lead to more empowered
      patients should be investigated further.

PMID- 26304901
TI  - Advances in Risk Classification and Treatment Strategies for Neuroblastoma.
AB  - Risk-based treatment approaches for neuroblastoma have been ongoing for decades.
      However, the criteria used to define risk in various institutional and
      cooperative groups were disparate, limiting the ability to compare clinical trial
      results. To mitigate this problem and enhance collaborative research, homogenous
      pretreatment patient cohorts have been defined by the International Neuroblastoma
      Risk Group classification system. During the past 30 years, increasingly
      intensive, multimodality approaches have been developed to treat patients who are
      classified as high risk, whereas patients with low- or intermediate-risk
      neuroblastoma have received reduced therapy. This treatment approach has resulted
      in improved outcome, although survival for high-risk patients remains poor,
      emphasizing the need for more effective treatments. Increased knowledge regarding
      the biology and genetic basis of neuroblastoma has led to the discovery of
      druggable targets and promising, new therapeutic approaches. Collaborative
      efforts of institutions and international cooperative groups have led to advances
      in our understanding of neuroblastoma biology, refinements in risk
      classification, and stratified treatment strategies, resulting in improved
      outcome. International collaboration will be even more critical when evaluating
      therapies designed to treat small cohorts of patients with rare actionable
      mutations. 

PMID- 26304903
TI  - Cardiovascular Mortality in Testicular Nonseminomatous Germ Cell Tumors: Does
      Statistical Significance Imply Clinical Significance?

PMID- 26304902
TI  - Pediatric and Adolescent Extracranial Germ Cell Tumors: The Road to
      Collaboration.
AB  - During the past 35 years, survival rates for children with extracranial malignant
      germ cell tumors (GCTs) have increased significantly. Success has been achieved
      primarily through the application of platinum-based chemotherapy regimens;
      however, clinical challenges in GCTs remain. Excellent outcomes are not
      distributed uniformly across the heterogeneous distribution of age, histologic
      features, and primary tumor site. Despite good outcomes overall, the likelihood
      of a cure for certain sites and histologic conditions is less than 50%. In
      addition, there are considerable long-term treatment-related effects for
      survivors. Even modest cisplatin dosing can cause significant long-term
      morbidities. A particular challenge in designing new therapies for GCT is that a
      variety of specialists use different risk stratifications, staging systems, and
      treatment approaches for three distinct age groups (childhood, adolescence, and
      young adulthood). Traditionally, pediatric cancer patients younger than 15 years
      have been treated by pediatric oncologists in collaboration with their surgical
      specialty colleagues. Adolescents and young adults with GCTs often are treated by
      medical oncologists, urologists, or gynecologic oncologists. The therapeutic
      dilemma for all is how to best define disease risk so that therapy and toxicity
      can be appropriately reduced for some patients and intensified for others.
      Further clinical and biologic insights can only be achieved through
      collaborations that do not set limitations by age, sex, and primary tumor site.
      Therefore, international collaborations, spanning different cooperative groups
      and disciplines, have been developed to address these challenges. 

PMID- 26304906
TI  - Avoiding Implementation Errors in Cancer Survivorship Care Plan Effectiveness
      Studies.

PMID- 26304904
TI  - Cost-Effectiveness Analysis of Regorafenib for Metastatic Colorectal Cancer.
AB  - PURPOSE: Regorafenib is a standard-care option for treatment-refractory
      metastatic colorectal cancer that increases median overall survival by 6 weeks
      compared with placebo. Given this small incremental clinical benefit, we
      evaluated the cost-effectiveness of regorafenib in the third-line setting for
      patients with metastatic colorectal cancer from the US payer perspective.
      METHODS: We developed a Markov model to compare the cost and effectiveness of
      regorafenib with those of placebo in the third-line treatment of metastatic
      colorectal cancer. Health outcomes were measured in life-years and quality
      adjusted life-years (QALYs). Drug costs were based on Medicare reimbursement
      rates in 2014. Model robustness was addressed in univariable and probabilistic
      sensitivity analyses. RESULTS: Regorafenib provided an additional 0.04 QALYs
      (0.13 life-years) at a cost of $40,000, resulting in an incremental cost
      effectiveness ratio of $900,000 per QALY. The incremental cost-effectiveness
      ratio for regorafenib was > $550,000 per QALY in all of our univariable and
      probabilistic sensitivity analyses. CONCLUSION: Regorafenib provides minimal
      incremental benefit at high incremental cost per QALY in the third-line
      management of metastatic colorectal cancer. The cost-effectiveness of regorafenib
      could be improved by the use of value-based pricing.

PMID- 26304907
TI  - Progress Born From a Legacy of Collaboration.

PMID- 26304905
TI  - Electroacupuncture Versus Gabapentin for Hot Flashes Among Breast Cancer
      Survivors: A Randomized Placebo-Controlled Trial.
AB  - PURPOSE: Hot flashes are a common and debilitating symptom among survivors of
      breast cancer. This study aimed at evaluating the effects of electroacupuncture
      (EA) versus gabapentin (GP) for hot flashes among survivors of breast cancer,
      with a specific focus on the placebo and nocebo effects. PATIENTS AND METHODS: We
      conducted a randomized controlled trial involving 120 survivors of breast cancer
      experiencing bothersome hot flashes twice per day or greater. Participants were
      randomly assigned to receive 8 weeks of EA or GP once per day with validated
      placebo controls (sham acupuncture [SA] or placebo pills [PPs]). The primary end
      point was change in the hot flash composite score (HFCS) between SA and PP at
      week 8, with secondary end points including group comparisons and additional
      evaluation at week 24 for durability of treatment effects. RESULTS: By week 8, SA
      produced significantly greater reduction in HFCS than did PP (-2.39; 95% CI, 
      4.60 to -0.17). Among all treatment groups, the mean reduction in HFCS was
      greatest in the EA group, followed by SA, GP, and PP (-7.4 v -5.9 v -5.2 v -3.4;
      P = < .001). The pill groups had more treatment-related adverse events than did
      the acupuncture groups: GP (39.3%), PP (20.0%), EA (16.7%), and SA (3.1%), with P
      = .005. By week 24, HFCS reduction was greatest in the EA group, followed by SA,
      PP, and GP (-8.5 v -6.1 v -4.6 v -2.8; P = .002). CONCLUSION: Acupuncture
      produced larger placebo and smaller nocebo effects than did pills for the
      treatment of hot flashes. EA may be more effective than GP, with fewer adverse
      effects for managing hot flashes among breast cancer survivors; however, these
      preliminary findings need to be confirmed in larger randomized controlled trials
      with long-term follow-up.

PMID- 26304910
TI  - Reply to S. Debska-Szmich et al.

PMID- 26304909
TI  - Rare Tumors in Children: Progress Through Collaboration.
AB  - Rare pediatric tumors account for approximately 10% of all childhood cancers,
      which in themselves are a rare entity. The diverse histologies and clinical
      behaviors of rare pediatric tumors pose challenges to the investigation of their
      biologic and clinical features. National and international cooperative groups
      such as the Rare Tumor Committee of the Children's Oncology Group, Rare Tumors in
      Pediatric Age Project, and European Cooperative Study Group for Pediatric Rare
      Tumors have developed several initiatives to advance knowledge about rare
      pediatric cancers. However, these programs have been only partially effective,
      necessitating the development of alternative mechanisms to study these
      challenging diseases. In this article, we review the current national and
      international collaborative strategies to study rare pediatric cancers and
      alternative methods under exploration to enhance those efforts, such as
      independent registries and disease-specific, National Cancer Institute-sponsored
      clinics. 

PMID- 26304908
TI  - Non-Hodgkin Lymphoma in Children and Adolescents: Progress Through Effective
      Collaboration, Current Knowledge, and Challenges Ahead.
AB  - Non-Hodgkin lymphoma is the fourth most common malignancy in children, has an
      even higher incidence in adolescents, and is primarily represented by only a few
      histologic subtypes. Dramatic progress has been achieved, with survival rates
      exceeding 80%, in large part because of a better understanding of the biology of
      the different subtypes and national and international collaborations. Most
      patients with Burkitt lymphoma and diffuse large B-cell lymphoma are cured with
      short intensive pulse chemotherapy containing cyclophosphamide, cytarabine, and
      high-dose methotrexate. The benefit of the addition of rituximab has not been
      established except in the case of primary mediastinal B-cell lymphoma.
      Lymphoblastic lymphoma is treated with intensive, semi-continuous, longer
      leukemia-derived protocols. Relapses in B-cell and lymphoblastic lymphomas are
      rare and infrequently curable, even with intensive approaches. Event-free
      survival rates of approximately 75% have been achieved in anaplastic large-cell
      lymphomas with various regimens that generally include a short intensive B-like
      regimen. Immunity seems to play an important role in prognosis and needs further
      exploration to determine its therapeutic application. ALK inhibitor therapeutic
      approaches are currently under investigation. For all pediatric lymphomas, the
      intensity of induction/consolidation therapy correlates with acute toxicities,
      but because of low cumulative doses of anthracyclines and alkylating agents,
      minimal or no long-term toxicity is expected. Challenges that remain include
      defining the value of prognostic factors, such as early response on positron
      emission tomography/computed tomography and minimal disseminated and residual
      disease, using new biologic technologies to improve risk stratification, and
      developing innovative therapies, both in the first-line setting and for relapse. 

PMID- 26304911
TI  - A Randomized, Multicenter, Phase II Study of Cetuximab With Docetaxel and
      Cisplatin as Induction Chemotherapy in Unresectable, Locally Advanced Head and
      Neck Cancer.
AB  - BACKGROUND: We investigated the efficacy of cetuximab when added to induction
      chemotherapy followed by concurrent chemoradiotherapy (CCRT) in patients with
      locally advanced head and neck squamous cell carcinoma. METHODS: Patients were
      randomized to receive three cycles of docetaxel and cisplatin (TP regimen) with
      or without cetuximab (TP plus cetuximab [CTP] vs. TP) as induction chemotherapy.
      Patients in the CTP arm received CCRT with cetuximab and cisplatin, whereas
      patients in the TP arm received cisplatin alone. The primary endpoint was the
      objective response rate (ORR) after induction chemotherapy. RESULTS: Overall, 92
      patients were enrolled. The ORRs for induction chemotherapy in the CTP and TP
      arms were not different (81% vs. 82%). Adding cetuximab lowered the completion
      rate of induction chemotherapy and CCRT and resulted in more frequent dose
      reductions of the induction chemotherapy, although this did not reach statistical
      significance. In the CTP and TP arms, respectively, the 3-year progression-free
      survival (PFS) rates were 70% and 56% (p = .359), and the overall survival (OS)
      rates were 88% and 74% (p = .313). When limited to patients who completed
      induction chemotherapy, 3-year PFS rates of 78% and 59% (p = .085) and OS rates
      of 94% and 73% (p = .045) were observed in the CTP and TP arms, respectively.
      CONCLUSION: Adding cetuximab to sequential treatment did not increase the
      treatment efficacy and resulted in greater toxicity. In the intent-to-treat
      population, neither PFS nor OS was improved by the addition of cetuximab to
      sequential treatment; however, a suggestion of improved survival outcomes was
      observed in patients completing cetuximab-containing induction chemotherapy.

PMID- 26304913
TI  - Fibrinogen and alpha1-antitrypsin in COPD exacerbations.
AB  - BACKGROUND: We tested the hypotheses that fibrinogen and alpha1-antitrypsin are
      observationally and genetically associated with exacerbations in COPD. METHODS:
      We studied 13,591 individuals with COPD from the Copenhagen General Population
      Study (2003-2013), of whom 6857 were genotyped for FGB -455 (rs1800790, G>A) and
      FGB -448 (rs4220, G>A) and had plasma fibrinogen measured. Furthermore, 13,405
      individuals were genotyped for the SERPINA1 S-allele (rs17580) and the Z-allele
      (rs28929474) and had measurements of plasma alpha1-antitrypsin. Exacerbations
      were defined as hospital admissions or treatments with systemic corticosteroids.
      We studied observational associations between plasma measurements and
      exacerbations in Cox regression analyses, associations between genotypes and
      exacerbations in logistic regression analyses and associations between
      genetically determined plasma levels and exacerbations in instrumental variable
      analyses. RESULTS: Elevated fibrinogen and alpha1-antitrypsin levels were
      associated with increased risk of exacerbations in COPD, HR=1.14 (1.07 to 1.22,
      p<0.001) and 1.18 (1.11 to 1.25, p<0.001), respectively, per SD increase.
      Presence of the Z-allele was associated with increased odds of exacerbations,
      OR=1.25 (1.05 to 1.48, p=0.01), as was alpha1-antitrypsin level genetically
      lowered by the Z-allele, OR=1.07 (1.02 to 1.13, p=0.004), per SD decrease.
      Fibrinogen elevating genotypes, FGB -455 (AA) and FGB -448 (AA), were not
      associated with exacerbations, OR=0.96 (0.73 to 1.25, p=0.77) and OR=1.01 (0.75
      to 1.33, p=0.90), respectively, and neither was genetically elevated fibrinogen
      level, OR=1.11 (0.76 to 1.63, p=0.58) per SD increase. CONCLUSIONS: Fibrinogen
      and alpha1-antitrypsin were observationally associated with increased risk of
      exacerbations. However, genetically, fibrinogen per se was not associated with
      exacerbations, while lowered alpha1-antitrypsin was associated with increased
      odds of exacerbations.

PMID- 26304912
TI  - Fibrogenesis in Primary Myelofibrosis: Diagnostic, Clinical, and Therapeutic
      Implications.
AB  - Primary myelofibrosis is a stem cell-derived clonal malignancy characterized by
      unchecked proliferation of myeloid cells, resulting in bone marrow fibrosis,
      osteosclerosis, and pathologic angiogenesis. Bone marrow fibrosis (BMF) plays a
      central role in the pathophysiology of the disease. This review describes current
      issues regarding BMF in primary myelofibrosis, including the pathophysiology and
      impact of abnormal deposition of excess collagen and reticulin fibers in bone
      marrow spaces, the modified Bauermeister and the European Consensus grading
      systems of BMF, and the prognostic impact of BMF on the overall outcome of
      patients with primary myelofibrosis. The impact of novel therapeutic strategies,
      including JAK-STAT inhibitors and allogeneic stem cell transplant, on BMF is
      discussed.

PMID- 26304914
TI  - Cavity Forming Pneumonia Due to Staphylococcus aureus Following Dengue Fever.
AB  - While visiting Malaysia, a 22-year-old previously healthy Japanese man developed
      myalgia, headache, and fever, leading to a diagnosis of classical dengue fever.
      After improvement and returning to Japan after a five day hospitalization, he
      developed productive cough several days after defervescing from dengue. Computed
      tomography (CT) thorax scan showed multiple lung cavities. A sputum smear
      revealed leukocytes with phagocytized gram-positive cocci in clusters, and grew
      an isolate Staphylococcus aureus sensitive to semi-synthetic penicillin; he was
      treated successfully with ceftriaxone and cephalexin. This second reported case
      of pneumonia due to S. aureus occurring after dengue fever, was associated both
      with nosocomial exposure and might have been associated with dengue-associated
      immunosuppression. Clinicians should pay systematic attention to bacterial
      pneumonia following dengue fever to establish whether such a connection is
      causally associated. 

PMID- 26304917
TI  - Border Lookout: Enhancing Tuberculosis Control on the United States-Mexico
      Border.
AB  - We evaluated the use of federal public health intervention tools known as the Do
      Not Board and Border Lookout (BL) for detecting and referring infectious or
      potentially infectious land border travelers with tuberculosis (TB) back to
      treatment. We used data about the issuance of BL from April 2007 to September
      2013 to examine demographics and TB laboratory results for persons on the list (N
      = 66) and time on the list before being located and achieving noninfectious
      status. The majority of case-patients were Hispanic and male, with a median age
      of 39 years. Most were citizens of the United States or Mexico, and 30.3% were
      undocumented migrants. One-fifth had multidrug-resistant TB. Nearly two-thirds of
      case-patients were located and treated as a result of being placed on the list.
      However, 25.8% of case-patients, primarily undocumented migrants, remain lost to
      follow-up and remain on the list. For this highly mobile patient population, the
      use of this novel federal travel intervention tool facilitated the detection and
      treatment of infectious TB cases that were lost to follow-up. 

PMID- 26304915
TI  - Mercadeo Virus: A Novel Mosquito-Specific Flavivirus from Panama.
AB  - Viruses in the genus Flavivirus (family Flaviviridae) include many arthropod
      borne viruses of public health and veterinary importance. However, during the
      past two decades an explosion of novel insect-specific flaviviruses (ISFs), some
      closely related to vertebrate pathogens, have been discovered. Although many
      flavivirus pathogens of vertebrates have been isolated from naturally infected
      mosquitoes in Panama, ISFs have not previously been reported from the country.
      This report describes the isolation and characterization of a novel ISF,
      tentatively named Mercadeo virus (MECDV), obtained from Culex spp. mosquitoes
      collected in Panama. Two MECDV isolates were sequenced and cluster
      phylogenetically with cell-fusing agent virus (CFAV) and Nakiwogo virus (NAKV) to
      form a distinct lineage within the insect-specific group of flaviviruses. 

PMID- 26304916
TI  - Association of Chemotactic Chemokine Ligand 5 Polymorphisms with the Risk of
      Developing Severe Enterovirus 71 Infection.
AB  - Respiratory damage is a main manifestation of severe Enterovirus 71 (EV71)
      infection. Polymorphisms of -403G/A (rs2107538), -28C/G (rs2280788), and In1.1T/C
      (rs2280789) in chemotactic chemokine ligand 5 (CCL5) have linked with many
      respiratory diseases. In this study, we explored the possible correlation of CCL5
      polymorphisms with severe EV71 infection. Blood samples were obtained from 87
      children hospitalized for EV71 infection. Fifty-seven healthy children were
      enrolled as asymptomatic controls. Genotype and allele frequencies were analyzed
      by logistic regression analysis. There were statistically significant differences
      in polymorphisms of CCL5 -403G/A and In1.1T/C for dominant model (P = 0.016; P =
      0.027) and additive model (P = 0.010; P = 0.019) between patients with severe
      EV71 infection and asymptomatic controls. With ordinal logistic regression model
      analysis, statistically significant differences were found between polymorphisms
      of CCL5 (-403G/A) (P = 0.034) with the severity of EV71 infection after adjusting
      for age. The frequency of A-C-C haplotype was significantly higher in EV71
      infection patients than controls (P = 0.032). These results suggest that CCL5 
      403G/A and In1.1T/C polymorphisms may contribute to severe EV71 infection and
      individuals with haplotype of A-C-C may exhibit higher risk of developing severe
      EV71 infection. These findings may provide insights into pathogenic and
      protective mechanisms of severe EV71 infection. 

PMID- 26304918
TI  - Surveillance Potential of Non-Native Hawaiian Birds for Detection of West Nile
      Virus.
AB  - West Nile virus (WNV) was first detected in North America in 1999. Alaska and
      Hawaii (HI) remain the only U.S. states in which transmission of WNV has not been
      detected. Dead bird surveillance has played an important role in the detection of
      the virus geographically, as well as temporally. In North America, corvids have
      played a major role in WNV surveillance; however, the only corvid in HI is the
      endangered Hawaiian crow that exists only in captivity, thus precluding the use
      of this species for WNV surveillance in HI. To evaluate the suitability of
      alternate avian species for WNV surveillance, we experimentally challenged seven
      abundant non-native bird species present in HI with WNV and compared mortality,
      viremia, oral shedding of virus, and seroconversion. For detection of WNV in oral
      swabs, we compared viral culture, reverse-transcriptase polymerase chain
      reaction, and the RAMP((r)) test. For detection of antibodies to WNV, we compared
      an indirect and a competitive enzyme-linked immunoassay. We found four species
      (house sparrow, house finch, Japanese white-eye, and Java sparrow) that may be
      useful in dead bird surveillance for WNV; while common myna, zebra dove, and
      spotted dove survived infection and may be useful in serosurveillance. 

PMID- 26304919
TI  - Complex Type 2 Reactions in Three Patients with Hansen's Disease from a Southern
      United States Clinic.
AB  - In non-endemic countries, leprosy, or Hansen's disease (HD), remains rare and is
      often underrecognized. Consequently, the literature is currently lacking in
      clinical descriptions of leprosy complications in the United States. Immune
      mediated inflammatory states known as reactions are common complications of HD.
      Type 1 reactions are typical of borderline cases and occur in 30% of patients and
      present as swelling and inflammation of existing skin lesions, neuritis, and
      nerve dysfunction. Type 2 reactions are systemic events that occur at the
      lepromatous end of the disease spectrum, and typical symptoms include fever,
      arthralgias, neuritis, and classic painful erythematous skin nodules known as
      erythema nodosum leprosum. We report three patients with lepromatous leprosy seen
      at a U.S. HD clinic with complicated type 2 reactions. The differences in
      presentations and clinical courses highlight the complexity of the disease and
      the need for increased awareness of unique manifestations of lepromatous leprosy
      in non-endemic areas. 

PMID- 26304920
TI  - Pinta: Latin America's Forgotten Disease?
AB  - Pinta is a neglected, chronic skin disease that was first described in the
      sixteenth century in Mexico. The World Health Organization lists 15 countries in
      Latin America where pinta was previously endemic. However, the current prevalence
      of pinta is unknown due to the lack of surveillance data. The etiological agent
      of pinta, Treponema carateum, cannot be distinguished morphologically or
      serologically from the not-yet-cultivable Treponema pallidum subspecies that
      cause venereal syphilis, yaws, and bejel. Although genomic sequencing has enabled
      the development of molecular techniques to differentiate the T. pallidum
      subspecies, comparable information is not available for T. carateum. Because of
      the influx of migrants and refugees from Latin America, U.S. physicians should
      consider pinta in the differential diagnosis of skin diseases in children and
      adolescents who come from areas where pinta was previously endemic and have a
      positive reaction in serological tests for syphilis. All stages of pinta are
      treatable with a single intramuscular injection of penicillin. 

PMID- 26304921
TI  - Measuring Implementation Strength for Integrated Community Case Management in
      Malawi: Results from a National Cell Phone Census.
AB  - Program managers, investors, and evaluators need real-time information on how
      program strategies are being scaled up and implemented. Integrated Community Case
      Management (iCCM) of childhood illnesses is a strategy for increasing access to
      diagnosis and treatment of malaria, pneumonia, and diarrhea through community
      based health workers. We collected real-time data on iCCM implementation strength
      through cell phone interviews with community-based health workers in Malawi and
      calculated indicators of implementation strength and utilization at district
      level using consensus definitions from the Ministry of Health (MOH) and iCCM
      partners. All of the iCCM implementation strength indicators varied widely within
      and across districts. Results show that Malawi has made substantial progress in
      the scale-up of iCCM since the 2008 program launch. However, there are wide
      differences in iCCM implementation strength by district. Districts that performed
      well according to the survey measures demonstrate that MOH implementation
      strength targets are achievable with the right combination of supportive
      structures. Using the survey results, specific districts can now be targeted with
      additional support. 

PMID- 26304922
TI  - Immunocompromised Travelers: Demographic Characteristics, Travel Destinations,
      and Pretravel Health Care from the U.S. Global TravEpiNet Consortium.
AB  - An increasing number of immunocompromised individuals are pursuing international
      travel, and a better understanding of their international travel patterns and
      pretravel health care is needed. We evaluated the clinical features, itineraries,
      and pretravel health care of 486 immunocompromised international travelers seen
      at Global TravEpiNet sites from January 2009 to June 2012. We used bivariate
      analyses and logistic regressions using random intercept models to compare
      demographic and travel characteristics, vaccines administered, and medications
      prescribed for immunocompromised travelers versus 30,702 immunocompetent
      travelers. Immunocompromised travelers pursued itineraries that were largely
      similar to those of immunocompetent travelers, with nearly one-third of such
      travelers visiting countries with low human development indices. Biological
      agents, including tumor necrosis factor blockers, were commonly used
      immunosuppressive medications among immunocompromised travelers. A strong
      collaboration between travel-medicine specialists, primary care doctors, and
      specialist physicians is needed to prepare immunocompromised people for
      international travel. Incorporating routine questioning and planning regarding
      travel into the primary care visits of immunocompromised people may be useful. 

PMID- 26304923
TI  - Successful Treatment of Chromobacterium violaceum Sepsis in a South Indian Adult.
AB  - Infection due to Chromobacterium violaceum is rare. Diagnosis may be delayed
      since Chromobacterium sepsis may mimic melioidosis, especially in melioidosis
      endemic areas. Management of Chromobacterium infection is challenging given the
      propensity of this pathogen to cause visceral abscesses, drug resistance, and
      relapse. Mortality rates are high despite treatment. We report a case of C.
      violaceum septicemia in an immunocompetent adult from south India, who was
      successfully treated with combination antibiotic therapy. Physicians in tropical
      and subtropical regions must be aware of C. violaceum infection as it can mimic
      melioidosis. 

PMID- 26304924
TI  - Serum Anti-Cryptosporidial gp15 Antibodies in Mothers and Children Less than 2
      Years of Age in India.
AB  - Little is known about the type and longevity of the humoral response to
      cryptosporidial infections in developing countries. We evaluated serum antibody
      response to Cryptosporidium gp15 in 150 sets of maternal, preweaning and
      postinfection/end-of-follow-up sera from children followed up to 2 years of age
      to determine the influence of maternal and preweaning serological status on
      childhood cryptosporidiosis. Fifty two percent (N = 78) of mothers and 20% (N =
      30) of children were seropositive preweaning. However, most positive preweaning
      samples from children were collected early in life indicating transplacental
      transfer and subsequent rapid waning of antibodies. Although 62% (N = 94) of
      children had a parasitologically confirmed cryptosporidial infection (detected by
      stool polymerase chain reaction) during the follow-up, only 54% (N = 51) of
      children were seropositive postinfection. Given there were striking differences
      in seropositivity depending on when the sample was collected, even though
      Cryptosporidium was detected in the stool of the majority of the children, this
      study indicates that antibodies wane rapidly. During follow-up, the acquisition
      or severity of cryptosporidial infections was not influenced by maternal (P =
      0.331 and 0.720, respectively) as well as the preweaning serological status of
      the child (P = 0.076 and 0.196, respectively). 

PMID- 26304925
TI  - Patterns of Flavivirus Seroprevalence in the Human Population of Northern Laos.
AB  - A total of 1,136 samples from 289 households in four provinces in northern Laos
      were subjected to Japanese encephalitis virus (JEV) and dengue virus
      hemagglutination inhibition (DENV HI). Overall, antibodies to JEV were detected
      by HI in 620 (54.6%) of 1,136 people; of which 217 (19.1%) had HI activity
      against JEV only. Antibodies to DENV4 were detected by HI in 526 (46.3%) of 1,136
      people; of which 124 (10.9%) had HI activity against DENV4 only. Antibodies to
      DENV1-3 were detected by HI in 296 (26.1%), 274 (24.1%), and 283 (24.9) of 1,136
      people, respectively; of which 7, 1, and 0, respectively, had HI activity against
      DENV1-3 only. JEV was the most prevalent Flavivirus in Oudomxay, Luangprabang,
      and Huaphan provinces and DENV4 was the most prevalent in Xiengkhouang province.
      Seroprevalence for JEV increased with increasing age and wealth and was higher in
      villages where rice was cultivated in paddy fields and highest for people of Lao
      Tai ethnicity. 

PMID- 26304926
TI  - Androgen receptor (AR) suppresses miRNA-145 to promote renal cell carcinoma (RCC)
      progression independent of VHL status.
AB  - Mutational inactivation of the VHL tumor suppressor plays key roles in the
      development of renal cell carcinoma (RCC), and mutated VHL-mediated VEGF
      induction has become the main target for the current RCC therapy. Here we
      identified a signal pathway of VEGF induction by androgen receptor (AR)/miRNA-145
      as a new target to suppress RCC progression. Mechanism dissection revealed that
      AR might function through binding to the androgen receptor element (ARE) located
      on the promoter region of miRNA-145 to suppress p53's ability to induce
      expression of miRNA-145 that normally suppresses expression of
      HIF2alpha/VEGF/MMP9/CCND1. Suppressing AR with AR-shRNA or introducing exogenous
      miRNA-145 mimic can attenuate RCC progression independent of VHL status. MiR-145
      mimic in preclinical RCC orthotopic xenograft mouse model revealed its efficacy
      in suppression of RCC progression. These results together identified signals by
      AR-suppressed miRNA-145 as a key player in the RCC progression via regulating
      HIF2alpha/VEGF/MMP9/CCND1 expression levels. Blockade of the newly identified
      signal by AR inhibition or miRNA-145 mimics has promising therapeutic benefit to
      suppress RCC progression.

PMID- 26304927
TI  - Understanding of tolerance in TRAIL-induced apoptosis and cancelation of its
      machinery by alpha-mangostin, a xanthone derivative.
AB  - Tumor necrosis-factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member
      of the TNF-superfamily that selectively induces apoptosis through death receptors
      (DRs) 4 and/or 5 in cancer cells. These receptors are expressed on the cancer
      cell surface, without affecting normal cells. Unfortunately, many clinical
      studies have shown that cancer cells acquire TRAIL-resistance and finally avoid
      TRAIL-induced apoptosis. The detailed mechanisms of this resistance are not well
      understood. In the current study, we established a TRAIL-resistant human colon
      cancer DLD-1 cell line to clarify the mechanisms of TRAIL-resistance and
      developed agents to cancel its machinery. Also, we found that cancer stem-like
      cells from breast epithelial proliferating MCF10A cells were also sensitive to
      TRAIL-induced apoptosis. The enforced expression of DR5 in both TRAIL-resistant
      cells partially recovered the sensitivity to the TRAIL ligand, which was judged
      by the activation of caspase-8. As a result, we newly found that the mechanisms
      of TRAIL-resistance comprised co-existence of a decrease in the expression level
      of DR5 along with malfunction of its recruitment to the cell surface, as
      evidenced by Western blot and immunocytological analysis, respectively.
      Interestingly, alpha-mangostin, which is a xanthone derivative, canceled the
      resistance by increasing the expression level of DR5 through down-regulation of
      miR-133b and effectively induced the translocation of DR5 to the cancer cell
      surface membrane in TRAIL-resistant DLD-1 cells. These findings indicate that
      alpha-mangostin functioned as a sensitizer of TRAIL-induced apoptosis and may
      thus serve as a possible adjuvant compound for cytokine therapy to conquer TRAIL
      resistance. 

PMID- 26304928
TI  - Reproductive factors and hormone receptor status among very young (<35 years)
      breast cancer patients.
AB  - The prognosis for breast cancer occurs in young women is usually poor. The impact
      of different reproductive factors on disease characteristics is still largely
      unknown. We analyzed 261 patients aged <=35 years old who were treated at the
      Cancer Hospital of Fudan University, Shanghai, China. The relationships between
      certain reproductive factors (age at menarche, parity, number of children,
      breastfeeding, history of abortion, age at first full-term pregnancy and oral
      contraceptive (OC) use) and disease characteristics were evaluated. Compared with
      patients who experienced fewer full-term pregnancies (<2 times), the patients
      with more full-term pregnancies (>=2 times) exhibited higher percentage of ER
      positive tumors (61.5%) (P = 0.015), and patients whose age of menarche was >=15
      years exhibited a greater chance of PR-positive tumors (64.8%) (P = 0.036)
      compared with those whose age of menarche was <15 years old. Additionally,
      patients who had taken OCs were more likely to present with late-stage tumors (II
      stage or later) (87.5%) (P = 0.002) than patients who had never taken OCs. Our
      study provides evidence that women with more full-term pregnancies and later age
      at menarche are more possible to exhibit hormone receptor-positive tumors.
      Additionally, patients who have taken OCs are more likely to present with
      advanced disease. 

PMID- 26304930
TI  - The impact of ribavirin plasma concentration on the efficacy of the interferon
      sparing regimen, sofosbuvir and ribavirin.
AB  - BACKGROUND: Ribavirin augments sustained virological response when administered
      with pegylated interferon for the treatment of chronic HCV infection. The impact
      of ribavirin plasma concentration on outcome in individuals receiving interferon
      free regimens has not been evaluated. METHODS: Stored plasma samples were
      retrieved for 47 treatment-naive subjects who received sofosbuvir and weight
      based ribavirin for 12-24 weeks in the Phase IIb QUANTUM study. Week 1, 4 and 8
      ribavirin plasma concentrations (mg/l) were quantified using high-performance
      liquid chromatography with UV detection. RESULTS: Sustained virological response
      at 12 weeks post treatment was observed in 55% with all treatment failures due to
      relapse. The median ribavirin plasma concentration increased from week 1 (1.58
      mg/l, IQR 1.44-2.24) to week 4 (2.23 mg/l, IQR 1.69-2.87) and week 8 (2.67 mg/l,
      IQR 2.10-3.26) with wide variability at steady state. Median week 4 ribavirin
      plasma concentration was 2.25 mg/l (IQR 1.63-3.05) in those with a sustained
      virological response as compared to 2.07 mg/l (IQR 1.79-2.86) in those with
      treatment failure (OR 1.35; 95% CI 0.76, 2.39; P=0.3). No significant association
      between ribavirin plasma concentration and treatment response was noted at weeks
      1 or 8. CONCLUSIONS: We found no evidence of an association between ribavirin
      plasma concentrations and relapse suggesting that, as opposed to interferon-based
      therapy, suboptimal ribavirin plasma concentrations did not explain the high rate
      of virological failure with this regimen. Our findings suggest that in interferon
      free ribavirin-containing regimens, concerns over ribavirin dosing to achieve
      previously determined target plasma concentrations are unnecessary.

PMID- 26304931
TI  - Effects of Formulation Variables on the Particle Size and Drug Encapsulation of
      Imatinib-Loaded Solid Lipid Nanoparticles.
AB  - Imatinib (IMT), an anticancer agent, inhibits receptor tyrosine kinases and is
      characterized by poor aqueous solubility, extensive first-pass metabolism, and
      rapid clearance. The aims of the current study are to prepare imatinib-loaded
      solid lipid nanoparticles (IMT-SLN) and study the effects of associated
      formulation variables on particle size and drug encapsulation on IMT-SLN using an
      experimental design. IMT-SLN was optimized by use of a "combo" approach involving
      Plackett-Burman design (PBD) and Box-Behnken design (BBD). PBD screening resulted
      in the determination of organic-to-aqueous phase ratio (O/A), drug-to-lipid ratio
      (D/L), and amount of Tween(r) 20 (Tw20) as three significant variables for
      particle size (S z), drug loading (DL), and encapsulation efficiency (EE) of IMT
      SLN, which were used for optimization by BBD, yielding an optimized criteria of
      O/A = 0.04, D/L = 0.03, and Tw20 = 2.50% w/v. The optimized IMT-SLN exhibited
      monodispersed particles with a size range of 69.0 +/- 0.9 nm, zeta-potential of 
      24.2 +/- 1.2 mV, and DL and EE of 2.9 +/- 0.1 and 97.6 +/- 0.1% w/w,
      respectively. Results of in vitro release study showed a sustained release
      pattern, presumably by diffusion and erosion, with a higher release rate at pH
      5.0, compared to pH 7.4. In conclusion, use of the combo experimental design
      approach enabled clear understanding of the effects of various formulation
      variables on IMT-SLN and aided in the preparation of a system which exhibited
      desirable physicochemical and release characteristics. 

PMID- 26304929
TI  - Targeting activating mutations of EZH2 leads to potent cell growth inhibition in
      human melanoma by derepression of tumor suppressor genes.
AB  - The epigenetic modifier EZH2 is part of the polycomb repressive complex that
      suppresses gene expression via histone methylation. Activating mutations in EZH2
      are found in a subset of melanoma that contributes to disease progression by
      inactivating tumor suppressor genes. In this study we have targeted EZH2 with a
      specific inhibitor (GSK126) or depleted EZH2 protein by stable shRNA knockdown.
      We show that inhibition of EZH2 has potent effects on the growth of both wild
      type and EZH2 mutant human melanoma in vitro particularly in cell lines harboring
      the EZH2Y646 activating mutation. This was associated with cell cycle arrest,
      reduced proliferative capacity in both 2D and 3D culture systems, and induction
      of apoptosis. The latter was caspase independent and mediated by the release of
      apoptosis inducing factor (AIFM1) from mitochondria. Gene expression arrays
      showed that several well characterized tumor suppressor genes were reactivated by
      EZH2 inhibition. This included activating transcription factor 3 (ATF3) that was
      validated as an EZH2 target gene by ChIP-qPCR. These results emphasize a critical
      role for EZH2 in the proliferation and viability of melanoma and highlight the
      potential for targeted therapy against EZH2 in treatment of patients with
      melanoma. 

PMID- 26304932
TI  - Enhancement of Bioavailability and Pharmacodynamic Effects of Thymoquinone Via
      Nanostructured Lipid Carrier (NLC) Formulation.
AB  - Thymoquinone (TQ), obtained from black cumin (Nigella sativa), is a natural
      product with anti-oxidant, anti-inflammatory, and hepatoprotective effects but
      unfortunately with poor bioavailability. Aiming to improve its poor oral
      bioavailability, TQ-loaded nanostructured lipid carriers (NLCs) were prepared by
      high-speed homogenization followed by ultrasonication and evaluated in vitro.
      Bioavailability and pharmacodynamic studies were also performed. The resultant
      NLCs showed poor physical homogeneity in Compritol 888 ATO Pluronic F127 system
      which consequently produced larger particle size and polydispersity index,
      smaller zeta potential values, and lower short-term (30 days) physical stability
      than other systems. Encapsulation efficiency percentage (EE%) lied between 84.6
      +/- 5% and 96.2 +/- 1.6%. TQ AUC0-t values were higher in animals treated with
      NLCs, with a relative bioavailability of 2.03- and 3.97-fold (for F9 and F12,
      respectively) higher than TQ suspension, indicating bioavailability enhancement
      by NLC formulation. Hepatoprotective effects of F12 showed significant (P < 0.05)
      decrease in both serum alanine amino transferase and aspartate amino transferase
      to reach 305.0 +/- 24.88 and 304.7 +/- 23.55 U/ml, respectively, when compared
      with untreated toxic group. Anti-oxidant efficacy of F12 showed significant (P <
      0.05) decline of malondialdehyde and elevation of reduced glutatione. This
      improvement was also confirmed histopathologically. 

PMID- 26304934
TI  - Infarct Size, Shock, and Heart Failure: Does Reperfusion Strategy Matter in Early
      Presenting Patients With ST-Segment Elevation Myocardial Infarction?
AB  - BACKGROUND: A pharmacoinvasive (PI) strategy for early presenting ST-segment
      elevation myocardial infarction nominally reduced 30-day cardiogenic shock and
      congestive heart failure compared with primary percutaneous coronary intervention
      (PPCI). We evaluated whether infarct size (IS) was related to this finding.
      METHODS AND RESULTS: Using the peak cardiac biomarker in patients randomized to
      PI versus PPCI within the Strategic Reperfusion Early After Myocardial Infarction
      (STREAM) trial, IS was divided into 3 groups: small (<=2 times the upper limit
      normal [ULN]), medium (>2 to <=5 times the upper limit normal) and large (>5
      times the upper limit normal). The association between IS and 30-day shock and
      congestive heart failure was subsequently examined. Data on 1701 of 1892 (89.9%)
      patients randomized to PI (n=853, 50.1%) versus PPCI (n=848, 49.9%) within STREAM
      were evaluated. A higher proportion of PPCI patients had a large IS (PI versus
      PPCI: small, 49.8% versus 50.2%; medium, 56.9% versus 43.1%; large, 48.4% versus
      51.6%; P=0.035), despite comparable intergroup ischemic times for each
      reperfusion strategy. As IS increased, a parallel increment in shock and
      congestive heart failure occurred in both treatment arms, except for the small IS
      group. The difference in shock and congestive heart failure in the small IS group
      (4.4% versus 11.6%, P=0.026) in favor of PI likely relates to higher rates of
      aborted myocardial infarction with the PI strategy (72.7% versus 54.3%, P=0.005).
      After adjustment, a trend favoring PI persisted in this subgroup (relative risk
      0.40, 95% CI 0.15 to 1.06, P=0.064); no difference in treatment-related outcomes
      was evident in the other 2 groups. CONCLUSION: A PI strategy appears to alter the
      pattern of IS after ST-segment elevation myocardial infarction, resulting in more
      medium and fewer large infarcts compared with PPCI. Despite a comparable number
      of small infarcts, PI patients in this group had more aborted myocardial
      infarctions and less 30-day shock and congestive heart failure. CLINICAL TRIAL
      REGISTRATION: URL: http://ClinicalTrials.gov. Unique identifier: NCT00623623.

PMID- 26304935
TI  - Acute Heart Failure and Atrial Fibrillation: Insights From the Acute Study of
      Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF)
      Trial.
AB  - BACKGROUND: Patients with acute heart failure (AHF) frequently have atrial
      fibrillation (AF), but how this affects patient-reported outcomes has not been
      well characterized. METHODS AND RESULTS: We examined dyspnea improvement and
      clinical outcomes in 7007 patients in the Acute Study of Clinical Effectiveness
      of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial. At baseline, 2677
      (38.2%) patients had current or a history of AF and 4330 (61.8%) did not.
      Patients with a history of AF were older than those without (72 vs. 63 years) and
      had more comorbidities and a higher median left ventricular ejection fraction
      (31% vs. 27%, P<0.001). Compared to those without AF, patients with AF had a
      similar mean ventricular rate on admission (81 vs. 83 beats per minute [bpm];
      P=0.138) but a lower rate at discharge (75 vs. 78 bpm; P<0.001). There was no
      difference in dyspnea improvement between patients with and without AF at 6 hours
      (P=0.087), but patients with AF had less dyspnea improvement at 24 hours
      (P<0.001). Compared to patients without AF, patients with AF had a higher 30-day
      all-cause mortality rate (4.7% vs. 3.3%; P=0.005), a higher 30-day HF
      rehospitalisation rate (7.2% vs. 5.3%; P=0.001), and a higher coprimary composite
      outcome of 30-day death or readmission (11.6% vs. 8.6%; P<0.001). This difference
      persisted after adjustment for prognostic variables (adjusted odds ratio=1.19;
      (95% confidence interval, 1.02 to 1.38; P=0.029). CONCLUSIONS: Among patients
      admitted to the hospital with AHF, current or a history of AF is associated with
      less dyspnea improvement and higher morbidity and mortality at 30-days, compared
      to those not in AF. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00475852.

PMID- 26304936
TI  - Circulating microRNA Profiling Needs Further Refinement Before Clinical Use in
      Patients With Aortic Stenosis.
AB  - BACKGROUND: Aortic stenosis (AS) is a progressive condition leading to heart
      failure and death without treatment. No medical therapy currently exists for AS,
      and a major management challenge is deciding on the correct timing of aortic
      valve replacement. MicroRNAs (miRNAs) are short noncoding RNAs that are stable in
      the circulation. We wished to use miRNAs as biomarkers of disease in AS. METHODS
      AND RESULTS: We performed microarray-based whole miRNome profiling of 24
      participants with AS and 27 control participants. After adjustment for age and
      multiple testing, we identified 4 miRNAs significantly different between groups.
      These findings were then examined using quantitative polymerase chain reaction in
      a larger validation cohort of 101 controls and 94 participants with AS,
      stratified in a prespecified analysis by presence of coexisting coronary artery
      disease (CAD). We obtained mixed results for miR-22-3p, miR-24-3p, miR-382-5p,
      and miR-451a in the validation cohort, with differing associations according to
      CAD status. miR-21-5p was increased in AS patients without CAD, but there was no
      difference between groups with CAD. CONCLUSION: Despite holding great promise,
      circulating miRNA profiling requires further refinement before translation into
      clinical use as a biomarker in aortic stenosis.

PMID- 26304937
TI  - Long-Term Antiplatelet Mono- and Dual Therapies After Ischemic Stroke or
      Transient Ischemic Attack: Network Meta-Analysis.
AB  - BACKGROUND: The latest guidelines do not make clear recommendations on the
      selection of antiplatelet therapies for long-term secondary prevention of stroke.
      We aimed to integrate the available evidence to create hierarchies of the
      comparative efficacy and safety of long-term antiplatelet therapies after
      ischemic stroke or transient ischemic attack. METHODS AND RESULTS: We performed a
      network meta-analysis of randomized controlled trials to compare 11 antiplatelet
      therapies in patients with ischemic stroke or transient ischemic attack. In
      December 2014, we searched Medline, Embase, and the Cochrane Library database for
      trials. The search identified 24 randomized controlled trials including a total
      of 85 667 patients with antiplatelet treatments for at least 1 year. Cilostazol
      significantly reduced stroke recurrence in comparison with aspirin (odds ratio
      0.66, 95% credible interval 0.44 to 0.92) and dipyridamole (odds ratio 0.57, 95%
      credible interval 0.34 to 0.95), respectively. Cilostazol also significantly
      reduced intracranial hemorrhage compared with aspirin, clopidogrel, terutroban,
      ticlopidine, aspirin plus clopidogrel, and aspirin plus dipyridamole. Aspirin
      plus clopidogrel could not significantly reduce stroke recurrence compared with
      monotherapies but caused significantly more major bleeding than all monotherapies
      except terutroban. The pooled estimates did not change materially in the
      sensitivity analyses of the primary efficacy outcome. CONCLUSIONS: Long-term
      monotherapy was a better choice than long-term dual therapy, and cilostazol had
      the best risk-benefit profile for long-term secondary prevention after stroke or
      transient ischemic attack. More randomized controlled trials in non-East Asian
      patients are needed to determine whether long-term use of cilostazol is the best
      option for the prevention of recurrent stroke.

PMID- 26304938
TI  - Dabigatran is Less Effective Than Warfarin at Attenuating Mechanical Heart Valve
      Induced Thrombin Generation.
AB  - BACKGROUND: Patients with mechanical heart valves (MHV) require warfarin to
      prevent thromboembolism. Although dabigatran was as effective as warfarin for
      stroke prevention in atrial fibrillation when compared with warfarin in patients
      with MHV, the study was stopped early because of more strokes and bleeding with
      dabigatran. To determine why dabigatran was less effective than warfarin, we
      compared their effects on thrombin generation induced by MHV. METHODS AND
      RESULTS: Thrombin generation in the absence or presence of valve leaflets or
      sewing ring segments (SRS) was quantified. Studies were done in control plasma,
      plasma depleted of factors (F) XII, XI, or VII, plasma containing varying
      concentrations of dabigatran, or plasma from patients on dabigatran or warfarin
      with varying dabigatran concentrations or international normalized ratio (INR)
      values. Mean endogenous thrombin potential (ETP) increased 1.2-, 1.5-, and 1.8
      fold in the presence of leaflets, Teflon SRS, and Dacron SRS, respectively.
      Whereas ETP in FVII-depleted and control plasma was similar, ETP was reduced to
      background levels in FXII-depleted plasma and abrogated in FXI-depleted plasma.
      Dabigatran had little effect on ETP at concentrations below 400 ng/mL, whereas in
      plasma from warfarin-treated patients, ETP was suppressed with INR values over
      1.5. CONCLUSIONS: MHV induce thrombin generation via the intrinsic pathway and
      generate sufficient thrombin to overwhelm clinically relevant dabigatran
      concentrations. In contrast, warfarin is more effective than dabigatran at
      suppressing MHV-induced thrombin generation. These data explain why dabigatran
      failed in MHV patients and suggest that strategies targeting FXII or FXI may
      suppress the root cause of thrombosis in such patients.

PMID- 26304939
TI  - Adenosine Triphosphate-Sensitive Potassium Channel Kir Subunits Implicated in
      Cardioprotection by Diazoxide.
AB  - BACKGROUND: ATP-sensitive potassium (K(ATP)) channel openers provide
      cardioprotection in multiple models. Ion flux at an unidentified mitochondrial
      K(ATP) channel has been proposed as the mechanism. The renal outer medullary
      kidney potassium channel subunit, potassium inward rectifying (Kir)1.1, has been
      implicated as a mitochondrial channel pore-forming subunit. We hypothesized that
      subunit Kir1.1 is involved in cardioprotection (maintenance of volume homeostasis
      and contractility) of the K(ATP) channel opener diazoxide (DZX) during stress
      (exposure to hyperkalemic cardioplegia [CPG]) at the myocyte and mitochondrial
      levels. METHODS AND RESULTS: Kir subunit inhibitor Tertiapin Q (TPN-Q) was
      utilized to evaluate response to stress. Mouse ventricular mitochondrial volume
      was measured in the following groups: isolation buffer; 200 MUmol/L of ATP; 100
      MUmol/L of DZX+200 MUmol/L of ATP; or 100 MUmol/L of DZX+200 MUmol/L of ATP+TPN-Q
      (500 or 100 nmol/L). Myocytes were exposed to Tyrode's solution (5 minutes), test
      solution (Tyrode's, cardioplegia [CPG], CPG+DZX, CPG+DZX+TPN-Q, Tyrode's+TPN-Q,
      or CPG+TPN-Q), N=12 for all (10 minutes); followed by Tyrode's (5 minutes).
      Volumes were compared. TPN-Q, with or without DZX, did not alter mitochondrial or
      myocyte volume. Stress (CPG) resulted in myocyte swelling and reduced
      contractility that was prevented by DZX. TPN-Q prevented the cardioprotection
      afforded by DZX (volume homeostasis and maintenance of contractility).
      CONCLUSIONS: TPN-Q inhibited myocyte cardioprotection provided by DZX during
      stress; however, it did not alter mitochondrial volume. Because TPN-Q inhibits
      Kir1.1, Kir3.1, and Kir3.4, these data support that any of these Kir subunits
      could be involved in the cardioprotection afforded by diazoxide. However, these
      data suggest that mitochondrial swelling by diazoxide does not involve Kir1.1,
      3.1, or 3.4.

PMID- 26304940
TI  - Inactivation of Endothelial Small/Intermediate Conductance of Calcium-Activated
      Potassium Channels Contributes to Coronary Arteriolar Dysfunction in Diabetic
      Patients.
AB  - BACKGROUND: Diabetes is associated with coronary arteriolar endothelial
      dysfunction. We investigated the role of the small/intermediate (SK(Ca)/IK(Ca))
      conductance of calcium-activated potassium channels in diabetes-related
      endothelial dysfunction. METHODS AND RESULTS: Coronary arterioles (80 to 150 MUm
      in diameter) were dissected from discarded right atrial tissues of diabetic
      (glycosylated hemoglobin = 9.6+/-0.25) and nondiabetic patients (glycosylated
      hemoglobin 5.4+/-0.12) during coronary artery bypass graft surgery (n=8/group).
      In-vitro relaxation response of precontracted arterioles was examined in the
      presence of the selective SK(Ca)/IK(Ca) activator NS309 and other vasodilatory
      agents. The channel density and membrane potential of diabetic and nondiabetic
      endothelial cells was measured by using the whole cell patch-clamp technique. The
      protein expression and distribution of the SK(Ca)/IK(Ca) in the human myocardium
      and coronary arterioles was examined by Western blotting and
      immunohistochemistry. Our results indicate that diabetes significantly reduced
      the coronary arteriolar response to the SK(Ca)/IK(Ca) activator NS309 compared to
      the respective responses of nondiabetic vessels (P<0.05 versus nondiabetes). The
      relaxation response of diabetic arterioles to NS309 was prevented by denudation
      of endothelium (P=0.001 versus endothelium-intact). Diabetes significantly
      decreased endothelial SK(Ca)/IK(Ca) currents and hyperpolarization induced by the
      SK(Ca)/IK(Ca) activator NS309 as compared with that of nondiabetics. There were
      no significant differences in the expression and distribution of SK(Ca)/IK(Ca)
      proteins in the coronary microvessels. CONCLUSIONS: Diabetes is associated with
      inactivation of endothelial SK(Ca)/IK(Ca) channels, which may contribute to
      endothelial dysfunction in diabetic patients.

PMID- 26304943
TI  - Doctoral Education in Dental Hygiene: From Dream to Reality - Almost!

PMID- 26304942
TI  - Is There a Role for Colchicine in Acute Coronary Syndromes?

PMID- 26304941
TI  - Colchicine Acutely Suppresses Local Cardiac Production of Inflammatory Cytokines
      in Patients With an Acute Coronary Syndrome.
AB  - BACKGROUND: Interleukin (IL)-1beta, IL-18, and downstream IL-6 are key
      inflammatory cytokines in the pathogenesis of coronary artery disease. Colchicine
      is believed to block the NLRP3 inflammasome, a cytosolic complex responsible for
      the production of IL-1beta and IL-18. In vivo effects of colchicine on cardiac
      cytokine release have not been previously studied. This study aimed to (1) assess
      the local cardiac production of inflammatory cytokines in patients with acute
      coronary syndromes (ACS), stable coronary artery disease and in controls; and (2)
      determine whether acute administration of colchicine inhibits their production.
      METHODS AND RESULTS: Forty ACS patients, 33 with stable coronary artery disease,
      and 10 controls, were included. ACS and stable coronary artery disease patients
      were randomized to oral colchicine treatment (1 mg followed by 0.5 mg 1 hour
      later) or no colchicine, 6 to 24 hours prior to cardiac catheterization. Blood
      samples from the coronary sinus, aortic root (arterial), and lower right atrium
      (venous) were collected and tested for IL-1beta, IL-18, and IL-6 using ELISA. In
      ACS patients, coronary sinus levels of IL-1beta, IL-18, and IL-6 were
      significantly higher than arterial and venous levels (P=0.017, <0.001 and <0.001,
      respectively). Transcoronary (coronary sinus-arterial) gradients for IL-1beta, IL
      18, and IL-6 were highest in ACS patients and lowest in controls (P=0.077, 0.033,
      and 0.014, respectively). Colchicine administration significantly reduced
      transcoronary gradients of all 3 cytokines in ACS patients by 40% to 88%
      (P=0.028, 0.032, and 0.032, for IL-1beta, IL-18, and IL-6, respectively).
      CONCLUSIONS: ACS patients exhibit increased local cardiac production of
      inflammatory cytokines. Short-term colchicine administration rapidly and
      significantly reduces levels of these cytokines.

PMID- 26304944
TI  - Lasers and Nonsurgical Periodontal Therapy.
AB  - The purpose of Linking Research to Clinical Practice is to present evidence based
      information to clinical dental hygienists so that they can make informed
      decisions regarding patient treatment and recommendations. Each issue will
      feature a different topic area of importance to clinical dental hygienists with A
      BOTTOM LINE to translate the research findings into clinical application. 

PMID- 26304945
TI  - Perceptions of Dental Hygiene Master's Degree Learners About Dental Hygiene
      Doctoral Education.
AB  - PURPOSE: To determine perceptions about dental hygiene doctoral education among
      dental hygiene master's degree program enrollees. METHODS: In this cross
      sectional national study, all dental hygiene master degree program directors were
      sent an email requesting they forward an attached consent form and online-survey
      link to their graduate learners. The 29-item online survey assessed their
      perceptions about need for, importance of and interest in applying to proposed
      dental hygiene doctoral degree programs. A second-request was sent 1 month later
      to capture non-responders. Frequencies and cross-tabulations of responses were
      analyzed using the online software program, Qualtrics.TM RESULTS: Of the 255
      graduate learners enrolled in 2014 reported by dental hygiene program directors,
      159 completed the survey for a 62% response rate. The majority of respondents
      (77%) indicated that doctoral education in dental hygiene is needed for the
      advancement of the dental hygiene discipline and such programs are important to
      the dental hygiene profession (89%). Although most respondents supported both the
      PhD in dental hygiene and the Doctor of Dental Hygiene Practice (DDHP) degrees,
      more were interested in applying to a DDHP program (62%) than to a dental hygiene
      PhD program (38%). In addition, 43% expressed interest in enrolling in a doctoral
      degree program in the next 1 to 5 years and most preferred a hybrid online/onsite
      program format. The most frequently reported reasons for pursing a doctoral
      degree were: to become a better teacher, to expand clinical practice
      opportunities, to become a better researcher and to increase salary. CONCLUSION:
      Most dental hygiene master degree learners in this study believed doctoral dental
      hygiene education is needed and important to the dental hygiene discipline and
      profession, and were interested in applying to such programs. Future research is
      needed in this area.

PMID- 26304946
TI  - Knowledge, Perceived Ability and Practice Behaviors Regarding Oral Health among
      Pediatric Hematology and Oncology Nurses.
AB  - PURPOSE: Oral complications are common in children undergoing head and neck
      radiation and chemotherapy. The purpose of this study is to examine the
      knowledge, perceived ability and practice behaviors of pediatric oncology and
      hematology nurses in assisting with the various oral health care needs of
      pediatric oncology patients and to identify pediatric oncology nurses' previous
      training/education, practice types and other demographic characteristics that are
      related to their oral health competencies. METHODS: A survey of a convenience
      sample of Pediatric Oncology and Hematology Nurses was conducted during the
      Association of Pediatric Oncology and Hematology Nurses' (APHON) 36(th) Annual
      Conference and Exhibit. Descriptive analysis and the exploratory factor analyses
      were performed using SAS version 9.2 (SAS Institute, Inc., Cary, NC). RESULTS:
      Among the 300 surveys that were distributed, 235 surveys were completed (78%
      response rate) by pediatric oncology or hematology nurses who provide direct
      patient care in the U.S. Approximately 75% reported receiving less than 3 hours
      of oral health related education/training. Sixty percent did not have a clinical
      requirement regarding the assessment of the teeth and gums during their nursing
      school education. Bivariate analyses indicated that nurses who had clinical
      requirements regarding oral health assessment during nursing education/training
      presented greater overall oral health competencies including having greater
      confidence in examining oral complications than those who did not. CONCLUSION:
      Pediatric oncology nurses' knowledge, perceived ability and practice in assisting
      patient's oral hygiene care, preventing and managing oral complications vary by
      topic and might reflect their educational preparedness. This study may provide
      valuable information pertaining to the need and opportunity for interprofessional
      oral health care education and collaboration with nursing and dental
      professionals, in order to increase access to comprehensive oral care for
      pediatric cancer patients.

PMID- 26304947
TI  - Oral Care in the Long-Term Care of Older Patients: How Can the Dental Hygienist
      Meet the Need?
AB  - PURPOSE: It is estimated that the older population, aged 65 and older, will make
      up over 20% of the U.S. population by the year 2030. Research acknowledges about
      4% of the older population resides in long-term care facilities (LTCFs), where
      the long-term older patient (LTOP) is under the formal supervised care or custody
      of institutions with skilled nurses. By the year 2040, 4 million geriatric
      residents are predicted to move into LTCFs in the U.S. In 2000, the Surgeon
      General reported LTOPs in LTCFs have greater oral hygiene needs than any other
      segment of the population to include: root caries, periodontal disease,
      xerostomia, fungal infections and other oral health concerns. Serious systemic
      health conditions occurring at high incidence rates have been linked to poor oral
      hygiene in the LTOP. The purpose of this manuscript is to identify systemic
      health conditions, oral health conditions, barriers to oral care for LTOPs and to
      offer recommendations for increased access to care within LTCFs through the use
      of registered dental hygienists (RDHs).

PMID- 26304948
TI  - Technical Performance of Universal and Enhanced Intraoral Imaging Rectangular
      Collimators.
AB  - PURPOSE: The purpose of this study was to compare the number and type of
      technical errors between 2 rectangular collimators, time/motion effort and
      radiographer preference. METHODS: Subjects (n=17) were recruited to expose an 18
      projection full mouth series (FMX) using Tru-AlignTM (enhanced) and Rinn(r)
      (universal) collimator devices. Both FMXs were exposed using photostimulable
      phosphor (PSP) digital sensors on a DXTTR manikin with an intraoral x-ray unit. A
      5-question survey evaluated ease of device use, time required and device
      preference. Data were analyzed using frequencies, paired t-test, ANOVA and least
      squares means using a general linear model. RESULTS: A lower mean number of
      technique errors per FMX occurred with the enhanced device (9.7) compared to the
      universal device (12.1). Collimator centering errors occurred 3-times more often
      with the universal device. The mean numbers of diagnostically unacceptable errors
      per FMX were similar (Universal=3.2 vs Enhanced=2.9). The least squares means
      adjusted model showed a statistically significant difference of errors between
      the 2 devices (p=0.0478) and errors by location when comparing posterior to
      anterior and posterior to bitewing (p<0.0001). Subjects (94%) preferred the
      enhanced device and found it easier to use compared to the universal device.
      Significantly less time was needed to expose an FMX (4 min) when using the
      enhanced device (p=0.0001). CONCLUSION: The enhanced device enabled subjects to
      expose diagnostically acceptable radiographs more efficiently with fewer
      collimator centering errors; however, it does so with a 35% greater exposure area
      and a concomitant increase in patient dose.

PMID- 26304949
TI  - An Assessment Model for Evaluating Outcomes in Federally Qualified Health
      Centers' Dental Departments: Results of a 5 Year Study.
AB  - PURPOSE: The purpose of this report was to establish baseline data on 10 oral
      health performance indicators over 5 fiscal years (2007 to 2008 through 2011 to
      2012) for an Iowa health center. The baseline data provides an assessment model
      and reports outcomes based on the use of the model. Performance indicators show
      evidence of provider performance, accountability to stakeholders and provide the
      benchmarks required for dental management to develop future goals to improve oral
      health outcomes for at-risk populations. METHODS: Using descriptive statistic,
      this report extrapolated data from the Iowa Health Center's computer management
      systems software, HealthPro, and Centricity electronic medical records, and
      analyzed using IBM(r) SPSS(r) 19. This report describes the change in utilization
      for number and type of visits for uninsured and Medicaid patients over 5 fiscal
      years (a fiscal year is measured from November 1 through October 31). RESULTS:
      The number of patients receiving at least 1 dental visit in a measurement year
      showed n=81,673 procedures with 21% (17,167) being unduplicated patients.
      Preventive averaged 46%, restorative 18%, urgent care 22% and other procedures
      14%. CONCLUSION: Federally qualified health centers (FQHCs) with a dental
      component serve populations with the greatest health disparities. This population
      includes ethnic and racial minorities, uninsured, underinsured, rural residents,
      Medicaid and Medicare. Establishing baseline data for FQHCs provides a
      foundational tool that will allow dental management to analyze successes as well
      as deficiencies in the goal to provide increased utilization to oral health care
      for at-risk populations.

PMID- 26304950
TI  - Evaluating Utility Gloves as a Potential Reservoir for Pathogenic Bacteria.
AB  - PURPOSE: This pilot study sought to determine the rate and degree to which gram
      negative Klebsiella pneumoniae, Escherichia coli and Pseudomonas aeruginosa and
      gram-positive Staphylococcus aureus occurred on the inside of utility gloves used
      at University of Maine at Augusta, Dental Health Programs' dental hygiene clinic.
      METHODS: Five steam autoclave utility gloves were randomly selected to serve as
      control and a convenience sample of 10 used utility gloves were selected from the
      sterilization area. A sample was collected from a predetermined surface area from
      the inside of each steam autoclave utility glove and used utility glove. Each
      sample was used to inoculate a Petri plate containing 2 types of culture media.
      Samples were incubated at 37 degrees  C for 30 to 36 hours in aerobic conditions.
      Colony forming units (CFU) were counted. RESULTS: Confidence intervals (CI)
      estimated the rate of contamination with gram-negative K. pneumoniae, E. coli and
      P. aeruginosa on the inside of steam autoclave utility gloves to be n=33 95% CL
      [0.000, 0.049], used utility gloves to be n=70, 95% CL [0.000, 0.0303]. Data
      estimated the rate of contamination with gram-positive S. aureus on the inside of
      steam autoclave utility gloves to be n=35, 95% CL [0.233, 0.530], used utility
      gloves to be n=70, 95% CL [0.2730, 0.4975]. Culture media expressed a wide range
      of CFU from 0 to over 200. CONCLUSION: The risk of utility glove contamination
      with gram-negative bacteria is likely low. The expressed growth of S. aureus from
      steam autoclave utility gloves controls raises questions about the effectiveness
      and safety of generally accepted sterilization standards for the governmentally
      mandated use of utility gloves.

PMID- 26304951
TI  - A Survey of Clinical Faculty Calibration in Dental Hygiene Programs.
AB  - PURPOSE: This study investigated the calibration efforts of entry-level dental
      hygiene programs in the U.S. Four aspects were explored, including attitudes,
      characteristics, quality and satisfaction, to evaluate current calibration
      practices. METHODS: A descriptive comparative survey design was used. Directors
      of accredited dental hygiene programs (n=345) were asked to forward an electronic
      survey invitation to clinical faculty. Eighty-five directors forwarded the survey
      to 847 faculty; 45.3% (n=384) participated. The 37-item survey contained multiple
      choice and Likert scale questions and was available for 3 weeks. Descriptive
      statistics were used to analyze demographic data and research questions. The
      Kruskal-Wallis, Spearman Correlation Coefficient and Mann-Whitney U tests were
      employed to analyze hypotheses (p=0.05). RESULTS: The demographic profile for
      participants revealed that most worked for institutions awarding associate entry
      level degrees, had 1 to 10 years' experience, taught clinically and didactically,
      and held a master's degree. Clinical instructors valued calibration, believed it
      reduced variation and wanted more calibration. Some were not offered quality
      calibration. There was a difference between the entry-level degree awarded and
      the program's evaluation of clinical skill faculty reliability, as analyzed using
      the Kruskal-Wallis test (p=0.008). Additionally, full-time versus part-time
      educators reported more observed student frustration with faculty variance, as
      evaluated using the Mann-Whitney U test (p=0.001, bfp=0.004). CONCLUSION: Faculty
      members value calibration's potential benefits and want enhanced calibration
      efforts. Calibration efforts need to be improved to include standards for
      measuring intra- and inter-rater reliability and plans for resolving
      inconsistencies. More research is needed to determine effective calibration
      methods and their impact on student learning.

PMID- 26304952
TI  - Dental Fear and Delayed Dental Care in Appalachia-West Virginia.
AB  - PURPOSE: The people of Appalachia-West Virginia are culturally unique and are
      known to have oral health disparities. The purpose of this study was to evaluate
      dental fear in relation to delayed dental care as a factor influencing oral
      health behaviors within this culture. METHODS: A cross sectional study design was
      used. Participants were urgent care patients in a university dental clinic. The
      sample included 140 adults over age 18 years. The Dental Fear Survey was used to
      determine dental fear level. Self-report of delayed dental care was provided by
      the participants. The Dental Fear Survey was dichotomized at score 33, with
      higher scores indicating dental fear. RESULTS: The prevalence of dental fear was
      47.1% (n=66). There was a significant association of dental fear and dental
      delay. The unadjusted odds ratio was 2.87 (95% CI: 1.17, 7.04; p=0.021). The
      adjusted odds ratio was 3.83 (95%CI: 1.14, 12.82; p=0.030), controlling for
      tobacco use, perceived oral health status, pain, and last dental visit. A
      difference in dental delay between men and women was not present in this sample.
      The only significant variable in delayed dental care was dental fear. CONCLUSION:
      In Appalachia-West Virginia, there remains a high level of dental fear, despite
      advances in dental care, techniques, and procedures.

PMID- 26304953
TI  - Distributed Circuit Plasticity: New Clues for the Cerebellar Mechanisms of
      Learning.
AB  - The cerebellum is involved in learning and memory of sensory motor skills.
      However, the way this process takes place in local microcircuits is still
      unclear. The initial proposal, casted into the Motor Learning Theory, suggested
      that learning had to occur at the parallel fiber-Purkinje cell synapse under
      supervision of climbing fibers. However, the uniqueness of this mechanism has
      been questioned, and multiple forms of long-term plasticity have been revealed at
      various locations in the cerebellar circuit, including synapses and neurons in
      the granular layer, molecular layer and deep-cerebellar nuclei. At present, more
      than 15 forms of plasticity have been reported. There has been a long debate on
      which plasticity is more relevant to specific aspects of learning, but this
      question turned out to be hard to answer using physiological analysis alone.
      Recent experiments and models making use of closed-loop robotic simulations are
      revealing a radically new view: one single form of plasticity is insufficient,
      while altogether, the different forms of plasticity can explain the multiplicity
      of properties characterizing cerebellar learning. These include multi-rate
      acquisition and extinction, reversibility, self-scalability, and generalization.
      Moreover, when the circuit embeds multiple forms of plasticity, it can easily
      cope with multiple behaviors endowing therefore the cerebellum with the
      properties needed to operate as an effective generalized forward controller. 

PMID- 26304954
TI  - Electrolyte depletion syndrome (McKittrick-Wheelock syndrome) successfully
      treated by endoscopic submucosal dissection.
AB  - A 66-year-old woman presented to us with malaise, anorexia and rectal mucous
      discharge, and her laboratory data showed severe hyponatremia, hypokalemia,
      hypochloremia and renal failure. Computed tomography revealed massive occupation
      of the rectum by a large tumor. Colonoscopy revealed a mucus-rich villous tumor
      in the rectum. As there were no other factors that could cause an electrolyte
      disorder, she was diagnosed with McKittrick-Wheelock syndrome (MWS). The current
      standard treatment for MWS is partial surgical colectomy. However, surgeries are
      invasive and postoperative complications sometimes become an issue. After
      confirming no signs of submucosal invasion of the tumor by magnifying
      chromoendoscopic examination, endoscopic submucosal dissection (ESD) was
      indicated. The tumor was completely removed en bloc without adverse events. The
      histology showed a mucosal adenocarcinoma containing a villous component, 24.5 x
      17.0 cm in size. This removal dramatically improved the patient's symptoms and
      the electrolyte abnormalities without medication. Although several sessions of
      endoscopic balloon dilation were required to treat postoperative stricture, she
      has been symptom-free and had no recurrence for 4 years after treatment. We
      experienced a case of MWS treated by ESD instead of surgery. ESD should be
      feasible and beneficial for the treatment of MWS.

PMID- 26304955
TI  - Adopting new gamma cameras and reconstruction algorithms: Do we need to re
      establish normal reference values?
AB  - BACKGROUND: The impact of adopting new single photon emission computed tomography
      (SPECT) cameras and new reconstruction algorithms on left ventricular (LV)
      volumes has not been well established. We sought to understand the impact of
      hardware and software changes on normal LV reference ranges. METHODS: Consecutive
      patients who underwent stress Tc-99m tetrofosmin 8-frame gated SPECT MPI were
      screened. Patients with a history of myocardial infarction, coronary
      revascularization, abnormal MPI, or known LV dysfunction/reduced ejection
      fraction were excluded. A total of 1953 consecutive normal patients, with rest LV
      end-diastolic volume (EDV) and end-systolic volume (ESV) measurements were
      analyzed. After stratifying according to sex, LV volumes indexed to body surface
      area were compared across the different gamma cameras. RESULTS: In a normal
      population, measurements with CZT were different from those obtained by the dual
      headed NaI gamma cameras for LV EDVi (men: 53.6 +/- 10.4 vs 48.3 +/- 10.2 mL/m(2)
      and women: 43.3 +/- 8.9 vs 37.8 +/- 9.3 mL/m(2); P < 0.001) and LV ESVi (men:
      21.7 +/- 7.0 vs 16.9 +/- 6.2 mL/m(2) and women: 13.4 +/- 5.3 vs 10.6 +/- 4.7
      mL/m(2); P < 0.001). Inter- and intra-observer reliability for all measures was
      excellent. These findings were verified in a prospectively collected cohort. A
      sub-analysis of LV measurements comparing new resolution recovery and standard
      reconstruction software revealed no significant differences in LV measures.
      CONCLUSION: This study demonstrates that normal references ranges of LV volumes
      vary between SPECT cameras and confirms the need for establishing reference
      values that are camera specific.

PMID- 26304956
TI  - Appropriate use criteria for SPECT myocardial perfusion imaging: Are they
      appropriate for women?
AB  - BACKGROUND: Several studies have reported that women are more likely to receive
      inappropriate SPECT myocardial perfusion imaging (MPI), suggesting gender
      disparity in AUC determination. We investigated the impact of gender on the
      diagnostic and prognostic utility of AUC. METHODS AND RESULTS: We analyzed a
      multi-site prospective cohort of 1511 consecutive patients (43.5% women) who
      underwent outpatient, community-based SPECT-MPI. Subjects were stratified into
      gender groups and appropriateness subgroups, and followed for 27 +/- 10 months
      for cardiac death, myocardial infarction, and coronary revascularization. Women
      were more likely to receive inappropriate MPI (60.7% vs 33.8%, P < .001).
      Irrespective of appropriateness, women were less likely to have an abnormal MPI
      (6.1% vs 14.9%, P < .001), even after adjusting for clinical covariates [odds
      ratio = 0.40 (95% confidence interval = 0.26-0.60), P < .001]. Irrespective of
      appropriateness, women were at lower risk for MACE (composite of cardiac death,
      myocardial infarction, or coronary revascularization) after adjusting for
      clinical and imaging covariates [hazard ratio = 0.49 (95% confidence interval =
      0.28-0.86), P = .01]. There was no interaction between gender and appropriateness
      group as a determinant of abnormal MPI or MACE (interaction P values >= .26),
      indicating that female gender was associated with similar relative risk of an
      abnormal MPI and MACE irrespective of appropriateness group. Abnormal MPI was
      similarly predictive of increased hazard of MACE in both genders, regardless of
      appropriateness (interaction P values >= .46). CONCLUSION: In this multi-site
      cohort, there was no demonstrable gender-based differential impact of AUC on the
      diagnostic or prognostic utility of SPECT-MPI. The study validates the methods
      used in determining risk in the AUC algorithm and endorses the widespread
      application of AUC in men and women.

PMID- 26304957
TI  - Highlights of the 12th International Conference on Nuclear Cardiology and Cardiac
      CT.

PMID- 26304958
TI  - Ambulatory Aortic Stiffness Is Associated With Narrow Retinal Arteriolar Caliber
      in Hypertensives: The SAFAR Study.
AB  - BACKGROUND: Arterial stiffness measured under static conditions reclassifies
      significantly cardiovascular (CV) risk and associates with narrower retinal
      arterioles. However, arterial stiffness exhibits circadian variation, thus single
      static stiffness recordings do not correspond to the "usual" 24 hr, awake, and
      asleep average arterial stiffness. We aimed to test the hypothesis that
      ambulatory 24 hr, awake, and asleep aortic (a) pulse wave velocity (PWV)
      associate with retinal vessel calibers, independently of confounders and of
      static arterial stiffness, in hypertensive individuals free from diabetes and CV
      disease. METHODS: Digital retinal images were obtained (181 individuals, age:
      53.9+/-10.7 years, 55.2% men) and retinal vessel calibers were measured with
      validated software to determine central retinal arteriolar and venular
      equivalents (CRAE and CRVE, respectively); ambulatory (24 hr, awake, asleep) and
      static office aPWV were estimated by Mobil-O-Graph; and static office carotid to
      femoral (cf) PWV by SphygmoCor. RESULTS: Regression analysis performed in 320
      gradable retinal images showed that, after adjustment for confounders: (i)
      ambulatory aPWV was significantly associated with narrower retinal arterioles but
      not with venules; (ii) asleep aPWV had stronger associations with CRAE than awake
      aPWV; (iii) both ambulatory aPWV and cfPWV were associated mutually independently
      with narrower retinal arterioles; aPWV introduction in the model of cfPWV,
      improved model's R2 (P = 0.012). Similar discriminatory ability of 24 hr aPWV and
      of cfPWV to detect the presence of retinal arteriolar narrowing was found.
      CONCLUSION: Ambulatory aPWV, estimated by an operator-independent method,
      provides additional information to cfPWV regarding the associations of arterial
      stiffness with the retinal vessel calibers.

PMID- 26304959
TI  - EETs Elicit Direct Increases in Pulmonary Arterial Pressure in Mice.
AB  - OBJECTIVE: The biological role of epoxyeicosatrienoic acids (EETs) in the
      regulation of pulmonary circulation is currently under debate. We hypothesized
      that EETs initiate increases in right ventricular systolic pressure (RVSP) via
      perhaps, pulmonary vasoconstriction. METHODS: Mice were anesthetized with
      isoflurane. Three catheters, inserted into the left jugular vein, the left
      carotid artery, and the right jugular vein, were used for infusing EETs,
      monitoring blood pressure (BP), and RVSP respectively. BP and RVSP were
      continuously recorded at basal conditions, in response to administration of 4
      regioisomeric EETs (5,6-EET; 8,9-EET; 11,12-EET, and 14,15-EET; 1, 2, 5 and 10
      ng/g body weight (BW) for each EET), and during exposure of mice to hypoxia.
      RESULTS: All 4 EETs initiated dose-dependent increases in RVSP, though reduced
      BP. 11,12-EET elicited the greatest increment in RVSP among all EET isoforms. To
      clarify the direct elevation of RVSP in a systemic BP-independent manner,
      equivalent amounts of 14,15-EET were injected over 1 and 2 minutes respectively.
      One-minute injection of 14,15-EET elicited significantly faster and greater
      increases in RVSP than the 2-minute injection, whereas their BP changes were
      comparable. Additionally, direct injection of low doses of 14,15-EET (0.1, 0.2,
      0.5, and 1 ng/g BW) into the right ventricle caused significant increases in RVSP
      without effects on BP, confirming that systemic vasodilation-induced increases in
      venous return are not the main cause for the increased RVSP. Acute exposure of
      mice to hypoxia significantly elevated RVSP, as well as 14,15-EET-induced
      increases in RVSP. CONCLUSIONS: EETs directly elevate RVSP, a response that may
      play an important role in the development of hypoxia-induced pulmonary
      hypertension (PH).

PMID- 26304960
TI  - PTH Is a Promising Auxiliary Index for the Clinical Diagnosis of Aldosterone
      Producing Adenoma.
AB  - BACKGROUND: Parathyroid hormone (PTH) stimulates aldosterone secretion in human
      adrenocortex and is regulated by the renin-angiotensin-aldosterone system. We
      speculated that measurement of PTH may be a valuable aid in the diagnosis of
      aldosterone-producing adenoma (APA). METHODS: To test this hypothesis, we
      recruited 142 patients with adrenal adenoma, of whom 84 had an APA and 58 had a
      nonfunctioning adrenal adenoma (NFA). Plasma levels of intact PTH, serum
      potassium, sodium, calcium, phosphate, 25(OH) vitamin D, plasma aldosterone
      concentration (PAC), plasma renin activity (PRA), and aldosterone to renin ratio
      (ARR) were measured in every patient. Computed tomography (CT) scanning of the
      adrenal gland and adrenal hormone levels was used to evaluate the function of the
      adrenal adenoma. We also evaluated the impact of renin-angiotensin-aldosterone
      system (RAAS) components on PTH from the recumbent-upright test in 15 patients
      with APA and 30 patients with NFA. RESULTS: Compared with NFA, PTH levels were
      significantly increased in patients with APA, and serum calcium and phosphate
      were significantly decreased. When position was changed from supine to upright,
      the variation in PTH levels was significantly higher in APA patients compared
      with NFA patients. Receiver operator characteristic (ROC) curves identified the
      Youden index, which corresponded to the best tradeoff of combined marker (ARR and
      PTH) with a sensitivity and specificity of 89.3% and 93.1%, respectively.
      CONCLUSIONS: The baseline and positional variation of serum PTH levels were
      significant in APA, thus PTH may be a promising auxiliary index for the clinical
      diagnosis of APA.

PMID- 26304961
TI  - Interactive Effect of the KCNJ11 Ile337Val Polymorphism and Cigarette Smoking on
      the Antihypertensive Response to Irbesartan in Chinese Hypertensive Patients.
AB  - OBJECTIVE: This study was designed to detect the association of the potassium
      inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene polymorphism
      with antihypertensive therapeutic response to irbesartan in a large-scale Chinese
      hypertensive population. METHODS: A total of 1,099 patients with essential
      hypertension were enrolled to receive a daily dose of 150 mg irbesartan for 27
      days. Pretreatment baseline blood pressure (BP) and posttreatment BP on the 28th
      day were measured. Plasma irbesartan concentrations were measured by high
      performance liquid chromatography-fluorescence. The KCNJ11 I337V gene
      polymorphism was determined using high-throughput TaqMan technology. RESULTS: The
      HapMap data in the Han Chinese population showed that the I337V was used as a
      representative for 4 common functional polymorphisms. Our results showed that the
      association of antihypertensive response to irbesartan and the KCNJ11 genetic
      variant in the total sample was not significant. However, in nonsmokers, relative
      to the GG genotype, subjects with the homozygous AA genotype had a significantly
      higher therapeutic response to irbesartan (adjusted beta +/- SE: 4.7+/-1.9 mm Hg,
      P = 0.015). In smokers, the subjects with the homozygous AA genotype had a
      significantly lower therapeutic response to irbesartan (adjusted beta +/- SE: 
      5.6+/-2.5 mm Hg, P = 0.026). A multivariate linear regression model confirmed
      that there was a significant interactive effect between the KCNJ11 gene and
      smoking on irbesartan treatment (interaction P = 0.001). CONCLUSION: The
      interactive effect of smoking status and the KCNJ11 genotype may influence the
      antihypertensive effects of irbesartan, which indicates a consideration for
      future individualized antihypertensive drug treatment.

PMID- 26304962
TI  - Anabolic Steroids Reduce Muscle Degeneration Associated With Rotator Cuff Tendon
      Release in Sheep.
AB  - BACKGROUND: Chronic rotator cuff tendon tearing is associated with irreversible
      atrophy, fatty infiltration, and interstitial fibrosis of the corresponding
      muscle. HYPOTHESES: Anabolic steroids can prevent musculotendinous degeneration
      during retraction and/or can reverse these changes after operative repair of the
      retracted musculotendinous unit in sheep. STUDY DESIGN: Controlled laboratory
      study. METHODS: The infraspinatus tendon was released in 18 alpine sheep. All
      sheep underwent repair of the retracted musculotendinous unit after 16 weeks and
      were sacrificed after 22 weeks; 6 sheep served as controls, 6 sheep were treated
      with weekly intramuscular injection of 150 mg of nandrolone decanoate after
      infraspinatus (ISP) repair (group N6W), and 6 sheep were treated with 150 mg of
      nandrolone decanoate immediately after tendon release (group N22W). Muscle biopsy
      specimens were taken before tendon release and after 16 and 22 weeks. Muscle
      volume and fatty infiltration (on MRI), myotendinous retraction, and muscle
      density (on computed tomography) were measured immediately after ISP release,
      after 6 weeks, and before ISP repair and sacrifice. RESULTS: Muscle volume on MRI
      decreased to a mean (+/-SD) of 80% +/- 8% of the original volume after 6 weeks,
      remained stable at 78% +/- 11% after 16 weeks, and decreased further to 69% +/-
      9% after 22 weeks in the control group. These findings were no different from
      those in group N22W (72% +/- 9% at 6 weeks, 73% +/- 6% at 16 weeks, and 67% +/-
      5% at 22 weeks). Conversely, the N6W group did not show a decrease in ISP volume
      after repair; this finding differed significantly from the response in the
      control and N22W groups. Fatty infiltration (on MRI) continuously increased in
      the control group (12% +/- 4% at tendon release, 17% +/- 4% after 6 weeks, 50% +/
      9% after 16 weeks, and 60% +/- 8% after 22 weeks) and the N6W group. However,
      application of anabolic steroids at the time of tendon release (N22W group)
      significantly reduced fatty infiltration after 16 (16% +/- 5%; P < .001) and 22
      weeks (22% +/- 7%; P < .001). CONCLUSION: In a sheep model of rotator cuff tendon
      tear, further muscle atrophy can be prevented with the application of anabolic
      steroids starting immediately after tendon repair. In addition, fatty muscle
      infiltration can largely be prevented if the steroids are applied immediately
      after tendon release. CLINICAL RELEVANCE: Study findings may lead to the
      development of treatment strategies to prevent or reduce muscle degeneration
      caused by rotator cuff tendon tearing.

PMID- 26304963
TI  - A novel mouse model identifies cooperating mutations and therapeutic targets
      critical for chronic myeloid leukemia progression.
AB  - The introduction of highly selective ABL-tyrosine kinase inhibitors (TKIs) has
      revolutionized therapy for chronic myeloid leukemia (CML). However, TKIs are only
      efficacious in the chronic phase of the disease and effective therapies for TKI
      refractory CML, or after progression to blast crisis (BC), are lacking. Whereas
      the chronic phase of CML is dependent on BCR-ABL, additional mutations are
      required for progression to BC. However, the identity of these mutations and the
      pathways they affect are poorly understood, hampering our ability to identify
      therapeutic targets and improve outcomes. Here, we describe a novel mouse model
      that allows identification of mechanisms of BC progression in an unbiased and
      tractable manner, using transposon-based insertional mutagenesis on the
      background of chronic phase CML. Our BC model is the first to faithfully
      recapitulate the phenotype, cellular and molecular biology of human CML
      progression. We report a heterogeneous and unique pattern of insertions
      identifying known and novel candidate genes and demonstrate that these pathways
      drive disease progression and provide potential targets for novel therapeutic
      strategies. Our model greatly informs the biology of CML progression and provides
      a potent resource for the development of candidate therapies to improve the
      dismal outcomes in this highly aggressive disease. 

PMID- 26304964
TI  - Cysteinyl leukotrienes mediate lymphokine killer activity induced by NKG2D and IL
      15 in cytotoxic T cells during celiac disease.
AB  - Eicosanoids are inflammatory mediators that play a key but incompletely
      understood role in linking the innate and adaptive immune systems. Here, we show
      that cytotoxic effector T cells (CTLs) are capable of both producing and
      responding to cysteinyl leukotrienes (CystLTs), allowing for the killing of
      target cells in a T cell receptor-independent manner. This process is dependent
      on the natural killer receptor NKG2D and exposure to IL-15, a cytokine induced in
      distressed tissues. IL-15 and NKG2D signaling drives the up-regulation of key
      enzymes implicated in the synthesis of CystLTs, as well as the expression of
      CystLT receptors, suggesting a positive feedback loop. Finally, although the
      CystLT pathway has been previously linked to various allergic disorders, we
      provide unexpected evidence for its involvement in the pathogenesis of celiac
      disease (CD), a T helper 1 cell-mediated enteropathy induced by gluten. These
      findings provide new insights into the cytolytic signaling pathway of NKG2D and
      the pathogenesis of organ-specific immune disorders. Furthermore, they suggest
      that the blockade of CystLT receptors may represent a potent therapeutic target
      for CD or potentially other autoimmune disorders in which NKG2D has been
      implicated. 

PMID- 26304965
TI  - Suppression of Th2 and Tfh immune reactions by Nr4a receptors in mature T reg
      cells.
AB  - Regulatory T (T reg) cells are central mediators of immune suppression. As such,
      T reg cells are characterized by a distinct pattern of gene expression, which
      includes up-regulation of immunosuppressive genes and silencing of inflammatory
      cytokine genes. Although an increasing number of transcription factors that
      regulate T reg cells have been identified, the mechanisms by which the T reg cell
      specific transcriptional program is maintained and executed remain largely
      unknown. The Nr4a family of nuclear orphan receptors, which we recently
      identified as essential for the development of T reg cells, is highly expressed
      in mature T reg cells as well, suggesting that Nr4a factors play important roles
      even beyond T reg cell development. Here, we showed that deletion of Nr4a genes
      specifically in T reg cells caused fatal systemic immunopathology. Nr4a-deficient
      T reg cells exhibited global alteration of the expression of genes which specify
      the T reg cell lineage, including reduction of Foxp3 and Ikzf4. Furthermore, Nr4a
      deficiency abrogated T reg cell suppressive activities and accelerated conversion
      to cells with Th2 and follicular helper T (Tfh) effector-like characteristics,
      with heightened expression of Th2 and Tfh cytokine genes. These findings
      demonstrate that Nr4a factors play crucial roles in mature T reg cells by
      directly controlling a genetic program indispensable for T reg cell maintenance
      and function. 

PMID- 26304967
TI  - Peer Coaches to Improve Diabetes Outcomes in Rural Alabama: A Cluster Randomized
      Trial.
AB  - PURPOSE: It is unclear whether peer coaching is effective in minority populations
      living with diabetes in hard-to-reach, under-resourced areas such as the rural
      South. We examined the effect of an innovative peer-coaching intervention plus
      brief education vs brief education alone on diabetes outcomes. METHODS: This was
      a community-engaged, cluster-randomized, controlled trial with primary care
      practices and their surrounding communities serving as clusters. The trial
      enrolled 424 participants, with 360 completing baseline and follow-up data
      collection (84.9% retention). The primary outcomes were change in glycated
      hemoglobin (HbA1c), systolic blood pressure (BP), low density lipoprotein
      cholesterol (LDL-C), body mass index (BMI), and quality of life, with diabetes
      distress and patient activation as secondary outcomes. Peer coaches were trained
      for 2 days in community settings; the training emphasized motivational
      interviewing skills, diabetes basics, and goal setting. All participants received
      a 1-hour diabetes education class and a personalized diabetes report card at
      baseline. Intervention arm participants were also paired with peer coaches; the
      protocol called for telephone interactions weekly for the first 8 weeks, then
      monthly for a total of 10 months. RESULTS: Due to real-world constraints, follow
      up was protracted, and intervention effects varied over time. The analysis that
      included the 68% of participants followed up by 15 months showed only a
      significant increase in patient activation in the intervention group. The
      analysis that included all participants who eventually completed follow-up
      revealed that intervention arm participants had significant differences in
      changes in systolic BP (P = .047), BMI (P = .02), quality of life (P = .003),
      diabetes distress (P = .004), and patient activation (P = .03), but not in HbA1c
      (P = .14) or LDL-C (P = .97). CONCLUSION: Telephone-delivered peer coaching holds
      promise to improve health for individuals with diabetes living in under-resourced
      areas.

PMID- 26304968
TI  - Contributions of Peer Support to Health, Health Care, and Prevention: Papers from
      Peers for Progress.
AB  - SUBSTANTIAL: evidence documents the benefits of peer support provided by
      community health workers, lay health advisors, promotores de salud, and others.
      The papers in this supplement, all supported by the Peers for Progress program of
      the American Academy of Family Physicians Foundation, contribute to the growing
      body of literature addressing the efficacy, effectiveness, feasibility, reach,
      sustainability, and adoption of peer support for diabetes self-management. They
      and additional papers supported by Peers for Progress contribute to understanding
      how peer support can be implemented in real world settings. Topics include
      examination of the peers who provide peer support, reaching the hardly reached,
      success factors in peer support interventions, proactive approaches, attention to
      emotions, peer support in behavioral health, dissemination models and their
      application in China, peer support in the patient-centered medical home, research
      challenges, and policy implications. 

PMID- 26304969
TI  - Peer-Led, Empowerment-Based Approach to Self-Management Efforts in Diabetes
      (PLEASED): A Randomized Controlled Trial in an African American Community.
AB  - PURPOSE: We compared a 3-month diabetes self-management education (DSME) program
      followed by a 12-month peer support intervention with a 3-month DSME program
      alone in terms of initial and sustained improvements in glycated hemoglobin
      (HbA1c). Secondary outcomes were risk factors for cardiovascular disease (CVD),
      diabetes distress, and social support. METHODS: We randomized 106 community
      dwelling African American adults with type 2 diabetes to a 3-month DSME program
      followed by 12 months of weekly group sessions and supplementary telephone
      support delivered by peer leaders or to a 3-month DSME program with no follow-up
      peer support. Assessments were conducted at baseline, 3, 9, and 15 months.
      RESULTS: No changes in HbA1c were observed at 3 months or at 15 months for either
      group. The peer support group either sustained improvement in key CVD risk
      factors or stayed the same while the control group worsened at 15 months. At 15
      months, the peer-support group had significantly lower low-density lipoprotein
      cholesterol levels (-15 mg/dL, P = .03), systolic blood pressure (-10 mm Hg, P =
      .01), diastolic blood pressure (-8.3 mm Hg, P = .001), and body mass index (-0.8
      kg/m(2), P = .032) than the DSME-alone group. CONCLUSIONS: In this population of
      African American adults, an initial DSME program, whether or not followed by 12
      months of peer support, had no effect on glycemic control. Participants in the
      peer-support arm of the trial did, however, experience significant improvements
      in some CVD risk factors or stay approximately the same while the control group
      declined.

PMID- 26304966
TI  - Human TYK2 deficiency: Mycobacterial and viral infections without hyper-IgE
      syndrome.
AB  - Autosomal recessive, complete TYK2 deficiency was previously described in a
      patient (P1) with intracellular bacterial and viral infections and features of
      hyper-IgE syndrome (HIES), including atopic dermatitis, high serum IgE levels,
      and staphylococcal abscesses. We identified seven other TYK2-deficient patients
      from five families and four different ethnic groups. These patients were
      homozygous for one of five null mutations, different from that seen in P1. They
      displayed mycobacterial and/or viral infections, but no HIES. All eight TYK2
      deficient patients displayed impaired but not abolished cellular responses to (a)
      IL-12 and IFN-alpha/beta, accounting for mycobacterial and viral infections,
      respectively; (b) IL-23, with normal proportions of circulating IL-17(+) T cells,
      accounting for their apparent lack of mucocutaneous candidiasis; and (c) IL-10,
      with no overt clinical consequences, including a lack of inflammatory bowel
      disease. Cellular responses to IL-21, IL-27, IFN-gamma, IL-28/29 (IFN-lambda),
      and leukemia inhibitory factor (LIF) were normal. The leukocytes and fibroblasts
      of all seven newly identified TYK2-deficient patients, unlike those of P1,
      responded normally to IL-6, possibly accounting for the lack of HIES in these
      patients. The expression of exogenous wild-type TYK2 or the silencing of
      endogenous TYK2 did not rescue IL-6 hyporesponsiveness, suggesting that this
      phenotype was not a consequence of the TYK2 genotype. The core clinical phenotype
      of TYK2 deficiency is mycobacterial and/or viral infections, caused by impaired
      responses to IL-12 and IFN-alpha/beta. Moreover, impaired IL-6 responses and HIES
      do not appear to be intrinsic features of TYK2 deficiency in humans. 

PMID- 26304970
TI  - Are Low-Income Peer Health Coaches Able to Master and Utilize Evidence-Based
      Health Coaching?
AB  - PURPOSE: A randomized controlled trial found that patients with diabetes had
      lower HbA1c levels after 6 months of peer health coaching than patients who did
      not receive coaching. This paper explores whether the peer coaches in that trial,
      all low-income patients with diabetes, mastered and utilized an evidence-based
      health coaching training curriculum. The curriculum included 5 core features: ask
      tell-ask, closing the loop, know your numbers, behavior-change action plans, and
      medication adherence counseling. METHODS: This paper includes the results of
      exams administered to trainees, exit surveys performed with peer coaches who
      completed the study and those who dropped out, observations of peer coaches
      meeting with patients, and analysis of in-depth interviews with peer coaches who
      completed the study. RESULTS: Of the 32 peer coach trainees who completed the
      training, 71.9% lacked a college degree; 25.0% did not graduate from high school.
      The 26 trainees who passed the exams attended 92.7% of training sessions compared
      with 80.6% for the 6 trainees who did not pass. Peer coaches who completed the
      study wanted to continue peer coaching work and had confidence in their abilities
      despite their not consistently employing the coaching techniques with their
      patients. Quotations describe coaches' perceptions of the training. CONCLUSIONS:
      Of low-income patients with diabetes who completed the evidenced-based health
      coaching training, 81% passed written and oral exams and became effective peer
      health coaches, although they did not consistently use the techniques taught.

PMID- 26304971
TI  - Effects of Providing Peer Support on Diabetes Management in People With Type 2
      Diabetes.
AB  - PURPOSE: We examined the effects of participating in a "train-the-trainer"
      program and being a peer supporter on metabolic and
      cognitive/psychological/behavioral parameters in Chinese patients with type 2
      diabetes. METHODS: In response to our invitation, 79 patients with fair glycemic
      control (HbA1c <8%) agreed to participate in a "train-the-trainer" program to
      become peer supporters. Of the 59 who completed the program successfully, 33
      agreed to be peer supporters ("agreed trainees") and were each assigned to
      support 10 patients for 1 year, with a voluntary extension period of 3 additional
      years, while 26 trainees declined to be supporters ("refused trainees"). A group
      of 60 patients with fair glycemic control who did not attend the training program
      and were under usual care were selected as a comparison group. The primary
      outcome was the change in average HbA1c levels for the 3 groups from baseline to
      6 months. RESULTS: At 6 months, HbA1c was unchanged in the trainees (at baseline,
      7.1 +/- 0.3%; at 6 months, 7.1 +/- 1.1%) but increased in the comparison group
      (at baseline, 7.1 +/- 0.5%; at 6 months, 7.3 +/- 1.1%. P = .02 for between-group
      comparison). Self-reported self-care activities including diet adherence and foot
      care improved in the trainees but not the comparison group. After 4 years, HbA1c
      remained stable among the agreed trainees (at baseline, 7.0 +/- 0.2%; at 4 years:
      7.2 +/- 0.6%), compared with increases in the refused trainees (at baseline, 7.1
      +/- 0.4%; at 4 years, 7.8 +/- 0.8%) and comparison group (at baseline, 7.1 +/-
      0.5%; at 4 years, 8.1 +/- 0.6%. P = .001 for between-group comparison).
      CONCLUSIONS: Patients with diabetes who engaged in providing ongoing peer support
      to other patients with diabetes improved their self-care while maintaining
      glycemic control over 4 years.

PMID- 26304972
TI  - Peer Support for Diabetes Management in Primary Care and Community Settings in
      Anhui Province, China.
AB  - PURPOSE: We evaluated a peer leader-support program (PLSP) for diabetes self
      management in China in terms of acceptability and feasibility; implementation;
      perceived advantages; disadvantages and barriers; reach and recruitment;
      effectiveness in terms of diabetes knowledge and clinical impacts; adoption; and
      sustainability. METHODS: Within each of 3 cities in Anhui Province, 2
      subcommunities were randomly assigned to usual care or PLSP. Peer leaders and
      staff of Community Health Service Centers (CHSCs) co-led biweekly educational
      meetings. Peer leaders also led biweekly discussion meetings, promoted regular
      care through the CHSCs, organized informal health promotion activities (eg,
      walking and tai chi groups), and provided informal individual support to
      participants through casual contact. RESULTS: Qualitative evaluations indicated
      acceptance of and positive responses to the program among patients, peer leaders,
      and CHSC staff. Implementation was successful in 2 of 3 subcommunities, the third
      failing for lack of staff resources. Reported advantages included peer support as
      a bridge between CHSCs and their patients. In 2 sites where the PLSP was
      implemented, analyses controlling for baseline differences and site showed
      significant benefits for PLSP relative to controls (P <0.05) for knowledge, self
      efficacy, BMI, systolic blood pressure, diastolic blood pressure, and both
      fasting and 2-hour post-prandial blood glucose. The Anhui Provincial Health
      Bureau has extended the PLSP model to other communities and to cardiovascular
      disease prevention and management. CONCLUSION: The PLSP was well accepted,
      feasible given sufficient administrative and staff resources, effective for those
      who participated, and generalizable to other sites and health problems.

PMID- 26304974
TI  - Challenges of Prolonged Follow-up and Temporal Imbalance in Pragmatic Trials:
      Analysis of the ENCOURAGE Trial.
AB  - PURPOSE: Peer support intervention trials are typically conducted in community
      based settings and provide generalizable results. The logistic challenges of
      community-based trials often result in unplanned temporal imbalances in
      recruitment and follow-up. When imbalances are present, as in the ENCOURAGE
      trial, appropriate statistical methods must be used to account for these
      imbalances. We present the design, conduct, and analysis of the ENCOURAGE trial
      as a case study of a cluster-randomized, community-based, peer-coaching
      intervention. METHODS: Preliminary data analysis included examination of study
      data for imbalances in participant characteristics at baseline, the presence of
      both secular and seasonal trends in outcome measures, and imbalances in time from
      baseline to follow-up. Additional examination suggested the presence of nonlinear
      trends in the intervention effect. The final analyses adjusted for all identified
      imbalances with accounting for community clustering by supplementing linear mixed
      effect models with generalized additive mixed models (GAMM) to examine nonlinear
      trends. RESULTS: Largely due to the location of participants across a
      considerable geographic area, temporal imbalances were discovered in recruitment,
      baseline, and follow-up data collection, along with evidence for both secular and
      seasonal trends in study outcome measures. Using the standard analytical
      approach, ENCOURAGE appeared to be a null trial. After incorporating adjustment
      for these temporal imbalances, linear regression analyses still showed no
      intervention effect. Upon further analyses using GAMM to consider nonlinear
      intervention trends, we observed intervention effects that were both significant
      (P <.05) and nonlinear. DISCUSSION: In community-based trials, recruitment and
      follow-up may not occur as planned, and complex temporal imbalance may greatly
      influence the analysis. Real-world trials should use careful logistic planning
      and monitoring to avoid temporal imbalance. If imbalance is unavoidable,
      sophisticated statistical methods may nevertheless extract useful information,
      although the potential problem of residual confounding due to other unmeasured
      imbalances must be considered.

PMID- 26304973
TI  - What Peer Mentoring Adds to Already Good Patient Care: Implementing the Carpeta
      Roja Peer Mentoring Program in a Well-Resourced Health Care System.
AB  - PURPOSE: The purpose of this study was to evaluate the impact of a peer support
      program on the health outcomes of patients already receiving well-organized,
      comprehensive diabetes care. METHODS: We used a mixed-methods, nonrandomized,
      control-group design to evaluate the impact of a peer-mentoring program on the
      health outcomes and self-management behaviors of adults with type 2 diabetes in
      15 primary care practices in San Antonio. Propensity score analysis, t-tests, and
      multivariable repeated analyses were used to evaluate impact. Qualitative
      interviews were conducted with 15 participants in the intervention group and
      analyzed using a grounded theory approach. RESULTS: Both intervention and control
      groups showed significant improvement on all health indicators from baseline to 6
      month follow-up (P<.001). Hemoglobin A1c (HbA1c) decreased slightly faster for
      patients in the intervention group (P=.04). Self-management behaviors improved
      significantly from baseline to 6-month follow-up for the intervention group.
      Interviewed participants also reported reductions in social isolation and
      extension of impact of health behavior changes to multiple generations of family
      members. CONCLUSIONS: The addition of peer mentoring to already well-organized
      comprehensive diabetes care does not improve outcomes. However, findings suggest
      that the impact of the program extends to members of the participants' families,
      which is an intriguing finding that deserves further study.

PMID- 26304975
TI  - Enriching Patient-Centered Medical Homes Through Peer Support.
AB  - Peer supporters are recognized by various designations-community health workers,
      promotores de salud, lay health advisers-and are community members who work for
      pay or as volunteers in association with health care systems or nonprofit
      community organizations and often share ethnicity, language, and socioeconomic
      status with the mentees that they serve. Although emerging evidence demonstrates
      the efficacy of peer support at the community level, the adoption and
      implementation of this resource into patient-centered medical homes (PCMHs) is
      still under development. To accelerate that integration, this article addresses
      three major elements of peer support interventions: the functions and features of
      peer support, a framework and programmatic strategies for implementation, and
      fiscal models that would support the sustained viability of peer support programs
      within PCMHs. Key functions of peer support include assistance in daily
      management of health-related behaviors, social and emotional support, linkage to
      clinical care, and longitudinal or ongoing support. An organizational model of
      innovation implementation provides a useful framework for determining how to
      implement and evaluate peer support programs in PCMHs. Programmatic strategies
      that can be useful in developing peer support programs within PCMHs include peer
      coaching or mentoring, group self-management training, and programs designed
      around the telephone and information technology. Fiscal models for peer support
      programs include linkages with hospital or health care systems, service- or
      community-based nonprofit organizations, and partnerships between health care
      systems and community groups. Peer support promises to enrich PCMHs by activating
      patients in their self-care, providing culturally sensitive outreach, and opening
      the way for partnerships with community-based organizations.

PMID- 26304976
TI  - Challenges in the Ethical Review of Peer Support Interventions.
AB  - PURPOSE: Ethical review processes have become increasingly complex. We have
      examined how 8 collaborating diabetes peer-support clinical trials were assessed
      by ethics committees. METHODS: The ethical reviews from the 8 peer-support
      studies were collated and subjected to a thematic analysis. We mapped the
      recommendations of local Institutional Review Boards and ethics committees onto
      the "4+1 ethical framework" (autonomy, beneficence, non-maleficence, and justice,
      along with concern for their scope of application). RESULTS: Ethics committees
      did not consistently focus on tasks within the 4+1 framework: many conducted
      reviews of scientific, organizational, and administrative activities. Of the 20
      themes identified across the ethical reviews, only 4 fell within the scope of the
      4+1 framework. Variation in processes and requirements for ethics committees were
      particularly evident between study countries. Some of the consent processes
      mandated by ethical review boards were disproportionate for peer support,
      increased participant burden, and reduced the practicality of testing an ethical
      intervention. Across the 8 studies, ethics committees' reviews included the
      required elements to ensure participant safety; however, they created a range of
      hurdles that in some cases delayed the research and required consent processes
      that could hinder the spontaneity and/or empathy of peer support. CONCLUSION:
      Ethics committees should avoid repeating the work of other trusted agencies and
      consider the ethical validity of "light touch" consent procedures for peer
      support interventions. The investigators propose an ethical framework for
      research on peer support.

PMID- 26304977
TI  - Puentes hacia una mejor vida (Bridges to a Better Life): Outcome of a Diabetes
      Control Peer Support Intervention.
AB  - PURPOSE: Peer support can promote diabetes control, yet research on feasible and
      effective peer support models is lacking. This randomized controlled trial tested
      a volunteer-based model of peer support for diabetes control. METHODS: Thirty
      four volunteer peer leaders were recruited and trained to provide support to 5 to
      8 patients each through telephone contact, in-person, individual, and group
      support. Planned dose was 8 contacts, preferably in the first 6 months. Patients
      with uncontrolled diabetes were randomly sampled from the medical records of 3
      community clinics. After a baseline interview and medical records review to
      obtain baseline values for the primary outcome, HbA1c, 336 patient participants
      were randomly assigned to a 12-month peer support intervention or usual care. The
      assessment protocol was repeated at 6 and 12 months after baseline. RESULTS:
      Thirty peer leaders delivered an average of 4 contacts each per assigned
      participant (range 1-24). Despite the lack of intervention fidelity, the
      intervention was effective at reducing glycated hemoglobin (HbA1c) among
      intervention as compared with usual care participants (P=0.05). Similar trends
      were observed in frequency of meeting fruit and vegetable guidelines (P =0.09), a
      secondary outcome. Counterintuitively, usual care participants reported checking
      their feet more days out of 7 than intervention participants (P =0.03).
      CONCLUSIONS: Given the modest changes we observed, combined with other evidence
      for peer support to promote diabetes control, additional research is needed on
      how to modify the system of care to increase the level of peer support delivered
      by volunteers.

PMID- 26304978
TI  - Air-Fed Visors Used for Isocyanate Paint Spraying--Potential Exposure When the
      Visor Is Lifted.
AB  - Continuous-flow air-supplied breathing apparatus with a visor is the respiratory
      protective equipment (RPE) of choice within the motor vehicle repair trade for
      protection against exposure to isocyanate paints. Whilst these devices are
      capable of providing adequate protection, a common workplace practice of sprayers
      lifting up the visor of their RPE immediately after spraying when checking the
      quality of the paint finish is thought to have an impact on the protection
      afforded. While the visor lift may be only for a few seconds, this action,
      especially if repeated numerous times during a work shift, could potentially
      result in a significant increase in exposure.Informal interviews with paint
      sprayers were conducted to understand the reasons for this behaviour followed by
      a series of laboratory tests to quantify the potential degree of exposure as a
      result of a visor lift.The majority of the paint sprayers interviewed explained
      their reasons for lifting their visors immediately after spraying and before the
      spray booth had been adequately cleared by ventilation. The main reasons given
      for a visor lift included a combination of habit, poor visibility due to poor
      visual clarity of the visor screen material, over spray, scratched visor screens,
      internal visor reflections, and poor booth lighting.The findings of the tests
      showed that the degree of protection provided by the visor when in the lifted
      position is in the approximate range of 1-3.7 (mean 1.7) and over the whole of
      the exposure period (from start of the lift to recovery of protection after
      refitting) is in the approximate range of 1.4-9.0 (mean 2.7). This is a
      significant reduction when compared to the assigned protection factor of 40 for
      this class of device and the measured protection factors of 5000-10 000 when worn
      correctly.These results clearly demonstrate that lifting the visor whilst still
      within a contaminated atmosphere considerably increases the wearer's exposure and
      that this is an example where improvements in RPE design can contribute to lower
      exposure.

PMID- 26304979
TI  - Gateway to deLiver: How malaria sporozoites cross the sinusoidal barrier.

PMID- 26304980
TI  - Skin-resident T cells keep parasites on a Leish.

PMID- 26304981
TI  - No "Kindlin," it's all about HSC balance.

PMID- 26304982
TI  - Inborn errors underlying herpes simplex encephalitis: From TLR3 to IRF3.

PMID- 26304984
TI  - Right care and high-value cardiology: doctors' responsibilities to the patient
      and the population.

PMID- 26304983
TI  - A Road Map for 21st Century Genetic Restoration: Gene Pool Enrichment of the
      Black-Footed Ferret.
AB  - Interspecies somatic cell nuclear transfer (iSCNT) could benefit recovery
      programs of critically endangered species but must be weighed with the risks of
      failure. To weigh the risks and benefits, a decision-making process that
      evaluates progress is needed. Experiments that evaluate the efficiency and
      efficacy of blastocyst, fetal, and post-parturition development are necessary to
      determine the success or failure or species-specific iSCNT programs. Here, we use
      the black-footed ferret (Mustela nigripes) as a case study for evaluating this
      emerging biomedical technology as a tool for genetic restoration. The black
      footed ferret has depleted genetic variation yet genome resource banks contain
      genetic material of individuals not currently represented in the extant lineage.
      Thus, genetic restoration of the species is in theory possible and could help
      reduce the persistent erosion of genetic diversity from drift. Extensive genetic,
      genomic, and reproductive science tools have previously been developed in black
      footed ferrets and would aid in the process of developing an iSCNT protocol for
      this species. Nonetheless, developing reproductive cloning will require years of
      experiments and a coordinated effort among recovery partners. The information
      gained from a well-planned research effort with the goal of genetic restoration
      via reproductive cloning could establish a 21st century model for evaluating and
      implementing conservation breeding that would be applicable to other genetically
      impoverished species. 

PMID- 26304985
TI  - Republished: Accuracy in interpreting the paediatric ECG: a UK-wide study and the
      need for improvement.
AB  - BACKGROUND: Paediatric ECG interpretation is significant for informed treatment
      of several conditions. Formal training in paediatric ECG is rarely undertaken.
      METHODS: A prospective survey based study module of UK-wide paediatricians
      registered with the UK Royal College of Paediatricians and Child Health (RCPCH)
      was conducted. 10 common clinical conditions seen in paediatrics for which there
      are recognisable ECGs had to be interpreted. After provision of an educational
      page, 10 further ECGs were presented. FINDINGS: 8450 RCPCH members were emailed a
      link to the online survey-study module, of whom 764 participated. Of these, 493
      interpreted the first 10 ECGs, and 385 interpreted both sets of ECGs. The
      accuracy for the first ECGs was 61.5% (63.5% for those who participated in the
      whole survey), and after use of the educational page increased to 73.3%. This was
      independent from previous ECG training. CONCLUSIONS: The use of an easily
      accessible online educational page improved the accuracy of paediatric ECG
      interpretation significantly. Internet based education can improve the accuracy
      of paediatric ECG interpretation and should be developed further.

PMID- 26304986
TI  - Republished: Respiratory microbiota: addressing clinical questions, informing
      clinical practice.
AB  - Over the last decade, technological advances have revolutionised efforts to
      understand the role played by microbes in airways disease. With the application
      of ever more sophisticated techniques, the literature has become increasingly
      inaccessible to the non-specialist reader, potentially hampering the translation
      of these gains into improvements in patient care. In this article, we set out the
      key principles underpinning microbiota research in respiratory contexts and
      provide practical guidance on how best such studies can be designed, executed and
      interpreted. We examine how an understanding of the respiratory microbiota both
      challenges fundamental assumptions and provides novel clinical insights into lung
      disease, and we set out a number of important targets for ongoing research. 

PMID- 26304987
TI  - Collaborative learning groups.

PMID- 26304988
TI  - Kupffer Cells Support Hepatitis B Virus-Mediated CD8+ T Cell Exhaustion via
      Hepatitis B Core Antigen-TLR2 Interactions in Mice.
AB  - Hepatitis B virus (HBV) persistence is a fundamental process in chronic HBV
      infection and a key factor in all related liver diseases; however, the mechanisms
      have yet to be elucidated. We studied the role of TLR2 in HBV persistence using a
      well-established HBV-carrier mouse model generated by hydrodynamically injecting
      a phospho-adeno-associated virus/HBV1.2 plasmid into mice. We found that a
      genetic deficiency in TLR2 improves HBV elimination, whereas activating TLR2 led
      to more stable HBV persistence, suggesting that TLR2 activation is critical in
      HBV persistence. Furthermore, we noted that TLR2 activation could inhibit CD8(+)
      T cell function, causing the exhaustion phenotype in HBV-carrier mice, because
      TLR2 deficiency might rescue CD8(+) T cell function in a cellular adoptive
      experiment. TLR2 expression on Kupffer cells (KCs) was upregulated in HBV-carrier
      mice, which accounts for HBV persistence, because the difference in anti-HBV
      immunity between HBV-carrier wild-type and Tlr2(-/-) mice did not exist after KC
      depletion. In addition, similar to TLR2 deficiency, after KC depletion, CD8(+) T
      cells were more efficiently activated in HBV-carrier mice, leading to rapid HBV
      elimination. KCs produced more IL-10 upon TLR2 activation in response to direct
      hepatitis B core Ag stimulation, and the elevated IL-10 inhibited CD8(+) T cell
      function in HBV-carrier mice, because IL-10 deficiency or anti-IL-10R treatment
      resulted in CD8(+) T cells with stronger antiviral function. In conclusion, KCs
      support liver tolerance by inducing anti-HBV CD8(+) T cell exhaustion via IL-10
      production after TLR2 activation by hepatitis B core Ag stimulation. 

PMID- 26304989
TI  - Interaction of Macrophage Antigen 1 and CD40 Ligand Leads to IL-12 Production and
      Resistance in CD40-Deficient Mice Infected with Leishmania major.
AB  - Although some studies indicate that the interaction of CD40 and CD40L is critical
      for IL-12 production and resistance to cutaneous leishmaniasis, others suggest
      that this pathway may be dispensable. In this article, we compared the outcome of
      Leishmania major infection in both CD40- and CD40L-deficient mice after treatment
      with rIL-12. We show that although CD40 and CD40L knockout (KO) mice are highly
      susceptible to L. major, treatment with rIL-12 during the first 2 wk of infection
      causes resolution of cutaneous lesions and control of parasite replication.
      Interestingly, although treated CD40 KO mice remained healed, developed long-term
      immunity, and were resistant to secondary L. major challenge, treated CD40L KO
      reactivated their lesion after cessation of rIL-12 treatment. Disease
      reactivation in CD40L KO mice was associated with impaired IL-12 and IFN-gamma
      production and a concomitant increase in IL-4 production by cells from lymph
      nodes draining the infection site. We show that IL-12 production by dendritic
      cells and macrophages via CD40L-macrophage Ag 1 (Mac-1) interaction is
      responsible for the sustained resistance in CD40 KO mice after cessation of rIL
      12 treatment. Blockade of CD40L-Mac-1 interaction with anti-Mac-1 mAb led to
      spontaneous disease reactivation in healed CD40 KO mice, which was associated
      with impaired IFN-gamma response and loss of infection-induced immunity after
      secondary L. major challenge. Collectively, our data reveal a novel role of CD40L
      Mac-1 interaction in IL-12 production, development, and maintenance of optimal
      Th1 immunity in mice infected with L. major. 

PMID- 26304990
TI  - Novel Noncompetitive IL-1 Receptor-Biased Ligand Prevents Infection- and
      Inflammation-Induced Preterm Birth.
AB  - Preterm birth (PTB) is firmly linked to inflammation regardless of the presence
      of infection. Proinflammatory cytokines, including IL-1beta, are produced in
      gestational tissues and can locally upregulate uterine activation proteins.
      Premature activation of the uterus by inflammation may lead to PTB, and IL-1 has
      been identified as a key inducer of this condition. However, all currently
      available IL-1 inhibitors are large molecules that exhibit competitive antagonism
      properties by inhibiting all IL-1R signaling, including transcription factor NF
      kappaB, which conveys important physiological roles. We hereby demonstrate the
      efficacy of a small noncompetitive (all-d peptide) IL-1R-biased ligand, termed
      rytvela (labeled 101.10) in delaying IL-1beta-, TLR2-, and TLR4-induced PTB in
      mice. The 101.10 acts without significant inhibition of NF-kappaB, and instead
      selectively inhibits IL-1R downstream stress-associated protein
      kinases/transcription factor c-jun and Rho GTPase/Rho-associated coiled-coil
      containing protein kinase signaling pathways. The 101.10 is effective at
      decreasing proinflammatory and/or prolabor genes in myometrium tissue and
      circulating leukocytes in all PTB models independently of NF-kappaB, undermining
      NF-kappaB role in preterm labor. In this work, biased signaling modulation of IL
      1R by 101.10 uncovers a novel strategy to prevent PTB without inhibiting NF
      kappaB. 

PMID- 26304991
TI  - PSTPIP2, a Protein Associated with Autoinflammatory Disease, Interacts with
      Inhibitory Enzymes SHIP1 and Csk.
AB  - Mutations in the adaptor protein PSTPIP2 are the cause of the autoinflammatory
      disease chronic multifocal osteomyelitis in mice. This disease closely resembles
      the human disorder chronic recurrent multifocal osteomyelitis, characterized by
      sterile inflammation of the bones and often associated with inflammation in other
      organs, such as the skin. The most critical process in the disease's development
      is the enhanced production of IL-1beta. This excessive IL-1beta is likely
      produced by neutrophils. In addition, the increased activity of macrophages,
      osteoclasts, and megakaryocytes has also been described. However, the molecular
      mechanism of how PSTPIP2 deficiency results in this phenotype is poorly
      understood. Part of the PSTPIP2 inhibitory function is mediated by protein
      tyrosine phosphatases from the proline-, glutamic acid-, serine- and threonine
      rich (PEST) family, which are known to interact with the central part of this
      protein, but other regions of PSTPIP2 not required for PEST-family phosphatase
      binding were also shown to be indispensable for PSTPIP2 function. In this
      article, we show that PSTPIP2 binds the inhibitory enzymes Csk and SHIP1. The
      interaction with SHIP1 is of particular importance because it binds to the
      critical tyrosine residues at the C terminus of PSTPIP2, which is known to be
      crucial for its PEST-phosphatase-independent inhibitory effects in different
      cellular systems. We demonstrate that in neutrophils this region is important for
      the PSTPIP2-mediated suppression of IL-1beta processing and that SHIP1 inhibition
      results in the enhancement of this processing. We also describe deregulated
      neutrophil response to multiple activators, including silica, Ab aggregates, and
      LPS, which is suggestive of a rather generalized hypersensitivity of these cells
      to various external stimulants. 

PMID- 26304992
TI  - Osteopontin Promotes Oncostatin M Production in Human Osteoblasts: Implication of
      Rheumatoid Arthritis Therapy.
AB  - Accumulating evidence indicates that subchondral bone might play an essential
      role in rheumatoid arthritis (RA). Osteopontin (OPN) induces the production of an
      important proinflammatory cytokine involved in the pathogenesis of RA. This study
      evaluated the activation of oncostatin M (OSM) by OPN in human primary
      osteoblasts to understand RA pathogenesis and characterized the intracellular
      signaling pathways involved in this activation. Quantitative PCR, ELISA, and
      Western blot results indicated that stimulation of human primary osteoblasts with
      OPN induces OSM expression through alphavbeta3 integrin/c-Src/platelet-derived
      growth factor receptor transactivation/MEK/ERK. Treatment of osteoblasts with OPN
      also increased c-Jun phosphorylation, AP-1 luciferase activity, and c-Jun binding
      to the AP-1 element on the OSM promoter, as demonstrated using chromatin
      immunoprecipitation assay. Moreover, inhibition of OPN expression using
      lentiviral-OPN short hairpin RNA resulted in the amelioration of articular
      swelling, cartilage erosion, and OSM expression in the ankle joint of mice with
      collagen-induced arthritis as shown using microcomputed tomography and
      immunohistochemistry staining. Our results imply that OSM expression in
      osteoblasts increases in response to OPN-induced inflammation in vitro. Finally,
      lentiviral-OPN short hairpin RNA ameliorates the inflammatory response and bone
      destruction in mice with collagen-induced arthritis. Therefore, OPN may be a
      potential therapeutic target for RA. 

PMID- 26304996
TI  - Micro-thermography in millimeter-scale animals by using orally-dosed fluorescent
      nanoparticle thermosensors.
AB  - We propose an instant micro-thermography method using a fluorescent-nanoparticle
      thermosensor capable of reporting temperature as the fluorescence intensity ratio
      of the temperature-sensitive dye to the reference. We demonstrate "temperature
      mapping" inside a fruit fly larva that was orally dosed with nanoparticle
      thermosensors. 

PMID- 26304997
TI  - A new strategy for site-specific alkylation of DNA using oligonucleotides
      containing an abasic site and alkylating probes.
AB  - Selective chemical reactions with DNA, such as its labelling, are very useful in
      many applications. In this paper, we discuss a new strategy for the selective
      alkylation of DNA using an oligonucleotide containing an abasic site and
      alkylating probes. We designed three probes consisting of 2-AVP as a reactive
      moiety and three kinds of binding moiety with high affinity to duplex DNA. Among
      these probes, Hoechst-AVP probe exhibited high selectivity and efficient
      reactivity to thymine bases at the site opposite an abasic site in DNA. Our
      method is potentially useful for inducing site-directed reactions aimed at
      inhibiting polymerase reactions. 

PMID- 26304998
TI  - Si-H activation by means of metal ligand cooperation in a methandiide derived
      carbene complex.
AB  - Si-H bond activation of a number of silanes via metal ligand cooperation in a
      carbene complex is reported. Thereby, the electronic flexibility of the carbene
      ligand allows for the activation via a unique mechanism with oxidative addition
      to an 18e species without a formal change in the number of valence electrons. 

PMID- 26304999
TI  - The chemical origin of the p-type and n-type doping effects in the hybrid
      methylammonium-lead iodide (MAPbI3) perovskite solar cells.
AB  - In the present Communication we discuss a field-induced and photoinduced self
      doping chemistry resulting in the formation of the positively and negatively
      charged vacancies in the MAPbI3 perovskite films. These vacancies induce p-type
      and n-type doping of the perovskite absorber leading to the realization of the p
      i-n device operation mechanism. 

PMID- 26305000
TI  - A hierarchically core/shell-structured titanosilicate with multiple mesopore
      systems for highly efficient epoxidation of alkenes.
AB  - A hierarchical titanosilicate, with epitaxially grown MFI nanosheets on
      microsized TS-1 crystals, has been prepared through a desilication
      recrystallization method using a diammonium surfactant as the secondary structure
      directing agent (SDA). This core/shell material features multiple mesoporosities,
      significantly improved epoxidation activity as well as easy separation in
      synthesis and catalytic reactions. 

PMID- 26305001
TI  - A thiol-thiosulfonate reaction providing a novel strategy for turn-on thiol
      sensing.
AB  - The first thiol-specific turn-on probe, BODIPY-TS, utilizing a thiosulfonate
      scaffold as the thiol recognition unit was reported. BODIPY-TS displays low
      toxicity, and features high sensitivity, fast response and quantitative reaction
      towards thiols. The structural novelty of BODIPY-TS would guide the development
      of novel thiol probes. 

PMID- 26305002
TI  - Reduced utility of serum IGF-1 levels in predicting retinopathy of prematurity
      reflects maternal ethnicity.
AB  - AIMS: To validate known risk factors and identify a threshold level for serum
      insulin-like growth factor 1 (IGF-1) in the development of severe retinopathy of
      prematurity (ROP) in an ethnically diverse population at a tertiary neonatal
      unit, 2011-2013. METHODS: A prospective cohort masked study was conducted. Serum
      IGF-1 levels at 31, 32 and 33 weeks were measured and risk factor data collected
      including gestational age (GA), birth weight (BW), absolute weight gain (AWG) and
      maternal ethnicity. The eventual ROP outcome was divided into two groups: minimal
      ROP (Stages 0 and 1) and severe ROP (Stage 2 or worse including Type 1 ROP).
      RESULTS: 36 patients were recruited: 14 had minimal ROP and 22 severe ROP.
      Significant differences between the groups were found in GA, BW, AWG and IGF-1 at
      32 and 33 weeks. There was minimal rise in IGF-1 in Stage 2 patients and/or black
      patients (p=0.0013) between 32 and 33 weeks but no pragmatic threshold level of
      IGF-1 that could distinguish between minimal or severe ROP. CONCLUSIONS: There
      were significant differences in GA, BW, AWG and IGF-1 at 32 and 33 weeks between
      those babies with severe ROP and those with minimal ROP. However, there was no
      threshold level of IGF-1 at a time point between 31 and 33 weeks that can be used
      to exclude a large proportion of babies from screening. We also found ethnic
      differences in IGF-1 levels with infants born to black mothers having
      significantly lower IGF-1 levels at 32 and 33 weeks gestation. The determination
      of ROP risk using IGF-1 is a race-specific phenomenon.

PMID- 26305003
TI  - Development of a new superficial punch for Descemet's Membrane Endothelial
      Keratoplasty donor tissue preparation.
AB  - Endothelial Keratoplasty (EK) is a corneal surgical procedure that allows a
      selective transplantation of the posterior layer of the cornea. Descemet's
      Membrane Endothelial Keratoplasty (DMEK) is one of the EK procedures in which the
      diseased Descemet's Membrane and the endothelium are replaced with a healthy
      donor tissue. To achieve this, the donor cornea is cut superficially from the
      endothelial side and the tissue can be separated using specific instruments like
      Pierse Notched, Acute or Fogla forceps. However, the pressure required to punch
      the superficial layer has always been a challenge and therefore a calibrated
      device to punch and excise the required superficial layer has been designed. This
      new model of punch will help to identify the peripheral edge of the DMEK
      lenticule which in turn helps to excise the tissue exclusively, further reducing
      the donor tissue wastage, as seen with the current tissue preparation methods. 

PMID- 26305005
TI  - CONCERN for Cancer: New National Institutes of Health Network to Focus on Cancer
      Patients in the Emergency Department.

PMID- 26305006
TI  - Abstracts for the 15th International Congress on Schizophrenia Research (ICOSR),
      March 28-April 1, 2015, Colorado Springs, Colorado.

PMID- 26305004
TI  - MRI does not add value over and above patient history and clinical examination in
      predicting time to return to sport after acute hamstring injuries: a prospective
      cohort of 180 male athletes.
AB  - BACKGROUND: MRI is frequently used in addition to clinical evaluation for
      predicting time to return to sport (RTS) after acute hamstring injury. However,
      the additional value of MRI to patient history taking and clinical examination
      remains unknown and is debated. AIM: To prospectively investigate the predictive
      value of patient history and clinical examination at baseline alone and the
      additional predictive value of MRI findings for time to RTS using multivariate
      analysis while controlling for treatment confounders. METHODS: Male athletes
      (N=180) with acute onset posterior thigh pain underwent standardised patient
      history, clinical and MRI examinations within 5 days, and time to RTS was
      registered. A general linear model was constructed to assess the associations
      between RTS and the potential baseline predictors. A manual backward stepwise
      technique was used to keep treatment variables fixed. RESULTS: In the first
      multiple regression model including only patient history and clinical
      examination, maximum pain score (visual analogue scale, VAS), forced to stop
      within 5 min, length of hamstring tenderness and painful resisted knee flexion
      (90 degrees ), showed independent associations with RTS and the final model
      explained 29% of the total variance in time to RTS. By adding MRI variables in
      the second multiple regression model, maximum pain score (VAS), forced to stop
      within 5 min, length of hamstring tenderness and overall radiological grading,
      showed independent associations and the adjusted R(2) increased from 0.290 to
      0.318. Thus, additional MRI explained 2.8% of the variance in RTS. SUMMARY: There
      was a wide variation in time to RTS and the additional predictive value of MRI
      was negligible compared with baseline patient history taking and clinical
      examinations alone. Thus, clinicians cannot provide an accurate time to RTS just
      after an acute hamstring injury. This study provides no rationale for routine MRI
      after acute hamstring injury. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov
      Identifier: NCT01812564.

PMID- 26305007
TI  - Abstracts of the XXXth Congress of the International Academy of Pathology,
      October 5, 2014, Bangkok, Thailand.

PMID- 26305008
TI  - Infectious Disease/CDC Update. Measles Outbreak - California, December 2014 -
      February 2015.

PMID- 26305009
TI  - Abstracts of the The 28th Annual North American Cystic Fibrosis Conference
      Georgia World Congress Center, October 9-11, 2014, Atlanta, Georgia.

PMID- 26305010
TI  - Abstracts of the European Biotechnology Congress 2014, May 15-18, 2014, Lecce,
      Italy.

PMID- 26305011
TI  - Summertime: A Chance for Rejuvenation, Change, and Transformation.

PMID- 26305013
TI  - THE VALUE OF AN HCV CURE. CURING HCV BENEFITS THE INDIVIDUAL--AND SOCIETY.

PMID- 26305012
TI  - THE COST OF LONG-TERM SURVIVAL. NEW FEARS EVOLVING WITH AGE.

PMID- 26305014
TI  - In vitro Cytotoxicity of Bisphenol A in  Monocytes Cell Line.
AB  - BACKGROUND/AIM: Bisphenol A (BPA) is used in the production of many plastics,
      which are used to build biomaterials that sometimes are in direct contact with
      blood. It is believed that the release of BPA into bloodstream may give rise to
      cytotoxic events for blood components. The aim of the present study was to
      perform an in vitro investigation of the observable cytotoxic effect of BPA, at
      increasing concentrations, on the monocyte cell line. METHODS: We incubated in
      vitro monocyte cells (U937) for 24 h in cell line medium samples (RPMI 1640) at
      different concentrations of BPA. We then generated curves to evaluate viability,
      necrosis and apoptosis of monocytes against increasing concentrations of BPA.
      RESULTS: The percentage values of concentrations of BPA corresponding to 50% of
      the viability and necrosis of the monocytes were 1.39 and 1.48 ng/ml,
      respectively. Based on our observations, we reported an increasing cytotoxic
      effect for higher concentrations. The apoptotic effect reached the maximum value
      at BPA concentration of 1.5 ng/ml; at still higher concentrations, we observed a
      predominantly necrotic cell death. CONCLUSION: Viability, necrosis and apoptosis
      of monocytes are strongly and positively correlated with BPA concentration. A
      direct contact of such compound with biological components of blood may lead to
      high levels of cytotoxicity, and require us to evaluate additional factors while
      judging the bio-incompatibility of BPA.

PMID- 26305015
TI  - Tuning of Ranvier node and internode properties in myelinated axons to adjust
      action potential timing.
AB  - Action potential timing is fundamental to information processing; however, its
      determinants are not fully understood. Here we report unexpected structural
      specializations in the Ranvier nodes and internodes of auditory brainstem axons
      involved in sound localization. Myelination properties deviated significantly
      from the traditionally assumed structure. Axons responding best to low-frequency
      sounds had a larger diameter than high-frequency axons but, surprisingly, shorter
      internodes. Simulations predicted that this geometry helps to adjust the
      conduction velocity and timing of action potentials within the circuit.
      Electrophysiological recordings in vitro and in vivo confirmed higher conduction
      velocities in low-frequency axons. Moreover, internode length decreased and
      Ranvier node diameter increased progressively along the distal axon segments,
      which simulations show was essential to ensure precisely timed depolarization of
      the giant calyx of Held presynaptic terminal. Thus, individual anatomical
      parameters of myelinated axons can be tuned to optimize pathways involved in
      temporal processing. 

PMID- 26305018
TI  - The development of category specificity in infancy--What can we learn from
      electrophysiology?
AB  - In this review I address the question why relatively little is currently known
      about the neural bases of category learning and beginning category identification
      in infancy. Electrophysiological research on infants' basic-level and global
      level categorization has mainly focused on general measures of visual attention,
      not on specific neural processes underlying the development and identification of
      visual categories. Our knowledge on categorization processes in the infant brain
      is mainly limited to faces as categories. I will call for the use of EEG-based
      techniques such as rapid repetition ERP paradigms and fast periodic stimulation
      that have only rarely been used with infants in order to gain a better
      understanding of the development of category representations in the infant brain.

PMID- 26305016
TI  - Microsecond Simulations of the Diphtheria Toxin Translocation Domain in
      Association with Anionic Lipid Bilayers.
AB  - Diphtheria toxin translocation (T) domain undergoes conformational changes in
      acidic solution and associates with the lipid membranes, followed by refolding
      and transmembrane insertion of two nonpolar helices. This process is an essential
      step in delivery of the toxic catalytic domain of the diphtheria toxin to the
      infected cell, yet its molecular determinants are poorly characterized and
      understood. Therefore, an atomistic model of the T-domain-membrane interaction is
      needed to help characterize factors responsible for such association. In this
      work, we present atomistic model structures of T-domain membrane-bound
      conformations and investigate structural factors responsible for T-domain
      affinity with the lipid bilayer in acidic solution using all-atom molecular
      dynamics (MD) simulations. The initial models of the protein conformations and
      protein-membrane association that serve as starting points in the present work
      were developed using atomistic simulations of partial unfolding of the T-domain
      in acidic solution (Kurnikov, I. V.; et al. J. Mol. Biol. 2013, 425, 2752-2764),
      and coarse-grained simulations of the T-domain association with the membranes of
      various compositions (Flores-Canales, J. C.; et al. J. Membr. Biol. 2015, 248,
      529-543). In this work we present atomistic level modeling of two distinct
      configurations of the T-domain in association with the anionic lipid bilayer. In
      microsecond-long MD simulations both conformations retain their compact structure
      and gradually penetrate deeper into the bilayer interface. One membrane-bound
      conformation is stabilized by the protein contacts with the lipid hydrophobic
      core. The second modeled conformation is initially inserted less deeply and forms
      multiple contacts with the lipid at the interface (headgroup) region. Such
      contacts are formed by the charged and hydrophilic groups of partially unfolded
      terminal helixes and loops. Neutralization of the acidic residues at the membrane
      interface allows for deeper insertion of the protein and reorientation of the
      protein at the membrane interface, which corroborates that acidic residue
      protonation as well as presence of the anionic lipids may play a role in the
      membrane association and further membrane insertion of the T-domain as implicated
      in experiments. All simulations reported in this work were performed using AMBER
      force-field on Anton supercomputer. To perform these reported simulations, we
      developed and carefully tested a force-field for the anionic 1-palmitoyl-2-oleoyl
      phosphatidyl-glycerol (POPG) lipid, compatible with the Amber 99SB force-field
      and stable in microsecond-long MD simulations in isothermal-isobaric ensemble. 

PMID- 26305017
TI  - Different Effects of Ranibizumab and Bevacizumab on Platelet Activation Profile.
AB  - PURPOSE: The aim of the study was to evaluate the potential influence of
      ranibizumab and bevacizumab on platelet activation and aggregation, which are
      critical processes in the pathogenesis of arterial thromboembolic events (ATEs).
      METHODS: For the assessment of platelet function, flow cytometry and aggregometry
      were employed. Platelets were isolated from healthy volunteers and exposed to
      ranibizumab (1 mg/ml and 150 ng/ml) and bevacizumab (2.5 mg/ml and 3 MUg/ml) or
      their solvents for 10 and 30 min prior to the addition of TRAP (25 MUM), PAR-4-AP
      (25 MUM) or thrombin (0.02 U/ml). The surface expression of activated GP
      IIb/IIIa, P-selectin (CD62P) and platelet-bound stromal cell-derived factor-1
      (SDF-1) was measured on resting (nonactivated) and activated platelets by flow
      cytometry. The platelet aggregation capacity was examined using light
      transmission aggregometry. RESULTS: The expression of surface activation markers
      did not differ significantly between nonstimulated and TRAP-, PAR-4-AP- or
      thrombin-activated platelets after incubating with ranibizumab. However, GP
      IIb/IIIa, CD62P and SDF-1 were significantly downregulated in PAR-4-AP- and
      thrombin-activated platelets after exposure to bevacizumab 2.5 mg/ml. In
      addition, ranibizumab- and bevacizumab-FITC were significantly increased in all
      activated platelets. No significant differences were observed in the aggregation
      of activated platelets after incubation with ranibizumab or bevacizumab.
      CONCLUSION: All ranibizumab concentrations as well as the bevacizumab
      concentration of 3 MUg/ml had no influence on platelet activation and
      aggregation. Therefore, this in vitro study did not show any relationship between
      the exposition of activated platelets to ranibizumab or bevacizumab and the
      development of ATEs. However, the highest level of bevacizumab interfered with
      platelet activation, leading to downregulation of platelet activation markers.
      This observation might explain why the systemic treatment with high-dose
      bevacizumab could be associated with an increased risk of bleeding. Regarding the
      use of lower intravitreal dosages, further research should focus on the complex
      interactions between platelets and other cells, such as endothelial cells, which
      might stronger relate to a potentially increased risk of ATEs and depend on
      systemic vascular endothelial growth factor levels. Facing the different
      activation profiles, the diverse effects of the drugs on the cellular level have
      to be critically scrutinized for their clinical relevance.

PMID- 26305019
TI  - Thermal dimerization of [n]cumulenes (n = 5, 7, 9).
AB  - The thermal dimerization of three [n]cumulenes (n = 5, 7, and 9) has been
      investigated, and a common reactivity pattern is observed that gives radialenes
      and expanded radialenes through regioselective cycloaddition reactions; all three
      products are characterized using X-ray crystallography. 

PMID- 26305022
TI  - [Endobronchial ultrasound transbronchial needle aspiration initiation into the
      Lyon Sud hospital center: Experience of the first three years].
AB  - INTRODUCTION: Endobronchial ultrasound is a recent technique for the diagnosis
      and the lymph node staging in lung cancer. It also showed interest in non tumoral
      mediastinal lymph nodes diagnosis. This work relates the CHLS first three years'
      experience in terms of EEB practical use as a new diagnostic tool in this field.
      METHODS: Retrospective study of consecutive cases patients having undergone
      endobronchial ultrasound from November 2008 till June 2011 in the CHLS. RESULTS:
      On 65 endobronchial ultrasound, general anesthesia was practiced in 89 % of the
      cases, with a good tolerance in 81 % of the cases. In 77 % cases, EEB allowed
      diagnosis and avoided mediastinoscopy in 60.5 % of the cases. The respective
      sensibility, specificity, positive and negative predictive values were 74 %, 100
      %, 100 % and 48 %. CONCLUSION: These data, reflect of a novice team experience,
      illustrate the results obtained in the current practice in terms of etiologic
      diagnosis. Endobronchial ultrasound seems destined to a bright future but
      requires the development of dedicated centers allowing pulmonologists training
      and specialized pathologists in this field.

PMID- 26305021
TI  - Cost-effectiveness analysis of levobupivacaine 0.5 %, a local anesthetic,
      infusion in the surgical wound after modified radical mastectomy.
AB  - BACKGROUND AND OBJECTIVE: Effective treatment of postoperative pain contributes
      to decreasing the rate of complications as well as the total cost of the operated
      patients. The aim of this study was to analyze the costs and the efficiency of
      use of continuous infusion of levobupivacaine 0.5 % with the help of an infusion
      pump in modified radical mastectomy. METHODS: A cost calculation of the analgesic
      procedures (continuous infusion of levobupivacaine 0.5 % [levobupivacaine group
      (LG)] or saline [saline group (SG)] (2 ml/h 48 h) has been carried out based on
      the data of a previous clinical trial (double-blind randomized study) of patients
      who underwent modified radical mastectomy surgery. The measure of the
      effectiveness was the point reduction of pain derived from the verbal numeric
      rating scale (VNRS). The usual incremental cost-effectiveness ratio (ICER) was
      performed. RESULTS: Considering only the intravenous analgesia, overall costs
      were lower in LG, as less analgesia was used (EUR14.06 +/- 7.89 vs. 27.47 +/-
      14.79; p < 0.001). In this study the costs of the infusion pump were not
      calculated as it was used by both groups and they offset each other. However, if
      the infusion pump costs were included, costs would be higher in the LG, (EUR91.89
      +/- 7.89 vs. 27.47 +/- 14.79; p < 0.001) and then the ICER was -8.51, meaning
      that for every extra point of decrease in the pain verbal numerical rating score
      over the 2-day period, the cost increased by EUR8.51. CONCLUSION: Infiltration of
      local anesthetics is an effective technique for controlling postoperative pain
      and the associated added costs are relatively low in relation to the total cost
      of mastectomy, therefore providing patients with a higher quality of care in the
      prevention of pain. CLINICAL TRIALS REGISTRATION: clinicaltrials.gov: reference
      number NCT01389934. http://clinicaltrials.gov/show/NCT01389934

PMID- 26305023
TI  - Prognostic Impact of Visceral Fat Amount and Branched-Chain Amino Acids (BCAA) in
      Hepatocellular Carcinoma.
AB  - BACKGROUND: Dysregulation of lipid and amino acid metabolism in patients with
      liver diseases results in obesity-related carcinogenesis and decreased levels of
      branched-chain amino acids (BCAA), respectively. This study assessed the clinical
      and prognostic impact of visceral fat amount (VFA) and its association with amino
      acid metabolism in patients with hepatocellular carcinoma (HCC). METHODS: In this
      study, 215 patients who underwent hepatic resection for HCC were divided into two
      groups based on VFA criteria for metabolic abnormalities in Japan. Computed
      tomography was used to measure VFA at the third lumbar vertebra in the inferior
      direction. RESULTS: Of the 215 patients, 132 had high and 83 had low VFA. High
      VFA was significantly associated with older age and higher body mass index (BMI),
      subcutaneous fat amount, and BCAA, but not with liver function, nutrient status,
      or tumoral factors. VFA was positively correlated with BMI (P < 0.0001; r = 0.63)
      and BCAA levels (P < 0.0001; r = 0.29). Overall survival was significantly
      greater in the high than in the low VFA group (P = 0.002). Multivariate analyses
      showed that high VFA [hazard ratio (HR) 7.06; P = 0.024] and
      neutrophil/lymphocyte ratio (HR 3.47; P = 0.049) were significantly prognostic of
      overall survival, whereas subcutaneous fat amount, BMI, BCAA, serum albumin, and
      prognostic nutritional index were not. CONCLUSIONS: High VFA was associated with
      a high BCAA level, with high VFA prognostic of improved overall survival in
      Japanese patients with HCC.

PMID- 26305024
TI  - Managing Endometrial Cancer: The Role of Pelvic Lymphadenectomy and Secondary
      Surgery.
AB  - PURPOSE: In November 2010, the French National Cancer Institute published new
      guidelines for managing endometrial cancer. Pelvic lymphadenectomy is not
      indicated for preoperative low-intermediate risk type 1 endometrial cancer, and
      high-risk patients should undergo secondary surgery with para-aortic
      lymphadenectomy. This study evaluated these new guidelines with regard to overall
      survival (OS), relapse-free survival (RFS), and morbidity for patients with low
      intermediate risk disease. METHODS: We evaluated all type 1 endometrial cancer
      patients with low-intermediate risk of recurrence who were treated from 1 January
      1997 through 31 December 2012. All patients were classified according to the 2009
      International Federation of Gynecology and Obstetrics staging criteria and the
      European Society for Medical Oncology. RESULTS: Overall, 230 patients were
      included (159 before and 71 after the new guidelines were issued). Pelvic
      lymphadenectomies were performed before and after the new guidelines in 77.4 and
      28.6 % of patients, respectively (p < 0.001). After 2010, eight patients also
      underwent secondary surgery, which consisted of a para-aortic lymphadenectomy for
      lymphovascular space invasion (LVSI). This second surgery changed the adjuvant
      treatment for one patient. OS and RFS were similar between both groups, and no
      difference in morbidity was observed between the groups. LVSI was an independent
      factor for OS [hazard ratio (HR) 7.2, 95 % CI 3.1-17; p < 0.001] and RFS (HR 3.7,
      95 % CI 1.6-8.5; p < 0.003). CONCLUSIONS: Fewer pelvic lymphadenectomies in low
      intermediate risk patients did not affect OS, RFS, or morbidity, including
      patients with secondary surgery. We must gather additional data with a longer
      follow-up period to not only confirm our results but to also fully investigate
      the paradoxical absence of decreased morbidity that our study has shown.

PMID- 26305020
TI  - Histone methylation modifiers in cellular signaling pathways.
AB  - Histone methyltransferases and demethylases epigenetically regulate gene
      expression by modifying histone methylation status in numerous cellular
      processes, including cell differentiation and proliferation. These modifiers also
      control methylation levels of various non-histone proteins, such as effector
      proteins that play critical roles in cellular signaling networks. Dysregulated
      histone methylation modifiers alter expression of oncogenes and tumor suppressor
      genes and change methylation states of effector proteins, frequently resulting in
      aberrant cellular signaling cascades and cellular transformation. In this review,
      we summarize the role of histone methylation modifiers in regulating the
      following signaling pathways: NF-kappaB, RAS/RAF/MEK/MAPK, PI3K/Akt, Wnt/beta
      catenin, p53, and ERalpha. 

PMID- 26305025
TI  - Comparative Outcomes of Neoadjuvant Treatment Prior to Total Mesorectal Excision
      and Total Mesorectal Excision Alone in Selected Stage II/III Low and Mid Rectal
      Cancer.
AB  - BACKGROUND: Current guidelines advocate that all rectal cancer patients with
      American Joint Committee on Cancer (AJCC) stages II and III disease should be
      subjected to neoadjuvant therapy. However, improvements in surgical technique
      have resulted in single-digit local recurrence rates with surgery only. METHODS:
      Operative, postoperative, and oncological outcomes of patients with and without
      neoadjuvant therapy were compared between January 2002 and December 2013. For
      this purpose, all patients resected with low anterior rectal resection (LAR) and
      total mesorectal excision (TME) who had or had not been irradiated were
      identified from the authors' prospectively maintained database. Patients who were
      excluded were those with high rectal cancer or AJCC stage IV disease; in the
      surgery-only group, patients with AJCC stage I disease or with pT4Nx rectal
      cancer; and in the irradiated patients, patients with ypT4Nx or cT4Nx rectal
      cancer. RESULTS: Overall, 454 consecutive patients were included. A total of 342
      (75 %) patients were irradiated and 112 (25 %) were not irradiated. Median follow
      up for all patients was 48 months. Among patients with and without irradiation,
      pathological circumferential resection margin positivity rates (2.9 vs. 1.8 %, p
      = 0.5) were not different. At 5 years, in irradiated patients compared with
      surgery-only patients, the incidence of local recurrence was decreased (4.5 vs.
      3.8 %, p = 0.5); however, systemic recurrences occurred more frequently (10 vs.
      17.8 %, p = 0.2). Irradiation did not affect overall or disease-free survival
      (neoadjuvant treatment vs. surgery-only: 84.9 vs. 88.2 %, p = 0.9; 76 vs. 79.1 %,
      p = 0.8). CONCLUSIONS: The current study adds to the growing evidence that
      suggests a selective rather than generalized indication for neoadjuvant treatment
      in stages II and III rectal cancer.

PMID- 26305026
TI  - Serum miR-335 Level is Associated with the Treatment Response to Trans-Arterial
      Chemoembolization and Prognosis in Patients with Hepatocellular Carcinoma.
AB  - AIM: To identify the role of serum MicroRNA-335 (miR-335) in determining the
      treatment response to Trans-arterial chemoembolization (TACE) in patients with
      hepatocellular carcinoma (HCC) and their prognosis after TACE. METHODS: A total
      of 125 HCC patients were enrolled in this study. All these patients underwent
      TACE and the treatment response was evaluated. All patients were followed for
      prognosis analyses. Serum miR-335 levels immediate before and 30 days after TACE
      were determined. RESULTS: HCC patients had significantly lower miR-335 levels
      than hepatitis patients and healthy controls. Lower serum miR-335 levels were
      closely associated with more progressive clinical features, including a higher
      mean serum AFP level, more vascular invasion, cirrhosis and larger tumor size.
      Response rates were higher in patients with high miR-335 compared to those with
      low miR-335 level. Patients with lower serum miR-335 levels had significantly
      poorer prognosis than patients with higher serum miR-335 levels. CONCLUSION: Our
      data suggest that serum miR-335 can be used as a molecular marker to predict the
      treatment response and clinical outcome in HCC patients receiving TACE.

PMID- 26305028
TI  - STORY AND HISTORY IN FETAL BEHAVIOR RESEARCH.
AB  - In their monograph, DiPietro, Costigan, and Voegtline present an important and
      thoughtful portrait of low-risk fetal development during the last trimester of
      gestation, and they also pay tribute to the Fels Longitudinal Study
      investigators' early work in this area. In this commentary, the history and
      legacy of the Fels Institute is further explored within the broader context of
      fetal research, and DiPietro et al.'s findings are placed in alignment with
      contemporary dynamic systems' theoretical approaches that emphasize longitudinal
      analysis of emergent behavior and process during early development. The
      commentary puts forth the assertion that the work reported by DiPietro and her
      colleagues tells a story that sets the stage for a new generation of technology
      enhanced and culturally expanded investigations of fetal behavior. 

PMID- 26305029
TI  - Endometrial polyps: when to resect?
AB  - PURPOSE: To determine the prevalence of malignant and premalignant endometrial
      polyps and to investigate the association of malignancy with specific factors.
      METHODS: This is a retrospective study of women submitted to hysteroscopic
      resection of endometrial polyps between January 2005 and July 2013 at a
      university hospital in southern Brazil. Data regarding clinical characteristics
      and pathology findings were collected from patient charts. RESULTS: Of 359
      patients, 87.2% had benign polyps and 9.9% had hyperplasia without atypia.
      Atypical hyperplasia was found in 2.6% of the sample. Endometrial adenocarcinoma
      was found in one woman (0.3%). A correlation was observed between
      malignant/premalignant polyps and patient age, menopausal status, and uterine
      bleeding. All patients with malignancies/premalignancies had abnormal uterine
      bleeding. Higher frequency of malignant polyps was observed in tamoxifen users,
      however, without statistical significance (p = 0.059%). Malignancy was not
      correlated with arterial hypertension, diabetes mellitus, obesity, hormone
      therapy, endometrial thickness, and polyp diameter. CONCLUSIONS:
      Malignant/premalignant findings had low prevalence and were absent in
      asymptomatic patients. From the data of this retrospective study, it is unclear
      whether routine polypectomy should be performed in asymptomatic patients. Further
      prospective studies including larger numbers of patients are required to guide
      treatment recommendations.

PMID- 26305030
TI  - Predictive model for risk of cesarean section in pregnant women after induction
      of labor.
AB  - PURPOSE: To develop a predictive model for risk of cesarean section in pregnant
      women after induction of labor. METHODS: A retrospective cohort study was
      conducted of 861 induced labors during 2009, 2010, and 2011 at Hospital "La
      Mancha-Centro" in Alcazar de San Juan, Spain. Multivariate analysis was used with
      binary logistic regression and areas under the ROC curves to determine predictive
      ability. Two predictive models were created: model A predicts the outcome at the
      time the woman is admitted to the hospital (before the decision to of the method
      of induction); and model B predicts the outcome at the time the woman is
      definitely admitted to the labor room. RESULTS: The predictive factors in the
      final model were: maternal height, body mass index, nulliparity, Bishop score,
      gestational age, macrosomia, gender of fetus, and the gynecologist's overall
      cesarean section rate. The predictive ability of model A was 0.77 [95% confidence
      interval (CI) 0.73-0.80] and model B was 0.79 (95% CI 0.76-0.83). The predictive
      ability for pregnant women with previous cesarean section with model A was 0.79
      (95% CI 0.64-0.94) and with model B was 0.80 (95% CI 0.64-0.96). For a
      probability of estimated cesarean section >=80%, the models A and B presented a
      positive likelihood ratio (+LR) for cesarean section of 22 and 20, respectively.
      Also, for a likelihood of estimated cesarean section <=10%, the models A and B
      presented a +LR for vaginal delivery of 13 and 6, respectively. CONCLUSION: These
      predictive models have a good discriminative ability, both overall and for all
      subgroups studied. This tool can be useful in clinical practice, especially for
      pregnant women with previous cesarean section and diabetes.

PMID- 26305031
TI  - Obstetrical prognosis of patients with cervical intraepithelial neoplasia (CIN)
      after "coin-shaped" conization.
AB  - PURPOSE: Uterine cervical conization is related to adverse pregnancy outcomes in
      subsequent pregnancies. To deal with this problem, we started conservative coin
      shaped conization for reproductive-aged patients with cervical intraepithelial
      neoplasia (CIN). Here we report both the obstetrical and oncological impacts of
      this operation in comparison with the standard cone-shaped resection. METHODS: A
      total of 401 women 44 years old or younger were treated in our hospital by CO2
      laser conization between 2003 and 2012, and subsequently 50 patients became
      pregnant. The patients were divided into two groups, a standard cone-shaped
      conization group (until 2008) and a shallow coin-shaped conization group
      (beginning in 2008). The pregnancy courses and oncological prognoses of these two
      groups were studied. RESULTS: Cone height reduction of about 3 mm was done.
      However, there were no significant differences between the two groups with regard
      to the occurrence of oncological complications. In the standard conization group,
      18 of the 25 patients delivered at term. In the coin-shaped conization group, 20
      of the 25 patients delivered at term. There were no significant differences
      between the two groups with regard to the occurrence of various obstetrical
      complications. However, the reduction rate of cervical length over the pregnancy
      was smaller in the coin-shaped group and the number of patients with a short
      cervix length of 2 cm or less was smaller in the coin-shaped group. CONCLUSIONS:
      Although conservative coin-shaped conization did not markedly improve the
      obstetrical prognosis, this operative procedure improved the reduction rate of
      uterine cervical length over the pregnancy without any increase in oncological
      complications.

PMID- 26305032
TI  - Clinical impact of high mobility group box 1 protein in epithelial ovarian
      cancer.
AB  - PURPOSE: The aim of this study was to confirm the expression of high mobility
      group box 1 (HMGB1) in patients with epithelial ovarian cancer (EOC) and to
      evaluate the prognostic significance of HMGB1. METHODS: A total of 74 patients
      with EOC comprised our cohort. Retrospectively collected tissue microarray from
      EOC patients treated with debulking surgery followed by taxane and platinum
      chemotherapy were analyzed for evaluation of the prognostic significance of
      HMGB1. Expression of HMGB1 was assessed by immunohistochemistry. RESULTS: The
      positive staining was detected in 80% of EOC patients and the rate of high HMGB1
      expression was 42%. In advanced stage, patients with high HMGB1 expression showed
      a poorer prognosis than low HMGB1 expression group [median progression-free
      survival (PFS), 10.8 vs. 21.7 months, P = 0.005]. High HMGB1 expression was an
      independent predictor for PFS (P = 0.024). CONCLUSIONS: HMGB1 expression is
      expected as a promising biomarker for EOC and further studies are needed to
      assess potential roles in EOC.

PMID- 26305033
TI  - Clinical usefulness of the oral chemotherapy agent S-1 in heavily pre-treated
      patients with advanced or recurrent cervical cancer.
AB  - PURPOSE: Our aim was to evaluate the efficacy and safety of S-1 in heavily pre
      treated patients with advanced (FIGO stage IVB) or recurrent cervical cancer.
      METHODS: The Institutional Review Board of our hospital approved the protocol for
      this retrospective phase II study. Patients with measurable disease received two
      oral doses of S-1 (35 mg/m(2)) daily for 4 weeks of a 6-week cycle or 2 weeks of
      a 3-week cycle. The antitumor effect, time to progression, overall survival, and
      adverse events were investigated. RESULTS: We retrospectively analyzed relevant
      data of 28 patients with advanced or recurrent cervical cancer. Twenty-two
      patients had prior chemotherapy (not including chemoradiotherapy) and 27 had
      prior radiotherapy. The median number of prior chemotherapy regimens and cycles
      was 2 (range 0-4) and 7 (range 0-35), respectively. Two patients (7.1%) had
      partial response, and 10 patients (35.7%) had stable disease. Ten patients
      (35.7%) discontinued the therapy because of progressive disease. The response in
      5 patients could not be evaluated because of termination of treatment in the
      middle of the first cycle. The disease control rate was 42.8%. After a median
      follow-up duration of 7.5 months, the median time to progression was 4.2 months
      (95% CI 2.7-5.4) and the median overall survival was 9.92 months (95% CI 9.20
      NA). The two patients with partial response had received less prior chemotherapy.
      CONCLUSIONS: Oral S-1 in palliative chemotherapy is a useful and well-tolerated
      treatment in heavily pre-treated patients with advanced or recurrent uterine
      cervical cancer.

PMID- 26305034
TI  - Prostate cancer: Docetaxel plus ADT significantly improves patient outcomes.

PMID- 26305036
TI  - Chemotherapy: Rolapitant-a new and safer antiemetic agent.

PMID- 26305037
TI  - Haematological cancer: Resiquimod-a topical CTCL therapy.

PMID- 26305038
TI  - New cassettes for single-step drug resistance and prototrophic marker switching
      in fission yeast.
AB  - Construction of multiply mutated strains for genetic interaction analysis and of
      strains carrying different epitope tags at multiple open reading frames for
      testing protein localization, abundance and protein-protein interactions is
      hampered by the availability of a sufficient number of different selectable
      markers. Moreover, strains with single gene deletions or tags often already exist
      in strain collections; for historical reasons these will mostly carry the ura4(+)
      gene or the G418-resistance kanMX as marker. Because it is rather cumbersome to
      produce multiply deleted or tagged strains using the same marker, or to
      completely reconstruct a particular strain with a different marker, single-step
      exchange protocols of markers are a time-saving alternative. In recent years,
      dominant drug resistance markers (DDRMs) against clonNAT, hygromycin B and
      bleomycin have been adapted and successfully used in Schizosaccharomyces pombe.
      The corresponding DDRM cassettes, natMX, hphMX and bleMX, carry the TEF promotor
      and terminator sequences from Ashbya gossypii as kanMX; this provides flanking
      homologies to enable single-step marker swapping by homologous gene targeting. To
      expand this very useful toolset for single-step marker exchange, I constructed MX
      cassettes containing the nutritional markers arg3(+), his3(+), leu1(+) and
      ura4(+). Furthermore, a set of constructs was created to enable single-step
      exchange of ura4(+) to kanMX6, natMX4 and hphMX4. The functionality of the
      cassettes is demonstrated by successful single-step marker swapping at several
      loci. These constructs allow straightforward and rapid remarking of existing
      ura4(+) - and MX-deleted and -tagged strains.

PMID- 26305035
TI  - Modern approaches to HLA-haploidentical blood or marrow transplantation.
AB  - Allogeneic blood or bone-marrow transplantation (alloBMT) is a potentially
      curative treatment for a variety of haematological malignancies and nonmalignant
      diseases. Historically, human leukocyte antigen (HLA)-matched siblings have been
      the preferred source of donor cells owing to superior outcomes compared with
      alloBMT using other donors. Although only approximately one-third of patients
      have an HLA-matched sibling, nearly all patients have HLA-haploidentical related
      donors. Early studies using HLA-haploidentical alloBMT resulted in unacceptably
      high rates of graft rejection and graft-versus-host disease (GVHD), leading to
      high nonrelapse mortality and consequently poor survival. Several novel
      approaches to HLA-haploidentical alloBMT have yielded encouraging results with
      high rates of successful engraftment, effective GVHD control and favourable
      outcomes. In fact, outcomes of several retrospective comparative studies seem
      similar to those seen using other allograft sources, including those of HLA
      matched-sibling alloBMT. In this Review, we provide an overview of the three most
      developed approaches to HLA-haploidentical alloBMT: T-cell depletion with
      'megadose' CD34(+) cells; granulocyte colony-stimulating factor-primed allografts
      combined with intensive pharmacological immunosuppression, including
      antithymocyte globulin; and high-dose, post-transplantation cyclophosphamide. We
      review the preclinical and biological data supporting each approach, results from
      major clinical studies, and completed or ongoing clinical studies comparing these
      approaches with other alloBMT platforms. 

PMID- 26305039
TI  - Psychological Stress-Derived Prolactin Modulates Occludin Expression in Vaginal
      Epithelial Cells to Compromise Barrier Function.
AB  - BACKGROUND/AIMS: The causative factors of the vaginitis are not fully understood
      yet. Epithelial barrier dysfunction plays a critical role in the pathogenesis of
      vaginitis. This study aims to investigate the role of prolactin (PRL) in the
      causing the vaginal epithelial barrier dysfunction. METHODS: Adult rats were
      treated with water-avoid-stress. The serum levels of PRL were determined by
      ELISA. T84 cell (T84 cells; a vaginal epithelial cell line) monolayers were
      prepared to be used assessing the epithelial barrier functions. The expression of
      occludin in T84 cells was assessed by Chromatin immunoprecipitation assay,
      methylation specifIc PCR, real time quantitative RT-PCR and Western blotting.
      RESULTS: The results showed that psychological stress markedly increased the
      serum levels of PRL in the rat vaginal epithelia. Exposure of T84 cells to PRL in
      the culture markedly increased the phosphorylation of STAT3 and suppressed the
      expression of occludin in the cells; the transepithelial electric resistance was
      decreased and the permeability to a macromolecular tracer was increased in the
      T84 monolayers, which was mimicked by blocking STAT3, or abolished by over
      expression of occludin in the epithelial cells. CONCLUSIONS: Psychological stress
      derived PRL induces vaginal epithelial barrier dysfunction by inhibiting the
      expression of occludin.

PMID- 26305040
TI  - New vectors for simple and streamlined CRISPR-Cas9 genome editing in
      Saccharomyces cerevisiae.
AB  - Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9
      technology is an important tool for genome editing because the Cas9 endonuclease
      can induce targeted DNA double-strand breaks. Targeting of the DNA break is
      typically controlled by a single-guide RNA (sgRNA), a chimeric RNA containing a
      structural segment important for Cas9 binding and a 20mer guide sequence that
      hybridizes to the genomic DNA target. Previous studies have demonstrated that
      CRISPR-Cas9 technology can be used for efficient, marker-free genome editing in
      Saccharomyces cerevisiae. However, introducing the 20mer guide sequence into
      yeast sgRNA expression vectors often requires cloning procedures that are
      complex, time-consuming and/or expensive. To simplify this process, we have
      developed a new sgRNA expression cassette with internal restriction enzyme sites
      that permit rapid, directional cloning of 20mer guide sequences. Here we describe
      a flexible set of vectors based on this design for cloning and expressing sgRNAs
      (and Cas9) in yeast using different selectable markers. We anticipate that the
      Cas9-sgRNA expression vector with the URA3 selectable marker (pML104) will be
      particularly useful for genome editing in yeast, since the Cas9 machinery can be
      easily removed by counter-selection using 5-fluoro-orotic acid (5-FOA) following
      successful genome editing. The availability of new vectors that simplify and
      streamline the technical steps required for guide sequence cloning should help
      accelerate the use of CRISPR-Cas9 technology in yeast genome editing.

PMID- 26305042
TI  - Alcohol consumption is higher among left-behind Chinese children whose parents
      leave rural areas to work.
AB  - AIM: Over the past few decades, a large number of rural residents have migrated
      to cities in China and left their children behind. This study estimated how many
      10- to 14-year-old children in rural Anhui drank alcohol and examined the
      association between parental migration and children's alcohol use. METHODS: A
      cross-sectional study was conducted in six cities in Anhui between July and
      August 2012. All participants had lived in the study villages for at least six
      months during the previous year and were interviewed face-to-face using a
      standardised questionnaire. RESULTS: More than half (57%) of the 1367 subjects
      were left-behind children, 43% lived with both parents and 9.6% currently drank
      alcohol. When we controlled for other variables, the rate of alcohol use was
      statistically higher among left-behind children if both parents had migrated
      (14.0%) than among children living with both parents (7.8%) (p = 0.002). Boys,
      children with siblings and those with a poorer academic performance were more
      likely to drink. CONCLUSION: Children in rural China were more likely to drink if
      both their parents had migrated in search of work. School-based interventions
      could help to reduce alcohol use among rural left-behind children, especially
      boys.

PMID- 26305041
TI  - Glucocorticoids improve erythroid progenitor maintenance and dampen Trp53
      response in a mouse model of Diamond-Blackfan anaemia.
AB  - Diamond-Blackfan anaemia (DBA) is a rare congenital disease causing severe
      anaemia and progressive bone marrow failure. The majority of patients carry
      mutations in ribosomal proteins, which leads to depletion of erythroid
      progenitors in the bone marrow. As many as 40% of all DBA patients receive
      glucocorticoids to alleviate their anaemia. However, despite their use in DBA
      treatment for more than half a century, the therapeutic mechanisms of
      glucocorticoids remain largely unknown. Therefore we sought to study disease
      specific effects of glucocorticoid treatment using a ribosomal protein s19
      (Rps19) deficient mouse model of DBA. This study determines for the first time
      that a mouse model of DBA can respond to glucocorticoid treatment, similar to DBA
      patients. Our results demonstrate that glucocorticoid treatment reduces
      apoptosis, rescues erythroid progenitor depletion and premature differentiation
      of erythroid cells. Furthermore, glucocorticoids prevent Trp53 activation in
      Rps19-deficient cells- in a disease-specific manner. Dissecting the therapeutic
      mechanisms behind glucocorticoid treatment of DBA provides indispensible insight
      into DBA pathogenesis. Identifying mechanisms important for DBA treatment also
      enables development of more disease-specific treatments of DBA. 

PMID- 26305043
TI  - Eptifibatide-induced thrombocytopenia leading to acute stent thrombosis.
AB  - A 71-year old female patient with inferior ST-elevation myocardial infarction
      underwent primary percutaneous coronary intervention (PCI) within 3 h of symptom
      onset. She was preloaded with 300 mg aspirin and 600 mg clopidogrel before PCI.
      Coronary angiogram showed occlusion of the right coronary artery. During PCI,
      eptifibatide was initiated due to the large thrombus burden. Few hours after the
      procedure, on eptifibatide infusion, a severe drop in platelet count was observed
      (from 210,000/MUl to 35,000/MUl) and the infusion was discontinued. One hour
      later, still under eptifibatide effect and with severe thrombocytopenia, acute
      stent thrombosis developed. Lack of prior heparin exposure, quick onset of
      thrombocytopenia made heparin induced thrombocytopenia improbable that was later
      excluded by specific immunoassay. However, platelet function testing suggested
      that eptifibatide induced thrombocytopenia was mediated by activating
      autoantibodies since platelet reactivity was paradoxically very high at the time
      of stent thrombosis but decreased radically with eptifibatide washout. The
      patient was successfully managed without further complications on the basis of
      platelet function data obtained in the subsequent days. This rare subtype of
      thrombocytopenia highlights that not only platelet count but also platelet
      function should be closely monitored in case of severe thrombocytopenia to better
      balance bleeding and thrombosis.

PMID- 26305044
TI  - Australian dentists' perspectives on rapid HIV testing.
AB  - BACKGROUND: Fourteen per cent of people living with HIV in Australia, as in other
      countries, are not aware of their infection or their infective status. Dentists
      have the necessary expertise and are well-placed for access by those sections of
      the population who would not normally access screening for HIV. METHODS: A
      national cross-sectional online survey of 532 Australian dentists was conducted
      during the period June to October 2013. We surveyed dentists' understanding and
      willingness to undertake rapid HIV testing (RHT). RESULTS: The majority of
      respondents (65.1%) believed that RHT was needed in dental clinics, with
      approximately two-thirds of respondents indicating that RHT should be made
      available immediately. If RHT was to be undertaken in a dental setting, 51.1% of
      dentists thought that it should be conducted on saliva only, as opposed to blood
      or blood/saliva. Only 21.9% of dentists would currently be comfortable advising a
      patient of a reactive (i.e. positive) result indicative of HIV infection, with
      male dentists (26.1% comfortable) more comfortable than female dentists (17.5%
      comfortable) (p = 0.009). CONCLUSIONS: The majority of respondents were willing
      to provide RHT in their community settings. However, our data indicate that
      dentists would need additional training in HIV medicine, test administration and
      giving reactive results.

PMID- 26305045
TI  - One-pot Synthesis of Nitrogen and Phosphorus Co-doped Graphene and Its Use as
      High-performance Electrocatalyst for Oxygen Reduction Reaction.
AB  - In this study, N,P co-doped graphene (NPG) was prepared by a one-step pyrolysis
      using a mixture of graphene oxide and hexachlorocyclotriphosphazene (HCCP), in
      which HCCP was used as both the N and P source. Furthermore, it is shown that NPG
      electrodes, as efficient metal-free electrocatalysts, have a high onset
      potential, high current density, and long-term stability for the oxygen reduction
      reaction. 

PMID- 26305047
TI  - Development, Homeostasis, and Heterogeneity of NK Cells and ILC1.
AB  - Natural killer (NK) cells are a population of cytotoxic innate lymphocytes that
      evolved prior to their adaptive counterparts and constitute one of the first
      lines of defense against infected or mutated cells. NK cells are rapidly
      activated, expressing an array of germ-line encoded receptors that allow them to
      scan for protein irregularities on cells and kill those deemed "altered-self." NK
      cells rapidly produce a broad range of cytokines and chemokines following
      activation by virus, bacterial, or parasitic infection and are thus key in
      orchestrating inflammation. NK cells have previously been viewed to represent a
      relatively homogeneous group of IFN-gamma-producing cells that express the
      surface markers NK1.1 and natural killer cell p46-related protein (NKp46 or NCR1
      encoded by Ncr1) and depend on the transcription factor T-bet for their
      development. Recently, a second subset of T-bet-dependent innate cells, the group
      1 innate lymphoid cells (ILC1), has been discovered which share many attributes
      of conventional NK (cNK) cells. Despite the similarities between ILC1 and cNK
      cells , they differ in several important aspects including their localization,
      transcriptional regulation, and phenotype suggesting each subset has distinct
      origins and functions in immune responses. Previously, the ability to detect and
      spontaneously kill cells that exhibit "altered-self" which is central to tumor
      and viral immunity has been thought to be an attribute restricted solely to cNK
      cells. The identification of ILC1 challenges this notion and suggests that key
      contributions from ILC1 may have gone unrecognized. Thus, understanding the
      different rules that govern the behavior of ILC1 and cNK cells in immune
      responses may potentially open unexpected doorways to uncover novel strategies to
      manipulate these cells in treating disease. Here, we review recent advances in
      our understanding of peripheral cNK cell and ILC1 heterogeneity in terms of their
      development, phenotype, homeostasis, and effector functions. 

PMID- 26305048
TI  - Modeling studies on the uptake of hydrogen molecules by graphene.
AB  - Detailed ab initio molecular orbital calculations on the interactions of
      molecular hydrogen, H2, with various poly-aromatic hydrocarbons (PAHs) as a model
      system for graphene were carried out to accurately describe the physisorption
      phenomenon. The binding energies corrected for the basis set superposition error,
      DeltaEbind(BSSE), were obtained using the optimized geometries at the MP2 level
      with a large basis set and were compared with the single point binding energies,
      denoted as DeltaEbind(BSSE-s), using large basis sets on the geometries optimized
      at the small basis sets, such as SVP and TZVP. The calculations showed that the
      DeltaEbind(BSSE-s) values were similar to those at the MP2 level with the large
      basis sets. The binding strength increased gradually with increasing size of the
      PAHs. The DeltaEbind(BSSE-s) for an infinite graphene sheet was estimated to be 
      1.70 kcal mol(-1) using the non-linear curve fitting method. The present work
      could be expected to provide more useful and reliable information on H2
      physisorption.

PMID- 26305049
TI  - A computational study of the interaction between dopamine and DNA/RNA
      nucleosides.
AB  - The interaction between protonated dopamine and neutral RNA and DNA nucleosides
      was studied by means of density functional theory calculations in vacuum and in
      implicit water. On the most stable complexes formed with each of the nucleosides,
      the vertical absorption excitation energies were evaluated and compared with the
      values of separated dopamine and corresponding nucleoside. The most stable
      complex was formed with guanosine and the spectral changes in this complex
      resulted in a significant reduction of the oscillator strength of the first
      dopamine's transition. In the first guanosine's transition, a redshift of 0.2 eV
      was found combined with a reduction of the oscillator strength.

PMID- 26305046
TI  - Prix Fixe: Efferocytosis as a Four-Course Meal.
AB  - During development, stress, infection, or normal homeostasis, billions of cells
      die on a daily basis, and the responsibility of clearing these cellular corpses
      lies with the phagocytes of innate immune system. This process, termed
      efferocytosis , is critical for the prevention of inflammation and autoimmunity ,
      as well as modulation of the adaptive immune response. Defective clearance of
      dead cells is characteristic of many human autoimmune or autoinflammatory
      disorders, such as systemic lupus erythematosus (SLE), atherosclerosis, and
      diabetes. The mechanisms that phagocytes employ to sense, engulf, and process
      dead cells for an appropriate immune response have been an area of great
      interest. However, insight into novel mechanisms of programmed cell death , such
      as necroptosis, has shed light on the fact that while the diner (or phagocyte) is
      important, the meal itself (the type of dead cell) can play a crucial role in
      shaping the pursuant immune response.

PMID- 26305050
TI  - Disruption of the GABA shunt affects mitochondrial respiration and virulence in
      the cereal pathogen Fusarium graminearum.
AB  - The cereal pathogen Fusarium graminearum threatens food and feed production
      worldwide. It reduces the yield and poisons the remaining kernels with
      mycotoxins, notably deoxynivalenol (DON). We analyzed the importance of gamma
      aminobutanoic acid (GABA) metabolism for the life cycle of this fungal pathogen.
      GABA metabolism in F. graminearum is partially regulated by the global nitrogen
      regulator AreA. Genetic disruption of the GABA shunt by deletion of two GABA
      transaminases renders the pathogen unable to utilize the plant stress metabolites
      GABA and putrescine. The mutants showed increased sensitivity against oxidative
      stress, GABA accumulation in the mycelium, downregulation of two key enzymes of
      the TCA cycle, disturbed potential gradient in the mitochondrial membrane and
      lower mitochondrial oxygen consumption. In contrast, addition of GABA to the wild
      type resulted in its rapid turnover and increased mitochondrial steady state
      oxygen consumption. GABA concentrations are highly upregulated in infected wheat
      tissues. We conclude that GABA is metabolized by the pathogen during infection
      increasing its energy production, whereas the mutants accumulate GABA
      intracellularly resulting in decreased energy production. Consequently, the GABA
      mutants are strongly reduced in virulence but, because of their DON production,
      are able to cross the rachis node. 

PMID- 26305051
TI  - Children with Autism Show Altered Autonomic Adaptation to Novel and Familiar
      Social Partners.
AB  - Social deficits are fundamental to autism spectrum disorder (ASD), and a growing
      body of research implicates altered functioning of the autonomic nervous system
      (ANS), including both sympathetic and parasympathetic branches. However, few
      studies have explored both branches concurrently in ASD, particularly within the
      context of social interaction. The current study investigates patterns of change
      in indices of sympathetic (pre-ejection period; PEP) and parasympathetic
      (respiratory sinus arrhythmia; RSA) cardiac influence as boys (ages 8-11 years)
      with (N = 18) and without (N = 18) ASD engage in dyadic social interaction with
      novel and familiar social partners. Groups showed similar patterns of autonomic
      change during interaction with the novel partner, but differed in heart rate,
      PEP, and RSA reactivity while interacting with a familiar partner. Boys without
      ASD evinced decreasing sympathetic and increasing parasympathetic influence,
      whereas boys with ASD increased in sympathetic influence. Boys without ASD also
      demonstrated more consistent ANS responses across partners than those with ASD,
      with parasympathetic responding differentiating familiar and novel interaction
      partners. Finally, PEP slopes with a familiar partner correlated with boys'
      social skills. Implications include the importance of considering autonomic state
      during clinical assessment and treatment, and the potential value of regulation
      strategies as a complement to intervention programs aiming to support social
      cognition and behavior. Autism Res 2016, 9: 579-591. (c) 2015 International
      Society for Autism Research, Wiley Periodicals, Inc.

PMID- 26305053
TI  - Oscillatory Ventilator Performance: What Does It Mean?

PMID- 26305052
TI  - Proposed trial: safety and efficacy of resveratrol for the treatment of non
      alcoholic fatty liver disease (NAFLD) and associated insulin resistance in
      adolescents who are overweight or obese adolescents - rationale and protocol.
AB  - Non-alcoholic fatty liver (NAFL) disease (NAFLD) affects 30% of overweight
      adolescents and increases the risk of type 2 diabetes mellitus (T2D). Resveratrol
      is a naturally occurring compound with potential to reverse NAFL and its
      associated insulin resistance in adults. The use of resveratrol to reduce risk
      for T2D through its effect on NAFL has not been examined to date in youth. This
      paper provides a literature review and protocol for a 30 day proof of principle
      trial of resveratrol in a population of adolescents at risk for T2D. This
      randomized double-blind controlled trial is designed with the primary objective
      of evaluating a twice daily supplementation of 75 mg of resveratrol for safety
      and tolerability in overweight and obese adolescent subjects (13 to <18 years of
      age) with NAFL. Secondary objectives are to determine the effect size of the
      intervention on hepatic steatosis and whole body insulin sensitivity. Adolescents
      in the intervention arm (n = 10) will receive oral supplementation of resveratrol
      75 mg twice daily (with breakfast and dinner) for a total daily dose of 150 mg
      for the duration of 30 days. The comparison group (n = 10) will receive a placebo
      twice daily for 30 days. Both cases and controls will receive a standardized
      lifestyle intervention program. Subjects in both groups will be followed for an
      additional 30 days post intervention for total study duration of approximately 60
      days. Primary outcome measures include a primary side effect profile determined
      by participant interview, a side effect profile determined by serum biochemistry
      and vital signs. Secondary outcome measures include an oral glucose tolerance
      test, liver and cardiac fat content measured by magnetic resonance spectroscopy,
      anthropometric measures of overweight/obesity, inflammatory markers, and cardiac
      function and morphology measured with ultrasonography. Additional outcome
      measures include serum concentrations of resveratrol, compliance to protocol,
      physical activity, and nutritional assessment. This study will determine the
      safety and tolerability of resveratrol in an overweight adolescent population and
      inform the design of a larger randomized controlled trial.

PMID- 26305054
TI  - Kinesio taping of the deltoid does not reduce fatigue induced deficits in
      shoulder joint position sense.
AB  - BACKGROUND: Muscle fatigue is known to decrease shoulder proprioceptive acuity,
      potentially contributing to injuries. It has been suggested that Kinesio taping
      can improve proprioception. Therefore, the aim of this study was to investigate
      the effects of Kinesio taping on shoulder joint position sense after muscle
      fatigue. METHODS: Twenty-four healthy subjects were evaluated in a randomized,
      crossover, single-blind study design. Shoulder joint position sense was assessed
      during active repositioning tests at the target angles of 50 degrees , 70 degrees
      and 90 degrees  of arm elevation in scapular plane, in three sessions: control
      (no taping), Kinesio taping (Kinesio taping applied over the deltoid muscle with
      tension) and sham (Kinesio taping applied over deltoid without tension). Joint
      position sense was assessed three times: before taping; following taping
      application or rest, in the control session; and following a fatigue protocol.
      The constant error (repositioned angle-target angle) was considered for
      statistical analysis, using a 3-way repeated-measure ANOVA (within subject
      factors: taping, time and target angle). FINDINGS: There was no interaction or
      main effect involving taping. An interaction between time and angle was found and
      the simple effect showed that the constant error increased following fatigue at
      70 degrees  and 90 degrees , but not at 50 degrees . INTERPRETATION: The results
      of this study does not support the use of Kinesio taping applied over the deltoid
      muscle for compensating or preventing shoulder joint position sense deficits
      caused by muscle fatigue of shoulder abductors.

PMID- 26305055
TI  - Analysis of 40 weight loss compounds adulterated in health supplements by liquid
      chromatography quadrupole linear ion trap mass spectrometry.
AB  - In this study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) with
      scheduled multiple reaction monitoring (MRM) enhanced product ion (EPI) method
      was developed for simultaneous determination of 40 compounds with weight loss
      effect, including bisacodyl, phenolphthalein, and sibutramine and its
      metabolites, etc. They might be adulterated in health supplements to get
      prominent weight loss effect. The samples were analyzed using a Q-Trap 5500
      coupled with high performance liquid chromatography (HPLC) and a CORTECS ultra
      performance liquid chromatography (UPLC) C18 column (100 mm x 2.1 mm x1.6 um).
      Scheduled MRM was used as survey scan, MS2 spectra acquired in the EPI mode were
      used to perform library searching to increase the confidence of detection. Limits
      of detection were less than 10 ng/g for the majority of the analytes. A total of
      447 weight loss products were tested in our laboratory in the past three years.
      Among these samples, 119 samples were found to be adulterated with one or more
      weight loss compounds, including sibutramine, its metabolites benzyl sibutramine
      and desmethyl sibutramine; phenolphthalein; bisacodyl; furosemide; liothyronine
      (T3); and thyroxine (T4). Copyright (c) 2015 John Wiley & Sons, Ltd. 

PMID- 26305057
TI  - Calcitonin Gene-Related Peptide Receptor Blocker Inhibits Spontaneous Activity of
      Human Ureter.
AB  - Calcitonin gene-related peptide (CGRP) is present in nerve fibers that innervate
      the human ureter and may have important influence on the motility of this organ.
      The aim of our study was to investigate whether CGRP could affect the motility of
      an isolated human ureter. The tension and intraluminal pressure of the isolated
      ureteral segments were recorded and registered on a personal computer. Both
      phasic and tonic contractions of the isolated preparations were measured as area
      under the tension or pressure recordings. CGRP and CGRP fragment 8-37 were
      separately added to the organ baths in a cumulative way, thereby gradually
      increasing their concentration in the baths' solution. Alpha-CGRP did not affect
      either phasic, spontaneous activity or tone of isolated ureteral segments, as
      measured by both tension and intraluminal pressure. On the other hand, CGRP 8-37
      caused concentration-dependent inhibition of spontaneous contractions of the
      isolated ureteral segments. 

PMID- 26305056
TI  - Application of DNA adductomics to soil bacterium Sphingobium sp. strain KK22.
AB  - Toward the development of ecotoxicology methods to investigate microbial markers
      of impacts of hydrocarbon processing activities, DNA adductomic analyses were
      conducted on a sphingomonad soil bacterium. From growing cells that were exposed
      or unexposed to acrolein, a commonly used biocide in hydraulic fracturing
      processes, DNA was extracted, digested to 2'-deoxynucleosides and analyzed by
      liquid chromatography-positive ionization electrospray-tandem mass spectrometry
      in selected reaction monitoring mode transmitting the [M + H](+) > [M + H -
      116](+) transition over 100 transitions. Overall data shown as DNA adductome maps
      revealed numerous putative DNA adducts under both conditions with some occurring
      specifically for each condition. Adductomic analyses of triplicate samples
      indicated that elevated levels of some targeted putative adducts occurred in
      exposed cells. Two exposure-specific adducts were identified in exposed cells as
      3-(2'-deoxyribosyl)-5,6,7,8-tetrahydro-6-hydroxy-(and 8-hydroxy-)pyrimido[1,2-a]-
      purine-(3H)-one (6- and 8-hydroxy-PdG) following synthesis of authentic standards
      of these compounds and subsequent analyses. A time course experiment showed that
      6- and 8-hydroxy-PdG were detected in bacterial DNA within 30 min of acrolein
      exposure but were not detected in unexposed cells. This work demonstrated the
      first application of DNA adductomics to examine DNA damage in a bacterium and
      sets a foundation for future work.

PMID- 26305058
TI  - The femoral neck-shaft angle on plain radiographs: a systematic review.
AB  - OBJECTIVE: The femoral neck-shaft angle (NSA) is an important measure for the
      assessment of the anatomy of the hip and planning of operations. Despite its
      common use, there remains disagreement concerning the method of measurement and
      the correction of hip rotation and femoral version of the projected NSA on
      conventional radiographs. We addressed the following questions: (1) What are the
      reported values for NSA in normal adult subjects and in osteoarthritis? (2) Is
      there a difference between non-corrected and rotation-corrected measurements? (3)
      Which methods are used for measuring the NSA on plain radiographs? (4) What could
      be learned from an analysis of the intra- and interobserver reliability? MATERIAL
      AND METHODS: A systematic literature search was performed including 26
      publications reporting the measurement of the NSA on conventional radiographs.
      RESULTS: The mean NSA of healthy adults (5,089 hips) was 128.8 degrees  (98-180
      degrees ) and 131.5 degrees  (115-155 degrees ) in patients with osteoarthritis
      (1230 hips). The mean NSA was 128.5 degrees  (127-130.5 degrees ) for the
      rotation-corrected and 129.5 degrees  (119.6-151 degrees ) for the non-corrected
      measurements. CONCLUSION: Our data showed a high variance of the reported neck
      shaft angles. Notably, we identified the inconsistency of the published methods
      of measurement as a central issue. The reported effect of rotation-correction
      cannot be reliably verified.

PMID- 26305059
TI  - Throwing-related injuries of the subscapularis in professional baseball players.
AB  - OBJECTIVE: To describe the MR appearance of a series of throwing-related injuries
      to the subscapularis muscle-tendon complex among baseball players. MATERIALS AND
      METHODS: A retrospective review of MR scans of the shoulder in players from 1
      professional baseball organization over the course of 5 years was performed to
      identify cases with findings suggestive of subscapularis injury. These findings
      were graded and the medical record was reviewed to assess clinical findings,
      treatment, and follow-up. Preinjury baseline measurements of arm external
      rotation at 90 degrees  of abduction were compared to measurements from a
      noninjured cohort to evaluate whether this measure is a risk factor for injury.
      RESULTS: A total of 133 MR scans of the shoulder were evaluated. Eleven of the
      scans demonstrated signal changes suggesting subscapularis injury; 10 of these 11
      patients had clinical findings supporting a diagnosis of throwing-related
      subscapularis strain. There were four grade 1, four grade 2, and two grade 3
      injuries. All injuries occurred in the inferior half of the subscapularis at the
      myotendinous junction. Risk of subscapularis injury increased with lower levels
      of dominant arm external rotation (odds ratio, 1.12; 95% CI, 1.07-1.21; p <
      0.001). A threshold of dominant arm external rotation of <106 degrees 
      demonstrated sensitivity of 0.700 (95% CI, 0.392-0.897) and specificity of 0.951
      (95% CI, 0.888-0.982) for subscapularis injury. CONCLUSION: Throwing-related
      subscapularis injuries occur in the inferior half of the muscle at the
      myotendinous junction. Our data suggest that there is an increased risk of these
      injuries with lower levels of dominant arm external rotation.

PMID- 26305062
TI  - Erratum to: Arteria praebronchialis found on MDCT: potentially dangerous aberrant
      artery supplying the left lower lobe.

PMID- 26305060
TI  - Immunogenetics of juvenile idiopathic arthritis: A comprehensive review.
AB  - Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory
      arthropathy of childhood. Juvenile idiopathic arthritis is believed to be a
      complex genetic trait influenced by both genetic and environmental factors. Twin
      and family studies suggest a substantial role for genetic factors in the
      predisposition to JIA. Describing the genetics is complicated by the
      heterogeneity of JIA; the International League of Associations for Rheumatology
      (ILAR) has defined seven categories of JIA based on distinct clinical and
      laboratory features. Utilizing a variety of techniques including candidate gene
      studies, the use of genotyping arrays such as Immunochip, and genome wide
      association studies (GWAS), both human leukocyte antigen (HLA) and non-HLA
      susceptibility loci associated with JIA have been described. Several of these
      polymorphisms (e.g. HLA class II, PTPN22, STAT4) are shared with other common
      autoimmune conditions; other novel polymorphisms that have been identified may be
      unique to JIA. Associations with oligoarticular and RF-negative polyarticular JIA
      are the best characterized. A strong association between HLA DRB1:11:03/04 and
      DRB1:08:01, and a protective effect of DRB1:15:01 have been described. HLA
      DPB1:02:01 has also been associated with oligoarticular and RF-negative
      polyarticular JIA. Besides PTPN22, STAT4 and PTPN2 variants, IL2, IL2RA, IL2RB,
      as well as IL6 and IL6R loci also harbor variants associated with oligoarticular
      and RF-negative polyarticular JIA. RF-positive polyarticular JIA is associated
      with many of the shared epitope encoding HLA DRB1 alleles, as well as PTPN22,
      STAT4 and TNFAIP3 variants. ERA is associated with HLA B27. Most other
      associations between JIA categories and HLA or non-HLA variants need
      confirmation. The formation of International Consortia to ascertain and analyze
      large cohorts of JIA categories, validation of reported findings in independent
      cohorts, and functional studies will enhance our understanding of the genetic
      underpinnings of JIA.

PMID- 26305061
TI  - Epidermal injury promotes nephritis flare in lupus-prone mice.
AB  - Systemic lupus erythematosus is clinically characterized by episodes of flare and
      remission. In patients, cutaneous exposure to ultraviolet light has been proposed
      as a flare trigger. However, induction of flare secondary to cutaneous exposure
      has been difficult to emulate in many murine lupus models. Here, we describe a
      system in which epidermal injury is able to trigger the development of a lupus
      nephritis flare in New Zealand Mixed (NZM) 2328 mice. 20-week old NZM2328 female
      mice underwent removal of the stratum corneum via duct tape, which resulted in
      rapid onset of proteinuria and death when compared to sham-stripped littermate
      control NZM2328 mice. This was coupled with a drop in serum C3 concentrations and
      dsDNA antibody levels and enhanced immune complex deposition in the glomeruli.
      Recruitment of CD11b(+)CD11c(+)F4/80(high) macrophages and
      CD11b(+)CD11c(+)F4/80(low) dendritic cells was noted prior to the onset of
      proteinuria in injured mice. Transcriptional changes within the kidney suggest a
      burst of type I IFN-mediated and inflammatory signaling which is followed by
      upregulation of CXCL13 following epidermal injury. Thus, we propose that tape
      stripping of lupus-prone NZM2328 mice is a novel model of lupus flare induction
      that will allow for the study of the role of cutaneous inflammation in lupus
      development and how crosstalk between dermal and systemic immune systems can lead
      to lupus flare. 

PMID- 26305063
TI  - A systematic review and meta-analysis of cognitive remediation in early
      schizophrenia.
AB  - Neurocognitive impairment predicts disability in schizophrenia, making
      intervention theoretically attractive as a means to minimise chronic disability.
      Many trials confirm that cognitive remediation (CR) produces meaningful, durable
      improvements in cognition and functioning but fewer focus on the early stages. We
      systematically reviewed CR trials in early schizophrenia to determine its
      efficacy on global cognition, functioning and symptoms. Two reviewers
      independently searched electronic databases to identify randomised controlled
      trials investigating CR following a first episode of psychosis. Eleven trials
      with 615 participants were identified. Random effect models revealed a non
      significant effect of CR on global cognition (effect size=0.13, 95% CI -0.04,
      0.31; p0.14), p<0.05 in sensitivity analysis (effect size 0.19; CI 0.00, 0.38).
      One of seven neurocognitive domains showed a significant positive effect (verbal
      learning and memory) and five others showed borderline significant benefits.
      There was a significant effect on functioning (0.18; CI 0.01, 0.36; p<0.05) and
      symptoms (0.19; CI 0.02, 0.36; p<0.05). CR's effect on functioning and symptoms
      was larger in trials with adjunctive psychiatric rehabilitation and small group
      interventions. CR's effect sizes in early illness were smaller than those in
      chronic schizophrenia, perhaps because of participants' reduced scope for
      improvement, though trials' small number and size produces uncertain estimates of
      effect. However, significant benefits were seen in functioning and symptoms and
      moderator analyses indicate factors that may increase CR's effect. Findings here,
      theoretical considerations and trials in chronic schizophrenia suggest that
      targeting social cognition might also enhance its efficacy. 

PMID- 26305064
TI  - Long-Term Response to Cholinesterase Inhibitor Treatment Is Related to Functional
      MRI Response in Alzheimer's Disease.
AB  - BACKGROUND: Treatment of Alzheimer's disease (AD) with cholinesterase inhibitors
      (ChEI) enhances cholinergic activity and alleviates clinical symptoms. However,
      there is variation in the clinical response as well as system level changes
      revealed by functional MRI (fMRI) studies. METHODS: We investigated 18 newly
      diagnosed mild AD patients with fMRI using a face recognition task after a single
      oral dose of rivastigmine, a single dose of placebo and 1-month treatment with
      rivastigmine. The clinical follow-up took place at 6 and 12 months. RESULTS: MMSE
      score difference between baseline and the follow-ups showed a positive
      correlation with fMRI activation difference between treatment and placebo in the
      right prefrontal cortex. A negative correlation was found for the left prefrontal
      cortex and the left fusiform gyrus. In addition, greater signal intensity in the
      right versus the left fusiform gyrus predicted a response to ChEI with increasing
      MMSE scores during the follow-up with 77.8% sensitivity and 77.8% specificity.
      CONCLUSIONS: The increased fMRI activation by cholinergic stimulation in brain
      areas associated with the processing of the visual task reveals still functioning
      brain networks and a subsequent positive effect of ChEI on cognition. Thus, fMRI
      may be useful for identifying AD patients most likely to respond to treatment
      with ChEI.

PMID- 26305065
TI  - Primary Rectal Mucosa-Associated Lymphoid Tissue Lymphoma.

PMID- 26305066
TI  - The Epidemiology of Liver Diseases Unique to Pregnancy in a US Community: A
      Population-Based Study.
AB  - BACKGROUND & AIMS: Little is known in the United States about the epidemiology of
      liver diseases that develop only during (are unique to) pregnancy. We
      investigated the incidence of liver diseases unique to pregnancy in Olmsted
      County, Minnesota, and long-term maternal and fetal outcomes. METHODS: We
      identified 247 women with liver diseases unique to pregnancy from 1996 through
      2010 using the Rochester Epidemiology Project database. The crude incidence rate
      was calculated by the number of liver disease cases divided by 35,101
      pregnancies. RESULTS: Of pregnant women with liver diseases, 134 had preeclampsia
      with liver dysfunction, 72 had hemolysis-associated increased levels of liver
      enzymes and low-platelet (HELLP) syndrome, 26 had intrahepatic cholestasis of
      pregnancy, 14 had hyperemesis gravidarum with abnormal liver enzymes, and 1 had
      acute fatty liver of pregnancy. The crude incidence of liver diseases unique to
      pregnancy was 0.77%. Outcomes were worse among women with HELLP or preeclampsia
      than the other disorders--of women with HELLP, 70% had a premature delivery, 4%
      had abruptio placentae, 3% had acute kidney injury, and 3% had infant death. Of
      women with preeclampsia, 56.0% had a premature delivery, 4% had abruptio
      placentae, 3% had acute kidney injury, and 0.7% had infant death. After 7 median
      years of follow-up (range, 0-18 years), 14% of the women developed recurrent
      liver disease unique to pregnancy; the proportions were highest in women with
      initial hyperemesis gravidarum (36%) or intrahepatic cholestasis of pregnancy
      (35%). Women with preeclampsia were more likely to develop subsequent
      hepatobiliary diseases. CONCLUSIONS: We found the incidence of liver disease
      unique to pregnancy in Olmsted County, Minnesota, to be lower than that reported
      from Europe or US tertiary referral centers. Maternal and fetal outcomes in
      Olmsted County were better than those reported from other studies, but fetal
      mortality was still high (0.7%-3.0%). Women with preeclampsia or HELLP are at
      higher risk for peripartum complications and subsequent development of
      comorbidities.

PMID- 26305067
TI  - A Variant in PNPLA3 Associated With Fibrosis Progression but not Hepatocellular
      Carcinoma in Patients With Hepatitis C Virus Infection.
AB  - BACKGROUND & AIMS: A single nucleotide polymorphism (SNP) in the patatin-like
      phospholipase domain containing 3 gene (PNPLA3, rs738409) has been associated
      with fibrosis and development of hepatocellular carcinoma (HCC) in patients with
      nonalcoholic steatohepatitis, although its association with outcomes in patients
      with hepatitis C virus (HCV) infection is less clear. We evaluated the
      association between this SNP in PNPLA3 and fibrosis progression and development
      of HCC among HCV-infected patients. METHODS: We performed a secondary analysis of
      data from participants in the Hepatitis C Antiviral Long-Term Treatment against
      Cirrhosis (HALT-C) trial. Patients were randomly assigned to groups given weekly
      pegylated interferon or no further therapy for 3.5 y and then followed without
      further treatment until October 2009. Multivariate logistic regression was used
      to identify factors associated with fibrosis at baseline, fibrosis progression
      (defined as 2-point increase in Ishak score), and HCC development. RESULTS: Among
      937 HCV patients with known PNPLA3 genotype, 384 (41.0%) had cirrhosis at
      baseline. The PNPLA3 CG/GG SNP at rs738409 was significantly associated with the
      presence of cirrhosis (odds ratio [OR], 1.76; 95% confidence interval [CI], 1.34
      2.30), after adjusting for age, sex, diabetes, and race. Among 493 patients
      without cirrhosis at baseline who had at least 1 follow-up biopsy, 142 had
      fibrosis progression. In multivariate analyses, fibrosis progression was
      associated with obesity (OR, 1.67; 95% CI, 1.11-2.51) and the PNPLA3 CG/GG
      genotype (OR, 1.70; 95% CI, 1.13-2.56). PNPLA3 genotype was not associated with
      HCC development (P = .85). Using these data to update prior meta-analysis
      results, the rs738409 SNP in PNPLA3 was not significantly associated with
      development of HCC in HCV-infected patients (OR 1.29; 95% CI, 0.97-1.99).
      CONCLUSIONS: Based on data from the HALT-C trial, the PNPLA3 CG/GG SNP at
      rs738409 is associated with fibrosis progression but not development of HCC in
      patients with HCV infection.

PMID- 26305068
TI  - Patient-reported Outcomes After Conservative or Surgical Management of Recurrent
      and Chronic Complaints of Diverticulitis: Systematic Review and Meta-analysis.
AB  - BACKGROUND & AIMS: Patients with diverticulitis develop recurrences and chronic
      abdominal symptoms. Recurrent diverticulitis is seldom complicated, which has led
      to a conservative treatment approach. However, some studies suggest that surgical
      intervention reduces recurrence and chronic abdominal problems. We conducted a
      systematic review and meta-analysis of quality of life (QOL) and other patient
      reported outcomes (PROs) after conservative vs surgical treatment of
      uncomplicated diverticulitis. METHODS: We searched the CENTRAL, MEDLINE, EMBASE,
      and PsycInfo databases for randomized trials and cohort studies reporting on QOL
      or other PROs after conservative or operative treatment for uncomplicated
      diverticulitis from January 1990 through May 2014. Eight PROs were defined and
      graded according to their clinical relevance. Risk of bias was assessed by using
      the Cochrane Collaboration tool. Subgroup and sensitivity analyses were performed
      to test the robustness of the results. The review protocol was registered through
      PROSPERO (CRD42013005854). RESULTS: We analyzed data from 21 studies that
      comprised 1858 patients; all studies had a high risk of bias. There were no head
      to-head comparisons of gastrointestinal symptoms or general QOL between elective
      surgical vs conservative treatment of recurrent diverticulitis. On the basis of
      Short-Form 36 scores, patients had higher QOL scores after elective laparoscopic
      resection (73.4; 95% confidence interval [CI], 65.7-81.1) than conservative
      treatment (58.1; 95% CI, 47.2-69.1). A lower proportion of patients had
      gastrointestinal symptoms after laparoscopic surgery (9%; 95% CI, 4%-14%) than
      conservative treatment (36%; 95% CI, 27%-45%) in all cohorts and in 1 trial
      comparing these treatments (odds ratio, 0.35; 95% CI, 0.16-0.7). The proportion
      of patients with chronic abdominal pain after elective laparoscopy was 11% (95%
      CI, 1%-21%) compared with 38% (95% CI, 19%-56%) after conservative treatment.
      CONCLUSIONS: On the basis of a systematic review and meta-analysis, patients have
      better QOL and fewer symptoms after laparoscopic surgery vs conservative
      treatment. However, studies of PROs for treatment of diverticulitis were of low
      quality.

PMID- 26305069
TI  - Isolated Focal Herniation of Pancreatic Body Through Esophageal Hiatus in a
      Patient With Scoliosis.

PMID- 26305070
TI  - Unravelling the Riddle of Gastroesophageal Reflux Disease, Obesity, and Barrett's
      Esophagus.

PMID- 26305071
TI  - Factors Associated With Missed and Cancelled Colonoscopy Appointments at Veterans
      Health Administration Facilities.
AB  - BACKGROUND & AIMS: Cancelled and missed colonoscopy appointments waste resources,
      increase colonoscopy delays, and can adversely affect patient outcomes. We
      examined individual and organizational factors associated with missed and
      cancelled colonoscopy appointments in Veteran Health Administration facilities.
      METHODS: From 69 facilities meeting inclusion criteria, we identified 27,994
      patients with colonoscopy appointments scheduled for follow-up, on the basis of
      positive fecal occult blood test results, between August 16, 2009 and September
      30, 2011. We identified factors associated with colonoscopy appointment status
      (completed, cancelled, or missed) by using hierarchical multinomial regression.
      Individual factors examined included age, race, sex, marital status, residence,
      drive time to nearest specialty care facility, limited life expectancy,
      comorbidities, colonoscopy in the past decade, referring facility type, referral
      month, and appointment lead time. Organizational factors included facility
      region, complexity, appointment reminders, scheduling, and prep education
      practices. RESULTS: Missed appointments were associated with limited life
      expectancy (odds ratio [OR], 2.74; P = .0004), no personal history of polyps (OR,
      2.74; P < .0001), high facility complexity (OR, 2.69; P = .007), dual diagnosis
      of psychiatric disorders and substance abuse (OR, 1.82; P < .0001), and opt-out
      scheduling (OR, 1.57; P = .02). Cancelled appointments were associated with age
      (OR, 1.61; P = .0005 for 85 years or older and OR, 1.44; P < .0001 for 65-84
      years old), no history of polyps (OR, 1.51; P < .0001), and opt-out scheduling
      (OR, 1.26; P = .04). Additional predictors of both outcomes included race,
      marital status, and lead time. CONCLUSIONS: Several factors within Veterans
      Health Administration clinic control can be targeted to reduce missed and
      cancelled colonoscopy appointments. Specifically, developing systems to minimize
      referrals for patients with limited life expectancy could reduce missed
      appointments, and use of opt-in scheduling and reductions in appointment lead
      time could improve both outcomes.

PMID- 26305072
TI  - An Incidental Finding of Esophageal Parakeratosis.

PMID- 26305073
TI  - Buprenorphine infrequently found in fatal overdose in New York City.
AB  - BACKGROUND: Buprenorphine is an opioid agonist medication that is both safe and
      effective in the treatment of opioid use disorders and the prevention of opioid
      overdoses. Despite this, media coverage has highlighted public concerns about the
      potential safety consequences of buprenorphine misuse and diversion. To address
      the possible contribution of buprenorphine to overdose mortality, we
      systematically tested post mortem blood specimens from decedents who had died of
      an unintentional drug overdoses in 2013. METHODS: We retrospectively tested
      consecutive drug overdose cases that occurred from June through October 2013.
      Cases with available blood specimens were tested for buprenorphine and
      norbuprenorphine using liquid chromatography-tandem mass spectrometry. Toxicology
      results were linked to death certificates and case files from New York City Vital
      Statistics and New York City Office of the Chief Medical Examiner. RESULTS: Of
      the 98 unintentional drug overdose fatalities tested, only 2 (2.0%) tested
      positive for buprenorphine metabolites. All 98 unintentional fatalities involved
      multiple substances. CONCLUSIONS: Buprenorphine was infrequently found in drug
      overdose deaths in New York City. Since the safety and efficacy of buprenorphine
      are well documented, and overdoses resulting from buprenorphine treatment or
      diversion are very rare, facilitating access to buprenorphine treatment is
      strongly recommended.

PMID- 26305074
TI  - Cigarette smoking and alcohol use as predictors of disability retirement: A
      population-based cohort study.
AB  - BACKGROUND: This study investigated how cigarette smoking and alcohol use predict
      disability retirement. METHODS: Data from the longitudinal nationwide Finnish
      Twin Cohort study were analyzed, with clustered study design applied when
      computing 95% confidence intervals (CI). The sample included 21,719 individuals.
      Smoking and alcohol use were assessed with a questionnaire in 1975. Registry data
      on retirement events up till end of 2004 were obtained from the Social Insurance
      Institution and the Finnish Centre for Pensions. RESULTS: Disability pension was
      granted to 4251 participants. Among men, adjusted for age and alcohol use, former
      (HR=1.45, 95%CI 1.28, 1.65, p<.001) and daily smokers (HR=1.93, 95%CI 1.71, 2.17,
      p<.001) showed elevated disability pension risk compared to never smokers. Among
      women, daily smokers (HR=1.25, 95%CI 1.11, 1.40, <.001) had elevated risk. The
      age and smoking adjusted risk estimates for alcohol were elevated among
      abstainers (men HR=1.41, 95%CI 1.21, 1.65, p<.001; women HR=1.36, 95%CI 1.23,
      1.52, p<.001) and heavy drinkers (men HR=1.30, 95%CI 1.18, 1.43, p<.001; women
      HR=1.34, 95%CI 1.04, 1.72, p=.026). Those being persistent smokers and binge
      drinkers had over three-fold disability risk compared to those who were binge
      drinkers but had only a few smoking years (men: HR=3.32, 95%CI 2.43, 4.54,
      p<.001; women: HR=4.05, 95%CI 2.05, 8.00, p<.001). Among men and women who were
      not binge drinkers, longer smoking duration was needed for elevated disability
      risk. CONCLUSIONS: Both smoking and excess alcohol use significantly predict
      disability retirement. In order to extend working careers, more attention should
      be paid to health behaviors, in addition to working conditions.

PMID- 26305075
TI  - Robotic right colectomy with intracorporeal anastomosis--a video vignette.

PMID- 26305076
TI  - Effect of adipose-derived mesenchymal stromal cells on tendon healing in aging
      and estrogen deficiency: an in vitro co-culture model.
AB  - BACKGROUND AIMS: Aging and estrogen deficiency play a pivotal role in reducing
      tenocyte proliferation, collagen turnover and extracellular matrix remodeling.
      Mesenchymal stromal cells are being studied as an alternative for tendon
      regeneration, but little is known about the molecular events of adipose-derived
      mesenchymal stromal cells (ADSCs) on tenocytes in tendons compromised by aging
      and estrogen deficiency. The present in vitro study aims to compare the potential
      therapeutic effects of ADSCs, harvested from healthy young (sham) and aged
      estrogen-deficient (OVX) subjects, for tendon healing. METHODS: An indirect co
      culture system was set up with ADSCs, isolated from OVX or sham rats, and
      tenocytes from OVX rats. Cell proliferation, healing rate and gene expression
      were evaluated in both a standard culture condition and a microwound-healing
      model. RESULTS: It was observed that tenocyte proliferation, healing rate and
      collagen expression improved after the addition of sham ADSCs in both culture
      situations. OVX ADSCs also increased tenocyte proliferation and healing rate but
      less compared with sham ADSCs. Decorin and Tenascin C expression increased in the
      presence of OVX ADSCs. CONCLUSIONS: Findings suggest that ADSCs might be a
      promising treatment for tendon regeneration in advanced age and estrogen
      deficiency. However, some differences between allogenic and autologous cells were
      found and should be investigated in further in vivo studies. It appears that
      allogenic ADSCs improve tenocyte proliferation, collagen expression and the
      healing rate more than autologous cells. Autologous cells increase collagen
      expression only in the absence of an injury and increase Decorin and Tenascin C
      more than allogenic cells.

PMID- 26305077
TI  - Behavioral Healthcare Staff Attitudes and Practices Regarding Consumer Tobacco
      Cessation Services.
AB  - Given the high prevalence of tobacco use among persons with behavioral health
      disorders, there has been much discussion about if and when tobacco cessation
      services should be provided to consumers. Approximately 1700 staff (who served
      adults and youth) from 38 public behavioral healthcare agencies in Virginia
      completed a survey on their attitudes and practices regarding tobacco cessation
      services for consumers. Results showed that most staff (88%) think tobacco
      cessation services should be offered and do not interfere with treatment. Most
      staff (57%) always/usually screened consumers for tobacco use, but few (14%)
      always/usually provided tobacco cessation counseling. Reported barriers included
      consumers not wanting to quit and a lack of staff training. Most staff reported
      that their organizations do not have policies regarding tobacco cessation
      services. Use of tobacco cessation practices was related to staff confidence
      using the practices, preparedness, and years of experience. Steps to improving
      the use of tobacco cessation practices in this setting are discussed.

PMID- 26305078
TI  - IgA Dominant Post-infectious Glomerulonephritis in a 12-year-old Child.

PMID- 26305079
TI  - Sepsis on the AMU - Time to Pick up the Baton.

PMID- 26305080
TI  - Doctors' Knowledge of Viral Haemorrhagic Fevers.
AB  - Viral Haemorrhagic Fevers (VHF) such as Ebola Virus Disease (EVD) are of
      increasing concern to clinicians and public heath bodies across Europe and
      America due to the on-going epidemic in West Africa. We conducted an online study
      to assess clinicians' knowledge of VHF across six hospital sites in London. This
      showed suboptimal knowledge of Public Health England guidance, EVD epidemiology
      and the risk factors for acquiring VHF. Knowledge about VHF was dependent on
      seniority of grade with the most junior grade of doctors performing worse in
      several areas of the survey. Poor knowledge raises concerns that those at risk of
      VHF will be inappropriately risk stratified and managed. Education of doctors and
      other healthcare professionals about VHF is necessary to address these knowledge
      gaps. 

PMID- 26305081
TI  - PRISMA Analysis of 30 Day Readmissions to a Tertiary Cancer Hospital.
AB  - BACKGROUND: Hospital readmissions are increasingly used as a quality indicator.
      Patients with cancer have an increased risk of readmission. The purpose of this
      study was to develop an in depth understanding of the causes of readmissions in
      patients undergoing cancer treatment using PRISMA methodology and was
      subsequently used to identify any potentially preventable causes of readmission
      in this cohort. METHODS: 50 consecutive 30 day readmissions from the 1st November
      2014 to the medical admissions unit (MAU) at a specialist tertiary cancer
      hospital in the Northwest of England were analysed retrospectively. RESULTS:
      Q25(50%) of the patients were male with a median age of 59 years (range 19-81).
      PRISMA analysis showed that active (human) factors contributed to the readmission
      of 4 (8%) of the readmissions, which may have been potentially preventable. All
      of the readmissions were driven by a medical condition related to the patient's
      underlying cancer and ongoing cancer treatment. CONCLUSIONS: The majority of
      readmissions of patients undergoing cancer treatment appear to be related to the
      underlying condition and, as such, are predictable but not preventable. This
      suggests that hospital readmission is not a good quality indicator in this cohort
      of patients.

PMID- 26305082
TI  - How do junior doctors spend their time in an Acute Medical Unit?

PMID- 26305083
TI  - Viewpoint: What is 'Training'?
AB  - This edition's paper on 'How doctors spend their time on an AMU' defines
      'training' as time spent on senior ward rounds. But the idea that senior ward
      rounds are training and the rest of work is not is a huge assumption that must be
      challenged. This article explores some false ideas about postgraduate medical
      education; why teaching and learning activities needs to be made more explicit,
      and why we need to stop talking about 'training' and start talking about
      learning. The goal of professional education is expertise, not competence. That
      can only happen through work-based learning, something to which we need to pay
      much more attention. 

PMID- 26305084
TI  - Pleuro-Peritoneal Fistula - An Important Condition to Consider in Patients using
      Peritoneal Dialysis.
AB  - Pleural effusions are a common finding in patients admitted on the medical take.
      This case decribes a patient using peritoneal dialysis who presented with
      progressive dyspnoea. Clinical examination and chest x-ray confirmed the presence
      of a pleural effusion. Thoracocentesis confirmed a 'sweet' effusion (higher
      pleural: serum glucose content), suggesting a pleuro-peritoneal leak. Optimal
      management involved switch from peritoneal to haemodialysis and referral to a
      specialised renal unit. This case highlights the need to consider the diagnosis
      of pleuro-peritoneal leak in patients using peritoneal dialysis who present to
      the acute medical unit with pleural effusion. 

PMID- 26305085
TI  - Low Oxygen Affinity Variant Haemoglobin in an elderly woman presenting with low
      oxygen saturation.
AB  - An asymptomatic 81-year-old woman was referred by her general practitioner
      regarding a pulse-oximetry oxygen saturation (SpO2) of 74%. An arterial blood gas
      analysis (ABG) on air showed PaO2 12.9 kPa, oxygen saturation 80%, with normal
      pH, PaCO2, methaemoglobin and carboxyhaemoglobin levels. After a normal chest x
      ray, tinzaparin was administered empirically for possible occult pulmonary
      embolus. This diagnosis was subsequently excluded with an unremarkable computed
      tomography pulmonary angiogram (CTPA). She was further investigated as an out
      patient. DNA globin-gene analysis identified a variant haemoglobin revealed to be
      haemoglobin Saint Mande (HbSM). Following reassurance regarding the benign nature
      of her condition, she has remained well. 

PMID- 26305086
TI  - Acute Internal Medicine Trainee Survey 2015.
AB  - OBJECTIVES: To ascertain current Acute Internal Medicine (AIM) trainees' opinions
      on their training programme, practical procedures, specialist skills and AIM as a
      specialty. This can then be used to feedback to the national training committee
      to help shape training priorities. METHODS: Online survey sent to all AIM Higher
      Specialty Trainees registered on the Society for Acute Medicine database, and
      advertised through e-mail communication and social media. RESULTS: The majority
      of trainees (55.5%) were quite happy or very happy with their training currently,
      although significant difficulties were highlighted with time off for specialist
      skill training and difficulty achieving certain procedural skills. The majority
      of trainees believe ultrasound should form a core component of AIM training
      (82.3%). A high proportion of trainees would recommend AIM as a specialty despite
      these difficulties. CONCLUSIONS: A number of issues were highlighted causing
      difficulties within AIM training, despite which the vast majority of trainees
      would recommend AIM as a career choice. The results were fed back to the training
      committee in March.

PMID- 26305087
TI  - Problem-Based Review: Non Vitamin K Antagonist Oral Anticoagulants for the Acute
      Physician.
AB  - Non-vitamin K antagonist oral anticoagulants (NOACs), are direct anticoagulants
      which inhibit specific coagulation factors and function as anticoagulants. Three
      NOACs are currently licensed in the United Kingdom: dabigatran, a thrombin
      inhibitor, and rivaroxaban and apixaban, antagonists of factor Xa. They are set
      to change the anticoagulant landscape, which was previously ruled by warfarin and
      heparins. Their advantages including oral formulations, rapid onset and offset of
      action, predictable pharmacokinetics, no requirement for routine blood monitoring
      or dose adjustment and very few drug interactions. The increasing use of these
      drugs means the acute medicine physicians are likely to encounter patients who
      have been taking them. This article reviews some of the challenging clinical
      situations in which this may arise. 

PMID- 26305088
TI  - Reasons for living, meaning in life, and suicide ideation: investigating the
      roles of key positive psychological factors in reducing suicide risk in community
      residing older adults.
AB  - OBJECTIVES: To investigate the roles of reasons for living (RFL) and meaning in
      life (MIL) in potentially promoting mental health and well-being and protecting
      against suicide ideation among community-residing older adults and to investigate
      the psychometric properties of the Reasons for Living Scale-Older Adult version
      (RFL-OA). METHOD: Of 173 older adults initially recruited into a longitudinal
      study on late-life suicide ideation, 109 completed the RFL-OA and measures of
      cognitive and physical functioning and positive and negative psychological
      factors at a two-year follow-up assessment. We tested a model in which RFL and
      MIL protect against suicide ideation, controlling for demographic and clinical
      factors. We also assessed the psychometric properties of the RFL-OA in community
      residing older adults, investigating its internal consistency and its convergent
      (MIL, perceived social support, and life satisfaction), divergent (loneliness,
      depressive symptom severity, and suicide ideation), and discriminant validity
      (cognitive and physical functioning). RESULTS: RFL-OA scores explained
      significant variance in suicide ideation, controlling for age, sex, depressive
      symptom severity, and loneliness. MIL explained significant unique variance in
      suicide ideation, controlling for these factors and RFL, and MIL significantly
      mediated the association between RFL and suicide ideation. Psychometric analyses
      indicated strong internal consistency (alpha = .94), convergent, divergent, and
      discriminant validity for the RFL-OA relative to positive and negative
      psychological factors and cognitive and physical functioning. CONCLUSION: These
      findings add to a growing body of literature suggesting merit in investigating
      positive psychological factors together with negative factors when assessing
      suicide risk and planning psychological services for older adults.

PMID- 26305090
TI  - Greater basal skeletal muscle AMPKalpha phosphorylation in men than in women:
      Associations with anaerobic performance.
AB  - OBJECTIVES: This study was designed to investigate the association of gender,
      fibre type composition, and anaerobic performance with the basal skeletal muscle
      signalling cascades regulating muscle phenotype. DESIGN: Muscle biopsies were
      obtained from 25 men and 10 women all young and healthy. METHODS: Protein
      phosphorylation of Thr(172)AMPKalpha, Ser(221)ACCbeta, Thr(286)CaMKII as well as
      total protein abundance of PGC-1alpha, SIRT1, and CnA were measured by Western
      blot and anaerobic performance by the Wingate test. RESULTS: Percent type I
      myosin heavy chain (MHC I) was lower in men (37.1 +/- 10.4 vs. 58.5 +/- 12.5, P <
      .01). Total, free testosterone and free androgen index were higher in men (11.5,
      36.6 and 40.6 fold, respectively, P < .01). AMPKalpha phosphorylation was 2.2
      fold higher in men compared to women (P < .01). Total Ser(221)ACCbeta and
      Thr(286)CaMKII fractional phosphorylation tended to be higher in men (P = .1).
      PGC1-alpha and SIRT1 total protein expression was similar in men and women,
      whereas CnA tended to be higher in men (P = .1). Basal AMPKalpha phosphorylation
      was linearly related to the percentage of MHC I in men (r = 0.56; P < .01), but
      not in women. No association was observed between anaerobic performance and basal
      phosphorylations in men and women, analysed separately. CONCLUSION: In summary,
      skeletal muscle basal AMPKalpha phosphorylation is higher in men compared to
      women, with no apparent effect on anaerobic performance.

PMID- 26305091
TI  - Genetic Diversity and mRNA Expression of Porcine MHC Class I Chain-Related 2 (SLA
      MIC2) Gene and Development of a High-Resolution Typing Method.
AB  - The genetic structure and function of MHC class I chain-related (MIC) genes in
      the pig genome have not been well characterized, and show discordance in
      available data. Therefore, we have experimentally characterized the exon-intron
      structure and functional copy expression pattern of the pig MIC gene, SLA-MIC2.
      We have also studied the genetic diversity of SLA-MIC2 from seven different
      breeds using a high-resolution genomic sequence-based typing (GSBT) method. Our
      results showed that the SLA-MIC2 gene has a similar molecular organization as the
      human and cattle orthologs, and is expressed in only a few tissues including the
      small intestine, lung, and heart. A total of fifteen SLA-MIC2 alleles were
      identified from typing 145 animals, ten of which were previously unreported. Our
      analysis showed that the previously reported and tentatively named SLA-MIC2*05,
      07, and 01 alleles occurred most frequently. The observed heterozygosity varied
      from 0.26 to 0.73 among breeds. The number of alleles of the SLA-MIC2 gene in
      pigs is somewhat lower compared to the number of alleles of the porcine MHC class
      I and II genes; however, the level of heterozygosity was similar. Our results
      indicate the comprehensiveness of using genomic DNA-based typing for the systemic
      study of the SLA-MIC2 gene. The method developed for this study, as well as the
      detailed information that was obtained, could serve as fundamental tools for
      understanding the influence of the SLA-MIC2 gene on porcine immune responses. 

PMID- 26305092
TI  - Prognostic Role of Functional Neuroimaging after Multilobar Resection in Patients
      with Localization-Related Epilepsy.
AB  - To investigate the usage of functional neuroimaging as a prognostic tool for
      seizure recurrence and long-term outcomes in patients with multilobar resection,
      we recruited 90 patients who received multilobar resections between 1995 and 2013
      with at least 1-year follow-up (mean 8.0 years). All patients were monitored
      using intracranial electroencephalography (EEG) after pre-surgical evaluation.
      Clinical data (demographics, electrophysiology, and neuroimaging) were reviewed
      retrospectively. Surgical outcomes were evaluated at 1, 2, 5 years after surgery,
      and at the end of the study. After 1 year, 56 patients (62.2%) became Engel class
      I and at the last follow-up, 47 patients (52.2%) remained seizure-free.
      Furthermore, non-localized 18F-fluorodeoxyglucose positron emission tomography
      (PET), identifying hypometabolic areas not concordant with ictal onset zones,
      significantly correlated with seizure recurrence after 1 year. Non-lesional
      magnetic resonance imaging (MRI) and left-sided resection correlated with poor
      outcomes. In the last follow-up, non-localized PET and left-sided resection
      significantly correlated with seizure recurrence. Both localized PET and ictal
      interictal SPECT subtraction co-registered to MR (SISCOM) predicted good surgical
      outcomes in the last follow-up (69.2%, Engel I). This study suggests that PET and
      SISCOM may predict postoperative outcomes for patients after multilobar epilepsy
      and shows comparable long-term surgical outcomes after multilobar resection. 

PMID- 26305093
TI  - Optimal Route for Human Umbilical Cord Blood-Derived Mesenchymal Stem Cell
      Transplantation to Protect Against Neonatal Hyperoxic Lung Injury: Gene
      Expression Profiles and Histopathology.
AB  - The aim of this study was to determine the optimal route of mesenchymal stem cell
      (MSC) transplantation. To this end, gene expression profiling was performed to
      compare the effects of intratracheal (i.t.) versus intravenous (i.v.) MSC
      administration. Furthermore, the therapeutic efficacy of each route to protect
      against neonatal hyperoxic lung injury was also determined. Newborn Sprague
      Dawley rats were exposed to hyperoxia (90% oxygen) from birth for 14 days. Human
      umbilical cord blood-derived MSCs labeling with PKH26 were transplanted through
      either the i.t. (5*10(5)) or i.v. (2*10(6)) route at postnatal day (P) 5. At P14,
      lungs were harvested for histological, biochemical and microarray analyses.
      Hyperoxic conditions induced an increase in the mean linear intercept and mean
      alveolar volume (MAV), indicative of impaired alveolarization. The number of ED-1
      positive cells was significantly decreased by both i.t. and i.v.
      transplantations. However, i.t. administration of MSCs resulted in a greater
      decrease in MAV and ED-1 positive cells compared to i.v. administration.
      Moreover, the number of TUNEL-positive cells was significantly decreased in the
      i.t. group, but not in the i.v. group. Although the i.t. group received only one
      fourth of the number of MSCs that the i.v. group did, a significantly higher
      number of donor cell-derived red PKH 26 positivity were recovered in the i.t.
      group. Hyperoxic conditions induced the up regulation of genes associated with
      the inflammatory response, such as macrophage inflammatory protein-1 alpha, tumor
      necrosis factor-alpha and inter leukin-6; genes associated with cell death, such
      as p53 and caspases; and genes associated with fibrosis, such as connective
      tissue growth factor. In contrast, hyperoxic conditions induced the dwon
      regulation of vascular endothelial growth factor and hepatocyte growth factor.
      These hyperoxia-induced changes in gene expression were decreased in the i.t.
      group, but not in the i.v. group. Thus, local i.t. MSC transplantation was more
      effective than systemic i.v. MSC administration in protecting against neonatal
      hyperoxic lung injury.

PMID- 26305094
TI  - 4EBP1 Is Dephosphorylated by Respiratory Syncytial Virus Infection.
AB  - Respiratory syncytial virus (RSV) requires protein biosynthesis machinery to
      generate progeny. There is evidence that RSV might alter some translation
      components since stress granules are formed in their host cells. Consistent with
      these observations, we found that RSV induces dephosphorylation of 4EBP1 (eIF4E
      binding protein), an important cellular translation factor. Our results show no
      correlation between the 4EBP1 dephosphorylation time and the decrease in the
      global rate of protein synthesis. Interestingly, treatment with rapamycin
      stimulates virus generation. The results suggest that RSV is a virus that still
      contains unknown mechanisms involved in the translation of their mRNAs through
      the alteration or modification of some translation factors, such as 4EBP1,
      possibly to favor its replicative cycle. 

PMID- 26305095
TI  - Frequency and Circadian Timing of Eating May Influence Biomarkers of Inflammation
      and Insulin Resistance Associated with Breast Cancer Risk.
AB  - Emerging evidence suggests that there is interplay between the frequency and
      circadian timing of eating and metabolic health. We examined the associations of
      eating frequency and timing with metabolic and inflammatory biomarkers putatively
      associated with breast cancer risk in women participating in the National Health
      and Nutrition Examination 2009-2010 Survey. Eating frequency and timing variables
      were calculated from 24-hour food records and included (1) proportion of calories
      consumed in the evening (5 pm-midnight), (2) number of eating episodes per day,
      and (3) nighttime fasting duration. Linear regression models examined each eating
      frequency and timing exposure variable with C-reactive protein (CRP)
      concentrations and the Homeostatic Model Assessment of Insulin Resistance (HOMA
      IR). Each 10 percent increase in the proportion of calories consumed in the
      evening was associated with a 3 percent increase in CRP. Conversely, eating one
      additional meal or snack per day was associated with an 8 percent reduction in
      CRP. There was a significant interaction between proportion of calories consumed
      in the evening and fasting duration with CRP (p = 0.02). A longer nighttime
      fasting duration was associated with an 8 percent lower CRP only among women who
      ate less than 30% of their total daily calories in the evening (p = 0.01). None
      of the eating frequency and timing variables were significantly associated with
      HOMA-IR. These findings suggest that eating more frequently, reducing evening
      energy intake, and fasting for longer nightly intervals may lower systemic
      inflammation and subsequently reduce breast cancer risk. Randomized trials are
      needed to validate these associations.

PMID- 26305096
TI  - Abnormal Localization of STK17A in Bile Canaliculi in Liver Allografts: An Early
      Sign of Chronic Rejection.
AB  - The biological significance of STK17A, a serine/threonine kinase, in the liver is
      not known. We analyzed STK17A expression in HepG2 cells and human liver tissue.
      Accordingly, we investigated whether STK17A could help in identifying earlier
      changes during the evolution of chronic rejection (CR) after liver
      transplantation. RT-PCR and immunofluorescence were used to analyze STK17A
      expression in HepG2 cells. Antibody microarray was performed using human liver
      samples from CR and healthy donors. Immunohistochemistry was used to verify the
      clinical utility of STK17A on sequential biopsies for the subsequent development
      of CR. A novel short isoform of STK17A was found in HepG2 cells. STK17A was
      localized in the nuclei and bile canaliculi in HepG2 cells and human livers.
      Microarray of STK17A revealed its decrease in failed liver allografts by CR.
      During the evolution of CR, the staining pattern of bile canalicular STK17A
      gradually changed from diffuse linear to focal intermittent. The focal
      intermittent staining pattern was observed before the definite diagnosis of CR.
      In conclusion, the present study was the first to find localization of STK17A in
      normal bile canaliculi. Abnormal expression and localization of STK17A were
      associated with CR of liver allografts since the early stage of the rejection
      process. 

PMID- 26305097
TI  - Undesirable Choice Biases with Small Differences in the Spatial Structure of
      Chance Stimulus Sequences.
AB  - In two-alternative discrimination tasks, experimenters usually randomize the
      location of the rewarded stimulus so that systematic behavior with respect to
      irrelevant stimuli can only produce chance performance on the learning curves.
      One way to achieve this is to use random numbers derived from a discrete binomial
      distribution to create a 'full random training schedule' (FRS). When using FRS,
      however, sporadic but long laterally-biased training sequences occur by chance
      and such 'input biases' are thought to promote the generation of laterally-biased
      choices (i.e., 'output biases'). As an alternative, a 'Gellerman-like training
      schedule' (GLS) can be used. It removes most input biases by prohibiting the
      reward from appearing on the same location for more than three consecutive
      trials. The sequence of past rewards obtained from choosing a particular
      discriminative stimulus influences the probability of choosing that same stimulus
      on subsequent trials. Assuming that the long-term average ratio of choices
      matches the long-term average ratio of reinforcers, we hypothesized that a
      reduced amount of input biases in GLS compared to FRS should lead to a reduced
      production of output biases. We compared the choice patterns produced by a
      'Rational Decision Maker' (RDM) in response to computer-generated FRS and GLS
      training sequences. To create a virtual RDM, we implemented an algorithm that
      generated choices based on past rewards. Our simulations revealed that, although
      the GLS presented fewer input biases than the FRS, the virtual RDM produced more
      output biases with GLS than with FRS under a variety of test conditions. Our
      results reveal that the statistical and temporal properties of training sequences
      interacted with the RDM to influence the production of output biases. Thus,
      discrete changes in the training paradigms did not translate linearly into
      modifications in the pattern of choices generated by a RDM. Virtual RDMs could be
      further employed to guide the selection of proper training schedules for
      perceptual decision-making studies. 

PMID- 26305098
TI  - The Prevalence of Anatomical Variations of the Median Nerve in the Carpal Tunnel:
      A Systematic Review and Meta-Analysis.
AB  - BACKGROUND AND OBJECTIVE: The course and branches of the median nerve (MN) in the
      wrist vary widely among the population. Due to significant differences in the
      reported prevalence of such variations, extensive knowledge on the anatomy of the
      MN is essential to avoid iatrogenic nerve injury. Our aim was to determine the
      prevalence rates of anatomical variations of the MN in the carpal tunnel and the
      most common course patterns and variations in its thenar motor branch (TMB).
      STUDY DESIGN: A systematic search of all major databases was performed to
      identify articles that studied the prevalence of MN variations in the carpal
      tunnel and the TMB. No date or language restrictions were set. Extracted data was
      classified according to Lanz's classification system: variations in the course of
      the single TMB--extraligamentous, subligamentous, and transligamentous (type 1);
      accessory branches of the MN at the distal carpal tunnel (type 2); high division
      of the MN (type 3); and the MN and its accessory branches proximal to the carpal
      tunnel (type 4). Pooled prevalence rates were calculated using MetaXL 2.0.
      RESULTS: Thirty-one studies (n = 3918 hands) were included in the meta-analysis.
      The pooled prevalence rates of the extraligamentous, subligamentous, and
      transligamentous courses were 75.2% (95%CI:55.4%-84.7%), 13.5% (95%CI:3.6%
      25.7%), and 11.3% (95%CI:2.4%-23.0%), respectively. The prevalence of Lanz group
      2, 3, and 4 were 4.6% (95%CI:1.6%-9.1%), 2.6% (95%CI:0.1%-2.8%), and 2.3%
      (95%CI:0.3%-5.6%), respectively. Ulnar side of branching of the TMB was found in
      2.1% (95%CI:0.9%-3.6%) of hands. The prevalence of hypertrophic thenar muscles
      over the transverse carpal ligament was 18.2% (95%CI:6.8%-33.0%). A
      transligamentous course of the TMB was more commonly found in hands with
      hypertrophic thenar muscles (23.4%, 95%CI:5.0%-43.4%) compared to those without
      hypertrophic musculature (1.7%, 95%CI:0%-100%). In four studies (n = 423 hands),
      identical bilateral course of the TMB was found in 72.3% (95%CI:58.4%-84.4%) of
      patients. CONCLUSIONS: Anatomical variations in the course of the TMB and the MN
      in the carpal tunnel are common in the population. Thus, we recommend an ulnar
      side approach to carpal tunnel release, with a careful layer by layer dissection,
      to avoid iatrogenic damage to the TMB.

PMID- 26305099
TI  - Transient laminin beta 1a Induction Defines the Wound Epidermis during Zebrafish
      Fin Regeneration.
AB  - The first critical stage in salamander or teleost appendage regeneration is
      creation of a specialized epidermis that instructs growth from underlying stump
      tissue. Here, we performed a forward genetic screen for mutations that impair
      this process in amputated zebrafish fins. Positional cloning and complementation
      assays identified a temperature-sensitive allele of the ECM component laminin
      beta 1a (lamb1a) that blocks fin regeneration. lamb1a, but not its paralog
      lamb1b, is sharply induced in a subset of epithelial cells after fin amputation,
      where it is required to establish and maintain a polarized basal epithelial cell
      layer. These events facilitate expression of the morphogenetic factors shha and
      lef1, basolateral positioning of phosphorylated Igf1r, patterning of new
      osteoblasts, and regeneration of bone. By contrast, lamb1a function is
      dispensable for juvenile body growth, homeostatic adult tissue maintenance,
      repair of split fins, or renewal of genetically ablated osteoblasts. fgf20a
      mutations or transgenic Fgf receptor inhibition disrupt lamb1a expression,
      linking a central growth factor to epithelial maturation during regeneration. Our
      findings reveal transient induction of lamb1a in epithelial cells as a key,
      growth factor-guided step in formation of a signaling-competent regeneration
      epidermis. 

PMID- 26305100
TI  - Type VI Secretion System Toxins Horizontally Shared between Marine Bacteria.
AB  - The type VI secretion system (T6SS) is a widespread protein secretion apparatus
      used by Gram-negative bacteria to deliver toxic effector proteins into adjacent
      bacterial or host cells. Here, we uncovered a role in interbacterial competition
      for the two T6SSs encoded by the marine pathogen Vibrio alginolyticus. Using
      comparative proteomics and genetics, we identified their effector repertoires. In
      addition to the previously described effector V12G01_02265, we identified three
      new effectors secreted by T6SS1, indicating that the T6SS1 secretes at least four
      antibacterial effectors, of which three are members of the MIX-effector class. We
      also showed that the T6SS2 secretes at least three antibacterial effectors. Our
      findings revealed that many MIX-effectors belonging to clan V are "orphan"
      effectors that neighbor mobile elements and are shared between marine bacteria
      via horizontal gene transfer. We demonstrated that a MIX V-effector from V.
      alginolyticus is a functional T6SS effector when ectopically expressed in another
      Vibrio species. We propose that mobile MIX V-effectors serve as an environmental
      reservoir of T6SS effectors that are shared and used to diversify antibacterial
      toxin repertoires in marine bacteria, resulting in enhanced competitive fitness. 

PMID- 26305101
TI  - Prospecting for Energy-Rich Renewable Raw Materials: Agave Leaf Case Study.
AB  - Plant biomass from different species is heterogeneous, and this diversity in
      composition can be mined to identify materials of value to fuel and chemical
      industries. Agave produces high yields of energy-rich biomass, and the sugar-rich
      stem tissue has traditionally been used to make alcoholic beverages. Here, the
      compositions of Agave americana and Agave tequilana leaves are determined,
      particularly in the context of bioethanol production. Agave leaf cell wall
      polysaccharide content was characterized by linkage analysis, non-cellulosic
      polysaccharides such as pectins were observed by immuno-microscopy, and leaf
      juice composition was determined by liquid chromatography. Agave leaves are fruit
      like--rich in moisture, soluble sugars and pectin. The dry leaf fiber was
      composed of crystalline cellulose (47-50% w/w) and non-cellulosic polysaccharides
      (16-22% w/w), and whole leaves were low in lignin (9-13% w/w). Of the dry mass of
      whole Agave leaves, 85-95% consisted of soluble sugars, cellulose, non-cellulosic
      polysaccharides, lignin, acetate, protein and minerals. Juice pressed from the
      Agave leaves accounted for 69% of the fresh weight and was rich in glucose and
      fructose. Hydrolysis of the fructan oligosaccharides doubled the amount of
      fermentable fructose in A. tequilana leaf juice samples and the concentration of
      fermentable hexose sugars was 41-48 g/L. In agricultural production systems such
      as the tequila making, Agave leaves are discarded as waste. Theoretically, up to
      4000 L/ha/yr of bioethanol could be produced from juice extracted from waste
      Agave leaves. Using standard Saccharomyces cerevisiae strains to ferment Agave
      juice, we observed ethanol yields that were 66% of the theoretical yields. These
      data indicate that Agave could rival currently used bioethanol feedstocks,
      particularly if the fermentation organisms and conditions were adapted to suit
      Agave leaf composition.

PMID- 26305104
TI  - Examining Nurse Consultant connectivity: An Australian mixed method study.
AB  - The nurse consultant (NC) role in Australia is a senior classification of
      advanced practice nurse has been described as enhancing health care outcomes
      largely through extensive collaboration with consumers, nurses, and other health
      professionals. However, little is known about the actual nature, amount, and
      quality of NC interactions. This study examines the connectivity of the NC role
      across metropolitan and rural contexts, using a mixed method sequential design
      with an online survey and focus groups with NCs and other stakeholders. Results
      demonstrated that NCs most commonly have high density connectivity patterns with
      other nursing colleagues, medical staff, patients/clients, and administrative
      staff. Position grade (1, 2 or 3) influences density of connectivity, as does
      location, with those based in metropolitan roles engaging significantly less with
      other clinicians. Findings demonstrate that many NCs are highly collaborative and
      predominantly embedded into interprofessional practice models. This study
      provides valuable insight into the diverse and often complex NC role and the way
      in which NC expertise and influence is deployed and integrated across a large
      local health district. 

PMID- 26305102
TI  - The UVB-Stimulated Expression of Transglutaminase 1 Is Mediated Predominantly via
      the NFkappaB Signaling Pathway: New Evidence of Its Significant Attenuation
      through the Specific Interruption of the p38/MSK1/NFkappaBp65 Ser276 Axis.
AB  - The influence of ultraviolet B (UVB) radiation on transglutaminase 1 (TGase 1), a
      major factor that regulates skin keratinization, has not been sufficiently
      characterized especially at the gene or protein level. Thus, we determined
      whether UVB affects the expression of TGase 1 in human keratinocytes and
      clarified the intracellular stress signaling mechanism(s) involved. Exposure of
      human keratinocytes to UVB significantly up-regulated the expression of TGase 1
      at the gene and protein levels. Treatment with inhibitors of p38, MEK, JNK or
      NFkappaB significantly abolished the UVB-stimulated protein expression of TGase
      1. Treatment with astaxanthin immediately after UVB irradiation did not attenuate
      the increased phosphorylation of Ser536/Ser468NFkappaBp65, c-Jun, ATK-2 and CK2,
      and did not abrogate the increased or diminished protein levels of c-Jun/c-Fos or
      I-kappaBalpha, respectively. However, the same treatment with astaxanthin
      significantly abolished the UVB-stimulated expression of TGase 1 protein, which
      was accompanied by the attenuated phosphorylation of Thr565/Ser376/Ser360MSK1,
      Ser276NFkappaBp65 and Ser133CREB. The MSK1 inhibitor H89 significantly down
      regulated the increased protein expression of TGase 1 in UVB-exposed human
      keratinocytes, which was accompanied by an abrogating effect on the increased
      phosphorylation of Ser276NFkappaBp65 and Ser133CREB but not
      Thr565/Ser376/Ser360MSK1. Transfection of human keratinocytes with MSK1 siRNA
      suppressed the UVB-stimulated protein expression of TGase 1. These findings
      suggest that the UVB-stimulated expression of TGase 1 is mediated predominantly
      via the NFkappaB pathway and can be attenuated through a specific interruption of
      the p38/MSK1/NFkappaBp65Ser276 axis. 

PMID- 26305103
TI  - Vitamin D and Risk of Multiple Sclerosis: A Mendelian Randomization Study.
AB  - BACKGROUND: Observational studies have demonstrated an association between
      decreased vitamin D level and risk of multiple sclerosis (MS); however, it
      remains unclear whether this relationship is causal. We undertook a Mendelian
      randomization (MR) study to evaluate whether genetically lowered vitamin D level
      influences the risk of MS. METHODS AND FINDINGS: We identified single nucleotide
      polymorphisms (SNPs) associated with 25-hydroxyvitamin D (25OHD) level from
      SUNLIGHT, the largest (n = 33,996) genome-wide association study to date for
      vitamin D. Four SNPs were genome-wide significant for 25OHD level (p-values
      ranging from 6 * 10-10 to 2 * 10-109), and all four SNPs lay in, or near, genes
      strongly implicated in separate mechanisms influencing 25OHD. We then ascertained
      their effect on 25OHD level in 2,347 participants from a population-based cohort,
      the Canadian Multicentre Osteoporosis Study, and tested the extent to which the
      25OHD-decreasing alleles explained variation in 25OHD level. We found that the
      count of 25OHD-decreasing alleles across these four SNPs was strongly associated
      with lower 25OHD level (n = 2,347, F-test statistic = 49.7, p = 2.4 * 10-12).
      Next, we conducted an MR study to describe the effect of genetically lowered
      25OHD on the odds of MS in the International Multiple Sclerosis Genetics
      Consortium study, the largest genetic association study to date for MS (including
      up to 14,498 cases and 24,091 healthy controls). Alleles were weighted by their
      relative effect on 25OHD level, and sensitivity analyses were performed to test
      MR assumptions. MR analyses found that each genetically determined one-standard
      deviation decrease in log-transformed 25OHD level conferred a 2.0-fold increase
      in the odds of MS (95% CI: 1.7-2.5; p = 7.7 * 10-12; I2 = 63%, 95% CI: 0%-88%).
      This result persisted in sensitivity analyses excluding SNPs possibly influenced
      by population stratification or pleiotropy (odds ratio [OR] = 1.7, 95% CI: 1.3
      2.2; p = 2.3 * 10-5; I2 = 47%, 95% CI: 0%-85%) and including only SNPs involved
      in 25OHD synthesis or metabolism (ORsynthesis = 2.1, 95% CI: 1.6-2.6, p = 1 * 10
      9; ORmetabolism = 1.9, 95% CI: 1.3-2.7, p = 0.002). While these sensitivity
      analyses decreased the possibility that pleiotropy may have biased the results,
      residual pleiotropy is difficult to exclude entirely. CONCLUSIONS: A genetically
      lowered 25OHD level is strongly associated with increased susceptibility to MS.
      Whether vitamin D sufficiency can delay, or prevent, MS onset merits further
      investigation in long-term randomized controlled trials.

PMID- 26305105
TI  - Quantifying patterns of upper limb motor change following BTX-A injection in
      adult spasticity management.
AB  - OBJECTIVE: To evaluate the capacity of the Upper Limb Performance Analysis:
      Comparative Analysis of Performance-Motor (CAP-M) to quantify change in adults
      with focal spasticity following injection of Botulinum Toxin-A (BTX-A) as a focal
      treatment for positive Upper Motor Neuron (UMN) features. METHODS: Twenty-three
      adults with moderate-to-severe spasticity were assessed pre- and post-BTX-A
      injection using CAP-M. Post-hoc video analysis of three sub-tests from the Action
      Research Arm Test were analysed against expected movements for each task.
      RESULTS: Post-injection, spasticity as measured by Modified Ashworth and Tardieu
      Composite scores decreased significantly (p < 0.001). Grouped CAP-M data showed a
      significant reduction (z = 2.1-2.7, ES = 0.51-0.56) in positive UMN features,
      with 145 fewer Excessive movements recorded. In addition, 31 more Expected
      movements were demonstrated (z = 2.9, ES = 0.60), consistent with 'unmasking' of
      movements. CONCLUSION: CAP-M analysis revealed that BTX-A injection decreased
      unwanted movement almost 5-times more frequently than 'unmasking' hidden
      voluntary muscle activity during active simulated tasks. In this way, CAP-M was
      able to simultaneously assess positive and negative UMN features. This
      quantitative framework may have greater functional relevance than traditional uni
      dimensional, passive spasticity measures such as MAS and Tardieu Scale.

PMID- 26305107
TI  - Porphyrin Boxes: Rationally Designed Porous Organic Cages.
AB  - The porphyrin boxes (PB-1 and PB-2), which are rationally designed porous organic
      cages with a large cavity using well-defined and rigid 3-connected triangular and
      4-connected square shaped building units are reported. PB-1 has a cavity as large
      as 1.95 nm in diameter and shows high chemical stability in a broad pH range (4.8
      to 13) in aqueous media. The crystalline nature as well as cavity structure of
      the shape-persistent organic cage crystals were intact even after complete
      removal of guest molecules, leading to one of the highest surface areas (1370
      m(2) g(-1)) among the known porous organic molecular solids. The size of the
      cavities and windows of the porous organic cages can be modulated using different
      sized building units while maintaining the topology of the cages, as illustrated
      with PB-2. Interestingly, PB-2 crystals showed unusual N2 sorption isotherms as
      well as high selectivity for CO2 over N2 and CH4 (201 and 47.9, respectively at
      273 K at 1 bar).

PMID- 26305108
TI  - PASS Targets: Ligand-based multi-target computational system based on a public
      data and naive Bayes approach.
AB  - Estimation of interactions between drug-like compounds and drug targets is very
      important for drug discovery and toxicity assessment. Using data extracted from
      the 19th version of the ChEMBL database ( https://www.ebi.ac.uk/chembl ) as a
      training set and a Bayesian-like method realized in PASS software (
      http://www.way2drug.com/PASSOnline ), we developed a computational tool for the
      prediction of interactions between protein targets and drug-like compounds. After
      training, PASS Targets became able to predict interactions of drug-like compounds
      with 2507 protein targets from different organisms based on analysis of structure
      activity relationships for 589,107 different chemical compounds. The prediction
      accuracy, estimated as AUC ROC calculated by the leave-one-out cross-validation
      and 20-fold cross-validation procedures, was about 96%. Average AUC ROC value was
      about 90% for the external test set from approximately 700 known drugs
      interacting with 206 protein targets. 

PMID- 26305106
TI  - Radiant energy required for infrared neural stimulation.
AB  - Infrared neural stimulation (INS) has been proposed as an alternative method to
      electrical stimulation because of its spatial selective stimulation. Independent
      of the mechanism for INS, to translate the method into a device it is important
      to determine the energy for stimulation required at the target structure. Custom
      designed, flat and angle polished fibers, were used to deliver the photons. By
      rotating the angle polished fibers, the orientation of the radiation beam in the
      cochlea could be changed. INS-evoked compound action potentials and single unit
      responses in the central nucleus of the inferior colliculus (ICC) were recorded.
      X-ray computed tomography was used to determine the orientation of the optical
      fiber. Maximum responses were observed when the radiation beam was directed
      towards the spiral ganglion neurons (SGNs), whereas little responses were seen
      when the beam was directed towards the basilar membrane. The radiant exposure
      required at the SGNs to evoke compound action potentials (CAPs) or ICC responses
      was on average 18.9 +/- 12.2 or 10.3 +/- 4.9 mJ/cm(2), respectively. For cochlear
      INS it has been debated whether the radiation directly stimulates the SGNs or
      evokes a photoacoustic effect. The results support the view that a direct
      interaction between neurons and radiation dominates the response to INS. 

PMID- 26305110
TI  - Correction: Designing Psychological Treatments for Scalability: The PREMIUM
      Approach.

PMID- 26305109
TI  - Wiskott-Aldrich syndrome proteins in the nucleus: aWASH with possibilities.
AB  - Actin and proteins that regulate its dynamics or interactions have well
      established roles in the cytoplasm where they function as key components of the
      cytoskeleton to control diverse processes, including cellular infrastructure,
      cellular motility, cell signaling, and vesicle transport. Recent work has also
      uncovered roles for actin and its regulatory proteins in the nucleus, primarily
      in mechanisms governing gene expression. The Wiskott Aldrich Syndrome (WAS)
      family of proteins, comprising the WASP/N-WASP, SCAR/WAVE, WHAMM/JMY/WHAMY, and
      WASH subfamilies, function in the cytoplasm where they activate the Arp2/3
      complex to form branched actin filaments. WAS proteins are present in the nucleus
      and have been implicated as transcriptional regulators. We found that Drosophila
      Wash, in addition to transcriptional effects, is involved in global nuclear
      architecture. Here we summarize the regulation and function of nuclear WAS
      proteins, and highlight how our work with Wash expands the possibilities for the
      functions of these proteins in the nucleus. 

PMID- 26305111
TI  - The Butterflies of Barro Colorado Island, Panama: Local Extinction since the
      1930s.
AB  - Few data are available about the regional or local extinction of tropical
      butterfly species. When confirmed, local extinction was often due to the loss of
      host-plant species. We used published lists and recent monitoring programs to
      evaluate changes in butterfly composition on Barro Colorado Island (BCI, Panama)
      between an old (1923-1943) and a recent (1993-2013) period. Although 601
      butterfly species have been recorded from BCI during the 1923-2013 period, we
      estimate that 390 species are currently breeding on the island, including 34
      cryptic species, currently only known by their DNA Barcode Index Number. Twenty
      three butterfly species that were considered abundant during the old period could
      not be collected during the recent period, despite a much higher sampling effort
      in recent times. We consider these species locally extinct from BCI and they
      conservatively represent 6% of the estimated local pool of resident species.
      Extinct species represent distant phylogenetic branches and several families. The
      butterfly traits most likely to influence the probability of extinction were host
      growth form, wing size and host specificity, independently of the phylogenetic
      relationships among butterfly species. On BCI, most likely candidates for
      extinction were small hesperiids feeding on herbs (35% of extinct species).
      However, contrary to our working hypothesis, extinction of these species on BCI
      cannot be attributed to loss of host plants. In most cases these host plants
      remain extant, but they probably subsist at lower or more fragmented densities.
      Coupled with low dispersal power, this reduced availability of host plants has
      probably caused the local extinction of some butterfly species. Many more bird
      than butterfly species have been lost from BCI recently, confirming that small
      preserves may be far more effective at conserving invertebrates than vertebrates
      and, therefore, should not necessarily be neglected from a conservation
      viewpoint. 

PMID- 26305112
TI  - Three-Dimensional Cu Foam-Supported Single Crystalline Mesoporous Cu2O Nanothorn
      Arrays for Ultra-Highly Sensitive and Efficient Nonenzymatic Detection of
      Glucose.
AB  - Highly sensitive and efficient biosensors play a crucial role in clinical,
      environmental, industrial, and agricultural applications, and tremendous efforts
      have been dedicated to advanced electrode materials with superior electrochemical
      activities and low cost. Here, we report a three-dimensional binder-free Cu foam
      supported Cu2O nanothorn array electrode developed via facile electrochemistry.
      The nanothorns growing in situ along the specific direction of <011> have single
      crystalline features and a mesoporous surface. When being used as a potential
      biosensor for nonenzyme glucose detection, the hybrid electrode exhibits
      multistage linear detection ranges with ultrahigh sensitivities (maximum of 97.9
      mA mM(-1) cm(-2)) and an ultralow detection limit of 5 nM. Furthermore, the
      electrode presents outstanding selectivity and stability toward glucose
      detection. The distinguished performances endow this novel electrode with
      powerful reliability for analyzing human serum samples. These unprecedented
      sensing characteristics could be ascribed to the synergistic action of superior
      electrochemical catalytic activity of nanothorn arrays with dramatically enhanced
      surface area and intimate contact between the active material (Cu2O) and current
      collector (Cu foam), concurrently supplying good conductivity for electron/ion
      transport during glucose biosensing. Significantly, our findings could guide the
      fabrication of new metal oxide nanostructures with well-organized morphologies
      and unique properties as well as low materials cost. 

PMID- 26305113
TI  - Children Age 7 Complete Complex Gait and Postural Tasks Differently Than Adults
      Under Dual-Task Conditions.
AB  - Healthy children (7 years old) and adults (20 years old) completed a simultaneous
      balancing, reaching, and cognitive task while standing and during gait. Cognitive
      accuracy rate for children and adults was similar for both postures; however,
      response latency was greater for children than adults. While standing, trunk,
      upper arm, and forearm segments moved as individual segments in adults; however,
      articulated control of the upper arm and forearm in children was not evident.
      Adults and children showed evidence of articulated segmental control during gait.
      Absolute gait velocity (m/s) was significantly slower for children; however,
      there was no effect of age on step length. Children 7 years old can perform a
      simultaneous motor and cognitive task but their performance strategies do not yet
      match young adults.

PMID- 26305114
TI  - An experimental Investigation of the Impact of Personality Disorder Diagnosis on
      Clinicians: Can We See Past the Borderline?
AB  - BACKGROUND: There is concern that diagnostic labels for psychiatric disorders may
      invoke damaging stigma, stereotypes and misunderstanding. AIMS: This study
      investigated clinicians' reactions to diagnostic labelling by examining their
      positive and negative reactions to the label borderline personality disorder
      (BPD). METHOD: Mental health professionals (n = 265) viewed a videotape of a
      patient suffering from panic disorder and agoraphobia undergoing assessment.
      Prior to viewing the videotape, participants were randomly allocated to one of
      three conditions and were given the following information about the patient: (a)
      general background information; (b) additional descriptive information about
      behaviour corresponding to BPD; and (c) additional descriptive information about
      behaviour corresponding to BPD, but explicitly adding BPD as a possible comorbid
      diagnostic label. All participants were then asked to note things they had seen
      in the videotape that made them feel optimistic or pessimistic about treatment
      outcome. RESULTS: Participants in the group that were explicitly informed that
      the patient had a BPD diagnostic label reported significantly fewer reasons to be
      optimistic than the other two groups. CONCLUSIONS: Diagnostic labels may
      negatively impact on clinicians' judgments and perceptions of individuals and
      therefore clinicians should think carefully about whether, and how, they use
      diagnoses and efforts should be made to destigmatize diagnostic terms.

PMID- 26305115
TI  - Corollary Discharge Failure in an Oculomotor Task Is Related to Delusional
      Ideation in Healthy Individuals.
AB  - Predicting the sensory consequences of saccadic eye movements likely plays a
      crucial role in planning sequences of saccades and in maintaining visual
      stability despite saccade-caused retinal displacements. Deficits in predictive
      activity, such as that afforded by a corollary discharge signal, have been
      reported in patients with schizophrenia, and may lead to the emergence of
      positive symptoms, in particular delusions of control and auditory
      hallucinations. We examined whether a measure of delusional thinking in the
      general, non-clinical population correlated with measures of predictive activity
      in two oculomotor tasks. The double-step task measured predictive activity in
      motor control, and the in-flight displacement task measured predictive activity
      in trans-saccadic visual perception. Forty-one healthy adults performed both
      tasks and completed a questionnaire to assess delusional thinking. The
      quantitative measure of predictive activity we obtained correlated with the
      tendency towards delusional ideation, but only for the motor task, and not the
      perceptual task: Individuals with higher levels of delusional thinking showed
      less self-movement information use in the motor task. Variation of the degree of
      self-generated movement knowledge as a function of the prevalence of delusional
      ideation in the normal population strongly supports the idea that corollary
      discharge deficits measured in schizophrenic patients in previous researches are
      not due to neuroleptic medication. We also propose that this difference in
      results between the perceptual and the motor tasks may point to a dissociation
      between corollary discharge for perception and corollary discharge for action. 

PMID- 26305116
TI  - Metformin inhibits proliferation and proinflammatory cytokines of human
      keratinocytes in vitro via mTOR-signaling pathway.
AB  - CONTEXT: The antidiabetic drug metformin exhibits antiproliferative and pro
      apoptotic effects in various cells, suggesting its potential to treat a variety
      of malignant and non-malignant hyperplastic diseases. Clinical studies indicate
      that psoriasis patients with metformin treatment have a better response than
      those without metformin. OBJECTIVE: The present study evaluates the
      antiproliferative activity and anti-inflammatory responses of metformin in human
      keratinocytes in vitro and explores the underlying mechanisms. MATERIALS AND
      METHODS: HaCaT cells were incubated with metformin at 0, 25, 50, and 100 mM for
      48 h. Antiproliferative activity was evaluated by MTT and apoptotic response was
      examined by flow cytometry. ELISA was used to detect IL-6, TNF-alpha, and VEGF
      protein expression. Western blot was used to investigate the expression of the
      mammalian target of rapamycin (mTOR) and its downstream effectors p70 ribosomal
      S6 kinase (p70S6K). RESULTS: The survival rates of HaCaT cells treated with
      metformin at 50 mM were reduced to 75.6, 59.4, and 30.3% at 24, 48, and 72 h,
      respectively. The number of apoptotic HaCaT cells was significantly increased at
      50 mM metformin after 48 h treatment. Metformin can exert an anti-inflammatory
      effect by direct inhibition of IL-6, TNF-alpha, and VEGF. Metformin at 50 mM
      significantly reduced the phosphorylation of mTOR and p70S6K, by 49.0 and 62.1%,
      respectively. DISCUSSION AND CONCLUSION: Metformin treatment significantly
      inhibited proliferation and proinflammatory responses in HaCaT cells by a
      mechanism associated with inhibition of the mTOR signaling pathway. The results
      indicate that metformin may be used as a potential therapeutic agent for
      psoriasis.

PMID- 26305117
TI  - 3D Topography of the Young Adult Anal Sphincter Complex Reconstructed from
      Undeformed Serial Anatomical Sections.
AB  - BACKGROUND: Pelvic-floor anatomy is usually studied by artifact-prone dissection
      or imaging, which requires prior anatomical knowledge. We used the serial-section
      approach to settle contentious issues and an interactive 3D-pdf to make the
      results widely accessible. METHOD: 3D reconstructions of undeformed thin serial
      anatomical sections of 4 females and 2 males (21-35y) of the Chinese Visible
      Human database. FINDINGS: Based on tendinous septa and muscle-fiber orientation
      as segmentation guides, the anal-sphincter complex (ASC) comprised the
      subcutaneous external anal sphincter (EAS) and the U-shaped puborectal muscle, a
      part of the levator ani muscle (LAM). The anococcygeal ligament fixed the EAS to
      the coccygeal bone. The puborectal-muscle loops, which define the levator hiatus,
      passed around the anorectal junction and inserted anteriorly on the perineal body
      and pubic bone. The LAM had a common anterior attachment to the pubic bone, but
      separated posteriorly into puborectal and "pubovisceral" muscles. This
      pubovisceral muscle was bilayered: its internal layer attached to the conjoint
      longitudinal muscle of the rectum and the rectococcygeal fascia, while its outer,
      patchy layer reinforced the inner layer. ASC contraction makes the ano-rectal
      bend more acute and lifts the pelvic floor. Extensions of the rectal longitudinal
      smooth muscle to the coccygeal bone (rectococcygeal muscle), perineal body
      (rectoperineal muscle), and endopelvic fascia (conjoint longitudinal and
      pubovisceral muscles) formed a "diaphragm" at the inferior boundary of the
      mesorectum that suspended the anorectal junction. Its contraction should
      straighten the anorectal bend. CONCLUSION: The serial-section approach settled
      contentious topographic issues of the pelvic floor. We propose that the ASC is
      involved in continence and the rectal diaphragm in defecation.

PMID- 26305118
TI  - Scent of a Dragonfly: Sex Recognition in a Polymorphic Coenagrionid.
AB  - In polymorphic damselflies discrimination of females from males is complex owing
      to the presence of androchrome and gynochrome females. To date there is no
      evidence that damselflies use sensory modalities other than vision (and tactile
      stimuli) in mate searching and sex recognition. The results of the present
      behavioural and electrophysiological investigations on Ischnura elegans, a
      polymorphic damselfly, support our hypothesis that chemical cues could be
      involved in Odonata sex recognition. The bioassays demonstrate that males in
      laboratory prefer female to male odour, while no significant difference was
      present in male behavior between stimuli from males and control. The bioassays
      suggest also some ability of males to distinguish between the two female morphs
      using chemical stimuli. The ability of male antennae to perceive odours from
      females has been confirmed by electrophysiological recordings. These findings are
      important not only to get insight into the chemical ecology of Odonata, and to
      shed light into the problem of olfaction in Paleoptera, but could be useful to
      clarify the controversial aspects of the mating behavior of polymorphic
      coenagrionids. Behavioural studies in the field are necessary to investigate
      further these aspects. 

PMID- 26305119
TI  - Peroxisome biogenesis in mammalian cells: The impact of genes and environment.
AB  - The initiation and progression of many human diseases are mediated by a complex
      interplay of genetic, epigenetic, and environmental factors. As all diseases
      begin with an imbalance at the cellular level, it is essential to understand how
      various types of molecular aberrations, metabolic changes, and environmental
      stressors function as switching points in essential communication networks. In
      recent years, peroxisomes have emerged as important intracellular hubs for redox
      , lipid-, inflammatory-, and nucleic acid-mediated signaling pathways. In this
      review, we focus on how nature and nurture modulate peroxisome biogenesis and
      function in mammalian cells. First, we review emerging evidence that changes in
      peroxisome activity can be linked to the epigenetic regulation of cell function.
      Next, we outline how defects in peroxisome biogenesis may directly impact
      cellular pathways involved in the development of disease. In addition, we discuss
      how changes in the cellular microenvironment can modulate peroxisome biogenesis
      and function. Finally, given the importance of peroxisome function in multiple
      aspects of health, disease, and aging, we highlight the need for more research in
      this still understudied field.

PMID- 26305121
TI  - Delivery of institutional long-term care under two social insurances: Lessons
      from the Korean experience.
AB  - Little is known about health and social care provision for people with long-term
      care (LTC) needs under multiple insurances. The aim of this study is to compare
      the profile, case-mix, and service provision to older people at long-term care
      hospitals (LTCHs) covered by the national health insurance (NHI) with those of
      older people at long-term care facilities (LTCFs) covered by the public long-term
      care insurance (LTCI) in Korea. A national LTC survey using common functional
      measures and a case-mix classification system was conducted with a nationally
      representative sample of older people at LTCFs and LTCHs in 2013. The majority of
      older people in both settings were female and frail, with complex chronic
      diseases. About one fourth were a low-income population with Medical-Aid. The key
      functional status was similar between the two groups. As for case-mix, more than
      half of the LTCH population were categorized as having lower medical care needs,
      while more than one fourth of the LTCF residents had moderate or higher medical
      care needs. Those with high medical care needs at LTCFs were significantly more
      likely to be admitted to acute-care hospitals than their counterparts at LTCHs.
      The current delivery of institutional LTC under the two insurances in Korea is
      not coordinated well. It is necessary to redefine the roles of LTCHs and
      strengthen health care in LTCFs. A systems approach is critical to establish
      person-centered, integrated LTC delivery across different financial sources. 

PMID- 26305122
TI  - Fabrication of High-Q Nanobeam Photonic Crystals in Epitaxially Grown 4H-SiC.
AB  - Silicon carbide (SiC) is an intriguing material due to the presence of spin
      active point defects in several polytypes, including 4H-SiC. For many quantum
      information and sensing applications involving such point defects, it is
      important to couple their emission to high quality optical cavities. Here we
      present the fabrication of 1D nanobeam photonic crystal cavities (PCC) in 4H-SiC
      using a dopant-selective etch to undercut a homoepitaxially grown epilayer of p
      type 4H-SiC. These are the first PCCs demonstrated in 4H-SiC and show high
      quality factors (Q) of up to ~7000 as well as low modal volumes of <0.5
      (lambda/n)(3). We take advantage of the high device yield of this fabrication
      method to characterize hundreds of devices and determine which PCC geometries are
      optimal. Additionally, we demonstrate two methods to tune the resonant
      wavelengths of the PCCs over 5 nm without significant degradation of the Q.
      Lastly, we characterize nanobeam PCCs coupled to luminescence from silicon
      vacancy point defects (V1, V2) in 4H-SiC. The fundamental modes of two such PCCs
      are tuned into spectral overlap with the zero phonon line (ZPL) of the V2 center,
      resulting in an intensity increase of up to 3-fold. These results are important
      steps on the path to developing 4H-SiC as a platform for quantum information and
      sensing. 

PMID- 26305120
TI  - Mitochondrial DNA has a pro-inflammatory role in AMD.
AB  - Age-related macular degeneration (AMD) is the leading cause of irreversible
      blindness in the elderly of industrialized nations, and there is increasing
      evidence to support a role for chronic inflammation in its pathogenesis.
      Mitochondrial DNA (mtDNA) has been recently reported to be pro-inflammatory in
      various diseases such as Alzheimer's and heart failure. Here, we report that
      intracellular mtDNA induces ARPE-19 cells to secrete inflammatory cytokines IL-6
      and IL-8, which have been consistently associated with AMD onset and progression.
      The induction was dependent on the size of mtDNA, but not on specific sequence.
      Oxidative stress plays a major role in the development of AMD, and our findings
      indicate that mtDNA induces IL-6 and IL-8 more potently when oxidized. Cytokine
      induction was mediated by STING (Stimulator of Interferon Genes) and NF-kappaB as
      evidenced by abrogation of the cytokine response with the use of specific
      inhibitors (siRNA and BAY 11-7082, respectively). Finally, mtDNA primed the NLRP3
      inflammasome. This study contributes to our understanding of the potential pro
      inflammatory role of mtDNA in the pathogenesis of AMD. 

PMID- 26305123
TI  - Comment on "Enhanced Long-Term Nitrogen Removal and Its Quantitative Molecular
      Mechanism in Tidal Flow Constructed Wetlands".

PMID- 26305124
TI  - Movement decoding using neural synchronization and inter-hemispheric connectivity
      from deep brain local field potentials.
AB  - OBJECTIVE: Correlating electrical activity within the human brain to movement is
      essential for developing and refining interventions (e.g. deep brain stimulation
      (DBS)) to treat central nervous system disorders. It also serves as a basis for
      next generation brain-machine interfaces (BMIs). This study highlights a new
      decoding strategy for capturing movement and its corresponding laterality from
      deep brain local field potentials (LFPs). APPROACH: LFPs were recorded with
      surgically implanted electrodes from the subthalamic nucleus or globus pallidus
      interna in twelve patients with Parkinson's disease or dystonia during a visually
      cued finger-clicking task. We introduce a method to extract frequency dependent
      neural synchronization and inter-hemispheric connectivity features based upon
      wavelet packet transform (WPT) and Granger causality approaches. A novel weighted
      sequential feature selection algorithm has been developed to select optimal
      feature subsets through a feature contribution measure. This is particularly
      useful when faced with limited trials of high dimensionality data as it enables
      estimation of feature importance during the decoding process. MAIN RESULTS: This
      novel approach was able to accurately and informatively decode movement related
      behaviours from the recorded LFP activity. An average accuracy of 99.8% was
      achieved for movement identification, whilst subsequent laterality classification
      was 81.5%. Feature contribution analysis highlighted stronger contralateral
      causal driving between the basal ganglia hemispheres compared to ipsilateral
      driving, with causality measures considerably improving laterality
      discrimination. SIGNIFICANCE: These findings demonstrate optimally selected
      neural synchronization alongside causality measures related to inter-hemispheric
      connectivity can provide an effective control signal for augmenting adaptive
      BMIs. In the case of DBS patients, acquiring such signals requires no additional
      surgery whilst providing a relatively stable and computationally inexpensive
      control signal. This has the potential to extend invasive BMI, based on
      recordings within the motor cortex, by providing additional information from
      subcortical regions.

PMID- 26305125
TI  - Synthesis and Structure-Activity Relationships of Tambjamines and B-Ring
      Functionalized Prodiginines as Potent Antimalarials.
AB  - Synthesis and antimalarial activity of 94 novel bipyrrole tambjamines (TAs) and a
      library of B-ring functionalized tripyrrole prodiginines (PGs) against a panel of
      Plasmodium falciparum strains are described. The activity and structure-activity
      relationships demonstrate that the ring-C of PGs can be replaced by an
      alkylamine, providing for TAs with retained/enhanced potency. Furthermore, ring-B
      of PGs/TAs can be substituted with short alkyl substitutions at either 4-position
      (replacement of OMe) or 3- and 4-positions without impacting potency. Eight
      representative TAs and two PGs have been evaluated for antimalarial activity
      against multidrug-resistant P. yoelii in mice in the dose range of 5-100 mg/kg *
      4 days by oral administration. The KAR425 TA offered greater efficacy than
      previously observed for any PG, providing 100% protection to malaria-infected
      mice until day 28 at doses of 25 and 50 mg/kg * 4 days, and was also curative in
      this model in a single oral dose (80 mg/kg). This study presents the first
      account of antimalarial activity in tambjamines. 

PMID- 26305126
TI  - Falls in Palliative Care.

PMID- 26305127
TI  - Foreword to the Special Issue: Rediscovering Jay Haley's Contributions to
      Hypnosis.

PMID- 26305128
TI  - Comment on the Special Issue: Jay Douglas Haley.

PMID- 26305129
TI  - Explorer in Hypnosis.
AB  - Written in 1957, this paper was Jay Haley's first attempt to organize his
      impressions of Milton Erickson. The article captures the essence of Erickson: the
      man, his early concepts of the trance state, his flexibility in trance induction,
      and his delight in working with those considered "resistant subjects." In this
      early paper, Jay Haley clearly recognizes Erickson's potential impact on therapy
      and clinicians around the world. This paper reminds readers of the importance of
      therapeutic relationship and the power of effective communication. 

PMID- 26305130
TI  - Discussions on Hypnosis and Schizophrenia.
AB  - A classic paper in intellect and argument, this article contains a transcript of
      a conversation between Jay Haley, John Weakland, and Milton Erickson as they
      discuss the role of communication in hypnosis and schizophrenia. In 1955,
      schizophrenia was considered primarily a psychological disorder. Whereas today
      schizophrenia is mostly considered a biological disorder, this very early,
      unpublished paper still gives much food for thought and a further glimpse into
      Haley and Erickson's thinking and intellect at a fervent time in schizophrenia
      research. 

PMID- 26305131
TI  - An Interactional Explanation of Hypnosis.
AB  - In this paper, the author offers what he sees as a new approach to understanding
      or defining hypnosis. Drawing from his work with Gregory Bateson, John Weakland,
      Don Jackson, and Bill Fry, Haley emphasizes the relational communicative aspect
      of trance. Noting the inherent difficulty of studying subjective experience,
      Haley highlights again the importance of communication and the therapist-patient
      relationship. 

PMID- 26305132
TI  - Jay Haley's Supervision of a Case of Dissociative.
AB  - This is a transcript of a supervision session with a young therapist caught in
      the complex world of a woman with multiple personality. Occurring very early in
      the written literature about treating multiple personalities, the highlight of
      this paper is the supervision style and technique of Jay Haley. His approach to
      supervision will make the reader wish that he or she could be in the room during
      this session. 

PMID- 26305133
TI  - Autohypnosis and Trance Dance in Bali.
AB  - A masterpiece of historical importance, this paper recounts Jay and Madeleine
      Haley's trip to Bali nearly 50 years after Gregory Bateson and Margaret Mead
      first went there. The Haleys met several of the same individuals who greeted
      Bateson and Mead and made a film they entitled "Dance and Trance of Balinese
      Children." This is a fascinating document of a culture and society so different
      from our own and the technique of dance and trance used to regulate emotion and
      violence. 

PMID- 26305134
TI  - Hypnotic Seminar.
AB  - In this transcription of a lecture given in 2000, Jay Haley begins by answering
      the question, "What is hypnosis?"  Haley reviews the circumstances of Gregory
      Bateson encouraging him to meet with Milton Erickson to discuss the history of
      hypnosis and the paradoxical nature of trance induction. Haley expresses many
      original thoughts about multiple personalities, regression to past lives, and how
      to handle memories that historically may be false. Sophisticated and subtle, this
      is Haley at his best. 

PMID- 26305135
TI  - Jay Haley: Books in English and Other Languages, and Films.

PMID- 26305137
TI  - Dynamic viscoelastic models of human skin using optical elastography.
AB  - A novel technique for measuring in vivo human skin viscoelastic properties using
      optical elastography has been developed. The technique uses geometrically focused
      surface (GFS) waves that allow for wide bandwidth measurements of the wave field.
      An analytical solution for the case of a radiating annular disk surface source
      was fit to experimentally measured GFS waves, enabling an estimate of the
      frequency-dependent surface wavenumber, which can then be related to the dynamic
      shear modulus. Several viscoelastic models were then fit to the dynamic shear
      modulus dispersion curve. Viscoelastic models were evaluated based on their
      overall quality of fit and variability amongst healthy volunteers. An Ecoflex
      phantom was used to validate the procedure and results by comparison to similar
      studies using the same type of phantom. For skin results, it was found that the
      'alpha' parameters from the fractional models had the least variability, with
      coefficients of variability of 0.15, and 0.16. The best fitting models were the
      standard linear solid, and the fractional Voigt, with a mean fit correlation
      coefficient, R(2), of 0.93, 0.89, respectively. This study has demonstrated the
      efficacy of this new method, and with larger studies the viscoelastic skin models
      could be used to identify various skin diseases and their response to treatment.

PMID- 26305138
TI  - [The human microbiome].
AB  - Research into the human microbiome will substantially enhance our understanding
      of inflammatory, metabolic and malignant diseases. The complexity of this
      research area can only be addressed by an interdisciplinary translational
      approach including bioinformatics. Data derived from pure in silico analyses and
      statistical associations will not automatically translate into sound clinical
      concepts, as we have learned previously in genetics. Potential targets for future
      treatment strategies include the proven impact of nutrition and medication on
      microbial diversity and therapeutic effects of microbial metabolic processes and
      metabolites. Fecal microbial transplantation (FMT) beyond its indication in
      refractory Clostridium difficile infection (CDI) should be held against the same
      standards and regulated by the same procedures that are applied to all
      investigational compounds and treatments prior to their approval. Donor fidelity,
      sample processing and recipient safety (including the role of fecal pathogens and
      toxins) need thorough scientific investigation and evaluation in clinical trials
      with objective outcome parameters prior to any recommendations for clinical
      practice. 

PMID- 26305139
TI  - Chelation therapy for treatment of systemic intoxication with uranium: A review.
AB  - Elevated levels of naturally occurring uranium have been found in small
      geographic areas throughout the world. Exposure of the general public to uranium
      is most often by the ingestion of food and water containing natural uranium from
      the hydrogeological environment, but this likelihood is remote. However, the risk
      is increased in regions where uranium is mined, milled, processed and/or
      fabricated as well as in the vicinity of former battlefields where depleted
      uranium munitions were deployed. Exposure in such cases is by the inhalation
      route. Internalized uranium is a long-term hazard the toxicity of which depends
      upon the dose and the dose rate as well as other parameters such as the chemical
      form and site of deposition of the uranium and the physiology of the host. The
      radiological toxicity and the chemical toxicity of uranium and its compounds are
      responsible for kidney damage and lung cancer. The vulnerable groups are the very
      young and the very old, individuals predisposed to hypertension or osteoporosis
      and individuals with chronic kidney disease. Those subject to long-term exposure
      from internalized uranium are a greater risk for the long-term implications. The
      accumulation of uranium may be mitigated by decreasing its absorption,
      distribution and deposition and increasing its elimination with chelating agents.
      The formation of soluble chelates may enhance the mobilization of uranium
      deposited in tissue and expedite its transport to and elimination from the renal
      system. The focus of this review is on the use of chelating agents to enhance
      decorporation of uranium thereby reducing the risk of intoxication. 

PMID- 26305140
TI  - [Tumors of dendritic and other accessory cells of lymph nodes].
AB  - Besides the obviously much more common lymphomas, neoplasms of dendritic and
      other so-called accessory cells can also primarily originate in lymph nodes.
      These include histiocytic sarcomas, follicular dendritic cell sarcomas,
      interdigitating dendritic cell sarcomas, fibroblastic reticulum cell
      tumors/cytokeratin-positive interstitial cell neoplasms and neoplasms of
      indeterminate dendritic cells. A feature common to all of these tumors is the
      very difficult differential diagnosis, not least because of their rarity;
      however, a careful analysis will allow discrimination from other sarcomas,
      sarcomatoid carcinomas, lymphomas and melanomas and lead to the correct
      classification of the respective lesions. From the pathogenetic view point it is
      interesting that there is an increased association of these tumors with lymphomas
      and leukemias. Moreover, many cases demonstrate shared clonal antigen receptor
      rearrangements and/or recurrent genetic aberrations in both histologically
      different tumor components. This suggests a common precursor cell or at least a
      common derivation. 

PMID- 26305142
TI  - [Erdheim-Chester disease and Rosai-Dorfman disease: Pathological, radiological
      and clinical features of adult non-Langerhans cell histiocytosis].
AB  - Non-Langerhans cell histiocytoses (N-LCH) of adulthood are rare disorders with
      heterogeneous pathogenesis, morphology and clinical presentation. In this review
      two disorders are presented, which predominantly develop in extracutaneous sites
      in adults. Erdheim-Chester disease is a rare nonhereditary clonal disorder of
      lipid storing histiocytes most commonly presenting as osseous involvement of the
      long bones. Other organ manifestations include the central nervous system (CNS),
      the cardiovascular system, the retroperitoneum and kidneys and less commonly the
      skin and the lungs. Immunohistochemical staining reveals positivity for the
      macrophage markers CD163, CD68 and lysozyme but CD1a and langerin are negative,
      in contrast to Langerhans cell histiocytosis. Rosai-Dorfman disease is considered
      to be a reactive histiocytic proliferation occurring mainly in lymph nodes.
      Prominent sinuses filled with commonly multinucleated, S100-positive histiocytes
      with emperipolesis are a characteristic feature and develops particularly as
      extensive lymphadenopathy with massive sinus histiocytosis but can also occur
      extranodally. Painless bilateral cervical lymph node enlargement is the most
      common clinical presentation. This review summarizes the clinical, radiological
      and histopathological findings and discusses the recent molecular advances in
      these rare disorders.

PMID- 26305143
TI  - Comparison of the efficacy and safety of tolterodine 2 mg and 4 mg combined with
      an alpha-blocker in men with lower urinary tract symptoms (LUTS) and overactive
      bladder: a randomized controlled trial.
AB  - OBJECTIVE: To evaluate the efficacy and safety of low-dose (2 mg) tolterodine
      extended release (ER) with an alpha-blocker compared with standard-dose (4 mg)
      tolterodine ER with an alpha-blocker for the treatment of men with residual
      storage symptoms after alpha-blocker monotherapy. PATIENTS AND METHODS: The study
      was a 12-week, single-blind, randomized, parallel-group, non-inferiority trial
      that included men with residual storage symptoms despite receiving at least 4
      weeks of alpha-blocker treatment. Inclusion criteria were total International
      Prostate Symptom Score (IPSS) >=12, IPSS quality-of-life item score >=3, and >=8
      micturitions and >=2 urgency episodes per 24 h. The primary outcome was change in
      the total IPSS score from baseline. Bladder diary variables, patient-reported
      outcomes and safety were also assessed. RESULTS: Patients were randomly assigned
      to addition of either 2 mg tolterodine ER (n = 47) or 4 mg tolterodine ER (n =
      48) to alpha-blocker therapy for 12 weeks. Patients in both treatment groups had
      a significant improvement in total IPSS score (-5.5 and -6.3, respectively),
      micturition per 24 h (-1.3 and -1.7, respectively) and nocturia per night (-0.4
      and -0.4, respectively). Changes in IPSS, bladder diary variables, and patient
      reported outcomes were not significantly different between the treatment groups.
      All interventions were well tolerated by patients. CONCLUSIONS: These results
      suggest that 12 weeks of low-dose tolterodine ER add-on therapy is similar to
      standard-dose tolterodine ER add-on therapy in terms of efficacy and safety for
      patients experiencing residual storage symptoms after receiving alpha-blocker
      monotherapy.

PMID- 26305144
TI  - Impacts of beta-estradiol on intestinal injury in newborn rats.
AB  - OBJECTIVE: Necrotizing enterocolitis has been investigated and debated
      extensively in recent years; however, there is still no effective treatment. The
      aim of this study was thus to examine the effects of beta-estradiol on intestinal
      injury in rats. METHODS: Twenty-four newborn female rat pups were divided into
      three groups. In group 1 (sham), hypoxia-re-oxygenation was not performed. In
      group 2 (saline), the rats were injected with saline after hypoxia-re
      oxygenation, and the process was repeated for 5 d. In group 3 (beta-estradiol
      treatment), the rats were subjected to hypoxia-re-oxygenation and then given beta
      estradiol intraperitoneally once a day for 5 d. After these procedures, the
      terminal ileum was removed for analysis. RESULTS: Statistically significant
      differences in histological grades were found between groups 1 and 2 (p = 0.000),
      groups 1 and 3 (p = 0.028), and groups 2 and 3 (p = 0.021). There were also
      differences in TNF-alpha and IL-6 levels between groups 2 and 3 (p = 0.000 and p
      = 0.038, respectively) and between groups 1 and 2 (p = 0.000 and p = 0.000);
      there was no difference between groups 1 and 3 (p = 0.574 and p = 0.195,
      respectively). Electron microscopy examination revealed a decrease in lipid
      droplets at the apical cytoplasm of the columnar cells in group 2; in group 3,
      the absorption of the lipids as lipid droplets was similar to that of group 1.
      CONCLUSION: In this study, beta-estradiol was found to decrease the intensity of
      intestinal injury significantly by inhibiting TNF-alpha and IL-6.

PMID- 26305145
TI  - A Simplified Diagnostic Observational Assessment of Autism Spectrum Disorder in
      Early Childhood.
AB  - Subspecialty physicians who have expertise in the diagnosis of autism spectrum
      disorder typically do not have the resources to administer comprehensive
      diagnostic observational assessments for patients suspected of ASD. The autism
      mental status exam (AMSE) is a free and brief eight-item observation tool that
      addresses this practice gap. The AMSE, designed by Child and Adolescent
      Psychiatrists, Developmental Behavioral Pediatricians and Pediatric Neurologists
      structures the observation and documentation of signs and symptoms of ASD and
      yields a score. Excellent sensitivity and specificity was demonstrated in a
      population of high-risk adults. This protocol now investigates the AMSE's test
      performance in a population of 45 young children age 18 months to 5 years with
      suspected ASD or social and communication concerns who are evaluated at an autism
      research center. Each subject received a developmental evaluation, including the
      AMSE, performed by a Child and Adolescent Psychiatrist, that was followed by
      independent standardized assessment using the Autism Diagnostic Observation
      Schedule and the Autism Diagnostic Interview-Revised. A Best Estimate Diagnosis
      protocol used DSM-5 criteria to ascertain a diagnosis of ASD or non-ASD. Receiver
      operating characteristic curve analysis was used to determine the AMSE cut point
      with the highest sensitivity and specificity. Findings indicate an optimized
      sensitivity of 94% and a specificity of 100% for this high prevalence group.
      Because of its high classification accuracy in this sample of children the AMSE
      holds promise as a tool that can support both diagnostic decision making and
      standardize point of care observational assessment of ASD in high risk children.

PMID- 26305146
TI  - Falling in love with romantic ideals: women in relationships with child
      molesters.
AB  - Drawing on data from a larger research study, this paper explores intersecting
      and competing social relations that influenced the romantic desires of women who
      became intimately involved with men who molested children. Through a feminist
      poststructuralist lens, women's narratives were analysed with the use of feminist
      interpretations of Foucauldian discourse theory. Analysis informed of a
      discursive power over participants that made the attainment of romantic desires
      an imperative for ensuring social respect, worth and credibility as women. When
      all was not ideal, these same romantic desires compelled women to fix and hold
      onto their relationships--even when with men that attract damning societal
      responses towards them. Even upon acknowledgement of their partners' sexual
      transgressions, the fear of relationship breakdown meant that romantic desires
      again featured as imperatives for the women. The imagined pleasure of achieving
      romantic desires is discursive; so powerful that it outweighed women's fears and
      dangers of precarious intimate life with men who commit abhorrent acts.

PMID- 26305147
TI  - Impact of Microscale and Pilot-Scale Freeze-Drying on Protein Secondary
      Structures: Sucrose Formulations of Lysozyme and Catalase.
AB  - Microscale (MS) freeze-drying offers rapid process cycles for early-stage
      formulation development. The effects of the MS approach on the secondary
      structures of two model proteins, lysozyme and catalase, were compared with pilot
      scale (PS) vial freeze-drying. The secondary structures were assessed by
      attenuated total reflection Fourier transformed infrared spectroscopy.
      Formulations were made with increasing sucrose-protein ratios. Freeze-drying
      protocols involved regular cooling without thermal treatment and annealing with
      MS and PS equipment, and cooling rate variations with the MS. Principal component
      analysis of smoothed second-derivative amide I spectra revealed sucrose-protein
      ratio-dependent shifts toward alpha-helical structures. Transferability of
      sucrose-protein formulations from MS to PS vial freeze-drying was evidenced at
      regular cooling rates. Local differences in protein secondary structures between
      the bottom and top of sucrose-catalase samples could be detected at the sucrose
      catalase ratios of 1 and 2, this being related to the initial filling height and
      ice crystal morphology. Annealing revealed temperature, protein, formulation, and
      sample location-dependent effects influencing surface morphology at the top, or
      causing protein secondary structure perturbation at the bottom. With the MS
      approach, protein secondary structure differences at different cooling rates
      could be detected for sucrose-lysozyme samples at the sucrose-lysozyme ratio of
      1.

PMID- 26305149
TI  - Controlled transport of captive bubbles on plastrons.
AB  - Captive bubbles that reside on superhydrophobic surfaces with plastrons move
      uncontrollably when tilted. A system based on creating moveable local apexes on
      flexible superhydrophobic foils is shown to allow controlled transport.
      Simulations done reveal that specific bubble transport speeds are needed to form
      concentration gradients suited for aerotaxis study and sensing. 

PMID- 26305150
TI  - Transferring Conditioned Partially Edentulous Ridge Form to a Master Cast.
AB  - Gingival conditioning techniques in prosthodontics aim to overcome bone and soft
      tissue defects that often compromise the outcome of restorations in terms of
      esthetics, function, and biocompatibility. Whatever the technique used, it is
      essential to reproduce a regular concave gingival outline in order to recreate
      the natural aspect of the relationship between teeth and gingiva, eliminating
      black triangles. Transferring the details of the conditioned soft tissue to the
      laboratory technician with precision may be challenging. The authors hereby
      propose a novel technique to transfer the clinical aspect of the conditioned soft
      tissue to the master cast, using a customized metal framework to help ensure
      accuracy.

PMID- 26305152
TI  - The effects of fear appeal message repetition on perceived threat, perceived
      efficacy, and behavioral intention in the extended parallel process model.
AB  - This study examined the effect of moderately repeated exposure (three times) to a
      fear appeal message on the Extended Parallel Processing Model (EPPM) variables of
      threat, efficacy, and behavioral intentions for the recommended behaviors in the
      message, as well as the proportions of systematic and message-related thoughts
      generated after each message exposure. The results showed that after repeated
      exposure to a fear appeal message about preventing melanoma, perceived threat in
      terms of susceptibility and perceived efficacy in terms of response efficacy
      significantly increased. The behavioral intentions of all recommended behaviors
      did not change after repeated exposure to the message. However, after the second
      exposure the proportions of both systematic and all message-related thoughts
      (relative to total thoughts) significantly decreased while the proportion of
      heuristic thoughts significantly increased, and this pattern held after the third
      exposure. The findings demonstrated that the predictions in the EPPM are likely
      to be operative after three exposures to a persuasive message. 

PMID- 26305151
TI  - Dye Encapsulation in Polynorbornene Micelles.
AB  - The encapsulation efficiency of high-Tg polynorbornene micelles was probed with a
      hydrophobic dye 2,6-diiodoboron-dipyrromethene (BODIPY). Changes in the visible
      absorption spectra of aggregated versus monomeric dye molecules provided a probe
      for assessing encapsulation. Polynorbornene micelles are found to be capable of
      loading up to one BODIPY dye per ten polymers. As the hydrophilic block size
      increased in the polymeric amphiphiles, more of the dye was incorporated within
      the micelles. This result is consistent with the dye associating with the polymer
      backbone in the shell of the micelles. The encapsulation rate varied
      significantly with temperature, and a slight dependence on micellar morphology
      was also noted. Additionally, we report a 740 MUs triplet lifetime for the
      encapsulated BODIPY dye. The lifetime is the longest ever recorded for a BODIPY
      triplet excited state at room temperature and is attributed to hindered triplet
      triplet annihilation in the high-viscosity micellar shell. 

PMID- 26305153
TI  - Localization-Delocalization in Bridged Mixed-Valence Metal Clusters: Vibronic PKS
      Model Revisited.
AB  - Here we describe a new vibronic model of mixed valence (MV) dimer inspired by the
      conventional Piepho, Krausz, and Schatz (PKS) approach. We attempted to partially
      lift the main restriction of the PKS model dealing with the vibronically
      independent moieties of a MV molecule. The refined version of the PKS model in
      which the bridging ligands are included deals with the three main interactions:
      electron transfer (integral t0) related to the high-symmetric ligand
      configuration, on-site vibronic coupling (parameter upsilon) arising from the
      modulation of the crystal field on the metal sites by the breathing displacements
      of their nearest ligand surroundings, and intercenter vibronic coupling
      (parameter zeta) describing the dependence of the electron transfer on ligand
      positions in the course of their breathing movement. We apply the modified model
      to the analysis of the adiabatic potentials and electronic density distributions
      in the minima of their lower sheets for the cases of one-electron MV dimer with
      long and short bridges and for the two-electron MV dimer exhibiting a valence
      disproportionation effect. The inclusion of the intercenter interaction in
      addition to the conventional PKS coupling is shown to produce a strong effect on
      the degree of localization in MV dimers and, in particular, on the assignments to
      the Robin and Day classes and on the conditions of stabilization of valence
      disproportionated states in bielectron transfer systems. 

PMID- 26305154
TI  - Flexible High-Energy Polymer-Electrolyte-Based Rechargeable Zinc-Air Batteries.
AB  - A thin-film, flexible, and rechargeable zinc-air battery having high energy
      density is reported particularly for emerging portable and wearable electronic
      applications. This freeform battery design is the first demonstrated by
      sandwiching a porous-gelled polymer electrolyte with a freestanding zinc film and
      a bifunctional catalytic electrode film. The flexibility of both the electrode
      films and polymer electrolyte membrane gives great freedom in tailoring the
      battery geometry and performance. 

PMID- 26305155
TI  - "Dying is dying, that's all": Structural violence and cultural projects in
      Malawian AIDS proverbs.
AB  - This paper examines three Malawian proverbs about AIDS: "AIDS came for people",
      "Dying is dying, that's all" and "It's in the flour". Proverbs permit Malawians
      to discuss the otherwise taboo topic of AIDS because they offer a special
      register and perform a footing shift, a rhetorical manoeuvre that allows the
      speaker to attribute problematic speech to someone else. The proverbs under
      consideration convey a sense of powerless in the face of the AIDS epidemic, which
      is an indicator of the effects of structural violence on the everyday lives of
      most Malawians. Despite the aura of timeless tradition generally conveyed by
      proverbs, the author argues that individual Malawians are actually using AIDS
      proverbs to align themselves with the pursuit of gendered cultural projects, such
      as multiple concurrent partner sex and transactional sex, which are not
      traditional at all. 

PMID- 26305156
TI  - Metabolic footprint of epiphytic bacteria on Arabidopsis thaliana leaves.
AB  - The phyllosphere, which is defined as the parts of terrestrial plants above the
      ground, is a large habitat for different microorganisms that show a high extent
      of adaption to their environment. A number of hypotheses were generated by
      culture-independent functional genomics studies to explain the competitiveness of
      specialized bacteria in the phyllosphere. In contrast, in situ data at the
      metabolome level as a function of bacterial colonization are lacking. Here, we
      aimed to obtain new insights into the metabolic interplay between host and
      epiphytes upon colonization of Arabidopsis thaliana leaves in a controlled
      laboratory setting using environmental metabolomics approaches. Quantitative
      nuclear magnetic resonance (NMR) and imaging high-resolution mass spectrometry
      (IMS) methods were used to identify Arabidopsis leaf surface compounds and their
      possible involvement in the epiphytic lifestyle by relative changes in compound
      pools. The dominant carbohydrates on the leaf surfaces were sucrose, fructose and
      glucose. These sugars were significantly and specifically altered after epiphytic
      leaf colonization by the organoheterotroph Sphingomonas melonis or the
      phytopathogen Pseudomonas syringae pv. tomato, but only to a minor extent by the
      methylotroph Methylobacterium extorquens. In addition to carbohydrates, IMS
      revealed surprising alterations in arginine metabolism and phytoalexin
      biosynthesis that were dependent on the presence of bacteria, which might reflect
      the consequences of bacterial activity and the recognition of not only pathogens
      but also commensals by the plant. These results highlight the power of
      environmental metabolomics to aid in elucidating the molecular basis underlying
      plant-epiphyte interactions in situ. 

PMID- 26305157
TI  - Rapid host switching in generalist Campylobacter strains erodes the signal for
      tracing human infections.
AB  - Campylobacter jejuni and Campylobacter coli are the biggest causes of bacterial
      gastroenteritis in the developed world, with human infections typically arising
      from zoonotic transmission associated with infected meat. Because Campylobacter
      is not thought to survive well outside the gut, host-associated populations are
      genetically isolated to varying degrees. Therefore, the likely origin of most
      strains can be determined by host-associated variation in the genome. This is
      instructive for characterizing the source of human infection. However, some
      common strains, notably isolates belonging to the ST-21, ST-45 and ST-828 clonal
      complexes, appear to have broad host ranges, hindering source attribution. Here
      whole-genome sequencing has the potential to reveal fine-scale genetic structure
      associated with host specificity. We found that rates of zoonotic transmission
      among animal host species in these clonal complexes were so high that the signal
      of host association is all but obliterated, estimating one zoonotic transmission
      event every 1.6, 1.8 and 12 years in the ST-21, ST-45 and ST828 complexes,
      respectively. We attributed 89% of clinical cases to a chicken source, 10% to
      cattle and 1% to pig. Our results reveal that common strains of C. jejuni and C.
      coli infectious to humans are adapted to a generalist lifestyle, permitting rapid
      transmission between different hosts. Furthermore, they show that the weak signal
      of host association within these complexes presents a challenge for pinpointing
      the source of clinical infections, underlining the view that whole-genome
      sequencing, powerful though it is, cannot substitute for intensive sampling of
      suspected transmission reservoirs. 

PMID- 26305160
TI  - Dr. Eula Bingham-Our colleague, mentor and friend-Neither retiring nor
      retreating.

PMID- 26305158
TI  - Molecular control of capillary morphogenesis and maturation by recognition and
      remodeling of the extracellular matrix: functional roles of endothelial cells and
      pericytes in health and disease.
AB  - This review addresses fundamental mechanisms underlying how capillaries form in
      three-dimensional extracellular matrices and how endothelial cells (ECs) and
      pericytes co-assemble to form capillary networks. In addition to playing a
      critical role in supplying oxygen and nutrients to tissues, recent work suggests
      that blood vessels supply important signals to facilitate tissue development.
      Here, we hypothesize that another major function of capillaries is to supply
      signals to suppress major disease mechanisms including inflammation, infection,
      thrombosis, hemorrhage, edema, ischemic injury, fibrosis, autoimmune disease and
      tumor growth/progression. Capillary dysfunction plays a key pathogenic role in
      many human diseases, and thus, this suppressing function may be attenuated and
      central toward the initiation and progression of disease. We describe how
      capillaries form through creation of EC-lined tube networks and vascular guidance
      tunnels in 3D extracellular matrices. Pericytes recruit to the abluminal EC tube
      surface within these tunnel spaces, and work together to assemble the vascular
      basement membrane matrix. These processes occur under serum-free conditions in 3D
      collagen or fibrin matrices and in response to five key growth factors which are
      stem cell factor, interleukin-3, stromal-derived factor-1alpha, fibroblast growth
      factor-2 and insulin. In addition, we identified a key role for EC-derived
      platelet-derived growth factor-BB and heparin-binding epidermal growth factor in
      pericyte recruitment and proliferation to promote EC-pericyte tube co-assembly
      and vascular basement membrane matrix deposition. A molecular understanding of
      capillary morphogenesis and maturation should lead to novel therapeutic
      strategies to repair capillary dysfunction in major human disease contexts
      including cancer and diabetes. 

PMID- 26305161
TI  - Site-Selective Trimetallic Heterogeneous Nanostructures for Enhanced
      Electrocatalytic Performance.
AB  - Trimetallic Au/Ag/Pt hetero-nanostructures (AAPHNs) with distinctive, designed
      morphology are synthesized by galvanic replacement reaction and a site-selective
      strategy. The three metals present on the surface are shown to act
      synergistically to enhance the electro-catalytic performance and durability for
      methanol oxidation. The described structural modification of the nanocomposites
      increases the range of potential applications to include both the oxygen
      reduction reaction in fuel cells and photocatalysis of the hydrogen evolution
      reaction. 

PMID- 26305162
TI  - Complete mitogenome sequences of a Korean spine loach, Iksookimia koreensis (Kim,
      1975).
AB  - Here, we present the complete mitogenome sequences from a Korean spine loach
      (Iksookimia koreensis Kim 1975), an endemic species of Korea. The total length of
      mitogenome was 16 563 bp, consisting of 13 protein-coding genes, 22 tRNA genes, 2
      rRNA genes and one control region (D-loop). Except for ND6 and eight tRNA genes,
      all of the other mitochondrial genes were encoded on the heavy strand. The
      control region harbored conserved sequence blocks (CSB-D, E, F, CSB-1, CBS-2 and
      CBS-3) and TA-nucleotide microsatellite repeats in its 3' end. Our complete
      mitogenomes will be valuable resources for phylogeny, genetics and conservation
      of the genus Iksookimia.

PMID- 26305163
TI  - Alkaline-Earth-Metal-Induced Liberation of Rare Allotropes of Elemental Silicon
      and Germanium from N-Heterocyclic Metallylenes.
AB  - The synthesis and striking reactivity of the unprecedented N-heterocyclic
      silylene and germylene ("metallylene") alkaline-earth metal (Ae) complexes of the
      type [(eta(5)-C5Me5)2Ae<-:E(N(t)BuCH)2] (3, 4, and 7-9; Ae = Ca, E = Ge 3; Ae =
      Sr, E = Ge 4; Ae = Sr, E = Si 7; Ae = Ba, E = Si 8; Ae = Ba, E = Ge 9) are
      reported. All complexes have been characterized by spectroscopic means, and their
      bonding situations investigated by density functional theory (DFT) methods.
      Single-crystal X-ray diffraction analyses of examples revealed relatively long Si
      Ae and Ge-Ae distances, respectively, indicative of weak E:->Ae (E = Si, Ge)
      dative bonds, further supported by the calculated Wiberg bond indices , which are
      rather low in all cases (~0.5). Unexpectedly, the complexes undergo facile
      transformation to 1,4-diazabuta-1,3-diene Ae metal complexes of the type [(eta(5)
      C5Me5)2Ae(kappa(2)-{N(t)Bu?CHCH?N(t)Bu})] (Ae = Sr 10, Ae = Ba 11) or in the case
      of calcium to the dinuclear complex [(eta(5)-C5Me5)2Ca<-:N((t)Bu)?CHCH?((t)Bu)N:
      >Ca(eta(5)-C5Me5)2] (12) under concomitant liberation of elemental silicon and
      germanium. The formation of elemental silicon and germanium is proven by
      inductively coupled plasma atomic emission spectroscopy, transmission electron
      microscopy, selected area electron diffraction, and energy dispersive X-ray
      spectroscopy. Notably, the decomposition of the Si(II)->Ba complex 8 produces
      allo-silicon, a rare allotropic form of elemental silicon. Similarly, the
      analogous Ge(II)->Ba complex 9, upon decomposition, forms tetragonal germanium, a
      dense and rare allotrope of elemental germanium. The energetics of this
      unprecedented alkaline-earth-metal-induced liberation of elemental silicon and
      germanium was additionally studied by DFT methods, revealing that the
      transformations are pronouncedly exergonic and considerably larger for the N
      heterocyclic germylene complexes than those of the corresponding silicon
      analogues. 

PMID- 26305164
TI  - Chemical Vapor Deposition of High-Quality and Atomically Layered ReS2.
AB  - Recently, anisotropic 2D materials, such as black phosphorus and rhenium
      disulfides (ReS2 ), have attracted a lot attention because of their unique
      applications on electronics and optoelectronics. In this work, the direct growth
      of high-quality ReS2 atomic layers and nanoribbons has been demonstrated by using
      chemical vapor deposition (CVD) method. A possible growth mechanism is proposed
      according to the controlled experiments. The CVD ReS2-based filed-effect
      transistors (FETs) show n-type semiconducting behavior with a current on/off
      ratio of ~10(6) and a charge carrier mobility of ~9.3 cm(2) Vs(-1). These results
      suggested that the quality of CVD grown ReS2 is comparable to mechanically
      exfoliated ReS2, which is also further supported by atomic force microscopy
      imaging, high-resolution transmission electron microscopy imaging and thickness
      dependent Raman spectra. The study here indicates that CVD grown ReS2 may pave
      the way for the large-scale fabrication of ReS2-based high-performance
      optoelectronic devices, such as anisotropic FETs and polarization detection.

PMID- 26305165
TI  - Hard X-ray Photoelectron Spectroscopy (HAXPES) Investigation of the Silicon Solid
      Electrolyte Interphase (SEI) in Lithium-Ion Batteries.
AB  - Binder-free silicon (BF-Si) nanoparticle anodes were cycled with 1.2 M LiPF6 in
      ethylene carbonate (EC), fluoroethylene carbonate (FEC), or EC with 15% FEC
      (EC:FEC), extracted from cells and analyzed by Hard X-ray Photoelectron
      Spectroscopy (HAXPES). All of the electrolytes generate an SEI which is
      integrated with Si containing species. The EC and EC:FEC electrolytes result in
      the generation of LixSiOy after the first cycle while LixSiOy is only observed
      after five cycles for the FEC electrolyte. The SEI initially generated from the
      EC electrolyte is primarily composed of lithium ethylene dicarbonate (LEDC) and
      LiF. However, after five cycles, the composition changes, especially near the
      surface of silicon because of decomposition of the LEDC. The SEI generated from
      the EC:FEC electrolytes contains LEDC, LiF, and poly(FEC) and small changes are
      observed upon additional cycling. The SEI generated with the FEC electrolyte
      contains LiF and poly(FEC) and small changes are observed upon additional
      cycling. The stability of the SEI correlates with the observed capacity retention
      of the cells. 

PMID- 26305166
TI  - Medical linear accelerator mounted mini-beam collimator: design, fabrication and
      dosimetric characterization.
AB  - The goal of this work was to design, build and experimentally characterize a
      linear accelerator mounted mini-beam collimator for use at a nominal 6 MV beam
      energy. Monte Carlo simulation was used in the design and dosimetric
      characterization of a compact mini-beam collimator assembly mounted to a medical
      linear accelerator. After fabrication, experimental mini-beam dose profiles and
      central axis relative output were measured and the results used to validate the
      simulation data. The simulation data was then used to establish traceability back
      to an established dosimetric code of practice. The Monte Carlo simulation work
      revealed that changes in collimator blade width have a greater influence on the
      valley-to-peak dose ratio than do changes in blade height. There was good
      agreement between the modeled and measured profile data, with the exception of
      small differences on either side of the central peak dose. These differences were
      found to be systematic across all depths and result from limitations associated
      with the collimator fabrication. Experimental mini-beam relative output and
      simulation data agreed to better than +/- 2.0%, which is well within the level of
      uncertainty required for dosimetric traceability of non-standard field
      geometries. A mini-beam collimator has now been designed, built and
      experimentally characterized for use with a commercial linear accelerator
      operated at a nominal 6 MV beam energy.

PMID- 26305167
TI  - Estimating a neutral reference for electroencephalographic recordings: the
      importance of using a high-density montage and a realistic head model.
AB  - OBJECTIVE: In electroencephalography (EEG) measurements, the signal of each
      recording electrode is contrasted with a reference electrode or a combination of
      electrodes. The estimation of a neutral reference is a long-standing issue in EEG
      data analysis, which has motivated the proposal of different re-referencing
      methods, among which linked-mastoid re-referencing (LMR), average re-referencing
      (AR) and reference electrode standardization technique (REST). In this study we
      quantitatively assessed the extent to which the use of a high-density montage and
      a realistic head model can impact on the optimal estimation of a neutral
      reference for EEG recordings. APPROACH: Using simulated recordings generated by
      projecting specific source activity over the sensors, we assessed to what extent
      AR, REST and LMR may distort the scalp topography. We examined the impact
      electrode coverage has on AR and REST, and how accurate the REST reconstruction
      is for realistic and less realistic (three-layer and single-layer spherical) head
      models, and with possible uncertainty in the electrode positions. We assessed
      LMR, AR and REST also in the presence of typical EEG artifacts that are mixed in
      the recordings. Finally, we applied them to real EEG data collected in a target
      detection experiment to corroborate our findings on simulated data. MAIN RESULTS:
      Both AR and REST have relatively low reconstruction errors compared to LMR, and
      that REST is less sensitive than AR and LMR to artifacts mixed in the EEG data.
      For both AR and REST, high electrode density yields low re-referencing
      reconstruction errors. A realistic head model is critical for REST, leading to a
      more accurate estimate of a neutral reference compared to spherical head models.
      With a low-density montage, REST shows a more reliable reconstruction than AR
      either with a realistic or a three-layer spherical head model. Conversely, with a
      high-density montage AR yields better results unless precise information on
      electrode positions is available. SIGNIFICANCE: Our study is the first to
      quantitatively assess the performance of EEG re-referencing techniques in
      relation to the use of a high-density montage and a realistic head model. We hope
      our study will help researchers in the choice of the most effective re
      referencing approach for their EEG studies.

PMID- 26305168
TI  - Cost-Effectiveness Analysis of the Diagnosis and Treatment of Primary
      Aldosteronism in Japan.
AB  - Approximately 10% of cases of hypertension in Japan are caused by primary
      aldosteronism (PA), amounting to about 4 million patients in total. Primary
      aldosteronism due to unilateral aldosterone hypersecretion is potentially curable
      by adrenalectomy. The clinical benefits of identifying and treating PA have been
      reported internationally, but its cost-effectiveness is unclear. We examined
      whether diagnosing and treating hidden PA in hypertensive population was cost
      effective compared with suboptimal treatment. Our hypothetical patient was a 50
      year-old man diagnosed with stage I-III hypertension. We established a Markov
      decision model based on plausible clinical pathways and prognoses of PA. We
      applied cost-effectiveness analysis comparing a comprehensive diagnostic strategy
      for PA (measurement of plasma aldosterone/renin ratio, 2 loading tests, imaging,
      and selective adrenal venous sampling) with a suboptimal strategy to manage
      hypertension by medication unless the typical signs of PA or other complication
      were manifest. Outcome measures were expected costs, expected effectiveness, and
      incremental cost-effectiveness ratio. The robustness of the findings was
      established by one-way and scenario sensitivity analyses. The comprehensive PA
      diagnostic strategy increased the expected costs by 64 004 JPY and expected life
      years by 0.013 compared with standard treatment. The incremental cost
      effectiveness ratio for the diagnosis of PA was 4 923 385 JPY per year. Our
      findings were sensitive to the outcomes of screening and treatment, and the costs
      of continuous or periodic medication for hypertension and the treatment of stroke
      and its complications. 

PMID- 26305169
TI  - In vitro characterization of chicken bone marrow-derived dendritic cells
      following infection with very virulent infectious bursal disease virus.
AB  - Infectious bursal disease is caused by infectious bursal disease virus (IBDV), an
      immunosuppressive virus that targets immune cells such as B cells and
      macrophages. However, the involvement of dendritic cells (DCs) during IBDV
      infection is not well understood. In this study the in vitro effects of live and
      inactivated very virulent IBDV (vvIBDV) UPM0081 on bone marrow-derived DCs (BM
      DC) were characterized and compared with BM-DC treated with lipopolysaccharide
      (LPS). Morphologically, BM-DC treated with LPS and vvIBDV showed stellate shape
      when compared to immature BM-DC. In addition, LPS-treated and both live and
      inactivated vvIBDV-infected BM-DC expressed high levels of double positive CD86
      and major histocompatibility complex class II antigens (>20%). vvIBDV-infected BM
      DC showed significantly higher numbers of apoptotic cells compared to LPS.
      Replication of vvIBDV was detected in the infected BM-DC as evidenced by the
      increased expression of VP3 and VP4 IBDV antigens based on flow cytometry, real
      time polymerase chain reaction and immunofluorescence tests. Levels of different
      immune-related genes such as interleukin-1beta (IL-1beta), CXCLi2 (IL-8), IL-18,
      interferon gamma (IFN-gamma, IL-12alpha, CCR7 and Toll-like receptor-3 (TLR3)
      were measured after LPS and vvIBDV treatments. However, marked differences were
      noticed in the onset and intensity of the gene expression between these two
      treatment groups. LPS was far more potent than live and inactivated vvIBDV in
      inducing the expression of IL-1beta, IL-18 and CCR7 while expression of Th1-like
      cytokines, IFN-gamma and IL-12alpha were significantly increased in the live
      vvIBDV treatment group. Meanwhile, the expression of TLR3 was increased in live
      vvIBDV-infected BM-DC as compared to control. Inactivated vvIBDV-treated BM-DC
      failed to stimulate IFN-gamma, IL-12alpha and TLR3 expressions. This study
      suggested that BM-DC may serve as another target cells during IBDV infection
      which require further confirmation via in vivo studies. 

PMID- 26305170
TI  - Platinum Nanoparticles: Efficient and Stable Catechol Oxidase Mimetics.
AB  - Although enzyme-like nanomaterials have been extensively investigated over the
      past decade, most research has focused on the peroxidase-like, catalase-like, or
      SOD-like activity of these nanomaterials. Identifying nanomaterials having
      oxidase-like activities has received less attention. In this study, we
      demonstrate that platinum nanoparticles (Pt NPs) exhibit catechol oxidase-like
      activity, oxidizing polyphenols into the corresponding o-quinones. Four unique
      approaches are employed to demonstrate the catechol oxidase-like activity exerted
      by Pt NPs. First, UV-vis spectroscopy is used to monitor the oxidation of
      polyphenols catalyzed by Pt NPs. Second, the oxidized products of polyphenols are
      identified by ultrahigh-performance liquid chromatography (UHPLC) separation
      followed by high-resolution mass spectrometry (HRMS) identification. Third,
      electron spin resonance (ESR) oximetry techniques are used to confirm the O2
      consumption during the oxidation reaction. Fourth, the intermediate products of
      semiquinone radicals formed during the oxidation of polyphenols are determined by
      ESR using spin stabilization. These results indicate Pt NPs possess catechol
      oxidase-like activity. Because polyphenols and related bioactive substances have
      been explored as potent antioxidants that could be useful for the prevention of
      cancer and cardiovascular diseases, and Pt NPs have been widely used in the
      chemical industry and medical science, it is essential to understand the
      potential effects of Pt NPs for altering or influencing the antioxidant activity
      of polyphenols. 

PMID- 26305171
TI  - Patient-Inspired Engineering and Nanotechnology.

PMID- 26305173
TI  - When two is not enough: a CtIP tetramer is required for DNA repair by Homologous
      Recombination.
AB  - Homologous recombination (HR) is central to the repair of double-strand DNA
      breaks that occur in S/G2 phases of the cell cycle. HR relies on the CtIP protein
      (Ctp1 in fission yeast, Sae2 in budding yeast) for resection of DNA ends, a key
      step in generating the 3'-DNA overhangs that are required for the HR strand
      exchange reaction. Although much has been learned about the biological importance
      of CtIP in DNA repair, our mechanistic insight into its molecular functions
      remains incomplete. It has been recently discovered that CtIP and Ctp1 share a
      conserved tetrameric architecture that is mediated by their N-terminal domains
      and is critical for their function in HR. The specific arrangement of protein
      chains in the CtIP/Ctp1 tetramer indicates that an ability to bridge DNA ends
      might be an important feature of CtIP/Ctp1 function, establishing an intriguing
      similarity with the known ability of the MRE11-RAD50-NBS1 complex to link DNA
      ends. Although the exact mechanism of action remains to be elucidated, the
      remarkable evolutionary conservation of CtIP/Ctp1 tetramerisation clearly points
      to its crucial role in HR. 

PMID- 26305174
TI  - Catalytic Asymmetric Four-Component Reaction for the Rapid Construction of 3,3
      Disubstituted 3-Indol-3'-yloxindoles.
AB  - A Rh(II)/chiral phosphoric acid cocatalyzed four-component reaction of indoles, 3
      diazooxindoles, arylamines, and ethyl glyoxylate is developed, offering an
      extremely efficient strategy for the construction of 3,3-disubstituted 3-indol-3'
      yloxindoles with excellent diastereoselectivities and high to excellent
      enantioselectivities. This transformation is proposed to proceed through a
      Mannich-type trapping of the zwitterionic intermediate generated from a metal
      carbene and an indole with an iminoester derived from an arylamine and a
      glyoxylate. 

PMID- 26305175
TI  - Relationship between different push-off variables and start performance in
      experienced swimmers.
AB  - The objective of this study was to determine the relationship between different
      variables measured with a force plate during the swimming start push-off phase
      and start performance presented by times to 5, 10 and 15 m. Twenty-one women from
      the Slovenian national swimming team performed two different swim starts
      (freestyle and undulatory) on a portable force plate to a distance further than
      15 m. Correlations between push-off variables and times to 5, 10 and 15 m were
      quantified through Pearson's product-moment correlation coefficient (r). The
      variables that significantly correlated (p < .05) to all times measured in the
      two starts performed were: average horizontal acceleration (freestyle: r = -0.58
      to -0.71; and undulatory: r = -0.55 to -0.66), horizontal take-off velocity
      (freestyle: r = -0.56 to -0.69; and undulatory: r = -0.53 to -0.67) and resultant
      take-off velocity (freestyle: r = -0.53 to -0.65; and undulatory: r = -0.52 to 
      0.61). None of the variables derived from the vertical force were correlated to
      swimming start performance (p > .05). Based on the results of this study, we can
      conclude that horizontal take-off velocity and average horizontal acceleration
      (calculated as the average horizontal force divided by swimmer's body mass) are
      the variables most related to swimming start performance in experienced swimmers,
      and therefore could be the preferred measures to monitor swimmers' efficiency
      during the push-off phase.

PMID- 26305176
TI  - Pro: Corticosteroids Are Useful in the Management of HAPE.

PMID- 26305177
TI  - Resveratrol offers protection to oxidative stress induced by ferrous ascorbate in
      bovine spermatozoa.
AB  - Resveratrol (RES) is a natural polyphenol and phytoestrogen exhibiting
      cardioprotective, anticancer, antibacterial and vasorelaxing properties. It is
      also a powerful reactive oxygen species (ROS) scavenger and chelating agent. This
      study was designed to determine the efficiency of RES to reverse the ROS-mediated
      impairment of the motility, viability and intracellular antioxidant profile of
      bovine spermatozoa. Spermatozoa were washed out of fresh bovine semen, suspended
      in 2.9% sodium citrate and subjected to RES treatment (5, 10, 25 and 50 MUmol L(
      1)) in the presence or absence of a pro-oxidant, i.e., ferrous ascorbate (FeAA;
      150 MUmol L(-1) FeSO4 and 750 MUmol L(-1) ascorbic acid) during a 6-h in vitro
      culture. Spermatozoa motion parameters were assessed using the SpermVision
      computer-aided sperm analysis (CASA) system. Cell viability was examined with the
      metabolic activity (MTT) assay, and the nitroblue-tetrazolium (NBT) test was
      applied to quantify the intracellular superoxide formation. Cell lysates were
      prepared at the end of the in vitro experiments in order to investigate the
      intracellular activity of superoxide dismutase (SOD), catalase (CAT), as well as
      the concentrations of glutathione (GSH) and malondialdehyde (MDA). FeAA treatment
      led to a reduced sperm motility (P < 0.001) and viability (P < 0.001), decreased
      the antioxidant parameters of the samples (P < 0.001 in case of SOD; P < 0.01
      with respect to CAT; P < 0.05 in relation to GSH) but increased the superoxide
      production (P < 0.001) and lipid peroxidation (P < 0.001). RES supplementation
      resulted in a preservation of the spermatozoa vitality and antioxidant
      characteristics (P < 0.001 in case of SOD; P < 0.01 with respect to 25-50 MUmol
      L(-1) RES and P < 0.05 in relation to 10 MUmol L(-1) RES; P < 0.05 in case of
      GSH), with 50 MUmol L(-1) RES proving to be the most effective RES concentration.
      Our results suggest that RES possesses significant antioxidant properties that
      may prevent the deleterious effects caused by ROS to spermatozoa, and preserve
      the fertilization potential of male reproductive cells.

PMID- 26305178
TI  - Editorial.

PMID- 26305179
TI  - A role of the FDG-PET/CT in the differential diagnosis between elderly onset
      rheumatoid arthritis and polymyalgia rheumatica; Comment on the study by Dr.
      Takahashi et al.

PMID- 26305180
TI  - Disclosure of a stigmatized identity: A qualitative study of the reasons why
      people choose to tell or not tell others about their traumatic brain injury.
AB  - OBJECTIVE: To investigate what goals influence the decisions of people with a
      traumatic brain injury to disclose (or not to disclose) information about their
      brain injury. METHOD: Ten people with a traumatic brain injury were interviewed
      about disclosing information about their injury to others. Thematic analysis was
      used to analyse the data. RESULTS: The report focuses on disclosure to people
      other than immediate family and close friends. Reasons for not disclosing
      included concern about negative reactions from others, feelings of shame about
      the injury, wanting to avoid getting distressed, wanting to fit in, lack of
      interest from others and the perception that the stress associated with the act
      of disclosing outweighed the benefits. Reasons for disclosing included obtaining
      emotional and practical support from others, the emotional release obtained from
      disclosure, the need to explain their behaviour to others and giving others the
      benefit of their experience. Experience of negative and stigmatizing reactions
      from others was common. Participants varied in their willingness to disclose.
      CONCLUSION: Disclosure can have important advantages and disadvantages. Some
      people with a TBI may need support in making optimal decisions about disclosure.

PMID- 26305181
TI  - Discovery of Potent 17beta-Hydroxywithanolides for Castration-Resistant Prostate
      Cancer by High-Throughput Screening of a Natural Products Library for Androgen
      Induced Gene Expression Inhibitors.
AB  - Prostate cancer (PC) is the second most prevalent cancer among men in Western
      societies, and those who develop metastatic castration-resistant PC (CRPC)
      invariably succumb to the disease. The need for effective treatments for CRPC is
      a pressing concern, especially due to limited durable responses with currently
      employed therapies. Here, we demonstrate the successful application of a high
      throughput gene-expression profiling assay directly targeting genes of the
      androgen receptor pathway to screen a natural products library leading to the
      identification of 17beta-hydroxywithanolides 1-5, of which physachenolide D (5)
      exhibited potent and selective in vitro activity against two PC cell lines, LNCaP
      and PC-3. Epoxidation of 5 afforded physachenolide C (6) with higher potency and
      stability. Structure-activity relationships for withanolides as potential anti-PC
      agents are presented together with in vivo efficacy studies on compound 6,
      suggesting that 17beta-hydroxywithanolides are promising candidates for further
      development as CRPC therapeutics. 

PMID- 26305182
TI  - (Not) getting political: indigenous women and preventing mother-to-child
      transmission of HIV in West Papua.
AB  - This paper builds on critiques that call for a more nuanced and contextualised
      understanding of conditions that affect HIV prevention by looking at West Papuan
      women's experiences of prevention of mother-to-child transmission services.
      Drawing on qualitative, ethnographic research with indigenous women and health
      workers, the paper demonstrates that women experience poor-quality HIV education
      and counselling, and that indigenous practices and concerns are largely not
      addressed by HIV services. We attribute this to a combination of national anti
      indigenous and anti-separatist political concerns with donor-led interventions
      that result in limited localisation and reduced effectiveness of HIV prevention
      measures. In West Papua, services are needed that enhance cooperation and shared
      commitment, and that acknowledge and work to overcome existing inequalities,
      ethnic tensions and discrimination in the health system. Beyond Indonesia, donor
      led HIV programmes and interventions need to balance avoidance of politically
      sensitive issues with complicity in perpetuating health inequalities. Translating
      global health interventions and donor priorities into locally compelling HIV
      prevention activities involves more than navigating local cultural and religious
      beliefs. Programme development and implementation strategies that entail
      confronting structural questions as well as social hierarchies, cleavages and
      silences are needed to render more effective services; strategies that are
      inherently political. 

PMID- 26305183
TI  - An Untraveled Road: The Integration of Palliative Care with Nephrology.

PMID- 26305186
TI  - Effects of a process-based cognitive training intervention for patients with
      stress-related exhaustion.
AB  - Stress-related exhaustion has been linked to a pattern of selective cognitive
      impairments, mainly affecting executive functioning, attention and episodic
      memory. Little is known about potential treatments of these cognitive deficits.
      The purpose of this study was to evaluate the effects of a process-based
      cognitive training intervention, designed to target the specific cognitive
      impairments associated with stress-related exhaustion. To this end, patients
      diagnosed with exhaustion disorder (ED) were randomized to either a multimodal
      stress rehabilitation program with the addition of a process-based cognitive
      training intervention (training group, n = 27) or a treatment-as-usual control
      condition, consisting of multimodal stress rehabilitation with no additional
      training (control group, n = 32). Treatment effects were evaluated through an
      extensive cognitive test battery, assessing both near and far transfer effects,
      as well as self-report forms regarding subjective cognitive complaints and
      burnout levels. Results showed pronounced training-related improvements on the
      criterion updating task (p < 0.001). Further, evidence was found of selective
      near transfer effects to updating (p = 0.01) and episodic memory (p = 0.04).
      Also, the trained group reported less subjective memory complaints (p = 0.02) and
      levels of burnout decreased for both groups, but more so for the trained group (p
      = 0.04), following the intervention. These findings suggest that process-based
      cognitive training may be a viable method to address the cognitive impairments
      associated with ED. 

PMID- 26305187
TI  - RTVP-1 regulates glioma cell migration and invasion via interaction with N-WASP
      and hnRNPK.
AB  - Glioblastoma (GBM) are characterized by increased invasion into the surrounding
      normal brain tissue. RTVP-1 is highly expressed in GBM and regulates the
      migration and invasion of glioma cells. To further study RTVP-1 effects we
      performed a pull-down assay using His-tagged RTVP-1 followed by mass spectrometry
      and found that RTVP-1 was associated with the actin polymerization regulator, N
      WASP. This association was further validated by co-immunoprecipitation and FRET
      analysis. We found that RTVP-1 increased cell spreading, migration and invasion
      and these effects were at least partly mediated by N-WASP. Another protein which
      was found by the pull-down assay to interact with RTVP-1 is hnRNPK. This protein
      has been recently reported to associate with and to inhibit the effect of N-WASP
      on cell spreading. hnRNPK decreased cell migration, spreading and invasion in
      glioma cells. Using co-immunoprecipitation we validated the interactions of
      hnRNPK with N-WASP and RTVP-1 in glioma cells. In addition, we found that
      overexpression of RTVP-1 decreased the association of N-WASP and hnRNPK. In
      summary, we report that RTVP-1 regulates glioma cell spreading, migration and
      invasion and that these effects are mediated via interaction with N-WASP and by
      interfering with the inhibitory effect of hnRNPK on the function of this protein.

PMID- 26305188
TI  - Molecular characterization of a selected cohort of patients affected by pulmonary
      metastases of malignant melanoma: Hints from BRAF, NRAS and EGFR evaluation.
AB  - BACKGROUND: Melanoma is highly curable in early stages but holds devastating
      consequences in advanced phases with a median survival of 6-10 months. Lungs are
      a common metastasis target, but despite this, limited data are available on the
      molecular status of pulmonary lesions. MATERIALS AND METHODS: 25 patients with
      surgically resected melanoma lung metastases were screened for BRAF, NRAS, CKIT
      and EGFR alterations. The results were correlated with time to lung metastasis
      (TLM), relapse-free survival after metastasectomy (RFS) and overall survival
      (OS). RESULTS: BRAF or NRAS were mutated in 52% and 20% of cases while CKIT was
      unaffected. Chromosome 7 polysomy was detected in 47% of cases with 17.5% showing
      EGFR amplification and concomitant BRAF mutation. NRAS mutated patients developed
      LM within 5 yrs from primary melanoma with larger lesions compared with BRAF
      (mean diameter 3.3 +/- 2.2cm vs 1.9 +/- 1.1cm, p = 0.2). NRAS was also associated
      with a shorter median RFS and OS after metastasectomy. Moreover, Cox regression
      analysis revealed that NRAS mutation was the only predictive factor of shorter
      survival from primary melanoma (p = 0.039, OR = 5.5 (1.1-27.6)). CONCLUSIONS:
      Molecular characterization identifies advanced melanoma subgroups with distinct
      prognosis and therapeutic options. The presence of NRAS mutation was associated
      to a worse disease evolution.

PMID- 26305190
TI  - Trait-agreeableness influences individual reactions to a physician's affiliative
      behavior in a simulated bad news delivery.
AB  - We tested whether the personality trait of agreeableness predicts different
      individual reactions to the level of nonverbal affiliativeness shown by a
      physician, in the context of a simulated bad news delivery. We predicted that
      individuals with high levels of agreeableness would react better to a physician
      adopting a highly affiliative communication style compared to individuals with
      low levels of agreeableness. We used an experimental design with analogue
      patients. Eighty participants (40 men/40 women) were randomly assigned to watch a
      video of a physician who communicated a bad diagnosis either in a highly
      affiliative or in a less affiliative way. Participants reported their reactions
      of anger and trust in the physician, and completed the agreeableness scale of the
      NEO Five-Factor Inventory (NEO-FFI). In accordance with our predictions, the
      higher the agreeableness score of the participants, the less anger and the more
      trust they reported after viewing the high as compared to the low affiliative
      physician. These results suggest that people with high levels of agreeableness
      may be especially sensitive to highly affiliative physician nonverbal behavior
      when receiving bad news. 

PMID- 26305191
TI  - Response to Comment on "Enhanced Long-Term Nitrogen Removal and Its Quantitative
      Molecular Mechanism in Tidal Flow Constructed Wetlands".

PMID- 26305192
TI  - Rate Constant for the OH + CO Reaction at Low Temperatures.
AB  - Rate constants for the reaction of OH + CO -> products (1) have been measured
      using laser photolysis/laser-induced fluorescence (LP/LIF) over the temperature
      range 193-296 K and at pressures of 50-700 Torr of Ar and N2. The reaction was
      studied under pseudo-first-order conditions, monitoring the decay of OH in the
      presence of a large excess of CO. The rate constants can be expressed as a
      combination of bimolecular and termolecular components. The bimolecular component
      was found to be temperature-independent with an expression given by kbi(T) =
      (1.54 +/- 0.14) * 10(-13)[e(-(13+/-17)/T)] cm(3) molecule(-1) s(-1), with an
      error of one standard deviation. The termolecular component was fitted to the
      expression, kter = k0(T)[M]/[1 + (k0(T)[M]/kinfinity(T)] *
      0.6({1+[log10(k0(T)[M]/kinfinity(T))]2}-1) where k0(T) = k0(300)(T/300)(-n) and
      kinfinity(T) = kinfinity(300)(T/300)(-m). The parameters for k0(T) were
      determined to be k0(300) = (6.0+/-0.5) * 10(-33) cm(6) molecule(-2) s(-1) in N2
      and k0(300) = (3.4 +/- 0.3) * 10(-33) cm(6) molecule(-2) s(-1) in Ar, with n =
      1.9+/-0.5 and 2.0+/-0.4 in N2 and Ar, respectively. These parameters were
      determined using k0(T) and m from the NASA kinetics data evaluation (JPL
      Publication No. 10-6) since the experimental pressure range was far from the high
      pressure limit. Addition of low concentrations of O2 had no discernible effect on
      the mechanism of the OH + CO reaction but resulted in secondary reactions which
      regenerated OH.

PMID- 26305193
TI  - Feasibility and Diagnostic Accuracy of Supersonic Shear-Wave Elastography for the
      Assessment of Liver Stiffness and Liver Fibrosis in Children: A Pilot Study of 96
      Patients.
AB  - PURPOSE: To evaluate the feasibility of using supersonic shear-wave elastography
      (SSWE) in children and normal values of liver stiffness with the use of control
      patients of different ages (from neonates to teenagers) and the diagnostic
      accuracy of supersonic shear wave elastography for assessing liver fibrosis by
      using the histologic scoring system as the reference method in patients with
      liver disease, with a special concern for early stages of fibrosis. MATERIALS AND
      METHODS: The institutional review board approved this prospective study. Informed
      consent was obtained from parents and children older than 7 years. First, 51
      healthy children (from neonate to 15 years) were analyzed as the control group,
      and univariate and multivariate comparisons were performed to study the effect of
      age, transducer, breathing condition, probe, and position on elasticity values.
      Next, 45 children (from 1 month to 17.2 years old) who underwent liver biopsy
      were analyzed. SSWE measurements were obtained in the same region of the liver as
      the biopsy specimens. Biopsy specimens were reviewed in a blinded manner by a
      pathologist with the use of METAVIR criteria. The areas under the receiver
      operating characteristics curve (AUCs) were calculated for patients with fibrosis
      stage F0 versus those with stage F1-F2, F2 or higher, F3 or higher, and F4 or
      higher. RESULTS: A successful rate of SSWE measurement was 100% in 96 patients,
      including neonates. Liver stiffness values were significantly higher when an SC6
      1 probe (Aixplorer; SuperSonic Imagine SA, Aix-enProvence, France) was used than
      when an SL15-4 probe (Aixplorer) was used (mean +/- standard deviation, 6.94 kPa
      +/- 1.42 vs 5.96 kPa +/- 1.31; P = .006). There was no influence of sex, the
      location of measurement, or respiratory status on liver elasticity values (P =
      .41-.93), although the power to detect such a difference was low. According to
      the degree of liver fibrosis at liver biopsy, 88.5%-96.8% of patients were
      correctly classified, with AUCs of 0.90-0.98 (95% confidence interval [CI]: 0.8,
      1.0). The AUC for patients with stage F0 versus stage F1-F2 was 0.93 (95% CI:
      0.87, 0.99). CONCLUSION: SSWE allows accurate assessment of liver fibrosis, even
      in children with early stage (F1-F2) disease, and the choice of transducer
      influences liver stiffness values.

PMID- 26305189
TI  - Antimicrobial photodynamic inactivation in nanomedicine: small light strides
      against bad bugs.
AB  - The relentless advance of drug-resistance among pathogenic microbes, mandates a
      search for alternative approaches that will not cause resistance. Photodynamic
      inactivation (PDI) involves the combination of nontoxic dyes with harmless
      visible light to produce reactive oxygen species that can selectively kill
      microbial cells. PDI can be broad-spectrum in nature and can also destroy
      microbial cells in biofilms. Many different kinds of nanoparticles have been
      studied to potentiate antimicrobial PDI by improving photosensitizer solubility,
      photochemistry, photophysics and targeting. This review will cover photocatalytic
      disinfection with titania nanoparticles, carbon nanomaterials (fullerenes, carbon
      nanotubes and graphene), liposomes and polymeric nanoparticles. Natural polymers
      (chitosan and cellulose), gold and silver plasmonic nanoparticles, mesoporous
      silica, magnetic and upconverting nanoparticles have all been used for PDI. 

PMID- 26305194
TI  - Review of Risk Factors for Anastomotic Leakage in Colorectal Surgery.
AB  - Anastomotic leakage after colorectal surgery is a serious complication leading to
      increased morbidity and mortality. Multiple studies have found as risk factors
      for anastomotic leakage: male gender, obesity, preoperative steroid and non
      steroidal anti-inflammatory drug use, longer duration of operation, surgical
      experience and preoperative blood transfusion. The laparoscopic approach is not
      inferior to open surgery in terms of rate of anastomotic fistula. Several studies
      have also shown the ASA score and tumor distance from the anal verge as
      predictors for increased operative time and morbidity after laparoscopic total
      mesorectal excision. There is strong evidence that preoperative radiochemotherapy
      for rectal cancer increases the risk for anastomotic leakage. The preoperative
      bowel preparation does not reduce the incidence of postoperative leaks. The use
      of diversion stoma has not been shown to reduce leak rate, but mitigates the
      clinical effects of fistula. 

PMID- 26305195
TI  - Monitoring the Laryngeal Nerves During Thyroidectomy. Initial 115 Cases
      Experience.
AB  - The lesions of the laryngeal nerves, despite low incidence, are the most severe
      long term complications after thyroidectomy. Visualization after careful
      dissection of the recurrent laryngeal nerve (RLN) is now the golden standard
      among thyroid surgeons. We assessed traditional landmarks for the identification
      of RLN and anatomic high risk situation. The study also presented our initial
      experience using neuro monitoring of RLN (IONM) during surgery. The results show
      a recognizable Zuckerkandl tubercle in 162 of the 222 cases (72,97%). After
      dissection RLN was found posterior from TZ in 154 cases (95,06%) and lateral from
      TZ in 8 cases (4,93%). The identification of the Zuckerkandl tubercle is a useful
      landmark for RLN localization. As concerning high risk situations we found 2 non
      recurrent laryngeal nerves (both on the right side). Extra laryngeal ramification
      of RLN is an anatomical reality with significant incidence (23,8% in our study)
      and major surgical involvement. Extra laryngeal ramification of RLN occurs more
      often between the cross point with inferior thyroid artery and larynx entry
      point. Monitoring the branches of RLN we obtain major EMG signal on the anterior
      one. The surgical meaning is that the anterior branch carries the most important
      motor fibers and we have to pay extra care in the correct identification and
      preservation of it. From a total of 222 visually identified RLN we have 215
      nerves (96,84%) with positive EMG signal on monitoring. For 7 nerves (3,15%) we
      had no EMG signal. In 3 cases (2 total thyroidectomies and 1 lobectomy) involving
      5 RLN there was a false negative result caused by electrode malposition or
      desoldering from endotracheal tube. Our initial experience shows that IONM is
      harmless, easy to handle and a useful tool for identifying the nerve and confirm
      its integrity. More extended studies are needed to show if intraoperative
      monitoring decreases the rate of RLN iatrogenic injury.

PMID- 26305196
TI  - Cardiothyreosis: Pathogenic Conjectures, Clinical Aspects and Surgical Approach.
AB  - INTRODUCTION: The presence of striking cardiovascular manifestations were noted
      in the first descriptions of hyperthyroidism owing to Parry (1825) and Basedow
      (1840) in his famous Merseburg triad. Hyperthyroidism may either cause cardiac
      complications in individuals with a normal myocardium (genuine form of disorder)
      or complicate preexisting cardiac troubles. MATERIAL AND METHOD: An homogenous
      series of 49 cardiothyreosis, 11 males and 38 females, aged 12 - 78 (mean 45)
      years selected between 138 thyrotoxic patients operated on in a period of two
      decades is herein presented. There were registered 15 Basedow diseases, 16 toxic
      adenomas and 18 multinodular toxic goiters. Among these were found isolated or
      dominating when combined together, 21 cases with rhythm troubles (4 with
      extrasistolic arrhythmia and one with fibrilloflutter, 10 cases with cardiac
      failure and 9 cases with coronary cardiac disease. To these 7 hypertensive
      patients and two with mitral valvulopathy were added. In hyperthyroidism clinical
      diagnosis was confirmed on imaging exams and hormonal determinations while
      cardiovascular disturbances was ascertained by interrogatory, clinical signs, EKG
      and echocardiography. All our cases were operated on performing 33 total or near
      total thyroidectomies and 16 lobectomies without morbidity recording however 5
      postoperative tachyarrhythmias but finally most of them with good clinical
      results (87,7% cured or significantly ameliorated). DISCUSSIONS AND CONCLUSIONS:
      Pathogenic diagnosis of such so-called "cor thyreotoxicosis" is not always easy
      on account of cardiovascular syndrome which frequently overshowed the thyroid
      subclinical pictures or emergencies of new described entities as amidarone
      induced thyrotoxicosis. The single administration of a whole calculated dose of I
      131 with subsequent treatment with thyrostatics and B-blockers till remission of
      toxicosis is achieved can be chosen opposing to thyroidectomy after short
      medicamentous preparation which is effective in large thyromegalies and toxic
      adenomas.

PMID- 26305197
TI  - Pancreaticojejunostomy - Risk Anastomosis after Cephalic Pancreaticoduodenectomy.
AB  - INTRODUCTION: The authors bring to attention pancreaticojejunalanastomosis (PJA)
      performed after cephalic pancreaticoduodenectomy(CPD). This type of anastomosis
      is renowned forits high risk of complications. Among these complications,
      pancreatic fistula (PF) is distinguishable due to a significant frequency,
      averaging 10%. It is perhaps the most unsafe type of anastomosis in digestive
      surgery, due to its pancreatic partnership. Performing a sealed APJ can be
      considered a great achievement: a digestive lumen is set in contact with a
      brittleparenchymal structure, centred by a delicate excretory channel, difficult
      to anastomose in itself. MATERIAL AND METHODS: We studied two distinct groups of
      patients undergoing CPD. A first group - 58 cases operated on between 1967 and
      1983, and the second one - 70 cases operated on between 1984 - 2013. In all cases
      we performed PJA; by in-continuity loop technique in the first group, and with
      separate loop in the second group. In the second group we used a variant own
      technique that does not allow anastomotic loss of pancreatic fluid. Thus, a
      decline in the incidence of PF from 20% to 8% was obtained, the final percentage
      corresponding to group two. Of the 8% of patients with PF losses were recorded
      strictly at pancreatic level, with no bile or food contamination. Stenting was
      recorded for biliary- and pancreaticojejunal anastomoses in group two.
      DISCUSSIONS: The percentage of PF after CPD did not show anynotable revival when
      comparing the 1980s period to the present. Also, mortality due to FP is
      approaching 40%, adaunting figure. The multitude of technical options for
      restoring bowel movement after CPD, over 80 procedures, further confirms the lack
      of safety and trust in relation to PJA.The authors bring forward several surgical
      gestures addressing PJA, gestures capable of providing an 8% frequency of
      PF,percentage which we consider to be reasonable. CONCLUSIONS: The authors
      consider PJA stenting mandatory.Placing an isolated PJA on the short branch of
      the "Y", separate from the biliary and food flow, prevents the formation of a
      complex fistula. The proposed technique does not require a"duct - to - mucosa"
      type or "telescoping" type pancreaticojejunalanastomosis.

PMID- 26305198
TI  - Gastrointestinal Injuries in Blunt Abdominal Traumas.
AB  - AIM: To discuss the efficiency of RTS (Revised TraumaScore), ISS (Injury Severity
      Score), and factors that affect mortality and morbidity in gastrointestinal
      injuries due to blunt trauma.Method and methods: Patients with gastrointestinal
      injuries due to blunt trauma operated within the last six years have been studied
      retrospectively in terms of demographics,injury mechanism and localization,
      additional injuries, RTS and ISS, operative technique, morbidity, mortality and
      duration of hospitalization. FINDINGS: Of the eighteen cases, cause of injury was
      a traffic accident for 11 (61.1%), fall from height for 5 (27%) and physical
      attack for 2 (11%). Among the eighteen patients,there were 21 gastrointestinal
      injuries (11 intestinal, 6 colon,3 duodenum, 1 stomach). 10 (55.6%) had
      additional intraabdominal injuries while the number for extra-abdominal injuries
      were 12 (66.7%). Primary suture (10), segmentary resection (9) and pyloric
      exclusion (2) were the operations performed for the twenty-one gastrointestinal
      injuries.Although statistically not significant, 13(72.2%) patients with
      additional injuries compared with 5 (27.8%) patients with isolated
      gastrointestinal injuries, were found to have lower RTS (7.087/7.841), higher ISS
      (19.4/12.2), longer duration of hospitalization (11.5/8.4 day) as well as higher
      morbidity (7/1) and mortality (2/0) rates. Comparing the RTS (7.059/7.490) of
      patients who have and have not developed morbidity revealed no significant
      difference.However, ISS (23.9/12.2) was significantly higher in patients who have
      developed morbidity (p=0.003). RTS (6.085 7.445) and ISS (39.5/14.6) of patients
      who have survived were significantly different than patients who have not(p=0.037
      and p=0.023, respectively) CONCLUSION: Additional injuries in patients with
      gastrointestinal injury due blunt abdominal traumas increases, although not
      significantly, morbidity, mortality and duration of hospitalization even when
      operated early. High ISS is significantly related to the risk of both morbidity
      and mortality while low RTS is significantly related only to the mortality risk.

PMID- 26305199
TI  - Clinical and Paraclinical Criteria of Patient Selection for the Non-operative
      Treatment in Completely Responsive Rectal Cancer (after Neoadjuvant
      Radiochemotherapy).
AB  - INTRODUCTION: Neoadjuvant radiotherapy is included in the treatment protocols for
      rectal tumors in stages = T3. The use of neoadjuvant radiotherapy allowed the
      limit of surgical oncologic safety margin to decrease with 1-2 cm and the
      abdominoperineal resection to be able to be performed in tumors situated at 4 cm
      from the anal verge. This modification of the treatment strategy increased the
      use of low, ultra low and colo-anal anastomoses. GOAL: Through the analysis of
      these types of anastomoses and of the disadvantages of the abdomino-perineal
      resection, we aimed at performing a study on the patients which responded
      completely to radiotherapy by taking into account the criteria of oncologic
      safety and the sparing of the patients from surgical complications. MATERIAL AND
      METHOD: We performed a retrospective study on 171 patients with rectal cancer
      treated in the 1st Clinic of Surgery from the Bucharest Oncology Institute
      between October 2007 and December 2013. RESULTS: 141 patients received
      radiotherapy, out of which 9 responded completely. 5 of those 9 were not operated
      on and after variable clinical and paraclinical follow up (2-6 years),they did
      not present with local recurrence. CONCLUSIONS: Not performing surgery in the
      patients with rectal cancer with a complete response to radiotherapy is a good
      solution and must be taken after a correct information of the patient about
      rectal surgery with the condition of strictly observing the selection criteria of
      the patients.

PMID- 26305200
TI  - A Meta-Analysis of Quality of Life, Estimated by Questionnaires of the European
      Organization for Research and Treatment of Cancer (EORTC) after Rectal Cancer
      Surgery.
AB  - BACKGROUND: Rectal carcinoma is one of the most common cancers on a global scale.
      Although there were major improvements in its treatment during the last two
      decades, surgery is still the only curative method. However, is often complicated
      and can cause disorder of different aspects of the patients self-perception of
      health. The aim of this study is performing ofa meta-analysis for evaluation and
      comparison of the quality of liferesults after rectal cancer treatment. METHODS:
      Search of relevant articles, which were published between 2000 and 2015, was
      performed. The outcomes of abdominoperineal resection and anterior resection were
      analyzed with the EORTC's quality of life measuring instruments - quality-of-life
      questionnaire C30 (QLQ-C30)and quality-of-life questionnaire CR38 (QLQ-CR38). The
      assessment score, appropriate for the survey, was established at least one year
      after radical surgery. The Statistical Package for Social Sciences (SPSS) package
      of IBM Statistics, version 19 was used for the statistical analyses. RESULTS: 13
      studies, published between 2001 and 2015, have been presented in this meta
      analysis. Data from 1805 patients,with a mean age of 64.7 years, have been
      included. When comparing Miles extirpation and sphincter-sparing
      operations,statistical significance was detected for the following
      variables:social functioning (74.6 +/- 8.5 vs. 83.4 +/- 8.6, P =
      0.045),constipation (11 +/- 8.4 vs. 22.6 +/- 8.3, P = 0.032), and body image
      (67.9 +/- 14 vs. 82.5 +/- 9.1, P= 0.01). CONCLUSION: Preservation of the
      sphincter is a better treatment option that should be carefully considered.
      Dependently registered differences, our conviction for the rectal cancer care
      concern needs individualization of the approach in this surgery.It is essential
      that the policy of avoidance of abdominoperineal resection (APR) cannot currently
      be justified on the grounds of quality-of-life (QoL) results alone.

PMID- 26305201
TI  - Epidemiologic and Bacteriologic Study of the Burned Patients from the Plastic
      Surgery Department of the County Emergency Hospital of Ploiesti, over a 4 Years
      Period (2010-2013).
AB  - This study analyses the epidemiologic data and the bacteriologic results of a
      total number of 759 burned patients, which were treated and discharged from the
      Plastic Surgery Department of the County Emergency Hospital of Ploiesti, between
      01 01 2010 and 31 12 2013. The investigated parameter shave been: age and gender
      distribution, rural or urban population, burn etiology, total burn surface area
      (TBSA),TBSA, location and depth of lesions, therapeutic management,length of
      hospital stay, types of bacteria isolated from the infected wounds and their
      sensitivity to antibiotics, patients' mortality. The statistical analysis
      revealed the following results: mean age 51.33 +/- 18.44 years, male/female ratio
      1.35/1, rural/urban ratio 1.34/1, most common etiologies were scalds (44.8%) and
      flames (37.6%), mean TBSA 7.7 +/- 8.4%, main locations were the extremities,
      splitthickness skin grafting in 15% of the patients, hospital stay 15.57 +/-
      13.84 days, main bacteria isolated were Pseudomonas aeruginosa (26.3%) and
      Staphylococcus aureus (22.9%), mortality rate 0.13%. The best methods to decrease
      the burn morbidity are the burn and infection prevention, for which several
      measures are discussed.

PMID- 26305202
TI  - Cost Effectiveness Analysis of Knee Osteoarthritis Treatment.
AB  - INTRODUCTION: Resource allocation is challenging in times of economic restraint
      and cannot be based only on clinical judgments, but must also take into account
      economic aspects. A method for assessing patient outcome is to estimate the
      quality-adjusted life years (QALYs). These will quantify the benefit gained by a
      certain treatment by measuring the change in health-related quality of life with
      time. This study will assess the cost effectiveness of conservative management,
      consisting in rehabilitation program, and compare the cost effectiveness of total
      knee arthroplasty when implanted to a non operated arthritic knee with cost
      effectiveness of the same procedure following high tibial osteotomy. MATERIALS
      AND METHODS: This study reviewed 30 patients who were treated for knee
      osteoarthritis with rehabilitation care (group 1-G1), 30 patients who underwent
      unilateral TKA to an non-operated knee (group 2-G2) and 30 patients who underwent
      TKA following HTO for degenerative arthritis of the knee (group 3-G3). The
      economical endpoint were the total direct costs (Euro), based on DRG rates for
      procedures. The cost effectiveness analysis was assessed by the ratio between
      direct costs as assessed by the economical endpoint and the associated patient
      benefit as assessed by the clinical endpoint (EUR/QALY). RESULTS: No
      statistically significant differences was found between G2 and G3 regarding
      clinical or radiological outcomes of this study. Yet the patients who did not
      previously suffered a HTO procedure showed lower mean values of KSS, ROM and
      femurotibial angle. A significant benefit is observed for G2 and G3 towards G1
      patients. Neither a clinically relevant nor a statistically significant
      association between groups is observed in G2 and G3 (median benefit estimates 2.5
      versus 2.6 QALYs). Median benefit estimate for patients who did not previously
      suffered a HTO procedure was though smaller then benefit for those who did. A
      median cost effectiveness ratio of 1800 EUR/QALY (450 - 2000 EUR / QALY) was
      found based on the EuroQuol scores for G1; 1268 EUR/QALY (720 - 2160 EUR/QALY),
      for G2, and 1975 EUR/QALY (720 - 2160 EUR/QALY) for G3. DISCUSSION: Regarding
      surgical treatment, the results showed a statistically significant better cost
      benefit relation for patients from G2 (p 0,001). Conservative management for knee
      OA is neither clinically effective for pain or disease progression nor cost
      effective, when applied for late stages of OA. CONCLUSION: We report the lowest
      cost per QALY in the literature for TKA. If financial constraints is a cause for
      rationalizing the medical services, careful patient selection to optimise the
      clinical and economical aspects of procedures may help to improve further the
      cost-effectiveness of these interventions.

PMID- 26305203
TI  - Successful Robotic Cystogastrostomy after Failed Endoscopic Drainage for Infected
      Pancreatic Fluid Collection Post Distal Pancreatectomy.
AB  - We are presenting the management of an infected pancreatic fluid collection that
      occurred six months after distal pancreatectomy in the setting of a radical
      resection for adrenal carcinoma. Progressive increase in size of the cyst and
      failure of endoscopic drainage represented the surgical indications for
      cystogastrostomy. The procedure was facilitated by robotic approach with da Vinci
      Surgical System. Though as per current literature the endoscopic drainage has
      largely been accepted for this pathology due to its high rate of success and a
      low rate of complications, in this particular case, surgical drainage by the
      minimally invasive robotic approach was successful after endoscopic approach has
      failed. 

PMID- 26305204
TI  - Metachronous Ampulla of Vater Carcinoma after Curative-Intent Surgery for
      Klatskin Tumor.
AB  - Resection represents the single hope for long-term survival in a patient
      diagnosed with a hilar cholangiocarcinoma (Klatskin tumor). However, the largest
      part of these patients develops a recurrent disease. Second metachronous
      periampullary cancers after a curative-intent surgery for a Klatskin tumor
      represent an exceptional pathology, and the management of these patients was
      poorly documented. Hereby, it is presented a 32-year-old patient with bile duct
      resection, left hemi-hepatectomy and loco-regional lymph nodes dissection, for a
      type IIIB Bismuth-Corlette Klatskin tumor, which, furthermore, 6 years later,
      underwent a pancreaticoduodenectomy for a metachronous carcinoma of the ampulla
      of Vater. The management and outcomes were discussed in the reported case, along
      with a literature review of the previously published patients. In conclusion, a
      metachronous periampullary carcinoma after resection of a Klatskin tumor should
      be distinguished from a loco-regional recurrent disease. While most of the
      patients with recurrences are suitable to only chemotherapy and or radiotherapy,
      a second curative-intent surgery (i.e., pancreaticoduodenectomy) is feasible in
      the largest part of the patients with a metachronous cancer, with good long-term
      outcomes. 

PMID- 26305205
TI  - Extraskeletal Osteosarcoma of the Omentum with Aggressive Development.
AB  - For the first time extraskeletal osteosarcomas (ESOS) were described by Wilson in
      1941. They are extremely rare neoplasms, presenting 4% of all osteosarcomas and
      1,2% of all soft-tissue sarcomas. About 300 cases have been reported in the
      literature up to date. We present a 66-year-old female patient, admitted in the
      clinic because of acute bleeding in retroperitoneal space. Revision of the
      retroperitoneal space and haemostasis were performed. The patient was re-operated
      because postoperative bowel obstruction. The reason for it was intestinal
      infiltration from large tumor of the omentum, determined histopathologically as
      ESOS. The case was considered as an unresectable neoplasm so a colostomy was
      performed. In the literature we found 3 case reports of ESOS, originated from
      omentum. 

PMID- 26305206
TI  - Hematochezia due to Caecal Angiodysplazia led to Diagnosis of a Transverse Colon
      Cancer in a Young Female Patient: Case Report and Literature Review.
AB  - We present an unusual case of a caecal angiodysplasia whose bleeding determined
      the discovery of a mid-transverse colon cancer in a 26 years old female patient.
      After the initial successful angiographic treatment of the caecal lesion the
      patient underwent laparoscopic - assisted transverse colectomy. The postoperative
      evolution was favorable, without resumption of bleeding episodes and rapid social
      reintegration. The histopathology revealed mucinous adenocarcinoma that
      penetrates the visceral serous with 7 lymph nodes invasion of 18 examined. As a
      result of the advanced stage, pT4aN2bM0 - stage IIIC, the life expectancy at 5
      years is between 30 to 50%. 

PMID- 26305207
TI  - Intestinal Intussusception by Monophasic Synovial Sarcoma: Case Report and
      Literature Review.
AB  - INTRODUCTION: Synovial sarcomas are rare malignant tumors of soft tissues,
      arising mainly from periarticular structures. Gastrointestinal localizations are
      unusual presentation of these rare sarcomas. METHODS: We present the case of a 56
      years old man with monophasic synovial sarcoma, arising primarily from the
      ileum, and causing intussusception. A review of the literature was conducted to
      gather information about this rare sarcoma. RESULTS: We found that the criteria
      normally used to determine the prognosis in patients with monophasic synovial
      sarcoma of soft tissue are poorly applicable for gastrointestinal localizations.
      CONCLUSIONS: A better characterization of these tumors could identify them as a
      distinct entity, compared with monophasic synovial sarcomas of soft tissues.

PMID- 26305208
TI  - Total Pelvic Exenteration for Recurrent Endometrial Sarcoma - A Case Report.
AB  - Endometrial stromal sarcomas are rare gynecologic malignancies characterized by
      the presence of cells that resemble those of the endometrial stroma during the
      prolipferative phase of the menstrual cycle. They are classified as low grade or
      high grade tumors depending on the mitotic index, the second one being usually
      associated with poor prognosis and high recurrence rate. We present the case of a
      46-year-old patient who was previously submitted to surgery for an endometrial
      stromal sarcoma followed by adjuvant radiotherapy; 18 months later she was
      diagnosed with a pelvic recurrence invading the urinary bladder trigone and the
      rectosigmoid so she was submitted to a total pelvic exenteration. 

PMID- 26305209
TI  - Effects of 2-oxoglutaric acid on bone morphometry, densitometry, mechanics, and
      immunohistochemistry in 9-month-old boars with prenatal dexamethasone-induced
      osteopenia.
AB  - The structural quality of the connective tissue is genetically determined and is
      influenced by hormonal and nutritional modification. An effect of a 2-Ox-rich
      diet on bone mineralization and structure and expression of non-collagenous
      protein in articular and growth cartilages of maternal dexamethasone-treated 9
      month-old boars was considered in this study. Sows were treated i.m. with
      dexamethasone at the dose of 0.03 mg kg(-1) body weight every second day during
      the last 45 days of pregnancy. After the birth, the boars were divided into two
      groups: administered and not supplemented with 2-Ox for 9 months (0.4 g/kg body
      weight/day). Dexamethasone given during the prenatal time inhibited the growth
      and negatively influenced the mechanics, geometry and histomorphometrical
      parameters of long bones and cartilage irrespective of the diet. Moreover,
      maternal dexamethasone treatment resulted in expression of osteocalcin in the
      articular cartilage, and the diet rich in 2-Ox limited the OC expression. This
      study demonstrated that changes observed in adult boars initiated by
      dexamethasone treatment in the prenatal period were persistent and long-term use
      of alimentary 2-Ox supplementation can counteract only some of the destructive
      changes evoked by prenatal dexamethasone excess. 

PMID- 26305210
TI  - The Wheat NAC Transcription Factor TaNAC2L Is Regulated at the Transcriptional
      and Post-Translational Levels and Promotes Heat Stress Tolerance in Transgenic
      Arabidopsis.
AB  - Heat stress poses a serious threat to global crop production. In efforts that aim
      to mitigate the adverse effects of heat stress on crops, a variety of genetic
      tools are being used to develop plants with improved thermotolerance. The
      characterization of important regulators of heat stress tolerance provides
      essential information for this aim. In this study, we examine the wheat (Triticum
      aestivum) NAC transcription factor gene TaNAC2L. High temperature induced TaNAC2L
      expression in wheat and overexpression of TaNAC2L in Arabidopsis thaliana
      enhanced acquired heat tolerance without causing obvious alterations in phenotype
      compared with wild type under normal conditions. TaNAC2L overexpression also
      activated the expression of heat-related genes in the transgenic Arabidopsis
      plants, suggesting that TaNAC2L may improve heat tolerance by regulating the
      expression of stress-responsive genes. Notably, TaNAC2L is also regulated at the
      post-translational level and might be degraded via a proteasome-mediated pathway.
      Thus, this wheat transcription factor may have potential uses in enhancing
      thermotolerance in crops. 

PMID- 26305211
TI  - The Broad Anti-AML Activity of the CD33/CD3 BiTE Antibody Construct, AMG 330, Is
      Impacted by Disease Stage and Risk.
AB  - The CD33/CD3-bispecific T-cell engaging (BiTE) antibody construct, AMG 330,
      potently lyses CD33+ leukemic cells in vitro. Using specimens from 41 patients
      with acute myeloid leukemia (AML), we studied the factors that might contribute
      to clinical response or resistance. For this purpose, thawed aliquots of primary
      AML samples were immunophenotypically characterized and subjected to various
      doses of AMG 330 in the presence or absence of healthy donor T-cells. After 48
      hours, drug-specific cytotoxicity was quantified and correlated with CD33
      expression levels, amounts of T-cells present, and other disease characteristics.
      AMG 330 caused modest cytotoxicity that was correlated with the amount of
      autologous T-cells (P = 0.0001) but not CD33 expression, as AMG 330 exerted
      marked cytotoxic effects in several specimens with minimal CD33 expression. With
      healthy donor T-cells added, AMG 330 cytotoxicity depended on the drug dose and
      effector:target (E:T) cell ratio. High cytotoxic activity was observed even with
      minimal CD33 expression, and AMG 330 cytotoxicity and CD33 expression correlated
      only at high E:T cell ratio and high AMG 330 doses (P<0.003). AMG 330 resulted in
      significantly higher cytotoxicity in specimens from patients with newly diagnosed
      AML than those with relapsed/refractory disease despite similar levels of CD33 on
      myeloblasts. AMG 330 cytotoxicity also appeared greater in specimens from
      patients with favorable-risk disease as compared to other specimens. Together,
      our data demonstrate that AMG 330 is highly active in primary AML specimens
      across the entire disease spectrum, while suggesting the presence of yet
      undefined, CD33-independent, relative resistance mechanisms in specific patient
      subsets. 

PMID- 26305212
TI  - Hybrid random walk-linear discriminant analysis method for unwrapping
      quantitative phase microscopy images of biological samples.
AB  - Standard algorithms for phase unwrapping often fail for interferometric
      quantitative phase imaging (QPI) of biological samples due to the variable
      morphology of these samples and the requirement to image at low light intensities
      to avoid phototoxicity. We describe a new algorithm combining random walk-based
      image segmentation with linear discriminant analysis (LDA)-based feature
      detection, using assumptions about the morphology of biological samples to
      account for phase ambiguities when standard methods have failed. We present three
      versions of our method: first, a method for LDA image segmentation based on a
      manually compiled training dataset; second, a method using a random walker (RW)
      algorithm informed by the assumed properties of a biological phase image; and
      third, an algorithm which combines LDA-based edge detection with an efficient RW
      algorithm. We show that the combination of LDA plus the RW algorithm gives the
      best overall performance with little speed penalty compared to LDA alone, and
      that this algorithm can be further optimized using a genetic algorithm to yield
      superior performance for phase unwrapping of QPI data from biological samples.

PMID- 26305213
TI  - Exposure of Neonatal Mice to Tobacco Smoke Disturbs Synaptic Proteins and Spatial
      Learning and Memory from Late Infancy to Early Adulthood.
AB  - Exposure to environmental tobacco smoke (ETS) in the early postnatal period has
      been associated with several diseases; however, little is known about the brain
      effects of ETS exposure during this critical developmental period or the long
      term consequences of this exposure. This study investigated the effects of the
      early postnatal ETS exposure on both reference and working memory, synaptic
      proteins and BDNF from late infancy to early adulthood (P3-P73). BALB/c mice were
      exposed to ETS generated from 3R4F reference research cigarettes (0.73 mg of
      nicotine/cigarette) from P3 to P14. Spatial reference and working memory were
      evaluated in the Morris water maze during infancy (P20-P29), adolescence (P37
      P42) and adulthood (P67-P72). Synapsin, synaptophysin, PSD95 and brain-derived
      neurotrophic factor (BDNF) were assessed at P15, P35 and P65 by
      immunohistochemistry and immunoblotting. Mice that were exposed to ETS during the
      early postnatal period showed poorer performance in the spatial reference memory
      task. Specifically, the ETS-exposed mice exhibited a significantly reduced time
      and distance traveled in the target quadrant and in the platform location area
      than the controls at all ages evaluated. In the spatial working memory task, ETS
      disrupted the maintenance but not the acquisition of the critical spatial
      information in both infancy and adolescence. ETS also induced changes in synaptic
      components, including decreases in synapsin, synaptophysin, PSD95 and BDNF levels
      in the hippocampus. Exposure to ETS in the early postnatal period disrupts both
      spatial reference and working memory; these results may be related to changes in
      synaptogenesis in the hippocampus. Importantly, most of these effects were not
      reversed even after a long exposure-free period. 

PMID- 26305215
TI  - Correction: Characterization of the Newly Isolated Lytic Bacteriophages KTN6 and
      KT28 and Their Efficacy against Pseudomonas aeruginosa Biofilm.

PMID- 26305214
TI  - NDR Kinases Are Essential for Somitogenesis and Cardiac Looping during Mouse
      Embryonic Development.
AB  - Studies of mammalian tissue culture cells indicate that the conserved and
      distinct NDR isoforms, NDR1 and NDR2, play essential cell biological roles.
      However, mice lacking either Ndr1 or Ndr2 alone develop normally. Here, we
      studied the physiological consequences of inactivating both NDR1 and NDR2 in
      mice, showing that the lack of both Ndr1/Ndr2 (called Ndr1/2-double null mutants)
      causes embryonic lethality. In support of compensatory roles for NDR1 and NDR2,
      total protein and activating phosphorylation levels of the remaining NDR isoform
      were elevated in mice lacking either Ndr1 or Ndr2. Mice retaining one single wild
      type Ndr allele were viable and fertile. Ndr1/2-double null embryos displayed
      multiple phenotypes causing a developmental delay from embryonic day E8.5
      onwards. While NDR kinases are not required for notochord formation, the somites
      of Ndr1/2-double null embryos were smaller, irregularly shaped and unevenly
      spaced along the anterior-posterior axis. Genes implicated in somitogenesis were
      down-regulated and the normally symmetric expression of Lunatic fringe, a
      component of the Notch pathway, showed a left-right bias in the last forming
      somite in 50% of all Ndr1/2-double null embryos. In addition, Ndr1/2-double null
      embryos developed a heart defect that manifests itself as pericardial edemas,
      obstructed heart tubes and arrest of cardiac looping. The resulting cardiac
      insufficiency is the likely cause of the lethality of Ndr1/2-double null embryos
      around E10. Taken together, we show that NDR kinases compensate for each other in
      vivo in mouse embryos, explaining why mice deficient for either Ndr1 or Ndr2 are
      viable. Ndr1/2-double null embryos show defects in somitogenesis and cardiac
      looping, which reveals their essential functions and shows that the NDR kinases
      are critically required during the early phase of organogenesis. 

PMID- 26305216
TI  - Increased Blood-Reelin-Levels in First Episode Schizophrenia.
AB  - BACKGROUND: Reelin is an extracellular glycoprotein involved in several functions
      of brain development, synaptogenesis and dendritic proliferation. Numerous
      studies found perturbation in the reelin system and altered serum reelin levels
      in neuropsychiatric patients using the western blot procedure. In the
      international literature, this is the first study that made use of an enzyme
      linked immunosorbent assay to analyze serum reelin protein concentration
      quantitatively. RATIONALE: In order to study possible alterations in reelin blood
      levels in schizophrenia, we analyzed this signal in schizophrenic patients with a
      first episode hallucinatory and paranoid syndrome and control subjects in a pilot
      study design. RESULTS: We found increased blood reelin protein concentration in
      schizophrenic patients compared to healthy controls. DISCUSSION: Our findings
      point to a relevant role of reelin metabolism in the pathogenesis of
      schizophrenia.Reelin could be a biomarker for the course of disease or
      psychopharmacological treatment. CONCLUSION: We conclude that the reelin protein
      blood concentration might be a relevant signal with respect to the
      pathophysiology of schizophrenia.

PMID- 26305217
TI  - Direct Renin Inhibition with Aliskiren Improves Ischemia-Induced
      Neovasculogenesis in Diabetic Animals via the SDF-1 Related Mechanism.
AB  - OBJECTIVE: Aliskiren is a direct renin inhibitor which is suggested to modify
      proangiogenic cells in addition to lower blood pressure. Given that angiogenesis
      is impaired in the presence of diabetes mellitus, we would like to investigate
      whether and how aliskiren enhances endothelial progenitor cells (EPCs) and
      improves ischemic-induced neovasculogenesis by an effect independent of blood
      pressure reduction in diabetic animals. METHODS: Streptozotocin-induced diabetic
      mice were administered with either aliskiren (5 or 25 mg/kg/day) using an osmotic
      pump or hydralazine (2 or 10 mg/kg/day) given in drinking water for two weeks
      prior to a hind-limb ischemia surgery. Laser Doppler imaging and flow cytometry
      were used to evaluate the degree of neovasculogenesis and the circulating levels
      of EPCs, respectively. RESULTS: In streptozotocin-induced diabetic mice,
      aliskiren enhanced the recovery of limb perfusion and capillary density,
      increased the number of circulating Sca-1+/Flk-1+ EPC-like cells, and elevated
      the levels of the plasma vascular endothelial growth factor (VEGF) and stromal
      cell-derived factor (SDF)-1alpha in a dose-dependent manner, whereas there were
      no such effects in hydralazine-treated mice. Intraperitoneal administration of
      anti-SDF-1 neutralizing monoclonal antibodies abolished the effects of aliskiren.
      CONCLUSIONS: Independent of the reduction of blood pressure, aliskiren enhanced
      ischemia-induced neovasculogenesis in a dose-dependent manner via VEGF/SDF-1alpha
      related mechanisms in diabetic mice.

PMID- 26305219
TI  - Residential Exposure to Road and Railway Noise and Risk of Prostate Cancer: A
      Prospective Cohort Study.
AB  - BACKGROUND: Few modifiable risk factors for prostate cancer are known. Recently,
      disruption of the circadian system has been proposed to affect risk, as it
      entails an inhibited melatonin production, and melatonin has demonstrated
      beneficial effects on cancer inhibition. This suggests a potential role of
      traffic noise in prostate cancer. METHODS: Road traffic and railway noise was
      calculated for all present and historical addresses from 1987-2010 for a cohort
      of 24,473 middle-aged, Danish men. During follow-up, 1,457 prostate cancer cases
      were identified. We used Cox Proportional Hazards Models to calculate the
      association between noise exposure and incident prostate cancer. Incidence Rate
      Ratios (IRR) were calculated as crude and adjusted for smoking status, education,
      socioeconomic position, BMI, waist circumference, physical activity, calendar
      year, and traffic noise from other sources than the one investigated. RESULTS:
      There was no association between residential road traffic noise and risk of
      prostate cancer for any of the three exposure windows: 1, 5 or 10-year mean noise
      exposure before prostate cancer diagnosis. This result persisted when stratifying
      cases by aggressiveness. For railway noise, there was no association with overall
      prostate cancer. There was no statistically significant effect modification by
      age, education, smoking status, waist circumference or railway noise, on the
      association between road traffic noise and prostate cancer, although there seemed
      to be a suggestion of an association among never smokers (IRR: 1.16; 95% CI: 1.00
      1.36). CONCLUSION: The present study does not support an overall association
      between either railway or road traffic noise and overall prostate cancer.

PMID- 26305218
TI  - Lymphangiogenic Markers and Their Impact on Nodal Metastasis and Survival in Non
      Small Cell Lung Cancer--A Structured Review with Meta-Analysis.
AB  - BACKGROUND: In non-small cell lung cancer (NSCLC), nodal metastasis is an adverse
      prognostic factor. Several mediating factors have been implied in the development
      of nodal metastases and investigated for predictive and prognostic properties in
      NSCLC. However, study results differ. In this structured review and meta-analysis
      we explore the published literature on commonly recognized pathways for molecular
      regulation of lymphatic metastasis in NSCLC. METHODS: A structured PubMed search
      was conducted for papers reporting on the expression of known markers of
      lymhangiogenesis in NSCLC patients. Papers of sufficient quality, presenting
      survival and/or correlation data were included. RESULTS: High levels of vascular
      endothelial growth factor C (VEGF-C, HR 1.57 95% CI 1.34-1.84) and high lymphatic
      vascular density (LVD, HR 1.84 95% CI 1.18-2.87) were significant prognostic
      markers of poor survival and high expression of VEGF-C, vascular endothelial
      growth factor receptor 3 (VEGFR3) and LVD was associated with lymph node
      metastasis in NSCLC. CONCLUSION: Lymphangiogenic markers are prognosticators of
      survival and correlate with lymph node metastasis in NSCLC. Their exact role and
      clinical implications should be further elucidated.

PMID- 26305221
TI  - Adaptive Responses Limited by Intrinsic Noise.
AB  - Sensory systems have mechanisms to respond to the external environment and adapt
      to them. Such adaptive responses are effective for a wide dynamic range of
      sensing and perception of temporal change in stimulus. However, noise generated
      by the adaptation system itself as well as extrinsic noise in sensory inputs may
      impose a limit on the ability of adaptation systems. The relation between
      response and noise is well understood for equilibrium systems in the form of
      fluctuation response relation. However, the relation for nonequilibrium systems,
      including adaptive systems, are poorly understood. Here, we systematically
      explore such a relation between response and fluctuation in adaptation systems.
      We study the two network motifs, incoherent feedforward loops (iFFL) and negative
      feedback loops (nFBL), that can achieve perfect adaptation. We find that the
      response magnitude in adaption systems is limited by its intrinsic noise,
      implying that higher response would have higher noise component as well.
      Comparing the relation of response and noise in iFFL and nFBL, we show that
      whereas iFFL exhibits adaptation over a wider parameter range, nFBL offers higher
      response to noise ratio than iFFL. We also identify the condition that yields the
      upper limit of response for both network motifs. These results may explain the
      reason of why nFBL seems to be more abundant in nature for the implementation of
      adaption systems. 

PMID- 26305222
TI  - What Comes First, Job Burnout or Secondary Traumatic Stress? Findings from Two
      Longitudinal Studies from the U.S. and Poland.
AB  - This longitudinal research examined the directions of the relationships between
      job burnout and secondary traumatic stress (STS) among human services workers. In
      particular, using cross-lagged panel design, we investigated whether job burnout
      predicts STS at 6-month follow up or whether the level of STS symptoms explains
      job burnout at 6-month follow-up. Participants in Study 1 were behavioral or
      mental healthcare providers (N = 135) working with U.S. military personnel
      suffering from trauma. Participants in Study 2 were healthcare providers, social
      workers, and other human services professions (N = 194) providing various types
      of services for civilian trauma survivors in Poland. The cross-lagged analyses
      showed consistent results for both longitudinal studies; job burnout measured at
      Time 1 led to STS at Time 2, but STS assessed at Time 1 did not lead to job
      burnout at Time 2. These results contribute to a discussion on the origins of STS
      and job burnout among human services personnel working in highly demanding
      context of work-related secondary exposure to traumatic events and confirm that
      job burnout contributes to the development of STS. 

PMID- 26305223
TI  - MRPack: Multi-Algorithm Execution Using Compute-Intensive Approach in MapReduce.
AB  - Large quantities of data have been generated from multiple sources at exponential
      rates in the last few years. These data are generated at high velocity as real
      time and streaming data in variety of formats. These characteristics give rise to
      challenges in its modeling, computation, and processing. Hadoop MapReduce (MR) is
      a well known data-intensive distributed processing framework using the
      distributed file system (DFS) for Big Data. Current implementations of MR only
      support execution of a single algorithm in the entire Hadoop cluster. In this
      paper, we propose MapReducePack (MRPack), a variation of MR that supports
      execution of a set of related algorithms in a single MR job. We exploit the
      computational capability of a cluster by increasing the compute-intensiveness of
      MapReduce while maintaining its data-intensive approach. It uses the available
      computing resources by dynamically managing the task assignment and intermediate
      data. Intermediate data from multiple algorithms are managed using multi-key and
      skew mitigation strategies. The performance study of the proposed system shows
      that it is time, I/O, and memory efficient compared to the default MapReduce. The
      proposed approach reduces the execution time by 200% with an approximate 50%
      decrease in I/O cost. Complexity and qualitative results analysis shows
      significant performance improvement. 

PMID- 26305224
TI  - Human Blood and Mucosal Regulatory T Cells Express Activation Markers and
      Inhibitory Receptors in Inflammatory Bowel Disease.
AB  - BACKGROUND: FOXP3+ regulatory T cells (Tregs) are critical for preventing
      intestinal inflammation. However, FOXP3+ T cells are paradoxically increased in
      the intestines of patients with the inflammatory bowel disease (IBD) ulcerative
      colitis (UC) or Crohn's disease (CD). We determined whether these FOXP3+ cells in
      IBD patients share or lack the phenotype of such cells from patients without IBD.
      METHODS: We quantified and characterized FOXP3+ Treg populations, as well as
      FOXP3- CD4+ T cells, in the lamina propria lymphocytes (LPL) of intestine
      surgically resected from patients with and without IBD, and in the blood of
      controls or Crohn's patients with or without disease activity. RESULTS: In all
      samples, a similar fraction of FOXP3+ cells expressed the "natural" Treg (nTreg)
      marker Helios, suggesting that, in IBD, these cells are not entirely "induced"
      Tregs (iTregs) derived from activated effector T cells. Helios+ and Helios-
      FOXP3+ T cells demonstrated similar expression of maturation markers, activation
      markers, and inhibitory molecules between IBD patients and controls, while FOXP3-
      cells paradoxically expressed more of the inhibitory receptors CD39, CTLA4, and
      PD-1 in inflamed mucosa. Greater expression of activation markers was also seen
      in both Helios+ and Helios- Tregs, relative to FOXP3- cells, in both IBD patients
      and controls, indicating that Tregs are effectively activated by antigen in IBD.
      CONCLUSIONS: Extensive immunophenotyping revealed that Helios+ and Helios-
      mucosal Tregs exist at a similar frequency, and have a similar expression of
      inhibitory molecules and activation markers in patients with IBD as in healthy
      controls.

PMID- 26305225
TI  - Nucleosome Organization in Human Embryonic Stem Cells.
AB  - The fundamental repeating unit of eukaryotic chromatin is the nucleosome. Besides
      being involved in packaging DNA, nucleosome organization plays an important role
      in transcriptional regulation and cellular identity. Currently, there is much
      debate about the major determinants of the nucleosome architecture of a genome
      and its significance with little being known about its role in stem cells. To
      address these questions, we performed ultra-deep sequencing of nucleosomal DNA in
      two human embryonic stem cell lines and integrated our data with numerous
      epigenomic maps. Our analyses have revealed that the genome is a determinant of
      nucleosome organization with transcriptionally inactive regions characterized by
      a "ground state" of nucleosome profiles driven by underlying DNA sequences. DNA
      sequence preferences are associated with heterogeneous chromatin organization
      around transcription start sites. Transcription, histone modifications, and DNA
      methylation alter this "ground state" by having distinct effects on both
      nucleosome positioning and occupancy. As the transcriptional rate increases,
      nucleosomes become better positioned. Exons transcribed and included in the final
      spliced mRNA have distinct nucleosome profiles in comparison to exons not
      included at exon-exon junctions. Genes marked by the active modification H3K4m3
      are characterized by lower nucleosome occupancy before the transcription start
      site compared to genes marked by the inactive modification H3K27m3, while
      bivalent domains, genes associated with both marks, lie exactly in the middle.
      Combinatorial patterns of epigenetic marks (chromatin states) are associated with
      unique nucleosome profiles. Nucleosome organization varies around transcription
      factor binding in enhancers versus promoters. DNA methylation is associated with
      increasing nucleosome occupancy and different types of methylations have distinct
      location preferences within the nucleosome core particle. Finally, computational
      analysis of nucleosome organization alone is sufficient to elucidate much of the
      circuitry of pluripotency. Our results, suggest that nucleosome organization is
      associated with numerous genomic and epigenomic processes and can be used to
      elucidate cellular identity. 

PMID- 26305226
TI  - The Impact of a One-Dose versus Two-Dose Oral Cholera Vaccine Regimen in Outbreak
      Settings: A Modeling Study.
AB  - BACKGROUND: In 2013, a stockpile of oral cholera vaccine (OCV) was created for
      use in outbreak response, but vaccine availability remains severely limited.
      Innovative strategies are needed to maximize the health impact and minimize the
      logistical barriers to using available vaccine. Here we ask under what conditions
      the use of one dose rather than the internationally licensed two-dose protocol
      may do both. METHODS AND FINDINGS: Using mathematical models we determined the
      minimum relative single-dose efficacy (MRSE) at which single-dose reactive
      campaigns are expected to be as or more effective than two-dose campaigns with
      the same amount of vaccine. Average one- and two-dose OCV effectiveness was
      estimated from published literature and compared to the MRSE. Results were
      applied to recent outbreaks in Haiti, Zimbabwe, and Guinea using stochastic
      simulations to illustrate the potential impact of one- and two-dose campaigns. At
      the start of an epidemic, a single dose must be 35%-56% as efficacious as two
      doses to avert the same number of cases with a fixed amount of vaccine (i.e.,
      MRSE between 35% and 56%). This threshold decreases as vaccination is delayed.
      Short-term OCV effectiveness is estimated to be 77% (95% CI 57%-88%) for two
      doses and 44% (95% CI -27% to 76%) for one dose. This results in a one-dose
      relative efficacy estimate of 57% (interquartile range 13%-88%), which is above
      conservative MRSE estimates. Using our best estimates of one- and two-dose
      efficacy, we projected that a single-dose reactive campaign could have prevented
      70,584 (95% prediction interval [PI] 55,943-86,205) cases in Zimbabwe, 78,317
      (95% PI 57,435-100,150) in Port-au-Prince, Haiti, and 2,826 (95% PI 2,490-3,170)
      cases in Conakry, Guinea: 1.1 to 1.2 times as many as a two-dose campaign. While
      extensive sensitivity analyses were performed, our projections of cases averted
      in past epidemics are based on severely limited single-dose efficacy data and may
      not fully capture uncertainty due to imperfect surveillance data and uncertainty
      about the transmission dynamics of cholera in each setting. CONCLUSIONS: Reactive
      vaccination campaigns using a single dose of OCV may avert more cases and deaths
      than a standard two-dose campaign when vaccine supplies are limited, while at the
      same time reducing logistical complexity. These findings should motivate
      consideration of the trade-offs between one- and two-dose campaigns in resource
      constrained settings, though further field efficacy data are needed and should be
      a priority in any one-dose campaign.

PMID- 26305227
TI  - Systems Genetics Reveals the Functional Context of PCOS Loci and Identifies
      Genetic and Molecular Mechanisms of Disease Heterogeneity.
AB  - Genome wide association studies (GWAS) have revealed 11 independent risk loci for
      polycystic ovary syndrome (PCOS), a common disorder in young women characterized
      by androgen excess and oligomenorrhea. To put these risk loci and the single
      nucleotide polymorphisms (SNPs) therein into functional context, we measured DNA
      methylation and gene expression in subcutaneous adipose tissue biopsies to
      identify PCOS-specific alterations. Two genes from the LHCGR region, STON1
      GTF2A1L and LHCGR, were overexpressed in PCOS. In analysis stratified by obesity,
      LHCGR was overexpressed only in non-obese PCOS women. Although not differentially
      expressed in the entire PCOS group, INSR was underexpressed in obese PCOS
      subjects only. Alterations in gene expression in the LHCGR, RAB5B and INSR
      regions suggest that SNPs in these loci may be functional and could affect gene
      expression directly or indirectly via epigenetic alterations. We identified
      reduced methylation in the LHCGR locus and increased methylation in the INSR
      locus, changes that are concordant with the altered gene expression profiles.
      Complex patterns of meQTL and eQTL were identified in these loci, suggesting that
      local genetic variation plays an important role in gene regulation. We propose
      that non-obese PCOS women possess significant alterations in LH receptor
      expression, which drives excess androgen secretion from the ovary. Alternatively,
      obese women with PCOS possess alterations in insulin receptor expression, with
      underexpression in metabolic tissues and overexpression in the ovary, resulting
      in peripheral insulin resistance and excess ovarian androgen production. These
      studies provide a genetic and molecular basis for the reported clinical
      heterogeneity of PCOS. 

PMID- 26305229
TI  - Editorial Comment for White et al.

PMID- 26305228
TI  - Identification of Amino Acids at the Catalytic Site of a Ferredoxin-Dependent
      Cyanobacterial Nitrate Reductase.
AB  - An in silico model of the ferredoxin-dependent nitrate reductase from the
      cyanobacterium Synechococcus sp. PCC 7942, and information about active sites in
      related enzymes, had identified Cys148, Met149, Met306, Asp163, and Arg351 as
      amino acids likely to be involved in either nitrate binding, prosthetic group
      binding, or catalysis. Site-directed mutagenesis was used to alter each of these
      residues, and differences in enzyme activity and substrate binding of the
      purified variants were analyzed. In addition, the effects of these replacements
      on the assembly and properties of the Mo cofactor and [4Fe-4S] centers were
      investigated using Mo and Fe determinations, coupled with electron paramagnetic
      resonance spectroscopy. The C148A, M149A, M306A, D163N, and R351Q variants were
      all inactive with either the physiological electron donor, reduced ferredoxin, or
      the nonphysiological electron donor, reduced methyl viologen, as the source of
      electrons, and all exhibited changes in the properties of the Mo cofactor. Charge
      conserving D163E and R351K variants were also inactive, suggesting that specific
      amino acids are required at these two positions. The implications for the role of
      these five conserved active-site residues in light of these new results and
      previous structural, spectroscopic, and mutagenesis studies for related
      periplasmic nitrate reductases are discussed. 

PMID- 26305230
TI  - Complete mitochondrial genome of the "floppy-wing" morph reproductive termite,
      Reticulitermes labralis (Isoptera: Rhinotermitidae).
AB  - The complete mitochondrial genome of Reticulitermes labralis (Isoptera:
      Rhinotermitidae) was determined for its nucleotide sequence of 16 113 bp. Its
      gene content and organization were identical with other Reticulitermes species.
      The 13 protein-coding genes (PCGs) have typical ATN initiation codon. But, the
      stop codons were TAA, TAG and an incomplete termination codon (T) abutting an
      adjacent tRNA gene. Twenty-two tRNA genes, in addition to tRNASer(AGN) replaced
      lacking of the DHU stem with a simple loop, showed the typical clover-leaf
      secondary structure. The A + T-rich region was 1311 bp in length with 65.98% A +
      T content. In addition to the A + T-rich region, non-coding sequences of the
      mtDNA genome harbored 17 intergenic spacers. There were three complete repeats of
      repeat A in CR, which were not discovered in other termite species. Phylogenetic
      tree based on the 11 complete mitochondrial genome sequences of closely related
      termite species accords well with morphological phylogenetic analysis.

PMID- 26305231
TI  - Total Synthesis of the Galbulimima Alkaloids Himandravine and GB17 Using
      Biomimetic Diels-Alder Reactions of Double Diene Precursors.
AB  - The enantioselective total syntheses of himandravine and GB17 were completed
      through a common biomimetic strategy involving Diels-Alder reactions of unusual
      double diene containing linear precursors. The double diene precursors,
      containing or lacking a C12 substituent as required to produce GB17 or
      himandravine, respectively, were found to undergo Diels-Alder reactions to afford
      mixtures of regioisomeric cycloadducts that map onto the alternative carbocyclic
      frameworks of both himandravine and GB17. Computational investigations revealed
      that these Diels-Alder reactions proceed via transition state structures of
      similar energy that have a high degree of bispericyclic character and that the
      low levels of regioselectivity observed in the reactions are a consequence of
      competing orbital interaction and distortion energies. The combined experimental
      and computational results provide valuable insights into the biosynthesis of the
      Galbulimima alkaloids. 

PMID- 26305232
TI  - Intrafractional 3D localization using kilovoltage digital tomosynthesis for
      sliding-window intensity modulated radiation therapy.
AB  - To implement novel imaging sequences integrated into intensity modulated
      radiation therapy (IMRT) and determine 3D positions for intrafractional patient
      motion monitoring and management.In one method, we converted a static gantry IMRT
      beam into a series of arcs in which dose index and multileaf collimator positions
      for all control points were unchanged, but gantry angles were modified to
      oscillate +/- 3 degrees  around the original angle. Kilovoltage (kV) projections
      were acquired continuously throughout delivery and reconstructed to provide a
      series of 6 degrees  arc digital tomosynthesis (DTS) images which served to
      evaluate the in-plane positions of embedded-fiducials/vertebral-body. To obtain
      out-of-plane positions via triangulation, a 20 degrees  gantry rotation with beam
      hold-off was inserted during delivery to produce a pair of 6 degrees  DTS images
      separated by 14 degrees . In a second method, the gantry remained stationary, but
      both kV source and detector moved over a 15 degrees  longitudinal arc using pitch
      and translational adjustment of the robotic arms. Evaluation of localization
      accuracy in an anthropomorphic Rando phantom during simulated intrafractional
      motion used programmed couch translations from customized scripts. Purpose-built
      software was used to reconstruct DTS images, register them to reference template
      images and calculate 3D fiducial positions.No significant dose difference (<0.5%)
      was found between the original and converted IMRT beams. For a typical
      hypofractionated spine treatment, 200 single DTS (6 degrees  arc) and 10 paired
      DTS (20 degrees  arc) images were acquired for each IMRT beam, providing in-plane
      and out-of-plane monitoring every 1.6 and 34.5 s, respectively. Mean +/- standard
      deviation error in predicted position was -0.3 +/- 0.2 mm, -0.1 +/- 0.1 mm in
      plane, and 0.2 +/- 0.4 mm out-of-plane with rotational gantry, 0.8 +/- 0.1 mm, 
      0.7 +/- 0.3 mm in-plane and 1.1 +/- 0.1 mm out-of-plane with translational
      source/detector.Acquiring 3D fiducial positions from kV-DTS during fixed gantry
      IMRT is technically feasible, and is capable of providing reliable guidance for
      intrafractional patient motion management.

PMID- 26305233
TI  - Detecting and classifying movement-related cortical potentials associated with
      hand movements in healthy subjects and stroke patients from single-electrode,
      single-trial EEG.
AB  - OBJECTIVE: To detect movement intention from executed and imaginary palmar grasps
      in healthy subjects and attempted executions in stroke patients using one EEG
      channel. Moreover, movement force and speed were also decoded. APPROACH: Fifteen
      healthy subjects performed motor execution and imagination of four types of
      palmar grasps. In addition, five stroke patients attempted to perform the same
      movements. The movements were detected from the continuous EEG using a single
      electrode/channel overlying the cortical representation of the hand. Four
      features were extracted from the EEG signal and classified with a support vector
      machine (SVM) to decode the level of force and speed associated with the
      movement. The system performance was evaluated based on both detection and
      classification. MAIN RESULTS: ~ 75% of all movements (executed, imaginary and
      attempted) were detected 100 ms before the onset of the movement. ~ 60% of the
      movements were correctly classified according to the intended level of force and
      speed. When detection and classification were combined, ~ 45% of the movements
      were correctly detected and classified in both the healthy and stroke subjects,
      although the performance was slightly better in healthy subjects. SIGNIFICANCE:
      The results indicate that it is possible to use a single EEG channel for
      detecting movement intentions that may be combined with assistive technologies.
      The simple setup may lead to a smoother transition from laboratory tests to the
      clinic.

PMID- 26305234
TI  - Enhanced Cyclability of Li/Polysulfide Batteries by a Polymer-Modified Carbon
      Paper Current Collector.
AB  - Lithium-sulfur (Li-S) batteries are considered to be the next-generation
      rechargeable systems due to their high energy densities and low cost. However,
      significant capacity decay over cycling is a major impediment for their practical
      applications. Polysulfides Li2Sx (3<x<=8) formed in the cycling are soluble in
      liquid electrolyte, which is the main reason for capacity loss and cycling
      instability. Functional polymers can tune the structure and property of sulfur
      electrodes, hold polysulfides, and improve cycle life. Herein, we examine a
      polyvinylpyrrolidone-modified carbon paper (CP-PVP) current collector in
      Li/polysulfide cells. PVP is soluble in the electrolyte solvent, but shows strong
      affinity with lithium polysulfides. The retention of polysulfides in the CP-PVP
      current collector is improved by ~50%, which is measured by a linear sweep
      voltammetry method. Without LiNO3 additive in the electrolyte, the CP-PVP current
      collector with 50 MUg of PVP can significantly improve cycling stability with a
      capacity retention of >90% over 50 cycles at C/10 rate. With LiNO3 additive in
      the electrolyte, the cell shows a reversible capacity of >1000 mAh g(-1) and a
      capacity retention of >80% over 100 cycles at C/5 rate.

PMID- 26305235
TI  - The Activation of Complement and Its Role in the Pathogenesis of Thromboembolism.
AB  - It is well established that inflammation and thrombosis are intricately linked
      processes, and there is increasing evidence of the importance of their roles in
      activated complement in the pathogenesis of thromboembolism. The two systems are
      activated by similar stimuli simultaneously and interact, either directly or
      through biochemical mediators, to protect the host from microbial invasion.
      Diseases characterized by complement hyperactivity such as paroxysmal nocturnal
      hemoglobinuria and atypical hemolytic uremic syndrome have high rates of
      thrombosis. This review describes how disease processes where there is excessive
      complement activation leads to thrombosis, and the specific interactions between
      the complement and coagulation systems that lead to pathological thrombus
      formation. 

PMID- 26305236
TI  - Thrombosis and Hemorrhage in Diabetic Retinopathy: A Perspective from an
      Inflammatory Standpoint.
AB  - Retinal ischemia and hemorrhage are hallmarks of worsening diabetic retinopathy,
      which can lead to neovascularization, macular edema, and severe vision loss.
      Although diabetes alters expression of clotting factors and their activities, and
      increases retinal microthromboses, the effects of thrombotic processes on the
      pathogenesis of diabetic retinopathy are not fully understood. In addition to the
      roles of coagulation and fibrinolytic cascades in thrombosis and hemostasis,
      components in these systems also mediate multiple effects on the vasculature that
      promote inflammation. Plasma kallikrein, thrombin, and urokinase are increased in
      diabetic retinopathy, and exert proinflammatory effects that contribute to
      retinal vascular dysfunction. The accumulation and activation of these and
      additional coagulation factors in the vitreous due to hemorrhage and chronic
      retinal injury in the diabetic retina may contribute to worsening of retinal
      inflammation and capillary dysfunction, which lead to retinal ischemia and edema.
      Further understanding of the role for specific coagulation factors in diabetic
      retinopathy may suggest new therapeutic opportunities for this vision-threatening
      disease. 

PMID- 26305237
TI  - Coagulopathy of Acute Sepsis.
AB  - Coagulopathy is common in acute sepsis and may range from subclinical activation
      of blood coagulation (hypercoagulability), which may contribute to venous
      thromboembolism, to acute disseminated intravascular coagulation, characterized
      by widespread microvascular thrombosis and consumption of platelets and
      coagulation proteins, eventually causing bleeding. The key event underlying this
      life-threatening complication is the overwhelming inflammatory host response to
      the pathogen leading to the overexpression of inflammatory mediators. The latter,
      along with the microorganism and its derivatives drive the major changes
      responsible for massive thrombin formation and fibrin deposition: (1) aberrant
      expression of tissue factor mainly by monocytes-macrophages, (2) impairment of
      anticoagulant pathways, orchestrated by dysfunctional endothelial cells (ECs),
      and (3) suppression of fibrinolysis because of the overproduction of plasminogen
      activator inhibitor-1 by ECs and thrombin-mediated activation of thrombin
      activatable fibrinolysis inhibitor. Neutrophils and other cells, upon activation
      or death, release nuclear materials (neutrophil extracellular traps and/or their
      components such as histones, DNA, lysosomal enzymes, and High Mobility Group Box
      1), which have toxic, proinflammatory and prothrombotic properties thus
      contributing to clotting dysregulation. The ensuing microvascular thrombosis
      ischemia significantly contributes to tissue injury and multiple organ
      dysfunction syndromes. These insights into the pathogenesis of sepsis-associated
      coagulopathy may have implications for the development of new diagnostic and
      therapeutic tools. 

PMID- 26305238
TI  - Interplay of Inflammation and Endothelial Dysfunction in Bone Marrow
      Transplantation: Focus on Hepatic Veno-Occlusive Disease.
AB  - Endothelial cells are unique multifunctional cells with basal and inducible
      metabolic and synthetic functions. Various stimuli can induce physiological or
      pathological changes in endothelial cell biology. Hematopoietic stem cell
      transplantation (HSCT) requires high-dose irradiation and/or chemotherapy and is
      associated with increased risk of bacterial infections and immune reactions.
      These factors can affect endothelial cells. This review provides an overview of
      the effects of HSCT on endothelial cells, based on findings observed in cultured
      cells as well as in patients. We first describe to what extent irradiation and
      chemotherapy constitute direct and indirect triggers for endothelial cell
      activation and injury. Then, we highlight the role of the endothelium in several
      complications of HSCT, including capillary leak syndrome, engraftment syndrome,
      transplant-associated microangiopathy, graft-versus-host disease, and diffuse
      alveolar hemorrhages. We also analyze in detail available data on sinusoidal
      obstruction syndrome, previously known as veno-occlusive disease of the liver,
      where liver sinusoidal endothelial cells are first injured and eventually lead to
      sinusoid occlusion and liver cell damage. Finally, we open the question of the
      possible contribution of endothelial damage to cardiovascular events occurring
      long after HSCT. 

PMID- 26305240
TI  - Acceptability and Potential Efficacy of Single-Sex After-School Activity Programs
      for Overweight and At-Risk Children: The Wollongong SPORT RCT.
AB  - OBJECTIVES: Single sex after-school physical activity programs show potential to
      prevent unhealthy weight gain. The aim of this study was to assess the
      acceptability and potential efficacy of single-sex after-school physical activity
      programs for overweight and at-risk children from low-income communities. DESIGN:
      7-month, 2-arm parallel-group, RCT, conducted at an elementary school in a
      disadvantaged area in Wollongong, Australia (March-November 2010). METHODS: 20
      boys and 17 girls were randomized to intervention (PA) or active comparison
      groups (HL). Primary outcomes included implementation, acceptability, percentage
      body fat and BMI z-score. RESULTS: The PA programs were acceptable with high
      implementation and enjoyment rates. At 7 months postintervention girls in the PA
      group displayed greater changes in percentage body fat (adjust diff. = -1.70,
      [95% CI -3.25, -0.14]; d = -0.83) and BMI z-score (-0.19 [-0.36, -0.03]; d= 
      1.00). At 7 months boys in the PA group showed greater changes in waist
      circumference (-3.87 cm [-7.80, 0.15]; d= -0.90) and waist circumference z-score
      (-0.33 [-0.64, -0.03]; d= -0.98). For both boys' and girls' PA groups, changes in
      adiposity were not maintained at 12-month follow-up. CONCLUSIONS: Single-sex
      after-school physical activity programs are acceptable and potentially
      efficacious in preventing unhealthy weight gain among overweight and at-risk
      children. However improvements are hard to sustain once programs finish
      operating.

PMID- 26305239
TI  - Fluorescence Turn-On Folding Sensor To Monitor Proteome Stress in Live Cells.
AB  - Proteome misfolding and/or aggregation, caused by a thermal perturbation or a
      related stress, transiently challenges the cellular protein homeostasis
      (proteostasis) network capacity of cells by consuming chaperone/chaperonin
      pathway and degradation pathway capacity. Developing protein client-based probes
      to quantify the cellular proteostasis network capacity in real time is highly
      desirable. Herein we introduce a small-molecule-regulated fluorescent protein
      folding sensor based on a thermo-labile mutant of the de novo designed
      retroaldolase (RA) enzyme. Since RA enzyme activity is not present in any cell,
      the protein folding sensor is bioorthogonal. The fluorogenic small molecule was
      designed to become fluorescent when it binds to and covalently reacts with folded
      and functional RA. Thus, in the first experimental paradigm, cellular
      proteostasis network capacity and its dynamics are reflected by RA-small molecule
      conjugate fluorescence, which correlates with the amount of folded and functional
      RA present, provided that pharmacologic chaperoning is minimized. In the second
      experimental scenario, the RA-fluorogenic probe conjugate is pre-formed in a cell
      by simply adding the fluorogenic probe to the cell culture media. Unreacted probe
      is then washed away before a proteome misfolding stress is applied in a pulse
      chase-type experiment. Insufficient proteostasis network capacity is reflected by
      aggregate formation of the fluorescent RA-fluorogenic probe conjugate. Removal of
      the stress results in apparent RA-fluorogenic probe conjugate re-folding,
      mediated in part by the heat-shock response transcriptional program augmenting
      cytosolic proteostasis network capacity, and in part by time-dependent RA
      fluorogenic probe conjugate degradation by cellular proteolysis. 

PMID- 26305241
TI  - Phenyllactic Acid from Lactobacillus plantarum PromotesAdipogenic Activity in 3T3
      L1 Adipocyte via Up-Regulationof PPAR-gamma2.
AB  - Synthetic drugs are commonly used to cure various human ailments at present.
      However, the uses of synthetic drugs are strictly regulated because of their
      adverse effects. Thus, naturally occurring molecules may be more suitable for
      curing disease without unfavorable effects. Therefore, we investigated
      phenyllactic acid (PLA) from Lactobacillus plantarum with respect to its effects
      on adipogenic genes and their protein expression in 3T3-L1 pre-adipocytes by qPCR
      and western blot techniques. PLA enhanced differentiation and lipid accumulation
      in 3T3-L1 cells at the concentrations of 25, 50, and 100 MUM. Maximum
      differentiation and lipid accumulation were observed at a concentration of 100
      MUM of PLA, as compared with control adipocytes (p < 0.05). The mRNA and protein
      expression of PPAR-gamma2, C/EBP-alpha, adiponectin, fatty acid synthase (FAS),
      and SREBP-1 were increased by PLA treatment as compared with control adipocytes
      (p < 0.05). PLA stimulates PPAR-gamma mRNA expression in a concentration
      dependent manner, but this expression was lesser than agonist (2.83 +/- 0.014
      fold) of PPAR-gamma2. Moreover, PLA supplementation enhances glucose uptake in
      3T3-L1 pre-adipocytes (11.81 +/- 0.17 mM) compared to control adipocytes, but
      this glucose uptake was lesser than that induced by troglitazone (13.75 +/- 0.95
      mM) and insulin treatment (15.49 +/- 0.20 mM). Hence, we conclude that PLA
      treatment enhances adipocyte differentiation and glucose uptake via activation of
      PPAR-gamma2, and PLA may thus be the potential candidate for preventing Type 2
      Diabetes Mellitus (T2DM). 

PMID- 26305242
TI  - Structure-Activity Relationships of the Antitumor C5-Curcuminoid GO-Y030.
AB  - 1,5-Bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one (2) was isolated from
      Curcuma domestica as a curcumin (1)-related compound, which we named C5-curcumin.
      Intrigued by the potent antitumor activity of C5-curcumin (2)-related 1,5-bisaryl
      1,4-pentadiene-3-ones [bis(arylmethylidene)acetones, termed C5-curcuminoids], we
      previously conducted a structure-activity relationship study of C5-curcuminoids
      and showed that highly active GO-Y030 [1,5-bis(3,5-bis(methoxymethoxy)phenyl)-1,4
      pentadiene-3-one (4)] is the most promising antitumor compound. In this study, a
      panel of C5-curcuminoids based on GO-Y030, consisting of 30 new and 10 known
      compounds, was synthesized to elucidate in detail which moiety of GO-Y030 is
      significant for antitumor activity. The results confirmed that both the cross
      conjugated dienone moiety and the 3,5-bis(methoxymethoxy) substituent are
      important for the antitumor activity. 

PMID- 26305243
TI  - The Potential Use of Natural and Structural Analogues of Antimicrobial Peptides
      in the Fight against Neglected Tropical Diseases.
AB  - Recently, research into the development of new antimicrobial agents has been
      driven by the increase in resistance to traditional antibiotics and Emerging
      Infectious Diseases. Antimicrobial peptides (AMPs) are promising candidates as
      alternatives to current antibiotics in the treatment and prevention of microbial
      infections. AMPs are produced by all known living species, displaying direct
      antimicrobial killing activity and playing an important role in innate immunity.
      To date, more than 2000 AMPs have been discovered and many of these exhibit broad
      spectrum antibacterial, antiviral and anti-parasitic activity. Neglected tropical
      diseases (NTDs) are caused by a variety of pathogens and are particularly wide
      spread in low-income and developing regions of the world. Alternative, cost
      effective treatments are desperately needed to effectively battle these medically
      diverse diseases. AMPs have been shown to be effective against a variety of NTDs,
      including African trypanosomes, leishmaniosis and Chagas disease, trachoma and
      leprosy. In this review, the potential of selected AMPs to successfully treat a
      variety of NTD infections will be critically evaluated. 

PMID- 26305244
TI  - Fatty Acid Profile of Milk and Cheese from Dairy Cows Supplemented a Diet with
      Palm Kernel Cake.
AB  - Lipid supplements (oilseeds vegetables) are included in ruminant diet to increase
      its energy density and improve fatty acid composition of milk and consequently of
      fresh cheese. Milk and cheeses were evaluated from crossbred Holstein * Zebu, fed
      diets enriched with 0%, 25%, 50%, and 75% inclusion levels of palm kernel cake in
      concentrated supplement, which were supplied daily (3.0 kg). Milk and fresh
      cheese (p = 0.001) fatty acids C12:0 exhibited quadratic negative values. Milk
      fatty acids C13:0, C20:0, C18:2t10c12, and C20:2n-6 presented positive quadratic
      values. The milk C18:2n-6 decreased linearly and in fresh cheese exhibited an
      increasing linear effect (p = 0.016). However, the fatty acids grouped in milk
      fat were not affected. The medium-chain fatty acids varied negatively and
      quadratically (p = 0.045). There was no effect on milk and fresh cheese chemical
      composition (p > 0.05). The milk fat was increased (p = 0.0065) quadratically
      (minimum point of 24.7%). Thus, the addition of palm kernel cake to cow diets
      negatively altered the fatty acid profile, it raises the percentage of lauric
      (C12) and tridecanoic (C13) acids fat which is not beneficial to human health
      from a nutraceutical perspective, although it did not influence the
      atherogenicity index. 

PMID- 26305245
TI  - Over-Expression of Porcine Myostatin Missense Mutant Leads to A Gender Difference
      in Skeletal Muscle Growth between Transgenic Male and Female Mice.
AB  - Myostatin, a transforming growth factor-beta family member, is a negative
      regulator of skeletal muscle development and growth. Piedmontese cattle breeds
      have a missense mutation, which results in a cysteine to tyrosine substitution in
      the mature myostatin protein (C313Y). This loss-of-function mutation in myostatin
      results in a double-muscled phenotype in cattle. Myostatin propeptide is an
      inhibitor of myostatin activity and is considered a potential agent to stimulate
      muscle growth in livestock. In this study, we generated transgenic mice
      overexpressing porcine myostatin missense mutant (pmMS), C313Y, and wild-type
      porcine myostatin propeptide (ppMS), respectively, to examine their effects on
      muscle growth in mice. Enhanced muscle growth was observed in both pmMS and ppMS
      transgenic female mice and also in ppMS transgenic male mice. However, there was
      no enhanced muscle growth observed in pmMS transgenic male mice. To explore why
      there is such a big difference in muscle growth between pmMS and ppMS transgenic
      male mice, the expression level of androgen receptor (AR) mutant AR45 was
      measured by Western blot. Results indicated that AR45 expression significantly
      increased in pmMS transgenic male mice while it decreased dramatically in ppMS
      transgenic male mice. Our data demonstrate that both pmMS and ppMS act as
      myostatin inhibitors in the regulation of muscle growth, but the effect of pmMS
      in male mice is reversed by an increased AR45 expression. These results provide
      useful insight and basic theory to future studies on improving pork quality by
      genetically manipulating myostatin expression or by regulating myostatin
      activity. 

PMID- 26305246
TI  - Extraction of Peptidoglycan from L. paracasei subp. Paracasei X12 and Its
      Preliminary Mechanisms of Inducing Immunogenic Cell Death in HT-29 Cells.
AB  - L. paracasei subp. paracasei X12 was previously isolated from a Chinese
      traditional fermented cheese with anticancer activities and probiotic potential.
      Herein, the integral peptidoglycan (X12-PG) was extracted by a modified
      trichloroacetic acid (TCA) method. X12-PG contained the four representative amino
      acids Asp, Glu, Ala and Lys, and displayed the similar lysozyme sensitivity, UV
      visible scanning spectrum and molecular weight as the peptidoglycan standard. X12
      PG could induce the production of apoptotic bodies observed by transmission
      electron microscopy (TEM). X12-PG could significantly induced the translocation
      of calreticulin (CRT) and the release of high mobility group box 1 protein
      (HMGB1), the two notable hallmarks of immunogenic cell death (ICD), with the
      endoplastic reticulum (ER) damaged and subsequently intracellular [Ca(2+)]
      elevated. Our findings implied that X12-PG could induce the ICD of HT-29 cells
      through targeting at the ER. The present results may enlighten the prospect of
      probiotics in the prevention of colon cancer. 

PMID- 26305247
TI  - Development of a New Monomer for the Synthesis of Intrinsic Antimicrobial
      Polymers with Enhanced Material Properties.
AB  - The use of biocidal compounds in polymers is steadily increasing because it is
      one solution to the need for safety and hygiene. It is possible to incorporate an
      antimicrobial moiety to a polymer. These polymers are referred to as intrinsic
      antimicrobial. The biocidal action results from contact of the polymer to the
      microorganisms, with no release of active molecules. This is particularly
      important in critical fields like food technology, medicine and ventilation
      technology, where migration or leaching is crucial and undesirable. The isomers N
      (1,1-dimethylethyl)-4-ethenyl-benzenamine and N-(1,1-dimethyl-ethyl)-3-ethenyl
      benzenamine (TBAMS) are novel (Co-)Monomers for intrinsic anti-microbial
      polymers. The secondary amines were prepared and polymerized to the corresponding
      water insoluble polymer. The antimicrobial activity was analyzed by the test
      method JIS Z 2801:2000. Investigations revealed a high antimicrobial activity
      against Staphylococcus aureus and Escherichia coli with a reduction level of >4.5
      log10 units. Furthermore, scanning electron microscopy (SEM) of E. coli. in
      contact with the polymer indicates a bactericidal action which is caused by
      disruption of the bacteria cell membranes, leading to lysis of the cells. 

PMID- 26305248
TI  - Variants of MicroRNA Genes: Gender-Specific Associations with Multiple Sclerosis
      Risk and Severity.
AB  - Multiple sclerosis (MS) is an autoimmune neuro-inflammatory disease arising from
      complex interactions of genetic, epigenetic, and environmental factors.
      Variations in genes of some microRNAs--key post-transcriptional regulators of
      many genes--can influence microRNAs expression/function and contribute to MS via
      expression changes of protein-coding target mRNA genes. We performed an
      association study of polymorphous variants of MIR146A rs2910164, MIR196A2
      rs11614913, MIR499A rs3746444 MIR223 rs1044165 and their combinations with MS
      risk and severity. 561 unrelated patients with bout-onset MS and 441 healthy
      volunteers were enrolled in the study. We observed associations of MS risk with
      allele MIR223*T and combination (MIR223*T + MIR146A*G/G) carriage in the entire
      groups and in women at Bonferroni-corrected significance level (pcorr < 0.05).
      Besides, MIR146A*G/G association with MS was observed in women with nominal
      significance (pf = 0.025). No MS associations were found in men. A more severe MS
      course (MSSS value > 3.5) was associated with the carriage of MIR499A*C/T and,
      less reliably, of MIR499A*C (pcorr = 0.006 and pcorr = 0.024, respectively) and
      with the carriage of combinations (MIR499A*C/T + MIR196A2*C) and (MIR499A*C +
      MIR196A2*C) (pcorr = 0.00078 and pcorr = 0.0059, respectively). These
      associations also showed gender specificity, as they were not significant in men
      and substantially reinforced in women. The strongest association with MS severity
      was observed in women for combination (MIR499A*C/T + MIR196A2*C): pcorr = 4.43 *
      10(-6) and OR = 3.23 (CI: 1.99-5.26).

PMID- 26305249
TI  - A Futile Redox Cycle Involving Neuroglobin Observed at Physiological Temperature.
AB  - Previous studies identifying the potential anti-apoptotic role of neuroglobin
      raise the question as to how cells might employ neuroglobin to avoid the
      apoptotic impact of acute hypoxia whilst also avoiding chronic enhancement of
      tumour formation. We show that under likely physiological conditions neuroglobin
      can take part in a futile redox cycle. Determination of the rate constants for
      each of the steps in the cycle allows us to mathematically model the steady state
      concentration of the active anti-apoptotic ferrous form of neuroglobin under
      various conditions. Under likely normal physiological conditions neuroglobin is
      shown to be present in the ferrous state at approximately 30% of its total
      cellular concentration. Under hypoxic conditions this rapidly rises to
      approximately 80%. Temporal analysis of this model indicates that the transition
      from low concentrations to high concentration of ferrous neuroglobin occurs on
      the seconds time scale. These findings indicate a potential control model for the
      anti-apoptotic activity of neuroglobin, under likely physiological conditions,
      whereby, in normoxic conditions, the anti-apoptotic activity of neuroglobin is
      maintained at a low level, whilst immediately a transition occurs to a hypoxic
      situation, as might arise during stroke, the anti-apoptotic activity is
      drastically increased. In this way the cell avoids unwanted increased oncogenic
      potential under normal conditions, but the rapid activation of neuroglobin
      provides anti-apoptotic protection in times of acute hypoxia. 

PMID- 26305250
TI  - A Simulation Study of Categorizing Continuous Exposure Variables Measured with
      Error in Autism Research: Small Changes with Large Effects.
AB  - Variation in the odds ratio (OR) resulting from selection of cutoffs for
      categorizing continuous variables is rarely discussed. We present results for the
      effect of varying cutoffs used to categorize a mismeasured exposure in a
      simulated population in the context of autism spectrum disorders research.
      Simulated cohorts were created with three distinct exposure-outcome curves and
      three measurement error variances for the exposure. ORs were calculated using
      logistic regression for 61 cutoffs (mean +/- 3 standard deviations) used to
      dichotomize the observed exposure. ORs were calculated for five categories with a
      wide range for the cutoffs. For each scenario and cutoff, the OR, sensitivity,
      and specificity were calculated. The three exposure-outcome relationships had
      distinctly shaped OR (versus cutoff) curves, but increasing measurement error
      obscured the shape. At extreme cutoffs, there was non-monotonic oscillation in
      the ORs that cannot be attributed to "small numbers." Exposure misclassification
      following categorization of the mismeasured exposure was differential, as
      predicted by theory. Sensitivity was higher among cases and specificity among
      controls. Cutoffs chosen for categorizing continuous variables can have profound
      effects on study results. When measurement error is not too great, the shape of
      the OR curve may provide insight into the true shape of the exposure-disease
      relationship. 

PMID- 26305251
TI  - New Structure Sheds Light on Selective HIV-1 Genomic RNA Packaging.
AB  - Two copies of unspliced human immunodeficiency virus (HIV)-1 genomic RNA (gRNA)
      are preferentially selected for packaging by the group-specific antigen (Gag)
      polyprotein into progeny virions as a dimer during the late stages of the viral
      lifecycle. Elucidating the RNA features responsible for selective recognition of
      the full-length gRNA in the presence of an abundance of other cellular RNAs and
      spliced viral RNAs remains an area of intense research. The recent nuclear
      magnetic resonance (NMR) structure by Keane et al. [1] expands upon previous
      efforts to determine the conformation of the HIV-1 RNA packaging signal. The data
      support a secondary structure wherein sequences that constitute the major splice
      donor site are sequestered through base pairing, and a tertiary structure that
      adopts a tandem 3-way junction motif that exposes the dimerization initiation
      site and unpaired guanosines for specific recognition by Gag. While it remains to
      be established whether this structure is conserved in the context of larger RNA
      constructs or in the dimer, this study serves as the basis for characterizing
      large RNA structures using novel NMR techniques, and as a major advance toward
      understanding how the HIV-1 gRNA is selectively packaged. 

PMID- 26305252
TI  - Bio-Control of Salmonella Enteritidis in Foods Using Bacteriophages.
AB  - Two lytic phages, vB_SenM-PA13076 (PA13076) and vB_SenM-PC2184 (PC2184), were
      isolated from chicken sewage and characterized with host strains Salmonella
      Enteritidis (SE) ATCC13076 and CVCC2184, respectively. Transmission electron
      microscopy revealed that they belonged to the family Myoviridae. The lytic
      abilities of these two phages in liquid culture showed 104 multiplicity of
      infection (MOI) was the best in inhibiting bacteria, with PC2184 exhibiting more
      activity than PA13076. The two phages exhibited broad host range within the genus
      Salmonella. Phage PA13076 and PC2184 had a lytic effect on 222 (71.4%) and 298
      (95.8%) of the 311 epidemic Salmonella isolates, respectively. We tested the
      effectiveness of phage PA13076 and PC2184 as well as a cocktail combination of
      both in three different foods (chicken breast, pasteurized whole milk and Chinese
      cabbage) contaminated with SE. Samples were spiked with 1 * 10(4) CFU individual
      SE or a mixture of strains (ATCC13076 and CVCC2184), then treated with 1 * 10(8)
      PFU individual phage or a two phage cocktail, and incubated at 4  degrees C or 25
      degrees C for 5 h. In general, the inhibitory effect of phage and phage cocktail
      was better at 4  degrees C than that at 25  degrees C, whereas the opposite
      result was observed in Chinese cabbage, and phage cocktail was better than either
      single phage. A significant reduction in bacterial numbers (1.5-4 log CFU/sample,
      p < 0.05) was observed in all tested foods. The two phages on the three food
      samples were relatively stable, especially at 4 oC, with the phages exhibiting
      the greatest stability in milk. Our research shows that our phages have potential
      effectiveness as a bio-control agent of Salmonella in foods. 

PMID- 26305253
TI  - Dietary Patterns and Risk of Frailty in Chinese Community-Dwelling Older People
      in Hong Kong: A Prospective Cohort Study.
AB  - Dietary pattern analysis is an emerging approach to investigate the association
      between diet and frailty. This study examined the association of dietary patterns
      with frailty in 2724 Chinese community-dwelling men and women aged > 65 years.
      Baseline dietary data were collected using a food frequency questionnaire between
      2001 and 2003. Adherence to a priori dietary patterns, including the Diet Quality
      Index-International (DQI-I) and the Mediterranean Diet Score (MDS) was assessed.
      Factor analysis identified three a posteriori dietary patterns, namely
      "vegetables-fruits", "snacks-drinks-milk products", and "meat-fish". Incident
      frailty was defined using the FRAIL scale. Binary logistic regression was applied
      to examine the associations between dietary patterns and four-year incident
      frailty. There were 31 (1.1%) incident frailty cases at four years. Every 10-unit
      increase in DQI-I was associated with 41% reduced risk of frailty in the sex- and
      age-adjusted model (odds ratio (OR) (95% confidence interval (CI)): 0.59 (0.42
      0.85), p = 0.004). The association attenuated in the multivariate adjusted model
      (0.69 (0.47-1.02), p = 0.056). No association between other dietary patterns and
      incident frailty was observed. Our study showed that a better diet quality as
      characterized by higher DQI-I was associated with lower odds of developing
      frailty. The contribution of MDS or a posteriori dietary patterns to the
      development of frailty in Chinese older people remains to be explored. 

PMID- 26305254
TI  - Apple Polyphenols Decrease Atherosclerosis and Hepatic Steatosis in ApoE-/- Mice
      through the ROS/MAPK/NF-kappaB Pathway.
AB  - In this study, we examined the effects of apple polyphenols (APs) on
      hyperlipidemia, atherosclerosis, hepatic steatosis and endothelial function and
      investigated the potential mechanisms. ApoE(-/-) mice were fed a western-type
      diet and orally treated with APs (100 mg/kg) or atorvastatin (10 mg/kg) for 12
      weeks. Hyperlipidemia and atherosclerosis in the aortic sinuses and, and hepatic
      lipidosis were measured. The treatment with APs or atorvastatin induced a
      remarkable reduction in the atherosclerotic lesions and hepatic steatosis and
      decreased the levels of low-density lipoprotein, triglyceride, CCL-2 and VCAM-1
      levels in the plasma. Conversely, the APs significantly increased the plasma
      levels of high-density lipoprotein (HDL) cholesterol and markedly up-regulated
      the glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD)
      levels in liver tissues. Moreover, the APs treatment modulated lipid metabolism
      by up-regulating the transcription of associated hepatic genes including
      PPARalpha, while down-regulating the transcription of SCAP and its downstream
      genes associated with lipid synthesis in the liver. Histological assessment
      showed that the APs treatment also reduced the macrophage infiltration in the
      aortic root plaque and the inflammatory cells infiltrations to the liver tissues.
      Moreover, we confirmed that the APs treatment greatly reduced the ox-LDL-induced
      endothelial dysfunction and monocyte adhesion to rat aortic endothelial cells
      (RAECs). Mechanistically, the APs treatment suppressed the ROS/MAPK/NF-kappaB
      signaling pathway, and consequently, reduced CCL-2, ICAM-1 and VCAM-1 expression.
      Our results suggest that the APs are a beneficial nutritional supplement for the
      attenuation of atherosclerosis. 

PMID- 26305255
TI  - Objective Understanding of Front-of-Package Nutrition Labels among Nutritionally
      At-Risk Individuals.
AB  - In the ongoing debate about front-of-package (FOP) nutrition labels, little data
      exist regarding nutritionally at-risk populations, although they are critical
      targets of prevention programs. This study aimed to compare the impact of FOP
      labels on the ability to rank products according to their nutritional quality
      among French adults potentially at risk of poor dietary quality (N = 14,230).
      Four labels were evaluated: Guideline Daily Amounts (GDA), Multiple Traffic
      Lights (MTL), 5-Color Nutrition Label (5-CNL), Green Tick (Tick), along with a
      reference without label. Mixed models were used to assess how individual
      characteristics and FOP labels were associated with the ability to rank products.
      Older participants and those with a lower educational level, income, nutritional
      knowledge, and likelihood of reading nutrition facts were less skilled at ranking
      food products according to nutritional quality. Compared with individual
      characteristics, nutrition labels had an increased impact on food product ranking
      ability. Overall, 5-CNL corresponded to the highest rate of correct responses,
      followed by MTL, GDA, and Tick (p < 0.0001). The strongest impact of 5-CNL was
      observed among individuals with no nutritional knowledge (odds ratio (OR): 20.24;
      95% confidence interval (CI): 13.19-31.06). Therefore, 5-CNL appeared to be
      effective at informing consumers, including those who are nutritionally at-risk,
      about the nutritional quality of food products. 

PMID- 26305256
TI  - Triggering of Erythrocyte Death by Triparanol.
AB  - The cholesterol synthesis inhibitor Triparanol has been shown to trigger
      apoptosis in several malignancies. Similar to the apoptosis of nucleated cells,
      erythrocytes may enter eryptosis, the suicidal death characterized by cell
      shrinkage and cell membrane scrambling with phosphatidylserine translocation to
      the erythrocyte surface. Triggers of eryptosis include oxidative stress which may
      activate erythrocytic Ca(2+) permeable unselective cation channels with
      subsequent Ca(2+) entry and increase of cytosolic Ca(2+) activity ([Ca(2+)]i).
      The present study explored whether and how Triparanol induces eryptosis. To this
      end, phosphatidylserine exposure at the cell surface was estimated from annexin-V
      binding, cell volume from forward scatter, hemolysis from hemoglobin release,
      [Ca(2+)]i from Fluo3-fluorescence, and ROS formation from 2',7'
      dichlorodihydrofluorescein diacetate (DCFDA) dependent fluorescence. As a result,
      a 48 h exposure of human erythrocytes to Triparanol (20 uM) significantly
      increased DCFDA fluorescence and significantly increased Fluo3-fluorescence.
      Triparanol (15 uM) significantly increased the percentage of annexin-V-binding
      cells, and significantly decreased the forward scatter. The effect of Triparanol
      on annexin-V-binding was significantly blunted, but not abolished by removal of
      extracellular Ca(2+). In conclusion, Triparanol leads to eryptosis, the suicidal
      erythrocyte death characterized by cell shrinkage and phospholipid scrambling of
      the erythrocyte cell membrane. Triparanol is at least in part effective by
      stimulating ROS formation and Ca(2+) entry. 

PMID- 26305258
TI  - Markov Chain-Like Quantum Biological Modeling of Mutations, Aging, and Evolution.
AB  - Recent evidence suggests that quantum mechanics is relevant in photosynthesis,
      magnetoreception, enzymatic catalytic reactions, olfactory reception,
      photoreception, genetics, electron-transfer in proteins, and evolution; to
      mention few. In our recent paper published in Life, we have derived the operator
      sum representation of a biological channel based on codon basekets, and
      determined the quantum channel model suitable for study of the quantum biological
      channel capacity. However, this model is essentially memoryless and it is not
      able to properly model the propagation of mutation errors in time, the process of
      aging, and evolution of genetic information through generations. To solve for
      these problems, we propose novel quantum mechanical models to accurately describe
      the process of creation spontaneous, induced, and adaptive mutations and their
      propagation in time. Different biological channel models with memory, proposed in
      this paper, include: (i) Markovian classical model, (ii) Markovian-like quantum
      model, and (iii) hybrid quantum-classical model. We then apply these models in a
      study of aging and evolution of quantum biological channel capacity through
      generations. We also discuss key differences of these models with respect to a
      multilevel symmetric channel-based Markovian model and a Kimura model-based
      Markovian process. These models are quite general and applicable to many open
      problems in biology, not only biological channel capacity, which is the main
      focus of the paper. We will show that the famous quantum Master equation
      approach, commonly used to describe different biological processes, is just the
      first-order approximation of the proposed quantum Markov chain-like model, when
      the observation interval tends to zero. One of the important implications of this
      model is that the aging phenotype becomes determined by different underlying
      transition probabilities in both programmed and random (damage) Markov chain-like
      models of aging, which are mutually coupled. 

PMID- 26305257
TI  - MicroRNAs and Chinese Medicinal Herbs: New Possibilities in Cancer Therapy.
AB  - In recent decades Chinese medicine has been used worldwide as a complementary and
      alternative medicine to treat cancer. Plenty of studies have shown that microRNAs
      (miRNAs) play fundamental roles in many pathological processes, including cancer,
      while the anti-cancer mechanisms of Chinese medicinal herbs targeting miRNAs also
      have been extensively explored. Our previous studies and those of others on
      Chinese medicinal herbs and miRNAs in various cancer models have provided a
      possibility of new cancer therapies, for example, up-regulating the expression of
      miR-23a may activate the positive regulatory network of p53 and miR-23a involved
      in the mechanism underlying the anti-tumor effect of berberine in hepatocellular
      carcinoma (HCC). In this review, we survey the role of Chinese medicinal herbal
      products in regulating miRNAs in cancer and the use of mediating miRNAs for
      cancer treatment. In addition, the controversial roles of herb-derived exogenous
      miRNAs in cancer treatment are also discussed. It is expected that targeting
      miRNAs would provide a novel therapeutic approach in cancer therapy by improving
      overall response and survival outcomes in cancer treatment, especially when
      combined with conventional therapeutics and Chinese medicinal herbal products. 

PMID- 26305259
TI  - Social/Electronic Media Use of Children and Adolescents Who Attend the Pediatric
      Weight Management Programs of the COMPASS Network.
AB  - BACKGROUND: Obesity is a major healthcare problem in youth and their
      social/electronic media (SEM) use has been described as a risk factor. Though
      much is known about the newer technologies youth use to communicate, little is
      known about what is used by those in weight management programs. The aim of this
      study was to determine what types of SEM, including sedentary and active video
      games, youth in weight management programs use and which they prefer for
      communicating with healthcare providers. METHODS/DESIGN: This was a multisite
      study using a 24-question online SurveyMonkey(r) questionnaire. Youth, 12-17
      years old, attending pediatric weight management programs at seven participating
      centers in the Childhood Obesity Multi Program Analysis and Study System network
      were eligible. RESULTS: There were 292 responders with a mean age of 14.2 years.
      Fifty-four percent were female, 36% Caucasian, 35% African American, and 33% were
      Hispanic. Ninety-four percent had access to a computer, 71% had Internet access,
      and 63% had smartphones. Whereas 87% had at least one gaming system at home, 50%
      reported they never played sedentary video games (71% of females vs. 25% males; p
      < 0.0001) and 63% never played exercise video games during the week. The
      preferred method of communication with a healthcare provider was face to face
      (60%), with few indicating a preference for communication by texting (13%), phone
      (12%), or social media (6%). CONCLUSIONS: Face-to-face communication with
      healthcare providers is the preferred method for youth in pediatric weight
      management programs. They self-reported video game use less than previously
      described.

PMID- 26305260
TI  - Cellulose Derived Graphenic Fibers for Capacitive Desalination of Brackish Water.
AB  - We describe a simple and inexpensive cellulose-derived and layer-by-layer stacked
      carbon fiber network electrode for capacitive deionization (CDI) of brackish
      water. The microstructure and chemical composition were characterized using
      spectroscopic and microscopic techniques; electrochemical/electrical performance
      was evaluated by cyclic voltammetry and 4-probe electrical conductivity and
      surface area by Brunauer-Emmett-Teller analysis, respectively. The desalination
      performance was investigated using a laboratory batch model CDI unit, under fixed
      applied voltage and varying salt concentrations. Electro-adsorption of NaCl on
      the graphite reinforced-cellulose (GrC) electrode reached equilibrium quickly
      (within 90 min) and the adsorbed salts were released swiftly (in 40 min) back
      into the solution, during reversal of applied potential. X-ray photoelectron
      spectroscopic studies clearly illustrate that sodium and chloride ions were
      physisorbed on the negative and positive electrodes, respectively during electro
      adsorption. This GrC electrode showed an electro-adsorption capacity of 13.1 mg/g
      of the electrode at a cell potential of 1.2 V, with excellent recyclability and
      complete regeneration. The electrode has a high tendency for removal of specific
      anions, such as fluoride, nitrate, chloride, and sulfate from water in the
      following order: Cl->NO3->F->SO4(2-). GrC electrodes also showed resistance to
      biofouling with negligible biofilm formation even after 5 days of incubation in
      Pseudomonas putida bacterial culture. Our unique cost-effective methodology of
      layer-by-layer stacking of carbon nanofibers and concurrent reinforcement using
      graphite provides uniform conductivity throughout the electrode with fast electro
      adsorption, rapid desorption, and extended reuse, making the electrode affordable
      for capacitive desalination of brackish water.

PMID- 26305262
TI  - Negative linear compressibility in a crystal of alpha-BiB3O6.
AB  - Negative linear compressibility (NLC), a rare and important mechanical effect
      with many application potentials, in a crystal of alpha-BiB3O6 (BIBO) is
      comprehensively investigated using first-principles calculations and high
      pressure synchrotron X-ray diffraction experiments. The results indicate that the
      BIBO crystal exhibits the second largest NLC among all known inorganic materials
      over a broad pressure range. This unusual NLC behaviour is due to the rotation
      and displacement of the rigid [BO3] and [BO4] building units that result in hinge
      motion in an umbrella-like topology. More importantly, the parallel-polar lone
      pair electrons on the Bi(3+) cations act as "umbrella stands" to withstand the B
      O hinges, thus significantly enhancing the NLC effect. BIBO presents a unique
      example of a "collapsible umbrella" mechanism for achieving NLC, which could be
      applied to other framework materials with lone-pair electrons. 

PMID- 26305261
TI  - Plant sulfur nutrition: From Sachs to Big Data.
AB  - Together with water and carbon dioxide plants require 14 essential mineral
      nutrients to finish their life cycle. The research in plant nutrition can be
      traced back to Julius Sachs, who was the first to experimentally prove the
      essentiality of mineral nutrients for plants. Among those elements Sachs showed
      to be essential is sulfur. Plant sulfur nutrition has been not as extensively
      studied as the nutrition of nitrogen and phosphate, probably because sulfur was
      not limiting for agriculture. However, with the reduction of atmospheric sulfur
      dioxide emissions sulfur deficiency has become common. The research in sulfur
      nutrition has changed over the years from using yeast and algae as experimental
      material to adopting Arabidopsis as the plant model as well as from simple
      biochemical measurements of individual parameters to system biology. Here the
      evolution of sulfur research from the times of Sachs to the current Big Data is
      outlined. 

PMID- 26305263
TI  - Synthesis and Characterization of a Bronsted Pair Functionalized Shape-Persistent
      Macrocycle.
AB  - The first shape-persistent macrocycle 1 offering a Bronsted pair functionalized
      interior is described. Via postcyclization transformation, this heterosequenced
      compound can be obtained from its corresponding ester 2. The macrocycles differ
      dramatically in their characteristics such as solubility and appearance.
      Theoretical investigations suggest that those contrasts might originate from
      conformational changes due to the formation of a strong O-H-N hydrogen bond in 1.

PMID- 26305264
TI  - Arbuscular mycorrhizal symbiosis induces strigolactone biosynthesis under drought
      and improves drought tolerance in lettuce and tomato.
AB  - Arbuscular mycorrhizal (AM) symbiosis alleviates drought stress in plants.
      However, the intimate mechanisms involved, as well as its effect on the
      production of signalling molecules associated with the host plant-AM fungus
      interaction remains largely unknown. In the present work, the effects of drought
      on lettuce and tomato plant performance and hormone levels were investigated in
      non-AM and AM plants. Three different water regimes were applied, and their
      effects were analysed over time. AM plants showed an improved growth rate and
      efficiency of photosystem II than non-AM plants under drought from very early
      stages of plant colonization. The levels of the phytohormone abscisic acid, as
      well as the expression of the corresponding marker genes, were influenced by
      drought stress in non-AM and AM plants. The levels of strigolactones and the
      expression of corresponding marker genes were affected by both AM symbiosis and
      drought. The results suggest that AM symbiosis alleviates drought stress by
      altering the hormonal profiles and affecting plant physiology in the host plant.
      In addition, a correlation between AM root colonization, strigolactone levels and
      drought severity is shown, suggesting that under these unfavourable conditions,
      plants might increase strigolactone production in order to promote symbiosis
      establishment to cope with the stress. 

PMID- 26305265
TI  - What does Piraha grammar have to teach us about human language and the mind?
AB  - Piraha is a language isolate of the Brazilian Amazon. Among the lessons it has to
      teach us about human language and the mind, two are highlighted here. The first
      is that recursion is not a necessary condition for human syntax, because there is
      no evidence for recursive sentential syntax in the language. This is a stark
      counterexample to the claims of Chomsky and others. The second lesson is that the
      influence of culture on Piraha grammar, coupled with much established and newer
      research, indicates that the idea of an innate, universal grammar has little if
      any role to play in our understanding of the nature, origins, and use of human
      language. WIREs Cogn Sci 2012 doi: 10.1002/wcs.1195 For further resources related
      to this article, please visit the WIREs website. 

PMID- 26305266
TI  - Psychology of spatial cognition.
AB  - In this overview, focusing on memory and higher cognitive processes, we cover
      some of the most relevant results that emerged from research on spatial cognition
      in animals and in humans in the last 3 decades. In particular, we discuss how
      representations of distance and direction are used to localize oneself with
      respect to the external world, to determine the position of objects with respect
      to each other, and to compute the position of invisible goals. The role of
      landmarks and environmental geometry as cues for extracting spatial information
      in such abilities is compared, and the reliance upon self-centered and external
      frames of reference is discussed. Moreover, the contribution of working memory
      and processing strategies in forming representations of spatial relations in
      humans is presented. Finally, implications for some neighboring fields of the
      cognitive sciences will be outlined. WIREs Cogn Sci 2012. doi: 10.1002/wcs.1198
      For further resources related to this article, please visit the WIREs website. 

PMID- 26305267
TI  - Social learning and traditions in animals: evidence, definitions, and
      relationship to human culture.
AB  - The number of publications concerned with social learning in nonhuman animals has
      expanded dramatically in recent decades. In this article, recent literature
      addressing three issues that have been of particular concern to those with both
      an interest in social learning and a background in experimental psychology are
      reviewed: (1) the definition as well as (2) empirical investigation of the
      numerous behavioral processes that support social learning in animals, and (3)
      the relationship of the 'traditions' seen in animals to the 'culture' that is so
      important in shaping the development of behavioral repertoires in humans. WIREs
      Cogn Sci 2012 doi: 10.1002/wcs.1196 For further resources related to this
      article, please visit the WIREs website. 

PMID- 26305268
TI  - Dynamics of cognition.
AB  - The application of dynamical systems methods and concepts to cognitive phenomena
      has broadened the range of testable hypotheses and theoretical narratives
      available to cognitive scientists. Most research in cognitive dynamics tests the
      degree to which observed cognitive performance is consistent with one or another
      core phenomena associated with complex dynamical systems, such as tests for phase
      transitions, coupling among processes, or scaling laws. Early applications of
      dynamical systems theory to perceptual-motor performance and developmental
      psychology paved the way for more recent applications of dynamical systems
      analyses, models, and theoretical concepts in areas such as learning, memory,
      speech perception, decision making, problem solving, and reading, among others.
      Reviews of the empirical results of both foundational and contemporary cognitive
      dynamics are provided. WIREs Cogn Sci 2012. doi: 10.1002/wcs.1200 For further
      resources related to this article, please visit the WIREs website. 

PMID- 26305269
TI  - Blindsight: recent and historical controversies on the blindness of blindsight.
AB  - The phenomenon 'blindsight' has received much interest from neuroscientists,
      philosophers, and psychologists during the last decades. Several researchers seem
      to agree that blindsight might be of great importance in the ambition to find
      neural correlates of consciousness. However, the history of blindsight is a
      history of changing experimental paradigms and very few patients. In late 19th
      century, researchers debated why lesions to primary visual cortex seemingly left
      some visual abilities intact in animals, while human patients reported to be
      blind. From the 1970s until today, experiments have attempted to compare measures
      of conscious and unconscious perception, suggesting a distinction between visual
      functions and visual experience. However, more recently, newer methods and an
      interest in introspective reports have cast doubts about the 'blindness' of
      blindsight. A cautious conclusion is suggested, though current research can be
      interpreted in different ways. WIREs Cogn Sci 2012 doi: 10.1002/wcs.1194 For
      further resources related to this article, please visit the WIREs website. 

PMID- 26305270
TI  - The role of guidance in children's discovery learning.
AB  - Discovery learning is an important, yet controversial topic in the fields of
      psychology, education, and cognitive science. Though traditional views emphasize
      a lack of instructional constraint or scaffolding, more recent evidence suggests
      that guidance should be included in the process of discovery learning. The
      present review summarizes three general approaches which have been shown to
      facilitate guided discovery learning: (1) strategic presentation of materials,
      (2) consequential feedback, and (3) probing questions and self-explanations.
      Techniques for implementing approaches are discussed, as well as the underlying
      mechanisms that contribute to their effectiveness. WIREs Cogn Sci 2012. doi:
      10.1002/wcs.1199 For further resources related to this article, please visit the
      WIREs website. 

PMID- 26305271
TI  - Conductive elastomers with autonomic self-healing properties.
AB  - Healable, electrically conductive materials are highly desirable and valuable for
      the development of various modern electronics. But the preparation of a material
      combining good mechanical elasticity, functional properties, and intrinsic self
      healing ability remains a great challenge. Here, we design composites by
      connecting a polymer network and single-walled carbon nanotubes (SWCNTs) through
      host-guest interactions. The resulting materials show bulk electrical
      conductivity, proximity sensitivity, humidity sensitivity and are able to self
      heal without external stimulus under ambient conditions rapidly. Furthermore,
      they also possess elasticity comparable to commercial rubbers. 

PMID- 26305272
TI  - High Performance Full Sodium-Ion Cell Based on a Nanostructured Transition Metal
      Oxide as Negative Electrode.
AB  - A novel design of a sodium-ion cell is proposed based on the use of
      nanocrystalline thin films composed of transition metal oxides. X-ray
      diffraction, Raman spectroscopy and electron microscopy were helpful techniques
      to unveil the microstructural properties of the pristine nanostructured
      electrodes. Thus, Raman spectroscopy revealed the presence of amorphous NiO,
      alpha-Fe2 O3 (hematite) and gamma-Fe2 O3 (maghemite). Also, this technique
      allowed the calculation of an average particle size of 23.4 A in the amorphous
      carbon phase in situ generated on the positive electrode. The full sodium-ion
      cell performed with a reversible capacity of 100 mA h g(-1) at C/2 with an output
      voltage of about 1.8 V, corresponding to a specific energy density of about 180 W
      h kg(-1) . These promising electrochemical performances allow these transition
      metal thin films obtained by electrochemical deposition to be envisaged as
      serious competitors for future negative electrodes in sodium-ion batteries.

PMID- 26305273
TI  - Spray Freeze-Drying as an Alternative to the Ionic Gelation Method to Produce
      Chitosan and Alginate Nano-Particles Targeted to the Colon.
AB  - Chitosan and alginate nano-composite (NP) carriers intended for colonic delivery
      containing prednisolone and inulin were obtained by two processes. Spray freeze
      drying using chitosan (SFDC) or alginate (SFDA) was proposed as an alternative to
      the traditional chitosan-tripolyphosphate platform (CTPP). NPs were fully
      characterised and assessed for their yield of particles; level of prednisolone
      and inulin release in phosphate and Krebs buffers; and sensitivity to degradation
      by lysozyme, bacteria and faecal slurry. NPs based on chitosan showed similar
      properties (size, structure, viscoelastic behaviour), but those based on SFDC
      showed a higher mean release of both active ingredients, with similar efficiency
      of encapsulation and loading capacity for prednisolone but lower for inulin. SFDC
      was less degraded in the presence of lysozyme and E. coli and was degraded by B.
      thetaiotaomicron but not by faecal slurry. The results obtained with SFDA were
      promising because this NP showed good encapsulation parameters for both active
      ingredients and biological degradability by E. coli and faecal slurry. However,
      it will be necessary to use alginate derivatives to reduce its solubility and
      improve its mechanical behaviour.

PMID- 26305274
TI  - Valproic Acid Induces the Hyperacetylation of P53, Expression of P53 Target
      Genes, and Markers of the Intrinsic Apoptotic Pathway in Midorganogenesis Murine
      Limbs.
AB  - In utero exposure to valproic acid (VPA), an anticonvulsant and histone
      deacetylase inhibitor (HDACi), increases the risk of congenital malformations.
      Although the mechanisms leading to the teratogenicity of VPA remain unsolved,
      several HDAC inhibitors increase cell death in cancer cell lines and embryonic
      tissues. Moreover, P53, the master regulator of apoptosis, is an established HDAC
      target. The purpose of this study was to investigate the effects of VPA on P53
      signaling and markers of apoptosis during midorganogenesis in vitro limb
      development. Timed-pregnant CD1 mice (gestation day 12) were euthanized;
      embryonic forelimbs were excised and cultured in vitro for 3, 6, 12, or 24 hr in
      the presence or absence of VPA or valpromide (VPD), a non-HDACi analog of VPA.
      Quantitative RT-PCR and Western blots were used to assess the expression of
      candidate genes and proteins involved in P53 signaling and apoptosis. P53
      hyperacetylation and a decrease (Survivin/Birc5 and Bcl2) or an increase
      (p21/Cdkn1a) in the expression of p53 target genes was observed only in VPA
      exposed limbs. VPA exposure also triggered an increase in markers of apoptosis
      and DNA damage; the concentrations of cleaved caspase 9 and caspase 3, cleaved
      poly (ADP-ribose) polymerase, and gamma-H2AX were increased in VPA-exposed limbs.
      VPD treatment caused a small but significant increase in cleaved caspase 3. Thus,
      in vitro exposure to an HDACi such as VPA leads to P53 hyperacetylation, enhances
      the expression of P53 target genes, and triggers an increase in apoptosis that
      may contribute to teratogenicity. 

PMID- 26305275
TI  - Enhancing the Thermal Stability of Solution-Processed Small-Molecule
      Semiconductor Thin Films Using a Flexible Linker Approach.
AB  - Using flexible aliphatic chains to link conjugated molecular semiconductors
      affords a polymeric material that possesses defined conjugated segments but
      extended covalent connectivity, which enhances crystallinity and thermal
      stability in field-effect transistors and bulk heterojunction solar-cell devices
      when used as an additive. 

PMID- 26305276
TI  - Risk factors for recurrence after surgery in non-metastatic RCC with thrombus: a
      contemporary multicentre analysis.
AB  - OBJECTIVE: To determine the predictors of post-surgical recurrence for patients
      with non-metastatic renal cell carcinoma (RCC) and venous thrombus. METHODS:
      Records from consecutive patients with non-metastatic RCC with tumour thrombus,
      treated surgically between 2000 and 2012 at one of three centres, were reviewed.
      Univariable and multivariable analysis were used to evaluate the association of
      risk factors for post-surgical recurrence. RESULTS: A total of 465 patients with
      non-metastatic RCC were identified, including patients with thrombus present in
      the renal vein (257 patients, 55.3%), infrahepatic inferior vena cava (IVC; 144
      patients, 31.0%) and suprahepatic IVC (64 patients, 13.8%). The median
      (interquartile range) follow-up was 28.3 (12.2-56.4) months, with metastatic RCC
      developing in 188 patients (40.5%). Independent predictors of recurrence
      included: body mass index <=20 kg/m(2) (hazard ratio [HR] 2.66; 95% confidence
      interval [CI] 1.29-5.49), low preoperative haemoglobin (HR 1.54; 95% CI 1.07
      2.20), perinephric fat invasion (HR 1.51; 95% CI 1.09-2.10), IVC thrombus height
      (HR 2.64; 95% CI 1.47-4.74), tumour diameter (HR 1.04 95% CI 1.00-1.09), nuclear
      grade (HR 1.56 95% CI 1.12-2.15) and non-clear-cell histology (HR 2.13; 95% CI
      1.30-3.50). Independently predictive variables were used to create a recurrence
      model for three risk groups based on 0, 1-2, or >2 risk factors, respectively.
      The 5-year recurrence-free survival rate was significantly different in patients
      with favourable-risk (79.1%) compared with intermediate- (55.1%) or high-risk
      (22.1%) disease (P < 0.001). CONCLUSIONS: Seven risk factors for recurrence were
      identified for patients with non-metastatic RCC with thrombus, which can be used
      to select patients who may benefit from increased surveillance or adjuvant
      therapy clinical trials.

PMID- 26305277
TI  - An integrated curriculum approach to increasing habitual physical activity in
      deprived South Asian children.
AB  - Integrating physical activity (PA) within a school curriculum is a promising
      approach for increasing PA in children. To date, no research has examined its
      effectiveness in increasing the low levels of PA witnessed in deprived South
      Asian (SA) children. The study aims to ascertain whether an integrated school
      based curriculum and pedometer intervention could increase PA in children from
      deprived SA backgrounds. Following ethical approval and informed consent, 134
      deprived SA children (63 boys, 71 girls, control (n = 40, mean age = 11.12 years,
      SD = 0.32 years) and intervention (n = 94, mean age = 9.48 years, SD = 0.62
      years)) from a primary school in England, UK, completed a 6-week integrated PA
      intervention based on virtually walking from their school (middle of the country)
      to the coast and back (March-July 2013). Habitual PA was determined at baseline
      and post 6 weeks intervention for both groups, and determined weekly during the
      intervention in the experimental group. The results indicated that average daily
      steps were significantly higher at post 6 weeks compared to baseline for the
      intervention group (intervention mean change = 8694 steps/day, SD = 7428
      steps/day vs. control mean change = -1121 steps/day, SD = 5592 steps/day, 95% CI
      of difference, 6726-7428 steps/day, P = .001, d = 1.76). In addition, significant
      decreases in BF% and waist circumference were observed in the intervention group
      post 6 weeks (mean change for BF% = -4.5%, mean change for WC = -1.7 cm, P =
      .001). School-based integrated curriculum and pedometer interventions provide a
      feasible and effective mechanism for increasing habitual PA in primary school
      children from deprived SA backgrounds.

PMID- 26305278
TI  - Synergistic effects of gene polymorphisms of the renin-angiotensin-aldosterone
      system on essential hypertension in Kazakhs in Xinjiang.
AB  - OBJECTIVE: To assess the synergistic effects of gene polymorphisms of the renin
      angiotensin-aldosterone system (RAAS) on essential hypertension (EH) in Kazakhs
      in Xinjiang. METHODS: A cross-sectional case-control association study was
      conducted in 52 1 hypertensive and 623 normotensive subjects of Kazakh ethnicity
      on eight common single nucleotide polymorphisms (SNPs) interspersed over five
      genes of the RAAS. SNPs were genotyped by polymerase chain reaction-restriction
      fragment length polymorphism. Interactions among the SNPs were analyzed by the
      multifactor dimensionality reduction method (MDR). RESULTS: In single-locus
      analysis, subjects with AGT -6G, ACE D, and CYP11B2 -344C had increased
      susceptibility to EH (OR: 1.249; 1.425; 1.201). When subgrouped by sex, males
      with the t allele of REN Taq I had decreased risk for EH (OR: 0.529), and those
      with AGT -6G and CYP11B2 -344 C had increased risk for EH (OR: 1.498; 1.449). In
      females, carrying ACE D increased the risk for EH. (OR: 1.327). In six AGT
      haplotypes, H1 was protective, while H3 increased susceptibility to EH (OR:
      0.683; 2.025). Interaction analysis by MDR showed that there was a strong
      synergistic effect between ACE I/D and CY11B2 (T-344C) and a moderate interaction
      between both ACE I/D and CY11B2 T-344C and AGT A-6G. CONCLUSIONS: There was a
      strong synergistic effect between ACE I/D and CY11B2 T-344C and a moderate effect
      between both ACE I/D and CY11B2 T-344C and AGT A-6G. AGT -6G, ACE D, and CY11B2 
      344C increased susceptibility to EH. REN Taq I, AGT -6G, CY11B2 -344 C and ACE D
      were associated with male and female EH, respectively. H1 and H3 of AGT were
      protective and risk haplotypes, respectively.

PMID- 26305279
TI  - Biochemical Characterization of Dovyalis hebecarpa Fruits: A Source of
      Anthocyanins with High Antioxidant Capacity.
AB  - Dovyalis hebecarpa, which is also known as the Ceylon gooseberry, is an
      attractive exotic purple berry that is produced in the southwest of Brazil with
      high yields. Current literature lacks information about the nutritional
      composition and antioxidant capacity of this fruit. As such, this work aimed to
      evaluate and compare the proximate composition, phytochemical content, and
      antioxidant capacity of D. hebecarpa over two seasons through the application of
      a range of different methods, including FRAP, ABTS, and ORAC assays. The
      proximate composition and biometric parameters were monitored for quality
      purposes. The results significantly changed between seasons in accordance with
      variations in rain incidence and average temperatures. The Ceylon gooseberry
      contained a similar or higher content of anthocyanins (ACY) than other berries
      commonly consumed in human diet. These ACY were identified at higher levels in
      the fruit's skin (284 to 351 mg of cyanidin-3-glucoside equivalents/100 g of
      fresh weight [FW]) than in its pulp (49 to 69 mg/100 g of FW). The use of an ORAC
      assay identified higher antioxidant activity (145 MUmol of Trolox equivalents
      [TE]/g in the skins and 179 MUmol of TE/g in the pulp on a FW basis) than all
      other methods used to determine antioxidant activity. Thus, D. hebecarpa is a
      rich source of ACY that demonstrates high antioxidant activity against the
      peroxyl radicals formed in ORAC assay conditions. PRACTICAL APPLICATION: Ceylon
      gooseberry fruit is a source of phytochemicals that could be used in the human
      diet providing defense against free radicals damage. Moreover, the skins of the
      fruit, which are not typically consumed, contained higher levels of polyphenols
      than the pulp. This indicates that the skins of the Ceylon gooseberry may
      represent a promising source of natural pigments and antioxidants for industrial
      applications.

PMID- 26305280
TI  - Con: Corticosteroids Are Useful in the Management of HAPE.

PMID- 26305281
TI  - The VetDIT and Veterinary Ethics Education.

PMID- 26305282
TI  - The VetDIT and Veterinary Ethics Education.

PMID- 26305283
TI  - Styrene-associated health outcomes at a windblade manufacturing plant.
AB  - BACKGROUND: Health risks of using styrene to manufacture windblades for the green
      energy sector are unknown. METHODS: Using data collected from 355 (73%) current
      windblade workers and regression analysis, we investigated associations between
      health outcomes and styrene exposure estimates derived from urinary styrene
      metabolites. RESULTS: The median current styrene exposure was 53.6 mg/g
      creatinine (interquartile range: 19.5-94.4). Color blindness in men and women
      (standardized morbidity ratios 2.3 and 16.6, respectively) was not associated
      with exposure estimates, but was the type previously reported with styrene.
      Visual contrast sensitivity decreased and chest tightness increased (odds ratio
      2.9) with increasing current exposure. Decreases in spirometric parameters and
      FeNO, and increases in the odds of wheeze and asthma-like symptoms (odds ratios
      1.3 and 1.2, respectively) occurred with increasing cumulative exposure.
      CONCLUSIONS: Despite styrene exposures below the recommended 400 mg/g creatinine,
      visual and respiratory effects indicate the need for additional preventative
      measures in this industry.

PMID- 26305284
TI  - Biomechanical Properties of the Skin in Patients with Breast Cancer-Related
      Lymphedema Compared to Healthy Individuals.
AB  - BACKGROUND: Biomechanical skin changes in breast cancer-related lymphedema (BRCL)
      have barely been described and objectively tested. This study aims to compare the
      skin of upper limb lymphedema with skin of the healthy contralateral arm, in
      order to demonstrate changes of elasticity, viscoelasticity, and level of
      hydration of the skin in BCRL. The secondary aim is to investigate the
      correlation between biomechanical skin changes and measurements that are
      currently used in clinical practice, such as volume measurement and lymph-ICF
      score. METHODS AND RESULTS: Eighteen patients with BCRL and 18 healthy
      individuals were included in the study. A Cutometer(r) was used for measurements
      for skin elasticity and viscoelasticity on both arms of each subject. A
      Corneometer(r) was used for measurements of skin hydration. Measurements of both
      test groups were compared. In BCRL patients, there was a significant difference
      (p = < 0.028) between the elasticity of the skin of the lymphedema arm compared
      to the healthy contralateral arm. There were no significant differences for level
      of skin hydration or viscoelasticity in lymphedema patients between the
      measurements on the skin of the lymphedematous and healthy arm. In healthy
      individuals, there were no significant differences for all measurements between
      skin of both arms. Spearman's correlation was significant (p = < 0.01) for
      difference in volume and difference in elasticity in BCRL patients. CONCLUSION:
      This study shows an impaired elasticity for the skin of the lower arm in patients
      with lymphedema compared to the contralateral healthy arm. Promising evidence is
      suggested for the use of the Cutometer device in the diagnostic evaluation of
      BCRL.

PMID- 26305285
TI  - Personal views about womanhood amongst women living with HIV in Botswana.
AB  - The social construction of womanhood in Africa can be said to have two central
      defining elements: being a wife and being a mother. The interplay between HIV and
      these elements is not well understood outside of prevention efforts. We conducted
      a qualitative study of womanhood in Botswana; specifically the sexual and
      reproductive lives of women living with HIV. Twelve focus-group discussions were
      held with 61 women, with a median age of 35, taking anti-retroviral therapy.
      Major themes describing womanhood, before and after HIV diagnosis, were
      identified using grounded theory strategies. Findings illustrate that womanhood
      is synonymous with motherhood and that women are expected to have sex in order to
      please a partner. HIV was said to create a barrier to fulfilling these
      expectations as it caused anxiety over disclosing one's HIV status and/or
      infecting the partner. The sense of pride and dignity that traditionally
      accompanied pregnancy was said to be lost and a common refrain was concern about
      passing HIV to an unborn child, having pregnancy complications or advancing HIV
      infection. Fear, shame and stigma play a large role in these negative
      perceptions. Interventions to address stigma, societal views of women and the
      integration of holistic family planning into HIV care are needed. 

PMID- 26305288
TI  - Synthetic Small Molecules Derived from Natural Vitamin K Homologues that Induce
      Selective Neuronal Differentiation of Neuronal Progenitor Cells.
AB  - We synthesized new vitamin K2 analogues with omega-terminal modifications of the
      side chain and evaluated their selective differentiation of neuronal progenitor
      cells into neurons in vitro. The result of the assay showed that the menaquinone
      3 analogue modified with the m-methylphenyl group had the most potent activity,
      which was twice as great as the control. This finding indicated that it is
      possible to obtain much more potent compounds with modification of the structure
      of vitamin K2. 

PMID- 26305287
TI  - Long-term effects of early-life caregiving experiences on brain-derived
      neurotrophic factor histone acetylation in the adult rat mPFC.
AB  - Infant-caregiver experiences are major contributing factors to neural and
      behavioral development. Research indicates that epigenetic mechanisms provide a
      way in which infant-caregiver experiences affect gene activity and other
      downstream processes in the brain that influence behavioral development. Our
      laboratory previously demonstrated in a rodent model that exposure to
      maltreatment alters methylation of DNA associated with the brain-derived
      neurotrophic factor (bdnf) and reelin genes as well as mRNA of key epigenetic
      regulatory genes in the medial prefrontal cortex (mPFC). In the current study, we
      characterized patterns of histone acetylation at bdnf and reelin gene loci after
      our caregiver manipulations. Using a within-litter design (n = 8-10/group from
      eight litters), pups were exposed to adverse (maltreatment condition: exposure to
      a stressed caregiver) or nurturing (cross-foster condition: exposure to a
      nurturing caregiver) caregiving environments outside the home cage for 30 min
      daily during the first postnatal week. Remaining pups in a litter were left with
      the biological mother during each session (providing normal care controls). We
      then used chromatin immunoprecipitation (ChIP) and quantitative RT-PCR to measure
      histone 3 lysine 9/14 acetylation associated with bdnf promoters I and IV and the
      reelin promoter in the adult mPFC. Maltreated females had decreased acetylation
      at bdnf IV, while neither males nor females exhibited histone acetylation
      alterations at bdnf I or reelin. These data demonstrate the ability of
      maltreatment to have long-term consequences on histone acetylation in the mPFC,
      and provide further evidence of the epigenetic susceptibility of bdnf IV to the
      quality of infant-caregiver experiences. 

PMID- 26305289
TI  - Pitch perception and frequency-following responses elicited by lexical-tone
      chimeras.
AB  - OBJECTIVE: Previous research has shown the usefulness of utilizing auditory
      chimeras in assessing a listener's perception of the envelope and fine structure
      for an acoustic stimulus. However, research comparing and contrasting behavioral
      and electrophysiological responses to this stimulus type is scarce. DESIGN: Two
      sets of chimeric stimuli were constructed by interchanging the envelopes and fine
      structures of the rising/yi(2)/and falling/yi(4)/Mandarin pitch contours that
      were filtered through 1, 2, 4, 8, 16, 32, and 64 frequency banks. Behavioral
      pitch-perception tasks were administered through a two-alternative, forced-choice
      paradigm. Electrophysiological responses were measured through scalp-recorded
      frequency-following responses (FFRs) to the lexical-tone chimeras. STUDY SAMPLE:
      Twenty American and twenty Chinese adults were recruited. RESULTS: A two-way
      analysis of variance showed significance (p < 0.05) within and across the filter
      bank and language background factors for the behavioral measurements, while the
      frequency-following response demonstrated a significance only across the filter
      banks. CONCLUSIONS: Perceptual importance of envelope cues increases starting
      from 16 filter banks, while the FFR accuracy and magnitude decreases with
      increasing number of filter banks. These results can be useful in assessing
      experience-dependent neuroplasticity and in designing speech processing
      strategies for cochlear-implant users who speak tonal or non-tonal languages
      around the globe.

PMID- 26305290
TI  - The self-relevance system?
AB  - We suggest that the Self Attention Network (SAN) maybe part of a larger self
      regulatory system, which we term the Self-Relevance System (SRS) of which the
      "core" or default network is a major part. It is within the core network that
      memories are generated and the future imagined. Such memories and imaginings are
      the basis of preoccupations. Within the SRS then preoccupations drive the
      emergence of attentional biases (ABs). ABs in turn are modulated by the SAN
      activating and inhibiting circuits that shape behavior. We consider briefly how
      this might function in dysfunctional appetitive behaviors, e.g., substance abuse.

PMID- 26305291
TI  - Programming Tilting Angles in Shape Memory Polymer Janus Pillar Arrays with
      Unidirectional Wetting against the Tilting Direction.
AB  - By coating a thin layer of metal, including gold and gold-palladium alloy, of
      different thickness on the deformed shape memory polymer (SMP) pillars, we
      manipulate the degree of recovery of the SMP pillars. Pillars of different
      tilting angles were obtained as a result of balancing the strain recovery energy
      of the SMP pillars that favor the original straight state and the elastic energy
      of the metal layers that prefer the bent state. With this selective coating of a
      metal layer on the tilted pillars, we report a unique anisotropic liquid
      spreading behavior, where the water droplet is fully pinned in the direction of
      pillar tilting but advances in the reverse direction. This phenomenon is
      explained by the interplay of the surface chemistry and topography. 

PMID- 26305292
TI  - Erratum to: Association between new indices in the locomotive syndrome risk test
      and decline in mobility: third survey of the ROAD study.

PMID- 26305293
TI  - New Insight into Quantitative Modeling of DNA Double-Strand Break Rejoining.
AB  - Accurate and mechanistically plausible mathematical models of DNA double-strand
      break (DSB) rejoining kinetics are needed to correctly estimate the dependence of
      cell death and transformation on linear energy transfer, radiation dose and time.
      When integrated into more comprehensive risk estimation approaches, such models
      are potentially valuable tools in applications such as treatment planning for
      radiotherapy. In this study, we compared 10 DSB rejoining models based on data
      collected from 61 mammalian cell lines after high-dose-rate photon or heavy ion
      irradiation. The set of models included formalisms with: 1. one, two or three
      discrete first-order rejoining rates; 2. continuously distributed first-order
      rejoining rates; and 3. second-order rejoining rates. The Akaike information
      criterion was used to quantify the relative support for each model from the data,
      accounting for goodness of fit and model complexity. The best performance was
      exhibited by a bi-exponential model with two discrete rejoining rates and a model
      with gamma-distribution rejoining rates. Models with more than three free
      parameters overfitted the data and models with single DSB rejoining rates or with
      an inflexible distribution of rejoining rates lacked accuracy. Of special note is
      that the analyzed data provide little support for models that rely on pairwise
      interactions to describe DSB rejoining kinetics. Consequently, kinetic cell
      survival models reflecting bi-exponential DSB rejoining might be preferable to
      models based on the kinetics of intra- and inter-lesion rejoining. 

PMID- 26305295
TI  - Captopril Increases Survival after Whole-Body Ionizing Irradiation but Decreases
      Survival when Combined with Skin-Burn Trauma in Mice.
AB  - Past and recent radiation events have involved a high incidence of radiation
      combined injury where victims often succumb to serious infections as a
      consequence of bacterial translocation and subsequent sepsis. The risk of
      infection is exacerbated in radiation combined skin-burn injury (RCI), which
      increase vulnerability. Furthermore, no suitable countermeasures for radiation
      combined skin-burn injury have been established. In this study, we evaluated
      captopril as a potential countermeasure to radiation combined skin-burn injury.
      Captopril is an FDA-approved angiotensin-converting enzyme inhibitor that was
      previously reported to stimulate hematopoietic recovery after exposure to
      ionizing radiation. Female B6D2F1/J mice were whole-body bilateral (60)Co gamma
      photon irradiated (dose rate of 0.4 Gy/min) with 9.5 Gy (LD70/30 for RCI),
      followed by nonlethal dorsal skin-burn injury under anesthesia (approximately 15%
      total-body surface-area burn). Mice were provided with acidified drinking water
      with or without dissolved captopril (0.55 g/l) for 30 days immediately after
      injury and were administered topical gentamicin (0.1% cream; day 1-10) and oral
      levofloxacin (90-100 mg/kg; day 3-16). Surviving mice were euthanized on day 30
      after analyses of water consumption, body weight and survival. Our data
      demonstrate that, while treatment with captopril did mitigate mortality induced
      by radiation injury (RI) alone (55% captopril vs. 80% vehicle; n = 20, P < 0.05),
      it also resulted in decreased survival after radiation combined skin-burn injury
      (22% captopril vs. 41% vehicle; n = 22, P < 0.05). Moreover, captopril
      administration via drinking water produced an uneven dosage pattern among the
      different injury groups ranging from 74 +/- 5.4 to 115 +/- 2.2 mg/kg/day.
      Captopril treatment also did not counteract the negative alterations in
      hematology, splenocytes or bone marrow cellularity after either radiation injury
      or radiation combined skin-burn injury. These data suggest that captopril may
      exert its actions differently between the two injury models (RI vs. RCI) and that
      captopril dosing, when combined with topical and systemic antibiotic treatments,
      may not be a suitable countermeasure for RCI. 

PMID- 26305296
TI  - Preoperative prediction of inpatient recovery of function after total hip
      arthroplasty using performance-based tests: a prospective cohort study.
AB  - PURPOSE: The aim of this study was to evaluate the value of conventional factors,
      the Risk Assessment and Predictor Tool (RAPT) and performance-based functional
      tests as predictors of delayed recovery after total hip arthroplasty (THA).
      METHOD: A prospective cohort study in a regional hospital in the Netherlands with
      315 patients was attending for THA in 2012. The dependent variable recovery of
      function was assessed with the Modified Iowa Levels of Assistance scale. Delayed
      recovery was defined as taking more than 3 days to walk independently.
      Independent variables were age, sex, BMI, Charnley score, RAPT score and scores
      for four performance-based tests [2-minute walk test, timed up and go test (TUG),
      10-meter walking test (10 mW) and hand grip strength]. RESULTS: Regression
      analysis with all variables identified older age (>70 years), Charnley score C,
      slow walking speed (10 mW >10.0 s) and poor functional mobility (TUG >10.5 s) as
      the best predictors of delayed recovery of function. This model (AUC 0.85, 95% CI
      0.79-0.91) performed better than a model with conventional factors and RAPT
      scores, and significantly better (p = 0.04) than a model with only conventional
      factors (AUC 0.81, 95% CI 0.74-0.87). CONCLUSIONS: The combination of performance
      based tests and conventional factors predicted inpatient functional recovery
      after THA. IMPLICATIONS FOR REHABILITATION: Two simple functional performance
      based tests have a significant added value to a more conventional screening with
      age and comorbidities to predict recovery of functioning immediately after total
      hip surgery. Patients over 70 years old, with comorbidities, with a TUG score
      >10.5 s and a walking speed >1.0 m/s are at risk for delayed recovery of
      functioning. Those high risk patients need an accurate discharge plan and could
      benefit from targeted pre- and postoperative therapeutic exercise programs.

PMID- 26305294
TI  - Treating Brain Tumor with Microbeam Radiation Generated by a Compact Carbon
      Nanotube-Based Irradiator: Initial Radiation Efficacy Study.
AB  - Microbeam radiation treatment (MRT) using synchrotron radiation has shown great
      promise in the treatment of brain tumors, with a demonstrated ability to
      eradicate the tumor while sparing normal tissue in small animal models. With the
      goal of expediting the advancement of MRT research beyond the limited number of
      synchrotron facilities in the world, we recently developed a compact laboratory
      scale microbeam irradiator using carbon nanotube (CNT) field emission-based X-ray
      source array technology. The focus of this study is to evaluate the effects of
      the microbeam radiation generated by this compact irradiator in terms of tumor
      control and normal tissue damage in a mouse brain tumor model. Mice with U87MG
      human glioblastoma were treated with sham irradiation, low-dose MRT, high-dose
      MRT or 10 Gy broad-beam radiation treatment (BRT). The microbeams were 280 MUm
      wide and spaced at 900 MUm center-to-center with peak dose at either 48 Gy (low
      dose MRT) or 72 Gy (high-dose MRT). Survival studies showed that the mice treated
      with both MRT protocols had a significantly extended life span compared to the
      untreated control group (31.4 and 48.5% of life extension for low- and high-dose
      MRT, respectively) and had similar survival to the BRT group. Immunostaining on
      MRT mice demonstrated much higher DNA damage and apoptosis level in tumor tissue
      compared to the normal brain tissue. Apoptosis in normal tissue was significantly
      lower in the low-dose MRT group compared to that in the BRT group at 48 h
      postirradiation. Interestingly, there was a significantly higher level of cell
      proliferation in the MRT-treated normal tissue compared to that in the BRT
      treated mice, indicating rapid normal tissue repairing process after MRT.
      Microbeam radiation exposure on normal brain tissue causes little apoptosis and
      no macrophage infiltration at 30 days after exposure. This study is the first
      biological assessment on MRT effects using the compact CNT-based irradiator. It
      provides an alternative technology that can enable widespread MRT research on
      mechanistic studies using a preclinical model, as well as further translational
      research towards clinical applications. 

PMID- 26305297
TI  - Multifunctional nanoreactor for comprehensive characterization of membrane
      proteins based on surface functionalized mesoporous foams.
AB  - An integrated protocol is proposed here for efficient analysis of membrane
      proteins based on surface functionalized mesoporous graphene foams (MGF). The
      inherent hydrophobic nature of MGF and surface modification with hydrophilic
      chitosan (CS) make it highly suitable for the enrichment of hydrophobic membrane
      proteins from organic solvent, while remaining well-dispersed in aqueous solution
      for subsequent proteolysis. Therefore, such a multifunctional reactor ensures a
      facile solvent adjustment route. Furthermore, as a chitosan modified nanoporous
      reactor, it also provides a biocompatible nanoenvironment that can maintain the
      stability and activity of enzymes to realize efficient in situ digestion of the
      enriched membrane proteins. The concept was first proved with a standard
      hydrophobic membrane protein, bacteriorhodopsin, where a high number of
      identified peptides and amino acid sequence coverage were achieved even at
      extremely low protein concentration. The mesoporous reaction system was further
      applied to the analysis of complex real-case proteome samples, where 931 membrane
      proteins were identified in triplicate analyses by 2D LC-MS/MS. In contrast, with
      in-solution proteolysis, only 73 membrane proteins were identified from the same
      sample by the same 2D LC-MS/MS. The identified membrane proteins by the MGF-CS
      protocol include many biomarkers of the cell line. These results suggest that the
      multifunctional MGF-CS protocol is of great value to facilitate the comprehensive
      characterization of membrane proteins in the proteome research. 

PMID- 26305298
TI  - Risks in Randomized Controlled Trials: Role of Interim Analysis and Data
      Monitoring Committee.

PMID- 26305299
TI  - Morphological and Topographical Anatomy of Diaphyseal Nutrient Foramina of Dried
      Pakistani Fibulae.
AB  - OBJECTIVE: To study the diaphyseal Nutrient Foramina (NF) of dry Pakistani
      fibulae morphometrically and topographically. STUDY DESIGN: Descriptive cross
      sectional study. PLACE AND DURATION OF STUDY: Anatomy Department, Allama Iqbal
      Medical College, Lahore, from December 2013 to April 2014. METHODOLOGY: The
      materials comprised 168 dried fibulae, 80 of left side and 88 of right side.
      Length of bone and distance of NF from the proximal end was calculated by placing
      bones on osteometric board. The Foramen Index (FI) was calculated by applying the
      Hughes formula, dividing the distance of the foramen from the proximal end (DNF)
      by the total length of the bone (TL) which was multiplied by hundred FI =
      (DNF/TL) x 100. RESULTS: Eighty five bones (96.6%) of right side and 79 bones
      (98.8%) of left side had a single nutrient foramen. Mean length of left fibula
      was 34.690 +/-2.353 cms and of right fibula 34.905 +/-2.198 cms. Mean foramen
      index was 47.651 +/-7.601 on the left side and 50.283 +/-11.478 on the right
      side. In the right fibulae, type-1 foramen was present in one (1.13%) bone, type
      2 was present in 77 (87.5%) bones and type-3 was found in 10 (11.36%) bones. In
      the left fibulae, type-1 foramen was not found in any bone, type-2 in 79 bones
      (98.75%) and type 3 in only 1 bone (1.25%). CONCLUSION: This study provides
      important information on the topography of nutrient foramina of fibula in
      Pakistani population. As microvascular bone transfer is becoming more popular,
      such data regarding nutrient foramina will be of importance to orthopaedic
      surgeons.

PMID- 26305300
TI  - Targeted Ultrasound of an Indeterminate Breast Lesion on Mammography: When Does
      It Influence Management?
AB  - OBJECTIVE: To determine the change over mammographic diagnosis, BI-RADS category
      and management following targeted ultrasound of an indeterminate lesion seen on
      mammography and associated factors, if any. STUDY DESIGN: Descriptive, analytical
      study. PLACE AND DURATION OF STUDY: Radiology Department, The Aga Khan University
      Hospital and Clifton Medical Services, Karachi, from April 2010 to May 2011.
      METHODOLOGY: Patients referred for targeted breast ultrasound following X-ray
      mammography were selected regardless of age. Targeted Ultrasound (TUS) was
      defined as a limited ultrasound of a specific lesion or breast part as indicated
      by the referring source. Comparison was made between the post mammography and
      post TUS lesion characterization, diagnosis and BI-RADS category (0-5) which was
      taken as a measure of management change. Those were evaluated to determine
      significance of age, marital status, parity, breast parenchymal pattern ( dense,
      fatty, heterogeneous), referring source for the TUS (radiology resident,
      radiologist or surgeon), lesion characteristics (density, echogenecity, shape,
      location, margins, size, depth-to-width ratio, enhancement or shadowing),
      presenting symptoms or signs and reason for TUS. Ap-value of 0.05 or less was
      taken as significant. RESULTS: There were a total of 342 patients with mean age
      of 49.7 +/-13.5 years. It assigned a definite category in 232 patients with an
      indefinite category (0) on mammography requiring further investigation. It
      decreased the suspicion for malignancy in 180 (77.58%) by assigning a low BI-RADS
      category and increased the suspicion in 52 (22.41%). The factors significantly
      associated with this changes included clinical indication being diagnostic (p <
      0.001), lesion characteristics on imaging (p < 0.001), heterogenous breast
      parenchymal pattern (p < 0.001) and presence of known risk factors (p=0.049).
      CONCLUSION: TUS served as a problem solving tool in the evaluation and management
      of an indeterminate breast lesion in a high number of patients, particularly when
      there was a lump as indication for imaging in the presence of risk factors in a
      patient with otherwise heterogeneously dense breast parenchyma.

PMID- 26305301
TI  - Effectiveness of Quantitative Real Time PCR in Long-Term Follow-up of Chronic
      Myeloid Leukemia Patients.
AB  - OBJECTIVE: To determine the use of the Quantitative Real Time PCR (RQ-PCR) assay
      follow-up with Chronic Myeloid Leukemia (CML) patients. STUDY DESIGN: Cross
      sectional observational. PLACE AND DURATION OF STUDY: Izmir Ataturk Education and
      Research Hospital, Izmir, Turkey, from 2009 to 2013. METHODOLOGY: Cytogenetic,
      FISH, RQ-PCR test results from 177 CMLpatients' materials selected between 2009 -
      2013 years was set up for comparison analysis. Statistical analysis was performed
      to compare between FISH, karyotype and RQ-PCR results of the patients.
      Karyotyping and FISH specificity and sensitivity rates determined by ROC analysis
      compared with RQ-PCR results. Chi-square test was used to compare test failure
      rates. RESULTS: Sensitivity and specificity values were determined for
      karyotyping 17.6 - 98% (p=0.118, p > 0.05) and for FISH 22.5 - 96% (p=0.064, p >
      0.05) respectively. FISH sensitivity was slightly higher than karyotyping but
      there was calculated a strong correlation between them (p < 0.001). RQ-PCR test
      failure rate did not correlate with other two tests (p > 0.05); however,
      karyotyping and FISH test failure rate was statistically significant (p < 0.001).
      CONCLUSION: Besides, the situation needed for karyotype analysis, RQ-PCR assay
      can be used alone in the follow-up of CMLdisease.

PMID- 26305302
TI  - Molecular Distribution of Deafness Loci in Various Ethnic Groups of the Punjab,
      Pakistan.
AB  - OBJECTIVE: To determine the existence of autosomal recessive deafness loci in
      different ethnic tribes of the Punjab. STUDY DESIGN: Descriptive observational
      study. PLACE AND DURATION OF STUDY: Department of Human Genetics and Centre of
      Excellence in Molecular Biology, University of Health Sciences, Lahore, from July
      2009 to March 2012. METHODOLOGY: Healthy willing subjects with autosomal
      recessive deafness loci were studied for selected deafness loci. Those who were
      unhealthy and gave history of infectious disease were excluded. DNAextraction was
      carried out using the inorganic method. Fluorescently labeled microsatellite
      markers were used for amplification of desired regions by PCR (Polymerase Chain
      Reaction). Automated allele assignment was performed using the ABI PRISM GeneScan
      Analysis Software Version 3.7 for Windows NTPlatform. Two-point LOD scores were
      calculated using the FASTLINK computer package (Schaffer 1996) and MLINK was used
      for calculation and 95% CI (confidence intervals) were calculated. RESULTS: One
      hundred and thirty two individuals of 8 families were analyzed. Three families
      (SAPun-03, SAPun-10 and SAPun-15) were found linked to DFNB12; two families
      (SAPun-05 and SAPun-17) were found linked to DFNB8/10, while three families
      (SAPun-06, SAPun-13 and SAPun-19) were found linked to DFNB29, DFNB36 and DFNB37
      respectively. CONCLUSION: The genotyping results revealed that DFNB12 locus was
      the most common followed by DFNB8/10 locus, while the Loci DFNB29, DFNB36 and
      DFNB37 were less common.

PMID- 26305303
TI  - A Simplified MCQs Interpretation Guide for Faculty.
AB  - OBJECTIVE: To devise a guide for faculty to interpret Psychometric Analysis of
      MCQs followed by its assessment. STUDY DESIGN: Across-sectional study. PLACE AND
      DURATION OF STUDY: Shifa College of Medicine, Islamabad, from January to July
      2009. METHODOLOGY: A simplified interpretation guide comprising of a visual
      format and an interpretive summary was designed for faculty members to help them
      understand the item analysis of the MCQs in an uncomplicated way. A feedback from
      the faculty was obtained after administration to see the results. RESULTS: Eighty
      five percent of course coordinators (n=14) agreed that they could understand the
      MCQ analysis. Eight percent (n=3) faculty strongly, while 82% (n=13) agreed that
      analysis is helping them to refine the process of MCQ making. Forty five percent
      (n=7) faculty agreed that analysis of MCQ was helpful in identifying knowledge
      gaps in students. All the course coordinators agreed that they found the revised
      format easy to understand. CONCLUSION: The faculty found the interpretation guide
      for MCQs user-friendly and helpful.

PMID- 26305304
TI  - Feeding of Low Birth Weight Newborns in Tertiary Care Hospitals in Pakistan: Do
      They Follow the World Health Organization Latest Guidelines?
AB  - OBJECTIVE: To determine the extent the World Health Organization (WHO) guidelines
      on the care of Low Birth Weight (LBW) newborns are followed in Pakistani
      hospitals and analyze any difference in policy compliance between different
      hospitals. STUDY DESIGN: Descriptive analytical study. PLACE AND DURATION OF
      STUDY: Data was collected from five tertiary care hospitals, one each from
      Peshawar, Lahore, Quetta, Karachi and Islamabad, from January to June 2012.
      METHODOLOGY: LBW newborns data derived from medical records was used. It was
      collected using a questionnaire, which encompassed the recent WHO recommendations
      for feeding of LBW. Twenty questionnaires were collected from each hospital.
      STATA11.0 was used to analyze the data. RESULTS: Fifty seven LBW newborns (57%)
      were fed with mother's own milk, and 9 (9%) were fed on donor human milk. Forty
      four newborns (44%) were initiated breastfeeding within the first hour after
      birth. Most of the babies not able to be breastfed were fed with intra gastric
      tube. Feeding practices varied markedly across hospitals, ranging from one
      hospital where all newborns were fed formula milk to one where all were fed
      breast milk. CONCLUSION: The WHO guidelines were only partially implemented, with
      significant differences between hospitals in level of implementation of
      recommended practices. Given the benefits expected from the application of the
      guidelines, efforts should be made for the establishment and promotion of a
      single national policy for LBW feeding that follows the WHO new guidelines and
      streamlines the LBW feeding practices across the country.

PMID- 26305305
TI  - Symptomatic Surgically Treated Non-neoplastic Cysts of the Central Nervous
      System: A Clinicopathological Study From Pakistan.
AB  - OBJECTIVE: To report clinicopathologic features of symptomatic surgically removed
      non-neoplastic cysts of the central nervous system (CNS). STUDY DESIGN: Case
      series. PLACE AND DURATION OF STUDY: The Aga Khan University Hospital, Karachi,
      from 2003 to 2012. METHODOLOGY: All non-neoplastic CNS cysts reported during the
      study period were retrieved and reviewed. Age, gender, location, histologic type
      and clinical features were noted. RESULTS: A total of 124 cysts were diagnosed in
      the study period. These included 44 epidermoid cysts (mean age 30.5 +/- 13.8
      years), 35 colloid cysts (mean age 31 +/-13.2 years), 32 arachnoid cysts (mean
      age 24.8 +/-20.2 years), 6 dermoid cysts, 3 enterogenous cysts and Rathke's cleft
      cysts each and 1 ependymal cyst. All cyst types mainly presented in young adults
      in both genders with signs and symptoms of a mass lesion. CONCLUSION: Non
      neoplastic cyst mainly presented like a CNS mass lesion in young adults.
      Epidermoids were the most common type of these cysts in the present series
      followed by the colloid and the arachnoid cysts.

PMID- 26305306
TI  - Single Incision Pediatric Endoscopic Surgery: Advantages of a Relatively Large
      Incision.
AB  - OBJECTIVE: To describe Single Incision Pediatric Endoscopic Surgery (SIPES)
      performed on children with various diagnoses, emphasizing its advantages. STUDY
      DESIGN: An observational case series. PLACE AND DURATION OF STUDY: Department of
      Pediatric Surgery, Dr. Sami Ulus Maternity and Child Health Hospital, Ankara,
      Turkey, from January 2011 to November 2014. METHODOLOGY: A review of patient
      charts was conducted in which SIPES was preferred as the surgical procedure.
      Patient demographics, operative details, operative time, clinical outcomes,
      postoperative pain and cosmesis were analyzed. RESULTS: SIPES was performed on 45
      patients (21 girls, 24 boys). Thirty-three appendectomies, 5 varicocelectomies, 3
      oophorectomies, 2 ovarian and one paratubal cyst excision, and one fallopian tube
      excision were performed. All except one procedures were performed through our
      standard 2 cm umbilical vertical or smile incision. In 18 cases, abdominal
      irrigation/aspiration was easily performed through the existing larger incision,
      as is done with open surgical technique. None of the patients had early
      postoperative shoulder/back pain since complete disinflation of CO2could be
      ensured. All of the patients/parents were satisfied with the cosmesis.
      CONCLUSION: SIPES has the advantages of limiting the surgical scar to within the
      umbilicus and providing easy disinflation of CO2, allowing intraabdominal
      cleaning and extraction of large volume tissue samples through a single large
      umbilical incision.

PMID- 26305307
TI  - Comparison of the Therapeutic Effects of Thymoquinone and Methotrexate on Renal
      Injury in Pristane Induced Arthritis in Rats.
AB  - OBJECTIVE: To determine the effect of thymoquinone and methotrexate on blood urea
      and serum creatinine in arthritic rats. STUDY DESIGN: Experimental, comparative
      study. PLACE AND DURATION OF STUDY: Postgraduate Medical Institute, Lahore, from
      March to August 2013. METHODOLOGY: Thirty two female Sprague-Dawley rats were
      randomized into four equal groups (n=8); group A(healthy control), group B
      (positive control), group C (Thymoquinone treated) and group D (Methotrexate
      treated). Arthritis developed within two weeks after a single pristane injection.
      Total leukocyte count, blood urea and serum creatinine were taken at day 0, 15
      and 30. While clinical score of inflammation was taken at day 0 and then on every
      alternate day. RESULTS: Development of arthritis and renal involvement was
      accompanied by significant raise in total leukocyte count, clinical score of
      inflammation, blood urea and serum creatinine as compared to healthy control rats
      (group A) till day 15 (p < 0.001). From day 15 to day 30 both thymoquinone (group
      C) and methotrexate (group D) significantly lowered the total leukocyte count,
      clinical score of inflammation and improved blood urea and serum creatinine as
      compared to arthritic rats (group B) (p < 0.001). Methotrexate was found a bit
      more effective than thymoquinone. CONCLUSION: Evaluation of results supported the
      beneficial effects of thymoquinone in renal injury produced by rheumatoid
      arthritis.

PMID- 26305308
TI  - Clinical Effect of Percutaneous Radiofrequency Ablation for Residual Lung
      Metastases from Breast Cancer After Systemic Chemotherapy.
AB  - OBJECTIVE: To determine the clinical effect of Radiofrequency Ablation (RFA) for
      residual lung metastases from breast cancer after systemic chemotherapy. STUDY
      DESIGN: An experimental study. PLACE AND DURATION OF STUDY: The Second Affiliated
      Hospital of Soochow University, Suzhou, Fudan University Shanghai Cancer Center,
      Shanghai, China, from January 2008 to October 2014. METHODOLOGY: Thirty-five
      breast cancer patients with 67 pulmonary metastases were involved in this study.
      All lesions were treated by RFA and followed by CT-scan. Primary endpoint of this
      clinical study was local control; secondary endpoints were overall survival and
      treatment-related toxicities. RESULTS: Complete Response (CR) was observed in 59
      lesions, with Partial Response (PR) in 4 lesions, Stable Disease (SD) in 1 lesion
      and Progression Disease (PD) in 3 lesions. The lesion diameter > 2 cm was related
      to poor local control (p=0.04). The median Overall Survival (OS) was 33 months
      (95%CI: 21.6 - 44.4). One-, 2-, and 3-year OS rates were 88.6%, 59.3% and 42.8%
      respectively. The mumber of pulmonary metastases (>=2), the diameter of lesion (>
      2 cm) and coexisting with liver metastases were significantly correlated to poor
      OS by multivariate analysis. Log-rank test showed statistically significant
      difference of OS in diameter of lesion and coexisting with other metastases.
      CONCLUSION: RFA is a promising treatment option for patients with residual lung
      metastases from breast cancer after systemic chemotherapy in selected patients.

PMID- 26305309
TI  - Complementary LC-MS/MS Proteomic Analysis of Uremic Plasma Proteins.
AB  - OBJECTIVE: To complement an earlier analysis of protein alterations in plasma
      from uremic versus healthy subjects by addition of further LC-MS/MS analysis to
      the previously used MALDI-TOF mass analyses. METHODOLOGY: Sequence
      identifications of tryptic peptides from SDS gel electrophoretic fractions of
      immunodepleted and HPLC-fractionated plasma was performed from seven chronic
      kidney disease stage 5 patients (age 55 +/- 14 years, glomerular filtration rate
      6.9 +/-2.9 mL/minute/1.73 m2) and from seven matched controls. RESULTS: About
      twice as many proteins were increased in uremic plasma as the previously
      identified. The identifications included proteins that consistently complement
      the two identification patterns regarding separate subunits from the same protein
      complex. CONCLUSION: Mass spectrometric analysis is applicable to complex plasma
      proteomes in clinical settings. The LC-MS/MS technique, based on individual
      peptide sequence analyses, gives increased identifications and also demonstrates
      feasibility of this technique in clinical practice.

PMID- 26305310
TI  - Paediatric Percutaneous Nephrolithotomy (PCNL).
AB  - OBJECTIVE: To describe Paediatric Percutaneous Nephrolithotomy (PCNL) in terms of
      safety and efficacy in a group of 26 children. STUDY DESIGN: An observational
      study. PLACE AND DURATION OF STUDY: Shifa International Hospital, Islamabad, from
      January 2011 to June 2013. METHODOLOGY: PCNL of 26 children was done by standard
      technique. The patients were analyzed for age, gender, presenting symptoms, stone
      size, site, PCNL approach, operative time, stone clearance, hospital stay and per
      operative and postoperative complications. Descriptive statistics were obtained.
      RESULTS: The mean age was 9.21 +/-5.70 years. Seventeen (65.4%) patients were
      male whereas 9 (34.6%) patients were female. Flank pain was the most common
      presenting symptom. Mean stone size was 2.21 +/-1.04 cm. Mean operative time was
      158.8 +/-39.63 minutes and mean hospital stay was 2.84 +/-1.14 days.
      Postoperative transfusion was required in only one case (4%). There was no
      episode of sepsis or perinephric collection. Per-operative stone clearance was
      93.28% +/- 9.23%. Conversion to open was seen in one (4%) case. DJ stent was
      placed in 7 (27%) cases. CONCLUSION: PCNL is a safe and effective way of treating
      renal stones in paediatric age group.

PMID- 26305311
TI  - Parotid Abscess with Involvement of Facial Nerve Branches.
AB  - Facial nerve paresis is only rarely seen with benign diseases of the parotid
      gland. A 22-year male had muscle loss in the preauricular region of the right
      side of his face that extended towards the mandibular angle for the last 6
      months. The neurological examination did not reveal any pathology other than
      right preauricular region muscle atrophy that was limited by the mandibular
      angle. The Electroneuronography (EnoG) provided a ratio of 55.38%, compared the
      affected side to left side. Ultrasonography of the defined region showed two mass
      lesions 13.5 x 7 mm and 10 x 5 mm in size in the anteromedial section of the
      right parotid gland that were close to each other, without internal calcific
      foci, and heterogenous hyperechogenic structure without internal vascularization.
      Fine needle aspiration obtained many polymorphonuclear leukocytes, cell debris, a
      few mononuclear inflammatory cells and many crystalloid structures. The lesion
      was diagnosed as a parotid abscess. Antibiotic treatment was started for the
      parotid gland abscess.

PMID- 26305312
TI  - Subdural Hematomas Following Intracranial Aneurysm Rupture: A Rare Phenomenon.
AB  - Acute Subdural Hematoma (aSDH) due to aneurysm rupture and no subarachnoid
      bleeding are very rare with only 29 cases reported in literature. A 56-year
      female presented with headache and drowsiness and a previous history of loss of
      consciousness. Clinical examination revealed a GCS of 14 and a right sided
      hemiparesis. Workup revealed a pure subdural hematoma due to a middle cerebral
      artery aneurysm rupture with no subarachnoid hemorrhage. Laboratory workup was
      otherwise normal and she had no history of falls or head trauma consistent with
      the usual etiology of an aSDH. She underwent evacuation of the hematoma with
      clipping of the aneurysm. She had an uneventful recovery with good outcome and no
      residual neurological deficits at one-year follow-up.

PMID- 26305313
TI  - Unilateral Ectrodactyly in a Newborn with Trisomy 18 Syndrome: An Unusual
      Association.
AB  - The case of a newborn male with trisomy 18 syndrome, having bilateral syndactyly,
      aplasia and hypoplasia of the foot digits, unilateral ectrodactyly of the left
      foot and a prominently dorsiflexed hallux, clenched hand with overlapping fingers
      and general hypertonia, is presented. There are only 5 cases of trisomy 18
      syndrome associated with ectrodactyly in the literature. We present a case of
      trisomy 18 syndrome with unilateral ectrodactyly of the left foot, which is an
      infrequent association. 

PMID- 26305314
TI  - A New Born with Lamellar ichthyosis(Collodion Baby).
AB  - Ichthyosisis an infrequent clinical entity worldwide with an incidence of
      1:600,000 births. It can be one of the two types: collodion baby and Harlequin
      fetus or malignant keratoma (most severe form). The clinical manifestations in
      either form are thick and hard skin with deep splits. Affected babies are born in
      a collodion membrane, a shiny waxy outer layer to the skin that is shed 10 - 14
      days after birth, revealing the main symptom of the disease. The reported case is
      of a neonate, born to primigravida mother at seven and a half month's gestation
      with a birth weight of 2160 grams and Apgar score of 6/10 and 8/10 at 1 and 5
      minutes respectively. Conclusively, early diagnosis of this condition can help
      cope and prevent serious morbidity or even mortality at time. These newborns
      should be monitored carefully in intensive care units by a multi-disciplinary
      team. 

PMID- 26305315
TI  - Content Validity of a Tool Measuring Medication Errors.
AB  - The objective of this study was to determine content and face validity of a tool
      measuring medication errors among nursing students in baccalaureate nursing
      education. Data was collected from the Aga Khan University School of Nursing and
      Midwifery (AKUSoNaM), Karachi, from March to August 2014. The tool was developed
      utilizing literature and the expertise of the team members, expert in different
      areas. The developed tool was then sent to five experts from all over Karachi for
      ensuring the content validity of the tool, which was measured on relevance and
      clarity of the questions. The Scale Content Validity Index (S-CVI) for clarity
      and relevance of the questions was found to be 0.94 and 0.98, respectively. The
      tool measuring medication errors has an excellent content validity. This tool
      should be used for future studies on medication errors, with different study
      populations such as medical students, doctors, and nurses. 

PMID- 26305316
TI  - Screening for G6PD Deficiency Among Neonates with Neonatal Jaundice Admitted to
      Tertiary Care Center: A Need in Disguise.
AB  - This study was conducted to determine the association of Glucose-6-Phosphate
      Dehydrogenase (G-6-PD) deficiency among neonates admitted with jaundice at the
      neonatal intensive care unit, well baby nursery and neonatal step down nursery of
      the Aga Khan University Hospital, Karachi, Pakistan, from January to June 2010. A
      total of 205 neonates following the selection criteria were included. All
      selected neonates have their venous blood drawn, saved in EDTA bottle and sent to
      laboratory of The Aga Khan University Hospital (AKUH). The laboratory results of
      whether G-6-PD deficiency was present or not was recorded in the proforma. G-6-PD
      was deficient in 19 neonates (9.3%). All neonates were male.

PMID- 26305317
TI  - Delayed Recovery From General Anaesthesia due to Severe Hypoglycemia in a Non
      diabetic Adult.

PMID- 26305318
TI  - Dentist-Urologist Interplay in the Dental Management of Penile Prosthesis
      Patient.

PMID- 26305319
TI  - Granulomatous Osteomyelitis of Third Metacarpal Bone as a Sequel to Percutaneous
      Injury on Left Hand Due to Sharp Dental Bur: A Self Reported Case.

PMID- 26305320
TI  - When parents talk about college drinking: an examination of content, frequency,
      and associations with students' dangerous drinking.
AB  - This project examines alcohol messages exchanged between college students and
      their parents, as well as how such messages associate with college students'
      dangerous drinking. Undergraduate students ages 18 to 25 years were recruited for
      the study and asked to recruit a parent. The sample included 198 students and 188
      parents, all of whom completed an online survey. This study found parents tended
      to emphasize the negative aspects of drinking, particularly the dangers of
      drinking and driving and the academic consequences of too much partying. Results
      indicated that parent-student alcohol communication has various dimensions,
      including negative aspects of drinking, rules about drinking, drinking in
      moderation, and benefits of drinking. Parents' reports of discussing alcohol
      rules had a significant, negative association with students' alcohol consumption,
      whereas parents' reports of discussing the negative aspects of alcohol use had
      significant, positive associations with students' dangerous drinking. 

PMID- 26305321
TI  - Outlier detection and removal improves accuracy of machine learning approach to
      multispectral burn diagnostic imaging.
AB  - Multispectral imaging (MSI) was implemented to develop a burn tissue
      classification device to assist burn surgeons in planning and performing
      debridement surgery. To build a classification model via machine learning,
      training data accurately representing the burn tissue was needed, but assigning
      raw MSI data to appropriate tissue classes is prone to error. We hypothesized
      that removing outliers from the training dataset would improve classification
      accuracy. A swine burn model was developed to build an MSI training database and
      study an algorithm's burn tissue classification abilities. After the ground-truth
      database was generated, we developed a multistage method based on Z -test and
      univariate analysis to detect and remove outliers from the training dataset.
      Using 10-fold cross validation, we compared the algorithm's accuracy when trained
      with and without the presence of outliers. The outlier detection and removal
      method reduced the variance of the training data. Test accuracy was improved from
      63% to 76%, matching the accuracy of clinical judgment of expert burn surgeons,
      the current gold standard in burn injury assessment. Given that there are few
      surgeons and facilities specializing in burn care, this technology may improve
      the standard of burn care for patients without access to specialized facilities.

PMID- 26305322
TI  - Impaired ILK Function Is Associated with Deficits in Hippocampal Based Memory and
      Synaptic Plasticity in a FASD Rat Model.
AB  - Fetal Alcohol Spectrum Disorder (FASD) is an umbrella term that encompasses a
      wide range of anatomical and behavioral problems in children who are exposed to
      alcohol during the prenatal period. There is no effective treatment for FASD,
      because of lack of complete characterization of the cellular and molecular
      mechanisms underlying this condition. Alcohol has been previously characterized
      to affect integrins and growth factor signaling receptors. Integrin Linked Kinase
      (ILK) is an effector of integrin and growth-factor signaling which regulates
      various signaling processes. In FASD, a downstream effector of ILK, Glycogen
      Synthase Kinase 3beta (GSK3beta) remains highly active (reduced Ser9
      phosphorylation). GSK3beta has been known to modulate glutamate receptor
      trafficking and channel properties. Therefore, we hypothesize that the cognitive
      deficits accompanying FASD are associated with impairments in the ILK signaling
      pathway. Pregnant Sprague Dawley rats consumed a "moderate" amount of alcohol
      throughout gestation, or a calorie-equivalent sucrose solution. Contextual fear
      conditioning was used to evaluate memory performance in 32-33-day-old pups.
      Synaptic plasticity was assessed in the Schaffer Collateral pathway, and
      hippocampal protein lysates were used to evaluate ILK signaling. Alcohol exposed
      pups showed impaired contextual fear conditioning, as compared to control pups.
      This reduced memory performance was consistent with decrease in LTP as compared
      to controls. Hippocampal ILK activity and GSK3beta Ser21/9 phosphorylation were
      significantly lower in alcohol-exposed pups than controls. Increased synaptic
      expression of GluR2 AMPA receptors was observed with immunoprecipitation of post
      synaptic density protein 95 (PSD95). Furthermore, immunoprecipitation of ILK
      revealed a decreased interaction with GluR2. The ILK pathway appears to play a
      significant role in memory and synaptic plasticity impairments in FASD rats.
      These impairments appear to be mediated by reduced GSK3beta regulation and
      increased synaptic stabilization of the calcium-impermeable GluR2 AMPA receptors.

PMID- 26305324
TI  - Assessing Fishers' Support of Striped Bass Management Strategies.
AB  - Incorporating the perspectives and insights of stakeholders is an essential
      component of ecosystem-based fisheries management, such that policy strategies
      should account for the diverse interests of various groups of anglers to enhance
      their efficacy. Here we assessed fishing stakeholders' perceptions on the
      management of Atlantic striped bass (Morone saxatilis) and receptiveness to
      potential future regulations using an online survey of recreational and
      commercial fishers in Massachusetts and Connecticut (USA). Our results indicate
      that most fishers harbored adequate to positive perceptions of current striped
      bass management policies when asked to grade their state's management regime.
      Yet, subtle differences in perceptions existed between recreational and
      commercial fishers, as well as across individuals with differing levels of
      fishing experience, resource dependency, and tournament participation.
      Recreational fishers in both states were generally supportive or neutral towards
      potential management actions including slot limits (71%) and mandated circle
      hooks to reduce mortality of released fish (74%), but less supportive of reduced
      recreational bag limits (51%). Although commercial anglers were typically less
      supportive of management changes than their recreational counterparts, the
      majority were still supportive of slot limits (54%) and mandated use of circle
      hooks (56%). Our study suggests that both recreational and commercial fishers are
      generally supportive of additional management strategies aimed at sustaining
      healthy striped bass populations and agree on a variety of strategies. However,
      both stakeholder groups were less supportive of harvest reductions, which is the
      most direct measure of reducing mortality available to fisheries managers. By
      revealing factors that influence stakeholders' support or willingness to comply
      with management strategies, studies such as ours can help managers identify
      potential stakeholder support for or conflicts that may result from regulation
      changes. 

PMID- 26305323
TI  - Processed and Unprocessed Red Meat and Risk of Colorectal Cancer: Analysis by
      Tumor Location and Modification by Time.
AB  - Although the association between red meat consumption and colorectal cancer (CRC)
      is well established, the association across subsites of the colon and rectum
      remains uncertain, as does time of consumption in relation to cancer development.
      As these relationships are key for understanding the pathogenesis of CRC, they
      were examined in two large cohorts with repeated dietary measures over time, the
      Nurses' Health Study (n = 87,108 women, 1980-2010) and Health Professionals
      Follow-up Study (n = 47,389 men, 1986-2010). Cox proportional hazards regression
      models generated hazard ratios (HRs) and 95% confidence intervals (CIs), which
      were pooled by random-effects meta-analysis. In combined cohorts, there were
      2,731 CRC cases (1,151 proximal colon, 816 distal colon, and 589 rectum). In
      pooled analyses, processed red meat was positively associated with CRC risk (per
      1 serving/day increase: HR = 1.15, 95% CI: 1.01-1.32; P for trend 0.03) and
      particularly with distal colon cancer (per 1 serving/day increase; HR = 1.36; 95%
      CI: 1.09-1.69; P for trend 0.006). Recent consumption of processed meat (within
      the past 4 years) was not associated with distal cancer. Unprocessed red meat was
      inversely associated with risk of distal colon cancer and a weak non-significant
      positive association between unprocessed red meat and proximal cancer was
      observed (per 1 serving/day increase: distal HR = 0.75; 95% CI: 0.68-0.82; P for
      trend <0.001; proximal HR = 1.14, 95% CI: 0.92-1.40; P for trend 0.22). Thus, in
      these two large cohorts of US health professionals, processed meat intake was
      positively associated with risk of CRC, particularly distal cancer, with little
      evidence that higher intake of unprocessed red meat substantially increased risk
      of CRC. Future studies, particularly those with sufficient sample size to assess
      associations by subsites across the colon are needed to confirm these findings
      and elucidate potentially distinct mechanisms underlying the relationship between
      processed meat and subtypes of unprocessed red meat with CRC. 

PMID- 26305325
TI  - The Molecular Signature of HIV-1-Associated Lipomatosis Reveals Differential
      Involvement of Brown and Beige/Brite Adipocyte Cell Lineages.
AB  - Highly active antiretroviral therapy has remarkably improved quality of life of
      HIV-1-infected patients. However, this treatment has been associated with the so
      called lipodystrophic syndrome, which conveys a number of adverse metabolic
      effects and morphological alterations. Among them, lipoatrophy of subcutaneous
      fat in certain anatomical areas and hypertrophy of visceral depots are the most
      common. Less frequently, lipomatous enlargements of subcutaneous fat at distinct
      anatomic areas occur. Lipomatous adipose tissue in the dorso-cervical area
      ("buffalo hump") has been associated with a partial white-to-brown phenotype
      transition and with increased cell proliferation, but, to date, lipomatous
      enlargements arising in other parts of the body have not been characterized. In
      order to establish the main molecular events associated with the appearance of
      lipomatosis in HIV-1 patients, we analyzed biopsies of lipomatous tissue from
      "buffalo hump" and from other anatomical areas in patients, in comparison with
      healthy subcutaneous adipose tissue, using a marker gene expression approach.
      Both buffalo-hump and non-buffalo-hump lipomatous adipose tissues exhibited
      similar patterns of non-compromised adipogenesis, unaltered inflammation, non
      fibrotic phenotype and proliferative activity. Shorter telomere length, prelamin
      A accumulation and SA-beta-Gal induction, reminiscent of adipocyte senescence,
      were also common to both types of lipomatous tissues. Buffalo hump biopsies
      showed expression of marker genes of brown adipose tissue (e.g. UCP1) and,
      specifically, of "classical" brown adipocytes (e.g. ZIC1) but not of beige/brite
      adipocytes. No such brown fat-related gene expression occurred in lipomatous
      tissues at other anatomical sites. In conclusion, buffalo hump and other
      subcutaneous adipose tissue enlargements from HIV-1-infected patients share a
      similar lipomatous character. However, a distorted induction of white-to
      "classical brown adipocyte" phenotype appears unique of dorso-cervical
      lipomatosis. Thus, the insults caused by HIV-1 viral infection and/or
      antiretroviral therapy leading to lipomatosis are acting in a location- and
      adipocyte lineage-dependent manner. 

PMID- 26305326
TI  - Distinct OGT-Binding Sites Promote HCF-1 Cleavage.
AB  - Human HCF-1 (also referred to as HCFC-1) is a transcriptional co-regulator that
      undergoes a complex maturation process involving extensive O-GlcNAcylation and
      site-specific proteolysis. HCF-1 proteolysis results in two active, noncovalently
      associated HCF-1N and HCF-1C subunits that regulate distinct phases of the cell
      division cycle. HCF-1 O-GlcNAcylation and site-specific proteolysis are both
      catalyzed by O-GlcNAc transferase (OGT), which thus displays an unusual dual
      enzymatic activity. OGT cleaves HCF-1 at six highly conserved 26 amino acid
      repeat sequences called HCF-1PRO repeats. Here we characterize the substrate
      requirements for OGT cleavage of HCF-1. We show that the HCF-1PRO-repeat cleavage
      signal possesses particular OGT-binding properties. The glutamate residue at the
      cleavage site that is intimately involved in the cleavage reaction specifically
      inhibits association with OGT and its bound cofactor UDP-GlcNAc. Further, we
      identify a novel OGT-binding sequence nearby the first HCF-1PRO-repeat cleavage
      signal that enhances cleavage. These results demonstrate that distinct OGT
      binding sites in HCF-1 promote proteolysis, and provide novel insights into the
      mechanism of this unusual protease activity. 

PMID- 26305328
TI  - A 3-D Propagation Model for Emerging Land Mobile Radio Cellular Environments.
AB  - A tunable stochastic geometry based Three-Dimensional (3-D) scattering model for
      emerging land mobile radio cellular systems is proposed. Uniformly distributed
      scattering objects are assumed around the Mobile Station (MS) bounded within an
      ellipsoidal shaped Scattering Region (SR) hollowed with an elliptically-cylindric
      scattering free region in immediate vicinity of MS. To ensure the degree of
      expected accuracy, the proposed model is designed to be tunable (as required)
      with nine degrees of freedom, unlike its counterparts in the existing literature.
      The outer and inner boundaries of SR are designed as independently scalable along
      all the axes and rotatable in horizontal plane around their origin centered at
      MS. The elevated Base Station (BS) is considered outside the SR at a certain
      adjustable distance and height w.r.t. position of MS. Closed-form analytical
      expressions for joint and marginal Probability Density Functions (PDFs) of Angle
      of-Arrival (AoA) and Time-of-Arrival (ToA) are derived for both up- and down
      links. The obtained analytical results for angular and temporal statistics of the
      channel are presented along with a thorough analysis. The impact of various
      physical model parameters on angular and temporal characteristics of the channel
      is presented, which reveals the comprehensive insight on the proposed results. To
      evaluate the robustness of the proposed analytical model, a comparison with
      experimental datasets and simulation results is also presented. The obtained
      analytical results for PDF of AoA observed at BS are seen to fit a vast range of
      empirical datasets in the literature taken for various outdoor propagation
      environments. In order to establish the validity of the obtained analytical
      results for spatial and temporal characteristics of the channel, a comparison of
      the proposed analytical results with the simulation results is shown, which
      illustrates a good fit for 10(7) scattering points. Moreover, the proposed model
      is shown to degenerate to various notable geometric models in the literature by
      an appropriate choice of a few parameters.

PMID- 26305327
TI  - Genome-Wide Profiling of PARP1 Reveals an Interplay with Gene Regulatory Regions
      and DNA Methylation.
AB  - Poly (ADP-ribose) polymerase-1 (PARP1) is a nuclear enzyme involved in DNA
      repair, chromatin remodeling and gene expression. PARP1 interactions with
      chromatin architectural multi-protein complexes (i.e. nucleosomes) alter
      chromatin structure resulting in changes in gene expression. Chromatin structure
      impacts gene regulatory processes including transcription, splicing, DNA repair,
      replication and recombination. It is important to delineate whether PARP1
      randomly associates with nucleosomes or is present at specific nucleosome regions
      throughout the cell genome. We performed genome-wide association studies in
      breast cancer cell lines to address these questions. Our studies show that PARP1
      associates with epigenetic regulatory elements genome-wide, such as active
      histone marks, CTCF and DNase hypersensitive sites. Additionally, the binding of
      PARP1 to chromatin genome-wide is mutually exclusive with DNA methylation pattern
      suggesting a functional interplay between PARP1 and DNA methylation. Indeed,
      inhibition of PARylation results in genome-wide changes in DNA methylation
      patterns. Our results suggest that PARP1 controls the fidelity of gene
      transcription and marks actively transcribed gene regions by selectively binding
      to transcriptionally active chromatin. These studies provide a platform for
      developing our understanding of PARP1's role in gene regulation. 

PMID- 26305329
TI  - Time-Course RNA-Seq Analysis Reveals Transcriptional Changes in Rice Plants
      Triggered by Rice stripe virus Infection.
AB  - Rice stripe virus (RSV) has become a major pathogen of rice. To determine how the
      rice transcriptome is modified in response to RSV infection, we used RNA-Seq to
      perform a genome-wide gene expression analysis of a susceptible rice cultivar.
      The transcriptomes of RSV-infected samples were compared to those of mock-treated
      samples at 3, 7, and 15 days post-infection (dpi). From 8 to 11% of the genes
      were differentially expressed (>2-fold difference in expression) in RSV-infected
      vs. noninfected rice. Among them, 532 genes were differentially expressed at all
      three time points. Surprisingly, 37.6% of the 532 genes are related to
      transposons. Gene ontology enrichment analysis revealed that many chloroplast
      genes were down-regulated in infected plants at 3 and 15 dpi. Expression of genes
      associated with cell differentiation and flowering was significantly down
      regulated in infected plants at 15 dpi. In contrast, most of the up-regulated
      genes in infected plants concern the cell wall, plasma membrane, and vacuole and
      are known to function in various metabolic pathways and stress responses. In
      addition, transcripts of diverse transcription factors gradually accumulated in
      infected plants with increasing infection time. We also confirmed that the
      expression of gene subsets (including NBS-LRR domain-containing genes, receptor
      like kinase genes, and genes involving RNA silencing) was changed by RSV
      infection. Taken together, we demonstrated that down-regulation of genes related
      to photosynthesis and flowering was strongly associated with disease symptoms
      caused by RSV and that up-regulation of genes involved in metabolic pathways,
      stress responses, and transcription was related to host defense mechanisms. 

PMID- 26305330
TI  - An Evaluation of the Performance and Economics of Membranes and Separators in
      Single Chamber Microbial Fuel Cells Treating Domestic Wastewater.
AB  - The cost of materials is one of the biggest barriers for wastewater driven
      microbial fuel cells (MFCs). Many studies use expensive materials with idealistic
      wastes. Realistically the choice of an ion selective membrane or nonspecific
      separators must be made in the context of the cost and performance of materials
      available. Fourteen membranes and separators were characterized for durability,
      oxygen diffusion and ionic resistance to enable informed membrane selection for
      reactor tests. Subsequently MFCs were operated in a cost efficient reactor design
      using Nafion, ethylene tetrafluoroethylene (ETFE) or polyvinylidene fluoride
      (PVDF) membranes, a nonspecific separator (Rhinohide), and a no-membrane design
      with a carbon-paper internal gas diffusion cathode. Peak power densities during
      polarisation, from MFCs using no-membrane, Nafion and ETFE, reached 67, 61 and 59
      mWm(-2), and coulombic efficiencies of 68+/-11%, 71+/-12% and 92+/-6%,
      respectively. Under 1000 Omega, Nafion and ETFE achieved an average power density
      of 29 mWm(-2) compared to 24 mWm(-2) for the membrane-less reactors. Over a
      hypothetical lifetime of 10 years the generated energy (1 to 2.5 kWhm(-2)) would
      not be sufficient to offset the costs of any membrane and separator tested.

PMID- 26305331
TI  - Correction: Numerical Methods for the Analysis of Power Transformer Tank
      Deformation and Rupture Due to Internal Arcing Faults.

PMID- 26305332
TI  - Interleukin 21 Controls mRNA and MicroRNA Expression in CD40-Activated Chronic
      Lymphocytic Leukemia Cells.
AB  - Several factors support CLL cell survival in the microenvironment. Under
      different experimental conditions, IL21 can either induce apoptosis or promote
      CLL cell survival. To investigate mechanisms involved in the effects of IL21, we
      studied the ability of IL21 to modulate gene and miRNA expressions in CD40
      activated CLL cells. IL21 was a major regulator of chemokine production in CLL
      cells and it modulated the expression of genes involved in cell movement,
      metabolism, survival and apoptosis. In particular, IL21 down-regulated the
      expression of the chemokine genes CCL4, CCL3, CCL3L1, CCL17, and CCL2, while it
      up-regulated the Th1-related CXCL9 and CXCL10. In addition, IL21 down-regulated
      the expression of genes encoding signaling molecules, such as CD40, DDR1 and
      PIK3CD. IL21 modulated a similar set of genes in CLL and normal B-cells (e.g.
      chemokine genes), whereas other genes, including MYC, TNF, E2F1, EGR2 and GAS-6,
      were regulated only in CLL cells. An integrated analysis of the miRNome and gene
      expression indicated that several miRNAs were under IL21 control and these could,
      in turn, influence the expression of potential target genes. We focused on hsa
      miR-663b predicted to down-regulate several relevant genes. Transfection of hsa
      miR-663b or its specific antagonist showed that this miRNA regulated CCL17, DDR1,
      PIK3CD and CD40 gene expression. Our data indicated that IL21 modulates the
      expression of genes mediating the crosstalk between CLL cells and their
      microenvironment and miRNAs may take part in this process. 

PMID- 26305334
TI  - Influence of Affective Stimuli on Leg Power Output and Associated Neuromuscular
      Parameters during Repeated High Intensity Cycling Exercises.
AB  - The aim of this study was to examine the impact of emotional eliciting pictures
      on neuromuscular performance during repetitive supramaximal cycling exercises
      (RSE). In a randomized order, twelve male participants were asked to perform five
      6-s cycle sprints (interspaced by 24 s of recovery) on a cycle ergometer in front
      of neutral, pleasant or unpleasant pictures. During each RSE, mean power output
      (MPO) and electromyographic activity [root mean square (RMS) and median frequency
      (MF)] of the vastus lateralis and vastus medialis muscles were analyzed.
      Neuromuscular efficiency (NME) was calculated as the ratio of MPO to RMS. Higher
      RMS (232.17 +/- 1.17 vs. 201.90 +/- 0.47 MUV) and MF (68.56 +/- 1.78 vs. 64.18 +/
      2.17 Hz) were obtained in pleasant compared to unpleasant conditions (p < 0.05).
      This emotional effect persisted from the first to the last sprint. Higher MPO was
      obtained in pleasant than in unpleasant conditions (690.65 +/- 38.23 vs. 656.73
      +/- 35.95 W, p < 0.05). However, this emotional effect on MPO was observed only
      for the two first sprints. NME decreased from the third sprint (p < 0.05), which
      indicated the occurrence of peripheral fatigue after the two first sprints. These
      results suggested that, compared with unpleasant pictures, pleasant ones
      increased the neuromuscular performance during RSE. Moreover, the disappearance
      of the beneficial effect of pleasant emotion on mechanical output from the third
      sprint appears to be due to peripheral fatigue. 

PMID- 26305335
TI  - Open Access to a High-Quality, Impartial, Point-of-Care Medical Summary Would
      Save Lives: Why Does It Not Exist?
AB  - James Heilman considers how much good could result from providing clinicians with
      better, freer access to the information they need to do their work. 

PMID- 26305333
TI  - Rac1 Regulates Endometrial Secretory Function to Control Placental Development.
AB  - During placenta development, a succession of complex molecular and cellular
      interactions between the maternal endometrium and the developing embryo ensures
      reproductive success. The precise mechanisms regulating this maternal-fetal
      crosstalk remain unknown. Our study revealed that the expression of Rac1, a
      member of the Rho family of GTPases, is markedly elevated in mouse decidua on
      days 7 and 8 of gestation. To investigate its function in the uterus, we created
      mice bearing a conditional deletion of the Rac1 gene in uterine stromal cells.
      Ablation of Rac1 did not affect the formation of the decidua but led to fetal
      loss in mid gestation accompanied by extensive hemorrhage. To gain insights into
      the molecular pathways affected by the loss of Rac1, we performed gene expression
      profiling which revealed that Rac1 signaling regulates the expression of Rab27b,
      another GTPase that plays a key role in targeting vesicular trafficking.
      Consequently, the Rac1-null decidual cells failed to secrete vascular endothelial
      growth factor A, which is a critical regulator of decidual angiogenesis, and
      insulin-like growth factor binding protein 4, which regulates the bioavailability
      of insulin-like growth factors that promote proliferation and differentiation of
      trophoblast cell lineages in the ectoplacental cone. The lack of secretion of
      these key factors by Rac1-null decidua gave rise to impaired angiogenesis and
      dysregulated proliferation of trophoblast cells, which in turn results in
      overexpansion of the trophoblast giant cell lineage and disorganized placenta
      development. Further experiments revealed that RAC1, the human ortholog of Rac1,
      regulates the secretory activity of human endometrial stromal cells during
      decidualization, supporting the concept that this signaling G protein plays a
      central and conserved role in controlling endometrial secretory function. This
      study provides unique insights into the molecular mechanisms regulating
      endometrial secretions that mediate stromal-endothelial and stromal-trophoblast
      crosstalk critical for placenta development and establishment of pregnancy. 

PMID- 26305336
TI  - Ralstonia solanacearum RSp0194 Encodes a Novel 3-Keto-Acyl Carrier Protein
      Synthase III.
AB  - Fatty acid synthesis (FAS), a primary metabolic pathway, is essential for
      survival of bacteria. Ralstonia solanacearum, a beta-proteobacteria member,
      causes a bacterial wilt affecting more than 200 plant species, including many
      economically important plants. However, thus far, the fatty acid biosynthesis
      pathway of R. solanacearum has not been well studied. In this study, we
      characterized two forms of 3-keto-ACP synthase III, RsFabH and RsFabW, in R.
      solanacearum. RsFabH, the homologue of Escherichia coli FabH, encoded by the
      chromosomal RSc1050 gene, catalyzes the condensation of acetyl-CoA with malonyl
      ACP in the initiation steps of fatty acid biosynthesis in vitro. The RsfabH
      mutant lost de novo fatty acid synthetic ability, and grows in medium containing
      free fatty acids. RsFabW, a homologue of Pseudomonas aeruginosa PA3286, encoded
      by a megaplasmid gene, RSp0194, condenses acyl-CoA (C2-CoA to C10-CoA) with
      malonyl-ACP to produce 3-keto-acyl-ACP in vitro. Although the RsfabW mutant was
      viable, RsfabW was responsible for RsfabH mutant growth on medium containing free
      fatty acids. Our results also showed that RsFabW could condense acyl-ACP (C4-ACP
      to C8-ACP) with malonyl-ACP, to produce 3-keto-acyl-ACP in vitro, which implies
      that RsFabW plays a special role in fatty acid synthesis of R. solanacearum. All
      of these data confirm that R. solanacearum not only utilizes acetyl-CoA, but
      also, utilizes medium-chain acyl-CoAs or acyl-ACPs as primers to initiate fatty
      acid synthesis. 

PMID- 26305337
TI  - Study of Five Pubertal Transition-Related Gene Polymorphisms as Risk Factors for
      Premature Coronary Artery Disease in a Chinese Han Population.
AB  - BACKGROUND: Recently, single nucleotide polymorphisms (SNPs) (DLK-rs10144321,
      SIX6-rs1254337, MKRN3-rs12148769, LIN28B-rs7759938, and KCNK9-rs1469039) were
      found to be strongly associated with age at menarche. Recent studies also
      suggested that age at menarche is a heritable trait and is associated with risks
      for obesity, type 2 diabetes mellitus (T2DM), cardiovascular disease, and all
      cause mortality. Since an association between these five SNPs and premature
      coronary artery disease (CAD) has never been reported, we investigated whether
      these SNPs are associated with premature CAD and its severity in a Chinese Han
      population. METHODS: We enrolled 432 consecutive patients including 198 with
      premature CAD (<55 years in men and <65 years in women) and 234 controls. All
      subjects were genotyped for the five SNPs by the PCR-ligase detection reaction
      method. The associations between these SNPs and premature CAD and its severity
      were analyzed. RESULTS: The following genotypes were identified: GG, AG, and AA
      at rs10144321 and rs12148769; TT, AT, and AA at rs1254337; CC, CT, and TT at
      rs1469039; and TT and CT at rs7759938. Significant differences in genotype
      distribution frequencies at rs1254337 were found between controls and patients
      with premature CAD (P<0.05). No associations were found between the five SNPs and
      the severity of coronary lesions (all P>0.05). Compared with controls, patients
      with premature CAD had a higher prevalence of T2DM and dyslipidemia, and the
      proportion of patients with T2DM rose significantly with an increase in the
      number of stenosed coronary vessels (all P<0.05). After adjustment for the
      clinical parameters in multivariable analysis, three factors were identified that
      significantly increased the risk of premature CAD: the AA genotype at rs1254337
      (OR: 2.388, 95% CI: 1.190-4.792, P = 0.014), male gender (OR: 1.565, 95% CI:
      1.012-2.420, P = 0.044), and T2DM (OR 2.252, 95% CI: 1.233-4.348, P = 0.015).
      CONCLUSIONS: Among the five pubertal transition-related gene polymorphisms, we
      identified an association between rs1254337 and premature CAD in a Chinese Han
      population.

PMID- 26305338
TI  - Phase-locking of bursting neuronal firing to dominant LFP frequency components.
AB  - Neuronal firing in the hippocampal formation relative to the phase of local field
      potentials (LFP) has a key role in memory processing and spatial navigation.
      Firing can be in either tonic or burst mode. Although bursting neurons are common
      in the hippocampal formation, the characteristics of their locking to LFP phase
      are not completely understood. We investigated phase-locking properties of
      bursting neurons using simulations generated by a dual compartmental model of a
      pyramidal neuron adapted to match the bursting activity in the subiculum of a
      rat. The model was driven with stochastic input signals containing a power
      spectral profile consistent with physiologically relevant frequencies observed in
      LFP. The single spikes and spike bursts fired by the model were locked to a
      preferred phase of the predominant frequency band where there was a peak in the
      power of the driving signal. Moreover, the preferred phase of locking shifted
      with increasing burst size, providing evidence that LFP phase can be encoded by
      burst size. We also provide initial support for the model results by analysing
      example data of spontaneous LFP and spiking activity recorded from the subiculum
      of a single urethane-anaesthetised rat. Subicular neurons fired single spikes,
      two-spike bursts and larger bursts that locked to a preferred phase of either
      dominant slow oscillations or theta rhythms within the LFP, according to the
      model prediction. Both power-modulated phase-locking and gradual shift in the
      preferred phase of locking as a function of burst size suggest that neurons can
      use bursts to encode timing information contained in LFP phase into a spike-count
      code. 

PMID- 26305339
TI  - Controlling Nanostructures by Templated Templates: Inheriting Molecular
      Orientation in Binary Heterostructures.
AB  - Precise preparation strategies are required to fabricate molecular nanostructures
      of specific arrangement. In bottom-up approaches, where nanostructures are
      gradually formed by piecing together individual parts to the final structure, the
      self-ordering mechanisms of the involved structures are utilized. In order to
      achieve the desired structures regarding morphology, grain size, and orientation
      of the individual moieties, templates can be applied, which influence the
      formation process of subsequent structures. However, this strategy is of limited
      use for complex architectures because the templates only influence the structure
      formation at the interface between the template and the first compound. Here, we
      discuss the implementation of so-called templated templates and analyze to what
      extent orientations of the initial layers are inherited in the top layers of
      another compound to enable structural control in binary heterostructures. For
      that purpose, we prepared crystalline templates of the organic semiconductors
      pentacene and perfluoropentacene in different exclusive orientations. We observe
      that for templates of both individual materials the molecular orientation is
      inherited in the top layers of the respective counterpart. This behavior is also
      observed for various other molecules, indicating the robustness of this approach.

PMID- 26305340
TI  - Temporal variability in the antiplatelet effects of clopidogrel and aspirin after
      elective drug-eluting stent implantation. An ADAPT-DES substudy.
AB  - Given conflicting data on temporal variability in pharmacodynamic platelet
      responses to clopidogrel, we investigated platelet reactivity on clopidogrel and
      aspirin for up to six months after elective percutaneous coronary intervention
      (PCI) with drug-eluting stents. Platelet reactivity was determined in 102
      patients before loading with clopidogrel and aspirin, and on maintenance therapy
      after PCI on day 1, at one month and six months by VerifyNowTM P2Y12 and Aspirin
      assays and by residual platelet aggregation (RPA) on light transmission
      aggregometry using adenosine diphosphate and arachidonic acid. By VerifyNow
      testing, median (interquartile range) P2Y12 reaction units (PRU) on clopidogrel
      were 166 (90-234), 195 (124-257), and 198 (141-252) on day 1, one month and six
      months after PCI, respectively (p=0.005 day 1 to 1 month, and p=0.86 1 month to 6
      months). Using a cut-off of > 208 PRU, 35 % of patients had high platelet
      reactivity (HPR) to clopidogrel on day 1, 43 % at one month, and 46 % at six
      months after PCI. Between day 1 and six months after PCI, 38.2 % of patients
      changed clopidogrel responder status at least once. Other cut-offs and RPA
      yielded similar results. Platelet inhibition by aspirin was consistent over time
      with only five patients being characterised as having HPR. Considerable variation
      in individual on-clopidogrel platelet reactivity was present during both the
      subacute and the late phases of maintenance therapy after elective PCI. Hence,
      the utility of contemporary platelet function testing to guide antiplatelet
      therapy may be limited. 

PMID- 26305341
TI  - Clinical applicability of robot-guided contact-free laser osteotomy in cranio
      maxillo-facial surgery: in-vitro simulation and in-vivo surgery in minipig
      mandibles.
AB  - Laser was being used in medicine soon after its invention. However, it has been
      possible to excise hard tissue with lasers only recently, and the Er:YAG laser is
      now established in the treatment of damaged teeth. Recently experimental studies
      have investigated its use in bone surgery, where its major advantages are freedom
      of cutting geometry and precision. However, these advantages become apparent only
      when the system is used with robotic guidance. The main challenge is ergonomic
      integration of the laser and the robot, otherwise the surgeon's space in the
      operating theatre is obstructed during the procedure. Here we present our first
      experiences with an integrated, miniaturised laser system guided by a surgical
      robot. An Er:YAG laser source and the corresponding optical system were
      integrated into a composite casing that was mounted on a surgical robotic arm.
      The robot-guided laser system was connected to a computer-assisted preoperative
      planning and intraoperative navigation system, and the laser osteotome was used
      in an operating theatre to create defects of different shapes in the mandibles of
      6 minipigs. Similar defects were created on the opposite side with a
      piezoelectric (PZE) osteotome and a conventional drill guided by a surgeon. The
      performance was analysed from the points of view of the workflow, ergonomics,
      ease of use, and safety features. The integrated robot-guided laser osteotome can
      be ergonomically used in the operating theatre. The computer-assisted and robot
      guided laser osteotome is likely to be suitable for clinical use for ostectomies
      that require considerable accuracy and individual shape. 

PMID- 26305342
TI  - Traumatic superolateral dislocation of the mandibular condyle: case report and
      review.
AB  - We describe what is to our knowledge the first report of a patient who presented
      with a superolateral dislocation of the mandible, in which the medial portion of
      the left condyle was fractured and the lateral fragment was hooked on the
      zygomatic arch without any other associated fracture. 

PMID- 26305343
TI  - BN-Enabled Epitaxy of Pb(1-x)Sn(x)Se Nanoplates on SiO2/Si for High-Performance
      Mid-Infrared Detection.
AB  - By designing a few-layer boron nitried (BN) buffer layer, topological crystalline
      insulator Pb(1-x)Sn(x)Se nanoplates are directly grown on SiO2/Si, which shows
      high compatibility with current Si-based integrated circuit technology. Back
      gated field-effect transistors of Pb(1-x)Sn(x)Se nanoplates exhibit a room
      temperature carrier mobility of 0.73-4.90 cm(2) V(-1) s(-1), comparable to
      layered materials and molecular crystals, and high-efficiency mid-IR detection
      (1.9-2.0 MUm).

PMID- 26305344
TI  - An in situ ATR-IR spectroscopy study of aluminas under aqueous phase reforming
      conditions.
AB  - High temperature/pressure in situ Attenuated Total Reflection Infrared (ATR-IR)
      spectroscopy was used to investigate the phase transformation of support gamma
      Al2O3 into boehmite (AlO(OH)) under the hydrothermal conditions of aqueous phase
      reforming (APR). Activation energy barriers of boehmite formation in hot
      compressed water at temperatures between 150 and 180  degrees C were calculated
      to be 15.9 +/- 4.8 kJ mol(-1) for gamma-Al2O3 and 43.2 +/- 4.3 kJ mol(-1) for
      Pt/gamma-Al2O3. The influence of Pt particles is suggested to slow down the phase
      transformation by selective blockage of the surface nucleation sites. The
      presence of ethylene glycol has also an inhibiting effect on the transformation
      due to the carbon deposits formed on the oxide surface. Post-mortem analysis
      using Raman spectroscopy, (1)H and (27)Al MAS NMR confirms the formation of
      boehmite. 

PMID- 26305345
TI  - [Pruritus ani].
AB  - INTRODUCTION: Pruritus ani is defined as a dermatologic disease characterized by
      itching and/or burning in the perianal area. It occurs in 15% of the population.
      Men are affected more frequently than women, in the ratio 4:1. It is accompanied
      by an irresistible desire to scratch in the perianal area. Pruritus ani is
      divided into two subtypes: primary (idiopathic) and secondary. In idiopathic
      (primary) pruritus it is not possible to detect any other cause of itching.
      Secondary pruritus has an obvious causal origin.The aim of this paper is to offer
      a complex overview of possible causes, diagnostic procedures and treatment
      possibilities of this unpleasant and annoying disease. METHODS: We have
      researched available publications using PubMed and MEDLINE databases, focusing on
      articles on anal pruritus. At first the key word "Pruritus ani" was put in
      without any restrictions. Subsequently, we limited the selection by the time
      period of 5 years and 10 years; then we looked up articles in English, German and
      Czech languages, and finally review articles, clinical trials and others.
      RESULTS: 574 articles were found without entering any restrictions; 45 of them
      were review articles and 25 clinical trials. 437 articles were in the English
      language and 40 of them were review articles. 44 were in the German language and
      1 of them was a review article. A total of 33 articles were found with a 5-year
      time limit. 6 of them were review articles and 4 were clinical trials. 66
      articles from the last 10 years were found. 14 of them were review articles and
      10 were clinical trials. In most of the other articles among the total number of
      articles found, pruritus ani was mentioned only marginally in articles focused on
      different topics. We have not found any summary articles on this topic in Czech
      publications. CONCLUSION: Pruritus ani is a common disease with a number of
      causes; therefore, effective treatment may be insufficient in the initial stages.
      The therapy is focused on the primary cause, if found. Broad differential
      diagnosis options need to be taken into consideration, and reevaluation of the
      therapy is a priority. When no obvious secondary cause is found, the empiric
      treatment is focused on an improvement of hygiene and change in the life style,
      removal of common irritators, and protection of perianal skin.

PMID- 26305346
TI  - [Current status in the treatment of rectal cancer in the Czech Republic regarding
      the rate of complete pathological response after neoadjuvant therapy--PATOD C20
      study 2011-2012].
AB  - INTRODUCTION: Deciding on the strategy in rectal cancer's treatment requires a
      complex and multidisciplinary approach. The primary rectal resection is indicated
      in early stages, while locally advanced tumors should be pretreated by one of the
      modes of neoadjuvant (chemo) radiotherapy. The main goal of this study was to
      explore the therapeutic strategy in patients with rectal cancer in the Czech
      Republic. The second aim was to determine the incidence of the pathological
      complete response after neoadjuvant therapy. METHODS: This is a retrospective
      multicenter clinical study, which includes data from all patients with rectal
      cancer who were treated at participating centers in the period from 01/01/2011 to
      31/12/2012. The required data has been passed into the online registry PATOD
      C20.Three issues have been set up: 1. Characteristics of the center and
      cooperation with the oncological department; 2. Characteristics of the treatment
      of patients with rectal cancer; and 3. Detailed analysis of the group of patients
      with complete pathological response. The analysis was performed with regard to
      the nature of individual departments, i.e. departments of surgery in university
      hospitals with complex oncological centres, departments of surgery within complex
      oncologic centers, and departments of surgery outside complex oncologic centers.
      RESULTS: In total, 21 departments of surgery in the Czech Republic provided data
      about 1860 patients with rectal cancer for the study. The treatment strategy for
      rectal cancer was determined at multidisciplinary seminars at 19 centers (90.5%).
      Statistically significant differences between the centers were found in the
      indication for neoadjuvant treatment (p<0.001), rectal resection with anastomosis
      (p=0.048), and resection without anastomosis (p=0.022). Complete pathological
      response was found in 61 (8.7%) patients. Positivity of mesorectal lymph nodes
      (ypN+) was found in the case of ypT0 stage in 7 (9.7%) patients. CONCLUSION:
      PATOD study showed that therapy of rectal cancer is highly heterogeneous in the
      Czech Republic. Despite the best conditions provided, university hospitals and
      large departments within complex oncologic centers do not fully utilize this
      benefit.

PMID- 26305347
TI  - [SentiMag--the magnetic detection system of sentinel lymph nodes in breast
      cancer].
AB  - INTRODUCTION: The aim of this study was to assess the feasibility of the new
      detection system of sentinel lymph nodes in breast cancer (SentiMag) and to
      compare its use to the standard method of detection with a radioisotope and a
      gamma-probe. METHODS: Twenty breast cancer patients scheduled for sentinel lymph
      node biopsy underwent standard lymphatic mapping with a radioisotope and also
      with the Sienna+ tracer. During the surgery, sentinel lymph nodes were identified
      preferably with the SentiMag system. The gamma-probe was used only at the end of
      the surgery to verify whether all sentinel lymph nodes had been harvested.
      RESULTS: The sentinel lymph node was detected in all cases. Both methods agreed
      in 18 cases, i.e. the lymph node with the highest magnetic value ex vivo was the
      same node as the one with the highest radioactivity. A metastasis in the sentinel
      lymph node was found in three patients. It is very likely that with the sole use
      of the SentiMag system, the results would have been identical to those of using
      the standard method with a radioisotope and the gamma-probe. CONCLUSION: The new
      magnetic detection method of sentinel lymph nodes (SentiMag) is feasible and
      clinically comparable to the gold standard method of detection with a
      radioisotope and the gamma-probe in patients with breast cancer. The new method
      could find its use not only in hospitals where the department of nuclear medicine
      is not available but in all hospitals performing sentinel lymph node biopsies in
      breast cancer and possibly other types of cancer.

PMID- 26305348
TI  - [Acute bleeding into the GI tract--A surgical diagnosis?].
AB  - INTRODUCTION: Patients with signs of acute bleeding into the gastrointestinal
      tract are hospitalized at intensive care units of surgical departments for
      organizational reasons. There is a growing proportion of those treated with
      various forms of antithrombotic therapy. From the onset of endoscopic methods of
      haemostasis, mortality is low and surgical treatment of these patients is rarely
      required. Their treatment takes up a lot of human and financial resources. The
      question remains, whether it would be possible to stop the volume growth or even
      reduce the number of these patients. METHODS: A retrospective analysis of
      patients hospitalized for acute gastrointestinal bleeding at our department
      focused on the use of various forms of antithrombotic therapy as a risk factor.
      RESULTS: A total of 251 patients were hospitalized with acute bleeding into the
      digestive tract during 24 months at our department. 107 of these were receiving
      antiplatelet, anticoagulant or combination therapy. None of the patients used any
      form of gastroprotection. CONCLUSION: The number of patients acutely bleeding
      into the digestive tract is high and rising particularly within the group using
      various forms of antithrombotic therapy. Despite the existence of accepted
      guidelines, these patients are often not equipped with any form of
      gastroprotection. Compliance with the accepted standards could positively
      influence this unfavourable trend.

PMID- 26305349
TI  - Critical complications of intestinal tuberculosis--a case report.
AB  - Intestinal tuberculosis is a rare disease in developed countries, affecting
      mainly immigrants and immunocompromised patients. Clinical presentation may mimic
      many other abdominal diseases such as intra-abdominal infections, tumors, and
      Crohn's disease. Differential diagnosis of Crohn's disease and intestinal
      tuberculosis poses a dilemma to clinicians and pathologists as both are chronic
      granulomatous disorders with similar clinical features. We report the case of a
      53 year-old man presenting with perforated intestinal tuberculosis in which the
      initial diagnostic work-up suggested Crohn's disease. The severity of the
      findings resulted in critical complications during the course of treatment. This
      case points out the need for awareness of intestinal tuberculosis in the
      differential diagnosis of chronic intestinal disease.

PMID- 26305350
TI  - [Endoscopic endonasal treatment of cerebrospinal fluid leak caused by clival
      fracture--a case report].
AB  - INTRODUCTION: Clivus is a central structure of the skull base located in the
      vicinity of the brainstem and vital brain vessels. Clival fractures are usually
      caused by a high-energy trauma. Cerebrospinal fluid leak is one of the most
      common complications. CASE REPORT: A middle-aged male sustained a mild head
      trauma, followed by a nasal cerebrospinal fluid leak. CT scan revealed the
      massive pneumocephalus and the fracture of the clivus in the posterior wall of
      the sphenoidal sinus. We performed an endoscopic endonasal surgery to seal the
      defect. DISCUSSION: Pneumatization of a sphenoidal sinus shows high variability.
      In the presented case, extreme pneumatization of the sinuses was combined with
      the gracile clivus, which was the predisposing factor for fracture. Traumatic
      cerebrospinal fluid leak carries the risk of intracranial hypotension and
      meningitis. Microscopic transseptal management is the classical surgical
      approach, while endoscopy provides the modern miniinvasive option. CONCLUSION:
      Endoscopic endonasal treatment of traumatic cerebrospinal fluid leak is the
      treatment of choice for the clival fractures.

PMID- 26305351
TI  - [Heterotopic mesenteric ossification].
AB  - Heterotopic mesenteric ossification (HMO) is a rare disease inducing pathological
      bone tissue formation in the abdominal cavity after multiple operational traumas.
      The authors present an unusual case of mesenteric ossification formation in a 30
      year-old man after surgery due to status ileosus on the basis of intestinal
      incarceration. After being released into home treatment the patient had to be
      hospitalized again and reoperated. During the next six weeks, the patient was
      reoperated three more times due to intestinal status ileosus and significant
      leaking of the entero-cutaneous fistula. Despite intensive parenteral
      hyperalimentation the patients condition did not improve and metabolic breakdown
      became fatal for the patient. Pathophysiology of the mechanism of bone tissue
      formation in soft tissues is unknown.

PMID- 26305352
TI  - An occlusion paradigm to assess the importance of the timing of the quiet eye
      fixation.
AB  - The aim of the study was to explore the significance of the 'timing' of the quiet
      eye (QE), and the relative importance of late (online control) or early (pre
      programming) visual information for accuracy. Twenty-seven skilled golfers
      completed a putting task using an occlusion paradigm with three conditions: early
      (prior to backswing), late (during putter stroke), and no (control) occlusion of
      vision. Performance, QE, and kinematic variables relating to the swing were
      measured. Results revealed that providing only early visual information
      (occluding late visual information) had a significant detrimental effect on
      performance and kinematic measures, compared to the control condition (no
      occlusion), despite QE durations being maintained. Conversely, providing only
      late visual information (occluding early visual information) was not
      significantly detrimental to performance or kinematics, with results similar to
      those in the control condition. These findings imply that the visual information
      extracted during movement execution - the late proportion of the QE - is critical
      when golf putting. The results challenge the predominant view that the QE serves
      only a pre-programming function. We propose that the different proportions of the
      QE (before and during movement) may serve different functions in supporting
      accuracy in golf putting.

PMID- 26305353
TI  - Effects of Relaxing Music on Mental Fatigue Induced by a Continuous Performance
      Task: Behavioral and ERPs Evidence.
AB  - The purpose of this study was to investigate whether listening to relaxing music
      would help reduce mental fatigue and to maintain performance after a continuous
      performance task. The experiment involved two fatigue evaluation phases carried
      out before and after a fatigue inducing phase. A 1-hour AX-continuous performance
      test was used to induce mental fatigue in the fatigue-inducing phase, and
      participants' subjective evaluation on the mental fatigue, as well as their
      neurobehavioral performance in a Go/NoGo task, were measured before and after the
      fatigue-inducing phase. A total of 36 undergraduate students (18-22 years)
      participated in the study and were randomly assigned to the music group and
      control group. The music group performed the fatigue-inducing task while
      listening to relaxing music, and the control group performed the same task
      without any music. Our results revealed that after the fatigue-inducing phase,
      (a) the music group demonstrated significantly less mental fatigue than control
      group, (b) reaction time significantly increased for the control group but not
      for the music group, (c) larger Go-P3 and NoGo-P3 amplitudes were observed in the
      music group, although larger NoGo-N2 amplitudes were detected for both groups.
      These results combined to suggest that listening to relaxing music alleviated the
      mental fatigue associated with performing an enduring cognitive-motor task. 

PMID- 26305354
TI  - Warmer and Wetter Soil Stimulates Assimilation More than Respiration in Rainfed
      Agricultural Ecosystem on the China Loess Plateau: The Role of Partial Plastic
      Film Mulching Tillage.
AB  - Effects of agricultural practices on ecosystem carbon storage have acquired
      widespread concern due to its alleviation of rising atmospheric CO2
      concentrations. Recently, combining of furrow-ridge with plastic film mulching in
      spring maize ecosystem was widely applied to boost crop water productivity in the
      semiarid regions of China. However, there is still limited information about the
      potentials for increased ecosystem carbon storage of this tillage method. The
      objective of this study was to quantify and contrast net carbon dioxide exchange,
      biomass accumulation and carbon budgets of maize (Zea maize L.) fields under the
      traditional non-mulching with flat tillage (CK) and partial plastic film mulching
      with furrow-ridge tillage (MFR) on the China Loess Plateau. Half-hourly net
      ecosystem CO2 exchange (NEE) of both treatments were synchronously measured with
      two eddy covariance systems during the growing seasons of 2011 through 2013. At
      same time green leaf area index (GLAI) and biomass were also measured biweekly.
      Compared with CK, the warmer and wetter (+1.3 degrees C and +4.3%) top soil at
      MFR accelerated the rates of biomass accumulation, promoted greater green leaf
      area and thus shortened the growing seasons by an average value of 10.4 days for
      three years. MFR stimulated assimilation more than respiration during whole
      growing season, resulting in a higher carbon sequestration in terms of NEE of -79
      gC/m2 than CK. However, after considering carbon in harvested grain (or
      aboveground biomass), there is a slight higher carbon sink (or a stronger carbon
      source) in MFR due to its greater difference of aboveground biomass than that of
      grain between both treatments. These results demonstrate that partial plastic
      film mulched furrow-ridge tillage with aboveground biomass exclusive of grain
      returned to the soil is an effective way to enhance simultaneously carbon
      sequestration and grain yield of maize in the semiarid regions. 

PMID- 26305355
TI  - Structural Analysis of the Rubisco-Assembly Chaperone RbcX-II from Chlamydomonas
      reinhardtii.
AB  - The most prevalent form of the Rubisco enzyme is a complex of eight catalytic
      large subunits (RbcL) and eight regulatory small subunits (RbcS). Rubisco
      biogenesis depends on the assistance by specific molecular chaperones. The
      assembly chaperone RbcX stabilizes the RbcL subunits after folding by chaperonin
      and mediates their assembly to the RbcL8 core complex, from which RbcX is
      displaced by RbcS to form active holoenzyme. Two isoforms of RbcX are found in
      eukaryotes, RbcX-I, which is more closely related to cyanobacterial RbcX, and the
      more distant RbcX-II. The green algae Chlamydomonas reinhardtii contains only
      RbcX-II isoforms, CrRbcX-IIa and CrRbcX-IIb. Here we solved the crystal structure
      of CrRbcX-IIa and show that it forms an arc-shaped dimer with a central
      hydrophobic cleft for binding the C-terminal sequence of RbcL. Like other RbcX
      proteins, CrRbcX-IIa supports the assembly of cyanobacterial Rubisco in vitro,
      albeit with reduced activity relative to cyanobacterial RbcX-I. Structural
      analysis of a fusion protein of CrRbcX-IIa and the C-terminal peptide of RbcL
      suggests that the peptide binding mode of RbcX-II may differ from that of
      cyanobacterial RbcX. RbcX homologs appear to have adapted to their cognate
      Rubisco clients as a result of co-evolution. 

PMID- 26305356
TI  - Evaluation of Tangential Flow Filtration for the Concentration and Separation of
      Bacteria and Viruses in Contrasting Marine Environments.
AB  - Tangential flow filtration (TFF), which has been widely adopted to concentrate a
      diverse array of microbes from water, is a promising method of microbial
      separation or removal. However, it is essential to select an optimal membrane
      suitable for the specific filtration application. This study evaluated two
      different scales of TFF systems for concentrating and separating microbes
      (including bacteria and viruses) from contrasting marine waters. Among bacteria
      size membranes, polyvinylidene difluoride (PVDF) membranes showed higher
      bacterial recovery, but lower viral permeation efficiencies than polyethersulfone
      (PES) membranes, regardless of environments and scales of TFF. Estuary samples
      showed significantly higher percentages of bacterial retention than nearshore and
      ocean samples. For virus-size membranes, a higher viral recovery and lower
      sorption was observed for regenerated cellulose membrane than PES membranes in
      the small-scale TFF. Similar viral recoveries were observed between PES membranes
      in the large-scale TFF, with higher viral concentrations being observed in
      estuary samples than in nearshore samples. Deep ocean samples showed the lowest
      recovery of viruses, which was consistent with observations of bacterial
      recovery. Synthetically, PVDF may be more suitable for the concentration of
      bacterial cells, while PES would be a better choice for the collection of
      viruses. When compared with the PES membrane, regenerated cellulose is better for
      viral concentration, while PES is recommended to obtain bacteria- and virus-free
      seawater. 

PMID- 26305357
TI  - Robot-assisted partial nephrectomy in cystic tumours: analysis of the Vattikuti
      Global Quality Initiative in Robotic Urologic Surgery (GQI-RUS) database.
AB  - OBJECTIVE: To evaluate the outcomes of robot-assisted partial nephrectomy (RAPN)
      in cystic tumours, analysing a large, multi-institutional, retrospective series
      of RAPN, as limited data are available about the outcome of RAPN in cystic
      tumours. PATIENTS AND METHODS: We evaluated 465 patients who received RAPN for
      either cystic or solid tumours from 2010 to 2013 and included in the multi
      institutional, retrospective Vattikuti Global Quality Initiative in Robotic
      Urologic Surgery (GQI-RUS) database. Univariable and multivariable linear and
      logistic regression models addressed the association of cystic tumours with
      perioperative outcomes. RESULTS: In all, 54 (12%) tumours were cystic. Cystic
      tumours were associated with significantly lower operative time (t -3.9; P <
      0.001), once adjusted for the effect of covariates, whereas blood loss and warm
      ischaemia time were similar. Postoperative any grade complications were recorded
      in 66 solid (16%) and nine cystic (17%) tumours (P = 0.08). In multivariable
      analysis, cystic tumours were not associated with a significantly lower risk of
      any grade postoperative complications [odds ratio (OR) 0.9; P = 0.8]. Similarly,
      presence of tumours with cystic features was not associated with a significantly
      different risk of high-grade postoperative complications (OR 2.2; P = 0.1).
      Prevalence of cancer histology and positive surgical margin rates were similar in
      cystic and solid tumours. Cystic tumours were not associated with significantly
      different postoperative estimated glomerular filtration rate (t 0.4; P = 0.7),
      once adjusted for the effect of covariates. CONCLUSIONS: RAPN can be performed in
      cystic renal tumours with perioperative, pathological, and functional outcomes
      similar to those achievable in solid tumours.

PMID- 26305358
TI  - Correction: Smoking, Smoking Cessation, and the Risk of Type 2 Diabetes among
      Japanese Adults: Japan Epidemiology Collaboration on Occupational Health Study.

PMID- 26305359
TI  - Risk of Shingles in Adults with Primary Sjogren's Syndrome and Treatments: A
      Nationwide Population-Based Cohort Study.
AB  - BACKGROUND: Primary Sjogren's syndrome (pSS) is associated with immunological
      dysfunctions--a well-known risk factor of shingles. This study aimed to examine
      the incidence and risk of shingles in adults with pSS and pharmacological
      treatments. METHODS: This retrospective population-based cohort study was
      conducted using National Health Insurance claims data. Using propensity scores,
      4,287 pSS adult patients and 25,722-matched cohorts by age, gender, selected
      comorbidities and Charlson comorbidity index scores were identified. Kaplan-Meier
      analysis and Cox regression were conducted to compare the differences in
      developing shingles. In pSS, oral and eye dryness are treated with substitute
      agents. Extraglandular features are often treated with pharmacological drugs
      including steroids and immunosuppressants. pSS patients were grouped as follows:
      no pharmacological drugs, steroids alone; immunosuppressants alone; combined
      therapies. RESULTS: During the follow-up, 463 adults with pSS (10.80%) and 1,345
      control cohorts (5.23%) developed shingles. The cumulative incidence of shingles
      in pSS patients (18.74/1,000 patient-years) was significantly higher than
      controls (8.55/1,000 patient-years). The adjusted hazard ratio (HR) of shingles
      was 1.69 (95% confidence interval (CI) 1.50-1.90). In age-subgroup analyses,
      incidences of shingles in pSS increased with age and peaked in pSS patients aged
      ?60; however, adjusted HRs decreased with age. Compared to control cohorts with
      no drugs, adjusted HRs for shingles in pSS patients were ranked from high to low
      as: combined therapies (4.14; 95% CI 3.14-5.45) > immunosuppressants alone (3.24;
      95% CI 2.36-4.45) > steroids alone (2.54; 95% CI 2.16-2.97) > no pharmacological
      drugs (2.06; 95% CI 1.76-2.41). Rates of shingles-associated hospitalization and
      postherpetic neuralgia were 5.62% and 24.41%, both of which were significantly
      higher than those (2.60%; 13.01%) in the control cohorts. CONCLUSIONS: Adults
      with pSS were at greater risk for shingles than control cohorts. Drug exposures
      significantly increased the risk of shingles in pSS.

PMID- 26305360
TI  - The Homeodomain Iroquois Proteins Control Cell Cycle Progression and Regulate the
      Size of Developmental Fields.
AB  - During development, proper differentiation and final organ size rely on the
      control of territorial specification and cell proliferation. Although many
      regulators of these processes have been identified, how both are coordinated
      remains largely unknown. The homeodomain Iroquois/Irx proteins play a key,
      evolutionarily conserved, role in territorial specification. Here we show that in
      the imaginal discs, reduced function of Iroquois genes promotes cell
      proliferation by accelerating the G1 to S transition. Conversely, their increased
      expression causes cell-cycle arrest, down-regulating the activity of the Cyclin
      E/Cdk2 complex. We demonstrate that physical interaction of the Iroquois protein
      Caupolican with Cyclin E-containing protein complexes, through its IRO box and
      Cyclin-binding domains, underlies its activity in cell-cycle control. Thus,
      Drosophila Iroquois proteins are able to regulate cell-autonomously the growth of
      the territories they specify. Moreover, our results provide a molecular mechanism
      for a role of Iroquois/Irx genes as tumour suppressors. 

PMID- 26305361
TI  - Soil-Transmitted Helminths and Associated Factors among Pre-School Children in
      Butajira Town, South-Central Ethiopia: A Community-Based Cross-Sectional Study.
AB  - BACKGROUND: Soil-transmitted helminths (STH) remain a major public health
      problem, particularly in tropical and sub-tropical regions of the world. Though
      infections are prevalent among all age groups, the world health organization
      (WHO) considers Pre-school age children (PSAC), school-aged children, and
      pregnant women as segments of population at high risk of STH morbidities.
      OBJECTIVE: This study aimed at determining the prevalence and infection intensity
      of STH and associated factors among PSAC in Butajira Town, south-central
      Ethiopia. METHODS: A community-based cross-sectional study was conducted from May
      to June, 2014 in Butajira Town. The PSAC were selected by systematic sampling
      technique and invited to participate in the present study. McMaster technique was
      employed for parasitological analysis of stool samples. Pearson's Chi-square and
      Fisher's exact tests were performed where appropriate to identify any association
      between STH infection and independent factors. Multivariate logistic regression
      model was fitted to identify independent predictors of STH among the PSAC. P
      value less than 0.05 was considered statistically significant. RESULTS: A total
      of 377 (with 96% compliance rate) PSAC were able to provide complete data (socio
      demographic information and stool sample). The study showed that 23.3% (88/377)
      PSAC were infected with one or more species of STH. Ascaris lumbricoides was the
      most prevalent STH (14.9%) followed by Trichuris trichiura (6.4%). The overall
      infection intensity, expressed as geometric mean for A. lumbricoides, T.
      trichiura, and hookworms were 229, 178, and 154 eggs per gram of stool,
      respectively. The multivariate logistic regression model estimated that being in
      the age group of 36-47 months (AOR: 2.5, 95% CI: 1.2-5.3, P = 0.016), untrimmed
      finger nail (AOR: 3.2, 95% CI: 1.8-5.5, P < 0.001), and not washing hands before
      a meal (AOR: 3.0, 95% CI: 1.7-5.4, P < 0.001) were independent predictors of STH
      infections among the children. CONCLUSION: The present study showed that STH was
      a public health problem among PSAC in the study area necessitating annual
      deworming to control morbidities associated with STH. Besides, the existing
      health education program should also be strengthened to prevent re-infection.

PMID- 26305362
TI  - Point-of-Care Information in Open Access: A Time to Sow?
AB  - The PLOS Medicine Editors support expanding the global benefits of clinical point
      of-care information through open access and note challenges that may arise along
      the way. 

PMID- 26305363
TI  - Reliability and Validity of the Chinese Version Appropriateness Evaluation
      Protocol.
AB  - OBJECTIVE: To adapt the Appropriateness Evaluation Protocol (AEP) to the specific
      settings of health care in China and to validate the Chinese version AEP (C-AEP).
      METHODS: Forward and backward translations were carried out to the original
      criteria. Twenty experts participated in the consultancy to form a preliminary
      version of the C-AEP. To ensure applicability, tests of reliability and validity
      were performed on 350 admissions and 3,226 hospital days of acute myocardial
      infraction patients and total hip replacement patients in two tertiary hospitals
      by two C-AEP reviewers and two physician reviewers. Overall agreement, specific
      agreement, and Cohen's Kappa were calculated to compare the concordance of
      decisions between pairs of reviewers to test inter-rater reliability and
      convergent validity. The use of "overrides" and opinions of experts were recorded
      as measurements of content validity. Face validity was tested through collecting
      perspectives of nonprofessionals. Sensitivity, specificity, and predictive values
      were also reported. RESULTS: There are 14 admission and 24 days of care criteria
      in the initial version of C-AEP. Kappa coefficients indicate substantial
      agreement between reviewers: with regard to inter-rater reliability, Kappa
      (kappa) coefficients are 0.746 (95% confidence interval [CI] 0.644-0.834) and
      0.743 (95% CI 0.698-0.767) of admission and hospital days, respectively; for
      convergent validity, the kappa statistics are 0.678 (95% CI 0.567-0.778) and
      0.691 (95% CI 0.644-0.717), respectively. Overrides account for less than 2% of
      all judgments. Content validity and face validity were confirmed by experts and
      nonprofessionals, respectively. According to the C-AEP reviewers, 18.3% of
      admissions and 28.5% of inpatient days were deemed inappropriate. CONCLUSIONS:
      The C-AEP is a reliable and valid screening tool in China's tertiary hospitals.
      The prevalence of inappropriateness is substantial in our research. To reduce
      inappropriate utilization, further investigation is needed to elucidate the
      reasons and risk factors for this inappropriateness.

PMID- 26305364
TI  - Balloon aortic valvuloplasty--ups and downs--are we facing a procedure comeback?
AB  - BACKGROUND: Recently, there has been renewed interest in balloon aortic
      valvuloplasty (BAV). AIM: To analyse the indications and short-term outcome of
      BAV since transcatheter aortic valve implantation (TAVI) was launched in our
      institution. METHODS: Between September 2010 and September 2014, 25 consecutive
      patients (19 female, 6 male) underwent BAV. The mean age was 72 +/- 11.4 years,
      mean EuroScore II was 10.4 +/- 11.7%, mean logistic EuroScore 23.5 +/- 23.6%,
      mean Society of Thoracic Surgeons mortality risk score was 21.8 +/- 13.6%. The
      indications for BAV were: advanced haemodynamically unstable heart failure (HF)
      including cardiogenic shock or pulmonary oedema (n = 7), co-morbidities requiring
      urgent non-cardiac surgery (n = 8), palliative treatment (n = 6), and an
      intention to bridge to TAVI or aortic valve replacement in patients with severe
      HF (n = 4). RESULTS: In-hospital mortality was 20% (n = 5) and occurred in
      patients who underwent BAV in the setting of haemodynamically unstable HF. Other
      major complications included pacemaker implantation (n = 2), major vascular
      complications (n = 4), and cardiac tamponade (n = 1). There were no patients who
      required conversion to cardiac surgery. The mean peak aortic transvalvular
      gradient decreased from 96.9 +/- 29.5 to 60.3 +/- 15.5 mm Hg (p = 0.0001) after
      BAV. We did not observe significant aortic regurgitation. CONCLUSIONS: Treatment
      of advanced and haemodynamically unstable aortic stenosis, bridge to non-cardiac
      surgery and palliative therapy are the main reasons for BAV in recent years. BAV
      as a bridge to TAVI or aortic valve replacement may be an option for some
      patients. Short-term results are good with relatively low mortality and morbidity
      related to the procedure. Mortality in haemodynamically unstable patients
      presenting with cardiogenic shock or pulmonary oedema treated with BAV is very
      high.

PMID- 26305365
TI  - The influence of cavotricuspid isthmus length on total radiofrequency energy to
      cure right atrial flutter.
AB  - BACKGROUND AND AIM: The complexity and success rate of right atrial flutter
      ablation is highly dependent on anatomical structures. METHODS: The study
      comprised 35 consecutive patients (33-77 years old; 30 men) who underwent
      ablation of typical atrial flutter. The linear ablation line was measured offline
      as a surrogate for the cavotricuspid isthmus (CTI) length with the help of a
      three-dimensional mapping and navigation system (EnsiteTM). Biophysical
      parameters, such as total radiofrequency (RF) energy and time of the ablation
      procedure, were analysed to test the hypothesis that any of these variables show
      a correlation with the length of the ablation line. RESULTS: Bidirectional
      isthmus block was achieved in all cases. The isthmus length had a mean value of
      32 +/- 12 mm with a range of 14-57 mm. The linear regression between the CTI
      length and the total RF energy was not significant. There was no significant
      difference in energy (32.281 +/- 25.587 vs. 37.136 +/- 24.250 W-s, p = NS) or in
      the total ablation time (759 +/- 646 vs. 802 +/- 533 s, p = NS) between the group
      with short (< 29 mm; n = 17) vs. long CTI (>= 29 mm, n = 18). When comparing
      different ablation technologies, total RF energy delivered with 8-mm catheter
      technology (group I) was significantly lower than in patients with cross over
      from 8-mm to cooled ablation technology (group III) (29.615 +/- 12.331 vs. 62.674
      +/- 28.735 W-s, p = 0.01). The same was true for the comparison between cooled
      ablation technology (group II) and group III (19.879 +/- 13.669 vs. 62.674 +/-
      28.735 W-s, p = 0.002). CONCLUSIONS: The length of the CTI as measured with help
      of a three-dimensional mapping system may reflect only a weak indicator for the
      complexity of flutter ablation procedures. The thickness of musculature and
      specific anatomy of the CTI seem to be the main challenges in performing a linear
      ablation to achieve bidirectional block.

PMID- 26305366
TI  - Quality of life in patients with paroxysmal atrial fibrillation after
      circumferential pulmonary vein ablation.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia and is
      associated with a deterioration of quality of life (QoL). Catheter ablation is a
      therapeutic strategy for some patients with AF. The effectiveness of pulmonary
      vein isolation is still under assessment. AIM: To assess the long-term influence
      of circumferential pulmonary vein ablation (CPVA) on QoL in patients with AF.
      METHODS: The study population consisted of 33 patients (26 males, age 54.2 +/- 9
      years) with highly symptomatic (EHRA II-III) drug refractory paroxysmal AF, who
      underwent CPVA. A clinical examination, electrocardiogram (ECG), and Holter ECG
      were performed before and during a one-year follow-up. The SF-36 Medical Outcomes
      Survey Short-Form QoL questionnaire, scored on a 0-100 scale for each of eight
      domains: bodily pain (BP), general health (GH), mental health (MH), physical
      functioning (PF), role-emotional (RE), role-physical (RP), social functioning
      (SF), and vitality (V), was collected before and one year after CPVA. RESULTS: In
      the one-year follow-up 27 (82%) patients were free of AF. EHRA symptoms were
      improved one-year after CPVA regardless of CPVA efficacy. After the follow-up the
      SF-36 questionnaire results improved significantly in all of the subscales in
      patients without a recurrence of AF after CPVA. In subjects with a recurrence of
      AF, all of the subscales did not indicate any statistically significant
      differences. There was an association between the CPVA and the following QoL
      domains: GH (p = 0.018), PF (p = 0.042), and V (p = 0.041). The highest values of
      the GH and V domains were found in the non-recurrence patients one year after
      CPVA. CONCLUSIONS: CPVA results in the clinical improvement of patients with
      symptomatic AF regardless of the final arrhythmia termination. Patients after
      successful CPVA experienced a significant improvement in all of the subscales of
      the QoL.

PMID- 26305367
TI  - Comparison of mid-term results of transcatheter aortic valve implantation in high
      risk patients with logistic EuroSCORE >= 20% or < 20.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) is an established
      treatment method in selected high-risk patients with severe aortic stenosis.
      However, data on which patients gain most benefit from this procedure is still
      limited. According to the European consensus document, TAVI is recommended for
      high-risk patients with logistic EuroSCORE (log ES) >= 20%. To date, little is
      known about TAVI outcomes in patients with log ES < 20%. AIM: To evaluate
      outcomes of TAVI in high-risk patients with log ES >= 20% in comparison with high
      risk patients with log ES < 20%. METHODS AND RESULTS: Of 93 patients who
      underwent TAVI at our institution between January 2009 and December 2011, we
      identified 59 (63.4%) patients with log ES >= 20% (Group 1) and 34 (36.6%)
      patients with log ES < 20% (Group 2). The mean log ES was 30.9 +/- 9.7% in Group
      1 and 12.7 +/- 4.9% in Group 2 (p < 0.01). Significant differences were found
      between the two groups in regard to age (82.9 +/- 5.9 vs. 78.7 +/- 7.8 years, p =
      0.001), left ventricular ejection fraction (51.5 +/- 14% vs. 60.4 +/- 9.6%, p =
      0.002), pulmonary artery systolic pressure (56 +/- 11 vs. 49 +/- 10.6 mm Hg, p =
      0.02), and glomerular filtration rate (51.3 +/- 18.4 vs. 60.6 +/- 16.6 mL/min/m2,
      p = 0.02). Survival rates at 1 and 2 years were 76.6% and 69.0% in Group 1 and
      89.0% and 83.6% in Group 2 (p = NS). However, cardiovascular mortality at 1 and 2
      years was higher in Group 1 compared to Group 2 (21.4% and 28.6% vs. 8.1% and
      10.8% in Groups 1 and 2, respectively). CONCLUSIONS: The results of this study
      demonstrate that at 2 years of follow-up, TAVI in high-risk patients with log ES
      >= 20% was associated with a higher cardiovascular mortality compared to high
      risk patients with log ES < 20%.

PMID- 26305368
TI  - Cyanobacterial KnowledgeBase (CKB), a Compendium of Cyanobacterial Genomes and
      Proteomes.
AB  - Cyanobacterial KnowledgeBase (CKB) is a free access database that contains the
      genomic and proteomic information of 74 fully sequenced cyanobacterial genomes
      belonging to seven orders. The database also contains tools for sequence
      analysis. The Species report and the gene report provide details about each
      species and gene (including sequence features and gene ontology annotations)
      respectively. The database also includes cyanoBLAST, an advanced tool that
      facilitates comparative analysis, among cyanobacterial genomes and genomes of E.
      coli (prokaryote) and Arabidopsis (eukaryote). The database is developed and
      maintained by the Sub-Distributed Informatics Centre (sponsored by the Department
      of Biotechnology, Govt. of India) of the National Facility for Marine
      Cyanobacteria, a facility dedicated to marine cyanobacterial research. CKB is
      freely available at http://nfmc.res.in/ckb/index.html. 

PMID- 26305370
TI  - Atomic Layer Deposition of Silicon Nitride from Bis(tert-butylamino)silane and N2
      Plasma.
AB  - Atomic layer deposition (ALD) of silicon nitride (SiNx) is deemed essential for a
      variety of applications in nanoelectronics, such as gate spacer layers in
      transistors. In this work an ALD process using bis(tert-butylamino)silane (BTBAS)
      and N2 plasma was developed and studied. The process exhibited a wide temperature
      window starting from room temperature up to 500  degrees C. The material
      properties and wet-etch rates were investigated as a function of plasma exposure
      time, plasma pressure, and substrate table temperature. Table temperatures of 300
      500  degrees C yielded a high material quality and a composition close to Si3N4
      was obtained at 500  degrees C (N/Si=1.4+/-0.1, mass density=2.9+/-0.1 g/cm3,
      refractive index=1.96+/-0.03). Low wet-etch rates of ~1 nm/min were obtained for
      films deposited at table temperatures of 400  degrees C and higher, similar to
      that achieved in the literature using low-pressure chemical vapor deposition of
      SiNx at >700  degrees C. For novel applications requiring significantly lower
      temperatures, the temperature window from room temperature to 200  degrees C can
      be a solution, where relatively high material quality was obtained when operating
      at low plasma pressures or long plasma exposure times.

PMID- 26305369
TI  - Early Events in the Amyloid Formation of the A546T Mutant of Transforming Growth
      Factor beta-Induced Protein in Corneal Dystrophies Compared to the
      Nonfibrillating R555W and R555Q Mutants.
AB  - The human transforming growth factor beta-induced protein (TGFBIp) is involved in
      several types of corneal dystrophies where protein aggregation and amyloid fibril
      formation severely impair vision. Most disease-causing mutations are located in
      the last of four homologous fasciclin-1 (FAS1) domains of the protein, and it has
      been shown that when isolated, the fourth FAS1 domain (FAS1-4) mimics the
      behavior of full-length TGFBIp. In this study, we use molecular dynamics
      simulations and principal component analysis to study the wild-type FAS1-4 domain
      along with three disease-causing mutations (R555W, R555Q, and A546T) to decipher
      any internal difference in dynamical properties of the domains that may explain
      their varied stabilities and aggregation properties. In addition, we use a
      protein-protein docking method in combination with chemical cross-linking
      experiments and mass spectrometry of the cross-linked species to obtain
      information about interaction faces between identical FAS1-4 domains. The results
      show that the pathogenic mutations A546T and R555W affect the packing in the
      hydrophobic core of FAS1-4 in different directions. We further show that the FAS1
      4 monomers associate using their beta-rich regions, consistent with peptides
      observed to be part of the amyloid fibril core in lattice corneal dystrophy
      patients. 

PMID- 26305371
TI  - Low Cardiorespiratory Fitness is Partially Linked to Ventilatory Factors in Obese
      Adolescents.
AB  - AIM: To examine the role of ventilatory constraint on cardiorespiratory fitness
      in obese adolescents. METHODS: Thirty obese adolescents performed a maximal
      incremental cycling exercise and were divided into 2 groups based on maximal
      oxygen uptake (VO2peak): those presenting low (L; n = 15; VO2peak: 72.9 +/- 8.6%
      predicted) or normal (N; n = 15; VO2peak: 113.6 +/- 19.2% predicted)
      cardiorespiratory fitness. Both were compared with a group of healthy controls
      (C; n = 20; VO2peak: 103.1 +/- 11.2% predicted). Ventilatory responses were
      explored using the flow volume loop method. RESULTS: Cardiorespiratory fitness
      (VO2peak, in % predicted) was lower in L compared with C and N and was moderately
      associated with the percent predicted forced vital capacity (FVC) (r = .52; p <
      .05) in L. At peak exercise, end inspiratory point was lower in L compared with N
      and C (77.4 +/- 8.1, 86.4 +/- 7.7, and 89.9 +/- 7.6% FVC in L, N, and C,
      respectively; p < .05), suggesting an increased risk of ventilatory constraint in
      L, although at peak exercise this difference could be attributed to the lower
      maximal ventilation in L. CONCLUSION: Forced vital capacity and ventilatory
      strategy to incremental exercise slightly differed between N and L. These results
      suggest a modest participation of ventilatory factors to exercise intolerance.

PMID- 26305372
TI  - SERPINE2 Inhibits IL-1alpha-Induced MMP-13 Expression in Human Chondrocytes:
      Involvement of ERK/NF-kappaB/AP-1 Pathways.
AB  - OBJECTIVES: Osteoarthritis (OA) is a chronic joint disease, characterized by a
      progressive loss of articular cartilage. During OA, proinflammatory cytokines,
      such as interleukin IL-1, induce the expression of matrix metalloproteinases
      (MMPs) in chondrocytes, contributing thus to the extracellular matrix (ECM)
      degradation. Members of Serpine family, including plasminogen activator
      inhibitors have been reported to participate in ECM regulation. The aim of this
      study was to assess the expression of serpin peptidase inhibitor clade E member 2
      (SERPINE2), under basal conditions and in response to increasing doses of IL
      1alpha, in human cultured chondrocytes. We also examined the effects of SERPINE2
      on IL-1alpha-induced MMP-13 expression. For completeness, the signaling pathway
      involved in this process was also explored. METHODS: SERPINE2 mRNA and protein
      expression were evaluated by RT-qPCR and western blot analysis in human T/C-28a2
      cell line and human primary chondrocytes. These cells were treated with human
      recombinant SERPINE2, alone or in combination with IL-1alpha. ERK 1/2, NFkappaB
      and AP-1 activation were assessed by western blot analysis. RESULTS: Human
      cultured chondrocytes express SERPINE2 in basal condition. This expression
      increased in response to IL-1alpha stimulation. In addition, recombinant SERPINE2
      induced a clear inhibition of MMP-13 expression in IL-1alpha-stimulated
      chondrocytes. This inhibitory effect is likely regulated through a pathway
      involving ERK 1/2, NF-kappaB and AP-1. CONCLUSIONS: Taken together, these data
      demonstrate that SERPINE2 might prevent cartilage catabolism by inhibiting the
      expression of MMP-13, one of the most relevant collagenases, involved in
      cartilage breakdown in OA.

PMID- 26305373
TI  - De Novo Transcriptome Analysis of Warburgia ugandensis to Identify Genes Involved
      in Terpenoids and Unsaturated Fatty Acids Biosynthesis.
AB  - The bark of Warburgia ugandensis (Canellaceae family) has been used as a
      medicinal source for a long history in many African countries. The presence of
      diverse terpenoids and abundant polyunsaturated fatty acids (PUFAs) in this organ
      contributes to its broad range of pharmacological properties. Despite its
      medicinal and economic importance, the knowledge on the biosynthesis of terpenoid
      and unsaturated fatty acid in W. ugandensis bark remains largely unknown.
      Therefore, it is necessary to construct a genomic and/or transcriptomic database
      for the functional genomics study on W. ugandensis. The chemical profiles of
      terpenoids and fatty acids between the bark and leaves of W. ugandensis were
      compared by gas chromatography-mass spectrometry (GC-MS) analysis. Meanwhile, the
      transcriptome database derived from both tissues was created using Illumina
      sequencing technology. In total, about 17.1 G clean nucleotides were obtained,
      and de novo assembled into 72,591 unigenes, of which about 38.06% can be aligned
      to the NCBI non-redundant protein database. Many candidate genes in the
      biosynthetic pathways of terpenoids and unsaturated fatty acids were identified,
      including 14 unigenes for terpene synthases. Furthermore, 2,324 unigenes were
      discovered to be differentially expressed between both tissues; the functions of
      those differentially expressed genes (DEGs) were predicted by gene ontology
      enrichment and metabolic pathway enrichment analyses. In addition, the expression
      of 12 DEGs with putative roles in terpenoid and unsaturated fatty acid metabolic
      pathways was confirmed by qRT-PCRs, which was consistent with the data of the RNA
      sequencing. In conclusion, we constructed a comprehensive transcriptome dataset
      derived from the bark and leaf of W. ugandensis, which forms the basis for
      functional genomics studies on this plant species. Particularly, the comparative
      analysis of the transcriptome data between the bark and leaf will provide
      critical clues to reveal the regulatory mechanisms underlying the biosynthesis of
      terpenoids and PUFAs in W. ugandensis. 

PMID- 26305374
TI  - Assessing the Efficacy of Restricting Access to Barbecue Charcoal for Suicide
      Prevention in Taiwan: A Community-Based Intervention Trial.
AB  - OBJECTIVE: Charcoal-burning suicide has recently been spreading to many Asian
      countries. There have also been several cases involving this new method of
      suicide in Western countries. Restricting access to suicide means is one of the
      few suicide-prevention measures that have been supported by empirical evidence.
      The current study aims to assess the effectiveness of a community intervention
      program that restricts access to charcoal to prevent suicide in Taiwan. METHODS
      AND FINDINGS: A quasi-experimental design is used to compare method-specific
      (charcoal-burning suicide, non-charcoal-burning suicide) and overall suicide
      rates in New Taipei City (the intervention site, with a population of 3.9
      million) with two other cities (Taipei City and Kaohsiung City, the control
      sites, each with 2.7 million residents) before (Jan 1st 2009- April 30th 2012)
      and after (May 1st 2012-Dec. 31st 2013) the initiation of a charcoal-restriction
      program on May 1st 2012. The program mandates the removal of barbecue charcoal
      from open shelves to locked storage in major retail stores in New Taipei City. No
      such restriction measure was implemented in the two control sites. Generalized
      linear regression models incorporating secular trends were used to compare the
      changes in method-specific and overall suicide rates before and after the
      initiation of the restriction measure. A simulation approach was used to estimate
      the number of lives saved by the intervention. Compared with the pre-intervention
      period, the estimated rate reduction of charcoal-burning suicide in New Taipei
      City was 37% (95% CI: 17%, 50%) after the intervention. Taking secular trends
      into account, the reduction was 30% (95% CI: 14%, 44%). No compensatory rise in
      non-charcoal-burning suicide was observed in New Taipei City. No significant
      reduction in charcoal-burning suicide was observed in the other two control
      sites. The simulation approach estimated that 91 (95%CI [55, 128]) lives in New
      Taipei City were saved during the 20 months of the intervention. CONCLUSION: Our
      results demonstrate that the charcoal-restriction program reduced method-specific
      and overall suicides. This study provides strong empirical evidence that
      restricting the accessibility of common lethal methods of suicide can effectively
      reduce suicide rates.

PMID- 26305375
TI  - Abdominal Respiration Induces Hemodilution and Related Reduction in ADH
      Concentration of Blood.
AB  - To establish effective lymph drainage methods and develop concise and accurate
      clinical techniques for evaluating lymph drainage in healthy individuals and
      patients with cancer treatment-related lymph edema, we investigated the numbers
      of red (RBC) and white (WBC) blood cells, and platelets (PLT) in blood,
      hematocrit (Ht), and the blood concentrations of total protein (TP), albumin
      (Alb), and anti-diuretic hormone (ADH) before and after 5 min manual lymph
      drainage, followed by 30 min rest with or without abdominal respiration in the
      supine or sitting position in 48 healthy volunteers. The 5 min facial, upper and
      lower extremities lymph drainage, followed by 30 min rest in the supine position
      induced significant reductions of the TP and Alb in all subjects, and their RBC
      and Ht levels in some subjects. The 30 min rest only in the supine position
      without lymph drainage produced also significant reductions of blood TP and Alb.
      In addition, abdominal respiration in the supine position without manual lymph
      drainage caused more significant hemodilution, being significant reductions of
      TP, Alb, RBC, Ht, and ADH in all volunteers. These findings may be related to
      effective lymph drainage from the chylocyst. Furthermore, it also resulted in a
      significantly increased micturition desire. In conclusion, abdominal respiration
      during 30 min rest in the supine position is effective at inducing lymph
      drainage, and the associated induction of hemodilution and lowering of the blood
      ADH concentration (and increased micturition desire in some cases) can be used to
      accurately assess the extent of lymph drainage.

PMID- 26305377
TI  - Two New Species of Liuixalus (Rhacophoridae, Anura): Evidence from Morphological
      and Molecular Analyses.
AB  - Due to small body sizes, superficial similarities in morphologies, and obscure
      activity behaviors, the phylogeny and taxonomy of species in the genus Liuixalus
      were very troublesome. Some species might comprise a complex of cryptic species.
      To investigate the species of group, we constructed the matrilineal genealogy of
      the genus using 16s rRNA mitochondrial DNA sequences. Analyses recovered six well
      supported matrilines that involved L. romeri, L. ocellatus, L. hainanus, L.
      calcarius, Liuixalus shiwandashan sp. nov. and Liuixalus jinxiuensis sp. nov.,
      though the historical relationships among them remained unresolved. Currently,
      Liuixalus included 4 species, distributed eastwards from northern Vietnam to Hong
      Kong, China. Based on genealogical and morphological distinctiveness, we
      described Liuixalus jinxiuensis sp. nov. from the type locality Mt. Dayao,
      Jinxiu, China and Liuixalus shiwandashan sp. nov. from the type locality Mt.
      Shiwanda, China. A combination of morphological measurements, genetic,
      bioacoustic and osteological analysis was served to diagnose the new taxa. 

PMID- 26305376
TI  - A Physical Interaction between the Dopamine Transporter and DJ-1 Facilitates
      Increased Dopamine Reuptake.
AB  - The regulation of the dopamine transporter (DAT) impacts extracellular dopamine
      levels after release from dopaminergic neurons. Furthermore, a variety of protein
      partners have been identified that can interact with and modulate DAT function.
      In this study we show that DJ-1 can potentially modulate DAT function. Co
      expression of DAT and DJ-1 in HEK-293T cells leads to an increase in [3H]
      dopamine uptake that does not appear to be mediated by increased total DAT
      expression but rather through an increase in DAT cell surface localization. In
      addition, through a series of GST affinity purifications and co
      immunoprecipitations, we provide evidence that the DAT can be found in a complex
      with DJ-1, which involve distinct regions within both DAT and DJ-1. Using in
      vitro binding experiments we also show that this complex can be formed in part by
      a direct interaction between DAT and DJ-1. Co-expression of a mini-gene that can
      disrupt the DAT/DJ-1 complex appears to block the increase in [3H] dopamine
      uptake by DJ-1. Mutations in DJ-1 have been linked to familial forms of
      Parkinson's disease, yet the normal physiological function of DJ-1 remains
      unclear. Our study suggests that DJ-1 may also play a role in regulating dopamine
      levels by modifying DAT activity. 

PMID- 26305379
TI  - Attenuation of Oxidative Stress by Ischemic Preconditioning in an Experimental
      Model of Intraabdominal Hypertension.
AB  - PURPOSE: Increased intra-abdominal pressure, as used in laparoscopic surgery or
      seen in intraabdominal hypertension (IAH), is associated with tissue ischemia and
      oxidative stress. Ischemic preconditioning (IP) is a method successfully used in
      liver and transplant surgery, in order to attenuate the detrimental effects of
      ischemia and reperfusion. In this experimental study, we tested the ability of IP
      to modify oxidative stress induced by extremely high intraabdominal pressures.
      METHODS: Twenty-five female pigs were studied and divided in three groups: a
      control group, a pneumoperitoneum group (with pressure of 30 mmHg), and an
      ischemic preconditioning group (initially subjected to preconditioning with
      pressure of 25 mmHg for 15 min and desufflation for 15 min and then to
      pneumoperitoneum as in pneumoperitoneum group). Blood samples were obtained at
      identical time intervals in the three groups. Total oxidative capacity, total
      antioxidative capacity and total nitric oxide (NO), nitrite and nitrate
      concentrations were measured and compared between groups. RESULTS: IP increased
      total antioxidative capacity (p = .045) and protective mediators like nitrite (p
      = .022). It was also associated with a trend toward lower levels of total
      oxidative capacity at the end of the abdominal desufflation period but
      statistical significance was not met. CONCLUSIONS: IP attenuated oxidative stress
      induced by IAH, mainly by increasing antioxidative capacity and the levels of
      protective mediators. The fact that IP was effective, even when used at extremely
      high levels of intraabdominal pressure, reinforces the interest on this method
      but further studies are needed to clarify its mechanism of action and potential
      clinical applications.

PMID- 26305378
TI  - Comparative genomics of Fusarium oxysporum f. sp. melonis reveals the secreted
      protein recognized by the Fom-2 resistance gene in melon.
AB  - Development of resistant crops is the most effective way to control plant
      diseases to safeguard food and feed production. Disease resistance is commonly
      based on resistance genes, which generally mediate the recognition of small
      proteins secreted by invading pathogens. These proteins secreted by pathogens are
      called 'avirulence' proteins. Their identification is important for being able to
      assess the usefulness and durability of resistance genes in agricultural
      settings. We have used genome sequencing of a set of strains of the melon wilt
      fungus Fusarium oxysporum f. sp. melonis (Fom), bioinformatics-based genome
      comparison and genetic transformation of the fungus to identify AVRFOM2, the gene
      that encodes the avirulence protein recognized by the melon Fom-2 gene. Both an
      unbiased and a candidate gene approach identified a single candidate for the
      AVRFOM2 gene. Genetic complementation of AVRFOM2 in three different race 2
      isolates resulted in resistance of Fom-2-harbouring melon cultivars. AvrFom2 is a
      small, secreted protein with two cysteine residues and weak similarity to
      secreted proteins of other fungi. The identification of AVRFOM2 will not only be
      helpful to select melon cultivars to avoid melon Fusarium wilt, but also to
      monitor how quickly a Fom population can adapt to deployment of Fom-2-containing
      cultivars in the field. 

PMID- 26305381
TI  - "We Don't Get Into All That": An Analysis of How Teachers Uphold Heteronormative
      Sex and Relationship Education.
AB  - Legislation that applies to UK SRE currently advocates inclusive provision. Given
      the nonstatutory status of SRE, however, it is unclear how teachers incorporate
      sexual inclusivity, especially as research has shown that teachers' discursive
      practices can promote a heteronormative SRE climate (Renn, 2010). Using a
      discursive psychological approach to analyze interview data, this study examined
      how teachers account for their provision as inclusive. It was revealed that even
      when promoting their inclusivity, teachers' SRE provision upholds
      heteronormativity. In doing this, they positioned LGB and same-sex practices
      outside of the classroom, potentially leaving these young people without a
      sufficient sex education. 

PMID- 26305380
TI  - Differential responses of gut microbiota to the same prebiotic formula in
      oligotrophic and eutrophic batch fermentation systems.
AB  - The same prebiotics have produced inconsistent effects on microbiota when
      evaluated in different batch fermentation studies. To understand the reasons
      behind these discrepancies, we compared impact of one prebiotic formula on the
      same inoculated fecal microbiota in two frequently used batch systems: phosphate
      buffered saline (PBS, oligotrophic) and basal culture medium (BCM, eutrophic).
      The microbiota was monitored using 454 pyrosequencing. Negative controls (no
      prebiotic) of both systems showed significant shifts in the microbiota during
      fermentation, although their pH remained relatively stable, especially in BCM,
      with increases in Bilophila and Escherichia/Shigella but a decrease in
      Faecalibacterium. We identified prebiotic responders via redundancy analysis by
      including both baseline and negative controls. The key positive and negative
      responders in the two systems were very different, with only 8 consistently
      modulated OTUs (7 of the 28 positive responders and 1 of the 35 negative
      responders). Moreover, some OTUs within the same genus responded to the prebiotic
      in opposite ways. Therefore, to obtain a complete in vitro evaluation of the
      modulatory effects of a prebiotic on microbiota, it is necessary to use both
      oligotrophic and eutrophic systems, compare treatment groups with both baseline
      and negative controls, and analyze the microbiota changes down to the OTU level. 

PMID- 26305382
TI  - Effects of an energy-dense diet and nicotinic acid supplementation on production
      and metabolic variables of primiparous or multiparous cows in periparturient
      period.
AB  - It is well observed that feeding energy-dense diets in dairy cows during the dry
      period can cause metabolic imbalances after parturition. Especially dairy cows
      with high body condition score (BCS) and fed an energy-dense diet were prone to
      develop production diseases due to metabolic disturbances postpartum. An
      experiment was conducted to determine the effects of an energy-dense diet and
      nicotinic acid (NA) on production and metabolic variables of primiparous and
      multiparous cows in late pregnancy and early lactation which were not pre
      selected for high BCS. Thirty-six multiparous and 20 primiparous German Holstein
      cows with equal body conditions were fed with energy-dense (60% concentrate/40%
      roughage mixture; HC group) or adequate (30% concentrate/70% roughage mixture; LC
      group) diets prepartum. After parturition, concentrate proportion was dropped to
      30% for all HC and LC groups and was increased to 50% within 16 days for LC and
      within 24 days for HC cows. In addition, half of the cows per group received 24 g
      NA supplement per day and cow aimed to attenuate the lipid mobilisation
      postpartum. Feeding energy-dense diets to late-pregnant dairy cows elevated the
      dry matter (p < 0.001) and energy intake (p < 0.001) as well as the energy
      balance (p < 0.001) without affecting the BCS (p = 0.265) during this period.
      However, this did not result in any metabolic deviation postpartum as the effects
      of prepartum concentrate feeding were not carried over into postpartum period.
      Multiparous cows responded more profoundly to energy-dense feeding prepartum
      compared with primiparous cows, and parity-related differences in the transition
      from late pregnancy to lactation were obvious pre- and postpartum. The
      supplementation with 24 g NA did not reveal any effect on energy metabolism. This
      study clearly showed that energy-dense feeding prepartum did not result in
      metabolic imbalances postpartum in multiparous and primiparous cows not selected
      for high BCS. A genetic predisposition for an anabolic metabolic status as
      indicated by high BCS may be crucial for developing production diseases at the
      onset of lactation. 

PMID- 26305383
TI  - Effects of supplementation of rumen-protected choline on growth performance, meat
      quality and gene expression in longissimus dorsi muscle of lambs.
AB  - This study determined the effects of rumen-protected choline (RPC) on growth
      performance, blood lipids, meat quality and expression of genes involved in fatty
      acid metabolism in young lambs. A total of 24 Dorper * Hu lambs (about 20 kg body
      weight) were kept in individual pens and fed diets with 0%, 0.25%, 0.50% and
      0.75% RPC for 60 d. Supplementation of 0.25% RPC increased average daily gain of
      lambs, whereas treatments had no significant effect on feed intake. The pH values
      of meat were increased at 0.25% RPC and both, dripping loss and shear force of
      meat, were significantly decreased in RPC-supplemented lambs. No significant
      changes were observed for dressing percentage and intramuscular fat. RPC
      supplementations had no significant effect on the concentrations of triglycerides
      and cholesterols in serum, but the concentration of high-density lipoprotein was
      decreased at 0.50% RPC and that of low-density lipoprotein was increased at 0.75%
      RPC. In m. longissimus dorsi, the expressions of cluster of differentiation 36
      (CD36), acetyl-CoA carboxylase (ACC) and fatty-acid synthase (FASN) genes were
      increased at 0.25% RPC. Supplementation of 0.75% RPC increased the expressions of
      lipoprotein lipase (LPL) and FASN genes, decreased the expression of ACC gene and
      had no effect on CD36 gene. The results of this study showed that supplementation
      of 0.25% RPC could promote growth performance of lambs and improve meat quality.
      This may be mediated by effects on blood lipid profiles and the metabolism of
      fatty acids in skeleton muscles. However, the beneficial effects of 0.25% RPC
      supplementation need to be validated with a larger number of animals. Higher
      doses, particularly 0.75% RPC, showed adverse effects on live weight gain and ACC
      expression. 

PMID- 26305384
TI  - Estimation of utilisable crude protein at the duodenum of dried distillers'
      grains with solubles using a modified gas test.
AB  - The objective of this study was to characterise the variation of utilisable crude
      protein at the duodenum (uCP) of dried distillers' grains with solubles (DDGS)
      for ruminants using a modified gas test and to predict the uCP in DDGS based on
      chemical composition. Thirteen samples originating from wheat, maize, barley or
      blends of different substrates were studied. The in vitro uCP was estimated using
      the modified Hohenheim gas test (moHGT). Samples were incubated in rumen fluid
      for 8 h, 24 h and 48 h followed by ammonia distillation. The obtained values were
      compared to reference values of uCP (based on the contents of crude protein (CP),
      in situ undegraded CP and metabolisable energy). The reference and in vitro
      values of uCP were calculated according to passage rates of 2, 5 and 8%/h (i.e.,
      uCP2, uCP5 and uCP8, respectively). The in vitro uCP8 ranged from 214 to 320 g/kg
      DM and reference values from 158 to 302 g/kg DM. The in vitro uCP2 was on average
      lower (by 7 g/kg DM) and in vitro uCP8 was higher (by 56 g/kg DM) than their
      respective reference values. The in vitro uCP5 and uCP8 were correlated with
      reference values and the correlations were improved with increasing passage
      rates. When the differences of uCP content between in vitro and reference values
      were related to CP fractions, they increased with increasing content of CP
      fraction A and decreasing content of CP fraction B3 for uCP8. The prediction of
      uCP values from chemical composition was not reliable. It was concluded that uCP
      can be predicted on the basis of the moHGT method and CP fractions. The accuracy
      of prediction improved upon the inclusion of CP fractions and neutral-detergent
      insoluble nitrogen. The present study revealed a significant variation in the uCP
      content of DDGS, which should be considered when formulating rations for dairy
      cows. 

PMID- 26305385
TI  - Influence of formula versus sow milk feeding on trace element status and
      expression of zinc-related genes in the jejunum, liver and pancreas of neonatal
      piglets.
AB  - Increasing litter sizes in modern swine production have raised an urgent need for
      artificial rearing strategies and formula feeding. The current experiment was
      conducted to study the influence of formula trace element concentration according
      to recommendations for weaned piglets on the mRNA concentration of zinc (Zn)
      related genes in the jejunum, liver and pancreas of neonatal piglets. Eight
      artificially reared piglets were fed a cow-milk-based formula (Group FO)
      containing 100 mg Zn/kg dry matter. Eight of their sow-reared littermates (Group
      SM) were used as control. After 14 d, all 16 piglets were killed and the jejunum,
      liver and pancreas were evaluated for Zn, copper, manganese (Mn) and iron (Fe)
      concentration and mRNA concentration of metal and Zn-specific transporters,
      metallothioneins (MT) and interleukin 6 (IL-6). In Group FO the Zn concentration
      in liver tissue was increased (p < 0.05). Furthermore, Fe and Mn concentrations
      in liver and jejunal tissue were higher (p < 0.05) in Group FO, whereas neither
      Zn transporters nor MT in jejunal and pancreatic tissue showed differences
      between both groups. In the liver of Group FO, MT mRNA concentration was higher
      (p < 0.05), whereas Zn transporter protein 1 and divalent metal-ion transporter 1
      (DMT1) mRNA concentration was lower (p < 0.05). Besides Zn-induced expression of
      transporters and MT, the significantly increased IL-6 expression in Group FO
      suggests the involvement of cytokine-mediated Mn and Fe sequestration in the
      liver and jejunum. The results revealed that dietary trace element concentration
      used in the study likely exceeded the requirements of neonatal pigs as reflected
      by homeostatic counter-regulation in different organs. 

PMID- 26305386
TI  - Fermented and extruded wheat bran in piglet diets: impact on performance,
      intestinal morphology, microbial metabolites in chyme and blood lipid radicals.
AB  - The aim of the present study was to evaluate the influence of native, fermented
      and extruded wheat bran on the performance and intestinal morphology of piglets.
      Additionally, short-chain fatty acids (SCFA), biogenic amines, ammonia, lactic
      acid, pH as well as E. coli and lactic acid bacterial counts were analysed in
      digesta samples from three gut sections. Furthermore, the antioxidant potential
      in blood samples was evaluated based on the lipid radicals formed. For this
      purpose, 48 newly weaned piglets (28 d old) were allocated to one of the four
      different dietary treatment groups: no wheat bran (Control), native wheat bran,
      fermented wheat bran as well as extruded wheat bran. Wheat bran variants were
      included at 150 g/kg into the diets. All diets were mixed to reach the calculated
      isonitrogenic nutrient contents. Gut tissue and digesta samples were collected
      from the proximal jejunum, the terminal ileum and the colon ascendens, blood
      samples directly at slaughter. Although none of the dietary interventions had an
      impact on performance parameters, the amount of goblet cells in the ileum was
      increased upon feeding native and extruded wheat bran, compared to fermented bran
      (p < 0.05). The E. coli counts in colonic chyme were significantly lower (p <
      0.05) in the Control group compared to the groups fed with wheat bran. The
      concentration of SCFA showed differences for minor compounds (p < 0.05), while
      linear contrast analyses revealed a reduced concentration of total SCFA in the
      colon following the feeding of modified wheat bran compared to native wheat bran.
      This may suggest that several compounds are more easily digested already in the
      ileum, resulting in a reduced nutrient flow into the large intestine and
      therefore less unexploited digesta is available as substrate for the
      microorganisms there. Fermentation also resulted in a significant decrease of
      methylamine in the colon (p < 0.05), while other biogenic amines in the ileum and
      colon showed no statistically significant differences. The formation of lipid
      radicals was decreased (p < 0.05) after feeding native wheat bran compared to the
      Control group. These results suggest that fermentation and extrusion of wheat
      bran exert some different impact regarding their physiological mode of action. 

PMID- 26305387
TI  - Effect of a negative energy balance induced by feed restriction in lactating sows
      on hepatic lipid metabolism, milk production and development of litters.
AB  - In rodents, forced activation of hepatic peroxisome proliferator-activated
      receptor alpha (PPARalpha) by administration of exogenous PPARalpha activators
      during lactation leads to a reduction of milk triacylglycerol (TAG) production.
      Herein, we investigated whether a negative energy balance (NEB) induced by feed
      restriction (about 18% lower feed and energy intake) during lactation by
      increasing the release of fatty acids, which act as PPARalpha agonists, causes a
      disruption of hepatic lipid metabolism and thereby impairs milk TAG production in
      sows. Nutrient and energy content of the milk on day 20 of lactation and gains of
      litters during the first 14 d and the whole 21 d suckling period did not differ
      between Control and feed-restricted sows. The mRNA concentrations of several
      sterol regulatory element-binding protein target genes involved in lipid
      synthesis in the liver and the plasma concentration of TAG were reduced in the
      feed-restricted sows, whereas the mRNA concentrations of PPARalpha target genes
      involved in fatty acid oxidation in liver and skeletal muscle were not different
      between groups. In conclusion, it was shown that an NEB during lactation does not
      adversely affect milk composition and gains of litters, despite inhibiting
      hepatic expression of genes involved in lipid synthesis and reducing plasma TAG
      concentration. The finding that PPARalpha target genes involved in fatty acid
      utilisation in liver and muscle of sows are not induced by the NEB during
      lactation may explain that fatty acid availability in the mammary gland is
      sufficient to maintain milk TAG production and to allow normal litter gain. 

PMID- 26305388
TI  - Effect of a negative energy balance induced by feed restriction on pro
      inflammatory and endoplasmic reticulum stress signalling pathways in the liver
      and skeletal muscle of lactating sows.
AB  - High-producing sows develop typical signs of an inflammatory condition and
      endoplasmic reticulum (ER) stress in the liver during lactation. At present, it
      is unknown whether a negative energy balance (NEB) is causative for this.
      Therefore, an experiment with lactating sows, which were either restricted in
      their feed intake to 82% of their energy requirement (Group FR) or were fed to
      meet their energy requirement (Control), was performed and the effect on ER
      stress-induced unfolded protein response (UPR), nuclear factor kappa B (NF
      kappaB), nuclear factor E2-related factor 2 (Nrf2) and NOD-like receptor P3
      (NLRP3) inflammasome signalling in the liver was evaluated. Relative mRNA
      concentrations of several genes involved in ER stress-induced UPR, NF-kappaB and
      NLRP3 inflammasome signalling were reduced in the liver of Group FR compared to
      the Control group. Plasma concentrations of haptoglobin and C-reactive protein
      were 13% and 37%, respectively, lower in Group FR than in the Control group, but
      these differences were not significant. In conclusion, feed restriction in
      lactating sows inhibits pro-inflammatory and ER stress signalling pathways in the
      liver, which suggests that not the NEB per se is causative for inflammation and
      ER stress induction in the liver of lactating sows. Rather it is likely that ER
      stress during lactation is the consequence of the presence of potent pro
      inflammatory and ER stress-inducing stimuli, such as cytokines, reactive oxygen
      species and microbial components, which enter the circulation as a result of
      infectious diseases that frequently occur in sows after farrowing. 

PMID- 26305389
TI  - Base-promoted coupling of carbon dioxide, amines, and diaryliodonium salts: a
      phosgene- and metal-free route to O-aryl carbamates.
AB  - A phosgene- and metal-free synthesis of O-aryl carbamates is realized through a
      three-component coupling of carbon dioxide, amines and diaryliodonium salts. The
      reaction only requires a base as the promoter, providing access to a diverse
      array of O-aryl carbamates in moderate to high yields with excellent
      chemoselectivity. 

PMID- 26305390
TI  - Randomized Evaluation of Glycemic Control in the Medical Intensive Care Unit
      Using Real-Time Continuous Glucose Monitoring (REGIMEN Trial).
AB  - BACKGROUND AND OBJECTIVE: Hyperglycemia occurs commonly in patients admitted to
      medical intensive care units (MICUs). Whether real-time (RT) continuous glucose
      monitoring (CGM) improves glycemic control and variability and reduces
      hypoglycemia in severely ill MICU patients with an Acute Physiology and Chronic
      Health Evaluation II (APACHE-II) score of >=20 has not been studied. SUBJECTS AND
      METHODS: Thirty-five patients (66 +/- 10 years of age; APACHE-II score, 28 +/- 6)
      were randomly assigned to RT-CGM (n = 16) using the GlucoDay((r))S (A. Menarini
      Diagnostics, Florence, Italy) device or to blinded CGM. Insulin was infused using
      a modified Yale protocol targeting a blood glucose level between 80 and 120
      mg/dL. Outcome measures were percentage of time in normoglycemia (80-110 mg/dL)
      and in hypoglycemia (<60 mg/dL), glycemic variability (SD, coefficient of
      variation, mean amplitude of glucose excursions, and mean of daily differences),
      and CGM accuracy (error grid analyses, Bland-Altman bias plot, and mean absolute
      relative deviation). RESULTS: During 96 h of monitoring, glycemia reached target
      (80-110 mg/dL) in 37 +/- 15%, was between 70 and 180 mg/dL in 91 +/- 10%, and <60
      mg/dL in 2 +/- 2% of the time. In the RT-CGM group glycemia averaged 119 +/- 17
      mg/dL versus 122 +/- 11 mg/dL in the control group. Parameters of glucose
      variability and percentages of time at target glycemia and in hypoglycemia were
      similar between groups. GlucoDayS values and arterial glycemia correlated well,
      with 98.6% of data falling in Zones A and B of the error grid analysis. Mean
      absolute relative devation was 11.2%. CONCLUSIONS: RT-CGM did not ameliorate
      glucose control or variability; neither did it reduce the number of hypoglycemic
      events, but our insulin infusion protocol led to overall good glucose control
      without a significant hypoglycemia risk, making further improvement difficult.

PMID- 26305392
TI  - How Do DSM-5 Personality Traits Align With Schema Therapy Constructs?
AB  - DSM-5 offers an alternative model of personality pathology that includes 25
      traits. Although personality disorders are mostly treated with psychotherapy, the
      correspondence between DSM-5 traits and concepts in evidence-based psychotherapy
      has not yet been evaluated adequately. Suitably, schema therapy was developed for
      treating personality disorders, and it has achieved promising evidence. The
      authors examined associations between DSM-5 traits and schema therapy constructs
      in a mixed sample of 662 adults, including 312 clinical participants.
      Associations were investigated in terms of factor loadings and regression
      coefficients in relation to five domains, followed by specific correlations among
      all constructs. The results indicated conceptually coherent associations, and 15
      of 25 traits were strongly related to relevant schema therapy constructs.
      Conclusively, DSM-5 traits may be considered expressions of schema therapy
      constructs, which psychotherapists might take advantage of in terms of case
      formulation and targets of treatment. In turn, schema therapy constructs add
      theoretical understanding to DSM-5 traits.

PMID- 26305391
TI  - Pre-school obesity is inversely associated with vegetable intake, grocery stores
      and outdoor play.
AB  - The study determined the association between body mass index (BMI) z score and
      fruit and vegetable intake, frequency and ratio of fast food outlets and grocery
      stores in concentric areas around the child's residence, outdoor play and total
      crime index. Data from 78 Louisiana pre-school children were analyzed using
      Pearson's correlation and multiple regression analysis. Parental-reported fruit
      intake was linearly associated with increased number of grocery store counts in
      concentric areas around the child's residence (P = 0.0406, P = 0.0281). Vegetable
      intake was inversely (P = 0.04) and the ratio of fast food outlets to grocery
      stores in a 2-mile concentric area around the child's residence was positively (P
      = 0.05) associated to BMI z score after applying Best Model regression analysis
      (F = 3.06, P = 0.0346). Children residing in neighbourhoods with greater access
      to fast foods and lower access to fruits and vegetables may be at higher risk for
      developing obesity during pre-school years.

PMID- 26305393
TI  - Effects of Personality Disorders on Self-Other Agreement and Favorableness in
      Personality Descriptions.
AB  - The authors studied effects of self-reported personality disorder (PD) symptoms
      on interpersonal perception, particularly self-other agreement and favorableness.
      Using a round-robin design, 52 groups of four well-acquainted students described
      themselves and each other on a measure of the Five-Factor model of personality
      and were administered a self-report screening instrument for DSM-IV (Axis 2).
      Using the Social Accuracy Model, the peer reports were predicted, across items,
      from either (a) the target person's self-reports plus the self-report item means,
      or (b) the items' social desirability. This resulted in separate coefficients for
      each peer-target dyad, indicating either self-other agreement or favorableness.
      These coefficients were then predicted from the PD scores of the target and the
      peer, using multilevel modeling. Main findings were that persons scoring high on
      PD measures agreed less with their peers on their unique personality
      characteristics, and that such persons were described by, and described their
      peers, less favorably.

PMID- 26305394
TI  - The Influence of Posttraumatic Stress Disorder on Treatment Outcomes of Patients
      With Borderline Personality Disorder.
AB  - The aim of this study was to determine the influence of posttraumatic stress
      disorder (PTSD) on treatment outcomes in patients with borderline personality
      disorder (BPD). Participants were 180 individuals diagnosed with BPD enrolled in
      a randomized controlled trial that compared the clinical and cost effectiveness
      of dialectical behavior therapy (DBT) and general psychiatric management (GPM).
      Multilevel linear models and generalized linear models were used to compare
      clinical outcomes of BPD patients with and without PTSD. BPD patients with
      comorbid PTSD reported significantly higher levels of global psychological
      distress at baseline and end of treatment compared to their non-PTSD
      counterparts. Both groups evidenced comparable rates of change on suicide
      attempts and non-suicidal self-injury (NSSI), global psychological distress, and
      BPD symptoms over the course of treatment and post-treatment follow-up. DBT and
      GPM were effective for BPD patients with and without PTSD across a broad range of
      outcomes.

PMID- 26305395
TI  - Acting and Feeling Like a Vulnerable Child, an Internalized "Bad" Parent, or a
      Healthy Person: The Assessment of Schema Modes in Non-Clinical Adolescents.
AB  - Schema modes are strong, predominant, momentary (state-like) emotional and
      cognitive states, and maladaptive coping responses that occur when underlying
      personality schemas are activated by emotional events. The current study employed
      the Schema Mode Inventory for Adolescents (SMI-A) to assess such schema modes in
      a sample of non-clinical adolescents (n = 530). Confirmatory factor analysis
      revealed that the hypothesized model of the SMI-A with 14 separate schema modes
      provided a good fit for the data. Reliability coefficients for the various schema
      modes were all in the adequate to good range. Finally, the validity of the SMI-A
      was supported by significant and meaningful relations between schema modes on the
      one hand and early maladaptive schema domains, symptoms of psychopathology, and
      quality of life on the other. Taken together, the psychometric properties of the
      SMI-A are promising, and the SMI-A can be considered a viable instrument to
      assess schema modes in adolescents.

PMID- 26305397
TI  - Corrigendum to "The complete mitochondrial genome of the gnomefish Scombrops
      boops (Teleostei, Perciformes, Scombropidae) from the Pacific Ocean off the
      Japanese Islands" [Mitochondrial DNA.
      http://dx.doi.org/10.3109/19401736.2014.987242].

PMID- 26305396
TI  - Cost-Effectiveness of Short-Term Inpatient Psychotherapy Based on Transactional
      Analysis in Patients With Personality Disorder.
AB  - Short-term inpatient psychotherapy based on transactional analysis (STIP-TA) in
      patients with personality disorders (PD) has shown to be more effective than
      comparable other specialized psychotherapies (OP). The aim of this study was to
      assess whether the higher effectiveness of STIP-TA also results in a better cost
      effectiveness. Patients treated with STIP-TA were matched with patients treated
      with OP by the propensity score. Healthcare costs and lost productivity costs
      were measured over 3 years and from the societal perspective. Cost-effectiveness
      was represented by costs per quality adjusted life years (QALYs). Uncertainty was
      assessed using bootstrapping. Mean 3-year costs were ?59,834 for STIP-TA and
      ?69,337 for OP, a difference of -?9,503, 95% CI [-32,561, 15,726]. QALYs were
      2.29 for STIP-TA and 2.05 for OP, a difference of .24, 95% CI [.05, .44]. STIP-TA
      is a dominant treatment compared to OP: less costly and more effective. We
      conclude that STIP-TA is a cost-effective treatment in PD patients. 

PMID- 26305398
TI  - Discriminating a Single Nucleotide Difference for Enhanced miRNA Detection Using
      Tunable Graphene and Oligonucleotide Nanodevices.
AB  - In this study we have reported our efforts to address some of the challenges in
      the detection of miRNAs using water-soluble graphene oxide and DNA
      nanoassemblies. Purposefully inserting mismatches at specific positions in our
      DNA (probe) strands shows increasing specificity against our target miRNA, miR
      10b, over miR-10a which varies by only a single nucleotide. This increased
      specificity came at a loss of signal intensity within the system, but we
      demonstrated that this could be addressed with the use of DNase I, an
      endonuclease capable of cleaving the DNA strands of the RNA/DNA heteroduplex and
      recycling the RNA target to hybridize to another probe strand. As we previously
      demonstrated, this enzymatic signal also comes with an inherent activity of the
      enzyme on the surface-adsorbed probe strands. To remove this activity of DNase I
      and the steady nonspecific increase in the fluorescence signal without
      compromising the recovered signal, we attached a thermoresponsive PEGMA polymer
      (poly(ethylene glycol) methyl ether methacrylate) to nGO. This smart polymer is
      able to shield the probes adsorbed on the nGO surface from the DNase I activity
      and is capable of tuning the detection capacity of the nGO nanoassembly with a
      thermoswitch at 39  degrees C. By utilizing probes with multiple mismatches,
      DNase I cleavage of the DNA probe strands, and the attachment of PEGMA polymers
      to graphene oxide to block undesired DNase I activity, we were able to detect miR
      10b from liquid biopsy mimics and breast cancer cell lines. Overall we have
      reported our efforts to improve the specificity, increase the sensitivity, and
      eliminate the undesired enzymatic activity of DNase I on surface-adsorbed probes
      for miR-10b detection using water-soluble graphene nanodevices. Even though we
      have demonstrated only the discrimination of miR-10b from miR-10a, our approach
      can be extended to other short RNA molecules which differ by a single nucleotide.

PMID- 26305400
TI  - Detection of Test Speededness Using Change-Point Analysis.
AB  - Change-point analysis (CPA) is a well-established statistical method to detect
      abrupt changes, if any, in a sequence of data. In this paper, we propose a
      procedure based on CPA to detect test speededness. This procedure is not only
      able to classify examinees into speeded and non-speeded groups, but also identify
      the point at which an examinee starts to speed. Identification of the change
      point can be very useful. First, it informs decision makers of the appropriate
      length of a test. Second, by removing the speeded responses, instead of the
      entire response sequence of an examinee suspected of speededness, ability
      estimation can be improved. Simulation studies show that this procedure is
      efficient in detecting both speeded examinees and the speeding point. Ability
      estimation is dramatically improved by removing speeded responses identified by
      our procedure. The procedure is then applied to a real dataset for illustration
      purpose.

PMID- 26305399
TI  - Regulatory crosstalk between type I and type II toxin-antitoxin systems in the
      human pathogen Enterococcus faecalis.
AB  - We discovered a chromosomal locus containing 2 toxin-antitoxin modules (TAs) with
      an antisense transcriptional organization in the E. faecalis clinical isolate
      V583. These TAs are homologous to the type I txpA-ratA system and the type II
      mazEF, respectively. We have shown that the putative MazF is toxic for E. coli
      and triggers RNA degradation, and its cognate antitoxin MazE counteracts
      toxicity. The second module, adjacent to mazEF, expresses a toxin predicted to
      belong to the TxpA type I family found in Firmicutes, and the antisense RNA
      antidote, RatA. Genomic analysis indicates that the cis-association of mazEF and
      txpA-ratA modules has been favored during evolution, suggesting a selective
      advantage for this TA organization in the E. faecalis species. We showed
      regulatory interplays between the 2 modules, involving transcription control and
      RNA stability. Remarkably, our data reveal that MazE and MazEF have a dual
      transcriptional activity: they act as autorepressors and activate ratA
      transcription, most likely in a direct manner. RatA controls txpA RNA levels
      through stability. Our data suggest a pivotal role of MazEF in the coordinated
      expression of mazEF and txpA-ratA modules in V583. To our knowledge, this is the
      first report describing a crosstalk between type I and II TAs. 

PMID- 26305402
TI  - Identifying knowledge activism in worker health and safety representation: A
      cluster analysis.
AB  - BACKGROUND: Although worker representation in OHS has been widely recognized as
      contributing to health and safety improvements at work, few studies have examined
      the role that worker representatives play in this process. Using a large
      quantitative sample, this paper seeks to confirm findings from an earlier
      exploratory qualitative study that worker representatives can be differentiated
      by the knowledge intensive tactics and strategies that they use to achieve
      changes in their workplace. METHODS: Just under 900 worker health and safety
      representatives in Ontario completed surveys which asked them to report on the
      amount of time they devoted to different types of representation activities
      (i.e., technical activities such as inspections and report writing vs. political
      activities such as mobilizing workers to build support), the kinds of conditions
      or hazards they tried to address through their representation (e.g., housekeeping
      vs. modifications in ventilation systems), and their reported success in making
      positive improvements. A cluster analysis was used to determine whether the
      worker representatives could be distinguished in terms of the relative time
      devoted to different activities and the clusters were then compared with
      reference to types of intervention efforts and outcomes. RESULTS: The cluster
      analysis identified three distinct groupings of representatives with significant
      differences in reported types of interventions and in their level of reported
      impact. Two of the clusters were consistent with the findings in the exploratory
      study, identified as knowledge activism for greater emphasis on knowledge based
      political activity and technical-legal representation for greater emphasis on
      formalized technical oriented procedures and legal regulations. Knowledge
      activists were more likely to take on challenging interventions and they reported
      more impact across the full range of interventions. CONCLUSIONS: This paper
      provides further support for the concepts of knowledge activism and technical
      legal representation when differentiating the strategic orientations and impact
      of worker health and safety representatives, with important implications for
      education, political support and recruitment.

PMID- 26305403
TI  - Zinc-catalyzed alkene cyclopropanation through zinc vinyl carbenoids generated
      from cyclopropenes.
AB  - The zinc-catalyzed reaction of cyclopropenes with alkenes leading to
      vinylcyclopropane derivatives is reported. A broad range of alkenes (including
      highly substituted or functionalized alkenes) is compatible with this protocol.
      On the basis of trapping experiments and computational studies, this
      cyclopropanation reaction is proposed to proceed through initial formation of an
      electrophilic zinc vinyl carbenoid intermediate, which may be involved in a
      concerted cyclopropanation reaction. The reported protocol represents an
      unprecedented and simple strategy for the catalytic generation of zinc vinyl
      carbenoids, which are promising intermediates in organic synthesis. 

PMID- 26305401
TI  - TMBIM6 (transmembrane BAX inhibitor motif containing 6) enhances autophagy and
      reduces renal dysfunction in a cyclosporine A-induced nephrotoxicity model.
AB  - Cyclosporine A (CsA) is widely used as an immunosuppressor in transplantation.
      Previous studies reported that CsA induces autophagy and that chronic treatment
      with CsA results in accumulation of autophagosomes and reduced autophagic
      clearance. Autophagy is a prosurvival process that promotes recovery from acute
      kidney injury by degrading misfolded proteins produced in the kidney. In the
      present study, we used TMBIM6-expressing HK-2, human kidney tubular cells (TMBIM6
      cells) and Tmbim6 knockout (tmbim6(-/-)) mice. When exposed to CsA, the TMBIM6
      cells maintained autophagy activity by preventing autophagosome accumulation.
      With regard to signaling, PRKKA/AMPK phosphorylation and mechanistic target of
      rapamycin (serine/threonine kinase) complex 1 (MTORC1) expression and its
      downstream target TFEB (transcription factor EB), a lysosome biogenesis factor,
      were regulated in the TMBIM6 cells. Lysosomal activity was highly increased or
      stably maintained in the presence of TMBIM6. In addition, treatment of tmbim6(-/
      ) mice with CsA resulted in increased autophagosome formation and decreased
      lysosome formation and activity. We also found that tmbim6(-/-) mice were
      susceptible to CsA-induced kidney injury. Taken together, these results indicate
      that TMBIM6 protects against CsA-induced nephrotoxicity both in vitro and in vivo
      by inducing autophagy and activating lysosomes. 

PMID- 26305404
TI  - Rational Control of Folding Cooperativity in DNA Quadruplexes.
AB  - Availability of basic tools for engineering molecular systems with precisely
      defined properties is crucial toward progress in development of new responsive
      materials. Among such materials are systems capable of generating an
      ultrasensitive response (i.e., large relative changes in output in response to
      small changes in input). Herein, we focus on a rational design of DNA quadruplex
      based structures as ultrasensitive response elements. In particular, we
      demonstrate how addition of allosteric guiding elements can be engineered into
      H(+)-responsive i-motif structure to yield maximized response sensitivity. 

PMID- 26305406
TI  - (+/-)-Acortatarinowins A-F, Norlignan, Neolignan, and Lignan Enantiomers from
      Acorus tatarinowii.
AB  - Three pairs of new 8-O-4'-type dinorneolignan enantiomers, (+/-)-acortatarinowins
      A-C (1a/1b-3a/3b), a pair of new 8-O-4'-type (4a/4b) and a pair of rare C7-C8'
      type (5a/5b) neolignan enantiomers, (+/-)-acortatarinowins D and E, and a pair of
      new furofuran-type lignan enantiomers, (+/-)-acortatarinowin F (6a/6b), along
      with two pairs of known lignan enantiomers (7a/7b and 8a/8b), were obtained from
      the rhizomes of Acorus tatarinowii. The separation of 1-8 by chiral HPLC using a
      Daicel IC column led to the isolation of eight pairs of enantiomers, 1a/1b-8a/8b,
      which had variable enantiomeric excess (ee) values of approximately 66, 71, 63,
      60, 0, 38, 48, and 75%, respectively. The structures were elucidated by extensive
      spectroscopic and chemical methods, and their absolute configurations were
      determined by a combined analysis of single-crystal X-ray diffraction and a
      modified Mosher's method, assisted by experimental and calculated electronic
      circular dichroism data. Among them, compounds 1a, 3a, 6b, 8a, and 8b showed weak
      inhibitory activities against NO production in activated macrophages with IC50
      values ranging from 23.3 to 38.0 MUM, respectively. 

PMID- 26305405
TI  - Chromosome Aberrations Determined by FISH in Radiation Workers from the
      Sellafield Nuclear Facility.
AB  - Workers from the Sellafield nuclear facility (Cumbria, UK) with occupational
      exposures to external sources of ionizing radiation were examined for
      translocation frequencies in peripheral blood lymphocytes using fluorescence in
      situ hybridization (FISH). This is an extension of an earlier study of retired
      workers, and includes analyses of additional samples from the earlier collection,
      bringing the total to 321. Another 164 samples from both current and retired
      employees, including 26 repeat samples, were obtained from a new collection, thus
      giving a combined dataset of 459 workers. This all-male population of workers was
      divided into 6 dose groups comprising 97 with recorded external occupational
      doses <50 mGy, 118 with 50-249 mGy, 129 with 250-499 mGy, 89 with 500-749 mGy, 17
      with 750-999 mGy and 9 with >1,000 mGy. Univariate analysis showed a significant
      association between external dose and translocation frequency (P < 0.001) with
      the estimate of slope +/- standard error being 1.174 +/- 0.164 * 10(-2)
      translocations per Gy. Multivariate analysis revealed that age increased the rate
      of translocations by 0.0229 +/- 0.0052 * 10(-2) per year (P < 0.001). However,
      the impact of age adjustment on the radiation dose response for translocation
      frequencies was minor with the new estimate of slope +/- standard error being
      1.163 +/- 0.162 * 10(-2) translocations per Gy. With the dose response for the
      induction of translocations by chronic in vivo low-LET radiation now well
      characterized, cytogenetic analysis can play an integral role in retrospective
      dose reconstruction of chronic exposure in epidemiological studies of exposed
      populations. 

PMID- 26305407
TI  - Umbilical cord blood markers of oxidative stress in pregnancies complicated by
      preterm prelabor rupture of membranes.
AB  - OBJECTIVE: To determine umbilical cord blood total antioxidant capacity (TAC),
      ferric reducing antioxidant power (FRAP), thiobarbituric acid-reacting substances
      (TBARS), advanced glycation end products (AGEs) and markers of oxidative stress
      in pregnancies complicated by preterm prelabor rupture of membranes (PPROM) and
      their associations with microbial invasion of the amniotic cavity (MIAC) and/or
      histological chorioamnionitis (HCA), funisitis and selected aspects of short-term
      neonatal morbidity. MATERIALS AND METHODS: One hundred and sixty-five women with
      singleton pregnancies complicated by PPROM were included in this study. Blood
      samples were obtained by venipuncture from the umbilical cord vein after the
      delivery of the newborn. The umbilical cord blood concentrations of TAC, FRAP,
      TBARS and AGEs were measured. RESULTS: The presence of MIAC, HCA and funisitis
      did not show differences in the umbilical cord blood TAC, FRAP, TBARS and AGEs
      concentrations. Positive correlations were found between the gestational age at
      sampling and umbilical cord blood TAC and AGEs concentrations (TAC: rho = 0.26; p
      = 0.001; AGEs: rho = 0.35; p < 0.0001). There was no association between
      umbilical cord blood TAC, FRAP, TBARS and AGEs concentrations and selected
      aspects of short-term neonatal morbidity. CONCLUSIONS: Oxidative stress is
      associated with PPROM, as indicated by the presence of markers tested in the
      umbilical cord blood; however, the evaluated oxidative stress markers are not
      influenced by the presence of MIAC and/or HCA, and funisitis or subsequent
      development of selected aspects of short-term neonatal morbidity.

PMID- 26305408
TI  - Targeting Glycoprotein NMB With Antibody-Drug Conjugate, Glembatumumab Vedotin,
      for the Treatment of Osteosarcoma.
AB  - BACKGROUND: Cure rates for children and young adults with osteosarcoma have
      remained stagnant over the past three decades. Targeting glycoprotein non
      metastatic b (GPNMB) with the antibody-drug conjugate glembatumumab vedotin has
      improved outcomes for patients with melanoma and breast cancer. The potential
      utility of targeting GPNMB in osteosarcoma was explored. METHODS: GPNMB protein
      expression was evaluated by immunohistochemistry in human osteosarcoma tumor
      samples and by enzyme-linked immunosorbent assay (ELISA) in osteosarcoma cell
      lines. mRNA expression was measured by quantitative PCR in primary osteosarcoma
      samples and cell lines. Surface GPNMB expression was evaluated by flow cytometry
      and correlated with in vitro and in vivo cytotoxicity of glembatumumab vedotin.
      RESULTS: Sixty seven human osteosarcoma samples were evaluated by
      immunohistochemistry, including 12 samples from initial biopsy, 38 samples from
      definitive surgery, and 17 from the time of disease recurrence. GPNMB was
      expressed in 92.5% (62/67) of osteosarcoma samples. All primary osteosarcoma
      samples expressed high levels of GPNMB mRNA. Glembatumumab induced cytotoxic
      effects in 74% (14/19) of osteosarcoma cell lines, and GPNMB protein levels
      correlated with glembatumumab in vitro cytotoxicity (r = -0.46, P = 0.04). All
      osteosarcoma cell lines demonstrated surface GPNMB expression. CONCLUSIONS: GPNMB
      is expressed in osteosarcoma and targeting GPNMB with the antibody-drug conjugate
      glembatumumab vedotin demonstrates osteosarcoma cytotoxic activity. Clinical
      trials are indicated to assess the efficacy of targeting GPNMB in patients with
      osteosarcoma.

PMID- 26305409
TI  - Genome-wide errant targeting by Hairy.
AB  - Metazoan transcriptional repressors regulate chromatin through diverse histone
      modifications. Contributions of individual factors to the chromatin landscape in
      development is difficult to establish, as global surveys reflect multiple changes
      in regulators. Therefore, we studied the conserved Hairy/Enhancer of Split family
      repressor Hairy, analyzing histone marks and gene expression in Drosophila
      embryos. This long-range repressor mediates histone acetylation and methylation
      in large blocks, with highly context-specific effects on target genes. Most
      strikingly, Hairy exhibits biochemical activity on many loci that are uncoupled
      to changes in gene expression. Rather than representing inert binding sites, as
      suggested for many eukaryotic factors, many regions are targeted errantly by
      Hairy to modify the chromatin landscape. Our findings emphasize that
      identification of active cis-regulatory elements must extend beyond the survey of
      prototypical chromatin marks. We speculate that this errant activity may provide
      a path for creation of new regulatory elements, facilitating the evolution of
      novel transcriptional circuits. 

PMID- 26305410
TI  - Cdc6 ATPase activity disengages Cdc6 from the pre-replicative complex to promote
      DNA replication.
AB  - To initiate DNA replication, cells first load an MCM helicase double hexamer at
      origins in a reaction requiring ORC, Cdc6, and Cdt1, also called pre-replicative
      complex (pre-RC) assembly. The essential mechanistic role of Cdc6 ATP hydrolysis
      in this reaction is still incompletely understood. Here, we show that although
      Cdc6 ATP hydrolysis is essential to initiate DNA replication, it is not essential
      for MCM loading. Using purified proteins, an ATPase-defective Cdc6 mutant 'Cdc6
      E224Q' promoted MCM loading on DNA. Cdc6-E224Q also promoted MCM binding at
      origins in vivo but cells remained blocked in G1-phase. If after loading MCM,
      Cdc6-E224Q was degraded, cells entered an apparently normal S-phase and
      replicated DNA, a phenotype seen with two additional Cdc6 ATPase-defective
      mutants. Cdc6 ATP hydrolysis is therefore required for Cdc6 disengagement from
      the pre-RC after helicase loading to advance subsequent steps in helicase
      activation in vivo. 

PMID- 26305412
TI  - The influence of the obstetrical condition on canine neonatal pulmonary
      functional competence.
AB  - OBJECTIVE: To compare the influence of the obstetrical condition on neonatal
      respiratory performance, to estimate surfactant synthesis through lecithin and
      sphingomyelin ratio (L/S) in amniotic fluid of pregnant bitches and correlate the
      L/S with the respiratory condition during the first hour of life. DESIGN:
      Prospective randomized study. SETTING: University veterinary teaching hospital
      and private referral centers. ANIMALS: In accordance to the condition at birth,
      puppies from 25 healthy bitches aged 2-6 years were allocated into: Eutocia Group
      -EUT (n = 19 neonates and 14 bitches); Dystocia Group--DYS (n = 8 neonates and 5
      bitches) and Elective Cesarean Section Group--CS (n = 12 neonates and 11
      bitches). INTERVENTIONS: Amniotic fluid was drawn from amniotic sac and lecithin
      (L) and sphingomyelin (S) were measured by high performance liquid chromatography
      to obtain the L/S ratio. Neonatal physical examination was performed at 1, 5, and
      60 minutes after delivery, and included the assessment of respiratory rate (RR)
      and respiration effort (RE). MEASUREMENTS AND MAIN RESULTS: CS group had
      significantly lower amniotic L/S ratio when compared to EUT and DYS. There were
      no significant differences between vaginal groups (EUT versus DYS) in respect to
      L/S ratios. RE of eutocic neonates improved promptly, while RE of DYS and CS
      groups improved only 1 hour following birth. Moreover, amniotic L/S ratio
      positively correlated with RR after 60 minutes. CONCLUSIONS: We identified a
      possible influence of the delivery method on the final surfactant maturation
      process. Thus, neonates born by elective CS prior to the onset of expulsive
      uterine contractions should have their respiratory parameters carefully
      monitored. Additionally, we propose that assessment of respiratory parameters 1
      hour following birth can serve as a practical means to indirectly estimate
      pulmonary maturation (ie, surfactant synthesis) in puppies.

PMID- 26305413
TI  - Nordic pole walking improves walking capacity in patients with intermittent
      claudication: a randomized controlled trial.
AB  - PURPOSE: The aim of the study was to compare the efficacy of Nordic pole walking
      (NPW) training with traditional treadmill training (TT) on a claudication (CD)
      and maximum walking distance (MWD) in patients with peripheral arterial disease
      (PAD). METHOD: Patients with intermittent claudication (IC) (n = 70; age=68.27)
      in the Fontaine class II were randomized into a two three-month rehabilitation
      programs performed three times per week. TT were finished by 31 patients, NPW by
      21. Walking capacity was measured by an exercise treadmill test (ETT) with the
      Gardner-Skinner protocol (before and after the program) and six minute walk test
      (6MWT) (before, during and after the program). RESULTS: In an ETT both groups
      reached significant increase in CD and MWD (p <= 0.005). In 6MWT NPW group
      reached significant increase in both CD (p = 0.001) and MWD (p = 0.001), whereas
      the TT group only in MWD (p = 0.001). CONCLUSIONS: NPW has been shown to be as
      effective as the standard TT and is much less expensive. It should be the
      preferred method of exercise for PAD patients with IC. IMPLICATIONS FOR
      REHABILITATION: Nordic walking training is a valuable form of rehabilitation for
      peripheral arterial disease (PAD) patients with intermittent claudication (IC).
      Nordic walking has been shown to be as efficient as traditional treadmill
      training. It is however more cost-effective method of rehabilitation in PAD
      patients.

PMID- 26305411
TI  - Effects of particle size and coating on toxicologic parameters, fecal elimination
      kinetics and tissue distribution of acutely ingested silver nanoparticles in a
      mouse model.
AB  - Consumer exposure to silver nanoparticles (AgNP) via ingestion can occur due to
      incorporation of AgNP into products such as food containers and dietary
      supplements. AgNP variations in size and coating may affect toxicity, elimination
      kinetics or tissue distribution. Here, we directly compared acute administration
      of AgNP of two differing coatings and sizes to mice, using doses of 0.1, 1 and 10
      mg/kg body weight/day administered by oral gavage for 3 days. The maximal dose is
      equivalent to 2000* the EPA oral reference dose. Silver acetate at the same doses
      was used as ionic silver control. We found no toxicity and no significant tissue
      accumulation. Additionally, no toxicity was seen when AgNP were dosed
      concurrently with a broad-spectrum antibiotic. Between 70.5% and 98.6% of the
      administered silver dose was recovered in feces and particle size and coating
      differences did not significantly influence fecal silver. Peak fecal silver was
      detected between 6- and 9-h post-administration and <0.5% of the administered
      dose was cumulatively detected in liver, spleen, intestines or urine at 48 h.
      Although particle size and coating did not affect tissue accumulation, silver was
      detected in liver, spleen and kidney of mice administered ionic silver at
      marginally higher levels than those administered AgNP, suggesting that silver ion
      may be more bioavailable. Our results suggest that, irrespective of particle size
      and coating, acute oral exposure to AgNP at doses relevant to potential human
      exposure is associated with predominantly fecal elimination and is not associated
      with accumulation in tissue or toxicity.

PMID- 26305414
TI  - Relevance between the Bulk Density and Li+-Ion Conductivity in a Porous
      Electrolyte: The Case of Li[Li1/3Ti5/3]O4.
AB  - The Li+-ion conductivity (sigmaLi) in an electrolyte is an important parameter
      with respect to the performance of all-solid-state lithium-ion batteries (LIBs).
      However, little is known about how sigmaLi in a porous electrolyte differs from
      that in a highly dense electrolyte. In this study, the relationship between the
      bulk density (dbulk) and apparent sigmaLi (sigmaLiapp) in a porous electrolyte of
      Li[Li1/3Ti5/3]O4 (LTO) was examined by theoretical and experimental approaches.
      The theoretical calculations demonstrated that dbulk and sigmaLi have a simple
      relationship irrespective of the radius of the spherical pores in the
      electrolyte; i.e., sigmaLi increases almost linearly with increasing zeta,where
      zeta is the ratio of d bulk to the theoretical density. In fact, the observed
      sigmaLiapp of LTO, which was determined by four-probe alternating-current
      impedance measurements, increased with increasing zeta. Hence, with this
      relationship, sigmaLiapp can be estimated by zeta and intrinsic sigmaLi
      (sigmaLiint) and vice versa; such estimations provide critical information for
      determining the optimum compositions of composite electrodes for all-solid-state
      LIBs. The temperature dependence of sigmaLiapp in LTO and differences between the
      calculated and experimental results are also discussed.

PMID- 26305415
TI  - Portable kit for identification and detection of drugs in human urine using
      surface-enhanced Raman spectroscopy.
AB  - A portable kit was demonstrated for rapid and reliable surface-enhanced Raman
      scattering (SERS) detection of drugs in human urine. This kit contains two sealed
      reagent tubes, a packet of standardized SERS substrates, and a mini Raman device.
      A 3 min pretreatment for separating amphetamines from human urine was developed
      with an extraction rate of >80% examined by ultraperformance liquid
      chromatography (UPLC). Simultaneously, highly reproducible two-dimensional (2D)
      gold nanorod (GNR) arrays were assembled by the use of
      methoxymercaptopoly(ethylene glycol) (mPEG-SH) capping. Thirty batches of GNR
      arrays produced the 1001 cm(-1) intensity of methamphetamine (MA) molecules with
      a relative standard deviation (RSD) of 7.9%, and a 21 * 21 MUm(2) area mapping on
      a 2D GNR array produced a statistical RSD of <10%, implying an excellent
      reproducibility and uniformity. The detection limit of amphetamines in human
      urine was at least 0.1 ppm. Moreover, the portable kit was successfully used for
      detecting MA, 3,4-methylenedioxymethamphetamine (MDMA), and methcathinone (MC) in
      30 volunteers' urine samples with various clinical natures, and the dual-analyte
      detection of MA and MDMA implied a good capability of multiplex analysis. UPLC
      examination and the SERS recovery test clearly indicated that our pretreatment
      procedure was sufficient to lower the high background signals caused by complex
      components in urine and demonstrated the practicability and the resistance to
      false positives, which is a vital problem for law enforcement applications. The
      excellent performance of our portable kit promises a great prospective toward a
      rapid, reliable, and on-spot analyzer, especially for public safety and
      healthcare. 

PMID- 26305416
TI  - Prediction of ROA and ECD Related to Conformational Changes of Astaxanthin
      Enantiomers.
AB  - ECD, ROA, and VCD were used to characterize astaxanthin conformers that differ in
      their arrangements of the beta-ionone ring in respect to the chain. We obtained
      ECD spectra experimentally, and the ECD, ROA, and VCD spectra of both individual
      conformers and conformation-averaged mixtures were predicted using quantum
      chemical calculations at the CAM-B3LYP level of theory using the PCM solvation
      model. The chiroptical methods employed (particularly ECD and ROA) were
      considerably more sensitive to conformational changes of astaxanthin compared to
      "mono-signed" conventional Raman spectroscopy. Strikingly, conformers that are
      the same optical isomers (e.g., of 3S,3'S-astxanthin), while geometrically nearly
      mirror images, exhibited sign-inversed ECD and ROA spectra. The conformational
      sensitivity of these chiroptical methods makes them a promising tool in the study
      of carotenoids in the natural environment (for instance, in de novo algal or
      yeast astaxanthin sources). 

PMID- 26305417
TI  - Interaction of ionic liquids with noble metal surfaces: structure formation and
      stability of [OMIM][TFSA] and [EMIM][TFSA] on Au(111) and Ag(111).
AB  - Aiming at a comprehensive understanding of the interaction of ionic liquids (ILs)
      with metal surfaces we have investigated the adsorption of two closely related
      ILs, 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide [EMIM][TFSA]
      and 1-methyl-3-octylimidazolium bis(trifluoromethylsulfonyl)imide [OMIM][TFSA],
      with two noble metal surfaces, Au(111) and Ag(111), under ultrahigh vacuum (UHV)
      conditions using scanning tunneling microscopy (STM). At room temperature, the
      ILs form a 2D liquid on either of the two surfaces, while at lower temperatures
      they condense into two-dimensional (2D) islands which exhibit ordered structures
      or a short-range ordered 2D glass structure. Comparison of the adlayer structures
      formed in the different adsorption systems and also with those determined
      recently for n-butyl-n-methylpyrrolidinium [TFSA](-) adlayers on Ag(111) and
      Au(111) (B. Uhl et al., Beilstein J. Nanotechnol., 2013, 4, 903) gains detailed
      insight into the adsorption geometry of the IL ions on the surface. The close
      similarity of the adlayer structures indicates that (i) the structure formation
      is dominated by the tendency to optimize the anion adsorption geometry, and that
      (ii) also in the present systems the cation adsorbs with the alkyl chain pointing
      up from the surface. 

PMID- 26305419
TI  - Allowable bias when monitoring reference change values.

PMID- 26305418
TI  - A compendium of DIS3 mutations and associated transcriptional signatures in
      plasma cell dyscrasias.
AB  - DIS3 is a catalytic subunit of the human exosome complex, containing
      exonucleolytic (RNB) and endonucleolytic (PIN) domains, recently found mutated in
      multiple myeloma (MM), a clinically and genetically heterogeneous form of plasma
      cell (PC) dyscrasia. We analyzed by next-generation sequencing (NGS) the DIS3 PIN
      and RNB domains in purified bone marrow PCs from 164 representative patients,
      including 130 cases with MM, 24 with primary PC leukemia and 10 with secondary PC
      leukemia. DIS3 mutations were found respectively in 18.5%, 25% and 30% of cases.
      Identified variants were predominantly missense mutations localized in the RNB
      domain, and were often detected at low allele frequency. DIS3 mutations were
      preferentially carried by IGH-translocated/nonhyperdiploid patients. Sequential
      analysis at diagnosis and relapse in a subset of cases highlighted some instances
      of increasing DIS3 mutation burden during disease progression. NGS also revealed
      that the majority of DIS3 variants in mutated cases were comparably detectable at
      transcriptional level. Furthermore, gene expression profiling analysis in DIS3
      mutated patients identified a transcriptional signature suggestive for impaired
      RNA exosome function. In conclusion, these data further support the pathological
      relevance of DIS3 mutations in plasma cell dyscrasias and suggest that DIS3 may
      represent a potential tumor suppressor gene in such disorders. 

PMID- 26305420
TI  - IL-4, IL-10 and high sensitivity-CRP as potential serum biomarkers of
      persistent/recurrent disease in papillary thyroid carcinoma with/without
      Hashimoto's thyroiditis.
AB  - OBJECTIVE: To investigate the potential role of interleukin 4 (IL-4), interleukin
      10 (IL-10) and high-sensitivity C-reactive protein (hs-CRP) as serum biomarkers
      of persistent/recurrent disease in papillary thyroid carcinoma (PTC) with/without
      Hashimoto's thyroiditis (HT). METHODS: Eighty consecutive patients (64 F/16 M,
      43.2 +/- 12.7 years) with PTC and 40 (37 F/3 M, 40.6 +/- 12.3 years) with
      papillary thyroid carcinoma associated with Hashimoto's thyroiditis (PTC + HT)
      were evaluated before radioiodine therapy. A control group of 20 patients with HT
      without thyroid cancer (18 F/2 M, 47.3 +/- 2.8 years) was included in the study
      for the comparison of cytokine levels. RESULTS: No meaningful differences were
      found in clinical outcomes between PTC and PTC + HT groups (47.5% vs. 45%
      persistent/recurrent disease). Serum IL-4, IL-10 and hs-CRP levels were higher in
      patients with persistent/recurrent disease compared to those without recurrence
      (p < 0.001). IL-4, IL-10 and hs-CRP were also found in substantially higher
      concentrations in PTC + HT patients with persistent/recurrent disease than in
      patients with HT or PTC (with or without recurrence) (p < 0.01). Positive
      correlations were observed between IL-4, IL-10, hs-CRP and thyroglobulin (Tg) (r
      between 0.48 and 0.56, p < 0.005) or antithyroglobulin antibodies (TgAb) (r
      between 0.63 and 0.80, p < 0.002) in PTC and PTC + HT patients with
      persistent/recurrent disease. CONCLUSIONS: Increased levels of serum IL-4, IL-10
      and hs-CRP are associated with persistent/recurrent disease in PTC and PTC + HT
      patients. Our results suggest that these biomarkers might be used to improve
      patient stratification according to the risk of recurrence, especially in
      patients with PTC + HT, where Tg levels are not reliable due to presence of TgAb.

PMID- 26305421
TI  - Standardizing serum 25-hydroxyvitamin D data from four Nordic population samples
      using the Vitamin D Standardization Program protocols: Shedding new light on
      vitamin D status in Nordic individuals.
AB  - Knowledge about the distributions of serum 25-hydroxyvitamin D (25(OH)D)
      concentrations in representative population samples is critical for the
      quantification of vitamin D deficiency as well as for setting dietary reference
      values and food-based strategies for its prevention. Such data for the European
      Union are of variable quality making it difficult to estimate the prevalence of
      vitamin D deficiency across member states. As a consequence of the widespread,
      method-related differences in measurements of serum 25(OH)D concentrations, the
      Vitamin D Standardization Program (VDSP) developed protocols for standardizing
      existing serum 25(OH)D data from national surveys around the world. The objective
      of the present work was to apply the VDSP protocols to existing serum 25(OH)D
      data from a Danish, a Norwegian, and a Finnish population-based health survey and
      from a Danish randomized controlled trial. A specifically-selected subset (n 100
      150) of bio-banked serum samples from each of the studies were reanalyzed for
      25(OH)D by LC-MS/MS and a calibration equation developed between old and new
      25(OH)D data, and this equation was applied to the entire data-sets from each
      study. Compared to estimates based on the original serum 25(OH)D data, the
      percentage vitamin D deficiency (< 30 nmol/L) decreased by 21.5% in the Danish
      health survey but by only 1.4% in the Norwegian health survey; but was relatively
      unchanged (0% and 0.2%) in the Finish survey or Danish RCT, respectively,
      following VDSP standardization. In conclusion, standardization of serum 25(OH)D
      concentrations is absolutely necessary in order to compare serum 25(OH)D
      concentrations across different study populations, which is needed to quantify
      and prevent vitamin D deficiency. 

PMID- 26305422
TI  - Hypo- and hypernatremia results in inaccurate erythrocyte mean corpuscular volume
      measurement in vitro, when using Sysmex XE 2100.
AB  - INTRODUCTION: Automated hematology analyzers dilute patient erythrocytes with an
      isoosmotic diluent before quantitating the erythrocyte mean cell volume (MCV).
      However, if patient plasma osmolality differs from the diluent, water will cross
      the erythrocytes membrane and establish a new equilibrium across the membrane.
      Since the new equilibrium is reached before the measurement of the MCV, the
      measured MCV may not reflect the true MCV in vivo. AIM: Calculation of the
      theoretical change in MCV at changed P-Sodium/P-Osmolality and to investigate if
      the automated blood cell counter Sysmex XE 2100 measures MCV correctly in hypo-
      and hyperosmolality and hypo-and hypernatremia. In addition, to examine whether
      the theoretically calculated change in MCV corresponds with the experimentally
      determined MCV change. METHOD: Theoretical calculation of the MCV inaccuracy at
      hypo- and hypernatremia, as well as at hypo- and hyperosmolality. Experimental
      studies with comparison of MCV measured at Sysmex XE 2100 to MCV found by using
      the manual measured packed cell volume method. RESULTS AND CONCLUSION:
      Measurement of MCV in hypo- and hypernatremia patients using the automated blood
      cell counter Sysmex XE 2100 resulted in inaccurate MCV. The experimental results
      also revealed a strong correlation between P-Osmolality/P-Sodium and MCV
      inaccuracy (R(2) = 0.70/0.85) similar to the theoretically calculated MCV
      inaccuracy. We suggest using mean cellular Hb (MCH) instead of MCV, mean
      corpuscular Hb concentration (MCHC) and B-Erythrocyte volume fraction (EVF).
      Alternatively, we suggest standardizing the measured MCV to a normal P-Sodium
      e.g. 140 mmol/L to estimate the in vivo MCV.

PMID- 26305423
TI  - NT-proBNP on Cobas h 232 in point-of-care testing: Performance in the primary
      health care versus in the hospital laboratory.
AB  - BACKGROUND: NT-proBNP may be useful for ruling out heart failure in primary
      health care. In this study we examined the analytical quality of NT-proBNP in
      primary health care on the Cobas h 232 point-of-care instrument compared with
      measurements performed in a hospital laboratory. MATERIALS AND METHODS: Blood
      samples requested for NT-proBNP were collected in primary health care (n = 95)
      and in a hospital laboratory (n = 107). NT-proBNP was measured on-site on Cobas h
      232 instruments both in primary health care centres and at the hospital
      laboratory and all samples were also analyzed with a comparison method at the
      hospital. Precision, trueness, accuracy, and lot-variation were determined at
      different concentration levels and evaluated according to acceptance criteria.
      Furthermore user-friendliness was assessed by questionnaires. RESULTS: For Cobas
      h 232 repeatability CV was 8.5-10.7% in the hospital setting and 5.3-10.0% in the
      primary health care and within the analytical quality specifications, but higher
      than with the comparison method (< 4%). NT-proBNP results obtained in primary
      health care were significantly higher than by the hospital comparison method
      (bias ranged from 14.3-23.7%), whereas there was no significant bias when Cobas h
      232 was used in the hospital setting (bias ranged from - 4.9 to 7.0%). User
      friendliness of Cobas h 232 was overall acceptable. CONCLUSION: Cobas h 232 point
      of-care instrument for measurement of NT-proBNP performed satisfactorily with
      regard to precision, user-friendliness, and lot-variation. A decrease in NT
      proBNP levels observed in samples transported to a central laboratory needs
      further attention and investigation.

PMID- 26305424
TI  - Hepatic radiofrequency ablation causes an increase of circulating histones in
      patients with hepatocellular carcinoma.
AB  - BACKGROUND: Radiofrequency ablation (RFA) has been increasingly accepted for the
      treatment of hepatocellular carcinoma (HCC). However, RFA has been associated
      with an obvious systemic inflammatory response, but little is known about the
      underlying mechanisms. Circulating histones are recently identified as pivotal
      inflammatory mediators. Hence, we investigated whether circulating histones are
      involved in RFA-related inflammation. METHODS: Serial blood samples were
      collected from 42 HCC patients undergoing RFA at 3 time points: pre-RFA, post-RFA
      (within 24 h), and in 4-week follow up after RFA. Plasma histones,
      myeloperoxidase (MPO), inflammatory cytokines (IL-1beta, IL-6, IL-10, TNF-alpha),
      liver damage parameters (ALT, AST), and creatinine were measured. RESULTS:
      Compared to pre-RFA (0.837 MUg/ml), there was a significant increase in the
      levels of circulating histones within 24 h post-RFA (4.576 MUg/ml, p < 0.0001);
      histones decreased to pre-RFA levels in 4-week follow up after RFA. Meanwhile,
      MPO, IL-6, and IL-10 were elevated remarkably within 24 h post-RFA, indicative of
      an occurrence of the inflammatory response. Notably, histone levels correlated
      well with MPO (r = 0.5678), IL-6 (r = 0.4851), and IL-10 (r = 0.3574),
      respectively. In addition, there was a significant damage of liver function in
      patients within 24 h post-RFA, evidenced by the increased levels of ALT and AST.
      No changes in creatinine levels were observed. CONCLUSIONS: These data
      demonstrate that circulating histones are excessively released in HCC patients
      treated with RFA, which may lead to systemic inflammation by stimulating
      neutrophil activation and promoting cytokine production. Circulating histones may
      act as a novel marker to indicate the extent of inflammation related to RFA.

PMID- 26305425
TI  - Confirmation of analytical performance characteristics required for the reference
      change value applied in patient monitoring.

PMID- 26305426
TI  - Allowable systematic difference between two instruments measuring the same
      analyte.

PMID- 26305427
TI  - Rebuttal to the PRO Statement.

PMID- 26305428
TI  - A sight on protein-based nanoparticles as drug/gene delivery systems.
AB  - Polymeric nanomaterials have extensively been applied for the preparation of
      targeted and controlled release drug/gene delivery systems. However, problems
      involved in the formulation of synthetic polymers such as using of the toxic
      solvents and surfactants have limited their desirable applications. In this
      regard, natural biomolecules including proteins and polysaccharide are suitable
      alternatives due to their safety. According to literature, protein-based
      nanoparticles possess many advantages for drug and gene delivery such as
      biocompatibility, biodegradability and ability to functionalize with targeting
      ligands. This review provides a general sight on the application of biodegradable
      protein-based nanoparticles in drug/gene delivery based on their origins. Their
      unique physicochemical properties that help them to be formulated as
      pharmaceutical carriers are also discussed. 

PMID- 26305429
TI  - High prevalence of antibiotic resistance in nasopharyngeal bacterial isolates
      from healthy children in rural Uganda: A cross-sectional study.
AB  - BACKGROUND: In Uganda, the main causes of death in children under 5 years of age
      are malaria and pneumonia--often due to delayed diagnosis and treatment. In
      preparation for a community case management intervention for pneumonia and
      malaria, the bacterial composition of the nasopharyngeal flora and its in vitro
      resistance were determined in children aged five or under to establish baseline
      resistance to commonly used antibiotics. METHODS: In a population-based survey in
      April 2008, nasopharyngeal specimens were collected from 152 randomly selected
      healthy children under 5 years of age in the Iganga/Mayuge Health and Demographic
      Surveillance Site (HDSS). Medical history and prior treatment were recorded.
      Demographic characteristics and risk factors for carriage of resistant strains
      were obtained from the HDSS census. Bacteria were isolated and analysed for
      antibiotic susceptibility using disk diffusion and E test. RESULTS: Streptococcus
      pneumoniae (S. pneumoniae) carriage was 58.6%, and, while most (80.9%) isolates
      had intermediate resistance to penicillin, none was highly resistant. Whereas no
      isolate was resistant to erythromycin, 98.9% were resistant to trimethoprim
      sulphamethoxazole (co-trimoxazole). CONCLUSIONS: In vitro resistance in S.
      pneumoniae to co-trimoxazole treatment was high, and the majority of isolates had
      intermediate resistance to penicillin. To inform treatment policies on the
      clinical efficacy of current treatment protocols for pneumonia in health
      facilities and at the community level, routine surveillance of resistance in
      pneumonia pathogens is needed as well as research on treatment efficacy in cases
      with resistant strains. Improved clinical algorithms and diagnostics for
      pneumonia should be developed.

PMID- 26305430
TI  - Release Kinetic in Yogurt from Gallic Acid Microparticles with Chemically
      Modified Inulin.
AB  - Gallic acid (GA) was encapsulated with native (NIn), cross-linked (CIn) and
      acetylated (AIn) inulin by spray-drying. Inulin microparticles were characterized
      by encapsulation efficiency (EE) and their release profile in yogurt. The EE was
      significantly higher for GA-CIn (98%) compared with GA-NIn (81%) and GA-AIn (77%)
      microparticles, showing the effect of the modification of inulin on interaction
      of GA-polymer. GA release profile data in yogurt for GA-CIn, GA-NIn and GA-AIn
      were fitted to Peppas and Higuchi models in order to obtain the GA release rate
      constant. Although the GA release rate constants were significantly different
      among systems, these differences were slight and the GA release was fast (80% < 2
      h) in the three systems, showing that inulin-systems did not control GA release
      in yogurt. The mechanism of GA release followed a Fickian diffusion and
      relaxation of chains for all microparticles. According to the release profile,
      these microparticles would be best suited for use in instant foods. 

PMID- 26305431
TI  - Voltage-dependent BK and Hv1 channels expressed in non-excitable tissues: New
      therapeutics opportunities as targets in human diseases.
AB  - Voltage-gated ion channels are the molecular determinants of cellular
      excitability. This group of ion channels is one of the most important
      pharmacological targets in excitable tissues such as nervous system, cardiac and
      skeletal muscle. Moreover, voltage-gated ion channels are expressed in non
      excitable cells, where they mediate key cellular functions through intracellular
      biochemical mechanisms rather than rapid electrical signaling. This review aims
      at illustrating the pharmacological impact of these ion channels, highlighting in
      particular the structural details and physiological functions of two of them -
      the high conductance voltage- and Ca(2+)-gated K(+) (BK) channels and voltage
      gated proton (Hv1) channels- in non-excitable cells. BK channels have been
      implicated in a variety of physiological processes ranging from regulation of
      smooth muscle tone to modulation of hormone and neurotransmitter release.
      Interestingly, BK channels are also involved in modulating K(+) transport in the
      mammalian kidney and colon epithelium with a potential role in the hyperkalemic
      phenotype observed in patients with familial hyperkalemic hypertension type 2,
      and in the pathophysiology of hypertension. In addition, BK channels are
      responsible for resting and stimulated Ca(2+)-activated K(+) secretion in the
      distal colon. Hv1 channels have been detected in many cell types, including
      macrophages, blood cells, lung epithelia, skeletal muscle and microglia. These
      channels have a central role in the phagocytic system. In macrophages, Hv1
      channels participate in the generation of reactive oxygen species in the
      respiratory burst during the process of phagocytosis. 

PMID- 26305432
TI  - Fyn is an important molecule in cancer pathogenesis and drug resistance.
AB  - Fyn is a non-receptor tyrosine kinase that belongs to the Src family kinases
      (SFKs) which under normal physiological conditions is involved in signal
      transduction pathways in the nervous system, as well as the development and
      activation of T lymphocytes. In cancer, Fyn contributes to the development and
      progression of several cancer types through its involvement in the control of
      cell growth, death, morphogenic transformation and cellular motility. Enhanced
      expression and/or activation of Fyn is observed in various cancers, including
      melanoma, glioblastoma, squamous cell carcinoma, prostate and breast cancers.
      Recent studies have demonstrated the importance of Fyn in the resistance or
      susceptibility of cancer cells to some anti-cancer treatments. We have recently
      shown that Fyn is upregulated in tamoxifen-resistant breast cancer cell lines and
      demonstrated that it plays a key role in the resistance mechanism. Further, we
      found that the cellular localization of Fyn within cancer cells of primary ER+
      breast tumor tissue may serve as a prognostic marker. Understanding the role of
      Fyn in initiation and progression of cancer and its contribution to resistance
      against anti-cancer therapeutic agents may facilitate the development and use of
      novel drugs targeting Fyn for better management of malignancies. 

PMID- 26305433
TI  - Current Approaches to the Management of Peripheral Neuropathic Pain.
AB  - Symptoms and signs of neuropathic pain can be both positive and negative.
      Tricyclic antidepressants are the first-line treatment option for neuropathic
      pain. Opioid agonists have demonstrated efficacy in patients with neuropathic
      pain. Combination therapy in the management of neuropathic pain is not well
      researched.-- This report is adapted from paineurope 2015: Issue 1, (c)Haymarket
      Medical Publications Ltd., and is presented with permission. paineurope is
      provided as a service to pain management by Mundipharma International, Ltd., and
      is distributed free of charge to health care professionals in Europe. Archival
      issues can be viewed via the Web site: www.paineurope.com , at which health
      professionals can find links to the original articles and request copies of the
      quarterly publication and access additional pain education and pain management
      resources.

PMID- 26305434
TI  - Modulated Degradation of Transient Electronic Devices through Multilayer Silk
      Fibroin Pockets.
AB  - The recent introduction of transient, bioresorbable electronics into the field of
      electronic device design offers promise for the areas of medical implants and
      environmental monitors, where programmed loss of function and environmental
      resorption are advantageous characteristics. Materials challenges remain,
      however, in protecting the labile device components from degradation at faster
      than desirable rates. Here we introduce an indirect passivation strategy for
      transient electronic devices that consists of encapsulation in multiple air
      pockets fabricated from silk fibroin. This approach is investigated through the
      properties of silk as a diffusional barrier to water penetration, coupled with
      the degradation of magnesium-based devices in humid air. Finally, silk pockets
      are demonstrated to be useful for controlled modulation of device lifetime. This
      approach may provide additional future opportunities for silk utility due to the
      low immunogenicity of the material and its ability to stabilize labile
      biotherapeutic dopants. 

PMID- 26305435
TI  - Is Pornography Really about "Making Hate to Women"? Pornography Users Hold More
      Gender Egalitarian Attitudes Than Nonusers in a Representative American Sample.
AB  - According to radical feminist theory, pornography serves to further the
      subordination of women by training its users, males and females alike, to view
      women as little more than sex objects over whom men should have complete control.
      Composite variables from the General Social Survey were used to test the
      hypothesis that pornography users would hold attitudes that were more supportive
      of gender nonegalitarianism than nonusers of pornography. Results did not support
      hypotheses derived from radical feminist theory. Pornography users held more
      egalitarian attitudes--toward women in positions of power, toward women working
      outside the home, and toward abortion--than nonusers of pornography. Further,
      pornography users and pornography nonusers did not differ significantly in their
      attitudes toward the traditional family and in their self-identification as
      feminist. The results of this study suggest that pornography use may not be
      associated with gender nonegalitarian attitudes in a manner that is consistent
      with radical feminist theory.

PMID- 26305436
TI  - Issue Highlights - Cytometry Part B November 2013.

PMID- 26305437
TI  - Compilation of a preliminary checklist for the differential diagnosis of
      neurogenic stuttering.
AB  - BACKGROUND: Neurogenic stuttering (NS) is the most frequently occurring acquired
      form of stuttering in children and adults. This form of stuttering is primarily
      caused by neurological incidents. Owing to controversies with regard to
      similarities between developmental stuttering (DS) and NS symptomatology,
      differential diagnosis is problematic. Differential diagnosis will guide the
      appropriate management of persons who stutter (PWS). OBJECTIVES: The aim of this
      study was to describe and highlight the characteristics of NS in order to compile
      a preliminary checklist for accurate diagnosis and intervention. METHOD: An
      explorative, applied mixed method, multiple case study research design was
      followed. Purposive sampling was used to select four participants. A
      comprehensive assessment battery was compiled for data collection. RESULTS: The
      results revealed a distinct pattern of core stuttering behaviours in NS, although
      discrepancies existed regarding stuttering severity and frequency. It was also
      found that DS and NS can co-occur. The case history and the core stuttering
      pattern are important considerations during differential diagnosis, as these are
      the only consistent characteristics in people with NS. CONCLUSION: It is unlikely
      that all the symptoms of NS are present in an individual. The researchers
      scrutinised the findings of this study and the findings of previous literature to
      compile a potentially workable checklist.

PMID- 26305438
TI  - Availability of audiological equipment and protocols for paediatric assessment
      and hearing aid fitting in Gauteng, South Africa.
AB  - BACKGROUND: Accurate diagnosis and management of hearing loss (HL) is based on
      valid and accurate ear-specific and frequency-specific information. This is
      especially relevant as non-optimal hearing amplification as part of early hearing
      detection and intervention programmes may result in further delays in the speech
      and language development of children with HL. Audiological measures utilised may
      vary according to the age, cognitive ability and physical ability of the infant
      or child. It is therefore important to compare and critically evaluate current
      clinical practice in order to recommend guidelines for paediatric audiology in
      South Africa. OBJECTIVES: To determine the availability of audiological equipment
      and clinical protocols used by audiologists in Gauteng for paediatric
      audiological assessment and hearing aid (HA) fitting. METHOD: A descriptive,
      cross-sectional survey research design was utilised to describe the availability
      of clinical audiological equipment and protocols used by audiologists in Gauteng,
      South Africa for paediatric assessment and HA fitting. Eighteen audiology
      departments, eleven public hospitals and seven private practices were included in
      the study. RESULTS: Results revealed the limited availability of departmental
      protocols within departments for paediatric assessment and HA fitting. Although
      there appeared to be a wide variety of equipment available to audiologists in
      public sector hospitals and private practice, a lack of high-frequency
      tympanometers and equipment for real ear measurements was revealed. CONCLUSION:
      These findings highlight the need for the development and use of current,
      evidence-based practice guidelines for paediatric audiological assessment and HA
      fitting in South Africa. These guidelines should include a list of essential
      equipment required for paediatric assessment and HA fitting. Current, evidence
      based practice guidelines for paediatric HA fitting are important in ensuring
      that secondary developmental delays associated with a delay in early intervention
      for children with HL are reduced.

PMID- 26305439
TI  - The impact of tinnitus on daily activities in adult tinnitus sufferers: A pilot
      study.
AB  - BACKGROUND: Few South African studies have been published on the impact of
      tinnitus on quality of life of tinnitus sufferers, although evidence suggests
      that a large portion of the general population suffers from tinnitus. OBJECTIVES:
      The current study aimed at describing the effects of tinnitus on the quality of
      life of the participants as measured by the Tinnitus Handicap Inventory (THI).
      METHOD: In a cross-sectional descriptive study design, 27 participants took part
      in the study by completing a self-administered THI questionnaire and
      participating in a semi-structured interview. Descriptive and inferential
      statistics were used to analyse the data. Descriptively, content analysis was
      used to organise and convey results from the interviews. RESULTS: Participants
      reported a wide range of perceived disability on the THI. Results ranged from
      mild to catastrophic, with functional disability being most prominent in all
      participants, although there were differences when results were analysed
      according to gender. There was an association between gender and the type of
      perceived disability, although this was statistically non-significant (p > 0.05).
      Only 26% of the participants reported no effect on occupational performance and
      quality of life, with the remainder of the participants reporting a significant
      effect. Limited effective management strategies were reported to have been
      implemented - a significant implication for the audiologists. CONCLUSION: The
      results have implications for audiologists as they suggest that audiologists
      should take a detailed case history to determine the extent to which tinnitus
      affects the individual. Furthermore, audiologists should administer a scale such
      as the THI in the management of tinnitus.

PMID- 26305440
TI  - National survey of paediatric audiological services for diagnosis and
      intervention in the South African private health care sector.
AB  - OBJECTIVE: A national survey of early hearing detection and intervention services
      was undertaken to describe the current status of diagnostic and intervention
      services in the South African private health care sector. METHODS: All private
      hospitals with obstetric units (n = 166) were surveyed telephonically. The data
      was integrated with data collected from self-administered questionnaires
      subsequently distributed nationally to private audiology practices providing
      hearing screening at the respective hospitals reporting hearing screening
      services (n = 87). Data was analysed descriptively to yield national percentages
      and frequency distributions. RESULTS: Average reported age at diagnosis was 11
      months. Most participants (74%) indicated that less than 20% of infants fitted
      with hearing aids received amplification before the age of 6 months. Most (64%)
      participants indicated that the average period between confirmed diagnosis and
      hearing aid fitting was 1 month, on par with international benchmarks. Only 16%
      23% of participants included all diagnostic procedures recommended by the Health
      Professions Council of South Africa's 2007 position statement for minimum
      diagnostic test batteries for infants and young children. CONCLUSIONS: Diagnosis
      of hearing loss, hearing aid fitting and audiological intervention is delayed
      significantly in the South African private health care sector. Improved services
      should include integrated systematic hospital-based screening as part of birthing
      packages with diagnostic referral to specialist paediatric audiologists for
      accurate assessment and management of patients in a timely manner.

PMID- 26305441
TI  - Infection prevention and control measures currently applied in South African
      audiology.
AB  - BACKGROUND: To counter the global increase in infection-related deaths, infection
      control has recently developed into an active area of research. Many diseases can
      be prevented by infection control. In the confines of the audiology clinic, cross
      contamination by micro-organisms associated with opportunistic infections remains
      a real concern. OBJECTIVE: The primary aim of the study was to ascertain the
      methods that audiologists in South Africa use to prevent and control the spread
      of infections during and after consultation with clients. METHOD: A survey study
      was conducted, using a self-administered questionnaire. Fifty currently
      practising audiologists participated in the study. RESULTS: The majority (84%; n
      = 42) of respondents acknowledged the importance of hand hygiene for the purpose
      of infection control, with 76% (n = 38) making use of no-rinse hand sanitisers.
      Approximately a third of audiologists wear gloves during procedures such as
      otoscopy and immittance, and while handling hearing aids. Disinfecting
      audiological equipment seem to be the preferred choice of infection control, with
      only 60% (n = 30) of respondents sterilising audiological equipment after each
      individual patient consultation. Less than half of the respondents disinfected
      touch surfaces and toys in the reception area. CONCLUSIONS: Based on the results,
      further education and training should focus on measures implemented in infection
      control, awareness of possible risk factors at work settings, and vaccination as
      an effective means of infection control.

PMID- 26305442
TI  - Classroom intervention to change peers' attitudes towards children who stutter: A
      feasibility study.
AB  - BACKGROUND: Before interventions are implemented, the potential treatment benefit
      must be determined. OBJECTIVES: The primary objective of this feasibility study
      was to assess if peers' attitudes towards children who stutter (CWS) change one
      month after the administration of the Classroom Communication Resource (CCR). The
      secondary objectives of the study were to determine if differences in peer
      attitudes were related to gender and to previous exposure to a person who
      stutters. METHOD: The study used a cluster randomised control trial design. The
      study included 211 Grade 7 participants from schools in the Cape Town Metropole.
      The CCR intervention was administered to 97 participants in the experimental
      group, whilst 114 participants in the control group did not receive the
      intervention. The Stuttering Resource Outcome Measure(SROM) used as the outcome
      measure during pre- and post-test period. STATISTICA was used for in-depth data
      analysis. RESULTS: An overall positive direction of change in scores was observed
      for the experimental group compared with the control group. However, the
      magnitude of change in the experimental group was not statistically significant
      (p = 0.2683). Male and female participants did not differ significantly in their
      scores on the SROM across pre-test and post-test periods. Participants who had
      exposure to individuals who stutter had significantly more positive scores on the
      SROM in the pre-test and post-test periods compared to those who had no direct
      exposure to stuttering. CONCLUSION: This result indicated the beginning of
      positive attitude change which may be attributed to the intervention. Further
      investigation is warranted.

PMID- 26305443
TI  - Hearing screening procedures and protocols in use at immunisation clinics in
      South Africa.
AB  - BACKGROUND: There exists a need for context-relevant research aimed at
      facilitating the efficacious provision of early hearing detection and
      intervention services in South Africa. OBJECTIVES: This study aimed to determine
      the hearing screening procedures and protocols as well as referral protocols in
      use at maternal child woman's health (MCWH) immunisation clinics in South Africa.
      METHOD: Thirty primary health care immunisation clinic managers or acting
      managers were interviewed in two South African sample groups. An exploratory, non
      experimental,qualitative research design was employed incorporating both
      quantitative and qualitative information. An interview using a questionnaire was
      administered with all participants. The questionnaire encompassed areas such as
      work contexts, hearing screening contexts and information management systems, as
      well as quality control measures in place at these clinics.Content analysis was
      then used to code emergent themes into specific categories. Frequency
      calculations of these themes were calculated and results described qualitatively.
      RESULTS: No primary health care (PHC) clinics placed within the identified sites
      provided formalised new-born/infant hearing screening and none of these
      facilities had equipment to do so. Most sites attributed the lack of formalised
      hearing screening to budgetary and human resource issues, staff training in
      particular. Non-formalised hearing screening protocols in place demonstrated
      inconsistencies in application across districts and none complied with Health
      Professions Council of South Africa (HPCSA) clinic guidelines or any
      international guidelines. CONCLUSION: Results from the current study have
      assisted in identifying procedural and logistical assets and barriers to
      implementation of HPCSA clinic guidelines for early hearing detection and
      intervention (EHDI) at immunisation clinics in South Africa.

PMID- 26305444
TI  - Idiosyncratic sound systems of the South African Bantu languages: Research and
      clinical implications for speech-language pathologists and audiologists.
AB  - The objective of this article is to create awareness amongst speech-language
      pathologists and audiologists in South Africa regarding the difference between
      the sound systems of Germanic languages and the sound systems of South African
      Bantu languages. A brief overview of the sound systems of two Bantu languages,
      namely isiZulu and Setswana, is provided. These two languages are representative
      of the Nguni language group and the Sotho group respectively.Consideration is
      given to the notion of language-specific symptoms of speech, language and hearing
      disorders in addition to universal symptoms. The possible impact of speech
      production, language and hearing disorders on the ability to produce and perceive
      speech in these languages, and the challenges that this holds for research and
      clinical practice, are pointed out.

PMID- 26305448
TI  - Could be the predominantly-used hemibody related to the weight bearing
      distribution modified by the chronic hemiparesis after stroke?
AB  - Since the first Broca publications issued from 1970s, lateralized functions in
      the human brain have urged the researchers to postulate hypothesis based in the
      right-left asymmetries and, according to some theories, the lateralization of the
      voluntary motor control could represent a solution to avoid redundant process
      optimizing space and time. Supported by this idea, the clinicians and researchers
      tend to concept that the chronic hemiplegic stroke patients learn to use
      predominantly the non-affected hemibody after stroke in which is more convenient
      to execute their daily life activities, modifying their natural preference in
      some cases. Although could seems reasonable conceptualize the non-affected side
      as the predominantly-used hemibody for motor tasks after stroke (convenience
      hypothesis), evidences point to exist also hemiplegic patients that developed a
      predominantly use of the affected side. To float an idea, in terms of weight
      bearing distribution during upright position, the researchers have found patients
      overloading the non-affected hemibody, as expected; but also patients overloading
      the affected hemibody, not presenting necessarily Pusher's syndrome cases. Given
      the evidences, we could propose a severity-modulated predominance hypothesis
      which complements the convenience hypothesis. According to our complementary
      hypothesis, the severity of the motor disability presented in the hemiparesis
      condition (light, moderate and heavy severity) could determine a predominant use
      defined by preference (light to moderate severity) or convenience (moderate to
      heavy severity). In this hypothesis, we postulate ideas from a rehabilitation
      perspective to be incorporated in treatment programs.

PMID- 26305447
TI  - A natural therapeutic approach for the treatment of periodontitis by MK615.
AB  - Periodontitis is a chronic inflammatory disease that affects the tooth-supporting
      tissues. Gingival fibroblasts are the most abundant cells in periodontal tissues
      and they participate actively in the host inflammatory response to periodontal
      pathogens that is known to mediate local tissue destruction in periodontitis. The
      Japanese apricot, known as Ume in Japanese, has been a traditional Japanese
      medicine for centuries and is a familiar and commonly consumed food. The health
      benefits of Ume are widely recognized and have been confirmed in recent studies
      showing that MK615, an extract of compounds from Ume, has strong anticancer and
      anti-inflammatory effects. However, the potential role of MK615 in oral health is
      unknown. We hypothesized that the anti-inflammatory activities of MK615 could be
      exploited to inhibit the effects of lipopolysaccharide (LPS) produced by
      periodontal bacterial pathogens, such as Aggregatibacter actinomycetemcomitans
      and Porphyromonas gingivalis. Here, we show that LPS-induced interleukin (IL)-6
      and IL-8 production by gingival fibroblasts was dose-dependently inhibited by
      MK615. As a potent inhibitor of the inflammatory responses induced by periodontal
      pathogens, MK615 merits further testing as a therapeutic agent in inflammatory
      diseases such as periodontitis.

PMID- 26305446
TI  - Enzyme-Responsive Nanoparticles for Targeted Accumulation and Prolonged Retention
      in Heart Tissue after Myocardial Infarction.
AB  - A method for targeting to and retaining intravenously injected nanoparticles at
      the site of acute myocardial infarction in a rat model is described. Enzyme
      responsive peptide-polymer amphiphiles are assembled as spherical micellar
      nanoparticles, and undergo a morphological transition from spherical-shaped,
      discrete materials to network-like assemblies when acted upon by matrix
      metalloproteinases (MMP-2 and MMP-9), which are up-regulated in heart tissue post
      myocardial infarction. 

PMID- 26305449
TI  - Family history of venous thromboembolism as a risk factor and genetic research
      tool.
AB  - Familial clustering of venous thromboembolism (VTE) was described as far back as
      1905 by Briggs. Although Egeberg discovered inherited deficiency of antithrombin
      in 1965, it was not until Dahlback discovered resistance to activated protein C
      in 1993 that it became clear that genetic factors are common risk factors of VTE.
      Several genes have been linked to familial aggregation of VTE and genome-wide
      association studies have found several novel gene loci. Still, it has been
      estimated that much of the heritability for VTE remains to be discovered. Family
      history (FH) of VTE is therefore still important to determine whether a patient
      has an increased genetic risk of VTE. FH has the potential to represent the sum
      of effects and interactions between environmental and genetic factors. In this
      article the design, methodology, results, clinical and genetic implications of FH
      studies of VTE are reviewed. FH in first-degree relatives (siblings and/or
      parents) is associated with a 2-3 times increased familial relative risk (FRR).
      However, the FRR is dependent on age, number of affected relatives, and
      presentation of VTE (provoked/unprovoked). Especially high familial risks are
      observed in individuals with two or more affected siblings (FFR> 50). However,
      the familial risk for recurrent VTE is much lower or non-significant. Moreover,
      FH of VTE appears mainly to be important for venous diseases (i. e. VTE and
      varicose veins). The familial associations with other diseases are weaker. In
      conclusion, FH of VTE is an important research tool and a clinically potential
      useful risk factor for VTE. 

PMID- 26305450
TI  - Logarithmic intensity compression in fluorescence guided surgery applications.
AB  - The use of fluorescence video imaging to guide surgery is rapidly expanding, and
      improvements in camera readout dynamic range have not matched display
      capabilities. Logarithmic intensity compression is a fast, single-step mapping
      technique that can map the useable dynamic range of high-bit fluorescence images
      onto the typical 8-bit display and potentially be a variable dynamic contrast
      enhancement tool. We demonstrate a ~4.6  times improvement in image quality
      quantified by image entropy and a dynamic range reduction by a factor of ~380 by
      the use of log-compression tools in processing in vivo fluorescence images.

PMID- 26305452
TI  - Jewish Law, Scarcity of Sperm Donors and the Consequent Private Import of Sperm
      of Non-Jews by Israeli Women.
AB  - AIM: The objective of this article is to explore how Israeli Jewish women cope
      with the religious prohibition on sperm donation and the scarcity of Israeli
      donors, and to estimate the number of available sperm donors in Israel. METHODS:
      A key word search was employed to retrieve relevant Hebrew and English sources;
      additional information was collected via interviews with two sperm donors and
      twelve donor insemination patients. RESULTS: Rabbinical instructions focus on
      married women and refrain from acknowledging the growing number of non-married
      donor insemination patients. Non-married women follow the restrictions relevant
      to married women and hence refrain from purchasing Jewish sperm. Israeli sperm
      banks offer donations of Jewish donors whose number is estimated at a maximum of
      140 and a minimum of 50 for the entire Jewish population of 6.2 million. In order
      to abide by American Society for Reproductive Medicine recommendations, the
      number of available donors should optimally be six times larger. The scarcity of
      sperm donors drives the private import of American sperm donations. CONCLUSION:
      Reconsideration of the rabbinical prohibition to allow collecting sperm for
      donating to women who wish to have a baby is needed for the sake of increasing
      the donor pool, along with measures to ensure donors' privacy and dignity. (c)
      2015 S. Karger AG, Basel.

PMID- 26305451
TI  - Suicide and accidental deaths among patients with non-metastatic prostate cancer.
AB  - OBJECTIVE: To determine if American men with prostate cancer are at increased
      risk of suicide/accidental death compared with other cancers and if the receipt
      of definitive treatment alters this association, as patients with cancer are at
      increased risk of suicide and evidence suggests a relationship between suicides
      and deaths due to accidents and externally caused injuries. PATIENTS AND METHODS:
      Demographic, socio-economic and tumour characteristics of men with prostate
      cancer and men with other solid malignancies were extracted from the
      Surveillance, Epidemiology and End Results (SEER) database (1988-2010). Poisson
      regression models were fitted to compare the incidence of suicidal and accidental
      deaths in prostate cancer vs other solid cancers. Multivariate Cox regression was
      used to determine if receipt of definitive primary treatment impacted the risk of
      suicide or accidental death in men with localised/regional prostate cancer.
      RESULTS: Risk of suicidal and accidental death was significantly lower in men
      with prostate cancer (1 165 [0.2%] and 3 199 [0.6%]) than men with other cancers
      (2 232 [0.2%] and 4 501 [0.5%], respectively), except within the first year of
      diagnosis (adjusted relative risk [ARR] 3.98, 95% confidence interval [CI] 3.02
      5.23 and ARR 4.22, 95% CI 3.24-5.51, respectively, 0-3 months after diagnosis).
      Men with non-metastatic prostate cancer who were White, uninsured, or recommended
      but did not receive treatment (hazard ratio vs treated 1.44, 95% CI 1.20-1.72,
      and 1.44, 95% CI 1.30-1.59, both P < 0.001) were at increased risk of suicidal
      and accidental mortality, respectively. Absence of data about previous co
      morbidities and drug addictions in the SEER dataset was an important limitation.
      CONCLUSIONS: Relative to other cancers, men with prostate cancer were at
      increased risk of suicide and accidental deaths within the first year of
      diagnosis and when definitive treatment was recommended but not received,
      suggesting the need for close monitoring and coordination with mental health
      professionals in at-risk men with potentially curable disease.

PMID- 26305453
TI  - The colonic mucus protection depends on the microbiota.
AB  - The intestinal mucus is a pivotal part of our intestinal protection. It provides
      slow diffusion of protective molecules, trapping of luminal material as bacteria
      and smooth transport in the small intestine. In colon it restricts bacterial
      access to the epithelium limiting the responses to the enormous bacterial load
      present at this location. The development of these systems depends on the
      microbiota composition as seen in our recent study comparing the mucus phenotype
      in 2 colonies kept in different husbandries within the same SPF animal facility.
      One colony had impenetrable colonic mucus while the other colony had more
      penetrable mucus. The mucus phenotypes were transmitted via the microbiota and
      clear differences in its composition could be detected. Candidates associated
      with the different colonies were identified but the observed mucus difference
      could not be assigned to a specific bacterium. 

PMID- 26305454
TI  - Impact of refractive index mismatches on coherent anti-Stokes Raman scattering
      and multiphoton autofluorescence tomography of human skin in vivo.
AB  - Optical non-linear multimodal tomography is a powerful diagnostic imaging tool to
      analyse human skin based on its autofluorescence and second-harmonic generation
      signals. Recently, the field of clinical non-linear imaging has been extended by
      adding coherent anti-Stokes Raman scattering (CARS)-a further optical sectioning
      method for the detection of non-fluorescent molecules. However, the heterogeneity
      of refractive indices of different substances in complex tissues like human skin
      can have a strong influence on CARS image formation and requires careful clinical
      interpretation of the detected signals. Interestingly, very regular patterns are
      present in the CARS images, which have no correspondence to the morphology
      revealed by autofluorescence at the same depth. The purpose of this paper is to
      clarify this phenomenon and to sensitize users for possible artefacts. A further
      part of this paper is the detailed comparison of CARS and autofluorescence images
      of healthy human skin in vivo covering the complete epidermis and part of the
      upper dermis by employing the flexible medical non-linear tomograph MPTflex CARS.

PMID- 26305455
TI  - Prostate Tumor Overexpressed 1 (PTOV1) Is a Novel Prognostic Marker for
      Nasopharyngeal Carcinoma Progression and Poor Survival Outcomes.
AB  - BACKGROUND: Prostate tumor overexpressed 1 (PTOV1) has been reported to
      contribute to increased cancer proliferation. However, the clinical significance
      of PTOV1 in the development and progression of nasopharyngeal carcinoma (NPC) is
      unclear. Our study aimed to investigate the expression pattern of PTOV1 in NPC
      and its correlation with clinicopathological features of patients. METHODS:
      Western blotting and real-time PCR were conducted to examine PTOV1 expression
      levels in NPC cell lines and biopsy tissues compared with normal controls.
      Immunohistochemistry (IHC) was performed to analyze PTOV1 protein expression in
      paraffin-embedded tissues from 123 patients. Statistical analyses were applied to
      evaluate the clinical significance of PTOV1 expression. RESULTS: PTOV1 mRNA and
      protein levels were upregulated in NPC cell lines and clinical samples. IHC
      analyses showed that PTOV1 was highly expressed in 68 (55.3%) of 123 NPC
      specimens. Statistical analysis revealed that PTOV1 expression was significantly
      correlated with clinical stage (P < 0.001), T classification (P = 0.042) and N
      classification (P = 0.001). Patients with a higher PTOV1 expression had shorter
      overall survival compared with those with a lower PTOV1 expression level,
      especially in lower N stage patients. Multivariate analyses suggested that PTOV1
      expression was an independent prognostic marker for survival in NPC patients.
      CONCLUSIONS: Our data demonstrated that PTOV1 overexpression is associated with
      poor survival outcomes of NPC patients, especially in N0-1 patients. Hence, PTOV1
      may help to detect early lymph node metastasis of NPC patients and serve as an
      independent prognostic biomarker for human NPC.

PMID- 26305456
TI  - CRP-Mediated Carbon Catabolite Regulation of Yersinia pestis Biofilm Formation Is
      Enhanced by the Carbon Storage Regulator Protein, CsrA.
AB  - The natural transmission of Yersinia pestis is reliant upon biofilm blockage of
      the flea vector. However, the environmentally-responsive adaptive regulators
      which facilitate Y. pestis biofilm production in accordance with the flea midgut
      milieu are not well understood. We seek to establish the impact of available
      carbon source metabolism and storage upon Y. pestis biofilm production. Our
      findings demonstrate that Y. pestis biofilm production is subject to carbon
      catabolite regulation in which the presence of glucose impairs biofilm
      production; whereas, the sole metabolism of alternate carbon sources promotes
      robust biofilm formation. This observation is facilitated by the cAMP receptor
      protein, CRP. In accordance with a stark growth defect, deletion of crp in both
      CO92 and KIM6+ Y. pestis strains significantly impaired biofilm production when
      solely utilizing alternate carbon sources. Media supplementation with cAMP, a
      small-molecule activator of CRP, did not significantly alter Y. pestis biofilm
      production. Furthermore, CRP did not alter mRNA abundance of previously
      characterized hms biofilm synthesis and regulation factors. Therefore, our
      findings indicate CRP does not confer a direct stimulatory effect, but may
      indirectly promote Y. pestis biofilm production by facilitating the alternate
      carbon source expression profile. Additionally, we assessed the impact of the
      carbon storage regulator protein, CsrA, upon Y. pestis biofilm production.
      Contrary to what has been described for E. coli, Y. pestis biofilm formation was
      found to be enhanced by CsrA. Regardless of media composition and available
      carbon source, deletion of csrA significantly impaired Y. pestis biofilm
      production. CsrA was found to promote Y. pestis biofilm production independent of
      glycogen regulation. Loss of csrA did not significantly alter relative hmsH,
      hmsP, or hmsT mRNA abundance. However, deletion of hmsP in the csrA-deficient
      mutant enabled excessive biofilm production, suggesting CsrA enables potent Y.
      pestis biofilm production through cyclic diguanylate regulation. 

PMID- 26305457
TI  - Body Condition Indices Predict Reproductive Success but Not Survival in a
      Sedentary, Tropical Bird.
AB  - Body condition may predict individual fitness because those in better condition
      have more resources to allocate towards improving their fitness. However, the
      hypothesis that condition indices are meaningful proxies for fitness has been
      questioned. Here, we ask if intraspecific variation in condition indices predicts
      annual reproductive success and survival. We monitored a population of Neochmia
      phaeton (crimson finch), a sedentary, tropical passerine, for reproductive
      success and survival over four breeding seasons, and sampled them for commonly
      used condition indices: mass adjusted for body size, muscle and fat scores,
      packed cell volume, hemoglobin concentration, total plasma protein, and
      heterophil to lymphocyte ratio. Our study population is well suited for this
      research because individuals forage in common areas and do not hold territories
      such that variation in condition between individuals is not confounded by
      differences in habitat quality. Furthermore, we controlled for factors that are
      known to impact condition indices in our study population (e.g., breeding stage)
      such that we assessed individual condition relative to others in the same
      context. Condition indices that reflect energy reserves predicted both the
      probability of an individual fledging young and the number of young produced that
      survived to independence, but only during some years. Those that were relatively
      heavy for their body size produced about three times more independent young
      compared to light individuals. That energy reserves are a meaningful predictor of
      reproductive success in a sedentary passerine supports the idea that energy
      reserves are at least sometimes predictors of fitness. However, hematological
      indices failed to predict reproductive success and none of the indices predicted
      survival. Therefore, some but not all condition indices may be informative, but
      because we found that most indices did not predict any component of fitness, we
      question the ubiquitous interpretation of condition indices as surrogates for
      individual quality and fitness. 

PMID- 26305458
TI  - Association between Maternal and Child Dietary Diversity: An Analysis of the
      Ghana Demographic and Health Survey.
AB  - OBJECTIVE (S): This study examined the association between maternal and child
      dietary diversity in a population-based national sample in Ghana. METHODS: The
      data for this analysis are from the 2008 Ghana Demographic and Health Survey. We
      used data obtained from 1187 dyads comprised of mothers' ages 15-49 and their
      youngest child (ages 6-36 months). Maternal and child dietary diversity scores
      (DDS) were created based on the mother's recall of her own and her child's
      consumption of 15 food groups, during the 24 hours prior to the in-home survey.
      The same food groups were used to compose both maternal and child DDS. Linear
      regression was used to assess the relationship between the predicted outcome-
      child DDS--and maternal DDS, taking into account child age and sex, maternal
      factors (age, education, occupation, literacy, empowerment, number of antenatal
      visits as an indicator of health care use), household Wealth Index, and
      urban/rural place of residence. RESULTS: There was a statistically significant
      positive association between child and maternal DDS, after adjusting for all
      other variables. A difference of one food group in mother's consumption was
      associated with a difference of 0.72 food groups in the child's food consumption
      (95% CI: 0.63, 0.82). Also, statistically significant positive associations were
      observed such that higher child DDS was associated with older child age, and with
      greater women's empowerment. CONCLUSIONS: The results show a significant positive
      association between child and maternal DD, after accounting for the influence of
      child, maternal and household level factors. Since the likely path of influence
      is that maternal DDS impacts child DDS, public health efforts to improve child
      health may be strengthened by promoting maternal DDS due to its potential for a
      widened effect on the entire family.

PMID- 26305459
TI  - Plasma exchange for chronic inflammatory demyelinating polyradiculoneuropathy.
AB  - BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is
      an uncommon progressive or relapsing paralysing disease caused by inflammation of
      the peripheral nerves. If the hypothesis that it is due to autoimmunity is
      correct, removal of autoantibodies in the blood by plasma exchange should be
      beneficial. OBJECTIVES: To assess the effects of plasma exchange for treating
      CIDP. SEARCH METHODS: On 30 June 2015, we searched the Cochrane Neuromuscular
      Disease Group Specialized Register, the Cochrane Central Register for Controlled
      Trials (CENTRAL), MEDLINE, EMBASE, CINAHL Plus, and LILACS. We also scrutinised
      the bibliographies of the trials, contacted the trial authors and other disease
      experts, and searched trials registries for ongoing studies. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) or quasi-RCTs in participants of any age
      comparing plasma exchange with sham treatment or no treatment. DATA COLLECTION
      AND ANALYSIS: Two review authors independently selected the trials, extracted the
      data, and assessed risk of bias. Where possible the review authors combined data
      according to the methods of the Cochrane Neuromuscular Disease Review Group. MAIN
      RESULTS:  PRIMARY OUTCOME MEASURE: one cross-over trial including 18 participants
      showed after four weeks, 2 (95% confidence interval (CI) 0.8 to 3.0) points more
      improvement on an 11-point disability scale with plasma exchange (10 exchanges
      over four weeks) than with sham exchange. Rapid deterioration after plasma
      exchange occurred in eight of 12 who had improved. SECONDARY OUTCOME MEASURES:
      when we combined the results of this cross-over trial and a trial with 29
      participants treated in a parallel-group design, there were 31 points (95% CI 16
      to 45) more improvement on an impairment scale (maximum score 280) after plasma
      exchange (six exchanges over three weeks) than after sham exchange. There were
      significant improvements in both trials in an electrophysiological measure, the
      proximally evoked compound muscle action potential, after three or four weeks.
      Nonrandomised evidence indicates that plasma exchange induces adverse events in
      3% to 17% of procedures. These events are sometimes serious. Both trials had a
      low risk of bias. A trial that showed no significant difference in the benefit
      between plasma exchange and intravenous immunoglobulin is included in the
      Cochrane review of intravenous immunoglobulin for this condition. AUTHORS'
      CONCLUSIONS: Moderate- to high-quality evidence from two small trials shows that
      plasma exchange provides significant short-term improvement in disability,
      clinical impairment, and motor nerve conduction velocity in CIDP but rapid
      deterioration may occur afterwards. Adverse events related to difficulty with
      venous access, use of citrate, and haemodynamic changes are not uncommon. We need
      more research to identify agents that will prolong the beneficial action of
      plasma exchange.

PMID- 26305460
TI  - Correction: Unveiling Undercover Cropland Inside Forests Using Landscape
      Variables: A Supplement to Remote Sensing Image Classification.

PMID- 26305461
TI  - Folded Elastic Strip-Based Triboelectric Nanogenerator for Harvesting Human
      Motion Energy for Multiple Applications.
AB  - A folded elastic strip-based triboelectric nanogenerator (FS-TENG) made from two
      folded double-layer elastic strips of Al/PET and PTFE/PET can achieve multiple
      functions by low frequency mechanical motion. A single FS-TENG with strip width
      of 3 cm and length of 27 cm can generate a maximum output current, open-circuit
      voltage, and peak power of 55 MUA, 840 V, and 7.33 mW at deformation frequency of
      4 Hz with amplitude of 2.5 cm, respectively. This FS-TENG can work as a weight
      sensor due to its good elasticity. An integrated generator assembled by four FS
      TENGs (IFS-TENG) can harvest the energy of human motion like flapping hands and
      walking steps. In addition, the IFS-TENG combined with electromagnetically
      induced electricity can achieve a completely self-driven doorbell with flashing
      lights. Moreover, a box-like generator integrated by four IFS-TENGs inside can
      work in horizontal or random motion modes and can be improved to harvest energy
      in all directions. This work promotes the research of completely self-driven
      systems and energy harvesting of human motion for applications in our daily life.

PMID- 26305462
TI  - Belief Propagation Algorithm for Portfolio Optimization Problems.
AB  - The typical behavior of optimal solutions to portfolio optimization problems with
      absolute deviation and expected shortfall models using replica analysis was
      pioneeringly estimated by S. Ciliberti et al. [Eur. Phys. B. 57, 175 (2007)];
      however, they have not yet developed an approximate derivation method for finding
      the optimal portfolio with respect to a given return set. In this study, an
      approximation algorithm based on belief propagation for the portfolio
      optimization problem is presented using the Bethe free energy formalism, and the
      consistency of the numerical experimental results of the proposed algorithm with
      those of replica analysis is confirmed. Furthermore, the conjecture of H. Konno
      and H. Yamazaki, that the optimal solutions with the absolute deviation model and
      with the mean-variance model have the same typical behavior, is verified using
      replica analysis and the belief propagation algorithm. 

PMID- 26305463
TI  - Genome-Wide Analysis of PAPS1-Dependent Polyadenylation Identifies Novel Roles
      for Functionally Specialized Poly(A) Polymerases in Arabidopsis thaliana.
AB  - The poly(A) tail at 3' ends of eukaryotic mRNAs promotes their nuclear export,
      stability and translational efficiency, and changes in its length can strongly
      impact gene expression. The Arabidopsis thaliana genome encodes three canonical
      nuclear poly(A) polymerases, PAPS1, PAPS2 and PAPS4. As shown by their different
      mutant phenotypes, these three isoforms are functionally specialized, with PAPS1
      modifying organ growth and suppressing a constitutive immune response. However,
      the molecular basis of this specialization is largely unknown. Here, we have
      estimated poly(A)-tail lengths on a transcriptome-wide scale in wild-type and
      paps1 mutants. This identified categories of genes as particularly strongly
      affected in paps1 mutants, including genes encoding ribosomal proteins, cell
      division factors and major carbohydrate-metabolic proteins. We experimentally
      verified two novel functions of PAPS1 in ribosome biogenesis and redox
      homoeostasis that were predicted based on the analysis of poly(A)-tail length
      changes in paps1 mutants. When overlaying the PAPS1-dependent effects observed
      here with coexpression analysis based on independent microarray data, the two
      clusters of transcripts that are most closely coexpressed with PAPS1 show the
      strongest change in poly(A)-tail length and transcript abundance in paps1 mutants
      in our analysis. This suggests that their coexpression reflects at least partly
      the preferential polyadenylation of these transcripts by PAPS1 versus the other
      two poly(A)-polymerase isoforms. Thus, transcriptome-wide analysis of poly(A)
      tail lengths identifies novel biological functions and likely target transcripts
      for polyadenylation by PAPS1. Data integration with large-scale co-expression
      data suggests that changes in the relative activities of the isoforms are used as
      an endogenous mechanism to co-ordinately modulate plant gene expression. 

PMID- 26305464
TI  - The Advanced Lipoxidation end Product Precursor Malondialdehyde Induces IL-17E
      Expression and Skews Lymphocytes to the th17 Subset.
AB  - Malondialdehyde (MDA) is a highly reactive endogenous product of thromboxane
      synthesis in the prostagland and lipid peroxidation by reactive oxygen species.
      Elevated MDA levels occur in diabetes and atherosclerotic plaques. The aim of
      this study was to examine the molecular mechanisms of MDA-induced IL-17E cytokine
      expression and its effect on T-cell differentiation. Real-time PCR, RT-PCR and
      ELISA were used to assess the expression of IL-17 family cytokines in Jurkat T
      cells and human peripheral blood lymphocytes (PBLCs) from diabetic subjects.
      Luciferase reporter assays were used for the promoter activation study.
      Pharmacological inhibitors were used for signaling pathway experiments. FACS
      analyses were used to measure the Th1, Th2 and Th17 subset levels. MDA induced
      significant (2- to 3-fold; p < 0.01) generation of IL-17E mRNA in a dose- and
      time-dependent manner in Jurkat T-cells and PBLCs. Elevated IL-17E mRNA levels
      were found in the lymphocytes from diabetic subjects. The increased IL-17E
      protein and mRNA levels correlate well with serum MDA levels from diabetic
      patients. Transient transfection of plasmid containing the minimum IL-17E
      promoter region (pIL-17E-Luc) showed a significant (2-fold; p < 0.01) increase in
      luciferase activity. Pretreatment of lymphocytes with pharmacological inhibitors
      showed the involvement of antioxidant, NF-kB, p38MAPK, PKC and ERK signaling
      pathways. Quantification of the Th1, Th2 and Th17 cell population in PBLCs via
      FACS analyses revealed an increase in the Th17 subset. These results show that
      MDA transcriptionally upregulates the expression of IL-17E in lymphocytes and
      alters lymphocyte differentiation towards the pathogenic Th17 subset. 

PMID- 26305466
TI  - The Epigenome of Schistosoma mansoni Provides Insight about How Cercariae Poise
      Transcription until Infection.
AB  - BACKGROUND: Chromatin structure can control gene expression and can define
      specific transcription states. For example, bivalent methylation of histone H3K4
      and H3K27 is linked to poised transcription in vertebrate embryonic stem cells
      (ESC). It allows them to rapidly engage specific developmental pathways. We
      reasoned that non-vertebrate metazoans that encounter a similar developmental
      constraint (i.e. to quickly start development into a new phenotype) might use a
      similar system. Schistosomes are parasitic platyhelminthes that are characterized
      by passage through two hosts: a mollusk as intermediate host and humans or
      rodents as definitive host. During its development, the parasite undergoes
      drastic changes, most notable immediately after infection of the definitive host,
      i.e. during the transition from the free-swimming cercariae into adult worms.
      METHODOLOGY/PRINCIPAL FINDINGS: We used Chromatin Immunoprecipitation followed by
      massive parallel sequencing (ChIP-Seq) to analyze genome-wide chromatin structure
      of S. mansoni on the level of histone modifications (H3K4me3, H3K27me3, H3K9me3,
      and H3K9ac) in cercariae, schistosomula and adults (available at
      http://genome.univ-perp.fr). We saw striking differences in chromatin structure
      between the developmental stages, but most importantly we found that cercariae
      possess a specific combination of marks at the transcription start sites (TSS)
      that has similarities to a structure found in ESC. We demonstrate that in
      cercariae no transcription occurs, and we provide evidences that cercariae do not
      possess large numbers of canonical stem cells. CONCLUSIONS/SIGNIFICANCE: We
      describe here a broad view on the epigenome of a metazoan parasite. Most notably,
      we find bivalent histone H3 methylation in cercariae. Methylation of H3K27 is
      removed during transformation into schistosomula (and stays absent in adults) and
      transcription is activated. In addition, shifts of H3K9 methylation and
      acetylation occur towards upstream and downstream of the transcriptional start
      site (TSS). We conclude that specific H3 modifications are a phylogenetically
      older and probably more general mechanism, i.e. not restricted to stem cells, to
      poise transcription. Since adult couples must form to cause the disease symptoms,
      changes in histone modifications appear to be crucial for pathogenesis and
      represent therefore a therapeutic target.

PMID- 26305465
TI  - Prevalence of CADASIL and Fabry Disease in a Cohort of MRI Defined Younger Onset
      Lacunar Stroke.
AB  - BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy (CADASIL), caused by mutations in the NOTCH3
      gene, is the most common monogenic disorder causing lacunar stroke and cerebral
      small vessel disease (SVD). Fabry disease (FD) due to mutations in the GLA gene
      has been suggested as an underdiagnosed cause of stroke, and one feature is SVD.
      Previous studies reported varying prevalence of CADASIL and FD in stroke, likely
      due to varying subtypes studied; no studies have looked at a large cohort of
      younger onset SVD. We determined the prevalence in a well-defined, MRI-verified
      cohort of apparently sporadic patients with lacunar infarct. METHODS: Caucasian
      patients with lacunar infarction, aged <=70 years (mean age 56.7 (SD8.6)), were
      recruited from 72 specialist stroke centres throughout the UK as part of the
      Young Lacunar Stroke DNA Resource. Patients with a previously confirmed monogenic
      cause of stroke were excluded. All MRI's and clinical histories were reviewed
      centrally. Screening was performed for NOTCH3 and GLA mutations. RESULTS: Of 994
      subjects five had pathogenic NOTCH3 mutations (R169C, R207C, R587C, C1222G and
      C323S) all resulting in loss or gain of a cysteine in the NOTCH3 protein. All
      five patients had confluent leukoaraiosis (Fazekas grade >=2). CADASIL prevalence
      overall was 0.5% (95% CI 0.2%-1.1%) and among cases with confluent leukoaraiosis
      1.5% (95% CI 0.6%-3.3%). No classic pathogenic FD mutations were found; one
      patient had a missense mutation (R118C), associated with late-onset FD.
      CONCLUSION: CADASIL cases are rare and only detected in SVD patients with
      confluent leukoaraiosis. No definite FD cases were detected.

PMID- 26305467
TI  - The Regulation of Muscle Structure and Metabolism by Mio/dChREBP in Drosophila.
AB  - All cells require energy to perform their specialized functions. Muscle is
      particularly sensitive to the availability of nutrients due to the high-energy
      requirement for muscle contraction. Therefore the ability of muscle cells to
      obtain, store and utilize energy is essential for the function of these cells.
      Mio, the Drosophila homolog of carbohydrate response element binding protein
      (ChREBP), has recently been identified as a nutrient responsive transcription
      factor important for triglyceride storage in the fly fat body. However, the
      function of Mio in muscle is unknown. In this study, we characterized the role of
      Mio in controlling muscle function and metabolism. Decreasing Mio levels using
      RNAi specifically in muscle results in increased thorax glycogen storage. Adult
      Mio-RNAi flies also have a flight defect due to altered myofibril shape and size
      in the indirect flight muscles as shown by electron microscopy. Myofibril size is
      also decreased in flies just before emerging from their pupal cases, suggesting a
      role for Mio in myofibril development. Together, these data indicate a novel role
      for Mio in controlling muscle structure and metabolism and may provide a
      molecular link between nutrient availability and muscle function. 

PMID- 26305469
TI  - Human Lymphatic Mesenteric Vessels: Morphology and Possible Function of Aminergic
      and NPY-ergic Nerve Fibers.
AB  - BACKGROUND: The lymphatic vessels have been studied in different organs from a
      morphological to a clinical point of view. Nevertheless, the knowledge of the
      catecholaminergic control of the lymphatic circulation is still incomplete. The
      aim of this work is to study the presence and distribution of the
      catecholaminergic and NPY-ergic nerve fibers in the whole wall of the human
      mesenteric lymphatic vessels in order to obtain knowledge about their morphology
      and functional significance. MATERIALS AND METHODS: The following experimental
      procedures were performed: 1) drawing of tissue containing lymphatic vessels; 2)
      cutting of tissue; 3) staining of tissue; 4) staining of nerve fibers; 5)
      histofluorescence microscopy for the staining of catecholaminergic nerve fibers;
      6) staining of neuropeptide Y like-immune reactivity; 7) biochemical assay of
      proteins; 8) measurement of noradrenaline; 9) quantitative analysis of images;
      10) statistical analysis of data. RESULTS: Numerous nerve fibers run in the wall
      of lymphatic vessels. Many of them are catecholaminergic in nature. Some nerve
      fibers are NPY-positive. The biochemical results on noradrenaline amounts are in
      agreement with morphological results on catecholaminergic nerve fibers. Moreover,
      the morphometric results, obtained by the quantitative analysis of images and the
      subsequent statistical analysis of data, confirm all our morphological and
      biochemical data. CONCLUSIONS: The knowledge of the physiological or pathological
      mechanism regulating the functions of the lymphatic system is incomplete.
      Nevertheless the catecholaminergic nerve fibers of the human mesenteric lymphatic
      vessels come from the adrenergic periarterial plexuses of the mesenterial
      arterial bed. NPY-ergic nerve fibers may modulate the microcirculatory
      mesenterial bed in different pathological conditions.

PMID- 26305468
TI  - A Catalog of Proteins Expressed in the AG Secreted Fluid during the Mature Phase
      of the Chinese Mitten Crabs (Eriocheir sinensis).
AB  - The accessory gland (AG) is an important component of the male reproductive
      system of arthropods, its secretions enhance fertility, some AG proteins bind to
      the spermatozoa and affect its function and properties. Here we report the first
      comprehensive catalog of the AG secreted fluid during the mature phase of the
      Chinese mitten crab (Eriocheir sinensis). AG proteins were separated by one
      dimensional gel electrophoresis and analyzed by reverse phase high-performance
      liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS).
      Altogether, the mass spectra of 1173 peptides were detected (1067 without decoy
      and contaminants) which allowed for the identification of 486 different proteins
      annotated upon the NCBI database (http://www.ncbi.nlm.nih.gov/) and our
      transcritptome dataset. The mass spectrometry proteomics data have been deposited
      at the ProteomeXchange with identifier PXD000700. An extensive description of the
      AG proteome will help provide the basis for a better understanding of a number of
      reproductive mechanisms, including potentially spermatophore breakdown, dynamic
      functional and morphological changes in sperm cells and sperm acrosin enzyme
      vitality. Thus, the comprehensive catalog of proteins presented here can serve as
      a valuable reference for future studies of sperm maturation and regulatory
      mechanisms involved in crustacean reproduction. 

PMID- 26305470
TI  - Nebivolol Ameliorates Hepatic Ischemia/Reperfusion Injury on Liver But Not on
      Distant Organs.
AB  - INTRODUCTION: Hepatic ischemia/reperfusion injury may occur after large tumor
      resection and liver transplantation procedures. Nitric oxide was shown to have
      protective effects on ischemia/reperfusion injury. Nebivolol is a compound that
      has been reported to improve nitric oxide release. We evaluated the effects of
      nebivolol in a rat liver ischemia/reperfusion model. METHODS: A total of 40 rats
      were randomly divided into four groups (n = 10 each). Group I underwent only
      laparotomy, Group II was administered nebivolol and then underwent laparotomy,
      Group III underwent laparotomy and hepatic ischemia/reperfusion, and Group IV was
      administered nebivolol and then underwent laparotomy and hepatic
      ischemia/reperfusion. Serum AST, ALT, urea, and creatinine levels, and TAS and
      TOS levels of liver, lung, and kidney tissues were determined. Histopathological
      determination was also performed. RESULTS: Nebivolol significantly reduced liver
      function tests in group IV, but it did not improve renal functions. Oxidative
      stress and abnormal histopathological findings were found to be reduced in liver
      tissue in group IV. Although the oxidative stress was increased after hepatic
      ischemia/reperfusion, nebivolol could not reduce the oxidative stress in kidney
      tissue. There were no significant differences between group III and group IV in
      terms of the histopathological changes in kidney tissue. There were no
      significant differences in lung tissue between the groups. CONCLUSIONS: The
      results of this study suggest that nebivolol has protective effects on liver but
      not on distant organs in a hepatic ischemia/reperfusion injury model. These
      experimental findings indicate that nebivolol may be useful in the treatment of
      hepatic ischemia/reperfusion injury.

PMID- 26305471
TI  - A Multiplex Assay for Detection of Staphylococcal and Streptococcal Exotoxins.
AB  - Staphylococcal and streptococcal exotoxins, also known as superantigens, mediate
      a range of diseases including toxic shock syndrome, and they exacerbate skin,
      pulmonary and systemic infections caused by these organisms. When present in food
      sources they can cause enteric effects commonly known as food poisoning. A rapid,
      sensitive assay for the toxins would enable testing of clinical samples and
      improve surveillance of food sources. Here we developed a bead-based, two-color
      flow cytometry assay using single protein domains of the beta chain of T cell
      receptors engineered for high-affinity for staphylococcal (SEA, SEB and TSST-1)
      and streptococcal (SpeA and SpeC) toxins. Site-directed biotinylated forms of
      these high-affinity agents were used together with commercial, polyclonal, anti
      toxin reagents to enable specific and sensitive detection with SD50 values of 400
      pg/ml (SEA), 3 pg/ml (SEB), 25 pg/ml (TSST-1), 6 ng/ml (SpeA), and 100 pg/ml
      (SpeC). These sensitivities were in the range of 4- to 80-fold higher than
      achieved with standard ELISAs using the same reagents. A multiplex format of the
      assay showed reduced sensitivity due to higher noise associated with the use of
      multiple polyclonal agents, but the sensitivities were still well within the
      range necessary for detection in food sources or for rapid detection of toxins in
      culture supernatants. For example, the assay specifically detected toxins in
      supernatants derived from cultures of Staphylococcus aureus. Thus, these reagents
      can be used for simultaneous detection of the toxins in food sources or culture
      supernatants of potential pathogenic strains of Staphylococcus aureus and
      Streptococcus pyogenes. 

PMID- 26305472
TI  - The map-based genome sequence of Spirodela polyrhiza aligned with its
      chromosomes, a reference for karyotype evolution.
AB  - Duckweeds are aquatic monocotyledonous plants of potential economic interest with
      fast vegetative propagation, comprising 37 species with variable genome sizes
      (0.158-1.88 Gbp). The genomic sequence of Spirodela polyrhiza, the smallest and
      the most ancient duckweed genome, needs to be aligned to its chromosomes as a
      reference and prerequisite to study the genome and karyotype evolution of other
      duckweed species. We selected physically mapped bacterial artificial chromosomes
      (BACs) containing Spirodela DNA inserts with little or no repetitive elements as
      probes for multicolor fluorescence in situ hybridization (mcFISH), using an
      optimized BAC pooling strategy, to validate its physical map and correlate it
      with its chromosome complement. By consecutive mcFISH analyses, we assigned the
      originally assembled 32 pseudomolecules (supercontigs) of the genomic sequences
      to the 20 chromosomes of S. polyrhiza. A Spirodela cytogenetic map containing 96
      BAC markers with an average distance of 0.89 Mbp was constructed. Using a
      cocktail of 41 BACs in three colors, all chromosome pairs could be individualized
      simultaneously. Seven ancestral blocks emerged from duplicated chromosome
      segments of 19 Spirodela chromosomes. The chromosomally integrated genome of S.
      polyrhiza and the established prerequisites for comparative chromosome painting
      enable future studies on the chromosome homoeology and karyotype evolution of
      duckweed species. 

PMID- 26305473
TI  - Prenatal Paracetamol Exposure and Wheezing in Childhood: Causation or
      Confounding?
AB  - BACKGROUND: Several studies have reported an increased risk of wheezing in the
      children of mothers who used paracetamol during pregnancy. We evaluated to what
      extent this association is explained by confounding. METHODS: We investigated the
      association between maternal paracetamol use in the first and third trimester of
      pregnancy and ever wheezing or recurrent wheezing/asthma in infants in the NINFEA
      cohort study. Risks ratios (RR) and 95% confidence intervals (CI) were estimated
      after adjustment for confounders, including maternal infections and antibiotic
      use during pregnancy. RESULTS: The prevalence of maternal paracetamol use was
      30.6% during the first and 36.7% during the third trimester of pregnancy. The
      prevalence of ever wheezing and recurrent wheezing/asthma was 16.9% and 5.6%,
      respectively. After full adjustment, the RR for ever wheezing decreased from 1.25
      [1.07-1.47] to 1.10 [0.94-1.30] in the first, and from 1.26 [1.08-1.47] to 1.10
      [0.93-1.29] in the third trimester. A similar pattern was observed for recurrent
      wheezing/asthma. Duration of maternal paracetamol use was not associated with
      either outcome. Further analyses on paracetamol use for three non-infectious
      disorders (sciatica, migraine, and headache) revealed no increased risk of
      wheezing in children. CONCLUSION: The association between maternal paracetamol
      use during pregnancy and infant wheezing is mainly, if not completely explained
      by confounding.

PMID- 26305474
TI  - Vascular Proteomics Reveal Novel Proteins Involved in SMC Phenotypic Change: OLR1
      as a SMC Receptor Regulating Proliferation and Inflammatory Response.
AB  - Neointimal hyperplasia of vascular smooth muscle cells (VSMC) plays a critical
      role in atherosclerotic plaque formation and in-stent restenosis, but the
      underlying mechanisms are still incompletely understood. We performed a
      proteomics study to identify novel signaling molecules organizing the VSMC
      hyperplasia. The differential proteomics analysis in a balloon-induced injury
      model of rat carotid artery revealed that the expressions of 44 proteins are
      changed within 3 days post injury. The combination of cellular function assays
      and a protein network analysis further demonstrated that 27 out of 44 proteins
      constitute key signaling networks orchestrating the phenotypic change of VSMC
      from contractile to epithelial-like synthetic. Among the list of proteins, the in
      vivo validation specifically revealed that six proteins (Rab15, ITR, OLR1,
      PDHbeta, PTPepsilon) are positive regulators for VSMC hyperplasia. In particular,
      the OLR1 played dual roles in the VSMC hyperplasia by directly mediating oxidized
      LDL-induced monocyte adhesion via NF-kappaB activation and by assisting the PDGF
      induced proliferation/migration. Importantly, OLR1 and PDGFRbeta were associated
      in close proximity in the plasma membrane. Thus, this study elicits the protein
      network organizing the phenotypic change of VSMC in the vascular injury diseases
      such as atherosclerosis and discovers OLR1 as a novel molecular link between the
      proliferative and inflammatory responses of VSMCs. 

PMID- 26305475
TI  - Dysfunction of the frontolimbic region during swear word processing in young
      adolescents with Internet gaming disorder.
AB  - Although the Internet is an important tool in our daily life, the control of
      Internet use is necessary to address difficult problems. This study set out with
      the aim of assessing the cognitive control of affective events in Internet gaming
      disorder (IGD) and has examined the influence of IGD on neural activities with
      regard to swear words in young adolescents. We demonstrated the differences
      between adolescents with IGD and healthy control adolescents (HC) with respect to
      swear, negative and neutral word conditions. Swear words induced more activation
      in regions related to social interaction and emotional processing such as the
      superior temporal sulcus, right temporoparietal junction and orbitofrontal cortex
      (OFC) when compared with negative words. In this study, adolescents with IGD
      exhibited reduced activation in the right OFC related to cognitive control and in
      the dorsal anterior cingulate cortex (dACC) related to social rejection during
      the swear word condition. In addition, adolescents with IGD were negatively
      correlated with activity in the right amygdala toward swear words, indicating the
      important role of the amygdala in the control of aggression in adolescents with
      IGD. These findings enhance our understanding of social-emotional perception in
      adolescents with IGD. 

PMID- 26305476
TI  - Neural networks underlying implicit and explicit moral evaluations in
      psychopathy.
AB  - Psychopathy, characterized by symptoms of emotional detachment, reduced guilt and
      empathy and a callous disregard for the rights and welfare of others, is a strong
      risk factor for immoral behavior. Psychopathy is also marked by abnormal
      attention with downstream consequences on emotional processing. To examine the
      influence of task demands on moral evaluation in psychopathy, functional magnetic
      resonance imaging was used to measure neural response and functional connectivity
      in 88 incarcerated male subjects (28 with Psychopathy Checklist Revised (PCL-R)
      scores ? 30) while they viewed dynamic visual stimuli depicting interpersonal
      harm and interpersonal assistance in two contexts, implicit and explicit. During
      the implicit task, high psychopathy was associated with reduced activity in the
      dorsolateral prefrontal cortex and caudate when viewing harmful compared with
      helpful social interactions. Functional connectivity seeded in the right amygdala
      and right temporoparietal junction revealed decreased coupling with the anterior
      cingulate cortex (ACC), anterior insula, striatum and ventromedial prefrontal
      cortex. In the explicit task, higher trait psychopathy predicted reduced signal
      change in ACC and amygdala, accompanied by decreased functional connectivity to
      temporal pole, insula and striatum, but increased connectivity with dorsal ACC.
      Psychopathy did not influence behavioral performance in either task, despite
      differences in neural activity and functional connectivity. These findings
      provide the first direct evidence that hemodynamic activity and neural coupling
      within the salience network are disrupted in psychopathy, and that the effects of
      psychopathy on moral evaluation are influenced by attentional demands.

PMID- 26305477
TI  - Apoptotic markers in cultured fibroblasts correlate with brain metabolites and
      regional brain volume in antipsychotic-naive first-episode schizophrenia and
      healthy controls.
AB  - Cultured fibroblasts from first-episode schizophrenia patients (FES) have shown
      increased susceptibility to apoptosis, which may be related to glutamate
      dysfunction and progressive neuroanatomical changes. Here we determine whether
      apoptotic markers obtained from cultured fibroblasts in FES and controls
      correlate with changes in brain glutamate and N-acetylaspartate (NAA) and
      regional brain volumes. Eleven antipsychotic-naive FES and seven age- and gender
      matched controls underwent 3-Tesla magnetic resonance imaging scanning. Glutamate
      plus glutamine (Glx) and NAA levels were measured in the anterior cingulate (AC)
      and the left thalamus (LT). Hallmarks of apoptotic susceptibility (caspase-3
      baseline activity, phosphatidylserine externalization and chromatin condensation)
      were measured in fibroblast cultures obtained from skin biopsies after inducing
      apoptosis with staurosporine (STS) at doses of 0.25 and 0.5 MUM. Apoptotic
      biomarkers were correlated to brain metabolites and regional brain volume. FES
      and controls showed a negative correlation in the AC between Glx levels and
      percentages of cells with condensed chromatin (CC) after both apoptosis
      inductions (STS 0.5 MUM: r = -0.90; P = 0.001; STS 0.25 MUM: r = -0.73; P =
      0.003), and between NAA and cells with CC (STS 0.5 MUM induction r = -0.76; P =
      0.002; STS 0.25 MUM r = -0.62; P = 0.01). In addition, we found a negative
      correlation between percentages of cells with CC and regional brain volume in the
      right supratemporal cortex and post-central region (STS 0.25 and 0.5 MUM; P <
      0.05 family-wise error corrected (FWEc)). We reveal for the first time that
      peripheral markers of apoptotic susceptibility may correlate with brain
      metabolites, Glx and NAA, and regional brain volume in FES and controls, which is
      consistent with the neuroprogressive theories around the onset of the
      schizophrenia illness.

PMID- 26305478
TI  - Epigenetic and genetic variation at SKA2 predict suicidal behavior and post
      traumatic stress disorder.
AB  - Traumatic stress results in hypothalamic pituitary adrenal (HPA) axis
      abnormalities and an increased risk to both suicidal behaviors and post-traumatic
      stress disorder (PTSD). Previous work out of our laboratory identified SKA2 DNA
      methylation associations with suicidal behavior in the blood and brain of
      multiple cohorts. Interaction of SKA2 with stress predicted suicidal behavior
      with ~80% accuracy. SKA2 is hypothesized to reduce the ability to suppress
      cortisol following stress, which is of potentially high relevance in traumatized
      populations. Our objective was to investigate the interaction of SKA2 and trauma
      exposure on HPA axis function, suicide attempt and PTSD. SKA2 DNA methylation at
      Illumina HM450 probe cg13989295 was assessed for association with suicidal
      behavior and PTSD metrics in the context of Child Trauma Questionnaire (CTQ)
      scores in 421 blood and 61 saliva samples from the Grady Trauma Project (GTP)
      cohort. Dexamethasone suppression test (DST) data were evaluated for a subset of
      209 GTP subjects. SKA2 methylation interacted with CTQ scores to predict lifetime
      suicide attempt in saliva and blood with areas under the receiver operator
      characteristic curve (AUCs) of 0.76 and 0.73 (95% confidence interval (CI): 0.6
      0.92, P = 0.003, and CI: 0.65-0.78, P < 0.0001) and to mediate the suppression of
      cortisol following DST (beta = 0.5 +/- 0.19, F = 1.51, degrees of freedom (df) =
      12/167, P = 0.0096). Cumulatively, the data suggest that epigenetic variation at
      SKA2 mediates vulnerability to suicidal behaviors and PTSD through dysregulation
      of the HPA axis in response to stress.

PMID- 26305479
TI  - Cultivating Professional Allies for Sexual Minority Youth: A Community-Based
      Educational Intervention.
AB  - Sexual minority youth (SMY) face multiple risks in their daily lives that may
      influence their need for supportive care. Health and social service providers
      have unique opportunities to provide culturally competent services to these
      youth. This article describes a community-based educational intervention created
      to increase providers' knowledge, skills, and intention to support SMY. Based on
      the Information-Motivation-Behavioral Skills model, this pilot study found that
      for a diverse sample of multidisciplinary professionals (n = 2,850), the odds of
      behavioral intention (BI) to support SMY were significantly higher when trainings
      were relevant to the professionals' experience (OR = 1.3), were sensitive (OR =
      1.3), developed skills (OR = 1.1), and incorporated policy (OR = 1.2).
      Implications for the delivery of community-based trainings are provided. 

PMID- 26305482
TI  - Deletion of a C-terminal intrinsically disordered region of WRINKLED1 affects its
      stability and enhances oil accumulation in Arabidopsis.
AB  - WRINKLED1 (WRI1) is a key transcription factor governing plant oil biosynthesis.
      We characterized three intrinsically disordered regions (IDRs) in Arabidopsis
      WRI1, and found that one C-terminal IDR of AtWRI1 (IDR3) affects the stability of
      AtWRI1. Analysis by bimolecular fluorescence complementation and yeast-two-hybrid
      assays indicated that the IDR3 domain does not determine WRI1 stability by
      interacting with BTB/POZ-MATH proteins connecting AtWRI1 with CULLIN3-based E3
      ligases. Analysis of the WRI1 sequence revealed that a putative PEST motif
      (proteolytic signal) is located at the C-terminal region of AtWRI1(IDR) (3). We
      also show that a 91 amino acid domain at the C-terminus of AtWRI1 without the
      PEST motif is sufficient for transactivation. We found that removal of the PEST
      motif or mutations in putative phosphorylation sites increased the stability of
      AtWRI1, and led to increased oil biosynthesis when these constructs were
      transiently expressed in tobacco leaves. Oil content was also increased in the
      seeds of stable transgenic wri1-1 plants expressing AtWRI1 with mutations in the
      IDR3-PEST motif. Taken together, our data suggest that intrinsic disorder of
      AtWRI1(IDR3) may facilitate exposure of the PEST motif to protein kinases. Thus,
      phosphorylation of the PEST motif in the AtWRI1(IDR) (3) domain may affect AtWRI1
      mediated plant oil biosynthesis. The results obtained here suggest a means to
      increase accumulation of oils in plant tissues through WRI1 engineering. 

PMID- 26305481
TI  - Decreased 11beta-Hydroxysteroid Dehydrogenase 1 Level and Activity in Murine
      Pancreatic Islets Caused by Insulin-Like Growth Factor I Overexpression.
AB  - We have reported a high expression of IGF-I in pancreatic islet beta-cells of
      transgenic mice under the metallothionein promoter. cDNA microarray analysis of
      the islets revealed that the expression of 82 genes was significantly altered
      compared to wild-type mice. Of these, 11beta-hydroxysteroid dehydrogenase 1
      (11beta-HSD1), which is responsible for the conversion of inert cortisone (11
      dehydrocorticosterone, DHC in rodents) to active cortisol (corticosterone) in the
      liver and adipose tissues, has not been identified previously as an IGF-I target
      in pancreatic islets. We characterized the changes in its protein level, enzyme
      activity and glucose-stimulated insulin secretion. In freshly isolated islets,
      the level of 11beta-HSD1 protein was significantly lower in MT-IGF mice. Using
      dual-labeled immunofluorescence, 11beta-HSD1 was observed exclusively in glucagon
      producing, islet alpha-cells but at a lower level in transgenic vs. wild-type
      animals. MT-IGF islets also exhibited reduced enzymatic activities. Dexamethasone
      (DEX) and DHC inhibited glucose-stimulated insulin secretion from freshly
      isolated islets of wild-type mice. In the islets of MT-IGF mice, 48-h pre
      incubation of DEX caused a significant decrease in insulin release, while the
      effect of DHC was largely blunted consistent with diminished 11beta-HSD1
      activity. In order to establish the function of intracrine glucocorticoids, we
      overexpressed 11beta-HSD1 cDNA in MIN6 insulinoma cells, which together with DHC
      caused apoptosis and a significant decrease in proliferation. Both effects were
      abolished with the treatment of an 11beta-HSD1 inhibitor. Our results demonstrate
      an inhibitory effect of IGF-I on 11beta-HSD1 expression and activity within the
      pancreatic islets, which may mediate part of the IGF-I effects on cell
      proliferation, survival and insulin secretion. 

PMID- 26305483
TI  - Global Warming: Predicting OPEC Carbon Dioxide Emissions from Petroleum
      Consumption Using Neural Network and Hybrid Cuckoo Search Algorithm.
AB  - BACKGROUND: Global warming is attracting attention from policy makers due to its
      impacts such as floods, extreme weather, increases in temperature by 0.7 degrees
      C, heat waves, storms, etc. These disasters result in loss of human life and
      billions of dollars in property. Global warming is believed to be caused by the
      emissions of greenhouse gases due to human activities including the emissions of
      carbon dioxide (CO2) from petroleum consumption. Limitations of the previous
      methods of predicting CO2 emissions and lack of work on the prediction of the
      Organization of the Petroleum Exporting Countries (OPEC) CO2 emissions from
      petroleum consumption have motivated this research. METHODS/FINDINGS: The OPEC
      CO2 emissions data were collected from the Energy Information Administration.
      Artificial Neural Network (ANN) adaptability and performance motivated its choice
      for this study. To improve effectiveness of the ANN, the cuckoo search algorithm
      was hybridised with accelerated particle swarm optimisation for training the ANN
      to build a model for the prediction of OPEC CO2 emissions. The proposed model
      predicts OPEC CO2 emissions for 3, 6, 9, 12 and 16 years with an improved
      accuracy and speed over the state-of-the-art methods. CONCLUSION: An accurate
      prediction of OPEC CO2 emissions can serve as a reference point for propagating
      the reorganisation of economic development in OPEC member countries with the view
      of reducing CO2 emissions to Kyoto benchmarks--hence, reducing global warming.
      The policy implications are discussed in the paper.

PMID- 26305484
TI  - Association of plasma fatty acid composition with plasma irisin levels in normal
      weight and overweight/obese children.
AB  - BACKGROUND: Irisin has been suggested to protect against overweight. There are no
      previous data on the association of plasma fatty acid (FA) composition with
      plasma irisin. OBJECTIVES: We studied the association of FA composition with
      plasma irisin in normal weight and overweight/obese children. METHODS: This cross
      sectional study included pre-pubertal children (388 normal weight children and 55
      overweight/obese children); 6-9 years of age, taking part in the Physical
      Activity and Nutrition in Children Study. After an overnight fast, we measured
      plasma FA composition by gas chromatography and plasma irisin levels by enzyme
      linked immunosorbent assay. RESULTS: Higher proportion of total monounsaturated
      fatty acids in plasma cholesteryl esters (CEs) (beta = 0.139, P = 0.003) and
      phospholipids (PLs) (beta = 0.147, P = 0.002) and lower proportion of total
      polyunsaturated fatty acids in plasma CE (beta = -0.130, P = 0.006) and PL (beta
      = -0.165, P < 0.001) were associated with higher plasma irisin level in the whole
      study group. The association of plasma FA composition with plasma irisin level
      was stronger among overweight/obese children compared to normal weight children.
      Higher proportion of gamma-linolenic acid (beta = 0.324, P = 0.017) and lower
      proportion of linoleic acid (beta = -0.397, P = 0.005) in plasma CE were related
      to higher plasma irisin level among overweight/obese children, indicating the
      direct association of estimated D6D activity in plasma CE (beta = 0.343, P =
      0.011) with plasma irisin. Furthermore, higher proportion of oleic acid in plasma
      CE (beta = 0.345, P = 0.012) and PL (beta = 0.292, P = 0.033) and higher
      proportion of adrenic acid (beta = 0.366, P = 0.008) and docosapentaenoic acid
      (beta = 0.351, P = 0.010) in plasma PL were associated with higher plasma irisin
      level among overweight/obese children. CONCLUSION: Metabolically unfavourable
      plasma FA profile was associated with higher plasma irisin level especially in
      overweight/obese children, suggesting that excess body fat might modulate these
      relationships.

PMID- 26305485
TI  - Spontaneous laterality in mouse Crl:CD1.
AB  - Lateralization developed very early in evolution and it is a characteristic of a
      wide range of representatives from the animal kingdom. The aim of the present
      study was to examine the spontaneous laterality in mice (Mus musculus) with the T
      maze test. We wanted to check if this kind of functional asymmetry occurs at a
      population level, and also if there are gender differences in this regard. The
      study involved 40 mice Crl:CD1. The research procedure was simple: mice had to
      choose one arm of the T-shaped apparatus to find the exit. The animals performed
      the 10 trails one after another. We took into account only the animals' fist
      reactions while preparing results. Most of the animals (68%) chose the right arm
      of the maze. The lateralization was stronger among females--75% of them had
      preferences for the right side. The majority of animals, which preferred the
      right side, were from the food deprivation group. However, the results did not
      unequivocally resolve whether mice evince the functional asymmetry at the
      population level, or whether there are gender differences in this area. Further
      research with a larger group and multiple observations for each animal are
      required to answer these questions.

PMID- 26305486
TI  - The first complete mitochondrial genome of the Microtus ochrogaster.
AB  - Microtus ochrogaster, a small vole, found in central North America. Recently the
      genome sequencing had been done, but no more information of its mitochondrial
      reported. Herein, we first assembled the complete mitochondrial genome sequence
      of Microtus ochrogaster. It is a 16 292 bp long sequence with most mitogenome's
      characteristic structure, 13 protein-coding genes, two of rRNA genes, 22 of tRNA
      genes, one D-loop region, one repeat region, and three STS regions. The GC
      content of our fresh sequence is 40%. It can verify the accuracy and utility of
      new determined mitogenome sequences by the phylogenetic analysis, based on the
      whole mitogenome alignment with Microtus fortis calamorum, Microtus levis, and
      Microtus rossiaemeridionalis, which is closest relative to Microtus ochrogaster.
      We expect that using the full mitogenome to address taxonomic issues and study
      the related evolution events.

PMID- 26305487
TI  - A Simple Evaporation Method for Large-Scale Production of Liquid Crystalline
      Lipid Nanoparticles with Various Internal Structures.
AB  - We present a simple and industrially accessible method of producing liquid
      crystalline lipid nanoparticles with various internal structures based on
      phytantriol, Pluronic F127, and vitamin E acetate. Bilayer vesicles were produced
      when an ethanolic solution dissolving the lipid components was mixed with
      deionized water. After the evaporation of ethanol from the aqueous mixture,
      vesicles were transformed into lipid-filled liquid crystalline nanoparticles with
      well-defined internal structures such as hexagonal lattices (mostly inverted
      cubic Pn3m), lined or coiled pattern (inverted hexagonal H2), and disordered
      structure (inverse microemulsion, L2), depending on the compositions. Further
      studies suggested that their internal structures were also affected by
      temperature. The internal structures were characterized from cryo-TEM and small
      angle X-ray scattering results. Microcalorimetry studies were performed to
      investigate the degree of molecular ordering/crystallinity of lipid components
      within the nanostructures. From the comparative studies, we demonstrated the
      present method could produce the lipid nanoparticles with similar characteristics
      to those made from a conventional method. More importantly, the production only
      requires simple tools for mixing and ethanol evaporation and it is possible to
      produce 10 kg or so per batch of aqueous lipid nanoparticles dispersions,
      enabling the large-scale production of the liquid crystalline nanoparticles for
      various biomedical applications. 

PMID- 26305488
TI  - Spontaneous Transition of Self-assembled Hydrogel Fibrils into Crystalline
      Microtubes Enables a Rational Strategy To Stabilize the Hydrogel State.
AB  - Hydrogel fibril and crystal formation are related self-assembly processes that
      provide materials with distinct emergent properties. The relationship between
      fibril and crystal growth is poorly understood, and efforts to engineer
      controlled hydrogelation vs crystallization via small molecule self-assembly
      currently depend on empirical approaches. Herein, we report the dynamic
      transition of self-assembled hydrogel fibrils of a phenylalanine (Phe)
      derivative, Fmoc-p-nitrophenylalanine (Fmoc-4-NO2-Phe), to crystalline
      microtubes. As has been shown with other Fmoc-Phe derivatives, Fmoc-4-NO2-Phe
      spontaneously self-assembles into amyloid-like fibrils that form an entangled
      hydrogel network when suspended in water. However, Fmoc-4-NO2-Phe fibrils
      uniquely transform over time into crystalline microtubes. Hydrogel fibrils appear
      to be a kinetic state with microtube crystals more thermodynamically favored.
      This dynamic transition from fibril to crystal has enabled a high-resolution
      structural analysis of the packing orientation of these self-assembled materials.
      Taking cues from this structural analysis, we demonstrate a rational strategy for
      stabilization of the kinetic Fmoc-4-NO2-Phe hydrogel fibrils. These results
      represent significant advances in our understanding of the dynamic nature of self
      assembly processes and in our ability to rationally engineer these processes to
      provide materials with desired emergent properties. 

PMID- 26305489
TI  - Adaptation of a Gaussia princeps Luciferase reporter system in Candida albicans
      for in vivo detection in the Galleria mellonella infection model.
AB  - For the past 10 years, mini-host models and in particular the greater wax moth
      Galleria mellonella have tended to become a surrogate for murine models of fungal
      infection mainly due to cost, ethical constraints and ease of use. Thus, methods
      to better assess the fungal pathogenesis in G. mellonella need to be developed.
      In this study, we implemented the detection of Candida albicans cells expressing
      the Gaussia princeps luciferase in its cell wall in infected larvae of G.
      mellonella. We demonstrated that detection and quantification of luminescence in
      the pulp of infected larvae is a reliable method to perform drug efficacy and C.
      albicans virulence assays as compared to fungal burden assay. Since the linearity
      of the bioluminescent signal, as compared to the CFU counts, has a correlation of
      R(2) = 0.62 and that this method is twice faster and less labor intensive than
      classical fungal burden assays, it could be applied to large scale studies. We
      next visualized and followed C. albicans infection in living G. mellonella larvae
      using a non-toxic and water-soluble coelenterazine formulation and a CCD camera
      that is commonly used for chemoluminescence signal detection. This work allowed
      us to follow for the first time C. albicans course of infection in G. mellonella
      during 4 days.

PMID- 26305490
TI  - Rho GTPase RAC1 at the Molecular Interface Between Genetic and Environmental
      Factors of Autism Spectrum Disorders.

PMID- 26305491
TI  - Modular architecture of protein binding units for designing properties of
      cellulose nanomaterials.
AB  - Molecular biomimetic models suggest that proteins in the soft matrix of
      nanocomposites have a multimodular architecture. Engineered proteins were used
      together with nanofibrillated cellulose (NFC) to show how this type of
      architecture leads to function. The proteins consist of two cellulose-binding
      modules (CBM) separated by 12-, 24-, or 48-mer linkers. Engineering the linkers
      has a considerable effects on the interaction between protein and NFC in both wet
      colloidal state and a dry film. The protein optionally incorporates a
      multimerizing hydrophobin (HFB) domain connected by another linker. The modular
      structure explains effects in the hydrated gel state, as well as the deformation
      of composite materials through stress distribution and crosslinking. Based on
      this work, strategies can be suggested for tuning the mechanical properties of
      materials through the coupling of protein modules and their interlinking
      architectures. 

PMID- 26305492
TI  - Large-Area Synthesis of High-Quality Uniform Few-Layer MoTe2.
AB  - The controlled synthesis of large-area, atomically thin molybdenum ditelluride
      (MoTe2) crystals is crucial for its various applications based on the attractive
      properties of this emerging material. In this work, we developed a chemical vapor
      deposition synthesis to produce large-area, uniform, and highly crystalline few
      layer 2H and 1T' MoTe2 films. It was found that these two different phases of
      MoTe2 can be grown depending on the choice of Mo precursor. Because of the highly
      crystalline structure, the as-grown few-layer 2H MoTe2 films display electronic
      properties that are comparable to those of mechanically exfoliated MoTe2 flakes.
      Our growth method paves the way for the large-scale application of MoTe2 in high
      performance nanoelectronics and optoelectronics. 

PMID- 26305493
TI  - The olive leaf extract oleuropein exerts protective effects against oxidant
      induced cell death, concurrently displaying pro-oxidant activity in human
      hepatocarcinoma cells.
AB  - OBJECTIVES: Oleuropein (OP), the predominant natural constituent of leaves of the
      olive tree, exerts anti-inflammatory and antioxidant effects. The purpose of this
      study was to assess the protective effects of OP under the conditions of paraquat
      (PQ)-induced oxidative stress in vitro, using the human hepatocarcinoma cell
      line, HepG2. METHODS: Cell viability and death were determined using the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and 4',6-diamidino-2
      phenylindole-propidium iodide staining, respectively. Superoxide anion and lipid
      peroxidation levels were evaluated using nitroblue tetrazolium and thiobarbituric
      acid-reactive substances assays, respectively. Apoptosis was assessed by
      measuring poly(ADP-ribose) polymerase (PARP) and caspase-3 (Casp-3) cleavage via
      immunoblotting and immunofluorescence analyses. RESULTS: PQ induced a decrease in
      cellular viability by promoting necrosis through a mechanism involving superoxide
      generation and nuclear translocation of cleaved Casp-3. Co-treatment with OP
      afforded significant protection against the suppressive effects of PQ, as evident
      from increased cell viability, reduction of Casp-3 immunofluorescence, and
      normalization of beta-tubulin expression levels. Unexpectedly, these OP-mediated
      protective effects were associated with increased superoxide and malondialdehyde
      generation and PARP cleavage. DISCUSSION: OP protects HepG2 cells against PQ
      induced necrosis by suppressing Casp-3 cleavage while concomitantly acting as a
      pro-oxidant agent. This paradoxical mechanism of action of OP requires further
      investigation.

PMID- 26305494
TI  - Carbon Multiplicity Editing in Long-Range Heteronuclear Correlation NMR
      Experiments: A Valuable Tool for the Structure Elucidation of Natural Products.
AB  - A recently developed NMR method to simultaneously obtain both long-range
      heteronuclear correlations and carbon multiplicity information in a single
      experiment, ME-selHSQMBC, is demonstrated as a potentially useful technique for
      chemical shift assignment and structure elucidation of natural products
      presenting complicated NMR spectra. Carbon multiplicities, even for C/CH2 and odd
      for CH/CH3 resonances, can be distinguished directly from the relative
      positive/negative phase of cross-peaks. In addition, connectivity networks can be
      further extended by incorporating a TOCSY propagation step. Staurosporine (1) and
      sungucine (2) are utilized as model compounds to demonstrate these techniques. 

PMID- 26305495
TI  - Pre-Morbid Developmental Vulnerabilities in Children With Newly Diagnosed Acute
      Lymphoblastic Leukemia (ALL).
AB  - BACKGROUND: Not all children with acute lymphoblastic leukemia (ALL) were
      developing in a typical manner prior to diagnosis. Pre-existing developmental
      vulnerabilities (DV) may be related to long-term neuropsychological sequelae
      following ALL treatment, yet little is known about the prevalence or nature of
      prior DV in this population. PROCEDURE: Children with newly diagnosed ALL aged 2
      18 years (n = 115) were screened for DV by asking parents about the child's prior
      developmental history and with the Developmental Profile-3 (DP-3). RESULTS:
      Twenty-six participants (23% of total sample) screened positive for prior DV,
      with one or more of the following: delayed early motor and/or language milestones
      that required intervention (n = 17), prior diagnosis of Down syndrome (n = 3),
      prior diagnosis of autism spectrum disorder (n = 1), prior diagnosis of attention
      deficit/hyperactivity disorder and/or learning disability (n = 6), or prior
      neurological conditions (n = 5). CONCLUSIONS: A sizable proportion of children
      with newly diagnosed ALL have pre-morbid DV that could potentially make them more
      vulnerable to reduced educational opportunities during treatment and neurotoxic
      late effects following treatment. Identification of the subset of children with
      ALL and DV is essential to direct early interventions and to study their long
      term outcomes.

PMID- 26305496
TI  - Infective endocarditis: does a new 16S rDNA set of primers improve the
      microbiological diagnosis?
AB  - BACKGROUND: In infective endocarditis (IE), blood cultures are negative in 2.5
      31% of cases because of a previously prescribed antimicrobial treatment.
      Molecular methods may represent an alternative to conventional microbiological
      techniques to identify the causative agent. The aim of this prospective study was
      to evaluate the performance of a new primer pair (341F/785R) for 16S rDNA
      amplification in heart valves compared with primers 91E/13BS already used for the
      diagnosis of IE. The primer pair 341F/785R was previously selected in silico to
      allow 16S rDNA amplification for a large coverage of bacterial species. RESULTS:
      A total of 74 patients suspected of having IE were included in this study. IE was
      diagnosed in 55 of these patients using the modified Duke criteria, which was the
      gold standard here. 91E/13BS primers were more sensitive than 341F/785R primers:
      38/55 (69.1%) samples were positive using 91E/13BS primers against 28/55 (50.9%)
      with 341F/785R (p = 0.013). When at least one of the two molecular methods was
      positive, the sensitivity and specificity of 16S rDNA amplification was 72.7% and
      94.7%, respectively. CONCLUSION: Even if the new primer pair 341F/785R seemed
      promising in silico, it was less sensitive for 16S rDNA amplification in heart
      valves than the 91E/13BS pair already used. This study underlines a lack of
      standardization for 16S rDNA amplification for clinical samples.

PMID- 26305497
TI  - Many ways to break a heart.
AB  - A mutant transcription factor that has been linked to congenital heart disease
      has wider effects than previously thought. 

PMID- 26305498
TI  - Structural dynamics of E. coli single-stranded DNA binding protein reveal DNA
      wrapping and unwrapping pathways.
AB  - Escherichia coli single-stranded (ss)DNA binding (SSB) protein mediates genome
      maintenance processes by regulating access to ssDNA. This homotetrameric protein
      wraps ssDNA in multiple distinct binding modes that may be used selectively in
      different DNA processes, and whose detailed wrapping topologies remain
      speculative. Here, we used single-molecule force and fluorescence spectroscopy to
      investigate E. coli SSB binding to ssDNA. Stretching a single ssDNA-SSB complex
      reveals discrete states that correlate with known binding modes, the likely ssDNA
      conformations and diffusion dynamics in each, and the kinetic pathways by which
      the protein wraps ssDNA and is dissociated. The data allow us to construct an
      energy landscape for the ssDNA-SSB complex, revealing that unwrapping energy
      costs increase the more ssDNA is unraveled. Our findings provide insights into
      the mechanism by which proteins gain access to ssDNA bound by SSB, as
      demonstrated by experiments in which SSB is displaced by the E. coli recombinase
      RecA. 

PMID- 26305499
TI  - Regulation of mRNA translation during mitosis.
AB  - Passage through mitosis is driven by precisely-timed changes in transcriptional
      regulation and protein degradation. However, the importance of translational
      regulation during mitosis remains poorly understood. Here, using ribosome
      profiling, we find both a global translational repression and identified ~200
      mRNAs that undergo specific translational regulation at mitotic entry. In
      contrast, few changes in mRNA abundance are observed, indicating that regulation
      of translation is the primary mechanism of modulating protein expression during
      mitosis. Interestingly, 91% of the mRNAs that undergo gene-specific regulation in
      mitosis are translationally repressed, rather than activated. One of the most
      pronounced translationally-repressed genes is Emi1, an inhibitor of the anaphase
      promoting complex (APC) which is degraded during mitosis. We show that full APC
      activation requires translational repression of Emi1 in addition to its
      degradation. These results identify gene-specific translational repression as a
      means of controlling the mitotic proteome, which may complement post
      translational mechanisms for inactivating protein function.

PMID- 26305501
TI  - Self-awareness in the retina.
AB  - Proteins called gamma-protocadherins are essential for the establishment of
      working circuits of neurons in the retina. 

PMID- 26305500
TI  - A mitochondria-anchored isoform of the actin-nucleating spire protein regulates
      mitochondrial division.
AB  - Mitochondrial division, essential for survival in mammals, is enhanced by an
      inter-organellar process involving ER tubules encircling and constricting
      mitochondria. The force for constriction is thought to involve actin
      polymerization by the ER-anchored isoform of the formin protein inverted formin 2
      (INF2). Unknown is the mechanism triggering INF2-mediated actin polymerization at
      ER-mitochondria intersections. We show that a novel isoform of the formin
      binding, actin-nucleating protein Spire, Spire1C, localizes to mitochondria and
      directly links mitochondria to the actin cytoskeleton and the ER. Spire1C binds
      INF2 and promotes actin assembly on mitochondrial surfaces. Disrupting either
      Spire1C actin- or formin-binding activities reduces mitochondrial constriction
      and division. We propose Spire1C cooperates with INF2 to regulate actin assembly
      at ER-mitochondrial contacts. Simulations support this model's feasibility and
      demonstrate polymerizing actin filaments can induce mitochondrial constriction.
      Thus, Spire1C is optimally positioned to serve as a molecular hub that links
      mitochondria to actin and the ER for regulation of mitochondrial division. 

PMID- 26305502
TI  - Mitotic arrest induced in human DU145 prostate cancer cells in response to KHC-4
      treatment.
AB  - In this study, the antitumor activity of KHC-4 was analyzed using human prostate
      cancer (CaP) cells and the underlining anticancer mechanisms of KHC-4 were
      identified. KHC-4 inhibited cell proliferation and induced cytotoxicity in the
      castration-resistant CaP DU145 cell line. The most effective concentration of KHC
      4 was 0.1 MUM. Cell cycle analysis demonstrated that KHC-4 treatment caused G2/M
      arrest and a subsequent increase in the sub-G1 population. Furthermore, KHC-4 is
      up-regulated p21, p27, and p53 in a time- and concentration-dependent manner. The
      exposure of cells to KHC-4 induced Cdk1/cyclin B1 complex activity, which led to
      cell cycle arrest. Moreover, KHC-4 inhibited the activities of MMP-2 and MMP-9 to
      inhibit tumor cell metastasis. (c) 2015 Wiley Periodicals, Inc. Environ Toxicol
      31: 1879-1887, 2016.

PMID- 26305503
TI  - Meanings of "acceptance" for patients with long-term pain when starting
      rehabilitation.
AB  - PURPOSE: The study aimed to elucidate the meaning of acceptance in relation to
      the lived body and sense of self when entering a pain rehabilitation programme.
      METHODS: Six women and three men with long-term pain were interviewed. The
      interviews were analysed according to interpretative phenomenological analysis.
      RESULTS: The analysis revealed three different meaning structures, first:
      acceptance as a process of personal empowerment, "the only way forward". Here,
      the individuals expressed that the body felt integrated: a trusting cooperation
      between self and body gave rise to hope. Second: acceptance as an equivocal
      project, a possible but challenging way forward. The hopeful insight was there,
      acknowledging that acceptance was the way to move forward, but there was also
      uncertainty and doubt about one's ability with a body ambiguous and confusing,
      difficult but important to understand. Third, in acceptance as a threat and a
      personal failure, "no way forward" the integration of the aching body in sense of
      self was impossible and pain was incomprehensible, unacceptable and unfair. Pain
      was the cause of feeling stuck in the body, affecting the sense of self and the
      person's entire life. CONCLUSIONS: The meaning of acceptance was related to
      acceptance of the persistency of pain, to how the individual related to the lived
      body and the need for changes in core aspects of self, and to the issue of
      whether to include others in the struggle of learning to move on with a
      meaningful life. IMPLICATIONS FOR REHABILITATION: Healthcare professionals should
      be aware that individuals with long-term pain conceptualize and hold different
      meanings of acceptance when starting rehabilitation; this should be considered
      and addressed in rehabilitation programmes. The meaning given to acceptance is
      related to the experience of the lived body and the sense of self, as well as to
      getting legitimization/acceptance by others; therefore these aspects need to be
      considered during rehabilitation. The process of achieving acceptance seems to
      embrace different processes which can be understood as, and facilitated by, an
      embodied learning process. The bodily existential challenges presented in the
      present study, for example to develop an integrated and cooperative relationship
      with the painful body, can inspire health professionals to develop interventions
      and communication strategies focusing on the lived body. A wide range of
      competencies in rehabilitation clinics seems to be needed.

PMID- 26305504
TI  - Biotic-Abiotic Interactions: Factors that Influence Peptide-Graphene
      Interactions.
AB  - Understanding the factors that influence the interaction between biomolecules and
      abiotic surfaces is of utmost interest in biosensing and biomedical research.
      Through phage display technology, several peptides have been identified as
      specific binders to abiotic material surfaces, such as gold, graphene, silver,
      and so forth. Using graphene-peptide as our model abiotic-biotic pair, we
      investigate the effect of graphene quality, number of layers, and the underlying
      support substrate effect on graphene-peptide interactions using both experiments
      and computation. Our results indicate that graphene quality plays a significant
      role in graphene-peptide interactions. The graphene-biomolecule interaction
      appears to show no significant dependency on the number of graphene layers or the
      underlying support substrate. 

PMID- 26305505
TI  - Determination of a large set of beta-adrenergic agonists in animal matrices based
      on ion mobility and mass separations.
AB  - While the coupling of traveling wave ion mobility spectrometry (TWIMS) and mass
      spectrometry is mainly reported for structural purposes, we studied its potential
      in enhancing compounds analysis such as growth promoters used in livestock
      animals at trace concentrations. beta-Adrenergic agonists have been selected as
      model compounds since they exhibit a range of close physicochemical properties
      leading to analytical issues using classical approaches. In this paper, the
      potential of Synapt G2-S (Q-TWIM-TOF MS) has been investigated for sensitive and
      specific detection of a range of these synthetic phenethanolamines in various
      complex biological matrices (retina, meat, and urine) from bovine considered as
      relevant in the context of detecting beta-adrenergic agonists use in animals. In
      particular, the specificity of the additional information provided by the TWIMS
      (i.e., collision cross section) together with the interest of the extra dimension
      of separation is discussed. 

PMID- 26305506
TI  - Molecular Dynamic Indicators of the Photoswitching Properties of Green
      Fluorescent Proteins.
AB  - Reversibly photoswitchable fluorescent proteins (RSFPs) are highly useful probes
      for a range of applications including diffraction-unlimited fluorescence
      microscopy. It was previously shown that reversible photoswitching not only
      involves cis-trans isomerization and protonation-deprotonation of the chromophore
      but also results in a marked difference in beta-barrel flexibility. In this work,
      we performed flexibility profiling and functional mode analysis (FMA) using
      molecular dynamics calculations to study how the flexibility of the RSFP beta
      barrel influences the photoswitching properties of several fluorescent proteins.
      We also used Partial Least-Squared (PLS) FMA to detect promising mutation sites
      for the modulation of photoswitching properties of RSFPs. Our results show that
      the flexibility of RSFP does depend on its state with a systematically higher
      flexibility in the dark state compared to the bright state. In particular our
      method highlights the importance of Val157 in Dronpa, which upon mutation yields
      a striking difference in the collective motions of the two mutants. Overall, we
      show that PLS-FMA yields information, complementary to static structures, that
      can guide the rational design of fluorescent proteins. 

PMID- 26305507
TI  - Unexpected DNA binding properties with correlated downstream biological
      applications in mono vs. bis-1,8-naphthalimide Ru(II)-polypyridyl conjugates.
AB  - The synthesis, spectroscopic characterisation and biological evaluation of mono-
      and bis-1,8-naphthalimide-conjugated ruthenium(ii)-polypyridyl complexes is
      presented. Spectroscopic DNA titrations, together with denaturation studies, show
      strong binding of both species to DNA through the naphthalimide arms. Linear and
      circular dichroism (LD and CD) spectroscopy reveal close association of the
      Ru(bpy)3(2+) core with DNA in the case of the mono-naphthalamide complex,
      [Ru(bpy)2(bpy-NAP)](2+). Significantly, binding by the second naphthalimide arm
      in the [Ru(bpy)2(bpy-NAP2)](2+) complex is found to displace the Ru(bpy)3(2+)
      centre from the DNA backbone. This 'negative allosteric effect' is found to have
      a dramatic influence on the photoinduced damage of plasmid DNA, and the viability
      of HeLa cancer cells upon photoactivation. Overall the study clearly maps and
      correlates the relationship between molecular structure, in vitro binding and
      activity, and in cellulo function. 

PMID- 26305509
TI  - Rebuttal to the Con Statement.

PMID- 26305508
TI  - Over-expression of ROR2 and Wnt5a cooperatively correlates with unfavorable
      prognosis in patients with non-small cell lung cancer.
AB  - We investigated the expression of receptor tyrosine kinase-like orphan receptor
      (ROR) 2 and Wnt5a and their prognostic significance in non-small cell lung cancer
      (NSCLC). Tissue microarray-based immunohistochemical analysis was performed to
      determine the expression of ROR2 and Wnt5a in 219 patients. mRNA expression of
      ROR2 and Wnt5a was examined in 20 pairs of NSCLC and matched adjacent normal
      tissues by real-time PCR. Compared with non-tumorous tissues, both mRNA
      expression and protein product of ROR2 and Wnt5a genes were significantly
      increased in NSCLC. c2 analysis revealed that high ROR2 or Wnt5a expression in
      NSCLC was significantly associated with advanced TNM stage. High expression of
      both ROR2 and Wnt5a was also related to advanced TNM stage. Multivariate analyses
      suggested that ROR2, Wnt5a and TNM stage were independent prognostic factors in
      NSCLC. Our clinical findings suggest that high ROR2 or Wnt5a expression is
      associated with poor prognosis in NSCLC, and combined detection of ROR2 and Wnt5a
      is helpful in predicting the prognosis of NSCLC. 

PMID- 26305510
TI  - Overview of challenges and opportunities in drug delivery and pharmaceutics.

PMID- 26305512
TI  - A New Index for the MMPI-2 Test for Detecting Dissimulation in Forensic
      Evaluations: A Pilot Study.
AB  - This pilot study is the starting point of a potentially broad research project
      aimed at identifying new strategies for assessing malingering during forensic
      evaluations. The forensic group was comprised of 67 males who were seeking some
      sort of certification (e.g., adoption, child custody, driver's license, issuance
      of gun permits, etc.); the nonforensic group was comprised of 62 healthy male
      volunteers. Each participant was administered the MMPI-2. Statistical analyses
      were conducted on obtained scores of 48 MMPI-2 scales. In the first step,
      parametric statistics were adopted to identify the best combination of MMPI-2
      scales that differentiated the two groups of participants. In the second step,
      frequency-based, nonparametric methods were used for diagnostic purposes.
      RESULTS: A model that utilized the best three predictors ("7-Pt", "L," and "1
      Hs") was developed and used to calculate the Forensic Evaluation Dissimulation
      Index (FEDI), which features satisfactory diagnostic accuracy (0.9), sensitivity
      (0.82), specificity (0.81), and likelihood ratio indices (LR+ = 4.32; LR- =
      0.22).

PMID- 26305514
TI  - Mining heart disease risk factors in clinical text with named entity recognition
      and distributional semantic models.
AB  - We present the design, and analyze the performance of a multi-stage natural
      language processing system employing named entity recognition, Bayesian
      statistics, and rule logic to identify and characterize heart disease risk factor
      events in diabetic patients over time. The system was originally developed for
      the 2014 i2b2 Challenges in Natural Language in Clinical Data. The system's
      strengths included a high level of accuracy for identifying named entities
      associated with heart disease risk factor events. The system's primary weakness
      was due to inaccuracies when characterizing the attributes of some events. For
      example, determining the relative time of an event with respect to the record
      date, whether an event is attributable to the patient's history or the patient's
      family history, and differentiating between current and prior smoking status. We
      believe these inaccuracies were due in large part to the lack of an effective
      approach for integrating context into our event detection model. To address these
      inaccuracies, we explore the addition of a distributional semantic model for
      characterizing contextual evidence of heart disease risk factor events. Using
      this semantic model, we raise our initial 2014 i2b2 Challenges in Natural
      Language of Clinical data F1 score of 0.838 to 0.890 and increased precision by
      10.3% without use of any lexicons that might bias our results. 

PMID- 26305513
TI  - An alternative database approach for management of SNOMED CT and improved patient
      data queries.
AB  - OBJECTIVE: SNOMED CT is the international lingua franca of terminologies for
      human health. Based in Description Logics (DL), the terminology enables data
      queries that incorporate inferences between data elements, as well as, those
      relationships that are explicitly stated. However, the ontologic and
      polyhierarchical nature of the SNOMED CT concept model make it difficult to
      implement in its entirety within electronic health record systems that largely
      employ object oriented or relational database architectures. The result is a
      reduction of data richness, limitations of query capability and increased systems
      overhead. The hypothesis of this research was that a graph database (graph DB)
      architecture using SNOMED CT as the basis for the data model and subsequently
      modeling patient data upon the semantic core of SNOMED CT could exploit the full
      value of the terminology to enrich and support advanced data querying capability
      of patient data sets. METHODS: The hypothesis was tested by instantiating a graph
      DB with the fully classified SNOMED CT concept model. The graph DB instance was
      tested for integrity by calculating the transitive closure table for the SNOMED
      CT hierarchy and comparing the results with transitive closure tables created
      using current, validated methods. The graph DB was then populated with 461,171
      anonymized patient record fragments and over 2.1 million associated SNOMED CT
      clinical findings. Queries, including concept negation and disjunction, were then
      run against the graph database and an enterprise Oracle relational database
      (RDBMS) of the same patient data sets. The graph DB was then populated with
      laboratory data encoded using LOINC, as well as, medication data encoded with
      RxNorm and complex queries performed using LOINC, RxNorm and SNOMED CT to
      identify uniquely described patient populations. RESULTS: A graph database
      instance was successfully created for two international releases of SNOMED CT and
      two US SNOMED CT editions. Transitive closure tables and descriptive statistics
      generated using the graph database were identical to those using validated
      methods. Patient queries produced identical patient count results to the Oracle
      RDBMS with comparable times. Database queries involving defining attributes of
      SNOMED CT concepts were possible with the graph DB. The same queries could not be
      directly performed with the Oracle RDBMS representation of the patient data and
      required the creation and use of external terminology services. Further, queries
      of undefined depth were successful in identifying unknown relationships between
      patient cohorts. CONCLUSION: The results of this study supported the hypothesis
      that a patient database built upon and around the semantic model of SNOMED CT was
      possible. The model supported queries that leveraged all aspects of the SNOMED CT
      logical model to produce clinically relevant query results. Logical disjunction
      and negation queries were possible using the data model, as well as, queries that
      extended beyond the structural IS_A hierarchy of SNOMED CT to include queries
      that employed defining attribute-values of SNOMED CT concepts as search
      parameters. As medical terminologies, such as SNOMED CT, continue to expand, they
      will become more complex and model consistency will be more difficult to assure.
      Simultaneously, consumers of data will increasingly demand improvements to query
      functionality to accommodate additional granularity of clinical concepts without
      sacrificing speed. This new line of research provides an alternative approach to
      instantiating and querying patient data represented using advanced computable
      clinical terminologies.

PMID- 26305515
TI  - Why Postoperative Pain Remains a Problem.
AB  - Despite great progress in our understanding and management of pain,
      undertreatment of postoperative pain is still a major problem. There are
      individual patient differences in terms of nociception and perception, as well as
      varying responses to pain management. Postoperative pain can impact on the length
      of hospital stay, mobilization after surgery, and patient satisfaction. --This
      report is adapted from paineurope 2015: Issue 1, (c)Haymarket Medical
      Publications Ltd, and is presented with permission. paineurope is provided as a
      service to pain management by Mundipharma International, LTD and is distributed
      free of charge to healthcare professionals in Europe. Archival issues can be
      viewed via the website: www.paineurope.com at which health professionals can find
      links to the original articles and request copies of the quarterly publication
      and access additional pain education and pain management resources.

PMID- 26305518
TI  - Clinical Flow Cytometric Screening of SAP and XIAP Expression Accurately
      Identifies Patients with SH2D1A and XIAP/BIRC4 Mutations.
AB  - INTRODUCTION: X-linked lymphoproliferative disease is caused by mutations in 2
      genes, SH2D1A and XIAP/BIRC4. Flow cytometric methods have been developed to
      detect the gene products, SAP and XIAP. However, there is no literature
      describing the accuracy of flow cytometric screening performed in a clinical lab
      setting. METHODS: We reviewed the clinical flow cytometric testing results for
      656 SAP and 586 XIAP samples tested during a three year period. Genetic testing
      was clinically performed as directed by the managing physician in 137 SAP (21%)
      and 115 XIAP (20%) samples. We included these samples for analyses of flow
      cytometric test accuracy. RESULTS: SH2D1A mutations were detected in 15/137
      samples. SAP expression was low in 13/15 (sensitivity 87%, CI 61-97%). Of the 122
      samples with normal sequencing, SAP was normal in 109 (specificity 89%, CI 82
      94%). The positive and negative predictive values were 50% and 98%, respectively.
      XIAP/BIRC4 mutations were detected in 19/115 samples. XIAP expression was low in
      18/19 (sensitivity 95%, CI 73-100%). Of the 96 samples with normal sequencing, 59
      had normal XIAP expression (specificity 61%, CI 51-71%). The positive and
      negative predictive values were 33% and 98%, respectively. Receiver operating
      characteristic analysis was able to improve the specificity to 75%. CONCLUSION:
      Clinical flow cytometric screening tests for SAP and XIAP deficiencies offer good
      sensitivity and specificity for detecting genetic mutations, and are
      characterized by high negative predictive values. We recommend these tests for
      patients suspected of having XLP1 or XLP2. (c) 2014 Clinical Cytometry Society.

PMID- 26305516
TI  - Utilizing the Trispyrazolyl Borate Ligand for the Mimicking of O2-Activating
      Mononuclear Nonheme Iron Enzymes.
AB  - Mononuclear, O2-activating nonheme iron enzymes are a fascinating class of
      metalloproteines, capable of realizing the most different reactions, ranging from
      C-H activation, via O atom transfer to C-C bond cleavage, in the course of O2
      activation. They can lead us the way to achieve similar reactions with comparable
      efficiency and selectivity in chemical laboratories, which would be highly
      desirable aiming at accessing value-added products or to achieve degradation of
      unwanted compounds. Hence, these enyzmes motivate attempts to construct
      artificial low-molecular weight analogues, mimicking structural or functional
      characteristics. Such models can, for instance, provide insights about which of
      the features inherent to an active site are essential and guarantee the enzyme
      function, and from this kind of information the minimal requirements for a
      biomimetic or bioinspired complex that may be applied in catalysis can be
      derived. On the other hand, they can contribute to an understanding of the enzyme
      functioning. In order to create such replicates, it is important to faithfully
      mimic the surroundings of the iron centers in their active sites. Most of them
      feature two histidine residues and one carboxylate donor, while a few exhibit a
      deceptively simple (His)3Fe active site. For the simulation of these, the
      trispyrazolyl borate ligand (Tp) particularly offers itself, as the facial
      arrangement of three pyrazole donors is reminiscent of the three histidine
      derived imidazole donors. The focus of this Account will be on
      bioinorganic/biomimetic research from our laboratory utilizing Tp ligands to
      develop molecular models for (i) two representatives of the (His)3Fe-enzyme
      family, namely, the cysteine dioxygenase (CDO) and acetyl acetone dioxygenase
      (Dke1), (ii) a related but less well-explored variant of the CDO-the 2
      aminoethanethiol dioxygenase-as well as (iii) the 2-His-1-carboxylate
      representative 1-aminocyclopropane-1-carboxylic acid oxidase (ACCO). The CDO
      catalyzes the dioxygenation of cysteine with O2 to give cysteine sulfinic acid,
      which could be mimicked at TpFe units in a realistic manner. Furthermore, the
      successful dioxygenation of 2-aminoethanethiol at the same complex metal
      fragments lends further support to the hypothesis that the active sites of CDO
      and the one of 2-aminoethanethiol dioxygenase, whose structure is unknown, are
      quite similar. Dke1 is capable of cleaving diketones and ketoesters to give the
      corresponding carboxylic acids and alpha-keto aldehydes, and Tp-based models have
      achieved comparable C-C bond cleavage reactions. The ACCO develops ethylene from
      ACC in the course of oxidation, and recently this has been achieved the first
      time for a TpFe model, too. 

PMID- 26305517
TI  - Drinking Motives, Alcohol Use, and Sexual Attraction in Youth.
AB  - Sexual minority youth were found to be more likely to drink alcohol during
      weekdays compared to heterosexual youth. Drinking during weekdays was associated
      with consuming alcohol as a coping strategy. Sexual minority youth also more
      frequently consumed alcohol to eliminate personal worries (coping) and to not be
      excluded by their peers (conformity). Sexual orientation-related alcohol problems
      should be addressed at an early stage. Such efforts are likely to be effective if
      insecurities and stress related to sexual orientation are addressed as well. 

PMID- 26305519
TI  - Hierarchical carbon framework wrapped Na3V2(PO4)3 as a superior high-rate and
      extended lifespan cathode for sodium-ion batteries.
AB  - Hierarchical carbon framework wrapped Na3 V2 (PO4 )3 (HCF-NVP) is successfully
      synthesized through chemical vapor deposition on pure Na3 V2 (PO4 )3 particles.
      Electrochemical experiments show that the HCF-NVP electrode can deliver a large
      reversible capacity (115 mA h g(-1) at 0.2 C), superior high-rate rate capability
      (38 mA h g(-1) at 500 C), and ultra-long cycling stability (54% capacity
      retention after 20 000 cycles). 

PMID- 26305520
TI  - Future Research Directions in Asthma. An NHLBI Working Group Report.
AB  - Asthma is a common chronic disease without cure. Our understanding of asthma
      onset, pathobiology, classification, and management has evolved substantially
      over the past decade; however, significant asthma-related morbidity and excess
      healthcare use and costs persist. To address this important clinical condition,
      the NHLBI convened a group of extramural investigators for an Asthma Research
      Strategic Planning workshop on September 18-19, 2014, to accelerate discoveries
      and their translation to patients. The workshop focused on (1) in utero and early
      life origins of asthma, (2) the use of phenotypes and endotypes to classify
      disease, (3) defining disease modification, (4) disease management, and (5)
      implementation research. This report summarizes the workshop and produces
      recommendations to guide future research in asthma. 

PMID- 26305521
TI  - Concierge and Second-Opinion Radiology: Review of Current Practices.
AB  - Radiology's core assets include the production, interpretation, and distribution
      of quality imaging studies. Second-opinion services and concierge practices in
      radiology aim to augment traditional services by providing patient-centered and
      physician-centered care, respectively. Patient centeredness enhances patients'
      understanding and comfort with their radiology tests and procedures and allows
      them to make better decisions about their health care. As the fee-for-service
      paradigm shifts to value-based care models, radiology practices have begun to
      diversify imaging service delivery and communication to coincide with the
      American College of Radiology Imaging 3.0 campaign. Physician-centered
      consultation allows for communication of evidence-based guidelines to assist
      referring physicians and other providers in making the most appropriate imaging
      or treatment decision for a specific clinical condition. There are disparate
      practice models and payment schema for the various second-opinion and concierge
      practices. This review article explores the current state and payment models of
      second-opinion and concierge practices in radiology. This review also includes a
      discussion on the benefits, roadblocks, and ethical issues that surround these
      novel types of practices. 

PMID- 26305522
TI  - Abuse-deterrent opioid formulations.

PMID- 26305523
TI  - A new subcutaneous immune globulin (HyQvia) for primary immunodeficiency.

PMID- 26305524
TI  - ReShape and Orbera--two gastric balloon devices for weight loss.

PMID- 26305525
TI  - Onexton gel for acne.

PMID- 26305527
TI  - Corneal Deformation Response in Patients With Primary Open-Angle Glaucoma and in
      Healthy Subjects Analyzed by Corvis ST.
AB  - PURPOSE: To compare corneal deformation response between patients with primary
      open-angle glaucoma (POAG) and healthy subjects. A prevalent case-control study
      was conducted, followed by an integrated meta-analysis. METHODS: Primary open
      angle glaucoma was confirmed by presence of glaucomatous optic disc damage with
      corresponding visual field defect after excluding secondary causes. Age-matched
      controls were recruited. Corvis ST (CST) was used to measure 10 parameters of
      corneal deformation response and central corneal thickness (CCT). The association
      between parameters of deformation response and clinical factors was assessed by
      the linear regression analyses. Differences in deformation response between POAG
      and healthy subjects were compared after adjusting for other factors. Eligible
      studies were identified by a systematic search of the PubMed, ISI Web of Science,
      and Embase databases; Web sites of professional associations; and the Google
      Scholar engine. RESULTS: This study included 37 patients with POAG and 36 healthy
      controls. Significant associations were found between IOP and the first
      applanation time (A1T), first applanation velocity (A1V), second applanation time
      (A2T), and second applanation velocity (A2V) in each group. The deformation
      amplitude (DA), A1V, and A2T were lower in the POAG group, whereas the A1T, A2V
      and peak distance (PD) were greater in the POAG group than in the healthy
      controls (all P < 0.05). Ten separate studies plus the present study, involving
      691 patients with POAG and 740 controls, were ultimately meta-analyzed. The
      significant differences in the DA, A1T, and A2T were further confirmed, with
      pooled weighted mean difference (WMD) of 0.13 mm (95% CI 0.04-0.23; P = 0.008)
      for A1T, -0.13 mm (95% CI -0.21 to -0.05; P = 0.001) for DA, and -0.46 ms (95% CI
      -0.70 to -0.22; P < 0.001) for A2T. CONCLUSIONS: The corneal response parameters
      provided by CST are informative for the assessment of corneal biomechanics.
      Patients with POAG showed significantly greater A1T and lower DA and A2T values
      than healthy controls, indicating a less deformable cornea in POAG patients.

PMID- 26305526
TI  - Evaluation of the Structure-Function Relationship in Glaucoma Using a Novel
      Method for Estimating the Number of Retinal Ganglion Cells in the Human Retina.
AB  - PURPOSE: We developed a simple method for estimating the number of retinal
      ganglion cells (RGCs) in the human retina using optical coherence tomography
      (OCT), compared it to a previous approach, and demonstrated its potential for
      furthering our understanding of the structure-function relationship in glaucoma.
      METHODS: Swept-source (ss) OCT data and 10-2 visual fields (VFs) were obtained
      from 43 eyes of 36 healthy controls, and 50 eyes of 50 glaucoma patients and
      suspects. Using estimates of RGC density from the literature and relatively few
      assumptions, estimates of the number of RGCs in the macula were obtained based on
      ssOCT-derived RGC layer thickness measurements. RESULTS: The RGC estimates were
      in general agreement with previously published values derived from histology,
      whereas a prior method based on VF sensitivity did not agree as well with
      histological data and had significantly higher (P = 0.001) and more variable (P <
      0.001) RGC estimates than the new method based on ssOCT. However, the RGC
      estimates of the new approach were not zero for extreme VF losses, suggesting
      that a residual, non-RGC contribution needs to be added. Finally, the new ssOCT
      derived RGC estimates were significantly (P < 0.001 to P = 0.018) related to VF
      sensitivity (Spearman's rho = 0.26-0.47), and, in contrast to claims made in
      prior studies, statistically significant RGC loss did not occur more often than
      statistically significant visual loss. CONCLUSIONS: The novel method for
      estimating RGCs yields values that are closer to histological estimates than
      prior methods, while relying on considerably fewer assumptions. Although the
      value added for clinical applications is yet to be determined, this approach is
      useful for assessing the structure-function relationship in glaucoma.

PMID- 26305528
TI  - Molecular Inflammation in the Contralateral Eye After Cataract Surgery in the
      First Eye.
AB  - PURPOSE: The purpose of this study was to assess the inflammatory status of the
      aqueous humor in the fellow eye after uneventful cataract surgery in the first
      eye. METHODS: At the screening stage, aqueous humor samples from 15 first-eye and
      15 second-eye cataract patients were collected just before cataract surgery and
      assayed using human cytokine antibody array. Screened cytokines were then
      verified using a suspension array system with aqueous humor samples obtained from
      35 first-eye and 36 second-eye cataract patients. RESULTS: The cytokine antibody
      array revealed that interleukin-1 receptor antagonist (Il-1ra) and macrophage
      inflammatory protein (MIP)-1a and MIP-1b were expressed at high levels in first
      eye patients and were lower in second-eye patients, whereas opposite trends were
      found for monocyte chemoattractant protein 1 (MCP-1) and for regulated on
      activation, normal T expressed and secreted (RANTES) (all, P < 0.05, Student's t
      test). However, only MCP-1 and IL-1ra were significantly different between the
      two groups after Bonferroni correction (both P < 0.00125). In the replication
      stage, the suspension cytokine array revealed that only MCP-1 expression was
      significantly greater in the aqueous humor of second-eye patients than in that of
      first-eye patients (P = 0.0067, Student's t-test). CONCLUSIONS: This study
      revealed that expression of MCP-1, a pain-related inflammatory chemokine, was
      significantly increased in aqueous humor in the contralateral eye after first-eye
      cataract surgery. This suggests there may be a sympathetic ophthalmic type
      uveitis in the contralateral eye after first-eye cataract surgery and that may
      help to explain why second-eye phacoemulsification is often more painful.
      (ClinicalTrials.gov number, NCT01824927.)

PMID- 26305529
TI  - Intraocular Pharmacokinetics of Aflibercept and Vascular Endothelial Growth
      Factor-A.
AB  - PURPOSE: To determine intraocular pharmacokinetics of aflibercept and VEGF-A in
      patients with neovascular age-related macular degeneration (nAMD) during a
      treatment period of 6 months. METHODS: Seven nonvitrectomized patients diagnosed
      with macular edema secondary to nAMD undergoing intravitreal injections (IVI) of
      aflibercept. Patients were treatment naive at least for the last 2 months and
      received intravitreal injection of 2 mg aflibercept for the first time. Aqueous
      humor samples were obtained prior to each injection procedure during a 6-month
      period: three times monthly, then bimonthly. Over all 35 samples were analyzed
      with ELISA for unbound VEGF-A and a self-developed assay for unbound aflibercept.
      RESULTS: In all cases, wet AMD was inactive after IVI. Unbound aflibercept could
      be detected in all samples. Initial mean concentration of aflibercept was 305.4
      +/- 43.8 MUg/mL and remained stable after the first injection with 0.8 +/- 0.5
      MUg/mL. Initial mean level of unbound VEGF-A was 190.7 +/- 26.9 pg/mL. A
      significant decrease of the concentration to 92.6 +/- 10.2 pg/mL (P < 0.05,
      Wilcoxon rank sum test) after the first injection was observed. This level
      remained stable during further treatment. CONCLUSIONS: Levels of unbound
      aflibercept and unbound VEGF-A remained stable after every month and every second
      month of IVI. The findings of these small case series support suggestions that
      treatment intervals with bimonthly IVI of aflibercept are sufficient due to a
      detectable remaining biologic active concentration of aflibercept.

PMID- 26305531
TI  - Associations Between the T280M and V249I SNPs in CX3CR1 and the Risk of Age
      Related Macular Degeneration.
AB  - PURPOSE: Two common single nucleotide polymorphisms (SNPs) in the CX3CR1 gene,
      T280M and V249I, have been reported to affect the risk of age-related macular
      degeneration (AMD) in several studies. The aim of the present study was to
      combine all published data on the relationship between these two variants and AMD
      susceptibility in a meta-analysis to clarify this association. METHODS: MEDLINE,
      EMBASE, and ISI Web of Science were searched for all eligible studies on the
      relationship between AMD and T280M and V249I variants. The pooled odds ratio (OR)
      with 95% confidence intervals (CIs) for each SNP in the allele frequency,
      homozygote, second codominant genotype, and dominant genotype models were
      calculated to evaluate the strength of this association. RESULTS: A total of 3017
      AMD cases and 4096 controls from eight studies were involved in this meta
      analysis. Both T280M and V249I SNPs exhibited significant associations with
      increased risk of AMD in the allele (T versus C: OR = 1.43, 95% CI: 1.06-1.91; A
      versus G: OR = 1.25, 95% CI: 1.01-1.55) and homozygous models (TT versus CC: OR =
      2.11, 95% CI: 1.00-4.43; AA versus GG: OR = 1.27, 95% CI: 1.00-1.61), while no
      significance association was observed for the codominant genotype model.
      Moreover, studies showing high linkage disequilibrium between these two variants
      demonstrated a significantly stronger connection between these SNPs and AMD risk,
      compared with the moderate linkage disequilibrium group. CONCLUSIONS: Significant
      evidence for a relationship between T280M and V249I variants in CX3CR1 in the
      homozygote state with increased susceptibility to AMD was reported. Further
      studies are needed to confirm these findings.

PMID- 26305530
TI  - Inhibition of DNA Methylation and Methyl-CpG-Binding Protein 2 Suppresses RPE
      Transdifferentiation: Relevance to Proliferative Vitreoretinopathy.
AB  - PURPOSE: The purpose of this study was to evaluate expression of methyl-CpG
      binding protein 2 (MeCP2) in epiretinal membranes from patients with
      proliferative vitreoretinopathy (PVR) and to investigate effects of inhibition of
      MeCP2 and DNA methylation on transforming growth factor (TGF)-beta-induced
      retinal pigment epithelial (RPE) cell transdifferentiation. METHODS: Expression
      of MeCP2 and its colocalization with cytokeratin and alpha-smooth muscle actin
      (alpha-SMA) in surgically excised PVR membranes was studied using
      immunohistochemistry. The effects of 5-AZA-2'-deoxycytidine (5-AZA-dC) on human
      RPE cell migration and viability were evaluated using a modified Boyden chamber
      assay and the colorimetric 3-(4,5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium
      bromide (MTT) assay. Expression of RASAL1 mRNA and its promoter region
      methylation were evaluated by real-time PCR and methylation-specific PCR. Effects
      of 5-AZA-dC on expression of alpha-SMA, fibronectin (FN), and TGF-beta receptor 2
      (TGF-beta R2) and Smad2/3 phosphorylation were analyzed by Western blotting.
      Effect of short interfering RNA (siRNA) knock-down of MeCP2 on expression of
      alpha-SMA and FN induced by TGFbeta was determined. RESULTS: MeCP2 was abundantly
      expressed in cells within PVR membranes where it was double labeled with cells
      positive for cytokeratin and alpha-SMA. 5-AZA-dC inhibited expression of MeCP2
      and suppressed RASAL1 gene methylation while increasing expression of the RASAL1
      gene. Treatment with 5-AZA-dC significantly suppressed the expression of alpha
      SMA, FN, TGF-beta R2 and phosphorylation of Smad2/3 and inhibited RPE cell
      migration. TGF-beta induced expression of alpha-SMA, and FN was suppressed by
      knock-down of MeCP2. CONCLUSIONS: MeCP2 and DNA methylation regulate RPE
      transdifferentiation and may be involved in the pathogenesis of PVR.

PMID- 26305532
TI  - Genetic Evidence for Differential Regulation of Corneal Epithelial and Stromal
      Thickness.
AB  - PURPOSE: Central corneal thickness (CCT) is a quantitative trait associated with
      keratoconus and primary open-angle glaucoma. Although CCT is highly heritable,
      known genetic variations explain only a fraction of the phenotypic variability.
      The purpose of this study was to identify additional CCT-influencing loci using
      inbred strains of mice. METHODS: Cohorts of 82 backcrossed (N2) and 99
      intercrossed (F2) mice were generated from crosses between recombinant inbred
      BXD24/TyJ and wild-derived CAST/EiJ mice. Using anterior chamber optical
      coherence tomography, mice were phenotyped at 10 to 12 weeks of age, genotyped
      based on 96 genome-wide single nucleotide polymorphisms (SNPs), and subjected to
      quantitative trait locus (QTL) analysis. RESULTS: In an analysis of total CCT
      among all mice, two loci passed the significance threshold of P = 0.05. These
      were on Chr 3 and Chr 11 (Cctq4 and Cctq5, respectively). A third locus of
      interest was identified in a two-dimensional pairwise analysis; this locus on Chr
      14 (Cctq6) exhibited a significant additive effect with Cctq5. Independent
      analyses of the dataset for epithelial and stromal thickness revealed that Cctq4
      is specific to the epithelial layer and that Cctq5 and Cctq6 are specific to the
      stromal layer. CONCLUSIONS: Our findings demonstrate a quantitative multigenic
      pattern of CCT inheritance in mice and identify three previously unrecognized CCT
      influencing loci: Cctq4, Cctq5, and Cctq6. This is the first demonstration that
      distinct layers of the cornea are under differential genetic control and
      highlights the need to refine the design of future genome-wide association
      studies of CCT.

PMID- 26305533
TI  - Genomic Copy Number Variations of the Complement Component C4B Gene Are
      Associated With Chronic Central Serous Chorioretinopathy.
AB  - PURPOSE: Chronic central serous chorioretinopathy (cCSC) has recently been
      associated to variants in the complement factor H gene. To further investigate
      the role of the complement system in cCSC, the genomic copy number variations in
      the complement component 4 gene (C4) were studied. METHODS: C4A and C4B copy
      numbers were analyzed in 197 cCSC patients and 303 healthy controls by using a
      Taqman copy number determination assay. Copy numbers of C4A, C4B, and the total
      C4 load were compared between cases and controls, by using a Fisher exact test.
      For this analysis Bonferroni correction was performed for three tests, and P
      values < 0.017 were considered to be significant. A logistic regression model was
      constructed to calculate the odds ratios (ORs) of each of the C4B copy numbers,
      using two copies as a reference. For this model P values < 0.05 were considered
      to be significant. RESULTS: C4B genomic copy numbers differed significantly
      between cCSC patients and healthy controls (P = 0.0018). Absence of C4B
      significantly conferred risk of cCSC (P = 0.039, OR = 2.61 [95% confidence
      interval (CI) = 1.05-6.52]), whereas three copies of C4B significantly decreased
      the risk of cCSC (P = 0.014, OR = 0.45 [95% CI = 0.23-0.85]). The C4A genomic
      copy numbers and total C4 load did not significantly differ between cases and
      controls. CONCLUSIONS: This study showed that copy numbers of C4B are
      significantly associated with cCSC. Carrying no copies of C4B significantly
      increases the risk of cCSC, whereas carrying three C4B copies is protective.
      These findings reinforce the hypothesis of a possible involvement of the
      complement system in the pathogenesis of cCSC.

PMID- 26305534
TI  - The Antioxidant N-Acetylcysteine Inhibits Inflammatory and Apoptotic Processes in
      Human Conjunctival Epithelial Cells in a High-Glucose Environment.
AB  - PURPOSE: We evaluated the effects of N-acetylcysteine (NAC), which is known to
      inhibit reactive oxygen species (ROS)-dependent apoptosis, on high glucose
      induced ROS, apoptosis, inflammation, and delayed-wounding closure in primary
      cultured human conjunctival epithelial cells (pHCECs), and the regulatory effects
      of cleaved caspase-3, BAX, nuclear factor kappaB (NF-kappaB), IL-6, and TNF-alpha
      on these processes. METHODS: High glucose-induced ROS generation was measured
      using 2',7'-dichlorofluorescein diacetate (DCFH-DA). The effects of NAC on high
      glucose-induced apoptosis were investigated in pHCECs using Annexin-V and PI
      staining, and cleaved caspase-3 and BAX expression levels using immunoblotting.
      To evaluate the inflammatory response, IL-6 and TNF-alpha expression levels were
      quantified by multiplex cytokine analysis, and NF-kappaB activation and IkB-alpha
      degradation were assessed by Western blot analysis. The effects of NAC on high
      glucose-delayed conjunctival epithelial wound healing were assessed by a scratch
      induced directional wounding assay. RESULTS: Compared to the untreated control
      and normal glucose (5 mM), high glucose at 25 mM stimulated ROS generation,
      apoptosis, and release of inflammatory cytokines, and delayed wound healing in
      pHCECs. The addition of NAC markedly reduced the high glucose-induced ROS
      activation, Annexin-PI-positive cells, and levels of cleaved caspase-3, BAX, IL
      6, and TNF-alpha. N-acetylcysteine also prevented high glucose-delayed wound
      healing. CONCLUSIONS: High glucose levels promote apoptosis by affecting
      mitochondria-dependent caspase activity through elevation of ROS production, a
      process that can be reversed by the antioxidant NAC. These findings demonstrate
      that NAC has a beneficial effect on conjunctival epithelial cell wound healing,
      antiapoptosis, and anti-inflammation in the conjunctival epithelial cell.

PMID- 26305535
TI  - The impact of change in serum C-reactive protein level on the prediction of
      effects of molecular targeted therapy in patients with metastatic renal cell
      carcinoma.
AB  - OBJECTIVES: To investigate the impact of pretreatment serum C-reactive protein
      (CRP) level and its change after targeted therapy on the anti-tumour effect of
      targeted agents in patients with metastatic renal cell carcinoma (mRCC). PATIENTS
      AND METHODS: The serum CRP level in 190 cases of molecular targeted therapy for
      mRCC was measured before starting the prescription of molecular targeted agents
      and when computed tomography showed the maximum effect. Patients in which the
      pretreatment CRP level was >=0.5 mg/dL were classified into a 'higher-CRP' group
      and others into a 'lower-CRP' group. The higher-CRP group was further classified
      into two subgroups, i.e. those whose serum CRP level decreased after molecular
      targeted therapy ('decreased-CRP' subgroup), and those whose level did not
      decrease after therapy ('non-decreased-CRP' subgroup). All patients were also
      classified according to their other clinical details and progression-free
      survival (PFS) rates of each subgroup were compared. RESULTS: Of the 190
      patients, 97 were categorised as lower CRP and 93 as higher CRP, with 50 and 43
      patients in the higher-CRP group further categorised as decreased- and non
      decreased-CRP subgroups, respectively. For the maximum effects of the targeted
      therapy, determined based on the Response Evaluation Criteria In Solid Tumors
      (RECIST) criteria, in the lower-CRP group, significantly more patients had a
      complete response (CR) and partial response (PR) (P = 0.002) and significantly
      fewer had progressive disease (PD) (P < 0.001) vs the higher-CRP group. In the
      higher-CRP group, significantly fewer patients had PD in the decreased-CRP
      subgroup (P < 0.001) than those in the non-decreased-CRP subgroup. The 2-year PFS
      rate for the lower-CRP group (39.1%) was significantly better vs the decreased
      CRP subgroup (21.2%; P = 0.013) and significantly better vs the non-decreased CRP
      subgroup (0%; P < 0.001). Multivariate analyses in the higher-CRP group revealed
      that decreased CRP was an independent predictive factor for PFS (P = 0.002,
      hazard ratio 2.454, 95% confidence interval 1.404-4.290). CONCLUSION: A decrease
      of CRP and pretreatment CRP levels show promise as a novel predictive factor for
      anti-tumour effects in patients treated with molecular targeted therapy.

PMID- 26305536
TI  - Regional Choroidal Thickness Changes in Branch Retinal Vein Occlusion with
      Macular Edema.
AB  - PURPOSE: To investigate regional changes in choroidal thickness in branch retinal
      vein occlusion (BRVO) patients with macular edema. METHODS: Choroidal thickness
      in the subfoveal, occlusive, and nonocclusive areas in BRVO eyes was measured
      using enhanced depth imaging by spectral domain optical coherence tomography. The
      choroidal thickness was compared with the corresponding values both in the fellow
      eye and in normal controls at baseline. Regional changes in choroidal thickness
      were then evaluated in the BRVO eyes after intravitreal bevacizumab (IVB)
      injections. RESULTS: Regional choroidal thickness was measured in 57 eyes at
      baseline. The mean choroidal thickness of the occlusive area was significantly
      higher than that of the nonocclusive, subfoveal, and corresponding areas in the
      fellow eyes and normal controls (p < 0.001). The choroidal thickness in the
      occlusive area correlated with the retinal thickness in both the central and
      occlusive areas (rho = 0.590, p < 0.001, and rho = 0.351, p = 0.011,
      respectively), but not with visual acuity. After IVB, the choroidal thickness in
      the occlusive area had decreased significantly (p = 0.004), but remained higher
      than that of other areas (p < 0.001 and p = 0.026). CONCLUSION: In acute BRVO
      eyes, the choroid is thicker in the occlusive area. This difference is correlated
      with the severity of macular edema, but not with visual acuity. Bevacizumab
      reduces choroidal thickness, but does not restore normal values.

PMID- 26305537
TI  - Perspectives on benefit-risk decision-making in vaccinology: Conference report.
AB  - Benefit/risk (B/R) assessment methods are increasingly being used by regulators
      and companies as an important decision-making tool and their outputs as the basis
      of communication. B/R appraisal of vaccines, as compared with drugs, is different
      due to their attributes and their use. For example, vaccines are typically given
      to healthy people, and, for some vaccines, benefits exist both at the population
      and individual level. For vaccines in particular, factors such as the benefit
      afforded through herd effects as a function of vaccine coverage and consequently
      impact the B/R ratio, should also be taken into consideration and parameterized
      in B/R assessment models. Currently, there is no single agreed methodology for
      vaccine B/R assessment that can fully capture all these aspects. The conference
      "Perspectives on Benefit-Risk Decision-making in Vaccinology," held in Annecy
      (France), addressed these issues and provided recommendations on how to advance
      the science and practice of B/R assessment of vaccines and vaccination programs. 

PMID- 26305538
TI  - Gamma regularization based reconstruction for low dose CT.
AB  - Reducing the radiation in computerized tomography is today a major concern in
      radiology. Low dose computerized tomography (LDCT) offers a sound way to deal
      with this problem. However, more severe noise in the reconstructed CT images is
      observed under low dose scan protocols (e.g. lowered tube current or voltage
      values). In this paper we propose a Gamma regularization based algorithm for LDCT
      image reconstruction. This solution is flexible and provides a good balance
      between the regularizations based on l0-norm and l1-norm. We evaluate the
      proposed approach using the projection data from simulated phantoms and scanned
      Catphan phantoms. Qualitative and quantitative results show that the Gamma
      regularization based reconstruction can perform better in both edge-preserving
      and noise suppression when compared with other norms. 

PMID- 26305539
TI  - Proteomic Analysis of Fetal Ovary Reveals That Ovarian Developmental Potential Is
      Greater in Meishan Pigs than in Yorkshire Pigs.
AB  - Time-dependent expression of functional proteins in fetal ovaries is important to
      understand the developmental process of the ovary. This study was carried out to
      enhance our understanding of the developmental process of porcine fetal ovaries
      and to better address the differences in fetal ovary development of local and
      foreign pigs. The objective of the present study is to test the expression of key
      proteins that regulate the growth and development of fetal ovaries in Meishan and
      Yorkshire porcine breeds by using proteomics technology. Six Meishan and 6
      Yorkshire pregnant gilts were used in this experiment. Fetal ovaries were
      obtained from Yorkshire and Meishan gilts on days 55 and 90 of the gestation
      period. Using 2D-DIGE (two dimensional-difference in gel electrophoresis)
      analysis, the results showed that there are about 1551 and 1400 proteins in gilt
      fetal ovaries on days 55 and 90, respectively of the gestation. Using MALDI TOF
      TOF MS analysis, 27 differentially expressed proteins were identified in the
      fetal ovaries of the 2 breeds on day 55 of gestation, and a total of 18 proteins
      were identified on day 90 of gestation. These differentially expressed proteins
      were involved in the regulation of biological processes (cell death, stress
      response, cytoskeletal proteins) and molecular functions (enzyme regulator
      activity). We also found that alpha-1-antitrypsin, actin, vimentin, and PP2A
      proteins promote the formation of primordial follicles in the ovaries of
      Yorkshire pigs on day 55 of gestation while low expression heat shock proteins
      and high expression alpha-fetoproteins (AFP) may promote Meishan fetal ovarian
      follicular development on day 90 of gestation. These findings provide a deeper
      understanding of how reduced expression of heat shock proteins and increased
      expression of AFP can significantly reduce the risk of reproductive disease in
      obese Meishan sows. Our study also shows how these proteins can increase the
      ovulation rate and may be responsible for the low reproductive efficiency
      reported in other obese breeds. The ovarian developmental potential was found to
      be greater in Meishan pigs than in Yorkshire pigs. 

PMID- 26305546
TI  - Activation of Mir-29a in Activated Hepatic Stellate Cells Modulates Its
      Profibrogenic Phenotype through Inhibition of Histone Deacetylases 4.
AB  - BACKGROUND: Recent studies have shown that microRNA-29 (miR-29) is significantly
      decreased in liver fibrosis and that its downregulation influences the activation
      of hepatic stellate cells (HSCs). In addition, inhibition of the activity of
      histone deacetylases 4 (HDAC4) has been shown to strongly reduce HSC activation
      in the context of liver fibrosis. OBJECTIVES: In this study, we examined whether
      miR-29a was involved in the regulation of HDAC4 and modulation of the
      profibrogenic phenotype in HSCs. METHODS: We employed miR-29a transgenic mice
      (miR-29aTg mice) and wild-type littermates to clarify the role of miR-29a in
      cholestatic liver fibrosis, using the bile duct-ligation (BDL) mouse model.
      Primary HSCs from both mice were treated with a miR-29a mimic and antisense
      inhibitor in order to analyze changes in profibrogenic gene expression and HSC
      activation using real-time quantitative RT-PCR, immunofluorescence staining,
      western blotting, and cell proliferation and migration assays. RESULTS: After
      BDL, overexpression of miR-29a decreased collagen-1alpha1, HDAC4 and activated
      HSC markers of glial fibrillary acidic protein expression in miR-29aTg mice
      compared to wild-type littermates. Overexpression of miR-29a and HDAC4 RNA
      interference decreased the expression of fibrotic genes, HDAC4 signaling, and HSC
      migration and proliferation. In contrast, knockdown of miR-29a with an antisense
      inhibitor increased HDAC4 function, restored HSC migration, and accelerated HSC
      proliferation. CONCLUSIONS: Our results indicate that miR-29a ameliorates
      cholestatic liver fibrosis after BDL, at least partially, by modulating the
      profibrogenic phenotype of HSCs through inhibition of HDAC4 function.

PMID- 26305547
TI  - Inhibition of Calcium-Activated Chloride Channel ANO1/TMEM16A Suppresses Tumor
      Growth and Invasion in Human Lung Cancer.
AB  - Lung cancer or pulmonary carcinoma is primarily derived from epithelial cells
      that are thin and line on the alveolar surfaces of the lung for gas exchange.
      ANO1/TMEM16A, initially identified from airway epithelial cells, is a member of
      Ca2+-activated Cl- channels (CaCCs) that function to regulate epithelial
      secretion and cell volume for maintenance of ion and tissue homeostasis.
      ANO1/TMEM16A has recently been shown to be highly expressed in several epithelium
      originated carcinomas. However, the role of ANO1 in lung cancer remains unknown.
      In this study, we show that inhibition of calcium-activated chloride channel
      ANO1/TMEM16A suppresses tumor growth and invasion in human lung cancer. ANO1 is
      upregulated in different human lung cancer cell lines. Knocking-down ANO1 by
      small hairpin RNAs inhibited proliferation, migration and invasion of GLC82 and
      NCI-H520 cancel cells evaluated by CCK-8, would-healing, transwell and 3D soft
      agar assays. ANO1 protein is overexpressed in 77.3% cases of human lung
      adenocarcinoma tissues detected by immunohistochemistry. Furthermore, the tumor
      growth in nude mice implanted with GLC82 cells was significantly suppressed by
      ANO1 silencing. Taken together, our findings provide evidence that ANO1
      overexpression contributes to tumor growth and invasion of lung cancer; and
      suppressing ANO1 overexpression may have therapeutic potential in lung cancer
      therapy. 

PMID- 26305548
TI  - Tumor necrosis targeted radiotherapy of non-small cell lung cancer using
      radioiodinated protohypericin in a mouse model.
AB  - Lung cancer is the leading cause of cancer-related death. About 80% of lung
      cancers are non-small cell lung cancers (NSCLC). Radiotherapy is widely used in
      treatment of NSCLC. However, the outcome of NSCLC remains unsatisfactory. In this
      study, a vascular disrupting agent (VDA) combretastatin-A4-phosphate (CA4P) was
      used to provide massive necrosis targets. (131)I labeled necrosis-avid agent
      protohypericin ((131)I-prohy) was explored for therapy of NSCLC using tumor
      necrosis targeted radiotherapy (TNTR). Gamma counting, autoradiography,
      fluorescence microscopy and histopathology were used for biodistribution
      analysis. Magnetic resonance imaging (MRI) was used to monitor tumor volume,
      ratios of necrosis and tumor doubling time (DT). The biodistribution data
      revealed 131I-prohy was delivered efficiently to tumors. Tracer uptake peaked at
      24 h in necrotic tumor of (131)I-prohy with and without combined CA4P (3.87 +/-
      0.38 and 2.96 +/- 0.34%ID/g). (131)I-prohy + CA4P enhanced the uptake of (131)I
      prohy in necrotic tumor compared to (131)I-prohy alone. The TNTR combined with
      CA4P prolonged survival of tumor bearing mice relative to vehicle control group,
      CA4P control group and (131)I-prohy control group with median survival of 35, 20,
      22 and 27 days respectively. In conclusion, TNTR appeared to be effective for the
      treatment of NSCLC.

PMID- 26305549
TI  - Tumor microenvironment B cells increase bladder cancer metastasis via modulation
      of the IL-8/androgen receptor (AR)/MMPs signals.
AB  - While B cells in the tumor microenvironment may play important roles in cancer
      progression, their impacts on the bladder cancer (BCa) metastasis remain unclear.
      Here we found from human clinical BCa samples that BCa tissues could recruit more
      B cells than the surrounding normal bladder tissues and the in vitro co-culture
      assay also demonstrated that B cells could be recruited more easily towards BCa
      cells compared to normal bladder cells. Chamber invasion and 3D invasion assays
      showed the recruited B cells could then significantly increase the BCa cell
      invasion. Mechanism dissection found that recruited B cells could increase IL
      8/androgen receptor (AR) signals in BCa cells that could then promote the
      expression of metastasis genes including MMP1 and MMP13. Blocking the IL
      8/AR/MMPs signals either by anti-IL-8 neutralizing antibody, AR-siRNA, or MMPs
      inhibitors all partially reversed the infiltrating B cells capacity to increase
      the BCa cell invasion. The in vivo data from orthotopically xenografted BCa mouse
      model also confirmed that infiltrating B cells could increase BCa cell invasion
      via increasing AR signals. Together, these results demonstrate the key roles of B
      cells within the bladder tumor microenvironment that increase the BCa metastasis
      and may help us to develop the potential therapies via targeting these newly
      identified IL-8/AR/MMPs signals to better battle the BCa progression. 

PMID- 26305550
TI  - Curcumin combined with FAPalphac vaccine elicits effective antitumor response by
      targeting indolamine-2,3-dioxygenase and inhibiting EMT induced by TNF-alpha in
      melanoma.
AB  - Fibroblast activation protein alpha (FAPalpha) is a potential target for cancer
      therapy. However, elimination of FAPalpha+ fibroblasts activates secretion of IFN
      gamma and TNF-alpha. IFN-gamma can in turn induce expression indolamine-2,3
      dioxygenase (IDO), thereby contributing to immunosuppression, while TNF-alpha can
      induce EMT. These two reactive effects would limit the efficacy of a tumor
      vaccine. We found that curcumin can inhibit IDO expression and TNF-alpha-induced
      EMT. Moreover, FAPalphac vaccine and CpG combined with curcumin lavage inhibited
      tumor growth and prolonged the survival of mice implanted with melanoma cells.
      The combination of FAPalphac vaccine, CpG and curcumin stimulated FAPalpha
      antibody production and CD8+ T cell-mediated killing of FAPalpha-expressing
      stromal cells without adverse reactive effects. We suggest a combination of
      curcumin and FAPalphac vaccine for melanoma therapy. 

PMID- 26305551
TI  - HIF isoforms have divergent effects on invasion, metastasis, metabolism and
      formation of lipid droplets.
AB  - Cancer cells adapt to hypoxia by the stabilization of hypoxia inducible factor
      (HIF)-alpha isoforms that increase the transcription of several genes. Among the
      genes regulated by HIF are enzymes that play a role in invasion, metastasis and
      metabolism. We engineered triple (estrogen receptor/progesterone
      receptor/HER2/neu) negative, invasive MDA-MB-231 and SUM149 human breast cancer
      cells to silence the expression of HIF-1alpha, HIF-2alpha or both isoforms of HIF
      alpha. We determined the metabolic consequences of HIF silencing and the ability
      of HIF-alpha silenced cells to invade and degrade the extracellular matrix (ECM)
      under carefully controlled normoxic and hypoxic conditions. We found that
      silencing HIF-1alpha alone was not sufficient to attenuate invasiveness in both
      MDA-MB-231 and SUM149 cell lines. Significantly reduced metastatic burden was
      observed in single (HIF-1alpha or HIF-2alpha) and double alpha-isoform silenced
      cells, with the reduction most evident when both HIF-1alpha and HIF-2alpha were
      silenced in MDA-MB-231 cells. HIF-2alpha played a major role in altering cell
      metabolism. Lipids and lipid droplets were significantly reduced in HIF-2alpha
      and double silenced MDA-MB-231 and SUM149 cells, implicating HIF in their
      regulation. In addition, lactate production and glucose consumption were reduced.
      These results suggest that in vivo, cells in or near hypoxic regions are likely
      to be more invasive. The data indicate that targeting HIF-1alpha alone is not
      sufficient to attenuate invasiveness, and that both HIF-1alpha and HIF-2alpha
      play a role in the metastatic cascade in these two cell lines. 

PMID- 26305552
TI  - Zoledronic acid prevents the tumor-promoting effects of mesenchymal stem cells
      via MCP-1 dependent recruitment of macrophages.
AB  - Zoledronic acid (ZA) has been tested in clinical trials as an additive therapy
      for early-stage breast cancer. However, the mechanism by which ZA exerts its
      antitumor activity is still unclear. The aim of this study is to investigate
      whether the prevention of tumor growth by ZA is through regulating the
      mesenchymal stem cells (MSC)-monocyte chemotactic protein 1 (MCP-1)-macrophages
      axis in the tumor microenvironment. To address this issue, MDA-MB-231-FLUC human
      breast cancer cells were cultured and injected either alone, or coupled with MSC
      into the mammary fat pads of nude mice. MSC were treated with either ZA or
      untreated. Tumor growth was determined by using an in vivo bioluminescence
      imaging (BLI) and the tumor-associated macrophages (TAMs) in tumor tissues were
      immunohistochemically analyzed by using CD206 antibody. The effects of ZA on the
      cytokine related gene expression of MSC were assessed by using real-time PCR. In
      this study, we found that ZA-treated mice showed a significant delay in tumor
      growth. In addition, our data revealed that ZA weakened the ability of MSC to
      promote tumor growth by impairing TAMs recruitment and tumor vascularization.
      Furthermore, it was found that ZA decreased MCP-1 expression of MSC, and
      therefore reduced the recruitment of TAMs to the tumor sites and hence inhibited
      the tumor growth. Altogether, our study demonstrated ZA can prevent the tumor
      promoting effects of MSC. The antitumor effects of ZA were caused by decreasing
      the MCP-1 expression of MSC, which further decreased the infiltration of TAMs
      into tumor sites, and therefore inhibited the tumor growth. 

PMID- 26305553
TI  - Histone Deacetylase 3 and 4 Complex Stimulates the Transcriptional Activity of
      the Mineralocorticoid Receptor.
AB  - Histone deacetylases (HDACs) act as corepressors in gene transcription by
      altering the acetylation of histones, resulting in epigenetic gene silencing. We
      previously reported that HDAC3 acts as a coactivator of the mineralocorticoid
      receptor (MR). Although HDAC3 forms complexes with class II HDACs, their
      potential role in the transcriptional activity of MR is unclear. We hypothesized
      that HDAC4 of the class II family stimulates the transcriptional activity of MR.
      The expression of MR target genes was measured by quantitative real-time PCR. MR
      and RNA polymerase II recruitment to promoters of MR target genes was analyzed by
      chromatin immunoprecipitation. The association of MR with HDACs was investigated
      by co-immunoprecipitation. MR acetylation was determined with an anti-acetyl
      lysine antibody after immunoprecipitation with an anti-MR antibody. Among the
      class II HDACs, HDAC4 interacted with both MR and HDAC3 after aldosterone
      stimulation. The nuclear translocation of HDAC4 was mediated by protein kinase A
      (PKA) and protein phosphatases (PP). The transcriptional activity of MR was
      significantly decreased by inhibitors of PKA (H89), PP1/2 (calyculin A), class I
      HDACs (MS-275), but not class II HDACs (MC1568). MR acetylation was increased by
      H89, calyculin A, and MS-275, but not by MC1568. Interaction between MR and HDAC3
      was significantly decreased by H89, calyculin A, and HDAC4 siRNA. A non-genomic
      effect of MR via PKA and PP1/2 induced nuclear translocation of HDAC4 to
      facilitate the interaction between MR and HDAC3. Thus, we have uncovered a
      crucial role for a class II HDAC in the activation of MR-dependent transcription.

PMID- 26305554
TI  - Experimental and Analytical Comparisons of Tissue Dielectric Constant (TDC) and
      Bioimpedance Spectroscopy (BIS) in Assessment of Early Arm Lymphedema in Breast
      Cancer Patients after Axillary Surgery and Radiotherapy.
AB  - BACKGROUND: Early diagnosis of breast cancer treatment-related lymphedema (BCRL)
      is of great importance for longstanding treatment results. Tissue dielectric
      constant (TDC) and bioimpedance spectroscopy (BIS) both have a potential for
      early diagnosis, but have not been compared. METHODS AND RESULTS: One hundred
      women, treated for breast cancer with breast surgery, axillary dissection, and
      radiotherapy, were examined within one year after breast cancer treatment, as
      part of the follow-up procedure. Affected/at-risk and contralateral arms were
      measured with the TDC technique specific to localized skin water content and the
      BIS technique assessing arm extracellular fluid (ECF). Thirty-eight patients were
      clinically diagnosed for lymphedema (38.0%). The sensitivity and specificity for
      the TDC method were 65.8% and 83.9%, and for BIS method 42.1% and 93.5%, (p <
      0.001 and NS), respectively. Of all lymphedema, 18.4% were detected only by TDC
      and 2.6% by BIS. Affected arm to contralateral arm TDC ratios for upper arm and
      forearm, 1.56 +/- 0.49 and 1.28 +/- 0.33, demonstrating the localized feature of
      the TDC measurements were significantly greater than the BIS arm ratio 1.12 +/-
      0.12 (both p < 0.001). CONCLUSIONS: Discrepancies between TDC and BIS techniques
      in assessing lymphedema are related to different measurement techniques and
      assessed tissue water components. Independently of selected technique-specific
      threshold limit, the TDC technique was more sensitive than the BIS technique in
      the early assessment of BCRL and demonstrated that nearly 20% of early lymphedema
      are only superficially localized. The results further supported the complementary
      role of TDC and arm volume measurements as a highly diagnostic method for early
      lymphedema.

PMID- 26305556
TI  - Correction: MicroRNA-330-5p as a Putative Modulator of Neoadjuvant
      Chemoradiotherapy Sensitivity in Oesophageal Adenocarcinoma.

PMID- 26305555
TI  - Combined Antiviral Therapy Using Designed Molecular Scaffolds Targeting Two
      Distinct Viral Functions, HIV-1 Genome Integration and Capsid Assembly.
AB  - Designed molecular scaffolds have been proposed as alternative therapeutic agents
      against HIV-1. The ankyrin repeat protein (Ank(GAG)1D4) and the zinc finger
      protein (2LTRZFP) have recently been characterized as intracellular antivirals,
      but these molecules, used individually, do not completely block HIV-1 replication
      and propagation. The capsid-binder Ank(GAG)1D4, which inhibits HIV-1 assembly,
      does not prevent the genome integration of newly incoming viruses. 2LTRZFP,
      designed to target the 2-LTR-circle junction of HIV-1 cDNA and block HIV-1
      integration, would have no antiviral effect on HIV-1-infected cells. However,
      simultaneous expression of these two molecules should combine the advantage of
      preventive and curative treatments. To test this hypothesis, the genes encoding
      the N-myristoylated Myr(+)Ank(GAG)1D4 protein and the 2LTRZFP were introduced
      into human T-cells, using a third-generation lentiviral vector. SupT1 cells
      stably expressing 2LTRZFP alone or with Myr(+)Ank(GAG)1D4 showed a complete
      resistance to HIV-1 in viral challenge. Administration of the Myr(+)Ank(GAG)1D4
      vector to HIV-1-preinfected SupT1 cells resulted in a significant antiviral
      effect. Resistance to viral infection was also observed in primary human CD4+ T
      cells stably expressing Myr(+)Ank(GAG)1D4, and challenged with HIV-1, SIVmac, or
      SHIV. Our data suggest that our two anti-HIV-1 molecular scaffold prototypes are
      promising antiviral agents for anti-HIV-1 gene therapy. 

PMID- 26305557
TI  - Beneficial Effect of Etanercept on Hyperoxic Lung Injury Model in Neonatal Rats.
AB  - PURPOSE: To determine whether prophylaxis with etanercept, an anti-inflammatory
      drug, would decrease the severity of lung injury in a neonatal rat model of
      bronchopulmonary dysplasia (BPD); MATERIALS AND METHODS: Rat pups were divided
      into three groups: pups exposed to room air (group 1; n = 10), to hyperoxia +
      placebo (group 2; n = 9), and to hyperoxia + etanercept (group 3; n = 8). Lung
      morphology was assessed by alveolar surface area percentage, which is a measure
      of alveolar size. The severities of lung inflammation and antioxidant capacity
      were assessed by quantifying tumor necrosis factor-alpha (TNF-alpha),
      transforming growth factor-beta (TGF-beta), malondialdehyde (MDA), and superoxide
      dismutase (SOD) from lung homogenate; RESULTS: The percentage of alveolar surface
      areas were significantly higher in group 3 compared to group 2 (p = .004) and
      similar in both group 1 and group 3 (p = .21). The mean level of lung MDA was
      significantly higher in group 2 compared to group 1 and group 3 (p < .05 for
      both). Lung homogenate SOD activities in group 3 was significantly higher than
      group 2 (p < .001). Furthermore, group 3 pups had lower levels of TNF-alpha and
      TGF-beta in lung homogenate than that in group 2 (p < .05 for both) but similar
      in both group 1 and group 3; CONCLUSION: Etanercept has favorable effects on
      alveolarization as well as inflammation and oxidative stress markers in a
      neonatal rat model of BPD.

PMID- 26305558
TI  - Evidence for Retromutagenesis as a Mechanism for Adaptive Mutation in Escherichia
      coli.
AB  - Adaptive mutation refers to the continuous outgrowth of new mutants from a non
      dividing cell population during selection, in apparent violation of the neo
      Darwinian principle that mutation precedes selection. One explanation is that of
      retromutagenesis, in which a DNA lesion causes a transcriptional mutation that
      yields a mutant protein, allowing escape from selection. This enables a round of
      DNA replication that establishes heritability. Because the model requires that
      gene expression precedes DNA replication, it predicts that during selection, new
      mutants will arise from damage only to the transcribed DNA strand. As a test, we
      used a lacZ amber mutant of Escherichia coli that can revert by nitrous acid
      induced deamination of adenine residues on either strand of the TAG stop codon,
      each causing different DNA mutations. When stationary-phase, mutagenized cells
      were grown in rich broth before being plated on lactose-selective media, only non
      transcribed strand mutations appeared in the revertants. This result was
      consistent with the known high sensitivity to deamination of the single-stranded
      DNA in a transcription bubble, and it provided an important control because it
      demonstrated that the genetic system we would use to detect transcribed-strand
      mutations could also detect a bias toward the non-transcribed strand. When
      residual lacZ transcription was blocked beforehand by catabolite repression, both
      strands were mutated about equally, but if revertants were selected immediately
      after nitrous acid exposure, transcribed-strand mutations predominated among the
      revertants, implicating retromutagenesis as the mechanism. This result was not
      affected by gene orientation. Retromutagenesis is apt to be a universal method of
      evolutionary adaptation, which enables the emergence of new mutants from
      mutations acquired during counterselection rather than beforehand, and it may
      have roles in processes as diverse as the development of antibiotic resistance
      and neoplasia. 

PMID- 26305560
TI  - Limitation of the activated partial thromboplastin time as a monitoring method of
      the direct thrombin inhibitor argatroban.
AB  - BACKGROUND: Argatroban is licensed for patients with heparin-induced
      thrombocytopenia and monitoring is conventionally by activated partial
      thromboplastin time (APTT) ratio with a target of 1.5-3.0 and not exceeding 100
      s. The APTT may be influenced by coagulopathies, lupus anticoagulant and raised
      FVIII levels. Variable but not clinically significant sensitivity of APTT
      reagents to argatroban has been highlighted in other studies. METHODS: Residual
      plasma of 15 patients (n = 124 samples) was tested on Sysmex(TM) CS series using
      the Hemoclot((r)) thrombin inhibitor assay (HTI) and APTT ratio (Actin FS and
      SynthASil). A subgroup from four patients (n = 31) were tested on ACL TOP(TM) to
      compare the different platforms with the HTI. Spiked normal pooled plasma was
      tested with Actin FS, Actin FSL, SynthASil and APTT-SP on their respective
      platforms (CS5100(TM) and ACL TOP(TM)) to assess reagent sensitivity. RESULTS:
      Mean concentration of argatroban by HTI assay for patient plasma was 0.47 MUg/mL;
      the mean APTT ratio using Actin FS was 1.89 and for SynthASil 1.56. There was a
      poor correlation between APTT and the HTI. In the spiked normal pooled plasma,
      Actin FS gave a significantly higher APTT ratio than the other three reagents for
      the various argatroban concentrations. CONCLUSIONS: Hemoclot((r)) thrombin
      inhibitor assay should be considered in patients on argatroban, particularly if
      there is concern the APTT may not be reflective of the degree of anticoagulation
      with argatroban due to other factors including coagulopathies in critically ill
      patients, the presence of a lupus anticoagulant or very high FVIII levels.

PMID- 26305559
TI  - Social Support and Health in Diabetes Patients: An Observational Study in Six
      European Countries in an Era of Austerity.
AB  - INTRODUCTION: Support from individual social networks, community organizations
      and neighborhoods is associated with better self-management and health outcomes.
      This international study examined the relative impact of different types of
      support on health and health-related behaviors in patients with type 2 diabetes.
      METHODS: Observational study (using interviews and questionnaires) in a sample of
      1,692 type 2 diabetes patients with 5,433 connections from Bulgaria, Greece,
      Netherlands, Norway, Spain, and the United Kingdom. Outcomes were patient
      reported health status (SF-12), physical exercise (RAPA), diet and smoking
      (SDCSCA). Random coefficient regression models were used to examine linkages with
      individual networks, community organizations, and neighborhood type (deprived
      rural, deprived urban, or affluent urban). RESULTS: Patients had a median of 3
      support connections and 34.6% participated in community organizations. Controlled
      for patients' age, sex, education, income and comorbidities, large emotional
      support networks were associated with decrease of non-smoking (OR = 0.87). Large
      practical support networks were associated with worse physical and mental health
      (B = -0.46 and -0.27 respectively) and less physical activity (OR = 0.90).
      Participation in community organizations was associated with better physical and
      mental health (B = 1.39 and 1.22, respectively) and, in patients with low income,
      with more physical activity (OR = 1.53). DISCUSSION: Participation in community
      organizations was most consistently related to better health status. Many
      diabetes patients have individual support networks, but this study did not
      provide evidence to increase their size as a public health strategy. The
      consistent association between participation in community organizations and
      health status provides a clear target for interventions and policies.

PMID- 26305561
TI  - Tapetal oleosins play an essential role in tapetosome formation and protein
      relocation to the pollen coat.
AB  - The Arabidopsis pollen grain is covered by a lipidic pollen coat representing
      select constituents released upon the programmed cell death of the anther
      secretory tapetum. These constituents originate primarily from two specialized
      tapetal organelles, elaioplasts and tapetosomes. Tapetosomes are distinctive
      Brassicaceae organelles derived from the endoplasmic reticulum that store
      triacylglycerols, flavonoids, alkanes, and proteins. The tapetosome
      triacylglycerols are found within lipid droplets surrounded by the highly
      variable tapetal oleosins that eventually generate the most abundant proteins of
      the pollen coat. Many questions remain regarding the sub-cellular targeting of
      tapetal oleosins as well as their role in tapetosome formation. Translational
      fusions of different tapetal oleosins or their derived domains to marker proteins
      were introduced into Arabidopsis thaliana to investigate their localization,
      processing and function. Arabidopsis tapetal oleosins were shown to be
      proteolytically cleaved following tapetum degeneration and different protein
      domains were targeted to the pollen coat despite vast differences in composition
      and size. Importantly, specific fusions were discovered to affect distinct
      aspects of tapetosome formation. This report not only highlighted the critical
      role of individual tapetal oleosin domains in Arabidopsis tapetosome formation,
      but revealed translational fusions to be a valuable tool in deciphering this
      evidently complex developmental process. 

PMID- 26305562
TI  - Case Report: No Response to Liposomal Daunorubicin in a Patient with Drug
      Resistant HIV-Associated Visceral Leishmaniasis.
AB  - Visceral leishmaniasis (VL) in patients with HIV co-infection presents a
      significant therapeutic challenge due to the lessened chance of achieving long
      term cure. We report a case of VL in a 60-year-old man with HIV infection who
      became refractory to anti-leishmania treatment due to multi-drug resistance. In
      the face of a worsening clinical situation, and with no other options available,
      he was treated with an experimental regimen of liposomal daunorubicin, which has
      previously been shown to have in vitro activity against Leishmania donovani and
      to be effective treatment of VL in animal studies. To our knowledge, he was the
      first patient with VL and HIV co-infection to have this treatment evaluated. We
      report on the lack of response to this treatment and possible causes for its
      failure. 

PMID- 26305563
TI  - A Preliminary Genetic Analysis of Complement 3 Gene and Schizophrenia.
AB  - Complement pathway activation was found to occur frequently in schizophrenia, and
      complement 3 (C3) plays a major role in this process. Previous studies have
      provided evidence for the possible role of C3 in the development of
      schizophrenia. In this study, we hypothesized that the gene encoding C3 (C3) may
      confer susceptibility to schizophrenia in Han Chinese. We analyzed 7 common
      single nucleotide polymorphisms (SNPs) of C3 in 647 schizophrenia patients and
      687 healthy controls. Peripheral C3 mRNA expression level was measured in 23 drug
      naive patients with schizophrenia and 24 controls. Two SNPs (rs1047286 and
      rs2250656) that deviated from Hardy-Weinberg equilibrium were excluded for
      further analysis. Among the remaining 5 SNPs, there was no significant difference
      in allele and genotype frequencies between the patient and control groups.
      Logistic regression analysis showed no significant SNP-gender interaction in
      either dominant model or recessive model. There was no significant difference in
      the level of peripheral C3 expression between the drug-naive schizophrenia
      patients and healthy controls. In conclusion, the results of this study do not
      support C3 as a major genetic susceptibility factor in schizophrenia. Other
      factors in AP may have critical roles in schizophrenia and be worthy of further
      investigation. 

PMID- 26305564
TI  - Transcriptome Profiling and Molecular Pathway Analysis of Genes in Association
      with Salinity Adaptation in Nile Tilapia Oreochromis niloticus.
AB  - Nile tilapia Oreochromis niloticus is a freshwater fish but can tolerate a wide
      range of salinities. The mechanism of salinity adaptation at the molecular level
      was studied using RNA-Seq to explore the molecular pathways in fish exposed to 0,
      8, or 16 (practical salinity unit, psu). Based on the change of gene expressions,
      the differential genes unions from freshwater to saline water were classified
      into three categories. In the constant change category (1), steroid biosynthesis,
      steroid hormone biosynthesis, fat digestion and absorption, complement and
      coagulation cascades were significantly affected by salinity indicating the
      pivotal roles of sterol-related pathways in response to salinity stress. In the
      change-then-stable category (2), ribosomes, oxidative phosphorylation, signaling
      pathways for peroxisome proliferator activated receptors, and fat digestion and
      absorption changed significantly with increasing salinity, showing sensitivity to
      salinity variation in the environment and a responding threshold to salinity
      change. In the stable-then-change category (3), protein export, protein
      processing in endoplasmic reticulum, tight junction, thyroid hormone synthesis,
      antigen processing and presentation, glycolysis/gluconeogenesis and
      glycosaminoglycan biosynthesis-keratan sulfate were the significantly changed
      pathways, suggesting that these pathways were less sensitive to salinity
      variation. This study reveals fundamental mechanism of the molecular response to
      salinity adaptation in O. niloticus, and provides a general guidance to
      understand saline acclimation in O. niloticus.

PMID- 26305566
TI  - Correction: Population Dynamics of a Salmonella Lytic Phage and Its Host:
      Implications of the Host Bacterial Growth Rate in Modelling.

PMID- 26305565
TI  - Pre-Pregnancy BMI, Gestational Weight Gain, and the Risk of Hypertensive
      Disorders of Pregnancy: A Cohort Study in Wuhan, China.
AB  - BACKGROUND: Hypertensive disorders of pregnancy (HDP) are major causes of
      maternal death worldwide and the risk factors are not fully understood. Few
      studies have investigated the risk factors for HDP among Chinese women. A cohort
      study involving 84,656 women was conducted to investigate pre-pregnancy BMI,
      total gestational weight gain (GWG), and GWG during early pregnancy as risk
      factors for HDP among Chinese women. METHODS: The study was conducted between
      2011-2013 in Wuhan, China, utilizing data from the Maternal and Children
      Healthcare Information Tracking System of Wuhan. A total of 84,656 women with a
      live singleton pregnancy were included. Multiple unconditional logistic
      regression was conducted to evaluate associations between putative risk factors
      and HDP. RESULTS: Women who were overweight or obese before pregnancy had an
      elevated risk of developing HDP (overweight: OR = 2.66, 95% CI = 2.32-3.05;
      obese: OR = 5.53, 95% CI = 4.28-7.13) compared to their normal weight
      counterparts. Women with total GWG above the Institute of Medicine (IOM)
      recommendation had an adjusted OR of 1.72 (95% CI = 1.54-1.93) for HDP compared
      to women who had GWG within the IOM recommendation. Women with gestational BMI
      gain >10 kg/m2 during pregnancy had an adjusted OR of 3.35 (95% CI = 2.89-3.89)
      for HDP, compared to women with a gestational BMI gain <5 kg/m2. The increased
      risk of HDP was also observed among women with higher early pregnancy (up to 18
      weeks of pregnancy) GWG (>600g/wk: adjusted OR = 1.48, 95% CI = 1.19-1.84).
      CONCLUSION: The results from this study show that maternal pre-pregnancy BMI,
      early GWG, and total GWG are positively associated with the risk of HDP. Weight
      control efforts before and during pregnancy may help to reduce the risk of HDP.

PMID- 26305567
TI  - Diet and nutrient intakes in urban women of Rajasthan State, Northern India.
AB  - Dietary and nutrient intakes of adult women have not been studied extensively
      which may contribute in increasing burden of morbidity and mortality in women.
      Present study assessed the diet and nutrient intake of women in the age group of
      35 -70 years. Door to door personal contact was done with women in identified
      locations and background was elicited using a questionnaire. Average intake of
      different foods and nutrients were recorded using semi quantitative FFQ and
      compared with Indian standards. Results revealed that average cereal, pulse,
      fruits, and vegetable intakes were below recommendations. Both energy and protein
      intakes were inadequate among subjects. Total fat, SAFA, and TFA intakes were
      higher and PUFA, MUFA, fibre, dietary iron, and folic acid intakes were lower
      than the recommendations. It was concluded that high fat intake and low fibre,
      PUFA, MUFA, iron, and folic acid intake may prone this community to diet-related
      chronic diseases. 

PMID- 26305568
TI  - Comparison of Nine Statistical Model Based Warfarin Pharmacogenetic Dosing
      Algorithms Using the Racially Diverse International Warfarin Pharmacogenetic
      Consortium Cohort Database.
AB  - OBJECTIVE: Multiple linear regression (MLR) and machine learning techniques in
      pharmacogenetic algorithm-based warfarin dosing have been reported. However,
      performances of these algorithms in racially diverse group have never been
      objectively evaluated and compared. In this literature-based study, we compared
      the performances of eight machine learning techniques with those of MLR in a
      large, racially-diverse cohort. METHODS: MLR, artificial neural network (ANN),
      regression tree (RT), multivariate adaptive regression splines (MARS), boosted
      regression tree (BRT), support vector regression (SVR), random forest regression
      (RFR), lasso regression (LAR) and Bayesian additive regression trees (BART) were
      applied in warfarin dose algorithms in a cohort from the International Warfarin
      Pharmacogenetics Consortium database. Covariates obtained by stepwise regression
      from 80% of randomly selected patients were used to develop algorithms. To
      compare the performances of these algorithms, the mean percentage of patients
      whose predicted dose fell within 20% of the actual dose (mean percentage within
      20%) and the mean absolute error (MAE) were calculated in the remaining 20% of
      patients. The performances of these techniques in different races, as well as the
      dose ranges of therapeutic warfarin were compared. Robust results were obtained
      after 100 rounds of resampling. RESULTS: BART, MARS and SVR were statistically
      indistinguishable and significantly out performed all the other approaches in the
      whole cohort (MAE: 8.84-8.96 mg/week, mean percentage within 20%: 45.88%-46.35%).
      In the White population, MARS and BART showed higher mean percentage within 20%
      and lower mean MAE than those of MLR (all p values < 0.05). In the Asian
      population, SVR, BART, MARS and LAR performed the same as MLR. MLR and LAR
      optimally performed among the Black population. When patients were grouped in
      terms of warfarin dose range, all machine learning techniques except ANN and LAR
      showed significantly higher mean percentage within 20%, and lower MAE (all p
      values < 0.05) than MLR in the low- and high- dose ranges. CONCLUSION: Overall,
      machine learning-based techniques, BART, MARS and SVR performed superior than MLR
      in warfarin pharmacogenetic dosing. Differences of algorithms' performances exist
      among the races. Moreover, machine learning-based algorithms tended to perform
      better in the low- and high- dose ranges than MLR.

PMID- 26305569
TI  - Multiscale Control of Hierarchical Structure in Crystalline Block Copolymer
      Nanoparticles Using Microfluidics.
AB  - Hierarchical semicrystalline block copolymer nanoparticles are produced in a
      segmented gas-liquid microfluidic reactor with top-down control of multiscale
      structural features, including nanoparticle morphologies, sizes, and internal
      crystallinities. Control of multiscale structure on disparate length scales by a
      single control variable (flow rate) enables tailoring of drug delivery
      nanoparticle function including release rates. 

PMID- 26305571
TI  - The Need for Evolutionarily Rational Disease Interventions: Vaccination Can
      Select for Higher Virulence.
AB  - There is little doubt evolution has played a major role in preventing the control
      of infectious disease through antibiotic and insecticide resistance, but recent
      theory suggests disease interventions such as vaccination may lead to evolution
      of more harmful parasites. A new study published in PLOS Biology by Andrew Read
      and colleagues shows empirically that vaccination against Marek's disease has
      favored higher virulence; without intervention, the birds die too quickly for any
      transmission to occur, but vaccinated hosts can both stay alive longer and shed
      the virus. This is an elegant empirical demonstration of how evolutionary theory
      can predict potentially dangerous responses of infectious disease to human
      interventions. 

PMID- 26305570
TI  - Effect of Chronic Blood Transfusion on Biomarkers of Coagulation Activation and
      Thrombin Generation in Sickle Cell Patients at Risk for Stroke.
AB  - Hypercoagulability in sickle cell disease (SCD) is associated with multiple SCD
      phenotypes, association with stroke risk has not been well described. We
      hypothesized that serum levels of biomarkers of coagulation activation correlate
      with high transcranial Doppler ultrasound velocity and decreases with blood
      transfusion therapy in SCD patients. Stored serum samples from subjects in the
      Stroke Prevention in Sickle Cell Anemia (STOP) trial were analyzed using ELISA
      and protein multiplexing techniques. 40 subjects from each treatment arm
      (Standard Care [SC] and Transfusion [Tx]) at three time points--baseline, study
      exit and one year post-trial and 10 each of age matched children with SCD but
      normal TCD (SNTCD) and with normal hemoglobin (HbAA) were analyzed. At baseline,
      median vWF, TAT and D-dimer levels were significantly higher among STOP subjects
      than either HbAA or SNTCD. At study exit, median hemoglobin level was
      significantly higher while median TCD velocity was significantly lower in Tx
      compared to SC subjects. Median vWF (409.6 vs. 542.9 MUg/ml), TAT (24.8 vs. 40.0
      ng/ml) and D-dimer (9.2 vs. 19.1 MUg/ml) levels were also significantly lower in
      the Tx compared to the SC group at study exit. Blood levels of biomarkers
      coagulation activation/thrombin generation correlated positively with TCD
      velocity and negatively with number of blood transfusions. Biomarkers of
      coagulation activation/thrombin generation were significantly elevated in
      children with SCD, at high risk for stroke. Reduction in levels of these
      biomarkers correlated with reduction in stroke risk (lower TCD velocity),
      indicating a possible role for hypercoagulation in SCD associated stroke.

PMID- 26305572
TI  - Janus Solid-Liquid Interface Enabling Ultrahigh Charging and Discharging Rate for
      Advanced Lithium-Ion Batteries.
AB  - LiFePO4 has long been held as one of the most promising battery cathode for its
      high energy storage capacity. Meanwhile, although extensive studies have been
      conducted on the interfacial chemistries in Li-ion batteries,1-3 little is known
      on the atomic level about the solid-liquid interface of LiFePO4/electrolyte.
      Here, we report battery cathode consisted with nanosized LiFePO4 particles in
      aqueous electrolyte with an high charging and discharging rate of 600 C (3600/600
      = 6 s charge time, 1 C = 170 mAh g(-1)) reaching 72 mAh g(-1) energy storage (42%
      of the theoretical capacity). By contrast, the accessible capacity sharply
      decreases to 20 mAh g(-1) at 200 C in organic electrolyte. After a comprehensive
      electrochemistry tests and ab initio calculations of the LiFePO4-H2O and LiFePO4
      EC (ethylene carbonate) systems, we identified the transient formation of a Janus
      hydrated interface in the LiFePO4-H2O system, where the truncated symmetry of
      solid LiFePO4 surface is compensated by the chemisorbed H2O molecules, forming a
      half-solid (LiFePO4) and half-liquid (H2O) amphiphilic coordination environment
      that eases the Li desolvation process near the surface, which makes a fast Li-ion
      transport across the solid/liquid interfaces possible. 

PMID- 26305573
TI  - Examining the association between early life social adversity and BMI changes in
      childhood: a life course trajectory analysis.
AB  - BACKGROUND: A number of studies have found associations between multiple aspects
      of social adversity and obesity in childhood, yet this research has largely been
      limited to cross-sectional data. OBJECTIVES: This study aimed to address this
      limitation by using life course trajectory methods to determine whether multiple
      aspects of social adversity in early childhood are associated with changes in
      body mass index (BMI) throughout childhood. METHODS: Associations between
      multiple measures of social adversity from birth to 4 years and subsequent BMI
      trajectories to age 17 were examined in 7021 children in the Avon Longitudinal
      Study of Parents and Children. RESULTS: Higher BMI throughout ages 12-17 were
      observed for children whose parents had separated, were exposed to frequent
      residential mobility or who experienced moderate or great household financial
      difficulty in early childhood. After adjustment for confounding variables,
      associations were attenuated but remained for both moderate (two moves) and high
      (>=3 moves) residential mobility (mean % difference in BMI at age 17 for children
      experiencing moderate and high residential mobility before age 4 compared with
      those experiencing no moves: 2.3; 95% CI: 0.5-4.2; P = 0.015 and 4.2; 95% CI: 1.4
      7.0; P = 0.004, respectively). CONCLUSIONS: Associations between BMI and social
      adversity in childhood are present but largely explained by background
      socioeconomic position. However, there remain small but important differences
      between the BMI of children who are exposed to frequent residential mobility in
      early childhood after adjustment for socioeconomic and other confounders.

PMID- 26305574
TI  - Laterality effects in cross-modal affective priming.
AB  - The present study pursued M. P. Bryden's legacy by investigating how contextual
      factors can affect laterality effects. Specifically, a cross-modal affective
      priming paradigm was used in two experiments to determine whether priming with
      facial expressions would affect responses to emotional sounds. Experiment 1
      established that cross-modal priming could be obtained when presenting the
      emotional sounds binaurally by showing more accurate responses when prime and
      target were congruent than when they were incongruent, although this extended to
      response time only for the happy emotion. This priming effect justified
      Experiment 2, in which the priming paradigm was integrated into a dichotic
      listening task. The central finding of Experiment 2 was a congruency by ear
      interaction on number of correct reports, showing that presentation of a facial
      emotion congruent with a left target produced a large left ear advantage that was
      reduced when a right ear congruent prime or an incongruent pairing was used.
      Implications of these findings for emotion processing in the context of Bryden's
      legacy are discussed.

PMID- 26305576
TI  - Nanopore-based electrical and label-free sensing of enzyme activity in blood
      serum.
AB  - A generic strategy to expand the analytical scope of electrical nanopore sensing
      is presented. We specifically and electrically detect the activity of a
      diagnostically relevant hydrolytic enzyme and remove the analytically harmful
      interference from the biochemically complex sample matrix of blood serum. Our
      strategy is demonstrated at the example of the renin protease which is involved
      in regulation of blood pressure. The analysis scheme exploits a new approach to
      reduce sample complexity while generating a specific read-out signal. Within a
      single spin-column (i), the protease cleaves a resin-tethered peptide substrate
      (ii) which is affinity-purified using the same multifunctional resin to remove
      interfering blood serum components, followed by (iii) detecting the peptide via
      electrical nanopore recordings. Our approach is beneficial in several ways.
      First, by eliminating serum components, we overcome limitations of nanopore
      sensing when challenging samples lead to membrane instability and a poor signal
      to-noise ratio. Second, the label-free sensing avoids drawbacks of currently used
      radiolabel-immunoassays for renin. Finally, the strategy of simultaneous
      generation and purification of a signal peptide within a multifunctional resin
      can very likely be expanded to other hydrolytic enzymes dissolved in any analyte
      matrix and exploited for analytical read-out methods other than nanopore sensing.

PMID- 26305575
TI  - Unravelling the Bacterial Vaginosis-Associated Biofilm: A Multiplex Gardnerella
      vaginalis and Atopobium vaginae Fluorescence In Situ Hybridization Assay Using
      Peptide Nucleic Acid Probes.
AB  - Bacterial vaginosis (BV), a condition defined by increased vaginal discharge
      without significant inflammation, is characterized by a change in the bacterial
      composition of the vagina. Lactobacillus spp., associated with a healthy vaginal
      microbiome, are outnumbered by BV-associated organisms. These bacteria could form
      a polymicrobial biofilm which allows them to persist in spite of antibiotic
      treatment. In this study, we examined the presence of Gardnerella vaginalis and
      Atopobium vaginae in vaginal biofilms using Peptide Nucleic Acid (PNA) probes
      targeting these bacteria. For this purpose, we developed three new PNA probes for
      A. vaginae. The most specific A. vaginae probe, AtoITM1, was selected and then
      used in an assay with two existing probes, Gard162 and BacUni-1, to evaluate
      multiplex FISH on clinical samples. Using quantitative polymerase chain reaction
      (qPCR) as the gold standard, we demonstrated a sensitivity of 66.7% (95%
      confidence interval: 54.5% - 77.1%) and a specificity of 89.4% (95% confidence
      interval: 76.1% - 96%) of the new AtoITM1 probe. FISH enabled us to show the
      presence of a polymicrobial biofilm in bacterial vaginosis, in which Atopobium
      vaginae is part of a Gardnerella vaginalis-dominated biofilm. We showed that the
      presence of this biofilm is associated with high bacterial loads of A. vaginae
      and G. vaginalis. 

PMID- 26305577
TI  - Improving Child Oral Health: Cost Analysis of a National Nursery Toothbrushing
      Programme.
AB  - Dental caries is one of the most common diseases of childhood. The aim of this
      study was to compare the cost of providing the Scotland-wide nursery
      toothbrushing programme with associated National Health Service (NHS) cost
      savings from improvements in the dental health of five-year-old children: through
      avoided dental extractions, fillings and potential treatments for decay. METHODS:
      Estimated costs of the nursery toothbrushing programme in 2011/12 were requested
      from all Scottish Health Boards. Unit costs of a filled, extracted and decayed
      primary tooth were calculated using verifiable sources of information. Total
      costs associated with dental treatments were estimated for the period from
      1999/00 to 2009/10. These costs were based on the unit costs above and using the
      data of the National Dental Inspection Programme and then extrapolated to the
      population level. Expected cost savings were calculated for each of the
      subsequent years in comparison with the 2001/02 dental treatment costs.
      Population standardised analysis of hypothetical cohorts of 1000 children per
      deprivation category was performed. RESULTS: The estimated cost of the nursery
      toothbrushing programme in Scotland was L1,762,621 per year. The estimated cost
      of dental treatments in the baseline year 2001/02 was L8,766,297, while in
      2009/10 it was L4,035,200. In 2002/03 the costs of dental treatments increased by
      L213,380 (2.4%). In the following years the costs decreased dramatically with the
      estimated annual savings ranging from L1,217,255 in 2003/04 (13.9% of costs in
      2001/02) to L4,731,097 in 2009/10 (54.0%). Population standardised analysis by
      deprivation groups showed that the largest decrease in modelled costs was for the
      most deprived cohort of children. CONCLUSIONS: The NHS costs associated with the
      dental treatments for five-year-old children decreased over time. In the eighth
      year of the toothbrushing programme the expected savings were more than two and a
      half times the costs of the programme implementation.

PMID- 26305578
TI  - Direct Transformation from Graphitic C3N4 to Nitrogen-Doped Graphene: An
      Efficient Metal-Free Electrocatalyst for Oxygen Reduction Reaction.
AB  - Carbon-based nanomaterials provide an attractive perspective to replace precious
      Pt-based electrocatalysts for oxygen reduction reaction (ORR) to enhance the
      practical applications of fuel cells. Herein, we demonstrate a one-pot direct
      transformation from graphitic-phase C3N4 (g-C3N4) to nitrogen-doped graphene. g
      C3N4, containing only C and N elements, acts as a self-sacrificing template to
      construct the framework of nitrogen-doped graphene. The relative contents of
      graphitic and pyridinic-N can be well-tuned by the controlled annealing process.
      The resulting nitrogen-doped graphene materials show excellent electrocatalytic
      activity toward ORR, and much enhanced durability and tolerance to methanol in
      contrast to the conventional Pt/C electrocatalyst in alkaline medium. It is
      determined that a higher content of N does not necessarily lead to enhanced
      electrocatalytic activity; rather, at a relatively low N content and a high ratio
      of graphitic-N/pyridinic-N, the nitrogen-doped graphene obtained by annealing at
      900  degrees C (NGA900) provides the most promising activity for ORR. This study
      may provide further useful insights on the nature of ORR catalysis of carbon
      based materials. 

PMID- 26305579
TI  - Biological Effect of Ultraviolet Photocatalysis on Nanoscale Titanium with a
      Focus on Physicochemical Mechanism.
AB  - Physicochemical properties, regulated by various surface modifications, influence
      the biological performance of materials. The interaction between surface charge
      and biomolecules is key to understanding the mechanism of surface-tissue
      integration. The objective of this study was to evaluate the biological response
      to a nanoscale titanium surface after ultraviolet (UVC, lambda = 250 +/- 20 nm)
      irradiation and to analyze the effects via a physicochemical mechanism. The
      surface characteristics were evaluated by field-emission scanning electron
      microscopy, X-ray photoelectron spectroscopy, surface profilometry, and contact
      angle assay. In addition, we applied the zeta-potential, a direct method to
      measure the electrostatic charge on UV-treated and UV-untreated titanium nanotube
      surfaces. The effect of the Ti surface after UV treatment on the biological
      process was determined by analyzing bovine serum albumin (BSA) adsorption and
      osteoblast-like MG-63 early adhesion, morphology, cytoskeletal arrangement,
      proliferation, and focal adhesion. Compared to an anodized titanium nanotube
      coating, UV irradiation altered the contact angles on the control surface from
      51.5 degrees  to 6.2 degrees  without changing the surface topography or
      roughness. Furthermore, titanium nanotubes after UV treatment showed a
      significant reduction in the content of acidic hydroxyl groups and held less
      negative charge than the anodized coating. With regard to the biological
      response, along with an enhanced capability to adsorb BSA, osteoblasts exhibited
      higher colonization and viability on the UV-treated material. The results suggest
      that UV treatment enhances the biocompatibility by reducing the electrostatic
      repulsion between biomaterials and biomolecules. 

PMID- 26305581
TI  - Preface to this special issue on chemical biology and drug discovery.

PMID- 26305580
TI  - The expression of gingival epithelial junctions in response to subgingival
      biofilms.
AB  - Periodontitis is an infectious inflammatory disease that destroys the tooth
      supporting tissues. It is caused by the formation of subgingival biofilms on the
      surface of the tooth. Characteristic bacteria associated with subgingival
      biofilms are the Gram-negative anaerobes Porphyromonas gingivalis, Tannerella
      forsythia and Treponema denticola, collectively known as the "red complex"
      species. Inter-epithelial junctions ensure the barrier integrity of the gingival
      epithelium. This may however be disrupted by the biofilm challenge. The aim of
      this in vitro study was to investigate the effect of subgingival biofilms on the
      expression of inter-epithelial junctions by gingival epithelia, and evaluate the
      relative role of the red complex. Multi-layered human gingival epithelial
      cultures were challenged with a 10-species in vitro subgingival biofilm model, or
      its variant without the red complex, for 3 h and 24 h. A low-density array
      microfluidic card platform was then used for analyzing the expression of 62 genes
      encoding for tight junctions, gap junctions, adherens junctions, and desmosomes.
      Although there was a limited effect of the biofilms on the expression of tight,
      adherens and gap junctions, the expression of a number of desmosomal components
      was affected. In particular, Desmoglein-1 displayed a limited and transient up
      regulation in response to the biofilm. In contrast, Desmocollin-2, Desmoplakin
      and Plakoglobin were down-regulated equally by both biofilm variants, after 24 h.
      In conclusion, this subgingival biofilm model may down-regulate selected
      desmosomal junctions in the gingival epithelium, irrespective of the presence of
      the "red complex." In turn, this could compromise the structural integrity of the
      gingival tissue, favoring bacterial invasion and chronic infection.

PMID- 26305582
TI  - General Self-Assembly Route toward Sparsely Studded Noble-Metal Nanocrystals
      inside Graphene Hollow Sphere Network for Ultrastable Electrocatalyst
      Utilization.
AB  - Herein, we rationally design and construct a novel type of sparsely studded noble
      metal nanocrystals inside graphene hollow sphere network (abbreviated as noble
      metal@G HSN) through an electrostatic-attraction-directed self-assembly approach.
      The formation of Pt@G and Pd@G hollow sphere networks have been illustrated as
      examples using SiO2 spheres as templates. Moreover, the electrocatalytic
      performance of the Pt@G HSN for methanol oxidation reaction has been examined as
      a proof-of-concept demonstration of the compositional and structural
      superiorities of noble-metal@G HSN toward electrocatalyst utilization. The as
      prepared Pt@G HSN manifests higher catalytic activity and markedly enhanced long
      term durability in comparison with commercial Pt/C catalyst. 

PMID- 26305584
TI  - A Metal Organic Framework with Spherical Protein Nodes: Rational Chemical Design
      of 3D Protein Crystals.
AB  - We describe here the construction of a three-dimensional, porous, crystalline
      framework formed by spherical protein nodes that assemble into a prescribed
      lattice arrangement through metal-organic linker-directed interactions. The
      octahedral iron storage enzyme, ferritin, was engineered in its C3 symmetric
      pores with tripodal Zn coordination sites. Dynamic light scattering and
      crystallographic studies established that this Zn-ferritin construct could
      robustly self-assemble into the desired bcc-type crystals upon coordination of a
      ditopic linker bearing hydroxamic acid functional groups. This system represents
      the first example of a ternary protein-metal-organic crystalline framework whose
      formation is fully dependent on each of its three components. 

PMID- 26305585
TI  - Developing imidazole analogues as potential inhibitor for Leishmania donovani
      trypanothione reductase: virtual screening, molecular docking, dynamics and ADMET
      approach.
AB  - Visceral leishmaniasis (VL) affects Indian subcontinent, African and South
      American continent, and it covers 70 countries worldwide. Visceral form of
      leishmaniasis is caused by Leishmania donovani in Indian subcontinent which is
      lethal if left untreated. Extensive resistance to antileishmanial drugs such as
      sodium stibogluconate, pentamidine and miltefosine and their decreased efficacy
      has been reported in the endemic region. Amphotericin B drug has shown good
      antileishmanial activity with significant toxicity, but its cost of treatment has
      limited the outreach of this treatment to affected people living in endemic zone.
      So, there is an urgent need to identify new antileishmanial drugs with excellent
      activity and minimal toxicity issues. Trypanothione reductase, a component of
      antioxidant system, is necessary for parasite growth and survival to raise
      infection. To develop potential inhibitor, we docked nine hundred and eighty-four
      5-nitroimidazole analogues along with clomipramine which is a well-known
      inhibitor for TR. Total one hundred and forty-seven 5-nitroimidazole analogues
      with better docking score than clomipramine were chosen for ADMET and QikProp
      studies. Among these imidazole analogues, total twenty-four imidazole analogues
      and clomipramine were chosen on the basis of their ADMET, QikProp, and prime MM
      GBSA study. Later on, two analogues with best MM-GBSA dG bind were undergone
      molecular dynamic simulation to ensure protein-ligand interactions. Using above
      approach, we confirm that ethyl 2-acetyl-5-[4-butyl-2-(3-hydroxypentyl)-5-nitro
      1H-imidazol-1-yl]pent-2-enoate can be a drug candidate against L. donovani for
      the treatment of VL in the Indian subcontinent. 

PMID- 26305586
TI  - Temozolomide Treatment for Pediatric Refractory Anaplastic Ependymoma with Low
      MGMT Protein Expression.
AB  - The benefit of postoperative chemotherapy for anaplastic ependymoma remains
      unknown. We report two pediatric patients with refractory anaplastic ependymoma
      treated with temozolomide (TMZ). We did not detect O(6) -methylguanine-DNA
      methyltransferase (MGMT) promoter methylation in tumor samples; however, MGMT
      protein expression was low. With TMZ treatment, one patient had a 7-month
      complete remission; the other, stable disease for 15 months. Three other patients
      did not respond to TMZ; two had high and one low MGMT expression, and two showed
      no MGMT promoter methylation. These findings suggest that TMZ may be effective
      for pediatric refractory anaplastic ependymoma with low MGMT protein expression.

PMID- 26305587
TI  - Time window for positive cerebrospinal fluid broad-range bacterial PCR and
      Streptococcus pneumoniae immunochromatographic test in acute bacterial
      meningitis.
AB  - BACKGROUND: Reliable microbiological tests are essential for the diagnosis of
      acute bacterial meningitis (ABM). In this study we investigated the time period
      after the start of antibiotic therapy during which culture, polymerase chain
      reaction (PCR) and the immunochromatographic test (ICT) are able to detect
      bacteria in cerebrospinal fluid (CSF). METHODS: The study was performed on CSF
      samples from adults with ABM admitted to the Department of Infectious Diseases,
      Sahlgrenska University Hospital, Gothenburg, Sweden, from January 2007 to April
      2014. In addition to the initial lumbar puncture (LP), the participants underwent
      one or two more LPs during 10 days following the start of antibiotics. The
      analyses performed on the CSF samples were culture, PCR and ICT. RESULTS: The
      study comprised 70 CSF samples from 25 patients with ABM. A bacterium could be
      identified by CSF culture in 44%, by blood culture in 58% and by PCR in 100% of
      the patients. There were no positive CSF cultures in samples taken later than the
      day of starting antibiotics. PCR was positive in 89% on days 1-3, 70% on days 4-6
      and 33% on days 7-10. For cases of pneumococcal meningitis, the ICT was positive
      in 88% on days 1-3, 90% on days 4-6 and 75% on days 7-10. CONCLUSIONS: This study
      shows that PCR is highly sensitive for bacterial detection in CSF samples taken
      up to 1 week into antibiotic therapy. The ICT is highly sensitive for the
      detection of pneumococci in CSF samples taken during the first week of antibiotic
      treatment.

PMID- 26305588
TI  - A Phosphoinositide Code for Primary Cilia.
AB  - How phosphoinositide metabolism is coupled to primary cilia physiology is poorly
      understood. Reporting recently in Developmental Cell, Chavez et al. (2015) and
      Garcia-Gonzalo et al. (2015) show that INPP5E-mediated phosphoinositide
      metabolism, which creates a specific phosphoinositide distribution, ensures
      proper protein trafficking and Hh signaling in primary cilia.

PMID- 26305589
TI  - Don't Go with the Cytoplasmic Flow.
AB  - Cytoplasmic streaming occurs in a variety of organisms, but its biological
      function is often unclear. In this issue of Developmental Cell, Pieuchot et al.
      (2015) report that streaming creates subcellular compartments in the filamentous
      fungus Neurospora crassa. Nuclei immobilized within these compartments
      differentiate and may drive a compartment-specific genetic program.

PMID- 26305590
TI  - Making a Choice: How Cadherin Switching Controls Cell Migration.
AB  - Cells that undergo epithelial-to-mesenchymal transitions (EMTs) commonly switch
      from expressing E-cadherin to N-cadherin. But why this occurs is not well
      understood. In the current issue of Developmental Cell, Scarpa et al. (2015)
      identify a reason: cadherin switching controls Rac signaling to determine how
      cell locomotion is regulated by contact.

PMID- 26305591
TI  - Moving Inward: Establishing the Mammalian Inner Cell Mass.
AB  - Early in mammalian development, a few cells move to the center of the embryo to
      establish the inner cell mass-the early precursor of the fetus. In this issue of
      Developmental Cell, Samarage et al. (2015) shed light on how these cells move
      inward.

PMID- 26305593
TI  - Cellular Subcompartments through Cytoplasmic Streaming.
AB  - Cytoplasmic streaming occurs in diverse cell types, where it generally serves a
      transport function. Here, we examine streaming in multicellular fungal hyphae and
      identify an additional function wherein regimented streaming forms distinct
      cytoplasmic subcompartments. In the hypha, cytoplasm flows directionally from
      cell to cell through septal pores. Using live-cell imaging and computer
      simulations, we identify a flow pattern that produces vortices (eddies) on the
      upstream side of the septum. Nuclei can be immobilized in these microfluidic
      eddies, where they form multinucleate aggregates and accumulate foci of the HDA-2
      histone deacetylase-associated factor, SPA-19. Pores experiencing flow degenerate
      in the absence of SPA-19, suggesting that eddy-trapped nuclei function to
      reinforce the septum. Together, our data show that eddies comprise a subcellular
      niche favoring nuclear differentiation and that subcompartments can be self
      organized as a consequence of regimented cytoplasmic streaming. 

PMID- 26305592
TI  - Phosphoinositides Regulate Ciliary Protein Trafficking to Modulate Hedgehog
      Signaling.
AB  - Primary cilia interpret vertebrate Hedgehog (Hh) signals. Why cilia are essential
      for signaling is unclear. One possibility is that some forms of signaling require
      a distinct membrane lipid composition, found at cilia. We found that the ciliary
      membrane contains a particular phosphoinositide, PI(4)P, whereas a different
      phosphoinositide, PI(4,5)P2, is restricted to the membrane of the ciliary base.
      This distribution is created by Inpp5e, a ciliary phosphoinositide 5-phosphatase.
      Without Inpp5e, ciliary PI(4,5)P2 levels are elevated and Hh signaling is
      disrupted. Inpp5e limits the ciliary levels of inhibitors of Hh signaling,
      including Gpr161 and the PI(4,5)P2-binding protein Tulp3. Increasing ciliary
      PI(4,5)P2 levels or conferring the ability to bind PI(4)P on Tulp3 increases the
      ciliary localization of Tulp3. Lowering Tulp3 in cells lacking Inpp5e reduces
      ciliary Gpr161 levels and restores Hh signaling. Therefore, Inpp5e regulates
      ciliary membrane phosphoinositide composition, and Tulp3 reads out ciliary
      phosphoinositides to control ciliary protein localization, enabling Hh signaling.

PMID- 26305594
TI  - Myostatin: expanding horizons.
AB  - Myostatin is a secreted growth and differentiation factor that belongs to the TGF
      beta superfamily. Myostatin is predominantly synthesized and expressed in
      skeletal muscle and thus exerts a huge impact on muscle growth and function. In
      keeping with its negative role in myogenesis, myostatin expression is tightly
      regulated at several levels including epigenetic, transcriptional, post
      transcriptional, and post-translational. New revelations regarding myostatin
      regulation also offer mechanisms that could be exploited for developing myostatin
      antagonists. Increasingly, it is becoming clearer that besides its conventional
      role in muscle, myostatin plays a critical role in metabolism. Hence, molecular
      mechanisms by which myostatin regulates several key metabolic processes need to
      be further explored.

PMID- 26305596
TI  - Body composition and resting metabolic rate of perimenopausal women using
      continuous progestogen contraception.
AB  - OBJECTIVE: The effect on body composition and in particular on fat mass (FM) of
      12 months' use of a desogestrel (DSG)-only contraceptive pill or the
      levonorgestrel-releasing intrauterine system (LNG-IUS) was evaluated in women in
      the perimenopause. METHODS: An observational study comprised 102 perimenopausal
      women: 42 received a 75 MUg DSG pill, 34 received the 52 mg LNG-IUS, and 26
      received no treatment. Body composition, body weight and resting metabolic rate
      (RMR) were evaluated at baseline and again after 12 months. RESULTS: FM did not
      change in the control group (- 0.5 +/- 1.6%) but significantly increased in the
      LNG-IUS group (+ 1.1 +/- 2.9%; p = 0.02 vs. controls) and in the DSG group (+ 2.8
      +/- 3.5%; p = 0.0001 vs. controls; p = 0.02 vs. LNG-IUS). Women treated with DSG
      or the LNG-IUS showed a non-significant increase in body weight, body mass index
      and waist circumference. RMR did not significantly vary in the control group (-
      3.8 +/- 292.9 kJ/ 24 h) and tended to decrease but not significantly in the LNG
      IUS (115.5 +/- 531.8 kJ/ 24 h) and DSG groups (305.9 +/- 556.9 kJ/24 h).
      CONCLUSIONS: The results of this preliminary study seem to indicate that in
      perimenopausal women continuous use of the DSG-only pill and to a lesser extent
      the LNG-IUS may favour FM accumulation.

PMID- 26305597
TI  - Biological Activity of Mesoporous Dendrimer-Coated Titanium Dioxide: Insight on
      the Role of the Surface-Interface Composition and the Framework Crystallinity.
AB  - Hitherto, the field of nanomedicine has been overwhelmingly dominated by the use
      of mesoporous organosilicas compared to their metal oxide congeners. Despite
      their remarkable reactivity, titanium oxide-based materials have been seldom
      evaluated and little knowledge has been gained with respect to their "structure
      biological activity" relationship. Herein, a fruitful association of phosphorus
      dendrimers (both "ammonium-terminated" and "phosphonate-terminated") and titanium
      dioxide has been performed by means of the sol-gel process, resulting in
      mesoporous dendrimer-coated nanosized crystalline titanium dioxide. A similar
      organo-coating has been reproduced using single branch-mimicking dendrimers that
      allow isolation of an amorphous titanium dioxide. The impact of these materials
      on red blood cells was evaluated by studying cell hemolysis. Next, their
      cytotoxicity toward B14 Chinese fibroblasts and their antimicrobial activity were
      also investigated. Based on their variants (cationic versus anionic terminal
      groups and amorphous versus crystalline titanium dioxide phase), better
      understanding of the role of the surface-interface composition and the nature of
      the framework has been gained. No noticeable discrimination was observed for
      amorphous and crystalline material. In contrast, hemolysis and cytotoxicity were
      found to be sensitive to the nature of the interface composition, with the
      ammonium-terminated dendrimer-coated titanium dioxide being the most hemolytic
      and cytotoxic material. This surface-functionalization opens the door for
      creating a new synergistic machineries mechanism at the cellular level and seems
      promising for tailoring the biological activity of nanosized organic-inorganic
      hybrid materials. 

PMID- 26305598
TI  - Engineering Synthetic cis-Regulatory Elements for Simultaneous Recognition of
      Three Transcriptional Factors in Bacteria.
AB  - Recognition of cis-regulatory elements by transcription factors (TF) at target
      promoters is crucial to gene regulation in bacteria. In this process, binding of
      TFs to their cognate sequences depends on a set of physical interactions between
      these proteins and specific nucleotides in the operator region. Previously, we
      showed that in silico optimization algorithms are able to generate short
      sequences that are recognized by two different TFs of Escherichia coli, namely,
      CRP and IHF, thus generating an AND logic gate. Here, we expanded this approach
      in order to engineer DNA sequences that can be simultaneously recognized by three
      unrelated TFs (CRP, IHF, and Fis). Using in silico optimization and experimental
      validation strategies, we were able to obtain a candidate promoter (Plac-CFI1)
      regulated by only two TFs with an AND logic, thus demonstrating a limitation in
      the design. Subsequently, we modified the algorithm to allow the optimization of
      extended sequences, and were able to design two synthetic promoters (PCFI20-1 and
      PCFI22-5) that were functional in vivo. Expression assays in E. coli mutant
      strains for each TF revealed that while CRP positively regulates the promoter
      activities, IHF and Fis are strong repressors of both the promoter variants.
      Taken together, our results demonstrate the potential of in silico strategies in
      bacterial synthetic promoter engineering. Furthermore, the study also shows how
      small modifications in cis-regulatory elements can drastically affect the final
      logic of the resulting promoter. 

PMID- 26305599
TI  - Theoretical Study of Renewable Ionic Liquids in the Pure State and with Graphene
      and Carbon Nanotubes.
AB  - The N-ethyl-N-(furan-2-ylmethyl)ethanaminium dihydrogen phosphate ionic liquid
      was studied as a model of ionic liquids which can be produced from totally
      renewable sources. A computational study using both molecular dynamics and
      density functional theory methods was carried out. The properties, structuring,
      and intermolecular interactions (hydrogen bonding) of this fluid in the pure
      state were studied as a function of pressure and temperature. Likewise, the
      adsorption on graphene and the confinement between graphene sheets was also
      studied. The solvation of single walled carbon nanotubes in the selected ionic
      liquid was analyzed together with the behavior of ions confined inside these
      nanotubes. The reported results show remarkable properties for this fluid, which
      show that many of the most relevant properties of ionic liquids and their ability
      to interact with carbon nanosystems may be maintained and even improved using new
      families of renewable compounds instead of classic types of ionic liquids with
      worse environmental, toxicological, and economical profiles. 

PMID- 26305600
TI  - Lanthanide(III) and lead(II) complexes of a chiral nonaaza macrocyclic amine
      based on 1,2-diaminocyclopentane.
AB  - The macrocyclic nonaaza 3 + 3 amine based on diaminocyclopentane forms
      enantiopure helical complexes with lanthanide(III) ions. In contrast to analogous
      complexes based on 1,2-trans-diaminocyclohexane, no clear helicity process is
      observed. Crystal structures of these compounds show tight helical wrapping of
      the macrocycle around the lanthanide(III) ion leading to the formation of a
      double helix. In contrast, more "open" conformation is observed for the free
      macrocycle. Similar double-helical conformation of the ligand was also observed
      for the lead(II) complex. In the case of this complex the NMR spectra indicate a
      dynamic process in which the C2-symmetric molecule observed in the solid state
      gives rise to an effective, averaged D3-symmetry in solution at elevated
      temperatures.

PMID- 26305602
TI  - Overexpression of Fli-1 is associated with adverse prognosis of endometrial
      cancer.
AB  - This study aimed to investigate the expression of Friend leukemia virus
      integration 1 (Fli-1) and its correlation with the prognosis of endometrial
      cancer (EC). Thirty-two EC tissue samples were evaluated for Fli-1 expression
      using immunohistochemistry. Fli-1 showed significantly high expression in EC
      cells, followed by hyperplasia cells, and was negative in adjacent normal
      tissues. The high expression of Fli-1 was significantly associated with a high
      differentiation grade, mutated P53 expression, and histological subtype (p <
      .05). Downregulation of Fli-1 in AN3CN cells using RNA interference inhibited
      cell clone formation and proliferation but did not affect apoptosis and migration
      of the cells. This study provides the first evidence that Fli-1 expression
      gradually increases in parallel with disease progression, and its overexpression
      might predict poor prognosis in EC. 

PMID- 26305601
TI  - Carbonic anhydrase IX induction defines a heterogeneous cancer cell response to
      hypoxia and mediates stem cell-like properties and sensitivity to HDAC
      inhibition.
AB  - Carbonic anhydrase IX (CAIX) is strongly induced by hypoxia and its
      overexpression is associated with poor therapeutic outcome in cancer. Here, we
      report that hypoxia promotes tumour heterogeneity through the epigenetic
      regulation of CAIX. Based on hypoxic CAIX expression we identify and characterize
      two distinct populations of tumour cells, one that has inducible expression of
      CAIX and one that does not. The CAIX+ve population is enriched with cells
      expressing cancer stem cell markers and which have high self-renewal capacity. We
      show that differential CAIX expression is due to differences in chromatin
      structure. To further investigate the relationship between chromatin organization
      and hypoxic induction of CAIX expression we investigated the effect of JQ1 an
      inhibitor of BET bromodomain proteins and A366 a selective inhibitor of the H3K9
      methyltransferase G9a/GLP. We identified that these drugs were able to modulate
      hypoxic CAIX expression induction. This further highlights the role of epigenetic
      modification in adaption to hypoxia and also in regulation of heterogeneity of
      cells within tumours. Interestingly, we identified that the two subpopulations
      show a differential sensitivity to HDAC inhibitors, NaBu or SAHA, with the CAIX
      positive showing greater sensitivity to treatment. We propose that drugs
      modulating chromatin regulation of expression may be used to reduce heterogeneity
      induced by hypoxia and could in combination have significant clinical
      consequences. 

PMID- 26305603
TI  - Using mHealth to Deliver Behavior Change Interventions Within Prenatal Care at
      Community Health Centers.
AB  - PURPOSE: To test an iPad-delivered multiple behavior tailored intervention
      (Healthy Pregnancy: Step by Step) for pregnant women that addresses smoking
      cessation, stress management, and fruit and vegetable consumption. DESIGN: A
      randomized 2 * 5 factorial repeated measures design was employed with
      randomization on the individual level stratified on behavior risk. Women
      completed three sessions during pregnancy and two postpartum at postdelivery
      months 1 and 4. SETTING: Women were recruited from six locations of federally
      funded health centers across three states. SUBJECTS: Participants (N = 335) were
      English- and Spanish-speaking women at up to 18 weeks gestation. INTERVENTION:
      The treatment group received three interactive sessions focused on two priority
      health behavior risks. The sessions offered individually tailored and stage
      matched change strategies based on the transtheoretical model of behavior change.
      The usual care group received March of Dimes brochures. MEASURES: The primary
      outcome was the number of behavior risks. Stage of change and continuous measures
      for all behaviors also were assessed. ANALYSIS: Data were analyzed across all
      time points using generalized estimating equations examining repeated measures
      effects. RESULTS: Women in the treatment group reported significantly fewer risks
      than those in usual care at 1 month (.85 vs. 1.20, odds ratio [OR] = .70) and 4
      months postpartum (.72 vs. .91, OR = .81). CONCLUSION: Healthy Pregnancy is an
      evidence-based and personalized program that assists pregnant women with reducing
      behavior risks and sustaining healthy lifestyle behaviors.

PMID- 26305604
TI  - Healthful Nutrition of Foods in Navajo Nation Stores: Availability and Pricing.
AB  - PURPOSE: Low availability and affordability of healthier foods in food stores on
      the Navajo Nation (NN) may be a community-level risk factor for the high
      prevalence of obesity among the Navajo people. This study assessed the
      availability and pricing of foods and beverages in supermarkets and convenience
      stores throughout the NN. DESIGN: Descriptive study design using the Nutrition
      Environment Measurement Survey in Stores audit tool. SETTING: Supermarkets (n =
      13) and convenience stores (n = 50) on NN and border-town supermarkets (n = 9).
      SUBJECTS: Not applicable. MEASURES: Availability and pricing of healthy and less
      healthy foods. ANALYSIS: Descriptive and chi(2) analyses. RESULTS: Navajo
      convenience stores offered fewer healthier food options compared to Navajo
      supermarkets. In Navajo convenience stores, 100% whole grain products, reduced
      fat cheese, lean meats, reduced-fat chips, and fat-free or light hot dogs were
      available in fewer stores than their corresponding less-healthy versions (all
      with p < .05). In both Navajo supermarkets and convenience stores, 100% whole
      wheat bread, lean cold cuts, and reduced-fat cheese were all more expensive per
      unit than their corresponding less-healthy versions (all with p < .05).
      CONCLUSIONS: According to this study, healthier foods are not as readily
      available in Navajo convenience stores as they are in Navajo supermarkets.
      Improving access to and affordability of healthier foods in reservation stores of
      all sizes may support healthy eating among Navajo residents.

PMID- 26305606
TI  - Promoting Influenza Vaccination to Restaurant Employees.
AB  - PURPOSE: To evaluate an evidence-based workplace approach to increasing adult
      influenza vaccination levels applied in the restaurant setting DESIGN: We
      implemented an intervention and conducted a pre/post analysis to determine effect
      on vaccination. SETTING: Eleven Seattle-area restaurants. SUBJECTS: Restaurants
      with 25+ employees speaking English or Spanish and over 18 years. INTERVENTION:
      Restaurants received influenza vaccination promotion materials, assistance
      arranging on-site vaccination events, and free influenza vaccinations for
      employees. MEASURES: Pre/post employee surveys of vaccination status with direct
      observation and employer interviews to evaluate implementation. ANALYSIS: We
      conducted descriptive analysis of employee survey data and performed qualitative
      analysis of implementation data. To assess intervention effect, we used a mixed
      effects logistic regression model with a restaurant-specific random effect.
      RESULTS: Vaccination levels increased from 26% to 46% (adjusted odds ratio 2.33,
      95% confidence interval 1.69, 3.22), with 428 employees surveyed preintervention,
      305 surveyed postintervention, and response rates of 73% and 55%, respectively.
      The intervention was effective across subgroups, but there were restaurant-level
      differences. CONCLUSION: An access-based workplace intervention can increase
      influenza vaccination levels in restaurant employees, but restaurant-level
      factors may influence success.

PMID- 26305607
TI  - A Reach, Effectiveness, Adoption, Implementation, Maintenance Evaluation of
      Weekend Backpack Food Assistance Programs.
AB  - PURPOSE: The purpose of this study was to evaluate an ongoing statewide weekend
      backpack program through the Reach, Effectiveness, Adoption, Implementation, and
      Maintenance (RE-AIM) framework. DESIGN: Mixed-methods inquiry was used to explore
      the reach, effectiveness, adoption, implementation, and maintenance of backpack
      programs within Montana. SETTING: Study participants completed audio-recorded one
      on-one phone interviews. PARTICIPANTS: Key informants (e.g., managers at food
      banks, staff at participating schools, policy makers) were purposively sampled (N
      = 20). METHOD: Semistructured interviews were conducted to gather data to
      describe each RE-AIM dimension. Interviews were transcribed verbatim and
      deductively (i.e., using RE-AIM as themes) coded for meaning units, placed into
      higher-order categories, and summarized in narrative. Supporting quantitative
      data (e.g., the proportion of eligible students that joined the program, rate of
      school-level adoption) were calculated using descriptive statistics. RESULTS:
      Backpack programs with a broad reach and evidenced effect may be appealing to
      adopt. Weekend food bags cost an average $3.87 (SD +/- .94) and there were some
      positive (i.e., ease, protecting participants' privacy) and very few negative
      (logistical) components of implementation. Collaborators and community partners
      are necessary for long-term sustainability. CONCLUSION: Backpack programs are
      widespread and have potential to relieve weekend hunger; however, more efforts
      need to be made to end childhood hunger.

PMID- 26305608
TI  - Neighborhood Attributes Associated With the Social Environment.
AB  - PURPOSE: To examine the association between specific attributes of neighborhood
      environments and four social environment measures. DESIGN: Data were collected as
      part of a baseline survey among participants enrolling in a walking intervention.
      SETTING: Participants were recruited from a metropolitan area in a Southeastern
      state. SUBJECTS: Participants (n = 294) were predominantly African-American (67%)
      and female (86%), with some college education (79%) and a mean age of 49.
      MEASURES: The International Physical Activity Questionnaire Environment Module
      assessed perceptions about neighborhood attributes. The social environment was
      assessed using three distinct scales: social cohesion, social interactions with
      neighbors, and social support for physical activity from family and friends.
      ANALYSIS: Multiple regression models examined associations between neighborhood
      attributes and social environment measures, adjusting for demographic variables.
      RESULTS: Having walkable destinations and having access to amenities and transit
      stops were associated with increased interactions with neighbors (b = 1.32, 1.04,
      and 1.68, respectively, p < .05). Attributes related to structural support for
      physical activity (sidewalks, street connectivity, recreation facilities) were
      associated with increased interactions with neighbors (b = 1.47, 1.34, and 1.13,
      respectively, p < .05). Bicycling facilities that were maintained (i.e., bike
      lanes, racks) were associated with social support for physical activity from
      family and friends (b = .43 and .30, respectively, p < .05). CONCLUSION: The
      study highlights key attributes of neighborhood environments that may be
      associated with the social context of such settings.

PMID- 26305609
TI  - Improvements in Health Behaviors, Eating Self-Efficacy, and Goal-Setting Skills
      Following Participation in Wellness Coaching.
AB  - Purpose . This project examined potential changes in health behaviors following
      wellness coaching. Design . In a single cohort study design, wellness coaching
      participants were recruited in 2011, data were collected through July 2012, and
      were analyzed through December 2013. Items in the study questionnaire used
      requested information about 11 health behaviors, self-efficacy for eating, and
      goal-setting skills. Setting . Worksite wellness center. Participants . One
      hundred employee wellness center members with an average age of 42 years; 90%
      were female and most were overweight or obese. Intervention . Twelve weeks of in
      person, one-on-one wellness coaching. Method . Participants completed study
      questionnaires when they started wellness coaching (baseline), after 12 weeks of
      wellness coaching, and at a 3-month follow-up. Results . From baseline to week
      12, these 100 wellness coaching participants improved their self-reported health
      behaviors (11 domains, 0- to 10-point scale) from an average of 6.4 to 7.7 (p <
      .001), eating self-efficacy from an average of 112 to 142 (on a 0- to 180-point
      scale; p < .001), and goal-setting skills from an average of 49 to 55 (on a 16-
      to 80-point scale; p < .001). Conclusion . These results suggest that
      participants improved their current health behaviors and learned skills for
      continued healthy living. Future studies that use randomized controlled trials
      are needed to establish causality for wellness coaching.

PMID- 26305611
TI  - A Multicomponent Intervention Helped Reduce Sugar-Sweetened Beverage Intake in
      Economically Disadvantaged Hispanic Children.
AB  - PURPOSE: This study aimed to examine the effect of a multicomponent intervention
      program on consumption of sugar-sweetened beverages (SSBs), and lifestyle factors
      associated with SSB intake, in Hispanic children from low-income families.
      DESIGN: A five-wave longitudinal study using a quasi-experimental design was
      conducted. SETTING: Five elementary schools in West Texas served as the setting.
      SUBJECTS: Participants included 555 predominantly Hispanic children (ages 5-9
      years) from low-income families and their parents (n = 525). INTERVENTION: A
      multicomponent intervention program was implemented. MEASURES: Children's
      anthropometric measures were obtained. Their weight status was determined based
      on body mass index for age and gender. Parents responded to a demographic
      questionnaire, a shelf inventory, an acculturation scale, and a family survey.
      ANALYSIS: Growth curve analyses were used to test differences between
      intervention and comparison participants' SSB intake and to examine potential
      covariates. RESULTS: Comparison group children's daily SSB intake significantly
      increased over time (B = 1.06 +/- .40 ounces per month, p < .01), but this linear
      increase of SSB was slowed down by the intervention (B = -.29 +/- .12, p < .05).
      More daily TV time, more fast food intake, and more types of SSBs available at
      home were associated with higher SSB intake. CONCLUSION: Risk factors of
      childhood obesity were associated with each other. The intervention program
      produced a modest reduction in SSB consumed by economically disadvantaged and
      predominantly Hispanic children.

PMID- 26305612
TI  - Adolescent and Young Adult Smokers Who Self-Identify as Nonsmokers: Relationship
      With Cigarette-Related Withdrawal and Cravings.
AB  - PURPOSE: Examine the extent to which low-nicotine dependent daily smokers
      identify themselves as nonsmokers (smoking nonsmokers) over time, and examine the
      effect of nicotine-related withdrawal symptoms and cravings in predicting self
      identified smoking status. DESIGN: Longitudinal. SETTING: National Youth Smoking
      Cessation Survey 2003-2005. SUBJECTS: One hundred thirty-two adolescents and
      young adults (16-24 years). MEASURES: A questionnaire was used to assess smoking
      identity, withdrawal, cravings, and smoking intensity parameters. ANALYSIS:
      Multivariable logistic regression analysis. RESULTS: Among the 132 smoking
      nonsmokers at baseline, 45% remained smoking nonsmokers at the 2-year follow-up,
      with 55% transitioning to smoking (i.e., self-identified as smoking smokers in
      the interim). After adjustments, participants exhibiting greater restlessness and
      cravings over time, respectively, had 3.59 (p = .01) and 4.31 (p = .008) greater
      odds of being a smoking nonsmoker at baseline but then transitioning into a
      smoking smoker at 2-year follow-up. CONCLUSION: These findings may have
      implications with respect to interventions emphasizing withdrawal and craving
      symptoms. Further, given that some youth smokers self-identify as nonsmokers, and
      do so over time, potential intervention efforts may be pointed toward cognitive
      related strategies at improving self-perceptions.

PMID- 26305613
TI  - The Effects of Tai Chi on Cardiovascular Risk in Women.
AB  - PURPOSE: This study examined the effects of tai chi (TC) on biobehavioral factors
      associated with cardiovascular disease (CVD) risk in women. DESIGN: A randomized
      trial used a wait-list control group, pretest-posttest design. Data were
      collected immediately before, immediately after, and 2 months following the
      intervention. SETTING: The study was community based in central Virginia.
      SUBJECTS: Women aged 35 to 50 years at increased risk for CVD. INTERVENTION: The
      8-week intervention built on prior work and was designed to impact biobehavioral
      factors associated with CVD risk in women. MEASURES: Biological measures included
      fasting glucose, insulin, and lipids as well as C-reactive protein and cytokines.
      Behavioral measures included fatigue, perceived stress, depressive symptoms,
      social support, mindfulness, self-compassion, and spiritual thoughts and
      behaviors. ANALYSIS: A mixed effects linear model was used to test for
      differences between groups across time. RESULTS: In 63 women, TC was shown to
      decrease fatigue (? [difference in group means] = 9.38, p = .001) and granulocyte
      colony stimulating factor (? = 12.61, p = .052). Consistent with the study model
      and intervention design, significant changes observed 2 months post intervention
      indicated that TC may help down-regulate proinflammatory cytokines associated
      with underlying CVD risk, including interferon gamma (? = 149.90, p = .002),
      tumor necrosis factor (? = 16.78, p = .002), interleukin (IL) 8 (? = 6.47, p =
      .026), and IL-4 (? = 2.13, p = .001), and may increase mindfulness (? = .54, p =
      .021), spiritual thoughts and behaviors (? = 8.30, p = .009), and self-compassion
      (? = .44, p = .045). CONCLUSION: This study contributes important insights into
      the potential benefits and mechanisms of TC and, with further research, may
      ultimately lead to effective strategies for reducing CVD risk in women earlier in
      the CVD trajectory.

PMID- 26305614
TI  - Early Childhood Disadvantage for Sons of Mexican Immigrants: Body Mass Index
      Across Ages 2-5.
AB  - PURPOSE: To distinguish the origins of higher weight status and determine when
      and why intra- and interracial/ethnic disparities emerge. DESIGN: The study used
      a longitudinal analysis of the Early Childhood Longitudinal Study-Birth Cohort
      (ECLS-B). SETTING: The study was conducted in the United States. SUBJECTS:
      Participants were children of non-Hispanic white mothers and children of U.S.-
      and foreign-born mothers of Mexican origin from a nationally representative
      sample of children born in the year 2001 (N ~ 3700). MEASURES: The Centers for
      Disease Control and Prevention growth charts determined sex- and age-specific
      weight status. Covariates were obtained from birth certificate records and parent
      interviews. ANALYSIS: Frequencies, growth curve trajectories, and ordinary least
      squares regression examined body mass index (BMI) and obesity across survey
      waves. RESULTS: Compared to their peers with non-Hispanic white mothers, children
      of Mexican-heritage mothers have higher average BMI and greater rates of obesity.
      The BMI of boys with Mexican-born mothers is higher relative to whites and
      children of U.S.-born Mexican mothers across early childhood, increasing sharply
      at about age 4.5 years. This divergence is driven by increases in the BMI of
      boys, as girls do not show the same growth. A number of measures, including
      descriptors of children's nutritional intake, lifestyle factors, and
      acculturation, do not explain the increased obesity rates among sons of Mexican
      mothers. CONCLUSION: Despite favorable perinatal health and weight, Mexican
      American sons of foreign-born mothers show disadvantages in BMI that emerge close
      to the start of kindergarten.

PMID- 26305616
TI  - Molecular determinants of blood-brain barrier permeation.
AB  - The blood-brain barrier (BBB) is a microvascular unit which selectively regulates
      the permeability of drugs to the brain. With the rise in CNS drug targets and
      diseases, there is a need to be able to accurately predict a priori which
      compounds in a company database should be pursued for favorable properties. In
      this review, we will explore the different computational tools available today,
      as well as underpin these to the experimental methods used to determine BBB
      permeability. These include in vitro models and the in vivo models that yield the
      dataset we use to generate predictive models. Understanding of how these models
      were experimentally derived determines our accurate and predicted use for
      determining a balance between activity and BBB distribution. 

PMID- 26305618
TI  - Subclinical Hypothyroidism and Cognitive Impairment: Systematic Review and Meta
      Analysis.
AB  - BACKGROUND: The association between subclinical hypothyroidism (sHT) and
      cognitive impairment or risk of dementia is not well-defined, especially in the
      elderly, where the assessment of central nervous system function is challenging.
      The aim of this systematic review and meta-analysis was to evaluate the possible
      effect of sHT on cognitive decline and the risk of dementia. METHODS: Cognitive
      function was the primary outcome, evaluated as composite endpoint of incidence or
      prevalence of dementia or difference of Mini Mental State Examination, Wechsler
      Adult Intelligence Scale, and Wechsler Memory Scale-Revised scores. RESULTS:
      Thirteen studies were included in the meta-analysis. A significant risk of
      cognitive alteration was observed only in sHT individuals younger than age 75
      years: composite endpoint odds ratio (OR) 1.56 (95% confidence interval [CI] 1.07
      2.27, P = .02, I(2) = 82.5%), risk of dementia OR 1.81 (95% CI 1.43-2.28, P <
      .01, I(2) = 35%). Mean serum thyroid-stimulating hormone (TSH) levels and the OR
      of composite endpoint were positively correlated. No significant effect of sHT
      was found when considering all the studies as a whole: composite endpoint OR 1.26
      (95% CI 0.96-1.66, P = .09, I(2) = 87.2%), risk of dementia OR 1.42 (95% CI, 0.97
      2.07, P = .07, I(2) = 66.8%), Mini Mental State Examination mean difference 
      0.059 (95% CI -0.464 to 0.346 P = .78, I(2) = 51.8%). CONCLUSIONS: This meta
      analysis demonstrates a relationship between sHT and cognitive impairment only in
      individuals younger than 75 years of age and those with higher TSH
      concentrations. No correlation was found while considering all the studies as a
      whole. The lack of utilization of age-related serum TSH reference ranges and
      consequent potential misdiagnosis of sHT in older people may account for this.

PMID- 26305617
TI  - Effects of TZD Use and Discontinuation on Fracture Rates in ACCORD Bone Study.
AB  - CONTEXT: In trials, thiazolidinediones (TZDs) increase fracture risk in women,
      but the effects of discontinuation are unknown. OBJECTIVE: The objective was to
      investigate the effects of TZD use and discontinuation on fractures in women and
      men. DESIGN: This was a longitudinal observational cohort study using data from
      the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial bone
      ancillary study. Duration of TZD use and discontinuation during ACCORD, assessed
      every 2-4 months at clinic visits, were modeled as time-varying covariates in
      proportional hazards models for occurrence of first non-spine fracture.
      PARTICIPANTS: We studied a total of 6865 participants in ACCORD BONE. MAIN
      OUTCOME MEASURES: Main outcome measures were centrally adjudicated non-spine
      fracture. RESULTS: Average age was 62.4 (SD, 6.6) years; average duration of
      diabetes was 11.1 (SD, 7.8) years. Rosiglitazone was used by 74% and pioglitazone
      by 13% of participants. During a mean follow-up of 4.8 (SD, 1.5) years, 262 men
      and 287 women experienced at least one non-spine fracture. The fracture rate was
      higher in women with 1-2 years of TZD use (hazard ratio [HR] = 2.32; 95%
      confidence interval [CI], 1.49, 3.62) or >2 years of TZD use (HR = 2.01; 95% CI,
      1.35, 2.98), compared with no use. The fracture rate was reduced in women who had
      discontinued TZD use for 1-2 years (HR = 0.57; 95% CI, 0.35, 0.92) or > 2 years
      (HR = 0.42; 95% CI, 0.24, 0.74) compared with current users. TZD use and
      discontinuation were not associated with non-spine fractures in men. CONCLUSIONS:
      TZD use was associated with increased non-spine fractures in women, but not men,
      with type 2 diabetes. When women discontinued TZD use, the fracture effects were
      attenuated.

PMID- 26305619
TI  - Activin A Increases Human Trophoblast Invasion by Inducing SNAIL-Mediated MMP2 Up
      Regulation Through ALK4.
AB  - CONTEXT: Activin A increases matrix metalloproteinase (MMP) 2 expression and cell
      invasion in human trophoblasts, but whether the expression of MMP2 is essential
      for the proinvasive effect of activin A has yet to be determined. Moreover, the
      identity of the activin receptor-like kinase (ALK; TGF-beta type I receptors) and
      downstream transcription factors (eg, SNAIL and SLUG) mediating the effects of
      activin on MMP2 expression and trophoblast cell invasion remains unknown.
      OBJECTIVE: To elucidate the role of MMP2 in activin A-induced human trophoblast
      cell invasion as well as the involvement of ALK4 and SNAIL. DESIGN: HTR8/SVneo
      immortalized human extravillous cytotrophoblast (EVT) cells and primary cultures
      of human first-trimester EVT cells were used as study models. Small interfering
      RNA (siRNA)-mediated knockdown approaches were used to investigate the molecular
      determinants of activin A-mediated functions. MAIN OUTCOME MEASURES: Levels of
      mRNA and protein were examined by reverse transcription-quantitative real-time
      PCR and Western blot, respectively. Cell invasiveness was measured by Matrigel
      coated transwell assays. RESULTS: Treatment of HTR8/SVneo cells with activin A
      increased the production of SNAIL, SLUG, and MMP2 without altering that of MMP9,
      TIMP1, TIMP2, TWIST, RUNX2, ZEB1, or ZEB2. Similarly, activin A up-regulated the
      mRNA and protein levels of SNAIL and MMP2 in primary EVT cells. Knockdown of
      SNAIL attenuated activin A-induced MMP2 up-regulation in HTR8/SVneo and primary
      EVT cells. In HTR8/SVneo cells, activin A-induced production of SNAIL and MMP2
      was abolished by pretreatment with the TGF-beta type I receptor (ALK4/5/7)
      inhibitor SB431542 or siRNA targeting ALK4, SMAD2/3, or common SMAD4. Likewise,
      knockdown of ALK4 or SMAD4 abolished the stimulatory effects of activin A on
      SNAIL and MMP2 expression in primary EVT cells. Importantly, activin A-induced
      HTR8/SVneo and primary EVT cell invasion were attenuated by siRNA-mediated
      depletion of ALK4 or MMP2. CONCLUSION: Activin A induces human trophoblast cell
      invasion by inducing SNAIL-mediated MMP2 expression through ALK4 in a SMAD2/3
      SMAD4-dependent manner.

PMID- 26305620
TI  - Low Population Selenium Status Is Associated With Increased Prevalence of Thyroid
      Disease.
AB  - CONTEXT: Epidemiological studies have supported the premise that an adequate
      selenium intake is essential for thyroid gland function. OBJECTIVE: The objective
      was to investigate whether the prevalence of thyroid disease differed in two
      areas that were similar, except for very different soil/crop selenium
      concentrations. DESIGN: Cross-sectional observational study. SETTING: The setting
      was two counties of Shaanxi Province, China, here defined as adequate- and low
      selenium. PARTICIPANTS: A total of 6152 participants were selected by stratified
      cluster-sampling. MAIN OUTCOME MEASURES: Participants completed demographic and
      dietary questionnaires and underwent physical and thyroid ultrasound
      examinations. Serum samples were analyzed for thyroid function parameters and
      selenium concentration. Serum selenium was compared between different
      demographic, dietary, and lifestyle categories in the two counties. The
      relationship between selenium status, dietary factors, and pathological thyroid
      conditions was explored by logistic regression. RESULTS: Complete data sets were
      available from 3038 adequate-selenium participants and 3114 low-selenium
      participants in whom median (interquartile range) selenium concentrations
      differed almost 2-fold (103.6 [79.7, 135.9] vs 57.4 [39.4, 82.1] MUg/L; P =
      .001). The prevalence of pathological thyroid conditions (hypothyroidism,
      subclinical hypothyroidism, autoimmune thyroiditis, and enlarged thyroid) was
      significantly lower in the adequate-selenium county than in the low-selenium
      county (18.0 vs 30.5%; P < .001). Higher serum selenium was associated with lower
      odds ratio (95% confidence interval) of autoimmune thyroiditis (0.47; 0.35,
      0.65), subclinical hypothyroidism (0.68; 0.58, 0.93), hypothyroidism (0.75; 0.63,
      0.90), and enlarged thyroid (0.75; 0.59, 0.97). CONCLUSIONS: Low selenium status
      is associated with increased risk of thyroid disease. Increased selenium intake
      may reduce the risk in areas of low selenium intake that exist not only in China
      but also in many other parts of the world.

PMID- 26305621
TI  - A Case for Conservative Management: Characterizing the Natural History of
      Radiographically Diagnosed Rathke Cleft Cysts.
AB  - CONTEXT: Rathke cleft cysts (RCCs) are benign embryonic remnants of the Rathke's
      pouch found in 13% to 33% of the general population. When symptomatic, they
      manifest themselves by compressing adjacent structures, causing pressure effects
      such as headache, visual disturbance, or pituitary hormone deficits. Most RCCs
      are asymptomatic, and their management remains controversial. Surgical resection
      has generally been indicated to treat symptomatic RCCs but carries the risk of
      complications. OBJECTIVE: Our objective was to better characterize the outcomes
      for patients with presumed RCCs undergoing conservative management. DESIGN: This
      was a retrospective cohort study. SETTING: The setting was a pituitary program at
      a university medical center. PARTICIPANTS: The participants were 75 patients with
      radiographically diagnosed RCCs. METHODS: All brain magnetic resonance imaging
      (MRI) scans performed at the University of Virginia from 2006 through 2013 were
      searched for the words "Rathke cleft cyst," and pituitary clinic notes from 2007
      to 2012 were reviewed for patients identified as probably having an RCC. Images
      for all patients were reviewed by the interpreting neuroradiologist, and those
      patients with at least 2 MRI scans were included. The dimensions of each cyst
      were assessed by the same neuroradiologist, and the volume of each cyst was
      analyzed as a function of the time from the first image obtained. RESULTS: A
      total of 75 patients (4-76 years old) met our inclusion criteria. The length of
      follow-up was 1 to 126 months (median 24 months). In 43 patients (57%) no
      detectable change in the size of their cysts was seen, in 21 patients (28%) cysts
      increased in size, and in 11 patients (15%) cysts decreased in size. The
      predicted mean cyst growth rate was not significantly different from 0.
      CONCLUSION: The increasingly prevalent use of brain imaging modalities such as
      MRI has resulted in an increase in the incidental discovery of pituitary lesions.
      Our study demonstrates that the majority of radiologically diagnosed RCCs remain
      unchanged or decrease in size over time. These results suggest that, in the
      absence of pressure symptoms, it is reasonable to manage patients with RCCs
      conservatively.

PMID- 26305623
TI  - Evaluation of the Postmortem Glucose and Glycogen Levels in Hepatic, Renal,
      Muscle, and Brain Tissues: Is It Possible to Estimate Postmortem Interval Using
      These Parameters?
AB  - The aim of our study was to investigate the postmortem levels of glucose and
      glycogen in hepatic, renal, muscle, and brain tissues and then examine the
      changes in those levels that could be useful for estimating postmortem interval.
      We established an animal model. Seventy female BALB/c albino mice were used in
      this study. After being sacrificed, the mice were randomly divided into six
      groups according to time elapsed since death (Group 1: 0 h; Group 2: 12 h; Group
      3: 24 h; Group 4: 36 h; Group 5: 48 h; and Group 6: 60 h). Glucose levels were
      significantly different between groups for all tissues studied. Slope of the
      change per unit time was higher for the hepatic glucose levels. Based on these
      results, it is possible to estimate postmortem interval using postmortem glucose
      levels in hepatic tissue. Tissue-specific assessment may contribute valuable
      information to postmortem interval studies. 

PMID- 26305622
TI  - Diurnal Cortisol Rhythm Is Associated With Adverse Cardiac Events and Mortality
      in Coronary Artery Bypass Patients.
AB  - PURPOSE: There is growing evidence that the hypothalamic-pituitary-adrenal axis
      plays a role in the progression of cardiovascular disease. We examined the
      relationship between diurnal cortisol rhythm and adverse events in patients
      undergoing coronary artery bypass graft (CABG) surgery. We hypothesized that a
      flatter presurgical diurnal cortisol slope would be associated with higher rates
      of adverse cardiac events and death in the years following the CABG procedure.
      METHODS: Repeated measures of saliva were taken over the day from 250 CABG
      patients 1 month before surgery to assess diurnal cortisol slope and overall
      output (area under the curve). Long-term clinical outcomes were occurrence of a
      major adverse cardiac event (MACE) and death, and were collected up to 2.68 (SD =
      0.40) years after surgery. Cox proportional hazard models were used to determine
      relationships between presurgical cortisol and clinical outcomes. EuroSCORE,
      chronic illness burden, and whether or not the patient had undergone
      cardiopulmonary bypass were included as covariates in the models. RESULTS:
      Diurnal cortisol slope predicted the occurrence of MACE or death after surgery
      (hazard ratio = 0.73; 95% confidence interval = 0.56-0.96; P = .023). Patients
      with a steeper slope were at reduced risk of adverse outcomes. This association
      was driven by changes in both waking and evening cortisol levels. CONCLUSION:
      These results provide evidence for a link between diurnal cortisol rhythm and
      recovery after CABG. Measuring diurnal cortisol slope before surgery may help to
      identify those patients at risk of adverse outcomes in the years after the
      procedure.

PMID- 26305624
TI  - The rural-urban effect on spatial genetic structure of type II Toxoplasma gondii
      strains involved in human congenital toxoplasmosis, France, 2002-2009.
AB  - Congenital toxoplasmosis involves Toxoplasma gondii type II strains in 95% of
      cases in France. We used spatial principal component analysis (sPCA) and 15
      microsatellite markers to investigate the spatial genetic structure of type II
      strains involved in 240 cases of congenital toxoplasmosis in France from 2002
      through 2009. Mailing addresses of patients were geo-referenced a posteriori in
      decimal degrees and categorized into urban or rural areas of residence. No
      spatial genetic structure was found for type II strains that infected mothers who
      were living in urban areas, but a global spatial genetic structure was found for
      those that infected mothers who were living in a rural environment. Our results
      suggest that sources of infection by T. gondii are different in rural and urban
      areas in France, and advocate for targeted messages in the prevention of
      toxoplasmosis according to the type of residence of susceptible people. 

PMID- 26305625
TI  - Coxsackievirus B3 induces autophagy in HeLa cells via the AMPK/MEK/ERK and
      Ras/Raf/MEK/ERK signaling pathways.
AB  - In a previous study, the number of autophagosomes increased after coxsackievirus
      B3 (CVB3) infection. However, the exact mechanism by which CVB3 regulates the
      number of autophagosomes is unclear. Earlier studies have found that infection
      with CVB3 activates extracellular signal-regulated kinase (ERK). ERK is essential
      for CVB3 replication and can increase the number of autophagosomes. In the
      current study, extracellular signal-regulated kinase 1/2 was activated in HeLa
      cells after CVB3 infection. The ERK kinase inhibitor, U0126, was then used to
      inhibit the activity of ERK. Treatment with U0126 led to a significant reduction
      in the number of autophagosomes indicating that the CVB3-induced autophagosome
      accumulation may have occurred via the ERK pathway. The relationship between CVB3
      infection and ERK pathway activation was also investigated. The results showed
      that the RasGAP protein could be further cleaved, leading to the activation of
      the Ras/Raf/MEK (mitogen/extracellular signal-regulated kinase)/ERK pathway and
      that CVB3 infection could result in an increase in the concentration of calcium
      in the cytoplasm, resulting in mitochondrial damage, a decrease in the
      concentration of ATP and activation of the AMPK (AMP-activated protein
      kinase)/MEK/ERK pathway. In summary, CVB3 might directly or indirectly induce
      autophagy via AMPK/MEK/ERK and Ras/Raf/MEK/ERK signaling pathways in the host
      cells, representing a pivotal mechanism for CVB3 pathogenesis. 

PMID- 26305626
TI  - Treating Pain in Dementia--Are We Good Enough?
AB  - Up to 80% of nursing home residents may be experiencing pain; however, in many
      cases their pain is not diagnosed and/or treated. People with moderate to severe
      dementia may have impaired communication, and this can impact on their self
      report of pain. Drug treatment should be used cautiously. --This report is
      adapted from paineurope 2015; Issue 1, (c)Haymarket Medical Publications Ltd.,
      and is presented with permission. paineurope is provided as a service to pain
      management by Mundipharma International, Ltd., and is distributed free of charge
      to health care professionals in Europe. Archival issues can be viewed via the Web
      site: www.paineurope.com , at which health professionals can find links to the
      original articles and request copies of the quarterly publication and access
      additional pain education and pain management resources.

PMID- 26305627
TI  - Insights into electrochemical reactions from ambient pressure photoelectron
      spectroscopy.
AB  - The understanding of fundamental processes in the bulk and at the interfaces of
      electrochemical devices is a prerequisite for the development of new technologies
      with higher efficiency and improved performance. One energy storage scheme of
      great interest is splitting water to form hydrogen and oxygen gas and converting
      back to electrical energy by their subsequent recombination with only water as a
      byproduct. However, kinetic limitations to the rate of oxygen-based
      electrochemical reactions hamper the efficiency in technologies such as solar
      fuels, fuel cells, and electrolyzers. For these reactions, the use of metal
      oxides as electrocatalysts is prevalent due to their stability, low cost, and
      ability to store oxygen within the lattice. However, due to the inherently
      convoluted nature of electrochemical and chemical processes in electrochemical
      systems, it is difficult to isolate and study individual electrochemical
      processes in a complex system. Therefore, in situ characterization tools are
      required for observing related physical and chemical processes directly at the
      places where and while they occur and can help elucidate the mechanisms of charge
      separation and charge transfer at electrochemical interfaces. X-ray photoelectron
      spectroscopy (XPS), also known as ESCA (electron spectroscopy for chemical
      analysis), has been used as a quantitative spectroscopic technique that measures
      the elemental composition, as well as chemical and electronic state of a
      material. Building from extensive ex situ characterization of electrochemical
      systems, initial in situ studies were conducted at or near ultrahigh vacuum (UHV)
      conditions (<=10(-6) Torr) to probe solid-state electrochemical systems. However,
      through the integration of differential-pumping stages, XPS can now operate at
      pressures in the torr range, comprising a technique called ambient pressure XPS
      (AP-XPS). In this Account, we briefly review the working principles and current
      status of AP-XPS. We use several recent in situ studies on model electrochemical
      components as well as operando studies performed by our groups at the Advanced
      Light Source (ALS) at Lawrence Berkeley National Laboratory to illustrate that AP
      XPS is both a chemically and an electrically specific tool since photoelectrons
      carry information on both the local chemistry and electrical potentials. The
      applications of AP-XPS to oxygen electrocatalysis shown in this Account span well
      defined studies of (1) the oxide/oxygen gas interface, (2) the oxide/water vapor
      interface, and (3) operando measurements of half and full electrochemical cells.
      Using specially designed model devices, we can expose and isolate the electrode
      or interface of interest to the incident X-ray beam and AP-XPS analyzer to relate
      the electrical potentials to the composition/chemical state of the key components
      and interfaces. We conclude with an outlook on new developments of AP-XPS end
      stations, which may provide significant improvement in the observation of
      dynamics over a wide range of time scales, higher spatial resolution, and
      improved characterization of boundary or interface layers (solid/solid and
      liquid/solid). 

PMID- 26305628
TI  - Trading Later Rewards for Current Pleasure: Pornography Consumption and Delay
      Discounting.
AB  - Internet pornography is a multi-billion-dollar industry that has grown
      increasingly accessible. Delay discounting involves devaluing larger, later
      rewards in favor of smaller, more immediate rewards. The constant novelty and
      primacy of sexual stimuli as particularly strong natural rewards make Internet
      pornography a unique activator of the brain's reward system, thereby having
      implications for decision-making processes. Based on theoretical studies of
      evolutionary psychology and neuroeconomics, two studies tested the hypothesis
      that consuming Internet pornography would relate to higher rates of delay
      discounting. Study 1 used a longitudinal design. Participants completed a
      pornography use questionnaire and a delay discounting task at Time 1 and then
      again four weeks later. Participants reporting higher initial pornography use
      demonstrated a higher delay discounting rate at Time 2, controlling for initial
      delay discounting. Study 2 tested for causality with an experimental design.
      Participants were randomly assigned to abstain from either their favorite food or
      pornography for three weeks. Participants who abstained from pornography use
      demonstrated lower delay discounting than participants who abstained from their
      favorite food. The finding suggests that Internet pornography is a sexual reward
      that contributes to delay discounting differently than other natural rewards.
      Theoretical and clinical implications of these studies are highlighted.

PMID- 26305629
TI  - Evaluation of Escherichia coli viability by flow cytometry; a method for
      determining bacterial responses to antibiotic exposure.
AB  - BACKGROUND:  In this study, we check for the presence of specific resistance
      genes by PCR and then we used flow cytometry to evaluate antibiotic-induced
      effects in different strains of Escherichia coli. METHODS:  The presence of
      resistance genes was investigated by PCR in 10 strains of Escherichia coli
      isolated from Foglia River. Bacterial responses to different antibiotics were
      also tested with flow cytometry techniques by evaluating both the degree of
      decrease in viability and the light scatter changes in all of the strains.
      RESULTS:  PCR revealed that only one strain exhibits the presence of one
      resistance gene. Despite this, analyses of strains using flow cytometry evidenced
      the presence of viable subpopulations after antibiotic treatment. Furthermore,
      analyses of scatter signals revealed profound changes in the Forward Scatter
      (FSC) and Side Scatter (SSC) of the bacterial populations as a consequence of
      antibiotic exposure, confirming the viability and membrane potential data. The
      riverine strains were in general less sensitive to antibiotics than the reference
      strain (ATCC 25922). CONCLUSIONS:  Antibiotic resistance is a widespread
      phenomena. The multiparametric approach based on flow cytometry used in this
      study, providing results about different aspects (cell viability, membrane
      potential, light scatter changes), may overcome the limitation of PCR and could
      represent an adequate method for the evaluation of bacteria responses to
      antibiotic exposure. This article is protected by copyright. All rights reserved.

PMID- 26305630
TI  - A Hierarchical Particle-Shell Architecture for Long-Term Cycle Stability of Li2S
      Cathodes.
AB  - A hierarchical particle-shell architecture for long-term cycle stability of Li2S
      cathodes is described. Multiscale and multilevel protection prevents mechanical
      degradation and polysulfide dissolution in lithium-sulfur battery chemistries.

PMID- 26305631
TI  - Association Between Changes in Serum 5-Hydroxy-Tryptamine Concentrations and
      Improvement in Clinical Symptoms in Primary Premature Ejaculation with Paroxetine
      Treatment.
AB  - BACKGROUND: This study aimed to investigate the association between changes in
      serum 5-hydroxy tryptamine (5-HT) concentrations and improvement in clinical
      symptoms in primary premature ejaculation with paroxetine treatment. MATERIAL AND
      METHODS: A total of 142 men aged 18-65 years with a history of lifelong premature
      ejaculation and an intravaginal ejaculation latency time (IELT) <120 s were
      included in this study. Patients were divided into 3 groups according to IELT:
      IELT <=30 s (group A), (IELT >30 s and <=60 s (group B), and IELT >60 s and <120
      s (group C). Patients in the 3 groups were administered paroxetine hydrochloride
      20 mg/d for 8 weeks. Blood samples were obtained from the candidates in the
      screening period and after 8 weeks of treatment. Plasma 5-hydroxy-tryptamine (5
      HT) concentrations were measured by enzyme-linked immunosorbent assay. RESULTS:
      Reliable data from 125 patients were obtained. There were 41 patients in group A,
      40 in group B, and 44 in Group C. IELT and serum 5-HT concentrations were
      significantly improved in the 3 groups after treatment (all P<0.001). The mean
      change and fold increase in IELT and the mean change in serum 5-HT concentrations
      in group A were significantly higher than those in groups B and C (all P<0.001).
      The mean change and fold increase in IELT and the mean change in serum 5-HT
      concentrations in group B were significantly higher than those in group C (all
      P<0.001). Significantly more patients in group A achieved clinical benefits than
      those in groups B and C (P<0.001). CONCLUSIONS: Improvement in serum 5-HT
      concentrations has obvious association with primary premature ejaculation symptom
      improvement with paroxetine use.

PMID- 26305634
TI  - Mahabalipooram: Edward Lear.

PMID- 26305643
TI  - Fusing Randomized Trials With Big Data: The Key to Self-learning Health Care
      Systems?

PMID- 26305644
TI  - A PIECE OF MY MIND. The "Good Person" Sign.

PMID- 26305645
TI  - Lifestyles and Cognitive Health: What Older Individuals Can Do to Optimize
      Cognitive Outcomes.

PMID- 26305646
TI  - Pediatric Pulseless Arrest With "Nonshockable" Rhythm: Does Faster Time to
      Epinephrine Improve Outcome?

PMID- 26305647
TI  - Next-Generation Sequencing and Detection of Minimal Residual Disease in Acute
      Myeloid Leukemia: Ready for Clinical Practice?

PMID- 26305649
TI  - Effect of Omega-3 Fatty Acids, Lutein/Zeaxanthin, or Other Nutrient
      Supplementation on Cognitive Function: The AREDS2 Randomized Clinical Trial.
AB  - IMPORTANCE: Observational data have suggested that high dietary intake of
      saturated fat and low intake of vegetables may be associated with increased risk
      of Alzheimer disease. OBJECTIVE: To test the effects of oral supplementation with
      nutrients on cognitive function. DESIGN, SETTING, AND PARTICIPANTS: In a double
      masked randomized clinical trial (the Age-Related Eye Disease Study 2 [AREDS2]),
      retinal specialists in 82 US academic and community medical centers enrolled and
      observed participants who were at risk for developing late age-related macular
      degeneration (AMD) from October 2006 to December 2012. In addition to annual eye
      examinations, several validated cognitive function tests were administered via
      telephone by trained personnel at baseline and every 2 years during the 5-year
      study. INTERVENTIONS: Long-chain polyunsaturated fatty acids (LCPUFAs) (1 g)
      and/or lutein (10 mg)/zeaxanthin (2 mg) vs placebo were tested in a factorial
      design. All participants were also given varying combinations of vitamins C, E,
      beta carotene, and zinc. MAIN OUTCOMES AND MEASURES: The main outcome was the
      yearly change in composite scores determined from a battery of cognitive function
      tests from baseline. The analyses, which were adjusted for baseline age, sex,
      race, history of hypertension, education, cognitive score, and depression score,
      evaluated the differences in the composite score between the treated vs untreated
      groups. The composite score provided an overall score for the battery, ranging
      from -22 to 17, with higher scores representing better function. RESULTS: A total
      of 89% (3741/4203) of AREDS2 participants consented to the ancillary cognitive
      function study and 93.6% (3501/3741) underwent cognitive function testing. The
      mean (SD) age of the participants was 72.7 (7.7) years and 57.5% were women.
      There were no statistically significant differences in change of scores for
      participants randomized to receive supplements vs those who were not. The yearly
      change in the composite cognitive function score was -0.19 (99% CI, -0.25 to 
      0.13) for participants randomized to receive LCPUFAs vs -0.18 (99% CI, -0.24 to 
      0.12) for those randomized to no LCPUFAs (difference in yearly change, -0.03 [99%
      CI, -0.20 to 0.13]; P = .63). Similarly, the yearly change in the composite
      cognitive function score was -0.18 (99% CI, -0.24 to -0.11) for participants
      randomized to receive lutein/zeaxanthin vs -0.19 (99% CI, -0.25 to -0.13) for
      those randomized to not receive lutein/zeaxanthin (difference in yearly change,
      0.03 [99% CI, -0.14 to 0.19]; P = .66). Analyses were also conducted to assess
      for potential interactions between LCPUFAs and lutein/zeaxanthin and none were
      found to be significant. CONCLUSIONS AND RELEVANCE: Among older persons with AMD,
      oral supplementation with LCPUFAs or lutein/zeaxanthin had no statistically
      significant effect on cognitive function. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00345176.

PMID- 26305652
TI  - Engaging Primary Care Clinicians in Early Obesity Prevention Research.

PMID- 26305653
TI  - Prostate Cancer Screening.

PMID- 26305648
TI  - Effect of a 24-Month Physical Activity Intervention vs Health Education on
      Cognitive Outcomes in Sedentary Older Adults: The LIFE Randomized Trial.
AB  - IMPORTANCE: Epidemiological evidence suggests that physical activity benefits
      cognition, but results from randomized trials are limited and mixed. OBJECTIVE:
      To determine whether a 24-month physical activity program results in better
      cognitive function, lower risk of mild cognitive impairment (MCI) or dementia, or
      both, compared with a health education program. DESIGN, SETTING, AND
      PARTICIPANTS: A randomized clinical trial, the Lifestyle Interventions and
      Independence for Elders (LIFE) study, enrolled 1635 community-living participants
      at 8 US centers from February 2010 until December 2011. Participants were
      sedentary adults aged 70 to 89 years who were at risk for mobility disability but
      able to walk 400 m. INTERVENTIONS: A structured, moderate-intensity physical
      activity program (n = 818) that included walking, resistance training, and
      flexibility exercises or a health education program (n = 817) of educational
      workshops and upper-extremity stretching. MAIN OUTCOMES AND MEASURES:
      Prespecified secondary outcomes of the LIFE study included cognitive function
      measured by the Digit Symbol Coding (DSC) task subtest of the Wechsler Adult
      Intelligence Scale (score range: 0-133; higher scores indicate better function)
      and the revised Hopkins Verbal Learning Test (HVLT-R; 12-item word list recall
      task) assessed in 1476 participants (90.3%). Tertiary outcomes included global
      and executive cognitive function and incident MCI or dementia at 24 months.
      RESULTS: At 24 months, DSC task and HVLT-R scores (adjusted for clinic site, sex,
      and baseline values) were not different between groups. The mean DSC task scores
      were 46.26 points for the physical activity group vs 46.28 for the health
      education group (mean difference, -0.01 points [95% CI, -0.80 to 0.77 points], P
      = .97). The mean HVLT-R delayed recall scores were 7.22 for the physical activity
      group vs 7.25 for the health education group (mean difference, -0.03 words [95%
      CI, -0.29 to 0.24 words], P = .84). No differences for any other cognitive or
      composite measures were observed. Participants in the physical activity group who
      were 80 years or older (n = 307) and those with poorer baseline physical
      performance (n = 328) had better changes in executive function composite scores
      compared with the health education group (P = .01 for interaction for both
      comparisons). Incident MCI or dementia occurred in 98 participants (13.2%) in the
      physical activity group and 91 participants (12.1%) in the health education group
      (odds ratio, 1.08 [95% CI, 0.80 to 1.46]). CONCLUSIONS AND RELEVANCE: Among
      sedentary older adults, a 24-month moderate-intensity physical activity program
      compared with a health education program did not result in improvements in global
      or domain-specific cognitive function. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT01072500.

PMID- 26305650
TI  - Time to Epinephrine and Survival After Pediatric In-Hospital Cardiac Arrest.
AB  - IMPORTANCE: Delay in administration of the first epinephrine dose is associated
      with decreased survival among adults after in-hospital, nonshockable cardiac
      arrest. Whether this association is true in the pediatric in-hospital cardiac
      arrest population remains unknown. OBJECTIVE: To determine whether time to first
      epinephrine dose is associated with outcomes in pediatric in-hospital cardiac
      arrest. DESIGN, SETTING AND PARTICIPANTS: We performed an analysis of data from
      the Get With the Guidelines-Resuscitation registry. We included US pediatric
      patients (age <18 years) with an in-hospital cardiac arrest and an initial
      nonshockable rhythm who received at least 1 dose of epinephrine. A total of 1558
      patients (median age, 9 months [interquartile range [IQR], 13 days-5 years]) were
      included in the final cohort. EXPOSURE: Time to epinephrine, defined as time in
      minutes from recognition of loss of pulse to the first dose of epinephrine. MAIN
      OUTCOMES AND MEASURES: The primary outcome was survival to hospital discharge.
      Secondary outcomes included return of spontaneous circulation (ROSC), survival at
      24 hours, and neurological outcome. A favorable neurological outcome was defined
      as a score of 1 to 2 on the Pediatric Cerebral Performance Category scale.
      RESULTS: Among the 1558 patients, 487 (31.3%) survived to hospital discharge. The
      median time to first epinephrine dose was 1 minute (IQR, 0-4; range, 0-20; mean
      [SD], 2.6 [3.4] minutes). Longer time to epinephrine administration was
      associated with lower risk of survival to discharge in multivariable analysis
      (multivariable-adjusted risk ratio [RR] per minute delay, 0.95 [95% CI, 0.93
      0.98]). Longer time to epinephrine administration was also associated with
      decreased risk of ROSC (multivariable-adjusted RR per minute delay, 0.97 [95% CI,
      0.96-0.99]), decreased risk of survival at 24 hours (multivariable-adjusted RR
      per minute delay, 0.97 [95% CI, 0.95-0.99]), and decreased risk of survival with
      favorable neurological outcome (multivariable-adjusted RR per minute delay, 0.95
      [95% CI, 0.91-0.99]). Patients with time to epinephrine administration of longer
      than 5 minutes (233/1558) compared with those with time to epinephrine of 5
      minutes or less (1325/1558) had lower risk of in-hospital survival to discharge
      (21.0% [49/233] vs 33.1% [438/1325]; multivariable-adjusted RR, 0.75 [95% CI,
      0.60-0.93]; P = .01). CONCLUSIONS AND RELEVANCE: Among children with in-hospital
      cardiac arrest with an initial nonshockable rhythm who received epinephrine,
      delay in administration of epinephrine was associated with decreased chance of
      survival to hospital discharge, ROSC, 24-hour survival, and survival to hospital
      discharge with a favorable neurological outcome.

PMID- 26305654
TI  - Clinical Significance of a Positive Antinuclear Antibody Test.

PMID- 26305655
TI  - Military Misconduct and Homelessness Among US Veterans Separated From Active
      Duty, 2001-2012.

PMID- 26305651
TI  - Association Between Mutation Clearance After Induction Therapy and Outcomes in
      Acute Myeloid Leukemia.
AB  - IMPORTANCE: Tests that predict outcomes for patients with acute myeloid leukemia
      (AML) are imprecise, especially for those with intermediate risk AML. OBJECTIVES:
      To determine whether genomic approaches can provide novel prognostic information
      for adult patients with de novo AML. DESIGN, SETTING, AND PARTICIPANTS: Whole
      genome or exome sequencing was performed on samples obtained at disease
      presentation from 71 patients with AML (mean age, 50.8 years) treated with
      standard induction chemotherapy at a single site starting in March 2002, with
      follow-up through January 2015. In addition, deep digital sequencing was
      performed on paired diagnosis and remission samples from 50 patients (including
      32 with intermediate-risk AML), approximately 30 days after successful induction
      therapy. Twenty-five of the 50 were from the cohort of 71 patients, and 25 were
      new, additional cases. EXPOSURES: Whole-genome or exome sequencing and targeted
      deep sequencing. Risk of identification based on genetic data. MAIN OUTCOMES AND
      MEASURES: Mutation patterns (including clearance of leukemia-associated variants
      after chemotherapy) and their association with event-free survival and overall
      survival. RESULTS: Analysis of comprehensive genomic data from the 71 patients
      did not improve outcome assessment over current standard-of-care metrics. In an
      analysis of 50 patients with both presentation and documented remission samples,
      24 (48%) had persistent leukemia-associated mutations in at least 5% of bone
      marrow cells at remission. The 24 with persistent mutations had significantly
      reduced event-free and overall survival vs the 26 who cleared all mutations.
      Patients with intermediate cytogenetic risk profiles had similar findings.
      [table: see text]. CONCLUSIONS AND RELEVANCE: The detection of persistent
      leukemia-associated mutations in at least 5% of bone marrow cells in day 30
      remission samples was associated with a significantly increased risk of relapse,
      and reduced overall survival. These data suggest that this genomic approach may
      improve risk stratification for patients with AML.

PMID- 26305656
TI  - Opioid Dependence Treatment in the Emergency Department.

PMID- 26305657
TI  - Opioid Dependence Treatment in the Emergency Department--Reply.

PMID- 26305658
TI  - Etiologies of Tattoo Lesions.

PMID- 26305659
TI  - Etiologies of Tattoo Lesions--Reply.

PMID- 26305660
TI  - Incorrect Values Reported.

PMID- 26305661
TI  - Incorrect Study Name.

PMID- 26305662
TI  - Lines Omitted From Table.

PMID- 26305664
TI  - The House: Its Unique Problems in Hygiene. 1915.

PMID- 26305665
TI  - JAMA PATIENT PAGE. Childhood Obesity.

PMID- 26305666
TI  - VA Telemedicine: An Analysis of Cost and Time Savings.
AB  - INTRODUCTION: The Veterans Affairs (VA) healthcare system provides beneficiary
      travel reimbursement ("travel pay") to qualifying patients for traveling to
      appointments. Travel pay is a large expense for the VA and hence the U.S.
      Government, projected to cost nearly $1 billion in 2015. Telemedicine in the VA
      system has the potential to save money by reducing patient travel and thus the
      amount of travel pay disbursed. In this study, we quantify this savings and also
      report trends in VA telemedicine volumes over time. MATERIALS AND METHODS: All
      telemedicine visits based at the VA Hospital in White River Junction, VT between
      2005 and 2013 were reviewed (5,695 visits). Travel distance and time saved as a
      result of telemedicine were calculated. Clinical volume in the mental health
      department, which has had the longest participation in telemedicine, was
      analyzed. RESULTS: Telemedicine resulted in an average travel savings of 145
      miles and 142 min per visit. This led to an average travel payment savings of
      $18,555 per year. Telemedicine volume grew significantly over the study period
      such that by the final year the travel pay savings had increased to $63,804, or
      about 3.5% of the total travel pay disbursement for that year. The number of
      mental health telemedicine visits rose over the study period but remained small
      relative to the number of face-to-face visits. A higher proportion of
      telemedicine visits involved new patients. CONCLUSIONS: Telemedicine at the VA
      saves travel distance and time, although the reduction in travel payments remains
      modest at current telemedicine volumes.

PMID- 26305667
TI  - Budget impact of incorporating one instillation of hexaminolevulinate
      hydrochloride blue-light cytoscopy in transurethral bladder tumour resection for
      patients with non-muscle-invasive bladder cancer in Sweden.
AB  - OBJECTIVES: To explore the cost impact on Swedish healthcare of incorporating one
      instillation of hexaminolevulinate hydrochloride (HAL) blue-light cystoscopy into
      transurethral resection of bladder tumour (TURBT) in patients with suspected new
      or recurrent non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: A
      decision tree model was built based on European Association of Urology guidelines
      for the treatment and management of NMIBC. Input data were compiled from two
      recent studies comparing recurrence rates of bladder cancer in patients
      undergoing TURBT with either the current standard of care (SOC) of white-light
      cystoscopy, or with the SOC and HAL blue-light cystoscopy. Using these published
      data with clinical cost data for surgical and outpatient procedures and
      pharmaceutical costs, the model reported on the clinical and economic differences
      associated with the two treatment options. RESULTS: This model demonstrates the
      significant clinical benefits likely to be observed through the incorporation of
      HAL blue-light cystoscopy for TURBT in terms of reductions in recurrences of
      bladder cancer. Analysis of economic outputs of the model found that the use of
      one instillation of HAL for TURBT in all Swedish patients with NMIBC is likely to
      be cost-neutral or cost-saving over 5 years relative to the current SOC of white
      light cystoscopy. CONCLUSIONS: The results of this analysis provide additional
      health economic rationale for the incorporation of a single instillation of HAL
      blue-light cystoscopy for TURBT in the treatment of patients with NMIBC in
      Sweden.

PMID- 26305668
TI  - The Relationship between Vascular Endothelial Growth Factor 1154G/A Polymorphism
      and Recurrent Implantation Failure.
AB  - OBJECTIVE: The aim of this study was to investigate the relationship between
      herpesvirus-associated ubiquitin-specific protease (HAUSP A/G, rs1529916), tumor
      protein p53 (TP53 Arg/Pro, rs1042522), leukemia inhibitory factor (LIF G/T,
      rs929271), glycoprotein 130 (gp130 A/T, rs1900173) and vascular endothelial
      growth factor (VEGF G/A, rs1570360) polymorphisms and recurrent implantation
      failure (RIF) in Brazilian women. SUBJECTS AND METHODS: A total of 120 women with
      RIF (i.e. those with >=5 cleaved embryos transferred and a minimum of 2 failed in
      vitro fertilization/intracytoplasmic sperm injection attempts) were included. The
      control group involved 89 women who had experienced at least 1 live birth
      (without any infertility treatment). DNA was extracted from the peripheral blood
      of all participants, and the abovementioned single-nucleotide polymorphisms
      (SNPs) were genotyped by real-time polymerase chain reaction. The data were
      evaluated using Fisher's test. RESULTS: A significant difference between the RIF
      and control groups was found in the VEGF gene where the GG genotype showed a 2.1
      fold increased chance of not being included in the RIF group, while the presence
      of an A allele increased this risk 1.6-fold. No significant differences were
      found for the other polymorphisms. CONCLUSION: This study showed an association
      between the VEGF -1154G/A polymorphism and RIF in Brazilian women.

PMID- 26305670
TI  - Dose-volume histogram prediction using density estimation.
AB  - Knowledge of what dose-volume histograms can be expected for a previously unseen
      patient could increase consistency and quality in radiotherapy treatment
      planning. We propose a machine learning method that uses previous treatment plans
      to predict such dose-volume histograms. The key to the approach is the framing of
      dose-volume histograms in a probabilistic setting.The training consists of
      estimating, from the patients in the training set, the joint probability
      distribution of some predictive features and the dose. The joint distribution
      immediately provides an estimate of the conditional probability of the dose given
      the values of the predictive features. The prediction consists of estimating,
      from the new patient, the distribution of the predictive features and
      marginalizing the conditional probability from the training over this.
      Integrating the resulting probability distribution for the dose yields an
      estimate of the dose-volume histogram.To illustrate how the proposed method
      relates to previously proposed methods, we use the signed distance to the target
      boundary as a single predictive feature. As a proof-of-concept, we predicted dose
      volume histograms for the brainstems of 22 acoustic schwannoma patients treated
      with stereotactic radiosurgery, and for the lungs of 9 lung cancer patients
      treated with stereotactic body radiation therapy. Comparing with two previous
      attempts at dose-volume histogram prediction we find that, given the same input
      data, the predictions are similar.In summary, we propose a method for dose-volume
      histogram prediction that exploits the intrinsic probabilistic properties of dose
      volume histograms. We argue that the proposed method makes up for some
      deficiencies in previously proposed methods, thereby potentially increasing ease
      of use, flexibility and ability to perform well with small amounts of training
      data. 

PMID- 26305669
TI  - Cyclophilin A as a potential genetic adjuvant to improve HIV-1 Gag DNA vaccine
      immunogenicity by eliciting broad and long-term Gag-specific cellular immunity in
      mice.
AB  - Previous research has shown that host Cyclophilin A (CyPA) can promote dendritic
      cell maturation and the subsequent innate immune response when incorporated into
      an HIV-1 Gag protein to circumvent the resistance of dendritic cells to HIV-1
      infection. This led us to hypothesize that CyPA may improve HIV-1 Gag-specific
      vaccine immunogenicity via binding with Gag antigen. The adjuvant effect of CyPA
      was evaluated using a DNA vaccine with single or dual expression cassettes. Mouse
      studies indicated that CyPA specifically and markedly promoted HIV-1 Gag-specific
      cellular immunity but not an HIV-1 Env-specific cellular response. The Gag/CyPA
      dual expression cassettes stimulated a greater Gag-specific cellular immune
      response, than Gag immunization alone. Furthermore, CyPA induced a broad Gag
      specific T cell response and strong cellular immunity that lasted up to 5 months.
      In addition, CyPA skewed to cellular rather than humoral immunity. To investigate
      the mechanisms of the adjuvant effect, site-directed mutagenesis in CyPA,
      including active site residues H54Q and F60A resulted in mutants that were co
      expressed with Gag in dual cassettes. The immune response to this vaccine was
      analyzed in vivo. Interestingly, the wild type CyPA markedly increased Gag
      cellular immunity, but the H54Q and F60A mutants drastically reduced CyPA
      adjuvant activation. Therefore, we suggest that the adjuvant effect of CyPA was
      based on Gag-CyPA-specific interactions. Herein, we report that Cyclophilin A can
      augment HIV-1 Gag-specific cellular immunity as a genetic adjuvant in multiplex
      DNA immunization strategies, and that activity of this adjuvant is specific,
      broad, long-term, and based on Gag-CyPA interaction. 

PMID- 26305671
TI  - Classical complement pathway activation in immune thrombocytopenia purpura:
      inhibition by a novel C1s inhibitor.

PMID- 26305672
TI  - Age-Related Changes in Pre- and Postsynaptic Partners of the Cholinergic C
      Boutons in Wild-Type and SOD1G93A Lumbar Motoneurons.
AB  - Large cholinergic synaptic terminals known as C-boutons densely innervate the
      soma and proximal dendrites of motoneurons that are prone to neurodegeneration in
      amyotrophic lateral sclerosis (ALS). Studies using the Cu/Zn-superoxide dismutase
      (SOD1) mouse model of ALS have generated conflicting data regarding C-bouton
      alterations exhibited during ALS pathogenesis. In the present work, a
      longitudinal study combining immunohistochemistry, biochemical approaches and
      extra- and intra-cellular electrophysiological recordings revealed that the whole
      spinal cholinergic system is modified in the SOD1 mouse model of ALS compared to
      wild type (WT) mice as early as the second postnatal week. In WT motoneurons,
      both C-bouton terminals and associated M2 postsynaptic receptors presented a
      complex age-related dynamic that appeared completely disrupted in SOD1
      motoneurons. Indeed, parallel to C-bouton morphological alterations, analysis of
      confocal images revealed a clustering process of M2 receptors during WT
      motoneuron development and maturation that was absent in SOD1 motoneurons. Our
      data demonstrated for the first time that the lamina X cholinergic interneurons,
      the neuronal source of C-boutons, are over-abundant in high lumbar segments in
      SOD1 mice and are subject to neurodegeneration in the SOD1 animal model. Finally,
      we showed that early C-bouton system alterations have no physiological impact on
      the cholinergic neuromodulation of newborn motoneurons. Altogether, these data
      suggest a complete reconfiguration of the spinal cholinergic system in SOD1
      spinal networks that could be part of the compensatory mechanisms established
      during spinal development. 

PMID- 26305673
TI  - Stromal expression of ALDH1 in human breast carcinomas indicates reduced tumor
      progression.
AB  - Interactions between cancer cells and microenvironment are emerging issue in
      tumor progression. Aldehyde dehydrogenase 1 (ALDH1) is a recognized cancer stem
      cell marker but little is known about its role in intratumoral stroma. Therefore,
      we focused on ALDH1 expression in tumor-associated stroma of breast carcinomas
      (BrCa). Stromal and tumoral ALDH1 expression was evaluated immunohistochemically
      in BrCa and their lymph node metastases (LNMs), and related to clinico
      pathological characteristics, patients' outcome, presence of CD68, HLADR,
      retinoic acid (RA) in stroma, and selected proteins in tumor cells. ALDH1(+)
      stromal cells were detected in 53% of 374 BrCa and 61% of 102 LNMs. ALDH1(+)
      stroma in primary tumor correlated to longer disease-free (p = 0.030), metastasis
      free (p = 0.024), and overall survival (p = 0.043) having an independent
      prognostic impact on DFS (multivariate analysis, p = 0.047). It was associated
      with concomitant presence of HLA-DR(+) stromal cells and RA in tumor cells (both
      p < 0.001), and inversely associated with vimentin expression in tumor cells (p =
      0.036). ALDH1(+) stroma in LNMs correlated inversely to presence of disseminated
      tumor cells in patients' bone marrow (p = 0.014) and was independent
      prognosticator of shorter DFS and MFS (multivariate analysis, p = 0.004 and p =
      0.002, respectively). In conclusion, ALDH1 expression in tumor-associated stromal
      cells indicates reduced BrCa progression, possibly via RA secretion. 

PMID- 26305674
TI  - Construction and analysis of lncRNA-lncRNA synergistic networks to reveal
      clinically relevant lncRNAs in cancer.
AB  - Long non-coding RNAs (lncRNAs) play key roles in diverse biological processes.
      Moreover, the development and progression of cancer often involves the combined
      actions of several lncRNAs. Here we propose a multi-step method for constructing
      lncRNA-lncRNA functional synergistic networks (LFSNs) through co-regulation of
      functional modules having three features: common coexpressed genes of lncRNA
      pairs, enrichment in the same functional category and close proximity within
      protein interaction networks. Applied to three cancers, we constructed cancer
      specific LFSNs and found that they exhibit a scale free and modular architecture.
      In addition, cancer-associated lncRNAs tend to be hubs and are enriched within
      modules. Although there is little synergistic pairing of lncRNAs across cancers,
      lncRNA pairs involved in the same cancer hallmarks by regulating same or
      different biological processes. Finally, we identify prognostic biomarkers within
      cancer lncRNA expression datasets using modules derived from LFSNs. In summary,
      this proof-of-principle study indicates synergistic lncRNA pairs can be
      identified through integrative analysis of genome-wide expression data sets and
      functional information. 

PMID- 26305675
TI  - LincRNA-p21 activates endoplasmic reticulum stress and inhibits hepatocellular
      carcinoma.
AB  - LincRNA-p21 is a downstream long non-coding RNA (lncRNA) transcript of p53.
      LincRNA-p21 serves as a repressor in p53-dependent transcriptional responses and
      participates in diverse biological processes, including apoptosis, cell cycle,
      metabolism and pluripotency. However, the role of lincRNA-p21 in human
      hepatocellular carcinoma remains to be defined. Here in this work, we
      demonstrated that lincRNA-p21 acted as a tumor suppressive lncRNA in human
      hepatocellular carcinoma. We firstly found the downregulation of lincRNA-p21
      level in human hepatocellular carcinoma tissues, and showed that low expression
      of lincRNA-p21 was associated with high disease stage and predicted poor
      survival. Further we showed that lincRNA-p21 knockdown promoted proliferation and
      colony formation of HepG2, Huh7 and Bel-7042 cells in vitro, while lincRNA-p21
      overexpression obtained oppose results. Using tumor xenograft experiments, we
      also demonstrated that lincRNA-p21 inhibited HepG2 cell growth in vivo and
      lincRNA-p21 contributed to sorafenib-induced growth regression of HepG2 cell in
      vivo. Further mechanism analysis revealed that lincRNA-p21 promoted ER stress
      both in vitro and in vivo, which facilitated apoptosis of hepatocellular
      carcinoma cells. Finally, we demonstrated that ER stress accounted for lincRNA
      p21 effects on apoptosis, proliferation and in vivo growth of hepatocellular
      carcinoma. These findings implicate that lincRNA-p21 is a potential prognostic
      factor and therapeutic target for human hepatocellular carcinoma. 

PMID- 26305676
TI  - ZIP4 silencing improves bone loss in pancreatic cancer.
AB  - Metabolic bone disorders are associated with several types of human cancers.
      Pancreatic cancer patients usually suffer from severe nutrition deficiency,
      muscle wasting, and loss of bone mass. We have previously found that silencing of
      a zinc transporter ZIP4 prolongs the survival and reduces the severity of the
      cachexia in vivo. However, the role of ZIP4 in the pancreatic cancer related bone
      loss remains unknown. In this study we investigated the effect of ZIP4 knockdown
      on the bone structure, composition and mechanical properties of femurs in an
      orthotopic xenograft mouse model. Our data showed that silencing of ZIP4 resulted
      in increased bone tissue mineral density, decreased bone crystallinity and
      restoration of bone strength through the RANK/RANKL pathway. The results further
      support the impact of ZIP4 on the progression of pancreatic cancer, and suggest
      its potential significance as a therapeutic target for treating patients with
      such devastating disease and cancer related disorders. 

PMID- 26305678
TI  - Improved Environmental Life Cycle Assessment of Crop Production at the Catchment
      Scale via a Process-Based Nitrogen Simulation Model.
AB  - One of the major challenges in environmental life cycle assessment (LCA) of crop
      production is the nonlinearity between nitrogen (N) fertilizer inputs and on-site
      N emissions resulting from complex biogeochemical processes. A few studies have
      addressed this nonlinearity by combining process-based N simulation models with
      LCA, but none accounted for nitrate (NO3(-)) flows across fields. In this study,
      we present a new method, TNT2-LCA, that couples the topography-based simulation
      of nitrogen transfer and transformation (TNT2) model with LCA, and compare the
      new method with a current LCA method based on a French life cycle inventory
      database. Application of the two methods to a case study of crop production in a
      catchment in France showed that, compared to the current method, TNT2-LCA allows
      delineation of more appropriate temporal limits when developing data for on-site
      N emissions associated with specific crops in this catchment. It also improves
      estimates of NO3(-) emissions by better consideration of agricultural practices,
      soil-climatic conditions, and spatial interactions of NO3(-) flows across fields,
      and by providing predicted crop yield. The new method presented in this study
      provides improved LCA of crop production at the catchment scale. 

PMID- 26305677
TI  - Targeted or whole genome sequencing of formalin fixed tissue samples: potential
      applications in cancer genomics.
AB  - Current genomic studies are limited by the poor availability of fresh-frozen
      tissue samples. Although formalin-fixed diagnostic samples are in abundance, they
      are seldom used in current genomic studies because of the concern of formalin
      fixation artifacts. Better characterization of these artifacts will allow the use
      of archived clinical specimens in translational and clinical research studies. To
      provide a systematic analysis of formalin-fixation artifacts on Illumina
      sequencing, we generated 26 DNA sequencing data sets from 13 pairs of matched
      formalin-fixed paraffin-embedded (FFPE) and fresh-frozen (FF) tissue samples. The
      results indicate high rate of concordant calls between matched FF/FFPE pairs at
      reference and variant positions in three commonly used sequencing approaches
      (whole genome, whole exome, and targeted exon sequencing). Global mismatch rates
      and C . G > T . A substitutions were comparable between matched FF/FFPE samples,
      and discordant rates were low (<0.26%) in all samples. Finally, low-pass whole
      genome sequencing produces similar pattern of copy number alterations between
      FF/FFPE pairs. The results from our studies suggest the potential use of
      diagnostic FFPE samples for cancer genomic studies to characterize and catalog
      variations in cancer genomes.

PMID- 26305679
TI  - Identification of a Novel Coregulator, SH3YL1, That Interacts With the Androgen
      Receptor N-Terminus.
AB  - Nuclear receptor (NR)-mediated transcriptional activity is a dynamic process that
      is regulated by the binding of ligands that induce distinct conformational
      changes in the NR. These structural alterations lead to the differential
      recruitment of coregulators (coactivators or corepressors) that control the
      expression of NR-regulated genes. Here, we show that a stretch of proline
      residues located within the N-terminus of androgen receptor (AR) is a bona fide
      coregulator binding surface, the disruption of which reduces the androgen
      dependent proliferation and migration of prostate cancer (PCa) cells. Using T7
      phage display, we identified a novel AR-interacting protein, Src homology 3 (SH3)
      domain containing, Ysc84-like 1 (SH3YL1), whose interaction with the receptor is
      dependent upon this polyproline domain. As with mutations within the AR
      polyproline domain, knockdown of SH3YL1 attenuated androgen-mediated cell growth
      and migration. RNA expression analysis revealed that SH3YL1 was required for the
      induction of a subset of AR-modulated genes. Notable was the observation that
      ubinuclein 1 (UBN1), a key member of a histone H3.3 chaperone complex, was a
      transcriptional target of the AR/SH3YL1 complex, correlated with aggressive PCa
      in patients, and was necessary for the maximal androgen-mediated proliferation
      and migration of PCa cells. Collectively, these data highlight the importance of
      an amino-terminal activation domain, its associated coregulator, and downstream
      transcriptional targets in regulating cellular processes of pathological
      importance in PCa. 

PMID- 26305680
TI  - Height at Late Adolescence and Incident Diabetes among Young Men.
AB  - BACKGROUND: Short stature was suggested as a risk factor for diabetes onset among
      middle age individuals, but whether this is the case among young adults is
      unclear. Our goal was to assess the association between height and incident
      diabetes among young men. METHODS AND FINDINGS: Incident diabetes was assessed
      among 32,055 men with no history of diabetes, from the prospectively followed
      young adults of the MELANY cohort. Height was measured at two time points; at
      adolescence (mean age 17.4+/-0.3 years) and grouped according to the US-CDC
      percentiles and at young adulthood (mean age 31.0+/-5.6 years). Cox proportional
      hazards models were applied. There were 702 new cases of diabetes during a mean
      follow-up of 6.3+/-4.3 years. There was a significant increase in the crude
      diabetes incidence rate with decreasing adolescent height percentile, from 4.23
      cases/104 person-years in the <10th percentile group to 2.44 cases/104 person
      years in the 75th<= percentile group. These results persisted when clinical and
      biochemical diabetes risk factors were included in multivariable models. Compared
      to the 75th<= percentile group, height below the 10th percentile was associated
      with a hazard ratio (HR) of 1.64 (95%CI 1.09-2.46, p = 0.017) for incident
      diabetes after adjustment for age, body mass index (BMI), fasting plasma glucose,
      HDL-cholesterol and triglyceride levels, white blood cells count, socioeconomic
      status, country of origin, family history of diabetes, sleep quality and physical
      activity. At age 30 years, each 1-cm decrement in adult height was associated
      with a 2.5% increase in diabetes adjusted risk (HR 1.025, 95%CI 1.01-1.04, p =
      0.001). CONCLUSIONS: Shorter height at late adolescence or young adulthood was
      associated with an increased risk of incident diabetes among young men,
      independent of BMI and other diabetes risk factors.

PMID- 26305681
TI  - Metal-induced malformations in early Palaeozoic plankton are harbingers of mass
      extinction.
AB  - Glacial episodes have been linked to Ordovician-Silurian extinction events, but
      cooling itself may not be solely responsible for these extinctions. Teratological
      (malformed) assemblages of fossil plankton that correlate precisely with the
      extinction events can help identify alternate drivers of extinction. Here we show
      that metal poisoning may have caused these aberrant morphologies during a late
      Silurian (Pridoli) event. Malformations coincide with a dramatic increase of
      metals (Fe, Mo, Pb, Mn and As) in the fossils and their host rocks. Metallic
      toxins are known to cause a teratological response in modern organisms, which is
      now routinely used as a proxy to assess oceanic metal contamination. Similarly,
      our study identifies metal-induced teratology as a deep-time, palaeobiological
      monitor of palaeo-ocean chemistry. The redox-sensitive character of enriched
      metals supports emerging 'oceanic anoxic event' models. Our data suggest that
      spreading anoxia and redox cycling of harmful metals was a contributing kill
      mechanism during these devastating Ordovician-Silurian palaeobiological events. 

PMID- 26305682
TI  - Composition and Diversity of the Fecal Microbiome and Inferred Fecal Metagenome
      Does Not Predict Subsequent Pneumonia Caused by Rhodococcus equi in Foals.
AB  - In equids, susceptibility to disease caused by Rhodococcus equi occurs almost
      exclusively in foals. This distribution might be attributable to the age
      dependent maturation of immunity following birth undergone by mammalian neonates
      that renders them especially susceptible to infectious diseases. Expansion and
      diversification of the neonatal microbiome contribute to development of immunity
      in the gut. Moreover, diminished diversity of the gastrointestinal microbiome has
      been associated with risk of infections and immune dysregulation. We thus
      hypothesized that varying composition or reduced diversity of the intestinal
      microbiome of neonatal foals would contribute to increased susceptibility of
      their developing R. equi pneumonia. The composition and diversity indices of the
      fecal microbiota at 3 and 5 weeks of age were compared among 3 groups of foals:
      1) foals that subsequently developed R. equi pneumonia after sampling; 2) foals
      that subsequently developed ultrasonographic evidence of pulmonary abscess
      formation or consolidation but not clinical signs (subclinical group); and, 3)
      foals that developed neither clinical signs nor ultrasonographic evidence of
      pulmonary abscess formation or consolidation. No significant differences were
      found among groups at either sampling time, indicating absence of evidence of an
      influence of composition or diversity of the fecal microbiome, or predicted fecal
      metagenome, on susceptibility to subsequent R. equi pneumonia. A marked and
      significant difference identified between a relatively short interval of time
      appeared to reflect ongoing adaptation to transition from a milk diet to a diet
      including available forage (including hay) and access to concentrate fed to the
      mare. 

PMID- 26305683
TI  - Augmentation Mastopexy with Implant and Autologous Tissue for Correction of
      Moderate/Severe Ptosis.
AB  - PURPOSE: Breast augmentation combined with mastopexy is associated with a
      significantly higher complication rate than augmentation alone. The combination
      of mastopexy and breast implants has revealed a moderate recurrence of breast
      ptosis in many patients particularly with use of medium to large implants. Ptosis
      is the "bottoming out" of the breast tissue with loss of the desired roundness,
      due to the ptosis of the breast implant and the mammary tissue. In this study, we
      hypothesize the need for careful planning and careful preoperative surgical
      execution to minimize this complication. PATIENTS AND METHODS: Between January
      2007 and July 2011, augmentation mastopexy with implant and autologous tissue
      ("double implant") was performed for 25 patients with grade III mammary ptosis.
      All patients underwent inverted-T mastopexy with supramuscular moderately
      cohesive gel breast implant using an inferior-based flap of de-epitelialized
      dermoglandular tissue and a superior-based nipple-areola complex pedicle.
      RESULTS: An inferior-based flap of deepithelialized dermoglandular tissue was
      used to stabilize the implant and is projection. Breast lifting was performed
      through a strong anchorage to fascia and to muscle of second intercostal space,
      improving the profile of the breast. Results were analyzed, no breast ptosis
      recurrence was noted at 30-month follow-up. CONCLUSIONS: Our technique presents
      the challenge of determining the amount of excess skin to be removed after
      implantation to create symmetry and provide for skin tightening without
      compromising tissue vascularization.

PMID- 26305685
TI  - Evaluation of Index of Cardio-Electrophysiological Balance (iCEB) as a New
      Biomarker for the Identification of Patients at Increased Arrhythmic Risk.
AB  - BACKGROUND: Recently a new risk marker for drug-induced arrhythmias called index
      of cardio-electrophysiological balance (iCEB), measured as QT interval divided by
      QRS duration, was evaluated in an animal model. It was hypothesized that iCEB is
      equivalent to the cardiac wavelength lambda (lambda = effective refractory period
      (ERP) x conduction velocity) and that an increased or decreased value of iCEB
      would potentially predict an increased susceptibility to TdP or non-TdP mediated
      VT/VF, respectively. METHODS: First, the correlation between QT interval and ERP
      was evaluated by invasively measuring ERP during a ventricular stimulation
      protocol in humans (N = 40). Then the effect of administration of sotalol and
      flecainide on iCEB was measured in 40 patients with supraventricular
      tachycardias. Finally iCEB was assessed in carriers of a long QT syndrome (LQTS,
      N = 70) or Brugada syndrome (BrS, N = 57) mutation and compared them with
      genotype negative family members (N = 65). RESULTS: The correlation between QT
      interval and ERP was established (Pearson R(2) = 0.25) which suggests that
      iCEB~ERPxCV~QT/QRS. Sotalol administration increased iCEB (+ 0.23; P = 0.01),
      while it decreased with the administration of flecainide (-0.21, P = 0.03). In
      the LQTS group iCEB was increased (5.22 +/- 0.93, P < 0.0001) compared to
      genotype negative family members (4.24 +/- 0.5), while it was decreased in the
      BrS group (3.52 +/- 0.43, P < 0.0001). CONCLUSIONS: Our data suggest that iCEB
      (QT/QRS) is a simple but effective ECG surrogate of cardiac wavelength. iCEB is
      increased in situations that predispose to TdP and is decreased in situations
      that predispose to non-TdP mediated VT/VF. Therefore, iCEB might serve as a
      noninvasive and readily measurable marker to detect increased arrhythmic risk.

PMID- 26305684
TI  - Irisin Controls Growth, Intracellular Ca2+ Signals, and Mitochondrial
      Thermogenesis in Cardiomyoblasts.
AB  - Exercise offers short-term and long-term health benefits, including an increased
      metabolic rate and energy expenditure in myocardium. The newly-discovered
      exercise-induced myokine, irisin, stimulates conversion of white into brown
      adipocytes as well as increased mitochondrial biogenesis and energy expenditure.
      Remarkably, irisin is highly expressed in myocardium, but its physiological
      effects in the heart are unknown. The objective of this work is to investigate
      irisin's potential multifaceted effects on cardiomyoblasts and myocardium. For
      this purpose, H9C2 cells were treated with recombinant irisin produced in yeast
      cells (r-irisin) and in HEK293 cells (hr-irisin) for examining its effects on
      cell proliferation by MTT [3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide] assay and on gene transcription profiles by qRT-PCR. R-irisin and hr
      irisin both inhibited cell proliferation and activated genes related to
      cardiomyocyte metabolic function and differentiation, including myocardin,
      follistatin, smooth muscle actin, and nuclear respiratory factor-1. Signal
      transduction pathways affected by r-irisin in H9C2 cells and C57BL/6 mice were
      examined by detecting phosphorylation of PI3K-AKT, p38, ERK or STAT3. We also
      measured intracellular Ca2+ signaling and mitochondrial thermogenesis and energy
      expenditure in r-irisin-treated H9C2 cells. The results showed that r-irisin, in
      a certain concentration rage, could activate PI3K-AKT and intracellular Ca2+
      signaling and increase cellular oxygen consumption in H9C2 cells. Our study also
      suggests the existence of irisin-specific receptor on the membrane of H9C2 cells.
      In conclusion, irisin in a certain concentration rage increased myocardial cell
      metabolism, inhibited cell proliferation and promoted cell differentiation. These
      effects might be mediated through PI3K-AKT and Ca2+ signaling, which are known to
      activate expression of exercise-related genes such as follistatin and myocardin.
      This work supports the value of exercise, which promotes irisin release. 

PMID- 26305686
TI  - Correction: Evidence for a Role of the Transcriptional Regulator Maid in
      Tumorigenesis and Aging.

PMID- 26305688
TI  - Evaluation of the main coagulation tests in the presence of hemolysis in healthy
      subjects and patients on oral anticoagulant therapy.
AB  - INTRODUCTION: Our study was designed to evaluate, on healthy subjects and
      patients on oral anticoagulant therapy vitamin K antagonist (OAT-vka), the
      possible interference caused by hemolysis on the main coagulation tests. METHODS:
      To obtain hemolyzed samples, two methods were used: heat shock and mechanical
      system. The coagulation tests on hemolyzed samples were performed employing
      optical automated analyser BCSxp (Siemens Healthcare((r))). Moreover, the
      prothrombin time (PT) and activated partial thromboplastin time (aPTT) tests were
      also carried out manually using an electromechanical device (KC4 - Amelung).
      RESULTS: The PT test, on healthy subjects, in case of moderate hemolysis can be
      performed without significant interference on automatic instrument. On manual
      instrument, the PT test can be performed even in case of marked hemolysis. For
      patients on OAT-vka, the PT test in case of marked hemolysis can be performed
      both on automatic and manual instrument. For the aPTT test, it can be carried out
      manually, because also in case of marked hemolysis a statistically significant
      difference was not observed. For the fibrinogen test, a dramatic concentration
      decrease was already clear for weak hemolysis. A decreased function on
      antithrombin test was statistically significant for mild-moderate hemolysis. The
      D-dimer test showed increased values for mild hemolysis. CONCLUSIONS: The
      rejection of hemolyzed sample and/or the request of a second sample are not
      always the proper attitudes to take for performing clotting tests. The rational
      management of the hemolyzed samples decreases the employment of both nursing and
      technical staff significantly, the turnaround time and, consequently, does not
      lead to additional costs for each patient involved.

PMID- 26305687
TI  - Fungal endophyte infection of ryegrass reprograms host metabolism and alters
      development.
AB  - Beneficial associations between plants and microbes play an important role in
      both natural and agricultural ecosystems. For example, associations between fungi
      of the genus Epichloe, and cool-season grasses are known for their ability to
      increase resistance to insect pests, fungal pathogens and drought. However,
      little is known about the molecular changes induced by endophyte infection. To
      study the impact of endophyte infection, we compared the expression profiles,
      based on RNA sequencing, of perennial ryegrass infected with Epichloe festucae
      with noninfected plants. We show that infection causes dramatic changes in the
      expression of over one third of host genes. This is in stark contrast to
      mycorrhizal associations, where substantially fewer changes in host gene
      expression are observed, and is more similar to pathogenic interactions. We
      reveal that endophyte infection triggers reprogramming of host metabolism,
      favouring secondary metabolism at a cost to primary metabolism. Infection also
      induces changes in host development, particularly trichome formation and cell
      wall biogenesis. Importantly, this work sheds light on the mechanisms underlying
      enhanced resistance to drought and super-infection by fungal pathogens provided
      by fungal endophyte infection. Finally, our study reveals that not all beneficial
      plant-microbe associations behave the same in terms of their effects on the host.

PMID- 26305689
TI  - Reduced Crossover Interference and Increased ZMM-Independent Recombination in the
      Absence of Tel1/ATM.
AB  - Meiotic recombination involves the repair of double-strand break (DSB) precursors
      as crossovers (COs) or noncrossovers (NCOs). The proper number and distribution
      of COs is critical for successful chromosome segregation and formation of viable
      gametes. In budding yeast the majority of COs occurs through a pathway dependent
      on the ZMM proteins (Zip2-Zip3-Zip4-Spo16, Msh4-Msh5, Mer3), which form foci at
      CO-committed sites. Here we show that the DNA-damage-response kinase Tel1/ATM
      limits ZMM-independent recombination. By whole-genome mapping of recombination
      products, we find that lack of Tel1 results in higher recombination and reduced
      CO interference. Yet the number of Zip3 foci in tel1Delta cells is similar to
      wild type, and these foci show normal interference. Analysis of recombination in
      a tel1Delta zip3Delta double mutant indicates that COs are less dependent on Zip3
      in the absence of Tel1. Together these results reveal that in the absence of
      Tel1, a significant proportion of COs occurs through a non-ZMM-dependent pathway,
      contributing to a CO landscape with poor interference. We also see a significant
      change in the distribution of all detectable recombination products in the
      absence of Tel1, Sgs1, Zip3, or Msh4, providing evidence for altered DSB
      distribution. These results support the previous finding that DSB interference
      depends on Tel1, and further suggest an additional level of DSB interference
      created through local repression of DSBs around CO-designated sites. 

PMID- 26305690
TI  - Chitosan as a Biomaterial: Influence of Degree of Deacetylation on Its
      Physiochemical, Material and Biological Properties.
AB  - Chitosan is a biomaterial with a range of current and potential biomedical
      applications. Manipulation of chitosan degree of deacetylation (DDA) to achieve
      specific properties appears feasible, but studies investigating its influence on
      properties are often contradictory. With a view to the potential of chitosan in
      the regeneration of nerve tissue, the influence of DDA on the growth and health
      of olfactory ensheathing cells (OECs) was investigated. There was a linear
      increase in OEC proliferation as the DDA increased from 72 to 85%. This
      correlated with linear increases in average surface roughness (0.62 to 0.78 MUm)
      and crystallinity (4.3 to 10.1%) of the chitosan films. Mitochondrial activity
      and membrane integrity of OECs was significantly different for OECs cultivated on
      chitosan with DDAs below 75%, while those on films with DDAs up to 85% were
      similar to cells in asynchronous growth. Apoptotic indices and cell cycle
      analysis also suggested that chitosan films with DDAs below 75% were
      cytocompatible but induced cellular stress, while OECs grown on films fabricated
      from chitosan with DDAs above 75% showed no significant differences compared to
      those in asynchronous growth. Tensile strength and elongation to break varied
      with DDA from 32.3 to 45.3 MPa and 3.6 to 7.1% respectively. DDA had no
      significant influence on abiotic and biotic degradation profiles of the chitosan
      films which showed approximately 8 and 20% weight loss respectively. Finally,
      perceived patterns in property changes are subject to change based on potential
      variations in DDA analysis. NMR examination of the chitosan samples here revealed
      significant differences depending upon which peaks were selected for integration;
      6 to 13% in DDA values within individual samples. Furthermore, differences
      between DDA values determined here and those reported by the commercial suppliers
      were significant and this may also be a source of concern when selecting
      commercial chitosans for biomaterial research. 

PMID- 26305691
TI  - Proteomics-Based Characterization of the Humoral Immune Response in
      Sporotrichosis: Toward Discovery of Potential Diagnostic and Vaccine Antigens.
AB  - BACKGROUND: Sporothrix schenckii and associated species are agents of human and
      animal sporotrichosis that cause large sapronoses and zoonoses worldwide.
      Epidemiological surveillance has highlighted an overwhelming occurrence of the
      highly pathogenic fungus Sporothrix brasiliensis during feline outbreaks, leading
      to massive transmissions to humans. Early diagnosis of feline sporotrichosis by
      demonstrating the presence of a surrogate marker of infection can have a key role
      for selecting appropriate disease control measures and minimizing zoonotic
      transmission to humans. METHODOLOGY: We explored the presence and diversity of
      serum antibodies (IgG) specific against Sporothrix antigens in cats with
      sporotrichosis and evaluated the utility of these antibodies for serodiagnosis.
      Antigen profiling included protein extracts from the closest known relatives S.
      brasiliensis and S. schenckii. Enzyme-linked immunosorbent assays and
      immunoblotting enabled us to characterize the major antigens of feline
      sporotrichosis from sera from cats with sporotrichosis (n = 49), healthy cats (n
      = 19), and cats with other diseases (n = 20). PRINCIPAL FINDINGS: Enzyme-linked
      immunosorbent assay-based quantitation of anti-Sporothrix IgG exhibited high
      sensitivity and specificity in cats with sporotrichosis (area under the curve,
      1.0; 95% confidence interval, 0.94-1; P<0.0001) versus controls. The two sets of
      Sporothrix antigens were remarkably cross-reactive, supporting the hypothesis
      that antigenic epitopes may be conserved among closely related agents. One
      dimensional immunoblotting indicated that 3-carboxymuconate cyclase (a 60-kDa
      protein in S. brasiliensis and a 70-kDa protein in S. schenckii) is the
      immunodominant antigen in feline sporotrichosis. Two-dimensional immunoblotting
      revealed six IgG-reactive isoforms of gp60 in the S. brasiliensis proteome,
      similar to the humoral response found in human sporotrichosis. CONCLUSIONS: A
      convergent IgG-response in various hosts (mice, cats, and humans) has important
      implications for our understanding of the coevolution of Sporothrix and its warm
      blooded hosts. We propose that 3-carboxymuconate cyclase has potential for the
      serological diagnosis of sporotrichosis and as target for the development of an
      effective multi-species vaccine against sporotrichosis in animals and humans.

PMID- 26305693
TI  - The Prognostic Value of Forkhead Box P3 Expression in Operable Breast Cancer: A
      Large-Scale Meta-Analysis.
AB  - BACKGROUND: Recent studies have shown that the forkhead box P3 (FOXP3) protein
      has a prognostic role in breast cancer. However, these results are controversial.
      Therefore, the aim of this meta-analysis was to clarify the prognostic role of
      FOXP3 expression in operable breast cancer cases. METHODS: Eligible studies
      describing the use of FOXP3 as a prognostic factor for operable breast cancer
      cases were identified. Clinicopathological features, disease-free survival (DFS),
      and overall survival (OS) data were collected from these studies and were
      analyzed using Stata software. RESULTS: A total of 16 articles containing data
      from 13,217 breast cancer patients met the inclusion criteria established for
      this study. The subsequent meta-analysis that was performed showed that high
      levels of FOXP3 are not significantly associated with DFS and OS with significant
      heterogeneity. An additional subgroup analysis demonstrated that intratumoral
      FOXP3+ regulatory T cells (Tregs) were positively correlated with adverse
      clinicopathological parameters, yet they did not show an association with DFS or
      OS. For tumor cells, the pooled results revealed that FOXP3 is significantly
      associated with DFS (HR: 2.55, 95% CI: 1.23-5.30) but is not associated with
      clinicopathological parameters or OS. We also observed a significant correlation
      between FOXP3 expression and survival in the estrogen receptor-positive (ER)+
      subgroup (HR: 1.83, 95% CI: 1.36-2.47 for DFS, HR: 1.87, 95% CI 1.28-2.73 for
      OS), in the Asian region (HR: 1.98, 95% CI: 1.56-2.50 for DFS, HR: 1.93, 95% CI:
      1.12-3.35 for OS) and using the median as the FOXP3-positive cut-off value (HR:
      1.94, 95% CI: 1.57-2.39 for DFS, HR: 2.06; 95% CI: 1.36-3.11 for OS). CONCLUSION:
      This meta-analysis indicates that a prognostic role for FOXP3 expression in
      operable breast cancer cases depends on the FOXP3-positive region, ER status,
      geographic region and the FOXP3-positive cut-off value.

PMID- 26305692
TI  - Development of a Novel Model for the Assessment of Dead-Space Management in Soft
      Tissue.
AB  - Following extensive surgical debridement in the treatment of infection, a "dead
      space" can result following surgical closure that can fill with hematoma, an
      environment conducive to bacterial growth. The eradication of dead space is
      essential in order to prevent recurrent infection. This study describes a novel
      small animal model to investigate dead-space management in muscle tissue. Two
      absorbable test materials were implanted in each animal; beads of calcium sulfate
      alone, and beads loaded with vancomycin and tobramycin. In-life blood samples and
      radiographs were taken from each animal following implantation. Animals were
      sacrificed at 1, 7, 21, 42, and 63 days post-operatively (n = 4), and implant
      sites were analysed by micro-computed tomography, histology and
      immunohistochemistry. Complete resorption was confirmed radiographically at 3
      weeks post-implantation. Histologically, the host tissue response to both
      materials was identical, and subsequent healing at the implant sites was observed
      with no dead space remaining. Vancomycin was not detected in blood serum.
      However, peak tobramycin levels were detected in all animals at 6 hours post
      implantation with no detectable levels in any animals at 72 hours post
      implantation. Serological inflammatory cytokine expression for IL-6, TNF-alpha
      and IL-1beta indicated no unusual inflammatory response to the implanted
      materials or surgical procedure. The model was found to be convenient and
      effective for the assessment of implant materials for management of dead space in
      muscle tissue. The two materials tested were effective in resolving the
      surgically created dead space, and did not elicit any unexpected adverse host
      response. 

PMID- 26305695
TI  - Two new triterpenoids from the seeds of blackberry (Rubus fructicosus).
AB  - Two new ursane-type triterpenoids (1, 2) attached to isopropylidenedioxy group
      were isolated from the seeds of blackberry (Rubus fructicosus L., Rosaceae) along
      with two known ursane-type triterpenoids, 2,3-O-isopropylidenyl
      2alpha,3alpha,19alpha-trihydroxyurs-12-en-28-oic acid (3) and 1beta
      hydroxyeuscaphic acid (4). The chemical structures of 1 and 2 were determined to
      be 2,3-O-isopropylidene-1beta,2beta,3beta,19alpha-tetrahydroxyurs-12-en-28-oic
      acid and 1,2-O-isopropylidene-1beta,2alpha,3alpha,19alpha-tetrahydroxyurs-12-en
      28-oic acid, respectively, based on spectroscopic data. Additionally, their
      cytotoxic activity towards HL-60 human leukaemia cells was evaluated. Among them,
      3 demonstrated a clear cytotoxic activity with 72.8 MUM of IC50 value.

PMID- 26305694
TI  - Auditory Spatial Discrimination and the Mismatch Negativity Response in Hearing
      Impaired Individuals.
AB  - The aims of the present study were to investigate the ability of hearing-impaired
      (HI) individuals with different binaural hearing conditions to discriminate
      spatial auditory-sources at the midline and lateral positions, and to explore the
      possible central processing mechanisms by measuring the minimal audible angle
      (MAA) and mismatch negativity (MMN) response. To measure MAA at the left/right 0
      degrees , 45 degrees  and 90 degrees  positions, 12 normal-hearing (NH)
      participants and 36 patients with sensorineural hearing loss, which included 12
      patients with symmetrical hearing loss (SHL) and 24 patients with asymmetrical
      hearing loss (AHL) [12 with unilateral hearing loss on the left (UHLL) and 12
      with unilateral hearing loss on the right (UHLR)] were recruited. In addition,
      128-electrode electroencephalography was used to record the MMN response in a
      separate group of 60 patients (20 UHLL, 20 UHLR and 20 SHL patients) and 20 NH
      participants. The results showed MAA thresholds of the NH participants to be
      significantly lower than the HI participants. Also, a significantly smaller MAA
      threshold was obtained at the midline position than at the lateral position in
      both NH and SHL groups. However, in the AHL group, MAA threshold for the 90
      degrees  position on the affected side was significantly smaller than the MMA
      thresholds obtained at other positions. Significantly reduced amplitudes and
      prolonged latencies of the MMN were found in the HI groups compared to the NH
      group. In addition, contralateral activation was found in the UHL group for
      sounds emanating from the 90 degrees  position on the affected side and in the NH
      group. These findings suggest that the abilities of spatial discrimination at the
      midline and lateral positions vary significantly in different hearing conditions.
      A reduced MMN amplitude and prolonged latency together with bilaterally
      symmetrical cortical activations over the auditory hemispheres indicate possible
      cortical compensatory changes associated with poor behavioral spatial
      discrimination in individuals with HI. 

PMID- 26305696
TI  - Solvothermal Synthesis of Lateral Heterojunction Sb2Te3/Bi2Te3 Nanoplates.
AB  - A lateral heterojunction of topological insulator Sb2Te3/Bi2Te3 was successfully
      synthesized using a two-step solvothermal method. The two crystalline components
      were separated well by a sharp lattice-matched interface when the optimized
      procedure was used. Inspecting the heterojunction using high-resolution
      transmission electron microscopy showed that epitaxial growth occurred along the
      horizontal plane. The semiconducting temperature-resistance curve and
      crossjunction rectification were observed, which reveal a staggered-gap lateral
      heterojunction with a small junction voltage. Quantum correction from the weak
      antilocalization reveals the well-maintained transport of the topological surface
      state. This is appealing for a platform for spin filters and one-dimensional
      topological interface states. 

PMID- 26305697
TI  - Stigma and Human Rights Abuses against People Who Inject Drugs in Russia--A
      Qualitative Investigation to Inform Policy and Public Health Strategies.
AB  - INTRODUCTION: Drug policing practices in the Russian Federation (Russia) are
      often punitive and have been shown to be associated with HIV risk behaviors among
      people who inject drugs (PWID). Less is known about strategies to address the
      problem in that setting, where substance use stigma is highly persistent. A
      better understanding of forms, causes and consequences of drug policing in Russia
      could inform drug policy in a context of substantial policy resistance. This
      qualitative study's goal is to characterize the phenomenon of police involvement
      with Russian PWID and to explore strategies for drug policing in the Russian
      country context. METHODS: Using a semi-structured interview guide, we collected
      data from a purposive sample of 23 key informants including PWID, police
      officers, and experts from civil society and international organizations in
      Russia. We used a thematic analysis approach to inductively generate new insight
      into the phenomenon of police involvement and potential strategies to address it.
      RESULTS: Policing practices involving PWID include unjustified arrests, planting
      of false evidence and extrajudicial syringe confiscations, and often constitute
      human rights violations. Russian PWID personally experienced police violence as
      ubiquitous, taking on various forms such as beating, unjustified arrests, verbal
      harassment, and coercion. The persistent societal stigma dehumanizes PWID, and
      such stigmatization facilitates police abuse. To address stigma and overcome the
      PWID-police adversity, study participants suggested fostering a mutual
      understanding between the police and public health sectors. CONCLUSIONS:
      Participants describe substantial human rights violations as part of policing
      illicit drug use in Russia. Police should include principles of effective
      prevention of substance use and HIV risk reduction in their trainings. Alignment
      of public safety and public health goals could address drug use-related risks and
      HIV prevention among key populations in Russia.

PMID- 26305698
TI  - Factors That Influence the Extensional Rheological Property of Saliva.
AB  - The spinnbarkeit of saliva reflects the ability of saliva to adhere to surfaces
      within the mouth, thereby serving as a protective role and aiding in lubrication.
      Therefore, alterations in the extensional rheology of saliva may result in the
      loss in adhesiveness or the ability to bind onto surfaces. Mucin glycoproteins
      and their structures are known to be important factors for the extensional
      rheological properties of saliva. The conformation of mucin depends on factors
      such as pH and ionic strength. Chewing is one of the main stimuli for salivary
      secretion but creates significant sheer stress on the salivary film which could
      influence mouthfeel perceptions. The current study investigates the possible
      factors which affect the extensional rheological properties of saliva by
      comparing submandibular/sublingual saliva with different oral stimuli within the
      same group of subjects. Unstimulated and stimulated saliva (chew, smell and
      taste) salivas were collected primarily from submandibular/sublingual glands. The
      saliva samples were measured for Spinnbarkeit followed by the measuring mucin,
      total protein, total calcium and bicarbonate concentrations. The results
      indicated correlations between rheological properties and mucin/ion
      concentrations. However, chewing stimulated submandibular/sublingual saliva is
      shown to have significantly lower Spinnbarkeit, but factors such as mucin,
      protein and calcium concentrations did not account for this variation. Analysis
      of the concentration of bicarbonate and pH appears to suggest that it has a
      prominent effect on extensional rheology of saliva. 

PMID- 26305699
TI  - Correction: CDK8-Cyclin C Mediates Nutritional Regulation of Developmental
      Transitions through the Ecdysone Receptor in Drosophila.

PMID- 26305700
TI  - Anesthesia and Monitoring in Small Laboratory Mammals Used in Anesthesiology,
      Respiratory and Critical Care Research: A Systematic Review on the Current
      Reporting in Top-10 Impact Factor Ranked Journals.
AB  - RATIONALE: This study aimed to investigate the quality of reporting of anesthesia
      and euthanasia in experimental studies in small laboratory mammals published in
      the top ten impact factor journals. METHODS: A descriptive systematic review was
      conducted and data was abstracted from the ten highest ranked journals with
      respect to impact factor in the categories 'Anesthesiology', 'Critical Care
      Medicine' and 'Respiratory System' as defined by the 2012 Journal Citation
      Reports. Inclusion criteria according to PICOS criteria were as follows: 1)
      population: small laboratory mammals; 2) intervention: any form of anesthesia
      and/or euthanasia; 3) comparison: not specified; 4) primary outcome: type of
      anesthesia, anesthetic agents and type of euthanasia; secondary outcome: animal
      characteristics, monitoring, mechanical ventilation, fluid management,
      postoperative pain therapy, animal care approval, sample size calculation and
      performed interventions; 5) study: experimental studies. Anesthesia, euthanasia,
      and monitoring were analyzed per performed intervention in each article. RESULTS:
      The search yielded 845 articles with 1,041 interventions of interest. Throughout
      the manuscripts we found poor quality and frequency of reporting with respect to
      completeness of data on animal characteristics as well as euthanasia, while
      anesthesia (732/1041, 70.3%) and interventions without survival (970/1041, 93.2%)
      per se were frequently reported. Premedication and neuromuscular blocking agents
      were reported in 169/732 (23.1%) and 38/732 (5.2%) interventions, respectively.
      Frequency of reporting of analgesia during (117/610, 19.1%) and after painful
      procedures (38/364, 10.4%) was low. Euthanasia practice was reported as
      anesthesia (348/501, 69%), transcardial perfusion (37/501, 8%), carbon dioxide
      (26/501, 6%), decapitation (22/501, 5%), exsanguination (23/501, 5%), other
      (25/501, 5%) and not specified (20/501, 4%, respectively. CONCLUSIONS: The
      present systematic review revealed insufficient reporting of anesthesia and
      euthanasia methods throughout experimental studies in small laboratory mammals.
      Specific guidelines for anesthesia and euthanasia regimens should be considered
      to achieve comparability, quality of animal experiments and animal welfare. These
      measures are of special interest when translating experimental findings to future
      clinical applications.

PMID- 26305703
TI  - Influence of self-assembling redox mediators on charge transfer at hydrophobic
      electrodes.
AB  - We report an investigation of the influence of reversible self-assembly of
      amphiphilic redox-mediators on interfacial charge transfer at chemically
      functionalized electrodes. Specifically, we employed (11-ferrocenylundecyl)
      trimethylammonium bromide (FTMA) as a model self-assembling redox mediator and
      alkanethiol-modified gold films as hydrophobic electrodes. By performing cyclic
      voltammetry (CV, 10 mV/s) in aqueous solutions containing FTMA above its critical
      micellar concentration (CMC), we measured anodic (Ia) and cathodic (Ic) peak
      current densities of 18 +/- 3 and 1.1 +/- 0.1 MUA/cm(2), respectively, revealing
      substantial current rectification (Ia/Ic= 17) at the hydrophobic electrodes. In
      contrast, hydroxymethyl ferrocene (a non-self-assembling redox mediator) at
      hydrophobic electrodes and FTMA at bare gold electrodes, yielded relatively low
      levels of rectification (Ia/Ic= 1.7 and 2.3, respectively). Scan-rate-dependent
      measurements revealed Ia of FTMA to arise largely from the diffusion of FTMA from
      bulk solution to the hydrophobic electrode whereas Ic was dominated by adsorbed
      FTMA, leading to the proposal that current rectification observed with FTMA is
      mediated by interfacial assemblies of reduced FTMA that block access of oxidized
      FTMA to the hydrophobic electrode. Support for this proposal was obtained by
      using atomic force microscopy and quartz crystal microbalance measurements to
      confirm the existence of interfacial assemblies of reduced FTMA (1.56 +/- 0.2
      molecules/nm(2)). Additional characterization of a mixed surfactant system
      containing FTMA and dodecyltrimethylammonium bromide (DTAB) revealed that
      interfacial assemblies of DTAB also block access of oxidized FTMA to hydrophobic
      electrodes; this system exhibited Ia/Ic > 80. These results and others reported
      in this paper suggest that current rectification occurs in this system because
      oxidized FTMA does not mix with interfacial assemblies of reduced FTMA or DTAB
      formed at hydrophobic electrodes. More broadly, these results show that self
      assembling redox mediators, when combined with chemically functionalized
      electrodes, offer the basis of new principles for controlling charge transfer at
      electrode/solution interfaces. 

PMID- 26305702
TI  - On the Origin and Evolution of the Extant System of B Chromosomes in Oryzomyini
      Radiation (Rodentia, Sigmodontinae).
AB  - Heterogeneous supernumerary chromosomes (Bs) are recognized in the oryzomyines
      Holochilus brasiliensis, Nectomys rattus, N. squamipes, Oligoryzomys flavescens
      and Sooretamys angouya, representing about 10% of all known B-containing rodent
      species. They provide an outstanding model for understanding the origin,
      evolution and diversity of Bs in a phylogenetic context. Therefore, whole
      chromosome-specific probes were generated from flow-sorted Holochilus
      brasiliensis (HBR) autosomes 11 and 25+26 and chromosomes X, Y and Bs.
      Hybridizations were performed on male metaphases of 15 Oryzomyini species of
      which 3 are B-containing species. The results reveal that among the species
      sampled, 12 of them, belonging to a monophyletic Oryzomiyini subclade, are
      positive for an anonymous Oryzomyini shared heterochromatic region (OSHR) on both
      sex chromosomes. The OSHR is also present on Bs of Holochilus brasiliensis,
      Nectomys rattus and N. squamipes but not on Bs of O. flavescens and S. angouya.
      Two distinct additional OSHR/autosome associations are observed on S. angouya.
      The three species that are OSHR negative belong to an outgroup. Molecular dating
      suggests that the OSHR originated between 7.8 and 3 Mya on ancestral sex
      chromosomes. A tentative explanation for the OSHR-positive nature of B regions in
      three species could be that transposable elements (TEs) from this specific sex
      chromosome region may have invaded existing B chromosomes. The presence of the
      OSHR on entire Xp and Yp adjacent to interstitial telomeric sequences at
      pericentromeric positions, as observed in Drymoreomys albimaculatus, show a
      similar organization as on B chromosomes in Nectomys squamipes. The diversity of
      the Oryzomyini Bs in number, size, morphology and genetic content may be
      explained by the independent origin of B chromosomes in different subgroups of
      species, with Bs in Holochilus brasiliensis, Nectomys squamipes and N. rattus
      sharing the OSHR with sex chromosomes, and those in Oligoryzomys flavescens and
      Sooretamys angouya lacking OSHR in Bs. The species-specific pattern of Bs is
      probably a consequence of their independent evolutionary origin. 

PMID- 26305704
TI  - Hormones and Cancer--Looking Forward.

PMID- 26305705
TI  - Detection of Ultra-Rare Mitochondrial Mutations in Breast Stem Cells by Duplex
      Sequencing.
AB  - Long-lived adult stem cells could accumulate non-repaired DNA damage or mutations
      that increase the risk of tumor formation. To date, studies on mutations in stem
      cells have concentrated on clonal (homoplasmic) mutations and have not focused on
      rarely occurring stochastic mutations that may accumulate during stem cell
      dormancy. A major challenge in investigating these rare mutations is that
      conventional next generation sequencing (NGS) methods have high error rates. We
      have established a new method termed Duplex Sequencing (DS), which detects
      mutations with unprecedented accuracy. We present a comprehensive analysis of
      mitochondrial DNA mutations in human breast normal stem cells and non-stem cells
      using DS. The vast majority of mutations occur at low frequency and are not
      detectable by NGS. The most prevalent point mutation types are the C>T/G>A and
      A>G/T>C transitions. The mutations exhibit a strand bias with higher prevalence
      of G>A, T>C, and A>C mutations on the light strand of the mitochondrial genome.
      The overall rare mutation frequency is significantly lower in stem cells than in
      the corresponding non-stem cells. We have identified common and unique non
      homoplasmic mutations between non-stem and stem cells that include new mutations
      which have not been reported previously. Four mutations found within the MT-ND5
      gene (m.12684G>A, m.12705C>T, m.13095T>C, m.13105A>G) are present in all groups
      of stem and non-stem cells. Two mutations (m.8567T>C, m.10547C>G) are found only
      in non-stem cells. This first genome-wide analysis of mitochondrial DNA mutations
      may aid in characterizing human breast normal epithelial cells and serve as a
      reference for cancer stem cell mutation profiles. 

PMID- 26305707
TI  - Enhanced Visible Light-Induced Charge Separation and Charge Transport in Cu2O
      Based Photocathodes by Urea Treatment.
AB  - Carrier density, photocharge transfer kinetics, and charge transfer resistance of
      the anodized Cu-Cu2O-CuO photocathode were greatly improved using thermal
      treatment with urea. Time-correlated single-photon counting (TCSPC) results
      revealed the faster electron transfer kinetics from Cu2O to CuO in the urea
      treated Cu-Cu2O-CuO composite photoelectrodes. Preservation of the metallic
      copper component via the intermediate Cu3N during the treatment facilitated
      higher bulk conductance of the Cu-Cu2O-CuO photocathode for improved charge
      transport. Higher carrier density was also observed in the urea-treated
      photoelectrode, which was possibly attributed to the presence of nitrogen as a
      dopant. Furthermore, the compact outer layer of CuO protected the underlayer Cu2O
      from being in direct contact with the aqueous solution. This suppressed the
      photocorrosion of Cu2O and resulted in the higher photostability of the Cu-Cu2O
      CuO film. When these advantages were combined, the urea-treated Cu-Cu2O-CuO film
      showed a higher photocurrent of 2.2 mA/cm2 and improved stability versus that of
      the conventional Cu-Cu2O-CuO film (1.2 mA/cm2). To improve the charge transfer
      kinetics and carrier density, this paper provides a new strategy for synthesizing
      effective and stable Cu2O-based photoelectrodes by using urea treatment.

PMID- 26305706
TI  - Modeling hepatitis C virus transmission among people who inject drugs:
      Assumptions, limitations and future challenges.
AB  - The discovery of highly effective hepatitis C virus (HCV) treatments has led to
      discussion of elimination and intensified interest in models of HCV transmission.
      In developed settings, HCV disproportionally affects people who inject drugs
      (PWID), and models are typically used to provide an evidence base for the
      effectiveness of interventions such as needle and syringe programs, opioid
      substitution therapy and more recently treating PWID with new generation
      therapies to achieve specified reductions in prevalence and / or incidence. This
      manuscript reviews deterministic compartmental S-I, deterministic compartmental S
      I-S and network-based transmission models of HCV among PWID. We detail typical
      assumptions made when modeling injecting risk behavior, virus transmission,
      treatment and re-infection and how they correspond with available evidence and
      empirical data. 

PMID- 26305709
TI  - Lithium Di- and trimethyl dimolybdenum(II) complexes with Mo-Mo quadruple bonds
      and bridging methyl groups.
AB  - New dimolybdenum complexes of composition [Mo2{MU-Me}2Li(S)}(MU-X)(MU-N^N)2] (3a
      3c), where S = THF or Et2O and N^N represents a bidentate aminopyridinate or
      amidinate ligand that bridges the quadruply bonded molybdenum atoms, were
      prepared from the reaction of the appropriate [Mo2{MU-O2CMe}2(MU-N^N)2]
      precursors and LiMe. For complex 3a, X = MeCO2, while in 3b and 3c, X = Me.
      Solution NMR studies in C6D6 solvent support formulation of the complexes as
      contact ion pairs with weak agostic Mo-CH3...Li interactions, which were also
      evidenced by X-ray crystallography in the solid-state structures of the molecules
      of 3a and 3b. Samples of 3c enriched in (13)C (99%) at the metal-bonded methyl
      sites were also prepared and investigated by NMR spectroscopy employing C6D6 and
      THF-d8 solvents. Crystallization of 3c from toluene:tetrahydrofuran mixtures
      provided single crystals of the solvent separated ion pair complex [Li(THF)4]
      [Mo2(Me)2(MU-Me){MU-HC(NDipp)2}2] (4c), where Dipp stands for 2,6-iPr2C6H3. A
      computational analysis of the Mo2(MU-Me)2Li core of complexes 3a and 3b has been
      developed, which is consistent with a small but non-negligible electron-density
      sharing between the C and Li atoms of the mainly ionic CH3...Li interactions. 

PMID- 26305708
TI  - Targeted Inhibition of Snail Activity in Breast Cancer Cells by Using a Co(III) 
      Ebox Conjugate.
AB  - The transition from a non-invasive to an invasive phenotype is an essential step
      in tumor metastasis. The Snail family of transcription factors (TFs) is known to
      play a significant role in this transition. These TFs are zinc fingers that bind
      to the CAGGTG Ebox consensus sequence. Co(III) -Ebox is a cobalt(III) complex
      attached to an Ebox oligonucleotide that confers specificity towards Snail TFs.
      Co(III) -Ebox has been shown to inhibit Snail-mediated embryonic neural crest
      development in Xenopus laevis, but its efficacy in inhibiting Snail-induced
      cancer cell invasiveness has not been explored. Here, we describe the efficacy of
      Co(III) -Ebox in inhibiting the invasive aspects of heregulin-beta1(HRG)-treated
      breast cancer cells. Co(III) -Ebox was found to inhibit the capacity of Snail to
      repress target genes after HRG induction. Snail inhibition by Co(III) -Ebox
      reduced the invasive propensity of cells in 2D and 3D, thereby demonstrating
      promise in inhibiting metastasis. 

PMID- 26305710
TI  - QSAR analysis of nicotinamidic compounds and design of potential Bruton's
      tyrosine kinase (Btk) inhibitors.
AB  - Bruton's tyrosine kinase (Btk) is an important enzyme in B-lymphocyte development
      and differentiation. Furthermore, Btk expression is considered essential for the
      proliferation and survival of these cells. Btk inhibition has become an
      attractive strategy for treating autoimmune diseases, B-cell leukemia, and
      lymphomas. With the objective of proposing new candidates for Btk inhibitors, we
      applied receptor-dependent four-dimensional quantitative structure-activity
      relationship (QSAR) methodology to a series of 96 nicotinamide analogs useful as
      Btk modulators. The QSAR models were developed using 71 compounds, the training
      set, and externally validated using 25 compounds, the test set. The conformations
      obtained by molecular dynamics simulation were overlapped in a virtual three
      dimensional cubic box comprised of 2 and 5 A cells, according to the six trial
      alignments. The models were generated by combining genetic function approximation
      and partial least squares regression technique. The analyses suggest that Model
      1a yields the best results. The best equation shows [Formula: see text], r(2) =
      .743, RMSEC = .831, RMSECV = .879. Given the importance of the Tyr551, this
      residue could become a strategic target for the design of novel Btk inhibitors
      with improved potency. In addition, the good potency predicted for the proposed
      M2 compound indicates this compound as a potential Btk inhibitor candidate. 

PMID- 26305711
TI  - The self-harm inventory: A meta-analysis of its relationship to the personality
      diagnostic questionnaire-4 as a measure of borderline personality disorder.
AB  - OBJECTIVE: The purpose of the present study was to further examine the efficacy
      of the Self-Harm Inventory (SHI) as a proxy measure in diagnosing borderline
      personality disorder, with the comparison measure being the Personality
      Diagnostic Questionnaire-4 (PDQ-4). METHODS: We undertook a meta-analysis of data
      from our previous studies of psychiatric inpatients (N = 270) and internal
      medicine outpatients (N = 2587), all of whom completed both the SHI and the PDQ
      4. RESULTS: Scores on the SHI and PDQ-4 were strongly correlated, especially
      after correcting for attenuation due to measurement unreliability (0.78 in the
      compiled inpatient psychiatry sample and 0.83 in the compiled internal medicine
      sample). Moreover, the SHI demonstrated statistically significantly greater
      reliability coefficients relative to the PDQ-4. CONCLUSIONS: Based upon
      comparison with the PDQ-4, the SHI appears to be an efficacious proxy measure of
      borderline personality symptomatology in both psychiatric inpatient samples and
      primary care outpatient samples.

PMID- 26305713
TI  - A meta-analysis of HBsAg-positive rate among general Chinese populations aged 1-
      59 years.
AB  - BACKGROUND: The third nationwide hepatitis B virus (HBV) sero-epidemiological
      survey conducted in China in 2006 showed a hepatitis B surface antigen (HBsAg)
      positive rate of 7.18% and the number of carriers to be 93 million. To compensate
      for the lack of data on the national prevalence of hepatitis B from 2006 onwards,
      we performed a meta-analysis to investigate HBsAg-positive rates among the
      general Chinese population aged 1-59 years. METHODS: We systemically reviewed
      published studies (January 2007 to September 2013) from full-text databases such
      as VIP, Chinese National Knowledge Infrastructure, and PubMed and assessed HBsAg
      positive rates using a random effects regression model with comprehensive meta
      analysis software. RESULTS: After evaluation of the quality of the papers, 36
      were finally included, with a total sample size of 314 103 individuals. The meta
      analysis showed that the combined HBsAg-positive rate was 6.1% (95% confidence
      interval (CI), 5.4-6.8%) among general Chinese populations aged 1-59, with a
      higher HBsAg-positive rate in males (6.6%; 95% CI, 5.7-7.7%) than in females
      (5.1%; 95% CI, 4.4-5.9%). Our data also showed a higher HBsAg-positive rate of
      6.9% in mid-western China (95% CI, 5.2-9.1%) against 5.6% in eastern China (95%
      CI, 4.9-6.4%). CONCLUSION: This meta-analysis suggested that the positive rates
      of HBsAg in China are reducing compared with previous 2006 sero-survey results,
      and China has changed from a high endemic area for HBV to an intermediate endemic
      area. However, owing to the large population, there remain an estimated 80
      million HBsAg carriers in China. Thus, the prevention and control of hepatitis B
      represent a serious challenge, particularly in mid-western China.

PMID- 26305712
TI  - Tobacco Use Among Siblings of Childhood Cancer Survivors: A Report From the
      Childhood Cancer Survivor Study.
AB  - BACKGROUND: Having a brother or sister with childhood cancer may influence health
      behaviors during adulthood. The aim of this study was to compare tobacco use in
      siblings of survivors with peers and to identify factors associated with sibling
      tobacco use. PROCEDURES: A retrospective cohort study was conducted using adult
      siblings (N = 1,974) of 5+ year cancer survivors in the Childhood Cancer Survivor
      Study (CCSS) and participants (N = 24,105, weighted to match CCSS) in the 2007
      National Health Interview Survey. Self-reported tobacco use, sociodemographic,
      and cancer-related risk factors were analyzed. RESULTS: Siblings were equally
      likely to have ever smoked compared to their peers (odds ratio [OR] 1.02, 95%
      confidence interval [CI] 0.93-1.12). Siblings were less likely to be current
      smokers (OR 0.83, 95%CI 0.73-0.94), but more likely to be former smokers (OR
      1.21, 95%CI 1.08-1.35). Siblings with low education were more likely to ever
      smoke (OR 1.51, 95%CI 1.15-2.00) and be current smokers (OR 1.67, 95%CI 1.24
      2.26) compared to their peers. Among siblings, risk factors for current tobacco
      use included the following: low income <$20,000 (OR 1.66, 95%CI 1.09-2.54), low
      education (OR 6.68, 95%CI 4.07-10.97), psychological distress (OR 5.36, 95%CI
      2.21-13.02), and heavy alcohol use (OR 3.68, 95%CI 2.50-5.41). CONCLUSIONS:
      Siblings of survivors take up smoking at similar rates to their peers, but are
      more likely to quit. Efforts are needed to address disparities by providing
      greater psychosocial support and education for the lowest socioeconomic status
      families facing childhood cancer.

PMID- 26305717
TI  - Ionic Charge Transfer Complex Induced Visible Light Harvesting and Photocharge
      Generation in Perovskite.
AB  - Organometal trihalide perovskite has recently emerged as a new class of promising
      material for high efficiency solar cells applications. While excess ions in
      perovskites are recently getting a great deal of attention, there is so far no
      clear understanding on both their formation and relating ions interaction to the
      photocharge generation in perovskite. Herein, we showed that tremendous ions
      indeed form during the initial stage of perovskite formation when the organic
      methylammonium halide (MAXa, Xa=Br and I) meets the inorganic PbXb2 (Xb=Cl, Br,
      I). The strong charge exchanges between the Pb2+ cations and Xa- anions result in
      formation of ionic charge transfer complexes (iCTC). MAXa parties induce empty
      valence electronic states within the forbidden bandgap of PbXb2. The strong
      surface dipole provide sufficient driving force for sub-bandgap electron
      transition with energy identical to the optical bandgap of forming perovskites.
      Evidences from XPS/UPS and photoluminescence studies showed that the light
      absorption, exciton dissociation, and photocharge generation of the perovskites
      are closely related to the strong ionic charge transfer interactions between Pb2+
      and Xa- ions in the perovskite lattices. Our results shed light on mechanisms of
      light harvesting and subsequent free carrier generation in perovskites.

PMID- 26305715
TI  - Curcumin attenuates ethanol-induced hepatic steatosis through modulating Nrf2/FXR
      signaling in hepatocytes.
AB  - Alcoholic liver disease (ALD) is a common health problem worldwide, characterized
      by aberrant accumulation of lipid in hepatocytes. Inhibition of lipid
      accumulation has been well recognized as a promising strategy for ALD. Previous
      studies showed that curcumin has potential effect on ALD by regulating oxidative
      stress and ethanol metabolism. However, the effects of curcumin on lipid
      accumulation and its mechanism remain unclear. Recent researches have indicated
      that farnesoid X receptor (FXR) and nuclear factor (erythroid-derived 2)-like 2
      (Nrf2) have excellent effects on reducing lipid deposition. This study
      demonstrated that curcumin alleviated ethanol-induced liver injury by
      ameliorating activities of serum marker enzymes and inflammation. Moreover,
      curcumin alleviated the symptom of hyperlipidemia and hepatic steatosis via
      modulating the expression of sterol regulatory element-binding protein-1c, fatty
      acid synthase, and peroxisome proliferator-activated receptor-alpha as well as
      the activity of carnitine palmitoyltransferase 1. Additionally, curcumin induced
      the expression of Nrf2 and FXR in liver, strongly implying close relationship
      between inhibitory effect of curcumin on hepatic steatosis and the above two
      genes. The following in vitro experiments further verified the protective effects
      of curcumin against hepatotoxicity and lipid accumulation in hepatocytes induced
      by ethanol. Gain- or loss-of-function analyses revealed Nrf2 and FXR mediated the
      effect of curcumin on lipid deposition in hepatocytes, and curcumin modulated the
      expression of FXR mediated by Nrf2. Collectively, we drew a conclusion that
      curcumin attenuated ALD by modulating lipid deposition in hepatocytes via a
      Nrf2/FXR activation-dependent mechanism. The findings make curcumin a potential
      agent for ALD and broaden the horizon of the molecular mechanism involved.

PMID- 26305718
TI  - Direct Measurement of the Nanomechanical Stability of a Redox Protein Active Site
      and Its Dependence upon Metal Binding.
AB  - The structural basis of the low reorganization energy of cupredoxins has long
      been debated. These proteins reconcile a conformationally heterogeneous and
      exposed metal-chelating site with the highly rigid copper center required for
      efficient electron transfer. Here we combine single-molecule mechanical unfolding
      experiments with statistical analysis and computer simulations to show that the
      metal-binding region of apo-azurin is mechanically flexible and that high
      mechanical stability is imparted by copper binding. The unfolding pathway of the
      metal site depends on the pulling residue and suggests that partial unfolding of
      the metal-binding site could be facilitated by the physical interaction with
      certain regions of the redox protein. 

PMID- 26305719
TI  - Influence of the Reactants Rotational Excitation on the H + D2(v = 0, j)
      Reactivity.
AB  - We have analyzed the influence of the rotational excitation on the H + D2(v = 0,
      j) reaction through quantum mechanical (QM) and quasiclassical trajectories (QCT)
      calculations at a wide range of total energies. The agreement between both types
      of calculations is excellent. We have found that the rotational excitation
      largely increases the reactivity at large values of the total energy. Such an
      increase cannot be attributed to a stereodynamical effect but to the existence of
      recrossing trajectories that become reactive as the target molecule gets
      rotationally excited. At low total energies, however, recrossing is not
      significant and the reactivity evolution is dominated by changes in the collision
      energy; the reactivity decreases with the collision energy as it shrinks the
      acceptance cone. When state-to-state results are considered, rotational
      excitation leads to cold product's rovibrational distributions, so that most of
      the energy is released as recoil energy. 

PMID- 26305720
TI  - Targeting vascular leakage in lung inflammation.

PMID- 26305721
TI  - Sonic Hedgehog: a lipid speciated hormone?

PMID- 26305722
TI  - MAPK phosphatase 5 inhibits IRF3.

PMID- 26305723
TI  - Sortilin and atherosclerosis.

PMID- 26305725
TI  - Animal models for breast cancer metastasis to bone: opportunities and
      limitations.
AB  - Skeletal metastases occur frequently in patients with breast cancer and are
      associated with significant morbidity and poor survival. Numerous animal models
      have been developed to investigate the biology of bone metastases and effective
      preventative or therapeutic approaches. However, no single animal model
      recapitulates the complexity of the metastatic process in toto. Therefore,
      selection of the animal model most appropriate for the question under
      investigation is crucial for the validity of the experimental outcome. This
      review provides an overview of the currently available animal models for breast
      cancer metastasis to bone with an emphasis on innovative xenograft models and
      imaging technologies. 

PMID- 26305724
TI  - The anticancer immune response of anti-PD-1/PD-L1 and the genetic determinants of
      response to anti-PD-1/PD-L1 antibodies in cancer patients.
AB  - The programmed death-1 (PD-1), a coinhibitory receptor expressed on activated T
      cells and B cells, is demonstrated to induce an immune-mediated response and play
      a critical role in tumor initiation and development. The cancer patients
      harboring PD-1 or PD ligand 1 (PD-L1) protein expression have often a poor
      prognosis and clinical outcome. Currently, targeting PD-1 pathway as a potential
      new anticancer strategy is attracting more and more attention in cancer
      treatment. Several monoclonal antibodies against PD-1 or PD-L1 have been reported
      to enhance anticancer immune responses and induce tumor cell death. Nonetheless,
      the precise molecular mechanisms by which PD-1 affects various cancers remain
      elusive. Moreover, this therapy is not effective for all the cancer patients and
      only a fraction of patients respond to the antibodies targeting PD-1 or PD-L1,
      indicating these antibodies may only works in a subset of certain cancers. Thus,
      understanding the novel function of PD-1 and genetic determinants of response to
      anti-PD-1 therapy will allow us to develop a more effective and individualized
      immunotherapeutic strategy for cancer. 

PMID- 26305727
TI  - Topical Application of Angelica sinensis Improves Pruritus and Skin Inflammation
      in Mice with Atopic Dermatitis-Like Symptoms.
AB  - Angelica sinensis (AS) is one of the most popular medicinal foods used as a
      hematopoietic herb and also traditionally applied topically for skin disorders.
      However, the effectiveness of AS on atopic dermatitis (AD) has not been reported
      yet. This study was conducted to evaluate the antipruritic and anti-inflammatory
      effects of AS on regulating AD-related mediators in DNCB (2,4
      dinitrochlorobenzene)-induced mice. AS was topically applied to the dorsal skin
      of DNCB-challenged mice for 11 days. Alteration of skin thickness was measured
      for assessment of histological improvement. In addition, the number of mast
      cells, the level of serum immunoglobulin E (IgE), the counting of scratching
      behavior, and the expression of substance P were evaluated. Also, the expressions
      of cytokines, nuclear factor kappaB (NF-kappaB), phospho-IkappaBalpha, and
      mitogen-activated protein kinases (MAPKs) were measured for evaluating the
      improvement of skin inflammation. The repeated treatment of AS significantly
      inhibited the skin thickness, the number of mast cells, and the level of serum
      IgE. Moreover, AS significantly suppressed the increased scratching behavior and
      the expression of substance P compared to the DNCB group. Topical application of
      AS also reduced the level of cytokines (IL-4, IL-6, TNF-alpha, and IFN-gamma) as
      well as the expressions of NF-kappaB, phospho-IkappaBalpha, and phospho-MAPKs in
      the dorsal skin. The results of our study suggest that topical application of AS
      might have efficacy for modulating pruritus and inflammation in AD. Further
      studies are required to further characterize the mechanism of actions of AS. 

PMID- 26305726
TI  - Differences in Weight-Related Behavioral Profiles by Sexual Orientation Among
      College Men: A Latent Class Analysis.
AB  - PURPOSE: To identify and describe homogenous classes of male college students
      based on their weight-related behaviors (e.g., eating habits, physical activity,
      and unhealthy weight control) and to examine differences by sexual orientation.
      DESIGN: Study design was a cross-sectional sample of 2- and 4-year college
      students. SETTING: Study setting was forty-six 2- and 4-year colleges in
      Minnesota. SUBJECTS: Study subjects comprised 10,406 college males. MEASURES:
      Measures were five categories of sexual orientation derived from self-reported
      sexual identity and behavior (heterosexual, discordant heterosexual [identifies
      as heterosexual and engages in same-sex sexual behavior], gay, bisexual, and
      unsure) and nine weight-related behaviors (including measures for eating habits,
      physical activity, and unhealthy weight control). ANALYSIS: Latent class models
      were fit for each of the five sexual orientation groups, using the nine weight
      related behaviors. RESULTS: Overall, four classes were identified: "healthier
      eating habits" (prevalence range, 39.4%-77.3%), "moderate eating habits" (12.0%
      30.2%), "unhealthy weight control" (2.6%-30.4%), and "healthier eating habits,
      more physically active" (35.8%). Heterosexual males exhibited all four patterns,
      gay and unsure males exhibited four patterns that included variations on the
      overall classes identified, discordant heterosexual males exhibited two patterns
      ("healthier eating habits" and "unhealthy weight control"), and bisexual males
      exhibited three patterns ("healthier eating habits," "moderate eating habits,"
      and "unhealthy weight control"). CONCLUSION: Findings highlight the need for
      multibehavioral interventions for discordant heterosexual, gay, bisexual, and
      unsure college males, particularly around encouraging physical activity and
      reducing unhealthy weight control behaviors.

PMID- 26305728
TI  - The Role of Interface on the Impact Characteristics and Cranial Fracture Patterns
      Using the Immature Porcine Head Model.
AB  - The role of impact interface characteristics on the biomechanics and patterns of
      cranial fracture has not been investigated in detail, and especially for the
      pediatric head. In this study, infant porcine skulls aged 2-19 days were dropped
      with an energy to cause fracturing onto four surfaces varying in stiffness from a
      rigid plate to one covered with plush carpeting. Results showed that heads
      dropped onto the rigid surface produced more extensive cranial fracturing than
      onto carpeted surfaces. Contact forces generated at fracture initiation and the
      overall maximum contact forces were generally lower for the rigid than carpeted
      impacts. While the degree of cranial fracturing from impacts onto the heavy
      carpeted surface was comparable to that of lower-energy rigid surface impacts,
      there were fewer diastatic fractures. This suggests that characteristics of the
      cranial fracture patterns may be used to differentiate energy level from impact
      interface in pediatric forensic cases. 

PMID- 26305729
TI  - Current status of pig kidney xenotransplantation.
AB  - Significant progress in life-supporting kidney xenograft survival in nonhuman
      primates (NHPs) has been associated largely with the increasing availability of
      pigs with genetic modifications that protect the pig tissues from the primate
      immune response and/or correct molecular incompatibilities between pig and
      primate. Blockade of the CD40/CD154 costimulation pathway with anti-CD154 mAb
      therapy has contributed to prolongation of kidney xenograft survival, although
      this agent may not be clinically available. An anti-CD40 mAb-based regimen is
      proving equally successful, but blockade of the CD28/B7 pathway is inadequate.
      Severe proteinuria were uniformly documented in the early studies of pig kidney
      xenotransplantation, but whether this resulted from immune injury or from
      physiological incompatibilities between the species, or both, remained uncertain.
      Recent experiments suggest it was related to a continuing immune response. Before
      2014, the longest survival of a pig kidney graft in a NHP was 90 days, though
      graft survival >30 days was unusual. Recently this has been extended to >125
      days, without features of a consumptive coagulopathy or a protein-losing
      nephropathy. In conclusion, overcoming the immune, coagulation, and inflammatory
      responses by the development of precise genetic modifications in donor pigs,
      along with effective immunosuppressive and anticoagulant/anti-inflammatory
      therapy is advancing the field towards clinical trials. 

PMID- 26305731
TI  - Ballistic Energy Transport in Oligomers.
AB  - The development of nanocomposite materials with desired heat management
      properties, including nanowires, layered semiconductor structures, and self
      assembled monolayer (SAM) junctions, attracts broad interest. Such materials
      often involve polymeric/oligomeric components and can feature high or low thermal
      conductivity, depending on their design. For example, in SAM junctions made of
      alkane chains sandwiched between metal layers, the thermal conductivity can be
      very low, whereas the fibers of ordered polyethylene chains feature high thermal
      conductivity, exceeding that of many pure metals. The thermal conductivity of
      nanostructured materials is determined by the energy transport between and within
      each component of the material, which all need to be understood for optimizing
      the properties. For example, in the SAM junctions, the energy transport across
      the metal-chain interface as well as the transport through the chains both
      determine the overall heat conductivity, however, to separate these contributions
      is difficult. Recently developed relaxation-assisted two-dimensional infrared (RA
      2DIR) spectroscopy is capable of studying energy transport in individual
      molecules in the time domain. The transport in a molecule is initiated by
      exciting an IR-active group (a tag); the method records the influence of the
      excess energy on another mode in the molecule (a reporter). The energy transport
      time can be measured for different reporters, and the transport speed through the
      molecule is evaluated. Various molecules were interrogated by RA 2DIR: in
      molecules without repeating units (disordered), the transport mechanism was
      expected and found to be diffusive. The transport via an oligomer backbone can
      potentially be ballistic, as the chain offers delocalized vibrational states.
      Indeed, the transport regime via three tested types of oligomers, alkanes,
      polyethyleneglycols, and perfluoroalkanes was found to be ballistic, whereas the
      transport within the end groups was diffusive. Interestingly, the transport
      speeds via these chains were different. Moreover, the transport speed was found
      to be dependent on the vibrational mode initiating the transport. For the
      difference in the transport speeds to be explained, the chain bands involved in
      the wavepacket formation were analyzed, and specific optical bands of the chain
      were identified as the energy transporters. For example, the transport initiated
      in alkanes by the stretching mode of the azido end group (2100 cm(-1)) occurs
      predominantly via the CH2 twisting and wagging chain bands, but the transport
      initiated by the C=O stretching modes of the carboxylic acid or succinimide ester
      end groups occurs via C-C stretching and CH2 rocking bands of the alkane chain.
      Direct formation of the wavepacket within the CH2 twisting and wagging chain
      bands occurs when the transport is initiated by the N?N stretching mode (1270 cm
      1) of the azido end-group. The transport via optical chain bands in oligomers
      involves rather large vibrational quanta (700-1400 cm(-1)), resulting in
      efficient energy delivery to substantial distances. Achieved quantitative
      description of various energy transport steps in oligomers, including the
      specific contributions of different chain bands, can result in a better
      understanding of the transport steps in nanocomposite materials, including SAM
      junctions, and lead towards designing systems for molecular electronics with a
      controllable energy transport speed. 

PMID- 26305732
TI  - Detection of DNA damage in cumulus cells using a chromatin dispersion assay.
AB  - DNA damage in cumulus cells (CCs) might be related with the developmental
      competence of the enclosed oocytes, however, conclusive studies are missing,
      partially due to the lack of a reliable, cheap, fast, and reproducible DNA damage
      test. We report the development of a chromatin dispersion test that allows for a
      fast evaluation of double strand DNA (ds-DNA) damage in CCs. The whole experiment
      was performed using CCs from 103 oocyte retrieval cycles evaluating the prototype
      D3-MAX ability (a chromatin dispersion based assay) to detect DNA breaks against
      in situ nick translation (ISNT) and a two tailed comet assay (TT-comet). Samples
      were collected from women younger than 35 years of age with a good response to
      stimulation. Pooled cumulus cells of MII oocytes were used. The chromatin
      dispersion assay results correlate with the double strand-DNA breaks values
      assessed by the TT-comet assay (Spearman Rho = 0.624; p = 0.003;), while the
      correlation was poor when compared to the single strand DNA (ss-DNA) breaks
      observed also with the TT-comet assay (Spearman Rho = -0.141; p = 0.554). ISNT
      showed a correspondence in the same cells between enzymatic incorporation of
      modified nucleotides and halos of chromatin dispersion. We conclude that D3-Max
      test detects mainly ds-DNA breaks in cumulus cells and is a reliable, fast, and
      easy reproducible assay suitable for routine clinical practices once the
      influence on oocyte quality has been established.

PMID- 26305734
TI  - A low cost, high energy density, and long cycle life potassium-sulfur battery for
      grid-scale energy storage.
AB  - A potassium-sulfur battery using K(+) -conducting beta-alumina as the electrolyte
      to separate a molten potassium metal anode and a sulfur cathode is presented. The
      results indicate that the battery can operate at as low as 150  degrees C with
      excellent performance. This study demonstrates a new type of high-performance
      metal-sulfur battery that is ideal for grid-scale energy-storage applications. 

PMID- 26305733
TI  - Improving the permeability of lyophilized collagen-hydroxyapatite scaffolds for
      cell-based bone regeneration with a gelatin porogen.
AB  - Bone tissue engineering using biomaterial scaffolds and culture-expanded
      osteoprogenitor cells has been demonstrated in several studies; however, it is
      not yet a clinical reality. One challenge is the optimal design of scaffolds for
      cell delivery and the identification of scaffold parameters that can delineate
      success and failure in vivo. Motivated by a previous experiment in which a batch
      of lyophilized collagen-hydroxyapatite (HA) scaffolds displayed modest bone
      formation in vivo, despite having large pores and high porosity, we began to
      investigate the effect of scaffold permeability on bone formation. Herein, we
      fabricated scaffolds with a permeability of 2.17 +/- 1.63 * 10-9 m4 /(N s) and
      fourfold higher using a sacrificial gelatin porogen. Scaffolds were seeded with
      mouse bone marrow stromal cells carrying a fluorescent reporter for osteoblast
      differentiation and implanted into critical-size calvarial defects in
      immunodeficient mice. The porogen scaffold group containing a 1:1 ratio of solids
      to beads was significantly more radiopaque than the scaffold group without the
      bead porogen 3 weeks after implantation. Quantitative histomorphometry uncovered
      the same trend between the 1:1 group and scaffolds without porogen found in the
      radiographic data; however, this was not statistically significant here. Taken
      together, the X-ray and histology suggest that the 1:1 ratio of porogen to
      scaffold solids, resulting in a fourfold increase in permeability, may enhance
      bone formation when compared to scaffolds without porogen. Scaffold permeability
      can be a useful quality control measure before implantation and this practice
      should improve the consistency and efficacy of cell-based bone tissue
      engineering. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl
      Biomater, 104B: 1580-1590, 2016.

PMID- 26305735
TI  - Age does not matter: Memory complaints are related to negative affect throughout
      adulthood.
AB  - OBJECTIVES: Memory complaints are present in adults of all ages but are only
      weakly related to objective memory deficits, raising the question of what their
      presence may indicate. In older adults, memory complaints are moderately related
      to negative affect, but there is little research examining this relationship in
      young and middle-aged adults. This study examined whether memory complaints and
      negative affect were similarly related across the adult lifespan and in adults
      with varying levels of objective memory performance. METHOD: The sample included
      3798 healthy adults, aged 18 to 99, and was divided into five groups: young,
      middle-aged, young-old, old-old, and oldest-old adults. Participants completed
      questionnaire measures of memory complaints and negative affect (neuroticism and
      depressive and anxiety symptoms), in addition to lab measures of objective
      memory. RESULTS: Using structural equation models, we found that the relationship
      between memory complaints and negative affect was moderate in all the age groups,
      and there was no evidence for moderation by objective memory. CONCLUSION: For
      adults of all ages, perceived memory decline may be distressing and/or negative
      affect may lead to negative self-evaluations of memory.

PMID- 26305737
TI  - Differences in perceptual learning transfer as a function of training task.
AB  - A growing body of research--including results from behavioral psychology, human
      structural and functional imaging, single-cell recordings in nonhuman primates,
      and computational modeling--suggests that perceptual learning effects are best
      understood as a change in the ability of higher-level integration or association
      areas to read out sensory information in the service of particular decisions.
      Work in this vein has argued that, depending on the training experience, the
      "rules" for this read-out can either be applicable to new contexts (thus
      engendering learning generalization) or can apply only to the exact training
      context (thus resulting in learning specificity). Here we contrast learning tasks
      designed to promote either stimulus-specific or stimulus-general rules.
      Specifically, we compare learning transfer across visual orientation following
      training on three different tasks: an orientation categorization task (which
      permits an orientation-specific learning solution), an orientation estimation
      task (which requires an orientation-general learning solution), and an
      orientation categorization task in which the relevant category boundary shifts on
      every trial (which lies somewhere between the two tasks above). While the simple
      orientation-categorization training task resulted in orientation-specific
      learning, the estimation and moving categorization tasks resulted in significant
      orientation learning generalization. The general framework tested here--that task
      specificity or generality can be predicted via an examination of the optimal
      learning solution--may be useful in building future training paradigms with
      certain desired outcomes.

PMID- 26305736
TI  - Is improved contrast sensitivity a natural consequence of visual training?
AB  - Many studies have shown that training and testing conditions modulate specificity
      of visual learning to trained stimuli and tasks. In visually impaired
      populations, generalizability of visual learning to untrained stimuli/tasks is
      almost always reported, with contrast sensitivity (CS) featuring prominently
      among these collaterally-improved functions. To understand factors underlying
      this difference, we measured CS for direction and orientation discrimination in
      the visual periphery of three groups of visually-intact subjects. Group 1 trained
      on an orientation discrimination task with static Gabors whose luminance contrast
      was decreased as performance improved. Group 2 trained on a global direction
      discrimination task using high-contrast random dot stimuli previously used to
      recover motion perception in cortically blind patients. Group 3 underwent no
      training. Both forms of training improved CS with some degree of specificity for
      basic attributes of the trained stimulus/task. Group 1's largest enhancement was
      in CS around the trained spatial/temporal frequencies; similarly, Group 2's
      largest improvements occurred in CS for discriminating moving and flickering
      stimuli. Group 3 saw no significant CS changes. These results indicate that CS
      improvements may be a natural consequence of multiple forms of visual training in
      visually intact humans, albeit with some specificity to the trained visual
      domain(s). 

PMID- 26305738
TI  - Assessing the applied benefits of perceptual training: Lessons from studies of
      training working-memory.
AB  - In the 1980s to 1990s, studies of perceptual learning focused on the specificity
      of training to basic visual attributes such as retinal position and orientation.
      These studies were considered scientifically innovative since they suggested the
      existence of plasticity in the early stimulus-specific sensory cortex. Twenty
      years later, perceptual training has gradually shifted to potential applications,
      and research tends to be devoted to showing transfer. In this paper we analyze
      two key methodological issues related to the interpretation of transfer. The
      first has to do with the absence of a control group or the sole use of a test
      retest group in traditional perceptual training studies. The second deals with
      claims of transfer based on the correlation between improvement on the trained
      and transfer tasks. We analyze examples from the general intelligence literature
      dealing with the impact on general intelligence of training on a working memory
      task. The re-analyses show that the reports of a significantly larger transfer of
      the trained group over the test-retest group fail to replicate when transfer is
      compared to an actively trained group. Furthermore, the correlations reported in
      this literature between gains on the trained and transfer tasks can be replicated
      even when no transfer is assumed. 

PMID- 26305739
TI  - Downregulation of MiR-30a is Associated with Poor Prognosis in Lung Cancer.
AB  - BACKGROUND: Recent reports have suggested that miR-30a plays a tumor-suppressive
      role in various cancers. However, miR-30a has not been completely studied in non
      small lung cancer (NSCLC). Thus, the aim of the present study was to clarify the
      association between the expression of miR-30a and the clinicopathological
      features in NSCLC patients. MATERIAL AND METHODS: Total RNA of miR-30a was
      extracted from 125 pairs of NSCLC patients (male 75, female 50) and their
      matching normal tissues. The miR-30a level was detected by using quantitative
      real-time polymerase chain reaction (qRT-PCR). Simultaneously, the 2-DeltaCq
      method was used to calculate the correlation between miR-30a expression and the
      clinicopathological parameters and prognosis of NSCLC patients. RESULTS: MiR-30a
      expression was significantly down-regulated in NSCLC tissues (4.0696+/-2.4178)
      compared to their non-tumor lung tissues (7.4530+/-3.0561, P<0.001). Level of miR
      30a was negatively correlated to tumor size (r=-0.197, P=0.028), lymphatic
      metastasis (r=-0.312, P<0.001), clinical TNM stage (r=-0.299, P=0.001),
      pathological grading (I/II vs. III, r=-0.224, P=0.001), and histological
      classification (r=-0.299, P=0.001). Survival time was 3.23+/-2.18 months in the
      low miR-30a expression group, remarkably shorter than that of the high expression
      group (20.72+/-11.63 months, P<0.001). CONCLUSIONS: MiR-30a may be regarded as a
      tumor suppressor in NSCLC, and it could become a prognostic marker and potential
      therapeutic target for NSCLC.

PMID- 26305740
TI  - Prudentia Populo: Involving the Community in Biobank Governance.

PMID- 26305742
TI  - Is Shared Decision Making an Appropriate Analytic Frame for Research on Medical
      Practices?

PMID- 26305741
TI  - Patient Perspectives on the Learning Health System: The Importance of Trust and
      Shared Decision Making.
AB  - We conducted focus groups to assess patient attitudes toward research on medical
      practices in the context of usual care. We found that patients focus on the
      implications of this research for their relationship with and trust in their
      physicians. Patients view research on medical practices as separate from usual
      care, demanding dissemination of information and in most cases, individual
      consent. Patients expect information about this research to come through their
      physician, whom they rely on to identify and filter associated risks. In general,
      patients support this research, but worry that participation in research
      involving randomization may undermine individualized care that acknowledges their
      unique medical histories. These findings suggest the need for public education on
      variation in practice among physicians and the need for a collaborative approach
      to the governance of research on medical practices that addresses core values of
      trust, transparency, and partnership. 

PMID- 26305743
TI  - "I'm Really Torn, I Guess": Reconciling Conflicting Roles Among Physicians
      Seeking Research Consent.

PMID- 26305744
TI  - What's Trust Got to Do With It? Trust and the Importance of the Research-Care
      Distinction.

PMID- 26305745
TI  - The Reciprocity of Shared Decisions Across the Care Spectrum.

PMID- 26305746
TI  - The Importance of Trust and the Importance of Trustworthiness.

PMID- 26305747
TI  - Lost in Interpretation: Autonomy and What Patients Tell Versus What Is Inferred.

PMID- 26305748
TI  - Relying on Trust for Research on Medical Practice in Learning Health Systems.

PMID- 26305749
TI  - What Is the Right Way to Respect Patient Perspectives?

PMID- 26305751
TI  - Facilitating Autonomy With Broad Consent.

PMID- 26305750
TI  - Broad Consent for Research With Biological Samples: Workshop Conclusions.
AB  - Different types of consent are used to obtain human biospecimens for future
      research. This variation has resulted in confusion regarding what research is
      permitted, inadvertent constraints on future research, and research proceeding
      without consent. The National Institutes of Health (NIH) Clinical Center's
      Department of Bioethics held a workshop to consider the ethical acceptability of
      addressing these concerns by using broad consent for future research on stored
      biospecimens. Multiple bioethics scholars, who have written on these issues,
      discussed the reasons for consent, the range of consent strategies, and gaps in
      our understanding, and concluded with a proposal for broad initial consent
      coupled with oversight and, when feasible, ongoing provision of information to
      donors. This article describes areas of agreement and areas that need more
      research and dialogue. Given recent proposed changes to the Common Rule, and new
      guidance regarding storing and sharing data and samples, this is an important and
      timely topic. 

PMID- 26305752
TI  - Going Beyond the False Dichotomy of Broad or Specific Consent: A Meta-Perspective
      on Participant Choice in Research Using Human Tissue.

PMID- 26305753
TI  - Crushing Consent Under the Weight of Expectations.

PMID- 26305754
TI  - Love Thy Neighbor: Replacing Paternalistic Protection as the Grounds for Research
      Ethics.

PMID- 26305755
TI  - More Nuanced Informed Consent Is Not Necessarily Better Informed Consent.

PMID- 26305756
TI  - Broad Consent Is Consent for Governance.

PMID- 26305757
TI  - Linking Broad Consent to Biobank Governance: Support From a Deliberative Public
      Engagement in California.

PMID- 26305758
TI  - Consent to Biobank Research: Facing Up to the Challenge of Globalization.

PMID- 26305759
TI  - Research Guideline Recommendations for Broad Consent Forms in Biobank Research
      and How They Are Currently Addressed in Practice.

PMID- 26305760
TI  - The U.S. National Biobank and (No) Consensus on Informed Consent.

PMID- 26305761
TI  - In Favor of a No-Consent/Opt-Out Model of Research With Clinical Samples.

PMID- 26305762
TI  - Cascading Consent for Research on Biobank Specimens.

PMID- 26305763
TI  - Children, Biological Samples, and Broad Consent.

PMID- 26305764
TI  - Naming Indigenous Concerns, Framing Considerations for Stored Biospecimens.

PMID- 26305765
TI  - On the Value of Diversity.

PMID- 26305767
TI  - Response to Open Peer Commentaries on "Addressing Consent Issues in Donation
      After Circulatory Determination of Death".

PMID- 26305768
TI  - Response to Open Peer Commentaries on "The Texas Advanced Directive Law:
      Unfinished Business".

PMID- 26305770
TI  - Increased use of partial nephrectomy to treat high-risk disease.
AB  - OBJECTIVES: To evaluate partial nephrectomy (PN) use in patients at higher risk
      for clinical progression, using a large national database of American patients.
      PATIENTS AND METHODS: We performed a retrospective review of patients with
      cN0/cM0 renal cell carcinoma from 2003 to 2011 using the National Cancer Data
      Base. Our primary endpoint was PN use for high-risk disease, defined as >=1
      adverse pathological features (APF), namely pT3 stage, high grade, or
      unfavourable histology. Our secondary endpoint was positive surgical margins
      (PSM) associated with high-risk disease after PN. Time trends were analysed using
      the asymptotic Cochran-Armitage trend test. Relationships between patient,
      provider, and pathological factors and the likelihood of PN were assessed using
      multivariate logistic regression. RESULTS: Of 183 886 surgically treated
      patients, 27.4% underwent PN. Over time, PN use increased overall (17.4-39.7%)
      and in tumours with >=1 APF (8.5-24.2%) (P < 0.01). In patients with >=1 APF,
      multivariate analysis revealed that academic practice setting and high surgical
      volume were positively associated with PN use, while increasing tumour size and
      preoperative biopsy were negatively associated with its use (P < 0.01). The PSM
      rate after PN also increased significantly over time in all patients and in those
      harbouring adverse pathology (P < 0.01). Aside from time, older age, larger
      tumour size, community hospital type, and robotic approach were associated with
      PSM in the setting of APF (P < 0.01). CONCLUSION: PN use for patients with
      adverse pathology is increasing and is associated with increasing PSM. The long
      term oncological implications of these trends are unclear and warrant further
      study.

PMID- 26305771
TI  - Heart Rate, Life Expectancy and the Cardiovascular System: Therapeutic
      Considerations.
AB  - It has long been known that life span is inversely related to resting heart rate
      in most organisms. This association between heart rate and survival has been
      attributed to the metabolic rate, which is greater in smaller animals and is
      directly associated with heart rate. Studies have shown that heart rate is
      related to survival in apparently healthy individuals and in patients with
      different underlying cardiovascular diseases. A decrease in heart rate due to
      therapeutic interventions may result in an increase in survival. However, there
      are many factors regulating heart rate, and it is quite plausible that these may
      independently affect life expectancy. Nonetheless, a fast heart rate itself
      affects the cardiovascular system in multiple ways (it increases ventricular
      work, myocardial oxygen consumption, endothelial stress, aortic/arterial
      stiffness, decreases myocardial oxygen supply, other) which, in turn, may affect
      survival. In this brief review, the effects of heart rate on the heart, arterial
      system and survival will be discussed. 

PMID- 26305773
TI  - Fractal analysis: fractal dimension and lacunarity from MR images for
      differentiating the grades of glioma.
AB  - Glioma, the heterogeneous tumors originating from glial cells, generally exhibit
      varied grades and are difficult to differentiate using conventional MR imaging
      techniques. When this differentiation is crucial in the disease prognosis and
      treatment, even the advanced MR imaging techniques fail to provide a higher
      discriminative power for the differentiation of malignant tumor from benign ones.
      A powerful image processing technique applied to the imaging techniques is
      expected to provide a better differentiation. The present study focuses on the
      fractal analysis of fluid attenuation inversion recovery MR images, for the
      differentiation of glioma. For this, we have considered the most important
      parameters of fractal analysis, fractal dimension and lacunarity. While fractal
      analysis assesses the malignancy and complexity of a fractal object, lacunarity
      gives an indication on the empty space and the degree of inhomogeneity in the
      fractal objects. Box counting method with the preprocessing steps namely
      binarization, dilation and outlining was used to obtain the fractal dimension and
      lacunarity in glioma. Statistical analysis such as one-way analysis of variance
      and receiver operating characteristic (ROC) curve analysis helped to compare the
      mean and to find discriminative sensitivity of the results. It was found that the
      lacunarity of low and high grade gliomas vary significantly. ROC curve analysis
      between low and high grade glioma for fractal dimension and lacunarity yielded
      70.3% sensitivity and 66.7% specificity and 70.3% sensitivity and 88.9%
      specificity, respectively. The study observes that fractal dimension and
      lacunarity increases with an increase in the grade of glioma and lacunarity is
      helpful in identifying most malignant grades. 

PMID- 26305772
TI  - Rapid quantitative analysis of monoclonal antibody heavy and light chain charge
      heterogeneity.
AB  - An alternative method to traditional 2-dimensional gel electrophoresis (2D-PAGE)
      and its application in characterizing the inherent charge heterogeneity of
      chromatographically isolated monoclonal antibody heavy and light chains is
      described. This method, referred to as ChromiCE, utilizes analytical size
      exclusion chromatography (SEC), performed under reducing and denaturing
      conditions, followed by imaged capillary isoelectric focusing (icIEF) of the
      chromatographically separated heavy and light chains. Under conditions suitable
      for the subsequent icIEF analysis, the absolute and relative SEC elution volumes
      of the heavy and light chains were found to be highly pH dependent, a phenomenon
      that can be exploited in optimizing chromatographic separation. Compared to 2D
      PAGE, the ChromiCE method substantially decreases the time and labor needed to
      complete the analysis, improves reproducibility, and provides fully quantitative
      assessment of charge heterogeneity. The ChromiCE methodology was applied to a set
      of diverse monoclonal antibodies to demonstrate suitability for quantitative
      charge variant analysis of heavy and light chains. A typical application of
      ChromiCE in extended characterization and stability studies of a purified
      antibody is shown. 

PMID- 26305774
TI  - From the clinic to the field: Joint pulmonary medicine-environmental sciences
      laboratory investigations, 1973-1992 and beyond.

PMID- 26305775
TI  - Coordination Structure Conversion of Hydrazone-Palladium(II) Complexes in the
      Solid State and in Solution.
AB  - We prepared hydrazone-palladium(II) complexes of [PdCl2(HL(n))] and [PdCl(L(n))]
      (n = 1-3) by the reaction of [PdCl2(cod)] or [PdCl2(PhCN)2] and the hydrazone
      ligands of HL(n) {N'-(pyridin-2-ylmethylene)picolinohydrazide (HL(1)), N'-[1
      (pyridin-2-yl)ethylidene]picolinohydrazide (HL(2)), and N'-[(6-methylpyridin-2
      yl)methylene]picolinohydrazide (HL(3))}. The structures of the complexes were
      determined by X-ray analysis. The hydrazone ligands had kappaN(py1),kappaN(imine)
      and kappaN(amidate),kappaN(py2) bidentate coordination modes in [PdCl2(HL(n))]
      (1, n = 1; 2, n = 2) and in [PdCl2(HL(3))] (3), respectively. In contrast,
      tridentate coordination modes of kappaN(py1),kappaN(imine),kappaN(py2) and
      kappaN(py1),kappaN(amidate),kappaN(py2) were observed in [PdCl(L(n))] (4, n = 1;
      5, n = 2) and in [PdCl(L(n))] (6, n = 1; 7, n = 2; 8, n = 3). Thermal conversion
      of complexes 1-3 to complexes 6-8 proceeded in acetonitrile. Complexes 4 and 5
      were obtained from complexes 1 and 2, respectively, in a basic acetonitrile
      solution under dark conditions. Complex 4 reverted immediately to complex 1 in an
      acidic acetonitrile solution that included hydrochloric acid. However, under room
      light, in the basic acetonitrile solution that included trimethylamine, complex 4
      converted photochemically to complex 6. The thermochromic or vapochromic
      structure conversion of these complexes also occurred in the solid state. On
      heating at 180  degrees C, the color of the crystals of complexes 1, 2, and 3
      changed from yellow to orange in the solid state. (1)H NMR and/or UV-vis
      absorption spectroscopy confirmed that the orange complexes 6-8 were produced.
      The reddish-orange crystals of complexes 4 and 5 were exposed to hydrogen
      chloride vapor to yield the yellow products of complexes 1 and 2, respectively. 

PMID- 26305776
TI  - Generation of a synthetic GlcNAcylated nucleosome reveals regulation of stability
      by H2A-Thr101 GlcNAcylation.
AB  - O-GlcNAcylation is a newly discovered histone modification implicated in
      transcriptional regulation, but no structural information on the physical effect
      of GlcNAcylation on chromatin exists. Here, we generate synthetic, pure
      GlcNAcylated histones and nucleosomes and reveal that GlcNAcylation can modulate
      structure through direct destabilization of H2A/H2B dimers in the nucleosome,
      thus promoting an 'open' chromatin state. The results suggest that a plausible
      molecular basis for one role of histone O-GlcNAcylation in epigenetic regulation
      is to lower the barrier for RNA polymerase passage and hence increase
      transcription. 

PMID- 26305777
TI  - Measurement of Local Partial Pressure of Oxygen in the Brain Tissue under
      Normoxia and Epilepsy with Phosphorescence Lifetime Microscopy.
AB  - In this work a method for measuring brain oxygen partial pressure with confocal
      phosphorescence lifetime microscopy system is reported. When used in conjunction
      with a dendritic phosphorescent probe, Oxyphor G4, this system enabled minimally
      invasive measurements of oxygen partial pressure (pO2) in cerebral tissue with
      high spatial and temporal resolution during 4-AP induced epileptic seizures.
      Investigating epileptic events, we characterized the spatio-temporal distribution
      of the "initial dip" in pO2 near the probe injection site and along nearby
      arterioles. Our results reveal a correlation between the percent change in the
      pO2 signal during the "initial dip" and the duration of seizure-like activity,
      which can help localize the epileptic focus and predict the length of seizure. 

PMID- 26305778
TI  - A New Segmental Hepatectomy Approach Using Ultrasound-Guided Portal Branch
      Infusion of a Thermosensitive Gel in Pigs.
AB  - BACKGROUND: The aim of this study was to evaluate the safety, feasibility, and
      efficacy of a new segmental hepatectomy (SH) approach using intraoperative
      ultrasound (IOUS) guided infusion of a reversible thermosensitive gel into the
      portal vein branch in pigs; MATERIALS AND METHODS: Poloxamer 407 aqueous solution
      (20%, W/V) was mixed with indocyanine green (P407-ICG) in this study to make it
      green, and it remained liquid at room temperature and turned into a firm gel upon
      reaching body temperature. In experiment I, six pigs were used to detect the
      outcome of infusing the mixture into the biliary tract, liver parenchyma, and
      hepatic vein for a safety study. In experiment II, another 12 pigs were randomly
      segmented into two groups [SH group and partial hepatectomy (PH) group] to
      investigate the feasibility and efficacy of the new approach using IOUS-guided
      infusion of the mixture into the portal branch; RESULTS: No thermosensitive gel
      induced abnormal changes were observed in the safety study. In the SH group, IOUS
      guided infusion of the P407-ICG solution was effective in occluding the portal
      blood temporarily and demarcating the target liver segment to achieve precise SH.
      The blood loss in the SH group was significantly less than that of the PH group;
      CONCLUSIONS: SH assisted by IOUS-guided infusion of the reversible
      thermosensitive gel into the feeding portal vein branches is feasible, safe,
      simple, and effective.

PMID- 26305779
TI  - A big step forward in understanding global differences in respiratory health:
      first lung function data in African infants.

PMID- 26305780
TI  - From cyst to tubule: innovations in vertebrate spermatogenesis.
AB  - Although vertebrates share many common traits, their germline development and
      function exhibit significant divergence. In particular, this article focuses on
      their spermatogenesis. The fundamental elements that constitute vertebrate
      spermatogenesis and the evolutionary changes that occurred upon transition from
      water to land will be discussed. The life-long continuity of spermatogenesis is
      supported by the function of stem cells. Series of mitotic and meiotic germ cell
      divisions are 'incomplete' due to incomplete cytokinesis, forming syncytia
      interconnected via intercellular bridges (ICBs). Throughout this process, germ
      cells are supported by appropriate microenvironments established primarily by
      somatic Sertoli cells. In anamniotes (fish and amphibians) spermatogenesis
      progresses in cysts, in which developing germ cell syncytia are individually
      encapsulated by Sertoli cells. Accordingly, Sertoli cells undergo turnover with
      germ cells that they nourish. This mode of cystic spermatogenesis is also
      observed in nonvertebrates as insects. In amniotes (reptiles, birds, and
      mammals), however, Sertoli cells do not turn over but comprise a persistent
      structure of seminiferous tubules. Sertoli cells nourish different stages of germ
      cells simultaneously in distinct regions of their surface. This function of
      Sertoli cells is spatiotemporally orchestrated, and the seminiferous epithelial
      cycle and spermatogenic wave make the seminiferous tubules a high-throughput
      factory for sperm production. Furthermore, contrary to the organized
      differentiating cells, undifferentiated spermatogonia that comprise the stem cell
      compartment exhibit active motion over the basal layer of seminiferous tubules
      and the frequent breakdown of ICBs. Thus, amniote seminiferous tubules represent
      a typical facultative (or open) niche environment without a stem cell tethering
      anatomically defined niche. WIREs Dev Biol 2016, 5:119-131. doi: 10.1002/wdev.204
      For further resources related to this article, please visit the WIREs website. 

PMID- 26305781
TI  - Performance of a Novel Molecular Method in the Diagnosis of Late-Onset Sepsis in
      Very Low Birth Weight Infants.
AB  - OBJECTIVE: To compare the use of a generic molecular assay to 'standard'
      investigations used to assist the diagnosis of late onset bacterial sepsis in
      very low birth weight infants (VLBW, <1500 g). METHODS: VLBW infants, greater
      than 48 hours of age, who were clinically suspected to have sepsis were
      investigated using standard tests (full blood count, C-reactive protein (at
      presentation) and blood culture), in addition, blood was taken for a universal
      molecular assay (16S rRNA reverse transcriptase PCR) for comparison. Clinical
      data were recorded during the suspected infection episode. A validated sepsis
      score (NEO-KISS) was used to retrospectively determine the presence of sepsis
      (independent of blood culture). The performance of each of the tests were
      compared by sensitivity, specificity, positive/negative likihood ratios (+/-LR)
      and postive/negative predictive values (PPV/NPV). RESULTS: Sixty-five babies with
      suspected clinical sepsis were prospectively included. The performance indicators
      are presented with 95% confidence limits. For the detection of bacteria, blood
      culture had sensitivity of 0.57 (0.34-0.78), specificity of 0.45 (0.30-0.61); +LR
      of 1.05 (0.66-1.66) and-LR of 0.94 (0.52-1.7); PPV of 33.3 (18.56-50.97) and NPV
      of 68.97 (49.17-87.72). Serum CRP had sensitivity of 0.92 (0.64-1) and
      specificity of 0.36 (0.17-0.59); +LR of 1.45 (1-2.1) and-LR of 0.21 (0.03-1.5);
      PPV of 44.46 (26.6-66.6) and NPV of 88.9 (51.8-99.7). The universal molecular
      assay had sensitivity of 0.76 (0.53-0.92), specificity of 0.95 (0.85-0.99); +LR
      of 16.8 (4.2-66.3) and-LR of 0.25 (0.1-0.5); PPV of 88.9 (65.3-98.6) and NPV of
      89.4 (76.9-96.5). CONCLUSIONS: In VLBW infants this universal molecular assay
      performed better in the diagnosis of late onset sepsis (LOS) than blood culture
      and CRP. Further development is required to explore and improve the performance
      of the assay in real-time diagnosis.

PMID- 26305783
TI  - Correction: Correction: Hypothermia and Rewarming Induce Gene Expression and
      Multiplication of Cells in Healthy Rat Prostate Tissue.

PMID- 26305782
TI  - Beta-Lactamase Repressor BlaI Modulates Staphylococcus aureus Cathelicidin
      Antimicrobial Peptide Resistance and Virulence.
AB  - BlaI is a repressor of BlaZ, the beta-lactamase responsible for penicillin
      resistance in Staphylococcus aureus. Through screening a transposon library in S.
      aureus Newman for susceptibility to cathelicidin antimicrobial peptide, we
      discovered BlaI as a novel cathelicidin resistance factor. Additionally, through
      integrational mutagenesis in S. aureus Newman and MRSA Sanger 252 strains, we
      confirmed the role of BlaI in resistance to human and murine cathelidicin and
      showed that it contributes to virulence in human whole blood and murine infection
      models. We further demonstrated that BlaI could be a target for innate immune
      based antimicrobial therapies; by removing BlaI through subinhibitory
      concentrations of 6-aminopenicillanic acid, we were able to sensitize S. aureus
      to LL-37 killing. 

PMID- 26305784
TI  - One new cycloartane triterpene glycoside from Beesia calthaefolia.
AB  - One new cycloartane triterpene glycoside (1) was isolated from the whole plant of
      Beesia calthaefolia. Its structure was elucidated on the basis of extensive
      spectroscopic data analysis. Its inhibitory effect was measured by the classical
      pathway of the complement system, and compared with those of known related
      cycloartane glycosides 2 and 3, previously isolated by us from the same plant.
      Compounds 1 and 2 exhibited inhibitory activity of complement system with IC50 of
      395.3 and 214 MUM, respectively. The results suggested that OH at C-12, C-18 and
      C-15 along with the polarity could affect the inhibitory activity.

PMID- 26305785
TI  - Workplace Bullying and Mental Health: A Meta-Analysis on Cross-Sectional and
      Longitudinal Data.
AB  - BACKGROUND: A growing body of research has confirmed that workplace bullying is a
      source of distress and poor mental health. Here we summarize the cross-sectional
      and longitudinal literature on these associations. METHODS: Systematic review and
      meta-analyses on the relation between workplace bullying and mental health.
      RESULTS: The cross-sectional data (65 effect sizes, N = 115.783) showed positive
      associations between workplace bullying and symptoms of depression (r = .28, 95%
      CI = .23-.34), anxiety (r = .34, 95% CI = .29-.40) and stress-related
      psychological complaints (r = .37, 95% CI = .30-.44). Pooling the literature that
      investigated longitudinal relationships (26 effect sizes, N = 54.450) showed that
      workplace bullying was related to mental health complaints over time (r = 0.21,
      95% CI = 0.13-0.21). Interestingly, baseline mental health problems were
      associated with subsequent exposure to workplace bullying (r = 0.18, 95% CI =
      0.10-0.27; 11 effect sizes, N = 27.028). LIMITATIONS: All data were self
      reported, raising the possibility of reporting- and response set bias.
      CONCLUSIONS: Workplace bullying is consistently, and in a bi-directional manner,
      associated with reduced mental health. This may call for intervention strategies
      against bullying at work.

PMID- 26305786
TI  - Cyclooxygenase-2 and Prostaglandin E2 Signaling through Prostaglandin Receptor EP
      2 Favor the Development of Myocarditis during Acute Trypanosoma cruzi Infection.
AB  - Inflammation plays an important role in the pathophysiology of Chagas disease,
      caused by Trypanosoma cruzi. Prostanoids are regulators of homeostasis and
      inflammation and are produced mainly by myeloid cells, being cyclooxygenases, COX
      1 and COX-2, the key enzymes in their biosynthesis from arachidonic acid (AA).
      Here, we have investigated the expression of enzymes involved in AA metabolism
      during T. cruzi infection. Our results show an increase in the expression of
      several of these enzymes in acute T. cruzi infected heart. Interestingly, COX-2
      was expressed by CD68+ myeloid heart-infiltrating cells. In addition,
      infiltrating myeloid CD11b+Ly6G- cells purified from infected heart tissue
      express COX-2 and produce prostaglandin E2 (PGE2) ex vivo. T. cruzi infections in
      COX-2 or PGE2-dependent prostaglandin receptor EP-2 deficient mice indicate that
      both, COX-2 and EP-2 signaling contribute significantly to the heart leukocyte
      infiltration and to the release of chemokines and inflammatory cytokines in the
      heart of T. cruzi infected mice. In conclusion, COX-2 plays a detrimental role in
      acute Chagas disease myocarditis and points to COX-2 as a potential target for
      immune intervention. 

PMID- 26305787
TI  - The Evolutionarily Conserved LIM Homeodomain Protein LIM-4/LHX6 Specifies the
      Terminal Identity of a Cholinergic and Peptidergic C. elegans Sensory/Inter/Motor
      Neuron-Type.
AB  - The expression of specific transcription factors determines the differentiated
      features of postmitotic neurons. However, the mechanism by which specific
      molecules determine neuronal cell fate and the extent to which the functions of
      transcription factors are conserved in evolution are not fully understood. In C.
      elegans, the cholinergic and peptidergic SMB sensory/inter/motor neurons
      innervate muscle quadrants in the head and control the amplitude of sinusoidal
      movement. Here we show that the LIM homeobox protein LIM-4 determines neuronal
      characteristics of the SMB neurons. In lim-4 mutant animals, expression of
      terminal differentiation genes, such as the cholinergic gene battery and the flp
      12 neuropeptide gene, is completely abolished and thus the function of the SMB
      neurons is compromised. LIM-4 activity promotes SMB identity by directly
      regulating the expression of the SMB marker genes via a distinct cis-regulatory
      motif. Two human LIM-4 orthologs, LHX6 and LHX8, functionally substitute for LIM
      4 in C. elegans. Furthermore, C. elegans LIM-4 or human LHX6 can induce
      cholinergic and peptidergic characteristics in the human neuronal cell lines. Our
      results indicate that the evolutionarily conserved LIM-4/LHX6 homeodomain
      proteins function in generation of precise neuronal subtypes. 

PMID- 26305788
TI  - Familiar Face Detection in 180 ms.
AB  - The visual system is tuned for rapid detection of faces, with the fastest choice
      saccade to a face at 100 ms. Familiar faces have a more robust representation
      than do unfamiliar faces, and are detected faster in the absence of awareness and
      with reduced attentional resources. Faces of family and close friends become
      familiar over a protracted period involving learning the unique visual
      appearance, including a view-invariant representation, as well as person
      knowledge. We investigated the effect of personal familiarity on the earliest
      stages of face processing by using a saccadic-choice task to measure how fast
      familiar face detection can happen. Subjects made correct and reliable saccades
      to familiar faces when unfamiliar faces were distractors at 180 ms--very rapid
      saccades that are 30 to 70 ms earlier than the earliest evoked potential
      modulated by familiarity. By contrast, accuracy of saccades to unfamiliar faces
      with familiar faces as distractors did not exceed chance. Saccades to faces with
      object distractors were even faster (110 to 120 ms) and equivalent for familiar
      and unfamiliar faces, indicating that familiarity does not affect ultra-rapid
      saccades. We propose that detectors of diagnostic facial features for familiar
      faces develop in visual cortices through learning and allow rapid detection that
      precedes explicit recognition of identity.

PMID- 26305791
TI  - Correction: Circulating miR-19a and miR-205 in Serum May Predict the Sensitivity
      of Luminal A Subtype of Breast Cancer Patients to Neoadjuvant Chemotherapy with
      Epirubicin Plus Paclitaxel.

PMID- 26305789
TI  - Detection of chromothripsis-like patterns with a custom array platform for
      chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is a common disease with highly variable
      clinical course. Several recurrent chromosomal alterations are associated with
      prognosis and may guide risk-adapted therapy. We have developed a targeted genome
      wide array to provide a robust tool for ascertaining abnormalities in CLL and to
      overcome limitations of the 4-marker fluorescence in situ hybridization (FISH).
      DNA from 180 CLL patients were hybridized to the qChip(r)Hemo array with a high
      density of probes covering commonly altered loci in CLL (11q22-q23, 13q14, and
      17p13), nine focal regions (2p15-p16.1, 2p24.3, 2q13, 2q36.3-q37.1, 3p21.31,
      8q24.21, 9p21.3, 10q24.32, and 18q21.32-q21.33) and two larger regions (6q14.1
      q22.31 and 7q31.33-q33). Overall, 86% of the cases presented copy number
      alterations (CNA) by array. There was a high concordance of array findings with
      FISH (84% sensitivity, 100% specificity); all discrepancies corresponded to
      subclonal alterations detected only by FISH. A chromothripsis-like pattern was
      detected in eight cases. Three showed concomitant shattered 5p with gain of TERT
      along with isochromosome 17q. Presence of 11q loss was associated with shorter
      time to first treatment (P = 0.003), whereas 17p loss, increased genomic
      complexity, and chromothripsis were associated with shorter overall survival (P <
      0.001, P = 0.001, and P = 0.02, respectively). In conclusion, we have validated a
      targeted array for the diagnosis of CLL that accurately detects, in a single
      experiment, all relevant CNAs, genomic complexity, chromothripsis, copy number
      neutral loss of heterozygosity, and CNAs not covered by the FISH panel. This test
      may be used as a practical tool to stratify CLL patients for routine diagnostics
      or clinical trials.

PMID- 26305792
TI  - Scalable Growth of High Mobility Dirac Semimetal Cd3As2 Microbelts.
AB  - Three-dimensional (3D) Dirac semimetals are 3D analogues of graphene, which
      display Dirac points with linear dispersion in k-space, stabilized by crystal
      symmetry. Cd3As2 has been predicted to be 3D Dirac semimetals and was
      subsequently demonstrated by angle-resolved photoemission spectroscopy. As
      unveiled by transport measurements, several exotic phases, such as Weyl
      semimetals, topological insulators, and topological superconductors, can be
      deduced by breaking time reversal or inversion symmetry. Here, we reported a
      facile and scalable chemical vapor deposition method to fabricate high-quality
      Dirac semimetal Cd3As2 microbelts; they have shown ultrahigh mobility up to 1.15
      * 10(5) cm(2) V(-1) s(-1) and pronounced Shubnikov-de Haas oscillations. Such
      extraordinary features are attributed to the suppression of electron
      backscattering. This research opens a new avenue for the scalable fabrication of
      Cd3As2 materials toward exciting electronic applications of 3D Dirac semimetals. 

PMID- 26305790
TI  - Pelvic Belt Effects on Health Outcomes and Functional Parameters of Patients with
      Sacroiliac Joint Pain.
AB  - INTRODUCTION: The sacroiliac joint (SIJ) is a common source of low back pain.
      However, clinical and functional signs and symptoms correlating with SIJ pain are
      widely unknown. Pelvic belts are routinely applied to treat SIJ pain but without
      sound evidence of their pain-relieving effects. This case-control study compares
      clinical and functional data of SIJ patients and healthy control subjects and
      evaluates belt effects on SIJ pain. METHODS: 17 SIJ patients and 17 healthy
      controls were included in this prospective study. The short-form 36 survey and
      the numerical rating scale were used to characterize health-related quality of
      life in patients in a six-week follow-up and the pain-reducing effects of pelvic
      belts. Electromyography data were obtained from the gluteus maximus, biceps
      femoris, rectus femoris and medial vastus. Alterations of muscle activity,
      variability and gait patterns were compared in patients and controls along with
      the belts' effects in a dynamic setting when walking. RESULTS: Significant
      improvements were observed in the short-form 36 survey of the SIJ patients,
      especially in the physical health subscores. Minor declines were also observed in
      the numerical rating scale on pain. Belt-related changes of muscle activity and
      variability were similar in patients and controls with one exception: the rectus
      femoris activity decreased significantly in patients with belt application when
      walking. Further belt effects include improved cadence and gait velocity in
      patients and controls. CONCLUSIONS: Pelvic belts improve health-related quality
      of life and are potentially attributed to decreased SIJ-related pain. Belt
      effects include decreased rectus femoris activity in patients and improved
      postural steadiness during locomotion. Pelvic belts may therefore be considered
      as a cost-effective and low-risk treatment of SIJ pain. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT02027038.

PMID- 26305793
TI  - Evaluating the A-Subunit of the Heat-Labile Toxin (LT) As an Immunogen and a
      Protective Antigen Against Enterotoxigenic Escherichia coli (ETEC).
AB  - Diarrheal illness contributes to malnutrition, stunted growth, impaired cognitive
      development, and high morbidity rates in children worldwide. Enterotoxigenic
      Escherichia coli (ETEC) is a major contributor to this diarrheal disease burden.
      ETEC cause disease in the small intestine by means of colonization factors and by
      production of a heat-labile enterotoxin (LT) and/or a small non-immunogenic heat
      stable enterotoxin (ST). Overall, the majority of ETEC produce both ST and LT. LT
      induces secretion via an enzymatically active A-subunit (LT-A) and a pentameric,
      cell-binding B-subunit (LT-B). The importance of anti-LT antibodies has been
      demonstrated in multiple clinical and epidemiological studies, and a number of
      potential ETEC vaccine candidates have included LT-B as an important immunogen.
      However, there is limited information about the potential contribution of LT-A to
      development of protective immunity. In the current study, we evaluate the immune
      response against the A-subunit of LT as well as the A-subunit's potential as a
      protective antigen when administered alone or in combination with the B-subunit
      of LT. We evaluated human sera from individuals challenged with a prototypic wild
      type ETEC strain as well as sera from individuals living in an ETEC endemic area
      for the presence of anti-LT, anti-LT-A and anti-LT-B antibodies. In both cases, a
      significant number of individuals intentionally or endemically infected with ETEC
      developed antibodies against both LT subunits. In addition, animals immunized
      with the recombinant proteins developed robust antibody responses that were able
      to neutralize the enterotoxic and cytotoxic effects of native LT by blocking
      binding and entry into cells (anti-LT-B) or the intracellular enzymatic activity
      of the toxin (anti-LT-A). Moreover, antibodies to both LT subunits acted
      synergistically to neutralize the holotoxin when combined. Taken together, these
      data support the inclusion of both LT-A and LT-B in prospective vaccines against
      ETEC. 

PMID- 26305794
TI  - Genomic Variants Revealed by Invariably Missing Genotypes in Nelore Cattle.
AB  - High density genotyping panels have been used in a wide range of applications.
      From population genetics to genome-wide association studies, this technology
      still offers the lowest cost and the most consistent solution for generating SNP
      data. However, in spite of the application, part of the generated data is always
      discarded from final datasets based on quality control criteria used to remove
      unreliable markers. Some discarded data consists of markers that failed to
      generate genotypes, labeled as missing genotypes. A subset of missing genotypes
      that occur in the whole population under study may be caused by technical issues
      but can also be explained by the presence of genomic variations that are in the
      vicinity of the assayed SNP and that prevent genotyping probes from annealing.
      The latter case may contain relevant information because these missing genotypes
      might be used to identify population-specific genomic variants. In order to
      assess which case is more prevalent, we used Illumina HD Bovine chip genotypes
      from 1,709 Nelore (Bos indicus) samples. We found 3,200 missing genotypes among
      the whole population. NGS re-sequencing data from 8 sires were used to verify the
      presence of genomic variations within their flanking regions in 81.56% of these
      missing genotypes. Furthermore, we discovered 3,300 novel SNPs/Indels, 31% of
      which are located in genes that may affect traits of importance for the genetic
      improvement of cattle production. 

PMID- 26305796
TI  - Identification of Distinct Tumor Subpopulations in Lung Adenocarcinoma via Single
      Cell RNA-seq.
AB  - Single-cell sequencing, which is used to detect clinically important tumor
      subpopulations, is necessary for understanding tumor heterogeneity. Here, we
      analyzed transcriptomic data obtained from 34 single cells from human lung
      adenocarcinoma (LADC) patient-derived xenografts (PDXs). To focus on the
      intrinsic transcriptomic signatures of these tumors, we filtered out genes that
      displayed extensive expression changes following xenografting and cell culture.
      Then, we performed clustering analysis using co-regulated gene modules rather
      than individual genes to minimize read drop-out errors associated with single
      cell sequencing. This combined approach revealed two distinct intra-tumoral
      subgroups that were primarily distinguished by the gene module G64. The G64
      module was predominantly composed of cell-cycle genes. E2F1 was found to be the
      transcription factor that most likely mediates the expression of the G64 module
      in single LADC cells. Interestingly, the G64 module also indicated inter-tumoral
      heterogeneity based on its association with patient survival and other clinical
      variables such as smoking status and tumor stage. Taken together, these results
      demonstrate the feasibility of single-cell RNA sequencing and the strength of our
      analytical pipeline for the identification of tumor subpopulations. 

PMID- 26305797
TI  - Structure Learning in Bayesian Sensorimotor Integration.
AB  - Previous studies have shown that sensorimotor processing can often be described
      by Bayesian learning, in particular the integration of prior and feedback
      information depending on its degree of reliability. Here we test the hypothesis
      that the integration process itself can be tuned to the statistical structure of
      the environment. We exposed human participants to a reaching task in a three
      dimensional virtual reality environment where we could displace the visual
      feedback of their hand position in a two dimensional plane. When introducing
      statistical structure between the two dimensions of the displacement, we found
      that over the course of several days participants adapted their feedback
      integration process in order to exploit this structure for performance
      improvement. In control experiments we found that this adaptation process
      critically depended on performance feedback and could not be induced by verbal
      instructions. Our results suggest that structural learning is an important meta
      learning component of Bayesian sensorimotor integration. 

PMID- 26305798
TI  - Endogenous Opioid-Masked Latent Pain Sensitization: Studies from Mouse to Human.
AB  - Following the resolution of a severe inflammatory injury in rodents,
      administration of mu-opioid receptor inverse agonists leads to reinstatement of
      pain hypersensitivity. The mechanisms underlying this form of latent pain
      sensitization (LS) likely contribute to the development of chronic pain, but LS
      has not yet been demonstrated in humans. Using a C57BL/6 mouse model of cutaneous
      mild heat injury (MHI) we demonstrated a dose-dependent reinstatement of pain
      sensitization, assessed as primary (P < 0.001) and secondary hyperalgesia (P <
      0.001) by naloxone (0.3-10 mg/kg), 168 hrs after the induction of MHI. Forward
      translating the dose data to a human MHI model (n = 12) we could show that LS
      does indeed occur after naloxone 2 mg/kg, 168 hrs after a MHI. Our previous
      unsuccessful efforts to demonstrate unmasking of LS in humans are thus likely
      explained by an insufficient naloxone dose (0.021 mg/kg). However, while LS was
      consistently demonstrated in 21/24 mice, LS was only seen in 4/12 subjects. This
      difference is likely due to selection bias since the C57BL/6 mouse strain
      exhibits markedly enhanced pain sensitivity in assays of acute thermal
      nociception. Future exploratory studies in humans should prioritize inclusion of
      "high-sensitizers" prone to develop LS and use post-surgical models to elucidate
      markers of vulnerability to chronic postsurgical pain. TRIAL REGISTRATION:
      EudraCT 2012-005663-27.

PMID- 26305799
TI  - Limitations of Mass Spectrometry-Based Peptidomic Approaches.
AB  - Mass spectrometry-based peptidomic approaches are powerful techniques to detect
      and identify the peptide content of biological samples. The present study
      investigated the limitations of peptidomic approaches using trimethylammonium
      butyrate isotopic tags to quantify relative peptide levels and Mascot searches to
      identify peptides. Data were combined from previous studies on human cell lines
      or mouse tissues. The combined databases contain 2155 unique peptides ranging in
      mass from 444 to 8765 Da, with the vast majority between 1 and 3 kDa. The amino
      acid composition of the identified peptides generally reflected the frequency in
      the Eukaryotic proteome with the exception of Cys, which was not present in any
      of the identified peptides in the free-SH form but was detected at low frequency
      as a disulfide with Cys residues, a disulfide with glutathione, or as S
      cyanocysteine. To test if the low detection rate of peptides smaller than 500 Da,
      larger than 3 kDa, or containing Cys was a limitation of the peptidomics
      procedure, tryptic peptides of known proteins were processed for peptidomics
      using the same approach used for human cell lines and mouse tissues. The
      identified tryptic peptides ranged from 516 to 2418 Da, whereas the theoretical
      digest ranged from 217 to 7559 Da. Peptides with Cys were rarely detected and, if
      present, the Cys was usually modified S-cyanocysteine. Additionally, peptides
      with mono- and di-iodo Tyr and His were identified. Taken together, there are
      limitations of peptidomic techniques, and awareness of these limitations is
      important to properly use and interpret results. Graphical Abstract ?. 

PMID- 26305800
TI  - Efficient Generation of Myostatin Knock-Out Sheep Using CRISPR/Cas9 Technology
      and Microinjection into Zygotes.
AB  - While CRISPR/Cas9 technology has proven to be a valuable system to generate gene
      targeted modified animals in several species, this tool has been scarcely
      reported in farm animals. Myostatin is encoded by MSTN gene involved in the
      inhibition of muscle differentiation and growth. We determined the efficiency of
      the CRISPR/Cas9 system to edit MSTN in sheep and generate knock-out (KO) animals
      with the aim to promote muscle development and body growth. We generated
      CRISPR/Cas9 mRNAs specific for ovine MSTN and microinjected them into the
      cytoplasm of ovine zygotes. When embryo development of CRISPR/Cas9 microinjected
      zygotes (n = 216) was compared with buffer injected embryos (n = 183) and non
      microinjected embryos (n = 173), cleavage rate was lower for both microinjected
      groups (P<0.05) and neither was affected by CRISPR/Cas9 content in the injected
      medium. Embryo development to blastocyst was not affected by microinjection and
      was similar among the experimental groups. From 20 embryos analyzed by Sanger
      sequencing, ten were mutant (heterozygous or mosaic; 50% efficiency). To obtain
      live MSTN KO lambs, 53 blastocysts produced after zygote CRISPR/Cas9
      microinjection were transferred to 29 recipient females resulting in 65.5%
      (19/29) of pregnant ewes and 41.5% (22/53) of newborns. From 22 born lambs
      analyzed by T7EI and Sanger sequencing, ten showed indel mutations at MSTN gene.
      Eight showed mutations in both alleles and five of them were homozygous for
      indels generating out-of frame mutations that resulted in premature stop codons.
      Western blot analysis of homozygous KO founders confirmed the absence of
      myostatin, showing heavier body weight than wild type counterparts. In
      conclusion, our results demonstrate that CRISPR/Cas9 system was a very efficient
      tool to generate gene KO sheep. This technology is quick and easy to perform and
      less expensive than previous techniques, and can be applied to obtain genetically
      modified animal models of interest for biomedicine and livestock. 

PMID- 26305802
TI  - Boron and Nitrogen Codoped Carbon Layers of LiFePO4 Improve the High-Rate
      Electrochemical Performance for Lithium Ion Batteries.
AB  - An evolutionary composite of LiFePO4 with nitrogen and boron codoped carbon
      layers was prepared by processing hydrothermal-synthesized LiFePO4. This novel
      codoping method is successfully applied to LiFePO4 for commercial use, and it
      achieved excellent electrochemical performance. The electrochemical performance
      can be improved through single nitrogen doping (LiFePO4/C-N) or boron doping
      (LiFePO4/C-B). When modifying the LiFePO4/C-B with nitrogen (to synthesis
      LiFePO4/C-B+N) the undesired nonconducting N-B configurations (190.1 and 397.9
      eV) are generated. This decreases the electronic conductivity from 2.56*10(-2) to
      1.30*10(-2) S cm(-1) resulting in weak electrochemical performance. Nevertheless,
      using the opposite order to decorate LiFePO4/C-N with boron (to obtain LiFePO4/C
      N+B) not only eliminates the nonconducting N-B impurity, but also promotes the
      conductive C-N (398.3, 400.3, and 401.1 eV) and C-B (189.5 eV) configurations
      this markedly improves the electronic conductivity to 1.36*10(-1) S cm(-1).
      Meanwhile the positive doping strategy leads to synergistic electrochemical
      activity distinctly compared with single N- or B-doped materials (even much
      better than their sum capacity at 20 C). Moreover, due to the electron and hole
      type carriers donated by nitrogen and boron atoms, the N+B codoped carbon coating
      tremendously enhances the electrochemical property: at the rate of 20 C, the
      codoped sample can elevate the discharge capacity of LFP/C from 101.1 mAh g(-1)
      to 121.6 mAh g(-1), and the codoped product based on commercial LiFePO4/C shows a
      discharge capacity of 78.4 mAh g(-1) rather than 48.1 mAh g(-1). Nevertheless,
      the B+N codoped sample decreases the discharge capacity of LFP/C from 101.1 mAh
      g(-1) to 95.4 mAh g(-1), while the commercial LFP/C changes from 48.1 mAh g(-1)
      to 40.6 mAh g(-1).

PMID- 26305801
TI  - In silico tumor control induced via alternating immunostimulating and
      immunosuppressive phases.
AB  - Despite recent advances in the field of Oncoimmunology, the success potential of
      immunomodulatory therapies against cancer remains to be elucidated. One of the
      reasons is the lack of understanding on the complex interplay between tumor
      growth dynamics and the associated immune system responses. Toward this goal, we
      consider a mathematical model of vascularized tumor growth and the corresponding
      effector cell recruitment dynamics. Bifurcation analysis allows for the
      exploration of model's dynamic behavior and the determination of these parameter
      regimes that result in immune-mediated tumor control. In this work, we focus on a
      particular tumor evasion regime that involves tumor and effector cell
      concentration oscillations of slowly increasing and decreasing amplitude,
      respectively. Considering a temporal multiscale analysis, we derive an
      analytically tractable mapping of model solutions onto a weakly negatively damped
      harmonic oscillator. Based on our analysis, we propose a theory-driven
      intervention strategy involving immunostimulating and immunosuppressive phases to
      induce long-term tumor control. 

PMID- 26305803
TI  - Identification of the Lomofungin Biosynthesis Gene Cluster and Associated Flavin
      Dependent Monooxygenase Gene in Streptomyces lomondensis S015.
AB  - Streptomyces lomondensis S015 synthesizes the broad-spectrum phenazine antibiotic
      lomofungin. Whole genome sequencing of this strain revealed a genomic locus
      consisting of 23 open reading frames that includes the core phenazine
      biosynthesis gene cluster lphzGFEDCB. lomo10, encoding a putative flavin
      dependent monooxygenase, was also identified in this locus. Inactivation of
      lomo10 by in-frame partial deletion resulted in the biosynthesis of a new
      phenazine metabolite, 1-carbomethoxy-6-formyl-4,9-dihydroxy-phenazine, along with
      the absence of lomofungin. This result suggests that lomo10 is responsible for
      the hydroxylation of lomofungin at its C-7 position. This is the first
      description of a phenazine hydroxylation gene in Streptomyces, and the results of
      this study lay the foundation for further investigation of phenazine metabolite
      biosynthesis in Streptomyces. 

PMID- 26305805
TI  - A Reversible Photoacid Functioning in PBS Buffer under Visible Light.
AB  - A metastable-state photoacid that can reversibly release a proton in PBS buffer
      (pH = 7.4) under visible light is reported. The design is based on the dual acid
      base property and tautomerization of indazole. The quantum yield was as high as
      0.73, and moderate light intensity (10(2) MUmol.m(2).s(-1)) is sufficient for the
      photoreaction. Reversible pH change of 1.7 units was demonstrated using a 0.1 mM
      aqueous solution. This type of photoacid is promising for control of proton
      transfer processes in physiological conditions and may find applications in
      biomedical areas. 

PMID- 26305804
TI  - Triphilic Ionic-Liquid Mixtures: Fluorinated and Non-fluorinated Aprotic Ionic
      Liquid Mixtures.
AB  - We present here the possibility of forming triphilic mixtures from alkyl- and
      fluoroalkylimidazolium ionic liquids, thus, macroscopically homogeneous mixtures
      for which instead of the often observed two domains-polar and nonpolar-three
      stable microphases are present: polar, lipophilic, and fluorous ones. The
      fluorinated side chains of the cations indeed self-associate and form domains
      that are segregated from those of the polar and alkyl domains. To enable
      miscibility, despite the generally preferred macroscopic separation between
      fluorous and alkyl moieties, the importance of strong hydrogen bonding is shown.
      As the long-range structure in the alkyl and fluoroalkyl domains is dependent on
      the composition of the liquid, we propose that the heterogeneous, triphilic
      structure can be easily tuned by the molar ratio of the components. We believe
      that further development may allow the design of switchable, smart liquids that
      change their properties in a predictable way according to their composition or
      even their environment. 

PMID- 26305806
TI  - Acytota - associated kingdom of neglected life.
AB  - There is a huge variety of RNA- and DNA-containing entities that multiply within
      and propagate between cells across all kingdoms of life, having no cells of their
      own. Apart from cellular organisms, these entities (viroids, plasmids, mobile
      elements and viruses among others) are the only ones with distinct genetic
      identities but which are not included in any traditional tree of life. We suggest
      to introduce or, rather, revive the distinct category of acellular organisms,
      Acytota, as an additional, undeservedly ignored full-fledged kingdom of life.
      Acytota are indispensable players in cellular life and its evolution. The six
      traditional kingdoms (Cytota) and Acytota together complete the classification of
      the biological world (Biota), leaving nothing beyond. 

PMID- 26305807
TI  - Sequence and organization of the complete mitogenome of a Siberian stone loach,
      Barbatula toni (Dybowsky, 1869) (Cypriniformes: Balitoridae).
AB  - In this study, we determined the complete mitogenome sequence of Siberian stone
      loach, Barbatula toni (Dybowsky, 1869). The total length of mitogenome is 16 623
      bp, which consists of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and 1
      control region (D-loop). The genome organization and gene order were identical to
      that of the typical vertebrates. The control region harbors conserved sequence
      blocks (CSB-D, E, F, CSB-1, CBS-2 and CBS-3) and TA-nucleotide microsatellite
      repeats in its 3' end. The complete mitogenome may provide important molecular
      data for further phylogenetic analyses for higher taxa of teleost fishes,
      especially for the fishes in order Cypriniformes.

PMID- 26305808
TI  - Mean frequency and relative fluorescence intensity measurement of gamma-H2AX foci
      dose response in PBL exposed to gamma-irradiation: An inter- and intra-laboratory
      comparison and its relevance for radiation triage.
AB  - Measurement of gamma-H2AX protein changes in the peripheral blood lymphocytes
      (PBL) of individuals exposed to ionizing radiation is a simple, sensitive, and
      rapid assay for radiation triage and early marker of dose estimation. The
      qualitative and quantitative measurements of the protein changes were examined
      using flow cytometry and microscopy. Whole blood and isolated lymphocytes were
      exposed in vitro between 0.1 and 5 Gy doses of (60) Co gamma-radiation at a dose
      rate of 1 Gy/min. Radiation induced gamma-H2AX foci frequency (n = 3) and
      relative fluorescence intensity (n = 7) in PBL was measured at 0.5 and 2 hrs
      postexposure. The observed dose response for gamma-H2AX foci frequency at both
      time points, for whole blood and isolated lymphocytes did not show any
      significant (P > 0.05) differences. However, when compared with gamma-H2AX foci
      frequency scored manually (microscopy), the semiautomated analysis (captured
      images) showed a better correlation (r(2) = 0.918) than that obtained with
      automated (Metafer) scoring (r(2) = 0.690). It is noteworthy to mention that, the
      gamma-H2AX foci frequency quantified using microscopy showed a dose dependent
      increase up to 2 Gy and the relative fluorescence intensity (RFI) measured with
      flow cytometry revealed an increase up to 5 Gy in the PBL exposed in vitro.
      Moreover, a better correlation was observed between the gamma-H2AX foci frequency
      obtained by manual scoring and RFI (r(2) = 0.910). Kinetic studies showed that
      the gamma-H2AX foci remain more or less unchanged up to 4 hrs and reduces
      gradually over 48 hrs of postexposure at 37 degrees C. Further, inter and intra
      laboratory comparisons showed consistency in the scoring of gamma-H2AX foci
      frequency by manual and semiautomated scoring. The overall results suggest that
      measurement of gamma-H2AX (microscopy and flow cytometry) should be employed
      within 4 to 6 hrs for a reliable dosimetry either by sharing the work load
      between the laboratories or investing more manpower; however, triage can be
      possible even up to 48 hrs of postirradiation.

PMID- 26305809
TI  - Prognostic factors for the feasibility of chemotherapy and the Geriatric
      Prognostic Index (GPI) as risk profile for mortality before chemotherapy in the
      elderly.
AB  - BACKGROUND: Comprehensive geriatric assessment (CGA) is a multidimensional method
      to detect frailty in elderly patients. Time saving could be accomplished by
      identifying those individual items that classify elderly cancer patients at risk
      for feasibility of chemotherapy and for mortality. MATERIAL AND METHODS: Patients
      older than 70 years of age were assessed before the first chemotherapy
      administration. GA consisted of the Mini Nutritional Assessment (MNA), Informant
      Questionnaire on Cognitive Decline in the Elderly (IQCODE), Groningen Frailty
      Indicator (GFI) and Mini Mental State Examination (MMSE). Predictive individual
      items for feasibility of chemotherapy and mortality were entered in the
      multivariable logistic regression and Cox-regression models, and a three-item sum
      scale was constructed: the Geriatric Prognostic Index (GPI). RESULTS: The 494
      patients had a median age of 75 years (range 70-92 years). The majority of the
      patients had malignancies of the digestive tract (41.7%) followed by
      hematological tumors (22.3%). Three items of the MNA ('psychological distress or
      acute disease in the past three months', 'neuropsychological problems' and 'using
      > 3 prescript drugs') independently predicted for feasibility of chemotherapy.
      Two items of the MNA and one of the GFI ('declining food intake in past 3
      months', 'using > 3 prescript drugs', and 'dependence in shopping') independently
      predicted for mortality. In comparison with patients without any positive item on
      the three-item GPI, patients with one, two or three positive items had hazard
      ratios (HRs) of 1.58, 2.32, and 5.58, respectively (all p < 0.001). CONCLUSIONS:
      With only three items of the MNA, feasibility of chemotherapy can be predicted.
      The three-item GPI may help to identify elderly cancer patients at elevated risk
      for mortality.

PMID- 26305810
TI  - The JCPYV DNA load inversely correlates with the viral microrna expression in
      blood and cerebrospinal fluid of patients at risk of PML.
AB  - BACKGROUND: In light of their regulatory role, changes in the expression of
      Polyomavirus JC (JCPyV) microRNAs may be relevant for virus reactivation and the
      development of progressive multifocal leukoencephalopathy (PML). OBJECTIVES: To
      investigate the presence of JCPyV-DNA and JCPyV microRNA expression in clinical
      specimens of patients at risk for PML. STUDY DESIGN: The JCPyV-DNA and microRNA
      status was assessed in peripheral blood mononuclear cells (PBMCs) and plasma from
      100 HIV patients, in serum and cerebrospinal fluid (CSF) from 14 HIV PML patients
      and in PBMCs and plasma from 50 healthy controls using Multiplex real-time PCR
      and JCPyV miRNA-J1-3p and -5p stem-loop RT-PCR. The JCPyV-DNA microRNA-expressing
      region was also sequenced. RESULTS: A positive JCPyV-DNA status was more
      prevalent in HIV patients (67%, 67/100) compared to healthy controls (18%, 9/50).
      Among these, 46% and 42% of the HIV patients and 18% and 0% of the healthy
      controls were positive based on PBMC and plasma determinations, respectively.
      PBMC JCPyV microRNA positivity was observed in 22 out of 46 (48%) JCPyV+ HIV
      patients and in 3 out of 9 (33%) JCPyV+ healthy controls. Moreover, JCPyV
      microRNAs in exosomes were found in 6 out of 100 (6%) HIV plasma samples, in 12
      out of 50 (24%) healthy samples, in 6 out of 14 (43%) serum samples, and in 3 out
      of 5 (60%) HIV PML CSF samples. Of note, the JCPyV-DNA load was inversely
      correlated with expression of the viral microRNA. The JCPyV microRNA genomic
      expression region showed a different combination of three mutations. CONCLUSIONS:
      The low levels of JCPyV microRNA expression in HIV patients with high JCPyV-DNA
      prevalence observed in this study highlight the potential clinical relevance of
      JCPyV microRNAs in PML risk assessment.

PMID- 26305811
TI  - Molecular epidemiological analysis of Saffold cardiovirus genotype 3 from upper
      respiratory infection patients in Taiwan.
AB  - BACKGROUND: Saffold cardiovirus (SAFV) belongs to the Cardiovirus genus of
      Picornaviridae family, and may be a relevant new human pathogen; Thus far, eleven
      genotypes have been identified. The SAFV type 3 (SAFV-3) is thought to be the
      major genotype and is detected relatively frequently in children with acute
      gastroenteritis and respiratory illness. The epidemiology and pathogenicity of
      SAFV-3 remain unclear. OBJECTIVES: To investigate the genomic and epidemiologic
      profiles of SAFV-3 infection in Taiwan. STUDY DESIGN: Virus was detected in
      respiratory samples from children suffering for URI. SAFV-3 isolates were
      detected by isolation on cell culture and IF assay. The molecular typing was
      performed by RT-PCR and was sequenced to compare with reference strains available
      in the NCBI GeneBank. Serum samples were collected from 2005 to 2013 in Taiwan
      for seroprevalence investigation. RESULTS: A total of 226 specimens collected
      from children with URIs, 22 (9.73%) were positive for SAFV-3. The majority of
      SAFV-3 infections were found in children less than 6 years of age (14 of 22,
      63.6%). Genetic analysis of VP1 coding region of Taiwanese isolates shown an 83.2
      97.7% difference from other available SAFV-3 sequences in NCBI GenBank.
      Phylogenetic analysis revealed there is three genetic groups of SAFV-3 co
      circulated in Taiwan during the study period. In addition, seroprevalence
      investigation results indicated that SAFV-3 infection occurs early in life and
      43.7-77.8% of children aged between 6 months to 9 years old, had neutralizing
      antibodies against SAFV-3. CONCLUSION: SAFV-3 may have circulated in Taiwan for
      some time and it appears to be one of the etiological agents responsible for URIs
      in children.

PMID- 26305812
TI  - Mortality and fatality due to Chikungunya virus infection in Colombia.

PMID- 26305813
TI  - Living poultry markets in rural area: Human infection with H7N9 virus re-emerges
      in Zhejiang Province, China, in winter 2014.
AB  - BACKGROUND: Avian influenza A H7N9 virus, previously undetected in humans, has
      caused infections in many areas in China since February 2013. Here we report the
      re-emergence of a case of H7N9 in rural Jiaxing city, Zhejiang Province, in the
      winter of 2014. OBJECTIVES: To understand (1) the clinical syndrome,
      epidemiological and virological characteristics of this case; (2) the importance
      of controlling live poultry markets (LPMs) in rural areas. STUDY DESIGN: There is
      one patient and 16 contacts, including 4 family members living in the same
      household, and 12 medical personnel. Pharyngeal swabs and serum samples were
      collected from the patient and her contacts. Environment samples were also
      obtained from the local LPMs. We conducted detailed clinical and epidemiological
      investigations and laboratory work, including viral RNA extraction, RT-PCR
      detection and sequencing. Characteristic and phylogenetic analyses were performed
      using the obtained sequences. RESULTS: H7N9s were detected in environmental
      samples collected in LPMs in Jiaxing, Zhejiang. Unknown mutations were discovered
      in amino acids in the sample from the patient. The strain from the patient was in
      a clade different from isolates obtained in 2013 in phylogenetic trees of HA, NA
      and PB2. CONCLUSIONS: A severe case of H7N9 was identified in early winter, 2014.
      Epidemiological and clinical tests were consistent with patterns reported
      previously, while laboratory findings showed the virus to be different. Live
      poultry markets in rural Zhejiang Province are in need of closer supervision and
      enhanced management.

PMID- 26305814
TI  - Hepatitis E virus infection: An underdiagnosed infection in transplant patients
      in Southern Africa?

PMID- 26305815
TI  - Surveillance of norovirus in Portugal and the emergence of the Sydney variant,
      2011-2013.
AB  - This report presents the results of the national surveillance system of diarrhea
      etiology of the National Institute of Health of Portugal concerning norovirus
      (NoV) during a two-year period, May 2011-2013. Of the total 580 stool samples
      collected from patients hospitalized for acute diarrhea in 13 Hospitals of
      Portugal, 67 (11.6%) tested positive for NoV. From May 2011 to March 2012 the
      GII.4 variant New Orleans 2009 was the most predominant strain having been
      replaced by the new GII.4 variant Sydney 2012 since then till the end of the
      survey. To our knowledge this is the first study showing the circulation of GII.4
      as the norovirus strain most commonly associated to gastroenteritis and the first
      to report the replacement of GII.4 New Orleans by GII.4 Sydney 2012 variant in
      Portugal. 

PMID- 26305816
TI  - Fourteen types of co-circulating recombinant enterovirus were associated with
      hand, foot, and mouth disease in children from Wenzhou, China.
AB  - BACKGROUND: Although hand, foot, and mouth disease (HFMD) is a major public
      concern in China, the prevalence and clinical symptoms associated with the
      different agents of HFMD in this country remain poorly understood. OBJECTIVES: We
      investigated the clinical and molecular characteristics of enteroviruses in
      patients with HFMD from Wenzhou, China. STUDY DESIGN: Patients with laboratory
      confirmed HFMD admitted to the Yuying Children's Hospital in Wenzhou, China
      during 2013 were included in this study. Viral RNA sequences were amplified using
      RT-PCR, determined by sequencing, and compared by phylogenetic analysis. RESULTS:
      A total of 955 clinically diagnosed HFMD cases were determined using PCR, with
      whole viral genomes obtained for each enterovirus type. 14 types of enterovirus
      belonging to two viral species were identified. Notably, Coxsackievirus A6 (CV
      A6) was the most common species detected (77.8%), followed by EV-A71 (8.2%) and
      CV-A10 (8.1%). Phylogenetic analysis revealed multiple independent introductions
      of these viruses into Wenzhou. In addition, the enterovirus observed in Wenzhou
      had a recombinant history, with two or three recombination breakpoints. Although
      the illness associated with CV-A6 was milder than that of EV-A71, CV-A6 infection
      caused more widespread rash, larger blisters, and subsequent skin peeling and/or
      nail shedding. CONCLUSION: Our study revealed the co-circulation of 14 types of
      enteroviruses in a single location - Wenzhou, China - with CV-A6 virus the
      predominant agent of HFMD. This work highlights the need to perform larger-scale
      surveillance to fully understand the epidemiology of enteroviruses in China and
      the wider Asia-Pacific region.

PMID- 26305817
TI  - Hepatitis E virus seroprevalence in three hyperendemic areas: Nepal, Bangladesh
      and southwest France.
AB  - BACKGROUND: Hepatitis E causes a significant burden of disease in developing
      countries and has recently been increasingly recognized in developed countries.
      Comparing population anti-hepatitis E virus (HEV) seroprevalence across
      populations has been difficult. OBJECTIVES: The aim of this study was to compare
      the anti-HEV IgG seroprevalence in both adults and children in three hyper
      endemic areas (Nepal, Bangladesh and southwest France) using a sensitive,
      commercial anti-HEV IgG assay. STUDY DESIGN: Serum or plasma from adults and
      children in Nepal (n=498), Bangladesh (n=1,009) and Southwest France (n=1031)
      were tested for anti-HEV IgG using the Wantai assay. RESULTS: After age
      standardization, anti-HEV IgG seroprevalence was 47.1%, 49.8% and 34.0% in Nepal,
      Bangladesh and southwest France, respectively. There was no difference in
      seroprevalence by gender in any of the countries. A paucity of infections in
      children 1-10 years-old was consistently observed (less than 15%) at all 3
      locations. CONCLUSIONS: Surprisingly similar high rates of anti-HEV antibodies
      were detected using a common, sensitive assay. Despite differences in the
      epidemiology and circulating genotype of HEV in Nepal, Bangladesh and southwest
      France, this study found more similarities in population seroprevalence than
      expected.

PMID- 26305818
TI  - Natural prevalence of resistance-associated variants in hepatitis C virus NS5A in
      genotype 3a-infected people who inject drugs in Germany.
AB  - BACKGROUND: People who inject drugs (PWID) are the most important risk group for
      incident Hepatitis C virus (HCV) infection. In PWID in Europe HCV genotype 3a is
      highly prevalent. Unfortunately, many of the recently developed directly acting
      antiviral drugs against HCV (DAAs) are suboptimal for treatment of this genotype.
      Detection of resistance-associated variants (RAV) in genotype 3a may help to
      optimize treatment decisions, however, robust protocols for amplification and
      sequencing of HCV NS5A as an important target for treatment of genotype 3a are
      currently lacking. OBJECTIVES: The aim of this study was to establish a protocol
      for sequencing of HCV NS5A in genotype 3a and to determine the frequency of RAVs
      in treatment-naive PWID living in Germany. STUDY DESIGN: The full NS5A region was
      amplified and sequenced from 110 HCV genotype 3a infected PWID using an in-house
      PCR protocol. RESULTS: With the established protocol the complete NS5A region was
      successfully amplified and sequenced from 110 out of 112 (98.2%) genotype 3a
      infected PWID. Phylogenetic analysis of sequences from PWID together with
      unrelated genotype 3a sequences from a public database showed a scattered
      distribution without geographic clustering. Viral polymorphisms A30K and Y93H
      known to confer resistance in a GT3a replication model were present in 8 subjects
      (7.2%). CONCLUSIONS: A protocol for amplification of nearly all GT3a samples was
      successfully established. Substitutions conferring resistance to NS5A inhibitors
      were detected in a few treatment-naive PWID.

PMID- 26305819
TI  - What assay is optimal for the diagnosis of measles virus infection? An evaluation
      of the performance of a measles virus real-time reverse transcriptase PCR using
      the Cepheid SmartCycler((r)) and antigen detection by immunofluorescence.
AB  - BACKGROUND: Despite the World Health Organization (WHO)-reported elimination of
      measles in Australia, importation of cases especially in travellers from Asia
      continues in Sydney, Australia's largest city. Laboratory confirmation supports
      clinico-epidemiological evidence of measles virus infection, and is needed to
      establish elimination. OBJECTIVES: To evaluate the performance of a random access
      real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay using
      the moderate complexity SmartCycler((r)) platform, and measles antigen detection
      by immunofluorescence (IFA), for the detection of measles virus in patient
      samples. STUDY DESIGN: One hundred samples comprising nose and throat swabs,
      nasopharyngeal aspirates and urine, collected from patients with suspected
      measles were tested in parallel using IFA and nucleic acid testing using the
      SmartCycler((r)) and LightCycler((r)) RT-PCR platforms. The LightCycler((r)) RT
      PCR was used as the reference assay against which the SmartCycler((r)) RT-PCR and
      IFA were compared. RESULTS: Using the LightCycler((r)) RT-PCR, measles virus was
      detected in 35 clinical samples. There was 100% concordance between the results
      of the SmartCycler((r)) and the LightCycler((r))-based RT-PCR. Measles genotypes
      detected included B3, D8, and D9. Testing urine in addition to NTS did not
      improve diagnostic yield. In contrast, the sensitivity and specificity of IFA
      compared to the reference LightCycler((r)) RT-PCR was 34.3% and 96.7%,
      respectively. CONCLUSION: The performance of the SmartCycler((r)) is comparable
      to the LightCycler((r)) for the detection of measles virus. However, IFA had poor
      sensitivity and should not be used to confirm measles virus infection where
      nucleic acid testing is available.

PMID- 26305820
TI  - The predictive value of human papillomavirus testing for the outcome of patients
      conservatively treated for stage IA squamous cell cervical carcinoma.
AB  - BACKGROUND: Although it is hypothesised that human papillomavirus (HPV) testing
      may have a role in surveillance of patients conservatively treated for stage IA
      squamous cell cervical carcinoma, research on this topic has been minimal.
      OBJECTIVES: To determine: (1) the changes in HPV test result from treatment
      onward; (2) the time to viral clearance; and (3) the negative predictive value
      (NPV) and positive predictive value (PPV) of HPV test result for the detection of
      CIN2 or worse (CIN2+) during follow-up. STUDY DESIGN: In a multicentre
      retrospective follow-up study of a consecutive series (1997-2009) of 91 patients,
      longitudinal outcome measures were estimated as cumulative probabilities using
      the Kaplan-Meier method. RESULTS: For patients testing HPV-positive at the first
      follow-up visit (n=44), the probability of change to negative rose from 0 to 0.78
      between 7 and 21 months after treatment. For HPV-negative patients (n=47), the
      probability of change to positive rose to 0.13 between 9 and 26 months. After a
      median follow-up of 50 months (range, 2-80), the NPV for CIN2+ was 1.00. The PPV
      was 0.60 (95% confidence interval, 0.43-0.77) after 26 months. The median time to
      detection was 5 months. CONCLUSIONS: If adequately confirmed, these findings
      would indicate that HPV testing is capable to identify the patients who have had
      their lesions fully removed, and would make it possible to focus follow-up
      efforts on a subset of patients at high risk of residual or progressive disease.

PMID- 26305821
TI  - Carriage of herpes simplex virus and human papillomavirus in oral mucosa is rare
      in young women: A long-term prospective follow-up.
AB  - BACKGROUND: Following the primary oral infection, herpes simplex virus (HSV)
      establishes latency in the ganglia of sensory neurons. Episodically induced by
      stress, HSV is able to cause recurrent infection at the primary infection site,
      accompanied by virus shedding. The oral shedding of HSV contributes to mother
      child-transmission of HSV. Human papillomavirus (HPV) is associated with oral
      malignancies, and its interaction with oral HSV should be studied further.
      OBJECTIVES: To analyze the prevalence of HSV-1 and HSV-2-infection in oral
      mucosal scrapings of women during and after pregnancy and to elucidate the
      prevalence of HPV and HSV-co-carriage in oral mucosa. STUDY DESIGN: A
      longitudinal cohort study of 304 mothers in the Finnish Family HPV study followed
      up for 6 years after pregnancy, with 7 serial samplings. Mothers' oral brush
      samples were analyzed with quantitative PCR for HSV-1 and -2 DNA and the findings
      were compared with their HPV DNA status. RESULTS: Altogether, 2.2% of all 1873
      collected epithelial brush samples were HSV-1 DNA positive, while none tested HSV
      2 DNA positive. Of the 304 mothers, 11.8% were HSV-1 DNA positive at least once.
      Most of the women who tested HSV-1 DNA positive before delivery remained HSV-1
      DNA positive also after pregnancy. HSV-1 positive women were almost invariably
      HPV-negative; only four (0.2%) samples were detected with HSV-HPV co-carriage.
      CONCLUSIONS: This is the first prospective follow-up study on oral HSV shedding
      and its association with coexistent HPV, analyzed in the same oral mucosal
      scrapings. HSV and HPV co-carriage is rare in oral mucosa of healthy young
      mothers.

PMID- 26305822
TI  - Ultra-deep sequencing provides insights into the virology of hepatitis C super
      infections in a case of three sequential infections with different genotypes.
AB  - The current epidemic of Hepatitis C infection in HIV-positive men who have sex
      with men is associated with increasing use of recreational drugs. Multiple HCV
      infections have been reported in haemophiliacs and intravenous drug users. Using
      ultra-deep sequencing analysis, we present the case of an HIV-positive MSM with
      evidence of three sequential HCV infections, each occurring during the acute
      phase of the preceding infection, following risk exposures. We observed rapid
      replacement of the original strain by the incoming genotype at subsequent time
      points. The impact of HCV super-infection remains unclear and UDS may provide new
      insights. 

PMID- 26305823
TI  - The APOBEC3B deletion polymorphism is associated with prevalence of hepatitis B
      virus, hepatitis C virus, Torque Teno virus, and Toxoplasma gondii co-infection
      among HIV-infected individuals.
AB  - BACKGROUND: Data regarding the influence of the APOBEC3B deletion on infectious
      diseases remain limited and shown discrepancies. OBJECTIVES: To characterize the
      APOBEC3B deletion polymorphism status and its association with prevalence of co
      infection with blood-borne pathogens in Indonesian HIV-infected individuals.
      MATERIALS AND METHODS: A total of 597 HIV-positive blood samples were tested for
      the hepatitis B virus (HBV), hepatitis C virus (HCV), Torque Teno virus (TTV), GB
      virus-C (GBV-C), and Toxoplasma gondii. Nucleic acid was extracted from plasma
      samples and used for the molecular detection of HIV RNA, HBV DNA, HCV RNA, TTV
      DNA, and GBV-C RNA, whereas HBsAg, anti-HCV, IgM and IgG anti-T. gondii were
      detected through serological testing. The APOBEC3B deletion polymorphism was
      genotyped by polymerase chain reaction (PCR). RESULTS: The deletion genotype was
      associated with HCV viremia (p<0.001) as well as elevated IgG anti-T. gondii
      (adjusted OR [aOR]=3.4). The deletion genotype was also associated with decreased
      levels of HBsAg (aOR=0.03), and anti-HCV (aOR=0.1). D/D was frequently found in
      HIV-infected individuals with CD4+T cells<14% (aOR=5.8). The intact genotype was
      associated with a reduced likelihood of a CD4+T cell count<200 cells/MUL
      (aOR=0.2) but a higher prevalence of TTV co-infection (aOR=8.6). CONCLUSIONS: The
      APOBEC3B deletion polymorphism was found to be associated with HBV, HCV, TTV, and
      T. gondii co-infection in Indonesian HIV-infected individuals.

PMID- 26305824
TI  - Performance of the Alere i influenza A&B assay and mariPOC test for the rapid
      detection of influenza A and B viruses.
AB  - BACKGROUND: Timely detection of influenza viruses is required to facilitate
      infection control measures and appropriate patient management. The AlereTM i
      Influenza A&B assay for detection of viral RNA and multianalyte mariPOC((r)) test
      for detection of viral antigens enable rapid detection of influenza viruses with
      little hands-on time. OBJECTIVES: To evaluate the performance of the Alere i
      Influenza A&B assay and the mariPOC test in comparison to the Xpert((r)) Flu A/B
      assay and laboratory-developed real-time reverse transcription-polymerase chain
      reaction. STUDY DESIGN: A total of 140 and 108 nasopharyngeal specimens were
      analysed for evaluation of the Alere i and mariPOC, respectively. RESULTS: The
      sensitivity and specificity of the Alere i Influenza A&B assay for detection of
      influenza A virus was 80.0% and 98.1%, and for influenza B virus 45.2% and 98.2%,
      respectively. For the mariPOC test, a sensitivity and specificity of 53.1% and
      98.7%, respectively, for detection of influenza A virus was achieved.
      CONCLUSIONS: The mariPOC test proved insensitive for detection of influenza A
      virus and therefore unsuitable for individual patient diagnosis without
      confirmatory testing. In contrast, the Alere i Influenza A&B assay was reasonably
      sensitive and specific for detection of influenza A and B virus, although
      decreased detection of specimens with low viral load was observed particularly
      for detection of influenza B virus. Taken together with its rapidity and ease of
      use, the Alere i influenza A&B assay is a welcome alternative to
      immunochromatographic rapid influenza detection tests and may provide timely
      results that enable appropriate patient care and management of patient flow
      during high-prevalence seasons.

PMID- 26305825
TI  - Severe enterovirus 68 respiratory illness in children requiring intensive care
      management.
AB  - BACKGROUND: Enterovirus 68 (EV-D68) causes acute respiratory tract illness in
      epidemic cycles, most recently in Fall 2014, but clinical characteristics of
      severe disease are not well reported. OBJECTIVES: Children with EV-D68 severe
      respiratory disease requiring pediatric intensive care unit (PICU) management
      were compared with children with severe respiratory disease from other
      enteroviruses/rhinoviruses. STUDY DESIGN: A retrospective review was performed of
      all children admitted to Children's Mercy Hospital PICU from August 1-September
      15, 2014 with positive PCR testing for enterovirus/rhinovirus. Specimens were
      subsequently tested for the presence of EV-D68. We evaluated baseline
      characteristics, symptomatology, lab values, therapeutics, and outcomes of
      children with EV-D68 viral infection compared with enterovirus/rhinovirus
      positive, EV-D68-negative children. RESULTS: A total of 86 children with positive
      enterovirus/rhinovirus testing associated with respiratory symptoms were admitted
      to the PICU. Children with EV-D68 were older than their EV-D68-negative
      counterparts (7.1 vs. 3.5 years, P=0.01). They were more likely to have a history
      of asthma or recurrent wheeze (68% vs. 42%, P=0.03) and to present with cough
      (90% vs. 63%, P=0.009). EV-D68 children were significantly more likely to receive
      albuterol (95% vs. 79%, P=0.04), magnesium (75% vs. 42%, P=0.004), and
      aminophylline (25% vs. 4%, P=0.03). Other adjunctive medications used in EV-D68
      children included corticosteroids, epinephrine, and heliox; 44% of EV-D68
      positive children required non-invasive ventilatory support. CONCLUSIONS: EV-D68
      causes severe disease in the pediatric population, particularly in children with
      asthma and recurrent wheeze; children may require multiple adjunctive respiratory
      therapies.

PMID- 26305826
TI  - Unique clinical and imaging findings in a first ever documented PCR positive
      rabies survival patient: A case report.
AB  - BACKGROUND: Rabies is fatal encephalitis which is a major public health problem
      in Asian and African countries. Till date, only 12 cases have been reported who
      have survived after rabies. CASE REPORT: In this communication we report a
      patient who is unique as the first documented long term rabies survivor with PCR
      positivity even after 41/2 years of illness. Child sustained dog bite following
      which he received adequate prophylaxis. Within two weeks, child developed
      encephalopathy requiring evaluation. Child continues to have persistent myoclonic
      jerks, seizures, is dependent on all activities with severe neurological
      deficits. Nested reverse transcriptase PCR (RT-PCR) specific for rabies
      nucleoprotein gene in CSF and nuchal skin biopsy were positive for rabies viral
      RNA. The nuchal skin biopsy was also positive for rabies nucleoprotein antigen by
      fluorescent antibody test (FAT). We describe the clinical evolution and
      sequential MRI brain changes in this child. CONCLUSIONS: Despite the uniformly
      dismal prognosis of human rabies, these unusual reports of survival of rabies
      patients may provide an impetus to explore newer therapeutic strategies for this
      otherwise fatal disease.

PMID- 26305827
TI  - Urinary detection of toscana virus nucleic acids in neuroinvasive infections.
AB  - BACKGROUND: Toscana virus (TOSV) is a sandfly-borne pathogen causing febrile
      diseases and neuroinvasive infections in humans. Definitive diagnosis of TOSV
      infections frequently requires the detection of viral RNA in cerebrospinal fluid
      (CSF) or in circulation, which can be achieved prior to seroconversion.
      OBJECTIVES: To evaluate TOSV excretion in urine and impact of urine as a
      diagnostic specimen. STUDY DESIGN: A total of 82 plasma, CSF and urine samples
      were collected from 24 individuals with a preliminary diagnosis of atypical viral
      encephalitis, where frequent bacterial fungal and viral causes were ruled out.
      Phlebovirus and WNV nucleic acids were investigated via real-time and nested
      polymerase chain reaction (PCR) assays. Commercial immunofluorescence assays were
      employed for viral IgM detection. Amplicons were characterized via cloning and
      sequencing. RESULTS: Phlebovirus PCR yielded positive results in 7 out of 14
      samples that comprise 4 plasma and 3 urine specimens from 3 individuals.
      Amplicons were characterized as TOSV genotype A. Investigation of the follow-up
      samples suggested that virus shedding in urine coincides or follows viremia.
      Despite conserved sequences observed in paired or sequential plasma-urine
      specimens, L693S substitution in the viral polymerase was characterized in a
      urine sample. CONCLUSIONS: These preliminary findings indicate that urine can be
      employed as a additional clinical sample for TOSV RNA detection in suspected
      cases, especially in individuals where specimens for viral diagnostics during the
      early stages of the infection are not available.

PMID- 26305828
TI  - Isolation of dengue serotype 3 virus from the cerebrospinal fluid of an
      encephalitis patient in Hai Phong, Vietnam in 2013.
AB  - Dengue encephalitis (DE) is characterized as unusual presentation of dengue
      infection. Despite the reports that DE accounts for only 1-5% of dengue cases,
      this disease tends to be increasingly reported to threaten global human health
      throughout dengue endemic areas particularly in Southeast Asia. The molecular
      information of clinically characterized, neurotropic dengue virus (DENV) in human
      beings is extremely scarce despite it playing an important role in deciphering
      the pathogenesis of dengue-related neurological cases. Here we report a case of
      DE caused by DENV3 genotype III in a male patient with atypical symptoms of DENV
      infection in Hai Phong, Vietnam in 2013. The virus isolated from the
      cerebrospinal fluid of this case-patient was closely related to DENV3 genotype
      III strains isolated from serum of two other patients, who manifested classical
      dengue in the same year and residing in the same area as the case-patient. It is
      noteworthy to mention that in 2013, DENV3 genotype III was detected for the first
      time in Vietnam. 

PMID- 26305829
TI  - Performance evaluation of the CHEMBIO DPP(r) (dual path platform) HIV-1/2 assay
      in early and established infections.
AB  - BACKGROUND: The availability of more accurate point-of-care technology could
      increase the number of persons aware of their HIV status. The DPP((r)) HIV-1/2
      assay is the first dual path platform rapid test (RT) approved in the U.S. that
      also received the Clinical Laboratory Improvement Amendments (CLIA) waiver for
      use with oral fluid and fingerstick and venous whole blood. OBJECTIVE: To
      evaluate the performance of the DPP((r)) HIV-1/2 assay with plasma specimens.
      STUDY DESIGN: Sensitivity and specificity of the assay were calculated from 696
      HIV-1 groups M (B and non-B subtypes) and O and HIV-2 (groups A and B) specimens
      and 505 HIV-negative specimens, respectively. Analysis of the assay performance
      in HIV-1 early infections was assessed by estimating the relative sensitivity of
      the RT before the Western blot (WB) becomes positive using a 50% cumulative
      frequency analysis and by comparing the reactivity with other Food and Drug
      Administration (FDA)-approved RTs. RESULTS: The sensitivity for established
      infection was 100% for HIV-1 and 100% for HIV-2. The specificity was 100%. The
      DPP((r)) HIV-1/2 assay performs similarly to most antibody-based RT approved by
      FDA in early HIV-1 infections. CONCLUSIONS: The DPP((r)) technology showed no
      significant improvement for detecting early infections over other lateral-flow
      RTs used in the U.S. Without more data on the DPP((r)) HIV-1/2 assay, especially
      from whole blood and oral fluid specimens collected during the early phase of
      infection, its performance as point-of-care technology remains to be assessed.

PMID- 26305830
TI  - Performance of a new rapid test for detecting anti-hepatitis E virus
      immunoglobulin M in immunocompetent and immunocompromised patients.
AB  - BACKGROUND: Hepatitis E virus (HEV) infections are widespread in both developing
      and developed countries. It is, therefore, important to assess the performance of
      systems for rapidly detecting anti-HEV immunoglobulin M antibodies in human sera.
      OBJECTIVES: To evaluate the diagnostic value of a new immunochromatographic
      assay, the HEV IgM rapid test (Wantai). STUDY DESIGN: Blood samples were taken
      from 30 acutely infected immunocompetent and 30 acutely infected
      immunocompromised patients, all with HEV RNA in their blood. Specificity and
      cross reactivity was assessed using samples from 30HEV RNA negative
      immunocompetent patients who had acute Epstein-Barr virus (EBV) or
      cytomegalovirus (CMV) infections and 30HEV RNA negative immunocompromised
      patients. The performance of the HEV IgM Rapid Test was compared to that of a
      conventional microplate enzyme immunoassay. RESULTS: The sensitivity of the rapid
      test in immunocompetent patients was 90% (95% CI: 72.1-100%), similar to that of
      the Wantai microplate assay (sensitivity: 96.6%, 95% CI: 78.77-100%; p=0.61). The
      sensitivity of the rapid test in immunocompromised patients was 73.3% (95% CI:
      55.4-91.2%) and that of the microplate assay was 83.3% (95% CI: 65.44-100%;
      p=0.53). The rapid test produced no false positive reactions with samples from
      HEV RNA negative patients; while the microplate assay gave two false positive
      results (3.3%). CONCLUSION: The new Wantai HEV IgM rapid test is easy to use and
      suitable for rapidly detecting acute hepatitis E infections in both
      immunocompetent and immunocompromised patients. However, HEV RNA must be detected
      using a molecular assay for diagnosing an HEV infection in anti-HEV IgM negative
      patients.

PMID- 26305831
TI  - Asymptomatic children might transmit human parechovirus type 3 to neonates and
      young infants.
AB  - BACKGROUND: Human parechovirus type 3 (HPeV3) epidemics occur worldwide and can
      lead to severe disease in neonates and young infants. Little is known about the
      source of HPeV3 infection. OBJECTIVES: To investigate the source of HPeV3
      infection and the role of asymptomatic children in the families of infected
      children. STUDY DESIGN: During a 2014 HPeV3 epidemic in Niigata, Japan, we
      analyzed (1) clinical information on sick contacts for 43 neonates and young
      infants with HPeV3-related disease diagnosed by PCR analysis of serum and/or
      cerebrospinal fluid and (2) stool samples from symptomatic and asymptomatic
      siblings/cousins of index patients. To confirm transmission, the P1 (VP0, VP3,
      and VP1) and 3D(pol) regions of HPeVs were sequenced and analyzed. RESULTS: Sick
      contact with family members was confirmed for 51% (n=22) of patients. Among the
      30 symptomatic family members, 67% (n=20) were siblings, 20% (n=6) were mothers,
      and 13% (n=4) were other relatives. Stool samples from symptomatic and
      asymptomatic siblings/cousins of 4 HPeV3-infected patients yielded positive
      results for HPeVs on PCR analysis. Furthermore, the P1 and 3D(pol) nucleotide
      sequences of family members were 100% identical to those of the respective index
      cases. CONCLUSIONS: Identification of genetically identical virus from HPeV3
      infected patients and asymptomatic children in their families suggests that the
      latter are a source of infection in neonates and young infants with HPeV3-related
      diseases.

PMID- 26305832
TI  - Approaches for monitoring of non virus-specific and virus-specific T-cell
      response in solid organ transplantation and their clinical applications.
AB  - Opportunistic viral infections are still a major complication following solid
      organ transplantation. Immune monitoring may allow the identification of patients
      at risk of infection and, eventually, the modulation of immunosuppressive
      strategies. Immune monitoring can be performed using virus-specific and non virus
      specific assays. This article describes and summarizes the pros and cons of the
      different technical approaches. Among the assays based on non virus-specific
      antigens, the enumeration of T-cell subsets, the quantification of cytokines and
      chemokines and the quantification of intracellular adenosine triphosphate
      following mitogen stimulation are described and their clinical applications to
      determine the risk for viral infection are discussed. In addition, current
      specific methods available for monitoring viral-specific T-cell responses are
      summarized, such as peptide-MHC multimer staining, intracellular cytokine
      staining, enzyme-linked immunospot and virus-specific IFN-gamma ELISA assays, and
      their clinical applications to determine the individual risk for opportunistic
      viral infections with human cytomegalovirus, Epstein-Barr virus and polyoma BK
      virus are discussed. The standardization of the procedure, the choice of the
      antigen(s) and the criteria to define cut-off values for positive responses are
      needed for some of these approaches before their implementation in the clinic.
      Nevertheless, immune monitoring combined with virological monitoring in
      transplant recipients is increasingly regarded as a helpful tool to identify
      patients at risk of infection as well as to assess treatment efficacy. 

PMID- 26305833
TI  - Discordant predictions of residual activity could impact dolutegravir
      prescription upon raltegravir failure.
AB  - BACKGROUND: Dolutegravir is approved for the treatment of HIV-1 patients exposed
      to other integrase inhibitors, but the decision to use dolutegravir in this
      setting should be informed by drug resistance testing. OBJECTIVES: This study
      determined the extent of disagreement in predicted residual dolutegravir activity
      after raltegravir use, and identified individual mutational patterns for which
      uncertainty exists among HIV-1 expert systems. STUDY DESIGN: Mutation patterns
      were classified in raltegravir signature pathways including positions 143, 148
      and 155, and interpreted into clinically informative resistance levels using
      genotypic drug resistance interpretation systems ANRS v24, HIVdb v7.0 and Rega
      v9.1.0, and instructions of dolutegravir use as approved by the Food and Drug
      Administration and the European Medicines Agency. RESULTS: In 216HIV-1 patients
      failing raltegravir-therapy, 87% patients displayed mutations associated with
      resistance towards integrase inhibitors. A total of 141 unique mutational
      patterns were observed, with N155H (25.4%), Q148H (16.2%) and Y143R (8.3%) the
      most prevalent signature mutations. The Q148 pathway occurred almost exclusively
      in HIV-1 subtype B viruses. Concordances in predicted dolutegravir susceptibility
      scores among 5 systems were obtained in 57.8% of patients, and concordant
      intermediate resistant and concordant resistant scores were only observed in 6.5%
      and 0.9% of patients, respectively. However, systems individually scored higher
      levels of dolutegravir intermediate resistance and resistance, ranging from 4.2%
      to 10.2% and from 14.8% to 22.7% of patients, respectively. A consensus on
      interpreting the extent of residual activity was lacking in 34.7% of patients and
      was highly resistance pathway-specific. CONCLUSIONS: Dolutegravir may potentially
      be effective in the majority of HIV-1 patients failing raltegravir, but concern
      over the uncertainty in predicted residual activity could withhold clinicians
      from prescribing dolutegravir during its clinical assessment.

PMID- 26305835
TI  - Bettering the lives of patients with end-stage renal disease with HomeChoice
      Claria with Sharesource: an interview with Dr. Bruce Culleton.
AB  - Interview with Dr. Bruce Culleton, Vice President, renal therapeutic area lead at
      Baxter by Tasnim Zahri (Commissioning Editor) I was fortunate enough to meet Dr.
      Bruce Culleton, Vice President, renal therapeutic area lead at Baxter (Deerfield,
      IL, USA), during the European Renal Association - European Dialysis and
      Transplant Association conference in London to discuss Baxter's newest dialysis
      system; the HomeChoice Claria automated peritoneal dialysis system with the
      Sharesource web-based connectivity platform. Recently awarded a CE mark,
      HomeChoice Claria with Sharesource is hoped to better the lives of patients with
      end-stage renal disease, enable effective connectivity between patients and
      clinicians and pave the way toward improved individualized care. 

PMID- 26305836
TI  - Evaluation of Zoll Medical's ResQCPR System for cardiopulmonary resuscitation.
AB  - Cardiac arrest remains a leading cause of death, currently affecting more than
      250,000 Americans annually. As recommended by the American Heart Association, the
      current standard of care for patients with an out-of-hospital cardiac arrest
      (OHCA) includes manual cardiopulmonary resuscitation (S-CPR). Survival with
      favorable neurological function for all patients following OHCA and treated with
      S-CPR averages <6%. The ResQCPR System is intended to provide greater circulation
      to the heart and brain compared with S-CPR, thereby increasing the likelihood of
      survival. A recent Phase III, multicenter randomized study demonstrated a 50%
      increase in survival to hospital discharge with favorable neurologic function in
      subjects with an OHCA of presumed cardiac etiology treated with the ResQCPR
      System compared with conventional CPR. The ResQCPR System has been recently
      approved by the FDA as a CPR adjunct to improve the likelihood of survival in
      adult patients with non-traumatic cardiac arrest. 

PMID- 26305837
TI  - Additive manufacturing in biomedical sciences and the need for definitions and
      norms.
AB  - The application of additive biomanufacturing represents one of the most rapidly
      advancing areas of biomedical science, in which engineers, scientists, and
      clinicians are contributing to the future of health care. The combined efforts of
      a large number of groups around the globe have developed a strong research thrust
      that has resulted in a large number of publications. Reviewing this body of
      literature, there is an increasing trend of research groups inventing their own
      definitions and terminology. This has made it difficult to find and compare the
      results. Therefore, to move the field constructively forward, it is a conditio
      sine qua non to clarify various terminologies and standards. Based on this
      background, this article advocates tightening the terminology and has the
      objective of penning out definitions that will ultimately allow the development
      of official industry standard terms, such as American Society for Testing and
      Materials and or International Organization for Standardization for technologies
      developed for Tissue Engineering and Regenerative Medicine. 

PMID- 26305838
TI  - Absorb bioresorbable stents for the treatment of coronary artery disease.
AB  - Bioresorbable stents are considered to be the 'fourth revolution' in percutaneous
      coronary intervention. The first clinically available Absorb((r)) bioresorbable
      device is made of poly-l-lactic acid polymer and elutes everolimus. The process
      of bioresorption is completed in 3 years. The introduction of this device into
      clinical practice went through several logical phases: first-in-man studies,
      randomized Absorb II study with moderately complex patients and lesions,
      registries of real life patient population and reports of challenging cases. The
      procedural results are excellent; many insights have been gained by intracoronary
      imaging. Intermediate-term outcomes are very encouraging both from imaging and
      from clinical perspectives. The issue of increased stent thrombosis rate was
      raised in one study, but other studies have been reassuring. Excellent lesion
      preparation, sizing and complete expansion of the Absorb device are crucial for
      optimal procedural and clinical results. Results of ongoing large randomized
      studies will determine the future role of this technology. 

PMID- 26305839
TI  - Device closure of periprosthetic paravalvular regurgitation.
AB  - Periprosthetic paravalvular regurgitation is an important sequel associated with
      prosthetic valves whether implanted surgically or via transcatheter approach.
      They can remain clinically silent or manifest as clinical heart failure,
      intravascular hemolysis or a combination of both. Periprosthetic defects are
      becoming increasingly recognized as a source of morbidity and mortality in
      patients with prosthetic heart valves and in the last few years, the management
      of this condition has evolved. This review aims to address the current knowledge
      on the pathophysiology, imaging modalities and management of these defects. It
      further details the principles, methodology and outcomes of catheter-based device
      therapy of periprosthetic paravalvular defects. 

PMID- 26305840
TI  - Development of inexpensive blood imaging systems: where are we now?
AB  - Clinical applications in the developing world, such as malaria and anemia
      diagnosis, demand a change in the medical paradigm of expensive care given in
      central locations by highly trained professionals. There has been a recent
      explosion in optical technologies entering the consumer market through the
      widespread adoption of smartphones and LEDs. This technology commoditization has
      enabled the development of small, portable optical imaging systems at an
      unprecedentedly low cost. Here, we review the state-of-the-field of the
      application of these systems for low-cost blood imaging with an emphasis on
      cellular imaging systems. In addition to some promising results addressing
      specific clinical issues, an overview of the technology landscape is provided. We
      also discuss several key issues that need to be addressed before these
      technologies can be commercialized. 

PMID- 26305841
TI  - Alternative approaches for assessing the socioeconomic benefits of medical
      devices: a systematic review.
AB  - Many medical devices offer improvements over current care that may be difficult
      to assess using standard methods of economic benefit measurement such as the
      quality-adjusted life-year (QALY). The objective of this research was to explore
      the extent to which these benefits have been measured and valued by alternative
      approaches, such as willingness-to-pay studies or discrete choice experiments. We
      undertook a systematic review of the literature from 1996 to 2013 to identify
      empirical studies on the benefits of medical devices using the alternative
      methodologies. The search resulted in 2772 hits, of which 2016 were considered
      not relevant to the study and 76 were duplicates. After further examination,
      there were 30 relevant empirical studies, of which 18 were willingness-to-pay and
      12 discrete choice experiments. This research demonstrates that while it is
      feasible to measure and value the attributes of devices using alternative
      approaches to standard quality-of-life measures, the literature is quite limited
      when compared with that for non-device technologies. 

PMID- 26305842
TI  - Highly Sensitive and Fast Response Colorimetric Humidity Sensors Based on
      Graphene Oxides Film.
AB  - Uniform graphene oxide (GO) film for optical humidity sensing was fabricated by
      dip-coating technique. The resulting GO thin film shows linear optical shifts in
      the visible range with increase of humidity in the whole relative humidity range
      (from dry state to 98%). Moreover, GO films exhibit ultrafast sensing to moisture
      within 250 ms because of the unique atomic thinness and superpermeability of GO
      sheets. The humidity sensing mechanism was investigated using XRD and computer
      simulation. The ultrasensitive humidity colorimetric properties of GOs film may
      enable many potential applications such as disposable humidity sensors for
      packaging, health, and environmental monitoring. 

PMID- 26305843
TI  - Formation of Langmuir Monolayers of Titanium Dioxide Nanoparticles at Air/Aqueous
      Interfaces by the Addition of Ions to the Subphase: Effect of Ion Concentration
      and Type.
AB  - A Langmuir monolayer of bare, hydrophilic TiO2 nanoparticles (diameter = 75 nm)
      was formed at an air/pH 5.8 aqueous interface by adding salt to the subphase. The
      effect of the concentration and type of salt in the subphase on the surface
      pressure-area per particle isotherms was determined. Increasing the concentration
      of NaCl from 0 to 3.8 M increased the maximum surface pressure (Pimax) and
      shifted the isotherms to a larger area per particle. The ion type also affected
      the area at which the close packing commenced and the value of Pimax. The
      presence of salt in the subphase also stabilized SiO2 nanoparticles, suggesting
      that the ions in the subphase interacted with the dioxide groups on the
      particles. The combination of structure making or borderline ions with structure
      breaking ions (LiCl, MgCl2, NaCl, and CaCl2) appeared to stabilize the
      particulate monolayers more than the combination of structure breaking ions (KBr
      and KCl). These results suggested that the particles were stabilized by a
      hydrogen bond network between the particles or the formation of a salt bridge
      between the particles. Attractions between particles at the air/aqueous interface
      caused the particles to aggregate, resulting in the particles becoming more
      stable at the air/aqueous interface. 

PMID- 26305844
TI  - Vibrational Spectroscopy Reveals Varying Structural Motifs in Cu(+)(CH4)(n) and
      Ag(+)(CH4)(n) (n = 1-6).
AB  - Vibrational spectra are measured for Cu(+)(CH4)(Ar)2, Cu(+)(CH4)2(Ar),
      Cu(+)(CH4)n (n = 3-6), and Ag(+)(CH4)n (n = 1-6) in the C-H stretching region
      (2500-3100 cm(-1)) using photofragment spectroscopy. Spectra are obtained by
      monitoring loss of Ar or CH4. Interaction with the metal ion produces substantial
      red shifts in the C-H stretches of proximate hydrogens. The magnitude of the
      shift reflects the metal-methane distance and the coordination to the metal ion
      of the methane hydrogens (eta(2) or eta(3)). The structures of the complexes are
      determined by comparing the measured spectra with spectra calculated for
      candidate geometries using the B3LYP and CAM-B3LYP density functionals with 6
      311++G(3df,3pd) and aug-cc-pVTZ-PP basis sets. Because of the d(10) electronic
      configuration of the metal ions, the complexes are expected to adopt symmetric
      structures, which is confirmed by the experiments. All of the complexes have
      eta(2) hydrogen coordination in the first shell, in accord with theoretical
      predictions; second-shell ligands sometimes show eta(3) hydrogen coordination.
      The vibrational spectrum of Cu(+)(CH4)(Ar)2 shows extensive structure due to
      Fermi resonance between the lowest-frequency C-H stretch and overtones of the H-C
      H bends. The Cu(+)(CH4) cluster has a smaller red shift in the lowest-frequency C
      H stretch than M(+)(CH4), M(+) = Co(+) (d(8)) and Ni(+) (d(9)). Although all
      three ions have similar binding energies, the metal-ligand electrostatic
      interaction is largest for Cu(+), while the contribution from covalent
      interactions is largest for Co(+). The larger ionic radius of Ag(+) leads to a
      larger metal-ligand distance and weaker interaction, resulting in substantially
      smaller red shifts than in the Cu(+) complexes. The Cu(+)(CH4)2 and Ag(+)(CH4)2
      clusters have symmetrical structures, with the methanes on opposite sides of the
      metal, while Cu(+)(CH4)3 and Ag(+)(CH4)3 adopt symmetrical, trigonal planar
      structures with all M-C distances equal. For Cu(+)(CH4)4, the tetrahedral
      structure dominates the observed spectrum, although a trigonal pyramidal
      structure may contribute; however, only the tetrahedral structure is observed for
      Ag(+)(CH4)4. The structures of Cu(+)(CH4)n and Ag(+)(CH4)n differ for clusters
      with n > 4. For copper complexes, these are primarily formed by adding outer
      shell methane ligand(s) to the tetrahedral n = 4 core. The observed spectra of
      the larger Ag(+) clusters are dominated by symmetrical structures in which all of
      the Ag-C distances are similar: Ag(+)(CH4)5 has a trigonal bipyramidal geometry
      and Ag(+)(CH4)6 is octahedral. 

PMID- 26305845
TI  - Doxycycline: new tricks for an old drug.

PMID- 26305846
TI  - Post-translesion synthesis repair.

PMID- 26305847
TI  - Tolerogenic citrullinated peptide for arthritis.

PMID- 26305848
TI  - Cracking the (tubulin) code of mitosis.

PMID- 26305849
TI  - Repair by a molecular DNA ambulance.

PMID- 26305850
TI  - Chromosome gains drive childhood ALL.

PMID- 26305851
TI  - The Ratio KL-6 to SLX in Serum for Prediction of the Occurrence of Drug-Induced
      Interstitial Lung Disease in Lung Cancer Patients with Idiopathic Interstitial
      Pneumonias Receiving Chemotherapy.
AB  - We retrospectively evaluated whether the ratio KL-6 to SLX in serum (K/S ratio)
      before chemotherapy was a predictor for the occurrence of drug-induced
      interstitial lung disease (D-ILD) in lung cancer patients with idiopathic
      interstitial pneumonias (IIPs). D-ILD occurred in 8 of 20 IIPs-positive cases and
      in 14 of 100 IIPs-negative cases (40 vs. 14%, p = .015). In IIPs-positive cases,
      the high K/S ratio (>20) before first-line chemotherapy had a tendency to
      increase the risk of D-ILD (p = .085). Serum K/S ratio may be a useful predictor
      for the occurrence of D-ILD in lung cancer patients with IIPs.

PMID- 26305852
TI  - Technology versus humanism: how patients perceive the use of electronic health
      records in physicians' offices--a qualitative study.
AB  - Electronic Health Records (EHRs) have the potential to improve the quality of
      care. In view of the accelerated adoption of EHRs, there is a need to understand
      conditions necessary for their effective use. Patients are the focus of
      healthcare and their perceptions and expectations need to be included in
      developing and implementing EHRs. The purpose of this study was to gather
      exploratory qualitative information from patients about their experiences and
      perceptions regarding the effects of EHRs on healthcare quality in physicians'
      offices. We conducted five focus groups with patients representing a random mix
      of diverse socio-demographic backgrounds in Oklahoma. Related to EHRs, patients
      reported improvements on the technical side of care but no change on the human
      side. They expressed concerns about the potential for breach of confidentiality
      and security of medical records. They were also concerned about the possibility
      of governmental agencies or insurance companies having unauthorized access to
      patient records. Patients differentiated between the human and technical sides of
      care and reported no change or improvement in the doctor-patient interaction.
      Patients have an important perspective on the use of EHRs and their perceptions
      and experiences should be considered in the development, adoption and
      implementation of EHRs. Otherwise, the use of EHRs may not be fully effective.
      There is also a need to educate patients about the potential benefits and risks
      of EHRs and the steps being taken to mitigate such risks. 

PMID- 26305853
TI  - Effect of Nanometric Lactobacillus plantarum in Kimchi on Dextran Sulfate Sodium
      Induced Colitis in Mice.
AB  - Nanometric Lactobacillus plantarum (nLp) is a processed form of Lab. plantarum
      derived from kimchi and is 0.5-1.0 MUm in size. This study was undertaken to
      determine the effect of nLp and kimchi plus nLp (K-nLp) on a dextran sulfate
      sodium (DSS)-induced mouse model of colitis. Animals fed nLp or K-nLp had longer
      colons, but lower colon weights per unit length than DSS controls. In addition,
      nLp- or K-nLp-fed animals showed lower levels of proinflammatory cytokines and
      inflammatory genes in serum and in colon tissues, lower populations of total
      bacteria, but higher populations of lactic acid bacteria in feces, and lower
      activities of fecal beta-glucosidase and beta-glucuronidase. Furthermore, these
      suppressive activities of nLp on colitis were equivalent to or higher than those
      of naive Lab. plantarum. Consequently, nLp was found to exhibit anticolitic
      effects, and the addition of nLp to kimchi was found to enhance the protective
      activity of kimchi against DSS-induced colitis. These results suggest that nLp
      might be an effective substitute for live probiotics and be useful as a
      functional ingredient with the anticolitic activity by the probiotic and food
      processing industries. 

PMID- 26305854
TI  - Development of a Real-Time PCR-Based Method for Analyzing Semen-Specific
      Unmethylated DNA Regions and Methylation Status in Aged Body Fluid Stains.
AB  - The detection of semen in forensic investigation is considered important evidence
      of sexual assault. In this study, we report the development of a real-time
      polymerase chain reaction-based method for identifying semen that can simply and
      rapidly analyze the semen-specific unmethylated region of the DACT1 gene. Using
      two fluorescent probes designed for the methylated or unmethylated status, this
      method could perform quantitative analysis of the methylation status in this
      region. Furthermore, this method was used to analyze various body fluid samples,
      including 29-year-old semen and blood stains. The results showed that this method
      can detect almost exclusively semen or nonsemen signals even in highly decomposed
      samples, while a few semen or nonsemen samples showed slight signals of the other
      fluorescence probe. Although there is still a need for further analysis such as
      setting thresholds to analyze unknown samples, this method could be a useful
      supplementary tool for identifying semen, especially in old stains such as those
      in cold-case investigations. 

PMID- 26305855
TI  - Herpes Zoster Immunization in Older Adults Has Big Benefits.
AB  - A case of acute herpes zoster neuralgia (shingles) in a 78-year-old patient is
      described. The value and importance of immunizing against herpes zoster to
      decrease the incidence and severity of both acute herpes zoster neuralgia and
      postherpetic neuralgia are described. --This report is adapted from paineurope
      2015: Issue 1, (c)Haymarket Medical Publications Ltd., and is presented with
      permission. paineurope is provided as a service to pain management by Mundipharma
      International, Ltd., and is distributed free of charge to health care
      professionals in Europe. Archival issues can be viewed via the Web site:
      www.paineurope.com , at which health professionals can find links to the original
      articles and request copies of the quarterly publication and access additional
      pain education and pain management resources.

PMID- 26305856
TI  - Acute predictors for mortality after severe TBI in Spain: Gender differences and
      clinical data.
AB  - OBJECTIVE: The main objective of this study is to determine whether gender
      affects global mortality and functional outcome after severe traumatic brain
      injury (TBI). METHODS: This retrospective cohort study included 629 patients with
      severe TBI (14.9% female) admitted to the ICU of a university hospital. Patients
      were split into gender groups to study potential differences in global mortality
      and functional outcome at ICU discharge and 6 months post-trauma using the GOS.
      The following variables were analysed: age, intracranial injury, injury
      mechanism, injury severity, factors contributing to secondary brain injury,
      monitoring level, treatment, complications, length of stay in the ICU and cause
      of death. RESULTS: No differences were found between gender groups in
      neuromonitoring level or surgical procedures. Women had higher APACHE II scores,
      a higher incidence of pre-hospital hypotension, anaemia and transfusion and
      higher mortality rates in the ICU (OR = 1.74; 95% CI = 1.09-2.77) and 6 months
      post-trauma (OR = 1.65; 95% CI = 1.02-2.67). There were no significant
      differences in functional outcome at ICU discharge or 6 months post-injury. The
      multivariate analysis did not show gender as an independent predictive factor in
      mortality after severe TBI. CONCLUSION: In this study, gender was not found to be
      an independent predictor for poorer outcome after severe TBI.

PMID- 26305857
TI  - The effect of fretting associated periodic cathodic potential shifts on the
      electrochemistry and in vitro biocompatibility of commercially pure titanium.
AB  - This study explored how periodic cathodic polarization of commercially pure
      titanium (cpTi) alters its electrochemical properties and biocompatibility. MC3T3
      E1 preosteoblast cells were cultured directly on cpTi samples and maintained at
      open circuit potential (OCP) for 24 h followed by an additional 24-h sequence of
      periodic cathodic polarization to -1000 or -750 mV (vs. Ag/AgCl) for 1 s followed
      by a 5-s recovery at OCP. Control experiments were performed where the samples
      were maintained at OCP throughout the entire test. Subsequent electrochemical
      impedance spectroscopy revealed both of the periodic cathodic polarization
      conditions significantly reduced the polarization resistance (Rp ), while only
      the -1000 mV condition significantly increased the capacitance (C) as compared to
      the controls. Scanning electron micrographs showed that the cells were fragmented
      and balled up on the samples periodically shifted to -1000 mV as compared to the
      cells that were well spread on the controls and samples periodically shifted to 
      750 mV. Additionally, live/dead fluorescence microscopy revealed that periodic
      polarizations to -1000 mV reduced cell viability to around 12% as compared to the
      greater than 95% cell viability observed on the controls and samples periodically
      polarized to -750 mV. This work showed that periodic cathodic potential shifts
      can notably alter the electrochemical behavior of cpTi and the viability and
      morphology of cells seeded directly onto its surface. (c) 2015 Wiley Periodicals,
      Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1591-1601, 2016.

PMID- 26305858
TI  - Structural Design Elements in Biological Materials: Application to
      Bioinspiration.
AB  - Eight structural elements in biological materials are identified as the most
      common amongst a variety of animal taxa. These are proposed as a new paradigm in
      the field of biological materials science as they can serve as a toolbox for
      rationalizing the complex mechanical behavior of structural biological materials
      and for systematizing the development of bioinspired designs for structural
      applications. They are employed to improve the mechanical properties, namely
      strength, wear resistance, stiffness, flexibility, fracture toughness, and energy
      absorption of different biological materials for a variety of functions (e.g.,
      body support, joint movement, impact protection, weight reduction). The
      structural elements identified are: fibrous, helical, gradient, layered, tubular,
      cellular, suture, and overlapping. For each of the structural design elements,
      critical design parameters are presented along with constitutive equations with a
      focus on mechanical properties. Additionally, example organisms from varying
      biological classes are presented for each case to display the wide variety of
      environments where each of these elements is present. Examples of current
      bioinspired materials are also introduced for each element. 

PMID- 26305859
TI  - Traffic-Related Air Pollution and Dementia Incidence in Northern Sweden: A
      Longitudinal Study.
AB  - BACKGROUND: Exposure to ambient air pollution is suspected to cause cognitive
      effects, but a prospective cohort is needed to study exposure to air pollution at
      the home address and the incidence of dementia. OBJECTIVES: We aimed to assess
      the association between long-term exposure to traffic-related air pollution and
      dementia incidence in a major city in northern Sweden. METHODS: Data on dementia
      incidence over a 15-year period were obtained from the longitudinal Betula study.
      Traffic air pollution exposure was assessed using a land-use regression model
      with a spatial resolution of 50 m * 50 m. Annual mean nitrogen oxide levels at
      the residential address of the participants at baseline (the start of follow-up)
      were used as markers for long-term exposure to air pollution. RESULTS: Out of
      1,806 participants at baseline, 191 were diagnosed with Alzheimer's disease
      during follow-up, and 111 were diagnosed with vascular dementia. Participants in
      the group with the highest exposure were more likely than those in the group with
      the lowest exposure to be diagnosed with dementia (Alzheimer's disease or
      vascular dementia), with a hazard ratio (HR) of 1.43 (95% CI: 0.998, 2.05 for the
      highest vs. the lowest quartile). The estimates were similar for Alzheimer's
      disease (HR 1.38) and vascular dementia (HR 1.47). The HR for dementia associated
      with the third quartile versus the lowest quartile was 1.48 (95% CI: 1.03, 2.11).
      A subanalysis that excluded a younger sample that had been retested after only 5
      years of follow-up suggested stronger associations with exposure than were
      present in the full cohort (HR = 1.71; 95% CI: 1.08, 2.73 for the highest vs. the
      lowest quartile). CONCLUSIONS: If the associations we observed are causal, then
      air pollution from traffic might be an important risk factor for vascular
      dementia and Alzheimer's disease.

PMID- 26305860
TI  - Toward an understanding of late life suicidal behavior: the role of lifespan
      developmental theory.
AB  - OBJECTIVES: Suicidal behavior in late life differs in important ways from
      suicidal behavior that occurs earlier in the lifespan, suggesting the possibility
      of developmental differences in the etiology of suicidal behavior. This paper
      examines late life suicidal behavior within the context of lifespan developmental
      theory. METHODS: This paper presents a conceptual framework for using lifespan
      developmental theory to better understand late life suicidal behavior. RESULTS:
      We argue that the motivational theory of lifespan development, which focuses on
      control, is particularly relevant to late life suicide. This theory posits that
      opportunities to exert control over important aspects of one's life diminish in
      late life as a result of declines in physical functioning and other factors, and
      that successful aging is associated with adaptive regulation of this
      developmental change. Although continued striving to meet goals is normative
      throughout the lifespan, most individuals also increase the use of compensatory
      strategies in old age or when faced with a decline in functioning. We propose
      that individuals who do not adapt to developmental changes by altering their
      strategies for exerting control will be at risk for suicidal behavior in late
      life. This paper reviews evidence that supports the importance of control with
      respect to suicidal outcomes in older adults, as well as findings regarding
      specific types of control strategies that may be related to suicide risk in older
      adults with health-related limitations. CONCLUSION: Although suicidal behavior is
      not a normal part of aging, the application of lifespan developmental theory may
      be useful in understanding and potentially preventing suicide among older adults.

PMID- 26305861
TI  - A new technique for generating disordered point-light animations for the study of
      biological motion perception.
AB  - Studies of biological motion perception often use stimuli depicting human actions
      portrayed via point-light (PL) displays. Typically, counterpart, or control,
      stimuli for PL biological motion are created by spatially scrambling motion
      trajectories of individual PL dots. Depending on the purpose of the study,
      however, this procedure may be inappropriate as a foil for genuine PL animations,
      because spatial scrambling not only disrupts coherent motion activity but also
      eliminates pair-wise motion relationships among dots and, unless corrected,
      alters the spatial spread of PL dot motions. We introduce a new technique for
      producing perturbed PL animations, called pair-wise shuffled motion, that
      preserves the elementary features of biological motion in spatial and motion
      energy domains and only disrupts the specific sense of global, coherent
      perception of biological motion. First we describe the procedure for creating
      pair-wise shuffled motion sequences. Next we compare unperturbed PL animations to
      pair-wise shuffled motion, to spatially scrambled motion, and to spatially
      constrained scrambled motion in terms of spatial distributions of the dots,
      spatiotemporal amplitude spectra derived from Fourier analysis of those
      sequences, and space-time motion energy associated with those perturbed
      animations. We then show that the results from those analyses generalize to a
      large family of PL animations, including the widely used PL walker. Finally we
      present results from a two-interval forced-choice biological-motion
      discrimination experiment comparing the robustness of scrambled and pair-wise
      shuffled motions as foil stimuli. Results from these comparisons suggest that
      pair-wise shuffled motion offers advantages as a foil stimulus compared to foils
      using the conventional scrambling technique. Pair-wise shuffled motion provides
      an additional, effective control display for evaluating PL biological motion
      perception in future psychophysical, computational, and imaging studies that
      focus on mechanisms of processing spatiotemporal information signifying
      biological motion within PL displays. 

PMID- 26305862
TI  - Testing the role of luminance edges in White's illusion with contour adaptation.
AB  - White's illusion is the perceptual effect that two equiluminant gray patches
      superimposed on a black-and-white square-wave grating appear different in
      lightness: A test patch placed on a dark stripe of the grating looks lighter than
      one placed on a light stripe. Although the effect does not depend on the aspect
      ratio of the test patches, and thus on the amount of border that is shared with
      either the dark or the light stripe, the context of each patch must, in a yet to
      be specified way, influence their lightness. We employed a contour adaptation
      paradigm (Anstis, 2013) to test the contribution of each of the test patches'
      edges to the perceived lightness of the test patches. We found that adapting to
      the edges that are oriented parallel to the grating slightly increased the
      lightness illusion, whereas adapting to the orthogonal edges abolished, or for
      some observers even reversed, the lightness illusion. We implemented a temporal
      adaptation mechanism in three spatial filtering models of lightness perception,
      and show that the models cannot account for the observed adaptation effects. We
      conclude that White's illusion is largely determined by edge contrast across the
      edge orthogonal to the grating, whereas the parallel edge has little or no
      influence. We suggest mechanisms that could explain this asymmetry. 

PMID- 26305863
TI  - A tetrachromatic display for the spatiotemporal control of rod and cone
      stimulation.
AB  - We present an apparatus that allows independent stimulation of rods and short (S)
      , middle (M)-, and long (L)-wavelength-sensitive cones. Previously presented
      devices allow rod and cone stimulation independently, but only for a spatially
      invariant stimulus design (Pokorny, Smithson, & Quinlan, 2004; Sun, Pokorny, &
      Smith, 2001b). We overcame this limitation by using two spectrally filtered
      projectors with overlapping projections. This approach allows independent rod and
      cone stimulation in a dynamic two-dimensional scene with appropriate resolution
      in the spatial, temporal, and receptor domains. Modulation depths were +/-15% for
      M-cones and L-cones, +/-20% for rods, and +/-50% for S-cones, all with respect to
      an equal-energy mesopic background at 3.4 cd/m2. Validation was provided by
      radiometric measures and behavioral data from two trichromats, one protanope, one
      deuteranope, and one night-blind observer. 

PMID- 26305865
TI  - Women's Health Identities in the Transition From Military Member to Service
      Veteran.
AB  - As servicewomen leave behind their military rank and status to become veterans,
      they must learn to effectively navigate a fragmented structure of care and
      communicate their health care needs. This study proposes a culture-centered
      approach to understanding how structural changes contribute to a reduction in
      positive health perception and behavior as active duty servicewomen transition to
      a veteran status. Results suggest during the process of disengagement from
      military cultural norms, women veterans' health care prevention service
      utilization decreases, and their physical and mental health decreases through the
      transition. These findings highlight the need for widely available and culturally
      appropriate programs to meet the needs of this unique patient population. 

PMID- 26305864
TI  - Wild-type APC predicts poor prognosis in microsatellite-stable proximal colon
      cancer.
AB  - BACKGROUND: APC mutations (APC-mt) occur in ~70% of colorectal cancers (CRCs),
      but their relationship to prognosis is unclear. METHODS: APC prognostic value was
      evaluated in 746 stage I-IV CRC patients, stratifying for tumour location and
      microsatellite instability (MSI). Microarrays were used to identify a gene
      signature that could classify APC mutation status, and classifier ability to
      predict prognosis was examined in an independent cohort. RESULTS: Wild-type APC
      microsatellite stable (APC-wt/MSS) tumours from the proximal colon showed poorer
      overall and recurrence-free survival (OS, RFS) than APC-mt/MSS proximal, APC
      wt/MSS distal and APC-mt/MSS distal tumours (OS HR?1.79, P?0.015; RFS HR?1.88,
      P?0.026). APC was a stronger prognostic indicator than BRAF, KRAS, PIK3CA, TP53,
      CpG island methylator phenotype or chromosomal instability status (P?0.036).
      Microarray analysis similarly revealed poorer survival in MSS proximal cancers
      with an APC-wt-like signature (P=0.019). APC status did not affect outcomes in
      MSI tumours. In a validation on 206 patients with proximal colon cancer, APC-wt
      like signature MSS cases showed poorer survival than APC-mt-like signature MSS or
      MSI cases (OS HR?2.50, P?0.010; RFS HR?2.14, P?0.025). Poor prognosis APC-wt/MSS
      proximal tumours exhibited features of the sessile serrated neoplasia pathway
      (P?0.016). CONCLUSIONS: APC-wt status is a marker of poor prognosis in MSS
      proximal colon cancer.

PMID- 26305866
TI  - Non-steroidal anti-inflammatory drug (NSAID) use is not associated with erectile
      dysfunction risk: results from the Prostate Cancer Prevention Trial.
AB  - OBJECTIVE: To evaluate the associations of non-steroidal anti-inflammatory drug
      (NSAID) use with risk of erectile dysfunction (ED), considering the indications
      for NSAID use. PATIENTS AND METHODS: We analysed data from 4 726 men in the
      placebo arm of the Prostate Cancer Prevention Trial (PCPT) without evidence of ED
      at baseline. Incident ED was defined as mild/moderate (decrease in normal
      function) or severe (absence of function). Proportional hazards models were used
      to estimate the covariate-adjusted associations of NSAID-related medical
      conditions and time-dependent NSAID use with ED risk. RESULTS: Arthritis (hazard
      ratio [HR] 1.56), chronic musculoskeletal pain (HR 1.35), general musculoskeletal
      complaints (HR 1.36), headaches (HR 1.44), sciatica (HR 1.50) and atherosclerotic
      disease (HR 1.60) were all significantly associated with an increased risk of
      mild/moderate ED, while only general musculoskeletal complaints (HR 1.22),
      headaches (HR 1.47) and atherosclerotic disease (HR 1.60) were associated with an
      increased risk of severe ED. Non-aspirin NSAID use was associated with an
      increased risk of mild/moderate ED (HR 1.16; P = 0.02) and aspirin use was
      associated with an increased risk of severe ED (HR 1.16; P = 0.03, respectively).
      The associations of NSAID use with ED risk were attenuated after controlling for
      indications for NSAID use. CONCLUSIONS: The modest associations of NSAID use with
      ED risk in the present cohort were probably attributable to confounding
      indications for NSAID use. NSAID use was not associated with ED risk.

PMID- 26305867
TI  - A rapid on-line method for mass spectrometric confirmation of a cysteine
      conjugated antibody-drug-conjugate structure using multidimensional
      chromatography.
AB  - Cysteine-conjugated antibody-drug conjugates (ADCs) are manufactured using
      controlled partial reduction and conjugation chemistry with drug payloads that
      typically occur in intervals of 0, 2, 4, 6, and 8. Control of heterogeneity is of
      particular importance to the quality of ADC product because drug loading and
      distribution can affect the safety and efficacy of the ADC. Liquid chromatography
      ultra-violet (LC-UV)-based methods can be used to acquire the drug distribution
      profiles of cysteine-conjugated ADCs when analyzed using hydrophobic interaction
      chromatography (HIC). However, alternative analysis techniques are often required
      for structural identification when conjugated drugs do not possess discrete ultra
      violet absorbance properties for precise assessment of the drug-to-antibody ratio
      (DAR). In this study, multidimensional chromatography was used as an efficient
      method for combining non-compatible techniques, such as HIC, with analysis by
      mass spectrometry (LC/LC/QTOF-MS) for rapid on-line structural elucidation of
      species observed in HIC distribution profiles of cysteine-conjugated ADCs. The
      methodology was tested using an IgG1 mAb modified by cysteine conjugation with a
      non-toxic drug mimic. Structural elucidation of peaks observed in the HIC
      analysis (1(st) dimension) were successfully identified based on their unique sub
      unit masses via mass spectrometry techniques once dissociation occurred under
      denaturing reversed phase conditions (2(nd) dimension). Upon identification, the
      DAR values were determined to be 2.83, 4.44, and 5.97 for 3 drug load levels (low
      , medium-, and high-loaded ADC batches), respectively, based on relative
      abundance from the LC-UV data. This work demonstrates that multidimensional
      chromatography coupled with MS, provides an efficient approach for on-line
      biotherapeutic characterization to ensure ADC product quality. 

PMID- 26305868
TI  - A new virtual ring-based system matrix generator for iterative image
      reconstruction in high resolution small volume PET systems.
AB  - A common approach to improving the spatial resolution of small animal PET
      scanners is to reduce the size of scintillation crystals and/or employ high
      resolution pixellated semiconductor detectors. The large number of detector
      elements results in the system matrix--an essential part of statistical iterative
      reconstruction algorithms--becoming impractically large. In this paper, we
      propose a methodology for system matrix modelling which utilises a virtual single
      layer detector ring to greatly reduce the size of the system matrix without
      sacrificing precision. Two methods for populating the system matrix are compared;
      the first utilises a geometrically-derived system matrix based on Siddon's ray
      tracer method with the addition of an accurate detector response function, while
      the second uses Monte Carlo simulation to populate the system matrix. The
      effectiveness of both variations of the proposed technique is demonstrated via
      simulations of PETiPIX, an ultra high spatial resolution small animal PET scanner
      featuring high-resolution DoI capabilities, which has previously been simulated
      and characterised using classical image reconstruction methods. Compression
      factors of 5 x 10(7) and 2.5 x 10(7)are achieved using this methodology for the
      system matrices produced using the geometric and Monte Carlo-based approaches,
      respectively, requiring a total of 0.5-1.2 GB of memory-resident storage. Images
      reconstructed from Monte Carlo simulations of various point source and phantom
      models, produced using system matrices generated via both geometric and
      simulation methods, are used to evaluate the quality of the resulting system
      matrix in terms of achievable spatial resolution and the CRC, CoV and CW-SSIM
      index image quality metrics. The Monte Carlo-based system matrix is shown to
      provide the best image quality at the cost of substantial one-off computational
      effort and a lower (but still practical) compression factor. Finally, a
      straightforward extension of the virtual ring method to a three dimensional
      virtual cylinder is demonstrated using a 3D DoI PET scanner.

PMID- 26305870
TI  - A Biodegradable Trilayered Barrier Membrane Composed of Sponge and Electrospun
      Layers: Hemostasis and Antiadhesion.
AB  - Placing a physical barrier between the injured site and the adjacent tissues is a
      very common and highly effective approach to prevent abdominal adhesions in these
      days. A biodegradable trilayered barrier was fabricated to prevent formation of
      abdominal adhesions, in which a poly(lactide-co-glycolide)/poly(lactide)-b
      poly(ethylene glycol) (PLGA/PLA-b-PEG) electrospun layer was sandwiched between
      layers of carboxymethyl chitosan (CMCS) sponge. The hydrophilic CMCS sponge
      layers with glycerin (GL) could adhere to the surface of wound easily, and
      present great hemostatic capability. The mechanism of the formation of adhesion
      related to blood clots acting with fibroblast cells was evaluated in detail. The
      blood clot acted as a "medium" inducing the fibroblast cells growth and
      proliferation, but had no special attraction on epithelial cells. CMCS sponge
      layer took away the blood clots during the swelling and dissolution stages. The
      electrospun layer promoted the growth of epithelial cells, but exhibited
      inhibition on the adhesion and spread of fibroblast cells, which ensured
      excellent effect of adhesion prevention. Evaluated by a rat model of sidewall
      defect-bowel abrasion, significant reductions of postoperative adhesion in its
      level and occurrence were observed in animals treated by the trilayered barrier. 

PMID- 26305871
TI  - A Simple Method for the Calculation of Lattice Energies of Inorganic Ionic
      Crystals Based on the Chemical Hardness.
AB  - This paper presents a new technique for estimation of lattice energies of
      inorganic ionic compounds using a simple formula. This new method demonstrates
      the relationship between chemical hardness and lattice energies of ionic
      compounds. Here chemical hardness values of ionic compounds are calculated via
      our molecular hardness equation. The results obtained using the present method
      and comparisons made by considering experimental data and the results from other
      theoretical methods in the literature showed that the new method allows easy
      evaluation of lattice energies of inorganic ionic crystals without the need for
      ab initio calculations and complex calculations. 

PMID- 26305869
TI  - Real-time fatigue reduction in emergency care clinicians: The SleepTrackTXT
      randomized trial.
AB  - BACKGROUND: We assessed performance characteristics and impact of a mobile phone
      text-message intervention for reducing intra-shift fatigue among emergency
      clinician shift workers. METHODS: We used a randomized controlled trial of 100
      participants. All participants received text-message assessments at the start,
      every 4 hr during, and at end of scheduled shifts over a 90-day period. Text
      message queries measured self-rated sleepiness, fatigue, and difficulty with
      concentration. Additional text-messages were sent to intervention participants to
      promote alertness. A performance measure of interest was compliance with
      answering text-messages. RESULTS: Ninety-nine participants documented 2,621
      shifts and responded to 36,073 of 40,947 text-messages (88% compliance rate).
      Intervention participants reported lower mean fatigue and sleepiness at 4 hr, 8
      hr, and at the end of 12 hr shifts compared to controls (P < 0.05). Intervention
      participants reported better sleep quality at 90-days compared to baseline (P =
      0.01). CONCLUSIONS: We showed feasibility and short-term efficacy of a text
      message based assessment and intervention tool.

PMID- 26305872
TI  - Hospital- and community-based interventions enhancing (re)employment for people
      with spinal cord injury: a systematic review.
AB  - STUDY DESIGN: Systematic Review. OBJECTIVES: To investigate the effect of
      interventions enhancing (re)employment following spinal cord injury (SCI).
      SETTING: Studies from multiple countries were included. METHODS: MEDLINE, EMBASE,
      Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, PsycINFO and
      SPORTDISCUS databases were searched. Randomized controlled trials (RCTs) and non
      randomized studies (NRSs) describing a hospital- or a community-based
      intervention aiming at employment in a SCI population were selected. Quality
      appraisal was done using the SIGN methodology, and the quality of evidence was
      graded using the Grade approach. Data extraction was performed according to the
      Cochrane Handbook. Employment rate and duration were primary outcomes. RESULTS:
      Only one RCT, including 201 patients describing an intervention over 1 and 2
      years, was of sufficient quality. In this study, the employment rate was 26%
      after 1 and 31% after 2 years for competitive work, compared with 10% in the
      treatment as usual-intervention site (TAU-IS) control group and 2% in the
      treatment as usual observational site (TAU-OS) after 1 and 2 years. Other studies
      were of low quality and describe higher employment rates from 36 to 100%.
      CONCLUSIONS: Only one RCT was of sufficient quality and showed evidence that a
      vocational rehabilitation programme based on the principles of supported
      employment integrated in a multidisciplinary team enhances employment for SCI
      people. As the vast majority of studies included in this review are of low
      methodological quality, further research is needed.

PMID- 26305873
TI  - Understanding decisions made about hepatitis C treatment by couples who inject
      drugs.
AB  - Efforts to increase the number of people having hepatitis C virus (HCV) treatment
      require understanding how to best deliver services to meet consumers' needs. The
      general health literature has examined the role that partners can play in
      supporting health outcomes. This study examines the experiences of couples who
      inject drugs in relation to knowledge of, decisions about and management of HCV
      treatment. This is a qualitative interview study of people who inject drugs in
      couples. Participants were recruited from harm reduction services in two major
      Australian cities. Couples were interviewed separately. Data were examined using
      the couple as the unit of analysis and to identify patterns of experience related
      to the HCV serostatus of couples. Knowledge of HCV and HCV treatment was low and
      variable but showed some relationship to serostatus. Decisions about HCV
      treatment were deeply informed by concerns regarding treatment side effects.
      Positive concordant couples considered 'staging' treatment to ensure that each
      partner could (in turn) care for the other. People with HCV in serodiscordant
      relationships may need specific support regarding HCV treatment information.
      Within positive concordant partnerships, our data indicated the need to support
      the HCV-positive 'carer' during their partner's treatment. Changing treatment
      regimens, and their anticipated lower side effect profiles, will need to be
      actively promoted to ensure that couples understand how these changes affect
      their treatment options. 

PMID- 26305874
TI  - Canagliflozin: a sodium glucose co-transporter 2 inhibitor for the treatment of
      type 2 diabetes mellitus.
AB  - The sodium glucose co-transporter 2 (SGLT2) inhibitor canagliflozin is a novel
      treatment option for adults with type 2 diabetes mellitus (T2DM). In patients
      with hyperglycemia, SGLT2 inhibition lowers plasma glucose levels by reducing the
      renal threshold for glucose (RTG ) and increasing urinary glucose excretion
      (UGE). Increased UGE is also associated with a mild osmotic diuresis and net
      caloric loss, which can lead to reductions in body weight and blood pressure
      (BP). After promising results from preclinical and phase I/II studies, the
      efficacy and safety of canagliflozin was evaluated in a comprehensive phase III
      development program in over 10,000 patients with T2DM on various background
      therapies. Canagliflozin improved glycemic control and provided reductions in
      body weight and BP versus placebo and active comparators in studies of up to 2
      years' duration. Canagliflozin was generally well tolerated, with higher
      incidences of adverse events (AEs) related to the mechanism of action, including
      genital mycotic infections and AEs related to osmotic diuresis. Results from the
      preclinical and clinical studies led canagliflozin to be the first-in-class SGLT2
      inhibitor approved in the United States, and support canagliflozin as a safe and
      effective therapeutic option across a broad range of patients with T2DM. 

PMID- 26305875
TI  - iTRAQ Quantitative Proteomic Comparison of Metastatic and Non-Metastatic Uveal
      Melanoma Tumors.
AB  - BACKGROUND: Uveal melanoma is the most common malignancy of the adult eye. The
      overall mortality rate is high because this aggressive cancer often metastasizes
      before ophthalmic diagnosis. Quantitative proteomic analysis of primary
      metastasizing and non-metastasizing tumors was pursued for insights into
      mechanisms and biomarkers of uveal melanoma metastasis. METHODS: Eight metastatic
      and 7 non-metastatic human primary uveal melanoma tumors were analyzed by LC
      MS/MS iTRAQ technology with Bruch's membrane/choroid complex from normal
      postmortem eyes as control tissue. Tryptic peptides from tumor and control
      proteins were labeled with iTRAQ tags, fractionated by cation exchange
      chromatography, and analyzed by LC MS/MS. Protein identification utilized the
      Mascot search engine and the human Uni-Prot/Swiss-Protein database with false
      discovery <= 1%; protein quantitation utilized the Mascot weighted average
      method. Proteins designated differentially expressed exhibited quantitative
      differences (p <= 0.05, t-test) in a training set of five metastatic and five non
      metastatic tumors. Logistic regression models developed from the training set
      were used to classify the metastatic status of five independent tumors. RESULTS:
      Of 1644 proteins identified and quantified in 5 metastatic and 5 non-metastatic
      tumors, 12 proteins were found uniquely in >= 3 metastatic tumors, 28 were found
      significantly elevated and 30 significantly decreased only in metastatic tumors,
      and 31 were designated differentially expressed between metastatic and non
      metastatic tumors. Logistic regression modeling of differentially expressed
      collagen alpha-3(VI) and heat shock protein beta-1 allowed correct prediction of
      metastasis status for each of five independent tumor specimens. CONCLUSIONS: The
      present data provide new clues to molecular differences in metastatic and non
      metastatic uveal melanoma tumors. While sample size is limited and validation
      required, the results support collagen alpha-3(VI) and heat shock protein beta-1
      as candidate biomarkers of uveal melanoma metastasis and establish a quantitative
      proteomic database for uveal melanoma primary tumors.

PMID- 26305876
TI  - Change in agitation in Alzheimer's disease in the placebo arm of a nine-week
      controlled trial.
AB  - BACKGROUND: Placebo responses raise significant challenges for the design of
      clinical trials. We report changes in agitation outcomes in the placebo arm of a
      recent trial of citalopram for agitation in Alzheimer's disease (CitAD). METHODS:
      In the CitAD study, all participants and caregivers received a psychosocial
      intervention and 92 were assigned to placebo for nine weeks. Outcomes included
      Neurobehavioral Rating Scale agitation subscale (NBRS-A), modified AD Cooperative
      Study-Clinical Global Impression of Change (CGIC), Cohen-Mansfield Agitation
      Inventory (CMAI), the Neuropsychiatric Inventory (NPI) Agitation/Aggression
      domain (NPI A/A) and Total (NPI-Total) and ADLs. Continuous outcomes were
      analyzed with mixed-effects modeling and dichotomous outcomes with logistic
      regression. RESULTS: Agitation outcomes improved over nine weeks: NBRS-A mean
      (SD) decreased from 7.8 (3.0) at baseline to 5.4 (3.2), CMAI from 28.7 (6.7) to
      26.7 (7.4), NPI A/A from 8.0 (2.4) to 4.9 (3.8), and NPI-Total from 37.3 (17.7)
      to 28.4 (22.1). The proportion of CGI-C agitation responders ranged from 21 to
      29% and was significantly different from zero. MMSE improved from 14.4 (6.9) to
      15.7 (7.2) and ADLs similarly improved. Most of the improvement was observed by
      three weeks and was sustained through nine weeks. The major predictor of
      improvement in each agitation measure was a higher baseline score in that
      measure. CONCLUSIONS: We observed significant placebo response which may be due
      to regression to the mean, response to a psychosocial intervention, natural
      course of symptoms, or nonspecific benefits of participation in a trial.

PMID- 26305877
TI  - Supporting Role for GTPase Rab27a in Hepatitis C Virus RNA Replication through a
      Novel miR-122-Mediated Effect.
AB  - The small GTPase Rab27a has been shown to control membrane trafficking and
      microvesicle transport pathways, in particular the secretion of exosomes. In the
      liver, high expression of Rab27a correlates with the development of
      hepatocellular carcinoma. We discovered that low abundance of Rab27a resulted in
      decreased hepatitis C virus (HCV) RNA and protein abundances in virus-infected
      cells. Curiously, both cell-associated and extracellular virus yield decreased in
      Rab27a depleted cells, suggesting that reduced exosome secretion did not cause
      the observed effect. Instead, Rab27a enhanced viral RNA replication by a
      mechanism that involves the liver-specific microRNA miR-122. Rab27a surrounded
      lipid droplets and was enriched in membrane fractions that harbor viral
      replication proteins, suggesting a supporting role for Rab27a in viral gene
      expression. Curiously, Rab27a depletion decreased the abundance of miR-122,
      whereas overexpression of miR-122 in Rab27a-depleted cells rescued HCV RNA
      abundance. Because intracellular HCV RNA abundance is enhanced by the binding of
      two miR-122 molecules to the extreme 5' end of the HCV RNA genome, the diminished
      amounts of miR-122 in Rab27a-depleted cells could have caused destabilization of
      HCV RNA. However, the abundance of HCV RNA carrying mutations on both miR-122
      binding sites and whose stability was supported by ectopically expressed miR-122
      mimetics with compensatory mutations also decreased in Rab27a-depleted cells.
      This result indicates that the effect of Rab27a depletion on HCV RNA abundance
      does not depend on the formation of 5' terminal HCV/miR-122 RNA complexes, but
      that miR-122 has a Rab27a-dependent function in the HCV lifecycle, likely the
      downregulation of a cellular inhibitor of HCV gene expression. These findings
      suggest that the absence of miR-122 results in a vulnerability not only to
      exoribonucleases that attack the viral genome, but also to upregulation of one
      more cellular factor that inhibit viral gene expression. 

PMID- 26305878
TI  - Determination of volatile organic compounds in the dried leaves of Salvia species
      by solid-phase microextraction coupled to gas chromatography mass spectrometry.
AB  - Salvia spp. are used throughout the world both for food and pharmaceutical
      purposes. In this study, a method involving headspace solid-phase microextraction
      combined with gas chromatography-mass spectrometry was developed, to establish
      the volatiles profile of dried leaves of four Iranian Salvia spp.: Salvia
      officinalis L., Salvia leriifolia Benth, Salvia macrosiphon Boiss. and two
      ecotypes of Salvia reuterana Boiss. A total of 95 volatiles were identified from
      the dried leaves of the five selected samples. Specifically, alpha-thujone was
      the main component of S. officinalis L. and S. macrosiphon Boiss. (34.40 and
      17.84%, respectively) dried leaves, S. leriifolia Benth was dominated by beta
      pinene (27.03%), whereas alpha-terpinene was the major constituent of the two
      ecotypes of S. reuterana Boiss. (21.67 and 13.84%, respectively). These results
      suggested that the proposed method can be considered as a reliable technique for
      isolating volatiles from aromatic plants, and for plant differentiation based on
      the volatile metabolomic profile. 

PMID- 26305879
TI  - The Role of Hemosiderin Excision in Seizure Outcome in Cerebral Cavernous
      Malformation Surgery: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND AND PURPOSE: Whether the excision of hemosiderin surrounding cerebral
      cavernous malformations (CCMs) is necessary to achieve a seizure-free result has
      been the subject of debate. Here, we report a systematic review of related
      literature up to Jan 1, 2015 including 594 patients to assess the effect of
      hemosiderin excision on seizure outcome in patients with CCMs by meta-analysis.
      METHODS: Ten studies comparing extended hemosiderin excision with only lesion
      resection were identified by searching the English-language literature. Meta
      analyses, subgroup analyses and sensitivity analysis were conducted to determine
      the association between hemosiderin excision and seizure outcome after surgery.
      RESULTS: Seizure outcome was significantly improved in the patients who underwent
      an extended excision of the surrounding hemosiderin (OR, 0.62; 95% CI: 0.42-0.91;
      P = 0.01). In subgroup analysis, studies from Asia (OR, 0.42; 95% CI: 0.25-0.71;
      P = 0.001), male-majority (female ratio < 50%) studies (OR, 0.56; 95% CI: 0.33
      0.96; P = 0.04), low occurrence rate of multiple CCMs (OR, 0.37; 95% CI: 0.20
      0.71; P = 0.003), cohort studies (OR, 0.44; 95% CI: 0.28-0.68; P = 0.78), longer
      duration of seizure symptoms (> 1 year) before surgery (OR, 0.43; 95% CI: 0.22
      0.84; P = 0.01), lesion diameter > 2 cm (OR, 0.41; 95% CI: 0.19-0.87; P = 0.02)
      and short-term (< 3 years) follow-up (OR, 0.48; 95% CI: 0.29-0.80; P = 0.005)
      tended to correlate with a significantly favorable outcome. CONCLUSION: Patients
      who underwent extended surrounding hemosiderin excision could exhibit
      significantly improved seizure outcomes compared to patients without hemosiderin
      excision. However, further well-designed prospective multiple-center RCT studies
      are still needed.

PMID- 26305880
TI  - Health-Related Physical Fitness in Healthy Untrained Men: Effects on VO2max, Jump
      Performance and Flexibility of Soccer and Moderate-Intensity Continuous Running.
AB  - The purpose of this study was to determine the effects of recreational soccer
      (SOC) compared to moderate-intensity continuous running (RUN) on all health
      related physical fitness components in healthy untrained men. Sixty-nine
      participants were recruited and randomly assigned to one of three groups, of
      which sixty-four completed the study: a soccer training group (SOC; n = 20, 34+/
      4 (means+/-SD) years, 78.1+/-8.3 kg, 179+/-4 cm); a running group (RUN; n = 21,
      32+/-4 years, 78.0+/-5.5 kg, 179+/-7 cm); or a passive control group (CON; n =
      23, 30+/-3 years, 76.6+/-12.0 kg, 178+/-8 cm). The training intervention lasted
      12 weeks and consisted of three 60-min sessions per week. All participants were
      tested for each of the following physical fitness components: maximal aerobic
      power, minute ventilation, maximal heart rate, squat jump (SJ), countermovement
      jump with arm swing (CMJ), sit-and-reach flexibility, and body composition. Over
      the 12 weeks, VO2max relative to body weight increased more (p<0.05) in SOC
      (24.2%, ES = 1.20) and RUN (21.5%, ES = 1.17) than in CON (-5.0%, ES = -0.24),
      partly due to large changes in body mass (-5.9, -5.7 and +2.6 kg, p<0.05 for SOC,
      RUN and CON, respectively). Over the 12 weeks, SJ and CMJ performance increased
      more (p<0.05) in SOC (14.8 and 12.1%, ES = 1.08 and 0.81) than in RUN (3.3 and
      3.0%, ES = 0.23 and 0.19) and CON (0.3 and 0.2%), while flexibility also
      increased more (p<0.05) in SOC (94%, ES = 0.97) than in RUN and CON (0-2%). In
      conclusion, untrained men displayed marked improvements in maximal aerobic power
      after 12 weeks of soccer training and moderate-intensity running, partly due to
      large decreases in body mass. Additionally soccer training induced pronounced
      positive effects on jump performance and flexibility, making soccer an effective
      broad-spectrum fitness training intervention. 

PMID- 26305881
TI  - Ecological Model to Predict Potential Habitats of Oncomelania hupensis, the
      Intermediate Host of Schistosoma japonicum in the Mountainous Regions, China.
AB  - BACKGROUND: Schistosomiasis japonica is a parasitic disease that remains endemic
      in seven provinces in the People's Republic of China (P.R. China). One of the
      most important measures in the process of schistosomiasis elimination in P.R.
      China is control of Oncomelania hupensis, the unique intermediate host snail of
      Schistosoma japonicum. Compared with plains/swamp and lake regions, the
      hilly/mountainous regions of schistosomiasis endemic areas are more complicated,
      which makes the snail survey difficult to conduct precisely and efficiently.
      There is a pressing call to identify the snail habitats of mountainous regions in
      an efficient and cost-effective manner. METHODS: Twelve out of 56 administrative
      villages distributed with O. hupensis in Eryuan, Yunnan Province, were randomly
      selected to set up the ecological model. Thirty out of the rest of 78 villages
      (villages selected for building model were excluded from the villages for
      validation) in Eryuan and 30 out of 89 villages in Midu, Yunnan Province were
      selected via a chessboard method for model validation, respectively. Nine-year
      average Normalized Difference Vegetation Index (NDVI) and Land Surface
      Temperature (LST) as well as Digital Elevation Model (DEM) covering Eryuan and
      Midu were extracted from MODIS and ASTER satellite images, respectively. Slope,
      elevation and the distance from every village to its nearest stream were derived
      from DEM. Suitable survival environment conditions for snails were defined by
      comparing historical snail presence data and remote sensing derived images.
      According to the suitable conditions for snails, environment factors, i.e. NDVI,
      LST, elevation, slope and the distance from every village to its nearest stream,
      were integrated into an ecological niche model to predict O. hupensis potential
      habitats in Eryuan and Midu. The evaluation of the model was assessed by
      comparing the model prediction and field investigation. Then, the consistency
      rate of model validation was calculated in Eryuan and Midu Counties,
      respectively. RESULTS: The final ecological niche model for potential O. hupensis
      habitats prediction comprised the following environmental factors, namely: NDVI
      (>= 0.446), LST (>= 22.70 degrees C), elevation (<= 2,300 m), slope (<= 11
      degrees ) and the distance to nearest stream (<= 1,000 m). The potential O.
      hupensis habitats in Eryuan distributed in the Lancang River basin and O.
      hupensis in Midu shows a trend of clustering in the north and spotty distribution
      in the south. The consistency rates of the ecological niche model in Eryuan and
      Midu were 76.67% and 83.33%, respectively. CONCLUSIONS: The ecological niche
      model integrated with NDVI, LST, elevation, slope and distance from every village
      to its nearest stream adequately predicted the snail habitats in the mountainous
      regions.

PMID- 26305882
TI  - Methyltransferase expression and tumor suppressor gene methylation in sporadic
      and familial colorectal cancer.
AB  - Molecular mechanisms underlying coordinated hypermethylation of multiple CpG
      islands in cancer remain unclear and studies of methyltransferase enzymes have
      arrived at conflicting results. We focused on DNMT1 and DNMT3B, DNA
      methyltransferases responsible for (de novo) methylation, and EZH2, histone
      (H3K27) methyltransferase, and examined their roles in tumor suppressor gene
      (TSG) methylation patterns we have previously established in sporadic and
      familial cancers. Our investigation comprised 165 tumors, stratified by tissue of
      origin (117 colorectal and 48 endometrial carcinomas) and sporadic vs. familial
      disease (57 sporadic vs. 60 familial, mainly Lynch syndrome, colorectal
      carcinomas). By immunohistochemical evaluation, EZH2 protein expression was
      associated with a TSG methylator phenotype. DNMT1, DNMT3B, and EZH2 were
      expressed at significantly higher levels in tumor vs. normal tissues. DNMT1 and
      EZH2 expression were positively correlated and higher in microsatellite-unstable
      vs. microsatellite-stable tumors, whether sporadic or hereditary. Ki-67
      expression mirrored the same pattern. Promoter methylation of the
      methyltransferase genes themselves was addressed as a possible cause behind their
      altered expression. While DNMT1 or EZH2 did not show differential methylation
      between normal and tumor tissues, DNMT3B analysis corroborated the regulatory
      role of a distal promoter region. Our study shows that methyltransferase
      expression in cancer depends on the tissue of origin, microsatellite-instability
      status, cellular proliferation, and--in the case of DNMT3B--promoter methylation
      of the respective gene. Translation of methyltransferase expression into DNA
      methylation appears complex as suggested by the fact that except for EZH2, no
      clear association between methyltransferase protein expression and TSG
      methylation was observed.

PMID- 26305883
TI  - Direct Chemical Vapor Deposition-Derived Graphene Glasses Targeting Wide Ranged
      Applications.
AB  - Direct growth of graphene on traditional glasses is of great importance for
      various daily life applications. We report herein the catalyst-free atmospheric
      pressure chemical vapor deposition approach to directly synthesizing large-area,
      uniform graphene films on solid glasses. The optical transparency and sheet
      resistance of such kinds of graphene glasses can be readily adjusted together
      with the experimentally tunable layer thickness of graphene. More significantly,
      these graphene glasses find a broad range of real applications by enabling the
      low-cost construction of heating devices, transparent electrodes, photocatalytic
      plates, and smart windows. With a practical scalability, the present work will
      stimulate various applications of transparent, electrically and thermally
      conductive graphene glasses in real-life scenarios. 

PMID- 26305884
TI  - CCNYL1, but Not CCNY, Cooperates with CDK16 to Regulate Spermatogenesis in Mouse.
AB  - Cyclin Y-like 1 (Ccnyl1) is a newly-identified member of the cyclin family and is
      highly similar in protein sequences to Cyclin Y (Ccny). However, the function of
      Ccnyl1 is poorly characterized in any organism. Here we found that Ccnyl1 was
      most abundantly expressed in the testis of mice and was about seven times higher
      than the level of Ccny. Male Ccnyl1-/- mice were infertile, whereas both male and
      female Ccny-/- mice displayed normal fertility. These results suggest that
      Ccnyl1, but not Ccny, is indispensable for male fertility. Spermatozoa obtained
      from Ccnyl1-/- mice displayed significantly impaired motility, and represented a
      thinned annulus region and/or a bent head. We found that the protein, but not the
      mRNA, level of cyclin-dependent kinase 16 (CDK16) was decreased in the testis of
      Ccnyl1-/- mice. Further study demonstrated that CCNYL1 interacted with CDK16 and
      this interaction mutually increased the stability of these two proteins.
      Moreover, the interaction increased the kinase activity of CDK16. In addition, we
      observed an alteration of phosphorylation levels of CDK16 in the presence of
      CCNYL1. We identified the phosphorylation sites of CDK16 by mass spectrometry and
      revealed that several phosphorylation modifications on the N-terminal region of
      CDK16 were indispensable for the CCNYL1 binding and the modulation of CDK16
      kinase activity. Our results therefore reveal a previously unrecognized role of
      CCNYL1 in regulating spermatogenesis through the interaction and modulation of
      CDK16. 

PMID- 26305885
TI  - Transport of Iodothyronines by Human L-Type Amino Acid Transporters.
AB  - Thyroid hormone (TH) transporters facilitate cellular TH influx and efflux, which
      is paramount for normal physiology. The L-type amino acid transporters LAT1 and
      LAT2 are known to facilitate TH transport. However, the role of LAT3, LAT4, and
      LAT5 is still unclear. Therefore, the aim of this study was to further
      characterize TH transport by LAT1 and LAT2 and to explore possible TH transport
      by LAT3, LAT4, and LAT5. FLAG-LAT1-5 constructs were transiently expressed in
      COS1 cells. LAT1 and LAT2 were cotransfected with the CD98 heavy chain. Cellular
      transport was measured using 10 nM (125)I-labeled T4, T3, rT3, 3,3'-T2, and 10
      MUM [(125)I]3'-iodotyrosine (MIT) as substrates. Intracellular metabolism of
      these substrates was determined in cells cotransfected with either of the LATs
      with type 1 or type 3 deiodinase. LAT1 facilitated cellular uptake of all
      substrates and LAT2 showed a net uptake of T3, 3,3'-T2, and MIT. Expression of
      LAT3 or LAT4 did not affect transport of T4 and T3 but resulted in the decreased
      cellular accumulation of 3,3'-T2 and MIT. LAT5 did not facilitate the transport
      of any substrate. Cotransfection with LAT3 or LAT4 strongly diminished the
      cellular accumulation of 3,3'-T2 and MIT by LAT1 and LAT2. These data were
      confirmed by metabolism studies. LAT1 and LAT2 show distinct preferences for the
      uptake of the different iodocompounds, whereas LAT3 and LAT4 specifically
      facilitate the 3,3'-T2 and MIT efflux. Together our findings suggest that
      different sets of transporters with specific influx or efflux capacities may
      cooperate to regulate the cellular thyroid state. 

PMID- 26305886
TI  - Mitotane Inhibits Sterol-O-Acyl Transferase 1 Triggering Lipid-Mediated
      Endoplasmic Reticulum Stress and Apoptosis in Adrenocortical Carcinoma Cells.
AB  - Adrenocortical carcinoma (ACC) is a rare malignancy that harbors a dismal
      prognosis in advanced stages. Mitotane is approved as an orphan drug for
      treatment of ACC and counteracts tumor growth and steroid hormone production.
      Despite serious adverse effects, mitotane has been clinically used for decades.
      Elucidation of its unknown molecular mechanism of action seems essential to
      develop better ACC therapies. Here, we set out to identify the molecular target
      of mitotane and altered downstream mechanisms by combining expression genomics
      and mass spectrometry technology in the NCI-H295 ACC model cell line. Pathway
      analyses of expression genomics data demonstrated activation of endoplasmic
      reticulum (ER) stress and profound alteration of lipid-related genes caused by
      mitotane treatment. ER stress marker CHOP was strongly induced and the two
      upstream ER stress signalling events XBP1-mRNA splicing and eukaryotic initiation
      factor 2 A (eIF2alpha) phosphorylation were activated by mitotane in NCI-H295
      cells but to a much lesser extent in four nonsteroidogenic cell lines. Lipid mass
      spectrometry revealed mitotane-induced increase of free cholesterol, oxysterols,
      and fatty acids specifically in NCI-H295 cells as cause of ER stress. We
      demonstrate that mitotane is an inhibitor of sterol-O-acyl-transferase 1 (SOAT1)
      leading to accumulation of these toxic lipids. In ACC tissue samples we show
      variable SOAT1 expression correlating with the response to mitotane treatment. In
      conclusion, mitotane confers adrenal-specific cytotoxicity and down-regulates
      steroidogenesis by inhibition of SOAT1 leading to lipid-induced ER stress.
      Targeting of cancer-specific lipid metabolism opens new avenues for treatment of
      ACC and potentially other types of cancer. 

PMID- 26305887
TI  - A Mixed Glucocorticoid/Mineralocorticoid Selective Modulator With Dominant
      Antagonism in the Male Rat Brain.
AB  - Adrenal glucocorticoid hormones are potent modulators of brain function in the
      context of acute and chronic stress. Both mineralocorticoid (MRs) and
      glucocorticoid receptors (GRs) can mediate these effects. We studied the brain
      effects of a novel ligand, C118335, with high affinity for GRs and modest
      affinity for MRs. In vitro profiling of receptor-coregulator interactions
      suggested that the compound is a "selective modulator" type compound for GRs that
      can have both agonistic and antagonistic effects. Its molecular profile for MRs
      was highly similar to those of the full antagonists spironolactone and
      eplerenone. C118335 showed predominantly antagonistic effects on hippocampal mRNA
      regulation of known glucocorticoid target genes. Likewise, systemic
      administration of C118335 blocked the GR-mediated posttraining corticosterone
      induced enhancement of memory consolidation in an inhibitory avoidance task.
      Posttraining administration of C118335, however, gave a strong and dose-dependent
      impairment of memory consolidation that, surprisingly, reflected involvement of
      MRs and not GRs. Finally, C118335 treatment acutely suppressed the hypothalamus
      pituitary-adrenal axis as measured by plasma corticosterone levels. Mixed GR/MR
      ligands, such as C118335, can be used to unravel the mechanisms of glucocorticoid
      signaling. The compound is also a prototype of mixed GR/MR ligands that might
      alleviate the harmful effects of chronic overexposure to endogenous
      glucocorticoids. 

PMID- 26305889
TI  - The NK3 Receptor Antagonist ESN364 Interrupts Pulsatile LH Secretion and
      Moderates Levels of Ovarian Hormones Throughout the Menstrual Cycle.
AB  - Women's health disorders such as uterine fibroids and endometriosis are currently
      treated by GnRH modulators that effectively suppress the hypothalamic-pituitary
      gonadal axis. The neurokinin-3 receptor (NK3R) is an alternative target with an
      important role in the modulation of this axis. In this report, we demonstrate
      that systemic administration of an NK3R antagonist (ESN364) prolongs the LH
      interpulse interval in ovarectomized ewes and significantly lowers plasma LH and
      FSH concentrations in castrated nonhuman primates (Macaca fascicularis).
      Moreover, daily oral dosing of ESN364 throughout the menstrual cycle in M
      fascicularis lowered plasma estradiol levels in a dose-dependent manner, although
      nadir levels of estradiol were maintained well above menopausal levels.
      Nevertheless, estradiol levels during the follicular phase were sufficiently
      inhibited at all doses to preclude the triggering of ovulation as evidenced by
      the absence of the LH surge and failure of a subsequent luteal phase rise in
      plasma progesterone concentrations, consistent with the absence of normal cycle
      changes in the uterus. Apart from the point at surge, FSH levels were not altered
      over the course of the menstrual cycle. These effects of ESN364 were reversible
      upon cessation of drug treatment. Together these data support the proposed role
      of neurokinin B-NK3R signaling in the control of pulsatile GnRH secretion.
      Furthermore, in contrast to GnRH antagonists, NK3R antagonists induce a partial
      suppression of estradiol and thereby offer a viable therapeutic approach to the
      treatment of ovarian sex hormone disorders with a mitigated risk of menopausal
      like adverse events in response to long-term drug exposure. 

PMID- 26305888
TI  - Cognitive and Disease-Modifying Effects of 11beta-Hydroxysteroid Dehydrogenase
      Type 1 Inhibition in Male Tg2576 Mice, a Model of Alzheimer's Disease.
AB  - Chronic exposure to elevated levels of glucocorticoids has been linked to age
      related cognitive decline and may play a role in Alzheimer's disease. In the
      brain, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) amplifies
      intracellular glucocorticoid levels. We show that short-term treatment of aged,
      cognitively impaired C57BL/6 mice with the potent and selective 11beta-HSD1
      inhibitor UE2316 improves memory, including after intracerebroventricular drug
      administration to the central nervous system alone. In the Tg2576 mouse model of
      Alzheimer's disease, UE2316 treatment of mice aged 14 months for 4 weeks also
      decreased the number of beta-amyloid (Abeta) plaques in the cerebral cortex,
      associated with a selective increase in local insulin-degrading enzyme (involved
      in Abeta breakdown and known to be glucocorticoid regulated). Chronic treatment
      of young Tg2576 mice with UE2316 for up to 13 months prevented cognitive decline
      but did not prevent Abeta plaque formation. We conclude that reducing
      glucocorticoid regeneration in the brain improves cognition independently of
      reduced Abeta plaque pathology and that 11beta-HSD1 inhibitors have potential as
      cognitive enhancers in age-associated memory impairment and Alzheimer's dementia.

PMID- 26305890
TI  - Evidence Suggesting a Role of Iron in a Mouse Model of Nephrogenic Systemic
      Fibrosis.
AB  - Nephrogenic systemic fibrosis is associated with gadolinium contrast exposure in
      patients with reduced kidney function and carries high morbidity and mortality.
      We have previously demonstrated that gadolinium contrast agents induce in vivo
      systemic iron mobilization and in vitro differentiation of peripheral blood
      mononuclear cells into ferroportin (iron exporter)-expressing fibrocytic cells.
      In the present study we examined the role of iron in a mouse model of nephrogenic
      systemic fibrosis. Chronic kidney disease was induced in 8-week-old male Balb/C
      mice with a two-step 5/6 nephrectomy surgery. Five groups of mice were studied:
      control (n = 5), sham surgery control (n = 5), chronic kidney disease control (n
      = 4), chronic kidney disease injected with 0.5 mmol/kg body weight of Omniscan 3
      days per week, for a total of 10 injections (n = 8), and chronic kidney disease
      with Omniscan plus deferiprone, 125 mg/kg, in drinking water (n = 9). Deferiprone
      was continued for 16 weeks until the end of the experiment. Mice with chronic
      kidney disease injected with Omniscan developed skin changes characteristic of
      nephrogenic systemic fibrosis including hair loss, reddening, ulceration, and
      skin tightening by 10 to 16 weeks. Histopathological sections demonstrated dermal
      fibrosis with increased skin thickness (0.25+/-0.06 mm, sham; 0.34+/-+0.3 mm,
      Omniscan-injected). Additionally, we observed an increase in tissue infiltration
      of ferroportin-expressing, fibrocyte-like cells accompanied by tissue iron
      accumulation in the skin of the Omniscan-treated mice. The deferiprone-treated
      group had significantly decreased skin thickness (p<0.05) and significantly
      decreased dermal fibrosis compared to the Omniscan-only group. In addition, iron
      chelation prevented tissue infiltration of ferroportin-expressing, fibrocyte-like
      cells. Our in vitro experiments demonstrated that exposure to Omniscan resulted
      in the release of catalytic iron and this was prevented by the iron chelator
      deferiprone. Deferiprone inhibited the differentiation of human peripheral blood
      mononuclear cells into ferroportin-expressing cells by immunohistochemical
      staining and western blot analysis. Our studies support an important role of iron
      in the pathophysiology of gadolinium chelate toxicity and nephrogenic systemic
      fibrosis. 

PMID- 26305892
TI  - Correction: Role of Key Salt Bridges in Thermostability of G. thermodenitrificans
      EstGtA2: Distinctive Patterns within the New Bacterial Lipolytic Enzyme Family
      XV.

PMID- 26305891
TI  - The Impact on Staff of Working with Personality Disordered Offenders: A
      Systematic Review.
AB  - BACKGROUND: Personality disordered offenders (PDOs) are generally considered
      difficult to manage and to have a negative impact on staff working with them.
      AIMS: This study aimed to provide an overview of studies examining the impact on
      staff of working with PDOs, identify impact areas associated with working with
      PDOs, identify gaps in existing research,and direct future research efforts.
      METHODS: The authors conducted a systematic review of the English-language
      literature from 1964-2014 across 20 databases in the medical and social sciences.
      RESULTS: 27 papers were included in the review. Studies identified negative
      impacts upon staff including: negative attitudes, burnout, stress, negative
      counter-transferential experiences; two studies found positive impacts of job
      excitement and satisfaction, and the evidence related to perceived risk of
      violence from PDOs was equivocal. Studies demonstrated considerable heterogeneity
      and meta-analysis was not possible. The overall level of identified evidence was
      low: 23 studies (85%) were descriptive only, and only one adequately powered
      cohort study was found. CONCLUSIONS: The review identified a significant amount
      of descriptive literature, but only one cohort study and no trials or previous
      systematic reviews of literatures. Clinicians and managers working with PDOs
      should be aware of the potential impacts identified, but there is an urgent need
      for further research focusing on the robust evaluation of interventions to
      minimise harm to staff working with offenders who suffer from personality
      disorder.

PMID- 26305893
TI  - Plastic Response of Tracheids in Pinus pinaster in a Water-Limited Environment:
      Adjusting Lumen Size instead of Wall Thickness.
AB  - The formation of wood results from cambial activity and its anatomical properties
      reflect the variability of environmental conditions during the growing season.
      Recently, it was found that wood density variations in conifers growing under
      cold-limited environment result from the adjustment of cell wall thickness (CWT)
      to temperature. Additionally, it is known that intra-annual density fluctuations
      (IADFs) are formed in response to precipitation after the summer drought.
      Although IADFs are frequent in Mediterranean conifers no study has yet been
      conducted to determine if these structures result from the adjustment of lumen
      diameter (LD) or CWT to soil water availability. Our main objective is to
      investigate the intra-ring variation of wood anatomical features (LD and CWT) in
      Pinus pinaster Ait. growing under a water-limited environment. We compared the
      tracheidograms of LD and CWT for the years 2010-2013 in P. pinaster growing in
      the west coast of Portugal. Our results suggest a close association between LD
      and soil moisture content along the growing season, reinforcing the role of water
      availability in determining tracheid size. Compared with CWT, LD showed a higher
      intra- and inter-annual variability suggesting its strong adjustment value to
      variations in water availability. The formation of a latewood IADF appears to be
      predisposed by higher rates of cell production in spring and triggered by early
      autumn precipitation. Our findings reinforce the crucial role of water
      availability on cambial activity and wood formation in Mediterranean conifers,
      and emphasize the high plasticity of wood anatomical features under Mediterranean
      climate. 

PMID- 26305895
TI  - Effects of Reducing Antimicrobial Use and Applying a Cleaning and Disinfection
      Program in Veal Calf Farming: Experiences from an Intervention Study to Control
      Livestock-Associated MRSA.
AB  - With the ultimate aim of containing the emergence of resistant bacteria, a Dutch
      policy was set in place in 2010 promoting a reduction of antimicrobial use (AMU)
      in food-producing animals. In this context, a study evaluated strategies to curb
      livestock-associated methicillin resistant Staphylococcus aureus (LA-MRSA). Fifty
      one veal calf farms were assigned to one of 3 study arms: RAB farms reducing
      antimicrobials by protocol; RAB-CD farms reducing antimicrobials by protocol and
      applying a cleaning and disinfection program; and Control farms without
      interventions. MRSA carriage was tested in week 0 and week 12 of 2 consecutive
      production cycles in farmers, family members and veal calves. Interventions were
      validated and a cyclic rise in MRSA-prevalence in animals was shown with a more
      moderate increase in RAB farms. Prevalence in humans declined parallel over time
      in the study arms but RAB farms were at the lowest MRSA levels from the beginning
      of the study. In RAB-CD farms, human and animal prevalence did not differ from
      Control farms and MRSA air loads were significantly higher than in the other
      study arms. Mimicking the national trend, an overall AMU decrease (daily dosages
      per animal per cycle (DDDA/C)) was observed over 4 pre-study and the 2 study
      cycles; this trend did not have a significant effect on a set of evaluated farm
      technical parameters. AMU was positively associated with MRSA across study arms
      (ORs per 10 DDDA/C increase = 1.26 for both humans (p = 0.07) and animals (p =
      0.12 in first cycle)). These results suggest that AMU reduction might be a good
      strategy for curbing MRSA in veal calf farming, however the specific cleaning and
      disinfecting program in RAB-CD farms was not effective. The drop in MRSA
      prevalence in people during the study could be attributed to the observed long
      term AMU decreasing trend. 

PMID- 26305896
TI  - Effects of Aging on Arm Swing during Gait: The Role of Gait Speed and Dual
      Tasking.
AB  - Healthy walking is characterized by pronounced arm swing and axial rotation.
      Aging effects on gait speed, stride length and stride time variability have been
      previously reported, however, less is known about aging effects on arm swing and
      axial rotation and their relationship to age-associated gait changes during usual
      walking and during more challenging conditions like dual tasking. Sixty healthy
      adults between the ages of 30-77 were included in this study designed to address
      this gap. Lightweight body fixed sensors were placed on each wrist and lower
      back. Participants walked under 3 walking conditions each of 1 minute: 1)
      comfortable speed, 2) walking while serially subtracting 3's (Dual Task), 3)
      walking at fast speed. Aging effects on arm swing amplitude, range, symmetry,
      jerk and axial rotation amplitude and jerk were compared between decades of age
      (30-40; 41-50; 51-60; 61-77 years). As expected, older adults walked slower (p =
      0.03) and with increased stride variability (p = 0.02). Arm swing amplitude
      decreased with age under all conditions (p = 0.04). In the oldest group, arm
      swing decreased during dual task and increased during the fast walking condition
      (p<0.0001). Similarly, arm swing asymmetry increased during the dual task in the
      older groups (p<0.004), but not in the younger groups (p = 0.67). Significant
      differences between groups and within conditions were observed in arm swing jerk
      (p<0.02), axial rotation amplitude (p<0.02) and axial jerk (p<0.001). Gait speed,
      arm swing amplitude of the dominant arm, arm swing asymmetry and axial rotation
      jerk were all independent predictors of age in a multivariate model. These
      findings suggest that the effects of gait speed and dual tasking on arm swing and
      axial rotation during walking are altered among healthy older adults. Follow-up
      work is needed to examine if these effects contribute to reduced stability in
      aging. 

PMID- 26305898
TI  - The Augmenting Effects of Desolvation and Conformational Energy Terms on the
      Predictions of Docking Programs against mPGES-1.
AB  - In this study we introduce a rescoring method to improve the accuracy of docking
      programs against mPGES-1. The rescoring method developed is a result of extensive
      computational study in which different scoring functions and molecular
      descriptors were combined to develop consensus and rescoring methods. 127 mPGES-1
      inhibitors were collected from literature and were segregated into training and
      external test sets. Docking of the 27 training set compounds was carried out
      using default settings in AutoDock Vina, AutoDock, DOCK6 and GOLD programs. The
      programs showed low to moderate correlation with the experimental activities. In
      order to introduce the contributions of desolvation penalty and conformation
      energy of the inhibitors various molecular descriptors were calculated. Later,
      rescoring method was developed as empirical sum of normalised values of docking
      scores, LogP and Nrotb. The results clearly indicated that LogP and Nrotb
      recuperate the predictions of these docking programs. Further the efficiency of
      the rescoring method was validated using 100 test set compounds. The accurate
      prediction of binding affinities for analogues of the same compounds is a major
      challenge for many of the existing docking programs; in the present study the
      high correlation obtained for experimental and predicted pIC50 values for the
      test set compounds validates the efficiency of the scoring method. 

PMID- 26305899
TI  - A Reaction-Based Fluorescent Probe for Imaging of Formaldehyde in Living Cells.
AB  - Formaldehyde (FA), in the 0.2-0.4 mM range, is produced and maintained
      endogenously via enzymatic pathways. At these levels, FA can promote cell
      proliferation as well as mediate memory formation. Once elevated, FA stress is
      known to induce cognitive impairments, memory loss, and neurodegeneration owing
      to its potent DNA and protein cross-linking mechanisms. Optical imaging is a
      powerful noninvasive approach used to study FA in living systems; however,
      biocompatible chemical probes for FA are currently lacking. Herein, we report the
      design, synthesis, and biological evaluation of Formaldehyde Probe 1 (FP1), a new
      fluorescent indicator based on the 2-aza-Cope sigmatropic rearrangement. The
      remarkable sensitivity, selectivity, and photostability of FP1 has enabled us to
      visualize FA in live HEK293TN and Neuroscreen-1 cells. We envision that FP1 will
      find widespread applications in the study of FA associated with normal and
      pathological processes. 

PMID- 26305900
TI  - (-)-Tarchonanthuslactone: Design of New Analogues, Evaluation of their
      Antiproliferative Activity on Cancer Cell Lines, and Preliminary Mechanistic
      Studies.
AB  - Natural products containing the alpha,beta-unsaturated delta-lactone skeleton
      have been shown to possess a variety of biological activities. The natural
      product (-)-tarchonanthuslactone (1) possessing this privileged scaffold is a
      popular synthetic target, but its biological activity remains underexplored.
      Herein, the total syntheses of dihydropyran-2-ones modeled on the structure of 1
      were undertaken. These compounds were obtained in overall yields of 17-21 % based
      on the Keck asymmetric allylation reaction and were evaluated in vitro against
      eight different cultured human tumor cell lines. We further conducted initial
      investigation into the mechanism of action of selected analogues. Dihydropyran-2
      one 8 [(S,E)-(6-oxo-3,6-dihydro-2H-pyran-2-yl)methyl 3-(3,4
      dihydroxyphenyl)acrylate], a simplified analogue of (-)-tarchonanthuslactone (1)
      bearing an additional electrophilic site and a catechol system, was the most
      cytotoxic and selective compound against six of the eight cancer cell lines
      analyzed, including the pancreatic cancer cell line. Preliminary studies on the
      mechanism of action of compound 8 on pancreatic cancer demonstrated that
      apoptotic cell death takes place mediated by an increase in the level of reactive
      oxygen species. It appears as though compound 8, possessing two Michael acceptors
      and a catechol system, may be a promising scaffold for the selective killing of
      cancer cells, and thus, it deserves further investigation to determine its
      potential for cancer therapy. 

PMID- 26305901
TI  - Wood species affect the degradation of crude oil in beach sand.
AB  - The addition of wood chips as a co-substrate can promote the degradation of oil
      in soil. Therefore, in the present study, the tree species-specific impact of
      wood chips of Scots pine (Pinus sylvestris L.), Norway spruce (Picea abies L.)
      and Western balsam poplar (Populus trichocarpa L.) on the degradation of crude
      oil was tested in beach sand in a 4-week incubation experiment. The CO2-C release
      increased in the order of control without wood chips < +spruce < +pine < +poplar.
      Initial and final hydrocarbon concentrations (C10 to C40), as indicators for the
      oil degradation, were determined with gas chromatography-flame ionization
      detection (GC-FID). The degradation increased for the light fraction (C10 to
      C22), the heavy fraction (C23 to C40) as well as the whole range (C10 to C40) in
      the order of control without wood chips (f(degrad.) = 23% vs. 0% vs. 12%) <
      +poplar (f(degrad.) = 49% vs. 19% vs. 36%) < +spruce (f(degrad.) = 55% vs. 34%
      vs. 46%) < +pine (f(degrad.) = 60% vs. 44% vs. 53%), whereas the heavy fraction
      was less degraded in comparison to the light fraction. It can be concluded, that
      the tree species-specific wood quality is a significant control of the impact on
      the degradation of hydrocarbons, and pine wood chips might be promising, possibly
      caused by their lower decomposability and lower substrate replacement than the
      other wood species.

PMID- 26305902
TI  - [Great need for emergency physicians on call time].

PMID- 26305897
TI  - Genome-Wide Association and Trans-ethnic Meta-Analysis for Advanced Diabetic
      Kidney Disease: Family Investigation of Nephropathy and Diabetes (FIND).
AB  - Diabetic kidney disease (DKD) is the most common etiology of chronic kidney
      disease (CKD) in the industrialized world and accounts for much of the excess
      mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients
      with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic
      control, DKD aggregates in families and has higher incidence rates in African,
      Mexican, and American Indian ancestral groups relative to European populations.
      The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome
      wide association study (GWAS) contrasting 6,197 unrelated individuals with
      advanced DKD with healthy and diabetic individuals lacking nephropathy of
      European American, African American, Mexican American, or American Indian
      ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539
      additional European American, African American and American Indian DKD cases and
      non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and
      replication set results identified genome-wide significant evidence for
      association between DKD and rs12523822 on chromosome 6q25.2 in American Indians
      (P = 5.74x10-9). The strongest signal of association in the trans-ethnic meta
      analysis was with a SNP in strong linkage disequilibrium with rs12523822
      (rs955333; P = 1.31x10-8), with directionally consistent results across ethnic
      groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a
      region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a
      gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive
      evidence of association with DKD, within and across populations. These data
      identify a novel DKD susceptibility locus with consistent directions of effect
      across diverse ancestral groups and provide insight into the genetic architecture
      of DKD. 

PMID- 26305903
TI  - [Decision on "future power of attorney" cannot be delayed].

PMID- 26305904
TI  - [Reply to Ylva Vladic Stjernholm: the medical association hopes for a continued
      debate on professional ethics].

PMID- 26305905
TI  - Mutations in the DI-DII Linker of Human Parainfluenza Virus Type 3 Fusion Protein
      Result in Diminished Fusion Activity.
AB  - Human parainfluenza virus type 3 (HPIV3) can cause severe respiratory tract
      diseases in infants and young children, but no licensed vaccines or antiviral
      agents are currently available for treatment. Fusing the viral and target cell
      membranes is a prerequisite for its entry into host cells and is directly
      mediated by the fusion (F) protein. Although several domains of F are known to
      have important effects on regulating the membrane fusion activity, the roles of
      the DI-DII linker (residues 369-374) of the HPIV3 F protein in the fusogenicity
      still remains ill-defined. To facilitate our understanding of the role of this
      domain might play in F-induced cell-cell fusion, nine single mutations were
      engineered into this domain by site-directed mutagenesis. A vaccinia virus-T7 RNA
      polymerase transient expression system was employed to express the wild-type or
      mutated F proteins. These mutants were analyzed for membrane fusion activity,
      cell surface expression, and interaction between F and HN protein. Each of the
      mutated F proteins in this domain has a cell surface expression level similar to
      that of wild-type F. All of them resulted in a significant reduction in fusogenic
      activity in all steps of membrane fusion. Furthermore, all these fusion-deficient
      mutants reduced the amount of the HN-F complexes at the cell surface. Together,
      the results of our work suggest that this region has an important effect on the
      fusogenic activity of F. 

PMID- 26305907
TI  - CaF2-Based Near-Infrared Photocatalyst Using the Multifunctional CaTiO3
      Precursors as the Calcium Source.
AB  - Multistage formation of fluoride upconversion agents from the related
      semiconductor precursors provides a promising route for the fabrication of near
      infrared (NIR) photocatalysts with high photocatalytic activities. Herein, the
      cotton templated CaTiO3 "semiconduction" precursors (C-CaTiO3) were used to
      synthesize the NIR photocatalyst of Er3+/Tm3+/Yb3+-(CaTiO3/CaF2/TiO2) (C-ETYCCT),
      and the functions of the Ca2+ source for CaF2 and the heterostructure formations
      were displayed by C-CaTiO3. The generated CaF2 acted as the host material for the
      lanthanide ions, and the heterostructures were constructed among anatase, rutile,
      and the remaining CaTiO3. The induced oxygen vacancies and Ti3+ ions enabled the
      samples to utilize most of the upconversion luminescence for photocatalysis. The
      NIR driven degradation rate of methyl orange (MO) over C-ETYCCT reached 52.34%,
      which was 1.6 and 2.5 times higher than those of Er3+/Tm3+/Yb3+-(CaTiO3/TiO2) (C
      ETYCT) and Er3+/Tm3+/Yb3+-(CaTiO3/CaF2) (C-ETYCC), respectively. The degradation
      rates of MO and salicylic acid over C-ETYCCT with UV-vis-NIR light irradiation
      were also much higher than those of other samples, which were mainly results of
      the contributions of its high upconversion luminescence and the efficient
      electron-hole pair separation.

PMID- 26305906
TI  - Curcumin Improves the Tumoricidal Effect of Mitomycin C by Suppressing ABCG2
      Expression in Stem Cell-Like Breast Cancer Cells.
AB  - Cancer cells with stem cell-like properties contribute to the development of
      resistance to chemotherapy and eventually to tumor relapses. The current study
      investigated the potential of curcumin to reduce breast cancer stem cell (BCSC)
      population for sensitizing breast cancer cells to mitomycin C (MMC) both in vitro
      and in vivo. Curcumin improved the sensitivity of paclitaxel, cisplatin, and
      doxorubicin in breast cancer cell lines MCF-7 and MDA-MB-231, as shown by the
      more than 2-fold decrease in the half-maximal inhibitory concentration of these
      chemotherapeutic agents. In addition, curcumin sensitized the BCSCs of MCF-7 and
      MDA-MB-231 to MMC by 5- and 15-fold, respectively. The BCSCs could not grow to
      the fifth generation in the presence of curcumin and MMC. MMC or curcumin alone
      only marginally reduced the BCSC population in the mammospheres; however,
      together, they reduced the BCSC population in CD44+CD24-/low cells by more than
      75% (29.34% to 6.86%). Curcumin sensitized BCSCs through a reduction in the
      expression of ATP-binding cassette (ABC) transporters ABCG2 and ABCC1. We
      demonstrated that fumitremorgin C, a selective ABCG2 inhibitor, reduced BCSC
      survival to a similar degree as curcumin did. Curcumin sensitized breast cancer
      cells to chemotherapeutic drugs by reducing the BCSC population mainly through a
      reduction in the expression of ABCG2. 

PMID- 26305908
TI  - Fluoroquinolones versus beta-Lactam/beta-Lactamase Inhibitors in Outpatients with
      Chronic Obstructive Pulmonary Disease and Pneumonia: A Nationwide Population
      Based Study.
AB  - BACKGROUND: Studies on the association between antibiotic treatment and outcomes
      in outpatients with chronic obstructive pulmonary disease (COPD) and pneumonia
      are scarce. This study aimed to evaluate the effectiveness of fluoroquinolones
      and beta-lactam/beta-lactamase inhibitors for pneumonia in COPD outpatients.
      METHODS: We conducted a retrospective cohort study and identified 4,851 episodes
      of pneumonia among COPD outpatients treated with fluoroquinolones or beta
      lactam/beta-lactamase inhibitors from the Taiwan National Health Insurance
      Research Database during 2002-2011. Using the propensity score analysis, 1,296
      pairs of episodes were matched for the demographic and clinical characteristics.
      The primary outcome was pneumonia/empyema-related hospitalization or emergency
      department (ED) visits, and the secondary outcomes were treatment failure, all
      cause mortality and medical costs within 30 days. RESULTS: Compared with episodes
      treated with beta-lactam/beta-lactamase inhibitors, episodes treated with
      fluoroquinolones had similar clinical outcomes. The rates of pneumonia/empyema
      related hospitalization or ED visits were 3.9% and 3.5% in the fluoroquinolone
      and beta-lactam/beta-lactamase inhibitor groups, respectively (adjusted hazard
      ratio [aHR], 1.11; 95% confidence interval [CI], 0.74-1.66). The percentage of
      treatment failure and all-cause mortality were 28.2% versus 31.3% (adjusted odds
      ratio, 0.86; 95% CI, 0.73-1.02) and 0.5% versus 0.4% (aHR, 1.40; 95% CI, 0.45
      4.41) in the fluoroquinolone and beta-lactam/beta-lactamase inhibitor groups,
      respectively. The medical expenditures, including total medical costs (528 versus
      455 US dollars) and pneumonia-related costs (202 vs. 155 USD) were also balanced
      between the two treatment groups (both P >0.05). CONCLUSIONS: For pneumonia in
      COPD outpatients, fluoroquinolones were associated with similar clinical outcomes
      and medical expenditures compared with beta-lactam/beta-lactamase inhibitors.

PMID- 26305909
TI  - Modulation of Phenol Oxidation in Cofacial Dyads.
AB  - The presentation of two phenols on a xanthene backbone is akin to the tyrosine
      dyad (Y730 and Y731) of ribonucleotide reductase. X-ray crystallography reveals
      that the two phenol moieties are cofacially disposed at 4.35 A. Cyclic
      voltammetry reveals that phenol oxidation is modulated within the dyad, which
      exhibits a splitting of one-electron waves with the second oxidation of the
      phenol dyad occurring at larger positive potential than that of a typical phenol.
      In contrast, a single phenol appended to a xanthene exhibits a two-electron
      process, consistent with reported oxidation pathways of phenols in acetonitrile.
      The perturbation of the phenol potential by stacking is reminiscent of a similar
      effect for guanines stacked within DNA base pairs. 

PMID- 26305910
TI  - Multi-frequency (S, X, Q and W-band) EPR and ENDOR Study of Vanadium(IV)
      Incorporation in the Aluminium Metal-Organic Framework MIL-53.
AB  - Doping the well-known metal-organic framework MIL-53(Al) with vanadium(IV) ions
      leads to significant changes in the breathing behaviour and might have
      repercussions on the catalytic behaviour as well. To understand the properties of
      such a doped framework, it is necessary to determine where dopant ions are
      actually incorporated. Electron paramagnetic resonance (EPR) and electron-nuclear
      double resonance (ENDOR) are applied to reveal the nearest environment of the
      paramagnetic vanadium(IV) dopant ions. EPR spectra of as-synthesised vanadium
      doped MIL-53 are recorded at S-, X-, Q- and W-band microwave frequencies. The EPR
      spectra suggest that at low dopant concentrations (1.0-2.6 mol %) the
      vanadium(IV) ions are well dispersed in the matrix. Varying the vanadium dopant
      concentration within this range or the dopant salt leads to the same dominant EPR
      component. In the ENDOR spectra, hyperfine (HF) interactions with (1) H, (27) Al
      and (51) V nuclei are observed. The HF parameters extracted from simulations
      strongly suggest that the vanadium(IV) ions substitute Al in the framework. 

PMID- 26305911
TI  - Peers, stereotypes and health communication through the cultural lens of
      adolescent Appalachian mothers.
AB  - The purpose of this study was to understand how young Appalachian mothers
      retrospectively construct sexual and reproductive health communication events.
      Sixteen in-depth qualitative interviews were conducted with mothers between the
      ages of 18 and 22 from the South Central Appalachian region of the USA. Findings
      indicate that within this population, peer influence, stereotypes medical
      encounters and formal health education are experienced within a culture that
      exhibits tension between normalising and disparaging adolescent sexuality.
      Theoretical and applied implications acknowledge the role of Appalachian cultural
      values, including egalitarianism, traditional gender roles and fatalism, in
      understanding the social construction of young people's sexuality in this region.
      Practical implications for sexual education and the nature of communication in
      the healthcare setting can be applied to current education curricula and medical
      communication practices. We suggest that future programmes may be more effective
      if they are adapted to the specific culture within which they are taught. 

PMID- 26305913
TI  - Impact of 3D Hierarchical Nanostructures on the Antibacterial Efficacy of a
      Bacteria-Triggered Self-Defensive Antibiotic Coating.
AB  - Titanium is often applied in implant surgery, but frequently implicated in
      infections associated with bacterial adhesion and growth on the implant surface.
      Here, we show that hierarchical nanostructuring of titanium and the subsequent
      coating of resulting topographical features with a self-defensive, antibacterial
      layer-by-layer (LbL) film enables a synergistic action of hierarchical
      nanotopography and localized, bacteria-triggered antibiotic release to
      dramatically enhance the antibacterial efficiency of surfaces. Although sole
      nanostructuring of titanium substrates did not significantly affect adhesion and
      growth of Staphylococcus aureus, the coating of 3D-nanopillared substrates with
      an ultrathin tannic acid/gentamicin (TA/G) LbL film resulted in a 10-fold
      reduction of the number of surface-attached bacteria. This effect is attributed
      to the enlarged surface area of the nanostructured coating available for
      localized bacteria-triggered release of antibiotics, as well as to the lower
      bacterial adhesion forces resulting in subsided activation of bacterial
      antibiotic-defense mechanisms when bacteria land on nanopillar tips. The result
      shows that a combination of 3D nanostructuring with a bacteria-triggered
      antibiotic-releasing coating presents a unique way to dramatically enhance
      antibacterial efficacy of biomaterial implants. 

PMID- 26305912
TI  - Endothelial progenitor cells, defined by the simultaneous surface expression of
      VEGFR2 and CD133, are not detectable in healthy peripheral and cord blood.
AB  - Circulating endothelial cells (CEC) and their progenitors (EPC) are restricted
      subpopulations of peripheral blood (PB), cord blood (CB), and bone marrow (BM)
      cells, involved in the endothelial homeostasis maintenance. Both CEC and EPC are
      thought to represent potential biomarkers in several clinical conditions
      involving endothelial turnover/remodeling. Although different flow cytometry
      methods for CEC and EPC characterization have been published so far, none of them
      have reached consistent conclusions, therefore consensus guidelines with respect
      to CEC and EPC identification and quantification need to be established. Here, we
      have carried out an in depth investigation of CEC and EPC phenotypes in healthy
      PB, CB and BM samples, by optimizing a reliable polychromatic flow cytometry
      (PFC) panel. Results showed that the brightness of CD34 expression on healthy PB
      and CB circulating cells represents a key benchmark for the identification of CEC
      (CD45neg/CD34bright/CD146pos) respect to the hematopoietic stem cell (HSC)
      compartment (CD45dim/CD34pos/CD146neg). This approach, combined with a dual
      platform counting technique, allowed a sharp CEC enumeration in healthy PB (n =
      38), and resulting in consistent CEC counts with previously reported data (median
      = 11.7 cells/ml). In parallel, by using rigorous PFC conditions,
      CD34pos/CD45dim/CD133pos/VEGFR2pos EPC were not found in any healthy PB or CB
      sample, since VEGFR2 expression was never detectable on the surface of
      CD34pos/CD45dim/CD133pos cells. Notably, the putative EPC phenotype was observed
      in all analyzed BM samples (n = 12), and the expression of CD146 and VEGFR2, on
      BM cells, was not restricted to the CD34bright compartment, but also appeared on
      the HSC surface. Altogether, our findings suggest that the previously reported
      EPC antigen profile, defined by the simultaneous expression of VEGFR2 and CD133
      on the surface of CD45dim/CD34pos cells, should be carefully re-evaluated and
      further studies should be conducted to redefine EPC features in order to
      translate CEC and EPC characterization into clinical practice.

PMID- 26305914
TI  - Multidisciplinary assessment measure for individuals with disorders of
      consciousness.
AB  - OBJECTIVE: This study introduces the Comprehensive Assessment Measure for the
      Minimally Responsive Individual (CAMMRI) and reports on its development, inter
      rater reliability, construct validity and clinical value. METHODS: A
      multidisciplinary team of therapists developed this measure, which comprises 12
      sub-tests that examine three main areas: Response to the Environment, Motor
      Control and Communication and Swallowing. The sub-tests are scored using a 7
      point scale; sub-tests can also be administered individually. The measure was
      administered during a pilot project and then 1 year later to 12 adult clients
      with severe acquired brain injury at a long-term rehabilitation programme. The
      age range of the participants was 18-65 years; individuals were 1.5-10 years post
      injury. RESULTS: Comparison measures included the Western Neuro Sensory
      Stimulation Profile (WNSSP), the Coma Recovery Scale-Revised (CRS-R) and the
      Chedoke McMaster Impairment Inventory (CMII). Inter-rater reliability of each sub
      test ranged from 0.87-1.0, with an average of 0.90 in the first year of the
      assessments. CONCLUSION: Validity data supported the use of the CAMMRI for
      minimally conscious adults with ABI to measure behavioural changes and plan
      treatment for this population. Future research should focus on using this measure
      with other neurological populations.

PMID- 26305915
TI  - Synthesis of 4-Arylidenepyrazolones by a Gold-Catalyzed Cyclization/Arylidene
      Group Transfer Cascade of N-Propioloyl Hydrazones.
AB  - An efficient gold-catalyzed cyclization/arylidene group transfer cascade reaction
      of N-propioloyl hydrazones has been developed. This method provides a novel
      approach for the synthesis of various functionalized 4-arylidenepyrazolones. 

PMID- 26305916
TI  - Complete chloroplast genome sequence of green foxtail (Setaria viridis), a
      promising model system for C4 photosynthesis.
AB  - The complete chloroplast genome of green foxtail (Setaria viridis), a promising
      model system for C4 photosynthesis, is first reported in this study. The genome
      harbors a large single copy (LSC) region of 81 016 bp and a small single copy
      (SSC) region of 12 456  bp separated by a pair of inverted repeat (IRa and IRb)
      regions of 22 315 bp. GC content is 38.92%. The proportion of coding sequence is
      57.97%, comprising of 111 (19 duplicated in IR regions) unique genes, 71 of which
      are protein-coding genes, four are rRNA genes, and 36 are tRNA genes.
      Phylogenetic analysis indicated that S. viridis was clustered with its cultivated
      species S. italica in the tribe Paniceae of the family Poaceae. This newly
      determined chloroplast genome will provide valuable genetic resources to assist
      future studies on C4 photosynthesis in grasses.

PMID- 26305918
TI  - A new tubular graphene form of a tetrahedrally connected cellular structure.
AB  - 3D architectures constructed from a tubular graphene network can withstand
      repeated >95% compression cycling without damage. Aided by intertubular covalent
      bonding, this material takes full advantage of the graphene tube's unique
      attributes, including complete pre- and post-buckling elasticity, outstanding
      electrical conductivity, and extraordinary physicochemical stability. A highly
      connected tubular graphene will thus be the ultimate, structurally robust,
      ultrastrong, ultralight material. 

PMID- 26305919
TI  - Comparison of the effects of heparin and the direct factor Xa inhibitor,
      rivaroxaban, on bone microstructure and metabolism in adult rats.
AB  - AIM: Deep venous thrombosis is a significant complication following surgery, and
      is associated with high morbidity and mortality in adults. The direct factor Xa
      inhibitor, rivaroxaban, is used to prevent venous thromboembolism in patients
      suffering from trauma and joint arthroplasty. The present study compared the
      effects of rivaroxaban and heparin on bone microstructure and metabolism in adult
      rats. MATERIALS AND METHODS: Twenty-four Wistar rats were divided into sham,
      rivaroxaban and heparin groups. Rivaroxaban (1.5 mg.kg(-1).d(-1)) and heparin (2
      IU.g(-1).d(-1)) were administered for 4 weeks. To assess changes in bone
      metabolism, serum calcium and phosphorus levels, and bone formation and
      resorption markers were examined. Micro-CT analysis was used to examine the
      microstructure of both trabecular and cortical bone. Dual energy X-ray
      absorptiometry was employed to detect bone mineral density (BMD). RESULTS: Serum
      phosphorus levels were significantly lower in both rivaroxaban (1.33 +/- 0.07
      mmol/L) and heparin (1.33 +/- 0.21 mmol/L) rats than in sham rats (1.71 +/- 0.14
      mmol/L). Activity and levels of bone formation markers, bone-specific alkaline
      phosphatase (BAP) and type I procollagen N-terminal pro-peptide (PINP), were 32.4
      and 38.2% lower in heparin-treated rats than in sham rats. Bone resorption
      markers, pyridinoline (PYD) and deoxypyridinoline (DPD), were 20.1 and 34.3%
      higher in heparin-treated rats than in sham rats, respectively. By contrast,
      rivaroxaban only resulted in a decrease PINP levels. Bone volume fraction (BV/TV)
      decreased by 23.5 and 20.5% from those in sham rats, while trabecular separation
      (Tb.Sp) increased by 28.2 and 16.3% in trabecular bone of heparin- and
      rivaroxaban-treated rats, [corrected] respectively. Moreover, the microstructure
      of cortical bone and BMD were negatively affected by heparin but not by
      rivaroxaban. CONCLUSION: Rivaroxaban leads to fewer adverse effects on bone
      microstructure than heparin.

PMID- 26305917
TI  - Analysis of different HER-2 mutations in breast cancer progression and drug
      resistance.
AB  - Studies over the last two decades have identified that amplified human epidermal
      growth factor receptor (HER-2; c-erbB-2, neu) and its overexpression have been
      frequently implicated in the carcinogenesis and prognosis in a variety of solid
      tumours, especially breast cancer. Lots of painstaking efforts were invested on
      the HER-2 targeted agents, and significantly improved outcome and prolonged the
      survival of patients. However, some patients classified as 'HER-2-positive' would
      be still resistant to the anti-HER-2 therapy. Various mechanisms of drug
      resistance have been illustrated and the alteration of HER-2 was considered as a
      crucial mechanism. However, systematic researches in regard to the HER-2
      mutations and variants are still inadequate. Notably, the alterations of HER-2
      play an important role in drug resistance, but also have a potential association
      with the cancer risk. In this review, we summarize the possible mutations and
      focus on HER-2 variants' role in breast cancer tumourigenesis. Additionally, the
      alteration of HER-2, as a potential mechanism of resistance to trastuzumab, is
      discussed here. We hope that HER-2 related activating mutations could potentially
      offer more therapeutic opportunities to a broader range of patients than
      previously classified as HER-2 overexpressed. 

PMID- 26305921
TI  - An examination of three theoretical models to explain the organ donation attitude
      -registration discrepancy among mature adults.
AB  - An inconsistency in the research indicates positive attitudes toward organ
      donation do not map reliably onto organ donor registrations. Various models have
      sought to explain this inconsistency and the current analysis formally compared
      three models: the Bystander Intervention Model (BIM), the Organ Donor Model
      (ODM), and Vested Interest Theory (VIT). Mature (N = 688) adults between the ages
      of 50 to 64 years completed surveys related to organ donation. Results revealed
      that VIT accounted for the most variance in organ donation registrations followed
      by the BIM and ODM. The discussion emphasizes the importance of employing
      theories to explain a phenomenon as well as the practical implications of the
      findings. 

PMID- 26305922
TI  - Editorial Notice.

PMID- 26305924
TI  - Introduction to Fifth Special Issue on Electroporation-Based Technologies and
      Treatments.

PMID- 26305923
TI  - Dysfunction of Rice Mitochondrial Membrane Induced by Yb3+.
AB  - Ytterbium (Yb), a widely used rare earth element, is treated as highly toxic to
      human being and adverseness to plant. Mitochondria play a significant role in
      plant growth and development, and are proposed as a potential target for
      ytterbium toxicity. In this paper, the biological effect of Yb(3+) on isolated
      rice mitochondria was investigated. We found that Yb(3+) with high concentrations
      (200 ~ 600 MUM) not only induced mitochondrial membrane permeability transition
      (mtMPT), but also disturbed the mitochondrial ultrastructure. Moreover, Yb(3+)
      caused the respiratory chain damage, ROS formation, membrane potential decrease,
      and mitochondrial complex II activity reverse. The results above suggested that
      Yb(3+) with high concentrations could induce mitochondrial membrane dysfunction.
      These findings will support some valuable information to the safe application of
      Yb-based agents.

PMID- 26305925
TI  - Two methods for estimating limits to large-scale wind power generation.
AB  - Wind turbines remove kinetic energy from the atmospheric flow, which reduces wind
      speeds and limits generation rates of large wind farms. These interactions can be
      approximated using a vertical kinetic energy (VKE) flux method, which predicts
      that the maximum power generation potential is 26% of the instantaneous downward
      transport of kinetic energy using the preturbine climatology. We compare the
      energy flux method to the Weather Research and Forecasting (WRF) regional
      atmospheric model equipped with a wind turbine parameterization over a 10(5) km2
      region in the central United States. The WRF simulations yield a maximum
      generation of 1.1 We?m(-2), whereas the VKE method predicts the time series while
      underestimating the maximum generation rate by about 50%. Because VKE derives the
      generation limit from the preturbine climatology, potential changes in the
      vertical kinetic energy flux from the free atmosphere are not considered. Such
      changes are important at night when WRF estimates are about twice the VKE value
      because wind turbines interact with the decoupled nocturnal low-level jet in this
      region. Daytime estimates agree better to 20% because the wind turbines induce
      comparatively small changes to the downward kinetic energy flux. This combination
      of downward transport limits and wind speed reductions explains why large-scale
      wind power generation in windy regions is limited to about 1 We?m(-2), with VKE
      capturing this combination in a comparatively simple way.

PMID- 26305926
TI  - The COUP-TFII/Neuropilin-2 is a molecular switch steering diencephalon-derived
      GABAergic neurons in the developing mouse brain.
AB  - The preoptic area (POa) of the rostral diencephalon supplies the neocortex and
      the amygdala with GABAergic neurons in the developing mouse brain. However, the
      molecular mechanisms that determine the pathway and destinations of POa-derived
      neurons have not yet been identified. Here we show that Chicken ovalbumin
      upstream promoter transcription factor II (COUP-TFII)-induced expression of
      Neuropilin-2 (Nrp2) and its down-regulation control the destination of POa
      derived GABAergic neurons. Initially, a majority of the POa-derived migrating
      neurons express COUP-TFII and form a caudal migratory stream toward the caudal
      subpallium. When a subpopulation of cells steers toward the neocortex, they
      exhibit decreased expression of COUP-TFII and Nrp2. The present findings show
      that suppression of COUP-TFII/Nrp2 changed the destination of the cells into the
      neocortex, whereas overexpression of COUP-TFII/Nrp2 caused cells to end up in the
      medial part of the amygdala. Taken together, these results reveal that COUP
      TFII/Nrp2 is a molecular switch determining the pathway and destination of
      migrating GABAergic neurons born in the POa. 

PMID- 26305927
TI  - An architecture for encoding sentence meaning in left mid-superior temporal
      cortex.
AB  - Human brains flexibly combine the meanings of words to compose structured
      thoughts. For example, by combining the meanings of "bite," "dog," and "man," we
      can think about a dog biting a man, or a man biting a dog. Here, in two
      functional magnetic resonance imaging (fMRI) experiments using multivoxel pattern
      analysis (MVPA), we identify a region of left mid-superior temporal cortex
      (lmSTC) that flexibly encodes "who did what to whom" in visually presented
      sentences. We find that lmSTC represents the current values of abstract semantic
      variables ("Who did it?" and "To whom was it done?") in distinct subregions.
      Experiment 1 first identifies a broad region of lmSTC whose activity patterns (i)
      facilitate decoding of structure-dependent sentence meaning ("Who did what to
      whom?") and (ii) predict affect-related amygdala responses that depend on this
      information (e.g., "the baby kicked the grandfather" vs. "the grandfather kicked
      the baby"). Experiment 2 then identifies distinct, but neighboring, subregions of
      lmSTC whose activity patterns carry information about the identity of the current
      "agent" ("Who did it?") and the current "patient" ("To whom was it done?"). These
      neighboring subregions lie along the upper bank of the superior temporal sulcus
      and the lateral bank of the superior temporal gyrus, respectively. At a high
      level, these regions may function like topographically defined data registers,
      encoding the fluctuating values of abstract semantic variables. This functional
      architecture, which in key respects resembles that of a classical computer, may
      play a critical role in enabling humans to flexibly generate complex thoughts. 

PMID- 26305928
TI  - Oligoribonuclease is a central feature of cyclic diguanylate signaling in
      Pseudomonas aeruginosa.
AB  - The second messenger cyclic diguanylate (c-di-GMP) controls diverse cellular
      processes among bacteria. Diguanylate cyclases synthesize c-di-GMP, whereas it is
      degraded by c-di-GMP-specific phosphodiesterases (PDEs). Nearly 80% of these PDEs
      are predicted to depend on the catalytic function of glutamate-alanine-leucine
      (EAL) domains, which hydrolyze a single phosphodiester group in c-di-GMP to
      produce 5'-phosphoguanylyl-(3',5')-guanosine (pGpG). However, to degrade pGpG and
      prevent its accumulation, bacterial cells require an additional nuclease, the
      identity of which remains unknown. Here we identify oligoribonuclease (Orn)-a 3'
      >5' exonuclease highly conserved among Actinobacteria, Beta-, Delta- and
      Gammaproteobacteria-as the primary enzyme responsible for pGpG degradation in
      Pseudomonas aeruginosa cells. We found that a P. aeruginosa Deltaorn mutant had
      high intracellular c-di-GMP levels, causing this strain to overexpress
      extracellular polymers and overproduce biofilm. Although recombinant Orn degraded
      small RNAs in vitro, this enzyme had a proclivity for degrading RNA oligomers
      comprised of two to five nucleotides (nanoRNAs), including pGpG. Corresponding
      with this activity, Deltaorn cells possessed highly elevated pGpG levels. We
      found that pGpG reduced the rate of c-di-GMP degradation in cell lysates and
      inhibited the activity of EAL-dependent PDEs (PA2133, PvrR, and purified
      recombinant RocR) from P. aeruginosa. This pGpG-dependent inhibition was
      alleviated by the addition of Orn. These data suggest that elevated levels of
      pGpG exert product inhibition on EAL-dependent PDEs, thereby increasing
      intracellular c-di-GMP in Deltaorn cells. Thus, we propose that Orn provides
      homeostatic control of intracellular pGpG under native physiological conditions
      and that this activity is fundamental to c-di-GMP signal transduction. 

PMID- 26305929
TI  - Neural coding underlying the cue preference for celestial orientation.
AB  - Diurnal and nocturnal African dung beetles use celestial cues, such as the sun,
      the moon, and the polarization pattern, to roll dung balls along straight paths
      across the savanna. Although nocturnal beetles move in the same manner through
      the same environment as their diurnal relatives, they do so when light conditions
      are at least 1 million-fold dimmer. Here, we show, for the first time to our
      knowledge, that the celestial cue preference differs between nocturnal and
      diurnal beetles in a manner that reflects their contrasting visual ecologies. We
      also demonstrate how these cue preferences are reflected in the activity of
      compass neurons in the brain. At night, polarized skylight is the dominant
      orientation cue for nocturnal beetles. However, if we coerce them to roll during
      the day, they instead use a celestial body (the sun) as their primary orientation
      cue. Diurnal beetles, however, persist in using a celestial body for their
      compass, day or night. Compass neurons in the central complex of diurnal beetles
      are tuned only to the sun, whereas the same neurons in the nocturnal species
      switch exclusively to polarized light at lunar light intensities. Thus, these
      neurons encode the preferences for particular celestial cues and alter their
      weighting according to ambient light conditions. This flexible encoding of
      celestial cue preferences relative to the prevailing visual scenery provides a
      simple, yet effective, mechanism for enabling visual orientation at any light
      intensity. 

PMID- 26305930
TI  - Mechanical control of mitotic progression in single animal cells.
AB  - Despite the importance of mitotic cell rounding in tissue development and cell
      proliferation, there remains a paucity of approaches to investigate the
      mechanical robustness of cell rounding. Here we introduce ion beam-sculpted
      microcantilevers that enable precise force-feedback-controlled confinement of
      single cells while characterizing their progression through mitosis. We identify
      three force regimes according to the cell response: small forces (~5 nN) that
      accelerate mitotic progression, intermediate forces where cells resist
      confinement (50-100 nN), and yield forces (>100 nN) where a significant decline
      in cell height impinges on microtubule spindle function, thereby inhibiting
      mitotic progression. Yield forces are coincident with a nonlinear drop in cell
      height potentiated by persistent blebbing and loss of cortical F-actin
      homogeneity. Our results suggest that a buildup of actomyosin-dependent cortical
      tension and intracellular pressure precedes mechanical failure, or herniation, of
      the cell cortex at the yield force. Thus, we reveal how the mechanical properties
      of mitotic cells and their response to external forces are linked to mitotic
      progression under conditions of mechanical confinement. 

PMID- 26305931
TI  - Telomerase RNA stem terminus element affects template boundary element function,
      telomere sequence, and shelterin binding.
AB  - The stem terminus element (STE), which was discovered 13 y ago in human
      telomerase RNA, is required for telomerase activity, yet its mode of action is
      unknown. We report that the Schizosaccharomyces pombe telomerase RNA, TER1
      (telomerase RNA 1), also contains a STE, which is essential for telomere
      maintenance. Cells expressing a partial loss-of-function TER1 STE allele
      maintained short stable telomeres by a recombination-independent mechanism.
      Remarkably, the mutant telomere sequence was different from that of wild-type
      cells. Generation of the altered sequence is explained by reverse transcription
      into the template boundary element, demonstrating that the STE helps maintain
      template boundary element function. The altered telomeres bound less Pot1
      (protection of telomeres 1) and Taz1 (telomere-associated in Schizosaccharomyces
      pombe 1) in vivo. Thus, the S. pombe STE, although distant from the template,
      ensures proper telomere sequence, which in turn promotes proper assembly of the
      shelterin complex. 

PMID- 26305932
TI  - Fungal biosynthesis of the bibenzoquinone oosporein to evade insect immunity.
AB  - Quinones are widely distributed in nature and exhibit diverse biological or
      pharmacological activities; however, their biosynthetic machineries are largely
      unknown. The bibenzoquinone oosporein was first identified from the ascomycete
      insect pathogen Beauveria bassiana>50 y ago. The toxin can also be produced by
      different plant pathogenic and endophytic fungi with an array of biological
      activities. Here, we report the oosporein biosynthetic machinery in fungi, a
      polyketide synthase (PKS) pathway including seven genes for quinone biosynthesis.
      The PKS oosporein synthase 1 (OpS1) produces orsellinic acid that is hydroxylated
      to benzenetriol by the hydroxylase OpS4. The intermediate is oxidized either
      nonenzymatically to 5,5'-dideoxy-oosporein or enzymatically to benzenetetrol by
      the putative dioxygenase OpS7. The latter is further dimerized to oosporein by
      the catalase OpS5. The transcription factor OpS3 regulates intrapathway gene
      expression. Insect bioassays revealed that oosporein is required for fungal
      virulence and acts by evading host immunity to facilitate fungal multiplication
      in insects. These results contribute to the known mechanisms of quinone
      biosynthesis and the understanding of small molecules deployed by fungi that
      interact with their hosts.

PMID- 26305933
TI  - Genome-wide RNAi screening identifies host restriction factors critical for in
      vivo AAV transduction.
AB  - Viral vectors based on the adeno-associated virus (AAV) hold great promise for in
      vivo gene transfer; several unknowns, however, still limit the vectors' broader
      and more efficient application. Here, we report the results of a high-throughput,
      whole-genome siRNA screening aimed at identifying cellular factors regulating AAV
      transduction. We identified 1,483 genes affecting vector efficiency more than 4
      fold and up to 50-fold, either negatively or positively. Most of these factors
      have not previously been associated to AAV infection. The most effective siRNAs
      were independent from the virus serotype or analyzed cell type and were equally
      evident for single-stranded and self-complementary AAV vectors. A common
      characteristic of the most effective siRNAs was the induction of cellular DNA
      damage and activation of a cell cycle checkpoint. This information can be
      exploited for the development of more efficient AAV-based gene delivery
      procedures. Administration of the most effective siRNAs identified by the
      screening to the liver significantly improved in vivo AAV transduction
      efficiency. 

PMID- 26305934
TI  - Tectonics, climate, and the rise and demise of continental aquatic species
      richness hotspots.
AB  - Continental aquatic species richness hotspots are unevenly distributed across the
      planet. In present-day Europe, only two centers of biodiversity exist (Lake Ohrid
      on the Balkans and the Caspian Sea). During the Neogene, a wide variety of
      hotspots developed in a series of long-lived lakes. The mechanisms underlying the
      presence of richness hotspots in different geological periods have not been
      properly examined thus far. Based on Miocene to Recent gastropod distributions,
      we show that the existence and evolution of such hotspots in inland-water systems
      are tightly linked to the geodynamic history of the European continent. Both past
      and present hotspots are related to the formation and persistence of long-lived
      lake systems in geological basins or to isolation of existing inland basins and
      embayments from the marine realm. The faunal evolution within hotspots highly
      depends on warm climates and surface area. During the Quaternary icehouse climate
      and extensive glaciations, limnic biodiversity sustained a severe decline across
      the continent and most former hotspots disappeared. The Recent gastropod
      distribution is mainly a geologically young pattern formed after the Last Glacial
      Maximum (19 ky) and subsequent formation of postglacial lakes. The major hotspots
      today are related to long-lived lakes in preglacially formed, permanently
      subsiding geological basins. 

PMID- 26305935
TI  - RGS9-2--controlled adaptations in the striatum determine the onset of action and
      efficacy of antidepressants in neuropathic pain states.
AB  - The striatal protein Regulator of G-protein signaling 9-2 (RGS9-2) plays a key
      modulatory role in opioid, monoamine, and other G-protein-coupled receptor
      responses. Here, we use the murine spared-nerve injury model of neuropathic pain
      to investigate the mechanism by which RGS9-2 in the nucleus accumbens (NAc), a
      brain region involved in mood, reward, and motivation, modulates the actions of
      tricyclic antidepressants (TCAs). Prevention of RGS9-2 action in the NAc
      increases the efficacy of the TCA desipramine and dramatically accelerates its
      onset of action. By controlling the activation of effector molecules by G protein
      alpha and betagamma subunits, RGS9-2 affects several protein interactions,
      phosphoprotein levels, and the function of the epigenetic modifier histone
      deacetylase 5, which are important for TCA responsiveness. Furthermore,
      information from RNA-sequencing analysis reveals that RGS9-2 in the NAc affects
      the expression of many genes known to be involved in nociception, analgesia, and
      antidepressant drug actions. Our findings provide novel information on NAc
      specific cellular mechanisms that mediate the actions of TCAs in neuropathic pain
      states. 

PMID- 26305936
TI  - Cohesin recruits the Esco1 acetyltransferase genome wide to repress transcription
      and promote cohesion in somatic cells.
AB  - The cohesin complex links DNA molecules and plays key roles in the organization,
      expression, repair, and segregation of eukaryotic genomes. In vertebrates the
      Esco1 and Esco2 acetyltransferases both modify cohesin's Smc3 subunit to
      establish sister chromatid cohesion during S phase, but differ in their N
      terminal domains and expression during development and across the cell cycle.
      Here we show that Esco1 and Esco2 also differ dramatically in their interaction
      with chromatin, as Esco1 is recruited by cohesin to over 11,000 sites, whereas
      Esco2 is infrequently enriched at REST/NRSF target genes. Esco1's colocalization
      with cohesin occurs throughout the cell cycle and depends on two short motifs
      (the A-box and B-box) present in and unique to all Esco1 orthologs. Deleting
      either motif led to the derepression of Esco1-proximal genes and functional
      uncoupling of cohesion from Smc3 acetylation. In contrast, other mutations that
      preserved Esco1's recruitment separated its roles in cohesion establishment and
      gene silencing. We conclude that Esco1 uses cohesin as both a substrate and a
      scaffold for coordinating multiple chromatin-based transactions in somatic cells.

PMID- 26305937
TI  - Fate of a mutation in a fluctuating environment.
AB  - Natural environments are never truly constant, but the evolutionary implications
      of temporally varying selection pressures remain poorly understood. Here we
      investigate how the fate of a new mutation in a fluctuating environment depends
      on the dynamics of environmental variation and on the selective pressures in each
      condition. We find that even when a mutation experiences many environmental
      epochs before fixing or going extinct, its fate is not necessarily determined by
      its time-averaged selective effect. Instead, environmental variability reduces
      the efficiency of selection across a broad parameter regime, rendering selection
      unable to distinguish between mutations that are substantially beneficial and
      substantially deleterious on average. Temporal fluctuations can also dramatically
      increase fixation probabilities, often making the details of these fluctuations
      more important than the average selection pressures acting on each new mutation.
      For example, mutations that result in a trade-off between conditions but are
      strongly deleterious on average can nevertheless be more likely to fix than
      mutations that are always neutral or beneficial. These effects can have important
      implications for patterns of molecular evolution in variable environments, and
      they suggest that it may often be difficult for populations to maintain
      specialist traits, even when their loss leads to a decline in time-averaged
      fitness. 

PMID- 26305939
TI  - A parthenogenesis gene of apomict origin elicits embryo formation from
      unfertilized eggs in a sexual plant.
AB  - Apomixis is a naturally occurring mode of asexual reproduction in flowering
      plants that results in seed formation without the involvement of meiosis or
      fertilization of the egg. Seeds formed on an apomictic plant contain offspring
      genetically identical to the maternal plant. Apomixis has significant potential
      for preserving hybrid vigor from one generation to the next in highly productive
      crop plant genotypes. Apomictic Pennisetum/Cenchrus species, members of the
      Poaceae (grass) family, reproduce by apospory. Apospory is characterized by
      apomeiosis, the formation of unreduced embryo sacs derived from nucellar cells of
      the ovary and, by parthenogenesis, the development of the unreduced egg into an
      embryo without fertilization. In Pennisetum squamulatum (L.) R.Br., apospory
      segregates as a single dominant locus, the apospory-specific genomic region
      (ASGR). In this study, we demonstrate that the PsASGR-BABY BOOM-like (PsASGR
      BBML) gene is expressed in egg cells before fertilization and can induce
      parthenogenesis and the production of haploid offspring in transgenic sexual
      pearl millet. A reduction of PsASGR-BBML expression in apomictic F1 RNAi
      transgenic plants results in fewer visible parthenogenetic embryos and a
      reduction of embryo cell number compared with controls. Our results endorse a key
      role for PsASGR-BBML in parthenogenesis and a newly discovered role for a member
      of the BBM-like clade of APETALA 2 transcription factors. Induction of
      parthenogenesis by PsASGR-BBML will be valuable for installing parthenogenesis to
      synthesize apomixis in crops and will have further application for haploid
      induction to rapidly obtain homozygous lines for breeding. 

PMID- 26305938
TI  - Native root-associated bacteria rescue a plant from a sudden-wilt disease that
      emerged during continuous cropping.
AB  - Plants maintain microbial associations whose functions remain largely unknown.
      For the past 15 y, we have planted the annual postfire tobacco Nicotiana
      attenuata into an experimental field plot in the plant's native habitat, and for
      the last 8 y the number of plants dying from a sudden wilt disease has increased,
      leading to crop failure. Inadvertently we had recapitulated the common
      agricultural dilemma of pathogen buildup associated with continuous cropping for
      this native plant. Plants suffered sudden tissue collapse and black roots,
      symptoms similar to a Fusarium-Alternaria disease complex, recently characterized
      in a nearby native population and developed into an in vitro pathosystem for N.
      attenuata. With this in vitro disease system, different protection strategies
      (fungicide and inoculations with native root-associated bacterial and fungal
      isolates), together with a biochar soil amendment, were tested further in the
      field. A field trial with more than 900 plants in two field plots revealed that
      inoculation with a mixture of native bacterial isolates significantly reduced
      disease incidence and mortality in the infected field plot without influencing
      growth, herbivore resistance, or 32 defense and signaling metabolites known to
      mediate resistance against native herbivores. Tests in a subsequent year revealed
      that a core consortium of five bacteria was essential for disease reduction. This
      consortium, but not individual members of the root-associated bacteria community
      which this plant normally recruits during germination from native seed banks,
      provides enduring resistance against fungal diseases, demonstrating that native
      plants develop opportunistic mutualisms with prokaryotes that solve context
      dependent ecological problems. 

PMID- 26305940
TI  - Allosteric activation of apicomplexan calcium-dependent protein kinases.
AB  - Calcium-dependent protein kinases (CDPKs) comprise the major group of Ca2+
      regulated kinases in plants and protists. It has long been assumed that CDPKs are
      activated, like other Ca2+-regulated kinases, by derepression of the kinase
      domain (KD). However, we found that removal of the autoinhibitory domain from
      Toxoplasma gondii CDPK1 is not sufficient for kinase activation. From a library
      of heavy chain-only antibody fragments (VHHs), we isolated an antibody (1B7) that
      binds TgCDPK1 in a conformation-dependent manner and potently inhibits it. We
      uncovered the molecular basis for this inhibition by solving the crystal
      structure of the complex and simulating, through molecular dynamics, the effects
      of 1B7-kinase interactions. In contrast to other Ca2+-regulated kinases, the
      regulatory domain of TgCDPK1 plays a dual role, inhibiting or activating the
      kinase in response to changes in Ca2+ concentrations. We propose that the
      regulatory domain of TgCDPK1 acts as a molecular splint to stabilize the
      otherwise inactive KD. This dependence on allosteric stabilization reveals a
      novel susceptibility in this important class of parasite enzymes.

PMID- 26305941
TI  - IFN-gamma ameliorates autoimmune encephalomyelitis by limiting myelin lipid
      peroxidation.
AB  - Evidence has suggested both a pathogenic and a protective role for the
      proinflammatory cytokine IFN-gamma in experimental autoimmune encephalomyelitis
      (EAE). However, the mechanisms underlying the protective role of IFN-gamma in EAE
      have not been fully resolved, particularly in the context of CNS antigen
      presenting cells (APCs). In this study we examined the role of IFN-gamma in
      myelin antigen uptake by CNS APCs during EAE. We found that myelin antigen
      colocalization with APCs was decreased substantially and that EAE was
      significantly more severe and showed a chronic-progressive course in IFN-gamma
      knockout (IFN-gamma-/-) or IFN-gamma receptor knockout (IFN-gammaR-/-) mice as
      compared with WT animals. IFN-gamma was a critical regulator of
      phagocytic/activating receptors on CNS APCs. Importantly, "free" myelin debris
      and lipid peroxidation activity at CNS lesions was increased in mice lacking IFN
      gamma signaling. Treatment with N-acetyl-l-cysteine, a potent antioxidant,
      abolished lipid peroxidation activity and ameliorated EAE in IFN-gamma-signaling
      deficient mice. Taken together the data suggest a protective role for IFN-gamma
      in EAE by regulating the removal of myelin debris by CNS APCs and thereby
      limiting the substrate available for the generation of neurotoxic lipid
      peroxidation products.

PMID- 26305942
TI  - Subset of early radial glial progenitors that contribute to the development of
      callosal neurons is absent from avian brain.
AB  - The classical view of mammalian cortical development suggests that pyramidal
      neurons are generated in a temporal sequence, with all radial glial cells (RGCs)
      contributing to both lower and upper neocortical layers. A recent opposing
      proposal suggests there is a subgroup of fate-restricted RGCs in the early
      neocortex, which generates only upper-layer neurons. Little is known about the
      existence of fate restriction of homologous progenitors in other vertebrate
      species. We investigated the lineage of selected Emx2+ [vertebrate homeobox gene
      related to Drosophila empty spiracles (ems)] RGCs in mouse neocortex and chick
      forebrain and found evidence for both sequential and fate-restricted programs
      only in mouse, indicating that these complementary populations coexist in the
      developing mammalian but not avian brain. Among a large population of
      sequentially programmed RGCs in the mouse brain, a subset of self-renewing
      progenitors lack neurogenic potential during the earliest phase of
      corticogenesis. After a considerable delay, these progenitors generate callosal
      upper-layer neurons and glia. On the other hand, we found no homologous delayed
      population in any sectors of the chick forebrain. This finding suggests that
      neurogenic delay of selected RGCs may be unique to mammals and possibly
      associated with the evolution of the corpus callosum.

PMID- 26305943
TI  - Provirophages in the Bigelowiella genome bear testimony to past encounters with
      giant viruses.
AB  - Virophages are recently discovered double-stranded DNA virus satellites that prey
      on giant viruses (nucleocytoplasmic large DNA viruses; NCLDVs), which are
      themselves parasites of unicellular eukaryotes. This coupled parasitism can
      result in the indirect control of eukaryotic cell mortality by virophages.
      However, the details of such tripartite relationships remain largely unexplored.
      We have discovered ~300 predicted genes of putative virophage origin in the
      nuclear genome of the unicellular alga Bigelowiella natans. Physical clustering
      of these genes indicates that virophage genomes are integrated into the B. natans
      genome. Virophage inserts show high levels of similarity and synteny between each
      other, indicating that they are closely related. Virophage genes are transcribed
      not only in the sequenced B. natans strain but also in other Bigelowiella
      isolates, suggesting that transcriptionally active virophage inserts are
      widespread in Bigelowiella populations. Evidence that B. natans is also a host to
      NCLDV members is provided by the identification of NCLDV inserts in its genome.
      These putative large DNA viruses may be infected by B. natans virophages. We also
      identify four repeated elements sharing structural and genetic similarities with
      transpovirons--a class of mobile elements first discovered in giant viruses--that
      were probably independently inserted in the B. natans genome. We argue that
      endogenized provirophages may be beneficial to both the virophage and B. natans
      by (i) increasing the chances for the virophage to coinfect the host cell with an
      NCLDV prey and (ii) defending the host cell against fatal NCLDV infections.

PMID- 26305946
TI  - Instability of thermoremanence and the problem of estimating the ancient
      geomagnetic field strength from non-single-domain recorders.
AB  - Data on the past intensity of Earth's magnetic field (paleointensity) are
      essential for understanding Earth's deep interior, climatic modeling, and
      geochronology applications, among other items. Here we demonstrate the
      possibility that much of available paleointensity data could be biased by
      instability of thermoremanent magnetization (TRM) associated with non-single
      domain (SD) particles. Paleointensity data are derived from experiments in which
      an ancient TRM, acquired in an unknown field, is replaced by a laboratory
      controlled TRM. This procedure is built on the assumption that the process of
      ancient TRM acquisition is entirely reproducible in the laboratory. Here we show
      experimental results violating this assumption in a manner not expected from
      standard theory. We show that the demagnetization-remagnetization relationship of
      non-SD specimens that were kept in a controlled field for only 2 y show a small
      but systematic bias relative to sister specimens that were given a fresh TRM.
      This effect, likely caused by irreversible changes in micromagnetic structures,
      leads to a bias in paleointensity estimates. 

PMID- 26305944
TI  - Expanded metabolic versatility of ubiquitous nitrite-oxidizing bacteria from the
      genus Nitrospira.
AB  - Nitrospira are a diverse group of nitrite-oxidizing bacteria and among the
      environmentally most widespread nitrifiers. However, they remain scarcely studied
      and mostly uncultured. Based on genomic and experimental data from Nitrospira
      moscoviensis representing the ubiquitous Nitrospira lineage II, we identified
      ecophysiological traits that contribute to the ecological success of Nitrospira.
      Unexpectedly, N. moscoviensis possesses genes coding for a urease and cleaves
      urea to ammonia and CO2. Ureolysis was not observed yet in nitrite oxidizers and
      enables N. moscoviensis to supply ammonia oxidizers lacking urease with ammonia
      from urea, which is fully nitrified by this consortium through reciprocal
      feeding. The presence of highly similar urease genes in Nitrospira lenta from
      activated sludge, in metagenomes from soils and freshwater habitats, and of other
      ureases in marine nitrite oxidizers, suggests a wide distribution of this
      extended interaction between ammonia and nitrite oxidizers, which enables nitrite
      oxidizing bacteria to indirectly use urea as a source of energy. A soluble
      formate dehydrogenase lends additional ecophysiological flexibility and allows N.
      moscoviensis to use formate, with or without concomitant nitrite oxidation, using
      oxygen, nitrate, or both compounds as terminal electron acceptors. Compared with
      Nitrospira defluvii from lineage I, N. moscoviensis shares the Nitrospira core
      metabolism but shows substantial genomic dissimilarity including genes for
      adaptations to elevated oxygen concentrations. Reciprocal feeding and metabolic
      versatility, including the participation in different nitrogen cycling processes,
      likely are key factors for the niche partitioning, the ubiquity, and the high
      diversity of Nitrospira in natural and engineered ecosystems. 

PMID- 26305945
TI  - Oligoribonuclease is the primary degradative enzyme for pGpG in Pseudomonas
      aeruginosa that is required for cyclic-di-GMP turnover.
AB  - The bacterial second messenger cyclic di-GMP (c-di-GMP) controls biofilm
      formation and other phenotypes relevant to pathogenesis. Cyclic-di-GMP is
      synthesized by diguanylate cyclases (DGCs). Phosphodiesterases (PDE-As) end
      signaling by linearizing c-di-GMP to 5'-phosphoguanylyl-(3',5')-guanosine (pGpG),
      which is then hydrolyzed to two GMP molecules by yet unidentified enzymes termed
      PDE-Bs. We show that pGpG inhibits a PDE-A from Pseudomonas aeruginosa. In a dual
      DGC and PDE-A reaction, excess pGpG extends the half-life of c-di-GMP, indicating
      that removal of pGpG is critical for c-di-GMP homeostasis. Thus, we sought to
      identify the PDE-B enzyme(s) responsible for pGpG degradation. A differential
      radial capillary action of ligand assay-based screen for pGpG binding proteins
      identified oligoribonuclease (Orn), an exoribonuclease that hydrolyzes two- to
      five-nucleotide-long RNAs. Purified Orn rapidly converts pGpG into GMP. To
      determine whether Orn is the primary enzyme responsible for degrading pGpG, we
      assayed cell lysates of WT and ?orn strains of P. aeruginosa PA14 for pGpG
      stability. The lysates from ?orn showed 25-fold decrease in pGpG hydrolysis.
      Complementation with WT, but not active site mutants, restored hydrolysis.
      Accumulation of pGpG in the ?orn strain could inhibit PDE-As, increasing c-di-GMP
      concentration. In support, we observed increased transcription from the c-di-GMP
      regulated pel promoter. Additionally, the c-di-GMP-governed auto-aggregation and
      biofilm phenotypes were elevated in the ?orn strain in a pel-dependent manner.
      Finally, we directly detect elevated pGpG and c-di-GMP in the ?orn strain. Thus,
      we identified that Orn serves as the primary PDE-B enzyme that removes pGpG,
      which is necessary to complete the final step in the c-di-GMP degradation
      pathway. 

PMID- 26305947
TI  - Hybrid bioinorganic approach to solar-to-chemical conversion.
AB  - Natural photosynthesis harnesses solar energy to convert CO2 and water to value
      added chemical products for sustaining life. We present a hybrid bioinorganic
      approach to solar-to-chemical conversion in which sustainable electrical and/or
      solar input drives production of hydrogen from water splitting using
      biocompatible inorganic catalysts. The hydrogen is then used by living cells as a
      source of reducing equivalents for conversion of CO2 to the value-added chemical
      product methane. Using platinum or an earth-abundant substitute, alpha-NiS, as
      biocompatible hydrogen evolution reaction (HER) electrocatalysts and
      Methanosarcina barkeri as a biocatalyst for CO2 fixation, we demonstrate robust
      and efficient electrochemical CO2 to CH4 conversion at up to 86% overall Faradaic
      efficiency for >= 7 d. Introduction of indium phosphide photocathodes and
      titanium dioxide photoanodes affords a fully solar-driven system for methane
      generation from water and CO2, establishing that compatible inorganic and
      biological components can synergistically couple light-harvesting and catalytic
      functions for solar-to-chemical conversion.

PMID- 26305948
TI  - Structural basis of antizyme-mediated regulation of polyamine homeostasis.
AB  - Polyamines are organic polycations essential for cell growth and differentiation;
      their aberrant accumulation is often associated with diseases, including many
      types of cancer. To maintain polyamine homeostasis, the catalytic activity and
      protein abundance of ornithine decarboxylase (ODC), the committed enzyme for
      polyamine biosynthesis, are reciprocally controlled by the regulatory proteins
      antizyme isoform 1 (Az1) and antizyme inhibitor (AzIN). Az1 suppresses polyamine
      production by inhibiting the assembly of the functional ODC homodimer and, most
      uniquely, by targeting ODC for ubiquitin-independent proteolytic destruction by
      the 26S proteasome. In contrast, AzIN positively regulates polyamine levels by
      competing with ODC for Az1 binding. The structural basis of the Az1-mediated
      regulation of polyamine homeostasis has remained elusive. Here we report crystal
      structures of human Az1 complexed with either ODC or AzIN. Structural analysis
      revealed that Az1 sterically blocks ODC homodimerization. Moreover, Az1 binding
      triggers ODC degradation by inducing the exposure of a cryptic proteasome
      interacting surface of ODC, which illustrates how a substrate protein may be
      primed upon association with Az1 for ubiquitin-independent proteasome
      recognition. Dynamic and functional analyses further indicated that the Az1
      induced binding and degradation of ODC by proteasome can be decoupled, with the
      intrinsically disordered C-terminal tail fragment of ODC being required only for
      degradation but not binding. Finally, the AzIN-Az1 structure suggests how AzIN
      may effectively compete with ODC for Az1 to restore polyamine production. Taken
      together, our findings offer structural insights into the Az-mediated regulation
      of polyamine homeostasis and proteasomal degradation. 

PMID- 26305949
TI  - Bacterial SPOR domains are recruited to septal peptidoglycan by binding to glycan
      strands that lack stem peptides.
AB  - Bacterial SPOR domains bind peptidoglycan (PG) and are thought to target proteins
      to the cell division site by binding to "denuded" glycan strands that lack stem
      peptides, but uncertainties remain, in part because septal-specific binding has
      yet to be studied in a purified system. Here we show that fusions of GFP to SPOR
      domains from the Escherichia coli cell-division proteins DamX, DedD, FtsN, and
      RlpA all localize to septal regions of purified PG sacculi obtained from E. coli
      and Bacillus subtilis. Treatment of sacculi with an amidase that removes stem
      peptides enhanced SPOR domain binding, whereas treatment with a lytic
      transglycosylase that removes denuded glycans reduced SPOR domain binding. These
      findings demonstrate unequivocally that SPOR domains localize by binding to
      septal PG, that the physiologically relevant binding site is indeed a denuded
      glycan, and that denuded glycans are enriched in septal PG rather than
      distributed uniformly around the sacculus. Accumulation of denuded glycans in the
      septal PG of both E. coli and B. subtilis, organisms separated by 1 billion years
      of evolution, suggests that sequential removal of stem peptides followed by
      degradation of the glycan backbone is an ancient feature of PG turnover during
      bacterial cell division. Linking SPOR domain localization to the abundance of a
      structure (denuded glycans) present only transiently during biogenesis of septal
      PG provides a mechanism for coordinating the function of SPOR domain proteins
      with the progress of cell division. 

PMID- 26305950
TI  - Conserved mechanism for coordinating replication fork helicase assembly with
      phosphorylation of the helicase.
AB  - Dbf4-dependent kinase (DDK) phosphorylates minichromosome maintenance 2 (Mcm2)
      during S phase in yeast, and Sld3 recruits cell division cycle 45 (Cdc45) to
      minichromosome maintenance 2-7 (Mcm2-7). We show here DDK-phosphoryled Mcm2
      preferentially interacts with Cdc45 in vivo, and that Sld3 stimulates DDK
      phosphorylation of Mcm2 by 11-fold. We identified a mutation of the replication
      initiation factor Sld3, Sld3-m16, that is specifically defective in stimulating
      DDK phosphorylation of Mcm2. Wild-type expression levels of sld3-m16 result in
      severe growth and DNA replication defects. Cells expressing sld3-m16 exhibit no
      detectable Mcm2 phosphorylation in vivo, reduced replication protein A-ChIP
      signal at an origin, and diminished Go, Ichi, Ni, and San association with Mcm2
      7. Treslin, the human homolog of Sld3, stimulates human DDK phosphorylation of
      human Mcm2 by 15-fold. DDK phosphorylation of human Mcm2 decreases the affinity
      of Mcm5 for Mcm2, suggesting a potential mechanism for helicase ring opening.
      These data suggest a conserved mechanism for replication initiation: Sld3/Treslin
      coordinates Cdc45 recruitment to Mcm2-7 with DDK phosphorylation of Mcm2 during S
      phase. 

PMID- 26305951
TI  - Induction of USP25 by viral infection promotes innate antiviral responses by
      mediating the stabilization of TRAF3 and TRAF6.
AB  - Host pathogen-recognition receptors detect nucleic acid from invading viruses and
      initiate a series of signaling pathways that lead to the production of type I
      interferons (IFNs) and proinflammatory cytokines. Here, we found that a viral
      infection-induced deubiquitinase (DUB), ubiquitin-specific protease 25 (USP25)
      was required for host defense against RNA and DNA viruses. The activation of
      transcription factors IRF3 and NF-kappaB was impaired and the production of type
      I IFNs and proinflammatory cytokines was inhibited in Usp25-/- cells compared
      with the wild-type counterparts after RNA or DNA viruses infection. Consistently,
      USP25 deficient mice were more susceptible to H5N1 or HSV-1 infection compared
      with the wild-type mice. USP25 was associated with TRAF3 and TRAF6 after
      infection by RNA or DNA viruses and protected virus-induced proteasome-dependent
      or independent degradation of TRAF3 and TRAF6, respectively. Moreover,
      reconstitution of TRAF3 and TRAF6 into Usp25-/- MEFs restored virus-triggered
      production of type I IFNs and proinflammatory cytokines. Our findings thus reveal
      a previously uncovered positive feedback regulation of innate immune responses
      against RNA and DNA viruses by USP25.

PMID- 26305952
TI  - Lack of mitochondrial topoisomerase I (TOP1mt) impairs liver regeneration.
AB  - The liver has an exceptional replicative capacity following partial hepatectomy
      or chemical injuries. Cellular proliferation requires increased production of
      energy and essential metabolites, which critically depend on the mitochondria. To
      determine whether Top1mt, the vertebrate mitochondrial topoisomerase, is involved
      in this process, we studied liver regeneration after carbon tetrachloride (CCl4)
      administration. TOP1mt knockout (KO) mice showed a marked reduction in
      regeneration and hepatocyte proliferation. The hepatic mitochondrial DNA (mtDNA)
      failed to increase during recovery from CCl4 exposure. Reduced glutathione was
      also depleted, indicating increased reactive oxygen species (ROS). Steady-state
      levels of ATP, O2 consumption, mtDNA, and mitochondrial mass were also reduced in
      primary hepatocytes from CCl4-treated KO mice. To further test whether Top1mt
      acted by enabling mtDNA regeneration, we tested TOP1mt KO fibroblasts and human
      colon carcinoma HCT116 cells and measured mtDNA after 3-d treatment with ethidium
      bromide. Both types of TOP1mt knockout cells showed defective mtDNA regeneration
      following mtDNA depletion. Our study demonstrates that Top1mt is required for
      normal mtDNA homeostasis and for linking mtDNA expansion with hepatocyte
      proliferation. 

PMID- 26305953
TI  - Maize death acids, 9-lipoxygenase-derived cyclopente(a)nones, display activity as
      cytotoxic phytoalexins and transcriptional mediators.
AB  - Plant damage promotes the interaction of lipoxygenases (LOXs) with fatty acids
      yielding 9-hydroperoxides, 13-hydroperoxides, and complex arrays of oxylipins.
      The action of 13-LOX on linolenic acid enables production of 12-oxo-phytodienoic
      acid (12-OPDA) and its downstream products, termed "jasmonates." As signals,
      jasmonates have related yet distinct roles in the regulation of plant resistance
      against insect and pathogen attack. A similar pathway involving 9-LOX activity on
      linolenic and linoleic acid leads to the 12-OPDA positional isomer, 10-oxo-11
      phytodienoic acid (10-OPDA) and 10-oxo-11-phytoenoic acid (10-OPEA),
      respectively; however, physiological roles for 9-LOX cyclopentenones have
      remained unclear. In developing maize (Zea mays) leaves, southern leaf blight
      (Cochliobolus heterostrophus) infection results in dying necrotic tissue and the
      localized accumulation of 10-OPEA, 10-OPDA, and a series of related 14- and 12
      carbon metabolites, collectively termed "death acids." 10-OPEA accumulation
      becomes wound inducible within fungal-infected tissues and at physiologically
      relevant concentrations acts as a phytoalexin by suppressing the growth of fungi
      and herbivores including Aspergillus flavus, Fusarium verticillioides, and
      Helicoverpa zea. Unlike previously established maize phytoalexins, 10-OPEA and 10
      OPDA display significant phytotoxicity. Both 12-OPDA and 10-OPEA promote the
      transcription of defense genes encoding glutathione S transferases, cytochrome
      P450s, and pathogenesis-related proteins. In contrast, 10-OPEA only weakly
      promotes the accumulation of multiple protease inhibitor transcripts. Consistent
      with a role in dying tissue, 10-OPEA application promotes cysteine protease
      activation and cell death, which is inhibited by overexpression of the cysteine
      protease inhibitor maize cystatin-9. Unlike jasmonates, functions for 10-OPEA and
      associated death acids are consistent with specialized roles in local defense
      reactions. 

PMID- 26305954
TI  - Burkholderia bacteria infectiously induce the proto-farming symbiosis of
      Dictyostelium amoebae and food bacteria.
AB  - Symbiotic associations can allow an organism to acquire novel traits by accessing
      the genetic repertoire of its partner. In the Dictyostelium discoideum farming
      symbiosis, certain amoebas (termed "farmers") stably associate with bacterial
      partners. Farmers can suffer a reproductive cost but also gain beneficial
      capabilities, such as carriage of bacterial food (proto-farming) and defense
      against competitors. Farming status previously has been attributed to amoeba
      genotype, but the role of bacterial partners in its induction has not been
      examined. Here, we explore the role of bacterial associates in the initiation,
      maintenance, and phenotypic effects of the farming symbiosis. We demonstrate that
      two clades of farmer-associated Burkholderia isolates colonize D. discoideum
      nonfarmers and infectiously endow them with farmer-like characteristics,
      indicating that Burkholderia symbionts are a major driver of the farming
      phenomenon. Under food-rich conditions, Burkholderia-colonized amoebas produce
      fewer spores than uncolonized counterparts, with the severity of this reduction
      being dependent on the Burkholderia colonizer. However, the induction of food
      carriage by Burkholderia colonization may be considered a conditionally adaptive
      trait because it can confer an advantage to the amoeba host when grown in food
      limiting conditions. We observed Burkholderia inside and outside colonized D.
      discoideum spores after fruiting body formation; this observation, together with
      the ability of Burkholderia to colonize new amoebas, suggests a mixed mode of
      symbiont transmission. These results change our understanding of the D.
      discoideum farming symbiosis by establishing that the bacterial partner,
      Burkholderia, is an important causative agent of the farming phenomenon. 

PMID- 26305955
TI  - Contact-dependent growth inhibition toxins exploit multiple independent cell
      entry pathways.
AB  - Contact-dependent growth inhibition (CDI) systems function to deliver toxins into
      neighboring bacterial cells. CDI+ bacteria export filamentous CdiA effector
      proteins, which extend from the inhibitor-cell surface to interact with receptors
      on neighboring target bacteria. Upon binding its receptor, CdiA delivers a toxin
      derived from its C-terminal region. CdiA C-terminal (CdiA-CT) sequences are
      highly variable between bacteria, reflecting the multitude of CDI toxin
      activities. Here, we show that several CdiA-CT regions are composed of two
      domains, each with a distinct function during CDI. The C-terminal domain
      typically possesses toxic nuclease activity, whereas the N-terminal domain
      appears to control toxin transport into target bacteria. Using genetic
      approaches, we identified ptsG, metI, rbsC, gltK/gltJ, yciB, and ftsH mutations
      that confer resistance to specific CdiA-CTs. The resistance mutations all disrupt
      expression of inner-membrane proteins, suggesting that these proteins are
      exploited for toxin entry into target cells. Moreover, each mutation only
      protects against inhibition by a subset of CdiA-CTs that share similar N-terminal
      domains. We propose that, following delivery of CdiA-CTs into the periplasm, the
      N-terminal domains bind specific inner-membrane receptors for subsequent
      translocation into the cytoplasm. In accord with this model, we find that CDI
      nuclease domains are modular payloads that can be redirected through different
      import pathways when fused to heterologous N-terminal "translocation domains."
      These results highlight the plasticity of CDI toxin delivery and suggest that the
      underlying translocation mechanisms could be harnessed to deliver other
      antimicrobial agents into Gram-negative bacteria.

PMID- 26305956
TI  - Cross-strand binding of TFAM to a single mtDNA molecule forms the mitochondrial
      nucleoid.
AB  - Mammalian mitochondrial DNA (mtDNA) is packaged by mitochondrial transcription
      factor A (TFAM) into mitochondrial nucleoids that are of key importance in
      controlling the transmission and expression of mtDNA. Nucleoid ultrastructure is
      poorly defined, and therefore we used a combination of biochemistry,
      superresolution microscopy, and electron microscopy to show that mitochondrial
      nucleoids have an irregular ellipsoidal shape and typically contain a single copy
      of mtDNA. Rotary shadowing electron microscopy revealed that nucleoid formation
      in vitro is a multistep process initiated by TFAM aggregation and cross-strand
      binding. Superresolution microscopy of cultivated cells showed that increased
      mtDNA copy number increases nucleoid numbers without altering their sizes.
      Electron cryo-tomography visualized nucleoids at high resolution in isolated
      mammalian mitochondria and confirmed the sizes observed by superresolution
      microscopy of cell lines. We conclude that the fundamental organizational unit of
      the mitochondrial nucleoid is a single copy of mtDNA compacted by TFAM, and we
      suggest a packaging mechanism. 

PMID- 26305957
TI  - Structure of an intermediate conformer of the spindle checkpoint protein Mad2.
AB  - The spindle checkpoint senses unattached kinetochores during prometaphase and
      inhibits the anaphase-promoting complex or cyclosome (APC/C), thus ensuring
      accurate chromosome segregation. The checkpoint protein mitotic arrest deficient
      2 (Mad2) is an unusual protein with multiple folded states. Mad2 adopts the
      closed conformation (C-Mad2) in a Mad1-Mad2 core complex. In mitosis, kinetochore
      bound Mad1-C-Mad2 recruits latent, open Mad2 (O-Mad2) from the cytosol and
      converts it to an intermediate conformer (I-Mad2), which can then bind and
      inhibit the APC/C activator cell division cycle 20 (Cdc20) as C-Mad2. Here, we
      report the crystal structure and NMR analysis of I-Mad2 bound to C-Mad2. Although
      I-Mad2 retains the O-Mad2 fold in crystal and in solution, its core structural
      elements undergo discernible rigid-body movements and more closely resemble C
      Mad2. Residues exhibiting methyl chemical shift changes in I-Mad2 form a
      contiguous, interior network that connects its C-Mad2-binding site to the
      conformationally malleable C-terminal region. Mutations of residues at the I-Mad2
      C-Mad2 interface hinder I-Mad2 formation and impede the structural transition of
      Mad2. Our study provides insight into the conformational activation of Mad2 and
      establishes the basis of allosteric communication between two distal sites in
      Mad2. 

PMID- 26305959
TI  - P hacking in biology: An open secret.

PMID- 26305958
TI  - Transcription factor p63 controls the reserve status but not the stemness of
      horizontal basal cells in the olfactory epithelium.
AB  - Adult tissue stem cells can serve two broad functions: to participate actively in
      the maintenance and regeneration of a tissue or to wait in reserve and
      participate only when activated from a dormant state. The adult olfactory
      epithelium, a site for ongoing, life-long, robust neurogenesis, contains both of
      these functional stem cell types. Globose basal cells (GBCs) act as the active
      stem cell population and can give rise to all the differentiated cells found in
      the normal tissue. Horizontal basal cells (HBCs) act as reserve stem cells and
      remain dormant unless activated by tissue injury. Here we show that HBC
      activation following injury by the olfactotoxic gas methyl bromide is coincident
      with the down-regulation of protein 63 (p63) but anticipates HBC proliferation.
      Gain- and loss-of-function studies show that this down-regulation of p63 is
      necessary and sufficient for HBC activation. Moreover, activated HBCs give rise
      to GBCs that persist for months and continue to act as bona fide stem cells by
      participating in tissue maintenance and regeneration over the long term. Our
      analysis provides mechanistic insight into the dynamics between tissue stem cell
      subtypes and demonstrates that p63 regulates the reserve state but not the stem
      cell status of HBCs. 

PMID- 26305960
TI  - Reply to Veresoglou: Overdependence on "significance" testing in biology.

PMID- 26305962
TI  - Shifting patterns in Pacific climate, West Coast salmon survival rates, and
      increased volatility in ecosystem services.

PMID- 26305961
TI  - NLRP3 deficiency protects from type 1 diabetes through the regulation of
      chemotaxis into the pancreatic islets.
AB  - Studies in animal models and human subjects have shown that both innate and
      adaptive immunity contribute to the pathogenesis of type 1 diabetes (T1D).
      Whereas the role of TLR signaling pathways in T1D has been extensively studied,
      the contribution of the nucleotide-binding oligomerization domain, leucine-rich
      repeat and pyrin domain-containing protein (NLRP) 3 inflammasome pathway remains
      to be explored. In this study, we report that NLRP3 plays an important role in
      the development of T1D in the nonobese diabetic (NOD) mouse model. NLRP3
      deficiency not only affected T-cell activation and Th1 differentiation, but also
      modulated pathogenic T-cell migration to the pancreatic islet. The presence of
      NLRP3 is critical for the expression of the chemokine receptors CCR5 and CXCR3 on
      T cells. More importantly, NLRP3 ablation reduced the expression of chemokine
      genes CCL5 and CXCL10 on pancreatic islet cells in an IRF-1-dependent manner. Our
      results suggest that molecules involved in chemotaxis, accompanied by the
      activation of the NLRP3 inflammasome, may be effective targets for the treatment
      of T1D. 

PMID- 26305963
TI  - Antibiotics and the art of bacterial war.

PMID- 26305964
TI  - Positive feedback between RNA-binding protein HuD and transcription factor SATB1
      promotes neurogenesis.
AB  - The mammalian embryonic lethal abnormal vision (ELAV)-like protein HuD is a
      neuronal RNA-binding protein implicated in neuronal development, plasticity, and
      diseases. Although HuD has long been associated with neuronal development, the
      functions of HuD in neural stem cell differentiation and the underlying
      mechanisms have gone largely unexplored. Here we show that HuD promotes neuronal
      differentiation of neural stem/progenitor cells (NSCs) in the adult
      subventricular zone by stabilizing the mRNA of special adenine-thymine (AT)-rich
      DNA-binding protein 1 (SATB1), a critical transcriptional regulator in
      neurodevelopment. We find that SATB1 deficiency impairs the neuronal
      differentiation of NSCs, whereas SATB1 overexpression rescues the neuronal
      differentiation phenotypes resulting from HuD deficiency. Interestingly, we also
      discover that SATB1 is a transcriptional activator of HuD during NSC neuronal
      differentiation. In addition, we demonstrate that NeuroD1, a neuronal master
      regulator, is a direct downstream target of SATB1. Therefore, HuD and SATB1 form
      a positive regulatory loop that enhances NeuroD1 transcription and subsequent
      neuronal differentiation. Our results here reveal a novel positive feedback
      network between an RNA-binding protein and a transcription factor that plays
      critical regulatory roles in neurogenesis. 

PMID- 26305965
TI  - Isotope-specific and amino acid-specific heavy atom substitutions alter barrier
      crossing in human purine nucleoside phosphorylase.
AB  - Computational chemistry predicts that atomic motions on the femtosecond timescale
      are coupled to transition-state formation (barrier-crossing) in human purine
      nucleoside phosphorylase (PNP). The prediction is experimentally supported by
      slowed catalytic site chemistry in isotopically labeled PNP (13C, 15N, and 2H).
      However, other explanations are possible, including altered volume or bond
      polarization from carbon-deuterium bonds or propagation of the femtosecond bond
      motions into slower (nanoseconds to milliseconds) motions of the larger protein
      architecture to alter catalytic site chemistry. We address these possibilities by
      analysis of chemistry rates in isotope-specific labeled PNPs. Catalytic site
      chemistry was slowed for both [2H]PNP and [13C, 15N]PNP in proportion to their
      altered protein masses. Secondary effects emanating from carbon-deuterium bond
      properties can therefore be eliminated. Heavy-enzyme mass effects were probed for
      local or global contributions to catalytic site chemistry by generating [15N,
      2H]His8-PNP. Of the eight His per subunit, three participate in contacts to the
      bound reactants and five are remote from the catalytic sites. [15N, 2H]His8-PNP
      had reduced catalytic site chemistry larger than proportional to the enzymatic
      mass difference. Altered barrier crossing when only His are heavy supports local
      catalytic site femtosecond perturbations coupled to transition-state formation.
      Isotope-specific and amino acid specific labels extend the use of heavy enzyme
      methods to distinguish global from local isotope effects.

PMID- 26305966
TI  - Deep two-photon brain imaging with a red-shifted fluorometric Ca2+ indicator.
AB  - In vivo Ca2+ imaging of neuronal populations in deep cortical layers has remained
      a major challenge, as the recording depth of two-photon microscopy is limited
      because of the scattering and absorption of photons in brain tissue. A possible
      strategy to increase the imaging depth is the use of red-shifted fluorescent
      dyes, as scattering of photons is reduced at long wavelengths. Here, we tested
      the red-shifted fluorescent Ca2+ indicator Cal-590 for deep tissue experiments in
      the mouse cortex in vivo. In experiments involving bulk loading of neurons with
      the acetoxymethyl (AM) ester version of Cal-590, combined two-photon imaging and
      cell-attached recordings revealed that, despite the relatively low affinity of
      Cal-590 for Ca2+ (Kd=561 nM), single-action potential-evoked Ca2+ transients were
      discernable in most neurons with a good signal-to-noise ratio. Action potential
      dependent Ca2+ transients were recorded in neurons of all six layers of the
      cortex at depths of up to -900 um below the pial surface. We demonstrate that Cal
      590 is also suited for multicolor functional imaging experiments in combination
      with other Ca2+ indicators. Ca2+ transients in the dendrites of an individual
      Oregon green 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-1 (OGB-1)
      labeled neuron and the surrounding population of Cal-590-labeled cells were
      recorded simultaneously on two spectrally separated detection channels. We
      conclude that the red-shifted Ca2+ indicator Cal-590 is well suited for in vivo
      two-photon Ca2+ imaging experiments in all layers of mouse cortex. In combination
      with spectrally different Ca2+ indicators, such as OGB-1, Cal-590 can be readily
      used for simultaneous multicolor functional imaging experiments.

PMID- 26305967
TI  - Evasion of affinity-based selection in germinal centers by Epstein-Barr virus
      LMP2A.
AB  - Epstein-Barr virus (EBV) infects germinal center (GC) B cells and establishes
      persistent infection in memory B cells. EBV-infected B cells can cause B-cell
      malignancies in humans with T- or natural killer-cell deficiency. We now find
      that EBV-encoded latent membrane protein 2A (LMP2A) mimics B-cell antigen
      receptor (BCR) signaling in murine GC B cells, causing altered humoral immune
      responses and autoimmune diseases. Investigation of the impact of LMP2A on B-cell
      differentiation in mice that conditionally express LMP2A in GC B cells or all B
      lineage cells found LMP2A expression enhanced not only BCR signals but also
      plasma cell differentiation in vitro and in vivo. Conditional LMP2A expression in
      GC B cells resulted in preferential selection of low-affinity antibody-producing
      B cells despite apparently normal GC formation. GC B-cell-specific LMP2A
      expression led to systemic lupus erythematosus-like autoimmune phenotypes in an
      age-dependent manner. Epigenetic profiling of LMP2A B cells found increased
      H3K27ac and H3K4me1 signals at the zinc finger and bric-a-brac, tramtrack domain
      containing protein 20 locus. We conclude that LMP2A reduces the stringency of GC
      B-cell selection and may contribute to persistent EBV infection and pathogenesis
      by providing GC B cells with excessive prosurvival effects. 

PMID- 26305968
TI  - Synapse-specific IL-1 receptor subunit reconfiguration augments vulnerability to
      IL-1beta in the aged hippocampus.
AB  - In the aged brain, synaptic plasticity and memory show increased vulnerability to
      impairment by the inflammatory cytokine interleukin 1beta (IL-1beta). In this
      study, we evaluated the possibility that synapses may directly undergo
      maladaptive changes with age that augment sensitivity to IL-1beta impairment. In
      hippocampal neuronal cultures, IL-1beta increased the expression of the IL-1
      receptor type 1 and the accessory coreceptor AcP (proinflammatory), but not of
      the AcPb (prosurvival) subunit, a reconfiguration that potentiates the
      responsiveness of neurons to IL-1beta. To evaluate whether synapses develop a
      similar heightened sensitivity to IL-1beta with age, we used an assay to track
      long-term potentiation (LTP) in synaptosomes. We found that IL-1beta impairs LTP
      directly at the synapse and that sensitivity to IL-1beta is augmented in aged
      hippocampal synapses. The increased synaptic sensitivity to IL-1beta was due to
      IL-1 receptor subunit reconfiguration, characterized by a shift in the AcP/AcPb
      ratio, paralleling our culture data. We suggest that the age-related increase in
      brain IL-1beta levels drives a shift in IL-1 receptor configuration, thus
      heightening the sensitivity to IL-1beta. Accordingly, selective blocking of AcP
      dependent signaling with Toll-IL-1 receptor domain peptidomimetics prevented IL
      1beta-mediated LTP suppression and blocked the memory impairment induced in aged
      mice by peripheral immune challenge (bacterial lipopolysaccharide). Overall, this
      study demonstrates that increased AcP signaling, specifically at the synapse,
      underlies the augmented vulnerability to cognitive impairment by IL-1beta that
      occurs with age. 

PMID- 26305970
TI  - Profile of Jay C. Dunlap.

PMID- 26305969
TI  - Uterine activin receptor-like kinase 5 is crucial for blastocyst implantation and
      placental development.
AB  - Members of the transforming growth factor beta (TGF-beta) superfamily are key
      regulators in most developmental and physiological processes. However, the in
      vivo roles of TGF-beta signaling in female reproduction remain uncertain. Activin
      receptor-like kinase 5 (ALK5) is the major type 1 receptor for the TGF-beta
      subfamily. Absence of ALK5 leads to early embryonic lethality because of severe
      defects in vascular development. In this study, we conditionally ablated uterine
      ALK5 using progesterone receptor-cre mice to define the physiological roles of
      ALK5 in female reproduction. Despite normal ovarian functions and artificial
      decidualization in conditional knockout (cKO) mice, absence of uterine ALK5
      resulted in substantially reduced female reproduction due to abnormalities
      observed at different stages of pregnancy, including implantation defects,
      disorganization of trophoblast cells, fewer uterine natural killer (uNK) cells,
      and impairment of spiral artery remodeling. In our microarray analysis, genes
      encoding proteins involved in cytokine-cytokine receptor interactions and NK cell
      mediated cytotoxicity were down-regulated in cKO decidua compared with control
      decidua. Flow cytometry confirmed a 10-fold decrease in uNK cells in cKO versus
      control decidua. According to these data, we hypothesize that TGF-beta acts on
      decidual cells via ALK5 to induce expression of other growth factors and
      cytokines, which are key regulators in luminal epithelium proliferation,
      trophoblast development, and uNK maturation during pregnancy. Our findings not
      only generate a mouse model to study TGF-beta signaling in female reproduction
      but also shed light on the pathogenesis of many pregnancy complications in human,
      such as recurrent spontaneous abortion, preeclampsia, and intrauterine growth
      restriction. 

PMID- 26305971
TI  - Profile of Xinnian Dong.

PMID- 26305972
TI  - Role of PKA signaling in D2 receptor-expressing neurons in the core of the
      nucleus accumbens in aversive learning.
AB  - The nucleus accumbens (NAc) serves as a key neural substrate for aversive
      learning and consists of two distinct subpopulations of medium-sized spiny
      neurons (MSNs). The MSNs of the direct pathway (dMSNs) and the indirect pathway
      (iMSNs) predominantly express dopamine (DA) D1 and D2 receptors, respectively,
      and are positively and negatively modulated by DA transmitters via Gs- and Gi
      coupled cAMP-dependent protein kinase A (PKA) signaling cascades, respectively.
      In this investigation, we addressed how intracellular PKA signaling is involved
      in aversive learning in a cell type-specific manner. When the transmission of
      either dMSNs or iMSNs was unilaterally blocked by pathway-specific expression of
      transmission-blocking tetanus toxin, infusion of PKA inhibitors into the intact
      side of the NAc core abolished passive avoidance learning toward an electric
      shock in the indirect pathway-blocked mice, but not in the direct pathway-blocked
      mice. We then examined temporal changes in PKA activity in dMSNs and iMSNs in
      behaving mice by monitoring Forster resonance energy transfer responses of the
      PKA biosensor with the aid of microendoscopy. PKA activity was increased in iMSNs
      and decreased in dMSNs in both aversive memory formation and retrieval.
      Importantly, the increased PKA activity in iMSNs disappeared when aversive memory
      was prevented by keeping mice in the conditioning apparatus. Furthermore, the
      increase in PKA activity in iMSNs by aversive stimuli reflected facilitation of
      aversive memory retention. These results indicate that PKA signaling in iMSNs
      plays a critical role in both aversive memory formation and retention. 

PMID- 26305973
TI  - Effect of aging on muscle mitochondrial substrate utilization in humans.
AB  - Previous studies have implicated age-associated reductions in mitochondrial
      oxidative phosphorylation activity in skeletal muscle as a predisposing factor
      for intramyocellular lipid (IMCL) accumulation and muscle insulin resistance (IR)
      in the elderly. To further investigate potential alterations in muscle
      mitochondrial function associated with aging, we assessed basal and insulin
      stimulated rates of muscle pyruvate dehydrogenase (VPDH) flux relative to citrate
      synthase flux (VCS) in healthy lean, elderly subjects and healthy young body mass
      index- and activity-matched subjects. VPDH/VCS flux was assessed from the (13)C
      incorporation from of infused [1-13C] glucose into glutamate [4-13C] relative to
      alanine [3-13C] assessed by LC-tandem MS in muscle biopsies. Insulin-stimulated
      rates of muscle glucose uptake were reduced by 25% (P<0.01) in the elderly
      subjects and were associated with ~70% (P<0.04) increase in IMCL, assessed by 1H
      magnetic resonance spectroscopy. Basal VPDH/VCS fluxes were similar between the
      groups (young: 0.20+/-0.03; elderly: 0.14+/-0.03) and increased approximately
      threefold in the young subjects following insulin stimulation. However, this
      increase was severely blunted in the elderly subjects (young: 0.55+/-0.04;
      elderly: 0.18+/-0.02, P=0.0002) and was associated with an ~40% (P=0.004)
      reduction in insulin activation of Akt. These results provide new insights into
      acquired mitochondrial abnormalities associated with aging and demonstrate that
      age-associated reductions in muscle mitochondrial function and increased IMCL are
      associated with a marked inability of mitochondria to switch from lipid to
      glucose oxidation during insulin stimulation.

PMID- 26305974
TI  - Recognition and sequestration of omega-fatty acids by a cavitand receptor.
AB  - One of the largest driving forces for molecular association in aqueous solution
      is the hydrophobic effect, and many synthetic receptors with hydrophobic
      interiors have been devised for molecular recognition studies in water. Attempts
      to create the longer, narrower cavities appropriate for long-chain fatty acids
      have been thwarted by solvophobic collapse of the synthetic receptors, giving
      structures that have no internal spaces. The collapse generally involves the
      stacking of aromatic panels onto themselves. We describe here the synthesis and
      application of a deep cavitand receptor featuring "prestacked" aromatic panels at
      the upper rim of the binding pocket. The cavitand remains open and readily
      sequesters biologically relevant long-chain molecules-unsaturated omega-3, -6,
      and -9 fatty acids and derivatives such as anandamide-from aqueous media. The
      cavitand exists in isomeric forms with different stacking geometries and n
      alkanes were used to characterize the binding modes and conformational
      properties. Long alkyl chains are accommodated in inverted J-shaped
      conformations. An analogous cavitand with electron-rich aromatic walls was
      prepared and comparative binding experiments indicated the role of intramolecular
      stacking in the binding properties of these deep container molecules. 

PMID- 26305976
TI  - Dynamic equilibrium between closed and partially closed states of the bacterial
      Enzyme I unveiled by solution NMR and X-ray scattering.
AB  - Enzyme I (EI) is the first component in the bacterial phosphotransferase system,
      a signal transduction pathway in which phosphoryl transfer through a series of
      bimolecular protein-protein interactions is coupled to sugar transport across the
      membrane. EI is a multidomain, 128-kDa homodimer that has been shown to exist in
      two conformational states related to one another by two large (50-90 degrees )
      rigid body domain reorientations. The open conformation of apo EI allows
      phosphoryl transfer from His189 located in the N-terminal domain alpha/beta
      (EIN(alpha/beta)) subdomain to the downstream protein partner bound to the
      EIN(alpha) subdomain. The closed conformation, observed in a trapped phosphoryl
      transfer intermediate, brings the EIN(alpha/beta) subdomain into close proximity
      to the C-terminal dimerization domain (EIC), thereby permitting in-line
      phosphoryl transfer from phosphoenolpyruvate (PEP) bound to EIC to His189. Here,
      we investigate the solution conformation of a complex of an active site mutant of
      EI (H189A) with PEP. Simulated annealing refinement driven simultaneously by
      solution small angle X-ray scattering and NMR residual dipolar coupling data
      demonstrates unambiguously that the EI(H189A)-PEP complex exists in a dynamic
      equilibrium between two approximately equally populated conformational states,
      one corresponding to the closed structure and the other to a partially closed
      species. The latter likely represents an intermediate in the open-to-closed
      transition. 

PMID- 26305975
TI  - Local host specialization, host-switching, and dispersal shape the regional
      distributions of avian haemosporidian parasites.
AB  - The drivers of regional parasite distributions are poorly understood, especially
      in comparison with those of free-living species. For vector-transmitted
      parasites, in particular, distributions might be influenced by host-switching and
      by parasite dispersal with primary hosts and vectors. We surveyed haemosporidian
      blood parasites (Plasmodium and Haemoproteus) of small land birds in eastern
      North America to characterize a regional parasite community. Distributions of
      parasite populations generally reflected distributions of their hosts across the
      region. However, when the interdependence between hosts and parasites was
      controlled statistically, local host assemblages were related to regional
      climatic gradients, but parasite assemblages were not. Moreover, because parasite
      assemblage similarity does not decrease with distance when controlling for host
      assemblages and climate, parasites evidently disperse readily within the
      distributions of their hosts. The degree of specialization on hosts varied in
      some parasite lineages over short periods and small geographic distances
      independently of the diversity of available hosts and potentially competing
      parasite lineages. Nonrandom spatial turnover was apparent in parasite lineages
      infecting one host species that was well-sampled within a single year across its
      range, plausibly reflecting localized adaptations of hosts and parasites.
      Overall, populations of avian hosts generally determine the geographic
      distributions of haemosporidian parasites. However, parasites are not dispersal
      limited within their host distributions, and they may switch hosts readily. 

PMID- 26305977
TI  - Role of activating transcription factor 3 in the synthesis of latency-associated
      transcript and maintenance of herpes simplex virus 1 in latent state in ganglia.
AB  - A key property of herpes simplex viruses (HSVs) is their ability to establish
      latent infection in sensory or autonomic ganglia and to reactivate on physical,
      hormonal, or emotional stress. In latently infected ganglia, HSVs express a long
      noncoding RNA, a latency-associated transcript (LAT), which plays a key role in
      maintaining latently infected neurons, but not viral proteins. To investigate the
      events leading to reactivation, we examined the use of ganglionic organ cultures
      that enable rapid reactivation in medium containing antibody to nerve growth
      factor (NGF) or delayed reactivation in medium containing NGF and epidermal
      growth factor (EGF). Here we report the discovery that activating transcription
      factor 3 (ATF3), a stress response protein, profoundly affects the interaction of
      HSV with its host. Specifically, (i) ATF3 is induced by stress, such as
      inhibition of protein synthesis or infection; (ii) in infected cells, ATF3
      enhances the accumulation of LAT by acting on the response elements in the
      promoter of the LAT precursor RNA; (iii) ATF3 is induced nearly 100-fold in
      ganglionic organ cultures; and (iv) ATF3 plays a key role in the maintenance of
      the latent state, inasmuch as expression of ATF3 bereft of the C-terminal
      activation domain acts as a dominant negative factor, inducing HSV gene
      expression in ganglionic organ cultures harboring latent virus and incubated in
      medium containing NGF and EGF. Thus, ATF3 is a component of a cluster of cellular
      proteins that together with LAT maintain the integrity of the neurons harboring
      latent virus. 

PMID- 26305979
TI  - Retraction for Maitra et al., Mutant surfactant A2 proteins associated with
      familial pulmonary fibrosis and lung cancer induce TGF-beta1 secretion.

PMID- 26305980
TI  - Relationship between Segmental Relaxation of Polystyrene Films and Stick-Slip
      Behavior during Dynamic Wetting of Liquid Droplets on Their Surfaces.
AB  - A novel method was previously reported for detecting the glass transition of thin
      polystyrene (PS) films by correlating the relationships between the temperature
      dependent viscoelasticity of the PS films and stick-slip behavior on their
      surfaces during dynamic wetting of liquid droplets. In the present study, the
      frequency dependence of the stick-slip behavior is investigated. The results show
      that the stick-slip behavior of liquid dynamic wetting on PS films is dependent
      on the contact line velocity, which is related to the deformation frequency of
      the PS surface during the moving liquid front. The stick-slip behavior was
      revealed to be determined by a dimensionless parameter (xi), which is the ratio
      of the PS segmental relaxation time (taualpha) and the characteristic time (tauc)
      for PS surface deformation near the droplet contact line. When xi is close to 1
      (taualpha ~ tauc), the Deltatheta (jumping angle), a scale of the stick-slip
      behavior, reaches a maximum. This correlation between Deltatheta and xi
      demonstrates that the stick-slip behavior is related to the energy dissipation
      caused by the PS alpha-relaxation process, and the peak temperature (or
      frequency) in Deltatheta corresponds to the alpha-relaxation temperature (time)
      of the polymer. These results strongly demonstrate that the utilization of the
      stick-slip behavior is a creditable method, similar to dynamic viscoelastic
      measurement, for probing the glass transition and segmental relaxation of thin
      polymer films. 

PMID- 26305978
TI  - Hepatic ANGPTL3 regulates adipose tissue energy homeostasis.
AB  - Angiopoietin-like protein 3 (ANGPTL3) is a circulating inhibitor of lipoprotein
      and endothelial lipase whose physiological function has remained obscure. Here we
      show that ANGPTL3 plays a major role in promoting uptake of circulating very low
      density lipoprotein-triglycerides (VLDL-TGs) into white adipose tissue (WAT)
      rather than oxidative tissues (skeletal muscle, heart brown adipose tissue) in
      the fed state. This conclusion emerged from studies of Angptl3(-/-) mice. Whereas
      feeding increased VLDL-TG uptake into WAT eightfold in wild-type mice, no
      increase occurred in fed Angptl3(-/-) animals. Despite the reduction in delivery
      to and retention of TG in WAT, fat mass was largely preserved by a compensatory
      increase in de novo lipogenesis in Angptl3(-/-) mice. Glucose uptake into WAT was
      increased 10-fold in KO mice, and tracer studies revealed increased conversion of
      glucose to fatty acids in WAT but not liver. It is likely that the increased
      uptake of glucose into WAT explains the increased insulin sensitivity associated
      with inactivation of ANGPTL3. The beneficial effects of ANGPTL3 deficiency on
      both glucose and lipoprotein metabolism make it an attractive therapeutic target.

PMID- 26305981
TI  - Cytokine treatment in cancer immunotherapy.

PMID- 26305982
TI  - Fibronectin orchestrates thrombosis and hemostasis.

PMID- 26305983
TI  - FBH1: a new checkpoint factor.

PMID- 26305984
TI  - SRSF1 inhibition of HIV-1 gene expression.

PMID- 26305985
TI  - Impact of influenza PA-X on host response.

PMID- 26305986
TI  - The MYC/miR-17-92 axis in lymphoproliferative disorders: A common pathway with
      therapeutic potential.
AB  - MicroRNAs (miRNAs) represent a class of small non-coding single-stranded RNA
      molecules acting as master regulators of gene expression post transcriptionally
      by inhibiting the translation or inducing the degradation of target messenger
      RNAs (mRNAs). In particular, the miR-17-92 cluster is widely expressed in many
      different cell types and is essential for many developmental and pathogenic
      processes. As a strong oncogene, miR-17-92 can regulate multiple cellular
      processes that favor malignant transformation, promoting cell survival, rapid
      cell proliferation, and increased angiogenesis. The miR-17-92 cluster has been
      reported to be involved in hematopoietic malignancies including diffuse large B
      cell lymphoma, mantle cell lymphoma, Burkitt's lymphoma, and chronic lymphocytic
      leukemia. Given the multiple and potent effects on cellular proliferation and
      apoptosis exerted by the miR-17-92 cluster, miRNAs belonging to the cluster
      surely represent attractive targets for cancer therapy also in the context of
      lymphoproliferative disorders. In the present review, we focus on the role of the
      miR-17-92 cluster in lymphoproliferative disorders, including
      diagnostic/prognostic implications, and on the potential applications of anti
      miRNAs based therapies targeting miRNAs belonging to the cluster. 

PMID- 26305988
TI  - Dissecting Xuesaitong's mechanisms on preventing stroke based on the microarray
      and connectivity map.
AB  - Elucidating action mechanisms of Chinese medicines has remained a challenging
      task due to the chemical and biological complexity that needs to be resolved. In
      this study we applied a gene expression data and connectivity map (CMAP) based
      approach to study action mechanisms of a Chinese medicine Xuesaitong injection
      (XST) on preventing cerebral ischemia-reperfusion injury. XST is a standardized
      patent Chinese medicine of Panax notoginseng roots and it has long been used for
      the effective prevention and treatment of stroke in China. However, more research
      is needed to understand the mechanisms underlying its effects against ischemic
      stroke. We first evaluated the effect of XST against ischemic stroke in an
      ischemia-reperfusion rat animal model and dissected its mechanisms based on gene
      expression data of injured brain. The results showed that treatment with XST
      significantly attenuated infarct area and histological damage. Based upon pathway
      analysis and the CMAP query of microarray data, anti-inflammatory response and
      anti-platelet coagulation were found as the major mechanisms of XST against
      stroke, which were further validated in vitro and with pharmacological assays of
      serum. We demonstrated the feasibility of applying the combination of the
      microarray with the CMAP in identifying mechanisms of Chinese medicine. 

PMID- 26305987
TI  - Influence of non-steroidal anti-inflammatory drugs on Drosophila melanogaster
      longevity.
AB  - Most age-related diseases and aging itself are associated with chronic
      inflammation. Thus pharmacological inhibition of inflammatory processes may be
      effective antiaging strategy. In this study we demonstrated that treatment of
      Drosophila melanogaster with 10 non-steroidal anti-inflammatory drugs (NSAIDs:
      CAY10404, aspirin, APHS, SC-560, NS-398, SC-58125, valeroyl salicylate, trans
      resveratrol, valdecoxib, licofelone) leads to extension of lifespan, delays age
      dependent decline of locomotor activity and increases stress resistance. The
      effect of the lifespan increase was associated with decrease of fecundity.
      Depending on the concentration, NSAIDs demonstrated both anti- and pro-oxidant
      properties in Drosophila tissues. However, we failed to identify clear
      correlation between antioxidant properties of NSAIDs and their pro-longevity
      effects. The lifespan extending effects of APHS, SC-58125, valeroyl salicylate,
      trans-resveratrol, valdecoxib, and licofelone were more pronounced in males,
      valdecoxib and aspirin - in females. We demonstrated that lifespan extension
      effect of NSAIDs was abolished in flies with defective genes involved in Pkh2
      ypk1-lem3-tat2 pathway. 

PMID- 26305989
TI  - Fibromyalgia criteria in a tertiary pain clinic.

PMID- 26305991
TI  - Activated Ester Containing Polymers: Opportunities and Challenges for the Design
      of Functional Macromolecules.

PMID- 26305990
TI  - A listening skill educational intervention for pediatric rehabilitation
      clinicians: A mixed-methods pilot study.
AB  - OBJECTIVE: To prepare for an RCT by examining the effects of an educational
      intervention on the listening skills of pediatric rehabilitation clinicians,
      piloting study procedures, and investigating participants' learning experiences.
      METHODS: Six experienced clinicians received the intervention, consisting of
      video simulations and solution-focused coaching regarding personal listening
      goals. Self- and observer-rated measures of listening skill were completed and
      qualitative information was gathered in interviews and a member checking session.
      RESULTS: Significant change on self-reported listening skills was found from pre-
      to post-test and/or follow-up. The pilot provided useful information to improve
      the study protocol, including the addition of an initial orientation to listening
      skills. Participants found the intervention to be a highly valuable and intense
      learning experience, and reported immediate changes to their clinical and
      interprofessional practice. CONCLUSION: The educational intervention has the
      potential to be an effective means to enhance the listening skills of practicing
      pediatric rehabilitation clinicians.

PMID- 26305992
TI  - An Advanced Practice Nurse Coordinated Multidisciplinary Intervention for
      Patients with Late-Stage Cancer: A Cluster Randomized Trial.
AB  - BACKGROUND: Early palliative care provided through a palliative care consultative
      service is effective in enhancing patient outcomes. However, it is unknown
      whether the integration of palliative care as part of routine comprehensive
      cancer care improves patients' self-reported clinical outcomes. OBJECTIVE: The
      objective of this study was to evaluate the effects of a multidisciplinary
      coordinated intervention by advanced practice nurses at the clinic level on
      outcomes with patients newly diagnosed with late-stage cancer. METHODS: A
      clustered, randomized, controlled trial design was used. Four disease-specific
      multidisciplinary clinics were randomized to the 10-week intervention
      (gynecologic and lung clinics) or to enhanced usual care (head and neck and
      gastrointestinal clinics). Patient primary outcomes (symptoms, health distress,
      depression, functional status, self-reported health) were collected at baseline
      and one and three months, and secondary outcomes were collected one and three
      months postbaseline. General linear mixed model analyses with a covariance
      structure of within-subject correlation was used to examine the intervention's
      effect. RESULTS: The sample included 146 patients with newly diagnosed late-stage
      cancers. We found no differences between the two groups on the primary patient
      reported outcomes at one and three months postbaseline; however, physical and
      emotional symptoms remained stable or significantly improved from baseline for
      both groups. Overall, secondary outcomes remained stable within the groups.
      CONCLUSION: In this translational study, we demonstrated that if patients newly
      diagnosed with late-stage cancer were managed by disease-specific
      multidisciplinary teams who palliated their symptoms, providing whole-patient
      care, patient outcomes remained stable or improved.

PMID- 26305994
TI  - Nanonickel-catalyzed Suzuki-Miyaura cross-couplings in water.
AB  - Nickel nanoparticles, formed in situ and used in combination with micellar
      catalysis, catalyze Suzuki-Miyaura cross-couplings in water under very mild
      reaction conditions. 

PMID- 26305993
TI  - A potent neutralizing IgM mAb targeting the N218 epitope on E2 protein protects
      against Chikungunya virus pathogenesis.
AB  - Chikungunya virus (CHIKV) is a medically important human viral pathogen that
      causes Chikungunya fever accompanied with debilitating and persistent joint pain.
      Host-elicited or passively-transferred monoclonal antibodies (mAb) are essential
      mediators of CHIKV clearance. Therefore, this study aimed to generate and
      characterize a panel of mAbs for their neutralization efficacy against CHIKV
      infection in a cell-based and murine model. To evaluate their antigenicity and
      neutralization profile, indirect enzyme-linked immunosorbent assay (ELISA), an
      immunofluorescence assay (IFA) and a plaque reduction neutralization test were
      performed on mAbs of IgM isotype. CHIKV escape mutants against mAb 3E7b
      neutralization were generated, and reverse genetics techniques were then used to
      create an infectious CHIKV clone with a single mutation. 3E7b was also
      administered to neonate mice prior or after CHIKV infection. The survival rate,
      CHIKV burden in tissues and histopathology of the limb muscles were evaluated.
      Both IgM 3E7b and 8A2c bind strongly to native CHIKV surface and potently
      neutralize CHIKV replication. Further analyses of 3E7b binding and neutralization
      of CHIKV single-mutant clones revealed that N218 of CHIKV E2 protein is a potent
      neutralizing epitope. In a pre-binding neutralization assay, 3E7b blocks CHIKV
      attachment to permissive cells, possibly by binding to the surface-accessible E2
      N218 residue. Prophylactic administration of 3E7b to neonate mice markedly
      reduced viremia and protected against CHIKV pathogenesis in various mice tissues.
      Given therapeutically at 4 h post-infection, 3E7b conferred 100% survival rate
      and similarly reduced CHIKV load in most mice tissues except the limb muscles.
      Collectively, these findings highlight the usefulness of 3E7b for future
      prophylactic or epitope-based vaccine design.

PMID- 26305995
TI  - An Isolated Complex of Ethyne and Gold Iodide Characterized by Broadband
      Rotational Spectroscopy and Ab initio Calculations.
AB  - A molecular complex of C2H2 and AuI has been generated and isolated in the gas
      phase through laser ablation of a gold surface in the presence of an expanding
      sample containing small percentages of C2H2 and CF3I in a buffer gas of argon.
      Rotational, B0, centrifugal distortion, DeltaJ and DeltaJK, and nuclear
      quadrupole coupling constants, chiaa(Au), chibb(Au) - chicc(Au), chiaa(I), and
      chibb(I) - chicc(I), are measured for three isotopologues of C2H2...AuI through
      broadband rotational spectroscopy. The complex is C2v and T-shaped with C2H2
      coordinating to the gold atom via donation of electrons from the pi-orbitals of
      ethyne. On formation of the complex, the C=C bond of ethyne extends by 0.032(4) A
      relative to r(C=C) in isolated ethyne when the respective r0 geometries are
      compared. The geometry of ethyne distorts such that ?(*-C-H) (where * indicates
      the midpoint of the C=C bond) is 194.7(12) degrees  in the r0 geometry of
      C2H2...AuI. Ab initio calculations at the CCSD(T)(F12*)/AVTZ level are consistent
      with the experimentally determined geometry and further allow calculation of the
      dissociation energy (De) as 136 kJ mol(-1). The chiaa(Au) and chiaa(I) nuclear
      quadrupole coupling constants of AuI and also the Au-I bond length change
      significantly on formation of the complex consistent with the strong interaction
      calculated to occur between C2H2 and AuI. 

PMID- 26305996
TI  - Evaluation of pT0 prostate cancer in patients undergoing radical prostatectomy.
AB  - OBJECTIVE: To evaluate the incidence, predictors and oncological outcomes of pT0
      prostate cancer (PCa). METHODS: We conducted a retrospective analysis of 20 222
      patients undergoing radical prostatectomy (RP) for PCa at the Mayo Clinic between
      1987 and 2012. Disease recurrence was defined as follow-up PSA >0.4 ng/mL or
      biopsy-proven local recurrence. Systemic progression was defined as development
      of metastatic disease on imaging. Comparisons of baseline characteristics between
      pT0 and non-pT0 groups were carried out using chi-squared tests. Recurrence-free
      survival was estimated using the Kaplan-Meier method and compared using the log
      rank test. RESULTS: A total of 62 patients (0.3%) had pT0 disease according to
      the RP specimen. In univariable analysis, pT0 disease was significantly
      associated with older age (P = 0.045), lower prostate-specific antigen (PSA; P =
      0.002), lower clinical stage (P < 0.001), lower biopsy Gleason score (P = 0.042),
      and receipt of preoperative transurethral resection, hormonal and radiation
      therapies (all P < 0.001). In multivariable analysis, lower PSA levels, lower
      Gleason score, and receipt of preoperative treatment were independently
      associated with pT0 (all P < 0.05). Seven patients (11%) with pT0 PCa developed
      disease recurrence over a median follow-up of 10.9 years. All seven patients had
      preoperative treatment(s) and three had recurrence with a PSA doubling time of <9
      months. Compared with non-pT0 disease, pT0 disease was associated with longer
      recurrence-free survival (P < 0.05). Only one (1.6%) patient with pT0 disease
      developed systemic progression. CONCLUSIONS: pT0 stage PCa is a rare phenomenon
      and is associated with receipt of preoperative treatment and features of low-risk
      PCa. Although pT0 has a very favourable prognosis, some men, especially those who
      received preoperative treatment, experience a small but non-negligible risk of
      disease recurrence and systemic progression.

PMID- 26305997
TI  - Occupational heat-related illness emergency department visits and inpatient
      hospitalizations in the southeast region, 2007-2011.
AB  - BACKGROUND: Heat-related illness (HRI) is an occupational health risk for many
      outdoor, and some indoor, workers. METHODS: Emergency department (ED) and
      inpatient hospitalization (IH) data for 2007-2011 from nine southeast states were
      analyzed to identify occupational HRI numbers and rates, demographic
      characteristics, and co-morbid conditions. RESULTS: There were 8,315 occupational
      HRI ED visits (6.5/100,000 workers) and 1,051 IHs (0.61/100,000) in the southeast
      over the study period. Out-of-state residents comprised 8% of ED visits and 12%
      of IHs. Rates for both, ED visits and IHs were significantly elevated in males
      and blacks. Younger workers had elevated rates for ED visits, while older workers
      had higher IH rates. CONCLUSIONS: This is the first study to evaluate
      occupational HRI ED visits and IHs in the southeast region and indicates the need
      for enhanced heat-stress prevention policies in the southeast. Findings from this
      study can be used to direct state health department tracking and evaluation of
      occupational HRI.

PMID- 26305999
TI  - Neuropsychological and imaging profile of patients with Parkinson's disease and
      freezing of gait.
AB  - BACKGROUND: Neuropsychological evaluation with advanced neuroimaging may be a
      useful tool to determine the anatomical substrates that play crucial role in
      freezing of gait (FOG) in patients with Parkinson's Disease (PD). OBJECTIVES: To
      compare the cognitive profile and gray matter (GM) changes (using Voxel Based
      Morphometry - VBM) between patients with PD with and without FOG (FOG+ve and FOG
      ve). METHODS: Seventeen FOG+ve (M:F = 11:6) and 21 FOG-ve (M:F = 11:10) were
      evaluated clinically and with a structured neuropsychological battery. All
      patients underwent 3 T MRI. In order to determine areas of GM atrophy, T1W
      volumetric MRI data of the two groups were compared using VBM and Statistical
      Parametric Mapping 8. RESULTS: The mean age of FOG+ve and FOG-ve patients were
      56.9 +/- 6.6 and 47.4 +/- 9.1 years respectively. There was no significant
      difference in the duration (6.0 +/- 4.9 vs 5.2 +/- 3.5 years, p < 0.05) and stage
      of PD (Hoehn & Yahr stage: 1.96 +/- 0.53 vs 1.78 +/- 0.37) between the two
      groups. Compared to the FOG-ve group, the FOG+ve group had (i) significant
      impairment in memory, attention, executive and visuospatial functions on
      neuropsychological tests, and (ii) significant GM atrophy in the right cerebellum
      (pyramis, declive), left cerebrum (Brodmann area (BA) 21 and 22) and right
      cerebrum (BA 10 and 6) on VBM analysis. CONCLUSIONS: The FOG+ve group showed
      widespread involvement of cognition localizing to frontal, temporal (especially
      left) and parietal areas. VBM analysis showed significant GM atrophy in FOG+ve
      group in left temporal, right frontal areas (coinciding with that observed in
      neuropsychological tests) and significant involvement of right cerebellum.

PMID- 26305998
TI  - Diagnosing dementia in multiple system atrophy by applying Movement Disorder
      Society diagnostic criteria for Parkinson's disease dementia.
AB  - INTRODUCTION: Dementia is an exclusion criterion in current consensus diagnostic
      criteria, while growing evidence suggests the occurrence of cognitive dysfunction
      and even dementia in multiple system atrophy (MSA) patients. The main goal of
      this study was to determine if Movement Disorder Society (MDS) Parkinson's
      disease dementia (PDD) LEVEL-1 criteria are useful in screening for dementia in
      MSA patients compared to full cognitive testing (LEVEL-2 criteria). METHODS: In
      this retrospective study, MDS diagnostic criteria for PDD were applied in 111 MSA
      patients from three centres. LEVEL-1 evaluation (short screening test) was
      compared to LEVEL-2 examination (extensive neuropsychological gold standard
      assessment). Sensitivity, specificity, positive and negative predictive values
      were calculated for LEVEL-1 compared to LEVEL-2. Two Mini Mental State
      Examination (MMSE) cut-off scores were evaluated (<26 according to MDS procedures
      for the diagnosis of PDD and <27 which has proven more sensitive in a recent
      study proposing a short procedure for PDD screening). RESULTS: According to these
      criteria, 11.7% of MSA patients were demented on LEVEL-2 examination. LEVEL-1
      examination showed strong specificity (96.9%) and negative predictive value
      (94.1%), while sensitivity (53.8%) and positive predictive (70%) value were
      moderate compared to LEVEL-2 evaluation. Sensitivity increased to 84.6% when
      using a MMSE threshold <27 for LEVEL-1. Executive dysfunction was the main
      prevalent finding (52% of all patients), while impairment of memory (15%),
      language (14%) and visuospatial functions was less frequent (13%). CONCLUSION:
      Our findings suggest that the MDS PDD short screening test may be useful for the
      diagnosis of MSA dementia.

PMID- 26306000
TI  - Deep brain stimulation may reduce the relative risk of clinically important
      worsening in early stage Parkinson's disease.
AB  - BACKGROUND: The Vanderbilt pilot trial of deep brain stimulation (DBS) in early
      Parkinson's disease (PD) enrolled patients on medications six months to four
      years without motor fluctuations or dyskinesias. We conducted a patient-centered
      analysis based on clinically important worsening of motor symptoms and
      complications of medical therapy for all subjects and a subset of subjects with a
      more focused medication duration. Continuous outcomes were also analyzed for this
      focused cohort. METHODS: A post hoc analysis was conducted on all subjects from
      the pilot and a subset of subjects taking PD medications 1-4 years at enrollment.
      Clinically important worsening is defined as both a >= 3 point increase in UPDRS
      Part III and a >= 1 point increase in Part IV. RESULTS: DBS plus optimal drug
      therapy (DBS + ODT) subjects experienced a 50-80% reduction in the relative risk
      of worsening after two years. The DBS + ODT group was improved compared to
      optimal drug therapy (ODT) at each time point on Total UPDRS and Part III (p =
      0.04, p = 0.02, respectively, at 24 months). Total UPDRS, Part IV, and PDQ-39
      scores significantly worsened in the ODT group after two years (p < 0.003), with
      no significant change in the DBS + ODT group. CONCLUSIONS: DBS + ODT in early PD
      may reduce the risk of clinically important worsening. These findings further
      confirm the need to determine if DBS + ODT is superior to medical therapy for
      managing symptoms, reducing the complications of medications, and improving
      quality of life. The FDA has approved the conduct of a large-scale, pivotal
      clinical trial of DBS in early stage PD.

PMID- 26306001
TI  - Clinical and imaging markers in premotor LRRK2 G2019S mutation carriers.
AB  - BACKGROUND: Substantia nigra hyperechogenicity (SN+) has been proposed as a risk
      marker of Parkinson's disease (PD). Asymptomatic LRRK2 mutation carriers
      (aLRRK2+), at high risk for developing PD, provide an opportunity for the study
      of preclinical biomarkers. OBJECTIVE: To assess SN echogenicity and other
      echographic features in LRRK2 G2019S carriers and their clinical and imaging
      correlates. METHODS: Transcranial sonography was performed in 26 LRRK2 G2019S PD
      patients, 50 first-degree relatives, 31 idiopathic PD (IPD) patients and 26
      controls. SN echogenicity and other echographic features were assessed in all
      study subjects. Dopamine transporter imaging (DAT-SPECT) was performed in 29
      first-degree relatives. RESULTS: 75% of the LRRK2-PD and 87.5% of the IPD showed
      SN+ (p = 0.087). aLRRK2+ had a higher frequency of SN+ than non carriers (58.3%
      vs. 25%, p = 0.039) and controls (58.3% vs. 12.5%; p = 0.002) and had a larger
      area of SN echogenicity than non carriers (p = 0.030) and controls (p < 0.001).
      The width of the third ventricle was significantly lower in LRRK2-PD than in IPD
      (1.9 mm [1.38; 2.75] vs. 3.0 mm [2.3; 5.3]; p = 0.003). Four out of 5 (80%) of
      the aLRRK2+ with an abnormal DAT-SPECT and four of the 5 (80%) of those with REM
      sleep behaviour disorder (RBD) had SN+. CONCLUSIONS: SN+ is very frequent in
      LRRK2-PD and aLRRK2+. Most aLRRK2 with possible surrogate markers of PD such as
      abnormal DAT-SPECT or RBD, also had SN+, which supports that this echofeature
      might be a marker of PD in these asymptomatic population.

PMID- 26306002
TI  - The effects of graded levels of calorie restriction: IV. Non-linear change in
      behavioural phenotype of mice in response to short-term calorie restriction.
AB  - Animals have to adjust their activities when faced with caloric restriction (CR)
      to deal with reduced energy intake. If CR is pronounced, allostasis can push
      individuals into alternate physiological states which can result in important
      health benefits across a wide range of taxa. Here we developed a new approach to
      determine the changes in behavioural phenotype associated with different levels
      of CR. We exposed C57BL/6 male mice to graded CR (from 0 to 40%) for three months
      and defined their behavioural phenotype using hidden Markov models of their
      movement and body temperature. All 40% CR mice exhibited a state-shift in
      behavioural phenotype and only some exposed to 30% CR did. We show for the first
      time that mice changed their activity characteristics rather than changed their
      activities. This new phenotyping approach provides an avenue to determine the
      mechanisms linking CR to healthspan. 

PMID- 26306003
TI  - E,E-alpha-Farnesene rich essential oil of Saraca asoca (Roxb.) Wilde flower.
AB  - Saraca asoca (Roxb.) Wilde (Fabaceae) commonly known as 'Ashoka' is a highly
      valued medicinal plant categorised 'vulnerable' by International Union for
      Conservation of Nature. The hydro-distilled essential oil from the flowers of S.
      asoca was investigated using gas chromatography equipped with a flame ionisation
      detector (GC-FID) and gas chromatography coupled with a mass spectrometry
      (GC/MS). Twenty-eight compounds representing 95.8% of the total oil were
      identified. The major constituents of the essential oil were E,E-alpha-farnesene
      (41.2%), hexadecanoic acid (15.3%), methyl salicylate (9.5%) and Z-lanceol
      (6.6%). The oil was found to be rich in sesquiterpene hydrocarbon-type
      constituents. 

PMID- 26306004
TI  - INTER- AND INTRAOBSERVER AGREEMENT FOR DIAGNOSING PRESUMPTIVE ISCHEMIC MYELOPATHY
      AND ACUTE NONCOMPRESSIVE NUCLEUS PULPOSUS EXTRUSION IN DOGS USING MAGNETIC
      RESONANCE IMAGING.
AB  - Ischemic myelopathy (IM) and acute noncompressive nucleus pulposus extrusion
      (ANNPE) are common spinal emergencies in dogs with similar clinical
      presentations. Magnetic resonance imaging (MRI) criteria for a presumptive
      antemortem diagnosis have been reported, however inter- and intraobserver
      agreement for use of these criteria has not been established. The aim of this
      retrospective, descriptive, cross-sectional study was to describe inter- and
      intraobserver agreement for using previously published MRI criteria to diagnose
      presumptive IM and ANNPE in a sample dogs. Dogs with a presumptive diagnosis of
      IM or ANNPE and available MRI scan data were retrieved from medical record
      archives during the period of 2009 and 2013. A total of 127 dogs were identified.
      From this sample, MRI scans for 60 dogs were randomly selected and duplicated for
      intraobserver analysis, giving a total of 187 anonymized studies that were
      presented to two blinded assessors (one board-certified veterinary neurologist,
      one board-certified veterinary radiologist). Assessors were asked to diagnose
      lesions as IM or ANNPE based on previously published MRI characteristics.
      Interobserver agreement in diagnosing IM or ANNPE was moderate (Kappa = 0.56) and
      intraobserver agreement was moderate to good (Assessor 1 Kappa = 0.79, Assessor 2
      Kappa = 0.47). Agreement was strongest for detecting presence of lesions
      overlying a vertebral body (94% of lesions that were diagnosed as IM) or
      overlying an intervertebral disk (85% of lesions that were diagnosed as ANNPE).
      Findings indicated that use of previously published MRI criteria yields moderate
      inter- and moderate to good intraobserver agreement for a presumptive diagnosis
      of IM or ANNPE in dogs. 

PMID- 26306005
TI  - An Aza-Cope Reactivity-Based Fluorescent Probe for Imaging Formaldehyde in Living
      Cells.
AB  - Formaldehyde (FA) is a reactive carbonyl species (RCS) produced in living systems
      that has been implicated in epigenetics as well as in the pathologies of various
      cancers, diabetes, and heart, liver, and neurodegenerative diseases. Traditional
      methods for biological FA detection rely on sample destruction and/or extensive
      processing, resulting in a loss of spatiotemporal information. To help address
      this technological gap, we present the design, synthesis, and biological
      evaluation of a fluorescent probe for live-cell FA imaging that relies on a FA
      induced aza-Cope rearrangement. Formaldehyde probe-1 (FAP-1) is capable of
      detecting physiologically relevant concentrations of FA in aqueous buffer and in
      live cells with high selectivity over potentially competing biological analytes.
      Moreover, FAP-1 can visualize endogenous FA produced by lysine-specific
      demethylase 1 in a breast cancer cell model, presaging the potential utility of
      this chemical approach to probe RCS biology. 

PMID- 26306006
TI  - LASSBio-1829 Hydrochloride: Development of a New Orally Active N-Acylhydrazone
      IKK2 Inhibitor with Anti-inflammatory Properties.
AB  - Inhibitor of nuclear factor kappaB kinase 2 (IKK2) is suggested to be a potential
      target for the development of novel anti-inflammatory and anticancer drugs. In
      this work, we applied structure-based drug design to improve the potency of the
      inhibitor (E)-N'-(4-nitrobenzylidene)-2-naphthohydrazide (LASSBio-1524, 1 a: IC50
      =20 MUm). The molecular model built for IKK2 together with the docking
      methodology employed were able to provide important and consistent information
      with respect to the structural and chemical inhibitor characteristics that may
      confer potency to IKK2 inhibitors, providing important guidelines for the
      development of a new N-acylhydrazone (NAH) derivative. (E)-N'-(4-(1H-pyrrolo[2,3
      b]pyridin-4-yl)benzylidene)-2-naphthohydrazide hydrochloride (LASSBio-1829
      hydrochloride, 10) is a 7-azaindole NAH able to inhibit IKK2 with an IC50 value
      of 3.8 MUm. LASSBio-1829 hydrochloride was found to be active in several
      pharmacological inflammation tests in vivo, showing its potential as an anti
      inflammatory prototype.

PMID- 26306009
TI  - [Discrepancy between clinical data and approval documents].
AB  - Pacemakers, ICDs and stents are now playing a major role in cardiology. Again and
      again, however, there are reports of malfunctions and related deaths. Researchers
      have now compared the study results of cardiac high-risk products in the
      registration documents of the US Food and Drug Administration with peer-reviewed
      publications.

PMID- 26306007
TI  - Design of HIV-1 Protease Inhibitors with Amino-bis-tetrahydrofuran Derivatives as
      P2-Ligands to Enhance Backbone-Binding Interactions: Synthesis, Biological
      Evaluation, and Protein-Ligand X-ray Studies.
AB  - Structure-based design, synthesis, and biological evaluation of a series of very
      potent HIV-1 protease inhibitors are described. In an effort to improve backbone
      ligand-binding site interactions, we have incorporated basic-amines at the C4
      position of the bis-tetrahydrofuran (bis-THF) ring. We speculated that these
      substituents would make hydrogen bonding interactions in the flap region of HIV-1
      protease. Synthesis of these inhibitors was performed diastereoselectively. A
      number of inhibitors displayed very potent enzyme inhibitory and antiviral
      activity. Inhibitors 25f, 25i, and 25j were evaluated against a number of highly
      PI-resistant HIV-1 strains, and they exhibited improved antiviral activity over
      darunavir. Two high resolution X-ray structures of 25f- and 25g-bound HIV-1
      protease revealed unique hydrogen bonding interactions with the backbone carbonyl
      group of Gly48 as well as with the backbone NH of Gly48 in the flap region of the
      enzyme active site. These ligand-binding site interactions are possibly
      responsible for their potent activity. 

PMID- 26306010
TI  - [Diabetes mellitus: Which risks do smartphone apps have?].
AB  - Medical apps are increasingly used by patients and doctors. However, it lacks
      systematic studies that deal with potential hazards. In a recent study, two
      thirds of the examined insulin bolus calculator apps were associated with some
      major risks for the patient.

PMID- 26306008
TI  - Non-synonymous FGD3 Variant as Positional Candidate for Disproportional Tall
      Stature Accounting for a Carcass Weight QTL (CW-3) and Skeletal Dysplasia in
      Japanese Black Cattle.
AB  - Recessive skeletal dysplasia, characterized by joint- and/or hip bone
      enlargement, was mapped within the critical region for a major quantitative trait
      locus (QTL) influencing carcass weight; previously named CW-3 in Japanese Black
      cattle. The risk allele was on the same chromosome as the Q allele that increases
      carcass weight. Phenotypic characterization revealed that the risk allele causes
      disproportional tall stature and bone size that increases carcass weight in
      heterozygous individuals but causes disproportionately narrow chest width in
      homozygotes. A non-synonymous variant of FGD3 was identified as a positional
      candidate quantitative trait nucleotide (QTN) and the corresponding mutant
      protein showed reduced activity as a guanine nucleotide exchange factor for
      Cdc42. FGD3 is expressed in the growth plate cartilage of femurs from bovine and
      mouse. Thus, loss of FDG3 activity may lead to subsequent loss of Cdc42 function.
      This would be consistent with the columnar disorganization of proliferating
      chondrocytes in chondrocyte-specific inactivated Cdc42 mutant mice. This is the
      first report showing association of FGD3 with skeletal dysplasia. 

PMID- 26306012
TI  - [85-year old man with swelling on the upper leg 3 years after vascular surgery].

PMID- 26306011
TI  - [How efficient and safe are Vena-cava-filters?].
AB  - In the last 30 years patients with pulmonary embolism have increasingly often
      been implanted with a vena cava filter. Evidence of safety and efficacy in
      comparison to pure anticoagulation are in short supply. Re-removable filter
      reduces neither the risk of recurrence nor mortality, according to a study now
      revealed.

PMID- 26306013
TI  - [The multifaceted importance of orderly sleep: sleep and sleep disorders].

PMID- 26306014
TI  - [Sleep disorders: principles, basic diagnostics and elementary measures and
      recommendations].
AB  - Sleep disorders are frequent. Economic costs and impairment of quality of life
      can be substantial. Usually, patients suffer from insomnia or hypersomnia.
      Several effective therapeutic options are available. Sleep disorders appear
      independently or accompany a multitude of organic and psychiatric diseases.
      Fatigue has to be distinguished from sleep disorders clearly. For classification,
      the ICSD-3, published by the American Academy of Sleep Medicine, is used.
      Patients should be explicitly asked for their sleep quality, for many do not
      report actively. Patient's history and clinical examination usually narrow the
      diagnosis to a large extent. Clinical diagnostics should be carried out according
      to the diagnostic algorithm by the German Sleep Society (DGSM). An optimal sleep
      hygiene and if necessary weight reduction are crucial and can prevent
      chronification and health consequences. In addition, assistive technology, drug
      therapy, behaviour therapy, and in few cases surgery are available. 

PMID- 26306015
TI  - [Sleep-disordered breathing and cardiac disease].
AB  - The prevalence of sleep-disordered breathing (SDB) is ca. 30 % in patients with
      coronary heart disease, ca. 30 % in patients with Hypertonus, ca. 50 % in
      patients with congestive heart failure and ca. 60 % in patients with atrial
      fibrillation. In patients with resistent hypertension, prevalence of SDB is about
      80 %. However, patients with SDB and associated cardiac disease like atrial
      fibrillation or congestive heart failure do not report daytime symptoms like
      excessive daytime sleepiness. Ambulatory cardiorespiratory polygraphy is used to
      screen for SDB in patients with cardiac disease. An effective treatment of SDB
      can reduced blood pressure and can avoid arrhythmias. The effect of treatment of
      SDB in patients with congestive heart failure is currently investigated in
      clinical randomized trials.

PMID- 26306016
TI  - [On the detrimental metabolic impact of short, disturbed and erratic sleep].
AB  - Our modern 24-hour society shows an increasing trend towards shortened and
      erratic sleep.  A large number of epidemiological studies indicate that in
      parallel, the prevalence of the metabolic syndrome and its key components,
      obesity and type 2 diabetes mellitus, is on the rise. Short-term interventional
      experiments point to a causal relationship between sleep duration and quality and
      energy metabolism and have identified underlying mechanisms. In particular,
      changes in the neuroendocrine regulation of glucose metabolism, in circadian
      rhythmicity as well as in the regulation of appetite and eating behavior are
      assumed to mediate the detrimental effect of insufficient sleep on energy
      balance. Although long-term interventional studies are still sparse, existing
      evidence suggests that improving sleep hygiene represents an attractive approach
      for the prevention and treatment of metabolic diseases.

PMID- 26306017
TI  - [Insertable Cardiac Monitor].
AB  - Intermittent cardiac arrhythmias are sometimes difficult to register using
      conventional detection concepts. The implantable event recorders offer a unique
      opportunity to document short lasting or rare and even asymptomatic arrhythmias.
      This manuscript describes event recorder implantation in a step-by-step manner. 

PMID- 26306018
TI  - [Progressive multifocal leukoencephalopathy following azathioprine and steroid
      treatment of pulmonary sarcoid disease].
AB  - Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of
      the central nervous system following reactivation of the John-Cunningham-Virus
      (JVC) in an immunocompromised host. This rare condition is characterized by rapid
      progressing neurologic symptoms often leading to death. In the following, we
      report on a rapid evolving deterioration of mental status due to PML in an 53
      year-old man during treatment of pulmonary sarcoid disease using azathioprine and
      steroids. In contrast to reported lethal outcomes, our patient experienced a slow
      recovery of his cognitive impairment and later on of his palsy following
      termination of immunosuppression. 

PMID- 26306019
TI  - [Diagnosis and differential diagnosis of Cushing's syndrome].

PMID- 26306020
TI  - ["Good dying"--definition and current state of research].
AB  - The advances of modern medicine did not only result in prolongation of life
      expectancy, but also led to a shift from dying at home to dying in public
      institutions. In western countries most people die at advanced age in medical
      facilities. Hence, the question regarding the conditions, which should be
      provided by society and especially medicine, to allow terminally ill people to
      experience "good dying" is substantial. For this purpose, an examination of
      patients', family members' and health care providers' understanding of the term "
      good dying" is required. The present paper aims at shedding light on the term
      "good dying" and to summarize the current state of research. Therefore, the
      attributes of "good dying" will be described from the perspectives of patients,
      family members and health care providers, which are discussed and examined in
      current medical-sociological research. These attributes can be illustrated on
      three dimensions: Quality of life at the end of life (e. g. pain relief, mental
      well-being), quality of dying (e. g. avoiding prolonged dying, autonomy, presence
      of relatives) and quality of health care at the end of life (e. g. patient
      oriented health care, positive communication between health care providers and
      patients, availability of guidelines). Although the attributes of "good dying"
      are described in detail in the existing literature, further studies have to
      clarify the relevance and impact of these attributes as predictors of "good
      dying". 

PMID- 26306021
TI  - [Hemolytic anemias and vitamin B12 deficieny].
AB  - Hemolytic anemias consist of corpuscular, immun-hemolytic and toxic hemolytic
      anemias. Within the group of corpuscular hemolytic anemias, except for the
      paroxysmal nocturnal hemoglobinuria (PNH), all symptoms are caused by underlying
      heredetiary disorders within the red blood cell membran (hereditary
      spherocytosis), deficiencies of red cell enzymes (G6PDH- and pyrovatkinase
      deficiency) or disorders in the hemoglobin molecule (thalassaemia and sickle cell
      disease). Immune-hemolytic anemias are acquired hemolytic anemias and hemolysis
      is caused by auto- or allo-antibodies which are directed against red blood cell
      antigens. They are classified as warm, cold, mixed type or drug-induced hemolytic
      anemia. Therapy consists of glucocorticoids and other immunsuppressive drugs.
      Pernicious anemia is the most important vitamin B12 deficiency disorder.
      Diagnosis relies on cobalamin deficiency and antibodies to intrinsic factor. The
      management should focus on a possibly life-long replacement treatment with
      cobalamin. 

PMID- 26306022
TI  - [What is the use of even lower LDL cholesterol by combination therapy? A critical
      viewpoint].
AB  - The IMPROVE-IT study has demonstrated a significant reduction of LDL-C when
      ezetimibe was given in addition to statins. Although the number of strokes and MI
      was reduced after 7 to 10 years of this treatment, mortality was unaffected,
      however. Additive ezetimibe treatment can be recommended only, if a better or
      longer life has been proved - which is not the case. 

PMID- 26306023
TI  - [Ill or not ill? Towards a better management of patients with "medically
      unexplained symptoms"].

PMID- 26306024
TI  - [Renal impairment in patients with thromboembolic event: prevalence and clinical
      implications. A systematic review of the literature].
AB  - BACKGROUND AND STUDY OBJECTIVES: The assessment of the renal function of patients
      with a deep vein thrombosis/pulmonary embolism (VTE patients) is of utmost
      importance for the selection/dosage of an agent in the initial anticoagulation
      management of these patients because the majority of available anticoagulants are
      cleared renally. Specifically, there is a high risk of drug accumulation and
      subsequent bleedings in patients with severe renal insufficiency. Consequently,
      specific recommendations have been made for the initial anticoagulation
      management of these patients in both product labels and AWMF treatment
      recommendations: some drugs should not be used in these patients, for other drugs
      a careful use, intensified screening (anti-Xa), or, in the case of enoxaparin, a
      dose-adjustment are recommended.This literature review aimed to answer the
      following questions: . What is the prevalence of renal insufficiency in VTE
      patients?. . Which data are available with regard to the real-world initial
      anticoagulation management and corresponding clinical outcomes (recurrent VTE
      events, bleedings, mortality) of these patients? METHODOLOGY: We did a systematic
      review of existing publications in german or english published in 2004-2014. Only
      quantitative analyses have been included in the review. RESULTS: We identified
      1,135 publications, 37 of them were included in our review. The prevalence of
      renal insufficiency in VTE patients, defined as CrCl < 60 ml / min, was reported
      to be 12.3 %-71.9 % related to all VTE patients. The prevalence of severe renal
      insufficiency, defined as CrCl < 30 ml / min, was reported to be 3,3 %-13,6 %.
      The substantial ranges in reported prevalences are mainly due to differences in
      the characteristics of patients addressed in the different publications.A CrCl <
      30 ml / min is an independent predictor for both mortality and lethal recurrent
      pulmonary embolism, possibly also for severe bleedings in VTE patients. In
      addition to that, a severe renal insufficiency may also be a predictor for the
      probability that a first VTE event occurs.Several anticoagulants approved for the
      initial anticoagulation management of VTE patients face the risk of drug
      accumulation in renally insufficent patients. So, for example, a standard
      enoxaparin dosage was shown to be associated with elevated bleeding risk compared
      to adjusted enoxaparin dosage in renally insufficient patients. However, similar
      data do not exist for other low molecular weight heparins (LMWHs) or unfractioned
      heparins (UFHs). Only for two LMWHs, Certoparin and Tinzaparin, safety data with
      regard to renally insufficient patients have been published so far.None of the
      included studies showed advantages of UFH therapy in comparison to LMWH therapy
      in initial anticoagulation management of VTE patients. In contrast to that,
      available evidence shows disadvantageous efficacy/safety of UFH in comparison to
      LMWH treatment. However, this evidence is not based on head-to-head comparisons
      but is derived from registry and observational study data only. CONCLUSION: A
      detailed knowledge of product labels is of utmost importance in the inital
      anticoagulation treatment of VTE patients because several agents may not be used
      in the addressed patients with severe renal insufficiency at all while others may
      be used based on specific dosage/surveillance schemes only. We also recommend to
      critically appraise the current AWMF treatment guideline because it still
      recommends initial anticoagulation management with UFHs in VTE patients with
      severe renal insufficiency. Available data do not support that recommendation.

PMID- 26306025
TI  - [39-year-old man with 15 years lasting pain in both hands].
AB  - In the article "39-year-old patient with years of pain in both hands" (Dtsch Med
      Wochenschr 2015; 140: 1231) have called the names of the authors Klaus
      Muehlenberg, Claudia Metzler and Oliver Pech.

PMID- 26306026
TI  - Preparation, Characterization, and In Vivo Study of 7-Ethyl-14-Aminocamptothecin
      Loaded Poly(Ethylene Glycol)2000 -Poly(Lactic Acid)2000 Polymeric Micelles
      Against H460 Human Nonsmall Cell Lung Carcinoma.
AB  - This work aims to improve the solubility of 7-ethyl-14-aminocamptothecin (EACPT)
      by encapsulating it into monomethoxy poly(ethylene glycol)2000 -poly(lactic
      acid)2000 (MPEG-PLA) polymeric micelles. Micelles were prepared by a solid
      dispersion method; the properties including particle size distribution,
      morphology, drug loading, entrapment efficiency, crystallography property,
      solubility, and stability were characterized in detail. The results demonstrated
      that the EACPT-loaded MPEG-PLA polymeric micelle (EACPT-M) was successfully
      developed with a small particle size of 20.7 +/- 0.2 nm, and the solubility was
      increased approximately 800-fold compared with free drug. In vitro release study
      showed sustained-release behavior of EACPT-M. Cytotoxicity assay suggested the
      incorporated EACPT maintained the potent antitumor effect of free drug.
      Furthermore, the obtained EACPT-M (1 mg/mL) did not induce hemolysis in vitro.
      Additionally, EACPT-M exhibited significant tumor growth inhibition in H460 human
      tumor xenograft model. The results indicated that the EACPT-M was a water
      soluble, safe, and effective delivery system for human cancer chemotherapy.

PMID- 26306027
TI  - Atomically flat ultrathin cobalt ferrite islands.
AB  - A route for fabricating structurally perfect cobalt ferrite magnetic
      nanostructures is demonstrated. Ultrathin islands of up to 100 MUm(2) with
      atomically flat surfaces and free from antiphase boundaries are developed. The
      extremely low defect concentration leads to a robust magnetic order, even for
      thicknesses below 1 nm, and exceptionally large magnetic domains. This approach
      allows the evaluation of the influence of specific extrinsic effects on domain
      wall pinning. 

PMID- 26306028
TI  - Using the electronic medical record to assess contraception usage among women
      taking category D or X medications.
AB  - BACKGROUND: The aim of this study is to investigate contraceptive usage among
      women prescribed or currently taking a category D or X medication using the
      electronic medical record. METHODS: This is a retrospective study assessing
      contraceptive usage among women prescribed category D or X medications. We
      obtained access to the electronic medical records of women seen in an academic
      Family Medicine Department between April 2011 and April 2012 who were prescribed
      a category D or X medication. Information was abstracted regarding the specific
      category D or X medication, demographics, sexual activity, sexual partner gender,
      and contraceptive usage. RESULTS: There were a total of 610 women included in
      this study. Among the 610 women, 72 (11.8%) of women had documentation that they
      were not asked about their sexual activity. Sexual activity with men was
      documented in 407 of the 610 women (66.7%). Of these 407 women, 132 (32.4%) had
      no contraceptive method documented. Among the women using contraception, the most
      common method used was oral contraception. CONCLUSION: According to data obtained
      from the electronic medical record, women who are taking a category D or X
      medication are not always asked about sexual activity. Contraception usage among
      women taking category D or X medications and who were sexually active with men
      was similar to the general population. Contraception usage should be better in
      this population given the risk of an unintended pregnancy includes fetal exposure
      to a potential teratogen. The electronic medical record creates an opportunity
      for an intervention to increase contraception utilization in this population.

PMID- 26306029
TI  - Brain activity during walking: A systematic review.
AB  - BACKGROUND: This systematic review provides an overview of the literature
      deducing information about brain activation during (1) imagined walking using
      MRI/fMRI or (2) during real walking using measurement systems as fNIRS, EEG and
      PET. METHODS: Three independent reviewers undertook an electronic database
      research browsing six databases. The search request consisted of three search
      fields. The first field comprised common methods to evaluate brain activity. The
      second search field comprised synonyms for brain responses to movements. The
      third search field comprised synonyms for walking. RESULTS: 48 of an initial
      yield of 1832 papers were reviewed. We found differences in cortical activity
      regarding young vs. old individuals, physically fit vs. physically unfit cohorts,
      healthy people vs. patients with neurological diseases, and between simple and
      complex walking tasks. CONCLUSIONS: We summarize that the dimension of brain
      activity in different brain areas during walking is highly sensitive to task
      complexity, age and pathologies supporting previous assumptions underpinning the
      significance of cortical control. Many compensation mechanisms reflect the
      brain's plasticity which ensures stable walking.

PMID- 26306030
TI  - A Bisbenzamidine Phosphonate as a Janus-faced Inhibitor for Trypsin-like Serine
      Proteases.
AB  - A hybrid approach was applied for the design of an inhibitor of trypsin-like
      serine proteases. Compound 16 [(R,R)- and (R,S)-diphenyl (4-(1-(4
      amidinobenzylamino)-1-oxo-3-phenylpropan-2-ylcarbamoyl)phenylamino)(4
      amidinophenyl)methylphosphonate hydrochloride], prepared in a convergent
      synthetic procedure, possesses a phosphonate warhead prone to react with the
      active site serine residue in a covalent, irreversible manner. Each of the two
      benzamidine moieties of 16 can potentially be accommodated in the S1 pocket of
      the target enzyme, but only the benzamidine close to the phosphonate group would
      then promote an irreversible interaction. The Janus-faced inhibitor 16 was
      evaluated against several serine proteases and caused a pronounced inactivation
      of human thrombin with a second-order rate constant (kinac /Ki) of 59 500 M(-1) 
      s(-1). With human matriptase, 16 showed preference for a reversible mode of
      inhibition (IC50 =2.6 MUM) as indicated by linear progress curves and enzyme
      reactivation.

PMID- 26306031
TI  - The Cell Shape-determining Csd6 Protein from Helicobacter pylori Constitutes a
      New Family of L,D-Carboxypeptidase.
AB  - Helicobacter pylori causes gastrointestinal diseases, including gastric cancer.
      Its high motility in the viscous gastric mucosa facilitates colonization of the
      human stomach and depends on the helical cell shape and the flagella. In H.
      pylori, Csd6 is one of the cell shape-determining proteins that play key roles in
      alteration of cross-linking or by trimming of peptidoglycan muropeptides. Csd6 is
      also involved in deglycosylation of the flagellar protein FlaA. To better
      understand its function, biochemical, biophysical, and structural
      characterizations were carried out. We show that Csd6 has a three-domain
      architecture and exists as a dimer in solution. The N-terminal domain plays a key
      role in dimerization. The middle catalytic domain resembles those of l,d
      transpeptidases, but its pocket-shaped active site is uniquely defined by the
      four loops I to IV, among which loops I and III show the most distinct variations
      from the known l,d-transpeptidases. Mass analyses confirm that Csd6 functions
      only as an l,d-carboxypeptidase and not as an l,d-transpeptidase. The d-Ala
      complexed structure suggests possible binding modes of both the substrate and
      product to the catalytic domain. The C-terminal nuclear transport factor 2-like
      domain possesses a deep pocket for possible binding of pseudaminic acid, and in
      silico docking supports its role in deglycosylation of flagellin. On the basis of
      these findings, it is proposed that H. pylori Csd6 and its homologs constitute a
      new family of l,d-carboxypeptidase. This work provides insights into the function
      of Csd6 in regulating the helical cell shape and motility of H. pylori.

PMID- 26306032
TI  - Prerequisites for Functional Interleukin 31 Signaling and Its Feedback Regulation
      by Suppressor of Cytokine Signaling 3 (SOCS3).
AB  - Interleukin-31 (IL-31) is a T helper type 2 cell-derived cytokine tightly
      associated with inflammatory skin disorders. IL-31-induced signaling is mediated
      by a receptor complex composed of oncostatin M receptor beta and the cytokine
      specific receptor subunit IL-31Ralpha, of which there are several isoforms. The
      latter can be classified as long or short isoforms with respect to their
      intracellular domain. At present, the signaling capabilities of the different
      isoforms remain inchoately understood, and potential mechanisms involved in
      negative regulation of IL-31Ralpha signaling have so far not been studied in
      detail. Here, we show that both the long and short isoforms of IL-31Ralpha are
      capable of inducing STAT signaling. However, the presence of a functional JAK
      binding box within IL-31Ralpha is an essential prerequisite for functional IL-31
      mediated STAT3 signaling. Moreover, both the long and short isoforms require
      oncostatin M receptor beta for their activity. We also show that IL-31 induces
      expression of four suppressor of cytokine signaling family members and provide
      evidence that SOCS3 acts as a potent feedback inhibitor of IL-31-induced
      signaling. Taken together, this study identifies crucial requirements for IL-31
      signaling and shows its counter-regulation by SOCS3.

PMID- 26306033
TI  - The Histone Demethylase UTX Promotes Brown Adipocyte Thermogenic Program Via
      Coordinated Regulation of H3K27 Demethylation and Acetylation.
AB  - Brown adipocytes function to dissipate energy as heat through adaptive
      thermogenesis. Understanding the molecular mechanisms underlying the brown fat
      thermogenic program may provide insights for the development of therapeutic
      approaches in the treatment of obesity. Most studies investigating the mechanisms
      underlying brown fat development focus on genetic mechanisms; little is known
      about the epigenetic mechanisms in this process. We have discovered that
      ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX), a
      histone demethylase for di- or tri-methylated histone 3 lysine 27 (H3K27me2/3),
      plays a potential role in regulating brown adipocyte thermogenic program. We
      found that UTX is up-regulated during brown adipocyte differentiation and by cold
      exposure in both brown adipose tissue (BAT) and white adipose tissue (WAT) of
      mice, suggesting a potential role in thermogenesis. Inactivation of UTX down
      regulates brown fat specific gene expression, while overexpression of UTX does
      the opposite. Notably, activation of beta adrenergic signaling recruits UTX to
      the UCP1 and PGC1alpha promoters, leading to decreased H3K27me3, a histone
      transcriptional repressive mark. UTX demethylates H3K27me3 and subsequently
      interacts with the histone acetyltransferase (HAT) protein CBP, resulting in
      increased H3K27 acetylation (H3K27ac), a histone transcriptional active mark. UTX
      positively regulate brown adipocyte thermogenic program through coordinated
      control of demethylating H3K27me3 and acetylating H3K27, switching the
      transcriptional repressive state to the transcriptional active state at the
      promoters of UCP1 and PGC1alpha. We conclude that UTX may play a potential role
      in regulation of brown adipocyte gene expression and may mediate beta adrenergic
      activation of brown fat function.

PMID- 26306034
TI  - Functional Roles of Clusters of Hydrophobic and Polar Residues in the Epithelial
      Na+ Channel Knuckle Domain.
AB  - The extracellular regions of epithelial Na(+) channel subunits are highly ordered
      structures composed of domains formed by alpha helices and beta strands. Deletion
      of the peripheral knuckle domain of the alpha subunit in the alphabetagamma
      trimer results in channel activation, reflecting an increase in channel open
      probability due to a loss of the inhibitory effect of external Na(+) (Na(+) self
      inhibition). In contrast, deletion of either the beta or gamma subunit knuckle
      domain within the alphabetagamma trimer dramatically reduces epithelial Na(+)
      channel function and surface expression, and impairs subunit maturation. We
      systematically mutated individual alpha subunit knuckle domain residues and
      assessed functional properties of these mutants. Cysteine substitutions at 14 of
      28 residues significantly suppressed Na(+) self-inhibition. The side chains of a
      cluster of these residues are non-polar and are predicted to be directed toward
      the palm domain, whereas a group of polar residues are predicted to orient their
      side chains toward the space between the knuckle and finger domains. Among the
      mutants causing the greatest suppression of Na(+) self-inhibition were
      alphaP521C, alphaI529C, and alphaS534C. The introduction of Cys residues at
      homologous sites within either the beta or gamma subunit knuckle domain resulted
      in little or no change in Na(+) self-inhibition. Our results suggest that
      multiple residues in the alpha subunit knuckle domain contribute to the mechanism
      of Na(+) self-inhibition by interacting with palm and finger domain residues via
      two separate and chemically distinct motifs.

PMID- 26306035
TI  - Stringent Control of NFE2L3 (Nuclear Factor, Erythroid 2-Like 3; NRF3) Protein
      Degradation by FBW7 (F-box/WD Repeat-containing Protein 7) and Glycogen Synthase
      Kinase 3 (GSK3).
AB  - The NFE2L3 transcription factor has been implicated in various cellular
      processes, including carcinogenesis, stress response, differentiation, and
      inflammation. Previously it has been shown that NFE2L3 has a rapid turnover and
      is stabilized by proteasomal inhibitors. The mechanisms regulating the
      degradation of this protein have not been investigated. Here we report
      ubiquitination of NFE2L3 and demonstrate that F-box/WD repeat-containing protein
      7 (FBW7 or FBWX7), a component of Skp1, Cullin 1, F-box containing complex (SCF)
      type E3 ligase, is the E3 ligase mediating the degradation of NFE2L3. We showed
      that FBW7 interacts with NFE2L3 and that dimerization of FBW7 is required for the
      degradation of the transcription factor. We also demonstrate that the kinase
      glycogen synthase kinase 3 (GSK3) mediates the FBW7-dependent ubiquitination of
      NFE2L3. We show phosphorylation of NFE2L3 by GSK3 and its significance in the
      regulation of NFE2L3 by the tumor suppressor FBW7. FBW7 abrogated NFE2L3-mediated
      repression of the NAD(P)H: quinone oxidoreductase 1 (NQO1) gene antioxidant
      response element (ARE). Our findings reveal FBW7 and GSK3 as novel regulators of
      the NFE2L3 transcription factor and a potential mechanism by which FBW7 might
      regulate detoxification and the cellular response to stress.

PMID- 26306036
TI  - Regulation of plasma membrane localization of the Na+-taurocholate cotransporting
      polypeptide (Ntcp) by hyperosmolarity and tauroursodeoxycholate.
AB  - In perfused rat liver, hepatocyte shrinkage induces a Fyn-dependent retrieval of
      the bile salt export pump (Bsep) and multidrug resistance-associated protein 2
      (Mrp2) from the canalicular membrane (Cantore, M., Reinehr, R., Sommerfeld, A.,
      Becker, M., and Haussinger, D. (2011) J. Biol. Chem. 286, 45014-45029) leading to
      cholestasis. However little is known about the effects of hyperosmolarity on
      short term regulation of the Na(+)-taurocholate cotransporting polypeptide
      (Ntcp), the major bile salt uptake system at the sinusoidal membrane of
      hepatocytes. The aim of this study was to analyze hyperosmotic Ntcp regulation
      and the underlying signaling events. Hyperosmolarity induced a significant
      retrieval of Ntcp from the basolateral membrane, which was accompanied by an
      activating phosphorylation of the Src kinases Fyn and Yes but not of c-Src.
      Hyperosmotic internalization of Ntcp was sensitive to SU6656 and PP-2, suggesting
      that Fyn mediates Ntcp retrieval from the basolateral membrane. Hyperosmotic
      internalization of Ntcp was also found in livers from wild-type mice but not in
      p47(phox) knock-out mice. Tauroursodeoxycholate (TUDC) and cAMP reversed
      hyperosmolarity-induced Fyn activation and triggered re-insertion of the
      hyperosmotically retrieved Ntcp into the membrane. This was associated with
      dephosphorylation of the Ntcp on serine residues. Insertion of Ntcp by TUDC was
      sensitive to the integrin inhibitory hexapeptide GRGDSP and inhibition of protein
      kinase A. TUDC also reversed the hyperosmolarity-induced retrieval of bile salt
      export pump from the canalicular membrane. These findings suggest a coordinated
      and oxidative stress- and Fyn-dependent retrieval of sinusoidal and canalicular
      bile salt transport systems from the corresponding membranes. Ntcp insertion was
      also identified as a novel target of beta1-integrin-dependent TUDC action, which
      is frequently used in the treatment of cholestatic liver disease. 

PMID- 26306037
TI  - Structural Basis for Ca2+-mediated Interaction of the Perforin C2 Domain with
      Lipid Membranes.
AB  - Natural killer cells and cytotoxic T-lymphocytes deploy perforin and granzymes to
      kill infected host cells. Perforin, secreted by immune cells, binds target
      membranes to form pores that deliver pro-apoptotic granzymes into the target
      cell. A crucial first step in this process is interaction of its C2 domain with
      target cell membranes, which is a calcium-dependent event. Some aspects of this
      process are understood, but many molecular details remain unclear. To address
      this, we investigated the mechanism of Ca(2+) and lipid binding to the C2 domain
      by NMR spectroscopy and x-ray crystallography. Calcium titrations, together with
      dodecylphosphocholine micelle experiments, confirmed that multiple Ca(2+) ions
      bind within the calcium-binding regions, activating perforin with respect to
      membrane binding. We have also determined the affinities of several of these
      binding sites and have shown that this interaction causes a significant
      structural rearrangement in CBR1. Thus, it is proposed that Ca(2+) binding at the
      weakest affinity site triggers changes in the C2 domain that facilitate its
      interaction with lipid membranes. 

PMID- 26306038
TI  - The Potato Nucleotide-binding Leucine-rich Repeat (NLR) Immune Receptor Rx1 Is a
      Pathogen-dependent DNA-deforming Protein.
AB  - Plant nucleotide-binding leucine-rich repeat (NLR) proteins enable cells to
      respond to pathogen attack. Several NLRs act in the nucleus; however, conserved
      nuclear targets that support their role in immunity are unknown. Previously, we
      noted a structural homology between the nucleotide-binding domain of NLRs and DNA
      replication origin-binding Cdc6/Orc1 proteins. Here we show that the NB-ARC
      (nucleotide-binding, Apaf-1, R-proteins, and CED-4) domain of the Rx1 NLR of
      potato binds nucleic acids. Rx1 induces ATP-dependent bending and melting of DNA
      in vitro, dependent upon a functional P-loop. In situ full-length Rx1 binds
      nuclear DNA following activation by its cognate pathogen-derived effector
      protein, the coat protein of potato virus X. In line with its obligatory
      nucleocytoplasmic distribution, DNA binding was only observed when Rx1 was
      allowed to freely translocate between both compartments and was activated in the
      cytoplasm. Immune activation induced by an unrelated NLR-effector pair did not
      trigger an Rx1-DNA interaction. DNA binding is therefore not merely a consequence
      of immune activation. These data establish a role for DNA distortion in Rx1
      immune signaling and define DNA as a molecular target of an activated NLR.

PMID- 26306039
TI  - Death-associated Protein 3 Regulates Mitochondrial-encoded Protein Synthesis and
      Mitochondrial Dynamics.
AB  - Mitochondrial morphologies change over time and are tightly regulated by dynamic
      machinery proteins such as dynamin-related protein 1 (Drp1), mitofusion 1/2, and
      optic atrophy 1 (OPA1). However, the detailed mechanisms of how these molecules
      cooperate to mediate fission and fusion remain elusive. DAP3 is a mitochondrial
      ribosomal protein that involves in apoptosis, but its biological function has not
      been well characterized. Here, we demonstrate that DAP3 specifically localizes in
      the mitochondrial matrix. Knockdown of DAP3 in mitochondria leads to defects in
      mitochondrial-encoded protein synthesis and abnormal mitochondrial dynamics.
      Moreover, depletion of DAP3 dramatically decreases the phosphorylation of Drp1 at
      Ser-637 on mitochondria, enhancing the retention time of Drp1 puncta on
      mitochondria during the fission process. Furthermore, autophagy is inhibited in
      the DAP3-depleted cells, which sensitizes cells to different types of death
      stimuli. Together, our results suggest that DAP3 plays important roles in
      mitochondrial function and dynamics, providing new insights into the mechanism of
      a mitochondrial ribosomal protein function in cell death.

PMID- 26306040
TI  - Assembly of the Arp5 (Actin-related Protein) Subunit Involved in Distinct INO80
      Chromatin Remodeling Activities.
AB  - ATP-dependent chromatin remodeling, which repositions and restructures
      nucleosomes, is essential to all DNA-templated processes. The INO80 chromatin
      remodeling complex is an evolutionarily conserved complex involved in diverse
      cellular processes, including transcription, DNA repair, and replication. The
      functional diversity of the INO80 complex can, in part, be attributed to
      specialized activities of distinct subunits that compose the complex.
      Furthermore, structural analyses have identified biochemically discrete subunit
      modules that assemble along the Ino80 ATPase scaffold. Of particular interest is
      the Saccharomyces cerevisiae Arp5-Ies6 module located proximal to the Ino80
      ATPase and the Rvb1-Rvb2 helicase module needed for INO80-mediated in vitro
      activity. In this study we demonstrate that the previously uncharacterized Ies2
      subunit is required for Arp5-Ies6 association with the catalytic components of
      the INO80 complex. In addition, Arp5-Ies6 module assembly with the INO80 complex
      is dependent on distinct conserved domains within Arp5, Ies6, and Ino80,
      including the spacer region within the Ino80 ATPase domain. Arp5-Ies6 interacts
      with chromatin via assembly with the INO80 complex, as IES2 and INO80 deletion
      results in loss of Arp5-Ies6 chromatin association. Interestingly, ectopic
      addition of the wild-type Arp5-Ies6 module stimulates INO80-mediated ATP
      hydrolysis and nucleosome sliding in vitro. However, the addition of mutant Arp5
      lacking unique insertion domains facilitates ATP hydrolysis in the absence of
      nucleosome sliding. Collectively, these results define the requirements of Arp5
      Ies6 assembly, which are needed to couple ATP hydrolysis to productive nucleosome
      movement. 

PMID- 26306041
TI  - Mitochondrial Iron-Sulfur Cluster Activity and Cytosolic Iron Regulate Iron
      Traffic in Saccharomyces cerevisiae.
AB  - An ordinary differential equation-based mathematical model was developed to
      describe trafficking and regulation of iron in growing fermenting budding yeast.
      Accordingly, environmental iron enters the cytosol and moves into mitochondria
      and vacuoles. Dilution caused by increasing cell volume is included. Four sites
      are regulated, including those in which iron is imported into the cytosol,
      mitochondria, and vacuoles, and the site at which vacuolar Fe(II) is oxidized to
      Fe(III). The objective of this study was to determine whether cytosolic iron
      (Fecyt) and/or a putative sulfur-based product of iron-sulfur cluster (ISC)
      activity was/were being sensed in regulation. The model assumes that the matrix
      of healthy mitochondria is anaerobic, and that in ISC mutants, O2 diffuses into
      the matrix where it reacts with nonheme high spin Fe(II) ions, oxidizing them to
      nanoparticles and generating reactive oxygen species. This reactivity causes a
      further decline in ISC/heme biosynthesis, which ultimately gives rise to the
      diseased state. The ordinary differential equations that define this model were
      numerically integrated, and concentrations of each component were plotted versus
      the concentration of iron in the growth medium and versus the rate of ISC/heme
      biosynthesis. Model parameters were optimized by fitting simulations to
      literature data. The model variant that assumed that both Fecyt and ISC
      biosynthesis activity were sensed in regulation mimicked observed behavior best.
      Such "dual sensing" probably arises in real cells because regulation involves
      assembly of an ISC on a cytosolic protein using Fecyt and a sulfur species
      generated in mitochondria during ISC biosynthesis and exported into the cytosol.

PMID- 26306042
TI  - The Kinase Activity-deficient Isoform of the Protein Araf Antagonizes Ras/Mitogen
      activated Protein Kinase (Ras/MAPK) Signaling in the Zebrafish Embryo.
AB  - Raf kinases are important components of the Ras-Raf-Mek-Erk pathway and also
      cross-talk with other signaling pathways. Araf kinase has been demonstrated to
      inhibit TGF-beta/Smad2 signaling by directly phosphorylating and accelerating
      degradation of activated Smad2. In this study, we show that the araf gene
      expresses in zebrafish embryos to produce a shorter transcript variant, araf-tv2,
      in addition to the full-length variant araf-tv1. araf-tv2 is predicted to encode
      a C-terminally truncated peptide without the kinase activity domain. Araf-tv2 can
      physically associate with Araf-tv1 but does not antagonize the inhibitory effect
      of Araf-tv1 on TGF-beta/Smad2 signaling. Instead, Araf-tv2 interacts strongly
      with Kras and Nras, ultimately blocking MAPK activation by these Ras proteins. In
      zebrafish embryos, overexpression of araf-tv2 is sufficient to inhibit Fgf/Ras
      promoted Erk activation, mesodermal induction, dorsal development, and
      neuroectodermal posteriorization. Therefore, different isoforms of Araf may
      participate in similar developmental processes but by regulating different
      signaling pathways. 

PMID- 26306043
TI  - Partially Unfolded Forms of the Prion Protein Populated under Misfolding
      promoting Conditions: CHARACTERIZATION BY HYDROGEN EXCHANGE MASS SPECTROMETRY AND
      NMR.
AB  - The susceptibility of the cellular prion protein (PrP(C)) to convert to an
      alternative misfolded conformation (PrP(Sc)), which is the key event in the
      pathogenesis of prion diseases, is indicative of a conformationally flexible
      native (N) state. In the present study, hydrogen-deuterium exchange (HDX) in
      conjunction with mass spectrometry and nuclear magnetic resonance spectroscopy
      were used for the structural and energetic characterization of the N state of the
      full-length mouse prion protein, moPrP(23-231), under conditions that favor
      misfolding. The kinetics of HDX of 34 backbone amide hydrogens in the N state
      were determined at pH 4. In contrast to the results of previous HDX studies on
      the human and Syrian hamster prion proteins at a higher pH, various segments of
      moPrP were found to undergo different extents of subglobal unfolding events at pH
      4, a pH at which the protein is known to be primed to misfold to a beta-rich
      conformation. No residual structure around the disulfide bond was observed for
      the unfolded state at pH 4. The N state of the prion protein was observed to be
      at equilibrium with at least two partially unfolded forms (PUFs). These PUFs,
      which are accessed by stochastic fluctuations of the N state, have altered
      surface area exposure relative to the N state. One of these PUFs resembles a
      conformation previously implicated to be an initial intermediate in the
      conversion of monomeric protein into misfolded oligomer at pH 4. 

PMID- 26306044
TI  - An E2 accessory domain increases affinity for the anaphase-promoting complex and
      ensures E2 competition.
AB  - The anaphase-promoting complex/cyclosome (APC/C) is a member of the RING family
      of E3 ubiquitin ligases, which promote ubiquitin transfer from an E2 ubiquitin
      conjugating enzyme to a substrate. In budding yeast, the APC/C collaborates with
      two E2s, Ubc4 and Ubc1, to promote the initiation and elongation, respectively,
      of polyubiquitin chains on the substrate. Ubc4 and Ubc1 are thought to compete
      for the same site on the APC/C, but it is not clear how their affinities are
      balanced. Here, we demonstrate that a C-terminal ubiquitin-associated (UBA)
      domain enhances the affinity of Ubc1 for the APC/C. Deletion of the UBA domain
      reduced apparent APC/C affinity for Ubc1 and decreased polyubiquitin chain
      length. Surprisingly, the positive effect of the UBA domain was not due to an
      interaction with the acceptor ubiquitin attached to the APC/C substrate or the
      donor ubiquitin attached to Ubc1 itself. Instead, our evidence suggests that the
      UBA domain binds to a site on the APC/C core, thereby increasing Ubc1 affinity
      and enhancing its ability to compete with Ubc4. The UBA domain is required for
      normal Ubc1 function and E2 competition in vivo. Thus, the UBA domain of Ubc1
      ensures efficient polyubiquitination of substrate by balancing Ubc1 affinity with
      that of Ubc4. 

PMID- 26306046
TI  - Tubulin tail sequences and post-translational modifications regulate closure of
      mitochondrial voltage-dependent anion channel (VDAC).
AB  - It was previously shown that tubulin dimer interaction with the mitochondrial
      outer membrane protein voltage-dependent anion channel (VDAC) blocks traffic
      through the channel and reduces oxidative metabolism and that this requires the
      unstructured anionic C-terminal tail peptides found on both alpha- and beta
      tubulin subunits. It was unclear whether the alpha- and beta-tubulin tails
      contribute equally to VDAC blockade and what effects might be due to sequence
      variations in these tail peptides or to tubulin post-translational modifications,
      which mostly occur on the tails. The nature of the contribution of the tubulin
      body beyond acting as an anchor for the tails had not been clarified either. Here
      we present peptide-protein chimeras to address these questions. These constructs
      allow us to easily combine a tail peptide with different proteins or combine
      different tail peptides with a particular protein. The results show that a single
      tail grafted to an inert protein is sufficient to produce channel closure similar
      to that observed with tubulin. We show that the beta-tail is more than an order
      of magnitude more potent than the alpha-tail and that the lower alpha-tail
      activity is largely due to the presence of a terminal tyrosine. Detyrosination
      activates the alpha-tail, and activation is reversed by the removal of the
      glutamic acid penultimate to the tyrosine. Nitration of tyrosine reverses the
      tyrosine inhibition of binding and even induces prolonged VDAC closures. Our
      results demonstrate that small changes in sequence or post-translational
      modification of the unstructured tails of tubulin result in substantial changes
      in VDAC closure. 

PMID- 26306045
TI  - Hsp31 Is a Stress Response Chaperone That Intervenes in the Protein Misfolding
      Process.
AB  - The Saccharomyces cerevisiae heat shock protein Hsp31 is a stress-inducible
      homodimeric protein that is involved in diauxic shift reprogramming and has
      glyoxalase activity. We show that substoichiometric concentrations of Hsp31 can
      abrogate aggregation of a broad array of substrates in vitro. Hsp31 also
      modulates the aggregation of alpha-synuclein (alphaSyn), a target of the
      chaperone activity of human DJ-1, an Hsp31 homolog. We demonstrate that Hsp31 is
      able to suppress the in vitro fibrillization or aggregation of alphaSyn, citrate
      synthase and insulin. Chaperone activity was also observed in vivo because
      constitutive overexpression of Hsp31 reduced the incidence of alphaSyn
      cytoplasmic foci, and yeast cells were rescued from alphaSyn-generated
      proteotoxicity upon Hsp31 overexpression. Moreover, we showed that Hsp31 protein
      levels are increased by H2O2, in the diauxic phase of normal growth conditions,
      and in cells under alphaSyn-mediated proteotoxic stress. We show that Hsp31
      chaperone activity and not the methylglyoxalase activity or the autophagy pathway
      drives the protective effects. We also demonstrate reduced aggregation of the
      Sup35 prion domain, PrD-Sup35, as visualized by fluorescent protein fusions. In
      addition, Hsp31 acts on its substrates prior to the formation of large aggregates
      because Hsp31 does not mutually localize with prion aggregates, and it prevents
      the formation of detectable in vitro alphaSyn fibrils. These studies establish
      that the protective role of Hsp31 against cellular stress is achieved by
      chaperone activity that intervenes early in the protein misfolding process and is
      effective on a wide spectrum of substrate proteins, including alphaSyn and prion
      proteins.

PMID- 26306049
TI  - Disability Insurance and the Great Recession.

PMID- 26306047
TI  - Modulation of wound healing and scar formation by MG53 protein-mediated cell
      membrane repair.
AB  - Cell membrane repair is an important aspect of physiology, and disruption of this
      process can result in pathophysiology in a number of different tissues, including
      wound healing, chronic ulcer and scarring. We have previously identified a novel
      tripartite motif family protein, MG53, as an essential component of the cell
      membrane repair machinery. Here we report the functional role of MG53 in the
      modulation of wound healing and scarring. Although MG53 is absent from
      keratinocytes and fibroblasts, remarkable defects in skin architecture and
      collagen overproduction are observed in mg53(-/-) mice, and these animals display
      delayed wound healing and abnormal scarring. Recombinant human MG53 (rhMG53)
      protein, encapsulated in a hydrogel formulation, facilitates wound healing and
      prevents scarring in rodent models of dermal injuries. An in vitro study shows
      that rhMG53 protects against acute injury to keratinocytes and facilitates the
      migration of fibroblasts in response to scratch wounding. During fibrotic
      remodeling, rhMG53 interferes with TGF-beta-dependent activation of myofibroblast
      differentiation. The resulting down-regulation of alpha smooth muscle actin and
      extracellular matrix proteins contributes to reduced scarring. Overall, these
      studies establish a trifunctional role for MG53 as a facilitator of rapid injury
      repair, a mediator of cell migration, and a modulator of myofibroblast
      differentiation during wound healing. Targeting the functional interaction
      between MG53 and TGF-beta signaling may present a potentially effective means for
      promoting scarless wound healing. 

PMID- 26306048
TI  - Fyn Activation of mTORC1 Stimulates the IRE1alpha-JNK Pathway, Leading to Cell
      Death.
AB  - We previously reported that the skeletal muscle-specific overexpression of Fyn in
      mice resulted in a severe muscle wasting phenotype despite the activation of
      mTORC1 signaling. To investigate the bases for the loss of muscle fiber mass, we
      examined the relationship between Fyn activation of mTORC1, JNK, and endoplasmic
      reticulum stress. Overexpression of Fyn in skeletal muscle in vivo and in HEK293T
      cells in culture resulted in the activation of IRE1alpha and JNK, leading to
      increased cell death. Fyn synergized with the general endoplasmic reticulum
      stress inducer thapsigargin, resulting in the activation of IRE1alpha and further
      accelerated cell death. Moreover, inhibition of mTORC1 with rapamycin suppressed
      IRE1alpha activation and JNK phosphorylation, resulting in protecting cells
      against Fyn- and thapsigargin-induced cell death. Moreover, rapamycin treatment
      in vivo reduced the skeletal muscle IRE1alpha activation in the Fyn
      overexpressing transgenic mice. Together, these data demonstrate the presence of
      a Fyn-induced endoplasmic reticulum stress that occurred, at least in part,
      through the activation of mTORC1, as well as subsequent activation of the
      IRE1alpha-JNK pathway driving cell death.

PMID- 26306050
TI  - DEVELOPMENTAL PALEOBIOLOGY OF THE VERTEBRATE SKELETON.
AB  - Studies of the development of organisms can reveal crucial information on
      homology of structures. Developmental data are not peculiar to living organisms,
      and they are routinely preserved in the mineralized tissues that comprise the
      vertebrate skeleton, allowing us to obtain direct insight into the developmental
      evolution of this most formative of vertebrate innovations. The pattern of
      developmental processes is recorded in fossils as successive stages inferred from
      the gross morphology of multiple specimens and, more reliably and routinely,
      through the ontogenetic stages of development seen in the skeletal histology of
      individuals. Traditional techniques are destructive and restricted to a 2-D plane
      with the third dimension inferred. Effective non-invasive methods of visualizing
      paleohistology to reconstruct developmental stages of the skeleton are necessary.
      In a brief survey of paleohistological techniques we discuss the pros and cons of
      these methods. The use of tomographic methods to reconstruct development of
      organs is exemplified by the study of the placoderm dentition. Testing evidence
      for the presence of teeth in placoderms, the first jawed vertebrates, we compare
      the methods that have been used. These include inferring the development from
      morphology, and using serial sectioning, microCT or synchrotron X-ray tomographic
      microscopy (SRXTM) to reconstruct growth stages and directions of growth. The
      ensuing developmental interpretations are biased by the methods and degree of
      inference. The most direct and reliable method is using SRXTM data to trace
      sclerochronology. The resulting developmental data can be used to resolve
      homology and test hypotheses on the origin of evolutionary novelties.

PMID- 26306051
TI  - BEYOND THE PRINT-VIRTUAL PALEONTOLOGY IN SCIENCE PUBLISHING, OUTREACH, AND
      EDUCATION.
AB  - Virtual paleontology unites a variety of computational techniques and methods for
      the visualization and analysis of fossils. Due to their great potential and
      increasing availability, these methods have become immensely popular in the last
      decade. However, communicating the wealth of digital information and results
      produced by the various techniques is still exacerbated by traditional methods of
      publication. Transferring and processing three-dimensional information, such as
      interactive models or animations, into scientific publications still poses a
      challenge. Here, we present different methods and applications to communicate
      digital data in academia, outreach and education. Three-dimensional PDFs, QR
      codes, anaglyph stereo imaging, and rapid prototyping-methods routinely used in
      the engineering, entertainment, or medical industries-are outlined and evaluated
      for their potential in science publishing and public engagement. Although
      limitations remain, these are simple, mostly cost-effective, and powerful tools
      to create novel and innovative resources for education, public engagement, or
      outreach.

PMID- 26306052
TI  - Tube bundle system: for monitoring of coal mine atmosphere.
AB  - A tube bundle system (TBS) is a mechanical system for continuously drawing gas
      samples through tubes from multiple monitoring points located in an underground
      coal mine. The gas samples are drawn via vacuum pump to the surface and are
      typically analyzed for oxygen, methane, carbon dioxide and carbon monoxide.
      Results of the gas analyses are displayed and recorded for further analysis.
      Trends in the composition of the mine atmosphere, such as increasing methane or
      carbon monoxide concentration, can be detected early, permitting rapid
      intervention that prevents problems, such as a potentially explosive atmosphere
      behind seals, fire or spontaneous combustion. TBS is a well-developed technology
      and has been used in coal mines around the world for more than 50 years. Most
      longwall coal mines in Australia deploy a TBS, usually with 30 to 40 monitoring
      points as part of their atmospheric monitoring. The primary uses of a TBS are
      detecting spontaneous combustion and maintaining sealed areas inert. The TBS
      might also provide mine atmosphere gas composition data after a catastrophe
      occurs in an underground mine, if the sampling tubes are not damaged. TBSs are
      not an alternative to statutory gas and ventilation airflow monitoring by
      electronic sensors or people; rather, they are an option to consider in an
      overall mine atmosphere monitoring strategy. This paper describes the hardware,
      software and operation of a TBS and presents one example of typical data from a
      longwall coal mine.

PMID- 26306053
TI  - How Has Educational Expansion Shaped Social Mobility Trends in the United States?
AB  - This contribution provides a long-term assessment of intergenerational social
      mobility trends in the United States across the 20th and early 21st century and
      assesses the determinants of those trends. In particular, we study how
      educational expansion has contributed to the observed changes in mobility
      opportunities for men across cohorts. Drawing on recently developed decomposition
      methods, we empirically identify the contribution of each of the multiple
      channels through which changing rates of educational participation shape mobility
      trends. We find that a modest but gradual increase in social class mobility can
      nearly exclusively be ascribed to an interaction known as the compositional
      effect, according to which the direct influence of social class backgrounds on
      social class destinations is lower among the growing number of individuals
      attaining higher levels of education. This dominant role of the compositional
      effect is also due to the fact that, despite pronounced changes in the
      distribution of education, class inequality in education has remained stable
      while class returns to education have shown no consistent trend. Our analyses
      also provide a cautionary tale about mistaking increasing levels of social class
      mobility for a general trend towards more fluidity in the United States. The
      impact of parental education on son's educational and class attainment has grown
      or remained stable, respectively. Here, the compositional effect pertaining to
      the direct association between parental education and son's class attainment
      counteracts a long-term trend of increasing inequality in educational attainment
      tied to parents' education.

PMID- 26306054
TI  - Development of the Japanese National Disaster Medical System and Experiences
      during the Great East Japan Earthquake.
AB  - After the Great Hanshin-Awaji Earthquake in 1995, the Japanese national disaster
      medical system (NDMS) was developed. It mainly consists of four components,
      namely, a disaster base hospital, an emergency medical information system, a
      disaster medical assistance team (DMAT), and national aeromedical evacuation
      (AE). The NDMS was tested for the first time in a real disaster situation during
      the Great East Japan Earthquake in 2011. Two airports and one base were appointed
      as DMAT gathering places, and approximately 393 DMAT members divided into 78
      teams were transported by Japan Air Self-Defense Force (JASDF) aircrafts to two
      AE staging bases the following day. Staging care units were installed at Hanamaki
      Airport, Fukushima Airport, and the Japan Ground Self-Defense Force Camp
      Kasuminome, and 69, 14 and 24 DMAT teams were placed at those locations,
      respectively. In total, 19 patients were evacuated using JASDF fixed-wing
      aircraft. Important issues requiring attention became clear through the
      experiences of the Great East Japan Earthquake and will be discussed in this
      paper. 

PMID- 26306056
TI  - The Skills of Facilitator Nurses in Psycho-Social Group Intervention for Cancer
      Patients.
AB  - BACKGROUND: The objective of this study was to provide cancer patients with a
      psychosocial group intervention consisting of 3 parts, i.e., education on how to
      cope with stress and solve problems, group discussions, and progressive muscle
      relaxation, and to investigate the intervention techniques of Japanese
      facilitators. METHODS: Group interventions for breast cancer patients performed
      by 3 facilitators were analyzed qualitatively and inductively using a
      phenomenological approach. RESULTS: The skills of facilitators included 10
      intervention techniques and 1 problem in interventions. Intervention techniques,
      which promote group dynamics and thereby help participants acquire improvements
      in their coping abilities and quality of life (QOL), were somewhat different
      between new and experienced facilitators, with the content showing immaturity and
      maturity in the new and experienced facilitators, respectively. Both experienced
      and new facilitators faced the risk of experiencing problems in interventions,
      which countered the purpose of the intervention of improving the participants'
      coping abilities or QOL. CONCLUSION: While intervention skills are necessary for
      facilitators to execute group interventions, it must be borne in mind, that even
      well-experienced facilitators may not always be able to accomplish skillful
      intervention.

PMID- 26306055
TI  - Influence of Olmesartan on Sirtuin 1 mRNA Expression in 5/6 Nephrectomized
      Spontaneously Hypertensive Rats.
AB  - BACKGROUND: Recent studies revealed that sirtuin 1 (SIRT1) has a relation to the
      mechanism of transforming growth factor-beta (TGF-beta) mediated apoptosis in
      glomerular mesangial cells and plays an important role in blood pressure
      regulation. It has been suggested that SIRT1 contributes to the renoprotective
      effect of angiotensin receptor blocker (ARB), but this has not yet become clearly
      recognized. In this study, we examined the relationship between SIRT1 and the
      therapeutic effect of olmesartan on renal injury in nephrectomized spontaneously
      hypertensive rats (SHRs). METHODS: Male Wistar rats and 5/6 nephrectomized
      (5/6Nx) SHRs were assigned to 5 groups as follows: group A, Wistar rats; group B,
      Wistar rats administered high-dose olmesartan (15 mg/kg/day); group C, 5/6Nx
      SHRs; group D, 5/6Nx SHRs administered low-dose (3 mg/kg/day) olmesartan; and
      group E, 5/6Nx SHRs administered high-dose olmesartan. The drugs were
      administered for 12 weeks. Blood pressure and urinary protein excretion were
      measured every 4 weeks. Serum creatinine, glomerular sclerosis, SIRT1 mRNA level,
      TGF-beta mRNA level and klotho mRNA level were measured at the end of the
      examination. RESULTS: Systolic blood pressure, urinary protein excretion, serum
      creatinine and glomerular sclerosis in Wistar rats were significantly lower than
      that of 5/6Nx SHRs. Among 5/6Nx SHRs, high doses of olmesartan significantly
      decreased urinary protein excretion, serum creatinine and glomerular sclerosis
      compared to the non-treated and low-dose olmesartan groups. Expression of SIRT1
      and klotho mRNA were significantly downregulated in 5/6Nx SHRs; however,
      olmesartan did not attribute to any change in gene expression. Expression of TGF
      beta mRNA was significantly increased in 5/6Nx SHRs, and olmesartan did not
      affect the level of TGF-beta mRNA expression. CONCLUSION: Expression of SIRT1 is
      decreased in 5/6Nx SHRs compared to Wistar rats. Olmesartan suppressed glomerular
      sclerosis, but did not increase the expression of SIRT1, suggesting that the
      renoprotective effect of olmesartan is independent of the SIRT1 pathway.

PMID- 26306057
TI  - Changes in Standard Treatments and Postoperative Outcomes for Advanced Gastric
      Cancer at One Institute over an 11-Year Period.
AB  - BACKGROUND: Reportedly, the recently established postoperative adjuvant
      chemotherapies (ADJs) with tegafur and uracil (UFT) or fluoropyrimidine S (S-1)
      show better survival than surgery alone in patients with advanced gastric cancer
      (GC). We analyzed chronological changes in postoperative prognosis of patients
      with advanced GC in our institute, and investigated the efficacy of ADJ in
      patients with stage II-III GC. METHODS: Of 143 patients with stage II-III GC who
      underwent curative gastrectomy at Tottori University Hospital between 1998 and
      2008, three died with operative complications within 1 month after surgery. The
      remaining 140 patients were followed to the end of 2013. We compared disease-free
      survival (DFS) and clinicopathological differences between 82 patients who
      underwent gastrectomy during 1998-2002 (Group A) and 58 patients who underwent
      gastrectomy during 2003-2008 (Group B). RESULTS: Operative quality, as
      represented by number of dissected lymph nodes, was similar in both groups, but
      the recurrence rate of Group A (51.2%) was higher than in Group B (37.9%, P =
      0.12) and the 5-year DFS rate of Group B (62.3%) was higher than that of Group A
      (50.2%, P = 0.095). In stage II, the 5-year DFS rate of patients in Group B
      (73.3%) was similar to Group A (77%), but at tumor stage III, the 5-year DFS rate
      of patients in Group B increased to 48.7%, compared with 33.1% of Group A.
      Between 2003 and 2008, S-1 was widely used as ADJ for stage II-III GC.
      CONCLUSION: Postoperative ADJ with S-1 improved DFS of patients with stage III
      gastric cancer.

PMID- 26306058
TI  - Psychological Characteristics in Patients during Treatment for Tobacco
      Dependence.
AB  - BACKGROUND: Few studies compare mood in tobacco cessation patients with mood in
      continuing smokers and then estimate the effects of a tobacco cessation program
      according to status of mood. We investigated whether mood in patients (n = 7)
      dependent on tobacco improved through the standard Japanese 12-week program for
      smoking cessation comparing smokers (n = 11) and nonsmokers (n = 16). METHODS: A
      brief Japanese version of the short profile of mood states (POMS) was used in
      this study. The subscale includes 5 negative mood factors (tension-anxiety,
      depression, anger-hostility, fatigue and confusion-bewilderment) and positive
      mood factors (vigor-activity). We also examined expiratory CO concentration
      (ppm), percentage of COHb, urinary nicotine and its metabolite concentration,
      Brinkman index, and tobacco dependence score (TDS) for both smoking cessation
      group and smokers group. RESULTS: All the short profiles for mood state points in
      nonsmokers were below 50. Two of TDS items in smoking cessation patients were
      significantly higher in percentage than those in smokers. Brinkman indices and
      expiratory CO concentration were significantly higher in smoking cessation
      patients than those in smokers. The rate of improvement in tension-anxiety points
      in smoking cessation patients was significantly higher than that in smokers.
      CONCLUSION: Counseling according to the standard program in the treatment of
      tobacco dependence may be an effective procedure to improve mood status.

PMID- 26306059
TI  - Microcalcification of Tumor is a Predictor of Response to Neoadjuvant
      Chemotherapy for Invasive Breast Carcinoma.
AB  - BACKGROUND: In recent years, neoadjuvant chemotherapy (NAC) is often performed
      for patients with unresectable breast carcinoma or without indication of breast
      conserving therapy. However, it is currently difficult to predict response to NAC
      with diagnostic imaging of breast carcinoma. In this study, we investigated
      imaging findings that could serve as a predictor of the response to NAC for
      patients with invasive breast carcinoma. METHODS: Twenty-six patients with
      invasive breast carcinoma who received NAC at the Division of Breast and
      Endocrine Surgery of Tottori University Hospital between January 2010 and May
      2014 were retrospectively investigated. Their imaging findings from mammograms
      and ultrasonograms were reviewed. The association between findings on mammograms
      and ultrasonograms captured before NAC and response to treatment after NAC was
      examined. RESULTS: Of the 26 patients with invasive breast carcinoma, 19 (73%)
      responded well to treatment and 7 (27%) did not. Most notably, all 10 patients
      who had microcalcifications on mammogram responded well to treatment (53% of
      responders), and all patients who did not respond to treatment had no
      microcalcifications (P < 0.05). Of these 10 patients, 9 (90%) had
      microcalcifications of comedo type and one (10%) had non comedo type. As a
      distribution, 8 of the 10 (80%) had a clustered type of microcalcifications and
      the remaining 2 (20%) had a segmental type of them. CONCLUSION:
      Microcalcifications of tumor observed in mammogram (particularly comedo type)
      could be a predictor of response to NAC for patients with invasive breast
      carcinoma.

PMID- 26306061
TI  - Children's Physic: Medical Perceptions and Treatment of Sick Children in Early
      Modern England, c. 1580-1720.
AB  - Historians of medicine, childhood and paediatrics have often assumed that early
      modern doctors neither treated children, nor adapted their medicines to suit the
      peculiar temperaments of the young. Through an examination of medical textbooks
      and doctors' casebooks, this article refutes these assumptions. It argues that
      medical authors and practising doctors regularly treated children, and were
      careful to tailor their remedies to complement the distinctive constitutions of
      children. Thus, this article proposes that a concept of 'children's physic'
      existed in early modern England. This term refers to the notion that children
      were physiologically distinct, requiring special medical care. Children's physic
      was rooted in the ancient traditions of Hippocratic and Galenic medicine: it was
      the child's humoral make-up that underpinned all medical ideas about children's
      bodies, minds, diseases and treatments. Children abounded in the humour blood,
      which made them humid and weak, and in need of medicines of a particularly gentle
      nature.

PMID- 26306060
TI  - Clinical Significance of Microcalcifications Detection in Invasive Breast
      Carcinoma.
AB  - BACKGROUND: Recently, a lot of cases with microcalcifications of the breast are
      pointed by the images of mammography (MG), because breast screening using MG
      become common. Although MG is a gold standard modality for detecting
      microcalcifications, images of ultrasonography (US) are now feasible to detect
      microcalcifications with recent improvements to ultrasound diagnostic devices. In
      this report, we analyzed clinical significance of microcalcifications detected
      with US images in invasive breast carcinoma. METHODS: Eighty-eight patients with
      invasive breast carcinoma who underwent MG and US before surgery at the Division
      of Breast and Endocrine Surgery of Tottori University Hospital between January
      2012 and August 2013. After reviewing US images, the association between the
      presence of echogenic spots that indicate microcalcifications and images of MG or
      pathological findings was assessed. RESULTS: Patients without microcalcifications
      on US images were significantly more likely to have the Luminal A subtype and a
      lower nuclear grading. Conversely, patients with microcalcifications on US images
      were significantly more likely to have higher level of MIB-1 index,
      lymphovascular invasion, comedonecrosis and lymph node metastasis. The rate of
      detecting microcalcifications on US images was relatively good, with 81.8% of
      sensitivity, 94.5% of specificity and 89.8% of diagnostic accuracy. Among the
      calcifications detected by MG images, detected rate of calcifications with US
      images was higher in necrotic type (92.6%) than secretory type (33.3%).
      CONCLUSION: This study suggest that microcalcifications of tumors detected by US
      images could serve as an useful prediction to evaluate the degree of malignancy
      for patients with invasive breast carcinoma.

PMID- 26306062
TI  - From the Editor-in-Chief's Desk.

PMID- 26306063
TI  - Risk Factors, Pattern and Clinical Outcome of Acute Graft Versus Host Disease in
      Acute Leukemia Patients Undergoing Allogeneic Stem Cell Transplant.
AB  - We sought to determine risk factors, pattern and outcome of acute graft versus
      host disease (aGVHD) in seventy-seven acute leukemia patients who underwent
      allogeneic stem cell transplant at our centre from January 2008 to March 2013.
      GVHD prophylaxis with cyclosporine-methotrexate or cyclosporine-mycophenolate
      mofetil was used. Patients were divided in 2 groups, grade II-IV aGVHD (group A)
      and grade 0-I aGVHD (group B). Incidence of any grade and grade II-IV aGVHD was
      44 and 18 %, respectively. The most common site of aGVHD was gastro-intestinal
      tract (65 %) followed by skin (35 %). Higher total nucleated cell (TNC) dose
      infused was associated with increased incidence of grade II-IV aGVHD. Incidence
      of relapse and incidence of slippage of chimerism was 21 and 36 % in group A
      while 37 and 27 % in group B respectively. Transplant related mortality (TRM) was
      21 % in group A and 13 % in group B. Probability of OS and RFS at 4 years was 63
      and 34 % in group A compared with 40 and 38 % in group B, respectively. We
      conclude that higher TNC dose infused is a risk factor for grade II-IV aGVHD with
      gut being the commonest site. Grade II-IV aGVHD did not have a significant impact
      on incidence of relapse, TRM and OS. 

PMID- 26306064
TI  - Safety and Efficacy of Eltrombopag in Post-hematopoietic Stem Cell
      Transplantation (HSCT) Thrombocytopenia.
AB  - Twelve adult patients (median age 29.5 years) were started on Eltrombopag 25-50
      mg/day for post-hematopoietic stem cell transplantation (HSCT) thrombocytopenia.
      All patients were having primary thrombocytopenia after HSCT. No patient had
      other secondary cause for thrombocytopenia. Two patients were allogenic subsets
      (1 acute myeloid leukemia i.e., AML and 1 aplastic anemia), and 10 were
      autologous transplants (3 multiple myeloma, 6 lymphoma and 1 AML). Nine patients
      were males, three were females. The median time of starting Eltrombopag was 21
      days post-stem cell infusion (range day +17 to +60) at a median platelet count of
      9,000/cmm (range 3,000-11,000/cmm). The median duration for treatment was 29
      days. Median total dose of 812.5 mg was received by patients and they had a
      median platelet increment of 36,000/cmm. We observed that there were no adverse
      effects in these patients and there was a gradual increase in platelet count so
      that none of the patients had any complication due to thrombocytopenia. The cost
      of treatment was less than the cost of extended hospitalization and irradiated
      single donor platelet transfusion. 

PMID- 26306065
TI  - MicroRNA Expression Analysis in Patients with Primary Myelofibrosis, Polycythemia
      vera and Essential Thrombocythemia.
AB  - MicroRNAs (miRNA) are small non-coding RNA molecules that play critical roles in
      cell differentiation, proliferation and apoptosis and thus regulate
      haematopoietic stem cells and committed progenitor cells. We analyzed expressions
      of miRNAs associated with hematopoietic transformation of myeloid, erythroid and
      megakaryocytic progenitor cells during haematopoiesis (mir155, mir181a, mir221,
      mir222, mir223, mir451), in patients with primary myelofibrosis (PMF) (n = 22),
      polycythemia vera (PV) (n = 33), essential thrombocythemia (ET) (n = 49) and in
      healthy controls (n = 40) by quantitate/real time polymerase chain reaction. RT
      PCR testing was negative for BCR-ABL1 fusion gene in all the patients. Mir155 was
      expressed in higher levels in all 3 disorders (p < 0.05). Mir221 was higher
      especially in ET and PMF group (p < 0.05). Mir222 expression was lower in PV
      patients (p < 0.05) and higher in ET and PMF patients compared to control group.
      Mir223 expression was higher in ET and PMF group than control group (p > 0.05).
      Mir451 levels were lower in all three groups compared to control group (p <
      0.05). There was no difference in expression levels of mir181a between groups.
      JAK2V617F positivity, co-morbidities, drugs, and gender did not affect miRNA
      expressions. This study holds promise for the future application of these
      molecules for differential diagnosis and as therapeutic targets in Philadelphia
      chromosome negative myeloproliferative neoplasms. 

PMID- 26306066
TI  - Allogeneic Hematopoietic Stem Cell Transplantation: A Salvage Treatment for
      Relapsed or Refractory Lymphoma.
AB  - To analyze the efficacy and safety of allogeneic hematopoietic stem cell
      transplantation (Allo-HSCT) in patients with relapsed or refractory lymphoma, the
      therapeutic efficacy, safety, and survival of 23 patients were evaluated. There
      were 18 (78.3 %) patients with relapsed lymphoma and 5 (21.7 %) patients with
      refractory lymphoma. Patients were grafted from human leukocyte antigen (HLA)
      matched (10) or mismatched (7) related donors, or matched unrelated donors (6).
      The responses after Allo-HSCT included 13 (56.5 %) cases of complete remission, 5
      (21.7 %) cases of partial remission, and 5 (21.7 %) cases of progressive disease.
      Overall, 16 of 23 patients were alive at a median follow up of 1,035 days (range
      60-2,613), five patients died because of non-relapsed mortality, and two patients
      died of progressive disease. Progression-free survival rates were 64.6 and 48.4 %
      at 12 and 24 months, respectively, and overall survival rates were 68.6 and 59.5
      % at 12 and 24 months, respectively. Allo-HSCT may be a salvage treatment for
      relapsed or refractory lymphoma. Myeloablative conditioning regimens may be
      effective and safe. 

PMID- 26306067
TI  - Alginate Dressing Application in Hemostasis After Using Seldinger Peripherally
      Inserted Central Venous Catheter in Tumor Patients.
AB  - The aim of this study is to observe hemostatic effects of alginate dressing after
      using seldinger PICC catheter in tumor patients. Sixty tumor patients with PICC
      receiving chemotherapy were divided into the test group (30 cases) and the
      control group (30 cases) randomly. The test group was treated with alginate
      dressing and oppressed by the puncture point, while the control group was treated
      with gauze of the same size. PICC transparent films were used in both groups.
      Finally, dressing ooze blood soaked states on the puncture points and dressing
      change times were observed in the two groups for 1 week. Moreover, local
      infection rate and incidence of catheter leak were also evaluated. The results
      showed that the oozing of blood and the changing frequency in the test group were
      obviously less than that in the control group, and there has a statistical
      difference (P < 0.05). Infection rate of puncture point and incidence of catheter
      leak were simultaneously reduced in the test group. Alginate dressing is
      effective in preventing seldinger PICC catheter-induced hemorrhage. 

PMID- 26306068
TI  - Pattern of Venous Thrombosis in Cancer Patients: Frequency and Survival Effect;
      Single Center Experience.
AB  - Venous thromboembolism (VTE) represents one of the most important causes of
      morbidity and mortality in cancer patients. This investigation was undertaken to
      investigate the natural history of VTE in the oncology center in a tertiary care
      hospital. We did a retrospective study on cancer patients who presented to King
      Abdullah Medical city in Holly capital; a tertiary care hospital; from May 2011
      to June 2013. Follow up period was calculated from time of VTE diagnosis till the
      last clinical visit or till patient death. Among 1,678 cancer patients, 132 (7.87
      %) were diagnosed with VTE. The median patient age was 53.5 years, with female to
      male ratio 1.3/1. Thirty one patients (23.5 %) were diagnosed with VTE and cancer
      simultaneously, seventy four patients (56.1 %) were on chemotherapy and twenty
      eight patients (21.2 %) were on best supportive care.VTE were symptomatic in 110
      patients (83.3 %) and asymptomatic in 22 patients (16.7 %). Lower limbs were the
      commonest site (42.4 %) with the highest incidence in patients with advanced
      stages (93 %). Forty nine (37 %) patients were receiving LMWH as prophylaxis.
      Median survival in months for patients with VTE prophylaxis versus without
      prophylactic, and asymptomatic versus symptomatic were (12.6 vs 6.3; p 0.12 and
      9.8 vs 12.4; p 0.885, respectively). There is underutilization of
      thromboprophylaxis in our region, which needs more effort to reduce VTE burden.
      Also we need large prospective studies to clarify the impact of VTE symptoms and
      presentation on patient's survival. 

PMID- 26306069
TI  - Does Profile of Hemoglobin Ebeta-thalassemia Patients Change After Splenectomy?
      Experience of a Tertiary Thalassemia Care Centre in Eastern India.
AB  - Hemoglobin Ebeta-thalassemia is by far the commonest form of thalassemia
      intermedia. Its phenotype ranges from mild anemia to severe transfusion
      dependency necessitating splenectomy in many patients. The present study aimed to
      systematically analyze both clinical as well as laboratory parameters in profile
      of Ebeta-thalassemia patients after splenectomy in terms of transfusion
      requirement, infections and other complications. Retrospective study conducted
      over a period of 3 years included 72 cases of splenectomized Ebeta-thalassaemia
      patients, considering decrease in transfusion requirements, new complications,
      antibiotic, anti-malarial prophylaxis and iron chelation therapy. Out of 1380
      registered Ebeta-thalassemia patients, 618 (44.78 %) were regularly transfused
      and 72(5.22 %) underwent splenectomy. Mean age of diagnosis was 10.3 years.
      Nineteen patients (26.4 %) underwent splenectomy between 5 and 10 years, 38 cases
      (52.7 %) between 10 and 20 years. The leading cause (51.39 %) for splenectomy was
      mechanical discomfort. Mean steady state hemoglobin raised from pre-splenectomy
      level of 5.43-6.8 gm/dl after splenectomy. Mean transfusion requirement reduced
      from 18.1 to 7.8 units/year. Mean serum ferritin level increased from 907.58 to
      1,091.6 ng/ml. Post-splenectomy; 21 (29.17 %) patients developed facial
      deformities, 17 (23.6 %) delayed pubertal growth, 11 (15.28 %) venous
      thromboembolism, five (6.94 %) pulmonary hypertension and four (5.5 %) had
      extramedullary hematopoiesis. Five (6.96 %) patients had documented bacterial
      infections and two (2.78 %) suffered from malaria. Forty eight patients (66.67 %)
      started with iron chelation therapy; but majority (52.7 %) stopped. Major
      advantage of splenectomy is reduced transfusion requirement, though it cannot
      prevent skeletal abnormalities and delayed pubertal growth. In resource
      constraint countries like India, routine anti-malarial and antibacterial
      prophylaxis is not desirable; iron chelation therapy should be encouraged and
      ensured. 

PMID- 26306070
TI  - A Comparative Assessment of Quality of Platelet Concentrates Prepared by Buffy
      Coat Poor Platelet Concentrate Method and Apheresis Derived Platelet Concentrate
      Method.
AB  - Many blood centres in country don't have costly apheresis technology and rely
      heavily on the platelet production from whole blood donation. We conducted this
      study with the aim to compare the quality of platelet concentrates (PC) prepared
      by Buffy Coat derived (BC-PC) and apheresis derived platelet concentrate
      (Apheresis-PC). Our objective was to collect data by analysis of platelet
      concentrates prepared by BC-PC methods and Apheresis-PC methods in respect of
      swirling, volume, platelet count, WBC count and pH of the PC units and elaborate
      on the quality parameters. Tertiary Care Hospital and Medical College. We
      assessed a total of 200 BC-PC and 200 Apheresis-PC for their in vitro quality by
      observing swirling, volume of PC, platelet count/unit, WBC count/unit and pH, to
      see if they satisfy the recommended quality criteria. Data was analyzed using
      appropriate statistical technique under the guidance of biostatistician.
      Apheresis-PC units showed better swirling than BC-PC units (Chi square test; P <
      0.05). There was a significant difference in proportion of units satisfying the
      required volume QC between the two methods (Chi-square test; P < 0.05). Apheresis
      PC showed better adherence to the physiological pH values (Student's unpaired t
      test; P < 0.05). The units of BC-PC and Apheresis-PC did not show significant
      difference in proportion of units satisfying the Platelet count per unit and
      residual WBC count per count (Chi square; P 0.203 and 0.617 respectively). There
      was comparable adherence to QC requirement for platelet count and WBC
      contamination in two methods. BC-PC were found to be adhering lesser to QC
      parameters for swirling, volume and pH, but found to be in required QC limits.
      BCPC can be used effectively in the majority of thrombocytopenic patients in
      resource poor setting. 

PMID- 26306071
TI  - Hypereosinophilia in Acute Lymphoblastic Leukemia: Two Cases with Review of
      Literature.
AB  - Eosinophilia is rare in acute leukemia at presentation. Discrete reports and case
      studies in recent years have created significant interest in the field of "Acute
      leukemia with eosinophilia". We herein present two cases of eosinophilia in
      association with acute lymphoblastic leukemia with brief review of literature in
      this field. First case is about 21-year-old female who presented with mediastinal
      mass along with leukocytosis and hypereosinophilia. On evaluation, she was found
      to have T cell acute lymphoblastic leukemia. After ruling out benign causes of
      eosinophilia, she was treated with modified BFM-90 protocol. Her eosinophilia
      resolved after 4 weeks of induction therapy. Second case is about 32-year-old
      male who was diagnosed as a case of mixed phenotype leukemia (B cell/myeloid
      type) along with severe eosinophilia. His hypereosinophilia finally resolved by
      week 16 of modified BFM-90 protocol. Diagnosing ALL is challenging when
      eosinophilia is the initial presentation. These two cases emphasize on the
      importance of considering ALL amongst one of the etiological causes of
      eosinophilia as delay in diagnosis endangers patient's life at risk. Also
      eosinophilia per se is an independent poor risk factor, hence prompt diagnosis
      and early treatment is the key in all such cases. 

PMID- 26306072
TI  - Myeloid Sarcoma: An Unusual Case of Mediastinal Mass and Malignant Pleural
      Effusion with Review of Literature.
AB  - Myeloid sarcoma is an extramedullary tumor seen most commonly in patients with
      acute myeloid leukemia and less frequently in chronic myeloid leukemia,
      myelodysplastic syndrome and rarely, in an isolated form without any other
      underlying malignancy. Malignant pleural effusion in hematological malignancies
      is rare when compared with solid tumors. We present an unusual case of myeloid
      sarcoma in which a mediastinal mass with pleural effusion was the initial
      presentation. A 27 year old gentleman presented with complaints of fever, chest
      pain and swelling in the anterior chest wall for 6 months. Examination revealed a
      lump measuring 5 * 5 cm on the left side of the chest wall. Hematological
      evaluation showed hemoglobin-14.2 g/dL, platelet count-233 * 10(9)/L, TLC-117 *
      10(6)/L with normal differential counts. Contrast enhanced computerised
      tomography (CECT) confirmed the presence of a soft tissue mass in the superior
      mediastinum abutting against the chest wall. Core biopsy was suggestive of
      myeloid sarcoma and immunohistochemistry was positive for myeloperoxidase and
      negative for CD3, CD 20 and CD 23. Pleural fluid analysis showed the presence of
      malignant cells. Bone marrow examination did not show an excess of blasts. A
      final diagnosis of extramedullary myeloid sarcoma with malignant pleural effusion
      was made. The patient was given induction chemotherapy (3 + 7 regimen) with
      daunorubicin and cytosine arabinoside. Repeat CECT done on day 28 showed complete
      resolution of pleural effusion and significant reduction in the size of
      mediastinal mass. The patient has successfully completed three cycles of
      consolidation therapy following which there has been complete resolution of the
      mass. He remains asymptomatic on close follow up. 

PMID- 26306073
TI  - IgG Lambda Myeloma Presenting as Plasmacytic Ascites: Case Report and Review of
      Literature.
AB  - Multiple myeloma is a neoplastic disease of plasma cells accounting for 13 % of
      haematological malignancies and 2 % of all malignancies worldwide. Ascites may
      develop very rarely during the course of disease in multiple myeloma. We report
      the case of a 78 years old male with IgG lambda multiple myeloma who initially
      presented with plasmacytic ascites. An exhaustive review of world literature
      reveals 65 cases of ascites to have been reported in myeloma over a span of 62
      years (1952 till date), usually developing in the course of treatment. This is
      the 7th case of plasmacytic ascites to have been diagnosed at initial
      presentation. We review the clinical features, diagnosis, prognostic significance
      and treatment of such cases. 

PMID- 26306075
TI  - Tube bundle system studies at Signal Peak Energy Bull Mountains #1 Mine.
AB  - A tube bundle system (TBS) is a mechanical system for continuously drawing gas
      samples through tubes from multiple monitoring points located in an underground
      coal mine for analysis and display on the surface. The U.S. National Institute
      for Occupational Safety and Health (NIOSH), in collaboration with Signal Peak
      Energy (SPE), LLC, Bull Mountains No. 1 Mine, operated a TBS during mining of two
      bleederless, longwall panels. This paper describes the gas analysis data and its
      interpretation. As verified by the TBS, coal at the SPE mine tends to oxidize
      slowly. It was known that a reservoir of low-oxygen concentration atmosphere
      developed about 610 m (2,000 ft) behind the longwall face. A bleederless
      ventilation system facilitates formation of an inert atmosphere in this longwall
      gob and decreases the likelihood of spontaneous combustion. Connections of the
      mine atmosphere to the surface through subsidence cracks could allow airflow into
      the longwall gob, revive coal oxidation and increase spontaneous combustion risk.
      The atmospheric composition of the sealed areas was homogeneous, except in the
      immediate vicinity of suspected ingassing points. The TBS verified that gases
      within the partially sealed, bleederless longwall gob expanded into the longwall
      tailgate area when barometric pressure decreased. The concentration of carbon
      dioxide in the back return airflow at the longwall tailgate was observed to
      increase by a factor of three and possibly up to 10 times the typical background
      concentration of 0.5 to 1.0%, depending on the size of the longwall gob and the
      magnitude of barometric pressure decrease. TBS have the inherent disadvantage of
      slow response time due to travel time of the gas samples and sequential gas
      analyses. A TBS or similar continuous monitoring system could be beneficial in
      detecting and providing warning of potentially hazardous gas concentrations, if
      the slow response time of the system is always understood.

PMID- 26306074
TI  - Child Vocabulary, Maternal Behavior, and Inhibitory Control Development Among
      Spanish-Speaking Children.
AB  - RESEARCH FINDINGS: The roles of child lexical diversity and maternal sensitivity
      in the development of young children's inhibitory control were examined in 100
      low-income Hispanic Spanish-speaking children. Child communication utterances at
      age 21/2 years were transcribed from 10-min mother-child interactions to quantify
      lexical diversity. Maternal behavior was rated independently from the
      interactions. Inhibitory control was measured with a battery of tasks at ages
      21/2 and 31/2. Greater maternal sensitivity was correlated with higher vocabulary
      at 21/2. Greater vocabulary predicted positive growth in child inhibitory control
      skills from ages 21/2 to 31/2 in multivariable regression models that controlled
      for maternal education, family income, the home environment, and mothering
      quality. PRACTICE OR POLICY: These findings suggest that supporting vocabulary
      development in low-income Spanish-speaking children is important for the
      development of inhibitory control skills, an important foundation for school
      readiness and academic success.

PMID- 26306076
TI  - Formation of Organic Molecular Nanocrystals under Soft Confinement.
AB  - Methods to produce nano-sized organic molecular crystals in thin films are of
      great interest in the pharmaceutical industry due to the potential benefit of
      increased solubility of poorly soluble drugs and the advantages of film-based
      dosage forms over traditional tablet/capsule-based dosage form. One method to
      directly form organic nanocrystals is by crystallization in confined environments
      where the overall crystallization volume is constrained. We report the use of a
      novel solution impregnation method to form nanocrystals in polymer matrices with
      various microstructures in order to study the structure of the confined
      nanocrystals and the role of soft confinement and polymer chemistry on the
      nucleation process of nano-sized crystals. The particle diameter correlates with
      the microstructure of the polymer matrices and the nucleation kinetics. In
      addition, by carefully choosing the experimental conditions and the polymer
      matrix, polymorph control of nanocrystals can be achieved. Solid-state nuclear
      magnetic resonance (ssNMR) was used to examine the local structure of
      nanocrystals inside the polymer matrices and crystal polymer interactions. This
      method may serve as a novel formulation method to obtain nanocrystals of poorly
      soluble active pharmaceutical ingredients (APIs) for pharmaceutical industry.

PMID- 26306077
TI  - Outcome Assessments in Clinical Trials of Cryptococcal Meningitis: Considerations
      on Use of Early Fungicidal Activity as a Potential Surrogate Endpoint for All
      Cause Mortality.
AB  - Cryptococcal meningitis (CM) is a common disease in resource-challenged settings,
      with a high mortality within weeks of disease onset. Mortality remains high with
      current treatments, so more effective interventions are needed to decrease
      mortality. There has been interest in using the outcome assessment of
      quantification of fungus from cerebrospinal fluid as a replacement (surrogate)
      endpoint for all-cause mortality (ACM) as a means of decreasing sample size in
      randomized clinical trials in CM. To evaluate a biomarker as a potential
      surrogate endpoint to replace ACM requires several steps. This paper discusses
      the issues of determining whether the context of a disease is one where a
      potential surrogate endpoint is rational, the types of outcome assessments that
      might qualify as potential surrogates, and the process for evaluation of the
      evidence that a chosen biomarker is a valid replacement for ACM in the given
      context of use. We then apply those principles to the context of randomized
      clinical trials of CM.

PMID- 26306078
TI  - Anh H. Nguyen, MD.

PMID- 26306079
TI  - Cosmetic Asian Blepharoplasty and Periorbital Surgery.

PMID- 26306080
TI  - The Evolution of Looks and Expectations of Asian Eyelid and Eye Appearance.
AB  - Since Mikamo developed the double blepharoplasty technique at the end of the 19th
      century, there has been significant developments in the idealized periorbital
      appearance of the Asian patient. Currently there are four potential vectors of
      change possible (upper, lower, medial, and lateral). South Korea is the only
      country that most often utilizes the change in all four vectors. There is
      additionally a stark contrast between Asia-based and Western-based approach to
      the Asian eyes. In Asia, outside of South Korea, many surgeries employ a combined
      vertical upward vector and a medial directional change, particularly for the
      young eyes. In Western-based approaches, Asian blepharoplasty remains at this
      time primarily an open incision, upward vector change. 

PMID- 26306081
TI  - Physical Evaluation of the Asian Blepharoplasty Patient.
AB  - In contrast with Caucasian blepharoplasty, which is usually done for rejuvenation
      purposes, eyelid surgery for Asians is mainly done for cosmetic reasons. Here the
      authors present preoperative evaluation methods of Asian eyelids to overcome
      anatomical variations and determine the right aesthetic options. Proper selection
      of the most suitable operative methods guarantees optimal surgical results. 

PMID- 26306082
TI  - The Asian Eyelid: Relevant Anatomy.
AB  - The eyelid of Asians has its own unique characteristics. If the surgeon does not
      acknowledge this, aesthetically pleasing results will seldom be achieved. Here
      the authors review and summarize important up-to-date anatomical and relevant
      clinical studies of the Asian upper eyelid, aiming to help surgeons thoroughly
      understand its unique features, including Asian eyelid morphology, anatomical
      details, and the mechanisms of upper eyelid crease formation. Hopefully, an in
      depth understanding of the Asian eyelid will aid surgeons to accomplish their
      work and lead to novel new techniques in this field. 

PMID- 26306083
TI  - Subclinical Ptosis Correction: Incision, Partial Incision, and Nonincision: The
      Formation of the Double Fold.
AB  - Surgery to create eyelid folds accounts for the highest percentage of surgeries
      in Asians and Koreans who receive the surgery on the upper eyelid 2 to 3 times
      during their lifetimes for functional or cosmetic reasons. Patients are generally
      satisfied with the results-the eyes becoming brighter and bigger via the
      improvement of pseudoptosis by fold creation. The recent trend is to seek the
      "perfect" eye: a vertically and horizontally big palpebral fissure with more than
      90% cornea showing. Surgery of the levator aponeurosis-Muller muscle complex is
      required to expose the cornea, except in those patients who inherently have good
      levator-Muller function. However, many complications occur during surgeries of
      the levator aponeurosis-Muller muscle complex, which increase the reoperation
      rate. Here, the authors briefly summarize recent experiences correcting
      subclinical ptosis using the nonincision, incision, and partial incision methods.

PMID- 26306084
TI  - Reconsideration of the Epicanthus: Evolution of the Eyelid and the Devolutional
      Concept of Asian Blepharoplasty.
AB  - Double eyelidplasty is the most frequent cosmetic procedure for Asians; however,
      the epicanthal fold has been a conundrum that has limited the cosmetic results of
      Asian blepharoplasty. To achieve satisfactory results in an Asian double
      eyelidplasty, the key is an understanding of the true nature of the epicanthus.
      We propose that the epicanthus developed in the eyelid's evolutionary process.
      Selective detachment and superomedial reposition of the preseptal portion of the
      upper orbicularis muscle can resolve the primary cause of epicanthal formation
      without functional impairment. The vertical skin shortage and resultant skin
      tension of the upper eyelid can be corrected by subcutaneous dissection and
      transverse advancement of skin flap. An epicanthoplasty is part of the core
      surgery for Asian double eyelidplasty, especially when forming a parallel type of
      double eyelid. Combined epicanthoplasty and double eyelidplasty need to be
      considered as one complete and inseparable procedure in surgery of the Asian eye.

PMID- 26306085
TI  - Volume Augmentation in the Lower Eyelid and Cheek Areas.
AB  - Many East Asians experience lower eyelid bulging and discoloration, and this is
      seen even in young individuals. The condition is caused by an undergrowth of the
      maxilla and not by aging. In this condition, the orbit appears small and the
      infraorbital rim is hypoplastic. This inevitably causes a depressed, tired, and
      sad appearance. Here, the authors present techniques of volume augmentation in
      the lower eyelid and cheek areas to rejuvenate the midface in Asians. 

PMID- 26306086
TI  - Aging Asian Upper Blepharoplasty and Brow.
AB  - The preoperative comprehensive evaluation of aging Asian patients seeking an
      Asian upper blepharoplasty and brow lift is imperative and should be performed
      meticulously. There are many methods of upper Asian face rejuvenation. Among
      them, the proper selection of operative technique is necessary. The operative
      technique for an aging Asian upper blepharoplasty and brow lift should be
      performed based on anatomical structures and their relationship. Modifications to
      the procedure are correlated with the degree of periorbital aging. The height of
      double fold in an aging Asian upper blepharoplasty should not exceed 10 mm from
      the eyelid margin when the eye is closed. The preservation of orbital fat during
      a blepharoplasty is needed for the prevention of periorbital hollowing, which
      looks older. For satisfactory results in aging Asian upper blepharoplasty and
      brow lift, the harmonization of the position of the upper eyelid and eyebrow is
      important. Noninvasive rejuvenation such as botulinum toxin and filler are good
      options for facial rejuvenation. 

PMID- 26306087
TI  - Revision Upper Blepharoplasty.
AB  - The ideal shape and height of the double eyelid varies widely depending on the
      patient and the culture. Patients may be dissatisfied after a double eyelid
      operation for the following reasons: scar, low versus high fold, shallow versus
      deep fold, triple folds, pretarsal fullness, ptosis, and asymmetry. Here the
      author describes the complications experienced after double eyelid surgery and
      corrective procedures. 

PMID- 26306088
TI  - Survey of background scattering from materials found in small-angle neutron
      scattering.
AB  - Measurements and calculations of beam attenuation and background scattering for
      common materials placed in a neutron beam are presented over the temperature
      range of 300-700 K. Time-of-flight (TOF) measurements have also been made, to
      determine the fraction of the background that is either inelastic or quasi
      elastic scattering as measured with a 3He detector. Other background sources
      considered include double Bragg diffraction from windows or samples, scattering
      from gases, and phonon scattering from solids. Background from the residual air
      in detector vacuum vessels and scattering from the 3He detector dome are
      presented. The thickness dependence of the multiple scattering correction for
      forward scattering from water is calculated. Inelastic phonon background
      scattering at small angles for crystalline solids is both modeled and compared
      with measurements. Methods of maximizing the signal-to-noise ratio by material
      selection, choice of sample thickness and wavelength, removal of inelastic
      background by TOF or Be filters, and removal of spin-flip scattering with
      polarized beam analysis are discussed.

PMID- 26306089
TI  - Methods for analysis of size-exclusion chromatography-small-angle X-ray
      scattering and reconstruction of protein scattering.
AB  - Size-exclusion chromatography in line with small-angle X-ray scattering (SEC
      SAXS) has emerged as an important method for investigation of heterogeneous and
      self-associating systems, but presents specific challenges for data processing
      including buffer subtraction and analysis of overlapping peaks. This paper
      presents novel methods based on singular value decomposition (SVD) and Guinier
      optimized linear combination (LC) to facilitate analysis of SEC-SAXS data sets
      and high-quality reconstruction of protein scattering directly from peak regions.
      It is shown that Guinier-optimized buffer subtraction can reduce common
      subtraction artifacts and that Guinier-optimized linear combination of
      significant SVD basis components improves signal-to-noise and allows
      reconstruction of protein scattering, even in the absence of matching buffer
      regions. In test cases with conventional SAXS data sets for cytochrome c and SEC
      SAXS data sets for the small GTPase Arf6 and the Arf GTPase exchange factors Grp1
      and cytohesin-1, SVD-LC consistently provided higher quality reconstruction of
      protein scattering than either direct or Guinier-optimized buffer subtraction.
      These methods have been implemented in the context of a Python-extensible Mac OS
      X application known as Data Evaluation and Likelihood Analysis (DELA), which
      provides convenient tools for data-set selection, beam intensity normalization,
      SVD, and other relevant processing and analytical procedures, as well as
      automated Python scripts for common SAXS analyses and Guinier-optimized
      reconstruction of protein scattering.

PMID- 26306090
TI  - Computation of diffuse scattering arising from one-phonon excitations in a
      neutron time-of-flight single-crystal Laue diffraction experiment.
AB  - Direct phonon excitation in a neutron time-of-flight single-crystal Laue
      diffraction experiment has been observed in a single crystal of NaCl. At room
      temperature both phonon emission and excitation leave characteristic features in
      the diffuse scattering and these are well reproduced using abinitio phonons from
      density functional theory (DFT). A measurement at 20 K illustrates the effect of
      thermal population of the phonons, leaving the features corresponding to phonon
      excitation and strongly suppressing the phonon annihilation. A recipe is given to
      compute these effects combining DFT results with the geometry of the neutron
      experiment.

PMID- 26306091
TI  - Programming new geometry restraints: parallelity of atomic groups.
AB  - Improvements in structural biology methods, in particular crystallography and
      cryo-electron microscopy, have created an increased demand for the refinement of
      atomic models against low-resolution experimental data. One way to compensate for
      the lack of high-resolution experimental data is to use a priori information
      about model geometry that can be utilized in refinement in the form of
      stereochemical restraints or constraints. Here, the definition and calculation of
      the restraints that can be imposed on planar atomic groups, in particular the
      angle between such groups, are described. Detailed derivations of the restraint
      targets and their gradients are provided so that they can be readily implemented
      in other contexts. Practical implementations of the restraints, and of associated
      data structures, in the Computational Crystallography Toolbox (cctbx) are
      presented.

PMID- 26306093
TI  - BINoculars: data reduction and analysis software for two-dimensional detectors in
      surface X-ray diffraction.
AB  - BINoculars is a tool for data reduction and analysis of large sets of surface
      diffraction data that have been acquired with a two-dimensional X-ray detector.
      The intensity of each pixel of a two-dimensional detector is projected onto a
      three-dimensional grid in reciprocal-lattice coordinates using a binning
      algorithm. This allows for fast acquisition and processing of high-resolution
      data sets and results in a significant reduction of the size of the data set. The
      subsequent analysis then proceeds in reciprocal space. It has evolved from the
      specific needs of the ID03 beamline at the ESRF, but it has a modular design and
      can be easily adjusted and extended to work with data from other beamlines or
      from other measurement techniques. This paper covers the design and the
      underlying methods employed in this software package and explains how BINoculars
      can be used to improve the workflow of surface X-ray diffraction measurements and
      analysis.

PMID- 26306094
TI  - Xtal-xplore-R: a graphical tool for exploring the residual function involved in
      crystal structure determination.
AB  - This work presents Xtal-xplore-R, a tool dedicated to the visualization of two
      dimensional cuts through the multidimensional crystallographic residual function.
      It imports arbitrary crystal structures, generates artificial diffraction data,
      and calculates and investigates the residual function in parameter space. The
      program serves two major purposes. Firstly, it is part of a more general project
      dealing with structure determination via global optimization techniques. In this
      context, the tool is being used to systematically analyse characteristic
      universal features of the target function (residual function) which can be used
      to develop appropriate problem-specific heuristic optimization algorithms.
      Secondly, Xtal-xplore-R is intended as a didactic tool to visualize how changes
      in atom parameters affect the residual function and can be used to demonstrate
      manual structure optimization for simple crystal structures.

PMID- 26306092
TI  - TEMPy: a Python library for assessment of three-dimensional electron microscopy
      density fits.
AB  - Three-dimensional electron microscopy is currently one of the most promising
      techniques used to study macromolecular assemblies. Rigid and flexible fitting of
      atomic models into density maps is often essential to gain further insights into
      the assemblies they represent. Currently, tools that facilitate the assessment of
      fitted atomic models and maps are needed. TEMPy (template and electron microscopy
      comparison using Python) is a toolkit designed for this purpose. The library
      includes a set of methods to assess density fits in intermediate-to-low
      resolution maps, both globally and locally. It also provides procedures for
      single-fit assessment, ensemble generation of fits, clustering, and multiple and
      consensus scoring, as well as plots and output files for visualization purposes
      to help the user in analysing rigid and flexible fits. The modular nature of
      TEMPy helps the integration of scoring and assessment of fits into large
      pipelines, making it a tool suitable for both novice and expert structural
      biologists.

PMID- 26306095
TI  - A laboratory-based Laue X-ray diffraction system for enhanced imaging range and
      surface grain mapping.
AB  - Although CCD X-ray detectors can be faster to use, their large-area versions can
      be much more expensive than similarly sized photographic plate detectors. When
      indexing X-ray diffraction patterns, large-area detectors can prove very
      advantageous as they provide more spots, which makes fitting an orientation
      easier. On the other hand, when looking for single crystals in a polycrystalline
      sample, the speed of CCD detectors is more useful. A new setup is described here
      which overcomes some of the limitations of limited-range CCD detectors to make
      them more useful for indexing, whilst at the same time making it much quicker to
      find single crystals within a larger polycrystalline structure. This was done by
      combining a CCD detector with a six-axis goniometer, allowing the compilation of
      images from different angles into a wide-angled image. Automated scans along the
      sample were coupled with image processing techniques to produce grain maps, which
      can then be used to provide a strategy to extract single crystals from a
      polycrystal.

PMID- 26306096
TI  - Risk factors associated with asthma, atopic dermatitis and rhinoconjunctivitis in
      a rural Senegalese cohort.
AB  - BACKGROUND: The World Allergy Organization estimates that 40 % of the world's
      population is affected by allergic diseases. The International Study of Asthma
      and Allergies in Childhood has completed Phase III and it has now become clear
      that these diseases have increased in developing countries, especially Africa,
      where prevalence rates were formerly low. Despite an increase in studies in
      Africa, few sub-Saharan West African countries are represented; the focus has
      remained on urban populations and little attention has been paid to rural sub
      Saharan Africa. METHODS: We performed an allergy survey in a birth cohort of
      children aged less than 15 years in rural Senegal and implemented an ISAAC
      questionnaire. We carried out a complete blood count and serological analyses for
      IgE levels against common allergens and mosquito saliva. RESULTS: The prevalence
      rates of asthma, rhinoconjunctivitis (RC) and atopic dermatitis (AD) were 12.8,
      12.5 and 12.2 % respectively. Specific IgE (sIgE) levels against mosquito spp.
      salivary gland antigens were significantly associated with AD; sIgE levels
      against selected true grasses (Poaceae) were significantly associated with RC.
      sIgE levels against house dust mite spp. were not associated with asthma, but
      were significantly correlated with mosquito IgE levels. Such cross-reactivity may
      blur the association between HDM sIgE and asthma. Consumption of seafood, storing
      whey cream, using plant fibre bedding and presence of carpet were significantly
      associated with increased risk of RC. The association of seafood may be the
      result of histamine intoxication from molluscs prepared by putrefaction. Cat
      presence and dog contact were associated with increased risk of asthma. Cow
      contact was associated with increased risk of AD. CONCLUSIONS: Our allergy study
      in rural West Africa revealed lower prevalence rates than the majority of African
      urban settings. Although several associated known risk factors were identified,
      there were associations specific to the region. The identification of probable
      artefactual dietary phenomena is a challenge for robust diagnosis of allergic
      disease. The association AD with mosquito saliva, a common allergen in rural
      settings, warrants specific attention. Further studies in rural Africa are needed
      to address the aetiology of allergy in a non-urban environment.

PMID- 26306097
TI  - A review of the pattern of AIDS defining, HIV associated neoplasms and
      premalignant lesions diagnosed from 2000-2011 at Kenyatta National Hospital,
      Kenya.
AB  - BACKGROUND: Sub-Sahara Africa hosts up to 71 % of all HIV infected people in the
      world. With this high incidence of Human immunodeficiency virus ( HIV) comes the
      burden of co-morbidities such as malignant and premalignant lesions. Aids
      defining malignancies have been listed as Kaposi's sarcoma, Non-Hodgkin's
      lymphoma and invasive squamous cell carcinoma of the cervix. People with
      HIV/AIDS(PLWAS) have a higher risk of developing these neoplasms than the rest of
      the population. The pathogenesis of these neoplasms in people with HIV has been
      linked to immune suppression, persistent antigenic stimulation and cytokine
      dysregulation. Current study analyzes and presents the patterns and trends in the
      presentation of HIV related malignancies in patients diagnosed through
      histopathology at Kenyatta National Hospital. AIM: To describe the patterns of
      AIDS- defining and non-AIDS- defining malignancies and premalignant lesions 10
      years pre- and post HAART period at Kenyatta National hospital, Kenya. METHODS
      AND TECHNIQUES: This was a hospital based descriptive cross sectional study. The
      Formalin fixed paraffin embedded (FFPE) blocks and histological reports of
      patients diagnosed between 2000 and 2011 were traced from archives. The patients'
      demographic data and clinical presentation was entered in an excel spreadsheet
      and the diagnosis and coding confirmed by a histopathologist. The data was then
      cleaned and analyzed using SSPS version 17.0 Ink. RESULTS: A total of 173 lesions
      were reviewed and analyzed. Of these 118 (68 %) were from females and 55 from
      males (32 %). The male to female ratio was 1:2. The age range was from two to 56
      years with a median of 36 years. Kaposi sarcoma is the leading AIDS defining
      malignancy in Kenya while invasive squamous cell carcinoma of the conjunctiva is
      the leading non-AIDS defining malignancy. This is closely followed by invasive
      squamous cell carcinoma of the cervix and NHL. CONCLUSION: Kaposi sarcoma is the
      leading AIDS associated neoplasm in Kenya. Physicians and caretakers managing and
      following up on HIV/AIDS patients should look out for Kaposi sarcoma as a form of
      IRIS following the institution of HAART in all HIV/AIDS patients. The incidence
      of invasive squamous cell carcinoma of the conjunctiva is increasing in PLWAS in
      Kenya. There is therefore a need to introduce early screening programs for
      squamous intraepithelial neoplasm of the conjunctiva in HIV/AIDS patients.

PMID- 26306098
TI  - Positive parenting: a randomised controlled trial evaluation of the Parents Plus
      Adolescent Programme in schools.
AB  - BACKGROUND: The aim of this study was to evaluate the Parents Plus Adolescents
      Programme (PPAP)-a parent training course specifically targeting parents of young
      adolescents (aged 11-16 years)-when delivered as a preventative programme in
      community school settings. METHODS: A sample of 126 parents (mean age of children
      = 12.34 years; range = 10-16 years) were randomly assigned to either a treatment
      (PPAP; n = 82) or a waiting-list control condition (WC; n = 44). Analyses are
      based on a study-completer sample post-treatment (n = 109 parents: PPAP n = 70;
      WC n = 39) and sample at 6 month follow up (n = 42 parents). RESULTS: Both post
      treatment (between groups) and 6-month follow-up comparisons of study completers
      (within PPAP group) revealed significant positive effects of the parenting
      intervention with respect to adolescent behaviour problems and parenting stress.
      The post treatment comparisons demonstrated large effect sizes on global measures
      of child difficulties (partial eta squared = 0.15) and self-reported parent
      stress (partial eta squared = 0.22); there was a moderate effect size on the self
      reported parent satisfaction (partial eta squared = 0.13). CONCLUSIONS: This
      study provides preliminary evidence that PPAP may be an effective model of parent
      training implemented in a community-based setting. The strengths and limitations
      of the study are discussed.

PMID- 26306099
TI  - Home oxygen and domestic fires.
AB  - To highlight the risk of domestic fires in the home use of oxygenTo recommend
      measures to reduce the risk. 

PMID- 26306100
TI  - The national review of asthma deaths: what did we learn and what needs to change?
AB  - KEY POINTS: The 2014 UK National Review of Asthma Deaths identified potentially
      preventable factors in two-thirds of the medical records of cases scrutinised45%
      of people who died from asthma did not call for or receive medical assistance in
      their final fatal attackOverall asthma management, acute and chronic, in primary
      and secondary care was judged to be good in less than one-fifth of those who
      diedThere was a failure by doctors and nurses to identify and act on risk factors
      for asthma attacks and asthma deathThe rationale for diagnosing asthma was not
      evident in a considerable number of cases, and there were inaccuracies related to
      the completion of medical certificates of the cause of death in over half of the
      cases considered for the UK National Review of Asthma Deaths. EDUCATIONAL AIMS:
      To increase awareness of some of the findings of the recent UK National Review of
      Asthma Deaths and previous similar studiesTo emphasise the need for accurate
      diagnosis of asthma, and of the requirements for completion of medical
      certificates of the cause of deathTo consider areas for improving asthma care and
      prevention of attacks and avoidable deaths. SUMMARY: Despite the development and
      publication of evidence-based asthma guidelines nearly three decades ago,
      potentially preventable factors are repeatedly identified in studies of the care
      provided for patients who die from asthma. The UK National Review of Asthma
      Deaths (NRAD), a confidential enquiry, was no exception: major preventable
      factors were identified in two-thirds of asthma deaths. Most of these factors,
      such as inappropriate prescription and failure to provide patients with personal
      asthma action plans (PAAPs), could possibly have been prevented had asthma
      guidelines been implemented. NRAD involved in-depth scrutiny by clinicians of the
      asthma care for 276 people who were classified with asthma as the underlying
      cause of death in real-life. A striking finding was that a third of these
      patients did not actually die from asthma, and many had no recorded rationale for
      an asthma diagnosis. The apparent complacency with respect to asthma care,
      highlighted in NRAD, serves as a wake-up call for health professionals, patients
      and their carers to take asthma more seriously. Based on the NRAD evidence, the
      report made 19 recommendations for change. The author has selected six areas
      related to the NRAD findings for discussion and provides suggestions for change
      in the provision of asthma care. The six areas are: systems for provision and
      optimisation of asthma care, diagnosis, identifying risk, implementation of
      guidelines, improved patient education and self-management, and improved quality
      of completion of medical certificates of the cause of death.

PMID- 26306101
TI  - Real-world research and its importance in respiratory medicine.
AB  - EDUCATIONAL AIMS: To improve understanding of: The relative benefits and
      limitations of evidence derived from different study designs and the role that
      real-life asthma studies can play in addressing limitations in the classical
      randomised controlled trial (cRCT) evidence base.The importance of guideline
      recommendations being modified to fit the populations studied and the model of
      care provided in their reference studies. KEY POINTS: Classical randomised
      controlled trials (cRCTs) show results from a narrow patient group with a
      constrained ecology of care.Patients with "real-life" co-morbidities and
      lifestyle factors receiving usual care often have different responses to
      medication which will not be captured by cRCTs if they are excluded by strict
      selection criteria.Meta-analyses, used to direct guidelines, contain an inherent
      meta-bias based on patient selection and artificial patient care.Guideline
      recommendations should clarify where they related to cRCT ideals (in terms of
      patient populations, medical resources and care received) and could be enhanced
      through inclusion of evidence from studies designed to better model the
      populations and care approaches present in routine care. SUMMARY: Clinical
      practice requires a complex interplay between experience and training, research,
      guidelines and judgement, and must not only draw on data from traditional or
      classical randomised controlled trials (cRCTs), but also from pragmatically
      designed studies that better reflect real-life clinical practice. To minimise
      extraneous variables and to optimise their internal validity, cRCTs exclude
      patients, clinical characteristics and variations in care that could potentially
      confound outcomes. The result is that respiratory cRCTs often enrol a small, non
      representative subset of patients and overlook the important interplay and
      interactions between patients and the real world, which can effect treatment
      outcomes. Evidence from real-life studies (e.g. naturalistic or pragmatic
      clinical trials and observational studies encompassing healthcare database
      studies and cohort studies) can be combined with cRCT evidence to provide a
      fuller picture of intervention effectiveness and realistic treatment outcomes,
      and can provide useful insights into alternative management approaches in more
      challenging asthma patients. The Respiratory Effectiveness Group (REG), in
      collaboration with the European Academy of Allergy and Clinical Immunology
      (EAACI) and the European Respiratory Society (ERS), is developing quality
      appraisal tools and methods for integrating different sources of evidence. A
      REG/EAACI taskforce aims to help support future guideline developers to avoid a
      one-size-fits-all approach to recommendations and to tailor the conclusions of
      their meta-analyses to the populations under consideration.

PMID- 26306102
TI  - Optimising inhaled mannitol for cystic fibrosis in an adult population.
AB  - ABSTRACT: There has been remarkable progress in the treatment of cystic fibrosis
      (CF) patients over the past 20 years. However, limitations of standard therapies
      have highlighted the need for a convenient alternative treatment to effectively
      target the pathophysiologic basis of CF-related disease by improving mucociliary
      clearance of airway secretions and consequently improve lung function and reduce
      respiratory exacerbations. Mannitol is an osmotic agent available as a dry
      powder, dispensed in a convenient disposable inhaler device for the treatment of
      adult patients with CF. Inhalation of mannitol as a dry powder is thought to
      change the viscoelastic properties of airway secretions, increase the hydration
      of the airway surface liquid and contribute to increased mucociliary and cough
      clearance of retained secretions. In two large phase 3 studies [1, 2], long-term
      use of inhaled mannitol resulted in a significant and clinically meaningful
      improvement in lung function relative to control in adult CF subjects and had an
      acceptable safety profile. Clinical experience with inhaled mannitol confirms
      that it is safe and effective. A minority of patients are unable to tolerate the
      medication. However, through training in proper inhaler technique and setting
      clear expectations regarding therapeutic effects, both the tolerance and
      adherence necessary for long term efficacy can be positively influenced.
      EDUCATIONAL AIMS: To discuss the importance of airway clearance treatments in the
      management of cystic fibrosis.To describe the clinical data that supports the use
      of mannitol in adult patients with cystic fibrosis.To highlight the role of
      mannitol tolerance testing in screening for hyperresponsiveness.To provide
      practical considerations for patient education in use of mannitol inhaler. KEY
      POINTS: Inhaled mannitol is a safe and effective option in adult patients with
      cystic fibrosis.Mannitol tolerance testing effectively screens for
      hyperresponsiveness prior to initiation of therapy.Physiotherapists and
      respiratory therapists play an integral role in the introduction and maintenance
      of dry powder inhalation therapy.Patient training and follow-up is important for
      optimising longer term adherence.

PMID- 26306103
TI  - Introducing a core curriculum for respiratory sleep practitioners.
AB  - The background and purpose of the HERMES (Harmonising Education in Respiratory
      Medicine for European Specialists) initiative has been discussed at length in
      previous articles [1-3]. This article aims to provide more detailed and specific
      insight into the process and methodology of the Sleep HERMES Task Force in
      developing a core curriculum in respiratory sleep medicine. 

PMID- 26306104
TI  - Measuring lung function using sound waves: role of the forced oscillation
      technique and impulse oscillometry system.
AB  - Measuring lung function is an important component in the decision making process
      for patients with obstructive airways disease (OAD). Not only does it help in
      arriving at a specific diagnosis, but it also helps in evaluating severity so
      that appropriate pharmacotherapy can be instituted, it helps determine prognosis
      and it helps evaluate response to therapy. Spirometry is currently the most
      commonly performed lung function test in clinical practice and is considered to
      be the gold standard diagnostic test for asthma and COPD. However, spirometry is
      not an easy test to perform because the forceful expiratory and inspiratory
      manoeuvres require good patient co-operation. Children aged <5 years, elderly
      people and those with physical and cognitive limitations cannot perform
      spirometry easily. 

PMID- 26306106
TI  - Living with the challenges of treating tuberculosis: The patient and healthcare
      professional perspective.
AB  - As parents, we found it very difficult to deal with the fact that our child had
      tuberculosis (TB). It was not just the shocking diagnosis, but the whole
      experience involving treatment and medical examinations is one we would rather
      leave behind us. 

PMID- 26306105
TI  - Case report: Sudden cardiac death in a young man.
AB  - A 35-year-old man presented to the accident and emergency department with history
      of productive cough, breathlessness and some weight loss over several weeks. He
      had a past medical history of asthma and eczema. He mentioned that, at times, he
      had been expectorating sputum with some haemoptysis over the past few months. He
      was of Bangladeshi origin, but had been resident in the UK since 1986 and last
      visited Bangladesh a year ago. He was a smoker of 10-15 cigarettes per day. He
      also admitted to smoking heroin. In addition to his respiratory symptoms he also
      complained of vomiting, which was precipitated by eating. He denied bowel or
      urinary symptoms. 

PMID- 26306107
TI  - The second year has been completed: News from the Underground.
AB  - Among many other things, the last European Respiratory Society (ERS)
      International Congress in Munich brought changes to the ERS Junior Members
      Committee (JMC). The 3-year term of JMC representatives has seen Indre Butiene,
      who initiated the Committee 3 years ago, finish her tenure as chair, with Anders
      Bjerg, respiratory epidemiologist from Gothenburg, Sweden, being elected as her
      replacement. Indre's departure has also led to the election of a new
      representative to the ERS Education Council. We congratulate Agnes Boots from the
      Netherlands on her election to this important position! Also, here in Breathe,
      the Doing Science series has been taken over by Georgia Hardavella, UK, whose
      ideas will take this practical educational series to new levels in 2015. The Hot
      Topics section is now coordinated by Neil Saad, UK, one of many Juniors outside
      the JMC who have volunteered for different JMC activities. 

PMID- 26306108
TI  - Doing Science: managing colleagues and collaborations in scientific research.
AB  - Talent, dedication and organisational skills play a pivotal role in the success
      of scientific and clinical research. However, your capacity to flourish and
      succeed is often affected by your professional relationships with your peers and
      bosses. Throughout your career, you will be faced (if not already) with a variety
      of awkward interpersonal situations. This is the point where sophisticated
      management skills are required to tackle difficulties and smooth out any rough
      edges that can potentially roadblock your research. 

PMID- 26306109
TI  - Hot topics from the Assemblies.
AB  - INSTEAD: a randomised switch trial of indacaterol versus salmeterol/fluticasone
      in moderate COPD Authors: Rossi A, van der Molen T, Ricardo del Olmo, et al. Eur
      Respir J 2014; 44: 6, 1548-1556 SUMMARY: Inhaled corticosteroids (ICS) remain a
      highly controversial treatment for stable chronic obstructive pulmonary disease
      (COPD). Data linking high-dose ICS with complications, such as pneumonia and
      fractures, has necessitated a re-evaluation of their role in COPD management.
      Guidelines currently suggest ICS for patients with a forced expiratory volume in
      1 s (FEV1) <50% predicted (or <60% in some regions) and a history of
      exacerbations. Nevertheless, it is well known that ICS and combination ICS/long
      acting beta-agonist (LABA) treatments are commonly used outside these groups. In
      view of the increasingly recognised dangers of ICS treatment, data demonstrating
      the safety of discontinuing ICS treatment is welcome. 

PMID- 26306110
TI  - Supported self-management for asthma.
AB  - KEY POINTS: Self-management education in asthma is not an optional extra.
      Healthcare professionals have a responsibility to ensure that everyone with
      asthma has personalised advice to enable them to optimise how they self-manage
      their condition.Overviews of the extensive evidence-base conclude that asthma
      self-management supported by regular professional review, improves asthma
      control, reduces exacerbations and admissions, and improves quality of life.Self
      management education should be reinforced by a written personalised asthma action
      plan which provides a summary of the regular management strategy, how to
      recognise deterioration and the action to take.Successful implementation combines
      education for patients, skills training for professionals in the context of an
      organisation committed to both the concept and the practice of supported self
      management. EDUCATIONAL AIMS: To summarise the evidence base underpinning
      supported self-management for asthmaTo provide clinicians with a practical
      approach to providing supported self-management for asthmaTo suggest an
      appropriate strategy for implementing supported self-management. SUMMARY: The
      evidence in favour of supported self-management for asthma is overwhelming. Self
      management including provision of a written asthma action plan and supported by
      regular medical review, almost halves the risk of hospitalisation, significantly
      reduces emergency department attendances and unscheduled consultations, and
      improves markers of asthma control and quality of life. Demographic and cultural
      tailoring enables effective programmes to be implemented in deprived and/or
      ethnic communities or within schools. A crucial component of effective asthma
      self-management interventions is the provision of an agreed, written personalised
      action plan which advises on using regular medication, recognising deterioration
      and appropriate action to take. Monitoring can be based on symptoms or on peak
      flows and should specify thresholds for action including increasing inhaled
      steroids, commencing oral steroids, and when (and how) to seek professional help.
      Plans should be personalised to reflect asthma severity and treatment regimes,
      avoidance of triggers, co-morbid rhinitis and the individual's preferences.
      Implementation is a challenge. Systematic review evidence suggests that it is
      possible to implement asthma self-management in routine care, but that to be
      effective this requires a whole systems approach which considers implementation
      from the perspective of patient education and resources, professional skills and
      motivation and organisation priorities and routines.

PMID- 26306111
TI  - Inhaled therapy in cystic fibrosis: agents, devices and regimens.
AB  - KEY POINTS: There have been significant advances in both inhalation medicines and
      delivery devices with "intelligent nebulisers" and "dry-powder inhalers" becoming
      commonplace in CF care.Inhaled medicines generate high levels of a drug within
      the airways with limited systemic effects, offering safe and convenient
      antibiotic and mucolytic therapy for individuals with CF.Variations in adherence
      are not unique to CF; however, treatment burden is high and therefore fast
      inhaled drug delivery devices may assist individuals in completing the prescribed
      treatment regimes.Prescribers of inhaled medicines have a responsibility to
      consider, in addition to efficacy, the appropriated drug/device combination for
      each individual in order to promote adherence and achieve the desired clinical
      benefit. SUMMARY: The recognised mainstay daily treatments for cystic fibrosis
      (CF) focus on inhaled and oral medications, airway clearance and optimised
      nutrition. This review discusses recent advances in inhaled therapies for the
      management of CF, including devices such as intelligent nebulisers, drug
      formulations and supporting evidence for inhaled antibiotics (for the management
      of chronic Pseudomonas aeruginosa) and muco-active drugs. We include practical
      advice for clinicians regarding the optimisation of inhalation technique and
      education. The influence of adherence on the use of inhaled therapies in CF is
      also reviewed. EDUCATIONAL AIMS: To inform readers about the history and
      progression of inhaled therapies for people with CF with reference to the
      literature supporting current practice.To highlight the factors that may impact
      the success of inhaled therapies, including those which are device specific such
      as drug deposition and those which influence adherence.

PMID- 26306112
TI  - Physiological basis of cardiopulmonary rehabilitation in patients with lung or
      heart disease.
AB  - EDUCATIONAL AIMS: To illustrate the common mechanisms limiting exercise tolerance
      in patients with chronic lung and heart diseaseTo highlight the impact of lung
      and heart disease on daily physical activity levelsTo outline the effects of
      cardiopulmonary rehabilitation on functional capacity in patients with chronic
      lung and heart diseaseTo discuss an innovative tele-rehabilitation intervention
      using information and communications technologies to improve functional capacity
      in patients with chronic lung and heart disease. SUMMARY: Shortness of breath
      associated with cardiorespiratory abnormalities and peripheral muscle discomfort
      are the major factors that limit exercise capacity in patients with chronic
      obstructive pulmonary disease (COPD) and those with congestive heart failure
      (CHF). Both of these symptoms negatively impact on patients' daily physical
      activity levels. In turn, poor daily physical activity is commonly associated
      with increased rates of morbidity and mortality. Cardiopulmonary rehabilitation
      programmes partially reverse muscle weakness and dysfunction and increase
      functional capacity in both COPD and CHF. However, benefits gained from
      participation in cardiopulmonary rehabilitation programmes are regressing soon
      after the completion of these programmes. Moreover, several barriers limit access
      and uptake of cardiopulmonary rehabilitation programmes by eligible patients. A
      potential solution to the underutilisation of cardiopulmonary rehabilitation is
      the implementation of tele-rehabilitation interventions at home using information
      and communications technologies. Thus, tele-rehabilitation may be useful to
      encourage and educate patients with COPD or CHF on how best to maintain and/or
      further enhance daily physical activity levels.

PMID- 26306113
TI  - How to carry out a field walking test in chronic respiratory disease.
AB  - EDUCATIONAL AIMS: To provide recommendations for conducting field walking tests
      in people with chronic respiratory disease, from the new European Respiratory
      Society/American Thoracic Society Technical StandardTo provide information to
      assist in selecting a field walking test in people with chronic respiratory
      disease. KEY POINTS: The 6MWT, ISWT and ESWT are valid and reliable tests of
      functional exercise capacity in people with COPD. The 6MWT is also widely used in
      other chronic respiratory disorders.There is a learning effect for the 6MWT and
      ISWT, so two tests must be performed if the tests are being used to measure
      change over time, with the best distance recorded.The 6MWT is very sensitive to
      changes in the way it is conducted, including use of encouragement, provision of
      supplemental oxygen, changes in track layout and length, and use of wheeled
      walkers. These factors should be held constant when the test is repeated.The
      6MWT, ISWT and ESWT are strenuous tests, with cardiorespiratory responses that
      are similar to those during a maximal incremental exercise test. As a result, the
      contraindications and precautions for these field walking tests should be the
      same as for a laboratory-based incremental exercise test. SUMMARY: The European
      Respiratory Society (ERS) and American Thoracic Society (ATS) have recently
      published a Technical Standard which documents the standard operating procedures
      for the 6-min walk test (6MWT), incremental shuttle walk test (ISWT) and
      endurance shuttle walk test (ESWT). The Technical Standard shows that all three
      tests are valid and reliable measures of functional exercise capacity in people
      with chronic respiratory disease and makes recommendations for standardising
      their performance. Key findings and recommendations of the Technical Standard
      include: The 6MWT, ISWT and ESWT are strenuous tests which elicit
      cardiorespiratory responses that are similar to those observed during a maximal
      incremental exercise test. As a result, the contraindications and precautions for
      field walking tests should be consistent with those used for a laboratory-based
      incremental exercise test.There is strong evidence of a learning effect for the
      6MWT and ISWT. Two tests should be performed when the 6MWT or ISWT are used to
      measure change over time.The 6MWT, ISWT and ESWT are responsive to treatment
      effects in people with chronic respiratory disease, particularly for
      rehabilitation.The 6MWT is very sensitive to variations in methodology, including
      use of encouragement, provision of supplemental oxygen, changes in track layout
      and length, and use of wheeled walkers. These factors should be documented and
      held constant on repeat testing.The lowest S pO2 recorded during a 6MWT is an
      important marker of disease severity and prognosis. Continuous pulse oximetry is
      recommended during the 6MWT, to ensure that the lowest S pO2 is recorded.In
      adults with chronic respiratory disease, a change in 6-min walk distance of 30 m
      or more indicates a clinically significant change has occurred.

PMID- 26306114
TI  - An unusual case of breathlessness in a patient with chronic myeloid leukaemia:
      Case Report.
AB  - A 67-year-old Caucasian male presented in January, 2013, with difficulty in
      breathing and pyrexia. This was following a course of antibiotics for a previous
      chest infection that had begun at the beginning of January and had not responded
      to therapy. His past medical history included chronic myeloid leukaemia, basal
      cell carcinoma of the throat treated in 2011, glaucoma and bilateral inguinal
      hernia repair (performed in 1989 and 2008). He was an ex-smoker of 21 years. His
      current medication was dasatinib (tyrosine kinase inhibitor) 100 ug?day(-1),
      amoxicillin/clavulanic acid 625 mg three-times daily orally (changed to 1.2 g
      three-times daily intravenously) and bimatoprost 0.1 mg eye drops. 

PMID- 26306115
TI  - Sleep apnoea and telemonitoring: The patient and healthcare professional
      perspective.
AB  - I started experiencing symptoms of extreme tiredness and severe lethargy about 18
      years ago, a short while after an angina attack. I thought the symptoms were
      related to my angina and I did not immediately seek help. 

PMID- 26306116
TI  - 13th ERS Lung Science Conference. The most important take home messages: News
      from the Underground.
AB  - The 13th ERS Lung Science Conference (LSC) was organised to bring academics
      together from all over the world to present and discuss the latest developments
      regarding lung infection and immunity. The conference took place in breathtaking
      Estoril, Portugal; however, it wasn't the beautiful surroundings that were our
      main motivation to attend, but instead the scientific merit of the conference and
      the chance to create new scientific collaborations. The scientific programme [1]
      was packed with the most up-to-date content in the field of lung infection and
      immunity and included some of the top researchers within this exciting area.
      Moreover, the convenient size of the LSC offered the opportunity to renew and
      intensify friendships and collaborations. In particular, for researchers at the
      start of their career, this is a great feature and we therefore warmly recommend
      the LSC to ERS Juniors Members! 

PMID- 26306118
TI  - Hot topics from the Assemblies.
AB  - The accuracy of non-small cell lung cancer (NSCLC) staging is fundamental for the
      management of lung cancer patients. Visceral pleural invasion (VPI) is a poor
      prognostic factor in NSCLC. Its presence results in upstaging of tumours <3 cm
      according to the American Joint Committee on Cancer (AJCC) TNM staging system.
      However, the role of VPI as an independent prognostic factor in tumours <7 cm is
      unclear. 

PMID- 26306119
TI  - GPs Meet Rare Lung Disorders Task Force factsheet: primary ciliary dyskinesia.
AB  - Primary ciliary dyskinesia (PCD) is a rare, autosomal recessive disease of
      abnormalities of ciliary structure and function. The result is impaired
      mucociliary clearance, causing a variety of respiratory symptoms, and likely
      progression to bronchiectasis in most cases. Situs anomalies are present in
      nearly 50% of cases. 

PMID- 26306117
TI  - Doing science: how to get credit for your scientific work.
AB  - Everyone deserves to be acknowledged for their efforts and contributions to a
      shared goal, and getting credit for your scientific work should be part of a
      natural process and should be fair and straightforward. However, credit cannot be
      objectively measured despite it having a big influence and, unfortunately,
      getting appropriate credit can occasionally be both complicated and challenging. 

PMID- 26306120
TI  - Dr. Miguel Valderrabano Spearheads Special Issue on Cardiac Electrophysiology for
      the Methodist Debakey Cardiovascular Journal.

PMID- 26306121
TI  - The Current State of Cardiac Electrophysiology.

PMID- 26306122
TI  - Catheter Ablation of Paroxysmal Atrial Fibrillation: Have We Achieved Cure with
      Pulmonary Vein Isolation?
AB  - Pulmonary vein isolation (PVI) is the cornerstone of current ablation techniques
      to eliminate atrial fibrillation (AF), with the greatest efficacy as a stand
      alone procedure in patients with paroxysmal AF. Over the years, techniques for
      PVI have undergone a profound evolution, and current guidelines recommend PVI
      with confirmation of electrical isolation. Despite significant efforts, PV
      reconnection is still the rule in patients experiencing post-ablation arrhythmia
      recurrence. In recent years, use of general anesthesia with or without jet
      ventilation, open-irrigated ablation catheters, and steerable sheaths have been
      demonstrated to increase the safety and efficacy of PVI, reducing the rate of PV
      reconnection over follow-up. The widespread clinical availability of ablation
      catheters with real-time contact force information will likely further improve
      the effectiveness and safety of PVI. In a small but definite subset of patients,
      post-ablation recurrent arrhythmia is due to non-PV triggers, which should be
      eliminated in order to improve success. Typically, non-PV triggers cluster in
      specific regions such as the coronary sinus, the inferior mitral annulus, the
      interatrial septum, the left atrial appendage, the Eustachian ridge, the crista
      terminalis region, the superior vena cava, and the ligament of Marshall. Focal
      ablation targeting the origin of the trigger is recommended in most cases.
      Empirical non-PV ablation targeting the putative substrate responsible for AF
      maintenance with ablation lines and/or elimination of complex fractionated
      electrograms has not been shown to improve success compared to PVI alone.
      Similarly, the role of novel substrate-based ablation approaches targeting
      putative localized sources of AF (e.g., rotors) identified by computational
      mapping techniques is unclear, as they have never been compared to PVI and non-PV
      trigger ablation in an adequately designed randomized trial. This review
      highlights PVI techniques and outcomes in treating recurrent drug-refractory AF
      and discusses the potential role of additional non-PV ablation. 

PMID- 26306123
TI  - Ablating Atrial Fibrillation: Customizing Lesion Sets Guided by Rotor Mapping.
AB  - Ablation occupies an increasing role in the contemporary management of atrial
      fibrillation (AF), but results are suboptimal, particularly for persistent AF.
      While an anatomic approach to ablation is a highly efficacious and safe method to
      isolate pulmonary vein (PV) triggers, recurrence of AF is not always associated
      with PV reconnection, and there is compelling evidence that non-PV sites sustain
      AF after it is triggered. Recent developments in wide-area mapping and signal
      processing now identify rotors in the vast majority of AF patients that sustain
      AF and whose elimination improves long-term freedom from AF in multicenter
      studies. Investigators have now demonstrated rotor and focal sources for AF that
      show many analogous properties between approaches: they lie in spatially
      reproducible regions temporally over hours to days, and they are amenable to
      targeted ablation. This review outlines the rationale and technical developments
      supporting this mechanistic paradigm for human AF, and discusses how rotor
      mapping may be implemented for individual patient customization of lesion sets.
      Mechanistic studies are required to explain why rotor elimination (or other
      ablation approaches) producing long-term elimination of AF may not always
      terminate AF acutely, how AF correlates with structural changes on magnetic
      resonance imaging, and how these findings can be integrated clinically with
      current ablation strategies to improve patient outcomes. 

PMID- 26306124
TI  - Is the Atrial Neural Plexis a Therapeutic Target in Atrial Fibrillation?
AB  - Circumferential pulmonary vein isolation is the mainstay of atrial fibrillation
      (AF) ablation, but alternative approaches and techniques have been developed to
      improve the outcomes. One of these additional ablation targets are ganglionated
      plexi of the intrinsic cardiac autonomic system that contain a variety of
      sympathetic and parasympathetic neurons that communicate with the extrinsic
      cardiac autonomic nervous system. The ganglionated plexi of the heart do not
      serve as a simple relay station but could modulate the autonomic interaction
      between the extrinsic and intrinsic cardiac autonomic system. Intrinsic cardiac
      autonomic nerve activity is an invariable trigger of paroxysmal atrial
      tachyarrhythmia, including atrial fibrillation. Although multiple studies have
      shown that ganglionated plexi play an important role in initiating atrial
      fibrillation, there is no consensus on a standardized protocol for selecting
      target sites and determining how ganglionated plexi ablation can best be
      accomplished. Recent clinical trials have demonstrated the feasibility and
      efficacy of ganglionated plexi ablation in addition to pulmonary vein isolation,
      but novel technologies and strategies are necessary to improve the current
      ablation techniques in managing patients with atrial fibrillation. This review
      focuses on the relationship between atrial ganglionated plexi and atrial
      fibrillation and the potential benefits and limitations of ganglionated plexi
      ablation in the management of atrial fibrillation. 

PMID- 26306125
TI  - Catheter Ablation for Long-Standing Persistent Atrial Fibrillation.
AB  - Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide and
      represents a major burden to health care systems. Atrial fibrillation is
      associated with a 4- to 5-fold increased risk of thromboembolic stroke. The
      pulmonary veins have been identified as major sources of atrial triggers for AF.
      This is particularly true in patients with paroxysmal AF but not always the case
      for those with long-standing persistent AF (LSPAF), in which other locations for
      ectopic beats have been well recognized. Structures with foci triggering AF
      include the coronary sinus, the left atrial appendage (LAA), the superior vena
      cava, the crista terminalis, and the ligament of Marshall. More than 30 studies
      reporting results on radiofrequency ablation of LSPAF have been published to
      date. Most of these are observational studies with very different methodologies
      using different strategies. As a result, there has been remarkable variation in
      short- and long-term success, which suggests that the optimal ablation technique
      for LSPAF is still to be elucidated. In this review we discuss the different
      approaches to LSPAF catheter ablation, starting with pulmonary vein isolation
      (PVI) through ablation lines in different left atrial locations, the role of
      complex fractionated atrial electrograms, focal impulses and rotor modulation,
      autonomic modulation (ganglionated plexi), alcohol ablation, and the future of
      epicardial mapping and ablation for this arrhythmia. A stepwise ablation approach
      requires several key ablation techniques, such as meticulous PVI, linear ablation
      at the roof and mitral isthmus, electrogram-targeted ablation with particular
      attention to triggers in the coronary sinus and LAA, and discretionary right
      atrial ablation (superior vena cava, intercaval, or cavotricuspid isthmus lines).

PMID- 26306126
TI  - Percutaneous Left Atrial Appendage Ligation for Stroke Prevention in Atrial
      Fibrillation.
AB  - Prevention of thromboembolic complications in atrial fibrillation remains a
      tremendous clinical challenge. Knowledge that the left atrial appendage (LAA) is
      the most common anatomical origin of cardioembolic strokes1 has been the main
      motivation to develop clinical and procedural strategies to exclude the LAA from
      the circulation, either surgically or percutaneously. This review discusses the
      rationale behind these strategies, their relative merits, and future prospects
      for LAA exclusion strategies. 

PMID- 26306127
TI  - The Left Atrial Appendage: Target for Stroke Reduction in Atrial Fibrillation.
AB  - A patient with atrial fibrillation (AF) has a greater than 5% annual risk of
      major stroke, a 5-fold increase compared to the general population. While
      anticoagulation remains the standard stroke prevention strategy, the nature of
      lifelong anticoagulation inevitably carries an increased risk of bleeding,
      increased stroke during periods of interruption, increased cost, and significant
      lifestyle modification. Many patients with atrial fibrillation have had their
      left atrial appendage (LAA) ligated or excised by surgeons during cardiac
      surgery, a decision based largely on intuition and with no clear evidence of
      efficacy in stroke risk reduction. The observation that 90% of the thrombi found
      in nonvalvular AF patients and 57% found in valvular AF are in the LAA, triggered
      significant interest in the LAA as a potential therapeutic target. Until
      recently, the results were inconsistent, and high rates of incomplete occlusions
      precluded the medical community from confirming a definite relationship between
      LAA and stroke. As a result, anticoagulation is still the recommended first-line
      stroke risk reduction in AF, and the American College of Cardiology/American
      Heart Association guidelines recommend LAA exclusion only with surgical ablation
      of AF or in the context of concomitant mitral valve surgery. A handful of devices
      have been developed for LAA exclusion. This includes percutaneous options such as
      WATCHMANTM Left Atrial Appendage Closure Device (Boston Scientific Corporation,
      Marlborough, MA), hybrid epicardial devices such as the LARIAT Suture Delivery
      Device (SentreHEART, Inc., Redwood City, CA), and epicardial surgical devices
      such as AtriClip(r) LAA Occlusion System (AtriCure, Inc., West Chester, OH).
      Studies of the Watchman device have shown noninferiority to Warfarin in stroke
      prevention and this device has recently gained approval from the U.S. Food and
      Drug Administration (FDA) following lengthy delays due to safety concerns. The
      Lariat device, which received 510K clearance by the FDA for tissue approximation
      but not LAA exclusion, has been the target of significant criticism due to
      serious procedural safety concerns and high incomplete closure rates. The
      surgical AtriClip has been FDA approved since 2009 and is currently the most
      widely used LAA exclusion device placed through an epicardial approach. Small
      studies have shown excellent reliability and success of complete LAA closure with
      the AtriClip device, which is implanted through an epicardial approach.
      Currently, we are conducting a multicenter trial to demonstrate the stroke
      prevention potential of this epicardial device through a short (45 minute), stand
      alone, minimally invasive procedure in lieu of lifelong anticoagulation in
      patients at high risk of bleeding. 

PMID- 26306128
TI  - Surgical Ablation of Atrial Fibrillation.
AB  - The Cox-maze procedure for the restoration of normal sinus rhythm, initially
      developed by Dr. James Cox, underwent several iterations over the years. The main
      concept consists of creating a series of transmural lesions in the right and left
      atria that disrupt re-entrant circuits responsible for propagating the abnormal
      atrial fibrillation rhythm. The left atrial appendage is excluded as a component
      of the Maze procedure. For the first three iterations of the Cox- maze procedure,
      these lesions were performed using a surgical cut-and-sew approach that ensured
      transmurality. The Cox-Maze IV is the most currently accepted iteration. It
      achieves the same lesion set of the Cox- maze III but uses alternative energy
      sources to create the transmural lesions, potentially in a minimally invasive
      approach on the beating heart. High-frequency ultrasound, microwave, and laser
      energy have all been used with varying success in the past. Today, bipolar
      radiofrequency heat or cryotherapy cooling are the most accepted sources for
      creating linear lesions with consistent safety and transmurality. The robust and
      reliable nature of these energy delivery methods has yielded a success rate
      reaching 90% freedom from atrial fibrillation at 12 months. Such approaches offer
      a significant long-term advantage over catheter-based ablation, especially in
      patients having longstanding, persistent atrial fibrillation with characteristics
      such as dilated left atrial dimensions, poor ejection fraction, and failed
      catheter ablation. Based on these improved results, there currently is
      significant interest in developing a hybrid ablation strategy that incorporates
      the superior transmural robust lesions of surgical ablation, the reliable stroke
      prevention potential of epicardial left atrial appendage exclusion, and
      sophisticated mapping and confirmatory catheter-based ablation technology. Such a
      minimally invasive hybrid strategy for ablation may lead to the development of
      multidisciplinary "Afib teams" to obtain optimal long-term sinus rhythm control.
      This article provides an overview of current surgical strategies for patients
      with atrial fibrillation and addresses the two main goals in its management. 

PMID- 26306129
TI  - Ablating Premature Ventricular Complexes: Justification, Techniques, and
      Outcomes.
AB  - We reviewed the underlying principles that allow for safe and effective ablation
      for premature ventricular complexes. Clinical scenarios that necessitate
      consideration for ablation, the underlying anatomy, and the unique consideration
      to maximize energy delivery without compromising safety are sequentially
      examined. 

PMID- 26306130
TI  - Radiofrequency Ablation to Prevent Sudden Cardiac Death.
AB  - Radiofrequency ablation may prevent or treat atrial and ventricular arrhythmias.
      Since some of these arrhythmias are associated with sudden cardiac death, it has
      been hypothesized that ablation may prevent sudden death in certain cases. We
      performed a literature search to better understand under which circumstances
      ablation may prevent sudden death and found little randomized data demonstrating
      the long-term effects of ablation. Current literature shows that ablation clearly
      prevents symptoms of arrhythmia and may reduce the incidence of sudden cardiac
      death in select patients, although data does not indicate improved mortality.
      Ongoing clinical trials are needed to better define the role of ablation in
      preventing sudden cardiac death. 

PMID- 26306131
TI  - Epicardial Ablation of Ventricular Tachycardia.
AB  - Epicardial mapping and ablation via a percutaneous subxiphoid technique has been
      instrumental in improving the working understanding of complex myocardial scars
      in various arrhythmogenic substrates. Endocardial ablation alone may not be
      sufficient in patients with ischemic cardiomyopathy, dilated cardiomyopathy,
      arrhythmogenic right ventricular cardiomyopathy, hypertrophic cardiomyopathy, and
      Chagas disease to prevent recurrent ventricular tachycardia. Multiple
      observational studies have demonstrated greater freedom from recurrence with
      adjunctive epicardial ablation compared with endocardial ablation alone. While
      epicardial ablation is performed predominantly at tertiary referral centers,
      knowledge of the technical approach, clinical indications, and potential
      complications is imperative to maximizing clinical success and patient safety. In
      1996, Sosa and colleagues modified the pericardiocentesis technique to enable
      percutaneous access to the pericardial space for mapping and catheter ablation of
      ventricular tachycardia.1 Originally developed for patients with epicardial
      scarring due to chagasic cardiomyopathy and patients with ischemic cardiomyopathy
      refractory to endocardial ablationm,2,3 this approach has since become an
      essential part of the armamentarium for the treatment of ventricular tachycardia.
      Myocardial scars are three-dimensionally complex with varying degrees of
      transmurality, and the ability to map and ablate the epicardial surface has
      contributed to a greater understanding of scar-related VT in postinfarction
      cardiomyopathy and nonischemic substrates including idiopathic dilated
      cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, hypertrophic
      cardiomyopathy, and chagasic cardiomyopathy. In this review, we highlight the
      percutaneous approach and discuss clinical indications and potential
      complications. 

PMID- 26306132
TI  - Case Report: A Rare Case of a Giant Right Coronary Artery Aneurysm.
AB  - We report the case of a 34-year-old female patient with a giant thrombus-filled
      aneurysm of the right coronary artery presenting as a spherical cardiac mass on
      echocardiography. The cardiac mass was found to be an 8-cm right coronary artery
      aneurysm on cardiac magnetic resonance imaging, which also revealed a 3.5-cm
      proximal left coronary aneurysm and a very small aneurysm at the origin of the
      obtuse marginal coronary artery. Due to the extent and size of the right coronary
      aneurysm, a decision for surgical intervention was made. Resection of the right
      coronary artery aneurysm with vein graft replacement and a bypass to the left
      anterior descending followed by subsequent exclusion of the aneurysm was
      successfully performed. 

PMID- 26306133
TI  - Case Report: Percutaneous Closure of an Ascending Aortic Pseudoaneurysm by 3D
      Angiography Guidance.

PMID- 26306135
TI  - Museum Image: Thoracic Outlet Syndrome.

PMID- 26306134
TI  - Case Report: En Bloc Resection of Pancoast Tumor with Adjuvant Aortic Endograft
      and Chemoradiation.
AB  - "Pancoast" tumors frequently require a multidisciplinary approach to therapy and
      are still associated with high morbidity and mortality. Due to their sensitive
      anatomic location, complex resections and chemoradiation regimens are typically
      required for treatment. Those with signs of aortic invasion pose an even greater
      challenge, given the added risks of cardiopulmonary bypass for aortic resection
      and interposition. Placement of an aortic endograft can facilitate resection if
      the tumor is in close proximity to or is invading the aorta. Prophylactic
      endografting to prevent radiation-associated aortic rupture has also been
      described. This case describes a 60-year-old female who presented with a stage
      IIIa left upper lobe undifferentiated non-small-cell carcinoma encasing the
      subclavian artery with thoracic aorta and bony invasion. Following carotid
      subclavian bypass with Dacron, en bloc resection of the affected lung, ribs, and
      vertebral bodies was performed. The aorta was prophylactically reinforced with a
      Gore TAG thoracic endograft prior to adjuvant chemoradiation. The patient remains
      disease-free at more than 5 years follow-up after completing her treatment
      course. Endovascular stenting with subsequent chemoradiation may prove to be a
      viable alternative to palliation or open operative management and prevention of
      aortic injury during tumor resection and/or adjuvant therapy in select patients
      with aortic involvement. 

PMID- 26306136
TI  - Museum Image: Multimodality Imaging of a Cardiac Pseudotumor.

PMID- 26306137
TI  - Points To Remember: Ophthalmologic Care in the Adult Patient.

PMID- 26306138
TI  - Poet's Pen: Appeal, in Three Downs.

PMID- 26306140
TI  - Essay On Being a Doctor: The Best Medicine at the End of Life.

PMID- 26306141
TI  - Anti program death-1/anti program death-ligand 1 in digestive cancers.
AB  - Human tumors tend to activate the immune system regulatory checkpoints as a means
      of escaping immunosurveillance. For instance, interaction between program death-1
      (PD-1) and program death-ligand 1 (PD-L1) will lead the activated T cell to a
      state of anergy. PD-L1 is upregulated on a wide range of cancer cells. Anti-PD-1
      and anti-PD-L1 monoclonal antibodies (mAbs), called immune checkpoint inhibitors
      (ICIs), have consequently been designed to restore T cell activity. Accumulating
      data are in favor of an association between PD-L1 expression in tumors and
      response to treatment. A PD-L1 expression is present in 30% to 50% of digestive
      cancers. Multiple anti-PD-1 (nivolumab, pembrolizumab) and anti-PD-L1 mAbs
      (MPDL3280A, Medi4736) are under evaluation in digestive cancers. Preliminary
      results in metastatic gastric cancer with pembrolizumab are highly promising and
      phase II will start soon. In metastatic colorectal cancer (CRC), a phase III
      trial of MPDL3280A as maintenance therapy will shortly be initiated. Trials are
      also ongoing in metastatic CRC with high immune T cell infiltration (i.e.,
      microsatellite instability). Major challenges are ahead in order to determine
      how, when and for which patients we should use these ICIs. New radiologic
      criteria to evaluate tumor response to ICIs are awaiting prospective validation.
      The optimal therapeutic sequence and association with cytotoxic chemotherapy
      needs to be established. Finally, biomarker identification will be crucial to
      selection of patients likely to benefit from ICIs. 

PMID- 26306142
TI  - Neoadjuvant or adjuvant therapy for gastric cancer.
AB  - Currently, there is no international consensus on the best treatment regimen for
      patients with advanced resectable gastric carcinoma. In the United States, where
      a limited lymph-node dissection is frequently performed, adjuvant
      chemoradiotherapy after surgery is the standard treatment. In Europe, intensified
      perioperative chemotherapy is commonly administered. In Japan and South Korea,
      postoperative S-1-based adjuvant chemotherapy after surgery with D2 lymph-node
      dissection is the standard treatment. Several ongoing trials are currently
      evaluating the optimal sequence of chemotherapy, radiotherapy, and surgery, as
      well as the place of targeted therapeutic agents in the treatment of advanced
      gastric carcinoma. 

PMID- 26306143
TI  - Inflammation-based factors and prognosis in patients with colorectal cancer.
AB  - Several parameters for predicting survival in patients with colorectal cancer
      have been identified, including the performance status, age, gender and tumor
      node-metastasis (TNM) stage. Although the TNM stage is important and useful for
      predicting the prognosis and determining the appropriate treatment, it is well
      known that the survival time varies widely, even in patients with the same stage
      of disease. Therefore, the identification of new parameters capable of more
      precisely predicting patient survival is needed to help select the optimal
      treatment, especially in patients in the advanced stage of disease. Although the
      TNM stage reflects the tumor characteristics, cancer progression and survival are
      not determined solely based on the local characteristics of the tumor, but also
      the host systemic immune/inflammatory response. Therefore, using a combination of
      parameters that reflect both tumor characteristics and the host systemic
      inflammatory status is thought to be important for accurately predicting patient
      survival. 

PMID- 26306144
TI  - Gastric carcinoma originating from the heterotopic submucosal gastric gland
      treated by laparoscopy and endoscopy cooperative surgery.
AB  - Gastric carcinoma is derived from epithelial cells in the gastric mucosa. We
      reported an extremely rare case of submucosal gastric carcinoma originating from
      the heterotopic submucosal gastric gland (HSG) that was safely diagnosed by
      laparoscopy and endoscopy cooperative surgery (LECS). A 66-year-old man underwent
      gastrointestinal endoscopy, which detected a submucosal tumor (SMT) of 1.5 cm in
      diameter on the lesser-anterior wall of the upper gastric body. The tumor could
      not be diagnosed histologically, even by endoscopic ultrasound-guided fine-needle
      aspiration biopsy. Local resection by LECS was performed to confirm a diagnosis.
      Pathologically, the tumor was an intra-submucosal well differentiated
      adenocarcinoma invading 5000 MUm into the submucosal layer. The resected tumor
      had negative lateral and vertical margins. Based on the Japanese treatment
      guidelines, additional laparoscopic proximal gastrectomy was curatively
      performed. LECS is a less invasive and safer approach for the diagnosis of SMT,
      even in submucosal gastric carcinoma originating from the HSG. 

PMID- 26306146
TI  - The Importance of Ethics in Medical Biotechnology.

PMID- 26306145
TI  - Esophageal granular cell tumors: Case report and literature review.
AB  - We reported 5 cases of granular cell tumors (GCTs) of esophagus and reviewed the
      literature. There were 4 females and 1 male with a median age of 43 years and an
      average age of 44 years. All of the cases had solitary tumors. Tumor size was 0.4
      2.5 cm in diameter. Gastroscopy revealed that 2 cases were located in the middle
      esophagus, 1 case in the upper esophagus, and 2 cases in the distal one. Five
      cases displayed gray-white, pink, yellow mucosal uplifts of esophagus, 3 cases
      had smooth surface, 1 case was slightly concave, and the biggest tumor had
      erosion. Tumor cells were large and polygonal with rich granular and eosinophilic
      cytoplasm, and small oval nuclei. Cells were arranged in nest or aciniform.
      Immunohistochemistry and histochemistry staining showed S-100+, neuron specific
      enolase+, Vim+, CD68+, smooth muscle actin-, Des-, CK-, CD117-, CD34-, Ki67-or <=
      5%+. Periodic acid-Schiff reaction and epithelial membrane antigen were both
      weakly positive. GCTs of esophagus are rare and most of the cases have good
      prognosis. 

PMID- 26306147
TI  - The Immunosuppressive Activity of Amniotic Membrane Mesenchymal Stem Cells on T
      Lymphocytes.
AB  - BACKGROUND: Mesenchymal Stem Cells (MSCs) are isolated from different sources
      like placenta. The placenta and its membranes like Amniotic Membrane (AM) are
      readily available and easy to work with. There is only limited knowledge on the
      immunomodulatory properties of human Amniotic Membrane-derived Mesenchymal Stem
      Cells (hAM-MSCs). The aim of this study was to survey the suppressive activity of
      hAM-MSCs on T lymphocytes in vitro. METHODS: Human AMs were obtained after
      caesarean section births from healthy women. After enzymatic digestion, cells
      were cultured and hAM-MSCs were obtained. In addition, human T lymphocytes were
      isolated and co-cultured with hAM-MSCs for 72 hr in the presence or absence of
      phytohemagglutinin (PHA). Subsequently, proliferation of T cells was analyzed
      using BrdU and subsequently flow cytometry technique. Besides, the production of
      IL-4 and IFN-gamma was examined by ELISA method. Additionally, the expression of
      activation markers (CD38, HLA-DR) was studied on T lymphocytes by flow cytometry
      technique. RESULTS: It was revealed that hAM-MSCs could significantly suppress
      the proliferation of T lymphocytes (p<=0.01) and significantly decrease the
      production of IFN-gamma by T cells (p<0.05). hAM-MSCs also down regulated the
      expression of activation markers on the surface of T lymphocytes, CD38 and HLA
      DR. The difference was significant between the case and control samples (p<0.05).
      All the comparisons were carried out between the case (Tcell+PHA+hAM-MSCs) and
      control (Tcell+PHA) groups. CONCLUSION: In conclusion, hAM-MSCs could inhibit the
      (mitogen-activated) T cells even in the absence of blood monocytes. Besides, hAM
      MSCs-mediated inhibition of T lymphocytes was combined with down regulation of
      activation markers.

PMID- 26306148
TI  - High Prevalence of Y Chromosome Partial Microdeletions in Overweight Men.
AB  - BACKGROUND: Microdeletions of the Y chromosome are one of the most frequent
      genetic causes of spermatogenic failure in infertile men. But their role in
      gaining weight is unclear. The present study investigated the possible
      association of these partial microdeletions and obesity. METHODS: In a case
      control study, 180 males were selected. The prevalence of microdeletions was
      assessed using PCR in AZFc area of Y chromosome and statistical analysis was done
      using the Fisher exact test and Pearson correlation. RESULTS: In our study,
      inverse relationship was observed between body mass index and testosterone level
      (p-value: 0.005). Fisher exact tests showed that there was a significant
      association between gr/gr mutation and BMI (p-value: 0.044). CONCLUSION: Our
      study revealed that Y chromosome microdeletions are more common in obese men.
      Furthermore, microdeletions such as gr/gr, which were observed in normal men,
      could cause decreased testosterone level. So, they may contribute to gaining
      weight.

PMID- 26306149
TI  - Expression of Recombinant Human Insulin-like Growth Factor Type 1 (rhIGF-1) in
      Escherichia coli.
AB  - BACKGROUND: Human insulin-like growth factor type 1 (hIGF-1) is a protein
      consisting of 70 amino acids (MW=7.6 kDa) and mainly synthesized by liver.
      Mecasermin (Trade name INCRELEX) is the synthetic form of the protein which is
      used as an effective treatment for particular disorders such as short stature,
      type 1 and 2 diabetes, and wound healing. Current study was aimed to investigate
      the expression of human insulin-like growth factor type1 in Escherichia coli (E.
      coli) BL21 (DE3) expression system in order to produce an active recombinant form
      of the protein. METHODS: For the purpose of the study, firstly codon optimization
      was done for hIGF-1 gene, using bioinformatics databases. Then, the gene was
      synthesized and inserted in pET-24a vector by a cutting strategy included NdeI
      and BamHI-HF enzymes. In the next step, gene was run in agarose gel and purified.
      The constructed expression cassette was transformed into E. coli BL21 (DE3) cells
      through CaCl 2 heat shock method. Identification and confirmation of the
      transformed colonies were performed using screening PCR method. Synthesis of hIGF
      1 was induced by IPTG. The expression in induced strains was analyzed by SDS-PAGE
      and western blotting techniques. Confirmation of cloning and IGF-1 expression
      cassette was carried out through genetic engineering procedures. RESULTS:
      Analysis of transformed E. coli strain with SDS-PAGE and western blotting
      techniques confirmed that gene was expressed in host cells. Molecular weight of
      the expressed protein was estimated to be 7.6 kDa. CONCLUSION: hIGF-1 expression
      cassette for cloning and expression in E. coli was designed and the protein of
      interest was successfully induced and identified. In addition, E. coli BL21 (DE3)
      can be used as a suitable host for production of recombinant hIGF-1 and this
      technology has a potential to be localized.

PMID- 26306150
TI  - Retinoic Acid as the Stimulating Factor for Differentiation of Wharton's Jelly
      Mesenchymal Stem Cells into Hepatocyte-like Cells.
AB  - BACKGROUND: Wharton's Jelly-Mesenchymal Stem Cells (WJ-MSCs) are pluripotent
      cells with differentiation capability into most cell lineages. The aim of the
      current work was to examine the role of Retinoic Acid (RA) in differentiation
      process of these cells into hepatocyte-like cells and determine the morphological
      and functional patterns. METHODS: Human WJ-MSCs were extracted, cultured and
      expanded; after approximately 95% of confluence, the cells were treated with
      hepatogenic media containing RA. The cells were subsequently analyzed for
      morphological changes, glycogen storage, albumin production, and specific gene
      expression. RESULTS: WJ-MSCs expressed high levels of CD90 (93.6%) and CD105
      (90.7%), but low levels of CD34 (0.3%) and CD45 (0.8%). Albumin production had
      significant difference in the two groups (p<=0.05). The data showed specific
      characteristics in favor of considering the differentiated cells as hepatocyte
      like cells such as obtaining morphologic, functional, and alphaFP and HNF1-alpha
      expression patterns which in turn were higher in cells exposed to RA. CONCLUSION:
      Based on the data of present study, RA is an effective molecule in inducing
      differentiation of WJ-MSCs into hepatocyte-like cells; therefore, it may be
      considered as a promising factor for targeting therapy of liver disorders.

PMID- 26306151
TI  - Inhibition of Coenzyme Qs Accumulation in Engineered Escherichia coli by High
      Concentration of Farnesyl Diphosphate.
AB  - BACKGROUND: Coenzyme Q 10 (CoQ 10 ) is an isoprenoid component used widely in
      nutraceutical industries. Farnesyl diphosphate synthase (FPPS) is a responsible
      enzyme for biosynthesis of farnesyl diphosphate (FPP), a key precursor for CoQs
      production. This research involved investigating the effect of FPPS over
      expression on CoQs production in engineered CoQ 10 -producing Escherichia coli
      (E. coli). METHODS: Two CoQ 10 -producing strains, as referred to E. coli Ba and
      E. coli Br, were transformed by the encoding gene for FPPS (ispA) under the
      control of either the trc or P BAD promoters. RESULTS: Over-expression of ispA
      under the control of P BAD promoter led to a relative increase in CoQ 10
      production only in recombinant E. coli Br although induction by arabinose
      resulted in partial reduction of CoQ 10 production in both recombinant E. coli Ba
      and E. coli Br strains. Over-expression of ispA under the control of stronger trc
      promoter, however, led to a severe decrease in CoQ 10 production in both
      recombinant E. coli Ba and E. coli Br strains, as reflected by reductions from
      629+/-40 to 30+/-13 and 564+/-28 to 80+/-14 MUg/g Dried Cell Weight (DCW),
      respectively. The results showed high level of FPP reduces endogenous CoQ 8
      production as well and that CoQs are produced in a complimentary manner, as the
      increase in production of one decreases the production of the other. CONCLUSION:
      The reduction in CoQ 10 production can be a result of Dds inhibition by high FPP
      concentration. Therefore, more effort is needed to verify the role of
      intermediate metabolite concentration and to optimize production of CoQ 10 .

PMID- 26306152
TI  - In silico Evaluation of Nonsynonymous Single Nucleotide Polymorphisms in the
      ADIPOQ Gene Associated with Diabetes, Obesity, and Inflammation.
AB  - BACKGROUND: The human ADIPOQ gene encodes adiponectin protein hormone, which is
      involved in regulating glucose levels as well as fatty acid breakdown. It is
      exclusively produced by adipose tissue and abundantly present in the circulation,
      with concentration of around 0.01% of total serum proteins, with important effect
      on metabolism. METHODS: Most deleterious nonsynonymous single nucleotide
      polymorphisms in the coding region of the ADIPOQ gene were investigated using SNP
      databases, and detected nonsynonymous variants were analyzed in silico from the
      standpoint of relevant protein function and stability by using SIFT, PolyPhen-2,
      PROVEAN and MUpro, I-Mutant2.0 tools, respectively. RESULT: A total of 58
      nonsynonymous SNPs consisting of 55 missense variations, 3 nonsense variations
      were found in the ADIPOQ gene. Next, 14 of the 55 missense variants were
      predicted to be damaging or deleterious by three different software programs
      (PolyPhen-2, SIFT, and PROVEAN), and 38 of them were predicted to be less stable
      (I-Mutant 2.0 and MUpro software). Totally, 10 variants out of 55 missense
      variants were predicted to be both deleterious and reduce protein stability.
      Additionally, 3 nonsense variants were predicted to produce a truncated ADIPOQ
      protein. RMSD and total energy were calculated for 4 nsSNPs out of 10 nsSNPs
      which were both deleterious and showed a decrease in protein stability.
      CONCLUSION: rs144526209 has high root-mean-square deviation (RMSD) and lower
      total energy value compared to the native modeled structure. It was concluded
      that this nsSNP, potentially functional and polymorphic in the ADIPOQ gene, might
      be associated with diabetes, obesity, and inflammation.

PMID- 26306154
TI  - Regenerative Medicine in Organ and Tissue Transplantation: Shortly and
      Practically Achievable?
AB  - Since the beginning of organ/tissue transplantation, the therapeutic modality of
      choice in end-stage organ failure, organ shortage has been the main problem in
      transplantation medicine. Given the so far unsolved obstacle, all hope-raising
      procedures to possibly tackle this long-lasting problem can draw attentions. In
      this context, "regenerative medicine" sounds to be more promising compared to
      other approaches. To consider the huge impact of hematopoietic stem cell
      transplantation on the treatment of some congenital or acquired hematological or
      metabolic disorders and some advances to produce tissue engineered materials on
      one hand, and to take all aspects of this emerging and costly interdisciplinary
      field of research into consideration, on the other hand, inevitably makes this
      reality unchanged, in particular in countries with low or middle income, that
      allograft (from deceased or living donors) will remain for years as the
      irreplaceable source of organ transplantation. 

PMID- 26306153
TI  - An Association Study on IL16 Gene Polymorphisms with the Risk of Sporadic
      Alzheimer's Disease.
AB  - BACKGROUND: Interleukin-16 (IL-16) is an important regulator of T cell activation
      and was reported to act as a chemoattractant agent. There are evidences that IL16
      can control the neuroinflammatory processes in Alzheimer's Disease (AD). This
      study was performed to investigate the role or association of IL16 polymorphisms,
      rs11556218 and rs4778889 with the risk of late-onset Alzheimer's disease (LOAD)
      in Iranian population. METHODS: Totally, 148 AD patients and 137 nondemented and
      age-matched subjects were recruited in this study. Genotyping of rs11556218 T/G
      and rs4778889 T/C polymorphisms was performed by PCR-RFLP method using the NdeI
      and AhdI restriction enzymes, respectively. RESULTS: Statistical analysis of
      rs11556218 genotypes showed a protective effect against AD in the heterozygote
      genotype (p=0.001, OR=0.16) as well as rs4778889 (p=0.001, OR=0.23). Frequency of
      rs11556218 allele T was higher in controls than patients (p=0.001, OR=0.32).
      However, there was no significant difference in the frequencies of rs4778889
      alleles between the AD patients and controls. CONCLUSION: Our results indicate
      that the rs11556218 and rs4778889 polymorphisms have a protective role in the
      development of sporadic AD in Iranian population.

PMID- 26306155
TI  - Lower Oncogenic Potential of Human Mesenchymal Stem Cells Derived from Cord Blood
      Compared to Induced Pluripotent Stem Cells.
AB  - BACKGROUND: In regenerative medicine, use of each of the mesenchymal stem cells
      derived from bone marrow, cord blood, and adipose tissue, has several cons and
      pros. Mesenchymal stem cells derived from cord blood have been considered the
      best source for precursor transplantation. Direct reprogramming of a somatic cell
      into induced pluripotent stem cells by over-expression of 6 transcription factors
      Oct4, Sox2, Klf4, lin28, Nanog, and c-Myc has great potential for regenerative
      medicine, eliminating the ethical issues of embryonic stem cells and the
      rejection problems of using non-autologous cells. OBJECTIVE: To compare
      reprogramming and pluripotent markers OCT4, Sox-2, c-Myc, Klf4, Nanog, and lin28
      in mesenchymal stem cells derived from cord blood and induced pluripotent stem
      cells. METHODS: We analyzed the expression level of OCT4, Sox-2, c-Myc, Klf4,
      Nanog and lin28 genes in human mesenchymal stem cells derived from cord blood and
      induced pluripotent stem cells by cell culture and RT-PCR. RESULTS: The
      expression level of pluripotent genes OCT4 and Sox-2, Nanog and lin28 in
      mesenchymal stem cells derived from cord blood were significantly higher than
      those in induced pluripotent stem cells. In contrast to OCT-4A and Sox-2, Nanog
      and lin28, the expression level of oncogenic factors c-Myc and Klf4 were
      significantly higher in induced pluripotent stem cells than in mesenchymal stem
      cells derived from cord blood. CONCLUSION: It could be concluded that mesenchymal
      stem cells derived from human cord blood have lower oncogenic potential compared
      to induced pluripotent stem cells.

PMID- 26306156
TI  - ICU Nurses' Knowledge, Attitude, and Practice Towards their Role in the Organ
      Donation Process from Brain-Dead Patients and Factors Influencing it in Iran.
AB  - BACKGROUND: Nowadays, ICU nurses play a significant role in the care of brain
      dead patients and their families. Therefore, their knowledge, attitude and
      practice towards this issue are extremely important to the success of organ
      donation. OBJECTIVE: To assess ICU nurses' knowledge, attitude and practice
      towards their role in the organ donation process from brain-dead patients and
      factors influencing it in Iran. METHODS: In a cross-sectional analytical study,
      90 ICU nurses working in Ghaem and Emam Reza Hospitals affiliated to Mashhad
      University of Medical Sciences were selected through a stratified random
      sampling. Data were collected from the participants by a questionnaire included
      demographic information, and factors influencing the nurses knowledge, attitude,
      and practice towards their roles in the organ donation process. RESULTS: 90
      nurses participated in this study. 70% of the research subjects had spoken with
      their own families about organ donation; 20% had organ donation cards. The mean+/
      SD score of nurses' knowledge was 49.13+/-9.6, attitude 21.49+/-14.32, and
      practice was 3.66+/-6.04. 80% of nurses had a mean knowledge about their roles in
      the organ donation process; 82% agreed with their roles in this process, and 97%
      showed weak practice in this regard. CONCLUSION: Nurses did not have adequate
      knowledge, attitude, and practice towards their role in organ donation process.
      It is suggested to include nursing courses on the organ donation process and
      organ transplantation as well as educational programs to acquaint nurses with
      their roles in the organ donation process.

PMID- 26306157
TI  - Kidney Allograft Stone after Kidney Transplantation and its Association with
      Graft Survival.
AB  - BACKGROUND: It is said that renal transplantation lithiasis is rare. However,
      literature has some different frequencies in this field and most of the studies
      related to this issue are case reports. Also the exact effect of this
      complication on the graft survival rate is not clear. OBJECTIVES: To determine
      the prevalence of nephrolithiasis among kidney transplant recipients and evaluate
      its association with the graft survival. METHODS: We conducted a retrospective
      study to determine the prevalence of renal stone among 574 kidney transplant
      patients aged >=18 years who had undergone renal transplantation in Baqiyatallah
      Transplant Center between 1990 and 2010. Cox regression analysis was used to
      determine the effect of renal stone on the graft survival. RESULTS: The mean+/-SD
      follow-up time was 55+/-53 months. Kidney stones were diagnosed in 31 (4.4%) of
      all 574 kidney transplants studied. Cox regression analysis revealed that
      nephrolithiasis after transplantation had no significant effects on the survival
      of the transplanted kidney (OR 1.04, CI: 0.708-1.54). CONCLUSION: For the first
      time, we showed that nephrolithiasis in recipients does not have a significant
      effect on the transplant survival.

PMID- 26306158
TI  - Comparison of Cox's Regression Model and Parametric Models in Evaluating the
      Prognostic Factors for Survival after Liver Transplantation in Shiraz during 2000
      2012.
AB  - BACKGROUND: Identification of the prognostic factors for survival in patients
      with liver transplantation is challengeable. Various methods of survival analysis
      have provided different, sometimes contradictory, results from the same data.
      OBJECTIVE: To compare Cox's regression model with parametric models for
      determining the independent factors for predicting adults' and pediatrics'
      survival after liver transplantation. METHOD: This study was conducted on 183
      pediatric patients and 346 adults underwent liver transplantation in Namazi
      Hospital, Shiraz, southern Iran. The study population included all patients
      undergoing liver transplantation from 2000 to 2012. The prognostic factors sex,
      age, Child class, initial diagnosis of the liver disease, PELD/MELD score, and
      pre-operative laboratory markers were selected for survival analysis. RESULT:
      Among 529 patients, 346 (64.5%) were adult and 183 (34.6%) were pediatric cases.
      Overall, the lognormal distribution was the best-fitting model for adult and
      pediatric patients. Age in adults (HR=1.16, p<0.05) and weight (HR=2.68, p<0.01)
      and Child class B (HR=2.12, p<0.05) in pediatric patients were the most important
      factors for prediction of survival after liver transplantation. Adult patients
      younger than the mean age and pediatric patients weighing above the mean and
      Child class A (compared to those with classes B or C) had better survival.
      CONCLUSION: Parametric regression model is a good alternative for the Cox's
      regression model.

PMID- 26306159
TI  - Progressive Multifocal Leukoencephalopathy after Three Consecutive Liver
      Transplantations.
AB  - Progressive multifocal leukoencephalopathy (PML) is a lytic infection of the
      central nervous system caused by the reactivation of John Cunningham Virus (JCV)
      in severely immunosuppressed patients. Occurrence of PML after solid organ
      transplantations, especially after liver transplantation, is rare. If a patient
      has poor prognostic factors such as atypical radiological involvements or high
      viral load in cerebrospinal fluid (CSF), overall survival rates could be poor.
      Herein, we report on a patients who underwent liver transplantation three times
      and developed PML with unexpected radiological findings; he was also positive for
      JCV DNA with a high viral load. Although there are limited data about efficacy of
      cytarabine against JCV, it was given to the patient for five days. Despite the
      initiation of cytarabine and complete cessation of the immunosuppressive therapy,
      we lost the patient, unfortunately. 

PMID- 26306160
TI  - Combined Liver-Kidney Transplantation for Hepatorenal Syndrome.
AB  - Among various complications of end-stage liver disease, hepatorenal syndrome has
      the highest mortality. Patients with both end-stage liver disease and end-stage
      renal disease are candidates for combined liver-kidney transplantation. However,
      patients with cirrhosis with decompensation presenting in the form of hepatorenal
      syndrome, are also likely candidates for the procedure. Herein, we present a
      patient who underwent combined liver-kidney transplantation for hepatorenal
      syndrome. 

PMID- 26306161
TI  - Collecting psychosocial self-report data in oral health research: impact of
      literacy level and computerised administration.
AB  - OBJECTIVES: In oral and other health research, participant literacy levels may
      impact the quality of data obtained through self-report (e.g., degree of data
      missingness). This study addressed whether computerized administration of a
      battery of psychosocial instruments used in an oral health disparities research
      protocol yielded more complete data than paper-and-pencil administration and
      aimed to determine the role of general literacy in differences in data
      missingness between administration types. DESIGN: Oral health data were obtained
      from 1,652 adolescent and adult participants who were administered a large
      questionnaire battery via either paper-and-pencil or tablet personal computer.
      Number of unanswered items for each participant was compared across
      administration mode. For a subset of 171 participants who were randomized to one
      of the administration modes, general literacy and satisfaction with the
      questionnaire experience also were assessed. RESULTS: Participants assigned to
      complete the oral health questionnaire battery via tablet PC were significantly
      more likely than those assigned to the paper-and-pencil condition to have missing
      data for at least one item (p < .001); however, for participants who had at least
      one missing item, paper-and-pencil administration was associated with a greater
      number of items missed than was tablet PC administration (p < .001). Across
      administration modes, participants with higher literacy level completed the
      questionnaire battery more rapidly than their lower literacy counterparts (p <
      .001). Participant satisfaction was similar for both modes of questionnaire
      administration (p >= .29). CONCLUSIONS: These results suggest that a certain type
      of data missingness may be decreased through the use of a tablet computer for
      questionnaire administration.

PMID- 26306162
TI  - Marketing or strategy? Defining the best approach to expand the anesthesiology
      workforce in Israel.
AB  - There is a chronic shortage of anesthesiologists in Israel. The study by Cohen et
      al. suggests that a marketing campaign may be one method of addressing this
      shortage. This commentary argues for a more comprehensive strategy based on the
      US experience. This would not only involve marketing as suggested by Cohen et al.
      but would also involve a fundamental change in the Israel anesthesia care model,
      as well as providing substantial financial incentives to young physicians. We
      believe that a combination of these approaches will help to alleviate the
      shortage of anesthesia providers in Israel. Creating a new class of physician
      extenders, namely, anesthesiologist assistants, would also provide an employment
      pathway for the skilled medical technicians trained by the Israel Defense Forces,
      and other non-physicians with an interest in anesthesiology. 

PMID- 26306163
TI  - Reconciling actual and perceived rates of predation by domestic cats.
AB  - The predation of wildlife by domestic cats (Felis catus) is a complex problem:
      Cats are popular companion animals in modern society but are also acknowledged
      predators of birds, herpetofauna, invertebrates, and small mammals. A
      comprehensive understanding of this conservation issue demands an understanding
      of both the ecological consequence of owning a domestic cat and the attitudes of
      cat owners. Here, we determine whether cat owners are aware of the predatory
      behavior of their cats, using data collected from 86 cats in two UK villages. We
      examine whether the amount of prey their cat returns influences the attitudes of
      45 cat owners toward the broader issue of domestic cat predation. We also
      contribute to the wider understanding of physiological, spatial, and behavioral
      drivers of prey returns among cats. We find an association between actual prey
      returns and owner predictions at the coarse scale of predatory/nonpredatory
      behavior, but no correlation between the observed and predicted prey-return rates
      among predatory cats. Cat owners generally disagreed with the statement that cats
      are harmful to wildlife, and disfavored all mitigation options apart from
      neutering. These attitudes were uncorrelated with the predatory behavior of their
      cats. Cat owners failed to perceive the magnitude of their cats' impacts on
      wildlife and were not influenced by ecological information. Management options
      for the mitigation of cat predation appear unlikely to work if they focus on
      "predation awareness" campaigns or restrictions of cat freedom. 

PMID- 26306164
TI  - Sexual shape dimorphism accelerated by male-male competition, but not prevented
      by sex-indiscriminate parental care in dung beetles (Scarabaeidae).
AB  - Dimorphic sexual differences in shape and body size are called sexual dimorphism
      and sexual size dimorphism, respectively. The degrees of both dimorphisms are
      considered to increase with sexual selection, represented by male-male
      competition. However, the degrees of the two dimorphisms often differ within a
      species. In some dung beetles, typical sexual shape dimorphisms are seen in male
      horns and other exaggerated traits, although sexual size dimorphism looks rare.
      We hypothesized that the evolution of this sexual shape dimorphism without sexual
      size dimorphism is caused by male-male competition and their crucial and sex
      indiscriminate provisioning behaviors, in which parents provide the equivalent
      size of brood ball with each of both sons and daughters indiscriminately. As a
      result of individual-based model simulations, we show that parents evolve to
      provide each of sons and daughters with the optimal amount of resource for a son
      when parents do not distinguish the sex of offspring and males compete for mates.
      This result explains why crucial and sex-indiscriminate parental provisioning
      does not prevent the evolution of sexual shape dimorphism. The model result was
      supported by empirical data of Scarabaeidae beetles. In some dung beetles, sexual
      size dimorphism is absent, compared with significant sexual size dimorphism in
      other horned beetles, although both groups exhibit similar degrees of sexual
      shape dimorphism in male horns and other exaggerated traits. 

PMID- 26306165
TI  - Spatial interactions between sympatric carnivores: asymmetric avoidance of an
      intraguild predator.
AB  - Interactions between intraguild species that act as both competitors and predator
      prey can be especially complex. We studied patterns of space use by the black
      footed ferret (Mustela nigripes), a prairie dog (Cynomys spp.) specialist, and
      the American badger (Taxidea taxus), a larger generalist carnivore that competes
      for prairie dogs and is known to kill ferrets. We expected that ferrets would
      spatially avoid badgers because of the risk of predation, that these patterns of
      avoidance might differ between sexes and age classes, and that the availability
      of food and space might influence these relationships. We used location data from
      60 ferrets and 15 badgers to model the influence of extrinsic factors (prairie
      dog density and colony size) and intrinsic factors (sex, age) on patterns of
      space use by ferrets in relation to space use by different sex and age categories
      of badgers. We documented asymmetric patterns of avoidance of badgers by ferrets
      based on the sex of both species. Female ferrets avoided adult female badgers,
      but not male badgers, and male ferrets exhibited less avoidance than female
      ferrets. Additionally, avoidance decreased with increasing densities of prairie
      dogs. We suggest that intersexual differences in space use by badgers create
      varying distributions of predation risk that are perceived by the smaller
      carnivore (ferrets) and that females respond more sensitively than males to that
      risk. This work advances understanding about how competing species coexist and
      suggests that including information on both intrinsic and extrinsic factors might
      improve our understanding of behavioral interactions between sympatric species. 

PMID- 26306166
TI  - Variation in signal-preference genetic correlations in Enchenopa treehoppers
      (Hemiptera: Membracidae).
AB  - Fisherian selection is a within-population process that promotes signal
      preference coevolution and speciation due to signal-preference genetic
      correlations. The importance of the contribution of Fisherian selection to
      speciation depends in part on the answer to two outstanding questions: What
      explains differences in the strength of signal-preference genetic correlations?
      And, how does the magnitude of within-species signal-preference covariation
      compare to species differences in signals and preferences? To address these
      questions, we tested for signal-preference genetic correlations in two members of
      the Enchenopa binotata complex, a clade of plant-feeding insects wherein
      speciation involves the colonization of novel host plants and signal-preference
      divergence. We used a full-sibling, split-family rearing experiment to estimate
      genetic correlations and to analyze the underlying patterns of variation in
      signals and preferences. Genetic correlations were weak or zero, but exploration
      of the underlying patterns of variation in signals and preferences revealed some
      full-sib families that varied by as much as 50% of the distance between similar
      species in the E. binotata complex. This result was stronger in the species that
      showed greater amounts of genetic variation in signals and preferences. We argue
      that some forms of weak signal-preference genetic correlation may have important
      evolutionary consequences. 

PMID- 26306167
TI  - Related male Drosophila melanogaster reared together as larvae fight less and
      sire longer lived daughters.
AB  - Competition over access to reproductive opportunities can lead males to harm
      females. However, recent work has shown that, in Drosophila melanogaster, male
      competition and male harm of females are both reduced under conditions simulating
      male-specific population viscosity (i.e., in groups where males are related and
      reared with each other as larvae). Here, we seek to replicate these findings and
      investigate whether male population viscosity can have repercussions for the
      fitness of offspring in the next generation. We show that groups of unrelated
      unfamiliar (i.e., unrelated individuals raised apart) males fight more intensely
      than groups of related-familiar males (i.e., full siblings raised together as
      larvae), supporting previous findings, and that exposure to a female is required
      to trigger these differential patterns of male-male competition. Importantly, we
      show that differences in male-male competition can be associated with
      transgenerational effects: the daughters of females exposed to unrelated
      unfamiliar males suffered higher mortality than the daughters of females exposed
      to related-familiar males. Collectively, these results suggest that population
      structure (i.e., variation in the relatedness and/or larval familiarity of local
      male groups) can modulate male-male competition with important transgenerational
      consequences. 

PMID- 26306168
TI  - Phylogeography of Pogonomyrmex barbatus and P. rugosus harvester ants with
      genetic and environmental caste determination.
AB  - We present a phylogeographic study of at least six reproductively isolated
      lineages of new world harvester ants within the Pogonomyrmex barbatus and P.
      rugosus species group. The genetic and geographic relationships within this clade
      are complex: Four of the identified lineages show genetic caste determination
      (GCD) and are divided into two pairs. Each pair has evolved under a mutualistic
      system that necessitates sympatry. These paired lineages are dependent upon one
      another because their GCD requires interlineage matings for the production of F1
      hybrid workers, and intralineage matings are required to produce queens. This GCD
      system maintains genetic isolation among these interdependent lineages, while
      simultaneously requiring co-expansion and emigration as their distributions have
      changed over time. It has also been demonstrated that three of these four GCD
      lineages have undergone historical hybridization, but the narrower sampling range
      of previous studies has left questions on the hybrid parentage, breadth, and age
      of these groups. Thus, reconstructing the phylogenetic and geographic history of
      this group allows us to evaluate past insights and hypotheses and to plan future
      inquiries in a more complete historical biogeographic context. Using
      mitochondrial DNA sequences sampled across most of the morphospecies' ranges in
      the U.S.A. and Mexico, we conducted a detailed phylogeographic study. Remarkably,
      our results indicate that one of the GCD lineage pairs has experienced a dramatic
      range expansion, despite the genetic load and fitness costs of the GCD system.
      Our analyses also reveal a complex pattern of vicariance and dispersal in
      Pogonomyrmex harvester ants that is largely concordant with models of late
      Miocene, Pliocene, and Pleistocene range shifts among various arid-adapted taxa
      in North America. 

PMID- 26306169
TI  - Two eggs, two different constraints: a potential explanation for the puzzling
      intraclutch egg size dimorphism in Eudyptes penguins.
AB  - Phenotypic plasticity and phenotypic stability are major components of the
      adaptive evolution of organisms to environmental variation. The invariant two-egg
      clutch size of Eudyptes penguins has recently been proposed to be a unique
      example of a maladaptive phenotypic stability, while their egg mass is a plastic
      trait. We tested whether this phenotypic plasticity during reproduction might
      result from constraints imposed by migration (migratory carry-over effect) and
      breeding (due to the depletion of female body reserves). For the first time, we
      examined whether these constraints differ between eggs within clutches and
      between egg components (yolk and albumen). The interval between colony return and
      clutch initiation positively influenced the yolk mass, the albumen mass, and the
      subsequent total egg mass of first-laid eggs. This time interval had only a
      slight negative influence on the yolk mass of second-laid eggs and no influence
      on their albumen and subsequent total masses. For both eggs, female body mass at
      laying positively influenced albumen and total egg masses. Female investment into
      the entire clutch was not related to the time in the colony before laying but
      increased with female body mass. These novel results suggest that the unique
      intraclutch egg size dimorphism exhibited in Eudyptes penguins, with first-laid
      eggs being consistently smaller than second-laid eggs, might be due to a
      combination of constraints: a migratory carry-over effect on the first-laid egg
      and a body reserve depletion effect on the second-laid egg. Both these
      constraints might explain why the timing of reproduction, especially egg
      formation, is narrow in migratory capital breeders. 

PMID- 26306170
TI  - Scaling nitrogen and carbon interactions: what are the consequences of biological
      buffering?
AB  - Understanding the consequences of elevated CO2 (eCO2; 800 ppm) on terrestrial
      ecosystems is a central theme in global change biology, but relatively little is
      known about how altered plant C and N metabolism influences higher levels of
      biological organization. Here, we investigate the consequences of C and N
      interactions by genetically modifying the N-assimilation pathway in Arabidopsis
      and initiating growth chamber and mesocosm competition studies at current CO2
      (cCO2; 400 ppm) and eCO2 over multiple generations. Using a suite of ecological,
      physiological, and molecular genomic tools, we show that a single-gene mutant of
      a key enzyme (nia2) elicited a highly orchestrated buffering response starting
      with a fivefold increase in the expression of a gene paralog (nia1) and a 63%
      increase in the expression of gene network module enriched for N-assimilation
      genes. The genetic perturbation reduced amino acids, protein, and TCA-cycle
      intermediate concentrations in the nia2 mutant compared to the wild-type, while
      eCO2 mainly increased carbohydrate concentrations. The mutant had reduced net
      photosynthetic rates due to a 27% decrease in carboxylation capacity and an 18%
      decrease in electron transport rates. The expression of these buffering
      mechanisms resulted in a penalty that negatively correlated with fitness and
      population dynamics yet showed only minor alterations in our estimates of
      population function, including total per unit area biomass, ground cover, and
      leaf area index. This study provides insight into the consequences of buffering
      mechanisms that occur post-genetic perturbations in the N pathway and the
      associated outcomes these buffering systems have on plant populations relative to
      eCO2. 

PMID- 26306171
TI  - Population substructure and space use of Foxe Basin polar bears.
AB  - Climate change has been identified as a major driver of habitat change,
      particularly for sea ice-dependent species such as the polar bear (Ursus
      maritimus). Population structure and space use of polar bears have been
      challenging to quantify because of their circumpolar distribution and tendency to
      range over large areas. Knowledge of movement patterns, home range, and habitat
      is needed for conservation and management. This is the first study to examine the
      spatial ecology of polar bears in the Foxe Basin management unit of Nunavut,
      Canada. Foxe Basin is in the mid-Arctic, part of the seasonal sea ice ecoregion
      and it is being negatively affected by climate change. Our objectives were to
      examine intrapopulation spatial structure, to determine movement patterns, and to
      consider how polar bear movements may respond to changing sea ice habitat
      conditions. Hierarchical and fuzzy cluster analyses were used to assess
      intrapopulation spatial structure of geographic position system satellite
      collared female polar bears. Seasonal and annual movement metrics (home range,
      movement rates, time on ice) and home-range fidelity (static and dynamic overlap)
      were compared to examine the influence of regional sea ice on movements. The
      polar bears were distributed in three spatial clusters, and there were
      differences in the movement metrics between clusters that may reflect sea ice
      habitat conditions. Within the clusters, bears moved independently of each other.
      Annual and seasonal home-range fidelity was observed, and the bears used two
      movement patterns: on-ice range residency and annual migration. We predict that
      home-range fidelity may decline as the spatial and temporal predictability of sea
      ice changes. These new findings also provide baseline information for managing
      and monitoring this polar bear population. 

PMID- 26306172
TI  - Molecular evidence for hybridization in Colias (Lepidoptera: Pieridae): are
      Colias hybrids really hybrids?
AB  - Gene flow and hybridization among species dramatically affect our understanding
      of the species as a biological unit, species relationships, and species
      adaptations. In North American Colias eurytheme and Colias eriphyle, there has
      been historical debate over the extent of hybridization occurring and the
      identity of phenotypically intermediate individuals as genetic hybrids. This
      study assesses the population structure of these two species to measure the
      extent of hybridization and the genetic identity of phenotypic intermediates as
      hybrids. Amplified fragment length polymorphism (AFLP) marker analysis was
      performed on 378 specimens collected from northern California and Nevada.
      Population structure was inferred using a Bayesian/Markov chain Monte Carlo
      method, which probabilistically assigns individuals to genetic clusters. Three
      genetic clusters provided the best fit for the data. C. eurytheme individuals
      were primarily assigned to two closely related clusters, and C. eriphyle
      individuals were mostly assigned to a third, more distantly related cluster.
      There appeared to be significant hybridization between the two species.
      Individuals of intermediate phenotype (putative hybrids) were found to be
      genetically indistinguishable from C. eriphyle, indicating that previous work
      based on the assumption that these intermediate forms are hybrids may warrant
      reconsideration. 

PMID- 26306173
TI  - Global Invader Impact Network (GIIN): toward standardized evaluation of the
      ecological impacts of invasive plants.
AB  - Terrestrial invasive plants are a global problem and are becoming ubiquitous
      components of most ecosystems. They are implicated in altering disturbance
      regimes, reducing biodiversity, and changing ecosystem function, sometimes in
      profound and irreversible ways. However, the ecological impacts of most invasive
      plants have not been studied experimentally, and most research to date focuses on
      few types of impacts, which can vary greatly among studies. Thus, our knowledge
      of existing ecological impacts ascribed to invasive plants is surprisingly
      limited in both breadth and depth. Our aim was to propose a standard methodology
      for quantifying baseline ecological impact that, in theory, is scalable to any
      terrestrial plant invader (e.g., annual grasses to trees) and any invaded system
      (e.g., grassland to forest). The Global Invader Impact Network (GIIN) is a
      coordinated distributed experiment composed of an observational and manipulative
      methodology. The protocol consists of a series of plots located in (1) an invaded
      area; (2) an adjacent removal treatment within the invaded area; and (3) a
      spatially separate uninvaded area thought to be similar to pre-invasion
      conditions of the invaded area. A standardized and inexpensive suite of
      community, soil, and ecosystem metrics are collected allowing broad comparisons
      among measurements, populations, and species. The method allows for one-time
      comparisons and for long-term monitoring enabling one to derive information about
      change due to invasion over time. Invader removal plots will also allow for
      quantification of legacy effects and their return rates, which will be monitored
      for several years. GIIN uses a nested hierarchical scale approach encompassing
      multiple sites, regions, and continents. Currently, GIIN has network members in
      six countries, with new members encouraged. To date, study species include
      representatives of annual and perennial grasses; annual and perennial forbs;
      shrubs; and trees. The goal of the GIIN framework is to create a standard yet
      flexible platform for understanding the ecological impacts of invasive plants,
      allowing both individual and synthetic analyses across a range of taxa and
      ecosystems. If broadly adopted, this standard approach will offer unique insight
      into the ecological impacts of invasive plants at local, regional, and global
      scales. 

PMID- 26306174
TI  - rBEFdata: documenting data exchange and analysis for a collaborative data
      management platform.
AB  - We are witnessing a growing gap separating primary research data from derived
      data products presented as knowledge in publications. Although journals today
      more often require the underlying data products used to derive the results as a
      prerequisite for a publication, the important link to the primary data is lost.
      However, documenting the postprocessing steps of data linking, the primary data
      with derived data products has the potential to increase the accuracy and the
      reproducibility of scientific findings significantly. Here, we introduce the
      rBEFdata R package as companion to the collaborative data management platform
      BEFdata. The R package provides programmatic access to features of the platform.
      It allows to search for data and integrates the search with external thesauri to
      improve the data discovery. It allows to download and import data and metadata
      into R for analysis. A batched download is available as well which works along a
      paper proposal mechanism implemented by BEFdata. This feature of BEFdata allows
      to group primary data and metadata and streamlines discussions and collaborations
      revolving around a certain research idea. The upload functionality of the R
      package in combination with the paper proposal mechanism of the portal allows to
      attach derived data products and scripts directly from R, thus addressing major
      aspects of documenting data postprocessing. We present the core features of the
      rBEFdata R package along an ecological analysis example and further discuss the
      potential of postprocessing documentation for data, linking primary data with
      derived data products and knowledge. 

PMID- 26306175
TI  - Relative impacts of environmental variation and evolutionary history on the
      nestedness and modularity of tree-herbivore networks.
AB  - Nestedness and modularity are measures of ecological networks whose causative
      effects are little understood. We analyzed antagonistic plant-herbivore bipartite
      networks using common gardens in two contrasting environments comprised of aspen
      trees with differing evolutionary histories of defence against herbivores. These
      networks were tightly connected owing to a high level of specialization of
      arthropod herbivores that spend a large proportion of the life cycle on aspen.
      The gardens were separated by ten degrees of latitude with resultant differences
      in abiotic conditions. We evaluated network metrics and reported similar
      connectance between gardens but greater numbers of links per species in the
      northern common garden. Interaction matrices revealed clear nestedness,
      indicating subsetting of the bipartite interactions into specialist divisions, in
      both the environmental and evolutionary aspen groups, although nestedness values
      were only significant in the northern garden. Variation in plant vulnerability,
      measured as the frequency of herbivore specialization in the aspen population,
      was significantly partitioned by environment (common garden) but not by
      evolutionary origin of the aspens. Significant values of modularity were observed
      in all network matrices. Trait-matching indicated that growth traits, leaf
      morphology, and phenolic metabolites affected modular structure in both the
      garden and evolutionary groups, whereas extra-floral nectaries had little
      influence. Further examination of module configuration revealed that plant
      vulnerability explained considerable variance in web structure. The contrasting
      conditions between the two gardens resulted in bottom-up effects of the
      environment, which most strongly influenced the overall network architecture,
      however, the aspen groups with dissimilar evolutionary history also showed
      contrasting degrees of nestedness and modularity. Our research therefore shows
      that, while evolution does affect the structure of aspen-herbivore bipartite
      networks, the role of environmental variations is a dominant constraint. 

PMID- 26306176
TI  - Seasonal effects on egg production and level of paternity in a natural population
      of a simultaneous hermaphrodite snail.
AB  - In a seasonal environment, the suitable time window for females to reproduce is
      restricted by both environmental conditions and the availability of males. In
      simultaneous hermaphrodites, which are female and male at the same time,
      selection on a trait that is solely beneficial for one sexual function cannot
      occur independently. Therefore, it is assumed that the optimal time window for
      reproduction is a compromise between the two sexual functions in simultaneous
      hermaphrodites, mediated by environmental conditions. We examined seasonal
      patterns of reproduction and the resulting paternity in a natural population of
      the simultaneously hermaphroditic land snail Arianta arbustorum. Adult and
      premature individuals (snails in a short protandric phase) were collected on four
      occasions over the entire active season. The snails were allowed to deposit eggs
      after which we assessed the level of paternity in their hatched offspring.
      Individuals mated throughout the reproductive season, whereas egg production -
      the major task of the female function - was restricted to the first half of the
      season. Snails collected in autumn were allowed to hibernate under laboratory
      conditions. As a result, we found that premature individuals began to mate late
      in the reproductive season, but did not start to produce eggs before emerging
      from hibernation. Our results demonstrate a temporal shift of reproductive
      activities; the egg production and oviposition occur mainly in the first half of
      the season, while sperm production and mating occur over the entire season. In
      subadult and adult snails, sperm obtained from several partners in the second
      part of the reproductive season are stored during hibernation for the
      fertilization of eggs in the successive years. These results extend our
      understanding of the influence of both natural and sexual selection on
      reproductive strategies in hermaphrodites. 

PMID- 26306177
TI  - High genetic diversity and geographic subdivision of three lance nematode species
      (Hoplolaimus spp.) in the United States.
AB  - Lance nematodes (Hoplolaimus spp.) feed on the roots of a wide range of plants,
      some of which are agronomic crops. Morphometric values of amphimictic lance
      nematode species overlap considerably, and useful morphological characters for
      their discrimination require high magnification and significant diagnostic time.
      Given their morphological similarity, these Hoplolaimus species provide an
      interesting model to investigate hidden diversity in crop agroecosystems. In this
      scenario, H. galeatus may have been over-reported and the related species that
      are morphologically similar could be more widespread in the United States that
      has been recognized thus far. The main objectives of this study were to delimit
      Hoplolaimus galeatus and morphologically similar species using morphology,
      phylogeny, and a barcoding approach, and to estimate the genetic diversity and
      population structure of the species found. Molecular analyses were performed
      using sequences of the cytochrome c oxidase subunit 1 (Cox1) and the internal
      transcribed spacer (ITS1) on 23 populations. Four morphospecies were identified:
      H. galeatus, H. magnistylus, H. concaudajuvencus, and H. stephanus, along with a
      currently undescribed species. Pronounced genetic structure correlated with
      geographic origin was found for all species, except for H. galeatus. Hoplolaimus
      galeatus also exhibited low genetic diversity and the shortest genetic distances
      among populations. In contrast, H. stephanus, the species with the fewest reports
      from agricultural soils, was the most common and diverse species found. Results
      of this project may lead to better delimitation of lance nematode species in the
      United States by contributing to the understanding the diversity within this
      group. 

PMID- 26306178
TI  - Maternal effects on offspring size and number in mosquitofish, Gambusia
      holbrooki.
AB  - Given a trade-off between offspring size and number, all mothers are predicted to
      produce the same optimal-sized offspring in a given environment. In many species,
      however, larger and/or older mothers produce bigger offspring. There are several
      hypotheses to explain this but they lack strong empirical support. In organisms
      with indeterminate growth, there is the additional problem that maternal size and
      age are positively correlated, so what are their relative roles in determining
      offspring size? To investigate this, we measured the natural relationship between
      maternal and offspring size in a wild population of Gambusia holbrooki (eastern
      mosquitofish), and experimentally disentangled the effects of maternal age and
      size on offspring size in the laboratory. In combination, our data indicate that
      the relationship between maternal and offspring size is nonlinear. Small mothers
      seem to produce larger than average offspring due to integer effects associated
      with very small broods. For extremely large mothers, which were only sampled in
      our wild data, these larger than average offspring may result from greater
      maternal resources or age effects. However, maternal age had no effect on
      offspring size or number in the laboratory experiment. Our results highlight the
      importance of sampling the full size-range of mothers when investigating maternal
      effects on offspring size. They also point to the difficulty of experimentally
      manipulating maternal size, because any change in size is invariably associated
      with a change in at least one factor affecting growth (be it temperature, food
      availability, or density) that might also have an indirect effect on offspring
      size. 

PMID- 26306179
TI  - Interactive effects of elevated CO2 and precipitation change on leaf nitrogen of
      dominant Stipa L. species.
AB  - Nitrogen (N) serves as an important mineral element affecting plant productivity
      and nutritional quality. However, few studies have addressed the interactive
      effects of elevated CO2 and precipitation change on leaf N of dominant grassland
      genera such as Stipa L. This has restricted our understanding of the responses of
      grassland to climate change. We simulated the interactive effects of elevated CO2
      concentration and varied precipitation on leaf N concentration (Nmass) of four
      Stipa species (Stipa baicalensis, Stipa bungeana, Stipa grandis, and Stipa
      breviflora; the most dominant species in arid and semiarid grassland) using open
      top chambers (OTCs). The relationship between the Nmass of these four Stipa
      species and precipitation well fits a logarithmic function. The sensitivity of
      these four species to precipitation change was ranked as follows: S. bungeana >
      S. breviflora > S. baicalensis > S. grandis. The Nmass of S. bungeana was the
      most sensitive to precipitation change, while S. grandis was the least sensitive
      among these Stipa species. Elevated CO2 exacerbated the effect of precipitation
      on Nmass. Nmass decreased under elevated CO2 due to growth dilution and a direct
      negative effect on N assimilation. Elevated CO2 reduced Nmass only in a certain
      precipitation range for S. baicalensis (163-343 mm), S. bungeana (164-355 mm), S.
      grandis (148-286 mm), and S. breviflora (130-316 mm); severe drought or excessive
      rainfall would be expected to result in a reduced impact of elevated CO2.
      Elevated CO2 affected the Nmass of S. grandis only in a narrow precipitation
      range. The effect of elevated CO2 reached a maximum when the amount of
      precipitation was 253, 260, 217, and 222 mm for S. baicalensis, S. bungeana, S.
      grandis, and S. breviflora, respectively. The Nmass of S. grandis was the least
      sensitive to elevated CO2. The Nmass of S. breviflora was more sensitive to
      elevated CO2 under a drought condition compared with the other Stipa species. 

PMID- 26306180
TI  - Ecophenotypic plasticity leads to extraordinary gastropod shells found on the
      "Roof of the World".
AB  - The often extraordinary shell forms and shapes of gastropods found in
      palaeolakes, such as the highly diverse Gyraulus fauna of the famous Steinheim
      Basin, have been puzzling evolutionary biologists for centuries, and there is an
      ongoing debate whether these aberrant shell forms are indicative of true species
      (or subspecies) or ecophenotypic morphs. Interestingly, one of the Steinheim
      Gyraulus morphs - a corkscrew-like open-coiled shell - has a recent analogue in
      the Lake Bangong drainage system on the western Tibetan Plateau. Therefore, a
      combination of morphological, molecular, palaeolimnological, and ecological
      analyses was used in this study to assess whether the extraordinary shell shape
      in Gyraulus sp. from this drainage system represents a (young) ecophenotypic
      phenomenon or if it has been genetically fixed over an extended period of time.
      Our morphological, ecological, and palaeolimnological data suggest that the
      corkscrew-like specimens remain restricted to a small pond near Lake Bangong with
      an elevated pH value and that the colonization may have occurred recently. The
      phylogenetic reconstruction based on two gene fragments shows that these
      nonplanispiral specimens cluster within the previous described Tibetan Plateau
      Gyraulus clade N2. A network analysis indicates that some haplotypes are even
      shared by planispiral and nonplanispiral specimens. Given the ephemerality of the
      phenomenon, the compact network patterns inferred, the likely young phylogenetic
      age of the aberrant Gyraulus shells studied, and the ecological peculiarities of
      the study site, we suggest that the evolution of the aberrant shell forms on the
      Tibetan Plateau could likely be considered as a rapid ecophenotypic response,
      possibly induced by ecological stress. This finding may thus have implications
      for the ongoing debate about the processes that have caused the extraordinary
      shell diversity in palaeolakes such as the Steinheim Basin. 

PMID- 26306181
TI  - Using sutures to attach miniature tracking tags to small bats for multimonth
      movement and behavioral studies.
AB  - Determining the detailed movements of individual animals often requires them to
      carry tracking devices, but tracking broad-scale movement of small bats (<30 g)
      has been limited by transmitter technology and long-term attachment methods. This
      limitation inhibits our understanding of bat dispersal and migration,
      particularly in the context of emerging conservation issues such as fatalities at
      wind turbines and diseases. We tested a novel method of attaching lightweight
      global positioning system (GPS) tags and geolocating data loggers to small bats.
      We used monofilament, synthetic, absorbable sutures to secure GPS tags and data
      loggers to the skin of anesthetized big brown bats (Eptesicus fuscus) in Colorado
      and hoary bats (Lasiurus cinereus) in California. GPS tags and data loggers were
      sutured to 17 bats in this study. Three tagged bats were recaptured 7 months
      after initial deployment, with tags still attached; none of these bats showed ill
      effects from the tag. No severe injuries were apparent upon recapture of 6
      additional bats that carried tags up to 26 days after attachment; however, one of
      the bats exhibited skin chafing. Use of absorbable sutures to affix small
      tracking devices seems to be a safe, effective method for studying movements of
      bats over multiple months, although additional testing is warranted. This new
      attachment method has the potential to quickly advance our understanding of small
      bats, particularly as more sophisticated miniature tracking devices (e.g.,
      satellite tags) become available. 

PMID- 26306183
TI  - Hyperbaric oxygen therapy for post concussion symptoms: issues may affect the
      results.
AB  - Post concussion syndrome (PCS) is a set of symptoms succeeding in 25 % of mild
      traumatic brain injury (mTBI) patients. Hyperbaric oxygen therapy (HBOT) has been
      demonstrated as an effective method for treating acute and severe TBI, but its
      efficacy in PCS remains controversial. In this editorial, we reviewed the
      clinical studies of HBOT in PCS, summarized the limitations of these studies, and
      discussed the limitations: inappropriate Sham group using room air at 1.2 or 1.3
      ATA; delayed HBO administration; subjective assessment methods; time point for
      outcome assessment and small sample size. We hope that our concerns will be
      helpful for future clinical studies of HBO therapy in TBI or other neurological
      disorders. 

PMID- 26306184
TI  - Does normobaric hyperoxia increase oxidative stress in acute ischemic stroke? A
      critical review of the literature.
AB  - Stroke, one of the most debilitating cerebrovascular and nuerological diseases,
      is a serious life-threatening condition and a leading cause of long-term adult
      disability and brain damage, either directly or by secondary complications. Most
      effective treatments for stroke are time dependent such as the only FDA-approved
      therapy, reperfusion with tissue-type plasminogen activator; thus, improving
      tissue oxygenation with normobaric hyperoxia (NBO) has been considered a logical
      and potential important therapy. NBO is considered a good approach because of its
      potential clinical advantages, and many studies suggest that NBO is
      neuroprotective, reducing ischemic brain injury and infarct volume in addition to
      improving pathologic and neurobehavorial outcomes. However, increased reactive
      oxygen species (ROS) generation may occur when tissue oxygen level is too high or
      too low. Therefore, a major concern with NBO therapy in acute ischemic stroke is
      the potential increase of ROS, which could exacerbate brain injury. The purpose
      of this review is to critically review the current literature reports on the
      effect of NBO treatment on ROS and oxidative stress with respect to acute
      ischemic stroke. Considering the available data from relevant animal models, NBO
      does not increase ROS or oxidative stress if applied for a short duration;
      therefore, the potential that NBO is a viable neuroprotective strategy for acute
      ischemic stroke is compelling. The benefits of NBO may significantly outweigh the
      risks of potential increase in ROS generation for the treatment of acute ischemic
      stroke. 

PMID- 25352980
TI  - setsApp for Cytoscape: Set operations for Cytoscape Nodes and Edges.
AB  - setsApp ( http://apps.cytoscape.org/apps/setsapp) is a relatively simple
      Cytoscape 3 app for users to handle groups of nodes and/or edges. It supports
      several important biological workflows and enables various set operations.
      setsApp provides basic tools to create sets of nodes or edges, import or export
      sets, and perform standard set operations (union, difference, intersection) on
      those sets. Automatic set partitioning and layout functions are also provided.
      The sets functionality is also exposed to users and app developers in the form of
      a set of commands that can be used for scripting purposes or integrated in other
      Cytoscape apps. 

PMID- 26306187
TI  - Crystallography is more than crystal structures.
AB  - New developments in neutron and synchrotron science and technology are discussed.

PMID- 26306188
TI  - Coherent three-dimensional X-ray cryo-imaging.
AB  - The combination of cryogenic sample temperatures with three-dimensional coherent
      diffractive imaging for the case of whole frozen-hydrated cells is discussed in
      the light of theoretical predictions of the achievable resolution. 

PMID- 26236469
TI  - Advanced and Conventional Magnetic Resonance Imaging in Neuropsychiatric Lupus.
AB  - Neuropsychiatric lupus is a major diagnostic challenge, and a main cause of
      morbidity and mortality in patients with systemic lupus erythematosus (SLE).
      Magnetic resonance imaging (MRI) is, by far, the main tool for assessing the
      brain in this disease. Conventional and advanced MRI techniques are used to help
      establishing the diagnosis, to rule out alternative diagnoses, and recently, to
      monitor the evolution of the disease. This review explores the neuroimaging
      findings in SLE, including the recent advances in new MRI methods. 

PMID- 26306189
TI  - Complexity at mesoscopic lengthscale.
AB  - Modern materials are often complex in the structure at mesoscale. The method of
      pair-density function (PDF) is a powerful tool to characterize mesoscopic
      structure, bridging short- and long-range structures. 

PMID- 26306190
TI  - Demonstration of thin film pair distribution function analysis (tfPDF) for the
      study of local structure in amorphous and crystalline thin films.
AB  - By means of normal-incidence, high-flux and high-energy X-rays, total scattering
      data for pair distribution function (PDF) analysis have been obtained from thin
      films (tf), suitable for local structure analysis. By using amorphous substrates
      as support for the films, the standard Rapid Acquisition PDF setup can be applied
      and the scattering signal from the film can be isolated from the total scattering
      data through subtraction of an independently measured background signal. No
      angular corrections to the data are needed, as would be the case for grazing
      incidence measurements. The 'tfPDF' method is illustrated through studies of as
      deposited (i.e. amorphous) and crystalline FeSb3 films, where the local structure
      analysis gives insight into the stabilization of the metastable skutterudite
      FeSb3 phase. The films were prepared by depositing ultra-thin alternating layers
      of Fe and Sb, which interdiffuse and after annealing crystallize to form the
      FeSb3 structure. The tfPDF data show that the amorphous precursor phase consists
      of corner-sharing FeSb6 octahedra with motifs highly resembling the local
      structure in crystalline FeSb3. Analysis of the amorphous structure allows the
      prediction of whether the final crystalline product will form the FeSb3 phase
      with or without excess Sb present. The study thus illustrates how analysis of the
      local structure in amorphous precursor films can help to understand
      crystallization processes of metastable phases and opens for a range of new local
      structure studies of thin films. 

PMID- 26306191
TI  - Crystal structures of eight mono-methyl alkanes (C26-C32) via single-crystal and
      powder diffraction and DFT-D optimization.
AB  - The crystal structures of eight mono-methyl alkanes have been determined from
      single-crystal or high-resolution powder X-ray diffraction using synchrotron
      radiation. Mono-methyl alkanes can be found on the cuticles of insects and are
      believed to act as recognition pheromones in some social species, e.g. ants,
      wasps etc. The molecules were synthesized as pure S enantiomers and are (S)-9
      methylpentacosane, C26H54; (S)-9-methylheptacosane and (S)-11-methylheptacosane,
      C28H58; (S)-7-methylnonacosane, (S)-9-methylnonacosane, (S)-11-methylnonacosane
      and (S)-13-methylnonacosane, C30H62; and (S)-9-methylhentriacontane, C32H66. All
      crystallize in space group P21. Depending on the position of the methyl group on
      the carbon chain, two packing schemes are observed, in which the molecules pack
      together hexagonally as linear rods with terminal and side methyl groups
      clustering to form distinct motifs. Carbon-chain torsion angles deviate by less
      than 10 degrees  from the fully extended conformation, but with one packing form
      showing greater curvature than the other near the position of the methyl side
      group. The crystal structures are optimized by dispersion-corrected DFT
      calculations, because of the difficulties in refining accurate structural
      parameters from powder diffraction data from relatively poorly crystalline
      materials. 

PMID- 26306192
TI  - A systematic structural study of halogen bonding versus hydrogen bonding within
      competitive supramolecular systems.
AB  - As halogen bonds gain prevalence in supramolecular synthesis and materials
      chemistry, it has become necessary to examine more closely how such interactions
      compete with or complement hydrogen bonds whenever both are present within the
      same system. As hydrogen and halogen bonds have several fundamental features in
      common, it is often difficult to predict which will be the primary interaction in
      a supramolecular system, especially as they have comparable strength and
      geometric requirements. To address this challenge, a series of molecules
      containing both hydrogen- and halogen-bond donors were co-crystallized with
      various monotopic, ditopic symmetric and ditopic asymmetric acceptor molecules.
      The outcome of each reaction was examined using IR spectroscopy and, whenever
      possible, single-crystal X-ray diffraction. 24 crystal structures were obtained
      and subsequently analyzed, and the synthon preferences of the competing hydrogen-
      and halogen-bond donors were rationalized against a background of calculated
      molecular electrostatic potential values. It has been shown that readily
      accessible electrostatic potentials can offer useful practical guidelines for
      predicting the most likely primary synthons in these co-crystals as long as the
      potential differences are weighted appropriately. 

PMID- 26306193
TI  - Percolating hierarchical defect structures drive phase transformation in Ce1-x Gd
      x O2-x/2: a total scattering study.
AB  - A new hierarchical approach is presented for elucidating the structural disorder
      in Ce1-x Gd x O2-x/2 solid solutions on different scale lengths. The primary goal
      of this investigation is to shed light on the relations between the short-range
      and the average structure of these materials via an analysis of disorder on the
      mesocopic scale. Real-space (pair distribution function) and reciprocal-space
      (Rietveld refinement and microstructure probing) analysis of X-ray powder
      diffraction data and electron spin resonance (ESR) investigations were carried
      out following this approach. On the local scale, Gd- and Ce-rich droplets (i.e.
      small regions a few angstroms wide) form, exhibiting either a distorted fluorite
      (CeO2) or a C-type (Gd2O3) structure in the whole compositional range. These
      droplets can then form C-type nanodomains which, for Gd concentrations x Gd <=
      0.25, are embedded in the fluorite matrix. At the site percolation threshold p C
      for a cubic lattice (x Gd = p C ? 0.311), C-type nanodomains percolate inside
      each crystallite and a structural phase transformation is observed. When this
      occurs, the peak-to-peak ESR line width DeltaH pp shows a step-like behaviour,
      which can be associated with the increase in Gd-Gd dipolar interactions. A
      general crystallographic rationale is presented to explain the fluorite-to-C-type
      phase transformation. The approach shown here could be adopted more generally in
      the analysis of disorder in other highly doped materials. 

PMID- 26306194
TI  - Exploration and exploitation of homologous series of bis(acrylamido)alkanes
      containing pyridyl and phenyl groups: beta-sheet versus two-dimensional layers in
      solid-state photochemical [2 + 2] reactions.
AB  - The homologous series of phenyl and pyridyl substituted bis(acrylamido)alkanes
      have been synthesized with the aim of systematic analysis of their crystal
      structures and their solid-state [2 + 2] reactivities. The changes in the crystal
      structures with respect to a small change in the molecular structure, that is by
      varying alkyl spacers between acrylamides and/or by varying the end groups
      (phenyl, 2-pyridyl, 3-pyridyl, 4-pyridyl) on the C-terminal of the amide, were
      analyzed in terms of hydrogen-bonding interference (N-H?Npy versus N-H?O=C) and
      network geometries. In this series, a greater tendency towards the formation of N
      H?O hydrogen bonds (beta-sheets and two-dimensional networks) over N-H?N hydrogen
      bonds was observed. Among all the structures seven structures were found to have
      the required alignments of double bonds for the [2 + 2] reaction such that the
      formations of single dimer, double dimer and polymer are facilitated. However,
      only four structures were found to exhibit such a solid-state [2 + 2] reaction to
      form a single dimer and polymers. The two-dimensional hydrogen-bonding layer via
      N-H?O hydrogen bonds was found to promote solid-state [2 + 2] photo
      polymerization in a single-crystal-to-single-crystal manner. Such two-dimensional
      layers were encountered only when the spacer between acryl amide moieties is
      butyl. Only four out of the 16 derivatives were found to form hydrates, two each
      from 2-pyridyl and 4-pyridyl derivatives. The water molecules in these structures
      govern the hydrogen-bonding networks by the formation of an octameric water
      cluster and one-dimensional zigzag water chains. The trends in the melting points
      and densities were also analyzed. 

PMID- 26306195
TI  - Human insulin polymorphism upon ligand binding and pH variation: the case of 4
      ethylresorcinol.
AB  - This study focuses on the effects of the organic ligand 4-ethylresorcinol on the
      crystal structure of human insulin using powder X-ray crystallography. For this
      purpose, systematic crystallization experiments have been conducted in the
      presence of the organic ligand and zinc ions within the pH range 4.50-8.20, while
      observing crystallization behaviour around the isoelectric point of insulin. High
      throughput crystal screening was performed using a laboratory X-ray diffraction
      system. The most representative samples were selected for synchrotron X-ray
      diffraction measurements, which took place at the European Synchrotron Radiation
      Facility (ESRF) and the Swiss Light Source (SLS). Four different crystalline
      polymorphs have been identified. Among these, two new phases with monoclinic
      symmetry have been found, which are targets for the future development of
      microcrystalline insulin drugs. 

PMID- 26306196
TI  - Serial femtosecond crystallography of soluble proteins in lipidic cubic phase.
AB  - Serial femtosecond crystallography (SFX) at X-ray free-electron lasers (XFELs)
      enables high-resolution protein structure determination using micrometre-sized
      crystals at room temperature with minimal effects from radiation damage. SFX
      requires a steady supply of microcrystals intersecting the XFEL beam at random
      orientations. An LCP-SFX method has recently been introduced in which
      microcrystals of membrane proteins are grown and delivered for SFX data
      collection inside a gel-like membrane-mimetic matrix, known as lipidic cubic
      phase (LCP), using a special LCP microextrusion injector. Here, it is
      demonstrated that LCP can also be used as a suitable carrier medium for
      microcrystals of soluble proteins, enabling a dramatic reduction in the amount of
      crystallized protein required for data collection compared with crystals
      delivered by liquid injectors. High-quality LCP-SFX data sets were collected for
      two soluble proteins, lysozyme and phycocyanin, using less than 0.1 mg of each
      protein. 

PMID- 26306197
TI  - A fluorescent paramagnetic Mn metal-organic framework based on semi-rigid pyrene
      tetra-carboxylic acid: sensing of solvent polarity and explosive nitroaromatics.
AB  - An Mn metal-organic framework (Mn-MOF), Mn-L, based on a pyrene-tetraacid linker
      (H4 L), displays a respectable fluorescence quantum yield of 8.3% in spite of the
      presence of the paramagnetic metal ions, due presumably to fixation of the metal
      ions in geometries that do not allow complete energy/charge-transfer quenching.
      Remarkably, the porous Mn-L MOF with ~25% solvent-accessible volume exhibits a
      heretofore unprecedented solvent-dependent fluorescence emission maximum,
      permitting its use as a probe of solvent polarity; the emission maxima in
      different solvents correlate excellently with Reichardt's solvent polarity
      parameter (E T (N)). Further, the applicability of Mn-L to the sensing of
      nitroaromatics via fluorescence quenching is demonstrated; the detection limit
      for TNT is shown to be 125 p.p.m. The results bring out the fact that MOFs based
      on paramagnetic metal ions can indeed find application when the quenching
      mechanisms are attenuated by certain geometries of the organic linkers of the
      MOF. 

PMID- 26306198
TI  - Quantitative analysis of intermolecular interactions in orthorhombic rubrene.
AB  - Rubrene is one of the most studied organic semiconductors to date due to its high
      charge carrier mobility which makes it a potentially applicable compound in
      modern electronic devices. Previous electronic device characterizations and first
      principles theoretical calculations assigned the semiconducting properties of
      rubrene to the presence of a large overlap of the extended pi-conjugated core
      between molecules. We present here the electron density distribution in rubrene
      at 20 K and at 100 K obtained using a combination of high-resolution X-ray and
      neutron diffraction data. The topology of the electron density and energies of
      intermolecular interactions are studied quantitatively. Specifically, the
      presence of Cpi?Cpi interactions between neighbouring tetracene backbones of the
      rubrene molecules is experimentally confirmed from a topological analysis of the
      electron density, Non-Covalent Interaction (NCI) analysis and the calculated
      interaction energy of molecular dimers. A significant contribution to the lattice
      energy of the crystal is provided by H-H interactions. The electron density
      features of H-H bonding, and the interaction energy of molecular dimers connected
      by H-H interaction clearly demonstrate an importance of these weak interactions
      in the stabilization of the crystal structure. The quantitative nature of the
      intermolecular interactions is virtually unchanged between 20 K and 100 K
      suggesting that any changes in carrier transport at these low temperatures would
      have a different origin. The obtained experimental results are further supported
      by theoretical calculations. 

PMID- 26306200
TI  - Crystal chemistry of layered structures formed by linear rigid silyl-capped
      molecules.
AB  - The crystallization behavior of methylthio- or methylsulfonyl-containing spacer
      extended Z,Z-bis-ene-yne molecules capped with trimethylsilyl groups obtained by
      (tandem) thiophene ring fragmentation and of two non-spacer extended analogs were
      investigated. The rigid and linear molecules generally crystallized in layers
      whereby the flexibility of the layer interfaces formed by the silyl groups leads
      to a remarkably rich crystal chemistry. The molecules with benzene and thiophene
      spacers both crystallized with C2/c symmetry and can be considered as merotypes.
      Increasing the steric bulk of the core by introduction of ethylenedioxythiophene
      (EDOT) gave a structure incommensurately modulated in the [010] direction.
      Further increase of steric demand in the case of a dimethoxythiophene restored
      periodicity along [010] but resulted in a doubling of the c vector. Two different
      polytypes were observed, which feature geometrically different layer interfaces
      (non-OD, order-disorder, polytypes), one with a high stacking fault probability.
      Oxidation of the methylthio groups of the benzene-based molecule to
      methylsulfonyl groups led to three polymorphs (two temperature-dependent), which
      were analyzed by Hirshfeld surface d e/d i fingerprint plots. The analogously
      oxidized EDOT-based molecule crystallized as systematic twins owing to its OD
      polytypism. Shortening of the backbone by removal of the aryl core resulted in an
      enantiomorphic structure and a further shortening by removal of a methylthio-ene
      fragment again in a systematically twinned OD polytype. 

PMID- 26306199
TI  - Three-dimensional coherent X-ray diffractive imaging of whole frozen-hydrated
      cells.
AB  - A structural understanding of whole cells in three dimensions at high spatial
      resolution remains a significant challenge and, in the case of X-rays, has been
      limited by radiation damage. By alleviating this limitation, cryogenic coherent
      diffractive imaging (cryo-CDI) can in principle be used to bridge the important
      resolution gap between optical and electron microscopy in bio-imaging. Here, the
      first experimental demonstration of cryo-CDI for quantitative three-dimensional
      imaging of whole frozen-hydrated cells using 8 keV X-rays is reported. As a proof
      of principle, a tilt series of 72 diffraction patterns was collected from a
      frozen-hydrated Neospora caninum cell and the three-dimensional mass density of
      the cell was reconstructed and quantified based on its natural contrast. This
      three-dimensional reconstruction reveals the surface and internal morphology of
      the cell, including its complex polarized sub-cellular structure. It is believed
      that this work represents an experimental milestone towards routine quantitative
      three-dimensional imaging of whole cells in their natural state with spatial
      resolutions in the tens of nanometres. 

PMID- 26306201
TI  - Erratum: Room-temperature serial crystallography using a kinetically optimized
      microfluidic device for protein crystallization and on-chip X-ray diffraction.
      Corrigendum.
AB  - The name of one of the authors in the article by Heymann et al. [(2014), IUCrJ,
      1, 349-360] is corrected.[This corrects the article DOI:
      10.1107/S2052252514016960.]. 

PMID- 26306202
TI  - Association of cadmium with diabetes in middle-aged residents of abandoned metal
      mines: the first health effect surveillance for residents in abandoned metal
      mines.
AB  - OBJECTIVE: The aim of this study was to determine the association between urinary
      cadmium (U-cd) concentration and diabetes in middle-aged Korean residents of
      abandoned mines using the first Health Effect Surveillance for Residents in
      Abandoned Metal mines (HESRAM). METHODS: This study was cross-sectional study
      conducted on 719 residents between 40-70 years in 38 abandoned metal mines in
      Korea. Data was collected by HESRAM from 2008 to 2011. The correlation
      coefficient of U-cd and fasting blood glucose, odds ratio in urinary cadmium
      tertiles and diabetes prevalence was analyzed according to the sex category.
      RESULTS: The correlation coefficient U-cd concentration and fasting blood glucose
      was 0.182 in male. Logistic regression analysis in male revealed a third tertile
      odds ratio of U-cd (2 MUg/g creatinine < U-cd) while diabetes prevalence was 1.81
      (95 % CI 1.05-3.12) with adjusted age, BMI, smoking and alcohol consumption,
      region, family income. On the other hand, the odds ratio for third tertile of U
      cd (3 MUg/g creatinine < U-cd) between diabetes prevalence in female was 1.39 (95
      % CI 0.52-3.72) in addition to adjusted menopausal status. CONCLUSIONS:
      Environmental exposure to cadmium in abandoned mine residents was associated with
      diabetes in male. Closed monitoring and periodic evaluation of the health effects
      of chronic environmental exposure on abandoned mines residents will be needed.

PMID- 26306204
TI  - Lilac and honeysuckle phenology data 1956-2014.
AB  - The dataset is comprised of leafing and flowering data collected across the
      continental United States from 1956 to 2014 for purple common lilac (Syringa
      vulgaris), a cloned lilac cultivar (S. x chinensis 'Red Rothomagensis') and two
      cloned honeysuckle cultivars (Lonicera tatarica 'Arnold Red' and L. korolkowii
      'Zabeli'). Applications of this observational dataset range from detecting
      regional weather patterns to understanding the impacts of global climate change
      on the onset of spring at the national scale. While minor changes in methods have
      occurred over time, and some documentation is lacking, outlier analyses
      identified fewer than 3% of records as unusually early or late. Lilac and
      honeysuckle phenology data have proven robust in both model development and
      climatic research.

PMID- 26306203
TI  - Global database of matched Plasmodium falciparum and P. vivax incidence and
      prevalence records from 1985-2013.
AB  - Measures of clinical incidence are necessary to help estimate the burden of a
      disease. Incidence is a metric not commonly measured in malariology because the
      longitudinal surveys required are costly and labour intensive. This database is
      an effort to collate published incidence records obtained using active case
      detection for Plasmodium falciparum and Plasmodium vivax malaria. The literature
      search methods, data abstraction procedures and data processing procedures are
      described here. A total of 1,680 spatio-temporally unique incidence records were
      collected for the database: 1,187 for P. falciparum and 493 for P. vivax. These
      data were gathered to model the relationship between clinical incidence and
      prevalence of infection and can be used for a variety of modelling exercises
      including the assessment of change in disease burden in relation to age and
      control interventions. The subset of data that have been used for such modelling
      exercises are described and identified.

PMID- 26306205
TI  - The Pacific Northwest National Laboratory library of bacterial and archaeal
      proteomic biodiversity.
AB  - This Data Descriptor announces the submission to public repositories of the PNNL
      Biodiversity Library, a large collection of global proteomics data for 112
      bacterial and archaeal organisms. The data comprises 35,162 tandem mass
      spectrometry (MS/MS) datasets from ~10 years of research. All data has been
      searched, annotated and organized in a consistent manner to promote reuse by the
      community. Protein identifications were cross-referenced with KEGG functional
      annotations which allows for pathway oriented investigation. We present the data
      as a freely available community resource. A variety of data re-use options are
      described for computational modelling, proteomics assay design and
      bioengineering. Instrument data and analysis files are available at
      ProteomeXchange via the MassIVE partner repository under the identifiers
      PXD001860 and MSV000079053. 

PMID- 26306206
TI  - A spatially comprehensive, hydrometeorological data set for Mexico, the U.S., and
      Southern Canada 1950-2013.
AB  - A data set of observed daily precipitation, maximum and minimum temperature,
      gridded to a 1/16 degrees  (~6 km) resolution, is described that spans the entire
      country of Mexico, the conterminous U.S. (CONUS), and regions of Canada south of
      53 degrees  N for the period 1950-2013. The dataset improves previous products in
      spatial extent, orographic precipitation adjustment over Mexico and parts of
      Canada, and reduction of transboundary discontinuities. The impacts of adjusting
      gridded precipitation for orographic effects are quantified by scaling
      precipitation to an elevation-aware 1981-2010 precipitation climatology in Mexico
      and Canada. Differences are evaluated in terms of total precipitation as well as
      by hydrologic quantities simulated with a land surface model. Overall, orographic
      correction impacts total precipitation by up to 50% in mountainous regions
      outside CONUS. Hydrologic fluxes show sensitivities of similar magnitude, with
      discharge more sensitive than evapotranspiration and soil moisture. Because of
      the consistent gridding methodology, the current product reduces transboundary
      discontinuities as compared with a commonly used reanalysis product, making it
      suitable for estimating large-scale hydrometeorologic phenomena. 

PMID- 26306207
TI  - A readership survey of Western Pacific Surveillance and Response Journal.

PMID- 26306208
TI  - The use of social media in public health surveillance.

PMID- 26306209
TI  - A large outbreak of enterohaemorrhagic Escherichia coli O157, caused by low-salt
      pickled Napa cabbage in nursing homes, Japan, 2012.
AB  - OBJECTIVE: In August 2012, an outbreak of enterohaemorrhagic Escherichia coli
      (EHEC) O157 infection was investigated by the City of Sapporo and Hokkaido
      Prefectural Government. The initial notification reported an illness affecting 94
      residents of 10 private nursing homes distributed across multiple areas of
      Hokkaido, the northernmost island of Japan; at this time three cases were
      confirmed as EHEC O157 infection. The objectives of the investigation were to
      identify the source of infection and recommend control measures to prevent
      further illness. METHODS: A suspected case was defined as a resident of one of
      the private nursing homes in Hokkaido who had at least one of the following
      gastrointestinal symptoms: diarrhoea, bloody stool, abdominal pain or vomiting
      between 10 July and 10 September 2012. Cases were confirmed by the presence of
      Shiga toxin 1- and 2-producing EHEC O157 in stool samples of suspected cases. We
      conducted an epidemiological analysis and an environmental investigation.
      RESULTS: We identified 54 confirmed and 53 suspected cases in 12 private nursing
      homes including five fatalities. Of the 107 cases, 102 (95%) had consumed
      pickles, all of which had been manufactured at the same facility. EHEC O157
      isolates from two pickle samples, 11 cases and two staff members of the
      processing company were indistinguishable. The company that produced the pickles
      used inadequate techniques to wash and sanitize the vegetables. DISCUSSION:
      Contaminated pickles were the likely source of this outbreak. We recommended that
      the processing company improve their methods of washing and sanitizing raw
      vegetables. As a result of this outbreak, the sanitation requirements for
      processing pickles were revised.

PMID- 26306210
TI  - Chelonitoxism outbreak caused from consuming turtle, Eastern Samar, Philippines,
      August 2013.
AB  - BACKGROUND: On 21 August 2013, the Event-based Surveillance and Response system
      of the Department of Health, Philippines captured a foodborne illness event among
      residents of a coastal village in Eastern Samar, Philippines. The suspected cause
      was the consumption of a sea turtle found near the village. A team from the
      Department of Health was sent to conduct an outbreak investigation. METHODS: A
      case was defined as any person in Arteche, Eastern Samar, who developed dry mouth
      and burning sensation in the throat from 15 August to 27 August, 2013. Severity
      of the disease was classified as mild, moderate or severe. We conducted records
      review, environmental investigation, interviews of key informants and a
      retrospective cohort study. RESULTS: Sixty-eight cases were identified; four died
      (case fatality rate = 6%). All cases had a history of turtle meat consumption.
      Dose-dependent relationship was noted between amount of turtle meat consumed and
      the risk of illness. In the cohort study, consumption of turtle meat and turtle
      meat soup were associated with illness. CONCLUSION: This study identified turtle
      meat as the source of this foodborne outbreak and emphasized the dangers of
      consuming turtle meat. Other reported cases of turtle meat poisoning in the
      Philippines suggest that turtle consumption is an ongoing practice in the
      country. By publishing information about sea turtle poisoning outbreaks in the
      Philippines, we hope to raise awareness of the potential severe health effects
      from ingesting these endangered sea creatures.

PMID- 26306211
TI  - Investigating an outbreak of staphylococcal food poisoning among travellers
      across two Australian states.
AB  - INTRODUCTION: Staphylococcus aureus is a common cause of staphylococcal food
      poisoning in Australia with several outbreaks associated with foods prepared by
      commercial caterers. Laboratory testing on cases of gastrointestinal illness
      caused by enterotoxin-producing S. aureus is not routinely done as this condition
      is self-limiting. Hence outbreaks of such illness may go undetected. METHODS: A
      retrospective cohort study was conducted among a group of tourists who were
      hospitalized in Sydney shortly after flying from Queensland. The group had
      consumed food prepared by a restaurant on the Gold Coast before transit.
      Laboratory analyses on stool specimens were conducted in Sydney. An environmental
      assessment of the restaurant in the Gold Coast was conducted, and environmental
      specimens were assessed for contamination. RESULTS: Epidemiological
      investigations linked the outbreak to a restaurant in the Gold Coast where the
      suspected food was produced. Stool samples from two of the hospitalized cases
      were confirmed to have enterotoxin-producing S. aureus, and several environmental
      samples were found to be contaminated with S. aureus as well. Investigations
      suggested that absence of hand washing and other unhygienic food handling at the
      implicated restaurant was the likely cause of this outbreak. CONCLUSION: Food
      poisoning due to toxin-mediated S. aureus is frequently undetected and
      underreported. Public health units should consider toxin-producing pathogens such
      as S. aureus when investigating outbreaks where vomiting is the predominant
      symptom and occurs rapidly after consuming food.

PMID- 26306212
TI  - Lethal paralytic shellfish poisoning from consumption of green mussel broth,
      Western Samar, Philippines, August 2013.
AB  - BACKGROUND: In July 2013, the Philippines' Event-Based Surveillance & Response
      Unit received a paralytic shellfish poisoning (PSP) report from Tarangnan,
      Western Samar. A team from the Department of Health conducted an outbreak
      investigation to identify the implicated source and risk factors in coastal
      villages known for green mussel production and exportation. METHODS: A case was
      defined as a previously well individual from Tarangan, Western Samar who
      developed gastrointestinal symptoms and any motor and/or sensory symptoms after
      consumption of shellfish from 29 June to 4 July 2013 in the absence of any known
      cause. The team reviewed medical records, conducted active case finding and a
      case-control study. Relatives of cases who died were interviewed. Sera and urine
      specimens, green mussel and seawater samples were tested for saxitoxin levels
      using high performance liquid chromatography. RESULTS: Thirty-one cases and two
      deaths were identified. Consumption of > 1 cup of green mussel broth was
      associated with being a case. Seawater sample was positive for Pyrodinium
      bahamense var. compressum and green mussel samples were positive for saxitoxin.
      Inspection revealed villagers practice open defecation and improper garbage
      disposal. CONCLUSION: This PSP outbreak was caused by the consumption of the
      green mussel broth contaminated by saxitoxin. As a result of this outbreak,
      dinoflagellate and saxitoxin surveillance was established, and since the
      outbreak, there have been no harmful algal blooms event or PSP case reported
      since. A "Save Cambatutay Bay" movement, focusing on proper waste disposal
      practice and clean-up drives has been mobilized.

PMID- 26306213
TI  - Investigation of hepatitis A outbreak in district of Manjung, Perak, Malaysia,
      October 2012.
AB  - BACKGROUND: In September 2012, 10 cases suspected to be hepatitis A were notified
      to the Manjung District Health Department. An investigation was conducted to
      identify the possible mode of transmission, source of the outbreak and to
      recommend prevention and control measures. METHODS: A case was a person with
      acute illness with discrete onset of symptoms and jaundice or elevated serum
      aminotransferase levels in September 2012 in the Manjung District. We conducted a
      case-control study and environmental assessments of processing plants and food
      premises. RESULTS: There were 78 confirmed cases of hepatitis A; an attack rate
      of 3.1 per 10,000 population. Multiple logistic regression showed that being male
      (odds ratio [OR]: 18.4 [5.13-65.9]; P < 0.001) and drinking toddy at processing
      place A (Adjusted OR: 2.70 [1.17-6.25]; P < 0.05) were associated with being a
      case. Environmental investigations of this and one other processing place found
      them to be unhygienic, and the pH of the toddy was at levels that encouraged
      growth of hepatitis A virus. CONCLUSION: Toddy was possibly the primary source of
      this outbreak based on both epidemiological and environmental results. Both toddy
      preparation places and several food premises were closed as a result of this
      investigation.

PMID- 26306214
TI  - Hepatitis A outbreak in Ba subdivision, Fiji, October-December 2013.
AB  - OBJECTIVE: A cluster of suspected hepatitis A cases was notified to the Fiji
      Ministry of Health on 22 October 2013. An outbreak investigation team was
      mobilized to confirm the existence of an outbreak of hepatitis A and advise
      appropriate public health interventions. METHODS: A case definition for the
      outbreak investigation was established, and standardized data collection tools
      were used to collect information on clinical presentation and risk factors. An
      environmental assessment was also conducted. RESULTS: There were 160 clinical
      cases of hepatitis A of which 15 were laboratory-confirmed. The attack rate was
      349 per 10,000 population in the Nukuloa nursing zone; there were no reported
      deaths. Residents of the Nukuloa settlement were 6.6 times more likely to present
      with symptomatic hepatitis A infection (95% confidence interval: 3.8-12.6)
      compared with residents of another village with a different water supply.
      DISCUSSION: This is the first significant hepatitis A outbreak documented in Ba
      subdivision and possibly in Fiji. Enhanced surveillance of hepatitis A may reveal
      other clusters in the country. Improving the primary water source dramatically
      reduced the occurance of disease in the affected community and adjacent areas.

PMID- 26306215
TI  - New South Wales annual vaccine-preventable disease report, 2013.
AB  - AIM: To describe the epidemiology of selected vaccine-preventable diseases in New
      South Wales, Australia for 2013. METHODS: Data from the New South Wales
      Notifiable Conditions Information Management System were analysed by local health
      district of residence, age, Aboriginality, vaccination status and organism. Risk
      factor and vaccination status data were collected by public health units.
      RESULTS: Pertussis notification rates in infants were low, and no infant
      pertussis deaths were reported. Despite a high number of imported measles cases,
      there was limited secondary transmission. The invasive meningococcal disease
      notification rate declined, and disease due to serogroup C remained low and
      stable. CONCLUSION: Vaccine-preventable diseases were relatively well controlled
      in New South Wales in 2013, with declining or stable notification rates in most
      diseases compared with the previous year.

PMID- 26306216
TI  - Risk posed by the Ebola epidemic to the Pacific islands: findings of a recent
      World Health Organization assessment.
AB  - OBJECTIVE: To assess the public health risk posed by the ongoing Ebola virus
      disease (EVD) epidemic in West Africa to Pacific island countries and areas and
      to highlight priority risk management actions for preparedness and response.
      METHOD: The likelihood of EVD importation and the magnitude of public health
      impact in Pacific island countries and areas were assessed to determine overall
      risk. Literature about the hazard, epidemiology, exposure and contextual factors
      associated with EVD was collected and reviewed. Epidemiological information from
      the current EVD outbreak was assessed. RESULTS: As of 11 March 2015, there have
      been more than 24,200 reported cases of EVD and at least 9976 deaths in six West
      African countries. Three EVD cases have been infected outside of the West African
      region, and all have epidemiological links to the outbreak in West Africa.
      Pacific island countries' and areas' relative geographic isolation and lack of
      travel or trade links between countries with transmission means that EVD
      importation is very unlikely. However, should a case be imported, the health and
      non-health consequences would be major. The capacity of Pacific island countries
      and areas to respond adequately varies greatly between (and within) states but in
      general is limited. DISCUSSION: This risk assessment highlights the needs to
      enhance preparedness for EVD in the Pacific by strengthening the capacities
      outlined in the World Health Organization Framework for Action on Ebola. Priority
      areas include the ability to detect and respond to suspected EVD cases quickly,
      isolation and management of cases in appropriately resourced facilities and the
      prevention of further cases through infection prevention and control. These
      efforts for Ebola should enhance all-hazards public health preparedness in line
      with the International Health Regulations (2005).

PMID- 26306217
TI  - Responding to a measles outbreak in a Pacific island community in western Sydney:
      community interviews led to church-based immunization clinics.
AB  - INTRODUCTION: There are large Pacific island communities in western and south
      western Sydney, New South Wales, Australia. In 2011 and 2012, measles outbreaks
      disproportionally affected children and youth within these communities. The
      objectives of this study were to explore barriers to immunization in a Pacific
      island community from the perspectives of community members and health
      professionals and to conduct a pilot programme whereby immunization catch-up
      clinics were held in a Samoan church in western Sydney. METHODS: Interviews were
      conducted with Pacific island community members (n = 12) and health professionals
      connected with the Pacific island community (n = 7) in 2013. A partnership with a
      local Samoan church was established to provide an accessible venue for
      immunization catch-up clinics. RESULTS: Among the community members there were
      high levels of belief in the importance of immunization and a positive view
      regarding the protection offered by immunization. A key barrier reported by
      community members was being busy and therefore having limited time to get
      children immunized. The important role of the church within the community was
      emphasized in the interviews, and as a result, two immunization catch-up clinics
      were held in a Samoan church in western Sydney. The age range of attendees was 7
      33 years. A total of 31 measles, mumps and rubella doses and 19 meningococcal C
      doses were given during the two clinics. DISCUSSION: The outcomes of the
      interviews and the subsequent clinics highlighted the potential of churches as a
      venue for providing public health interventions such as catch-up immunization.

PMID- 26306218
TI  - Strengthening capacity for local evidence to inform local responses to HIV in a
      remote Solomon Islands health service.
AB  - BACKGROUND: Documenting specific knowledge and attitudes about HIV in the
      culturally diverse nation of Solomon Islands is essential to inform locally
      targeted public health responses. As part of a large capacity-strengthening
      project at Atoifi Adventist Hospital in East Kwaio, Solomon Islands, researchers,
      using a 'learn-by-doing' process, worked with participants in public health
      research methods. METHODS: Overall, 43 people attended research capacity building
      workshops in 2011; eight joined the HIV study group. A cross-sectional survey
      including semi-structured interviews on HIV was conducted by the group. In
      February 2014, a hospital administrator was interviewed about how the 2011 study
      informed local HIV responses. RESULTS: Of the 53 survey participants, 64% self
      assessed as having little or no HIV knowledge, but 90% knew HIV could be
      transmitted between men and women during sex. Less than 50% knew HIV could be
      transmitted between two men having sex, 45% thought HIV could be transmitted by
      mosquitoes and 55% agreed condoms help protect from HIV. Most participants
      reported negative attitudes towards people with HIV. Three years later the health
      administrator reported ad hoc responses to HIV because of low HIV prevalence,
      increasing noncommunicable diseases, staff turnover and resource shortages.
      DISCUSSION: This HIV study was used to strengthen research skills in local health
      professionals and community members in Solomon Islands. It showed that community
      members require accurate information about HIV transmission and that entrenched
      stigma is an issue. Although results provided local evidence for local response,
      ongoing health system challenges and little local HIV transmission meant HIV
      services remain rudimentary.

PMID- 26306219
TI  - Leveraging social networking sites for disease surveillance and public sensing:
      the case of the 2013 avian influenza A(H7N9) outbreak in China.
AB  - We conducted in-depth analysis on the use of a popular Chinese social networking
      and microblogging site, Sina Weibo, to monitor an avian influenza A(H7N9)
      outbreak in China and to assess the value of social networking sites in the
      surveillance of disease outbreaks that occur overseas. Two data sets were
      employed for our analysis: a line listing of confirmed cases obtained from
      conventional public health information channels and case information from Weibo
      posts. Our findings showed that the level of activity on Weibo corresponded with
      the number of new cases reported. In addition, the reporting of new cases on
      Weibo was significantly faster than those of conventional reporting sites and non
      local news media. A qualitative review of the functions of Weibo also revealed
      that Weibo enabled timely monitoring of other outbreak-relevant information,
      provided access to additional crowd-sourced epidemiological information and was
      leveraged by the local government as an interactive platform for risk
      communication and monitoring public sentiment on the policy response. Our
      analysis demonstrated the potential for social networking sites to be used by
      public health agencies to enhance traditional communicable disease surveillance
      systems for the global surveillance of overseas public health threats. Social
      networking sites also can be used by governments for calibration of response
      policies and measures and for risk communication. 

PMID- 26306220
TI  - First round of external quality assessment of dengue diagnostics in the WHO
      Western Pacific Region, 2013.
AB  - OBJECTIVE: Accurate laboratory testing is a critical component of dengue
      surveillance and control. The objective of this programme was to assess dengue
      diagnostic proficiency among national-level public health laboratories in the
      World Health Organization (WHO) Western Pacific Region. METHODS: Nineteen
      national-level public health laboratories performed routine dengue diagnostic
      assays on a proficiency testing panel consisting of two modules: one containing
      commercial serum samples spiked with cultured dengue viruses for the detection of
      nucleic acid and non-structural protein 1 (NS1) (Module A) and one containing
      human serum samples for the detection of anti-dengue virus antibodies (Module B).
      A review of logistics arrangements was also conducted. RESULTS: All 16
      laboratories testing Module A performed reverse transcriptase polymerase chain
      reaction (RT-PCR) for both RNA and serotype detection. Of these, 15 had correct
      results for RNA detection and all 16 correctly serotyped the viruses. All nine
      laboratories performing NS1 antigen detection obtained the correct results.
      Sixteen of the 18 laboratories using IgM assays in Module B obtained the correct
      results as did the 13 laboratories that performed IgG assays. Detection of
      ongoing/recent dengue virus infection by both molecular (RT-PCR) and serological
      methods (IgM) was available in 15/19 participating laboratories. DISCUSSION: This
      first round of external quality assessment of dengue diagnostics was successfully
      conducted in national-level public health laboratories in the WHO Western Pacific
      Region, revealing good proficiency in both molecular and serological testing.
      Further comprehensive diagnostic testing for dengue virus and other priority
      pathogens in the Region will be assessed during future rounds.

PMID- 26306221
TI  - Epidemiological update on the dengue situation in the Western Pacific Region,
      2012.
AB  - Dengue has caused a substantial public health burden in the Western Pacific
      Region. To assess this burden and regional trends, data were collated and
      summarized from indicator-based surveillance systems on dengue cases and deaths
      from countries and areas in the Western Pacific Region. In 2012, dengue
      notifications continued to increase with 356,838 dengue cases reported in the
      Region (relative to 244,855 cases reported in 2011) of which 1248 died. In the
      Asia subregion, the notification rate was highest in Cambodia, the Philippines
      and the Lao People's Democratic Republic (316.2, 198.9 and 162.4 per 100,000
      population, respectively), and in the Pacific island countries and areas, the
      notification rate was highest in Niue, the Marshall Islands and the Federated
      States of Micronesia (8556.0, 337.0 and 265.1 per 100,000 population,
      respectively). All four serotypes were circulating in the Region in 2012 with
      considerable variabilitiy in distribution. Regional surveillance provides
      important information to enhance situational awareness, conduct risk assessments
      and improve preparedness activities.

PMID- 26306222
TI  - Chelonitoxism outbreak: Sorsogon, Philippines, October 2014.

PMID- 26306223
TI  - Adverse Drug Event Ontology: Gap Analysis for Clinical Surveillance Application.
AB  - Adverse drug event identification and management are an important patient safety
      problem given the potential for event prevention. Previous efforts to provide
      structured data methods for population level identification of adverse drug
      events have been established, but important gaps in coverage remain. ADE
      identification gaps contribute to suboptimal and inefficient event
      identification. To address the ADE identification problem, a gap assessment was
      completed with the creation of a proposed comprehensive ontology using a Minimal
      Clinical Data Set framework incorporating existing identification approaches,
      clinical literature and a large set of inpatient clinical data. The new ontology
      was developed and tested using the National Inpatient Sample database with the
      validation results demonstrating expanded ADE identification capacity. In
      addition, the newly proposed ontology elements are noted to have significant
      inpatient mortality, above median inpatient costs and a longer length of stay
      when compared to existing ADE ontology elements and patients without ADE
      exposure. 

PMID- 26306224
TI  - Integrating Gene Regulatory Networks to identify cancer-specific genes.
AB  - Consensus approaches have been widely used to identify Gene Regulatory Networks
      (GRNs) that are common to multiple studies. However, in this research we develop
      an application that semi-automatically identifies key mechanisms that are
      specific to a particular set of conditions. We analyse four different types of
      cancer to identify gene pathways unique to each of them. To support the results
      reliability we calculate the prediction accuracy of each gene for the specified
      conditions and compare to predictions on other conditions. The most predictive
      are validated using the GeneCards encyclopaedia1 coupled with a statistical test
      for validating clusters. Finally, we implement an interface that allows the user
      to identify unique subnetworks of any selected combination of studies using AND &
      NOT logic operators. Results show that unique genes and sub-networks can be
      reliably identified and that they reflect key mechanisms that are fundamental to
      the cancer types under study. 

PMID- 26306225
TI  - Leveraging an Electronic Health Record-Linked Biorepository to Generate a
      Metformin Pharmacogenomics Hypothesis.
AB  - Metformin is a first-line antihyperglycemic agent commonly prescribed in type 2
      diabetes mellitus (T2DM), but whose pharmacogenomics are not clearly understood.
      Further, due to accumulating evidence highlighting the potential for metformin in
      cancer prevention and treatment efforts it is imperative to understand molecular
      mechanisms of metformin. In this electronic health record(EHR)-based study we
      explore the potential association of the flavin-containing monooxygenase(FMO)-5
      gene, a biologically plausible biotransformer of metformin, and modifying
      glycemic response to metformin treatment. Using a cohort of 258 T2DM patients who
      had new metformin exposure, existing genetic data, and longitudinal electronic
      health records, we compared genetic variation within FMO5 to change in glycemic
      response. Gene-level and SNP-level analysis identified marginally significant
      associations for FMO5 variation, representing an EHR-driven pharmacogenetics
      hypothesis for a potential novel mechanism for metformin biotransformation.
      However, functional validation of this EHR-based hypothesis is necessary to
      ascertain its clinical and biological significance. 

PMID- 26306226
TI  - Novel Application of Junction Trees to the Interpretation of Epigenetic
      Differences among Lung Cancer Subtypes.
AB  - In this era of precision medicine, understanding the epigenetic differences in
      lung cancer subtypes could lead to personalized therapies by possibly reversing
      these alterations. Traditional methods for analyzing microarray data rely on the
      use of known pathways. We propose a novel workflow, called Junction trees to
      Knowledge (J2K) framework, for creating interpretable graphical representations
      that can be derived directly from in silico analysis of microarray data. Our
      workflow has three steps, preprocessing (discretization and feature selection),
      construction of a Bayesian network and, its subsequent transformation into a
      Junction tree. We used data from the Cancer Genome Atlas to perform preliminary
      analyses of this J2K framework. We found relevant cliques of methylated sites
      that are junctions of the network along with potential methylation biomarkers in
      the lung cancer pathogenesis. 

PMID- 26306227
TI  - Automated Determination of Publications Related to Adverse Drug Reactions in
      PubMed.
AB  - Timely dissemination of up-to-date information concerning adverse drug reactions
      (ADRs) at the point of care can significantly improve medication safety and
      prevent ADRs. Automated methods for finding relevant articles in MEDLINE which
      discuss ADRs for specific medications can facilitate decision making at the point
      of care. Previous work has focused on other types of clinical queries and on
      retrieval for specific ADRs or drug-ADR pairs, but little work has been published
      on finding ADR articles for a specific medication. We have developed a method to
      generate a PubMED query based on MESH, supplementary concepts, and textual terms
      for a particular medication. Evaluation was performed on a limited sample,
      resulting in a sensitivity of 90% and precision of 93%. Results demonstrated that
      this method is highly effective. Future work will integrate this method within an
      interface aimed at facilitating access to ADR information for specified drugs at
      the point of care. 

PMID- 26306228
TI  - How Comorbidities Co-Occur in Readmitted Hip Fracture Patients: From Bipartite
      Networks to Insights for Post-Discharge Planning.
AB  - Although a majority of 30-day readmissions of hip-fracture (HFx) patients in the
      elderly are caused by non-surgical complications, little is known about which
      specific combinations of comorbidities are associated with increased risk of
      readmission. We therefore used bipartite network analysis to explore the complex
      associations between 70 comorbidities (defined by hierarchal condition categories
      as critical in this population) and (a) cases consisting of all 2,316 HFx
      patients without hospital complications in the 2010 Medicare claims database who
      were re-admitted within 30 days of discharge, and (b) controls consisting of an
      equal number of matched HFx patients who were not readmitted for at least 90 days
      since discharge. A network-wide analysis revealed nine patient/comorbidity co
      clusters, of which two had a significantly different proportion of cases compared
      to the rest of the data. A cluster-specific analysis of the most significant co
      cluster revealed that a pair of comorbidities (Renal Failure and Diabetes with no
      Complications) within the co-cluster had significantly higher risk of 30-day
      readmission, whereas another pair of comorbidities (Renal Failure and Diabetes
      with Renal or Peripheral Circulatory Manifestations), despite having a relatively
      more serious comorbidity, did not confer a higher risk. This counter-intuitive
      result suggests that HFx patients with more serious comorbidities may have better
      follow-up that reduces the risk of 30-day readmission, whereas those with
      specific relatively less-serious comorbidities may have less stringent follow-up
      resulting in unanticipated incidents that precipitate readmission. These analyses
      reveal the strengths and limitations of bipartite networks for identifying
      hypotheses for complex phenomena related to readmissions, with the goal of
      improving follow-up care for patients with specific combinations of
      comorbidities. 

PMID- 26306229
TI  - Analysis of Viral Genetics for Estimating Diffusion of Influenza A H6N1.
AB  - H6N1 influenza A is an avian virus but in 2013 infected a human in Taiwan. We
      studied the phylogeography of avian origin H6N1 viruses in the Influenza Research
      Database and the Global Initiative on Sharing Avian Influenza Data EpiFlu
      Database in order to characterize their recent evolutionary spread. Our results
      suggest that the H6N1 virus that infected a human in Taiwan is derived from a
      diversity of avian strains of H6N1 that have circulated for at least seven years
      in this region. Understanding how geography impacts the evolution of avian
      influenza could allow disease control efforts to focus on areas that pose the
      greatest risk to humans. The serious human infection with a known avian influenza
      virus underscores the zoonotic potential of diverse avian strains of influenza,
      and the need for comprehensive influenza surveillance in animals and the value of
      public sequence databases including GISAID and the IRD. 

PMID- 26306230
TI  - Studying the Confounding Effects of Socio-Ecological Conditions in Retrospective
      Clinical Research: A Use Case of Social Stress.
AB  - Socio-ecological Conditions (SECs) are important to include in clinical research
      models as they have been known to impact the health of patients. However, current
      clinical research models account for these factors only in an unsatisfyingly
      rudimentary way. In this study, we developed an SEC Index that captured the
      latent and direct effects of social stress, one of the many kinds of SEC, on
      patients' general health as measured by the Charlson Comorbidity Index. We
      demonstrated that the above SEC Index had a significant effect in a clinical
      model, a patient-level model with the specific clinical outcome of breast cancer
      prevalence. Further, we demonstrated that including the SEC Index of social
      stress into the clinical models significantly increased their performance. Our
      study demonstrated a viable approach that is interchangeable to include any SEC
      of interest, to more appropriately account for SECs in clinical research models. 

PMID- 26306231
TI  - Detecting Cancer Pathway Crosstalk with Distance Correlation.
AB  - Biological pathway regulation is complex, yet it underlies the functional
      coordination in a cell. Cancer is a disease that is characterized by unregulated
      growth, driven by underlying pathway deregulation. This pathway deregulation is
      both within pathways and between pathways. Here, we propose a method to detect
      inter-pathway coordination using distance correlation. Utilizing data generated
      from microarray experiments, we separate the genes into pathways and calculate
      the pairwise distance correlation between them. The result is intuitively viewed
      as a network of differentially dependent pathways. We find intuitive, yet
      surprising significant hub pathways, including glycophosphatidylinositol anchor
      synthesis in lung cancer. 

PMID- 26306232
TI  - Mining Relation Reversals in the Evolution of SNOMED CT Using MapReduce.
AB  - Relation reversals in ontological systems refer to such patterns as a path from
      concept A to concept B in one version becoming a path with the position of A and
      B switched in another version. We present a scalable approach, using cloud
      computing, to systematically extract all hierarchical relation reversals among 8
      SNOMED CT versions from 2009 to 2014. Taking advantage of our MapReduce
      algorithms for computing transitive closure and large-scale set operations, 48
      reversals were found through 28 pairwise comparison of the 8 versions in 18
      minutes using a 30-node local cloud, to completely cover all possible scenarios.
      Except for one, all such reversals occurred in three sub-hierarchies: Body
      Structure, Clinical Finding, and Procedure. Two (2) reversal pairs involved an
      uncoupling of the pair before the is-a coupling is reversed. Twelve (12) reversal
      pairs involved paths of length-two, and none (0) involved paths beyond length
      two. Such reversals not only represent areas of potential need for additional
      modeling work, but also are important for identifying and handling cycles for
      comparative visualization of ontological evolution. 

PMID- 26306233
TI  - ClinicalTime: Identification of Patients with Acute Kidney Injury using Temporal
      Abstractions and Temporal Pattern Matching.
AB  - INTRODUCTION: The rising cost of providing healthcare services creates an extreme
      pressure to know what works best in medicine. Traditional methods of generating
      clinical evidence are expensive and time consuming. The availability of
      electronic clinical data generated during routine patient encounters provides an
      opportunity to use that information to generate new clinical evidence. However,
      electronic clinical data is frequently marred by inadequate quality that impedes
      such secondary uses. This study provides a proof-of-concept and tests the
      classification accuracy of ClinicalTime-a temporal query system-to identify
      patient cohorts in clinical databases. METHODS: we randomly selected a sample of
      medical records from the MIMIC-II database, an anonymized database of intensive
      care patients. Records were manually classified as having an acute kidney injury
      or not according to the AKIN criteria. Those records were then blindly classified
      using ClinicalTime to represent the AKIN criteria. Classification accuracy was
      measured. RESULTS: ClinicalTime correctly classified 88% of all patients, with a
      sensitivity of 0.93 and specificity of 0.84. Its performance was superior to
      simply using ICD-9 codes, which correctly classified 66% of all patients.
      CONCLUSIONS: ClinicalTime, a temporal query system, is a valid method to add to
      the currently available ones to identify patient phenotypes in patient databases
      and, thus, improving our ability to re-use routinely collected electronic
      clinical data for secondary purposes.

PMID- 26306234
TI  - Adverse Drug Events-based Tumor Stratification for Ovarian Cancer Patients
      Receiving Platinum Therapy.
AB  - The underlying molecular mechanisms of adverse drug events (ADEs) associated with
      cancer therapy drugs may overlap with their antineoplastic mechanisms. In a
      previous study, we developed an ADE-based tumor stratification framework (known
      as ADEStrata) with a case study of breast cancer patients receiving aromatase
      inhibitors, and demonstrated that the prediction of per-patient ADE propensity
      simultaneously identifies high-risk patients experiencing poor outcomes. In this
      study, we aim to evaluate the ADEStrata framework with a different tumor type and
      chemotherapy class - ovarian cancer treated with platinum chemotherapeutic drugs.
      We identified a cohort of ovarian cancer patients receiving cisplatin (a standard
      platinum therapy) from The Cancer Genome Atlas (TCGA) (n=156). We demonstrated
      that somatic variant prioritization guided by known ADEs associated with
      cisplatin could be used to stratify patients treated with cisplatin and uncover
      tumor subtypes with different clinical outcomes. 

PMID- 26306235
TI  - Rediscovering drug side effects: the impact of analytical assumptions on the
      detection of associations in EHR data.
AB  - Large clinical datasets can be used to discover and monitor drug side effects.
      Many previous studies analyzed symptom data as discrete events. However, some
      drug side effects are inferred from continuous variables such as weight or blood
      pressure. These require additional assumptions for analysis. For example, we can
      define positive/negative thresholds and time windows within which we expect to
      see the side effect. In this paper, we discuss the impact of such assumptions on
      the ability to detect known continuous drug side effects using statistical and
      visualization techniques. Taking the case of prednisone exposure and weight gain
      reflected in real EHR data, we found that temporal windowing greatly affected the
      ability to detect the expected effect. Categorization of the exposure variable
      improved side effect detection but negatively impacted model fit. To avoid false
      positive and false negative conclusions from clinical data reuse, studies reusing
      clinical data should determine the sensitivity of their findings to alternative
      analytic assumptions. 

PMID- 26306236
TI  - Ranking Medical Subject Headings using a factor graph model.
AB  - Automatically assigning MeSH (Medical Subject Headings) to articles is an active
      research topic. Recent work demonstrated the feasibility of improving the
      existing automated Medical Text Indexer (MTI) system, developed at the National
      Library of Medicine (NLM). Encouraged by this work, we propose a novel data
      driven approach that uses semantic distances in the MeSH ontology for automated
      MeSH assignment. Specifically, we developed a graphical model to propagate belief
      through a citation network to provide robust MeSH main heading (MH)
      recommendation. Our preliminary results indicate that this approach can reach
      high Mean Average Precision (MAP) in some scenarios. 

PMID- 26306237
TI  - Visualizing Anomalies in Electronic Health Record Data: The Variability Explorer
      Tool.
AB  - As Electronic Health Record (EHR) systems are becoming more prevalent in the U.S.
      health care domain, the utility of EHR data in translational research and
      clinical decision-making gains prominence. Leveraging primay. care-based. multi
      clinic EHR data, this paper introduces a web-based visualization tool, the
      Variability Explorer Tool (VET), to assist researchers with profiling variability
      among diagnosis codes. VET applies a simple statistical method to approximate
      probability distribution functions for the prevalence of any given diagnosis
      codes to visualize between-clinic and across-year variability. In a depression
      diagnoses use case, VET outputs demonstrated substantial variability in code use.
      Even though data quality research often characterizes variability as an indicator
      for data quality, variability can also reflect real characteristics of data, such
      as practice-level, and patient-level issues. Researchers benefit from recognizing
      variability in early stages of research to improve their research design and
      ensure validity and generalizability of research findings. 

PMID- 26306238
TI  - A Probabilistic Reasoning Method for Predicting the Progression of Clinical
      Findings from Electronic Medical Records.
AB  - In this paper, we present a probabilistic reasoning method capable of generating
      predictions of the progression of clinical findings (CFs) reported in the
      narrative portion of electronic medical records. This method benefits from a
      probabilistic knowledge representation made possible by a graphical model. The
      knowledge encoded in the graphical model considers not only the CFs extracted
      from the clinical narratives, but also their chronological ordering (CO) made
      possible by a temporal inference technique described in this paper. Our
      experiments indicate that the predictions about the progression of CFs achieve
      high performance given the COs induced from patient records. 

PMID- 26306239
TI  - A knowledge-based, automated method for phenotyping in the EHR using only
      clinical pathology reports.
AB  - The secondary use of electronic health records (EHR) represents unprecedented
      opportunities for biomedical discovery. Central to this goal is, EHR-phenotyping,
      also known as cohort identification, which remains a significant challenge.
      Complex phenotypes often require multivariate and multi-scale analyses,
      ultimately leading to manually created phenotype definitions. We present Ontology
      driven Reports-based Phenotyping from Unique Signatures (ORPheUS), an automated
      approach to EHR-phenotyping. To do this we identify unique signatures of abnormal
      clinical pathology reports that correspond to pre-defined medical terms from
      biomedical ontologies. By using only the clinical pathology, or "lab", reports we
      are able to mitigate clinical biases enabling researchers to explore other
      dimensions of the EHR. We used ORPheUS to generate signatures for 858 diseases
      and validated against reference cohorts for Type 2 Diabetes Mellitus (T2DM) and
      Atrial Fibrillation (AF). Our results suggest that our approach, using solely
      clinical pathology reports, is an effective as a primary screening tool for
      automated clinical phenotyping. 

PMID- 26306240
TI  - Prevalence and Access of Secondary Source Medication Data: Evaluation of the
      Southeastern Diabetes Initiative (SEDI).
AB  - Medication non-adherence is a major public health issue, and measuring non
      adherence is a crucial step toward improving it. A paucity of retrievable data
      prevents researchers from effectively measuring, tracking and sharing outcomes on
      medication management. High quality data derived from prescribing patterns,
      including behavioral and technology-based interventions, is necessary to support
      meaningful use, improve publicly reported quality metrics, and develop strategies
      to improve medication management. Electronic health records make medication data
      more numerous and accessible, yet the reliability and utility of electronically
      available data elements that reflect adherence has not been well established. We
      sought to explore the types of medication-related data captured over time in a
      series of patient encounters (n=5500) in a population-based intervention in four
      U.S. counties in the SouthEastern Diabetes Initiative (SEDI). The purpose was to
      evaluate data generated through routine healthcare delivery that are repurposed
      (ie, "secondary use") for research/QI/population health. 

PMID- 26306241
TI  - Mining Biomedical Literature to Explore Interactions between Cancer Drugs and
      Dietary Supplements.
AB  - Interactions between cancer drugs and dietary supplements are clinically
      important and have not been extensively investigated through mining of the
      biomedical literature. We report on a previously introduced method now enhanced
      by machine learning-based filtering. Potential interactions are extracted by
      using relationships in the form of semantic predications. Semantic predications
      stored in SemMedDB, a database of structured knowledge generated from MEDLINE,
      were filtered and connected by two interaction pathways to explore potential drug
      supplement interactions (DSIs). The lasso regression filter was trained by using
      SemRep output features in an expert annotated corpus and used to rank retrieved
      predications by predicted precision. We found not only known interactions but
      also inferred several unknown potential DSIs by appropriate filtering and linking
      of semantic predications. 

PMID- 26306242
TI  - Case Study for Integration of an Oncology Clinical Site in a Semantic
      Interoperability Solution based on HL7 v3 and SNOMED-CT: Data Transformation
      Needs.
AB  - This paper describes the data transformation pipeline defined to support the
      integration of a new clinical site in a standards-based semantic interoperability
      environment. The available datasets combined structured and free-text patient
      data in Dutch, collected in the context of radiation therapy in several cancer
      types. Our approach aims at both efficiency and data quality. We combine custom
      developed scripts, standard tools and manual validation by clinical and knowledge
      experts. We identified key challenges emerging from the several sources of
      heterogeneity in our case study (systems, language, data structure, clinical
      domain) and implemented solutions that we will further generalize for the
      integration of new sites. We conclude that the required effort for data
      transformation is manageable which supports the feasibility of our semantic
      interoperability solution. The achieved semantic interoperability will be
      leveraged for the deployment and evaluation at the clinical site of applications
      enabling secondary use of care data for research. This work has been funded by
      the European Commission through the INTEGRATE (FP7-ICT-2009-6-270253) and EURECA
      (FP7-ICT-2011-288048) projects. 

PMID- 26306243
TI  - Drug Normalization for Cancer Therapeutic and Druggable Genome Target Discovery.
AB  - Heterogeneous drug data representation among different druggable genome knowledge
      resources and datasets delays effective cancer therapeutic target discovery
      within the broad scientific community. The objective of the present paper is to
      describe the challenges and lessons learned from our efforts in developing and
      evaluating a standards-based drug normalization framework targeting cancer
      druggable genome datasets. Our findings suggested that mechanisms need to be
      established to deal with spelling errors and irregularities in normalizing
      clinical drug data in The Cancer Genome Atlas (TCGA), whereas the annotations
      from NCI Thesaurus (NCIt) and PubChem are two layers of normalization that
      potentially bridge between the clinical phenotypes and the druggable genome
      knowledge for effective cancer therapeutic target discovery. 

PMID- 26306244
TI  - Modeling Flowsheet Data for Clinical Research.
AB  - Health care data included in clinical data repositories (CDRs) are increasingly
      used for quality reporting, business analytics and research; however, extended
      clinical data from interprofessional practice are seldom included. With the
      increasing emphasis on care coordination across settings, CDRs need to include
      data from all clinicians and be harmonized to understand the impact of their
      collaborative efforts on patient safety, effectiveness and efficiency. This study
      characterizes the extended clinical data derived from EHR flowsheet data that is
      available in the University of Minnesota's CDR and describes a process for
      creating an ontology that organizes that data so that it is more useful and
      accessible to researchers. The process is illustrated using a pressure ulcer
      ontology and compares ease of finding concepts in i2b2 for different data
      organization approaches. The challenges of the manual process and difficulties
      combining similar concepts are discussed. 

PMID- 26306245
TI  - Predictive Modeling for Pressure Ulcers from Intensive Care Unit Electronic
      Health Records.
AB  - Our goal in this study is to find risk factors associated with Pressure Ulcers
      (PUs) and to develop predictive models of PU incidence. We focus on Intensive
      Care Unit (ICU) patients since patients admitted to ICU have shown higher
      incidence of PUs. The most common PU incidence assessment tool is the Braden
      scale, which sums up six subscale features. In an ICU setting it's known
      drawbacks include omission of important risk factors, use of subscale features
      not significantly associated with PU incidence, and yielding too many false
      positives. To improve on this, we extract medication and diagnosis features from
      patient EHRs. Studying Braden, medication, and diagnosis features and
      combinations thereof, we evaluate six types of predictive models and find that
      diagnosis features significantly improve the models' predictive power. The best
      models combine Braden and diagnosis. Finally, we report the top diagnosis
      features which compared to Braden improve AUC by 10%. 

PMID- 26306246
TI  - Leveraging Expert Knowledge to Improve Machine-Learned Decision Support Systems.
AB  - While the use of machine learning methods in clinical decision support has great
      potential for improving patient care, acquiring standardized, complete, and
      sufficient training data presents a major challenge for methods relying
      exclusively on machine learning techniques. Domain experts possess knowledge that
      can address these challenges and guide model development. We present Advice-Based
      Learning (ABLe), a framework for incorporating expert clinical knowledge into
      machine learning models, and show results for an example task: estimating the
      probability of malignancy following a non-definitive breast core needle biopsy.
      By applying ABLe to this task, we demonstrate a statistically significant
      improvement in specificity (24.0% with p=0.004) without missing a single
      malignancy. 

PMID- 26306247
TI  - Characterizing Secondary Use of Clinical Data.
AB  - The increasing reliance on electronic health data has created new opportunities
      for the secondary use of clinical data to impact practice. We analyzed the
      secondary uses of clinical data at the University of Washington (UW) to better
      understand the types of users and uses as well as the benefits and limitations of
      these electronic data. At the UW, a diverse population is utilizing different
      elements of clinical data to conduct a wide. variety of studies. Investigators
      are using clinical data to explore research questions, determine study
      feasibility and to reduce the burden of manual chart abstraction. Discovered
      limitations include difficult-to-use data formatting, researchers' lack of
      understanding about the data structure and organization resulting in mistrust,
      and difficulty generalizing data to fit needs of many specialized users. 

PMID- 26306248
TI  - ResearchIQ: Design of a Semantically Anchored Integrative Query Tool.
AB  - An important factor influencing the pace of research activity is the ability of
      researchers to discover and leverage heterogeneous resources. Usually, researcher
      profiles, laboratory equipment, data samples, clinical trials, and other research
      resources are stored in heterogeneous datasets in large organizations. Emergent
      semantic web technologies provide novel approaches to discover, annotate and
      consequently link such resources. In this manuscript, we describe the design of
      Research Integrative Query (ResearchIQ) tool, a semantically anchored resource
      discovery platform that facilitates semantic discovery of local and publically
      available data through a single web portal designed for researchers in the
      biomedical informatics domain within The Ohio State University. 

PMID- 26306249
TI  - A Bibliometric Analysis on Cancer Population Science with Topic Modeling.
AB  - Bibliometric analysis is a research method used in library and information
      science to evaluate research performance. It applies quantitative and statistical
      analyses to describe patterns observed in a set of publications and can help
      identify previous, current, and future research trends or focus. To better guide
      our institutional strategic plan in cancer population science, we conducted
      bibliometric analysis on publications of investigators currently funded by either
      Division of Cancer Preventions (DCP) or Division of Cancer Control and Population
      Science (DCCPS) at National Cancer Institute. We applied two topic modeling
      techniques: author topic modeling (AT) and dynamic topic modeling (DTM). Our
      initial results show that AT can address reasonably the issues related to
      investigators' research interests, research topic distributions and popularities.
      In compensation, DTM can address the evolving trend of each topic by displaying
      the proportion changes of key words, which is consistent with the changes of MeSH
      headings. 

PMID- 26306250
TI  - Leveraging Interaction between Genetic Variants and Mammographic Findings for
      Personalized Breast Cancer Diagnosis.
AB  - Recent large-scale genome-wide association studies (GWAS) have identified a
      number of genetic variants associated with breast cancer which showed great
      potential for clinical translation, especially in breast cancer diagnosis via
      mammograms. However, the amount of interaction between these genetic variants and
      mammographic features that can be leveraged for personalized diagnosis remains
      unknown. Our study utilizes germline genetic variants and mammographic features
      that we collected in a breast cancer case-control study. By computing the
      conditional mutual information between the genetic variants and mammographic
      features given the breast cancer status, we identified six interaction pairs
      which elevate breast cancer risk and five interaction pairs which reduce breast
      cancer risk. 

PMID- 26306251
TI  - Infobutton usage in Patient Portal MyHealth.
AB  - Infobuttons have proven to be an important element in modern electronic health
      records (EHR), providing educational materials to both providers and patients.
      However, the usage of infobuttons in personalized health records (PHR) is only
      lightly documented in the literature. Patient-facing infobuttons pose a new
      challenge because patients have different questions and educational levels than
      professional users in EHRs. In this paper, we present usage data for patient
      facing infobuttons that have recently been integrated in Intermountain
      Healthcare's patient portal MyHealth. We summarize use patterns by usage
      classified in modules, electronic resources (eResource), and infobutton sessions.
      Based on the analysis, we propose further enhancements to the current
      implementation of infobuttons in MyHealth. 

PMID- 26306252
TI  - It's Just (Academic) Business: A Use Case in Improving Informatics Operations
      with Business Intelligence.
AB  - Academic biomedical informatics cores are beholden to funding agencies,
      institutional administration, collaborating researchers, and external agencies
      for ongoing funding and support. Services provided and translational research
      outcomes are increasingly important to monitor, report and analyze, to
      demonstrate value provided to the organization and the greater scientific
      community. Thus, informatics operations are also business operations. As such,
      adopting business intelligence practices offers an opportunity to improve the
      efficiency of evaluation efforts while fulfilling reporting requirements.
      Organizing informatics development documentation, service requests, and work
      performed with adaptable tools have greatly facilitated these and related
      business activities within our informatics center. Through the identification and
      measurement of key performance indicators, informatics objectives and results are
      now quickly and nimbly assessed using dashboards. Acceptance of the informatics
      operation as a business venture and the adoption of business intelligence
      strategies has allowed for data-driven decision making, faster corrective action,
      and greater transparency for interested stakeholders. 

PMID- 26306253
TI  - Mining Twitter Data to Improve Detection of Schizophrenia.
AB  - Individuals who suffer from schizophrenia comprise I percent of the United States
      population and are four times more likely to die of suicide than the general US
      population. Identification of at-risk individuals with schizophrenia is
      challenging when they do not seek treatment. Microblogging platforms allow users
      to share their thoughts and emotions with the world in short snippets of text. In
      this work, we leveraged the large corpus of Twitter posts and machine-learning
      methodologies to detect individuals with schizophrenia. Using features from
      tweets such as emoticon use, posting time of day, and dictionary terms, we
      trained, built, and validated several machine learning models. Our support vector
      machine model achieved the best performance with 92% precision and 71% recall on
      the held-out test set. Additionally, we built a web application that dynamically
      displays summary statistics between cohorts. This enables outreach to undiagnosed
      individuals, improved physician diagnoses, and destigmatization of schizophrenia.

PMID- 26306254
TI  - A Prototype for Executable and Portable Electronic Clinical Quality Measures
      Using the KNIME Analytics Platform.
AB  - Electronic clinical quality measures (eCQMs) based on the Quality Data Model
      (QDM) cannot currently be executed against non-standardized electronic health
      record (EHR) data. To address this gap, we prototyped an implementation of a QDM
      based eCQM using KNIME, an open-source platform comprising a wide array of
      computational workflow tools that are collectively capable of executing QDM-based
      logic, while also giving users the flexibility to customize mappings from site
      specific EHR data. To prototype this capability, we implemented eCQM CMS30
      (titled: Statin Prescribed at Discharge) using KNIME. The implementation contains
      value set modules with connections to the National Library of Medicine's Value
      Set Authority Center, QDM Data Elements that can query a local EHR database, and
      logical and temporal operators. We successfully executed the KNIME implementation
      of CMS30 using data from the Vanderbilt University and Northwestern University
      EHR systems. 

PMID- 26306255
TI  - Personalized Predictive Modeling and Risk Factor Identification using Patient
      Similarity.
AB  - Personalized predictive models are customized for an individual patient and
      trained using information from similar patients. Compared to global models
      trained on all patients, they have the potential to produce more accurate risk
      scores and capture more relevant risk factors for individual patients. This paper
      presents an approach for building personalized predictive models and generating
      personalized risk factor profiles. A locally supervised metric learning (LSML)
      similarity measure is trained for diabetes onset and used to find clinically
      similar patients. Personalized risk profiles are created by analyzing the
      parameters of the trained personalized logistic regression models. A 15,000
      patient data set, derived from electronic health records, is used to evaluate the
      approach. The predictive results show that the personalized models can outperform
      the global model. Cluster analysis of the risk profiles show groups of patients
      with similar risk factors, differences in the top risk factors for different
      groups of patients and differences between the individual and global risk
      factors. 

PMID- 26306256
TI  - A system for identifying and investigating unexpected response to treatment.
AB  - The availability of electronic health records creates fertile ground for
      developing computational models for various medical conditions. Using machine
      learning, we can detect patients with unexpected responses to treatment and
      provide statistical testing and visualization tools to help further analysis. The
      new system was developed to help researchers uncover new features associated with
      reduced response to treatment, and to aid physicians in identifying patients that
      are not responding to treatment as expected and hence deserve more attention. The
      solution computes a statistical score for the deviation of a given patient's
      response from responses observed individuals with similar characteristics and
      medication regimens. Statistical tests are then applied to identify clinical
      features that correlate with cohorts of patients showing deviant responses. The
      results provide comprehensive visualizations, both at the cohort and the
      individual patient levels. We demonstrate the utility of this system in a
      population of diabetic patients. 

PMID- 26306257
TI  - A Semantic Web-based System for Mining Genetic Mutations in Cancer Clinical
      Trials.
AB  - Textual eligibility criteria in clinical trial protocols contain important
      information about potential clinically relevant pharmacogenomic events. Manual
      curation for harvesting this evidence is intractable as it is error prone and
      time consuming. In this paper, we develop and evaluate a Semantic Web-based
      system that captures and manages mutation evidences and related contextual
      information from cancer clinical trials. The system has 2 main components: an NLP
      based annotator and a Semantic Web ontology-based annotation manager. We
      evaluated the performance of the annotator in terms of precision and recall. We
      demonstrated the usefulness of the system by conducting case studies in
      retrieving relevant clinical trials using a collection of mutations identified
      from TCGA Leukemia patients and Atlas of Genetics and Cytogenetics in Oncology
      and Haematology. In conclusion, our system using Semantic Web technologies
      provides an effective framework for extraction, annotation, standardization and
      management of genetic mutations in cancer clinical trials. 

PMID- 26306258
TI  - A Modular Architecture for Electronic Health Record-Driven Phenotyping.
AB  - Increasing interest in and experience with electronic health record (EHR)-driven
      phenotyping has yielded multiple challenges that are at present only partially
      addressed. Many solutions require the adoption of a single software platform,
      often with an additional cost of mapping existing patient and phenotypic data to
      multiple representations. We propose a set of guiding design principles and a
      modular software architecture to bridge the gap to a standardized phenotype
      representation, dissemination and execution. Ongoing development leveraging this
      proposed architecture has shown its ability to address existing limitations. 

PMID- 26306259
TI  - Operationalizing Semantic Medline for meeting the information needs at point of
      care.
AB  - Scientific literature is one of the popular resources for providing decision
      support at point of care. It is highly desirable to bring the most relevant
      literature to support the evidence-based clinical decision making process.
      Motivated by the recent advance in semantically enhanced information retrieval,
      we have developed a system, which aims to bring semantically enriched literature,
      Semantic Medline, to meet the information needs at point of care. This study
      reports our work towards operationalizing the system for real time use. We
      demonstrate that the migration of a relational database implementation to a NoSQL
      (Not only SQL) implementation significantly improves the performance and makes
      the use of Semantic Medline at point of care decision support possible. 

PMID- 26306260
TI  - Toward a Natural Language Interface for EHR Questions.
AB  - This paper presents a pilot study on the process of manually annotating natural
      language EHR questions with a formal meaning representation. This formal
      representation could then be used as a structured query as part of a natural
      language interface for electronic health records. This study analyzes the
      challenges of representing EHR questions as structured queries as well as the
      feasibility of creating a sufficiently large corpus of manually annotated
      structured queries for EHR questions. A set of 100 EHR questions, sampled from
      actual questions asked by ICU physicians[1], is used to perform the analysis. The
      ultimate goal of this research is to enable automatic methods for understanding
      EHR questions for use in a natural language EHR interface. 

PMID- 26306261
TI  - Cumulative Time Series Representation for Code Blue prediction in the Intensive
      Care Unit.
AB  - Patient monitors in hospitals generate a high number of false alarms that
      compromise patients care and burden clinicians. In our previous work, an attempt
      to alleviate this problem by finding combinations of monitor alarms and
      laboratory test that were predictive of code blue events, called SuperAlarms. Our
      current work consists of developing a novel time series representation that
      accounts for both cumulative effects and temporality was developed, and it is
      applied to code blue prediction in the intensive care unit (ICU). The health
      status of patients is represented both by a term frequency approach, TF, often
      used in natural language processing; and by our novel cumulative approach. We
      call this representation "weighted accumulated occurrence representation", or
      WAOR. These two representations are fed into a L1 regularized logistic regression
      classifier, and are used to predict code blue events. Our performance was
      assessed online in an independent set. We report the sensitivity of our algorithm
      at different time windows prior to the code blue event, as well as the work-up to
      detect ratio and the proportion of false code blue detections divided by the
      number of false monitor alarms. We obtained a better performance with our
      cumulative representation, retaining a sensitivity close to our previous work
      while improving the other metrics. 

PMID- 26306262
TI  - Examining Researcher Needs and Barriers for using Electronic Health Data for
      Translational Research.
AB  - To achieve the Learning Health Care System, we must harness electronic health
      data (EHD) by providing effective tools for researchers to access data
      efficiently. EHD is proliferating and researchers are relying on these data to
      pioneer discovery. Tools must be user-centric to ensure their utility. To this
      end, we conducted a qualitative study to assess researcher needs and barriers to
      using EHD. Researchers expressed the need to be confident about the data and have
      easy access, a clear process for exploration and access, and adequate resources,
      while barriers included difficulties in finding datasets, usability of the data,
      cumbersome processes, and lack of resources. These needs and barriers can inform
      the design process for innovating tools to increase utility of EHD. Understanding
      researcher needs is key to building effective user-centered EHD tools to support
      translational research. 

PMID- 26306263
TI  - Designing Ontology-based Patterns for the Representation of the Time-Relevant
      Eligibility Criteria of Clinical Protocols.
AB  - The amount of time and money required to screen patients for clinical trial and
      guideline eligibility presents the need for an automated screening process to
      streamline clinical trial enrollment and guideline implementation. This paper
      introduces an ontology-based approach for defining a set of patterns that can be
      used to represent various types of time-relevant eligibility criteria that may
      appear in clinical protocols. With a focus only on temporal requirements, we
      examined the criteria of 600 protocols and extracted a set of 37 representative
      time-relevant eligibility criteria. 16 patterns were designed to represent these
      criteria. Using a test set of an additional 100 protocols, it was found that
      these 16 patterns could sufficiently represent 98.5% of the time-relevant
      criteria. After the time-relevant criteria are modeled by these patterns, it will
      allow the potential to (1) use natural language processing algorithms to
      automatically extract temporal constraints from criteria; and (2) develop
      computer rules and queries to automate the processing of the criteria. 

PMID- 26306264
TI  - Granular Quality Reporting for Cervical Cytology Testing.
AB  - Quality reporting for cervical cancer prevention is focused on patients with
      normal cervical cytology, and excludes patients with cytological abnormalities
      that may be at higher risk. The major obstacles for granular reporting are the
      complexity of surveillance guidelines and free-text data. We performed automated
      chart review to compare the cytology testing rates for patients with 'atypical
      squamous cells of undetermined significance' (ASCUS) cytology, with the rates for
      patients with normal cytology. We modeled the surveillance guidelines, and
      extracted information from free-text cytology reports, to perform this study on
      28101 female patients. Our results show that patients with ASCUS cytology had
      significantly higher adherence rates (94.9%) than those for patients with normal
      cytology (90.4%). Overall our study indicates that the quality of care varies
      significantly between the high and average risk patients. Our study demonstrates
      the use of health information technology for higher granularity of reporting for
      cervical cytology testing. 

PMID- 26306265
TI  - A Hybrid Approach to Extracting Disorder Mentions from Clinical Notes.
AB  - Crucial information on a patient's physical or mental conditions is provided by
      mentions of disorders, such as disease, syndrome, injury, and abnormality.
      Identifying disorder mentions is one of the most significant steps in clinical
      text analysis. However, there are many surface forms of the same concept
      documented in clinical notes. Some are even recorded disjointedly, briefly, or
      intuitively. Such difficulties have challenged the information extraction systems
      that focus on identifying explicit mentions. In this study, we proposed a hybrid
      approach to disorder extraction, which leverages supervised machine learning,
      rule-based annotation, and an unsupervised NLP system. To identify different
      surface forms, we exploited rich features, especially the semantic, syntactic,
      and sequential features, for better capturing implicit relationships among words.
      We evaluated our method on the CLEF 2013 eHealth dataset. The experiments showed
      that our hybrid approach achieves a 0.776 F-score under strict evaluation
      standards, outperforming any participating systems in the Challenge. 

PMID- 26306266
TI  - Prescription Extraction from Clinical Notes: Towards Automating EMR Medication
      Reconciliation.
AB  - Medication in for ma lion is one of [he most important clinical data types in
      electronic medical records (EMR) This study developed an NLP application
      (PredMED) to extract full prescriptions and their relevant components from a
      large corpus of unstructured ambulatory office visit clinical notes and the
      corresponding structured medication reconciliation (MED REC) data in the EMR.
      PredMED achieved an 84.4% F-score on office visit encounter notes and 95.0% on
      MED"REC data, outperforming two available medication extraction systems. To
      assess the potential for using automatically extracted prescriptions in the
      medication reconciliation task, we manually analyzed discrepancies between
      prescriptions found in clinical encounter notes and in matching MED_REC data for
      sample patient encounters. 

PMID- 26306267
TI  - Research Data Explorer: Lessons Learned in Design and Development of Context
      based Cohort Definition and Selection.
AB  - Research Data eXplorer (RedX) was designed to support self-service research data
      queries and cohort identification from clinical research databases. The primary
      innovation of RedX was the electronic health record view of patient data, to
      provide better contextual understanding for non-technical users in building
      complex data queries. The design of RedX around this need identified multiple
      functions that would use individual patient views to better understand population
      based data, and vice-versa. During development, the more necessary and valuable
      components of RedX were refined, leading to a functional self-service query and
      cohort identification tool. However, with the improved capabilities and
      extensibility of other applications for data querying and navigation, our long
      term implementation and dissemination plans have moved towards consolidation and
      alignment of RedX functions as enhancements in these other initiatives. 

PMID- 26306268
TI  - Are All Vaccines Created Equal? Using Electronic Health Records to Discover
      Vaccines Associated With Clinician-Coded Adverse Events.
AB  - Adverse drug events (ADEs) are responsible for unnecessary patient deaths making
      them a major public health issue. Literature estimates 1% of ADEs recorded in
      Electronic Health Records (EHRs) are reported to federal databases making EHRs a
      vital source of ADE-related information. Using Columbia University Medical Center
      (CUMC)'s EHRs, we developed an algorithm to mine for vaccine-related ADEs
      occurring within 3 months of vaccination. In phase one, we measured the
      association between vaccinated patients with an ADE (cases) against those
      vaccinated without an ADE. To adjust for healthcare-process effects, phase two
      compared cases against those who returned to CUMC within 3 months without an ADE.
      We report 7 results passing multiplicity correction after demographic confounder
      adjustment. We observed an association, having some literature support, between
      swine flu vaccination and ADEs (H1N1v-like, OR=9.469, p<0.001; H1N1/H3N2,
      OR=3.207, p<0.001). Our algorithm could inform clinicians of the risks/benefits
      of vaccinations towards improving clinical care. 

PMID- 26306269
TI  - Towards the Standardized Documentation of E-Cigarette Use in the Electronic
      Health Record for Population Health Surveillance and Research.
AB  - The debate regarding potential negative health effects of electronic nicotine
      delivery systems (ENDS), which include electronic cigarettes, has received much
      recent attention. Currently, it is unknown whether ENDS pose a real health risk
      to users or those passively exposed to their vapor. With the increased use of
      these devices, the goal of this study was to examine if and how their use is
      being documented in the electronic health record (EHR) and the associated
      implications for clinical research. Analysis of five years of progress notes and
      tobacco use comments revealed that ENDS use is documented at an increasing rate
      with variable associated information, most often consisting of the status,
      purpose, and side effects of ENDS use. These results highlight that improved and
      consistent EHR discrete data entry for ENDS with associated clinical standards
      for documentation and representation of potential exposures are needed for
      enabling effective population health surveillance and research. 

PMID- 26306270
TI  - Disease Comorbidity Network Guides the Detection of Molecular Evidence for the
      Link Between Colorectal Cancer and Obesity.
AB  - Epidemiological studies suggested that obesity increases the risk of colorectal
      cancer (CRC). The genetic connection between CRC and obesity is multifactorial
      and inconclusive. In this study, we hypothesize that the study of shared comorbid
      diseases between CRC and obesity can offer unique insights into common genetic
      basis of these two diseases. We constructed a comorbidity network based on mining
      health data for millions of patients. We developed a novel approach and extracted
      the diseases that play critical roles in connecting obesity and CRC in the
      comorbidity network. Our approach was able to prioritize metabolic syndrome and
      diabetes, which are known to be associated with obesity and CRC through insulin
      resistance pathways. Interestingly, we found that osteoporosis was highly
      associated with the connection between obesity and CRC. Through gene expression
      meta-analysis, we identified novel genes shared among CRC, obesity and
      osteoporosis. Literature evidences support that these genes may contribute in
      explaining the genetic overlaps between obesity and CRC. 

PMID- 26306271
TI  - Integrating Multiple On-line Knowledge Bases for Disease-Lab Test Relation
      Extraction.
AB  - A computable knowledge base containing relations between diseases and lab tests
      would be a great resource for many biomedical informatics applications. This
      paper describes our initial step towards establishing a comprehensive knowledge
      base of disease and lab tests relations utilizing three public on-line resources.
      LabTestsOnline, MedlinePlus and Wikipedia are integrated to create a freely
      available, computable disease-lab test knowledgebase. Disease and lab test
      concepts are identified using MetaMap and relations between diseases and lab
      tests are determined based on source-specific rules. Experimental results
      demonstrate a high precision for relation extraction, with Wikipedia achieving
      the highest precision of 87%. Combining the three sources reached a recall of
      51.40%, when compared with a subset of disease-lab test relations extracted from
      a reference book. Moreover, we found additional disease-lab test relations from
      on-line resources, indicating they are complementary to existing reference books
      for building a comprehensive disease and lab test relation knowledge base. 

PMID- 26306272
TI  - Development of Bioinformatics Pipeline for Analyzing Clinical Pediatric NGS Data.
AB  - Using an Illumina exome sequencing dataset generated from pediatric Acute Myeloid
      Leukemia patients (AML; type FLT3/ITD+) a comprehensive bioinformatics pipeline
      was developed to aid in a better clinical understanding of the genetic data
      associated with the clinical phenotype. The pipeline starts with raw next
      generation sequencing reads and using both publicly available resources and
      custom scripts, analyzes the genomic data for variants associated with pediatric
      AML. By incorporating functional information such as Gene Ontology annotation and
      protein-protein interactions, the methodology prioritizes genomic variants and
      returns disease specific results and knowledge maps. Furthermore, it compares the
      somatic mutations at diagnosis with the somatic mutations at relapse and outputs
      variants and functional annotations that are specific for the relapse state. 

PMID- 26306273
TI  - Methods for Linking EHR Notes to Education Materials.
AB  - It has been shown that providing patients with access to their own electronic
      health records (EHR) can enhance their medical understanding and provide
      clinically relevant benefits. However, languages that are difficult for non
      medical professionals to comprehend are prevalent in the EHR notes, including
      medical terms, abbreviations, and domain-specific language patterns. Furthermore,
      limited average health literacy forms a barrier for patients to understand their
      health condition, impeding their ability to actively participate in managing
      their health. Therefore, we are developing a system to retrieve EHR note-tailored
      online consumer-oriented health education materials to improve patients' health
      knowledge of their own clinical conditions. Our experiments show that queries
      combining key concepts and other medical concepts present in the EHR notes
      significantly outperform (more than doubled) a baseline system of using the
      phrases from topic models. 

PMID- 26306274
TI  - Conceptualizing a Novel Quasi-Continuous Bayesian Phylogeographic Framework for
      Spatiotemporal Hypothesis Testing.
AB  - Continuous phylogeography is a growing approach to studying the spatiotemporal
      origins of RNA viruses because of its realistic spatial reconstruction advantages
      over discrete phylogeography. While the generalized linear model has been
      demonstrated as an effective tool for simultaneously assessing the drivers
      impacting viral diffusion in discrete phylogeography, there is no similar testing
      method in the continuous phylogeographic framework. In this paper, we take a step
      toward bridging that gap by conceptualizing a novel quasi-continuous approach
      which enables the addition of discrete locations beyond the known sampling
      locations of the virus. Our model, when fully developed into phylogeographic
      software, will enable spatiotemporal hypothesis testing of viral diffusion
      without being strictly limited to observed sampling locations. This model can
      still assess the impact of local epidemiological variables on virus spread and
      could provide public health agencies with more realistic estimates of key
      predictors and locations by utilizing a more continuous landscape. 

PMID- 26306275
TI  - NEO: Systematic Non-Lattice Embedding of Ontologies for Comparing the Subsumption
      Relationship in SNOMED CT and in FMA Using MapReduce.
AB  - A structural disparity of the subsumption relationship between FMA and SNOMED
      CT's Body Structure sub-hierarchy is that while the is-a relation in FMA has a
      tree structure, the corresponding relation in Body Structure is not even a
      lattice. This paper introduces a method called NEO, for non-lattice embedding of
      FMA fragments into the Body Structure sub-hierarchy to understand (1) this
      structural disparity, and (2) its potential utility in analyzing non-lattice
      fragments in SNOMED CT. NEO consists of four steps. First, transitive, upper- and
      down-closures are computed for FMA and SNOMED CT using MapReduce, a modern
      scalable distributed computing technique. Secondly, UMLS mappings between FMA and
      SNOMED CT concepts are used to identify equivalent concepts in non-lattice
      fragments from Body Structure. Then, non-lattice fragments in the Body Structure
      sub-hierarchy are extracted, and FMA concepts matching those in the non-lattice
      fragments are used as the seeds to generate the corresponding FMA fragments.
      Lastly, the corresponding FMA fragments are embedded to the non-lattice fragments
      for comparative visualization and analysis. After identifying 8,428 equivalent
      concepts between the collection of over 30,000 concepts in Body Structure and the
      collection of over 83,000 concepts in FMA using UMLS equivalent concept mappings,
      2,117 shared is-a relations and 5,715 mismatched relations were found. Among Body
      Structure's 90,465 non-lattice fragments, 65,968 (73%) contained one or more is-a
      relations that are in SNOMED CT but not in FMA, even though they have equivalent
      source and target concepts. This shows that SNOMED CT may be more liberal in
      classifying a relation as is-a, a potential explanation for the fragments not
      conforming to the lattice property. 

PMID- 26306276
TI  - Mining Electronic Health Records using Linked Data.
AB  - Meaningful Use guidelines have pushed the United States Healthcare System to
      adopt electronic health record systems (EHRs) at an unprecedented rate. Hospitals
      and medical centers are providing access to clinical data via clinical data
      warehouses such as i2b2, or Stanford's STRIDE database. In order to realize the
      potential of using these data for translational research, clinical data
      warehouses must be interoperable with standardized health terminologies,
      biomedical ontologies, and growing networks of Linked Open Data such as Bio2RDF.
      Applying the principles of Linked Data, we transformed a de-identified version of
      the STRIDE into a semantic clinical data warehouse containing visits, labs,
      diagnoses, prescriptions, and annotated clinical notes. We demonstrate the
      utility of this system though basic cohort selection, phenotypic profiling, and
      identification of disease genes. This work is significant in that it demonstrates
      the feasibility of using semantic web technologies to directly exploit existing
      biomedical ontologies and Linked Open Data. 

PMID- 26306277
TI  - Concept Modeling-based Drug Repositioning.
AB  - Our hypothesis is that drugs and diseases sharing similar biomedical and genomic
      concepts are likely to be related, and thus repositioning opportunities can be
      identified by ranking drugs based on the incidence of shared similar concepts
      with diseases and vice versa. To test this, we constructed a probabilistic topic
      model based on the Unified Medical Language System (UMLS) concepts that appear in
      the disease and drug related abstracts in MEDLINE. The resulting probabilistic
      topic associations were used to measure the similarity between disease and drugs.
      The success of the proposed model is evaluated using a set of repositioned drugs,
      and comparing a drug's ranking based on its similarity to the original and new
      indication. We then applied the model to rare disorders and compared them to all
      approved drugs to facilitate "systematically serendipitous" discovery of
      relationships between rare diseases and existing drugs, some of which could be
      potential repositioning candidates. 

PMID- 26306278
TI  - Secure Genomic Computation through Site-Wise Encryption.
AB  - Commercial clouds provide on-demand IT services for big-data analysis, which have
      become an attractive option for users who have no access to comparable
      infrastructure. However, utilizing these services for human genome analysis is
      highly risky, as human genomic data contains identifiable information of human
      individuals and their disease susceptibility. Therefore, currently, no
      computation on personal human genomic data is conducted on public clouds. To
      address this issue, here we present a site-wise encryption approach to encrypt
      whole human genome sequences, which can be subject to secure searching of genomic
      signatures on public clouds. We implemented this method within the Hadoop
      framework, and tested it on the case of searching disease markers retrieved from
      the ClinVar database against patients' genomic sequences. The secure search runs
      only one order of magnitude slower than the simple search without encryption,
      indicating our method is ready to be used for secure genomic computation on
      public clouds. 

PMID- 26306279
TI  - Embracing the Sparse, Noisy, and Interrelated Aspects of Patient Demographics for
      use in Clinical Medical Record Linkage.
AB  - Duplicate patient records in health information systems have received increased
      attention in recent time due to regulatory incentives to integrate the healthcare
      enterprise. Historically, most patient record matching systems have been limited
      to simple applications of the Fellegi-Sunter theory of record linkage with edit
      distance based string similarity measurements. String similarity approaches
      ignore the rich semantic information present by reducing it to a simple syntactic
      comparison of characters. This work describes an updated approach to building
      clinical medical record linkage systems, which embraces the unavoidable problems
      present in real-world patient matching. Using a ground truth dataset of a real
      patient population, we demonstrate that systems built in this fashion improve
      recall by 76% with little reduction in precision. This result empirically
      demonstrates the size of the gap between sophisticated systems and naive
      approaches. Additionally, it accentuates the difficulty in estimating the false
      negative error in this setting as previous research has reported much higher
      levels of recall, due, in part, to measuring from biased samples. 

PMID- 26306280
TI  - Incorporating Statistical Topic Models in the Retrieval of Healthcare Documents.
AB  - Patients often search for information on the web about treatments and diseases
      after they are discharged from the hospital. However, searching for medical
      information on the web poses challenges due to related terms and synonymy for the
      same disease and treatment. In this paper, we present a method that combines
      Statistical Topics Models, Language Models and Natural Language Processing to
      retrieve healthcare related documents. In addition, we test if the incorporation
      of terms extracted from the patient's discharge summary improves the retrieval
      performance. We show that the proposed framework outperformed the winner of the
      retrieval CLEF eHealth 2013 challenge by 68% in the MAP measure (0:5226 vs
      0:3108), and by 13% in NDCG (0:5202 vs 0:3637). Compared with standard language
      models, we obtain an improvement of 92% in MAP (0:2666) and 45% in NDCG.
      (0:3637). 

PMID- 26306281
TI  - Data-Mining Electronic Medical Records for Clinical Order Recommendations: Wisdom
      of the Crowd or Tyranny of the Mob?
AB  - Uncertainty and variability is pervasive in medical decision making with
      insufficient evidence-based medicine and inconsistent implementation where
      established knowledge exists. Clinical decision support constructs like order
      sets help distribute expertise, but are constrained by knowledge-based
      development. We previously produced a data-driven order recommender system to
      automatically generate clinical decision support content from structured
      electronic medical record data on >19K hospital patients. We now present the
      first structured validation of such automatically generated content against an
      objective external standard by assessing how well the generated recommendations
      correspond to orders referenced as appropriate in clinical practice guidelines.
      For example scenarios of chest pain, gastrointestinal hemorrhage, and pneumonia
      in hospital patients, the automated method identifies guideline reference orders
      with ROC AUCs (c-statistics) (0.89, 0.95, 0.83) that improve upon statistical
      prevalence benchmarks (0.76, 0.74, 0.73) and pre-existing human-expert authored
      order sets (0.81, 0.77, 0.73) (P<10(-30) in all cases). We demonstrate that data
      driven, automatically generated clinical decision support content can reproduce
      and optimize top-down constructs like order sets while largely avoiding
      inappropriate and irrelevant recommendations. This will be even more important
      when extrapolating to more typical clinical scenarios where well-defined external
      standards and decision support do not exist. 

PMID- 26306282
TI  - An ontology driven clinical evidence service providing diagnostic decision
      support in family practice.
AB  - Formulation of a working diagnostic hypothesis in family practice requires
      consideration of many differential diagnoses associated with any presenting
      patient complaint. There follows a process of refinement of the differentials to
      consider, through ruling in or out each candidate differential based on the
      confirmed presence or absence of diagnostic cues elicited during patient
      consultation. The patient safety implications of diagnostic error are potentially
      severe for patient and clinician. This paper describes a clinical evidence
      service supporting this diagnostic process. It allows decision support consumers
      to provide coded evidence-based recommendations to assist with diagnostic
      hypothesis formulation, integrated with an EHR in primary care. The solution
      implements ontology models of evidence accessible to consumers as a web service
      using open source components and standards. An implementation example is
      described that consumes the service to drive a diagnostic decision support tool
      developed for the TRANSFoRm project. 

PMID- 26306283
TI  - Predicting New Target Conditions for Drug Retesting Using Temporal Patterns in
      Clinical Trials: A Proof of Concept.
AB  - Drug discovery is costly and time-consuming. Efficient drug repurposing promises
      to accelerate drug discovery with reduced cost. However, most successful
      repurposing cases so far have been achieved by serendipity. There is a need for
      more efficient computational methods for predicting new indications for existing
      drugs. This paper conducts a retrospective analysis of the temporal patterns of
      drug intervention trials for every drug in a pair of different conditions in
      ClinicalTrials.gov, including 550 drugs used for 451 conditions between 2003 and
      2013. We found that drugs are often targeted towards conditions that are related
      by similar or identical eligibility criteria. We demonstrated the preliminary
      feasibility of predicting new target conditions for drug retesting among
      conditions with similar aggregated clinical trial eligibility criteria and
      confirmed this hypothesis using evidence from the literature. 

PMID- 26306284
TI  - Measuring Mortality Information in Clinical Data Warehouses.
AB  - The ability to track and report long-term outcomes, especially mortality, is
      essential for advancing clinical research. The purpose of this study was to
      present a framework for assessing the quality of mortality information in
      clinical research databases. Using the clinical data warehouse (CDW) at Columbia
      University Medical Center as a case study, we measured: 1) agreement in vital
      status between our institution's patient registration system and the U.S. Social
      Security Administration's Death Master File (DMF), 2) the proportion of patients
      marked as deceased according to the DMF records who had subsequent visits to our
      institution, and 3) the proportion of patients still living according to
      Columbia's CDW who were over 100 and 120 years of age. Of 33,295 deaths recorded
      in our institution's patient registration system, 13,167 (39.5%) did not exist in
      the DMF. Of 315,037 patients in our CDW who marked as deceased according to the
      DMF, 2.1% had a subsequent clinical encounter at our institution. The proportion
      of patients still living according to Columbia's CDW who were over 100 and 120
      years of age was 43.6% and 43.1%, respectively. These measures may be useful to
      other clinical research investigators seeking to assess the quality of mortality
      data (1-4). 

PMID- 26306285
TI  - Automating Identification of Multiple Chronic Conditions in Clinical Practice
      Guidelines.
AB  - Many clinical practice guidelines (CPGs) are intended to provide evidence-based
      guidance to clinicians on a single disease, and are frequently considered
      inadequate when caring for patients with multiple chronic conditions (MCC), or
      two or more chronic conditions. It is unclear to what degree disease-specific
      CPGs provide guidance about MCC. In this study, we develop a method for
      extracting knowledge from single-disease chronic condition CPGs to determine how
      frequently they mention commonly co-occurring chronic diseases. We focus on 15
      highly prevalent chronic conditions. We use publicly available resources,
      including a repository of guideline summaries from the National Guideline
      Clearinghouse to build a text corpus, a data dictionary of ICD-9 codes from the
      Medicare Chronic Conditions Data Warehouse (CCW) to construct an initial list of
      disease terms, and disease synonyms from the National Center for Biomedical
      Ontology to enhance the list of disease terms. First, for each disease guideline,
      we determined the frequency of comorbid condition mentions (a disease-comorbidity
      pair) by exactly matching disease synonyms in the text corpus. Then, we developed
      an annotated reference standard using a sample subset of guidelines. We used this
      reference standard to evaluate our approach. Then, we compared the co-prevalence
      of common pairs of chronic conditions from Medicare CCW data to the frequency of
      disease-comorbidity pairs in CPGs. Our results show that some disease-comorbidity
      pairs occur more frequently in CPGs than others. Sixty-one (29.0%) of 210
      possible disease-comorbidity pairs occurred zero times; for example, no guideline
      on chronic kidney disease mentioned depression, while heart failure guidelines
      mentioned ischemic heart disease the most frequently. Our method adequately
      identifies comorbid chronic conditions in CPG recommendations with precision
      0.82, recall 0.75, and F-measure 0.78. Our work identifies knowledge currently
      embedded in the free text of clinical practice guideline recommendations and
      provides an initial view of the extent to which CPGs mention common comorbid
      conditions. Knowledge extracted from CPG text in this way may be useful to inform
      gaps in guideline recommendations regarding MCC and therefore identify potential
      opportunities for guideline improvement. 

PMID- 26306286
TI  - Learning Semantic Tags from Big Data for Clinical Text Representation.
AB  - In clinical text mining, it is one of the biggest challenges to represent medical
      terminologies and n-gram terms in sparse medical reports using either supervised
      or unsupervised methods. Addressing this issue, we propose a novel method for
      word and n-gram representation at semantic level. We first represent each word by
      its distance with a set of reference features calculated by reference distance
      estimator (RDE) learned from labeled and unlabeled data, and then generate new
      features using simple techniques of discretization, random sampling and merging.
      The new features are a set of binary rules that can be interpreted as semantic
      tags derived from word and n-grams. We show that the new features significantly
      outperform classical bag-of-words and n-grams in the task of heart disease risk
      factor extraction in i2b2 2014 challenge. It is promising to see that semantics
      tags can be used to replace the original text entirely with even better
      prediction performance as well as derive new rules beyond lexical level. 

PMID- 26306287
TI  - Phenotyping Adverse Drug Reactions: Statin-Related Myotoxicity.
AB  - It is unclear the extent to which best practices for phenotyping disease states
      from electronic medical records (EMRs) translate to phenotyping adverse drug
      events. Here we use statin-induced myotoxicity as a case study to identify best
      practices in this area. We compared multiple phenotyping algorithms using
      administrative codes, laboratory measurements, and full-text keyword matching to
      identify statin-related myopathy from EMRs. Manual review of 300 deidentified
      EMRs with exposure to at least one statin, created a gold standard set of 124
      cases and 176 controls. We tested algorithms using ICD-9 billing codes,
      laboratory measurements of creatine kinase (CK) and keyword searches of clinical
      notes and allergy lists. The combined keyword algorithms produced were the most
      accurate (PPV=86%, NPV=91%). Unlike in most disease phenotyping algorithms,
      addition of ICD9 codes or laboratory data did not appreciably increase algorithm
      accuracy. We conclude that phenotype algorithms for adverse drug events should
      consider text based approaches. 

PMID- 26306288
TI  - Structuring Free-text Microbiology Culture Reports For Secondary Use.
AB  - Microbiology lab culture reports are a frequently used diagnostic tool for
      clinical providers. However, their incorporation into clinical surveillance
      applications and evidence-based medicine can be severely hindered by the free
      text nature of these reports. In this work, we (1) created a microbiology culture
      template to structure free-text microbiology reports, (2) generated an annotated
      microbiology report corpus, and (3) built a microbiology information extraction
      system. Specifically, we combined rule-based, hybrid, and statistical techniques
      to extract microbiology entities and fill templates for structuring data. System
      performances were favorable, with entity f1-score 0.889 and relation f1-score
      0.795. We plan to incorporate these extractions as features for our ongoing
      ventilator-associated pneumonia surveillance project, though this tool can be
      used as an upstream process in other applications. Our newly created corpus
      includes 1442 unique gram stain and culture microbiology reports generated from a
      cohort of 715 patients at the University of Washington Medical Facilities. 

PMID- 26306289
TI  - Cost-effectiveness analysis of alternative cooling strategies following cardiac
      arrest.
AB  - OBJECTIVES: Using survival and neurologic outcome as endpoints , this study
      explored the incremental cost effectiveness of three mutually exclusive cooling
      strategies employed after resuscitated out-of-hospital cardiac arrests. DESIGN:
      Economic analysis based on retrospective data collection and Markov modeling.
      SETTING: Modeling based on patients housed in a tertiary ICU setting. PATIENTS:
      Patients >18 years following resuscitation from out-of-hospital cardiac arrest.
      INTERVENTIONS: Therapeutic cooling vs. conventional care. MEASUREMENTS AND MAIN
      RESULTS: Using societal-based analytic decision modeling with a lifetime study
      horizon, incremental cost effectiveness ratios (ICERs) for blanket, peritoneal
      lavage, and V-V ECMO cooling strategies were compared with conventional care.
      Comprehensive cost data were obtained from available literature, national and
      local databases; health utility data were abstracted from previous publications
      and converted to quality-adjusted life years (QALYs)/person and stratified by
      neurologic outcome state. Future costs were discounted using a standard 3%
      discount rate. Cooling blankets produced better overall health outcomes at a
      lower cost than conventional care and V-V ECMO. Peritoneal lavage added an
      additional 0.67 QALYs at an ICER of $58,329/QALY. Monte-Carlo simulations
      incorporating uncertainty in all parameters showed that peritoneal lavage was 70%
      likely to be the preferred, cost-effective therapy if one were willing to pay
      (WTP) $100,000/QALY. CONCLUSIONS: This analysis suggests that blankets are the
      most cost effective cooling strategy for post-ROSC therapeutic hypothermia, with
      peritoneal lavage as an acceptable alternative at higher WTP thresholds. Though
      uncertainty about the optimal therapy could be reduced with additional research,
      these results can inform policy-makers and healthcare providers about cost
      effectiveness of alternative cooling modalities designed to improve neurologic
      outcome for this expanding patient population. This may be particularly relevant
      as societal-based cost effectiveness analyses become more widely incorporated
      into studies evaluating treatment for frequently encountered diseases.

PMID- 26306290
TI  - A phase II dose-escalation trial of perioperative desmopressin (1-desamino-8-d
      arginine vasopressin) in breast cancer patients.
AB  - Desmopressin (dDAVP) is a well-known peptide analog of the antidiuretic hormone
      vasopressin, used to prevent excessive bleeding during surgical procedures. dDAVP
      increases hemostatic mediators, such as the von Willebrand factor (vWF), recently
      considered a key element in resistance to metastasis. Studies in mouse models and
      veterinary trials in dogs with locally-advanced mammary tumors demonstrated that
      high doses of perioperative dDAVP inhibited lymph node and early blood-borne
      metastasis and significantly prolonged survival. We conducted a phase II dose
      escalation trial in patients with breast cancer, administering a lyophilized
      formulation of dDAVP by intravenous infusion in saline, 30-60 min before and 24 h
      after surgical resection. Primary endpoints were safety and tolerability, as well
      as selection of the best dose for cancer surgery. Secondary endpoints included
      surgical bleeding, plasma levels of vWF, and circulating tumor cells (CTCs) as
      measured by quantitative PCR of cytokeratin-19 transcripts. Only 2 of a total of
      20 patients experienced reversible adverse events, including hyponatremia (grade
      4) and hypersensitivity reaction (grade 2). Reactions were adequately managed by
      slowing the infusion rate. A reduced intraoperative bleeding was noted with
      increasing doses of dDAVP. Treatment was associated with higher vWF plasma levels
      and a postoperative drop in CTC counts. At the highest dose level evaluated (2
      MUg/kg) dDAVP appeared safe when administered in two slow infusions of 1 MUg/kg,
      before and after surgery. Clinical trials to establish the effectiveness of
      adjunctive perioperative dDAVP therapy are warranted. This trial is registered on
      www.clinicaltrials.gov (NCT01606072). 

PMID- 26306291
TI  - Abdominal wall recurrence of a gastrointestinal stromal tumor: case report.
AB  - INTRODUCTION: The gastrointestinal stromal tumors (GIST) are mesenchymal tumors,
      most commonly affecting the stomach and small bowel. Only few cases of port-site
      recurrence after laparoscopic treatment have been reported. We herein report the
      case of a parietal recurrence on the extraction incision site, 7 years after
      laparoscopic surgery for small bowel GIST. CASE REPORT: A 47 years-old female
      patient was hospitalized in November 2007 for isolated pelvic pain. CT scan
      showed an intestinal tumor with a benign aspect measuring 50 mm. A laparoscopy
      assisted resection was performed. Surgical exploration found a 7 cm small bowel
      tumor. It was extracted through a supra-pubic transversal incision without a
      wound protector and then resected. Histologic analysis revealed an intestinal
      GIST with high aggressive potential (five mitosis per field), with CD117 positive
      at the immunohistochemical examination. The patient had no adjuvant chemotherapy.
      Seven years later, the patient was readmitted for an abdominal mass at the site
      of the supra-pubic scar. Abdomino-pelvic CT scan showed a 10 * 7.5 cm solid mass
      of the abdominal wall. Percutaneous biopsies were done and the pathological
      analysis revealed a mesenchymal-cell tumor, positive to CD117 and DOG1 at the
      immunohistochemical examination. Final diagnosis was abdominal wall recurrence of
      GIST secondary to tumor-contamination during the first surgery. CONCLUSION:
      Abdominal wall recurrence of GIST after laparoscopic surgery is rarely reported.
      This complication should be avoided with preventive measures such as the use of
      extraction bags or wound protectors.

PMID- 26306292
TI  - Onion thrips (Thrips tabaci (Thysanoptera: Thripidae)) in cabbage on Prince
      Edward Island: observations on planting date and variety choice.
AB  - Onion thrips (Thrips tabaci Lindeman (Thysanoptera: Thripidae)) can be a pest in
      organic onion production on Prince Edward Island. This study was to examine the
      effect of planting time and variety on infestation levels and damage by onion
      thrips on cabbage (Brassicae oleracea capitala (L.)). A field site was planted
      with 2 main and 8 lesser varieties of cabbage over 4 planting dates. Some
      varieties were short season and harvested on July 31 with longer season varieties
      harvested on September 2. Blue sticky traps were used to capture thrips migrating
      into the field site from July 22-September 2. Traps were counted weekly and
      cabbage heads within the field site were visually surveyed for thrips. At
      harvest, heads were weighed and measured, thrips damage was assessed then the
      head was dissected and thrips counted on the first four layers of the head.
      Thrips exhibited a preference for Lennox over Bronco throughout the season
      although thrips populations were not high enough to effect economic damage in
      2014. Planting date influenced cabbage head weight and size with later plantings
      yielding the largest heads. Use of planting date and variety to avoid thrips
      populations is discussed. 

PMID- 26306293
TI  - Adaptively partitioned block-based contrast enhancement and its application to
      low light-level video surveillance.
AB  - This paper presents a dark region detection and enhancement method with low
      computational complexity for low-cost imaging devices. Conventional contrast
      enhancement methods generally have an oversaturation problem while brightness of
      the dark region increases. To solve this problem, the proposed method first
      divides an input image into dark object and bright background regions using
      adaptively partitioned blocks. Next, the contrast stretching is performed only in
      the dark region. The major advantage of the proposed method is the minimized
      block artifacts using optimally partitioned blocks using fuzzy logic and a
      refining step to accurately detect boundaries between two regions. Experimental
      results show that the proposed method can efficiently enhance the contrast of
      backlit images without the oversaturation problem. Because of low computational
      complexity, the proposed method can be applied to enhance very low light-level
      video sequences for video surveillance systems. 

PMID- 26306294
TI  - Health literacy and meeting breast and cervical cancer screening guidelines among
      Asians and whites in California.
AB  - OBJECTIVES: Empirical evidence regarding cancer screening and health literacy is
      mixed. Cancer is the leading cause of death in Asian Americans, yet screening
      rates are notably low. Using a population-based sample, we determined if health
      literacy: (1) was associated with breast and cervical cancer screening, and (2)
      helped to explain Asian cancer screening disparities. METHODS: We analyzed the
      2007 California Health Interview Survey for Asian (Japanese, Chinese, Filipino,
      Korean, Vietnamese, other Asian) and white women within age groups relevant to US
      Preventive Services Task Force (USPSTF) screening guidelines: cervical: ages 21
      65 (n = 15,210) and breast: ages 50-74 (n = 11,163). Multilevel logistic
      regression models predicted meeting USPSTF screening guidelines both with and
      without self-reported health literacy controlling for individual-level and
      contextual-level factors. RESULTS: Low health literacy significantly (p < 0.05)
      predicted lower cancer screening in final models for both cancer types. In
      unadjusted models, Asians were significantly less likely than whites to receive
      both screening types and significantly more likely to report low health literacy.
      However, in multivariable models, the addition of the low health literacy
      variable did not diminish Asian vs. white cancer screening disparities.
      CONCLUSIONS: Self-reported health literacy predicted cervical and breast cancer
      screening, but was not able to explain Asian cancer screening disparities. We
      provide new evidence to support a relationship between health literacy and cancer
      screening. Health literacy is likely a useful focus for interventions to improve
      cancer screening and ultimately reduce the burden of cancer. To specifically
      reduce Asian cancer disparities, additional areas of focus should be considered.

PMID- 26306295
TI  - Comparative nutrient composition of selected wild edible mushrooms from two agro
      ecological zones, Uganda.
AB  - In Uganda, wild mushrooms are mainly collected during the rainy season and valued
      as a traditionally nutritious food by the rural poor. However, their nutritional
      attributes have not been adequately studied and documented. Comparative nutrient
      composition of five wild edible mushroom species was determined, namely: P.
      tenucuilus, T. tyleranus, T. clypeatus, V. speciosa and T. microcarpus of sub
      humid and humid agro-ecological zones. Standard analytical techniques following
      the AOAC were used for proximate and mineral contents determinations. Vitamins
      determination followed the established standard protocols of the laboratories
      where the analyses were conducted. Combined use of nutrient concentration and
      scores were used to compare the level of the contents in the mushroom species.
      Significant differences (p < 0.05) in nutrient values were demonstrated between
      and among the mushroom species obtained from the two agro-ecological zones. On
      dry weight basis, all proximate compositions were high in mushroom species
      obtained from the humid zone with exception of the total carbohydrates and energy
      values. Irrespective of the source of the mushrooms, significant amounts were
      demonstrated in protein, dry matter, ash and total carbohydrates ranging between
      11.56-27.42%, 82.34-99.76%, 10.79-16.87%, and 37.12-61.05%, respectively. In
      comparison with recommended dietary daily intakes, the K, P, Se, Mn, Cu and Fe
      contents were relatively high with low Ca, Mg, Zn and Na. Thiamin, folic acid,
      vitamin C, and niacin levels were high but below the recommended FAO references.
      Considering mushrooms from different agro-ecological zones, significant
      differences (p < 0.05) were observed in all mushroom species in P except in T.
      clypeatus, T. tyleranus, T. microcarpus and T. clypeatus in potassium, T.
      clypeatus and T. microcarpus in Mg. Mushrooms from humid agro-ecological zones
      had relatively high overall mineral and vitamin supply potential. In conclusion,
      consumption of these mushrooms should be encouraged in supplementation of the
      staple food of the poor people. Hence, solving malnutrition problems in children,
      pregnant mothers, and the immune compromised patients such as the HIV/AIDs. 

PMID- 26306296
TI  - Application of variance components estimation to calibrate geoid error models.
AB  - The method of using Global Positioning System-leveling data to obtain orthometric
      heights has been well studied. A simple formulation for the weighted least
      squares problem has been presented in an earlier work. This formulation allows
      one directly employing the errors-in-variables models which completely descript
      the covariance matrices of the observables. However, an important question that
      what accuracy level can be achieved has not yet to be satisfactorily solved by
      this traditional formulation. One of the main reasons for this is the
      incorrectness of the stochastic models in the adjustment, which in turn allows
      improving the stochastic models of measurement noises. Therefore the issue of
      determining the stochastic modeling of observables in the combined adjustment
      with heterogeneous height types will be a main focus point in this paper.
      Firstly, the well-known method of variance component estimation is employed to
      calibrate the errors of heterogeneous height data in a combined least square
      adjustment of ellipsoidal, orthometric and gravimetric geoid. Specifically, the
      iterative algorithms of minimum norm quadratic unbiased estimation are used to
      estimate the variance components for each of heterogeneous observations.
      Secondly, two different statistical models are presented to illustrate the
      theory. The first method directly uses the errors-in-variables as a priori
      covariance matrices and the second method analyzes the biases of variance
      components and then proposes bias-corrected variance component estimators.
      Several numerical test results show the capability and effectiveness of the
      variance components estimation procedure in combined adjustment for calibrating
      geoid error model. 

PMID- 26306298
TI  - Multi-district coronary tree involvement in a 17-year-old girl with Williams
      Beuren syndrome.
AB  - We describe a case of 17-year-old Chinese girl referred to our Pediatric
      Cardiology Unit for asthenia, reduced exercise tolerance, and dyspnea. Past
      medical history was relevant for multiple chest pain episodes in childhood and
      several syncopal episodes, for which the patient had been never evaluated.
      Clinical examination, electrocardiogram, and echocardiography were compatible
      with Williams-Beuren syndrome; such condition was later confirmed by genetic
      analysis. Cardiac magnetic resonance imaging showed transmural fibrosis of the
      apex with impaired left ventricular ejection fraction (29 %), severe stenosis of
      aortic sinotubular junction with left and right coronary ostia involvement; more
      importantly, the whole coronary artery tree beyond ostia was affected by multiple
      stenosis and aneurysmatic tracts. Ascending aorta proved hypoplastic, with post
      stenotic dilation and multiple aneurysms. At the end of the diagnostic process,
      surgical risk was considered too high to proceed with the correction. The
      presented case is of educational value since it provides good iconographical
      illustration of diffuse, multiple-site coronary artery tree involvement, a rather
      rare co-morbidity in Williams-Beuren syndrome. 

PMID- 26306297
TI  - Blockade of the acute activation of mTOR complex 1 decreases hypertrophy
      development in rats with severe aortic valve regurgitation.
AB  - BACKGROUND: Hypertrophy (H) is an adaptive response of the heart to a hemodynamic
      overload. Severe left ventricular (LV) volume overload (VO) from valve
      regurgitations (aortic (AR) or mitral regurgitation) leads to eccentric LVH.
      Increased protein turnover is a major event during development of LVH and the
      mechanistic target of rapamycin (mTOR) is a key molecule for its control. The
      role of mTOR inhibition in the development of LVH using rapamycin for relatively
      short periods of time (days to a few weeks) has been studied in the past in
      pressure overload models but not in VO models. We investigated if mTOR pathway
      was activated during LVH development in a model of severe VO (AR) in rats and if
      a rapamycin treatment can slow heart remodeling in this situation. METHODS AND
      RESULTS: Male rats with severe AR were studied acutely at 2 days, at 8 weeks
      (compensated phase) and 6 months (late phase) after VO induction. mTOR complex
      (mTORC) 1 (ribosomal S6 protein phosphorylation) was activated early after AR
      induction but not later in the disease whereas mTORC2 activity levels (Akt
      phosphorylation at Ser473) remained stable. We observed that a moderate dose of
      rapamycin (2 mg/kg/day; orally) for 8 weeks prevented severe LVH caused by AR (
      46 %: p < 0.001). Rapamycin treatment specifically inhibited LV mTORC1 without
      altering mTORC2 activity at 8 weeks. Rapamycin also prevented cardiac myocyte
      hypertrophy caused by AR. CONCLUSION: Rapamycin slows hypertrophy in LV VO by
      inhibiting early activation of mTORC1 without modulating mTORC2.

PMID- 26306299
TI  - Extracellular microRNAs as Biomarkers in Human Disease.
AB  - Dysregulation of microRNA (miRNA) levels is observed in diverse disease states.
      Early studies showed that by analyzing the expression profile of miRNAs in the
      tissue sample of a diseased person, it was possible to classify the disease into
      a specific subtype. To be used for diagnostic purposes more practically, however,
      a less invasive method than tissue biopsy is required. Surprisingly, it was
      discovered that a notable amount of extracellular miRNAs circulate throughout the
      body fluids with high stability. Moreover, the expression profile of miRNAs was
      shown to differ considerably between healthy and diseased people. In addition,
      evidence has been accumulating of extracellular miRNAs acting as signaling
      molecules between distantly located cells. If the expression profile faithfully
      reflects the disease states, the profiling of extracellular miRNAs will become a
      useful means of early warning or diagnosis of diverse diseases, replacing more
      invasive biopsy methods. 

PMID- 26306300
TI  - Exploring Genetic Susceptibility to Fibromyalgia.
AB  - Fibromyalgia (FM) affects 1% to 5% of the population, and approximately 90% of
      the affected individuals are women. FM patients experience impaired quality of
      life and the disorder places a considerable economic burden on the medical care
      system. With the recognition of FM as a major health problem, many recent studies
      have evaluated the pathophysiology of FM. Although the etiology of FM remains
      unknown, it is thought to involve some combination of genetic susceptibility and
      environmental exposure that triggers further alterations in gene expression.
      Because FM shows marked familial aggregation, most previous research has focused
      on genetic predisposition to FM and has revealed associations between genetic
      factors and the development of FM, including specific gene polymorphisms involved
      in the serotonergic, dopaminergic, and catecholaminergic pathways. The aim of
      this review was to discuss the current evidence regarding genetic factors that
      may play a role in the development and symptom severity of FM. 

PMID- 26306302
TI  - Clinical Significance of MET Gene Copy Number in Patients with Curatively
      Resected Gastric Cancer.
AB  - The present study analyzed the prognostic impact of MET gene copy number in
      patients with curatively resected gastric cancer who received a combination
      regimen of cisplatin and S-1. The MET gene copy number was analyzed by use of
      quantitative real-time polymerase chain reaction. From January 2006 to July 2010,
      70 tumor samples from 74 patients enrolled in a pilot study were analyzed.
      According to a cutoff MET gene copy number of >=2 copies, a high MET gene copy
      number was observed in 38 patients (54.3%). The characteristics of the 2 groups
      divided according to MET gene copy number were similar. With a median follow-up
      duration of 26.4 months (range, 2.6-73.2 months), the estimated 3-year relapse
      free survival and overall survival rates were 54.3% and 77.4%, respectively. No
      significant association was observed between the MET gene copy number and
      survival in a multivariate analysis. The MET gene copy number investigated in
      this study was not found to be associated with prognosis in patients with
      curatively resected gastric cancer. 

PMID- 26306303
TI  - Prevalence of Smoking and Its Impact on Treatment Outcomes in Newly Diagnosed
      Pulmonary Tuberculosis Patients: A Hospital-Based Prospective Study.
AB  - There is growing evidence that tobacco smoking is an important risk factor for
      tuberculosis (TB). India, with a population of 1.26 billion, has the highest
      number of both TB patients and smokers. The convergence of these two important
      health hazards is likely severely affecting India's TB control programs. This
      study was carried out to determine the prevalence of smoking in newly diagnosed
      pulmonary TB patients and the impact of smoking on disease outcomes in a tertiary
      care hospital. All patients newly diagnosed with pulmonary TB as per the Revised
      National Tuberculosis Program of India (RNTCP) 2013 criteria were enrolled in the
      study. On the basis of their self-reported smoking status, the participants were
      classified as never smokers, current smokers, and ex-smokers. Patients were
      started on anti-TB treatment and were followed for 2 years. Among the 2350
      subjects (1,758 males and 592 females), 1,593 patients (67.78%) were never
      smokers. Current and ex-smokers numbered 757 (32.21%), of which 751 (31.95%) were
      males and 6 (0.26%) were females. Smoking was associated with more extensive lung
      disease, lung cavitation, and positive sputum smear and culture results at
      baseline. In both current smokers and ex-smokers, sputum smears and cultures were
      significantly more likely to remain positive after 2 months of treatment. Ex
      smokers and current smokers had significantly high rates of defaults, treatment
      failures, and relapses. The prevalence of smoking is very high in TB patients.
      Tobacco smoking is associated with a considerably increased risk of advanced and
      more severe disease in the form of lung cavitations, positive sputum smear and
      culture results, and slower smear and culture conversion after initiation of
      treatment. Smoking has a great negative effect on treatment completion, cure
      rates, and relapse rates in patients with pulmonary TB. 

PMID- 26306301
TI  - Optimizing the Use of Aripiprazole Augmentation in the Treatment of Major
      Depressive Disorder: From Clinical Trials to Clinical Practice.
AB  - Major depressive disorder (MDD) is a recurrent, chronic, and devastating disorder
      leading to serious impairment in functional capacity as well as increasing public
      health care costs. In the previous decade, switching therapy and dose adjustment
      of ongoing antidepressants was the most frequently chosen subsequent treatment
      option for MDD. However, such recommendations were not based on firmly proven
      efficacy data from well-designed, placebo-controlled, randomized clinical trials
      (RCTs) but on practical grounds and clinical reasoning. Aripiprazole augmentation
      has been dramatically increasing in clinical practice owing to its unique action
      mechanisms as well as proven efficacy and safety from adequately powered and well
      controlled RCTs. Despite the increased use of aripiprazole in depression, limited
      clinical information and knowledge interfere with proper and efficient use of
      aripiprazole augmentation for MDD. The objective of the present review was to
      enhance clinicians' current understanding of aripiprazole augmentation and how to
      optimize the use of this therapy in the treatment of MDD. 

PMID- 26306304
TI  - Factors Affecting the Accuracy of Intraocular Lens Power Calculation with
      Lenstar.
AB  - This retrospective study was performed to compare refractive outcomes measured by
      conventional methods and by use of the Lenstar biometer and to investigate the
      factors affecting intraocular lens (IOL) power calculation with Lenstar with and
      without IOL-constant optimization. The study included 100 eyes of 86 patients who
      underwent cataract surgery. Corneal curvature was measured with a manual
      keratometer (MK), automated keratometer (AK), and the Lenstar biometer, and axial
      length (AL) was measured by A-scan and Lenstar. Mean numerical error (MNE) and
      mean absolute error (MAE) were compared between AK and MK with A-scan, and
      Lenstar with and without optimization. Factors affecting the accuracy of the IOL
      power calculation by use of Lenstar with and without optimization were analyzed.
      No significant differences were observed in the MNE or MAE among the devices. The
      proportion of MAE within 0.5 D was higher for Lenstar with optimization (62.7%)
      than without optimization (46.2%). The proportion of MAE within 0.5 D was 62% and
      58% for MK and AK with A-scan, respectively. Without optimization, the MAE was
      smaller in eyes with ALs between 23 mm and 25 mm (p=0.03), whereas it was smaller
      at higher corneal powers when the IOL constant was optimized (>44 D, p=0.03). The
      IOL power calculations showed no significant differences among the devices, but
      the results of MAE within 0.5 D by use of Lenstar without optimization were worse
      than those of conventional methods. The AL influenced the accuracy of refractive
      outcomes determined by using Lenstar without optimization, and corneal curvature
      was shown to affect the accuracy of refractive measurements using Lenstar with
      optimization. 

PMID- 26306305
TI  - Predicting the Size of Benign Thyroid Nodules and Analysis of Associated Factors
      That Affect Nodule Size.
AB  - This study aimed to identify factors that affect the size of benign thyroid
      nodules and to predict nodule size by using a newly developed model. Because most
      thyroid nodules are benign, they are commonly only monitored. Only a few studies
      have evaluated the natural progression or regression of benign thyroid nodules.
      Large-scale studies on the subject are nonexistent. Between January 2001 and
      December 2011, our study subjects were selected from among 1,564 patients with
      benign thyroid nodules (2,469 nodules) in a retrospective analysis. We measured
      nodule size and volume and attempted to predict nodule size by using a newly
      developed model. Nodules were considered to have increased in size if the total
      volume increased by >15%. Nodules that increased in size over time required a
      longer follow-up period than nodules that decreased in size. The proportion of
      females and the cystic proportion of the nodules were relatively high in our
      study sample. For thyroid nodules that increased in size, we analyzed potential
      predictive factors. Larger nodule volume, extended follow-up period, and high
      cystic proportion were positively associated with increased nodule size.
      According to the model we developed in our study, the nodules in the group with
      an increase in size grew at an approximate rate of 0.034 cm(3) per year when
      controlled for other factors. Percutaneous ethanol injection or radiofrequency
      ablation is performed for cosmetic purposes and proper functioning if or when
      nodules reach a certain size. The model used in our study may offer helpful
      insight in determining an optimal treatment schedule for benign thyroid nodules. 

PMID- 26306306
TI  - A Case of Membranous Glomerulonephritis with Superimposed Anti-Neutrophil
      Cytoplasmic Antibody-Associated Rapidly Progressive Crescentic
      Glomerulonephritis.
AB  - Idiopathic membranous glomerulonephritis (IMGN) is commonly diagnosed in adults
      with proteinuria. Rapid deterioration of renal function is a rare complication of
      IMGN, except when accompanied by renal vein thrombosis, malignant hypertension,
      or other underlying disease, including lupus nephritis. Here, we present a case
      of rapid deterioration of renal function in a patient with MGN superimposed with
      anti-neutrophil cytoplasmic antibody (ANCA)-associated rapidly progressive
      crescentic glomerulonephritis (RPGN). Overall, about 20 cases of MGN with ANCA
      associated RPGN have been reported. This case of biopsy-proven MGN with ANCA
      associated RPGN is the first to be reported in Korea. 

PMID- 26306307
TI  - Percutaneous Forceps Retrieval of an Embolized Amplatzer Duct Occluder.
AB  - Transcatheter closure of patent ductus arteriosus with the Amplatzer duct
      occluder shows excellent results. However, there is a risk of device embolization
      after deployment. We report the case of a 33-year-old man in whom an embolized
      Amplatzer device was retrieved from the right pulmonary artery by a percutaneous
      method. We also review this uncommon severe complication and offer technical tips
      for percutaneous removal. 

PMID- 26306308
TI  - Role of Fine Needle Aspiration Cytology (FNAC) as a Diagnostic Tool in Paediatric
      Head and Neck Lymphodenopathy.
AB  - A neck mass that is present for longer than a week might be pathological
      requiring rapid and thorough evaluation. This study aims to evaluate the positive
      role Fine needle aspiration cytology plays in the diagnosis of pediatric patients
      with lymphadenopathy in the head and neck region. Fine needle aspiration of lymph
      nodes was carried out, fixed and stained by cytopathologists for 56 patients at
      the Jos University Teaching Hospital, 43 (76.8%) were inflammatory and 13 (23.2%)
      malignant. Reactive hyperplasia (72.1%), acute suppurative (18.6%) and
      tuberculosis (9.3%) constituted the inflammatory lesions. Non Hodgkins lymphoma
      was the commonest malignant lesion (76.9%) followed by Hodgkins lymphoma (15.4%),
      the least being Rhabdomyosarcoma (7.7%). Age range 10-14 years had the highest
      number of cases (46.4%). Males were 36 (64.3%) while females were 20 (35.7%). All
      malignant cases diagnosed by FNAC had to undergo confirmation/characterization by
      histology and had 100% concordance. Thus there were no false positives and
      specificity was 100%, sensitivity 100%. Of the 43 diagnosed as inflammatory by
      FNAC, 12 cases which did not resolve after treatment or where patients condition
      worsened had to undergo surgical biopsy. Out of these only 1 (8.3%) case of
      fungal infection was misdiagnosed by FNAC. The lymph nodes were generalized 4
      (7.1%) and localized in 52 (92.9%). Maximum number of cases 53 (94.6%) had
      Cervical Lymphadenopathy followed by axillary 2 (3.6%) and inguinal 1 (1.8%). Out
      of the cervical group of nodes, the upper anterior and upper posterior deep
      cervical nodes were involved in majority of cases (95%).

PMID- 26306309
TI  - Proteome-wide dataset generated by iTRAQ-3DLCMS/MS technique for studying the
      role of FerB protein in oxidative stress in Paracoccus denitrificans.
AB  - 3DLC protein- and peptide-fractionation technique combined with iTRAQ-peptide
      labeling and Orbitrap mass spectrometry was employed to quantitate Paracoccus
      dentirificans total proteome with maximal coverage. This resulted in
      identification of 24,948 peptides representing 2627 proteins (FDR<0.01) in P.
      dentirificans wild type and ferB mutant strains grown in the presence or absence
      of methyl viologen as an oxidative stressor. The data were generated for
      assessment of FerB protein role in oxidative stress as published by Pernikarova
      et al.; proteomic responses to a methyl viologen-induced oxidative stress in the
      wild type and FerB mutant strains of P. denitrificans, J. Proteomics 2015;125:68
      75. Dataset is supplied in the article. 

PMID- 26306310
TI  - Precipitation behavior in a nitride-strengthened martensitic heat resistant steel
      during hot deformation.
AB  - The stress relaxation curves for three different hot deformation processes in the
      temperature range of 750-1000  degrees C were studied to develop an understanding
      of the precipitation behavior in a nitride-strengthened martensitic heat
      resistant steel (Zhang et al., Mater. Sci. Eng. A, 2015) [1]. This data article
      provides supporting data and detailed information on how to accurately analysis
      the stress relaxation data. The statistical analysis of the stress peak curves,
      including the number of peaks, the intensity of the peaks and the integral value
      of the pumps, was carried out. Meanwhile, the XRD energy spectrum data was also
      calculated in terms of lattice distortion. 

PMID- 26306311
TI  - Comparative analysis of cerebrospinal fluid from the meningo-encephalitic stage
      of T. b. gambiense and rhodesiense sleeping sickness patients using TMT
      quantitative proteomics.
AB  - The quantitative proteomics data here reported are part of a research article
      entitled "Increased acute immune response during the meningo-encephalitic stage
      of Trypanosoma brucei rhodesiense sleeping sickness compared to Trypanosoma
      brucei gambiense", published by Tiberti et al., 2015. Transl. Proteomics 6, 1-9.
      Sleeping sickness (human African trypanosomiasis - HAT) is a deadly neglected
      tropical disease affecting mainly rural communities in sub-Saharan Africa. This
      parasitic disease is caused by the Trypanosoma brucei (T. b.) parasite, which is
      transmitted to the human host through the bite of the tse-tse fly. Two parasite
      sub-species, T. b. rhodesiense and T. b. gambiense, are responsible for two
      clinically different and geographically separated forms of sleeping sickness. The
      objective of the present study was to characterise and compare the cerebrospinal
      fluid (CSF) proteome of stage 2 (meningo-encephalitic stage) HAT patients
      suffering from T. b. gambiense or T. b. rhodesiense disease using high-throughput
      quantitative proteomics and the Tandem Mass Tag (TMT((r))) isobaric labelling. In
      order to evaluate the CSF proteome in the context of HAT pathophysiology, the
      protein dataset was then submitted to gene ontology and pathway analysis. Two
      significantly differentially expressed proteins (C-reactive protein and
      orosomucoid 1) were further verified on a larger population of patients (n=185)
      by ELISA, confirming the mass spectrometry results. By showing a predominant
      involvement of the acute immune response in rhodesiense HAT, the proteomics
      results obtained in this work will contribute to further understand the
      mechanisms of pathology occurring in HAT and to propose new biomarkers of
      potential clinical utility. The mass spectrometry raw data are available in the
      Pride Archive via ProteomeXchange through the identifier PXD001082. 

PMID- 26306312
TI  - The proteome of the outer membrane vesicles of an Antarctic bacterium Pseudomonas
      syringae Lz4W.
AB  - Outer membrane vesicles (OMVs) of gram-negative bacteria are released during all
      growth phases and play an important role in bacterial physiology. They consist of
      lipids, proteins, lipopolysaccharides and other molecules. The OMVs of the
      Antarctic bacterium Pseudomonas syringae Lz 4W were isolated and identified their
      proteins. The mass spectral data set deposited with PRIDE, accession number PXD
      000221 is presented in this report. The proteins identified from the OMVs of P.
      syringae Lz4W, data of this study were published in the Journal of proteome
      research [1]. 

PMID- 26306313
TI  - A comparison of flexural strengths of polymer (SBR and PVA) modified, roller
      compacted concrete.
AB  - This brief article aims to reveal the flexural performance, including the
      equivalent flexural strength of PVA (Polyvinyl Alcohol) modified concrete by
      comparing it primarily with that of SBR (Styrene Butadiene Rubber) concrete. This
      data article is directly related to Karadelis and Lin [6]. 

PMID- 26306314
TI  - Data set for the proteomic inventory and quantitative analysis of chicken
      eggshell matrix proteins during the primary events of eggshell mineralization and
      the active growth phase of calcification.
AB  - Chicken eggshell is a biomineral composed of 95% calcite calcium carbonate
      mineral and of 3.5% organic matrix proteins. The assembly of mineral and its
      structural organization is controlled by its organic matrix. In a recent study
      [1], we have used quantitative proteomic, bioinformatic and functional analyses
      to explore the distribution of 216 eggshell matrix proteins at four key stages of
      shell mineralization defined as: (1) widespread deposition of amorphous calcium
      carbonate (ACC), (2) ACC transformation into crystalline calcite aggregates, (3)
      formation of larger calcite crystal units and (4) rapid growth of calcite as
      columnar structure with preferential crystal orientation. The current article
      detailed the quantitative analysis performed at the four stages of shell
      mineralization to determine the proteins which are the most abundant.
      Additionally, we reported the enriched GO terms and described the presence of 35
      antimicrobial proteins equally distributed at all stages to keep the egg free of
      bacteria and of 81 proteins, the function of which could not be ascribed. 

PMID- 26306315
TI  - Data in support of effects of cell-cell contact and oxygen tension on
      chondrogenic differentiation of stem cells.
AB  - This paper presents data related to the research article entitled "Effects of
      cell-cell contact and oxygen tension on chondrogenic differentiation of stem
      cells" [1]. Three sets of micropatterns were fabricated to study the influence of
      the cell-cell contact on the chondrogenic induction of mesenchymal stem cells
      (MSCs). The basic repeat units of these micropatterns were of the same area and
      microisland number to guarantee the same cell density in each culture well. Cells
      on these micropatterns experienced the same microenvironment except cell-cell
      contact extent. Immunofluorescent staining and quantitative real-time polymerase
      chain reaction (qRT-PCR) were performed, and the data are included here. 

PMID- 26306316
TI  - Altering adsorbed proteins or cellular gene expression in bone-metastatic cancer
      cells affects PTHrP and Gli2 without altering cell growth.
AB  - The contents of this data in brief are related to the article titled "Matrix
      Rigidity Regulates the Transition of Tumor Cells to a Bone-Destructive Phenotype
      through Integrin beta3 and TGF-beta Receptor Type II". In this DIB we will
      present our supplemental data investigating Integrin expression, attachment of
      cells to various adhesion molecules, and changes in gene expression in multiple
      cancer cell lines. Since the interactions of Integrins with adsorbed matrix
      proteins are thought to affect the ability of cancer cells to interact with their
      underlying substrates, we examined the expression of Integrin beta1, beta3, and
      beta5 in response to matrix rigidity. We found that only Ibeta3 increased with
      increasing substrate modulus. While it was shown that fibronectin greatly affects
      the expression of tumor-produced factors associated with bone destruction
      (parathyroid hormone-related protein, PTHrP, and Gli2), poly-l-lysine,
      vitronectin and type I collagen were also analyzed as potential matrix proteins.
      Each of the proteins was independently adsorbed on both rigid and compliant
      polyurethane films which were subsequently used to culture cancer cells. Poly-l
      lysine, vitronectin and type I collagen all had negligible effects on PTHrP or
      Gli2 expression, but fibronectin was shown to have a dose dependent effect.
      Finally, altering the expression of Ibeta3 demonstrated that it is required for
      tumor cells to respond to the rigidity of the matrix, but does not affect other
      cell growth or viability. Together these data support the data presented in our
      manuscript to show that the rigidity of bone drives Integrinbeta3/TGF-beta
      crosstalk, leading to increased expression of Gli2 and PTHrP. 

PMID- 26306317
TI  - Data of high performance precast external walls for warm climate.
AB  - The data given in the following paper are related to input and output information
      of the paper entitled Design method of high performance precast external walls
      for warm climate by multi-objective optimization analysis by Baglivo et al. [1].
      Previous studies demonstrate that the superficial mass and the internal areal
      heat capacity are necessary to reach the best performances for the envelope of
      the Zero Energy Buildings located in a warm climate [2-4]. The results show that
      it is possible to achieve high performance precast walls also with light and
      ultra-thin solutions. A multi-criteria optimization has been performed in terms
      of steady and dynamic thermal behavior, eco sustainability score and costs. The
      modeFRONTIER optimization tool, with the use of computational procedures
      developed in Matlab, has been used to assess the thermal dynamics of building
      components. A large set of the best configurations of precast external walls for
      warm climate with their physical and thermal properties have been reported in the
      data article. 

PMID- 26306318
TI  - Quantitative proteomics unravels that the post-transcriptional regulator Crc
      modulates the generation of vesicles and secreted virulence determinants of
      Pseudomonas aeruginosa.
AB  - Crc is a post-transcriptional regulator in Pseudomonas aeruginosa that modulates
      its metabolism, but also its susceptibility to antibiotics and virulence. Most of
      P. aeruginosa virulence factors are secreted or engulfed in vesicles. A Crc
      deficient mutant was created and the extracellular vesicles associated
      exoproteome and the vesicle-free secretome was quantified using iTRAQ. Fifty
      vesicles-associated proteins were more abundant and 14 less abundant in the Crc
      defective strain, whereas 37 were more abundant and 17 less abundant in the
      vesicle-free secretome. Different virulence determinants, such as ToxA, protease
      IV, azurin, chitin-binding protein, PlcB and Hcp1, were less abundant in the Crc
      defective mutant. We also observed that the crc mutant presented an impaired
      vesicle-associated secretion of quorum sensing signal molecules and less
      cytotoxicity than its wild-type strain, in agreement with the low secretion of
      proteins related to virulence. Our results offer new insights into the mechanisms
      by which Crc regulates P. aeruginosa virulence, through the modulation of vesicle
      formation and secretion of both virulence determinants and quorum sensing
      signals. 

PMID- 26306319
TI  - Experimental data in support of continuous microwave effect on emulsion
      polymerization of styrene.
AB  - This article contains original experimental data, figures and methods to the
      study of Microwave-assisted emulsion polymerization of styrene under the frame of
      "Enhanced Microwave Synthesis" (EMS), has been examined to investigate the
      advantages of Microwave (MW) power use in emulsion polymerization (Ergan et al.,
      Eur. Polym. J. 69, 2015, 374-384). For comparative purpose, MW and conventional
      heating (CH) method experiments were conducted under similar conditions. By
      externally cooling the reaction vessel with 1,4-dioxane, constant and continuous
      MW power was successfully applied at isothermal condition during the
      polymerization. Here we give the MW power calibration data of MW-experimental
      system, the complete set of the experimental polymerization data and the analysis
      data obtained from different polymer characterization test devices (GPC, DSC and
      Viscometer). 

PMID- 26306320
TI  - Mass spectrometry identification of age-associated proteins from the malaria
      mosquitoes Anopheles gambiae s.s. and Anopheles stephensi.
AB  - This study investigated proteomic changes occurring in Anopheles gambiae and
      Anopheles stephensi during adult mosquito aging. These changes were evaluated
      using two-dimensional difference gel electrophoresis (2D-DIGE) and the identities
      of aging related proteins were determined using capillary high-pressure liquid
      chromatography (capHPLC) coupled with a linear ion-trap (LTQ)-Orbitrap XL hybrid
      mass spectrometry (MS). Here, we have described the techniques used to determine
      age associated proteomic changes occurring in heads and thoraces across three age
      groups; 1, 9 and 17 d old A. gambiae and 4 age groups; 1, 9, 17 and 34 d old A.
      stephensi. We have provided normalised spot volume raw data for all protein spots
      that were visible on 2D-DIGE images for both species and processed Orbitrap mass
      spectrometry data. For public access, mass spectrometry raw data are available
      via ProteomeXchange with identifier PXD002153. A detailed description of this
      study has been described elsewhere [1]. 

PMID- 26306321
TI  - Data for comparative proteomics analysis of the antitumor effect of CIGB-552
      peptide in HT-29 colon adenocarcinoma cells.
AB  - CIGB-552 is a second generation antitumor peptide that displays potent
      cytotoxicity in lung and colon cancer cells. The nuclear subproteome of HT-29
      colon adenocarcinoma cells treated with CIGB-552 peptide was identified and
      analyzed [1]. This data article provides supporting evidence for the above
      analysis. 

PMID- 26306322
TI  - Data in support of the mutagenic potential of the isoflavone irilone in cultured
      V79 cells.
AB  - The isoflavone irilone is found in human plasma after ingestion of red clover
      based dietary supplements, but information allowing safety assessment is rare.
      Here, data in support of the mutagenic potential of irilone in cultured V79 cells
      [1] are presented. These data include (i) a quantitative assessment of irilone in
      the culture medium during the cell culture experiments, (ii) changes in the
      mutation spectrum in cDNA of the hypoxanthine-guanine phosphoribosyltransferase
      locus of irilone-treated V79 cells, (iii) occurrence of karyorrhexis and
      apoptosis as well as (iv) number of micronucleated cells containing whole
      chromosomes or chromosomal fragments. Also exemplary micrographs, used for the
      fluorescence microscopic assessment of (iii) and (iv) are presented. 

PMID- 26306323
TI  - Identification of Drosophila centromere associated proteins by quantitative
      affinity purification-mass spectrometry.
AB  - Centromeres of higher eukaryotes are epigenetically defined by the centromere
      specific histone H3 variant CENP-A(CID). CENP-A(CID) builds the foundation for
      the assembly of a large network of proteins. In contrast to mammalian systems,
      the protein composition of Drosophila centromeres has not been comprehensively
      investigated. Here we describe the proteome of Drosophila melanogaster
      centromeres as analyzed by quantitative affinity purification-mass spectrometry
      (AP-MS). The AP-MS input chromatin material was prepared from D. melanogaster
      cell lines expressing CENP-A(CID) or H3.3 fused to EGFP as baits. Centromere
      chromatin enriched proteins were identified based on their relative abundance in
      CENP-A(CID)-GFP compared to H3.3-GFP or mock affinity-purifications. The analysis
      yielded 86 proteins specifically enriched in centromere chromatin preparations.
      The data accompanying the manuscript on this approach (Barth et al., 2015,
      Proteomics 14:2167-78, DOI: 10.1002/pmic.201400052) has been deposited to the
      ProteomeXchange Consortium (http://www.proteomexchange.org) via the PRIDE partner
      repository with the dataset identifier PXD000758. 

PMID- 26306324
TI  - Data supporting chitosan facilitates structure formation of the salivary gland by
      regulating the basement membrane components.
AB  - To investigate the role of basement membrane (BM) in chitosan-mediated
      morphogenesis of the salivary glands, the embryonic submandibular gland (SMG)
      experimental model was used. Chitosan promotes branching at distinct stages in
      SMG morphogenesis. When enzymes such as type IV collagenase, dispase, and
      cathepsin B were used to digest the BM components, the morphogenetic effect
      mediated by chitosan disappeared. Immunofluorescence revealed that the
      corresponding receptors for BM components, including CD49c, CD49f, CD29, and
      dystroglycan, were locally enriched at the epithelial-mesenchymal junction around
      BM areas. The functional roles of laminin alpha1 and alpha5 in SMG branching were
      explored via siRNA knockdown, and suppression was confirmed at both the RNA and
      protein levels (Yang and Hsiao, Biomaterials,
      http://dx.doi.org/10.1016/j.biomaterials.2015.06.028, 2015). This data article
      demonstrates the experimental approaches to investigate the role of basement
      membrane in the structure formation of the salivary gland engineered by
      biomaterials. 

PMID- 26306325
TI  - A human gut metaproteomic dataset from stool samples pretreated or not by
      differential centrifugation.
AB  - We present a human gut metaproteomic dataset deposited in the ProteomeXchange
      Consortium via the PRIDE partner repository with the dataset identifier
      PXD001573. Ten aliquots of a single stool sample collected from a healthy human
      volunteer were either pretreated by differential centrifugation (DC; N=5) or not
      centrifuged (NC; N=5). Protein extracts were then processed by filter-aided
      sample preparation, single-run liquid chromatography and high-resolution mass
      spectrometry, and peptide identification was carried out using Sequest-HT as
      search engine within the Proteome Discoverer informatic platform. The dataset
      described here is also related to the research article entitled "Enrichment or
      depletion? The impact of stool pretreatment on metaproteomic characterization of
      the human gut microbiota" published in Proteomics (Tanca et al., 2015), [1]. 

PMID- 26306327
TI  - Reward Deficiency Syndrome: Attentional/Arousal Subtypes, Limitations of Current
      Diagnostic Nosology, and Future Research.
AB  - We theorise that in some cases Attention Deficit Hyperactivity Disorder (ADHD)
      predisposes to narcolepsy and hypersomnia, and that there may be a shared
      pathophysiology with various addictions [Reward Deficiency Syndrome (RDS)].
      Reticence to acknowledge such connections may be due to a narrow nosological
      framework. Additionally, we theorise that the development of narcolepsy on a
      baseline of ADHD/RDS leads to an additional assault on the dopaminergic reward
      system in such individuals. In this study, we propose to test these hypotheses by
      using a combination of broad genetic screening, and neuroimaging with and without
      pharmacological intervention, in those with pure ADHD, pure narcolepsy, and the
      combined ADHD-narcolepsy phenotype. Results of this proposed study may reveal a
      common pathophysiology of ADHD, narcolepsy and RDS, and perhaps an additional
      compromise to the reward system in those with combined ADHD-narcolepsy. If the
      evidence supports the hypothesis that indeed there is a shared pathophysiology
      for narcolepsy with RDS and thus its subtype ADHD, early
      intervention/preventative treatment amongst those with ADHD may be beneficial
      with the putative dopaminergic compound KB220ZTM.

PMID- 26306326
TI  - Neuroenhancement of Exposure Therapy in Anxiety Disorders.
AB  - Although exposure-based treatments and anxiolytic medications are more effective
      than placebo for treating anxiety disorders, there is still considerable room for
      further improvement. Interestingly, combining these two modalities is usually not
      more effective than the monotherapies. Recent translational research has
      identified a number of novel approaches for treating anxiety disorders using
      agents that serve as neuroenhancers (also known as cognitive enhancers). Several
      of these agents have been studied to determine their efficacy at improving
      treatment outcome for patients with anxiety and other psychiatric disorders. In
      this review, we examine d-cycloserine, yohimbine, cortisol, catecholamines,
      oxytocin, modafinil, and nutrients such as caffeine and amino fatty acids as
      potential neuroenhancers. Of these agents, d-cycloserine shows the most promise
      as an effective neuroenhancer for extinction learning and exposure therapy. Yet,
      the optimal dosing and dose timing for drug administration remains uncertain.
      There is partial support for cortisol, catecholamines, yohimbine and oxytocin for
      improving extinction learning and exposure therapy. There is less evidence to
      indicate that modafinil and nutrients such as caffeine and amino fatty acids are
      effective neuroenhancers. More research is needed to determine their long term
      efficacy and clinical utility of these agents.

PMID- 26306328
TI  - Enhancing Brain Pregnenolone May Protect Cannabis Intoxication but Should Not Be
      Considered as an Anti-addiction Therapeutic: Hypothesizing Dopaminergic Blockade
      and Promoting Anti-Reward.
AB  - Many US states now embrace the medical and recreational use of Cannabis. Changes
      in the laws have heightened interest and encouraged research into both
      cannabinoid products and the potential harms of Cannabis use, addiction, and
      intoxication. Some research into those harms will be reviewed here and misgivings
      about the use of Pregnenolone, to treat cannabis addiction and intoxication
      explained. Pregnenolone considered the inactive precursor of all steroid
      hormones, has recently been shown to protect the brain from Cannabis
      intoxication. The major active ingredient of Cannabis sativa (marijuana), Delta9
      tetrahydrocannabinol (THC) enhances Pregnenolone synthesis in the brain via
      stimulation of the type-1 cannabinoid (CB1) receptor. This steroid has been shown
      to inhibit the activity of the CB1 receptor thereby reducing many of the effects
      of THC. While this mechanism seems correct, in our opinion, Vallee et al.,
      incorrectly suggest that blocking CB1 receptors could open unforeseen approaches
      to the treatment of cannabis intoxication and addiction. In this hypothesis, we
      caution the scientific community that, other CB1 receptor blockers, such as,
      Rimonabant (SR141718) have been pulled off the market in Europe. In addition, CB1
      receptor blockers were rejected by the FDA due to mood changes including suicide
      ideation. Blocking CB1 receptors would result in reduced neuronal release of
      Dopamine by disinhibition of GABA signaling. Long-term blockade of cannabinoid
      receptors could occur with raising Pregnenolone brain levels, may induce a
      hypodopaminergic state, and lead to aberrant substance and non-substance
      (behavioral) addictions.

PMID- 26306330
TI  - So How Good are These Smartphone Sound Measurement Apps?

PMID- 26306331
TI  - Eligibility for home oxygen programs and funding across Canada.
AB  - BACKGROUND: In Canada, although medical insurance is generally universal,
      significant differences exist in the provision of home oxygen therapy across the
      country. OBJECTIVE: To systematically compare the terms of reference for home
      oxygen across Canada, with a focus on the clinical inclusion criteria to the
      programs. METHODS: The authors searched the terms of reference of the 10 Canadian
      provinces and three territories, focusing on general eligibility criteria for
      home oxygen (including blood gas criteria, and eligibility criteria for
      ambulatory and nocturnal oxygen), and compared the eligibility criteria to the
      widely accepted criteria of the Nocturnal Oxygen Therapy Trial (NOTT) trial, the
      clinical recommendations of the Canadian Thoracic Society and the results of
      Cochrane reviews. RESULTS: The terms of reference for nine provinces were
      retrieved. All jurisdictions have similar criteria for long-term oxygen therapy,
      with slight differences in the thresholds of prescription and the clinical
      criteria defining 'pulmonary hypertension' or 'cor pulmonale'. The use of
      oxyhemoglobin saturation as a criterion for funding is inconsistent. All nine
      provinces fund nocturnal oxygen, all with different clinical criteria. Funding
      for portable oxygen widely varies across provinces, whether the ambulatory
      equipment is offered to patients on long-term oxygen therapy or to those who have
      isolated exercise-induced desaturation. The terms of reimbursement are very
      heterogeneous. CONCLUSIONS: Heterogeneity exists in the criteria for eligibility
      to home oxygen programs and funding across Canada. Terms of prescription and
      reimbursement of oxygen are not necessarily supported by available evidence from
      the current literature in several Canadian jurisdictions.

PMID- 26306332
TI  - Efficacy of Florfenicol for Control of Mortality Associated with Edwardsiella
      ictaluri in Three Species of Catfish.
AB  - The efficacy of florfenicol for control of mortality associated with Edwardsiella
      icatluri was studied in fingerlings of Channel Catfish Ictalurus puntatus (Delta
      strain), Blue Catfish I. furcatus (D&B strain), and a hybrid catfish (Delta
      strain Channel Catfish * D&B strain Blue Catfish). On day 0, fish were immersion
      challenged in 65-L aquaria. For each of the three species of catfish, 10 aquaria
      were randomly assigned to two treatment groups, either treated with florfenicol
      at 0 mg/kg of body weight (unmedicated feed) or at 10 mg/kg (medicated feed).
      Fish were treated for 10 consecutive days, monitored for mortality during this
      treatment period, and observed for 14 d afterwards. Post observation, all
      survivors were humanely euthanized in tricaine methanesulfonate, cultured for E.
      ictaluri, and examined for gross pathology. The mean cumulative percent mortality
      from enteric septicemia of catfish (ESC) challenge among the three genotypes of
      catfish did not differ between Blue Catfish, hybrid, and Channel Catfish in
      treated or control groups. However, the florfenicol-treated fish had a
      significantly lower mean cumulative mortality (6%) than the controls (78%). All
      genotypes of catfish tested were responsive to treatment with florfenicol
      medicated feed for control of mortality associated with ESC. There were no
      significant differences in mortality associated with hybrid catfish, blue
      catfish, and Channel Catfish (Delta strain).

PMID- 26306333
TI  - Assessment of the Long-Term Viability of the Myxospores of Myxobolus cerebralis
      as Determined by Production of the actinospores by Tubifex tubifex.
AB  - While whirling disease was first observed in Rainbow Trout Oncorhynchus mykiss in
      1893, the complete life cycle of Myxobolus cerebralis (Mc), the causative agent
      of the disease, was not understood until 1984, when it was shown to involve two
      obligate hosts, a salmonid fish and the aquatic oligochaete Tubifex tubifex (Tt).
      The viability of the triactinomyxon (TAM) actinospores produced by Tt has been
      well studied, and is known to be temperature dependent and measured in days and
      weeks. Assertions that Mc myxospores produced by infected fish remain viable for
      years or even decades were made during the mid-20th century, decades before the
      Mc life cycle was described. Moreover, the duration of myxospore viability has
      not been well studied since the life cycle was elucidated. In a series of time
      delay treatments, we assessed the long-term viability of Mc myxospores by
      exposure to Mc-susceptible Tt oligochaetes and quantified TAM production. As the
      time delay between inoculation and incubation of Mc myxospores in sand and water
      and exposure to Tt oligochaetes increased, TAM production decreased
      exponentially. Production among the 15-d time-delay replicates was reduced 74.7%
      compared with the 0-d treatment. Likewise, total TAM production was reduced 94.5,
      99.4, and 99.9%, respectively, in the 90-, 120-, and 180-d time-delay treatments.
      Linear regression analysis of our data and the absence of TAM production among
      replicates of Mc myxospores held at 5 degrees C for 365 d prior to exposure to Mc
      susceptible Tt oligochaetes indicate that the long-term viability of Mc
      myxospores is less than 1 year under the conditions of this study.

PMID- 26306334
TI  - The Impact of Egg Ozonation on Hatching Success, Larval Growth, and Survival of
      Atlantic Cod, Atlantic Salmon, and Rainbow Trout.
AB  - The direct exposure of fish eggs to ozonated water has generated interest as a
      means of ensuring pathogen-free eggs without the use of harsh chemicals. However,
      there are numerous knowledge gaps, including safe contact times, exposure levels,
      and potential long-term effects on aquaculture species in both freshwater and
      seawater. The effect of different ozone (O3) doses (0.5-1.0, 1.5-2.0, and 2.5-3.0
      mg of O3/L for 90 s) on recently fertilized eggs of Atlantic Cod Gadus morhua and
      eyed eggs of Atlantic Salmon Salmo salar and Rainbow Trout Oncorhynchus mykiss
      was evaluated in comparison with the effects of two commercial disinfectants:
      Perosan (0.004 mg/L) and Ovadine (100 mg/L). The impact of ozone application was
      evaluated based on hatching success, larval nucleic acid concentration, larval
      growth, and survival. Overall, results indicated that ozonation of Atlantic Cod
      eggs at a dose less than 3.0 mg/L for 90 s produced no negative effect on the
      larvae up to 30 d posthatch. Furthermore, ozonation of Atlantic Salmon and
      Rainbow Trout eggs generated no negative effect on the larvae, based on
      monitoring until 85% yolk sac re-absorption (16 d posthatch).

PMID- 26306335
TI  - Commentary on Troedsson's 1964 article "Stump arterial circulation and its
      relationship to the prescription of a prosthesis for the geriatric patient".

PMID- 26306329
TI  - The Molecular Neurobiology of Twelve Steps Program & Fellowship: Connecting the
      Dots for Recovery.
AB  - There are some who suggest that alcoholism and drug abuse are not diseases at all
      and that they are not consequences of a brain disorder as espoused recently by
      the American Society of Addiction Medicine (ASAM). Some would argue that addicts
      can quit on their own and moderate their alcohol and drug intake. When they
      present to a treatment program or enter the 12 Step Program & Fellowship, many
      addicts finally achieve complete abstinence. However, when controlled drinking
      fails, there may be successful alternatives that fit particular groups of
      individuals. In this expert opinion, we attempt to identify personal differences
      in recovery, by clarifying the molecular neurobiological basis of each step of
      the 12 Step Program. We explore the impact that the molecular neurobiological
      basis of the 12 steps can have on Reward Deficiency Syndrome (RDS) despite
      addiction risk gene polymorphisms. This exploration has already been accomplished
      in part by Blum and others in a 2013 Springer Neuroscience Brief. The purpose of
      this expert opinion is to briefly, outline the molecular neurobiological and
      genetic links, especially as they relate to the role of epigenetic changes that
      are possible in individuals who regularly attend AA meetings. It begs the
      question as to whether "12 steps programs and fellowship" does induce
      neuroplasticity and continued dopamine D2 receptor proliferation despite carrying
      hypodopaminergic type polymorphisms such as DRD2 A1 allele. "Like-minded" doctors
      of ASAM are cognizant that patients in treatment without the "psycho-social
      spiritual trio," may not be obtaining the important benefits afforded by adopting
      12-step doctrines. Are we better off with coupling medical assisted treatment
      (MAT) that favors combining dopamine agonist modalities (DAM) as possible histone
      deacetylase activators with the 12 steps followed by a program that embraces
      either one or the other? While there are many unanswered questions, at least we
      have reached a time when "science meets recovery," and in doing so, can further
      redeem joy in recovery.

PMID- 26306338
TI  - Discharge planning at   the bedside.

PMID- 26306337
TI  - Re "The Electronic Health Record".

PMID- 26306339
TI  - Evidence for chromosomal macronuclear substructures in Tetrahymena.
AB  - Under the growth conditions employed, the G1 macronucleus of Tetrahymena
      pyriformis HSM contains 7.4 * 10(-12) g DNA, the G2 micronucleus 0.42 * 10(-12)
      g. DNA content from the Tetrahymena thermophila macronucleus did not
      significantly differ from that of HSM, but the micronucleus contained about twice
      as much DNA as the micronucleus of the HSM cells. The T. thermophila macronucleus
      contained on average enough DNA for ~ 35 haploid micronuclear copies. A new
      spreading technic allowed separation of macronuclear substructures from cells of
      late G2 to early G1. Photometric determination of DNA content of 345 individual
      structures suggested the existence of 5 different-sized macronuclear structures
      with a DNA content corresponding to 2, 4, 8, and 16 * the basic values.
      Comparison of the DNA content of these structures with (a) mitotic micronuclear
      chromosomes and (b) meiotic micronuclear chromosomes of T. thermophila cells
      suggests that the 5 basic values of macronuclear structures derive from
      structures of micronuclear chromosomes. The micronuclear chromosomes of T.
      pyriformis may be oligotenic. It is suggested that these results further our
      understanding of macronuclear organization.

PMID- 26306341
TI  - Findings of research misconduct.

PMID- 26306342
TI  - Understanding emergency information management.

PMID- 26306340
TI  - Findings of research misconduct.

PMID- 26306343
TI  - Leadership.

PMID- 26306344
TI  - Author, Beware! A Look at the Dangers of Predatory Publishing.

PMID- 26306345
TI  - Bathing Disability and Bathing Persons with Dementia.
AB  - Bathing disability, evidence of functional decline, predicts admission to long
      term care facilities following acute care hospitalizations. Nurses are challenged
      to assess bathing disability in hospitalized older persons and those with
      dementia to support their maximal functional performance and implement diverse
      bathing strategies.

PMID- 26306346
TI  - Delirium: Why Are Nurses Confused?
AB  - Nurses have a key role in detection of delirium, yet this condition remains under
      recognized and poorly managed. The aim of this study was to explore nurses'
      knowledge of delirium-related information as well as their perception of their
      level of knowledge.

PMID- 26306347
TI  - Anemic Control in Patients with Chronic Kidney Disease: A Controversial Issue.
AB  - Anemia in chronic kidney disease doubles the risk of death and leads to many
      complications. Management includes erythropoietin-stimulating agent therapy,
      treatment of iron deficiency, patient education, and collaboration with the
      multidisciplinary team.

PMID- 26306348
TI  - Preventing Progression of Post-Thrombotic Syndrome for Patients Post-Deep Vein
      Thrombosis.
AB  - Post-thrombotic syndrome is a chronic condition that develops in up to 50% of
      patients with acute deep vein thrombosis. Its burden includes increased costs,
      decreased quality of life, and decreased personal productivity.

PMID- 26306349
TI  - Does Associate Degree Curricula Adequately Prepare Nurses for Leadership Roles?

PMID- 26306350
TI  - Nutrition to improve outcome. Supplements to Promote Wound Healing.

PMID- 26306351
TI  - Ethics and Undertreatment of Pain in Patients with a History of Drug Abuse.
AB  - Patients with substance abuse history make up 14% of inpatient admissions to
      acute care units, where it has been reported a great deal of patient pain is
      unrelieved (Substance Abuse and Mental Health Service Administration [SAMHSA],
      2009. Definitions of substance abuse terms including tolerance, dependence,
      addiction, and pseudoaddiction are essential to a nurse's understanding of pain
      medication administration in patients with substance abuse history. Pain
      management is one of the nurse's main responsibilities, and using the principles
      of autonomy, beneficence, nonmaleficence, and justice can guide the nurse to
      making appropriate pain management decisions for and with these patients. Nursing
      implications and resources for more information are discussed.

PMID- 26306352
TI  - Educational Planning for Establishing a Health-Promoting Workplace (HPW).
AB  - The Academy of Medical-Surgical Nurses (AMSN) has had an ongoing series of
      articles related to Healthy Practice Environments. The AMSN website
      (www.amsn.org) also has a number of articles and documents about initiatives that
      AMSN has undertaken to promote healthy practice environments in health care
      settings. This articles will focus on the educational work necessary for nurses
      who desire to increase the healthiness of their workplace. The work is not easy,
      but the end result could be one that leaves a lasting legacy for those who work
      in that environment.

PMID- 26306353
TI  - Legally: What is Quality Care? Understanding Nursing Standards.

PMID- 26306355
TI  - Clinical Partners' Perceptions of Patient Assignments According to Acuity.
AB  - Clinical partners (CPs) experienced disproportionate workloads related to
      patients' levels of acuity. This problem was addressed on a medical-surgical unit
      by developing patient acuity ratings and equitable acuity assignments for the
      CPs.

PMID- 26306354
TI  - Breathing Exercises for Inpatients with Sickle Cell Disease.
AB  - Sickle cell disease (SCD) is a painful condition wherein breathing often is
      compromised. This pilot study supports the premise that individuals with SCD are
      willing to learn breathing exercises. Medical-surgical nurses should encourage
      breathing exercises for managing pain and preventing complications.

PMID- 26306356
TI  - Recognizing Prescription Drug Abuse and Addiction in Patients, Part II .
AB  - With health and wellness advocacy as a part of their role, medical-surgical
      nurses should do their best to address patients' hidden health care concerns such
      as drug misuse and abuse, and lead them to treatment resources. By gaining
      knowledge of prescription drug abuse and misuse, nurses will be more prepared to
      recognize these problems in their patients.

PMID- 26306357
TI  - Can Rounding Reduce Patient Falls in Acute Care? An Integrative Literature
      Review.
AB  - Falls are a leading cause of nonfatal injuries and trauma-related
      hospitalizations in the United States, and have been linked directly with the
      quality of nursing care in the hospital setting. In this literature review,
      multiple studies are summarized that found rounding decreased falls per 1,000
      patient days.

PMID- 26306358
TI  - Voluntary Stopping of Eating and Drinking: An Ethical Alternative to Physician
      Assisted Suicide.

PMID- 26306359
TI  - Evaluation Research.

PMID- 26306360
TI  - The Ethical Use of Social Media in Nursing Practice.

PMID- 26306361
TI  - Mustang Nurse.

PMID- 26306362
TI  - Ethical Practice, Quality Care.

PMID- 26306363
TI  - Self-Care as a Matter of Ethics and Professionalism.

PMID- 26306364
TI  - A Decision Tree Model for Postoperative Pain Management.
AB  - Postoperative pain management involves many factors. Current information
      regarding assessment and treatment of postoperative pain is discussed. A decision
      tree model flowchart was developed based on patient characteristics, co
      morbidities, and the type of pain.

PMID- 26306365
TI  - A Patient with Pulmonary Hypertension on a Medical-Surgical Unit.
AB  - The medical-surgical nurse is positioned to provide safe, clinical care to
      patients with pulmonary hypertension (PH). An-overview of the pathophysiology,
      diagnostic studies, and treatments associated with PH is described.

PMID- 26306366
TI  - Computer Vision Syndrome: A Review of Literature.
AB  - Computer vision syndrome is caused by prolonged computer use. Symptoms,
      treatments, and recommendations are discussed.

PMID- 26306367
TI  - Oral Anticoagulants and Atrial Fibrillation: An Update for the Clinical Nurse.
AB  - Anticoagulation is an important strategy for the prevention of stroke associated
      with atrial fibrillation. Development of new oral agents has created a need to
      educate nurses to administer these medications and provide patient education.

PMID- 26306368
TI  - Low-Income Cancer Survivors' Use of Health-Promoting Behaviors.
AB  - This cross-sectional correlation study examined use of health-promoting (HP)
      behaviors and self-efficacy for engaging in HP behaviors. Participants reported
      higher HP behavior scores for health responsibility, interpersonal relationships,
      and spiritual growth, and lower scores for physical activity/exercise, nutrition,
      and stress management. Low physical activity, stress management, and nutrition
      scores suggest nurses can implement strategies that encourage use of these HP
      behaviors and enhance self-efficacy.

PMID- 26306369
TI  - Nurturing New Hires to Safe Practices.

PMID- 26306370
TI  - Nutrition to Improve Outcomes. What YOU Told Us.

PMID- 26306371
TI  - Patient and Family Engagement: A Global Initiative.

PMID- 26306372
TI  - The Effects of Nurse Staffing on Quality of Care.

PMID- 26306373
TI  - Current Trends in Stress Management.

PMID- 26306374
TI  - Sustaining the Human Experience in a High Tech Environment: EMR Implementation.
AB  - Utilizing standardized terminology within the electronic medical record (EMR) is
      critical for nurses to communicate their contact on patient care. The widespread
      requirement for quality, efficiency, and cost containment has made it imperative
      to express nursing knowledge in a meaningful way to be shared across the care
      continuum. Utilizing an electronic record gives each health care provider the
      ability to review the patient's care across the continuum, avoiding the
      possibility of duplication of services. This will assist in improving treatment
      efficiencies and reducing costs per procedure or treatment. The documentation of
      care using an electronic medical record demonstrates the impact of nursing on
      patient care and validates the significance of nursing practice. Valuable time is
      spent with the patient while utilizing the EMR as a functional tool. Patient
      interactions are enhanced as the EMR assists in involving the patients and their
      significant others in the treatment plan.

PMID- 26306375
TI  - Biofilm as the Cause of Non-Healing Wounds.

PMID- 26306376
TI  - Nurses as Champions for Patient Safety and Interdisciplinary Problem Solving.
AB  - Nurses on an inpatient surgical unit were apprehensive in activating the Rapid
      Response Team (RRT). Nurse-led interdisciplinary solutions addressed perceived
      barriers and led to open communication and issue resolution with physician
      colleagues.

PMID- 26306377
TI  - Living in the Everydayness of HIV Infection: Experiences of Young African
      American Women.
AB  - The purpose of this Heideggerian phenomenological study was to explore the lived
      experiences, including spiritual and self-care practices, of young African
      American women infected with the human immunodeficiency virus. One theme, "Living
      in the Everydayness of HIV" and implications for nurses will be discussed.

PMID- 26306378
TI  - Life-Worlds in Phenomenology.

PMID- 26306379
TI  - Tracheostomy: Site Care, Suctioning, and Readiness.

PMID- 26306381
TI  - Managing the 80/20 Rule.

PMID- 26306380
TI  - Metabolic Syndrome.

PMID- 26306382
TI  - Teaching Patients with Hearing Loss.

PMID- 26306383
TI  - The Computer Will Not Give Me the Information I Need: A Quality Method to
      Intervene.

PMID- 26306384
TI  - [The Epidemiology of Gastric Cancer: The Hisayama Study].

PMID- 26306385
TI  - [An Autopsy Case of Abnormal Behaviour Induced by Zolpidem].
AB  - Zolpidem is a widely used ultrashort-acting non-benzodiazepine in clinical
      practice; compared with benzodiazepines, it does not have side effects such as
      daytime hangover, rebound insomnia, and development of tolerance. We report an
      autopsy case of abnormal behaviour induced by zolpidem. A man in his 60's had
      suffered from postherpetic neuralgia about 2 months ago and had been prescribed
      zolpidem for insomnia. According to his family, he had no memory of his actions
      such as striking a wall, taking his futon outside, and eating 5 times a day after
      he took zolpidem. Because his postherpetic neuralgia did not improve, he was
      hospitalized and treated with an epidural block. During hospitalization, he took
      off his clothes, removed the epidural block catheter by himself, and slept on
      others' beds. He disappeared from the hospital one day; the next day, he was
      found dead in a narrow water storage tank 10 km away from the hospital. He was
      thought to have driven a car by himself to reach the place. Forensic autopsy
      revealed that the cause of death was drowning. Zolpidem and several other drugs
      were detected by toxicological analysis of his blood; the concentrations of these
      drugs were within therapeutic range. There are several reports about somnambulism
      induced by zolpidem such as sleepwalking, sleep driving, and eating. Considering
      the strange episodes following zolpidem administration, his behaviour on the day
      of his death was considered abnormal behaviour induced by zolpidem.

PMID- 26306386
TI  - Avulsion Fracture of the Tibial Tuberosity Requiring Meniscal Repair: A Case
      Report.
AB  - Avulsion fractures of the tibial tuberosity are uncommon injuries. A 16-year-old
      male sustained injuries to his right knee joint after jumping from stairs and
      landed on his feet with his right knee forced into flexion. X-ray photographs
      showed a type III avulsion fracture of the tibial tuberosity. On the next day of
      the injury, open reduction and internal fixation, followed by arthroscopy was
      performed. The fracture fragment was fixed with three 5.0mm cannulated cancellous
      screws. The torn anterior portion of medial meniscus was repaired with 3-0
      Polydioxanone (PDS) using outside-in sutures and the torn midportion of medial
      meniscus was repaired using the FasT-Fix meniscal repair system. Eight months
      after the injury, removal of the screws and arthroscopy were undertaken. The
      medial meniscus was completely healed. The range of motion was full at the knee
      joint. Meniscal suture should be strongly considered for type III avulsion
      fractures of the tibial tuberosity in adolescents.

PMID- 26306387
TI  - Disclosure, stigma of HIV positive child and access to early infant diagnosis in
      the rural communities of OR Tambo District, South Africa: a qualitative
      exploration of maternal perspective.
AB  - BACKGROUND: Despite the overwhelming evidence confirming the morbidity and
      mortality benefits of early initiation of highly active anti-retroviral therapy
      (HAART) in HIV-infected infants, some children are still disadvantaged from
      gaining access to care. The understanding of the maternal perspective on early
      infant HIV diagnosis and prompt initiation of HAART has not been adequately
      explored, especially in the rural communities of South Africa. This study
      explores the perspectives of mothers of HIV-exposed infants with regard to early
      infant diagnosis (EID) through a lens of social and structural barriers to
      accessing primary healthcare in OR Tambo district, Eastern Cape Province, South
      Africa. METHODS: In this qualitative study, we conducted semi-structured
      interviews at two primary healthcare centres in the King Sabata Dalindyebo
      Municipality of the OR Tambo district, South Africa. Twenty-four purposive sample
      of mothers of HIV-exposed infants took part in the study. Interviews were tape
      recorded, transcribed and field notes were obtained. The findings were
      triangulated with two focus group discussions in order to enrich and validate the
      qualitative data. Thematic content analysis was employed to analyse the data.
      RESULTS: The participants have fairly good knowledge of mother-to-child
      transmission of HIV and the risks during pregnancy, delivery and breastfeeding.
      The majority of participants were confident of the protection offered by anti
      retroviral drugs provided during pregnancy, however, lack knowledge of optimal
      time for early infant diagnosis of HIV. Reasons for not accessing EID included
      fear of finding out that their child is HIV positive, feelings of guilt and/or
      shame and embarrassment with respect to raising an HIV infected infant. Personal
      experiences of HIV diagnosis and HAART were associated with participants'
      attitudes and beliefs toward care-seeking behaviours. Stigma resulting from their
      own disclosure to others reduced their likelihood of recommending EID to other
      members of their communities. CONCLUSION: Despite the good knowledge of mothers
      about infant HIV infection and the availability of treatment, the knowledge of
      the optimal time for early infant diagnosis is lacking. Fear of infant HIV
      diagnosis and stigma are challenges for universal coverage of early infant
      diagnosis in these rural communities. Hence, community education and intensive
      counselling of pregnant women about early infant diagnosis are urgently needed.

PMID- 26306388
TI  - Elimination of motion and pulsation artifacts using BLADE sequences in shoulder
      MR imaging.
AB  - OBJECTIVES: To evaluate the ability of proton-density with fat-suppression BLADE
      (proprietary name for periodically rotated overlapping parallel lines with
      enhanced reconstruction in MR systems from Siemens Healthcare, PDFS BLADE) and
      turbo inversion recovery magnitude-BLADE (TIRM BLADE) sequences to reduce motion
      and pulsation artifacts in shoulder magnetic resonance examinations. MATERIALS
      AND METHODS: Forty-one consecutive patients who had been routinely scanned for
      shoulder examination participated in the study. The following pairs of sequences
      with and without BLADE were compared: (a) Oblique coronal proton-density sequence
      with fat saturation of 25 patients and (b) oblique sagittal T2 TIRM-weighed
      sequence of 20 patients. Qualitative analysis was performed by two experienced
      radiologists. Image motion and pulsation artifacts were also evaluated. RESULTS:
      In oblique coronal PDFS BLADE sequences, motion artifacts have been significantly
      eliminated, even in five cases of non-diagnostic value with conventional imaging.
      Similarly, in oblique sagittal T2 TIRM BLADE sequences, image quality has been
      improved, even in six cases of non-diagnostic value with conventional imaging.
      Furthermore, flow artifacts have been improved in more than 80% of all the cases.
      CONCLUSIONS: The use of BLADE sequences is recommended in shoulder imaging,
      especially in uncooperative patients because it effectively eliminates motion and
      pulsation artifacts.

PMID- 26306389
TI  - Calcific tendinopathy of the rotator cuff: the correlation between pain and
      imaging features in symptomatic and asymptomatic female shoulders.
AB  - OBJECTIVE: To provide new epidemiological data regarding the prevalence,
      distribution and macroscopic features of shoulder rotator cuff calcific
      tendinopathy (calcific tendinopathy), and to identify the characteristics of
      calcific deposits associated with shoulder pain. MATERIALS AND METHODS: Three
      hundred and two female volunteers (604 shoulders) who had been referred to a
      gynaecological clinic participated in the study. The subjects underwent a high
      resolution ultrasonography of both shoulders, and those with a diagnosis of
      calcific tendinopathy compiled a standardized questionnaire relating to shoulder
      symptoms. We determined the prevalence of symptomatic and asymptomatic rotator
      cuff calcific tendinopathy, and compared differences in distribution and
      macroscopic features of the symptomatic and asymptomatic calcifications. RESULTS:
      The prevalence of calcific tendinopathy was 17.8% (103 shoulders). Ninety-five
      shoulders (15.7%) were symptomatic; of these, calcific tendinopathy was found in
      34 shoulders (33%) on imaging. Of the 509 asymptomatic (84.3%) shoulders,
      calcific tendinopathy was observed in 69 cases (67%). Among tendons,
      supraspinatus (53.4%) and infraspinatus (54.6%) were the most frequently
      involved. The majority of calcific deposits were of maximum diameter between 2
      and 5 mm (77.9%), and were linear in form (69.9%). The involvement of multiple
      tendons and a location in the supraspinatus tendon were found to be significantly
      correlated with pain (p = 0.023, p = 0.043 respectively), as were age (p = 0.041)
      and an excessive body mass index (p = 0.024). CONCLUSION: In this sample from the
      general population of working age females, both intrinsic factors (location in
      supraspinatus, multiple tendon involvement) and extrinsic variables (age,
      abnormally high BMI) were correlated with pain in calcific tendinopathy. LEVEL OF
      EVIDENCE: Level III, cross-sectional study, prevalence study.

PMID- 26306390
TI  - Vaccine-induced myositis with intramuscular sterile abscess formation: MRI and
      ultrasound findings.
AB  - Although limb swelling is a well-known complication of vaccination, its rarity
      and wide band of differential diagnosis of limb swelling make it a diagnostic
      challenge. In this case report, we describe three cases of vaccine-induced
      myositis with intramuscular sterile abscess formation in patients with limb
      swelling and their magnetic resonance imaging and ultrasonography findings. Both
      radiologists and clinicians should be familiar with this rare entity, its
      clinical and imaging spectrum, and follow-up strategies. 

PMID- 26306391
TI  - Psychometric properties of the Albanian version of the Orofacial Esthetic Scale:
      OES-ALB.
AB  - The aim was to adapt the Orofacial Esthetic Scale (OES) and to test psychometric
      properties of the Albanian language version in the cultural environment of the
      Republic of Kosovo. METHODS: The OES questionnaire was translated from the
      original English version according to the accepted techniques. The reliability
      (internal consistency), and validity (construct, convergent and discriminative)
      were tested in 169 subjects, test-retest in 61 dental students (DS), and
      responsiveness in 51 prosthodontic patients with treatment needs (PPTN). RESULTS:
      The corrected item correlation coefficients of OES-ALB ranged from 0.686 to
      0.909. The inter-item correlation coefficient ranged between 0.572 and 0.919. The
      Cronbach's alpha was 0.961 and IIC 0.758. Test- retest was confirmed by good ICCs
      and by no significant differences of the OES scores through the period of 14 days
      without any orofacial changes (p > 0.05). Construct validity was proved by the
      presence of one-factor composition that assumed 79.079% of the variance.
      Convergent validity showed significant correlation between one general question
      about satisfaction with orofacial esthetics and the OES summary score, as well as
      between the sum of the 3 OHIP-ALB49 questions related to orofacial aesthetics and
      the OES summary score. Discriminative validity was confirmed with statistically
      significant differences between DS, prosthodontic patients without treatment need
      and PPTN (p < 0.01). Responsiveness was confirmed by a significant increase of
      OES scores after PPTN patients received new fixed partial or removable dentures
      (P < 0.001). CONCLUSION: The results proved excellent psychometric properties of
      the OES-ALB questionnaire in the Republic of Kosovo.

PMID- 26306392
TI  - Structure and function of the healthy pre-adolescent pediatric gut microbiome.
AB  - BACKGROUND: The gut microbiome influences myriad host functions, including
      nutrient acquisition, immune modulation, brain development, and behavior.
      Although human gut microbiota are recognized to change as we age, information
      regarding the structure and function of the gut microbiome during childhood is
      limited. Using 16S rRNA gene and shotgun metagenomic sequencing, we characterized
      the structure, function, and variation of the healthy pediatric gut microbiome in
      a cohort of school-aged, pre-adolescent children (ages 7-12 years). We compared
      the healthy pediatric gut microbiome with that of healthy adults previously
      recruited from the same region (Houston, TX, USA). RESULTS: Although healthy
      children and adults harbored similar numbers of taxa and functional genes, their
      composition and functional potential differed significantly. Children were
      enriched in Bifidobacterium spp., Faecalibacterium spp., and members of the
      Lachnospiraceae, while adults harbored greater abundances of Bacteroides spp.
      From a functional perspective, significant differences were detected with respect
      to the relative abundances of genes involved in vitamin synthesis, amino acid
      degradation, oxidative phosphorylation, and triggering mucosal inflammation.
      Children's gut communities were enriched in functions which may support ongoing
      development, while adult communities were enriched in functions associated with
      inflammation, obesity, and increased risk of adiposity. CONCLUSIONS: Previous
      studies suggest that the human gut microbiome is relatively stable and adult-like
      after the first 1 to 3 years of life. Our results suggest that the healthy
      pediatric gut microbiome harbors compositional and functional qualities that
      differ from those of healthy adults and that the gut microbiome may undergo a
      more prolonged development than previously suspected.

PMID- 26306394
TI  - Patient satisfaction with anaesthesia services and associated factors at the
      University of Gondar Hospital, 2013: a cross-sectional study.
AB  - BACKGROUND: Patient satisfaction is the degree of fulfilling patients'
      anticipation which is an important component and quality indicator in anaesthesia
      service. It can be affected by anaesthetist patient interaction, perioperative
      anaesthetic management and postoperative follow up. No previous study conducted
      in our setup. The aim was to assess patient satisfaction with anaesthesia
      services and associated factors. METHODS: Institutional based cross sectional
      study was conducted from April 15-30, 2013 at the University of Gondar referral
      and teaching hospital. All patients who were operated upon both under general and
      regional anaesthesia during the study period were included. Standardized
      questionnaire used for postoperative patient interview. Data was entered and
      analyzed using Statistical Package for Social Sciences (SPSS) window version 20.
      Chi Square test used to assess the association between each factor and the
      overall satisfaction of patients. The proportion of patients who said they were
      satisfied with anaesthesia services was presented in percentage. RESULTS: A total
      of 200 patients were operated upon under anaesthesia during the study period. Of
      these, a total of 156 patients were included in this study with a response rate
      of 78%. The overall proportion of patients who said they were satisfied with
      anaesthesia services was 90.4%. Factors that affected patient satisfaction
      negatively (dissatisfaction level and p value) were general anaesthesia (12.6%, P
      = 0.046), intraoperative awareness (50%, P = <0.001), pain during operation
      (61.1%, P = <0.001), and pain immediately after operation (25%, P = <0.001)
      respectively. CONCLUSION AND RECOMMENDATION: Patient satisfaction with
      anaesthesia services was low in our setup compared with many previous studies.
      Factors that affected patient satisfaction negatively may be preventable or
      better treated. Awareness creation about the current problem and training need to
      be given for anaesthetists.

PMID- 26306393
TI  - Rifampin use in acute community-acquired meningitis in intensive care units: the
      French retrospective cohort ACAM-ICU study.
AB  - INTRODUCTION: Bacterial meningitis among critically ill adult patients remains
      associated with both high mortality and frequent, persistent disability.
      Vancomycin was added to treatment with a third-generation cephalosporin as
      recommended by French national guidelines. Because animal model studies had
      suggested interest in the use of rifampin for treatment of bacterial meningitis,
      and after the introduction of early corticosteroid therapy (in 2002), there was a
      trend toward increasing rifampin use for intensive care unit (ICU) patients. The
      aim of this article is to report on this practice. METHODS: Five ICUs
      participated in the study. Baseline characteristics and treatment data were
      retrospectively collected from charts of patients admitted with a diagnosis of
      acute bacterial meningitis during a 5-year period (2004-2008). The ICU mortality
      was the main outcome measure; Glasgow Outcome Scale and 3-month mortality were
      also assessed. RESULTS: One hundred fifty-seven patients were included.
      Streptococcus pneumoniae and Neisseria meningitidis were the most prevalent
      causative microorganisms. The ICU mortality rate was 15%. High doses of a
      cephalosporin were the most prevalent initial antimicrobial treatment. The delay
      between admission and administration of the first antibiotic dose was correlated
      with ICU mortality. Rifampin was used with a cephalosporin for 32 patients
      (ranging from 8% of the cohort for 2004 to 30% in 2008). Administration of
      rifampin within the first 24 h of hospitalization could be associated with a
      lower ICU survival. Statistical association between such an early rifampin
      treatment and ICU mortality reached significance only for patients with
      pneumococcal meningitis (p=0.031) in univariate analysis, but not in the logistic
      model. CONCLUSIONS: We report on the role of rifampin use for patients with
      community-acquired meningitis, and the results of this study suggest that this
      practice may be associated with lower mortality in the ICU. Nevertheless, the
      only independent predictors of ICU mortality were organ failure and pneumococcal
      infection. Further studies are required to confirm these results and to explain
      how rifampin use would reduce mortality.

PMID- 26306395
TI  - Anti-malarial prescription practices among children admitted to six public
      hospitals in Uganda from 2011 to 2013.
AB  - BACKGROUND: In 2011, Uganda's Ministry of Health switched policy from presumptive
      treatment of malaria to recommending parasitological diagnosis prior to
      treatment, resulting in an expansion of diagnostic services at all levels of
      public health facilities including hospitals. Despite this change, anti-malarial
      drugs are often prescribed even when test results are negative. Presented is data
      on anti-malarial prescription practices among hospitalized children who underwent
      diagnostic testing after adoption of new treatment guidelines. METHODS: Anti
      malarial prescription practices were collected as part of an inpatient malaria
      surveillance program generating high quality data among children admitted for any
      reason at government hospitals in six districts. A standardized medical record
      form was used to collect detailed patient information including presenting
      symptoms and signs, laboratory test results, admission and final diagnoses,
      treatments administered, and final outcome upon discharge. RESULTS: Between July
      2011 and December 2013, 58,095 children were admitted to the six hospitals
      (hospital range 3294-20,426).A total of 56,282 (96.9 %) patients were tested for
      malaria, of which 26,072 (46.3 %) tested positive (hospital range 5.9-57.3 %).
      Among those testing positive, only 84 (0.3 %) were first tested after admission
      and 295 of 30,389 (1.0 %) patients who tested negative at admission later tested
      positive. Of 30,210 children with only negative test results, 11,977 (39.6 %)
      were prescribed an anti-malarial (hospital range 14.5-53.6 %). The proportion of
      children with a negative test result who were prescribed an anti-malarial
      fluctuated over time and did not show a significant trend at any site with the
      exception of one hospital where a steady decline was observed. Among those with
      only negative test results, children 6-12 months of age (aOR 3.78; p < 0.001) and
      those greater than 12 months of age (aOR 4.89; p < 0.001) were more likely to be
      prescribed an anti-malarial compared to children less than 6 months of age.
      Children with findings suggestive of severe malaria were also more likely to be
      prescribed an anti-malarial after a negative test result (aOR 1.98; p < 0.001).
      CONCLUSIONS: Despite high testing rates for malaria at all sites, prescription of
      anti-malarials to patients with negative test results remained high, with the
      exception of one site where a steady decline occurred.

PMID- 26306396
TI  - Combining microscopy with mesoscopy using optical and optoacoustic label-free
      modes.
AB  - Biology requires observations at multiple geometrical scales, a feature that is
      not typically offered by a single imaging modality. We developed a hybrid optical
      system that not only provides different contrast modes but also offers imaging at
      different geometrical scales, achieving uniquely broad resolution and a 1000-fold
      volume sampling increase compared to volumes scanned by optical microscopy. The
      system combines optoacoustic mesoscopy, optoacoustic microscopy and two-photon
      microscopy, the latter integrating second and third harmonic generation modes.
      Label-free imaging of a mouse ear and zebrafish larva ex-vivo demonstrates the
      contrast and scale complementarity provided by the hybrid system. We showcase the
      superior anatomical orientation offered by the label-free capacity and hybrid
      operation, over fluorescence microscopy, and the dynamic selection between field
      of view and resolution achieved, leading to new possibilities in biological
      visualization. 

PMID- 26306397
TI  - Jugular venipuncture and other innovative approaches to phlebotomy among people
      who inject drugs.
AB  - In their recent paper on patient experiences of accessing phlebotomy services in
      hospital outpatient clinics, Clements and colleagues state that there is a real
      need to better understand the responses of people who inject drugs to phlebotomy.
      They discuss the reasons why people who inject drugs might not be accessing
      healthcare services, especially in relation to treatment for hepatitis C. Their
      research is a welcome addition to the literature that emphasizes the stigma and
      discrimination faced by people who inject drugs, including within healthcare
      settings, and outlines the need to promote effective partnerships between
      healthcare workers and patients so as to deliver the best health outcomes. 

PMID- 26306398
TI  - Stable genetic diversity despite parasite and pathogen spread in honey bee
      colonies.
AB  - In the last decades, the rapid spread of diseases, such as varroosis and
      nosemosis, associated with massive honey bee colonies mortality around the world
      has significantly decreased the number and size of honey bee populations and
      possibly their genetic diversity. Here, we compare the genetic diversity of
      Iberian honey bee colonies in two samplings performed in 2006 and 2010 in
      relation to the presence of the pathogenic agents Nosema apis, Nosema ceranae,
      and Varroa destructor in order to determine whether parasite and pathogen spread
      in honey bee colonies reflects changes in genetic diversity. We found that the
      genetic diversity remained similar, while the incidence of N. ceranae increased
      and the incidence of N. apis and V. destructor decreased slightly. These results
      indicate that the genetic diversity was not affected by the presence of these
      pathogenic agents in the analyzed period. However, the two groups of colonies
      with and without Nosema/Varroa detected showed significant genetic
      differentiation (G test). A detailed analysis of the allelic segregation of
      microsatellite loci in Nosema/Varroa-negative colonies and parasitized ones
      revealed two outlier loci related to genes involved in immune response.

PMID- 26306399
TI  - Cardiovascular disease in Europe--epidemiological update 2015.
AB  - This article provides an update for 2015 on the burden of cardiovascular disease
      (CVD), with a particular focus on coronary heart disease (CHD) and stroke, across
      the countries of Europe. Cardiovascular disease is still the most common cause of
      death within Europe, causing almost two times as many deaths as cancer across the
      continent. Although there is clear evidence, where data are available, that
      mortality from CHD and stroke has decreased substantially over the last 5-10
      years, there are still large inequalities found between European countries, in
      both current rates of death and the rate at which these decreases have occurred.
      Similarly, rates of treatment, particularly surgical intervention, differ widely
      between those countries for which data are available, indicating a range of
      inequalities between them. This is also the first time in the series that we use
      the 2013 European Standard Population (ESP) to calculate age-standardized death
      rates (ASDRs). This new standard results in ASDRs around two times as large as
      the 1976 ESP for CVD conditions such as CHD but changes little the relative
      rankings of countries according to ASDR.

PMID- 26306401
TI  - Assessment of Aprotinin Loaded Microemulsion Formulations for Parenteral Drug
      Delivery: Preparation, Characterization, in vitro Release and Cytotoxicity
      Studies.
AB  - The object of the current study was to prepare novel microemulsion formulations
      of aprotinin for parenteral delivery and to compare in vitro characteristics and
      release behaviour of different Technetium-99m ((99m)Tc)-Aprotinin loaded
      microemulsion formulations. In addition, cytotoxicity of microemulsion
      formulation was evaluated with cell culture studies on human immortalized
      pancreatic duct epithelial-like cells. For this aim, firstly, pseudo-ternary
      phase diagrams were plotted to detect the formulation region and optimal
      microemulsions were characterized for their thermodynamic stability,
      conductivity, particle size, zeta potential, viscosity, pH and in vitro release
      properties. For in vitro release studies aprotinin was labelled with (99m)Tc and
      labelling efficiency, radiochemical purity and stability of the radiolabeled
      complex were determined by several chromatography techniques. Radiolabeling
      efficiency of (99m)Tc-Aprotinin was found over than 90% without any significant
      changes up to 6 hours after labelling at room temperature. After that, in vitro
      release studies of (99m)Tc-Aprotinin loaded microemulsions were performed with
      two different methods; dissolution from diffusion cells and dialysis bags. Both
      methods showed that release rate of (99m)Tc- Aprotinin from microemulsion could
      be controlled by microemulsion formulations. Drug release from the optimized
      microemulsion formulations was found lower compared to drug solution at the end
      of six hours. According to stability studies, the optimized formulation was found
      to be stable over a period of 12 months. Also, human immortalized pancreatic duct
      epithelial-like cells were used to evaluate the cytotoxicity of optimum
      formulation. Developed microemulsion did not reveal cytotoxicity. In conclusion
      the present study indicated that the M1-APT microemulsion is appropriate for
      intravenous application of aprotinin. 

PMID- 26306400
TI  - Effects of hexanic extract of Serenoa repens (Permixon(r) 160 mg) on inflammation
      biomarkers in the treatment of lower urinary tract symptoms related to benign
      prostatic hyperplasia.
AB  - BACKGROUND: Chronic prostatic inflammation (CPI) could be a cause of symptomatic
      or complicated benign prostatic hyperplasia (BPH). In previous in vitro and in
      vivo studies, Hexanic Extract of Serenoa repens (HESr) namely Permixon((r)) has
      demonstrated potent anti-inflammatory properties. With the aim to provide new
      insight onto HESr anti-inflammatory properties in human we explore its effect on
      CPI biomarkers in men with lower urinary tract symptoms (LUTS) related to BPH
      using a non-invasive method and investigate links between biomarkers and clinical
      symptoms. METHODS: An international, randomized, double-blind, parallel-group,
      tamsulosin-controlled study was carried out in 206 men with BPH-related LUTS.
      Patients received oral daily HESr 320mg or tamsulosin 0.4 mg during 3 months. The
      first urine stream after digital rectal examination (DRE) was collected at Day 1
      and Day 90 and mRNA was extracted from prostatic epithelial cells desquaming in
      the lumen of the glands and seminal plasma fluid after DRE. mRNA quantification
      of the 29 most significant published inflammation markers in BPH and protein
      detection in urine was performed. RESULTS: At D90, a decrease in mean gene
      expression was observed for 65.4% of the markers detected in the HESr group
      versus 46.2% in the tamsulosin group. In the 15 most frequently expressed genes,
      this difference was higher (80% vs. 33% respectively). Three proteins (MCP
      1/CCL2, IP-10/CXCL10, and MIF) were detected. At D90, a decrease in the number of
      patients who expressed MCP-1/CCL2 and IP-10/CXCL10 was observed only in the HESr
      group. Moreover, MIF expression was significantly reduced by HESr compared with
      tamsulosin (P = 0.007). Finally, in contrast to tamsulosin, the subgroup of
      patients treated by HESr and who over expressed MIF at baseline, had a higher
      response to the International Prostate Symptom Score (I-PSS) than those who did
      not over express this protein (mean I-PSS change: -6.4 vs. -4.5 respectively). As
      the study is exploratory, results should be confirmed in a powered clinical
      study. CONCLUSIONS: These results showed for the first time at clinical level the
      anti-inflammatory properties of HESr, already indicated in BPH-related LUTS.
      Thus, HESr could be of interest to prevent unfavourable evolution in patients
      with CPI.

PMID- 26306402
TI  - MiR-100 Inhibits Osteosarcoma Cell Proliferation, Migration, and Invasion and
      Enhances Chemosensitivity by Targeting IGFIR.
AB  - MicroRNAs are highly conserved noncoding RNA that negatively modulate protein
      expression at a posttranscriptional and/or translational level. MicroRNAs play an
      important role in the development and progression of human cancers, including
      osteosarcoma. Recent studies have shown that miR-100 was downregulated in many
      cancers; however, the role of miR-100 in human osteosarcoma has not been totally
      elucidated. In this study, we demonstrate that the expression of miR-100 was
      significantly downregulated in human osteosarcoma tissues compared to the
      adjacent tissues. Enforced expression of miR-100 inhibited cell proliferation,
      migration, and invasion abilities of osteosarcoma cells, U-2OS, and MG-63.
      Additionally, miR-100 also sensitized osteosarcoma cells to cisplatin and
      promoted apoptosis. Furthermore, overexpression of miR-100 decreased the
      expression of insulin-like growth factor I receptor and inhibited PI3K/AKT and
      MAPK/ERK signaling. In human clinical specimens, insulin-like growth factor I
      receptor was inversely correlated with miR-100 in osteosarcoma tissues.
      Collectively, our results demonstrate that miR-100 is a tumor suppressor microRNA
      and indicate its potential application for the treatment of osteosarcoma in
      future.

PMID- 26306403
TI  - Multi-modal CT in acute stroke: wait for a serum creatinine before giving
      intravenous contrast? No!
AB  - BACKGROUND: Multi-modal CT (MMCT) to guide decision making for reperfusion
      treatment is increasingly used, but there remains a perceived risk of contrast
      induced nephropathy (CIN). At our center, MMCT is used empirically without
      waiting for serum-creatinine (sCR) or renal profiling. AIMS: To determine the
      incidence of CIN, examine the risk factors predisposing to its development, and
      investigate its effects on clinical outcome in the acute stroke population.
      METHODS: An institution-wide protocol was implemented for acute stroke
      presentations to have MMCT (100-150 ml nonionic tri-iodinated contrast, perfusion
      CT and CT angiography) without waiting for serum-creatinine to minimize delays.
      Intravenous saline is routinely infused (80-125 ml/h) for at least 24-h after
      MMCT. Serial creatinine levels were measured at baseline, risk period, and follow
      up. Renal profiles and clinical progress were reviewed up to 90 days. RESULTS: We
      analyzed 735 consecutive patients who had MMCT for the evaluation of acute
      ischemic or hemorrhagic stroke during the last five-years. A total of 623
      patients met the inclusion criteria for analysis: 16 cases (2.6%) biochemically
      qualified as CIN; however, the risk period serum-creatinine for 15 of these cases
      was confounded by dehydration, urinary tract infection, or medications. None of
      the group had progression to chronic kidney disease or required dialysis.
      CONCLUSIONS: The incidence of CIN is low when MMCT is used routinely to assess
      acute stroke patients. In this population, CIN was a biochemical phenomenon that
      did not have clinical manifestations, cause chronic kidney disease, require
      dialysis, or negatively impact on 90-day mRS outcomes. Renal profiling and
      waiting for a baseline serum-creatinine are an unnecessary delay to emergency
      reperfusion treatment.

PMID- 26306404
TI  - Relationship between fracture-relevant parameters of thoracolumbar burst
      fractures and the reduction of intra-canal fracture fragment.
AB  - OBJECTIVE: Posterior longitudinal ligament reduction (PLLR) has been widely used
      for treatment of thoracolumbar burst fractures. However, there are no systemic
      studies assessing the influence of position parameters of intra-canal fracture
      fragment (IFF) itself on outcome of reduction. The aim of this study was to
      analyze the relationship between position parameters of IFF and the reduction
      efficacy of PLLR. METHODS: Sixty-two patients (average age, 36.9 years) with
      single thoracolumbar burst fractures and intact posterior longitudinal ligaments
      were recruited. Patients were divided into reduced and unreduced groups based on
      IFF reduction situations by PLLR. Preoperative and intraoperative computed
      tomography (CT) were used to evaluate reduction and location parameters of IFF,
      such as position, width, height, inversion, and horizontal angle, ratio of width
      of IFF to the transverse diameter of vertebral canal (R 1), and ratio of height
      of IFF to height of injured vertebrae (R 2) before and after PLLR. RESULTS: There
      were significant differences in width (P < 0.001), height (P = 0.0141; R 1, P <
      0.001), and R 2 (P = 0.0045) between the two groups. When width of IFF was more
      than 75 % of transverse diameter of vertebral canal and height of IFF was more
      than 47 % of height of injured vertebrae, the IFF could not be reduced by PLLR.
      CONCLUSIONS: In patients with thoracolumbar burst fractures, IFF in apterium of
      the posterior longitudinal ligament cannot be reduced by PLLR. For thoracolumbar
      burst fractures that cover the posterior longitudinal ligament, the width and
      height of IFF are important parameters that influence reduction quality.

PMID- 26306405
TI  - Orthostatic Hypotension and Risk of Venous Thromboembolism in 2 Cohort Studies.
AB  - BACKGROUND: Although venous stasis is a risk factor for venous thromboembolism
      (VTE) and orthostatic hypotension (OH) can cause venous stasis, to our knowledge
      no study has examined the relationship between OH and VTE risk. We sought to
      quantify the association between OH and VTE (deep vein thrombosis or pulmonary
      embolism) using data from 2 large, prospective cohort studies: the Cardiovascular
      Health Study (CHS) and the Atherosclerosis Risk in Communities (ARIC) Study. We
      hypothesized that OH was positively associated with incident VTE. METHODS: We
      measured OH-defined as a drop in systolic blood pressure (SBP) of at least 20 mm
      Hg or diastolic blood pressure (DBP) of at least 10 mm Hg within 3 minutes of
      standing-in participants aged 45-64 years in ARIC (n = 12,480) and >=65 years in
      CHS (n = 5,027) at baseline visits (1987-1989 in ARIC; 1989-1990 and 1992-1993 in
      CHS), and followed participants for incident VTE (n = 568 in ARIC through 2011
      and n = 148 in CHS through 2001). We calculated adjusted hazard ratios (HRs) and
      their 95% confidence intervals (CIs) for incident VTE in relation to OH status.
      RESULTS: In CHS, there was a positive association between OH status and incident
      VTE (HR for VTE = 1.74 (95% CI: 1.20-2.51)). In contrast, there was no
      association between OH and VTE in the ARIC study (HR for VTE = 0.97 (95% CI: 0.70
      1.33)). CONCLUSIONS: Community-dwelling older adults with OH had a moderately
      increased risk of VTE. These results were not seen in a population-based middle
      aged cohort.

PMID- 26306406
TI  - Evaluation of the efficacy of systemic miltefosine associated with photodynamic
      therapy with liposomal chloroaluminium phthalocyanine in the treatment of
      cutaneous leishmaniasis caused by Leishmania (L.) amazonensis in C57BL/6 mice.
AB  - BACKGROUND: The shortage of drugs is a concern and has become the object of
      studies to discover effective alternatives for cutaneous leishmaniasis (CL)
      treatment. A topical formulation has been sought due to its low toxicity.
      Development of alternative therapies, such as multimodal ones, is important in
      confronting drug resistance. This study aims to compare the in vivo efficacy of
      topical photodynamic therapy (PDT) using liposomal chloroaluminium phthalocyanine
      (AlClPC) in the treatment of CL, isolated and associated with systemic therapy
      with miltefosine. METHODS: Five groups were adopted, each one with six isogenic
      adult female mice C57BL/6: (1) Negative Control-non-infected and non-treated; (2)
      Positive Control (PBS)-infected and non-treated; (3) Miltefosine-infected and
      treated with oral miltefosine 200 mg/kg/day; (4) Infected and treated with PDT
      with topical AlClPC (500 MUL) on alternate days; (5) Oral Miltefosine 200
      mg/kg/day and PDT with topical AlClPC (500 MUL) on alternate days. Therapeutic
      schemes lasted 20 days. Infection was confirmed by culture in Nove-McNeal-Nicolle
      medium (NNN) of lymph collected from the animal paw, and animals were evaluated
      by paw measurement and parasitological criteria. RESULTS: Miltefosine associated
      with PDT with AlClPC promoted a significant reduction in parasite number and
      viability when compared to the other infected groups, also returning the paw
      diameter to a size similar to the negative control group after 20 days of
      treatment. CONCLUSIONS: Association of miltefosine with PDT mediated by topical
      AlClPC represents hopes for CL treatment, an increasing dermatological disease in
      some countries.

PMID- 26306408
TI  - Assessing the Relationship between Semantic Processing and Thought Disorder
      Symptoms in Schizophrenia.
AB  - Aberrant semantic processing has been linked to the etiology of formal thought
      disorder (TD) symptoms in schizophrenia. In this cross-sectional study, two
      prominent theories, overactivation and disorganized structure of semantic memory
      (SM), were examined in relation to TD symptoms using the continuum approach
      across two established semantic tasks (direct/indirect semantic priming and
      categorical fluency). The aim was to examine the validity of the two TD theories
      in relation to TD symptoms in schizophrenia. Greater direct and indirect priming,
      fluency productivity and category errors were expected if the data supported the
      overactivation theory. Reduced fluency productivity and increased category errors
      would be characteristic of disorganized storage. Fifty-seven
      schizophrenia/schizoaffective disorder patients and 48 controls completed a
      clinical assessment and the semantic tasks. There was significantly reduced
      direct priming in patients compared to controls (p<.05), while indirect priming
      was not significantly different; there was no association between TD and degree
      of priming. Patients produced more category-inappropriate words (p<.005) than
      controls, which was related to increasing severity of circumstantiality. The
      pattern of results was more indicative of a disorganized SM storage problem in
      this sample. This phenomenon may underlie some TD symptoms in general
      schizophrenia. The findings strengthen the relationship between SM deficits and
      TD symptoms, though this appears to differ between individual symptoms. The
      authors discuss the value of the continuum approach in addressing research
      questions in TD etiology. Given low levels of TD in this study, replication of
      these findings in a sample with greater TD is desirable.

PMID- 26306407
TI  - Heterogeneous natural selection on oxidative phosphorylation genes among fishes
      with extreme high and low aerobic performance.
AB  - BACKGROUND: Oxidative phosphorylation (OXPHOS) is the primary source of ATP in
      eukaryotes and serves as a mechanistic link between variation in genotypes and
      energetic phenotypes. While several physiological and anatomical factors may lead
      to increased aerobic capacity, variation in OXPHOS proteins may influence OXPHOS
      efficiency and facilitate adaptation in organisms with varied energy demands.
      Although there is evidence that natural selection acts on OXPHOS genes, the focus
      has been on detection of directional (positive) selection on specific
      phylogenetic branches where traits that increase energetic demands appear to have
      evolved. We examined patterns of selection in a broader evolutionary context,
      i.e., on multiple lineages of fishes with extreme high and low aerobic
      performance. RESULTS: We found that patterns of natural selection on
      mitochondrial OXPHOS genes are complex among fishes with different swimming
      performance. Positive selection is not consistently associated with high
      performance taxa and appears to be strongest on lineages containing low
      performance taxa. In contrast, within high performance lineages, purifying
      (negative) selection appears to predominate. CONCLUSIONS: We provide evidence
      that selection on OXPHOS varies in both form and intensity within and among
      lineages through evolutionary time. These results provide evidence for
      fluctuating selection on OXPHOS associated with divergence in aerobic
      performance. However, in contrast to previous studies, positive selection was
      strongest on low performance taxa suggesting that adaptation of OXPHOS involves
      many factors beyond enhancing ATP production in high performance taxa. The
      broader pattern indicates a complex interplay between organismal adaptations, ATP
      demand, and OXPHOS function.

PMID- 26306409
TI  - Microbiological characterization of Salmonella enterica serotype Paratyphi, South
      Africa, 2003-2014.

PMID- 26306410
TI  - Fish collagen/alginate/chitooligosaccharides integrated scaffold for skin tissue
      regeneration application.
AB  - An emerging paradigm in wound healing techniques is that a tissue-engineered skin
      substitute offers an alternative approach to create functional skin tissue. Here
      we developed a fish collagen/alginate (FCA) sponge scaffold that was
      functionalized by different molecular weights of chitooligosaccharides (COSs)
      with the use of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride as a
      cross-linking agent. The effects of cross-linking were analyzed by Fourier
      transform infrared spectroscopy. The results indicate that the homogeneous
      materials blending and cross-linking intensity were dependent on the molecular
      weights of COSs. The highly interconnected porous architecture with 160-260MUm
      pore size and over 90% porosity and COS's MW driven swelling and retention
      capacity, tensile property and in vitro biodegradation behavior guaranteed the
      FCA/COS scaffolds for skin tissue engineering application. Further improvement of
      these properties enhanced the cytocompatibility of all the scaffolds, especially
      the scaffolds containing COSs with MW in the range of 1-3kDa (FCA/COS1) showed
      the best cytocompatibility. These physicochemical, mechanical, and biological
      properties suggest that the FCA/COS1 scaffold is a superior candidate that can be
      used for skin tissue regeneration. 

PMID- 26306411
TI  - Antioxidant, antibacterial and in vivo dermal wound healing effects of Opuntia
      flower extracts.
AB  - Opuntia ficus-indica flowers are used for various medicinal purposes. The aims of
      the present investigation were to evaluate biological properties of O. ficus
      indica flowers extracts and to investigate its antioxidant and antibacterial
      activities and its ability to enhance wound healing. The wound healing activity
      of the mucilaginous and methanol extracts of O. ficus-indica flowers were
      assessed using excision wound model in rats. After thirteen days of treatment by
      both extracts, a beneficial effect on cutaneous repair was observed as assessed
      by the acceleration of wound contraction and remodeling phases. Histopathological
      studies of the granulation tissue indicated that the derma is properly arranged
      with the Opuntia flowers extract, compared with the control group. The mucilage
      extract was more effective than the methanol extract, but both showed significant
      results compared with the control. Such investigation was supported by the
      efficiency of the methanolic and mucilage extract as antimicrobial and
      antioxidant. Indeed, the extracts showed a potential antioxidant activity
      determined by different test systems, namely DPPH radicals scavenging activity,
      trolox equivalent antioxidant capacity, reducing power, beta-carotene bleaching
      assay and metal chelating activity and exhibited significant antibacterial
      activity against almost all tested bacteria. 

PMID- 26306412
TI  - Molecular bioimprinting of lipases with surfactants and its functional
      consequences in low water media.
AB  - Lipases from Thermomyces lanuginosa (TLL), Candida rugosa (CRL) and Burkholderia
      cepacia (BCL) were obtained in the 'open lid' form by adding surfactant molecules
      like n-octyl-beta-d-glucopyranoside (OG), hexadecyl trimethyl ammonium bromide
      (CTAB), Bis(2-ethylhexyl) sulfosuccinate sodium salt (AOT) and triton X-100 for
      this purpose. The enzymes were 'dried' by precipitating with 4* (v/v) excess of
      organic solvents. The imprint surfactant molecules were removed by extensive
      washing with organic solvents. TLL imprinted with 0.05% CTAB showed 11-fold
      increase in the transesterification activity and was a better preparation to
      kinetically resolve (+/-)-1-phenylethanol. Fluorescence emission spectra
      confirmed that Trp89 of the lid was indeed affected during bioimprinting. With
      CRL, bioimprinting with OG gave 7-fold increase in the transesterification rates
      and resulted in reversal of enantioselectivity of CRL and gave R-phenylethyl
      acetate instead of the S-product as with the unimprinted precipitate.
      Bioimprinted BCL was also a 7-fold better catalyst for transesterification as
      well as enantioselectivity. 

PMID- 26306413
TI  - Isolation and characterization of curdlan produced by Agrobacterium HX1126 using
      alpha-lactose as substrate.
AB  - A strain Agrobacterium HX1126 was isolated from soil sample near the canal in
      Wuxi. alpha-lactose was used as the sole carbon source for the production of an
      exopolysaccharide which was named PLHX. The highest production of PLHX (21.4g/L)
      was obtained under nitrogen depletion. PLHX composed mainly of glucose, with
      lower amounts of galactose and aminogalactose. The structure of the product was
      confirmed by NMR and FTIR and was identified as curdlan. This exopolysaccharide
      formed a gel when 30g/L was put in boiling water for 10min, with an achieved gel
      strength of 831g/cm(2). Moreover, a hypothesis for higher gel strength production
      is proposed. The gel forming property makes this exopolysaccaride a good
      potential application in the food, pharmaceutical and cosmetic industries. 

PMID- 26306414
TI  - Preparation and characterization of Lignin-graft-poly (E-caprolactone) copolymers
      based on lignocellulosic butanol residue.
AB  - In this paper, a "graft from" Ring-Opening Polymerization (ROP) technique was
      used to synthesize a lignin-graft-poly (E-caprolactone) copolymer (BBL-g-PCL)
      using biobutanol lignin (BBL) as raw material recovered from lignocellulosic
      butanol residue. Polymerizations were carried out with various mass ratios of BBL
      and CL monomer ([BBL]/([BBL]+[CL])=1.0%, 5.0%, 10%, 20% and 40% (w/w)) to obtain
      BBL-g-PCL copolymers with different molecular weights, ranging from 367 to
      8163gmol(-1). The grafting efficiency was preliminary evidenced by the long-term
      stability of dissolution of BBL-g-PCL in toluene. FT-IR and NMR analysis provided
      the further evidences for successful formation of BBL-g-PCL copolymer. The
      thermal properties of BBL-g-PCL copolymers were characterized by differential
      scanning calorimetry (DSC) and thermogravimetric analysis (TGA). These results
      indicated that BBL-g-PCL copolymer had relatively good thermal stability. The
      static contact angle of BBL-g-PCL coating film reached to 80 degrees . The
      surface functional groups and chemical composition of BBL-g-PCL copolymer was
      investigated in detail by X-ray photoelectron spectroscopy (XPS). The surface
      morphology of BBL-g-PCL copolymer was studied by Atomic force microscopy (AFM).
      Additionally, BBL-g-PCL coating film exhibited high absorption in the ultraviolet
      (UV) range, which could allow for applications in UV-blocking coatings, as well
      as the extents for the utilization of lignocellulosic butanol residue. 

PMID- 26306415
TI  - Challenges to the management of curable sexually transmitted infections.
AB  - Each year, hundreds of millions of new cases of curable sexually transmitted
      infections (STIs) occur worldwide resulting in reproductive and other serious
      sequelae, as well as enhanced transmission of HIV. The clinical management and
      control of these STIs should include as a minimum access to services that provide
      timely and accurate diagnostic testing together with effective treatment. The
      provision of appropriate treatment is challenged by the development of increasing
      antimicrobial resistance, in particular with gonorrhoea and Mycoplasma genitalium
      infections, requiring new treatments and management algorithms. In addition,
      infections such as chlamydia, syphilis and trichomoniasis, which show few signs
      of resistance, are nevertheless highly prevalent and require better public health
      control measures. While these may be achievable in high income countries, they
      are still beyond the reach of many low and middle income countries, making
      substantial improvements in STI management and reductions in STI prevalence
      challenging. 

PMID- 26306416
TI  - Association of serum zinc levels with liver function and survival in patients
      awaiting liver transplantation.
AB  - PURPOSE: Zinc is an important trace element with catalytic and defensive
      functions. We assessed the impact of zinc deficiency in patients with end-stage
      liver disease awaiting liver transplantation. METHODS: Serum zinc levels were
      measured at the time of evaluation for liver transplantation (n = 368). Patients
      were dichotomized in two groups based on low and normal zinc serum levels.
      RESULTS: Serum zinc levels are tightly associated with liver function as patients
      with low zinc levels (n = 226) had a higher Model for End-Stage Liver Disease
      (MELD) score (15.0 [5.0-40.0]) than patients with normal zinc (n = 142) levels
      (9.0 [6.0-34.0]; p < 0.00). Multivariate analysis demonstrated that serum zinc
      levels function as an independent predictor of hepatic decompensation (hydropic
      decompensation: odds ratio [OR] 0.82; 95% confidence interval [CI] 0.70-0.96; p =
      0.015; hepatic encephalopathy: OR 0.80; 95% CI 0.71-0.90; p = 0.000; spontaneous
      bacterial peritonitis: OR 0.85; 95% CI 0.72-1.00; p = 0.047; hepatorenal
      syndrome: OR 0.83; 95% CI 0.72-0.95; p = 0.011). Actuarial survival free of liver
      transplantation was reduced for low-zinc patients (26.7 +/- 4.0 months; 95% CI
      18.8-34.6) compared to patients with normal zinc levels (30.9 +/- 3.0 months; 95%
      CI 24.9-36.9; p = 0.008). Reduction of zinc levels for patients on the
      transplantation list resulted in a 28.3-fold increased risk of death/liver
      transplantation (95% CI 3.2-244.8, p < 0.001). CONCLUSIONS: Serum zinc levels are
      associated with reduced survival in end-stage liver disease patients. Whether or
      not zinc supplementation might be beneficial for patients on a liver
      transplantation list requires further study.

PMID- 26306417
TI  - Therapeutic and immunoregulatory effect of GATA-binding protein-3/T-box expressed
      in T-cells ratio of astragalus polysaccharides on 2,4,6-trinitrobenzene sulfonic
      acid-induced colitis in rats.
AB  - OBJECTIVE: To analyze the immunological characteristics of 2,4,6-trinitrobenzene
      sulfonic acid (TNBS)-induced colitis model and examine the therapeutic effects
      and mechanisms of Astragalus polysaccharides (APS) treatment. METHODS: Thirty-two
      male specific pathogen free Spragne-Dawley rats were randomly equally assigned to
      four groups: control, TNBS, APS and prednisone groups. Experimental colitis was
      induced by enema administration of TNBS. Then rats were treated with APS (0.5
      g*kg-1*day-1, once daily) or prednisone (1.0 mg*kg-1*day-1, once daily) by gavage
      for 14 days. Macroscopic lesion and histological damage were determined, and
      activity of myeloperoxidase (MPO) was measured in the colonic tissues.
      Expressions of T-box expressed in T-cells (T-bet) and GATA-binding protein-3
      (GATA-3) were determined by immunohistochemistry analysis and western blot.
      RESULTS: Both macroscopic lesion and histological colonic damage induced by TNBS
      were reduced by APS and prednisone treatment. These were accompanied by
      significant attenuation of MPO activity (P=0.03). TNBS intervention enhanced the
      expression of both GATA-3 and T-bet, but the expression of T-bet was
      significantly enhanced than that of GATA-3, resulting in significant reduction of
      GATA-3/T-bet ratio (P=0.025). APS administration enhanced the expression of T-bet
      (P=0.04) and GATA-3 (P=0.019) in comparison to TNBS group, and resulting in an up
      regulated GATA-3/T-bet ratio. Prednisone treatment inhibited both expressions;
      however it also resulted in up-regulation of the GATA-3/T-bet ratio. CONCLUSIONS:
      These results demonstrated that APS exerted a beneficial immune regulatory effect
      on experimental colitis. It promoted the expression of T helper cell 1 (Th1) and
      T helper cell 2 (Th2) specific transcription factors but ultimately favor a shift
      toward Th2 phenotype, suggesting that APS possessed therapeutic potential in
      experimental colitis.

PMID- 26306418
TI  - Dispensing good sleep health behaviours not pills--a cluster-randomized
      controlled trial to test the feasibility and efficacy of pharmacist-provided
      brief behavioural treatment for insomnia.
AB  - Behavioural therapies are recommended as the first-line treatment of insomnia;
      however, sedatives and hypnotics constitute the main treatment modality used in
      primary care. Community pharmacies provide a unique conduit for identifying and
      providing appropriate treatment for those with insomnia either purchasing
      prescription sedatives or seeking over-the-counter treatments. A feasibility
      study using a cluster-randomized controlled trial, testing the efficacy of
      trained pharmacists providing behavioural interventions such as stimulus control
      and sleep restriction to patients with insomnia, in improving insomnia severity
      was conducted. The intervention involved three pharmacy visits (baseline, 1 and 3
      months follow-up). The control group received usual care and information sheets
      on insomnia. The primary outcome was the Insomnia Severity Index. Twelve
      community pharmacists (five control, seven intervention) in New South Wales,
      Australia were recruited and trained. These pharmacists, in turn, recruited 46
      patients (22 control, 24 intervention (mean age 53.7 +/- 18.4, 72% females) and
      delivered a brief behavioural therapy intervention. The overall decrease in
      Insomnia Severity Index from baseline to the 3-month follow-up in the
      intervention group, n = 17 (7.6 +/- 4.3 points), was significantly greater than
      for the control group, n = 19 (2.9 +/- 8.8 points) (mean difference 4.6, 95%
      confidence interval: 0.005-9.2, P = 0.05). However, when the effect of clustering
      was taken into account using a mixed-effects model, the estimated difference in
      Insomnia Severity Index (change from baseline to visit 3) between the
      intervention and control groups was not significant (group difference in Insomnia
      Severity Index change = 3.78, 95% confidence interval: -0.81 to 8.37, P = 0.11;
      intracluster correlation = 0.18). The study highlights the use of a novel venue
      to deliver brief behavioural therapies for insomnia using trained non
      psychologist health professionals. Although, when cluster effect was taken into
      account, the difference in Insomnia Severity Index reduction between the
      intervention versus control groups was non-significant, the results highlight
      that reductions in insomnia severity can be gained using trained pharmacists
      providing brief behavioural interventions. Future research in this area is
      warranted, with appropriately sized studies using the conventional, robust
      randomized trial design.

PMID- 26306419
TI  - The effect of forceps manipulation for expert pediatric surgeons using an
      endoscopic pseudo-viewpoint alternating system: the phenomenon of economical slow
      and fast performance in endoscopic surgery.
AB  - PURPOSE: Endoscopic surgery is performed under a horizontal view in comparison to
      the vertical view that is associated with open surgery. We developed an
      endoscopic pseudo-viewpoint alternation system with out any scope action. We
      investigate the effect of this novel system on forceps manipulation among expert
      pediatric surgeons. METHODS: Six expert pediatric surgeons performed a Nissen
      wrap in a fundoplication simulator either with or without this system. The
      constructed Nissen wrap was evaluated. The total path length and the average
      velocity of the forceps were also analyzed. RESULTS: The times required either
      with or without this system were 587.5 +/- 122.7 and 634.0 +/- 212.4 s (p =
      0.45), respectively. The total path lengths of right and left forceps either with
      or without this system were 12,309 +/- 2495.5 and 15,726 +/- 5649.6 mm (p =
      0.07), 10,091 +/- 2439.2 and 12,575 +/- 5511.1 mm (p = 0.11), respectively. The
      average velocity of the right and left forceps with or without this system were
      26.9 +/- 5.29 and 31.6 +/- 1.62 mm/s (p = 0.04), 21.6 +/- 2.48 and 25.5 +/- 6.48
      mm/s (p = 0.15), respectively. There was no significance in the suture balance
      and suture interval. CONCLUSION: The endoscopic pseudo-viewpoint alternation
      system thus made it possible for expert pediatric surgeons to carry out slow and
      economical forceps manipulation. These effects make it possible for surgeons to
      perform safe and precise surgery, thus leading to a shortening of operation time.

PMID- 26306420
TI  - Management of large primary spontaneous pneumothorax in children: radiological
      guidance, surgical intervention and proposed guideline.
AB  - PURPOSE: Primary spontaneous pneumothorax (PSP) is managed in accordance with the
      adult British Thoracic Society (BTS) guidelines due to lack of paediatric
      evidence and consensus. We aim to highlight the differences and provide a best
      practice surgical management strategy for PSP based on experience of two major
      paediatric surgical centres. METHODS: Retrospective review of PSP management and
      outcomes from two UK Tertiary Paediatric hospitals between 2004 and 2015.
      RESULTS: Fifty children with 55 PSP (5 bilateral) were referred to our Thoracic
      Surgical Services after initial management: 53% of the needle aspirations failed.
      Nine children (20%) were associated with visible bullae on the initial chest X
      ray. Forty-nine children were assessed with computed tomography scan (CT). Apical
      emphysematous-like changes (ELC) were identified in 37 children (75%). Ten
      children had also bullae in the asymptomatic contralateral lungs (20%). In two
      children (4%), CT demonstrated other lung lesions: a tumour of the left main
      bronchus in one child; a multi-cystic lesion of the right middle lobe in keeping
      with a congenital lung malformation in another child. Contralateral asymptomatic
      ELC were detected in 20% of the children: of those 40% developed pneumothorax
      within 6 months. Best surgical management was thoracoscopic staple bullectomy and
      pleurectomy with 11% risk of recurrence. Histology confirmed ELC in 100% of the
      apical lung wedge resections even in those apexes apparently normal at the time
      of thoracoscopy. CONCLUSION: Our experience suggests that adult BTS guidelines
      are not applicable to children with large PSP. Needle aspiration is ineffective.
      We advocate early referral to a Paediatric Thoracic Service. We suggest early
      chest CT scan to identify ELC, for counselling regarding contralateral
      asymptomatic ELC and to rule out secondary pathological conditions causing
      pneumothorax. In rare instance if bulla is visible on presenting chest X-ray,
      thoracoscopy could be offered as primary option.

PMID- 26306421
TI  - Validation of the PHQ-2 against the PHQ-9 for detecting depression in a large
      sample of Australian general practice patients.
AB  - There is increasing interest in the use of brief screening tools to improve
      detection of depression in the primary care setting. The aim of the present study
      was to compare the accuracy of the two-item Patient Health Questionnaire (PHQ-2)
      against the nine-item Patient Health Questionnaire (PHQ-9) for detecting
      depression among general practice patients. A cross-sectional sample of 3626
      adults attending 12 Australian general practices was recruited. Participants
      completed the PHQ-2 and PHQ-9 via a touchscreen computer. Depression was defined
      as a PHQ-9 score >=10. The area under the curve (AUC), sensitivity, specificity,
      positive predictive value and negative predictive value were calculated. The PHQ
      2 had good overall accuracy relative to the PHQ-9 for discriminating between
      cases and non-cases of depression, with an AUC of 0.92 (95% confidence interval
      0.90-0.93). The PHQ-2 threshold of >=3 was the best balance between sensitivity
      (91%) and specificity (78%) for detecting possible cases of depression. For
      clinical use, the optimal threshold was >=2, with only 2% of possible cases
      missed. 

PMID- 26306422
TI  - p53 modulates NF-kappaB mediated epithelial-to-mesenchymal transition in head and
      neck squamous cell carcinoma.
AB  - OBJECTIVES: To investigate the role of p53 in NF-kappaB mediated epithelial-to
      mesenchymal (EMT) in head and neck squamous cell carcinoma (HNSCC). MATERIALS AND
      METHODS: We utilized HNSCC and normal oral epithelial cell lines as our model
      system. We used a lentiviral shRNA system to silence the expression of p65 and
      p53 in these cell lines. Mutant and wild-type (WT) p53 background genotypes were
      analyzed. The expression of epithelial and mesenchymal markers was determined
      using western blotting and quantitative PCR assays. Cell morphology, growth, and
      invasion were determined using a 3-dimensional spheroid culture and anchorage
      independent growth (AIG) assays. RESULTS: In HNSCC cells with mutant p53 we found
      that silencing p65 expression promoted EMT. In contrast, in the context of WT
      p53, ectopic p65 over-expression promoted EMT. Ablation of WT p53 in normal oral
      epithelial cells blocked EMT induced by p65 over-expression. We demonstrate that
      AIG and apoptosis induced by NF-kappaB activation is regulated by p53.
      CONCLUSION: Our data demonstrates that p53 mutational status is critical in
      determining the outcome of NF-kappaB activation in HNSCC. In the presence of WT
      p53, excess p65 signal can promote EMT. Conversely, ablation of p65 in the
      context of mutant p53 drives EMT. These results demonstrate that p53 mutational
      status alters the outcome of NF-kappaB signaling. These results, though
      preliminary, demonstrate the critical role of p53 mutational status in
      determining the outcome of NF-kappaB signaling and suggest that monitoring p53
      status may inform the utility of NF-kappaB inhibitor treatment in HNSCC.

PMID- 26306423
TI  - BRAF p.V600E mutations are not unique to ameloblastoma and are shared by other
      odontogenic tumors with ameloblastic morphology.

PMID- 26306424
TI  - Perception of material properties.

PMID- 26306425
TI  - Analysis of EV71 infection progression using triple-SILAC-based proteomics
      approach.
AB  - Enterovirus 71 (EV71), a member of Picornaviridae, causes severe neurological and
      systemic illness in children. To better understand the virus-host cell
      interactions, we performed a triple-SILAC-based quantitative proteomics study
      monitoring host cell proteome changes after EV71 infection. Based on the
      quantitative data for more than 4100 proteins, ~17% of the proteins were found as
      significantly changed (p<0.01) at either 8 or 20 hours post infection. Five
      biological processes and seven protein classes showed significant differences.
      Functional screening of nine regulated proteins discovered the regulatory role of
      CHCH2, a mitochondrial protein known as a transcriptional activator for
      cytochrome c oxidase, in EV71 replication. Further studies showed that CHCH2
      served as a negative regulator of innate immune responses. All MS data have been
      deposited in the ProteomeXchange with identifier PXD002483
      (http://proteomecentral.proteomexchange.org/dataset/PXD002483). 

PMID- 26306426
TI  - Identification of putative target genes of bZIP19, a transcription factor
      essential for Arabidopsis adaptation to Zn deficiency in roots.
AB  - Zinc (Zn) depletion adversely affects plant growth. To avoid lethal depletion of
      cellular Zn, plants have evolved mechanisms to adjust the expression of genes
      associated with Zn homeostasis, the details of which are poorly understood. In
      the present study, we isolated an Arabidopsis thaliana T-DNA insertion mutant
      that exhibited hypersensitivity to Zn depletion. By monitoring root development
      under Zn-deficient conditions, we isolated a single mutant lacking the basic
      region leucine-zipper transcription factor gene bZIP19. To identify proteins
      whose expression is affected by bZIP19, an iTRAQ-based quantitative proteomics
      analysis was performed using microsomal proteins from wild-type and the bzip19
      mutant A. thaliana roots grown on Basal and Zn-deficient media. Of the 797
      proteins identified, expression of two members of the Zrt- and Irt-related
      protein family, ZIP3 and ZIP9, and three defensin-like family proteins was
      markedly induced in wild-type but not in the bzip19 mutant under Zn-deficient
      conditions. Furthermore, selected reaction monitoring and quantitative real-time
      PCR revealed that ZIP9 expression is mediated by bZIP19 and may be partly
      supported by bZIP23, a homolog of bZIP19. Mutant analysis revealed that ZIP9 is
      involved in uptake of Zn by the roots, and the mutant lacking ZIP9 was
      significantly more sensitive to Zn depletion than the wild-type. These results
      demonstrate that bZIP19 mainly contributes to expression of genes, such as ZIP9,
      under Zn-deficient conditions.

PMID- 26306427
TI  - Disposable Plasmonics: Plastic Templated Plasmonic Metamaterials with Tunable
      Chirality.
AB  - Development of low-cost disposable plasmonic substrates is vital for the
      applicability of plasmonic sensing. Such devices can be made using injection
      molded templates to create plasmonic films. The elements of these plasmonic films
      are hybrid nanostructures composed of inverse and solid structures. Tuning the
      modal coupling between the two allows optimization of the optical properties for
      nanophotonic applications. 

PMID- 26306429
TI  - Redox-neutral rhodium-catalyzed C-H functionalization of arylamine N-oxides with
      diazo compounds: primary C(sp(3))-H/C(sp(2))-H activation and oxygen-atom
      transfer.
AB  - An unprecedented rhodium(III)-catalyzed regioselective redox-neutral annulation
      reaction of 1-naphthylamine N-oxides with diazo compounds was developed to afford
      various biologically important 1H-benzo[g]indolines. This coupling reaction
      proceeds under mild reaction conditions and does not require external oxidants.
      The only by-products are dinitrogen and water. More significantly, this reaction
      represents the first example of dual functiaonalization of unactivated a primary
      C(sp(3) )?H bond and C(sp(2) )?H bond with diazocarbonyl compounds. DFT
      calculations revealed that an intermediate iminium is most likely involved in the
      catalytic cycle. Moreover, a rhodium(III)-catalyzed coupling of readily available
      tertiary aniline N-oxides with alpha-diazomalonates was also developed under
      external oxidant-free conditions to access various aminomandelic acid derivatives
      by an O-atom-transfer reaction. 

PMID- 26306428
TI  - Modulating RNA Alignment Using Directional Dynamic Kinks: Application in
      Determining an Atomic-Resolution Ensemble for a Hairpin using NMR Residual
      Dipolar Couplings.
AB  - Approaches that combine experimental data and computational molecular dynamics
      (MD) to determine atomic resolution ensembles of biomolecules require the
      measurement of abundant experimental data. NMR residual dipolar couplings (RDCs)
      carry rich dynamics information, however, difficulties in modulating overall
      alignment of nucleic acids have limited the ability to fully extract this
      information. We present a strategy for modulating RNA alignment that is based on
      introducing variable dynamic kinks in terminal helices. With this strategy, we
      measured seven sets of RDCs in a cUUCGg apical loop and used this rich data set
      to test the accuracy of an 0.8 MUs MD simulation computed using the Amber ff10
      force field as well as to determine an atomic resolution ensemble. The MD
      generated ensemble quantitatively reproduces the measured RDCs, but selection of
      a sub-ensemble was required to satisfy the RDCs within error. The largest
      discrepancies between the RDC-selected and MD-generated ensembles are observed
      for the most flexible loop residues and backbone angles connecting the loop to
      the helix, with the RDC-selected ensemble resulting in more uniform dynamics.
      Comparison of the RDC-selected ensemble with NMR spin relaxation data suggests
      that the dynamics occurs on the ps-ns time scales as verified by measurements of
      R(1rho) relaxation-dispersion data. The RDC-satisfying ensemble samples many
      conformations adopted by the hairpin in crystal structures indicating that
      intrinsic plasticity may play important roles in conformational adaptation. The
      approach presented here can be applied to test nucleic acid force fields and to
      characterize dynamics in diverse RNA motifs at atomic resolution.

PMID- 26306430
TI  - Assessment of Diffuse Thyroid Disease by Strain Ratio in Ultrasound Elastography.
AB  - The goal of this study was to explore the value of strain ratio from real-time
      elastography in the semi-quantitative assessment of diffuse thyroid disease.
      Fifty-one patients with primary hyperthyroidism, 70 with Hashimoto's thyroiditis,
      8 with subacute thyroiditis and 43 with normal healthy thyroids were recruited to
      measure the strain ratio (SR) of thyroid tissue and sternocleidomastoid muscle
      (on the same side of the thyroid). SR values of all groups were subjected to
      statistical analysis. The SRs (mean +/- standard deviation) of patients with
      hyperthyroidism, Hashimoto's thyroiditis and subacute thyroiditis were 2.30 +/-
      1.08, 7.04 +/- 7.74 and 24.09 +/- 13.56, respectively. The SR of the control
      group was 1.76 +/- 0.54. SR values ranked in ascending order were control group <
      hyperthyroidism group < Hashimoto's thyroiditis group < subacute thyroiditis
      group. There were statistically significant (p < 0.05) differences in thyroid
      hardness between groups with different diffuse thyroid diseases. SR values of the
      hyperthyroidism and control groups did not statistically differ (p > 0.05). It is
      feasible to assess diffuse thyroid disease with strain ratios obtained with
      ultrasound elastography. 

PMID- 26306431
TI  - Transforming Growth Factor beta1 Could Influence Thyroid Nodule Elasticity and
      Also Improve Cervical Lymph Node Metastasis in Papillary Thyroid Carcinoma.
AB  - Ultrasound elastography has been a very useful tool in predicting the risk of
      malignant thyroid tumor for several years. The objective of this study was to
      determine if there is a correlation between strain ratio (SR), collagen
      deposition and transforming growth factor beta1 (TGF-beta1) expression in
      different types of thyroid nodules and if TGF-beta1 is related to cervical lymph
      node metastasis. 102 nodules from 81 patients who underwent thyroid resection
      surgery in our hospital were retrospectively studied. All of these patients had
      undergone ultrasound elastography scanning before surgery. Masson staining and
      immunohistochemical staining were used to evaluate the ratio of expression of
      collagen deposition and TGF-beta1. There was a significant difference between
      benign and malignant thyroid nodules in SR (8.913 +/- 11.021 vs. 1.732 +/- 0.727,
      p = 0.000), collagen content (0.371 +/- 0.125 vs. 0.208 +/- 0.057, p = 0.000) and
      TGF-beta1 expression (0.336 +/- 0.093 vs. 0.178 +/- 0.071, p = 0.000). A cutoff
      of 2.99 for SR measurement was selected for the highest Youden index for
      predicting malignant thyroid nodules, which yielded 87.88% sensitivity, 100%
      specificity, 100% positive predictive value, 83.72% negative predictive value and
      92.15% accuracy. Expression of collagen and TGF-beta1 was positively correlated
      with SR measurements (coefficient = 0.839 for collagen and 0.855 for TGF-beta1, p
      = 0.000). Among 61 nodules with papillary thyroid carcinoma, the average SR for
      the metastasis group was higher than that for the non-metastasis group (10.955 +/
      13.805 and 7.852 +/- 7.931, respectively), but without statistical significance
      (p = 0.287). Collagen deposition was significantly higher in the metastasis group
      than in the non-metastasis group (0.421 +/- 0.091 vs. 0.353 +/- 0.118, p =
      0.011). TGF-beta1 expression was also significantly higher in the metastasis
      group than in the non-metastasis group (0.378 +/- 0.0.69 vs. 0.328 +/- 0.091, p =
      0.016). To conclude, TGF-beta1 may contribute to thyroid nodule elasticity by
      promoting collagen deposition. In papillary thyroid carcinoma, overexpression of
      TGF-beta1, as well as collagen deposition, may be a risk factor for cervical
      lymph node metastasis.

PMID- 26306432
TI  - CT versus grayscale rib series for the detection of rib fracture.

PMID- 26306433
TI  - Impact of individual characteristics on sonographic IVC diameter and the IVC
      diameter/aorta diameter index.
AB  - BACKGROUND: The inferior vena cava (IVC) parameters, including its diameter and
      collapsibility index have been evaluated for fluid status for over 30 years, but
      little is known about the impacts of patient characteristics on IVC parameters.
      The purpose of this study was to explore the relationships between individual
      patient characteristics and IVC parameters in healthy Chinese adult volunteers.
      METHODS: From February 2012 to May 2012, 216 healthy volunteers older than the
      age of 18 years were consecutively enrolled in our study. The individual
      characteristics and presence or absence of hypertension of each participant were
      recorded. Sonographic measurements of IVC and abdominal aorta diameter (Ao) were
      performed (DP-6900; Mindray, Shenzhen, China). RESULTS: Volunteers ranged in age
      from 18 to 84 years (43.7 +/- 7.8 years), and 50.5% were males. In univariate
      analyses, maximum IVC diameter (IVCmax) was negatively correlated with age
      (years) (r = -0.171, P = .012) and positively correlated with sex (men) (r =
      0.174, P = .01), height (centimeters) (r = 0.281, P < .001), and body surface
      area (square meters) (r = 0.173, P = .011). The IVC/Ao index was negatively
      correlated with age (years) (r = -0.326, P < .001), waist circumference
      (centimeters) (r = -0.176, P = .01), body mass index (r = -0.173, P = .011), and
      hypertension (r = -0.186, P = .006). None of the patient characteristics were
      significantly correlated with percentage collapse of the IVC. Height
      (centimeters) was the sole significant predictor of IVCmax (R(2) = 0.079, P <
      .001). Age (years) and body mass index (kilogram/square meter) were independent
      predictors of the IVC/Ao index (R(2) = 0.123; P < .001 and P = .046,
      respectively). CONCLUSIONS: The percentage collapse of IVC and the IVCmax are not
      substantially influenced by patient characteristics. In contrast, the IVC/Ao
      index is more susceptible to patient characteristics than IVC.

PMID- 26306435
TI  - Motion analysis of cardiopulmonary resuscitation.
AB  - OBJECTIVE: Some cardiopulmonary resuscitation (CPR) monitoring devices were
      released in recent years. Some of them are motion sensors. There are no
      guidelines were to position future or present sensors during CPR. We evaluate the
      possible influence of the location of motion sensors by a high-speed camera
      during a CPR on a manikin. MATERIAL AND METHODS: We performed a motion analysis
      by a high-speed camera during chest compression (CC) on a manikin to quantify
      chest inhomogeneous displacements and rescuer motion. RESULTS: Midline chest was
      found to have an inhomogeneous depth during CC (19 mm for the upper sternum, 27
      mm for the middle of the sternum, and 47 mm for the xiphoid). Rescuer anatomy has
      a complex motion. CONCLUSION: The direct application of the sensor under the hand
      performing CC seems to be the more accurate solution if the device allows it.

PMID- 26306434
TI  - Opiate refractory pain from an intestinal obstruction responsive to an
      intravenous lidocaine infusion.
AB  - A 24-year-old female patient presented to our community emergency department (ED)
      for abdominal pain that had progressively worsened over the last 28 hours. Of
      note, 1 month prior to her presentation, the patient had a colostomy due to a
      rectal abscess and required stoma revision 5 days prior to her visit to our ED.
      The patient's pain was refractory to opiate analgesia in our ED, but experienced
      significant relief after an intravenous lidocaine infusion. Computer tomography
      of the abdomen and pelvis ultimately revealed a large bowel obstruction just
      proximal to the colostomy site. Historically, options for ED management of severe
      pain have been limited beyond narcotic analgesia. For patients whom are
      refractory to opiates in the ED, or for whom opiates are contraindicated,
      lidocaine infusions have shown promise for a variety of both acute and chronic
      painful conditions.

PMID- 26306436
TI  - Clinical application of real-time tele-ultrasonography in diagnosing pediatric
      acute appendicitis in the ED.
AB  - PURPOSE: We investigated the effectiveness of tele-mentored ultrasonography
      between emergency medicine (EM) residents and remote experts in diagnosing acute
      appendicitis. METHODS: This prospective observational study was performed in an
      academic emergency department. Beginning in June 2014, the EM residents performed
      the initial ultrasonography for suspected pediatric acute appendicitis; then, the
      remote experts observed/mentored the residents' practice using the tele
      ultrasonography system; and finally, an onsite expert verified the diagnosis. The
      diagnostic confidence of each examiner (resident, remote expert, and onsite
      expert) was rated on a 5-point Likert scale. The appendix identification rate and
      the diagnostic values; sensitivity, specificity, positive predictive value (PPV)
      and negative predictive value (NPV) for each type of examination were calculated.
      RESULTS: A total of 115 pediatric cases with suspected acute appendicitis,
      including 36 with pathology-confirmed acute appendicitis, between June 2014 and
      February 2015 were enrolled in this study. In 9 of the 115 (7.8%) cases, a non
      appendicitis diagnosis was determined in the absence of the successful
      identification of a normal appendix upon resident examination. Of these, seven
      appendices were identified upon expert tele-ultrasonography. The diagnostic
      values for expert tele-ultrasonography were higher (sensitivity: 1.000,
      specificity: 0.975, PPV: 0.947, NPV: 1.000) than those for resident-performed
      ultrasonography (sensitivity: 0.917, specificity: 0.899, PPV: 0.805, NPV: 0.959)
      and similar to those for onsite expert-performed ultrasonography (sensitivity:
      1.000, specificity: 0.987, PPV: 0.973, NPV: 1.000). CONCLUSION: Tele
      ultrasonography with tele-mentoring between EM residents and experienced mentors
      was effectively applied in diagnosing pediatric acute appendicitis in an
      emergency clinical setting.

PMID- 26306437
TI  - Should laryngeal tubes or masks be used for out-of-hospital cardiac arrest
      patients?
AB  - OBJECTIVE: Few studies have compared airway management via laryngeal masks (LM)
      or laryngeal tubes (LT) in patients with out-of-hospital cardiac arrest (OHCA).
      This study evaluated whether LT insertion by emergency medical service (EMS)
      personnel affected ventilation and outcomes in OHCA patients (vs. the standard LM
      treatment). METHODS: This prospective, cluster-randomized, and open-label study
      evaluated data that were collected by the Sapporo Fire Department between June
      2012 and January 2013. We selected the 14 EMS teams that treated the greatest
      number of OHCA patients in Sapporo, Japan during 2011, and randomized the teams
      into Groups A and B. In the first study period (June 2012 to September 2012),
      Group A treated OHCA patients via LT and Group B treated OHCA patients via LM. In
      the second period (October 2012 to January 2013), Group A treated OHCA patients
      via LM and Group B treated OHCA patients via LT. If necessary, both groups were
      allowed to use an esophageal obturator airway (EOA) kit. The primary endpoints
      were time from cardiopulmonary resuscitation to device insertion and the rate of
      successful pre-hospital ventilation. The secondary endpoints were return of
      spontaneous circulation and survival and favorable neurological outcomes at 1
      month after cardiac arrest. RESULTS: LT was used in 148 OHCA patients and LM was
      used in 165 OHCA patients. Our intention-to-treat analyses revealed no
      significant differences in the primary and secondary outcomes of the LT- and LM
      treated groups. CONCLUSION: Prehospital advanced airway management via LT
      provides similar outcomes to those of LM in OHCA patients.

PMID- 26306438
TI  - A rare cause of 2:1 atrioventricular block: carbamazepine.
AB  - We report a case of carbamazepine-induced 2:1 atrioventricular (AV) block. A 56
      year-old man was admitted to our emergency department for recurrent attacks of
      dizziness and syncope. His serum carbamazepine level was within therapeutic
      range, and his electrocardiogram revealed 2:1 AV block. After withdrawal of
      carbamazepine therapy, the arrhythmia completely resolved. This report suggests
      that carbamazepine-induced AV block can occur even in therapeutic serum
      concentrations and that it can be reversible.

PMID- 26306440
TI  - Thromboinflammation in Therapeutic Medicine.
AB  - Thromboinflammation is primarily triggered by the humoral innate immune system,
      which mainly consists of the cascade systems of the blood, i.e., the complement,
      contact/coagulation and fibrinolytic systems. Activation of these systems
      subsequently induces activation of endothelial cells, leukocytes and platelets,
      finally resulting in thrombotic and inflammatory reactions. Such reactions are
      triggered by a number of medical procedures, e.g., treatment with biomaterials or
      drug delivery devices as well as in transplantation with cells, cell clusters or
      whole vascularized organs. Here, we (1) describe basic mechanisms for
      thromboinflammation; (2) review thromboinflammatory reactions in therapeutic
      medicine; and (3) discuss emerging strategies to dampen thromboinflammation. 

PMID- 26306441
TI  - Complement Interactions with Blood Cells, Endothelial Cells and Microvesicles in
      Thrombotic and Inflammatory Conditions.
AB  - The complement system is activated in the vasculature during thrombotic and
      inflammatory conditions. Activation may be associated with chronic inflammation
      on the endothelial surface leading to complement deposition. Complement mutations
      allow uninhibited complement activation to occur on platelets, neutrophils,
      monocytes, and aggregates thereof, as well as on red blood cells and endothelial
      cells. Furthermore, complement activation on the cells leads to the shedding of
      cell derived-microvesicles that may express complement and tissue factor thus
      promoting inflammation and thrombosis. Complement deposition on red blood cells
      triggers hemolysis and the release of red blood cell-derived microvesicles that
      are prothrombotic. Microvesicles are small membrane vesicles ranging from 0.1 to
      1 MUm, shed by cells during activation, injury and/or apoptosis that express
      components of the parent cell. Microvesicles are released during inflammatory and
      vascular conditions. The repertoire of inflammatory markers on endothelial cell
      derived microvesicles shed during inflammation is large and includes complement.
      These circulating microvesicles may reflect the ongoing inflammatory process but
      may also contribute to its propagation. This overview will describe complement
      activation on blood and endothelial cells and the release of microvesicles from
      these cells during hemolytic uremic syndrome, thrombotic thrombocytopenic purpura
      and vasculitis, clinical conditions associated with enhanced thrombosis and
      inflammation. 

PMID- 26306439
TI  - Neuroinflammation: Ways in Which the Immune System Affects the Brain.
AB  - Neuroinflammation is the response of the central nervous system (CNS) to
      disturbed homeostasis and typifies all neurological diseases. The main reactive
      components of the CNS include microglial cells and infiltrating myeloid cells,
      astrocytes, oligodendrocytes, and the blood-brain barrier, cytokines, and
      cytokine signaling. Neuroinflammatory responses may be helpful or harmful, as
      mechanisms associated with neuroinflammation are involved in normal brain
      development, as well as in neuropathological processes. This review examines the
      roles of various cell types that contribute to the immune dysregulation
      associated with neuroinflammation. Microglia enter the CNS very early in
      embryonic development and, as such, play an essential role in both the healthy
      and diseased brain. B-cell diversity contributes to CNS disease through both
      antibody-dependent and antibody-independent mechanisms. The influences of these B
      cell mechanisms on other cell types, including myeloid cells and T cells, are
      reviewed in relationship to antibody-mediated CNS disorders, paraneoplastic
      neurological diseases, and multiple sclerosis. New insights into
      neuroinflammation offer exciting opportunities to investigate potential
      therapeutic targets for debilitating CNS diseases.

PMID- 26306442
TI  - Role of Complement on Broken Surfaces After Trauma.
AB  - Activation of both the complement and coagulation cascade after trauma and
      subsequent local and systemic inflammatory response represent a major scientific
      and clinical problem. After severe tissue injury and bone fracture, exposure of
      innate immunity to damaged cells and molecular debris is considered a main
      trigger of the posttraumatic danger response. However, the effects of cellular
      fragments (e.g., histones) on complement activation remain enigmatic.
      Furthermore, direct effects of "broken" bone and cartilage surfaces on the fluid
      phase response of complement and its interaction with key cells of connective
      tissues are still unknown. Here, we summarize data suggesting direct and indirect
      complement activation by extracellular and cellular danger associated molecular
      patterns. In addition, key complement components and the corresponding receptors
      (such as C3aR, C5aR) have been detected on "exposed surfaces" of the damaged
      regions. On a cellular level, multiple effects of complement activation products
      on osteoblasts, osteoclasts, chondrocytes and mesenchymal stem cells have been
      found.In conclusion, the complement system may be activated by trauma-altered
      surfaces and is crucially involved in connective tissue healing and posttraumatic
      systemic inflammatory response. 

PMID- 26306444
TI  - The Lectin Pathway of Complement and Biocompatibility.
AB  - In modern health technologies the use of biomaterials in the form of stents,
      haemodialysis tubes, artificial implants, bypass circuits etc. is rapidly
      expanding. The exposure of synthetic, foreign surfaces to the blood and tissue of
      the host, calls for strict biocompatibility in respect to contact activation, the
      coagulation system and the complement system. The complement system is an
      important part of the initial immune response and consists of fluid phase
      molecules in the blood stream. Three different activation pathways can initiate
      the complement system, the lectin, the classical and the alternative pathway, all
      converging in an amplification loop of the cascade system and downstream
      reactions. Thus, when exposed to foreign substances complement components will be
      activated and lead to a powerful inflammatory response. Biosurface induced
      complement activation is a recognised issue that has been broadly documented.
      However, the specific role of lectin pathway and the pattern recognition
      molecules initiating the pathway has only been transiently investigated. Here we
      review the current data on the field. 

PMID- 26306445
TI  - Foreign Body Reaction to Subcutaneous Implants.
AB  - Subcutaneously implanted materials trigger the host's innate immune system,
      resulting in the foreign body reaction. This reaction consists of protein
      adsorption on the implant surface, inflammatory cell infiltration, macrophage
      fusion into foreign body giant cells, fibroblast activation and ultimately
      fibrous encapsulation. This series of events may affect the function of
      subcutaneous implants, such as inhibition of drug diffusion from long-acting drug
      delivery depots and medical device failure. The foreign body reaction is a
      complex phenomenon and is not yet fully understood; ongoing research studies aim
      to elucidate the cellular and molecular dynamics involved. Recent studies have
      revealed information about the specific role of macrophages and their
      differential activation towards pro- and anti-inflammatory states, as well as
      species differences in the timing of collagen deposition and fibrosis.
      Understanding of the diverse processes involved in the foreign body reaction has
      led to multiple approaches towards its negation. Delivery of tissue response
      modifiers, such as corticosteroids, NSAIDs, antifibrotic agents, and siRNAs, has
      been used to prevent or minimize fibrosis. Of these, delivery of dexamethasone
      throughout the implantation period is the most common method to prevent
      inflammation and fibrosis. More recent approaches employ surface modifications to
      minimize protein adsorption to 'ultra-low' levels and reduce fibrosis. However,
      the diverse nature of the processes involved in the foreign body reaction favor
      the use of corticosteroids due to their wide spectrum action compared to other
      approaches. To date, combination approaches, such as hydrophilic coatings that
      reduce protein adsorption combined with delivery of dexamethasone are the most
      effective. 

PMID- 26306443
TI  - Complement Involvement in Periodontitis: Molecular Mechanisms and Rational
      Therapeutic Approaches.
AB  - The complement system is a network of interacting fluid-phase and cell surface
      associated molecules that trigger, amplify, and regulate immune and inflammatory
      signaling pathways. Dysregulation of this finely balanced network can destabilize
      host-microbe homeostasis and cause inflammatory tissue damage. Evidence from
      clinical and animal model-based studies suggests that complement is implicated in
      the pathogenesis of periodontitis, a polymicrobial community-induced chronic
      inflammatory disease that destroys the tooth-supporting tissues. This review
      discusses molecular mechanisms of complement involvement in the dysbiotic
      transformation of the periodontal microbiome and the resulting destructive
      inflammation, culminating in loss of periodontal bone support. These mechanistic
      studies have additionally identified potential therapeutic targets. In this
      regard, interventional studies in preclinical models have provided proof-of
      concept for using complement inhibitors for the treatment of human periodontitis.

PMID- 26306448
TI  - Xenotransplantation of Cells, Tissues, Organs and the German Research Foundation
      Transregio Collaborative Research Centre 127.
AB  - Human organ transplantation is the therapy of choice for end-stage organ failure.
      However, the demand for organs far exceeds the donation rate, and many patients
      die while waiting for a donor. Clinical xenotransplantation using discordant
      species, particularly pigs, offers a possible solution to this critical
      shortfall. Xenotransplantation can also increase the availability of cells, such
      as neurons, and tissues such as cornea, insulin producing pancreatic islets and
      heart valves. However, the immunological barriers and biochemical disparities
      between pigs and primates (human) lead to rejection reactions despite the use of
      common immunosuppressive drugs. These result in graft vessel destruction,
      haemorrhage, oedema, thrombus formation, and transplant loss. Our consortium is
      pursuing a broad range of strategies to overcome these obstacles. These include
      genetic modification of the donor animals to knock out genes responsible for
      xenoreactive surface epitopes and to express multiple xenoprotective molecules
      such as the human complement regulators CD46, 55, 59, thrombomodulin and others.
      We are using (new) drugs including complement inhibitors (e.g. to inhibit C3
      binding), anti-CD20, 40, 40L, and also employing physical protection methods such
      as macro-encapsulation of pancreatic islets. Regarding safety, a major objective
      is to assure that possible infections are not transmitted to recipients. While
      the aims are ambitious, recent successes in preclinical studies suggest that
      xenotransplantation is soon to become a clinical reality. 

PMID- 26306446
TI  - Molecular Characterization of Macrophage-Biomaterial Interactions.
AB  - Implantation of biomaterials in vascularized tissues elicits the sequential
      engagement of molecular and cellular elements that constitute the foreign body
      response. Initial events include the non-specific adsorption of proteins to the
      biomaterial surface that render it adhesive for cells such as neutrophils and
      macrophages. The latter undergo unique activation and in some cases undergo cell
      cell fusion to form foreign body giant cells that contribute to implant damage
      and fibrotic encapsulation. In this review, we discuss the molecular events that
      contribute to macrophage activation and fusion with a focus on the role of the
      inflammasome, signaling pathways such as JAK/STAT and NF-kappaB, and the putative
      involvement of micro RNAs in the regulation of these processes. 

PMID- 26306449
TI  - Macroencapsulated Pig Islets Correct Induced Diabetes in Primates up to 6 Months.
AB  - A bioartificial pancreas, in which islets of Langerhans are encapsulated within a
      semipermeable membrane, may be an alternative therapeutic device for diabetic
      patients. It may constitute another safe and simple method of transplanting
      islets without the need for immunosuppressive therapy. Since the semipermeable
      membrane protects the islets from the host immune system, the islets are likely
      to survive and release insulin for a long period of time, thereby controlling
      glucose metabolism in the absence of immunosuppressive medication. Recent data
      using macroencapsulation of pig islets in primate seems encouraging. In fact, a
      "mono/bilayer" configuration of macroencapsulated pig islets implanted
      subcutaneously has been found to significantly improve diabetes control in
      primates for 6 months without any immunosuppression. 

PMID- 26306447
TI  - Heparan Sulfate Proteoglycan Metabolism and the Fate of Grafted Tissues.
AB  - Tissue and organ transplants between genetically distinct individuals are always
      or nearly always rejected. The universality and speed of transplant rejection
      distinguishes this immune response from all others. Although this distinction is
      incompletely understood, some efforts to shed light on transplant rejection have
      revealed broader insights, including a relationship between activation of
      complement in grafted tissues, the metabolism of heparan sulfate proteoglycan and
      the nature of immune and inflammatory responses that ensue. Complement activation
      on cell surfaces, especially on endothelial cell surfaces, causes the shedding
      heparan sulfate, an acidic saccharide, from the cell surface and neighboring
      extracellular matrix. Solubilized in this way, heparan sulfate can activate
      leukocytes via toll like receptor-4, triggering inflammatory responses and
      activating dendritic cells, which migrate to regional lymphoid organs where they
      spark and to some extent govern cellular immune responses. In this way local
      ischemia, tissue injury and infection, exert systemic impact on immunity. Whether
      or in what circumstances this series of events explains the distinct
      characteristics of the immune response to transplants is still unclear but the
      events offer insight into the inception of immunity under the sub-optimal
      conditions accompanying infection and mechanisms by which infection and tissue
      injury engender systemic inflammation. 

PMID- 26306450
TI  - Regulation of Instant Blood Mediated Inflammatory Reaction (IBMIR) in Pancreatic
      Islet Xeno-Transplantation: Points for Therapeutic Interventions.
AB  - Xeno-transplantation of pancreatic islets represents a promising therapeutic
      alternative for the treatment of type 1 diabetes mellitus. However, potent innate
      immune responses induced shortly after the transplantation of donor islets to the
      recipient, comprising the Instant Blood Mediated Immune Reaction (IBMIR), exert
      detrimental actions on islet graft function. The coagulation and complement
      cascades together with the leukocyte and platelet populations are the major
      players in IBMIR. This innate immune attack affects dramatically islet integrity
      and leads to significant loss of function of the xenograft. In the present
      review, we focus on the mechanisms contributing to IBMIR components and address
      therapeutic intervention approaches to limit IBMIR by administering inhibitors in
      circulation, by coating the islet surface with inhibitors or by generating
      transgenic donor animals; these approaches could result in improved xenograft
      survival. 

PMID- 26306451
TI  - Cell Surface Engineering for Regulation of Immune Reactions in Cell Therapy.
AB  - Transplantation of the pancreatic islets of Langerhans (islets) is a promising
      cell therapy for treating insulin-dependent type 1 diabetes mellitus. Islet
      transplantation is a minimally-invasive technique involving relatively simple
      surgery. However, after intraportal transplantation, the transplanted islets are
      attacked by the recipient's immune system, because they activate a number of
      systems, including coagulation, complement response, inflammation, immune
      rejection, and recurrence of autoimmune disease. We have developed a surface
      modification and microencapsulation technique that protects cells and islets with
      biomaterials and bioactive substances, which may be useful in clinical settings.
      This approach employs amphiphilic polymers, which can interact with lipid bilayer
      membranes, without increasing cell volume. Molecules attached to these polymers
      can protect transplanted cells and islets from attack by the host immune system.
      We expect that this surface modification technique will improve graft survival in
      clinical islet transplantation. 

PMID- 26306452
TI  - Complement Interception Across Humoral Incompatibility in Solid Organ
      Transplantation: A Clinical Perspective.
AB  - The humoral barrier in transplant biology is the result of preformed donor
      specific antibodies (DSAs), directed either against human leukocyte antigens
      (HLA) or non-HLA antigens such as blood group (ABO) molecules. The term
      "sensitization" applies to patients carrying these antibodies. Transplantation is
      widely accepted as a life-saving opportunity for patients with terminal end-organ
      disease. However, in sensitized patients, transplant outcome is hampered by
      antibody-mediated rejection (AMR) as a consequence of DSA exposure. Furthermore,
      sensitized patients have limited access to "matched" organs from the both living
      and deceased donor pool.Considering the crucial role of the complement system in
      the pathophysiology of AMR and the availability of complement intervention
      therapeutics, there is a growing interest in complement-targeting strategies.
      This review highlights the emerging importance of monitoring and modulation of
      the complement system in the context of enabling transplantation across humoral
      incompatibility in sensitized recipients with preformed anti-HLA or natural anti
      ABO antibodies. It also discusses the significance of the complement system in
      the induction of accommodation and further emphasizes current and future
      perspectives of novel complement therapeutics. 

PMID- 26306453
TI  - Killer immunoglobulin-like receptors can predict TKI treatment-free remission in
      chronic myeloid leukemia patients.
AB  - Several factors are predictive of treatment-free remission (TFR) in chronic
      myeloid leukemia (CML), but few data exist on the role of natural killer (NK)
      cells and their killer-cell immunoglobulin-like receptors (KIRs). KIR and human
      leukocyte antigen (HLA) genotypes were investigated in 36 CML patients who
      discontinued tyrosine kinase inhibitor (TKI) treatment after achieving deep
      molecular response (MR(4.5)). Cumulative TFR was significantly higher in patients
      homozygous for KIR A haplotype (85.7% vs. 45.5%; p = 0.029). Younger age, Bx
      haplotype, and the combination KIR3DS1/KIR3DL1 present/HLA-Bw4 present were
      significantly associated with relapse. KIR genotypes could prove useful in
      identifying patients that are likely to maintain MR(4.5) after discontinuing TKI
      treatment. 

PMID- 26306454
TI  - Short- and longer-term predictive capacity of the Multidimensional Prognostic
      Index: The timing of the assessment is of no consequence.
AB  - BACKGROUND: Several studies have tested the ability of the Multidimensional
      Prognostic Index (MPI) to predict mortality for acute elderly patients admitted
      to hospital. We compared the reliability of MPI scores obtained both on admission
      to, and at discharge from hospital. We tested MPI performance in predicting short
      and longer-term mortality grouped into three risk groups and according to single
      MPI scores. METHODS: A longitudinal prospective study was conducted on 699
      elderly patients admitted to the Geriatric Unit at Padua General Hospital. MPI
      scores were obtained on admission and at discharge. In-hospital and one-year
      mortality was recorded. Adjusted Cox's regression models were used to assess the
      prognostic value of the MPI scores. RESULTS: 691 were included in the study: 459
      (66.4%) women and 232 (33.6%) men, mean age=85.2 +/- 7.0 years. Patients were
      grouped as: low risk MPI 12.5%; moderate risk MPI 28.6%; severe risk MPI 58.9%.
      The cumulative in-hospital mortality rate was 7.4%. In the adjusted model, only
      MPI score (not MPI risk group) was significantly associated with in-hospital
      death ([HR]=1.22, 95%CI 1.07-1.39). 1-Year crude mortality rate: 39.2%. The
      patients' MPI scores at admission and at discharge were equally predictive of
      death (adjusted HR of MPI on admission 1.20 [1.15-1.27], p<0.0001; at discharge
      1.24 [1.18-1.30], p<0.0001). The performance (AUC) of the MPI score on admission
      and at discharge proved much the same. CONCLUSIONS: This study confirmed the
      value of the MPI in predicting mortality for acute elderly patients. Grouping MPI
      scores into risk levels may not be appropriate when applied to hospitalized acute
      geriatric patients. The prognostic value of MPI scores was confirmed only for MPI
      value >=0.68. Judging from our study, the timing of the assessment during a
      patient's hospital stay (on admission or at discharge) may be irrelevant for
      longer-term prognostic purposes.

PMID- 26306455
TI  - Concurrent Carotid Inflammation in Acute Coronary Syndrome as Assessed by (18)F
      FDG PET/CT: A Possible Mechanistic Link for Ischemic Stroke.
AB  - BACKGROUND: Patients with acute coronary syndrome (ACS) are prone to ischemic
      stroke (IS) especially during the early phase. ACS patients are more likely to
      have concurrent complex carotid plaques which, when destabilized, may serve as a
      source of distal embolism. This study investigated whether inflammatory activity
      in carotid artery was increased in ACS survivors compared to chronic stable
      angina (CSA) patients. METHODS: We prospectively enrolled 74 patients with ACS or
      CSA (39 ACS patients versus 35 CSA patients), and fluorodeoxyglucose positron
      emission tomography/computed tomography ((18)F-FDG PET/CT) was performed within 1
      week after diagnosis. Carotid PET signal was quantified as standardized uptake
      value (SUV) and target-to-background ratio (TBR, carotid SUV/jugular venous SUV).
      RESULTS: Baseline characteristics were similar between groups. TBRs and SUVs were
      significantly higher in the carotid arteries of ACS patients than those of CSA
      patients (P < .001). Systemic inflammatory biomarker correlated significantly
      with carotid FDG uptake (high-sensitivity C-reactive protein versus average SUV:
      r = .361, P = .002), and the presence of cardiovascular risk factors was also
      related to inflammation activity. During follow-up, 3 cerebrovascular events
      occurred in ACS patients (including 1 early IS in a patient with severe baseline
      carotid inflammation), whereas none in CSA patients (P = .057). CONCLUSIONS: This
      study provided in vivo evidence that ACS survivors might experience concurrent
      carotid arterial inflammation. Our findings supported the role of systemic immune
      activation contributing to multiarterial instability in symptomatic
      atherosclerosis as a possible mechanistic link between ACS and IS.

PMID- 26306456
TI  - Differences in ventricular tachyarrythmias and antitachycardia pacing
      effectiveness according to the ICD indication (primary versus secondary
      prevention): an analysis based on the stored electrograms.
AB  - PURPOSE: To determine whether monomorphic ventricular tachycardias (VTs) have
      different characteristics and/or responses to antitachycardia pacing (ATP) with
      respect to the indication-primary prevention (PP) versus secondary prevention
      (SP)-among ICD patients with left ventricular dysfunction. METHODS: We
      prospectively studied 551 VT (cycle length [CL] 329 +/- 35 ms; PP 34%) occurring
      in 67 ICD patients with left ventricular dysfunction (LVEF 35 +/- 8%). ICD
      programming was standardized, including ATP for slow (CL 400-321 ms) and fast VT
      (CL 250-320 ms). We analyzed the following aspects: CL, percentage of variability
      of the 12 RR intervals prior to ATP (P-RR)-which was calculated by dividing the
      mean difference between each R-R interval with the next one by the CL * 100-and
      type of termination: immediate (VT ceased immediately upon ATP completion) or
      delayed (VT persisted after ATP). RESULTS: ATP was successful in 86% of VTs. VTs
      occurring in SP patients had a lower P-RR, median (IQR) 2.7% (1.2-3.7) versus
      1.9% (0.9-3.2); p = 0.002; they terminated immediately after ATP less frequently
      (27% versus 12%; p < 0.001), and although they were more frequently slow (51%
      versus 67%; p = 0.01), ATP was less effective in them, 92 versus 80% (p = 0.02).
      CONCLUSIONS: VTs occurring in SP patients are slower, more stable, and they
      terminate less frequently at ATP. Therefore, compared with PP, SP patients seem
      to have fewer self-terminating VTs.

PMID- 26306458
TI  - MSIseq: Software for Assessing Microsatellite Instability from Catalogs of
      Somatic Mutations.
AB  - Microsatellite instability (MSI) is a form of hypermutation that occurs in some
      tumors due to defects in cellular DNA mismatch repair. MSI is characterized by
      frequent somatic mutations (i.e., cancer-specific mutations) that change the
      length of simple repeats (e.g., AAAAA...., GATAGATAGATA...). Clinical MSI tests
      evaluate the lengths of a handful of simple repeat sites, while next-generation
      sequencing can assay many more sites and offers a much more complete view of
      their somatic mutation frequencies. Using somatic mutation data from the exomes
      of a 361-tumor training set, we developed classifiers to determine MSI status
      based on four machine-learning frameworks. All frameworks had high accuracy, and
      after choosing one we determined that it had >98% concordance with clinical tests
      in a separate 163-tumor test set. Furthermore, this classifier retained high
      concordance even when classifying tumors based on subsets of whole-exome data. We
      have released a CRAN R package, MSIseq, based on this classifier. MSIseq is
      faster and simpler to use than software that requires large files of aligned
      sequenced reads. MSIseq will be useful for genomic studies in which clinical MSI
      test results are unavailable and for detecting possible misclassifications by
      clinical tests. 

PMID- 26306460
TI  - Developments in amphibian captive breeding and reintroduction programs.
AB  - Captive breeding and reintroduction remain high profile but controversial
      conservation interventions. It is important to understand how such programs
      develop and respond to strategic conservation initiatives. We analyzed the
      contribution to conservation made by amphibian captive breeding and
      reintroduction since the launch of the International Union for Conservation of
      Nature (IUCN) Amphibian Conservation Action Plan (ACAP) in 2007. We assembled
      data on amphibian captive breeding and reintroduction from a variety of sources
      including the Amphibian Ark database and the IUCN Red List. We also carried out
      systematic searches of Web of Science, JSTOR, and Google Scholar for relevant
      literature. Relative to data collected from 1966 to 2006, the number of species
      involved in captive breeding and reintroduction projects increased by 57% in the
      7 years since release of the ACAP. However, there have been relatively few new
      reintroductions over this period; most programs have focused on securing captive
      assurance populations (i.e., species taken into captivity as a precaution against
      extinctions in the wild) and conservation-related research. There has been a
      shift to a broader representation of frogs, salamanders, and caecilians within
      programs and an increasing emphasis on threatened species. There has been a
      relative increase of species in programs from Central and South America and the
      Caribbean, where amphibian biodiversity is high. About half of the programs
      involve zoos and aquaria with a similar proportion represented in specialist
      facilities run by governmental or nongovernmental agencies. Despite successful
      reintroduction often being regarded as the ultimate milestone for such programs,
      the irreversibility of many current threats to amphibians may make this an
      impractical goal. Instead, research on captive assurance populations may be
      needed to develop imaginative solutions to enable amphibians to survive alongside
      current, emerging, and future threats. 

PMID- 26306459
TI  - eIF4E/Fmr1 double mutant mice display cognitive impairment in addition to ASD
      like behaviors.
AB  - Autism spectrum disorder (ASD) is a group of heritable disorders with complex and
      unclear etiology. Classic ASD symptoms include social interaction and
      communication deficits as well as restricted, repetitive behaviors. In addition,
      ASD is often comorbid with intellectual disability. Fragile X syndrome (FXS) is
      the leading genetic cause of ASD, and is the most commonly inherited form of
      intellectual disability. Several mouse models of ASD and FXS exist, however the
      intellectual disability observed in ASD patients is not well modeled in mice.
      Using the Fmr1 knockout mouse and the eIF4E transgenic mouse, two previously
      characterized mouse models of fragile X syndrome and ASD, respectively, we
      generated the eIF4E/Fmr1 double mutant mouse. Our study shows that the eIF4E/Fmr1
      double mutant mice display classic ASD behaviors, as well as cognitive
      dysfunction. Importantly, the learning impairments displayed by the double mutant
      mice spanned multiple cognitive tasks. Moreover, the eIF4E/Fmr1 double mutant
      mice display increased levels of basal protein synthesis. The results of our
      study suggest that the eIF4E/Fmr1 double mutant mouse may be a reliable model to
      study cognitive dysfunction in the context of ASD. 

PMID- 26306461
TI  - Tribunal service was wrong in findings against orthopaedic registrar, say Appeal
      Court judges.

PMID- 26306462
TI  - Erratum to: Neuroprotective Effect of Hesperidin on Aluminium Chloride Induced
      Alzheimer's Disease in Wistar Rats.

PMID- 26306463
TI  - A novel synthesis of isoeugenol, [ring-(U)-(14)C].
AB  - A novel method for the preparation of isoeugenol, [ring-(U)-(14)C] is presented.
      Phenols and phenyl esters substituted in the para position with 1-hydroxyethyl or
      1-hydroxypropyl acetate esters when treated with 1,8-diazabicyclo[5.4.0]undec-7
      ene in dimethylformamide (DMF) eliminate the alkyl carboxylate function to give
      the unsaturated compound. The reaction fails with unsubstituted or ether
      substituted phenyl 1-hydroxyacetate esters.

PMID- 26306465
TI  - Molecular inhibitors of DNA repair: searching for the ultimate tumor killing
      weapon.
AB  - DNA repair (DR) inhibitors are small molecules that interact with DR proteins in
      order to disrupt their function and induce a 'strike' to the high fidelity of the
      mammalian DNA repair systems. Many anticancer therapies aim to harm the DNA of
      the usually highly proliferative cancer cell, causing it to undergo apoptosis. In
      response to this, cancer cells attempt to fix the induced lesion and reconstitute
      its genomic integrity, in turn reducing the efficacy of treatment. To overcome
      this, DR inhibitors suppress DNA repair proteins' function, increasing the
      potency and tumor killing effect of chemotherapy or radiotherapy. In this review,
      we discuss clinically applied novel inhibitors under translational investigation
      and we apply bioinformatic tools in order to identify repair proteins implicated
      in more than two phenomenically distinct DNA repair pathways (e.g., base excision
      repair and nonhomologous end joining), that is, the concept of 'synthetic
      lethality'. Our study can aid towards the optimization of this therapeutic
      strategy and, therefore, maximizing treatment effectiveness like in the case of
      radiation therapy. 

PMID- 26306464
TI  - The exosome controls alternative splicing by mediating the gene expression and
      assembly of the spliceosome complex.
AB  - The exosome is a complex with exoribonuclease activity that regulates RNA
      surveillance and turnover. The exosome also plays a role in regulating the
      degradation of precursor mRNAs to maintain the expression of splicing variants.
      In Neurospora, the silencing of rrp44, which encodes the catalytic subunit of the
      exosome, changed the expression of a set of spliceosomal snRNA, snRNP genes and
      SR protein related genes. The knockdown of rrp44 also affected the assembly of
      the spliceosome. RNA-seq analysis revealed a global change in bulk splicing
      events. Exosome-mediated splicing may regulate alternative splicing of NCU05290,
      NCU07421 and the circadian clock gene frequency (frq). The knockdown of rrp44 led
      to an increased ratio of splicing variants without intron 6 (I-6) and shorter
      protein isoform small FRQ (s-FRQ) as a consequence. These findings suggest that
      the exosome controls splicing events by regulating the degradation of precursor
      mRNAs and the gene expression, assembly and function of the spliceosome. 

PMID- 26306466
TI  - Resveratrol and anti-atherogenic effects.
AB  - The role of inflammation and oxidative stress in atherosclerosis development has
      been increasingly well recognized over the past decade. Inflammation has a
      significant role at all stages of atherosclerosis, including initiation,
      progression and plaque formation. Resveratrol is a naturally occurring
      polyphenolic compound found in grape products, berry fruits and red wine. Its
      ability to behave therapeutically as a component of red wine has attracted wide
      attention. Accumulating evidence suggests that it is a highly pleiotropic
      molecule that modulates numerous targets and molecular functions. Epidemiological
      studies indicate that the Mediterranean diet, rich in resveratrol, is associated
      with a reduced risk of atherosclerosis. Resveratrol is believed to decrease
      circulating low-density lipoprotein cholesterol levels, reduce cardiovascular
      disease risk; it reduces lipid peroxidation, platelet aggregation and oxidative
      stress. Resveratrol is considered a safe compound, since no significant toxic
      effects have been demonstrated after administration of a broad range of
      concentrations, and an effective anti-atherogenic agent. 

PMID- 26306467
TI  - Frameshift Mutations of CAB39L, an Activator of LKB1 Tumor Suppressor, in Gastric
      and Colorectal Cancers.

PMID- 26306468
TI  - Epidemiological, Clinicopathological and Virological Features of Merkel Cell
      Carcinomas in Medical Center of University of Pecs, Hungary (2007-2012).
AB  - Merkel cell carcinoma (MCC) is a rare, highly aggressive skin tumour. In 2008, a
      Merkel cell polyomavirus (MC) was identified in MCCs as a potential etiological
      factor of MCC. The aims of this retrospective study were to investigate the
      epidemiological, clinicopathological and virological features of MCCs. Between
      2007 and 2012, 11 patients had been diagnosed with MCC by histological methods in
      University of Pecs, Hungary. In eight MCC cases MC was tested by PCR (in primary
      skin lesions, lymph nodes/cutan metastases, MCC neighboring carcinomas).
      Clinicopathological characteristics (age, histological pattern, lymphovascular
      invasion, co-morbidities) of MC-positive and MC-negative cases were compared. MC
      was detected in three (37.5%) out of eight patients' primary tumour or
      metastasis. The average age was 73.8 (64.3 in MC-positive group). Except the
      youngest, 55 year-old patient (the primary tumour appeared on his leg), all
      tumours were found at the head and neck region. Immunosuppression (steroid
      therapy, chronic lymphoid leukaemia, chronic obstructive pulmonary disease)
      and/or old age were characteristic for all cases. Histological pattern was
      different in MC-positive and in MC-negative groups: MCCs with MC showed more
      homogeneous histological pattern, lack of lymphovascular invasion and were
      associated with better prognosis (mortality rate: 33% versus 80%). MCC associated
      with oncogenic virus is a newly recognized clinical entity. However, MC could not
      be detected in all histologically proven MCCs. The well-defined selection of
      patients/disease groups and better characterization of differences between MC
      positive and negative cases is an important step towards the recognition of the
      etiology and pathogenesis of all MCCs.

PMID- 26306470
TI  - An international surgical collaboration: humanitarian surgery in Brazil.
AB  - PURPOSE: Brazil is the fifth most populous country in the world with widespread
      regional and social inequalities. Regional disparities in healthcare are
      unacceptably large, with the remote and poor regions of the north and northeast
      having reduced life expectancy compared to the south region, where life
      expectancy approaches that of rich countries. We report our experience of a
      humanitarian surgery mission to the Amazonas state, in the northwest part of
      Brazil. METHODS: In August 2014, a team of seven consultant surgeons, and two
      trainees with the charity 'International Hernia', visited three hospitals in the
      Amazonas state to provide hernia surgery and training. RESULTS: Eighty-nine
      hernias were repaired in 74 patients (female = 22, male = 52) with a median age
      of 44 years (range 2-83 years). Nine patients underwent more than one type of
      hernia repair, and there were 9 laparoscopic inguinal and ventral incisional
      hernia repairs. Local doctors were trained in hernia repair techniques, and an
      International Hernia Symposium was held at the University of the State of
      Amazonas, Manaus. CONCLUSION: The humanitarian mission provided hernia surgery to
      an underserved population in Brazil and training to local doctors, building local
      sustainability. Continued cooperation between host and international surgeons for
      future missions to Brazil will ensure continuing surgical training and technical
      assistance.

PMID- 26306469
TI  - Endocytic pH regulates cell surface localization of glycolipid antigen loaded
      CD1d complexes.
AB  - Invariant natural killer T (iNKT) cells recognize glycolipid antigens presented
      by CD1d, an antigen presenting protein structurally similar to MHC class I.
      Stimulation of iNKT cells by glycolipid antigens can induce strong immune
      responses in vivo, with rapid production of a wide variety of cytokines including
      those classically associated with either T helper type 1 (Th1) or type 2 (Th2)
      responses. Alterations in the lipid tails or other portions of CD1d-presented
      glycolipid ligands can bias the iNKT response towards production of predominantly
      Th1 or Th2 associated cytokines. However, the mechanism accounting for this
      structure-activity relationship remains controversial. The Th1-biasing
      glycolipids have been found to consistently form complexes with CD1d that
      preferentially localize to plasma membrane cholesterol rich microdomains (lipid
      rafts), whereas CD1d complexes formed with Th2-biasing ligands are excluded from
      these microdomains. Here we show that neutralization of endosomal pH enhanced
      localization of CD1d complexes containing Th2-biasing glycolipids to plasma
      membrane lipid rafts of antigen presenting cells (APC). Transfer of APCs
      presenting these "stabilized" CD1d/alphaGC complexes into mice resulted in immune
      responses with a more prominent Th1-like bias, characterized by increased NK cell
      transactivation and interferon-gamma production. These findings support a model
      in which low endosomal pH controls stability and lipid raft localization of CD1d
      glycolipid complexes to regulate the outcome of iNKT cell mediated responses. 

PMID- 26306471
TI  - The dome procedure: a new technique for the reconstruction of the umbilicus.
AB  - PURPOSE: The absence of the umbilicus is, in essence, an aesthetic deformity of
      the abdominal wall. The goal of reconstructing the umbilicus is to obtain a
      natural, three-dimensional appearance. In this study, we present a new technique
      called the "dome procedure" for the reconstruction of the umbilicus. METHODS:
      This procedure can be applied under local anaesthesia on an outpatient basis and
      the drawing of the design is simple. The technique was applied to six patients
      who presented with an absence of the umbilicus following repair of a large
      incisional and umbilical hernia. RESULTS: No major or minor complications were
      encountered. Patient satisfaction was high after surgical intervention.
      CONCLUSIONS: The dome procedure, which enables the umbilicus to have a natural
      appearance with sufficient depression and normal-appearing wrinkles, is simple,
      easy to perform, and safe.

PMID- 26306473
TI  - Use of the Hammersmith Infant Neurological Examination in infants with cerebral
      palsy: a critical review of the literature.
AB  - The Hammersmith Infant Neurological Examination (HINE) has been proposed as one
      of the early neurological examination tools for the diagnosis of cerebral palsy
      (CP). The aim of the present study was to critically review the existing
      literature and our experience with the use of the HINE in infants at risk of CP.
      The published papers confirm that the HINE can play an important role in the
      diagnosis and prognosis of infants at risk of developing CP, and provide
      information on aspects of neurological findings impaired in different forms of CP
      and brain lesions. 

PMID- 26306472
TI  - Umbilical paracentesis for incarcerated umbilical hernia in patients with end
      stage liver disease.
AB  - PURPOSE: Patients with cirrhosis and ascites are prone to abdominal wall
      complications largely predominate by umbilical hernia. Elective surgery is
      indicated in select patients but a high morbidity and mortality rate occurs if it
      is performed in emergency conditions. METHODS: We present a clinical case of a
      patient with advanced alcoholic liver disease who came to the emergency room for
      an acutely incarcerated umbilical hernia. Due to the high surgical risk, we had
      to discuss other treatment options. RESULTS: The use of umbilical paracentesis
      for incarcerated hernia reduction in cirrhotic patients with tense ascites is a
      safe and reproducible technique. CONCLUSIONS: Umbilical paracentesis could be
      considered as an alternative to emergency surgery in these high-risk patients.

PMID- 26306474
TI  - Analyses of the modulatory effects of antibacterial silver doped calcium
      phosphate-based ceramic nano-powder on proliferation, survival, and angiogenic
      capacity of different mammalian cells in vitro.
AB  - In this study, the antibacterial, cytotoxic, and angiogenic activities of silver
      doped calcium phosphate-based inorganic powder (ABT or PAG) were systematically
      investigated. ABT powders containing varying silver content were fabricated using
      a wet chemical manufacturing method. Antibacterial efficiencies of the ABT
      powders were investigated using a standard test with indicator bacteria and
      yeast. The cytotoxic effects of ABT on three different fibroblast cells and human
      umbilical vein endothelial cells (HUVECs) were assessed using MTT assay. ABT
      powder exhibits concentration-related cytotoxicity characteristics. Apoptotic
      activity, attachment capability, and wound healing effects were examined on
      fibroblasts. The angiogenic activity of ABT was investigated by tube formation
      assay in HUVECs; 10 MUg ml(-1) and 100 MUg ml(-1) concentrations of the highest
      metal ion content of ABT did not disrupt the tube formation of HUVECs. All these
      tests showed that ABT does not compromise the survival of the cells and might
      impose regeneration ability to various cell types. These results indicate that
      silver doped calcium phosphate-based inorganic powder with an optimal silver
      content has good potential for developing new biomaterials for implant
      applications. 

PMID- 26306475
TI  - Dual-topology insertion of a dual-topology membrane protein.
AB  - Some membrane transporters are dual-topology dimers in which the subunits have
      inverted transmembrane topology. How a cell manages to generate equal populations
      of two opposite topologies from the same polypeptide chain remains unclear. For
      the dual-topology transporter EmrE, the evidence to date remains consistent with
      two extreme models. A post-translational model posits that topology remains
      malleable after synthesis and becomes fixed once the dimer forms. A second, co
      translational model, posits that the protein inserts in both topologies in equal
      proportions. Here we show that while there is at least some limited topological
      malleability, the co-translational model likely dominates under normal
      circumstances. 

PMID- 26306476
TI  - Long-Term Stability of Tramadol and Ketamine Solutions for Patient-Controlled
      Analgesia Delivery.
AB  - BACKGROUND: Subanesthetic doses of ketamine as an adjuvant to tramadol in patient
      controlled analgesia (PCA) for postoperative pain have been shown to improve the
      quality of analgesia. However, there are no such commercially available drug
      mixtures, and the stability of the combination has rarely been assessed. MATERIAL
      AND METHODS: Admixtures were assessed for periods of up to 14 days at 4 degrees C
      and 25 degrees C. Three different mixtures of tramadol and ketamine (tramadol 5.0
      mg/mL + ketamine 0.5 mg/mL, tramadol 5.0 mg/mL + ketamine 1.0 mg/mL, and tramadol
      5.0 mg/mL + ketamine 2.0 mg/mL) were prepared in polyolefin bags by combining
      these 2 drugs with 0.9% sodium chloride (normal saline [NS]). The chemical
      stability of the admixtures was evaluated by a validated high-performance liquid
      chromatography (HPLC) method and by measurement of pH values. Solution appearance
      and color were assessed by observing the samples against black and white
      backgrounds. Solutions were considered stable if they maintained 90% of the
      initial concentration of each drug. RESULTS: The percentages of initial
      concentration of tramadol and ketamine in the various solutions remained above
      98% when stored at 4 degrees C or 25 degrees C over the testing period. No
      changes in color or turbidity were observed in any of the prepared solutions.
      Throughout this period, pH values remained stable. CONCLUSIONS: The results
      indicate that the drug mixtures of tramadol with ketamine in NS for PCA delivery
      systems were stable for 14 days when stored in polyolefin bags at 4 degrees C or
      25 degrees C.

PMID- 26306477
TI  - Giant maxillary hemangioma in a child--Ketamine to the rescue.

PMID- 26306478
TI  - [Falling from a height: Psychiatric comorbidity and complications].
AB  - OBJECTIVE: To investigate whether a mental disorder increases the occurrence of
      complications in patients after 'a fall from a height'. DESIGN: Retrospective
      descriptive study. METHODS: Data on all patients admitted following a 'fall from
      a height' in the period 2004-2012 was retrieved from the trauma registry of the
      Academic Medical Center (AMC) in Amsterdam, the Netherlands. This was combined
      with data from the National Surgical Complications Registry (LHCR). A chart
      review was conducted to determine the presence of mental disorders in these
      patients. Corrected risk ratio for the risk of complications in patients with a
      psychological disorder was calculated using the Mantel-Haenszel method. RESULTS:
      A total of 507 patients presented to the emergency department at the AMC
      following a fall from a height; 147 patients (29%) experienced 1 or more
      complications and 131 patients (25.8%) had a mental disorder. Complications arose
      in 60 patients with a mental disorder (45.8%) and in 87 patients (23.1%) without
      a mental disorder. The corrected risk ratio showed that a mental disorder is a
      statistically significant independent predictor of complications (risk ratio:
      1.58; 95% confidence interval: 1.21-2.06). CONCLUSION: The risk of complications
      following a fall from a height in patients with a mental disorder is one and a
      half times higher than in patients without a mental disorder. This mental
      disorder is a significant independent predictor of a medical complication
      following a fall from a height.

PMID- 26306479
TI  - [The future of hyperbaric oxygen therapy: added value in the treatment of late
      radiation injury?].
AB  - There is some evidence for the benefit of hyperbaric oxygen therapy in late
      radiation tissue injury (LRTI) affecting the head, neck and lower bowel, but
      there is little evidence for or against the benefit in other tissues (e.g. the
      breast) affected by LRTI. There is a need for large prospective trials including
      quality-of-life and cost-effectiveness studies, because hyperbaric oxygen therapy
      is becoming more popular. 

PMID- 26306480
TI  - [Enophthalmos as a first sign of breast cancer].
AB  - BACKGROUND: Metastasis of breast carcinoma to the orbit is characterized by
      symptoms of altered appearance and double vision. A combination of enophthalmos,
      ptosis and impairment of eye movements is typical. Sometimes these symptoms are
      the first manifestation of breast carcinoma. CASE DESCRIPTION: Two female
      patients, aged 66 and 52, presented with enophthalmos. Both had recently
      undergone mammography with no abnormalities being observed. CT scans of these
      patients disclosed an intra-orbital, space-occupying process. Histological
      examination of biopsies from the abnormal tissue revealed that both patients had
      metastatic breast carcinoma. CONCLUSION: In a female patient with non-traumatic
      enophthalmos, metastasis of breast carcinoma must be ruled out and reliance may
      not be placed on a mammogram revealing no abnormalities.

PMID- 26306481
TI  - [A newborn with an abnormal position of both legs].
AB  - A baby was born with an abnormal position of both legs due to congenital genu
      recurvatum. This is a rare condition which can appear as an isolated deformity,
      but is also associated with other musculoskeletal anomalies and syndromes. The
      prognosis is generally good. 

PMID- 26306482
TI  - [Impending caecal blowout due to endometriosis].
AB  - BACKGROUND: Endometrial tissue is present outside the uterine cavity in 6-10% of
      fertile women. Associated symptoms such as dysmenorrhoea, dyspareunia and
      abdominal discomfort are non-specific. For this reason, endometriosis is not
      always considered in women with abdominal symptoms. Endometriosis can also
      manifest itself as an acute surgical emergency such as an intestinal obstruction.
      CASE DESCRIPTION: A 29-year-old woman was admitted to our hospital with acute
      lower abdominal pain and vomiting. On rectal examination a firm mass was
      palpable. CT scan of the abdomen showed the loops of colon to be extremely
      dilated. As a caecal blowout seemed imminent we carried out a laparotomy which
      revealed an obstruction of the rectum caused by severe endometriosis. CONCLUSION:
      In fertile women presenting with signs of acute bowel obstruction, endometriosis
      should be included in the differential diagnosis and an early gynaecological
      consultation is indicated.

PMID- 26306483
TI  - [A homeless, uninsured illegal alien suffering from psychosis and multiple
      fractures: providing efficient care to such patients].
AB  - We present the case of a 37-year-old psychotic, homeless man from Albania, who
      sustained multiple fractures after jumping from a third-floor window. The patient
      was uninsured and did not consent to transfer to a hospital in Albania because of
      paranoid delusions. Eventually he was hospitalised for nearly 30 weeks in
      hospital and a nursing home. Various factors of this complex case are considered,
      such as the co-morbidity of somatic and psychiatric symptoms, the absence of
      family support and the financial regulations that apply to uninsured patients.
      Doctors who are presented with similar complex cases are advised to organise
      frequent multidisciplinary evaluations with all health care workers involved. We
      encourage searching for creative interventions which serve both the best
      interests of the individual patient, and - where possible - also minimize the
      total cost of health care to society. 

PMID- 26306484
TI  - [Electronic cigarettes: use, health risks, and effectiveness as a cessation
      method].
AB  - The use of electronic cigarettes (e-cigarettes) among adults in the Netherlands
      is increasing but is still relatively low. Increasing numbers of young people
      abroad are experimenting with e-cigarettes but no trend data for the Netherlands
      are available to date. Young people who experiment with e-cigarettes are
      principally those young people who already smoke conventional cigarettes or have
      done so in the past; the same applies to adults. There are no indications that
      experimenting with e-cigarettes can lead to tobacco addiction. Although the
      vapour from e-cigarettes contains substances that are harmful to health, the
      health risks from the use of e-cigarettes are far smaller than those from smoking
      conventional cigarettes. Too few research data are available to be able to
      conclude that e-cigarettes are an effective aid to smoking cessation.

PMID- 26306485
TI  - [Nephrotic syndrome in Crohn's disease].
AB  - BACKGROUND: The differential diagnosis of nephrotic syndrome is diverse. Systemic
      conditions and medication such as NSAIDs can cause this syndrome. CASE
      DESCRIPTION: A 33-year-old male with Crohn's disease for which he was receiving
      adalimumab noticed he was gaining weight and had swollen ankles. Examination
      revealed nephrotic syndrome without renal insufficiency. Renal biopsy showed a
      membranous glomerulopathy. We excluded secondary causes of membranous
      glomerulopathy such as diabetes mellitus, systemic lupus erythematosus, viral
      infection or malignancy. We treated the patient with high-dose glucocorticoids on
      a weaning schedule and adalimumab was discontinued. This regimen resulted in
      complete remission. It is likely that the nephrotic syndrome with membranous
      glomerulopathy was associated with adalimumab. CONCLUSION: In patients with
      nephrotic syndrome based on membranous glomerulopathy both primary and secondary
      causes, such as use of medication, need to be excluded.

PMID- 26306486
TI  - [Palliative care for a homeless person].
AB  - Homeless people have substantial health disadvantages as compared to the general
      population, and excessive losses in life expectancy. High proportions of
      psychiatric disorders, substance abuse and intellectual disability have been
      reported. This makes palliative care for this population extremely complex. A 55
      year-old man, addicted to heroin and cocaine, was diagnosed with metastatic lung
      cancer. His terminal phase of life was complicated by many admissions to
      different care settings and problems with symptom management. Involvement of a
      palliative care consultation team and transfer to a homeless shelter, to which
      homeless people with life-threatening diseases could be admitted, gave both the
      patient and his family relief. This case illustrates that palliative care in
      homeless patients may be extremely complex due to the specific physical and
      psychosocial features involved. Such care should be offered proactively and on a
      multidisciplinary basis. 

PMID- 26306487
TI  - [David Sackett and 25 years of evidence-based medicine: person and the context].
AB  - David Sackett, the father of evidence-based medicine (EBM), died recently -
      exactly 25 years after the term EBM was coined. This coincidence calls for
      reflection on the historical significance of EBM and on Sackett's role. The rise
      of EBM appears to be part of a much broader development: a shift from 'trust in
      the experts' to 'trust in numbers' that occurred under the pressures of the socio
      political conditions of the late twentieth century. Insight into this historical
      context contributes to a better understanding of the emergence, merits and
      weaknesses of EBM and of the current tensions between medical professionals and
      insurers. However, context alone does not explain everything; the course of
      history - and the history of EBM - is partly determined by special men and women,
      individual reformers who manage to set things and people in motion. David Sackett
      is an excellent example of this. 

PMID- 26306488
TI  - [What are the health benefits of the most expensive healthcare system in
      Europe?].
AB  - Since the year 2000, healthcare expenditure in the Netherlands has seen a
      meteoric rise and as a result the Netherlands now has the highest level of
      healthcare expenditure (expressed as a percentage of national income) of all
      European countries. Whether this has led to better population health outcomes is,
      however, unclear. The only outcome for which there is some evidence is life
      expectancy at birth, which has probably improved as a result of more and better
      healthcare. Unfortunately, despite very high levels of healthcare spending,
      current Dutch life expectancy is not among the best in Europe, partly because of
      a relatively high prevalence of smoking and insufficient tobacco control
      measures. More health gains could have been achieved if greater priority had been
      given to prevention. 

PMID- 26306489
TI  - [More complications after a fall from height in patients with a mental disorder].
AB  - In this issue of the Nederlands Tijdschrift voor Geneeskunde researchers from the
      Amsterdam Medical Centre describe the coincidence of psychiatric comorbidities
      and complications in patients suffering from a fall from height. Apart from
      typical somatic issues related to these diseases, such as substance abuse and
      specific medication, the attitude of healthcare workers toward this category of
      patients is discussed and critically appraised. 

PMID- 26306490
TI  - Association between feeding practices and weight status in young children.
AB  - BACKGROUND: Inappropriate feeding practices during infancy may lead to
      overweight. The aims of this study are to investigate the growth of children in
      the first 18 months of life; to evaluate the feeding practices of caregivers
      using developed Young Child Feeding Questionnaire; and to investigate caregivers'
      feeding attitudes and behaviors associated with infants' weight status. METHODS:
      Six month-old infants and their main caregivers entering the Kongjiang Community
      Health Center for a routine well-child check were recruited for this study and
      followed up every 6 months for 12 months. Questionnaire survey was carried out
      through on-site face-to-face interview at each visit with the main caregivers of
      children using Young Child Feeding Questionnaire, which included caregivers'
      feeding attitudes and behaviors. The weight and length of children were measured
      at each visit. RESULTS: Among 197 children who completed the investigation at 18
      months of age, 64 (32.49%) children were overweight (BMI-for-age z scores > +1).
      The increases in weight-for-age z scores and BMI-for-age z scores from birth to 6
      months, 12 to 18 months and birth to 18 months in overweight children were
      significantly higher than those in normal weight children (P < 0.001). In normal
      weight children, caregivers worried more about children's being "underweight" and
      "eating less" (P = 0.001), whereas caregivers with overweight children worried
      more about children's "eating too much" and being "overweight" (P < 0.001). In 64
      overweight infants, the scores of "concern about child's food intake" were
      significantly correlated with increase in BAZ between 12 and 18 months (Bata =
      0.293, P = 0.029). CONCLUSIONS: Young Child Feeding Questionnaire is a valid tool
      for evaluating feeding practice of caregivers. The rapid BMI gain in overweight
      children may be associated with some inappropriate feeding attitudes and
      behaviors of caregivers.

PMID- 26306492
TI  - Essential role of endocytosis for interleukin-4-receptor-mediated JAK/STAT
      signalling.
AB  - Many important signalling cascades operate through specialized signalling
      endosomes, but a corresponding mechanism has as yet not been described for
      hematopoietic cytokine receptors. Based on live-cell affinity measurements, we
      recently proposed that ligand-induced interleukin-4 receptor (IL-4R) complex
      formation and thus JAK/STAT pathway activation requires a local subcellular
      increase in receptor density. Here, we show that this concentration step is
      provided by the internalization of IL-4R subunits through a constitutive, Rac1-,
      Pak- and actin-mediated endocytosis route that causes IL-4R subunits to become
      enriched by about two orders of magnitude within a population of cortical
      endosomes. Consistently, ligand-induced receptor dimers are preferentially
      detected within these endosomes. IL-4 signalling can be blocked by
      pharmacological inhibitors targeting the actin polymerization machinery driving
      receptor internalization, placing endocytosis unambigously upstream of receptor
      activation. Taken together, these observations demonstrate a role for endocytosis
      that is mechanistically distinct from the scaffolding function of signalling
      endosomes in other pathways. 

PMID- 26306491
TI  - Plectin as a prognostic marker in non-metastatic oral squamous cell carcinoma.
AB  - BACKGROUND: Oral squamous cell carcinoma (OSCC) is associated with a poor 5-year
      survival rate. In general, patients diagnosed with small tumors have a fairly
      good prognosis, but some small tumors have an aggressive behavior leading to
      early death. There are at present no reliable prognostic biomarkers for oral
      cancers. Thus, to optimize treatment for the individual patient, there is a need
      for biomarkers that can predict tumor behavior. METHOD: In the present study the
      potential prognostic value of plectin was evaluated by a tissue microarray (TMA)
      based immunohistochemical analysis of primary tumor tissue obtained from a North
      Norwegian cohort of 115 patients diagnosed with OSCC. The expression of plectin
      was compared with clinicopathological variables and 5 year survival. RESULTS: The
      statistical analysis revealed that low expression of plectin in the tumor cells
      predicted a favorable outcome for patients with non-metastatic disease (p =
      0.008). Furthermore, the expression of plectin was found to correlate (p = 0.01)
      with the expression of uPAR, which we have previously found to be a potential
      prognostic marker for T1N0 tumors. CONCLUSIONS: Our results indicate that low
      expression of plectin predicts a favorable outcome for patients with non
      metastatic OSCC and the expression level of plectin may therefore be used in the
      treatment stratification for patients with early stage disease.

PMID- 26306493
TI  - ICA1L forms BAR-domain complexes with PICK1 and is crucial for acrosome formation
      in spermiogenesis.
AB  - Mutations in the Pick1 gene cause globozoospermia, a male infertility disorder,
      in both mice and humans. PICK1 is crucial for vesicle trafficking, and its
      deficiency in sperm cells leads to abnormal vesicle trafficking from the Golgi to
      the acrosome. This eventually disrupts acrosome formation and leads to male
      infertility. Here, we identified ICA1L, which has sequence similarities to ICA69
      (also known as ICA1), as a new BAR-domain binding partner of PICK1. ICA1L is
      expressed in testes and brain, and is the major binding partner for PICK1 in
      testes. ICA1L and PICK1 are highly expressed in spermatids and trafficked
      together at different stages of spermiogenesis. ICA1L-knockout mice were
      generated by CRISPR-Cas technology. PICK1 expression was reduced by 80% in the
      testes of male mice lacking ICA1L. Sperm from ICA1L-knockout mice had
      abnormalities in the acrosome, nucleus and mitochondrial sheath formation. Both
      total and mobile sperm numbers were reduced, and about half of the remaining
      sperm had the characteristics of globozoospermia. These defects ultimately
      resulted in reduced fertility of male ICA1L-knockout mice, and ICA69/ICA1L-double
      knockout male mice were sterile. 

PMID- 26306494
TI  - Basement Membrane-Based Glucose Sensor Coatings Enhance Continuous Glucose
      Monitoring in Vivo.
AB  - BACKGROUND: Implantable glucose sensors demonstrate a rapid decline in function
      that is likely due to biofouling of the sensor. Previous efforts directed at
      overcoming this issue has generally focused on the use of synthetic polymer
      coatings, with little apparent effect in vivo, clearly a novel approach is
      required. We believe that the key to extending sensor life span in vivo is the
      development of biocompatible basement membrane (BM) based bio-hydrogels as
      coatings for glucose sensors. METHOD: BM based bio-hydrogel sensor coatings were
      developed using purified BM preparations (ie, Cultrex from Trevigen Inc).
      Modified Abbott sensors were coated with Cultrex BM extracts. Sensor performance
      was evaluated for the impact of these coatings in vitro and in vivo in a
      continuous glucose monitoring (CGM) mouse model. In vivo sensor function was
      assessed over a 28-day time period expressed as mean absolute relative difference
      (MARD) values. Tissue reactivity of both Cultrex coated and uncoated glucose
      sensors was evaluated at 7, 14, 21 and 28 days post-sensor implantation with
      standard histological techniques. RESULTS: The data demonstrate that Cultrex
      based sensor coatings had no effect on glucose sensor function in vitro. In vivo
      glucose sensor performance was enhanced following BM coating as determined by
      MARD analysis, particularly in weeks 2 and 3. In vivo studies also demonstrated
      that Cultrex coatings significantly decreased sensor-induced tissue reactions at
      the sensor implantation sites. CONCLUSION: Basement-membrane-based sensor
      coatings enhance glucose sensor function in vivo, by minimizing or preventing
      sensor-induced tissues reactions.

PMID- 26306495
TI  - Foreign Body Reaction to Implantable Biosensors: Effects of Tissue Trauma and
      Implant Size.
AB  - BACKGROUND: Implantable biosensors for continuous glucose monitoring can greatly
      improve diabetes management. However, their applications are still associated
      with some challenges and one of these is the gradual functionality loss
      postimplantation as a consequence of the foreign body response (FBR). Sensor
      miniaturization in combination with drug-eluting biocompatible coatings is a
      promising strategy to enhance in vivo performance. However, limited study has
      been performed to understand the effect of initial trauma and implant size on
      foreign body reaction as well as in vivo performance of implantable glucose
      sensors. METHODS: Different initial trauma was induced by implanting composite
      coated dummy sensors into rats using various sized needles and 3 different-sized
      dummy sensors were implanted to examine the size effect. Histological evaluation
      was performed to relate the inflammatory cell counts and foreign body capsule
      thickness with the implantation needle size and sensor size respectively. The
      effect of biocompatible coating on the performance of implantable glucose sensors
      was determined using both coated amperometric glucose sensors and microdialysis
      probes. RESULTS: The results revealed that the degree of acute inflammation was
      mainly controlled by the extent of the initial trauma: the greater the trauma,
      the greater the acute inflammatory response. Implant size did not affect the
      acute inflammatory phase. However, the extent of chronic inflammation and fibrous
      encapsulation were affected by sensor size: the smaller the size the less the
      extent of chronic inflammation and fibrous encapsulation. Glucose sensors
      implanted using 14 gauge needles showed significantly lower initial in vivo
      response compared to those implanted using 16 gauge needles. This was not
      observed for sensors with dexamethasone-eluting biocompatible coatings since
      inflammation was suppressed. CONCLUSIONS: The results of the current study
      indicate that the extent of the inflammatory response post-sensor implantation
      varies as a function of the initial tissue trauma as well as the sensor size.
      Accordingly, miniaturization of implantable biosensors together with the
      utilization of a drug-eluting biocompatible composite coating may be a promising
      strategy to achieve long-term reliable continuous glucose monitoring.

PMID- 26306496
TI  - Clinical phenotype classification for selective immunoglobulin A deficiency.
AB  - Selective immunoglobulin A deficiency (SIgAD) is the most common predominantly
      antibody deficiency, with a wide range of presentations from asymptomatic to
      severe manifestations. Although many studies have investigated different aspects
      of SIgAD, no study has yet presented a comprehensive classification of this
      disease. Based on clinical manifestation of patients and various immune
      abnormalities associated with SIgAD, this group of patients could be classified
      into five different phenotypes including asymptomatic, minor infectious,
      allergic, autoimmune and severe phenotypes. This classification aids physicians
      in identifying patients and in choosing appropriate management and treatment as
      well as homogenized groups for molecular and genetic studies. 

PMID- 26306497
TI  - Regulatory B cells mediate tolerance to apoptotic self in health: implications
      for disease.
AB  - B cells are able to regulate immune responses through the secretion of IL-10 and
      other inhibitory cytokines, though no transcription factor that can define
      'regulatory B cells' as a separate lineage has yet been found. Instead it is
      likely that this function arises as a result of the immune context in which B
      cells find themselves and the stimuli they perceive. However, some B cells found
      within the B1a and the marginal zone subsets have a greater propensity to produce
      IL-10 than others. What are the natural stimuli for these cells to induce immune
      regulation? We discuss the role that the recognition of autoantigens exposed by
      apoptotic cells plays in stimulating IL-10 production in mouse and human studies.
      This mechanism involves the recognition and uptake of self-antigens by
      autoreactive BCRs, for delivery to endocytic compartments, where apoptosis
      derived DNA binds to TLR9, driving IL-10 production. These 'natural' regulatory B
      cells represent a way of maintaining tolerance to self. We discuss how this may
      operate in inflammatory lesions where there is an excess of apoptotic leukocytes
      and how this impacts on our understanding of autoimmune disease. 

PMID- 26306499
TI  - The forgotten risk? A systematic review of the effect of reminder systems for
      postpartum screening for type 2 diabetes in women with previous gestational
      diabetes.
AB  - BACKGROUND: Screening for type 2 diabetes is recommended for women with previous
      gestational diabetes (GDM). However, the screening rates remain low. We aimed to
      evaluate the reminders and reminder systems for women with previous GDM and the
      health professionals in primary and secondary health care with screening rate
      among postpartum women as primary outcome. METHODS: Observational and
      intervention studies were included and the PRISMA guidelines were followed for
      the literature extraction. RESULTS: Six studies were included: two long-term
      follow up studies and four early terms. Five studies focused on secondary care
      settings and one on primary care. Three studies focused on reminders to
      postpartum women only, two studies to both the women and health care
      professional, and one study on the health care provider only. Types of reminders
      varied from letters, emails, and personal telephone calls to the women to
      register-based reminders or letters to the health care professionals. Reminders
      were efficient but efficiency varied between studies. Two studies found that
      direct telephone calls strengthened the reminding of the women. The effect of
      reminding both the women and the health professional screening rates decreased
      compared to reminding either health professionals or reminding the women
      separately. CONCLUSIONS: Reminders have a potential for early detection and
      prevention of type 2 diabetes in this high risk group of women; however, the kind
      of reminder and the frequency of reminders should be carefully considered
      accordingly to the target group.

PMID- 26306500
TI  - How to improve the equity of health financial sources? - Simulation and analysis
      of total health expenditure of one Chinese province on system dynamics.
AB  - INTRODUCTION: We simulate and analyze Total Health Expenditure (THE) in financial
      sources and other economic indicators (such as THE per capita, GDP, etc.) in a
      province of China from 2002 to 2012 on System Dynamics. METHODS: Based on actual
      data and certain mathematical methods, we use system dynamic software to
      construct a logic model for THE and changing proportions, and thus simulate the
      actual conditions of development and changes in THE. RESULTS: According to the
      simulation results, the government possess the largest investment in the average
      annual growth rate of THE, which was 25.16% in 2012. Social investment comprises
      the majority of the possession ratio, which was up to 41.20%. CONCLUSIONS: The
      personal investment growth rate decreased by almost 21%, but the total amount of
      personal investment increased by 28075 million yuan, which is far higher than the
      increase in government investment. Individuals are still the main carriers of
      health care expenses. The equity of health financial sources is still poor. The
      System Dynamics method used in this paper identifies a dynamic measurement
      process, provides a scientific basis for simulation and analysis of the changes
      in THE and its key constraining factors, as well as put forward suggestions for
      the improvement of equity of health financial sources.

PMID- 26306498
TI  - Group 2 innate lymphoid cells in disease.
AB  - Group 2 innate lymphoid cells (ILC2) are now recognized as an important innate
      source of type-2 effector cytokines. Although initially associated with mucosal
      tissues, it is clear that ILC2 are present in diverse anatomical locations. The
      function of ILC2 at these sites is equally varied, and although ILC2 represent a
      relatively minor population, they are fundamentally important regulators of
      innate and adaptive immune processes. As such, there is much interest to
      understand the role of ILC2 in diseases with a type-2 inflammatory component.
      This review explores the known roles of ILC2 in disease, and the diseases that
      show associations or other strong evidence for the involvement of ILC2. 

PMID- 26306501
TI  - Ultralong In2S3 Nanotubes on Graphene Substrate with Enhanced Electrocatalytic
      Activity.
AB  - Ultralong one-dimensional (1D) nanostructures including nanowires or nanotubes
      have been extensively studied because of their widespread applications in many
      fields. Although a lot of methods have been reported to prepare In2S3 nanotubes,
      approaching these nanotubes through one-pot solution synthesis is still extremely
      difficult, probably because of the intrinsic isotropic crystal growth
      characteristic of In2S3. In this article, we demonstrated a self-assembly
      approach for hydrothermal synthesis of In2S3 nanotubes/graphene composites, which
      contain ultralong (up to 10 MUm) In2S3 nanotubes on graphene substrate. The
      influence of several important synthetic parameters on the final products has
      been systematically investigated. Importantly, the as-prepared In2S3
      nanotubes/graphene composites can be easily cast on FTO to form a film, which can
      be used as a counter electrode. Our research indicates that the as-fabricated
      counter electrode exhibits excellent electrocatalytic activity toward the iodide
      species (I-/I3-) reduction reaction and very high energy conversion efficiency
      (8.01%) in dye-sensitized solar cells.

PMID- 26306502
TI  - Patients' perceptions of physical activity before and after joint replacement: a
      systematic review with meta-ethnographic analysis.
AB  - BACKGROUND: It has been perceived that people following total hip arthroplasty
      (THA) or total knee arthroplasty (TKA) have the capability, with reduced pain, to
      increase their levels of physical activity. OBJECTIVES: To determine the
      attitudes and perceptions of people awaiting or having undergone THA or TKA to
      physical activity post-arthroplasty and to identify potential facilitators or
      barriers to engage in active living and physical activity pursuits. METHODS:
      Systematic review of published and unpublished databases was undertaken from
      their inception to November 2014. Studies exploring the attitudes and perceptions
      of people awaiting or having undergone THA or TKA to physical activity post
      arthroplasty were included. Data were analysed through a meta-ethnography
      approach. RESULTS: From 528 citations, 13 papers were eligible, sampling 282
      people post-THA or TKA. The literature was judged moderate to high quality.
      Following THA and TKA, people either wished to return to their pre-pathology
      level of physical activity or simply be able to engage in less physically
      demanding activities that are meaningful to them and their lifestyles. Barriers
      to engaging in higher levels of physical activity were largely related to limited
      information, which culminated in fear surrounding 'doing the right thing' both
      for individual's recovery and the longevity of the joint replacement.
      CONCLUSIONS: While many people post-THA or TKA wish to return to pre-pathological
      physical activity status, there is limited interest in actually undertaking
      greater levels of physical activity post-arthroplasty either for pleasure or
      health gains. Improvement in education and awareness of this may be key drivers
      to improve habitualisation of physical activity post-arthroplasty. TRIAL
      REGISTRATION NUMBER: CRD42014014995.

PMID- 26306503
TI  - Honorary authorship in postgraduate medical training.
AB  - OBJECTIVES: To determine whether postgraduate medical trainees are exposed to
      honorary authorship, whether they are aware of the topic and if they believe that
      further support and education concerning this issue is needed. METHODS:
      Postgraduate medical trainees were contacted by email with a link to our
      questionnaire on two occasions (2 and 26 February 2014) and then contacted in
      person (June-November 2014). The questionnaire topics included demographics,
      authorship practice beliefs and experience, and authorship policy-related
      questions. We also determined the proportion of perceived, International
      Committee of Medical Journal Editors (ICMJE)-defined and unperceived honorary
      authorship in the respondent group. RESULTS: The response rate was 27.7%. The
      prevalence of perceived, ICMJE-defined and unperceived honorary authorship was
      38.1%, 57.3% and 24.2%, respectively; 90.1% were unaware of the ICMJE authorship
      criteria, 92.6% were unaware of a support system for authorship disputes, but
      91.8% believed such a system should be implemented and 93.3% believed medical
      trainees and faculty should be instructed on authorship guidelines. CONCLUSIONS:
      A paradigm shift from the current system is needed, where enforcement of ethical
      authorship practices is shifted away from journal editors. Instruction on the
      topic should be provided to medical trainees throughout medical school and
      continued during further training. A process should also be outlined to resolve
      authorship disputes. These measures may encourage researchers to have an open
      discussion on the topic prior to the commencement of a research project, and to
      resolve authorship conflicts in a constructive manner. We also hope this paper
      encourages further work on the topic.

PMID- 26306504
TI  - Thermography: a technique for assessing the risk of developing diabetic foot
      disorders.

PMID- 26306505
TI  - Attenuating Diabetes: What Really Works?
AB  - Diabetes mellitus is characterized by loss of glucose homeostasis; altered
      metabolism of glucose, proteins and lipids. Although a number of effective
      allopathic medicines are currently available for treatment and management of
      diabetes, but prevalence of side effects and higher cost poses a big challenge to
      the goal of pharmacotherapy. Herbs are mine of medicinal agents that are found to
      be efficacious, cost effective and safe in preventing diabetes and a number of
      plants have been used in management or treatment of diabetes. Modern
      pharmacopoeia has a healthy number of plant derived medicines and a large number
      of medicines from allopathic system are derived from the plant sources. This
      review aims to assess currently available preclinical and clinical knowledge of
      medicinal herbs intended for the management of diabetes and their mode of action.

PMID- 26306507
TI  - The Satisfaction and Use of Research Ethics Board Information Systems in Canada.
AB  - This article reports findings from a national survey of Research Ethics Board
      (REB) personnel across Canada on the satisfaction and use of information systems
      that support the review and administration of research ethics protocols. Findings
      indicate that though a wide variety of REB systems are utilized, the majority
      fall short of desired characteristics. Despite these shortcomings, most
      respondents are satisfied with their current REB systems. Satisfaction is
      dependent on the volume of protocols processed in relation to the robustness of
      the system. Boards with higher volumes are more satisfied with full-fledged
      systems; however, the satisfaction of REBs with lower volumes is not affected by
      the robustness of the REB system used. Recommendations are provided. 

PMID- 26306508
TI  - An Evaluation of Research Ethics in Undergraduate Health Science Research
      Methodology Programs at a South African University.
AB  - The amended research ethics policy at a South African University required the
      ethics review of undergraduate research projects, prompting the need to explore
      the content and teaching approach of research ethics education in health science
      undergraduate programs. Two qualitative data collection strategies were used:
      document analysis (syllabi and study guides) and semi-structured interviews with
      research methodology coordinators. Five main themes emerged: (a) timing of
      research ethics courses, (b) research ethics course content, (c) sub-optimal use
      of creative classroom activities to facilitate research ethics lectures, (d)
      understanding the need for undergraduate project research ethics review, and (e)
      research ethics capacity training for research methodology lecturers and
      undergraduate project supervisors. 

PMID- 26306506
TI  - 18-Fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography scan
      for monitoring the therapeutic response in experimental Staphylococcus aureus
      foreign-body osteomyelitis.
AB  - BACKGROUND: 18-Fluoro-2-deoxy-D-glucose positron emission tomography combined
      with computed tomography ((18)F-FDG PET/CT) scan is useful for diagnosis of
      osteoarticular infections. Whether (18)F-FDG PET/CT scanning may be used for
      therapeutic monitoring is not clear. The objective of this study was to develop
      (18)F-FDG PET/CT scanning for monitoring therapeutic response to antimicrobials
      in experimental Staphylococcus aureus osteomyelitis. METHODS: A total of 22
      rabbits were studied. In 20 animals, the right tibia was inoculated
      intraoperatively with S. aureus. Two control animals were inoculated with normal
      saline. A needle was placed in the tibia as a foreign body. Infection was allowed
      to develop for 21 days when (18)F-FDG PET/CT was performed, the needle was
      removed, and bone specimens were cultured to confirm infection. Antimicrobial
      therapy with daptomycin was initiated in all successfully infected animals for 1,
      3, or 6 weeks. Following completion of treatment, a second (18)F-FDG PET/CT was
      performed, animals were euthanized, and infected tibias were harvested for
      quantitative cultures and histology. A positive scan was defined as (18)F-FDG
      signal activity greater in the infected tibia than that of the contralateral non
      infected control tibia. Therapeutic response was measured by the change of (18)F
      FDG signal activity in the infected tibia. RESULTS: All successfully infected
      animals (n = 14), with microbiologically and/or histologically confirmed
      osteomyelitis, had positive (18)F-FDG PET/CT scans, while the two control animals
      had negative scans despite the presence of the foreign body [mean maximum
      standardized uptake value (SUVmax) (+/-SD) values 2.96 (+/-0.80) vs. 1 (+/-1.10),
      respectively, P = 0.04]. In the 14 successfully infected animals, the mean SUVmax
      was significantly higher in the infected compared to the uninfected tibia (P <
      0.0001). A SUVmax of 1.4, when used as a cutoff for infection, yielded a
      diagnostic accuracy of 93 %. At the end of treatment, successfully treated
      animals and saline controls had a negative (18)F-FDG PET/CT scan (n = 4), while
      animals with persistent infection despite treatment (n = 12) had a positive (18)F
      FDG PET/CT scan (SUVmax 1.0-3.0) (p < 0.001). SUVmax values were significantly
      reduced after 42 days of treatment from 3.15 +/- 0.5 (day 7) to 1.71 +/- 0.37
      (day 42) (p = 0.05). CONCLUSIONS: (18)F-FDG PET/CT scan is a sensitive and
      specific tool in therapeutic monitoring of experimental foreign-body
      osteomyelitis.

PMID- 26306509
TI  - Risk and Representation in Research Ethics: The NunatuKavut Experience.
AB  - This article examines Canadian policy governing the ethics of research involving
      Indigenous communities. Academics and community members collaborated in research
      to examine how best to apply the Tri-Council Policy Statement guidelines in a
      community with complex and multiple political and cultural jurisdictions. We
      examined issues of NunatuKavut (Southern Inuit) authority and representation in
      relation to governance of research in a context where community identity is
      complex and shifting, and new provincial legislation mandates centralized ethics
      review. We describe the politics of risk--the ways in which collective identity
      and research risks are co-constructed. Our case study illustrates that collective
      consent to research must emphasize shifting identity construction in relation to
      the particular risks and benefits invoked by the research question, to ascertain
      with which groups or individuals the negotiation of risk should take place in the
      first place. We conclude by describing a necessary re-imagining of policy
      governing research ethics involving Indigenous communities.

PMID- 26306510
TI  - Genomic analysis of codon usage shows influence of mutation pressure, natural
      selection, and host features on Marburg virus evolution.
AB  - BACKGROUND: The Marburg virus (MARV) has a negative-sense single-stranded RNA
      genome, belongs to the family Filoviridae, and is responsible for several
      outbreaks of highly fatal hemorrhagic fever. Codon usage patterns of viruses
      reflect a series of evolutionary changes that enable viruses to shape their
      survival rates and fitness toward the external environment and, most importantly,
      their hosts. To understand the evolution of MARV at the codon level, we report a
      comprehensive analysis of synonymous codon usage patterns in MARV genomes.
      Multiple codon analysis approaches and statistical methods were performed to
      determine overall codon usage patterns, biases in codon usage, and influence of
      various factors, including mutation pressure, natural selection, and its two
      hosts, Homo sapiens and Rousettus aegyptiacus. RESULTS: Nucleotide composition
      and relative synonymous codon usage (RSCU) analysis revealed that MARV shows
      mutation bias and prefers U- and A-ended codons to code amino acids. Effective
      number of codons analysis indicated that overall codon usage among MARV genomes
      is slightly biased. The Parity Rule 2 plot analysis showed that GC and AU
      nucleotides were not used proportionally which accounts for the presence of
      natural selection. Codon usage patterns of MARV were also found to be influenced
      by its hosts. This indicates that MARV have evolved codon usage patterns that are
      specific to both of its hosts. Moreover, selection pressure from R. aegyptiacus
      on the MARV RSCU patterns was found to be dominant compared with that from H.
      sapiens. Overall, mutation pressure was found to be the most important and
      dominant force that shapes codon usage patterns in MARV. CONCLUSIONS: To our
      knowledge, this is the first detailed codon usage analysis of MARV and extends
      our understanding of the mechanisms that contribute to codon usage and evolution
      of MARV.

PMID- 26306511
TI  - Acceptability and adherence to Isoniazid preventive therapy in HIV-infected
      patients clinically screened for latent tuberculosis in Dar es Salaam, Tanzania.
AB  - BACKGROUND: Proper adherence to isoniazid preventive therapy (IPT) may depend
      upon the results of tuberculosis (TB) screening test and patients' understanding
      of their risk of developing active TB. We conducted a study to assess the
      acceptability, adherence and completion profile of IPT among HIV-infected
      patients who were clinically screened for latent TB Infection (LTBI). METHODS: A
      multicenter observational study was conducted in Dar es Salaam, Tanzania between
      February 2012 and March 2014. HIV-infected patients 10 years or older were
      clinically screened using a validated symptom-based screening tool to rule out
      active TB. Patients found to have no symptoms in the screening tool were given
      300 mg of isoniazid (INH) daily for 6 months. Patients were followed up monthly
      at the National and Municipal hospital HIV clinics for INH refill and assessment
      of treatment adherence. Adherence was defined as consumption of 90 % or more of
      the monthly prescription of INH. RESULTS: All 1303 invited patients agreed to
      participate in the study. Of 1303 invited HIV-infected patients, 1283 (98.5 %)
      were recruited into the study. Twenty eight (2.2 %) did not complete treatment.
      Those who did not complete the treatment were exclusively adults aged 18 years or
      older, p = 0.302. The overall mean (+/-SD) adherence was 98.9 % (+/-2.9).
      Adherence level among children aged <18 years (92.2 %) was significantly lower
      than adherence level among patients aged 18-29 years (98.3 %), 30-49 years (98.8
      %) and >= 50 years (98.5), p-value = 0.011. Sex, occupation, socio-economic
      status, duration of HIV infection, being on antiretroviral drugs (ARV) and
      duration of ARV use were not associated with adherence. CONCLUSION: IPT is highly
      accepted by HIV infected patients. Patients demonstrated high level of adherence
      to IPT. The level of adherence among children was slightly lower than that among
      adults. IPT non-completers were exclusively adults. Children might need adult
      supervision in taking IPT.

PMID- 26306512
TI  - Mechanisms of the harmful effects of bacterial semen infection on ejaculated
      human spermatozoa: potential inflammatory markers in semen.
AB  - The invasion of the male reproductive tract by microorganisms, and its subsequent
      consequences for sperm fertilizing potential, has been intensely discussed. The
      role of the bacteria that are responsible for the colonization and contamination
      of the male urogenital tract, rather than its infection, in diminished sperm
      parameters raises the most controversy. There are numerous premises suggesting
      that bacterial semen infection is associated with male infertility. However, the
      molecular mechanism by which the fertility is affected is complex and
      multifactorial, and still presents a puzzle. Some authors have suggested that
      direct interactions between bacteria and human spermatozoa facilitate sperm
      immobilization, affect sperm morphology, and thus weaken the ability of sperm to
      fertilize. On the other hand, the massive infiltration of activated leukocytes
      into the inflammatory site may be associated with impairment of sperm fertilizing
      potential, due to oxidative, apoptotic, and immune processes. This review
      presents current research trends and aims to summarize the present knowledge of
      semen inflammation and causative bacterial agents in the male urogenital tract,
      with its consequence on seminological parameters, and male fertility status. 

PMID- 26306513
TI  - Diagnostic markers for germ cell neoplasms: from placental-like alkaline
      phosphatase to micro-RNAs.
AB  - This concise review summarises tissue and serum markers useful for differential
      diagnosis of germ cell tumours (GCT), with focus on the most common testicular
      GCT (TGCT). GCT are characterised by phenotypic heterogeneity due to largely
      retained embryonic pluripotency and aberrant somatic differentiation. TGCT that
      occur in young men are divided into two main types, seminoma and nonseminoma,
      both derived from a pre-invasive germ cell neoplasia in situ (GCNIS), which
      originates from transformed foetal gonocytes. In severely dysgenetic gonads, a
      GCNIS-resembling lesion is called gonadoblastoma. GCT occur rarely in young
      children (infantile GCT) in whom the pathogenesis is different (no
      GCNIS/gonadoblastoma stage) but the histopathological features are similar to the
      adult GCT. The rare spermatocytic tumour of older men is derived from post
      pubertal spermatogonia that clonally expand due to gain-of function mutations in
      survival-promoting genes (e.g. FGFR3, HRAS), thus this tumour has a different
      expression profile than GCNIS-derived TGCT. Clinically most informative
      immunohistochemical markers for GCT, except teratoma, are genes expressed in
      primordial germ cells/gonocytes and embryonic pluripotency-related factors, such
      as placental-like alkaline phosphatase (PLAP), OCT4 (POU5F1), NANOG, AP-2gamma
      (TFAP2C) and LIN28, which are not expressed in normal adult germ cells. Some of
      these markers can also be used for immunocytochemistry to detect GCNIS or
      incipient tumours in semen samples. Gene expression in GCT is regulated in part
      by DNA and histone modifications, and the epigenetic profile of these tumours is
      characterised by genome-wide demethylation, except nonseminomas. In addition, a
      recently discovered mechanism of post-genomic gene expression regulation involves
      small non-coding RNAs, predominantly micro-RNA (miR). Testicular GCT display
      micro-RNA profiles similar to embryonic stem cells. Targeted miRNA-based blood
      tests for miR-371-3 and miR-367 clusters are currently under development and hold
      a great promise for the future. In some patients miR-based tests may be even more
      sensitive than the classical serum tumour markers, beta -chorio-gonadotrophin
      (beta-hCG), alpha-fetoprotein (AFP) and lactate dehydrogenase (LDH), which are
      currently used in the clinic. In summary, research advances have provided
      clinicians with a panel of molecular markers, which allow specific diagnosis of
      various subtypes of GCT and are very useful for early detection at the precursor
      stage and for monitoring of patients during the follow-up. 

PMID- 26306514
TI  - The surgical repair of benign tracheo-oesophageal/pharyngeal fistula in patients
      on mechanical ventilation for severe neurological injuries?.
AB  - Acquired benign tracheo-oesophageal or pharyngeal fistulas (TO/PF) in
      neurological patients who cannot be weaned from mechanical ventilation represent
      a highly demanding clinical problem. We report on 3 patients on intermittent or
      continuous mechanical ventilation who successfully underwent tracheal resection
      and direct repair of the digestive fistula. Postoperative mechanical ventilation
      was provided through a modified silicone Safe-T-Tube, with which the cranial
      branch can be occluded with an internal inflatable balloon, inserted through
      tracheostomy performed at or below the level of the cricoid-tracheal suture line.
      Since the T prosthesis does not have an external cuff in the distal branch, a
      trans-tracheal open ventilation (TOV) technique was adopted. All patients, after
      a period that ranged from 21 h to 38 days from surgery, were restored to
      spontaneous breath; tracheal and oesophageal sutures healed normally. 

PMID- 26306515
TI  - MDCT and MRI of the ampulla of Vater. Part I: technique optimization, normal
      anatomy, and epithelial neoplasms.
AB  - The purpose of this two-part article is to review the cross-sectional anatomy of
      the ampulla and periampullary region, to propose novel and optimized MDCT and MRI
      techniques that allow accurate evaluation of the ampulla of Vater, and to
      summarize the cross-sectional imaging features of benign and malignant ampullary
      conditions. In this first part, we will review the normal anatomy of the
      ampullary region, provide suggestions on how to optimize evaluation of the
      ampullary region by MDCT and MRI, and review the imaging features of select
      epithelial neoplasms of the ampulla. Familiarity with the normal ampullary
      anatomy and the pathologic conditions involving the ampulla, as well as the use
      of optimized MDCT and MRI techniques, may improve the diagnostic accuracy of
      radiologists facing ampullary abnormalities.

PMID- 26306516
TI  - MDCT and MRI of the ampulla of Vater. Part II: non-epithelial neoplasms, benign
      ampullary disorders, and pitfalls.
AB  - The purpose of this two-part article is to review the cross-sectional imaging
      features of benign and malignant ampullary conditions with endoscopic and
      histopathologic correlation and to present the most common pitfalls in the
      evaluation of the ampulla. In this part, we will review the mesenchymal and
      secondary neoplasms of the ampulla, a vast array of benign ampullary conditions,
      causes of bulging papilla, and pitfalls. Familiarity with ampullary pathologic
      conditions and pitfalls, as well as the use of optimized MDCT and MRI techniques,
      may improve the diagnostic accuracy of radiologists facing ampullary
      abnormalities. 

PMID- 26306517
TI  - Treatment patterns and outcomes in the prophylaxis of chemotherapy-induced
      (febrile) neutropenia with biosimilar filgrastim (the MONITOR-GCSF study).
AB  - PURPOSE: The purpose of this study is to examine the real-world treatment
      patterns and outcomes of chemotherapy-induced (febrile) neutropenia (chemotherapy
      induced (CIN)/febrile neutropenia (FN)) prophylaxis with biosimilar filgrastim
      (Zarzio(r)). METHODS: MONITOR-GCSF is an international (12 countries), multi
      center (140), prospective (max. six cycles), observational, open-label, pharmaco
      epidemiologic study of cancer patients (n = 1447) treated with myelosuppressive
      chemotherapy across a total of 6,213 cycles and receiving prophylaxis with
      Zarzio(r). Data were analyzed using both the patient and cycle as unit of
      analysis. RESULTS: Most (72.3 %) received primary prophylaxis; dosed mainly (53.2
      %) at 30 MIU but differentiated by weight, chemotoxicity, and tumor type; and
      mainly (53.2 %) initiated in the 24-72h post-chemotherapy window but
      differentiated by prophylaxis type, tumor type, and chemotoxicity and for
      modal/median duration of 5 days. Relative to European Organisation for Research
      and Treatment of Cancer (EORTC) guidelines, 56.6 % were correctly prophylacted,
      17.4 % under-prophylacted, and 26.0 % over-prophylacted. The following incidence
      rates were recorded: CIN grade 4 13.2 % of patients and 3.9 % of cycles, FN 5.9 %
      of patients and 1.4 % of cycles, CIN/FN-related hospitalizations 6.1 % of
      patients and 1.5 % of cycles, CIN/FN-related chemotherapy disturbances 9.5 % of
      patients and 2.8 % of cycles, and composite outcomes index 22.3 % of patients and
      6.7 % of cycles. Rates varied by type of prophylaxis and tumor, chemotoxicity,
      initiation day, and prophylaxis duration. There were 1834 musculoskeletal events
      with 24.7 % of patients reporting bone pain of any grade (mostly mild to
      moderate), and 148 adverse drug reactions, including 4 serious, were recorded in
      76 patients. CONCLUSIONS: The clinical and safety outcomes are well within the
      range of historically reported data for originator filgrastim underscoring the
      clinical effectiveness and safety of biosimilar filgrastim in daily clinical
      practice.

PMID- 26306518
TI  - An online self-care education program to support patients after total
      laryngectomy: feasibility and satisfaction.
AB  - PURPOSE: The purpose of this study was to investigate the feasibility of an
      online self-care education program supporting early rehabilitation of patients
      after total laryngectomy (TLPs) and factors associated with satisfaction.
      METHODS: Health care professionals (HCPs) were invited to participate and to
      recruit TLPs. TLPs were informed on the self-care education program "In Tune
      without Cords" (ITwC) after which they gained access. A study specific survey was
      used (at baseline T0 and postintervention T1) on TLPs' uptake. Usage,
      satisfaction (general impression, willingness to use, user-friendliness,
      satisfaction with self-care advice and strategies, Net Promoter Score (NPS)),
      sociodemographic, and clinical factors were analyzed. RESULTS: HCPs of 6 out of 9
      centers (67% uptake rate) agreed to participate and recruited TLPs. In total, 55
      of 75 TLPs returned informed consent and the baseline T0 survey and were provided
      access to ITwC (73% uptake rate). Thirty-eight of these 55 TLPs used ITwC and
      completed the T1 survey (69% usage rate). Most (66%) TLPs were satisfied (i.e.,
      score >=7 (scale 1-10) on 4 survey items) with the self-care education program
      (mean score 7.2, SD 1.1). NPS was positive (+5). Satisfaction with the self-care
      education program was significantly associated with (higher) educational level
      and health literacy skills (P = .004, P = .038, respectively). No significant
      association was found with gender, age, marital status, employment status,
      Internet use, Internet literacy, treatment modality, time since total
      laryngectomy, and quality of life. CONCLUSION: The online self-care education
      program ITwC supporting early rehabilitation was feasible in clinical practice.
      In general, TLPs were satisfied with the program.

PMID- 26306519
TI  - Transition to the new role of caregiving for families of patients with breast
      cancer: a qualitative descriptive exploratory study.
AB  - BACKGROUND: Families, especially in Eastern and Muslim countries, routinely
      accept the responsibility of caring for cancer patients. This study describes the
      transition to the new role of caregiving from the perspective of family
      caregivers in Iran as part of the current trend of recognizing the experiences of
      family members of breast cancer patients from different cultural perspectives.
      MATERIALS AND METHODS: A descriptive exploratory qualitative research approach
      was used to investigate the experiences of family caregivers of patients with
      breast cancer in the transition to caregiving. The subjects were 23 family
      caregivers of breast cancer patients referred to cancer centers at Isfahan
      University hospitals who were selected by purposive sampling. Data was gathered
      through in-depth interviews. Interview transcripts were analyzed using
      conventional content analysis with an inductive approach. RESULTS: Data analysis
      identified the following categories: grasping a new situation without
      preparation, perceived inefficiency, infinite absence, and abandoned in the role.
      Caregivers believed that they were not prepared for their new circumstances and
      did not have the necessary competence and capabilities to meet the challenges of
      caregiving. They experienced negative consequences resulting from the difficult
      responsibility of caregiving. Moreover, they believed that they received limited
      support from relatives, health-care providers, and the community. CONCLUSION: The
      transition to the new role of caregiving is affected by experiences specific to
      the conditions of the caretakers. When these conditions can be understood and
      identified, it is possible to provide detailed information for policymaking and
      planning for family-centered care.

PMID- 26306521
TI  - Sexual function, depression, and quality of life in patients with cervical
      cancer.
AB  - PURPOSE: The purpose of this study was to examine the level of sexual function,
      depression, and quality of life in cervical cancer patients. METHODS: This
      descriptive, correlational, cross-sectional study was conducted at E Hospital,
      Seoul. A total of 137 women diagnosed with cervical cancer completed a structured
      questionnaire. Sexual function was measured with the Female Sexual Function Index
      (FSFI), depression with the Hospital Anxiety and Depression Scale (HADS), and
      quality of life with the Functional Assessment of Cancer Therapy-General version
      4 (FACT-G). Descriptive statistics, ANOVA, Scheffe's tests, and Pearson
      correlations were computed with SPSS Win 21.0. RESULTS: The participants
      experienced sexual dysfunction (4.83 +/- 4.16) and moderate to severe depression
      (11.08 +/- 5.06). The mean score of quality of life was 57.33 +/- 8.47. Sexual
      function had a negative relationship with depression, while having a positive one
      with quality of life (p < .001). Also, in relation with subcategories of quality
      of life, sexual function was positively correlated with physical well-being,
      social well-being, and functional well-being (p = .001), but not with
      psychological well-being (p = .223). CONCLUSION: This study showed that cervical
      cancer patients with lower sexual function tended to have lower quality of life
      and higher levels of depression. Thus, clinical nurses should develop and
      implement interventions to enhance sexual function for patients diagnosed with
      cervical cancer.

PMID- 26306520
TI  - Pegfilgrastim administration after 24 or 72 or 96 h to allow dose-dense
      anthracycline- and taxane-based chemotherapy in breast cancer patients: a single
      center experience within the GIM2 randomized phase III trial.
AB  - PURPOSE: To evaluate the safest timing of pegfilgrastim administration in dose
      dense anthracycline- and taxane-based chemotherapy, three different cohorts of
      patients enrolled in the Gruppo Italiano Mammella (GIM) 2 study and treated at
      the coordinating center received pegfilgrastim 24 h (cohort A) or 72 h (cohort B)
      or 96 h (cohort C) after chemotherapy. METHODS: A total of 41 patients were
      included. The safety of pegfilgrastim administration in terms of occurrence of
      early and late leukocytosis and the behavior of white blood cells (WBC) counts in
      the three cohorts across all chemotherapy cycles were evaluated. Anthracycline
      and taxane cycles were analyzed separately. RESULTS: The occurrence of early
      leukocytosis was a more common event in patients in cohort A in both
      anthracycline and taxane cycles (75 and 66.7%) as compared to cohort B (50 and
      60%) and cohort C (66.7 and 33.3%). More patients in cohort C developed late
      leukocytosis in both anthracycline and taxane cycles (50 and 100%) as compared to
      cohort A (0 and 66.7%) and cohort B (35.7 and 86.7%). Patients in cohort A
      experienced the highest median value of WBC count 24 h after pegfilgrastim
      administration in both anthracycline and taxane cycles (61.2 * 10(3)/MUl and 67.8
      * 10(3)/MUl). Patients in cohort C experienced the highest median value of WBC
      count at day 13 in both anthracycline and taxane cycles (19.4 * 10(3)/MUl and
      24.2 * 10(3)/MUl). CONCLUSIONS: For the prevention of leukocytosis, the safest
      timing of pegfilgrastim administration based on WBC count in dose-dense
      anthracycline- and taxane-based regimens seems to be 72 h after chemotherapy.
      TRIAL REGISTRATION: This study is registered with
      https://clinicaltrials.gov/ct2/show/NCT00433420.

PMID- 26306522
TI  - Presentation patterns and outcomes of patients with cancer accessing care in
      emergency departments in Victoria, Australia.
AB  - PURPOSE: People with cancer attend emergency departments (EDs) for many reasons.
      Improved understanding of the specific needs of these patients may assist in
      optimizing health service delivery. ED presentation and hospital utilization
      characteristics were explored for people with cancer and compared with those
      patients without cancer. METHODS: This descriptive, retrospective, multicentre
      cohort study used hospital administrative data. Descriptive and inferential
      statistics were used to summarise and compare ED presentation characteristics
      amongst cancer and non-cancer groups. Predictive analyses were used to identify
      ED presentation features predictive of hospital admission for cancer patients.
      Outcomes of interest were level of acuity, ED and inpatient length of stay, re
      presentation rates and admission rates amongst cancer patients and non-cancer
      patients. RESULTS: ED (529,377) presentations occurred over the 36 months, of
      which 2.4% (n = 12,489) were cancer-related. Compared with all other attendances,
      cancer-related attendances had a higher level of acuity, requiring longer
      management time and length of stay in ED. Re-presentation rates for people with
      cancer were nearly double those of others (64 vs 33%, p < 0.001), with twice the
      rate of hospital admission (90 vs 46%, p < 0.001), longer inpatient length of
      stay (5.6 vs 2.8 days, p < 0.001) and had higher inpatient mortality (7.9 vs
      1.0%, p < 0.001). Acuity and arriving by ambulance were significant predictors of
      hospital admission, with cancer-related attendances having ten times the odds of
      admission compared to other attendances (OR = 10.4, 95% CI 9.8-11.1).
      CONCLUSIONS: ED presentations by people with cancer represent a more urgent,
      complex caseload frequently requiring hospital admission when compared to other
      presentations, suggesting that for optimal cancer care, close collaboration and
      integration of oncology, palliative care and emergency medicine providers are
      needed to improve pathways of care.

PMID- 26306523
TI  - The financial hazard of personalized medicine and supportive care.
AB  - Personalized medicine is revolutionizing the delivery of oncological care,
      promising benefits both at the patient and health system levels. The cost of
      targeted therapies, unfortunately, is becoming more expensive and unaffordable.
      Where supportive care in cancer concerns the prevention and management of the
      adverse effects of cancer and its treatment and is the thrust of the
      Multinational Association of Supportive Care in Cancer, financing of and value in
      personalized medicine is an important area of research and engagement for the
      association. Discussing patients' concerns with and identifying those at most
      risk for the financial hazard of cancer treatment and offering financial
      counseling and assistance and/or referral to support networks are potential key
      areas for (exploring and providing) better supportive care. The time is now to
      turn the concern of patients and their carers, providers, and other advocates
      regarding the affordability of cancer treatment into a collective cause towards
      coordinated action. 

PMID- 26306525
TI  - The Diabetes Educator and the Diabetes Self-management Education Engagement: The
      2015 National Practice Survey.
AB  - PURPOSE: The National Practice Study (NPS) is conducted biannually to assess
      current diabetes education practices in the United States with the goal of
      understanding current trends in the work in which diabetes educators engage.
      METHODS: The 2015 NPS contained 54 questions about the individuals providing
      diabetes education, people with diabetes participating in education, and programs
      providing the education. The survey was sent electronically to approximately 21
      975 people who were members of the American Association of Diabetes Educators
      (AADE) or who were Certified Diabetes Educators with the National Certification
      Board for Diabetes Educators but were not currently AADE members. In addition,
      both the AADE and the National Certification Board for Diabetes Educators
      promoted participation in the NPS via social media. The combination of efforts
      resulted in completion of the survey by 4855 respondents. Testing was completed
      with a significance level of 0.05 or 95% confidence. RESULTS: Diabetes educators
      continue to represent a diverse group of health care professionals-nurses (50%),
      dietitians (35%), pharmacists (6%), and others (6%). By far, the most commonly
      held credential for the specialty continues to be the Certified Diabetes Educator
      (86%), with only 5% of survey respondents indicating that they held the Board
      Certified-Advanced Diabetes Management credential. Diabetes educators are working
      with individuals across the diabetes continuum, as well as with people who do not
      have diabetes but have other chronic conditions. The data demonstrate that much
      of the diabetes educator's work with people with diabetes is beyond the first
      year of diagnosis. Diabetes educators are increasingly seen to be providing a
      broader array of the integrated AADE7 Self-Care BehaviorsTM. CONCLUSIONS: The
      specialty of diabetes educator continues to be populated by a professionally
      diverse workforce, meeting the needs of people across a wide spectrum. Diabetes
      educators can be found providing services in primary prevention of diabetes,
      education and management for those diagnosed with diabetes, prevention of
      secondary complications, and more complex management of diabetes and its
      secondary complications. While diabetes educators were found to work with those
      newly diagnosed with diabetes, they continue to engage with people with diabetes
      at various times other than the year that they were diagnosed. There are still
      issues with participant readiness, as evidenced by program completion rates.
      Nonetheless, diabetes educators are increasingly seen to be providing the
      integrated engagement that is needed to better ensure that people with diabetes
      attain and maintain competency in self-management skills.

PMID- 26306524
TI  - Amorphous solid dispersion technique for improved drug delivery: basics to
      clinical applications.
AB  - Solid dispersion has emerged as a method of choice and has been extensively
      investigated to ascertain the in vivo improved performance of many drug
      formulations. It generally involves dispersion of drug in amorphous particles
      (clusters) or in crystalline particles. Comparatively, in the last decade,
      amorphous drug-polymer solid dispersion has evolved into a platform technology
      for delivering poorly water-soluble small molecules. However, the success of this
      technique in the pharmaceutical industry mainly relies on different drug-polymer
      attributes like physico-chemical stability, bioavailability and
      manufacturability. The present review showcases the efficacy of amorphous solid
      dispersion technique in the research and evolution of different drug formulations
      particularly for those with poor water soluble properties. Apart from the
      numerous mechanisms of action involved, a comprehensive summary of different key
      parameters required for the solubility enhancement and their translational
      efficacy to clinics is also emphasized. 

PMID- 26306526
TI  - HN Protein of Newcastle Disease Virus Induces Apoptosis Through SAPK/JNK Pathway.
AB  - Many viral proteins are responsible for causing induction of apoptosis in the
      target cells. Hemagglutinin neuraminidase (HN), a multifunctional protein of
      Newcastle disease virus (NDV), is one of such proteins. The present study was
      undertaken to determine the apoptotic potential of the HN gene in cultured human
      cervical cancer cell line (HeLa cell) and to elucidate the molecular mechanisms
      involved. The results of the study indicate that HN protein causes apoptosis in
      HeLa cells, as observed by the translocation of Phosphatidylserine, activation of
      caspases, cleavage of poly (ADP-ribose) polymerase (PARP), and DNA fragmentation.
      Further, we report that expression of HN protein upregulates the SAPK/JNK pathway
      leading to transactivation of c-Jun which in turn activates apoptosis signaling.
      The results of our study provide an insight into the mechanism through which HN
      induces apoptosis.

PMID- 26306527
TI  - Characterization of Inulin Hydrolyzing Enzyme(s) in Oleaginous Yeast Trichosporon
      cutaneum in Consolidated Bioprocessing of Microbial Lipid Fermentation.
AB  - Oleaginous yeast Trichosporon cutaneum CGMCC 2.1374 was found to utilize inulin
      directly for microbial lipid fermentation without a hydrolysis step. The
      potential inulinase-like enzyme(s) in T. cutaneum CGMCC 2.1374 were characterized
      and compared with other inulinase enzymes produced by varied yeast strains. The
      consolidated bioprocessing (CBP) for lipid accumulated using inulin was optimized
      with 4.79 g/L of lipid produced from 50 g/L inulin with the lipid content of
      33.6% in dry cells. The molecular weight of the enzyme was measured which was
      close to invertase in Saccharomyces cerevisiae. The study provided information
      for inulin hydrolyzing enzyme(s) in oleaginous yeasts, as well as a preliminary
      CBP process for lipid production from inulin feedstock.

PMID- 26306528
TI  - Cloning, Expression, and Characterization of Capra hircus Golgi alpha-Mannosidase
      II.
AB  - Golgi alpha-mannosidase II (GMII), a key glycosyl hydrolase in the N-linked
      glycosylation pathway, has been demonstrated to be closely associated with the
      genesis and development of cancer. In this study, we cloned cDNA-encoding Capra
      hircus GMII (chGMII) and expressed it in Pichia pastoris expression system. The
      chGMII cDNA contains an open reading frame of 3432 bp encoding a polypeptide of
      1144 amino acids. The deduced molecular mass and pI of chGMII was 130.5 kDa and
      8.04, respectively. The gene expression profile analysis showed GMII was the
      highest expressed gene in the spleen. The recombinant chGMII showed maximum
      activity at pH 5.4 and 42  degrees C and was activated by Fe(2+), Zn(2+), Ca(2+),
      and Mn(2+) and strongly inhibited by Co(2+), Cu(2+), and EDTA. By homology
      modeling and molecular docking, we obtained the predicted 3D structure of chGMII
      and the probable binding modes of chGMII-GnMan5Gn, chGMII-SW. A small cavity
      containing Tyr355 and zinc ion fixed by residues Asp290, His176, Asp178, and
      His570 was identified as the active center of chGMII. These results not only
      provide a clue for clarifying the catalytic mechanism of chGMII but also lay a
      theoretical foundation for subsequent investigations in the field of anticancer
      therapy for mammals. 

PMID- 26306529
TI  - A Novel and Effective Streptomyces sp. N2 Against Various Phytopathogenic Fungi.
AB  - Phytopathogenic fungi would induce a variety of plant diseases, resulting in a
      severe reduction of agricultural output. However, the current plant disease
      control is mainly dependent on the environmentally and healthily hazardous
      chemical fungicides. Thus, the present work aimed to isolate an effective
      antagonistic microorganism against various soilborne phytopathogenic fungi. By
      dual culture with Rhizoctonia solani, a novel Streptomyces specie, Streptomyces
      sp. N2, was screened out from a total of 167 isolated actinomycetes, which
      displayed a strong inhibitory effect on R. solani (26.85 +/- 1.35 mm of
      inhibition zone diameter). By means of macroporous resin and silica gel column
      chromatography coupled with preparative HPLC, an antifungal metabolite (3-methyl
      3,5-amino-4-vinyl-2-pyrone, C6H7O2N) was isolated and purified from Streptomyces
      sp. N2. The bioassay results showed that the purified antifungal metabolite could
      not only possess a broad-spectrum inhibitory effect on a range of plant
      pathogenic fungi in vitro (e.g., R. solani, Pyricularia grisea, Fusarium
      oxysporum f. sp. niveum, F. oxysporum f. sp. vasinfectum, Penicillium italicum,
      and Colletotrichum gloeosporioides), but also had a significantly effective in
      vivo biocontrol efficacy on grape fruits anthracnose caused by C.
      gloeosporioides. Microscopic observation indicated that the antifungal metabolite
      from Streptomyces sp. N2 would exert its antimicrobial activity by disorganizing
      the cytoplasmic organelles of phytopathogenic fungi. The above results suggested
      that Streptomyces sp. N2 was one of promising fungicide for biocontrol of fungal
      plant diseases, especially due to its broad-spectrum and effective antagonist on
      various plant pathogens. 

PMID- 26306530
TI  - Antioxidant Capacity of Poly(Ethylene Glycol) (PEG) as Protection Mechanism
      Against Hydrogen Peroxide Inactivation of Peroxidases.
AB  - The ability of poly(ethylene glycol) (PEG) to protect enzymatic peroxidase
      activity was determined for horseradish peroxidase (HRP), versatile peroxidase
      (VP), commercial Coprinus peroxidase (BP), and chloroperoxidase (CPO). The
      operational stability measured as the total turnover number was determined for
      the four peroxidases. The presence of PEG significantly increased the operational
      stability of VP and HRP up to 123 and 195%, respectively, and dramatically
      increased the total turnover number of BP up to 597%. Chloroperoxidase was not
      protected by PEG, which may be due to the different oxidation mechanism, in which
      the oxidation is mediated by hypochlorous ion instead of free radicals as in the
      other peroxidases. The presence of PEG does not protect the enzyme when incubated
      only in the presence of H2O2 without reducing substrate. The catalytic constants
      (k cat) are insensitive to the presence of PEG, suggesting that the protection
      mechanism is not due to a competition between the PEG and the substrate as
      electron donors. On the other hand, PEG showed to have a significant antioxidant
      capacity. Thus, we conclude that the protection mechanism for peroxidases of PEG
      is based in its antioxidant capacity with which it is able scavenge or drain
      radicals that are harmful to the protein.

PMID- 26306532
TI  - [Not Available].

PMID- 26306533
TI  - Physical origin of DNA unzipping.
AB  - In DNA transcription, the base pairs are unzipped in response to the enzymatic
      forces, separating apart two intertwined nucleotide strands. Consequently, the
      double-stranded DNA (dsDNA), in which two nucleotide strands wind about each
      other, transits structurally to the single-stranded DNA (ssDNA) in which two
      nucleotide strands are completely unwound and separated. The large interstrand
      separation is intimately related to the softening nucleotide strands. This
      conceptual framework is reinforced with the flow of the bending modulus toward
      zero under recursion relations derived from the momentum shell renormalization
      group. Interestingly, the stretch modulus remains the same under recursion
      relations. The renormalization of the bending modulus to zero has a profound
      implication that ssDNA has the shorter bending persistence length than does dsDNA
      in accordance with experiments. 

PMID- 26306534
TI  - Modeling of toxin-antibody interaction and toxin transport toward the endoplasmic
      reticulum.
AB  - A model for toxin-antibody interaction and toxin trafficking towards the
      endoplasmic-reticulum is presented. Antibody and toxin (ricin) initially are
      delivered outside the cell. The model involves: the pinocytotic (cellular
      drinking) and receptor-mediated toxin internalization modes from the
      extracellular into the intracellular domain, its exocytotic excretion from the
      cytosol back to the extracellular medium, the intact toxin retrograde transport
      to the endoplasmic reticulum, the anterograde toxin movement outward from the
      cell across the plasma membrane, the lysosomal toxin degradation, and the toxin
      clearance (removal from the system) flux. The model consists of a set of coupled
      PDEs. Using an averaging procedure, the model is reduced to a system of coupled
      ODEs. Both PDEs and ODEs systems are solved numerically. Numerical results are
      illustrated by figures and discussed. 

PMID- 26306531
TI  - Selection Against Maternal microRNA Target Sites in Maternal Transcripts.
AB  - In animals, before the zygotic genome is expressed, the egg already contains gene
      products deposited by the mother. These maternal products are crucial during the
      initial steps of development. In Drosophila melanogaster, a large number of
      maternal products are found in the oocyte, some of which are indispensable. Many
      of these products are RNA molecules, such as gene transcripts and ribosomal RNAs.
      Recently, microRNAs (small RNA gene regulators) have been detected early during
      development and are important in these initial steps. The presence of some
      microRNAs in unfertilized eggs has been reported, but whether they have a
      functional impact in the egg or early embryo has not being explored. I have
      extracted and sequenced small RNAs from Drosophila unfertilized eggs. The
      unfertilized egg is rich in small RNAs and contains multiple microRNA products.
      Maternal microRNAs often are encoded within the intron of maternal genes,
      suggesting that many maternal microRNAs are the product of transcriptional
      hitchhiking. Comparative genomics analyses suggest that maternal transcripts tend
      to avoid target sites for maternal microRNAs. I also developed a microRNA target
      mutation model to study the functional impact of polymorphisms at microRNA target
      sites. The analysis of Drosophila populations suggests that there is selection
      against maternal microRNA target sites in maternal transcripts. A potential role
      of the maternal microRNA mir-9c in maternal-to-zygotic transition is also
      discussed. In conclusion, maternal microRNAs in Drosophila have a functional
      impact in maternal protein-coding transcripts. 

PMID- 26306535
TI  - Long term NSAIDs are associated with lower colorectal cancer risk, study shows.

PMID- 26306537
TI  - Antitumor Activity of Doxorubicin-Loaded Carbon Nanotubes Incorporated
      Poly(Lactic-Co-Glycolic Acid) Electrospun Composite Nanofibers.
AB  - The drug-loaded composite electrospun nanofiber has attracted more attention in
      biomedical field, especially in cancer therapy. In this study, a composite
      nanofiber was fabricated by electrospinning for cancer treatment. Firstly, the
      carbon nanotubes (CNTs) were selected as carriers to load the anticancer drug
      doxorubicin (DOX) hydrochloride. Secondly, the DOX-loaded CNTs (DOX@CNTs) were
      incorporated into the poly(lactic-co-glycolic acid) (PLGA) nanofibers via
      electrospinning. Finally, a new drug-loaded nanofibrous scaffold (PLGA/DOX@CNTs)
      was formed. The properties of the prepared composite nanofibrous mats were
      characterized by various techniques. The release profiles of the different DOX
      loaded nanofibers were measured, and the in vitro antitumor efficacy against HeLa
      cells was also evaluated. The results showed that DOX-loaded CNTs can be readily
      incorporated into the nanofibers with relatively uniform distribution within the
      nanofibers. More importantly, the drug from the composite nanofibers can be
      released in a sustained and prolonged manner, and thereby, a significant
      antitumor efficacy in vitro is obtained. Thus, the prepared composite nanofibrous
      mats are a promising alternative for cancer treatment. 

PMID- 26306536
TI  - A review on potential neurotoxicity of titanium dioxide nanoparticles.
AB  - As the rapid development of nanotechnology in the past three decades, titanium
      dioxide nanoparticles (TiO2 NPs), for their peculiar physicochemical properties,
      are widely applied in consumer products, food additives, cosmetics, drug
      carriers, and so on. However, little is known about their potential exposure and
      neurotoxic effects. Once NPs are unintentionally exposed to human beings, they
      could be absorbed, and then accumulated in the brain regions by passing through
      the blood-brain barrier (BBB) or through the nose-to-brain pathway, potentially
      leading to dysfunctions of central nerve system (CNS). Besides, NPs may affect
      the brain development of embryo by crossing the placental barrier. A few in vivo
      and in vitro researches have demonstrated that the morphology and function of
      neuronal or glial cells could be impaired by TiO2 NPs which might induce cell
      necrosis. Cellular components, such as mitochondrial, lysosome, and cytoskeleton,
      could also be influenced as well. The recognition ability, spatial memory, and
      learning ability of TiO2 NPs-treated rodents were significantly impaired, which
      meant that accumulation of TiO2 NPs in the brain could lead to neurodegeneration.
      However, conclusions obtained from those studies were not consistent with each
      other as researchers may choose different experimental parameters, including
      administration ways, dosage, size, and crystal structure of TiO2 NPs. Therefore,
      in order to fully understand the potential risks of TiO2 NPs to brain health,
      figure out research areas where further studies are required, and improve its bio
      safety for applications in the near future, how TiO2 NPs interact with the brain
      is investigated in this review by summarizing the current researches on
      neurotoxicity induced by TiO2 NPs. 

PMID- 26306538
TI  - CMOS-Compatible Top-Down Fabrication of Periodic SiO2 Nanostructures using a
      Single Mask.
AB  - We propose a CMOS-compatible top-down fabrication technique of highly-ordered and
      periodic SiO2 nanostructures using a single amorphous silicon (alpha-Si) mask
      layer. The alpha-Si mask pattern is precisely transferred into the underlying
      SiO2 substrate material with a high fidelity by a novel top-down fabrication. It
      is the first time for alpha-Si film used as an etch mask to fabricate SiO2
      nanostructures including nanoline, nanotrench, and nanohole arrays. It is
      observed that the alpha-Si mask can significantly reduce the pattern edge
      roughness and achieve highly uniform and smooth sidewalls. This behavior may be
      attributed to the presence of high concentration of dangling bonds in alpha-Si
      mask surface. By controlling the process condition, it is possible to achieve a
      desired vertical etched profile with a controlled size. Our results demonstrate
      that SiO2 pattern as small as sub-20 nm may be achievable. The obtained SiO2
      pattern can be further used as a nanotemplate to produce periodic or more complex
      silicon nanostructures. Moreover, this novel top-down approach is a potentially
      universal method that is fully compatible with the currently existing Si-based
      CMOS technologies. It offers a greater flexibility for the fabrication of various
      nanoscale devices in a simple and efficient way. 

PMID- 26306539
TI  - An Ingenious Super Light Trapping Surface Templated from Butterfly Wing Scales.
AB  - Based on the super light trapping property of butterfly Trogonoptera brookiana
      wings, the SiO2 replica of this bionic functional surface was successfully
      synthesized using a simple and highly effective synthesis method combining a sol
      gel process and subsequent selective etching. Firstly, the reflectivity of
      butterfly wing scales was carefully examined. It was found that the whole
      reflectance spectroscopy of the butterfly wings showed a lower level (less than
      10 %) in the visible spectrum. Thus, it was confirmed that the butterfly wings
      possessed a super light trapping effect. Afterwards, the morphologies and
      detailed architectures of the butterfly wing scales were carefully investigated
      using the ultra-depth three-dimensional (3D) microscope and field emission
      scanning electronic microscopy (FESEM). It was composed by the parallel ridges
      and quasi-honeycomb-like structure between them. Based on the biological
      properties and function above, an exact SiO2 negative replica was fabricated
      through a synthesis method combining a sol-gel process and subsequent selective
      etching. At last, the comparative analysis of morphology feature size and the
      reflectance spectroscopy between the SiO2 negative replica and the flat plate was
      conducted. It could be concluded that the SiO2 negative replica inherited not
      only the original super light trapping architectures, but also the super light
      trapping characteristics of bio-template. This work may open up an avenue for the
      design and fabrication of super light trapping materials and encourage people to
      look for more super light trapping architectures in nature. 

PMID- 26306540
TI  - [Magnetic resonance imaging. Density equalizing mapping analysis of global
      research architecture].
AB  - BACKGROUND: Despite the great medical importance, there is still no comprehensive
      scientometric analysis regarding the results of magnetic resonance imaging (MRI)
      and the development of the importance for the healthcare system. AIMS: This paper
      evaluated and analyzed the entire research publication results on the topic of
      MRI for the period 1981-2007 based on scientometric methods and parameters.
      MATERIAL AND METHODS: A scientometric analysis (database: ISI Web of Science 1981
      2007, search terms MRI and magnetic resonance imaging) was performed. The
      following parameters were analyzed: number of publications, countries of
      publication, number of citations, citation rate and collaborations, using various
      analytical and display techniques, including density equalizing map projections.
      RESULTS: Most of the 49,122 publications on MRI could be attributed to the USA
      (32.5 %), which also has the most cooperative collaborations. Within Europe,
      Germany (10.3 %) is the country with the highest number of publications followed
      by the UK (9.3 %). The western industrialized nations dominate over the rest of
      the world in terms of scientific developments of MRI. The thematic focus of the
      publications lies in the fields of radiology and neuroscience. In addition to the
      journal Neurology most scientific articles were published in Magnetic Resonance
      in Medicine and Circulation. DISCUSSION: The results show that the current trend
      is continuing and the scientific interest in MRI is continuously increasing.

PMID- 26306541
TI  - Contrasting the roles of the I-II loop gating brake in CaV3.1 and CaV3.3 calcium
      channels.
AB  - Low-voltage-activated CaV3 channels are distinguished among other voltage
      activated calcium channels by the most negative voltage activation threshold. The
      voltage dependence of current activation is virtually identical in all three CaV3
      channels while the current kinetics of the CaV3.3 current is one order slower
      than that of the CaV3.1 and CaV3.2 channels. We have analyzed the voltage
      dependence and kinetics of charge (Q) movement in human recombinant CaV3.3 and
      CaV3.1 channels. The voltage dependence of voltage sensor activation (Qon-V) of
      the CaV3.3 channel was significantly shifted with respect to that of the CaV3.1
      channel by +18.6 mV and the kinetic of Qon activation in the CaV3.3 channel was
      significantly slower than that of the CaV3.1 channel. Removal of the gating brake
      in the intracellular loop connecting repeats I and II in the CaV3.3 channel in
      the ID12 mutant channel shifted the Qon-V relation to a value even more negative
      than that for the CaV3.1 channel. The kinetic of Qon activation was not
      significantly different between ID12 and CaV3.1 channels. Deletion of the gating
      brake in the CaV3.1 channel resulted in a GD12 channel with the voltage
      dependence of the gating current activation significantly shifted toward more
      negative potentials. The Qon kinetic was not significantly altered. ID12 and GD12
      mutants did not differ significantly in voltage dependence nor in the kinetic of
      voltage sensor activation. In conclusion, the putative gating brake in the
      intracellular loop connecting repeats I and II controls the gating current of the
      CaV3 channels. We suggest that activation of the voltage sensor in domain I is
      limiting both the voltage dependence and the kinetics of CaV3 channel activation.

PMID- 26306542
TI  - Effects of the Danish saturated fat tax on the demand for meat and dairy
      products.
AB  - OBJECTIVE: Taxation of unhealthy food is considered a regulation tool to improve
      diets. In 2011 Denmark introduced a tax on saturated fat in food products, the
      first country in the world to do so. The objective of the present paper is to
      investigate the effects of the tax on consumers' intake of saturated fat within
      three different types of food product group: minced beef, regular cream and sour
      cream. DESIGN: We use an augmented version of the Linearized Almost Ideal Demand
      System (LAIDS) functional form for econometric analysis, allowing for tax-induced
      structural breaks. SETTING: Data originate from one of the largest retail chains
      in Denmark (Coop Danmark) and cover January 2010 to October 2012, with monthly
      records of sales volume, sales revenue and information about specific campaigns
      from 1293 stores. RESULTS: The Danish fat tax had an insignificant or small
      negative effect on the price for low- and medium-fat varieties, and led to a 13
      16 % price increase for high-fat varieties of minced beef and cream products. The
      tax induced substitution effects, budget effects and preference change effects on
      consumption, yielding a total decrease of 4-6 % in the intake of saturated fat
      from minced beef and regular cream, and a negligible effect on the intake from
      sour cream. CONCLUSIONS: The Danish introduction of a tax on saturated fat in
      food in October 2011 had statistically significant effects on the sales of fat in
      minced beef and cream products, but the tax seems to have reduced the beyond
      recommendation saturated fat intake to only a limited extent.

PMID- 26306543
TI  - Superconducting magnetoresistance in ferromagnet/superconductor/ferromagnet
      trilayers.
AB  - Magnetoresistance is a multifaceted effect reflecting the diverse transport
      mechanisms exhibited by different kinds of plain materials and hybrid
      nanostructures; among other, giant, colossal, and extraordinary magnetoresistance
      versions exist, with the notation indicative of the intensity. Here we report on
      the superconducting magnetoresistance observed in
      ferromagnet/superconductor/ferromagnet trilayers, namely Co/Nb/Co trilayers,
      subjected to a parallel external magnetic field equal to the coercive field. By
      manipulating the transverse stray dipolar fields that originate from the out-of
      plane magnetic domains of the outer layers that develop at coercivity, we can
      suppress the supercurrent of the interlayer. We experimentally demonstrate a
      scaling of the magnetoresistance magnitude that we reproduce with a closed-form
      phenomenological formula that incorporates relevant macroscopic parameters and
      microscopic length scales of the superconducting and ferromagnetic structural
      units. The generic approach introduced here can be used to design novel cryogenic
      devices that completely switch the supercurrent 'on' and 'off', thus exhibiting
      the ultimate magnetoresistance magnitude 100% on a regular basis. 

PMID- 26306544
TI  - The Neuraminidase Stalk Deletion Serves as Major Virulence Determinant of H5N1
      Highly Pathogenic Avian Influenza Viruses in Chicken.
AB  - Highly pathogenic avian influenza viruses (HPAIV) cause devastating losses in
      gallinaceous poultry world-wide and raised concerns of a novel pandemic. HPAIV
      develop from low-pathogenic precursors by acquisition of a polybasic HA cleavage
      site (HACS), the prime virulence determinant. Beside that HACS, other adaptive
      changes accumulate in those precursors prior to transformation into an HPAIV.
      Here, we aimed to unravel such virulence determinants in addition to the HA gene.
      Stepwise reduction of HPAIV genes revealed that the HPAIV HA and NA form a
      minimum set of virulence determinants, sufficient for a lethal phenotype in
      chicken. Abolishing the NA stalk deletion considerably reduced lethality and
      prevented transmission. Conversely, the analogous stalk deletion reconstructed in
      the NA of an LPAIV reassortant carrying only the HPAIV HA resulted in 100%
      lethality both after primary and contact infection. Remarkably, the unmodified
      LPAIV NA with its long stalk, when exclusively introduced into the H5N1 HPAIV,
      still enabled high virulence and efficient transmission. Therefore, irrespective
      of an NA stalk deletion, minor virulence determinants in addition to the
      essential polybasic HACS contribute to high virulence, whereas the NA stalk
      deletion alone may serve as major virulence determinant. 

PMID- 26306545
TI  - A retrospective comparison of ropivacaine and 2-chloroprocaine continuous
      thoracic epidural analgesia for management of postthoracotomy pain in infants.
AB  - INTRODUCTION: Continuous thoracic epidural analgesia is useful in the management
      of infants following thoracotomy. Concerns about drug accumulation and toxicity
      limit the amount of amide local anesthetics that can be delivered. Continuous
      epidural infusions of the ester local anesthetic chloroprocaine result in little
      drug accumulation allowing for higher infusion rates. We retrospectively compared
      patients managed with 1.5% 2- chloroprocaine or 0.1% ropivacaine epidural
      infusions to determine if the increased infusion rate resulted in similar or
      improved analgesia. METHODS: This retrospective cohort comparison consisted of
      full term infants 6 months or younger who underwent thoracotomy for congenital
      lung lesion resection. Patients were included if they were managed with either a
      1.5% 2-chloroprocaine (Group C) (n = 26) or 0.1% ropivacaine (Group R) (n = 28)
      infusion administered through a caudally placed thoracic epidural catheter. The
      primary outcome was morphine administration at 0-24 h. RESULTS: Patients were
      similar in age, weight, length of stay, epidural location and duration. There was
      weak evidence for a difference in morphine use in the first 24 h in Group C
      compared to Group R (P = 0.08) but no difference 24-48 h. Group C was more
      commonly managed with ketorolac at 0-24 h (P = 0.03) and 24-48 h (P =< 0.01).
      DISCUSSION: The use of 2-chloroprocaine for continuous epidural infusion in
      infants following thoracotomy was not inferior to ropivacaine and there was weak
      evidence for a reduction in opioid consumption in the first 24 h postoperatively.
      However, the 2-chloroprocaine group was more likely to receive ketorolac.

PMID- 26306546
TI  - Dietary changes in migrant adolescents with increasing length of stay in
      Australia and associated risk of wheeze--a retrospective, cross sectional study.
AB  - BACKGROUND: Recent studies have reported that asthma prevalence increases on
      migration to Australia. We hypothesised that changes in dietary intake contribute
      to this phenomenon. The aim of this study was to assess dietary intake in
      relation to migration status, length of stay in Australia and the association
      with self-reported wheeze. METHODS: Students (n = 144) in a multicultural high
      school in Western Sydney completed the asthma symptoms ISAAC video questionnaire
      (AVQ3.0), spirometry and allergy skin prick tests. A dietitian administered
      a'Food Frequency' and 'Food Habits' questionnaire and a dietary history
      interview. RESULTS: Students who spoke a language other than English, consumed a
      traditional or mixed dietary pattern, with lower consumption of saturated fat,
      compared to students who spoke English only. Saturated fat intake increased and
      fibre intake decreased with length of time in Australia. Intake of foods high in
      saturated or trans fatty acids were positively associated with length of stay in
      Australia. No associations between nutrient intake or whole food intake and self
      reported wheeze were observed. CONCLUSION: As time progressed, dietary intake of
      immigrant children changed. While this was not associated with the development of
      wheeze in the students in this cohort, these changes are likely to have negative
      health consequences.

PMID- 26306548
TI  - Relationship between bone mineral density, its associated physiological factors,
      and tooth loss in postmenopausal Korean women.
AB  - BACKGROUND: Previous studies have proposed a relationship between bone mineral
      density (BMD) and oral health. However, the relationship between BMD and tooth
      loss in female individuals is not yet well understood. Therefore, the aim of this
      study was to assess the association between BMD, including its related
      physiological factors, and tooth loss among postmenopausal women in Korea.
      METHODS: A total of 3,992 postmenopausal women aged 50 years or above were
      selected from the Fourth and Fifth Korea National Health and Nutrition
      Examination Surveys, which were cross-sectional in design and conducted from 2008
      to 2011. The participants' BMD and number of teeth were assessed by radiologists
      and dentists. Socioeconomic characteristics and female-related physiological
      factors, including menarche age, duration of menopause, number of pregnancies,
      age at first child's birth, and duration of oral contraceptive or female hormone
      use, were surveyed. RESULTS: Participants who had lower BMD had significantly
      fewer teeth (p < 0.001). Female-related physiological factors, including the
      duration of menopause, number of pregnancies, age at first child's birth,
      duration of oral contraceptive or female hormone use, and calcium intake level,
      showed a significant relationship with the number of teeth. Using multiple
      regression analysis, BMD, duration of menopause, age at first child's birth, and
      duration of female hormone use significantly influenced the number of teeth.
      CONCLUSIONS: BMD and its related physiological factors in female individuals
      showed a significant relationship with the number of teeth in postmenopausal
      Korean women, implicating osteoporosis as a risk factor for tooth loss in
      postmenopausal women.

PMID- 26306547
TI  - Rasch-Transformed Total Neuropathy Score clinical version (RT-TNSc((c)) ) in
      patients with chemotherapy-induced peripheral neuropathy.
AB  - Composite scales such as the Total Neuropathy Score clinical version (TNSc((c)) )
      have been widely used to measure neurological impairment in a standardized manner
      but they have been criticized due to their ordinal setting having no fixed unit.
      This study aims to improve impairment assessment in patients with chemotherapy
      induced peripheral neuropathy (CIPN) by subjecting TNSc((c)) records to Rasch
      analyses. In particular, we wanted to investigate the influence of factors
      affecting the use of the TNSc((c)) in clinical practice. TNSc((c)) has 7 domains
      (sensory, motor, autonomic, pin-prick, vibration, strength, and deep tendon
      reflexes [DTR]) each being scored 0-4. Data obtained in 281 patients with stable
      CIPN were subjected to Rasch analyses to determine the fit to the model. The
      TNSc((c)) did not meet Rasch model's expectations primarily because of misfit
      statistics in autonomic and DTR domains. Removing these two, acceptable model fit
      and uni-dimensionality were obtained. However, disordered thresholds (vibration
      and strength) and item bias (mainly cultural) were still seen, but these findings
      were kept to balance the assessment range of the Rasch-Transformed TNSc((c)) (RT
      TNSc((c)) ). Acceptable reliability findings were also obtained. A 5-domains RT
      TNSc((c)) may be a more proper assessment tool in patients with CIPN. Future
      studies are needed to examine its responsive properties. 

PMID- 26306549
TI  - Planning for ex situ conservation in the face of uncertainty.
AB  - Ex situ conservation strategies for threatened species often require long-term
      commitment and financial investment to achieve management objectives. We present
      a framework that considers the decision to adopt ex situ management for a target
      species as the end point of several linked decisions. We used a decision tree to
      intuitively represent the logical sequence of decision making. The first decision
      is to identify the specific management actions most likely to achieve the
      fundamental objectives of the recovery plan, with or without the use of ex-situ
      populations. Once this decision has been made, one decides whether to establish
      an ex situ population, accounting for the probability of success in the initial
      phase of the recovery plan, for example, the probability of successful breeding
      in captivity. Approaching these decisions in the reverse order (attempting to
      establish an ex situ population before its purpose is clearly defined) can lead
      to a poor allocation of resources, because it may restrict the range of available
      decisions in the second stage. We applied our decision framework to the recovery
      program for the threatened spotted tree frog (Litoria spenceri) of southeastern
      Australia. Across a range of possible management actions, only those including ex
      situ management were expected to provide >50% probability of the species'
      persistence, but these actions cost more than use of in situ alternatives only.
      The expected benefits of ex situ actions were predicted to be offset by
      additional uncertainty and stochasticity associated with establishing and
      maintaining ex situ populations. Naively implementing ex situ conservation
      strategies can lead to inefficient management. Our framework may help managers
      explicitly evaluate objectives, management options, and the probability of
      success prior to establishing a captive colony of any given species.

PMID- 26306551
TI  - A highly photoreflective and heat-insulating alumina film composed of stacked
      mesoporous layers in hierarchical structure.
AB  - An alumina film with highly photoreflective and heat-insulating properties can be
      simply synthesized using a sol of fibrous boehmite with an additive. The
      entangled fibers bring about mesopores among them and form stacked 2D nonwoven
      like nanosheets. The porosity and the layered structure of alumina accompanying
      the heat resistivity provide the upper properties that are usually difficult to
      realize simultaneously. 

PMID- 26306550
TI  - Transposase interaction with the beta sliding clamp: effects on insertion
      sequence proliferation and transposition rate.
AB  - Insertion sequences (ISs) are ubiquitous and abundant mobile genetic elements in
      prokaryotic genomes. ISs often encode only one protein, the transposase, which
      catalyzes their transposition. Recent studies have shown that transposases of
      many different IS families interact with the beta sliding clamp, a DNA
      replication factor of the host. However, it was unclear to what extent this
      interaction limits or favors the ability of ISs to colonize a chromosome from a
      phylogenetically-distant organism, or if the strength of this interaction affects
      the transposition rate. Here we describe the proliferation of a member of the
      IS1634 family in Acidiphilium over ~600 generations of cultured growth. We
      demonstrate that the purified transposase binds to the beta sliding clamp of
      Acidiphilium, Leptospirillum and E. coli. Further, we also demonstrate that the
      Acidiphilium IS1634 transposase binds to the archaeal sliding clamp (PCNA) from
      Methanosarcina, and that the transposase encoded by Methanosarcina IS1634 binds
      to Acidiphilium beta. Finally, we demonstrate that increasing the strength of the
      interaction between beta and transposase results in a higher transposition rate
      in vivo. Our results suggest that the interaction could determine the potential
      of ISs to be mobilized in bacterial populations and also their ability to
      proliferate within chromosomes. 

PMID- 26306552
TI  - Prevalence of older people with intellectual disability in Sweden: a spatial
      epidemiological analysis.
AB  - BACKGROUND: The expected increase in longevity of individuals with intellectual
      disabilities (ID) in many countries of the world is a direct result of medical
      and social advances, which have also extended the longevity of the general
      population. It is important to assess the need for social services for people
      with ID across different administrative levels to ensure sufficient resources are
      allocated to where they are most needed. This study estimates the annual
      prevalence of older people with ID from 2004 to 2012 and in different counties
      and municipalities in Sweden, by sex and age group; identifies proxy indicators
      related to the care of older people with ID in different counties in 2012 in
      Sweden and analyses the spatial distribution and clustering of municipalities
      with a high prevalence of older people with ID. METHODS: Individuals with ID were
      identified through the national register based on the Swedish Act concerning
      Support and Service for Persons with Certain Functional Impairments (the LSS act)
      and the national death register. This study focuses on older individuals aged 55+
      during the period of 2004-2012. The estimated prevalence was calculated at the
      county and municipality level and plotted on a municipality-level map. Moran's I
      statistics was used to identify any spatial clustering of municipalities with a
      large number of individuals with ID. RESULTS: The prevalence of ID among older
      individuals aged 55+ in Sweden increased from 2004 to 2012. The prevalence was
      consistently higher among men, and the gender gap increased slightly in recent
      years. Age-specific prevalence estimates showed ID to be higher in younger age
      groups, and the gender gap decreased in older age groups. The prevalence was
      higher in northern counties in Sweden (over 500 individuals per 100 000
      population aged 55+). Higher prevalence areas were clustered in northern
      municipalities, whereas municipalities with high prevalence of older individuals
      with ID in the middle and southern regions of Sweden demonstrated a more
      widespread distribution. CONCLUSIONS: The existence of clusters of counties with
      a high prevalence of older individuals with ID necessitates further assessment of
      how resources have been allocated to different counties and municipalities in
      Sweden. Investigations of the quality of social services provided to individuals
      with ID across different counties in Sweden are warranted. It is important to
      ensure that high quality supports are being provided to older individuals with ID
      in order to grant them the same right to healthy ageing as their counterparts
      living without ID throughout their life course.

PMID- 26306553
TI  - Sol-gel synthesis of quaternary (P2O5)55-(CaO)25-(Na2O)(20-x)-(TiO2) x
      bioresorbable glasses for bone tissue engineering applications (x = 0, 5, 10, or
      15).
AB  - In the present study, we report a new and facile sol-gel synthesis of phosphate
      based glasses with the general formula of (P2O5)55-(CaO)25-(Na2O)(20-x)-(TiO2) x
      , where x = 0, 5, 10 or 15, for bone tissue engineering applications. The sol-gel
      synthesis method allows greater control over glass morphology at relatively low
      processing temperature (200  degrees C) in comparison with phosphate-based melt
      derived glasses (~1000  degrees C). The glasses were analyzed using several
      characterization techniques, including x-ray diffraction (XRD), (31)P magic angle
      spinning nuclear magnetic resonance ((31)P MAS-NMR), Fourier transform infrared
      (FTIR) spectroscopy and energy-dispersive x-ray (EDX) spectroscopy, which
      confirmed the amorphous and glassy nature of the prepared samples. Degradation
      was assessed by measuring the ion release and pH change of the storage medium.
      Cytocompatibility was also confirmed by culturing osteoblast-like osteosarcoma
      cell line MG-63 on the glass microparticles over a seven-day period. Cell
      attachment to the particles was imaged using scanning electron microscopy (SEM)
      and confocal laser scanning microscopy (CLSM). The results revealed the potential
      of phosphate-based sol-gel derived glasses containing 5 or 10 mol% TiO2, with
      high surface area, ideal dissolution rate for cell attachment and easily
      metabolized dissolution products, for bone tissue engineering applications. 

PMID- 26306554
TI  - Insect herbivory elicits genome-wide alternative splicing responses in Nicotiana
      attenuata.
AB  - Changes in gene expression and alternative splicing (AS) are involved in many
      responses to abiotic and biotic stresses in eukaryotic organisms. In response to
      attack and oviposition by insect herbivores, plants elicit rapid changes in gene
      expression which are essential for the activation of plant defenses; however, the
      herbivory-induced changes in AS remain unstudied. Using mRNA sequencing, we
      performed a genome-wide analysis on tobacco hornworm (Manduca sexta) feeding
      induced AS in both leaves and roots of Nicotiana attenuata. Feeding by M. sexta
      for 5 h reduced total AS events by 7.3% in leaves but increased them in roots by
      8.0% and significantly changed AS patterns in leaves and roots of existing AS
      genes. Feeding by M. sexta also resulted in increased (in roots) and decreased
      (in leaves) transcript levels of the serine/arginine-rich (SR) proteins that are
      involved in the AS machinery of plants and induced changes in SR gene expression
      that were jasmonic acid (JA)-independent in leaves but JA-dependent in roots.
      Changes in AS and gene expression elicited by M. sexta feeding were regulated
      independently in both tissues. This study provides genome-wide evidence that
      insect herbivory induces changes not only in the levels of gene expression but
      also in their splicing, which might contribute to defense against and/or
      tolerance of herbivory. 

PMID- 26306555
TI  - Toward a Metacognitive Account of Cognitive Offloading.
AB  - Individuals frequently make use of the body and environment when engaged in a
      cognitive task. For example, individuals will often spontaneously physically
      rotate when faced with rotated objects, such as an array of words, to putatively
      offload the performance costs associated with stimulus rotation. We looked to
      further examine this idea by independently manipulating the costs associated with
      both word rotation and array frame rotation. Surprisingly, we found that
      individuals' patterns of spontaneous physical rotations did not follow patterns
      of performance costs or benefits associated with being physically rotated,
      findings difficult to reconcile with existing theories of strategy selection
      involving external resources. Individuals' subjective ratings of perceived
      benefits, rather, provided an excellent match to the patterns of physical
      rotations, suggesting that the critical variable when deciding on-the-fly whether
      to incorporate an external resource is the participant's metacognitive beliefs
      regarding expected performance or the effort required for each approach (i.e.,
      internal vs. internal + external). Implications for metacognition's future in
      theories of cognitive offloading are discussed.

PMID- 26306556
TI  - Site-directed, on-surface assembly of DNA nanostructures.
AB  - Two-dimensional DNA lattices have been assembled from DNA double-crossover (DX)
      motifs on DNA-encoded surfaces in a site-specific manner. The lattices contained
      two types of single-stranded protruding arms pointing into opposite directions of
      the plane. One type of these protruding arms served to anchor the DNA lattice on
      the solid support through specific hybridization with surface-bound,
      complementary capture oligomers. The other type of arms allowed for further
      attachment of DNA-tethered probe molecules on the opposite side of the lattices
      exposed to the solution. Site-specific lattice assembly and attachment of
      fluorophore-labeled oligonucleotides and DNA-protein conjugates was demonstrated
      using DNA microarrays on flat, transparent mica substrates. Owing to their
      programmable orientation and addressability over a broad dynamic range from the
      nanometer to the millimeter length scale, such supramolecular architecture might
      be used for presenting biomolecules on surfaces, for instance, in biosensor
      applications. 

PMID- 26306557
TI  - African Perspectives.

PMID- 26306558
TI  - Multilevel analysis of individual and community level factors associated with
      institutional delivery in Ethiopia.
AB  - BACKGROUND: Improving maternal health is one of the eight millennium development
      goals to reduce maternal mortality (MM) by three quarters between 1990 and 2015.
      Institutional delivery is considered to be the most critical intervention in
      reducing MM and ensuring safe motherhood. However, the level of maternal
      morbidity and mortality in Ethiopia are among the highest in the world and the
      proportion of births occurring at health facilities is very low. This study
      examined the individual and community level factors associated with institutional
      delivery in Ethiopia. METHODS: Data from the 2011 Ethiopian demographic and
      health survey were used to identify individual and community level factors
      associated with institutional delivery among women who had a live birth during
      the 5 years preceding the survey. Taking into account the nested structure of the
      data, multilevel logistic regression analysis has been employed to a nationally
      representative sample of 7757 women nested with in 595 communities. RESULTS: At
      the individual level; higher educational level of the women (AOR = 3.60; 95% CI
      2.491-5.214), women from richest households (AOR = 1.74; 95% CI 1.143-2.648) and
      increased ante natal care attendance (AOR = 4.43; 95% CI 3.405-5.751) were
      associated with institutional delivery. Additionally, at the community level;
      urban residence (AOR = 4.74; 95% CI 3.196-7.039), residing in communities with
      high proportion of educated women (AOR = 1.71; 95% CI 1.256-2.319) and residing
      in communities with high ANC utilization rate (AOR = 1.55; 95% CI 1.132-2.127)
      had a significant effect on institutional delivery. Also region and distance to
      health facility showed significant association with institutional delivery. The
      random effects showed that the variation in institutional delivery service
      utilization between communities was statistically significant. CONCLUSION: Both
      individual and community level factors are associated with institutional delivery
      service uptake. As a result, further research is needed to better understand why
      these factors may affect institutional delivery.

PMID- 26306559
TI  - Dietary carbohydrate and lipid source affect cholesterol metabolism of European
      sea bass (Dicentrarchus labrax) juveniles.
AB  - Plant feedstuffs (PF) are rich in carbohydrates, which may interact with lipid
      metabolism. Thus, when considering dietary replacement of fishery by-products
      with PF, knowledge is needed on how dietary lipid source (LS) and carbohydrates
      affect lipid metabolism and other metabolic pathways. For that purpose, a 73-d
      growth trial was performed with European sea bass juveniles (IBW 74 g) fed four
      diets differing in LS (fish oil (FO) or a blend of vegetable oils (VO)) and
      carbohydrate content (0 % (CH-) or 20 % (CH+) gelatinised starch). At the end of
      the trial no differences among diets were observed on growth and feed
      utilisation. Protein efficiency ratio was, however, higher in the CH+ groups.
      Muscle and liver fatty acid profiles reflected the dietary LS. Dietary
      carbohydrate promoted higher plasma cholesterol and phospholipids (PL), whole
      body and hepatic (mainly 16 : 0) lipids and increased muscular and hepatic
      glycogen. Except for PL, which were higher in the FO groups, no major alterations
      between FO and VO groups were observed on plasma metabolites (glucose, TAG,
      cholesterol, PL), liver and muscle glycogen, and lipid and cholesterol contents.
      Activities of glucose-6-phosphate dehydrogenase and malic enzyme - lipogenesis
      related enzymes - increased with carbohydrate intake. Hepatic expression of genes
      involved in cholesterol metabolism was up-regulated with carbohydrate (HMGCR and
      CYP3A27) and VO (HMGCR and CYP51A1) intake. No dietary regulation of long-chain
      PUFA biosynthesis at the transcriptional level was observed. Overall, very few
      interactions between dietary carbohydrates and LS were observed. However,
      important insights on the direct relation between dietary carbohydrate and the
      cholesterol biosynthetic pathway in European sea bass were demonstrated. 

PMID- 26306561
TI  - Barley domestication: the end of a central dogma?
AB  - Genomic analysis of barley paints a picture of diffuse origins of this crop, with
      different regional wild populations contributing putative adaptive variations. 

PMID- 26306560
TI  - Stromal ING1 expression induces a secretory phenotype and correlates with breast
      cancer patient survival.
AB  - BACKGROUND: Previous studies have established that levels of the Inhibitor of
      Growth 1(ING1) tumor suppressor are reduced in a significant proportion of
      different cancer types. Here we analyzed levels of ING1 in breast cancer patients
      to determine its prognostic significance as a biomarker for breast cancer
      prognosis. METHODS: We used automated quantitative analysis (AQUA) to determine
      the levels of ING1 in the tumor associated stromal cells of 462 breast cancer
      samples. To better understand how high ING1 levels affect nearby epithelium, we
      measured the levels of cytokines and secreted matrix metalloproteases (MMPs),
      using an ELISA based assay in mammary fibroblasts overexpressing ING1. These
      cells were also used in a 3-dimensional co-culture with MCF7 cells to determine
      the effect of released MMPs and other cytokines on growing colonies. RESULTS: We
      find that high levels of ING1 in stroma are associated with tumor grade (p =
      0.001) and size (p = 0.02), and inversely associated with patient survival (p =
      0.0001) in luminal, but not in non-luminal cancers, suggesting that high stromal
      ING1 promotes cancer development. In this group of patients ING1 could also
      predict patient survival and act as a biomarker (HR = 2.125). While ING1
      increased or decreased the expression of different cytokines, ING1 also increased
      the levels of MMP1, MMP3 and MMP10 by 5-8 fold, and concomitantly decreased
      levels of the tissue inhibitors of metalloproteases TIMP2, TIMP3 and TIMP4 by 1.5
      3.3 fold, resulting in significant increases in MMP activity as determined by
      zymography. Co-culturing of MCF7 cells with stromal cells expressing ING1 in 3
      dimensional organoid cultures suggested that MCF7 colonies were less well
      defined, suggesting that secreted MMPs might promote migration. CONCLUSION: These
      data indicate that stromal ING1 expression can predict the survival of patients
      with luminal breast cancer. High levels of ING1 in stromal cells can promote the
      development of breast cancer through increased expression and release of MMPs and
      down regulation of TIMPs, which may be an underlying mechanism of reduced patient
      survival.

PMID- 26306562
TI  - Sequential molecularly targeted drug therapy including axitinib for a patient
      with end-stage renal failure and metastatic renal cell carcinoma.
AB  - A 62-year-old male patient with end-stage renal disease and metastatic renal cell
      carcinoma (RCC) was referred to our hospital. Sequential targeted therapy
      consisting of sorafenib, sunitinib, and everolimus was administered, but the
      patient's disease gradually progressed. Axitinib was subsequently administered at
      a decreased dose of 6 mg/day for 2 weeks, after which the dose was escalated to
      10 mg/day. Axitinib therapy was maintained for a total of 6 months without severe
      adverse effects. Sequential molecularly targeted drug therapy including axitinib,
      with careful monitoring, is one possible treatment option for patients with
      metastatic RCC with renal impairment. 

PMID- 26306563
TI  - Patient safety education and baccalaureate nursing students' patient safety
      competency: A cross-sectional study.
AB  - This cross-sectional study examines baccalaureate nursing programs in South Korea
      to determine how and to what extent patient safety education was delivered, and
      to assess nursing students' patient safety competency. The Quality and Safety
      Education for Nurses (QSEN) student evaluation survey and a Patient Safety
      Competency Self-Evaluation tool were used. We distributed 234 surveys to senior
      students in four nursing schools; 206 (88%) students responded to the survey. The
      majority of students (81.6%) reported that they had received patient safety
      education during coursework. Patient safety education was delivered primarily by
      lecture rather than during laboratory or simulation sessions. The degree of
      coverage of QSEN competency and the students' self-reported competency in total
      and attitude scores showed statistical differences among nursing schools.
      Students' attitude score was significantly higher than skill and knowledge. Our
      results confirm the need to revise the nursing curriculum and to use various
      teaching methods to deliver patient safety education more comprehensively and
      effectively. Furthermore, there is a need to develop an integrated approach to
      ensuring students' balanced competency. 

PMID- 26306564
TI  - Heart rate and ischemic stroke: the REasons for Geographic And Racial Differences
      in Stroke (REGARDS) study.
AB  - BACKGROUND: The association between resting heart rate and ischemic stroke
      remains unclear. AIM: To examine the association between resting heart rate and
      ischemic stroke. METHODS: A total of 24 730 participants (mean age: 64 +/- 9.3
      years; 59% women; 41% blacks) from the REasons for Geographic And Racial
      Differences in Stroke (REGARDS) study who were free of stroke at the time of
      enrollment (2003-2007) were included in this analysis. Resting heart rate was
      determined from baseline electrocardiogram data. Heart rate was examined as a
      continuous variable per 10 bpm increase and also as a categorical variable using
      tertiles ( <61 bpm, 61 to 70 bpm, and >70 bpm). First-time ischemic stroke events
      were identified during follow-up and adjudicated by physician review. RESULTS:
      Over a median follow-up of 7.6 years, a total of 646 ischemic strokes occurred.
      In a Cox regression model adjusted for socio-demographics, cardiovascular risk
      factors, and potential confounders, each 10 bpm increase in heart rate was
      associated with a 10% increase in the risk of ischemic stroke (hazard ratio =
      1.10, 95% confidence interval = 1.02, 1.18). In the categorical model, an
      increased risk of ischemic stroke was observed for heart rates in the middle
      (hazard ratio = 1.29, 95% confidence interval = 1.06, 1.57) and upper (hazard
      ratio = 1.37, 95% confidence interval = 1.12, 1.67) tertiles compared with the
      lower tertile. The results were consistent when the analysis was stratified by
      age, gender, race, exercise habits, hypertension, and coronary heart disease.
      CONCLUSION: In REGARDS, high resting heart rates were associated with an
      increased risk of ischemic stroke compared with low heart rates. Further research
      is needed to examine whether interventions aimed to reduce heart rate decrease
      stroke risk.

PMID- 26306565
TI  - New radiotherapy techniques do not reduce the need for nutrition intervention in
      patients with head and neck cancer.
AB  - BACKGROUND/OBJECTIVES: Since 2007, our institution has used validated guidelines
      for the insertion of proactive gastrostomy feeding tubes in patients with head
      and neck cancer. Helical intensity-modulated radiotherapy (H-IMRT) delivered by
      Tomotherapy, is an advanced radiotherapy technique introduced at our centre in
      2010. This form of therapy reduces long-term treatment-related toxicity to normal
      tissues. The aim of this study is to compare weight change and need for tube
      feeding following H-IMRT (n=53) with patients that would have previously been
      treated with three-dimensional conformal radiotherapy (n=134). SUBJECTS/METHODS:
      Patients with head and neck cancer assessed as high nutritional risk with
      recommendation for proactive gastrostomy were identified from cohorts from 2007
      to 2008 and 2010 to 2011. Retrospective data were collected on clinical factors,
      weight change from baseline to completion of treatment, incidence of severe
      weight loss (? 10%) and tube feeding. Statistical analyses to compare outcomes
      between the two treatments included chi(2)-test, Fisher's exact and two-sample
      Wilcoxon tests (P<0.05). RESULTS: The H-IMRT cohort had higher proportions of
      patients with definitive chemoradiotherapy (P=0.032) and more advanced N stage
      (P<0.001). Nutrition outcomes were not significantly different between H-IMRT and
      conformal radiotherapy, respectively: need for proactive gastrostomy (n=49, 92%
      versus n=115, 86%, P=0.213), median percentage weight change (-7.2% versus -7.3%,
      P=0.573) and severe weight loss incidence (28% versus 27%, P=0.843). CONCLUSIONS:
      Both groups had median weight loss >5% and high incidences of tube feeding and
      severe weight loss. Nutrition intervention remains critical in this patient
      population, despite advances in radiotherapy techniques, and no changes to
      current management are recommended.

PMID- 26306566
TI  - Effects of 6-month supplementation with beta-hydroxy-beta-methylbutyrate,
      glutamine and arginine on vascular endothelial function of older adults.
AB  - BACKGROUND/OBJECTIVES: Vascular endothelial function declines with advancing age,
      due in part to increased oxidative stress and inflammation, and this age-related
      vascular dysfunction has been identified as an independent risk factor for
      cardiovascular diseases. This double-blind, placebo-controlled trial investigated
      the effects of a dietary supplement containing beta-hydroxy-beta-methylbutyrate
      (HMB), glutamine and arginine on endothelial-dependent vasodilation of older
      adults. SUBJECTS/METHODS: A total of 31 community-dwelling men and women aged 65
      87 years were randomly assigned to two groups. The treatment group received two
      doses of the supplement daily (totaling 3 g HMB, 14 g glutamine and 14 g
      arginine) for 6 months, whereas the control group received an isocaloric placebo.
      At baseline and week 24, vascular endothelial function was measured by flow
      mediated dilation of the brachial artery, and fasting blood samples were obtained
      to measure high-sensitivity C-reactive protein (hsCRP) and tumor necrosis factor
      alpha (TNF-alpha). RESULTS: Paired sample t-tests revealed a 27% increase in flow
      mediated dilation among the treatment group (P=0.003), whereas no change was
      observed in the placebo group (P=0.651). Repeated-measures analysis of variance
      verified a significant time by group interaction (P=0.038). Although no
      significant changes were observed for hsCRP or TNF-alpha, a trend was observed
      for increasing hsCRP among the placebo group only (P=0.059). CONCLUSIONS: These
      results suggest that dietary supplementation of HMB, glutamine and arginine may
      favorably affect vascular endothelial function in older adults. Additional
      studies are needed to elucidate whether reduced inflammation or other mechanisms
      may underlie the benefits of supplementation.

PMID- 26306567
TI  - Established enteral nutrition pathway in a severe acute pancreatitis patient with
      duodenum fistula: a case report.
AB  - Enteral feeding is the preferred way to provide nutritional support in patients
      with high nutritional risk but relatively normal gastrointestinal function; thus,
      establishing a safe and a reliable pathway of enteral nutrition (EN) is of great
      importance. There are many techniques for placing the feeding tube, such as blind
      placement at bedside, assisting by fluoroscopy and endoscopy, surgical and so on.
      Despite these variable techniques, it is still difficult to obtain the pathway
      for EN in some specific patients. Here, we present a recent case of infected
      pancreatic/peripancreatic necrosis complicated by a duodenal enteric fistula in
      whom we establish the feeding pathway extraordinarily. Briefly, after several
      failed attempts of placing the nasojejunal feeding tube, a jejunal feeding tube
      was placed percutaneously guided by computed tomography, and EN was successfully
      applied thereafter. With the implementation of EN, duodenal fistula healed
      without surgical intervention. As EN is pivotal for the recovery of duodenal
      fistula, this novel approach could be beneficial in selected patients. 

PMID- 26306568
TI  - External Fixation: Principles and Applications.
AB  - The modularity and ease of application of modern external fixation has expanded
      its potential use in the management of fractures and other musculoskeletal
      conditions. In fracture care, it can be used for provisional and definitive
      fixation. Short-term provisional applications include "damage control" and
      periarticular fracture fixation. The risk:benefit ratio of added stability needs
      to be assessed with each fixator. Soft-tissue management is critical during pin
      insertion to lessen the risk of loosening and infection. Although provisional
      fixation is safe for early conversion to definitive fixation, several factors
      affect the timing of definitive surgery, including the initial injury, external
      fixator stability, infection, and the physiologic state of the patient. 

PMID- 26306569
TI  - Language and literacy in children with benign epilepsy with centrotemporal
      spikes.

PMID- 26306570
TI  - JAM-A regulates cortical dynein localization through Cdc42 to control planar
      spindle orientation during mitosis.
AB  - Planar spindle orientation in polarized epithelial cells depends on the precise
      localization of the dynein-dynactin motor protein complex at the lateral cortex.
      The contribution of cell adhesion molecules to the cortical localization of the
      dynein-dynactin complex is poorly understood. Here we find that junctional
      adhesion molecule-A (JAM-A) regulates the planar orientation of the mitotic
      spindle during epithelial morphogenesis. During mitosis, JAM-A triggers a
      transient activation of Cdc42 and PI(3)K, generates a gradient of PtdIns(3,4,5)P3
      at the cortex and regulates the formation of the cortical actin cytoskeleton. In
      the absence of functional JAM-A, dynactin localization at the cortex is reduced,
      the mitotic spindle apparatus is misaligned and epithelial morphogenesis in three
      dimensional culture is compromised. Our findings indicate that a PI(3)K- and
      cortical F-actin-dependent pathway of planar spindle orientation operates in
      polarized epithelial cells to regulate epithelial morphogenesis, and we identify
      JAM-A as a junctional regulator of this pathway. 

PMID- 26306572
TI  - Rapid Determination of Clenbuterol in Pork by Direct Immersion Solid-Phase
      Microextraction Coupled with Gas Chromatography-Mass Spectrometry.
AB  - Direct immersion solid-phase microextraction (DI-SPME) coupled with gas
      chromatography-mass spectrometry (GC-MS) was developed for rapid analysis of
      clenbuterol in pork for the first time. In this work, a low-cost homemade 44 um
      polydimethylsiloxane (PDMS) SPME fiber was employed to extract clenbuterol in
      pork. After extraction, derivatization was performed by suspending the fiber in
      the headspace of the 2 mL sample vial saturated with a vapor of 100 uL
      hexamethyldisilazane. Lastly, the fiber was directly introduced to GC-MS for
      analysis. All parameters that influenced absorption (extraction time),
      derivatization (derivatization reagent, time and temperature) and desorption
      (desorption time) were optimized. Under optimized conditions, the method offered
      a wide linear range (10-1000 ng g(-1)) and a low detection limit (3.6 ng g(-1)).
      Finally, the method was successfully applied in the analysis of pork from the
      market, and recoveries of the method for spiked pork were 97.4-105.7%. Compared
      with the traditional solvent extraction method, the proposed method was much
      cheaper and fast. 

PMID- 26306571
TI  - Comparison of clinical and radiologic treatment outcomes of Kienbock's disease.
AB  - PURPOSE: The clinical outcomes of scaphotrapeziotrapezoid (STT) arthrodesis were
      compared to radial shortening osteotomy (RSO) to determine if any of the
      treatment methods was superior. The impact of RSO and vascularized bone grafts
      (VBG) on disease progression were measured based on X-rays to evaluate if a
      difference in Kienbock's disease (KD) progression exists. METHODS: Out of 98
      consecutive patients treated between 1991 and 2013, 46 had STT arthrodesis, 21
      had RSO, 7 had VBG, and 3 had VBG and RSO. Patients treated with STT arthrodesis
      were compared to RSO regarding post-operative range of motion (ROM), wrist pain
      on the Numeric Rating Scale (NRS), grip strength, duration of incapacity for
      work, the Disabilities of the Arm, Shoulder, and Hand (DASH), and the Modified
      Mayo Wrist scores (MMWS). Radiographic assessment (Nattrass index, radioscaphoid
      angle, and Stahl index) was performed to determine disease progression following
      RSO or VBG. Baseline patient characteristics were comparable in all treatment
      groups. RESULTS: There were no significant differences in post-operative ROM,
      wrist pain, grip strength, duration of incapacity, DASH score, or MMWS score
      following STT arthrodesis (n = 27) or RSO (n = 14). The Stahl index, the Nattrass
      index, and the radioscaphoid angle suggested disease progression following RSO (n
      = 14) and/or VBG (n = 6) although the changes were not significant. CONCLUSIONS:
      The study failed to demonstrate clinically relevant differences between STT
      arthrodesis compared to RSO. No evidence was found that decompression or
      revascularization, or the combination of the two, can reverse or halt the course
      of the disease. LEVEL OF EVIDENCE: Therapy, level III, retrospective comparative
      study with prospectively collected data.

PMID- 26306573
TI  - Development and Validation of HPLC and HPTLC Methods for Determination of
      Cefoperazone and Its Related Impurities.
AB  - Validated sensitive and highly selective methods were developed for the
      quantitative determination of cefoperazone sodium (CEF) in the presence of its
      reported impurities; 7-aminocephalosporanic acid (7-ACA) and 5-mercapto-1-methyl
      tetrazole (5-MER). Method A is high-performance liquid chromatography (HPLC),
      where the mixture of CEF and the reported impurities; 7-ACA and 5-MER were
      separated on a C8 column (5 um ps, 250 mm * 4.6 i.d.) using methanol:0.05 M
      KH2PO4 buffer (22.5:77.5 v/v, pH 7.5) as a mobile phase. The three components
      were detected at 254 nm with a concentration range of 10-90 ug mL(-1) and the
      mean percentage recovery 99.67% (SD 1.465). Method B is high-performance thin
      layer chromatography (HPTLC), where the mixture of CEF and the reported
      impurities were separated on silica gel HPTLC F254 plates using
      (acetone:methanol:ethyl acetate:2% sodium lauryl sulfate:glacial acetic acid)
      (3:2:3:0.8:0.2, by volume) as a developing system and scanning at 254 nm over a
      concentration range of 1-10 ug per band with the mean percentage recovery 99.95%
      (SD 1.335). The proposed methods were statistically compared with a reported HPLC
      method with no significant difference regarding accuracy and precision;
      indicating the ability of the proposed methods to be reliable and suitable for
      routine analysis of drug product. The proposed HPTLC method proved to be more
      sensitive, while the HPLC gave more reproducible results besides saving time. 

PMID- 26306574
TI  - Endophytic Fungus from Sinopodophyllum emodi (Wall.) Ying that Produces
      Podophyllotoxin.
AB  - The aryltetralin lactone podophyllotoxin, which exhibits pronounced
      antineoplastic activity, is used as the precursor of the following three clinical
      anticancer drugs: EtoposideTM, EtopophosTM and TeniposideTM. The natural
      occurrence of this arylnaphthalene lignan is scarce and unable to meet the ever
      rising demand in the medical industry. Thus, developing alternative sources for
      the production of podophyllotoxin is extremely urgent. This is the first report
      of the production of podophyllotoxin from endophytic Alternaria tenuissima
      isolated from Sinopodophyllum emodi (Wall.) Ying. The identification of
      podophyllotoxin was performed using high-performance liquid chromatography and
      liquid chromatography-mass spectrometry (MS)-MS and confirmed by comparison with
      authentic standards. 

PMID- 26306575
TI  - Proteomics in Argentina - limitations and future perspectives: A special emphasis
      on meat proteomics.
AB  - Argentina is one of the most relevant countries in Latin America, playing a major
      role in regional economics, culture and science. Over the last 80 years,
      Argentinean history has been characterized by several upward and downward phases
      that had major consequences on the development of science in the country and most
      recently on proteomics. In this article, we characterize the evolution of
      Proteomics sciences in Argentina over the last decade and a half. We describe the
      proteomics publication output of the country in the framework of the regional and
      international contexts, demonstrating that Argentina is solidly anchored in a
      regional context, showing results similar to other emergent and Latin American
      countries, albeit still far from the European, American or Australian realities.
      We also provide a case-study on the importance of Proteomics to a specific sector
      in the area of food science: the use of bacteria of technological interest,
      highlighting major achievements obtained by Argentinean proteomics scientists.
      Finally, we provide a general picture of the endeavors being undertaken by
      Argentinean Proteomics scientists and their international collaborators to
      promote the Proteomics-based research with the new generation of scientists and
      PhD students in both Argentina and other countries in the Southern cone. 

PMID- 26306577
TI  - Cardiovascular magnetic resonance assessment of the aortic valve stenosis: an in
      vivo and ex vivo study.
AB  - BACKGROUND: Aortic valve area (AVA) estimation in patients with aortic stenosis
      may be obtained using several methods. This study was undertaken to verify the
      cardiovascular magnetic resonance (CMR) planimetry of aortic stenosis by
      comparing the findings with invasive catheterization, transthoracic (TTE) as well
      as tranesophageal echocardiography (TEE) and anatomic CMR examination of autopsy
      specimens. METHODS: Our study was performed in eight patients with aortic valve
      stenosis. Aortic stenosis was determined by TTE and TEE as well as
      catheterization and CMR. Especially, after aortic valve replacement, the
      explanted aortic valves were examined again with CMR ex vivo model. RESULTS: The
      mean AVA determined in vivo by CMR was 0.75 +/- 0.09 cm(2) and ex vivo by CMR was
      0.65 +/- 0.09 cm(2) and was closely correlated (r = 0.91, p < 0.001). The mean
      absolute difference between AVA derived by CMR ex vivo and in vivo was -0.10 +/-
      0.04 cm(2). The mean AVA using TTE was 0.69 +/- 0.07 with a significant
      correlation between CMR ex vivo (r = 0.85, p < 0.007) and CMR in vivo (r = 0.86,
      p < 0.008). CMR ex vivo and in vivo had no significant correlation with AVA using
      Gorlin formula by invasive catheterization or using planimetry by TEE.
      CONCLUSION: In this small study using an ex vivo aortic valve stenosis model, the
      aortic valve area can be reliably planimetered by CMR in vivo and ex vivo with a
      well correlation between geometric AVA by CMR and the effective AVA calculated by
      TTE.

PMID- 26306576
TI  - Infectious hematopoietic necrosis virus (IHNV) persistence in Sockeye Salmon:
      influence on brain transcriptome and subsequent response to the viral mimic
      poly(I:C).
AB  - BACKGROUND: Sockeye Salmon are an iconic species widely distributed throughout
      the North Pacific. A devastating pathogen of Sockeye Salmon is infectious
      hematopoietic necrosis virus (IHNV, genus Novirhabdovirus, family Rhabdoviridae).
      It has been postulated that IHNV is maintained in salmon populations by
      persisting over the life of its host and/or by residing in natural reservoirs
      other than its susceptible hosts. Herein we demonstrate the presence of IHNV in
      the brain of Sockeye Salmon that survived an experimentally-induced outbreak,
      suggesting the presence of viral persistence in this susceptible species. To
      understand the viral persistent state in Sockeye Salmon we profiled the
      transcriptome to evaluate the host response in asymptomatic carriers and to
      determine what effects (if any) IHNV exposure may have on subsequent virus
      challenges. RESULTS: A laboratory disease model to simulate a natural IHNV
      outbreak in Sockeye Salmon resulted in over a third of the population incurring
      acute IHN disease and mortality during the first four months after initial
      exposure. Nine months post IHNV exposure, despite the absence of disease and
      mortality, a small percentage (<4 %) of the surviving population contained IHNV
      in brain. Transcriptome analysis in brain of asymptomatic virus carriers and
      survivors without virus exhibited distinct transcriptional profiles in comparison
      to naive fish. Characteristic for carriers was the up-regulation of genes
      involved in antibody production and antigen presentation. In both carriers and
      survivors a down-regulation of genes related to cholesterol biosynthesis,
      resembling an antiviral mechanism observed in higher vertebrates was revealed
      along with differences in nervous system development. Moreover, following
      challenge with poly(I:C), survivors and carriers displayed an elevated antiviral
      immune response in comparison to naive fish. CONCLUSIONS: IHN virus persistence
      was identified in Sockeye Salmon where it elicited a unique brain transcriptome
      profile suggesting an ongoing adaptive immune response. IHNV carriers remained
      uncompromised in mounting efficient innate antiviral responses when exposed to a
      viral mimic. The capacity of IHNV to reside in asymptomatic hosts supports a
      virus carrier hypothesis and if proven infectious, could have significant
      epidemiological consequences towards maintaining and spreading IHNV among
      susceptible host populations.

PMID- 26306578
TI  - Blood pressure lowering efficacy of dual alpha and beta blockers for primary
      hypertension.
AB  - BACKGROUND: Drugs with combined alpha and beta blocking activity are commonly
      prescribed to treat hypertension. However, the blood pressure (BP) lowering
      efficacy of this class of beta blockers has not been systematically reviewed and
      quantified. OBJECTIVES: To quantify the dose-related effects of various types of
      dual alpha and beta adrenergic receptor blockers (dual receptor blockers) on
      systolic and diastolic blood pressure versus placebo in patients with primary
      hypertension. SEARCH METHODS: We searched the Cochrane Hypertension Group
      Specialised Register, the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE, EMBASE and ClinicalTrials.gov for randomized controlled
      trials up to October 2014. The WHO International Clinical Trials Registry
      Platform (ICTRP) is searched for inclusion in the Group's Specialised Register.
      SELECTION CRITERIA: Randomized double blind placebo controlled parallel or cross
      over trials. Studies contained a beta blocker monotherapy arm with a fixed dose.
      Patients enrolled in the studies had primary hypertension at baseline. Duration
      of the studies was from three to 12 weeks. Drugs in this class of beta blockers
      are carvedilol, dilevalol and labetalol. DATA COLLECTION AND ANALYSIS: Two review
      authors (GW and AL) confirmed the inclusion of studies and extracted the data
      independently. RevMan 5.3 was used to synthesize data. MAIN RESULTS: We included
      eight studies examining the blood pressure lowering efficacy of carvedilol and
      labetalol in 1493 hypertensive patients. Five of the included studies were
      parallel design; three were cross-over design. The two largest included studies
      were unpublished carvedilol studies. The estimates of BP lowering effect
      (systolic BP/diastolic BP millimeters of mercury; SPB/DBP mm Hg) were -4 mm Hg
      (95% confidence intervals (CI) -6 to -2)/-3 mm Hg (95% CI -4 to -2) for
      carvedilol (>1000 subjects) and -10 mm Hg (95% CI -14 to -7)/-7 mm Hg (95% CI -9
      to -5) for labetalol (110 subjects). The effect of labetalol is likely to be
      exaggerated due to high risk of bias. Carvedilol, within the recommended dose
      range, did not show a significant dose response effect for SBP or DBP. Carvedilol
      had little or no effect on pulse pressure (-1 mm Hg) and did not change BP
      variability. Overall, once and twice the starting dose of carvedilol and
      labetalol lowered BP by -6 mm Hg (95% CI -7 to -4) /-4 mm Hg (95% CI -4 to -3)
      (low quality evidence) and lowered heart rate by five beats per minute (95% CI -6
      to -4) (low quality evidence). Five studies (N = 1412) reported withdrawal due to
      adverse effects; the risk ratio was 0.88 (95% CI 0.54 to 1.42) (moderate quality
      evidence). AUTHORS' CONCLUSIONS: This review provides low quality evidence that
      in patients with mild to moderate hypertension, dual receptor blockers lowered
      trough BP by an average of -6/-4 mm Hg and reduced heart rate by five beats per
      minute. Due to the larger sample size from the two unpublished studies,
      carvedilol provided a better estimate of BP lowering effect than labetalol. The
      BP lowering estimate from combining carvedilol once and twice the starting doses
      is -4/-3 mm Hg. Doses higher than the recommended starting dose did not provide
      additional BP reduction. Higher doses of dual receptor blockers caused more
      bradycardia than lower doses. Based on indirect comparison with other classes of
      drugs, the blood pressure lowering effect of dual alpha- and beta-receptor
      blockers is less than non-selective, beta1 selective and partial agonist beta
      blockers, as well as thiazides and drugs inhibiting the renin angiotensin system.
      Dual blockers also had little or no effect on reducing pulse pressure, which is
      similar to the other beta-blocker classes, but less than the average reduction of
      pulse pressure seen with thiazides and drugs inhibiting the renin angiotensin
      system. Patients taking dual receptor blockers were not more likely to withdraw
      from the study compared to patients taking placebo.

PMID- 26306579
TI  - Maternal hypothyroxinaemia in early pregnancy and school performance in 5-year
      old offspring.
AB  - OBJECTIVE: Overt hypothyroidism in pregnant women is associated with a lower
      intelligence quotient in their children. More recently, subtle decreases in
      maternal thyroid function have also been associated with neurodevelopmental
      impairment in offspring. We tested the effect of hypothyroxinaemia during early
      pregnancy on school performance. DESIGN: This was a longitudinal study that
      included the data of 1196 mother-child pairs from the Amsterdam Born Children and
      Their Development study. METHODS: Maternal serum free thyroxine (T4) and TSH were
      obtained at a median gestational age of 12.9 (interquartile range: 11.9-14.3)
      weeks. School performance was assessed at age 5 years and based on scores
      obtained in arithmetic and language tests from the national monitoring and
      evaluation system. Poor school performance was defined as a test result <25th
      percentile and subnormal school performance as a result <50th percentile of the
      norm population. To estimate the impact of possible non-response bias, we
      conducted inverse-probability weighted analyses. RESULTS: Maternal
      hypothyroxinaemia (i.e., a maternal free T4 in the lowest 10% of distribution)
      was associated with a 1.61 (95% CI: 1.05-2.47) -fold increased odds of subnormal
      arithmetic performance after adjustment for confounders (P=0.03). However, the
      odds ratio dropped to 1.48 (95% CI: 0.94-2.32) after inverse-probability
      weighting (P=0.09). No such relations were found with TSH. CONCLUSIONS: Maternal
      hypothyroxinaemia at the end of the first trimester was associated with reduced
      performance in an arithmetic test, but not in a language test, in 5-year-old
      offspring. However, our results should be interpreted carefully because of
      possible non-response bias.

PMID- 26306580
TI  - Cry of the brain.

PMID- 26306581
TI  - Transzygomatic approach with anteriorly limited inferior temporal gyrectomy for
      large medial tentorial meningiomas.
AB  - BACKGROUND: Tentorial meningiomas near the middle third of the medial tentorial
      edge with supratentorial extension are usually removed via the subtemporal
      approach. This approach, however, may not be practical, especially for huge
      tumors extending to the posterior subtemporal space. This study describes the use
      of the transzygomatic approach with anteriorly limited inferior temporal
      gyrectomy (TZ-AITG) to remove these large tumors. METHODS: Between 2008 and 2012,
      five patients with symptomatic tentorial meningiomas (median diameter, 5.2 cm;
      range, 4.0-5.7 cm) near the middle third of the medial tentorial edge with
      supratentorial extension underwent TZ-AITG, consisting of zygomatic osteotomy,
      low-positioned craniotomy, and resection of the inferior temporal gyrus around 4
      cm from the tip. RESULTS: Tumors were completely resected in all patients.
      Postoperatively, none had a newly developed neurological morbidity, and none
      died. Of three patients with preoperative hemianopia, two showed improvement and
      one remained stationary. One patient with preoperative hemiparesis recovered
      completely. All patients returned to their normal activities during the follow-up
      period. Surgical morbidities included epidural hematoma and chronic subdural
      hematoma in one patient each, with both requiring evacuation. CONCLUSIONS: TZ
      AITG may be a good alternative to the subtemporal approach for large tentorial
      meningiomas near the middle third of the medial tentorial edge. TZ-AITG provides
      access to the lesions and visualization of the middle fossa, facilitating early
      feeder control while minimizing brain retraction, thus reducing potential injury
      to the vein of Labbe. TZ-AITG is also safe and feasible in minimizing
      neurological compromise.

PMID- 26306582
TI  - Posttraumatic cerebral infarction in severe traumatic brain injury:
      characteristics, risk factors and potential mechanisms.
AB  - BACKGROUND: Posttraumatic cerebral infarction (PTCI) is a severe secondary insult
      of traumatic brain injury (TBI). This study aimed to evaluate the characteristics
      and risk factors of PTCI after severe TBI (sTBI) and explore possible mechanism.
      METHODS: This retrospective study included a cohort of 339 patients with sTBI;
      they were divided into the PTCI and non-PTCI groups. Clinical data and follow-up
      charts were reviewed for comparison. The logistic regression model was used for
      multivariate analysis to detect the risk factors of PTCI. The Glasgow Outcome
      Scale (GOS) and Barthel index (BI) for activities of daily living (ADL) were
      applied to evaluate their outcome. RESULTS: PTCI led to an increased mortality
      (43.5 % vs. 10.7 %, P < 0.001) and days of intensive care unit stay (14.3 days
      vs. 7.1 days, P < 0.001), decreased GOS (3.1 vs. 4.1, P < 0.001) and BI (25.0 vs.
      77.9, P < 0.001). Increased infarction volume led to poor outcome assessed by GOS
      (r = -0.46, P < 0.0001) and BI for ADL (r = -0.36, P = 0.026) for surviving
      patients. Compared with non-PTCI patients, PTCI patients had a high incidence of
      midline shift (36.2 % vs. 20.7 %, P = 0.011) and posttraumatic vasospasm (PTV)
      (42.0 % vs. 27.4 %, P = 0.027). Daily prevalence of PTCI occurred in two peaks:
      one (73.9 %) was in the first 24 h after injury, while the other (18.8 %) was in
      the span of 43 to 60 h postinjury. In multivariate analysis, hyperthermia
      [adjusted odds ratio (OR), 3.11; P = 0.001] in the first 24 h, thrombocytopenia
      (OR, 27.08; P < 0.001), abnormal prothrombin time (OR, 7.66; P < 0.001) and
      traumatic subarachnoid hemorrhage (OR, 2.33; P = 0.022) were independent
      predictors for PTCI. CONCLUSIONS: PTCI deteriorates the outcome of sTBI patients.
      Mechanical compression and hemocoagulative disturbance serve as potential
      mechanisms mediating this pathophysiological process. PTV may also contribute to
      PTCI, but its association with PTCI is weak and needs further exploration. Early
      recognition and intervention of these factors might be beneficial for preventing
      PTCI.

PMID- 26306583
TI  - Tuberculous ulcer of scalp--a forgotten entity.

PMID- 26306585
TI  - Polymer Solar Cells: Solubility Controls Fiber Network Formation.
AB  - The photoactive layer of polymer solar cells is commonly processed from a four
      component solution, containing a semiconducting polymer and a fullerene
      derivative dissolved in a solvent-cosolvent mixture. The nanoscale dimensions of
      the polymer-fullerene morphology that is formed upon drying determines the solar
      cell performance, but the fundamental processes that govern the size of the phase
      separated polymer and fullerene domains are poorly understood. Here, we
      investigate morphology formation of an alternating copolymer of
      diketopyrrolopyrrole and a thiophene-phenyl-thiophene oligomer (PDPPTPT) with
      relatively long 2-decyltetradecyl (DT) side chains blended with [6,6]-phenyl-C71
      butyric acid methyl ester. During solvent evaporation the polymer crystallizes
      into a fibrous network. The typical width of these fibers is analyzed by
      quantification of transmission electron microscopic images, and is mainly
      determined by the solubility of the polymer in the cosolvent and the molecular
      weight of the polymer. A higher molecular weight corresponds to a lower
      solubility and film processing results in a smaller fiber width. Surprisingly,
      the fiber width is not related to the drying rate or the amount of cosolvent. We
      have made solar cells with fiber widths ranging from 28 to 68 nm and found an
      inverse relation between fiber width and photocurrent. Finally, by mixing two
      cosolvents, we develop a ternary solvent system to tune the fiber width. We
      propose a model based on nucleation-and-growth which can explain these
      measurements. Our results show that the width of the semicrystalline polymer
      fibers is not the result of a frozen dynamical state, but determined by the
      nucleation induced by the polymer solubility. 

PMID- 26306584
TI  - Fractures in bone tumour prosthesis.
AB  - PURPOSE: The aim of the present narrative review is to report the different
      aspects related to the fractures around tumour prosthetic implants in terms of
      technical and medical issues. METHODS: A non systematic literature review on the
      topic was performed. RESULTS: Given the increased rate of limb salvage procedures
      and megaprostheses implanted for bone tumours, the increased number of
      osteoporotic periprosthetic fractures, and the burden of revision arthroplasty,
      the number of surgeries using endoprosthetic implants is likely to increase in
      the near future. Surgeons will face more frequently the complications related to
      tumour endoprosthetic implant. Endoprosthetic reconstruction has a higher risk of
      intra-operative and post-operative complications compared to conventional
      prosthetic replacement. CONCLUSIONS: Very rare reports and recommendations are
      available in literature regarding the treatment of periprosthetic fractures after
      megaprosthesis, and there is currently no consensus about which should be the
      standard management for periprosthetic fractures in this population of patients.

PMID- 26306586
TI  - Stenting as a bail-out option after failed percutaneous transluminal angioplasty
      in infrainguinal vein bypass grafts.
AB  - OBJECTIVES: To study the safety and efficacy of bare and covered stents in
      infrainguinal vein grafts after failure of PTA for treating graft stenoses.
      METHODS: An analysis of a prospective database of all patients who underwent
      stenting of infrainguinal vein bypass grafts at this institution between 1
      January 2008 and 31 December 2012 was carried out. The main outcome considered
      was primary patency, which was reported at 1, 6 and 12 months. RESULTS: A total
      of 18 patients with a mean age of 73 years (range: 56 to 86) were included. The
      indications for stent placement were significant recoil (7, 39%), graft rupture
      (6, 33%), residual vein cusps (3, 17%) and aneurysmal degeneration (2, 11%).
      There was a high overall technical success rate of 94% (17/18) and arrest of
      haemorrhage was achieved in all cases of graft rupture. The primary patency at 1,
      6 and 12 months was 89%, 71% and 59%, respectively. CONCLUSION: The use of bare
      and covered stents in infrainguinal vein grafts appears safe and effective. They
      are an excellent bail-out option for the treatment of graft rupture and give
      acceptable short-term results.

PMID- 26306587
TI  - Counteraction of Apoptotic and Inflammatory Effects of Adriamycin in the Liver
      Cell Culture by Clinopitolite.
AB  - Growing evidence has been reported on adriamycin (ADR) hepatotoxicity in
      literature. Hepatotoxicity caused by the use of drugs has a serious undesirable
      effect in the cure of cancer patients that needs to be eliminated. The exact
      mechanism of ADR on non-cancerous tissue still remains to be a mystery. The
      zeolite (clinoptilolite) minerals form a complex group of aluminosilicates that
      often occur as accessory minerals in intermediate and basic rocks. In light of
      this information, we investigated the possible anti-inflammatory and anti
      apoptotic effects of clinoptilolite in ADR that is inducing the toxicity in
      primary liver cell culture. Primary liver cell culture from rat was used in the
      study. We had three experiment groups including the following: (1) cells treated
      only with 50 MUM ADR for 24 h, (2) cells treated with the 50 MUM ADR for 24 h and
      then treated with 10(-4) M zeolite for 1 h, and (3) cells were incubated with 50
      MUM ADR for 24 h and then incubated with 10(-4) M zeolite for 24 h to test its
      long-term effects. After that, western blotting was performed in order to
      evaluate protein expression levels of several inflammation markers including IL
      1beta, tumor necrosis factor (TNF)-alpha, and nuclear factor kappa B (NF-kappaB),
      and immunohistochemistry was carried out to detect apoptosis in liver cell
      culture. Also, TdT-dUTP Terminal Nick-End Labeling (TUNEL) method was used for
      detecting apoptosis. We found elevated levels of inflammatory protein and
      apoptotic markers in ADR-administered cells (p < 0.05). Inflammatory and
      apoptotic markers decreased significantly after treated with zeolite (p < 0.05).
      The present study was pointed out that ADR causes hepatotoxicity via apoptosis
      and/or inflammation processes resulting from initiator NF-kappaB and TNF which
      causes proinflammatory mediators such as IL-1beta. Elevation of inflammation
      might give rise to trigger apoptosis. Clinoptilolite counteracted the apoptosis
      and inflammation induced by ADR arising from the decrease in NF-kappaB, TNF
      alpha, and IL-1beta protein levels.

PMID- 26306588
TI  - Essential Elements and Their Relations to Phenolic Compounds in Infusions of
      Medicinal Plants Acquired from Different European Regions.
AB  - The aim of this research was to compare chemical composition of herbs acquired
      from different European countries. The concentrations of P, Fe, Mn, Zn, Cu,
      phenolic compounds, and the antioxidant activity were determined in infusions of
      27 medicinal herbs (7 species) from Lithuania, Serbia, Italy, and Portugal. Total
      and extractable P were expressed in milligrams per liter and metals in micrograms
      per liter and followed the sequence: Fe > Mn > Zn > Cu, while antioxidant
      activity ranged from 29.4 to 217.8 mg of Trolox equivalent (TE) per liter. Total
      flavonoids were in the range of 20.5-95.1 mg L(-1). The rank order of phenolic
      compounds assayed by HPLC method (in mg L(-1) of infusion) was as follows: rutin
      > myricetin > quercetin > kaempferol, and chlorogenic > ferulic > p-coumaric >
      caffeic > gallic acids. Significant correlations were found between total P
      inorganic phosphate P, Zn-Mn, Mn-Cu, total flavonoids-antioxidant activity, and
      quercetin with caffeic and ferulic acids. Generally, medicinal plant infusions
      differed in their chemical composition, strongly depending on plant species,
      regardless of the origin from distant geographical areas of Europe. Principal
      component analysis selected the concentrations of Cu, Mn, total and inorganic
      phosphate P, as factors which strongly influence differentiation of the samples.
      Moreover, infusions from Hyperici herba and Helichrysi inflorescentia contained
      significant amounts of water-extractable Mn and Fe forms as claimed by the
      Dietary Reference Intakes for humans.

PMID- 26306589
TI  - Urinary Magnesium, Calcium, and Phosphorus to Creatinine Ratios of Healthy
      Elementary School Lebanese Children.
AB  - Urinary magnesium (Mg), calcium (Ca), and phosphorus (P) excretions are known to
      vary greatly between populations due to dietary habits, physical activity,
      mineral content of water, climate, genetics, and race. Thus, it is essential to
      determine the normal values in each population in order to assess the status as
      well as to diagnose any possible abnormality of metabolisms especially
      hypercalciuria. A study was conducted to determine urinary Mg/creatinine (Cr),
      Ca/Cr, and P/Cr ratios of healthy Lebanese elementary schoolchildren. Using a
      multi-stage cluster sampling at district, school, and class levels, a sample of
      1403 children (781 boys and 622 girls), from 26 different schools, was selected.
      Non-fasting morning urine samples and anthropometric data were collected and
      analyzed. The mean Mg/Cr, Ca/Cr, and P/Cr ratios were 0.122 +/- 0.075 mg/mg
      (0.568 +/- 0.348 mM/mM), 0.084 +/- 0.101 mg/mg (0.237 +/- 0.286 mM/mM), and 0.692
      +/- 0.417 mg/mg (2.527 +/- 1.524 mM/mM), respectively, with no significant
      difference between boys and girls (P = 0.706, 0.161, and 0.604; respectively).
      The 95th percentile of Mg/Cr, Ca/Cr, and P/Cr ratios fluctuated with age, showing
      a sharp decrease in Ca/Cr and P/Cr at the age of 10. The mean Mg/Cr, Ca/Cr, and
      P/Cr ratios were comparable to those of similar age groups in other populations.
      The 95th percentiles of Mg/Cr, Ca/Cr, and P/Cr ratios were 0.26 mg/mg (1.23
      mM/mM), 0.27 mg/mg (0.76 mM/mM), and 1.48 mg/mg (5.40 mM/mM), respectively. These
      values can be used as cutoffs to detect abnormalities in these three minerals'
      metabolisms among healthy Lebanese children.

PMID- 26306590
TI  - Mechanistic and Kinetic Study of Singlet O2 Oxidation of Methionine by On-Line
      Electrospray Ionization Mass Spectrometry.
AB  - We report a reaction apparatus developed to monitor singlet oxygen ((1)O2)
      reactions in solution using on-line ESI mass spectrometry and spectroscopy
      measurements. (1)O2 was generated in the gas phase by the reaction of H2O2 with
      Cl2, detected by its emission at 1270 nm, and bubbled into aqueous solution
      continuously. (1)O2 concentrations in solution were linearly related to the
      emission intensities of airborne (1)O2, and their absolute scales were
      established based on a calibration using 9,10-anthracene dipropionate dianion as
      an (1)O2 trapping agent. Products from (1)O2 oxidation were monitored by UV-Vis
      absorption and positive/negative ESI mass spectra, and product structures were
      elucidated using collision-induced dissociation-tandem mass spectrometry. To
      suppress electrical discharge in negative ESI of aqueous solution, methanol was
      added to electrospray via in-spray solution mixing using theta-glass ESI
      emitters. Capitalizing on this apparatus, the reaction of (1)O2 with methionine
      was investigated. We have identified methionine oxidation intermediates and
      products at different pH, and measured reaction rate constants. (1)O2 oxidation
      of methionine is mediated by persulfoxide in both acidic and basic solutions.
      Persulfoxide continues to react with another methionine, yielding methionine
      sulfoxide as end-product albeit with a much lower reaction rate in basic
      solution. Density functional theory was used to explore reaction potential energy
      surfaces and establish kinetic models, with solvation effects simulated using the
      polarized continuum model. Combined with our previous study of gas-phase
      methionine ions with (1)O2, evolution of methionine oxidation pathways at
      different ionization states and in different media is described.

PMID- 26306591
TI  - Mimicking Livor Mortis: a Well-Known but Unsubstantiated Color Profile in
      Sapromyiophily.
AB  - By emitting strong scents resembling rotting organic materials suitable for
      oviposition and/or foraging of flies, sapromyiophilous flowers mimic the
      substrates that attract flies as pollinators. It has been suggested that the wide
      range of volatile organic compounds emitted by this deceptive pollination system
      reflects the trophic preferences of flies to different types of substrate,
      including herbivore and carnivore feces, carrion, and fruiting bodies of fungi.
      Previous studies suggest that floral scents play a particularly important role in
      sapromyiophily. However, few studies on the relative importance of floral color
      or synergy between visual and olfactory cues in sapromyiophily have been
      substantiated. In this study, we analyzed fetid floral odor, floral pigment
      composition, and reflectance of an Amorphophallus konjac C. Koch inflorescence,
      and we conducted bioassays with different visual and/or olfactory cues to explore
      an unsubstantiated color profile in sapromyiophily: mimicking livor mortis. Our
      analysis showed A. konjac can emit oligosulphide-dominated volatile blends
      similar to those emitted by carrion. Necrophagous flies cannot discriminate
      between the color of an inflorescence, livor mortis, and floral pigments. We
      concluded that mimicking livor mortis may represent a common tactic of pollinator
      attraction in "carrion flower" systems within angiosperms. 

PMID- 26306592
TI  - Maize Plants Recognize Herbivore-Associated Cues from Caterpillar Frass.
AB  - Caterpillar behaviors such as feeding, crawling, and oviposition are known to
      induce defenses in maize and other plant species. We examined plant defense
      responses to another important caterpillar behavior, their defecation. Fall
      armyworms (FAW, Spodoptera frugiperda), a major threat to maize (Zea mays), are
      voracious eaters and deposit copious amounts of frass in the enclosed whorl
      tissue surrounding their feeding site, where it remains for long periods of time.
      FAW frass is composed of molecules derived from the host plant, the insect
      itself, and associated microbes, and hence provides abundant cues that may alter
      plant defense responses. We observed that proteins from FAW frass initially
      induced wound-responsive defense genes in maize; however, a pathogenesis-related
      (pr) defense gene was induced as the time after application increased.
      Elicitation of pathogen defenses by frass proteins was correlated with increased
      herbivore performance and reduced fungal pathogen performance over time. These
      responses differ from the typical plant response to oral secretions of the FAW.
      The results pave the way for identification of protein molecule(s) from the
      excretion of an herbivore that elicits pathogen defense responses while
      attenuating herbivore defenses in plants. 

PMID- 26306593
TI  - Intermittent inotrope therapy: evidence or belief?

PMID- 26306595
TI  - Superhydrophobic Surfaces Boost Fibril Self-Assembly of Amyloid beta Peptides.
AB  - Amyloid beta (Abeta) peptides are the main constituents of Alzheimer's amyloid
      plaques in the brain. Here we report how the unique microfluidic flows exerted by
      droplets sitting on superhydrophobic surfaces can influence the aggregation
      mechanisms of several Abeta fragments by boosting their fibril self-assembly.
      Abeta(25-35), Abeta(1-40), and Abeta(12-28) were dried both on flat hydrophilic
      surfaces (contact angle (CA) = 37.3 degrees ) and on nanostructured
      superhydrophobic ones (CA = 175.8 degrees ). By embedding nanoroughened surfaces
      on top of highly X-ray transparent Si3N4 membranes, it was possible to probe the
      solid residues by raster-scan synchrotron radiation X-ray microdiffraction
      (MUXRD). As compared to residues obtained on flat Si3N4 membranes, a general
      enhancement of fibrillar material was detected for all Abeta fragments dried on
      superhydrophobic surfaces, with a particular emphasis on the shorter ones.
      Indeed, both Abeta(25-35) and Abeta(12-28) showed a marked crystalline cross-beta
      phase with varying fiber textures. The homogeneous evaporation rate provided by
      these nanostructured supports, and the possibility to use transparent membranes,
      can open a wide range of in situ X-ray and spectroscopic characterizations of
      amyloidal peptides involved in neurodegenerative diseases and for the fabrication
      of amyloid-based nanodevices. 

PMID- 26306594
TI  - Blood pressure reductions following catheter-based renal denervation are not
      related to improvements in adherence to antihypertensive drugs measured by
      urine/plasma toxicological analysis.
AB  - Renal denervation can reduce blood pressure in patients with uncontrolled
      hypertension. The adherence to prescribed antihypertensive medication following
      renal denervation is unknown. This study investigated adherence to prescribed
      antihypertensive treatment by liquid chromatography-high resolution tandem mass
      spectrometry in plasma and urine at baseline and 6 months after renal denervation
      in 100 patients with resistant hypertension, defined as baseline office systolic
      blood pressure >=140 mmHg despite treatment with >=3 antihypertensive agents. At
      baseline, complete adherence to all prescribed antihypertensive agents was
      observed in 52 patients, 46 patients were partially adherent, and two patients
      were completely non-adherent. Baseline office blood pressure was 167/88 +/- 19/16
      mmHg with a corresponding 24-h blood pressure of 154/86 +/- 15/13 mmHg. Renal
      denervation significantly reduced office and ambulatory blood pressure at 6-month
      follow-up by 15/5 mmHg (p < 0.001/p < 0.001) and 8/4 mmHg (p < 0.001/p = 0.001),
      respectively. Mean adherence to prescribed treatment was significantly reduced
      from 85.0 % at baseline to 80.7 %, 6 months after renal denervation (p = 0.005).
      The blood pressure decrease was not explained by improvements in adherence
      following the procedure. Patients not responding to treatment significantly
      reduced their drug intake following the procedure. Adherence was highest for
      angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and beta
      blockers (>90 %) and lowest for vasodilators (21 %). In conclusion, renal
      denervation can reduce office and ambulatory blood pressure in patients with
      resistant hypertension despite a significant reduction in adherence to
      antihypertensive treatment after 6 months. 

PMID- 26306597
TI  - Skeletal muscle AMP-activated protein kinase gamma1(H151R) overexpression
      enhances whole body energy homeostasis and insulin sensitivity.
AB  - AMP-activated protein kinase (AMPK) is a major sensor of energy homeostasis and
      stimulates ATP-generating processes such as lipid oxidation and glycolysis in
      peripheral tissues. The heterotrimeric enzyme consists of a catalytic alpha
      subunit, a beta-subunit that is important for enzyme activity, and a noncatalytic
      gamma-subunit that binds AMP and activates the AMPK complex. We generated a
      skeletal muscle Cre-inducible transgenic mouse model expressing a mutant gamma1
      subunit (AMPKgamma1(H151R)), resulting in chronic AMPK activation. The expression
      of the predominant AMPKgamma3 isoform in skeletal muscle was reduced in extensor
      digitorum longus (EDL) muscle (81-83%) of AMPKgamma1(H151R) transgenic mice,
      whereas the abundance and phosphorylation of the AMPK target acetyl-CoA
      carboxylase was increased in tibialis anterior muscle. Glycogen content was
      increased 10-fold in gastrocnemius muscle. Whole body carbohydrate oxidation was
      increased by 11%, and whereas glucose tolerance was unaffected, insulin
      sensitivity was increased in AMPKgamma1(H151R) transgenic mice. Furthermore,
      perigonadal white adipose tissue mass and serum leptin were reduced in female
      AMPKgamma1(H151R) transgenic mice by 38 and 51% respectively. Conversely, in male
      AMPKgamma1(H151R) transgenic mice, food intake was increased (14%), but body
      weight and body composition were unaltered, presumably because of increased
      energy expenditure. In conclusion, transgenic activation of skeletal muscle
      AMPKgamma1 in this model plays an important sex-specific role in skeletal muscle
      metabolism and whole body energy homeostasis. 

PMID- 26306596
TI  - IL-1beta reciprocally regulates chemokine and insulin secretion in pancreatic
      beta-cells via NF-kappaB.
AB  - Proinflammatory cytokines impact islet beta-cell mass and function by altering
      the transcriptional activity within pancreatic beta-cells, producing increases in
      intracellular nitric oxide abundance and the synthesis and secretion of
      immunomodulatory proteins such as chemokines. Herein, we report that IL-1beta, a
      major mediator of inflammatory responses associated with diabetes development,
      coordinately and reciprocally regulates chemokine and insulin secretion. We
      discovered that NF-kappaB controls the increase in chemokine transcription and
      secretion as well as the decrease in both insulin secretion and proliferation in
      response to IL-1beta. Nitric oxide production, which is markedly elevated in
      pancreatic beta-cells exposed to IL-1beta, is a negative regulator of both
      glucose-stimulated insulin secretion and glucose-induced increases in
      intracellular calcium levels. By contrast, the IL-1beta-mediated production of
      the chemokines CCL2 and CCL20 was not influenced by either nitric oxide levels or
      glucose concentration. Instead, the synthesis and secretion of CCL2 and CCL20 in
      response to IL-1beta were dependent on NF-kappaB transcriptional activity. We
      conclude that IL-1beta-induced transcriptional reprogramming via NF-kappaB
      reciprocally regulates chemokine and insulin secretion while also negatively
      regulating beta-cell proliferation. These findings are consistent with NF-kappaB
      as a major regulatory node controlling inflammation-associated alterations in
      islet beta-cell function and mass. 

PMID- 26306598
TI  - CB1R antagonist increases hepatic insulin clearance in fat-fed dogs likely via
      upregulation of liver adiponectin receptors.
AB  - The improvement of hepatic insulin sensitivity by the cannabinoid receptor 1
      (CB1R) antagonist rimonabant (RIM) has been recently been reported to be due to
      upregulation of adiponectin. Several studies demonstrated that improvement in
      insulin clearance accompanies the enhancement of hepatic insulin sensitivity.
      However, the effects of RIM on hepatic insulin clearance (HIC) have not been
      fully explored. The aim of this study was to explore the molecular mechanism(s)
      by which RIM affects HIC, specifically to determine whether upregulation of liver
      adiponectin receptors (ADRs) and other key genes regulated by adiponectin mediate
      the effects. To induce insulin resistance in skeletal muscle and liver, dogs were
      fed a hypercaloric high-fat diet (HFD) for 6 wk. Thereafter, while still
      maintained on a HFD, animals received RIM (HFD+RIM; n = 11) or placebo (HFD+PL; n
      = 9) for an additional 16 wk. HIC, calculated as the metabolic clearance rate
      (MCR), was estimated from the euglycemic-hyperinsulinemic clamp. The HFD+PL group
      showed a decrease in MCR; in contrast, the HFD+RIM group increased MCR.
      Consistently, the expression of genes involved in HIC, CEACAM-1 and IDE, as well
      as gene expression of liver ADRs, were increased in the HFD+RIM group, but not in
      the HFD+PL group. We also found a positive correlation between CEACAM-1 and the
      insulin-degrading enzyme IDE with ADRs. Interestingly, expression of liver genes
      regulated by adiponectin and involved in lipid oxidation were increased in the
      HFD+RIM group. We conclude that in fat-fed dogs RIM enhances HIC, which appears
      to be linked to an upregulation of the adiponectin pathway. 

PMID- 26306599
TI  - Alterations of plasma metabolite profiles related to adipose tissue distribution
      and cardiometabolic risk.
AB  - Metabolomic profiling of obese individuals revealed altered concentrations of
      many metabolites, especially branched-chain amino acids (BCAA), possibly linked
      to altered adipose tissue BCAA catabolism. We tested the hypothesis that some
      features of this metabolite signature relate closely to visceral obesity and
      concomitant alterations in cardiometabolic risk factors. We also postulated that
      alterations in BCAA-catabolizing enzymes are predominant in visceral adipose
      tissue. Fifty-nine women (BMI 20-41 kg/m(2)) undergoing gynecologic surgery were
      recruited and characterized for overall and regional adiposity, blood metabolite
      levels using targeted metabolomics, and cardiometabolic risk factors. Adipose
      samples (visceral and subcutaneous) were obtained and used for gene expression
      and Western blot analyses. Obese women had significantly higher circulating BCAA
      and kynurenine/tryptophan (Kyn/Trp) ratio than lean or overweight women (P <
      0.01). Principal component analysis confirmed that factors related to AA and the
      Kyn/Trp ratio were positively associated with BMI, fat mass, visceral or
      subcutaneous adipose tissue area, and subcutaneous adipocyte size (P <= 0.05). AA
      related factor was positively associated with HOMA-IR (P <= 0.01). Factors
      reflecting glycerophospholipids and sphingolipids levels were mostly associated
      with altered blood lipid concentrations (P <= 0.05). Glutamate level was the
      strongest independent predictor of visceral adipose tissue area (r = 0.46, P <
      0.001). Obese women had lower expression and protein levels of BCAA-catabolizing
      enzymes in visceral adipose tissue than overweight or lean women (P <= 0.05). We
      conclude that among metabolites altered in obesity plasma concentrations of BCAA
      and the Kyn/Trp ratio are closely related to increased adiposity. Alterations in
      expression and protein levels of BCAA-catabolizing enzymes are predominant in
      visceral adipose tissue. 

PMID- 26306601
TI  - Restrictive blood transfusion strategies and associated infection in orthopedic
      patients: a meta-analysis of 8 randomized controlled trials.
AB  - This study sought to evaluate whether restrictive blood transfusion strategies
      are associated with a risk of infection in orthopedic patients by conducting a
      meta-analysis of randomized controlled trials (RCTs). RCTs with restrictive
      versus liberal red blood cell (RBC) transfusion strategies were identified by
      searching Medline, Embase, the Cochrane Central Register of Controlled Trials and
      the Cochrane Database of Systematic Reviews from their inception to December
      2014. Eight RCTs with infections as outcomes were included in the final analysis.
      According to the Jadad scale, all studies were considered to be of high quality.
      The pooled risk ratio [RR] for the association between transfusion strategy and
      infection was 0.65 (95% CI, 0.47-0.91; p = 0.012), and the number of patients
      needed to treat to avoid an infection using a restrictive transfusion strategy
      was 62. No heterogeneity was observed. The sensitivity analysis indicated
      unstable results, and no significant publication bias was observed. This meta
      analysis of RCTs demonstrates that restrictive transfusion strategies in
      orthopedic patients result in a significant reduction in infections compared with
      more liberal strategies. 

PMID- 26306602
TI  - The Association Between Preoperative Symptoms of Obesity in Knee and Hip Joints
      and the Change in Quality of Life After Laparoscopic Roux-en-Y Gastric Bypass.
AB  - BACKGROUND: Weight loss after bariatric surgery is shown to reduce knee and hip
      pain in the majority of the severely obese. Studies indicate that with a
      reduction in musculoskeletal symptoms, quality of life (QoL) will improve. The
      group of severely obese with knee and hip symptoms might therefore have potential
      for a large improvement in QoL after a bariatric surgery. This study aimed
      therefore to assess the association between the degree of knee and hip symptoms
      before a laparoscopic Roux-en-Y gastric bypass (LRYGB) and the improvement of
      QoL, 1 year after the surgery, in severely obese. METHODS: This study is a
      historical cohort study based on data collected consecutively at the private
      hospital Molholm, Denmark. Before LRYGB surgery, 4548 severely obese completed a
      questionnaire on knee and hip symptoms of obesity and QoL. One year after
      surgery, 2862 (62.9 %) of the participants answered the same questionnaire again.
      RESULTS: Participants with moderate or severe knee or hip symptoms, before the
      surgery, experienced a statistically significantly larger improvement of their
      QoL, compared to participants without symptoms before the surgery. Furthermore,
      an association between the reduction of knee and hip symptoms and the improvement
      in QoL was found. CONCLUSIONS: Severely obese with moderate or severe
      preoperative knee and hip symptoms experienced a larger improvement of their QoL
      after a LRYGB compared to participants without symptoms before the operation.

PMID- 26306603
TI  - Preoperative Nutrition and Postoperative Discomfort in an ERAS Setting: A
      Randomized Study in Gastric Bypass Surgery.
AB  - BACKGROUND: Many patients experience postoperative nausea and vomiting (PONV).
      Preoperative treatment with carbohydrate solutions seems to improve the course
      after different types of surgery. This study was undertaken to investigate the
      potential value of different models for preoperative hydration/nutrition, in
      addition to our ERAS (enhanced recovery after surgery) protocol. METHODS: Ninety
      non-diabetic women planned for elective laparoscopic gastric bypass and aged 18
      65 years were included. All were on preoperative low-calorie diet (LCD). They
      were randomized into three arms, either a carbohydrate-rich drink, a protein
      enriched drink, or tap water and instructed to drink 800 and 200 mL 16 and 2 h,
      respectively, prior to operation. Risk factors for PONV were recorded
      preoperatively. All patients were operated before lunch and received 1500-2000 mL
      of Ringer-Acetate solution during the 24-30-h postoperative hospital time. Four
      variables (nausea, pain, tiredness, and headache) were registered on 100-mm
      visual analog scales six times over 22 h. The need for additional medication was
      registered. RESULTS: Out of 90 patients, 73 complete datasets were obtained.
      Nausea peaked at 7 p.m. but with no statistically significant differences between
      groups for any of the variables. Pain peaked the first 2 h postoperatively,
      remained longer, and had not returned to baseline values at 6 a.m. the morning
      after surgery but with no difference between groups. CONCLUSIONS: Inside our ERAS
      protocol, additional preoperative carbohydrate- or protein-enriched fluid
      treatment did not further reduce immediate patient discomfort in laparoscopic
      gastric bypass surgery.

PMID- 26306600
TI  - Puzzling role of genetic risk factors in human longevity: "risk alleles" as pro
      longevity variants.
AB  - Complex diseases are major contributors to human mortality in old age.
      Paradoxically, many genetic variants that have been associated with increased
      risks of such diseases are found in genomes of long-lived people, and do not seem
      to compromise longevity. Here we argue that trade-off-like and conditional
      effects of genes can play central role in this phenomenon and in determining
      longevity. Such effects may occur as result of: (i) antagonistic influence of
      gene on the development of different health disorders; (ii) change in the effect
      of gene on vulnerability to death with age (especially, from "bad" to "good");
      (iii) gene-gene interaction; and (iv) gene-environment interaction, among other
      factors. A review of current knowledge provides many examples of genetic factors
      that may increase the risk of one disease but reduce chances of developing
      another serious health condition, or improve survival from it. Factors that may
      increase risk of a major disease but attenuate manifestation of physical
      senescence are also discussed. Overall, available evidence suggests that the
      influence of a genetic variant on longevity may be negative, neutral or positive,
      depending on a delicate balance of the detrimental and beneficial effects of such
      variant on multiple health and aging related traits. This balance may change with
      age, internal and external environments, and depend on genetic surrounding. We
      conclude that trade-off-like and conditional genetic effects are very common and
      may result in situations when a disease "risk allele" can also be a pro-longevity
      variant, depending on context. We emphasize importance of considering such
      effects in both aging research and disease prevention. 

PMID- 26306605
TI  - Are trichomes involved in the biomechanical systems of Cucurbita leaf petioles?
AB  - MAIN CONCLUSION: Trichomes are involved in petiole movement and likely function
      as a part of the plant biomechanical system serving as an additional reservoir of
      hydrostatic pressure. The large, non-glandular trichomes on Cucurbita petioles
      occur across collenchyma strands. Time-lapse imaging was used to study the leaf
      reorientation of Cucurbita maxima 'Bambino' plants placed in horizontal position.
      The experiment comprised four variants of the large non-glandular petiole
      trichomes: (1) intact, (2) mechanically removed, (3) dehydrated, and (4) intact
      but with longitudinally injured petioles. Isolated strands of collenchyma with
      intact epidermis or epidermis mechanically removed from the abaxial and adaxial
      sides of the petiole were subjected to breaking test. The stiffness of the non
      isolated tissue with intact epidermis was measured using the micro-indentation
      method. Petioles without trichomes did not exhibit tropic response, and the
      dehydration of trichomes slowed and prevented complete leaf reorientation.
      Isolated strands of collenchyma showed no correlation between strength values and
      position on the petiole. However, strands of collenchyma with epidermis exhibited
      a significantly greater strength regardless of their position on the petiole. The
      indentation test showed that non-isolated collenchyma is stiffer on the abaxial
      side of the petiole. Trichomes from the abaxial side of the petiole were larger
      at their base. The application of the 'tensile triangles method' revealed that
      these trichomes had a biomechanically optimized shape in comparison to the
      adaxial side. We conclude that trichomes can be involved in plant biomechanical
      system and serve as an additional reservoir of hydrostatic pressure that is
      necessary for maintaining petioles in the prestressed state.

PMID- 26306604
TI  - Plant abiotic stress-related RCI2/PMP3s: multigenes for multiple roles.
AB  - MAIN CONCLUSION: RCI2 / PMP3 s participate in abiotic stress responses and impact
      the expression of other genes. Their multifunctionality is determined by
      differential expression and by distinct activities of their structurally
      different proteins. In plants, RCI2/PMP3 genes, which encode small membrane
      proteins of the PMP3 family, are closely associated with abiotic stress
      responses. Their involvement in mediating stress tolerance is supported by
      genetic evidence and overexpression studies. RCI2/PMP3s occur as multigenes in
      plant genomes and their encoded proteins belong to distinct and conserved
      structural groups. In addition, different isoforms appear to be targeted to the
      plasma membrane or to distinct endomembrane compartments in cells. Several
      studies have revealed that RCI2/PMP3 proteins participate in cell ion
      homeostasis, and in regulation of membrane stability and polarization. They also
      appear to potentiate plant transcriptional responses to abiotic stresses.
      However, their mechanisms of action remain unknown. This paper reviews the
      current knowledge of the multiple roles of plant RCI2/PMP3 genes resulting from
      their differential expression under normal and stress conditions. The structural
      diversity of RCI2/PMP3 proteins is analyzed and evidence supporting their
      functional specialization and possible activity mechanisms is examined. Finally,
      strategies are discussed for exploiting new and established technologies to
      overcome the difficulties posed by the multigene status of RCI2s and the integral
      membrane character of their proteins, enabling the probing of their individual
      functions and collective significance.

PMID- 26306607
TI  - Gravitational-Like Lens Based on Graphene Ripple.
AB  - We conducted a semiclassical study on carrier movement in curved graphene. A
      previous attempt was made to show that curved graphene is a readily available and
      cheap laboratory material used to study general relativity effects, especially if
      the electron energies satisfy 4MUeV ? |E| ? 3eV. Furthermore, a gravitational
      like lens can be constructed based on a special graphene ripple; this lens has
      neither chromatic nor cometic aberration. One can design an ideal electron lens
      using a graphene ripple.

PMID- 26306606
TI  - [Arthroscopic procedure for Baker's cysts : surgical technique. Video article].
AB  - BACKGROUND: Baker's cysts are related to increased intra-articular pressure. The
      causes may be inflammatory, degenerative or traumatic disorders. Owing to the
      increased intra-articular pressure a cyst protrudes between the semimembranosus
      and the medial gastrocnemius tendons. The traditional treatment for a Baker's
      cyst is open resection. As an alternative, an arthroscopic procedure can be
      performed, which is demonstrated by the video on surgical technique that
      accompanies this short report. SURGICAL TECHNIQUE: From the anterolateral portal
      the arthroscope is advanced through the intercondylar notch (below the posterior
      cruciate ligament) to the posteromedial recess. Under visual control, a
      posteromedial portal is created followed by identification of the capsular fold
      separating the cyst from the joint cavity. This fold (valvular mechanism) is
      resected with a shaver from the posteromedial portal until a large enough
      connection exists between the joint and the cyst (cyst decompression). After the
      decompression, the arthroscope is inserted from the posteromedial portal directly
      into the cyst cavity. Subsequently, the inner wall of the cyst is removed with
      the shaver via an additional far posterior cystic portal. It is obligatory to
      treat the associated intra-articular pathological condition. In our video a
      medial meniscal lesion is treated with partial meniscectomy.

PMID- 26306608
TI  - Access to primary care and the route of emergency admission to hospital:
      retrospective analysis of national hospital administrative data.
AB  - BACKGROUND: The UK government is pursuing policies to improve primary care
      access, as many patients visit accident and emergency (A and E) departments after
      being unable to get suitable general practice appointments. Direct admission to
      hospital via a general practitioner (GP) averts A and E use, and may reduce total
      hospital costs. It could also enhance the continuity of information between GPs
      and hospital doctors, possibly improving healthcare outcomes. OBJECTIVE: To
      determine whether primary care access is associated with the route of emergency
      admission-via a GP versus via an A and E department. METHODS: Retrospective
      analysis of national administrative data from English hospitals for 2011-2012.
      Adults admitted in an emergency (unscheduled) for >=1 night via a GP or an A and
      E department formed the study population. The measure of primary care access-the
      percentage of patients able to get a general practice appointment on their last
      attempt-was derived from a large, nationally representative patient survey.
      Multilevel logistic regression was used to estimate associations, adjusting for
      patient and admission characteristics. RESULTS: The analysis included 2 322 112
      emergency admissions (81.9% via an A and E department). With a 5 unit increase in
      the percentage of patients able to get a general practice appointment on their
      last attempt, the adjusted odds of GP admission (vs A and E admission) was
      estimated to increase by 15% (OR 1.15, 95% CI 1.12 to 1.17). The probability of
      GP admission if >=95% of appointment attempts were successful in each general
      practice was estimated to be 19.6%. This probability reduced to 13.6% when <80%
      of appointment attempts were successful. This equates to 139 673 fewer GP
      admissions (456 232 vs 316 559) assuming no change in the total number of
      admissions. Associations were consistent in direction across geographical regions
      of England. CONCLUSIONS: Among hospital inpatients admitted as an emergency,
      patients registered to more accessible general practices were more likely to have
      been admitted via a GP (vs an A and E department). This furthers evidence
      suggesting that access to general practice is related to use of emergency
      hospital services in England. The relative merits of the two admission routes
      remain unclear.

PMID- 26306609
TI  - How to build up the actionable knowledge base: the role of 'best fit' framework
      synthesis for studies of improvement in healthcare.
AB  - Increasing recognition of the role and value of theory in improvement work in
      healthcare offers the prospect of capitalising upon, and consolidating,
      actionable lessons from synthesis of improvement projects and initiatives. We
      propose that informed use of theory can (i) provide a mechanism by which to
      collect and organise data from a body of improvement work, (ii) offer a framework
      for analysis and identification of lessons learnt and (iii) facilitate an
      evaluation of the feasibility, effectiveness and acceptability of improvement
      programmes. Improvement practitioners can benefit from using an underpinning
      external structure as a lens by which to examine the specific achievements of
      their own projects alongside comparable initiatives led by others. We demonstrate
      the utility of a method known as 'best fit framework synthesis' (BFFS) in
      offering a ubiquitous and versatile means by which to collect, analyse and
      evaluate improvement work in healthcare. First reported in 2011, BFFS represents
      a pragmatic, flexible approach to integrating theory with findings from practice.
      A deductive phase, where a review team seeks to accommodate a substantial part of
      the data, is followed by an inductive phase, in which the team explores data not
      accommodated by the framework. We explore the potential for BFFS within
      improvement work by drawing upon the evidence synthesis methodology literature
      and practical examples of improvement work reported in BMJ Quality and Safety
      (2011-2015). We suggest four variants of BFFS that may have particular value in
      synthesising a body of improvement work. We conclude that BFFS, alongside other
      approaches that seek to optimise the contribution of theory to improvement work,
      represents one important enabling mechanism by which to establish the rigour and
      scientific credentials of the emerging discipline of 'improvement science'. 

PMID- 26306610
TI  - Prevention Services for Externalizing and Anxiety Symptoms in Low-Income
      Children: the Role of Parent Preferences in Early Childhood.
AB  - Dissemination of prevention programs targeting young children is impeded by
      challenges with parent engagement. Matching program characteristics to parent
      preferences is associated with increased retention in clinical/intervention
      settings, but little is known about the types of prevention programs that
      interest parents. The objectives of this study were to better understand parents'
      preferences for services designed to prevent externalizing and anxiety disorders
      and to identify factors associated with preferences. Ethnically diverse, low
      income caregivers (n = 485) of young children (11-60 months) completed surveys on
      child anxiety and externalizing symptoms, parental worry about their children,
      parent anxiety symptoms, and preferences for prevention group topics. Parents
      were more likely to prefer a group targeting externalizing behaviors compared to
      anxiety. Cluster analysis revealed four groups of children: low symptoms,
      moderate anxiety-low externalizing, moderate externalizing-low anxiety, and high
      anxiety and externalizing. Parents' preferences varied according to co-occurrence
      of child anxiety and externalizing symptoms; interest in a program targeting
      externalizing problems was associated with elevated externalizing problems
      (regardless of anxiety symptom level), parent anxiety symptoms, and parent worry
      about their child. Only parent anxiety symptoms predicted parents' interest in an
      anxiety-focused program, and preference for an anxiety-focused program was
      actually reduced if children had co-occurring anxiety and externalizing symptoms
      versus only anxiety symptoms. Results suggest that parents' interest in a program
      to prevent externalizing problems was well-aligned with the presenting problem,
      whereas preferences for anxiety programming suggest a more complex interplay
      among factors. Parent preferences for targeted programming are discussed within a
      broader framework of parent engagement.

PMID- 26306611
TI  - Molecular characterization of the genes involved in the secretion and immunity of
      lactococcin Q, a two-peptide bacteriocin produced by Lactococcus lactis QU 4.
AB  - Lactococcin Q is a two-peptide (Qalpha and Qbeta) bacteriocin produced by
      Lactococcus lactis QU 4, which exhibits specific antimicrobial activity against
      L. lactis strains. The lactococcin Q gene cluster (approximately 4.5 kb) was
      sequenced and found to include genes encoding lactococcin Q immunity (laqC), an
      ATP-binding cassette transporter (laqD) and a transport accessory protein (laqE),
      downstream of the lactococcin Q structural genes (laqA and laqB). In addition,
      the gene cluster showed high sequence identity with that of a lactococcin Q
      homologue bacteriocin, lactococcin G. Heterologous expression studies showed that
      LaqD was responsible for lactococcin Q secretion in a manner dependent on LaqE
      expression, and that LaqC conferred self-immunity to lactococcin Q and cross
      immunity to lactococcin G. Amino acid alignment of both lactococcin transporters
      revealed that LaqD contains an insertion (160-168 residues) that is essential for
      lactococcin Q secretion, as L. lactis cells that expressed LaqDDelta160-168 were
      devoid of this function. Additional experiments demonstrated that the
      LaqDDelta160-168 mutant was, however, able to secrete lactococcin G, suggesting
      that the insertion is necessary only for the lactococcin Q secretion by LaqD.
      This report demonstrates the biosynthetic mechanism of lactococcin Q/G-type
      bacteriocins and the complementarity of the genes responsible for the secretion
      of lactococcins Q and G. 

PMID- 26306612
TI  - An unusual case of a painful big toe.

PMID- 26306613
TI  - Free-Space Nanometer Wiring via Nanotip Manipulation.
AB  - Relentless efforts in semiconductor technology have driven nanometer-scale
      miniaturization of transistors, diodes, and interconnections in electronic chips.
      Free-space writing enables interconnections of stacked modules separated by an
      arbitrary distance, leading to ultimate integration of electronics. We have
      developed a free-space method for nanometer-scale wiring on the basis of
      manipulating a metallic nanotip while applying a bias voltage without radiative
      heating, lithography, etching, or electrodeposition. The method is capable of
      fabricating wires with widths as low as 1-6 nm and lengths exceeding 200 nm with
      a breakdown current density of 8 TA/m(2). Structural evolution and conduction
      during wire formation were analyzed by direct atomistic visualization using in
      situ high-resolution transmission electron microscopy. 

PMID- 26306614
TI  - Alfaxalone-butorphanol versus alfaxalone-morphine combination for immersion
      anaesthesia in oriental fire-bellied toads (Bombina orientalis).
AB  - Oriental fire-bellied toads (Bombina orientalis) are small semi-aquatic anuran
      species popular as both pets and laboratory animals. Although they are commonly
      anaesthetized to undergo clinical and experimental procedures, very little is
      known about their anaesthetic management. The aims of this prospective,
      randomized, cross-over experimental trial were to establish effective butorphanol
      and morphine concentrations to be added to alfaxalone for immersion anaesthesia
      (pilot study), and to compare the anaesthetic and antinociceptive effects of the
      two drug mixtures (alfaxalone-butorphanol and alfaxalone-morphine), in Bombina
      orientalis toads. For the actual trial, the toads were randomly assigned to one
      of two treatment groups: AB and AM, with seven animals in each group, which
      received alfaxalone-butorphanol and alfaxalone-morphine combinations,
      respectively, at the concentrations established during the pilot study. Heart
      rate, respiratory rate, von Frey filament threshold and response to nociceptive
      withdrawal (NWR), righting and myotactic reflexes were measured at 5 min
      intervals until return of righting reflex was observed. The investigator who
      carried out all the measurements was blinded to the treatment. Any undesired
      effect or complication was noted and recorded. The two treatments were found to
      be comparable in terms of onset and duration of anaesthesia, and occurrence of
      undesired effects. However, group AM resulted in lower NWR scores and higher von
      Frey filament thresholds than group AB. It is concluded that, at the investigated
      concentrations and in combination with alfaxalone by immersion, morphine provides
      better antinociception than butorphanol in oriental fire-bellied toads. 

PMID- 26306615
TI  - Porcine survival model to simulate acute upper gastrointestinal bleedings.
AB  - The existing animal models used for the simulation of acute gastrointestinal
      bleedings are usually non-survival models. We developed and evaluated a new
      porcine model (domestic pig, German Landrace) in which the animal remains alive
      and survives the artificial bleeding without any cardiovascular impairment. This
      consists of a bleeding catheter which is implanted into the stomach, then
      subcutaneously tunnelled from the abdomen to the neck where it is exteriorized
      and fixed with sutures. Using the injection of porcine blood, controllable and
      reproducible acute upper gastrointestinal bleeding can be simulated while
      maintaining normal gastrointestinal motility and physiology. Depending on the
      volume of blood applied through the gastric catheter, the bleeding intensity can
      be varied from traces of blood to a massive haemorrhage. This porcine model could
      be valuable, e.g. for testing the efficacy of new bleeding diagnostics in large
      animals before human use. 

PMID- 26306616
TI  - Future needs in peripheral neuropathy outcome measures.

PMID- 26306617
TI  - "He's probably more Mr. sport than me"--a qualitative exploration of mothers'
      perceptions of fathers' role in their children's physical activity.
AB  - BACKGROUND: Many children do not meet the recommended levels of physical
      activity. Parents can influence their children's physical activity in a number of
      ways but little research has focused on the impact of fathers. The current study
      aimed to explore how mothers perceived fathers to influence children's physical
      activity. METHODS: Telephone interviews with mothers (n = 50) who took part in a
      large cross sectional physical activity study were conducted. A strategic
      sampling method was applied to ensure varying deprivation levels and child
      physical activity. Interviews were based on children's physical activity and
      screen viewing behaviours and patterns. A total of 37 interviews included
      information on fathers and were used for the current study. Deductive content
      analysis was used to analyse the interviews. RESULTS: Mothers suggested that
      fathers are directly involved in their child's physical activity though co
      participation, whilst additionally playing an important role in encouraging and
      facilitating physical activity. The results suggest some variation in how mothers
      and fathers are involved in children's physical activity behaviours. Father
      availability seems to play a key role in the amount of physical activity
      involvement. CONCLUSIONS: Fathers play a key role in children's physical activity
      choices and behaviours and can influence children in a variety of ways. Parents
      tend to share in the physical activity related tasks of their children but father
      availability seems to be a factor in their amount of involvement. Health
      professionals aiming to improve child physical activity may benefit from
      developing interventions that target both children and fathers.

PMID- 26306618
TI  - Ambulatory medical services utilization for menstrual disorders among female
      personnel of different medical professions in Taiwan: a nationwide retrospective
      cohort study.
AB  - BACKGROUND: Menstrual disorders and their adverse symptoms can have a deleterious
      effect on both the private and working lives of women. Previous studies indicated
      that female nurses have elevated risk of menstrual disorders. Moreover, female
      nurses showed a higher incidence of ambulatory care visit for genitourinary
      diseases compared with other female medical personnel. However, little is known
      whether the medical services utilization for menstrual disorders were different
      among personnel from various medical professions. Therefore, the present study
      compared the ambulatory medical services utilization for menstrual disorders
      among personnel of six different medical professions in Taiwan using a
      nationwide, population-based health claim research database. METHODS: The
      National Health Insurance Research Database (NHIRD) was used to identify female
      medical professionals, aged 18 to 45 years, who obtained their licenses during
      January 1, 2000 to December 31, 2012. Personnel from six different medical
      professions were examined and they included (1) medical technologists and
      therapists, (2) registered nurses, (3) physicians, (4) doctors of Chinese
      medicine, (5) dentists, and (6) pharmacists. Diagnoses of menstrual disorders,
      based on International Classification of Diseases, Ninth Revision, Clinical
      Modification (ICD-9-CM) codes, were obtained from the ambulatory medical services
      utilization that occurred after their license date. Cox proportional hazards
      model was used to assess the hazards of medical services utilization for
      menstrual disorders using medical technologists and therapists as the reference
      category. RESULTS: A total of 7653 medical personnel were included in the
      analysis. Using the group containing medical technologists and therapists as the
      reference category, registered nurses (adjusted hazards ratio [AHR] = 1.13, p =
      0.018) and doctors of Chinese medicine (AHR = 2.52, p < 0.001) showed a
      significant increased risk of medical services utilization for menstrual
      disorders. Conversely, physicians showed a significant decreased risk of medical
      services utilization for menstrual disorders (AHR = 0.58, p < 0.001). Regarding
      the nine specific menstrual disorders observed in this study, registered nurses
      and doctors of Chinese medicine showed an increased risk in six and four of them,
      respectively. Pharmacists showed an increased risk only in menorrhagia (AHR =
      1.64, p = 0.020) and dentists showed no significant differences in any of the
      nine specific menstrual disorders compared with medical technologists and
      therapists. Physicians showed a significant decreased risk all specific menstrual
      disorders except menorrhagia and dysfunctional uterine bleeding. CONCLUSIONS:
      Findings from this population-based cohort study revealed that, compared with
      medical technologists and therapists, registered nurses and doctors of Chinese
      medicine exhibited significant increased risks in medical services utilization
      for menstrual disorders whereas physicians showed a significant decreased risk in
      menstrual disorders. Further studies should be conducted to delineate whether the
      differences in the medical services utilization is an indicator of risk of
      menstrual disorders or the results of varying patterns of health care seeking
      behavior among women of different medical professions.

PMID- 26306619
TI  - Expanding the role of the splicing USB1 gene from Poikiloderma with Neutropenia
      to acquired myeloid neoplasms.
AB  - Germline mutations of the U6 biogenesis 1 (USB1) gene underlie Poikiloderma with
      Neutropenia (PN), a rare autosomal recessive genodermatosis conferring an
      increased risk of myelodysplasia. Recent evidence highlights a key role of USB1
      protein in the splicing process, but nothing is known about USB1 alterations in
      acquired myelodysplastic syndromes, even though mutations in the spliceosome
      machinery represent an ubiquitous pathway in leukaemogenesis. By molecular
      cytogenetics and direct sequencing, we searched for USB1 deletions/duplications
      and point mutations in 141 bone marrow DNA samples from patients with
      myelodysplastic syndromes (n = 126), myelodysplastic/myeloproliferative neoplasms
      (n = 12) and acute myeloid leukaemia (n = 3). Three unreported variants, two in
      USB1 5'UTR (c.-83G>T and c.-66A>G), one in IVS3 (c.450-68dupT) and one (<1%) in
      IVS4 (c.587+21A>G/rs200924980) were detected. The germline nature could be proved
      for the c.-66A>G, but remains undefined for c.-83G>T and c.450-68dupT. Matched
      controls analysis did not reveal either 5' UTR variants in 290 chromosomes and
      Real-time polymerase chain reaction showed a slight reduction in bone marrow RNA
      levels of the patient with c.-66A>G. No USB1 rearrangements were detected by
      interphase fluorescence in situ hybridization. This pilot investigation on USB1
      expanded the variations repertoire of this gene, identifying three novel sequence
      variants, the role of which need further investigations in myeloid malignancies. 

PMID- 26306620
TI  - Screening for Pain in the Ambulatory Cancer Setting: Is 0-10 Enough?
AB  - PURPOSE: The purpose of this study was to explore concordance between patient
      self-reports of pain on validated questionnaires and discussions of pain in the
      ambulatory oncology setting. METHODS: Adult, ambulatory patients (N = 452) with
      all stages of cancer were included. Three pain measures were evaluated: two items
      from the Symptom Distress Scale (frequency [SDSF] and intensity [SDSI]) and the
      Pain Intensity Numeric Scale (PINS). Relevant pain was defined as: (1) scores 3
      of 5 on SDSF or SDSI or 5 of 10 on the (PINS); or (2) discussion of existing pain
      in an audio-recorded clinic visit. For each scale, McNemar's test assessed
      concordance of patient self-reports of relevant pain with discussions of relevant
      pain in the audio-recorded clinic visit. Sensitivity, specificity, and accuracy
      were calculated and a receiver operating characteristic analysis evaluated
      thresholds on self-report pain questionnaires to best identify relevant pain
      discussed in clinic. RESULTS: Identification of relevant pain by self-report was
      discordant (P < .001) with discussed pain coded in audio-recorded visits for all
      three measures. Specificity was higher for intensity (SDSI, 0.94; PINS, 0.97)
      than frequency (SDSF, 0.87); sensitivity was higher for frequency (SDSF, 0.35)
      than intensity (SDSI, 0.24; PINS, 0.12). Accuracy was higher for the SDS pain
      items (SDSF, 0.57; SDSI, 0.54) than for PINS (0.48). Receiver operating
      characteristic analysis curves suggest that lower threshold scores may improve
      the identification of relevant pain. CONCLUSION: Self-report pain screening
      measures favored specificity over sensitivity. Asking about pain frequency (in
      addition to intensity) and reconsidering threshold scores on pain intensity
      scales may be practical strategies to more accurately identify patients with
      cancer who have relevant pain.

PMID- 26306621
TI  - ReCAP: Feasibility and Accuracy of Extracting Cancer Stage Information From
      Narrative Electronic Health Record Data.
AB  - PURPOSE: Cancer stage, one of the most important prognostic factors for cancer
      specific survival, is often documented in narrative form in electronic health
      records (EHRs). Such documentation results in tedious and time-consuming
      abstraction efforts by tumor registrars and other secondary users. This
      information may be amenable to extraction by automated methods. METHODS: We
      developed a natural language processing algorithm to extract stage statements
      from machine-readable EHR documents, including automated rules to choose the most
      likely stage when discordance was present in the EHR. These methods were
      developed in a training set of patients with lung cancer, independently validated
      in a test set of patients with lung cancer, and compared with the gold standard
      of Vanderbilt Cancer Registry-determined stage (when available). RESULTS: In the
      combined data set of 2,323 patients (training set, n = 1,103; validation set, n =
      1,220), 751,880 documents were analyzed. A stage statement was extracted from
      2,239 (98.6%) patient EHRs (median, 24 documents per patient). Stage discordance
      was common, affecting 83.6% of these EHRs. Nevertheless, algorithmically derived
      stage accuracy was high in the validation set (kappa = 0.906; 95% CI, 0.873 to
      0.939), when including notes generated within 14 weeks from diagnosis.
      CONCLUSION: Accurate stage determination can be achieved through automated
      methods applied to narrative text, despite the frequent presence of discordance
      in such data. Our results also indicate that stage can be automatically captured
      in a shorter timeframe than the 6-month window used by cancer registries, as
      early as 5 weeks from diagnosis. These methods may be generalizable to large
      narrative cancer data sets.

PMID- 26306622
TI  - Simple viral/minimal piggyBac hybrid vectors for stable production of self
      inactivating gamma-retroviruses.
AB  - BACKGROUND: Transient production of gamma-retroviruses, including self
      inactivating (SIN) retroviruses, is a common method for rapidly generating virus
      capable of gene delivery. Stable (continuous) production of virus is preferable
      to transient production for clinical and biotechnology purposes, however, because
      it allows for significant quantities of a uniform virus to be generated over a
      prolonged period of time, thus allowing for longitudinal functional studies and
      quality analysis. Unfortunately, stable production of SIN retroviruses is
      difficult to achieve. RESULTS: We describe a novel method to rapidly and cost
      effectively create packaging cells capable of continuously producing self
      inactivating gamma-retroviruses. We imbedded the SIN proviral construct into a
      minimal piggyBac transposon vector and then integrated the hybrid vector into
      packaging cells that already stably expressed the viral gag-pro-pol and envelope
      genes. Cells that stably produced self-inactivating gamma-retroviruses could be
      identified (and purified) as early as 3 weeks after initial transfection; these
      cells produced virus for at least 9 weeks without a decline in titer.
      CONCLUSIONS: This viral-minimal piggyBac hybrid vector allowed for the rapid
      generation and purification of packaging cells capable of stably producing self
      inactivated gamma-retroviruses. This method can be applied to the large-scale
      production of viruses for use in research, biotechnology, and potentially,
      clinical trials.

PMID- 26306623
TI  - Comparison of Hi-C results using in-solution versus in-nucleus ligation.
AB  - BACKGROUND: Chromosome conformation capture and various derivative methods such
      as 4C, 5C and Hi-C have emerged as standard tools to analyze the three
      dimensional organization of the genome in the nucleus. These methods employ
      ligation of diluted cross-linked chromatin complexes, intended to favor proximity
      dependent, intra-complex ligation. During development of single-cell Hi-C, we
      devised an alternative Hi-C protocol with ligation in preserved nuclei rather
      than in solution. Here we directly compare Hi-C methods employing in-nucleus
      ligation with the standard in-solution ligation. RESULTS: We show in-nucleus
      ligation results in consistently lower levels of inter-chromosomal contacts.
      Through chromatin mixing experiments we show that a significantly large fraction
      of inter-chromosomal contacts are the result of spurious ligation events formed
      during in-solution ligation. In-nucleus ligation significantly reduces this
      source of experimental noise, and results in improved reproducibility between
      replicates. We also find that in-nucleus ligation eliminates restriction fragment
      length bias found with in-solution ligation. These improvements result in greater
      reproducibility of long-range intra-chromosomal and inter-chromosomal contacts,
      as well as enhanced detection of structural features such as topologically
      associated domain boundaries. CONCLUSIONS: We conclude that in-nucleus ligation
      captures chromatin interactions more consistently over a wider range of
      distances, and significantly reduces both experimental noise and bias. In-nucleus
      ligation creates higher quality Hi-C libraries while simplifying the experimental
      procedure. We suggest that the entire range of 3C applications are likely to show
      similar benefits from in-nucleus ligation.

PMID- 26306624
TI  - The natural compound forskolin synergizes with dexamethasone to induce cell death
      in myeloma cells via BIM.
AB  - We have previously demonstrated that activation of the cyclic adenosine
      monophosphate (cAMP) pathway kills multiple myeloma (MM) cells both in vitro and
      in vivo. In the present study we have investigated the potential of enhancing the
      killing of MM cell lines and primary MM cells by combining the cAMP-elevating
      compound forskolin with the commonly used MM therapeutic drugs melphalan,
      cyclophosphamide, doxorubicin, bortezomib and dexamethasone. We observed that
      forskolin potentiated the killing induced by all the tested agents as compared to
      treatment with the single agents alone. In particular, forskolin had a
      synergistic effect on the dexamethasone-responsive cell lines H929 and OM-2. By
      knocking down the proapoptotic BCL-2 family member BIM, we proved this protein to
      be involved in the synergistic induction of apoptosis by dexamethasone and
      forskolin. The ability of forskolin to maintain the killing of MM cells even at
      lower concentrations of the conventional agents suggests that forskolin may be
      used to diminish treatment-associated side effects. Our findings support a
      potential role of forskolin in combination with current conventional agents in
      the treatment of MM. 

PMID- 26306625
TI  - Efficacy of high-dose rosuvastatin preloading in patients undergoing percutaneous
      coronary intervention: a meta-analysis of fourteen randomized controlled trials.
AB  - BACKGROUND: Numerous studies have evidenced that statins can reduce the incidence
      of cardiovascular disease. However, the effects of high-dose rosuvastatin (RSV)
      preloading in patients undergoing percutaneous coronary intervention (PCI) are
      controversial. OBJECTIVE: We attempted to identify and quantify the potential
      cardioprotective benefits of high-dose RSV preloading on final thrombolysis in
      myocardial infarction (TIMI) flow grade, major adverse cardiac events (MACE), and
      peri-procedural myocardial injury (PMI) in patients undergoing PCI. METHODS:
      Pubmed, EMBASE, Cochrane Central Register of Controlled Trials and ISI Web of
      Science databases were systematically searched for randomized controlled trials
      (RCTs) up to June 2015. We assessed the incidence of MACE and PMI in all enrolled
      patients for subgroups stratified by clinical presentation and previous statin
      therapy during the follow-up period. RESULTS: Fourteen trials with 3368
      individuals were included in our meta-analysis. High-dose RSV preloading before
      PCI lead to a 58 % reduction in MACE (odds ratio [OR] = 0.42, 95 % confidence
      intervals [CI]: 0.29-0.61, P < 0.00001) and a 60 % reduction in PMI (OR = 0.40,
      95 % CI: 0.25-0.63, P < 0.0001). This procedure also improved the final TIMI flow
      grade in patients undergoing PCI (OR = 1.61, 95 % CI: 1.09-2.38, P = 0.02). The
      benefits on MACE were significant for both stable angina patients (OR = 0.42, 95
      % CI: 0.21-0.87, P = 0.02) and acute coronary syndrome (ACS) patients (OR = 0.42,
      95 % CI: 0.27-0.65, P < 0.0001); and for both statin naive patients (OR = 0.42,
      95 % CI: 0.28-0.64, P < 0.0001) and previous statin therapy patients (OR = 0.28,
      95 % CI: 0.10-0.73, P = 0.01). CONCLUSION: High-dose RSV preloading can
      significantly improve myocardial perfusion and reduce both MACE and PMI in
      patients undergoing PCI. The cardioprotective benefits of RSV preloading were
      significant in not only stable angina and ACS patients but also statin naive and
      previous statin therapy patients. The cardioprotective benefits of RSV preloading
      in the follow-up period mainly resulted from a reduction in spontaneous MI and
      TVR, especially for ACS and statin naive patients.

PMID- 26306626
TI  - Natural Products for Management of Oral Mucositis Induced by Radiotherapy and
      Chemotherapy.
AB  - Oral mucositis is a common side effect of systemic chemotherapy and radiotherapy
      of head and neck in patients with cancer. Severe oral mucositis is painful and
      affects oral functions, including intake of food and medications and speech.
      Prevention of oral mucositis affects the life quality of patients. Recent studies
      have been focused on natural products to improve or reduce this complication.
      Many clinical trials have been performed to assess natural products for treatment
      of mucositis and their results are promising. The authors reviewed the evidence
      for natural products in the prevention and treatment of oral mucositis induced by
      radiation therapy and chemotherapy. 

PMID- 26306627
TI  - Urinary pyridinoline cross-links as biomarkers of osteogenesis imperfecta.
AB  - Osteogenesis imperfecta (OI) is a group of genetic heterogeneous connective
      tissue disorders characterized by increased bone fragility and susceptibility to
      fractures. Laboratory diagnosis relies on time-consuming and cost-intensive
      biochemical and molecular genetics analyses. Therefore, it is desirable to
      identify and establish new diagnostic markers for OI that are reliable, cost
      effective and easily accessible. In our study we have identified the ratio of the
      urinary pyridinoline cross-links lysyl-pyridinoline and hydroxylysyl-pyridinoline
      as a promising, time- and cost-effective biomarker for osteogenesis imperfecta,
      that could be used furthermore to investigate cases of suspected non-accidental
      injury in infants. 

PMID- 26306628
TI  - De novo transcriptome assembly and analysis to identify potential gene targets
      for RNAi-mediated control of the tomato leafminer (Tuta absoluta).
AB  - BACKGROUND: Providing double-stranded RNA (dsRNA) to insects has been proven to
      silence target genes, and this approach has emerged as a potential method to
      control agricultural pests by engineering plants to express insect dsRNAs. A
      critical step of this technology is the screening of effective target genes
      essential for insect development and/or survival. The tomato leafminer (Tuta
      absoluta Meyrick) is a major Solanum lycopersicum (tomato) pest that causes
      significant yield losses and has recently invaded Europe, from where it is
      spreading at an alarming rate. To explore RNA interference (RNAi) against T.
      absoluta, sequence information on potential target genes is necessary, but only a
      few sequences are available in public databases. RESULTS: We sequenced six
      libraries from RNA samples from eggs, adults, and larvae at four stages,
      obtaining an overall total of around 245 million reads. The assembled T. absoluta
      transcriptome contained 93,477 contigs with an average size of 1,574 bp, 59.8 %
      of which presented positive Blast hits, with 19,995 (21.4 %) annotated by gene
      ontology. From the transcriptome, most of the core genes of the RNAi mechanism of
      Lepidoptera were identified indicating the potential suitability of T. absoluta
      for gene silencing. No contigs displayed significant similarity with a RNA
      dependent RNA Polymerase. Genes from the juvenile hormone and ecdysteroid
      biosynthetic pathways were identified, representing potential target genes for
      systemic silencing. Comparisons of transcript profiles among stages revealed
      1,577 genes differentially expressed at earlier larval stages, from which
      potential gene targets were identified. Five of these genes were evaluated using
      in vitro transcribed dsRNA absorbed by tomato leaflets, which were fed to 1(st)
      instar T. absoluta larvae, resulting in significant reduction of larval body
      weight while exhibiting significant knockdown for three of the genes.
      CONCLUSIONS: The transcriptome we generated represents a valuable genomic
      resource for screening potential gene targets that affect the development or
      survival of T. absoluta larvae. Five novel genes that showed greater expression
      at the 1(st) larval stage were demonstrated to be effective potential RNAi
      targets by reducing larval weight and can be considered good candidates for use
      in RNAi-mediated crop protection.

PMID- 26306629
TI  - Improving clinical trial design for Duchenne muscular dystrophy.
AB  - BACKGROUND: Currently, the most promising therapies for Duchenne muscular
      dystrophy (DMD) are exon skipping and stop codon read-through, two strategies
      aimed at restoring the expression of dystrophin. A phase 3 clinical trial with
      drisapersen, a drug designed to induce exon 51-skipping, has failed to show
      significant improvement of the primary outcome measure, the six-minute walk test.
      DISCUSSION: Here, we review some key points that should be considered when
      designing clinical trials for these new therapies. First, younger patients have
      more functional abilities and more muscle fibers to preserve than older patients
      and therefore are better subjects for trials designed to demonstrate the success
      of new treatments. Second, the inclusion of patients on corticosteroids both in
      the treatment and placebo groups is of concern because the positive effect of
      corticosteroids might mask the effect of the treatment being tested.
      Additionally, the reasonable expectation from these therapies is the slowing of
      disease progression rather than improvement. Therefore, the appropriate clinical
      endpoints are the prolongation of the ability to stand from the floor, climb
      stairs, and walk, not an increase in muscle strength or function. Hence, the time
      frames for the detection of new dystrophin, which occurs within months, and the
      ability to demonstrate a slowing of disease progression, which requires years,
      are strikingly different. Finally, placebo-controlled trials are difficult to
      manage if years of blindness are required to demonstrate a slowing of disease
      progression. Thus, accelerated/conditional approval for new therapies should be
      based on surrogate biochemical outcomes: the demonstration of de novo dystrophin
      production and of its beneficial effect on the functional recovery of muscle
      fiber. These data suggest that clinical trials for DMD patients must be adapted
      to the particular characteristics of the disease in order to demonstrate the
      expected positive effect of new treatments.

PMID- 26306630
TI  - Ryozo Omoto, 1934-2015.

PMID- 26306631
TI  - Unusual cystic hamartomatous lung lesion with clinical manifestation of
      subpleural bullae in a woman of reproductive age: A case report.
AB  - Pulmonary hamartoma is a common benign lung disorder, and most cases show solid
      nodules. Here, we documented the clinicopathological features of a growing, bulla
      like, multilocular hamartomatous lung lesion in a woman of reproductive age. To
      the best of our knowledge, this disorder has not been reported in the literature
      to date. An asymptomatic 29-year-old Japanese woman with no significant past
      medical history was referred to our institution for surgical treatment of a
      bullous lesion in the right upper lobe because the pulmonary lesion had enlarged
      to multilocular cysts, including a giant bulla, within 1 year, leading to
      compression of the right lung. The bullous lesion, which was projected from the
      apex of the lung via a narrow stalk, showed nonemphysematous, multiloculated
      tissue. The wall mimicked a bronchiolar structure with ciliated, nonatypical
      epithelium and layers of nonatypical spindle cells that were positive for smooth
      muscle markers and sex steroid hormone receptors. No cartilage was included in
      the lesion. We believe that this may be a novel form of hamartoma. This disorder
      may be included in a differential diagnosis of subpleural bullous diseases in
      women of reproductive age. 

PMID- 26306632
TI  - Natural Products based P-glycoprotein Activators for Improved beta-amyloid
      Clearance in Alzheimer's Disease: An in silico Approach.
AB  - Alzheimer's disease is an age related disorder and is defined to be progressive,
      irreversible neurodegenerative disease. The potential targets which are
      associated with the Alzheimer's disease are cholinesterases, N-methyl-D-aspartate
      receptor, Beta secretase 1, Pregnane X receptor (PXR) and P-glycoprotein (Pgp). P
      glycoprotein is a member of the ATP binding cassette (ABC) transporter family,
      which is an important integral of the blood-brain, blood-cerebrospinal fluid and
      the blood-testis barrier. Reports from the literature provide evidences that the
      up-regulation of the efflux pump is liable for a decrease in beta -amyloid
      intracellular accumulation and is an important hallmark in Alzheimer's disease
      (AD). Thus, targeting beta-amyloid clearance by stimulating Pgp could be a useful
      strategy to prevent Alzheimer's advancement. Currently available drugs provide
      limited effectiveness and do not assure to cure Alzheimer's disease completely.
      On the other hand, the current research is now directed towards the development
      of synthetic or natural based therapeutics which can delay the onset or
      progression of Alzheimer's disease. Since ancient time medicinal plants such as
      Withania somnifera, Bacopa monieri, Nerium indicum have been used to prevent
      neurological disorders including Alzheimer's disease. Till today around 125
      Indian medicinal plants have been screened on the basis of ethnopharmacology for
      their activity against neurological disorders. In this paper, we report
      bioactives from natural sources which show binding affinity towards the Pgp
      receptor using ligand based pharmacophore development, virtual screening,
      molecular docking and molecular dynamics simulation studies for the bioactives
      possessing acceptable ADME properties. These bioactives can thus be useful to
      treat Alzheimer's disease. 

PMID- 26306633
TI  - Sialylation potentials of the silkworm, Bombyx mori; B. mori possesses an active
      alpha2,6-sialyltransferase.
AB  - N-Glycosylation is an important post-translational modification in most secreted
      and membrane-bound proteins in eukaryotic cells. However, the insect N
      glycosylation pathway and the potentials contributing to the N-glycan synthesis
      are still unclear because most of the studies on these subjects have focused on
      mammals and plants. Here, we identified Bombyx mori sialyltransferase (BmST),
      which is a Golgi-localized glycosyltransferase and which can modify N-glycans.
      BmST was ubiquitously expressed in different organs and in various stages of
      development and localized at the Golgi. Biochemical analysis using Sf9-expressed
      BmST revealed that BmST encoded alpha2,6-sialyltransferase and transferred N
      acetylneuraminic acid (NeuAc) to the nonreducing terminus of Galbeta1-R, but
      exhibited the highest activity toward GalNAcbeta1,4-GlcNAc-R. Unlike human
      alpha2,6-sialyltransferase, BmST required the post-translational modification,
      especially N-glycosylation, for its full activity. N-Glycoprotein analysis of B.
      mori fifth instar larvae revealed that high-mannose-type structure was
      predominant and GlcNAc-linked and fucosylated structures were observed but
      endogenous galactosyl-, N-acetylgalactosaminyl- and sialyl-N-glycoproteins were
      undetectable under the standard analytical approach. These results indicate that
      B. mori genome encodes an alpha2,6-sialyltransferase, but further investigations
      of the sialylation potentials are necessary. 

PMID- 26306634
TI  - Structural determinants of heparin-transforming growth factor-beta1 interactions
      and their effects on signaling.
AB  - Transforming growth factor-beta1 (TGF-beta1, Uniprot: P01137) is a heparin
      binding protein that has been implicated in a number of physiological processes,
      including the initiation of chondrogenesis by human mesenchymal stem cells
      (hMSCs). Here, we identify the molecular features in the protein and in heparin
      required for binding and their effects on the potentiation of TGF-beta1's
      activity on hMSCs. Using a proteomics "Protect and Label" approach, lysines K291,
      K304, K309, K315, K338, K373, K375 and K388 were identified as being directly
      involved in binding heparin (Data are available via ProteomeXchange with
      identifier PXD002772). Competition assays in an optical biosensor demonstrated
      that TGF-beta1 does require N- and 6-O-sulfate groups for binding but that 2-O
      sulfate groups are unlikely to underpin the interaction. Heparin-derived
      oligosaccharides as short as degree of polymerization (dp) 4 have a weak ability
      to compete for TGF-beta1 binding to heparin, which increases with the length of
      the oligosaccharide to reach a maximum between dp18 and dp24. In cell-based
      assays, heparin, 2-O-, 6-O- and N-desulfated re-N-acetylated heparin and
      oligosaccharides 14-24 saccharides (dp14-24) in length all increased the
      phosphorylation of mothers against decapentaplegic homolog 2 (SMAD2) after 6 h of
      stimulation with TGF-beta1. The results provide the structural basis for a model
      of heparin/heparan sulfate binding to TGF-beta1 and demonstrate that the features
      in the polysaccharide required for binding are not identical to those required
      for sustaining the signaling by TGF-beta1 in hMSCs. 

PMID- 26306635
TI  - Characterization of an N-acetylglucosaminyltransferase involved in Aspergillus
      fumigatus zwitterionic glycoinositolphosphoceramide biosynthesis.
AB  - Glycoinositolphosphoceramides (GIPCs) are complex sphingolipids present at the
      plasma membrane of various eukaryotes with the important exception of mammals. In
      fungi, these glycosphingolipids commonly contain an alpha-mannose residue (Man)
      linked at position 2 of the inositol. However, several pathogenic fungi
      additionally synthesize zwitterionic GIPCs carrying an alpha-glucosamine residue
      (GlcN) at this position. In the human pathogen Aspergillus fumigatus, the
      GlcNalpha1,2IPC core (where IPC is inositolphosphoceramide) is elongated to
      Manalpha1,3Manalpha1,6GlcNalpha1,2IPC, which is the most abundant GIPC
      synthesized by this fungus. In this study, we identified an A. fumigatus N
      acetylglucosaminyltransferase, named GntA, and demonstrate its involvement in the
      initiation of zwitterionic GIPC biosynthesis. Targeted deletion of the gene
      encoding GntA in A. fumigatus resulted in complete absence of zwitterionic GIPC;
      a phenotype that could be reverted by episomal expression of GntA in the mutant.
      The N-acetylhexosaminyltransferase activity of GntA was substantiated by
      production of N-acetylhexosamine-IPC in the yeast Saccharomyces cerevisiae upon
      GntA expression. Using an in vitro assay, GntA was furthermore shown to use UDP-N
      acetylglucosamine as donor substrate to generate a glycolipid product resistant
      to saponification and to digestion by phosphatidylinositol-phospholipase C as
      expected for GlcNAcalpha1,2IPC. Finally, as the enzymes involved in mannosylation
      of IPC, GntA was localized to the Golgi apparatus, the site of IPC synthesis. 

PMID- 26306636
TI  - Automated N-glycan profiling of a mutant Trypanosoma rangeli sialidase expressed
      in Pichia pastoris, using tandem mass spectrometry and bioinformatics.
AB  - A mutant Trypanosoma rangeli sialidase, Tr7, expressed in Pichia pastoris,
      exhibits significant trans-sialidase activity, and has been used for analytical
      scale production of sialylated human milk oligosaccharides. Mass spectrometry
      based site-specific N-glycoprofiling of Tr7 showed that heterogeneous high
      mannose type N-glycans were present at all the five potential N-linked
      glycosites. N-linked glycans in Tr7 were predominantly neutral oligosaccharides
      with compositions Man(8-16)GlcNA(c2), but also mono- and di-phosphorylated
      oligosaccharides in the forms of Man(9-15)P(1)GlcNA(c2) and Man(9
      14)P(2)GlcNA(c2), respectively. Some phosphorylated N-linked glycans further
      contained an additional HexNAc, which has not previously been reported in P.
      pastoris-expressed proteins. We compiled a method pipeline that combined
      hydrophilic interaction liquid chromatography enrichment of glycopeptides, high
      accuracy mass spectrometry and automated interpretation of the mass spectra with
      in-house developed "MassAI" software, which proved efficient in glycan site
      microheterogeneity analysis. Functional analysis showed that the deglycosylated
      Tr7 retained more than 90% of both the sialidase and trans-sialidase activities
      relative to the glycosylated Tr7.

PMID- 26306637
TI  - Optimal sequencing of docetaxel and abiraterone in men with metastatic castration
      resistant prostate cancer.
AB  - BACKGROUND: Recent advances have yielded multiple new life-prolonging treatments
      for men with metastatic castration-resistant prostate cancer (mCRPC) including
      chemotherapy, next-generation hormonal therapy, immunotherapy, and
      radiopharmaceutical products. However, the optimal sequencing of these agents to
      maximize clinical benefit remains unclear. Recent data from the CHAARTED and
      STAMPEDE studies suggest that early use of docetaxel in men with metastatic
      hormone-sensitive prostate cancer (mHSPC) significantly improves survival, but
      whether early compared with delayed use of chemotherapy also provides a survival
      advantage in mCRPC is unknown. METHODS: A retrospective analysis of consecutive
      mCRPC patients treated at Johns Hopkins is reported. Patients included were
      treated with sequential docetaxel and abiraterone, in either order. The combined
      progression-free survival (combined PFS: PFS1 + PFS2) of abiraterone-to-docetaxel
      is compared to the reverse sequence, where PFS1 and PFS2 represent progression
      free survival on the first and second agents respectively. Overall survival (OS)
      from the start of the first therapy to death is compared between groups. Baseline
      characteristics are reported prior to the start of the first agent in the
      sequence. Propensity score-weighted multivariable models and Kaplan-Meier
      analysis are used for evaluation of the primary and secondary outcomes. RESULTS:
      Fifty-eight patients who began treatment for mCRPC between January 2011 (the year
      of abiraterone's FDA-approval) and February 2015 were identified: 26 were in the
      docetaxel-to-abiraterone group and 32 were in the abiraterone-to-docetaxel group.
      Patients in the abiraterone-to-docetaxel group had more Gleason 8-10 tumors,
      greater metastatic burden in bone, and higher median PSAs than those in the
      docetaxel-to-abiraterone group. Propensity score-weighted univariate analyses for
      combined PFS (HR 0.82; 95%CI 0.50-1.33; P = 0.41) and OS (HR 0.79; 95%CI 0.50
      1.25; P = 0.31) do not identify any significant differences based on treatment
      sequence. Propensity score-weighted multivariate analyses for combined PFS (HR
      0.91; 95%CI 0.52-1.60; P = 0.74) and OS (HR 0.98; 95%CI 0.59-1.63; P = 0.95) also
      do not identify any significant differences between groups. CONCLUSIONS: We do
      not observe differences in clinical outcomes based on alternative sequencing of
      abiraterone and docetaxel in men with mCRPC. Treatment sequencing should be
      determined by patient and disease characteristics, comorbidities and end-organ
      function, ability to tolerate side effects, and patient preferences. Studies
      evaluating biomarkers to inform optimal treatment sequencing in men with mCRPC
      are urgently needed.

PMID- 26306638
TI  - Modulation of protein behavior through light responses of TiO2 nanodots films.
AB  - In this work, the behavior of protein molecules adsorbed on TiO2 nanodots films
      are modulated through the light responses of the nanodots. TiO2 nanodots films
      are first prepared through phase separation induced self assembly. Then, bovine
      serum albumin (BSA) is adsorbed on TiO2 nanodots films and exposed to ultraviolet
      (365 nm) illumination. It is found the conformation of surface-bound BSA
      molecules changes with ultraviolet illumination. Moreover, the BSA molecules
      conjugate to the surface-bound molecules, which are in the overlayer, are
      released. The reason is ascribed to that TiO2 nanodots absorb ultraviolet and
      result in the increase of surface hydroxyl groups on nanodots. Such increase
      further leads to intensified attraction of -NH3 groups in the surface-bound BSA
      molecules. That not only changes the conformation of the surface-bound BSA
      molecules, but also weaken the conjugation between surface-bound molecules and
      other BSA molecules in the overlayer. Eventually, the overlayer of BSA molecules
      is released. It is believed that such protein conformation variation and release
      behavior induced through light responses of TiO2 nanodots are crucial in
      understanding the biomedical performance of TiO2 nanostructures. Also, it could
      be widely utilized in tailoring of the materials-protein interactions. 

PMID- 26306639
TI  - Indoor location-aware medical systems for smart homecare and telehealth
      monitoring: state-of-the-art.
AB  - This paper presents a comprehensive literature review of current progress in the
      application of state-of-the-art indoor positioning systems for telecare and
      telehealth monitoring. This review is the first in the literature that provides a
      comprehensive discussion on how existing wireless indoor positioning systems can
      benefit the development of home-based care systems. More specifically, this
      review provides an in-depth comparative study of how both system users and
      medical practitioners can get benefit from indoor positioning technologies; e.g.
      for real-time monitoring of patients suffering chronic cardiovascular conditions,
      general monitoring of activities of daily living (ADLs), fall detection systems
      for the elderly as well as indoor navigation systems for those suffering from
      visual impairments. Furthermore, it also details various aspects worth
      considering when choosing a certain technology for a specific healthcare
      application; e.g. the spatial precision demanded by the application, trade-offs
      between unobtrusiveness and complexity, and issues surrounding compliance and
      adherence with the use of wearable tags. Beyond the current state-of-the-art,
      this review also rigorously discusses several research opportunities and the
      challenges associated with each. 

PMID- 26306641
TI  - Refined phylogenetic structure of an abundant East Asian Y-chromosomal haplogroup
      O*-M134.
AB  - The human Y-chromosome haplogroup O-M134 is one of the most abundant paternal
      lineages in East Asian populations, comprising ~13% of Han Chinese males, and
      also common in Kazakh, Korean, Japanese, Thai and so on. Despite its considerable
      prevalence, its current substructure is poorly resolved with only one downstream
      marker (M117) previously investigated. Here we address this deficiency by
      investigating some single-nucleotide polymorphisms (SNPs) previously reported
      being potentially associated with O-M134 based on high-throughput DNA-sequencing
      data. Using a panel of 1301 Chinese males we first identified 154 haplogroup O
      M134 subjects. We then investigated the phylogenetic structure within this
      haplogroup using 10 SNPs (F444, F629, F3451, F46, F48, F209, F2887, F3386, F1739
      and F152). Two major branches were identified, O-M117 and O-F444 and the latter
      was further divided into two main subclades, O-F629 and O-F3451, accounting for
      10.84 and 0.92% of the Han Chinese, respectively. This update of O-M134
      diversification permits better resolution of male lineages in population studies
      of East Asia. 

PMID- 26306640
TI  - Reinitiation of mRNA translation in a patient with X-linked infantile spasms with
      a protein-truncating variant in ARX.
AB  - Mutations in the Aristaless-related homeobox gene (ARX) lead to a range of X
      linked intellectual disability phenotypes, with truncating variants generally
      resulting in severe X-linked lissencephaly with ambiguous genitalia (XLAG), and
      polyalanine expansions and missense variants resulting in infantile spasms. We
      report two male patients with early-onset infantile spasms in whom a novel
      c.34G>T (p.(E12*)) variant was identified in the ARX gene. A similar variant
      c.81C>G (p.(Y27*)), has previously been described in two affected cousins with
      early-onset infantile spasms, leading to reinitiation of ARX mRNA translation
      resulting in an N-terminal truncated protein. We show that the novel c.34G>T
      (p.(E12*)) variant also reinitiated mRNA translation at the next AUG codon (c.121
      123 (p.M41)), producing the same N-terminally truncated protein. The production
      of both of these truncated proteins was demonstrated to be at markedly reduced
      levels using in vitro cell assays. Using luciferase reporter assays, we
      demonstrate that transcriptional repression capacity of ARX was diminished by
      both the loss of the N-terminal corepressor octapeptide domain, as a consequence
      of truncation, and the marked reduction in mutant protein expression. Our study
      indicates that premature termination mutations very early in ARX lead to
      reinitiation of translation to produce N-terminally truncated protein at markedly
      reduced levels of expression. We conclude that even low levels of N-terminally
      truncated ARX is sufficient to improve the patient's phenotype compared with the
      severe phenotype of XLAG that includes malformations of the brain and genitalia
      normally seen in complete loss-of-function mutations in ARX. 

PMID- 26306642
TI  - FAPI: Fast and accurate P-value Imputation for genome-wide association study.
AB  - Imputing individual-level genotypes (or genotype imputation) is now a standard
      procedure in genome-wide association studies (GWAS) to examine disease
      associations at untyped common genetic variants. Meta-analysis of publicly
      available GWAS summary statistics can allow more disease-associated loci to be
      discovered, but these data are usually provided for various variant sets. Thus
      imputing these summary statistics of different variant sets into a common
      reference panel for meta-analyses is impossible using traditional genotype
      imputation methods. Here we develop a fast and accurate P-value imputation (FAPI)
      method that utilizes summary statistics of common variants only. Its
      computational cost is linear with the number of untyped variants and has similar
      accuracy compared with IMPUTE2 with prephasing, one of the leading methods in
      genotype imputation. In addition, based on the FAPI idea, we develop a metric to
      detect abnormal association at a variant and showed that it had a significantly
      greater power compared with LD-PAC, a method that quantifies the evidence of
      spurious associations based on likelihood ratio. Our method is implemented in a
      user-friendly software tool, which is available at
      http://statgenpro.psychiatry.hku.hk/fapi. 

PMID- 26306644
TI  - Children with sex chromosome trisomies: parental disclosure of genetic status.
AB  - Sex chromosome trisomies (SCTs) are frequently diagnosed, both prenatally and
      postnatally, but the highly variable childhood outcomes can leave parents at a
      loss on whether, when and how to disclose genetic status. In two complementary
      studies, we detail current parental practices, with a view to informing parents
      and their clinicians. Study 1 surveyed detailed qualitative data from focus
      groups of parents and affected young people with either Trisomy X or XYY (N=34
      families). These data suggested that decisions to disclose were principally
      affected by the child's level of cognitive, social and emotional functioning.
      Parents reported that they were more likely to disclose when a child was
      experiencing difficulties. In Study 2, standardised data on cognitive, social and
      emotional outcomes in 126 children with an SCT and 63 sibling controls
      highlighted results that converged with Study 1: logistic regression analyses
      revealed that children with the lowest levels of functioning were more likely to
      know about their SCT than those children functioning at a higher level. These
      effects were also reflected in the likelihood of parents to disclose to
      unaffected siblings, schools and general practitioners. In contrast, specific
      trisomy type and the professional category of the clinician providing the
      original diagnosis did not affect likelihood of disclosure. Our study emphasises
      the complex weighing up of costs and benefits that parents engage in when
      deciding whether to disclose a diagnosis. 

PMID- 26306643
TI  - Harmonising and linking biomedical and clinical data across disparate data
      archives to enable integrative cross-biobank research.
AB  - A wealth of biospecimen samples are stored in modern globally distributed
      biobanks. Biomedical researchers worldwide need to be able to combine the
      available resources to improve the power of large-scale studies. A prerequisite
      for this effort is to be able to search and access phenotypic, clinical and other
      information about samples that are currently stored at biobanks in an integrated
      manner. However, privacy issues together with heterogeneous information systems
      and the lack of agreed-upon vocabularies have made specimen searching across
      multiple biobanks extremely challenging. We describe three case studies where we
      have linked samples and sample descriptions in order to facilitate global
      searching of available samples for research. The use cases include the ENGAGE
      (European Network for Genetic and Genomic Epidemiology) consortium comprising at
      least 39 cohorts, the SUMMIT (surrogate markers for micro- and macro-vascular
      hard endpoints for innovative diabetes tools) consortium and a pilot for data
      integration between a Swedish clinical health registry and a biobank. We used the
      Sample avAILability (SAIL) method for data linking: first, created harmonised
      variables and then annotated and made searchable information on the number of
      specimens available in individual biobanks for various phenotypic categories. By
      operating on this categorised availability data we sidestep many obstacles
      related to privacy that arise when handling real values and show that harmonised
      and annotated records about data availability across disparate biomedical
      archives provide a key methodological advance in pre-analysis exchange of
      information between biobanks, that is, during the project planning phase. 

PMID- 26306645
TI  - Mothers' psychological adaptation to Duchenne/Becker muscular dystrophy.
AB  - Duchenne and Becker muscular dystrophy (DBMD) cause significant emotional and
      care-related burden on caregivers, but no studies have evaluated predictors of
      positive caregiver outcomes, including disorder-specific psychological
      adaptation. Using a community-engaged approach focused on supporting mothers in
      positive aspects of caregiving, this prospective study aims to assess (i) the
      association between child's baseline functional status and mothers' illness
      perceptions, resilience, and coping self-efficacy; and (ii) predictors of
      mothers' psychological adaptation to caring for a child with DBMD. Biological
      mothers with at least one living child with DBMD completed a baseline survey
      (n=205) with 1-year (n=147) and 2-year (n=144) follow-up surveys. Worse child's
      baseline function was associated not only with increased caregiver burden and
      reduced maternal resilience, but also with perception of positive disease impact
      on the family. At two follow-ups, increased psychological adaptation to DBMD was
      predicted by resilience (beta=0.264, P=0.001) and perceived positive impact
      (beta=0.310, P<0.001), controlling for mother's age (beta=-0.305, P<0.001) and
      income (beta=-0.088, P=0.245). Child's functional status and caregiver burden of
      DBMD did not predict DBMD-specific adaptation. Though clinicians caring for
      families with DBMD should anticipate increased caregiver burden as the disorder
      progresses, interventions focused on caregiver burden are not expected to
      influence mothers' psychosocial adaptation. Efforts to improve mothers' well
      being should focus on fostering mothers' resilience and enhancing perceptions of
      positive disease impact (benefit finding). Results suggest that psychosocial
      interventions can highlight strengths and well-being rather than burden and
      deficit. 

PMID- 26306647
TI  - Defining the role of the CGGBP1 protein in FMR1 gene expression.
AB  - Fragile X syndrome is the most common heritable form of intellectual disability
      and is caused by the expansion over 200 repeats and subsequent methylation of the
      CGG triplets at the 5' UTR of the FMR1 gene, leading to its silencing. The
      epigenetic and molecular mechanisms responsible for FMR1 gene silencing are not
      fully clarified. To identify structure-specific proteins that could recruit
      components of the silencing machinery we investigated the role of CGGBP1 in FMR1
      gene transcription. CGGBP1 is a highly conserved protein that binds specifically
      to unmethylated CGG tracts. Its role on FMR1 transcription is yet to be defined.
      Sequencing analysis and expression studies through quantitative PCR of CGGBP1
      were performed in cell lines with different allele expansions: wild type,
      premutation, methylated full mutation and unmethylated full mutation,
      demonstrating no differences between them. ChIP assays clearly demonstrated that
      CGGBP1 binds to unmethylated CGG triplets of the FMR1 gene, but not to methylated
      CGGs. We also observed that CGGBP1 binding to the FMR1 locus was restored after
      pharmacological demethylation, with 5-azadC, of alleles, carriers of methylated
      full mutation, suggesting a possible role for CGGBP1 in FMR1 expression. CGGBP1
      silencing with shRNAs (reaching ~98% of CGGBP1-mRNA depletion) did not affect
      FMR1 transcription and CGG expansion stability in expanded alleles. Although the
      strong binding to the CGG tract could suggest a relevant role of CGGBP1 on FMR1
      gene expression, our results demonstrate that CGGBP1 has no direct effect on FMR1
      transcription and CGG repeat stability. 

PMID- 26306649
TI  - Approaches to the management of bipolar disorder: past, present and future.

PMID- 26306648
TI  - Judging adaptive management practices of U.S. agencies.
AB  - All U.S. federal agencies administering environmental laws purport to practice
      adaptive management (AM), but little is known about how they actually implement
      this conservation tool. A gap between the theory and practice of AM is revealed
      in judicial decisions reviewing agency adaptive management plans. We analyzed all
      U.S. federal court opinions published through 1 January 2015 to identify the
      agency AM practices courts found most deficient. The shortcomings included lack
      of clear objectives and processes, monitoring thresholds, and defined actions
      triggered by thresholds. This trio of agency shortcuts around critical, iterative
      steps characterizes what we call AM-lite. Passive AM differs from active AM in
      its relative lack of management interventions through experimental strategies. In
      contrast, AM-lite is a distinctive form of passive AM that fails to provide for
      the iterative steps necessary to learn from management. Courts have developed a
      sophisticated understanding of AM and often offer instructive rather than merely
      critical opinions. The role of the judiciary is limited by agency discretion
      under U.S. administrative law. But courts have overturned some agency AM-lite
      practices and insisted on more rigorous analyses to ensure that the promised
      benefits of structured learning and fine-tuned management have a reasonable
      likelihood of occurring. Nonetheless, there remains a mismatch in U.S.
      administrative law between the flexibility demanded by adaptive management and
      the legal objectives of transparency, public participation, and finality. 

PMID- 26306646
TI  - The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31
      microdeletion versus a KANSL1 sequence variant.
AB  - The Koolen-de Vries syndrome (KdVS; OMIM #610443), also known as the 17q21.31
      microdeletion syndrome, is a clinically heterogeneous disorder characterised by
      (neonatal) hypotonia, developmental delay, moderate intellectual disability, and
      characteristic facial dysmorphism. Expressive language development is
      particularly impaired compared with receptive language or motor skills. Other
      frequently reported features include social and friendly behaviour, epilepsy,
      musculoskeletal anomalies, congenital heart defects, urogenital malformations,
      and ectodermal anomalies. The syndrome is caused by a truncating variant in the
      KAT8 regulatory NSL complex unit 1 (KANSL1) gene or by a 17q21.31 microdeletion
      encompassing KANSL1. Herein we describe a novel cohort of 45 individuals with
      KdVS of whom 33 have a 17q21.31 microdeletion and 12 a single-nucleotide variant
      (SNV) in KANSL1 (19 males, 26 females; age range 7 months to 50 years). We
      provide guidance about the potential pitfalls in the laboratory testing and
      emphasise the challenges of KANSL1 variant calling and DNA copy number analysis
      in the complex 17q21.31 region. Moreover, we present detailed phenotypic
      information, including neuropsychological features, that contribute to the broad
      phenotypic spectrum of the syndrome. Comparison of the phenotype of both the
      microdeletion and SNV patients does not show differences of clinical importance,
      stressing that haploinsufficiency of KANSL1 is sufficient to cause the full KdVS
      phenotype. 

PMID- 26306650
TI  - Supplementation of antipsychotic treatment with sarcosine - GlyT1 inhibitor -
      causes changes of glutamatergic (1)NMR spectroscopy parameters in the left
      hippocampus in patients with stable schizophrenia.
AB  - Glutamatergic system, the main stimulating system of the brain, plays an
      important role in the pathogenesis of schizophrenia. Hippocampus, a structure
      crucial for memory and cognitive functions and rich in glutamatergic neurons, is
      a natural object of interest in studies on psychoses. Sarcosine, a glycine
      transporter (GlyT-1) inhibitor influences the function of NMDA receptor and
      glutamate-dependent transmission. The aim of the study was to assess the effects
      of sarcosine on metabolism parameters in the left hippocampus in patients with
      schizophrenia. Assessments were performed using proton nuclear magnetic resonance
      ((1)H NMR) spectroscopy (1.5T). Fifty patients diagnosed with schizophrenia (DSM
      IV-TR), with dominant negative symptoms, in stable clinical condition and stable
      antipsychotics doses were treated either with sarcosine (n=25) or placebo (n=25).
      Spectroscopic parameters were evaluated within groups and between two groups
      before and after 6-month intervention. All patients were also assessed with the
      Positive and Negative Syndrome Scale (PANSS). In the sarcosine group, after 6
      month treatment, we found significant decrease in hippocampal Glx/Cr (Glx-complex
      of glutamate, glutamine and GABA, Cr-creatine) and Glx/Cho (Cho-choline), while N
      acetylaspartate (NAA), myo-inositol (mI), Cr and Cho parameters remained stable
      along the study and also did not differ significantly between both groups. This
      is the first study showing that a pharmacological intervention in schizophrenia,
      particularly augmentation of the antypsychotic treatment with sarcosine, may
      reverse the pathological increase in glutamatergic transmission in the
      hippocampus. The results confirm involvement of glutamatergic system in the
      pathogenesis of schizophrenia and demonstrate beneficial effects of GlyT-1
      inhibitor on the metabolism in the hippocampus and symptoms of schizophrenia.

PMID- 26306652
TI  - Cerebral alterations of type 2 diabetes mellitus on MRI: A pilot study.
AB  - This study is to investigate gray matter volume, cortical thickness, and surface
      area of the brain in patients with type 2 diabetes mellitus (T2DM). High
      resolution T1-weighted MR images were obtained from eighteen T2DM and seventeen
      normal controls. All images were processed using our newly developed BrainLab
      toolbox. Declines of gray matter volume, cortical thickness, and surface area
      were found in T2DM patients. Significantly reduced ROIs of gray matter volume
      happened in subcortical gray nuclei (left caudate and right caudate), and
      significantly reduced ROIs of cortical thickness occurred in temporal lobe (left
      superior temporal gyrus), parietal lobe (left angular gyrus), and occipital lobe
      (right superior occipital gyrus, left middle occipital gyrus and right cuneus).
      Apparently reduced ROIs of surface area were mainly distributed in frontal lobe
      (right superior frontal gyrus (dorsal) and left paracentral lobule). The findings
      indicated that T2DM caused brain changes in specific regions. This work revealed
      neural alterations of T2DM, which had a great significance in early diagnosis of
      the disease. 

PMID- 26306651
TI  - Role of orexin A signaling in dietary palmitic acid-activated microglial cells.
AB  - Excess dietary saturated fatty acids such as palmitic acid (PA) induce peripheral
      and hypothalamic inflammation. Hypothalamic inflammation, mediated in part by
      microglial activation, contributes to metabolic dysregulation. In rodents, high
      fat diet-induced microglial activation results in nuclear translocation of
      nuclear factor-kappa B (NFkappaB), and increased central pro-inflammatory
      cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). The
      hypothalamic neuropeptide orexin A (OXA, hypocretin 1) is neuroprotective in
      brain. In cortex, OXA can also reduce inflammation and neurodegeneration through
      a microglial-mediated pathway. Whether hypothalamic orexin neuroprotection
      mechanisms depend upon microglia is unknown. To address this issue, we evaluated
      effects of OXA and PA on inflammatory response in immortalized murine microglial
      and hypothalamic neuronal cell lines. We demonstrate for the first time in
      microglial cells that exposure to PA increases gene expression of orexin-1
      receptor but not orexin-2 receptor. Pro-inflammatory markers IL-6, TNF-alpha, and
      inducible nitric oxide synthase in microglial cells are increased following PA
      exposure, but are reduced by pretreatment with OXA. The anti-inflammatory marker
      arginase-1 is increased by OXA. Finally, we show hypothalamic neurons exposed to
      conditioned media from PA-challenged microglia have increased cell survival only
      when microglia were pretreated with OXA. These data support the concept that OXA
      may act as an immunomodulatory regulator of microglia, reducing pro-inflammatory
      cytokines and increasing anti-inflammatory factors to promote a favorable
      neuronal microenvironment. 

PMID- 26306653
TI  - Evidence for the contribution of BDNF-TrkB signal strength in neurogenesis: An
      organotypic study.
AB  - The importance of neurotrophins, especially brain-derived neurotrophic factor
      (BDNF) in the regulation of mammalian neurogenesis has been extensively studied.
      However, the exact effects of BDNF on cell proliferation and neurogenesis remain
      controversial. Here we tried to use an organotypic hippocampal slice culture
      (OHSC) to precisely control the concentration of BDNF and investigate their
      effects on neuro- and gliogenesis in vitro. With chronic supplementation of
      various concentration of the recombinant BDNF in culture medium, the number of
      newly born neurons was highly increased in a concentration dependent manner,
      while the number of glial cells remained unchanged. Blocking TrkB-BDNF signal
      pathway led to inhibition of neurogenesis. Time series analysis of BDNF and TrkB
      expression revealed relative low levels of BDNF and TrkB expression during early
      culture period, which might account for the results that early BDNF
      supplementation was more effective in the promotion of neurogenesis than late
      supplementation. These observations suggested that appropriate development
      related modulation of BDNF-TrkB signal strength might impact on the initiation
      and maintenance of neurogenesis. 

PMID- 26306654
TI  - Endocrine therapy resistance in breast cancer: current status, possible
      mechanisms and overcoming strategies.
AB  - Endocrine therapy has become one of most effective forms of targeted adjuvant
      therapy for hormone-sensitive breast cancer and may be given after surgery or
      radiotherapy, and also prior, or subsequent to chemotherapy. Current commonly
      used drugs for adjuvant endocrine therapy can be divided into following three
      classes: selective estrogen receptor modulators, aromatase inhibitors and
      selective estrogen receptor downregulators. Tumor cells can develop resistance to
      endocrine therapy, a major obstacle limiting the success of breast cancer
      treatment. The complicated crosstalk, both genomic and nongenomic, between
      estrogen receptors and growth factors was considered to be a crucial factor
      contributing to endocrine resistance. However, resistance to this therapy is
      thought to be a progressive, step-wise process, and the underlying mechanism
      remains unclear. In this review, we summarize the possible biological and
      molecular mechanisms that underlie endocrine resistance, and discuss some novel
      strategies to overcoming these issues. 

PMID- 26306655
TI  - Constituents of PG201 (Layla((r))), a multi-component phytopharmaceutical, with
      inhibitory activity on LPS-induced nitric oxide and prostaglandin E2 productions
      in macrophages.
AB  - Fourteen compounds, coumarin (1), demethylsuberosin (2), xanthotoxin (3),
      psoralen (4), decursinol (5), decursin (6), decursinol angelate (7),
      chikusetsusaponin IVa (8), chikusetsusaponin IVa methyl ester (9), ethyl caffeate
      (10), syringaresinol (11), cnidilide (12), farnesol (13), and linoleic acid (14),
      were isolated from phytopharmaceutical PG201 (Layla((r))) by activity-guided
      fractionation utilizing inhibitory activity on nitric oxide (NO) production in
      vitro. The isolates 1-14 were evaluated for their inhibitory activity on LPS
      induced NO and prostaglandin E2 (PGE2) productions in RAW 264.7 cells. All the
      compounds except 14 displayed suppressive effects on LPS-induced NO and PGE2
      production with IC50 values ranging from 8 to 60 MUM. Among these, compound 10
      showed the most potent inhibitory effect on NO production from RAW 264.7 cells
      with an IC50 value of 8.25 MUM. Compounds 2, 9, and 10 exhibited high inhibitory
      effects on PGE2 production with the IC50 values of 9.42, 7.51, and 6.49 MUM,
      respectively. These findings suggest that compounds 2, 9, and 10 are the
      potential anti-inflammatory active constituents of PG201 and further study may be
      needed to explain their mechanism of action. 

PMID- 26306656
TI  - Calcium is required for ixotrophy of Aureispira sp. CCB-QB1.
AB  - Ixotrophy is a process that enables certain microbes to prey on other cells. The
      ability of cells to aggregate or adhere is thought to be a significant initial
      step in ixotrophy. The gliding, multicellular filamentous bacterium Aureispira
      sp. CCB-QB1 belongs to the family Saprospiraceae and preys on bacteria such as
      Vibrio sp. in seawater. Adhesion and cell aggregation were coincident with
      preying and were hypothesized to play an important role in the ixotrophy in this
      bacterium. To test this hypothesis, experiments to elucidate the mechanisms of
      aggregation or adhesion in this bacterium were performed. The ability of
      Aureispira QB1 to adhere and aggregate to prey bacterium, Vibrio sp., required
      divalent cations, especially calcium ions. In the presence of calcium, Aureispira
      QB1 cells captured 99 % of Vibrio sp. cells after 60 min of incubation. Toluidine
      blue O, which binds acidic polysaccharides, bound to Aureispira QB1 and inhibited
      adhesion of Aureispira QB1. These results suggest that acidic polysaccharides are
      needed for aggregation or adhesion of Aureispira and that calcium ions play a
      significant role in these phenomena.

PMID- 26306657
TI  - Informed decomposition of electroencephalographic data.
AB  - BACKGROUND: Blind source separation techniques have become the de facto standard
      for decomposing electroencephalographic (EEG) data. These methods are poorly
      suited for incorporating prior information into the decomposition process. While
      alternative techniques to this problem, such as the use of constrained
      optimization techniques, have been proposed, these alternative techniques tend to
      only minimally satisfy the prior constraints. In addition, the experimenter must
      preset a number of parameters describing both this minimal limit as well as the
      size of the target subspaces. NEW METHOD: We propose an informed decomposition
      approach that builds upon the constrained optimization approaches for independent
      components analysis to better model and separate distinct subspaces within EEG
      data. We use a likelihood function to adaptively determine the optimal model size
      for each target subspace. RESULTS: Using our method we are able to produce
      ordered independent subspaces that exhibit less residual mixing than those
      obtained with other methods. The results show an improvement in modeling specific
      features of the EEG space, while also showing a simultaneous reduction in the
      number of components needed for each model. COMPARISON WITH EXISTING METHOD(S):
      We first compare our approach to common methods in the field of EEG
      decomposition, such as Infomax, FastICA, PCA, JADE, and SOBI for the task of
      modeling and removing both EOG and EMG artifacts. We then demonstrate the utility
      of our approach for the more complex problem of modeling neural activity.
      CONCLUSIONS: By working in a one-size-fits-all fashion current EEG decomposition
      methods do not adapt to the specifics of each data set and are not well designed
      to incorporate additional information about the decomposition problem. However,
      by adding specific information about the problem to the decomposition task, we
      improve the identification and separation of distinct subspaces within the
      original data and show better preservation of the remaining data.

PMID- 26306658
TI  - The development and test-retest reliability of a method for matching perceived
      location of tinnitus.
AB  - BACKGROUND: A software-based method for assessing and tinnitus in three
      dimensional (3D) 'virtual' auditory space is described and tested. NEW METHOD:
      Phase I was a proof-of-concept evaluation of tinnitus localization in the
      horizontal plane in 19 participants. Phase II assessed the reliability of
      software developed from phase I findings in 34 participants. The software used
      interaural timing and level differences and an average Head Related Transfer
      Function (HRTF) to match tinnitus in the horizontal and vertical plane. The
      reliability of the localization method was assessed across two sessions at least
      1 week apart and compared to the test-retest repeatability of pitch and loudness
      matching using both the new assessment software and a traditional audiometer
      based method. The validity of the method was compared to participants' verbal
      self-reports of tinnitus and their handwritten markings of tinnitus position on
      an image of a head. RESULTS: Participants could localize sound to a position in
      or around the head that was a good match to their self-report of location.
      COMPARISON WITH EXISTING METHOD(S): The method showed test-retest reliability
      (intraclass correlation: azimuth 0.78; elevation 0.37) comparable to matching
      other tinnitus attributes (intraclass correlation: pitch 0.73; loudness 0.48).
      CONCLUSIONS: Tinnitus has a spatial attribute that can be more precisely
      described than "at the ear(s)" or "in the head". The method has important
      ramifications for the assessment and management of tinnitus that make use of the
      spatial representation of sound.

PMID- 26306659
TI  - Evaluation of the macular choroidal thickness using spectral-domain optical
      coherence tomography in patients with obstructive sleep apnoea syndrome:
      response.

PMID- 26306660
TI  - Can low-frequency repetitive transcranial magnetic stimulation precipitate a late
      onset seizure in a stroke patient?

PMID- 26306661
TI  - Setting a research agenda for medical overuse.

PMID- 26306663
TI  - Estimating Adverse Events After Gastrostomy Tube Placement.
AB  - OBJECTIVE: Gastrostomy feeding tube placement in children is associated with a
      high frequency of adverse events. This study sought to preoperatively estimate
      postoperative adverse events in children undergoing gastrostomy feeding tube
      placement. METHODS: This was an observational study of children who underwent
      gastrostomy with or without fundoplication at 1 of 50 participating hospitals,
      using 2011-2013 data from the American College of Surgeons' National Surgical
      Quality Improvement Program Pediatric. The outcome was the occurrence of any
      postoperative complications or mortality at 30 days after gastrostomy tube
      placement. The preoperative clinical characteristics significantly associated
      with occurrence of adverse events were included in a multivariate logistic model.
      The area under the receiver operating characteristic curve was computed to assess
      model performance and split-set validated. RESULTS: A total of 2817 children were
      identified as having undergone gastrostomy tube placement. The unadjusted rate of
      adverse events within 30 days after gastrostomy tube placement was 11%. Thirteen
      predictor variables were identified. Notable preoperative variables associated
      with a greater than 75% increase in adverse event rate were preoperative
      sepsis/septic shock (odds ratio [OR], 10.76, 95% confidence interval [CI], 3.84
      30.17), central nervous system tumor (OR, 3.36; 95% CI, 1.42-7.95), the primary
      procedure as indicated by the current procedural terminology (CPT) linear risk
      variable (OR, 1.93; 95% CI, 1.50-2.49), severe cardiac risk factors (OR, 1.88;
      95% CI, 1.17-3.03), and preoperative seizure history (OR, 1.90; 95% CI, 1.38
      2.62). The area under the receiver operating characteristic curve was 0.71 with
      the derivation data set and 0.71 upon split-set validation. CONCLUSIONS:
      Preoperatively estimating postoperative adverse events in children undergoing
      gastrostomy tube placement is feasible.

PMID- 26306662
TI  - Parental Use of Electronic Cigarettes.
AB  - OBJECTIVE: To describe parental use of electronic cigarettes (e-cigs) to better
      understand the safety risks posed to children. METHODS: Between June 24 and
      November 6, 2014, parents completed a self-administered paper survey during an
      office visit to 15 pediatric practices in a Midwestern practice-based research
      network. Attitudes towards and use of e-cigs are reported for those aware of e
      cigs before the survey. RESULTS: Ninety-five percent (628 of 658) of respondents
      were aware of e-cigs. Of these, 21.0% (130 of 622) had tried e-cigs at least
      once, and 12.3% (77) reported e-cig use by >=1 person in their household (4.0%
      exclusive e-cig use, 8.3% dual use with regular cigarettes). An additional 17.3%
      (109) reported regular cigarette use. Most respondents from e-cig-using homes did
      not think e-cigs were addictive (36.9% minimally or not addictive, 25.0% did not
      know). While 73.7% believed that e-liquid was very dangerous for children if they
      ingested it, only 31.2% believed skin contact to be very dangerous. In 36.1% of e
      cig-using homes, neither childproof caps nor locks were used to prevent
      children's access to e-liquid. Only 15.3% reported their child's pediatrician was
      aware of e-cig use in the home. CONCLUSIONS: E-cig use occurred in 1 in 8 homes,
      often concurrently with regular cigarettes. Many parents who used e-cigs were
      unaware of the potential health and safety hazards, including nicotine poisoning
      for children, and many did not store e-liquid safely. Pediatricians could provide
      education about e-cig associated safety hazards but are unaware of e-cig use in
      their patients' homes.

PMID- 26306665
TI  - Health Estimates Using Survey Raked-Weighting Techniques in an Australian
      Population Health Surveillance System.
AB  - A challenge for population health surveillance systems using telephone
      methodologies is to maintain representative estimates as response rates decrease.
      Raked weighting, rather than conventional poststratification methodologies, has
      been developed to improve representativeness of estimates produced from telephone
      based surveillance systems by incorporating a wider range of sociodemographic
      variables using an iterative proportional fitting process. This study examines
      this alternative weighting methodology with the monthly South Australian
      population health surveillance system report of randomly selected people of all
      ages in 2013 (n = 7,193) using computer-assisted telephone interviewing.
      Poststratification weighting used age groups, sex, and area of residence. Raked
      weights included an additional 6 variables: dwelling status, number of people in
      household, country of birth, marital status, educational level, and highest
      employment status. Most prevalence estimates (e.g., diabetes and asthma) did not
      change when raked weights were applied. Estimates that changed by at least 2
      percentage points (e.g., tobacco smoking and mental health conditions) were
      associated with socioeconomic circumstances, such as dwelling status, which were
      included in the raked-weighting methodology. Raking methodology has overcome, to
      some extent, nonresponse bias associated with the sampling methodology by
      incorporating lower socioeconomic groups and those who are routinely not
      participating in population surveys into the weighting formula. 

PMID- 26306664
TI  - The Influence of Screening for Precancerous Lesions on Family-Based Genetic
      Association Tests: An Example of Colorectal Polyps and Cancer.
AB  - Unintended consequences of secondary prevention include potential introduction of
      bias into epidemiologic studies estimating genotype-disease associations. To
      better understand such bias, we simulated a family-based study of colorectal
      cancer (CRC), which can be prevented by resecting screen-detected polyps. We
      simulated genes related to CRC development through risk of polyps (G1), risk of
      CRC but not polyps (G2), and progression from polyp to CRC (G3). Then, we
      examined 4 analytical strategies for studying diseases subject to secondary
      prevention, comparing the following: 1) CRC cases with all controls, without
      adjusting for polyp history; 2) CRC cases with controls, adjusting for polyp
      history; 3) CRC cases with only polyp-free controls; and 4) cases with either CRC
      or polyps with controls having neither. Strategy 1 yielded estimates of
      association between CRC and each G that were not substantially biased. Strategies
      2-4 yielded biased estimates varying in direction according to analysis strategy
      and gene type. Type I errors were correct, but strategy 1 provided greater power
      for estimating associations with G2 and G3. We also applied each strategy to case
      control data from the Colon Cancer Family Registry (1997-2007). Generally, the
      best analytical option balancing bias and power is to compare all CRC cases with
      all controls, ignoring polyps. 

PMID- 26306666
TI  - A composite of complex and chemical hydrides yields the first Al-based
      amidoborane with improved hydrogen storage properties.
AB  - The first Al-based amidoborane Na[Al(NH2 BH3 )4 ] was obtained through a
      mechanochemical treatment of the NaAlH4 -4 AB (AB=NH3 BH3 ) composite releasing
      4.5 wt % of pure hydrogen. The same amidoborane was also produced upon heating
      the composite at 70  degrees C. The crystal structure of Na[Al(NH2 BH3 )4 ],
      elucidated from synchrotron X-ray powder diffraction and confirmed by DFT
      calculations, contains the previously unknown tetrahedral ion [Al(NH2 BH3 )4 ](-)
      , with every NH2 BH3 (-) ligand coordinated to aluminum through nitrogen atoms.
      Combination of complex and chemical hydrides in the same compound was possible
      due to both the lower stability of the Al?H bonds compared to the B?H ones in
      borohydride, and due to the strong Lewis acidity of Al(3+) . According to the
      thermogravimetric analysis-differential scanning calorimetry-mass spectrometry
      (TGA-DSC-MS) studies, Na[Al(NH2 BH3 )4 ] releases in two steps 9 wt % of pure
      hydrogen. As a result of this decomposition, which was also supported by
      volumetric studies, the formation of NaBH4 and amorphous product(s) of the
      surmised composition AlN4 B3 H(0-3.6) were observed. Furthermore, volumetric
      experiments have also shown that the final residue can reversibly absorb about 27
      % of the released hydrogen at 250  degrees C and p(H2 )=150 bar. Hydrogen re
      absorption does not regenerate neither Na[Al(NH2 BH3 )4 ] nor starting materials,
      NaAlH4 and AB, but rather occurs within amorphous product(s). Detailed studies of
      the latter one(s) can open an avenue for a new family of reversible hydrogen
      storage materials. Finally, the NaAlH4 -4 AB composite might become a starting
      point towards a new series of aluminum-based tetraamidoboranes with improved
      hydrogen storage properties such as hydrogen storage density, hydrogen purity,
      and reversibility. 

PMID- 26306667
TI  - Development and pilot testing of Baby-Led Introduction to SolidS--a version of
      Baby-Led Weaning modified to address concerns about iron deficiency, growth
      faltering and choking.
AB  - BACKGROUND: In Baby-Led Weaning (BLW), infants are offered 'finger' foods from
      the start of the complementary feeding period instead of being spoon-fed.
      Healthcare professionals have expressed concerns about adequacy of iron and
      energy intake, and about choking, for infants following Baby-Led Weaning.
      METHODS: We developed a modified version of BLW, Baby-Led Introduction to SolidS
      (BLISS), to address these concerns. In a 12-week pilot study, families who had
      chosen to use a BLW approach were assigned to BLISS (n = 14) or BLW (n = 9).
      BLISS participants received 2 intervention visits, resources and on-call support.
      BLW participants received no intervention. Participants were interviewed weekly
      for 12 weeks and completed a three-day weighed record or three 24-h iron
      questionnaires. RESULTS: Compared to the BLW group, the BLISS group were more
      likely to introduce iron containing foods during the first week of complementary
      feeding, and to offer more serves per day of iron containing foods at 6 months
      (2.4 vs 0.8 serves/day; P = 0.001); and less likely to offer high-choking-risk
      foods (3.24 vs 0.17 serves/day; P = 0.027). CONCLUSIONS: This pilot study
      suggests BLISS may result in higher iron intakes and lower choking risk than
      unmodified BLW. However, the results need to be confirmed in a large randomised
      controlled trial.

PMID- 26306669
TI  - Intelligent healthcare informatics in big data era.

PMID- 26306668
TI  - Neuroprotective effect of Spirulina fusiform and amantadine in the 6-OHDA induced
      Parkinsonism in rats.
AB  - BACKGROUND: Multi-factorial etiology exists in pathophysiology of
      neurodegenerative diseases. The imbalance of anti-oxidant enzymes and dopamine
      level leads to Parkinsonism. The objective of this study was to assess the
      protective effect of Spirulina fusiform alone and in combination with amantadine
      against Parkinsonism effect in 6-hydroxydopamine (6-OHDA) induced rat model.
      METHODS: S. fusiform was administered in different groups (500 mg/kg, once daily
      and twice daily) and a combination of spirulina (500 mg/kg, once daily) with
      amantadine (20 mg/kg once daily) for 30 days before and 14 days after a single
      injection of 6-OHDA into the dorsal striatum. Post lesion produced rotational
      behavior which was measured at two week intervals (37th and 44th day). Locomotors
      activity was also done at 44th and muscle coordination at 48th day. Dorsal
      striatum was isolated from rat brain for evaluating the antioxidant assays and
      dopamine content at 49th day. RESULTS: Both the body rotations (ipsilateral and
      contralateral) were found to have a statistically significant (p<0.001) decrease
      by 34.26 and 52% after treatment with spirulina (Twice a day) in spirulina
      treated lesioned group. A higher percentage of improvement was shown in the
      reduction of ipsilateral (57.34%) and contralateral (78.3%) rotations in
      combination of spirulina with amantadine treated lesioned group rather than
      spirulina alone treated lesioned groups when compared with positive control
      lesioned group. Body movements and locomotor activity were improved statistically
      (p<0.0001) significant in both treated lesioned groups (Combination of spirulina
      with amantadine and spirulina twice daily). Similar results were also seen in
      anti-oxidant levels which later on reached to the normal value. The levels of
      dopamine content had a statistically significant (p<0.0001) increase by 78.3%
      only in case of spirulina with amantadine treated lesioned group. CONCLUSION:
      Spirulina is a potent nutraceutical supplement all over the world, so my
      preclinical study may contribute to give an additional adjuvant drug therapy in
      aging related disorders (Neurodegenerative as well as diabetes associated
      neurodegenerative disorders).

PMID- 26306670
TI  - Small intestine dysfunction in Parkinson's disease.
AB  - The aim of this study was to assess the small bowel transit time in patients with
      Parkinson's disease (PD). Ten patients with PD with no gastrointestinal
      complaints and ten healthy control subjects were investigated using single photon
      emission computed tomography fused with computed tomography after swallowing of a
      specially prepared capsule containing technetium 99m, which allowed visualization
      of the passage in the intestines. Preliminary results show that the small
      intestine passage in PD patients was prolonged compared to controls.

PMID- 26306671
TI  - Vitamin D status and insulin sensitivity are novel predictors of resting
      metabolic rate: a cross-sectional analysis in Australian adults.
AB  - PURPOSE: Resting metabolic rate (RMR) accounts for two-thirds of the total energy
      expenditure in sedentary individuals. After accounting for traditional factors,
      there still remains a considerable unexplained variance in RMR. There is a
      pandemic of obesity and metabolic syndrome (MetS) which coexists with a high
      prevalence of vitamin D insufficiency. The aim of this study was to evaluate the
      potential effects of vitamin D status, insulin sensitivity (IS) and the metabolic
      syndrome (MetS) on RMR in Australian adults. METHODS: RMR, respiratory quotient
      (RQ), McAuley's insulin sensitivity index, fat mass (FM), fat-free mass (FFM) and
      vitamin D status were assessed in Australian adults. The presence of MetS was
      evaluated by current standard criteria. Predictors of RMR were examined through
      multiple linear regression based on stepwise and backward regression approaches
      with attention to multi-collinearity. All analyses were conducted on SPSS version
      21. RESULTS: One hundred and twenty-seven participants (45 men, 82 women), aged
      53.4 +/- 11.7 years and BMI 31.9 +/- 5.2 kg/m(2), were included. Forty-one
      subjects were insufficient in vitamin D status (<50 nmol/L), and 75 participants
      had the MetS. A parsimonious regression model explained 85.8 % of RMR and was
      given by: RMR (kJ/d) = 1931 + 83.5 * FFM (kg) + 29.5 * FM (kg) + 5.65 * 25(OH)D
      (nmol/L) - 17.6 * age (years) - 57.51 * IS. CONCLUSION: Vitamin D status and IS
      are novel independent predictors of RMR in adults. Future studies could validate
      a causal role for these factors in human energy metabolism.

PMID- 26306673
TI  - Urinary iodine excretion and thyroid function status in school age children of
      hilly and plain regions of Eastern Nepal.
AB  - BACKGROUND: Iodine deficiency is a major public health problem in many developing
      countries including Nepal. The present study was designed to investigate the
      urinary iodine excretion (UIE), thyroid function status and household salt iodine
      content (SIC) in school-aged children (SAC) and to establish the relationships
      between these factors. METHODS: A community-based cross sectional study was
      conducted in selected schools of two districts, Tehrathum and Morang, lying in
      the hill and plain region of eastern Nepal respectively. A total of 640 SAC,
      (Tehrathum n = 274 and Morang n = 366) aged 6-11 years, were assessed for UIE and
      household SIC. Among the 640 children, 155 consented to blood samples (Tehrathum
      n = 78 and Morang n = 77) to test for serum thyroglobulin (Tg), thyroid
      stimulating hormone (TSH), free triiodothyronine (fT3) and free thyroxine (fT4).
      UIE was measured by ammonium persulfate digestion method. SIC was measured by
      iodometric titration method and Tg, TSH, fT4 and fT3 were measured by immunoassay
      based kit method. RESULTS: In Tehrathum and Morang, 9.5 and 7.7% of SAC had UIE
      values of UIE <100 ug/L while 59.5 and 41% had iodine nutrition values of >299
      ug/L, with median UIE of 345.65 and 270.36 ug/L respectively. The overall medians
      were as follows, Tg 14.29 ug/L, fT3 3.94 pmol/L, fT4 16.25 pmol/L and TSH 3.61
      mIU/L. There was a negative correlation between UIE and Tg (r = -0.236, p =
      0.003) and a positive correlation between UIE and SIC (r = 0.349, p < 0.0001). We
      found 19.5%, n = 15 and 16.7%, n = 13 subclinical hypothyroid cases in Morang and
      Tehrathum respectively. Iodometric titration showed only 6.4% (n = 41) of the
      samples had household SIC <15 ppm. Multivariate analysis revealed that use of
      packaged salt by SAC of Tehrathum district correlated with higher UIE values.
      CONCLUSIONS: Our focused data suggests that collaborative universal salt
      iodization (USI) programs are improving the health of children in the Tehrathum
      and Morang districts of Nepal. We also found that excessive iodine in a large
      portion of the study groups is a substantial concern and iodine intervention
      programs need to deal with both deficient and excessive iodine scenarios that can
      both be present simultaneously in study populations.

PMID- 26306672
TI  - The tumor suppressor HHEX inhibits axon growth when prematurely expressed in
      developing central nervous system neurons.
AB  - Neurons in the embryonic and peripheral nervous system respond to injury by
      activating transcriptional programs supportive of axon growth, ultimately
      resulting in functional recovery. In contrast, neurons in the adult central
      nervous system (CNS) possess a limited capacity to regenerate axons after injury,
      fundamentally constraining repair. Activating pro-regenerative gene expression in
      CNS neurons is a promising therapeutic approach, but progress is hampered by
      incomplete knowledge of the relevant transcription factors. An emerging
      hypothesis is that factors implicated in cellular growth and motility outside the
      nervous system may also control axon growth in neurons. We therefore tested sixty
      nine transcription factors, previously identified as possessing tumor suppressive
      or oncogenic properties in non-neuronal cells, in assays of neurite outgrowth.
      This screen identified YAP1 and E2F1 as enhancers of neurite outgrowth, and
      PITX1, RBM14, ZBTB16, and HHEX as inhibitors. Follow-up experiments are focused
      on the tumor suppressor HHEX, one of the strongest growth inhibitors. HHEX is
      widely expressed in adult CNS neurons, including corticospinal tract neurons
      after spinal injury, but is present only in trace amounts in immature cortical
      neurons and adult peripheral neurons. HHEX overexpression in early postnatal
      cortical neurons reduced both initial axonogenesis and the rate of axon
      elongation, and domain deletion analysis strongly implicated transcriptional
      repression as the underlying mechanism. These findings suggest a role for HHEX in
      restricting axon growth in the developing CNS, and substantiate the hypothesis
      that previously identified oncogenes and tumor suppressors can play conserved
      roles in axon extension. 

PMID- 26306674
TI  - Statin use in spontaneous intracerebral hemorrhage: a systematic review and meta
      analysis.
AB  - BACKGROUND: Nonrandomized observational studies have been conducted to evaluate
      the effects of statins on clinical outcomes in patients with intracerebral
      hemorrhage. Several studies on the effects of statin administration in patients
      with intracerebral hemorrhage have been published recently, but the findings are
      inconsistent. AIM: To evaluate the effects of statins administered prior to
      hospital admission and during hospitalization on mortality and functional
      outcomes in patients with intracerebral hemorrhage. SUMMARY OF REVIEW: We
      searched for relevant literature using multiple comprehensive databases and
      performed a systematic review and meta-analysis. Sixteen studies met our
      selection criteria. Preintracerebral hemorrhage statin use was not associated
      with mortality (odds ratio: 0.90, 95% confidence interval: 0.63-1.28). However,
      patients who used statins prior to intracerebral hemorrhage had a decreased risk
      of mortality at three-months following symptom onset (odds ratio: 0.47, 95%
      confidence interval: 0.32-0.68) and an increased probability of good functional
      outcomes (odds ratio: 1.49, 95% confidence interval: 1.01-2.19), as compared with
      those who did not. In-hospital use of statins was associated with a low risk of
      mortality (odds ratio: 0.34, 95% confidence interval: 0.26-0.44) irrespective of
      preadmission statin use or postadmission time-points. Additionally, we were
      unable to pool the data on statin withdrawal because of differences in study
      methodologies. CONCLUSIONS: Although careful interpretation is necessary due to
      several study limitations, we have demonstrated that statin use in patients with
      intracerebral hemorrhage is likely associated with improved mortality and
      functional outcomes.

PMID- 26306675
TI  - Blockade of autophagy enhances proapoptotic potential of BI-69A11, a novel Akt
      inhibitor, in colon carcinoma.
AB  - BI-69A11, novel Akt inhibitor, is currently drawing much attention due to its
      intriguing effect in inducing apoptosis in melanoma, breast, prostate and colon
      cancer. However, earlier reports reveal that PI3K/Akt/mTOR inhibitors promote
      autophagy at the early stage as a survival mechanism that might affect its
      apoptotic potential. It is necessary to investigate whether BI-69A11 mediated
      apoptosis is associated with autophagy for enhancing its therapeutic efficacy.
      Here, we found that BI-69A11 induced autophagy at earlier time point through the
      inhibition of Akt/mTOR/p70S6kinase pathway. Dose-dependent and time-dependent
      conversion of LC3-I to LC3-II, increased accumulation of LC3-GFP dots in
      cytoplasm and increase in other autophagic markers such as Beclin-1, firmly
      supported the fact that BI-69A11 induces autophagy. Atg5, Atg7 and Beclin-1 siRNA
      mediated genetic attenuation and pre-treatment with pharmacological inhibitor 3
      MA and CQ diminished the autophagy and increased the propensity of cell death
      towards apoptosis. It was also suggested that BI-69A11 mediated interaction
      between Akt, HSP-90 and Beclin-1 maintained the fine balance between autophagy
      and apoptosis. Interaction between Beclin-1 and HSP90 is one of the prime causes
      of induction of autophagy. Here, we also generated a novel combination therapy by
      pretreatment with CQ that inhibited the autophagy and accelerated the apoptotic
      potential of BI-69A11. In summary; our findings suggest that induction of
      autophagy lead to the resistance of colon cancer towards BI-69A11 mediated
      apoptosis.

PMID- 26306676
TI  - Preferential adsorption of cell adhesive proteins from complex media on self
      assembled monolayers and its effect on subsequent cell adhesion.
AB  - We examined the effect of surface chemistry on adsorption of fibronectin (Fn) and
      vitronectin (Vn) and subsequent cell adhesion, employing self-assembled
      monolayers (SAMs) of alkanethiols carrying terminal methyl (CH3), hydroxyl groups
      (OH), carboxylic acid (COOH), and amine (NH2). More Fn and Vn adsorbed to COOH-
      and NH2-SAMs than to CH3- and OH-SAMs from a mixture with bovine serum albumin
      (BSA) and from 2% fetal bovine serum. Adhesion of human umbilical vein
      endothelial cells (HUVECs) on CH3- and OH-SAMs preadsorbed with Fn and BSA
      decreased with decreasing adsorbed Fn; however, HUVECs adhered to COOH- and NH2
      SAMs even in the presence of BSA at 1000-fold more than Fn in a mixture because
      of the preferential adsorption of Fn and/or displacement of preadsorbed BSA with
      Fn and Vn in a serum-containing medium. SAMs coated with a mixture of Vn and BSA
      exhibited adhesion of HUVECs regardless of surface functional groups. A well
      organized focal adhesion complex and actin stress fibers were observed only for
      COOH- and NH2-SAMs when SAMs were preadsorbed with Vn and BSA. These results
      suggest that COOH- and NH2-SAMs allow for both cell adhesion and cell spreading
      because of the high density of cell-binding domains derived from adsorbed Vn.
      STATEMENT OF SIGNIFICANCE: Adsorption of cell adhesive proteins including
      fibronectin (Fn) and vitronectin (Vn) plays an important role in cell adhesion to
      artificial materials. However, for the development of biomaterials that contact
      with biological fluids, it is important to understand adsorption of Fn and Vn in
      complex media containing many kinds of proteins. Here, we focused on adsorption
      of Fn and Vn from complex media including mixed solution with albumin and fetal
      bovine serum, and its role on cell adhesion using self-assembled monolayers
      (SAMs). Our result demonstrates that SAMs carrying carboxylic acid or amine allow
      for both cell adhesion and cell spreading because of preferentially adsorbed Vn.
      The result provides insights into surface design of cell culture substrates and
      tissue engineering scaffolds.

PMID- 26306677
TI  - Prospective phase II study of tomotherapy based chemoradiation treatment for
      locally advanced anal cancer.
AB  - BACKGROUND AND PURPOSE: To evaluate toxicity, local control, and survival of anal
      cancer patients treated with helical tomotherapy (HT) and concurrent 5
      fluorouracil and mitomycin-C (5FU/MMC). MATERIALS AND METHODS: Fifty-seven
      patients were treated with HT and concurrent 5FU/MMC. The planning objectives
      were to deliver 54 Gy to the tumor (PTV54) and 45 Gy to the nodes at risk (PTV45)
      in 30 fractions. Patients were reviewed for toxicity weekly during HT, every 6
      weeks for 3 months, and then every 3-4 months for 5 years. RESULTS: The median
      follow-up was 40 months. The median age was 58 years (range: 37-83). Stage
      distribution: stage II-48%, IIIA-18%, IIIB-34%. The majority of patients
      developed ? grade 2 acute toxicity scores. The most common ? grade 3 acute
      toxicity was neutropenia (40%). Common late toxicities were grade 2 anal
      incontinence (16%) and telangiectasia (12%). The 3 year colostomy-free survival
      rate was 77% (95% CI: 61-87%), 3 year disease-free survival rate was 80% (CI: 66
      89%), and 3 year overall survival was 91% (CI: 77-96%). CONCLUSIONS:
      Incorporation of HT with concurrent 5FU/MMC had low treatment-related acute and
      late morbidity with few treatment breaks. However, the expected dosimetric
      benefit for hematological toxicity was not experienced clinically.

PMID- 26306678
TI  - Accurate prediction of target dose-escalation and organ-at-risk dose levels for
      non-small cell lung cancer patients.
AB  - PURPOSE/OBJECTIVE: To develop a method to predict feasible organ-at-risk (OAR)
      and tumour dose levels of non-small cell lung cancer (NSCLC) patients prior to
      the start of treatment planning. MATERIALS/METHODS: Included were NSCLC patients
      treated with volumetric modulated arc therapy according to an institutional
      isotoxic dose-escalation protocol. A training cohort (N=50) was used to calculate
      the average dose inside the OARs as a function of the distance to the planning
      target volume (PTV). These dose-distance relations were used in a validation
      cohort (N=39) to predict dose-volume histograms (DVHs) of OARs and PTV as well as
      the maximum individualized PTV dose escalation. RESULTS: The validation cohort
      showed that predicted and achieved MLD were in agreement with each other
      (difference: -0.1+/-1.9 Gy, p=0.81). The spinal cord was dose limiting in only
      two patients, which was correctly predicted. The achieved mean PTV dose varied
      from 52 to 73 Gy and was predicted correctly with an accuracy better than 2 Gy
      (i.e. 1 fraction) for 79% of the patients. CONCLUSION: We have shown that the MLD
      and the prescribed PTV dose could be accurately predicted for NSCLC patients.
      This method can guide the treatment planner to achieve optimal OAR sparing and
      tumour dose escalation.

PMID- 26306679
TI  - Two methods for proteomic analysis of formalin-fixed, paraffin embedded tissue
      result in differential protein identification, data quality, and cost.
AB  - Formalin-fixed paraffin-embedded (FFPE) tissue is a rich source of clinically
      relevant material that can yield important translational biomarker discovery
      using proteomic analysis. Protocols for analyzing FFPE tissue by LC-MS/MS exist,
      but standardization of procedures and critical analysis of data quality is
      limited. This study compared and characterized data obtained from FFPE tissue
      using two methods: a urea in-solution digestion method (UISD) versus a
      commercially available Qproteome FFPE Tissue Kit method (Qkit). Each method was
      performed independently three times on serial sections of homogenous FFPE tissue
      to minimize pre-analytical variations and analyzed with three technical
      replicates by LC-MS/MS. Data were evaluated for reproducibility and
      physiochemical distribution, which highlighted differences in the ability of each
      method to identify proteins of different molecular weights and isoelectric
      points. Each method replicate resulted in a significant number of new protein
      identifications, and both methods identified significantly more proteins using
      three technical replicates as compared to only two. UISD was cheaper, required
      less time, and introduced significant protein modifications as compared to the
      Qkit method, which provided more precise and higher protein yields. These data
      highlight significant variability among method replicates and type of method
      used, despite minimizing pre-analytical variability. Utilization of only one
      method or too few replicates (both method and technical) may limit the subset of
      proteomic information obtained. 

PMID- 26306680
TI  - Efficacy of Noncontrast Computed Tomography of the Abdomen and Pelvis for
      Evaluating Nontraumatic Acute Abdominal Pain in the Emergency Department.
AB  - BACKGROUND: Computed tomography (CT) clarity has significantly improved since it
      became widely available in the early 1980s, making the utility and benefit of
      contrast material for image quality of the abdomen and pelvis uncertain, and so
      far, minimally studied. OBJECTIVES: This study sought to assess the efficacy of a
      noncontrast CT scan of the abdomen and pelvis by evaluating patients presenting
      to the emergency department (ED) with acute nontraumatic abdominal pain by
      following them for 7 days and observing for signs and symptoms of clinically
      significant acute emergent pathology. METHODS: We enrolled, and for 7 days
      followed, a prospective observational convenience sample of patients who received
      a noncontrast CT scan of the abdomen and pelvis in the ED for acute nontraumatic
      abdominal pain. The primary outcome, and defined as a failure, was abdominal
      surgery or death as the result of an intraabdominal process not found on the
      original noncontrast CT scan, or a subsequent contrasted CT scan with a finding
      that could explain the original complaint of abdominal pain that was also not
      seen on the initial noncontrast CT, during the 7-day observation. RESULTS:
      Seventy-two patients were enrolled in the study. The incidence of failure was 0%
      (0/72), 46% of patients (33/72) had a negative CT scan, 54% (39/72) had a
      positive CT scan, 57% (41/72) were admitted, 43% (31/72) discharged, 11% (8/72)
      had abdominal surgery, and a repeat contrasted CT scan was done on 4% (3/72).
      CONCLUSIONS: With certain inclusion and exclusion criteria, noncontrast CT of the
      abdomen and pelvis is likely a reliable diagnostic modality for the evaluation of
      acute nontraumatic abdominal pain in the ED.

PMID- 26306681
TI  - Life in the Slow Lane: "Life, Trauma, Death: A Resident Physician's Perspective":
      A Response.

PMID- 26306683
TI  - Filling a lacune in perinatal stroke outcomes.

PMID- 26306682
TI  - Chamber identity programs drive early functional partitioning of the heart.
AB  - The vertebrate heart muscle (myocardium) develops from the first heart field
      (FHF) and expands by adding second heart field (SHF) cells. While both lineages
      exist already in teleosts, the primordial contributions of FHF and SHF to heart
      structure and function remain incompletely understood. Here we delineate the
      functional contribution of the FHF and SHF to the zebrafish heart using the cis
      regulatory elements of the draculin (drl) gene. The drl reporters initially
      delineate the lateral plate mesoderm, including heart progenitors. Subsequent
      myocardial drl reporter expression restricts to FHF descendants. We harnessed
      this unique feature to uncover that loss of tbx5a and pitx2 affect relative FHF
      versus SHF contributions to the heart. High-resolution physiology reveals
      distinctive electrical properties of each heart field territory that define a
      functional boundary within the single zebrafish ventricle. Our data establish
      that the transcriptional program driving cardiac septation regulates physiologic
      ventricle partitioning, which successively provides mechanical advantages of
      sequential contraction. 

PMID- 26306684
TI  - The Life Course Perspective: a Guide for Genetic Counselors.
AB  - This is the first article in a two part series about utilizing the life course
      perspective (LCP) in genetic counseling. LCP can be a useful tool for genetic
      counselors when counseling people with a known genetic mutation. Previous
      theories such as Protection Motivation Theory (PMT) and Common Sense Model of
      Self-Regulation (CSMSR) examine current reactions to a positive genetic test
      result. LCP extends beyond the current time to explore temporal and contextual
      elements of the experience. A review of research revealed, LCP has been used to
      study the perspective of caregivers of people with Alzheimer's disease, referral
      for a family history of breast cancer, Mexican American caregivers of older
      adult, social class and cancer incidence and cancer and the sense of mastery.
      Incorporating LCP into a study explaining the experiences of people living with a
      positive test result for a genetic mutation such as the BRCA mutation provides a
      comprehensive exploration of this experience. 

PMID- 26306686
TI  - Large-area, free-standing, two-dimensional supramolecular polymer single-layer
      sheets for highly efficient electrocatalytic hydrogen evolution.
AB  - The rational construction of covalent or noncovalent organic two-dimensional
      nanosheets is a fascinating target because of their promising applications in
      electronics, membrane technology, catalysis, sensing, and energy technologies.
      Herein, a large-area (square millimeters) and free-standing 2D supramolecular
      polymer (2DSP) single-layer sheet (0.7-0.9 nm in thickness), comprising
      triphenylene-fused nickel bis(dithiolene) complexes has been readily prepared by
      using the Langmuir-Blodgett method. Such 2DSPs exhibit excellent electrocatalytic
      activities for hydrogen generation from water with a Tafel slope of 80.5 mV
      decade(-1) and an overpotential of 333 mV at 10 mA cm(-2) , which are superior to
      that of recently reported carbon nanotube supported molecular catalysts and
      heteroatom-doped graphene catalysts. This work is promising for the development
      of novel free-standing organic 2D materials for energy technologies. 

PMID- 26306685
TI  - Genetic Knowledge Among Participants in the Coriell Personalized Medicine
      Collaborative.
AB  - Genetic literacy is essential for the effective integration of genomic
      information into healthcare; yet few recent studies have been conducted to assess
      the current state of this knowledge base. Participants in the Coriell
      Personalized Medicine Collaborative (CPMC), a prospective study assessing the
      impact of personalized genetic risk reports for complex diseases and drug
      response on behavior and health outcomes, completed genetic knowledge
      questionnaires and other surveys through an online portal. To assess the
      association between genetic knowledge and genetic education background,
      multivariate linear regression was performed. 4 062 participants completed a
      genetic knowledge and genetic education background questionnaire. Most were older
      (mean age: 50), Caucasian (90 %), female (59 %), highly educated (69 % bachelor's
      or higher), with annual household income over $100 000 (49 %). Mean percent
      correct was 76 %. Controlling for demographics revealed that health care
      providers, participants previously exposed to genetics, and participants with
      'better than most' self-rated knowledge were significantly more likely to have a
      higher knowledge score (p < 0.001). Overall, genetic knowledge was high with
      previous genetic education experience predictive of higher genetic knowledge
      score. Education is likely to improve genetic literacy, an important component to
      expanded use of genomics in personalized medicine.

PMID- 26306687
TI  - Myeloradiculopathy associated with chikungunya virus infection.
AB  - Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that is endemic to parts
      of Africa, South and Southeast Asia, and more recently the Caribbean. Patients
      typically present with fever, rash, and arthralgias, though neurologic symptoms,
      primarily encephalitis, have been described. We report the case of a 47-year-old
      woman who was clinically diagnosed with CHIKV while traveling in the Dominican
      Republic and presented 10 days later with left lower extremity weakness, a
      corresponding enhancing thoracic spinal cord lesion, and positive CHIKV
      serologies. She initially responded to corticosteroids, followed by relapsing
      symptoms and gradual clinical improvement. The time lapse between acute CHIKV
      infection and the onset of myelopathic sequelae suggests an immune-mediated
      phenomenon rather than direct activity of the virus itself. Chikungunya virus
      should be considered in the differential diagnosis of myelopathy in endemic
      areas. The progression of symptoms despite corticosteroid administration suggests
      more aggressive immunomodulatory therapies may be warranted at disease onset. 

PMID- 26306688
TI  - Human immunodeficiency virus has similar effects on brain volumetrics and
      cognition in males and females.
AB  - Most studies that have examined neuropsychological impairments associated with
      human immunodeficiency virus (HIV) have focused on males, yet females represent
      one of the largest groups of newly infected patients. Further, few studies have
      examined neuropsychological performance and neuroimaging outcomes among females
      compared to males in the modern era of highly active anti-retroviral therapy
      (HAART). The present study investigated neuropsychological performance and brain
      volumetrics among HIV+ males (n = 93) and females (n = 44) on stable HAART
      compared to HIV seronegative (HIV-) males (n = 42) and females (n = 49). Results
      revealed a significant effect of HIV on neuropsychological performance and
      neuroimaging measures. An effect of gender, independent of HIV status, was also
      observed for neuroimaging measures but not neuropsychological performance.
      Additionally, no significant differences in neuropsychological performance or
      brain volumetrics were seen between HIV+ males and females. No significant
      interaction was observed between HIV and gender on either neuropsychological or
      neuroimaging indices. Our results suggest that both HIV+ males and females
      treated with HAART experience similar outcomes in terms of brain integrity. 

PMID- 26306689
TI  - Nicotine mediates expression of genes related to antioxidant capacity and
      oxidative stress response in HIV-1 transgenic rat brain.
AB  - Oxidative stress plays an important role in the progression of HIV-1 infection.
      Nicotine can either protect neurons from neurodegeneration or induce oxidative
      stress, depending on its dose and degree of oxidative stress impairment. However,
      the relationship between nicotine and oxidative stress in the HIV-1-infected
      individuals remains largely unknown. The purpose of this study was to determine
      the effect of nicotine on expression of genes related to the glutathione (GSH)
      centered antioxidant system and oxidative stress in the nucleus accumbens (NAc)
      and ventral tegmental area (VTA) of HIV-1 transgenic (HIV-1Tg) and F344 control
      rats. Adult HIV-1Tg and F344 rats received nicotine (0.4 mg/kg, base, s.c.) or
      saline injections once per day for 27 days. At the end of treatment, various
      brain regions including the NAc and VTA were collected from each rat. Following
      total RNA extraction and complementary DNA (cDNA) synthesis of each sample,
      quantitative reverse transcription PCR (RT-PCR) analysis was performed for 43
      oxidative-stress-related genes. Compared with F344 control rats, HIV-1Tg rats
      showed a significant downregulation of genes involved in ATPase and cyctochrome
      oxidase at the messenger RNA (mRNA) level in both regions. Further, we found a
      significant downregulation of Gstm5 in the NAc and upregulation of Cox1, Cox3,
      and Gsta6 in the VTA of HIV-1Tg rats. HIV-1Tg rats showed brain-region-specific
      responses to chronic nicotine treatment. This response resulted in a change in
      the expression of genes involved in antioxidant mechanisms including the
      downregulation of genes such as Atp5h, Calml1, Gpx7, Gstm5, Gsr, and Gsta6 and
      upregulation of Sod1 in the NAc, as well as downregulation of genes like Cox5a,
      Gpx4, Gpx6, Gpx7, Gstm5, and Sod1 in the VTA of HIV-1Tg rats. Together, we
      conclude that chronic nicotine treatment has a dual effect on the antioxidant
      defense system and oxidative-stress-induced apoptosis signaling in HIV-1Tg rats.
      These findings suggest that nicotine has a negative effect on response to
      oxidative stress and antioxidant processes in HIV-1 Tg rat brain, especially in
      the VTA. 

PMID- 26306690
TI  - Subtype associations with HIV-associated neurocognitive disorder in China.
AB  - Factors associated with HIV-associated neurocognitive disorders (HAND) include
      CD4(+) nadir and count, HIV RNA level, and HIV-1 subtype. Here, we investigated
      demographical and clinical markers with respect to HAND in a homogenous Chinese
      population. Individuals with HAND (global deficit score >=0.5) had lower nadir (p
      < 0.01) and CD4(+) counts (p = 0.03). HAND was also associated with AIDS (p <
      0.01), but subtype was not (p = 0.198). Furthermore, worse impairment correlated
      with higher viral diversity (r = 0.16, p < 0.01), lower nadir (r = -0.17, p <
      0.01), and CD4(+) counts (r = -0.11, p = 0.01). These remained significant even
      when correcting for subtype. Our findings suggest that subtype does not have a
      major impact on HAND.

PMID- 26306691
TI  - Effect of a patient-centered drug review on polypharmacy in primary care
      patients: study protocol for a cluster-randomized controlled trial.
AB  - BACKGROUND: Managing patients with polypharmacy is a challenging issue in primary
      care. The aim of this study is to determine whether a patient-centered systematic
      review leads to more appropriate medication use in patients without negatively
      affecting quality of life and the course of the disease. METHODS/DESIGN: The
      trial is a two-armed, double blinded cluster-randomized controlled trial. Primary
      care physicians (PCPs) will be randomly assigned to the intervention or control
      group. Physicians in the intervention group undergo training with instruction of
      the algorithm. The control group is given a lecture on multimorbidity and
      instructions for collecting data in a usual care manner. PCPs will approach
      patients aged 60 years or older who are taking 5 or more drugs. The study period
      is 1 year. The primary outcome measure is the change in the number of drugs 12
      months after the algorithm was applied by the PCP during consultation with the
      patient. Secondary outcomes are: change in the number of drugs immediately after
      the encounter and 6 months later, reason for a change of the medication,
      discrepancy in the decision to change between PCP and patient, number of drugs
      for which the patient is suggesting a change, number of drugs the patient is
      taking that are not known to the PCP, time consumption of the intervention,
      disease-specific variables to evaluate the course of the disease(s) for which the
      patient is being treated , quality of life, barriers against using the algorithm,
      numbers of drugs readopted due to an unfavorable course of the disease, and
      numbers of drugs which have been started. DISCUSSION: Answering the four
      questions of the algorithm requires a weighing-up of risks and benefits and
      contains a shared-decision-making approach: a prioritization of the treatment
      goals is necessary. This can only be done in collaboration with the patient. The
      majority of patients with multimorbidity are treated in the primary care setting.
      This underlines the significance of our study carried out in this setting: given
      the high prevalence of adverse drug events in patients with multimorbidity an
      intervention like ours has a large potential to reduce drug-related morbidity.
      TRIAL REGISTRATION: ISRCTN16560559 13 November 2014.

PMID- 26306692
TI  - Absorption and Phase Contrast X-Ray Imaging in Paleontology Using Laboratory and
      Synchrotron Sources.
AB  - X-ray micro-computed tomography (MUCT) is commonly used for imaging of samples in
      biomedical or materials science research. Owing to the ability to visualize a
      sample in a nondestructive way, X-ray MUCT is perfectly suited to inspect
      fossilized specimens, which are mostly unique or rare. In certain regions of the
      world where important sedimentation events occurred in the Precambrian geological
      time, several fossilized animals are studied to understand questions related to
      their origin, environment, and life evolution. This article demonstrates the
      advantages of applying absorption and phase-contrast CT on the enigmatic fossil
      Corumbella werneri, one of the oldest known animals capable of building hard
      parts, originally discovered in Corumba (Brazil). Different tomographic setups
      were tested to visualize the fossilized inner structures: a commercial laboratory
      based MUCT device, two synchrotron-based imaging setups using conventional
      absorption and propagation-based phase contrast, and a commercial X-ray
      microscope with a lens-coupled detector system, dedicated for radiography and
      tomography. Based on our results we discuss the strengths and weaknesses of the
      different imaging setups for paleontological studies. 

PMID- 26306693
TI  - Automated quantification of left atrial size using three-beat averaging real-time
      three dimensional Echocardiography in patients with atrial fibrillation.
AB  - BACKGROUND: Left atrial (LA) sizing in patients with atrial fibrillation (AF) is
      crucial for follow-up and outcome. Recently, the automated quantification of LA
      using the novel three-beat averaging real-time three dimensional echocardiography
      (3BA-RT3DE) is introduced. The aim of this study was to assess the feasibility
      and accuracy of 3BA-RT3DE in patients with atrial fibrillation (AF). METHODS:
      Thirty-one patients with AF (62.8 +/- 11.7 years, 67.7 % male) were prospectively
      recruited to have two dimensional echocardiography (2DE) and 3BA-RT3DE (SC 2000,
      ACUSON, USA). The maximal left atrial (LA) volume was measured by the
      conventional prolate-ellipse (PE) and area-length (AL) method using three-beat
      averaging 2D transthoracic echocardiography and automated software analysis (eSie
      volume analysis, Siemens Medical Solution, Mountain view, USA); measurements were
      compared with those obtained by computed tomography (CT). RESULTS: Maximal LA
      volume by 3BA-RT3DE was feasible for all patients. LA volume was 68.4 +/- 28.2 by
      PE-2DE, 89.2 +/- 33.1 by AL-2DE, 100.6 +/- 31.8 by 3BA-RT3DE, and 131.2 +/- 42.2
      mL by CT. LA volume from PE-2DE (R(2) = 0.48, p < 0.001, ICC = 0.64, p < 0.001),
      AL-2DE (R(2) = 0.47, p < 0.001, ICC = 0.67, p < 0.001), and 3BA-RT3DE (R(2) =
      0.50, p = 0.001, ICC = 0.65, p < 0.001) showed significant correlations with CT.
      However, 3BA-RT3DE demonstrated a small degree of underestimation (30.5 mL) of LA
      volume compared to 2DE-based measurements. Good-quality images from 3BA-RT3DE (n
      = 16) showed a significantly tighter correlation with images from CT scanning
      (R(2) = 0.60, p = 0.0004, ICC = 0.76, p < 0.001) compared to those of fair
      quality. CONCLUSION: Automated quantification of LA volume using 3BA-RT3DE is
      feasible and accurate in patients with AF. An image of good quality is essential
      for maximizing the value of this method in clinical practice.

PMID- 26306694
TI  - Clinical characteristics of catamenial and non-catamenial thoracic endometriosis
      related pneumothorax.
AB  - BACKGROUND AND OBJECTIVE: A major pathogenic factor for catamenial pneumothorax
      is thoracic endometriosis. However, thoracic endometriosis-related pneumothorax
      (TERP) can develop as either catamenial or non-catamenial pneumothorax (CP).
      Therefore, the aim of this study was to elucidate the clinical differences
      between catamenial and non-catamenial TERP. METHODS: The clinical and
      pathological data in female patients who underwent video-assisted thoracoscopic
      surgery at the Pneumothorax Research Center during an 8-year period were
      retrospectively reviewed. This study included 150 female patients with surgico
      pathologically confirmed TERP. The subjects were divided into two groups, those
      having all of the pneumothorax episodes in the catamenial period (CP group) and
      those who did not (non-CP group). We compared the clinical characteristics and
      surgico-pathological findings between these two groups. RESULTS: Of the 150 TERP
      patients, 55 (36.7%) were classified in the CP group, and 95 (63.3%) in the non
      CP group. In regard to the locations of endometriosis, all TERP patients had
      diaphragmatic endometriosis, while pleural implantation was recognized in 34 of
      the 55 (61.8%) patients in the CP group and 42 of the 95 (44.2%) patients in the
      non-CP group (P < 0.05). CONCLUSIONS: A significant difference in the proportion
      of patients with pleural endometriosis was observed between catamenial and non
      catamenial TERP. The ectopic sites of the endometriosis may be responsible for
      the timing of the pneumothorax episodes.

PMID- 26306695
TI  - The ventrolateral preoptic nucleus is required for propofol-induced inhibition of
      locus coeruleus neuronal activity.
AB  - The mechanisms underlying the unconsciousness of general anesthesia are not
      completely understood. Accumulating evidence indicates the ventrolateral preoptic
      nucleus (VLPO) in the endogenous sleep circuits may contribute to loss of
      consciousness (LOC) induced by GABA-enhancing anesthetics. However, there are few
      studies that look into distinct sleep pathway in the sleep-wake system. In the
      neural pathway from VLPO to the locus coeruleus (LC), we compared the inhibition
      effect of propofol on the LC activity before and after VLPO lesion in vivo rats.
      Systemic administration of propofol (20 mg/kg, i.p.) in normal rats caused a fast
      and obvious inhibition of LC neurons spontaneous firing (from 0.24 +/- 0.06 to
      0.12 +/- 0.03 Hz). The LC neuronal firing rate of VLPO lesion rats only decreased
      to 0.18 +/- 0.05 Hz (P = 0.021 vs. non-VLPO rats) after the propofol injection,
      and the time to reach the maximal inhibition level was also prolonged in VLPO
      lesion rats (2.3 +/- 0.7 vs. 5.8 +/- 1.2 min, P = 0.037). Microinjections of a
      selective GABAA receptor antagonist (SR95531) into the LC fully reversed the
      inhibitory effect of propofol on the LC neuronal activity, but did not
      significantly affect the latency to loss of righting reflex of rats after
      propofol administration (3.4 +/- 0.9 vs. 3.7 +/- 1.2 min, P = 0.639). Our results
      indicated that VLPO is necessary for the propofol-induced inhibition of LC
      activity, but the LC may not play an important role in the propofol-induced LOC.

PMID- 26306696
TI  - Late-onset primary dystonia in Zhejiang province of China: a service-based
      epidemiological study.
AB  - Dystonia is characterized by sustained muscle contractions, causing repetitive
      movements and abnormal postures. The epidemiological study of dystonia of Chinese
      population was limited reported. In this study, we investigated the epidemiology
      of primary dystonia, and its clinical characteristics in an adult population in
      China. We identified all dystonia patients from the movement disorders database
      and botulinum toxin clinic between 2009 and 2013. The medical records were
      reviewed to verify the diagnosis of dystonia, and demographic and clinical data
      were collected. A total of 1481 patients with primary dystonia were studied. The
      most common focal dystonia were blepharospasm (56.4 %), cervical dystonia (36.7
      %), limb dystonia (3.4 %), oromandibular dystonia (2.9 %) and laryngeal dystonia
      (0.6 %). Males with primary dystonia were found to have an earlier age of onset.
      A female predominance was noted for most of the primary dystonia, with a men to
      women ratio (M:F) of 1:2.01. The minimum estimate of prevalence of primary
      dystonia was 27.0 (95 % confidence interval: 25.6-28.3) per million persons in
      this study. Despite the difference in genetic background and geographic area, the
      epidemiological features of dystonia in China from our study share most features
      around the world, such as women dystonia dominance, early-onset age of dystonia
      with women, etc. But East Asia countries (China and Japan) may share more common
      features of dystonia.

PMID- 26306697
TI  - Effect of educational television commercial on pre-hospital delay in patients
      with ischemic stroke.
AB  - Administering intravenous recombinant tissue plasminogen activator (r-tPA) within
      4.5 h or endovascular procedures within 8 h of ischemic stroke onset may reduce
      the risk of disability. The effectiveness of media campaigns to raise stroke
      awareness and shorten pre-hospital delay is unclear. We studied 1144 consecutive
      ischemic stroke patients at Aomori Prefectural Central Hospital, Japan, between
      March 2010 and February 2014. From March 2012, the government sponsored an
      educational campaign based on a television commercial to improve knowledge of
      stroke symptoms and encourage ambulance calls for facial palsy, arm palsy, or
      speech disturbance. For the 544 and 600 patients admitted before and during the
      intervention, respectively, we recorded the National Institutes of Health Stroke
      Scale score, stroke type, the time when patients or bystanders recognized stroke
      symptoms, and hospital arrival time. Pre-hospital delay, as the time interval
      from awareness of stroke to hospital arrival, was categorized as 0-3, 3-6, and 6+
      h. The mean pre-hospital delay was shorter (12.0 vs 13.5 h; P = 0.0067), the
      proportion of patients arriving within 3 h was larger (55.7 vs 46.5 %; P =
      0.0021), and the proportion arriving after 6 h was smaller (32.7 vs 39.5 %; P =
      0.0162) in the intervention group than in the pre-intervention group. There was
      no significant difference in the proportion of patients treated with r-tPA (6 and
      7.5 % of the intervention and pre-intervention groups, respectively). A
      television-based public education campaign potentially reduced pre-hospital delay
      for ischemic stroke patients, but the r-tPA treatment rate was unchanged.

PMID- 26306698
TI  - Reply from Authors re: Adri C. Voogd, Rob H.A. Verhoeven. Treatment of the
      Primary Tumour in the Presence of Metastases: Lessons from Breast Cancer. Eur
      Urol 2016;69:797-9Reply from Authors re: Alfred I. Neugut, Edward P. Gelmann.
      Treatment of the Prostate in the Presence of Metastases: Lessons from Other Solid
      Tumors. Eur Urol 2016;69:795-6: The Time Is Ripe to Test the Hypothesis that
      Radical Prostatectomy Improves Survival in Men with Distant Metastatic Prostate
      Cancer.

PMID- 26306699
TI  - MEXPRESS: visualizing expression, DNA methylation and clinical TCGA data.
AB  - BACKGROUND: In recent years, increasing amounts of genomic and clinical cancer
      data have become publically available through large-scale collaborative projects
      such as The Cancer Genome Atlas (TCGA). However, as long as these datasets are
      difficult to access and interpret, they are essentially useless for a major part
      of the research community and their scientific potential will not be fully
      realized. To address these issues we developed MEXPRESS, a straightforward and
      easy-to-use web tool for the integration and visualization of the expression, DNA
      methylation and clinical TCGA data on a single-gene level ( http://mexpress.be ).
      RESULTS: In comparison to existing tools, MEXPRESS allows researchers to quickly
      visualize and interpret the different TCGA datasets and their relationships for a
      single gene, as demonstrated for GSTP1 in prostate adenocarcinoma. We also used
      MEXPRESS to reveal the differences in the DNA methylation status of the PAM50
      marker gene MLPH between the breast cancer subtypes and how these differences
      were linked to the expression of MPLH. CONCLUSIONS: We have created a user
      friendly tool for the visualization and interpretation of TCGA data, offering
      clinical researchers a simple way to evaluate the TCGA data for their genes or
      candidate biomarkers of interest.

PMID- 26306700
TI  - Average Weight of Seminal Vesicles: An Adjustment Factor for Radical
      Prostatectomy Specimens Weighed With Seminal Vesicles.
AB  - The International Society of Urological Pathology in 2010 recommended weighing
      prostates without seminal vesicles (SV) to include only prostate weight in
      prostate-specific antigen (PSA) density (PSAD) calculation, because SV do not
      produce PSA. Large retrospective cohorts exist with combined weight recorded that
      needs to be modified for retrospective analysis. Weights of prostates and SV were
      separately recorded in 172 consecutive prostatectomies. The average weight of SV
      and proportion of prostate weight from combined weight were calculated. The
      adjustment factors were then validated on databases of 2 other institutions. The
      average weight of bilateral SV was 6.4 g (range = 1-17.3 g). The prostate
      constituted on average 87% (range = 66% to 98%) of the total specimen weight.
      There was no correlation between patient age and prostate weight with SV weight.
      The best performing correction method was to subtract 6.4 g from total radical
      prostatectomy weight and to use this weight for PSAD calculation. The average
      weights of retrospective specimens weighed with SV were not significantly
      different between the 3 institutions. Using our data allowed calibration of the
      weights and PSAD between the cohorts weighed with and without SV. Thus, prostate
      weight in specimens including SV weight can be adjusted by subtracting 6.4 g,
      resulting in significant change of PSAD. Some institution-specific variations may
      exist, which could further increase the precision of retrospective analysis
      involving prostate weight and PSAD. However, unless institution-specific
      adjustment parameters are developed, we recommend that this correction factor be
      used for retrospective cohorts or in institutions where combined weight is still
      recorded. 

PMID- 26306701
TI  - Subcutaneous Implantable Cardioverter Defibrillator Lead Failure due to Twiddler
      Syndrome.
AB  - We present a case of Twiddler syndrome in a patient with a subcutaneous
      implantable cardioverter defibrillator (S-ICD). The patient presented herself to
      the outpatient clinic with pain in the left chest. Chest x-ray confirmed Twiddler
      syndrome and ICD read-out revealed lead failure resulting in absent heart rhythm
      sensing in one vector. The lead and pulse generator were extracted and a new S
      ICD system was reimplanted submuscular underneath the serratus anterior muscle to
      prevent reoccurrence. Lead investigation revealed an insulation defect caused by
      excessive mechanical stress. 

PMID- 26306702
TI  - Investigating carbohydrate isomers by IMS-CID-IMS-MS: precursor and fragment ion
      cross-sections.
AB  - Ion mobility spectrometry techniques (IMS and IMS-IMS) combined with collision
      induced dissociation (CID) and mass spectrometry (MS) are used to investigate the
      structures of singly-lithiated carbohydrate isomers. With the exception of some
      favorable cases, IMS-MS analyses of underivatized carbohydrates reveal that most
      isobaric precursor ions have similar collision cross sections (ccs). In contrast,
      ccs values for isomeric fragment ions obtained by IMS-CID-IMS-MS analysis are
      often different, and thus appear to be useful as a means of distinguishing the
      isomeric precursors. We report values of ccs (in He) for precursor- and
      associated-fragment ions for three monosaccharide isomers (glucose, galactose and
      fructose), ten disaccharide isomers (sucrose, leucrose, palatinose, trehalose,
      cellobiose, beta-gentiobiose, isomaltose, maltose, lactose and melibiose), and
      three trisaccharide isomers (raffinose, melezitose and maltotriose). These values
      are discussed as a means of differentiating precursor carbohydrates. 

PMID- 26306703
TI  - Commentary on Moodley S et al. "Shouldn't Propranolol be Used to Treat All
      Hemangiomas?".
AB  - I was asked to provide a commentary for "Shouldn't Propranolol be Used to Treat
      All Hemangiomas?" by Moodley et al. (Aesth Plast Surg, 2015. doi: 10.1007/s00266
      015-0557-x ). I commend the authors for implicitly recognizing that it is no
      longer appropriate to take the laissez faire approach to hemangiomas of infancy.
      Whilst hemangiomas will eventually improve, they will not necessarily
      "disappear," as parents are often erroneously counseled. In fact, the larger a
      hemangioma becomes, the less likely one will be pleased with the ultimate result,
      whether treated medically or not. The natural process of proliferation followed
      by involution often produces saggy anetoderma, which, in certain anatomic
      locations is obvious and draws negative attention. NO LEVEL ASSIGNED: This
      journal requires that authors assign a level of evidence to each submission to
      which Evidence-Based Medicine rankings are applicable. This excludes Review
      Articles, Book Reviews, and manuscripts that concern Basic Science, Animal
      Studies, Cadaver Studies, and Experimental Studies. For a full description of
      these Evidence-Based Medicine ratings, please refer to the Table of Contents or
      the online Instructions to Authors http://www.springer.com/00266.

PMID- 26306704
TI  - Periorbital Lipogranuloma Following Facial Autologous Fat Injections: Non
      surgical Treatment.
AB  - BACKGROUND: Periorbital lipogranuloma following autologous fat injection into the
      forehead for cosmetic facial augmentation is a recently described adverse
      outcome. Patients have typically been treated with surgical excision. This study
      evaluates the clinical characteristics of periorbital lipogranulomas, and the non
      surgical treatment outcomes of these patients. METHODS: This is a noncomparative,
      interventional case series. A retrospective analysis of clinical data and
      radiographic images was performed of patients with periorbital lipogranuloma
      following autologous fat injection. Objective treatment outcomes after
      intralesional triamcinolone injection and/or oral prednisolone were evaluated by
      measuring the size of the lipogranulomas pre- and post-treatment. Cosmetic
      outcomes were also assessed by the subjective satisfaction at the last visit.
      RESULTS: Twenty-seven patients were identified with periorbital lipogranuloma
      following facial autologous fat injection. All patients were female, the mean age
      was 40 +/- 10 years, and 19 patients received cryopreserved fat. Twenty-one
      patients underwent non-surgical corticosteroid treatment. 'Resolution' was
      achieved in 15 patients (71%), and 'Partial Resolution' was achieved in 5
      patients (24%). One patient (5%) who took oral prednisone alone showed 'No
      Response'. Cosmetic outcomes were classified as 'Very Satisfied' in 16 patients
      (76%), 'Satisfied' in 4 patients (19%), and 'Dissatisfied' in 1 patient (5%)
      after corticosteroid treatment. CONCLUSION: Periorbital lipogranuloma following
      autologous fat injection may be diagnosed by history, physical exam, and orbital
      imaging. Non-surgical corticosteroid treatments showed a good response with few
      adverse effects and should be considered as a first line of treatment of
      periorbital granulomas prior to conducting surgical excision. LEVEL OF EVIDENCE
      IV: This journal requires that authors assign a level of evidence to each
      article. For a full description of these Evidence-Based Medicine ratings, please
      refer to the Table of Contents or the online Instructions to Authors
      www.springer.com/00266.

PMID- 26306706
TI  - Nuclear translocation of nuclear factor kappa B is regulated by G protein
      signaling pathway in arsenite-induced apoptosis in HBE cell line.
AB  - Arsenite is a certainly apoptosis inducer in various cell types. However, the
      detailed mechanism underlying how arsenite trigger apoptosis remains elusive. In
      this study, using human bronchial epithelial cell as a culture system, we
      demonstrated that arsenite-induced nuclear translocation of nuclear factor kappa
      B (NF-kappaB) resulted in the release of cytochrome c, the modulation of Fas and
      FasL, caspase activation, and ultimately leading to cell apoptosis. Importantly,
      we showed for the first time that the NF-kappaB-mediated apoptosis induced by
      arsenite was regulated by G protein-adenylate cyclase (AC)-cyclic adenosine
      monophosphate (cAMP)-protein kinase A (PKA) pathway. Inhibition of this classical
      G protein signaling pathway by a typical PKA inhibitor, H-89, caused the
      inactivation of NF-kappaB, the depletion of caspase-3, 8 and 9 activities, and
      thus reducing the level of cell apoptosis. Taken together, our results indicate
      that arsenite is able to trigger cell apoptosis in human bronchial epithelial
      cells through the nuclear translocation of NF-kappaB, which can be modulated by G
      protein signaling pathway. These findings further suggest that inhibition of G
      protein-mediated pathway by specific inhibitors may be a potential strategy for
      the prevention of arsenite toxicity. (c) 2015 Wiley Periodicals, Inc. Environ
      Toxicol 31: 1819-1833, 2016.

PMID- 26306705
TI  - Obstetric fistula in low-resource countries: an under-valued and under-studied
      problem--systematic review of its incidence, prevalence, and association with
      stillbirth.
AB  - BACKGROUND: Obstetric fistula (OF) is a serious consequence of prolonged,
      obstructed labor in settings where emergency obstetric care is limited, but there
      are few reliable, population-based estimates of the rate of OF. Stillbirth (SB)
      is another serious consequence of prolonged, obstructed labor, yet the frequency
      of SB in women with OF is poorly described. Here, we review these data. METHODS:
      We searched electronic databases and grey literature for articles on OF in low
      resource countries published between January 1, 1995, and November 16, 2014, and
      selected for inclusion 19 articles with original population-based OF incidence or
      prevalence data and 44 with reports of frequency of SB associated with OF.
      RESULTS: OF estimates came from medium- and low-HDI countries in South Asia and
      Africa, and varied considerably; incidence estimates ranged from 0 to 4.09 OF
      cases per 1000 deliveries, while prevalence estimates were judged more prone to
      bias and ranged from 0 to 81.0 OF cases per 1000 women. Reported frequency of SB
      associated with OF ranged from 32.3 % to 100 %, with estimates from the largest
      studies around 92 %. Study methods and quality were inconsistent. CONCLUSIONS:
      Reliable data on OF and associated SB in low-resource countries are lacking,
      underscoring the relative invisibility of these issues. Sound numbers are needed
      to guide policy and funding responses to these neglected conditions of poverty.

PMID- 26306707
TI  - Autism spectrum disorder in Phelan-McDermid syndrome: initial characterization
      and genotype-phenotype correlations.
AB  - BACKGROUND: Phelan-McDermid syndrome (PMS) is a neurodevelopmental disorder
      associated with a terminal deletion affecting chromosome 22 (22q13) that results
      in the loss of function of the SHANK3 gene. SHANK3 has also been identified in
      gene-linkage studies to be associated with autism spectrum disorder (ASD).
      Diagnosis of ASD in individuals with PMS is complicated by the presence of
      moderate to profound global developmental delay/intellectual disability as well
      as other co-morbid systemic and neurological symptoms. METHODS: The current study
      aimed to characterize the symptoms of ASD in patients with PMS and to do a
      preliminary exploration of genotype-ASD phenotype correlations. We conducted a
      standardized interview with 40 parents/guardians of children with PMS. Further,
      we conducted analyses on the relationship between disruption of SHANK3 and
      adjacent genes on specific characteristic symptoms of ASD in PMS in small subset
      of the sample. RESULTS: The majority of PMS participants in our sample displayed
      persistent deficits in Social communication, but only half met diagnostic
      criteria under the restricted, repetitive patterns of behavior, interests, or
      activities domain. Furthermore, logistic regressions indicated that general
      developmental delay significantly contributed to the ASD diagnosis. The analyses
      relating the PMS genotype to the behavioral phenotype revealed additional complex
      relationships with contributions of genes in both deleted and preserved SHANK3
      regions to the ASD phenotype and other neurobehavioral impairments. CONCLUSIONS:
      There appears to be a unique behavioral phenotype associated with ASD in
      individuals with PMS. There also appears to be contributions of genes in both
      deleted and preserved SHANK3 regions to the ASD phenotype and other
      neurobehavioral impairments. Better characterization of the behavioral phenotype
      using additional standardized assessments and further analyses exploring the
      relationship between the PMS genotype and behavioral phenotype in a larger sample
      are warranted.

PMID- 26306708
TI  - Gut feelings of safety: tolerance to the microbiota mediated by innate immune
      receptors.
AB  - To enable microbial colonization of the gut mucosa, the intestinal immune system
      must not only react to danger signals but also recognize cues that indicate
      safety. Recognition of safety, paradoxically, is mediated by the same
      environmental sensors that are involved in signaling danger. Indeed, in addition
      to their well-established role in inducing inflammation in response to stress
      signals, pattern recognition receptors and a variety of metabolic sensors also
      promote gut-microbiota symbiosis by responding to "microbial symbiosis factors",
      "resolution-associated molecular patterns", markers of energy extraction and
      other signals indicating the absence of pathogenic infection and tissue damage.
      Here we focus on how the paradoxical roles of immune receptors and other
      environmental sensors define the microbiota signature of an individual. 

PMID- 26306709
TI  - Modulation of Gut Microbiota-Brain Axis by Probiotics, Prebiotics, and Diet.
AB  - There exists a bidirectional communication system between the gastrointestinal
      tract and the brain. Increasing evidence shows that gut microbiota can play a
      critical role in this communication; thus, the concept of a gut microbiota and
      brain axis is emerging. Here, we review recent findings in the relationship
      between intestinal microbes and brain function, such as anxiety, depression,
      stress, autism, learning, and memory. We highlight the advances in modulating
      brain development and behavior by probiotics, prebiotics, and diet through the
      gut microbiota-brain axis. A variety of mechanisms including immune, neural, and
      metabolic pathways may be involved in modulation of the gut microbiota-brain
      axis. We also discuss some future challenges. A deeper understanding of the
      relationship between the gut bacteria and their hosts is implicated in developing
      microbial-based therapeutic strategies for brain disorders. 

PMID- 26306710
TI  - Utility of a New Spanish RQC and PSC in Screening with CBCL Validation.
AB  - Various screening questionnaires have been established to identify
      psychopathology in children and adolescents. Some of these instruments include
      the pediatric symptom checklist (PSC), the pediatric symptom checklist (CBCL) and
      reporting questionnaire for children (RQC). However, many of the patients and
      their families may not speak English, and this can be a barrier to identifying
      and properly treating monolingual Spanish-speaking patients and families. There
      is a need for optimal mental health screening in Spanish speaking populations
      given the continued growth of the United States as a diverse country with complex
      demographic structure. Because of the diversity within the use of Spanish in
      Hispanic countries of origin, the aim of this study is to present unified Spanish
      versions of the RQC and PSC achieved through simultaneously and independently
      translating them into three versions of Spanish (RQC-SP and PSC-SP). To test the
      psychiatric validity of RQC-SP and PSC-SP, these both were administered
      simultaneously along with the Spanish version of the CBCL, which had already been
      well established. All three of these tools were given to Spanish speaking parents
      of pediatric outpatients (n = 22) while waiting for their clinic appointments.
      The RQC-SP had a correlation to the CBCL with R = 0.779 and p < 0.001. The RQC-SP
      as compared with the CBCL had a false negative of 0/8 (0.00) with a sensitivity
      of 8/8 = 1.00. The false positives were 2/14 (0.143) and specificity 12/15
      (0.85). The PSC-SP correlated with the CBCL with R = 0.897 and p < 0.001. The PSC
      SP correlation with the CBCL had false negative of 7/8 (0.875) and sensitivity of
      1/8 (0.125) and false positive 0/14 (0.00) and specificity 14/14 (1.00). The RQC
      SP and PSC-SP are brief, well-validated, reliable instruments designed.

PMID- 26306711
TI  - NSAIDs and cardiovascular disease: time to say no to diclofenac.

PMID- 26306712
TI  - Engineering catechol 1, 2-dioxygenase by design for improving the performance of
      the cis, cis-muconic acid synthetic pathway in Escherichia coli.
AB  - Regulating and ameliorating enzyme expression and activity greatly affects the
      performance of a given synthetic pathway. In this study, a new synthetic pathway
      for cis, cis-muconic acid (ccMA) production was reconstructed without exogenous
      induction by regulating the constitutive expression of the important enzyme
      catechol 1,2-dioxygenase (CatA). Next, new CatAs with significantly improved
      activities were developed to enhance ccMA production using structure-assisted
      protein design. Nine mutations were designed, simulated and constructed based on
      the analysis of the CatA crystal structure. These results showed that mutations
      at Gly72, Leu73 and/or Pro76 in CatA could improve enzyme activity, and the
      activity of the most effective mutant was 10-fold greater than that of the wild
      type CatA from Acinetobacter sp. ADP1. The most productive synthetic pathway with
      a mutated CatA increased the titer of ccMA by more than 25%. Molecular dynamic
      simulation results showed that enlarging the entrance of the substrate-binding
      pocket in the mutants contributed to their increased enzyme activities and thus
      improved the performance of the synthetic pathway. 

PMID- 26306713
TI  - Proficiency testing in immunohistochemistry--experiences from Nordic
      Immunohistochemical Quality Control (NordiQC).
AB  - Despite extensive use of immunohistochemistry (IHC) for decades, lack of
      standardization remains a major problem, even aggravated in the era of targeted
      therapy. Nordic Immunohistochemical Quality Control (NordiQC) is an international
      academic proficiency testing (PT) program established in 2003 primarily aimed at
      assessing the analytical phases of the laboratory IHC quality. About 700
      laboratories from 80 countries are currently participating. More than 30,000 IHC
      slides have been evaluated during 2003-2015. Overall, about 20 % of the staining
      results in the breast cancer IHC module and about 30 % in the general module have
      been assessed as insufficient for diagnostic use. The most common causes for
      insufficient results are less successful antibodies (poor and less robust
      antibodies, poorly calibrated ready-to-use (RTU) products, and stainer platform
      dependent antibodies; 17 %), insufficiently calibrated antibody dilutions (20 %),
      insufficient or erroneous epitope retrieval (27 %), less sensitive visualization
      systems (19 %), and other (heat- and proteolysis-induced impaired morphology,
      endogenous biotin reaction, drying out phenomena, stainer platform-dependant
      protocol issues; 17 %). Approximately, 90 % of the insufficient results are
      characterized by either a too weak or false negative staining, whereas in the
      remaining 10 %, a poor signal-to-noise ratio or false positive staining is seen.
      Individually tailored recommendations for protocol optimization and
      identification of best tissue controls to ensure appropriate calibration of the
      IHC assay have for many markers improved IHC staining as well as inter-laboratory
      consistency of the IHC results. RTUs will not always provide an optimal result
      and data sheets frequently misguide the laboratories hampering the improvement in
      IHC quality. The overall data generated by NordiQC during 12 years indicates that
      continuous PT is valuable and necessary. Detailed description of the results of
      the NordiQC programme is available on www.nordiqc.org and summarized in this
      paper.

PMID- 26306714
TI  - Quality improvement in basic histotechnology: the lean approach.
AB  - Lean is a comprehensive system of management based on the Toyota production
      system (TPS), encompassing all the activities of an organization. It focuses
      management activity on creating value for the end-user by continuously improving
      operational effectiveness and removing waste. Lean management creates a culture
      of continuous quality improvement with a strong emphasis on developing the
      problem-solving capability of staff using the scientific method (Deming's Plan,
      Do, Check, Act cycle). Lean management systems have been adopted by a number of
      histopathology departments throughout the world to simultaneously improve quality
      (reducing errors and shortening turnround times) and lower costs (by increasing
      efficiency). This article describes the key concepts that make up a lean
      management system, and how these concepts have been adapted from manufacturing
      industry and applied to histopathology using a case study of lean implementation
      and evidence from the literature. It discusses the benefits, limitations, and
      pitfalls encountered when implementing lean management systems.

PMID- 26306715
TI  - Endorsing good quality assurance practices in molecular pathology: risks and
      recommendations for diagnostic laboratories and external quality assessment
      providers.
AB  - Quality assurance is an indispensable element in a molecular diagnostic
      laboratory. The ultimate goal is to warrant patient safety. Several risks that
      can compromise high quality procedures are at stake, from sample collection to
      the test performed by the laboratory, the reporting of test results to
      clinicians, and the organization of effective external quality assessment
      schemes. Quality assurance should therefore be safeguarded at each level and
      should imply a holistic multidisciplinary approach. This review aims to provide
      an overview of good quality assurance practices and discusses certain risks and
      recommendations to promote and improve quality assurance for both diagnostic
      laboratories and for external quality assessment providers. The number of
      molecular targets is continuously rising, and new technologies are evolving. As
      this poses challenges for clinical implementation and increases the demand for
      external quality assessment, the formation of an international association for
      improving quality assurance in molecular pathology is called for. 

PMID- 26306716
TI  - Multidisciplinary rehabilitation treatment versus cognitive behavioural therapy
      for patients with chronic fatigue syndrome: a randomized controlled trial.
AB  - OBJECTIVES: The aim of this trial was to evaluate the difference in treatment
      effect, at 26 and 52 weeks after the start of treatment, between cognitive
      behavioural therapy (CBT) and multidisciplinary rehabilitation treatment (MRT)
      for patients with chronic fatigue syndrome (CFS). DESIGN: Multicentre, randomized
      controlled trial of patients with CFS. Participants were randomly assigned to MRT
      or CBT. SETTING: Four rehabilitation centres in the Netherlands. SUBJECTS: A
      total of 122 patients participated in the trial. MAIN OUTCOME MEASURES: Primary
      outcomes were fatigue measured by the fatigue subscale of the Checklist
      Individual Strength and health-related quality of life measured by the Short-Form
      36. Outcomes were assessed prior to treatment and at 26 and 52 weeks after
      treatment initiation. RESULTS: A total of 114 participants completed the
      assessment at 26 weeks, and 112 completed the assessment at 52 weeks. MRT was
      significantly more effective than CBT in reducing fatigue at 52 weeks. The
      estimated difference in fatigue between the two treatments was -3.02 [95%
      confidence interval (CI) -8.07 to 2.03; P = 0.24] at 26 weeks and -5.69 (95% CI 
      10.62 to -0.76; P = 0.02) at 52 weeks. Patients showed an improvement in quality
      of life over time, but between-group differences were not significant.
      CONCLUSION: This study provides evidence that MRT is more effective in reducing
      long-term fatigue severity than CBT in patients with CFS. Although implementation
      in comparable populations can be recommended based on clinical effectiveness, it
      is advisable to analyse the cost-effectiveness and replicate these findings in
      another multicentre trial.

PMID- 26306717
TI  - Geometric discord: A resource for increments of quantum key generation through
      twirling.
AB  - In the present work, we consider a scenario where an arbitrary two-qubit pure
      state is applied for the quantum key generation (QKG). Using the twirling
      procedure to convert the pure state into a Werner state, the error rate of the
      key can be reduced by a factor of 2/3. This effect indicates that entanglement is
      not the sufficient resource of QKG protocol since it is not increased in the
      twirling procedure. Based on the fact that the geometric discord is increased in
      the twirling procedure, we argue that the geometric discord should be taken as a
      necessary resource for the QKG task. Besides the pure state, we also give other
      two types of mixtures where twirling may increase the discord and reduce the
      error rate of the generated key. 

PMID- 26306718
TI  - Dengue infection with multiorgan dysfunction: SOFA score, arterial lactate and
      serum albumin levels are predictors of outcome.

PMID- 26306720
TI  - Direct transfer of long-stay ICU patients to a nursing-home rehabilitation unit:
      focus on functional dependency.

PMID- 26306719
TI  - Recovery after critical illness in patients aged 80 years or older: a multi
      center prospective observational cohort study.
AB  - PURPOSE: Increasingly, very old patients are admitted to Intensive Care Units
      (ICUs). The objective of this study was to describe 12-month outcomes of these
      patients and determine which characteristics are associated with a return to
      baseline physical function 1 year later. METHODS: In this prospective cohort
      study in 22 Canadian hospitals, we recruited 610 patients aged 80 years or older
      who were admitted to ICU for at least 24 h. At baseline, we completed a
      comprehensive geriatric assessment and followed patients to determine 12-month
      survival and physical function. Our primary outcome was physical recovery from
      critical illness at 12 months, defined as being alive with Short Form-36 physical
      function score of at least 10 points, and not 10 or more points below baseline.
      We used regression analysis to examine factors associated with physical recovery.
      RESULTS: Patients were on average 84 years old (range 80-99). Mortality was 14%
      in ICU, 26% in hospital and 44% at 12 months after admission. Of 505 patients
      evaluable at 12 months, 26% achieved physical recovery. In the multivariable
      model, physical recovery was significantly associated with younger age, lower
      APACHE II score, lower Charlson comorbidity score, lower frailty index, lower
      baseline physical function score, and specific admission diagnoses. CONCLUSIONS:
      One-quarter of patients aged 80 years or older who are admitted to ICU survived
      and returned to baseline levels of physical function at 1 year. Routine
      assessment of baseline physical function and frailty status could aid in
      prognostication and informed decision-making for very old critically ill
      patients. (ClinicalTrials.gov number NCT01293708).

PMID- 26306721
TI  - The prevalence of benign prostatic hyperplasia in mainland China: evidence from
      epidemiological surveys.
AB  - The epidemiological characteristics of benign prostate hyperplasia (BPH) in
      mainland China are not completely understood. We performed this meta-analysis to
      assess the prevalence of BPH from 1989 through 2014. A total of 14 articles and
      19 datasets were included. The pooled overall prevalence of BPH among men aged 40
      years and older was 36.6% [95% CI, 32.3-44.8]. The occurrence rate of BPH in the
      age groups 40-49 years, 50-59 years, 60-69 years, 70-79 years and 80 years and
      older was 2.9%, 29.0%, 44.7%, 58.1% and 69.2%, respectively. The pooled
      occurrence rate of BPH was 41.5% [95% CI, 34.5-48.4] in urban areas and 38.6%
      [95% CI, 22.7-54.6] in rural areas; this difference in prevalence was not
      statistically significant [OR, 1.51; 95% CI, 0.97-2.36]. BPH is highly prevalent
      in mainland China, and its prevalence increased with age. The trend in the
      prevalence of BPH in mainland China was not steady; the prevalence map based on a
      geographic information system (GIS) showed an unequal geographic distribution.
      High-quality surveys on BPH with a larger sample size are needed throughout
      mainland China to confirm these findings. 

PMID- 26306722
TI  - Electricity generation by Propionibacterium freudenreichii in a mediatorless
      microbial fuel cell.
AB  - OBJECTIVE: To test Propionibacterium freudenreichii as a novel biocatalyst in a
      glycerol-oxidizing microbial fuel cell (MFC). RESULTS: Two strains, P.
      freudenreichii ssp. shermanii and P. freudenreichii ssp. freudenreichii, were
      screened as anodic biocatalysts and shown to produce power from glycerol in an
      MFC. Voltage was generated with and without resazurin in the medium, showing that
      both strains are exoelectrogenic. Polarization data showed that an MFC with P.
      freudenreichii ssp. shermanii reached a maximum open circuit voltage of 485 mV
      and a maximum power density of 14.9 mW m(-2). Glycerol consumption was about 50 %
      lower in MFCs than in fermentations, indicating a metabolic shift in the MFC
      environment. CONCLUSION: P. freudenreichii ssp. shermanii and P. freudenreichii
      ssp. freudenreichii were shown for the first time to act as exoelectrogenic
      anodic biocatalysts in MFCs.

PMID- 26306724
TI  - Corrigendum: Real sequence effects on the search dynamics of transcription
      factors on DNA.

PMID- 26306723
TI  - Processing of voided urine for prostate cancer RNA biomarker analysis.
AB  - BACKGROUND: Voided urine samples have been shown to contain cells released from
      prostate tumors. Could good quality RNA from cells in urine be obtained from
      every donor for multimarker analysis? In addition, could urine donation be as
      simple as possible, a practical consideration for a lab test, without involving a
      prostate massage (as indicated for PCA3 testing), which precludes frequent
      collection; needing it done at a specific time of day (e.g., first or second
      urine); and requiring prompt processing of samples in clinics with limited
      molecular biology capability? METHODS: Collected urine samples were pelleted, and
      the RNA isolated was processed for cDNA synthesis and in vitro transcription to
      generate amplified sense aRNA. The resultant aRNA was rigorously analyzed for
      possible introduced changes. DMSO was used as a cell preservative for frozen
      storage of urine samples. RESULTS: Good quality aRNA was obtained for over 100
      samples collected at two different institutions. The process of RNA amplification
      removed co-isolated DNA in some samples, which did not affect RNA amplification.
      Amplification did not amplify genes that were absent and produce other expression
      alterations. The sense aRNA could be used to generate urinary transcriptomes
      specific to individual patients. No chaotropic agents for RNA preservation were
      added to the urine samples so that the supernatant could be used for analysis of
      secreted protein biomarkers. The time of donation was not important since
      patients were seen during the entire day. DMSO was an effective cell preservative
      for freezing urine. CONCLUSIONS: Urinary RNA can be readily isolated and
      amplified for prostate cancer biomarker analysis. Individual patients had unique
      set of transcripts derived from their tumor.

PMID- 26306725
TI  - Pathological, biochemical, and biophysical characteristics of the transthyretin
      variant Y114H (p.Y134H) explain its very mild clinical phenotype.
AB  - Transthyretin (TTR) is a homotetrameric protein that must misfold in order to
      form amyloid fibrils. Misfolding includes rate limiting tetramer dissociation,
      followed by fast tertiary structural changes of the monomer that enable
      aggregation. Hereditary ATTR amyloidosis is an autosomal dominant genetic
      disorder with systemic deposition of amyloid fibrils induced by TTR gene
      mutation. We identified a rare Y114H (p.Y134H) TTR variant in a Japanese patient
      presenting with late-onset, very mild clinical course. The patient had an
      extremely low serum variant TTR concentration (18% of total TTR), whereas the
      composition of variant TTR was 55% in amyloid fibrils in tenosynovial tissues
      obtained at carpal tunnel release surgery. The amyloid fibril deposits in the
      ATTR Y114H patient had an altered structure compared with that in wild-type ATTR
      patients, as determined by luminescent conjugated poly/oligo-thiophene
      fluorescence spectroscopy. Biophysical studies using recombinant protein showed
      that Y114H TTR was markedly destabilized both thermodynamically and kinetically
      and was highly amyloidogenic in vitro. These data suggest that extremely low
      serum variant Y114H TTR concentration, probably due to endoplasmic reticulum
      associated degradation of unstable variant TTR protein, protected this patient
      from severe amyloidosis, as self-assembly of the amyloidogenic intermediate is a
      concentration-dependent process. 

PMID- 26306726
TI  - Clinical impact on ovarian cancer patients of massive parallel sequencing for
      BRCA mutation detection: the experience at Gemelli hospital and a literature
      review.
AB  - OBJECTIVE: Massive parallel sequencing (MPS) is the new frontier for molecular
      diagnostics. Twenty-four papers regarding BRCA analysis were considered for
      reviewing all pipelines evaluated in this field. METHODS: Proposed here is an
      integrated MPS workflow able to successfully identify BRCA1/2 mutational status
      on 212 Italian ovarian cancer patients. The review of literature data is
      reported. RESULT: The pipeline can be routinely used as robust molecular
      diagnostic strategy, being highly sensitive and specific. CONCLUSION: Literature
      data report that efforts are being made in order to fully translate MPS-based
      BRCA1/2 gene assay into routine clinical diagnostics. However, this study
      highlights the need of an integrated MPS BRCA1/2 molecular workflow fulfilling
      the standardized requirements needed in the routine clinical laboratory practice.

PMID- 26306728
TI  - Extra-anatomic iliac to superior mesenteric artery bypass after bridge
      endovascular treatment for chronic mesenteric ischemia. A case report.
AB  - A 60 year old patient presenting chronic mesenteric Ischemia (CMI) was managed
      with superior mesenteric artery (SMA) stenting as bridge therapy to conventional
      open surgery. At 5 months follow-up, the SMA stent occluded. During this bridge
      period the patient gained his general condition and the body mass index (BMI)
      increased from 18 to 22. The patient was managed subsequently with iliac-SMA
      bypass in C-loop configuration. At 6 months follow-up the bypass is patent, the
      patient has no CMI symptoms and his BMI is 25. The endovascular approach did not
      preclude a subsequent conventional open surgery and it can be safely employed as
      bridge therapy. An improved patient clinical condition, also during a limited
      bridge period, can improve the conventional open surgery outcomes. KEY WORDS:
      Body Mass Index(BMI), Mesenteric artery, Mesenteric ischemia.

PMID- 26306727
TI  - Serum adiponectin in HIV-1 and hepatitis C virus mono- and co-infected Kenyan
      injection drug users.
AB  - Adiponectin is an important marker of anthropometric profiles of adipose tissue.
      However, association of adiponectin and adiposity in HIV mono- and co-infected
      and hepatitis (HCV) injection drug users (IDUs) has not been elucidated.
      Therefore, the relationship of total adiponectin levels with anthropometric
      indices of adiposity was examined in HIV mono-infected (anti-retroviral
      treatment, ART-naive, n=16 and -experienced, n=34); HCV mono-infected, n=36; HIV
      and HCV co-infected (ART-naive, n=5 and -experienced, n=13); uninfected, n=19
      IDUs; and healthy controls, n=16 from coastal Kenya. Anthropometric indices of
      adiposity were recorded and total circulating adiponectin levels were measured in
      serum samples using enzyme-linked immunosorbent assay. Adiponectin levels
      differed significantly amongst the study groups (P<0.0001). Post-hoc analyses
      revealed decreased levels in HIV mono-infected ART-naive IDUs in comparison to
      uninfected IDUs (P<0.05) and healthy controls (P<0.05). However, adiponectin
      levels were elevated in HCV mono-infected IDUs relative to HIV mono-infected ART
      naive (P<0.001) and -experienced (P<0.001) as well as HIV and HCV co-infected ART
      naive (P<0.05) IDUs. Furthermore, adiponectin correlated with weight (rho=0.687;
      P=0.003) and BMI (rho=0.598; P=0.014) in HIV mono-infected ART-naive IDUs; waist
      circumference (rho=-0.626; P<0.0001), hip (rho=-0.561; P=0.001) circumference,
      and bust-to-waist ratio (rho=0.561; P=0.001) in HIV mono-infected ART-experienced
      IDUs; waist girth (rho=0.375; P=0.024) in HCV mono-infected IDUs; and waist-to
      hip ratio (rho=-0.872; P=0.048) in HIV and HCV co-infected ART-naive IDUs.
      Altogether, these results suggest suppression of adiponectin production in
      treatment-naive HIV mono-infected IDUs and that circulating adiponectin is a
      useful surrogate marker of altered adiposity in treatment-naive and -experienced
      HIV and HCV mono- and co-infected IDUs. 

PMID- 26306729
TI  - Variation in mate-recognition pheromones of the fungal genus Microbotryum.
AB  - Mate recognition is an essential life-cycle stage that exhibits strong
      conservation in function, whereas diversification of mating signals can
      contribute directly to the integrity of species boundaries through assortative
      mating. Fungi are simple models, where compatibility is based on the recognition
      of pheromone peptides by corresponding receptor proteins, but clear patterns of
      diversification have not emerged from the species examined, which are few
      compared with mate signaling studies in plant and animal systems. In this study,
      candidate loci from Microbotryum species were used to characterize putative
      pheromones that were synthesized and found to be functional across multiple
      species in triggering a mating response in vitro. There is no significant
      correlation between the strength of a species' response and its genetic distance
      from the pheromone sequence source genome. Instead, evidence suggests that
      species may be strong or weak responders, influenced by environmental conditions
      or developmental differences. Gene sequence comparisons reveals very strong
      purifying selection on the a1 pheromone peptide and corresponding receptor, but
      significantly less purifying selection on the a2 pheromone peptide that
      corresponds with more variation across species in the receptor. This represents
      an exceptional case of a reciprocally interacting mate-recognition system in
      which the two mating types are under different levels of purifying selection. 

PMID- 26306730
TI  - Does population size affect genetic diversity? A test with sympatric lizard
      species.
AB  - Genetic diversity is a fundamental requirement for evolution and adaptation.
      Nonetheless, the forces that maintain patterns of genetic variation in wild
      populations are not completely understood. Neutral theory posits that genetic
      diversity will increase with a larger effective population size and the
      decreasing effects of drift. However, the lack of compelling evidence for a
      relationship between genetic diversity and population size in comparative studies
      has generated some skepticism over the degree that neutral sequence evolution
      drives overall patterns of diversity. The goal of this study was to measure
      genetic diversity among sympatric populations of related lizard species that
      differ in population size and other ecological factors. By sampling related
      species from a single geographic location, we aimed to reduce nuisance variance
      in genetic diversity owing to species differences, for example, in mutation rates
      or historical biogeography. We compared populations of zebra-tailed lizards and
      western banded geckos, which are abundant and short-lived, to chuckwallas and
      desert iguanas, which are less common and long-lived. We assessed population
      genetic diversity at three protein-coding loci for each species. Our results were
      consistent with the predictions of neutral theory, as the abundant species almost
      always had higher levels of haplotype diversity than the less common species.
      Higher population genetic diversity in the abundant species is likely due to a
      combination of demographic factors, including larger local population sizes (and
      presumably effective population sizes), faster generation times and high rates of
      gene flow with other populations.

PMID- 26306731
TI  - The process of developing a community-based research agenda with lesbian, gay,
      bisexual, transgender and queer youth in the Northwest Territories, Canada.
AB  - BACKGROUND: Youth in Canada's Northwest Territories (NWT) experience sexual and
      mental health disparities. Higher rates of sexual and mental health concerns
      among lesbian, gay, bisexual, transgender and queer (LGBTQ) youth in comparison
      with heterosexual and cisgender peers have been associated with stigma and
      discrimination. Although LGBTQ youth in the NWT are situated at the nexus of
      Northern and LGBTQ health disparities, there is little known about their health,
      well-being and experiences of stigma. This short communication discusses the
      process of developing a LGBTQ youth community-based research programme in the
      NWT. METHODS: We developed an interdisciplinary research team of LGBTQ and allied
      young adults, including indigenous and non-indigenous researchers, community
      organisers and service providers in the NWT. We conducted meetings in Yellowknife
      with LGBTQ youth (n=12) and key stakeholders (n=15), including faculty, students,
      community groups and health and social service providers. Both meetings included
      LGBTQ and allied participants who were LGBTQ, indigenous, youth and persons at
      the intersection of these identities. RESULTS: LGBTQ youth participants discussed
      community norms that devalued same sex identities and stigma surrounding LGBTQ
      specific services and agencies. Stigma among LGBT youth was exacerbated for youth
      in secondary schools, gender non-conforming and transgender youth and young gay
      men. In the stakeholder meeting, service providers discussed the importance of
      integrating LGBTQ issues in youth programmes, and LGBTQ community groups
      expressed the need for flexibility in service delivery to LGBTQ youth.
      Stakeholders identified the need to better understand the needs of indigenous
      LGBTQ youth in the NWT. CONCLUSIONS: Community-based LGBTQ groups, researchers
      and health and social service providers are interested in addressing LGBTQ youth
      issues in the NWT. The emergence of LGBTQ community building, support groups and
      activism in Northern Canada suggests that this is an opportune time to explore
      LGBTQ youth health.

PMID- 26306732
TI  - Portrayal of sustainability principles in the mission statements and on home
      pages of the world's largest organizations.
AB  - Conservation can be achieved only if sustainability is embraced as core to
      organizational cultures. To test the extent to which the related concepts of
      sustainability, conservation, response to climate change, poverty alleviation,
      and gender equity have been incorporated into organizational culture, we compared
      mission statements published from 1990 to 2000 with those published in 2014 for
      150 organizations, including conservation nongovernmental organizations (NGOs),
      aid NGOs, government development agencies, resource extraction companies, and
      retailers (30 in each category). We also analyzed the 2014 home web pages of each
      organization. Relative to the earlier period, the frequency with which mission
      statements mentioned poverty alleviation, biodiversity conservation, and a range
      of sustainable practices increased only slightly by 2014, particularly among
      resource extractors and retail companies. Few organizations in any sector had
      embedded either climate change or gender equity into their mission statements. In
      addition, the proportional intensity with which any of the aspirations were
      expressed did not change between periods. For current home pages, conservation
      NGOs, resource extractors, and government agencies were significantly more likely
      to acknowledge the importance of matters that were not part of their core
      business, but few aid agencies or retail companies promoted goals beyond
      alleviation of crises and profit maximization, respectively. Overall, there has
      been some progress in recognizing poverty alleviation, biodiversity conservation,
      and sustainable practices, but gender equity and a determination to reduce
      impacts on climate change are still rarely promoted as central institutional
      concerns. Sustainability in general, and biodiversity conservation in particular,
      will not be achieved unless their importance is more widely apparent in core
      communication products of organizations.

PMID- 26306733
TI  - Norwegian constraint-induced therapy multisite trial: adherence to treatment
      protocol applied early after stroke.
AB  - OBJECTIVE: To investigate to what degree patients adhered to a modified
      constraint-induced movement therapy protocol, and to explore factors associated
      with the results. DESIGN: Prospective follow-up of the intervention arm in a
      randomized controlled trial. SUBJECTS: Twenty-four patients within 28 days after
      stroke. METHODS: The protocol specified 180 min of treatment/day for 10 days.
      Therapy schedules were used to calculate the time spent in shaping, task practice
      and transfer package, as well as movement quality, perceived exertion and
      treatment progression. RESULTS: The participants spent a mean of 91.3% of the
      intended time for treatment. Time spent practicing tasks was 30 min less than the
      intended 150 min, whereas slightly more time than intended was spent on the
      transfer package. Of the time spent in shaping, 33% was spent in pure activity.
      The remainder was used on feedback, task set-up, and rests. Adherence was
      positively associated with treatment progression (r = 0.74) and negatively
      associated with age (r = -0.65). Women were less likely to use the mitt (r = 
      0.55). CONCLUSION: Overall adherence was good; however, time spent in motor
      activity was only one-third of total treatment time. The parameters in the
      constraint-induced movement therapy protocol should be individually adjusted
      early after stroke.

PMID- 26306734
TI  - New directions for drug-resistant breast cancer: the CDK4/6 inhibitors.
AB  - Many breast cancers are treated with selective estrogen receptor modulators
      (SERMs) if the cancers are estrogen and progesterone hormone receptor positive.
      However, some 30% are not responsive or later become resistant to such therapies.
      There has been continued interest in developing new and more effective SERMs that
      target the estrogen receptors for therapeutic benefit. This article will focus on
      therapies directed against other molecular targets to improve outcomes, as
      preventing growth of breast cancer cells by an unrelated mechanism is most likely
      to yield success against resistance, or synergize in a combination therapy with
      SERMs or aromatase inhibitors. New drugs in development that target the cyclin
      dependent kinases CDK4/CDK6 have 'breakthrough therapy' designation at the US FDA
      and may provide an exciting and realistic new avenue to patients in the near
      future. 

PMID- 26306735
TI  - Respiratory Therapist Job Perceptions: The Impact of Protocol Use.
AB  - BACKGROUND: Demand for respiratory care services and staffing levels of
      respiratory therapists (RTs) is expected to increase over the next several years.
      Hence, RT job satisfaction will be a critical factor in determining recruitment
      and retention of RTs. Determinants of RT job satisfaction measures have received
      little attention in the literature. This study examines the use of respiratory
      care protocols and associated levels of RT job satisfaction, turnover intentions,
      and job stress. METHODS: Four-hundred eighty-one RTs at 44 hospitals responded to
      an online survey regarding job satisfaction, turnover intentions, and job stress.
      Random coefficient modeling was used for analysis and to account for the nested
      structure of the data. RESULTS: Higher levels of RT protocol use were associated
      with higher levels of job satisfaction, lower rates of turnover intentions, and
      lower levels of job stress. In addition, RTs with greater experience had higher
      levels of job satisfaction, and RTs working at teaching hospitals had lower rates
      of turnover intentions. CONCLUSIONS: The study extends prior research by
      examining how the use of respiratory care protocols favorably affects RTs'
      perceptions of job satisfaction, turnover intention, and job stress. In a time of
      increasing demand for respiratory care services, protocols may enhance retention
      of RTs.

PMID- 26306736
TI  - Effects of Arm Bracing on Expiratory Flow Limitation and Lung Volume in Elderly
      COPD Subjects.
AB  - BACKGROUND: Although it is useful for COPD patients to relieve their dyspnea by
      bracing their arms, the relationships between the arm bracing posture and
      expiratory flow limitation (EFL) and lung volume are unknown. Whether arm bracing
      affects dyspnea, EFL, and lung volume in elderly COPD patients was investigated.
      METHODS: Sixteen elderly subjects (median [interquartile range] age 81 [77-85] y)
      with stable COPD (percent-of-predicted FEV1 50.9 [31.3-64.9] %) and 16 age
      matched healthy subjects were studied. Breathing patterns, EFL, lung volume, SpO2
      , and heart rate during quiet breathing were randomly evaluated in 3 standing
      postures: erect, leaning forward, and arm bracing. Dyspnea was also assessed for
      each posture with a Borg dyspnea score at the end of the test. RESULTS: Lung
      volume was significantly higher with arm bracing than with the other postures in
      both groups (P < .05). Breathing patterns, SpO2 , and pulse rate were not
      significantly different among the 3 postures in both groups. However, EFL and
      Borg dyspnea scores were significantly lower with arm bracing than with the other
      postures in COPD subjects (P < .01). CONCLUSIONS: The decreased EFL in the arm
      bracing position may be caused by breathing at a higher lung volume than in the
      erect position, which may be one of the factors relieving dyspnea in elderly COPD
      patients.

PMID- 26306737
TI  - Thermodynamics of substrate binding to the metal site in homoprotocatechuate 2,3
      dioxygenase: Using ITC under anaerobic conditions to study enzyme-substrate
      interactions.
AB  - BACKGROUND: Extradiol dioxygenases are a family of nonheme iron (and sometimes
      manganese) enzymes that catalyze an O2-dependent ring-opening reaction in a
      biodegradation pathway of aromatic compounds. Here we characterize the
      thermodynamics of two substrates binding in homoprotocatechuate 2,3-dioxygenase
      (HPCD) prior to the O2 activation step. METHODS: This study uses microcalorimetry
      under an inert atmosphere to measure thermodynamic parameters associated with
      catechol binding to nonheme metal centers in HPCD. Several stopped-flow rapid
      mixing experiments were used to support the calorimetry experiments. RESULTS: The
      equilibria constant for 4-nitrocatechol and homoprotocatechuate binding to the
      iron(II) and manganese(II) forms of HPCD range from 2*10(4) to 1*10(6),
      suggesting there are distinctive differences in how the enzyme-substrate
      complexes are stabilized. Further experiments in multiple buffers allowed us to
      correct the experimental DeltaH for substrate ionization and to fully derive the
      pH and buffer independent thermodynamic parameters for substrate binding to HPCD.
      Fewer protons are released from the iron(II) dependent processes than their
      manganese(II) counterparts. CONCLUSIONS: Condition independent thermodynamic
      parameters for 4-nitrocatechol and homoprotocatechuate binding to HPCD are highly
      consistent with each other, suggesting these enzyme-substrate complexes are more
      similar than once thought, and the ionization state of metal coordinated waters
      may be playing a role in tuning redox potential and in governing reactivity.
      GENERAL SIGNIFICANCE: Substrate binding to HPCD is a complex set of equilibria
      that includes ionization of substrate and water release, yet it is also the key
      step in O2 activation.

PMID- 26306738
TI  - Pre-treatment mean platelet volume associates with worse clinicopathologic
      features and prognosis of patients with invasive breast cancer.
AB  - BACKGROUND: Mean platelet volume (MPV) is one of the four platelet parameters
      (platelet count, MPV, platelet distribution width and plateletcrit), which
      indicates the activation of platelet. We aim to investigate the associations
      between pre-treatment MPV levels and clinical hematology parameters, pathology
      parameters and prognosis of patients with invasive breast cancer (IBC). METHODS:
      Medical records of 340 breast tumor patients (170 IBC vs. 170 breast benign
      tumor) were retrospectively reviewed. Patients in two groups were matched for
      age, body mass index, smoking status and complications. To analyze: differences
      in pre-treatment MPV levels between IBC group and breast benign tumor group;
      differences between pre- and postoperative MPV levels in IBC patients;
      correlations between pre-treatment MPV and clinical hematology parameters,
      clinicopathologic parameters and prognosis in IBC patients. RESULTS: As we
      analyzed, pre-treatment MPV levels of IBC patients were significantly higher than
      the controls (8.65 +/- 0.98 vs 8.34 +/- 0.78, P = 0.002), and preoperative MPV
      levels were significantly higher than the postoperative in IBC patients (8.65 +/-
      0.98 vs 8.44 +/- 0.91, P = 0.042). In IBC group, pre-treatment MPV level
      associated, significantly, with clinical hematology parameters (platelet,
      fibrinogen, albumin, fasting blood glucose, P = 0.003, 0.042, 0.032, 0.046,
      respectively) and with clinicopathological parameters (distant metastasis,
      primary tumor size, tumor node metastasis stages, P = 0.039, 0.002, 0.001,
      respectively). Furthermore, univariate and multivariate survival analysis
      demonstrated that MPV was significant prognostic factor (P = 0.035, HR 1.86, 95 %
      confidence interval 1.06-3.25). CONCLUSION: High pre-treatment MPV level in IBC
      patients was a potential predictive factor and significant independent prognostic
      factor.

PMID- 26306739
TI  - Secreted aspartic protease 2 of Candida albicans inactivates factor H and the
      macrophage factor H-receptors CR3 (CD11b/CD18) and CR4 (CD11c/CD18).
AB  - The opportunistic pathogenic yeast Candida albicans employs several mechanisms to
      interfere with the human complement system. This includes the acquisition of host
      complement regulators, the release of molecules that scavenge complement proteins
      or block cellular receptors, and the secretion of proteases that inactivate
      complement components. Secreted aspartic protease 2 (Sap2) was previously shown
      to cleave C3b, C4b and C5. C. albicans also recruits the complement inhibitor
      factor H (FH), but yeast-bound FH can enhance the antifungal activity of human
      neutrophils via binding to complement receptor type 3 (CR3). In this study, we
      characterized FH binding to human monocyte-derived macrophages. Inhibition
      studies with antibodies and siRNA targeting CR3 (CD11b/CD18) and CR4
      (CD11c/CD18), as well as analysis of colocalization of FH with these integrins
      indicated that both function as FH receptors on macrophages. Preincubation of C.
      albicans yeast cells with FH induced increased production of IL-1beta and IL-6 in
      macrophages. Furthermore, FH enhanced zymosan-induced production of these
      cytokines. C. albicans Sap2 cleaved FH, diminishing its complement regulatory
      activity, and Sap2-treatment resulted in less detectable CR3 and CR4 on
      macrophages. These data show that FH enhances the activation of human macrophages
      when bound on C. albicans. However, the fungus can inactivate both FH and its
      receptors on macrophages by secreting Sap2, which may represent an additional
      means for C. albicans to evade the host innate immune system. 

PMID- 26306740
TI  - Levels of uric acid may predict the future development of pulmonary hypertension
      in systemic lupus erythematosus: a seven-year follow-up study.
AB  - OBJECTIVE: The objective of this paper is to assess whether pulmonary
      hypertension (PH) may be detected at one point in time or longitudinally
      predicted by serum uric acid (sUA) levels in systemic lupus erythematosus (SLE).
      METHODS: We conducted a post-hoc analysis of a long-term followed cohort of
      Mexican SLE patients. Echocardiography-based definitions of PH by the
      ESC/ERS/ISHLT and its associations with clinical and laboratory data on
      enrollment were studied. Especially, the impact that sUA levels at baseline may
      have on the future development of PH in patients with normal pulmonary artery
      systolic pressure (PASP) was explored. RESULTS: Out of the 156 SLE patients
      originally enrolled in the cohort, 44 met the inclusion criteria for the present
      study and were grouped as having (n =10) or not having (n = 34) PH. At baseline,
      sUA levels of 5.83 +/- 1.79 and 5.82 +/- 1.97 mg/dl (p = ns) were found in
      patients with and without PH, respectively. No association between PASP and other
      markers was found. In patients with normal PASP, the presence of sUA >= 7 mg/dl
      at baseline predicted future development of PH (relative risk 8.5, 1.0009 to 72;
      p = 0.04). CONCLUSION: In SLE, sUA levels at one point in time are useless to
      detect PH. However, steady hyperuricemia may predict the future development of PH
      in patients with normal PASP at baseline.

PMID- 26306741
TI  - Acquired enophthalmos with systemic lupus erythematosus.
AB  - Ocular involvement sometimes occurs with systemic lupus erythematosus (SLE) but
      enophthalmos with SLE is rare. We report a case of enophthalmos with SLE. A 25
      year-old male was admitted for two weeks of fever, sore throat, arthralgia, chest
      pain and right arm weakness with pain. We diagnosed him with SLE with malar rash,
      arthritis, pleural effusion, proteinuria, leukopenia, positive antinuclear
      antibody, anti-dsDNA, and lupus anticoagulant. The patient was prescribed high
      dose prednisolone and hydroxychloroquine 400 mg. One week after discharge, he
      complained about a sensation of a sunken right eye. CT showed right enophthalmos,
      a post-inflammatory change and chronic inflammation. Proteinuria increased to 3.8
      g/day after the patient stopped taking prednisolone. Cyclophosphamide therapy was
      administered for three months without improvement. We decided to restart
      prednisolone and change cyclophosphamide to mycophenolate mofetil. Proteinuria
      decreased but enophthalmos remains as of this reporting.

PMID- 26306742
TI  - Terrestrial origin of bacterial communities in complex boreal freshwater
      networks.
AB  - Bacteria inhabiting boreal freshwaters are part of metacommunities where local
      assemblages are often linked by the flow of water in the landscape, yet the
      resulting spatial structure and the boundaries of the network metacommunity have
      never been explored. Here, we reconstruct the spatial structure of the bacterial
      metacommunity in a complex boreal aquatic network by determining the taxonomic
      composition of bacterial communities along the entire terrestrial/aquatic
      continuum, including soil and soilwaters, headwater streams, large rivers and
      lakes. We show that the network metacommunity has a directional spatial structure
      driven by a common terrestrial origin of aquatic communities, which are
      numerically dominated by taxa recruited from soils. Local community assembly is
      driven by variations along the hydrological continuum in the balance between mass
      effects and species sorting of terrestrial taxa, and seems further influenced by
      priority effects related to the spatial sequence of entry of soil bacteria into
      the network.

PMID- 26306743
TI  - Mitigative Effects of a Combination of Multiple Pharmaceutical Drugs on the
      Survival of Mice Exposed to Lethal Ionizing Radiation.
AB  - It is important to establish an easy-to-use therapeutic protocol for the
      emergency medical care of patients involved in radiation accidents to reduce the
      radiation-related casualties. The present study aimed to establish an optimum
      therapeutic protocol using currently approved pharmaceutical drugs to increase
      the survival of victims exposed to lethal radiation. Different combinations of
      four drugs-recombinant human erythropoietin (EPO), granulocyte-colony stimulating
      factor (G-CSF), c-mpl receptor agonist romiplostim (RP) and nandrolone decanoate
      (ND)-were administered to mice within 2 h after exposure to a lethal 7 Gy dose of
      gamma-irradiation. On day 30 after irradiation, the condition of the mice was
      analyzed using various hematological parameters, such as the number of peripheral
      blood cells, bone marrow cells, hematopoietic progenitor cells and the expression
      of cell surface antigens. Approximately 10% of the untreated irradiated control
      mice survived for 21 days, but all of the control mice died by day 30. The
      combined administration of G-CSF, EPO and RP for five days immediately after
      irradiation led to a complete survival of the irradiated mice until day 30.
      However, the treatment with G-CSF, EPO and RP with ND led to only 75% survival at
      day 30. The hematological analyses showed that the numbers of almost all of
      hematopoietic cells in the surviving mice treated with effective medications
      recovered to the levels of non-irradiated mice. The present findings show that
      the combination of G-CSF, EPO and RP may be a useful countermeasure for victims
      exposed to accidental lethal irradiation. 

PMID- 26306744
TI  - Induction of Oral Tolerance with Transgenic Plants Expressing Antigens for
      Prevention/Treatment of Autoimmune, Allergic and Inflammatory Diseases.
AB  - The prevalence and incidence of autoimmune and allergic diseases have increased
      dramatically over the last several decades, especially in the developed world.
      The treatment of autoimmune and allergic diseases is typically with the use of
      non-specific immunosuppressive agents that compromise the integrity of the host
      immune system and therefore, increase the risk of infections. Antigenspecific
      immunotherapy by reinstating immunological tolerance towards self antigens
      without compromising immune functions is a much desired goal for the treatment of
      autoimmune and allergic diseases. Mucosal administration of antigen is a long
      recognized method of inducing antigen-specific immune tolerance known as oral
      tolerance, which is viewed as having promising potential in the treatment of
      autoimmune and allergic diseases. Plant-based expression and delivery of
      recombinant antigens provide a promising new platform to induce oral tolerance,
      having considerable advantages including reduced cost and increased safety.
      Indeed, in recent years the use of tolerogenic plants for oral tolerance
      induction has attracted increasing attention, and considerable progress has been
      made. This review summarizes recent advances in using plants to deliver
      tolerogens for induction of oral tolerance in the treatment of autoimmune,
      allergic and inflammatory diseases. 

PMID- 26306745
TI  - Cyanobacteria as a Source for Novel Anti-Leukemic Compounds.
AB  - Cyanobacteria are an inspiring source of bioactive secondary metabolites. These
      bioactive agents are a diverse group of compounds which are varying in their
      bioactive targets, the mechanisms of action, and chemical structures.
      Cyanobacteria from various environments, especially marine benthic cyanobacteria,
      are found to be rich sources for the search for novel bioactive compounds.
      Several compounds with anticancer activities have been discovered from
      cyanobacteria and some of these have succeeded to enter the clinical trials.
      Varying anticancer agents are needed to overcome increasing challenges in cancer
      treatments. Different search methods are used to reveal anticancer compounds from
      natural products, but cell based methods are the most common. Cyanobacterial
      bioactive compounds as agents against acute myeloid leukemia are not well
      studied. Here we examined our new results combined with previous studies of anti
      leukemic compounds from cyanobacteria with emphasis to reveal common features in
      strains producing such activity. We report that cyanobacteria harbor specific
      anti-leukemic compounds since several studied strains induced apoptosis against
      AML cells but were inactive against non-malignant cells like hepatocytes. We
      noted that particularly benthic strains from the Baltic Sea, such as Anabaena
      sp., were especially potential AML apoptosis inducers. Taken together, this
      review and re-analysis of data demonstrates the power of maintaining large
      culture collections for the search for novel bioactivities, and also how anti-AML
      activity in cyanobacteria can be revealed by relatively simple and low-cost
      assays. 

PMID- 26306746
TI  - The Crosstalk between Tissue Engineering and Pharmaceutical Biotechnology: Recent
      Advances and Future Directions.
AB  - Tissue-engineered constructs made of biotechnology-derived materials have been
      preferred due to their chemical and physical composition, which offers both high
      versatility and a support to enclose/ incorporate relevant signaling molecules
      and/or genes known to therapeutically induce tissue repair. Herein, a critical
      overview of the impact of different biotechnology-derived materials, scaffolds,
      and recombinant signaling molecules over the behavior of cells, another element
      of tissue engineered constructs, as well its regulatory role in tissue
      regeneration and disease progression is given. Additionally, these tissue
      engineered constructs evolved to three-dimensional (3D) tissue-like models that,
      as an advancement of two-dimensional standard culture methods, are expected to be
      a valuable tool in the field of drug discovery and pharmaceutical research.
      Despite the improved design and conception of current proposed 3D tissue-like
      models, advanced control systems to enable and accelerate streamlining and
      automation of the numerous labor-intensive steps intrinsic to the development of
      tissue-engineered constructs are still to be achieved. In this sense, this review
      intends to present the biotechnology- derived materials that are being explored
      in the field of tissue engineering to generate 3D tissue-analogues and briefly
      highlight their foremost breakthroughs in tissue regeneration and drug discovery.
      It also aims to reinforce that the crosstalk between tissue engineering and
      pharmaceutical biotechnology has been fostering the outcomes of tissue
      engineering approaches through the use of biotechnology-derived signaling
      molecules. Gene delivery/therapy is also discussed as a forefront area that
      represents another cross point between tissue engineering and pharmaceutical
      biotechnology, in which nucleic acids can be considered a "super pharmaceutical"
      to drive biological responses, including tissue regeneration. 

PMID- 26306747
TI  - Evaluation of Anti-aging Compounds Using the Promoters of Elastin and Fibrillin-1
      Genes Combined with a Secreted Alkaline Phosphatase Reporter in Normal Human
      Fibroblasts.
AB  - Elastic fibers are major constituents of the extracellular matrix (ECM) in
      dynamic tissues in the human body, and regulation of elastin and fibrillin-1
      expression mediates the formation of these fibers. Traditional assays for the
      measurement of elastin and fibrillin-1, such as western blotting, Luna staining
      and immunostaining, are relatively complex and time-consuming. Thus, a relatively
      simple assay system that also provides rational results is urgently needed. In
      the study, we aimed to develop a human cell-based assay system that can be used
      to analyze functional compounds using the promoters of elastin (ELN) and
      fibrillin-1 (FBN1) genes integrated with a secreted alkaline phosphatase (SEAP)
      reporter in normal human fibroblast cells. We used this system to assess anti
      aging compounds. We used several regulators of elastinogenesis, including
      retinol, coenzyme Q10, deoxyArbutin and Elestan(TM) (Manilkara multinervis leaf
      extract), to verify the efficacy of this assay system. Our results demonstrate
      that this assay system can be used as a fast and realistic method for identifying
      anti-aging components for future use in foods, cosmetics and drugs. 

PMID- 26306750
TI  - Dual role of RsmA in the coordinated regulation of expression of virulence genes
      in Pectobacterium wasabiae strain SCC3193.
AB  - The CsrA/RsmA family of post-transcriptional regulators in bacteria is involved
      in regulating many cellular processes, including pathogenesis. Using a
      bioinformatics approach, we identified an RsmA binding motif, A(N)GGA, in the
      Shine-Dalgarno regions of 901 genes. Among these genes with the predicted RsmA
      binding motif, 358 were regulated by RsmA according to our previously published
      gene expression profiling analysis (WT vs rsmA negative mutant; Koiv et al.,
      2013). A small subset of the predicted targets known to be important as virulence
      factors was selected for experimental validation. RNA footprint analyses
      demonstrated that RsmA binds specifically to the ANGGA motif in the 5'UTR
      sequences of celV1, pehA, pelB, pel2 and prtW. RsmA-dependent regulation of these
      five genes was examined in vivo using plasmid-borne translational and
      transcriptional fusions with a reporter gusA gene. They were all affected
      negatively by RsmA. However, we demonstrated that whereas the overall effect of
      RsmA on celV1 and prtW was determined on both the translational and
      transcriptional level, expression of pectinolytic enzyme genes (pehA, pel2 and
      pelB) was affected mainly on the level of transcription in tested conditions. In
      summary, these data indicate that RsmA controls virulence by integration of its
      regulatory activities at various levels. 

PMID- 26306751
TI  - Selective Targeting of the KRAS Codon 12 Mutation Sequence by Pyrrole-Imidazole
      Polyamide seco-CBI Conjugates.
AB  - Mutation of KRAS is a key step in many cancers. Mutations occur most frequently
      at codon 12, but the targeting of KRAS is notoriously difficult. We recently
      demonstrated selective reduction in the volume of tumors harboring the KRAS codon
      12 mutation in a mouse model by using an alkylating hairpin N-methylpyrrole-N
      methylimidazole polyamide seco-1,2,9,9a-tetrahydrocyclopropa[1,2-c]benz[1,2
      e]indol-4-one conjugate (conjugate 4) designed to target the KRAS codon 12
      mutation sequence. Herein, we have compared the alkylating activity of 4 against
      three other conjugates that were also designed to target the KRAS codon 12
      mutation sequence. Conjugate 4 displayed greater affinity for the G12D mutation
      sequence than for the G12V sequence. A computer-minimized model suggested that
      conjugate 4 could bind more efficiently to the G12D match sequence than to a one
      base-pair mismatch sequence. Conjugate 4 was modified for next-generation
      sequencing. Bind-n-Seq analysis supported the evidence showing that conjugate 4
      could target the G12D mutation sequence with exceptionally high affinity and the
      G12V mutation sequence with much higher affinity than that for the wild-type
      sequence.

PMID- 26306748
TI  - Global Cell Proteome Profiling, Phospho-signaling and Quantitative Proteomics for
      Identification of New Biomarkers in Acute Myeloid Leukemia Patients.
AB  - The identification of protein biomarkers for acute myeloid leukemia (AML) that
      could find applications in AML diagnosis and prognosis, treatment and the
      selection for bone marrow transplant requires substantial comparative analyses of
      the proteomes from AML patients. In the past years, several studies have
      suggested some biomarkers for AML diagnosis or AML classification using methods
      for sample preparation with low proteome coverage and low resolution mass
      spectrometers. However, most of the studies did not follow up, confirm or
      validate their candidates with more patient samples. Current proteomics methods,
      new high resolution and fast mass spectrometers allow the identification and
      quantification of several thousands of proteins obtained from few tens of MUg of
      AML cell lysate. Enrichment methods for posttranslational modifications (PTM),
      such as phosphorylation, can isolate several thousands of site-specific
      phosphorylated peptides from AML patient samples, which subsequently can be
      quantified with high confidence in new mass spectrometers. While recent reports
      aiming to propose proteomic or phosphoproteomic biomarkers on the studied AML
      patient samples have taken advantage of the technological progress, the access to
      large cohorts of AML patients to sample from and the availability of appropriate
      control samples still remain challenging. 

PMID- 26306749
TI  - Systems analysis of host-parasite interactions.
AB  - Parasitic diseases caused by protozoan pathogens lead to hundreds of thousands of
      deaths per year in addition to substantial suffering and socioeconomic decline
      for millions of people worldwide. The lack of effective vaccines coupled with the
      widespread emergence of drug-resistant parasites necessitates that the research
      community take an active role in understanding host-parasite infection biology in
      order to develop improved therapeutics. Recent advances in next-generation
      sequencing and the rapid development of publicly accessible genomic databases for
      many human pathogens have facilitated the application of systems biology to the
      study of host-parasite interactions. Over the past decade, these technologies
      have led to the discovery of many important biological processes governing
      parasitic disease. The integration and interpretation of high-throughput -omic
      data will undoubtedly generate extraordinary insight into host-parasite
      interaction networks essential to navigate the intricacies of these complex
      systems. As systems analysis continues to build the foundation for our
      understanding of host-parasite biology, this will provide the framework necessary
      to drive drug discovery research forward and accelerate the development of new
      antiparasitic therapies.

PMID- 26306752
TI  - Association of Intraplaque Hemorrhage and Acute Infarction in Patients With
      Basilar Artery Plaque.
AB  - BACKGROUND AND PURPOSE: High-resolution magnetic resonance imaging (HRMRI) is
      ideal for serial examination of diseased arterial walls because it is noninvasive
      and has superior capability of discriminating tissue characteristics. The aim of
      this study is to evaluate the prevalence and clinical relevance of intraplaque
      hemorrhage (IPH) in patients with basilar artery (BA) atherosclerosis using
      HRMRI. METHODS: We analyzed HRMRI and clinical data from 74 patients (45
      symptomatic and 29 asymptomatic), all of whom had >50% BA stenosis. High-signal
      intensity within a BA plaque on magnetization-prepared rapid acquisition with
      gradient-echo was defined as an area with an intensity that was >150% of the
      signal from the adjacent muscle. The relationship between IPH within a BA plaque
      region and clinical presentation was analyzed. RESULTS: Thirty patients were
      positive for IPH on HRMRI (42.3%, 24 symptomatic and 6 asymptomatic). Symptomatic
      lesions in the MR-positive IPH group were significantly more prevalent than in
      the MR-negative group (80.0% versus 48.8%; P<0.01). Also, MR-predicted IPH was
      significantly more prevalent in the high-grade stenosis group (P<0.001) than in
      the low-grade group. The relative risk of an acute focal stroke event among
      patients who were magnetization-prepared rapid acquisition with gradient-echo
      positive for IPH compared with patients who were magnetization-prepared rapid
      acquisition with gradient-echo-negative was 1.64. CONCLUSIONS: IPH within a BA
      plaque region on HRMRI is highly prevalent and is associated with acute stroke.

PMID- 26306754
TI  - Predicting Collateral Status With Magnetic Resonance Perfusion Parameters:
      Probabilistic Approach With a Tmax-Derived Prediction Model.
AB  - BACKGROUND AND PURPOSE: Good collateral flow is an important predictor for
      favorable responses to recanalization therapy and successful outcomes after acute
      ischemic stroke. Magnetic resonance perfusion-weighted imaging (MRP) is widely
      used in patients with stroke. However, it is unclear whether the perfusion
      parameters and thresholds would predict collateral status. The present study
      evaluated the relationship between hypoperfusion severity and collateral status
      to develop a predictive model for good collaterals using MRP parameters. METHODS:
      Patients who were eligible for recanalization therapy that underwent both serial
      diffusion-weighted imaging and serial MRP were enrolled into the study. A
      collateral flow map derived from MRP source data was generated through automatic
      postprocessing. Hypoperfusion severity, presented as proportions of every 2-s
      Tmax strata to the entire hypoperfusion volume (Tmax>=2 s), was compared between
      patients with good and poor collaterals. Prediction models for good collaterals
      were developed with each Tmax strata proportion and cerebral blood volumes.
      RESULTS: Among 66 patients, 53 showed good collaterals based on MRP-based
      collateral grading. Although no difference was noted in delays within 16 s, more
      severe Tmax delays (Tmax16-18 s, Tmax18-22 s, Tmax22-24 s, and Tmax>24 s) were
      associated with poor collaterals. The probability equation model using Tmax
      strata proportion demonstrated high predictive power in a receiver operating
      characteristic analysis (area under the curve=0.9303; 95% confidence interval,
      0.8682-0.9924). The probability score was negatively correlated with the volume
      of infarct growth (P=0.030). CONCLUSIONS: Collateral status is associated with
      more severe Tmax delays than previously defined. The present Tmax severity
      weighted model can determine good collaterals and subsequent infarct growth.

PMID- 26306755
TI  - Comparison of the 2 Most Popular Deconvolution Techniques for the Detection of
      Penumbral Flow in Acute Stroke.
AB  - BACKGROUND AND PURPOSE: Dynamic susceptibility-weighted contrast-enhanced (DSC)
      magnetic resonance imaging (MRI) is used to identify the tissue-at-risk in acute
      stroke, but the choice of optimal DSC postprocessing in the clinical setting
      remains a matter of debate. Using 15O-water positron emission tomography (PET),
      we validated the performance of 2 common deconvolution methods for DSC-MRI.
      METHODS: In (sub)acute stroke patients with consecutive MRI and PET imaging, DSC
      maps were calculated applying 2 deconvolution methods, standard and block
      circulant single value decomposition. We used 2 standardized analysis methods, a
      region of interest-based and a voxel-based analysis, where PET cerebral blood
      flow masks of <20 mL/100 g per minute (penumbral flow) and gray matter masks were
      overlaid on DSC parameter maps. For both methods, receiver operating
      characteristic curve analysis was performed to identify the accuracy of each DSC
      MR map for the detection of PET penumbral flow. RESULTS: In 18 data sets (median
      time after stroke onset: 18 hours; median time PET to MRI: 101 minutes), block
      circulant single value decomposition showed significantly better performance to
      detect PET penumbral flow only for mean transit time maps. Time-to-maximum (Tmax)
      had the highest performance independent of the deconvolution method. CONCLUSIONS:
      Block-circulant single value decomposition seems only significantly beneficial
      for mean transit time maps in (sub)acute stroke. Tmax is likely the most stable
      deconvolved parameter for the detection of tissue-at-risk using DSC-MRI.

PMID- 26306753
TI  - PD-L1 Monoclonal Antibody Treats Ischemic Stroke by Controlling Central Nervous
      System Inflammation.
AB  - BACKGROUND AND PURPOSE: Both pathogenic and regulatory immune processes are
      involved in the middle cerebral artery occlusion (MCAO) model of experimental
      stroke, including interactions involving the programmed death 1 (PD-1) receptor
      and its 2 ligands, PD-L1 and PD-L2. Although PD-1 reduced stroke severity, PD-L1
      and PD-L2 appeared to play pathogenic roles, suggesting the use of anti-PD-L
      monoclonal antibody therapy for MCAO. METHODS: Male C57BL/6 mice were treated
      with a single dose of anti-PD-L1 monoclonal antibody 4 hours after MCAO and
      evaluated for clinical, histological and immunologic changes after 96 hours of
      reperfusion. RESULTS: Blockade of the PD-L1 checkpoint using a single injection
      of 200 MUg anti-PD-L1 monoclonal antibody given intravenously 4 hours after
      occlusion significantly reduced MCAO infarct volumes and improved neurological
      outcomes after 96 hours of reperfusion. Treatment partially reversed splenic
      atrophy and decreased central nervous system infiltrating immune cells
      concomitant with enhanced appearance of CD8(+) regulatory T cells in the lesioned
      central nervous system hemisphere. CONCLUSIONS: This study demonstrates for the
      first time the beneficial therapeutic effects of PD-L1 checkpoint blockade on
      MCAO, thus validating proposed mechanisms obtained in our previous studies using
      PD-1- and PD-L-deficient mice. These results provide strong support for the use
      of available humanized anti-PD-L1 antibodies for treatment of human stroke
      subjects.

PMID- 26306756
TI  - Influenza A(H5N8) virus isolation in Russia, 2014.
AB  - In this study, we report the isolation of influenza A(H5N8) virus from a Eurasian
      wigeon (Anas penelope) in Sakha Republic of the Russian Far East. The strain
      A/wigeon/Sakha/1/2014 (H5N8) has been shown to be pathogenic for mammals. It is
      similar to the strains that caused outbreaks in wild birds and poultry in
      Southeast Asia and Europe in 2014. 

PMID- 26306757
TI  - India's problem with toxic alcohol.

PMID- 26306758
TI  - Mechanisms and kinetics of granulated sewage sludge combustion.
AB  - This paper investigates sewage sludge disposal methods with particular emphasis
      on combustion as the priority disposal method. Sewage sludge incineration is an
      attractive option because it minimizes odour, significantly reduces the volume of
      the starting material and thermally destroys organic and toxic components of the
      off pads. Additionally, it is possible that ashes could be used. Currently, as
      many as 11 plants use sewage sludge as fuel in Poland; thus, this technology must
      be further developed in Poland while considering the benefits of co-combustion
      with other fuels. This paper presents the results of experimental studies aimed
      at determining the mechanisms (defining the fuel combustion region by studying
      the effects of process parameters, including the size of the fuel sample,
      temperature in the combustion chamber and air velocity, on combustion) and
      kinetics (measurement of fuel temperature and mass changes) of fuel combustion in
      an air stream under different thermal conditions and flow rates. The combustion
      of the sludge samples during air flow between temperatures of 800 and 900 degrees
      C is a kinetic-diffusion process. This process determines the sample size,
      temperature of its environment, and air velocity. The adopted process parameters,
      the time and ignition temperature of the fuel by volatiles, combustion time of
      the volatiles, time to reach the maximum temperature of the fuel surface, maximum
      temperature of the fuel surface, char combustion time, and the total process
      time, had significant impacts. 

PMID- 26306759
TI  - Targeting a host-cell entry factor barricades antiviral-resistant HCV variants
      from on-therapy breakthrough in human-liver mice.
AB  - OBJECTIVE: Direct-acting antivirals (DAAs) inhibit hepatitis C virus (HCV)
      infection by targeting viral proteins that play essential roles in the
      replication process. However, selection of resistance-associated variants (RAVs)
      during DAA therapy has been a cause of therapeutic failure. In this study, we
      wished to address whether such RAVs could be controlled by the co-administration
      of host-targeting entry inhibitors that prevent intrahepatic viral spread.
      DESIGN: We investigated the effect of adding an entry inhibitor (the anti
      scavenger receptor class B type I mAb1671) to a DAA monotherapy (the protease
      inhibitor ciluprevir) in human-liver mice chronically infected with HCV of
      genotype 1b. Clinically relevant non-laboratory strains were used to achieve
      viraemia consisting of a cloud of related viral variants (quasispecies) and the
      emergence of RAVs was monitored at high resolution using next-generation
      sequencing. RESULTS: HCV-infected human-liver mice receiving DAA monotherapy
      rapidly experienced on-therapy viral breakthrough. Deep sequencing of the HCV
      protease domain confirmed the manifestation of drug-resistant mutants upon viral
      rebound. In contrast, none of the mice treated with a combination of the DAA and
      the entry inhibitor experienced on-therapy viral breakthrough, despite detection
      of RAV emergence in some animals. CONCLUSIONS: This study provides preclinical in
      vivo evidence that addition of an entry inhibitor to an anti-HCV DAA regimen
      restricts the breakthrough of DAA-resistant viruses. Our approach is an excellent
      strategy to prevent therapeutic failure caused by on-therapy rebound of DAA-RAVs.
      Inclusion of an entry inhibitor to the newest DAA combination therapies may
      further increase response rates, especially in difficult-to-treat patient
      populations.

PMID- 26306760
TI  - Metal or plastic stents for preoperative biliary drainage in resectable
      pancreatic cancer.
AB  - INTRODUCTION: In pancreatic cancer, preoperative biliary drainage (PBD) increases
      complications compared with surgery without PBD, demonstrated by a recent
      randomised controlled trial (RCT). This outcome might be related to the plastic
      endoprosthesis used. Metal stents may reduce the PBD-related complications risk.
      METHODS: A prospective multicentre cohort study was performed including patients
      with obstructive jaundice due to pancreatic cancer, scheduled to undergo PBD
      before surgery. This cohort was added to the earlier RCT (ISRCTN31939699). The
      RCT protocol was adhered to, except PBD was performed with a fully covered self
      expandable metal stent (FCSEMS). This FCSEMS cohort was compared with the RCT's
      plastic stent cohort. PBD-related complications were the primary outcome. Three
      group comparison of overall complications including early surgery patients was
      performed. RESULTS: 53 patients underwent PBD with FCSEMS compared with 102
      patients treated with plastic stents. Patients' characteristics did not differ.
      PBD-related complication rates were 24% in the FCSEMS group vs 46% in the plastic
      stent group (relative risk of plastic stent use 1.9, 95% CI 1.1 to 3.2, p=0.011).
      Stent-related complications (occlusion and exchange) were 6% vs 31%. Surgical
      complications did not differ, 40% vs 47%. Overall complication rates for the
      FCSEMS, plastic stent and early surgery groups were 51% vs 74% vs 39%.
      CONCLUSIONS: For PBD in pancreatic cancer, FCSEMS yield a better outcome compared
      with plastic stents. Although early surgery without PBD remains the treatment of
      choice, FCSEMS should be preferred over plastic stents whenever PBD is indicated.
      TRIAL REGISTRATION NUMBER: Dutch Trial Registry (NTR3142).

PMID- 26306762
TI  - Enhancing students' learning in problem based learning: validation of a self
      assessment scale for active learning and critical thinking.
AB  - BACKGROUND: Problem based learning (PBL) is a powerful learning activity but
      fidelity to intended models may slip and student engagement wane, negatively
      impacting learning processes, and outcomes. One potential solution to solve this
      degradation is by encouraging self-assessment in the PBL tutorial. Self
      assessment is a central component of the self-regulation of student learning
      behaviours. There are few measures to investigate self-assessment relevant to PBL
      processes. We developed a Self-assessment Scale on Active Learning and Critical
      Thinking (SSACT) to address this gap. We wished to demonstrated evidence of its
      validity in the context of PBL by exploring its internal structure. METHODS: We
      used a mixed methods approach to scale development. We developed scale items from
      a qualitative investigation, literature review, and consideration of previous
      existing tools used for study of the PBL process. Expert review panels evaluated
      its content; a process of validation subsequently reduced the pool of items. We
      used structural equation modelling to undertake a confirmatory factor analysis
      (CFA) of the SSACT and coefficient alpha. RESULTS: The 14 item SSACT consisted of
      two domains "active learning" and "critical thinking." The factorial validity of
      SSACT was evidenced by all items loading significantly on their expected factors,
      a good model fit for the data, and good stability across two independent samples.
      Each subscale had good internal reliability (>0.8) and strongly correlated with
      each other. CONCLUSIONS: The SSACT has sufficient evidence of its validity to
      support its use in the PBL process to encourage students to self-assess. The
      implementation of the SSACT may assist students to improve the quality of their
      learning in achieving PBL goals such as critical thinking and self-directed
      learning.

PMID- 26306763
TI  - PAPP-A affects tendon structure and mechanical properties.
AB  - Pregnancy-associated plasma protein-A (PAPP-A) serves to increase local insulin
      like growth factor (IGF) stimulation of proliferation and differentiation in many
      tissues through proteolysis of inhibitory IGF-binding proteins. The purpose of
      this study was to investigate the effects of PAPP-A on tendon structure and
      mechanical properties. A total of 30 tails from 6-month-old mice were tested with
      10 tails in each of following groups: PAPP-A knockout (KO), skeletal-specific
      PAPP-A overexpressing transgenic (Tg) and wild type (WT). Morphologically, the
      total tail cross-sectional area (CSA), individual tissue CSAs of bone, muscle and
      tendon, and fascicle diameter were measured. A fascicle pullout test was
      performed to assess stiffness and strength of interfascicular structures.
      Fascicles were mechanically characterized through low and high displacement rate
      uniaxial tension tests providing modulus at each rate, hysteresis area and stress
      relaxation ratio. The KO mice had a smaller total tail CSA (p<0.05), fascicle
      diameter (p<0.05), absolute tendon CSA (p<0.05), fast and slow stiffness (p<0.05
      for both) and larger hysteresis area (p<0.05) compared to WT and Tg mice. On the
      other hand, the Tg mice had a larger fascicle diameter (p<0.05), absolute tendon
      CSA (p<0.05), higher interfascicular strength and stiffness (p<0.05) and lower
      fascicular modulus at low displacement rates (p<0.05) compared to WT and KO mice.
      Tg mice also had larger total tail CSA area (p<0.05) and smaller hysteresis area
      (p<0.05) than KO mice, and larger normalized tendon CSA (p<0.05) than WT mice.
      Based on these data, we conclude that PAPP-A affects fascicle structure, thereby
      affecting tendon phenotype. 

PMID- 26306761
TI  - Vagal nerve stimulation started just prior to reperfusion limits infarct size and
      no-reflow.
AB  - Vagal nerve stimulation (VNS) started prior to, or during, ischemia has been
      shown to reduce infarct size. Here, we investigated the effect of VNS when
      started just prior to, and continued during early, reperfusion on infarct size
      and no-reflow and studied the underlying mechanisms. For this purpose, swine (13
      VNS, 10 sham) underwent 45 min mid-LAD occlusion followed by 120 min of
      reperfusion. VNS was started 5 min prior to reperfusion and continued until 15
      min of reperfusion. Area at risk, area of no-reflow (% of infarct area) and
      infarct size (% of area at risk), circulating cytokines, and regional myocardial
      leukocyte influx were assessed after 120 min of reperfusion. VNS significantly
      reduced infarct size from 67 +/- 2 % in sham to 54 +/- 5 % and area of no-reflow
      from 54 +/- 6 % in sham to 32 +/- 6 %. These effects were accompanied by
      reductions in neutrophil (~40 %) and macrophage (~60 %) infiltration in the
      infarct area (all p < 0.05), whereas systemic circulating plasma levels of
      TNFalpha and IL6 were not affected. The degree of cardioprotection could not be
      explained by the VNS-induced bradycardia or the VNS-induced decrease in the
      double product of heart rate and left ventricular systolic pressure. In the
      presence of NO-synthase inhibitor LNNA, VNS no longer attenuated infarct size and
      area of no-reflow, which was paralleled by similarly unaffected regional
      leukocyte infiltration. In conclusion, VNS is a promising novel adjunctive
      therapy that limits reperfusion injury in a large animal model of acute
      myocardial infarction. 

PMID- 26306764
TI  - Recruitment of beta-arrestin 1 and 2 to the beta2-adrenoceptor: analysis of 65
      ligands.
AB  - Beyond canonical signaling via Galphas and cAMP, the concept of functional
      selectivity at beta2-adrenoceptors (beta2ARs) describes the ability of adrenergic
      drugs to stabilize ligand-specific receptor conformations to initiate further
      signaling cascades comprising additional G-protein classes or beta-arrestins
      (betaarr). A set of 65 adrenergic ligands including 40 agonists and 25
      antagonists in either racemic or enantiopure forms was used for betaarr
      recruitment experiments based on a split-luciferase assay in a cellular system
      expressing beta2AR. Many agonists showed only (weak) partial agonism regarding
      betaarr recruitment. Potencies and/or efficacies increased depending on the
      number of chirality centers in (R) configuration; no (S)-configured distomer was
      more effective at inducing betaarr recruitment other than the eutomer. betaarr2
      was recruited more effectively than betaarr1. The analysis of antagonists
      revealed no significant effects on betaarr recruitment. Several agonists showed
      preference for activation of Galphas GTPase relative to betaarr recruitment, and
      no betaarr-biased ligand was identified. IN CONCLUSION: 1) agonists show strong
      bias for Galphas activation relative to betaarr recruitment; 2) agonists recruit
      betaarr1 and betaarr2 with subtle differences; and 3) there is no evidence for
      betaarr recruitment by antagonists.

PMID- 26306766
TI  - Induction of epithelial-mesenchymal transition via activation of epidermal growth
      factor receptor contributes to sunitinib resistance in human renal cell carcinoma
      cell lines.
AB  - Sunitinib is widely used for treating renal cell carcinoma (RCC). However, some
      patients do not respond to treatment with this drug. We aimed to study the
      association between sunitinib sensitivity and epithelial-mesenchymal transition
      (EMT) regulation via epidermal growth factor receptor (EGFR) signaling, which is
      a mechanism of resistance to anticancer drugs. Three RCC cell lines (786-O, ACHN,
      and Caki-1) were used, and then we evaluated cell viability, EMT regulatory
      proteins, and signal transduction with sunitinib treatment. Cell viability of 786
      O cells was maintained after treatment with sunitinib. After treatment with
      sunitinib, EGFR phosphorylation increased in 786-O cells, resulting in an
      increase in the phosphorylation of extracellular signal-regulated kinase, nuclear
      translocation of beta-catenin, and expression of mesenchymal markers. These
      results suggest that sunitinib induced EMT via activation of EGFR in 786-O cells,
      but not in ACHN and Caki-1 cells. Caki-1/SN cells, a resistant cell line
      generated by continuous exposure to sunitinib, displayed increased
      phosphorylation of EGFR. Cell viability in the presence of sunitinib was
      decreased by erlotinib, as the selective inhibitor of EGFR, treatment in 786-O
      and Caki-1/SN cells. Similarly, erlotinib suppressed sunitinib-induced EGFR
      activation and upregulated mesenchymal markers. Thus, we postulate that
      resistance to sunitinib in RCC may be associated with EMT caused by activation of
      EGFR. 

PMID- 26306767
TI  - Are Proton Pump Inhibitors Affecting Intestinal Microbiota Health?

PMID- 26306765
TI  - Fibromyalgia syndrome in need of effective treatments.
AB  - Fibromyalgia syndrome (FMS) is a chronic, idiopathic condition of widespread
      musculoskeletal pain, affecting primarily women. It is clinically characterized
      by chronic, nonarticular pain and a heightened response to pressure along with
      sleep disturbances, fatigue, bowel and bladder abnormalities, and cognitive
      dysfunction. The diagnostic criteria have changed repeatedly, and there is
      neither a definitive pathogenesis nor reliable diagnostic or prognostic
      biomarkers. Clinical and laboratory studies have provided evidence of altered
      central pain pathways. Recent evidence suggests the involvement of
      neuroinflammation with stress peptides triggering the release of neurosenzitizing
      mediators. The management of FMS requires a multidimensional approach including
      patient education, behavioral therapy, exercise, and pain management. Here we
      review recent data on the pathogenesis and propose new directions for research
      and treatment. 

PMID- 26306768
TI  - Investigation Gone Viral: Application of the Social Mediasphere in Research.

PMID- 26306770
TI  - Preventing T cell rejection of pig xenografts.
AB  - Xenotransplantation is a potential solution to the limited supply of donor
      organs. While early barriers to xenograft acceptance, such as hyperacute
      rejection, are now largely avoided through genetic engineering, the next frontier
      in successful xenograft survival will require prevention of T cell-mediated
      rejection. Most successful immunosuppressive regimens in xenotransplantation
      utilize T cell depletion with antibody therapy. Additionally, the use of T cell
      costimulatory blockade - specifically blockade of the CD40-CD154 pathway - shows
      promise with several reports of long-term xenograft survival. Additional
      therapies, such as transgenic expression of T cell coinhibitory molecules or
      transfer of immunomodulatory cells to promote tolerance, may be necessary to
      achieve reliable long-term xenograft acceptance. Further studies in pre-clinical
      models are essential in order to optimize these regimens prior to trials in
      patients. 

PMID- 26306769
TI  - Recent investigations into pig antigen and anti-pig antibody expression.
AB  - Genetic engineering of donor pigs to eliminate expression of the dominant
      xenogeneic antigen galactose alpha1,3 galactose (Gal) has created a sea change in
      the immunobiology of xenograft rejection. Antibody mediated xenograft rejection
      of GGTA-1 alpha-galactosyltransferase (GTKO) deficient organs is now directed to
      a combination of non-Gal pig protein and carbohydrate antigens. Glycan analysis
      of GTKO tissues identified no new neo-antigens but detected high levels of N
      acetylneuraminic acid (Neu5Gc) modified glycoproteins and glycolipids. Humans
      produce anti-Neu5Gc antibody and in very limited clinical studies sometimes show
      an induced anti-Neu5Gc antibody response after challenge with pig tissue. The
      pathogenicity of anti-Neu5Gc antibody in xenotransplantation is not clear however
      as non-human transplant models, critical for modelling anti-Gal immunity, do not
      produce anti-Neu5Gc antibody. Antibody induced after xenotransplantation in non
      human primates is directed to an array of pig endothelial cells proteins and to a
      glycan produced by the pig B4GALNT2 gene. We anticipate that immune suppression
      will significantly affect the T-cell dependent and independent specificity of an
      induced antibody response and that donor pigs deficient in synthesis of multiple
      xenogeneic glycans will be important to future studies. 

PMID- 26306772
TI  - Assessment of osteoinduction using a porous hydroxyapatite coating prepared by
      micro-arc oxidation on a new titanium alloy.
AB  - Surface modification and material improvement is now an important way to improve
      the osseointegration between bone and uncemented prothesis. The purpose of this
      study was to investigate the bone ingrowth potential of porous hydroxyapatite
      (HA) coatings prepared by micro-arc oxidation (MAO) on Ti-3Zr-2Sn-3Mo-25Nb, a new
      titanium alloy. HA-coated specimens were implanted in the left proximal femoral
      medullary canal of beagles for 4, 12, and 24 weeks, and uncoated specimens were
      implanted in the right as a control. The surface morphology and phase composition
      were investigated with environmental scanning electron microscopy and X-ray
      diffractometry. The bone ingrowth was assessed by histomorphometry. A pull-out
      test was performed to assess the mechanical performance of the bone-implant
      interface. A porous coating was well prepared on the new titanium alloy by using
      the MAO method. The bone-to-implant contact was significantly higher for the HA
      coated group compared to that in the uncoated group. Mechanical tests showed that
      the HA-coated group had significantly higher maximum force at the bone-implant
      interface compared to the uncoated specimens. MAO is a suitable coating approach
      for this new titanium alloy. The HA coating prepared by this approach can
      significantly promote bone ingrowth and the mechanical performance of the bone
      implant interface.

PMID- 26306771
TI  - Molecular biomarkers in drug-resistant epilepsy: Facts & possibilities.
AB  - Despite great advances in our understanding of the process of epileptogenesis we
      are yet to develop reliable biomarkers that have the potential to accurately
      localize the epileptogenic zone (EZ), and to resolve the issue of heterogeneity
      in epilepsy surgery outcome. Inability to precisely localize the epileptogenic
      foci is one of the reason why more than 30% of these DRE patients are not
      benefited. Molecular and cellular biomarkers in combination with imaging and
      electrical investigations will provide a more specific platform for defining
      epileptogenic zone. Potential molecular biomarkers of epileptogenesis including
      markers of inflammation, synaptic alterations and neurodegeneration may also have
      the potential for localizing EZ. At molecular level components derived from
      epileptogenic tissues, such as metabolites, proteins, mRNAs and miRNAs that are
      significantly altered can serve as biomarkers and can be clubbed with existing
      techniques to preoperatively localize the EZ. Neurosurgeons across the world face
      problems while defining the margins of the epileptogenic tissues to be resected
      during surgery. In this review we discuss molecular biomarkers reported so far in
      the context of epileptogenesis and some of the unexplored markers which may have
      the potential to localize EZ during surgery. We also discuss "Intelligent knife"
      technique that couples electrosurgery and mass spectrometry allowing near-real
      time characterization of human tissue and may prove to be instrumental in
      defining the margins of the epileptogenic zone during surgery.

PMID- 26306773
TI  - Diet-induced modulation of pharmacokinetics of albendazole in Sahiwal cattle.
AB  - The influence of diet type and pre-treatment fasting on the kinetic disposition
      of albendazole was evaluated in Sahiwal heifers following oral and intra-ruminal
      administration of the drug. The anthelmintically active moiety albendazole
      sulphoxide appeared early and was eliminated early in cattle offered green
      fodder, with decreased maximum concentration (C max) and area under concentration
      time curve (AUC) when the drug was administered both through oral and intra
      ruminal routes. Further, the elimination half-life (t 1/2beta) revealed
      significantly increased values for albendazole sulphoxide in cattle administered
      albendazole through the intra-ruminal route. An increased AUC and t 1/2beta is
      reflective of increased bioavailability of albendazole in animals offered dry
      fodder. Increased values (P <  0.05) of C max, time to C max (T max), AUC and t
      1/2beta for albendazole sulphoxide occurred in cattle with a pre-treatment 24-h
      fast, resulting in its increased bioavailability. Extrapolation of data of the
      active metabolite albendazole sulphoxide levels in terms of drug-parasite contact
      revealed increased exposure of parasites to the drug in cattle administered
      albendazole through the intra-ruminal route and with 24-h pre-treatment fasting. 

PMID- 26306774
TI  - Type of fish consumed and thyroid autoimmunity in pregnancy and postpartum.
AB  - Fish consumption or supplementation with omega-3 fatty acids was reported to cure
      and/or prevent autoimmune and nonautoimmune disorders. Serum positivity for
      thyroid autoantibodies is a predictive marker of postpartum thyroiditis and
      postpartum depression. We hypothesized that stable consumption of the omega-3
      rich oily fish was associated with a more favorable profile of serum thyroid
      antibodies throughout pregnancy and early postpartum compared with stable
      consumption of swordfish, a predator that concentrates pollutants. We
      prospectively measured serum thyroglobulin antibodies and thyroperoxidase
      antibodies in pregnancy (first, second trimesters) and postpartum (day 4), in 236
      thyroid disease-free, nonsmoker Caucasian women with stable dietary habits. We
      did not measure thyroid autoantibodies prior to pregnancy. Women were divided
      into groups A (n = 48; swordfish), B (n = 52; oily fish), C (n = 68; swordfish +
      other fish, not necessarily oily fish), and D (n = 68; fish other than swordfish
      and oily fish). Major endpoints were positivity rates and serum concentrations of
      the two autoantibodies. We resorted to previous studies for the estimated content
      of fatty acids and microelements in the consumed fish. Positivity rates and serum
      concentrations of both antibodies were the greatest in group A and the lowest in
      group B (P < 0.001 and P < 0.05 to < 0.001, respectively). Relationship between
      monthly fish consumption and serum concentrations of either antibody was direct
      in group A but inverse in group B. The estimated content of omega-3 fatty acids
      in fish consumed by group B was the greatest (P < 0.001 vs. any other group).
      These data reinforce recommendations that pregnant women should avoid consuming
      swordfish and indicate consumption of oily fish as a favorable alternative.
      Because thyroid autoantibodies are markers of autoimmune-related postpartum
      problems, our data suggest a dietary prophylaxis of such problems.

PMID- 26306775
TI  - Teaching referral skills to medical students.
AB  - BACKGROUND: Referrals are an important and frequent part of a junior doctor's
      work. Difficulty with making successful referrals is also very common. Despite
      this, training in referral skills is not routinely carried out in medical
      schools. RESULTS: We designed and delivered a 1-h interactive lecture to final
      year medical students to teach referral skills. The lecture was delivered on six
      occasions to up to 70 students at each session. 191 students attended and
      provided evaluation. 68% of students had no previous training in referral skills
      and 99% felt that referral skills should be included in the undergraduate
      curriculum. 90% reported that the lecture had improved their understanding of
      referral techniques and 83 and 80% felt that the lecture had improved their
      ability and confidence, respectively. CONCLUSIONS: Referral skills can be
      successfully taught in a large group lecture setting. We recommend that the
      teaching of referral skills is incorporated into all medical schools' curricula.

PMID- 26306776
TI  - Integrating Motivational Interviewing and Traditional Practices to Address
      Alcohol and Drug Use Among Urban American Indian/Alaska Native Youth.
AB  - American Indians/Alaska Natives (AI/AN) exhibit high levels of alcohol and drug
      (AOD) use and problems. Although approximately 70% of AI/ANs reside in urban
      areas, few culturally relevant AOD use programs targeting urban AI/AN youth
      exist. Furthermore, federally-funded studies focused on the integration of
      evidence-based treatments with AI/AN traditional practices are limited. The
      current study addresses a critical gap in the delivery of culturally appropriate
      AOD use programs for urban AI/AN youth, and outlines the development of a
      culturally tailored AOD program for urban AI/AN youth called Motivational
      Interviewing and Culture for Urban Native American Youth (MICUNAY). We conducted
      focus groups among urban AI/AN youth, providers, parents, and elders in two urban
      communities in northern and southern California aimed at 1) identifying
      challenges confronting urban AI/AN youth and 2) obtaining feedback on MICUNAY
      program content. Qualitative data were analyzed using Dedoose, a team-based
      qualitative and mixed methods analysis software platform. Findings highlight
      various challenges, including community stressors (e.g., gangs, violence),
      shortage of resources, cultural identity issues, and a high prevalence of AOD use
      within these urban communities. Regarding MICUNAY, urban AI/AN youth liked the
      collaborative nature of the motivational interviewing (MI) approach, especially
      with regard to eliciting their opinions and expressing their thoughts. Based on
      feedback from the youth, three AI/AN traditional practices (beading, AI/AN
      cooking, and prayer/sage ceremony) were chosen for the workshops. To our
      knowledge, MICUNAY is the first AOD use prevention intervention program for urban
      AI/AN youth that integrates evidence-based treatment with traditional practices.
      This program addresses an important gap in services for this underserved
      population.

PMID- 26306777
TI  - miR-184 is Critical for the motility-related PNS development in Drosophila.

PMID- 26306778
TI  - A stem acrodontan lizard in the Cretaceous of Brazil revises early lizard
      evolution in Gondwana.
AB  - Iguanians are one of the most diverse groups of extant lizards (>1,700 species)
      with acrodontan iguanians dominating in the Old World, and non-acrodontans in the
      New World. A new lizard species presented herein is the first acrodontan from
      South America, indicating acrodontans radiated throughout Gondwana much earlier
      than previously thought, and that some of the first South American lizards were
      more closely related to their counterparts in Africa and Asia than to the modern
      fauna of South America. This suggests both groups of iguanians achieved a
      worldwide distribution before the final breakup of Pangaea. At some point, non
      acrodontans replaced acrodontans and became the only iguanians in the Americas,
      contrary to what happened on most of the Old World. This discovery also expands
      the diversity of Cretaceous lizards in South America, which with recent findings,
      suggests sphenodontians were not the dominant lepidosaurs in that continent as
      previously hypothesized. 

PMID- 26306779
TI  - ArthroBrostrom Lateral Ankle Stabilization Technique: An Anatomic Study.
AB  - BACKGROUND: Arthroscopic ankle lateral ligament repair techniques have recently
      been developed and biomechanically as well as clinically validated. Although
      there has been 1 anatomic study relating suture and anchor proximity to anatomic
      structures, none has evaluated the ArthroBrostrom procedure. PURPOSE: To evaluate
      the proximity of anatomic structures for the ArthroBrostrom lateral ankle
      ligament stabilization technique and to define ideal landmarks and "safe zones"
      for this repair. STUDY DESIGN: Descriptive laboratory study. METHODS: Ten human
      cadaveric ankle specimens (5 matched pairs) were screened for the study. All
      specimens underwent arthroscopic lateral ligament repair according to the
      previously described ArthroBrostrom technique with 2 suture anchors in the
      fibula. Three cadaveric specimens were used to test the protocol, and 7 were
      dissected to determine the proximity of anatomic structures. Several distances
      were measured, including those of different anatomic structures to the suture
      knots, to determine the "safe zones." Measurements were obtained by 2 separate
      observers, and statistical analysis was performed. RESULTS: None of the specimens
      revealed entrapment by either of the suture knots of the critical anatomic
      structures, including the superficial peroneal nerve (SPN), sural nerve, peroneus
      tertius tendon, peroneus brevis tendon, or peroneus longus tendon. The
      internervous safe zone between the intermediate branch of the SPN and sural nerve
      was a mean of 51 mm (range, 39-64 mm). The intertendinous safe zone between the
      peroneus tertius and peroneus brevis was a mean of 43 mm (range, 37-49 mm). On
      average, a 20-mm (range, 8-36 mm) safe distance was maintained from the most
      medial suture to the intermediate branch of the SPN. The amount of inferior
      extensor retinaculum (IER) grasped by either suture knot varied from 0 to 12 mm,
      with 86% of repairs including the retinaculum. CONCLUSION: The results indicate
      that there is a relatively wide internervous and intertendinous safe zone when
      performing the ArthroBrostrom technique for lateral ankle stabilization. While
      none of the critical anatomic structures was entrapped by the suture knots, it
      was evident that the IER was included in a majority of the repairs. This study
      further defines the proximity of adjacent anatomic structures and establishes the
      anatomic safe zones for the ArthroBrostrom lateral ankle stabilization procedure.
      CLINICAL RELEVANCE: By defining this relatively risk-free zone, surgeons who are
      not as experienced with arthroscopic lateral ligament repair techniques may
      approach arthroscopic suture passage with more confidence.

PMID- 26306780
TI  - Platelet-Rich Plasma Attenuates 30-kDa Fibronectin Fragment-Induced Chemokine and
      Matrix Metalloproteinase Expression by Meniscocytes and Articular Chondrocytes.
AB  - BACKGROUND: Proteolytic fragments of fibronectin have catabolic effects on
      cartilage and menisci. Platelet-rich plasma (PRP) is increasingly being used to
      treat a range of joint conditions, but it is unknown whether PRP influences
      fibronectin fragment (FN-f) procatabolic activity. HYPOTHESES: The procatabolic
      activity of FN-f on meniscocytes and articular chondrocytes is attenuated by
      cotreatment with PRP. STUDY DESIGN: Controlled laboratory study. METHODS: Human
      meniscocytes were treated with FN-f (30 kDa) with or without PRP coincubation,
      and gene expression was analyzed by complementary DNA microarray analysis.
      Validation of altered expression of known and novel chemokine and protease genes
      was undertaken by real-time polymerase chain reaction (RT-PCR) in articular
      chondrocytes and meniscocytes. Chemokine release was assayed by enzyme-linked
      immunosorbent assay, and intracellular pathway signaling was evaluated by Western
      immunoblotting. RESULTS: Microarray analysis and RT-PCR showed increased
      expression of matrix metalloproteinase (MMP)1, MMP2, MMP3, MMP9, MMP13,
      interleukin (IL)-6, IL-8 (CXCL8), CCL5, CCL20, and CXCL10 chemokines in
      meniscocytes after treatment with FN-f. Upregulation of these genes was
      significantly attenuated by PRP. Similar results were seen with articular
      chondrocytes, although no changes in MMP2 or MMP9 levels were identified. PRP
      induced suppression of gene expression was associated with activation of Akt and
      p44/p42. CONCLUSION: PRP treatment attenuates the 30-kDa FN-f-induced expression
      of a range of proinflammatory chemokines and MMPs, including IL-8, IL-6, CCL20,
      CCL5, CXCL10, MMP1, MMP3, and MMP13, by both meniscocytes and articular
      chondrocytes. CLINICAL RELEVANCE: These observations provide support for the use
      and further trials of PRP in management of cartilage and meniscal injuries.

PMID- 26306781
TI  - Comprehension of Fish Consumption Guidelines Among Older Male Anglers in
      Wisconsin.
AB  - Although awareness of Wisconsin's fish consumption guidelines is high among older
      male anglers, little is known about comprehension of guideline content, and many
      anglers have levels of contaminants high enough to be associated with adverse
      health outcomes. The Environmental Protection Agency Great Lakes Restoration
      Initiative supported evaluation and revision of Wisconsin's fish consumption
      guideline program, using a web based survey of male Wisconsin anglers over the
      age of 50. A total of 3740 men completed the online survey; the median age of
      respondents was 62 years, and nearly all had lived and fished in Wisconsin for
      over 10 years. Comprehension of guideline content was relatively high, although
      two knowledge gaps were identified, one relating to mercury exposures and fish
      preparation, and the other to polychlorinated biphenyl content of certain fish
      species. The fishing regulations booklet distributed with annual fishing licenses
      and warning signs posted at fishing locations were commonly reported sources of
      guideline information in Wisconsin. Residents of coastal counties and consumers
      of Great Lakes fish were more likely to report guideline knowledge and behavior
      changes reflective of guideline knowledge, when compared to inland residents and
      those not consuming Great Lakes fish, respectively. In general, Wisconsin's
      consumption guidelines do not appear to discourage men from eating the fish they
      catch; rather, the most common behavioral changes included modifying the species
      eaten or the water body source of their meals. Continued efforts to educate
      anglers about the risks and benefits of fish consumption are needed.

PMID- 26306782
TI  - Near-Infrared-Activated Nanocalorifiers in Microcapsules: Vapor Bubble Generation
      for In Vivo Enhanced Cancer Therapy.
AB  - Photothermal therapy based on gold nanostructures has been widely investigated as
      a state-of-the-art noninvasive therapy approach. Because single nanoparticles
      cannot harvest sufficient energy, self-assemblies of small plasmonic particles
      into large aggregates are required for enhanced photothermal performance. Self
      assembled gold nanorods in lipid bilayer-modified microcapsules are shown to
      localize at tumor sites, generate vapor bubbles under near-infrared light
      exposure, and subsequently damage tumor tissues. The polyelectrolyte multilayer
      enables dense packing of gold nanorods during the assembly process, which leads
      to the formation of vapor bubbles around the excited capsules. The resulting
      vapor bubbles achieve a high efficiency of suppressing tumor growth compared to
      single gold nanorods. In vivo experiments demonstrated the ability of soft
      polymer multilayer microcapsules to cross the biological barriers of the body and
      localize at target tissues. 

PMID- 26306783
TI  - MYCN concurrence with SAHA-induced cell death in human neuroblastoma cells.
AB  - BACKGROUND: In the past, the HDAC inhibitor suberoylanilide hydroxamic acid
      (SAHA) has been shown to induce apoptosis in several human tumor types, including
      neuroblastomas. Amplification and over-expression of the MYCN oncogene is a
      diagnostic hallmark and a poor prognostic indicator in high-risk neuroblastomas.
      Here, we studied the relationship between MYCN amplification and over-expression
      and the anti-tumor effect of SAHA to assess whether this drug may serve as a
      treatment option for high-risk neuroblastomas. METHODS: Different human
      neuroblastoma cell lines, over-expressing or not over-expressing MYCN, were used
      in this study. Targeted knockdown and exogenous over-expression of MYCN were
      employed to examine correlations between MYCN expression levels and SAHA
      responses. After various time periods and concentration exposures to the drug,
      cell viability was measured by MTS assay, and variations in MYCN mRNA and protein
      levels were assessed by qPCR and Western blotting, respectively. RESULTS: We
      found that SAHA decreased cell viability in all cell lines tested through
      apoptosis induction, and that SAHA had a stronger effect on cell lines carrying
      an amplified MYCN gene. A decrease in MYCN mRNA and protein levels was observed
      in the SAHA treated cell lines. Subsequent silencing and exogenous over
      expression of MYCN changed the proliferation rate of the cells, but did not have
      any significant impact on the effect of SAHA on the viability of the cells. We
      also found that SAHA blocked the expression of MYCN and, by doing so, reduced the
      effects mediated by this protein. CONCLUSIONS: Our results suggest that SAHA may
      be used as a single-drug treatment option for neuroblastomas with an amplified
      MYCN gene, and as an adjuvant treatment option for all neuroblastomas.

PMID- 26306785
TI  - Ultrasound during Critical Care Simulation: A Randomized Crossover Study.
AB  - OBJECTIVES: We sought to compare two ultrasound simulation interventions used
      during critical care simulation. The primary outcome was trainee and instructor
      preference for either intervention. Secondary outcomes included the
      identification of strengths and weaknesses of each intervention as well as
      overall merits of ultrasound simulation during high-fidelity, critical care
      simulation. The populations of interest included emergency medicine trainees and
      physicians. METHODS: This was a randomized crossover study with two ultrasound
      simulation interventions. 25 trainees and eight emergency physician instructors
      participated in critical-care simulation sessions. Instructors were involved in
      session debriefing and feedback. Pre- and post-intervention responses were
      analyzed for statistically significant differences using t test analyses.
      Qualitative data underwent thematic analysis and triangulation. RESULTS: Both
      trainees and instructors deemed ultrasound simulation valuable by allowing
      trainees to demonstrate knowledge of indications, correct image interpretation,
      and clinical integration (p<0.05). Trainees described increased motivation to
      develop and use ultrasound skills. The edus2 was the preferred intervention, as
      it enabled functional fidelity and the integration of ultrasound into
      resuscitation choreography. Instructors preferred the edus2, as it facilitated
      better assessment of trainees' skills, thus influencing feedback. CONCLUSIONS:
      These findings support the use of ultrasound simulation during critical care
      simulations. The increased functional fidelity associated with edus2 suggests
      that it is the preferred intervention. Further study of the impact on clinical
      performance is warranted.

PMID- 26306784
TI  - Prognostic value of cytokeratin-7 mRNA expression in peripheral whole blood of
      advanced lung adenocarcinoma patients.
AB  - BACKGROUND: The rarity of circulating tumour cells (CTCs) in peripheral blood
      requires the application of sensitive techniques for their detection. The aim of
      our study was to (i) first determine the sensitivity of cytokeratin-7 (KRT7) mRNA
      expression levels for the molecular detection of CTCs using spiked-in lung
      adenocarcinoma (AC)-derived A549 cells and (ii) evaluate the impact of KRT7 mRNA
      expression in peripheral whole blood on the response to treatment and prognosis
      of patients with advanced lung AC who were treated with first-line platinum-based
      chemotherapy. METHODS: A549 cells were micro-manipulated before being spiked into
      whole blood samples obtained from healthy donors. Additionally, whole blood
      samples from 65 lung AC patients were collected in PAXgene blood tubes before the
      start of first-line platinum-based chemotherapy. KRT7 mRNA expression was
      measured using RT-qPCR. RESULTS: Through the spike-in experiment we found that it
      is feasible to detect a single A549 tumour cell in 2.5 ml whole blood and that
      the KRT7 mRNA levels were linearly correlated with the number of spiked-in tumour
      cells with a high reproducibility. In lung AC patients, no significant
      differences in response rate to chemotherapy, progression-free survival or
      overall survival and KRT7 mRNA levels were found. CONCLUSIONS: Our data show that
      KRT7 mRNA expression measured by RT-qPCR serves as a sensitive approach for the
      molecular detection of KRT7-positive CTC-resembling A549 cells in peripheral
      whole blood. The KRT7 mRNA levels measured were not significantly associated with
      the response to chemotherapy or the survival of patients with advanced lung AC.
      Additional studies are required to establish the possible clinical significance
      of KRT7 mRNA expression in whole blood after chemotherapy.

PMID- 26306786
TI  - Apolipoprotein E-epsilon4 deficiency and cognitive function in hepatitis C virus
      infected patients.
AB  - Hepatitis C virus (HCV) causes not only liver damage in certain patients but can
      also lead to neuropsychiatric symptoms. Previous studies have shown that the type
      4 allele of the gene for apolipoprotein E (APOE) is strongly protective against
      HCV-induced damage in liver. In this study, we have investigated the possibility
      that APOE genotype is involved in the action of HCV in brain. One hundred HCV
      infected patients with mild liver disease underwent a neurological examination
      and a comprehensive psychometric testing of attention and memory function. In
      addition, patients completed questionnaires for the assessment of fatigue, health
      related quality of life and mood disturbances. Apolipoprotein E gene genotyping
      was carried out on saliva using buccal swabs. The APOE-epsilon4 allele frequency
      was significantly lower in patients with an impairment of working memory,
      compared to those with a normal working memory test result (P = 0.003). A lower
      APOE-epsilon4 allele frequency was also observed in patients with definitely
      altered attention ability (P = 0.008), but here, the P-value missed the level of
      significance after application of the Bonferroni correction. Our data suggest
      that the APOE-epsilon4 allele is protective against attention deficit and
      especially against poor working memory in HCV-infected subjects with mild liver
      disease. Considering the role of apolipoprotein E in the life cycle of the virus,
      the findings shed interesting new light upon possible pathomechanisms behind the
      development of neuropsychiatric symptoms in hepatitis C infection.

PMID- 26306787
TI  - Prevalence of enterotoxin genes in Staphylococcus aureus colonising food
      handlers: does nasal carriage status matter?
AB  - This study investigated the association between the presence of staphylococcal
      enterotoxin (SE) genes and nasal carriage status, and determined temporal changes
      in the prevalence of these genes in Staphylococcus aureus strains isolated from
      healthy carriers between 2002 and 2011. Three large samples of food handlers
      recruited in 2002, 2003 and 2011 were nasally sampled on two occasions to
      determine S. aureus colonisation status. Those carrying the same spa type on both
      occasions were defined as persistent carriers. Genes for SEs SEA-SEU were
      amplified and associations between carriage status and presence of SE genes were
      investigated. Although 80 % of nasal isolates harboured at least one SE gene over
      the sampling period, persistent carriers were significantly more likely to
      harbour enterotoxigenic S. aureus than transiently colonised subjects [odds ratio
      (OR) 2.52-3.06]. Strains from persistent carriers more commonly harboured sea,
      seb and sem. The prevalence of classical SE genes and sej, sem, sen, seo, seq and
      ses was stable over time, but seh, sel, sep, ser, set and selu increased
      significantly. Increased toxigenicity of isolates from persistent carriers is
      consistent with the elevated antibody levels to classical SEs previously reported
      in persistent carriers, supporting the hypothesis that superantigen production in
      the nasal cavity may enhance colonisation. 

PMID- 26306788
TI  - Elusive Angiostrongylus vasorum infections.
AB  - BACKGROUND: The parasitic nematode Angiostrongylus vasorum causes severe clinical
      signs in dogs. The disease is often challenging because infected animals are
      often presented with clinical signs overlapping those of other diseases. METHODS:
      The present article describes six angiostrongylosis cases (Cases 1-6) that
      represent key examples of how canine angiostrongylosis may be extremely
      confounding. The six animals presented clinical signs compatible with canine
      angiostrongylosis but they were subjected to clinical examinations for other
      diseases (e.g. dirofilariosis or immune-mediated disorders) before achieving a
      correct diagnosis. RESULTS: In Case 1 clinical, radiographic and ultrasound
      examinations' results resembled a lung neoplasia. Case 2 was a dog with a mixed
      infection caused by A. vasorum and Dirofilaria immitis. Case 3 was a critically
      ill dog presented in emergency for an acute onset of dyspnoea caused by lungworm
      infection. The dog died a few hours after presentation despite support and
      etiologic therapy. Case 4 was a dog presented for chronic hemorrhages and
      ecchymoses caused by thrombocytopenia of unknown origin, thought to have an
      inherited, immune-mediated or infective cause. Case 5 was referred for
      neurological signs due to a suspected discospondylitis. Case 6 was erroneously
      diagnosed infected only with D. immitis although the dog was infected only with
      A. vasorum. A timely administration of an anthelmintic (mostly moxidectin) showed
      to be effective in treating the infection in those dogs (i.e. Cases 1,2, 4 and 5)
      that did not suffer with severe lung haemorrhages yet. CONCLUSIONS: Dogs 1-5 were
      referred in two regions of Italy that are considered non-endemic for A. vasorum.
      These findings indicate that veterinarians should include angiostrongylosis in
      the differential diagnosis of cardio-respiratory distress also in non-endemic
      regions and should perform appropriate diagnostics in the presence of compatible
      signs even if the clinical picture is atypical.

PMID- 26306789
TI  - Computational assessment of electron density in metallo-organic nickel pincer
      complexes for formation of P?C bonds.
AB  - Hydrophosphination is an atomically efficient method for introducing new carbon
      phosphorous bonds in organic synthesis. New late-transition metal catalytic
      complexes are proposed to facilitate this process. These nickel-based complexes
      are analyzed using semiempirical (SE), Hartree-Fock (H-F), and density functional
      theory (DFT) models. H-F proves to be ineffective, while the SE approach has
      limited, qualitative use. DFT shows electron density at the metal center suitable
      for catalyzing bond formation in the proposed, reductive hydrophosphination
      mechanism. It also shows that the pincer complexes under investigation are
      relatively insensitive to solvent dielectric constant and to the chemical
      character of the monodentate ligand, both in terms of electron distribution and
      in terms of molecular orbital energies.

PMID- 26306790
TI  - Out-of-School Time and Adolescent Substance Use.
AB  - PURPOSE: High levels of adolescent substance use are linked to lower academic
      achievement, reduced schooling, and delinquency. We assess four types of out-of
      school time (OST) contexts--unsupervised time with peers, sports, organized
      activities, and paid employment--in relation to tobacco, alcohol, and marijuana
      use at the end of high school. Other research has examined these OST contexts in
      isolation, limiting efforts to disentangle potentially confounded relations.
      METHODS: Longitudinal data from the National Institute of Child Health and Human
      Development Study of Early Child Care and Youth Development (N = 766) examined
      associations between different OST contexts during high school and substance use
      at the end of high school. RESULTS: Unsupervised time with peers increased the
      odds of tobacco, alcohol, and marijuana use, whereas sports increased the odds of
      alcohol use and decreased the odds of marijuana use. Paid employment increased
      the odds of tobacco and alcohol use. Unsupervised time with peers predicted
      increased amounts of tobacco, alcohol, and marijuana use, whereas sports
      predicted decreased amounts of tobacco and marijuana use and increased amounts of
      alcohol use at the end of high school. CONCLUSIONS: Although unsupervised time
      with peers, sports, and paid employment were differentially linked to the odds of
      substance use, only unsupervised time with peers and sports were significantly
      associated with the amounts of tobacco, alcohol, and marijuana use at the end of
      high school. These findings underscore the value of considering OST contexts in
      relation to strategies to promote adolescent health. Reducing unsupervised time
      with peers and increasing sports participation may have positive impacts on
      reducing substance use.

PMID- 26306791
TI  - Using Habitat Equivalency Analysis to Assess the Cost Effectiveness of
      Restoration Outcomes in Four Institutional Contexts.
AB  - At the national level, with a fixed amount of resources available for public
      investment in the restoration of biodiversity, it is difficult to prioritize
      alternative restoration projects. One way to do this is to assess the level of
      ecosystem services delivered by these projects and to compare them with their
      costs. The challenge is to derive a common unit of measurement for ecosystem
      services in order to compare projects which are carried out in different
      institutional contexts having different goals (application of environmental laws,
      management of natural reserves, etc.). This paper assesses the use of habitat
      equivalency analysis (HEA) as a tool to evaluate ecosystem services provided by
      restoration projects developed in different institutional contexts. This tool was
      initially developed to quantify the level of ecosystem services required to
      compensate for non-market impacts coming from accidental pollution in the US. In
      this paper, HEA is used to assess the cost effectiveness of several restoration
      projects in relation to different environmental policies, using case studies
      based in France. Four case studies were used: the creation of a market for
      wetlands, public acceptance of a port development project, the rehabilitation of
      marshes to mitigate nitrate loading to the sea, and the restoration of streams in
      a protected area. Our main conclusion is that HEA can provide a simple tool to
      clarify the objectives of restoration projects, to compare the cost and
      effectiveness of these projects, and to carry out trade-offs, without requiring
      significant amounts of human or technical resources. 

PMID- 26306792
TI  - Addressing Climate Change Mitigation and Adaptation Together: A Global Assessment
      of Agriculture and Forestry Projects.
AB  - Adaptation and mitigation share the ultimate purpose of reducing climate change
      impacts. However, they tend to be considered separately in projects and policies
      because of their different objectives and scales. Agriculture and forestry are
      related to both adaptation and mitigation: they contribute to greenhouse gas
      emissions and removals, are vulnerable to climate variations, and form part of
      adaptive strategies for rural livelihoods. We assessed how climate change project
      design documents (PDDs) considered a joint contribution to adaptation and
      mitigation in forestry and agriculture in the tropics, by analyzing 201 PDDs from
      adaptation funds, mitigation instruments, and project standards [e.g., climate
      community and biodiversity (CCB)]. We analyzed whether PDDs established for one
      goal reported an explicit contribution to the other (i.e., whether mitigation
      PDDs contributed to adaptation and vice versa). We also examined whether the
      proposed activities or expected outcomes allowed for potential contributions to
      the two goals. Despite the separation between the two goals in international and
      national institutions, 37% of the PDDs explicitly mentioned a contribution to the
      other objective, although only half of those substantiated it. In addition, most
      adaptation (90%) and all mitigation PDDs could potentially report a contribution
      to at least partially to the other goal. Some adaptation project developers were
      interested in mitigation for the prospect of carbon funding, whereas mitigation
      project developers integrated adaptation to achieve greater long-term
      sustainability or to attain CCB certification. International and national
      institutions can provide incentives for projects to harness synergies and avoid
      trade-offs between adaptation and mitigation.

PMID- 26306793
TI  - Validation of a French-language version of the health education impact
      Questionnaire (heiQ) among chronic disease patients seen in primary care: a cross
      sectional study.
AB  - BACKGROUND: The Health Education Impact Questionnaire (heiQ) allows for the
      evaluation of the effects of education interventions provided to patients with
      chronic diseases. This study describes the process for the cross-cultural
      adaptation and validation of the heiQ into French (heiQ-Fv). METHODS: We
      undertook a systematic translation process followed by a validation study based
      on the secondary analysis of cross-sectional data from a longitudinal study.
      Participants in the validation study were adult patients from primary care
      clinics in Quebec, Canada, with one or more of the following diseases: diabetes,
      asthma, chronic obstructive pulmonary disease, cardiovascular disease; or one or
      more risk factors for these diseases. Main outcomes of the study were the French
      version of the heiQ-Fv and the validation analyses that included internal
      consistency, test-retest reliability, confirmatory factor analysis (CFA) and
      concomitant validity. RESULTS: The validation analysis was conducted on results
      from 332 participants. Cronbach's alphas (internal consistency) for seven domains
      of the heiQ-Fv varied from 0.80 to 0.89; one domain scored 0.69. The test-retest
      analysis (n = 50) yielded intra-class correlation coefficients from 0.66 to 0.86.
      The CFA of the eight heiQ domains with the hypothesis of no correlation between
      the domains yielded a model that did not exhibit acceptable fit values. A model
      with the hypothesis of all domains correlated exhibited acceptable fit values
      (scaled chi-square = 1210.15, degrees of freedom = 712, p < 0.001; CFI = 0.98;
      RMSEA = 0.06; SRMR = 0.065). Results show a moderate correlation (concomitant
      validity) between five domains of the heiQ-Fv and the Self-Efficacy for Managing
      Chronic Diseases. We also found a moderate to strong correlation between the
      Emotional Wellbeing domain of the heiQ and the Kessler Psychological Distress
      Scale (K6) (r = 0.61; 95 % CI: 0.52 -0.69, p < 0.01). CONCLUSIONS: The heiQ was
      translated into French using a rigorous translation process; the French-language
      version showed good psychometric properties. Health professionals and researchers
      in primary care settings may use the heiQ-FV to evaluate the impact of
      educational programs on patients with chronic diseases.

PMID- 26306794
TI  - Management of Hypertensive Patients With Multiple Drug Intolerances: A Single
      Center Experience of a Novel Treatment Algorithm.
AB  - Multiple drug intolerance to antihypertensive medications (MDI-HTN) is an
      overlooked cause of nonadherence. In this study, 55 patients with MDI-HTN were
      managed with a novel treatment algorithm utilizing sequentially initiated
      monotherapies or combinations of maximally tolerated doses of fractional tablet
      doses, liquid formulations, transdermal preparations, and off-label tablet
      medications. A total of 10% of referred patients had MDI-HTN, resulting in
      insufficient pharmacotherapy and baseline office blood pressure (OBP) of 178+/
      24/94+/-15 mm Hg. At baseline, patients were intolerant to 7.6+/-3.6
      antihypertensives; they were receiving 1.4+/-1.1 medications. After 6 months on
      the novel MDI-HTN treatment algorithm, both OBP and home blood pressure (HBP)
      were significantly reduced, with patients receiving 2.0+/-1.2 medications. At 12
      months, OBP was reduced from baseline by 17+/-5/9+/-3 mm Hg (P<.01, P<.05) and
      HBP was reduced by 11+/-5/12+/-3 mm Hg (P<.01 for both) while patients were
      receiving 1.9+/-1.1 medications. Application of a stratified medicine approach
      allowed patients to tolerate increased numbers of medications and achieved
      significant long-term lowering of blood pressure. 

PMID- 26306796
TI  - Family Functioning and Parental Bonding During Childhood in Adults Diagnosed With
      ADHD.
AB  - OBJECTIVE: This work assesses family functioning, parental bonding, and the
      relationship between the two in adults diagnosed with ADHD. METHOD: The study
      used a retrospective, ex post facto design and consisted of 100 adult
      participants, who were distributed into two groups: with and without diagnosis of
      ADHD. Two family assessment instruments were applied: the Family Adaptability and
      Cohesion Evaluation Scale short spanish version (FACES-20esp)) and the Parental
      Bonding Instrument (PBI). The diagnosis of ADHD was done by using a
      semistructured interview for Diagnostic and Statistical Manual of Mental
      Disorders (4th ed.; DSM-IV) criteria (Conners' Adult ADHD Diagnostic Interview
      for DSM-IV [CAADID]). RESULTS: The results showed that higher rigidity and lower
      emotional connection were significantly associated with ADHD family functioning.
      Regarding parental bonding, the results showed significant differences only in
      the care dimension, with the ADHD group reporting lower care than the control
      group. CONCLUSION: The results suggest that ADHD families present dysfunctional
      family functioning with a rigid, separated typology, and parental bonding based
      on control without affection.

PMID- 26306797
TI  - Food Sensing: Aptamer-Based Trapping of Bacillus cereus Spores with Specific
      Detection via Real Time PCR in Milk.
AB  - Aerobic spores pose serious problems for both food product manufacturers and
      consumers. Milk is particularly at risk and thus an important issue of preventive
      consumer protection and quality assurance. The spore-former Bacillus cereus is a
      food poisoning Gram-positive pathogen which mainly produces two different types
      of toxins, the diarrhea inducing and the emetic toxins. Reliable and rapid
      analytical assays for the detection of B. cereus spores are required, which could
      be achieved by combining in vitro generated aptamers with highly specific
      molecular biological techniques. For the development of routine bioanalytical
      approaches, already existing aptamers with high affinity to B. cereus spores have
      been characterized by surface plasmon resonance (SPR) spectroscopy and
      fluorescence microscopy in terms of their dissociation constants and selectivity.
      Dissociation constants in the low nanomolar range (from 5.2 to 52.4 nM) were
      determined. Subsequently, the characterized aptamers were utilized for the
      establishment and validation of an aptamer-based trapping technique in both milk
      simulating buffer and milk with fat contents between 0.3 and 3.5%. Thereby,
      enrichment factors of up to 6-fold could be achieved. It could be observed that
      trapping protocol and characterized aptamers were fully adaptable to the
      application in milk. Due to the fact that aptamer selectivity is limited, a
      highly specific real time PCR assay was utilized following trapping to gain a
      higher degree of selectivity. 

PMID- 26306795
TI  - Transcriptomic changes of Legionella pneumophila in water.
AB  - BACKGROUND: Legionella pneumophila (Lp) is a water-borne opportunistic pathogen.
      In water, Lp can survive for an extended period of time until it encounters a
      permissive host. Therefore, identifying genes that are required for survival in
      water may help develop strategies to prevent Legionella outbreaks. RESULTS: We
      compared the global transcriptomic response of Lp grown in a rich medium to that
      of Lp exposed to an artificial freshwater medium (Fraquil) for 2, 6 and 24 hours.
      We uncovered successive changes in gene expression required for the successful
      adaptation to a nutrient-limited water environment. The repression of major
      pathways involved in cell division, transcription and translation, suggests that
      Lp enters a quiescent state in water. The induction of flagella associated genes
      (flg, fli and mot), enhanced-entry genes (enh) and some Icm/Dot effector genes
      suggests that Lp is primed to invade a suitable host in response to water
      exposure. Moreover, many genes involved in resistance to antibiotic and oxidative
      stress were induced, suggesting that Lp may be more tolerant to these stresses in
      water. Indeed, Lp exposed to water is more resistant to erythromycin, gentamycin
      and kanamycin than Lp cultured in rich medium. In addition, the bdhA gene,
      involved in the degradation pathway of the intracellular energy storage compound
      polyhydroxybutyrate, is also highly expressed in water. Further characterization
      show that expression of bdhA during short-term water exposure is dependent upon
      RpoS, which is required for the survival of Lp in water. Deletion of bdhA reduces
      the survival of Lp in water at 37  degrees C. CONCLUSIONS: The increase of
      antibiotic resistance and the importance of bdhA to the survival of Lp in water
      seem consistent with the observed induction of these genes when Lp is exposed to
      water. Other genes that are highly induced upon exposure to water could also be
      necessary for Lp to maintain viability in the water environment.

PMID- 26306798
TI  - The re-enactment of childhood sexual abuse in maternity care: a qualitative
      study.
AB  - BACKGROUND: The process of pregnancy and birth are profound events that can be
      particularly challenging for women with a history of childhood sexual abuse. The
      silence that surrounds childhood sexual abuse means that few women disclose it
      and those caring for them will often not be aware of their history. It is known
      from anecdotal accounts that distressing memories may be triggered by childbirth
      and maternity care but research data on the subject are rare. This paper explores
      aspects of a study on the maternity care experiences of women who were sexually
      abused in childhood that demonstrate ways that maternity care can be reminiscent
      of abuse. Its purpose is to inform those providing care for these women. METHODS:
      The experiences of women were explored through in-depth interviews in this
      feminist narrative study. The Voice-Centred Relational Method and thematic
      analysis were employed to examine interview data. RESULTS: Women sometimes
      experienced re-enactment of abuse through intimate procedures but these were not
      necessarily problematic in themselves. How they were conducted was important.
      Women also experienced re-enactment of abuse through pain, loss of control,
      encounters with strangers and unexpected triggers. Many of these experiences were
      specific to the woman, often unpredictable and not necessarily avoidable.
      Maternity care was reminiscent of abuse for women irrespective of whether they
      had disclosed to midwives and was not necessarily prevented by sensitive care.
      'Re-enactment of abuse' occurred both as a result of events that involved the
      crossing of a woman's body boundaries and more subjective internal factors that
      related to her sense of agency. CONCLUSIONS: As staff may not know of a woman's
      history, they must be alert to unspoken messages and employ 'universal
      precautions' to mitigate hidden trauma. Demonstrating respect and enabling women
      to retain control is crucial. Getting to know women is important in the building
      of trusting relationships that will facilitate the delivery of sensitive care and
      enable women to feel safe so that the re-enactment of abuse in maternity care is
      minimised.

PMID- 26306799
TI  - Prevalence of coenurosis in sheep and goats at three slaughter slabs in
      Ngorongoro District, Tanzania.
AB  - Prevalence of Coenurus cerebralis prevalence was assessed in sheep and goats at
      three slaughter slabs in Ngorongoro district, Tanzania. Predisposing factors were
      also determined by using a structured questionnaire. Between January 2013 and
      April 2013, a total of 180 heads (90 sheep and 90 goats) were collected and
      examined for the presences of C. cerebralis cysts. Out of 180 heads examined, 80
      were found to be infected with C. cerebralis. Lack of knowledge in the community
      on how coenurosis occurs, free access of dogs to the carcasses/offal of small
      ruminants and inadequate animal health services for dogs especially worm control
      were major factors which contribute to persistence of coenurosis. This study, in
      Ngorongoro district, reports for the first time the occurrence and prevalence of
      coenurosis in slaughtered sheep and goats due to Taenia multiceps metacestode (C.
      cerebralis). It is recommended that more studies are undertaken in order to pave
      the way for developing preliminary coenurosis control guidelines and for sign
      posting the direction for future research. 

PMID- 26306800
TI  - A novel olfactory pathway is essential for fast and efficient blood-feeding in
      mosquitoes.
AB  - In mosquitoes, precise and efficient finding of a host animal is crucial for
      survival. One of the poorly understood aspects of mosquito blood-feeding behavior
      is how these insects target an optimal site in order to penetrate the skin and
      blood vessels without alerting the host animal. Here we provide new findings that
      a piercing structure of the mouthpart of the mosquitoes, the stylet, is an
      essential apparatus for the stage in blood feeding. Indeed, the stylet possesses
      a number of sensory hairs located at the tip of the stylet. These hairs house
      olfactory receptor neurons that express two conventional olfactory receptors of
      Aedes aegypti (AaOrs), AaOr8 and AaOr49, together with the odorant co-receptor
      (AaOrco). In vivo calcium imaging using transfected cell lines demonstrated that
      AaOr8 and AaOr49 were activated by volatile compounds present in blood.
      Inhibition of gene expression of these AaOrs delayed blood feeding behaviors of
      the mosquito. Taken together, we identified olfactory receptor neurons in the
      stylet involved in mosquito blood feeding behaviors, which in turn indicates that
      olfactory perception in the stylet is necessary and sufficient for mosquitoes to
      find host blood in order to rapidly acquire blood meals from a host animal. 

PMID- 26306802
TI  - Patient-reported outcomes in the Swedish National Quality Registers.
AB  - Patient-reported outcomes (PROs) are important in the healthcare system to gain
      understanding of patients' views on the effects of a treatment. There is an
      abundance of available patient-reported outcome measures (PROMs), both disease
      specific and generic. In the Swedish healthcare system, the national quality
      registers are obliged to incorporate PROs for certification at a high level. A
      review of the latest annual applications for funding (n = 108) shows that at
      present, 93 national quality registers include some form of PROM or patient
      reported experience measure (PREM). Half of the registers include some type of
      generic measure, more than half include disease/symptom-specific measures, and
      around 40% include PREMs. Several different measures and combinations of measures
      are used, the most common of which are the EQ-5D, followed by the SF-36/RAND-36.
      About one-fifth of the registers report examples of how patient-reported data are
      used for local quality improvement. These examples include enhancing shared
      decision-making in clinical encounters (most common), as a basis for care plans,
      clinical decision aids and treatment guidelines, to improve the precision of
      indications for surgery (patient and healthcare professional assessments may
      differ), to monitor complications after the patient has left hospital and to
      improve patient information. In addition, funding applications reveal that most
      registers plan to extend their array of PROMs and PREMs in future, and to
      increase their use of patient-reported data as a basis for quality improvement. 

PMID- 26306801
TI  - Distinct clinical and neuropathological features of G51D SNCA mutation cases
      compared with SNCA duplication and H50Q mutation.
AB  - BACKGROUND: We and others have described the neurodegenerative disorder caused by
      G51D SNCA mutation which shares characteristics of Parkinson's disease (PD) and
      multiple system atrophy (MSA). The objective of this investigation was to extend
      the description of the clinical and neuropathological hallmarks of G51D mutant
      SNCA-associated disease by the study of two additional cases from a further G51D
      SNCA kindred and to compare the features of this group with a SNCA duplication
      case and a H50Q SNCA mutation case. RESULTS: All three G51D patients were
      clinically characterised by parkinsonism, dementia, visual hallucinations,
      autonomic dysfunction and pyramidal signs with variable age at disease onset and
      levodopa response. The H50Q SNCA mutation case had a clinical picture that
      mimicked late-onset idiopathic PD with a good and sustained levodopa response.
      The SNCA duplication case presented with a clinical phenotype of frontotemporal
      dementia with marked behavioural changes, pyramidal signs, postural hypotension
      and transiently levodopa responsive parkinsonism. Detailed post-mortem
      neuropathological analysis was performed in all cases. All three G51D cases had
      abundant alpha-synuclein pathology with characteristics of both PD and MSA. These
      included widespread cortical and subcortical neuronal alpha-synuclein inclusions
      together with small numbers of inclusions resembling glial cytoplasmic inclusions
      (GCIs) in oligodendrocytes. In contrast the H50Q and SNCA duplication cases, had
      alpha-synuclein pathology resembling idiopathic PD without GCIs. Phosphorylated
      alpha-synuclein was present in all inclusions types in G51D cases but was more
      restricted in SNCA duplication and H50Q mutation. Inclusions were also
      immunoreactive for the 5G4 antibody indicating their highly aggregated and likely
      fibrillar state. CONCLUSIONS: Our characterisation of the clinical and
      neuropathological features of the present small series of G51D SNCA mutation
      cases should aid the recognition of this clinico-pathological entity. The
      neuropathological features of these cases consistently share characteristics of
      PD and MSA and are distinct from PD patients carrying the H50Q or SNCA
      duplication.

PMID- 26306803
TI  - Effect exerted by Teriparatide upon Repair Function of beta-tricalcium phosphate
      to ovariectomised rat's femoral metaphysis defect caused by osteoporosis.
AB  - In this study, we tested the effect of Teriparatide (PTH) in combination with
      beta-tricalcium phosphate (beta-TCP) as a bone void filler in an ovariectomised
      rat distal femoral metaphysis model.beta-TCP is a completely resorbable synthetic
      calcium phosphate and the Teriparatide is a drug that can promote bone formation
      in the condition of osteoporosis. A critical size defect of 3mm in diameter, a
      through-hole bone defect, was drilled into each distal femur of the
      ovariectomised rats. The hole was filled with beta-TCP and the rat was injected
      PTH Teriparatide (30MUg/kg) in peritoneum 5 times per week. After 4and 8 weeks
      the animals were killed and the degree of bone healing analysed. In total, 60
      animals were investigated. When the beta-TCP and PTH were used, histological,
      biochemistry and histomor-phometric evaluations revealed significantly better
      bone healing in terms of quantity and quality of the newly formed bone. The
      Ovariectomised rats which suffer from femur metaphysis defect are cured by
      embedding beta-tricalcuim phosphate and intermittently cured by parathyroid
      hormone (PTH). 

PMID- 26306805
TI  - Nonsurgical Management of Early-onset Scoliosis.
AB  - Early-onset scoliosis is potentially fatal if left untreated. Although surgical
      management with growing instrumentation may be necessary, this is not a panacea
      and is associated with high complication rates. Recent evidence has demonstrated
      that nonsurgical treatment can be an effective early management strategy in
      delaying or even precluding the need for surgery, especially surgery with growing
      instrumentation. The goal of both nonsurgical and surgical management is to
      control or correct the spinal curve to allow appropriate pulmonary development
      while delaying definitive fusion until an appropriate skeletal age. Although more
      commonly used to delay surgery, serial cast correction using the Cotrel and Morel
      elongation-derotation-flexion technique may result in complete correction in
      patients with infantile idiopathic scoliosis and smaller curve magnitudes. 

PMID- 26306804
TI  - Influences of large sets of environmental exposures on immune responses in
      healthy adult men.
AB  - Environmental factors have long been known to influence immune responses. In
      particular, clinical studies about the association between migration and
      increased risk of atopy/asthma have provided important information on the role of
      migration associated large sets of environmental exposures in the development of
      allergic diseases. However, investigations about environmental effects on immune
      responses are mostly limited in candidate environmental exposures, such as air
      pollution. The influences of large sets of environmental exposures on immune
      responses are still largely unknown. A simulated 520-d Mars mission provided an
      opportunity to investigate this topic. Six healthy males lived in a closed
      habitat simulating a spacecraft for 520 days. When they exited their "spacecraft"
      after the mission, the scenario was similar to that of migration, involving
      exposure to a new set of environmental pollutants and allergens. We measured
      multiple immune parameters with blood samples at chosen time points after the
      mission. At the early adaptation stage, highly enhanced cytokine responses were
      observed upon ex vivo antigen stimulations. For cell population frequencies, we
      found the subjects displayed increased neutrophils. These results may presumably
      represent the immune changes occurred in healthy humans when migrating,
      indicating that large sets of environmental exposures may trigger aberrant immune
      activity. 

PMID- 26306806
TI  - Granulomatous Vertebral Osteomyelitis: An Update.
AB  - A granulomatous infection of the spine is characterized by an infectious process
      within the spinal elements that results in the formation of a granuloma, an
      organized collection of transformed macrophages (ie, epithelioid cells), matrix,
      and other inflammatory cells. Causative organisms include various bacteria,
      fungi, or other parasites; however, the most frequently encountered causative
      organism is Mycobacterium tuberculosis (ie, Pott disease). The onset of these
      infections is often insidious, frequently leading to a delay in diagnosis. Left
      untreated, this disease process may lead to a compromise in the structural
      integrity of the spine and subsequent spinal deformity that may eventually result
      in compression of neural elements. Successful treatment of a granulomatous
      infection requires timely diagnosis, prompt medical management, and potential
      surgical intervention directed at the decompression of neural elements and the
      correction of spinal malalignment. Of granulomatous infections, tuberculous
      infections are the most thoroughly understood and serve as the standard to which
      other less commonly reported organisms are compared. 

PMID- 26306807
TI  - Double Crush Syndrome.
AB  - Double crush syndrome is a distinct compression at two or more locations along
      the course of a peripheral nerve that can coexist and synergistically increase
      symptom intensity. In addition, dissatisfaction after treatment at one site may
      be the result of persistent pathology at another site along a peripheral nerve.
      Double crush syndrome is a controversial diagnosis; some scientists and surgeons
      believe it is an illness construction that may do more harm than good because it
      emphasizes an objective pathophysiologic explanation for unexplained symptoms,
      disability, and dissatisfaction that may be more psychosocially mediated.
      However, peripheral neuropathy may coexist with compressive neuropathy and
      contribute to suboptimal outcomes following nerve decompression. To better manage
      patients' expectations, treating practitioners should be aware of the possibility
      of concomitant cervical radiculopathy and carpal tunnel syndrome, as well as the
      presence of underlying systemic neuropathy. 

PMID- 26306808
TI  - Urinary incontinence: prevalence, pattern, and opportunistic screening in Ile
      Ife, Nigeria.
AB  - INTRODUCTION AND HYPOTHESIS: Urinary incontinence is a source of health-related
      poor quality of life. It is, however, rarely disclosed, except when specifically
      enquired about by the healthcare provider. This study determined the prevalence
      of urinary incontinence and opportunistic screening for it in women attending a
      general outpatient clinic. METHODS: A total of 1,250 consenting women attending a
      general outpatient clinic in Ile-Ife, a semi-urban town in Southwest Nigeria,
      were recruited into this cross-sectional study. Confidential post-consultation
      interviews were performed in each patient to determine whether they had been
      asked about urinary incontinence and whether they felt that they ought to have
      been asked. The Questionnaire for Urinary Incontinence Diagnosis (QUID) was
      administered to determine the prevalence and pattern of urinary incontinence.
      Results were expressed as proportions and compared using the Chi-squared test.
      RESULTS: The subjects' ages ranged from 20 to 100 years (mean = 46.8 +/- 17.7
      years). Sixty-five women had urinary incontinence (prevalence = 5.2 %). QUID
      classified 30 (2.4 %), 23 (1.8 %), and 12 (1.0 %) of them as having urge, stress,
      and mixed incontinence respectively. None of them self-reported incontinence to
      their physicians. Only 9 incontinent (13.8 %) and 44 continent women (3.7 %) had
      opportunistic screening (p < 0.001). Fifty of the incontinent women (76.9 %) felt
      that their physician ought to have asked them about it. Forty-eight of them (73.8
      %) did not consider incontinence a sufficient reason for presentation in
      hospital, but the majority (90.7 %) desired treatment. CONCLUSION: Urinary
      incontinence was occasionally present, but usually undisclosed by women attending
      the general outpatient clinic, unless when specifically asked by their
      physicians. Opportunistic screening is therefore recommended in this setting.

PMID- 26306809
TI  - Inhibition of human GLUT1 and GLUT5 by plant carbohydrate products; insights into
      transport specificity.
AB  - Glucose transporters GLUT1 (transports glucose) and GLUT5 (transports fructose),
      in addition to their functions in normal metabolism, have been implicated in
      several diseases including cancer and diabetes. While GLUT1 has several
      inhibitors, none have been described for GLUT5. By transport activity assays we
      found two plant products, rubusoside (from Rubus suavissimus) and astragalin-6
      glucoside (a glycosylated derivative of astragalin, from Phytolacca americana)
      that inhibited human GLUT5. These plants are utilized in traditional medicine: R.
      suavissimus for weight loss and P. americana for cancer treatment, but the
      molecular interactions of these products are unknown. Rubusoside also inhibited
      human GLUT1, but astragalin-6-glucoside did not. In silico analysis of
      rubusoside:protein interactions pinpointed a major difference in substrate cavity
      between these transporters, a residue that is a tryptophan in GLUT1 but an
      alanine in GLUT5. Investigation of mutant proteins supported the importance of
      this position in ligand specificity. GLUT1W388A became susceptible to inhibition
      by astragalin-6-glucoside and resistant to rubusoside. GLUT5A396W transported
      fructose and also glucose, and maintained inhibition by rubusoside and astragalin
      6-glucoside. Astragalin-6-glucoside can serve as a starting point in the design
      of specific inhibitors for GLUT5. The application of these studies to
      understanding glucose transporters and their interaction with substrates and
      ligands is discussed. 

PMID- 26306810
TI  - Reliability of Visual and Somatosensory Feedback in Skilled Movement: The Role of
      the Cerebellum.
AB  - The integration of vision and somatosensation is required to allow for accurate
      motor behavior. While both sensory systems contribute to an understanding of the
      state of the body through continuous updating and estimation, how the brain
      processes unreliable sensory information remains to be fully understood in the
      context of complex action. Using functional brain imaging, we sought to
      understand the role of the cerebellum in weighting visual and somatosensory
      feedback by selectively reducing the reliability of each sense individually
      during a tool use task. We broadly hypothesized upregulated activation of the
      sensorimotor and cerebellar areas during movement with reduced visual
      reliability, and upregulated activation of occipital brain areas during movement
      with reduced somatosensory reliability. As specifically compared to reduced
      somatosensory reliability, we expected greater activations of ipsilateral
      sensorimotor cerebellum for intact visual and somatosensory reliability. Further,
      we expected that ipsilateral posterior cognitive cerebellum would be affected
      with reduced visual reliability. We observed that reduced visual reliability
      results in a trend towards the relative consolidation of sensorimotor activation
      and an expansion of cerebellar activation. In contrast, reduced somatosensory
      reliability was characterized by the absence of cerebellar activations and a
      trend towards the increase of right frontal, left parietofrontal activation, and
      temporo-occipital areas. Our findings highlight the role of the cerebellum for
      specific aspects of skillful motor performance. This has relevance to
      understanding basic aspects of brain functions underlying sensorimotor
      integration, and provides a greater understanding of cerebellar function in tool
      use motor control. 

PMID- 26306812
TI  - Non-uniform Solute Segregation at Semi-Coherent Metal/Oxide Interfaces.
AB  - The properties and performance of metal/oxide nanocomposites are governed by the
      structure and chemistry of the metal/oxide interfaces. Here we report an
      integrated theoretical and experimental study examining the role of interfacial
      structure, particularly misfit dislocations, on solute segregation at a
      metal/oxide interface. We find that the local oxygen environment, which varies
      significantly between the misfit dislocations and the coherent terraces, dictates
      the segregation tendency of solutes to the interface. Depending on the nature of
      the solute and local oxygen content, segregation to misfit dislocations can
      change from attraction to repulsion, revealing the complex interplay between
      chemistry and structure at metal/oxide interfaces. These findings indicate that
      the solute chemistry at misfit dislocations is controlled by the dislocation
      density and oxygen content. Fundamental thermodynamic concepts - the Hume-Rothery
      rules and the Ellingham diagram - qualitatively predict the segregation behavior
      of solutes to such interfaces, providing design rules for novel interfacial
      chemistries.

PMID- 26306811
TI  - Hsa-miR-146a-5p modulates androgen-independent prostate cancer cells apoptosis by
      targeting ROCK1.
AB  - BACKGROUND: MicroRNAs (miRNAs) have been demonstrated playing important roles in
      the procession of prostate cancer cells transformation from androgen-dependence
      to androgen-independence. METHODS: We conducted the miRNA microarray and realtime
      PCR analyses in both androgen-dependent (ADPC) and androgen-independent prostate
      cancer (AIPC) tissues. We also explored the role of hsa-miR-146a-5p (miR-146a) in
      MSKCC prostate cancer clinical database. Moreover, the impact of miR-146a on
      prostate cancer cells apoptosis were detected by Hoechst staining and
      fluorescence-activated cell sorter (FACS). Its target is predicted by DIANA LAB
      online database and the result was assumed by western blotting and luciferase
      assay. RESULTS: We demonstrated that miR-146a was down-regulated in AIPC tissues
      and cell lines compared to that in the ADPC tissues. In MSKCC data re-analyses,
      we found that miR-146a was underexpressed in metastatic prostate cancer tissues
      and those with Gleason score >8, moreover, low level of miR-146a represented a
      high biochemical relapse rate after radical prostatectomy. In the functional
      analyses, we transfected miR-146a mimics into CPRC cell lines and found miR-146a
      induced cells apoptosis. In mechanic analyses, we found that miR-146a inhibited
      the basal level of Rho-associated, coiled-coil containing protein kinase 1
      (ROCK1) expression by targeting its 3'UTR and an inverse correlation of
      expression between miR-146a and ROCK1 was observed. Moreover, caspase 3 activity
      was stimulated by miR-146a overexpression. CONCLUSION: miR-146a has a critical
      role in the process of AIPC prostate cancer cells apoptosis through regulation of
      ROCK/Caspase 3 pathway. Targeting this pathway may be a promising therapeutic
      strategy for future personalized anti-cancer treatment.

PMID- 26306813
TI  - Microsurgeons do better--tactile training might prevent the age-dependent decline
      of the sensibility of the hand.
AB  - Recent data demonstrate that the normal sensibility of the hand seems to be age
      dependent with the best values in the third decade and a consecutive
      deterioration afterwards. However, it is not clear if long-term tactile training
      might prevent this age-dependent decline. We evaluated sensibility of the hand in
      125 surgeons aged between 26 and 75 years who perform microsurgical operations,
      thereby undergoing regular tactile training. We examined sensibility of the
      radial digital nerve of the index finger (N3) and the ulnar digital nerve of the
      small finger (N10) using static and moving two-point discrimination (2PD) tests
      and compared the results to 154 age-matched individuals without specific long
      term tactile training. We found significantly lower static and moving 2PD values
      for the sixth, seventh, and eighth decade of life in the microsurgery group
      compared to the control group (p < 0.05). This study demonstrates that long-term
      tactile training might prevent the known age-dependent decline of the sensibility
      of the hand. 

PMID- 26306814
TI  - Zincmethylphyrins and coproporphyrins, novel growth factors released by
      Sphingopyxis sp., enable laboratory cultivation of previously uncultured
      Leucobacter sp. through interspecies mutualism.
AB  - We have identified coproporphyrins including structurally new zincmethylphyrins I
      and III as growth factors A-F for the previously uncultured bacterial strain,
      Leucobacter sp. ASN212, from a supernatant of 210 l of Sphingopyxis sp. GF9
      culture. Growth factors A-F induced significant growth of strain ASN212 at the
      concentrations of picomolar to nanomolar which would otherwise be unculturable in
      liquid medium or on agar plate. More interestingly, we found that the growth
      factors functioned as self-toxic compounds for the growth-factor producing strain
      GF9 at the picomolar to nanomolar levels. As a variety of bacteria could
      potentially produce coproporphyrins, our findings suggest that these compounds
      function as a novel class of signal molecules across a boundary at phylum level
      in the complex bacterial communities. 

PMID- 26306815
TI  - Verrulactones D and E with unprecedented skeletons, new inhibitors of
      Staphylococcus aureus enoyl-ACP reductase, from Penicillium verruculosum F375.

PMID- 26306816
TI  - Isolation and structure elucidation of new phthalide and phthalane derivatives,
      isolated as antimicrobial agents from Emericella sp. IFM57991.
AB  - Three new phthalide derivatives, emefuranones A1, A2 and B (1-3); six new
      phthalane derivatives, emefuran A, B1, B2, C1, C2 and D (4-9); three new
      farnesylated phthalide derivatives, farnesylemefuranones A-C (10-12); xylarinol C
      (13); and emericelloxide (14), along with four known compounds (dustanin,
      sorbicillin, aspergillodiol and xylarinol A), were isolated from the culture
      extracts of Emericella sp. IFM57991. Structures of 1-14 were elucidated on the
      basis of spectroscopic analysis and chemical evidence. Compounds 4-7 and 13
      showed moderate antibacterial activities against Bacillus subtilis. 

PMID- 26306817
TI  - Structure and activity relationships of the anti-Mycobacterium antibiotics
      resorcinomycin and pheganomycin.

PMID- 26306818
TI  - Effect of a Limited Iodine Diet on Iodine Uptake by Thyroid Glands in
      Hyperthyroid Cats.
AB  - BACKGROUND: The effect of feeding a limited iodine diet on radioactive iodine
      uptake in the thyroid glands of hyperthyroid cats is unknown. OBJECTIVES: To
      determine how feeding limited dietary iodine affects radioactive iodine uptake by
      the thyroid glands of hyperthyroid cats. ANIMALS: Eight geriatric cats with
      spontaneous hyperthyroidism. METHODS: Prospective study of eight client owned
      hyperthyroid cats fed a commercially available iodine limited diet for 6 months.
      Clinical signs were evaluated and TT4 and fT4 were measured during consumption of
      the diet. Uptake of (123)I was determined before and 8-16 weeks after exclusive
      consumption of the diet. RESULTS: Clinical signs of hyperthyroidism resolved in
      all cats, but there was no significant increase in body weight. TT4 and fT4
      decreased into the reference range by 8-16 weeks in all cats. Mean TT4 before
      consumption of the diet was 9.7 MUg/dL (SD 5.2) and after consumption of the diet
      was 3.1 MUg/dL (SD 0.9). Scintigraphy revealed unilateral uptake of isotope in 5
      cats and bilateral uptake in 3 cats. Mean percentage uptake of (123)I by the
      thyroid gland at 8 hours after isotope administration was 16.2 (SD 11.8) before
      diet consumption and 34.6 (SD 11.7) 8-16 weeks after exclusive consumption of the
      diet. The percentage increase was variable between cats (38-639%). CONCLUSIONS
      AND CLINICAL IMPORTANCE: Limited iodine diets increase iodine uptake in the
      autonomous thyroid glands of hyperthyroid cats. Further studies are necessary to
      determine if consumption of a limited iodine diet changes sensitivity of the
      thyroid gland to (131)I treatment.

PMID- 26306819
TI  - Practical guidance for dosing and switching from paliperidone palmitate 1 monthly
      to 3 monthly formulation in schizophrenia.
AB  - OBJECTIVE: This commentary summarizes recommended dosing strategies for a
      recently developed 3 monthly long-acting injectable 1 (LAI) formulation of
      paliperidone palmitate (PP3M) for the treatment of schizophrenia in adults.
      METHODS: Recommendations for different dosing scenarios are based on the
      pharmacokinetic, efficacy and safety outcomes from phase 1 and phase 3 studies,
      population pharmacokinetic models, and model based simulations. RESULTS:
      Switching to PP3M treatment is recommended only in patients previously treated
      with once monthly paliperidone palmitate LAI (PP1M) for at least 4 months. The
      first injection of PP3M (175 to 525 mg equivalent [eq.]) should be given at the
      time of next scheduled injection of PP1M as a 3.5-fold multiple of the last PP1M
      dose (50-150 mg eq.), with a dosing window of +/- 1 week. Following that first
      injection of PP3M, once-every-three-months maintenance injections with PP3M are
      recommended, with a dosing window of +/- 2 weeks. The doses of PP3M can be
      administered in either deltoid (>= 90 kg: 1.5 inch 22 G needle; <90 kg: 1.0 inch
      22 G needle) or gluteal muscles (1.5 inch 22 G needle regardless of weight). In
      patients with mild renal impairment (creatinine clearance: 50-80 mL/min), a 25%
      dose reduction in PP1M and subsequent switching to a corresponding 3.5-dose
      multiple of PP3M (but not exceeding 350 mg eq.) is recommended. Appropriate
      dosing is recommended in elderly patients with diminished renal function not
      exceeding mild renal impairment. Similarly to PP1M, PP3M is not recommended in
      patients with moderate/severe renal impairment. Like PP1M, no dosage adjustment
      is required in patients with mild or moderate hepatic impairment or elderly
      patients with normal renal function. CONCLUSIONS: These data provide clinical
      guidelines for the optimum use of PP3M in patients with schizophrenia previously
      treated with PP1M for at least 4 months. REGISTRATION: ClinicalTrials.gov
      identifier: NCT01559272 and NCT01529515.

PMID- 26306820
TI  - Prognosis and course of work-participation in patients with chronic non-specific
      low back pain: a 12-month follow-up cohort study.
AB  - OBJECTIVE: To investigate the clinical course of, and prognostic factors for,
      work-participation in patients with chronic non-specific low back pain. METHODS:
      A total of 1,608 patients with chronic non-specific low back pain received a
      multidisciplinary therapy and were evaluated at baseline and 2-, 5- and 12-month
      follow-ups. Recovery was defined as absolute recovery if the patient worked 90%
      of his contract hours at follow-up. Potential factors were identified using
      multivariable logistic regression analysis. RESULTS: Patients reported a mean
      increase in work-participation from 38% at baseline to 82% after 12 months.
      Prognostic factors for >= 90% work-participation at 5 months were being married
      (odds ratio (OR) 1.72 (95% confidence interval (95% CI) 1.12-2.65)), male (OR
      1.99 (95% CI 1.24-3.20)), a higher score on disability (OR 1.00 (95% CI 0.997
      1.02)) and physical component scale (Short-Form 36 (SF-36)) (OR 1.05 (95% CI 1.02
      1.07)), previous rehabilitation (OR 1.85 (95% CI 1.14-2.98)), not receiving
      sickness benefits (OR 0.52 (95% CI 0.24-1.10)) and more work-participation (OR
      4.86 (95% CI 2.35-10.04)). More work-participation (OR 5.22 (95% CI 3.47-7.85))
      and male sex (OR 1.79 (95% CI 1.25-2.55)) were also prognostic factors at 12
      month follow-up. CONCLUSION: At 12 months 52% of patients reported >= 90% work
      participation. The strongest prognostic factor was more work-participation at
      baseline for the recovery of chronic non-specific low back pain.

PMID- 26306821
TI  - Rapamycin improves motor function, reduces 4-hydroxynonenal adducted protein in
      brain, and attenuates synaptic injury in a mouse model of synucleinopathy.
AB  - BACKGROUND: Synucleinopathy is any of a group of age-related neurodegenerative
      disorders including Parkinson's disease, multiple system atrophy, and dementia
      with Lewy Bodies, which is characterized by alpha-synuclein inclusions and
      parkinsonian motor deficits affecting millions of patients worldwide. But there
      is no cure at present for synucleinopathy. Rapamycin has been shown to be
      neuroprotective in several in vitro and in vivo synucleinopathy models. However,
      there are no reports on the long-term effects of RAPA on motor function or
      measures of neurodegeneration in models of synucleinopathy. METHODS: We
      determined whether long-term feeding a rapamycin diet (14 ppm in diet; 2.25 mg/kg
      body weight/day) improves motor function in neuronal A53T alpha-synuclein
      transgenic mice (TG) and explored underlying mechanisms using a variety of
      behavioral and biochemical approaches. RESULTS: After 24 weeks of treatment,
      rapamycin improved performance on the forepaw stepping adjustment test,
      accelerating rotarod and pole test. Rapamycin did not alter A53T alpha-synuclein
      content. There was no effect of rapamycin treatment on midbrain or striatal
      monoamines or their metabolites. Proteins adducted to the lipid peroxidation
      product 4-hydroxynonenal were decreased in brain regions of both wild-type and TG
      mice treated with rapamycin. Reduced levels of the presynaptic marker
      synaptophysin were found in several brain regions of TG mice. Rapamycin
      attenuated the loss of synaptophysin protein in the affected brain regions.
      Rapamycin also attenuated the loss of synaptophysin protein and prevented the
      decrease of neurite length in SH-SY5Y cells treated with 4-hydroxynonenal.
      CONCLUSION: Taken together, these data suggest that rapamycin, an FDA approved
      drug, may prove useful in the treatment of synucleinopathy.

PMID- 26306823
TI  - Strabismus and Micro-Opsoclonus in Machado-Joseph Disease.
AB  - We describe novel deficits of gaze holding and ocular alignment in patients with
      spinocerebellar ataxia type 3, also known as Machado-Joseph disease (MJD). Twelve
      MJD patients were studied. Clinical assessments and quantitative ocular alignment
      measures were performed. Eye movements were quantitatively assessed with corneal
      curvature tracker and video-oculography. Strabismus was seen in ten MJD patients.
      Four patients had mild to moderate intermittent exotropia, three had esotropia,
      one had skew deviation, one had hypotropia, and one patient had moderate
      exophoria. Three strabismic patients had V-pattern. Near point of convergence was
      normal in two out of three patients with exotropia. Gaze holding deficits were
      also common. Eight patients had gaze-evoked nystagmus, and five had micro
      opsoclonus. Other ocular motor deficits included saccadic dysmetria in eight
      patients, whereas all had saccadic interruption of smooth pursuit. Strabismus and
      micro-opsoclonus are common in MJD. Coexisting ophthalmoplegia or vergence
      abnormalities in our patients with exotropia that comprised 50 % of the cohort
      could not explain the type of strabismus in our patients. Therefore, it is
      possible that involvement of the brainstem, the deep cerebellar nuclei, and the
      superior cerebellar peduncle are the physiological basis for exotropia in these
      patients. Micro-opsoclonus was also common in MJD. Brainstem and deep cerebellar
      nuclei lesion also explains micro-opsoclonus, whereas brainstem deficits can
      describe slow saccades seen in our patients with MJD.

PMID- 26306822
TI  - The effectiveness of the Herbst appliance for patients with Class II
      malocclusion: a meta-analysis.
AB  - OBJECTIVE: To systematically investigate review in literature the effects of the
      Herbst appliance for patients with Class II malocclusion patients. METHOD: We
      performed a comprehensive literature survey on PubMed, Web of Science, Embase,
      CENTRAL, SIGLE, and ClinicalTrial.gov up to December 2014. The selection
      criteria: randomized controlled trials or clinical controlled trials; using any
      kind of Herbst appliances to correct Class II division 1 malocclusions; skeletal
      and/or dental changes evaluated through lateral cephalograms. And the exclusion
      criteria: syndromic patients; individual case reports and series of cases;
      surgical interventions. Article screening, data extraction, assessment of risk of
      bias, and evaluation of evidence quality through GRADE were conducted
      independently by two well-trained orthodontic doctors. Consensus was made via
      group discussion of all authors when there is inconsistent information from the
      two. After that, sensitivity analysis and subgroup analysis were performed to
      evaluate the robustness of the meta-analysis. RESULTS: Twelve clinical controlled
      trials meet the above-mentioned criteria, and were included in this analysis. All
      included studies have eleven measures taken during both active treatment effect
      and long term effect periods, including four angular ones (i.e., SNA, SNB, ANB,
      mandibular plane angle) and seven linear ones (i.e. Co-Go, Co-Gn, overjet,
      overbite, molar relationship, A point-OLp, Pg-OLp) during active treatment effect
      period were statistically pooled. Meta-analysis and sensitivity analysis
      demonstrated that all these measures showed consistent results except for SNA,
      ANB, and overbite. Subgroup analysis showed significant changes in SNA, overbite,
      and Pg-OLp. Publication bias was detected in SNB, mandibular plane angle, and A
      point-OLp. CONCLUSION: The Herbst appliance is effective for patients with Class
      II malocclusion in active treatment period. Especially, there are obvious changes
      on dental discrepancy and skeletal changes on Co-Gn. As to its long-term effects,
      more evidence is needed to draw conclusions.

PMID- 26306824
TI  - Learning performances and vulnerability to amyloid toxicity in the
      butyrylcholinesterase knockout mouse.
AB  - Butyrylcholinesterase (BChE) is an important enzyme for detoxication and
      metabolism of ester compounds. It also hydrolyzes the neurotransmitter
      acetylcholine (ACh) in pathological conditions and may play a role in Alzheimer's
      disease (AD). We here compared the learning ability and vulnerability to Abeta
      toxicity in male and female BChE knockout (KO) mice and their 129Sv wild-type
      (Wt) controls. Animals tested for place learning in the water-maze showed
      increased acquisition slopes and presence in the training quadrant during the
      probe test. An increased passive avoidance response was also observed for males.
      BChE KO mice therefore showed enhanced learning ability in spatial and non
      spatial memory tests. Intracerebroventricular (ICV) injection of increasing doses
      of amyloid-beta[25-35] (Abeta25-35) peptide oligomers resulted, in Wt mice, in
      learning and memory deficits, oxidative stress and decrease in ACh hippocampal
      content. In BChE KO mice, the Abeta25-35-induced deficit in place learning was
      attenuated in males and blocked in females. No change in lipid peroxidation or
      ACh levels was observed after Abeta25-35 treatment in male or female BChE KO
      mice. These data showed that the genetic invalidation of BChE in mice augmented
      learning capacities and lowered the vulnerability to Abeta toxicity. 

PMID- 26306825
TI  - Prefrontal cortex stroke induces delayed impairment in spatial memory.
AB  - Stroke is the leading cause of long-term disability. Little is known about the
      effects of stroke on cognitive deficits. The subtle nature of cognition and its
      respective domains in areas such as working memory and attention can make this
      difficult to diagnose and treat. We aimed to establish a model of focal ischemia
      that targets the prefrontal cortex (PFC) and induce memory impairments. Stroke
      and sham mice were assessed at one and four-weeks post-stroke on various tests:
      open-field task to assess activity; grid-walk and cylinder task to assess motor
      impairments; elevated plus maze to assess anxiety; novel-object and object
      location recognition tasks to assess memory impairment. Stroke mice in the open
      field showed a small increase in activity with no effects on gross motor tasks or
      anxiety levels (P >= 0.05) at one and four-weeks post-stroke. Assessment of
      stroke mice on the novel object task showed no differences at either one or four
      weeks compared to sham mice (P >= 0.05). However, assessment of stroke mice on
      the object-location recognition task revealed a significant (P >= 0.05)
      impairment in spatial memory by four-weeks compared to controls. Further, we show
      that stroke results in a small decrease in volume of the medial dorsal nucleus of
      the thalamus (P >= 0.05). This is the first evidence that demonstrates stroke to
      the PFC results in delayed onset impairment in spatial memory, similar to
      findings in human epidemiological data. We suggest that this model may be a
      useful tool in assessing potential rehabilitative/cognitive therapies after
      stroke.

PMID- 26306828
TI  - Climate change-associated tree mortality increases without decreasing water
      availability.
AB  - Temporal increases of tree mortality have been observed in regions where global
      warming has decreased long-term water availability and/or induced droughts.
      However, temporal decreases in water availability are not a global phenomenon.
      Understanding how water deficit-free forests respond to the recent effects of
      climate change is paramount towards a full appreciation of the impacts of climate
      change on global forests. Here, we reveal temporally increasing tree mortality
      across all study species over the last three decades in the central boreal
      forests of Canada, where long-term water availability has increased without
      apparent climate change-associated drought. In addition, we find that the effects
      of conspecific tree-to-tree competition have intensified temporally as a
      mechanism for the increased mortality of shade-intolerant tree species. Our
      results suggest that the consequences of climate change on tree mortality are
      more profound than previously thought.

PMID- 26306826
TI  - Corticotropin releasing factor impairs sustained attention in male and female
      rats.
AB  - Stressful life events and stress-related psychiatric disorders impair sustained
      attention, the ability to monitor rare and unpredictable stimulus events over
      prolonged periods of time. Despite the link between stress and attentional
      disruptions, the neurobiological basis for stress regulation of attention systems
      remains underexplored. Here we examined whether corticotropin releasing factor
      (CRF), which orchestrates stress responses and is hypersecreted in patients with
      stress-related psychiatric disorders, impairs sustained attention. To this end,
      male and female rats received central infusions of CRF prior to testing on an
      operant sustained attention task (SAT), where rats were trained to discriminate
      signaled from non-signaled events. CRF caused a dose-dependent decrease in SAT
      performance in both male and female rats. Females were more impaired than males
      following a moderate dose of CRF, particularly during the middle part of the
      session. This sex difference was moderated by ovarian hormones. Females in the
      estrous cycle stage characterized by lower ovarian hormones had a greater CRF
      induced attentional impairment than males and females in other cycle stages.
      Collectively, these studies highlight CRF as a critical stress-related factor
      that can regulate attentional performance. As sustained attention subserves other
      cognitive processes, these studies suggest that mitigating high levels of CRF in
      patients with stress-related psychiatric disorders may ameliorate their cognitive
      deficits. 

PMID- 26306827
TI  - Medial orbitofrontal cortex lesion prevents facilitatory effects of d-cycloserine
      during fear extinction.
AB  - Animal models of fear extinction have an important clinical relevance to
      pharmacological and exposure-based therapies for anxiety disorders. Lesions of
      prefrontal structures impair fear extinction. On the other hand, d-cycloserine is
      able to enhance this process. We hypothesize that the integrity of cortical
      structures involved in inhibitory control of emotional responses is crucial for
      the facilitatory effects of d-cycloserine. Here, we showed that medial
      orbitofrontal cortex lesion prevents d-cycloserine enhancement of fear
      extinction. These preliminary results suggest that effects of pharmacological
      treatments could be dependent on cortical activity state to promote fear memory
      reduction. 

PMID- 26306830
TI  - Beryllium in exhaled breath condensate as a biomarker of occupational exposure in
      a primary aluminum production plant.
AB  - OBJECTIVE: Low beryllium exposure can induce pulmonary granulomatosis, so called
      berylliosis. For occupational health monitoring, it is more relevant to assess
      the internal dose of Be received by the lungs than urinary or atmospheric Be.
      Exhaled breath condensate (EBC) is a matrix collected non-invasively that derives
      from the airway lining fluid. EBC beryllium (Be) levels were evaluated as a
      marker of occupational exposure in a primary aluminum production plant. METHODS:
      We collected urine and EBC from controls and workers recently exposed to
      beryllium in the pot room and the anode repair sectors, and calculated a
      cumulative beryllium exposure index (CBEI) summing the number of years of
      employment in each task and multiplying by the estimated average beryllium
      exposure for the task. Concentrations of beryllium and aluminum were measured in
      EBC (Be-EBC and Al-EBC) and in urine (Be-U and Al-U) by ICP-MS. RESULTS AND
      CONCLUSION: We have shown that it was possible to measure Be and Al in workers'
      EBC. Compared with controls and after adjustment for smoking status, levels of Be
      EBC and Al-EBC were higher in pot room workers and exposed subjects,
      respectively. Due to its relationship with CBEI, but not with Be-U, it appears
      that Be-EBC could be a promising marker of occupational exposure and provide
      additional toxicokinetic information in occupational health studies.

PMID- 26306829
TI  - Comparison of age-specific patterns of sexual behaviour and anal HPV prevalence
      in homosexual men with patterns in women.
AB  - OBJECTIVES: Anal human papillomavirus (HPV) is highly prevalent in men who have
      sex with men (MSM) of all ages, whereas cervical HPV declines with age. We
      explore the hypothesis that different sexual behavioural patterns are the basis
      of this difference in age distribution. METHODS: Published data on age-specific
      HPV prevalence for women (cervical HPV) were extracted from a large meta-analysis
      and for MSM (anal HPV) from the EXPLORE study of HIV-negative MSM. Age-specific
      data on recent sexual activity were extracted from two behavioural surveys: the
      second Australian Study of Health and Relationships survey and the 2013 Gay
      Community Periodic Survey. RESULTS: At least 50% of MSM at all ages reported more
      than one sexual partner in the past 6 months. In comparison, 33% of women aged 16
      19 years reported more than one partner over the past year. This decreased to 19%
      and 6% in women aged 20-29 and 30-39 years, respectively, and to fewer than 5% of
      women in older age groups. Prevalent anal HPV was detected in over 50% of MSM in
      each age group. Prevalence did not decline with age. In contrast, there was a
      steady decrease in cervical HPV prevalence with age. Cervical HPV prevalence fell
      from 23% among North American women aged <25 years to 3% in women aged >=65
      years. CONCLUSIONS: In contrast to the decreasing prevalence with age among
      heterosexual women, the high prevalence and lack of decline in prevalent anal HPV
      among older MSM are likely to be related to continuing high rates of newly
      acquired HPV infection from ongoing sexual exposure through new partners.

PMID- 26306831
TI  - Biological monitoring of Italian soldiers deployed in Iraq. Results of the SIGNUM
      project.
AB  - BACKGROUND: Leukemia/lymphoma cases reported in 2001 among United Nation soldiers
      or peacekeepers deployed to the Balkans aroused alert on the exposure to depleted
      uranium. Recent epidemiological studies carried out in different European
      countries among peacekeepers who served in the Balkans failed to demonstrate a
      higher than expected risk of all cancers but, mostly due to their limitations in
      size and follow up time, leave open the debate on health risk of depleted
      uranium. The aim of SIGNUM (Study of the Genotoxic Impact in Military Units) was
      to identify potential genotoxic risk associated with the exposure to depleted
      uranium or other pollutants in the Italian Army military personnel deployed in
      Iraq. METHODS: Blood and urine samples were collected before and after the
      deployment from 981 Italian soldiers operating in Iraq in 2004-2005. As, Cd, Mo,
      Ni, Pb, U, V, W, and Zr were determined in urine and serum. DNA-adducts, 8
      hydroxy-2'-deoxyguanine and micronuclei frequency were evaluated in blood
      lymphocytes. Three different genetic polymorphisms, GSTM1, XRCC1, OGG1 were
      analyzed. RESULTS: Significant T0-T1 reduction in the total concentration of
      uranium, increases for Cd, Mo, Ni, Zr, and decreases for As, Pb, W, and V in
      urine and plasma were observed. Increases in oxidative alterations and in
      micronuclei frequency, included in the range of values of non-occupationally
      exposed populations, were observed at the end of the period of employment.
      CONCLUSIONS: Our results did not detect any toxicologically relevant variation of
      DNA-damage biomarkers related to the deployment in the operational theater.

PMID- 26306832
TI  - Neuroprotective therapies in glaucoma: I. Neurotrophic factor delivery.
AB  - Glaucoma is a neurodegenerative eye disease that causes permanent blindness at
      the progressive stage and the number of people affected worldwide is expected to
      reach over 79 million by 2020. Currently, glaucoma management relies on
      pharmacological and invasive surgical treatments mainly by reducing the
      intraocular pressure (IOP), which is the most important risk factor for the
      progression of the visual field loss. Recent research suggests that
      neuroprotective or neuroregenerative approaches are necessary to prevent retinal
      ganglion cells (RGCs) loss and visual impairment over time. Neuroprotection is a
      new therapeutic strategy that attempts to keep RGCs alive and functional. New
      gene and cell therapeutics encoding neurotrophic factors (NTFs) are emerging for
      both neuroprotection and regenerative treatments for retinal diseases. This
      article briefly reviews the role of NTFs in glaucoma and the potential delivery
      systems.

PMID- 26306833
TI  - Synthesis of Ordered Mesoporous Carbon Materials by Dry Etching.
AB  - A novel synthesis method for ordered mesoporous carbons is presented. The inverse
      replication of a silica template was achieved using the carbonization of sucrose
      within mesoporous KIT-6. Instead of liquid acid etching, as in classical
      nanocasting, a novel dry chlorine etching procedure for template removal is
      presented for the first time. The resultant ordered mesostructured carbon
      material outperforms carbons obtained by conventional hard templating with
      respect to high specific micro- and mesopore volumes (0.6 and 1.6 cm(3) g(-1) ,
      respectively), due to the presence of a hierarchical pore system. A high specific
      surface area of 1671 m(2) g(-1) was achieved, rendering this synthesis route a
      highly convenient method to produce ordered mesoporous carbons.

PMID- 26306834
TI  - Degree of Cajal-Retzius Cell Mislocalization Correlates with the Severity of
      Structural Brain Defects in Mouse Models of Dystroglycanopathy.
AB  - The secondary dystroglycanopathies are characterized by the hypoglycosylation of
      alpha dystroglycan, and are associated with mutations in at least 18 genes that
      act on the glycosylation of this cell surface receptor rather than the Dag1 gene
      itself. At the severe end of the disease spectrum, there are substantial
      structural brain defects, the most striking of which is often cobblestone
      lissencephaly. The aim of this study was to determine the gene-specific aspects
      of the dystroglycanopathy brain phenotype through a detailed investigation of the
      structural brain defects present at birth in three mouse models of
      dystroglycanopathy-the FKRP(KD) , which has an 80% reduction in Fkrp transcript
      levels; the Pomgnt1null , which carries a deletion of exons 7-16 of the Pomgnt1
      gene; and the Large(myd) mouse, which carries a deletion of exons 5-7 of the
      Large gene. We show a rostrocaudal and mediolateral gradient in the severity of
      brain lesions in FKRP(KD) , and to a lesser extent Pomgnt1null mice. Furthermore,
      the mislocalization of Cajal-Retzius cells is correlated with the gradient of
      these lesions and the severity of the brain phenotype in these models. Overall
      these observations implicate gene-specific differences in the pathogenesis of
      brain lesions in this group of disorders.

PMID- 26306835
TI  - Emerging Pharmacological Treatments to Prevent Abdominal Aortic Aneurysm Growth
      and Rupture.
AB  - Abdominal aortic aneurysm (AAA) is a local expansion of the abdominal aorta wall
      caused by a complex multifactorial maladaptive vascular remodeling. Despite
      recent advances in the management of cardiovascular diseases, there currently is
      no established drug therapy for AAA. Since the probability of death from a
      ruptured AAA still remains high, preventive elective repair of AAAs larger than
      5.5 cm in luminal diameter is considered the best treatment option. However,
      perioperative complications are problematic as elective AAA repair comes with
      numerous intrinsic risks. Impelled by the need of improving AAA therapy,
      significant efforts have been made to identify pharmacological tools that would
      slow down AAA enlargement and lower the risk of rupture, thereby reducing the
      necessity of surgical intervention. In this review, we discuss recent findings
      addressing molecular targets that could potentially treat AAA, particularly
      addressing: statins, classical renin angiotensin system (RAS) blockers, the
      protective arm of RAS, renin inhibitors, tetracyclines, interleukin-1beta
      inhibition, anti-angiogenic agents and urocortins.

PMID- 26306836
TI  - Abdominal Aortic Aneurysm: What About Screening?
AB  - The prevalence of abdominal aortic aneurysm (AAA) in general population is 4-9%
      with a high mortality rate when ruptured. Therefore, screening programs were
      developed in many countries to detect small and large AAA in selected patients.
      Indeed, prevalence of AAA increases in patients over 65 years old with cigarette
      smoking history. This paper reviews recent literature related to AAA screening
      focusing on epidemiology, screening tests and evidence based medicine to
      highlight not only advantages but also disadvantages of screening programs among
      population. 

PMID- 26306837
TI  - Dissecting abdominal aortic aneurysm in Angiotensin II-infused mice: the
      importance of imaging.
AB  - INTRODUCTION: Since the initial publication in 2000, Angiotensin II-infused mice
      have become one of the most popular models to study abdominal aortic aneurysm in
      a pre-clinical setting. We recently used phase contrast X-ray based computed
      tomography to demonstrate that these animals develop an apparent luminal
      dilatation and an intramural hematoma, both related to mural ruptures in the
      tunica media in the vicinity of suprarenal side branches. AIMS: The aim of this
      narrative review was to provide an extensive overview of small animal applicable
      techniques that have provided relevant insight into the pathogenesis and
      morphology of dissecting AAA in mice, and to relate findings from these
      techniques to each other and to our recent PCXTM-based results. Combining
      insights from recent and consolidated publications we aimed to enhance our
      understanding of dissecting AAA morphology and anatomy. RESULTS AND CONCLUSION:
      We analyzed in vivo and ex vivo images of aortas obtained from macroscopic
      anatomy, histology, high-frequency ultrasound, contrast-enhanced micro-CT, micro
      MRI and PCXTM. We demonstrate how in almost all publications the aorta has been
      subdivided into a part in which an intact lumen lies adjacent to a remodeled
      wall/hematoma, and a part in which elastic lamellae are ruptured and the lumen
      appears to be dilated. We show how the novel paradigm fits within the existing
      one, and how 3D images can explain and connect previously published 2D
      structures. We conclude that PCXTM-based findings are in line with previous
      results, and all evidence points towards the fact that dissecting AAAs in
      Angiotensin II-infused mice are actually caused by ruptures of the tunica media
      in the immediate vicinity of small side branches.

PMID- 26306838
TI  - The Role of Endothelial Dysfunction in Aortic Aneurysms.
AB  - Abdominal aortic aneurysm is a vascular disease which, despite the fact that it
      shares common risk factors with atherosclerosis, develops in parallel but as a
      partly independent process, through different pathogenic mechanisms. The
      pathogenic mechanisms involve metalloproteinase and collagenase activation,
      median and adventitial degradation, elastin lysis, vascular smooth cells
      transformation and apoptosis, collagen production and lysis imbalance combined
      with excessive inflammatory infiltration. Endothelial cells respond to a number
      of stimulating factors, including smoking, hypertension and AT1 receptor
      stimulation and non-uniform distribution of wall stress. Their ability to produce
      NO is crucial in order to adapt. Endothelial cells contribute to AAA development
      due to increased oxidative stress which is partly mediated by impaired NO
      bioavailability due to endothelial dysfunction and NADPH oxidase overexpression.
      In addition, they express several molecules among which adherence molecules,
      selectins, endothelin-1, regulating inflammatory infiltration and oxidative
      stress. Inflammatory cells consist of monocytes, polymorphonuclear neutrophils
      and lymphocytes and they are involved in the degrading process in the aortic wall
      by secreting proteolytic enzymes or by releasing interleukins which mediate the
      inflammation response. Endothelial dysfunction and arterial stiffness reflect on
      indices like FMD, carotid-femoral PWV and augmentation index, sometimes with
      controversial results. At present, surgical treatment is the only option provided
      in patients with large AAA, in particular. Focusing on the emerging role of
      endothelial cells in AAA pathology may contribute in creating new therapeutic
      options in a disease which has not yet a well-accepted, implemented
      pharmaceutical treatment.

PMID- 26306839
TI  - Monocytes, Macrophages and Other Inflammatory Mediators of Abdominal Aortic
      Aneurysm.
AB  - Macrophages early invade the forming abdominal aortic aneurysm (AAA) and greatly
      contribute to its pathogenesis. Recent findings have shown that Ly-6C(high) and
      Ly-6C(low) monocytes are rapidly mobilized from the splenic reservoir in response
      to angiotensin II infusion and sequentially infiltrate the abdominal aorta. The
      first wave of Ly-6C(high) monocytes prevails in the aorta and promotes the
      accumulation of inflammatory macrophages, which most likely cause irreversible
      changes in the abdominal aorta. In this review, we discuss the current knowledge
      on the cellular mechanisms that initiate AAA in mice. We particularly focus on
      the role of monocyte and macrophage subsets during the early steps of the
      aneurysmal process. 

PMID- 26306840
TI  - Angiotensin II and Abdominal Aortic Aneurysms: An update.
AB  - Abdominal aortic aneurysm (AAA) is a devastating disease associated with high
      prevalence of death due to aortic rupture. Currently the therapy is restricted to
      surgical procedures to prevent aortic rupture, which in turn has a risk for
      postoperative mortality. There are no proven pharmacological therapies available
      to prevent expansion or rupture of AAA due to the paucity of knowledge on the
      mechanisms underlying the nature and pathophysiological processes of this complex
      disease. Animal models are powerful tools to provide mechanistic insights into
      understanding the development of AAA. Numerous pharmacological approaches have
      been explored as potential therapies in experimental AAA in the past decade. This
      review overviews recent advances in mechanistic studies of AAA in angiotensin II
      infused mouse models and highlights their clinical relevance for possible
      therapeutic targets. 

PMID- 26306841
TI  - Marfan Syndrome and Related Heritable Thoracic Aortic Aneurysms and Dissections.
AB  - In this overview we aim to address a number of recent insights and developments
      regarding clinical aspects, etiology, and treatment of Heritable Thoracic Aortic
      Disease (H-TAD). We will focus on monogenetic disorders related to aortic
      aneurysms. H-TADs are rare but they provide a unique basis for the study of
      underlying pathogenetic pathways in the complex disease process of aneurysm
      formation. The understanding of pathomechanisms may help us to identify medical
      treatment targets to improve prognosis. Among the monogenetic aneurysm disorders,
      Marfan syndrome is considered as a paradigm entity and many insights are derived
      from the study of clinical, genetic and animal models for Marfan syndrome. We
      will therefore first provide a detailed overview of the various aspects of Marfan
      syndrome after which we will give an overview of related H-TAD entities. 

PMID- 26306842
TI  - Emerging Pharmacological Treatments to Prevent Abdominal Aortic Aneurysm Growth
      and Rupture.
AB  - Abdominal aortic aneurysm (AAA) is a local expansion of the abdominal aorta wall
      caused by a complex multifactorial maladaptive vascular remodeling. Despite
      recent advances in the management of cardiovascular diseases, there currently is
      no established drug therapy for AAA. Since the probability of death from a
      ruptured AAA still remains high, preventive elective repair of AAAs larger than
      5.5 cm in luminal diameter is considered the best treatment option. However,
      perioperative complications are problematic as elective AAA repair comes with
      numerous intrinsic risks. Impelled by the need of improving AAA therapy,
      significant efforts have been made to identify pharmacological tools that would
      slow down AAA enlargement and lower the risk of rupture, thereby reducing the
      necessity of surgical intervention. In this review, we discuss recent findings
      addressing molecular targets that could potentially treat AAA, particularly
      addressing: statins, classical renin angiotensin system (RAS) blockers, the
      protective arm of RAS, renin inhibitors, tetracyclines, interleukin-1beta
      inhibition, anti-angiogenic agents and urocortins. 

PMID- 26306843
TI  - Excessive L-cysteine induces vacuole-like cell death by activating endoplasmic
      reticulum stress and mitogen-activated protein kinase signaling in intestinal
      porcine epithelial cells.
AB  - High intake of dietary cysteine is extremely toxic to animals and the underlying
      mechanism remains largely unknown. This study was conducted to test the
      hypothesis that excessive L-cysteine induces cell death by activating endoplasmic
      reticulum (ER) stress and mitogen-activated protein kinase (MAPK) signaling in
      intestinal porcine epithelial cells. Jejunal enterocytes were cultured in the
      presence of 0-10 mmol/L L-cysteine. Cell viability, morphologic alterations, mRNA
      levels for genes involved in ER stress, protein abundances for glucose-regulated
      protein 78, C/EBP homologous protein (CHOP), alpha subunit of eukaryotic
      initiation factor-2 (eIF2alpha), extracellular signal-regulated kinase (ERK1/2),
      p38 MAPK, and c-Jun N-terminal protein kinase (JNK1/2) were determined. The
      results showed that L-cysteine (5-10 mmol/L) reduced cell viability (P < 0.05)
      and led to vacuole-like cell death in intestinal porcine epithelial cells. These
      adverse effects of L-cysteine were not affected by the autophagy inhibitor 3
      methyladenine. The protein abundances for CHOP, phosphorylated (p)-eIF2alpha, p
      JNK1/2, p-p38 MAPK, and the spliced form of XBP-1 mRNA were enhanced (P < 0.05),
      whereas those for p-ERK1/2 were reduced (P < 0.05). Collectively, excessive L
      cysteine induces vacuole-like cell death via the activation of ER stress and MAPK
      signaling in small intestinal epithelial cells. These signaling pathways may be
      potential targets for developing effective strategies to prevent the toxicity of
      dietary cysteine.

PMID- 26306844
TI  - Detection of COL III in parchment by amino acid analysis.
AB  - Cultural heritage parchments made from the reticular dermis of animals have been
      subject to studies of deterioration and conservation by amino acid analysis. The
      reticular dermis contains a varying mixture of collagen I and III (COL I and
      III). When dealing with the results of the amino acid analyses, till now the COL
      III content has not been taken into account. Based on the available amino acid
      sequences, we present a method for determining the amount of COL III in the
      reticular dermis of new and historical parchments calculated from the ratio of
      Ile/Val. We find COL III contents between 7 and 32 % in new parchments and
      between 0.2 and 40 % in the historical parchments. This is consistent with
      results in the literature. The varying content of COL III has a significant
      influence on the uncertainty of the amino acid analysis. Although we have not
      found a simple correlation between the COL III content and the degree of
      deterioration, our results show that this question must be taken into
      consideration in future studies of the chemical and physical deterioration of
      parchment measured by amino acid analysis and other analytical methods.

PMID- 26306845
TI  - Inclusion of a pH-responsive amino acid-based amphiphile in methotrexate-loaded
      chitosan nanoparticles as a delivery strategy in cancer therapy.
AB  - The encapsulation of antitumor drugs in nanosized systems with pH-sensitive
      behavior is a promising approach that may enhance the success of chemotherapy in
      many cancers. The nanocarrier dependence on pH might trigger an efficient
      delivery of the encapsulated drug both in the acidic extracellular environment of
      tumors and, especially, in the intracellular compartments through disruption of
      endosomal membrane. In this context, here we reported the preparation of chitosan
      based nanoparticles encapsulating methotrexate as a model drug (MTX-CS-NPs),
      which comprises the incorporation of an amino acid-based amphiphile with pH
      responsive properties (77KS) on the ionotropic complexation process. The presence
      of 77KS clearly gives a pH-sensitive behavior to NPs, which allowed accelerated
      release of MTX with decreasing pH as well as pH-dependent membrane-lytic
      activity. This latter performance demonstrates the potential of these NPs to
      facilitate cytosolic delivery of endocytosed materials. Outstandingly, the
      cytotoxicity of MTX-loaded CS-NPs was higher than free drug to MCF-7 tumor cells
      and, to a lesser extent, to HeLa cells. Based on the overall results, MTX-CS-NPs
      modified with the pH-sensitive surfactant 77KS could be potentially useful as a
      carrier system for intracellular drug delivery and, thus, a promising targeting
      anticancer chemotherapeutic agent. 

PMID- 26306846
TI  - Changes in urinary amino acids excretion in relationship with muscle activity
      markers over a professional cycling stage race: in search of fatigue markers.
AB  - The aim of this study was to identify the relationship between metabolic effort,
      muscular damage/activity indices, and urinary amino acids profile over the course
      of a strenuous prolonged endurance activity, as a cycling stage race is, in order
      to identify possible fatigue markers. Nine professional cyclists belonging to a
      single team, competing in the Giro d'Italia cycling stage race, were
      anthropometrically characterized and sampled for blood and urine the day before
      the race started, and on days 12 and 23 of the race. Diet was kept the same over
      the race, and power output and energy expenditure were recorded. Sera were
      assayed for muscle markers (lactate dehydrogenase, aspartate aminotransferase,
      and creatine kinase activities, and blood urea nitrogen), and creatinine, all
      corrected for plasma volume changes. Urines were profiled for amino acid
      concentrations, normalized on creatinine excretion. Renal function, in terms of
      glomerular filtration rate, was monitored by MDRD equation corrected on body
      surface area. Creatine kinase activity and blood urea were increased during the
      race as did serum creatinine while kidney function remained stable. Among the
      amino acids, taurine, glycine, cysteine, leucine, carnosine, 1-methyl histidine,
      and 3-methyl histidine showed a net decreased, while homocysteine was increased.
      Taurine and the dipeptide carnosine (beta-alanyl-L-histidine) were significantly
      correlated with the muscle activity markers and the indices of effort. In
      conclusion, the metabolic profile is modified strikingly due to the effort.
      Urinary taurine and carnosine seem useful tools to evaluate the muscle damage and
      possibly the fatigue status on a long-term basis.

PMID- 26306847
TI  - Comparative study on combined co-pyrolysis/gasification of walnut shell and
      bituminous coal by conventional and congruent-mass thermogravimetric analysis
      (TGA) methods.
AB  - Combined co-pyrolysis/gasification of bituminous coal (BC) and walnut shell (WS)
      are comparatively studied with both conventional and congruent-mass
      thermogravimertric analysis (TGA) methods. The results indicate that BC and WS
      exhibit additivity in the co-pyrolysis step. However, the gasification reactivity
      of chars in subsequent gasification step exhibits remarkable sample-mass
      dependence, which causes the illusions in synergy and inhibition effects when
      conventional TGA tests are conducted. A congruent-mass TGA method has been
      developed to overcome the limitations of the conventional TGA mode. One of the
      advantages of this method is that it can reduce to a minimum the effect of sample
      mass on reactivity. Thus, the degree of synergy or inhibition can be directly
      estimated from the deviation of the experimental TG curves between the two
      separated and blended samples. We recommend this method in studying the co
      processing behavior between coal and biomass. 

PMID- 26306848
TI  - Phosphoribulokinase mediates nitrogenase-induced carbon dioxide fixation gene
      repression in Rhodobacter sphaeroides.
AB  - In many organisms there is a balance between carbon and nitrogen metabolism.
      These observations extend to the nitrogen-fixing, nonsulfur purple bacteria,
      which have the classic family of P(II) regulators that coordinate signals of
      carbon and nitrogen status to regulate nitrogen metabolism. Curiously, these
      organisms also possess a reverse mechanism to regulate carbon metabolism based on
      cellular nitrogen status. In this work, studies in Rhodobacter sphaeroides firmly
      established that the activity of the enzyme that catalyses nitrogen fixation,
      nitrogenase, induces a signal that leads to repression of genes encoding enzymes
      of the Calvin-Benson-Bassham (CBB) CO2 fixation pathway. Additionally, genetic
      and metabolomic experiments revealed that NADH-activated phosphoribulokinase is
      an intermediate in the signalling pathway. Thus, nitrogenase activity appears to
      be linked to cbb gene repression through phosphoribulokinase. 

PMID- 26306850
TI  - Can testosterone therapy be offered to men on active surveillance for prostate
      cancer? Preliminary results.
AB  - This report presents our experience with T therapy in a cohort of T-deficient men
      on active surveillance (AS) for Gleason 3 + 3 and Gleason 3 + 4 prostate cancer
      (PCa). A retrospective chart review identified 28 men with T deficiency who
      underwent T therapy (T group) for at least 6 months while on AS for PCa. A
      comparison group of 96 men on AS for PCa with untreated T deficiency (no-T group)
      was identified at the same institution. The AS protocol followed a modified
      Epstein criteria and allowed inclusion of men with a single core of low-volume
      Gleason 3 + 4 PCa. Mean age was 59.5 and 61.3 years, and mean follow-up was 38.9
      and 42.4 months for the T and no-T groups, respectively. Of all 28 men in the T
      group, 3 (10.7%) men developed an increase in Gleason score while on AS. Of 22
      men in the T group with Gleason 3 + 3 disease, 7 (31.8%) men developed biopsy
      progression including 3 men (13.6%) who developed Gleason 3 + 4 PCa. Of 6 men
      with Gleason 3 + 4 disease at baseline, 2 (33.3%) men developed an increase in
      tumor volume, and none developed upgrading beyond Gleason 3 + 4. All 96 men in
      the no-T group had Gleason 3 + 3 disease at baseline and, 43 (44.7%) developed
      biopsy progression, including 9 men (9.38%) with upgrading to Gleason 7 (3 + 4).
      Biopsy progression rates were similar for both groups and historical controls.
      Biopsy progression in men on AS appears unaffected by T therapy over 3 years.
      Prospective placebo-controlled trials of T therapy in T-deficient men on AS
      should be considered given the symptomatic benefits experienced by treated men. 

PMID- 26306849
TI  - Transcriptome research on spermatogenic molecular drive in mammals.
AB  - It is known that spermatogenic disorders are associated with genetic deficiency,
      although the primary mechanism is still unclear. It is difficult to demonstrate
      the molecular events occurring in testis, which contains germ cells at different
      developmental stages. However, transcriptomic methods can help us reveal the
      molecular drive of male gamete generation. Many transcriptomic studies have been
      performed on rodents by utilizing the timing of the first wave of
      spermatogenesis, which is not a suitable strategy for research in fertile men.
      With the development of separation methods for male germ cells, transcriptome
      research on the molecular drive of spermatogenesis in fertile men has seen great
      progress, and the results could be ultimately applied to improve the diagnosis
      and treatment for male infertility. 

PMID- 26306851
TI  - Androgen receptor splice variants and polycystic ovary syndrome: cause or effect?

PMID- 26306852
TI  - Phosphatidylcholine's functions beyond that of a membrane brick.
AB  - Since its discovery in the 19th century, phosphatidylcholine (PC) has been
      regarded primarily as a structural lipid. However, more recent evidence, much of
      it in the last five years, strongly suggests that PC has other roles. Here, we
      explore some of that new evidence and consider the possibility that the ultimate
      role of phosphatidylcholine may not be predictable. 

PMID- 26306853
TI  - Women make up majority of trainees in seven US specialties.

PMID- 26306854
TI  - Long-term results after modified Epping procedure for trapeziometacarpal
      osteoarthritis.
AB  - INTRODUCTION: Thumb trapeziometacarpal joint (TMJ) arthritis is among the most
      common degenerative joint diseases of the hand and predominantly affects patients
      in their fifth or sixth decade of life. Mid-term results of the most common
      surgical procedures were inconclusive regarding the superiority of one particular
      treatment method. This study presents the long-term outcomes of a modified Epping
      procedure. METHODS: Seventy-one patients underwent a modified Epping procedure
      with a flexor carpi radialis (FCR) tendon sling stabilizer. After a mean follow
      up of 13 years, 39 patients were followed by questionnaire and 15 patients
      presented for clinical examination. Outcomes were evaluated by objective clinical
      measurements, radiographic evaluations, performance in DASH, as well as patients'
      perceived level of handicap during defined exercises. RESULTS: Mean DASH score
      was 32.39. Within the cohort, 66.7 % of the patients were free of complaints.
      Among patients reporting complaints, perceived loss of strength was the main
      concern for the majority (15.4 %) of study participants. Grip and pinch strengths
      and range of motion did not differ significantly between operated and non
      operated hands. One patient suffered rupture of ligament plasty and needed
      revision surgery. CONCLUSION: Despite relatively high DASH scores, the overall
      outcome of the modified Epping procedure is encouraging. Subjective loss of
      strength is a main complaint among patients, whereas instability is less of
      concern.

PMID- 26306856
TI  - Transcriptional changes in three immunoglobulin isotypes of rohu, Labeo rohita in
      response to Argulus siamensis infection.
AB  - Immunoglobulin heavy chains of three isotypes viz., IgM, IgD and IgT/IgZ are
      described in teleosts. In this study, a challenge experiment with an ectoparasite
      Argulus siamensis was conducted to evaluate the changes in adaptive immune
      response by quantitation of expression of Ig heavy chains in skin, head kidney
      and mucus of infected rohu, Labeo rohita. Rohu were challenged with 100
      metanauplii of A. siamensis/fish. Head kidney, skin and mucus samples were
      collected at 0 h, 12 h, 24 h, 3 d, 7 d, 15 d and 30 d by sacrificing four fish
      each from infected and control groups at each time point. The expression of IgM,
      IgD and IgZ in these tissues were measured by reverse transcription real time
      quantitative PCR. IgM level was found to reach its peak significantly 30 d post
      infection in head kidney tissue, while IgM transcripts were below detectable
      range in skin and mucus at all time points. IgZ and IgD levels were significantly
      up-regulated post-infection in all the three tissue samples. Early up-regulation
      of IgD was observed in skin and mucus, compared to head kidney. This study showed
      that parasitic invasion can trigger varied expressions of immunoglobulin types to
      provide systemic as well as local protection in the host. In particular, the
      appearance of high level of expression of IgZ and IgD in skin and mucus will pave
      the way for vaccine development against A. siamensis which feeds on those
      tissues.

PMID- 26306855
TI  - Exogenous phospholipids supplementation improves growth and modulates immune
      response and physical barrier referring to NF-kappaB, TOR, MLCK and Nrf2
      signaling factors in the intestine of juvenile grass carp (Ctenopharyngodon
      idella).
AB  - This study was conducted to investigate the effects of dietary phospholipids (PL)
      on the growth performance, intestinal enzyme activity and immune response and
      intestinal physical barrier of juvenile grass carp (Ctenopharyngodon idella). A
      total of 1080 juvenile grass carp with an average initial weight of 9.34 +/- 0.03
      g were fed six semi-purified diets containing 0.40% (unsupplemented control
      group), 1.43%, 2.38%, 3.29%, 4.37% and 5.42% PL for 2 months. Results indicated
      that 3.29% PL increased lysozyme (LZ) and acid phosphatase (ACP) activities and
      complement component 3 (C3) content (P < 0.05), up-regulated the mRNA relative
      expression levels of interleukin 10, transforming growth factor beta1 (TGF
      beta1), inhibitor protein kappaBalpha (IkappaBalpha), target of rapamycin (TOR)
      and casein kinase 2 (CK2) (P < 0.05), and down-regulated tumor necrosis factor
      alpha (TNF-alpha), interleukin 1beta, nuclear factor kappaB p65 (NF-kappaB p65),
      IkappaB kinase beta (IKKbeta) and IkappaB kinase gamma (IKKgamma) mRNA relative
      expression levels (P < 0.05) in the intestine, suggesting that optimum PL could
      improve fish intestinal immunity. In addition, 3.29% PL increased the activities
      of anti-superoxide anion (ASA), anti-hydroxyl radical, copper/zinc superoxide
      dismutase (SOD1), glutathione peroxidase (GPx) and glutathione reductase (GR),
      the content of glutathione (P < 0.05), and the mRNA relative expression levels of
      occludin, zonula occludens 1 (ZO-1), claudin 3, claudin 12, claudin b, claudin c,
      SOD1, GPx, GR and NF-E2-related factor 2 (Nrf2) and decreased malondialdehyde
      (MDA), protein carbonyl (PC) and ROS content (P < 0.05), the mRNA relative
      expression levels of Kelch-like-ECH-associated protein 1a (Keap1a), myosin light
      chain kinase (MLCK) and p38 mitogen-activated protein kinase (p38 MAPK) in the
      intestine, indicating that the optimum PL could improve fish intestinal physical
      barrier. Finally, based on the PWG, C3 content in the DI, ACP activity in the DI,
      intestinal PC content and intestinal ASA activity, the optimal dietary PL levels
      for juvenile grass carp (9.34-87.50 g) were estimated to be 3.46%, 3.79%, 3.93%,
      3.72%, and 4.12%, respectively.

PMID- 26306857
TI  - Effects of light intensity on growth, immune responses, antioxidant capability
      and disease resistance of juvenile blunt snout bream Megalobrama amblycephala.
AB  - Light is necessary for many fish species to develop and grow normally since most
      fishes are visual feeders. However, too intense light may be stressful or even
      lethal. Thus, this study was conducted to evaluate the effect of light intensity
      on growth, immune response, antioxidant capability and disease resistance of
      juvenile blunt snout bream Megalobrama amblycephala. Fish (18.04 +/- 0.22 g)
      randomly divided into 5 groups were exposed to a range of light intensities (100,
      200, 400, 800 and 1600 lx) in cultures for 8 weeks. After the feeding trial, fish
      were challenged by Aeromonas hydrophila and cumulative mortality was recorded for
      the next 96 h. The results demonstrated that fish subjected to 400 lx showed the
      greatest weight gain (125.70 +/- 5.29%). Plasma levels of glucose and lactate
      increased with light intensity rising from 100 lx to 1600 lx while the lowest
      plasma levels of cortisol was observed at 400 lx group. Post-challenged haemato
      immunological parameters (including plasma lysozyme and alternative complement
      activities, as well as plasma nitric oxide level and globulin contents) improved
      with light intensity increasing from 100 lx to 400 lx, and then decreased with
      further increasing light intensity. However, antioxidant biomarkers such as liver
      catalase and malondialdehyde showed an opposite trend with immune response with
      the lowest values observed at 400 lx groups. The application of light intensity
      at 1600 lx significantly lowered liver glutathione activity to 76.78 +/- 6.91
      MUmol g(-1). Within a range of light intensity from 100 to 400 lx, no differences
      were observed in liver total superoxide dismutase and glutathione peroxidase
      activities while they were significantly higher at 800 and 1600 lx. After
      challenge, the lowest mortality was observed in fish exposed to 400 lx. It was
      significantly lower than that of fish exposed to 100 and 1600 lx. The results of
      the present study indicated that high light intensities (more than 800 lx) not
      only produced poor growth, but also led to stress response, as might consequently
      result in the elevated liver oxidation rates and depress immunity of this
      species. Although no stress response was observed, fish subjected to low light
      intensities (lower than 400 lx) also showed oxidative stress, immunosuppression
      and reduced disease resistance. Taken together, the optimal light intensity to
      enhance growth and boost immunity of this species at juvenile stage is 400 lx.

PMID- 26306858
TI  - Subversion of plant cellular functions by bacterial type-III effectors: beyond
      suppression of immunity.
AB  - Most bacterial plant pathogens employ a type-III secretion system to inject type
      III effector (T3E) proteins directly inside plant cells. These T3Es manipulate
      host cellular processes in order to create a permissive niche for bacterial
      proliferation, allowing development of the disease. An important role of T3Es in
      plant pathogenic bacteria is the suppression of plant immune responses. However,
      in recent years, research has uncovered T3E functions different from direct
      immune suppression, including the modulation of plant hormone signaling,
      metabolism or organelle function. This insight article discusses T3E functions
      other than suppression of immunity, which may contribute to the modulation of
      plant cells in order to promote bacterial survival, nutrient release, and
      bacterial replication and dissemination.

PMID- 26306860
TI  - Variations in maternal behavior in rats selected for infant ultrasonic
      vocalization in isolation.
AB  - Individual differences in maternal behavior in rodents are associated with
      altered physiology and behavior in offspring across their lifespan and across
      generations. Offspring of rat dams that engage in high frequencies of high-arched
      back nursing and pup-licking (High-LG) show attenuated stress responses compared
      to those engaging in lower frequencies (Low-LG). Selective breeding also produces
      widespread alterations in physiology and behavior that are stable over
      generations. To examine processes underlying generational and developmental
      influences on anxiety in an animal model, we developed two lines of rats that
      emit either extremely high (High-USV) or low (Low-USV) rates of 45kHz ultrasonic
      vocalizations in isolation at postnatal day 10. Compared to the Low-USV line,
      High-USV rats display increased indices of anxiety- and depression-like behavior
      in adulthood. The current study assessed maternal behaviors as well as oxytocin
      and vasopressin receptor density in High-USV and Low-USV dams to determine if
      selective breeding had produced differences that paralleled those found in Low-
      and High-LG dams. We found that Low-USV dams engage in more high-arched nursing
      and pup-licking than High-USV dams. Differences in oxytocin and vasopressin
      receptor levels were not widespread throughout the brain, with line differences
      in the piriform cortex and nucleus accumbens. This research illustrates the
      potential interplay between genetically determined (USV line) and environmental
      (postnatal mother-infant interactions) factors in accounting for the phenotypes
      associated with maternal separation induced postnatal vocalizations. 

PMID- 26306859
TI  - Quantifying disparities in cancer incidence and mortality of Australian residents
      of New South Wales (NSW) by place of birth: an ecological study.
AB  - BACKGROUND: In 2013, about 32% of the Australian population over 15 years of age
      was born overseas. Previous cancer-related immigrant health studies identified
      differences in mortality and incidence between immigrants and Australian-born
      people. To identify groups that may require targeted interventions, we describe
      by region of birth: 1. the highest cancer incidence and mortality rates for NSW
      residents, Australia's most populous state; and 2. mortality to incidence ratios
      (MIR) for all cancers. METHODS: Cancer incidence and mortality data were obtained
      from NSW residents for 2004-2008 (averaged) by sex, region of birth and 10 year
      age groups. Age standardised incidence and mortality rates were calculated with
      95% confidence intervals (per 100,000), using the world standard population. In
      the place of 5-year survival rates, we used age standardised MIRs (=M/I) as a
      simple proxy indicator of cancer survival. RESULTS: All-cancer incidence only
      exceeded Australian born people (308.5) for New Zealand born (322). The highest
      reported incidence rates for cancers from all regions were prostate and breast
      cancers. All-cancer mortality exceeded Australian-born (105.3) in people born in
      Western Europe (110.9), Oceania (108.2) and UK and Ireland (106.4). For
      Australian-born residents, the MIR was 34 cancer deaths per 100 cases compared to
      residents from Central Europe at 38 deaths per 100 cases and lowest at 28 deaths
      per 100 cases for residents from Central and Southern Asia. CONCLUSION: Some
      disparities between Australian-born NSW residents and immigrants were identified
      in prostate, breast and lung cancer mortality rates. While on average most
      immigrant groups have similar cancer characteristics for the top cancers, areas
      for improvement to inform strategies to alleviate cancer disparities are
      required. This analysis suggests that NSW residents could benefit from specific
      prevention programmes on healthy eating and smoking cessation, especially people
      from Central Europe, UK and Ireland and Western Europe. Rising immigration rates
      encourage us to continue to address the areas indicated for improvement.

PMID- 26306861
TI  - Alterations in the sputum proteome and transcriptome in smokers and early-stage
      COPD subjects.
AB  - Chronic obstructive pulmonary disease (COPD) is one of the most prevalent lung
      diseases. Cigarette smoking is the main risk factor for COPD. In this parallel
      group clinical study we investigated to what extent the transitions in a chronic
      exposure-to-disease model are reflected in the proteome and cellular
      transcriptome of induced sputum samples. We selected 60 age- and gender-matched
      individuals for each of the four study groups: current asymptomatic smokers,
      smokers with early stage COPD, former smokers, and never smokers. The cell-free
      sputum supernatant was analyzed by quantitative proteomics and the cellular mRNA
      fraction by gene expression profiling. The sputum proteome of current smokers
      clearly reflected the common physiological responses to smoke exposure, including
      alterations in mucin/trefoil proteins and a prominent xenobiotic/oxidative stress
      response. The latter response also was observed in the transcriptome, which
      additionally demonstrated an immune-cell polarization change. The former smoker
      group showed nearly complete attenuation of these biological effects. Thirteen
      differentially abundant proteins between the COPD and the asymptomatic smoker
      group were identified including TIMP1, APOA1, C6orf58, and BPIFB1 (LPLUNC1). In
      summary, our study demonstrates that sputum profiling can capture the complex and
      reversible physiological response to cigarette smoke exposure, which appears to
      be only slightly modulated in early-stage COPD. 

PMID- 26306862
TI  - Proteomic analysis of flooded soybean root exposed to aluminum oxide
      nanoparticles.
AB  - Aluminum oxide (Al2O3) nanoparticles are used in agricultural products and cause
      various adverse growth effects on different plant species. To study the effects
      of Al2O3 nanoparticles on soybean under flooding stress, a gel-free proteomic
      technique was used. Morphological analysis revealed that treatment with 50 ppm
      Al2O3 nanoparticles under flooding stress enhanced soybean growth compared to ZnO
      and Ag nanoparticles. A total of 172 common proteins that significantly changed
      in abundance among control, flooding-stressed, and flooding-stressed soybean
      treated with Al2O3 nanoparticles were mainly related to energy metabolism. Under
      Al2O3 nanoparticles the energy metabolism was decreased compared to flooding
      stress. Hierarchical clustering divided identified proteins into four clusters,
      with proteins related to glycolysis exhibiting the greatest changes in abundance.
      Al2O3 nanoparticle-responsive proteins were predominantly related to protein
      synthesis/degradation, glycolysis, and lipid metabolism. mRNA expression analysis
      of Al2O3 nanoparticle-responsive proteins that displayed a 5-fold change in
      abundance revealed that NmrA-like negative transcriptional regulator was up
      regulated, and flavodoxin-like quinone reductase was down-regulated. Moreover,
      cell death in root including hypocotyl was less evident in flooding-stressed with
      Al2O3 nanoparticles compared to flooding-treated soybean. These results suggest
      that Al2O3 nanoparticles might promote the growth of soybean under flooding
      stress by regulating energy metabolism and cell death.

PMID- 26306863
TI  - Gamma Knife Radiosurgery for Pediatric Arteriovenous Malformations: A Canadian
      Experience.
AB  - BACKGROUND: Gamma Knife (GK) radiosurgery for pediatric arteriovenous
      malformations (AVM) of the brain presents a non-invasive treatment option. We
      report our institutional experience with GK for pediatric AVMs. METHODS: We
      performed a retrospective review of all pediatric patients treated with GK for
      cerebral AVMs at our institution from November 2003 up to and including September
      2014. Patient demographics, AVM characteristics, treatment parameters and AVM
      responses were recorded. RESULTS: Nineteen patients were treated, with 4 lost to
      follow-up. The mean age was 14.2 years (range. 7-18 years), with 10 being males
      (52.6%). The mean AVM diameter and volume were 2.68 cm and 3.10 cm3 respectively.
      The mean Spetzler-Martin (SM) and Pollock grades of the treated AVMs were 2.4 and
      0.99 respectively. The mean follow-up was 62 months. All AVMs treated
      demonstrated a response on follow-up imaging. Nine of 15 (60.0%) patients
      displayed obliteration of their AVMs. Nine of 11 patients with a minimum of 3
      years follow-up (81.8%) displayed obliteration, with SM and Pollock grades
      correlating to the chance of obliteration in this group. Two patients developed
      post-GK edema requiring short course dexamethasone therapy. No other major
      complications occurred. No permanent complications occurred. CONCLUSIONS: GK
      radiosurgery for pediatric AVMs offers a safe and effective treatment option,
      with low permanent complication rates during early follow-up.

PMID- 26306864
TI  - A Digital Repository and Execution Platform for Interactive Scholarly
      Publications in Neuroscience.
AB  - The CARMEN Virtual Laboratory (VL) is a cloud-based platform which allows
      neuroscientists to store, share, develop, execute, reproduce and publicise their
      work. This paper describes new functionality in the CARMEN VL: an interactive
      publications repository. This new facility allows users to link data and software
      to publications. This enables other users to examine data and software associated
      with the publication and execute the associated software within the VL using the
      same data as the authors used in the publication. The cloud-based architecture
      and SaaS (Software as a Service) framework allows vast data sets to be uploaded
      and analysed using software services. Thus, this new interactive publications
      facility allows others to build on research results through reuse. This aligns
      with recent developments by funding agencies, institutions, and publishers with a
      move to open access research. Open access provides reproducibility and
      verification of research resources and results. Publications and their associated
      data and software will be assured of long-term preservation and curation in the
      repository. Further, analysing research data and the evaluations described in
      publications frequently requires a number of execution stages many of which are
      iterative. The VL provides a scientific workflow environment to combine software
      services into a processing tree. These workflows can also be associated with
      publications and executed by users. The VL also provides a secure environment
      where users can decide the access rights for each resource to ensure copyright
      and privacy restrictions are met. 

PMID- 26306865
TI  - Quantitative Evaluation of Intensity Inhomogeneity Correction Methods for
      Structural MR Brain Images.
AB  - The correction of intensity non-uniformity (INU) in magnetic resonance (MR)
      images is extremely important to ensure both within-subject and across-subject
      reliability. Here we tackled the problem of objectively comparing INU correction
      techniques for T1-weighted images, which are the most commonly used in structural
      brain imaging. We focused our investigations on the methods integrated in widely
      used software packages for MR data analysis: FreeSurfer, BrainVoyager, SPM and
      FSL. We used simulated data to assess the INU fields reconstructed by those
      methods for controlled inhomogeneity magnitudes and noise levels. For each
      method, we evaluated a wide range of input parameters and defined an enhanced
      configuration associated with best reconstruction performance. By comparing
      enhanced and default configurations, we found that the former often provide much
      more accurate results. Accordingly, we used enhanced configurations for a more
      objective comparison between methods. For different levels of INU magnitude and
      noise, SPM and FSL, which integrate INU correction with brain segmentation,
      generally outperformed FreeSurfer and BrainVoyager, whose methods are exclusively
      dedicated to INU correction. Nonetheless, accurate INU field reconstructions can
      be obtained with FreeSurfer on images with low noise and with BrainVoyager for
      slow and smooth inhomogeneity profiles. Our study may prove helpful for an
      accurate selection of the INU correction method to be used based on the
      characteristics of actual MR data. 

PMID- 26306866
TI  - TReMAP: Automatic 3D Neuron Reconstruction Based on Tracing, Reverse Mapping and
      Assembling of 2D Projections.
AB  - Efficient and accurate digital reconstruction of neurons from large-scale 3D
      microscopic images remains a challenge in neuroscience. We propose a new
      automatic 3D neuron reconstruction algorithm, TReMAP, which utilizes 3D Virtual
      Finger (a reverse-mapping technique) to detect 3D neuron structures based on
      tracing results on 2D projection planes. Our fully automatic tracing strategy
      achieves close performance with the state-of-the-art neuron tracing algorithms,
      with the crucial advantage of efficient computation (much less memory consumption
      and parallel computation) for large-scale images. 

PMID- 26306868
TI  - Human cathepsin L, a papain-like collagenase without proline specificity.
AB  - Several members of the papain-like peptidase family have the ability to degrade
      collagen molecules by cleaving within the triple helix region of this difficult
      substrate. A common denominator of these peptidases is their ability to cleave
      substrates with Pro in the P2 position. In humans, cathepsin K is the best-known
      papain-like collagenase. Here, we investigate the collagenolytic activity of
      human cathepsin L, which is closely related to cathepsin K. We show that, despite
      lacking proline specificity, cathepsin L efficiently cleaves type I collagen
      within the triple helix region and produces a cleavage pattern similar to that of
      cathepsin K. We demonstrate that both enzymes have similar affinities for type I
      collagen and are able to release proteolytic fragments from insoluble collagen.
      Moreover, cathepsin K is only approximately fourfold more potent than cathepsin L
      in releasing fragments from reconstituted fibrils of FITC-labeled collagen.
      Replacing active site residues of cathepsin L with those from cathepsin K
      introduces cathepsin K-like specificity towards synthetic substrates and
      increases the collagenolytic activity of cathepsin L. Replacing three residues in
      the S2 subsite is sufficient to produce a mutant with collagenolytic activity on
      par with human cathepsin K. These results provide a basis for engineering
      collagenolytic activity into non-collagenolytic papain-like scaffolds. 

PMID- 26306867
TI  - The Medical Professionalism of Korean Physicians: Present and Future.
AB  - BACKGROUND: Medical professionalism is a core aspect of medical education and
      practice worldwide. Medical professionalism must be reinterpreted to adapt to
      different social/cultural/historical contexts. We conducted a survey to examine
      the current understanding and perceived value of medical professionalism among
      Korean physicians. METHODS: The survey was distributed to 950 physicians
      nationwide; 721 (75.89%) completed surveys were returned between 1 April and 31
      July 2011. RESULTS: In their practice, Korean physicians prioritized the values
      and virtues of medical professionalism in the following (descending) order:
      veracity, respect for patient autonomy, integrity, responsibility, altruism, and
      honesty. Approximately two-thirds of physicians responded that medical
      professionalism is an element of their vocation. When asked to choose the most
      important sets of attributes or virtues of medical professionalism from a
      provided list, the top three sets (in descending order of frequency) were:
      "responsibility and duty," "veracity, integrity, and honesty," and "rapport with
      patients and conversational skill." CONCLUSIONS: Korean physicians value moral
      duties, such as responsibility and veracity, more than they do moral virtues,
      such as altruism and honesty with patients. It is presumed that physicians are
      under pressure due to governmental regulation of the national healthcare system
      and have difficulty exercising their autonomy.

PMID- 26306869
TI  - Reply to the Letter to the Editor entitled "Low-dose intravenous tissue-type
      plasminogen activator for prosthetic valve thrombosis is better than standard
      dose streptokinase".

PMID- 26306870
TI  - Astrocyte-mediated metaplasticity in the hippocampus: Help or hindrance?
AB  - For over two decades it has been increasingly appreciated that synaptic
      plasticity mechanisms are subject to activity-dependent metaplastic regulation.
      In recent years it has also become apparent that astrocytes are active partners
      with neurons at synapses, and have the capability to powerfully regulate synaptic
      plasticity. However, the field of astrocyte-mediated metaplasticity is still very
      much in its infancy. Further, what contribution astrocyte-mediated metaplasticity
      makes to hippocampal dysfunction is almost entirely unknown. This contribution
      may be particularly important given that altered plasticity in the hippocampus is
      a hallmark of several disease states. The known ways by which astrocytes exert
      metaplasticity are reviewed here, and hypothetical mechanisms of astrocyte
      mediated metaplasticity are considered for the benefit of future investigation.
      The latter half of this review focuses on what part these mechanisms, and others,
      may play in the diseased or injured hippocampus, and how this might contribute to
      the altered cognition seen in several pathologies common to the hippocampus. 

PMID- 26306871
TI  - Structural imaging of hippocampal subfields in healthy aging and Alzheimer's
      disease.
AB  - Hippocampal atrophy, as evidenced using magnetic resonance imaging (MRI), is one
      of the most validated, easily accessible and widely used biomarkers of
      Alzheimer's disease (AD). However, its imperfect sensitivity and specificity have
      highlighted the need to improve the analysis of MRI data. Based on
      neuropathological data showing a differential vulnerability of hippocampal
      subfields to AD processes, neuroimaging researchers have tried to capture
      corresponding morphological changes within the hippocampus. The present review
      provides an overview of the methodological developments that allow the assessment
      of hippocampal subfield morphology in vivo, and summarizes the results of studies
      looking at the effects of AD and normal aging on these structures. Most studies
      highlighted a focal atrophy of the CA1 subfield in the early (predementia or even
      preclinical) stages of AD, before atrophy becomes more widespread at the dementia
      stage, consistent with the pathological literature. Preliminary studies have
      indicated that looking at this focal atrophy pattern rather than standard whole
      hippocampus volumetry improves diagnostic accuracy at the mild cognitive
      impairment (MCI) stage. However, controversies remain regarding changes in
      hippocampal subfield structure in normal aging and regarding correlations between
      specific subfield volume and memory abilities, very likely because of the strong
      methodological variability between studies. Overall, hippocampal subfield
      analysis has proven to be a promising technique in the study of AD. However,
      harmonization of segmentation protocols and studies on larger samples are needed
      to enable accurate comparisons between studies and to confirm the clinical
      utility of these techniques. 

PMID- 26306873
TI  - Corrigendum: Tonic endocannabinoid-mediated modulation of GABA release is
      independent of the CB1 content of axon terminals.

PMID- 26306874
TI  - SLy1 regulates T-cell proliferation during Listeria monocytogenes infection in a
      Foxo1-dependent manner.
AB  - Infection of mice with Listeria monocytogenes results in a strong T-cell response
      that is critical for an efficient defense. Here, we demonstrate that the adapter
      protein SLy1 (SH3-domain protein expressed in Lymphocytes 1) is essential for the
      generation of a fully functional T-cell response. The lack of SLy1 leads to
      reduced survival rates of infected mice. The increased susceptibility of SLy1
      knock-out (KO) mice was caused by reduced proliferation of differentiated T
      cells. Ex vivo analyses of isolated SLy1 KO T cells displayed a dysregulation of
      Forkhead box protein O1 shuttling after TCR signaling, which resulted in an
      increased expression of cell cycle inhibiting genes, and therefore, reduced
      expansion of the T-cell population. Forkhead box protein O1 shuttles to the
      cytoplasm after phosphorylation in a protein complex including 14-3-3 proteins.
      Interestingly, we observed a similar regulation for the adapter protein SLy1,
      where TCR stimulation results in SLy1 phosphorylation and SLy1 export to the
      cytoplasm. Moreover, immunoprecipitation analyses revealed a binding of SLy1 to
      14-3-3 proteins. Altogether, this study describes SLy1 as an immunoregulatory
      protein, which is involved in the generation of adaptive immune responses during
      L. monocytogenes infection, and provides a model of how SLy1 regulates T-cell
      proliferation.

PMID- 26306872
TI  - Sex differences in NMDA GluN1 plasticity in rostral ventrolateral medulla neurons
      containing corticotropin-releasing factor type 1 receptor following slow-pressor
      angiotensin II hypertension.
AB  - There are profound, yet incompletely understood, sex differences in the
      neurogenic regulation of blood pressure. Both corticotropin signaling and
      glutamate receptor plasticity, which differ between males and females, are known
      to play important roles in the neural regulation of blood pressure. However, the
      relationship between hypertension and glutamate plasticity in corticotropin
      releasing factor (CRF)-receptive neurons in brain cardiovascular regulatory
      areas, including the rostral ventrolateral medulla (RVLM) and paraventricular
      nucleus of the hypothalamus (PVN), is not understood. In the present study, we
      used dual-label immuno-electron microscopy to analyze sex differences in slow
      pressor angiotensin II (AngII) hypertension with respect to the subcellular
      distribution of the obligatory NMDA glutamate receptor subunit 1 (GluN1) subunit
      of the N-methyl-D-aspartate receptor (NMDAR) in the RVLM and PVN. Studies were
      conducted in mice expressing the enhanced green fluorescence protein (EGFP) under
      the control of the CRF type 1 receptor (CRF1) promoter (i.e., CRF1-EGFP reporter
      mice). By light microscopy, GluN1-immunoreactivity (ir) was found in CRF1-EGFP
      neurons of the RVLM and PVN. Moreover, in both regions tyrosine hydroxylase (TH)
      was found in CRF1-EGFP neurons. In response to AngII, male mice showed an
      elevation in blood pressure that was associated with an increase in the
      proportion of GluN1 on presumably functional areas of the plasma membrane (PM) in
      CRF1-EGFP dendritic profiles in the RVLM. In female mice, AngII was neither
      associated with an increase in blood pressure nor an increase in PM GluN1 in the
      RVLM. Unlike the RVLM, AngII-mediated hypertension had no effect on GluN1
      localization in CRF1-EGFP dendrites in the PVN of either male or female mice.
      These studies provide an anatomical mechanism for sex-differences in the
      convergent modulation of RVLM catecholaminergic neurons by CRF and glutamate.
      Moreover, these results suggest that sexual dimorphism in AngII-induced
      hypertension is reflected by NMDA receptor trafficking in presumptive
      sympathoexcitatory neurons in the RVLM.

PMID- 26306875
TI  - Interactive 3D-PDF Presentations for the Simulation and Quantification of
      Extended Endoscopic Endonasal Surgical Approaches.
AB  - A three-dimensional (3D) model of the skull base was reconstructed from the pre-
      and post-dissection head CT images and embedded in a Portable Document Format
      (PDF) file, which can be opened by freely available software and used offline.
      The CT images were segmented using a specific 3D software platform for biomedical
      data, and the resulting 3D geometrical models of anatomical structures were used
      for dual purpose: to simulate the extended endoscopic endonasal transsphenoidal
      approaches and to perform the quantitative analysis of the procedures. The
      analysis consisted of bone removal quantification and the calculation of
      quantitative parameters (surgical freedom and exposure area) of each procedure.
      The results are presented in three PDF documents containing JavaScript-based
      functions. The 3D-PDF files include reconstructions of the nasal structures
      (nasal septum, vomer, middle turbinates), the bony structures of the anterior
      skull base and maxillofacial region and partial reconstructions of the optic
      nerve, the hypoglossal and vidian canals and the internal carotid arteries.
      Alongside the anatomical model, axial, sagittal and coronal CT images are shown.
      Interactive 3D presentations were created to explain the surgery and the
      associated quantification methods step-by-step. The resulting 3D-PDF files allow
      the user to interact with the model through easily available software, free of
      charge and in an intuitive manner. The files are available for offline use on a
      personal computer and no previous specialized knowledge in informatics is
      required. The documents can be downloaded at http://hdl.handle.net/2445/55224 . 

PMID- 26306876
TI  - Hybrid Features and Mediods Classification based Robust Segmentation of Blood
      Vessels.
AB  - Retinal blood vessels are the source to provide oxygen and nutrition to retina
      and any change in the normal structure may lead to different retinal
      abnormalities. Automated detection of vascular structure is very important while
      designing a computer aided diagnostic system for retinal diseases. Most popular
      methods for vessel segmentation are based on matched filters and Gabor wavelets
      which give good response against blood vessels. One major drawback in these
      techniques is that they also give strong response for lesion (exudates,
      hemorrhages) boundaries which give rise to false vessels. These false vessels may
      lead to incorrect detection of vascular changes. In this paper, we propose a new
      hybrid feature set along with new classification technique for accurate detection
      of blood vessels. The main motivation is to lower the false positives especially
      from retinal images with severe disease level. A novel region based hybrid
      feature set is presented for proper discrimination between true and false
      vessels. A new modified m-mediods based classification is also presented which
      uses most discriminating features to categorize vessel regions into true and
      false vessels. The evaluation of proposed system is done thoroughly on publicly
      available databases along with a locally gathered database with images of
      advanced level of retinal diseases. The results demonstrate the validity of the
      proposed system as compared to existing state of the art techniques. 

PMID- 26306877
TI  - A Machine Learning Method for Power Prediction on the Mobile Devices.
AB  - Energy profiling and estimation have been popular areas of research in multicore
      mobile architectures. While short sequences of system calls have been recognized
      by machine learning as pattern descriptions for anomalous detection, power
      consumption of running processes with respect to system-call patterns are not
      well studied. In this paper, we propose a fuzzy neural network (FNN) for training
      and analyzing process execution behaviour with respect to series of system calls,
      parameters and their power consumptions. On the basis of the patterns of a series
      of system calls, we develop a power estimation daemon (PED) to analyze and
      predict the energy consumption of the running process. In the initial stage, PED
      categorizes sequences of system calls as functional groups and predicts their
      energy consumptions by FNN. In the operational stage, PED is applied to identify
      the predefined sequences of system calls invoked by running processes and
      estimates their energy consumption. 

PMID- 26306878
TI  - Information Architecture for Quality Management Support in Hospitals.
AB  - Quality Management occupies a strategic role in organizations, and the adoption
      of computer tools within an aligned information architecture facilitates the
      challenge of making more with less, promoting the development of a competitive
      edge and sustainability. A formal Information Architecture (IA) lends
      organizations an enhanced knowledge but, above all, favours management. This
      simplifies the reinvention of processes, the reformulation of procedures,
      bridging and the cooperation amongst the multiple actors of an organization. In
      the present investigation work we planned the IA for the Quality Management
      System (QMS) of a Hospital, which allowed us to develop and implement the
      QUALITUS (QUALITUS, name of the computer application developed to support Quality
      Management in a Hospital Unit) computer application. This solution translated
      itself in significant gains for the Hospital Unit under study, accelerating the
      quality management process and reducing the tasks, the number of documents, the
      information to be filled in and information errors, amongst others. 

PMID- 26306880
TI  - Supramolecular chemistry ... and beyond.
AB  - The research group of Jean-Marie Lehn recently celebrated its 50th anniversary.
      Lehn, who shared the Nobel Prize in Chemistry 1987 with Donald J. Cram and
      Charles J. Pedersen, has been active in many initiatives in the European chemical
      community, and was instrumental in the founding of Chemistry-A European Journal
      and ChemBioChem. This Meeting Report summarizes the symposium that was recently
      held to commemorate the achievements of the Lehn group. 

PMID- 26306879
TI  - Diversification of the ant odorant receptor gene family and positive selection on
      candidate cuticular hydrocarbon receptors.
AB  - BACKGROUND: Chemical communication plays important roles in the social behavior
      of ants making them one of the most successful groups of animals on earth.
      However, the molecular evolutionary process responsible for their chemosensory
      adaptation is still elusive. Recent advances in genomic studies have led to the
      identification of large odorant receptor (Or) gene repertoires from ant genomes
      providing fruitful materials for molecular evolution analysis. The aim of this
      study was to test the hypothesis that diversification of this gene family is
      involved in olfactory adaptation of each species. RESULTS: We annotated the Or
      genes from the genome sequences of two leaf-cutter ants, Acromyrmex echinatior
      and Atta cephalotes (385 and 376 putative functional genes, respectively). These
      were used, together with Or genes from Camponotus floridanus, Harpegnathos
      saltator, Pogonomyrmex barbatus, Linepithema humile, Cerapachys biroi, Solenopsis
      invicta and Apis mellifera, in molecular evolution analysis. Like the Or family
      in other insects, ant Or genes evolve by the birth-and-death model of gene family
      evolution. Large gene family expansions involving tandem gene duplications, and
      gene gains outnumbering losses, are observed. Codon analysis of genes in lineage
      specific expansion clades revealed signatures of positive selection on the
      candidate cuticular hydrocarbon receptor genes (9-exon subfamily) of Cerapachys
      biroi, Camponotus floridanus, Acromyrmex echinatior and Atta cephalotes.
      Positively selected amino acid positions are primarily in transmembrane domains 3
      and 6, which are hypothesized to contribute to the odor-binding pocket,
      presumably mediating changing ligand specificity. CONCLUSIONS: This study
      provides support for the hypothesis that some ant lineage-specific Or genes have
      evolved under positive selection. Newly duplicated genes particularly in the
      candidate cuticular hydrocarbon receptor clade that have evolved under positive
      selection may contribute to the highly sophisticated lineage-specific chemical
      communication in each ant species.

PMID- 26306881
TI  - Orthographic and phonological neighborhood effects in handwritten word
      perception.
AB  - In printed-word perception, the orthographic neighborhood effect (i.e., faster
      recognition of words with more neighbors) has considerable theoretical
      importance, because it implicates great interactivity in lexical access. Mulatti,
      Reynolds, and Besner Journal of Experimental Psychology: Human Perception and
      Performance, 32, 799-810 (2006) questioned the validity of orthographic
      neighborhood effects, suggesting that they reflect a confound with phonological
      neighborhood density. They reported that, when phonological density is
      controlled, orthographic neighborhood effects vanish. Conversely, phonological
      neighborhood effects were still evident even when controlling for orthographic
      neighborhood density. The present study was a replication and extension of
      Mulatti et al. (2006), with words presented in four different formats (computer
      generated print and cursive, and handwritten print and cursive). The results from
      Mulatti et al. (2006) were replicated with computer-generated stimuli, but were
      reversed with natural stimuli. These results suggest that, when ambiguity is
      introduced at the level of individual letters, top-down influences from lexical
      neighbors are increased.

PMID- 26306882
TI  - Simplifying the Welfare Quality(r) assessment protocol for broiler chicken
      welfare.
AB  - Welfare Quality((r)) (WQ) assessment protocols place the emphasis on animal-based
      measures as an indicator for animal welfare. Stakeholders, however, emphasize
      that a reduction in the time taken to complete the protocol is essential to
      improve practical applicability. We studied the potential for reduction in time
      to complete the WQ broiler assessment protocol and present some modifications to
      the protocol correcting a few errors in the original calculations. Data was used
      from 180 flocks assessed on-farm and 150 flocks assessed at the slaughter plant.
      Correlations between variables were calculated, and where correlation was
      moderate, meaningful and promising (in terms of time reduction), simplification
      was considered using one variable predicted from another variable. Correlation
      analysis revealed a promising correlation between severe hock burn and gait
      scores on-farm. Therefore, prediction of gait scores using hock burn scores was
      studied further as a possible simplification strategy (strategy 1). Measurements
      of footpad dermatitis, hock burn, cleanliness and gait score on-farm correlated
      moderately to highly with slaughter plant measurements of footpad dermatitis
      and/or hock burn, supporting substitution of on-farm measurements with slaughter
      plant data. A simplification analysis was performed using footpad dermatitis,
      hock burn, cleanliness and gait scores measured on-farm predicted from slaughter
      plant measurements of footpad dermatitis and hock burn (strategy 2).
      Simplification strategies were compared with the full assessment protocol. Close
      agreement was found between the full protocol and both simplification strategies
      although large confidence intervals were found for specificity of the simplified
      models. It is concluded that the proposed simplification strategies are
      encouraging; strategy 1 can reduce the time to complete the on-farm assessment by
      ~1 h (25% to 33% reduction) and strategy 2 can reduce on-farm assessment time by
      ~2 h (50% to 67% reduction). Both simplification strategies should, however, be
      validated further, and tested on farms with a wide distribution across the
      different welfare categories of WQ.

PMID- 26306884
TI  - Ketosis may promote brain macroautophagy by activating Sirt1 and hypoxia
      inducible factor-1.
AB  - Ketogenic diets are markedly neuroprotective, but the basis of this effect is
      still poorly understood. Recent studies demonstrate that ketone bodies increase
      neuronal levels of hypoxia-inducible factor-1alpha (HIF-1alpha), possibly owing
      to succinate-mediated inhibition of prolyl hydroxylase activity. Moreover, there
      is reason to suspect that ketones can activate Sirt1 in neurons, in part by
      increasing cytoplasmic and nuclear levels of Sirt1's obligate cofactor NAD(+).
      Another recent study has observed reduced activity of mTORC1 in the hippocampus
      of rats fed a ketogenic diet - an effect plausibly attributable to Sirt1
      activation. Increased activities of HIF-1 and Sirt1, and a decrease in mTORC1
      activity, could be expected to collaborate in the induction of neuronal
      macroautophagy. Considerable evidence points to moderate up-regulation of
      neuronal autophagy as a rational strategy for prevention of neurodegenerative
      disorders; elimination of damaged mitochondria that overproduce superoxide, as
      well as clearance of protein aggregates that mediate neurodegeneration,
      presumably contribute to this protection. Hence, autophagy may mediate some of
      the neuroprotective benefits of ketogenic diets. Brain-permeable agents which
      activate AMP-activated kinase, such as metformin and berberine, as well as the
      Sirt1 activator nicotinamide riboside, can also boost neuronal autophagy, and may
      have potential for amplifying the impact of ketogenesis on this process. Since it
      might not be practical for most people to adhere to ketogenic diets continuously,
      alternative strategies are needed to harness the brain-protective potential of
      ketone bodies. These may include ingestion of medium-chain triglycerides or
      coconut oil, intermittent ketogenic dieting, and possibly the use of supplements
      that promote hepatic ketogenesis - notably carnitine and hydroxycitrate - in
      conjunction with dietary regimens characterized by long daily episodes of fasting
      or carbohydrate avoidance. 

PMID- 26306883
TI  - LASER versus electromagnetic field in treatment of hemarthrosis in children with
      hemophilia.
AB  - Children with hemophilia usually have recurrent joint bleeding that leads to
      joint damage, loss of range of motion, and restriction of mobility, therefore
      affecting the quality of life in these children. The purpose of this study was to
      compare the effects of low-level laser therapy (LLLT) to that of pulsed
      electromagnetic field (PEMF) in treatment of hemarthrosis in children with
      hemophilia. Thirty boys with hemophilia A with ages ranging from 9 to 13 years
      were selected and assigned randomly, using sealed envelopes, into two equal
      intervention groups. The study group I received the traditional physical therapy
      program in addition to LLLT, whereas the study group II received the same
      physical therapy program given to the study group I in addition to PEMF. Both
      groups received the treatment sessions three times per week for three successive
      months. Pain, laboratory investigations, swelling, and range of motion (ROM) of
      the affected knee joint, in addition to physical fitness were evaluated before,
      at the end of the sixth week and at 12 weeks of the treatment program. Laser
      group showed significant improvement in all measured variables after the sixth
      week of treatment when compared with PEMF. By 12 weeks of treatment, there was a
      significant improvement in pain, ROM, ESR and leucocytes levels in laser group
      compared with PEMF, while there was no significant difference in knee
      circumferences and the 6-min walk test (6MWT) between both groups. Both groups
      showed significant improvement at 12 weeks of treatment compared with that at 6
      weeks. Both LLLT and PEMF are effective modalities in reducing pain, swelling,
      increasing ROM and improving physical fitness. Twelve weeks of treatment of both
      modalities demonstrated significant improvement than 6 weeks of treatment. Laser
      therapy induced significant improvement than electromagnetic therapy in treatment
      of hemarthrosis-related problems in children with hemophilia. 

PMID- 26306885
TI  - Prenatal Caloric Intake and the Development of Academic Achievement Among U.S.
      Children From Ages 5 to 14.
AB  - Few studies have examined the relation between maternal caloric intake during
      pregnancy and growth in child academic achievement while controlling for
      important confounding influences. Using data from the National Longitudinal
      Survey of Youth, the current study examined the effects of reduced prenatal
      caloric intake on growth in scores on the Peabody Individual Achievement Test
      from ages 5 to 14. While models controlling for within-family covariates showed
      that prenatal caloric intake was associated with lower reading and mathematical
      achievement at age 5, models controlling for between-family covariates (such as
      maternal IQ) and unobserved familial confounders revealed only a statistically
      significant association between siblings differentially exposed to prenatal
      caloric intake and mathematical achievement at age 5. 

PMID- 26306886
TI  - Emerging norovirus GII.17 in Taiwan.

PMID- 26306888
TI  - Two Articles: Similar, Not the Same.

PMID- 26306887
TI  - The waaL gene mutation compromised the inhabitation of Enterobacter sp. Ag1 in
      the mosquito gut environment.
AB  - BACKGROUND: The mosquito gut harbors a variety of bacteria that are dynamically
      associated with mosquitoes in various contexts. However, little is known about
      bacterial factors that affect bacterial inhabitation in the gut microbial
      community. Enterobacter sp. Ag1 is a predominant Gram negative bacterium in the
      mosquito midgut. METHODS: In a mutant library that was generated using transposon
      Tn5-mediated mutagenesis, a mutant was identified, in which the gene waaL was
      disrupted by the Tn5 insertion. The waaL encodes O antigen ligase, which is
      required for the attachment of O antigen to the outer core oligosaccharide of the
      lipopolysaccharide (LPS). RESULTS: The waaL(-) mutation caused the O antigen
      repeat missing in the LPS. The normal LPS structure was restored when the mutant
      was complemented with a plasmid containing waaL gene. The waaL(-) mutation did
      not affect bacterial proliferation in LB culture, the mutant cells grew at a rate
      the same as the wildtype (wt) cells. However, when waaL(-) strain were co
      cultured with the wt strain or complemented strain, the mutant cells proliferated
      with a slower rate, indicating that the mutants were less competitive than wt
      cells in a community setting. Similarly, in a co-feeding assay, when
      fluorescently tagged wt strain and waaL(-) strain were orally co-introduced into
      the gut of Anopheles stephensi mosquitoes, the mutant cells were less prevalent
      in both sugar-fed and blood-fed guts. The data suggest that the mutation
      compromised the bacterial inhabitation in the gut community. Besides, the mutant
      was more sensitive to oxidative stress, demonstrated by lower survival rate upon
      exposure to 20 mM H2O2. CONCLUSION: Lack of the O antigen structure in LPS of
      Enterobacter compromised the effective growth in co-culture and co-feeding
      assays. In addition, O-antigen was involved in protection against oxidative
      stress. The findings suggest that intact LPS is crucial for the bacteria to
      steadily stay in the gut microbial community.

PMID- 26306889
TI  - Extensive Necrotising Enterocolitis: Objective Evaluation of the Role of Second
      Look Laparotomy in Bowel Salvage and Survival.
AB  - AIM: We investigated the role and outcome of a planned second-look laparotomy
      (SLL) in preserving bowel in extensive necrotizing enterocolitis (NEC). METHODS:
      Extensive NECs managed surgically in a tertiary centre in 2006-2009 were
      retrospectively studied to include patients planned for an SLL. End points were
      bowel salvage rate and survival outcomes. Results were median (ranges), and
      statistical significance was P < 0.05. MAIN RESULTS: In 4 years, 34 NECs required
      a laparotomy, and 9 extensive NECs who required an SLL were included. The
      gestation at birth was 27 (24-38) weeks, birth weight was 1120 (580-2835) g, and
      first laparotomy performed on day 34 (2-77) of life, with SLL performed 2 (1-3)
      days after initial laparotomy. Commonest indications for SLL were doubtful bowel
      viability and physiological instability. 3 died before SLL. Patients who survived
      to have an SLL (n = 6) had remaining small bowel length of 41 (25-70) cm, overall
      small bowel salvage rate 51 % (0-100 %), and 30-day survival 5/6 (83 %). Four
      patients survived for 1 year, their length of NICU stay was 114 (76-120)
      postoperative days, time on PN was 84 postoperative days (71 days-17 months),
      including one patient with short bowel syndrome who achieved enteral autonomy at
      17 months; one late mortality had short bowel syndrome after further bowel
      resection for bowel obstruction, developed intestinal failure associated liver
      disease, and died before 1 year of life following liver transplant. CONCLUSION:
      SLL is a viable approach for extensive NEC. It offered bowel salvage rate of 51 %
      and long-term PN-free survival of 44 %, in the patient group who would have had
      significant risk of mortality and major morbidity.

PMID- 26306891
TI  - A Randomised Assessment of Trainee Doctors' Understanding and Interpretation of
      Diagnostic Test Results.
AB  - INTRODUCTION: Doctors are unfamiliar with diagnostic accuracy parameters despite
      routine clinical use of diagnostic tests to estimate disease probability.
      METHODS: Trainee doctors completed a questionnaire exploring their understanding
      of diagnostic accuracy parameters; ability to calculate post-test probability of
      a common surgical condition (appendicitis) and their perceptions on training in
      this area. To determine whether the method of information provision altered
      interpretation, trainees were randomised to receive diagnostic test information
      in three ways: positive test only; positive test with specificity and
      sensitivity; positive test with positive likelihood ratio in layman terms.
      RESULTS: 326 candidates were recruited across 30 training sessions. Trainees
      scored a median of three out of seven in questions concerning knowledge of
      diagnostic accuracy parameters. This was affected neither by training level (P =
      0.737) nor by experience in acute general surgery (P = 0.738). 30 (11.8%)
      candidates correctly estimated post-test probability; with 86.6% overestimating
      this value. Neither level of training (P = 0.180) nor experience (P = 0.242)
      influenced the accuracy of the estimate. Provision of the ultrasound scan results
      in different ways was not associated with likelihood of a correct response (P =
      0.857). CONCLUSION: This study highlights the deficiencies in trainee doctors'
      understanding and application of diagnostic tests results. Most trainees over
      estimated disease probability, increasing the risk of unnecessary intervention
      and treatment.

PMID- 26306890
TI  - Clinical Significance of Multiple Pulmonary Metastasectomy for Hepatocellular
      Carcinoma.
AB  - BACKGROUND: The lung is the most common site of extrahepatic metastasis from
      hepatocellular carcinoma (HCC). The aim of this study was to evaluate the
      significance and long-term outcomes of pulmonary metastasectomy for HCC,
      especially in patients with multiple nodules or repeated pulmonary recurrence.
      METHODS: We retrospectively analyzed 19 patients who underwent pulmonary
      metastasectomy for HCC at our institution from 1993 to 2013. RESULTS: No in
      hospital mortality occurred. The 19 patients included 14 men. The median age was
      61 (range 20-76) years. Eight patients (42 %) had single pulmonary metastatic
      lesions, whereas 4 (21 %) had >10 lesions. Median follow-up after pulmonary
      metastasectomy was 23.1 (6.3-230) months. Twelve patients died, and the cause of
      death was HCC progression in nine. The 1-, 3-, 5-, and 10-year overall survival
      rates after pulmonary metastasectomy were 89, 48, 48, and 21 %, respectively.
      Seven patients developed pulmonary recurrence after initial pulmonary
      metastasectomy. Five of the seven underwent repeat metastasectomy, with a median
      survival time of 65 months, and 2- and 3-year survival rates of 100 and 67 %,
      respectively. The 2- and 3-year survival rates in the four patients with >10
      pulmonary nodules were 75 and 50 %, respectively. CONCLUSIONS: Surgical resection
      is a safe and effective treatment in selected patients with pulmonary metastasis
      from HCC, even in those with multiple nodules. Repeated locoregional therapy for
      lung recurrence might help to improve survival in these patients.

PMID- 26306892
TI  - Evaluating the Incidence, Cause, and Risk Factors for Unplanned 30-Day
      Readmission and Emergency Department/General Practitioner Visit After Short-Stay
      Thyroidectomy.
AB  - BACKGROUND: Unplanned 30-day readmission and emergency department (ED)/general
      practitioner (GP) visit after thyroidectomy are important healthcare quality
      measures and may reduce any cost savings from performing it as a short-stay (<24
      h admission) procedure. Our study aimed to examine the incidence, cause, and risk
      factors for unplanned 30-day readmissions and ED/GP visits together following
      short-stay thyroidectomy. METHODS: One-thousand and four patients who underwent
      short-stay thyroidectomy were reviewed. A territory-wide electronic medical
      record system was used to capture all unplanned readmissions and ED/GP visits
      within 30 days of thyroidectomy. Actual date and reason for readmission or ED/GP
      visit were recorded. Other preoperative and perioperative variables were
      collected prospectively. RESULTS: Of the 80 (8.0 %) unplanned readmissions and
      ED/GP visits, 38 (47.5 %) were readmissions and 42 (52.5 %) were ED/GP visits
      only. The three most common causes of unplanned readmission and ED/GP visit were
      symptomatic hypocalcemia (n = 20, 25.0 %), upper respiratory symptoms (n = 15,
      18.8 %), and wound complaints (n = 8, 10.0 %). However, in the multivariate
      analysis, only American Society of Anesthesiologists (ASA) class III (beta
      coefficient = 0.981, odds ratio 2.586 (95 % CI 1.353-4.943), p = 0.004) and renal
      insufficiency (RI) (beta coefficient = 1.062, odds ratio 2.892 (95 % CI 1.109
      7.544), p = 0.030) were independent risk factors for unplanned 30-day readmission
      and ED/GP visit. CONCLUSION: The overall incidence of unplanned 30-day ED/GP
      visit after thyroidectomy was 8.0 % with approximately half requiring
      readmission. The most common cause for unplanned ED/GP visit was symptomatic
      hypocalcemia (25.0 %), and it was attributed to patient non-compliance to
      prescribed supplements. ASA class III and RI were significant independent risk
      factors for unplanned 30-day readmission and ED/GP visit.

PMID- 26306893
TI  - Clinical Impact of Anatomical Liver Resection for Hepatocellular Carcinoma with
      Pathologically Proven Portal Vein Invasion.
AB  - BACKGROUND: Portal vein invasion (PVI) is known to be a poor prognostic factor
      for hepatocellular carcinoma (HCC) patients. Anatomical liver resection (ALR) is
      a preferable procedure for treating HCC. However, the effect of ALR for HCC with
      PVI has not been fully evaluated. The aim of this study is to investigate the
      survival benefit of ALR for HCC patients with or without pathologically proven
      portal vein invasion (pPVI). METHODS: Curative hepatic resection was performed
      for a single HCC in 313 patients. The patients were divided into two groups
      according to the absence or presence of pPVI (absence: n = 216, presence: n =
      97). These groups were then subclassified by the surgical procedures employed
      (ALR or non-ALR), and the clinical characteristics and stratified prognoses were
      compared according to the surgical procedure between the subgroups. Uni- and
      multivariate analyses were performed to explore the significant prognostic
      factors. RESULTS: Among the patients without pPVI, there was no significant
      difference in postoperative survival between the groups. However, among the
      patients with pPVI, both the 5-year overall and recurrence-free survival rates in
      the ALR group were significantly higher than those in the non-ALR group (46.1 %
      vs. 16.3 %; p = 0.0019 and 33.8 % vs. 0 %; p = 0.0010). Multivariate analyses
      revealed that tumor differentiation and intraoperative blood loss (IOB) were
      associated with postoperative survival in patients without pPVI. On the other
      hand, in patients with pPVI, ALR, serum AFP level, and IOB were associated with
      postoperative survival. CONCLUSION: ALR confers a survival benefit for HCC
      patients with pPVI.

PMID- 26306894
TI  - Albuminuria in Hypertensive Patients: Where the Choice of Antihypertensive
      Medications Matters:: Commentary on "Several Conventional Risk Markers Suggesting
      Presence of Albuminuria Are Weak Among Rural Africans With Hypertension".

PMID- 26306895
TI  - Postpartum Breastfeeding Promotion and Duration of Exclusive Breastfeeding in
      Western Nepal.
AB  - BACKGROUND: Encouragement and skills provided to mothers during the postpartum
      period have been found to be successful in increasing exclusive breastfeeding
      rates. However, evidence from developing countries is limited. This study aimed
      to ascertain whether education and skill support provided by health workers
      during the postpartum period were associated with increased duration of exclusive
      breastfeeding in Western Nepal. METHODS: A community-based prospective cohort
      study was conducted between January and October 2014, in the Rupandehi district
      of Nepal. Information on breastfeeding promotion provided by health workers after
      birth was collected from 649 mothers. The association between breastfeeding
      promotion and exclusive breastfeeding was investigated using multivariable Cox
      regression analysis. RESULTS: Of the 649 mothers, 35 percent received all eight
      types of breastfeeding promotion advice, and 60 percent received six or more such
      types of advice. Breastfeeding promotion, such as "breastfeeding on demand"
      (hazard ratio [HR] 0.74 [95% CI 0.59-0.92]) and "not to provide pacifier or
      teats" (HR 0.82 [95% CI 0.68-0.97]), were significantly associated with a lower
      risk of exclusive breastfeeding cessation. The dose-response relationship was
      also significant for the number of advices received (HR 0.94 [95% CI 0.90-0.97]).
      CONCLUSIONS: This study provides evidence that breastfeeding education and
      support immediately after childbirth could increase the duration of
      breastfeeding. The results suggest further attention to breastfeeding promotion
      in all maternity hospitals and birthing centers through skilled birth attendants.

PMID- 26306896
TI  - Single posterior approach for circumferential decompression and anterior
      reconstruction using cervical trabecular metal mesh cage in patients with
      metastatic spinal tumour.
AB  - BACKGROUND: The goal of surgical management of metastatic spinal tumours is to
      remove the tumour mass, restore spinal stability and alignment, and provide a
      better quality of life. A single posterior transpedicular approach, with
      circumferential decompression, for anterior reconstruction has been advocated to
      reduce the risk of complication and morbidity associated with a combined anterior
      posterior approach. The purpose of our study was to evaluate the clinical
      outcomes of patients who underwent a single posterior approach for anterior
      reconstruction at our institution to determine the feasibility and effectiveness
      of the approach, including the use of a cervical trabecular metal (TM) mesh cage
      as a vertebral body replacer. As a secondary aim, we evaluated the effect of
      accumulated experience with the surgical approach on clinical outcomes. METHODS:
      Twenty consecutive cases of single posterior approach were identified from a
      retrospective review of spinal surgeries performed at our institution between
      January 2009 and December 2012. Information on the following clinical outcomes
      was retrieved from the medical charts for analysis: visual analogue pain score
      (VAS); neurological status, classified on the Frankel scale; vertebral body
      reconstruction; spinal alignment, using Cobb's angle; operative time; volume of
      blood loss; complications; and the modified Brodsky criteria score, which was
      used to classify functional recovery as excellent, good, fair, or poor. RESULTS:
      Pre- to post-surgical evaluation of outcomes demonstrated a significant decrease
      in pain (p < 0.001), improved spinal alignment, with a mean correction angle of
      12 degrees  (range, 3 degrees -29 degrees ), and higher Frankel score (p <
      0.001). No severe complications were identified, including deep surgical
      infection or neurologic deterioration. Eighteen patients achieved good to
      excellent outcomes, based on the modified Brodsky criteria (p < 0.001), with two
      patients dying within 9 and 11 months of their surgery. Accumulated surgical
      experience reduced operative time and intraoperative blood loss (p <= 0.007).
      CONCLUSIONS: A single posterior approach provided good to excellent clinical and
      functional outcomes. Based on this evidence, we propose that a posterior approach
      provides a feasible alternative to the combined posterior-anterior approach for
      managing patients with metastatic spinal tumours.

PMID- 26306897
TI  - Prenatal ultrasound evaluation of segmental level of neurological lesion in
      fetuses with myelomeningocele: development of a new technique.
AB  - OBJECTIVES: To report our preliminary experience in the use of prenatal
      ultrasound examination to assess lower-limb movements in fetuses with
      myelomeningocele. We aimed to determine the accuracy of this method to establish
      the segmental level of neurological lesion, as this is the best known predictor
      of the future ability to walk. METHODS: This was a preliminary, observational
      study including fetuses with myelomeningocele operated on prenatally. The
      patterns of movements present and absent in the affected fetuses' lower limbs
      were evaluated systematically by ultrasound examination. According to the known
      nerve function associated with each muscle group, the segmental level of
      neurological lesion was established before birth. The agreement for the segmental
      levels assigned, between the prenatal ultrasound technique and the classical
      neurological clinical examination after birth (gold standard), was tested using
      the weighed kappa (wkappa) index. RESULTS: Seventy-one fetuses with
      myelomeningocele were evaluated at the Hospital Universitari Vall d'Hebron. After
      counseling, the parents opted for prenatal surgery (26 cases), termination of
      pregnancy (43 cases) or postnatal repair (two cases). Five patients did not
      fulfil the inclusion criteria for prenatal surgery and three were excluded after
      birth. In the 18 fetuses that underwent surgery and were analyzed, the agreement
      between prenatal and postnatal segmental levels assigned was 91.7% for the right
      limb (wkappa = 0.80) and 88.9% for the left limb (wkappa = 0.73). CONCLUSIONS:
      The agreement found between prenatal and postnatal assignment of level of lesion
      in this preliminary study suggests that neurological sonographic evaluation is
      feasible before birth. This may provide accurate individualized information about
      the motor function and future ambulation prognosis of fetuses with
      myelomeningocele.

PMID- 26306898
TI  - Hesperetin Modifies the Composition of Fecal Microbiota and Increases Cecal
      Levels of Short-Chain Fatty Acids in Rats.
AB  - There has been particular interest in the prebiotic-like effects of commonly
      consumed polyphenols. This study aimed to evaluate the effects of hesperidin (HD)
      and its aglycone hesperetin (HT), major flavonoids in citrus fruits, on the
      structure and activity of gut microbiota in rats. Rats ingested an assigned diet
      (a control diet, a 0.5% HT diet, or a 1.0% HD diet) for 3 weeks. Terminal
      restriction fragment length polymorphism analysis revealed that the proportion of
      Clostridium subcluster XIVa in the feces collected at the third week of feeding
      was significantly reduced by the HT diet: 19.8 +/- 4.3% for the control diet
      versus 5.3 +/- 1.5% for the HT diet (P < 0.01). There was a significant
      difference in the cecal pool of short-chain fatty acids (SCFA), the sum of
      acetic, propionic, and butyric acids, between the control diet (212 +/- 71 MUmol)
      and the HT diet (310 +/- 51 MUmol) (P < 0.05), whereas the HD diet exhibited no
      effects (245 +/- 51 MUmol). Interestingly, dietary HT resulted in a significant
      increase in the excretion of starch in the feces. HT, but not HD, might reduce
      starch digestion, and parts of undigested starch were utilized to produce SCFA by
      microbial fermentation in the large intestine. 

PMID- 26306899
TI  - Morphological change of CD4(+) T cell during contact with DC modulates T-cell
      activation by accumulation of F-actin in the immunology synapse.
AB  - BACKGROUND: The changes in T-cell morphology during immunological synapse (IS)
      formation are essential for T-cell activation. Previous researches have shown
      that T cell changed from spherical to elongated and/or flattened during in
      contact with B cell. As most powerful antigen presenting cell, dendritic cell
      (DC) has a strong ability to activate T cells. However, the morphological change
      of T cell which contacts DC and the relationship between morphological change and
      T-cell activation are not very clear. Thus, we studied the morphological change
      of CD4(+) T cell during contact with DC. RESULTS: Using live-cell imaging, we
      discovered diversity in the T-cell morphological changes during contact with DCs.
      The elongation-flattening of CD4(+) T cells correlated with a low-level Ca(2+)
      response and a loss of T-cell receptor (TCR) signalling molecules in the IS,
      including zeta-chain associated protein kinase 70 (ZAP-70), phospholipase C-gamma
      (PLC-gamma) and protein kinase C-theta (PKC-theta), whereas rounding-flattening
      correlated with sufficient CD4(+) T-cell activation. Different morphological
      changes were correlated with the different amount of accumulated filamentous
      actin (F-actin) in the IS. Disruption of F-actin by cytochalasin D impaired the
      morphological change and the localisation of calcium microdomains in the IS and
      decreased the calcium response in CD4(+) T cells. CONCLUSION: Our study
      discovered the diversity in morphological change of T cells during contacted with
      DCs. During this process, the different morphological changes of T cells modulate
      T-cell activation by the different amount of F-actin accumulation in the IS,
      which controls the distribution of calcium microdomains to affect T-cell
      activation.

PMID- 26306900
TI  - Primary Cutaneous B-Cell Lymphoma: Management and Patterns of Recurrence at the
      Multimodality Cutaneous Lymphoma Clinic of The Ohio State University.
AB  - BACKGROUND: The increasing incidence of primary cutaneous B-cell lymphomas
      (PCBCLs) presents new challenges for clinicians. Despite advances in the clinical
      and pathologic characterization of PCBCL, the significance of the current staging
      approach as a risk profiling tool and the effect of various treatments on outcome
      remain unclear. MATERIALS AND METHODS: We retrospectively reviewed patients who
      presented with a diagnosis of PCBCL seen at The Ohio State University between
      1998 and 2012. We reviewed the initial presentation and treatment modality. We
      then assessed whether the treatment modality (conservative skin-directed vs.
      definitive radiation with or without systemic therapy), stage (T1 or >=T2), or
      histologic subtype (primary cutaneous follicle center lymphoma [PCFCL] vs.
      primary cutaneous marginal zone B-cell lymphoma [PCMZL]) affected the risk of
      recurrence. RESULTS: We identified 67 patients referred with an initial diagnosis
      of PCBCL. After imaging, 12 did not meet the criteria for PCBCL and were
      classified as having systemic B-cell lymphoma with cutaneous involvement. The
      remaining 55 patients included 25 with PCMZL, 24 with PCFCL, 2 with primary
      cutaneous large B-cell lymphoma leg type, and 4 with unclassifiable disease.
      According to the International Society of Cutaneous Lymphoma-European
      Organization for Research and Treatment of Cancer staging, 30 cases were T1
      (55%), 14 T2 (25%), and 11 T3 (20%). Comparing the time to first recurrence (TFR)
      by indolent PCBCL subtypes, we found no difference in the recurrence risk for
      either stage (T1, p = .51 vs. T2/T3, p = .30). Comparing TFR by treatment
      modality, we found no difference in TFR within T1 patients (p = .34) or T2/T3
      patients (p = .44). CONCLUSION: Our limited analysis highlights the importance of
      complete staging at diagnosis and suggests that the treatment modality does not
      affect the risk of recurrence in T1 indolent PCBCL.

PMID- 26306901
TI  - Hypertension and Circulating Cytokines and Angiogenic Factors in Patients With
      Advanced Non-Clear Cell Renal Cell Carcinoma Treated With Sunitinib: Results From
      a Phase II Trial.
AB  - BACKGROUND: We evaluated the significance of hypertension developing during
      vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor
      (VEGFR-TKI) treatment and a group of cytokines and angiogenic factors (CAFs) in
      advanced non-clear cell renal cell carcinoma (nccRCC) patients treated with
      sunitinib in a phase II study. MATERIALS AND METHODS: Using multiplex assays, we
      analyzed the levels of 38 CAFs in plasma at baseline and after 4 weeks of
      sunitinib therapy. Sunitinib benefit was defined as a partial response or stable
      disease using the Response Evaluation Criteria in Solid Tumors lasting >=4
      months. Cox proportional hazards regression models were used to assess the
      associations among hypertension, CAFs, and progression-free (PFS) and overall
      survival (OS). RESULTS: Fifty-seven patients were evaluable; 53 had baseline CAF
      levels available. The median PFS and OS were 2.9 months (95% confidence interval
      [CI], 1.4-5.5) and 16.8 months (95% CI, 10.7-27.4), respectively. Sunitinib
      benefit was observed in 21 patients (37%). However, 33 patients (60%) developed
      hypertension during treatment, although no association was found with survival or
      response. Elevated baseline soluble tumor necrosis factor (TNF) receptor I,
      interleukin-8, growth-regulated oncogene, transforming growth factor-alpha, and
      VEGFR-2 levels were associated with an increased risk of death on multivariate
      analysis. CONCLUSION: We found no association between the development of
      hypertension and survival or sunitinib benefit in advanced nccRCC. TNF and
      angiogenic/immunomodulatory mediators were identified for evaluation as markers
      of prognosis and VEGFR-TKI benefit in future studies.

PMID- 26306902
TI  - Randomized Phase II Trial of Erlotinib Beyond Progression in Advanced Erlotinib
      Responsive Non-Small Cell Lung Cancer.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor
      (TKI) therapy is clearly beneficial in patients with advanced EGFR-mutated non
      small cell lung cancer (NSCLC). However, acquired resistance develops uniformly
      and the benefit of continuation of EGFR TKI therapy beyond progression remains
      unclear. MATERIALS AND METHODS: This was a randomized phase II study of
      chemotherapy (arm A: pemetrexed or docetaxel) versus chemotherapy plus erlotinib
      (ERL) (arm B) in patients with progressive NSCLC following clinical benefit from
      erlotinib. In arm B, chemotherapy was given with erlotinib at an oral daily dose
      of 150 mg on days 2-19 of each cycle to minimize negative pharmacodynamic
      interactions. The primary endpoint was that continuation of erlotinib in this
      patient population could extend progression-free survival (PFS) by 50%. RESULTS:
      A total of 46 patients were randomized (arm A: 24; arm B: 22). Patient
      characteristics were well balanced except there were more female patients in arm
      A (p = .075). The median PFS of patients in arm A was 5.5 months and for those in
      arm B, 4.4 months (p = .699). The response rates were 13% and 16% in arms A and
      B, respectively (p = .79). EGFR status data were available for 39 of the 46
      patients and no significant difference in PFS was seen for continuing ERL beyond
      progression in mutation-positive patients. Substantially more toxicity was seen
      in arm B than arm A. CONCLUSION: There was added toxicity but no benefit with the
      continuation of ERL beyond progression along with chemotherapy as compared with
      chemotherapy alone. IMPLICATIONS FOR PRACTICE: The benefits of continuing
      erlotinib upon progression alongside conventional chemotherapy are unclear. This
      randomized phase II study, initiated prior to the establishment of routine
      epidermal growth factor receptor (EGFR) mutation testing, addressed this
      clinically relevant issue through randomizing patients with prior clinical
      benefit from erlotinib (thereby enriching for EGFR-mutated tumors) upon
      progression in the second- or third-line setting to conventional chemotherapy
      (single-agent pemetrexed or docetaxel) with or without continued erlotinib. The
      results showed no benefit to continuing erlotinib beyond progression, while
      significantly more side effects were noted in the combination arm. Along with
      other recently presented study findings, these results argue against the routine
      practice of continuing erlotinib in this setting.

PMID- 26306903
TI  - Targeting the WNT Signaling Pathway in Cancer Therapeutics.
AB  - The WNT signaling cascade is integral in numerous biological processes including
      embryonic development, cell cycle regulation, inflammation, and cancer.
      Hyperactivation of WNT signaling secondary to alterations to varying nodes of the
      pathway have been identified in multiple tumor types. These alterations converge
      into increased tumorigenicity, sustained proliferation, and enhanced metastatic
      potential. This review seeks to evaluate the evidence supporting the WNT pathway
      in cancer, the therapeutic strategies in modulating this pathway, and potential
      challenges in drug development.

PMID- 26306904
TI  - Challenges in the Diagnosis and Management of Well-Differentiated Neuroendocrine
      Tumors of the Lung (Typical and Atypical Carcinoid): Current Status and Future
      Considerations.
AB  - Neuroendocrine tumors (NET) of the lung represent approximately 25% of all
      primary lung tumors and can be classified as low grade (typical carcinoids),
      intermediate grade (atypical carcinoids), or high grade (large cell
      neuroendocrine carcinoma or small cell lung carcinoma). Low- and intermediate
      grade lung NET are increasingly recognized as biologically distinct from high
      grade lung NET based on clinical behavior and underlying molecular abnormalities.
      This review summarizes current knowledge and challenges in the diagnosis and
      management of low- and intermediate-grade lung NET. Accurate histopathologic
      classification of lung NET is critical to determining appropriate treatment
      options but can be challenging even for experts. For low- and intermediate-grade
      lung NET, surgery remains the mainstay of treatment for localized disease.
      Although no standard systemic therapy has been established for the treatment of
      advanced, unresectable disease, a number of promising treatment options are
      emerging, including somatostatin analogs, temozolomide-based chemotherapy,
      targeted therapy with mammalian target of rapamycin or vascular endothelial
      growth factor inhibitors, and peptide receptor radionuclide therapy. Given the
      difficulty in accurately diagnosing these tumors, and the paucity of data
      supporting establishment of standard systemic therapy options, management of
      patients within the setting of a multidisciplinary team, including specialists
      with expertise in NET, is recommended. Ongoing and future clinical trials
      hopefully will provide stronger evidence to support treatment recommendations for
      low- and intermediate-grade lung NET.

PMID- 26306905
TI  - Lysophosphatidic acid generation by pulmonary NKT cell ENPP-2/autotaxin
      exacerbates hyperoxic lung injury.
AB  - Hyperoxia is still broadly used in clinical practice in order to assure organ
      oxygenation in critically ill patients, albeit known toxic effects. In this
      present study, we hypothesize that lysophosphatidic acid (LPA) mediates NKT cell
      activation in a mouse model of hyperoxic lung injury. In vitro, pulmonary NKT
      cells were exposed to hyperoxia for 72 h, and the induction of the ectonucleotide
      pyrophosphatase/phosphodiesterase 2 (ENPP-2) was examined and production of
      lysophosphatidic acid (LPA) was measured. In vivo, animals were exposed to 100 %
      oxygen for 72 h and lungs and serum were harvested. Pulmonary NKT cells were then
      incubated with the LPA antagonist Brp-LPA. Animals received BrP-LPA prior to
      oxygen exposure. Autotaxin (ATX, ENPP-2) was significantly up-regulated on
      pulmonary NKT cells after hyperoxia (p < 0.01) in vitro. LPA levels were
      increased in supernatants of hyperoxia-exposed pulmonary NKT cells. LPA levels
      were significantly reduced by incubating NKT cells with LPA-BrP during oxygen
      exposure (p < 0,05) in vitro. Hyperoxia-exposed animals showed significantly
      increased serum levels of LPA (p <= 0,05) as well as increased pulmonary NKT cell
      numbers in vivo. BrP-LPA injection significantly improved survival as well as
      significantly decreased lung injury and lowered pulmonary NKT cell numbers. We
      conclude that NKT cell-induced hyperoxic lung injury is mediated by pro
      inflammatory LPA generation, at least in part, secondary to ENPP-2 up-regulation
      on pulmonary NKT cells. Being a potent LPA antagonist, BrP-LPA prevents hyperoxia
      induced lung injury in vitro and in vivo.

PMID- 26306906
TI  - Long noncoding RNA FER1L4 suppresses cancer cell growth by acting as a competing
      endogenous RNA and regulating PTEN expression.
AB  - Aberrantly expressed long noncoding RNAs (lncRNAs) are associated with various
      cancers. However, the roles of lncRNAs in the pathogenesis of most cancers are
      unclear. Here, we report that the lncRNA FER1L4 (fer-1-like family member 4,
      pseudogene) acts as a competing endogenous RNA (ceRNA) to regulate the expression
      of PTEN (a well-known tumor suppressor gene) by taking up miR-106a-5p in gastric
      cancer. We observed that FER1L4 was downregulated in gastric cancer and that its
      level corresponded with that of PTEN mRNA. Both FER1L4 and PTEN mRNA were targets
      of miR-106a-5p. Further experiments demonstrated that FER1L4 downregulation
      liberates miR-106a-5p and decreases the abundances of PTEN mRNA and protein. More
      importantly, FER1L4 downregulation accelerated cell proliferation by promoting
      the G0/G1 to S phase transition. We conclude that one mechanism by which lncRNAs
      function in in tumorigenesis is as ceRNAs for tumor suppressor mRNAs. 

PMID- 26306907
TI  - Immune Responses to Intestinal Microbes in Inflammatory Bowel Diseases.
AB  - Inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative
      colitis, are characterized by chronic, T-cell-mediated inflammation of the
      gastrointestinal tract that can cause significant, lifelong morbidity. Data from
      both human and animal studies indicate that IBDs are likely caused by
      dysregulated immune responses to resident intestinal microbes. Certain products
      from mycobacteria, fungi, and Clostridia stimulate increased effector T cell
      responses during intestinal inflammation, whereas other bacterial products from
      Clostridia and Bacteroides promote anti-inflammatory regulatory T cell responses.
      Antibody responses to bacterial and fungal components may help predict the
      severity of IBDs. While most currently approved treatments for IBDs generally
      suppress the patient's immune system, our growing understanding of microbial
      influences in IBDs will likely lead to the development of new diagnostic tools
      and therapies that target the intestinal microbiota. 

PMID- 26306909
TI  - Does the Volume of Post-Acute Care Affect Quality of Life in Nursing Homes?
AB  - Although short-stay, post-acute nursing home stays are increasing, little is
      known about the impact of volume of post-acute care on quality of life (QOL)
      within nursing homes. We analyzed data from the 2010 Minnesota QOL and Consumer
      Satisfaction survey ( N = 13,433 residents within 377 facilities) and federal
      Minimum Data Set to determine the influence of living in a facility with an above
      average proportion of post-acute care residents on six domains of resident QOL.
      In bivariate analyses, an above-average proportion of Medicare-funded post-acute
      care had a significant negative influence on four domains (mood, environment,
      food, engagement) and overall facility QOL. However, when resident and facility
      covariates were added to the model, only the food domain remained significant.
      Although the challenges of caring for residents with a diverse set of treatment
      and caregiving goals may negatively affect overall facility QOL, negative impacts
      are moderated by individual resident and nursing home characteristics.

PMID- 26306908
TI  - The effects of percutaneous ethanol injection followed by 20-kHz ultrasound and
      microbubbles on rabbit hepatic tumors.
AB  - OBJECTIVE: Low-frequency ultrasound (US) in combination with microbubbles (MBs)
      is able to inhibit the growth of VX2 rabbit liver tumors. In this study, we
      investigated the feasibility of using percutaneous ethanol injection (PEI)
      followed by low-frequency ultrasound and microbubbles (USMB) to inhibit VX2 tumor
      growth. METHODS: Eighteen New Zealand rabbits with hepatic VX2 tumors were
      divided into three groups: PEI, low-frequency ultrasound and MBs followed by PEI
      (USMB + PEI), and PEI followed by USMB (PEI + USMB). PEI was performed by
      ultrasound-guided injection of 95% anhydrous alcohol into internal liver tumors
      in rabbits twice a week for 2 weeks. The US parameters were 20 kHz, 2 W/cm(2),
      40% duty cycle, 5 min, and once every other day for 2 weeks. Magnetic resonance
      imaging (MRI) was used to observe tumors before and after treatment, to examine
      changes in the tumors, and to measure the diameters of the tumors. All animals
      were followed up for 180 days after tumor implantation. Autopsy was performed at
      the end of the scheduled follow-up or immediately after death. Anatomically
      observed metastatic sites included the liver, lung, abdomen, and pelvic cavity.
      The survival time of all rabbits was recorded. RESULTS: After 4 weeks of
      treatment, on MRI, the tumor diameters in the PEI, USMB + PEI, and PEI + USMB
      groups were 8.33 +/- 1.83, 19 +/- 2.61, and 4.5 +/- 1.22 mm, respectively. There
      was a significant difference in tumor size indicated by MRI in the three groups.
      Tumor size was smaller in the PEI + USMB group than in the PEI and USMB + PEI
      groups, with t = 4.54, p = 0.0062, and t = 16.38, p < .0001, respectively. The
      PEI + USMB group showed the fewest metastasis sites (chi(2) = 11.7333, p =
      0.0194) and the longest survival period (chi(2) = 7.448, p = 0.0241). CONCLUSION:
      Percutaneous ethanol injection followed by low-frequency ultrasound and
      microbubbles can be effective in inhibiting rabbit liver tumors and prolonging
      survival time.

PMID- 26306910
TI  - Erratum to: The diagnostic challenge of pulmonary tumour thrombotic
      microangiopathy as a presentation for metastatic gastric cancer: A case report
      and review of the literature.

PMID- 26306911
TI  - Detecting the vulnerable plaque in patients.
AB  - Atherosclerosis is a systemic condition that eventually evolves into vulnerable
      plaques and cardiovascular events. Pathology studies reveal that rupture-prone
      atherosclerotic plaques have a distinct morphology, namely a thin, inflamed
      fibrous cap covering a large lipidic and necrotic core. With the fast development
      of imaging techniques in the last decades, detecting vulnerable plaques thereby
      identifying individuals at high risk for cardiovascular events has become of
      major interest. Yet, in current clinical practice, there is no routine use of any
      vascular imaging modality to assess plaque characteristics as each unique
      technique has its pros and cons. This review describes the techniques that may
      evolve into screening tool for the detection of the vulnerable plaque. Finally,
      it seems that plaque morphology has been changing in the last decades leading to
      a higher prevalence of 'stable' atherosclerotic plaques, possibly due to the
      implementation of primary prevention strategies or other approaches. Therefore,
      the nomenclature of vulnerable plaque lesions should be very carefully defined in
      all studies. 

PMID- 26306912
TI  - Harmonization of the quantitative determination of volatile fatty acids profile
      in aqueous matrix samples by direct injection using gas chromatography and high
      performance liquid chromatography techniques: Multi-laboratory validation study.
AB  - The performance parameters of volatile fatty acids (VFAs) measurements were
      assessed for the first time by a multi-laboratory validation study among 13
      laboratories. Two chromatographic techniques (GC and HPLC) and two quantification
      methods such as external and internal standard (ESTD/ISTD) were combined in three
      different methodologies GC/ESTD, HPLC/ESTD and GC/ISTD. Linearity evaluation of
      the calibration functions in a wide concentration range (10-1000mg/L) was carried
      out using different statistical parameters for the goodness of fit. Both
      chromatographic techniques were considered similarly accurate. The use of
      GC/ISTD, despite showing similar analytical performance to the other
      methodologies, can be considered useful for the harmonization of VFAs analytical
      methodology taking into account the normalization of slope values used for the
      calculation of VFAs concentrations. Acceptance criteria for VFAs performance
      parameters of the multi-laboratory validation study should be established as
      follows: (1) instrument precision (RSDINST<=1.5%); (2) linearity (R(2)>=0.998;
      RSDSENSITIVITY<=4%; REMAX<=8%; REAVER<= 3%); (3) precision (RSD<=1.5%); (4)
      trueness (recovery of 97-103%); (5) LOD (<=3mg/L); and (6) LOQ (10mg/L). 

PMID- 26306913
TI  - Combined Yamamoto approach for simultaneous estimation of adsorption isotherm and
      kinetic parameters in ion-exchange chromatography.
AB  - Application of model-based design is appealing to support the development of
      protein chromatography in the biopharmaceutical industry. However, the required
      efforts for parameter estimation are frequently perceived as time-consuming and
      expensive. In order to speed-up this work, a new parameter estimation approach
      for modelling ion-exchange chromatography in linear conditions was developed. It
      aims at reducing the time and protein demand for the model calibration. The
      method combines the estimation of kinetic and thermodynamic parameters based on
      the simultaneous variation of the gradient slope and the residence time in a set
      of five linear gradient elutions. The parameters are estimated from a Yamamoto
      plot and a gradient-adjusted Van Deemter plot. The combined approach increases
      the information extracted per experiment compared to the individual methods. As a
      proof of concept, the combined approach was successfully applied for a monoclonal
      antibody on a cation-exchanger and for a Fc-fusion protein on an anion-exchange
      resin. The individual parameter estimations for the mAb confirmed that the new
      approach maintained the accuracy of the usual Yamamoto and Van Deemter plots. In
      the second case, offline size-exclusion chromatography was performed in order to
      estimate the thermodynamic parameters of an impurity (high molecular weight
      species) simultaneously with the main product. Finally, the parameters obtained
      from the combined approach were used in a lumped kinetic model to simulate the
      chromatography runs. The simulated chromatograms obtained for a wide range of
      gradient lengths and residence times showed only small deviations compared to the
      experimental data. 

PMID- 26306914
TI  - Development of a mitochondria-based centrifugal ultrafiltration/liquid
      chromatography/mass spectrometry method for screening mitochondria-targeted
      bioactive constituents from complex matrixes: Herbal medicines as a case study.
AB  - Mitochondria are an important intracellular pharmacological target because damage
      to this organelle results in a variety of human disorders and because
      mitochondria are involved in complex processes such as energy generation,
      apoptosis and lipid metabolism. To expedite the search for natural bioactive
      compounds targeting mitochondria, we initially developed an efficient
      mitochondria-based screening method by combining centrifugal ultrafiltration (CU)
      with liquid chromatography/mass spectrometry (LC/MS), which is called screening
      method for mitochondria-targeted bioactive constituents (SM-MBC) and is
      compatible with the search of mitochondria-targeted compounds from complex
      matrixes such as herbal medicines extracts. Functionally active, structurally
      intact and pure mitochondria were obtained from rat myocardium using an optimized
      protocol for mitochondrial isolation comprising organelle release followed by
      differential and Nycodenz density gradient centrifugation. After evaluating the
      reliability of the method using thiabendazole (TZ), rotenone (RN), amiodarone
      (AR) and trimetazidine (TD) as positive controls, this method was successfully
      applied to screen bioactive constituents from extracts of Polygoni Cuspidati
      Rhizoma et Radix (PCRR) and Scutellariae Radix (SR). Nineteen active compounds
      were detected and identified by LC/MS, of which 17 were new mitochondria-targeted
      compounds. The activity of 9 of the 19 hit compounds was confirmed by in vitro
      pharmacological trials. These results demonstrate that SM-MBC can be used for the
      efficient screening of mitochondria-targeted constituents in complex preparations
      used to treat mitochondrial disorders, such as PCRR and SR. The results may be
      meaningful for an in-depth understanding of drug mechanism of action and drug
      discovery from medicinal herbs. 

PMID- 26306915
TI  - Role of mouse Wdr13 in placental growth; a genetic evidence for lifetime body
      weight determination by placenta during development.
AB  - Placental development is essential for implantation and growth of foetus in the
      uterus of eutherian mammals. Numerous growth factors are responsible for
      placental development and cell lineage differentiation. Gene knockout mice have
      shown role of various genes in the placenta. Here using Wdr13 knockout mice, we
      show that this gene is important for proper placental development. Wdr13, a X
      linked gene, expresses in multiple trophoblast cell types of placenta and the
      mutant placenta had reduced size after 17.5 dpc due to reduction of junctional
      zone (JZ) and labyrinth zone (LZ). We observed reduction in levels of
      angiopoietin-2 and cd44 mRNA in Wdr13 mutant placenta as compared to that in the
      wild type. Our findings show that Wdr13 is required for normal placental
      development and cell differentiation. Wdr13 heterozygous female placenta when the
      mutant allele was of maternal origin showed similar defects as those in case of
      Wdr13 null placenta. Using two types of heterozygous females carrying either
      maternally and paternally derived mutant Wdr13 allele we provide genetic evidence
      that development of placenta determines body weight of mice for the entire life. 

PMID- 26306916
TI  - Caspase-7: a critical mediator of optic nerve injury-induced retinal ganglion
      cell death.
AB  - BACKGROUND: Axonal injury of the optic nerve (ON) is involved in various ocular
      diseases, such as glaucoma and traumatic optic neuropathy, which leads to
      apoptotic death of retinal ganglion cells (RGCs) and loss of vision. Caspases
      have been implicated in RGC pathogenesis. However, the role of caspase-7, a
      functionally unique caspase, in ON injury and RGC apoptosis has not been reported
      previously. The purpose of this study is to evaluate the role of caspase-7 in ON
      injury-induced RGC apoptosis. RESULTS: C57BL/6 (wildtype, WT) and caspase-7
      knockout (Casp7(-/-)) mice were used. We show that ON crush activated caspase-7
      and calpain-1, an upstream activator of caspase-7, in mouse RGCs, as well as
      hydrolysis of kinectin and co-chaperone P23, specific substrates of caspase-7. ON
      crush caused a progressive loss of RGCs to 28 days after injury. Knockout of
      caspase-7 partially and significantly protected against the ON injury-induced RGC
      loss; RGC density at 28 days post ON crush in Casp7(-/-) mice was approximately
      twice of that in WT ON injured retinas. Consistent with changes in RGC counts,
      spectral-domain optical coherence tomography analysis revealed that ON crush
      significantly reduced the in vivo thickness of the ganglion cell complex layer
      (including ganglion cell layer, nerve fiber layer, and inner plexiform layer) in
      the retina. The ON crush-induced thinning of retinal layer was significantly
      ameliorated in Casp7(-/-) mice when compared to WT mice. Moreover,
      electroretinography analysis demonstrated a decline in the positive component of
      scotopic threshold response amplitude in ON crushed eyes of the WT mice, whereas
      this RGC functional response was significantly higher in Casp7(-/-) mice at 28
      days post injury. CONCLUSION: Altogether, our findings indicate that caspase-7
      plays a critical role in ON injury-induced RGC death, and inhibition of caspase-7
      activity may be a novel therapeutic strategy for glaucoma and other
      neurodegenerative diseases of the retina.

PMID- 26306918
TI  - RETRACTED ARTICLE: Identification of the Interaction Between the Human Homologue
      of the Arabidopsis COP9 Signalosome Subunit 7a and Olig1.

PMID- 26306917
TI  - Co-administration of ethanol and nicotine: the enduring alterations in the
      rewarding properties of nicotine and glutamate activity within the
      mesocorticolimbic system of female alcohol-preferring (P) rats.
AB  - RATIONALE: The co-abuse of ethanol (EtOH) and nicotine (NIC) increases the
      likelihood that an individual will relapse to drug use while attempting to
      maintain abstinence. There is limited research examining the consequences of long
      term EtOH and NIC co-abuse. OBJECTIVES: The current experiments determined the
      enduring effects of chronic EtOH, NIC, or EtOH + NIC intake on the reinforcing
      properties of NIC and glutamate (GLU) activity within the mesocorticolimbic (MCL)
      system. METHODS: Alcohol-preferring (P) rats self-administered EtOH, Sacc + NIC,
      or EtOH + NIC combined for 10 weeks. The reinforcing properties of 0.1-3.0 MUM
      NIC within the nucleus accumbens shell (AcbSh) were assessed following a 2-3-week
      drug-free period using intracranial self-administration (ICSA) procedures. The
      effects of EtOH, Sacc, Sacc + NIC, or EtOH + NIC intake on extracellular levels
      and clearance of glutamate (GLU) in the medial prefrontal cortex (mPFC) were also
      determined. RESULTS: Binge intake of EtOH (96-100 mg%) and NIC (21-27 mg/mL) were
      attained. All groups of P rats self-infused 3.0 MUM NIC directly into the AcbSh,
      whereas only animals in the EtOH + NIC co-abuse group self-infused the 0.3 and
      1.0 MUM NIC concentrations. Additionally, self-administration of EtOH + NIC, but
      not EtOH, Sacc or Sacc + NIC, resulted in enduring increases in basal
      extracellular GLU levels in the mPFC. CONCLUSIONS: Overall, the co-abuse of EtOH
      + NIC produced enduring neuronal alterations within the MCL which enhanced the
      rewarding properties of NIC in the AcbSh and elevated extracellular GLU levels
      within the mPFC.

PMID- 26306919
TI  - The Noncompetitive AMPAR Antagonist Perampanel Abrogates Brain Endothelial Cell
      Permeability in Response to Ischemia: Involvement of Claudin-5.
AB  - The blood-brain barrier (BBB) is formed by brain endothelial cells, and decreased
      BBB integrity contributes to vasogenic cerebral edema and increased mortality
      after stroke. In the present study, we investigated the protective effect of
      perampanel, an orally active noncompetitive AMPA receptor antagonist, on BBB
      permeability in an in vitro ischemia model in murine brain endothelial cells
      (mBECs). The results showed that perampanel significantly attenuated oxygen
      glucose deprivation (OGD)-induced loss of cell viability, release of lactate
      dehydrogenase, and apoptotic cell death in a dose-dependent manner. Perampanel
      treatment did not alter the expression and surface distribution of various
      glutamate receptors. Furthermore, the results of calcium imaging showed that
      perampanel had no effect on OGD-induced increase in intracellular Ca(2+)
      concentrations. Treatment with perampanel markedly reduced the paracellular
      permeability of mBECs after OGD in different time points, as measured by
      transepithelial electrical resistance assay. In addition, the expression of
      claudin-5 at protein level, but not at mRNA level, was increased by perampanel
      treatment after OGD. Knockdown of claudin-5 partially prevented perampanel
      induced protection in cell viability and BBB integrity in OGD-injured mBECs.
      These data show that the noncompetitive AMPA receptor antagonist perampanel
      affords protection against ischemic stroke through caludin-5 mediated regulation
      of BBB permeability. 

PMID- 26306920
TI  - Is Eotaxin-1 a serum and urinary biomarker for prostate cancer detection and
      recurrence?
AB  - INTRODUCTION AND OBJECTIVES: Eotaxin-1 (CCL11) is a protein expressed in various
      tissues influencing immunoregulatory processes by acting as selective eosinophil
      chemo-attractant. In prostate cancer (PCa), the expression and functional role of
      CCL11 have not been intensively investigated so far. Therefore, the aim of the
      present study was to investigate the diagnostic or prognostic potential of
      Eotaxin-1 in PCa patients. MATERIALS AND METHODS: We analyzed serum from 140
      patients who have undergone prostate biopsy due to elevated prostate-specific
      antigen (PSA) levels as well as serum of 20 individuals with PSA levels < 1ng/ml
      (healthy control group). Moreover, 40 urine samples were analyzed. A custom-made
      Q-Plex array ELISA (Quansys Biosciences) for the detection of Eotaxin-1 was
      performed and Q-View Software used for quantification. In addition, clinical
      courses of patients documented in our Prostate Biobank database were analyzed.
      ROC and survival analyses were used to determine the diagnostic and prognostic
      power of Eotaxin-1 levels. RESULTS: Serum Eotaxin-1 levels were significantly
      decreased in PCa (P = 0.006) as well as in benign prostate hyperplasia (P =
      0.0006) compared to the control group. ROC analysis revealed that Eotaxin-1 is a
      significant marker to distinguish PCa from disease-free prostate. Moreover, we
      found that Eotaxin-1 expression is significantly decreased in Gleason score (GS)
      6 (P = 0.0135) and GS 8 (P = 0.0057) patients compared to samples of healthy men,
      respectively. However, PCa aggressiveness was not predictable by Eotaxin-1
      levels. In line with serum analyses, urine Eotaxin-1 was significantly decreased
      in patients with PCa compared to cancer-free individuals (P = 0.0185) but was not
      different between cancers of different GS. Patients follow-up analyses showed no
      significant correlation between serum Eotaxin-1 levels and time to biochemical
      recurrence. Survival analyses also revealed no significant changes in progression
      free survival among low (<= 112.2 pg/ml) and high (> 112.2 pg/ml) Eotaxin-1 serum
      levels. CONCLUSION: Although this study has not established a prognostic role of
      Eotaxin-1 in PCa patients, this chemokine may serve as a diagnostic marker to
      distinguish between disease-free prostate and cancer.

PMID- 26306922
TI  - Molecular basis of substrate translocation through the outer membrane channel
      OprD of Pseudomonas aeruginosa.
AB  - The objective of this study is to identify the structural features governing the
      transport of molecules through nanometric channel proteins at a molecular level.
      Our focus is to come up with a precise understanding of the structure and
      dynamics of the outer membrane porin OprD of the Gram-negative bacterium
      Pseudomonas aeruginosa by studying the translocation of natural amino acid
      residues/substrates through it. We used in silico electrophysiology and
      metadynamics simulation techniques as they can provide precise information on the
      molecule/channel interactions at the atomic scale that allows testing
      quantitative structure-function relationships. We performed our simulations on
      the whole OprD protein, with all loops modelled and without any constraints to
      keep the channel open. Dynamics of both internal and external loops and the polar
      nature of the eyelet region play important roles in modulating the translocation
      of molecules through OprD by creating two alternative paths for translocation.
      All positive residues take the main path upon binding in the negative pocket just
      above the constriction region. The same factor is unfavourable for negative
      substrates and hence they have a relatively high barrier for translocation.
      Differently, neutral substrates do not show any specificity and they can follow
      the two alternative paths. 

PMID- 26306923
TI  - Treatment of chronic lymphocytic leukemia with monoclonal antibodies, where are
      we heading?
AB  - Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in the western
      world and monoclonal antibodies (mAbs) are important part of CLL treatment. The
      goal of this article was to summarize current literature on the position of mAbs
      in CLL treatment and to mention factors influencing effectiveness of mAbs in CLL.
      Several new mAbs have been developed and investigated in CLL over the past few
      years. Mainly anti-CD20 monoclonal antibodies are still used routinely in CLL
      therapy. Unfortunately, the clinical application of mAbs needs to be further
      improved. Novel combinations and sequences of mAbs with other compounds need to
      be studied in clinical trials in order to increase overall response rate and
      prolong remission duration. Mechanisms of action of mAbs or mechanisms of
      resistance to mAbs have to be also investigated to predict effectiveness of mAb
      in particular patient. 

PMID- 26306921
TI  - Whole Exome Sequencing Reveals Mutations in Known Retinal Disease Genes in 33 out
      of 68 Israeli Families with Inherited Retinopathies.
AB  - Whole exome sequencing (WES) is a powerful technique for identifying sequence
      changes in the human genome. The goal of this study was to delineate the genetic
      defects in patients with inherited retinal diseases (IRDs) using WES. WES was
      performed on 90 patient DNA samples from 68 families and 226 known genes for IRDs
      were analyzed. Sanger sequencing was used to validate potential pathogenic
      variants that were also subjected to segregation analysis in families. Thirty
      three causative mutations (19 novel and 14 known) in 25 genes were identified in
      33 of the 68 families. The vast majority of mutations (30 out of 33) have not
      been reported in the Israeli and the Palestinian populations. Nine out of the 33
      mutations were detected in additional families from the same ethnic population,
      suggesting a founder effect. In two families, identified phenotypes were
      different from the previously reported clinical findings associated with the
      causative gene. This is the largest genetic analysis of IRDs in the Israeli and
      Palestinian populations to date. We also demonstrate that WES is a powerful tool
      for rapid analysis of known disease genes in large patient cohorts. 

PMID- 26306924
TI  - Sensitivity to chromosomal breakage as risk factor in young adults with oral
      squamous cell carcinoma.
AB  - OBJECTIVE: Oral squamous cell carcinoma (OSCC) may develop in young adults. In
      contrast to older patients, the well-known etiological factors, exposure to
      tobacco and alcohol, play a minor role in the carcinogenesis in this patient
      group. It has been suggested that an intrinsic susceptibility to environmental
      genotoxic exposures plays a role in the development of OSCC in these patients.
      The hypothesis was tested whether young OSCC patients have an increased
      sensitivity to induced chromosomal damage. SUBJECTS AND METHODS: Fourteen OSCC
      patients with an average age of 32 years (range 20-42) were selected. Peripheral
      blood lymphocytes and skin fibroblasts of patients and 14 healthy controls were
      subjected to the chromosome breakage test with Mitomycin C. This test is
      routinely used to identify Fanconi anemia patients, who are well-known for their
      inherited high sensitivity to this type of DNA damage, but also for the high risk
      to develop OSCC. Human papilloma virus status of the carcinomas was also
      determined. RESULTS: None of the 14 young patients with OSCC had an increased
      response in the MMC-chromosomal breakage test. All tumors tested negative for
      human papilloma virus. CONCLUSION: No evidence was obtained for the existence of
      a constitutional hypersensitivity to DNA chromosomal damage as a potential risk
      factor for OSCC in young adults.

PMID- 26306925
TI  - Acute effect of fine particulate matter on mortality in three Southeastern states
      from 2007-2011.
AB  - Epidemiologic studies on acute effects of air pollution have generally been
      limited to larger cities, leaving questions about rural populations behind.
      Recently, we had developed a spatiotemporal model to predict daily PM2.5 level at
      a 1 km(2) using satellite aerosol optical depth (AOD) data. Based on the results
      from the model, we applied a case-crossover study to evaluate the acute effect of
      PM2.5 on mortality in North Carolina, South Carolina, and Georgia between 2007
      and 2011. Mortality data were acquired from the Departments of Public Health in
      the States and modeled PM2.5 exposures were assigned to the zip code of residence
      of each decedent. We performed various stratified analyses by age, sex, race,
      education, cause of death, residence, and environmental protection agency (EPA)
      standards. We also compared results of analyses using our modeled PM2.5 levels
      and those imputed daily from the nearest monitoring station. 848,270 non
      accidental death records were analyzed and we found each 10 MUg/m(3) increase in
      PM2.5 (mean lag 0 and lag 1) was associated with a 1.56% (1.19 and 1.94) increase
      in daily deaths. Cardiovascular disease (2.32%, 1.57-3.07) showed the highest
      effect estimate. Blacks (2.19%, 1.43-2.96) and persons with education <= 8 year
      (3.13%, 2.08-4.19) were the most vulnerable populations. The effect of PM2.5 on
      mortality still exists in zip code areas that meet the PM2.5 EPA annual standard
      (2.06%, 1.97-2.15). The effect of PM2.5 below both EPA daily and annual standards
      was 2.08% (95% confidence interval=1.99-2.17). Our results showed more power and
      suggested that the PM2.5 effects on rural populations have been underestimated
      due to selection bias and information bias. We have demonstrated that our AOD
      based exposure models can be successfully applied to epidemiologic studies. This
      will add new study populations in rural areas, and will confer more
      generalizability to conclusions from such studies.

PMID- 26306927
TI  - A voxel-based morphometric magnetic resonance imaging study of the brain detects
      age-related gray matter volume changes in healthy subjects of 21-45 years old.
AB  - Previous and more recent work of analyzing structural changes in the brain
      suggest that certain brain regions such as the frontal lobe are among the brain
      regions profoundly affected by the aging process across males and females. Also,
      a unified model of structural changes in a normally aging brain is still lacking.
      The present study investigated age-related structural brain changes in gray
      matter from young to early middle-age adulthood for males and females. Magnetic
      resonance images of 215 normal and healthy participants between the ages of 21-45
      years were acquired. Changes in gray matter were assessed using voxel-based
      morphometry and gray matter volumetric analysis. The results showed significant
      decrease in gray matter volume between the youngest and oldest groups in the
      following brain regions: frontal, temporal, and parietal lobes. Grey matter loss
      in the frontal lobe was among the most widespread of all brain regions across the
      comparison groups that showed significant age-related changes in grey matter for
      both males and females. This work provides a unique pattern of age-related
      decline of normal and healthy adult males and females that can aid in the future
      development of a unified model of normal brain aging. 

PMID- 26306928
TI  - Vigabatrin-induced MRI changes associated with extrapyramidal symptoms in a child
      with infantile spasms.
AB  - Vigabatrin is an antiepileptic drug used for treatment of infantile spasms. We
      present a female patient with infantile spasms in treatment with vigabatrin who
      developed ataxic movements. MRI demonstrated a symmetrical pattern of thalamic
      and globi pallidi diffusion restriction. While these image features have been
      widely described to be related to the use of vigabatrin, this case highlights the
      development of movement disorders in association with MRI signal changes.
      Awareness of the reversible nature of this condition is reassuring for the
      treating team and avoids unjustified studies. 

PMID- 26306926
TI  - Maternal-infant biomarkers of prenatal exposure to arsenic and manganese.
AB  - Because arsenic (As) and manganese (Mn) are able to pass the placenta, infants
      among exposed populations may be exposed to considerable levels in utero. The
      main objective of this paper is to evaluate infant toenails, hair, and cord blood
      as biomarkers of prenatal exposure to As and Mn and determine the relationship
      between maternal and infant As and Mn concentrations in these biomarkers. Of the
      1196 pregnant women in Bangladesh who were monitored throughout pregnancy until 1
      month post-partum and completed all study visits, we included 711 mother-infant
      pairs who had at least one maternal and one infant biomarker of exposure
      available for analysis. Toenail and hair samples were collected from the women
      during the first trimester and 1 month post-partum and from the infants at the
      age of 1 month. Cord blood was collected at the time of delivery. Maternal
      toenail concentrations were correlated with infant toenail concentrations for As
      and Mn (n=258, r=0.52, 95% CI: 0.43-0.60, P<0.0001 and r=0.39, 95% CI: 0.28-0.49,
      P<0.0001), respectively. Similarly, maternal hair concentrations were correlated
      with infant hair As (n=685, r=0.61, 95% CI: 0.56-0.65, P<0.0001) and infant hair
      Mn (n=686, r=0.21, 95% CI: 0.14-0.28, P<0.0001). Cord blood As was correlated
      with infant toenail and hair As, although cord blood Mn was only correlated with
      infant toenail. Toenails and cord blood appear to be valid biomarkers of maternal
      fetal transfer of As and Mn, whereas hair may not be a suitable biomarker for in
      utero exposure to Mn. 

PMID- 26306929
TI  - Complex aortic arch anomaly: Right aortic arch with aberrant left subclavian
      artery, fenestrated proximal right and duplicated proximal left vertebral
      arteries-CT angiography findings and review of the literature.
AB  - Congenital aortic arch and vertebral artery anomalies are a relatively rare
      finding discovered on imaging either incidentally or for evaluation of entities
      like dysphagia or subclavian steal. Right aortic arch is an uncommon anatomical
      anomaly that occurs in less than 0.1% of the population, and in half of these
      cases the left subclavian artery is also aberrant.(1) Unilateral vertebral artery
      (VA) duplication is rare with an observed prevalence of 0.72% in cadavers.(2)
      Fenestration of the VA is more common than duplication, with a prevalence of
      approximately 0.23%-1.95%.(3,4) We describe the case of a 25-year-old female who
      was found to have a right aortic arch with aberrant left subclavian artery,
      duplicated left vertebral artery and a fenestrated right vertebral artery on CT
      angiography performed for evaluation of dysphagia. This combination of findings
      has not been reported before, to the best of our knowledge. We review the
      embryologic mechanism for the development of the normal aortic arch, right aortic
      arch, vertebral artery duplication and vertebral artery fenestration. The
      incidence of these entities, resultant symptoms and clinical implications are
      also reviewed. The increased associated incidence of aneurysm formation,
      dissection, arteriovenous malformations and thromboembolic events with
      fenestration is also discussed. 

PMID- 26306930
TI  - Reversible restricted-diffusion lesion representing transient intramyelinic
      cytotoxic edema in a patient with traumatic brain injury.
AB  - We report this case to increase the awareness of magnetic resonance imaging (MRI)
      features of reversible white matter abnormalities in diffusion-weighted imaging
      (DWI) and apparent diffusion coefficient (ADC) maps in a patient with traumatic
      brain injury (TBI). An eight-year-old girl, who was hit by a truck, was brought
      to the emergency department by the emergency medical service (EMS). Eleven days
      later, she experienced cognitive impairment requiring MRI evaluation. DWI and ADC
      maps showed restricted diffusion in the white matter of the corpus callosum, peri
      atrial white matter, and in the right centrum semiovale. There were no
      significant hemorrhagic foci in these regions, which showed complete resolution
      on follow up DWI MRI 13 days later. This reported case revealed TBI-related
      transient reversible intramyelinic cytotoxic edema. 

PMID- 26306931
TI  - Glioblastoma complicated by fatal malignant acute ischemic stroke: MRI finding to
      assist in tricky surgical decision.
AB  - BACKGROUND: In most cases, glioblastomas are associated with seizures, headaches,
      neurological deficits, aphasia, or bleeding. But these tumors are rarely
      associated with cerebral infarction and never so deadly. CASE REPORT: A 40-year
      old man presented with sudden morning isolated aphasia. One hour later, he
      developed a motor deficit at right upper member, quickly completed with a total
      right hemiplegia. Imaging studies revealed a left frontotemporal enhancing
      glioblastoma with a perilesional edema which produced an important mass effect on
      the posterior arm of the external capsule, on the primary motor cortex
      posteriorly and the entire sylvian valley anteriorly. Due to major surgical risks
      associated with left middle cerebral artery (MCA) inclusion and large edema, we
      decided to postpone the tumor removal and introduce quickly high concentrations
      of steroids. Twenty-four hours after his admittance, the patient presented a
      sudden impaired consciousness, coma, and a left mydriasis. A brain magnetic
      resonance image (MRI) revealed a left malignant MCA infarction, deadly for the
      patient. CONCLUSION: To our knowledge, glioblastomas complicated by fatal
      ischemic stroke have not been reported. We discuss the pathology of such an event
      and try to figure out if it was predictable based on MRI finding, and inevitable
      with precocious surgery.

PMID- 26306932
TI  - Anterior communicating artery aneurysm: Accuracy of CT angiography in
      determination of inflow dominance.
AB  - BACKGROUND: Preoperative assessment of anterior communicating artery (AcoA)
      aneurysms with cerebral angiography is common, but not without risk. Computed
      tomography angiography (CTA) is a widely available imaging modality that provides
      quick acquisition, low morbidity, and low cost. One disadvantage is that it does
      not provide dynamic information. In this study, the authors sought to determine
      whether CTA alone can reliably predict the inflow dominance to an AcoA aneurysm.
      METHODS: Eighty-three patients with ruptured AcoA aneurysms were reviewed
      retrospectively. Only those patients with both preoperative CTA and cerebral
      angiogram were included, thus excluding six patients. Four independent observers
      reviewed the CTAs and attempted to identify the dominant A1. Additionally, three
      mathematical models were created to identify the dominant A1. These responses
      were compared to cerebral angiograms. RESULTS: Four observers were correct in
      judging the dominant A1 an average of 93% of the time. Seventeen cases were read
      incorrectly by only one of four observers, and three cases were read incorrectly
      by two observers. For cases with incorrect readings, the average percentage
      difference in A1 sizes was 19.6%. For cases read unanimously correct, the average
      percentage difference in A1 sizes was 42.7%. Mathematical model #3 correctly
      evaluated the dominant A1 in 97% of the cases. CONCLUSIONS: This study found CT
      angiograms can be reliable in predicting the inflow dominance to the majority of
      AcoA aneurysms.

PMID- 26306933
TI  - A non-alcoholic Wernicke's encephalopathy case with atypical MRI findings: Clinic
      versus radiology.
AB  - Wernicke's Encephalopathy is an acute neuropsychiatric syndrome that can be seen
      in both alcohol abusers and non-alcoholic population as a result of thiamine
      deficiency. We herein report a non-alcoholic patient with typical clinical
      presentations but atypical MRI findings. Early clinical suspicion of WE is
      especially important in non-alcoholic patients with atypical MRI findings. The
      diagnosis of this group is more difficult to make and the prognosis of the
      syndrome mostly depends on early initiation of thiamine supplementation. 

PMID- 26306934
TI  - The accuracy of clinical symptoms in detecting cauda equina syndrome in patients
      undergoing acute MRI of the spine.
AB  - A large number of patients do not have cauda equina syndrome (CES) on MRI to
      account for their clinical findings; consequently, the majority of urgent scans
      requested are normal. We aimed to determine whether any clinical manifestation of
      CES, as stated in Royal College of Radiology guidelines, could predict the
      presence of established CES on MRI. We also aimed to support a larger study to
      develop a more universal assessment tool for acute lower back pain.A
      retrospective analysis of consecutive patients who warranted urgent MRI was
      conducted. Seventy-nine patients were eligible for study. The Kendall's tau test
      was used for statistical analysis of all data. A p value of less than 0.05 was
      considered to be significant. MRI was performed in 62 patients out of 79.A total
      of 32.9% of patients had scans within 24 hours of admission. Nine of these
      patients were referred to neurosurgery for urgent neurosurgical review. Of these,
      6.3% of patients had an established CES on MRI scan. One patient who had an out
      patient MRI spine (15 days from hospital presentation) was found to have an
      established CES, was urgently referred to spinal surgery and underwent primary
      fenestration excision of the lumbar vertebra. No clinical features that were able
      to predict the presence of an established CES on MRI were elucidated. Findings
      included decreased anal tone 7.6% (p=0.282), faecal incontinence 3.8% (p=0.648),
      urinary retention 7.6% (p=0.510), bladder incontinence 8.9% (p=0.474),
      constipation 2.5% (p=0.011) and saddle anaesthesia 8.9% (p=0.368). Patients who
      had an abnormal MRI spine for back pain prior to this presentation showed a
      correlation with a newly diagnosed CES on MRI (p=0.016) with a correlation
      coefficient of 0.272.

PMID- 26306937
TI  - Mutational mechanisms in MFN2-related neuropathy: compound heterozygosity for
      recessive and semidominant mutations.
AB  - Mitofusin-2 (MFN2) mutations are the most common cause of autosomal dominant
      axonal Charcot-Marie-Tooth disease (CMT, type 2A), sometimes complicated by
      additional features such as optic atrophy (CMT6) and upper motor neuron
      involvement (CMT5). Several pathogenic mutations are reported, mainly acting in a
      dominant fashion, although few sequence variants behaved as recessive or
      semidominant in rare homozygous or compound heterozygous patients. We describe a
      49-year-old woman with CMT5 associated with compound heterozygosity for two MFN2
      variants, one already reported missense mutation (c.748C>T, p.R250W) and a novel
      nonsense sequence change (c.1426C>T, p.R476*). Her mother, carrying the p.R250W
      variant, had very late-onset minimal axonal neuropathy, whilst the father
      harboring the nonsense sequence change had neither clinical nor
      electrophysiological neuropathy. The missense mutation is likely pathogenic
      according to in silico analyses and a previous report, while the nonsense variant
      is predicted to behave as a null allele. The p.R250W variant behaves as
      semidominant by causing only a mild, almost subclinical, neuropathy when
      heterozygous; the nonsense mutation in the father was phenotypically silent,
      suggesting that haploinsufficiency for MFN2 is not disease causative, but was
      deleterious in the daughter who had only one active mutated MFN2 allele. 

PMID- 26306935
TI  - Pharmacologic overview of Withania somnifera, the Indian Ginseng.
AB  - Withania somnifera, also called 'Indian ginseng', is an important medicinal plant
      of the Indian subcontinent. It is widely used, singly or in combination, with
      other herbs against many ailments in Indian Systems of Medicine since time
      immemorial. Withania somnifera contains a spectrum of diverse phytochemicals
      enabling it to have a broad range of biological implications. In preclinical
      studies, it has shown anti-microbial, anti-inflammatory, anti-tumor, anti-stress,
      neuroprotective, cardioprotective, and anti-diabetic properties. Additionally, it
      has demonstrated the ability to reduce reactive oxygen species, modulate
      mitochondrial function, regulate apoptosis, and reduce inflammation and enhance
      endothelial function. In view of these pharmacologic properties, W. somnifera is
      a potential drug candidate to treat various clinical conditions, particularly
      related to the nervous system. In this review, we summarize the pharmacologic
      characteristics and discuss the mechanisms of action and potential therapeutic
      applications of the plant and its active constituents. 

PMID- 26306939
TI  - The clinical importance of accurate measurement of injected doses for
      radionuclide myocardial perfusion imaging.

PMID- 26306938
TI  - Adherence of Tc-99 Sestamibi to Plastic Syringes Could Complicate Efforts in Dose
      Reduction in MPI SPECT.
AB  - BACKGROUND: Multiple disposable syringe designs are available both with and
      without silicone lubricant. Tc99m sestamibi variably adheres to certain syringe
      designs. In practice, this increases pre-injection activity to ensure constant
      acceptable image quality in the setting of high adherence. METHODS: The residual
      activity following 35 Tc99m MDP injections was used as a proxy for the dead-space
      residual activity. This was compared to Tc99m sestamibi injections in the same
      syringe in 107 injections, a syringe without lubricant in 35 injections, and a
      syringe without lubricant or rubber gasket in 16 injections. The syringe with
      lubricated barrel was disassembled and each part separately assayed to see which
      part demonstrated the most adherence. RESULTS: The standard design demonstrated a
      mean adherence of 26% (SD 7.0%). This was significantly more than the 6% (SD
      3.7%) demonstrated with MDP. The two designs without silicone lubricant
      demonstrated mean adherence of 7.2% (SD 2.3%) and 6.4% (SD 2.3%). Disassembly of
      the three part syringe showed the greatest adherence to the rubber gasket.
      CONCLUSIONS: QC procedures determining adherence in the administration syringe
      are warranted for any change in syringe design or manufacturer. If adherence is
      present, conversion to non-lubricated plastic syringes with lower and more
      predictable retention of Tc99m sestamibi enables more precise titration of
      prescribed activities and reduction of overall patient absorbed doses.

PMID- 26306936
TI  - Canonical and noncanonical Wnt signaling in neural stem/progenitor cells.
AB  - The first mammalian Wnt to be discovered, Wnt-1, was found to be essential for
      the development of a large part of the mouse brain over 25 years ago. We have
      since learned that Wnt family secreted glycolipoproteins, of which there are
      nineteen, which activate a diverse network of signals that are particularly
      important during embryonic development and tissue regeneration. Wnt signals in
      the developing and adult brain can drive neural stem cell self-renewal,
      expansion, asymmetric cell division, maturation and differentiation. The
      molecular events taking place after a Wnt binds to its cell-surface receptors are
      complex and, at times, controversial. A deeper understanding of these events is
      anticipated to lead to improvements in the treatment of neurodegenerative
      diseases and stem cell-based replacement therapies. Here, we review the roles
      played by Wnts in neural stem cells in the developing mouse brain, at neurogenic
      sites of the adult mouse and in neural stem cell culture models.

PMID- 26306940
TI  - Use of Enterococcus faecalis and Bacillus atrophaeus as surrogates to establish
      and maintain laboratory proficiency for concentration of water samples using
      ultrafiltration.
AB  - The U.S. Environmental Protection Agency's (EPA) Water Laboratory Alliance (WLA)
      currently uses ultrafiltration (UF) for concentration of biosafety level 3 (BSL
      3) agents from large volumes (up to 100-L) of drinking water prior to analysis.
      Most UF procedures require comprehensive training and practice to achieve and
      maintain proficiency. As a result, there was a critical need to develop quality
      control (QC) criteria. Because select agents are difficult to work with and pose
      a significant safety hazard, QC criteria were developed using surrogates,
      including Enterococcus faecalis and Bacillus atrophaeus. This article presents
      the results from the QC criteria development study and results from a subsequent
      demonstration exercise in which E. faecalis was used to evaluate proficiency
      using UF to concentrate large volume drinking water samples. Based on preliminary
      testing EPA Method 1600 and Standard Methods 9218, for E. faecalis and B.
      atrophaeus respectively, were selected for use during the QC criteria development
      study. The QC criteria established for Method 1600 were used to assess laboratory
      performance during the demonstration exercise. Based on the results of the QC
      criteria study E. faecalis and B. atrophaeus can be used effectively to
      demonstrate and maintain proficiency using ultrafiltration. 

PMID- 26306941
TI  - Role of particle size, shape, and stiffness in design of intravascular drug
      delivery systems: insights from computations, experiments, and nature.
AB  - Packaging of drug molecules within microparticles and nanoparticles has become an
      important strategy in intravascular drug delivery, where the particles are
      designed to protect the drugs from plasma effects, increase drug residence time
      in circulation, and often facilitate drug delivery specifically at disease sites.
      To this end, over the past few decades, interdisciplinary research has focused on
      developing biocompatible materials for particle fabrication, technologies for
      particle manufacture, drug formulation within the particles for efficient
      loading, and controlled release and refinement of particle surface chemistries to
      render selectivity toward disease site for site-selective action. Majority of the
      particle systems developed for such purposes are spherical nano and
      microparticles and they have had low-to-moderate success in clinical translation.
      To refine the design of delivery systems for enhanced performance, in recent
      years, researchers have started focusing on the physicomechanical aspects of
      carrier particles, especially their shape, size, and stiffness, as new design
      parameters. Recent computational modeling studies, as well as, experimental
      studies using microfluidic devices are indicating that these design parameters
      greatly influence the particles' behavior in hemodynamic circulation, as well as
      cell-particle interactions for targeted payload delivery. Certain cellular
      components of circulation are also providing interesting natural cues for
      refining the design of drug carrier systems. Based on such findings, new benefits
      and challenges are being realized for the next generation of drug carriers. The
      current article will provide a comprehensive review of these findings and discuss
      the emerging design paradigm of incorporating physicomechanical components in
      fabrication of particulate drug delivery systems.

PMID- 26306943
TI  - Bibliographic references in PubMed and other search engines: Errare humanum est.

PMID- 26306944
TI  - The relationship between serum and urine NGAL and graft function in pediatric
      renal transplant recipients.

PMID- 26306945
TI  - Role of photopheresis in the treatment of refractory cellular rejection in kidney
      transplantation.

PMID- 26306942
TI  - Virological failure and development of new resistance mutations according to CD4
      count at combination antiretroviral therapy initiation.
AB  - OBJECTIVES: No randomized controlled trials have yet reported an individual
      patient benefit of initiating combination antiretroviral therapy (cART) at CD4
      counts > 350 cells/MUL. It is hypothesized that earlier initiation of cART in
      asymptomatic and otherwise healthy individuals may lead to poorer adherence and
      subsequently higher rates of resistance development. METHODS: In a large cohort
      of HIV-positive individuals, we investigated the emergence of new resistance
      mutations upon virological treatment failure according to the CD4 count at the
      initiation of cART. RESULTS: Of 7918 included individuals, 6514 (82.3%), 996
      (12.6%) and 408 (5.2%) started cART with a CD4 count <= 350, 351-499 and >= 500
      cells/MUL, respectively. Virological rebound occurred while on cART in 488
      (7.5%), 46 (4.6%) and 30 (7.4%) with a baseline CD4 count <= 350, 351-499 and >=
      500 cells/MUL, respectively. Only four (13.0%) individuals with a baseline CD4
      count > 350 cells/MUL in receipt of a resistance test at viral load rebound were
      found to have developed new resistance mutations. This compared to 107 (41.2%) of
      those with virological failure who had initiated cART with a CD4 count < 350
      cells/MUL. CONCLUSIONS: We found no evidence of increased rates of resistance
      development when cART was initiated at CD4 counts above 350 cells/MUL.

PMID- 26306946
TI  - Lupus anticoagulant-hypoprothrombinemia syndrome: A rare association in systemic
      lupus erythematosus.

PMID- 26306947
TI  - Emphysematous pyelonephritis in a renal transplant recipient. A case report.

PMID- 26306948
TI  - Acute renal failure secondary to interstitial acute nephritis and Fanconi
      syndrome for metamizole and gemfibrozil.

PMID- 26306949
TI  - Kidney transplant from a living monozygotic twin donor with no maintenance
      immunosuppression.
AB  - From a theoretical point of view, an alloimmune response can not take place,
      still some type of standard immunosuppression is used in about 60% of patients
      receiving kidney grafts from their monozygotic twins. We aimed at assessing
      clinical response in patients receiving renal grafts from a living monozygotic
      twin donor when no immunosuppressive therapy is used. METHODS: This is a
      retrospective observational study of patients receiving kidney grafts from their
      monozygotic twins from 1969 to 2013. The following data were recorded: age, renal
      graft recipient's primary disease, renal function, renal survival and overall
      survival. Immunosuppressive therapy included a single intraoperative dose of
      methylprednisolone 500 mg and no maintenance immunosuppression. RESULTS: Five
      patients with kidney grafts from their monozygotic twins were dentified in our
      centre. Mean age at transplantation was 33 years (27-39). One-year overall
      survival and graft survival were 100%. Mean creatinine level was 0.96 +/- 0.2 one
      year after transplantation, and 1.2 +/- 0.37 mg/dl at most recent follow-up. Two
      patients died with a functional graft more than 15 years after kidney
      transplantation (causes were melanoma and cardiovascular event respectively).
      Follow-up was lost in a patient one year after transplantation. Two patients are
      alive with a functioning graft at 18 months and 42.5 years after transplantation
      respectively. CONCLUSION: Kidney transplantation from a living monozygotic twin
      is associated to outstanding clinical outcomes. Immunossuppresive therapy to
      suppress alloimmune response in probably unnecessary 11 zygosity has been
      confirmed.

PMID- 26306950
TI  - Role of claudins in renal calcium handling.
AB  - Paracellular channels occurring in tight junctions play a major role in
      transepithelial ionic flows. This pathway includes a high number of proteins,
      such as claudins. Within renal epithelium, claudins result in an ionic
      selectivity in tight junctions. Ascending thick limb of loop of Henle (ATLH) is
      the most important segment for calcium reabsorption in renal tubules. Its cells
      create a water-proof barrier, actively transport sodium and chlorine through a
      transcellular pathway, and provide a paracellular pathway for selective calcium
      reabsorption. Several studies have led to a model of paracellular channel
      consisting of various claudins, particularly claudin-16 and 19. Claudin-16
      mediates cationic paracellular permeability in ATLH, whereas claudin-19 increases
      cationic selectivity of claudin-16 by blocking anionic permeability. Recent
      studies have shown that claudin-14 promoting activity is only located in ATLH.
      When co-expressed with claudin-16, claudin-14 inhibits the permeability of
      claudin-16 and reduces paracellular permeability to calcium. Calcium reabsorption
      process in ATLH is closely regulated by calcium sensor receptor (CaSR), which
      monitors circulating Ca levels and adjusts renal excretion rate accordingly. Two
      microRNA, miR-9 and miR-374, are directly regulated by CaSR. Thus, miR-9 and miR
      374 suppress mRNA translation for claudin-14 and induce claudin-14 decline. 

PMID- 26306951
TI  - Radiofrequency ablation as an alternative therapy for renal neoplasms in graft
      recipients. A preliminary study.

PMID- 26306952
TI  - Repeated serum creatinine measurement in primary care: Not all patients have
      chronic renal failure.
AB  - OBJECTIVE: To assess the prevalence of kidney failure in patients from a primary
      care centre in a basic healthcare district with laboratory availability allowing
      serum creatinine measurements. DESIGN: An observational descriptive cross
      sectional study. DATA SOURCES: A basic healthcare district serving 23,807 people
      aged >= 18 years. RESULTS: Prevalence of kidney failure among 17,240 patients
      having at least one laboratory measurement available was 8.5% (mean age 77.6 +/-
      12.05 years). In 33.2% of such patients an occult kidney failure was found (98.8%
      were women). Prevalence of chronic kidney failure among 10,011 patients having at
      least 2 laboratory measurements available (>= 3 months apart) was 5.5% with mean
      age being 80.1 +/- 10.0 years (most severely affected patients were those aged 75
      to 84); 59.7% were men and 76.3% of cases were in stage 3. An occult kidney
      failure was found in 5.3% of patients with women being 86.2% of them (a
      glomerular filtration rate<60 ml/min was estimated for plasma creatinine levels
      of 0.9 mg/dl or higher). CONCLUSIONS: Comparison of present findings to those
      previously reported demonstrates the need for further studies on the prevalence
      of overall (chronic and acute) kidney failure in Spain in order to estimate the
      real scope of the disease. Primary care physicians play a critical role in
      disease detection, therapy, control and recording (in medical records). MDRD
      equation is useful and practical to estimate glomerular filtration rate.

PMID- 26306953
TI  - Two children with steroid-responsive nephrotic syndrome complicated by cerebral
      venous sinus thrombosis.

PMID- 26306954
TI  - Mesangial nephropathy and anti-synthetase syndrome: An odd association.

PMID- 26306955
TI  - Ceftazidime-avibactam in urinary tract infections due to carbapenemase-producing
      Klebsiella in kidney transplantation.

PMID- 26306956
TI  - Effect of paricalcitol on mineral bone metabolism in kidney transplant recipients
      with secondary hyperparathyroidism.
AB  - INTRODUCTION: Secondary hyperparathyroidism is highly prevalent in kidney
      transplant recipients, and commonly results in hypercalcaemia; an association to
      osteopenia and bone fractures has also been observed. Paricalcitol has proved
      effective to control secondary hyperparathyroidism in chronic kidney disease in
      both dialysed and non-dialysed patients, with a low hypercalcaemia incidence.
      Currently available experience on paricalcitol use in kidney transplant
      recipients is scarce. Our main aim was to show the effect of paricalcitol on
      mineral bone metabolism in kidney transplant recipients with secondary
      hyperparathyroidism. MATERIAL AND METHODS: A retrospective multicentre study in
      kidney transplant recipients aged>18 years with a 12-month or longer post
      transplantation course, stable renal function, having received paricalcitol for
      more than 12 months, with available clinical follow-up for a 24-month period.
      RESULTS: A total of 69 patients with a 120 +/- 92-month post-transplantation
      course were included. Baseline creatinine was 2.2 +/- 0.9 mg/dl y GFR-MDRD was 36
      +/- 20 ml/min/1.73 m(2). Paricalcitol doses were gradually increased during the
      study: baseline 3.8 +/- 1.9 MUg/week, 12 months 5.2 +/- 2.4 MUg/week; 24 months
      6.0 +/- 2.9 MUg/week (P<.001). Serum PTH levels showed a significant fast
      decline: baseline 288 +/- 152 pg/ml; 6 months 226 +/- 184 pg/ml; 12 months 207 +/
      120; 24 months 193 +/- 119 pg/ml (P<.001). Reduction from baseline PTH was >=30%
      in 42.4% of patients at 12 months y in 65.2% of patients at 24 months. Alkaline
      phosphatase showed a significant decrease in first 6 months followed by a
      plateau: baseline 92 +/- 50 IU/l; 6 months 85 +/- 36 IU/l, 12 months 81 +/- 39
      IU/l (P<.001). Overall, no changes were observed in serum calcium and phosphorus,
      and in urine calcium excretion. PTH decline was larger in patients with higher
      baseline levels. Patients with lower baseline calcium levels showed significantly
      increased levels (mean increase was 0.5-0.6 mg/dl) but still within normal range,
      whereas patients with baseline calcium>10mg/dl showed gradually decreasing
      levels. Fifteen (21.7%) patients had received prior calcitriol therapy. When
      shifted to paricalcitol, such patients required paricalcitol doses significantly
      larger than those not having received calcitriol. Paricalcitol was used
      concomitantly to cinacalcet in 11 patients with significant PTH reductions being
      achieved; clinical course was similar to other patients and paricalcitol doses
      were also similar. CONCLUSIONS: Paricalcitol is an effective therapy for
      secondary hyperparathyroidism in kidney transplant recipients. Overall, no
      significant changes were observed in calcium and phosphorus levels or urinary
      excretion. Patients having previously received calcitriol required higher
      paricalcitol doses. When used in patients receiving cinacalcet, paricalcitol
      results in a significant PTH fall, with paricalcitol doses being similar to those
      used in patients not receiving cinacalcet.

PMID- 26306957
TI  - Optimization of dialysate flow in on-line hemodiafiltration.
AB  - INTRODUCTION: Currently, on-line hemodiafiltration (HDF-OL) is the most effective
      technique. Several randomized studies and meta-analyses have shown a reduced
      mortality and a direct association with convective volume has been reported. At
      present, it has not been established if an increased dialysate flow (Qd) results
      in improved results in terms of convective and depurative efficiency. We aim at
      assessing the effects of Qd variations on convective volume and its depurative
      capacity in patients on HDF-OL. MATERIAL AND METHODS: A total of 59 patients (45
      men and 14 women) from a HDF-OL programme in which a monitor 5008 Cordiax with
      self-replacement was used, were enrolled. Patients were assessed in 5 sessions
      with post-dilutional HDF-OL, using helixone-based dialyzers, with only Qd being
      changed (300, 400, 500, 600 and 700ml/min). Serum levels of urea (60Da),
      creatinine (113 Da), beta2-microglobulin (11,800Da), myoglobin (17,200Da) and
      alpha1-microglobulin (33,000Da) were measured at the beginning and at the end of
      each session, in order to estimate the percent reduction of such solutes.
      RESULTS: An increased dialysate volume per session was observed, from 117.9+/-6.4
      L with Qd 300ml/min to 232.4+/-12 L with Qd 700ml/min. No changes were found in
      replacement volume or convective volume. Regarding diffusion, Qd increase was
      associated to a significantly increased dialysis dose, with an increased Kt from
      68+/-6.9 L with Qd 300ml/min to 75.5+/-7.3 L with Qd 700ml/min (p<0,001), and a
      gradually increased percent reduction in urea associated to increased Qd with
      significantly lower levels being found with Qd 300ml/min. No changes were found
      in other measured substances. CONCLUSION: Qd variations in HDF-OL do not change
      convective volume. A higher Qd was associated to a slightly increased urea
      clearance with no change being observed for medium and large molecules. Qd
      optimisation to the minimal level assuring an adequate dialysis dose and allowing
      water and dialysate use to be rationalised should be recommended.

PMID- 26306958
TI  - Overall outcomes in kidney transplant recipients with hepatitis C in a district
      hospital in Camaguey, Cuba.

PMID- 26306959
TI  - Extracapillary glomerulonephritis and leprosy: An uncommon association.

PMID- 26306960
TI  - Iliac artery obliteration as a cause of renovascular hypertension in kidney graft
      recipients: A difficult and uncommon diagnosis.

PMID- 26306961
TI  - Struvite urolithiasis with Corynebacterium urealyticum infection: A case report.

PMID- 26306962
TI  - Gentamicin-based prophylaxis in tunnelled indwelling central venous catheter
      limbs for haemodialysis do not result in bacterial resistances after a 9 year
      follow up period.

PMID- 26306963
TI  - The evolution of occult Hepatitis C Virus after immunosuppression in advanced CKD
      patients.

PMID- 26306964
TI  - Is there any association between overhydration and inflammation in dialysis
      patients?

PMID- 26306965
TI  - Reply to the comment "infection with hepatitis C virus, interferon alpha and
      lupus: an odd association".

PMID- 26306966
TI  - Benefits of a low intensity exercise programme during haemodialysis sessions in
      elderly patients.
AB  - BACKGROUND: Elderly patients on haemodialysis (HD) are a steadily increasing
      group. They show a high complexity, dependency and comorbidity. Multiple benefits
      from exercise in HD patients have been reported; however, they have not been
      specifically evaluated in an elderly population. OBJECTIVE: To assess the effect
      of an adapted low intensity intradialytic exercise programme on muscle strength,
      functional capacity and health-related quality of life in our elderly patients (>
      80 years) on HD. MATERIAL AND METHODS: HD patients were non-randomly assigned to
      an exercise training group (E) or a control group (C) in a 12-week single-centre
      prospective study. E included a combined exercise programme using balls, weights,
      elastic bands and cycle movements in the first 2 hours of HD sessions. C group
      patients received standard HD care. Endpoints were: 1) main biochemical data; 2)
      maximum quadriceps length strength (MQLS) and hand-grip (HG); 3) functional
      capacity tests: "Sit to stand to sit" (STS10) and "six-minutes walking test"
      (6MWT); 4) Beck Depressive Inventory (BDI); and 5) Health-related quality of life
      questionnaire: EuroQol-5D (EQ-5D). RESULTS: A total of 22 patients were included
      (50% men). Mean age was 83.2 years; patients had received HD for 44.1 month.
      Charlson index was 9.5. Main aetiology was diabetes mellitus (36.4%). Eleven
      patients were assigned to E group and 11 to C group. No related adverse effects
      were observed. At the end of the study, E group showed an overall improvement in
      tests (*P<.05): MQLS 10.5 +/- 7.6 vs. 12.9 +/- 10.1 kg, HG* 16.6 +/- 8.7 vs. 18.2
      +/- 8.9 kg, STS10* 29.9 +/- 10.6 vs. 25 +/- 7.87 sec, 6MWT* 14.6%, 234.4 vs.
      274.7 m, BDI* 14.4 +/- 11.5 vs. 11.7 +/- 10.8 and EQ-5D 49 +/- 19.1 vs. 59.5 +/-
      20.3. No similar changes were observed in C group. Significant differences
      between groups were also found for HG, MQLS, STS10, 6MWT, BDI and EQ-5D. No
      significant changes were found in biochemical and anthropometric data,
      antidepressant treatment or suitable dialysis parameters at the end of the study.
      CONCLUSIONS: 1) An adapted low intensity exercise programme improved muscle
      strength, functional capacity and health-related quality of life in our elderly
      patients on HD. 2) Our results highlight the benefits from exercise in HD
      patients even in this elderly population. 3) In elderly patients on HD, it is
      worth considering an adapted low intensity intradialytic exercise programme as a
      part of a comprehensive care.

PMID- 26306967
TI  - Administration of calcimimetics after dialysis: same effectiveness, better
      gastrointestinal tolerability.
AB  - INTRODUCTION: Cinacalcet has proved effective to control secondary
      hyperparathyroidism in patients on haemodialysis (HD). Some studies have reported
      an appropriate secondary hyperparathyroidism control and a better compliance
      after intradialytic use of calcimimetics. OBJECTIVES: To assess the effect of
      post-dialysis calcimimetics use on mineral bone disorders and calcimimetics
      gastrointestinal tolerability in our HD unit. MATERIAL AND METHODS: A 12-week
      single-centre prospective study in HD patients treated with cinacalcet (>2
      months). Two study periods: Usual outpatient use (Stage 1) and use after HD
      session (Stage 2). ENDPOINTS: 1) Biochemical MBD data; 2) Gastrointestinal
      Symptom Rating Scale (GSRS) for gastrointestinal tolerability, and visual
      analogic scale (VAS) for satisfaction; 3) Adherence: Morisky-Green test (MG) and
      final tablet count (TC). RESULTS: Sixty-two HD patients. Fourteen received
      cinacalcet (22.5%). TEN patients were included, mean age was 60.9 years; patients
      had received HD for 80.9 months. Mean Charlson index: 9. Biochemical data: Stage
      1 (initial vs. final): Ca 8.8 +/- 0.5 vs. 9.1 +/- 0.7 mg/dl (p<0.05); P 5.2 +/-
      0.8 vs. 4.5 +/- 1.6 mg/dl, iPTH 360.3 +/- 232.7 vs. 349 +/- 122 pg/ml. MG: 70%.
      Stage 2 (initial vs. final): Ca 9.1 +/- 0.7 vs. 8.8 +/- 0.6 mg/dl; P 4.5 +/- 1.6
      vs. 4.6 +/- 1.3 mg/dl, iPTH 360.3 +/- 232.7 vs. 349 +/- 122 pg/ml. TC: 89%. GSRS
      and VAS were better in Stage 2 (GSRS 7.5 +/- 5.2 vs. 4.3 +/- 1.9; VAS 4.8 +/- 2.3
      vs. 6.9 +/- 2.8). No significant changes were observed in calcimimetic dose (201
      vs. 207 mg/wk), number of phosphate binders (9 vs. 8.2 pts/day), native vitamin D
      (70 vs. 60%), selective vit D receptor activators (30%), or suitable dialysis
      parameters. CONCLUSIONS: Post-dialysis use of calcimimetic was effective in
      secondary hyperparathyroidism control, improved gastrointestinal tolerability and
      ameliorated patients' satisfaction. Based on our findings, post-dialysis use of
      calcimimetics should be considered in selected patients with low therapeutic
      compliance.

PMID- 26306968
TI  - A case report of Gitelman syndrome resulting from two novel mutations in SLC12A3
      gene.
AB  - INTRODUCTION: Hypokalaemia is a common clinical problem. A potential but commonly
      overlooked cause of hypokalaemia is Gitelman syndrome. MATERIAL AND METHODS: A 26
      year-old man was admitted to the hospital due to syncope with general and
      muscular weakness and muscle cramps. The patient's history revealed previous
      recurrent syncope events associated to hypokalaemia with the lowest serum
      potassium value being 2.6mmol/l. At admission, blood pressure was normal and no
      changes were found at physical examination. Laboratory tests showed mild
      hypokalaemia (3.0mmol/l), hypomagnesaemia (1.36mg/dl), hypocalciuria (<
      40mg/24h), and metabolic alkalosis (HCO3(-) 29.7mmol/l, BE 5.3mmol/l). RESULTS:
      Further laboratory tests (FeK, TTKG) confirmed inappropriate kaliuresis. Conn's
      disease was excluded by hormonal and imaging assessments. Genetic testing was
      performed and two novel heterozygous mutations: c.35_36insA and c.1095+5G>A were
      found in transcript NM_000339.2 in SLC12A3 gene. CONCLUSION: The patient was
      diagnosed with Gitelman syndrome and was treated with supplements of potassium
      and magnesium.

PMID- 26306969
TI  - Acute pancreatitis as initial manifestation in an adult patient with focal
      proliferative necrotizing purpura nephritis.

PMID- 26306970
TI  - Haemodialysis session: the perfect storm for vascular calcification.
AB  - INTRODUCTION: Vascular calcification (VC) associated to chronic kidney disease
      (CKD) is a complex phenomenon closely related to mineral bone metabolism
      disorders. Many are the factors implicated, as the drugs used in the treatment of
      CKD. Some in vitro studies suggest that electrolyte and acid-base disorders
      induced by hemodialysis (HD) may play a key role in VC. METHODS: We analyzed
      electrolyte and acid-base disorders that occur during an HD session in 26
      patients randomly assigned to 1,25 mM or 1,5 mM calcium bath. RESULTS: There is a
      calcium load in all the patients, independently of calcium bath concentration or
      basal serum calcium levels. At the end of the session, 100% of the patients
      dialyzed with 1,5 mM calcium bath have calcium serum levels > 1,3 mM. However,
      this only occurs in 15% of the patients dialysed with 1,25 mM calcium bath.
      During this calcium load, phosphorus levels persist uncontrolled. Besides, there
      is a progressive alkalinization in all the patients. In the end of the session
      50% have serum bicarbonate > 30 mM and 23% pH > 7,5. CONCLUSIONS: During HD
      sessions occur electrolyte and acid-base disorders that induce VC: Calcium load
      and alkalization in presence of elevated phosphorus levels. It is necessary to
      perform studies with kinetic models of calcium load and alkalinization different
      from the actual ones.

PMID- 26306971
TI  - A Spanish version for the new ERA-EDTA coding system for primary renal disease.
AB  - BACKGROUND: The European Renal Association and the European Dialysis and
      Transplant Association (ERA-EDTA) have issued an English-language new coding
      system for primary kidney disease (PKD) aimed at solving the problems that were
      identified in the list of "Primary renal diagnoses" that has been in use for over
      40 years. PURPOSE: In the context of Registro Espanol de Enfermos Renales
      (Spanish Registry of Renal Patients, [REER]), the need for a translation and
      adaptation of terms, definitions and notes for the new ERA-EDTA codes was
      perceived in order to help those who have Spanish as their working language when
      using such codes. METHODS: Bilingual nephrologists contributed a professional
      translation and were involved in a terminological adaptation process, which
      included a number of phases to contrast translation outputs. Codes, paragraphs,
      definitions and diagnostic criteria were reviewed and agreements and
      disagreements aroused for each term were labelled. Finally, the version that was
      accepted by a majority of reviewers was agreed. RESULTS: A wide agreement was
      reached in the first review phase, with only 5 points of discrepancy remaining,
      which were agreed on in the final phase. CONCLUSIONS: Translation and adaptation
      into Spanish represent an improvement that will help to introduce and use the new
      coding system for PKD, as it can help reducing the time devoted to coding and
      also the period of adaptation of health workers to the new codes.

PMID- 26306972
TI  - Clinical features, course and prognosis of idiopathic membranous nephropathy
      depending on the presence of antibodies against M-type phospholipase A2 receptor.
AB  - In membranous nephropathy, the presence of antibodies against M-type
      phospholipase A2 receptor is considered highly specific for idiopathic forms.
      However, no specific association to a particular clinical profile has been found
      for such antibodies. OBJECTIVE: To assess potential differences in initial
      clinical profile, course and prognosis of idiopathic membranous nephropathy
      depending on the presence of anti-PLA2R antibodies. METHODS: Eighty-five patients
      with idiopathic membranous nephropathy were included (55 anti-PLA2R-positive and
      30 anti-PLA2R-negative). Clinical, biochemical and pathological variables were
      recorded at the time of diagnosis. Frequency of spontaneous remission, incidence
      of response to first-line therapy, frequency and number of recurrences, survival
      of renal function free from renal replacement therapy, survival of renal function
      free from chronic renal insufficiency and frequency of occurrence of malignant,
      infectious or autoimmune diseases during follow-up were recorded. RESULTS: At the
      time of diagnosis, anti-PLA2R-negative patients were significantly older and had
      a higher frequency of spontaneous remission. No differences were noted in the
      response to first-line treatment, frequency and number of recurrences, survival
      of renal function free from renal replacement therapy, or survival of renal
      function free from chronic renal insufficiency. CONCLUSIONS: Anti-PLA2R-negative
      patients with idiopathic membranous nephropathy were older and experienced
      spontaneous remission more often than anti-PLA2R-positive patients. No
      differences in terms of treatment response, recurrences, and final prognosis were
      observed between both groups of patients.

PMID- 26306973
TI  - Progression of urinary protein excretion after kidney transplantation: A marker
      for poor long-term prognosis.
AB  - INTRODUCTION: Post-transplantation proteinuria is a risk factor for graft
      failure. A progressive decline in renal graft function is a predictor for
      mortality in kidney transplant patients. OBJECTIVES: To assess the development
      and the progression of urinary protein excretion (UPE) in the first year post
      transplant in recipients of kidney transplants and its effect on patient and
      graft outcomes. MATERIALS AND METHODS: We analysed 1815 patients with 24-h UPE
      measurements available at 3 and 12 months post-transplant. Patients were divided
      based on their UPE level: below 300 mg, 300-1000 mg and over 1000 mg (at 3 and 12
      months), and changes over time were analysed. RESULTS: At 3 months, 65.7% had UPE
      below 300 mg/24 h, 29.6% 300-1000 mg/24 h and 4.7% over 1000 mg/24h. At one year,
      71.6% had UPE below 300 mg/24 h, 24.1% 300-1000 mg/24 h and 4.4% over 1000 mg/24
      h. In 208 patients (12%), the UPE progressed, in 1233 (70.5%) it remained stable
      and in 306 (17.5%) an improvement was observed. We found that the level of UPE
      influenced graft survival, particularly if a progression occurred. Recipient's
      age and renal function at one year were found to be predictive factors for
      mortality, while proteinuria and renal function were predictive factors for graft
      survival. CONCLUSIONS: Proteinuria after transplantation, essentially when it
      progresses, is a marker of a poor prognosis and a predictor for graft survival.
      Progression of proteinuria is associated with poorer renal function and lower
      graft survival rates.

PMID- 26306974
TI  - Risk of mortality associated to chronic kidney disease in patients with type 2
      diabetes mellitus: a 13-year follow-up.
AB  - OBJECTIVE: Our aim was to assess the usefulness of glomerular filtration rate
      (GFR) and urinary albumin excretion (UAE) to predict the risk of mortality in
      patients with type 2 diabetes mellitus. MATERIAL AND METHODS: This is a
      prospective cohort study in patients with type 2 diabetes mellitus. Clinical end
      point was mortality rate. GFR was measured in ml/min/1.73 m2 and stratified in 3
      categories (>=60; 45-59; <45); UAE was measured in mg/24hours and was also
      stratified in 3 categories (<30; 30-300; >300). Mortality rates were reported per
      1000 patient-years. Cox regression models were used to predict mortality risk
      associated with combined GFR and UAE. The predictive power was estimated with C
      Harrell statistic. RESULTS: A total of 453 patients (39.3% males), aged 64.9 (SD
      9.3) years were included; mean diabetes duration was 10.4 (SD 7.5) years. Median
      follow-up was 13 years. Total mortality rate was 39.5/1000. The progressive
      increase in mortality in the successive categories of GFR and UAE was
      statistically significant (P<.001). In a multivariable analysis, UAE (HR30
      300=1.02 and HR>300=2.83; X2=11.6; P =.003) and GFR (HR45-59=1.34 and HR<45=1.84;
      X2=6.4; P =.041) were independent predictors for mortality, with no significant
      interaction. Simultaneous inclusion of GFR and UAE improved the predictive power
      of models (C-Harrell 0.741 vs. 0.726; P =.045). CONCLUSIONS: GFR and UAE are
      independent predictors for mortality in type 2 diabetic patients and do not show
      a statistically significant interaction.

PMID- 26306976
TI  - Membranoproliferative glomerulonephritis in a puerperal with Sjogren's syndrome:
      Rare finding or something else?

PMID- 26306975
TI  - Renal transplant patient in emergency department.

PMID- 26306977
TI  - Cloudy peritoneal dialysate effluent due to graft intolerance syndrome.

PMID- 26306978
TI  - Reply to the Letter to the Editor: Is there any association between overhydration
      and inflammation in dialysis patients?

PMID- 26306979
TI  - A Practical and General Base-Catalyzed Carbonylation of Amines for the Synthesis
      of N-Formamides.
AB  - A highly practical and general base-catalyzed carbonylation of amines to the
      corresponding N-formamides has been realized. Cheap inorganic bases, including
      Group IA and IIA metal hydroxides, alkoxides, carbonates, and phosphates, were
      effective catalysts for the transformation. In the presence of 10-40 mol % of KOH
      or K2 CO3 , various amines were converted into the corresponding N-formamides in
      good-to-excellent yields using CO as the formylation reagents.

PMID- 26306980
TI  - Influence of Diurethane Linkers on the Langmuir Layer Behavior of Oligo[(rac
      lactide)-co-glycolide]-based Polyesterurethanes.
AB  - Three oligo[(rac-lactide)-co-glycolide] based polyesterurethanes (OLGA-PUs)
      containing different diurethane linkers are investigated by the Langmuir
      monolayer technique and compared to poly[(rac-lactide)-co-glycolide] (PLGA) to
      elucidate the influence of the diurethane junction units on hydrophilicity and
      packing motifs of these polymers at the air-water interface. The presence of
      diurethane linkers does not manifest itself in the Langmuir layer behavior both
      in compression and expansion experiments when monomolecular films of OLGA-PUs are
      spread on the water surface. However, the linker retard the evolution of
      morphological structures at intermediate compression level under isobaric
      conditions (with a surface pressure greater than 11 mN m-1 ) compared to the
      PLGA, independent on the chemical structure of the diurethane moiety. The layer
      thicknesses of both OLGA-PU and PLGA films decrease in the high compression state
      with decreasing surface pressure, as deduced from ellipsometric data. All films
      must be described with the effective medium approximation as water swollen
      layers.

PMID- 26306981
TI  - Syntheses of new chlorin derivatives containing maleimide functional group and
      their photodynamic activity evaluation.
AB  - Nine new chlorin derivatives containing maleimide functional group and amino acid
      residue with chlorin e6 scaffold (compounds 1-6) or pheophorbide a scaffold
      (compounds 7-9) were synthesised from chlorophyll a. The all nine derivatives
      demonstrated increased photo cytotoxic activity in HepG2 cell (IC50 3.2-20.5 MUM)
      comparing with chlorin e6 and its trimethyl ester. Their photo cytotoxicities
      were approximately dependent on their abilities to produce singlet oxygen ((1)O2)
      in the cells.

PMID- 26306982
TI  - Novel 11beta-HSD1 inhibitors: C-1 versus C-2 substitution and effect of the
      introduction of an oxygen atom in the adamantane scaffold.
AB  - The adamantane scaffold is found in several marketed drugs and in many
      investigational 11beta-HSD1 inhibitors. Interestingly, all the clinically
      approved adamantane derivatives are C-1 substituted. We demonstrate that, in a
      series of paired adamantane isomers, substitution of the adamantane in C-2 is
      preferred over the substitution at C-1 and is necessary for potency at human
      11beta-HSD1. Furthermore, the introduction of an oxygen atom in the hydrocarbon
      scaffold of adamantane is deleterious to 11beta-HSD1 inhibition. Molecular
      modeling studies provide a basis to rationalize these features. 

PMID- 26306983
TI  - Predicting hydration propensities of biologically relevant alpha-ketoamides.
AB  - Quantum chemical calculations coupled to experiments were used to predict
      covalent hydration propensities of biologically relevant alpha-ketoamides.
      Experimentally determined hydration equilibrium constants for related ketones and
      aldehydes were compared to computationally determined values to develop a method
      for predicting hydration equilibrium constants. This method was used on six newly
      synthesized alpha-ketoamides to experimentally verify computational predictions.
      A correlation between calculation and experiment was observed and applied to
      models of several pertinent APIs. Our results indicate that the keto form is
      favored for practically all alpha-ketoamides in biological environs. 

PMID- 26306984
TI  - Risk index for pelvic organ prolapse based on established individual risk
      factors.
AB  - PURPOSE: To identify known risk factors for pelvic organ prolapse (POP) in a
      hospital cohort and to develop a prolapse risk index (PRI). METHODS: Risk factors
      for POP were recorded in women who underwent surgery with symptomatic POP (n =
      500) or non-POP gynaecological conditions (n = 236). Descriptive statistics were
      determined by Chi-squared and Mann-Whitney U tests. Stepwise multivariate
      regression analysis was performed for all patients and subgroups by age (<60 and
      >=60 years). Primary outcome measures were variables with the strongest impact on
      prolapse and PRI development. Secondary: specificity, sensitivity, positive and
      negative predictive values (PPV and NPV, respectively), and Cohen's kappa
      statistic (kappa). RESULTS: Stepwise multivariate regression analysis (n = 736)
      showed difficult obstetric history [odds ratio (OR) 10.04], family history of POP
      (OR 7.28), and >=10 years since menopause (OR 4.53) were independent risk factors
      for prolapse (P < 0.001). When one of the three variables with the strongest
      influence on POP development was present, the PRI for all women showed a PPV of
      82%, NPV of 68%, and kappa of 0.47 for predicting symptomatic POP requiring
      treatment. In women under 60 years (n = 349), logistic regression revealed
      difficult obstetric history (OR 9.108), positive family history (OR 8.016), and
      body mass index (OR 2.274) as independent risk factors. CONCLUSIONS: Eighty-seven
      percent of our patient cohort with symptomatic POP requiring therapy could be
      identified by the PRI, which may be useful for counselling and education.

PMID- 26306985
TI  - Neuroendocrine tumors in the ovary: histogenesis, pathologic differentiation, and
      clinical presentation.
AB  - OBJECTIVE: Primary neuroendocrine tumors in the ovary are rare. These tumors
      arise from the neuroendocrine cell system of ovarian stroma and surface
      epithelium, and may also arise from teratoma. We present four primary ovarian
      neuroendocrine tumors and compare clinicopathologic findings based on tumor
      histogenesis and site of origin. DESIGN: Four primary ovarian neuroendocrine
      tumors were identified from our 10-year departmental archives. H&E slides and
      immunostains were reviewed and the diagnoses were confirmed. Clinical history,
      imaging studies, and follow-up data were obtained from medical records. RESULTS:
      Patients' ages ranged from 26 to 63. All patients presented with abdominal
      discomfort and unilateral or bilateral ovarian masses. MRI and CT scans from
      cases 1 and 2 revealed a solid ovarian mass with no extra-ovarian extension. In
      case 1, the patient also had a cystic mass in the opposite ovary and an elevated
      urine 5-HIAA. Microscopically, case 1 revealed a well-differentiated carcinoid
      tumor with no surface epithelial involvement, and a mature teratoma in the
      contralateral ovary. Case 2 revealed a stromal carcinoid within the ovarian
      parenchyma. Imaging studies from cases 3 and 4 showed large complex masses with
      peritoneal implants and ascites. In both cases 3 and 4, tumor grossly involved
      both ovarian parenchyma and surface epithelium with multiple pelvic implants. In
      addition, liver metastases were present in case 4. Microscopically, these tumors
      were poorly differentiated carcinoma with neuroendocrine differentiation.
      Histologic sections revealed extensive necrosis, and both cases showed positivity
      for neuroendocrine markers. CONCLUSIONS: Primary neuroendocrine tumors in the
      ovary are rare and consist of a group of heterogeneous malignancies that express
      similar immunohistochemical markers. Primary neuroendocrine tumors that are
      limited to the ovarian parenchyma often arise from ovarian stroma and teratoma,
      and are carcinoid tumors with a good prognosis. Neuroendocrine tumors that arise
      from surface epithelium or dedifferentiate from de novo carcinoma often involve
      both ovarian stroma and surface epithelium and clinically present as aggressive
      malignancies with poor prognoses.

PMID- 26306986
TI  - Uterine compression sutures theory.

PMID- 26306987
TI  - Three cornerstones of uterine compression sutures: simplicity, safety and
      efficacy.

PMID- 26306988
TI  - Systems Biology Approaches to a Rational Drug Discovery Paradigm.
AB  - Ligand- and structure-based drug design approaches complement phenotypic and
      target screens, respectively, and are the two major frameworks for guiding early
      stage drug discovery efforts. Since the beginning of this century, the advent of
      the genomic era has presented researchers with a myriad of high throughput
      biological data (parts lists and their interaction networks) to address efficacy
      and toxicity, augmenting the traditional ligand- and structure-based approaches.
      This data rich era has also presented us with challenges related to integrating
      and analyzing these multi-platform and multi-dimensional datasets and translating
      them into viable hypotheses. Hence in the present paper, we review these existing
      approaches to drug discovery research and argue the case for a new systems
      biology based approach. We present the basic principles and the foundational
      arguments/underlying assumptions of the systems biology based approaches to drug
      design. Also discussed are systems biology data types (key entities, their
      attributes and their relationships with each other, and data
      models/representations), software and tools used for both retrospective and
      prospective analysis, and the hypotheses that can be inferred. In addition, we
      summarize some of the existing resources for a systems biology based drug
      discovery paradigm (open TG-GATEs, DrugMatrix, CMap and LINCs) in terms of their
      strengths and limitations. 

PMID- 26306990
TI  - Cognitive emotion regulation enhances aversive prediction error activity while
      reducing emotional responses.
AB  - Cognitive emotion regulation is a powerful way of modulating emotional responses.
      However, despite the vital role of emotions in learning, it is unknown whether
      the effect of cognitive emotion regulation also extends to the modulation of
      learning. Computational models indicate prediction error activity, typically
      observed in the striatum and ventral tegmental area, as a critical neural
      mechanism involved in associative learning. We used model-based fMRI during
      aversive conditioning with and without cognitive emotion regulation to test the
      hypothesis that emotion regulation would affect prediction error-related neural
      activity in the striatum and ventral tegmental area, reflecting an emotion
      regulation-related modulation of learning. Our results show that cognitive
      emotion regulation reduced emotion-related brain activity, but increased
      prediction error-related activity in a network involving ventral tegmental area,
      hippocampus, insula and ventral striatum. While the reduction of response
      activity was related to behavioral measures of emotion regulation success, the
      enhancement of prediction error-related neural activity was related to learning
      performance. Furthermore, functional connectivity between the ventral tegmental
      area and ventrolateral prefrontal cortex, an area involved in regulation, was
      specifically increased during emotion regulation and likewise related to learning
      performance. Our data, therefore, provide first-time evidence that beyond
      reducing emotional responses, cognitive emotion regulation affects learning by
      enhancing prediction error-related activity, potentially via tegmental
      dopaminergic pathways. 

PMID- 26306991
TI  - Auditory midbrain processing is differentially modulated by auditory and visual
      cortices: An auditory fMRI study.
AB  - The cortex contains extensive descending projections, yet the impact of cortical
      input on brainstem processing remains poorly understood. In the central auditory
      system, the auditory cortex contains direct and indirect pathways (via brainstem
      cholinergic cells) to nuclei of the auditory midbrain, called the inferior
      colliculus (IC). While these projections modulate auditory processing throughout
      the IC, single neuron recordings have samples from only a small fraction of cells
      during stimulation of the corticofugal pathway. Furthermore, assessments of
      cortical feedback have not been extended to sensory modalities other than
      audition. To address these issues, we devised blood-oxygen-level-dependent (BOLD)
      functional magnetic resonance imaging (fMRI) paradigms to measure the sound
      evoked responses throughout the rat IC and investigated the effects of bilateral
      ablation of either auditory or visual cortices. Auditory cortex ablation
      increased the gain of IC responses to noise stimuli (primarily in the central
      nucleus of the IC) and decreased response selectivity to forward species-specific
      vocalizations (versus temporally reversed ones, most prominently in the external
      cortex of the IC). In contrast, visual cortex ablation decreased the gain and
      induced a much smaller effect on response selectivity. The results suggest that
      auditory cortical projections normally exert a large-scale and net suppressive
      influence on specific IC subnuclei, while visual cortical projections provide a
      facilitatory influence. Meanwhile, auditory cortical projections enhance the
      midbrain response selectivity to species-specific vocalizations. We also probed
      the role of the indirect cholinergic projections in the auditory system in the
      descending modulation process by pharmacologically blocking muscarinic
      cholinergic receptors. This manipulation did not affect the gain of IC responses
      but significantly reduced the response selectivity to vocalizations. The results
      imply that auditory cortical gain modulation is mediated primarily through direct
      projections and they point to future investigations of the differential roles of
      the direct and indirect projections in corticofugal modulation. In summary, our
      imaging findings demonstrate the large-scale descending influences, from both the
      auditory and visual cortices, on sound processing in different IC subdivisions.
      They can guide future studies on the coordinated activity across multiple regions
      of the auditory network, and its dysfunctions. 

PMID- 26306992
TI  - The microbial community structure of the cotton rat nose.
AB  - The cotton rat nose is commonly used as a model for Staphylococcus aureus
      colonization, as it is both physiologically and anatomically comparable to the
      human nares and can be easily colonized by this organism. However, while the
      colonization of the human anterior nares has been extensively studied, the
      microbial community structure of cotton rat noses has not been reported so far.
      We describe here the microbial community structure of the cotton rat (Sigmodon
      hispidus) nose through next-generation sequencing of 16S rRNA gene amplicons
      covering the V1-V2 region and the analysis of nearly full length 16S rRNA genes
      of the major phylotypes. Roughly half of the microbial community was composed of
      two undescribed species of the genus Campylobacter, with phylotypes belonging to
      the genera Catonella, Acholeplasma, Streptobacillus and Capnocytophaga
      constituting the predominant community members. Thus, the nasal community of the
      cotton rat is uniquely composed of several novel bacterial species and may not
      reflect the complex interactions that occur in human anterior nares. Mammalian
      airway microbiota may, however, be a rich source of hitherto unknown microbes.

PMID- 26306993
TI  - Seed dormancy responses to temperature relate to Nothofagus species distribution
      and determine temporal patterns of germination across altitudes in Patagonia.
AB  - Seeds integrate environmental cues that modulate their dormancy and germination.
      Although many mechanisms have been identified in laboratory experiments, their
      contribution to germination dynamics in existing communities and their
      involvement in defining species habitats remain elusive. By coupling mathematical
      models with ecological data we investigated the contribution of seed temperature
      responses to the dynamics of germination of three Nothofagus species that are
      sharply distributed across different altitudes in the Patagonian Andes. Seed
      responsiveness to temperature of the three Nothofagus species was linked to the
      thermal characteristics of their preferred ecological niche. In their natural
      distribution range, there was overlap in the timing of germination of the
      species, which was restricted to mid-spring. By contrast, outside their species
      distribution range, germination was temporally uncoupled with altitude. This
      phenomenon was described mathematically by the interplay between interspecific
      differences in seed population thermal parameters and the range in soil thermic
      environments across different altitudes. The observed interspecific variations in
      seed responsiveness to temperature and its environmental regulation, constitute a
      major determinant of the dynamics of Nothofagus germination across elevations.
      This phenomenon likely contributes to the maintenance of patterns of species
      abundance across altitude by placing germinated seeds in a favorable environment
      for plant growth. 

PMID- 26306989
TI  - Natural compound-derived epigenetic regulators targeting epigenetic readers,
      writers and erasers.
AB  - Post-translational modifications can affect gene expression in a long-term manner
      without changes in the primary nucleotide sequence of the DNA. These epigenetic
      alterations involve dynamic processes that occur in histones, chromatin
      associated proteins and DNA. In response to environmental stimuli, abnormal
      epigenetic alterations cause disorders in the cell cycle, apoptosis and other
      cellular processes and thus contribute to the incidence of diverse diseases,
      including cancers. In this review, we will summarize recent studies focusing on
      certain epigenetic readers, writers, and erasers associated with cancer
      development and how newly discovered natural compounds and their derivatives
      could interact with these targets. These advances provide insights into
      epigenetic alterations in cancers and the potential utility of these alterations
      as therapeutic targets for the future development of chemopreventive and
      chemotherapeutic drugs. 

PMID- 26306994
TI  - Impact of the dual defence system of Plantago lanceolata (Plantaginaceae) on
      performance, nutrient utilisation and feeding choice behaviour of Amata
      mogadorensis larvae (Lepidoptera, Erebidae).
AB  - Iridoid glycosides are plant defence compounds with potentially detrimental
      effects on non-adapted herbivores. Some plant species possess beta-glucosidases
      that hydrolyse iridoid glycosides and thereby release protein-denaturing
      aglycones. To test the hypothesis that iridoid glycosides and plant beta
      glucosidases form a dual defence system, we used Plantago lanceolata and a
      polyphagous caterpillar species. To analyse the impact of leaf-age dependent
      differences in iridoid glycoside concentrations and beta-glucosidase activities
      on insect performance, old or young leaves were freeze-dried and incorporated
      into artificial diets or were provided freshly to the larvae. We determined
      larval consumption rates and the amounts of assimilated nitrogen. Furthermore, we
      quantified beta-glucosidase activities in artificial diets and fresh leaves and
      the amount of iridoid glycosides that larvae feeding on fresh leaves ingested and
      excreted. Compared to fresh leaves, caterpillars grew faster on artificial diets,
      on which larval weight gain correlated positively to the absorbed amount of
      nitrogen. When feeding fresh young leaves, larvae even lost weight and excreted
      only minute proportions of the ingested iridoid glycosides intact with the
      faeces, indicating that the hydrolysis of these compounds might have interfered
      with nitrogen assimilation and impaired larval growth. To disentangle
      physiological effects from deterrent effects of iridoid glycosides, we performed
      dual choice feeding assays. Young leaves, their methanolic extracts and pure
      catalpol reduced larval feeding in comparison to the respective controls, while
      aucubin had no effect on larval consumption. We conclude that the dual defence
      system of P. lanceolata consisting of iridoid glycosides and beta-glucosidases
      interferes with the nutrient utilisation via the hydrolysis of iridoid glycosides
      and also mediates larval feeding behaviour in a concentration- and substance
      specific manner. 

PMID- 26306995
TI  - A Visualization of the Hamstring Muscle Tendon Complex.

PMID- 26306996
TI  - A Randomized Clinical Trial Comparing Use of Rapid Molecular Testing for
      Staphylococcus aureus for Patients With Cutaneous Abscesses in the Emergency
      Department With Standard of Care.
AB  - OBJECTIVE: To determine whether real-time availability of rapid molecular results
      of Staphylococcus aureus would impact emergency department clinician
      antimicrobial selection for adults with cutaneous abscesses. DESIGN: We performed
      a prospective, randomized controlled trial comparing a rapid molecular test with
      standard of care culture-based testing. Follow-up telephone calls were made at
      between 2 and 7 days, 1 month, and 3 months after discharge. SETTING: Two urban,
      academic emergency departments. PATIENTS: Patients at least 18 years old
      presenting with a chief complaint of abscess, cellulitis, or insect bite and
      receiving incision and drainage were eligible. Seven hundred seventy-eight people
      were assessed for eligibility and 252 met eligibility criteria. METHODS:
      Clinician antibiotic selection and clinical outcomes were evaluated. An ad hoc
      outcome of test performance was performed. RESULTS: We enrolled 252 patients and
      126 were randomized to receive the rapid test. Methicillin-susceptible S. aureus
      positive patients receiving rapid test results were prescribed beta-lactams more
      often than controls (absolute difference, 14.5% [95% CI, 1.1%-30.1%]) whereas
      methicillin-resistant S. aureus-positive patients receiving rapid test results
      were more often prescribed anti-methicillin-resistant S. aureus antibiotics
      (absolute difference, 21.5% [95% CI, 10.1%-33.0%]). There were no significant
      differences between the 2 groups in 1-week or 3-month clinical outcomes.
      CONCLUSION: Availability of rapid molecular test results after incision and
      drainage was associated with more-targeted antibiotic selection. TRIAL
      REGISTRATION clinicaltrials.gov Identifier: NCT01523899.

PMID- 26306997
TI  - Elevated expression of NLRP3 in patients with immune thrombocytopenia.
AB  - Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disease, which is
      characterized by dysregulation of T cell-mediated autoimmunity. NLRP3, a largest
      and mostly well-studied inflammasome, has been shown to be important in the
      regulation of adaptive immune response, especially in T cell response. Given the
      closely association of imbalance of T cell response with ITP, whether NLRP3 is
      involved in the pathogenesis of ITP remains poorly understood. In this study, 69
      active ITP patients, 21 ITP in remission and 24 age- and gender-matched healthy
      controls were included. Peripheral blood mononuclear cells (PBMCs) were isolated
      from ITP and control for isolation of RNA and plasma, which were used to measure
      mRNA level of NLRP3 and adaptor protein ASC by quantitative real-time PCR and IL
      18 plasma level by ELISA. Meanwhile, protein was also extracted from PBMCs for
      Western blot analysis of NLRP3 expression. Our results showed a significantly
      higher expression of NLRP3, ASC and plasma IL-18 level in patients with active
      ITP when compared to control. The expression of NLRP3, ASC and plasma IL-18 level
      was significantly lower in patients in remission than that in active ITP, and no
      difference was observed when compared to control. Furthermore, a significantly
      positive correlation of NLRP3 with ASC was observed in patients with active ITP.
      In conclusion, increased expression of NLRP3 was associated with the pathogenesis
      of ITP and therapeutically targeting it might be a new strategy in the treatment
      of ITP. 

PMID- 26306998
TI  - Does a reduction in alcohol use by Dutch high school students relate to higher
      use of tobacco and cannabis?
AB  - BACKGROUND: Substance use of adolescents was investigated in a region around
      Amsterdam, the Netherlands, in the period 2005-2009. The study was intended to
      find out to what extent behaviour related to different substances are
      interrelated and how trends develop in different subgroups. METHODS: Two cross
      sectional surveys were conducted among Dutch students in the second and fourth
      year of secondary school, aged 13-16 [n = 1,854 in 2005; n = 2,088 in 2009] by
      making use of an online questionnaire including questions about alcohol
      consumption, tobacco use (smoking behaviour) and cannabis use. Two educational
      levels were included. RESULTS: Decreases in alcohol consumption, tobacco and
      cannabis use were found between 2005 and 2009. The strongest decline was seen in
      alcohol consumption. Last month drinking decreased from 61.8% in 2005 to 36.5% in
      2009. Last month binge drinking decreased from 38.7% in 2005 to 24.0% in 2009.
      Reduced alcohol consumption was found among boys and girls, for all ages and in
      both educational levels. Changes were strongest among 13-year-olds. Weekly or
      daily smoking declined between 2005 and 2009 among 13-year-olds, girls and
      students in the lower schooling level. Last month cannabis use decreased among
      girls and students in the higher schooling level. In both 2005 and 2009
      clustering with alcohol consumption was found for the use of other substances.
      CONCLUSIONS: Between 2005 and 2009 alcohol consumption strongly decreased among
      high school students. This may be due to the national prevention campaign which
      in the same period highlighted the importance of not drinking before the age of
      16. The decrease in smoking and cannabis use between 2005 and 2009 may be due to
      clustering with alcohol consumption. A reduction in the use of alcohol in
      adolescence did not lead to replacement by tobacco or cannabis use.

PMID- 26306999
TI  - ZO-1 expression shows prognostic value in chronic B cell leukemia.
AB  - Connexin-mediated gap junctions are vital for tumor cell function. Intracellular
      pathways of connexin signaling use Zonula Occludens protein-1 (ZO-1) as an
      intermediate. This report describes the ZO-1 and connexin 43 (Cx43) expression
      pattern in lymphocytes from chronic B-cell leukemia (B-CLL) patients. The ZO-1
      and Cx43 expression in the B cells of 113 B-CLL patients was identified. Western
      blot and flow cytometry were used to determine protein expression. Results
      indicated that ZO-1 and Cx43 expression was reduced and correlated negatively
      with CD38 and Zap-70 expression. Inhibition of intercellular communication with
      anti-Cx43 antibodies, 1-octanol, or carbenoxolone resulted in induced cell
      apoptosis. These data suggest that ZO-1, along with CD38 and Zap-70, plays a role
      in cell cycle regulation in B-CLL and may be used as a prognostic marker in B-CLL
      monitoring.

PMID- 26307000
TI  - Evaluation of the expression and function of the P2X7 receptor and ART1 in human
      regulatory T-cell subsets.
AB  - Regulatory T cells that express CD39 (CD39+ Treg) exhibit specific
      immunomodulatory properties. Ectonucleotidase CD39 hydrolyses ATP and ADP. ATP is
      a ligand of the P2X7 receptor and induces the shedding of CD62L and apoptosis.
      However, the role of ATP in CD39+ Treg cells has not been defined. Furthermore,
      NAD can activate the P2X7 receptor via ADP-ribosyltransferase (ART) enzymes and
      cause cell depletion in murine models. We evaluated the expression and function
      of P2X7 and ART1 in CD39+ Treg and CD39- Treg cells in the presence or absence of
      ATP and NAD. We isolated peripheral blood mononuclear cells from healthy subjects
      and purified CD4+ T cells, CD4+ CD25+ T cells and CD4+ CD25+ CD39+ T cells. P2X7
      and ART1 expression was assessed by flow cytometry and real-time PCR. Our results
      showed low P2X7 expression on CD39+ Treg cells and higher levels of ART1
      expression in CD4+ CD39+ T cells than the other subtypes studied. Neither
      shedding of CD62L nor cell death of CD39+ Treg or CD39- Treg cells was observed
      by 1mM ATP or 60MUM NAD. In contrast, P2Xs receptor-dependent proliferation with
      300MUM ATP, was inhibited by NAD in the different cell types analysed. The NAD
      proliferation-inhibition was increased with P2Xs and A2a agonist and was reversed
      with P2Xs and A2a antagonist, therefore NAD inhibits P2Xs-dependent proliferation
      and A2a activation. In conclusion, our results suggest that the altered function
      and expression of P2X7 and ART1 in the human CD39+ Treg or CD39- Treg cells could
      participate in the resistance against cell death induced by ATP or NAD.

PMID- 26307001
TI  - Inhibition of the alternative complement pathway by antisense oligonucleotides
      targeting complement factor B improves lupus nephritis in mice.
AB  - Systemic lupus erythematosus is an autoimmune disease that manifests in
      widespread complement activation and deposition of complement fragments in the
      kidney. The complement pathway is believed to play a significant role in the
      pathogenesis and in the development of lupus nephritis. Complement factor B is an
      important activator of the alternative complement pathway and increasing evidence
      supports reducing factor B as a potential novel therapy to lupus nephritis. Here
      we investigated whether pharmacological reduction of factor B expression using
      antisense oligonucleotides could be an effective approach for the treatment of
      lupus nephritis. We identified potent and well tolerated factor B antisense
      oligonucleotides that resulted in significant reductions in hepatic and plasma
      factor B levels when administered to normal mice. To test the effects of factor B
      antisense oligonucleotides on lupus nephritis, we used two different mouse
      models, NZB/W F1 and MRL/lpr mice, that exhibit lupus nephritis like renal
      pathology. Antisense oligonucleotides mediated reductions in circulating factor B
      levels were associated with significant improvements in renal pathology, reduced
      glomerular C3 deposition and proteinuria, and improved survival. These data
      support the strategy of using factor B antisense oligonucleotides for treatment
      of lupus nephritis in humans.

PMID- 26307002
TI  - TIGIT negatively regulates inflammation by altering macrophage phenotype.
AB  - Macrophages function as an essential component of innate immune system,
      contributing to both the initiation and appropriate resolution of inflammation.
      The exposure of macrophages to the microbial products, such as lipopolysaccharide
      (LPS), can strongly shift the balance between tissue homeostasis and inflammation
      in favor of causing systemic damage, in which macrophage M1 polarization play
      important roles. Strategies aiming at restoring the balance of macrophage
      polarization remain to be further explored. Herein, we have demonstrated that
      poliovirus receptor (PVR), the receptor of TIGIT, was dramatically upregulated on
      the surface of mouse peritoneal macrophages when exposed to LPS. TIGIT-Fc fusion
      protein not only inhibited the macrophage activation, but also skewed M1/M2
      balance toward an anti-inflammatory profile, especially enhanced the secretion of
      IL-10. The activation of TIGIT/PVR pathway in macrophages correlated with
      increased nuclear translocation of c-Maf, which promotes IL-10 transcription.
      Treatment with fibroblasts stably secreting TIGIT-Fc fusion protein significantly
      reversed the lethal and sublethal endotoxic shock, which facilitated peritoneal
      macrophages to switch towards anti-inflammatory M2 cytokine profiles. These
      findings highlight a novel role of the TIGIT/PVR pathway in macrophage M2
      polarization and suggest that TIGIT may have the potential to optimize the
      treatment of macrophage-involved inflammatory diseases.

PMID- 26307003
TI  - O-glycosylation effects on family 1 carbohydrate-binding module solution
      structures.
AB  - Family 1 carbohydrate-binding modules (CBMs) are ubiquitous components of
      multimodular fungal enzymes that degrade plant cell wall polysaccharides and bind
      specifically to cellulose. Native glycosylation of family 1 CBMs has been shown
      to substantially impact multiple physical properties, including thermal and
      proteolytic stability and cellulose binding affinity. To gain molecular insights
      into the changes in CBM properties upon glycosylation, solution structures of two
      glycoforms of a Trichoderma reesei family 1 CBM were studied by NMR spectroscopy:
      a glycosylated family 1 CBM with a mannose group attached to both Thr1 and Ser3
      and a second family 1 CBM with single mannose groups attached to Thr1, Ser3 and
      Ser14. The structures clearly reveal that monosaccharides at both Ser3 and Ser14
      on family 1 CBMs present additional cellulose binding platforms, similar to well
      characterized aromatic residues at the binding interface, which align to the
      cellulose surface. These results are in agreement with previous experimental work
      demonstrating that glycans at Ser3 and Ser14 impart significant improvements in
      binding affinity. Additionally, detailed analysis of the NMR structures and
      molecular simulations indicates that the protein backbone of the CBM is not
      significantly altered by attachment of monosaccharides, and that the mannose
      attached to Ser14 may be more flexible than the mannose at Ser3. Overall, the
      present study reveals how family 1 CBM structures are affected by covalent
      attachment of monosaccharides, which are likely important post-translational
      modifications of these common subdomains of fungal plant cell wall degrading
      enzymes. DATABASE: Structural data have been deposited in the RCSB Protein Data
      Bank (PDB codes: 2MWJ and 2MWK) and the BioMagRes Bank (BMRB codes: 25331 and
      25332) for CBM_M2 and CBM_M3, respectively.

PMID- 26307004
TI  - Effects of positive end-expiratory pressure on brain tissue oxygen pressure of
      severe traumatic brain injury patients with acute respiratory distress syndrome:
      A pilot study.
AB  - PURPOSE: To verify whether high positive end-expiratory pressure levels can
      increase brain tissue oxygen pressure, and also their effects on pulse oxygen
      saturation, intracranial pressure, and cerebral perfusion pressure. MATERIAL AND
      METHODS: Twenty traumatic brain injury patients with acute respiratory distress
      syndrome were submitted to positive end-expiratory pressure levels of 5, 10, and
      15 cm H2O progressively. The 3 positive end-expiratory pressure levels were used
      during 20 minutes for each one, whereas brain tissue oxygen pressure, oxygen
      saturation, intracranial pressure, and cerebral perfusion pressure were recorded.
      RESULTS: Brain tissue oxygen pressure and oxygen saturation increased
      significantly with increasing positive end-expiratory pressure from 5 to 10 and
      from 10 to 15 cm H2O (P=.0001 and P=.0001 respectively). Intracranial pressure
      and cerebral perfusion pressure did not differ significantly with increasing
      positive end-expiratory pressure from 5 to 10 and from 10 to 15 cm H2O (P=.16 and
      P=.79 respectively). CONCLUSIONS: High positive end-expiratory pressure levels
      increased brain tissue oxygen pressure and oxygen saturation, without increase in
      intracranial pressure or decrease in cerebral perfusion pressure. High positive
      end-expiratory pressure levels can be used in severe traumatic brain injury
      patients with acute respiratory distress syndrome as a safe alternative to
      improve brain oxygenation.

PMID- 26307005
TI  - Higher-volume hypertonic saline and increased thrombotic risk in pediatric
      traumatic brain injury.
AB  - PURPOSE: Hyperosmolar therapy is a mainstay in the acute medical management of
      traumatic brain injury (TBI). Emerging literature suggests that a hyperosmolar
      state may lead to thrombotic complications. The primary objective of this study
      was to investigate associations between hypertonic saline (HTS) and the outcome
      of deep venous thrombosis (DVT) in pediatric patients with severe TBI. MATERIALS
      AND METHODS: This is a single-center retrospective cohort study of 58 patients
      admitted to the intensive care unit at a Level 1 pediatric trauma center between
      January 2010 and June 2013. Main measurements included volume of HTS
      administration, serum sodium levels, DVT confirmed with ultrasonography, survival
      at 30 days postinjury, and Glasgow Outcome Scale. RESULTS: The cumulative total
      bolus volume of HTS (mL/kg) given to each subject was associated with DVT
      (P=.01). Peak sodium level and 72-hour sustained sodium levels were associated
      with DVT (P=.05). A sustained sodium level of at least 160 mmol/L was associated
      with DVT (P=.02). CONCLUSION: In children with severe TBI, the total bolus volume
      of 3% HTS and sustained sodium levels greater than 160 mmol/L are independently
      associated with DVT.

PMID- 26307006
TI  - Cyanogenetic glycosides and simple glycosides from the linseed meal.
AB  - Three new cyanogenetic triglycosides linustatins A-C (1-3), and two new simple
      glycosides linustatins D and E (4 and 5) were isolated from the 70% ethanol
      extract of flaxseed meal (Linum usitatissimum L.). Their structures were
      elucidated on the basis of spectroscopic analysis and chemical evidence. All of
      the isolates showed moderate activities against aldose reductase and weak
      activities against alpha-glucosidase, DPP-IV, and FBPase at the same
      concentrations as the positive control drugs.

PMID- 26307007
TI  - Feasibility and impact of a computerised clinical decision support system on
      investigation and initial management of new onset chest pain: a mixed methods
      study.
AB  - BACKGROUND: Clinical decision support systems (CDSS) can modify clinician
      behaviour, yet the factors influencing their effect remain poorly understood.
      This study assesses the feasibility and acceptability of a CDSS supporting
      diagnostic and treatment decisions for patients with suspected stable angina.
      METHODS: Intervention The Optimising Management of Angina (OMA) programme
      includes a CDSS guiding investigation and medication decisions for clinicians
      managing patients with new onset stable angina, based on English national
      guidelines, introduced through an educational intervention. Design and
      participants A mixed methods study i. A study of outcomes among patients
      presenting with suspected angina in three chest pain clinics in England before
      and after introduction of the OMA programme. ii. Observations of clinic
      processes, interviews and a focus group with health professionals at two chest
      pain clinics after delivery of the OMA programme. OUTCOMES: Medication and
      cardiovascular imaging investigations undertaken within six months of
      presentation, and concordance of these with the recommendations of the CDSS.
      Thematic analysis of qualitative data to understand how the CDSS was used.
      RESULTS: Data were analysed for 285 patients attending chest pain clinics: 106
      before and 179 after delivery of the OMA programme. 40 consultations were
      observed, 5 clinicians interviewed, and a focus group held after the
      intervention. The proportion of patients appropriate for diagnostic investigation
      who received one was 50 % (95 CI 34-66 %) of those before OMA and 59 % (95 CI 48
      70 %) of those after OMA. Despite high use of the CDSS (84 % of consultations),
      observations and interviews revealed difficulty with data entry into the CDSS,
      and structural and practical barriers to its use. In the majority of cases the
      CDSS was not used to guide real-time decision making, only being consulted after
      the patient had left the room. CONCLUSIONS: The OMA CDSS for the management of
      chest pain is not feasible in its current form. The CDSS was not used to support
      decisions about the care of individual patients. A range of barriers to the use
      of the CDSS were identified, some are easily removed, such as insufficient
      capture of cardiovascular risk, while others are more deeply embedded in current
      practice, such as unavailability of some investigations or no prescribing
      privileges for nurses.

PMID- 26307008
TI  - Visual Snow in Migraine With Aura: Further Characterization by Brain Imaging,
      Electrophysiology, and Treatment--Case Report.
AB  - OBJECTIVE: This study aims to investigate characteristics of visual snow
      accompanied by migraine and special interest on occipital bending,
      electrophysiological properties, and response to treatment. BACKGROUND: Visual
      snow is characterized by continuous dynamically flickering dots in the visual
      field. Most patients also have comorbid migraine. Cortical hyperexcitability is a
      feature of migraine. Recent studies indicate an association between occipital
      bending with psychiatric disorders such as depression. Here, we demonstrate a
      patient with visual snow, migraine with aura, left occipital bending, and
      cortical hyperexcitability. Treatment response to lamotrigine was objectively
      assessed by repetitive pattern reversal visual evoked potentials (rVEP). METHODS:
      A 25-year-old woman with a 10-year history of migraine with aura (2-3
      attacks/week) admitted for 1-year history of visual snow. She reported continuous
      bright and colorful lights, palinopsia, floaters, nyctalopsia, and photopsia.
      Brain magnetic resonance imaging (MRI) was performed. Visual habituation response
      was assessed before and after lamotrigine treatment by rVEP. RESULTS: Brain MRI
      revealed left occipital bending. On rVEP study, there was potentiation response.
      After lamotrigine treatment, the patient had no more complaints of visual snow,
      was able to sleep, and the frequency of migraine decreased to 2 attacks/month.
      Electrophysiologically, the cortical hyperexcitability was improved. CONCLUSIONS:
      The visual snow and loss of habituation ability in migraine associated with
      occipital bending can be improved with lamotrigine treatment. This report may
      provide new insights on "visual snow" pathophysiology in migraine.

PMID- 26307010
TI  - Conformational change results in loss of enzymatic activity of jack bean urease
      on its interaction with silver nanoparticle.
AB  - Urease is an enzyme produced by microbes such as bacteria, yeast and fungi.
      Plants also produce this enzyme. Urease action splits urea into ammonia and
      carbamate. This action is having important implications in agro-chemical,
      medicinal and environment. Therefore there is always a constant search for new
      and novel compounds which could inhibit this enzyme. Here we have studied the
      interaction of jack bean urease (JBU) with silver nanoparticle to analyze the
      influence of the resultant protein corona formation on the catalytic property of
      JBU. Several techniques like UV-Vis, gel shift assay and CD spectroscopy have
      been used to characterize this interaction. Urease activity assay suggests that
      the protein corona formation inhibits the enzymatic action of JBU. The loss of
      enzymatic action could be either due to the nanoparticle blocking the active site
      of JBU or a conformational change in the protein. The CD spectra of JBU-AgNP
      complexes clearly revealed significant changes in the secondary structural
      composition of the JBU and this could be the reason for the loss of enzymatic
      activity of JBU. This study revealed an interesting observation, where the
      interaction of AgNP with JBU resulted destabilization of hexameric nature of JBU
      which is otherwise highly stable. The results of the present study could be
      useful in the development of nanoparticle based material for inhibiting the
      ureolytic activity of ureases in different fields. 

PMID- 26307009
TI  - Distribution of alkaline phosphatase, osteopontin, RANK ligand and
      osteoprotegerin in calcified human carotid atheroma.
AB  - Ectopic vascular calcification is a significant component of atherosclerotic
      disease. Osteopontin (OPN), Osteoprotegerin (OPG), Receptor Activator of NFkappaB
      Ligand (RANKL), and alkaline phosphatase (ALP) are each thought to play central
      roles in the calcification or demineralization of atherosclerotic lesions.
      Abnormalities in the balance of these proteins may lead to perturbations in bone
      remodeling and arterial calcification. The purpose of this study was to measure
      the distribution of these proteins in human carotid lesions and to elucidate
      possible mechanism(s) whereby they control the deposition or depletion of
      arterial calcification. Thirty-three patients who had undergone carotid
      endarterectomy (CEA) within the previous 18 months and 11 control patients were
      enrolled. CEA specimens were analyzed by EBCT for calcification content in terms
      of Agatston (AGAT) and Volume scores. CEA specimens were then cut into 5 mm
      segments which were homogenized and extracted. Extracts were analyzed for tissue
      levels of calcium, phosphorus, ALP, OPN, RANKL, and OPG. Fasting blood samples
      were analyzed for the same components. In CEA tissue segments, the calcification
      levels (CHA AGAT) were inversely associated with the levels of OPG (r = -0.432/
      0.579, p < 0.05) and positively associated with the levels of RANKL (r =
      0.332/0.415, p < 0.05). In turn, the tissue levels of OPG were associated with
      homologous serum levels of OPG (r = 0.820/0.389, p < 0.001), and the tissue
      levels of RANKL were associated with the serum levels of homologous RANKL (r =
      0.739/0.666, p < 0.0001). This study suggests that serum levels of OPG and RANKL
      may be useful biomarkers for estimating the degree of calcification in carotid
      atherosclerotic lesions. 

PMID- 26307011
TI  - The G protein alpha subunit variant XLalphas promotes inositol 1,4,5
      trisphosphate signaling and mediates the renal actions of parathyroid hormone in
      vivo.
AB  - GNAS, which encodes the stimulatory G protein (heterotrimeric guanine nucleotide
      binding protein) alpha subunit (Galphas), also encodes a large variant of Galphas
      termed extra-large alpha subunit (XLalphas), and alterations in XLalphas
      abundance or activity are implicated in various human disorders. Although
      XLalphas, like Galphas, stimulates generation of the second messenger cyclic
      adenosine monophosphate (cAMP), evidence suggests that XLalphas and Galphas have
      opposing effects in vivo. We investigated the role of XLalphas in mediating
      signaling by parathyroid hormone (PTH), which activates a G protein-coupled
      receptor (GPCR) that stimulates both Galphas and Galphaq/11 in renal proximal
      tubules to maintain phosphate and vitamin D homeostasis. At postnatal day 2 (P2),
      XLalphas knockout (XLKO) mice exhibited hyperphosphatemia, hypocalcemia, and
      increased serum concentrations of PTH and 1,25-dihydroxyvitamin D. The ability of
      PTH to reduce serum phosphate concentrations was impaired, and the abundance of
      the sodium phosphate cotransporter Npt2a in renal brush border membranes was
      reduced in XLKO mice, whereas PTH-induced cAMP excretion in the urine was
      modestly increased. Basal and PTH-stimulated production of inositol 1,4,5
      trisphosphate (IP3), which is the second messenger produced by Galphaq/11
      signaling, was repressed in renal proximal tubules from XLKO mice. Crossing of
      XLKO mice with mice overexpressing XLalphas specifically in renal proximal
      tubules rescued the phenotype of the XLKO mice. Overexpression of XLalphas in HEK
      293 cells enhanced IP3 generation in unstimulated cells and in cells stimulated
      with PTH or thrombin, which acts through a Gq/11-coupled receptor. Together, our
      findings suggest that XLalphas enhances Gq/11 signaling to mediate the renal
      actions of PTH during early postnatal development. 

PMID- 26307012
TI  - RelB/p52-mediated NF-kappaB signaling alters histone acetylation to increase the
      abundance of corticotropin-releasing hormone in human placenta.
AB  - Corticotropin-releasing hormone (CRH) produced in the placenta may be part of a
      clock that regulates the length of human gestation. Maternal plasma CRH abundance
      exponentially increases as pregnancy advances. Glucocorticoid stimulates CRH
      expression in full-term human placenta by promoting noncanonical (RelB/p52
      heterodimer-mediated) nuclear factor kappaB (NF-kappaB) pathway activity. Using
      dexamethasone to mimic glucocorticoid exposure, we found that an epigenetic
      switch mediated the glucocorticoid-induced expression of CRH as gestation
      advances. The amount of acetylated histone H3 lysine 9 (H3K9) associated with the
      CRH promoter was greater in cytotrophoblasts from full-term placenta than in
      those from midterm placenta. Knocking down the lysine acetyltransferase CBP
      reduced H3K9 histone acetylation and prevented dexamethasone-induced CRH
      expression. Unexpectedly, knocking down the histone deacetylase HDAC1 or
      pharmacologically inhibiting type I and II HDACs also decreased the expression of
      CRH yet increased the acetylation of H3K9 and other histone regions. Both CBP and
      HDAC1 bound at the CRH promoter in a complex with the RelB/p52 heterodimer in a
      mutually dependent manner; knocking down any one factor in the complex prevented
      binding of the others as well as the dexamethasone-induced CRH expression. Our
      results suggest that glucocorticoids induce a transcription complex consisting of
      RelB/p52, CBP, and HDAC1 that triggers a dynamic acetylation-mediated epigenetic
      change to induce CRH expression in full-term human placenta. 

PMID- 26307014
TI  - Large magnetization and frustration switching of magnetoresistance in the double
      perovskite ferrimagnet Mn2FeReO6.
AB  - Ferrimagnetic A2 BB'O6 double perovskites, such as Sr2 FeMoO6 , are important
      spin-polarized conductors. Introducing transition metals at the A-sites offers
      new possibilities to increase magnetization and tune magnetoresistance. Herein we
      report a ferrimagnetic double perovskite, Mn2 FeReO6 , synthesized at high
      pressure which has a high Curie temperature of 520 K and magnetizations of up to
      5.0 MUB which greatly exceed those for other double perovskite ferrimagnets. A
      novel switching transition is discovered at 75 K where magnetoresistance changes
      from conventional negative tunneling behavior to large positive values, up to 265
      % at 7 T and 20 K. Neutron diffraction shows that the switch is driven by
      magnetic frustration from antiferromagnetic Mn(2+) spin ordering which cants
      Fe(3+) and Re(5+) spins and reduces spin-polarization. Ferrimagnetic double
      perovskites based on A-site Mn(2+) thus offer new opportunities to enhance
      magnetization and control magnetoresistance in spintronic materials. 

PMID- 26307015
TI  - Does Electrification Spur the Fertility Transition? Evidence From Indonesia.
AB  - We analyze various pathways through which access to electricity affects fertility
      in Indonesia, using a district difference-in-difference approach. The
      electrification rate increased by 65 % over the study period, and our results
      suggest that the subsequent effects on fertility account for about 18 % to 24 %
      of the overall decline in fertility. A key channel is increased exposure to
      television. Using in addition several waves of Demographic and Health Surveys, we
      find suggestive evidence that increased exposure to TV affects, in particular,
      fertility preferences and increases the effective use of contraception. Reduced
      child mortality seems to be another important pathway. 

PMID- 26307013
TI  - Extracellular signal-regulated kinase 5 promotes acute cellular and systemic
      inflammation.
AB  - Inflammatory critical illness is a syndrome that is characterized by acute
      inflammation and organ injury, and it is triggered by infections and
      noninfectious tissue injury, both of which activate innate immune receptors and
      pathways. Although reports suggest an anti-inflammatory role for the mitogen
      activated protein kinase (MAPK) extracellular signal-regulated kinase 5 (ERK5),
      we previously found that ERK5 mediates proinflammatory responses in primary human
      cells in response to stimulation of Toll-like receptor 2 (TLR2). We inhibited the
      kinase activities and reduced the abundances of ERK5 and MEK5, a MAPK kinase
      directly upstream of ERK5, in primary human vascular endothelial cells and
      monocytes, and found that ERK5 promoted inflammation induced by a broad range of
      microbial TLR agonists and by the proinflammatory cytokines interleukin-1beta (IL
      1beta) and tumor necrosis factor-alpha (TNF-alpha). Furthermore, we found that
      inhibitors of MEK5 or ERK5 reduced the plasma concentrations of proinflammatory
      cytokines in mice challenged with TLR ligands or heat-killed Staphylococcus
      aureus, as well as in mice that underwent sterile lung ischemia-reperfusion
      injury. Finally, we found that inhibition of ERK5 protected endotoxemic mice from
      death. Together, our studies support a proinflammatory role for ERK5 in primary
      human endothelial cells and monocytes, and suggest that ERK5 is a potential
      therapeutic target in diverse disorders that cause inflammatory critical illness.

PMID- 26307016
TI  - Developmental consequences of behavioral inhibition: a model in rhesus monkeys
      (Macaca mulatta).
AB  - In children, behavioral inhibition is characterized by a disposition to withdraw
      in the presence of strangers and novel situations. Later in life, behavioral
      inhibition can result in an increased risk for anxiety and depression and a
      decrease in social behavior. We selected rhesus monkeys that, during infancy,
      showed evidence of behavioral inhibition in response to separation, and
      contrasted them with non-inhibited peers. To understand the development of
      behavioral inhibition at juvenile age, we collected behavioral data in response
      to relocation; in response to a human intruder challenge; and in naturalistic
      outdoor field corrals. At 4 years of age (young adulthood), we again collected
      behavioral data in the outdoor field corrals to understand the adult social
      consequences of behavioral inhibition. We also included sex, dominance rank, and
      number of available kin in our analyses. Finally, to understand the consistency
      in behavior in behaviorally inhibited animals, we conducted exploratory analyses
      contrasting behaviorally inhibited animals that showed high vs. low durations of
      non-social behaviors as adults. At juvenile age, behaviorally inhibited animals
      continued to show behavioral differences in the novel testing room and during the
      human intruder challenge, generally showing evidence of greater anxiety and
      emotionality compared to non-inhibited controls. In their outdoor corrals,
      behaviorally inhibited juveniles spent more time alone and less time in proximity
      and grooming with mother and other adult females. In young adulthood, we found
      that behavioral inhibition was not related to time spent alone. We did find that
      duration of time alone in adulthood was related to time alone exhibited as
      juveniles; sex, dominance rank, or the number of kin were not influential in
      adult non-social duration, either as main effects or as moderators. Finally,
      exploratory analyses revealed that behaviorally inhibited females that were more
      sociable (less time spent alone) as adults had spent more time grooming as
      juveniles, suggesting that high-quality social interaction at a young age might
      mitigate the social consequences of behavioral inhibition. Overall, we believe
      that the many similarities with the human data that we found suggest that this
      monkey model of naturally occurring behavioral inhibition can be valuable for
      understanding social development.

PMID- 26307017
TI  - Multiple intracardiac masses: myxoma, thrombus or metastasis: a case report.
AB  - INTRODUCTION: The incidence of multiple intracardiac mass is rare. The
      differential diagnosis of intracavitary mass lesions includes benign, malignant
      primary, secondary metastatic cardiac tumors, or thrombus. CASE PRESENTATION: We
      report the case of a 49-year-old Asian woman, who experienced a 2-week history of
      progressive exertional dyspnea, orthopnea, bilateral lower limb edema and
      palpitations. Transthoracic echocardiography showed one fixed round hyperechoic
      mass with central necrosis over the left ventricular apex, one oscillating
      hyperechoic nodule over the anterior mitral annulus and one irregularly
      heterogeneous mass bulging out from the lateral wall of the right atrium. The
      incidence of multiple myxomas is rare. Unfortunately, high tumor marker, serum
      lactic dehydrogenase and serum uric acid levels were also present. We could not
      differentiate between diagnoses of multiple myxomas with thrombi or multiple
      metastatic tumors. CONCLUSIONS: Primary intracardiac tumors are rare.
      Approximately 75% are benign, and approximately 50% are myxomas, which have an
      incidence of 0.0017% in the general population. Multiple intracardiac myxomas
      account for less than 5% of all cases of myxoma. Our case was an atypical picture
      of right atrial (RA) myxoma, as it was located in the RA lateral wall and
      extended to the RA auricle at the junction among the superior and inferior vena
      cava. Two masses in the left ventricle (LV) were thrombi and resolved after
      heparinization. Initially, elevated tumor markers and high serum uric acid and
      high serum lactic dehydrogenase levels were related to necrotic tumor-derived
      tissue, decompensated heart failure with pleural effusion and renal
      insufficiency. We share our experience of multiple intracardiac masses. Whether
      the intracardiac mass is benign or malignant, we recommend surgery due to the
      possibilities of systemic or pulmonary massive embolism, infection, arrhythmia
      and sudden death if the thrombus ruptures or the mass dislodges.

PMID- 26307018
TI  - Nisin Z Production by Lactococcus lactis subsp. cremoris WA2-67 of Aquatic Origin
      as a Defense Mechanism to Protect Rainbow Trout (Oncorhynchus mykiss, Walbaum)
      Against Lactococcus garvieae.
AB  - Probiotics represent an alternative to chemotherapy and vaccination to control
      fish diseases, including lactococcosis caused by Lactococcus garvieae. The aims
      of this study were (i) to determine the in vitro probiotic properties of three
      bacteriocinogenic Lactococcus lactis subsp. cremoris of aquatic origin, (ii) to
      evaluate in vivo the ability of L. cremoris WA2-67 to protect rainbow trout
      (Oncorhynchus mykiss, Walbaum) against infection by L. garvieae, and (iii) to
      demonstrate the role of nisin Z (NisZ) production as an anti-infective mechanism.
      The three L. cremoris strains survived in freshwater at 18  degrees C for 7 days,
      withstood exposure to pH 3.0 and 10 % (v/v) rainbow trout bile, and showed
      different cell surface hydrophobicity (37.93-58.52 %). The wild-type NisZ
      producer L. cremoris WA2-67 and its non-bacteriocinogenic mutant L. cremoris WA2
      67 ?nisZ were administered orally (10(6) CFU/g) to rainbow trout for 21 days and,
      subsequently, fish were challenged with L. garvieae CLG4 by the cohabitation
      method. The fish fed with the bacteriocinogenic strain L. cremoris WA2-67 reduced
      significantly (p < 0.01) the mortality (20 %) compared to the fish treated with
      its non-bacteriocinogenic knockout isogenic mutant (50 %) and the control (72.5
      %). We demonstrated the effectiveness of L. cremoris WA2-67 to protect rainbow
      trout against infection with the invasive pathogen L. garvieae and the relevance
      of NisZ production as an anti-infective mechanism. This is the first report
      demonstrating the effective in vivo role of LAB bacteriocin (NisZ) production as
      a mechanism to protect fish against bacterial infection. Our results suggest that
      the wild-type NisZ-producer strain L. cremoris WA2-67 could be used in fish
      farming to prevent lactococcosis in rainbow trout.

PMID- 26307019
TI  - Next-Generation Transcriptome Profiling of the Salmon Louse Caligus rogercresseyi
      Exposed to Deltamethrin (AlphaMaxTM): Discovery of Relevant Genes and Sex-Related
      Differences.
AB  - Sea lice are one of the main parasites affecting the salmon aquaculture industry,
      causing significant economic losses worldwide. Increased resistance to
      traditional chemical treatments has created the need to find alternative control
      methods. Therefore, the objective of this study was to identify the transcriptome
      response of the salmon louse Caligus rogercresseyi to the delousing drug
      deltamethrin (AlphaMaxTM). Through bioassays with different concentrations of
      deltamethrin, adult salmon lice transcriptomes were sequenced from cDNA libraries
      in the MiSeq Illumina platform. A total of 78 million reads for females and males
      were assembled in 30,212 and 38,536 contigs, respectively. De novo assembly
      yielded 86,878 high-quality contigs and, based on published data, it was possible
      to annotate and identify relevant genes involved in several biological processes.
      RNA-seq analysis in conjunction with heatmap hierarchical clustering evidenced
      that pyrethroids modify the ectoparasitic transcriptome in adults, affecting
      molecular processes associated with the nervous system, cuticle formation,
      oxidative stress, reproduction, and metabolism, among others. Furthermore, sex
      related transcriptome differences were evidenced. Specifically, 534 and 1033
      exclusive transcripts were identified for males and females, respectively, and
      154 were shared between sexes. For males, estradiol 17-beta-dehydrogenase,
      sphingolipid delta4-desaturase DES1, ketosamine-3-kinase, and arylsulfatase A,
      among others, were discovered, while for females, vitellogenin 1, glycoprotein G,
      transaldolase, and nitric oxide synthase were among those identified. The shared
      transcripts included annotations for tropomyosin, gamma-crystallin A, glutamate
      receptor-metabotropic, glutathione S-transferase, and carboxipeptidase B. The
      present study reveals that deltamethrin generates a complex transcriptome
      response in C. rogercresseyi, thus providing valuable genomic information for
      developing new delousing drugs.

PMID- 26307020
TI  - A new appraisal of iodine refractory thyroid cancer.
AB  - Thyroid cancer incidence is increasing all over the world - mostly due to an
      increase in the detection of small tumors that were previously undetected. A
      small percentage of these tumors lose the ability to uptake and/or to respond to
      radioiodine (RAI) therapy, especially in metastatic patients. There are several
      new therapeutic options that have emerged in the last 5 years to treat RAI
      refractory thyroid cancer patients, however, it is very important to properly
      identify RAI refractory patients and to clarify those appropriate for these
      treatments. In this review, we discuss the RAI refractory definitions and the
      criteria that have been suggested based on RAI uptake in the post therapy scan,
      as well as the response after RAI therapy and the possible molecular mechanisms
      involved in this process. We offer a review of the therapeutic options available
      at the moment and the therapeutic considerations based on a patient's
      individualized personal characteristics, primary tumor histology, tumor burden
      and location and velocity of lesion growth. 

PMID- 26307021
TI  - Are we really at the dawn of understanding sporadic pediatric thyroid carcinoma?
AB  - Data from the National Cancer Institute and from the literature have disclosed an
      increasing incidence of thyroid cancer in children, adolescents and adults.
      Although children and adolescents with thyroid cancer tend to present with more
      advanced disease than adults, their overall survival rate is excellent; however,
      there is no clear explanation for the differences observed in the
      clinicopathological outcomes in these age groups. There has been an ongoing
      debate regarding whether the clinicopathological differences may be due to the
      existence of distinct genetic alterations. Efforts have been made to identify
      these acquired genetic abnormalities that will determine the tumor's biological
      behavior and ultimately allow molecular prognostication. However, most of the
      studies have been performed in radiation-exposed pediatric thyroid carcinoma.
      Therefore, our understanding of the role of these driver mutations in sporadic
      pediatric differentiated thyroid cancer development is far from complete, and
      additionally, there is a strong need for studies in both children and
      adolescents. The aim of this review is to present an extensive literature review
      with emphasis on the molecular differences between pediatric sporadic and
      radiation-exposed differentiated thyroid carcinomas and adult population. 

PMID- 26307023
TI  - Thyroid hormones and tetrac: new regulators of tumour stroma formation via
      integrin alphavbeta3.
AB  - To improve our understanding of non-genomic, integrin alphavbeta3-mediated
      thyroid hormone action in tumour stroma formation, we examined the effects of
      triiodo-l-thyronine (T3), l-thyroxine (T4) and integrin-specific inhibitor tetrac
      on differentiation, migration and invasion of mesenchymal stem cells (MSCs) that
      are an integral part of the tumour's fibrovascular network. Primary human bone
      marrow-derived MSCs were treated with T3 or T4 in the presence of hepatocellular
      carcinoma (HCC) cell-conditioned medium (CM), which resulted in stimulation of
      the expression of genes associated with cancer-associated fibroblast-like
      differentiation as determined by qPCR and ELISA. In addition, T3 and T4 increased
      migration of MSCs towards HCC cell-CM and invasion into the centre of three
      dimensional HCC cell spheroids. All these effects were tetrac-dependent and
      therefore integrin alphavbeta3-mediated. In a subcutaneous HCC xenograft model,
      MSCs showed significantly increased recruitment and invasion into tumours of
      hyperthyroid mice compared to euthyroid and, in particular, hypothyroid mice,
      while treatment with tetrac almost completely eliminated MSC recruitment. These
      studies significantly improve our understanding of the anti-tumour activity of
      tetrac, as well as the mechanisms that regulate MSC differentiation and
      recruitment in the context of tumour stroma formation, as an important
      prerequisite for the utilisation of MSCs as gene delivery vehicles. 

PMID- 26307024
TI  - The Palpable Scaphoid Surface Area in Various Wrist Positions.
AB  - PURPOSE: To determine the theoretical amount of surface area available for
      palpation of the scaphoid in various wrist positions and to provide a guide
      depicting which wrist position will expose proximal pole, waist, and distal pole
      fractures. METHODS: Using 3 fresh-frozen male cadaver wrists, we digitized
      palpable surface areas (dorsal, volar, and snuffbox) of the scaphoid in several
      wrist positions. The entire scaphoid was then excised and a digitized 3
      dimensional reconstruction of the entire scaphoid was obtained. The 2 images were
      superimposed and the surface area was calculated RESULTS: The maximum palpable
      area of the scaphoid was achieved with the wrist in neutral extension and maximum
      ulnar deviation and the wrist in maximum flexion and neutral deviation. Neutral
      wrist extension and ulnar deviation exposed all but the most proximal portion of
      the proximal pole and the distal pole, which made this the ideal position to
      detect tenderness from a scaphoid waist fracture and larger proximal pole
      fractures. Maximum wrist flexion with neutral wrist deviation exposed the entire
      proximal pole, which made this the ideal position to detect tenderness from a
      proximal pole scaphoid fracture. CONCLUSIONS: Wrist position influences the
      amount of scaphoid surface area available for palpation and should be considered
      when examining a patient with a suspected scaphoid fracture. CLINICAL RELEVANCE:
      The scaphoid should be palpated in 3 anatomic regions with the wrist placed in
      different positions to maximally expose the anatomical region being palpated.

PMID- 26307022
TI  - The many ways to make a luminal cell and a prostate cancer cell.
AB  - Research in the area of stem/progenitor cells has led to the identification of
      multiple stem-like cell populations implicated in prostate homeostasis and cancer
      initiation. Given that there are multiple cells that can regenerate prostatic
      tissue and give rise to prostate cancer, our focus should shift to defining the
      signaling mechanisms that drive differentiation and progenitor self-renewal. In
      this article, we will review the literature, present the evidence and raise
      important unanswered questions that will help guide the field forward in
      dissecting critical mechanisms regulating stem-cell differentiation and tumor
      initiation. 

PMID- 26307025
TI  - Systemic review: the pathogenesis and pharmacological treatment of hiccups.
AB  - BACKGROUND: Hiccups are familiar to everyone, but remain poorly understood. Acute
      hiccups can often be terminated by physical manoeuvres. In contrast, persistent
      and intractable hiccups that continue for days or months are rare, but can be
      distressing and difficult to treat. AIM: To review the management of hiccups,
      including a systematic review of reported efficacy and safety of pharmacological
      treatments. METHODS: Available articles were identified using three electronic
      databases in addition to hand searching of published articles. Inclusion criteria
      were any reports of pharmaceutical therapy of 'hiccup(s)', 'hiccough(s)' or
      'singultus' in English or German. RESULTS: Treatment of 341 patients with
      persistent or intractable hiccups was reported in 15 published studies.
      Management was most effective when directed at the underlying condition. An
      empirical trial of anti-reflux therapy may be appropriate. If the underlying
      cause is not known or not treatable, then a range of pharmacological agents may
      provide benefit; however, systematic review revealed no adequately powered, well
      designed trials of treatment. The use of baclofen and metoclopramide are
      supported by small randomised, placebo-controlled trials. Observational data
      suggest that gabapentin and chlorpromazine are also effective. Baclofen and
      gabapentin are less likely than standard neuroleptic agents to cause side effects
      during long-term therapy. CONCLUSIONS: This systematic review revealed no high
      quality data on which to base treatment recommendations. Based on limited
      efficacy and safety data, baclofen and gabapentin may be considered as first line
      therapy for persistent and intractable hiccups, with metoclopramide and
      chlorpromazine in reserve.

PMID- 26307026
TI  - Reducing Risk for Substance Use by Economically Disadvantaged Young Men: Positive
      Family Environments and Pathways to Educational Attainment.
AB  - Using prospective, longitudinal data spanning 10 years (age = 10-20) from a study
      of 295 economically disadvantaged males, the current investigation evaluated a
      developmental model that links early family environment and later educational
      aspirations, extracurricular activities, and educational attainment to substance
      use in early adulthood. The results indicate that a positive family environment
      during adolescence (low family conflict, high family warmth, and effective child
      management) predicted educational involvements during adolescence that promoted
      educational attainment during early adulthood. Finally, higher levels of
      educational attainment were associated with less substance use in early
      adulthood, even after controlling for adolescent substance use. These findings
      suggest that positive parenting promotes educational achievements that increase
      resilience to substance use for economically disadvantaged males.

PMID- 26307027
TI  - Unactivated C(sp(3))-H hydroxylation through palladium catalysis with H2O as the
      oxygen source.
AB  - A novel palladium catalyzed hydroxylation of unactivated aliphatic C(sp(3))-H
      bonds was successfully developed. Different from conventional methods, water
      serves as the hydroxyl group source in the reaction. This new reaction
      demonstrates good reactivity and broad functional group tolerance. The C-H
      hydroxylated products can be readily transformed into various highly valuable
      chemicals via known transformations. Based on experimental and theoretical
      studies, a mechanism involving the Pd(II)/(IV) pathway is proposed for this
      hydroxylation reaction.

PMID- 26307028
TI  - Noncontrast-Enhanced Magnetic Resonance Versus Computed Tomography Angiography in
      Preoperative Evaluation of Potential Living Renal Donors.
AB  - RATIONALE AND OBJECTIVES: Living renal donors undergo an extensive examination
      program. These examinations should be as safe, gentle, and patient friendly as
      possible. To compare computed tomography angiography (CTA) and an extensive
      magnetic resonance imaging (MRI) protocol without contrast agents to observations
      from nephrectomy in living renal donors and to evaluate whether noncontrast
      enhanced MRI can replace CTA for vessel assessment in living renal donors.
      MATERIAL AND METHODS: CTA and MRI results were compared to observations from
      nephrectomy, which served as the reference standard. Fifty-one potential kidney
      donors underwent imaging, and 31 donated a kidney. Comparisons in sensitivity,
      specificity, and accuracy were made with respect to the number of arteries, early
      branching, and the number of veins. Agreement was assessed using Cohen's kappa.
      The exact McNemar's test was used to test for statistically significant
      differences. RESULTS: In the assessment of more than one renal artery, the
      sensitivity and specificity of MRI and CTA were high and in perfect agreement
      compared to observations from surgery. The results for both MRI and CTA were as
      follows: (sensitivity 100%/specificity100%/accuracy 100%/Kappa = 1/P = 1). When
      comparing the ability to test for early branching we found, MRI: (sensitivity
      33%/specificity 100%/accuracy 87%/Kappa = 0.45/P = 1) and CTA: (sensitivity
      50%/specificity 100%/accuracy 90%/Kappa = 0.62/P = 1). When used to depict
      supernumerary veins, we found MRI: (sensitivity60%/specifivity100%/accuracy
      93%/Kappa = 0.72/P = 1), whereas CTA showed: (sensitivity 40%/specificity
      96%/accuracy 87% Kappa = 0.43/P = 1). CONCLUSIONS: In conclusion, an optimized
      MRI protocol that includes noncontrast-enhanced magnetic resonance angiography
      can be substituted for CTA for preoperative assessment of the renal vessels
      before living donor nephrectomy.

PMID- 26307029
TI  - Streptomyces kanasensis sp. nov., an Antiviral Glycoprotein Producing
      Actinomycete Isolated from Forest Soil Around Kanas Lake of China.
AB  - A filamentous actinomycete, designated strain ZX01(T), was isolated from forest
      soil around Kanas Lake of China. A polyphasic taxonomic study was carried out to
      establish the status of strain ZX01(T). Chemical and morphological properties of
      the isolate were similar to those of species of the genus Streptomyces. Analysis
      of the almost complete 16S rRNA gene sequence placed strain ZX01(T) in the genus
      Streptomyces where it formed a distinct phyletic line with recognized species of
      this genus. The strain exhibited the highest sequence similarities to
      Streptomyces lavendofoliae NBRC 12882(T) (99.1%), S. luridus NBRC 12793(T)
      (99.0%), S. lavendulocolor NBRC 12881(T) (99.0%), S. gobitricini NBRC 15419(T)
      (99.0%), and S. roseolilacinus NBRC 12815(T) (98.9%). Low DNA-DNA relatedness
      values of 54.0, 50.0, 60.0, 66.7, and 50.4%, respectively, were found between
      strain ZX01(T) and corresponding strains above. A number of phenotypic properties
      also enabled the isolate to be differentiated from related species of the genus
      Streptomyces. Therefore, it is proposed that strain ZX01(T) should be classified
      as the type strain of a novel species in the genus Streptomyces, Streptomyces
      kanasensis sp. nov. The type strain is ZX01(T) (= CGMCC 4893(T) =JCM 30232(T)).

PMID- 26307030
TI  - DNA Methylation of the Aryl Hydrocarbon Receptor Repressor Associations With
      Cigarette Smoking and Subclinical Atherosclerosis.
AB  - BACKGROUND: Tobacco smoke contains numerous agonists of the aryl hydrocarbon
      receptor (AhR) pathway, and activation of the AhR pathway was shown to promote
      atherosclerosis in mice. Intriguingly, cigarette smoking is most strongly and
      robustly associated with DNA modifications to an AhR pathway gene, the AhR
      repressor (AHRR). We hypothesized that altered AHRR methylation in monocytes, a
      cell type sensitive to cigarette smoking and involved in atherogenesis, may be a
      part of the biological link between cigarette smoking and atherosclerosis.
      METHODS AND RESULTS: DNA methylation profiles of AHRR in monocytes (542 CpG sites
      +/- 150 kb of AHRR, using Illumina 450K array) were integrated with smoking
      habits and ultrasound-measured carotid plaque scores from 1256 participants of
      the Multi-Ethnic Study of Atherosclerosis (MESA). Methylation of cg05575921
      significantly associated (P=6.1 * 10(-134)) with smoking status (current versus
      never). Novel associations between cg05575921 methylation and carotid plaque
      scores (P=3.1 * 10(-10)) were identified, which remained significant in current
      and former smokers even after adjusting for self-reported smoking habits, urinary
      cotinine, and well-known cardiovascular disease risk factors. This association
      replicated in an independent cohort using hepatic DNA (n=141). Functionally,
      cg05575921 was located in a predicted gene expression regulatory element
      (enhancer) and had methylation correlated with AHRR mRNA profiles (P=1.4 * 10(
      17)) obtained from RNA sequencing conducted on a subset (n=373) of the samples.
      CONCLUSIONS: These findings suggest that AHRR methylation may be functionally
      related to AHRR expression in monocytes and represents a potential biomarker of
      subclinical atherosclerosis in smokers.

PMID- 26307031
TI  - Pharmacological inhibition of DNA-PK stimulates Cas9-mediated genome editing.
AB  - BACKGROUND: The ability to modify the genome of any cell at a precise location
      has drastically improved with the recent discovery and implementation of
      CRISPR/Cas9 editing technology. However, the capacity to introduce specific
      directed changes at given loci is hampered by the fact that the major cellular
      repair pathway that occurs following Cas9-mediated DNA cleavage is the erroneous
      non-homologous end joining (NHEJ) pathway. Homology-directed recombination (HDR)
      is far less efficient than NHEJ and makes screening of clones containing directed
      changes time-consuming and labor-intensive. METHODS: We investigated the
      possibility of pharmacologically inhibiting DNA-PKcs, a key player in NHEJ, using
      small molecule inhibitors (NU7441 and KU-0060648), to ameliorate the rates of HDR
      repair events. These compounds were tested in a sensitive reporter assay capable
      of simultaneously informing on NHEJ and HDR, as well as on an endogenous gene
      targeted by Cas9. RESULTS: We find that NU7441 and KU-0060648 reduce the
      frequency of NHEJ while increasing the rate of HDR following Cas9-mediated DNA
      cleavage. CONCLUSIONS: Our results identify two small molecules compatible for
      use with Cas9-editing technology to improve the frequency of HDR.

PMID- 26307033
TI  - Psychopharmacological Agents and Suicide Risk Reduction: Ketamine and Other
      Approaches.
AB  - Suicide is a major global public health problem and the leading cause of injury
      mortality in the USA. Suicide is a complex phenomenon involving several systems
      and neurobiological pathways, with interacting genetic and environmental
      mechanisms. The literature on the neurobiology and pharmacotherapy of suicide has
      been limited. To date, no medications have proven efficacious for treating acute
      suicidal crises. There is an emerging literature supporting a rapid anti-suicidal
      effect of ketamine, a non-competitive N-methyl-D-aspartate (NMDA) glutamate
      receptor antagonist, among depressed patients with suicidal ideation. Potential
      ketamine's anti-suicidal effect mechanisms are linked to interruption of the
      kynurenine pathway and modulating pro-inflammatory cytokines exacerbation.
      However, available data are not sufficient for its routine integration in
      clinical practice, and larger and replicated randomized control studies are
      needed. 

PMID- 26307032
TI  - Aberrant expression of Notch1/numb/snail signaling, an epithelial mesenchymal
      transition related pathway, in adenomyosis.
AB  - BACKGROUND: Epithelial mesenchymal transition (EMT) is involved in the
      pathogenesis of adenomyosis, and Notch signaling is crucial to EMT. The objective
      of this study was to explore Notch1/Numb/Snail signaling in adenomyosis. METHODS:
      The expression levels of the members of the Notch1/Numb/Snail signaling cascade
      in normal endometria (proliferative phase: n = 15; secretory phase: n = 15;
      postmenopausal phase: n = 15) and adenomyotic endometria (proliferative phase: n
      = 15; secretory phase: n = 15) were determined by immunohistochemistry analysis.
      RESULTS: We found that the expressions of Notch1 and the EMT-related proteins N
      cadherin, Snail and Slug were upregulated in the ectopic endometrium of
      adenomyosis compared with normal endometrium. Numb, a negative regulator of Notch
      signaling, was significantly decreased in adenomyosis. In addition, reduced
      immunoexpression of E-cadherin was observed in adenomyosis. CONCLUSIONS: We
      conclude that Notch1/Numb/Snail signaling plays an important role in the
      pathogenesis and development of adenomyosis.

PMID- 26307034
TI  - A Case Study of the Perversion Files: An Application of Lanning and Dietz
      "Commonly Misunderstood Phenomena".
AB  - The fight against child sexual abuse has been hindered by the refusal of many
      public organizations to release information or to report allegations of
      misconduct. Brought to the public's attention only when the accused is a well
      known person, organizations designed to support children in many aspects of their
      lives have allowed for decades of abuse to go unchecked. In October of 2012, the
      Oregon Supreme court ordered the Boy Scouts of American (BSA) to release 14,500
      pages of confidential files detailing sexual abuse allegations from 1959 to 1985.
      The so-called "perversion files" are the single largest collection of information
      on alleged perpetrators of sexual molestation against youth. The BSA data
      represented a unique opportunity to examine demographic information from a large
      sample of purported sexual offenders from across the country over a vast period
      of time. Additionally, the sexual offenders were not exclusively located in the
      criminal justice system since BSA officials referred only a small percentage of
      offenders to law enforcement. The study analyzed a random sample to ascertain
      description of the actions used by the individuals identified in the perversion
      files. These were then analyzed to explain why these individuals might have gone
      unnoticed or their actions unreported by the BSA volunteers. 

PMID- 26307035
TI  - Risk Factors for the Development of Psychopathology Following Trauma.

PMID- 26307037
TI  - Obstructive sleep apnoea during REM sleep and incident non-dipping of nocturnal
      blood pressure: a longitudinal analysis of the Wisconsin Sleep Cohort.
AB  - BACKGROUND: Non-dipping of nocturnal blood pressure (BP) is associated with
      target organ damage and cardiovascular disease. Obstructive sleep apnoea (OSA) is
      associated with incident non-dipping. However, the relationship between
      disordered breathing during rapid eye movement (REM) sleep and the risk of
      developing non-dipping has not been examined. This study investigates whether OSA
      during REM sleep is associated with incident non-dipping. METHODS: Our sample
      included 269 adults enrolled in the Wisconsin Sleep Cohort Study who completed
      two or more 24 h ambulatory BP studies over an average of 6.6 years of follow-up.
      After excluding participants with prevalent non-dipping BP or antihypertensive
      use at baseline, there were 199 and 215 participants available for longitudinal
      analysis of systolic and diastolic non-dipping, respectively. OSA in REM and non
      REM sleep were defined by apnoea hypopnoea index (AHI) from baseline in
      laboratory polysomnograms. Systolic and diastolic non-dipping were defined by
      systolic and diastolic sleep/wake BP ratios >0.9. Modified Poisson regression
      models estimated the relative risks for the relationship between REM AHI and
      incident non-dipping, adjusting for non-REM AHI and other covariates. RESULTS:
      There was a dose-response greater risk of developing systolic and diastolic non
      dipping BP with greater severity of OSA in REM sleep (p-trend=0.021 for systolic
      and 0.024 for diastolic non-dipping). Relative to those with REM AHI<1 event/h,
      those with REM AHI>=15 had higher relative risk of incident systolic non-dipping
      (2.84, 95% CI 1.10 to 7.29) and incident diastolic non-dipping (4.27, 95% CI 1.20
      to 15.13). CONCLUSIONS: Our findings indicate that in a population-based sample,
      REM OSA is independently associated with incident non-dipping of BP.

PMID- 26307036
TI  - Immune cell subsets and their gene expression profiles from human PBMC isolated
      by Vacutainer Cell Preparation Tube (CPTTM) and standard density gradient.
AB  - BACKGROUND: High quality genetic material is an essential pre-requisite when
      analyzing gene expression using microarray technology. Peripheral blood
      mononuclear cells (PBMC) are frequently used for genomic analyses, but several
      factors can affect the integrity of nucleic acids prior to their extraction,
      including the methods of PBMC collection and isolation. Due to the lack of the
      relevant data published, we compared the Ficoll-Paque density gradient
      centrifugation and BD Vacutainer cell preparation tube (CPT) protocols to
      determine if either method offered a distinct advantage in preparation of PBMC
      derived immune cell subsets for their use in gene expression analysis. We
      evaluated the yield and purity of immune cell subpopulations isolated from PBMC
      derived by both methods, the quantity and quality of extracted nucleic acids, and
      compared gene expression in PBMC and individual immune cell types from Ficoll and
      CPT isolation protocols using Affymetrix microarrays. RESULTS: The mean yield and
      viability of fresh PBMC acquired by the CPT method (1.16 * 10(6) cells/ml, 93.3%)
      were compatible to those obtained with Ficoll (1.34 * 10(6) cells/ml, 97.2%). No
      differences in the mean purity, recovery, and viability of CD19+ (B cells), CD8+
      (cytotoxic T cells), CD4+ (helper T cell) and CD14+ (monocytes) positively
      selected from CPT- or Ficoll-isolated PBMC were found. Similar quantities of high
      quality RNA and DNA were extracted from PBMC and immune cells obtained by both
      methods. Finally, the PBMC isolation methods tested did not impact subsequent
      recovery and purity of individual immune cell subsets and, importantly, their
      gene expression profiles. CONCLUSIONS: Our findings demonstrate that the CPT and
      Ficoll PBMC isolation protocols do not differ in their ability to purify high
      quality immune cell subpopulations. Since there was no difference in the gene
      expression profiles between immune cells obtained by these two methods, the
      Ficoll isolation can be substituted by the CPT protocol without conceding
      phenotypic changes of immune cells and compromising the gene expression studies.
      Given that the CPT protocol is less elaborate, minimizes cells' handling and
      processing time, this method offers a significant operating advantage, especially
      in large-scale clinical studies aiming at dissecting gene expression in PBMC and
      PBMC-derived immune cell subpopulations.

PMID- 26307038
TI  - Comparison of the prognosis and recurrence of apparent early-stage ovarian tumors
      treated with laparoscopy and laparotomy: a meta-analysis of clinical studies.
AB  - BACKGROUND: This meta-analysis aimed to evaluate the prognosis and recurrence of
      apparent early-stage ovarian tumors treated with laparoscopy compared with
      laparotomy. METHODS: Clinical studies published in English were retrieved from
      the computerized databases Medline and Embase. A meta-analysis was performed to
      investigate the differences in the efficacy and safety of laparoscopy versus
      laparotomy in terms of postoperative complications, lengths of hospital stay,
      recurrence rates, and disease-free survival times using the random effects model.
      The studies were independently reviewed by two investigators. Data from the
      eligible studies were extracted, and the meta-analysis was performed using the
      Comprehensive Meta-Analysis program, version 2 (CMA-2; Biostat, Englewood, NJ,
      USA). RESULTS: A total of 8 studies were included in the analysis. The results
      showed that laparoscopic surgery was significantly associated with lower rates of
      complications (OR = 0.433, P = 0.019) and shorter postoperative hospital stays
      (weighted mean difference [WMD] = -0.974, P < 0.001). There was no significant
      difference in the rates of recurrence (OR = 0.707, P = 0.521) between patients
      with apparent early-stage ovarian tumors who were treated using laparoscopy and
      those who underwent laparotomy. No publication bias was detected. CONCLUSIONS:
      Laparoscopic surgery shows favorable prognostic outcomes in terms of
      postoperative complication rates and postoperative hospital stay durations.
      Further studies with longer follow-up periods are required to confirm recurrence
      and survival outcomes after laparoscopic surgery in patients with apparent early
      stage ovarian tumors.

PMID- 26307039
TI  - Targeting Head and Neck Cancer Stem Cells: Current Advances and Future
      Challenges.
AB  - Cancer stem cells (CSCs), or tumor-initiating cells, comprise a subset of tumor
      cells with demonstrated ability for tumor growth, invasion, metastasis, and
      resistance to chemotherapy and radiation. Targeting of CSCs remains an attractive
      yet elusive therapeutic option, with the goal of increasing specificity and
      effectiveness in tumor eradication, as well as decreasing off-target or systemic
      toxicity. Research into further characterization and targeted therapy toward head
      and neck CSCs is an active and rapidly evolving field. This review discusses the
      current state of research into therapy against head and neck CSCs and future
      directions for targeted therapy. 

PMID- 26307042
TI  - A parasitic plant increases native and exotic plant species richness in vernal
      pools.
AB  - Species interactions are well known to affect species diversity in communities,
      but the effects of parasites have been less studied. Previous studies on
      parasitic plants have found both positive and negative effects on plant community
      diversity. Cuscuta howelliana is an abundant endemic parasitic plant that
      inhabits California vernal pools. We tested the hypothesis that C. howelliana
      acts as a keystone species to increase plant species richness in vernal pools
      through a C. howelliana removal experiment at Beale Air Force Base in north
      central California. Vernal pool endemic plants were parasitized more frequently,
      and Eryngium castrense and Navarretia leucocephala were the most frequently
      parasitized host plant species of C. howelliana. Cuscuta howelliana caused higher
      plant species richness, both natives and exotics, compared with removal plots.
      However, there was no single plant species that significantly increased with C.
      howelliana removal. Decreases in Eryngium castrense percent cover plots with C.
      howelliana is a plausible explanation for differences in species richness. In
      conclusion, C. howelliana led to changes in species composition and increases in
      plant species richness, consistent with what is expected from the effects of a
      keystone species. This research provides support for a shift in management
      strategies that focus on species-specific targets to strategies that target
      maintenance of complex species interactions and therefore maximize biodiversity
      and resilience of ecosystems. 

PMID- 26307040
TI  - Anaesthetist-provided pre-hospital advanced airway management in children: a
      descriptive study.
AB  - BACKGROUND: Pre-hospital advanced airway management has been named one of the top
      five research priorities in physician-provided pre-hospital critical care. Few
      studies have been made on paediatric pre-hospital advanced airway management. The
      aim of this study was to investigate pre-hospital endotracheal intubation success
      rate in children, first-pass success rates and complications related to pre
      hospital advanced airway management in patients younger than 16 years of age
      treated by pre-hospital critical care teams in the Central Denmark Region (1.3
      million inhabitants). METHODS: A prospective descriptive study based on data
      collected from eight anaesthetist-staffed pre-hospital critical care teams
      between February 1st 2011 and November 1st 2012. Primary endpoints were 1) pre
      hospital endotracheal intubation success rate in children 2) pre-hospital
      endotracheal intubation first-pass success rate in children and 3) complications
      related to prehospital advanced airway management in children. RESULTS: The pre
      hospital critical care anaesthetists attempted endotracheal intubation in 25
      children, 13 of which were less than 2 years old. In one patient, a neonate (600
      g birth weight), endotracheal intubation failed. The patient was managed by
      uneventful bag-mask ventilation. All other 24 children had their tracheas
      successfully intubated by the pre-hospital critical care anaesthetists resulting
      in a pre-hospital endotracheal intubation success rate of 96 %. Overall first
      pass success-rate was 75 %. In the group of patients younger than 2 years old,
      first pass success-rate was 54 %. The total rate of airway management related
      complications such as vomiting, aspiration, accidental intubation of the
      oesophagus or right main stem bronchus, hypoxia (oxygen saturation < 90 %) or
      bradycardia (according to age) was 20 % in children younger than 16 years of age
      and 38 % in children younger than 2 years of age. No deaths, cardiac arrests or
      severe bradycardia (heart rate <60) occurred in relation to pre-hospital advanced
      airway management. CONCLUSION: Compared with the total population of patients
      receiving pre-hospital advanced airway management in our system, the overall
      success rate following pre-hospital endotracheal intubations in children is
      acceptable but the first-pass success rate is low. The complication rates in the
      paediatric population are higher than in our pre-hospital advanced airway
      management patient population as a whole. This illustrates that young children
      may represent a substantial pre-hospital airway management challenge even for
      experienced pre-hospital critical care anaesthetists. This may influence future
      training and quality insurance initiatives in paediatric pre-hospital advanced
      airway management.

PMID- 26307043
TI  - Integrating Levels of Analysis in Systems and Cognitive Neurosciences: Selective
      Attention as a Case Study.
AB  - Neuroscience is inherently interdisciplinary, rapidly expanding beyond its roots
      in biological sciences to many areas of the social and physical sciences. This
      expansion has led to more sophisticated ways of thinking about the links between
      brains and behavior and has inspired the development of increasingly advanced
      tools to characterize the activity of large populations of neurons. However,
      along with these advances comes a heightened risk of fostering confusion unless
      efforts are made to better integrate findings across different model systems and
      to develop a better understanding about how different measurement techniques
      provide mutually constraining information. Here we use selective visuospatial
      attention as a case study to highlight the importance of these issues, and we
      suggest that exploiting multiple measures can better constrain models that relate
      neural activity to animal behavior.

PMID- 26307044
TI  - Nosocomial exposure to active pulmonary tuberculosis in a neonatal intensive care
      unit.
AB  - BACKGROUND: Nosocomial transmission of tuberculosis (TB) in a neonatal intensive
      care unit (NICU) is a recognized risk. We investigated TB transmission to
      neonates and health care workers (HCWs) exposed to a nurse with active TB in a
      NICU. METHODS: A NICU nurse in a tertiary referral hospital in Seoul, Korea,
      developed pulmonary TB. The investigation included 108 infants and 75 HCWs.
      Tuberculin skin test (TST) and chest radiograph were performed at baseline.
      Isoniazid prophylaxis was started in neonates. After 3 months of prophylaxis,
      infants underwent repeat TST and chest radiograph. HCWs underwent a second TST
      after 3 months. RESULTS: Baseline chest radiographs were negative in infants and
      HCWs. Four (3.7%) of 108 infants screened had a positive TST, including 2
      conversions, and received isoniazid for 6-9 months. Among the 59 HCWs screened,
      27 (45.8%) had an initial positive TST result, and 6 (10.2%) had a positive TST
      result at 3 months. Four of the 6 HCWs with TST conversions received isoniazid
      treatment for 9 months. In the 2-year period after exposure, none of the exposed
      infants or HCWs developed active TB. CONCLUSION: In this investigation, 4 (3.7%)
      of 108 infants exposed to a nurse with active TB developed latent TB infection.
      They were given isoniazid therapy without any adverse events and did not progress
      to TB disease in the 2 years after exposure.

PMID- 26307045
TI  - Prevention of central venous catheter-associated bloodstream infections: A
      questionnaire evaluating the knowledge of the selected 11 evidence-based
      guidelines by Polish nurses.
AB  - This study evaluated the questionnaire testing nurses' knowledge about the
      maintenance of a central venous catheter (CVC) and assessed it with regard to
      age, work experience, type of ward, frequency of trainings, and postgraduate
      education. There were 1,180 questionnaires (N = 784; 66.4% of the total sample)
      distributed in several regions of Poland for a period of 7 months. The difficulty
      level for each question ranged from 0.22-0.88.

PMID- 26307047
TI  - An evaluation of psychological distress and social support of survivors and
      contacts of Ebola virus disease infection and their relatives in Lagos, Nigeria:
      a cross sectional study--2014.
AB  - BACKGROUND: By September 2014, an outbreak of Ebola Viral Disease (EVD) in West
      African countries of Guinea, Liberia, Sierra Leone, Senegal and Nigeria, had
      recorded over 4500 and 2200 probable or confirmed cases and deaths respectively.
      EVD, an emerging infectious disease, can create fear and panic among patients,
      contacts and relatives, which could be a risk factor for psychological distress.
      Psychological distress among this subgroup could have public health implication
      for control of EVD, because of potential effects on patient management and
      contact tracing. We determined the Prevalence, pattern and factors associated
      with psychological distress among survivors and contacts of EVD and their
      relatives. METHODS: In a descriptive cross sectional study, we used General
      Health Questionnaire to assess psychological distress and Oslo Social Support
      Scale to assess social support among 117 participants who survived EVD, listed as
      EVD contacts or their relatives at Ebola Emergency Operation Center in Lagos,
      Nigeria. Factors associated with psychological distress were determined using chi
      square/odds ratio and adjusted odds ratio. RESULTS: The mean age and standard
      deviation of participants was 34 +/ - 9.6 years. Of 117 participants, 78 (66.7%)
      were females, 77 (65.8%) had a tertiary education and 45 (38.5%) were health
      workers. Most frequently occurring psychological distress were inability to
      concentrate (37.6%) and loss of sleep over worry (33.3%). Losing a relation to
      EVD outbreak (OR = 6.0, 95% CI, 1.2-32.9) was significantly associated with
      feeling unhappy or depressed while being a health worker was protective (OR =
      0.4, 95% CI, 0.2-0.9). Adjusted Odds Ratio (AOR) showed losing a relation (AOR =
      5.7, 95% CI, 1.2-28.0) was a predictor of "feeling unhappy or depressed", loss of
      a relation (AOR = 10.1, 95% CI, 1.7-60.7) was a predictor of inability to
      concentrate. CONCLUSIONS: Survivors and contacts of EVD and their relations
      develop psychological distress. Development of psychological distress could be
      predicted by loss of family member. It is recommended that psychiatrists and
      other mental health specialists be part of case management teams. The clinical
      teams managing EVD patients should be trained on recognition of common
      psychological distress among patients. A mental health specialist should review
      contacts being monitored for EVD for psychological distress or disorders.

PMID- 26307048
TI  - Using the Technology Acceptance Model to explore community dwelling older adults'
      perceptions of a 3D interior design application to facilitate pre-discharge home
      adaptations.
AB  - BACKGROUND: In the UK occupational therapy pre-discharge home visits are
      routinely carried out as a means of facilitating safe transfer from the hospital
      to home. Whilst they are an integral part of practice, there is little evidence
      to demonstrate they have a positive outcome on the discharge process. Current
      issues for patients are around the speed of home visits and the lack of shared
      decision making in the process, resulting in less than 50 % of the specialist
      equipment installed actually being used by patients on follow-up. To improve
      practice there is an urgent need to examine other ways of conducting home visits
      to facilitate safe discharge. We believe that Computerised 3D Interior Design
      Applications (CIDAs) could be a means to support more efficient, effective and
      collaborative practice. A previous study explored practitioners perceptions of
      using CIDAs; however it is important to ascertain older adult's views about the
      usability of technology and to compare findings. This study explores the
      perceptions of community dwelling older adults with regards to adopting and using
      CIDAs as an assistive tool for the home adaptations process. METHODS: Ten
      community dwelling older adults participated in individual interactive task
      focused usability sessions with a customised CIDA, utilising the think-aloud
      protocol and individual semi-structured interviews. Template analysis was used to
      carry out both deductive and inductive analysis of the think-aloud and interview
      data. Initially, a deductive stance was adopted, using the three pre-determined
      high-level themes of the technology acceptance model (TAM): Perceived Usefulness
      (PU), Perceived Ease of Use (PEOU), Actual Use (AU). Inductive template analysis
      was then carried out on the data within these themes, from which a number of sub
      thmes emerged. RESULTS: Regarding PU, participants believed CIDAs served as a
      useful visual tool and saw clear potential to facilitate shared understanding and
      partnership in care delivery. For PEOU, participants were able to create 3D home
      environments however a number of usability issues must still be addressed. The AU
      theme revealed the most likely usage scenario would be collaborative involving
      both patient and practitioner, as many participants did not feel confident or see
      sufficient value in using the application autonomously. CONCLUSIONS: This
      research found that older adults perceived that CIDAs were likely to serve as a
      valuable tool which facilitates and enhances levels of patient/practitioner
      collaboration and empowerment. Older adults also suggested a redesign of the
      interface so that less sophisticated dexterity and motor functions are required.
      However, older adults were not confident, or did not see sufficient value in
      using the application autonomously. Future research is needed to further
      customise the CIDA software, in line with the outcomes of this study, and to
      explore the potential of collaborative application patient/practitioner-based
      deployment.

PMID- 26307049
TI  - Chronic hepatitis E infection with an emerging virus strain in a heart transplant
      recipient successfully treated with ribavirin: a case report.
AB  - INTRODUCTION: During the last decade hepatitis E infections have been recognized
      as a health problem in high-income countries, where hepatitis E virus genotype 3
      is endemic. The infection is often self-limiting, but may develop into chronic
      infection in immunocompromised patients, especially in solid organ recipients. If
      these patients or patients with underlying liver disease get hepatitis E
      infection, they may develop liver failure and cirrhosis. Hepatitis E virus is
      occasionally found in blood products and transfusion transmission has been
      reported. We present the first case of chronic hepatitis E infection in a heart
      transplant recipient in Sweden. CASE PRESENTATION: A 63-year-old Swedish white
      man presented with highly elevated liver enzymes 6 months after heart
      transplantation. Polymerase chain reaction revealed chronic hepatitis E
      infection, caused by a virus strain found infecting symptomatic cases in Sweden
      and other European countries. During transplantation, he received blood products
      from 17 donors, and transfusion transmission is highly likely. The only
      detectable marker for hepatitis E infection was hepatitis E virus ribonucleic
      acid for more than 2 months before anti-hepatitis E virus developed. He was
      treated successfully with ribavirin and decreased immunosuppression. CONCLUSIONS:
      Our patient was probably infected through contaminated blood products and
      subsequently developed chronic infection, which was cured upon treatment. This
      highlights the need for evaluating the problem with chronic hepatitis E infection
      in immunocompromised patients, and for discussion concerning screening of blood
      products. Polymerase chain reaction-based methods are recommended for diagnosing
      hepatitis E infection in patients with compromised immunity. In addition,
      knowledge needs to be gained on the infecting virus strain, which may be more
      virulent than other strains.

PMID- 26307051
TI  - Heterogeneity revealed through meta-analysis might link geographical differences
      with nasopharyngeal carcinoma incidence in Han Chinese populations.
AB  - BACKGROUND: Nasopharyngeal carcinoma (NPC) is an epithelial malignancy highly
      prevalent in southern China, and incidence rates among Han Chinese people vary
      according to geographic region. Recently, three independent genome-wide
      association studies (GWASs) confirmed that HLA-A is the main risk gene for NPC.
      However, the results of studies conducted in regions with dissimilar incidence
      rates contradicted the claims that HLA-A is the sole risk gene and that the
      association of rs29232 is independent of the HLA-A effect in the chromosome
      6p21.3 region. METHODS: We performed a meta-analysis, selecting five single
      nucleotide polymorphisms (SNPs) in chromosome 6p21.3 mapped in three published
      GWASs and four case-control studies. The studies involved 8994 patients with NPC
      and 11,157 healthy controls, all of whom were Han Chinese. RESULTS: The rs2517713
      SNP located downstream of HLA-A was significantly associated with NPC (P = 1.08 *
      10(-91), odds ratio [OR] = 0.58, 95 % confidence interval [CI] = 0.55-0.61). The
      rs29232 SNP exhibited a moderate level of heterogeneity (I(2) = 47 %) that
      disappeared (I(2) = 0 %) after stratification by moderate- and high-incidence NPC
      regions. CONCLUSIONS: Our results suggested that the HLA-A gene is strongly
      associated with NPC risk. In addition, the heterogeneity revealed by the meta
      analysis of rs29232 might be associated with regional differences in NPC
      incidence among Han Chinese people. The higher OR of rs29232 and the fact that
      rs29232 was independent of the HLA-A effect in the moderate-incidence population
      suggested that rs29232 might have greater relevance to NPC incidence in a
      moderate-incidence population than in a high-incidence population.

PMID- 26307050
TI  - Intracytoplasmic morphologically selected sperm injection versus conventional
      intracytoplasmic sperm injection: a randomized controlled trial.
AB  - BACKGROUND: Intracytoplasmic morphologically selected sperm injection (IMSI) is
      still proposed and employed in the clinical practice to improve the reproductive
      outcome in infertile couples scheduled for conventional intracytoplasmic sperm
      injection (cICSI). The aim of the current randomized controlled trial (RCT) was
      to test the hypothesis that IMSI gives a better live birth delivery rate than
      cICSI. METHODS: Infertile couples scheduled for their first cICSI cycle for male
      factor were allocated using a simple randomization procedure. All available
      biological and clinical data were recorded and analyzed in a triple-blind
      fashion. RESULTS: Our final analysis involved the first 121 patients (48 and 73
      subjects for IMSI and cICSI arm, respectively) because the trial was stopped
      prematurely on the advice of the data safety and monitoring Committee because of
      concerns about IMSI efficacy at the first interim analysis. No significant
      difference between arms was detected in rates of clinical pregnancy per embryo
      transferred [11/34 (32.3%) vs. 15/64 (23.4%); odds ratio (OR) 1.56, 95%
      (confidence interval) CI 0.62-3.93, P = 0.343] and of live birth delivery [9/48
      (18.8%) vs. 11/73 (15.1%); OR 1.30, 95%CI 0.49-3.42, P = 0.594). CONCLUSION:
      Current data did not support the routine use of IMSI in the clinical practice for
      improving cICSI results in unselected infertile couples with male factor.

PMID- 26307052
TI  - The impact of cigarette smoking on life expectancy between 1980 and 2010: a
      global perspective.
AB  - INTRODUCTION: Tobacco smoking is among the leading causes of preventable
      mortality worldwide. We assessed the impact of smoking on life expectancy
      worldwide between 1980 and 2010. METHODS: We retrieved cause-specific mortality
      data from the WHO Mortality Database by sex, year and age for 63 countries with
      high or moderate quality data (1980-2010). Using the time of the peak of the
      smoking epidemic by country, relative risks from the three waves of the Cancer
      Prevention Study were applied to calculate the smoking impact ratio and
      population attributable fraction. Finally, we estimated the potential gain in
      life expectancy at age 40 if smoking-related deaths in middle age (40-79 years)
      were eliminated. RESULTS: Currently, tobacco smoking is related to approximately
      20% of total adult mortality in the countries in this study (24% in men and 12%
      in women). If smoking-related deaths were eliminated, adult life expectancy would
      increase on average by 2.4 years in men (0.1 in Uzbekistan to 4.8 years in
      Hungary) and 1 year in women (0.1 in Kyrgyzstan to 2.9 years in the USA). The
      proportion of smoking-related mortality among men has declined in most countries,
      but has increased in the most populous country in the world, that is, China from
      4.6% to 7.3%. Increases in the impact of tobacco on life expectancy were observed
      among women in high-income countries. CONCLUSIONS: Recent trends indicate a
      substantial rise in the population-level impact of tobacco smoking on life
      expectancy in women and in middle-income countries. High-quality local data are
      needed in most low-income countries.

PMID- 26307053
TI  - Left-sided partial anomalous pulmonary venous return in a septuagenarian.

PMID- 26307054
TI  - Angina in left main coronary artery occlusion by pulmonary artery aneurysm.
AB  - A 51-year-old woman with exercise angina and a history of pulmonary artery
      hypertension related to a previous pulmonary thromboembolism, was referred to our
      hospital. Computed tomography and coronary angiography showed a 95-mm aneurysm of
      the main pulmonary artery, which totally occluded the left main coronary artery.
      After a multidisciplinary evaluation, we recommended heart-lung transplantation,
      but the patient refused any kind of surgical procedure. Due to the chronic
      occlusion, stenting of the left main coronary artery was unfeasible. With no
      other options available, we could only start pulmonary antihypertensive therapy.
      At the 1-year follow-up, the patient reported relief of her angina.

PMID- 26307056
TI  - User interface design for mobile-based sexual health interventions for young
      people: design recommendations from a qualitative study on an online Chlamydia
      clinical care pathway.
AB  - BACKGROUND: The increasing pervasiveness of mobile technologies has given
      potential to transform healthcare by facilitating clinical management using
      software applications. These technologies may provide valuable tools in sexual
      health care and potentially overcome existing practical and cultural barriers to
      routine testing for sexually transmitted infections. In order to inform the
      design of a mobile health application for STIs that supports self-testing and
      self-management by linking diagnosis with online care pathways, we aimed to
      identify the dimensions and range of preferences for user interface design
      features among young people. METHODS: Nine focus group discussions were conducted
      (n = 49) with two age-stratified samples (16 to 18 and 19 to 24 year olds) of
      young people from Further Education colleges and Higher Education establishments.
      Discussions explored young people's views with regard to: the software interface;
      the presentation of information; and the ordering of interaction steps.
      Discussions were audio recorded and transcribed verbatim. Interview transcripts
      were analysed using thematic analysis. RESULTS: Four over-arching themes emerged:
      privacy and security; credibility; user journey support; and the task-technology
      context fit. From these themes, 20 user interface design recommendations for
      mobile health applications are proposed. For participants, although privacy was a
      major concern, security was not perceived as a major potential barrier as
      participants were generally unaware of potential security threats and inherently
      trusted new technology. Customisation also emerged as a key design preference to
      increase attractiveness and acceptability. CONCLUSIONS: Considerable effort
      should be focused on designing healthcare applications from the patient's
      perspective to maximise acceptability. The design recommendations proposed in
      this paper provide a valuable point of reference for the health design community
      to inform development of mobile-based health interventions for the diagnosis and
      treatment of a number of other conditions for this target group, while
      stimulating conversation across multidisciplinary communities.

PMID- 26307057
TI  - Increasing incidence of non-valvular atrial fibrillation in the UK from 2001 to
      2013.
AB  - OBJECTIVE: To determine whether the incidence of atrial fibrillation (AF) is
      static or rising in the UK. DESIGN: Among the cohort of all individuals aged >=45
      years in the UK Clinical Practice Research Datalink (CPRD) (linked to hospital
      discharges) we identified incident non-valvular AF cases between 2001 and 2013.
      Overall and annual AF incidence rates were calculated and standardised to the UK
      population. RESULTS: The cohort of 2.23 million individuals included 91,707
      patients with incident AF. The overall standardised AF incidence rate was 6.7
      (95% CI 6.7 to 6.8) per 1000 person-years, increasing exponentially with age and
      higher in men of all ages. There was a small increase in the standardised
      incidence of AF in the last decade from 5.9 (5.8 to 6.1)/1000 person-years in
      2001 to 6.9 (6.8 to 7.1)/1000 person-years in 2013, mostly attributable to
      subjects aged >80 years with a non-primary hospital discharge diagnosis of AF.
      Standardised incidence rates of AF among white patients was 8.1 (8.1 to 8.2)/1000
      person-years, compared with 5.4 (4.6 to 6.3) for Asians and 4.6 (4.0 to 5.3) for
      black patients. AF diagnosis was first made in general practice in 39% of
      incident AF. CONCLUSIONS: The incidence of AF in the UK has increased gradually
      in the last decade, with more than 200 000 first-ever non-valvular AF cases
      expected in 2015. This increase is only partly due to population ageing, though
      the principal increase has been in the elderly hospitalised for a reason other
      than AF.

PMID- 26307055
TI  - A systematic review and meta-analysis of the effectiveness of food safety
      education interventions for consumers in developed countries.
AB  - BACKGROUND: Foodborne illness has a large public health and economic burden
      worldwide, and many cases are associated with food handled and prepared at home.
      Educational interventions are necessary to improve consumer food safety practices
      and reduce the associated burden of foodborne illness. METHODS: We conducted a
      systematic review and targeted meta-analyses to investigate the effectiveness of
      food safety education interventions for consumers. Relevant articles were
      identified through a preliminary scoping review that included: a comprehensive
      search in 10 bibliographic databases with verification; relevance screening of
      abstracts; and extraction of article characteristics. Experimental studies
      conducted in developed countries were prioritized for risk-of-bias assessment and
      data extraction. Meta-analysis was conducted on data subgroups stratified by key
      study design-intervention-population-outcome categories and subgroups were
      assessed for their quality of evidence. Meta-regression was conducted where
      appropriate to identify possible sources of between-trial heterogeneity. RESULTS:
      We identified 79 relevant studies: 17 randomized controlled trials (RCTs); 12 non
      randomized controlled trials (NRTs); and 50 uncontrolled before-and-after
      studies. Several studies did not provide sufficient details on key design
      features (e.g. blinding), with some high risk-of-bias ratings due to incomplete
      outcome data and selective reporting. We identified a moderate to high confidence
      in results from two large RCTs investigating community- and school-based
      educational training interventions on behaviour outcomes in children and youth
      (median standardized mean difference [SMD] = 0.20, range: 0.05, 0.35); in two
      small RCTs evaluating video and written instructional messaging on behavioural
      intentions in adults (SMD = 0.36, 95% confidence interval [CI]: 0.02, 0.69); and
      in two NRT studies for university-based education on attitudes of students and
      staff (SMD = 0.26, 95% CI: 0.10, 0.43). Uncontrolled before-and-after study
      outcomes were very heterogeneous and we have little confidence that the meta
      analysis results reflect the true effect. Some variation in outcomes was
      explained in meta-regression models, including a dose effect for behaviour
      outcomes in RCTs. CONCLUSIONS: In controlled trials, food safety education
      interventions showed significant effects in some contexts; however, many outcomes
      were very heterogeneous and do not provide a strong quality of evidence to
      support decision-making. Future research in this area is needed using more robust
      experimental designs to build on interventions shown to be effective in
      uncontrolled before-and-after studies.

PMID- 26307058
TI  - Application of fractional flow reserve and optical coherence tomography
      examinations in a patient presenting with recurrent angina: a case report.
AB  - INTRODUCTION: We present the different roles of fractional flow reserve and
      optical coherence tomography in guiding treatment in a patient with recurrent
      chest pain. CASE PRESENTATION: A 66-year-old Chinese woman presented to our
      department for the third time for her recurrent chest pain. Her physical
      examination was unremarkable; her previous two angiography examinations indicated
      that there was a stenosis of 50 to 70% in her proximal left anterior descending
      coronary artery. Optimal medical therapy was applied, but her symptoms did not
      disappear. Coronary angiography was conducted again after admission, accompanied
      by fractional flow reserve and optical coherence tomography. A lesion of 50 to
      70% in her left anterior descending coronary artery was detected in an angiogram
      as before; her fractional flow reserve measure was a negative result of 0.88.
      However, a plaque rupture was found at the location of the lesion in the optical
      coherence tomography imaging. A stent was implanted in her left anterior
      descending coronary artery; she made no complaint of chest pain during follow-up
      of 1.5 years after her discharge. CONCLUSIONS: Fractional flow reserve is
      considered the "gold standard" to detect ischemia-causing lesions and provide
      hemodynamic information of a stenosis. However, lack of structural information of
      a stenosis limits the application of fractional flow reserve and coronary
      pressure may lie sometimes. We should choose the best strategy for patients
      according to different examinations and patients' symptoms, never a single test.

PMID- 26307059
TI  - Identification of non-essential loci within the Meleagrid herpesvirus 1 genome.
AB  - BACKGROUND: Meleagrid herpesvirus 1 (MeHV-1) infectious bacterial artificial
      chromosomes (iBACs) are ideal vectors for the development of recombinant vaccines
      for the poultry industry. However, the full potential of iBACS as vectors can
      only be realised after thorough genetic characterisation, including
      identification of those genetic locations that are non-essential for virus
      replication. Generally, transposition has proven to be a highly effective
      strategy for rapid and efficient mutagenesis of iBAC clones. The current study
      describes the characterisation of 34 MeHV-1 mutants containing transposon
      insertions within the pMeHV1-C18 iBAC genome. METHODS: Tn5 and MuA transposition
      methods were used to generate a library of 76 MeHV-1 insertion mutants. The
      capacity of each mutant to facilitate the recovery of infectious MeHV-1 was
      determined by the transfection of clone DNA into chicken embryo fibroblasts.
      RESULTS: Attempts to recover infectious virus from the modified clones identified
      14 genetic locations that were essential for MeHV-1 replication in cell culture.
      Infectious MeHV-1 was recovered from the remaining 14 intragenic insertion
      mutants and six intergenic insertion mutants, suggesting that the respective
      insertion locations are non-essential for MeHV-1 replication in cell culture.
      CONCLUSIONS: The essential and non-essential designations for those MeHV-1 genes
      characterised in this study were generally in agreement with previous reports for
      other herpesviruses homologues. However, the requirement for the mardivirus
      specific genes LORF4A and LORF5 are reported for the first time. These findings
      will help direct future work on the development of recombinant poultry vaccines
      using MeHV-1 as a vector by identifying potential transgene insertion sites
      within the viral genome.

PMID- 26307060
TI  - Adequate antibiotic therapy prior to ICU admission in patients with severe sepsis
      and septic shock reduces hospital mortality.
AB  - INTRODUCTION: In patients with severe sepsis and septic shock as cause of
      Intensive Care Unit (ICU) admission, we analyze the impact on mortality of
      adequate antimicrobial therapy initiated before ICU admission. METHODS: We
      conducted a prospective observational study enrolling patients admitted to the
      ICU with severe sepsis or septic shock from January 2008 to September 2013. The
      primary end-point was in-hospital mortality. We considered two groups for
      comparisons: patients who received adequate antibiotic treatment before or after
      the admission to the ICU. RESULTS: A total of 926 septic patients were admitted
      to ICU, and 638 (68.8%) had available microbiological isolation: 444 (69.6%)
      received adequate empirical antimicrobial treatment prior to ICU and 194 (30.4%)
      after admission. Global hospital mortality in patients that received treatment
      before ICU admission, between 0-6h ICU, 6-12h ICU, 12-24h ICU and after 24 hours
      since ICU admission were 31.3, 53.2, 57.1, 50 and 50.8% (p<0.001). The
      multivariate analysis showed that urinary focus (odds ratio (OR) 0.20; 0.09-0.42;
      p<0.001) and adequate treatment prior to ICU admission (OR 0.37; 0.24-0.56;
      p<0.001) were protective factors whereas APACHE II score (OR 1.10; 1.07-1.14;
      p<0.001), septic shock (OR 2.47; 1.57-3.87; p<0.001), respiratory source (OR
      1.91; 1.12-3.21; p=0.016), cirrhosis (OR 3.74; 1.60-8.76; p=0.002) and malignancy
      (OR 1.65; 1.02-2.70; p=0.042) were variables independently associated with in
      hospital mortality. Adequate treatment prior to ICU was a protective factor for
      mortality in patients with severe sepsis (n=236) or in septic shock (n=402).
      CONCLUSIONS: The administration of adequate antimicrobial therapy before ICU
      admission is decisive for the survival of patients with severe sepsis and septic
      shock. Our efforts should be directed to assure the correct administration
      antibiotics before ICU admission in patients with sepsis.

PMID- 26307061
TI  - Advances in computational approaches for prioritizing driver mutations and
      significantly mutated genes in cancer genomes.
AB  - Cancer is often driven by the accumulation of genetic alterations, including
      single nucleotide variants, small insertions or deletions, gene fusions, copy
      number variations, and large chromosomal rearrangements. Recent advances in next
      generation sequencing technologies have helped investigators generate massive
      amounts of cancer genomic data and catalog somatic mutations in both common and
      rare cancer types. So far, the somatic mutation landscapes and signatures of >10
      major cancer types have been reported; however, pinpointing driver mutations and
      cancer genes from millions of available cancer somatic mutations remains a
      monumental challenge. To tackle this important task, many methods and
      computational tools have been developed during the past several years and, thus,
      a review of its advances is urgently needed. Here, we first summarize the main
      features of these methods and tools for whole-exome, whole-genome and whole
      transcriptome sequencing data. Then, we discuss major challenges like tumor intra
      heterogeneity, tumor sample saturation and functionality of synonymous mutations
      in cancer, all of which may result in false-positive discoveries. Finally, we
      highlight new directions in studying regulatory roles of noncoding somatic
      mutations and quantitatively measuring circulating tumor DNA in cancer. This
      review may help investigators find an appropriate tool for detecting potential
      driver or actionable mutations in rapidly emerging precision cancer medicine.

PMID- 26307063
TI  - Endometrioid adenocarcinoma of the ovary: MRI findings with emphasis on diffusion
      weighted imaging for the differentiation of ovarian tumors.
AB  - BACKGROUND: Preoperative differentiation of ovarian malignant tumors still
      remains a challenge. Diffusion-weighted imaging (DWI) provides information about
      cellularity of the lesion and might facilitate discrimination between different
      malignant ovarian lesions. PURPOSE: To evaluate magnetic resonance imaging (MRI)
      findings of endometrioid adenocarcinoma of the ovary and to determine the value
      of DWI in the differential diagnosis of malignant and benign adnexal tumors.
      MATERIAL AND METHODS: The following MRI findings were reviewed in 162 patients
      (21 endometrioid adenocarcinoma, 103 other malignant tumors, 38 benign tumors):
      lesion size, morphological appearance, T2-weighted (T2W) signal intensity, T1
      weighted (T1W) signal intensity, contrast-enhancement pattern, DWI signals with
      apparent diffusion coefficient (ADC) calculated for b = 800 s/mm(2) in solid
      tumor components. RESULTS: The most common morphological appearance was
      predominantly cystic lesion, found in 90.3% of patients with endometriod
      adenocarcinoma. The solid parts were slightly hyperintense on T2W images in 19
      patients with marked enhancement after contrast administration. No significant
      difference (P = 0.13) in conventional MRI features was found between endometrioid
      adenocarcinoma and other malignant ovarian tumors. Hyperintensity on DWI was more
      frequently observed in malignant tumors than in benign lesions (P < 0.001). ADC
      values were significantly lower in endometrioid adenocarcinoma than other
      malignant tumors (0.79 +/- 0.21 vs. 0.90 +/- 0.19; P = 0.04) and in all malignant
      lesions compared with benign tumors (0.88 +/- 0.31 vs. 1.33 +/- 0.17; P < 0.001).
      CONCLUSION: DWI with ADC measurement could indicate the presence of endometrioid
      adenocarcinomas due to a slightly but significantly lower ADC values compared to
      other malignant ovarian lesions. Thus, DWI is beneficial and should be part of a
      standard protocol for the evaluation of indeterminate adnexal lesions.

PMID- 26307062
TI  - Systems medicine of inflammaging.
AB  - Systems Medicine (SM) can be defined as an extension of Systems Biology (SB) to
      Clinical-Epidemiological disciplines through a shifting paradigm, starting from a
      cellular, toward a patient centered framework. According to this vision, the
      three pillars of SM are Biomedical hypotheses, experimental data, mainly achieved
      by Omics technologies and tailored computational, statistical and modeling tools.
      The three SM pillars are highly interconnected, and their balancing is crucial.
      Despite the great technological progresses producing huge amount of data (Big
      Data) and impressive computational facilities, the Bio-Medical hypotheses are
      still of primary importance. A paradigmatic example of unifying Bio-Medical
      theory is the concept of Inflammaging. This complex phenotype is involved in a
      large number of pathologies and patho-physiological processes such as aging, age
      related diseases and cancer, all sharing a common inflammatory pathogenesis. This
      Biomedical hypothesis can be mapped into an ecological perspective capable to
      describe by quantitative and predictive models some experimentally observed
      features, such as microenvironment, niche partitioning and phenotype propagation.
      In this article we show how this idea can be supported by computational methods
      useful to successfully integrate, analyze and model large data sets, combining
      cross-sectional and longitudinal information on clinical, environmental and omics
      data of healthy subjects and patients to provide new multidimensional biomarkers
      capable of distinguishing between different pathological conditions, e.g. healthy
      versus unhealthy state, physiological versus pathological aging.

PMID- 26307064
TI  - DRD2 and DRD4 genes related to cognitive deficits in HIV-infected adults who
      abuse alcohol.
AB  - BACKGROUND: HIV-infected individuals continue to experience neurocognitive
      deterioration despite virologically successful treatments. The causes of
      neurocognitive impairment are still unclear. However, several factors have been
      suggested including the role of genetics. There is evidence suggesting that
      neurocognitive impairment is heritable and individual differences in cognition
      are strongly driven by genetic variations. The contribution of genetic variants
      affecting the metabolism and activity of dopamine may influence these individual
      differences. METHODS: The present study explored the relationship between two
      candidate genes (DRD4 and DRD2) and neurocognitive performance in HIV-infected
      adults. A total of 267 HIV-infected adults were genotyped for polymorphisms, DRD4
      48 bp-variable number tandem repeat (VNTR), DRD2 rs6277 and ANKK1 rs1800497. The
      Short Category (SCT), Color Trail (CTT) and Rey-Osterrieth Complex Figure Tests
      (ROCT) were used to measure executive function and memory. RESULTS: Results
      showed significant associations with the SNP rs6277 and impaired executive
      function (odds ratio = 3.3, 95% CI 1.2-2.6; p = 0.004) and cognitive flexibility
      (odds ratio = 1.6, 95% CI 2.0-5.7; p = 0.001). The results were further
      stratified by race and sex and significant results were seen in males (odds ratio
      = 3.5, 95% CI 1.5-5.5; p = 0.008) and in African Americans (odds ratio = 3.1, 95%
      CI 2.3-3.5; p = 0.01). Also, DRD4 VNTR 7-allele was significantly associated with
      executive dysfunction. CONCLUSION: The study shows that genetically determined
      differences in the SNP rs6277 DRD2 gene and DRD4 48 bp VNTR may be risk factors
      for deficits in executive function and cognitive flexibility.

PMID- 26307066
TI  - Quantitative analysis of cranial ultrasonographic periventricular echogenicity in
      relation to early neuromotor development in preterm infants.
AB  - BACKGROUND: Periventricular white matter (WM) hyperechoic flares that do not
      evolve into cystic lesion(s) are frequently encountered on cranial
      ultrasonography (CUS) of preterm infants. Subjective interpretation of its
      presence, however, is challenging and its association with maturation and
      neurodevelopment remains undefined. OBJECTIVES: To determine the relationship
      between quantitative WM echogenicity and postnatal and postmenstrual ages and the
      relationship between quantitative WM echogenicity and neuromotor development at
      term equivalent. METHODS: We measured the mean pixel brightness intensity at the
      frontoparietal and parieto-occipital WM, choroid plexus and calvarium bone on
      sequential neonatal CUS scans of preterm infants born at <34 weeks gestation. The
      relative echogenicity (RE) was derived by dividing the mean WM echogenicity to
      that of the choroid plexus (RE(CP)) or bone (RE(BN)). The Lacey Assessment of the
      Preterm Infant was administered before discharge. RESULTS: 58 preterm infants
      (the mean gestational age 30.6+/-2.3 weeks and the mean birth weight 1211.9+/
      224.7 g) were included. The RE(CP) of the frontoparietal WM decreased
      significantly with advancing postnatal and postmenstrual ages (r=-0.4, p<0.0001).
      The RE(BN) values of the frontoparietal and parieto-occipital WM during
      intermediate and late predischarge CUS studies, respectively, were significantly
      associated with neuromotor status at term (p<0.05). The RE(CP) and RE(BN)
      measured during the first week of life were not associated with neuromotor status
      at term. CONCLUSIONS: Quantitative measurements of the periventricular WM
      echogenicity are feasible in neonatal CUSs of premature infants and may reflect
      microstructural developmental changes. An optimal echogenicity quantification
      technique and its correlation with long-term outcome remain to be determined.

PMID- 26307069
TI  - Evaluation of Customized Prosthesis for Irregularly Formed Tracheostoma After
      Laryngectomy.
AB  - BACKGROUND: After laryngectomy, the tracheostoma forms the functional center for
      breathing and phonation. An occasionally occurring but typical problem can arise
      from an oversized and/or irregularly formed tracheostoma, hampering the temporary
      occlusion necessary for sufficient speech production. As an alternative to a
      surgical correction of the tracheostoma, an individually adjusted stoma silicone
      prosthesis may be used. MATERIALS AND METHODS: Twenty-one patients suffering from
      irregularly formed tracheostoma after laryngectomy followed by insertion of a
      speech valve were provided with a silicone tracheostomal prosthesis. They
      underwent subjective assessment of voice quality and breathing function according
      to a standardized general questionnaire and to the Voice Handicap Index (VHI).
      Furthermore, a clinical evaluation was performed including detection of
      peristomal leakage and phonation time. RESULTS AND DISCUSSION: Patients described
      a significant improvement of voice production with the tracheostomal prosthesis
      (averagely graded as 1.9 with and 3.2 without prosthesis, P = .0026). Breathing
      was also slightly improved by the prosthesis with an average grade of 1.7
      compared to 2.3 with a conventional cannula (P = .063). There was a strong
      correlation between self-evaluation and the total score of the VHI after
      insertion of the prosthesis (P < .0001). Minor local skin reactions caused by the
      adhesive were described by 5 of the 21 patients. CONCLUSIONS: A tracheostomal
      prosthesis represents an efficient alternative to surgical revision of
      irregularly formed tracheostoma after laryngectomy, enhancing voice production
      and breathing function.

PMID- 26307067
TI  - Calreticulin down-regulation inhibits the cell growth, invasion and cell cycle
      progression of human hepatocellular carcinoma cells.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most frequent cancers in
      the world. Calreticulin(CRT) is aberrantly overexpressed in many human cancer
      cells. The function of CRT in HCC cells remains unclear. We attempted to
      investigate the effects and the underlying mechanisms of CRT down-regulation on
      HCC cell growth, apoptosis, cell cycle progression and invasion. METHODS: To
      investigate the function of CRT in HCC cells, small interfering RNA (siRNA) was
      used to knock down the expression of CRT in SMMC7721 and HepG2 HCC cells. CRT
      expression was examined by Western blot and immunofluorescence. Cell
      proliferation was detected by CCK-8 assay. Cell cycle and apoptosis were measured
      by the flow cytometry. The invasion capability was assessed by transwell assay.
      The phosphorylation level of Akt was evaluated by Western blot. RESULTS: Compared
      with human hepatic cells L02, CRT was apparently up-regulated in SMMC7721, HepG2
      and Huh7 HCC cells. Down-regulation of CRT expression effectively inhibited HCC
      cell growth and invasion. CRT knockdown induced cell cycle arrest and the
      apoptosis in SMMC7721 and HepG2 cells. Furthermore, down-regulation of CRT
      expression significantly decreased the Akt phosphorylation. CONCLUSIONS: CRT was
      aberrantly over-expressed in HCC cell lines. CRT over-expression contributes
      greatly to HCC malignant behavior, likely via PI3K/Akt pathway. CRT could serve
      as a potential biomarker and therapeutic target for hepatocellular carcinoma.

PMID- 26307070
TI  - Positive Pressure Bronchoscopy Technique: Case Report.
AB  - OBJECTIVE: Foreign body aspiration into the tracheobronchial tree continues to be
      a challenging problem for otolaryngologists. This is especially true in patients
      with poor pulmonary reserve. METHODS: We describe a novel technique in which an
      endotracheal sheathed bronchoscope is used as a means to provide positive
      pressure ventilation simultaneously during foreign body extraction. RESULTS: This
      new technique afforded the bronchoscopist more time during retrieval of the
      foreign body where previous attempts were limited by rapid desaturations and the
      overall nature of the foreign body. CONCLUSION: The endotracheal sheathed
      bronchoscope is a safe and efficacious technique for challenging airway foreign
      bodies complicated by a patient's limited pulmonary reserve.

PMID- 26307071
TI  - Characterization of the Role of beta-Carotene 9,10-Dioxygenase in Macular Pigment
      Metabolism.
AB  - A family of enzymes collectively referred to as carotenoid cleavage oxygenases is
      responsible for oxidative conversion of carotenoids into apocarotenoids,
      including retinoids (vitamin A and its derivatives). A member of this family, the
      beta-carotene 9,10-dioxygenase (BCO2), converts xanthophylls to rosafluene and
      ionones. Animals deficient in BCO2 highlight the critical role of the enzyme in
      carotenoid clearance as accumulation of these compounds occur in tissues.
      Inactivation of the enzyme by a four-amino acid-long insertion has recently been
      proposed to underlie xanthophyll concentration in the macula of the primate
      retina. Here, we focused on comparing the properties of primate and murine BCO2s.
      We demonstrate that the enzymes display a conserved structural fold and
      subcellular localization. Low temperature expression and detergent choice
      significantly affected binding and turnover rates of the recombinant enzymes with
      various xanthophyll substrates, including the unique macula pigment meso
      zeaxanthin. Mice with genetically disrupted carotenoid cleavage oxygenases
      displayed adipose tissue rather than eye-specific accumulation of supplemented
      carotenoids. Studies in a human hepatic cell line revealed that BCO2 is expressed
      as an oxidative stress-induced gene. Our studies provide evidence that the
      enzymatic function of BCO2 is conserved in primates and link regulation of BCO2
      gene expression with oxidative stress that can be caused by excessive carotenoid
      supplementation.

PMID- 26307072
TI  - Choosing Subsamples for Sequencing Studies by Minimizing the Average Distance to
      the Closest Leaf.
AB  - Imputation of genotypes in a study sample can make use of sequenced or densely
      genotyped external reference panels consisting of individuals that are not from
      the study sample. It also can employ internal reference panels, incorporating a
      subset of individuals from the study sample itself. Internal panels offer an
      advantage over external panels because they can reduce imputation errors arising
      from genetic dissimilarity between a population of interest and a second,
      distinct population from which the external reference panel has been constructed.
      As the cost of next-generation sequencing decreases, internal reference panel
      selection is becoming increasingly feasible. However, it is not clear how best to
      select individuals to include in such panels. We introduce a new method for
      selecting an internal reference panel--minimizing the average distance to the
      closest leaf (ADCL)--and compare its performance relative to an earlier
      algorithm: maximizing phylogenetic diversity (PD). Employing both simulated data
      and sequences from the 1000 Genomes Project, we show that ADCL provides a
      significant improvement in imputation accuracy, especially for imputation of
      sites with low-frequency alleles. This improvement in imputation accuracy is
      robust to changes in reference panel size, marker density, and length of the
      imputation target region.

PMID- 26307073
TI  - Role of immunohistochemistry in the era of genetic testing in MYC-positive
      aggressive B-cell lymphomas: a study of 209 cases.
AB  - AIMS: MYC rearrangements with or without BCL2 rearrangements have been shown to
      be associated with poor prognosis and inferior survival in diffuse large B-cell
      lymphomas (DLBCL). Most of these cases are still diagnosed by fluorescent in situ
      hybridisation (FISH) testing, which is expensive, requires expertise and is not
      routinely available in all laboratories. Immunohistochemistry (IHC) is widely
      available and has the potential to be used as a screening test to identify cases
      with increased protein expression and select cases that require confirmatory
      testing. We correlated the expression of MYC and BCL2 by IHC with FISH studies in
      an attempt to define a cut-off value, which can be used by laboratories to select
      cases requiring confirmatory FISH testing. The prevalence of MYC-positive DLBCL
      and double-hit lymphoma (DHL) has also been studied. METHODS: 209 cases
      comprising of 15 cases of Burkitt lymphoma (BL), 13 cases of intermediate
      BL/DLBCL and 181 cases of DLBCL were included. IHC and FISH for MYC and BCL2 were
      performed and the results were correlated. RESULTS: The prevalence of MYC
      positive DLBCL and MYC/BCL2DHL was 13.4% and 7.4%, respectively, in our study.
      Germinal-centre subtype was more common in MYC-positive DLBCL and DHL. MYC
      positive DLBCL also showed higher median Ki-67 (>90%) and CD10 positivity as
      compared with MYC-negative cases. CONCLUSIONS: IHC can be used for screening
      cases, which require further confirmatory FISH testing. We recommend a cut-off
      value of >=30% for MYC by IHC; however, international standardisation of these
      values is necessary to provide uniformity among laboratories.

PMID- 26307074
TI  - Comparative evaluation of matrix-assisted laser desorption ionisation-time of
      flight mass spectrometry and conventional phenotypic-based methods for
      identification of clinically important yeasts in a UK-based medical microbiology
      laboratory.
AB  - AIMS: Performance of matrix-assisted laser desorption ionisation-time of flight
      mass spectrometry (MALDI-TOF MS) was compared in a side-by side-analysis with
      conventional phenotypic methods currently in use in our laboratory for
      identification of yeasts in a routine diagnostic setting. METHODS: A diverse
      collection of 200 clinically important yeasts (19 species, five genera) were
      identified by both methods using standard protocols. Discordant or unreliable
      identifications were resolved by sequencing of the internal transcribed spacer
      region of the rRNA gene. RESULTS: MALDI-TOF and conventional methods were in
      agreement for 182 isolates (91%) with correct identification to species level.
      Eighteen discordant results (9%) were due to rarely encountered species, hence
      the difficulty in their identification using traditional phenotypic methods.
      CONCLUSIONS: MALDI-TOF MS enabled rapid, reliable and accurate identification of
      clinically important yeasts in a routine diagnostic microbiology laboratory.
      Isolates with rare, unusual or low probability identifications should be
      confirmed using robust molecular methods.

PMID- 26307075
TI  - The lymphocyte-monocyte ratio in clinical practice.

PMID- 26307076
TI  - Loop-mediated isothermal amplification for rapid molecular detection of
      Enterocytozoon bieneusi in faecal specimens.
AB  - A loop-mediated isothermal amplification (LAMP) assay was developed to detect
      Enterocytozoon bieneusi DNA for the first time from human faecal specimens. Four
      primers specific for Enterocytozoon bieneusi were designed corresponding to small
      subunit rRNA gene sequences and tested on 100 human faecal specimens. Thirty-nine
      of the faecal specimens (39%) were confirmed positive for Enterocytozoon bieneusi
      by LAMP compared with 33% by PCR and 32% by light microscopy. LAMP yielded 94%
      sensitivity and 88% specificity compared with microscopy (sensitivity 48%,
      specificity 76%). No significant differences in positive detection of
      Enterocytozoon bieneusi were found among the three methods (P>0.05). However,
      LAMP has shown a substantial agreement with PCR (kappa = 0.78) and fair agreement
      was demonstrated between microscopy and PCR (kappa = 0.25). In conclusion, the
      LAMP assay proved to be useful as a simplified, rapid, sensitive and specific
      alternative molecular screening tool in the diagnosis of Enterocytozoon bieneusi
      in faecal specimens

PMID- 26307077
TI  - beta LACTA test for rapid detection of Enterobacteriaceae resistant to third
      generation cephalosporins from positive blood cultures using briefly incubated
      solid medium cultures.

PMID- 26307078
TI  - Genotypic diversity, pathogenic potential and the resistance profile of
      Salmonella Typhimurium strains isolated from humans and food from 1983 to 2013 in
      Brazil.
AB  - Salmonella enterica subsp. enterica serovar Typhimurium is one of the leading
      serovars that causes salmonellosis worldwide. However, few studies have
      molecularly characterized S. Typhimurium strains in Brazil. In this study, we
      genotyped 92 S. Typhimurium strains isolated from humans (43) and food (49)
      between 1983 and 2013 in Brazil using PFGE, multiple-locus variable number of
      tandem repeats analysis (MLVA) and enterobacterial repetitive intergenic
      consensus PCR (ERIC-PCR). Moreover, we assessed the frequency of 12 virulence
      markers by PCR and the resistance profile against 12 antimicrobials. More than
      85.8% of the strains studied carried 11 of the virulence markers or more. Thirty
      three strains (25%) were multidrug resistant (MDR). The 92 S. Typhimurium studied
      were grouped by PFGE as PFGE-A, PFGE-B1 and PFGE-B2; by MLVA as MLVA-A, MLVA-B1
      and MLVA-B2; and, finally, by ERIC-PCR as ERIC-A and ERIC-B. The strains isolated
      from humans before the mid-1990s were allocated to all clusters. The strains
      isolated from humans after the mid-1990s were distributed in the PFGE-B1, MLVA
      B1, MLVA-B2 and ERIC-A clusters. The strains isolated from food were distributed
      in all clusters, except in PFGE-B2. All typing results suggested that the S.
      Typhimurium strains of human clinical origin isolated before the mid-1990s were
      genetically more diverse, which might indicate the selection of a more adapted S.
      Typhimurium subtype after Salmonella Enteritidis became the most prevalent
      serovar in Brazil. Regarding strains isolated from food, the results suggest the
      current circulation of more than one subtype. Furthermore, the high frequency of
      virulence genes and the presence of MDR strains reinforces their potential hazard
      for humans and the risk of their presence in foods in Brazil.

PMID- 26307079
TI  - Influence of pH on bile sensitivity amongst various strains of Listeria
      monocytogenes under aerobic and anaerobic conditions.
AB  - Listeria monocytogenes is a dangerous bacterium that causes the food-borne
      disease listeriosis and accounts for nearly 20% of food-borne deaths. This
      organism can survive the body's natural defences within the digestive tract,
      including acidic conditions and bile. Although the bile response has been
      analysed, limited information is available concerning the ability of L.
      monocytogenes to resist bile under anaerobic conditions, especially at acidic pH,
      which mimics conditions within the duodenum. Additionally, it is not known how
      the bile response varies between serotypes. In this study, the survival of
      strains representing six serotypes was analysed under aerobic and anaerobic
      conditions following exposure to bile. Exposure to bile salts at acidic pH
      increased toxicity of bile, resulting in a significant reduction in survival for
      all strains tested. However, following this initial reduction, no significant
      reduction was observed for an additional 2 h except for strain 10403S (P =
      0.002). Anaerobic cultivation increased bile resistance, but a significant
      increase was only observed in virulent strains when exposed to bile at pH 5.5.
      Exposure to pH 3.0 prior to bile decreased viability amongst avirulent strains in
      bile in acidic conditions; oxygen availability did not influence viability.
      Together, the data suggested that being able to sense and respond to oxygen
      availability may influence the expression of stress response mechanisms, and this
      response may correspond to disease outcome. Further research is needed on
      additional strains to determine how L. monocytogenes senses and responds to
      oxygen and how this varies between invasive and non-invasive strains.

PMID- 26307080
TI  - Homozygous mutation in the eukaryotic translation initiation factor 2alpha
      phosphatase gene, PPP1R15B, is associated with severe microcephaly, short stature
      and intellectual disability.
AB  - Protein translation is an essential cellular process initiated by the association
      of a methionyl-tRNA with the translation initiation factor eIF2. The Met
      tRNA/eIF2 complex then associates with the small ribosomal subunit, other
      translation factors and mRNA, which together comprise the translational
      initiation complex. This process is regulated by the phosphorylation status of
      the alpha subunit of eIF2 (eIF2alpha); phosphorylated eIF2alpha attenuates
      protein translation. Here, we report a consanguineous family with severe
      microcephaly, short stature, hypoplastic brainstem and cord, delayed myelination
      and intellectual disability in two siblings. Whole-exome sequencing identified a
      homozygous missense mutation, c.1972G>A; p.Arg658Cys, in protein phosphatase 1,
      regulatory subunit 15b (PPP1R15B), a protein which functions with the PPP1C
      phosphatase to maintain dephosphorylated eIF2alpha in unstressed cells. The
      p.R658C PPP1R15B mutation is located within the PPP1C binding site. We show that
      patient cells have greatly diminished levels of PPP1R15B-PPP1C interaction, which
      results in increased eIF2alpha phosphorylation and resistance to cellular stress.
      Finally, we find that patient cells have elevated levels of PPP1R15B mRNA and
      protein, suggesting activation of a compensatory program aimed at restoring
      cellular homeostasis which is ineffective due to PPP1R15B alteration. PPP1R15B
      now joins the expanding list of translation-associated proteins which when
      mutated cause rare genetic diseases. 

PMID- 26307081
TI  - Distinct expression and function of whirlin isoforms in the inner ear and retina:
      an insight into pathogenesis of USH2D and DFNB31.
AB  - Usher syndrome (USH) is the most common inherited deaf-blindness with the
      majority of USH causative genes also involved in nonsyndromic recessive deafness
      (DFNB). The mechanism underlying this disease variation of USH genes is unclear.
      Here, we addressed this issue by investigating the DFNB31 gene, whose mutations
      cause USH2D or DFNB31 depending on their position. We found that the mouse DFNB31
      ortholog (Dfnb31) expressed different mRNA variants and whirlin protein isoforms
      in the cochlea and retina, where these isoforms played different roles spatially
      and temporally. Full-length (FL-) whirlin in photoreceptors and hair cell
      stereociliary bases is important for the USH type 2 protein complex, while FL-
      and C-terminal (C-) whirlins in hair cell stereociliary tips participate in
      stereociliary elongation. Mutations in the whirlin N-terminal region disrupted FL
      whirlin isoform in the inner ear and retina but not C-whirlin in the inner ear,
      and led to retinal degeneration as well as moderate to severe hearing loss. By
      contrast, a mutation in the whirlin C-terminal region eliminated all normal
      whirlin isoforms but generated a truncated N-terminal whirlin protein fragment,
      which was partially functional in the retina and thus prevented retinal
      degeneration. Mice with this mutation had profound hearing loss. In summary,
      disruption of distinct whirlin isoforms by Dfnb31 mutations leads to a variety of
      phenotype configurations and may explain the mechanism underlying the different
      disease manifestations of human DFNB31 mutations. Our findings have a potential
      to improve diagnosis and treatment of USH disease and quality of life in USH
      patients. 

PMID- 26307082
TI  - Transcriptional dysregulation of inflammatory/immune pathways after active
      vaccination against Huntington's disease.
AB  - Immunotherapy, both active and passive, is increasingly recognized as a powerful
      approach to a wide range of diseases, including Alzheimer's and Parkinson's.
      Huntington's disease (HD), an autosomal dominant disorder triggered by misfolding
      of huntingtin (HTT) protein with an expanded polyglutamine tract, could also
      benefit from this approach. Individuals can be identified genetically at the
      earliest stages of disease, and there may be particular benefits to a therapy
      that can target peripheral tissues in addition to brain. In this active
      vaccination study, we first examined safety and immunogenicity for a broad series
      of peptide, protein and DNA plasmid immunization protocols, using fragment
      (R6/1), and knock-in (zQ175) models. No safety issues were found. The strongest
      and most uniform immune response was to a combination of three non-overlapping
      HTT Exon1 coded peptides, conjugated to KLH, delivered with alum adjuvant. An
      N586-82Q plasmid, delivered via gene gun, also showed ELISA responses, mainly in
      the zQ175 strain, but with more variability, and less robust responses in HD
      compared with wild-type controls. Transcriptome profiling of spleens from the
      triple peptide-immunized cohort showed substantial HD-specific differences
      including differential activation of genes associated with innate immune
      responses, absence of negative feedback control of gene expression by regulators,
      a temporal dysregulation of innate immune responses and transcriptional
      repression of genes associated with memory T cell responses. These studies
      highlight critical issues for immunotherapy and HD disease management in general.

PMID- 26307084
TI  - Loss of lysyl oxidase-like 3 causes cleft palate and spinal deformity in mice.
AB  - In mammals, embryonic development are highly regulated morphogenetic processes
      that are tightly controlled by genetic elements. Failure of any one of these
      processes can result in embryonic malformation. The lysyl oxidase (LOX) family
      genes are closely related to human diseases. In this study, we investigated the
      essential role of lysyl oxidase-like 3 (LOXL3), a member of the LOX family, in
      embryonic development. Mice lacking LOXL3 exhibited perinatal lethality, and the
      deletion of the Loxl3 gene led to impaired development of the palate shelves,
      abnormalities in the cartilage primordia of the thoracic vertebrae and mild
      alveolar shrinkage. We found that the obvious decrease of collagen cross-links in
      palate and spine that was induced by the lack of LOXL3 resulted in cleft palate
      and spinal deformity. Thus, we provide critical in vivo evidence that LOXL3 is
      indispensable for mouse palatogenesis and vertebral column development. The Loxl3
      gene may be a candidate disease gene resulting in cleft palate and spinal
      deformity. 

PMID- 26307083
TI  - Muscle weakness in TPM3-myopathy is due to reduced Ca2+-sensitivity and impaired
      acto-myosin cross-bridge cycling in slow fibres.
AB  - Dominant mutations in TPM3, encoding alpha-tropomyosinslow, cause a congenital
      myopathy characterized by generalized muscle weakness. Here, we used a
      multidisciplinary approach to investigate the mechanism of muscle dysfunction in
      12 TPM3-myopathy patients. We confirm that slow myofibre hypotrophy is a
      diagnostic hallmark of TPM3-myopathy, and is commonly accompanied by skewing of
      fibre-type ratios (either slow or fast fibre predominance). Patient muscle
      contained normal ratios of the three tropomyosin isoforms and normal fibre-type
      expression of myosins and troponins. Using 2D-PAGE, we demonstrate that mutant
      alpha-tropomyosinslow was expressed, suggesting muscle dysfunction is due to a
      dominant-negative effect of mutant protein on muscle contraction. Molecular
      modelling suggested mutant alpha-tropomyosinslow likely impacts actin-tropomyosin
      interactions and, indeed, co-sedimentation assays showed reduced binding of
      mutant alpha-tropomyosinslow (R168C) to filamentous actin. Single fibre
      contractility studies of patient myofibres revealed marked slow myofibre specific
      abnormalities. At saturating [Ca(2+)] (pCa 4.5), patient slow fibres produced
      only 63% of the contractile force produced in control slow fibres and had reduced
      acto-myosin cross-bridge cycling kinetics. Importantly, due to reduced Ca(2+)
      sensitivity, at sub-saturating [Ca(2+)] (pCa 6, levels typically released during
      in vivo contraction) patient slow fibres produced only 26% of the force generated
      by control slow fibres. Thus, weakness in TPM3-myopathy patients can be directly
      attributed to reduced slow fibre force at physiological [Ca(2+)], and impaired
      acto-myosin cross-bridge cycling kinetics. Fast myofibres are spared; however,
      they appear to be unable to compensate for slow fibre dysfunction. Abnormal
      Ca(2+)-sensitivity in TPM3-myopathy patients suggests Ca(2+)-sensitizing drugs
      may represent a useful treatment for this condition. 

PMID- 26307086
TI  - Planned Home VBAC in the United States, 2004-2009: Outcomes, Maternity Care
      Practices, and Implications for Shared Decision Making.
AB  - BACKGROUND: In the United States, the number of planned home vaginal births after
      cesarean (VBACs) has increased. This study describes the maternal and neonatal
      outcomes for women who planned a VBAC at home with midwives who were contributing
      data to the Midwives Alliance of North America Statistics Project 2.0 cohort
      during the years 2004-2009. METHOD: Two subsamples were created from the parent
      cohort: 12,092 multiparous women without a prior cesarean and 1,052 women with a
      prior cesarean. Descriptive statistics were calculated for maternal and neonatal
      outcomes for both groups. Sensitivity analyses comparing women with a prior
      vaginal birth and those who were at the lowest risk with various subgroups in the
      parent cohort were also conducted. RESULTS: Women with a prior cesarean had a
      VBAC rate of 87 percent, although transfer rates were higher compared with women
      without a prior cesarean (18% vs 7%, p < 0.001). The most common indication for
      transfer was failure to progress. Women with a prior cesarean had higher
      proportions of blood loss, maternal postpartum infections, uterine rupture, and
      neonatal intensive care unit admissions than those without a prior cesarean. Five
      neonatal deaths (4.75/1,000) occurred in the prior cesarean group compared with
      1.24/1,000 in multiparas without a history of cesarean (p = 0.015). CONCLUSION:
      Although there is a high likelihood of a vaginal birth at home, women planning a
      home VBAC should be counseled regarding maternal transfer rates and potential for
      increased risk to the newborn, particularly if uterine rupture occurs in the home
      setting.

PMID- 26307085
TI  - High-dose folic acid supplementation alters the human sperm methylome and is
      influenced by the MTHFR C677T polymorphism.
AB  - Dietary folate is a major source of methyl groups required for DNA methylation,
      an epigenetic modification that is actively maintained and remodeled during
      spermatogenesis. While high-dose folic acid supplementation (up to 10 times the
      daily recommended dose) has been shown to improve sperm parameters in infertile
      men, the effects of supplementation on the sperm epigenome are unknown. To assess
      the impact of 6 months of high-dose folic acid supplementation on the sperm
      epigenome, we studied 30 men with idiopathic infertility. Blood folate
      concentrations increased significantly after supplementation with no significant
      improvements in sperm parameters. Methylation levels of the differentially
      methylated regions of several imprinted loci (H19, DLK1/GTL2, MEST, SNRPN,
      PLAGL1, KCNQ1OT1) were normal both before and after supplementation. Reduced
      representation bisulfite sequencing (RRBS) revealed a significant global loss of
      methylation across different regions of the sperm genome. The most marked loss of
      DNA methylation was found in sperm from patients homozygous for the
      methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, a common
      polymorphism in a key enzyme required for folate metabolism. RRBS analysis also
      showed that most of the differentially methylated tiles were located in DNA
      repeats, low CpG-density and intergenic regions. Ingenuity Pathway Analysis
      revealed that methylation of promoter regions was altered in several genes
      involved in cancer and neurobehavioral disorders including CBFA2T3, PTPN6,
      COL18A1, ALDH2, UBE4B, ERBB2, GABRB3, CNTNAP4 and NIPA1. Our data reveal
      alterations of the human sperm epigenome associated with high-dose folic acid
      supplementation, effects that were exacerbated by a common polymorphism in MTHFR.

PMID- 26307088
TI  - DNMT1-associated long non-coding RNAs regulate global gene expression and DNA
      methylation in colon cancer.
AB  - The cancer epigenome exhibits global loss of DNA methylation, which contributes
      to genomic instability and aberrant gene expression by mechanisms that are yet to
      be fully elucidated. We previously discovered over 3300 long non-coding (lnc)RNAs
      in human cells and demonstrated that specific lncRNAs regulate gene expression
      via interactions with chromatin-modifying complexes. Here, we tested whether
      lncRNAs could also associate with DNA methyltransferases to regulate DNA
      methylation and gene expression. Using RIP-seq, we identified a subset of lncRNAs
      that interact with the DNA methyltransferase DNMT1 in a colon cancer cell line,
      HCT116. One lncRNA, TCONS_00023265, which we named DACOR1 (DNMT1-associated Colon
      Cancer Repressed lncRNA 1), shows high, tissue-specific expression in the normal
      colon (including colon crypts) but was repressed in a panel of colon tumors and
      patient-derived colon cancer cell lines. We identified the genomic occupancy
      sites of DACOR1, which we found to significantly overlap with known
      differentially methylated regions (DMRs) in colon tumors. Induction of DACOR1 in
      colon cancer cell lines significantly reduced their ability to form colonies in
      vitro, suggesting a growth suppressor function. Consistent with the observed
      phenotype, induction of DACOR1 led to the activation of tumor-suppressor pathways
      and attenuation of cancer-associated metabolic pathways. Notably, DACOR1
      induction resulted in down-regulation of Cystathionine beta-synthase, which is
      known to lead to increased levels of S-adenosyl methionine-the key methyl donor
      for DNA methylation. Collectively, our results demonstrate that deregulation of
      DNMT1-associated lncRNAs contributes to aberrant DNA methylation and gene
      expression during colon tumorigenesis. 

PMID- 26307089
TI  - Several Conventional Risk Markers Suggesting Presence of Albuminuria Are Weak
      Among Rural Africans With Hypertension.
AB  - The objective of this cross-sectional study was to investigate risk markers
      indicating the presence of albuminuria in patients with hypertension in rural sub
      Saharan Africa (SSA). Urine albumin-creatinine ratio, glycated hemoglobin (HbA1c
      ), blood pressure, anthropometry, and other patient characteristics including
      medications were assessed. We identified 160 patients with hypertension, of whom
      68 (42.5%) were co-diagnosed with diabetes mellitus (DM). Among the included
      participants, 57 (35.6%) had albuminuria (microalbuminuria [n=43] and
      macroalbuminuria [n=14]). A backward multivariate logistic regression model
      identified age (per 10-year increment) (odds ratio [OR], 1.42; 95% confidence
      interval [CI], 1.03-1.95), HbA1c >53 compared with <48 mmol/mol (OR, 3.81; 95%
      CI, 1.74-8.35), and treatment with dihydropyridine calcium channel blockers (OR,
      2.59; 95% CI, 1.09-6.16) as the variables significantly associated with
      albuminuria. Only dysregulated DM and age were the conventional risk markers that
      seemed to suggest albuminuria among patients with hypertension in rural SSA.

PMID- 26307090
TI  - In silico and in vitro methods to optimize the performance of experimental
      gastroretentive floating mini-tablets.
AB  - CONTEXT: Development of floating drug delivery systems (FDDS) is challenging. To
      facilitate this task, an evaluation method was proposed, which allows for a
      combined investigation of drug release and flotation. OBJECTIVE: It was the aim
      of the study to use functionalized calcium carbonate (FCC)-based lipophilic mini
      tablet formulations as a model system to design FDDS with a floating behavior
      characterized by no floating lag time, prolonged flotation and loss of floating
      capability after complete drug release. MATERIALS AND METHODS: Release of the
      model drug caffeine from the mini-tablets was assessed in vitro by a custom-built
      stomach model. A cellular automata-based model was used to simulate tablet
      dissolution. Based on the in silico data, floating forces were calculated and
      analyzed as a function of caffeine release. RESULTS AND DISCUSSION: Two floating
      behaviors were identified for mini-tablets: linear decrease of the floating force
      and maintaining of the floating capability until complete caffeine release. An
      optimal mini-tablet formulation with desired drug release time and floating
      behavior was developed and tested. CONCLUSION: A classification system for a
      range of varied floating behavior of FDDS was proposed. The FCC-based mini
      tablets had an ideal floating behavior: duration of flotation is defined and
      floating capability decreases after completion of drug release.

PMID- 26307087
TI  - Genetic variants and cellular stressors associated with exfoliation syndrome
      modulate promoter activity of a lncRNA within the LOXL1 locus.
AB  - Exfoliation syndrome (XFS) is a common, age-related, systemic fibrillinopathy. It
      greatly increases risk of exfoliation glaucoma (XFG), a major worldwide cause of
      irreversible blindness. Coding variants in the lysyl oxidase-like 1 (LOXL1) gene
      are strongly associated with XFS in all studied populations, but a functional
      role for these variants has not been established. To identify additional
      candidate functional variants, we sequenced the entire LOXL1 genomic locus (~40
      kb) in 50 indigenous, black South African XFS cases and 50 matched controls. The
      variants with the strongest evidence of association were located in a well
      defined 7-kb region bounded by the 3'-end of exon 1 and the adjacent region of
      intron 1 of LOXL1. We replicated this finding in US Caucasian (91 cases/1031
      controls), German (771 cases/1365 controls) and Japanese (1484 cases/1188
      controls) populations. The region of peak association lies upstream of LOXL1-AS1,
      a long non-coding RNA (lncRNA) encoded on the opposite strand of LOXL1. We show
      that this region contains a promoter and, importantly, that the strongly
      associated XFS risk alleles in the South African population are functional
      variants that significantly modulate the activity of this promoter. LOXL1-AS1
      expression is also significantly altered in response to oxidative stress in human
      lens epithelial cells and in response to cyclic mechanical stress in human
      Schlemm's canal endothelial cells. Taken together, these findings support a
      functional role for the LOXL1-AS1 lncRNA in cellular stress response and suggest
      that dysregulation of its expression by genetic risk variants plays a key role in
      XFS pathogenesis. 

PMID- 26307091
TI  - Live birth rates after modified natural cycle compared with high-dose FSH
      stimulation using GnRH antagonists in poor responders.
AB  - STUDY QUESTION: Do live birth rates differ between modified natural cycles (MNCs)
      and cycles using high-dose follicle stimulating hormone (HDFSH) with
      gonadotrophin-releasing hormone (GnRH) antagonist in poor responder patients?
      SUMMARY ANSWER: Live birth rates are significantly higher in MNC compared with
      HDFSH GnRH antagonist cycles in poor responder patients. WHAT IS KNOWN ALREADY:
      Previous data on the efficiency of MNC in poor responders are very limited and
      suggest that MNC in vitro fertilization (IVF) does not offer a realistic solution
      for parenthood in these patients, since live birth rates are disappointingly low.
      To date, no studies exist comparing MNC with HDFSH stimulation protocols in poor
      responders. STUDY DESIGN, SIZE, DURATION: The present retrospective study
      included 161 MNCs (106 women in the MNC group) and 164 HDFSH antagonist cycles
      (136 women in the HDFSH group) performed between January 2008 and December 2013
      at Eugonia Assisted Reproduction Unit. The patients included in the study had to
      fulfill the Bologna criteria for the definition of poor ovarian response.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Irrespective of their age, poor
      responder patients should have a diminished ovarian reserve as shown by low
      antral follicle count (<=5) and increased basal FSH (>12 IU/l), and one or more
      previous failed IVF cycles in which <=3 oocytes were retrieved using a high
      gonadotrophin dose. Analysis was performed by adjusting for the non-independence
      of the data. MAIN RESULTS AND THE ROLE OF CHANCE: The probability of live birth
      was significantly higher in the MNC when compared with the HDFSH group (OR: 4.01,
      95% CI: 1.14-14.09), after adjusting for basal FSH, female age and cause of
      infertility, variables which were shown to be associated with the probability of
      live birth in univariable analysis. MNCs were characterized by significantly
      lower total gonadotrophin dose (490.0 +/- 35.2 IU versus 2826.1 +/- 93.4 IU, P <
      0.001), lower estradiol concentrations (237.5 +/- 12.3 pg/ml versus 487.3 +/-
      29.8 pg/ml, P < 0.001), fewer follicles present on the day of hCG (1.9 +/- 0.1
      versus 3.2 +/- 0.2, P < 0.001), fewer oocytes retrieved (1.1 +/- 0.01 versus 2.4
      +/- 0.1, P < 0.001), fewer oocytes fertilized (0.7 +/- 0.1 versus 1.4 +/- 0.1, P
      < 0.001), fewer embryos transferred (0.7 +/- 0.1 versus 1.4 +/- 0.1, P < 0.001),
      fewer good-quality embryos available (0.5 +/- 0.1 versus 0.8 +/- 0.1, P < 0.001)
      and fewer good-quality embryos transferred (0.5 +/- 0.05 versus 0.8 +/- 0.1, P <
      0.001) compared with the HDFSH group. However, the proportion of cycles with at
      least one good-quality embryo transferred per started cycle was similar between
      the two groups compared (62.5, 95% CI: 52.7-72.3 versus 62.7, 95% CI: 53.0-72.5,
      respectively). LIMITATIONS, REASONS FOR CAUTION: This is a retrospective
      comparison between MNC and HDFSH GnRH antagonist protocols in a large group of
      poor responder patients according to the Bologna criteria. Although the two
      groups compared were not imbalanced for all basic characteristics and
      multivariate analysis were performed to adjust for all known confounders, it
      cannot be excluded that non-apparent sources of bias might still be present.
      Future randomized controlled trials are necessary to verify the present findings.
      WIDER IMPLICATIONS OF THE FINDINGS: Both MNC and HDFSH antagonist protocols offer
      very low chances of live birth in poor responder patients who fulfill the Bologna
      criteria. However, MNC-IVF is a more patient-friendly approach, with a higher
      probability of live birth compared with the HDFSH antagonist protocol. In this
      respect, the current data might be of help in counseling such patients, who do
      not wish to undergo oocyte donation, prior to abandoning treatment altogether
      and/or proceeding to adoption. STUDY FUNDING/COMPETING INTERESTS: No funding was
      obtained. C.A.V. reports personal fees and non-financial support from Merck,
      Sharp and Dome, personal fees and non-financial support from Merck Serono,
      personal fees and non-financial support from IPSEN Hellas S.A. outside the
      submitted work. B.C.T. reports grants from Merck Serono, grants from Merck Sharp
      & Dohme, personal fees from IBSA, personal fees from Merck Sharp & Dohme and
      personal fees from Ovascience outside the submitted work .

PMID- 26307092
TI  - Soluble human leukocyte antigen G5 polarizes differentiation of macrophages
      toward a decidual macrophage-like phenotype.
AB  - STUDY QUESTION: What are the actions of soluble human leukocyte antigen G5
      (sHLAG5) on macrophage differentiation? SUMMARY ANSWER: sHLAG5 polarizes the
      differentiation of macrophages toward a decidual macrophage-like phenotype, which
      could regulate fetomaternal tolerance and placental development. WHAT IS KNOWN
      ALREADY: sHLAG5 is a full-length soluble isoform of human leukocyte antigen
      implicated in immune tolerance during pregnancy. Low or undetectable circulating
      level of sHLAG5 in first trimester of pregnancy is associated with pregnancy
      complications such as pre-eclampsia and spontaneous abortion. Decidual
      macrophages are located in close proximity to invasive trophoblasts, and are
      involved in regulating fetomaternal tolerance and placental development. STUDY
      DESIGN, SIZE, DURATION: Human peripheral blood monocytes were differentiated into
      macrophages by treatment with granulocyte macrophage colony-stimulating factor in
      the presence or absence of recombinant sHLAG5 during the differentiation process.
      The phenotypes and the biological activities of the resulting macrophages were
      compared. PARTICIPANTS/MATERIALS, SETTING, METHODS: Recombinant sHLAG5 was
      produced in Escherichia coli BL21 and the protein identity was verified by tandem
      mass spectrometry. The expression of macrophage markers were analyzed by flow
      cytometry and quantitative PCR. Phagocytosis was determined by flow cytometry.
      Indoleamine 2,3-dioxygenase 1 expression and activity were measured by western
      blot analysis and kynurenine assay, respectively. Cell proliferation and cell
      cycling were determined by fluorometric cell proliferation assay and flow
      cytometry, respectively. Cytokine secretion was determined by cytokine array and
      ELISA kits. Intracellular cytokine expression was measured by flow cytometry.
      Cell invasion and migration were determined by trans-well invasion and migration
      assay, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: sHLAG5 drove the
      differentiation of macrophages with 'immuno-modulatory' characteristics,
      including reduced expression of M1 macrophage marker CD86 and increased
      expression of M2 macrophage marker CD163. sHLAG5-polarized macrophages showed
      enhanced phagocytic activity. They also had higher expression and activity of
      indoleamine 2,3-dioxygenase 1, a phenotypic marker of decidual macrophages, which
      inhibited proliferation of autologous T-cells via induction of G0/G1 cell cycle
      arrest. In addition, sHLAG5-polarized macrophages had an increased secretion of
      interleukin-6 and C-X-C motif ligand 1, which inhibited interferon-gamma
      production in T-cells and induction of trophoblast invasion, respectively.
      LIMITATIONS, REASONS FOR CAUTION: Most information on the phenotypes and
      biological activities of human decidual macrophages are based on past
      literatures. A direct comparison between sHLAG5-polarized macrophages and primary
      decidual macrophages is required to verify the present observations. WIDER
      IMPLICATIONS OF THE FINDINGS: This is the first study on the role of sHLAG5 in
      macrophage differentiation. Further study on the mechanism that regulates the
      differentiation process of macrophages would enhance our understanding on the
      physiology of early pregnancy. STUDY FUNDING/COMPETING INTERESTS: This work was
      supported in part by the Hong Kong Research Grant Council Grant HKU774212 and the
      University of Hong Kong Grant 201309176126. The authors have no competing
      interests to declare. TRIAL REGISTRATION NUMBER: Nil.

PMID- 26307093
TI  - Peritoneal fluid modifies the microRNA expression profile in endometrial and
      endometriotic cells from women with endometriosis.
AB  - STUDY QUESTION: Could peritoneal fluid (PF) from patients with endometriosis
      alter the microRNA (miRNA) expression profile in endometrial and endometriotic
      cells from patients? SUMMARY ANSWER: PF from patients with endometriosis modifies
      the miRNA expression profile in endometrial cells from patients. WHAT IS KNOWN
      ALREADY: Angiogenesis is a pivotal system in the development of endometriosis,
      and dysregulated miRNA expression in this disease has been reported. However, to
      our knowledge, the effect of PF from patients on the miRNA expression profile of
      patient endometrial cells has not been reported. Moreover, an effect of three
      miRNAs (miR-16-5p, miR-29c-3p and miR-424-5p) on the regulation of vascular
      endothelial growth factor (VEGF)-A mRNA translation in endometrial cells from
      patients with endometriosis has not been demonstrated. STUDY DESIGN, SIZE,
      DURATION: Primary cultures of stromal cells from endometrium from 8 control women
      (control cells) and 11 patients with endometriosis (eutopic cells) and ovarian
      endometriomas (ectopic cells) were treated with PF from control women (CPF) and
      patients (EPF) or not treated (0PF) in order to evaluate the effect of PF on
      miRNA expression in these cells. PARTICIPANTS/MATERIALS, SETTING, METHODS: MiRNA
      expression arrays (Affymetrix platform) were prepared from cells (control,
      eutopic, ectopic) treated with CPF, EPF or 0PF. Results from arrays were
      validated by quantitative reverse transcription-polymerase chain reaction in
      cultures from 8 control endometrium, 11 eutopic endometrium and 11 ovarian
      endometriomas. Functional experiments were performed in primary cell cultures
      using mimics for miRNAs miR-16-5p, miR-29c-3p and miR-424-5p to assess their
      effect as VEGF-A expression regulators. To confirm a repressive action of miR-29c
      3p through forming miRNA:VEGFA duplexes, we performed luciferase expression
      assays. MAIN RESULTS AND THE ROLE OF CHANCE: EPF modified the miRNA expression
      profile in eutopic cells. A total of 267 miRNAs were modified in response to EPF
      compared with 0PF in eutopic cells. Nine miRNAs (miR-16-5p, miR-21-5p, miR-29c
      3p, miR-106b-5p, miR-130a-5p, miR-149-5p, miR-185-5p, miR-195-5p, miR-424-5p)
      that were differently expressed in response to EPF, and which were potential
      targets involved in angiogenesis, proteolysis or endometriosis, were validated in
      further experiments (control = 8, eutopic = 11, ectopic = 11). Except for miR-149
      5p, all validated miRNAs showed significantly lower levels (miR-16-5p, miR-106b
      5p, miR-130a-5p; miR-195-5p and miR-424-5p, P < 0.05; miR-21-5p, miR-29c-3p and
      miR-185-5p, P < 0.01) after EPF treatment in primary cell cultures from eutopic
      endometrium from patients in comparison with 0PF. Transfection of stromal cells
      with mimics of miRNAs miR-16-5p, miR-29c-3p and miR-424-5p showed a significant
      down-regulation of VEGF-A protein expression. However, VEGFA mRNA expression
      after mimic transfection was not significantly modified, indicating the miRNAs
      inhibited VEGF-A mRNA translation rather than degrading VEGFA mRNA. Luciferase
      experiments also corroborated VEGF-A as a target gene of miR-29c-3p. LIMITATIONS,
      REASONS FOR CAUTION: The study was performed in an in vitro model of
      endometriosis using stromal cells. This model is just a representation to try to
      elucidate the molecular mechanisms involved in the development of endometriosis.
      Further studies to identify the pathways involved in this miRNA expression
      modification in response to PF from patients are needed. WIDER IMPLICATIONS OF
      THE FINDINGS: This is the first study describing a modified miRNA expression
      profile in eutopic cells from patients in response to PF from patients. These
      promising results improve the body of knowledge on endometriosis pathogenesis and
      could open up new therapeutic strategies for the treatment of endometriosis
      through the use of miRNAs. STUDY FUNDING/COMPETING INTERESTS: This work was
      supported by research grants by ISCIII and FEDER (PI11/00091, PI11/00566,
      PI14/01309, PI14/00253 and FI12/00012), RIC (RD12/0042/0029 and RD12/0042/0050),
      IIS La Fe 2011-211, Prometeo 2011/027 and Contrato Sara Borrell CD13/0005. There
      are no conflicts of interest to declare.

PMID- 26307094
TI  - High-resolution mass spectrometry glycoprofiling of intact transferrin for
      diagnosis and subtype identification in the congenital disorders of
      glycosylation.
AB  - Diagnostic screening of the congenital disorders of glycosylation (CDG) generally
      involves isoelectric focusing of plasma transferrin, a robust method easily
      integrated in medical laboratories. Structural information is needed as the next
      step, as required for the challenging classification of Golgi glycosylation
      defects (CDG-II). Here, we present the use of high-resolution nano liquid
      chromatography-chip (C8)-quadrupole time of flight mass spectrometry (nanoLC-chip
      [C8]-QTOF MS) for protein-specific glycoprofiling of intact transferrin, which
      allows screening and direct diagnosis of a number of CDG-II defects. Transferrin
      was immunopurified from 10 MUL of plasma and analyzed by nanoLC-chip-QTOF MS.
      Charge distribution raw data were deconvoluted by Mass Hunter software to
      reconstructed mass spectra. Plasma samples were processed from controls (n = 56),
      patients with known defects (n = 30), and patients with secondary (n = 6) or
      unsolved (n = 3) cause of abnormal glycosylation. This fast and robust method,
      established for CDG diagnostics, requires only 2 hours analysis time, including
      sample preparation and analysis. For CDG-I patients, the characteristic loss of
      complete N-glycans could be detected with high sensitivity. Known CDG-II defects
      (phosphoglucomutase 1 [PGM1-CDG], mannosyl (alpha-1,6-)-glycoprotein beta-1,2-N
      acetylglucosaminyltransferase [MGAT2-CDG], beta-1,4-galactosyltransferase 1
      [B4GALT1-CDG], CMP-sialic acid transporter [SLC35A1-CDG], UDP-galactose
      transporter [SLC35A2-CDG] and mannosyl-oligosaccharide 1,2-alpha-mannosidase
      [MAN1B1-CDG]) resulted in characteristic diagnostic profiles. Moreover, in the
      group of Golgi trafficking defects and unsolved CDG-II patients, distinct
      profiles were observed, which facilitate identification of the specific CDG
      subtype. The established QTOF method affords high sensitivity and resolution for
      the detection of complete glycan loss and structural assignment of truncated
      glycans in a single assay. The speed and robustness allow its clinical diagnostic
      application as a first step in the diagnostic procedure for CDG defects.

PMID- 26307096
TI  - Conservation Physiology and Conservation Pathogens: White-Nose Syndrome and
      Integrative Biology for Host-Pathogen Systems.
AB  - Conservation physiology aims to apply an understanding of physiological
      mechanisms to management of imperiled species, populations, or ecosystems. One
      challenge for physiologists hoping to apply their expertise to conservation is
      connecting the mechanisms we study, often in the laboratory, with the vital rates
      of populations in the wild. There is growing appreciation that infectious
      pathogens can threaten populations and species, and represent an important issue
      for conservation. Conservation physiology has much to offer in terms of
      addressing the threat posed to some host species by infectious pathogens. At the
      same time, the well-developed theoretical framework of disease ecology could
      provide a model to help advance the application of physiology to a range of other
      conservation issues. Here, I use white-nose syndrome (WNS) in hibernating North
      American bats as an example of a conservation problem for which integrative
      physiological research has been a critical part of research and management. The
      response to WNS highlights the importance of a well-developed theoretical
      framework for the application of conservation physiology to a particular threat.
      I review what is known about physiological mechanisms associated with mortality
      from WNS and emphasize the value of combining a strong theoretical background
      with integrative physiological studies in order to connect physiological
      mechanisms with population processes and thereby maximize the potential benefits
      of conservation physiology. 

PMID- 26307095
TI  - The Escherichia coli NarL receiver domain regulates transcription through
      promoter specific functions.
AB  - BACKGROUND: The Escherichia coli response regulator NarL controls transcription
      of genes involved in nitrate respiration during anaerobiosis. NarL consists of
      two domains joined by a linker that wraps around the interdomain interface.
      Phosphorylation of the NarL N-terminal receiver domain (RD) releases the,
      otherwise sequestered, C-terminal output domain (OD) that subsequently binds
      specific DNA promoter sites to repress or activate gene expression. The aim of
      this study is to investigate the extent to which the NarL OD and RD function
      independently to regulate transcription, and the affect of the linker on OD
      function. RESULTS: NarL OD constructs containing different linker segments were
      examined for their ability to repress frdA-lacZ or activate narG-lacZ reporter
      fusion genes. These in vivo expression assays revealed that the NarL OD, in the
      absence or presence of linker helix alpha6, constitutively repressed frdA-lacZ
      expression regardless of nitrate availability. However, the presence of the
      linker loop alpha5-alpha6 reversed this repression and also showed impaired DNA
      binding in vitro. The OD alone could not activate narG-lacZ expression; this
      activity required the presence of the NarL RD. A footprint assay demonstrated
      that the NarL OD only partially bound recognition sites at the narG promoter, and
      the binding affinity was increased by the presence of the phosphorylated RD.
      Analytical ultracentrifugation used to examine domain oligomerization showed that
      the NarL RD forms dimers in solution while the OD is monomeric. CONCLUSIONS: The
      NarL RD operates as an on-off switch to occlude or release the OD in a nitrate
      responsive manner, but has additional roles to directly stimulate transcription
      at promoters for which the OD lacks independent function. One such role of the RD
      is to enhance the DNA binding affinity of the OD to target promoter sites. The
      data also imply that NarL phosphorylation results in RD dimerization and in the
      separation of the entire linker region from the OD.

PMID- 26307097
TI  - Diagnosis and therapy of antiphospholipid syndrome.
AB  - Antiphospholipid syndrome (APS) is a clinical condition that has not been well
      defined yet. Although the clinical component is well established, the laboratory
      part is a mood issue. According to current guidelines, 3 tests (lupus
      anticoagulant, anticardiolipin, and anti beta2-glycoprotein I antibodies) are
      officially recommended to assess the presence of antiphospholipid antibodies.
      According to test positivity, patients are classified into categories in clinical
      studies. However, it is now clear that classification categories have a different
      impact on the clinical course of APS. Indeed, patients and healthy carriers with
      a full positive antibody profile (triple positivity) are those at the highest
      risk of events. Patients with a single test positivity are those at a lower risk.
      In this review, on the basis of a laboratory profile, we grade the diagnosis of
      APS into definite, probable/possible, and uncertain. We also discuss secondary
      prevention of thrombotic APS, prevention of pregnancy morbidity, and treatment of
      catastrophic APS. Finally, new tools in laboratory diagnosis and treatment are
      highlighted. 

PMID- 26307098
TI  - Relationship Quality in Non-Cognitively Impaired Mother-Daughter Care Dyads: A
      Systematic Review.
AB  - More than 60 million Americans provide care to a family member; roughly two
      thirds are women providing care to aging mothers. Despite the protective nature
      of relationship quality, little attention has been given to its role in mother
      daughter care dyads, particularly in mothers without cognitive impairment. A
      systematic appraisal of peer-reviewed, English language research was conducted.
      Nineteen articles met criteria. When relationship quality is positive, mother
      daughter dyads enjoy rewards and mutuality, even when conflict occurs. Daughters
      grow more emotionally committed to mothers' over the care trajectory, despite
      increasing demands. Daughters' commitment deepens as mothers physically decline,
      and mothers remain engaged, emotional partners. When relationship quality is
      ambivalent or negative, burden, conflict, and blame conspire, creating a
      destructive cycle. Avenues for continuing study, including utilizing the dyad as
      the unit of analysis, troubled dyads, longitudinal assessment, and end of life
      context, are needed before interventions to improve mother-daughter relationship
      quality may be successfully implemented. 

PMID- 26307099
TI  - A "universal" model of metastatic cancer, its parametric forms and their
      identification: what can be learned from site-specific volumes of metastases.
AB  - We develop a methodology for estimating unobservable characteristics of the
      individual natural history of metastatic cancer from the volume of the primary
      tumor and site-specific volumes of metastases measured before, or shortly after,
      the start of treatment. In particular, we address the question as to what
      information about natural history of cancer can and cannot be gained from this
      type of data. Estimation of the natural history of cancer is based on
      parameterization of a very general mathematical model of cancer progression
      accounting for primary tumor growth, shedding of metastases, their selection,
      latency and growth in a given secondary site. This parameterization assumes
      Gompertz (and, as a limiting case, exponential) growth of the primary tumor,
      exponential growth of metastases, and exponential distribution of metastasis
      latency times. We find identifiable parameters of this model and give a rigorous
      proof of their identifiability. As an illustration, we analyze a clinical case of
      renal cancer patient who developed 55 lung metastases whose volumes were measured
      through laborious reading of CT images. The model with maximum likelihood
      parameters provided an excellent fit to this data. We uncovered many aspects of
      this patient's cancer natural history and showed that, according to the model,
      onset of metastasis occurred long before primary tumor became clinically
      detectable. 

PMID- 26307100
TI  - Suppression of different classes of somatic mutations in Arabidopsis by vir gene
      expressing Agrobacterium strains.
AB  - BACKGROUND: Agrobacterium infection, which is widely used to generate transgenic
      plants, is often accompanied by T-DNA-linked mutations and transpositions in
      flowering plants. It is not known if Agrobacterium infection also affects the
      rates of point mutations, somatic homologous recombinations (SHR) and frame-shift
      mutations (FSM). We examined the effects of Agrobacterium infection on five types
      of somatic mutations using a set of mutation detector lines of Arabidopsis
      thaliana. To verify the effect of secreted factors, we exposed the plants to
      different Agrobacterium strains, including wild type (Ach5), its derivatives
      lacking vir genes, oncogenes or T-DNA, and the heat-killed form for 48 h post
      infection; also, for a smaller set of strains, we examined the rates of three
      types of mutations at multiple time-points. The mutation detector lines carried a
      non-functional beta-glucuronidase gene (GUS) and a reversion of mutated GUS to
      its functional form resulted in blue spots. Based on the number of blue spots
      visible in plants grown for a further two weeks, we estimated the mutation
      frequencies. RESULTS: For plants co-cultivated for 48 h with Agrobacterium, if
      the strain contained vir genes, then the rates of transversions, SHRs and FSMs
      (measured 2 weeks later) were lower than those of uninfected controls. In
      contrast, co-cultivation for 48 h with any of the Agrobacterium strains raised
      the transposition rates above control levels. The multiple time-point study
      showed that in seedlings co-cultivated with wild type Ach5, the reduced rates of
      transversions and SHRs after 48 h co-cultivation represent an apparent
      suppression of an earlier short-lived increase in mutation rates (peaking for
      plants co-cultivated for 3 h). An increase after 3 h co-cultivation was also seen
      for rates of transversions (but not SHR) in seedlings exposed to the strain
      lacking vir genes, oncogenes and T-DNA. However, the mutation rates in plants co
      cultivated for longer times with this strain subsequently dropped below levels
      seen in uninfected controls, consistent with the results of the single time-point
      study. CONCLUSIONS: The rates of various classes of mutations that result from
      Agrobacterium infection depend upon the duration of infection and the type of
      pathogen derived factors (such as Vir proteins, oncoproteins or T-DNA) possessed
      by the strain. Strains with vir genes, including the type used for plant
      transformation, suppressed selected classes of somatic mutations. Our study also
      provides evidence of a pathogen that can at least partly counter the induction of
      mutations in an infected plant.

PMID- 26307101
TI  - Axillary lymph nodes metastasis in a patient with recurrent papillary thyroid
      cancer: a case report.
AB  - INTRODUCTION: Thyroid cancer is the most common endocrine malignancy; the most
      common type of thyroid cancer is papillary thyroid cancer which accounts for
      approximately 90% of all thyroid cancers. Previously defined prognostic factors
      of papillary thyroid cancer include age, gender, tumor size, extrathyroidal
      extension, and distant metastasis. Cervical lymph node metastases are very common
      in patients with papillary thyroid cancer. Although papillary thyroid cancer has
      an excellent prognosis, lymphatic spread is associated with an increased risk of
      locoregional recurrence. Axillary metastasis is not a common finding in the
      classic type of papillary carcinoma; hence, a limited number of case reports have
      described the exceptional and rare metastatic spread of papillary thyroid
      carcinomas to the axilla. CASE PRESENTATION: We report a case of metastatic
      axillary lymphadenopathy in a 61-year-old Egyptian man with a recurrent papillary
      thyroid cancer. He had a history of total thyroidectomy with right radical neck
      dissection 18 months ago. He presented to our cancer clinic at the Oncology
      Centre -Mansoura University with recurrent mass at the right lower parotid
      region, left cervical lymphadenopathy and left axillary lymphadenopathy. Removal
      of the recurrent right intraparotid mass, left comprehensive neck dissection and
      left axillary dissection were performed and the postoperative pathology report
      showed infiltration of the cervical and axillary lymph nodes by metastatic
      papillary thyroid cancer. CONCLUSIONS: Axillary lymph node enlargement in a
      patient with papillary thyroid cancer should be considered metastatic from
      thyroid until proved otherwise. Careful thorough examination of patients with
      recurrent thyroid cancer is essential to address any unusual metastasis.

PMID- 26307102
TI  - They can't bury you while you're still moving: A review of the European
      Respiratory Society statement on physical activity in chronic obstructive
      pulmonary disease.
AB  - Physical activity (PA) and exercise are interrelated but separate concepts. PA
      refers to bodily movement produced by skeletal muscles that results in energy
      expenditure. Exercise is a subset of PA, in which generally higher levels of
      muscular activity are performed for a purpose, such as achieving physical fitness
      or winning a sporting contest. Higher exercise capacity is considered to be
      permissive of greater PA in the home and community settings. Individuals with
      chronic obstructive pulmonary disease (COPD) are physically inactive when
      compared with healthy age-matched control subjects. Furthermore, physical
      inactivity is independently associated with adverse outcome in patients with
      COPD, including more rapid disease progression, impaired health status, and
      increased health care utilization and mortality risk. While there are several
      methods to objectively measure PA, recent scientific studies have commonly
      utilized questionnaires and activity monitors. The latter include simple
      pedometers and complex accelerometers, which can measure and record movement in
      up to 3 planes. In COPD, multiple patient characteristics and disease severity
      markers are related to activity level, including pulmonary physiological
      abnormalities such as airway obstruction and hyperinflation; exercise capacity
      such as the 6-minute walking distance; exacerbations of respiratory disease; and
      comorbid conditions. Clinical trials of bronchodilators, supplemental oxygen
      therapy, exercise training or pulmonary rehabilitation, or PA counseling have
      provided inconsistent results in demonstrating increased PA from the interaction.
      This is probably because the phenomenon of physical inactivity is complex,
      resulting not only from physiological impairments, but symptoms, cultural,
      motivational, and environmental factors. 

PMID- 26307103
TI  - Selective repression of RET proto-oncogene in medullary thyroid carcinoma by a
      natural alkaloid berberine.
AB  - BACKGROUND: The gain-of-function mutation of the RET proto-oncogene, which
      encodes a receptor tyrosine kinase, is strongly associated with the development
      of several medullary thyroid carcinomas (MTCs). Thus, the RET protein has been
      explored as an excellent target for progressive and advanced MTC. In this study
      we have demonstrated a therapeutic strategy for MTC by suppressing the
      transcription of RET proto-oncogene though the stabilization of G-quadruplex
      structure formed on the promoter region of this gene using a natural product
      berberine. METHODS: Medullary thyroid carcinoma (MTC) TT cell line has been used
      to evaluate the effects of berberine on RET expression and its downstream
      signaling pathways. The specificity of berberine was demonstrated by using the
      papillary thyroid carcinoma TPC1 cell line, which lacks the G-quadruplex forming
      sequence on the RET promoter region due to chromosomal rearrangement. RESULTS:
      Berberine suppressed the RET expression by more than 90 % in MTC TT cells at a
      concentration of 2.5 MUg/ml with minimal effect on the TPC1 cells. Canadine,
      which is a structural analogue of berberine, showed little interaction with RET G
      quadruplex and also had no effect on RET expression in MTC TT cells. The down
      regulation of RET with berberine further inhibited the cell proliferation through
      cell cycle arrest and activation of apoptosis in TT cells, which was confirmed by
      a 2-fold increase in the caspase-3 activity and the down-regulation of cell-cycle
      regulatory proteins. CONCLUSION: Our data strongly suggest that the G-quadruplex
      forming region and the stabilization of this structure play a critical role in
      mediating the repressive effect of berberine on RET transcription.

PMID- 26307104
TI  - The relationship between fasting plasma glucose and MPO in patients with acute
      coronary syndrome.
AB  - BACKGROUND: Inflammation plays a critical role in the progression of
      atherosclerosis, and hyperglycemia is a common feature in patients with ACS. We
      investigated the relationship between fasting plasma glucose (FPG) levels and the
      levels of the inflammatory factor, myeloperoxidase (MPO), in patients with acute
      coronary syndrome (ACS). METHOD: A total of 85 patients with no prior history of
      diabetes mellitus were recruited. The patients were divided into three groups
      based on their FPG levels as follows: group A, FPG < 5.6 mmol/l; group B, 5.6
      mmol/l <= FPG < 6.1 mmol/l; and group C, FPG >= 6.1 mmol/l. The FPG
      concentrations and plasma MPO levels were determined, coronary angioplasty was
      performed, and the Gensini scores were used to evaluate the severity of the
      coronary lesion. The MPO expression in peripheral blood mononuclear cells (PBMCs)
      in patients with ACS was determined using western blot analysis. RESULT: The
      results demonstrated that the levels of FPG were significantly and positively
      correlated with plasma MPO levels, Gensini scores, high sensitive C reaction
      protein(hs-CRP)levels, leukocyte and neutrophils count. In multivariate
      regression analyses the FPG levels were positively correlated with plasma MPO
      levels, Gensini score and hs-CRP. The plasma MPO levels in the group C
      [68.68(52.62-91.88) U/L] were significantly higher than in the group A
      [63.04(26.18-97.75) U/L] and group B [58.22(23.95-89.54) U/L]. The plasma hs-CRP
      concentrations are also higher in group C [42.28 (0.31-169.40) mg/L] than in the
      group A [12.51(0.28-176.25) mg/L] and group B [14.7 (0.14-89.68) mg/L].
      CONCLUSION: This study demonstrates that FPG values are positively correlated
      with plasma MPO levels, suggesting MPO may play a role in the proatherogenesis of
      high FPG.

PMID- 26307106
TI  - Perioperative anticoagulant management in patients with atrial fibrillation :
      practical implications of recent clinical trials.
AB  - Defining the safest perioperative anticoagulation management approach for
      patients who are receiving chronic anticoagulant therapy stroke prevention has
      been a challenging and longstanding dilemma, especially for patients with atrial
      fibrillation who constitute the most common patient group receiving long term
      anticoagulation. Using a case-based format, we summarize the findings of recent
      clinical trialswhich have helped to informed best practices for perioperative
      anticoagulant management in patients with atrial fibrillation and provide an
      algorithmic management approach to this problem. We have done so by exploring the
      evidence to address 3 key questions: Is it necessary to interrupt anticoagulation
      for a procedure? How to estimate a patient's risk for perioperative
      thromboembolism and bleeding? If chronic anticoagulation interruption is
      required, is bridging anticoagulation with heparin needed? 

PMID- 26307105
TI  - Comparison of physical interventions, behavioral interventions, natural health
      products, and pharmacologics to manage hot flashes in patients with breast or
      prostate cancer: protocol for a systematic review incorporating network meta
      analyses.
AB  - BACKGROUND: Breast and prostate cancers are the most commonly diagnosed non
      dermatologic malignancies in Canada. Agents including endocrine therapies (e.g.,
      aromatase inhibitors, gonadotrophin-releasing hormone analogs, anti-androgens,
      tamoxifen) and chemotherapy have improved survival for both conditions. As
      endocrine manipulation is a mainstay of treatment, it is not surprising that hot
      flashes are a common and troublesome adverse effect. Hot flashes can cause
      chills, night sweats, anxiety, and insomnia, lessening patients' quality of life.
      These symptoms impact treatment adherence, worsening prognosis. While short-term
      estrogen replacement therapy is frequently used to manage hot flashes in healthy
      menopausal women, its use is contraindicated in breast cancer. Similarly,
      testosterone replacement therapy is contraindicated in prostate cancer. It is
      therefore not surprising that non-hormonal pharmacological treatments (anti
      depressants, anti-epilectics, anti-hypertensives), physical/behavioral treatments
      (e.g., acupuncture, yoga/exercise, relaxation techniques, cognitive behavioral
      therapy), and natural health products (e.g., black cohosh, flax, vitamin E,
      ginseng) have been studied for control of hot flashes. There is a need to
      identify which interventions minimize the frequency and severity of hot flashes
      and their impact on quality of life. This systematic review and network meta
      analysis of randomized studies will synthesize available evidence addressing this
      knowledge gap. METHODS/DESIGN: An electronic search of Medline, Embase, AMED,
      PsycINFO, and the Cochrane Register of Controlled Trials has been designed by an
      information specialist and peer reviewed by a second information specialist.
      Study selection and data collection will be performed by two reviewers
      independently. Risk of bias assessments will be completed using the Cochrane Risk
      of Bias Scale. Outcomes of interest will include validated measures of hot flash
      severity, hot flash frequency, quality of life, and harms. Bayesian network meta
      analyses will be performed where judged appropriate based on review of clinical
      and methodologic features of included studies. DISCUSSION: Our review will
      include a broad range of interventions that patients with breast and prostate
      cancer have attempted to use to manage hot flashes. Our work will establish the
      extent of evidence underlying these interventions and will employ an inclusive
      approach to analysis to inform comparisons between them. Our findings will be
      shared with Cancer Care Ontario for consideration in the development of guidance
      related to supportive care in these patients. SYSTEMATIC REVIEW REGISTRATION: 
      PROSPERO: CRD42015024286.

PMID- 26307107
TI  - Helmets for Kids: evaluation of a school-based helmet intervention in Cambodia.
AB  - OBJECTIVE: This paper analyses helmet use before and after implementing Helmets
      for Kids, a school-based helmet distribution and road safety programme in
      Cambodia. METHODS: Nine intervention schools (with a total of 6721 students) and
      four control schools (with a total of 3031 students) were selected using
      purposive sampling to target schools where students were at high risk of road
      traffic injury. Eligible schools included those where at least 50% of students
      commute to school on bicycles or motorcycles, were located on a national road
      (high traffic density), had few or no street signs nearby, were located in an
      area with a history of crash injuries and were in a province where other Cambodia
      Helmet Vaccine Initiative activities occur. Programme's effectiveness at each
      school was measured through preintervention and postintervention roadside helmet
      observations of students as they arrived or left school. Research assistants
      conducted observations 1-2 weeks preintervention, 1-2 weeks postintervention, 10
      12 weeks postintervention and at the end of the school year (3-4 months
      postintervention). RESULTS: In intervention schools, observed student helmet use
      increased from an average of 0.46% at 1-2 weeks preintervention to an average of
      87.9% at 1-2 weeks postintervention, 83.5% at 10-12 weeks postintervention and
      86.5% at 3-4 months postintervention, coinciding with the end of the school year.
      Increased helmet use was observed in children commuting on bicycle or motorcycle,
      which showed similar patterns of helmet use. Helmet use remained between 0.35%
      and 0.70% in control schools throughout the study period. CONCLUSIONS: School
      based helmet use programmes that combine helmet provision and road safety
      education might increase helmet use among children.

PMID- 26307108
TI  - Pneumonia among adults hospitalized with laboratory-confirmed seasonal influenza
      virus infection-United States, 2005-2008.
AB  - BACKGROUND: Influenza and pneumonia combined are the leading causes of death due
      to infectious diseases in the United States. We describe factors associated with
      pneumonia among adults hospitalized with influenza. METHODS: Through the Emerging
      Infections Program, we identified adults >= 18 years, who were hospitalized with
      laboratory-confirmed influenza during October 2005 through April 2008, and had a
      chest radiograph (CXR) performed. Pneumonia was defined as the presence of a CXR
      infiltrate and either an ICD-9-CM code or discharge summary diagnosis of
      pneumonia. RESULTS: Among 4,765 adults hospitalized with influenza, 1392 (29 %)
      had pneumonia. In multivariable analysis, factors associated with pneumonia
      included: age >= 75 years, adjusted odds ratio (AOR) 1.27 (95 % confidence
      interval 1.10-1.46), white race AOR 1.24 (1.03-1.49), nursing home residence AOR
      1.37 (1.14-1.66), chronic lung disease AOR 1.37 (1.18-1.59), immunosuppression
      AOR 1.45 (1.19-1.78), and asthma AOR 0.76 (0.62-0.92). Patients with pneumonia
      were significantly more likely to require intensive care unit (ICU) admission (27
      % vs. 10 %), mechanical ventilation (18 % vs. 5 %), and to die (9 % vs. 2 %).
      CONCLUSIONS: Pneumonia was present in nearly one-third of adults hospitalized
      with influenza and was associated with ICU admission and death. Among patients
      hospitalized with influenza, older patients and those with certain underlying
      conditions are more likely to have pneumonia. Pneumonia is common among adults
      hospitalized with influenza and should be evaluated and treated promptly.

PMID- 26307109
TI  - Mid-term clinical results of primary total knee arthroplasty using metal block
      augmentation and stem extension in patients with rheumatoid arthritis.
AB  - BACKGROUND: Despite recent advancements in rheumatoid arthritis (RA)
      pharmacotherapy, surgeons still encounter severely damaged knees. The purpose of
      the present study was to analyze the mid-term clinical results of total knee
      arthroplasty (TKA) with metal block augmentation and stem extension. METHODS: A
      total of 26 knees in 21 patients who underwent primary TKA with metal block
      augmentation and stem extension were retrospectively reviewed. All patients with
      a mean age of 63 years had RA for a mean duration of 15 years. Functional and
      radiographic results as well as complications were evaluated at the mean follow
      up period of 6 years after TKA. Eight knees were lost follow-up after the two
      year evaluation. RESULTS: Tibial bone defects with average depth of 19 mm were
      preoperatively recognized in all 26 knees. The postoperative joint line was
      reconstructed on average 11 mm above the fibular head using average thickness of
      11 mm tibial inserts and 9 mm metal blocks with stem extension. Significant
      improvements (p < 0.05 for all comparisons) were observed postoperatively in
      maximum extension angle from -10 degrees  to -1 degrees , range of motion from
      101  degrees  to 115  degrees , and Knee Society Score (knee score/function
      score) from 35/18 to 90/64. Non-progressive radiolucent lines beneath the metal
      block and osteosclerotic changes around the medullary stem were found in 16 knees
      (62%) and 14 knees (54%), respectively. There was two failures (8%): fragile
      supracondylar femur fractures and knee instability. No knees showed any
      radiographic implant loosening, dislocation, polyethylene insert breakage,
      peroneal palsy, or infection. CONCLUSIONS: Primary TKA with metal block
      augmentation and stem extension could effectively restore function in RA patients
      with advanced forms of knee joint destruction, and be reliable and durable for a
      mean postoperative period of 6 years. Further study is needed to determine the
      long-term results of TKA using metal block augmentation and stem extension.

PMID- 26307110
TI  - Patients with atrial fibrillation and low risk of stroke: do they really need
      anticoagulation?
AB  - Atrial fibrillation (AF) significantly increases the risk of thromboembolic
      events, in particular the risk of stroke. Anticoagulation therapy has been shown
      to reduce this risk; therefore, the treatment should be lifelong. However, the
      risk in patients with nonvalvular AF is not equally distributed, and there is a
      population of patients at low risk. According to the current guidelines, the
      decision on the need of anticoagulation is primarily dependent on whether the
      patient is at low risk. The CHA2DS2-VASc is currently the most commonly
      recommended scheme for assessing thromboembolic risk in patients with nonvalvular
      AF. In a large group of nontreated patients with a CHA2DS2-VASc of 0 (1 in
      women), the annual risk of stroke was 0.49%; ischemic stroke, 0.43%; bleeding,
      1.08%; intracranial bleeding, 0.15%; and death, 3.87%. In patients on warfarin,
      the frequency of ischemic stroke was similar. Patients with a CHA2DS2-VASc of 0
      (1 in women) are low-risk patients who do not benefit from anticoagulation. The
      low-risk group is also defined as patients younger than 65 years of age without
      structural cardiovascular disease, regardless of sex. They represent from 6% to
      10% of patients with nonvalvular AF. Thromboembolic risk in patients with a score
      of 1 (2 in women) is much more controversial, as reflected by several recently
      published cohort studies. In a Swedish study, the risk was found to be low, while
      in Danish and Taiwanese studies-as significantly higher. Another analysis has
      shown that the use of vitamin K antagonists is appropriate when the risk of
      stroke is higher than 1.7%/year. Owing to a lower risk of intracranial bleeding,
      anticoagulation with nonvitamin K antagonist oral anticoagulants may be
      considered already at an annual risk of stroke exceeding 0.9%. Patients at low
      risk do not require chronic anticoagulation. 

PMID- 26307111
TI  - Associations of the Insertion/Deletion Polymorphism in the ACE Gene and Risk of
      Gastric Cancer: A Meta-Analysis.
AB  - BACKGROUND: Reported associations of ACE polymorphisms with gastric cancer have
      been inconsistent, prompting a meta-analysis of 12 published case-control studies
      where we estimated risk (odds ratio [OR]). METHODS: We searched MEDLINE through
      PubMed and EMBASE for suitable articles that had case-control design with gastric
      cancer as outcome. In this meta-analysis, our overall findings were subjected to
      modifier analyses (outlier and sensitivity treatments). We also performed
      subgroup analysis based on ethnicity (German and Japanese) and histological
      subtype (intestinal and diffuse). RESULTS: Significance of the protective effects
      among homozygote carriers of the II genotype (OR 0.54-0.63, P = 0.01-0.02)
      disappeared with outlier analysis (OR 0.81-0.88, P = 0.12-0.14). Among DD
      homozygotes, this treatment altered the direction of association from weak
      protection (OR 0.95-0.96, P = 0.79-0.82) to increased risk (OR 1.13-1.19, P =
      0.14-0.16). No significant associations were observed among ID genotype carriers
      (OR 0.91-0.94, P = 0.69-0.72). Japanese pooled effects varied across the genotype
      comparisons (OR 0.93-1.06, P = 0.54-0.72). Sensitivity treatment demonstrated
      robustness of the II genotype, but not the other two, both in overall and
      subgroup analyses. Histological subtype analysis yielded protection from
      intestinal cancer across the comparisons (OR 0.38-0.71, P = 0.15-0.50) but
      variable results for the diffuse type (OR 0.59-1.32, P = 0.19-0.92). CONCLUSION:
      In summary, carriers of the ACE II genotype appear to be protected from gastric
      cancer, regardless of ethnicity or tumor type.

PMID- 26307112
TI  - Using non-targeted direct analysis in real time-mass spectrometry (DART-MS) to
      discriminate seeds based on endogenous or exogenous chemicals.
AB  - Forage seeds are a highly traded agricultural commodity, and therefore, quality
      control and assurance is high priority. In this study, we have used direct
      analysis in real time-mass spectrometry (DART-MS) as a tool to discriminate
      forage seeds based on their non-targeted chemical profiles. In the first
      experiment, two lots of perennial ryegrass (Lolium perenne L.) seed were
      discriminated based on exogenous residues of N-(3, 4-dichlorophenyl)-N,N
      dimethylurea (Diuron(TM)), a herbicide. In a separate experiment, washed and
      unwashed seeds of the forage legumes white clover (Trifolium repens L.) and
      alfalfa (Medicago sativa L.) were discriminated based on the presence or absence
      of oxylipins, a class of endogenous antimicrobial compounds. Unwashed seeds
      confer toxicity towards symbiotic, nitrogen-fixing rhizobia which are routinely
      coated on legume seeds before planting, resulting in reduced rhizobial count.
      This is the first report of automatic introduction of intact seeds in the DART
      ion source and detecting oxylipins using DART-MS. Apart from providing scope to
      investigate legume-rhizobia symbiosis further in the context of oxylipins, the
      results presented here will enable future studies aimed at classification of
      seeds based on chemicals bound to the seed coat, thereby offering an efficient
      screening device for industry. 

PMID- 26307113
TI  - Development of a recombinant Arxula adeninivorans cell bioassay for the detection
      of molecules with progesterone activity in wastewater.
AB  - This study describes the development of a bioassay to detect the presence of
      progesterone and progesterone-like molecules in wastewater samples. The basis of
      the bioassay is the integration of the human progesterone receptor gene into the
      yeast Arxula adeninivorans for the constitutive synthesis of the receptor. After
      incubation, binding of the analyte to the receptor induces the production of a
      reporter protein. Two reporter proteins were compared for detection parameters
      such as half-maximal activity (EC50), limit of detection (LoD) and limit of
      quantification (LoQ). When the extracellular phytase K was used, an EC50 value of
      155 ng L(-1) and a LoD of 27 ng L(-1) progesterone were obtained after 4 h
      incubation, while use of the fluorescent dsRED as the reporter protein, resulted
      in an EC50 of 320 ng L(-1) and a LoD of 65 ng L(-1) after 20 h incubation. Use of
      phytase K as the reporter protein offers decreased incubation time and increased
      sensitivity; however the dsRED reporter system is less labor-intensive.
      Additionally, the affinity of known agonists and antagonists of the human
      progesterone receptor was determined. The utility of this bioassay was confirmed
      by measuring total progesterone equivalent concentration of samples from a
      wastewater treatment plant. The A. adeninivorans-based transactivation assay was
      able to measure concentrations of about 311 ng L(-1) in the influent stream but
      could not detect progesterone activity in effluent. One key feature of the assay
      is the robustness of A. adeninivorans, which allows sample measurement without
      any sample preparation. 

PMID- 26307114
TI  - Novel MEN 1 gene findings in rare sporadic insulinoma--a case control study.
AB  - BACKGROUND: Insulinomas, which are rare tumors causing hyperinsulinemic
      hypoglycemia are usually sporadic but may also occur in association with multiple
      endocrine neoplasia type 1 (MEN-1) syndrome an autosomal dominant disorder caused
      by MEN1 gene mutations. MEN1 encodes a nuclear protein Menin, a tumor suppressor
      which acts as an adapter and interacts with partner proteins involved in crucial
      activities like transcriptional regulation, cell division, proliferation and
      genome stability. This study reports on clinical findings and mutation screening
      in sporadic insulinoma patients. METHODS: Seventeen patients diagnosed with
      insulinoma were recruited along with 30 healthy volunteers who acted as controls
      for the present study. The patients presented with symptoms of sweating, tremors,
      drowsiness, palpitations, loss of consciousness, abnormal behavior, seizures and
      weight gain. Detailed clinical and family history was collected from all the
      participants along with 5 ml of blood sample after taking informed consent.
      Genomic DNA isolated from blood was subjected to MEN1 gene amplification followed
      by direct sequencing. Nucleotide sequences obtained were compared with published
      MEN1 cDNA sequences. Prediction of functional effects of novel changes was done
      using various bioinformatics algorithms. RESULTS: Molecular analysis revealed
      presence of three novel exonic mutations (M561K, Q192K and Q261Q), two novel
      intronic variations c.445-44G -> A and c.913-42G -> C in introns two and six
      respectively and three reported exon SNPs; H433H (rs540012), D418D (rs2071313),
      A541T (rs2959656) and one intronic SNP (rs669976). CONCLUSIONS: The study
      identified presence of novel pathogenic MEN1 mutations in sporadic cases of
      insulinoma. The new mutations identified were in regions involved in defective
      binding of menin to proteins implicated in genetic and epigenetic mechanisms. The
      outcome of the study extends the growing list of MEN1 pathogenic mutations even
      in sporadic cases providing consequential insight into phenotypic heterogeneity
      and in the expression of individual mutations.

PMID- 26307115
TI  - The occurrence of antibodies against Legionella pneumophila in patients with
      autoimmune rheumatic diseases.
AB  - INTRODUCTION: Patients with autoimmune rheumatic diseases are more susceptible to
      infection, owing to the underlying disease itself or to its treatment. Most
      commonly, infections affect the respiratory and urinary tracts. One of the
      etiological factors of infections in these patients is the bacteria of the genus
      Legionella. OBJECTIVES: The aim of the study was to assess the prevalence of anti
      Legionella pneumophila (L. pneumophila) antibodies in patients with autoimmune
      rheumatic diseases and to analyze individual and environmental risk factors for
      the development of Legionella infection in patients with positive antibody
      results. PATIENTS AND METHODS: The study group consisted of 165 patients with
      autoimmune rheumatic diseases and 100 healthy subjects. Serum samples were tested
      for the presence of specific antibodies in the immunoglobulin (Ig) M and IgG
      classes against L. pneumophila serogroups 1 to 7 (SG 1-7) and the IgG class for
      serogroup 1 (SG 1). RESULTS: Antibodies against L. pneumophila were found in 7
      patients (4%): 5 cases with antibody positivity only in the IgG class and 2 cases
      with antibody positivity in both classes. In patients with positive IgG
      antibodies for SG 1-7, specific antibodies for L. pneumophila SG 1 were not
      detected. In the control group, positive results were obtained in 9 cases (9%):
      IgM positivity in 6 (6%) and IgG positivity in 3 (3%). CONCLUSIONS: The frequency
      of antibodies to L. pneumophila in our patients is comparable to that in healthy
      individuals. L. pneumophila should be recognized as a potential pathogen in
      patients with autoimmune rheumatic diseases. Primary disease condition,
      immunosuppressive therapy, and other risk factors should not be ignored in these
      patients.

PMID- 26307117
TI  - Solvent Effects on Acrylate kp in Organic Media: A Response.
AB  - Radical propagation rate is adequately understood in the light of fundamental
      kinetic theory. Differences in bulk and solution k(p) are primarily of entropic
      origin, with the effects depending on the differences in polarity and size of
      monomer and solvent molecules, respectively. Experimental data for the
      propagation rate coefficient of secondary acrylate radicals demonstrate that bulk
      and solution-in-toluene k(p) exhibit distinctly different behavior. Bulk k(p) is
      clearly enhanced in passing from methyl acrylate (MA) to dodecyl acrylate (DA),
      whereas solution-in-toluene k(p) is approximately constant with a slight tendency
      to decrease from MA to DA. This kp behavior has also been found in a recent
      study, in which it has, however, been concluded that k(p) in solution of toluene
      (and of butyl acetate) displays a similar behavior to bulk. This surprising and
      ina-dequate conclusion requires the present comment and rectification to be made.

PMID- 26307116
TI  - MicroRNA-155-5p is associated with oral squamous cell carcinoma metastasis and
      poor prognosis.
AB  - BACKGROUND: Abnormal miRNA expression was recently implicated in the metastasis
      of oral squamous cell carcinoma (OSCC) and with a poor prognosis. The initiation
      of the invasion-metastasis cascade involves epithelial-mesenchymal transition
      (EMT). Our aim was to clarify how miRNA, especially miR-155-5p misexpression
      contributes to OSCC metastasis through EMT. METHODS: We collected tumor samples
      from 73 subjects with OSCC. The samples were analyzed by quantitative reverse
      transcription polymerase chain reaction (qRT-PCR), and correlations between miR
      155-5p levels and clinical characteristics were investigated. OSCC cell lines
      were analyzed by miRNA microarray and by transfection with a miR-155-5p mimic or
      inhibitor, followed by proliferation and wound-healing migration assays. qRT-PCR
      analyses of EMT makers in cells transfected with miR-155-5p inhibitor were
      performed. RESULTS: We found high miR-155-5p expression in tissue samples from
      subjects with OSCC that had metastasized to cervical lymph nodes. HSC-3 cells
      also strongly expressed miR-155-5p. The epithelial marker E-cadherin was strongly
      expressed in HSC-3 cells transfected with miR-155-5p inhibitor, and we observed
      elevated SOCS1 and decreased STAT3 expression in these cells. CONCLUSIONS: Our
      results suggest that miR-155-5p causes OSCC to metastasize, and could serve as a
      novel therapeutic target for OSCC.

PMID- 26307118
TI  - Standardization of Sonographic Lung-to-Head Ratio Measurements in Isolated
      Congenital Diaphragmatic Hernia: Impact on the Reproducibility and Efficacy to
      Predict Outcomes.
AB  - OBJECTIVES: The purpose of this study was to evaluate the impact of
      standardization of the lung-to-head ratio measurements in isolated congenital
      diaphragmatic hernia on prediction of neonatal outcomes and reproducibility.
      METHODS: We conducted a retrospective cohort study of 77 cases of isolated
      congenital diaphragmatic hernia managed in a single center between 2004 and 2012.
      We compared lung-to-head ratio measurements that were performed prospectively in
      our institution without standardization to standardized measurements performed
      according to a defined protocol. RESULTS: The standardized lung-to-head ratio
      measurements were statistically more accurate than the nonstandardized
      measurements for predicting neonatal mortality (area under the receiver operating
      characteristic curve, 0.85 versus 0.732; P = .003). After standardization, there
      were no statistical differences in accuracy between measurements regardless of
      whether we considered observed-to-expected values (P > .05). Standardization of
      the lung-to-head ratio did not improve prediction of the need for extracorporeal
      membrane oxygenation (P> .05). Both intraoperator and interoperator
      reproducibility were good for the standardized lung-to-head ratio (intraclass
      correlation coefficient, 0.98 [95% confidence interval, 0.97-0.99]; bias, 0.02
      [limits of agreement, -0.11 to +0.15], respectively). CONCLUSIONS:
      Standardization of lung-to-head ratio measurements improves prediction of
      neonatal outcomes. Further studies are needed to confirm these results and to
      assess the utility of standardization of other prognostic parameters.

PMID- 26307120
TI  - A Model Using Texture Features to Differentiate the Nature of Thyroid Nodules on
      Sonography.
AB  - OBJECTIVES: To evaluate the use of texture-based gray-level co-occurrence matrix
      (GLCM) features extracted from thyroid sonograms in building prediction models to
      determine the nature of thyroid nodules. METHODS: A GLCM was used to extract the
      texture features of 155 sonograms of thyroid nodules (76 benign and 79
      malignant). The GLCM features included energy, contrast, correlation, sum of
      squares, inverse difference moment, sum average, sum variance, sum entropy,
      entropy, difference variance, difference entropy, information measures of
      correlation, and maximal correlation coefficient. The texture features extracted
      by the GLCM were used to build 6 different statistical models, including support
      vector machine, random tree, random forest, boost, logistic, and artificial
      neural network models. The models' performances were evaluated by 10-fold cross
      validation combining a receiver operating characteristic curve, indices of
      accuracy, true-positive rate, false-positive rate, sensitivity, specificity,
      precision, recall, F-measure, and area under the receiver operating
      characteristic curve. External validation was used to examine the stability of
      the model that showed the best performance. RESULTS: The logistic model showed
      the best performance, according to 10-fold cross-validation, among the 6 models,
      with the highest area under the curve (0.84), accuracy (78.5%), true-positive
      rate (0.785), sensitivity (0.789), specificity (0.785), precision (0.789), recall
      (0.785), and F-measure (0.784), as well as the lowest false-positive rate
      (0.215). The external validation results showed that the logistic model was
      stable. CONCLUSIONS: Gray-level co-occurrence matrix texture features extracted
      from sonograms of thyroid nodules coupled with a logistic model are useful for
      differentiating between benign and malignant thyroid nodules.

PMID- 26307119
TI  - Sensitivity and Specificity of the Toe-Brachial Index for Detecting Peripheral
      Arterial Disease: Initial Findings.
AB  - OBJECTIVES: The toe-brachial index (TBI) is an alternative to the ankle-brachial
      index (ABI) in screening for peripheral arterial disease (PAD); however, there is
      limited evidence comparing their diagnostic accuracy. This study compared the
      diagnostic accuracy of the ABI and TBI in a population at risk of PAD. METHODS:
      The sensitivity and specificity of the ABI and TBI were determined by color
      duplex sonography. Receiver operating characteristic (ROC) analysis was
      performed. RESULTS: A total of 119 participants were recruited (75 male and 44
      female). The sensitivity for PAD was highest for the TBI (71%; ABI, 45%), and the
      specificity was highest for the ABI (93%; TBI, 78%). Receiver operating
      characteristic analysis indicated that the TBI (ROC area, 0.77; P = .0001) had
      greater clinical efficacy for diagnosis of PAD than the ABI (ROC area, 0.65; P =
      .005). CONCLUSIONS: In specific populations, the TBI may have greater clinical
      efficacy than the ABI for diagnosis of PAD.

PMID- 26307121
TI  - Role of 3-Dimensional Sonography in Detection of a Foreign Body as a Cause of
      Chronic Pelvic Pain.

PMID- 26307122
TI  - Prognostic Value of Diagnostic Sonography in Patients With Plantar Fasciitis.
AB  - OBJECTIVES: The primary objective of this study was to determine whether the
      sonographic appearance of the plantar fascia is predictive of the treatment (ie,
      pain) response in patients receiving supportive therapy for proximal plantar
      fasciitis. This study was a secondary analysis of data obtained from a randomized
      controlled trial of ambulatory adults, which examined the efficacy of 3 different
      foot supports for plantar fasciitis. METHODS: Participants underwent diagnostic
      sonographic examinations of their heel at baseline and again at 3 months by a
      single experienced foot and ankle surgeon. Quantitative (eg, thickness) and
      qualitative (eg, biconvexity) characteristics of the fascia were recorded
      according to a standard protocol. Logistic regression models were used to
      identify predictors of the pain response. RESULTS: Seventy patients completed a
      baseline evaluation, and 63 patients completed a 3-month follow-up assessment.
      The pain response was not associated with the type of foot support (P> .05). The
      only significant indicator of an unfavorable response in the univariate and
      multivariate analyses was biconvexity of the plantar fascia on sonography at
      presentation (multivariate odds ratio, 4.76 [95% confidence interval, 1.16-19.5;
      P= .030). Furthermore, changes in self-reported pain over the 3-month study
      period were not accompanied by alterations in plantar fascia thickness over this
      time (r = .056; P = .671). CONCLUSIONS: We conclude that patients who present
      with biconvexity of the plantar fascia may be less responsive to tier 1 treatment
      regimens that center around mechanical support of the plantar fascia.
      Furthermore, follow-up measurements of the fascia in this population should not
      weigh heavily in decisions such as return to play.

PMID- 26307123
TI  - Approach to the Swollen Arm With Chronic Dialysis Access: It's Not Just Deep Vein
      Thrombosis.
AB  - The purposes of this pictorial essay are as follows: (1) Review a systematic
      approach to using sonography in the initial evaluation of patients with acute arm
      swelling and permanent dialysis access. (2) Identify normal grayscale and Doppler
      findings in arteriovenous fistulas and grafts. (3) Discuss a spectrum of vascular
      differential diagnoses for arm swelling in this setting, including stenosis of
      the access, draining vein complications, thrombosis, steal syndrome, and
      aneurysms, as well as several nonvascular causes. (4) Recognize findings that
      warrant further imaging evaluation or intervention. 

PMID- 26307124
TI  - Visual Estimation of the Severity of Aortic Stenosis and the Calcium Burden by 2
      Dimensional Echocardiography: Is It Reliable?
AB  - OBJECTIVES: Guidelines have recommended aortic valve surgery in asymptomatic
      patients with severe aortic stenosis and a large aortic valve calcium burden. The
      purpose of this study was to determine whether visual assessment of aortic valve
      calcium and stenosis severity are reliable based on 2-dimensional
      echocardiography alone. METHODS: We prospectively enrolled 68 patients with
      aortic stenosis and compared them with 30 control participants without aortic
      stenosis. All had aortic valve calcium score assessment by computed tomography.
      In a random order, 2-dimensional images without hemodynamic data were
      independently reviewed by 2 level 3-trained echocardiographers, who then
      classified these patients into categories based on aortic valve calcium and
      stenosis severity. RESULTS: The 68 patients (mean age +/- SD, 74 +/- 10 years)
      were classified as having mild (n = 28), moderate (n = 22), and severe (n = 18)
      aortic stenosis. When the observers were asked to grade the degree of valve
      calcification, the agreement between them was poor (kappa = 0.33-0.39). The
      visual ability to determine stenosis severity compared with Doppler
      echocardiography had high specificity (81% and 88% for observers 1 and 2).
      However, sensitivity was unacceptably low (56%-67%), and the positive predictive
      value was poor (44%-50%). Agreement was fair (kappa= 0.58-0.69) between the
      observers for determining severe stenosis. CONCLUSIONS: Our results suggest that
      visual assessment of aortic valve calcium has high interobserver variability; the
      visual ability to determine severe aortic stenosis has low sensitivity but high
      specificity. Our results may have important implications for treatment of
      patients with aortic stenosis and guiding the use of handheld echocardiography.
      Further research with larger cohorts is needed to validate the variability,
      sensitivity, and specificity reported in our study.

PMID- 26307125
TI  - Polymorphisms within the human leucocyte antigen-E gene and their associations
      with susceptibility to rheumatoid arthritis as well as clinical outcome of anti
      tumour necrosis factor therapy.
AB  - Involvement of the non-classical human leucocyte antigen-E (HLA-E) in both innate
      and acquired immune response suggests its possible role in development of
      autoimmune pathologies. This study was undertaken to investigate relationships
      between the HLA-E gene single nucleotide polymorphisms (SNPs) and a risk of
      rheumatoid arthritis (RA), as well as to evaluate a potential of these
      polymorphisms to modulate clinical outcome of anti-tumour necrosis factor (TNF)
      treatment in female patients. A total of 223 female patients with RA receiving
      anti-TNF biological therapy and 134 female healthy subjects were enrolled into
      the study. Genotypings for two SNPs within the HLA-E gene (rs1264457 HLA
      E*01:01/01:03; rs1059510 HLA-E*01:03:01/01:03:02) were performed using a
      polymerase chain reaction (PCR) amplification employing LightSNiP assays.
      Clinical response was evaluated according to the European League Against
      Rheumatism (EULAR) criteria at 12 and 24 weeks after initiation of the therapy.
      The frequency of the HLA-E*01:01/01:01 genotype was decreased significantly in RA
      patients in comparison to controls (P = 0.031). The presence of the HLA
      E*01:01/01:01 genotype in patients correlated with better EULAR response after 12
      weeks of anti-TNF treatment, while 01:03 allele carriers were generally
      unresponsive to the treatment (P = 0.014). The HLA-E*01:03/01:03 genotype was
      also over-represented among non-responding patients in comparison to HLA
      E*01:01/01:01 homozygotes (P = 0.021). With respect to the HLA-E rs1059510
      variation, a better response after 12 weeks was observed more frequently in
      patients carrying the HLA-E*01:03:01/01:03:01 genotype than other genotypes (P =
      0.009). The results derived from this study imply that HLA-E polymorphisms may
      influence RA susceptibility and affect clinical outcome of anti-TNF therapy in
      female RA patients.

PMID- 26307126
TI  - Neuroacanthocytosis: A new mutation.

PMID- 26307127
TI  - Death and kidney allograft dysfunction after bacteremia.
AB  - BACKGROUND: Some studies have reported causal associations between bacteremia and
      mortality or allograft loss in kidney transplant recipients (KTR). However, few
      studies have assessed the clinical course of kidney function and the risk of
      acute allograft rejection after bacteremia. METHODS: We retrospectively reviewed
      902 kidney transplants performed at Nagoya Daini Red Cross Hospital between
      January 1, 2002 and March 31, 2014. Forty-five living donor kidney transplant
      recipients with single bacteremia were included. We analyzed death, change in
      kidney function, and development of acute allograft rejection 12 months after
      bacteremia according to the following groups: primary source of bacteremia
      (urinary tract or other sources), site of acquisition (community acquired or
      nosocomial), severity (not meeting the systemic inflammatory response syndrome
      criteria and sepsis or severe sepsis and septic shock), empiric antibiotic use
      (appropriate or inappropriate), and baseline kidney function (estimated
      glomerular filtration rate <=44.7 or >=44.8 ml/min). RESULTS: Urinary tract
      infection (UTI) was the leading cause of bacteremia (68.9 %), and Escherichia
      coli was the most common pathogen. Three cases (6.7 %) died of infection that
      caused bacteremia within 12 months. Pneumonia accounted for two-thirds. Kidney
      function declined 1 week after bacteremia (P < 0.05), particularly in severe
      cases. Thereafter, kidney function was comparable to baseline level in each group
      (P >= 0.05). Severe UTI was associated with subsequent acute allograft rejection
      (P = 0.03). CONCLUSIONS: Pneumonia in KTR should be managed with caution. Kidney
      function generally returned to baseline level after bacteremia. However, severe
      UTI may be associated with subsequent acute allograft rejection.

PMID- 26307128
TI  - Lumbar artery injury following renal biopsy.

PMID- 26307129
TI  - Development and Validation of a Short Version of the Kansas City Cardiomyopathy
      Questionnaire.
AB  - BACKGROUND: There is a growing demand to collect patients' experiences of their
      health status (their symptoms, function, and quality of life) in clinical trials,
      quality assessment initiatives, and in routine clinical care. In heart failure,
      the 23-item, disease-specific Kansas City Cardiomyopathy Questionnaire (KCCQ) has
      been shown to be valid, reliable, sensitive to clinical change, and prognostic of
      both clinical events and costs. However, its use has been limited, in part, by
      its length. We sought to develop a shortened version of the instrument that
      maintains the psychometric properties of the full KCCQ. METHODS AND RESULTS:
      Using data from 3 clinical studies incorporating 4168 patients, we derived and
      validated a 12-item KCCQ, the KCCQ-12, to capture symptom frequency, physical and
      social limitations, and quality of life impairment as a result of heart failure,
      as well as an overall summary score. The KCCQ-12 scores had high correlations
      with the original scales (>0.93 for all scales in all clinical settings), high
      test-retest reliability (>0.76 for all domains), high responsiveness (16-31 point
      improvements after discharge from hospitalization; standardized response mean
      =0.61-1.12), and comparable prognostic significance and interpretation of
      clinically important differences as compared with the full KCCQ. CONCLUSIONS: The
      KCCQ-12 is a shorter version of the original 23-item instrument that should be
      more feasible to implement while preserving the psychometric properties of the
      full instrument.

PMID- 26307131
TI  - How to Do More With Less.

PMID- 26307130
TI  - Association of Smoking Status With Angina and Health-Related Quality of Life
      After Acute Myocardial Infarction.
AB  - BACKGROUND: Smoking cessation after acute myocardial infarction (AMI) decreases
      the risk of recurrent AMI and mortality by 30% to 50%, but many patients continue
      to smoke. The association of smoking with angina and health-related quality of
      life (HRQOL) after AMI is unclear. METHODS AND RESULTS: Patients in 2 US
      multicenter AMI registries (n=4003) were assessed for smoking and HRQOL at
      admission and 1, 6, and 12 months after AMI. Angina and HRQOL were measured with
      the Seattle Angina Questionnaire and Short Form-12 Physical and Mental Component
      Scales. At admission, 29% never had smoked, 34% were former smokers (quit before
      AMI), and 37% were active smokers, of whom 46% quit by 1 year (recent quitters).
      In hierarchical, multivariable, regression models that adjusted for
      sociodemographic, clinical and treatment factors, never and former smokers had
      similar and the best HRQOL in all domains. Recent quitters had intermediate HRQOL
      levels, with angina and Short Form-12 Mental Component Scale scores similar to
      never smokers. Persistent smokers had worse HRQOL in all domains compared with
      never smokers and worse Short Form-12 Mental Component Scale scores than recent
      quitters. CONCLUSIONS: Smoking after AMI is associated with more angina and worse
      HRQOL in all domains, whereas smokers who quit after AMI have similar angina
      levels and mental health as never smokers. These observations may help encourage
      patients to stop smoking after AMI.

PMID- 26307134
TI  - Docetaxel Resistance in Prostate Cancer: Taking It Up a Notch.
AB  - Notch signaling is implicated in prostate cancer progression and docetaxel
      resistance. Cui and colleagues describe the additive efficacy and mechanisms of a
      gamma-secretase inhibitor, PF-03084014, and docetaxel in preclinical models of
      prostate cancer, suggesting the need for further clinical development of Notch
      pathway modulators in men with metastatic prostate cancer.

PMID- 26307132
TI  - Who Must We Target Now to Minimize Future Cardiovascular Events and Total
      Mortality?: Lessons From the Surveillance, Prevention and Management of Diabetes
      Mellitus (SUPREME-DM) Cohort Study.
AB  - BACKGROUND: Examining trends in cardiovascular events and mortality in US health
      systems can guide the design of targeted clinical and public health strategies to
      reduce cardiovascular events and mortality rates. METHODS AND RESULTS: We
      conducted an observational cohort study from 2005 to 2011 among 1.25 million
      diabetic subjects and 1.25 million nondiabetic subjects from 11 health systems
      that participate in the Surveillance, Prevention and Management of Diabetes
      Mellitus (SUPREME-DM) DataLink. Annual rates (per 1000 person-years) of
      myocardial infarction/acute coronary syndrome (International Classification of
      Diseases-Ninth Revision, 410.0-410.91, 411.1-411.8), stroke (International
      Classification of Diseases-Ninth Revision, 430-432.9, 433-434.9), heart failure
      (International Classification of Diseases-Ninth Revision, 428-428.9), and all
      cause mortality were monitored by diabetes mellitus (DM) status, age, sex,
      race/ethnicity, and a prior cardiovascular history. We observed significant
      declines in cardiovascular events and mortality rates in subjects with and
      without DM. However, there was substantial variation by age, sex, race/ethnicity,
      and prior cardiovascular history. Mortality declined from 44.7 to 27.1 (P<0.0001)
      for those with DM and cardiovascular disease (CVD), from 11.2 to 10.9 (P=0.03)
      for those with DM only, and from 18.9 to 13.0 (P<0.0001) for those with CVD only.
      Yet, in the [almost equal to]85% of subjects with neither DM nor CVD, overall
      mortality (7.0 to 6.8; P=0.10) and stroke rates (1.6-1.6; P=0.77) did not decline
      and heart failure rates increased (0.9-1.15; P=0.0005). CONCLUSIONS: To sustain
      improvements in myocardial infarction, stroke, heart failure, and mortality,
      health systems that have successfully focused on care improvement in high-risk
      adults with DM or CVD must broaden their improvement strategies to target lower
      risk adults who have not yet developed DM or CVD.

PMID- 26307133
TI  - Copy Number Changes Are Associated with Response to Treatment with Carboplatin,
      Paclitaxel, and Sorafenib in Melanoma.
AB  - PURPOSE: Copy number alterations have been shown to be involved in melanoma
      pathogenesis. The randomized phase III clinical trial E2603: carboplatin,
      paclitaxel, +/- sorafenib (CP vs. CPS) offers a large collection of tumor samples
      to evaluate association of somatic mutations, genomic alterations, and clinical
      outcomes, prior to current FDA-approved therapies. EXPERIMENTAL DESIGN: Copy
      number and mutational analysis on 119 pretreatment samples was performed.
      RESULTS: CPS therapy was associated with improved progression-free survival (PFS)
      compared with CP in patients with tumors with RAF1 (cRAF) gene copy gains (HR,
      0.372; P = 0.025) or CCND1 gene copy gains (HR, 0.45; P = 0.035). CPS therapy was
      associated with improved overall survival (OS) compared with CP in patients with
      tumors with KRAS gene copy gains (HR, 0.25; P = 0.035). BRAF gene copy gain and
      MET amplification were more common in samples with V600K versus V600E mutations
      (P < 0.001), which was validated in The Cancer Genome Atlas (TCGA) dataset.
      CONCLUSIONS: We observed improved treatment response with CPS in patients with
      melanoma whose tumors have RAF1 (cRAF), KRAS, or CCND1 amplification, all of
      which can be attributed to sorafenib targeting CRAF. These genomic alterations
      should be incorporated in future studies for evaluation as biomarkers.

PMID- 26307136
TI  - PpYUC11, a strong candidate gene for the stony hard phenotype in peach (Prunus
      persica L. Batsch), participates in IAA biosynthesis during fruit ripening.
AB  - High concentrations of indole-3-acetic acid (IAA) are required for climacteric
      ethylene biosynthesis to cause fruit softening in melting flesh peaches at the
      late ripening stage. By contrast, the fruits of stony hard peach cultivars do not
      soften and produce little ethylene due to the low IAA concentrations. To
      investigate the regulation of IAA accumulation during peach ripening [the
      transition from stage S3 to stage S4 III (climacteric)], a digital gene
      expression (DGE) analysis was performed. The expression patterns of auxin
      homeostasis-related genes were compared in fruits of the melting flesh peach
      'Goldhoney 3' and the stony hard flesh peach 'Yumyeong' during the ripening
      stage. It is revealed here that a YUCCA flavin mono-oxygenase gene (PpYUC11,
      ppa008176m), a key gene in auxin biosynthesis, displayed an identical
      differential expression profile to the profiles of IAA accumulation and PpACS1
      transcription: the mRNA transcripts increased at the late ripening stage in
      melting flesh peaches but were below the limit of detection in mature fruits of
      stony hard peaches. In addition, the strong association between intron TC
      microsatellite genotypes of PpYUC11 and the flesh texture (normal or stony hard)
      is described in 43 peach varieties, indicating that this locus may be responsible
      for the stony hard phenotype in peach. These findings support the hypothesis that
      PpYUC11 may play an essential role in auxin biosynthesis during peach fruit
      ripening and is a candidate gene for the control of the stony hard phenotype in
      peach.

PMID- 26307135
TI  - Fibroblast growth factor 23: associations with antiretroviral therapy in patients
      co-infected with HIV and hepatitis C.
AB  - OBJECTIVES: Fibroblast growth factor 23 (FGF23) has been associated with
      cardiovascular mortality. We estimate associations between the level of plasma
      FGF23 and exposure to abacavir (ABC) and to other components of antiretroviral
      therapy in patients co-infected with HIV and hepatitis C. METHODS: Both intact
      and c-terminal FGF23 were measured in plasma using commercial assays for a sub
      cohort of 295 patients selected at random from the 1150 patients enrolled in the
      Canadian Co-infection Cohort. The multiplicative effects of antiretroviral drug
      exposures and covariates on median FGF23 were then estimated using a hierarchical
      Bayesian model. RESULTS: The median level of intact FGF23 was independent of
      either past or recent exposure to abacavir, with multiplicative ratios of 1.00
      and 1.07, 95% credible intervals 0.90-1.12 and 0.94-1.23, respectively. Median
      intact FGF23 tended to increase with past use of both nonnucleoside reverse
      transcriptase inhibitors and protease inhibitors, but tended to decrease with
      recent use of either tenofovir, efavirenz or lopinavir. There were no obvious
      associations between the median level of c-terminal FGF23 and individual drugs or
      drug classes. Age, female gender, smoking and the aspartate aminotransferase to
      platelet ratio index were all associated with a higher median c-terminal FGF23
      but not with a higher median intact FGF23. CONCLUSIONS: The level of FGF23 in
      plasma was independent of exposure to ABC. Lower levels of intact FGF23 with
      recent use of tenofovir, efavirenz or lopinavir may reflect their adverse effects
      on bone and vitamin D metabolism relative to other drugs in their respective drug
      classes.

PMID- 26307137
TI  - New isoforms and assembly of glutamine synthetase in the leaf of wheat (Triticum
      aestivum L.).
AB  - Glutamine synthetase (GS; EC 6.3.1.2) plays a crucial role in the assimilation
      and re-assimilation of ammonia derived from a wide variety of metabolic processes
      during plant growth and development. Here, three developmentally regulated
      isoforms of GS holoenzyme in the leaf of wheat (Triticum aestivum L.) seedlings
      are described using native-PAGE with a transferase activity assay. The isoforms
      showed different mobilities in gels, with GSII>GSIII>GSI. The cytosolic GSI was
      composed of three subunits, GS1, GSr1, and GSr2, with the same molecular weight
      (39.2kDa), but different pI values. GSI appeared at leaf emergence and was active
      throughout the leaf lifespan. GSII and GSIII, both located in the chloroplast,
      were each composed of a single 42.1kDa subunit with different pI values. GSII was
      active mainly in green leaves, while GSIII showed brief but higher activity in
      green leaves grown under field conditions. LC-MS/MS experiments revealed that
      GSII and GSIII have the same amino acid sequence, but GSII has more modification
      sites. With a modified blue native electrophoresis (BNE) technique and in-gel
      catalytic activity analysis, only two GS isoforms were observed: one cytosolic
      and one chloroplastic. Mass calibrations on BNE gels showed that the cytosolic
      GS1 holoenzyme was ~490kDa and likely a dodecamer, and the chloroplastic GS2
      holoenzyme was ~240kDa and likely a hexamer. Our experimental data suggest that
      the activity of GS isoforms in wheat is regulated by subcellular localization,
      assembly, and modification to achieve their roles during plant development. 

PMID- 26307139
TI  - Vascularized posterior interosseous pedicled bone grafting for infected forearm
      nonunion.
AB  - Infected forearm nonunion is challenging to treat. We have used a vascularized
      pedicled bone graft from the distal ulna based on the posterior interosseous
      artery to treat forearm nonunion with current or previous signs of infection in
      six patients. Bone union was achieved after a mean of 3.8 months. After a mean
      follow-up of 25.7 months, no signs of persistent or reactivation of infection
      were seen in any patient. The mean Quick DASH score significantly improved from
      77.4 to 17.6. In addition, the active range of motion of the wrist improved
      significantly after surgery. In our patients, a vascularized posterior
      interosseous pedicled bone from the distal ulna is a reliable vascularized bone
      graft for managing infected forearm nonunion.

PMID- 26307138
TI  - Immune-tolerant elastin-like polypeptides (iTEPs) and their application as CTL
      vaccine carriers.
AB  - BACKGROUND: Cytotoxic T lymphocyte (CTL) vaccine carriers are known to enhance
      the efficacy of vaccines, but a search for more effective carriers is warranted.
      Elastin-like polypeptides (ELPs) have been examined for many medical applications
      but not as CTL vaccine carriers. PURPOSE: We aimed to create immune tolerant ELPs
      using a new polypeptide engineering practice and create CTL vaccine carriers
      using the ELPs. RESULTS: Four sets of novel ELPs, termed immune-tolerant elastin
      like polypeptide (iTEP) were generated according to the principles dictating
      humoral immunogenicity of polypeptides and phase transition property of ELPs. The
      iTEPs were non-immunogenic in mice. Their phase transition feature was confirmed
      through a turbidity assay. An iTEP nanoparticle (NP) was assembled from an
      amphiphilic iTEP copolymer plus a CTL peptide vaccine, SIINFEKL. The NP
      facilitated the presentation of the vaccine by dendritic cells (DCs) and enhanced
      vaccine-induced CTL responses. DISCUSSION: A new ELP design and development
      practice was established. The non-canonical motif and the immune tolerant nature
      of the iTEPs broaden our insights about ELPs. ELPs, for the first time, were
      successfully used as carriers for CTL vaccines. CONCLUSION: It is feasible to
      concurrently engineer both immune-tolerant and functional peptide materials. ELPs
      are a promising type of CTL vaccine carriers.

PMID- 26307140
TI  - New insights into the immediate outcome of collagenase injections for Dupuytren's
      contracture.
AB  - Collagenase clostridium histolyticum is now established as an effective and safe
      option to treat patients with a single joint affected with Dupuytren's
      contracture. We have extended its use to natatory and combined cords. In a
      prospective consecutive series of 298 cords in 237 patients, the mean total
      extension loss improved in cords crossing the metacarpophalangeal joint from 46
      degrees  to 1 degrees , in cords crossing the proximal interphalangeal joint from
      56 degrees  to 7 degrees , in natatory cords from 130 degrees  to 25 degrees  and
      in combined cords from 102 degrees  to 16 degrees . The immediate correction of
      combined cords and natatory cords was less reliable than that obtained in cords
      crossing the metacarpophalangeal joint or proximal interphalangeal joint. Less
      severe pre-intervention contractures tended to correct better. We found a high
      complication rate, which may cause alarm. A total of 21% developed skin splits,
      with the risk of skin splits generally increasing with more severe pre-injection
      deformity. Blood blisters were only encountered after manipulation of the more
      severe contractures. A total of 23 patients (8%) had a spontaneous rupture and 57
      patients (19%) had a partial spontaneous rupture. Only 4.9% needed a second
      injection. We noticed a learning curve, with seven of the first 20 cords (35%)
      needing a second injection to achieve a satisfactory correction and then only
      seven (2.5%) in the rest. LEVEL OF EVIDENCE: IV.

PMID- 26307141
TI  - Bony myoepithelioma: a rare condition presenting in the hand.

PMID- 26307143
TI  - Impact of scapholunate dissociation on human wrist kinematics.
AB  - Neither the complex motions of the scapholunate joint, nor the kinematic changes
      that occur as a result of injury to it, are fully understood. We used
      electromagnetic tracking within affected bones to evaluate the physiologic
      motions in the planes of flexion and extension, and of radial and ulnar deviation
      of human cadaver wrists, before and after complete transection of the
      scapholunate ligaments. Despite individual variance between each wrist, we were
      able to establish a pattern in the changes that occurred after scapholunate
      ligament injury. During the motions examined, the scaphoid showed an increase in
      translational deviation in almost all motion axes. In contrast, the movement of
      the lunate seemed to be impaired, especially in radial-ulnar deviation.

PMID- 26307142
TI  - Validity of the Disabilities of the Arm, Shoulder and Hand patient-reported
      outcome measure (DASH) and the Quickdash when used in Dupuytren's disease.
AB  - This study investigated aspects of the validity and reliability of the 30-item
      Disabilities of the Arm, Shoulder and Hand patient-reported outcome measure
      (DASH) and its relationship with the shorter 11-item QuickDASH in patients with
      Dupuytren's disease.Seven hundred and fifty-nine DASH questionnaires were
      studied, covering pre- and postoperative patients undergoing different treatments
      for Dupuytren's disease. Items related to pain rose early after treatment before
      returning to baseline, suggesting that studying pain is relevant during
      postoperative recovery. Across all 759 sets of responses, the QuickDASH agreed
      closely with the DASH. In exploratory factor analysis, the DASH was not
      unidimensional, questioning the validity of the DASH summary score in Dupuytren's
      disease.Further validation of existing PROMs for use in Dupuytren's disease is
      needed. These data suggest that pain is a relevant symptom to study during
      postoperative recovery following treatment for Dupuytren's disease. LEVEL OF
      EVIDENCE: III.

PMID- 26307144
TI  - Correlates of Mental Depression Among Female Sex Workers in Southern India.
AB  - Mental health is an integral part of overall health status but has been a largely
      neglected issue in the developing world especially among female sex workers
      (FSWs). This study examines the prevalence and correlates of major depression
      among FSWs in southern India. Major depression was assessed using Patient Health
      Questionnaire-2 depression scale data from a cross-sectional Behavioral Tracking
      Survey, 2010-2011 conducted among FSWs (n = 1986) in Andhra Pradesh, a state in
      southern India. Almost two-fifths of FSWs (39%) reported major depression.
      Multivariate logistic regression analysis shows a significant association between
      major depression and the following characteristics for FSWs: low autonomy,
      alcohol use, experience of violence, police arrest, inconsistent condom use with
      clients, mobility for sex work, and being HIV positive or not wanting to disclose
      HIV status. Research and advocacy efforts are needed to ensure that the mental
      health issues of marginalized groups are appropriately addressed in HIV
      prevention programs. 

PMID- 26307145
TI  - Lifestyle Behaviors Predict Negative and Positive Changes in Self-reported
      Health: The Role of Immigration to the United States for Koreans.
AB  - Studies of changes in health following immigration are inconsistent, and few are
      based on longitudinal designs to test associations based on change. This study
      identified factors that predicted changes in self-reported health (SRH) among
      California residents of Korean descent. A sample of California residents of
      Korean descent were interviewed and followed-up 2 or 3 times by telephone during
      2001-2009. The questionnaires dealt with SRH, lifestyle behaviors (smoking,
      physical activity, and fast food consumption), and socioeconomic measures.
      Statistical analysis included random-intercepts longitudinal regression models
      predicting change in SRH. A similar percentage of respondents reported improved
      and deteriorating SRH (30.3% and 29.1%, respectively). Smoking, consumption of
      fast foods, age, percentage of life spent in the United States, and being female
      were predictors of deteriorating SRH, whereas physical activity, education, and
      living with a partner were predictive of improvement in SRH. The effect of
      immigration on SRH is influenced by socioeconomic factors and lifestyle
      practices. Results support promotion of healthy lifestyle practices among
      immigrants. 

PMID- 26307146
TI  - Violence Against Children in the Asia Pacific Region: The Situation Is Becoming
      Clearer.

PMID- 26307147
TI  - Quantum dot-imprinted polymers with size and shell-selective recognition
      properties.
AB  - The emergence of nanotechnology has stimulated a great deal of research to detect
      engineered nanoparticles spread out in the environment. We address this issue
      here by designing quantum dot-imprinted polymers for the speciation of
      nanoparticles based on their size, shape and surface chemistry. 

PMID- 26307148
TI  - Controllable high-throughput high-quality femtosecond laser-enhanced chemical
      etching by temporal pulse shaping based on electron density control.
AB  - We developed an efficient fabrication method of high-quality concave microarrays
      on fused silica substrates based on temporal shaping of femtosecond (fs) laser
      pulses. This method involves exposures of fs laser pulse trains followed by a wet
      etching process. Compared with conventional single pulses with the same
      processing parameters, the temporally shaped fs pulses can enhance the etch rate
      by a factor of 37 times with better controllability and higher quality. Moreover,
      we demonstrated the flexibility of the proposed method in tuning the profile of
      the concave microarray structures by changing the laser pulse delay, laser
      fluence, and pulse energy distribution ratio. Micro-Raman spectroscopy was
      conducted to elucidate the stronger modification induced by the fs laser pulse
      trains in comparison with the single pulses. Our calculations show that the
      controllability is due to the effective control of localized transient free
      electron densities by temporally shaping the fs pulses. 

PMID- 26307149
TI  - Kcne2 deletion promotes atherosclerosis and diet-dependent sudden death.
AB  - Coronary artery disease (CAD) is the leading cause of death worldwide. An
      estimated half of cases involve genetic predisposition. Sequence variants in
      human KCNE2, which encodes a cardiac and epithelial K(+) channel beta subunit,
      cause inherited cardiac arrhythmias. Unexpectedly, human KCNE2 polymorphisms also
      associate with predisposition to atherosclerosis, with unestablished causality or
      mechanisms. Here, we report that germline Kcne2 deletion promotes atherosclerosis
      in mice, overcoming the relative resistance of this species to plaque deposition.
      In female western diet-fed mice, Kcne2 deletion increased plaque deposition >6
      fold and also caused premature ventricular complexes and sudden death. The data
      establish causality for the first example of ion channel-linked atherosclerosis,
      and demonstrate that the severity of Kcne2-linked cardiac arrhythmias is strongly
      diet-dependent. 

PMID- 26307150
TI  - Unopposed Estrogen Supplementation/Progesterone Deficiency in Post-Reproductive
      Age Affects the Secretory Profile of Resident Macrophages in a Tissue-Specific
      Manner in the Rat.
AB  - PROBLEM: The influence of unopposed estrogen replacement/isolated progesterone
      deficiency on macrophage production of pro-inflammatory/anti-inflammatory
      mediators in the post-reproductive age was studied. METHOD OF STUDY: Considering
      that in the rats post-ovariectomy the circulating estradiol, but not progesterone
      level rises to the values in sham-operated controls, 20-month-old rats
      ovariectomized at the age of 10 months served as an experimental model. Estrogen
      and progesterone receptor expression, secretion of pro- and anti-inflammatory
      cytokines, and arginine metabolism end-products were examined in splenic and
      peritoneal macrophages under basal conditions and following lipopolysaccharide
      (LPS) stimulation in vitro. RESULTS: Almost all peritoneal and a subset of
      splenic macrophages expressed the intracellular progesterone receptor.
      Ovariectomy diminished cytokine production by splenic (IL-1beta) and peritoneal
      (TNF-alpha, IL-1beta, IL-10) macrophages and increased the production of IL-10 by
      splenic and TGF-beta by peritoneal cells under basal conditions. Following LPS
      stimulation, splenic macrophages from ovariectomized rats produced less TNF-alpha
      and more IL-10, whereas peritoneal macrophages produced less IL-1beta and TGF
      beta than the corresponding cells from sham-operated rats. Ovariectomy diminished
      urea production in both subpopulations of LPS-stimulated macrophages. CONCLUSION:
      Although long-lasting isolated progesterone deficiency in the post-reproductive
      age differentially affects cytokine production in the macrophages from distinct
      tissue compartments, in both subpopulations, it impairs the pro-inflammatory/anti
      inflammatory cytokine secretory balance.

PMID- 26307151
TI  - Real-time analysis of conformational control in electron transfer reactions of
      human cytochrome P450 reductase with cytochrome c.
AB  - Protein domain dynamics and electron transfer chemistry are often associated, but
      real-time analysis of domain motion in enzyme-catalysed reactions and the
      elucidation of mechanistic schemes that relate these motions to the reaction
      chemistry are major challenges for biological catalysis research. Previously we
      suggested that reduction of human cytochrome P450 reductase with the reducing
      coenzyme NADPH is accompanied by major structural re-orientation of the FMN- and
      FAD-binding domains through an inferred dynamic cycle of 'open' and 'closed'
      conformations of the enzyme (PLoS Biol, 2011, e1001222). However, these studies
      were restricted to stopped-flow/FRET analysis of the reductive half-reaction, and
      were compromised by fluorescence quenching of the acceptor by the flavin
      cofactors. Here we have improved the design of the FRET system, by using dye
      pairs with near-IR fluorescence, and extended studies on human cytochrome P450
      reductase to the oxidative half-reaction using a double-mixing stopped-flow
      assay, thereby analysing in real-time conformational dynamics throughout the
      complete catalytic cycle. We correlate redox changes accompanying the reaction
      chemistry with protein dynamic changes observed by FRET, and show that redox
      chemistry drives a major re-orientation of the protein domains in both the
      reductive and oxidative half-reactions. Our studies using the tractable (soluble)
      surrogate electron acceptor cytochrome c provide a framework for analysing
      mechanisms of electron transfer in the endoplasmic reticulum between cytochrome
      P450 reductase and cognate P450 enzymes. More generally, our work emphasizes the
      importance of protein dynamics in intra- and inter-protein electron transfer, and
      establishes methodology for real-time analysis of structural changes throughout
      the catalytic cycle of complex redox proteins.

PMID- 26307152
TI  - Intermediate addition multifocals provide safe stair ambulation with adequate
      'short-term' reading.
AB  - PURPOSE: A recent randomised controlled trial indicated that providing long-term
      multifocal wearers with a pair of distance single-vision spectacles for use
      outside the home reduced falls risk in active older people. However, it also
      found that participants disliked continually switching between using two pairs of
      glasses and adherence to the intervention was poor. In this study we determined
      whether intermediate addition multifocals (which could be worn most of the time
      inside and outside the home and thus avoid continual switching) could provide
      similar gait safety on stairs to distance single vision spectacles whilst also
      providing adequate 'short-term' reading and near vision. METHODS: Fourteen
      healthy long-term multifocal wearers completed stair ascent and descent trials
      over a 3-step staircase wearing intermediate and full addition bifocals and
      progression-addition lenses (PALs) and single-vision distance spectacles. Gait
      safety/caution was assessed using foot clearance measurements (toe on ascent,
      heel on descent) over the step edges and ascent and descent duration. Binocular
      near visual acuity, critical print size and reading speed were measured using
      Bailey-Lovie near charts and MNRead charts at 40 cm. RESULTS: Gait safety/caution
      measures were worse with full addition bifocals and PALs compared to intermediate
      bifocals and PALs. The intermediate PALs provided similar gait ascent/descent
      measures to those with distance single-vision spectacles. The intermediate
      addition PALs also provided good reading ability: Near word acuity and MNRead
      critical print size were better with the intermediate addition PALs than with the
      single-vision lenses (p < 0.0001), with a mean near visual acuity of 0.24 +/-
      0.13 logMAR (~N5.5) which is satisfactory for most near vision tasks when
      performed for a short period of time. CONCLUSIONS: The better ability to 'spot
      read' with the intermediate addition PALs compared to single-vision spectacles
      suggests that elderly individuals might better comply with the use of
      intermediate addition PALs outside the home. A lack of difference in gait
      parameters for the intermediate addition PALs compared to distance single-vision
      spectacles suggests they could be usefully used to help prevent falls in older
      well-adapted full addition PAL wearers. A randomised controlled trial to
      investigate the usefulness of intermediate multifocals in preventing falls seems
      warranted.

PMID- 26307153
TI  - External versus internal fixation for bicondylar tibial plateau fractures:
      systematic review and meta-analysis.
AB  - BACKGROUND: It is uncertain whether external fixation or open reduction internal
      fixation (ORIF) is optimal for patients with bicondylar tibial plateau fractures.
      MATERIALS AND METHODS: A systematic review using Ovid MEDLINE, Embase Classic,
      Embase, AMED, the Cochrane Library, Open Grey, Orthopaedic Proceedings, WHO
      International Clinical Trials Registry Platform, Current Controlled Trials, US
      National Institute for Health Trials Registry, and the Cochrane Central Register
      of Controlled Trials. The search was conducted on 3rd October 2014 and no
      language limits were applied. Inclusion criteria were all clinical study designs
      comparing external fixation with open reduction internal fixation of bicondylar
      tibial plateau fractures. Studies of only one treatment modality were excluded,
      as were those that included unicondylar tibial plateau fractures. Treatment
      effects from studies reporting dichotomous outcomes were summarised using odds
      ratios. Continuous outcomes were converted to standardized mean differences to
      assess the treatment effect, and inverse variance methods used to combine data. A
      fixed effect model was used for meta-analyses. RESULTS: Patients undergoing
      external fixation were more likely to have returned to preinjury activities by
      six and twelve months (P = 0.030) but not at 24 months follow-up. However,
      external fixation was complicated by a greater number of infections (OR 2.59, 95
      % CI 1.25-5.36, P = 0.01). There were no statistically significant differences in
      the rates of deep infection, venous thromboembolism, compartment syndrome, or
      need for re-operation between the two groups. CONCLUSION: Although external
      fixation and ORIF are associated with different complication profiles, both are
      acceptable strategies for managing bicondylar tibial plateau fractures.

PMID- 26307154
TI  - The role of internal forward models and proprioception in hand position
      estimation.
AB  - Our ability to properly move and react in different situations is largely
      dependent on our perception of our limbs' position. At least three sources -
      vision, proprioception, and internal forward models (FMs) - seem to contribute to
      this perception. To the best of our knowledge, the effect of each source has not
      been studied individually. Specifically, role of FM has been ignored in some
      previous studies. We hypothesized that FM has a critical role in subjects'
      perception which needs to be considered in the relevant studies to obtain more
      reliable results. Therefore, we designed an experiment with the goal of
      investigating FM and proprioception role in subjects' perception of their hand's
      position. Three groups of subjects were recruited in the study. Based on the
      experiment design, it was supposed that subjects in different groups relied on
      proprioception, FM, and both of them for estimating their unseen hand's position.
      Comparing the results of three groups revealed significant difference between
      their estimation' errors. FM provided minimum estimation error, while
      proprioception had a bias error in the tested region. Integrating proprioception
      with FM decreased this error. Integration of two Gaussian functions, fitted to
      the error distribution of FM and proprioception groups, was simulated and created
      a mean error value almost similar to the experimental observation. These results
      suggest that FM role needs to be considered when studying the perceived position
      of the limbs. This can lead to gain better insights into the mechanisms
      underlying the perception of our limbs' position which might have potential
      clinical and rehabilitation applications, e.g., in the postural control of
      elderly which are at high risk of falls and injury because of deterioration of
      their perception with age. 

PMID- 26307155
TI  - Varicella-Zoster Immunity in US Healthcare Personnel With Self-Reported History
      of Disease.

PMID- 26307156
TI  - Metabolic adaptations in the adipose tissue that underlie the body fat mass gain
      in middle-aged rats.
AB  - Little is known about adipocyte metabolism during aging process and whether this
      can influence body fat redistribution and systemic metabolism. To better
      understand this phenomenon, two animal groups were studied: young-14 weeks old
      and middle-aged-16 months old. Periepididymal (PE) and subcutaneous (SC)
      adipocytes were isolated and tested for their capacities to perform lipolysis and
      to incorporate D-[U-(14)C]-glucose, D-[U-(14)C]-lactate, and [9,10(n)-(3)H]-oleic
      acid into lipids. Additionally, the morphometric characteristics of the adipose
      tissues, glucose tolerance tests, and biochemical determinations (fasting
      glucose, triglycerides, insulin) in blood were performed. The middle-aged rats
      showed adipocyte (PE and SC) hypertrophy and glucose intolerance, although there
      were no significant changes in fasting glycemia and insulin. Furthermore, PE
      tissue revealed elevated rates (+50 %) of lipolysis during beta-adrenergic
      stimulation. There was also an increase (+62 %) in the baseline rate of glucose
      incorporation into lipids in the PE adipocytes, while these PE cells were almost
      unresponsive to insulin stimulation and less responsive (a 34 % decrease) in the
      SC tissue. Also, the capacity of oleic acid esterification was elevated in
      baseline state and with insulin stimulus in the PE tissue (+90 and 82 %,
      respectively). Likewise, spontaneous incorporation of lactate into lipids in the
      PE and SC tissues was higher (+100 and 11 %, respectively) in middle-aged rats.
      We concluded that adipocyte metabolism of middle-aged animals seems to strongly
      favor cellular hypertrophy and increased adipose mass, particularly the intra
      abdominal PE fat pad. In discussion, we have interpreted all these results as a
      metabolic adaptations to avoid the spreading of fat that can reach tissues beyond
      adipose protecting them against ectopic fat accumulation. However, these
      adaptations may have the potential to lead to future metabolic dysfunctions seen
      in the senescence.

PMID- 26307157
TI  - [Objective DNA malignancy grading as adjunct to the histological Gleason score:
      Frankfurt consensus].

PMID- 26307158
TI  - A retrospective review of the progress in amyotrophic lateral sclerosis drug
      discovery over the last decade and a look at the latest strategies.
AB  - INTRODUCTION: Drug discovery for amyotrophic lateral sclerosis (ALS) has
      experienced a surge in clinical studies and remarkable preclinical milestones
      utilizing a variety of mutant superoxide dismutase 1 model systems. Of the drugs
      that were tested and showed positive preclinical effects, none demonstrated
      therapeutic benefits to ALS patients in clinical settings. AREAS COVERED: This
      review discusses the advances made in drug discovery for ALS and highlights why
      drug development is proving to be so difficult. It also discusses how a closer
      look at both preclinical and clinical studies could uncover the reasons why these
      preclinical successes have yet to result in the availability of an effective drug
      for clinical use. EXPERT OPINION: Valuable lessons from the numerous preclinical
      and clinical studies supply the biggest advantage in the monumental task of
      finding a cure for ALS. Obviously, a single design type for ALS clinical trials
      has not yielded success. The authors suggest a two-pronged approach that may
      prove essential to achieve clinical efficacy in the identification of novel
      targets and preclinical testing in multiple models to identify biomarkers that
      can function in diagnostic, predictive and prognostic roles, and changes to
      clinical trial design and patient recruitment criteria. The advancement of
      technology and invention of more powerful tools will further enhance the above.
      This will give rise to more sophisticated clinical trials with consideration of a
      range of criteria from: optimum dose, route of delivery, specific biomarkers,
      pharmacokinetics, pharmacodynamics and toxicology to biomarkers, timing for trial
      and patients' clinical status.

PMID- 26307159
TI  - Patient reported adherence to hypertension treatment: A revalidation study.
AB  - BACKGROUND: Adherence to hypertension management in patients with hypertension is
      known to influence their blood pressure control. It is important to measure
      patients' adherence behaviours to assist with designing appropriate interventions
      to improve blood pressure control. AIMS: The purposes of this study were to use
      confirmatory factor analysis to revalidate the Therapeutic Adherence Scale for
      Hypertensive Patients (TASHP), and to calculate the cut-off score for classifying
      adherence behaviours into two groups: satisfactory and low adherence behaviours.
      METHODS: Systematic random sampling was used to recruit patients with
      hypertension in China. Demographic characteristics, the TASHP and blood pressure
      were collected. The psychometric tests of the TASHP included: construct validity,
      criteria-related validity, internal reliability, and split-half reliability. The
      area under the receiver operating characteristics curve and Youden index were
      used to identify the cut-off score of the TASHP for blood pressure control.
      RESULTS: This study involved 366 patients. Confirmatory factor analysis supported
      the four-component structure of the TASHP proposed in the original scale
      development study. The TASHP has a satisfactory internal reliability (Cronbach's
      alpha > 0.7) and a satisfactory split-half reliability (Spearman-Brown
      coefficients > 0.7). The patients with overall scores of the TASHP ? 109 points
      were considered to have satisfactory adherence behaviours. CONCLUSION: The TASHP
      is a validated and reliable instrument to measure the adherence to hypertension
      management in Chinese patients with hypertension. The cut-off score of 109 points
      can be considered as an effective measure to classify the level of adherence into
      satisfactory and low adherence behaviours.

PMID- 26307160
TI  - Do Ultrasensitive Prostate Specific Antigen Measurements Have a Role in
      Predicting Long-Term Biochemical Recurrence-Free Survival in Men after Radical
      Prostatectomy?
AB  - PURPOSE: In this study we evaluate an ultrasensitive prostate specific antigen
      assay in patients with prostate cancer after radical prostatectomy to predict
      long-term biochemical recurrence-free survival. MATERIALS AND METHODS: A total of
      754 men who underwent radical prostatectomy and had an undetectable prostate
      specific antigen after surgery (less than 0.1 ng/ml) were studied. Prostate
      specific antigen was measured in banked serum specimens with an ultrasensitive
      assay (Hybritech(r) PSA, Beckman Coulter Access(r) 2) using a cutoff of 0.01
      ng/ml. Prostate specific antigen was also measured in 44 men after
      cystoprostatectomy who had no pathological evidence of prostate cancer with the
      Hybritech assay and with the Quanterix AccuPSATM assay. RESULTS: Of the 754 men
      17% (131) experienced biochemical recurrence (median 4.0 years). Those men
      without biochemical recurrence (83%, 623) had a minimum of 5 years of followup
      (median 11). Prostate specific antigen was less than 0.01 ng/ml in 93.4% of men
      with no biochemical recurrence, whereas 30.5% of men with biochemical recurrence
      had a prostate specific antigen of 0.01 ng/ml or greater. On multivariate
      analysis postoperative prostate specific antigen at a 0.01 ng/ml cutoff,
      pathological stage and Gleason score, and surgical margins were significant
      independent predictors of biochemical recurrence risk. Kaplan-Meier estimates for
      mean biochemical recurrence-free survival were 15.2 years (95% CI 14.9-15.6) for
      prostate specific antigen less than 0.01 ng/ml and 10.0 years (95% CI 8.4-11.5)
      for prostate specific antigen 0.01 ng/ml or greater (p <0.0001). Biochemical
      recurrence-free rates 11 years after surgery were 86.1% (95% CI 83.2-89.0) for
      prostate specific antigen less than 0.01 ng/ml and 48.9% (95% CI 37.5-60.3) for
      prostate specific antigen 0.01 ng/ml or greater (p <0.0001). Prostate specific
      antigen concentrations in 44 men after cystoprostatectomy were all less than 0.03
      ng/ml, with 95.4% less than 0.01 ng/ml. CONCLUSIONS: In men with a serum prostate
      specific antigen less than 0.1 ng/ml after radical prostatectomy a tenfold lower
      cutoff (0.01 ng/ml) stratified biochemical recurrence-free survival and was a
      significant independent predictor of biochemical recurrence, as were pathological
      features. Prostate specific antigen concentrations in men without pathological
      evidence of prostate cancer suggest that a higher prostate specific antigen
      concentration (0.03 ng/ml) in the ultrasensitive range may be needed to define
      the detection threshold.

PMID- 26307161
TI  - A Feasibility Study to Determine Whether Clinical Contrast Enhanced Magnetic
      Resonance Imaging can Detect Increased Bladder Permeability in Patients with
      Interstitial Cystitis.
AB  - PURPOSE: Interstitial cystitis/bladder pain syndrome is a bladder pain disorder
      associated with voiding symptomatology and other systemic chronic pain disorders.
      Currently diagnosing interstitial cystitis/bladder pain syndrome is complicated
      as patients present with a wide range of symptoms, physical examination findings
      and clinical test responses. One hypothesis is that interstitial cystitis
      symptoms arise from increased bladder permeability to urine solutes. This study
      establishes the feasibility of using contrast enhanced magnetic resonance imaging
      to quantify bladder permeability in patients with interstitial cystitis.
      MATERIALS AND METHODS: Permeability alterations in bladder urothelium were
      assessed by intravesical administration of the magnetic resonance imaging
      contrast agent Gd-DTPA (Gd-diethylenetriaminepentaacetic acid) in a small cohort
      of patients. Magnetic resonance imaging signal intensity in patient and control
      bladders was compared regionally and for entire bladders. RESULTS: Quantitative
      assessment of magnetic resonance imaging signal intensity indicated a significant
      increase in signal intensity in anterior bladder regions compared to posterior
      regions in patients with interstitial cystitis (p <0.01) and significant
      increases in signal intensity in anterior bladder regions (p <0.001). Kurtosis
      (shape of probability distribution) and skewness (measure of probability
      distribution asymmetry) were associated with contrast enhancement in total
      bladders in patients with interstitial cystitis vs controls (p <0.05). Regarding
      symptomatology interstitial cystitis cases differed significantly from controls
      on the SF-36(r), PUF (Pelvic Pain and Urgency/Frequency) and ICPI (Interstitial
      Cystitis Problem Index) questionnaires with no overlap in the score range in each
      group. ICSI (Interstitial Cystitis Symptom Index) differed significantly but with
      a slight overlap in the range of scores. CONCLUSIONS: Data suggest that contrast
      enhanced magnetic resonance imaging provides an objective, quantifiable
      measurement of bladder permeability that could be used to stratify bladder pain
      patients and monitor therapy.

PMID- 26307162
TI  - Randomized Controlled Study of the Efficacy, Safety and Quality of Life with Low
      Dose bacillus Calmette-Guerin Instillation Therapy for Nonmuscle Invasive Bladder
      Cancer.
AB  - PURPOSE: The optimal dose of intravesical bacillus Calmette-Guerin for the
      treatment of nonmuscle invasive bladder cancer is controversial. We investigated
      if induction therapy with low dose bacillus Calmette-Guerin could achieve a
      complete response rate similar to that of standard dose bacillus Calmette-Guerin,
      with less toxicity and higher quality of life. MATERIALS AND METHODS: After
      transurethral resection, patients with unresectable multiple nonmuscle invasive
      bladder cancer and/or carcinoma in situ were randomized to receive standard (80
      mg) or low dose (40 mg) bacillus Calmette-Guerin instillation induction therapy
      (weekly, 8 times). The primary end point was noninferiority of low dose bacillus
      Calmette-Guerin with a null hypothesis of a 15% decrease in complete response
      rate. Secondary end points were recurrence-free survival, progression-free
      survival, overall survival, patient compliance, adverse events and quality of
      life using the EORTC QLQ-C30. RESULTS: In an intent to treat analysis of 166
      patients the complete response rates for low dose and standard dose bacillus
      Calmette-Guerin were 79% (95% CI 0.70-0.88) and 85% (95% CI 0.77-0.92),
      respectively. Dunnett-Gent analysis revealed that the null hypothesis of
      inferiority of low dose bacillus Calmette-Guerin in terms of complete response
      could not be rejected (p = 0.119). However, there were no significant differences
      between the groups in terms of recurrence, progression and overall survival. Low
      dose bacillus Calmette-Guerin was associated with significantly less fever (p =
      0.001) and micturition pain (p = 0.047), and significantly higher quality of life
      scores for global quality of life, role functioning and functional impairment.
      CONCLUSIONS: The noninferiority of low dose bacillus Calmette-Guerin was not
      proven. However, low dose bacillus Calmette-Guerin was associated with lower
      toxicity and higher quality of life compared to standard dose bacillus Calmette
      Guerin in patients with nonmuscle invasive bladder cancer.

PMID- 26307163
TI  - Wolf Piranha Versus Lumenis VersaCut Prostate Morcellation Devices: A Prospective
      Randomized Trial.
AB  - PURPOSE: Holmium laser enucleation of the prostate for the management of benign
      prostatic hyperplasia involves the 2 steps of enucleation and morcellation. Few
      prostate morcellation devices are available. In this study we compare the Wolf
      Piranha and Lumenis(r) VersaCutTM prostate morcellation devices. MATERIALS AND
      METHODS: After institutional review board approval and patient informed consent,
      a prospective, randomized trial was initiated for patients with symptomatic
      benign prostatic hyperplasia undergoing holmium laser enucleation of the
      prostate. All procedures were performed by a single surgeon (JEL) at Indiana
      University Health Methodist Hospital using the Piranha or VersaCut prostate
      morcellation device. Patient demographics, and preoperative, intraoperative and
      postoperative data for patients in the 2 treatment groups were analyzed and
      compared in a prospective fashion. RESULTS: A total of 74 patients were enrolled
      and randomized for the treatment device. Both groups were comparable in terms of
      age, prostate specific antigen and prostate size. There was no difference in
      patient demographic and preoperative characteristics. The Piranha achieved a
      slightly higher morcellation rate at 5.6 gm per minute (range 1.4 to 18),
      compared to the VersaCut at 4.8 gm per minute (range 1.3 to 9.5). However, the
      difference was not statistically significant (p = 0.14). Cost analysis (USD per
      patient) favored the VersaCut ($241 vs $471, p <0.001). CONCLUSIONS: Morcellation
      rates for the Piranha and VersaCut prostate morcellation devices are comparable,
      with the Piranha having a statistically significant increased cost. The Wolf
      Piranha also has a more complicated design, making it less user-friendly for the
      operating room staff and, therefore, more difficult to troubleshoot than the
      Lumenis VersaCut. Nevertheless, 75% of urology faculty, fellows and residents
      preferred the Piranha over the VersaCut, reporting that when working properly, it
      was more efficient in tissue removal.

PMID- 26307164
TI  - Staphylococcus aureus Biofilms Induce Macrophage Dysfunction Through Leukocidin
      AB and Alpha-Toxin.
AB  - The macrophage response to planktonic Staphylococcus aureus involves the
      induction of proinflammatory microbicidal activity. However, S. aureus biofilms
      can interfere with these responses in part by polarizing macrophages toward an
      anti-inflammatory profibrotic phenotype. Here we demonstrate that conditioned
      medium from mature S. aureus biofilms inhibited macrophage phagocytosis and
      induced cytotoxicity, suggesting the involvement of a secreted factor(s).
      Iterative testing found the active factor(s) to be proteinaceous and partially
      agr-dependent. Quantitative mass spectrometry identified alpha-toxin (Hla) and
      leukocidin AB (LukAB) as critical molecules secreted by S. aureus biofilms that
      inhibit murine macrophage phagocytosis and promote cytotoxicity. A role for Hla
      and LukAB was confirmed by using hla and lukAB mutants, and synergy between the
      two toxins was demonstrated with a lukAB hla double mutant and verified by
      complementation. Independent confirmation of the effects of Hla and LukAB on
      macrophage dysfunction was demonstrated by using an isogenic strain in which Hla
      was constitutively expressed, an Hla antibody to block toxin activity, and
      purified LukAB peptide. The importance of Hla and LukAB during S. aureus biofilm
      formation in vivo was assessed by using a murine orthopedic implant biofilm
      infection model in which the lukAB hla double mutant displayed significantly
      lower bacterial burdens and more macrophage infiltrates than each single mutant.
      Collectively, these findings reveal a critical synergistic role for Hla and LukAB
      in promoting macrophage dysfunction and facilitating S. aureus biofilm
      development in vivo. IMPORTANCE: Staphylococcus aureus has a propensity to form
      multicellular communities known as biofilms. While growing in a biofilm, S.
      aureus displays increased tolerance to nutrient deprivation, antibiotic insult,
      and even host immune challenge. Previous studies have shown that S. aureus
      biofilms thwart host immunity in part by preventing macrophage phagocytosis. It
      remained unclear whether this was influenced solely by the considerable size of
      biofilms or whether molecules were also actively secreted to circumvent
      macrophage-mediated phagocytosis. This is the first report to demonstrate that S.
      aureus biofilms inhibit macrophage phagocytosis and induce macrophage death
      through the combined action of leukocidin AB and alpha-toxin. Loss of leukocidin
      AB and alpha-toxin expression resulted in enhanced S. aureus biofilm clearance in
      a mouse model of orthopedic implant infection, suggesting that these toxins could
      be targeted therapeutically to facilitate biofilm clearance in humans.

PMID- 26307165
TI  - Pseudomonas aeruginosa Expresses a Functional Human Natriuretic Peptide Receptor
      Ortholog: Involvement in Biofilm Formation.
AB  - Considerable evidence exists that bacteria detect eukaryotic communication
      molecules and modify their virulence accordingly. In previous studies, it has
      been demonstrated that the increasingly antibiotic-resistant pathogen Pseudomonas
      aeruginosa can detect the human hormones brain natriuretic peptide (BNP) and C
      type natriuretic peptide (CNP) at micromolar concentrations. In response, the
      bacterium modifies its behavior to adapt to the host physiology, increasing its
      overall virulence. The possibility of identifying the bacterial sensor for these
      hormones and interfering with this sensing mechanism offers an exciting
      opportunity to directly affect the infection process. Here, we show that BNP and
      CNP strongly decrease P. aeruginosa biofilm formation. Isatin, an antagonist of
      human natriuretic peptide receptors (NPR), prevents this effect. Furthermore, the
      human NPR-C receptor agonist cANF(4-23) mimics the effects of natriuretic
      peptides on P. aeruginosa, while sANP, the NPR-A receptor agonist, appears to be
      weakly active. We show in silico that NPR-C, a preferential CNP receptor, and the
      P. aeruginosa protein AmiC have similar three-dimensional (3D) structures and
      that both CNP and isatin bind to AmiC. We demonstrate that CNP acts as an AmiC
      agonist, enhancing the expression of the ami operon in P. aeruginosa. Binding of
      CNP and NPR-C agonists to AmiC was confirmed by microscale thermophoresis.
      Finally, using an amiC mutant strain, we demonstrated that AmiC is essential for
      CNP effects on biofilm formation. In conclusion, the AmiC bacterial sensor
      possesses structural and pharmacological profiles similar to those of the human
      NPR-C receptor and appears to be a bacterial receptor for human hormones that
      enables P. aeruginosa to modulate biofilm expression. IMPORTANCE: The bacterium
      Pseudomonas aeruginosa is a highly dangerous opportunist pathogen for
      immunocompromised hosts, especially cystic fibrosis patients. The sites of P.
      aeruginosa infection are varied, with predominance in the human lung, in which
      bacteria are in contact with host molecular messengers such as hormones. The C
      type natriuretic peptide (CNP), a hormone produced by lung cells, has been
      described as a bacterial virulence enhancer. In this study, we showed that the
      CNP hormone counteracts P. aeruginosa biofilm formation and we identified the
      bacterial protein AmiC as the sensor involved in the CNP effects. We showed that
      AmiC could bind specifically CNP. These results show for the first time that a
      human hormone could be sensed by bacteria through a specific protein, which is an
      ortholog of the human receptor NPR-C. The bacterium would be able to modify its
      lifestyle by favoring virulence factor production while reducing biofilm
      formation.

PMID- 26307166
TI  - Discovery of a Novel Hepatovirus (Phopivirus of Seals) Related to Human Hepatitis
      A Virus.
AB  - Describing the viral diversity of wildlife can provide interesting and useful
      insights into the natural history of established human pathogens. In this study,
      we describe a previously unknown picornavirus in harbor seals (tentatively named
      phopivirus) that is related to human hepatitis A virus (HAV). We show that
      phopivirus shares several genetic and phenotypic characteristics with HAV,
      including phylogenetic relatedness across the genome, a specific and seemingly
      quiescent tropism for hepatocytes, structural conservation in a key functional
      region of the type III internal ribosomal entry site (IRES), and a codon usage
      bias consistent with that of HAV. IMPORTANCE: Hepatitis A virus (HAV) is an
      important viral hepatitis in humans because of the substantial number of cases
      each year in regions with low socioeconomic status. The origin of HAV is unknown,
      and no nonprimate HAV-like viruses have been described. Here, we describe the
      discovery of an HAV-like virus in seals. This finding suggests that the diversity
      and evolutionary history of these viruses might be far greater than previously
      thought and may provide insight into the origin and pathogenicity of HAV.

PMID- 26307167
TI  - Unconventional N-Linked Glycosylation Promotes Trimeric Autotransporter Function
      in Kingella kingae and Aggregatibacter aphrophilus.
AB  - Glycosylation is a widespread mechanism employed by both eukaryotes and bacteria
      to increase the functional diversity of their proteomes. The nontypeable
      Haemophilus influenzae glycosyltransferase HMW1C mediates unconventional N-linked
      glycosylation of the adhesive protein HMW1, which is encoded in a two-partner
      secretion system gene cluster that also encodes HMW1C. In this system, HMW1 is
      modified in the cytoplasm by sequential transfer of hexose residues. In the
      present study, we examined Kingella kingae and Aggregatibacter aphrophilus
      homologues of HMW1C that are not encoded near a gene encoding an obvious acceptor
      protein. We found both homologues to be functional glycosyltransferases and
      identified their substrates as the K. kingae Knh and the A. aphrophilus EmaA
      trimeric autotransporter proteins. Liquid chromatography-tandem mass spectrometry
      (LC-MS/MS) analysis revealed multiple sites of N-linked glycosylation on Knh and
      EmaA. Without glycosylation, Knh and EmaA failed to facilitate wild-type levels
      of bacterial autoaggregation or adherence to human epithelial cells, establishing
      that glycosylation is essential for proper protein function. IMPORTANCE: This
      work emphasizes the importance of glycosylation for proper function of bacterial
      proteins. Here we show that the Kingella kingae Knh and the Aggregatibacter
      aphrophilus EmaA trimeric autotransporter proteins are N-glycosylated by novel
      homologues of the Haemophilus influenzae HMW1C glycosyltransferase, highlighting
      the first examples of trimeric autotransporters that are modified by HMW1C-like
      enzymes. In the absence of glycosylation, Knh and EmaA lack adhesive activity.
      This work has relevance to our understanding of bacterial pathogenicity and
      expression of potential vaccine antigens.

PMID- 26307168
TI  - A New Noncoding RNA Arranges Bacterial Chromosome Organization.
AB  - Repeated extragenic palindromes (REPs) in the enterobacterial genomes are usually
      composed of individual palindromic units separated by linker sequences. A total
      of 355 annotated REPs are distributed along the Escherichia coli genome. RNA
      sequence (RNAseq) analysis showed that almost 80% of the REPs in E. coli are
      transcribed. The DNA sequence of REP325 showed that it is a cluster of six
      repeats, each with two palindromic units capable of forming cruciform structures
      in supercoiled DNA. Here, we report that components of the REP325 element and at
      least one of its RNA products play a role in bacterial nucleoid DNA condensation.
      These RNA not only are present in the purified nucleoid but bind to the bacterial
      nucleoid-associated HU protein as revealed by RNA IP followed by microarray
      analysis (RIP-Chip) assays. Deletion of REP325 resulted in a dramatic increase of
      the nucleoid size as observed using transmission electron microscopy (TEM), and
      expression of one of the REP325 RNAs, nucleoid-associated noncoding RNA 4
      (naRNA4), from a plasmid restored the wild-type condensed structure.
      Independently, chromosome conformation capture (3C) analysis demonstrated
      physical connections among various REP elements around the chromosome. These
      connections are dependent in some way upon the presence of HU and the REP325
      element; deletion of HU genes and/or the REP325 element removed the connections.
      Finally, naRNA4 together with HU condensed DNA in vitro by connecting REP325 or
      other DNA sequences that contain cruciform structures in a pairwise manner as
      observed by atomic force microscopy (AFM). On the basis of our results, we
      propose molecular models to explain connections of remote cruciform structures
      mediated by HU and naRNA4. IMPORTANCE: Nucleoid organization in bacteria is being
      studied extensively, and several models have been proposed. However, the
      molecular nature of the structural organization is not well understood. Here we
      characterized the role of a novel nucleoid-associated noncoding RNA, naRNA4, in
      nucleoid structures both in vivo and in vitro. We propose models to explain how
      naRNA4 together with nucleoid-associated protein HU connects remote DNA elements
      for nucleoid condensation. We present the first evidence of a noncoding RNA
      together with a nucleoid-associated protein directly condensing nucleoid DNA.

PMID- 26307170
TI  - A Supramolecular Antibiotic Switch for Antibacterial Regulation.
AB  - A supramolecular antibiotic switch is described that can reversibly "turn-on" and
      "turn-off" its antibacterial activity on demand, providing a proof-of-concept for
      a way to regulate antibacterial activity of biotics. The switch relies on
      supramolecular assembly and disassembly of cationic poly(phenylene vinylene)
      derivative (PPV) with cucurbit[7]uril (CB[7]) to regulate their different
      interactions with bacteria. This simple but efficient strategy does not require
      any chemical modification on the active sites of the antibacterial agent, and
      could also regulate the antibacterial activity of classical antibiotics or
      photosensitizers in photodynamic therapy. This supramolecular antibiotic switch
      may be a successful strategy to fight bacterial infections and decrease the
      emergence of bacterial resistance to antibiotics from a long-term point of view. 

PMID- 26307171
TI  - Operator competence in fetoscopic laser surgery for twin-twin transfusion
      syndrome: validation of a procedure-specific evaluation tool.
AB  - OBJECTIVES: Fetoscopic laser surgery for twin-twin transfusion syndrome is a
      procedure for which no objective tools exist to assess technical skills. To
      ensure that future fetal surgeons reach competence prior to performing the
      procedure unsupervised, we developed a performance assessment tool. The aim of
      this study was to validate this assessment tool for reliability and construct
      validity. METHODS: We made use of a procedure-specific evaluation instrument
      containing all essential steps of the fetoscopic laser procedure, which was
      previously created using Delphi methodology. Eleven experts and 13 novices from
      three fetal medicine centers performed the procedure on the same simulator. Two
      independent observers assessed each surgery using the instrument (maximum score:
      52). Interobserver reliability was assessed using Spearman correlation. We
      compared the performance of novices and experts to assess construct validity.
      RESULTS: The interobserver reliability was high (Rs  = 0.974, P < 0.001).
      Checklist scores for experts and novices were significantly different; the median
      score for novices was 28/52 (54%), whereas that for experts was 47.5/52 (91%) (P
      < 0.001). The procedure time and fetoscopy time were significantly shorter (P <
      0.001) for experts. Residual anastomoses were found in 1/11 (9%) procedures
      performed by experts and in 9/13 (69%) procedures performed by novices (P =
      0.005). Multivariable analysis showed that the checklist score, independent of
      age and gender, predicted competence. CONCLUSIONS: The procedure-specific
      assessment tool for fetoscopic laser surgery shows good interobserver reliability
      and discriminates experts from novices. This instrument may therefore be a useful
      tool in the training curriculum for fetal surgeons. Further intervention studies
      with reassessment before and after training may increase the construct validity
      of the tool. Copyright (c) 2015 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 26307169
TI  - Restoration of Physiologically Responsive Low-Density Lipoprotein Receptor
      Mediated Endocytosis in Genetically Deficient Induced Pluripotent Stem Cells.
AB  - Acquiring sufficient amounts of high-quality cells remains an impediment to cell
      based therapies. Induced pluripotent stem cells (iPSC) may be an unparalleled
      source, but autologous iPSC likely retain deficiencies requiring correction. We
      present a strategy for restoring physiological function in genetically deficient
      iPSC utilizing the low-density lipoprotein receptor (LDLR) deficiency Familial
      Hypercholesterolemia (FH) as our model. FH fibroblasts were reprogrammed into
      iPSC using synthetic modified mRNA. FH-iPSC exhibited pluripotency and
      differentiated toward a hepatic lineage. To restore LDLR endocytosis, FH-iPSC
      were transfected with a 31 kb plasmid (pEHZ-LDLR-LDLR) containing a wild-type
      LDLR (FH-iPSC-LDLR) controlled by 10 kb of upstream genomic DNA as well as
      Epstein-Barr sequences (EBNA1 and oriP) for episomal retention and replication.
      After six months of selective culture, pEHZ-LDLR-LDLR was recovered from FH-iPSC
      LDLR and transfected into Ldlr-deficient CHO-a7 cells, which then exhibited
      feedback-controlled LDLR-mediated endocytosis. To quantify endocytosis, FH-iPSC
      +/- LDLR were differentiated into mesenchymal cells (MC), pretreated with excess
      free sterols, Lovastatin, or ethanol (control), and exposed to DiI-LDL. FH-MC
      LDLR demonstrated a physiological response, with virtually no DiI-LDL
      internalization with excess sterols and an ~2-fold increase in DiI-LDL
      internalization by Lovastatin compared to FH-MC. These findings demonstrate the
      feasibility of functionalizing genetically deficient iPSC using episomal plasmids
      to deliver physiologically responsive transgenes. 

PMID- 26307172
TI  - Complete genome sequence of Lactobacillus helveticus KLDS1.8701, a probiotic
      strain producing bacteriocin.
AB  - This study investigated the functional diversity of Lactobacillus helveticus
      KLDS1.8701 by carrying out a whole-genome sequence analyses of L. helveticus
      KLDS1.8701. L. helveticus KLDS1.8701 strain was isolated from traditional sour
      milk in Sinkiang of China with desirable probiotic properties. Here we report the
      complete genome sequence of this organism and its genetic basis for adhesion,
      exopolysaccharides (EPS) production, acid and bile tolerance, bacteriocin
      production and immune system against bacteriophage. 

PMID- 26307173
TI  - Acinetobacter lwoffii an emerging pathogen in neonatal ICU.
AB  - BACKGROUND: Acinetobacter species are ubiquitous in the environment and are
      important causative agent for nososcomial infection especially in
      immunocompromised patients. Multi drug resistant Acinetobacter lwoffii are
      emerging as a pathogen in neoanatal sepsis. AIMS AND OBJECTIVE: This study was
      aimed to evaluate the clinical and antibiotic profile of Acinetobacter lwoffii.
      MATERIAL AND METHODS: This study was done on blood samples from neonates admitted
      to neonatal intensive care unit during a period of one year from January to
      December 2012, who developed Acinetobacter infection. The diagnosis of isolates
      and antibiotic susceptibility testing was done by both conventional as well as by
      automated system. RESULTS: Out of total 13,133 blood samples received for
      culture, 1418(10.8%) were from NICU. Ninety (6.3%) isolates were found to be
      positive for the growth of Acinetobacter species. Of these isolates 31.11% were
      found to be Acinetobacter lwoffii, 68.9% were Acinetobacter baumannii calcaetius
      complex. Acinetobacter lwoffii isolates were most commonly sensitive to imepenem
      16(57%), cotrimoxazole 9(32%), ciprofloxacin 6(21%) followed by amoxyclavulanic
      acid 2(7%) and cefuroxime 1(3.5%). CONCLUSION: Multi drug resistant Acinetobacter
      lwoffii infection is increasing particularly in premature and very low-birth
      weight neonates. Judicious and timely antibiotic use in NICUs are one of the
      important key in controlling multi-drug resistant Acinetobacter infection and
      improving clinical outcome.

PMID- 26307174
TI  - Syphilis as a Cause of Thoracic Aortic Aneurysm.
AB  - In 2009, we described morphologic findings in 22 patients having resection of an
      ascending aortic aneurysm in the previous 11 years at the Baylor University
      Medical Center, and histologic examination of the aneurysmal wall disclosed
      classic findings of syphilitic aortitis. The major purpose of that extensively
      illustrated report was to describe the characteristic gross features of the
      aneurysm such that syphilitic aortitis might be better recognized at operation
      and appropriate antibiotics administered postoperatively. The aim of the present
      study was to emphasize that syphilis remains a major cause of ascending aortic
      aneurysm. From January 1, 2009, to December 31, 2014, we studied additional 23
      patients who had resection of an ascending aortic aneurysm that again
      histologically had classic features of syphilitic aortitis. All 23 patients were
      found to have syphilitic aortitis grossly and histologically. The aneurysm
      involved the ascending portion of aorta in all 23, the arch portion in 12, and
      the descending thoracic portion in 10. In conclusion, syphilis has far from
      disappeared. It remains a major cause of ascending aortic aneurysm. 

PMID- 26307176
TI  - Stable and compact zwitterionic polydiacetylene micelles with tumor-targeting
      properties.
AB  - Compact polymerized polydiacetylene-micelles with "stealth" zwitterionic surface
      coating were assembled and tested in a murine xenograft model of breast cancer.
      In vivo fluorescence imaging indicated accumulation in the tumor area and
      histological studies revealed predominant uptake of the micelles at the margins
      of the tumor, thereby allowing the delineation of its volume. 

PMID- 26307178
TI  - Women's Endorsement of Different Models of Sexual Functioning Supports Polythetic
      Criteria of Female Sexual Interest/Arousal Disorder in DSM-5.

PMID- 26307175
TI  - Proteomics of the Synapse--A Quantitative Approach to Neuronal Plasticity.
AB  - The advances in mass spectrometry based proteomics in the past 15 years have
      contributed to a deeper appreciation of protein networks and the composition of
      functional synaptic protein complexes. However, research on protein dynamics
      underlying core mechanisms of synaptic plasticity in brain lag far behind. In
      this review, we provide a synopsis on proteomic research addressing various
      aspects of synaptic function. We discuss the major topics in the study of protein
      dynamics of the chemical synapse and the limitations of current methodology. We
      highlight recent developments and the future importance of multidimensional
      proteomics and metabolic labeling. Finally, emphasis is given on the conceptual
      framework of modern proteomics and its current shortcomings in the quest to gain
      a deeper understanding of synaptic plasticity. 

PMID- 26307177
TI  - Association of HLA-DRB1 genetic variants with the persistence of atopic
      dermatitis.
AB  - Atopic dermatitis (AD) is a waxing and waning illness of childhood that is likely
      caused by interactions between an altered skin barrier and immune dysregulation.
      The goal of our study was to evaluate the association of DRB1 genetic variants
      and the persistence of AD using whole exome sequencing and high resolution
      typing. DRB1 was interrogated based on previous reports that utilized high
      throughput techniques. We evaluated an ongoing nation-wide long-term cohort of
      children with AD in which patients are asked every 6months about their medication
      use and their AD symptoms. In total, 87 African-American and 50 European-American
      children were evaluated. Genetic association analysis was performed using a
      software tool focusing on amino acid variable positions shared by HLA-DRB1
      alleles covering the antigen presenting domain. Amino acid variations at position
      9 (pocket 9), position 26, and position 78 (pocket 4) were marginally associated
      with the prevalence of AD. However, the odds ratio was 0.30 (0.14, 0.68; p=0.003)
      for residue 78, 0.27 (0.10, 0.69; p=0.006) for residue 26 and not significant for
      residue 9 with respect to the persistence of AD. In conclusion, amino acid
      variations at peptide-binding pockets of HLA-DRB1 were associated with the
      persistence of AD in African-American children. 

PMID- 26307179
TI  - Is levorphanol a better option than methadone?
AB  - BACKGROUND: Methadone has been a stalwart pharmacologic option for the management
      of opioid drug dependence for many years. It substitutes for opioid agonists and
      possesses certain pharmacokinetic properties that confer characteristics
      preferable to those of other opioids for this application. Methadone is likewise
      used as an option for the treatment of pain, particularly chronic pain. It has a
      spectrum of pharmacodynamic activity, including contributions from non-opioid
      components, that translates to its specific clinical attributes as an analgesic.
      Unfortunately, basic science studies and accumulated clinical experience with
      methadone have revealed some undesirable, and even worrisome, features, including
      issues of safety. The benefit/risk ratio of methadone might be acceptable if
      there was no better alternative, but neither its pharmacokinetic nor
      pharmacodynamic properties are unique to methadone. OBJECTIVE: We review the
      basic and clinical pharmacology of methadone and suggest that levorphanol should
      receive attention as a possible alternative. CONCLUSION: Unlike methadone,
      levorphanol is a more potent NMDA antagonist, possesses a higher affinity for DOR
      and KOR, has a shorter plasma half-life yet longer duration of action, has no
      CYP450 interactions or QTc prolongation risk, can be a viable option in the
      elderly, palliative care, and SCI patients, requires little to no need for co
      administration of adjuvant analgesics, and has potentially a lower risk of drug
      related Emergency Department visits compared to other opioids.

PMID- 26307180
TI  - Fibrous Dysplasia Characterization Using Lacunarity Analysis.
AB  - Fibrous dysplasia (FD) is a developmental anomaly in which the normal medullary
      space of the affected bone is replaced by fibro-osseous tissue. This condition is
      typically encountered in adolescents and young adults. It affects the
      maxillofacial region and it can often cause severe deformity and asymmetry.
      Therefore, accurate diagnosis is critical to determine the appropriate treatment
      of each case. In this sense, computed tomography (CT) is a relevant resource
      among the imaging techniques for correct diagnosis of this condition. Thus, in
      this paper, we propose to analyze fibrous dysplasia through its texture pattern.
      To accomplish this task, we propose to use lacunarity analysis, a multiscale
      method for describing patterns of spatial dispersion. Results indicated lower
      lacunarity values for fibrous dysplasia in comparison to normal bone samples, an
      indication that their texture images are more homogeneous, and a high
      separability between the classes when using principal component analysis (PCA)
      and decision trees for statistical analysis. 

PMID- 26307181
TI  - Long-term use of minimal footwear on pain, self-reported function, analgesic
      intake, and joint loading in elderly women with knee osteoarthritis: A randomized
      controlled trial.
AB  - BACKGROUND: Efforts have been made to retard the progressive debilitating pain
      and joint dysfunction in patients with knee osteoarthritis. We aimed to evaluate
      the therapeutic effect of a low-cost minimalist footwear on pain, function,
      clinical and gait-biomechanical aspects of elderly women with knee
      osteoarthritis. METHODS: Throughout a randomized, parallel and controlled
      clinical trial, fifty-six patients with medial knee osteoarthritis were randomly
      allocated to an intervention (n=28) or control group (n=28), and assessed at
      baseline and after three and six months. The intervention involved wearing
      Moleca((r)) footwear for at least 6h/day, 7 days/week, over 6 months. The pain
      subscale of the Western Ontario and McMaster Universities Osteoarthritis Index
      was the primary outcome. The secondary outcomes were the other subscales,
      Lequesne score, distance walked in 6 min, knee oedema and effusion, knee
      adduction moment and paracetamol intake. Intention-to-treat analysis was
      performed using two-way casewise ANOVA (< .05) and Cohen's d coefficient.
      FINDINGS: Intervention group showed improvement in pain (effect size: 1.41,
      p<.001), function (effect size: 1.22, p=.001), stiffness (effect size: 0.76,
      p=.001), Lequesne score (effect size: 1.07, p<.001), and reduction by 21.8% in
      the knee adduction moment impulse (p=.017) during gait wearing Moleca((r)). The
      analgesic intake was lower in the intervention group. INTERPRETATION: The long
      term use of Moleca((r)) footwear relieves pain, improves self-reported function,
      reduces the knee loading while wearing Moleca((r)), refrains the increase of
      analgesic intake in elderly women with knee osteoarthritis and can be considered
      as a conservative mechanical treatment option. ClinicalTrials.gov (NCT01342458).

PMID- 26307183
TI  - Knowledge translation in biostatistics: a survey of current practices,
      preferences, and barriers to the dissemination and uptake of new statistical
      methods.
AB  - BACKGROUND: The use of standard statistical methods in the medical literature has
      been studied extensively; however, the adoption of new methods has received less
      attention. We sought to understand (i) whether there is a perception that new
      methods are underused, (ii) what the barriers to use of new methods are, (iii)
      what dissemination activities are used, and (iv) user preferences for learning
      about new methods. METHODS: We conducted a cross-sectional survey of members of
      the Statistical Society of Canada (SSC) and of principal investigators (knowledge
      users) funded by the Canadian Institutes of Health Research (CIHR). RESULTS:
      There were 157 CIHR respondents (14% response rate), and 39 respondents were
      statisticians from the Statistical Society of Canada. Seventy percent of CIHR
      respondents and 82% of statisticians felt that new developments were under-used.
      Barriers to use of new methods included lack of access to the necessary expertise
      (selected by over 90% of respondents), lack of suitable software (selected by 81%
      of statisticians), and lack of time to implement new methods (selected by 78% of
      statisticians). Greater access to statistical colleagues with an interest in
      collaboration and availability of software to implement new methods were the top
      rated preferences among knowledge-users. CONCLUSIONS: There was a clear
      perception among all respondents that new statistical methods are underused.
      Encouraging statistical methodologists to develop a knowledge translation plan
      for improved dissemination and uptake, placing greater value on the role of the
      statistical collaborator in research, and providing software alongside new
      methods may improve the use of newly developed statistical methods.

PMID- 26307182
TI  - Clinical outcome and predictors of treatment response in foam sodium tetradecyl
      sulfate sclerotherapy of venous malformations.
AB  - OBJECTIVES: To evaluate clinical outcomes and their predictors in patients with
      venous malformation (VM) treated with foam sodium tetradecyl sulfate (STS)
      sclerotherapy. METHODS: We retrospectively evaluated clinical outcomes of foam
      STS sclerotherapy in 86 patients with 91 VMs to assess reduction in pain and mass
      after treatment. Univariate and multivariate analysis was performed to determine
      possible predictors of clinical outcome with foam STS sclerotherapy. RESULTS: A
      positive response of 49.5% in pain reduction and 52.7% in mass reduction was
      observed. The numerical rating scale (NRS) score improved from 4.36 +/- 2.64 to
      1.74 +/- 1.57, and VM mass volume decreased to 41.7 +/- 35.52% of the initial
      size. On multivariate analysis, a high baseline NRS score (odds ratio: 1.12, 95%
      confidence interval: 1.09-1.15) and VM location in the trunk versus the head and
      neck (odds ratio: 1.30, 95% confidence interval: 1.00-1.69) were positive
      predictors of pain improvement. Minor complications occurred in 11 (12.1%)
      patients and recurrence in 12 (13.2%) patients. CONCLUSIONS: Foam STS
      sclerotherapy is an effective treatment in venous malformation, with low
      complication risk. A high baseline NRS score and location in the trunk versus the
      head and neck were positive predictors in improvement of pain. KEY POINTS: * Foam
      STS sclerotherapy is effective in VM, with low risk of complications. * Relief of
      pain tends to be dramatic in patients with severe pain. * Location of VM is a
      predictor of pain improvement. * The presence of a draining vein does not affect
      foam sclerotherapy.

PMID- 26307184
TI  - A Clinical Algorithm for Early Identification and Intervention of Cervical
      Muscular Torticollis.
AB  - Congenital muscular torticollis (CMT) is a common newborn pediatric muscular
      deformity of the neck. The purpose of this article is to suggest a clinical
      algorithm for pediatric clinicians to promote prompt identification and
      intervention for infants with CMT. Early intervention for a child with CMT at
      less than 1 month of age yields a 98% success rate by 2.5 months of age, with the
      infant achieving near normal range of motion. Intervention initiated at 6 months
      of age or later can require 9 to 10 months of therapy with less success in
      achieving full range of motion of the cervical musculature. The clinical
      algorithm proposed here incorporates the American Physical Therapy Association
      guideline for CMT to optimize outcomes for the child and reduce health care
      expenditures. Current evidence and guidelines demonstrate that primary care
      providers are the primary diagnostic clinicians, while physical therapists are
      the preferred provider for the treatment of CMT. 

PMID- 26307185
TI  - "Beat the Shock Clock": An Interprofessional Team Improves Pediatric Septic Shock
      Care.
AB  - Ideal care for septic shock (SS) is difficult. This interprofessional quality
      improvement intervention in a mid-volume pediatric emergency department aimed to
      reduce time to vascular access, fluid resuscitation, and antibiotics for SS.
      Intensive education, a care pathway, and an order set were applied. Outcome
      measures for patients with criteria for SS before and after intervention were
      compared. There were 43 patients pre-intervention (January 2009 to June 2011) and
      63 post-intervention (June 2012 to June 2013). Median time to vascular access
      decreased from 37 minutes pre-intervention to 24 minutes post-intervention (p =
      0.05). Median time to first fluid bolus decreased from 35 to 26 minutes (p =
      0.08). Percentage of boluses delivered rapidly by pressure method increased from
      21% to 74% (p < 0.0001). Median time to antibiotics decreased from 92 to 55
      minutes (p = 0.02). In conclusion, a multimodal, interprofessional quality
      improvement intervention in a mid-sized pediatric emergency department improved
      the time to critical interventions for SS.

PMID- 26307186
TI  - Extracranial contamination in the INVOS 5100C versus the FORE-SIGHT ELITE
      cerebral oximeter: a prospective observational crossover study in volunteers.
AB  - PURPOSE: Previous studies have found that most cerebral oximeters are subject to
      inaccuracies secondary to extracranial contamination of the cerebral oximetric
      signals. We hypothesized that the more advanced second-generation FORE-SIGHT
      ELITE cerebral oximeter would be significantly less affected by extracranial
      tissue hypoxemia than the more widely used first-generation INVOSTM 5100C
      monitor. METHODS: Twenty healthy volunteers aged 18-45 yr had the INVOS and FORE
      SIGHT probes placed on their forehead in a random sequence while in the supine
      position. A pneumatic head cuff was then placed around each volunteer's head just
      below both the oximeter and a concomitantly placed scalp forehead pulse oximeter
      probe. The subjects' scalp cerebral oxygen saturation (SctO2) values were
      measured and compared using the two different devices in sequence, both before
      and after scalp tissue ischemia was induced by the pneumatic cuff. RESULTS:
      Extracranial ischemia resulted in a significant reduction in SctO2 values from
      baseline in both devices. The INVOS 5100C recorded a median [interquartile range]
      decrease in SctO2 from baseline at five minutes of 15.1% [12.6 - 17.6], while
      that recorded by the FORESIGHT ELITE device was 8.6% [4.0 -12.3] at five minutes
      (median difference, 7.9%; 99% confidence interval, 1.9 to 16.5; P = 0.002).
      CONCLUSION: Updated technological algorithms employed in the FORE-SIGHT ELITE
      cerebral oximeter may be responsible for less extracranial contamination than was
      observed in the previous-generation INVOS 5100C device. The impact that this
      extracranial contamination may have on the clinical use of these devices remains
      to be determined.

PMID- 26307187
TI  - Tranexamic acid: When is enough (data) enough?

PMID- 26307188
TI  - Optimizing depth of sedation for colonoscopy.

PMID- 26307189
TI  - Ultrasound-guided internal jugular vein cannulation: techniques to confirm
      guidewire location.

PMID- 26307190
TI  - In reply: Ultrasound-guided internal jugular vein cannulation: techniques to
      confirm guidewire location.

PMID- 26307191
TI  - Identifying factors of activities of daily living important for cost and
      caregiver outcomes in Alzheimer's disease.
AB  - BACKGROUND: We aimed to obtain a better understanding of how different aspects of
      patient functioning affect key cost and caregiver outcomes in Alzheimer's disease
      (AD). METHODS: Baseline data from a prospective observational study of community
      living AD patients (GERAS) were used. Functioning was assessed using the
      Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale.
      Generalized linear models were conducted to analyze the relationship between
      scores for total activities of daily living (ADL), basic ADL (BADL), instrumental
      ADL (IADL), ADL subdomains (confirmed through factor analysis) and individual ADL
      questions, and total societal costs, patient healthcare and social care costs,
      total and supervision caregiver time, and caregiver burden. RESULTS: Four
      distinct ADL subdomains were confirmed: basic activities, domestic/household
      activities, communication, and outside activities. Higher total societal costs
      were associated with impairments in all aspects of ADL, including all subdomains;
      patient costs were associated with total ADL and BADL, and basic activities
      subdomain scores. Both total and supervision caregiver hours were associated with
      total ADL and IADL scores, and domestic/household and outside activities
      subdomain scores (greater hours associated with greater functional impairments).
      There was no association between caregiver burden and BADL or basic activities
      subdomain scores. The relationship between total ADL, IADL, and the outside
      activities subdomain and outcomes differed between patients with mild and
      moderate-to-severe AD. CONCLUSIONS: Identification of ADL subdomains may lead to
      a better understanding of the association between patient function and costs and
      caregiver outcomes at different stages of AD, in particular the outside
      activities subdomain within mild AD.

PMID- 26307192
TI  - Multifaceted roles of adiponectin in rheumatoid arthritis.
AB  - Adiponectin is a circulating hormone with pleiotropic functions in lipid and
      glucose metabolism secreted by adipocytes. It plays a beneficial role in
      cardiovascular functions and metabolic complications. Recently, growing
      researches have elucidated that increased adiponectin plasma levels correlate
      with severity of rheumatoid arthritis (RA) and it is speculative that adiponectin
      may link to RA. The association of adiponectin with potential inflammatory
      functions in RA has raised significant interests in exploring this adipokine as a
      target for RA-diagnostic and therapeutic applications. Despite significant
      advances in understanding adiponectin functions and signaling mechanisms, its
      roles in RA remain multifaceted and subject to controversy. This review
      highlights the evidences linking adiponectin to either anti-inflammatory or pro
      inflammatory action in RA. The results of this review may provide important
      insight into adiponectin in the development of RA. 

PMID- 26307195
TI  - Alphavirus vectors as tools in neuroscience and gene therapy.
AB  - Alphavirus-based vectors have been engineered for in vitro and in vivo expression
      of heterelogous genes. The rapid and easy generation of replication-deficient
      recombinant particles and the broad range of host cell infection have made
      alphaviruses attractive vehicles for applications in neuroscience and gene
      therapy. Efficient delivery to primary neurons and hippocampal slices has allowed
      localization studies of gene expression and electrophysiological recordings of
      ion channels. Alphavirus vectors have also been applied for in vivo delivery to
      rodent brain. Due to the strong local transient expression provided by alphavirus
      vectors a number of immunization and gene therapy approaches have demonstrated
      both therapeutic and prophylactic efficacy in various animal models. 

PMID- 26307194
TI  - Tissue microchimerism is increased during pregnancy: a human autopsy study.
AB  - Microchimerism is the occurrence of small populations of cells with a different
      genetic background within an individual. Tissue microchimerism is considered to
      be primarily pregnancy-derived and is often studied relative to female-dominant
      autoimmune diseases, pregnancy complications, malignancies, response to injury,
      and transplantation outcomes. A particular distribution pattern of chimeric cells
      across various organs was recently described in a model of murine pregnancies.
      Our aim was to determine the frequency and distribution of tissue microchimerism
      across organs during and after pregnancy in humans. We performed in situ
      hybridization of the Y chromosome on paraffin-embedded autopsy samples of
      kidneys, livers, spleens, lungs, hearts and brains that were collected from 26
      women who died while pregnant or within 1 month after delivery of a son.
      Frequencies of chimeric cells in various tissues were compared with those of a
      control group of non-pregnant women who had delivered sons. Tissue microchimerism
      occurred significantly more frequently in the lungs, spleens, livers, kidneys and
      hearts of pregnant women compared with non-pregnant women (all P < 0.01). We
      showed that some of the chimeric cells were CD3+ or CD34+. After correction for
      cell density, the lung was most chimeric (470 Y chromosome-positive nuclei per
      million nuclei scored), followed by the spleen (208 Y+/10(6) nuclei), liver (192
      Y+/10(6) nuclei), kidney (135 Y+/10(6) nuclei), brain (85 Y+/10(6) nuclei) and
      heart (40 Y+/10(6) nuclei). Data from this unique study group of women who died
      while pregnant or shortly after delivery provide information about the number and
      physiologic distribution of chimeric cells in organs of pregnant women. We
      demonstrate that during pregnancy, a boost of chimeric cells is observed in
      women, with a distribution across organs, that parallels findings in mouse
      models.

PMID- 26307196
TI  - Heterogeneity: The key to failure forecasting.
AB  - Elastic waves are generated when brittle materials are subjected to increasing
      strain. Their number and energy increase non-linearly, ending in a system-sized
      catastrophic failure event. Accelerating rates of geophysical signals (e.g.,
      seismicity and deformation) preceding large-scale dynamic failure can serve as
      proxies for damage accumulation in the Failure Forecast Method (FFM). Here we
      test the hypothesis that the style and mechanisms of deformation, and the
      accuracy of the FFM, are both tightly controlled by the degree of microstructural
      heterogeneity of the material under stress. We generate a suite of synthetic
      samples with variable heterogeneity, controlled by the gas volume fraction. We
      experimentally demonstrate that the accuracy of failure prediction increases
      drastically with the degree of material heterogeneity. These results have
      significant implications in a broad range of material-based disciplines for which
      failure forecasting is of central importance. In particular, the FFM has been
      used with only variable success to forecast failure scenarios both in the field
      (volcanic eruptions and landslides) and in the laboratory (rock and magma
      failure). Our results show that this variability may be explained, and the
      reliability and accuracy of forecast quantified significantly improved, by
      accounting for material heterogeneity as a first-order control on forecasting
      power. 

PMID- 26307193
TI  - Discovery of a new method for potent drug development using power function of
      stoichiometry of homomeric biocomplexes or biological nanomotors.
AB  - INTRODUCTION: Multidrug resistance and the appearance of incurable diseases
      inspire the quest for potent therapeutics. AREAS COVERED: We review a new
      methodology in designing potent drugs by targeting multi-subunit homomeric
      biological motors, machines or complexes with Z > 1 and K = 1, where Z is the
      stoichiometry of the target, and K is the number of drugged subunits required to
      block the function of the complex. The condition is similar to a series
      electrical circuit of Christmas decorations: failure of one light bulb causes the
      entire lighting system to lose power. In most multi-subunit, homomeric biological
      systems, a sequential coordination or cooperative action mechanism is utilized,
      thus K equals 1. Drug inhibition depends on the ratio of drugged to non-drugged
      complexes. When K = 1, and Z > 1, the inhibition effect follows a power law with
      respect to Z, leading to enhanced drug potency. The hypothesis that the potency
      of drug inhibition depends on the stoichiometry of the targeted biological
      complexes was recently quantified by Yang-Hui's Triangle (or binomial
      distribution), and proved using a highly sensitive in vitro phi29 viral DNA
      packaging system. Examples of targeting homomeric bio-complexes with high
      stoichiometry for potent drug discovery are discussed. EXPERT OPINION: Biomotors
      with multiple subunits are widespread in viruses, bacteria and cells, making this
      approach generally applicable in the development of inhibition drugs with high
      efficiency.

PMID- 26307197
TI  - Integrative computational mRNA-miRNA interaction analyses of the autoimmune
      deregulated miRNAs and well-known Th17 differentiation regulators: An attempt to
      discover new potential miRNAs involved in Th17 differentiation.
AB  - Th17 cells are a lineage of CD4(+) T helper cells in immune system which
      differentiate from naive CD4(+) T cells and have demonstrated to play a critical
      role in the pathogenesis of different autoimmune disorders. miRNAs are a novel
      group of non-coding RNAs which participate in post-transcriptional regulation of
      gene expression mostly by pairing with 3'UTR of their mRNA targets and inhibition
      of its translation. It has been demonstrated that miRNAs function in various
      cellular processes such as differentiation, proliferation, and apoptosis. By now,
      several signaling pathways and their downstream positive and negative regulators
      involve in Th17 differentiation have been discovered. Several studies have
      reported the aberrant miRNA expression profile in patients with autoimmune
      disease called autoimmune-deregulated miRNAs. Here, using integrative miRwalk
      database which assembles the data gathered from ten different bioinformatics
      databases designed to predict miRNA-target interaction, we analyzed possible
      targeting effect of "autoimmune-deregulated miRNAs" on prominent positive and
      negative regulators of Th17 differentiation. Our resulting mRNA-miRNA network
      simply nominated several miRNAs with strong possibility which probably may have
      inducing (miR-27b, miR-27a, miR-30c, miR-1, and miR-141) or inhibitory (miR-20b,
      miR-93, miR-20a, miR-152, miR-21, and miR-106a) role in Th17 differentiation by
      targeting negative or positive regulators of Th17 differentiation, respectively.

PMID- 26307198
TI  - Counting Sheep: Sleep Disorders in Children With Autism Spectrum Disorders.
AB  - INTRODUCTION: This article will discuss the prevalence and types of sleep
      disorders experienced by children with autism spectrum disorders (ASDs), the risk
      factors for the development of sleep disorders among children with ASDs, the
      impact of sleep disorders on children with ASDs, and the role of the primary care
      provider (PCP) in diagnosing and treating sleep disorders among children with
      ASDs. METHOD: Review of published literature on the topic. RESULTS: Children with
      ASDs are at risk for the development of chronic sleep disorders, which can have a
      negative impact on behavior. Both behavioral and pharmacological interventions
      exist for the treatment of sleep disorders among children with ASDs, with
      supplemental melatonin being the most widely studied and proven treatment.
      DISCUSSION: PCPs will care for children with ASDs. Therefore, it is vital for
      PCPs to be knowledgeable about this topic and to promptly assess for and manage
      sleep disorders among children with ASDs.

PMID- 26307199
TI  - Computer-assisted liver tumor surgery using a novel semiautomatic and a hybrid
      semiautomatic segmentation algorithm.
AB  - We developed a medical image segmentation and preoperative planning application
      which implements a semiautomatic and a hybrid semiautomatic liver segmentation
      algorithm. The aim of this study was to evaluate the feasibility of computer
      assisted liver tumor surgery using these algorithms which are based on
      thresholding by pixel intensity value from initial seed points. A random sample
      of 12 patients undergoing elective high-risk hepatectomies at our institution was
      prospectively selected to undergo computer-assisted surgery using our algorithms
      (June 2013-July 2014). Quantitative and qualitative evaluation was performed. The
      average computer analysis time (segmentation, resection planning, volumetry,
      visualization) was 45 min/dataset. The runtime for the semiautomatic algorithm
      was <0.2 s/slice. Liver volumetric segmentation using the hybrid method was
      achieved in 12.9 s/dataset (SD +/- 6.14). Mean similarity index was 96.2 % (SD +/
      1.6). The future liver remnant volume calculated by the application showed a
      correlation of 0.99 to that calculated using manual boundary tracing. The 3D
      liver models and the virtual liver resections had an acceptable coincidence with
      the real intraoperative findings. The patient-specific 3D models produced using
      our semiautomatic and hybrid semiautomatic segmentation algorithms proved to be
      accurate for the preoperative planning in liver tumor surgery and effectively
      enhanced the intraoperative medical image guidance.

PMID- 26307200
TI  - Non-contact diagnostic system for sleep apnea-hypopnea syndrome based on
      amplitude and phase analysis of thoracic and abdominal Doppler radars.
AB  - Full-night polysomnography (PSG) has been recognized as the gold standard test
      for sleep apnea-hypopnea syndrome (SAHS). However, PSG examinees are physically
      restrained for the full night by many contact sensors and obtrusive connecting
      cables, inducing mental stress. We developed a non-contact SAHS diagnostic system
      that can detect apneic events without inducing stress in monitored individuals.
      Two Doppler radars were installed beneath the mattress to measure the vibrations
      of the chest and abdomen, respectively. Our system determines apnea and hypopnea
      events when the radar output amplitude decreases by <20 and 70 %, respectively,
      of the amplitude of a normal breath (without SAHS events). Additionally, we
      proposed a technique that detects paradoxical movements by focusing on phase
      differences between thoracic and abdominal movements, and were able to identify
      three types of sleep apnea: obstructive, central, and mixed. Respiratory
      disturbance indexes obtained showed a higher correlation (r = 94 %) with PSG than
      with pulse oximetry (r = 89 %). When predicting the severity of SAHS with an
      apnea-hypopnea index (AHI) of >15/h or >30/h using PSG as a reference, the radar
      system achieved a sensitivity of 96 and 90 %, and a specificity of 100 and 79 %
      with an AHI of >15/h and >30/h, respectively. The proposed radar system can be
      used as an alternative to the current airflow sensor, and to chest and abdomen
      belts for apnea-hypopnea evaluation.

PMID- 26307201
TI  - Biomechanical evaluation of the pathophysiologic developmental mechanisms of
      mitral valve prolapse: effect of valvular morphologic alteration.
AB  - Mitral valve prolapse (MVP) refers to an excessive billowing of the mitral valve
      (MV) leaflets across the mitral annular plane into the left atrium during the
      systolic portion of the cardiac cycle. The underlying mechanisms for the
      development of MVP and mitral regurgitation in association with MV tissue
      remodeling are still unclear. We performed computational MV simulations to
      investigate the pathophysiologic developmental mechanisms of MVP. A parametric MV
      geometry model was utilized for this study. Posterior leaflet enlargement and
      posterior chordal elongation models were created by adjusting the geometry of the
      posterior leaflet and chordae, respectively. Dynamic finite element simulations
      of MV function were performed over the complete cardiac cycle. Computational
      simulations demonstrated that enlarging posterior leaflet area increased large
      stress concentration in the posterior leaflets and chordae, and posterior chordal
      elongation decreased leaflet coaptation. When MVP was accompanied by both
      posterior leaflet enlargement and chordal elongation simultaneously, the
      posterior leaflet was exposed to extremely large prolapse with a substantial lack
      of leaflet coaptation. These data indicate that MVP development is closely
      related to tissue alterations of the leaflets and chordae. This biomechanical
      evaluation strategy can help us better understand the pathophysiologic
      developmental mechanisms of MVP. 

PMID- 26307202
TI  - Biomechanical model of knee collateral ligament injury with six degrees of
      freedom.
AB  - Knee ligament injuries cannot be fully described using simplified joint models or
      by experimentation alone. The study objective was to model the contributions of
      the collateral ligaments over six degrees of freedom (DOF) of knee joint
      articulation to aid the diagnosis of knee ligament injuries. A kinematic model of
      the knee joint with six DOF was developed using the Musculoskeletal Joint
      Modeller software, and the effects of medial collateral ligament (MCL) and
      lateral collateral ligament (LCL) rupture were evaluated. The centres of mass of
      the tibia and femur were determined from their surface geometry, and the
      displacement of the moving tibia was determined by measuring the displacements of
      the attached ligaments with respect to its centre of mass. Compared to an intact
      knee, a tibia without the LCL had higher medial translation and lower valgus
      rotation, while a tibia without the MCL had higher lateral translation and higher
      valgus rotation. At 0 degrees , 30 degrees  and 60 degrees  of flexion, the tibia
      without the LCL had more internal rotation than an intact knee. Understanding the
      complete kinematics of knee joints may improve the diagnosis of ligament injuries
      and guide tissue replacement surgery. Predicting joint behaviour in the clinic
      after treatment might benefit from a combined modelling approach that includes
      both clinicians and basic researchers. 

PMID- 26307203
TI  - Effects of inflow velocity profile on two-dimensional hemodynamic analysis by
      ordinary and ultrasonic-measurement-integrated simulations.
AB  - Two-dimensional ultrasonic-measurement-integrated (2D-UMI) simulation correctly
      reproduces hemodynamics even with an inexact inflow velocity distribution. This
      study aimed to investigate which is superior, a two-dimensional ordinary (2D-O)
      simulation with an accurate inflow velocity distribution or a 2D-UMI simulation
      with an inaccurate one. 2D-O and 2D-UMI simulations were performed for blood flow
      in a carotid artery with four upstream velocity boundary conditions: a velocity
      profile with backprojected measured Doppler velocities (condition A), and
      velocity profiles with a measured Doppler velocity distribution, a parabolic one,
      and a uniform one, magnitude being obtained by inflow velocity estimation
      (conditions B, C, and D, respectively). The error of Doppler velocity against the
      measurement data was sensitive to the inflow velocity distribution in the 2D-O
      simulation, but not in the 2D-UMI simulation with the inflow velocity estimation.
      Among the results in conditions B, C, and D, the error in the worst 2D-UMI
      simulation with condition D was 31 % of that in the best 2D-O simulation with
      condition B, implying the superiority of the 2D-UMI simulation with an inaccurate
      inflow velocity distribution over the 2D-O simulation with an exact one.
      Condition A resulted in a larger error than the other conditions in both the 2D-O
      and 2D-UMI simulations. 

PMID- 26307205
TI  - The relative importance of relative nonlinearity and the storage effect in the
      lottery model.
AB  - Although it is likely that many coexistence mechanisms contribute to maintenance
      of species diversity, most approaches to understanding species coexistence
      proceed as if only one mechanism would be present. In studies of species
      coexistence in a temporally fluctuating environment, the storage effect, believed
      to be the most important coexistence mechanism, has been the focus. Although a
      different coexistence mechanism--relative nonlinearity--is also predicted to
      arise frequently with environmental variation, its effect has been overshadowed
      by the storage effect. The relatively nonlinear growth rates on which the
      mechanism depends arise simply from differences in life history traits. Many
      kinds of temporal variation can then interact with these nonlinearity differences
      to create the relative nonlinearity coexistence mechanism. Much is unknown about
      when this mechanism is important and its total neglect is not justified. Here, we
      use the lottery model to provide a much needed quantitative assessment of the
      relative and combined effects of relative nonlinearity and the storage effect.
      Our analysis takes advantage of recently developed techniques for quantifying
      coexistence mechanisms when multiple mechanisms operate in concert. We find that
      relative nonlinearity is able to contribute substantially to species coexistence
      in the lottery model when two conditions are satisfied: (1) species must differ
      greatly in their adult death rates, (2) sensitivity of recruitment to
      environmental variation must be greater for species with larger adult death
      rates. In addition, relative nonlinearity has a critical role in compensating for
      a weakened storage effect when there is high correlation between species in their
      responses to the varying environment. In some circumstances relative nonlinearity
      is stronger than the storage effect or is even the sole mechanism of coexistence.

PMID- 26307204
TI  - An assessment of sex bias in neurodevelopmental disorders.
AB  - BACKGROUND: Neurodevelopmental disorders such as autism and intellectual
      disability have a sex bias skewed towards boys; however, systematic assessment of
      this bias is complicated by the presence of significant genetic and phenotypic
      heterogeneity of these disorders. METHODS: To assess the extent and
      characteristics of sex bias, we analyzed the frequency of comorbid features, the
      magnitude of genetic load, and the existence of family history within 32,155
      individuals ascertained clinically for autism or intellectual
      disability/developmental delay (ID/DD), including a subset of 8,373 individuals
      carrying rare copy-number variants (CNVs). RESULTS: We find that girls were more
      likely than boys to show comorbid features within both autism (P = 2.9 * 10(-6),
      OR = 1.34) and ID/DD (P = 7.2 * 10(-4), OR = 1.08) cohorts. The frequency of
      comorbid features in ID/DD was higher in boys (1q21.1 deletion, 15q11.2q13.1
      duplication) or girls (15q13.3 deletion, 16p11.2 deletion) carrying specific CNVs
      associated with variable expressivity while such differences were the smallest
      for syndromic CNVs (Smith-Magenis syndrome, DiGeorge syndrome). The extent of the
      male sex bias also varied according to the specific comorbid feature, being most
      extreme for autism with psychiatric comorbidities and least extreme for autism
      comorbid with epilepsy. The sex ratio was also specific to certain CNVs, from an
      8:1 male:female ratio observed among autistic individuals carrying the 22q11.2
      duplication to 1.3:1 male:female ratio in those carrying the 16p11.2 deletion.
      Girls carried a higher burden of large CNVs compared to boys for autism or ID/DD,
      and this difference diminished when severe comorbidities were considered.
      Affected boys showed a higher frequency of neuropsychiatric family histories such
      as autism (P = 0.01) or specific learning disability (P = 0.03), while affected
      girls showed a higher frequency of developmental family histories such as growth
      abnormalities (P = 0.02). CONCLUSIONS: The sex bias within neurodevelopmental
      disorders is influenced by the presence of specific comorbidities, specific CNVs,
      mutational burden, and pre-existing family history of neurodevelopmental
      phenotypes.

PMID- 26307207
TI  - A surface-adaptive nanocarrier to prolong circulation time and enhance cellular
      uptake.
AB  - Based on the protonation/deprotonation of poly(beta-amino ester) (PAE), mixed
      shell micelles (MSMs) with adaptive surfaces could rapidly and reversibly change
      surface properties to prolong circulation time in blood (pH 7.4) and enhance
      cellular uptake at tumor sites (pH 6.5). 

PMID- 26307206
TI  - Impact of Rosuvastatin in Contrast-Induced Acute Kidney Injury in the Elderly:
      Post Hoc Analysis of the PRATO-ACS Trial.
AB  - BACKGROUND: Age is a major predictor of contrast-induced acute kidney injury (CI
      AKI). Few studies have focused on CI-AKI in elderly patients with acute coronary
      syndrome (ACS). METHODS: We compare the incidence of CI-AKI in patients <75 and
      >=75 years enrolled in the Protective effect of Rosuvastatin and Antiplatelet
      Therapy On contrast-induced acute kidney injury and myocardial damage in patients
      with ACS (PRATO-ACS) study and explore the impact of high-dose rosuvastatin on CI
      AKI and clinical outcomes in the 2 age-groups. Statin-naive patients with non-ST
      segment elevation ACS scheduled for early invasive strategy (total 504) were
      randomized to rosuvastatin (40 mg on admission followed by 20 mg/day) or no
      statin treatment. Contrast-induced acute kidney injury was defined as creatinine
      increase >=0.5 mg/dL or >=25% above baseline within 72 hours after contrast
      administration. All patients were stratified in tertiles according to baseline
      high-sensitivity C-reactive protein (hs-CRP). RESULTS: Rate of CI-AKI was
      significantly higher in patients >=75 years (15.9% vs 8.7%, odds ratio: 2.001;
      95% confidence interval: 1.14-3.53, P = .015). No significant interaction was
      observed between age and statin treatment (P = .17). Pretreatment with
      rosuvastatin was associated with 65% relative reduction in CI-AKI rate (22/170
      [12.9%] vs 8/177 [4.5%], P = .007) in younger patients and 38% (16/82 [19.5%] vs
      9/75 [12%], P = .20) in the elderly individuals. The greatest protective effect
      of statin treatment was achieved in patients with the highest hs-CRP values in
      both age-groups. CONCLUSION: Patients >=75 years with ACS had a higher risk of
      developing CI-AKI. Early high-dose rosuvastatin is efficacious in reducing kidney
      injury in all patients, especially those with the highest baseline hs-CRP values.

PMID- 26307208
TI  - Cross-cultural adaptation and validation of the Japanese version of the Toronto
      Extremity Salvage Score (TESS) for patients with malignant musculoskeletal tumors
      in the lower extremities.
AB  - BACKGROUND: Before this work a Japanese version of the Toronto Extremity Salvage
      Score (TESS), a disease-specific patient-completed questionnaire widely used to
      assess the physical function of patients with musculoskeletal tumors, had not
      been developed. The purpose of this study was cross-cultural adaptation and
      validation of the English-language version of the TESS to facilitate
      international comparisons of treatment results. METHODS: The TESS was translated
      into Japanese, back-translated into English, and reviewed by a committee to
      develop a consensus Japanese version of the TESS. One hundred and two patients
      were assessed by use of this Japanese version to examine its reliability and
      validity. RESULTS: Test-retest reliability and internal consistency determined by
      using the intraclass correlation coefficient (0.941) and Cronbach's alpha test
      (0.978), respectively, were excellent. Factor analysis showed that the structure
      consisted of a three-item cluster; the Akaike information criterion (AIC) network
      also demonstrated that the items could be divided into three domains in
      accordance with their content. The Japanese version of the TESS correlated with
      the Musculoskeletal Tumor Society rating scale (r = 0.811; P < 0.001) and the
      Short Form-36 physical component summary (r = 0.785; P < 0.001). CONCLUSIONS: Our
      study suggested that the Japanese version of the TESS is a reliable and valid
      instrument for measuring patient-reported functional outcome for patients with
      lower extremity sarcoma, and that it enables international comparisons of
      treatment results. The spatial association of each item demonstrated by using the
      AIC network also suggested that the underlying structure of the TESS reflected
      its coverage of a wide range of physical functions.

PMID- 26307209
TI  - Management of Sleep Quality and Pain in an Individual Living with HIV and
      Hepatitis C Coinfection Using an Activity Monitor.
AB  - STUDY DESIGN: Case report. BACKGROUND: Twenty-five percent of people living with
      HIV/AIDS (PLWHA) are also coinfected with hepatitis C virus (HCV). There are
      limited reports to assist in the symptom management of PLWHA and HCV coinfection.
      CASE DESCRIPTION: Our case was a 67-year-old man living with HIV/HCV coinfection
      and other medical complications. Our intervention consisted of a 6-week
      progressive conditioning program, while his activity and sleep pattern were
      monitored using a wrist accelerometer. OUTCOMES: After completing a conditioning
      training, there was a 64% decrease in the number of waking episodes per night and
      68% decrease in activity at night. Based on Pittsburgh Sleep Quality Index
      scores, the participant transitioned from being a "poor sleeper" to a "good
      sleeper." A 40% decrease in pain was reported. Functional outcome measures also
      showed improvements. DISCUSSION: There were improvements in the participant's
      sleep quality and pain. The use of a commercial accelerometer may assist in
      objectively tracking compliance and activity changes.

PMID- 26307210
TI  - Anal Cancer Screening in an Urban HIV Clinic: Provider Perceptions and Practice.
AB  - In this article, we sought to understand the perceptions and practice of
      providers on anal cancer screening in HIV-infected patients. Providers in an
      academic outpatient HIV practice were surveyed. Data were analyzed to determine
      the acceptability and perceptions of providers on anal Papanicolaou tests. Survey
      response rate was 55.3% (60.7% among male and 47.4% among female providers). One
      third of the providers had received screening requests from patients. Female
      providers had higher self-rated comfort with anal Papanicolaou tests, with a mean
      score of 7.1 (95% confidence interval [CI] 4.7-9.5) compared to 3.6 (95% CI 1.5
      5.7) for male providers, P = .02. Sixty-seven percent of male providers and 37.5%
      of female providers would like to refer their patients for screening rather than
      perform the test themselves. Only 54.2% of our providers have ever performed anal
      cytology examination. Our survey revealed that not all providers were comfortable
      performing anal cancer screening for their patients. 

PMID- 26307211
TI  - Features of Metabolic Syndrome and Its Associated Factors during Highly Active
      Antiretroviral Therapy in Ouagadougou (Burkina Faso).
AB  - BACKGROUND: To study the features of metabolic syndrome (MS) and its associated
      factors during highly active antiretroviral therapy (HAART), in Ouagadougou.
      METHODS: It was a cross-sectional study from March to November 2011 in Yalgado
      Ouedraogo hospital. A nonprobability sample of adults receiving antiretroviral
      drugs for at least 6 months was studied. Pregnancy, ascites, or abdominal mass
      were noninclusion criteria. Metabolic syndrome met the criteria of International
      Diabetes Federation 2005. RESULTS: The authors studied 300 patients. Metabolic
      syndrome was diagnosed in 54 (18%) patients: mean age 44.8 +/- 7.4 years, sex
      ratio 0.17, and mean duration of HAART 71 +/- 30.9 months. The current anomaly of
      MS was low high-density lipoprotein (HDL)-cholesterol in 37 patients (68.5%), and
      the common profile of MS was high waist circumference + low HDL-cholesterol +
      abnormal blood pressure (29.6%). Associated factors were protease inhibitor
      regimens (P = .000), female gender (P = .004), age > 42 years (P = .001), and
      lipodystrophy (P = .01). CONCLUSION: Cardiovascular risks should be regarded
      during the care of HIV-infected patients.

PMID- 26307213
TI  - Blending Cr2O3 into a NiO-Ni electrocatalyst for sustained water splitting.
AB  - The rising H2 economy demands active and durable electrocatalysts based on low
      cost, earth-abundant materials for water electrolysis/photolysis. Here we report
      nanoscale Ni metal cores over-coated by a Cr2 O3 -blended NiO layer synthesized
      on metallic foam substrates. The Ni@NiO/Cr2 O3 triphase material exhibits
      superior activity and stability similar to Pt for the hydrogen-evolution reaction
      in basic solutions. The chemically stable Cr2 O3 is crucial for preventing
      oxidation of the Ni core, maintaining abundant NiO/Ni interfaces as catalytically
      active sites in the heterostructure and thus imparting high stability to the
      hydrogen-evolution catalyst. The highly active and stable electrocatalyst enables
      an alkaline electrolyzer operating at 20 mA cm(-2) at a voltage lower than 1.5 V,
      lasting longer than 3 weeks without decay. The non-precious metal catalysts
      afford a high efficiency of about 15 % for light-driven water splitting using
      GaAs solar cells. 

PMID- 26307212
TI  - Development of an mHealth Intervention (iSTEP) to Promote Physical Activity among
      People Living with HIV.
AB  - A randomized controlled trial is being conducted in the United States to test the
      efficacy of a personalized interactive mobile health intervention (iSTEP)
      designed to increase physical activity (PA) and improve neurocognitive
      functioning among HIV-positive persons. This article describes an initial
      qualitative study performed to develop iSTEP for the HIV-positive population,
      including assessment of PA barriers and facilitators. Two focus groups, with 9
      and 12 unique HIV-positive individuals, respectively, were administered to
      evaluate barriers limiting PA and potential iSTEP content created to encourage
      greater PA. Group discussions revealed prominent PA barriers, including HIV
      symptoms (neuropathy, lipoatrophy), antiretroviral medication effects, and
      fatigue; significant PA facilitators included self-monitoring and family support.
      Participants provided feedback on strategies to increase PA and expressed
      positive support for a mobile intervention adapted to personal priorities. These
      findings will assist the development of novel PA interventions focused on
      treating the epidemic of HIV-associated neurocognitive disorders. 

PMID- 26307214
TI  - Haloalkaliphilic Streptomyces spp. AJ8 isolated from solar salt works and its'
      pharmacological potential.
AB  - Antagonistic Streptomyces spp. AJ8 was isolated and identified from the Kovalam
      solar salt works in India. The antimicrobial NRPS cluster gene was characterized
      by PCR, sequencing and predict the secondary structure analysis. The secondary
      metabolites will be extracted from different organic solvent extraction and
      studied the antibacterial, antifungal, antiviral and anticancer activities. In
      vitro antagonistic activity results revealed that, Streptomyces spp. AJ8 was
      highly antagonistic against Staphylococcus aureus, Aeromonas hydrophila WPD1 and
      Candida albicans. The genomic level identification revealed that, the strain was
      confirmed as Streptomyces spp. AJ8 and submitted the NCBI database (KC603899).
      The NRPS gene was generated a single gene fragment of 781 bp length (KR491940)
      and the database analysis revealed that, the closely related to Streptomyces spp.
      SAUK6068 and S. coeruleoprunus NBRC15400. The secondary metabolites extracted
      with ethyl acetate was effectively inhibited the bacterial and fungal growth at
      the ranged between 7 and 19.2 mm of zone of inhibition. The antiviral activity
      results revealed that, the metabolite was significantly (P < 0.001) controlled
      the killer shrimp virus white spot syndrome virus at the level of 85 %. The
      metabolite also suppressed the L929 fibroblast cancer cells at 35.7 % viability
      in 1000 ug treatment. 

PMID- 26307215
TI  - [Treatment of heredodegenerative retinal disorders now and in the future].

PMID- 26307218
TI  - Denominators Matter.

PMID- 26307219
TI  - Musculoskeletal Ultrasonography to Distinguish Muscle Changes in Complex Regional
      Pain Syndrome Type 1 from Those of Neuropathic Pain: An Observational Study.
AB  - Musculoskeletal ultrasonography (MSK USG) can identify myofascial structural
      lesions. We describe in this retrospective report the observational findings of
      USG data of muscles from limbs affected with neuropathic pain in 7 patients and
      compare them with muscles affected with complex regional pain syndrome type 1
      (CRPS-1) in 7 patients. We highlight findings that distinguish between the 2
      conditions. Musculoskeletal ultrasonography of muscles in CRPS was characterized
      by a variable or/and global intramuscular structural disruption with loss of
      muscle bulk. Adjacent muscles coalesced with one another to present an uniform
      hyperechogenic mass of tissue. Muscle edema was found in some patients. In
      comparison, MSK USG in muscles affected by neuropathic pain exhibited structural
      normalcy, but also showed considerable reduction in muscle bulk. Musculoskeletal
      ultrasonography shows promise as a diagnostic modality to distinguish between
      these 2 conditions which presently have only clinical diagnostic criteria to aid
      diagnosis. 

PMID- 26307223
TI  - Psychosocial correlates of alcohol use and heavy episodic drinking among Italian
      adolescents: Data from the second International Self-Reported Delinquency study.
AB  - BACKGROUND AND OBJECTIVES: To provide a comprehensive picture of the wide
      spectrum of psychosocial factors potentially associated with alcohol consumption
      and problematic drinking among Italian adolescents in order to encourage debate
      on the context-specificity or universality of psychosocial correlates of
      adolescent alcohol use and misuse across countries and cultures. METHODS: The
      International Self-Report Delinquency survey questionnaire was used to assess
      several variables concerning sociodemographic background, family relationships
      and problems, school performance and climate, life events, victimization
      experiences, neighborhood climate, personality traits, and attitudes, delinquent
      behavior, drug use, and peers behavior in a city-based sample of 6,363 seventh to
      ninth grade Italian students. RESULTS: Generalized linear regression models
      showed that recent alcohol consumption and heavy episodic drinking were
      associated with multiple factors pertaining to different levels and domains
      reflecting the adolescent's personality and behavior as well as the different
      social and cultural contexts in which adolescents spend most of their time. Poor
      relations with parents, parental divorce, positive attitudes toward violence, and
      low self-control appeared to precede recent alcohol use and misuse and might be
      potential risk factors for alcohol use and/or misuse, while the association
      between problematic drinking and deviant attitudes (i.e., violent behavior, drug
      use, and affiliation with deviant peers) might be explained through reciprocal
      influences. DISCUSSION AND CONCLUSIONS: Some psychosocial correlates of
      adolescent alcohol use and misuse might be universal across countries and
      cultures. Additionally, certain family, school, personality, behavioral, and peer
      related factors might be more important than other correlates of youth alcohol
      use.

PMID- 26307228
TI  - Iron deposition influences the measurement of water diffusion tensor in the human
      brain: a combined analysis of diffusion and iron-induced phase changes.
AB  - INTRODUCTION: This study aims to evaluate the impact of iron deposition during
      aging on the measurement of water diffusion in the brain. METHODS: Diffusion
      tensor images (DTI) and phase images collected from a group of healthy adults
      from 23 to 72 years old were retrospectively analyzed. The axial diffusivity,
      radial diffusivity, mean diffusivity (MD), and fractional anisotropy (FA) in the
      frontal white matter and deep gray matter nuclei were calculated. The phase
      changes in these regions were used to estimate local iron concentration. Pearson
      correlation analysis was used to evaluate the age dependence of DTI metrics and
      iron concentration. Multiple linear regression models were then built to examine
      the independent effect of age and iron deposition on DTI metrics. RESULTS: Age
      related iron deposition occurred in the putamen (r = 0.680, P < 0.001) and
      frontal white matter (r = 0.333, P = 0.007). In the putamen, FA increased with
      elevated iron concentration (P = 0.042) excluding the effect of age, and MD
      decreased with iron deposition with marginal statistical significance (P =
      0.067). In the frontal white matter, increase in iron level was also associated
      with a decrease in MD and an increase in FA. Moreover, radial diffusivity was
      more reduced than axial diffusivity as local iron concentration increased.
      CONCLUSION: Iron deposition in the brain during aging decreases water diffusion
      and increases the degree of anisotropy. Caution is needed when using DTI metrics
      for diagnosis of various neurological diseases involving abnormal iron
      deposition.

PMID- 26307229
TI  - Drug release, preclinical and clinical pharmacokinetics relationships of alginate
      pellets prepared by melt technology.
AB  - INTRODUCTION: Alginate pellets prepared by the aqueous agglomeration technique
      experience fast drug dissolution due to the porous pre-formed calcium alginate
      microstructure. OBJECTIVE: This study investigated in vitro drug release,
      preclinical and clinical pharmacokinetics relationships of intestinal-specific
      calcium acetate-alginate pellets against calcium-free and calcium carbonate
      alginate pellets. METHOD: Alginate pellets were prepared by solvent-free melt
      pelletization instead of aqueous agglomeration technique using chlorpheniramine
      maleate as model drug. RESULTS: A fast in situ calcium acetate dissolution in
      pellets resulted in rapid pellet breakup, soluble Ca(2+) crosslinking of alginate
      fragments and drug dissolution retardation at pH 1.2, which were not found in
      other pellet types. The preclinical drug absorption rate was lower with calcium
      acetate loaded than calcium-free alginate pellets. In human subjects, however,
      the extent and the rate of drug absorption were higher from calcium acetate
      loaded pellets than calcium-free alginate pellets. The fine, dispersible and
      weakly gastric mucoadhesive calcium alginate pellets underwent fast human
      gastrointestinal transit. They released the drug at a greater rate than calcium
      free pellets in the intestine, thereby promoting drug bioavailability.
      CONCLUSION: Calcium acetate was required as a disintegrant more than as a
      crosslinking agent clinically to promote pellet fragmentation, fast
      gastrointestinal transit and drug release in intestinal medium, and intestinal
      specific drug bioavailability.

PMID- 26307230
TI  - Predictive Potential of Preoperative Nutritional Status in Long-Term Outcome
      Projections for Patients with Gastric Cancer.
AB  - BACKGROUND: Preoperative nutritional status not only correlates with the
      incidence of postoperative complications but also may be indicative of long-term
      outcomes for patients with cancer. The impact of preoperative nutritional status
      on outcomes for patients undergoing gastrectomy for gastric cancer (GC) was
      investigated. METHODS: The study reviewed 594 patients treated for GC by
      gastrectomy at the authors' hospital between January, 2004 and December, 2010.
      Onodera's prognostic nutritional index (PNI) was invoked, using an optimal cut
      point to group patients as having high (PNI > 45; n = 449) or low (PNI <= 45; n =
      145) nutritional status. Clinicopathologic features, perioperative results, and
      long-term outcomes, including cause of death, were compared. RESULTS:
      Multivariate analysis of 5-year overall survival (OS) and disease-specific
      survival (DSS) indicated that low PNI was independently associated with
      unfavorable outcomes for patients with GC. In subgroup analysis, the 5-year OS
      and DSS rates for patients with GC at stages 1 and 2 were significantly worse in
      the low PNI group than in the high PNI group. Although wound and extrasurgical
      field infections also tended to be more frequent in the low PNI group,
      postoperative intraabdominal infections did not differ significantly by group.
      CONCLUSIONS: Preoperative PNI may have merit as a gauge of prognosis for patients
      with GC at stages 1 and 2, but PNI and postoperative morbidity showed no
      correlation in this setting.

PMID- 26307231
TI  - Systematic Review and Meta-Analysis of Enucleation Versus Standardized Resection
      for Small Pancreatic Lesions.
AB  - BACKGROUND: The appropriate surgical strategy in patients with small pancreatic
      lesions of low malignant potential, such as pancreatic neuroendocrine tumors,
      remains unknown. Increasing reports suggest limited pancreatic surgery may be a
      safe option for parenchymal preservation. METHODS: PubMed and MEDLINE were
      searched in the English literature for studies from January 2000 to February 2015
      examining enucleation for pancreatic lesions that were single-arm and comparative
      studies (versus resection). Single-arm enucleation studies were systematically
      reviewed. Comparative studies were included for meta-analysis. Endpoints include
      safety, complications, mortality, survival, and parenchymal-related outcomes.
      RESULTS: Thirteen studies comprising of 1101 patients undergoing enucleation were
      included. Seven studies were comparative studies of enucleation and standardized
      pancreatic resection. Enucleation was a shorter procedure (pooled mean
      differences (MD) = 109, 95 % confidence interval (CI) 105-114; Z = 46.37; P <
      0.001) associated with less blood loss (pooled MD = 314, 95 % CI 297-330; Z =
      37.47; P < 0.001). Both enucleation and resection had similar mortality and
      complication rates, but the rate of pancreatic fistula (all grades) (pooled odds
      ratio (OR) = 1.99; 95 % CI 1.2-3.4; Z = 2.57; P = 0.01] and rate of pancreatic
      fistula (grade B/C) (pooled OR = 1.58; 95 % CI 1.0-2.5; Z = 2.06; P = 0.04) was
      higher in the enucleation group. Enucleation resulted in lower rates of endocrine
      (pooled OR = 0.22; 95 % CI 0.1-0.5; Z = 3.21; P = 0.001) and exocrine (pooled OR
      = 0.07; 95 % CI 0.02-0.2; Z = 5.08; P < 0.001) insufficiency. The median 5-year
      survival was 95 % (range 93-98) and 84 % (range 79-90). CONCLUSIONS: Enucleation
      appears to be a safe procedure and achieves parenchymal preservation for small
      pancreatic lesions of low malignant potential. Its oncologic efficacy compared
      with standardized pancreatic resection with respect to long-term survival and
      recurrences have not been reported adequately and hence may not be concluded as
      being comparable.

PMID- 26307232
TI  - Comparative Study of Liposomal Bupivacaine Versus Paravertebral Block for Pain
      Control Following Mastectomy with Immediate Tissue Expander Reconstruction.
AB  - BACKGROUND: Several approaches to minimize postoperative pain, nausea, and
      enhance recovery are available for patients undergoing mastectomy with immediate
      tissue expander (TE) reconstruction. We compared the effectiveness of
      intraoperative local infiltration of liposomal bupivacaine (LB) to preoperative
      paravertebral block (PVB). METHODS: We retrospectively reviewed patients who
      underwent mastectomy with immediate TE reconstruction between May 2012 and
      October 2014 and compared patients with preoperative ultrasound-guided PVB to
      those with intraoperative LB infiltration. RESULTS: Fifty-three patients (54.6 %)
      received LB and 44 received PVB. LB was associated with less opioid use in the
      recovery room (p < 0.001), fewer patients requiring antiemetics (p = 0.03), and
      lower day of surgery pain scores (p = 0.008). LB also was associated with longer
      time to first opioid use (p = 0.04). On multivariable analysis controlling for
      expander placement location, year of surgery, and axillary lymph node dissection
      (ALND), the only variable that remained statistically significant was lower
      opioid use in the recovery room for patients with LB (p = 0.03) and day of
      surgery pain scores approached significance (p = 0.05). There was no difference
      in the proportion of patients discharged within 36 h of surgery between the
      groups. Focusing on first cases of the day (where PVBs are performed in the OR)
      showed average time to skin incision was 15 min shorter in the LB group (p =
      0.004). CONCLUSIONS: Local infiltration of LB in patients undergoing mastectomy
      with immediate TE reconstruction decreases narcotic requirements in the recovery
      room, shortens preoperative anesthesiology time, and provides similar, if not
      better, perioperative pain control compared with PVB.

PMID- 26307233
TI  - Variation in Additional Breast Imaging Orders and Impact on Surgical Wait Times
      at a Comprehensive Cancer Center.
AB  - BACKGROUND: In the multidisciplinary care model, breast imagers frequently
      provide second-opinion reviews of imaging studies performed at outside
      institutions. However, the need for additional imaging and timeliness of
      obtaining these studies has yet to be established. We sought to evaluate the
      frequency of additional imaging orders by breast surgeons and to evaluate the
      impact of this supplementary imaging on timeliness of surgery. METHODS: We
      identified 2489 consecutive women with breast cancer who underwent first
      definitive surgery (FDS) at our comprehensive cancer center between 2011 and
      2013. The number of breast-specific imaging studies performed for each patient
      between initial consultation and FDS was obtained. chi (2) tests were used to
      quantify the proportion of patients undergoing additional imaging by surgeon.
      Interval time between initial consultation and additional imaging and/or biopsy
      was calculated. The delay of additional imaging on time to FDS was assessed by t
      test. RESULTS: Of 2489 patients, 615 (24.7 %) had at least one additional breast
      specific imaging study performed between initial consultation and FDS, with 222
      patients undergoing additional biopsies (8.9 %). The proportion of patients
      receiving imaging tests by breast surgeon ranged from 15 to 39 % (p < 0.0001).
      Patients receiving additional imaging had statistically longer wait times to FDS
      for BCT (21.4-28.5 days, p < 0.0001). CONCLUSIONS: Substantial variability exists
      in the utilization of additional breast-specific imaging and in the timeliness of
      obtaining these tests among breast surgeons. Further research is warranted to
      assess the sources and impact of this variation on patient care, cost, and
      outcomes.

PMID- 26307234
TI  - Knowledge and attitiudes of pregnant women and their providers towards
      recommendations for immunization during pregnancy.
AB  - OBJECTIVES: Tetanus, diphtheria and acellular pertussis (Tdap) and influenza
      vaccination is recommended during each pregnancy but uptake is suboptimal. We
      evaluated knowledge and acceptance of vaccination recommendations among pregnant
      women. METHODS: Prospective, convenience survey of pregnant women presenting for
      antenatal care at the Pavilion for Women, Texas Children's Hospital, Houston, and
      their healthcare providers. RESULTS: 796 of 825 (96.5%) of women and 63 of 87
      (72.4%) providers completed surveys. Mean age of pregnant women was 30.2 (18-45)
      years. Self-identified race/ethnicity was 45% white, 26% Hispanic, 13% black, 12%
      Asian and 4% other. Most women had college degrees (84%) and private health
      insurance (83%). Mean gestation was 28.5 weeks with 4.8%, 37.8% and 57.4%, in the
      1st, 2nd and 3rd trimesters, respectively. Women used various sources for
      pregnancy information (personal contacts, providers, print, audiovisual and
      online media) but 89.1% cited a provider as their most trusted source,
      predominantly (85.8%) their physician. 668 (84%) knew vaccines are recommended
      during pregnancy, specifically influenza (77%) and Tdap (61%) vaccines. 659 (83%)
      were willing to receive vaccines if recommended by their physician. Factors
      impacting vaccination decisions included safety for baby, safety for mother and
      sufficient information, scoring 4.7, 4.5 and 4.2, respectively, on a 5-point
      scale; less important were additional visit time (2.6), cost (1.9) or needle
      phobia (1). Women surveyed in the 3rd trimester showed greater acceptance than
      those earlier in gestation (87% vs 78%; P0.003). Maternal education, ethnicity,
      insurance, multiple gestation or history of serious illness in a prior infant did
      not affect willingness to receive vaccines. CONCLUSIONS: Pregnant women are
      willing to accept vaccination in pregnancy if recommended by their physician and
      if sufficient discussion of safety and rationale occurs. Strong physician
      recommendation, as reported for pediatric vaccination, is essential to optimizing
      uptake of vaccines during pregnancy.

PMID- 26307235
TI  - Virus replication kinetics and pathogenesis of infection with H7N9 influenza
      virus in isogenic guinea pigs upon intratracheal inoculation.
AB  - Since 2013, avian influenza viruses of subtype H7N9 have been transmitted from
      poultry to humans in China and caused severe disease. Concerns persist over the
      pandemic potential of this virus and further understanding of immunity and
      transmission is required. The isogenic guinea pig model uniquely would allow for
      investigation into both. Eighteen female isogenic guinea pigs 12-16 weeks were
      inoculated intratracheally with either A/H7N9 virus (n=12) or PBS (n=6) and
      sacrificed on days 2 and 7 post-inoculation. Nasal and pharyngeal swabs were
      taken daily to assess viral replication kinetics and necropsies were performed to
      study pathogenesis. All animals showed peak virus titers in nasal secretions at
      day 2 post-inoculation and by day 7 post-inoculation infectious virus titers had
      decreased to just above detectable levels. At day 2, high virus titers were found
      in nasal turbinates and lungs and moderate titers in trachea and cerebrum. At day
      7, infectious virus was detected in the nasal turbinates only. Histology showed
      moderate to severe inflammation in the entire respiratory tract and
      immunohistochemistry (IHC) demonstrated large numbers of viral antigen positive
      cells in the nasal epithelium at day 2 and fewer at day 7 post-inoculation. A
      moderate number of IHC positive cells was observed in the bronchi(oli) and
      alveoli at day 2 only. This study indicates that isogenic guinea pigs are a
      promising model to further study immunity to and transmission of H7N9 influenza
      virus. 

PMID- 26307236
TI  - New Stable and Persistent Acyclic Diaminocarbenes.
AB  - The portfolio of acyclic diaminocarbenes (ADACs) has been substantially expanded,
      owing to the synthesis of eleven new formamidinium salts, mostly of the type
      [(iPr2N)CH(NRR')][PF6], for use as immediate carbene precursors. The
      corresponding ADACs (iPr2N)C(NRR') were sufficiently stable for isolation in the
      case of NRR' = 2-methylpiperidino (13), 3-methylpiperidino (14), 4
      methylpiperidino (15), morpholino (17) and NiPrPh (20), but had to be trapped in
      situ in the case of NRR' = 2,2,6,6-tetramethylpiperidino (12) and NiPrMe (19).
      The tetraaryl-substituted ADACs (Ph2N)2C (22) and (Ph2N)C[N(C6F5)2] (24) also
      could only be generated and trapped in situ. Trapping with elemental selenium was
      particularly efficient, affording the corresponding selenourea derivative in all
      cases, whereas trapping with [{Rh(MU-Cl)(cod)}2] did not work for 12 and 24. The
      (77)Se NMR chemical shifts, delta((77)Se), of the selenourea compounds derived
      from the new ADACs lie in the range 450-760 ppm, which indicates a much higher
      electrophilicity and pi-accepting capability of ADACs in comparison with NHCs,
      which typically exhibit delta((77)Se)<200 ppm. The extreme low-field shift of 758
      ppm observed for 12Se can be rationalised by the results of DFT calculations,
      which revealed that ADAC 12 has a minimum energy conformation with the 2,2,6,6
      tetramethylpiperidino unit perpendicular to the N2C plane, which suppresses the
      pi donation of this amino group and causes an unusually low LUMO energy and high
      electrophilicity.

PMID- 26307237
TI  - Chromosome biology: CTCF-binding site orientation shapes the genome.

PMID- 26307239
TI  - Dyspareunia in a Teenager Reveals a Rare Occurrence: Retroperitoneal Cervical
      Leiomyoma of the Left Pararectal Space.
AB  - BACKGROUND: Retroperitoneal uterine leiomyoma is a very rare occurrence and to
      discover it as a cause of female sexual dysfunction in a teen is unusual. CASE:
      An 18-year-old black woman reported deep dyspareunia, resulting in severe
      distress. Gynecological and instrumental examinations showed a pelvic mass of 7
      cm in diameter. The preoperative diagnosis was uterine fibroid, but the exact
      location of the leiomyoma was uncertain. Laparoscopic examination showed a
      pedunculated retroperitoneal cervical leiomyoma in the left pararectal space.
      After surgical excision of the mass, normal sexual activity was restored. SUMMARY
      AND CONCLUSION: When a teen experiences pain with intercourse, pelvic masses
      should be part of differential diagnosis of dyspareunia.

PMID- 26307238
TI  - Contribution of food prices and diet cost to socioeconomic disparities in diet
      quality and health: a systematic review and analysis.
AB  - CONTEXT: It is well established in the literature that healthier diets cost more
      than unhealthy diets. OBJECTIVE: The aim of this review was to examine the
      contribution of food prices and diet cost to socioeconomic inequalities in diet
      quality. DATA SOURCES: A systematic literature search of the PubMed, Google
      Scholar, and Web of Science databases was performed. STUDY SELECTION:
      Publications linking food prices, dietary quality, and socioeconomic status were
      selected. DATA EXTRACTION: Where possible, review conclusions were illustrated
      using a French national database of commonly consumed foods and their mean retail
      prices. DATA SYNTHESIS: Foods of lower nutritional value and lower-quality diets
      generally cost less per calorie and tended to be selected by groups of lower
      socioeconomic status. A number of nutrient-dense foods were available at low cost
      but were not always palatable or culturally acceptable to the low-income
      consumer. Acceptable healthier diets were uniformly associated with higher costs.
      Food budgets in poverty were insufficient to ensure optimum diets. CONCLUSIONS:
      Socioeconomic disparities in diet quality may be explained by the higher cost of
      healthy diets. Identifying food patterns that are nutrient rich, affordable, and
      appealing should be a priority to fight social inequalities in nutrition and
      health.

PMID- 26307240
TI  - Does Neighborhood Risk Explain Racial Disparities in Low Birth Weight among
      Infants Born to Adolescent Mothers?
AB  - STUDY OBJECTIVE: To test associations and interactions between racial
      identification, neighborhood risk, and low birth weight disparities between
      infants born to African-American and white adolescent mothers. DESIGN:
      Retrospective cross-sectional study. Birth cases were geocoded and linked to
      census tract information from the 2010 US Census and the 2007-2011 American
      Community Survey. A "neighborhood risk" index was created using principal
      component analysis, and mothers were grouped into 3 neighborhood risk levels
      (low, medium, high). Multilevel models with cross-level interactions were used to
      identify variation in racial differences in low birth weight outcomes across
      neighborhood risk levels when controlling for maternal demographic
      characteristics and pregnancy behaviors (smoking, prenatal care use). SETTING:
      North Carolina, United States. PARTICIPANTS: Singleton infants (n = 7923 cases)
      born to non-Hispanic African American and white adolescent mothers from the North
      Carolina State Center of Health Statistics for 2011. MAIN OUTCOME MEASURES: Low
      birth weight. RESULTS: African American mothers were significantly more likely to
      have infants of low birth weight than white mothers in this sample (odds ratio =
      1.89; 95% confidence interval, 1.53-2.34). Mothers that resided in areas of high
      neighborhood risk were significantly more likely to have infants of low birth
      weight than mothers residing in areas of low neighborhood risk (odds ratio =
      1.55; 95% confidence interval, 1.25-1.93). Even when controlling for confounding
      factors, racial disparities in low birth weight odds did not significantly vary
      according to neighborhood risk level. CONCLUSION: Racial disparities can remain
      in low birth weight odds among infants born to adolescent mothers when
      controlling for maternal characteristics, pregnancy behaviors, and neighborhood
      risk.

PMID- 26307242
TI  - Autism, Accommodation and Treatment: A Rejoinder to Chong-Ming Lim's Critique.
AB  - We are very grateful to Chong-Ming Lim for his thoughtful reply published in this
      journal on one of our articles, which motivated us to think more carefully about
      accommodating autistic individuals and treating autism. However we believe there
      are some confusions in Lim's argument. Lim uses the accommodation thesis,
      according to which we should accommodate autistic individuals rather than treat
      autism, as the starting point for his reasoning. He claims that if the
      accommodation thesis is right, then we should not treat autistic individuals for
      their autism, not even low-functioning (i.e. intellectually disabled) ones,
      because this would be disrespectful to all autistic individuals. We should
      instead limit ourselves to accommodate all autistic individuals. However, the
      opposition between accommodation and treatment is not valid in the case of
      autism, because of ambiguity in the concepts of accommodation and treatment.
      Moreover there is confusion in Lim's reasoning caused by omitting important facts
      about the practice of treating autism. 

PMID- 26307241
TI  - Anti-CD20 monoclonal antibody-dependent phagocytosis of chronic lymphocytic
      leukaemia cells by autologous macrophages.
AB  - Unconjugated monoclonal antibodies (mAbs) are an important component of effective
      combination therapies for chronic lymphocytic leukaemia (CLL). Antibody-dependent
      phagocytosis (ADP) is a major mediator of mAb cytotoxicity, but there is limited
      knowledge of the determinants of ADP efficacy. We used macrophages derived in
      vitro from autologous circulating monocytes to test the effects of mAb structure
      and concentration, target : effector cell ratio, duration of co-incubation and
      CLL cell CD20 expression on ADP. Next-generation anti-CD20 mAbs (ofatumumab,
      ublituximab, obinutuzumab, ocaratuzumab) were significantly more effective at
      inducing ADP compared to rituximab, but none were as effective as the anti-CD52
      mAb alemtuzumab. Ofatumumab (10 MUg/ml) used as a representative next-generation
      anti-CD20 mAb achieved an ADP plateau at 3 h co-incubation with a target :
      effector ratio of 10 : 1 (mean = 2.1 CLL cells/macrophage, range = 1.5-3.5). At
      0.156 MUg/ml (the lowest concentration tested) ofatumumab ADP was significantly
      higher than alemtuzumab. However, ofatumumab-induced ADP did not increase
      significantly at higher mAb concentrations. We show that anti-CD20 mAb ADP
      efficacy is determined by the mAb characteristics, target : effector ratio and
      incubation time. We suggest that preclinical evaluation of anti-CD20 mAbs to
      understand the determinants of ADP could be useful in designing future
      combination therapies for CLL.

PMID- 26307244
TI  - Esophagitis dissecans superficialis.

PMID- 26307243
TI  - Differential Susceptibility: The Genetic Moderation of Peer Pressure on Alcohol
      Use.
AB  - Although peer pressure can influence adolescents' alcohol use, individual
      susceptibility to these pressures varies across individuals. The dopamine
      receptor D4 gene (DRD4) is a potential candidate gene that may influence
      adolescents' susceptibility to their peer environment due to the role dopamine
      plays in reward sensation during social interaction. We hypothesized that DRD4
      genotype status would moderate the impact of 7th-grade antisocial peer pressure
      on 12th-grade lifetime alcohol use (n = 414; 58.7% female; 92.8% White). The
      results revealed significant main effects for antisocial peer pressure, but no
      main effects for DRD4 genotype on lifetime alcohol use. Adolescent DRD4 genotype
      moderated the association between peer pressure and lifetime alcohol use. For
      individuals who carried at least one copy of the DRD4 7-repeat allele (7+),
      antisocial peer pressure was associated with increased lifetime alcohol use.
      These findings indicate that genetic sensitivity to peer pressure confers
      increased alcohol use in late adolescence.

PMID- 26307245
TI  - PerCEN trial participant perspectives on the implementation and outcomes of
      person-centered dementia care and environments.
AB  - BACKGROUND: Well-being and various forms of agitation in people with dementia can
      be improved in a person-centered long-term care setting. Data obtained during the
      Person-Centered Dementia Care and Environment (PerCEN) randomized controlled
      trial shed light on the factors that influenced the adoption and outcomes of
      person-centered interventions in long-term care from the perspective of study
      participants. METHODS: Data were obtained from PerCEN participants: individual
      semi-structured interviews with care managers (29), nurses and care staff (70);
      telephone surveys with family members (73); staff reports of care approaches; and
      131 field note entries recorded by the person-centered care and environment
      facilitators. Data were interpreted inductively using content analysis, code
      building, theme development, and synthesis of findings. RESULTS: All data sources
      confirmed that, when adopted, the person-centered model increased the number and
      variety of opportunities for resident interaction, improved flexibility in care
      regimens, enhanced staff's attention to resident needs, reduced resident
      agitation, and improved their well-being. Barriers and enablers for the person
      centered model related to leadership, manager, staff and family appreciation of
      the model, staff's capacity, effective communication and team work among direct
      care staff, care service flexibility, and staff education on how to focus care on
      the person's well-being. CONCLUSIONS: Successful knowledge translation of the
      person-centered model starts with managerial leadership and support; it is
      sustained when staff are educated and assisted to apply the model, and, along
      with families, come to appreciate the benefits of flexible care services and
      teamwork in achieving resident well-being. The Australian New Zealand Clinical
      Trials Registry number is ACTRN 12608000095369.

PMID- 26307246
TI  - Network fingerprint: a knowledge-based characterization of biomedical networks.
AB  - It can be difficult for biomedical researchers to understand complex molecular
      networks due to their unfamiliarity with the mathematical concepts employed. To
      represent molecular networks with clear meanings and familiar forms for
      biomedical researchers, we introduce a knowledge-based computational framework to
      decipher biomedical networks by making systematic comparisons to well-studied
      "basic networks". A biomedical network is characterized as a spectrum-like vector
      called "network fingerprint", which contains similarities to basic networks. This
      knowledge-based multidimensional characterization provides a more intuitive way
      to decipher molecular networks, especially for large-scale network comparisons
      and clustering analyses. As an example, we extracted network fingerprints of 44
      disease networks in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database.
      The comparisons among the network fingerprints of disease networks revealed
      informative disease-disease and disease-signaling pathway associations,
      illustrating that the network fingerprinting framework will lead to new
      approaches for better understanding of biomedical networks. 

PMID- 26307247
TI  - Single tumor imaging with multiple antibodies targeting different antigens.
AB  - Antibodies are important drugs for treating cancer and there is strong rationale
      for using multiple antibodies to improve outcomes. We labeled two breast cancer
      binding antibodies, anti-ErbB2 and anti-EpCAM, with infrared fluorescence dyes of
      different wavelengths and determined their in vivo distribution in a breast
      cancer xenograft model using a near-infrared (NIR) fluorescence imaging system.
      Our data show that these two antibodies can be readily assessed simultaneously in
      mouse xenograft model. This will help guide design of dosing strategies for
      multiple antibodies and identify potential interaction that could affect
      pharmacokinetics and possible side effects. 

PMID- 26307248
TI  - ARF-TSS: an alternative method for identification of transcription start site in
      bacteria.
AB  - Current methods for identifying transcription start sites (TSSs) of specific
      genes in bacteria usually require adaptors or radioactive labeling. These
      approaches can be technically demanding and environmentally unfriendly. Here we
      present a method for identifying TSS called ARF-TSS, which is based on cDNA
      generation, circularization, PCR amplification, and DNA sequencing to determine
      the 5'-end of transcripts, thus circumventing the need for adaptors and
      radioactive labeling. We validated the method using the gene lasI from the
      bacterial pathogen Pseudomonas aeruginosa. Our results show that ARF-TSS could be
      a good alternative to traditional methods for bacterial TSS analysis. 

PMID- 26307249
TI  - Efficient and selective isotopic labeling of hemes to facilitate the study of
      multiheme proteins.
AB  - Specific isotopic labeling of hemes provides a unique opportunity to characterize
      the structure and function of heme-proteins. Unfortunately, current methods do
      not allow efficient labeling in high yields of multiheme cytochromes c, which are
      of great biotechnological interest. Here, a method for production of recombinant
      multiheme cytochromes c in Escherichia coli with isotopically labeled hemes is
      reported. A small tetraheme cytochrome of 12 kDa from Shewanella oneidensis MR-1
      was used to demonstrate the method, achieving a production of 4 mg pure protein
      per liter. This method achieves, in a single step, efficient expression and
      incorporation of hemes isotopically labeled in specific atom positions adequate
      for spectroscopic characterization of these complex heme proteins. It is,
      furthermore, of general application to heme proteins, opening new possibilities
      for the characterization of this important class of proteins. 

PMID- 26307251
TI  - Phosphorothioate-based DNA recombination: an enzyme-free method for the
      combinatorial assembly of multiple DNA fragments.
AB  - Rational guided generation of protein chimeras has developed into an attractive
      approach in protein engineering for tailoring catalytic and biophysical
      properties of enzymes. Combinatorial recombination of structural elements or
      whole protein domains is still technically challenging due to sequence dependent
      biases diminishing the overall quality of resulting chimeric libraries. Since
      methods for generating such libraries are often limited by a low frequency of
      crossover points and suffer from challenges in handling, we developed the
      phosphorothioate-based DNA recombination method (PTRec). PTRec is an enzyme-free
      method and only requires a short stretch of four amino acids that is identical
      among the proteins to be recombined in order to define a single crossover point.
      In a PTRec-generated chimeric library that shuffled five domains of phytase using
      genes from three different species, 88% of 42 randomly picked and sequenced genes
      were efficiently recombined. Furthermore, PTRec is a technically simple, fast,
      and reliable method that can be used for domain- and exon-shuffling or
      recombination of DNA fragments in general. 

PMID- 26307250
TI  - Microdissection of spatially identified single nuclei in a solid tumor for single
      cell whole genome sequencing.
AB  - The relative spatial distribution of cells in a solid tumor contributes to
      development of malignancy, yet the details of this process remain poorly
      understood. To elucidate these mechanisms, the ability to extract and analyze the
      entire DNA content of individual cells whose precise location in the tumor is
      known is required, yet such methodology has not yet been described. Here we
      detail a procedure to directly extract complete individual nuclei from fixed
      frozen tissue sections using through-focus analysis coupled with laser
      microdissection, followed by whole genome amplification. We show that this
      technique is suitable for routine evaluation of genomic variation such as SNP
      analyses of the specifically selected nuclei. Our method should provide a means
      for whole genome variation studies of single cells from spatially defined
      positions within tumor tissues. 

PMID- 26307252
TI  - Tools to discriminate between targets of CK2 vs PLK2/PLK3 acidophilic kinases.
AB  - While the great majority of Ser/Thr protein kinases are basophilic or proline
      directed, a tiny minority is acidophilic. The most striking example of such
      "acidophilic" kinases is CK2, whose sites are specified by numerous acidic
      residues surrounding the target one. However PLK2 and PLK3 kinases recognize an
      acidic consensus similar to CK2 when tested on peptide libraries. Here we
      describe optimal buffer conditions for PLK2 and 3 kinase activity assays and
      tools such as using GTP as a phosphate donor and the specific inhibitors CX-4945
      and BI 2536, useful to discriminate between acidic phosphosites generated either
      by CK2 or by PLK2/PLK3. 

PMID- 26307253
TI  - Common benzothiazole and benzoxazole fluorescent DNA intercalators for studying
      Alzheimer Abeta1-42 and prion amyloid peptides.
AB  - Amyloids are fibrillar protein aggregates associated with a number of
      neurodegenerative pathologies including Alzheimer and Creutzfeldt-Jakob disease.
      The study of amyloids is usually based on fluorescence with the dye thioflavin-T.
      Although a number of amyloid binding compounds have been synthesized, many are
      nonfluorescent or not readily available for research use. Here we report on a
      class of commercial benzothiazole/benzoxazole containing fluorescent DNA
      intercalators from Invitrogen that possess the ability to bind amyloid Abeta1-42
      peptide and hamster prion. These dyes fluoresce from 500-750 nm and are available
      as dimers or monomers. We demonstrate that these dyes can be used as acceptors
      for thioflavin-T fluorescence resonance energy transfer as well as reporter
      groups for binding studies with Congo red and chrysamine G. As more potential
      therapeutic compounds for these diseases are generated, there is a need for
      simple and inexpensive methods to monitor their interactions with amyloids. The
      fluorescent dyes reported here are readily available and can be used as tools for
      biochemical studies of amyloid structures and in vitro screening of potential
      therapeutics. 

PMID- 26307254
TI  - Rapid non-invasive genotyping of reporter transgenic mammals.
AB  - Here we describe a non-invasive method for rapid and highly reproducible
      genotyping of transgenic mammals with ubiquitous expression of fluorophore
      reporters. Hair samples from transgenic mice and pigs with systemic expression of
      the fluorophore reporter Venus were analyzed with a fluorescence microscope in
      few minutes. The hair samples can be preserved for long-term storage at ambient
      temperature conditions. This non-invasive method is useful for genotyping of
      transgenic large animals and contributes to animal welfare by reducing stress and
      discomfort of the animals during sample collection. 

PMID- 26307255
TI  - Generation of genetic constructs that simultaneously express several shRNAs.
AB  - RNAi has potential as an antiviral gene therapy strategy. Cassette constructs
      simultaneously expressing several siRNAs could prove to be the most efficient
      technique in developing gene therapy approaches for highly mutable viruses such
      as HIV-1. Here we describe a rapid and cost-saving protocol to generate cassettes
      that simultaneously express three siRNAs for repression of HIV-1 and CCR5
      transcripts. siRNA biological activity was tested in a non-viral system, and
      exhibited both efficiency and specificity. Our results suggest this protocol can
      be used to rapidly generate cassette constructs for antiviral gene therapy
      applications. 

PMID- 26307256
TI  - Transformation of diatom Phaeodactylum tricornutum by electroporation and
      establishment of inducible selection marker.
AB  - Diatoms are important primary producers in the marine ecosystem. Currently it is
      difficult to genetically transform diatoms due to the technical limitations of
      existing methods. The promoter/terminator of the nitrate reductase gene of the
      model diatom Phaeodactylum tricornutum was cloned and used to drive
      chloramphenicol acetyltransferase (CAT) reporter gene expression. The construct
      was transferred by electroporation into P. tricornutum grown in medium lacking
      silicon. CAT expression was induced in transformed diatoms in the presence of
      nitrate, enabling growth in selective medium, and was repressed when ammonium was
      the only nitrogen source. Expression of CAT transcript and protein were
      demonstrated by RT-PCR and Western blot analysis, respectively. Our study is the
      first to report a successful genetic transformation of diatom by electroporation
      in an economical and efficient manner and provides a tightly regulated inducible
      gene expression system for diatom. 

PMID- 26307257
TI  - PCR-based screening of targeted mutants for the fast and simultaneous
      identification of bacterial virulence factors.
AB  - Understanding the strategies used by pathogens to infect, survive, and
      proliferate in their hosts requires the identification of virulence factors. We
      developed PCR-based screening of targeted mutants to facilitate quick,
      simultaneous detection of multiple novel bacterial virulence genes. Based on
      direct PCR screening of pooled targeted mutants, this approach provides a fast
      and sensitive measure of virulence attenuation while significantly reducing the
      number of animals and time required. We demonstrate that the careful design of
      gene-specific primers allows the direct relative quantification of mixed mutants
      in infected mouse organs. Indeed, we show that the band intensity of the PCR
      product is directly related to the quantity of the corresponding strain in a pool
      of mutants. We applied the PCR-based screening of targeted mutants to the murine
      model of listeriosis and revealed new genes required for full pathogenicity of
      Listeria monocytogenes, a facultative human intracellular pathogen. PCR-based
      screening is a simple, useful, and fast technique to test pools of targeted
      bacterial mutants in vivo, without the requirements for a rigorous purification
      step, complicated PCR set-up, or special equipment. This approach can be adapted
      to other bacterial systems, constituting a significant advance in the field of
      infection biology. 

PMID- 26307258
TI  - Whole-mount imaging of the mouse hindlimb vasculature using the lipophilic
      carbocyanine dye DiI.
AB  - The availability of transgenic disease backgrounds and the accessibility of
      molecular research reagents have contributed to make the mouse ischemic hindlimb
      the model of choice for many studies of angiogenesis, and to investigate new
      treatments for peripheral artery disease. A limitation of these models involves
      our inability to easily visualize the regenerated vascular architecture.
      Approaches such as micro-computed tomography and micro-angiography are expensive,
      technically demanding and not available to many laboratories. Here we describe a
      rapid and inexpensive adaptation of a vascular staining procedure for precise
      imaging of the mouse hindlimb vasculature. We introduced two technical
      modifications and an analytical extension to the original method including (i)
      pre-skinning of the muscle prior to fixation that preserves tissue integrity,
      (ii) mild pressure-desiccation subsequent to fixing that enhances resolution and
      image penetration, and (iii) reconstruction of confocal data into 3D images. The
      procedure provides resolution that is equivalent or superior to other approaches
      at a fraction of the cost, time and technology required. 

PMID- 26307259
TI  - Red/ET recombination with chimeric oligonucleotides allows rapid generation of
      BAC transgenes harboring full-length or truncated huntingtin cDNA.
AB  - Huntington's disease (HD) is a fatal neurodegenerative disorder that is caused by
      a CAG repeat expansion encoding a polyglutamine tract in the huntingtin (htt)
      gene. None of the existing HD mouse models recapitulate the exact disease
      symptoms and course as it is seen in humans and the generation of further HD
      disease models is challenging because of the size and complexity of the htt gene
      locus. Starting from a single substrate plasmid harboring human htt cDNA
      comprising 98 glutamine (Q) residues, we applied Red/ET recombination to generate
      four BDNF-BAC transgenes harboring full-length or truncated (N171) htt cDNA
      comprising 98 or 15 Q residues. BDNF (brain-derived neurotrophic factor) is
      expressed in the cortical neurons projecting to the striatal medium spiny
      neurons, and was used to direct htt transgene expression to investigate the
      contribution of these cell types to HD. 

PMID- 26307260
TI  - High-efficiency transfection of suspension cell lines.
AB  - Transfection of suspension cells has proven to be very difficult using
      conventional methods. Here, we present a simple and time-saving new transfection
      protocol wherein cell culture plates coated with chicken egg white are seeded
      with suspension cells prior to transfection. Our results demonstrate that
      coupling egg white coatings with commercially available transfection reagents
      leads to high transfection efficiency with suspension cell lines including canine
      mastocytoma C2 and the human myeloid cell line HL-60. This new approach, which
      should prove applicable to a wide range of cell lines, solves a crucial problem
      for researchers working with suspension cells. 

PMID- 26307261
TI  - Using dot blot with immunochemical detection to evaluate global changes in SUMO
      2/3 conjugation.
AB  - Small ubiquitin-related modifier-2/3 (SUMO-2/3) is a member of the ubiquitin-like
      (Ubl) protein family. Conjugation of SUMO-2/3 to target proteins is influenced by
      various stress conditions and chemical inhibitors. SUMO-2/3 conjugation may serve
      as a neuroprotective mechanism and may play a role in protein quality control. A
      method for screening global changes in SUMO-2/3 conjugation would facilitate
      further research of SUMO-2/3 cellular function. Here we show that dot blot with
      immunochemical detection allows evaluation of changes in global cellular SUMO-2/3
      conjugation and offers an alternative to more laborious Western blot analysis.
      The method is based on a change of SUMO-2/3 signal intensity upon its
      conjugation. The dot blot analysis presented here is a time-saving method that
      enables screening of large numbers of samples and easy statistical evaluation of
      the results. 

PMID- 26307262
TI  - Photostability and ex-vivo permeation studies on diclofenac in topical niosomal
      formulations.
AB  - Photostability studies were performed on topical formulations containing
      diclofenac (DC). Niosomal gels were designed as photostabilization systems and
      ascorbic acid was also added to the new topical formulations because of its
      antioxidant property. Photodegradation tests were applied on commercial
      formulations containing DC and novel prepared gels, according to the ICH rules.
      The experiments were monitored by spectrophotometry and the data processed by
      multivariate curve resolution analysis to estimate the spectra and concentration
      profiles of evolved components. Characterization of niosomes was evaluated by
      size and distribution measurement, morphological analysis and encapsulation
      efficiency. Permeation experiments were performed across rabbit ear skin up to 24
      h. Photodegradation rate of DC was found very fast in commercial formulation,
      with a residual content of 90% after only 4.38 min under a radiant exposure of
      450 W/m(2). Photostability resulted increased significantly when the drug was
      entrapped in niosomal systems. The best results were obtained by reaching a 10%
      degradation after 50.00 min of light exposure after incorporation of DC in
      niosomes in presence of 5% ascorbic acid. Moreover, niosomal gel also influenced
      the permeation capability of DC by enhancing the transdermal delivery of the
      drug. The cumulative dose permeated of DC from niosomal gel was about three times
      that obtained with the commercial gel.

PMID- 26307263
TI  - Incorporating small molecules or biologics into nanofibers for optimized drug
      release: A review.
AB  - Over the past several decades, the formulation of novel nanofiber-based drug
      delivery systems focusing on specific delivery purposes has been investigated
      worldwide with a continuous level of interest. The unique structure and
      properties of nanoscale fibrous systems, such as their high specific-area-to
      volume ratio and high porosity and the possibility of controlling their
      crystalline-amorphous phase transitions, make them a desirable formulation
      pathway to satisfy the needs of recent pharmaceutical development. Fibrous
      delivery systems can facilitate the accelerated dissolution and increased
      solubility of small molecules and can also be useful in controlling drug delivery
      over time (for local or systemic drug administration). In the latter case, the
      release periods can be tuned over a wide range (from hours to weeks), e.g., by
      adjusting the fiber diameter and selecting the appropriate polymers. The
      solubility of the polymer, the fiber diameter and the fiber structure are the
      primary parameters affecting drug release. In addition to immediate and sustained
      release, other release profiles, such as biphasic release, can also be achieved.
      Chemical conjugation and surface functionalization offer further possibilities
      for the control of drug release. In the case of small molecules, developments
      focus mostly on overcoming the unfavorable physicochemical nature of the active
      agents. By contrast, in the preparation of macromolecule-loaded nanofibers,
      maximizing the biological activity of the macromolecules presents the greatest
      challenge. The authors' intent is to provide a comprehensive overview of the key
      parameters of advanced drug delivery systems of this type. 

PMID- 26307264
TI  - Stability of fluorescent labels in PLGA polymeric nanoparticles: Quantum dots
      versus organic dyes.
AB  - Polymeric nanoparticles (NPs) are currently being investigated for various
      therapeutic, diagnostic and drug delivery applications. The study of their
      interactions and fate in biological systems is frequently performed via their
      fluorescent labeling and following them using fluorescent microscopy. Quantum
      dots are proposed as stable fluorescent label and compared to other organic dyes
      (Nile red and DiI) in terms of their entrapment, diffusion in different aqueous
      or lipophilic media and photostability. In vitro transfer to hydrophilic PBS
      solution showed that after 8h, 4.2+/-2.2, 15.5+/-2.0 and 0.9+/-0.02% was released
      from the QDs, NR and DiI nanoparticles, respectively. However, higher diffusion
      rates were observed in the lipophilic medium chain triglyceride and artificial
      sebum for all the dyes used. Fluorescent intensity of the three different markers
      was found to be stable over a period of 24h. Continuous illumination with laser
      beam using a confocal laser scanning microscopy indicated the superior stability
      of quantum dots compared to the other organic dyes. Skin permeation experiments
      have shown that QDs were the most representative marker for the polymeric
      nanoparticles skin penetration. 

PMID- 26307265
TI  - A qualitative study of factors influencing retention of doctors and nurses at
      rural healthcare facilities in Bangladesh.
AB  - BACKGROUND: Bangladesh is a highly populous country with three-quarters rural
      population. Pressing national shortages in health professionals has resulted in
      high vacancy rates in rural areas. These are compounded by excessive absenteeism
      and low retention among nurses and doctors posted to rural locations. This study
      attempts to ascertain reasons for providers' reluctance to work in rural and
      remote areas and to identify ways in which these barriers to appropriate staffing
      might be resolved. METHODS: This is a qualitative study based on in-depth
      interviews with healthcare providers (n = 15) and facility managers (n = 4)
      posted in rural areas, and key informant interviews with health policymakers at
      the national level (n = 2). Interview guides were written in English and
      translated and administered in Bengali. The collected data were re-translated and
      analyzed in English. Braun and Clarke's thematic analysis approach (data
      familiarization, coding, identifying and reviewing themes, and producing a final
      report) was used. RESULTS: Participants reported poor living conditions in rural
      areas (e.g., poor housing facilities and unsafe drinking water); overwhelming
      workloads with poor safety and insufficient equipment; and a lack of
      opportunities for career development, and skill enhancement. They reported
      insufficient wages and inadequate opportunities for private practice in rural
      areas. Managers described their lack of sufficient authority to undertake
      disciplinary measures for absenteeism. They also pointed at the lack of fairness
      in promotion practices of the providers. Policymakers acknowledged unavailability
      or insufficient allowances for rural postings. There is also a lack of national
      policy on rural retention. CONCLUSIONS: The findings revealed a complex interplay
      of factors influencing doctors' and nurses' availability in rural and remote
      public health facilities from the perspective of different players in the
      healthcare delivery system of Bangladesh. In addition, the study generated
      several possibilities for improvement, including increased allowances and
      incentives for rural posting; a transparent and fair promotion system for serving
      in rural areas; enhanced authority of the local managers for reducing worker
      absenteeism; and improved national policies on rural retention.

PMID- 26307266
TI  - Resveratrol via sirtuin-1 downregulates RE1-silencing transcription factor (REST)
      expression preventing PCB-95-induced neuronal cell death.
AB  - Resveratrol (3,5,4'-trihydroxystilbene) (RSV), a polyphenol widely present in
      plants, exerts a neuroprotective function in several neurological conditions; it
      is an activator of class III histone deacetylase sirtuin1 (SIRT1), a crucial
      regulator in the pathophysiology of neurodegenerative diseases. By contrast, the
      RE1-silencing transcription factor (REST) is involved in the neurotoxic effects
      following exposure to polychlorinated biphenyl (PCB) mixture A1254. The present
      study investigated the effects of RSV-induced activation of SIRT1 on REST
      expression in SH-SY5Y cells. Further, we investigated the possible relationship
      between the non-dioxin-like (NDL) PCB-95 and REST through SIRT1 to regulate
      neuronal death in rat cortical neurons. Our results revealed that RSV
      significantly decreased REST gene and protein levels in a dose- and time
      dependent manner. Interestingly, overexpression of SIRT1 reduced REST expression,
      whereas EX-527, an inhibitor of SIRT1, increased REST expression and blocked RSV
      induced REST downregulation. These results suggest that RSV downregulates REST
      through SIRT1. In addition, RSV enhanced activator protein 1 (AP-1) transcription
      factor c-Jun expression and its binding to the REST promoter gene. Indeed, c-Jun
      knockdown reverted RSV-induced REST downregulation. Intriguingly, in SH-SY5Y
      cells and rat cortical neurons the NDL PCB-95 induced necrotic cell death in a
      concentration-dependent manner by increasing REST mRNA and protein expression. In
      addition, SIRT1 knockdown blocked RSV-induced neuroprotection in rat cortical
      neurons treated with PCB-95. Collectively, these results indicate that RSV via
      SIRT1 activates c-Jun, thereby reducing REST expression in SH-SY5Y cells under
      physiological conditions and blocks PCB-95-induced neuronal cell death by
      activating the same SIRT1/c-Jun/REST pathway. 

PMID- 26307268
TI  - Bone scintigraphy predicts bisphosphonate-induced osteonecrosis of the jaw
      (BRONJ) in patients with metastatic castration-resistant prostate cancer (mCRPC).
AB  - OBJECTIVES: The aim of this study was to evaluate the role of bone scintigraphy
      (BS) in early prediction of clinically asymptomatic bisphosphonate (BP)-related
      osteonecrosis of the jaws (BRONJ) in patients with metastatic castration
      resistant prostate cancer (mCRPC). MATERIAL AND METHODS: BS of mCRPC patients
      treated with BP was evaluated for pathologic tracer uptake of the jaws in BS
      suspicious for BRONJ. Results were compared to development of clinically evident
      BRONJ. Sensitivity, specificity and predictive values of BS for the detection of
      BRONJ as well as time from beginning of BP therapy to pathologic tracer uptake in
      BS and time from pathologic tracer uptake in BS to clinically evident BRONJ were
      determined. RESULTS: Thirty BP-treated patients were included. Nine patients
      (30%) had pathologic BS lesions of the jaws. Six patients (20%) developed BRONJ.
      Sensitivity and specificity of BS for BRONJ prediction were 67 and 79%. Median
      time from the start of BP treatment to pathologic tracer uptake in BS was 28
      months (range 10-33) and from pathologic tracer uptake in BS to clinically
      evident BRONJ 6.5 months (range 2-19). Pathologic tracer uptake in BS was
      significantly more often observed in patients who developed BRONJ compared to
      patients who did not (p = 0.049; OR 7.6). CONCLUSIONS: Patients with pathologic
      tracer uptake in the jaws in BS significantly more often develop BRONJ. An
      unsuspicious BS is predictive for absence of BRONJ in the future. CLINICAL
      RELEVANCE: We conclude that when BS has been performed, it should not only be
      used to assess tumour stage and treatment response but also to check for
      pathologic tracer uptake in the jaws in BS to detect BRONJ at an early stage in
      mCRPC patients receiving bisphosphonates.

PMID- 26307270
TI  - Novel mode of 2-fold interpenetration observed in a primitive cubic network of
      formula [Ni(1,2-bis(4-pyridyl)acetylene)2(Cr2O7)]n.
AB  - A primitive cubic (pcu) network of formula [Ni(1,2-bis(4
      pyridyl)acetylene)2(Cr2O7)]n, , has been synthesised and found to exhibit a novel
      type of inclined 2-fold interpenetration and an isosteric heat of adsorption
      (Q(st)) of 30.5 kJ mol(-1) towards CO2 at zero loading. Q(st) is relatively high
      in the broad context but less than that observed in related hybrid
      ultramicroporous materials, a feature that can be understood after studying pore
      structure and molecular simulations of CO2 adsorption.

PMID- 26307267
TI  - Methamphetamine and HIV-Tat alter murine cardiac DNA methylation and gene
      expression.
AB  - This study addresses the individual and combined effects of HIV-1 and
      methamphetamine (N-methyl-1-phenylpropan-2-amine, METH) on cardiac dysfunction in
      a transgenic mouse model of HIV/AIDS. METH is abused epidemically and is
      frequently associated with acquisition of HIV-1 infection or AIDS. We employed
      microarrays to identify mRNA differences in cardiac left ventricle (LV) gene
      expression following METH administration (10d, 3mg/kg/d, subcutaneously) in
      C57Bl/6 wild-type littermates (WT) and Tat-expressing transgenic (TG) mice.
      Arrays identified 880 differentially expressed genes (expression fold change>1.5,
      p<0.05) following METH exposure, Tat expression, or both. Using pathway
      enrichment analysis, mRNAs encoding polypeptides for calcium signaling and
      contractility were altered in the LV samples. Correlative DNA methylation
      analysis revealed significant LV DNA methylation changes following METH exposure
      and Tat expression. By combining these data sets, 38 gene promoters (27 related
      to METH, 11 related to Tat) exhibited differences by both methods of analysis.
      Among those, only the promoter for CACNA1C that encodes L-type calcium channel
      Cav1.2 displayed DNA methylation changes concordant with its gene expression
      change. Quantitative PCR verified that Cav1.2 LV mRNA abundance doubled following
      METH. Correlative immunoblots specific for Cav1.2 revealed a 3.5-fold increase in
      protein abundance in METH LVs. Data implicate Cav1.2 in calcium dysregulation and
      hypercontractility in the murine LV exposed to METH. They suggest a pathogenetic
      role for METH exposure to promote LV dysfunction that outweighs Tat-induced
      effects. 

PMID- 26307269
TI  - Robot-assisted microwave thermoablation of liver tumors: a single-center
      experience.
AB  - PURPOSE: To evaluate and compare the needle placement accuracy, patient dose,
      procedural time, complication rate and ablation success of microwave
      thermoablation using a novel robotic guidance approach and a manual approach.
      METHODS: We performed a retrospective single-center evaluation of 64 microwave
      thermoablations of liver tumors in 46 patients (10 female, 36 male, mean age 66
      years) between June 2014 and February 2015. Thirty ablations were carried out
      with manual guidance, while 34 ablations were performed using robotic guidance. A
      6-week follow-up (ultrasound, computed tomography and MRI) was performed on all
      patients. RESULTS: The total procedure time and dose-length product were
      significantly reduced under robotic guidance (18.3 vs. 21.7 min, [Formula: see
      text]; 2216 vs. 2881 mGy[Formula: see text]cm, [Formula: see text]). The position
      of the percutaneous needle was more accurate using robotic guidance (needle
      deviation 1.6 vs. 3.3 mm, [Formula: see text]). There was no significant
      difference between both groups regarding the complication rate and the ablation
      success. CONCLUSION: Robotic assistance for liver tumor ablation reduces patient
      dose and allows for fast positioning of the microwave applicator with high
      accuracy. The complication rate and ablation success of percutaneous microwave
      thermoablation of malignant liver tumors using either CT fluoroscopy or robotic
      guidance for needle positioning showed no significant differences in the 6-week
      follow-up.

PMID- 26307271
TI  - Fatal systemic infection following an outpatient hysteroscopic diagnosis of a
      chronic pyometra: a case report and survey of practice.

PMID- 26307272
TI  - Our talent at the top is still going to waste.
AB  - Waste in the health service is nothing new, with stories usually focusing on
      supplies and procurement. But as Nursing Standard reveals this week, there is a
      serious ongoing issue with the profession's most senior staff. Too many of them
      are struggling in their roles and are either being removed from their posts or
      are walking away having had enough. The wasted talent is nothing short of a
      scandal. 

PMID- 26307273
TI  - High turnover of nursing directors is damaging to trusts' performance.
AB  - Nearly one fifth of nursing directors in England have been in the post for a year
      or less, exclusive research by Nursing Standard reveals. 

PMID- 26307274
TI  - Artist chosen for Cavell memorial.
AB  - A new memorial to first world war nurse Edith Cavell sparked a scramble to win
      the right to carve her name on a stone at Norwich Cathedral where she is buried. 

PMID- 26307275
TI  - Anger over lack of parking at Glasgow's super hospital.
AB  - Nurses working at the UK's largest hospital are paying up to L8.50 a day to rent
      out private driveways because of a shortage of parking spaces. 

PMID- 26307276
TI  - Give UK nursing bigger global voice by rejoining ICN, college is urged.
AB  - The next chief executive of the International Council of Nurses should encourage
      the RCN to rejoin the organisation and ensure the UK has a greater say on nursing
      at a global level, a former college president believes. 

PMID- 26307277
TI  - Safety of patients to be scrutinised by commons group.
AB  - A cross-party group of MPs has been assembled by the Patients Association to
      address issues compromising patient safety. 

PMID- 26307278
TI  - Immigration rules could hit hard.
AB  - Directors of nursing are warning the government that its policy of not allowing
      some foreign nurses to work in the UK if they earn less than L35,000 will create
      serious staffing shortages. 

PMID- 26307279
TI  - Senior lecturer set to confer first paediatric diplomas on trip to Zambia.
AB  - An award-winning nurse lecturer is preparing to travel to Africa armed with
      certificates to celebrate the success of her university's inaugural paediatric
      nursing course. 

PMID- 26307281
TI  - Staff gain support on e-cigarette use.
AB  - An expert independent evidence review for Public Health England states that e
      cigarettes are 95% less harmful than tobacco and using them could be a game
      changer in helping people to stop smoking. 

PMID- 26307282
TI  - Older rural population needs a flexible nursing workforce.
AB  - A 'radical shift in resources' is required to meet the needs of older people in
      remote and rural areas, according to a report published by the RCN with support
      from Age Scotland. 

PMID- 26307283
TI  - E-learning modules will help cut classroom-based training.
AB  - A health organisation has turned to technology to get staff out of the classroom
      and back on the front line. 

PMID- 26307284
TI  - Patients know nurses are less likely to prescribe antibiotics, study finds.
AB  - Fewer patients expect to be prescribed antibiotics when they see a nurse than
      when they are seen by a doctor, a study of prescribing habits has shown. 

PMID- 26307285
TI  - Directors head for the exit as lack of support and pressures rack up.
AB  - More than 60% of nursing directors in England have been in post for three years
      or less, exclusive research by Nursing Standard reveals. 

PMID- 26307291
TI  - Trust trials new model of testing competency.

PMID- 26307292
TI  - Challenging people's ideas.

PMID- 26307293
TI  - Consultant role bridges the gap.

PMID- 26307302
TI  - Downs Side Up.
AB  - Downs Side Up is a website run by Hayley Goleniowska, a mother of two girls, one
      of whom - Natty - has Down's syndrome. 

PMID- 26307304
TI  - The best of the week's health-related TV and radio.

PMID- 26307305
TI  - RxmindMe Prescription/Medicine Reminder and Pill Tracker.
AB  - Tablets, capsules, injections, inhalers... it never fails to surprise me how many
      medications some of our patients have to take every day, just to stay healthy. 

PMID- 26307306
TI  - It is unclear how the NHS defines 'fluent' - or how it will find staff.
AB  - Asking staff to speak fluent English is well and good, but how will 'fluent' be
      defined? I have worked alongside colleagues for whom English is their first and
      only language, yet their manner of speech is appalling. 

PMID- 26307307
TI  - Public health blow is just an NHS funding cut under another name.
AB  - The proposed L200 million cut to the public health grant (news, August 19)
      highlights the deceit of the chancellor regarding protecting NHS funding. 

PMID- 26307308
TI  - Nurses and their patients must be talking the same language.
AB  - I agree with the Nursing Standard readers panel (August 19) that nursing staff
      who work directly with the public should be able to speak English fluently. 

PMID- 26307309
TI  - Communication with patients is vital if we are to help them.
AB  - The readers panel debate on nurses' ability to communicate effectively prompted
      me to reflect on a recent agency shift during which I cared for a patient who was
      deaf. 

PMID- 26307310
TI  - If reflection is an NMC requirement, we should give staff the time to do it.
AB  - The new Nursing and Midwifery Council revalidation process places a great deal of
      emphasis on reflection (analysis, July 29), which is an important element of
      being a holistic and effective practitioner. 

PMID- 26307311
TI  - Nurses need proper breaks to change unhealthy eating habits.
AB  - A national newspaper carried an interview recently with nurse Carole Crocker, who
      had lost weight after being challenged by a patient. 

PMID- 26307312
TI  - The battle against dementia is about more than finding a cure.
AB  - New research shows international dementia prevalence is not rising as quickly as
      believed, as highlighted in the UK two years ago by professor of public health
      medicine Carol Brayne. 

PMID- 26307314
TI  - Scheme aims to ensure students become competent practitioners.
AB  - Thank you for publishing my article on the programme that Central Manchester NHS
      Foundation Trust has developed to provide additional preparatory support to
      enable third-year nursing and midwifery students to become competent
      practitioners, at the point of registration (careers, August 19). However, there
      were some changes made during editing that I would like to correct. 

PMID- 26307316
TI  - Recognition and management of febrile convulsion in children.
AB  - Febrile convulsion is characterised by convulsion associated with fever in an
      infant or child aged between six months and six years. The febrile illness
      causing the convulsion should not be secondary to an intracranial infection
      (meningitis or encephalitis) or acute electrolyte imbalance. Most cases of
      febrile convulsion are short lived and self-terminating. However, a few cases of
      prolonged febrile convulsion may need anticonvulsant medication to stop the
      seizure. Management is mainly symptomatic, although anticonvulsants may have a
      role in a small number of children with complex or recurrent febrile convulsion.
      Referral to paediatric neurologists may be necessary in cases of complex or
      recurrent febrile convulsion, or in those where a pre-existing neurological
      disorder exists. One third of children will develop a further febrile convulsion
      during subsequent febrile illness. Nurses have a vital role in managing children
      with febrile convulsion, educating parents about the condition and dispelling
      myths. This article outlines the presentation, management, investigations and
      prognosis for febrile convulsion, indicating how nurses working in different
      clinical areas can help to manage this common childhood condition. 

PMID- 26307317
TI  - Comparison of family planning in Cuba and Ireland.
AB  - Family planning gives individuals and couples control and choice over the number
      of children they have and the timing of their births. Developments in
      reproductive health have resulted in major changes in the options for family
      planning, providing more choice and control over fertility. This article explores
      reproductive health in the Republic of Cuba and the Republic of Ireland, with a
      focus on contraceptive use and termination of pregnancy as methods of family
      planning. The predominant religion in both countries is Catholicism, which
      promotes the right to life of the unborn child. The two countries have adopted
      different approaches to the availability of both contraception and termination of
      pregnancy. Cuba has offered free access to contraception and termination of
      pregnancy since the 1960s to reduce maternal mortality. In Ireland, contraception
      was not widely available until 1995 and termination of pregnancy is available
      only in extremely limited circumstances. 

PMID- 26307318
TI  - Using systematic reviews to inform nursing practice.
AB  - Health care is constantly being reformed to improve the safety and quality of
      services, and nurses are integral to the provision of this safety and quality. As
      a result of concerns raised by recent high-profile care failings, there is an
      expectation that the nursing profession should be able to meet the changing
      demands of an increasingly complex healthcare environment, based on the best
      available evidence. This article describes the use of systematic literature
      reviews to recognise appropriate evidence and develop guidelines to inform
      nursing practice, thereby enabling safe, high quality nursing care. It uses an
      example from the literature to illustrate the process of systematic review. 

PMID- 26307319
TI  - Agitation.
AB  - The CPD article about caring for older people experiencing agitation is relevant
      to my practice. I work on an acute oncology assessment ward, which provides rapid
      assessment and care for acutely unwell patients. 

PMID- 26307321
TI  - Opportunity to make a difference.
AB  - Clinical electives in developing countries can improve health through education,
      organisational support, advocacy, delivery of health services, and support to
      peers who are often working under great pressure. 

PMID- 26307320
TI  - Beyond the expected.
AB  - Joan Pons Laplana's nursing career has not been linear, which perhaps befits a
      man who believes in 'horizontal power' and challenges hierarchy. 

PMID- 26307323
TI  - Managing emotions at work.
AB  - Every nurse is taught during training to put their emotions to one side when
      making decisions about patient care. Objectivity enables nurses to make evidence
      based decisions. However, remaining objective is not easy. 

PMID- 26307324
TI  - Student life - Fly on the wall approach.
AB  - Imagine your grandmother was in hospital. How would you expect her to be treated?
      Would the nurse or doctor smile and ask her how she's feeling? Imagine what you
      would see if you were a fly on the wall. 

PMID- 26307326
TI  - Neural development: a complex competition for spines.

PMID- 26307325
TI  - Timetable for oral prevention in childhood-a current opinion.
AB  - Dental caries in young children remains a public health problem particularly for
      children whose families are socioeconomically deprived. A child's first dental
      visit should be at approximately 12 months of age and this should facilitate the
      provision of anticipatory guidance concerning oral health and dental development
      to the child's parents/guardians. Compliance with dietary advice is of key
      importance and motivational interviewing shows promise in relation to parents
      adopting good oral health practices for their children. Twice daily toothbrushing
      using toothpaste that contains in the range of 1000- 1500ppmF is a most important
      preventive measure. It is important to use a minimal amount of toothpaste, insure
      that it is not swallowed, have parental or adult supervision during toothbrushing
      and avoid rinsing with water following brushing with toothpaste. The professional
      application of topical fluoride varnish twice yearly is a proven caries
      preventative measure. The application of pit and fissure sealants to teeth with
      deep pits and fissures is recommended. 

PMID- 26307327
TI  - Two-step complete polarization logic Bell-state analysis.
AB  - The Bell state plays a significant role in the fundamental tests of quantum
      mechanics, such as the nonlocality of the quantum world. The Bell-state analysis
      is of vice importance in quantum communication. Existing Bell-state analysis
      protocols usually focus on the Bell-state encoding in the physical qubit
      directly. In this paper, we will describe an alternative approach to realize the
      near complete logic Bell-state analysis for the polarized concatenated
      Greenberger-Horne-Zeilinger (C-GHZ) state with two logic qubits. We show that the
      logic Bell-state can be distinguished in two steps with the help of the parity
      check measurement (PCM) constructed by the cross-Kerr nonlinearity. This approach
      can be also used to distinguish arbitrary C-GHZ state with N logic qubits. As
      both the recent theoretical and experiment work showed that the C-GHZ state has
      its robust feature in practical noisy environment, this protocol may be useful in
      future long-distance quantum communication based on the logic-qubit entanglement.

PMID- 26307328
TI  - Pharmacokinetics, pharmacodynamics and clinical efficacy of pertuzumab in breast
      cancer therapy.
AB  - INTRODUCTION: Pertuzumab is a recombinant, humanized monoclonal antibody that
      binds to the dimerization domain of human epidermal growth factor receptor 2
      (HER2), inhibiting the heterodimerization of HER2 with other HER receptors. It
      has shown synergy with trastuzumab in preclinical studies, and has led to a
      significant prolongation of progression-free and overall survival compared with
      placebo when added to trastuzumab and docetaxel for the first-line treatment of
      HER2-positive metastatic breast cancer (BC). AREAS COVERED: The HER family of
      receptors and their pathways, pertuzumab pharmacodynamics and preclinical
      activity, results from the main clinical trials, new drug combinations being
      developed, and predictors of response are discussed. EXPERT OPINION: Pertuzumab
      represents an important anti-HER2 agent that differs from, but is synergistic
      with, trastuzumab. It is already a standard of care in the first-line treatment
      of HER2-positive metastatic BC, and studies are ongoing to define its role in the
      adjuvant setting. It is now imperative to identify which tumors need dual HER2
      targeting and to study the activity of pertuzumab in combination with other HER
      targeted agents, including anti-HER1, -HER3 or -HER4, which could also prove
      useful in HER2-normal cancers. Potential competitors are anti-HER3 antibodies and
      bi- or tri-specific antibodies. Development in combination with phosphoinositide
      3-kinase inhibitors or with anti PD-L1 is warranted.

PMID- 26307329
TI  - Neuromodulation in the Treatment of Epilepsy.
AB  - OPINION STATEMENT: Neuromodulation devices are used in the treatment of medically
      refractory epilepsy. This has been defined as epilepsy with persistent seizures
      despite adequate trials of at least two anti-epileptic drugs (AEDs). In most
      cases of medically refractory partial epilepsy, the first choice of treatment is
      resective surgery if the seizure focus can be definitively localized and if
      surgery can be safely performed without causing intolerable neurologic deficits.
      Patients with medically refractory epilepsy who are not candidates for
      potentially curative surgery may benefit from the implantation of a
      neuromodulation device. While most of these devices require surgical
      implantation, they provide a significant added seizure reduction without typical
      medication side effects. Furthermore, the efficacy of these devices continues to
      improve over years. There are currently no head-to-head trials comparing the
      different neuromodulation devices but efficacy appears to be roughly similar. The
      choice of device therefore depends on the type of epilepsy, whether the seizure
      focus can be identified, and other clinical factors. Vagal Nerve Stimulation
      (VNS) does not require identification of the seizure focus and also carries an
      FDA indication for depression. While in the United States VNS is only approved
      for use in partial epilepsy, it is commonly used off-label to treat generalized
      seizures as well. VNS delivers stimulation on a scheduled basis, in response to
      patient activation, or in response to heart rate increases serving as a proxy for
      seizures. Responsive Neurostimulation (RNS) requires the identification of up to
      two seizure foci and delivers stimulation only in response to the detection of
      epileptiform activity. While it requires intracranial placement of electrodes, it
      allows for long-term monitoring of electrographic seizures and may be effective
      where VNS has not produced an optimal response. Deep brain stimulation of the
      anterior nucleus of the thalamus is not FDA approved at this time but is
      available in Europe and many other parts of the world. While it also carries an
      indication only for partial epilepsy, it does not require identification of the
      seizure focus and may be particularly helpful for temporal lobe epilepsy. It also
      appears effective in cases where VNS has not been sufficiently helpful. The
      Trigeminal Nerve Stimulation (TNS) system is another treatment modality which is
      not yet FDA approved but is available in Europe and other countries. Its
      mechanism of action is similar to the VNS system and it also appears to have anti
      depression effects in addition to anti-epileptic benefits. However, the most
      compelling feature of TNS is that it is not implanted but rather applied to the
      skin with transdermal electrodes, typically at night.

PMID- 26307330
TI  - Automatized Patient-Specific Methodology for Numerical Determination of
      Biomechanical Corneal Response.
AB  - This work presents a novel methodology for building a three-dimensional patient
      specific eyeball model suitable for performing a fully automatic finite element
      (FE) analysis of the corneal biomechanics. The reconstruction algorithm fits and
      smooths the patient's corneal surfaces obtained in clinic with corneal
      topographers and creates an FE mesh for the simulation. The patient's corneal
      elevation and pachymetry data is kept where available, to account for all corneal
      geometric features (central corneal thickness-CCT and curvature). Subsequently,
      an iterative free-stress algorithm including a fiber's pull-back is applied to
      incorporate the pre-stress field to the model. A convergence analysis of the mesh
      and a sensitivity analysis of the parameters involved in the numerical response
      is also addressed to determine the most influential features of the FE model. As
      a final step, the methodology is applied on the simulation of a general non
      commercial non-contact tonometry diagnostic test over a large set of 130 patients
      53 healthy, 63 keratoconic (KTC) and 14 post-LASIK surgery eyes. Results show the
      influence of the CCT, intraocular pressure (IOP) and fibers (87%) on the
      numerical corneal displacement (U(Num)) the good agreement of the U(Num) with
      clinical results, and the importance of considering the corneal pre-stress in the
      FE analysis. The potential and flexibility of the methodology can help improve
      understanding of the eye biomechanics, to help to plan surgeries, or to interpret
      the results of new diagnosis tools (i.e., non-contact tonometers).

PMID- 26307331
TI  - Patient-Specific Biomechanical Modeling of Bone Strength Using Statistically
      Derived Fabric Tensors.
AB  - Low trauma fractures are amongst the most frequently encountered problems in the
      clinical assessment and treatment of bones, with dramatic health consequences for
      individuals and high financial costs for health systems. Consequently,
      significant research efforts have been dedicated to the development of accurate
      computational models of bone biomechanics and strength. However, the estimation
      of the fabric tensors, which describe the microarchitecture of the bone, has
      proven to be challenging using in vivo imaging. On the other hand, existing
      research has shown that isotropic models do not produce accurate predictions of
      stress states within the bone, as the material properties of the trabecular bone
      are anisotropic. In this paper, we present the first biomechanical study that
      uses statistically-derived fabric tensors for the estimation of bone strength in
      order to obtain patient-specific results. We integrate a statistical predictive
      model of trabecular bone microarchitecture previously constructed from a sample
      of ex vivo micro-CT datasets within a biomechanical simulation workflow. We
      assess the accuracy and flexibility of the statistical approach by estimating
      fracture load for two different databases and bone sites, i.e., for the femur and
      the T12 vertebra. The results obtained demonstrate good agreement between the
      statistically-driven and micro-CT-based estimates, with concordance coefficients
      of 98.6 and 95.5% for the femur and vertebra datasets, respectively. 

PMID- 26307332
TI  - Cyclic Stretch and Perfusion Bioreactor for Conditioning Large Diameter
      Engineered Tissue Tubes.
AB  - A cyclic stretch and perfusion bioreactor was designed to culture large diameter
      engineered tissue tubes for heart valve applications. In this bioreactor, tubular
      tissues consisting of dermal fibroblasts in a sacrificial fibrin gel scaffold
      were placed over porated latex support sleeves and mounted in a custom
      bioreactor. Pulsatile flow of culture medium into the system resulted in cyclic
      stretching as well as ablumenal, lumenal, and transmural flow (perfusion). In
      this study, lumenal remodeling, composition, and mechanical strength and
      stiffness were compared for tissues cyclically stretched in this bioreactor on
      either the porated latex sleeves or solid latex sleeves, which did not permit
      lumenal or transmural flow. Tissues cyclically stretched on porated sleeves had
      regions of increased lumenal remodeling and cellularity that were localized to
      the columns of pores in the latex sleeve. A CFD model was developed with COMSOL
      Multiphysics((r)) to predict flow of culture medium in and around the tissue, and
      the predictions suggest that the enhanced lumenal remodeling was likely a result
      of elevated shear stresses and transmural velocity in these regions. This work
      highlights the beneficial effects of increased nutrient transport and flow
      stimulation for accelerating in vitro tissue remodeling. 

PMID- 26307333
TI  - Early unclamping might reduce the risk of renal artery pseudoaneurysm after robot
      assisted laparoscopic partial nephrectomy.
AB  - OBJECTIVES: To determine the influence of the early unclamping technique on the
      risk of renal artery pseudoaneurysm during robot-assisted laparoscopic partial
      nephrectomy. METHODS: From January 2013 to October 2014, 96 patients underwent
      robot-assisted laparoscopic partial nephrectomy for renal masses at Tokyo Women's
      Medical University Hospital, Tokyo, Japan. Computed tomography angiography was
      carried out 3-4 days after surgery. Early in the series, renal hilum was left
      unclamped and renorrhaphy was subsequently carried out (conventional unclamping
      technique). An early unclamping technique has been used since November 2013.
      RESULTS: A total of 61 patients underwent robot-assisted laparoscopic partial
      nephrectomy with early unclamping, and 35 patients underwent robot-assisted
      laparoscopic partial nephrectomy with conventional unclamping. Ischemia time was
      significantly shorter in the early unclamping group (16.5 vs. 23.1 min; P <
      0.01). The early unclamping group showed a significantly lower incidence of
      asymptomatic renal artery pseudoaneurysm relative to the conventional unclamping
      group (11.4% vs. 28.6%; P = 0.03). Multivariate analysis showed that the early
      unclamping technique was a significant independent factor in reducing the risk of
      renal artery pseudoaneurysm (hazard ratio 0.27; P = 0.01). CONCLUSIONS: The
      present findings suggest that an early unclamping technique might reduce ischemic
      time and risk of renal artery pseudoaneurysm. The absence of arterial bleeding
      before renorrhaphy is likely to be a key step in preventing renal artery
      pseudoaneurysm during robot-assisted laparoscopic partial nephrectomy.

PMID- 26307334
TI  - Pentacoordinated carboxylate pi-allyl nickel complexes as key intermediates for
      the Ni-catalyzed direct amination of allylic alcohols.
AB  - Direct amination of allylic alcohols with primary and secondary amines catalyzed
      by a system made of [Ni(1,5-cyclooctadiene)2 ] and 1,1'
      bis(diphenylphosphino)ferrocene was effectively enhanced by adding nBu4 NOAc and
      molecular sieves, affording the corresponding allyl amines in high yield with
      high monoallylation selectivity for primary amines and high regioselectivity for
      monosubstituted allylic alcohols. Such remarkable additive effects of nBu4 NOAc
      were elucidated by isolating and characterizing some nickel complexes,
      manifesting the key role of a charge neutral pentacoordinated eta(3) -allyl
      acetate complex in the present system, in contrast to usual cationic
      tetracoordinated complexes earlier reported in allylic substitution reactions. 

PMID- 26307336
TI  - Optimal sequential Bayesian analysis for degradation tests.
AB  - Degradation tests are especially difficult to conduct for items with high
      reliability. Test costs, caused mainly by prolonged item duration and item
      destruction costs, establish the necessity of sequential degradation test
      designs. We propose a methodology that sequentially selects the optimal
      observation times to measure the degradation, using a convenient rule that
      maximizes the inference precision and minimizes test costs. In particular our
      objective is to estimate a quantile of the time to failure distribution, where
      the degradation process is modelled as a linear model using Bayesian inference.
      The proposed sequential analysis is based on an index that measures the expected
      discrepancy between the estimated quantile and its corresponding prediction,
      using Monte Carlo methods. The procedure was successfully implemented for
      simulated and real data.

PMID- 26307337
TI  - A Preliminary Comparison of Laryngeal Manipulation and Postural Treatment on
      Voice Quality in a Prospective Randomized Crossover Study.
AB  - BACKGROUND: This crossover study compared the effects of two osteopathic
      treatments specific laryngeal manipulation (SLM) and postural manual therapy
      (PMT) on voice quality and pitch. METHODS: Twelve asymptomatic singers were
      measured acoustically immediately before and immediately after each intervention
      using a laryngograph. Fundamental frequency and the glottal closing quotient were
      used to determine any differences between groups before and after. RESULTS:
      Fundamental frequency showed a statistically significant change following both
      interventions (combined [P = 0.007] and PMT and SLM individually (P = 0.0143, P =
      0.018, respectively). Although the benefit demonstrated using SLM was greater
      than that with PMT (2.4, 2.02, respectively), following Bonferroni correction
      there was no statistical significance demonstrated between the two groups. There
      was no statistically significant change with glottal closing time for any
      intervention or at any time (P = 0.52). CONCLUSION: This pilot study provides
      evidence of the benefit for both SLM and PMT in singers. A significant difference
      was found in the voice quality of the participants involved in both PMT and SLM.
      These results set the way for further larger scale studies to evaluate group
      interactions and potential benefits in symptomatic patients.

PMID- 26307335
TI  - Considerations of Protein Subpockets in Fragment-Based Drug Design.
AB  - While the fragment-based drug design approach continues to gain importance, gaps
      in the tools and methods available in the identification and accurate utilization
      of protein subpockets have limited the scope. The importance of these features of
      small molecule-protein recognition is highlighted with several examples. A
      generalized solution for the identification of subpockets and corresponding
      chemical fragments remains elusive, but there are numerous advancements in
      methods that can be used in combination to address subpockets. Finally,
      additional examples of approaches that consider the relative importance of small
      molecule co-dependence of protein conformations are highlighted to emphasize an
      increased significance of subpockets, especially at protein interfaces.

PMID- 26307338
TI  - Development and Validation of the Children's Voice Handicap Index-10 for Parents.
AB  - OBJECTIVES/HYPOTHESIS: The Children's Voice Handicap Index-10 (CVHI-10) was
      introduced as a tool for self-assessment of children's dysphonia. However, in the
      management of children with voice disorders, both parents' and children's
      perspectives play an important role. Because a self-tool including both a
      children's and a parents' version does not exist yet, the aim of the study was to
      develop and validate an assessment tool which parallels the CVHI-10 for parents
      to assess the level of voice handicap in their child's voice. STUDY DESIGN:
      Observational, prospective, cross-sectional study. METHODS: To develop a CVHI-10
      for parents, called "CVHI-10-P", the CVHI-10 items were adapted to reflect
      parents' responses about their child. Fifty-five children aged 7-12 years
      completed the CVHI-10, whereas their parents completed the CVHI-10-P. Each
      child's voice was also perceptually assessed by an otolaryngologist using the
      Grade Breathness Roughness (GRB) scale. Fifty-one of the 55 children underwent
      voice therapy (VT) and were assessed afterward using the GRB, CVHI-10, and CVHI
      10-P. RESULTS: CVHI-10-P internal consistency was satisfactory (Cronbach alpha =
      .78). Correlation between CVHI-10-P and CVHI-10 was moderate (r = 0.37). CVHI-10
      P total scores were lower than CVHI-10 scores in most of the cases. Single-item
      mean scores were always lower in CVHI-10-P compared with CVHI-10, with the
      exception of the only one item of the CVHI-10-P that directly involves the
      parent's experience (item 10). Data gained from one tool are not directly related
      to the other, suggesting that these two tools appraise the child's voice handicap
      from different perspectives. The overall perceptual assessment scores of the 51
      children after VT significantly improved. There was a statistically significant
      reduction of the total scores and for each item in CVHI-10 and CVHI-10-P after
      VT. These data support the adoption of the CVHI-10-P as an assessment tool and an
      outcome measure for management of children's voice disorders. CONCLUSIONS: CVHI
      10-P is a valid tool to appraise parents' perspective of their child's voice
      disorder. The use of the CVHI-10 and the CVHI-10-P is recommended for objectively
      determining the level of voice handicap in children by parents and child.

PMID- 26307339
TI  - Antibody deficiency in Rubinstein-Taybi syndrome.
AB  - The developmental disorder Rubinstein-Taybi syndrome (RTS) is frequently
      complicated by recurrent respiratory infections. In many cases this is likely to
      be the result of microaspiration or gastro-oesophageal reflux but, in a
      proportion, underlying antibody deficiency is a potentially modifiable
      susceptibility factor for infection. Relatively subtle, specific defects of
      pneumococcal antibody production have previously been described in the context of
      RTS. Here, we report a rare association between the syndrome and an overt, major
      primary antibody deficiency disorder (common variable immune deficiency) which
      was successfully managed with immunoglobulin replacement therapy. Early
      recognition and investigation for antibody deficiency associated with RTS allied
      to effective and optimized treatment are essential to minimize morbidity and
      mortality and improve quality and duration of life. 

PMID- 26307341
TI  - Corrigendum.

PMID- 26307343
TI  - Reply to Dr. Regina and colleagues re: protein-derived acetaminophen-cysteine in
      supratherapeutic ingestion.

PMID- 26307342
TI  - Chemopreventive effects of Strobilanthes crispus leaf extract on azoxymethane
      induced aberrant crypt foci in rat colon.
AB  - In this work, microscopic and histological studies suggest that Strobilanthes
      crispus ethanol extract reduce azoxymethane (AOM)-induced colonic aberrant crypt
      foci (ACF) in rats. S. crispus is considered a traditional medicine and used as
      an antioxidant. Its leaf contains a large amount of phenolic compounds to which
      its radical scavenging role is attributed and enhance its ability to eradicate
      oxidative stress reactions. The study was designed to determine the
      chemopreventive effect of S. crispus ethanol extract in vivo and in vitro by
      elucidating the effect of the extract on intermediate biomarkers which can be
      used as effective predictors of colon cancer. S. crispus was analyzed for DPPH
      free radical scavenging, nitric oxide (NO) and ferric acid reduction. The results
      indicated that S. crispus oral administration significantly inhibited colorectal
      carcinogenesis induced by AOM as revealed by the reduction in the number of ACF.
      S. crispus down-regulated the expression of PCNA, Bcl2 and beta-catenin.
      Additionally, it exerted a pronounced inhibitory effect on MDA and NO levels and
      stimulatory effect on CAT and GPx activities. These results demonstrate that S.
      crispus is a chemopreventive agent for colorectal cancer through the suppression
      of early and intermediate carcinogenic phases that may be related to its
      flavonoid content. 

PMID- 26307344
TI  - Determination of Eligibility in Related Pediatric Hematopoietic Cell Donors:
      Ethical and Clinical Considerations. Recommendations from a Working Group of the
      Worldwide Network for Blood and Marrow Transplantation Association.
AB  - Related donors for hematopoietic cell (HC) transplantation are a growing
      population in recent years because of expanding indications for allogeneic
      transplantation. The safety and welfare of the donor are major concerns for the
      transplantation community, especially for related sibling donors of young
      recipients who are children and, thus, not able to fully consent. Because
      donation of HC does not improve the donor's own physical health and carries a
      risk of side effects, careful assessment of medical risks specific to the
      individual donor, as well as consideration of ethical and legal aspects
      associated with donation from a child, must be considered. In addition, donor
      centers must balance the needs of both the donor and the recipient, understanding
      the inherent conflict parents may have as they can be overly focused on the very
      sick child receiving a transplant, rather than on the relatively less significant
      health or emotional problems that a sibling donor may have, which could impact
      risk with donation. Likewise, consideration must be made regarding the nature of
      the relationship of the sibling donor to the recipient and also aspects of
      performing research on pediatric HC donors. In this article, as members of the
      Donor Issues Committee of the Worldwide Network for Blood and Marrow
      Transplantation, we review key ethical concerns associated with pediatric
      donation and then give recommendations for screening potential child donors with
      underlying health conditions. These recommendations are aimed at protecting the
      physical and emotional well-being of childhood donors and arise out of the Third
      International Conference on Health and Safety of Donors sponsored by the
      Worldwide Network for Blood and Marrow Transplantation. 

PMID- 26307345
TI  - Overall Survival Is Impacted by Birthplace and Not Extent of Surgery in Asian
      Americans with Resectable Gastric Cancer.
AB  - Survival from gastric cancer in the USA still lags behind Asia. Genetic,
      environmental, and tumor biology differences, along with extent of surgery have
      been implicated. Our aim was to evaluate survival outcomes in Asian-American
      gastric cancer patients undergoing surgical resection by comparing place of birth
      and clinicopathologic characteristics (including evaluation of 15 lymph
      nodes).The Surveillance, Epidemiology, and End Results database was queried to
      identify patients treated surgically for gastric cancer with curative intent in
      the USA (2000-2010). US-born versus foreign-born Asian-American patients were
      analyzed for survival. Secondary comparison was made to non-Asian patients. Stage
      IV and non-surgical patients were excluded. Of 10,089 patients identified, 1467
      patients were Asian: 271 were born in the USA, and 1196 were born outside the
      USA. Median survival was 32 months for non-Asians and 29 months for US-born
      Asians versus 61 months for Asian immigrants (p < 0.001). On multivariable
      analysis of overall survival in Asian patients, only US birthplace, older age,
      and higher stage yielded a significantly poorer outcome. Asian-American patients
      have a worse prognosis if born in the USA. Anatomic and surgical differences do
      not explain this disparity; environmental factors may be responsible.

PMID- 26307346
TI  - Red Cell Transfusion Triggers and Postoperative Outcomes After Major Surgery.
AB  - BACKGROUND: The effect of packed red blood cell (PRBC) transfusion on
      postoperative outcomes of patients undergoing major surgery remains unclear. We
      sought to determine the impact of blood utilization, as well as transfusion
      practices, on perioperative outcomes of patients undergoing cardiothoracic
      vascular (CT-V) and gastrointestinal (GI) procedures. METHODS: Patients who
      underwent major surgical procedures at Johns Hopkins Hospital between 2009 and
      2014 were identified. Data on perioperative hemoglobin (Hb) and blood utilization
      were obtained; transfusion strategy was categorized as liberal (Hb trigger >=7
      g/dL) vs. restrictive (Hb trigger <7 g/dL). Risk-adjusted logistic regression
      models and propensity score matching were used to assess the association between
      transfusion triggers and perioperative morbidity. RESULTS: Among 10,163 patients
      undergoing either CT-V (50.9 %) or GI (49.1 %) surgery, 4401 (43.3 %) patients
      received PRBCs. Of the 4401 patients transfused, 71.2 % were transfused using a
      liberal trigger (>=7 g/dL hemoglobin), while 28.8 % had a restrictive trigger (<7
      g/dL). The median number of PRBCs transfused was 3 (restrictive 5 vs. liberal 2
      units). While ischemic adverse events were more common among patients undergoing
      CT-V surgery (17.3 %), infection was the more common complication among patients
      undergoing GI surgery (11.9 %). American Society of Anesthesiologist (ASA) class
      3-4, Charlson score >=3, and total units of transfused PRBCs were independently
      associated with overall complications (all P < 0.05). Patients in the restrictive
      transfusion group did not have increased risk of complications compared with the
      liberal transfusion group on multivariable analysis (odds ratio (OR) 1.16, 95 %
      confidence interval (CI) 0.98-1.38; P = 0.08) or after propensity score matching
      (OR 1.04, 95 % CI 0.88-1.22; P = 0.65). CONCLUSIONS: Liberal transfusion triggers
      after major surgery were more common than restrictive practice. Patients with
      restrictive transfusion trigger did not have increased risk for complications
      compared with patients transfused with a liberal trigger.

PMID- 26307347
TI  - Comorbidity between depression and inflammatory bowel disease explained by immune
      inflammatory, oxidative, and nitrosative stress; tryptophan catabolite; and gut
      brain pathways.
AB  - The nature of depression has recently been reconceptualized, being conceived as
      the clinical expression of activated immune-inflammatory, oxidative, and
      nitrosative stress (IO&NS) pathways, including tryptophan catabolite (TRYCAT),
      autoimmune, and gut-brain pathways. IO&NS pathways are similarly integral to the
      pathogenesis of inflammatory bowel disease (IBD). The increased depression
      prevalence in IBD associates with a lower quality of life and increased morbidity
      in IBD, highlighting the role of depression in modulating the pathophysiology of
      IBD.This review covers data within such a wider conceptualization that better
      explains the heightened co-occurrence of IBD and depression. Common IO&NS
      underpinning between both disorders is evidenced by increased pro-inflammatory
      cytokine levels, eg, interleukin-1 (IL-1) and tumor necrosis factor-alpha, IL-6
      trans-signalling; Th-1- and Th-17-like responses; neopterin and soluble IL-2
      receptor levels; positive acute phase reactants (haptoglobin and C-reactive
      protein); lowered levels of negative acute phase reactants (albumin, transferrin,
      zinc) and anti-inflammatory cytokines (IL-10 and transforming growth factor
      beta); increased O&NS with damage to lipids, proteinsm and DNA; increased
      production of nitric oxide (NO) and inducible NO synthase; lowered plasma
      tryptophan but increased TRYCAT levels; autoimmune responses; and increased
      bacterial translocation. As such, heightened IO&NS processes in depression
      overlap with the biological underpinnings of IBD, potentially explaining their
      increased co-occurrence. This supports the perspective that there is a spectrum
      of IO&NS disorders that includes depression, both as an emergent comorbidity and
      as a contributor to IO&NS processes. Such a frame of reference has treatment
      implications for IBD when "comorbid" with depression. 

PMID- 26307348
TI  - Quantification of lipoic acid from skin samples by HPLC using ultraviolet,
      electrochemical and evaporative light scattering detectors.
AB  - Lipoic acid (LA) is an endogenous organosulfur compound with potent antioxidant
      property. LA is often used as a drug for the treatment of skin disorders. For the
      accomplishment of topical applications of LA appropriate drug quantification
      methods are essential. Thus far, no HPLC methods have been reported for the
      measurement of LA extracted from skin. In this article we report on the
      development and validation of three sensitive and specific HPLC methods for LA
      and dihydrolipoic acid (DHLA) using ultraviolet (UV), electrochemical (EC) or
      evaporative light scattering (ELS) detection. These methods demonstrate different
      linearity ranges. The chromatographic separations were performed by RP-HPLC (250
      * 4 mm, 5 MUm) with isocratic elution using an acidic mobile phase for the three
      detection techniques. The lower limits of detection and quantification were 0.04
      and 0.08 ng LA, respectively, for HPLC coupled to ELS, an innovative detector for
      LA with high sensitivity. The extraction of LA from skin samples showed
      recoveries greater than 71%. The recovered LA concentrations from stratum corneum
      and epidermis+dermis layers were: 5.41 +/- 0.56 and 4.92 +/- 0.33 MUg/mL,
      respectively for HPLC/UV and 6.52 +/- 0.49 and 5.01 +/- 0.41 MUg/mL,
      respectively, for HPLC/EC for the added LA concentration (6.67 MUg/mL), and 8.88
      +/- 0.46 and 8.95 +/- 0.08 MUg/mL, respectively, for HPLC/ELS for the added LA
      concentration (10 MUg/mL). These three optimized HPLC methods allowed for a
      simple, rapid and reliable determination of LA in human skin. They should be
      useful for the development of drug delivery systems for topical applications of
      LA.

PMID- 26307349
TI  - Immunomodulatory properties of stem cells and bioactive molecules for tissue
      engineering.
AB  - The immune system plays a crucial role in the success of tissue engineering
      strategies. Failure to consider the interactions between implantable scaffolds,
      usually containing cells and/or bioactive molecules, and the immune system can
      result in rejection of the implant and devastating clinical consequences.
      However, recent research into mesenchymal stem cells, which are commonly used in
      many tissue engineering applications, indicates that they may play a beneficial
      role modulating the immune system. Likewise, direct delivery of bioactive
      molecules involved in the inflammatory process can promote the success of tissue
      engineering constructs. In this article, we will review the various mechanisms in
      which modulation of the immune system is achieved through delivered bioactive
      molecules and cells and contextualize this information for future strategies in
      tissue engineering. 

PMID- 26307350
TI  - Hybrid pulmonary surfactant-coated nanogels mediate efficient in vivo delivery of
      siRNA to murine alveolar macrophages.
AB  - The local delivery of small interfering RNA (siRNA) to the lungs may provide a
      therapeutic solution to a range of pulmonary disorders. Resident alveolar
      macrophages (rAM) in the bronchoalveolar lumen play a critical role in lung
      inflammatory responses and therefore constitute a particularly attractive target
      for siRNA therapeutics. However, achieving efficient gene silencing in the lung
      while avoiding pulmonary toxicity requires appropriate formulation of siRNA in
      functional nanocarriers. In this study, we evaluated pulmonary surfactant-coated
      dextran nanogels for the delivery of siRNA to rAM upon pharyngeal aspiration in
      BALB/c mice. Both the surfactant-coated and uncoated nanogels achieved high
      levels of siRNA uptake in rAM, yet only the surfactant-coated formulation could
      significantly reduce gene expression on the protein level. Surfactant-coated
      nanogels induced a profound downregulation of target mRNA levels, reaching 70%
      knockdown with ~1mgkg(-1) siRNA dose. In addition, only mild acute pro
      inflammatory cytokine and chemokine responses were detected one day after
      nanoparticle aspiration, accompanied by a moderate neutrophil infiltration in the
      bronchoalveolar lumen. The latter could be substantially reduced by removal of
      excess surfactant from the formulation. Overall, our hybrid core-shell
      nanoparticles have demonstrated safe and effective siRNA delivery to rAM,
      providing a new therapeutic approach for treatment of inflammatory pathologies in
      the lung. 

PMID- 26307351
TI  - Co-delivery of VEGF and Bcl-2 dual-targeted siRNA polymer using a single
      nanoparticle for synergistic anti-cancer effects in vivo.
AB  - Cancer is a multifactorial disease which involves complex genetic mutation and
      dysregulation. Combinatorial RNAi technology and concurrent multiple gene
      silencing are expected to provide advanced strategies for effective cancer
      therapy, but a safe and effective carrier system is a prerequisite to successful
      siRNA delivery in vivo. We previously developed an effective tumor-targeting
      siRNA delivery system for in vivo application. In response to the success of this
      development, herein we present a dual-gene targeted siRNA and its delivery
      system, to achieve synergistic effects in cancer therapy. Two different sequences
      of siRNA were chemically modified to be randomly copolymerized in a single
      backbone of siRNA polymer (Dual-poly-siRNA), and the resulting Dual-poly-siRNA
      was incorporated into tumor-homing glycol chitosan nanoparticles. Based on the
      stability in serum and delivery in a tumor-targeted manner, intravenously
      administered Dual-poly-siRNA carrying glycol chitosan nanoparticles (Dual-NP)
      demonstrated successful dual-gene silencing in tumors. Notably, co-delivery of
      VEGF and Bcl-2 targeting siRNA led to more effective cancer therapy for
      convenient application. 

PMID- 26307352
TI  - BoHV-4 immediate early 1 gene is a dispensable gene and its product is not a bone
      marrow stromal cell antigen 2 counteracting factor.
AB  - BACKGROUND: Bovine herpesvirus 4 (BoHV-4) is a gammaherpesvirus whose genome was
      cloned as Bacterial Artificial Chromosome (BAC) and exploited as a gene delivery
      vector for vaccine purposes. Although BoHV-4 genome has been completely sequenced
      and its open reading frames (ORFs) structurally defined in silico, most of them
      are not functionally characterized. In BoHV-4 genome two major immediate early
      genes (IE) are present, IE1 and IE2. IE2 is an essential gene because its removal
      from the viral genome renders the virus unable to replicate, whereas for IE1 no
      many functional information are available. RESULTS: In this work, IE1
      contribution in initiating and maintaining BoHV-4 lytic replication was assessed
      generating a recombinant BoHV-4 genome lacking of IE1 gene, BoHV-4DeltaIE1. In
      contrast to BoHV-4IE2 deleted mutant, BoHV-4DeltaIE1 infectious replicating viral
      particles (IRVPs) could be reconstituted following viral DNA electroporation in
      permissive cells. However the titer of BoHV-4DeltaIE1 IRVPs produced into the
      cell supernatant and BoHV-4DeltaIE1 plaques size were reduced respect to BoHV-4
      undeleted control. Further the impaired BoHV-4DeltaIE1 IRVPs produced into the
      cell supernatant could be rescued by expressing IE1 gene product in trans,
      confirming the implication of IE1 in BoHV-4 lytic replication. Next, the possible
      role of BoHV-4IE1 as bone marrow stromal cell antigen 2 (BST-2) counteracting
      factor, as hypothesized by IE1 amino-terminal gene product homology with Kaposi
      Sarcoma Associated Herpesvirus (KSHV) K5, was excluded too. CONCLUSIONS: Although
      the real function of BoHV-4IE1 is still elusive, a new BoHV-4 genome gene locus
      as a target site for the insertion of foreign DNA and resulting in the
      attenuation of the virus has been revealed. These data can be considered of
      relevance to improve BoHV-4 gene delivery properties.

PMID- 26307353
TI  - GelJ--a tool for analyzing DNA fingerprint gel images.
AB  - BACKGROUND: DNA fingerprinting is a technique for comparing DNA patterns that has
      applications in a wide variety of contexts. Several commercial and freely
      available tools can be used to analyze DNA fingerprint gel images; however,
      commercial tools are expensive and usually difficult to use; and, free tools
      support the basic functionality for DNA fingerprint analysis, but lack some
      instrumental features to obtain accurate results. RESULTS: In this paper, we
      present GelJ, a feather-weight, user-friendly, platform-independent, open-source
      and free tool for analyzing DNA fingerprint gel images. Some of the outstanding
      features of GelJ are mechanisms for accurate lane- and band-detection, several
      options for computing migration models, a number of band- and curve-based
      similarity methods, different techniques for generating dendrograms, comparison
      of banding patterns from different experiments, and database support.
      CONCLUSIONS: GelJ is an easy to use tool for analyzing DNA fingerprint gel
      images. It combines the best characteristics of both free and commercial tools:
      GelJ is light and simple to use (as free programs), but it also includes the
      necessary features to obtain precise results (as commercial programs). In
      addition, GelJ incorporates new functionality that is not supported by any other
      tool.

PMID- 26307355
TI  - Acid loaded porphyrin-based metal-organic framework for ammonia uptake.
AB  - A porphyrin-based metal-organic framework is shown to be structurally stable
      towards acid loading using either hydrochloric or formic acid. The capacity of
      this material as an ammonia sorbent was analysed using micro-breakthrough
      experiments in both dry and humid ammonia flows. The acid loaded material
      exhibited excellent uptake in comparison with the parent MOF. 

PMID- 26307354
TI  - Rheumatoid factor, not antibodies against citrullinated proteins, is associated
      with baseline disease activity in rheumatoid arthritis clinical trials.
AB  - INTRODUCTION: Although the prognostic value of rheumatoid factor (RF) and
      autoantibodies against citrullinated proteins (ACPAs) in patients with rheumatoid
      arthritis (RA) is well established, their association with RA disease activity
      remains unclear. Here, we investigate this association in a large study using
      data from clinical trials. METHODS: We used baseline data from four recent
      randomized controlled clinical trials of RA. We investigated individual and
      composite measures of disease activity. The relationship of RF and ACPAs with
      these measures was investigated by using stratified analysis (comparing four
      groups of patients according to the presence or absence of RF and ACPAs) and
      matched analysis (disease activity levels compared between patients negative and
      patients highly positive for one autoantibody who were matched for levels of the
      other autoantibody as well as for age, gender, and duration of RA). RESULTS: A
      total of 2118 patients were analysed in the different cohorts. In the stratified
      analysis, RF(+) patients, regardless of ACPA status, had the highest levels of
      disease activity, whereas ACPA(+) patients had disease activity that was similar
      to or lower than that of ACPA(-) patients, both in the presence and in the
      absence of RF. When matched for ACPA levels, patients with highly positive RF had
      significantly higher disease activity for all composite indices compared with
      patients who were RF(-) (P = 0.0067), whereas ACPA-highly-positive and ACPA
      negative patients matched for RF levels had similar disease activity, again even
      with the tendency toward lower disease activity for ACPA(+) patients (P = 0.054).
      CONCLUSION: The data presented suggest that the presence of RF has a clear
      association with higher levels of disease activity but that the presence of ACPAs
      has not and even appears to be associated with lower disease activity.

PMID- 26307357
TI  - Fifty seven years of follow-up of the Israeli cohort of Laron Syndrome patients
      From discovery to treatment.
AB  - Clinical and laboratory investigations of dwarfed children newly Jewish
      immigrants from Yemen and Middle East and who resembled patients with isolated
      growth hormone deficiency were started by our group in 1958. In 1963 when we
      found that they have high serum levels of hGH, we knew that we had discovered a
      new disease of primary GH insensitivity. It was subsequently coined Laron
      Syndrome (LS, OMIM #262500). The etiopathogenesis was disclosed by 2 liver
      biopsies demonstrating a defect in the GH receptor. Subsequent investigations
      demonstrated deletions or mutations in the GHR gene. The defect lead to an
      inability of IGF-I generation, resulting in severe dwarfism, obesity, and other
      morphologic and biochemical pathologies due to IGF-I deficiency. With the
      biosynthesis of IGF-I in 1986, therapeutic trials started. Following closely our
      cohort of 69 patients with LS enabled us to study its features in untreated and
      IGF-I treated patients. This syndrome proved to be a unique model to investigate
      the effects of IGF-I dissociated from GH stimulation. In recent studies we found
      that homozygous patients for the GHR mutations are protected lifelong from
      developing malignancies, opening new directions of research.

PMID- 26307356
TI  - Brain structural deficits and working memory fMRI dysfunction in young adults who
      were diagnosed with ADHD in adolescence.
AB  - When adolescents with ADHD enter adulthood, some no longer meet disorder
      diagnostic criteria but it is unknown if biological and cognitive abnorma lities
      persist. We tested the hypothesis that people diagnosed with ADHD during
      adolescence present residual brain abnormalities both in brain structure and in
      working memory brain function. 83 young adults (aged 20-24 years) from the
      Northern Finland 1986 Birth Cohort were classified as diagnosed with ADHD in
      adolescence (adolescence ADHD, n = 49) or a control group (n = 34). Only one
      patient had received medication for ADHD. T1-weighted brain scans were acquired
      and processed in a voxel-based analysis using permutation-based statistics. A sub
      sample of both groups (ADHD, n = 21; controls n = 23) also performed a Sternberg
      working memory task whilst acquiring fMRI data. Areas of structural difference
      were used as a region of interest to evaluate the implications that structural
      abnormalities found in the ADHD group might have on working memory function.
      There was lower grey matter volume bilaterally in adolescence ADHD participants
      in the caudate (p < 0.05 FWE corrected across the whole brain) at age 20-24.
      Working memory was poorer in adolescence ADHD participants, with associated
      failure to show normal load-dependent caudate activation. Young adults diagnosed
      with ADHD in adolescence have structural and functional deficits in the caudate
      associated with abnormal working memory function. These findings are not
      secondary to stimulant treatment, and emphasise the importance of taking a wider
      perspective on ADHD outcomes than simply whether or not a particular patient
      meets diagnostic criteria at any given point in time. 

PMID- 26307358
TI  - Solitary Langerhans cell histiocytosis of the occipital condyle: a case report
      and review of the literature.
AB  - BACKGROUND: Despite the recent advent of various radiographic imaging techniques,
      it is still very difficult to correctly distinguish a pediatric osteolytic lesion
      in the occipital condyle, which makes it further complicated to decide on the
      necessity of and the adequate timing for radical resection and craniocervical
      fusions. To establish a legitimate therapeutic strategy for this deep-seated
      lesion, surgical biopsy is a reasonable choice for first-line intervention. The
      choice of surgical approach becomes very important because a sufficient amount of
      histological specimen must be obtained to confirm the diagnosis but, ideally, the
      residual bony structures and the muscular structures should be preserved so as
      not to increase craniocervical instability. In this report, we present our
      experience with a case of solitary Langerhans cell histiocytosis (LCH) involving
      the occipital condyle that was successfully treated with minimally invasive
      surgical biopsy with a far lateral condylar approach supported by preoperative 3D
      computer graphic simulation. CASE REPORT: An 8-year-old girl presented with neck
      pain. Magnetic resonance imaging and computed tomography (CT) revealed an
      osteolytic lesion of the left occipital condyle. At surgery, the patient was
      placed in the prone position. A 3-cm skin incision was made in the posterior
      auricular region, and the sternocleidomastoid and splenius capitis muscles were
      dissected in the middle of the muscle bundle along the direction of the muscle
      fiber. Under a navigation system, we approached the occipital condyle through the
      space between the longissimus capitis muscle and the posterior belly of the
      digastric muscle and lateral to the superior oblique muscle, verifying each
      muscle at each depth of the surgical field and, finally, obtained sufficient
      surgical specimen. After the biopsy, her craniocervical instability had not
      worsened, and chemotherapy was performed. Twelve weeks after chemotherapy, her
      neck pain had gradually disappeared along with her torticollis, and CT showed
      remission of the lesion and marked regeneration of the left occipital condyle.
      Within our knowledge, this is the first reported case of LCH involving the
      occipital condyle. Although very rare, our case indicated that LCH can be an
      alternative in the differential diagnosis of osteolytic lesions in the
      craniocervical junction, in which early bone regeneration with sufficient
      cervical stability is expected after chemotherapy. CONCLUSIONS: In cases of
      pediatric osteolytic lesions, when they initially presented with apparent
      cervical instability, craniocervical fusion may possibly become unnecessary after
      a series of treatments. Thus, the effort to maximally preserve the
      musculoskeletal structure should be made until its histological diagnosis is
      finally confirmed.

PMID- 26307359
TI  - Traditional preference of Wild Edible Fruits (WEFs) for digestive disorders (DDs)
      among the indigenous communities of Swat Valley-Pakistan.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Digestive disorders (DDs) causes indisposition
      and lead to death, especially in the underdeveloped world where hygienic
      conditions are scarce. A major proportion of the human populace depends on the
      use of traditional knowledge about the consumption of medicinal plants for many
      diseases, including DDs. The contemporary study summarizes the indigenous uses of
      Wild Edible Fruits (WEFs) of Swat Valley used for DDs and to evaluate the bio
      efficacy of these pharmacologically essential fruit species from the available
      literature. MATERIAL AND METHODS: An ethnomedicinal study was conducted in Swat
      valley, Northern Pakistan. Data was collected through field assessment as well as
      from traditional healers and local people by means of personal interviews and
      semi-structured questionnaires, giving value to both rural and urban communities.
      The ethnomedicinal knowledge was quantitatively analysed using various indices
      like Familiarity Index (FI), Consensus index (CI), Informant consensus factor
      (ICF) and the present data was compared with previous studies in the neighbouring
      areas using Jaccard similarity coefficient (JI). RESULTS: The present study
      recorded use reports on 53 WEFs of ethnomedicinal prominence in the treatment of
      DDs, belonging to 23 families. The recurrent growth forms were trees (51%) shrubs
      (38%) and herbs (11%). High consumption of fruits (50%), leaves (27%) and flowers
      (12%) was recorded. The traditional preparations were mostly in the form of
      unprocessed dried/fresh, powder, Juice and decoction and were usually taken
      orally. Almost 20-30% of the plants occurred in synanthropic vegetation while
      more than 75% were found in natural woodland and grassland vegetation. Family
      Berberidaceae dominated with highest FIV (41) followed by Punicaceae (38),
      Oxalidaceae (36) and Moraceae (35). ICF values for carminative (0.6) showed high
      consensus factor followed by anthelmintic, gastroenteritis and intestinal
      disorders (0.5). FI value is high for Berberis lycium (0.5), Morus alba (0.5),
      Morus nigra (0.5) followed by Olea ferruginea (0.45). B. lycium had the high
      consensus index, whereas, a study conducted on Lesser Himalayas Pakistan showed
      high value of Jaccard similarity coefficient. CONCLUSION: WEFs are predominantly
      used in the treatment of various diseases in the valley and traditional knowledge
      about the use of these species against DDs is still prevailing. Multiple uses of
      these WEFs suggest further investigation into its phytochemical, toxicological
      and pharmaceutical potential. This study will serve as a baseline data for future
      pharmacological studies.

PMID- 26307360
TI  - Hybrid surgery versus anterior cervical discectomy and fusion for multilevel
      cervical degenerative disc diseases: a meta-analysis.
AB  - The objective of this meta-analysis is to compare hybrid surgery (HS) and
      cervical discectomy and fusion (ACDF) for multilevel cervical degenerative disc
      diseases (DDD). Systematic searches of all published studies through March 2015
      were identified from Cochrane Library, Medline, PubMed, Embase, ScienceDirect,
      CNKI, WANFANG DATA and CQVIP. Randomized controlled trials (RCTs) and non-RCTs
      involving HS and ACDF for multilevel DDD were included. All literature was
      searched and assessed by two independent reviewers according to the standard of
      Cochrane systematic review. Data of functional and radiological outcomes in two
      groups were pooled, which was then analyzed by RevMan 5.2 software. One RCT and
      four non-RCTs encompassing 160 patients met the inclusion criteria. Meta-analysis
      revealed significant differences in blood loss (p = 0.005), postoperative C2-C7
      ROM (p = 0.002), ROM of superior adjacent segment (p < 0.00001) and ROM of
      inferior adjacent segment (p = 0.0007) between the HS group and the ACDF group.
      No significant differences were found regarding operation time (p = 0.75),
      postoperative VAS (p = 0.18) and complications (p = 0.73) between the groups.
      Hybrid surgery demonstrated excellent clinical efficacy and radiological results.
      Postoperative C2-C7 ROM was closer to the physiological status. No decrease in
      the ROM of the adjacent segment was noted in the hybrid surgery group. 

PMID- 26307361
TI  - A Trust-Based Pact in Research Biobanks. From Theory to Practice.
AB  - Traditional Informed Consent is becoming increasingly inadequate, especially in
      the context of research biobanks. How much information is needed by patients for
      their consent to be truly informed? How does the quality of the information they
      receive match up to the quality of the information they ought to receive? How can
      information be conveyed fairly about future, non-predictable lines of research?
      To circumvent these difficulties, some scholars have proposed that current
      consent guidelines should be reassessed, with trust being used as a guiding
      principle instead of information. Here, we analyse one of these proposals, based
      on a Participation Pact, which is already being offered to patients at the
      Istituto Europeo di Oncologia, a comprehensive cancer hospital in Milan, Italy. 

PMID- 26307362
TI  - Exploring the Impact of a Culturally Tailored Short Film in Modifying Dementia
      Stigma Among Chinese Americans: A Pilot Study.
AB  - OBJECTIVE: Chinese Americans, one of the fastest growing ethnic groups among the
      US elderly population, perceive high levels of dementia stigma. The authors
      examined the extent of the stigma and explored the impact of media through a
      culturally tailored short film to modify dementia stigma. METHODS: Chinese
      American participants were asked to answer a dementia questionnaire. A short film
      was then used to address the impact of media on dementia stigma. RESULTS: Among
      90 randomly selected participants, 89% (n = 80) found the short film to be a
      useful way to modify their misconceptions about dementia. In the comparison
      between the group who felt less influenced by the short film and the group who
      recognized the short film to be extremely helpful, the latter group had a higher
      baseline of stigma toward dementia, as well as a shorter duration of residence in
      the USA. CONCLUSION: Chinese Americans still perceive severe dementia stigma.
      Nevertheless, a culturally tailored short film demonstrated promising impact in
      modifying stigma toward dementia.

PMID- 26307363
TI  - Preparing and Training the College Mental Health Workforce.

PMID- 26307364
TI  - Demographic and Personal Characteristics of Male and Female Chairs in Academic
      Psychiatry.
AB  - OBJECTIVE: Despite the strong representation of female psychiatrists in residency
      and early-career positions, the number of female faculty sharply decreases in
      tenured or executive leadership positions. Why there exists a marked change in
      representation at the level of senior leadership within academic psychiatry is
      unclear. The authors investigated the causative factors contributing to this
      observation and gathered information about the personal characteristics of women
      in executive leadership roles. METHODS: The authors surveyed psychiatry chairs at
      academic institutions. They identified all female chairs and randomly selected a
      group of male chairs to serve as a control group. The survey assessed perceived
      barriers, strengths, and weaknesses and differences in demographics and
      leadership styles between female and male chairs. RESULTS: Ten percent of
      psychiatry chairs were female. Male chairs were more likely than female chairs to
      head large departments (p = 0.02, confidence interval (CI) -17.1-69.1) and had a
      higher H-index (p = 0.001, CI 6.6-37.2). Female chairs were more likely than male
      chairs to perceive barriers in their career development (p = 0.01, CI 0.7-2.2),
      citing little or no mentorship (p = 0.04), gender discrimination (p = 0.0001),
      and family obligations (p = 0.001) more often. CONCLUSION: Academic institutions
      must incorporate programs to decrease barriers and work to achieve equitable
      representation of women in upper-level leadership positions. Moreover, academic
      medicine must evolve to cultivate a family-friendly environment that successfully
      supports both genders.

PMID- 26307365
TI  - Influence of H2TOEtPyP4 porphyrin on the stability and conductivity of bilayer
      lipid membranes.
AB  - Many water-soluble cationic porphyrins are known to be prospective
      chemotherapeutics and photosensitizers for cancer treatment and diagnosis. The
      physicochemical properties of porphyrins, in particular their interactions with
      membranes, are important determining factors of their biological activity. The
      influence of cationic meso-tetra-[4-N-(2'-hydroxyethyl) pyridyl] porphyrin
      (H2TOEtPyP) on the stability and conductivity of bilayer lipid membranes (BLMs)
      was studied. H2TOEtPyP4 porphyrin was shown to decrease the stability of BLMs
      made of a mixture of DOPS and DPPE (1:1) in an electric field because of a
      reduction of line tension of spontaneously formed pore edges in the BLM. The
      presence of cationic porphyrin was found to reduce BLM surface tension. This
      effect was enhanced with increasing porphyrin concentration. H2TOEtPyP4 increased
      the probability of spontaneous pore formation. Further investigating the cyclic
      current-voltage characteristics of BLMs allowed determining the electrical
      capacity and conductivity of BLMs in the presence of H2TOEtPyP4 porphyrin. It was
      shown that in the presence of cationic porphyrin the electrical capacity as well
      as conductivity of the BLM increases. 

PMID- 26307366
TI  - Erratum: Mirror neuron therapy for hemispatial neglect patients.

PMID- 26307367
TI  - Children's clinical cancer trials: what needs to change to allow children access
      to new cancer drugs?
AB  - Despite numerous advances with the incorporation of multimodal treatment,
      children with cancers have a major unmet need to access new drugs. Still, a
      reduced number of new targeted drugs is evaluated in pediatric patients and very
      few of them progress into late phase trials and clinical use. Changes required
      include: increased collaboration between all stakeholders, improved understanding
      of disease biology and its incorporation into early clinical trials, faster and
      more efficient early and late clinical trials, better incentives for
      pharmaceutical companies and improving access to new drugs across the globe. 

PMID- 26307368
TI  - Attenuation of autophagic-proteolysis in C2C12 cells by saccharopine.
AB  - Muscle wasting impairs physical function and leads people to a bedridden state.
      We previously demonstrated that lysine (Lys) suppresses autophagic-proteolysis
      through the Akt pathway. However, the effect of metabolites of Lys on proteolysis
      is unclear. In this study, we investigated the effect of saccharopine (Sac), a
      metabolite of Lys, on proteolysis in C2C12 cells. When C2C12 myotubes were
      incubated in serum-free medium containing Sac, the rate of proteolysis, which was
      evaluated by 3-methylhistidine released from C2C12 myotubes, and autophagy
      activity, which was assessed by amount of light chain 3-II, were suppressed. Sac
      stimulated Akt and mammalian target of rapamycin signaling, which was evaluated
      from eIF4E-binding protein 1 phosphorylation. The suppressive effects of Sac on
      proteolysis and autophagy were completely abolished by an Akt inhibitor.
      Therefore, we concluded that Sac suppresses autophagic-proteolysis through Akt as
      with Lys.

PMID- 26307370
TI  - Stabilization of Titanium Dioxide Nanoparticles at the Surface of Carbon
      Nanomaterials Promoted by Microwave Heating.
AB  - TiO2 is frequently combined with carbon materials, such as reduced graphene oxide
      (RGO), to produce composites with improved properties, for example for
      photocatalytic applications. It is shown that heating conditions significantly
      affect the interface and photocatalytic properties of TiO2 @C, and that microwave
      irradiation can be advantageous for the synthesis of carbon-based materials.
      Composites of TiO2 with RGO or amorphous carbon were prepared from reaction of
      titanium isopropoxide with benzyl alcohol. During the synthesis of the TiO2
      nanoparticles, the carbon is involved in reactions that lead to the covalent
      attachment of the oxide, the extent of which depends on the carbon
      characteristics, heating rate, and mechanism. TiO2 is more efficiently stabilized
      at the surface of RGO than amorphous carbon. Rapid heating of the reaction
      mixture results in a stronger coupling between the nanoparticles and carbon, more
      uniform coatings, and smaller particles with narrower size distributions. The
      more efficient attachment of the oxide leads to better photocatalytic
      performance. 

PMID- 26307369
TI  - Epigenetic regulation of human adipose-derived stem cells differentiation.
AB  - Adult stem cells have more restricted differentiation potential than embryonic
      stem cells (ESCs), but upon appropriate stimulation can differentiate into cells
      of different germ layers. Epigenetic factors, including DNA modifications, take a
      significant part in regulation of pluripotency and differentiation of ESCs. Less
      is known about the epigenetic regulation of these processes in adult stem cells.
      Gene expression profile and location of DNA modifications in adipose-derived stem
      cells (ADSCs) and their osteogenically differentiated lineages were analyzed
      using Agilent microarrays. Methylation-specific PCR and restriction-based
      quantitative PCR were applied for 5-methylcytosine (5mC) and 5
      hydroxymethylcytosine (5hmC) detection in selected loci. The level of DNA
      modifications in the POU5F1 locus was quantified with deep sequencing. Expression
      levels of selected genes were assayed by real-time PCR. ADSCs differentiation
      into osteogenic lineages involved marked changes in both 5mC and 5hmC profiles,
      but 5hmC changes were more abundant. 5mC losses and 5hmC gains were the main
      events observed during ADSCs differentiation, and were accompanied by increased
      expression of TET1 (P = 0.009). In ADSCs, POU5F1 was better expressed than NANOG
      or SOX2 (P <= 0.001). Both 5mC and 5hmC marks were present in the POU5F1 locus,
      but only hydroxymethylation of specific cytosine showed significant effect on the
      gene expression. In summary, the data of our study suggest significant
      involvement of changes in 5hmC profile during the differentiation of human adult
      stem cells.

PMID- 26307371
TI  - Validation of a performance assessment instrument in problem-based learning
      tutorials using two cohorts of medical students.
AB  - Although problem-based learning (PBL) has been widely used in medical schools,
      few studies have attended to the assessment of PBL processes using validated
      instruments. This study examined reliability and validity for an instrument
      assessing PBL performance in four domains: Problem Solving, Use of Information,
      Group Process, and Professionalism. Two cohorts of medical students (N = 310)
      participated in the study, with 2 years of PBL evaluation data extracted from
      archive rated by a total of 158 faculty raters. Analyses based on
      generalizability theory were conducted for reliability examination. Validity was
      examined through following the Standards for Educational and Psychological
      Testing to evaluate content validity, response processes, construct validity,
      predictive validity, and the relationship to the variable of training. For
      construct validity, correlations of PBL scores with six other outcome measures
      were examined, including Medical College Admission Test, United States Medical
      Licensing Examination (USMLE) Step 1, National Board of Medical Examiners (NBME)
      Comprehensive Basic Science Examination, NBME Comprehensive Clinical Science
      Examination, Clinical Performance Examination, and USMLE Step 2 Clinical
      Knowledge. Predictive validity was examined by using PBL scores to predict five
      medical school outcomes. The highest percentage of PBL total score variance was
      associated with students (60 %), indicating students in the study differed in
      their PBL performance. The generalizability and dependability coefficients were
      moderately high (Ep(2) = .68, phi = .60), showing the instrument is reliable for
      ranking students and identifying competent PBL performers. The patterns of
      correlations between PBL domain scores and the outcome measures partially support
      construct validity. PBL performance ratings as a whole significantly (p < .01)
      predicted all the major medical school achievements. The second year PBL scores
      were significantly higher than those of the first year, indicating a training
      effect. Psychometric findings provided support for reliability and many aspects
      of validity of PBL performance assessment using the instrument.

PMID- 26307372
TI  - Photosynthetic traits of Siebold's beech seedlings in changing light conditions
      by removal of shading trees under elevated CO2.
AB  - The purpose of this study was to obtain basic information on acclimation capacity
      of photosynthesis in Siebold's beech seedlings to increasing light intensity
      under future elevated CO2 conditions. We monitored leaf photosynthetic traits of
      these seedlings in changing light conditions (before removal of shade trees, the
      year after removal of shade trees and after acclimation to open conditions) in a
      10-year free air CO2 enrichment experiment in northern Japan. Elevated CO2 did
      not affect photosynthetic traits such as leaf mass per area, nitrogen content and
      biochemical photosynthetic capacity of chloroplasts (i.e. maximum rate of
      carboxylation and maximum rate of electron transport) before removal of the shade
      trees and after acclimation to open conditions; in fact, a higher net
      photosynthetic rate was maintained under elevated CO2 . However, in the year
      after removal of the shade trees, there was no increase in photosynthesis rate
      under elevated CO2 conditions. This was not due to photoinhibition. In ambient
      CO2 conditions, leaf mass per area and nitrogen content were higher in the year
      after removal of shade trees than before, whereas there was no increase under
      elevated CO2 conditions. These results indicate that elevated CO2 delays the
      acclimation of photosynthetic traits of Siebold's beech seedlings to increasing
      light intensity. 

PMID- 26307373
TI  - Quantitative Dobutamine Stress Echocardiography Using Speckle-Tracking Analysis
      versus Conventional Visual Analysis for Detection of Significant Coronary Artery
      Disease after ST-Segment Elevation Myocardial Infarction.
AB  - BACKGROUND: Residual ischemia detection after ST-segment elevation myocardial
      infarction (STEMI) during dobutamine stress echocardiography (DSE) using visual
      analysis is challenging. The aim of the present study was to investigate the
      feasibility and accuracy of two-dimensional speckle-tracking strain DSE to detect
      significant coronary artery disease (CAD) after STEMI. METHODS: First STEMI
      patients (n = 105; mean age, 60 +/- 11 years; 86% men) treated with primary
      percutaneous coronary intervention undergoing full-protocol DSE at 3 months and
      repeat coronary angiography within 1 year were retrospectively included. Using
      two-dimensional speckle-tracking echocardiography, segmental and global left
      ventricular peak longitudinal systolic strain (PLSS) at rest and peak stress and
      change (Delta) in PLSS were measured. Significant CAD was defined as detection of
      >70% diameter stenosis at coronary angiography. RESULTS: In total, 1,653 (93%)
      and 1,645 (92%) segments were analyzable at rest and peak stress, respectively.
      At follow-up, 38 patients (36%) showed significant angiographic CAD. These
      patients demonstrated greater worsening in global PLSS from rest to peak (-16.8
      +/- 0.5% to -12.6 +/- 0.5%) compared with patients without significant CAD (-16.6
      +/- 0.4% to -14.3 +/- 0.3%; group-stage interaction P < .001). The optimal cutoff
      of DeltaPLSS for the detection of significant CAD on receiver operating
      characteristic curve analysis was >=1.9% (area under the curve, 0.70;
      sensitivity, 87%; specificity, 46%; accuracy, 60%). Using a sentinel segment
      approach (apex, midposterior, and midinferior for the left anterior descending,
      left circumflex, and right coronary artery territories, respectively), larger
      segmental DeltaPLSS was also independently associated with significant CAD (odds
      ratio, 1.1; 95% CI, 1.1-1.2). CONCLUSIONS: Two-dimensional speckle-tracking
      echocardiographic strain analysis is feasible on DSE after STEMI and represents a
      promising new technique to detect significant angiographic CAD at follow-up.

PMID- 26307374
TI  - Differential left ventricular outflow tract remodeling and dynamics in aortic
      stenosis.
AB  - BACKGROUND: Left ventricular outflow tract (LVOT) geometry is variable and often
      elliptical, which can affect aortic valve area calculation in patients with
      aortic stenosis (AS). Specific differences in LVOT geometry and dynamics between
      patients with AS and normal control subjects have not been described. The aim of
      this study was to test the hypothesis that differences in LVOT geometry in
      patients with AS might relate to variable LVOT remodeling and stiffness relative
      to normal control subjects. METHODS: In 54 patients with severe AS and 33 control
      subjects without AS, LVOT geometry, dynamics, remodeling, and stiffness were
      assessed by three-dimensional transesophageal echocardiography. LVOT stiffness
      was measured by calculating the distensibility coefficient, defined as the
      percentage change in LVOT area relative to change in left ventricular pressure.
      LVOT remodeling was assessed by measuring the posterior LVOT wall thickness.
      Multivariate linear regression analysis was used to determine independent
      associations with peak systolic LVOT ellipticity. LVOT area by three-dimensional
      transesophageal echocardiographic planimetry was compared with areas obtained
      assuming circular or elliptical geometry. RESULTS: At end-diastole, LVOT geometry
      was similar between patients with AS and normal control subjects. In patients
      with AS, however, the percentage change in cross-sectional area (7.5% vs 14.7%, P
      < .001) from end-diastole to peak systole was lower compared with normal control
      subjects, while peak systolic ellipticity index was higher in patients with AS
      (1.18 vs 1.08, P < .001). Compared with control subjects, patients with AS had
      lower distensibility coefficients (4.7 +/- 1.9 * 10(4) vs 12.5 +/- 5.3 * 10(4) mm
      Hg(-1), P < .001) and higher posterior LVOT wall thickness (3.5 +/- 0.8 vs 2.3 +/
      0.5 mm, P < .001). In multivariate analysis, posterior LVOT wall thickness and
      distensibility coefficient were independently associated with peak systolic LVOT
      ellipticity index. LVOT area underestimation by transthoracic echocardiography
      was higher in patients with AS when assuming circular geometry (20% vs 12%, P =
      .001). CONCLUSIONS: The LVOT is less distensible and undergoes remodeling in
      severe AS. These changes lead to greater peak systolic ellipticity and greater
      LVOT cross-sectional area underestimation relative to normal control subjects.
      These findings have important implications for the assessment of AS severity.

PMID- 26307375
TI  - Riga-Fede disease in a child.
AB  - Riga-Fede disease (RFD) was initially described as a benign ulceration of the
      lingual frenum or tongue of infants, most commonly resulting from repetitive
      trauma by natal teeth. However, similar clinical manifestations can also be found
      in children with repetitive tongue-thrusting habits or certain neurological
      disorders. This report describes an unusual case of RFD in a 6-year-old Chinese
      boy. The lesion appeared as an ulcer on the anterior ventral surface of the
      child's tongue, and was caused by a repetitive tongue-thrusting habit. After
      eliminating the source of repetitive trauma and starting concurrent use of
      therapeutic drugs for 1 week, the lesion healed completely. 

PMID- 26307376
TI  - Which stroke patients gain most from intermittent pneumatic compression: further
      analyses of the CLOTS 3 trial.
AB  - BACKGROUND: The CLOTS 3 trial showed that intermittent pneumatic compression
      (IPC) reduced the risk of DVT and improved survival after stroke. AIMS: To
      provide additional information which may help clinicians target IPC on the most
      appropriate patients by exploring the variation in its effects on subgroups
      defined by predicted prognosis. METHODS: A multicentre, parallel group,
      randomized trial enrolled immobile acute stroke patients and allocated them to
      IPC or no IPC. The primary outcome was proximal DVT at 30 days. Secondary
      outcomes at six-months included survival, disability, quality of life, and
      hospital costs. We stratified patients into quintiles according to their
      predicted prognosis at randomization, based on the Six Simple Variable model.
      RESULTS: Between December 2008 and September 2012, we enrolled 2876 patients in
      94 UK hospitals. Patients with the best predicted outcome had the lowest absolute
      risk of proximal DVT (6.7%) and death by six-months (9.3%). Allocation to IPC had
      little effect on DVT, survival, disability, quality of life, hospital length of
      stay, or costs. In patients with the worst predicted outcomes, the overall risk
      of DVT and death was 16.0% and 51.3%, respectively. IPC reduced DVT (odds
      reduction 34%) and improved survival 17% and significantly increased length of
      stay and hospital costs. In the three intermediate quintiles, IPC reduced the
      odds of DVT (35-43%) and improved survival (11-13%). Disability and quality of
      life at six-months depended on baseline severity but was not influenced
      significantly by IPC. CONCLUSIONS: IPC appears to reduce the risk of DVT and
      probably improves survival in all immobile stroke patients, other than the fifth
      with the best prognosis. It therefore seems reasonable to recommend that IPC
      should be considered in all immobile stroke patients, but that the final decision
      should be based on a judgment about the individual's prognosis. In some, their
      prognosis for survival with an acceptable quality of life will be so poor that
      use of IPC might be considered futile, while at the other end of the spectrum,
      patients' risk of DVT, and of dying from VTE, may not be high enough to justify
      the modest cost and inconvenience of IPC use.

PMID- 26307377
TI  - Global Transcriptome Profiling of Developing Leaf and Shoot Apices Reveals
      Distinct Genetic and Environmental Control of Floral Transition and Inflorescence
      Development in Barley.
AB  - Timing of the floral transition and inflorescence development strongly affect
      yield in barley (Hordeum vulgare). Therefore, we examined the effects of
      daylength and the photoperiod response gene PHOTOPERIOD1 (Ppd-H1) on barley
      development and analyzed gene expression changes in the developing leaves and
      main shoot apices (MSAs) of barley by RNA sequencing. The daylength sensitivity
      of MSA development had two phases, floret primordia initiated under long and
      short days, whereas successful inflorescence development occurred only under long
      days. The transcripts associated with floral transition were largely regulated
      independently of photoperiod and allelic variation at Ppd-H1. The photoperiod-
      and Ppd-H1-dependent differences in inflorescence development and flower
      fertility were associated with the induction of barley FLOWERING LOCUS T
      orthologs: FT1 in leaves and FT2 in MSAs. FT1 expression was coregulated with
      transcripts involved in nutrient transport, carbohydrate metabolism, and cell
      cycle regulation, suggesting that FT1 might alter source-sink relationships.
      Successful inflorescence development correlated with upregulation of FT2 and
      transcripts related to floral organ development, phytohormones, and cell cycle
      regulation. Identification of photoperiod and stage-specific transcripts gives
      insights into the regulation of reproductive development in barley and provides a
      resource for investigation of the complexities of development and yield in
      temperate grasses. 

PMID- 26307378
TI  - HIGH CHLOROPHYLL FLUORESCENCE145 Binds to and Stabilizes the psaA 5' UTR via a
      Newly Defined Repeat Motif in Embryophyta.
AB  - The seedling-lethal Arabidopsis thaliana high chlorophyll fluorescence145
      (hcf145) mutation leads to reduced stability of the plastid tricistronic psaA
      psaB-rps14 mRNA and photosystem I (PSI) deficiency. Here, we genetically mapped
      the HCF145 gene, which encodes a plant-specific, chloroplast-localized, modular
      protein containing two homologous domains related to the polyketide cyclase
      family comprising 37 annotated Arabidopsis proteins of unknown function. Two
      further highly conserved and previously uncharacterized tandem repeat motifs at
      the C terminus, herein designated the transcript binding motif repeat (TMR)
      domains, confer sequence-specific RNA binding capability to HCF145. Homologous
      TMR motifs are often found as multiple repeats in quite diverse proteins of green
      and red algae and in the cyanobacterium Microcoleus sp PCC 7113 with unknown
      function. HCF145 represents the only TMR protein found in vascular plants.
      Detailed analysis of hcf145 mutants in Arabidopsis and Physcomitrella patens as
      well as in vivo and in vitro RNA binding assays indicate that HCF145 has been
      recruited in embryophyta for the stabilization of the psaA-psaB-rps14 mRNA via
      specific binding to its 5' untranslated region. The polyketide cyclase-related
      motifs support association of the TMRs to the psaA RNA, presumably pointing to a
      regulatory role in adjusting PSI levels according to the requirements of the
      plant cell. 

PMID- 26307379
TI  - The Interaction between Rice ERF3 and WOX11 Promotes Crown Root Development by
      Regulating Gene Expression Involved in Cytokinin Signaling.
AB  - Crown roots are the main components of the fibrous root system in rice (Oryza
      sativa). WOX11, a WUSCHEL-related homeobox gene specifically expressed in the
      emerging crown root meristem, is a key regulator in crown root development.
      However, the nature of WOX11 function in crown root development has remained
      elusive. Here, we identified a rice AP2/ERF protein, ERF3, which interacts with
      WOX11 and was expressed in crown root initials and during crown root growth.
      Functional analysis revealed that ERF3 was essential for crown root development
      and acts in auxin- and cytokinin-responsive gene expression. Downregulation of
      ERF3 in wox11 mutants produced a more severe root phenotype. Also, increased
      expression of ERF3 could partially complement wox11, indicating that the two
      genes functioned cooperatively to regulate crown root development. ERF3 and WOX11
      shared a common target, the cytokinin-responsive gene RR2. The expression of ERF3
      and WOX11 only partially overlapped, underlining a spatio-temporal control of RR2
      expression and crown root development. Furthermore, ERF3-regulated RR2 expression
      was involved in crown root initiation, while the ERF3/WOX11 interaction likely
      repressed RR2 during crown root elongation. These results define a mechanism
      regulating gene expression involved in cytokinin signaling during different
      stages of crown root development in rice. 

PMID- 26307380
TI  - Chlamydomonas Genome Resource for Laboratory Strains Reveals a Mosaic of Sequence
      Variation, Identifies True Strain Histories, and Enables Strain-Specific Studies.
AB  - Chlamydomonas reinhardtii is a widely used reference organism in studies of
      photosynthesis, cilia, and biofuels. Most research in this field uses a few dozen
      standard laboratory strains that are reported to share a common ancestry, but
      exhibit substantial phenotypic differences. In order to facilitate ongoing
      Chlamydomonas research and explain the phenotypic variation, we mapped the
      genetic diversity within these strains using whole-genome resequencing. We
      identified 524,640 single nucleotide variants and 4812 structural variants among
      39 commonly used laboratory strains. Nearly all (98.2%) of the total observed
      genetic diversity was attributable to the presence of two, previously
      unrecognized, alternate haplotypes that are distributed in a mosaic pattern among
      the extant laboratory strains. We propose that these two haplotypes are the
      remnants of an ancestral cross between two strains with ~2% relative divergence.
      These haplotype patterns create a fingerprint for each strain that facilitates
      the positive identification of that strain and reveals its relatedness to other
      strains. The presence of these alternate haplotype regions affects phenotype
      scoring and gene expression measurements. Here, we present a rich set of genetic
      differences as a community resource to allow researchers to more accurately
      conduct and interpret their experiments with Chlamydomonas. 

PMID- 26307381
TI  - Empirical Derivation and Validation of a Clinical Case Definition for
      Neuropsychological Impairment in Children and Adolescents.
AB  - Neuropsychological assessment aims to identify individual performance profiles in
      multiple domains of cognitive functioning; however, substantial variation exists
      in how deficits are defined and what cutoffs are used, and there is no
      universally accepted definition of neuropsychological impairment. The aim of this
      study was to derive and validate a clinical case definition rule to identify
      neuropsychological impairment in children and adolescents. An existing normative
      pediatric sample was used to calculate base rates of abnormal functioning on
      eight measures covering six domains of neuropsychological functioning. The
      dataset was analyzed by varying the range of cutoff levels [1, 1.5, and 2
      standard deviations (SDs) below the mean] and number of indicators of impairment.
      The derived rule was evaluated by bootstrap, internal and external clinical
      validation (orthopedic and traumatic brain injury). Our neuropsychological
      impairment (NPI) rule was defined as "two or more test scores that fall 1.5 SDs
      below the mean." The rule identifies 5.1% of the total sample as impaired in the
      assessment battery and consistently targets between 3 and 7% of the population as
      impaired even when age, domains, and number of tests are varied. The NPI rate
      increases in groups known to exhibit cognitive deficits. The NPI rule provides a
      psychometrically derived method for interpreting performance across multiple
      tests and may be used in children 6-18 years. The rule may be useful to
      clinicians and scientists who wish to establish whether specific individuals or
      clinical populations present within expected norms versus impaired function
      across a battery of neuropsychological tests.

PMID- 26307382
TI  - Tailoring the Two Dimensional Electron Gas at Polar ABO3/SrTiO3 Interfaces for
      Oxide Electronics.
AB  - The 2D electron gas at the polar/non-polar oxide interface has become an
      important platform for several novel oxide electronic devices. In this paper, the
      transport properties of a wide range of polar perovskite oxide ABO3/SrTiO3 (STO)
      interfaces, where ABO3 includes LaAlO3, PrAlO3, NdAlO3, NdGaO3 and LaGaO3 in both
      crystalline and amorphous forms, were investigated. A robust 4 unit cell (uc)
      critical thickness for metal insulator transition was observed for crystalline
      polar layer/STO interface while the critical thickness for amorphous ones was
      strongly dependent on the B site atom and its oxygen affinity. For the
      crystalline interfaces, a sharp transition to the metallic state (i.e.
      polarization catastrophe induced 2D electron gas only) occurs at a growth
      temperature of 515  degrees C which corresponds to a critical relative
      crystallinity of ~70 +/- 10% of the LaAlO3 overlayer. This temperature is
      generally lower than the metal silicide formation temperature and thus offers a
      route to integrate oxide heterojunction based devices on silicon. 

PMID- 26307383
TI  - Improving prognostication in childhood stroke.

PMID- 26307384
TI  - Sunitinib monotherapy instead of mitotane combination therapy for the treatment
      of refractory adrenocortical carcinoma.

PMID- 26307385
TI  - Capsule Commentary on McNeely et al., Validation of Self-Administered Single Item
      Screening Questions (SISQs) for Unhealthy Alcohol and Drug use in Primary Care
      Patients.

PMID- 26307386
TI  - Diagnostic Scheming.

PMID- 26307387
TI  - Industry Support of Medical Research: Important Opportunity or Treacherous
      Pitfall?
AB  - Pharmaceutical and device manufacturers fund more than half of the medical
      research in the U.S. Research funding by for-profit companies has increased over
      the past 20 years, while federal funding has declined. Research funding from for
      profit medical companies is seen as tainted by many academicians because of
      potential biases and prior misbehavior by both investigators and companies. Yet
      NIH is encouraging partnerships between the public and private sectors to enhance
      scientific discovery. There are instances, such as methods for improving drug
      adherence and post-marketing drug surveillance, where the interests of
      academician researchers and industry could be aligned. We provide examples of
      ethically performed industry-funded research and a set of principles and
      benchmarks for ethically credible academic-industry partnerships that could allow
      academic researchers, for-profit companies, and the public to benefit. 

PMID- 26307388
TI  - Capsule Commentary on Warner et al., Faculty Promotion and Attrition: the
      Importance of Coauthor Network Reach at an Academic Medical Center.

PMID- 26307389
TI  - The Role of Behavioral Health in Optimizing Care for Complex Patients in the
      Primary Care Setting.

PMID- 26307390
TI  - Cabergoline for Cushing's disease: A case report.

PMID- 26307391
TI  - HIF-2alpha regulates CDCP1 to promote PKCdelta-mediated migration in
      hepatocellular carcinoma.
AB  - Overexpression of CUB domain-containing protein 1 (CDCP1), a transmembrane
      glycoprotein and major substrate of Src family kinases (SFKs), always indicates
      unfavorable outcomes in various cancers. The characteristics of CDCP1 in
      hepatocellular carcinoma (HCC) have not been assessed. Most recently, CDCP1 was
      identified as a specific target gene of HIF-2alpha in clear cell renal carcinoma
      (CC-RCC). However, considering the role of HIF-2alpha in the progression of HCC
      is highly controversial, it is necessary to figure out whether HIF-2alpha and
      CDCP1 play a significant part in the metastasis of HCC. Our results showed that
      HIF-2alpha and CDCP1 were both induced by hypoxia, and the activation of CDCP1
      was HIF-2alpha dependent. CDCP1 was governed by HIF-2alpha at mRNA and protein
      levels in HCC cell lines. Moreover, knocking down of HIF-2alpha not only
      inhibited cell invasion but also impaired the expression of Tyr(311)
      phosphorylation of protein kinase Cdelta (PKCdelta) which is a downstream factor
      of CDCP1 and has been reported to induce malignant migration in various tumors.
      Analysis of human HCC samples showed a negative correlation of CDCP1 expression
      with disease-free survival, and CDCP1 was an independent prognostic factors of
      disease-free survival. Taken together, these data demonstrated that HIF-2alpha
      could promote HCC cell migration by regulating CDCP1, and targeting HIF-2alpha
      CDCP1-PKCdelta pathway might be effective to inhibit HCC metastasis. 

PMID- 26307393
TI  - Epigenetic downregulated ITGBL1 promotes non-small cell lung cancer cell invasion
      through Wnt/PCP signaling.
AB  - Integrin, beta-like 1 (ITGBL1), is a beta-integrin-related extracellular matrix
      protein which contains ten EGF-like repeats domain. Surprisingly, we screen
      Oncomine Database and found that ITGBL1 is more commonly downregulated in non
      small cell lung cancer (NSCLC) tissues, and the result reminds us to explore its
      significance in NSCLC. Thus, we retrieved DRUGSURV Database and found that
      downregulated ITGBL1 predicts a poor prognosis of patients. These results
      provided us the clues that ITGBL1 might be a tumor suppressor in NSCLC. However,
      the biological functions of ITGBL1 have not been reported to date. In the current
      study, we surprisingly found that knockdown of ITGBL1 in NSCLC cell lines could
      promote cancer cell migration and invasion. Furthermore, recombinant ITGBL1
      protein-treated cancer cell could inhibit cell migration and invasion. These
      results suggested that ITGBL1 plays a suppressive role in NSCLC progression. We
      further found that the downregulation of ITGBL1 might result from highly
      expressed miR-576-5p in NSCLC tissues, and the activity of Wnt/PCP signaling was
      enhanced when the level of ITGBL1 was inhibited. In conclusion, our results
      suggest that ITGBL1 is a novel tumor suppressor in NSCLC progression. 

PMID- 26307392
TI  - Malignant tumors of the uterine corpus: molecular background of their origin.
AB  - Tumors of the uterine corpus can be divided into two main groups: endometrial
      tumors and mesenchymal tumors. The former ones are common gynecological diseases,
      whereas malignant mesenchymal tumors, which behave in a much more aggressive way,
      are quite rare with a poorer prognosis. The most common type of endometrial
      tumors is endometrioid adenocarcinomas, and in case of mesenchymal tumors, these
      are carcinosarcomas, or leiomyosarcomas, if only clear types of tumors are taken
      into account. The objective of this article is to review molecular-genetic
      abnormalities associated with tumorigenesis of both types of tumors, with focus
      on the most aggressive forms. This view includes a different expression pattern
      of genes, usually aberrant in cases of uterine cancer that can arise due to
      epigenetic modifications, mostly hypermethylation of promoters or microRNA
      (miRNA)'s interference with concrete genes. Furthermore, clinical predispositions
      of tumorigenesis, involving hormonal factors, age, and ethnicity, are also
      mentioned.

PMID- 26307394
TI  - Evaluation of GWAS-identified SNPs at 6p22 with neuroblastoma susceptibility in a
      Chinese population.
AB  - Previous genome-wide association studies (GWASs) have reported that three single
      nucleotide polymorphisms (SNPs) (rs6939340 A>G, rs4712653 T>C, and rs9295536 C>A)
      located at 6p22 locus were associated with neuroblastoma susceptibility for
      Caucasian descent. We conducted this hospital-based case-control study with 201
      neuroblastoma patients and 531 controls to investigate the association between
      these three SNPs in the FLJ22536 gene with neuroblastoma susceptibility in the
      Chinese Han population. The odds ratio (OR) and 95 % confidence interval (CI)
      were calculated to estimate the strength of the association using unconditional
      logistic regression model. We found that the rs6939340 A allele carriers were
      associated with significantly decreased neuroblastoma susceptibility (AG vs. GG:
      adjusted OR = 0.54, 95 % CI = 0.38-0.77; AA vs. GG: adjusted OR = 0.49, 95 % CI =
      0.25-0.93; and AA/AG vs. GG: adjusted OR = 0.53, 95 % CI = 0.38-0.74) after
      adjustment for age and gender. The protective association between variant allele
      and neuroblastoma susceptibility was also observed for the rs4712653 and
      rs9295536 polymorphisms. Moreover, we found that subjects carrying one or more
      protective genotypes had a much lower neuroblastoma susceptibility than non
      carriers (adjusted OR = 0.60, 95 % CI = 0.43-0.83). Our study verified that the
      associations between all of the three SNPs in the 6p22 locus are associated with
      neuroblastoma susceptibility in the Chinese subjects. Further prospective
      multicenter studies with different ethnicities and larger sample size are needed
      to validate our findings. 

PMID- 26307395
TI  - Breast cancer circulating biomarkers: advantages, drawbacks, and new insights.
AB  - As of today, the level of individualization of cancer therapies has reached a
      level that 20 years ago would be considered visionary. However, most of the
      diagnostic, prognostic, and therapy-predictive procedures which aim to improve
      the overall level of personalization are based on the evaluation of tumor tissue
      samples, therefore requiring surgical operations with consequent low compliance
      for patients and high costs for the hospital. Hence, the research of a panel of
      circulating indicators which may serve as source of information about tumor
      characteristics and which may be obtainable by a simple withdrawal of peripheral
      blood today represents a growing field of interest. This review aims to
      objectively summarize the characteristics of the currently available breast
      cancer circulating biomarkers, also providing an overview about the multitude of
      novel potential soluble predictors which are still under evaluation.
      Specifically, the usefulness of a so-called "liquid biopsy" will be discussed in
      terms of improvements of diagnosis, prognosis, and therapy-prediction, but an
      overview will be given also on the potentiality of the molecular characterization
      arising from the isolation of circulating biomarkers and cells. Although this
      review will focus on the specific case of the breast, in the future liquid
      biopsies will hopefully be available for virtually any type of neoplasms.

PMID- 26307397
TI  - A novel phenotype of a hepatocyte nuclear factor homeobox A (HNF1A) gene
      mutation, presenting with neonatal cholestasis.

PMID- 26307396
TI  - Upregulation of HOXB7 promotes the tumorigenesis and progression of gastric
      cancer and correlates with clinical characteristics.
AB  - Several examples of aberrant homeobox gene expression have been found across a
      range of cancers, and it is also confirmed that homeobox genes play a critical
      roles in tumorigenesis and progression. Notwithstanding homeobox B7 (HOXB7) has
      been documented that its deregulation promotes carcinogenesis and development in
      gastrointestinal tract, its function in gastric cancer has not been investigated.
      In this study, HOXB7 expression was examined to be distinctly upregulated in
      gastric carcinoma GC cell lines and in the tumor relative to normal gastric
      tissue. High HOXB7 expression was correlated with tumor differentiation (P =
      0.025) and TNM stage (P = 0.008). HOXB7 knockdown in BGC-823 and SGC-7901
      resulted in decreased migration and invasion with alteration of epithelial
      mesenchymal transition (EMT) proteins and influenced proliferation, apoptosis,
      and cell cycle. Furthermore, complementary DNA (cDNA) microarray, qPCR, and
      Western blotting were performed to explore potential downstream target genes of
      HOXB7. HOXB7 is generally overexpressed in GC, associated with patient clinical
      characteristics, and specifically promotes GC cell malignant biological
      properties through PIK3R3/AKT signaling pathways, indicating HOXB7 as a causal
      factor in promoting tumor progression. 

PMID- 26307398
TI  - Collagen and tissue turnover as a function of age: Implications for fibrosis.
AB  - BACKGROUND & AIMS: The extracellular matrix (ECM) is the backbone of all tissues.
      It is a complex grid consisting of multiple structural proteins which each play a
      vital role for the function and maintenance of normal tissue function. In
      development and growth, tissue is being formed and elaborated (tissue modeling),
      while in adult life, tissues are being maintained and remodeled. These processes
      involve likely different mechanisms. During tissue modeling and remodeling, small
      fragments of proteins are released into the circulation, where they may be used
      as biomarkers for tissue turnover. The aim of the study was to investigate ECM
      turnover in rodents as a function of age. METHODS: Serum of rats of 1, 2, 3, 4,
      5, 6, 10 and 12months of age was profiled for 15 markers of ECM turnover,
      including: fragments of type I, II, III, IV, V and VI collagen formation (P1NP,
      P4NP-7S, Pro-C5, Pro-C6) and degradation (C1M, C2M, C2M-beta, C3M, C4M, C5M,
      C6M); biglycan (BGM) and elastin (ELM7) degradation; and the type I and II
      collagen telopeptides CTX-I and CTX-II. RESULTS: Type I and II collagen turnover
      was up to 93% and 97% downregulated in old (one year) compared to young (one
      month) old animals (p<0.0001), while type IV and V collagen and biglycan turnover
      was upregulated 2.5-, 2- and 2-fold, respectively (p<0.0001). Type III and VI
      collagen and elastin turnover was not influenced significantly by age.
      CONCLUSIONS: ECM turnover rates were consistently different in young vs. old
      animals, up to 30 fold. This appears to be due to body growth, a different ECM
      composition and a higher regenerative capability of connective tissues in young
      vs. old animals. These changes have to be accounted for in translational science.
      Both in measuring serum levels of ECM biomarkers and in the development of
      therapies to speed up wound healing or inhibit fibrogenesis.

PMID- 26307399
TI  - A paradigm shift in imaging biomarkers in neovascular age-related macular
      degeneration.
AB  - Neovascular age-related macular degeneration (AMD) has undergone substantial
      break-throughs in diagnostic as well as therapeutic respect, with optical
      coherence tomography (OCT) allowing to identify disease morphology in great
      detail, and intravitreal anti-vascular endothelial growth factor therapy
      providing unprecedented benefit. However, these two paths have yet not been
      combined in an optimal way, real-world outcomes are inferior to expectations, and
      disease management is largely inefficient in the real-world setting. This dilemma
      can be solved by identification of valid biomarkers relevant for visual function,
      disease activity and prognosis, which can provide solid guidance for therapeutic
      management on an individual level as well as on the population base. Qualitative
      and quantitative morphological features obtained by advanced OCT provide novel
      insight into exudative and degenerative stages of neovascular AMD. However,
      conclusions from structure/function correlations evolve differently from previous
      paradigms. While central retinal thickness was used as biomarker for guiding
      retreatment management in clinical trials and practice, fluid localization in
      different compartments offers superior prognostic value: Intraretinal cystoid
      fluid has a negative impact on visual acuity and is considered as degenerative
      when persisting through the initial therapeutic interval. Subretinal fluid is
      associated with superior visual benefit and a lower rate of progression towards
      geographic atrophy. Detachment of the retinal pigment epithelium was identified
      as most pathognomonic biomarker, often irresponsive to therapy and responsible
      for visual decline during a pro-re-nata regimen. Alterations of neurosensory
      tissue are usually associated with irreversible loss of functional elements and a
      negative prognosis. Novel OCT technologies offer crucial insight into
      corresponding changes at the level of the photoreceptor--retinal pigment
      epithelial--choriocapillary unit, identifying the biological limits of
      therapeutic interventions. To optimally benefit from high-resolution multi-modal
      imaging, an integrated analysis of all functional and structural features is
      required involving reliable automated algorithms and computational data analyses.
      Using innovative analysis methods, retinal biomarkers can be used to provide
      efficient personalized therapy for the individual patient, predictive disease-
      and population-based models for large-scale management and identifying promising
      targets for the development of novel therapeutic strategies.

PMID- 26307401
TI  - Robotic laparoendoscopic single site radical hysterectomy with sentinel lymph
      node mapping and pelvic lymphadenectomy for cervical cancer.

PMID- 26307400
TI  - The prescription or proscription of exercise in endometrial cancer care.
AB  - OBJECTIVE: To determine the proportion of endometrial cancer patients who can be
      safely prescribed community/home based unsupervised exercise. A better
      understanding of the physical dysfunction secondary to comorbidities among
      endometrial cancer patients would assist clinicians in delineating which patients
      to send to medically-based supervised rehabilitation versus a community/home
      based unsupervised exercise program. METHODS: A literature review identified
      health issues which could impede patients from successfully completing an
      unsupervised exercise program after a cancer diagnosis. The charts of 479
      endometrial cancer patients treated between 2006 and 2010 were reviewed to
      determine the health status at the time of diagnosis and the type and percentage
      of health-issues that could preclude an unsupervised exercise program in this
      population. Univariable modeling and multivariable modeling were used to evaluate
      the association of demographic, cancer-related characteristics and clinical
      variables with ability to participate in unsupervised exercise. RESULTS: We
      determined that 14.2% of endometrial cancer patients were able to exercise
      without supervision based on their health status at the time of diagnosis. After
      excluding common comorbidities (hypertension, diabetes and morbid obesity) from
      the identified health-issues, the proportion increased to 20.5%. Older at
      diagnosis (P=0.007) and higher BMI (P<0.001) are more likely to exclude patients
      from community/home based unsupervised exercise program. CONCLUSIONS: Only 14.2%
      to 20.5% of endometrial cancer patients were deemed able to exercise without
      supervision based on their health status at diagnosis. Our data suggest that
      approximately 80% of endometrial cancer patients would benefit from a referral to
      a medically-based supervised exercise program.

PMID- 26307402
TI  - Patterns of care, predictors and outcomes of chemotherapy for uterine
      carcinosarcoma: a National Cancer Database analysis.
AB  - OBJECTIVE: Evaluate rates of chemotherapy and radiotherapy delivery in the
      treatment of uterine carcinosarcoma, and compare clinical outcomes of treated and
      untreated patients. METHODS: The National Cancer Database was queried to identify
      patients diagnosed with uterine carcinosarcoma between 2003 and 2011. The impact
      of chemotherapy on survival was analyzed using the Kaplan-Meier method. Factors
      predictive of outcome were compared using the Cox proportional hazards model.
      RESULTS: A total of 10,609 patients met study eligibility criteria. Stages I, II,
      III, and IV disease accounted for 2997 (28.2%), 642 (6.1%), 2037 (19.2%), and
      1316 (12.4%) of the study population, respectively. Most patients (91.0%)
      underwent definitive surgery, and lymphadenectomy was performed in 68.7% of the
      patients. Chemotherapy was administered in 2378 (22.4%) patients, radiotherapy to
      2196 (20.7%), adjuvant chemo-radiation to 1804 (17.0%), and 4231 (39.9%) of women
      did not received adjuvant therapy. Utilization of chemotherapy became more
      frequent over time. Over the entire study period, after adjusting for race,
      period of diagnosis, facility location, facility type, insurance provider, stage,
      age, treatment modality, lymph node dissection, socioeconomic status, and
      comorbidity index, there was an association between treatment modality and
      survival. The lowest hazard ratio observed was in patients that received chemo
      radiation. The strongest quantitative predictor of death was stage at the time of
      diagnosis. In addition, surgical treatment, lymph node dissection, most recent
      time-periods, lower comorbidity index, and higher socioeconomic status were
      associated with improved survival. CONCLUSION: The overall rates of chemotherapy
      use have increased over time. Adjuvant chemotherapy and chemo-radiation were
      associated with improved survival.

PMID- 26307403
TI  - Site-Selective Reactions with Peptide-Based Catalysts.
AB  - The problem of catalyst-controlled site-selectivity can potentially require a
      catalyst to overcome energetic barriers larger than those associated with
      enantioselective reactions. This challenge is a signature of substrates that
      present reactive sites that are not of equivalent reactivity. Herein we present a
      narrative of our laboratory's efforts to overcome this challenge using peptide
      based catalysts. We highlight the interplay between understanding the inherent
      reactivity preferences of a given target molecule and the development of
      catalysts that can overcome intrinsic preferences embedded within a substrate. 

PMID- 26307405
TI  - Identifying environmental versus phylogenetic correlates of behavioural ecology
      in gibbons: implications for conservation management of the world's rarest ape.
AB  - BACKGROUND: For conservation of highly threatened species to be effective, it is
      crucial to differentiate natural population parameters from atypical behavioural,
      ecological and demographic characteristics associated with human disturbance and
      habitat degradation, which can constrain population growth and recovery.
      Unfortunately, these parameters can be very hard to determine for species of
      extreme rarity. The Hainan gibbon (Nomascus hainanus), the world's rarest ape,
      consists of a single population of c.25 individuals, but intensive management is
      constrained by a limited understanding of the species' expected population
      characteristics and environmental requirements. In order to generate a more
      robust evidence-base for Hainan gibbon conservation, we employed a comparative
      approach to identify intrinsic and extrinsic drivers of variation in key
      ecological and behavioural traits (home range size, social group size, mating
      system) across the Hylobatidae while controlling for phylogenetic non
      independence. RESULTS: All three studied traits show strong phylogenetic signals
      across the Hylobatidae. Although the Hainan gibbon and some closely related
      species have large reported group sizes, no observed gibbon group size is
      significantly different from the values expected on the basis of phylogenetic
      relationship alone. However, the Hainan gibbon and two other Nomascus species (N.
      concolor, N. nasutus) show home range values that are higher than expected
      relative to all other gibbon species. Predictive models incorporating
      intraspecific trait variation but controlling for covariance between population
      samples due to phylogenetic relatedness reveal additional environmental and
      biological determinants of variation in gibbon ranging requirements and social
      structure, but not those immediately associated with recent habitat degradation.
      CONCLUSIONS: Our study represents the first systematic assessment of behavioural
      and ecological trait patterns across the Hylobatidae using recent approaches in
      comparative analysis. By formally contextualising the Hainan gibbon's observed
      behavioural and ecological characteristics within family-wide variation in
      gibbons, we are able to determine natural population parameters expected for this
      Critically Endangered species, as well as wider correlates of variation for key
      population characteristics across the Hylobatidae. This approach reveals key
      insights with a direct impact on future Hainan gibbon conservation planning, and
      demonstrates the usefulness of the comparative approach for informing management
      of species of conservation concern.

PMID- 26307404
TI  - Phosphatase and tensin homolog (PTEN) in antigen-presenting cells controls Th17
      mediated autoimmune arthritis.
AB  - INTRODUCTION: Autoreactive T cells are a central element in many systemic
      autoimmune diseases. The generation of these pathogenic T cells is instructed by
      antigen-presenting cells (APCs). However, signaling pathways in APCs that drive
      autoimmune diseases, such as rheumatoid arthritis, are not understood. METHODS:
      We measured phenotypic maturation, cytokine production and induction of T cell
      proliferation of APCs derived from wt mice and mice with a myeloid-specific
      deletion of PTEN (myeloid PTEN(-/-)) in vitro and in vivo. We induced collagen
      induced arthritis (CIA) and K/BxN serum transfer arthritis in wt and myeloid
      specific PTEN(-/-) mice. We measured the cellular composition of lymph nodes by
      flow cytometry and cytokines in serum and after ex vivo stimulation of T cells.
      RESULTS: We show that myeloid-specific PTEN(-/-) mice are almost protected from
      CIA. Myeloid-specific deletion of PTEN leads to a significant reduction of
      cytokine expression pivotal for the induction of systemic autoimmunity such as
      interleukin (IL)-23 and IL-6, leading to a significant reduction of a Th17 type
      of immune response characterized by reduced production of IL-17 and IL-22. In
      contrast, myeloid-specific PTEN deficiency did not affect K/BxN serum transfer
      arthritis, which is independent of the adaptive immune system and solely depends
      on innate effector functions. CONCLUSIONS: These data demonstrate that the
      presence of PTEN in myeloid cells is required for the development of CIA.
      Deletion of PTEN in myeloid cells inhibits the development of autoimmune
      arthritis by preventing the generation of a pathogenic Th17 type of immune
      response.

PMID- 26307406
TI  - Natural rubber latex coated with calcium phosphate for biomedical application.
AB  - Natural rubber latex (NRL) is a flexible biomembrane that possesses angiogenic
      properties and has recently been used for guided bone regeneration, enhancing
      healing without fibrous tissue, allergies or rejection. Calcium phosphate (Ca/P)
      ceramics have chemical, biological, and mechanical properties similar to mineral
      phase of bone, and ability to bond to the host tissue, although it can disperse
      from where it is applied. Therefore, to create a composite that could enhance the
      properties of both materials, NRL biomembranes were coated with Ca/P. NRL
      biomembranes were soaked in 1.5 times concentrated SBF solution for seven days,
      avoiding the use of high temperatures. SEM showed that Ca/P has been coated in
      NRL biomembrane, XRD showed low crystallinity and FTIR showed that is the
      carbonated type B. Furthermore, hemolysis of erythrocytes, quantified
      spectrophotometrically using materials (Ca/P, NRL, and NRL + Ca/P) showed no
      hemolytic effects up to 0.125 mg/mL (compounds and mixtures), indicating no
      detectable disturbance of the red blood cell membranes. The results show that the
      biomimetic is an appropriate method to coat NRL with Ca/P without using high
      temperatures, aiming a new biomembrane to improve guided bone regeneration. 

PMID- 26307408
TI  - Vivien Theodore Thomas (1910-1985): An African-American laboratory technician who
      went on to become an innovator in cardiac surgery.
AB  - Vivien Theodore Thomas (1910-1985) was an African-American laboratory technician
      and instructor of surgery at Johns Hopkins University, Baltimore. He was born as
      the grandson of a slave in Lousiana, working as a carpenter and subsequently as a
      laboratory technician after the great depression and the loss of his savings
      derailed his plans to become a doctor. In his role as a laboratory technician, he
      overcame challenging personal circumstances to become an innovator in paediatric
      cardiac surgery, despite having no formal college education. He played an
      important role in assisting Alfred Blalock and Helen Taussig in the development
      of the 'Blalock-Taussig' shunt, a procedure used to improve the survival of
      children with cyanotic congenital heart defects. He also contributed to major
      breakthroughs in research covering a spectrum of disorders such as traumatic
      shock, coarctation of the aorta and transposition of the great arteries. He acted
      as a teacher and mentor to a generation of surgical residents and technicians who
      went on to become leaders in their field across the USA. A television film based
      on his life was premiered by HBO in 2004 titled 'Something the Lord made'.

PMID- 26307407
TI  - TRIM32 modulates pluripotency entry and exit by directly regulating Oct4
      stability.
AB  - Induced pluripotent stem cells (iPSCs) have revolutionized the world of
      regenerative medicine; nevertheless, the exact molecular mechanisms underlying
      their generation and differentiation remain elusive. Here, we investigated the
      role of the cell fate determinant TRIM32 in modulating such processes. TRIM32 is
      essential for the induction of neuronal differentiation of neural stem cells by
      poly-ubiquitinating cMyc to target it for degradation resulting in inhibition of
      cell proliferation. To elucidate the role of TRIM32 in regulating somatic cell
      reprogramming we analysed the capacity of TRIM32-knock-out mouse embryonic
      fibroblasts (MEFs) in generating iPSC colonies. TRIM32 knock-out MEFs produced a
      higher number of iPSC colonies indicating a role for TRIM32 in inhibiting this
      cellular transition. Further characterization of the generated iPSCs indicated
      that the TRIM32 knock-out iPSCs show perturbed differentiation kinetics.
      Additionally, mathematical modelling of global gene expression data revealed that
      during differentiation an Oct4 centred network in the wild-type cells is replaced
      by an E2F1 centred network in the TRIM32 deficient cells. We show here that this
      might be caused by a TRIM32-dependent downregulation of Oct4. In summary, the
      data presented here reveal that TRIM32 directly regulates at least two of the
      four Yamanaka Factors (cMyc and Oct4), to modulate cell fate transitions. 

PMID- 26307409
TI  - The afterlife of Laurence Sterne (1713-1768): Body snatching, dissection and the
      role of Cambridge anatomist Charles Collignon.
AB  - This paper aims to highlight the practice of body snatching from graves in the
      1700s for the purpose of providing corpses for anatomical dissection, and for
      stocking anatomy museums. To do this, we examine the exhumation and dissection of
      the famous eighteenth-century novelist Laurence Sterne and explore the
      involvement of Charles Collignon, Professor of Anatomy at the University of
      Cambridge. We also show that osteological and cut-mark analysis of a skull
      purported to be that of Sterne, currently housed in the Duckworth Collection at
      Cambridge, provides the key to solving the mystery surrounding why Sterne was
      resurrected.

PMID- 26307410
TI  - From glanders to globulins: A study in comparative medicine.
AB  - The anti-globulin test was described in 1945, and ever since has been synonymous
      with the lead author, Robin Coombs, a young veterinary surgeon, at that time
      embarking on a career in immunological research. This was marked by a number of
      important contributions in the field, including the description and
      categorisation of hypersensitivity reactions, co-authored with Philip Gell.
      Together they wrote the classical text, Clinical Aspects of Immunology, which has
      been updated and republished over the ensuing 50 years. Although Robin Coombs is
      best remembered for his contributions to medical immunology, he made a number of
      significant early advances in the field of veterinary immunology.

PMID- 26307411
TI  - Creativity and mood disorders: The enigmatic case of Isaak Il'ich Levitan (1860
      1900).
AB  - Isaak Levitan (1860-1900) was one of Russia's most influential landscape artists.
      He lived a very short life, only 40 years, but left more than 1000 paintings. He
      suffered from mood fluctuations, and died as a result of serious heart disease.
      After an introduction related to the issue of creativity and mental disorders, a
      short biography of Levitan's life is outlined, followed by some examples of his
      mood and behavior. A section on the mood's reflection in Levitan's professional
      work is followed by a description of his romantic loves and disappointments and
      his relationship with his contemporary Russian, the writer Anton Chekhov.

PMID- 26307412
TI  - Centennial ties: Harvey Cushing (1869-1939) and William Osler (1849-1919) on
      Andreas Vesalius (1514-1564).
AB  - Andreas Vesalius is often regarded as the founding father of modern anatomical
      study. The quincentennial anniversary of his birth - 31 December 2014 - has been
      very widely commemorated, and it is the purpose of this article to contrast these
      celebrations with what happened during the Vesalius quatercentenary year of 1914.
      More specifically, we look at how Vesalius was perceived a century ago by
      examining his influence on two of western medicine's most iconic gentlemen -
      Harvey Williams Cushing (1869-1939) and his larger than life mentor, Sir William
      Osler (1849-1919).

PMID- 26307413
TI  - Lest we forget: Edith Cavell 1865-1915.

PMID- 26307414
TI  - Who should Decide for the Unrepresented?
AB  - Unrepresented patients lack the capacity to make medical decisions for
      themselves, have no clear documentation of preferences for medical treatment, and
      have no surrogate decision maker or obvious candidate for that role. There is no
      consensus about who should serve as the decision maker for these patients,
      particularly regarding whether to continue or to limit life-sustaining treatment.
      Several authors have argued that ethics committees should play this role rather
      than the patient's treating physician, a common current default. We argue that
      concerns about the adequacy of physicians as surrogates are either empirically
      unfounded or apply equally to ethics committees. We suggest that physicians
      should be the primary decision maker for the unrepresented because of their
      fiduciary duties toward their patients. As part of the process of fulfilling
      these duties, they should seek the advice of third parties such as ethic
      committees; but final end-of-life decision-making for the unrepresented should
      rest with the treating physician. 

PMID- 26307415
TI  - Catheter securement systems: comparison of two investigational devices to a
      sutureless securement device, a securement dressing, and sutures in a pig model.
AB  - BACKGROUND: Catheter securement is critical for the success of infusion therapy
      and to prevent complications. Our purpose was to compare the strength of catheter
      securement achieved with two investigational adhesive securement devices to two
      securement products and also to sutures using an in vivo animal model. METHODS:
      Twenty-five live pigs were prepared for aseptic abdominal surgery. Four central
      venous catheters were inserted per animal into the epigastric veins and secured
      with four of the five securement systems studied, following a balanced incomplete
      randomized block design. A peak axial pull force test method was used to measure
      the force required to dislodge the catheter 1 cm from the insertion site and/or
      cause failure of the device and/or dressing. This pull test was done 10 min after
      device application, per constraints of the animal model. Comparison analysis was
      carried out using a mixed effects model with pig, sample, and sample location as
      factors. Non-inferiority testing was carried out using 95 % confidence intervals
      with a margin of 4.52 N or 1 lb (454 g). Tukey's method was used to adjust for
      multiple pairwise comparisons. RESULTS: Results showed that the two
      investigational devices displayed the highest mean peak axial pull forces (40-41
      N) and were significantly better than sutures (28 N, p < 0.0001) and the
      securement dressing (17 N, p < 0.0001) and non-inferior to the securement device
      (37 N) in this test. The securement device required a higher mean peak axial pull
      force than sutures (p = 0.0007) and the securement dressing (p < 0.0001) for
      failure to occur. Finally, there was also a statistical difference between
      sutures and the securement dressing, with sutures requiring a higher mean peak
      axial pull force for catheter dislodgement than the securement dressing (p <
      0.0001). CONCLUSION: The two investigational devices appear to be a promising
      alternative for catheter securement, superior to sutures and the securement
      dressing, and non-inferior to the securement device.

PMID- 26307416
TI  - Genetic diversity comparison of the DQA gene in European rabbit (Oryctolagus
      cuniculus) populations.
AB  - The European rabbit (Oryctolagus cuniculus) natural populations within the
      species native region, the Iberian Peninsula, are considered a reservoir of
      genetic diversity. Indeed, the Iberia was a Pleistocene refuge to the species and
      currently two subspecies are found in the peninsula (Oryctolagus cuniculus
      cuniculus and Oryctolagus cuniculus algirus). The genes of the major
      histocompatibility complex (MHC) have been substantially studied in wild
      populations due to their exceptional variability, believed to be pathogen driven.
      They play an important function as part of the adaptive immune system affecting
      the individual fitness and population viability. In this study, the MHC
      variability was assessed by analysing the exon 2 of the DQA gene in several
      European rabbit populations from Portugal, Spain and France and in domestic
      breeds. Twenty-eight DQA alleles were detected, among which 18 are described for
      the first time. The Iberian rabbit populations are well differentiated from the
      French population and domestic breeds. The Iberian populations retained the
      higher allelic diversity with the domestic breeds harbouring the lowest; in
      contrast, the DQA nucleotide diversity was higher in the French population.
      Signatures of positive selection were detected in four codons which are putative
      peptide-binding sites and have been previously detected in other mammals. The
      evolutionary relationships showed instances of trans-species polymorphism.
      Overall, our results suggest that the DQA in European rabbits is evolving under
      selection and genetic drift. 

PMID- 26307417
TI  - Inhibition of neuraminidase by Ganoderma triterpenoids and implications for
      neuraminidase inhibitor design.
AB  - Neuraminidase (NA) inhibitors are the dominant antiviral drugs for treating
      influenza in the clinic. Increasing prevalence of drug resistance makes the
      discovery of new NA inhibitors a high priority. Thirty-one triterpenoids from the
      medicinal mushroom Ganoderma lingzhi were analyzed in an in vitro NA inhibition
      assay, leading to the discovery of ganoderic acid T-Q and TR as two inhibitors of
      H5N1 and H1N1 NAs. Structure-activity relationship studies revealed that the
      corresponding triterpenoid structure is a potential scaffold for the design of NA
      inhibitors. Using these triterpenoids as probes we found, through further in
      silico docking and interaction analysis, that interactions with the amino-acid
      residues Arg292 and/or Glu119 of NA are critical for the inhibition of H5N1 and
      H1N1. These findings should prove valuable for the design and development of NA
      inhibitors. 

PMID- 26307418
TI  - Characterization of prefrontal cortex microstructure and antioxidant status in a
      rat model of neurodegeneration induced by aluminium chloride and multiple low
      dose streptozotocin.
AB  - Diabetes mellitus (DM) is a risk factor for Alzheimer's disease (AD), and several
      individuals with AD are diabetic. Most non-transgenic animal models of AD make
      use of oral treatment with aluminium chloride (AlCl(3)) to induce brain lesions
      pathognomonic of the disease. Moreover, streptozotocin (STZ) can induce
      pathological features of either AD or DM depending on the mode of treatment. In
      the present study, we characterised prefrontal microanatomy and antioxidant
      defence system in a rat model of AD confounded by DM, with the objective of
      assessing the suitability of this model in the study of sporadic AD with DM co
      morbidity. Adult Wistar rats were randomly assigned to receive either
      intraperitoneal STZ (30 mg/kg/day for 3 days; to induce DM), oral AlCl(3) (500
      mg/kg/day for 4 weeks; to induce some brain lesions characteristic of AD); or
      both STZ and AlCl(3) (to induce AD with DM co-morbidity). Untreated rats served
      as controls. During treatment, blood glucose levels and body weights were
      evaluated repeatedly in all rats. At euthanasia, prefrontal cortex was
      homogenized in phosphate buffer solution and the supernatants assayed for some
      antioxidant enzymes (catalase, CAT; superoxide dismutase, SOD; and reduced
      glutathione, GSH). Moreover, following perfusion-fixation of the brain, frontal
      lobes were processed by the haematoxylin and eosin (H&E) or Congo red technique.
      Our findings showed that in rats co-administered AlCl(3) and STZ (AD + DM rats),
      prefrontal levels of GSH reduced significantly (p < 0.05), while reductions in
      SOD and CAT were not significant (p > 0.05) compared with the controls. Moreover,
      in this model of AD with DM co-morbidity, extensive neuronal cell loss was
      observed in the prefrontal cortex, but Congophilic deposits were not present. The
      neurodegenerative lesions and antioxidant deficits characteristic of this AlCl(3)
      + STZ (AD + DM) rat model were more pronounced than similar lesions associated
      with mono-treatment with either STZ (DM) or AlCl(3) (AD) alone; and this makes
      the AlCl(3) + STZ model a suitable option for the study of neurodegenerative
      diseases (such as AD) with DM co-morbidity.

PMID- 26307420
TI  - Weight loss outcomes among patients referred after primary bariatric procedure.
AB  - BACKGROUND: Bariatric patients may not always obtain long-term care by their
      primary surgeon. Our aim was to evaluate weight loss outcomes in patients who had
      surgery elsewhere. METHODS: We conducted a retrospective analysis. Postreferral
      management included nonsurgical, revision, or conversion. Primary outcomes were
      percent excess weight loss (%EWL) overall, according to original operation, and
      based on postreferral management. RESULTS: Between 2001 and 2013, there were 569
      patients. Mean follow-up was 3.1 years. Management was 42% nonsurgical, 41%
      revision, and 17% conversion. Overall, mean %EWL was 45.3%. Based on original
      surgery type, %EWL was 41.2% for adjustable gastric banding vs 58.3% for Roux-en
      Y gastric bypass (P <= .0001). Management affected %EWL (41.2% nonsurgical vs
      45.3% revision vs 55.1% conversion, P <= .0001). CONCLUSIONS: Patients referred
      after bariatric surgery can achieve satisfactory weight loss. This differs based
      on surgery type and management strategy.

PMID- 26307419
TI  - Altered metal metabolism in patients with HCV-related cirrhosis and hepatic
      encephalopathy.
AB  - Dysfunctional metal homeostasis contributes to oxidative stress and neuronal
      damage. These have been implicated in hepatic encephalopathy pathogenesis. To
      investigate whether altered metal metabolism is associated with hepatic
      encephalopathy. Twenty-one controls and 34 HCV-cirrhotic patients (ENC/NEC
      patients according to presence/absence of previous overt episodes of hepatic
      encephalopathy) and a control group were studied. Serum iron, copper,
      ceruloplasmin, ceruloplasmin activity, transferrin, and ceruloplasmin/transferrin
      ratio were determined. Neuropsychological tests were performed by the repeatable
      battery of neuropsychological status. Magnetic resonance assessed basal ganglia
      volumes and metal deposition (pallidal index and T2*). Cirrhotic patients
      performed worse than controls at cognitive tests, especially ENC patients,. At
      biochemical analysis copper concentrations, ceruloplasmin activity and
      transferrin levels were lower in ENC than in NEC patients and controls (p < 0.05
      and p < 0.01, respectively). Ceruloplasmin/transferrin ratio was higher in ENC
      compared to NEC patients (p < 0.05), and controls (p < 0.01). By brain magnetic
      resonance, ENC patients showed reduced caudate and globus pallidus volumes
      compared to controls (p < 0.05), and ENC and NEC patients an increased pallidal
      index compared to controls (p < 0.01). In ENC patients, ceruloplasmin activity
      correlated with caudate volume and pallidal index (rho = 0.773 and rho = -0.683,
      p < 0.05). Altered metal metabolism likely contributes to cirrhotic hepatic
      encephalopathy.

PMID- 26307421
TI  - Morbidity and mortality of hepatectomy for benign liver tumors.
AB  - BACKGROUND: This study compared the morbidity and mortality following hepatectomy
      for benign liver tumors and hepatic metastases. METHODS: This retrospective
      cohort study compared patients who underwent hepatectomy for benign liver tumors
      and metastases reported to National Surgical Quality Improvement Program between
      2005 and 2011. RESULTS: A total of 5,542 patients underwent hepatectomy: 1,164
      (21%) for benign and 4,378 (79%) for metastatic diseases. Patients with benign
      tumors were younger, predominantly female, and were less likely to have
      preoperative comorbidities (all P < .037). Rates of major complications including
      infections, embolism, renal failure, stroke, coma, cardiac arrest, reoperation,
      and ventilator dependence were similar between the 2 groups (all P >= .05).
      Thirty-day mortality was .9% among patients with benign tumors and 1.4% among
      patients with metastases (P = .128). After adjusting for significant effects of
      age and major complications (both P <= .007), benign vs malignant diagnosis and
      extent of hepatectomy was not associated with 30-day survival (both P >= .083).
      CONCLUSIONS: Despite patients with benign disease being younger and healthier,
      risks of major complications are similar after hepatectomy for benign and
      metastatic disease. Hepatectomy should be offered selectively for patients with
      benign liver tumors.

PMID- 26307422
TI  - Lymph node size as a simple prognostic factor in node negative colon cancer and
      an alternative thesis to stage migration.
AB  - BACKGROUND: Stage migration is an accepted explanation for the association
      between lymph node (LN) yield and outcome in colon cancer. To investigate whether
      the alternative thesis of immune response is more likely, we performed a
      retrospective study. METHODS: We enrolled 239 cases of node negative cancers,
      which were categorized according to the number of LNs with diameters larger than
      5 mm (LN5) into the groups LN5-very low (0 to 1 LN5), LN5-low (2 to 5 LN5), and
      LN5-high (>=6 LN5). RESULTS: Significant differences were found in pT3/4 cancers
      with median survival times of 40, 57, and 71 months (P = .022) in the LN5-very
      low, LN5-low, and LN5-high groups, respectively. Multivariable analysis revealed
      that LN5 number and infiltration type were independent prognostic factors.
      CONCLUSIONS: LN size is prognostic in node negative colon cancer. The correct
      explanation for outcome differences associated with LN harvest is probably the
      activation status of LNs.

PMID- 26307423
TI  - Establishing the concurrent validity of general and technique-specific skills
      assessments in surgical education.
AB  - BACKGROUND: Laparoscopic surgery entails a unique skill set, but it is unclear
      whether it requires a specific assessment form or whether more general assessment
      tools can be applied. The purpose of this study was to assess the concurrent
      validity of 2 previously validated assessment scales. One scale designed
      specifically to assess laparoscopic skills and the other to assess more general
      surgical skills. METHODS: Postgraduate year 1-6 general surgery and urology
      residents (n = 33) performed a live laparoscopic cholecystectomy. Three surgeon
      raters scored their performance using previously validated objective structured
      assessment of technical skills (OSATS) and global operative assessment of
      laparoscopic skills rating scales. RESULTS: Pearson's correlation coefficient
      between global operative assessment of laparoscopic skills and OSATS rating
      scales was .975 (P = .01). CONCLUSIONS: The near total correlation between the 2
      scales questions the need for separate laparoscopic assessment tools,
      highlighting the real strengths of OSATS, the use of which allows for more
      consistent nomenclature and standardized skills assessment across surgical
      platforms.

PMID- 26307425
TI  - Phenol-substituted tetrapyrazinoporphyrazines: pH-dependent fluorescence in basic
      media.
AB  - Tetrapyrazinoporphyrazines (TPyzPzs) bearing one, two, four or eight 3,5-di(tert
      butyl)-4-hydroxyphenol moieties were synthesized as zinc(II) complexes and metal
      free derivatives. The deprotonation of the phenol using tetrabutylammonium
      hydroxide induced the formation of a strong donor for intramolecular charge
      transfer that switched OFF the red fluorescence (lambdaF ~660 nm) of the parent
      zinc TPyzPzs. The changes were fully reversible for TPyzPzs with one to four
      phenolic moieties, and an irreversible modification was observed for TPyzPzs
      substituted with eight phenols. The sensors were anchored to lipophilic particles
      in water, and a pKa approximately 12.5-12.7 was determined for the phenolic
      hydroxyl based on fluorescence changes in different buffers. In addition, a novel
      concept for fluorescence OFF-ON-OFF switching in metal-free TPyzPzs bearing
      phenolic moieties upon addition of specific amounts of base was demonstrated. 

PMID- 26307424
TI  - Incidence, risk factors, and management options for portal vein thrombosis after
      hepatectomy: a 14-year, single-center experience.
AB  - BACKGROUND: Portal vein thrombosis (PVT) after hepatectomy is rare; however, it
      increases mortality and morbidity. Few studies have been conducted that focused
      on PVT following major hepatectomy. METHODS: Patients who underwent hepatectomy
      at a single institution were retrospectively reviewed, and risk factors and
      management options were evaluated. RESULTS: Of the 1,193 patients undergoing
      hepatectomy, 25 patients developed PVT. Right-sided hepatectomy, caudate
      lobectomy, splenectomy, and postoperative bile leakage were independent risk
      factors for PVT following hepatectomy. PVT occurred more frequently after major
      hepatectomy compared with minor hepatectomy. Increased instability and reduced
      portal venous flow caused by kinking was the reason for increasing the risk of
      PVT after right-sided hepatectomy with caudate lobectomy. The new operative
      procedure, suturing the posterior wall of the portal vein with the anterior wall
      of the inferior vena cava, was effective for reducing the risk of PVT following
      right-sided hepatectomy. Operative thrombectomy showed significant benefits for
      PVT detected within 5 days after hepatectomy. CONCLUSIONS: PVT frequently occurs
      following major hepatectomy. Urgent operative thrombectomy is strongly
      recommended for PVT with early detection.

PMID- 26307426
TI  - Early and late adjustments of the photosynthetic traits and stomatal density in
      Quercus ilex L. grown in an ozone-enriched environment.
AB  - Quercus ilex L. seedlings were exposed in open-top chambers for one growing
      season to three levels of ozone (O3 ): charcoal filtered air, non-filtered air
      supplemented with +30% or +74% ambient air O3 . Key functional parameters related
      to photosynthetic performance and stomatal density were measured to evaluate the
      response mechanisms of Q. ilex to chronic O3 exposure, clarifying how
      ecophysiological traits are modulated during the season in an ozone-enriched
      environment. Dark respiration showed an early response to O3 exposure, increasing
      approximately 45% relative to charcoal-filtered air in both O3 enriched
      treatments. However, at the end of the growing season, maximum rate of
      assimilation (Amax ) and stomatal conductance (gs ) showed a decline (-13% and 
      36%, for Amax and gs , respectively) only in plants under higher O3 levels.
      Photosystem I functionality supported the capacity of Q. ilex to cope with
      oxidative stress by adjusting the energy flow partitioning inside the
      photosystems. The response to O3 was also characterised by increased stomatal
      density in both O3 enriched treatments relative to controls. Our results suggest
      that in order to improve the reliability of metrics for O3 risk assessment, the
      seasonal changes in the response of gs and photosynthetic machinery to O3 stress
      should be considered.

PMID- 26307428
TI  - Successful treatment of forehead lipoma depends on knowledge of the surgical
      anatomy: a step-by-step guide.
AB  - We review the anatomy of the frontal scalp in relation to the clinical features
      and surgical management of frontalis-associated lipoma. Awareness of this entity,
      coupled with sound regional anatomical knowledge, is essential to achieve good
      outcomes. 

PMID- 26307427
TI  - Essential components of early intervention programs for psychosis: Available
      intervention services in the United States.
AB  - Programs providing interventions for early psychosis are becoming commonplace in
      the United States (U.S.); however, the characteristics of existing services
      remain undocumented. We examined program characteristics, clinical services, and
      program eligibility criteria for outpatient early intervention programs across
      the U.S. using a semi-structured telephone interview. Content analysis was used
      to identify the presence or absence of program components, based in part on a
      recent list of essential evidence-based components recommended for early
      intervention programs (Addington, MacKenzie, Norman, Wang and Bond, 2013) as well
      as program characteristics, including eligibility criteria. A total of 34
      eligible programs were identified; 31 (91.2%) program representatives agreed to
      be interviewed. Of the examined components, the most prevalent were individual
      psychoeducation and outcomes tracking; the least prevalent were outreach services
      and communication with inpatient units. The populations served by US programs
      were most frequently defined by restrictions on the duration of psychosis and
      age. This study provides critical feedback on services for the early psychosis
      population and identifies research to practice gaps and areas for future
      improvement. 

PMID- 26307429
TI  - Novel TIA biomarkers identified by mass spectrometry-based proteomics.
AB  - BACKGROUND: Transient ischemic attacks remain a clinical diagnosis with
      significant variability between physicians. Finding reliable biomarkers to
      identify transient ischemic attacks would improve patient care and optimize
      treatment. AIM: Our aim is to identify novel serum TIA biomarkers through the use
      of mass spectroscopy-based proteomics. METHODS: Patients with transient
      neurologic symptoms were prospectively enrolled. Mass spectrometry-based
      proteomics, an unbiased method to identify candidate proteins, was used to test
      the serum of the patients for biomarkers of cerebral ischemia. Three candidate
      proteins were found, and serum concentrations of these proteins were measured by
      enzyme-linked immunosorbent assay in a second cohort of prospectively enrolled
      patients. The Student's t-test was used for comparison. The Benjamini-Hochberg
      false discovery rate controlling procedure for multiple comparison adjustments
      determined significance for the proteomic screen. RESULTS: Patients with
      transient ischemic attacks (n = 20), minor strokes (n = 15), and controls (i.e.
      migraine, seizure, n = 12) were enrolled in the first cohort. Ceruloplasmin,
      complement component C8 gamma (C8gamma), and platelet basic protein were
      significantly different between the ischemic group (transient ischemic attack and
      minor stroke) and the controls (P = 0.0001, P = 0.00027, P = 0.00105,
      respectively). A second cohort of patients with transient ischemic attack (n =
      22), minor stroke (n = 20), and controls' (n = 12) serum was enrolled. Platelet
      basic protein serum concentrations were increased in the ischemic samples
      compared with control (for transient ischemic attack alone, P = 0.019, for the
      ischemic group, P = 0.046). Ceruloplasmin trended towards increased
      concentrations in the ischemic group (P = 0.127); no significant difference in
      C8gamma (P = 0.44) was found. CONCLUSIONS: Utilizing mass spectrometry-based
      proteomics, platelet basic protein has been identified as a candidate serum
      biomarker for transient ischemic attack. This unbiased proteomic approach may be
      a promising method to identify novel biomarkers to more precisely diagnose
      transient ischemic attacks.

PMID- 26307431
TI  - Age at stroke onset influences the clinical outcome and health-related quality of
      life in pediatric ischemic stroke survivors.
AB  - AIM: Stroke in children occurs across different phases of brain development. Age
      at onset may affect outcome and health-related quality of life (HRQL). We
      evaluated the influence of age at stroke onset on the long-term neurological
      outcomes and HRQL of pediatric stroke survivors. METHOD: Children with ischemic
      stroke were recruited into three groups according to their age at onset of stroke
      (presumed perinatal, neonatal, and childhood). Neurological outcomes were
      assessed using the Pediatric Stroke Recovery and Recurrence Questionnaire. HRQL
      was evaluated using proxy report versions (2-18y) of the Pediatric Quality of
      Life Inventory (PedsQL 4.0). A chi(2) /Fisher's exact test and multivariable
      logistic regression analysis was performed for the neurological outcomes. HRQL
      scores from the different age groups were compared using linear regression.
      RESULTS: Ninety participants (presumed perinatal stroke, n=31; neonatal stroke,
      n=36; childhood stroke, n=23) were enrolled. Median age at the onset of stroke
      was 0.5 days and 3.7 years in neonatal and childhood participants respectively.
      Of the three groups, participants with presumed perinatal stroke demonstrated the
      worst global (p<0.002) and motor (p<0.001) outcomes and the lowest level of
      independence in daily activities (p<0.001). Parents reported the best global
      outcome and overall HRQL (p=0.007) after neonatal stroke. INTERPRETATION: The age
      at stroke onset has important implications regarding long-term clinical outcomes
      and HRQL for survivors. Individuals with presumed perinatal stroke should be
      considered at high-risk for poor outcomes.

PMID- 26307430
TI  - Clinical Research Office of the Endourological Society Global GreenLight Laser
      Study: Outcomes from a contemporary series of 713 patients.
AB  - OBJECTIVE: To evaluate the outcome in patients undergoing photoselective
      vaporization of the prostate for benign prostatic obstruction as part of the
      Clinical Research Office of the Endourological Society Global GreenLight Laser
      Study. METHODS: Data were collected on 713 patients with lower urinary tract
      symptoms suggestive of benign prostatic obstruction undergoing photoselective
      vaporization of the prostate at 25 centers worldwide, between April 2010 and
      April 2012. Three types of GreenLight laser powers were used: 80 W, 120 W or 180
      W. Intraoperative and postoperative complications were recorded. Outcome
      parameters measured at baseline, 6-12 weeks, 6 months and 12 months were: uroflow
      measurements, International Prostate Symptom Score; prostate-specific antigen and
      International Index of Erectile Function. RESULTS: Operating time was shortest
      with the 180-W laser at 53.8 min. Intraoperatively, bleeding occurred in 3.1% of
      patients. Statistically significant changes were reported in maximum flow rate,
      postvoid residual urine, International Prostate Symptom Score, quality of life
      score and prostate-specific antigen (P < 0.01) at each time-point assessed for
      the 80- and 120-W lasers as well as for the 180-W laser, with the exception of
      prostate-specific antigen at 6 months and 12 months. There were 14 Clavien-Dindo
      grade III-A complications and two grade III-B. The incontinence rate at 12 months
      was 6.3%, 4.5%, and 2.6% for the 80, 120 and 180 W lasers, respectively. The
      overall blood transfusion rate was 0.4%. CONCLUSIONS: Objective and subjective
      improvement after GreenLight laser treatment worldwide was significant at 1-year
      follow up. Morbidity and complications were low. Although not a randomized
      control study, the data can provide an indication of the outcome of the different
      GreenLight laser powers.

PMID- 26307432
TI  - The C-C chemokine receptor 6 (CCR6) is crucial for Th2-driven allergic
      conjunctivitis.
AB  - Allergic conjunctivitis from an allergen-driven Th2 response is characterized by
      conjunctival eosinophilic infiltration. Although CCL20-CCR6 axis has been
      reported to play a proinflammatory role in several murine models of autoimmune
      diseases including allergic diseases, their underlying mechanism needs to be
      investigated. We here examined whether CCL20-CCR6 axis could play a role in the
      development of allergic conjunctival inflammation using murine experimental
      allergic conjunctivitis (EAC) model induced by ovalbumin (OVA) allergen. Mice
      were challenged with consecutive 10days of OVA via conjunctival sac after
      systemic challenge with OVA and cholera toxin in alum. Several indicators for
      allergy were comparatively evaluated in wild-type and CCR6 KO EAC mice. Wild-type
      mice challenged with OVA via conjunctival sac following systemic challenge with
      OVA in alum had severe allergic conjunctivitis. The absence of CCR6 suppressed
      IgE secretion and allergic conjunctival inflammation. Reduced allergic
      inflammation was ascribable to reduced cytokine responses from Th-2 type in
      draining lymph node although Th17, regulatory T cells and dendritic cell subsets
      are not affected by the absence of CCR6. In addition, neutralization of CCR6
      ligand, CCL20 could repress allergic conjunctival inflammation. Our findings
      suggested that CCR6 might be crucial for optimal development of Th2 immune
      responses and further allergic conjunctival inflammation in EAC model. 

PMID- 26307433
TI  - Potentiation of cytokine-induced proliferation of human Natural Killer cells by
      intravenous immunoglobulin G.
AB  - Intravenous IgG (IVIG) therapy can be used for immunomodulation. IL-2 is an
      immunoregulatory cytokine. We evaluated IVIG modulation of human blood lymphocyte
      response to IL-2 and other cytokines. Neither IVIG nor low concentrations of IL-2
      (3-30U/ml) induced lymphocyte proliferation, but in combination they
      synergistically enhanced proliferation of NK cells. The CD56(bright) cells
      expanded more than CD56(dim) NK cells, with 90% of NK cells dividing up to 8
      generations by day 6, while <8% of T cells divided. IVIG also potentiated NK cell
      proliferation with IL-12, IL-15 and IL-18. The IVIG+cytokine-expanded NK cells
      were less cytotoxic for K562 cells, than NK cells with cytokine alone. IVIG also
      enhanced interferon-gamma production with IL-2, IL-12 and IL-18. In conclusion,
      IVIG selectively potentiates NK cell proliferation and interferon-gamma secretion
      with IL-2, IL-12, IL-15 and IL-18 in vitro. These findings warrant evaluation in
      vivo in relation to NK cells and the immunoregulatory actions of IVIG. 

PMID- 26307434
TI  - B cells from nuclear factor kB essential modulator deficient patients fail to
      differentiate to antibody secreting cells in response to TLR9 ligand.
AB  - Hypohidrotic ectodermal dysplasia (HED) consists of disorders resulting from
      molecular alterations of ectodysplasin-A (EDA) pathway. Hypomorphic mutations in
      NF-kB essential modulator, downstream EDA, result in HED with immunodeficiency
      (HED-ID), characterized by susceptibility to encapsulated pyogenic bacteria
      infections. Increased susceptibility to pneumococcal infections and poor response
      to polysaccharide antigens are associated with defect in T-independent B-cell
      immunity. We investigated B-cell differentiation and immunoglobulin secretion
      induced by the TLR9 ligand CpG in two HED-ID and in a HED patient caused by EDA
      mutations (XLHED). In HED-ID, only few B cells differentiated into plasma cells
      upon TLR9 stimulation and memory B cells did not produce IgG and IgA, but small
      amounts of IgM. Unexpectedly, memory B cells from XLHED patient failed to produce
      normal IgA or IgG amount upon TLR9 stimulation. Our findings expand the knowledge
      about the pathogenesis of humoral alterations in HED patients and help explain
      the susceptibility to pneumococcal infections. 

PMID- 26307435
TI  - Dose-response association of moderate-to-vigorous physical activity with
      cardiovascular biomarkers and all-cause mortality: Considerations by individual
      sports, exercise and recreational physical activities.
AB  - BACKGROUND: Previous research demonstrates that moderate-to-vigorous physical
      activity (MVPA) is associated with reduced all-cause mortality risk. Our
      understanding of whether individual physical activities are associated with all
      cause mortality is less understood. METHODS: Data from the 1999-2006 NHANES were
      employed, with follow-up through 2011. 48 different individual physical
      activities (e.g., swimming, running, bicycling) were assessed, and total MVPA MET
      min-month was calculated based on their responses to these 48 individual physical
      activities. RESULTS: Greater engagement in MVPA was associated with more
      favorable cardiovascular biomarkers, particularly for men. Even after adjustment
      for total MVPA, different individual physical activities were associated with
      cardiovascular biomarkers across gender. When compared to those not meeting
      guidelines (0-1999 MVPA MET-min-month), a dose-response association between MVPA
      and mortality was observed, with those engaging in 5 times the guideline level
      having the lowest risk of all-cause mortality (45% reduced risk). There was no
      evidence of a harmful effect of very high MVPA (e.g., 20,000+ MVPA MET-min
      month). CONCLUSIONS: Engaging in MVPA even below the minimum recommendation was
      associated with survival benefits, and the greatest survival effects occurred at
      a dose of approximately 5 times the minimum recommendation. Although very high
      levels (e.g., 10 times the minimum recommendation) of self-reported MVPA did not
      demonstrate the greatest survival effects, high levels of physical activity did
      not appear to have harmful effects.

PMID- 26307437
TI  - A sustainable system of systems approach: a new HFE paradigm.
AB  - Sustainability issues such as natural resource depletion, pollution and poor
      working conditions have no geographical boundaries in our interconnected world.
      To address these issues requires a paradigm shift within human factors and
      ergonomics (HFE), to think beyond a bounded, linear model understanding towards a
      broader systems framework. For this reason, we introduce a sustainable system of
      systems model that integrates the current hierarchical conceptualisation of
      possible interventions (i.e., micro-, meso- and macro-ergonomics) with important
      concepts from the sustainability literature, including the triple bottom line
      approach and the notion of time frames. Two practical examples from the HFE
      literature are presented to illustrate the model. The implications of this
      paradigm shift for HFE researchers and practitioners are discussed and include
      the long-term sustainability of the HFE community and comprehensive solutions to
      problems that consider the emergent issues that arise from this interconnected
      world. PRACTITIONER SUMMARY: A sustainable world requires a broader systems
      thinking than that which currently exists in ergonomics. This study proposes a
      sustainable system of systems model that incorporates ideas from the ecological
      sciences, notably a nested hierarchy of systems and a hierarchical time
      dimension. The implications for sustainable design and the sustainability of the
      HFE community are considered.

PMID- 26307436
TI  - Strain-specific induction of endometrial periglandular fibrosis in mice exposed
      during adulthood to the endocrine disrupting chemical bisphenol A.
AB  - The aim of this study was to compare effects of bisphenol A (BPA) on collagen
      accumulation in uteri of two mouse strains. Adult C57Bl/6N and CD-1 mice were
      exposed to dietary BPA (0.004-40mg/kg/day) or 17alpha-ethinyl estradiol (0.00002
      0.001mg/kg/day) as effect control. An equine endometrosis-like phenotype with
      increased gland nesting and periglandular collagen accumulation was
      characteristic of unexposed C57Bl/6N, but not CD-1, endometrium. BPA non
      monotonically increased gland nest density and periglandular collagen
      accumulation in both strains. Increased collagen I and III expression, decreased
      matrix metalloproteinase 2 (MMP2) and MMP14 expression, and increased immune
      response were associated with the endometrosis phenotype in the C57Bl/6N strain
      and the 30ppm BPA CD-1 group. The association between the pro-collagen shift in
      increased collagen expression and decreased MMP2 expression and activity implies
      that strain differences and BPA exposure alter regulation of endometrial
      remodeling and contribute to increased fibrosis, a component of several human
      uterine diseases. 

PMID- 26307438
TI  - Printed dose-recording tag based on organic complementary circuits and
      ferroelectric nonvolatile memories.
AB  - We have demonstrated a printed electronic tag that monitors time-integrated
      sensor signals and writes to nonvolatile memories for later readout. The tag is
      additively fabricated on flexible plastic foil and comprises a thermistor
      divider, complementary organic circuits, and two nonvolatile memory cells. With a
      supply voltage below 30 V, the threshold temperatures can be tuned between 0 
      degrees C and 80  degrees C. The time-temperature dose measurement is calibrated
      for minute-scale integration. The two memory bits are sequentially written in a
      thermometer code to provide an accumulated dose record. 

PMID- 26307439
TI  - Professional Hubris and its Consequences: Why Organizations of Health-Care
      Professions Should Not Adopt Ethically Controversial Positions.
AB  - In this article, I argue that professional healthcare organizations such as the
      AMA and ANA ought not to take controversial stances on professional ethics. I
      address the best putative arguments in favor of taking such stances, and argue
      that none are convincing. I then argue that the sort of stance-taking at issue
      has pernicious consequences: it stands to curb critical thought in social,
      political, and legal debates, increase moral distress among clinicians, and
      alienate clinicians from their professional societies. Thus, because there are no
      good arguments in favor of stance-taking and at least some risks in doing so,
      professional organizations should refrain from adopting the sort of ethically
      controversial positions at issue. 

PMID- 26307440
TI  - Stomatal Blue Light Response Is Present in Early Vascular Plants.
AB  - Light is a major environmental factor required for stomatal opening. Blue light
      (BL) induces stomatal opening in higher plants as a signal under the
      photosynthetic active radiation. The stomatal BL response is not present in the
      fern species of Polypodiopsida. The acquisition of a stomatal BL response might
      provide competitive advantages in both the uptake of CO2 and prevention of water
      loss with the ability to rapidly open and close stomata. We surveyed the stomatal
      opening in response to strong red light (RL) and weak BL under the RL with gas
      exchange technique in a diverse selection of plant species from euphyllophytes,
      including spermatophytes and monilophytes, to lycophytes. We showed the presence
      of RL-induced stomatal opening in most of these species and found that the BL
      responses operated in all euphyllophytes except Polypodiopsida. We also confirmed
      that the stomatal opening in lycophytes, the early vascular plants, is driven by
      plasma membrane proton-translocating adenosine triphosphatase and K(+)
      accumulation in guard cells, which is the same mechanism operating in stomata of
      angiosperms. These results suggest that the early vascular plants respond to both
      RL and BL and actively regulate stomatal aperture. We also found three plant
      species that absolutely require BL for both stomatal opening and photosynthetic
      CO2 fixation, including a gymnosperm, C. revoluta, and the ferns Equisetum
      hyemale and Psilotum nudum. 

PMID- 26307441
TI  - Disinfection by hydrogen peroxide nebulization increases susceptibility to avian
      pathogenic Escherichia coli.
AB  - BACKGROUND: Avian pathogenic Escherichia coli (APEC) are the major cause of
      economic losses in the poultry industry worldwide. Traditionally, antibiotics are
      used to treat and prevent colibacillosis in broilers. Due to resistance
      development other ways of preventing/treating the disease have to be found.
      Therefore during this study the nebulization of low concentrations of hydrogen
      peroxide (H2O2) was tested in the presence of chickens to lower pathogenicity of
      APEC. RESULTS: Significantly higher total lesion scores and higher E. coli
      concentrations were found in the spleen of chickens exposed to 2% H2O2 compared
      to those exposed to 1% H2O2 and control chickens which had been exposed to
      nebulization with distilled water. Higher total lesions scores and E. coli
      concentrations in the spleen were found in chickens exposed to 1% H2O2 in
      comparison to control chickens (not significant). CONCLUSION: H2O2 is rendering
      animals more prone to APEC infection contraindicating H2O2 nebulization in the
      presence of chickens.

PMID- 26307442
TI  - The influence of ecological and geographical context in the radiation of
      Neotropical sigmodontine rodents.
AB  - BACKGROUND: Much debate has focused on how transitions in life history have
      influenced the proliferation of some clades. Rodents of the subfamily
      Sigmodontinae (family Cricetidae) comprise one of the most diverse clades of
      Neotropical mammals (~400 living species in 86 genera). These rodents occupy a
      wide range of habitats and lifestyles so that ecological context seems relevant
      to understand the evolution of this group. Several changes in the landscape of
      South America through the Neogene might have provided vast resources and
      opportunity to diversify. The aim of this study was to examine whether
      transitions between i) lowland and montane habitats, ii) open vegetation and
      forest, and iii) distinct molar architectures are correlated with shifts in
      diversification rates and to characterize the general pattern of diversification.
      RESULTS: Based on a dense taxon sampling of 269 species, we recovered a new
      phylogeny of Sigmodontinae that is topologically consistent with those of
      previous studies. It indicates that the subfamily and its major lineages appeared
      during the Late Miocene. Analyses suggest that vegetation type and elevational
      range are correlated with diversification rates, but not molar architecture.
      Tropical lowlands accumulated more lineage diversity than other areas and also
      supported high speciation rates. Across the radiation the subfamily Sigmodontinae
      appear to have experienced a decline in diversification rate through time. We
      detected mixed evidence for lineage-specific diversification rate shifts (e.g.,
      leading to the clades of Akodon, Bibimys, Calomys and Thomasomys). CONCLUSION: We
      report that the evolution of habitat preference (considering vegetation type and
      elevational range) was associated with diversification rates among sigmodontine
      rodents. We propose that the observed diversification slowdown might be the
      result of ecological or geographical constraints. Our results also highlight the
      influence of the tropical lowlands -which might have acted as both "a cradle and
      a museum of species." The tropical lowlands accumulated greater diversity than
      the remainder of the group's range.

PMID- 26307443
TI  - Cloning a neutral protease of Clostridium histolyticum, determining its substrate
      specificity, and designing a specific substrate.
AB  - Islet transplantation is a prospective treatment for restoring normoglycemia in
      patients with type 1 diabetes. Islet isolation from pancreases by decomposition
      with proteolytic enzymes is necessary for transplantation. Two collagenases,
      collagenase class I (ColG) and collagenase class II (ColH), from Clostridium
      histolyticum have been used for islet isolation. Neutral proteases have been
      added to the collagenases for human islet isolation. A neutral protease from C.
      histolyticum (NP) and thermolysin from Bacillus thermoproteolyicus has been used
      for the purpose. Thermolysin is an extensively studied enzyme, but NP is not well
      known. We therefore cloned the gene encoding NP and constructed a Bacillus
      subtilis overexpression strain. The expressed enzyme was purified, and its
      substrate specificity was examined. We observed that the substrate specificity of
      NP was higher than that of thermolysin, and that the protein digestion activities
      of NP, as determined by colorimetric methods, were lower than those of
      thermolysin. It seems that decomposition using NP does not negatively affect
      islets during islet preparation from pancreases. Furthermore, we designed a novel
      substrate that allows the measurement of NP activity specifically in the enzyme
      mixture for islet preparation and the culture broth of C. histolyticum. The
      activity of NP can also be monitored during islet isolation. We hope the purified
      enzyme and this specific substrate contribute to the optimization of islet
      isolation from pancreases and that it leads to the success of islet
      transplantation and the improvement of the quality of life (QOL) for diabetic
      patients. 

PMID- 26307444
TI  - Short antimicrobial peptides as cosmetic ingredients to deter dermatological
      pathogens.
AB  - Antimicrobial peptides (AMPs) are components of the innate immune system in many
      species of animals. Their diverse spectrum of activity against microbial
      pathogens, both as innate defense molecules and immunomodulators, makes them
      attractive candidates for the development of a new generation of antibiotics.
      Although the potential immunogenicity of AMPs means they are not suitable for
      injection and their susceptibility to digestive peptidases is likely to reduce
      their oral efficacy, they are ideal for topical formulations such as lotions,
      creams, shampoos, and wound dressings and could therefore be valuable products
      for the cosmetic industry. In this context, short AMPs (<20 amino acids) lacking
      disulfide bonds combine optimal antimicrobial activity with inexpensive chemical
      synthesis and are therefore more compatible with large-scale production and the
      modifications required to ensure stability, low toxicity, and microbial
      specificity. Proof-of-concept for the application of AMPs as novel anti
      infectives has already been provided in clinical trials. This perspective
      considers the anti-infective properties of short AMPs lacking disulfide bonds,
      which are active against dermatologically important microflora. We consider the
      challenges that need to be addressed to facilitate the prophylactic application
      of AMPs in personal care products. 

PMID- 26307445
TI  - Multiple loss-of-function variants of taste receptors in modern humans.
AB  - Despite recent advances in the knowledge of interindividual taste differences,
      the underlying genetic backgrounds have remained to be fully elucidated. Much of
      the taste variation among different mammalian species can be explained by
      pseudogenization of taste receptors. Here I investigated whether the most recent
      disruptions of taste receptor genes segregate with their intact forms in modern
      humans by analyzing 14 ethnically diverse populations. The results revealed an
      unprecedented prevalence of 25 segregating loss-of-function (LoF) taste receptor
      variants, identifying one of the most pronounced cases of functional population
      diversity in the human genome. LoF variant frequency in taste receptors (2.10%)
      was considerably higher than the overall LoF frequency in human genome (0.16%).
      In particular, molecular evolutionary rates of candidate sour (14.7%) and bitter
      (1.8%) receptors were far higher in humans than those of sweet (0.02%), salty
      (0.05%), and umami (0.17%) receptors compared with other carnivorous mammals,
      although not all of the taste receptors were identified. Many LoF variants are
      population-specific, some of which arose even after population differentiation,
      not before divergence of the modern and archaic human. I conclude that modern
      humans might have been losing some sour and bitter receptor genes because of high
      frequency LoF variants. 

PMID- 26307447
TI  - Incidence and spectrum of paraneoplastic neurological syndromes: single center
      study.
AB  - Paraneoplastic neurological syndromes (PNS) are remote effects of cancer. They
      are much less common, but are nevertheless important because they cause severe
      neurological morbidity and mortality. The present cases were studied to
      characterize the clinical features of patients of suspected PNS and to study
      their association with different types of tumors. In this study conducted from a
      super speciality teaching institute from South India, forty five (incidence
      0.25%) patients were diagnosed with PNS based on the clinical data. They were
      subdivided into two groups patients with central nervous system (CNS)
      manifestations and those with neuromuscular manifestations. Immunological markers
      were assessed in a subset of patients. Majority of them (75.6%) were above 40
      years. There was no sex predilection and a chronic presentation was common
      (42.2%). While more than half had involvement of peripheral nervous system
      (64.4%), CNS manifestations were present in 16 (35.6%) cases. Immunological
      markers were present in 10 out of 14 (58.8%) patients. Classic PNS was seen 22
      cases (48.9%), while 23 (51.1%) were non classical. Most common tumor was lung
      cancer followed by myeloma and breast carcinoma. Present study construed that, in
      patients with neurological syndromes of unknown cause, search should be focused
      for occult malignancy based on the phenotype and onconeural antibodies, targeting
      the lung and breast in particular.

PMID- 26307446
TI  - Long-term risk of radionecrosis and imaging changes after stereotactic
      radiosurgery for brain metastases.
AB  - Radionecrosis is a well-characterized effect of stereotactic radiosurgery (SRS)
      and is occasionally associated with serious neurologic sequelae. Here, we
      investigated the incidence of and clinical variables associated with the
      development of radionecrosis and related radiographic changes after SRS for brain
      metastases in a cohort of patients with long-term follow up. 271 brain metastases
      treated with single-fraction linear accelerator-based SRS were analyzed.
      Radionecrosis was diagnosed either pathologically or radiographically. Univariate
      and multivariate Cox regression was performed to determine the association
      between radionecrosis and clinical factors available prior to treatment planning.
      After median follow up of 17.2 months, radionecrosis was observed in 70 (25.8%)
      lesions, including 47 (17.3%) symptomatic cases. 22 of 70 cases (31.4%) were
      diagnosed pathologically and 48 (68.6%) were diagnosed radiographically. The
      actuarial incidence of radionecrosis was 5.2% at 6 months, 17.2% at 12 months and
      34.0% at 24 months. On univariate analysis, radionecrosis was associated with
      maximum tumor diameter (HR 3.55, p < 0.001), prior whole brain radiotherapy (HR
      2.21, p = 0.004), prescription dose (HR 0.56, p = 0.02) and histology other than
      non-small cell lung, breast or melanoma (HR 1.85, p = 0.04). On multivariate
      analysis, only maximum tumor diameter (HR 3.10, p < 0.001) was associated with
      radionecrosis risk. This data demonstrates that with close imaging follow-up,
      radionecrosis after single-fraction SRS for brain metastases is not uncommon.
      Maximum tumor diameter on pre-treatment MR imaging can provide a reliable
      estimate of radionecrosis risk prior to treatment planning, with the greatest
      risk among tumors measuring >1 cm.

PMID- 26307448
TI  - Schisandrin B induces an Nrf2-mediated thioredoxin expression and suppresses the
      activation of inflammasome in vitro and in vivo.
AB  - Reactive oxygen species (ROS)-mediated activation of inflammasome is involved in
      the development of a wide spectrum of diseases. We aimed to investigate whether (
      )schisandrin B [(-)Sch B], a phytochemical that can induce cellular antioxidant
      response, can suppress the inflammasome activation. Results showed that (-)Sch B
      can induce an nuclear factor erythroid 2-related factor 2-driven thioredoxin
      expression in primary peritoneal macrophages and cultured RAW264.7 macrophages. A
      4-h priming of peritoneal macrophages with LPS followed by a 30-min incubation
      with ATP caused the activation of caspase 1 and the release of IL-1beta,
      indicative of inflammasome activation. Although LPS/ATP did not activate
      inflammasome in RAW264.7 macrophages, it caused the ROS-dependent c-Jun N
      terminal kinase1/2 (JNK1/2) activation and an associated lactate dehydrogenase
      (LDH) release in RAW264.7 macrophages, an indication of cytotoxicity. (-)Sch B
      suppressed the LPS/ATP-induced activation of caspase 1 and release of IL-1beta in
      peritoneal macrophages. (-)Sch B also attenuated the LPS/ATP-induced ROS
      production, JNK1/2 activation and LDH release in RAW264.7 macrophages. The
      ability of (-)Sch B to suppress LPS/ATP-mediated inflammation in vitro was
      further confirmed by an animal study, in which schisandrin B treatment (2 mmol/kg
      p.o.) ameliorated the Imject Alum-induced peritonitis, as indicated by
      suppressions of caspase1 activation and plasma IL-1beta level. The ensemble of
      results suggests that (-)Sch B may offer a promising prospect for preventing the
      inflammasome-mediated disorders.

PMID- 26307449
TI  - Highly abundant defense proteins in human sweat as revealed by targeted
      proteomics and label-free quantification mass spectrometry.
AB  - BACKGROUND: The healthy human skin with its effective antimicrobial defense
      system forms an efficient barrier against invading pathogens. There is evidence
      suggesting that the composition of this chemical barrier varies between diseases,
      making the easily collected sweat an ideal candidate for biomarker discoveries.
      OBJECTIVE: Our aim was to provide information about the normal composition of the
      sweat, and to study the chemical barrier found at the surface of skin. METHODS:
      Sweat samples from healthy individuals were collected during sauna bathing, and
      the global protein panel was analysed by label-free mass spectrometry. SRM-based
      targeted proteomic methods were designed and stable isotope labelled reference
      peptides were used for method validation. RESULTS: Ninety-five sweat proteins
      were identified, 20 of them were novel proteins. It was shown that dermcidin is
      the most abundant sweat protein, and along with apolipoprotein D, clusterin,
      prolactin-inducible protein and serum albumin, they make up 91% of secreted sweat
      proteins. The roles of these highly abundant proteins were reviewed; all of which
      have protective functions, highlighting the importance of sweat glands in
      composing the first line of innate immune defense system, and maintaining the
      epidermal barrier integrity. CONCLUSION: Our findings with regard to the proteins
      forming the chemical barrier of the skin as determined by label-free
      quantification and targeted proteomics methods are in accordance with previous
      studies, and can be further used as a starting point for non-invasive sweat
      biomarker research.

PMID- 26307450
TI  - Graded vertical rectus tenotomy for small-angle cyclovertical strabismus in
      sagging eye syndrome.
AB  - BACKGROUND/AIMS: Graded vertical rectus tenotomy (GVRT) is postulated as
      effective for small-angle vertical heterotropia. We aimed to determine the dosing
      recommendations for GVRT in sagging eye syndrome (SES). METHODS: This was a
      retrospective, observational study of surgical outcomes for GVRT from 2009 to
      2014 in a single surgeon's academic practice. There were 37 (20 women) patients
      of average age 68+/-10 (SD) years with comitant or incomitant hypertropia
      <=10Delta caused by SES. The main outcome measure was the dose-effect of GVRT
      required to correct intraoperative hypertropia. RESULTS: Preoperative average
      central gaze hypertropia measured 4.7+/-2.2Delta. Three patients underwent repeat
      GVRT for residual or consecutive hypertropia, one undergoing it twice. All
      surgeries were analysed, increasing the total operations to 41. The inferior
      rectus tendon in the hypotropic eye was operated in 32 eyes, and the superior
      rectus tendon in the hypertropic eye in 9 eyes. Mean tenotomy was 68+/-19% of
      tendon width. Hypertropia was always eliminated intraoperatively by progressive
      GVRT. Mean hypertropia was 1.1+/-1.6Delta at average 93 days postoperatively.
      Linear regression demonstrated that 3-6Delta hypertropia correction requires 30%
      90% graded tenotomy (R(2)=0.32, p<0.0001), but with substantial individual
      variability. Undercorrection necessitated reoperation in 10% of cases.
      CONCLUSION: GVRT precisely corrects hypertropia of up to 10Delta, but because of
      variable effect, it should be performed with intraoperative monitoring under
      topical anaesthesia.

PMID- 26307451
TI  - Optic neuropathy in late-onset neurodegenerative Chediak-Higashi syndrome.
AB  - BACKGROUND: The classic form of Chediak-Higashi syndrome (CHS), an autosomal
      recessive disorder of lysosomal trafficking with childhood onset caused by
      mutations in ITALIC! LYST, is typified ophthalmologically by ocular albinism with
      vision loss attributed to foveal hypoplasia or nystagmus. Optic nerve involvement
      and ophthalmological manifestations of the late-onset neurodegenerative form of
      CHS are rarely reported and poorly detailed. METHODS: Case series detailing
      ophthalmological and neurological findings in three adult siblings with the late
      onset form of CHS. RESULTS: All three affected siblings lacked features of ocular
      albinism and demonstrated significant optic nerve involvement as evidenced by
      loss of colour and contrast vision, central visual field loss, optic nerve
      pallor, retinal nerve fibre layer thinning by optical coherence tomography (OCT)
      and abnormal visual evoked potential, with severity corresponding linearly to age
      of the sibling and severity of neurological disease. Further, unusual prominence
      of a 'third line' on macular OCT that may be due to abnormal melanosomes was seen
      in all three siblings and in their father. Neurological involvement included
      parkinsonism, cerebellar ataxia and spastic paraparesis. CONCLUSIONS: This report
      expands the ophthalmological phenotype of the late-onset neurodegenerative form
      of CHS to include optic neuropathy with progressive vision loss, even in the
      absence of ocular albinism, and abnormal prominence of the interdigitation zone
      between cone outer segment tips and apical processes of retinal pigment
      epithelium cells on macular OCT.

PMID- 26307452
TI  - A novel automated segmentation method for retinal layers in OCT images proves
      retinal degeneration after optic neuritis.
AB  - AIM: The evaluation of inner retinal layer thickness can serve as a direct
      biomarker for monitoring the course of inflammatory diseases of the central
      nervous system such as multiple sclerosis (MS). Using optical coherence
      tomography (OCT), thinning of the retinal nerve fibre layer and changes in deeper
      retinal layers have been observed in patients with MS. Here, we first compare a
      novel method for automated segmentation of OCT images with manual segmentation
      using two cohorts of patients with MS. Using this method, we also aimed to
      reproduce previous findings showing retinal degeneration following optic neuritis
      (ON) in MS. METHODS: Based on a 5*5 expansion of the Prewitt operator to
      efficiently calculate the gradient of image intensity, we introduce an automated
      algorithm for the segmentation of intraretinal layers. We evaluated this
      algorithm by comparison to manually segmented two-dimensional OCT images at the
      macular level for 125 patients from two separate cohorts of patients with MS. Of
      these patients, 52 had suffered from unilateral ON+ within 6 months prior to
      measurement. RESULTS: When comparing ON+ eyes with ON- eyes, both manual and
      automated segmentation demonstrated a significant inter-eye thinning in the
      ganglion cell layer in ON+ eyes. We also observed an increased thickness of the
      inner nuclear (INL) and the outer segment-retinal pigment epithelium (OS-RPE)
      layers of ON+ eyes in both cohorts. These findings corroborate previous data,
      thus demonstrating the validity of our approach. CONCLUSIONS: The algorithm
      presented here was found to be a valid tool for replacing cumbersome manual
      segmentation methods in the quantification of inner retinal layers in OCT. The
      observed increases in thickness of INL and OS-RPE may be attributed to primary
      retinal inflammation, repair and/or plasticity mechanisms following the immune
      attack.

PMID- 26307453
TI  - The time dependent association of adrenaline administration and survival from out
      of-hospital cardiac arrest.
AB  - BACKGROUND: Recommended for decades, the therapeutic value of adrenaline
      (epinephrine) in the resuscitation of patients with out-of-hospital cardiac
      arrest (OHCA) is controversial. PURPOSE: To investigate the possible time
      dependent outcomes associated with adrenaline administration by Emergency Medical
      Services personnel (EMS). METHODS: A retrospective analysis of prospectively
      collected data from a near statewide cardiac resuscitation database between 1
      January 2005 and 30 November 2013. Multivariable logistic regression was used to
      analyze the effect of the time interval between EMS dispatch and the initial dose
      of adrenaline on survival. The primary endpoints were survival to hospital
      discharge and favourable neurologic outcome. RESULTS: Data from 3469 patients
      with witnessed OHCA were analyzed. Their mean age was 66.3 years and 69% were
      male. An initially shockable rhythm was present in 41.8% of patients. Based on a
      multivariable logistic regression model with initial adrenaline administration
      time interval (AATI) from EMS dispatch as the covariate, survival was greatest
      when adrenaline was administered very early but decreased rapidly with increasing
      (AATI); odds ratio 0.94 (95% Confidence Interval (CI) 0.92-0.97). The AATI had no
      significant effect on good neurological outcome (OR=0.96, 95% CI=0.90-1.02).
      CONCLUSIONS: In patients with OHCA, survival to hospital discharge was greater in
      those treated early with adrenaline by EMS especially in the subset of patients
      with a shockable rhythm. However survival rapidly decreased with increasing
      adrenaline administration time intervals (AATI).

PMID- 26307454
TI  - SCR96, a small cysteine-rich secretory protein of Phytophthora cactorum, can
      trigger cell death in the Solanaceae and is important for pathogenicity and
      oxidative stress tolerance.
AB  - Peptides and small molecules produced by both the plant pathogen Phytophthora and
      host plants in the apoplastic space mediate the relationship between the
      interplaying organisms. Various Phytophthora apoplastic effectors, including
      small cysteine-rich (SCR) secretory proteins, have been identified, but their
      roles during interaction remain to be determined. Here, we identified an SCR
      effector encoded by scr96, one of three novel genes encoding SCR proteins in P.
      cactorum with similarity to the P. cactorum phytotoxic protein PcF. Together with
      the other two genes, scr96 was transcriptionally induced throughout the
      developmental and infection stages of the pathogen. These genes triggered plant
      cell death (PCD) in the Solanaceae, including Nicotiana benthamiana and tomato.
      The scr96 gene did not show single nucleotide polymorphisms in a collection of P.
      cactorum isolates from different countries and host plants, suggesting that its
      role is essential and non-redundant during infection. Homologues of SCR96 were
      identified only in oomycetes, but not in fungi and other organisms. A stable
      protoplast transformation protocol was adapted for P. cactorum using green
      fluorescent protein as a marker. The silencing of scr96 in P. cactorum caused
      gene-silenced transformants to lose their pathogenicity on host plants and these
      transformants were significantly more sensitive to oxidative stress. Transient
      expression of scr96 partially recovered the virulence of gene-silenced
      transformants on plants. Overall, our results indicate that the P. cactorum scr96
      gene encodes an important virulence factor that not only causes PCD in host
      plants, but is also important for pathogenicity and oxidative stress tolerance. 

PMID- 26307456
TI  - A review of the functionalities of smart walkers.
AB  - There is a need to conceptualize and improve the investigation and developments
      in assistive devices, focusing on the design and effectiveness of walkers in the
      user's rehabilitation process and functional compensation. This review surveys
      the importance of smart walkers in maintaining mobility and discusses their
      potential in rehabilitation and their demands as assistive devices. It also
      presents related research in addressing and quantifying the smart walker's
      efficiency and influence on gait. Besides, it discusses smart walkers focusing on
      studies related to the concept of autonomous and shared-control and manual
      guidance, the use of smart walkers as personal helpers to sit-to-stand and
      diagnostic tools for patients' rehabilitation through the evaluation of their
      gait. 

PMID- 26307457
TI  - Effect of power-assisted hand-rim wheelchair propulsion on shoulder load in
      experienced wheelchair users: A pilot study with an instrumented wheelchair.
AB  - This study aims to compare hand-rim and power-assisted hand-rim propulsion on
      potential risk factors for shoulder overuse injuries: intensity and repetition of
      shoulder loading and force generation in the extremes of shoulder motion. Eleven
      experienced hand-rim wheelchair users propelled an instrumented wheelchair on a
      treadmill while upper-extremity kinematic, kinetic and surface
      electromyographical data was collected during propulsion with and without power
      assist. As a result during power-assisted propulsion the peak resultant force
      exerted at the hand-rim decreased and was performed with significantly less
      abduction and internal rotation at the shoulder. At shoulder level the anterior
      directed force and internal rotation and flexion moments decreased significantly.
      In addition, posterior and the minimal inferior directed forces and the external
      rotation moment significantly increased. The stroke angle decreased
      significantly, as did maximum shoulder flexion, extension, abduction and internal
      rotation. Stroke-frequency significantly increased. Muscle activation in the
      anterior deltoid and pectoralis major also decreased significantly. In
      conclusion, compared to hand-rim propulsion power-assisted propulsion seems
      effective in reducing potential risk factors of overuse injuries with the highest
      gain on decreased range of motion of the shoulder joint, lower peak propulsion
      force on the rim and reduced muscle activity. 

PMID- 26307458
TI  - Response of single cell with acute angle exposed to an external electric field.
AB  - It is known that the electric field incurs effects on the living cells.
      Predicting the response of single cell or multilayer cells to induced alternative
      or static eclectic field has permanently been a challenge. In the present study a
      first order single cell with acute angle under the influence of external electric
      field is considered. The cell division stage or the special condition of
      reshaping is modelled with a cone being connected. In the case of cell divisions,
      anaphase, it can be considered with two cones that connected nose-to-nose. Each
      cone consists of two regions. The first is the membrane modelled with a
      superficial layer, and the second is cytoplasm at the core. A Laplace equation is
      written for this model and the distribution of its electric field is a sharp
      point in the single cell for which an acute angle model is calculated. 

PMID- 26307455
TI  - Estrogen receptor beta in Alzheimer's disease: From mechanisms to therapeutics.
AB  - Alzheimer's disease (AD) disproportionally affects women and men. The female
      susceptibility for AD has been largely associated with the loss of ovarian sex
      hormones during menopause. This review examines the current understanding of the
      role of estrogen receptor beta (ERbeta) in the regulation of neurological health
      and its implication in the development and intervention of AD. Since its
      discovery in 1996, research conducted over the last 15-20 years has documented a
      great deal of evidence indicating that ERbeta plays a pivotal role in a broad
      spectrum of brain activities from development to aging. ERbeta genetic
      polymorphisms have been associated with cognitive impairment and increased risk
      for AD predominantly in women. The role of ERbeta in the intervention of AD has
      been demonstrated by the alteration of AD pathology in response to treatment with
      ERbeta-selective modulators in transgenic models that display pronounced plaque
      and tangle histopathological presentations as well as learning and memory
      deficits. Future studies that explore the potential interactions between ERbeta
      signaling and the genetic isoforms of human apolipoprotein E (APOE) in brain
      aging and development of AD-risk phenotype are critically needed. The current
      trend of lost-in-translation in AD drug development that has primarily been based
      on early-onset familial AD (FAD) models underscores the urgent need for novel
      models that recapitulate the etiology of late-onset sporadic AD (SAD), the most
      common form of AD representing more than 95% of the current human AD population.
      Combining the use of FAD-related models that generally have excellent face
      validity with SAD-related models that hold more reliable construct validity would
      together increase the predictive validity of preclinical findings for successful
      translation into humans.

PMID- 26307459
TI  - A principal component analysis is conducted for a case series quality appraisal
      checklist.
AB  - OBJECTIVE: Because of a lack of a control group, a case-series study is
      considered one of the weaker study designs from which to obtain evidence on
      treatment effectiveness. Under certain circumstances, however, this is the only
      available evidence to inform health-care decisions. This study's intent was to
      develop and validate a quality appraisal checklist specifically for case-series
      studies. STUDY DESIGN AND SETTING: A modified Delphi process was used to develop
      the checklist, which was then used by multiple researchers to appraise a random
      sample of 105 case-series studies. A principal component analysis of these
      appraisals was conducted to further refine the checklist. RESULTS: The modified
      Delphi process resulted in a 20-criterion checklist. The principal component
      analysis of the appraisals for the 105 case-series studies revealed two
      components. The first component (10 criteria) indicated the extent to which a
      case series presented traditional features of a statistical hypothesis-testing
      paradigm. The second component (seven criteria) indicated whether detailed
      descriptions of the subjects' characteristics that might feature in the
      experimental design were present, particularly in judgments about the likelihood
      of confounding. CONCLUSION: This quality appraisal checklist may be useful in
      assessing case-series studies, but further validation of the checklist is
      required.

PMID- 26307460
TI  - Identification of gene mutation in patients with osteogenesis imperfect using
      high resolution melting analysis.
AB  - Osteogenesis imperfecta (OI), a congenital bone disorder, is caused by mutations
      in COL1A1 and COL1A2 genes, leading to deficiency of type I collagen. The high
      resolution melting (HRM) analysis has been used for detecting mutations,
      polymorphisms and epigenetic alteration in double-stranded DNAs. This study was
      to evaluate the potential application of HRM analysis for identifying gene
      mutations in patients with OI. This study included four children with OI and
      their parents and fifty normal people as controls. Blood samples were collected
      for HRM analysis of PCR-amplified exons and flanking DNA sequences of COL1A1 and
      COL1A2 genes. Direct gene sequencing was performed to validate HRM-identified
      gene mutations. As compared to controls, HRM analysis of samples form children
      with OI showed abnormal melting curves in exons 11 and 33-34 of the COL1A1 gene
      and exons 19 and 48 of the COL1A2 gene, which indicates the presence of
      heterozygous mutations in COL1A1 and COL1A2 genes. In addition to two known
      mutations in the COL1A2 gene, c.982G > A and c.3197G > T, sequencing analysis
      identified two novel mutations in the COL1A1 gene, c.2321delC and c.768dupC
      mutations, which function as premature stop codons. These results support future
      studies of applying HRM analysis as a diagnostic approach for OI. 

PMID- 26307461
TI  - Double hysteresis loops and large negative and positive electrocaloric effects in
      tetragonal ferroelectrics.
AB  - Phase field modelling and thermodynamic analysis are employed to investigate
      depolarization and compression induced large negative and positive electrocaloric
      effects (ECEs) in ferroelectric tetragonal crystalline nanoparticles. The results
      show that double-hysteresis loops of polarization versus electric field dominate
      at temperatures below the Curie temperature of the ferroelectric material, when
      the mechanical compression exceeds a critical value. In addition to the mechanism
      of pseudo-first-order phase transition (PFOPT), the double-hysteresis loops are
      also caused by the abrupt rise of macroscopic polarization from the abc phase to
      the c phase or the sudden fall of macroscopic polarization from the c phase to
      the abc phase when the temperature increases. This phenomenon is called the
      electric-field-induced-pseudo-phase transition (EFIPPT) in the present study.
      Similar to the two types of PFOPTs, the two types of EFIPPTs cause large negative
      and positive ECEs, respectively, and give the maximum absolute values of negative
      and positive adiabatic temperature change (ATC DeltaT). The temperature
      associated with the maximum absolute value of negative ATC DeltaT is lower than
      that associated with the maximum positive ATC DeltaT. Both maximum absolute
      values of ATC DeltaTs change with the variation in the magnitude of an applied
      electric field and depend greatly on the compression intensity. 

PMID- 26307462
TI  - Antibacterial Activity and Biosensing of PVA-Lysozyme Microbubbles Formed by
      Pressurized Gyration.
AB  - In this work, the biosensing and antibacterial capabilities of PVA-lysozyme
      microbubbles have been explored. Gas-filled PVA-lysozyme microbubbles with and
      without gold nanoparticles in the diameter range of 10 to 250 MUm were produced
      using a single-step pressurized gyration process. Fluorescence microscopy showed
      the integration of gold nanoparticles on the shell of the microbubbles.
      Microbubbles prepared with gold nanoparticles showed greater optical extinction
      values than those without gold nanoparticles, and these values increased with the
      concentration of the gold nanoparticles. Both types of microbubbles showed
      antibacterial activity against Gram-negative Escherichia coli (E. coli), with the
      bubbles containing the gold nanoparticles performing better than the former. The
      conjugation of the microbubbles with alkaline phosphatase allowed the detection
      of pesticide paraoxon in aqueous solution, and this demonstrates the biosensing
      capabilities of these microbubbles. 

PMID- 26307463
TI  - Evidence that non-dreamers do dream: a REM sleep behaviour disorder model.
AB  - To determine whether non-dreamers do not produce dreams or do not recall them,
      subjects were identified with no dream recall with dreamlike behaviours during
      rapid eye movement sleep behaviour disorder, which is typically characterised by
      dream-enacting behaviours congruent with sleep mentation. All consecutive
      patients with idiopathic rapid eye movement sleep behaviour disorder or rapid eye
      movement sleep behaviour disorder associated with Parkinson's disease who
      underwent a video-polysomnography were interviewed regarding the presence or
      absence of dream recall, retrospectively or upon spontaneous arousals. The
      patients with no dream recall for at least 10 years, and never-ever recallers
      were compared with dream recallers with rapid eye movement sleep behaviour
      disorder regarding their clinical, cognitive and sleep features. Of the 289
      patients with rapid eye movement sleep behaviour disorder, eight (2.8%) patients
      had no dream recall, including four (1.4%) patients who had never ever recalled
      dreams, and four patients who had no dream recall for 10-56 years. All non
      recallers exhibited, daily or almost nightly, several complex, scenic and
      dreamlike behaviours and speeches, which were also observed during rapid eye
      movement sleep on video-polysomnography (arguing, fighting and speaking). They
      did not recall a dream following sudden awakenings from rapid eye movement sleep.
      These eight non-recallers with rapid eye movement sleep behaviour disorder did
      not differ in terms of cognition, clinical, treatment or sleep measures from the
      17 dreamers with rapid eye movement sleep behaviour disorder matched for age, sex
      and disease. The scenic dreamlike behaviours reported and observed during rapid
      eye movement sleep in the rare non-recallers with rapid eye movement sleep
      behaviour disorder (even in the never-ever recallers) provide strong evidence
      that non-recallers produce dreams, but do not recall them. Rapid eye movement
      sleep behaviour disorder provides a new model to evaluate cognitive processing
      during dreaming and subsequent recall.

PMID- 26307464
TI  - Crime and mortality in a population-based nationwide 1981 birth cohort: Results
      from the FinnCrime study.
AB  - BACKGROUND: Offending is known to be associated with various health problems and
      premature death, but previous studies on associations between offending and
      mortality have often been only with men, convicted offenders or highly selected
      samples. A more sensitive measure of offending may be preferable when trying to
      understand the extent of health disadvantages among people who offend. AIMS: The
      aim of this paper was to study the associations between investigated offending,
      death and causes of death in a nationally representative birth cohort. METHODS: A
      broad concept of offending was used such that people who had had any contact with
      the police because they had been suspected of crime were included. Offending data
      were obtained from the National Police Register for 5405 men and women born in
      Finland in 1981, spanning their ages 15-30 years; mortality data were received
      from Statistics Finland. Offending was classified into four categories by
      frequency: none, 1-4 different offence contacts, 5-27 and 28 or more. Causes of
      death were categorised into natural, accidents, suicide or homicide. Of the
      cohort, 2304 (43%) had offended and 57 (1.1%) had died. Associations between
      offending, mortality and causes of death were analysed, controlling for parental
      education level and family structure in childhood. RESULTS: The mortality rate
      was higher among offenders than non-offenders, increasing with rising frequency
      of offending. The most frequent offenders were nearly 30 times more likely to
      have died by age 30 than non-offenders (odds ratio 28.6, confidence interval 12.1
      67.5); risk was higher for female than male offenders. Death among offenders was
      less likely to be from natural causes. IMPLICATIONS: A heightened risk of
      premature death is the ultimate form of adverse outcome for offenders. Offenders'
      health is likely to need more attention as part of their overall management, for
      recidivists in particular. In our study, offenders' only certain criminal justice
      contact was with the police, so it may be that the police should take a greater
      role in signposting them towards health services. Offender treatment is needed
      not only to protect potential victims but also offenders themselves. Copyright
      (c) 2015 John Wiley & Sons, Ltd.

PMID- 26307465
TI  - Detection of Klebsiella pneumoniae co-producing NDM-7 and OXA-181, Escherichia
      coli producing NDM-5 and Acinetobacter baumannii producing OXA-23 in a single
      patient.

PMID- 26307466
TI  - Dissemination of multiresistant Enterobacter cloacae isolates producing OXA-48
      and CTX-M-15 in a Spanish hospital.
AB  - Twenty-one multiresistant Enterobacter cloacae isolates producing OXA-48 (n=10),
      CTX-M-15 (n=7) or both (n=4) beta-lactamases were detected in a Spanish hospital
      during a 1-year period (June 2013 to June 2014). The isolates were also resistant
      to non-beta-lactam antimicrobials, further complicating the therapeutic options.
      Genotyping of the isolates identified two major clones (ST74 and ST66) that
      caused prolonged outbreaks in different buildings of the hospital as well as some
      sporadic isolates (ST78, ST45 and ST295). Isolates belonging to clone 1 (n=7)
      were carbapenem-resistant and carried the bla(OXA-48) gene on a conjugative
      IncL/M plasmid of ca. 65 kb. Clone 2 isolates (n=11) were resistant to cefepime
      and harboured the bla(CTX-M-15) gene on an ca. 150-kb, non-conjugative plasmid of
      the IncF group, co-harbouring the qnrB and aac(6')-Ib-cr genes encoding quinolone
      resistance. Four clone 2 isolates were also resistant to carbapenems owing to the
      co-production of OXA-48. Most of the isolates were recovered from critically ill
      patients and were admitted to intensive care units; a single patient was
      transferred from another Spanish hospital. Intrahospital and interhospital
      dissemination of multiresistant E. cloacae isolates is of major clinical concern
      as it could lead to endemic nosocomial situations.

PMID- 26307467
TI  - Preferential decoding of emotion from human non-linguistic vocalizations versus
      speech prosody.
AB  - This study used event-related brain potentials (ERPs) to compare the time course
      of emotion processing from non-linguistic vocalizations versus speech prosody, to
      test whether vocalizations are treated preferentially by the neurocognitive
      system. Participants passively listened to vocalizations or pseudo-utterances
      conveying anger, sadness, or happiness as the EEG was recorded. Simultaneous
      effects of vocal expression type and emotion were analyzed for three ERP
      components (N100, P200, late positive component). Emotional vocalizations and
      speech were differentiated very early (N100) and vocalizations elicited stronger,
      earlier, and more differentiated P200 responses than speech. At later stages (450
      700ms), anger vocalizations evoked a stronger late positivity (LPC) than other
      vocal expressions, which was similar but delayed for angry speech. Individuals
      with high trait anxiety exhibited early, heightened sensitivity to vocal emotions
      (particularly vocalizations). These data provide new neurophysiological evidence
      that vocalizations, as evolutionarily primitive signals, are accorded precedence
      over speech-embedded emotions in the human voice.

PMID- 26307468
TI  - Source analysis of stimulus-preceding negativity constrained by functional
      magnetic resonance imaging.
AB  - The stimulus-preceding negativity (SPN) is an event-related potential (ERP)
      reflecting anticipation. The anterior insular cortex is assumed to be one of the
      physiological sources of the SPN. However, the precise neural substrates of the
      SPN have yet to be confirmed. We therefore performed separate functional magnetic
      resonance imaging (fMRI) and ERP studies using the same time estimation task,
      followed by fMRI-constrained ERP source analysis. Dipole locations were
      determined by the fMRI results, while the time courses of dipole activities were
      modeled by the ERP data. Analysis revealed that the right anterior insula was
      significantly activated before delivery of the feedback stimulus, whereas the
      left anterior insula was not, and that the SPN mainly arose from four groups of
      brain regions related to, respectively: (1) the salience network, (2) reward
      expectation, (3) perceptual anticipation, and (4) arousal. The results suggest
      that the SPN pertains to multiple brain functions with complex interactions.

PMID- 26307469
TI  - Ensemble and single-molecule biophysical characterization of D17.4 DNA aptamer
      IgE interactions.
AB  - BACKGROUND: The IgE-binding DNA aptamer 17.4 is known to inhibit the interaction
      of IgE with the high-affinity IgE Fc receptor FcepsilonRI. While this and other
      aptamers have been widely used and studied, there has been relatively little
      investigation of the kinetics and energetics of their interactions with their
      targets, by either single-molecule or ensemble methods. METHODS: The dissociation
      kinetics of the D17.4/IgE complex and the effects of temperature and ionic
      strength were studied using fluorescence anisotropy and single-molecule
      spectroscopy, and activation parameters calculated. RESULTS: The dissociation of
      D17.4/IgE complex showed a strong dependence on temperature and salt
      concentration. The koff of D17.4/IgE complex was calculated to be (2.92+/
      0.18)*10(-3) s(-1) at 50 mM NaCl, and (1.44+/-0.02)*10(-2) s(-1) at 300 mM NaCl,
      both in 1 mM MgCl2 and 25 degrees C. The dissociation activation energy for the
      D17.4/IgE complex, Ea, was 16.0+/-1.9 kcal mol(-1) at 50 mM NaCl and 1 mM MgCl2.
      Interestingly, we found that the C19A mutant of D17.4 with stabilized stem
      structure showed slower dissociation kinetics compared to D17.4. Single-molecule
      observations of surface-immobilized D17.4/IgE showed much faster dissociation
      kinetics, and heterogeneity not observable by ensemble techniques. CONCLUSIONS:
      The increasing koff value with increasing salt concentration is attributed to the
      electrostatic interactions between D17.4/IgE. We found that both the changes in
      activation enthalpy and activation entropy are insignificant with increasing NaCl
      concentration. The slower dissociation of the mutant C19A/IgE complex is likely
      due to the enhanced stability of the aptamer. GENERAL SIGNIFICANCE: The
      activation parameters obtained by applying transition state analysis to kinetic
      data can provide details on mechanisms of molecular recognition and have
      applications in drug design. Single-molecule dissociation kinetics showed greater
      kinetic complexity than was observed in the ensemble in-solution systems,
      potentially reflecting conformational heterogeneity of the aptamer. This article
      is part of a Special Issue entitled: Physiological Enzymology and Protein
      Functions.

PMID- 26307472
TI  - Ethical and well-constructed research into the surgical management of obstetric
      fistula: a distant hope or a real possibility?

PMID- 26307473
TI  - Female sexual dysfunction is an artificial concept driven by commercial
      interests: FOR: FSD is a multimillion dollar business.

PMID- 26307474
TI  - Female sexual dysfunction is an artificial concept driven by commercial
      interests: AGAINST: FSD is a real and complex problem.

PMID- 26307475
TI  - Re: Prenatal detection of congenital heart disease--results of a national
      screening programme.

PMID- 26307476
TI  - Re: Balancing the efficacy and safety of misoprostol: a meta-analysis comparing
      25 versus 50 MUg of intravaginal misoprostol for the induction of labour: Safety
      of 25-MUg intravaginal tablet of misoprostol for the induction of labour.

PMID- 26307477
TI  - Authors' reply re: Prenatal detection of congenital heart disease-results of a
      national screening programme.

PMID- 26307478
TI  - Re: How useful are national caesarean section rates for monitoring quality of
      perinatal care?Other factors affecting variation in caesarean section rates in
      other countries.

PMID- 26307479
TI  - A report from #BlueJC: When is the best time to deliver twins?

PMID- 26307480
TI  - Surface structured platinum electrodes for the electrochemical reduction of
      carbon dioxide in imidazolium based ionic liquids.
AB  - The direct CO2 electrochemical reduction on model platinum single crystal
      electrodes Pt(hkl) is studied in [C2mim(+)][NTf2(-)], a suitable room temperature
      ionic liquid (RTIL) medium due to its moderate viscosity, high CO2 solubility and
      conductivity. Single crystal electrodes represent the most convenient type of
      surface structured electrodes for studying the impact of RTIL ion adsorption on
      relevant electrocatalytic reactions, such as surface sensitive electrochemical
      CO2 reduction. We propose here based on cyclic voltammetry and in situ
      electrolysis measurements, for the first time, the formation of a stable adduct
      [C2mimH-CO2(-)] by a radical-radical coupling after the simultaneous reduction of
      CO2 and [C2mim(+)]. It means between the CO2 radical anion and the radical formed
      from the reduction of the cation [C2mim(+)] before forming the corresponding
      electrogenerated carbene. This is confirmed by the voltammetric study of a model
      imidazolium-2-carboxylate compound formed following the carbene pathway. The
      formation of that stable adduct [C2mimH-CO2(-)] blocks CO2 reduction after a
      single electron transfer and inhibits CO2 and imidazolium dimerization reactions.
      However, the electrochemical reduction of CO2 under those conditions provokes the
      electrochemical cathodic degradation of the imidazolium based RTIL. This
      important limitation in CO2 recycling by direct electrochemical reduction is
      overcome by adding a strong acid, [H(+)][NTf2(-)], into solution. Then, protons
      become preferentially adsorbed on the electrode surface by displacing the
      imidazolium cations and inhibiting their electrochemical reduction. This fact
      allows the surface sensitive electro-synthesis of HCOOH from CO2 reduction in
      [C2mim(+)][NTf2(-)], with Pt(110) being the most active electrode studied. 

PMID- 26307481
TI  - Internal tremor in Parkinson's disease, multiple sclerosis, and essential tremor.
AB  - OBJECTIVE: Internal tremor (IT) is a poorly recognized symptom that has been
      described in Parkinson's disease (PD). Described as a feeling of tremor in the
      extremities or trunk without actual movement, ITs are not debilitating but can be
      bothersome to patients. The origin of the sensation is unknown., and ITs may be
      prevalent in other diseases than PD. The present study sought to expand knowledge
      about IT by confirming their presence in PD, and determining their prevalence in
      Multiple Sclerosis (MS), and Essential Tremor (ET). METHODS: A survey was
      developed in order to determine the prevalence of IT in PD, MS, and ET and to
      learn what associations with various disease characteristics were present. The
      survey was administered to 89 consecutive PD, 70 MS, and 11 ET patients. RESULTS:
      ITs were found to be a prevalent symptom in all three disorders (32.6% of PD,
      35.9% of MS, and 54.5% of ET subjects reported experiencing ITs). ITs were found
      to be associated both with the subjects' perceived levels of anxiety and the
      presence of visible tremors. CONCLUSION: ITs appear to be a common symptom in all
      three disorders studied. These results need to be confirmed and compared to
      appropriate control populations.

PMID- 26307482
TI  - Responses to Financial Loss During the Great Recession: An Examination of Sense
      of Control in Late Midlife.
AB  - OBJECTIVES: The "Great Recession" shocked the primary institutions that help
      individuals and families meet their needs and plan for the future. This study
      examines middle-aged adults' experiences of financial loss and considers how
      socioeconomic and interpersonal resources facilitate or hinder maintaining a
      sense of control in the face of economic uncertainty. METHOD: Using the 2006 and
      2010 waves of the Health and Retirement Study, change in income and wealth,
      giving help to and receiving help from others, household complexity, and sense of
      control were measured among middle-aged adults (n = 3,850; age = 51-60 years).
      RESULTS: Socioeconomic resources predicted both the level of and change in the
      engagement of interpersonal resources prior to and during the Great Recession.
      Experiences of financial loss were associated with increased engagement of
      interpersonal resources and decreased sense of control. The effect of financial
      loss was dampened by education. Sense of control increased with giving help and
      decreased with household complexity. DISCUSSION: Findings suggest that, across
      socioeconomic strata, proportional loss in financial resources resulted in a loss
      in sense of control. However, responses to financial loss differed by
      socioeconomic status, which differentiated the ability to maintain a sense of
      control following financial loss.

PMID- 26307483
TI  - Relationships Among Nightly Sleep Quality, Daily Stress, and Daily Affect.
AB  - Objectives.: We explored the prospective, microlevel relationship between nightly
      sleep quality (SQ) and the subsequent day's stress on positive (PA) and negative
      affect (NA) as well as the moderating relationships between nightly SQ,
      subsequent stress, and subsequent PA on NA. We investigated whether age moderated
      these relationships. Method.: We collected 56 days of sleep, stress, and affect
      data using daily diary questionnaires (N = 552). We used multilevel modeling to
      assess relationships at the between- and within-person levels. Results.: Daily
      increases in SQ and decreases in stress interacted to predict higher daily PA and
      lower daily NA. Better SQ in older adults enhanced the benefits of PA on the
      stress-NA relationship more during times of low stress, whereas better sleep in
      younger adults enhanced the benefits of PA more during times of high stress.
      Between-person effects were stronger predictors of well-being outcomes than
      within-person variability. Discussion.: The combination of good SQ and higher PA
      buffered the impact of stress on NA. The moderating impact of age suggests that
      sleep and stress play different roles across adulthood. Targeting intervention
      and prevention strategies to improve SQ and enhance PA could disrupt the
      detrimental relationship between daily stress and NA.

PMID- 26307484
TI  - Living Arrangements and Psychological Well-Being of the Older Adults After the
      Economic Transition in Vietnam.
AB  - OBJECTIVES: We examine the relationship between living arrangements and
      psychological well-being of the older adults in Vietnam, where there is an
      influence of Confucian values and a lack of close substitutes for family care of
      the older adults, by exploiting a great deal of regional variation in economic
      development. We also examine the role of living arrangements in well-being
      differentials across regions. METHOD: We estimate a triangular simultaneous
      equation discrete-response model, which accounts for the simultaneity between
      living arrangements and psychological well-being (happiness, depression,
      loneliness, poor appetite, and sleep disorder), using a nationally representative
      sample of 2,225 adults aged 60 and older drawn from the 2011 Vietnam Aging
      Survey. RESULTS: Intergenerational coresidence significantly increases the
      psychological well-being of the older adults in Vietnam. The results are fairly
      robust, even after taking quasi-coresidence into account, decomposing the
      psychological well-being index into each affect and symptom, and splitting the
      sample by gender. DISCUSSION: Changes in living arrangements induced by
      differences in labor market opportunities in neighboring regions have resulted in
      significant differences in psychological well-being among the older adults. The
      findings point to the need for attention to the mental health of elderly parents
      left behind in less economically developed regions.

PMID- 26307485
TI  - The Growth of Older Inmate Populations: How Population Aging Explains Rising Age
      at Admission.
AB  - Objectives: Older inmates are the fastest growing segment of the prison
      population; however, the reasons for this are not well understood. One
      explanation is that the general population is aging, driving prison age
      distributions to change. For this article, we study the role of population aging
      in prison growth by investigating how the baby boom phenomenon of post-World War
      II has contributed to the growth of older inmate populations. Method: We identify
      the impact of population aging using simulation methods that explain prison
      growth as the combination of criminal justice processes. Results: Overall, we
      find evidence that population aging has played a significant role in explaining
      the growth of older inmate populations, in particular among inmates aged between
      50 and 64 years, contributing to as much as half of the observed increase in
      these groups since 2000. Discussion: This finding stands in contrast to the
      notion that population aging has little explanatory power in describing the
      growth of prison populations and implies that older inmate groups are more
      sensitive to compositional changes in the general population. We argue that
      prediction-based modeling of prison growth should more seriously consider the
      impacts and consequences of demographic shifts among older prisoner populations.

PMID- 26307486
TI  - Decision Support Preferences Among Hispanic and Non-Hispanic White Older Adults
      With Chronic Musculoskeletal Pain.
AB  - OBJECTIVES: Despite broad recognition that social networks play a key role in the
      management of chronic musculoskeletal pain (CMP), little is known about when and
      why older adults with CMP choose to involve others in treatment decisions. This
      study investigates the types (i.e., informational, emotional, and instrumental)
      and sources (i.e., formal and informal) of support Hispanic and non-Hispanic
      White CMP patients desire and receive when making decisions about their pain
      care. METHOD: Semi-structured interviews were conducted with Hispanic and non
      Hispanic White older adults with CMP (N = 63) recruited from one medical center
      and one senior center in New York City. Interviews were transcribed and then
      analyzed using content analysis. RESULTS: CMP patients sought network members who
      supported their emotional well-being throughout the decision-making process. When
      considering high-stakes treatment decisions, participants selectively involved
      individuals who had similar pain conditions or first-hand experience with the
      procedure. Participants' perceptions of the decision-making process were
      contingent upon the congruence between the decision they made and the support
      they received for it. For Spanish-speaking participants, positive perceptions
      were linked with satisfactory language competence by their providers. On the
      other hand, lack of language competence among providers hindered Spanish
      speakers' ability to obtain adequate informational support. DISCUSSION: Results
      reveal the importance of empathic patient-provider exchanges across diverse
      patient populations and cultural sensitivity for Spanish-speaking patients.
      Findings suggest that social networks beyond the patient-provider dyad influence
      patients' decision-making satisfaction.

PMID- 26307487
TI  - Gender, Illness-Related Diabetes Social Support, and Glycemic Control Among
      Middle-Aged and Older Adults.
AB  - OBJECTIVES: This study examined whether the association between illness-related
      diabetes social support (IRDSS) and glycemic control among middle-aged and older
      adults is different for men and women. METHOD: This cross-sectional analysis
      included 914 adults with diabetes who completed the Health and Retirement Study's
      2003 Mail Survey on Diabetes. IRDSS is a composite score of 8 diabetes self-care
      measures. Hemoglobin A1c levels were obtained to measure good glycemic control
      (<8.0%). Gender-stratified multivariate log-binomial regression models were used
      to estimate prevalence ratios and examine the association between IRDSS and
      glycemic control after controlling for sociodemographic, lifestyle, and clinical
      characteristics. RESULTS: The prevalence of good glycemic control was 48.9% among
      women and 51.1% among men. Mean composite IRDSS scores did not differ by gender.
      Among women, composite IRDSS was associated with adequate glycemic control
      (prevalence ratio: 1.06; 95% confidence interval: 1.02, 1.08), and all individual
      components of IRDSS, with the exception of keeping appointments, were positively
      associated with adequate glycemic control. No significant associations were
      observed in men for composite or individual components of IRDSS. DISCUSSION:
      Determining the gender-specific impact derived from IRDSS is a worthwhile
      approach to highlighting factors that differentially predict optimal glycemic
      control among middle-aged and older adults.

PMID- 26307488
TI  - Predictors of Self-Rated Health: Does Education Play a Role Above and Beyond Age?
AB  - Objectives: Previous studies have demonstrated that while health factors lose
      importance for the individual conceptualization of self-rated health (SRH) with
      advancing age, subjective well-being (SWB) factors gain in importance. The
      present study examined whether this age-related pattern differs between
      educational groups. Method: Longitudinal data of adults aged 40 years and older
      of the German Ageing Survey was used (N = 6,812). The role of education in age
      related changes in the predictive value of different health and SWB facets for
      SRH was investigated with a cross-lagged panel regression model. Results:
      Physical conditions were a stronger predictor in lower than in higher educated
      individuals while the associationdid not change with age. In contrast, positive
      affect and life satisfaction only gained in importance with advancing age for
      higher educated individuals. Negative affect was an equally strong predictor
      independent of education, and loneliness had a stronger association with SRH in
      people with lower education compared to those with high education while the
      associations did not change with age. Discussion: The findings highlight the
      importance of considering the multidimensionality of SWB and the educational
      background of individuals for the study of SRH and indicate possible limits to
      adjustment to age-related declines in health.

PMID- 26307489
TI  - Older Adults' Attitudes Toward Cohabitation: Two Decades of Change.
AB  - OBJECTIVES: Our study tracks cohort change in the attitudes of adults aged 50 and
      older toward cohabitation from 1994 to 2012. METHOD: We used data from the 1994,
      2002, and 2012 waves of the General Social Survey to examine the roles of cohort
      replacement and intracohort change in the trend toward favorable cohabitation
      attitudes and to examine sociodemographic variation in patterns of support for
      cohabitation. RESULTS: Support for cohabitation accelerated over time with nearly
      half (46%) of older adults reporting favorable attitudes toward cohabitation in
      2012 versus just 20% in 1994. This shift in older adults' attitudes largely
      reflected cohort replacement rather than intracohort change. Some of the factors
      associated with later life cohabitation experience were linked to supportive
      attitudes. DISCUSSION: Cohort succession is fueling the growing acceptance of
      cohabitation among older adults and coincides with the rapid growth in later life
      cohabitation that has occurred in recent decades.

PMID- 26307490
TI  - Modulation of GABAA receptors by neurosteroids. A new concept to improve
      cognitive and motor alterations in hepatic encephalopathy.
AB  - Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome affecting
      patients with liver diseases, mainly those with liver cirrhosis. The mildest form
      of HE is minimal HE (MHE), with mild cognitive impairment, attention deficit,
      psychomotor slowing and impaired visuo-motor and bimanual coordination. MHE may
      progress to clinical HE with worsening of the neurological alterations which may
      lead to reduced consciousness and, in the worse cases, may progress to coma and
      death. HE affects several million people in the world and is a serious health,
      social and economic problem. There are no specific treatments for the
      neurological alterations in HE. The mechanisms underlying the cognitive and motor
      alterations in HE are beginning to be clarified in animal models. These studies
      have allowed to design and test in animal models of HE new therapeutic approaches
      which have successfully restored cognitive and motor function in rats with HE. In
      this article we review the evidences showing that. 

PMID- 26307493
TI  - Immunomodulatory potential of a brewers' spent grain protein hydrolysate
      incorporated into low-fat milk following in vitro gastrointestinal digestion.
AB  - Brewers' spent grain (BSG) protein rich fraction was previously hydrolysed using
      Alcalase (U) and three additional fractions were prepared by membrane
      fractionation; a 5-kDa retentate (U > 5), a 5-kDa permeate (U < 5) and a 3-kDa
      permeate (U < 3). In the present study, these fractions were added to milk,
      subjected to simulated gastrointestinal digestion (SGID) and their anti
      inflammatory potential was investigated. The digestates caused a significant
      reduction (p < 0.05) in interleukin-6 (IL-6) production in Concanavalin-A (ConA)
      stimulated Jurkat T cells. The samples did not significantly alter the production
      of IL-6 in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. IL-2 and
      interferon-gamma (IFN-gamma) production in stimulated Jurkat T cells and IL-1beta
      and tumor necrosis factor-alpha (TNF-alpha) production in stimulated RAW 264.7
      cells were not affected in the presence of the digestates. Results show that a
      SGID milk product supplemented with BSG hydrolysate and its associated
      ultrafiltered fractions can confer anti-inflammatory effects in Jurkat T cells. 

PMID- 26307492
TI  - White matter integrity of cerebellar-cortical tracts in reading impaired
      children: A probabilistic tractography study.
AB  - Little is known about the white matter integrity of cerebellar-cortical pathways
      in individuals with dyslexia. Building on previous findings of decreased volume
      in the anterior lobe of the cerebellum, we utilized novel cerebellar segmentation
      procedures and probabilistic tractography to examine tracts that connect the
      anterior lobe of the cerebellum and cortical regions typically associated with
      reading: the temporoparietal (TP), occipitotemporal (OT), and inferior frontal
      (IF) regions. The sample included 29 reading impaired children and 27 typical
      readers. We found greater fractional anisotropy (FA) for the poor readers in
      tracts connecting the cerebellum with TP and IF regions relative to typical
      readers. In the OT region, FA was greater for the older poor readers, but smaller
      for the younger ones. This study provides evidence for discrete, regionally-bound
      functions of the cerebellum and suggests that projections from the anterior
      cerebellum appear to have a regulatory effect on cortical pathways important for
      reading.

PMID- 26307491
TI  - Assessment of sex specific endocrine disrupting effects in the prenatal and pre
      pubertal rodent brain.
AB  - BACKGROUND: Brain sex differences are found in nearly every region of the brain
      and fundamental to sexually dimorphic behaviors as well as disorders of the brain
      and behavior. These differences are organized during gestation and early
      adolescence and detectable prior to puberty. Endocrine disrupting compounds
      (EDCs) interfere with hormone action and are thus prenatal exposure is
      hypothesized to disrupt the formation of sex differences, and contribute to the
      increased prevalence of pediatric neuropsychiatric disorders that present with a
      sex bias. OBJECTIVE: Available evidence for the ability of EDCs to impact the
      emergence of brain sex differences in the rodent brain was reviewed here, with a
      focus on effects detected at or before puberty. METHODS: The peer-reviewed
      literature was searched using PubMed, and all relevant papers published by
      January 31, 2015 were incorporated. Endpoints of interest included molecular
      cellular and neuroanatomical effects. Studies on behavioral endpoints were not
      included because numerous reviews of that literature are available. RESULTS: The
      hypothalamus was found to be particularly affected by estrogenic EDCs in a sex,
      time, and exposure dependent manner. The hippocampus also appears vulnerable to
      endocrine disruption by BPA and PCBs although there is little evidence from the
      pre-pubertal literature to make any conclusions about sex-specific effects.
      Gestational EDC exposure can alter fetal neurogenesis and gene expression
      throughout the brain including the cortex and cerebellum. The available
      literature primarily focuses on a few, well characterized EDCs, but little data
      is available for emerging contaminants. CONCLUSION: The developmental EDC
      exposure literature demonstrates evidence of altered neurodevelopment as early as
      fetal life, with sex specific effects observed throughout the brain even before
      puberty.

PMID- 26307494
TI  - Early onset Charcot-Marie-Tooth neuropathy type 2A and severe developmental
      delay: expanding the clinical phenotype of MFN2-related neuropathy.
AB  - Charcot-Marie-Tooth (CMT) syndromes are a group of clinically heterogeneous
      disorders of the peripheral nervous system. Mutations of mitofusin 2 (MFN2) have
      been recognized to be associated with CMT type 2A (CMT2A). CMT2A is primarily an
      axonal disorder resulting in motor and sensory neuropathy. We report a male child
      with psychomotor delay, dysmorphic features, and weakness of lower limbs
      associated with electrophysiological features of severe, sensory-motor, axonal
      neuropathy. The patient was diagnosed with early onset CMT2A and severe
      psychomotor retardation associated with c.310C>T mutation (p.R104W) in MFN2 gene.
      CMT2A should be considered in patients with both axonal sensory-motor neuropathy
      and developmental delay. 

PMID- 26307495
TI  - A proteomic map of the unsequenced kala-azar vector Phlebotomus papatasi using
      cell line.
AB  - The debilitating disease kala-azar or visceral leishmaniasis is caused by the
      kinetoplastid protozoan parasite Leishmania donovani. The parasite is transmitted
      by the hematophagous sand fly vector of the genus Phlebotomus in the old world
      and Lutzomyia in the new world. The predominant Phlebotomine species associated
      with the transmission of kala-azar are Phlebotomus papatasi and Phlebotomus
      argentipes. Understanding the molecular interaction of the sand fly and
      Leishmania, during the development of parasite within the sand fly gut is crucial
      to the understanding of the parasite life cycle. The complete genome sequences of
      sand flies (Phlebotomus and Lutzomyia) are currently not available and this
      hinders identification of proteins in the sand fly vector. The current study
      utilizes a three frame translated transcriptomic data of P. papatasi in the
      absence of genomic sequences to analyze the mass spectrometry data of P. papatasi
      cell line using a proteogenomic approach. Additionally, we have carried out the
      proteogenomic analysis of P. papatasi by comparative homology-based searches
      using related sequenced dipteran protein data. This study resulted in the
      identification of 1313 proteins from P. papatasi based on homology. Our study
      demonstrates the power of proteogenomic approaches in mapping the proteomes of
      unsequenced organisms. 

PMID- 26307497
TI  - Prevalence and clinical correlates of police contact prior to a first diagnosis
      of schizophrenia.
AB  - BACKGROUND: Little is known about the reasons why people with schizophrenia have
      contact with police, especially prior to the first episode of illness. AIM: To
      investigate the prevalence and correlates of police contact in first-episode
      schizophrenia. METHODS: The prevalence and type of police contact was established
      among all 110 patients presenting to psychiatric services in one catchment area
      during a first episode of schizophrenia and among 65 non-mentally ill controls,
      by participant and collateral interview and from records. Socio-demographic and
      clinical characteristics were also recorded and the two groups compared. RESULTS:
      The first episode of schizophrenia patients had more contact with police than
      controls, despite the higher prevalence of conduct disorder symptoms among the
      controls. The patients were not, however, more likely to be incarcerated or
      arrested. Among the patients, over half of the police call-outs occurred during
      the period of untreated psychosis. Positive psychotic symptoms were independently
      associated with police contact, after allowing for socio-demographics.
      CONCLUSIONS: As over a third of people in a first episode of schizophrenia had
      been in contact with the police - more than twice the proportion among non
      psychotic controls - and contact was associated with untreated positive psychotic
      symptoms, better early detection and treatment of psychosis seems indicated. In
      the meantime, police services may be playing an important role in reducing the
      duration of untreated psychosis. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 26307496
TI  - Susceptibility profile of Aedes aegypti from Santiago Island, Cabo Verde, to
      insecticides.
AB  - In 2009, Cabo Verde diagnosed the first dengue cases, with 21,137 cases reported
      and Aedes aegypti was identified as the vector. Since the outbreak, chemical
      insecticides and source reduction were used to control the mosquito population.
      This study aimed to assess the susceptibility of A. aegypti populations from
      Santiago, Cabo Verde to insecticides and identify the mechanisms of resistance.
      Samples of A. aegypti eggs were obtained at two different time periods (2012 and
      2014), using ovitraps in different locations in Santiago Island to establish the
      parental population. F1 larvae were exposed to different concentrations of
      insecticides (Bacillus thuringiensis var israelensis (Bti), diflubenzuron and
      temephos) to estimate the lethal concentrations (LC90) and calculate the
      respective rate of resistance (RR90). Semi-field tests using temephos-ABATE((r))
      were performed to evaluate the persistence of the product. Bottle tests using
      female mosquitoes were carried out to determine the susceptibility to the
      adulticides malathion, cypermethrin and deltamethrin. Biochemical and molecular
      tests were performed to investigate the presence of metabolic resistance
      mechanisms, associated with the enzymes glutathione S-transferases (GSTs),
      esterases and mixed-function oxidases (MFO) and to detect mutations or
      alterations in the sodium channel and acetylcholinesterase genes. A. aegypti
      mosquitoes from Santiago exhibited resistance to deltamethrin, cypermethrin
      (mortality<80%) and temephos (RR90=4.4) but susceptibility to malathion
      (mortality>=98%), Bti and diflubenzuron. The low level of resistance to temephos
      did not affect the effectiveness of Abate((r)). The enzymatic analysis conducted
      in 2012 revealed slight changes in the activities of GST (25%), MFO (18%), alpha
      esterase (19%) and beta-esterase (17%), but no significant changes in 2014.
      Target site resistance mutations were not detected. Our results suggest that the
      A. aegypti population from Santiago is resistant to two major insecticides used
      for vector control, deltamethrin and temephos. To our knowledge, this is the
      first report of temephos resistance in an African A. aegypti population. The low
      level of temephos resistance was maintained from 2012-2014, which suggested the
      imposition of selective pressure, although it was not possible to identify the
      resistance mechanisms involved. These data show that the potential failures in
      the local mosquito control program are not associated with insecticide
      resistance. 

PMID- 26307498
TI  - A qualitative review of sports concussion education: prime time for evidence
      based knowledge translation.
AB  - BACKGROUND: Educating athletes, coaches, parents and healthcare providers about
      concussion management is a public health priority. There is an abundance of
      information on sports concussions supported by position statements from governing
      sport and medical organisations. Yet surveys of athletes, parents, coaches and
      healthcare providers continue to identify multiple barriers to the successful
      management of sports concussion. To date, efforts to provide education using
      empirically sound methodologies are lacking. PURPOSE: To provide a comprehensive
      review of scientific research on concussion education efforts and make
      recommendations for enhancing these efforts. STUDY DESIGN: Qualitative literature
      review of sports concussion education. METHODS: Databases including PubMed, Sport
      Discus and MEDLINE were searched using standardised terms, alone and in
      combination, including 'concussion', 'sport', 'knowledge', 'education' and
      'outcome'. RESULTS: Studies measuring the success of education interventions
      suggest that simply presenting available information may help to increase
      knowledge about concussions, but it does not produce long-term changes in
      behaviour among athletes. Currently, no empirical reviews have evaluated the
      success of commercially available sports concussion applications. The most
      successful education efforts have taken steps to ensure materials are user
      friendly, interactive, utilise more than one modality to present information and
      are embedded in mandated training programmes or support legislation. Psychosocial
      theory-driven methods used to understand and improve 'buy in' from intended
      audiences have shown promise in changing behaviour. CONCLUSIONS: More deliberate
      and methodologically sound steps must be taken to optimise education and
      knowledge translation efforts in sports concussion.

PMID- 26307500
TI  - Strain glass state as the boundary of two phase transitions.
AB  - A strain glass state was found to be located between B2-B19' (cubic to
      monoclinic) phase transition and B2-R (cubic to rhombohedral) phase transition in
      Ti49Ni51 alloys after aging process. After a short time aging, strong strain
      glass transition was observed, because the size of the precipitates is small,
      which means the strain field induced by the precipitates is isotropic and point
      defect-like, and the distribution of the precipitates is random. After a long
      time aging, the average size of the precipitates increases. The strong strain
      field induced by the precipitates around them forces the symmetry of the matrix
      materials to conform to the symmetry of the crystalline structure of the
      precipitates, which results in the new phase transition. The experiment shows
      that there exists no well-defined boundary in the evolution from the strain glass
      transition to the new phase transition. Due to its generality, this glass
      mediated phase transition divergence scheme can be applied to other proper
      material systems to induce a more important new phase transition path, which can
      be useful in the field of phase transition engineering. 

PMID- 26307499
TI  - Tumor and organ uptake of (64)Cu-labeled MORAb-009 (amatuximab), an anti
      mesothelin antibody, by PET imaging and biodistribution studies.
AB  - OBJECTIVES: To investigate the effect of the injection dose of MORAb-009
      (amatuximab, an anti-mesothelin monoclonal antibody), the tumor size and the
      level of shed mesothelin on the uptake of the antibody in mesothelin-positive
      tumor and organs by biodistribution (BD) and positron emission tomography (PET)
      imaging studies. METHODS: 2-S-(4-Isothiocyanatobenzyl)-1,4,7-triazacyclononane
      1,4,7-triacetic acid (p-SCN-Bn-NOTA) was conjugated to amatuximab and labeled
      with (64)CuCl2 in 0.25 M acetate buffer, pH4.2. The resulting (64)Cu-NOTA
      amatuximab was purified with a PD 10 column. To investigate the dose effect or
      the effect of tumor size, the BD was performed in groups of nude mice (n=5) with
      mesothelin-expressing A431/H9 tumors (range, 80-300 mm(3)) one day after iv
      injection of (64)Cu-NOTA-amatuximab (10 MUCi) containing a total amatuximab dose
      of 2, 30, or 60 MUg. The BD and PET imaging were also investigated 3, 24 and 48 h
      after injecting a total dose of 30 MUg (10 MUCi for BD), and 2 or 60 MUg (300
      MUCi for PET), respectively. RESULTS: Comparing the results of the BDs from three
      different injection doses, the major difference was shown in the uptake (%ID/g)
      of the radiolabel in tumor, liver and blood. The tumor uptake and blood retention
      from 30 and 60 MUg doses were greater than those from 2 MUg dose, whereas the
      liver uptake was smaller. The BD studies also demonstrated a positive correlation
      between tumor size (or the level of shed mesothelin in blood) and liver uptake.
      However, there was a negative correlation between tumor size (or the shed
      mesothelin level) and tumor uptake and between tumor size and blood retention.
      These findings were confirmed by the PET imaging study, which clearly visualized
      the tumor uptake with the radiolabel concentrated in the tumor core and produced
      a tumor to liver ratio of 1.2 at 24h post-injection with 60 MUg amatuximab,
      whereas the injection of 2 MUg amatuximab produced a tumor to liver ratio of 0.4
      at 24h post-injection. CONCLUSION: Our studies using a nude mouse model of
      A431/H9 tumor demonstrated that the injection of a high amatuximab dose (30 to 60
      MUg) could provide a beneficial effect in maximizing tumor uptake while
      maintaining minimum liver and spleen uptakes of the radiolabel, and in
      facilitating its penetration into the tumor core.

PMID- 26307501
TI  - Vaginal birth after caesarean and home birth: a bad combination.

PMID- 26307502
TI  - Preparation and characterization of laser cladding wollastonite derived
      bioceramic coating on titanium alloy.
AB  - The bioceramic coating is fabricated on titanium alloy (Ti6Al4V) by laser
      cladding the preplaced wollastonite (CaSiO3) powders. The coating on Ti6Al4V is
      characterized by x-ray diffraction, scanning electron microscopy coupled with
      energy dispersive spectroscopy, and attenuated total reflection Fourier-transform
      infrared. The interface bonding strength is measured using the stretching method
      using an RGD-5-type electronic tensile machine. The microhardness distribution of
      the cross-section is determined using an indentation test. The in vitro
      bioactivity of the coating on Ti6Al4V is evaluated using the in vitro simulated
      body fluid (SBF) immersion test. The microstructure of the laser cladding sample
      is affected by the process parameters. The coating surface is coarse, accidented,
      and microporous. The cross-section microstructure of the ceramic layer from the
      bottom to the top gradually changes from cellular crystal, fine cellular-dendrite
      structure to underdeveloped dendrite crystal. The coating on Ti6Al4V is composed
      of CaTiO3, CaO, alpha-Ca2SiO4, SiO2, and TiO2. After soaking in the SBF solution,
      the calcium phosphate layer is formed on the coating surface. 

PMID- 26307503
TI  - Graphical methods for the analysis of shear-induced detachment of cells and
      microorganisms.
AB  - Treating shear stress induced detachment of micro-organisms as a bond breaking
      mechanism, the authors present three intuitive graphical approaches to determine
      the relevant parameters in the Arrhenius rate equation, i.e., attachment energy,
      prefactor, and maximum shear stress. They demonstrate the methods with the
      detachment of polystyrene spheres and show that having three different methods
      presents the opportunity to check the consistency of the results. 

PMID- 26307504
TI  - Minimal residual disease in cancer therapy--Small things make all the difference.
AB  - Minimal residual disease (MRD) is a major hurdle in the eradication of malignant
      tumors. Despite the high sensitivity of various cancers to treatment, some
      residual cancer cells persist and lead to tumor recurrence and treatment failure.
      Obvious reasons for residual disease include mechanisms of secondary therapy
      resistance, such as the presence of mutant cells that are insensitive to the
      drugs, or the presence of cells that become drug resistant due to activation of
      survival pathways. In addition to such unambiguous resistance modalities, several
      patients with relapsing tumors do not show refractory disease and respond again
      when the initial therapy is repeated. These cases cannot be explained by the
      selection of mutant tumor cells, and the precise mechanisms underlying this
      clinical drug resistance are ill-defined. In the current review, we put special
      emphasis on cell-intrinsic and -extrinsic mechanisms that may explain mechanisms
      of MRD that are independent of secondary therapy resistance. In particular, we
      show that studying genetically engineered mouse models (GEMMs), which highly
      resemble the disease in humans, provides a complementary approach to understand
      MRD. In these animal models, specific mechanisms of secondary resistance can be
      excluded by targeted genetic modifications. This allows a clear distinction
      between the selection of cells with stable secondary resistance and mechanisms
      that result in the survival of residual cells but do not provoke secondary drug
      resistance. Mechanisms that may explain the latter feature include special
      biochemical defense properties of cancer stem cells, metabolic peculiarities such
      as the dependence on autophagy, drug-tolerant persisting cells, intratumoral
      heterogeneity, secreted factors from the microenvironment, tumor vascularization
      patterns and immunosurveillance-related factors. We propose in the current review
      that a common feature of these various mechanisms is cancer cell dormancy.
      Therefore, dormant cancer cells appear to be an important target in the attempt
      to eradicate residual cancer cells, and eventually cure patients who repeatedly
      respond to anticancer therapy but lack complete tumor eradication. 

PMID- 26307505
TI  - Vitamin D Status in South Africa and Tuberculosis.
AB  - According to the World Health Organisation South Africa has the third highest
      tuberculosis (TB) incidence in the world, with an estimated 60 % incident cases
      having both TB and HIV. The South African National Tuberculosis Association
      (SANTA) recognized the importance of nutrition in the prevention and management
      of TB by including feeding schemes in community outreach programs. Vitamin D
      enhances innate immunity against mycobacterial infection through the
      antimicrobial peptide, cathelicidin. We reviewed studies on vitamin D status, its
      link with TB, and potential use in therapy in multiethnic South Africa with
      sunlight as primary source of vitamin D. Ethnicity, season, disease state,
      latitude, and urbanization are critical factors to be considered in vitamin D
      supplementation for prevention and treatment of TB.

PMID- 26307506
TI  - Clinical Features and Outcomes of Respiratory Complications in Patients with
      Thoracic Hyperkyphosis.
AB  - INTRODUCTION: There are few data about thoracic hyperkyphosis which focused on
      respiratory events and prognoses. We investigated the clinical features and
      outcomes of respiratory complications requiring hospitalization in patients with
      thoracic hyperkyphosis. METHODS: Following a retrospective review of the medical
      records between 2002 and 2011, we included 51 patients with thoracic
      hyperkyphosis who had visited the respiratory department due to respiratory
      symptoms. RESULTS: Of total 51 patients, 35 patients were hospitalized due to
      respiratory events. Among 56 total hospitalized events, acute respiratory failure
      (ARF) (n = 18) and exacerbation of a chronic airway disorder (n = 18) were the
      most common causes. Respiratory events related mortality was 13.7 % (7/51). The
      median value of the thoracic kyphosis angle was 89.0 degrees . The ratio of the
      measured kyphosis angle to the normal value according to age and sex showed the
      median value of 2.38 (interquartile range 1.61-2.87). This ratio was negatively
      correlated with both predicted forced vital capacity (gamma = -0.647, p < 0.0001)
      and predicted forced expiratory volume for 1 s (gamma = -0.518, p = 0.008). After
      adjustments for age and sex, hyperkyphosis (angle >=90 degrees ) was not found to
      influence the development of ARF (hazard ratio 3.2; 95 % confidence interval,
      0.86-12.14; p = 0.082). CONCLUSIONS: Patients with thoracic hyperkyphosis
      presenting to a respiratory department with respiratory issues commonly
      experienced respiratory events requiring hospitalization and had a poor
      prognosis. In addition, the severity of the kyphosis angle was correlated with
      respiratory insufficiency although it was not a risk factor for the development
      of ARF.

PMID- 26307507
TI  - Diagnostic Accuracy of Quantitative Sensory Testing to Discriminate Inflammatory
      Toothache and Intraoral Neuropathic Pain.
AB  - INTRODUCTION: A differential diagnosis between inflammatory toothache (IT) and
      intraoral neuropathic pain is challenging. The aim of this diagnostic study was
      to quantify somatosensory function of subjects with IT (acute pulpitis) and
      atypical odontalgia (AO, intraoral neuropathic pain) and healthy volunteers and
      to quantify how accurately quantitative sensory testing (QST) discriminates an IT
      or AO diagnosis. METHODS: The sample consisted of 60 subjects equally divided (n
      = 20) into 3 groups: (1) IT, (2) AO, and (3) control. A sequence of 4 QST methods
      was performed over the dentoalveolar mucosa in the apical maxillar or mandibular
      area: mechanical detection threshold, pain detection threshold (PDT), dynamic
      mechanical allodynia, and temporal summation. One-way analysis of variance, Tukey
      post hoc analyses, and z score transformation were applied to the data. In
      addition, the receiver operating characteristic curve analysis, diagnostic
      accuracy, sensitivity, specificity, likelihood ratios, and diagnostic odds ratio
      of the QST methods were calculated (alpha = 5%). RESULTS: Somatosensory
      abnormalities were found for the AO group, which is consistent with a low
      detection threshold to touch and pain and the presence of mechanical allodynia.
      For the IT group, no somatosensory abnormality was observed when compared with
      the control group. The most accurate QST to discriminate the diagnostic
      differences between IT and healthy individuals is the PDT. The diagnostic
      differences between AO and healthy individuals and between IT and AO are best
      discriminated with the mechanical detection threshold, PDT, and dynamic
      mechanical allodynia. CONCLUSIONS: The proposed QST methods may aid in the
      differential diagnosis between IT and AO with strong accuracy and may be used as
      complementary diagnostic tests.

PMID- 26307508
TI  - Influence of Endodontic Treatment and Coronal Restoration on Status of Periapical
      Tissues: A Cone-beam Computed Tomographic Study.
AB  - INTRODUCTION: This cross-sectional study determined the prevalence of apical
      radiolucency in 1290 root canal-treated teeth and the correlation between
      endodontic treatment quality and the presence of coronal restorations with apical
      radiolucency using cone-beam computed tomographic imaging. METHODS: Cone-beam
      computed tomographic scans were analyzed, and teeth were classified as healthy or
      diseased according to the periapical status. Other factors were also evaluated
      for their association with the apical diagnosis including sex, quality of
      endodontic treatment, presence of coronal restorations and posts, and apical
      level of filling. RESULTS: Of the treated teeth, 48.83% were classified as
      healthy. Only 55.11% of the teeth had endodontic treatment rated as adequate. The
      quality of endodontic treatment and the presence of coronal restoration were
      statistically correlated with the presence or absence of an apical radiolucency
      (P < .0001). Combined data revealed that teeth with both adequate endodontic
      treatment and the presence of coronal restoration showed significantly better
      apical status than the other combinations (P < .001). Canals filled up to 0-2 mm
      short of the apex had a significantly higher number of teeth rated as healthy
      compared with overfilled or underfilled cases (P = .001). The presence of a post
      was not found to be a statistical significant factor (P = .81). CONCLUSIONS: Data
      showed a relatively high prevalence of apical radiolucencies in root canal
      treated teeth. The quality of the endodontic treatment, the presence of coronal
      restoration, and apical extent of the root canal filling were significantly
      associated with healthy apical tissues.

PMID- 26307509
TI  - Histologic Assessment of Quick-Set and Mineral Trioxide Aggregate Pulpotomies in
      a Canine Model.
AB  - INTRODUCTION: Quick-Set (Primus Consulting, Bradenton, FL) is a calcium
      aluminosilicate cement that is a potential alternative to mineral trioxide
      aggregate (MTA) with greater acid resistance and faster setting. The purpose of
      this study was to compare the effects of Quick-Set and MTA on pulpal tissues in
      response to pulpotomy procedures. METHODS: The pulp chambers of 42 maxillary
      teeth in 7 beagle dogs were accessed, and the coronal pulpal tissue was removed.
      Pulpotomy procedures were performed, placing the experimental materials directly
      over the radicular pulp tissues. The dogs were sacrificed at 70 days, and the
      teeth and surrounding tissues were removed and prepared for histologic analysis.
      The sections of the pulpotomy areas were scored for inflammation, pulp tissue
      organization, reactionary dentin formation, and quality of dentinogenesis.
      RESULTS: The Quick-Set group exhibited significantly more pulpal inflammation (P
      = .002) and significantly less pulp tissue organization (P = .004). No
      significant difference was noted for reactionary dentin formation (P = .526) and
      quality of dentinogenesis (P = .436). CONCLUSIONS: Compared with ProRoot White
      MTA (Dentsply Tulsa Dental Specialties, Tulsa, OK), Quick-Set exhibited more
      pulpal inflammation and decreased pulp tissue organization. No significant
      differences were noted for reactionary dentin formation and quality of
      dentinogenesis.

PMID- 26307510
TI  - Investigation of the effects of soluble fibers on the absorption of resveratrol
      and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PHIP) in the Caco-2 cellular
      model of intestinal absorption.
AB  - Soluble fibers are known to modulate intestinal absorption of non-polar compounds
      in the small intestine. Little is known about the modulation of absorption of
      more polar compounds. In the present study, we applied the Caco-2-transwell
      system in order to investigate the modulation of intestinal bioavailability by
      soluble fibers. The system was tested using pectin and carrageenan as model
      soluble fibers at a concentration of 0.1% (w/v), which did not compromise the
      integrity of the cell monolayer. Modulation of absorption was evaluated for the
      heterocyclic amine aromatic 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
      (PHIP) and the polyphenol resveratrol. Neither pectin nor carrageenan reduced the
      high flux of PHIP, apparent permeability coefficient (Papp) of 16 * 10(-6) cm s(
      1). The low Papp of resveratrol was reduced by both soluble fibers, particularly
      by pectin. These results suggest that the low bioavailability of polyphenols
      could be further reduced by soluble fibers. Because of their co-occurrence in
      several fruits, these findings warrant further research. 

PMID- 26307511
TI  - Low-Frequency Repetitive Transcranial Magnetic Stimulation Targeted to Premotor
      Cortex Followed by Primary Motor Cortex Modulates Excitability Differently Than
      Premotor Cortex or Primary Motor Cortex Stimulation Alone.
AB  - OBJECTIVES: The excitability of primary motor cortex (M1) can be modulated by
      applying low-frequency repetitive transcranial magnetic stimulation (rTMS) over
      M1 or premotor cortex (PMC). A comparison of inhibitory effect between the two
      locations has been reported with inconsistent results. This study compared the
      response secondary to rTMS applied over M1, PMC, and a combined PMC + M1
      stimulation approach which first targets stimulation over PMC then M1. MATERIALS
      AND METHODS: Ten healthy participants were recruited for a randomized, cross-over
      design with a one-week washout between visits. Each visit consisted of a pretest,
      an rTMS intervention, and a post-test. Outcome measures included short interval
      intracortical inhibition (SICI), intracortical facilitation (ICF), and cortical
      silent period (CSP). Participants received one of the three interventions in
      random order at each visit including: 1-Hz rTMS at 90% of resting motor threshold
      to: M1 (1200 pulses), PMC (1200 pulses), and PMC + M1 (600 pulses each, 1200
      total). RESULTS: PMC + M1 stimulation resulted in significantly greater
      inhibition than the other locations for ICF (P = 0.005) and CSP (P < 0.001); for
      SICI, increased inhibition (group effect) was not observed after any of the three
      interventions, and there was no significant difference between the three
      interventions. CONCLUSION: The results indicate that PMC + M1 stimulation may
      modulate brain excitability differently from PMC or M1 alone. CSP was the
      assessment measure most sensitive to changes in inhibition and was able to
      distinguish between different inhibitory protocols. This work presents a novel
      procedure that may have positive implications for therapeutic interventions.

PMID- 26307513
TI  - Corneal Cross-linking to Halt the Progression of Keratoconus and Corneal Ectasia:
      Seven-Year Follow-up.
AB  - PURPOSE: To determine long-term efficacy and safety of riboflavin/ultraviolet A
      corneal cross-linking (CXL). DESIGN: Prospective cohort study. METHODS: Thirty
      six patients (36 eyes) who underwent epithelium-off CXL at a University Hospital
      (Guy's and St Thomas' National Health Service Foundation Trust) 6-8 years
      previously were examined. The main outcome measures were refractive error, visual
      acuity, corneal topographic keratometry, ultrasonic pachymetry, and topography
      derived corneal wavefront. RESULTS: At 7 years compared to preoperative values,
      mean spherical equivalent refractive error (SEQ) increased by +0.78 diopter (D)
      (P < .005) and mean simulated topographic keratometry (SimK) and mean maximum
      keratometry (Kmax) reduced by -0.74 D (P < .0001) and -0.91 D (P < .0001),
      respectively. Uncorrected distance acuity (UCDA) (P < .0005) and corrected
      distance acuity (CDVA) (P < .0001) had improved and root mean square (RMS) (P <
      .0005), coma (P < .0005), and secondary astigmatism (P < .005) lessened. At 7
      years compared to 1 year, CDVA improved (P < .05); mean SimK (P < .0005) and mean
      Kmax (P < .005) reduced by -0.45 D and -0.56 D, respectively; and RMS (P < .0005)
      and coma (P < .0005) decreased. At 7 years compared to 5 years, CDVA improved (P
      < .05) and trefoil reduced (P < .05). No treated eyes progressed. In 29 initially
      untreated fellow eyes mean SimK increased by +0.54 D (P < .02), mean Kmax by
      +0.87 D (P < .05), and refractive astigmatism increased (P < .0005). CONCLUSIONS:
      Following corneal cross-linking, improvements in topographic and wavefront
      parameters evident at 1 year were seen to continue to improve at 5 years and were
      maintained at 7 years. No treated eyes progressed over the 7-year follow-up
      period.

PMID- 26307512
TI  - Assessing Electronic Cigarette-Related Tweets for Sentiment and Content Using
      Supervised Machine Learning.
AB  - BACKGROUND: Electronic cigarettes (e-cigarettes) continue to be a growing topic
      among social media users, especially on Twitter. The ability to analyze
      conversations about e-cigarettes in real-time can provide important insight into
      trends in the public's knowledge, attitudes, and beliefs surrounding e
      cigarettes, and subsequently guide public health interventions. OBJECTIVE: Our
      aim was to establish a supervised machine learning algorithm to build predictive
      classification models that assess Twitter data for a range of factors related to
      e-cigarettes. METHODS: Manual content analysis was conducted for 17,098 tweets.
      These tweets were coded for five categories: e-cigarette relevance, sentiment,
      user description, genre, and theme. Machine learning classification models were
      then built for each of these five categories, and word groupings (n-grams) were
      used to define the feature space for each classifier. RESULTS: Predictive
      performance scores for classification models indicated that the models correctly
      labeled the tweets with the appropriate variables between 68.40% and 99.34% of
      the time, and the percentage of maximum possible improvement over a random
      baseline that was achieved by the classification models ranged from 41.59% to
      80.62%. Classifiers with the highest performance scores that also achieved the
      highest percentage of the maximum possible improvement over a random baseline
      were Policy/Government (performance: 0.94; % improvement: 80.62%), Relevance
      (performance: 0.94; % improvement: 75.26%), Ad or Promotion (performance: 0.89; %
      improvement: 72.69%), and Marketing (performance: 0.91; % improvement: 72.56%).
      The most appropriate word-grouping unit (n-gram) was 1 for the majority of
      classifiers. Performance continued to marginally increase with the size of the
      training dataset of manually annotated data, but eventually leveled off. Even at
      low dataset sizes of 4000 observations, performance characteristics were fairly
      sound. CONCLUSIONS: Social media outlets like Twitter can uncover real-time
      snapshots of personal sentiment, knowledge, attitudes, and behavior that are not
      as accessible, at this scale, through any other offline platform. Using the vast
      data available through social media presents an opportunity for social science
      and public health methodologies to utilize computational methodologies to enhance
      and extend research and practice. This study was successful in automating a
      complex five-category manual content analysis of e-cigarette-related content on
      Twitter using machine learning techniques. The study details machine learning
      model specifications that provided the best accuracy for data related to e
      cigarettes, as well as a replicable methodology to allow extension of these
      methods to additional topics.

PMID- 26307514
TI  - Trabeculectomy Versus EX-PRESS Shunt Versus Ahmed Valve Implant: Short-term
      Effects on Corneal Endothelial Cells.
AB  - PURPOSE: To evaluate short-term changes in corneal endothelial cells after
      trabeculectomy, EX-PRESS device implantation, and Ahmed valve implantation for
      the treatment of primary open-angle glaucoma. DESIGN: Prospective,
      interventional, comparative case series with contralateral eye control study.
      METHODS: We prospectively evaluated the changes in number, density, and shape of
      the corneal endothelium cells in 128 eyes of 64 patients divided into 3 groups
      depending on the treatment received. Corneal specular microscopy was performed
      with a noncontact specular microscope preoperatively and at 1 and 3 months after
      surgery. The changes at each time point were compared with those of the control
      group, which consisted of 32 contralateral glaucomatous eyes receiving
      antiglaucoma medications without any previous glaucoma surgery. RESULTS: In the
      subjects who underwent trabeculectomy, corneal endothelial cell density (ECD)
      significantly decreased by 3.5% (P = .012, paired t test) at 1 month and 4.2% (P
      = .007) at 3 months after surgery, compared to the baseline values. In the Ahmed
      valve group ECD did not change at 1 month after surgery and had a significant
      3.5% decrease at 3 months (P = .04). In the patients who underwent EX-PRESS
      implantation and in the control group ECD did not change either at 1 month or at
      3 months after surgery (P > .05). CONCLUSIONS: EX-PRESS shunt, compared to
      trabeculectomy and Ahmed valve, seems to be a safer procedure regarding the risk
      of endothelial cell loss. For this reason, it may be the treatment of choice in
      patients with significant low corneal ECD before surgery or other risk factors
      for corneal damage.

PMID- 26307515
TI  - Protein retention on plasma-treated hierarchical nanoscale gold-silver platform.
AB  - Dense arrays of gold-supported silver nanowires of about 100 nm in diameter grown
      directly in the channels of nanoporous aluminium oxide membrane were fabricated
      and tested as a novel platform for the immobilization and retention of BSA
      proteins in the microbial-protective environments. Additional treatment of the
      silver nanowires using low-temperature plasmas in the inductively-coupled plasma
      reactor and an atmospheric-pressure plasma jet have demonstrated that the
      morphology of the nanowire array can be controlled and the amount of the retained
      protein may be increased due to the plasma effect. A combination of the neutral
      gold sublayer with the antimicrobial properties of silver nanowires could
      significantly enhance the efficiency of the platforms used in various
      biotechnological processes. 

PMID- 26307516
TI  - Chlamydia screening for pregnant women aged 16-25 years attending an antenatal
      service: a cost-effectiveness study.
AB  - OBJECTIVE: Determine the cost-effectiveness of screening all pregnant women aged
      16-25 years for chlamydia compared with selective screening or no screening.
      DESIGN: Cost effectiveness based on a decision model. SETTING: Antenatal clinics
      in Australia. SAMPLE: Pregnant women, aged 16-25 years. METHODS: Using clinical
      data from a previous study, and outcomes data from the literature, we modelled
      the short-term perinatal (12-month time horizon) incremental direct costs and
      outcomes from a government (as the primary third-party funder) perspective for
      chlamydia screening. Costs were derived from the Medicare Benefits Schedule,
      Pharmaceutical Benefits Scheme, and average cost-weights reported for
      hospitalisations classified according to the Australian refined diagnosis-related
      groups. MAIN OUTCOME MEASURES: Direct costs of screening and managing chlamydia
      complications, number of chlamydia cases detected and treated, and the
      incremental cost-effectiveness ratios were estimated and subjected to sensitivity
      analyses. RESULTS: Assuming a chlamydia prevalence rate of 3%, screening all
      antenatal women aged 16-25 years at their first antenatal visit compared with no
      screening was $34,931 per quality-adjusted life-years gained. Screening all women
      could result in cost savings when chlamydia prevalence was higher than 11%. The
      incremental cost-effectiveness ratios were most sensitive to the assumed
      prevalence of chlamydia, the probability of pelvic inflammatory disease, the
      utility weight of a positive chlamydia test and the cost of the chlamydia test
      and doctor's appointment. CONCLUSION: From an Australian government perspective,
      chlamydia screening of all women aged 16-25 years old during one antenatal visit
      was likely to be cost-effective compared with no screening or selective
      screening, especially with increasing chlamydia prevalence. TWEETABLE ABSTRACT:
      Chlamydia screening for all pregnant women aged 16-25 years during an antenatal
      visit is cost effective.

PMID- 26307517
TI  - Plasma carnosine, but not muscle carnosine, attenuates high-fat diet-induced
      metabolic stress.
AB  - There is growing in vivo evidence that the dipeptide carnosine has protective
      effects in metabolic diseases. A critical unanswered question is whether its site
      of action is tissues or plasma. This was investigated using oral carnosine versus
      beta-alanine supplementation in a high-fat diet rat model. Thirty-six male
      Sprague-Dawley rats received a control diet (CON), a high-fat diet (HF; 60% of
      energy from fat), the HF diet with 1.8% carnosine (HFcar), or the HF diet with 1%
      beta-alanine (HFba), as beta-alanine can increase muscle carnosine without
      increasing plasma carnosine. Insulin sensitivity, inflammatory signaling, and
      lipoxidative stress were determined in skeletal muscle and blood. In a pilot
      study, urine was collected. The 3 HF groups were significantly heavier than the
      CON group. Muscle carnosine concentrations increased equally in the HFcar and
      HFba groups, while elevated plasma carnosine levels and carnosine-4-hydroxy-2
      nonenal adducts were detected only in the HFcar group. Elevated plasma and urine
      N(epsilon)-(carboxymethyl)lysine in HF rats was reduced by ~50% in the HFcar
      group but not in the HFba group. Likewise, inducible nitric oxide synthase mRNA
      was decreased by 47% (p < 0.05) in the HFcar group, but not in the HFba group,
      compared with HF rats. We conclude that plasma carnosine, but not muscle
      carnosine, is involved in preventing early-stage lipoxidation in the circulation
      and inflammatory signaling in the muscle of rats. 

PMID- 26307518
TI  - Body composition changes affect energy cost of running during 12 months of
      specific diet and training in amateur athletes.
AB  - Considering the relation between body weight composition and energy cost of
      running, we tested the hypothesis that by modifying body composition by means of
      a combined protocol of specific diet and training, the energy cost of motion (Cr)
      may be reduced. Forty-five healthy and normal-weight subjects were divided into 3
      groups that performed a different treatment: the first group attended a dietary
      protocol (D), the second group participated in a running program (R), and the
      third group followed both the dietary and running protocols (R&D). Each subject
      underwent 3 anthropometric and exercise evaluation tests during 1 year (at entry
      (T0), month 6 (T6), and month 12 (T12)) to assess body composition and Cr
      adjustments. The mean fat mass (FM) values were reduced in R&D from 12.0 +/- 4.0
      to 10.4 +/- 3.0 kg (p < 0.05 T0 vs. T12) and in the D group from 14.2 +/- 5.8 to
      11.6 +/- 4.7 kg (p < 0.05 T0 vs. T12). Conversely, the mean fat free mass values
      increased in R&D (from 56.3 +/- 8.8 to 58.3 +/- 9.8 kg, p < 0.05 T0 vs. T12) and
      in the D group (from 50.6 +/- 13.2 to 52.9 +/- 13.6 kg, p < 0.05 T0 vs. T12). The
      mean Cr values of the 2 groups were significantly modified throughout the 1-year
      protocol (1.48 +/- 0.16 and 1.40 +/- 0.15 kcal.kg(-b).km(-1) in the R&D group at
      T0 and T12, respectively; 1.83 +/- 0.17 and 1.76 +/- 0.23 kcal.kg(-b).km(-1) in D
      group at T0 to T12, respectively). The R&D and D groups that underwent the diet
      protocol had a positive change in body composition during the year (FM/fat free
      mass ratio decline), which determined a Cr reduction. 

PMID- 26307519
TI  - Individual variability in cardiac biomarker release after 30 min of high
      intensity rowing in elite and amateur athletes.
AB  - This study had two objectives: (i) to examine individual variation in the pattern
      of cardiac troponin I (cTnI) and N-terminal pro-brain natriuretic peptide (NT
      proBNP) release in response to high-intensity rowing exercise, and (ii) to
      establish whether individual heterogeneity in biomarker appearance was influenced
      by athletic status (elite vs. amateur). We examined cTnI and NT-proBNP in 18
      elite and 14 amateur rowers before and 5 min, 1, 3, 6, 12, and 24 h after a 30
      min maximal rowing test. Compared with pre-exercise levels, peak postexercise
      cTnI (pre: 0.014 +/- 0.030 MUg.L(-1); peak post: 0.058 +/- 0.091 MUg.L(-1); p =
      0.000) and NT-proBNP (pre: 15 +/- 11 ng.L(-1); peak post: 31 +/- 19 ng.L(-1); p =
      0.000) were elevated. Substantial individual heterogeneity in peak and time
      course data was noted for cTnI. Peak cTnI exceeded the upper reference limit
      (URL) in 9 elite and 3 amateur rowers. No rower exceeded the URL for NT-proBNP.
      Elite rowers had higher baseline (0.019 +/- 0.038 vs. 0.008 +/- 0.015 MUg.L(-1);
      p = 0.003) and peak postexercise cTnI (0.080 +/- 0.115 vs. 0.030 +/- 0.029 MUg.L(
      1); p = 0.022) than amateur rowers, but the change with exercise was similar
      between groups. There were no significant differences in baseline and peak
      postexercise NT-proBNP between groups. In summary, marked individuality in the
      cTnI response to a short but high-intensity rowing bout was observed. Athletic
      status did not seem to affect the change in cardiac biomarkers in response to
      high-intensity exercise. 

PMID- 26307520
TI  - Discussion of "Cardiorespiratory alterations induced by low-intensity exercise
      performed in water or on land".

PMID- 26307521
TI  - Reply to "Discussion: 'Cardiorespiratory alterations induced by low-intensity
      exercise performed in water or on land' - What hemodynamic changes during cycling
      in water?".

PMID- 26307522
TI  - Mechanism of Nickel(II)-Catalyzed Oxidative C(sp2)-H/C(sp3)-H Coupling of
      Benzamides and Toluene Derivatives.
AB  - The Ni-catalyzed C(sp(2))-H/C(sp(3))-H coupling of benzamides with toluene
      derivatives was recently successfully achieved with mild oxidant iC3F7I. Herein,
      we employ density functional theory (DFT) methods to resolve the mechanistic
      controversies. Two previously proposed mechanisms are excluded, and our proposed
      mechanism involving iodine-atom transfer (IAT) between iC3F7I and the Ni(II)
      intermediate was found to be more feasible. With this mechanism, the presence of
      a carbon radical is consistent with the experimental observation that (2,2,6,6
      tetramethylpiperidin-1-yl)oxyl (TEMPO) completely quenches the reaction.
      Meanwhile, the hydrogen-atom abstraction of toluene is irreversible and the
      activation of the C(sp(2))-H bond of benzamides is reversible. Both of these
      conclusions are in good agreement with Chatani's deuterium-labeling experiments.

PMID- 26307524
TI  - Three-fold higher frequency of circulating chronic lymphocytic leukemia-like B
      cell clones in patients with Ph-Myeloproliferative neoplasms.
AB  - Philadelphia chromosome-negative Myeloproliferative neoplasms (Ph-MPN) are
      accompanied by a markedly increased risk for development of chronic lymphocytic
      leukemia (CLL) compared to the general population. However, the pattern of onset
      and the biological characteristics of CLL in patients with coexistent Ph-MPN are
      highly heterogeneous rendering questionable if the above association reflects a
      causal relationship between the two disorders or merely represents a random
      event. By analyzing 82 patients with Ph-MPN and 100 age-matched healthy
      individuals we demonstrate that MPN patients have an almost threefold higher
      prevalence of, typically low-count, CLL-like monoclonal B lymphocytosis (MBL)
      compared to normal adults. The clone size remained unaltered during the disease
      course and unaffected by the administration of hydroxycarbamide, whereas no
      patient with Ph-MPN/MBL progressed to CLL during a median follow up of 4 years.
      Monoclonal B cells in Ph-MPN/MBL patients and normal individuals and in four more
      patients with coexistence of overt CLL and MPN displayed heterogeneous biological
      characteristics, while the JAK2V617F mutation was absent in isolated lymphocytes
      from Ph-MPN patients with coexistence of CLL. Despite its clinical and biological
      variability, the increased incidence of MBL in Ph-MPN patients along with the one
      reported for CLL further enforces the notion of a shared pathophysiology among
      the two malignancies via a common genetic link and/or microenviromental
      interactions.

PMID- 26307523
TI  - Bendamustine in combination with rituximab for elderly patients with previously
      untreated B-cell chronic lymphocytic leukemia: A retrospective analysis of real
      life practice in Italian hematology departments.
AB  - The front-line therapy for CLL young and fit patients is chemo-immunotherapy with
      fludarabine-cyclophosphamide-rituximab (FCR). FCR regimen results in a
      significant myelosuppression and high rates of early and late infections
      especially in elderly patients. German CLL study group compared FCR vs.
      bendamustine-rituximab (BR) in fit untreated patients. The response rates with BR
      or FCR were comparable, BR could be an alternative 1st-line treatment for elderly
      patients. Here we report retrospective data of 70 elderly (>=65 years) CLL
      patients from 12 Italian centers treated with BR as front-line therapy. The
      primary end points were overall response rate (complete remission/partial
      remission) and safety. Forty-seven males and 23 females, with a median age of 72
      years, were included in the study. Eight patients were unfit for CIRS. The OR
      rate was 88.6% (31.4% CR and 57.2% PR). Progression free survival, treatment free
      survival and overall survival rates at 2-years were 79%, 90.3% and 89.6%,
      respectively. Only del17 was independent unfavorable parameter on the response
      rate and PFS. Our results indicate that BR front-line at standard dose provides a
      high response rate with a good safety profile, even if more than 50% of patients
      experienced a bendamustine dose reduction until 70 mg/m2.

PMID- 26307525
TI  - The role of coffee consumption on the 10-year (2004-2014) Acute Coronary Syndrome
      (ACS) incidence among cardiac patients: the GREECS observational study.
AB  - The association between long-term coffee consumption and 10-year cardiovascular
      disease incidence among Acute Coronary Syndrome (ACS) patients was evaluated.
      From 2003 to 2004, 2172 ACS consecutive patients from six major Greek hospitals
      were enrolled. During 2013-2014, the 10-year follow-up was performed (88%
      participation rate) and recurrent fatal or non-fatal ACS was recorded. Baseline
      coffee consumption (cups/day) was assessed using a semi-quantitative Food
      Frequency Questionnaire. Multi adjusted analysis revealed that 1-2 cups of
      coffee/day versus no consumption had an adverse effect on the ACS incidence [odds
      ratio (OR) = 1.35, 95% confidence interval (CI) 1.01, 1.79]. In subgroup
      analysis, with hypertension as strata, only the normotensive reached
      significance. Odds ratios for 1-2 and >=3 cups relative to no consumption were
      [OR = 1.66, 95% CI 1.07, 2.60] and [OR = 1.86, 95% CI 1.06, 3.27], respectively,
      after controlling for potential confounders. Thus, avoidance of coffee may be of
      high importance to ameliorate disease prognosis among cardiac patients. 

PMID- 26307526
TI  - Effects of Combined Electrical Stimulation of the Dorsal Column and Dorsal Roots
      on Wide-Dynamic-Range Neuronal Activity in Nerve-Injured Rats.
AB  - OBJECTIVES: Electrical stimulation at the dorsal column (DC) and dorsal root (DR)
      may inhibit spinal wide-dynamic-range (WDR) neuronal activity in nerve-injured
      rats. The objective of this study was to determine if applying electrical
      conditioning stimulation (CS) at both sites provides additive or synergistic
      benefits. MATERIALS AND METHODS: By conducting in vivo extracellular recordings
      of WDR neurons in rats that had undergone L5 spinal nerve ligation, we tested
      whether combining 50 Hz CS at the two sites in either a concurrent (2.5 min) or
      alternate (5 min) pattern inhibits WDR neuronal activity better than CS at DC
      alone (5 min). The intensities of CS were determined by recording antidromic
      compound action potentials to graded stimulation at the DC and DR. We measured
      the current thresholds that resulted in the first detectable Aalpha/beta waveform
      (Ab0) and the peak Aalpha/beta waveform (Ab1) to select CS intensity at each
      site. The same number of electrical pulses and amount of current were delivered
      in different patterns to allow comparison. RESULTS: At a moderate intensity of
      50% (Ab0 + Ab1), different patterns of CS all attenuated the C-component of WDR
      neurons in response to graded intracutaneous electrical stimuli (0.1-10 mA, 2
      msec) and inhibited windup in response to repetitive noxious stimuli (0.5 Hz).
      However, the inhibitory effects did not differ significantly between different
      patterns. At the lower intensity (Ab0), no CS inhibited WDR neurons. CONCLUSIONS:
      These findings suggest that combined stimulation of DC and DR may not be superior
      to DC stimulation alone for inhibition of WDR neurons.

PMID- 26307527
TI  - PMCA activity and membrane tubulin affect deformability of erythrocytes from
      normal and hypertensive human subjects.
AB  - Our previous studies demonstrated formation of a complex between acetylated
      tubulin and brain plasma membrane Ca(2+)-ATPase (PMCA), and the effect of the
      lipid environment on structure of this complex and on PMCA activity.
      Deformability of erythrocytes from hypertensive human subjects was reduced by an
      increase in membrane tubulin content. In the present study, we examined the
      regulation of PMCA activity by tubulin in normotensive and hypertensive
      erythrocytes, and the effect of exogenously added diacylglycerol (DAG) and
      phosphatidic acid (PA) on erythrocyte deformability. Some of the key findings
      were that: (i) PMCA was associated with tubulin in normotensive and hypertensive
      erythrocytes, (ii) PMCA enzyme activity was directly correlated with erythrocyte
      deformability, and (iii) when tubulin was present in the erythrocyte membrane,
      treatment with DAG or PA led to increased deformability and associated PMCA
      activity. Taken together, our findings indicate that PMCA activity is involved in
      deformability of both normotensive and hypertensive erythrocytes. This
      rheological property of erythrocytes is affected by acetylated tubulin and its
      lipid environment because both regulate PMCA activity. 

PMID- 26307528
TI  - On the translocation of botulinum and tetanus neurotoxins across the membrane of
      acidic intracellular compartments.
AB  - Tetanus and botulinum neurotoxins are produced by anaerobic bacteria of the genus
      Clostridium and are the most poisonous toxins known, with 50% mouse lethal dose
      comprised within the range of 0.1-few nanograms per Kg, depending on the
      individual toxin. Botulinum neurotoxins are similarly toxic to humans and can
      therefore be considered for potential use in bioterrorism. At the same time,
      their neurospecificity and reversibility of action make them excellent
      therapeutics for a growing and heterogeneous number of human diseases that are
      characterized by a hyperactivity of peripheral nerve terminals. The complete
      crystallographic structure is available for some botulinum toxins, and reveals
      that they consist of four domains functionally related to the four steps of their
      mechanism of neuron intoxication: 1) binding to specific receptors of the
      presynaptic membrane; 2) internalization via endocytic vesicles; 3) translocation
      across the membrane of endocytic vesicles into the neuronal cytosol; 4) catalytic
      activity of the enzymatic moiety directed towards the SNARE proteins. Despite the
      many advances in understanding the structure-mechanism relationship of tetanus
      and botulinum neurotoxins, the molecular events involved in the translocation
      step have been only partially elucidated. Here we will review recent advances
      that have provided relevant insights on the process and discuss possible models
      that can be experimentally tested. This article is part of a Special Issue
      entitled: Pore-Forming Toxins edited by Mauro Dalla Serra and Franco Gambale. 

PMID- 26307529
TI  - Edge state magnetism in zigzag-interfaced graphene via spin susceptibility
      measurements.
AB  - Development of graphene spintronic devices relies on transforming it into a
      material with a spin order. Attempts to make graphene magnetic by introducing
      zigzag edge states have failed due to energetically unstable structure of torn
      zigzag edges. Here, we report on the formation of nanoridges, i.e., stable
      crystallographically oriented fluorine monoatomic chains, and provide
      experimental evidence for strongly coupled magnetic states at the graphene
      fluorographene interfaces. From the first principle calculations, the spins at
      the localized edge states are ferromagnetically ordered within each of the zigzag
      interface whereas the spin interaction across a nanoridge is antiferromagnetic.
      Magnetic susceptibility data agree with this physical picture and exhibit
      behaviour typical of quantum spin-ladder system with ferromagnetic legs and
      antiferromagnetic rungs. The exchange coupling constant along the rungs is
      measured to be 450 K. The coupling is strong enough to consider graphene with
      fluorine nanoridges as a candidate for a room temperature spintronics material. 

PMID- 26307530
TI  - Disease disclosure, treatment adherence, and behavioural profile in a cohort of
      vertically acquired HIV-infected adolescents. NeuroCoRISpeS study.
AB  - Advances in care and antiretroviral treatment, improved life expectancy and
      quality of life in children with perinatally-acquired human immunodeficiency
      virus (HIV) infection. There is increasing interest in the chronic effects of
      growing up with HIV. The aim of this study was to assess the psychosocial,
      emotional and behavioural functioning in a cohort of perinatally-acquired HIV
      infected adolescents. Data were obtained through semi-structured interviews and
      the Strengths and Difficulties Questionnaire (SDQ) for emotional and behavioural
      disorders screening. RESULTS: A total of 95 patients (58% women) were assessed
      with a median age of 15 years (11-19.1) and a median age at diagnosis of 1.7
      years (0-12.2). The median CD4 count, at the inclusion, was 626 cells/mm(3) (132
      998), with 34% (10-52%). Viral load was <50 copies/ml in 72% of patients. Eighty
      one per cent knew their diagnosis and optimal adherence was achieved in 53%.
      Passive coping was reported in 58.4% of the adolescents. Only 7.7% of teenagers
      had a complete and adequate knowledge of their disease and only 18.2% had shared
      it with their friends. Six unwanted pregnancies occurred (11% of women). Most of
      them (90%) attended school but 60% had been held back one or more school years.
      Overall, SDQ scored a risk of behavioural and emotional problems in 24.5%. The
      report of behaviours associated with hyperactivity was high in 14.9% of the
      population and borderline in 18.1%. Adolescents with encephalopathy accounted for
      44% of those whose total scores fell in either the abnormal and borderline ranges
      for emotional difficulties (p = .038). CONCLUSION: Perinatally-acquired HIV
      infected adolescents showed significant psychosocial and behavioural health risks
      that should bring attention to prevention and health care programmes. An earlier
      disclosure to children could favour a better psychological adjustment and a
      better treatment adherence. Future studies are needed to assess the relationship
      between vertically acquired HIV-infection and hyperactivity.

PMID- 26307531
TI  - Intramuscular phosphagen status and the relationship to muscle performance across
      the age spectrum.
AB  - PURPOSE: To examine age-related differences in intramuscular concentrations of
      adenosine triphosphate (ATP), free creatine (FCr), phosphocreatine (PCr) and
      total creatine (TCr) and if these differences were related to muscle performance.
      METHODS: Forty-two healthy, non-sedentary, males between 20 and 76 years provided
      muscle samples to determine [ATP], [FCr], [PCr], and [TCr]. Maximal strength and
      endurance were assessed and correlated with intramuscular variables. RESULTS:
      Intramuscular [ATP] decreased by 13.5% (p = 0.013) in the older cohort (18.0 +/-
      0.6 mmol/kg dry wt) vs. the young cohort (20.8 +/- 0.9 mmol/kg dry wt) and was
      significantly correlated to age (r = -0.38, p = 0.008). No other differences were
      observed between age groups for intramuscular [PCr], [FCr], [TCr], or [PCr]:[TCr]
      (p > 0.05). The older cohort consumed significantly less (p < 0.05) dietary
      protein when compared to the young cohort. Bivariate correlations were found for
      intramuscular [ATP] and lower body 1RM (r = 0.24, p = 0.066), leg press volume
      and free creatine (r = 0.325, p = 0.036) and leg press repetitions and free
      creatine (r = 0.373, p = 0.015). Partial correlations controlling for age
      eliminated the relationship between [ATP] and 1RM while intramuscular free
      creatine and leg press repetitions remained significant (p < 0.05) and leg press
      volume approached significance (p = 0.095). CONCLUSION: These results expand upon
      previous observations indicative of age-related reductions in intramuscular [ATP]
      and dietary protein intake. The lack of change in other intramuscular PCr system
      markers are suggestive of dysfunctions at the mitochondrial level while the
      impact of neuromuscular changes, lean mass cross-sectional area and differences
      in physical activity are also important.

PMID- 26307532
TI  - Unaccompanied refugee minors' early life narratives of physical abuse from
      caregivers and teachers in their home countries.
AB  - The early life narratives of 34 unaccompanied refugee minors, especially their
      reports of interpersonal violence, were analyzed using Interpretative
      Phenomenological Analysis (IPA). The youth originated from eight countries, with
      Afghanistan, Eritrea, and Sri Lanka being the most frequent origins, and they
      arrived to Norway before the age of 15. Four of these youth were girls. The
      physical violence took place at home and/or at school and could be extremely
      harsh. Approximately half of the youth expressed some type of ambivalence toward
      the perpetrator. In analyzing how the youth understood the reasons for violence
      two categories of internal and three categories of external attributions were
      found. Several of the youth blamed their own behavior for the abuse, although
      such internal attributions were frequently combined with external attributions.
      Some different patterns of attributions emerged between home and school violence.
      Most of the youth placed the blame for school violence on their own behavior or
      that violence was part of normal school discipline. For violence at home there
      was a tendency to place more blame on the perpetrator (mostly fathers). Possible
      long-term consequences of the experiences and the different attributional styles
      as well as implications of the findings are discussed. Professionals should
      assess refugee children for interpersonal violence experiences as well as for
      other experiences in their home country. 

PMID- 26307533
TI  - Popular Glucose Tracking Apps and Use of mHealth by Latinos With Diabetes:
      Review.
AB  - BACKGROUND: Diabetes mellitus in the United States is an increasingly common
      chronic disease, costing hundreds of billions of dollars and contributing to
      hundreds of thousands of deaths each year. The prevalence of diabetes is over 50%
      higher in Latinos than in the general population, and this group also suffers
      from higher rates of complications and diabetes-related mortality than NHWs.
      mHealth is a promising new treatment modality for diabetes, though few smartphone
      apps have been designed specifically for Latinos. OBJECTIVE: The objectives of
      our study were: (1) to identify the most common features of the most popular
      diabetes apps and consider how such features may be improved to meet the needs of
      Latinos; (2) to determine the use of diabetes apps among a sample of online
      Hispanics in the US. METHODS: Our study consisted of two parts. First, 20 of the
      most popular diabetes apps were reviewed in order to ascertain the most prevalent
      features and functionalities. Second, an online survey was fielded through a
      popular health website for Latinos (HolaDoctor) inquiring about respondents' use
      of diabetes apps. RESULTS: Approximately one-third of apps reviewed were
      available in Spanish. The most common features were blood glucose
      recording/annotation and activity logs. The majority of apps permitted
      exportation of data via e-mail but only a third enabled uploading to an online
      account. Twenty percent of apps reviewed could connect directly with a
      glucometer, and 30% had reminder functionalities prompting patients to take
      medications or check blood glucose levels. Over 1600 online surveys were
      completed during the second half of April 2014. More than 90% of respondents were
      from the United States, including Puerto Rico. The majority of respondents used a
      device running on an Android platform while only a quarter used an iPhone. Use of
      diabetes apps was approximately 3% among diabetic respondents and 3.6% among
      diabetic respondents who also had a smartphone. Among app users, blood glucose
      and medication diaries were the most frequently used functionalities while
      hemoglobin A1c and insulin diaries were the least used. A significant majority of
      app users did not share their progress on social media though many of these were
      willing to share it with their doctor. CONCLUSIONS: Latino diabetics have unique
      needs and this should be reflected in diabetes apps designed for this population.
      Existing research as well as our survey results suggest that many Latinos do not
      possess the prerequisite diabetes knowledge or self-awareness to fully benefit
      from the most prevalent functionalities offered by the most popular diabetes
      apps. We recommend developers incorporate more basic features such as diabetes
      education, reminders to check blood glucose levels or take medications, Spanish
      language interfaces, and glucometer connectivities, which are relatively
      underrepresented in the most popular diabetes apps currently available in
      Spanish.

PMID- 26307534
TI  - Free hemoglobin increases von Willebrand factor-mediated platelet adhesion in
      vitro: implications for circulatory devices.
AB  - Intravascular hemolysis occurs in patients on extracorporeal membrane
      oxygenation. High levels of free acellular adult hemoglobin (free HbA) are
      associated with clotting in this mechanical device that can result in thrombotic
      complications. Adsorption of fibrinogen onto the surface of biomaterial
      correlates with platelet adhesion, which is mediated by von Willebrand factor
      (VWF). Because free Hb interacts with VWF, we studied the effect of hemoglobin
      (Hb) on platelet adhesion to fibrin(ogen) under conditions of different
      hydrodynamic forces. This effect was investigated using purified human HbA and
      fibrinogen, extracellular matrix, collagen, or purified plasma VWF as surface
      coated substrates to examine flow-dependent platelet adhesion. Antibodies and VWF
      deficient plasma were also used. Free Hb (>=50 mg/dL) effectively augmented
      platelet adhesion, and microthrombi formation on fibrin(ogen), extracellular
      matrix, and collagen at high shear stress. The effect of free Hb was effectively
      blocked by anti-glycoprotein Ibalpha (GPIbalpha) antibodies or depletion of VWF.
      Unexpectedly, free Hb also promoted firm platelet adhesion and stable
      microthrombi on VWF. Lastly, we determined that Hb interacts directly with the A1
      domain. This study is the first to demonstrate that extracellular Hb directly
      affects the GPIbalpha-VWF interaction in thrombosis, and describes another
      mechanism by which hemolysis is connected to thrombotic events.

PMID- 26307536
TI  - Regulation of mitochondrial morphology and cell cycle by microRNA-214 targeting
      Mitofusin2.
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disease
      caused by the increase in CAG repeats beyond 36 at the exon1 of the gene
      Huntingtin (HTT). Among the various dysfunctions of biological processes in HD,
      transcription deregulation due to abnormalities in actions of transcription
      factors has been considered to be one of the important pathological conditions.
      In addition, deregulation of microRNA (miRNA) expression has been described in
      HD. Earlier, expression of microRNA-214 (miR-214) has been shown to increase in
      HD cell models and target HTT gene; the expression of the later being inversely
      correlated to that of miR-214. In the present communication, we observed that the
      expressions of several HTT co-expressed genes are modulated by exogenous
      expression of miR-214 or by its mutant. Among several HTT co-expressed genes,
      MFN2 was shown to be the direct target of miR-214. Exogenous expression of miR
      214, repressed the expression of MFN2, increased the distribution of fragmented
      mitochondria and altered the distribution of cells in different phases of cell
      cycle. In summary, we have shown that increased expression of miR-214 observed in
      HD cell model could target MFN2, altered mitochondrial morphology and deregulated
      cell cycle. Inhibition of miR-214 could be a possible target of intervention in
      HD pathogenesis.

PMID- 26307535
TI  - Cell of origin of transformed follicular lymphoma.
AB  - Follicular lymphoma (FL) is an indolent disease but transforms in 2% to 3% of
      patients per year into aggressive, large cell lymphoma, a critical event in the
      course of the disease associated with increased lymphoma-related mortality. Early
      transformation cannot be accurately predicted at the time of FL diagnosis and the
      biology of transformed FL (TFL) is poorly understood. Here, we assembled a cohort
      of 126 diagnostic FL specimens including 40 patients experiencing transformation
      (<5 years) and 86 patients not experiencing transformation for at least 5 years.
      In addition, we assembled an overlapping cohort of 155 TFL patients, including
      114 cases for which paired samples were available, and assessed temporal changes
      of routinely available biomarkers, outcome after transformation, as well as
      molecular subtypes of TFL. We report that the expression of IRF4 is an
      independent predictor of early transformation (Hazard ratio, 13.3; P < .001). We
      also show that composite histology at the time of transformation predicts
      favorable prognosis. Moreover, applying the Lymph2Cx digital gene expression
      assay for diffuse large B-cell lymphoma (DLBCL) cell-of-origin determination to
      110 patients with DLBCL-like TFL, we demonstrate that TFL is of the germinal
      center B-cell-like subtype in the majority of cases (80%) but that a significant
      proportion of cases is of the activated B-cell-like (ABC) subtype (16%). These
      latter cases are commonly negative for BCL2 translocation and arise
      preferentially from BCL2 translocation-negative and/or IRF4-expressing FLs. Our
      study demonstrates the existence of molecular heterogeneity in TFL as well as its
      relationship to the antecedent FL. 

PMID- 26307537
TI  - C-type natriuretic peptide signalling drives homeostatic effects in human
      chondrocytes.
AB  - Signals induced by mechanical loading and C-type natriuretic peptide (CNP)
      represent chondroprotective routes that may potentially prevent osteoarthritis
      (OA). We examined whether CNP will reduce hyaluronan production and export via
      members of the multidrug resistance protein (MRP) and diminish pro-inflammatory
      effects in human chondrocytes. The presence of interleukin-1beta (IL-1beta)
      increased HA production and export via MRP5 that was reduced with CNP and/or
      loading. Treatment with IL-1beta conditioned medium increased production of
      catabolic mediators and the response was reduced with the hyaluronan inhibitor,
      Pep-1. The induction of pro-inflammatory cytokines by the conditioned medium was
      reduced by CNP and/or Pep-1, alphaCD44 or alphaTLR4 in a cytokine-dependent
      manner, suggesting that the CNP pathway is protective and should be exploited
      further.

PMID- 26307539
TI  - Caregiver coaching program effect: Reducing heart failure patient
      rehospitalizations and improving caregiver outcomes among African Americans.
AB  - OBJECTIVES: (1) Test whether FamHFcare intervention could reduce patients' heart
      failure (HF)-related rehospitalizations and improve family caregiver outcomes;
      (2) calculate effect size on caregiver outcomes; and (3) evaluate the FamHFcare.
      BACKGROUND: Few interventions target family caregivers for HF home care. METHODS:
      This study was a mixed method design with stratification and random assignment of
      20 African American HF patient/caregiver dyads. Descriptive, univariate
      parametric/non-parametric, and post-hoc analyses were used. RESULTS: At 6 months,
      compared to standard care, the intervention group had significantly fewer HF
      rehospitalizations (M-W z = -1.8, p = 0.03), while caregiver confidence (M-W z =
      2.8, p = 0.003) and social support scores (M-W z = 2.4, p = 0.01) were
      significantly higher, and caregiver depression (M-W z = -2.4, p = 0.01) were
      significantly lower. Caregivers rated the FamHFcare as helpful (M = 46.8 +/-
      4.1). CONCLUSIONS: The FamHFcare intervention was associated with fewer HF
      patient rehospitalizations and improved caregiver outcomes.

PMID- 26307538
TI  - Neural stem/progenitor cell properties of glial cells in the adult mouse auditory
      nerve.
AB  - The auditory nerve is the primary conveyor of hearing information from sensory
      hair cells to the brain. It has been believed that loss of the auditory nerve is
      irreversible in the adult mammalian ear, resulting in sensorineural hearing loss.
      We examined the regenerative potential of the auditory nerve in a mouse model of
      auditory neuropathy. Following neuronal degeneration, quiescent glial cells
      converted to an activated state showing a decrease in nuclear chromatin
      condensation, altered histone deacetylase expression and up-regulation of
      numerous genes associated with neurogenesis or development. Neurosphere formation
      assays showed that adult auditory nerves contain neural stem/progenitor cells
      (NSPs) that were within a Sox2-positive glial population. Production of
      neurospheres from auditory nerve cells was stimulated by acute neuronal injury
      and hypoxic conditioning. These results demonstrate that a subset of glial cells
      in the adult auditory nerve exhibit several characteristics of NSPs and are
      therefore potential targets for promoting auditory nerve regeneration. 

PMID- 26307540
TI  - Is it necessary to cover the macular hole with the inverted internal limiting
      membrane flap in macular hole surgery? A case report.
AB  - BACKGROUND: To report a case of late closure of idiopathic full-thickness macular
      hole (FTMH) after vitrectomy with the inverted internal limiting membrane (ILM)
      technique. CASE PRESENTATION: A 68-year-old lady with a stage IV FTMH underwent
      pars plana vitrectomy with 25 gauge plus transconjunctival system, ILM peeling
      and gas tamponade. The inverted ILM flap technique was adopted, except that no
      extra surgical manipulation was used to cover the macular hole with the ILM flap.
      Surgical outcome was monitored with serial optical coherence tomography (OCT).
      Complete closure of the FTMH with resolution of intraretinal cystic changes was
      confirmed on OCT at 16 months postoperatively. Visual acuity improved from a
      baseline level of 0.1 to 0.4. CONCLUSION: Idiopathic macular hole closure could
      be delayed to beyond 1 year following the inverted ILM flap technique, especially
      if the macular hole was not covered with the ILM flap. Not all macular holes that
      fail to close in the early postoperative period need to be re-operated and there
      may be no risk of further visual deterioration.

PMID- 26307541
TI  - A Festschrift in honor of David J. Triggle.

PMID- 26307543
TI  - Sandcastle: software for revealing latent information in multiple experimental
      ChIP-chip datasets via a novel normalisation procedure.
AB  - ChIP-chip is a microarray based technology for determining the genomic locations
      of chromatin bound factors of interest, such as proteins. Standard ChIP-chip
      analyses employ peak detection methodologies to generate lists of genomic binding
      sites. No previously published method exists to enable comparative analyses of
      enrichment levels derived from datasets examining different experimental
      conditions. This restricts the use of the technology to binary comparisons of
      presence or absence of features between datasets. Here we present the R package
      Sandcastle - Software for the Analysis and Normalisation of Data from ChIP-chip
      AssayS of Two or more Linked Experiments - which allows for comparative analyses
      of data from multiple experiments by normalising all datasets to a common
      background. Relative changes in binding levels between experimental datasets can
      thus be determined, enabling the extraction of latent information from ChIP-chip
      experiments. Novel enrichment detection and peak calling algorithms are also
      presented, with a range of graphical tools, which facilitate these analyses. The
      software and documentation are available for download from
      http://reedlab.cardiff.ac.uk/sandcastle.

PMID- 26307542
TI  - Rhizobacterial volatiles and photosynthesis-related signals coordinate MYB72
      expression in Arabidopsis roots during onset of induced systemic resistance and
      iron-deficiency responses.
AB  - In Arabidopsis roots, the transcription factor MYB72 plays a dual role in the
      onset of rhizobacteria-induced systemic resistance (ISR) and plant survival under
      conditions of limited iron availability. Previously, it was shown that MYB72
      coordinates the expression of a gene module that promotes synthesis and excretion
      of iron-mobilizing phenolic compounds in the rhizosphere, a process that is
      involved in both iron acquisition and ISR signaling. Here, we show that volatile
      organic compounds (VOCs) from ISR-inducing Pseudomonas bacteria are important
      elicitors of MYB72. In response to VOC treatment, MYB72 is co-expressed with the
      iron uptake-related genes FERRIC REDUCTION OXIDASE 2 (FRO2) and IRON-REGULATED
      TRANSPORTER 1 (IRT1) in a manner that is dependent on FER-LIKE IRON DEFICIENCY
      TRANSCRIPTION FACTOR (FIT), indicating that MYB72 is an intrinsic part of the
      plant's iron-acquisition response that is typically activated upon iron
      starvation. However, VOC-induced MYB72 expression is activated independently of
      iron availability in the root vicinity. Moreover, rhizobacterial VOC-mediated
      induction of MYB72 requires photosynthesis-related signals, while iron deficiency
      in the rhizosphere activates MYB72 in the absence of shoot-derived signals.
      Together, these results show that the ISR- and iron acquisition-related
      transcription factor MYB72 in Arabidopsis roots is activated by rhizobacterial
      volatiles and photosynthesis-related signals, and enhances the iron-acquisition
      capacity of roots independently of the iron availability in the rhizosphere. This
      work highlights the role of MYB72 in plant processes by which root microbiota
      simultaneously stimulate systemic immunity and activate the iron-uptake machinery
      in their host plants. 

PMID- 26307544
TI  - The ellagitannin colonic metabolite urolithin D selectively inhibits EphA2
      phosphorylation in prostate cancer cells.
AB  - SCOPE: The Eph-ephrin system comprises emerging proteins involved in many
      pathophysiological processes. The pharmacological activity of the main
      metabolites derived from the intake of some classes of (poly)phenolic compounds,
      such as caffeoylquinic acids, flavan-3-ols, and ellagitannins, on the Eph-ephrin
      interaction was evaluated at physiological concentrations. Functional studies to
      elucidate their role in prostate cancer were also performed. METHODS AND RESULTS:
      Among the 21 phenolics screened by an ELISA-binding assay, just urolithin C,
      urolithin D, and ellagic acid succeeded to inhibit the EphA2-ephrin-A1 binding.
      Urolithin D, the most active, was a competitive and reversible antagonist of EphA
      receptors able to discriminate between EphA and EphB receptors, showing intra
      classes selectivity. Molecular modeling and structure-activity relationships shed
      light on the binding mode and selective activity of urolithin D. This catabolite
      blocked EphA2 phosphorylation mediated by ephrin-A1, while lacking cytotoxicity
      and anti-proliferative effects, and was inactive on the EphA2 kinase assay.
      CONCLUSION: The mechanisms behind the cancer preventive properties of foods rich
      in flavan-3-ols and caffeoylquinic acids are not associated with metabolic
      pathways directly linked to the Eph-ephrin system. However, the ellagitannin
      derived colonic metabolite urolithin D was able to exert remarkable and selective
      EphA-ephrin-A inhibition, which might impact on prostate cancer prevention.

PMID- 26307545
TI  - Ceruminous adenoma (ceruminoma) arising in a nevus sebaceus of Jadassohn within
      the external auditory canal of a 3 year-old boy - A case report.
AB  - Nevus sebaceus of Jadassohn is a congenital yellowish hairless skin lesion,
      mainly located on the head and neck. A common phenomenon is the coexistence of
      secondary tumors within the lesion. These are mainly benign tumors, the majority
      of which are trichoblastoma and syringocystadenoma papilliferum. A ceruminoma is
      a very rare tumor of the ceruminous glands located in the outer third of the
      auditory canal. It occurs almost exclusively in adults. We describe the case of a
      3-year old boy diagnosed with ceruminous adenoma (ceruminoma) growing within a
      nevus sebaceus of Jadassohn. 

PMID- 26307546
TI  - Role of autophagy in cisplatin-induced ototoxicity.
AB  - OBJECTIVE: Hearing loss is a major side effect of cisplatin chemotherapy.
      Although cell death in cisplatin-induced ototoxicity is primarily caused by
      apoptosis, the exact mechanism behind the ototoxic effects of cisplatin is not
      fully understood. Autophagy is generally known as a pro-survival mechanism that
      protects cells under starvation or stress conditions. However, recent research
      has reported that autophagy plays a functional role in cell death also. This
      study aimed to investigate the role of autophagy in cisplatin-induced ototoxicity
      in an auditory cell line. METHODS: Cultured HEI-OC1 cells were exposed to 30 MUM
      cisplatin for 48 h, and cell viability was tested using MTT assays. To evaluate
      whether autophagy serves to cell death after cisplatin exposure, western blotting
      and immunofluorescence staining for LC3-II were performed. Markers of two
      autophagy-related pathways, mTOR and class III PI3K, were also investigated.
      RESULTS: The formation of the autophagic protein LC3-II in response to 30 MUM
      cisplatin increased with time. The early upregulation of autophagy exerted
      cytoprotective activity via the class III PI3K pathway. But later increase in
      autophagy induced cell death by suppressing the mTOR pathway. CONCLUSION: Our
      results prove that autophagy could induce cell death during cisplatin-induced
      ototoxicity, and modulating the autophagic pathway might be another strategy
      against cisplatin-induced ototoxicity.

PMID- 26307547
TI  - Potential mechanisms regulating pulmonary pathology in inflammatory bowel
      disease.
AB  - Inflammatory bowel disease is associated with a number of comorbidities that
      arise at extraintestinal sites, including the lung. Pulmonary manifestations
      reported in inflammatory bowel disease include bronchiectasis, chronic bronchitis
      and importantly, a range of subclinical respiratory abnormalities that are often
      overlooked in routine clinical evaluation. Whereas evidence for the pulmonary
      manifestations of Inflammatory bowel disease is increasing, little is known about
      the immunologic and physiologic mechanisms regulating cross-talk between the gut
      and lung during disease. This review examines reported lung involvement in
      Inflammatory bowel disease and discusses the possible immune pathways that
      underlie pulmonary pathologies. These mechanisms include dysfunctional immune
      cell homing, systemic inflammation, and microbial dysbiosis; all of which may
      contribute to Inflammatory bowel disease-induced pulmonary inflammation. These
      mechanisms are discussed in the context of our current knowledge of the shared
      mucosal immune system and the immunology of Inflammatory bowel disease. 

PMID- 26307548
TI  - Interplay between HIV-1 and Toll-like receptors in human myeloid cells: friend or
      foe in HIV-1 pathogenesis?
AB  - The Toll-like receptors are the first line of the host response to pathogens,
      representing an essential component of the innate and adaptive immune response.
      They recognize different pathogens and trigger responses directed at eliminating
      the invader and at developing immunologic long-term memory, ultimately affecting
      viral pathogenesis. In viral infections, sensing of nucleic acids and/or viral
      structural proteins generally induces a protective immune response. Thus, it is
      not surprising that many viruses have developed strategies to evade or counteract
      signaling through the Toll-like receptor pathways, to survive the host defense
      machinery and ensure propagation. Thus, Toll-like receptor engagement can also be
      part of viral pathogenic mechanisms. Evidence for a direct interaction of Toll
      like receptors with human immunodeficiency virus type 1 (HIV-1) structures has
      started to be achieved, and alterations of their expression and function have
      been described in HIV-1-positive subjects. Furthermore, Toll-like receptor
      triggering by bacterial and viral ligands have been described to modulate HIV-1
      replication and host response, leading to protective or detrimental effects. This
      review covers major advances in the field of HIV-1 interplay with Toll-like
      receptors, focusing on human myeloid cells (e.g., monocytes/macrophages and
      dendritic cells). The role of this interaction in the dysregulation of myeloid
      cell function and in dictating aspects of the multifaceted pathogenesis of
      acquired immunodeficiency syndrome will be discussed. 

PMID- 26307550
TI  - Crowdsourced 'R&D' and medical research.
AB  - INTRODUCTION OR BACKGROUND: Crowdsourced R&D, a research methodology increasingly
      applied to medical research, has properties well suited to large-scale medical
      data collection and analysis, as well as enabling rapid research responses to
      crises such as disease outbreaks. SOURCES OF DATA: Multidisciplinary literature
      offers diverse perspectives of crowdsourced R&D as a useful large-scale medical
      data collection and research problem-solving methodology. AREAS OF AGREEMENT:
      Crowdsourced R&D has demonstrated 'proof of concept' in a host of different
      biomedical research applications. AREAS OF CONTROVERSY: A wide range of quality
      and ethical issues relate to crowdsourced R&D. GROWING POINTS: The rapid growth
      in applications of crowdsourced R&D in medical research is predicted by an
      increasing body of multidisciplinary theory. AREAS FOR TIMELY RESEARCH: Further
      research in areas such as artificial intelligence may allow better coordination
      and management of the high volumes of medical data and problem-solving inputs
      generated by the crowdsourced R&D process.

PMID- 26307549
TI  - Perforin-2/Mpeg1 and other pore-forming proteins throughout evolution.
AB  - Development of the ancient innate immune system required not only a mechanism to
      recognize foreign organisms from self but also to destroy them. Pore-forming
      proteins containing the membrane attack complex Perforin domain were one of the
      first triumphs of an innate immune system needing to eliminate microbes and
      virally infected cells. Membrane attack complex of complement and Perforin domain
      proteins is unique from other immune effector molecules in that the mechanism of
      attack is strictly physical and unspecific. The large water-filled holes created
      by membrane attack complex of complement and Perforin domain pore formation allow
      access for additional effectors to complete the destruction of the foreign
      organism via chemical or enzymatic attack. Perforin-2/macrophage-expressed
      protein 1 is one of the oldest membrane attack complexes of complement and
      Perforin domain protein involved in immune defense, and it is still functional
      today in vertebrates. Here, we trace the impact of Perforin-2/macrophage
      expressed protein 1 from the earliest multicellular organisms to modern
      vertebrates, as well as review the development of other membrane attack complexes
      of complement and Perforin domain member proteins. 

PMID- 26307552
TI  - Semiconductor Nanowire Light-Emitting Diodes Grown on Metal: A Direction Toward
      Large-Scale Fabrication of Nanowire Devices.
AB  - Bottom-up nanowires are attractive for realizing semiconductor devices with
      extreme heterostructures because strain relaxation through the nanowire sidewalls
      allows the combination of highly lattice mismatched materials without creating
      dislocations. The resulting nanowires are used to fabricate light-emitting diodes
      (LEDs), lasers, solar cells, and sensors. However, expensive single crystalline
      substrates are commonly used as substrates for nanowire heterostructures as well
      as for epitaxial devices, which limits the manufacturability of nanowire devices.
      Here, nanowire LEDs directly grown and electrically integrated on metal are
      demonstrated. Optical and structural measurements reveal high-quality, vertically
      aligned GaN nanowires on molybdenum and titanium films. Transmission electron
      microscopy confirms the composition variation in the polarization-graded AlGaN
      nanowire LEDs. Blue to green electroluminescence is observed from InGaN quantum
      well active regions, while GaN active regions exhibit ultraviolet emission. These
      results demonstrate a pathway for large-scale fabrication of solid state lighting
      and optoelectronics on metal foils or sheets. 

PMID- 26307553
TI  - An investigation of light and sound levels on intensive care units in China.
AB  - BACKGROUND: The intensive care units' (ICU) environment is considered clinically
      relevant sources of stress for patients. OBJECTIVES: To measure 24-h sound and
      light levels in 7 ICUs in China [four medical (MICU), two surgical (SICU) and one
      coronary (CCU) ICUs] and to identify the main sources related to increased sound
      levels. METHODS: Sound pressure and light levels were monitored for specific
      times over a 24-h period using a digital sound level meter and a light detector
      in 7 ICUs. Sound pressure levels were measured for 20min every hour. The main
      events at the time of peak noise levels were recorded. Light levels were measured
      every 2h at three locations for each ICU: near a window, in the centre of the
      room, at eye level of a patient receiving assisted ventilation. RESULTS: The mean
      value of 24-h sound pressure levels exceeded 50dB(A) in all ICUs, ranging from
      56.5 to 70.1dB(A). The SICUs and CCU had higher sound pressure readings from
      0700h to 1600h, compared to the MICUs where the sound pressure readings reflected
      less variability across the 24-h period. Marked differences were observed in
      luminance levels among various ICUs and also across the 24-h period for all three
      locations. The mean highest level of nocturnal luminance at eye level of patients
      receiving assisted ventilation ranged from 15 to 489lx before midnight (1800
      2400h) and 10 to 239lx after midnight (2401-0759h). CONCLUSIONS: High sound
      pressure levels are prevalent throughout 24h in the ICUs, especially in the SICU.
      Many of the readings exceeded international standards. Peak sound pressure levels
      were related primarily to staff activities and the alarm sounds of machines. ICU
      patients are exposed to high levels of artificial light continuously throughout
      the day and night.

PMID- 26307551
TI  - A distinct three-helix centipede toxin SSD609 inhibits I(ks) channels by
      interacting with the KCNE1 auxiliary subunit.
AB  - KCNE1 is a single-span transmembrane auxiliary protein that modulates the voltage
      gated potassium channel KCNQ1. The KCNQ1/KCNE1 complex in cardiomyocytes
      exhibited slow activated potassium (I(ks)) currents. Recently, a novel 47-residue
      polypeptide toxin SSD609 was purified from Scolopendra subspinipes dehaani venom
      and showed I(ks) current inhibition. Here, chemically synthesized SSD609 was
      shown to exert I(ks) inhibition in extracted guinea pig cardiomyocytes and
      KCNQ1/KCNE1 current attenuation in CHO cells. The K(+) current attenuation of
      SSD609 showed decent selectivity among different auxiliary subunits. Solution
      nuclear magnetic resonance analysis of SSD609 revealed a distinctive three-helix
      conformation that was stabilized by a new disulfide bonding pattern as well as
      segregated surface charge distribution. Structure-activity studies demonstrated
      that negatively charged Glu19 in the amphipathic extracellular helix of KCNE1 was
      the key residue that interacted with SSD609. The distinctive three-helix
      centipede toxin SSD609 is known to be the first polypeptide toxin acting on
      channel auxiliary subunit KCNE1, which suggests a new type of pharmacological
      regulation for ion channels in cardiomyocytes.

PMID- 26307554
TI  - Acupuncture for pain control after Caesarean section: a prospective observational
      pilot study.
AB  - OBJECTIVE: Options for pharmacological analgesia in patients who have undergone
      Caesarean section (CS) are often restricted. Acupuncture is a promising tool for
      treating postoperative pain. We aimed to study the feasibility and acceptability
      of acupuncture as an additional method of analgesia in CS patients in a
      prospective observational pilot investigation. METHODS: Twenty-two patients
      scheduled for elective CS under spinal anaesthesia were enrolled according to set
      inclusion criteria. Each patient received auricular and body acupuncture with 20
      indwelling fixed needles according to previously validated protocols of
      acupuncture for postoperative analgesia. Pain intensity on an 11-point verbal
      rating scale (VRS-11, where 0=no pain and 10=maximal pain), analgesia-related
      side effects, time to mobilisation and Foley catheter removal after CS, and
      patients' compliance and satisfaction with treatment of pain on a 5-point VRS
      (VRS-5, where 1=excellent; 5=bad) were recorded. RESULTS: Twenty patients were
      included in the final analysis. One patient was disturbed by paraesthesia at the
      site of needling. All other patients tolerated acupuncture well. Pain intensity
      on movement on the first postoperative day was 4.3+/-2.4 (mean+/-SD; VRS-11) and
      decreased to 2.2+/-1.2 on the day of discharge. Patient satisfaction was 1.9+/
      0.8 (mean+/-SD; VRS-5) and compliance (rated by their nurses) was 1.5+/-0.5
      (mean+/-SD; VRS-5). CONCLUSIONS: Acupuncture for additional analgesia after CS
      was well accepted. The primary outcome measurement was feasible and allowed the
      sample size to be calculated for a future randomised controlled trial.

PMID- 26307555
TI  - Shape-Dependent Activity of Ceria for Hydrogen Electro-Oxidation in Reduced
      Temperature Solid Oxide Fuel Cells.
AB  - Single crystalline ceria nanooctahedra, nanocubes, and nanorods are
      hydrothermally synthesized, colloidally impregnated into the porous
      La0.9Sr0.1Ga0.8Mg0.2O3-delta (LSGM) scaffolds, and electrochemically evaluated as
      the anode catalysts for reduced temperature solid oxide fuel cells (SOFCs). Well
      defined surface terminations are confirmed by the high-resolution transmission
      electron microscopy--(111) for nanooctahedra, (100) for nanocubes, and both (110)
      and (100) for nanorods. Temperature-programmed reduction in H2 shows the highest
      reducibility for nanorods, followed sequentially by nanocubes and nanooctahedra.
      Measurements of the anode polarization resistances and the fuel cell power
      densities reveal different orders of activity of ceria nanocrystals at high and
      low temperatures for hydrogen electro-oxidation, i.e., nanorods > nanocubes >
      nanooctahedra at T <= 450  degrees C and nanooctahedra > nanorods > nanocubes at
      T >= 500  degrees C. Such shape-dependent activities of these ceria nanocrystals
      have been correlated to their difference in the local structure distortions and
      thus in the reducibility. These findings will open up a new strategy for design
      of advanced catalysts for reduced-temperature SOFCs by elaborately engineering
      the shape of nanocrystals and thus selectively exposing the crystal facets.

PMID- 26307556
TI  - The "5 a day" game: a nutritional intervention utilising innovative methodologies
      with primary school children.
AB  - The aim of this study was observing and improving children's eating habits
      through an edutainment technological platform. A single-group education
      intervention was carried out in primary schools in Parma and Milano, Italy. A
      total of 76 children (32 females and 44 males, 8-10 years old) were involved in a
      3-month nutritional program including lessons and educational videogames. Intakes
      of fruits, vegetables, juices and dietary total antioxidant capacity (TAC) were
      measured using 3-day food diaries before and after the intervention. The daily
      total consumption of fruit and vegetables increased from 421.8 (320.3) to 484.3
      (337.2) g/day (p = 0.016). Consequently, daily dietary TAC increased by 26%,
      rising from 1.4 (1.3) to 1.6 (1.3) mmol of Trolox equivalents (p = 0.006). The
      methods and, particularly, the use of technological tools proved to be effective
      in conducting an educational intervention in children aged 8-10 years old. 

PMID- 26307557
TI  - T helper (Th)-cytokines in the urine of patients with primary glomerulonephritis
      treated with immunosuppressive drugs: Can they predict outcome?
AB  - BACKGROUND: Glomerulonephritides (GNs) represent common causes of chronic kidney
      disease associated with a wide spectrum of clinical and histological features.
      Various factors that activate the inflammatory cascade are involved in the
      development of kidney injury. The aim of this study was to estimate the urinary
      excretion of pro-inflammatory (IL-2, INF-gamma, TNF-alpha, IL-6, IL-17) and anti
      inflammatory (IL-4, IL-10, TGF-beta1) cytokines, as well as the chemokine MCP-1
      in patients with various types of GN treated by immunosuppressive drugs and to
      identify any prognostic value of excreted cytokines for future renal function.
      PATIENTS AND METHODS: Ninety-seven patients (62 M/35 F, age 53.1 +/- 15.6 years)
      with primary glomerulonephritis and 32 healthy controls were studied. The
      original diagnoses were membranous nephropathy (MN, n=36), IgA nephropathy (IgAN,
      n=31) and minimal changes disease or focal segmental glomerulosclerosis
      (MCD/FSGS, n=30). All patients had been treated with immunosuppressive drugs and,
      at the time of measurement of urinary cytokine excretion, were either in clinical
      remission or still had active disease with persistent proteinuria. RESULTS: GN
      patients had significantly higher levels of all cytokines and MCP-1 compared to
      healthy controls. A strong positive correlation between TGF-beta1 and MCP-1
      concentrations was observed in all GN patients. Increased urinary excretion of
      all tested cytokines apart from TNF-alpha and TGF-beta1 was observed even in
      patients with clinical remission. The main difference between patients with
      proteinuria and those in clinical remission was the level of MCP-1 urinary
      excretion. The urinary excretion of MCP-1 and TGF-beta1 was significantly higher
      in patients with MN who showed deterioration of renal function over a follow-up
      period of five years. CONCLUSIONS: Increased levels of cytokines are observed in
      the urine of patients with different types of glomerulonephritis, even after the
      achievement of clinical remission with the administration of immunosuppressive
      drugs. Urinary excretion of MCP-1 and TGF-beta1 indicates the ongoing
      inflammatory and fibrotic processes in the kidney and is probably related to
      unfavourable outcomes.

PMID- 26307558
TI  - A Prospective, Randomized, Single-Blinded, Head-to-Head Long-Term Outcome Study,
      Comparing Intrathecal (IT) Boluses With Continuous Infusion Trialing Techniques
      Prior to Implantation of Drug Delivery Systems (DDS) for the Treatment of Severe
      Intractable Chronic Nonmalignant Pain.
AB  - OBJECTIVE: The study aims to compare intrathecal (IT) boluses to continuous
      infusion trialing techniques prior to implantation of drug delivery systems (DDS)
      for the treatment of severe intractable chronic nonmalignant pain. DESIGN: This
      is a prospective, randomized, head-to-head long-term outcome study. MATERIALS AND
      METHODS: Forty patients with comparable patient demographics were randomly
      assigned to two cohorts. Cohort A trialed with intermittent boluses; Cohort B
      trialed with continuous infusion. One patient failed trial in each group.
      Nineteen patients were implanted in each group. Follow-up was for 36 months with
      intervals at 6, 12, 18, 24, 36 months. The Brief Pain Inventory was used was used
      for assessment. OUTCOME MEASURES: We used the Brief Pain Inventory to measure
      pain (worst and average), physical function (walking, normal work, and general
      activity), behavioral function (mood, sleep, and relations with others), IT dose,
      and oral opioid use. RESULTS: We observed statistically significant reduction in
      pain and improvement of function in both cohorts following DDS implantation
      throughout the observation period. The IT dose remained virtually unchanged
      throughout as well, with overall limited dose escalation. Oral opioid use was
      significantly reduced. There was no statistically significant difference in
      prediction of trial success or long-term outcomes between the two cohorts.
      CONCLUSION: Low-dose IT opioids via DDS can provide significant and long-lasting
      reduction in pain, and improvement in function (physical and behavioral) for
      patients with chronic nonmalignant pain. The two trialing techniques tested,
      intermittent boluses, and continuous infusion delivered intrathecally showed no
      clinical significance difference in terms of predicting trial success or long
      term outcomes.

PMID- 26307559
TI  - Binding characteristics of molecularly imprinted polymers based on fungicides in
      hydroalcoholic media.
AB  - An iprodione-imprinted polymer was prepared by copolymerization of methacrylamide
      and ethylene glycol dimethacrylate using a noncovalent imprinting approach.
      Methacrylamide was chosen using molecular dynamics simulations. To concentrate
      iprodione from hydro-alcoholic solutions, batch sorption of iprodione on the
      imprinted polymer were conducted. The equilibrium time for iprodione sorption is
      20 min, and the corresponding kinetic mechanism follows the pseudo-second order
      indicating a strong interaction between iprodione and the imprinted polymer.
      Langmuir, Freundlich, and Dubinin-Radushkevich models were used to fit the
      isotherm of iprodione sorption. The imprinted polymer was found to be more
      efficient than the nonimprinted polymer for the uptake of iprodione, as revealed
      by its higher adsorption energy, affinity, and capacity. Finally, a selectivity
      study was conducted on the imprinted and the nonimprinted polymers to sorb three
      fungicides. It shows that the imprinted polymer could be used as a
      preconcentration phase in a multiresidue analysis of fungicides in hydroalcoholic
      medium. 

PMID- 26307560
TI  - A review of recent evidence in human studies of n-3 and n-6 PUFA intake on
      cardiovascular disease, cancer, and depressive disorders: does the ratio really
      matter?
AB  - Polyunsaturated fatty acids (PUFAs) have been considered of great interest for
      human health due to their potential anti-inflammatory action that may protect
      from a number of chronic-degenerative diseases with an inflammatory pathogenesis.
      This review aimed to report the most updated evidence of both n-3 and n-6 PUFAs
      effect on cardiovascular disease, cancer, and depression in humans. Attention has
      been also paid to those studies exploring the effects of the ratio intake.
      Results from pooled analyses of human studies reported a general positive effect
      of n-3 PUFAs intake on all outcomes considered. In contrast, the role of n-6
      PUFAs on human health needs to be better assessed in order to clearly identify
      which compound exerts beneficial/harmful effects. Only a limited number of
      clinical studies considered the n-3:n-6 PUFAs ratio, rather reporting contrasting
      results. A number of limitations when considering the ratio between these two
      families of PUFAs have risen. 

PMID- 26307561
TI  - miR-410 enhanced hESC-derived pancreatic endoderm transplant to alleviate
      gestational diabetes mellitus.
AB  - Gestational diabetes mellitus (GDM) is a condition commonly encountered during
      mid to late pregnancy with pathologic manifestations including hyperglycemia,
      hyperinsulinemia, insulin resistance, and fetal mal-development. The deficit and
      dysfunction of insulin secreting beta-cells are signature symptoms for GDM.
      Pancreatic progenitors derived from human embryonic stem cells (hESCs) were shown
      to be able to effectively treat diabetes in mice. In this study, we first
      identified that microRNA-410 (miR-410) directly targets lactate dehydrogenase A
      (LDHA), a gene selectively repressed in normal insulin secreting beta-cells.
      hESCs that can be induced to express miR-410 hence keeping LDHA levels in check
      were then differentiated in vitro into pancreatic endoderm, followed by
      transplantation into db/+ mouse model of GDM. The transplant greatly improved
      glucose metabolism and reproductive outcome of the pregnant females suffering
      from GDM. Our findings describe for the first time the method of combining miRNA
      with hESCs, providing proof of concept by employing genetically modified stem
      cell therapy for treating GDM. 

PMID- 26307562
TI  - Bone remodeling in the context of cellular and systemic regulation: the role of
      osteocytes and the nervous system.
AB  - Bone is a dynamic tissue that undergoes constant remodeling. The appropriate
      course of this process determines development and regeneration of the skeleton.
      Tight molecular control of bone remodeling is vital for the maintenance of
      appropriate physiology and microarchitecture of the bone, providing homeostasis,
      also at the systemic level. The process of remodeling is regulated by a rich
      innervation of the skeleton, being the source of various growth factors,
      neurotransmitters, and hormones regulating function of the bone. Although the
      course of bone remodeling at the cellular level is mainly associated with the
      activity of osteoclasts and osteoblasts, recently also osteocytes have gained a
      growing interest as the principal regulators of bone turnover. Osteocytes play a
      significant role in the regulation of osteogenesis, releasing sclerostin (SOST),
      an inhibitor of bone formation. The process of bone turnover, especially
      osteogenesis, is also modulated by extra-skeletal molecules. Proliferation and
      differentiation of osteoblasts are promoted by the brain-derived serotonin and
      hypothetically inhibited by its intestinal equivalent. The activity of SOST and
      serotonin is either directly or indirectly associated with the canonical Wnt/beta
      catenin signaling pathway, the main regulatory pathway of osteoblasts function.
      The impairment of bone remodeling may lead to many skeletal diseases, such as
      high bone mass syndrome or osteoporosis. In this paper, we review the most recent
      data on the cellular and molecular mechanisms of bone remodeling control, with
      particular emphasis on the role of osteocytes and the nervous system in this
      process. 

PMID- 26307563
TI  - Selective phosphorylation during early macrophage differentiation.
AB  - The differentiation of macrophages from monocytes is a tightly controlled and
      complex biological process. Although numerous studies have been conducted using
      biochemical approaches or global gene/protein profiling, the mechanisms of the
      early stages of differentiation remain unclear. Here we used SILAC-based
      quantitative proteomics approach to perform temporal phosphoproteome profiling of
      early macrophage differentiation. We identified a large set of phosphoproteins
      and grouped them as PMA-regulated and non-regulated phosphoproteins in the early
      stages of differentiation. Further analysis of the PMA-regulated phosphoproteins
      revealed that transcriptional suppression, cytoskeletal reorganization and cell
      adhesion were among the most significantly activated pathways. Some key involved
      regulators of these pathways are mTOR, MYB, STAT1 and CTNNB. Moreover, we were
      able to classify the roles and activities of several transcriptional factors
      during different differentiation stages and found that E2F is likely to be an
      important regulator during the relatively late stages of differentiation. This
      study provides the first comprehensive picture of the dynamic phosphoproteome
      during myeloid cells differentiation, and identifies potential molecular targets
      in leukemic cells. 

PMID- 26307564
TI  - Reducing Unintended Pregnancies Through Web-Based Reproductive Life Planning and
      Contraceptive Action Planning among Privately Insured Women: Study Protocol for
      the MyNewOptions Randomized, Controlled Trial.
AB  - BACKGROUND: The Affordable Care Act mandates that most women of reproductive age
      with private health insurance have full contraceptive coverage with no out-of
      pocket costs, creating an actionable time for women to evaluate their
      contraceptive choices without cost considerations. The MyNewOptions study is a
      three-arm, randomized, controlled trial testing web-based interventions aimed at
      assisting privately insured women with making contraceptive choices that are
      consistent with their reproductive goals. METHODS: Privately insured women
      between the ages of 18 and 40 not intending pregnancy were randomly assigned to
      one of three groups: 1) a reproductive life planning (RLP) intervention, 2) a
      reproductive life planning enriched with contraceptive action planning (RLP+)
      intervention, or 3) an information only control group. Both the RLP and RLP+
      guide women to identify their individualized reproductive goals and contraceptive
      method requirements. The RLP+ additionally includes a contraceptive action
      planning component, which uses if-then scenarios that allow the user to problem
      solve situations that make it difficult to be adherent to their contraceptive
      method. All three groups have access to a reproductive options library containing
      information about their contraceptive coverage and the attributes of alternative
      contraceptive methods. Women completed a baseline survey with follow-up surveys
      every 6 months for 2 years concurrent with intervention boosters. Study outcomes
      include contraceptive use and adherence. ClinicalTrials.gov identifier:
      NCT02100124. DISCUSSION: Results from the MyNewOptions study will demonstrate
      whether web-based reproductive life planning, with or without contraceptive
      action planning, helps insured women make patient-centered contraceptive choices
      compared with an information-only control condition.

PMID- 26307565
TI  - Why Women Sit: Determinants of Leisure Sitting Time for Working Women.
AB  - BACKGROUND: Sedentary behavior is associated with negative health consequences
      independent of physical activity levels. Evidence suggests the work environment
      promotes sedentary behavior regardless of sector, and that employees with
      occupations requiring longer sitting times differ only marginally in leisure
      sitting time from those with more active occupations. Because physical activity
      opportunities may be limited across many work settings, leisure sedentary time
      may be more easily replaced with physical activity. Understanding correlates of
      leisure sedentary behaviors could inform interventions, specifically for women
      who are among the least active in America. METHODS: Female employees at two
      universities completed online surveys (n = 156; mean age, 45.12 [SD = 12.5]; mean
      BMI, 26.7 kg/m(2) [SD = 5.9]; mean work hours/week, 43.7 [SD = 9.4]). Bivariate
      correlations and two hierarchical regression analyses were conducted to examine
      personal and behavioral correlates of weekday and weekend leisure sitting time.
      FINDINGS: Final regression models revealed that greater weekday leisure sitting
      time (R(2) = 0.307) was related with being older (p = .006), having fewer
      children (p = .001), self-reporting poorer health (p = .006), and greater weekend
      sitting time (p < .001). Greater weekend leisure sitting time (R(2) = 0.261) was
      related with greater work-related sitting time (p = .020) and greater weekday
      leisure sitting time (p < .001). Physical activity was not related with weekday
      or weekend leisure sitting time. CONCLUSIONS: The most prominent correlates of
      leisure sitting time were other types of sedentary behaviors. This suggests that
      sedentary time in one segment of life predicts time spent sitting in other areas
      of life. Future interventions should target decreasing sedentary behaviors during
      leisure time specifically, in addition to increasing physical activity behavior.

PMID- 26307566
TI  - The ProVIDe study: the impact of protein intravenous nutrition on development in
      extremely low birthweight babies.
AB  - BACKGROUND: Preterm birth and very small size at birth have long-term effects on
      neurodevelopment and growth. A relatively small percentage of extremely low
      birthweight babies suffer from severe neurological disability; however, up to 50%
      experience some neurodevelopmental or learning disability in childhood. Current
      international consensus is that increased protein intake in the neonatal period
      improves both neurodevelopment and growth, but the quantum of protein required is
      not known. This trial aims to assess whether providing an extra 1 to 2 g.kg(
      1).d(-1) protein in the first 5 days after birth will improve neurodevelopmental
      outcomes and growth in extremely low birthweight babies. METHODS/DESIGN: The
      ProVIDe study is a multicentre, two-arm, double-blind, parallel, randomised,
      controlled trial. In addition to standard intravenous nutrition, 430 babies with
      a birthweight of less than 1000 g who have an umbilical arterial line in situ
      will be randomised in 1:1 ratio to receive either an amino acid solution
      (TrophAmine(r)) or placebo (saline) administered through the umbilical arterial
      catheter for the first 5 days. Exclusion criteria are admission to neonatal
      intensive care more than 24 h after birth; multiple births of more than 2 babies;
      known chromosomal or genetic abnormality, or congenital disorder affecting
      growth; inborn error of metabolism, and in danger of imminent death. PRIMARY
      OUTCOME: Survival free from neurodevelopmental disability at 2 years' corrected
      age, where neurodevelopmental disability is defined as cerebral palsy, blindness,
      deafness, developmental delay (standardised score more than 1 SD below the mean
      on the cognitive, language or motor subscales of the Bayley Scales of Infant
      Development Edition 3), or Gross Motor Function Classification System score >= 1.
      SECONDARY OUTCOMES: Growth, from birth to 36 weeks' corrected gestational age, at
      neonatal intensive care discharge and at 2 years' corrected age; body composition
      at 36 to 42 weeks' corrected postmenstrual age and at 2 years' corrected age;
      neonatal morbidity, including length of stay; nutritional intake. DISCUSSION:
      This trial will provide the first direct evidence of the effects of giving
      preterm babies a higher intake of intravenous protein in the first week after
      birth on neurodevelopmental outcomes at 2 years corrected age. TRIAL
      REGISTRATION: Australian New Zealand Clinical Trials Registry:
      ACTRN12612001084875.

PMID- 26307567
TI  - Hypomyelination and developmental delay associated with VPS11 mutation in
      Ashkenazi-Jewish patients.
AB  - BACKGROUND: The genetic heterogeneity of developmental delay and cognitive
      impairment is vast. The endocytic network is essential for neural development and
      synaptic plasticity by regulating the sorting of numerous transmembrane proteins.
      Disruption of the pathway can lead to neuronal pathology. Endosomal biogenesis
      relies on two Rab proteins, Rab5 and Rab7, which bind to two hexameric tethering
      complexes, the endosomal class C core vacuole/endosome tethering complex (CORVET)
      and the late endosomal/lysosomal homotypic fusion and protein sorting complex
      (HOPS). Both complexes consist of four core proteins and differ by their specific
      Rab-binding proteins. OBJECTIVES: To identify the molecular basis of a
      neurological disease, which consists of global developmental stagnation at 3-8
      months, increasing appendicular spasticity, truncal hypotonia and acquired
      microcephaly, with variable seizure disorder, accompanied by thin corpus
      callosum, paucity of white matter and delayed myelination in eight patients from
      four unrelated Ashkenazi-Jewish (AJ) families. METHODS: Exome analysis,
      homozygosity mapping and Mup1-GFP transport assay in mutant yeast. RESULTS:
      Homozygosity for a missense mutation, p.Cys846Gly, in one of the endosomal
      biogenesis core proteins, VPS11, was identified in all the patients. This was
      shown to be a founder mutation with a carrier frequency of 0.6% in the AJ
      population. The homologous yeast mutant had moderate impairment of fusion of the
      late endosome to the vacuole in Mup1-GFP transport assay. CONCLUSIONS: We
      speculate that in neuronal cells, impairment of fusion of the late endosome to
      the vacuole would attenuate the degradation of plasma membrane receptors, thereby
      underlying the progressive neuronal phenotype in our patients. The VPS11
      p.Cys846Gly mutation should be added to the AJ carrier screening panel.

PMID- 26307568
TI  - Neurogenetic evidence in the courtroom: a randomised controlled trial with German
      judges.
AB  - BACKGROUND: Prominent court decisions and recent research suggest that
      introduction of neurogenetic evidence, for example, monoamine oxidase A alleles,
      may reduce the sentence of convicted psychopaths. Here, we are aiming to
      demonstrate that judges' response to neurogenetic evidence is highly influenced
      by the legal system in which they operate. METHODS: Participating German judges
      (n=372) received a hypothetical case vignette of aggravated battery, and were
      randomly assigned to expert testimonies that either involved a neurogenetic
      explanation of the offender's psychopathy or only a psychiatric diagnosis of
      psychopathy. Testimonies were presented either by the prosecution or defence.
      RESULTS: Neurogenetic evidence significantly reduced judges' estimation of legal
      responsibility of the convict. Nevertheless, the average prison sentence was not
      affected in the German legal system. Most interestingly, analysis of judges'
      reasoning revealed that neurogenetic arguments presented by the prosecution
      significantly increased the number of judges (23% compared with ~ 6%) ordering an
      involuntary commitment in a forensic psychiatric hospital. Such an involuntary
      commitment due to diminished or absent legal responsibility may last much longer
      than a prison sentence in the German legal system. CONCLUSIONS: Our data, thus,
      demonstrate the socially contingent nature of legal responses to neurogenetic
      evidence in criminal cases.

PMID- 26307569
TI  - Cerebral Oximetry as a Real-Time Monitoring Tool to Assess Quality of In-Hospital
      Cardiopulmonary Resuscitation and Post Cardiac Arrest Care.
AB  - BACKGROUND: Regional cerebral oxygen saturation (rSO2) as assessed by near
      infrared frontal cerebral spectroscopy decreases in circulatory arrest and
      increases with high-quality cardiopulmonary resuscitation. We hypothesized that
      higher rSO2 during cardiopulmonary resuscitation and after return of spontaneous
      circulation (ROSC) would predict survival to discharge and neurological recovery.
      METHODS AND RESULTS: This prospective case series included patients experiencing
      in-hospital cardiac arrest. Cerebral oximetry was recorded continuously from
      initiation of resuscitation until ROSC and up to 48 hours post-arrest.
      Relationships between oximetry data during these time periods and outcomes of
      resuscitation survival and survival to discharge were analyzed. The cohort
      included 27 patients. Nineteen (70.3%) achieved ROSC, and 8 (29.6%) survived to
      discharge. Median arrest duration was 20.8 minutes (range=8 to 74). There was a
      significant difference in rSO2 between resuscitation survivors and resuscitation
      nonsurvivors at initiation of the resuscitative efforts (35% versus 17.5%,
      P=0.03) and during resuscitation (36% versus 15%, P=0.0008). No significant
      association was observed between rSO2 at ROSC or during the post-arrest period
      and survival to discharge. Among patients who survived to discharge, there was no
      association between cerebral performance category and rSO2 at ROSC, during
      resuscitation, or post-arrest. CONCLUSIONS: Higher rSO2 levels at initiation of
      resuscitation and during resuscitation are associated with resuscitation survival
      and may reflect high-quality cardiopulmonary resuscitation. However, in this
      small series, rSO2 was not predictive of good neurological outcome. Larger
      studies are needed to determine whether this monitoring modality can be used to
      improve clinical outcomes.

PMID- 26307571
TI  - It's Time to Reassess the High-Density Lipoprotein (HDL) Hypothesis: CSL112, a
      Novel Promising Reconstituted HDL Formulation.

PMID- 26307570
TI  - Infusion of Reconstituted High-Density Lipoprotein, CSL112, in Patients With
      Atherosclerosis: Safety and Pharmacokinetic Results From a Phase 2a Randomized
      Clinical Trial.
AB  - BACKGROUND: CSL112 is a new formulation of human apolipoprotein A-I (apoA-I)
      being developed to reduce cardiovascular events following acute coronary
      syndrome. This phase 2a, randomized, double-blind, multicenter, dose-ranging
      trial represents the first clinical investigation to assess the safety and
      pharmacokinetics/pharmacodynamics of a CSL112 infusion among patients with stable
      atherosclerotic disease. METHODS AND RESULTS: Patients were randomized to single
      ascending doses of CSL112 (1.7, 3.4, or 6.8 g) or placebo, administered over a 2
      hour period. Primary safety assessments consisted of alanine aminotransferase or
      aspartate aminotransferase elevations >3* upper limits of normal and study drug
      related adverse events. Pharmacokinetic/pharmacodynamic assessments included apoA
      I plasma concentration and measures of the ability of serum to promote
      cholesterol efflux from cells ex vivo. Of 45 patients randomized, 7, 12, and 14
      received 1.7-, 3.4-, and 6.8-g CSL112, respectively, and 11 received placebo.
      There were no clinically significant elevations (>3* upper limit of normal) in
      alanine aminotransferase or aspartate aminotransferase. Adverse events were
      nonserious and mild and occurred in 5 (71%), 5 (41%), and 6 (43%) patients in the
      CSL112 1.7-, 3.4-, and 6.8-g groups, respectively, compared with 3 (27%) placebo
      patients. The imbalance in adverse events was attributable to vessel
      puncture/infusion-site bruising. CSL112 resulted in rapid (T(max)~2 hours) and
      dose-dependent increases in apoA-I (145% increase in the 6.8-g group) and total
      cholesterol efflux (up to 3.1-fold higher than placebo) (P<0.001). CONCLUSIONS:
      CSL112 infusion was well tolerated in patients with stable atherosclerotic
      disease. CSL112 immediately raised apoA-I levels and caused a rapid and marked
      increase in the capacity of serum to efflux cholesterol. This potential novel
      approach for the treatment of atherosclerosis warrants further investigation.
      CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique
      identifier: NCT01499420.

PMID- 26307572
TI  - Cerebral Oximetry and Cardiopulmonary Resuscitation.

PMID- 26307573
TI  - Irritant-Induced Paradoxical Vocal Fold Motion Disorder: Diagnosis and
      Management.
AB  - OBJECTIVES: To review our experience with the diagnosis and treatment of irritant
      induced paradoxical vocal fold motion disorder (IPVFMD). STUDY DESIGN:
      Retrospective chart review. SETTING: Tertiary academic referral center. SUBJECTS
      AND METHODS: Thirty-four cases that met IPVFMD criteria and 76 cases of non
      IPVFMD were selected from a database of patients with paradoxical vocal fold
      motion disorder-the diagnosis of which was made on the basis of flexible
      fiberoptic laryngoscopy and augmented by an odor challenge. Clinical charts were
      reviewed to document history of environmental allergies, pulmonary disease,
      gastroesophageal reflux, psychiatric disorder, fibromyalgia, tobacco use, alcohol
      use, dysphonia, cough, dysphagia, and treatment outcomes. RESULTS: There were no
      statistical differences between the IPVFMD and non-IPVFMD groups. Of the patients
      who were assigned and attended laryngeal control therapy, 13 (65%) reported
      improvement of symptoms. Symptom improvement increased to 100% in those patients
      who attended at least 2 laryngeal control therapy sessions. CONCLUSIONS: IPVFMD
      should be considered in patients presenting with respiratory symptoms after
      irritant exposure. Sensitivity of diagnosis can be improved via a standardized
      approach consisting of a careful history and physical examination, including
      laryngoscopy in the presence of triggers. Laryngeal control therapy is a well
      tolerated and effective method of managing IPVFMD.

PMID- 26307574
TI  - Bedside Injection Medialization Laryngoplasty in Immediate Postoperative
      Patients.
AB  - OBJECTIVES: The morbidity of glottic insufficiency resulting from unilateral
      vocal fold immobility may significantly compromise postoperative recovery in
      patients with decreased pulmonary reserve or inability to protect their airway.
      Injection medialization laryngoplasty is an effective means of treating glottic
      insufficiency due to unilateral vocal fold immobility. The purpose of this study
      is to present our experience with bedside transoral injection medialization
      laryngoplasty in the immediate postoperative period. STUDY DESIGN: Case series
      with chart review. SETTING: Academic tertiary care hospital. SUBJECTS AND
      METHODS: Patient demographics, clinical characteristics, procedural details, and
      short-term outcome measures of oral intake were recorded in a cohort of 68
      patients over 5 years with unilateral vocal cord paralysis who underwent
      injection medialization as a bedside procedure in the immediate postoperative
      period. RESULTS: Mean time to injection was 8.2 days postoperatively. At the time
      of injection, 40 of 68 patients were nil per os. Seventy percent (28 of 40) had
      their diet advanced to adequate oral intake within 5 days of injection. Greater
      than half of the injections (36 of 68) were performed in the intensive care unit.
      No complications were noted, and all patients in this cohort were able to
      tolerate the bedside injection. CONCLUSION: Bedside injection medialization
      laryngoplasty in the immediate postoperative period via the transoral approach
      can be performed in patients, even in the intensive care unit, while on
      anticoagulation, and may be of benefit for hospitalized patients with unilateral
      vocal fold immobility. Further studies quantifying improvement in voice and
      swallowing data are merited.

PMID- 26307575
TI  - A Meta-analysis of Central Lymph Node Metastasis for Predicting Lateral
      Involvement in Papillary Thyroid Carcinoma.
AB  - OBJECTIVE: Whether central lymph node metastasis is a reliable indicator of
      lateral lymph node metastasis in papillary thyroid carcinoma remains obscure. To
      investigate the value of central lymph node metastasis for predicting lateral
      compartment involvement, we performed a meta-analysis of published studies. DATA
      SOURCES: A systematic literature search of PubMed, EMBASE, and Chinese National
      Knowledge Infrastructure databases was completed, and the reference lists of the
      identified articles and prior relevant reviews were examined. REVIEW METHODS: Two
      reviewers extracted data and assessed the quality of eligible studies
      independently. Odds ratios and 95% confidence intervals were pooled through a
      random effects meta-analysis model. RESULTS: Twenty-one studies were eligible and
      further analyzed in this meta-analysis. The risk of lateral lymph node metastasis
      was significantly higher in the central lymph node-positive group than in the
      negative group (odds ratio = 7.64, 95% confidence interval: 5.59-10.44), with
      moderate heterogeneity across studies (P = .007, I(2) = 48.6%). Subgroup analyses
      and sensitivity analysis suggested that the results were consistent and credible.
      However, Begg's funnel plot and Egger linear regression test revealed a
      likelihood of publication bias (P = .000). CONCLUSION: This meta-analysis
      suggests that central lymph node metastasis is valuable for predicting lateral
      compartment involvement in patients with papillary thyroid carcinoma. For those
      patients with central lymph node metastasis, additional attention should be paid
      to the lateral neck, as the risk of lateral lymph node metastasis was
      significantly higher in the central lymph node-positive group than in the
      negative group. Further studies regarding appropriate management for patients
      with high risk of lateral involvement are needed.

PMID- 26307576
TI  - Reflections on the Changing Platform of Education for the Budding
      Otolaryngologist.
AB  - Learning is a key component to developing and maintaining competency as a
      physician. Traditional approaches, such as textbooks, lectures, journal articles,
      and cadaver laboratories, have been instrumental. With the ease in accessing
      information, especially via the Internet, this article discusses innovative
      educational strategies that have evolved from this. 

PMID- 26307577
TI  - Early T Stage Salivary Duct Carcinoma: Outcomes and Implications for Patient
      Counseling.
AB  - Salivary duct carcinoma (SDC) is a rare salivary malignancy that often presents
      at advanced stage. Outcomes of low T stage patients with SDC have not been
      previously examined in detail. We queried our institution's cancer database and
      identified 28 patients with SDC in situ or T1/T2 SDC. A retrospective chart
      review was performed, followed by comparison of clinicopathologic features with N
      stage, disease-free survival, and overall survival. Patients tended to be male,
      in their sixties, with a high incidence of regional metastases, as in prior
      reports. Five-year disease-free and overall survival were 49%. Median disease
      free survival was 3.24 years, and overall survival was 4.65 years. Parotid
      location, vascular invasion, facial nerve sacrifice, and extracapsular extension
      were associated with worse survival. This study provides practical information
      for counseling of patients who undergo surgery for a parotid mass and are found
      to have this aggressive malignancy. 

PMID- 26307578
TI  - Quantitative Vestibular Labyrinthine Otopathology in Temporal Bones with
      Vestibular Schwannoma.
AB  - OBJECTIVE: Dizziness associated with vestibular schwannoma is usually ascribed to
      retrolabyrinthine mechanisms. The goal of this study was to determine if
      quantitative peripheral vestibular (labyrinthine) otopathology was present in a
      series of patients with vestibular schwannoma. STUDY DESIGN: Comparative human
      temporal bone study. SETTING: Otopathology laboratory. SUBJECTS AND METHODS:
      Temporal bones from 12 subjects with unilateral sporadic vestibular schwannoma
      were included. Based on differential interference contrast microscopy, type I and
      II vestibular hair cell counts were performed on each vestibular sense organ with
      minimal autolysis in which the neuroepithelium was oriented perpendicular to the
      plane of section. Hair cell densities (cells per 0.01-mm(2) surface area) and the
      presence of endolymphatic hydrops and precipitate within the endolymph or
      perilymph were compared between the tumor ears and the contralateral (control)
      ears. RESULTS: Compared with the contralateral ears, vestibular schwannoma ears
      had significantly more endolymphatic hydrops (P = .049) and precipitate in the
      endolymph and perilymph (P = .005), lower densities of type I and II vestibular
      hair cells in the lateral canal cristae (mean differences, respectively: 25.2 [P
      = .001] and 10.8 [P < .001]) and utricle (mean differences, respectively: 26.8
      and 10.4 [P < .001]), and lower densities of type I hair cells and the same
      density of type II hair cells in the saccule (mean differences, respectively:
      26.5 [P < .001] and 0.9 [P = .46]). CONCLUSION: Peripheral vestibular
      otopathology, manifested as reductions of vestibular hair cell densities, was
      identified in ears with vestibular schwannoma. Labyrinthine as well as
      retrolabyrinthine pathology may contribute to tumor-related vestibular
      dysfunction.

PMID- 26307579
TI  - Type I Thyroplasty in Previously Irradiated Patients: Assessing Safety and
      Efficacy.
AB  - OBJECTIVES: (1) Review and report our experience performing medialization
      thyroplasty (MT) in previously irradiated patients and (2) compare complications
      and voice outcomes in 2 cohorts (irradiated vs nonradiated) to evaluate safety
      and efficacy. STUDY DESIGN: Case series with chart review. SETTING: Academic
      medical center. SUBJECTS: All patients (44 total) who underwent MT from 2011 to
      2015. METHODS: Demographic data, complications, and acoustic and subjective voice
      outcome parameters were collected. The complication rates and voice outcome
      results were compared between 2 cohorts: patients with a history of radiation to
      the neck versus those with no radiation history. RESULTS: There were 7 previously
      irradiated patients and 37 nonradiated patients, with median follow-up of 314 and
      538 days, respectively. One complication was noted in each group, and this
      complication rate was not significantly different (P = .26). Both cohorts
      demonstrated significant postoperative improvement in subjective voice assessment
      (P = .04, P < .0001) as well as maximum phonation time (P = .02, .001) when
      compared with preoperative data. CONCLUSIONS: Our study suggests that MT can be
      safely and effectively performed in irradiated patients. We found no
      statistically significant difference in the safety of performing MT in irradiated
      versus nonradiated patients, and there was significant improvement in subjective
      voice parameters and maximum phonation time in both groups. A larger prospective
      study is required to statistically determine whether the significant improvements
      in objective parameters seen in the nonradiated group are present in irradiated
      patients as well.

PMID- 26307580
TI  - Perioperative Management of Antithrombotic Therapy in Common Otolaryngologic
      Surgical Procedures: State of the Art Review.
AB  - OBJECTIVE: The perioperative management of patients undergoing otolaryngologic
      procedures is increasingly complicated by the use of newer antithrombotic agents.
      Furthermore, with advances in anesthesia and surgical technique,
      otolaryngologists are presented with the challenge of operating on patients with
      advanced comorbid diseases. The objective of this review is to provide evidence
      based recommendations on perioperative antithrombotic management for common
      otolaryngologic procedures. DATA SOURCES: PubMed/MEDLINE. REVIEW METHODS:
      Selected literature on patient-specific thromboembolic risk, rate of bleeding
      complications in otolaryngologic procedures, and the interruption of
      antithrombotic therapy is reviewed and interpreted by expert opinion.
      CONCLUSIONS: By stratifying patients into either low thromboembolic risk (<= 5%)
      or high thromboembolic risk (> 5%) and interpreting this in the context of
      procedural bleed risk and potential clinical consequences in the event of a
      bleed, otolaryngologists can make evidence-based decisions to determine the
      appropriate perioperative management of antithrombotic therapy. IMPLICATIONS FOR
      PRACTICE: When the perioperative management of antithrombotic therapy is being
      decided, 3 critical factors must be considered systematically: the patient's
      inherent thromboembolic risk, the risk and potential consequences of bleeding
      related to the procedure, and the timing of interruption of thromboembolic
      therapy.

PMID- 26307581
TI  - A Pediatric Grading Scale for Lingual Tonsil Hypertrophy.
AB  - Lingual tonsil hypertrophy (LTH) is a common finding for children with residual
      obstructive sleep apnea (OSA) following an adenotonsillectomy. Secondary to the
      significant morbidity associated with OSA, identification and treatment of
      residual OSA are paramount. A dedicated LTH grading scale for children does not
      exist. The current adult LTH scale is impractical for children. Imaging is not
      routine for children, since it frequently requires sedation. We present a
      pediatric LTH grading scale with substantial interrater reliability to facilitate
      standardization of endoscopy findings and promote outcomes-based research for OSA
      surgery in children. 

PMID- 26307582
TI  - Shear Wave Elastography in the Diagnosis of Thyroid Nodules with Coexistent
      Chronic Autoimmune Hashimoto's Thyroiditis.
AB  - OBJECTIVE: To evaluate the diagnostic performance of shear wave elastography
      (SWE) in the differentiation of malignant and benign thyroid nodules with
      coexistent Hashimoto's thyroiditis (HT). STUDY DESIGN: Case series with chart
      review. SETTING: Tertiary general hospital. SUBJECTS AND METHODS: From September
      2012 to January 2014, conventional ultrasound and SWE were performed on 243
      patients with 286 thyroid nodules with histologic results. The HT group consisted
      of 93 patients with 117 nodules. The non-HT group consisted of 140 patients with
      169 nodules. RESULTS: In the benign and malignant nodules, there were no
      significant differences of the mean, minimum, or maximum SWE values between HT
      and non-HT groups (P = .158-.945). However, SWE values of extranodular tissue
      were significantly higher in the HT group (P = .000-.011). In the HT group, the
      maximum SWE value showed the highest area under the receiver operating
      characteristic curve (0.817; 95% confidence interval, .735-.900), and there were
      no significant differences when compared with other SWE parameters (P = .669
      .848). In the multivariate analysis, hypoechogenicity (odds ratio = 9.855, P =
      .002), microcalcification (odds ratio = 3.977, P = .046), and maximum SWE value
      (odds ratio = 40.712, P < .001) were independent predictors of thyroid
      malignancy. CONCLUSIONS: SWE could be performed to obtain a differential
      diagnosis between malignant and benign thyroid nodules, including nodules with
      coexistent HT. Although all the SWE parameters within a 2-mm region of interest
      that was placed on the stiffest region could be applied, we suggest that the
      maximum value of nodules harbored within a Hashimoto's gland be used.

PMID- 26307583
TI  - Increased Pharyngeal Reflux in Patients Treated for Laryngeal Cancer: A Pilot
      Study.
AB  - OBJECTIVE: Laryngopharyngeal reflux may cause significant morbidity in the head
      and neck cancer population. The goal was to determine if pharyngeal reflux is
      increased as a result of treatment for laryngeal cancer. STUDY DESIGN: A
      prospective clinical trial. SETTING: Tertiary care center. SUBJECTS: Head and
      neck cancer patients treated at LSU Health-Shreveport with a plan for total
      laryngectomy. METHODS: Pharyngeal pH probes with resultant reflux scores were
      utilized in patients with laryngeal/pharyngeal cancer with a plan for total
      laryngectomy. RESULTS: Twenty-four patients were enrolled, of whom 10 underwent
      postlaryngectomy pH probe monitoring. The mean upright Ryan score for patients
      with prior radiotherapy was 238.4 (n = 8), compared with 22.0 (n = 16) in those
      without prior radiotherapy (P = .02). The supine score was 12.7 in the
      radiotherapy group and 2.7 in those without radiotherapy (P = .12). For those who
      completed the postlaryngectomy pH study (n = 10), the mean preoperative upright
      Ryan score was 106.32 +/- 279.1 versus a postoperative score of 209.0 +/- 352.6
      (P = .04). The mean supine preoperative Ryan score in this group was 3.9 +/-
      3.47, as opposed to 8.1 +/- 9.6 postoperatively (P = .13) CONCLUSIONS: This study
      suggests that treatment of laryngeal cancer may increase the incidence of
      pharyngeal reflux. Consider screening for reflux in patients previously treated
      for laryngeal cancer.

PMID- 26307584
TI  - BMP-7 Induces Adult Human Pancreatic Exocrine-to-Endocrine Conversion.
AB  - The exocrine pancreas can give rise to endocrine insulin-producing cells upon
      ectopic expression of key transcription factors. However, the need for genetic
      manipulation remains a translational hurdle for diabetes therapy. Here we report
      the conversion of adult human nonendocrine pancreatic tissue into endocrine cell
      types by exposure to bone morphogenetic protein 7. The use of this U.S. Food and
      Drug Administration-approved agent, without any genetic manipulation, results in
      the neogenesis of clusters that exhibit high insulin content and glucose
      responsiveness both in vitro and in vivo. In vitro lineage tracing confirmed that
      BMP-7-induced insulin-expressing cells arise mainly from extrainsular PDX-1(+),
      carbonic anhydrase II(-) (mature ductal), elastase 3a (acinar)(-) , and insulin(
      ) subpopulations. The nongenetic conversion of human pancreatic exocrine cells to
      endocrine cells is novel and represents a safer and simpler alternative to
      genetic reprogramming. 

PMID- 26307585
TI  - Adipocyte Metrnl Antagonizes Insulin Resistance Through PPARgamma Signaling.
AB  - Adipokines play important roles in metabolic homeostasis and disease. We have
      recently identified a novel adipokine Metrnl, also known as Subfatin, for its
      high expression in subcutaneous fat. Here, we demonstrate a prodifferentiation
      action of Metrnl in white adipocytes. Adipocyte-specific knockout of Metrnl
      exacerbates insulin resistance induced by high-fat diet (HFD), whereas adipocyte
      specific transgenic overexpression of Metrnl prevents insulin resistance induced
      by HFD or leptin deletion. Body weight and adipose content are not changed by
      adipocyte Metrnl. Consistently, no correlation is found between serum Metrnl
      level and BMI in humans. Metrnl promotes white adipocyte differentiation,
      expandability, and lipid metabolism and inhibits adipose inflammation to form
      functional fat, which contributes to its activity against insulin resistance. The
      insulin sensitization of Metrnl is blocked by PPARgamma inhibitors or knockdown.
      However, Metrnl does not drive white adipose browning. Acute intravenous
      injection of recombinant Metrnl has no hypoglycemic effect, and 1-week
      intravenous administration of Metrnl is unable to rescue insulin resistance
      exacerbated by adipocyte Metrnl deficiency. Our results suggest adipocyte Metrnl
      controls insulin sensitivity at least via its local autocrine/paracrine action
      through the PPARgamma pathway. Adipocyte Metrnl is an inherent insulin sensitizer
      and may become a therapeutic target for insulin resistance. 

PMID- 26307586
TI  - Pancreatic beta-Cell Adaptive Plasticity in Obesity Increases Insulin Production
      but Adversely Affects Secretory Function.
AB  - Pancreatic beta-cells normally produce adequate insulin to control glucose
      homeostasis, but in obesity-related diabetes, there is a presumed deficit in
      insulin production and secretory capacity. In this study, insulin production was
      assessed directly in obese diabetic mouse models, and proinsulin biosynthesis was
      found to be contrastingly increased, coupled with a significant expansion of the
      rough endoplasmic reticulum (without endoplasmic reticulum stress) and Golgi
      apparatus, increased vesicular trafficking, and a depletion of mature beta
      granules. As such, beta-cells have a remarkable capacity to produce substantial
      quantities of insulin in obesity, which are then made available for immediate
      secretion to meet increased metabolic demand, but this comes at the price of
      insulin secretory dysfunction. Notwithstanding, it can be restored. Upon exposing
      isolated pancreatic islets of obese mice to normal glucose concentrations, beta
      cells revert back to their typical morphology with restoration of regulated
      insulin secretion. These data demonstrate an unrealized dynamic adaptive
      plasticity of pancreatic beta-cells and underscore the rationale for transient
      beta-cell rest as a treatment strategy for obesity-linked diabetes. 

PMID- 26307587
TI  - Genetic Evidence for a Causal Role of Obesity in Diabetic Kidney Disease.
AB  - Obesity has been posited as an independent risk factor for diabetic kidney
      disease (DKD), but establishing causality from observational data is problematic.
      We aimed to test whether obesity is causally related to DKD using Mendelian
      randomization, which exploits the random assortment of genes during meiosis. In
      6,049 subjects with type 1 diabetes, we used a weighted genetic risk score (GRS)
      comprised of 32 validated BMI loci as an instrument to test the relationship of
      BMI with macroalbuminuria, end-stage renal disease (ESRD), or DKD defined as
      presence of macroalbuminuria or ESRD. We compared these results with cross
      sectional and longitudinal observational associations. Longitudinal analysis
      demonstrated a U-shaped relationship of BMI with development of macroalbuminuria,
      ESRD, or DKD over time. Cross-sectional observational analysis showed no
      association with overall DKD, higher odds of macroalbuminuria (for every 1
      kg/m(2) higher BMI, odds ratio [OR] 1.05, 95% CI 1.03-1.07, P < 0.001), and lower
      odds of ESRD (OR 0.95, 95% CI 0.93-0.97, P < 0.001). Mendelian randomization
      analysis showed a 1 kg/m(2) higher BMI conferring an increased risk in
      macroalbuminuria (OR 1.28, 95% CI 1.11-1.45, P = 0.001), ESRD (OR 1.43, 95% CI
      1.20-1.72, P < 0.001), and DKD (OR 1.33, 95% CI 1.17-1.51, P < 0.001). Our
      results provide genetic evidence for a causal link between obesity and DKD in
      type 1 diabetes. As obesity prevalence rises, this finding predicts an increase
      in DKD prevalence unless intervention should occur. 

PMID- 26307589
TI  - Importance of HMBC and NOE 2D NMR techniques for the confirmation of
      regioselectivity.

PMID- 26307588
TI  - Role of PKCdelta in Insulin Sensitivity and Skeletal Muscle Metabolism.
AB  - Protein kinase C (PKC)delta has been shown to be increased in liver in obesity
      and plays an important role in the development of hepatic insulin resistance in
      both mice and humans. In the current study, we explored the role of PKCdelta in
      skeletal muscle in the control of insulin sensitivity and glucose metabolism by
      generating mice in which PKCdelta was deleted specifically in muscle using Cre
      lox recombination. Deletion of PKCdelta in muscle improved insulin signaling in
      young mice, especially at low insulin doses; however, this did not change glucose
      tolerance or insulin tolerance tests done with pharmacological levels of insulin.
      Likewise, in young mice, muscle-specific deletion of PKCdelta did not rescue high
      fat diet-induced insulin resistance or glucose intolerance. However, with an
      increase in age, PKCdelta levels in muscle increased, and by 6 to 7 months of
      age, muscle-specific deletion of PKCdelta improved whole-body insulin sensitivity
      and muscle insulin resistance and by 15 months of age improved the age-related
      decline in whole-body glucose tolerance. At 15 months of age, M-PKCdeltaKO mice
      also exhibited decreased metabolic rate and lower levels of some proteins of the
      OXPHOS complex suggesting a role for PKCdelta in the regulation of mitochondrial
      mass at older age. These data indicate an important role of PKCdelta in the
      regulation of insulin sensitivity and mitochondrial homeostasis in skeletal
      muscle with aging. 

PMID- 26307590
TI  - Clarivein mechanochemical ablation of the great and small saphenous vein: Early
      treatment outcomes of two hospitals.
AB  - OBJECTIVES: Mechanochemical endovenous ablation is a novel technique for the
      treatment of great saphenous vein and small saphenous vein incompetence which
      combines mechanical injury of the endothelium with simultaneous infusion of
      liquid sclerosant. The main objective of this study was to evaluate early
      occlusion. METHODS: All consecutive patients who were eligible for the treatment
      with mechanochemical endovenous ablation were included. Inclusion period was from
      the introduction of the device in the hospitals (September 2011 and December
      2011) until December 2012. RESULTS: A total of 449 patients were included
      representing 570 incompetent veins. In 506 treated veins, duplex ultrasonography
      was performed at follow-up: 457 veins (90%) were occluded at a follow-up of 6 to
      12 weeks. In univariate and multivariate analysis, failure of treated great
      saphenous vein was associated with saphenofemoral junction incompetence (OR 4;
      95% CI 1.0-17.1, P = 0.049). CONCLUSIONS: The Clarivein device proves to be safe
      and had a high short-term technical effectiveness.

PMID- 26307591
TI  - Advances in clinical trials for movement disorders.
AB  - In the past several years, there have been several innovations in the design of
      clinical trials assessing new therapies for patients with movement disorders.
      These include attempts to address difficulties in conducting clinical trials in
      treated patients in the advanced stages of their illness, demonstrating disease
      modifying effects or a reduction in the development of cumulative disability, and
      assessing the effects of interventions in patients in the premanifest state of
      their disease. In addition, there have been advances in clinical trial
      methodologies and changes in regulatory guidelines that permit the performance of
      more efficient studies, with a reduction in the cost and duration of the
      development period. These will be reviewed in the present article. (c) 2015
      International Parkinson and Movement Disorder Society. 

PMID- 26307593
TI  - Differences in foraging ecology align with genetically divergent ecotypes of a
      highly mobile marine top predator.
AB  - Foraging differentiation within a species can contribute to restricted gene flow
      between ecologically different groups, promoting ecological speciation. Galapagos
      sea lions (Zalophus wollebaeki) show genetic and morphological divergence between
      the western and central archipelago, possibly as a result of an ecologically
      mediated contrast in the marine habitat. We use global positioning system (GPS)
      data, time-depth recordings (TDR), stable isotope and scat data to compare
      foraging habitat characteristics, diving behaviour and diet composition of
      Galapagos sea lions from a western and a central colony. We consider both
      juvenile and adult life stages to assess the potential role of ontogenetic shifts
      that can be crucial in shaping foraging behaviour and habitat choice for life. We
      found differences in foraging habitat use, foraging style and diet composition
      that aligned with genetic differentiation. These differences were consistent
      between juvenile and adult sea lions from the same colony, overriding age
      specific behavioural differences. Our study contributes to an understanding of
      the complex interaction of ecological condition, plastic behavioural response and
      genetic make-up of interconnected populations.

PMID- 26307594
TI  - The 'credibility paradox' in China's science communication: Views from scientific
      practitioners.
AB  - In contrast to increasing debates on China's rising status as a global scientific
      power, issues of China's science communication remain under-explored. Based on 21
      in-depth interviews in three cities, this article examines Chinese scientists'
      accounts of the entangled web of influence which conditions the process of how
      scientific knowledge achieves (or fails to achieve) its civic authority. A main
      finding of this study is a 'credibility paradox' as a result of the over
      politicisation of science and science communication in China. Respondents report
      that an absence of visible institutional endorsements renders them more public
      credibility and better communication outcomes. Thus, instead of exploiting formal
      channels of science communication, scientists interviewed were more keen to act
      as 'informal risk communicators' in grassroots and private events. Chinese
      scientists' perspectives on how to earn public support of their research sheds
      light on the nature and impact of a 'civic epistemology' in an authoritarian
      state. 

PMID- 26307595
TI  - Extracorporeal Membrane Oxygenation in Pregnancy.
AB  - AIM: Adult respiratory distress syndrome (ARDS) may pose specific challenges in
      pregnant women, including the need for prone decubitus ventilation and
      extracorporeal membrane oxygenation (ECMO). We present our experience with ECMO
      during pregnancy and review the literature on this topic. METHODS: We performed a
      systematic literature review using the MEDLINE-NIH database. Papers describing
      single cases or clinical series of pregnant women treated with veno-venous ECMO
      for ARDS were retrieved; the clinical features and maternal and infant outcomes
      were presented in aggregate form. RESULTS: We describe the case of a 32-year-old
      primigravida who received ECMO starting at the 28th gestation week due to A/H1N1
      influenza-related ARDS. This strategy allowed saving both mother and child;
      normal recovery without sequelae was evident at one year. The systematic review
      included 29 reported cases of ECMO employment during pregnancy; A/H1N1 influenza
      was the etiology of ARDS in 79% of cases. Maternal and infant mortality may reach
      28%, while the rate of complications during ECMO support reaches 57%.
      CONCLUSIONS: ECMO is a viable treatment for severe ARDS during pregnancy, after
      failure of other therapeutic strategies; the risk of spontaneous gynecological
      bleeding is limited. Issues remain about the timing of ECMO implantation and the
      management of gestation. Close fetal assessment and multidisciplinary discussion
      are pivotal for decision-making.

PMID- 26307596
TI  - Time-resolved luminescence biosensor for continuous activity detection of protein
      acetylation-related enzymes based on DNA-sensitized terbium(III) probes.
AB  - Protein acetylation of histone is an essential post-translational modification
      (PTM) mechanism in epigenetic gene regulation, and its status is reversibly
      controlled by histone acetyltransferases (HATs) and histone deacetylases (HDACs).
      Herein, we have developed a sensitive and label-free time-resolved luminescence
      (TRL) biosensor for continuous detection of enzymatic activity of HATs and HDACs,
      respectively, based on acetylation-mediated peptide/DNA interaction and
      Tb(3+)/DNA luminescent probes. Using guanine (G)-rich DNA-sensitized Tb(3+)
      luminescence as the output signal, the polycationic substrate peptides interact
      with DNA with high affinity and subsequently replace Tb(3+), eliminating the
      luminescent signal. HAT-catalyzed acetylation remarkably reduces the positive
      charge of the peptides and diminishes the peptide/DNA interaction, resulting in
      the signal on detection via recovery of DNA-sensitized Tb(3+) luminescence. With
      this TRL sensor, HAT (p300) can be sensitively detected with a wide linear range
      from 0.2 to 100 nM and a low detection limit of 0.05 nM. The proposed sensor was
      further used to continuously monitor the HAT activity in real time. Additionally,
      the TRL biosensor was successfully applied to evaluating HAT inhibition by two
      specific inhibitors, anacardic acid and C464, and satisfactory Z'-factors above
      0.73 were obtained. Moreover, this sensor is feasible to continuously monitor the
      HDAC (Sirt1)-catalyzed deacetylation with a linear range from 0.5 to 500 nM and a
      detection limit of 0.5 nM. The proposed sensor is a convenient, sensitive, and
      mix-and-read assay, presenting a promising platform for protein acetylation
      targeted epigenetic research and drug discovery. 

PMID- 26307597
TI  - Screening for thrombophilia does not identify patients at risk of portal or
      splenic vein thrombosis following laparoscopic splenectomy.
AB  - BACKGROUND: Portal and/or splenic vein thrombosis (PSVT) is a potentially lethal
      complication of splenectomy for hematologic disease. Known risk factors for PSVT
      include malignancy and splenomegaly. While these patients are believed to be
      hypercoagulable, the specific mechanism is unclear. The aim of this study is to
      evaluate whether specific acquired prothrombotic risk factors contribute to the
      development of PSVT following laparoscopic splenectomy (LS). METHODS: Consecutive
      patients undergoing LS were prospectively studied between 2005 and 2013.
      Preoperatively, patients were screened for prothrombotic states and surveillance
      duplex ultrasonography was performed between 1 week and 1 month postoperatively
      to assess for PSVT. The association between baseline prothrombotic disorders and
      PSVT was explored using descriptive statistics. RESULTS: Sixty-eight patients
      were included in the analysis, and 17 (25 %) of these developed PSVT. There were
      no differences in patients with and without PSVT with respect to age, body mass
      index, gender or surgical time. Preoperative spleen size, as determined by
      diagnostic imaging, and intraoperative blood transfusion were associated with
      PSVT. Seven of 9 patients (78 %) with massive splenomegaly (>20 cm) developed
      PSVT compared with 4 of 13 patients (31 %) with moderate splenomegaly (15-20 cm)
      and 6 of 45 patients (13 %) without (p < 0.001). Abnormalities in baseline
      prothrombotic screening tests were common, with 52 patients (75 %) demonstrating
      at least one; however, none were associated with the development of PSVT.
      CONCLUSION: In patients scheduled for LS, screening for prothrombotic states is
      not useful to identify patients at risk of development of PSVT. Preoperative
      spleen size and blood transfusion were predictive of PSVT formation.

PMID- 26307598
TI  - Predictors of readmission after laparoscopic gastric bypass and sleeve
      gastrectomy: a comparative analysis of ACS-NSQIP database.
AB  - BACKGROUND: Readmission rate is an indicator of quality in surgical practice. We
      aimed to determine the predictors of unplanned early readmissions following
      stapling bariatric surgeries. METHODS: From the American College of Surgeons
      National Surgical Quality Improvement Program database, we identified morbidly
      obese patients, who underwent either laparoscopic sleeve gastrectomy (LSG) or
      laparoscopic Roux-en-Y gastric bypass (LRYGB) in 2012 and 2013. Demographic,
      comorbidities, operative and postoperative parameters of the readmitted (within
      30 days) and non-readmitted patients were evaluated using a multivariate logistic
      regression analysis. RESULTS: A total of 35,655 patients (17,101 LSG and 18,554
      LRYGB) were analyzed. Of those, 1758 patients (4.9 %) were readmitted within 30
      days of surgery. Multivariate analysis showed the following significant
      predictors for readmission: Non-Hispanic black ethnicity (OR: 1.56, 95 % CI:1.34
      1.81), Hispanic ethnicity (OR: 1.29, 95 % CI:1.05-1.58), totally or partially
      dependent functional status (OR: 1.94, 95 % CI:1.06-3.55), higher preoperative
      creatinine (OR: 1.13, 95 % CI:1.04-1.22), lower serum albumin (OR: 0.78, 95 %
      CI:0.68-0.90), diabetes mellitus on insulin (OR: 1.28, 95 % CI:1.09-1.51),
      steroid or immunosuppressant use for a chronic condition (OR: 1.61, 95 % CI:1.11
      2.33), history of cardiac disease with intervention (OR: 2.05, 95 % CI:1.10
      3.83), bleeding disorders (OR: 1.71, 95 % CI:1.15-2.54), LRYGB versus LSG (OR:
      1.63, 95 % CI:1.44-1.85), longer operative time (OR: 1.13, 95 % CI:1.07-1.20),
      concurrent splenectomy (OR: 4.10, 95 % CI:1.05-16.01), and occurrence of any
      postoperative complication during index admission (OR: 2.61, 95 % CI:1.99-3.42).
      CONCLUSIONS: Ethnicity, baseline functional status, comorbidities, type and
      duration of surgical procedure, and postoperative complications occurred in the
      index admission can predict risk of early readmission following LRYGB and LSG.

PMID- 26307599
TI  - Endoscopic mucosal resection of early oesophageal neoplasia in patients requiring
      anticoagulation: is it safe?
AB  - BACKGROUND AND AIM: Endoscopic mucosal resection (EMR) has become the standard
      treatment for early oesophageal neoplasia. The mucosal defect caused by EMR
      usually takes several weeks to heal. Despite guidelines on high-risk endoscopic
      procedures in patients on anticoagulation, evidence is lacking whether EMR is
      safe in such patients. We investigated the immediate and delayed bleeding risk in
      patients undergoing diagnostic or therapeutic oesophageal EMR comparing patients
      requiring warfarin anticoagulation with a control group. METHODS: Warfarin was
      stopped 5 days before the planned EMR and restarted on the evening following the
      procedure. Patients with high-risk conditions, such as recent pulmonary
      thromboemboli, received bridging with low molecular weight heparin. All EMRs were
      performed when the INR was <1.5. Bleeding events on the day of the EMR and within
      3 months post-procedure were documented. RESULTS: One hundred and seventeen
      consecutive patients with early oesophageal neoplasia were included. Sixty-eight
      EMRs were performed in 15 patients requiring anticoagulation. One patient on
      warfarin was readmitted 10 days after EMR with haematemesis and melaena. Out of
      400 EMRs in 102 controls, 26 immediate bleeding events occurred requiring
      endoscopic intervention. One delayed bleeding event (melaena) occurred in the
      control group. The number of bleeding events did not differ between groups [p =
      0.99; odds ratio 1.01 (0.30-3.44)], neither for acute (p = 0.76) nor delayed
      bleeding (p = 0.24). CONCLUSION: EMR of early oesophageal neoplasia can be safely
      performed in patients requiring anticoagulation when warfarin is discontinued 5
      days before the endoscopic intervention and reinstituted on the evening of the
      procedure day.

PMID- 26307600
TI  - Laparoscopic common bile duct exploration: 15-year experience in a district
      general hospital.
AB  - INTRODUCTION: The treatment of common bile duct (CBD) stones remains
      controversial with debate between endoscopic cholangiopancreatography (ERCP) and
      CBD exploration. A recent meta-analysis has shown no significant difference
      between these approaches; however, there is a trend in the literature to favour a
      single-stage procedure in the form of laparoscopic CBD exploration. We report our
      experience over a 15-year period. METHODS: All cases of CBD exploration were
      identified from 2000 to 2015 and analysed retrospectively from a large NHS
      Foundation Trust in Northumbria. There were no exclusions. The mean clinical
      follow-up was 6 months (range 3-36 months). RESULTS: A total of 296 patients were
      included who underwent laparoscopic CBD exploration: 203 were female and 93 were
      male. The mean age was 60 years (range 16-84 years). A total of 231 procedures
      were performed electively and 65 as an emergency. Ten procedures were
      successfully performed as day cases. Eleven procedures were converted to an open
      procedure due to adhesions or a difficult dissection (4 %). Sixty-three
      procedures were performed with a transcystic approach with a mean post-op stay of
      2 days (range 0-7). A total of 233 procedures were performed with a choledocotomy
      with a mean post-op stay of 6 days (range 3-14 days). Stone clearance was
      successful in 255 patients (86 %). Three patients died over the study period. Two
      were for medical complications and one for abdominal sepsis. Three patients
      returned to theatre for early post-operative bleeding (1 %). Sixteen patients had
      persistent bile leaks following a choledocotomy (6.8 %). No patients had a bile
      leak following transcystic exploration. Fourteen patients were followed up
      following failed stone removal. Nine had a successful ERCP, three had no stone
      seen on MRCP, and one patient required re-operation following a failed ERCP.
      CONCLUSIONS: Laparoscopic bile duct exploration can be performed successfully in
      both the emergency and elective settings. Day-case surgery is feasible in
      selected patients. A transcystic approach should be favoured where possible.

PMID- 26307601
TI  - Quantifying the relative irreplaceability of important bird and biodiversity
      areas.
AB  - World governments have committed to increase the global protected areas coverage
      by 2020, but the effectiveness of this commitment for protecting biodiversity
      depends on where new protected areas are located. Threshold- and complementarity
      based approaches have been independently used to identify important sites for
      biodiversity. We brought together these approaches by performing a
      complementarity-based analysis of irreplaceability in important bird and
      biodiversity areas (IBAs), which are sites identified using a threshold-based
      approach. We determined whether irreplaceability values are higher inside than
      outside IBAs and whether any observed difference depends on known characteristics
      of the IBAs. We focused on 3 regions with comprehensive IBA inventories and bird
      distribution atlases: Australia, southern Africa, and Europe. Irreplaceability
      values were significantly higher inside than outside IBAs, although differences
      were much smaller in Europe than elsewhere. Higher irreplaceability values in
      IBAs were associated with the presence and number of restricted-range species;
      number of criteria under which the site was identified; and mean geographic range
      size of the species for which the site was identified (trigger species). In
      addition, IBAs were characterized by higher irreplaceability values when using
      proportional species representation targets, rather than fixed targets. There
      were broadly comparable results when measuring irreplaceability for trigger
      species and when considering all bird species, which indicates a good surrogacy
      effect of the former. Recently, the International Union for Conservation of
      Nature has convened a consultation to consolidate global standards for the
      identification of key biodiversity areas (KBAs), building from existing
      approaches such as IBAs. Our results informed this consultation, and in
      particular a proposed irreplaceability criterion that will allow the new KBA
      standard to draw on the strengths of both threshold- and complementarity-based
      approaches. 

PMID- 26307602
TI  - Novel Radiotracer for ImmunoPET Imaging of PD-1 Checkpoint Expression on Tumor
      Infiltrating Lymphocytes.
AB  - Immune checkpoint signaling through the programmed death 1 (PD-1) axis to its
      ligand (PD-L1) significantly dampens anti-tumor immune responses. Cancer patients
      treated with checkpoint inhibitors that block this suppressive signaling have
      exhibited objective response rates of 20-40% for advanced solid tumors,
      lymphomas, and malignant melanomas. This represents a tremendous advance in
      cancer treatment. Unfortunately, all patients do not respond to immune checkpoint
      blockade. Recent findings suggest that patients with tumor infiltrating
      lymphocytes (TILs) expressing PD-1 may be most likely to respond to alphaPD-1/PD
      L1 checkpoint inhibitors. There is a compelling need for diagnostic and
      prognostic imaging tools to assess the PD-1 status of TILs in vivo. Here we have
      developed a novel immunoPET tracer to image PD-1 expressing TILs in a transgenic
      mouse model bearing melanoma. A (64)Cu labeled anti-mouse antibody (IgG) PD-1
      immuno positron emission tomography (PET) tracer was developed to detect PD-1
      expressing murine TILs. Quality control of the tracer showed >95% purity by HPLC
      and >70% immunoreactivity in an in vitro cell binding assay. ImmunoPET scans were
      performed over 1-48 h on Foxp3+.LuciDTR4 mice bearing B16-F10 melanoma tumors.
      Mice receiving anti-PD-1 tracer (200 +/- 10 MUCi/10-12 MUg/200 MUL) revealed high
      tracer uptake in lymphoid organs and tumors. BLI images of FoxP3(+) CD4(+) Tregs
      known to express PD-1 confirmed lymphocyte infiltration of tumors at the time of
      PET imaging. Biodistribution measurements performed at 48 h revealed a high (11*)
      tumor to muscle uptake ratio of the PET tracer (p < 0.05). PD-1 tumors exhibited
      7.4 +/- 0.7%ID/g tracer uptake and showed a 2* fold signal decrease when binding
      was blocked by unlabeled antibody. To the best of our knowledge this data is the
      first report to image PD-1 expression in living subjects with PET. This
      radiotracer has the potential to assess the prognostic value of PD-1 in
      preclinical models of immunotherapy and may ultimately aid in predicting response
      to therapies targeting immune checkpoints. 

PMID- 26307603
TI  - Comparison of the Pharmacokinetics and Pharmacodynamics of LY2963016 Insulin
      Glargine and EU- and US-Approved Versions of Lantus Insulin Glargine in Healthy
      Subjects: Three Randomized Euglycemic Clamp Studies.
AB  - OBJECTIVE: LY2963016 (LY IGlar) and Lantus (IGlar) are insulin glargine products
      manufactured by distinct processes but with identical amino acid sequences. Three
      studies evaluated the pharmacokinetic (PK) and pharmacodynamic (PD) similarity of
      LY IGlar and the European Union- and US-approved versions of IGlar. RESEARCH
      DESIGN AND METHODS: These were three single-site, randomized, double-blind, two
      treatment, four-period, crossover, euglycemic clamp studies. In each study,
      fasted healthy subjects received 0.5 units/kg s.c. doses of two different insulin
      glargine products on two occasions each, following a randomized sequence. A >=7
      day washout period separated the doses. Blood samples were collected predose and
      up to 24 h postdose to assess PK; PD was assessed by a euglycemic clamp lasting
      up to 24 h. RESULTS: A total of 211 subjects participated in the three studies.
      The PK (area under the curve [AUC]; maximum observed concentration [Cmax]) and PD
      (maximum glucose infusion rate [Rmax]; total glucose infusion during the clamp
      [Gtot]) were similar between LY IGlar and IGlar, with the ratios of geometric
      means ranging from 0.90 to 0.95 for PK parameters and from 0.91 to 0.99 for PD
      parameters across studies. In all cases, the 90% CIs for the ratios of geometric
      means were completely contained in the prespecified acceptance limits of 0.80
      1.25. Adverse events were similar between treatments. CONCLUSIONS: These studies
      demonstrated that the PK and PD properties of LY IGlar and IGlar were similar
      after single 0.5 units/kg s.c. doses in healthy subjects, contributing to the
      totality of evidence supporting similarity of these products.

PMID- 26307604
TI  - Effect of lipohypertrophy on accuracy of continuous glucose monitoring in
      patients with type 1 diabetes.

PMID- 26307605
TI  - Use of an alpha-Glucosidase Inhibitor and the Risk of Colorectal Cancer in
      Patients With Diabetes: A Nationwide, Population-Based Cohort Study.
AB  - OBJECTIVE: Acarbose, an alpha-glucosidase inhibitor, has been shown to have
      antineoplastic effects on colorectal cancer in biomarker studies. We assessed the
      association between acarbose use in patients with diabetes and incident
      colorectal cancer. RESEARCH DESIGN AND METHODS: We conducted a nationwide,
      population-based study using a large cohort with diabetes in the Taiwan National
      Health Insurance Research Database. Patients with newly diagnosed diabetes (n =
      1,343,484) were enrolled between 1998 and 2010. One control subject not using
      acarbose was randomly selected for each subject using acarbose after matching for
      age, sex, diabetes onset, and comorbidities. Cox proportional hazards regression
      with a competing risks analysis was used to calculate the hazard ratios (HRs) and
      95% CIs for the association between acarbose use and incident colorectal cancer
      for each eligible case-control pair (n = 199,296). RESULTS: There were 1,332
      incident cases of colorectal cancer in the cohort with diabetes during the follow
      up period of 1,487,136 person-years. The overall incidence rate was 89.6 cases
      per 100,000 person-years. Patients treated with acarbose had a 27% reduction in
      the risk of colorectal cancer compared with control subjects. The adjusted HRs
      were 0.73 (95% CI 0.63-0.83), 0.69 (0.59-0.82), and 0.46 (0.37-0.58) for patients
      using >0 to <90, 90 to 364, and >=365 cumulative defined daily doses of acarbose,
      respectively, compared with subjects who did not use acarbose (P for trend <
      0.001). CONCLUSIONS: Acarbose use reduced the risk of incident colorectal cancer
      in patients with diabetes in a dose-dependent manner.

PMID- 26307606
TI  - The relation between HbA1c and cardiovascular events in patients with type 2
      diabetes with and without vascular disease.
AB  - OBJECTIVE: Poor glycemic control is related to vascular events in patients with
      type 2 diabetes, but the presence of vascular disease might influence this
      relation. We evaluated the relation between glycemic control (HbA1c level) and
      new cardiovascular events and mortality in patients with type 2 diabetes, with
      and without vascular disease. RESEARCH DESIGN AND METHODS: In a cohort of 1,687
      patients with type 2 diabetes enrolled in the Second Manifestations of Arterial
      Disease (SMART) study, the continuous relation between HbA1c and cardiovascular
      events (composite of myocardial infarction, stroke, and vascular mortality) and
      all-cause mortality was evaluated with Cox proportional hazard analyses
      stratified for the presence of vascular disease. RESULTS: During a median follow
      up time of 6.1 years (interquartile range 3.1-9.5 years), a new cardiovascular
      event developed in 293 patients and 340 patients died. In all patients, the
      hazard ratio (HR) of the relation between HbA1c level and cardiovascular events
      was 1.06 (95% CI 0.97-1.17). A 1 percentage point higher HbA1c level was related
      to a 27% higher risk of a cardiovascular event in patients with type 2 diabetes
      without vascular disease (HR 1.27 [95% CI 1.06-1.51]), but not in patients with
      vascular disease (HR 1.03 [95% CI 0.93-1.15], P for interaction = 0.195). A 1
      percentage point higher HbA1c level was related to a 16% higher risk of death (HR
      1.16 [95% CI 1.06-1.28]) in patients with vascular disease and a nonsignificant
      13% higher risk of all-cause mortality (HR 1.13 [95% CI 0.97-1.31]) in patients
      without vascular disease. CONCLUSIONS: In patients with type 2 diabetes, there is
      a modest, but not statistically significant, relation between HbA1c level and
      cardiovascular events, and, as there was no statistically significant
      interaction, this relation was not different for patients with or without
      clinical manifestation of vascular disease.

PMID- 26307608
TI  - Body weight, metabolic dysfunction, and risk of type 2 diabetes in patients at
      high risk for cardiovascular events or with manifest cardiovascular disease: a
      cohort study.
AB  - OBJECTIVE: To quantify the role of BMI and metabolic dysfunction in the risk of
      development of type 2 diabetes in patients at high risk or with manifest vascular
      disease. RESEARCH DESIGN AND METHODS: A total of 6,997 patients participating in
      the prospective Secondary Manifestations of ARTerial disease (SMART) cohort study
      were classified according to BMI and metabolic dysfunction, defined as three or
      more of the modified National Cholesterol Education Program (NCEP) metabolic
      syndrome criteria (waist circumference replaced by hs-CRP >=2 mg/L). Risk of type
      2 diabetes (assessed with biannually questionnaires) was estimated with Cox
      proportional hazards analysis. RESULTS: During a median follow-up of 6.0 years
      (interquartile range 3.1-9.1 years), 519 patients developed type 2 diabetes
      (incidence rate 12/1,000 person-years). In the absence of metabolic dysfunction
      (<=2 NCEP criteria), adiposity increased the risk of type 2 diabetes compared
      with normal-weight patients (HR 2.5 [95% CI 1.5-4.2] for overweight and HR 4.3
      [95% CI 2.2-8.6] for obese patients). In the presence of metabolic dysfunction
      (>=3 NCEP criteria), an increased risk of type 2 diabetes was observed in
      patients with normal weight (HR 4.7 [95% CI 2.8-7.8]), overweight (HR 8.5 [95% CI
      5.5-13.4]), and obesity (HR 16.3 [95% CI 10.4-25.6]) compared with normal-weight
      patients without metabolic dysfunction. CONCLUSIONS: Adiposity, even in the
      absence of metabolic dysfunction, is a risk factor for type 2 diabetes. Moreover,
      presence of metabolic dysfunction increases the risk of type 2 diabetes in all
      BMI categories. This supports the assessment of adiposity and metabolic
      dysfunction in patients with vascular disease or at high risk for cardiovascular
      events.

PMID- 26307607
TI  - Potential Impact of Prescribing Metformin According to eGFR Rather Than Serum
      Creatinine.
AB  - OBJECTIVE: Many societies recommend using estimated glomerular filtration rate
      (eGFR) rather than serum creatinine (sCr) to determine metformin eligibility. We
      examined the potential impact of these recommendations on metformin eligibility
      among U.S. adults. RESEARCH DESIGN AND METHODS: Metformin eligibility was
      assessed among 3,902 adults with diabetes who participated in the 1999-2010
      National Health and Nutrition Examination Surveys and reported routine access to
      health care, using conventional sCr thresholds (eligible if <1.4 mg/dL for women
      and <1.5 mg/dL for men) and eGFR categories: likely safe, >=45 mL/min/1.73 m(2);
      contraindicated, <30 mL/min/1.73 m(2); and indeterminate, 30-44 mL/min/1.73
      m(2)). Different eGFR equations were used: four-variable MDRD, Chronic Kidney
      Disease Epidemiology Collaboration (CKD-EPI) creatinine (CKD-EPIcr), and CKD-EPI
      cystatin C, as well as Cockcroft-Gault (CG) to estimate creatinine clearance
      (CrCl). Diabetes was defined by self-report or A1C >=6.5% (48 mmol/mol). We used
      logistic regression to identify populations for whom metformin was likely safe
      adjusted for age, race/ethnicity, and sex. Results were weighted to the U.S.
      adult population. RESULTS: Among adults with sCr above conventional cutoffs, MDRD
      eGFR >=45 mL/min/1.73 m(2) was most common among men (adjusted odds ratio [aOR]
      33.3 [95% CI 7.4-151.5] vs. women) and non-Hispanic Blacks (aOR vs. whites 14.8
      [4.27-51.7]). No individuals with sCr below conventional cutoffs had an MDRD eGFR
      <30 mL/min/1.73 m(2). All estimating equations expanded the population of
      individuals for whom metformin is likely safe, ranging from 86,900 (CKD-EPIcr) to
      834,800 (CG). All equations identified larger populations with eGFR 30-44
      mL/min/1.73 m(2), for whom metformin safety is indeterminate, ranging from
      784,700 (CKD-EPIcr) to 1,636,000 (CG). CONCLUSIONS: The use of eGFR or CrCl to
      determine metformin eligibility instead of sCr can expand the adult population
      with diabetes for whom metformin is likely safe, particularly among non-Hispanic
      blacks and men.

PMID- 26307609
TI  - The development of executive function and language skills in the early school
      years.
AB  - BACKGROUND: The developmental relationships between executive functions (EF) and
      early language skills are unclear. This study explores the longitudinal
      relationships between children's early EF and language skills in a sample of
      children with a wide range of language abilities including children at risk of
      dyslexia. In addition, we investigated whether these skills independently predict
      children's attention/behaviour skills. METHOD: Data are presented from 243
      children at four time points. Children were selected for being at risk of reading
      difficulties either because of a family history of dyslexia (FR; N = 90) or
      because of concerns regarding their language development (LI; N = 79) or as
      typically developing controls (TD; N = 74). The children completed tasks to
      assess their executive function and language skills at ages 4, 5 and 6 years. At
      6 (T4) and 7 years (T5) parents and teachers rated the children's
      attention/behaviour skills. RESULTS: There was a strong concurrent relationship
      between language and EF at each assessment. Longitudinal analyses indicated a
      considerable degree of stability in children's language and EF skills: the
      influence of language on later EF skills (and vice versa) was weak and not
      significant in the current sample. Children's EF, but not language, skills at T3
      predicted attention/behaviour ratings at T4/T5. CONCLUSIONS: There is a strong
      concurrent association between language and EF skills during the preschool and
      early school years, when children with language impairment show persistent EF
      deficits. Latent variables measuring language and EF show high longitudinal
      stability with little evidence of significant or strong reciprocal influences
      between these constructs. EF, but not language, skills predict later ratings of
      children's attention and behaviour.

PMID- 26307610
TI  - Different Degrees of Iodine Deficiency Inhibit Differentiation of Cerebellar
      Granular Cells in Rat Offspring, via BMP-Smad1/5/8 Signaling.
AB  - Iodine deficiency (ID) during development results in dysfunction of the central
      nervous system (CNS) and affects psychomotor and motor function. It is worth
      noting that maternal mild and marginal ID tends to be the most common reason of
      preventable neurodevelopmental impairment, via a mechanism that has not been
      elucidated. Therefore, our aim was to study the effects of developmental mild and
      marginal ID on the differentiation of cerebellar granule cells (GCs) and
      investigate the activation of BMP-Smad1/5/8 signaling, which is crucial for the
      development and differentiation of cerebellum. Three developmental rat models
      were created by feeding dam rats with a diet deficient in iodine and deionized
      water supplemented with potassium iodide. Our results showed that different
      degrees of ID inhibited and delayed the differentiation of cerebellar GCs on
      postnatal day (PN) 7, PN14, and PN21. Moreover, mild and severe ID reduced the
      expression of BMP2 and p-Smad1/5/8, and increased the levels of Id2 on PN7, PN14,
      and PN21. However, marginal ID rarely altered expression of these proteins in the
      offspring. Our study supports the hypothesis that mild and severe ID during
      development inhibits the differentiation of cerebellar GCs, which may be ascribed
      to the down-regulation of BMP-Smad1/5/8 signaling and the overexpression of Id2.
      Furthermore, it was speculated that maternal marginal ID rarely affected the
      differentiation of cerebellar GCs in the offspring.

PMID- 26307611
TI  - microRNAs Modulate Spatial Memory in the Hippocampus and in the Ventral Striatum
      in a Region-Specific Manner.
AB  - MicroRNAs are endogenous, noncoding RNAs crucial for the post-transcriptional
      regulation of gene expression. Their role in spatial memory formation, however,
      is poorly explored. In this study, we analyzed learning-induced microRNA
      expression in the hippocampus and in the ventral striatum. Among miRNAs
      specifically downregulated by spatial training, we focused on the hippocampus
      specific miR-324-5p and the ventral striatum-specific miR-24. In vivo
      overexpression of the two miRNAs demonstrated that miR-324-5p is able to impair
      memory if administered in the hippocampus but not in the ventral striatum, while
      the opposite is true for miR-24. Overall, these findings demonstrate a causal
      relationship between miRNA expression changes and spatial memory formation.
      Furthermore, they provide support for a regional dissociation in the post
      transcriptional processes underlying spatial memory in the two brain structures
      analyzed.

PMID- 26307612
TI  - Expression Profile of MiR-128 in the Astrocytoma Patients and Cell Lines.
AB  - Malignant astrocytomas are the most common primary brain tumors. The critical
      characterizes of astrocyomas are their aggressive and infiltrative in the brain,
      which leads to uncontrollable by conventional forms of therapy. MicroRNAs are
      small RNAs that had been found to regulate their targets by specific binding to
      the 3'-untranslated region (3'UTR) of mRNA. Recent advances in understanding the
      molecular biology of these tumors have revealed that microRNA (miRNA) disruption
      may play important roles in the pathogenesis of astrocytomas. And some of the
      miRNA alterations were found in the serum of astrocytoma patients. In this study,
      we studied the expression profile of miR-128, in the different stages of
      astrocytoma tissues and two human astrocytoma cell lines, A172 and T98G cells. We
      found that the levels of miR-128 are decreased in the A172 and T98G cells when
      compared to normal human astrocyte (NHA). Furthermore, the levels of miR-128
      decreased gradually to the pathological stages of astrocytomas. We also
      identified that TROVE2 is a novel target of miR-128 by the luciferase reporter
      system. Furthermore, the expression levels of TROVE2 are dramatically increased
      with the pathological stages increasing. Finally, the levels of TROVE2 are
      negatively correlated with miR-128 in astrocytoma tissues. Our data provided
      novel evidence for the miR-128 and TROVE2 in the development of human
      astrocytomas.

PMID- 26307613
TI  - Digit ratio and autism spectrum disorders in the Avon Longitudinal Study of
      Parents and Children: a birth cohort study.
AB  - OBJECTIVES: To investigate whether second-to-fourth digit ratio (2D:4D), a
      measure commonly used as a proxy for fetal testosterone exposure, is associated
      with autism spectrum disorders (ASDs), as predicted by the extreme male brain
      theory of autism. DESIGN: A birth cohort study. SETTING: The Avon Longitudinal
      Study of Parents and Children (ALSPAC). PARTICIPANTS: 6015 ALSPAC children with
      data on digit ratio, at least 1 outcome measure and information on potential
      confounding variables (parental occupational class, maternal education and age at
      digit ratio measurement). Digit ratio was measured by the photocopy and calliper
      method. OUTCOMES: ASD diagnosis (cases were identified previously by record
      linkage or maternal report) and 4 measures that combine optimally within ALSPAC
      to predict ASD: the Children's Communication Checklist (coherence subscale), the
      Social and Communication Disorders Checklist, a repetitive behaviour measure, and
      the Emotionality, Activity and Sociability scale (sociability subscale). These
      measures were dichotomised, with approximately 10% defined as the 'risk' group.
      RESULTS: Using logistic regression, we examined the association of 2D:4D with
      ASDs and 4 dichotomised ASD traits. Covariates were occupational class, maternal
      education and age at 2D:4D measurement. 2D:4D was not associated with ASDs in
      males (adjusted OR per 1 SD increase in mean 2D:4D, 0.88 (95% CI 0.65 to 1.21),
      p=0.435) or females (adjusted OR=1.36 (95% CI 0.81 to 2.28), p=0.245). Similar
      results were observed after adjustment for IQ. There was 1 weak association
      between reduced coherence and increased left 2D:4D in males, in the opposite
      direction to that predicted by the extreme male brain theory (adjusted OR=1.15
      (95% CI 1.02 to 1.29), p=0.023). Given multiple comparisons, this is consistent
      with chance. CONCLUSIONS: In this population-based study, there was no strong
      evidence of an association between 2D:4D and ASD diagnosis or traits, although
      the CIs were wide. These results are not consistent with the extreme male brain
      theory.

PMID- 26307614
TI  - The outcome and cost-effectiveness of nurse-led care in the community for people
      with rheumatoid arthritis: a non-randomised pragmatic study.
AB  - OBJECTIVE: To determine the outcome and cost-effectiveness of nurse-led care in
      the community for people with rheumatoid arthritis (RA). DESIGN: Non-randomised
      pragmatic study. SETTING: Primary (7 primary care practices) and secondary care
      (single centre) in the UK. METHODS: In a single area, pragmatic non-randomised
      study, we assessed the outcome, cost-effectiveness of community-based nurse-led
      care (NLC) compared with rheumatologist-led outpatient care (RLC). Participants
      were 349 adults (70% female) with stable RA assessed at baseline, 6 and 12
      months. In the community NLC arm there were 192 participants. Outcome was
      assessed using Stanford Health Assessment Questionnaire (HAQ). The economic
      evaluation (healthcare perspective) estimated cost relative to change in HAQ and
      quality-adjusted life years (QALY) derived from EQ-5D-3L. We report complete case
      and multiple imputation results from regression analyses. RESULTS: The
      demographics and baseline characteristics of patients in the community group were
      comparable to those under hospital care apart from use of biological disease
      modifying antirheumatic drugs (DMARDS), which were adjusted for in the analysis.
      The mean incremental cost was estimated to be L224 less for RLC compared to the
      community NLC, with wide CIs (CI -L213 to L701, p=0.296). Levels of functional
      disability were not clinically significantly higher in the community NLC group:
      HAQ 0.096 (95% CI -0.026 to 0.206; p=0.169) and QALY 0.023 (95% CI -0.059 to
      0.012; p=0.194). CONCLUSIONS: The results suggest that community care may be
      associated with non-significant higher costs with no significant differences in
      clinical outcomes, and this suggests a low probability that it is cost-effective.

PMID- 26307615
TI  - Risk factors for maternal morbidity in Victoria, Australia: a population-based
      study.
AB  - OBJECTIVES: The aim of this analysis was to quantify the risk factors associated
      with maternal morbidity among women in Victoria, Australia, focusing particularly
      on sociodemographic factors. DESIGN: Case-control analysis. PARTICIPANTS: Data on
      all maternities in Victoria from 1 January 2006 to 31 December 2008. METHODS: A
      case-control analysis was conducted using unconditional logistic regression to
      calculate adjusted ORs (aORs). Cases were defined as all women noted to have had
      a severe complication during the index pregnancy. Severe maternal morbidity was
      defined by the validated, composite Australian Maternal Morbidity Outcome
      Indicator. Socioeconomic position was defined by Socio-Economic Indices for Areas
      (SEIFA), specifically the Index of Relative Socioeconomic Disadvantage (IRSD),
      and other variables analysed were age, parity, Indigenous background, multiple
      pregnancy, country of birth, coexisting medical condition, previous caesarean
      section, spontaneous abortion or ectopic pregnancy. RESULTS: The study population
      comprised 211,060 women, including 1119 cases of severe maternal morbidity
      (0.53%). Compared with the highest IRSD quintile, the aOR for the 2nd quintile
      was 1.23 (95% CI 1.03 to 1.49), 0.98 (95% CI 0.79 to 1.21) for the 3rd quintile,
      1.55 (95% CI 1.28 to 1.87) for the 4th and 1.21 (95% CI 1.00 to 1.47) for the
      lowest (most deprived) quintile. Indigenous status was associated with twice (aOR
      2.02; 95% CI 1.32 to 3.09) the odds of being a case. Other risk factors for
      severe maternal morbidity were age >= 35 years (aOR 1.22; 95% CI 1.04 to 1.44),
      coexisting medical condition (aOR 1.39; 95% CI 1.16 to 1.65), multiple pregnancy
      (aOR 2.30; 95% CI 1.71 to 3.10), primiparity (aOR 1.36; 95% CI 1.18 to 1.57),
      previous caesarean section (aOR 1.79; 95% CI 1.53 to 2.10) and previous
      spontaneous miscarriage (aOR 1.25; 95% CI 1.08 to 1.44). CONCLUSIONS: The
      findings from Victoria strongly suggest that social disadvantage needs to be
      acknowledged and further investigated as an independent risk factor for adverse
      maternal outcomes in Australia and incorporated into appropriate policy planning
      and healthcare programmes.

PMID- 26307616
TI  - The evaluation of an interactive web-based Pulmonary Rehabilitation programme:
      protocol for the WEB SPACE for COPD feasibility study.
AB  - INTRODUCTION: Pulmonary Rehabilitation (PR) is an evidence-based intervention
      that has been recommended in guidelines to be available to those who may benefit.
      However, not all patients with chronic obstructive pulmonary disease (COPD) have
      access to this service. Healthcare services have shown the need for the provision
      of PR in other forms to enable patient choice and service capacity. There is an
      increase in evidence for the use of the internet in the management of long-term
      conditions to provide education and promote self-management. The aim of this
      study is to see if an interactive web-based PR programme is a feasible
      alternative compared with conventional PR. METHODS AND ANALYSIS: This is a
      feasibility study designed to evaluate the efficacy of providing a web-based PR
      programme to improve patients exercise capacity, quality of life and promote self
      management in patients with moderate to severe COPD compared with conventional PR
      programmes. Eligible patients will be randomly allocated to receive either the
      web-based programme or conventional rehabilitation programme for 7 weeks using an
      internet-based randomisation system. Participants will be recruited from PR
      assessments, primary care and community rehabilitation programmes. Those
      randomised to the web-based programme work through the website which contains all
      the information that the patients receive in the PR classes. They receive weekly
      phone calls by a professional to help progress through the course on line. The
      outcome measures will be recruitment rates and eligibility as well as that
      standard for a PR assessment including measures of exercise capacity, quality of
      life questionnaires and physical activity. ETHICS AND DISSEMINATION: The research
      ethics committee for Northampton has provided ethical approval for the conduct of
      the study. The results of the study will be disseminated through appropriate
      conference presentations and peer reviewed journals. TRIAL REGISTRATION NUMBER:
      ISRCTN03142263.

PMID- 26307617
TI  - Why do patients with stroke not receive the recommended amount of active therapy
      (ReAcT)? Study protocol for a multisite case study investigation.
AB  - INTRODUCTION: Increased frequency and intensity of inpatient therapy contributes
      to improved outcomes for stroke survivors. Differences exist in the amount of
      therapy provided internationally. In England, Wales and Northern Ireland it is
      recommended that a minimum of 45 min of each active therapy should be provided at
      least 5 days a week provided the therapy is appropriate and that the patient can
      tolerate this. Sentinel Stroke National Audit Programme (2014) data demonstrate
      this standard is not being achieved for most patients. No research been
      undertaken to explore how therapists in England manage their practice to meet
      time-specific therapy recommendations. The ReAcT study aims to develop an in
      depth understanding of stroke therapy provision, including how the guideline of
      45 min a day of each relevant therapy, is interpreted and implemented by
      therapists, and how it is experienced by stroke-survivors and their families.
      METHODS AND ANALYSIS: A multisite ethnographic case study design in a minimum of
      six stroke units will include modified process mapping, observations of service
      organisation, therapy delivery and documentary analysis. Semistructured
      interviews with therapists and service managers (n=90), and with patients and
      informal carers (n=60 pairs) will be conducted. Data will be analysed using the
      Framework approach. ETHICS AND DISSEMINATION: The study received a favourable
      ethical opinion via the National Research Ethics Service (reference number:
      14/NW/0266). Participants will provide written informed consent or, where stroke
      survivors lack capacity, a consultee declaration will be sought. ReAcT is
      designed to generate insights into the organisational, professional, social,
      practical and patient-related factors acting as facilitators or barriers to
      providing the recommended amount of therapy. Provisional recommendations will be
      debated in consensus meetings with stakeholders who have not participated in
      ReAcT case studies or interviews. Final recommendations will be disseminated to
      therapists, service managers, clinical guideline developers and policymakers and
      stroke-survivors and informal carers.

PMID- 26307618
TI  - Development of a universal approach to increase physical activity among
      adolescents: the GoActive intervention.
AB  - OBJECTIVES: To develop a physical activity (PA) promotion intervention for
      adolescents using a process addressing gaps in the literature while considering
      participant engagement. We describe the initial development stages; (1) existing
      evidence, (2) large scale opinion gathering and (3) developmental qualitative
      work, aiming (A) to gain insight into how to increase PA among the whole of year
      9 (13-14 years-old) by identifying elements for intervention inclusion (B) to
      improve participant engagement and (C) to develop and refine programme design.
      METHODS: Relevant systematic reviews and longitudinal analyses of change were
      examined. An intervention was developed iteratively with older adolescents (17.3
      +/- 0.5 years) and teachers, using the following process: (1) focus groups with
      (A) adolescents (n=26) and (B) teachers (n=4); (2) individual interviews (n=5)
      with inactive and shy adolescents focusing on engagement and programme
      acceptability. Qualitative data were analysed thematically. RESULTS: Limitations
      of the existing literature include lack of evidence on whole population
      approaches, limited adolescent involvement in intervention development, and poor
      participant engagement. Qualitative work suggested six themes which may encourage
      adolescents to do more PA; choice, novelty, mentorship, competition, rewards and
      flexibility. Teachers discussed time pressures as a barrier to encouraging
      adolescent PA and suggested between-class competition as a strategy. GoActive
      aims to increase PA through increased peer support, self-efficacy, group
      cohesion, self-esteem and friendship quality, and is implemented in tutor groups
      using a student-led tiered-leadership system. CONCLUSIONS: We have followed an
      evidence-based iterative approach to translate existing evidence into an
      adolescent PA promotion intervention. Qualitative work with adolescents and
      teachers supported intervention design and addressed lack of engagement with
      health promotion programmes within this age group. Future work will examine the
      feasibility and effectiveness of GoActive to increase PA among adolescents while
      monitoring potential negative effects. The approach developed is applicable to
      other population groups and health behaviours. TRIAL REGISTRATION NUMBER:
      ISRCTN31583496.

PMID- 26307619
TI  - Supervision of care networks for frail community dwelling adults aged 75 years
      and older: protocol of a mixed methods study.
AB  - INTRODUCTION: The Dutch healthcare inspectorate (IGZ) supervises the quality and
      safety of healthcare in the Netherlands. Owing to the growing population of
      (community dwelling) older adults and changes in the Dutch healthcare system, the
      IGZ is exploring new methods to effectively supervise care networks that exist
      around frail older adults. The composition of these networks, where formal and
      informal care takes place, and the lack of guidelines and quality and risk
      indicators make supervision complicated in the current situation. METHODS AND
      ANALYSIS: This study consists of four phases. The first phase identifies risks
      for community dwelling frail older adults in the existing literature. In the
      second phase, a qualitative pilot study will be conducted to assess the needs and
      wishes of the frail older adults concerning care and well-being, perception of
      risks, and the composition of their networks, collaboration and coordination
      between care providers involved in the network. In the third phase,
      questionnaires based on the results of phase II will be sent to a larger group of
      frail older adults (n=200) and their care providers. The results will describe
      the composition of their care networks and prioritise risks concerning community
      dwelling older adults. Also, it will provide input for the development of a new
      supervision framework by the IGZ. During phase IV, a second questionnaire will be
      sent to the participants of phase III to establish changes of perception in risks
      and possible changes in the care networks. The framework will be tested by the
      IGZ in pilots, and the researchers will evaluate these pilots and provide
      feedback to the IGZ. ETHICS AND DISSEMINATION: The study protocol was approved by
      the Scientific Committee of the EMGO+institute and the Medical Ethical review
      committee of the VU University Medical Centre. Results will be presented in
      scientific articles and reports and at meetings.

PMID- 26307620
TI  - Children Learning About Secondhand Smoke (CLASS II): protocol of a pilot cluster
      randomised controlled trial.
AB  - INTRODUCTION: Exposure to secondhand smoke (SHS) increases children's risk of
      acquiring chest and ear infections, tuberculosis, meningitis and asthma. Smoking
      bans in public places (where implemented) have significantly reduced adults'
      exposure to SHS. However, for children, homes remain the most likely place for
      them to be exposed to SHS. Additional measures are therefore required to protect
      children from SHS. In a feasibility study in Dhaka, Bangladesh, we have shown
      that a school-based smoke-free intervention (SFI) was successful in encouraging
      children to negotiate and implement smoking restrictions in homes. We will now
      conduct a pilot trial to inform plans to undertake a cluster randomised
      controlled trial (RCT) investigating the effectiveness and cost-effectiveness of
      SFI in reducing children's exposure to SHS. METHODS AND ANALYSIS: We plan to
      recruit 12 primary schools in Dhaka, Bangladesh. From these schools, we will
      recruit approximately 360 schoolchildren in year 5 (10-12 years old), that is, 30
      per school. SFI consists of six interactive educational activities aimed at
      increasing pupils' knowledge about SHS and related harms, motivating them to act,
      providing skills to negotiate with adults to persuade them not to smoke inside
      homes and helping families to 'sign-up' to a voluntary contract to make their
      homes smoke-free. Children in the control arm will receive the usual education.
      We will estimate: recruitment and attrition rates, acceptability, fidelity to
      SFI, effect size, intracluster correlation coefficient, cost of intervention and
      adverse events. Our primary outcome will consist of SHS exposure in children
      measured by salivary cotinine. Secondary outcomes will include respiratory
      symptoms, lung function tests, healthcare contacts, school attendance, smoking
      uptake, quality of life and academic performance. ETHICS AND DISSEMINATION: The
      trial has received ethics approval from the Research Governance Committee at the
      University of York. Findings will help us plan for the definitive trial. TRIAL
      REGISTRATION NUMBER: ISRCTN68690577.

PMID- 26307621
TI  - Time-driven activity-based costing of multivessel coronary artery bypass grafting
      across national boundaries to identify improvement opportunities: study protocol.
AB  - INTRODUCTION: Coronary artery bypass graft (CABG) surgery is a well-established,
      commonly performed treatment for coronary artery disease--a disease that affects
      over 10% of US adults and is a major cause of morbidity and mortality. In 2005,
      the mean cost for a CABG procedure among Medicare beneficiaries in the USA was
      $32, 201 +/- $23,059. The same operation reportedly costs less than $2000 to
      produce in India. The goals of the proposed study are to (1) identify the
      difference in the costs incurred to perform CABG surgery by three Joint
      Commission accredited hospitals with reputations for high quality and efficiency
      and (2) characterise the opportunity to reduce the cost of performing CABG
      surgery. METHODS AND ANALYSIS: We use time-driven activity-based costing (TDABC)
      to quantify the hospitals' costs of producing elective, multivessel CABG. TDABC
      estimates the costs of a given clinical service by combining information about
      the process of patient care delivery (specifically, the time and quantity of
      labour and non-labour resources utilised to perform each activity) with the unit
      cost of each resource used to provide the care. Resource utilisation was
      estimated by constructing CABG process maps for each site based on observation of
      care and staff interviews. Unit costs were calculated as a capacity cost rate,
      measured as a $/min, for each resource consumed in CABG production. Multiplying
      together the unit costs and resource quantities and summing across all resources
      used will produce the average cost of CABG production at each site. We will
      conclude by conducting a variance analysis of labour costs to reveal
      opportunities to bend the cost curve for CABG production in the USA. ETHICS AND
      DISSEMINATION: All our methods were exempted from review by the Stanford
      Institutional Review Board. Results will be published in peer-reviewed journals
      and presented at scientific meetings.

PMID- 26307623
TI  - Pinpointing Melanoma's Invasive Trigger.

PMID- 26307622
TI  - Pre-exposure and postexposure prophylaxes and the combination HIV prevention
      methods (The Combine! Study): protocol for a pragmatic clinical trial at public
      healthcare clinics in Brazil.
AB  - INTRODUCTION: Few results from programmes based on combination prevention methods
      are available. We propose to analyse the degree of protection provided by
      postexposure prophylaxis (PEP) for consensual sexual activity at healthcare
      clinics, its compensatory effects on sexual behaviour; and the effectiveness of
      combination prevention methods and pre-exposure prophylaxis (PrEP), compared with
      exclusively using traditional methods. METHODS AND ANALYSIS: A total of 3200
      individuals aged 16 years or older presenting for PEP at 5 sexually transmitted
      disease (STD)/HIV clinics in 3 regions of Brazil will be allocated to one of two
      groups: the PEP group-individuals who come to the clinic within 72 h after a
      sexual exposure and start PEP; and the non-PEP group-individuals who come after
      72 h but within 30 days of exposure and do not start PEP. Clinical follow-up will
      be conducted initially for 6 months and comprise educational interventions based
      on information and counselling for using prevention methods, including PrEP. In
      the second study phase, individuals who remain HIV negative will be regrouped
      according to the reported use of prevention methods and observed for 18 months:
      only traditional methods; combined methods; and PrEP. Effectiveness will be
      analysed according to the incidence of HIV, syphilis and hepatitis B and C and
      protected sexual behaviour. A structured questionnaire will be administered to
      participants at baseline and every 6 months thereafter. Qualitative methods will
      be employed to provide a comprehensive understanding of PEP-seeking behaviour,
      preventive choices and exposure to HIV. ETHICS AND DISSEMINATION: This study will
      be conducted in accordance with the resolution of the School of Medicine Research
      Ethics Commission of Universidade de Sao Paulo (protocol no. 251/14). The
      databases will be available for specific studies, after management committee
      approval. Findings will be presented to researchers, health managers and civil
      society members by means of newspapers, electronic media and scientific journals
      and meetings.

PMID- 26307624
TI  - Skin Cancer Drug Also Targets Brain Tumors.

PMID- 26307625
TI  - PD-1 and PD-L1 Expression in Renal Cell Carcinoma with Sarcomatoid
      Differentiation.
AB  - Monoclonal antibodies that target the programmed death-1 (PD-1)-programmed death
      ligand-1 (PD-L1) axis have antitumor activity against multiple cancers. The
      presence of sarcomatoid differentiation in renal cell carcinoma (RCC) is
      associated with resistance to targeted therapy and poor responses to IL2
      immunotherapy. Given the aggressive nature of RCC with sarcomatoid
      differentiation and the exclusion of sarcomatoid histology from metastatic RCC
      clinical trials, less is understood regarding selection of therapies. Here, we
      characterized the PD-1/PD-L1 axis in RCC with sarcomatoid differentiation. We
      directly compared two PD-L1 antibodies and found concordance of PD-L1 positivity
      in 89% of tested RCCs with sarcomatoid differentiation. Coexpression of PD-L1 on
      neoplastic cells and the presence of PD-1-positive tumor-infiltrating lymphocytes
      were identified in 50% (13 of 26) of RCCs with sarcomatoid differentiation. In
      contrast, only 1 of 29 clear cell RCCs (3%) had concurrent expression of PD-L1
      and PD-1 (P = 0.002). Our study suggests that RCC with sarcomatoid
      differentiation may express PD-1/PD-L1 at a higher percentage than RCC without
      sarcomatoid differentiation, and patients with these tumors may be good
      candidates for treatment with anti-PD-1/PD-L1 therapies.

PMID- 26307626
TI  - Incidence, severity, mortality, and confounding factors for dissecting AAA
      detection in angiotensin II-infused mice: a meta-analysis.
AB  - AIMS: While angiotensin II-infused mice are the most popular model for
      preclinical aneurysm research, representative data on incidence, severity, and
      mortality of dissecting abdominal aortic aneurysms (AAAs) have never been
      established, and the influence of confounding factors is unknown. METHODS AND
      RESULTS: We performed a meta-analysis including 194 manuscripts representing 1679
      saline-infused, 4729 non-treated angiotensin II-infused, and 4057 treated
      angiotensin II-infused mice. Incidence (60%) and mortality (20%) rates are
      reported overall as well as for grade I (22%), grade II (26%), grade III (29%),
      and grade IV (24%) aneurysms. Dissecting AAA incidence was significantly (P <
      0.05) influenced by sex, age, genetic background, infusion time, and dose of
      angiotensin II. Mortality was influenced by sex, genetic background, and dose,
      but not by age or infusion time. Surprisingly, both incidence and mortality were
      significantly different (P < 0.05) when comparing angiotensin II-infused mice in
      descriptive studies (56% incidence and 19% mortality) with angiotensin II-infused
      mice that served as control animals in treatment studies designed to either
      enhance (35% incidence and 13% mortality) or reduce (73% incidence and 25%
      mortality) dissecting AAA formation. After stratification to account for
      confounding factors (selection bias), the observed effect was still present for
      incidence, but not for mortality. Possible underlying causes are detection bias
      (non-uniform definition for detection and quantification of dissecting AAA in
      mice) or publication bias (studies with negative results, related to incidence in
      the control group, not being published). CONCLUSIONS: Our data provide a new meta
      analysis-based reference for incidence and mortality of dissecting AAA in
      angiotensin II-infused mice, and indicate that treatment studies using this mouse
      model should be interpreted with caution.

PMID- 26307627
TI  - Reduced radiation dose for elective nodal irradiation in node-negative anal
      cancer: back to the roots?
AB  - BACKGROUND: Chemoradiation (CRT) is the standard of care in patients with node
      positive (cN+) and node-negative (cN0) anal cancer. Depending on the tumor size
      (T-stage), total doses of 50-60 Gray (Gy) in daily fractions of 1.8-2.0 Gy are
      usually applied to the tumor site. Inguinal and iliac lymph nodes usually receive
      a dose of >= 45 Gy. Since 2010, our policy has been to apply a reduced total dose
      of 39.6 Gy to uninvolved nodal regions. This paper provides preliminary results
      of the efficacy and safety of this protocol. PATIENTS AND METHODS: Overall, 30
      patients with histologically confirmed and node-negative anal cancer were treated
      in our department from 2009-2014 with definitive CRT. Histology all cases showed
      squamous cell carcinoma. A total dose of 39.6 Gy [single dose (SD) 1.8 Gy] was
      delivered to the iliac/inguinal lymph nodes. The area of the primary tumor
      received 50-59.4 Gy, depending on the T-stage. In parallel with the irradiation,
      5-fluorouracil (5-FU) at a dose of 1000 mg/m(2) was administered by continuous
      intravenous infusion over 24 h on days 1-4 and 29-32, and mitomycin C (MMC) at a
      dose of 10 mg/m(2) (maximum absolute dose 14 mg) was administered on days 1 and
      29. The distribution of the tumor stages was as follows: T1, n = 8; T2, n = 17;
      T3 n = 3. Overall survival (OS), local control (LC) of the lymph nodes, colostomy
      free survival (CFS), and acute and chronic toxicities were assessed. RESULTS: The
      median follow-up was 27.3 months (range 2.7-57.4 months). Three patients (10.0 %)
      died, 2 of cardiopulmonary diseases and one of liver failure, yielding a 3-year
      OS of 90.0 %. Two patients (6.7 %) relapsed early and received salvage
      colostomies, yielding a 3-year CFS of 93.3 %. No lymph node relapses were
      observed, giving a lymph node LC of 100 %. According to the Common Terminology
      Criteria for Adverse Events Version 4.0 (CTCAE V. 4.0), there were no grade IV
      gastrointestinal or genitourinary acute toxicities. Seven patients showed acute
      grade III perineal skin toxicity. Acute grade III groin skin toxicity was not
      observed. CONCLUSION: Reducing the total irradiation dose to uninvolved nodal
      regions to 39.6 Gy in chemoradiation protocols for anal carcinoma was safe and
      effective, and a prospective evaluation in future clinical trials is warranted.

PMID- 26307628
TI  - Stereotactic interstitial brachytherapy for the treatment of oligodendroglial
      brain tumors.
AB  - PURPOSE: We evaluated the treatment of oligodendroglial brain tumors with
      interstitial brachytherapy (IBT) using (125)iodine seeds ((125)I) and analyzed
      prognostic factors. PATIENTS AND METHODS: Between January 1991 and December 2010,
      63 patients (median age 43.3 years, range 20.8-63.4 years) suffering from
      oligodendroglial brain tumors were treated with (125)I IBT either as primary,
      adjuvantly after incomplete resection, or as salvage therapy after tumor
      recurrence. Possible prognostic factors influencing disease progression and
      survival were retrospectively investigated. RESULTS: The actuarial 2-, 5-, and 10
      year overall and progression-free survival rates after IBT for WHO II tumors were
      96.9, 96.9, 89.8 % and 96.9, 93.8, 47.3 %; for WHO III tumors 90.3, 77, 54.9 %
      and 80.6, 58.4, 45.9 %, respectively. Magnetic resonance imaging demonstrated
      complete remission in 2 patients, partial remission in 13 patients, stable
      disease in 17 patients and tumor progression in 31 patients. Median time to
      progression for WHO II tumors was 87.6 months and for WHO III tumors 27.8 months.
      Neurological status improved in 10 patients and remained stable in 20 patients,
      while 9 patients deteriorated. There was no treatment-related mortality.
      Treatment-related morbidity was transient in 11 patients. WHO II, KPS >= 90 %,
      frontal location, and tumor surface dose > 50 Gy were associated with increased
      overall survival (p <= 0.05). Oligodendroglioma and frontal location were
      associated with a prolonged progression-free survival (p <= 0.05). CONCLUSION:
      Our study indicates that IBT achieves local control rates comparable to surgery
      and radio-/chemotherapy treatment, is minimally invasive, and safe. Due to the
      low rate of side effects, IBT may represent an attractive option as part of a
      multimodal treatment schedule, being supplementary to microsurgery or as a
      salvage therapy after chemotherapy and conventional irradiation.

PMID- 26307629
TI  - [Errors in medicine. Causes, impact and improvement measures to improve patient
      safety].
AB  - The guarantee of quality of care and patient safety is of major importance in
      hospitals even though increased economic pressure and work intensification are
      ubiquitously present. Nevertheless, adverse events still occur in 3-4 % of
      hospital stays and of these 25-50 % are estimated to be avoidable. The
      identification of possible causes of error and the development of measures for
      the prevention of medical errors are essential for patient safety. The
      implementation and continuous development of a constructive culture of error
      tolerance are fundamental.The origins of errors can be differentiated into
      systemic latent and individual active causes and components of both categories
      are typically involved when an error occurs. Systemic causes are, for example out
      of date structural environments, lack of clinical standards and low personnel
      density. These causes arise far away from the patient, e.g. management decisions
      and can remain unrecognized for a long time. Individual causes involve, e.g.
      confirmation bias, error of fixation and prospective memory failure. These causes
      have a direct impact on patient care and can result in immediate injury to
      patients. Stress, unclear information, complex systems and a lack of professional
      experience can promote individual causes. Awareness of possible causes of error
      is a fundamental precondition to establishing appropriate countermeasures.Error
      prevention should include actions directly affecting the causes of error and
      includes checklists and standard operating procedures (SOP) to avoid fixation and
      prospective memory failure and team resource management to improve communication
      and the generation of collective mental models. Critical incident reporting
      systems (CIRS) provide the opportunity to learn from previous incidents without
      resulting in injury to patients. Information technology (IT) support systems,
      such as the computerized physician order entry system, assist in the prevention
      of medication errors by providing information on dosage, pharmacological
      interactions, side effects and contraindications of medications.The major
      challenges for quality and risk management, for the heads of departments and the
      executive board is the implementation and support of the described actions and a
      sustained guidance of the staff involved in the modification management process.
      The global trigger tool is suitable for improving transparency and objectifying
      the frequency of medical errors. 

PMID- 26307630
TI  - [Personnel marketing in anesthesiology. Perception, use and evaluation by the
      target group].
AB  - BACKGROUND: The human resources situation in the healthcare system is
      characterized by a manpower shortage. Recruiting medical staff is of great
      importance for hospitals and particularly in anesthesiology. Approaching and
      recruiting staff usually happens through external personnel marketing (PM);
      however, up until now the efficacy of these PM measures has barely been
      empirically investigated. AIM: The goal of this empirical study was to examine
      how familiar hospital physicians at varying career levels are with the different
      tools employed by external PM and how frequently they used as well as rated these
      tools in terms of benefits. Based on this information, the preferences of medical
      staff with respect to detailing the workplace of "hospital physician" as well as
      factors of the hospital's attractiveness as an employer were evaluated. Another
      aim was to derive recommendations on how to optimize the marketing instruments
      used for external PM in the healthcare system. MATERIAL AND METHODS: In an
      internet-based survey, 154 female and male physicians were questioned about their
      knowledge, use and benefit assessment of a total of 43 PM tools. RESULTS:
      Conventional methods of addressing applicants were commonly used but ranked
      behind the more personal and direct targeting tools in terms of benefit
      assessments. Internet-based tools with a conceptual affinity to conventional
      methods were also highly rated in terms of benefits. In contrast, unconventional
      methods of addressing applicants were hardly known and were not viewed as being
      useful. The PM tools from the field of "overall conditions for cooperation in the
      company" mainly received high to very high benefit assessments. These referred
      primarily to non-monetary factors, human resource development measures and also
      to aspects of remuneration. Image-promoting PM tools were rarely assessed as
      being useful, with the exception of measures aimed at creating personal contact
      between the hospital or unit/department and applicants or those allowing personal
      insight into the department's range of activities. The correlation between
      familiarity with PM tools and positive benefit assessments was low. CONCLUSION:
      The results of this PM study can contribute to the development of an effective
      and efficient conception of PM measures by hospitals. Addressing applicants
      through traditional job and internet-based advertisements should be supplemented
      by personalized targeting of potential applicants and innovative targeting
      instruments must be systematically developed and promoted in order to become
      effective. It remains questionable whether the target group of external PM can be
      reached with exclusively or even predominantly image-cultivating measures on
      behalf of the healthcare company, such as image campaigns. The most effective PM
      tools create good working conditions and develop factors contributing to the
      employer's attractiveness. These two tools should be given priority in human
      resource development also taking material incentives into consideration, all of
      which support the effective set-up of an employer branding.

PMID- 26307631
TI  - [Fractures of the thoracic and lumbar spine].
AB  - Fractures of the thoracic and lumbar spine result from high velocity trauma,
      assuming bone density is normal. The main location of fractures is the
      thoracolumbar junction. Most injuries can be treated conservatively; however,
      patients transferred to hospitals and spine centers represent a preselection with
      more severe trauma and a higher incidence of operative treatment. There is a
      large variety of operative techniques that can be used, which can be principally
      differentiated by the approach: posterior or anterior. Dorsal approaches are
      differentiated by the instrumentation for spondylodesis as open or percutaneous
      techniques. Minimally invasive options are favored more and more. For
      osteoporotic bone, cement augmented solutions may be used. Correct reduction of
      mainly kyphotic malalignment is crucial for the long-term outcome.
      Biomechanically stable reconstruction of the anterior spinal column is important
      mainly for the thoracolumbar junction. 

PMID- 26307632
TI  - [Multiple contact sensitization].
AB  - Contact allergy to several non-related haptens, usually termed polysensitization
      (PS), is often used to characterize patients who are particularly prone to
      sensitization. A conventional definition for PS is positive reactions to three or
      more haptens of the baseline series, e.g., the baseline series of the German
      Contact Dermatitis Research Group. Previous genetic as well as epidemiological
      studies have already indicated a number of potential risk factors for PS. In this
      context, both endogenous as well as exogenousfactors appear to be crucial. The
      former comprise polymorphism of IL-16 and TNF coding genes, the latter mostly
      occupational exposure, which often entails intense and repeated skin contact to a
      set of more or less characteristic contact allergens. Moreover, age and sex are
      related both with contact allergy to certain substances and with PS, as is the
      anatomical site of contact dermatitis. The degree to which contact allergy to a
      specific hapten is associated with PS, i.e., with contact allergy to several
      other haptens, varies greatly. 

PMID- 26307634
TI  - Incomplete penetrance of CD46 mutation causing familial atypical hemolytic uremic
      syndrome.
AB  - BACKGROUND: Hemolytic uremic syndrome (HUS) secondary to homozygous mutations in
      CD46 is uncommon. While heterozygous individuals may remain asymptomatic,
      homozygous mutations with severely depleted CD46 surface expression without
      disease manifestation is rare. METHODS: We report on two siblings with features
      suggestive of hemolytic uremic syndrome. Estimation of CD46 expression by flow
      cytometry and gene sequencing were performed in members of this family. RESULTS:
      Three siblings, two of whom were symptomatic, had markedly decreased (<10%) cell
      surface expression of CD46 and homozygous splice site mutation (IVS2 + 2 T > G)
      in the CD46 gene; the other 10-year-old sibling was asymptomatic. The illness was
      preceded by dengue shock syndrome in the index case. Both parents and two other
      siblings were heterozygous for this CD46 mutation. CONCLUSIONS: Homozygous IVS2 +
      2 T > G mutation in CD46 gene, similar to heterozygous mutation, may be
      clinically silent at least during childhood. The role of antecedent infections in
      triggering the disease requires further examination.

PMID- 26307633
TI  - Acetazolamide sensitive tissue calcification and aging of klotho-hypomorphic
      mice.
AB  - Klotho, a protein expressed mainly in the kidney, is required for the inhibitory
      effect of FGF23 on renal 1,25(OH)2D3 formation. Klotho counteracts vascular
      calcification and diverse age-related disorders. Klotho-hypomorphic mice (kl/kl)
      suffer from severe vascular calcification and rapid aging. The calcification is
      at least in part caused by excessive 1,25(OH)2D3, Ca(2+), and phosphate
      concentrations in blood, which trigger osteogenic signaling including
      upregulation of alkaline phosphatase (Alpl). As precipitation of calcium and
      phosphate is fostered by alkaline pH, extracellular acidosis could counteract
      tissue calcification. In order to induce acidosis, acetazolamide was added to
      drinking water (0.8 g/l) of kl/kl and wild-type mice. As a result, acetazolamide
      treatment of kl/kl mice partially reversed the growth deficit, tripled the life
      span, almost completely reversed the calcifications in trachea, lung, kidney,
      stomach, intestine, and vascular tissues, the excessive aortic alkaline
      phosphatase mRNA levels and the plasma concentrations of osteoprotegerin,
      osteopontin as well as fetuin-A, without significantly decreasing FGF23,
      1,25(OH)2D3, Ca(2+), and phosphate plasma concentrations. In primary human aortic
      smooth muscle cells, acidotic environment prevented phosphate-induced alkaline
      phosphatase mRNA expression. The present study reveals a completely novel effect
      of acetazolamide, i.e., interference with osteoinductive signaling and tissue
      calcification in kl/kl mice. KEY MESSAGES: Klotho deficient (kl/kl) mice suffer
      from hyperphosphatemia with dramatic tissue calcification. Acetazolamide (ACM)
      treatment partially reversed the growth deficit of kl/kl mice. In kl/kl mice, ACM
      reversed tissue calcification despite continued hyperphosphatemia. ACM tripled
      the life span of kl/kl mice. In human aortic smooth muscle cells, low
      extracellular pH prevented osteogenic signaling.

PMID- 26307635
TI  - Prevalence and correlates of 25-hydroxyvitamin D deficiency in the Chronic Kidney
      Disease in Children (CKiD) cohort.
AB  - BACKGROUND: Vitamin D plays an important role in the mineral and bone disorder
      seen in chronic kidney disease (CKD). Deficiency of 25-hydroxyvitamin D (25OHD)
      is highly prevalent in the adult CKD population. METHODS: The prevalence and
      determinants of 25OHD deficiency (defined as a level <20 ng/ml) were examined
      longitudinally in 506 children in the CKiD cohort. Predictors of secondary
      hyperparathyroidism and the determinants of 1,25-dihydroxyvitamin D (1,25(OH)2D)
      levels were also evaluated. RESULTS: Deficiency of 25OHD was observed in 28 % of
      the cohort at enrollment. Significant predictors of 25OHD deficiency were older
      age, non-white race, higher body mass index, assessment during winter, less often
      than daily milk intake, non-use of nutritional vitamin D supplement and
      proteinuria. Lower values of glomerular filtration rate (GFR), serum 25OHD,
      calcium and higher levels of FGF23 were significant determinants of secondary
      hyperparathyroidism. Lower GFR, low serum 25OHD, nephrotic-range proteinuria, and
      high FGF23 levels were significant determinants of serum 1,25(OH)2 D levels.
      CONCLUSIONS: Deficiency of 25OHD is prevalent in children with CKD and is
      associated with potentially modifiable risk factors such as milk intake,
      nutritional vitamin D supplement use, and proteinuria. 25OHD deficiency is a risk
      factor for secondary hyperparathyroidism and decreased serum 1,25(OH)2D in
      children with CKD.

PMID- 26307636
TI  - Replication-Competent Influenza Virus and Respiratory Syncytial Virus Luciferase
      Reporter Strains Engineered for Co-Infections Identify Antiviral Compounds in
      Combination Screens.
AB  - Myxoviruses such as influenza A virus (IAV) and respiratory syncytial virus (RSV)
      are major human pathogens, mandating the development of novel therapeutics. To
      establish a high-throughput screening protocol for the simultaneous
      identification of pathogen- and host-targeted hit candidates against either
      pathogen or both, we have attempted co-infection of cells with IAV and RSV.
      However, viral replication kinetics were incompatible, RSV signal window was low,
      and an IAV-driven minireplicon reporter assay used in initial screens narrowed
      the host cell range and restricted the assay to single-cycle infections. To
      overcome these limitations, we developed an RSV strain carrying firefly
      luciferase fused to an innovative universal small-molecule assisted shut-off
      domain, which boosted assay signal window, and a hyperactive fusion protein that
      synchronized IAV and RSV reporter expression kinetics and suppressed the
      identification of RSV entry inhibitors sensitive to a recently reported RSV pan
      resistance mechanism. Combined with a replication-competent recombinant IAV
      strain harboring nanoluciferase, the assay performed well on a human respiratory
      cell line and supports multicycle infections. Miniaturized to 384-well format,
      the protocol was validated through screening of a set of the National Institutes
      of Health Clinical Collection (NCC) in quadruplicate. These test screens
      demonstrated favorable assay parameters and reproducibility. Application to a
      LOPAC library of bioactive compounds in a proof-of-concept campaign detected
      licensed antimyxovirus therapeutics, ribavirin and the neuraminidase inhibitor
      zanamivir, and identified two unexpected RSV-specific hit candidates, Fenretinide
      and the opioid receptor antagonist BNTX-7. Hits were evaluated in direct and
      orthogonal dose-response counterscreens using a standard recRSV reporter strain
      expressing Renilla luciferase. 

PMID- 26307637
TI  - Winter circulation weather types and hospital admissions for respiratory diseases
      in Galicia, Spain.
AB  - The link between various pathologies and atmospheric conditions has been a
      constant topic of study over recent decades in many places across the world;
      knowing more about it enables us to pre-empt the worsening of certain diseases,
      thereby optimizing medical resources. This study looked specifically at the
      connections in winter between respiratory diseases and types of atmospheric
      weather conditions (Circulation Weather Types, CWT) in Galicia, a region in the
      north-western corner of the Iberian Peninsula. To do this, the study used
      hospital admission data associated with these pathologies as well as an automatic
      classification of weather types. The main result obtained was that weather types
      giving rise to an increase in admissions due to these diseases are those
      associated with cold, dry weather, such as those in the east and south-east, or
      anticyclonic types. A second peak was associated with humid, hotter weather,
      generally linked to south-west weather types. In the future, this result may help
      to forecast the increase in respiratory pathologies in the region some days in
      advance.

PMID- 26307639
TI  - Review: advances in in situ and satellite phenological observations in Japan.
AB  - To accurately evaluate the responses of spatial and temporal variation of
      ecosystem functioning (evapotranspiration and photosynthesis) and services
      (regulating and cultural services) to the rapid changes caused by global warming,
      we depend on long-term, continuous, near-surface, and satellite remote sensing of
      phenology over wide areas. Here, we review such phenological studies in Japan and
      discuss our current knowledge, problems, and future developments. In contrast
      with North America and Europe, Japan has been able to evaluate plant phenology
      along vertical and horizontal gradients within a narrow area because of the
      country's high topographic relief. Phenological observation networks that support
      scientific studies and outreach activities have used near-surface tools such as
      digital cameras and spectral radiometers. Differences in phenology among
      ecosystems and tree species have been detected by analyzing the seasonal
      variation of red, green, and blue digital numbers (RGB values) extracted from
      phenological images, as well as spectral reflectance and vegetation indices. The
      relationships between seasonal variations in RGB-derived indices or spectral
      characteristics and the ecological and CO2 flux measurement data have been well
      validated. In contrast, insufficient satellite remote-sensing observations have
      been conducted because of the coarse spatial resolution of previous datasets,
      which could not detect the heterogeneous plant phenology that results from
      Japan's complex topography and vegetation. To improve Japanese phenological
      observations, multidisciplinary analysis and evaluation will be needed to link
      traditional phenological observations with "index trees," near-surface and
      satellite remote-sensing observations, "citizen science" (observations by
      citizens), and results published on the Internet. 

PMID- 26307640
TI  - Excitonic Relaxation and Coherent Vibrational Dynamics in Zinc Chlorin Aggregates
      for Artificial Photosynthetic Systems.
AB  - The excitonic relaxation and coherent vibrational dynamics in stairlike zinc
      chlorin aggregates prepared for mimicking chlorosome in nature have been studied
      simultaneously by 6.8 fs real-time vibrational laser spectroscopy. The relaxation
      from Q-exciton state to the dark nonfluorescent charge-transfer (CT) state is
      determined to be 850 +/- 70 fs. The spectral distribution of the molecular
      vibrational amplitude has been discussed in terms of the difference in the
      equilibrium positions of potential curves between the ground state and the
      excited state. Since the displacement in the coordinate space from the potential
      minimum of the ground state to that of the excited states is small, coherent
      oscillations generated by the impulsive excitation are strongest where the slope
      of the excitonic resonance is largest. Consequently, the probe wavelength
      dependence of the amplitude modulation follows the first derivative of the
      excitonic resonance, and pi phase jump has been observed. Excitonic transition
      energy modulation caused by the coherent molecular vibrations has also been
      studied, and the vibrational mode with a low frequency of 146 cm(-1) is found to
      play a dominating role in the transition energy shift effect. 

PMID- 26307638
TI  - Suppression of nighttime sap flux with lower stem photosynthesis in Eucalyptus
      trees.
AB  - It is widely accepted that substantial nighttime sap flux (J s,n) or
      transpiration (E) occurs in most plants, but the physiological implications are
      poorly known. It has been hypothesized that J s,n or E serves to enhance nitrogen
      uptake or deliver oxygen; however, no clear evidence is currently available. In
      this study, sap flux (J s) in Eucalyptus grandis * urophylla with apparent stem
      photosynthesis was measured, including control trees which were covered by
      aluminum foil (approximately 1/3 of tree height) to block stem photosynthesis. We
      hypothesized that the nighttime water flux would be suppressed in trees with
      lower stem photosynthesis. The results showed that the green tissue degraded
      after 3 months, demonstrating a decrease in stem photosynthesis. The daytime J s
      decreased by 21.47%, while J s,n decreased by 12.03% in covered trees as compared
      to that of control, and the difference was statistically significant (P < 0.01).
      The linear quantile regression model showed that J s,n decreased for a given
      daytime transpiration water loss, indicating that J s,n was suppressed by lower
      stem photosynthesis in covered trees. Predawn (psi pd) of covered trees was
      marginally higher than that of control while lower at predawn stomatal
      conductance (g s), indicating a suppressed water flux in covered trees. There was
      no difference in leaf carbon content and delta(13)C between the two groups, while
      leaf nitrogen content and delta(15)N were significantly higher in covered trees
      than that of the control (P < 0.05), indicating that J s,n was not used for
      nitrogen uptake. These results suggest that J s,n may act as an oxygen pathway
      since green tissue has a higher respiration or oxygen demand than non-green
      tissue. Thus, this study demonstrated the physiological implications of J s,n and
      the possible benefits of nighttime water use or E by the tree.

PMID- 26307642
TI  - New Insights Into Nonadherence With Adjuvant Endocrine Therapy Among Young Women
      With Breast Cancer.

PMID- 26307641
TI  - Impact of Fertility Concerns on Tamoxifen Initiation and Persistence.
AB  - BACKGROUND: Adjuvant tamoxifen reduces breast cancer recurrence risk and
      mortality; however, initiation and treatment persistence are poor for younger
      patients. We hypothesized that a unique set of factors, including fertility
      concerns, would contribute to the poor tamoxifen use among premenopausal
      patients. METHODS: From 2007 to 2012, 515 premenopausal patients younger than age
      45 years, with stage 0 to III hormone receptor-positive breast cancer, for whom
      tamoxifen was recommended, were identified. Clinical and pathologic tumor
      characteristics, treatment regimens, and fertility concerns were recorded.
      Clinical factors associated with tamoxifen noninitiation and discontinuation were
      identified using univariate and multivariable analysis. After the recommendation
      for tamoxifen, patient reasons for tamoxifen noninitiation or discontinuation
      were also documented. All statistical tests were two-sided. RESULTS: Based on
      multivariable analysis, fertility concerns were statistically associated with
      both noninitiation (odds ratio = 5.04, 95% confidence interval (CI) = 2.29 to
      11.07) and early discontinuation (hazard ratio = 1.78, 95% CI = 1.09 to 3.38) of
      tamoxifen. Other independent predictors of noninitiation included a diagnosis of
      ductal carcinoma in situ, declining radiation, and not receiving chemotherapy
      (stage I-III). Additionally, smoking and not receiving radiation therapy were
      statistically significant predictors of early withdrawal from therapy. Primary
      patient reasons for noninitiation and early discontinuation included concerns
      about side effects and fertility. CONCLUSION: This study provided insight into
      factors associated with tamoxifen use for reproductive-aged breast cancer
      survivors, with a new focus on fertility. Fertility concerns negatively impacted
      tamoxifen initiation and continuation among premenopausal patients. Interventions
      to optimize treatment initiation and persistence for young cancer patients should
      include access to fertility preservation options.

PMID- 26307643
TI  - The impact of the National Institute for Health Research Health Technology
      Assessment programme, 2003-13: a multimethod evaluation.
AB  - BACKGROUND: The National Institute for Health Research (NIHR) Health Technology
      Assessment (HTA) programme supports research tailored to the needs of NHS
      decision-makers, patients and clinicians. This study reviewed the impact of the
      programme, from 2003 to 2013, on health, clinical practice, health policy, the
      economy and academia. It also considered how HTA could maintain and increase its
      impact. METHODS: Interviews (n = 20): senior stakeholders from academia, policy
      making organisations and the HTA programme. Bibliometric analysis: citation
      analysis of publications arising from HTA programme-funded research. Researchfish
      survey: electronic survey of all HTA grant holders. Payback case studies (n =
      12): in-depth case studies of HTA programme-funded research. RESULTS: We make the
      following observations about the impact, and routes to impact, of the HTA
      programme: it has had an impact on patients, primarily through changes in
      guidelines, but also directly (e.g. changing clinical practice); it has had an
      impact on UK health policy, through providing high-quality scientific evidence -
      its close relationships with the National Institute for Health and Care
      Excellence (NICE) and the National Screening Committee (NSC) contributed to the
      observed impact on health policy, although in some instances other organisations
      may better facilitate impact; HTA research is used outside the UK by other HTA
      organisations and systematic reviewers - the programme has an impact on HTA
      practice internationally as a leader in HTA research methods and the funding of
      HTA research; the work of the programme is of high academic quality - the Health
      Technology Assessment journal ensures that the vast majority of HTA programme
      funded research is published in full, while the HTA programme still encourages
      publication in other peer-reviewed journals; academics agree that the programme
      has played an important role in building and retaining HTA research capacity in
      the UK; the HTA programme has played a role in increasing the focus on
      effectiveness and cost-effectiveness in medicine - it has also contributed to
      increasingly positive attitudes towards HTA research both within the research
      community and the NHS; and the HTA focuses resources on research that is of value
      to patients and the UK NHS, which would not otherwise be funded (e.g. where there
      is no commercial incentive to undertake research). The programme should consider
      the following to maintain and increase its impact: providing targeted support for
      dissemination, focusing resources when important results are unlikely to be
      implemented by other stakeholders, particularly when findings challenge vested
      interests; maintaining close relationships with NICE and the NSC, but also
      considering other potential users of HTA research; maintaining flexibility and
      good relationships with researchers, giving particular consideration to the
      Technology Assessment Report (TAR) programme and the potential for learning
      between TAR centres; maintaining the academic quality of the work and the focus
      on NHS need; considering funding research on the short-term costs of the
      implementation of new health technologies; improving the monitoring and
      evaluation of whether or not patient and public involvement influences research;
      improve the transparency of the priority-setting process; and continuing to
      monitor the impact and value of the programme to inform its future scientific and
      administrative development.

PMID- 26307645
TI  - Treatment of post-traumatic carotid-cavernous fistulas using pipeline
      embolization device assistance.
AB  - This report describes two cases of post-traumatic, high flow carotid-cavernous
      fistulas that demonstrated residual shunting after initial embolization with
      coils and Onyx, and that were successfully closed with pipeline embolization
      devices. Following their combined endovascular treatments, the patients
      experienced clinical improvement of symptoms with durable obliteration of the
      fistulous communications. 

PMID- 26307644
TI  - Relation of Cardiometabolic Risk Factors between Parents and Children.
AB  - OBJECTIVES: To explore the relations of parent-child cardiometabolic risk factors
      and assess the influence of adiposity on these associations. STUDY DESIGN:
      Associations of adiposity, blood pressure (BP), lipids, fasting insulin and
      glucose, and a risk factor cluster score (CS) were evaluated in a cross-sectional
      study of 179 parents and their children (6-18 years, N = 255). Insulin resistance
      was assessed by euglycemic clamp in parents and children aged 10 years or older.
      Metabolic syndrome in parents was defined by National Cholesterol Education
      Program's Adult Treatment Panel III criteria. CSs of the risk factors were
      created based on age-specific z-scores. Analyses included Pearson correlation and
      linear regression, adjusted for parent and child age, sex, race, and body mass
      index (BMI), accounting for within-family correlation. RESULTS: We found positive
      parent-child correlations for measures of adiposity (BMI, BMI percentile, waist,
      subcutaneous fat, and visceral fat; r = 0.22-0.34, all P <= .003), systolic BP (r
      = 0.20, P = .002), total cholesterol (r = 0.39, P < .001), low-density
      lipoprotein cholesterol (r = 0.34, P < .001), high density lipoprotein
      cholesterol (r = 0.26, P < .001), triglycerides (r = 0.19, P = .01), and insulin
      sensitivity (r = 0.22, P = .02) as well as CSs (r = 0.15, P = .02). After
      adjustment for BMI all parent-child correlations, except systolic BP, remained
      significant. CONCLUSIONS: Although adiposity is strongly correlated between
      parents and children, many cardiometabolic risk factors correlate independent of
      parent and child BMI. Adverse parental cardiometabolic profiles may identify at
      risk children independent of the child's adiposity status.

PMID- 26307646
TI  - Chronic recurrent multifocal osteomyelitis: a rare skeletal disorder.
AB  - Chronic recurrent multifocal osteomyelitis (CRMO) is a rare non-infectious
      inflammatory bone disease of unknown aetiology. CRMO mainly affects the
      metaphyses of long bones and spine in children and young adolescents. It presents
      with recurrent episodes of bone pain and fever, resembling bacterial
      osteomyelitis, but cultures of lesions are sterile and it is unresponsive to
      antibiotic therapy. We report a case of a 3-year-old boy diagnosed with CRMO, who
      was initially treated for bacterial osteomyelitis, and received prolonged
      antibiotic therapy for chronic pain, and swelling of mandible and ulna. CRMO
      should be kept in mind in the differential diagnosis of chronic bone pain and
      osteomyelitis unresponsive to antibiotic treatment. 

PMID- 26307647
TI  - Sequential argon-YAG laser membranotomy of extensive persistent pupillary
      membrane with visual loss.
AB  - A 20-year-old woman, a registered nurse, presented with best-corrected visual
      acuity of 6/15 (20/50) due to bilateral extensive persistent pupillary membrane.
      Sequential argon laser photocoagulation of the iris strands at the pupillary
      membrane iris collarette followed by neodymium:YAG laser lysis resulted in
      partial clearing of the central visual axis without bleeding. Best-corrected
      visual acuity improved to 6/9 (20/30) bilaterally without complications noted 1
      year after combined laser therapy. 

PMID- 26307648
TI  - An atypical case of vasospastic angina: demonstrating the usefulness of Holter
      monitoring.
AB  - Prinzmetal variant angina or vasospastic angina is a clinical syndrome
      characterised by episodic chest pain and transient reversible ST segment changes
      in ECG. The aetiology and treatment of the condition are quite different compared
      to those of conventional coronary artery disease. The crux of the problem in
      variant angina patients remains the diagnosis, especially if coexisting coronary
      artery disease is present. Timely diagnosis not only helps relieve symptoms, it
      also prevents complications such as ventricular tachycardia. Conventional
      provocative tests are used for diagnosis of such conditions; they have varied
      sensitively and specificity, and are cumbersome to perform. We present a case of
      an elderly man who presented with recurrent episodes of breathlessness and chest
      pain, where Holter monitoring proved to be a better mode for diagnosing variant
      angina than more invasive provocative tests. In this report, we reemphasis the
      role of this simple non-invasive diagnostic mode for diagnosis of variant angina.

PMID- 26307649
TI  - Lessons learnt from a case of multiple myeloma.

PMID- 26307650
TI  - Seizure induced polytrauma; not just posterior dislocation of the shoulder.
AB  - A 61-year-old woman sustained multiple fractures secondary to the tonic clonic
      muscular contractions of a seizure. Her injuries included: bilateral proximal
      humerus posterior fracture dislocations, manubrium fracture, unstable sixth
      thoracic vertebrae crush fracture, bilateral acetabular fractures and a left
      femoral neck fracture. Seizures are a rare but recognised cause of fracture.
      Patients with osteoporosis are more susceptible to more serious fractures to long
      bones, spine and pelvis. The lack of history of high-energy trauma can lead to a
      delay in diagnosis. Rarely, the combination and magnitude of these injuries can
      be life-threatening. 

PMID- 26307651
TI  - Gossypiboma: a hidden passenger.

PMID- 26307652
TI  - Diagnosis of an obturator hernia by CT.

PMID- 26307653
TI  - Unusual cause of intussusception.

PMID- 26307655
TI  - Surfactant-Directed Synthesis of Mesoporous Pd Films with Perpendicular
      Mesochannels as Efficient Electrocatalysts.
AB  - Palladium (Pd) films with perpendicularly aligned mesochannels are expected to
      provide fascinating electrocatalytic properties due to their low diffusion
      resistance and the full utilization of their large surface area. There have been
      no studies on such mesoporous metal films, because of the difficulties in
      controlling both the vertical alignment of the molecular template and the crystal
      growth in the metallic pore walls. Here we report an effective approach for the
      synthesis of mesoporous Pd films with mesochannels perpendicularly aligned to the
      substrate by an elaborated electrochemical deposition. The films show a superior
      electrocatalytic activity by taking full advantage of the perpendicularly aligned
      mesochannels. 

PMID- 26307656
TI  - Psychological distress among Vietnamese adults attending Vietnamese-speaking
      general practices in South Western Sydney: prevalence and associations.
AB  - Objective: The aim of the present study was to determine the prevalence of
      psychological distress among Vietnamese adults attending Vietnamese-speaking
      general practices and explore possible risk factors in this population.Methods: A
      cross-sectional survey of Vietnamese adult patients was conducted at 25 general
      practices with Vietnamese-speaking general practitioners (GPs) in south-western
      Sydney between October 2012 and February 2013. Patients completed the Kessler
      (K10) scale and a demographic questionnaire, available in Vietnamese or English.
      Data were analysed using SPSS version 21.Results: Of the 350 patients invited to
      participate, 247 completed surveys (response rate 71%). One-quarter (25%) of
      participants had a very high K10 score for psychological distress, nearly twice
      that reported in the NSW Health Survey. Participants with high exposure to trauma
      were at increased risk of psychological distress (odds ratio 5.9, 95% confidence
      interval 2.4-14.4; P < 0.0001) compared with those with mild or no trauma
      exposure. Similarly, risk was increased if there was a past history of mental
      health problems and a lack of personal and social support.Conclusion: The high
      prevalence of mental health problems in adult Vietnamese people attending
      Vietnamese-speaking general practices is associated with exposure to trauma. This
      highlights the importance of personal, social and professional support in
      effective management. Vietnamese-speaking GPs who see Vietnamese or similar
      refugee groups should actively seek out a history of exposure to trauma, a past
      history of mental illness and the existence of support systems.

PMID- 26307657
TI  - Staged hybrid approach for an acute-on-chronic aortic dissection with rupture in
      a Jehovah's Witness patient: Case report.

PMID- 26307654
TI  - Genome-wide association study of prostate cancer-specific survival.
AB  - BACKGROUND: Unnecessary intervention and overtreatment of indolent disease are
      common challenges in clinical management of prostate cancer. Improved tools to
      distinguish lethal from indolent disease are critical. METHODS: We performed a
      genome-wide survival analysis of cause-specific death in 24,023 prostate cancer
      patients (3,513 disease-specific deaths) from the PRACTICAL and BPC3 consortia.
      Top findings were assessed for replication in a Norwegian cohort (CONOR).
      RESULTS: We observed no significant association between genetic variants and
      prostate cancer survival. CONCLUSIONS: Common genetic variants with large impact
      on prostate cancer survival were not observed in this study. IMPACT: Future
      studies should be designed for identification of rare variants with large effect
      sizes or common variants with small effect sizes.

PMID- 26307658
TI  - Thiazovivin, a Rho kinase inhibitor, improves stemness maintenance of embryo
      derived stem-like cells under chemically defined culture conditions in cattle.
AB  - Despite numerous reported attempts, successful isolation of genuine embryonic
      stem cells of cattle has been rare. Previous studies have shown that Thiazovivin,
      a Rho-associated kinase inhibitor, improves the survival and self-renewal of
      human embryonic stem cells. The present study demonstrates the effect of
      Thiazovivin on the derivation of embryo-derived stem-like cells. Attachment rates
      of blastocyst and embryonic cell clumps onto feeder cells in the Thiazovivin
      treatment group were greater than those of the control group. The pluripotency
      markers of the OCT4 and NANOG genes, and the adhesion molecule E-cadherin were
      increased by Thiazovivin treatment. This study suggests that Thiazovivin
      treatment improves the maintenance of stemness in a putative stem-like cell
      populations of cattle by promoting the expression of pluripotency marker genes,
      as well as enhancing the expression of the E-cadherin gene, resulting in an
      increase in cell adhesion. 

PMID- 26307659
TI  - Pre-operative effects of the administration of systemic corticosteroids combined
      with antibiotics on a lobular capillary hemangioma in the nasal cavity.
AB  - Lobular capillary hemangiomas (LCHs), also known as pyogenic granulomas, are
      benign, rapidly growing hemorrhagic lesions that usually develop in the oral or
      nasal cavities. In adults, LCHs occur in <5% of all pregnant women. A 30-year-old
      woman presented with a 4-month history of right-sided nasal obstruction and
      recurrent epistaxis 2 months post-partum. A fragile, pink-red lobulated tumor
      existed in the anterior portion of the right inferior turbinate; the biopsy
      revealed a LCH. Although the patient declined surgery using an external approach,
      treatment with systemic corticosteroids combined with antibiotics resulted in
      tumor regression and an endoscopic en bloc resection was possible. No recurrence
      has been noted to date (>1 year after surgery). Pre-operative treatment with
      systemic corticosteroids combined with antibiotics may be useful to induce tumor
      regression and to excise the lesion completely with an endoscopic approach. 

PMID- 26307660
TI  - Cord blood irisin at the extremes of fetal growth.
AB  - BACKGROUND/AIMS: Irisin, a novel myokine with antiobesity properties, drives
      brown-fat-like conversion of white adipose tissue, thus increasing energy
      expenditure and improving glucose tolerance. We aimed to investigate circulating
      irisin concentrations in large-for-gestational-age (LGA) and intrauterine-growth
      restricted (IUGR) fetuses, both associated with metabolic dysregulation and long
      term susceptibility to obesity and metabolic syndrome development. METHODS:
      Plasma irisin and insulin concentrations were determined by ELISA and IRMA,
      respectively, in 80 mixed arteriovenous cord blood samples from LGA (n=30), IUGR
      (n=30) and appropriate-for-gestational-age (AGA, n=20) singleton full-term
      pregnancies. Fetuses were classified as LGA, IUGR or AGA, based on customized
      birth-weight standards adjusted for significant determinants of fetal growth.
      RESULTS: Fetal irisin concentrations were lower in IUGR cases than AGA controls
      (p=0.031). Cord blood irisin concentrations were similar in LGA and AGA groups
      and positively correlated with birth-weight, as well as customized centiles
      (r=0.245, p=0.029 and r=0.247, p=0.027, respectively). Insulin concentrations
      were higher in LGA, compared to AGA fetuses (p=0.036). In the LGA group, fetal
      irisin concentrations positively correlated with fetal insulin concentrations
      (r=0.374, p=0.042). CONCLUSIONS: Impaired skeletal muscle metabolism in IUGR
      fetuses may account for their irisin deficiency, which may be part of the fetal
      programming process, leading to increased susceptibility to later metabolic
      syndrome development. Furthermore, irisin down-regulation may predispose IUGR
      infants to hypothermia at birth, by inducing less "browning" of their adipose
      tissue and consequently less non-shivering thermogenesis. Irisin upregulation
      with increasing birth-weight may contribute to a slower fat gain during early
      infancy ("catch-down"), by promoting higher total energy expenditure. The
      positive correlation between irisin and insulin in the LGA group may reflect a
      counterbalance of the documented hyperinsulinemia, which is partly responsible
      for the excessive fat deposition in the LGA fetus.

PMID- 26307661
TI  - Chronic treadmill running does not enhance mitochondrial oxidative capacity in
      the cortex or striatum.
AB  - OBJECTIVE: The aims of the present study were to determine in healthy animals if
      1) acute exercise stimulated traditional exercise signaling pathways in the
      cortex and striatum, and 2) if chronic exercise training increased the oxidative
      capacity of these brain regions. METHODS: Male C57BL/6 mice were left sedentary,
      acutely exercised for 15 or 60 min to examine potential signaling cascades
      activated by exercise, or chronically exercise for 4 wk to examine the impact of
      prolonged training. The cortex and striatum were analyzed for changes in the
      phosphorylation of AMPK, CAMKII, ERK1/2, and P38 with acute exercise, or markers
      of mitochondrial protein content, mtDNA copy number, and mitochondrial
      respiration with chronic exercise. RESULTS: In mice, acute treadmill running did
      not alter the phosphorylation of AMPK, CAMKII, or P38 in either the cortex or the
      striatum, but decreased ERK1/2 phosphorylation in only the cortex for the
      duration of the exercise bout. Following chronic exercise training, mitochondrial
      respiration, mtDNA copy number, and protein content of various subunits of the
      electron transport chain were not altered in adult mice. CONCLUSION: Combined,
      these data suggest that exercise does not result in increased phosphorylation of
      traditional signaling kinases or enhanced mitochondrial oxidative capacity in
      either the cortex or the striatum of healthy animals.

PMID- 26307664
TI  - Aromadendrane and cyclofarnesane sesquiterpenoids from cultures of the
      basidiomycete Inonotus sp. BCC 23706.
AB  - Twelve aromadendrane sesquiterpenoids, inonotins A-L, and a previously unknown
      cyclofarnesane, i.e., inonofarnesane, together with two known compounds, were
      isolated from cultures of the wood-rotting basidiomycete Inonotus sp. BCC 23706.
      Inonotin I is identical to a previously reported compound with an incorrect
      structure. Structures of the compounds were elucidated by spectroscopic analysis
      and X-ray crystallography. The absolute configurations of inonotin D and
      inonofarnesane were determined by application of the modified Mosher's method. 

PMID- 26307666
TI  - Imaging findings in cardiac masses (Part I): study protocol and benign tumors.
AB  - Cardiac masses represent a diagnostic challenge because decisions about treatment
      are based on imaging techniques. Echocardiography, magnetic resonance (MR) and
      computed tomography (CT) are fundamental for the detection, characterization, and
      staging of cardiac masses as well as for planning their treatment. Most primary
      cardiac tumors are benign; myxomas, papillary fibroelastomas, and lipomas are the
      most common. The location of the tumors and its characteristics on CT and MR
      orient the etiologic diagnosis in most cases. This article describes the
      protocols for CT and MR studies of cardiac masses as well as the morphologic
      findings, predominant locations, and most useful characteristics for
      characterizing benign cardiac masses and establishing the differential diagnosis
      with malignant cardiac tumors and non-neoplastic pseudotumors. 

PMID- 26307665
TI  - Foxp3(+) T cells expressing RORgammat represent a stable regulatory T-cell
      effector lineage with enhanced suppressive capacity during intestinal
      inflammation.
AB  - Foxp3 (forkhead box P3 transcription factor)-expressing regulatory T cells
      (Tregs) are essential for immunological tolerance, best illustrated by
      uncontrolled effector T-cell responses and autoimmunity upon loss of Foxp3
      expression. Tregs can adopt specific effector phenotypes upon activation,
      reflecting the diversity of functional demands in the different tissues of the
      body. Here, we report that Foxp3(+)CD4(+) T cells coexpressing retinoic acid
      related orphan receptor-gammat (RORgammat), the master transcription factor for T
      helper type 17 (Th17) cells, represent a stable effector Treg lineage.
      Transcriptomic and epigenetic profiling revealed that Foxp3(+)RORgammat(+) T
      cells display signatures of both Tregs and Th17 cells, although the degree of
      similarity was higher to Foxp3(+)RORgammat(-) Tregs than to Foxp3(-)RORgammat(+)
      T cells. Importantly, Foxp3(+)RORgammat(+) T cells were significantly
      demethylated at Treg-specific epigenetic signature genes such as Foxp3, Ctla-4,
      Gitr, Eos, and Helios, suggesting that these cells have a stable regulatory
      rather than inflammatory function. Indeed, adoptive transfer of
      Foxp3(+)RORgammat(+) T cells in the T-cell transfer colitis model confirmed their
      Treg function and lineage stability in vivo, and revealed an enhanced suppressive
      capacity as compared with Foxp3(+)RORgammat(-) Tregs. Thus, our data suggest that
      RORgammat expression in Tregs contributes to an optimal suppressive capacity
      during gut-specific immune responses, rendering Foxp3(+)RORgammat(+) T cells as
      an important effector Treg subset in the intestinal system. 

PMID- 26307667
TI  - Gene Therapy Restores Hair Cell Stereocilia Morphology in Inner Ears of Deaf
      Whirler Mice.
AB  - Hereditary deafness is one of the most common disabilities affecting newborns.
      Many forms of hereditary deafness are caused by morphological defects of the
      stereocilia bundles on the apical surfaces of inner ear hair cells, which are
      responsible for sound detection. We explored the effectiveness of gene therapy in
      restoring the hair cell stereocilia architecture in the whirlin mouse model of
      human deafness, which is deaf due to dysmorphic, short stereocilia. Wild-type
      whirlin cDNA was delivered via adeno-associated virus (AAV8) by injection through
      the round window of the cochleas in neonatal whirler mice. Subsequently, whirlin
      expression was detected in infected hair cells (IHCs), and normal stereocilia
      length and bundle architecture were restored. Whirlin gene therapy also increased
      inner hair cell survival in the treated ears compared to the contralateral
      nontreated ears. These results indicate that a form of inherited deafness due to
      structural defects in cochlear hair cells is amenable to restoration through gene
      therapy. 

PMID- 26307670
TI  - Erratum: Exposure to a youthful circulation rejuvenates bone repair through
      modulation of beta-catenin.

PMID- 26307668
TI  - Suppression of EZH2 Prevents the Shift of Osteoporotic MSC Fate to Adipocyte and
      Enhances Bone Formation During Osteoporosis.
AB  - During osteoporosis, the shift of mesenchymal stem cell (MSC) lineage commitment
      to adipocyte leads to the imbalance between bone mass and fat, which increases
      the risk of fracture. The Enhancer of Zeste homology 2 (EZH2), which methylates
      histone H3 on lysine 27 (H3K27me3), controls MSC cell lineage commitment.
      However, whether EZH2 is related to osteoporosis remains elusive. In our study,
      we found EZH2 expression was significantly increased in osteoporotic MSCs. EZH2
      directly increased H3K27me3 levels on promoters of Wnt1, Wnt6, and Wnt10a to
      silence Wnt gene transcription. The inhibition of Wnt/beta-catenin signaling
      shifted MSC cell lineage commitment to adipocyte. Knockdown of EZH2 by lentivirus
      expressing shRNA rescued the abnormal fate of osteoporotic MSC. By employing the
      H3K27me3 inhibitor DZNep, we effectively derepressed Wnt signaling and improved
      osteogenic differentiation of osteoporotic MSCs in vitro. Furthermore, in vivo
      administration of DZNep successfully increased bone formation and repressed
      excessive bone marrow fat formation in osteoporotic mice. Noteworthy, DZNep
      treatment persistently enhanced osteogenic differentiation of endogenous MSCs. In
      conclusion, our study demonstrated that redundant EZH2 shifted MSC cell lineage
      commitment to adipocyte, which contributed to the development of osteoporosis. We
      also provided EZH2 as a novel therapeutic target for improving bone formation
      during osteoporosis. 

PMID- 26307669
TI  - Syndecan 4 Mediates Nrf2-dependent Expansion of Bronchiolar Progenitors That
      Protect Against Lung Inflammation.
AB  - The use of lung progenitors for regenerative medicine appears promising, but
      their biology is not fully understood. Here, we found anti-inflammatory
      attributes in bronchiolar progenitors that were sorted as a multipotent subset of
      mouse club cells and found to express secretory leukocyte protease inhibitor
      (SLPI). Notably, the impaired expression of SLPI in mice increased the number of
      bronchiolar progenitors and decreased the lung inflammation. We determined a
      transcriptional profile for the bronchiolar progenitors of Slpi-deficient mice
      and identified syndecan 4, whose expression was markedly elevated as compared to
      that of wild-type mice. Systemic administration of recombinant syndecan 4 protein
      caused a substantial increase in the number of bronchiolar progenitors with
      concomitant attenuation of both airway and alveolar inflammation. The syndecan 4
      administration also resulted in activation of the Keap1-Nrf2 antioxidant pathway
      in lung cells, which is critically involved in the therapeutic responses to the
      syndecan 4 treatment. Moreover, in 3D culture, the presence of syndecan 4 induced
      differentiated club cells to undergo Nrf2-dependent transition into bronchiolar
      progenitors. Our observations reveal that differentiative switches between
      bronchiolar progenitors and club cells are under the Nrf2-mediated control of
      SLPI and syndecan 4, suggesting the possibility of new therapeutic approaches in
      inflammatory lung diseases. 

PMID- 26307671
TI  - Coupling of lysosomal and mitochondrial membrane permeabilization in trypanolysis
      by APOL1.
AB  - Humans resist infection by the African parasite Trypanosoma brucei owing to the
      trypanolytic activity of the serum apolipoprotein L1 (APOL1). Following uptake by
      endocytosis in the parasite, APOL1 forms pores in endolysosomal membranes and
      triggers lysosome swelling. Here we show that APOL1 induces both lysosomal and
      mitochondrial membrane permeabilization (LMP and MMP). Trypanolysis coincides
      with MMP and consecutive release of the mitochondrial TbEndoG endonuclease to the
      nucleus. APOL1 is associated with the kinesin TbKIFC1, of which both the motor
      and vesicular trafficking VHS domains are required for MMP, but not for LMP. The
      presence of APOL1 in the mitochondrion is accompanied by mitochondrial membrane
      fenestration, which can be mimicked by knockdown of a mitochondrial mitofusin
      like protein (TbMFNL). The BH3-like peptide of APOL1 is required for LMP, MMP and
      trypanolysis. Thus, trypanolysis by APOL1 is linked to apoptosis-like MMP
      occurring together with TbKIFC1-mediated transport of APOL1 from endolysosomal
      membranes to the mitochondrion. 

PMID- 26307672
TI  - Diagnostic value of antibody responses to multiple antigens from Mycobacterium
      tuberculosis in active and latent tuberculosis.
AB  - We investigated the antibody responses to 10 prospective Mycobacterium
      tuberculosis (MTB) antigens and evaluated their ability to discriminate between
      latent (LTBI) and active pulmonary tuberculosis (TB). Our results indicate that
      plasma levels of anti-alpha-crystallin (ACR), antilipoarabinomannan, anti
      trehalose 6,6'-dimycolate, and anti-tubercular-glycolipid antigen antibodies were
      higher in patients with active TB, compared to those in the LTBI and control
      subjects. No differences in the antibodies were observed between the control and
      LTBI subjects. Antibodies against the glycolipid antigens could not distinguish
      between Mycobacterium avium complex (MAC)-negative TB patients and MAC-infected
      LTBI individuals. The most useful serological marker was antibodies to ACR, with
      MAC-negative TB patients having higher titers than those observed in MAC-positive
      LTBI and control subjects. Our data indicate that antibody to ACR is a promising
      target for the serological diagnosis of patients with active TB patients. When
      dealing with antiglycolipid antibodies, MAC coinfection should always be
      considered in serological studies. 

PMID- 26307674
TI  - Verhulst and stochastic models for comparing mechanisms of MAb productivity in
      six CHO cell lines.
AB  - The present study validates previously published methodologies-stochastic and
      Verhulst-for modelling the growth and MAb productivity of six CHO cell lines
      grown in batch cultures. Cytometric and biochemical data were used to model
      growth and productivity. The stochastic explanatory models were developed to
      improve our understanding of the underlying mechanisms of growth and
      productivity, whereas the Verhulst mechanistic models were developed for their
      predictability. The parameters of the two sets of models were compared for their
      biological significance. The stochastic models, based on the cytometric data,
      indicated that the productivity mechanism is cell specific. However, as shown
      before, the modelling results indicated that G2 + ER indicate high productivity,
      while G1 + ER indicate low productivity, where G1 and G2 are the cell cycle
      phases and ER is Endoplasmic Reticulum. In all cell lines, growth proved to be
      inversely proportional to the cumulative G1 time (CG1T) for the G1 phase, whereas
      productivity was directly proportional to ER. Verhulst's rule, "the lower the
      intrinsic growth factor (r), the higher the growth (K)," did not hold for growth
      across all cell lines but held good for the cell lines with the same growth
      mechanism-i.e., r is cell specific. However, the Verhulst productivity rule, that
      productivity is inversely proportional to the intrinsic productivity factor (r x
      ), held well across all cell lines in spite of differences in their mechanisms
      for productivity-that is, r x is not cell specific. The productivity profile, as
      described by Verhulst's logistic model, is very similar to the Michaelis-Menten
      enzyme kinetic equation, suggesting that productivity is more likely enzymatic in
      nature. Comparison of the stochastic and Verhulst models indicated that CG1T in
      the cytometric data has the same significance as r, the intrinsic growth factor
      in the Verhulst models. The stochastic explanatory and the Verhulst logistic
      models can explain the differences in the productivity of the six clones. 

PMID- 26307675
TI  - Application of HC-AFW1 Hepatocarcinoma Cells for Mechanistic Studies: Regulation
      of Cytochrome P450 2B6 Expression by Dimethyl Sulfoxide and Early Growth Response
      1.
AB  - Various exogenous compounds, for example, the drugs bupropione and propofol, but
      also various cytostatics, are metabolized in the liver by the enzyme cytochrome
      P450 (P450) CYP2B6. Transcription from the CYP2B6 gene is regulated mainly via
      the transcription factors constitutive androstane receptor (CAR) and pregnane-X
      receptor (PXR). Most hepatic cell lines express no or only low levels of CYP2B6
      because of loss of these two regulators. Dimethyl sulfoxide (DMSO) is frequently
      used in liver cell cultivation and is thought to affect the expression of various
      P450 isoforms by inducing or preserving cellular differentiation. We studied the
      effects of up to 1.5% of DMSO as cell culture medium supplement on P450
      expression in hepatocarcinoma cells from line HC-AFW1. DMSO did not induce
      differentiation of the HC-AFW1 cell line, as demonstrated by unaltered levels of
      selected mRNA markers important for hepatocyte differentiation, and also by the
      lack of a DMSO effect on a broader spectrum of P450s. By contrast, CYP2B6 mRNA
      was strongly induced by DMSO. This process was independent of CAR or PXR
      activation. Interestingly, elevated transcription of CYP2B6 was accompanied by a
      simultaneous induction of early growth response 1 (EGR1), a transcription factor
      known to influence the expression of CYP2B6. Expression of wild-type EGR1 or of a
      truncated, dominant-negative EGR1 mutant was able to mimic or attenuate the DMSO
      effect, respectively. These findings demonstrate that EGR1 is involved in the
      regulation of CYP2B6 by DMSO in HC-AFW1 cells. 

PMID- 26307673
TI  - A caveolin-dependent and PI3K/AKT-independent role of PTEN in beta-catenin
      transcriptional activity.
AB  - Loss of the tumour suppressor PTEN is frequent in human melanoma, results in MAPK
      activation, suppresses senescence and mediates metastatic behaviour. How PTEN
      loss mediates these effects is unknown. Here we show that loss of PTEN in
      epithelial and melanocytic cell lines induces the nuclear localization and
      transcriptional activation of beta-catenin independent of the PI3K-AKT-GSK3beta
      axis. The absence of PTEN leads to caveolin-1 (CAV1)-dependent beta-catenin
      transcriptional modulation in vitro, cooperates with NRAS(Q61K) to initiate
      melanomagenesis in vivo and induces efficient metastasis formation associated
      with E-cadherin internalization. The CAV1-beta-catenin axis is mediated by a
      feedback loop in which beta-catenin represses transcription of miR-199a-5p and
      miR-203, which suppress the levels of CAV1 mRNA in melanoma cells. These data
      reveal a mechanism by which loss of PTEN increases CAV1-mediated dissociation of
      beta-catenin from membranous E-cadherin, which may promote senescence bypass and
      metastasis. 

PMID- 26307676
TI  - Anxa2 binds to STAT3 and promotes epithelial to mesenchymal transition in breast
      cancer cells.
AB  - Overexpression of annexin A2 (Anxa2) is correlated with invasion and metastasis
      in breast cancer cells. In this study, breast cancer patients with upregulated
      Anxa2 exhibited poor overall and disease-free survival rates. Anxa2 expression
      was also positively correlated with the expression of epidermal growth factor
      receptor (EGFR) and epithelial-mesenchymal transition (EMT) markers in breast
      cancer tissues and cell lines. Moreover, knockdown of Anxa2 impaired EGF-induced
      EMT, as well as the migration and invasion of breast cancer cells in vitro.
      Meanwhile, Anxa2 depletion significantly ablated pulmonary metastasis in a severe
      combined immunodeficiency mouse model of breast cancer. Importantly, Anxa2
      reduction inhibited EGF-induced activation of STAT3, which is required for EGF
      induced EMT. Anxa2 directly bound to STAT3 and enhanced its transcriptional
      activity, thereby indicating that Anxa2 promotes EGF-induced EMT in a STAT3
      dependent manner. Our findings provide clinical evidence that Anxa2 is a poor
      prognostic factor for breast cancer and reveal a novel mechanism through which
      Anxa2 promotes breast cancer metastasis. 

PMID- 26307677
TI  - Perifosine as a potential novel anti-telomerase therapy.
AB  - Most tumors circumvent telomere-length imposed replicative limits through
      expression of telomerase, the reverse transcriptase that maintains telomere
      length. Substantial evidence that AKT activity is required for telomerase
      activity exists, indicating that AKT inhibitors may also function as telomerase
      inhibitors. This possibility has not been investigated in a clinical context
      despite many clinical trials evaluating AKT inhibitors. We tested if Perifosine,
      an AKT inhibitor in clinical trials, inhibits telomerase activity and telomere
      maintenance in tissue culture and orthotopic xenograft models as well as in
      purified CLL samples from a phase II Perifosine clinical trial. We demonstrate
      that Perifosine inhibits telomerase activity and induces telomere shortening in a
      wide variety of cell lines in vitro, though there is substantial heterogeneity in
      long-term responses to Perifosine between cell lines. Perifosine did reduce
      primary breast cancer orthotopic xenograft tumor size, but did not impact
      metastatic burden in a statistically significant manner. However, Perifosine
      reduced telomerase activity in four of six CLL patients evaluated. Two of the
      patients were treated for four to six months and shortening of the shortest
      telomeres occurred in both patients' cells. These results indicate that it may be
      possible to repurpose Perifosine or other AKT pathway inhibitors as a novel
      approach to targeting telomerase. 

PMID- 26307678
TI  - Achaete scute-like 2 suppresses CDX2 expression and inhibits intestinal
      neoplastic epithelial cell differentiation.
AB  - The role of Achaete scute-like 2 (Ascl2) in colorectal cancer (CRC) cell
      differentiation is unknown. LS174T, HT-29 and Caco-2 cells have high Ascl2
      expression, while Lovo and SW480 cells have low Ascl2 expression. LS174T and HT
      29 cells with Ascl2 knockdown were transfected with caudal type homeobox 2 (CDX2)
      promoter constructs and used for luciferase assays and chromatin
      immunoprecipitation (ChIP) assays. Ascl2 knockdown promoted differentiation of
      CRC cells into a goblet cell phenotype, as determined by increased expression of
      MUC2, TFF3, and CDX2. Ascl2 knockdown activated CDX2 expression through a
      transcriptional mechanism via direct binding of Ascl2 to the proximal E-box of
      the CDX2 promoter. Ascl2 over-expression in Lovo and SW480 cells inhibited a
      goblet cell phenotype, as determined by reduced CDX2 and MUC2 expression. Inverse
      correlations between Ascl2 and CDX2, and Ascl2 and MUC2 mRNA levels, as well as
      Ascl2 and CDX2 protein levels were observed in CRC cancerous samples. This study
      demonstrates CDX2 repression by Ascl2 and highlights a role for Ascl2 in CRC cell
      differentiation. These findings suggest that the Ascl2/CDX2 axis may serve as a
      potential therapeutic target in colorectal cancer. 

PMID- 26307679
TI  - Transcriptome analysis indicates TFEB1 and YEATS4 as regulatory transcription
      factors for drug resistance of ovarian cancer.
AB  - Ovarian cancer is an intractable disease because patients with ovarian cancer
      frequently develop drug resistance after long-term chemotherapy. Despite the
      availability of cumulative information on drug-resistant patients, strategies to
      reverse drug resistance have still not been established. In this study, we
      analyzed drug resistance-associated transcription factors (TFs) in ovarian
      cancer. Gene expression profiles of 15 drug-resistant and 11 drug-sensitive
      patients with ovarian cancer were compared. Our results showed that TFs TFEB1 and
      YEATS4 regulated the expression of downstream target genes. These 2 TFs have
      already been implicated in tumorigenesis or metastasis. To our knowledge, this is
      the first study to evaluate the involvement of these TFs in drug resistance of
      ovarian cancer. Interestingly, 70% knockdown of each of these TFs with siRNAs
      resulted in approximately 20%~30% recovery of drug sensitivity. Further,
      combination treatment of ovarian cancer cells with TFEB1 and YEATS4 siRNAs
      resulted in 35% reversal of drug resistance. The effect of these TFs on
      chemoresistance seemed to be associated with intrinsic apoptosis-related
      pathways, such as p53 activation, and not with the suppression of drug transport.
      Thus, we suggest a novel approach to reverse chemoresistance of ovarian cancer by
      suppressing TFEB1 and YEATS4. 

PMID- 26307680
TI  - CEBPD amplification and overexpression in urothelial carcinoma: a driver of tumor
      metastasis indicating adverse prognosis.
AB  - The molecular aberrations responsible for the progression of urothelial carcinoma
      (UC) remain largely obscure. To search candidate driver oncogenes in UC, we
      performed array-based genomic hybridization (aCGH) on 40 UBUC samples.
      Amplification of 8q11.21 was preferentially identified in patients who developed
      disease-specific death (53.8%) and distal metastasis (50.0%) but was barely
      detected in non-eventful cases (3.7% and 0%, respectively). In order to quantify
      the expression of candidate genes harbored in 8q11.21, laser-capture
      microdissection coupled with RT-PCR was performed on 32 of the 40 cases submitted
      to aCGH. With this, we identified CEBPD mRNA expression as most significantly
      associated with gains of 8q11.21, suggesting amplification-driven expression. By
      performing CEBPD-specific FISH and immunohistochemistry on 295 UBUCs, we
      confirmed CEBPD amplification (21.3%) and overexpression (29.8%) were strongly
      related to each other (p<0.001). Moreover, both were associated with adverse
      clinicopathologic features and worse outcomes. Furthermore, the clinical
      significance of CEBPD expression was also confirmed in an independent cohort
      comprised of 340 UCs from the upper urinary tract. Interestingly, CEBPD knockdown
      suppressed cell proliferation, migration and, most significantly, cell invasion
      ability in UC cells. The latter phenotype is attributed to downregulation of MMP2
      as identified by RT2 Profiler PCR array. Moreover, expression of CEBPD
      significantly enhanced MMP2 expression and transcriptional activation by directly
      binding to its promoter region, as confirmed by promoter reporter assay and
      chromatin immunoprecipitation assay. Conclusively, CEBPD amplification is a
      mechanism driving increased mRNA and protein expression that confers
      aggressiveness in UC through MMP2-mediated cell invasiveness. 

PMID- 26307681
TI  - Aberrant mesenchymal differentiation of glioma stem-like cells: implications for
      therapeutic targeting.
AB  - Differentiation has been proposed as a therapeutic strategy for glioblastoma
      (GBM) in part due to observations of stem-like cells in GBM that have been shown
      to undergo terminal differentiation in response to growth factor withdrawal and
      BMP activation. However, the effects of long term exposure to serum culture
      conditions on glioma sphere cultures/glioma stem-like cells (GSCs) have not been
      examined. Here we show that GSCs retained both neurosphere formation and tumor
      initiation abilities after short or long term serum exposure. Under these
      conditions, GSCs expressed both neural lineage and stem cell markers,
      highlighting the aberrant pseudo-differentiation state. GSCs maintained under
      adherent serum cultured conditions continued to proliferate and initiate tumor
      formation with efficiencies similar to GSCs maintained under proliferating
      (neurosphere) conditions. Proneural (PN) GSCs under serum exposure showed an
      induction of mesenchymal (MES) gene expression signatures. Our data indicate that
      exposure to serum containing media result in aberrant differentiation (e.g.
      toward MES lineage) and activation of alternative oncogenic pathways in GSCs. 

PMID- 26307682
TI  - Cell context-dependent dual effects of EFEMP1 stabilizes subpopulation
      equilibrium in responding to changes of in vivo growth environment.
AB  - Conflicting functions of EFEMP1 in cancer have been reported. Using two syngeneic
      glioma cell lines (U251 and U251-NS) carrying two different principal cell
      subpopulations that express high or low EGFR, and that are able to interconvert
      via mis-segregation of chromosome 7 (Chr7), we studied EFEMP1's cell-context
      dependent functions in regulating subpopulation equilibrium, here defined by the
      percentage of cells carrying different copies of Chr7. We found that EFEMP1
      attenuated levels of EGFR and cellular respiration in high-EGFR-expressing cells,
      but increased levels of NOTCH1, MMP2, cell invasiveness, and both oxidative
      phosphorylation and glycolytic respiration in low-EGFR-expressing cells.
      Consistently, EFEMP1 suppressed intracranial xenograft formation in U251 and
      promoted its formation in U251-NS. Interestingly, subpopulation equilibria in
      xenografts of U251-NS without EFEMP1 overexpression were responsive to inoculum
      size (1, 10 and 100 thousand cells), which may change the tumor-onset
      environment. It was not observed in xenografts of U251-NS with EFEMP1
      overexpression. The anti-EGFR function of EFEMP1 suppressed acceleration of
      growth of U251-NS, but not the subpopulation equilibrium, when serially passed
      under a different (serum-containing adherent) culture condition. Overall, the
      data suggest that the orthotopic environment of the brain tumor supports EFEMP1
      in carrying out both its anti-EGFR and pro-invasive/cancer stem cell-transforming
      functions in the two glioma cell subpopulations during formation of a single
      tumor, where EFEMP1 stabilizes the subpopulation equilibrium in response to
      alterations of the growth environment. This finding implies that EFEMP1 may
      restrain cancer plasticity in coping with ever-changing tumor microenvironments
      and/or therapeutic-intervention stresses. 

PMID- 26307683
TI  - Role of dual specificity tyrosine-phosphorylation-regulated kinase 1B (Dyrk1B) in
      S-phase entry of HPV E7 expressing cells from quiescence.
AB  - The high-risk human papillomavirus (HPV) is the causative agent for cervical
      cancer. The HPV E7 oncogene promotes S-phase entry from quiescent state in the
      presence of elevated cell cycle inhibitor p27Kip1, a function that may contribute
      to carcinogenesis. However, the mechanism by which HPV E7 induces quiescent cells
      to entry into S-phase is not fully understood. Interestingly, we found that
      Dyrk1B, a dual-specificity kinase and negative regulator of cell proliferation in
      quiescent cells, was upregulated in E7 expressing cells. Surprisingly and in
      contrast to what was previously reported, Dyrk1B played a positive role in S
      phase entry of quiescent HPV E7 expressing cells. Mechanistically, Dyrk1B
      contributed to p27 phosphorylation (at serine 10 and threonine 198), which was
      important for the proliferation of HPV E7 expressing cells. Moreover, Dyrk1B up
      regulated HPV E7. Taken together, our studies uncovered a novel function of
      Dyrk1B in high-risk HPV E7-mediated cell proliferation. Dyrk1B may serve as a
      target for therapy in HPV-associated cancers. 

PMID- 26307685
TI  - Caesarean section and image consciousness among barriers to breast feeding for
      obese women.

PMID- 26307684
TI  - MicroRNA-224 is implicated in lung cancer pathogenesis through targeting caspase
      3 and caspase-7.
AB  - We recently reported that miR-224 was significantly up-regulated in non-small
      cell lung cancer (NSCLC) tissues, in particular in resected NSCLC metastasis. We
      further demonstrated that miR-224 functions as an oncogene in NSCLC by directly
      targeting TNFAIP1 and SMAD4. However, the biological functions of miR-224 in
      NSCLC are controversial and underlying mechanisms of miR-224 in the progression
      and metastasis of lung cancer remain to be further explored. Here we report that
      caspase3 (CASP3) and caspase7 (CASP7) are previously unidentified targets of miR
      224 in NSCLC, and that miR-224 promotes lung cancer cells proliferation and
      migration in part by directly targeting CASP7 and down-regulating its expression.
      In addition, miR-224 attenuated TNF-alpha induced apoptosis by direct targeting
      of CASP3 resulting in reduction of cleaved PARP1 expression in lung cancer cells.
      Furthermore, the expression of miR-224 negatively correlates with the expression
      of CASP7 and CASP3 in tissue samples from patients with lung cancer. Finally, we
      found that activated NF-kappaB signaling is involved in the regulation of miR-224
      expression in lung cancer. Our study provides new insight in understanding of
      oncogenic role of miR-224 in the lung cancer pathogenesis and suggests that NF
      kappaB/miR-224/CASP3, 7 pathway could be a putative therapeutic target in lung
      cancer. 

PMID- 26307686
TI  - Influence of different oocyte insemination techniques on early and late
      morphokinetic parameters: retrospective analysis of 500 time-lapse monitored
      blastocysts.
AB  - OBJECTIVE: To determine how standard IVF vs. intracytoplasmic sperm injection
      (ICSI) fertilization influences early and late morphokinetic parameters during
      prolonged embryo culture. DESIGN: Five-hundred expanded blastocysts that were
      monitored in a time-lapse monitoring incubator were analysed retrospectively.
      Early (pronuclear fading [PNf], t2-t9) and late (start of blastulation, expanded
      blastocyst) morphokinetic variables were scored according to published consensus
      criteria. SETTING: Private infertility clinic. PATIENT(S): A total of 209
      consecutive infertile patients (mean +/- SD age, 38.4 +/- 4 years; range, 28-47
      years) undergoing 238 natural IVF/minimal ovarian stimulation cycles during 2012
      2014. INTERVENTION(S): Minimal ovarian stimulation, oocyte retrieval,
      fertilization with standard IVF or ICSI, prolonged embryo culture in a time-lapse
      monitoring incubator. MAIN OUTCOME MEASURE(S): Differences in morphokinetic
      parameters according to insemination techniques. RESULT(S): In total, 29% and 71%
      of the whole cohort was fertilized with standard IVF and ICSI, respectively.
      During early cleavage stages (PNf to t4) there was a statistically significant
      delay (+1.5 to +1.1 hours) among IVF-fertilized embryos. By contrast, at the
      expanded blastocyst stage IVF-fertilized embryos showed faster development (-3.3
      to -4.1 hours). After normalizing to the time point of PNf, differences in
      cleavage-stage parameters disappeared, but those at all blastocyst stages
      increased even further in favor of IVF-fertilized embryos (-3.2 to -5.7 hours).
      CONCLUSION(S): The observed 1.5-hour time difference between standard IVF- and
      ICSI-fertilized embryos is an artificial phenomenon. At the blastocyst stages,
      however, genuine timing differences arise between IVF- and ICSI-fertilized
      embryos, possibly related to their different quality. Normalization to a common
      time point permits the joint analysis of IVF- and ICSI-fertilized embryos, thus
      increasing the size of studied cohorts.

PMID- 26307687
TI  - Clutch size of a vole-eating bird of prey as an indicator of vole abundance.
AB  - Voles are often considered as harmful pests in agriculture and silviculture.
      Then, the knowledge of their abundance may be of considerable economical
      importance. Commonly used methods in the monitoring of vole abundances are
      relatively laborious, expensive, and spatially quite restricted. We demonstrate
      how the mean clutch size of the tawny owl Strix aluco may be cost-effectively
      used to predict relative densities of voles over large areas. Besides installing
      a number of suitable nest boxes, this vole monitoring system primarily includes
      only the inspection of the nest boxes and counting the number of tawny owl eggs
      found two times during a few weeks period in spring. Our results showed a
      considerable agreement between the fluctuations in the mean clutch size of tawny
      owls and the late spring abundance indices of small voles (Myodes, Microtus) in
      our study areas in southern Finland. The mean clutch size of the tawny owl
      reflected spring vole abundance over the spatial range examined, suggesting its
      suitability for general forecasting purposes. From the pest management point of
      view, an additional merit of the present method is that it may increase numbers
      of vole-eaters that provide biological control of vole populations. 

PMID- 26307688
TI  - An integrated, multisensor system for the continuous monitoring of water dynamics
      in rice fields under different irrigation regimes.
AB  - The cultivation of rice, one of the most important staple crops worldwide, has
      very high water requirements. A variety of irrigation practices are applied,
      whose pros and cons, both in terms of water productivity and of their effects on
      the environment, are not completely understood yet. The continuous monitoring of
      irrigation and rainfall inputs, as well as of soil water dynamics, is a very
      important factor in the analysis of these practices. At the same time, however,
      it represents a challenging and costly task because of the complexity of the
      processes involved, of the difference in nature and magnitude of the driving
      variables and of the high variety of field conditions. In this paper, we present
      the prototype of an integrated, multisensor system for the continuous monitoring
      of water dynamics in rice fields under different irrigation regimes. The system
      consists of the following: (1) flow measurement devices for the monitoring of
      irrigation supply and tailwater drainage; (2) piezometers for groundwater level
      monitoring; (3) level gauges for monitoring the flooding depth; (4) multilevel
      tensiometers and moisture sensor clusters to monitor soil water status; (5) eddy
      covariance station for the estimation of evapotranspiration fluxes and (6)
      wireless transmission devices and software interface for data transfer, storage
      and control from remote computer. The system is modular and it is replicable in
      different field conditions. It was successfully applied over a 2-year period in
      three experimental plots in Northern Italy, each one with a different water
      management strategy. In the paper, we present information concerning the
      different instruments selected, their interconnections and their integration in a
      common remote control scheme. We also provide considerations and figures on the
      material and labour costs of the installation and management of the system. 

PMID- 26307689
TI  - Trace elements in different land use soils of Bangladesh and potential ecological
      risk.
AB  - Bogra city is highly susceptible to environmental pollution due to
      overpopulation, rapid industrialization, and urbanization during the last
      decades. The levels of six trace elements (chromium, nickel, copper, arsenic,
      cadmium, and lead) in seven different land use soils in Bangladesh were assessed.
      The ranges of Cr, Ni, Cu, As, Cd, and Pb in studied soils were 6.3-256, 8.3-271,
      13-279, 7.5-87, 0.09-29, and 5.3-624 mg/kg, respectively. The pollution load
      index (PLI) values for all land uses were higher than 1, indicating the
      progressive deterioration of soil due to trace elements contamination. In view of
      the potential ecological risk (PER), soils from all land uses showed moderate to
      very high potential ecological risk. Among the elements, As and Cd showed a
      higher potential ecological risk than the others. 

PMID- 26307690
TI  - Determination and mapping the spatial distribution of radioactivity of natural
      spring water in the Eastern Black Sea Region by using artificial neural network
      method.
AB  - In this study, radiological distribution of gross alpha, gross beta, (226)Ra,
      (232)Th, (40)K, and (137)Cs for a total of 40 natural spring water samples
      obtained from seven cities of the Eastern Black Sea Region was determined by
      artificial neural network (ANN) method. In the ANN method employed, the
      backpropagation algorithm, which estimates the backpropagation of the errors and
      results, was used. In the structure of ANN, five input parameters (latitude,
      longitude, altitude, major soil groups, and rainfall) were used for natural
      radionuclides and four input parameters (latitude, longitude, altitude, and
      rainfall) were used for artificial radionuclides, respectively. In addition, 75 %
      of the total data were used as the data of training and 25 % of them were used as
      test data in order to reveal the structure of each radionuclide. It has been seen
      that the results obtained explain the radiographic structure of the region very
      well. Spatial interpolation maps covering the whole region were created for each
      radionuclide including spots not measured by using these results. It has been
      determined that artificial neural network method can be used for mapping the
      spatial distribution of radioactivity with this study, which is conducted for the
      first time for the Black Sea Region.

PMID- 26307691
TI  - A newborn with severe skeletal dysplasia.

PMID- 26307692
TI  - Unveiling the intricacies of the curved-field ion mirror.
AB  - In time-of-flight (ToF) mass spectrometry, non-linear ion mirrors, i.e. mirrors
      that produce a non-linear potential in which the ions fly, can focus ions
      exhibiting a very broad kinetic energy distribution. Besides the quadratic
      potential, the so-called curved field has been used in mirrors as a non-linear
      potential over the past 20 years. The curved field has, however, only been
      loosely defined. The focusing properties of the curved field appear to have never
      been mathematically investigated and explained. In this work, we put forward a
      rigid definition of the curved field and investigate the properties of it in
      terms of focusing and transmission. This rigid definition shows the curved field
      as a two-parameter function for a given mirror length and maximum potential,
      which can be optimized in terms of ToF distribution/resolution. Such an
      optimization was performed in one- dimension (1D) by solving the ToF integral
      equation numerically. The characteristics of optimized configurations arrived at
      through a comparison with mirrors with polynomial distance-potential
      relationships are assessed. These optimised solutions cannot be approximated in
      1D by a common set of polynomial terms. There are optimised configurations
      affording ideal energy focussing, but on closer inspection, these potential
      distributions are found to be, in fact, quadratic potentials. There are other
      optimised solutions that afford good energy focussing in cases of there being
      significant field-free regions between the source/detector and the entrance to
      the mirror. Some of these configurations are approximated by a linear plus a
      quadratic term, others need higher-order terms to be approximated. To facilitate
      3D investigation, the optimised solutions in 1D were used to set the initial
      voltages on electrodes in a rotationally symmetric mirror, which was modelled
      with the computer package SIMION 8.0. The SIMION ion-flight simulations revealed
      that the other optimised solutions with higher-order terms have the disadvantage
      of lowering the transmittance. That is to say, in 3D the configurations of the
      curved field, which give good resolution and transmittance with field- free
      regions between source/detector and mirror, can all be approximated by a
      potential consisting of a linear plus a quadratic term. 

PMID- 26307693
TI  - Automated quantum chemistry based molecular dynamics simulations of electron
      ionization induced fragmentations of the nucleobases Uracil, Thymine, Cytosine,
      and Guanine.
AB  - The gas-phase decomposition pathways of electron ionization (EI)-induced radical
      cations of the nucleobases uracil, thymine, cytosine, and guanine are
      investigated by means of mixed quantum-classical molecular dynamics. No
      preconceived fragmentation channels are used in the calculations. The results
      compare well to a plethora of experimental and theoretical data for these
      important biomolecules. With our combined stochastic and dynamic approach, one
      can access in an unbiased way the energetically available decomposition
      mechanisms. Additionally, we are able to separate the EI mass spectra of
      different tautomers of cytosine and guanine. Our method (previously termed
      quantum chemistry electron ionization mass spectra) reproduces free nucleobase
      experimental mass spectra well and provides detailed mechanistic in-sight into
      high-energy unimolecular decomposition processes. 

PMID- 26307694
TI  - Computational studies of the gas phase reactions of ethers with anions: kinetic
      barriers, isotope effects, consecutive eliminations and site selectivity.
AB  - Bimolecular elimination reactions (E2) are fundamentally important processes in
      organic chemistry. Our current work focuses on a computational investigation of
      several interesting and unexpected experimental results previously obtained in
      our laboratory. In particular, we have examined the detailed mechanisms for
      generating CH(2)CHO(-) from the reaction of HO(-) + CH(3)CH(2)OCH(2)CH(2)OCH(3),
      the unusually large isotope effect (k(D)/k(H) = 5.5) for the reaction of NH(2)(-)
      + CH(3)CH(2)OCH(2)CH(3), and the possible kinetic barriers in the reaction of H(
      ) + CH(3)CH(2)OCH(2)CH(3). Moreover, we have explored the high site selectivity
      in the reaction of NH(2)(-) + CH(3)CH(2)OC(CH(3))(3). In the HO(-) +
      CH(3)CH(2)OCH(2)CH(2)OCH(3) reaction, three ion-neutral encounter complexes were
      located and fully optimized. The corresponding transition states were confirmed
      during the first E2 hydrogen-transfer process and they all possess E1(cb)-like
      antiperiplanar conformations. The formation of loosely bonded CH(3)O(-) and H(2)O
      moieties was found to be essential for the second E2-type hydrogen transfer, and
      an intriguing E1(cb)-like gauche transition state (CH(3)OH-Calpha-Cbeta- OCHCH(2)
      dihedral = 40.9 degrees ) is located, which results in the formation of ionic
      CH(2)CHO(-) and neutral CH(3)OH, H(2)O and C(2)H(4) products. The lowest kinetic
      barrier for the reaction of NH(2)(-) + CH(3)CH(2)OCH(2)CH(3) is 5.3 kcal mol(-1)
      (1 kcal mol(-1) = 4.2 kJ mol(-1)), which is 1.5 kcal mol(-1) higher in energy
      than the lowest barrier for the reaction HO(-) + CH(3)CH(2)OCH(2)CH(3). The
      higher kinetic barrier of the NH(2)(-) + CH(3)CH(2)OCH(2)CH(3) reaction is
      consistent with the observation of a larger isotope effect. The lowest kinetic
      barrier for the reaction of H(-) + CH(3)CH(2)OCH(2)CH(3) is +5.4 kcal mol(-1),
      indicating that, although H(-) is a strong base, this reaction cannot occur at
      room temperature, which agrees well with the experimental results. The high
      selectivity in the formation of CH(3)CH(2)O(-) from the reaction of NH(2)(-) +
      CH(3)CH(2)OC(CH(3))(3) is explained by an electrostatic potential analysis of the
      ether molecule. Thus, this computational study provides important insight into
      the detailed mechanisms of elimination reactions.

PMID- 26307695
TI  - Gas-phase lithium cation affinity of glycine.
AB  - The gas-phase lithium cation binding thermochemistry of glycine has been
      determined theoretically by quantum chemical calculations at the G4 level and
      experimentally by the extended kinetic method using electrospray ionization
      quadrupole time-of-flight tandem mass spectrometry. The lithium cation affinity
      of glycine, ?(Li)H degrees (298)(GLY), i.e. the?(Li)H degrees (298) of the
      reaction GlyLi(+)-> Gly + Li(+)) given by the G4 method is equal to 241.4 kJ.mol(
      1) if only the most stable conformer of glycine is considered or to 242.3 kJ.mol(
      1) if the 298K equilibrium mixture of neutral conformers is included in the
      calculation. The ?(Li)H degrees (298)(GLY) deduced from the extended kinetic
      method is obviously dependent on the choice of the Li(+) affinity scale,
      thus?(Li)H degrees (298)(GLY) is equal to 228.7+/-0.9(2.0) kJ.mol(- 1) if
      anchored to the recently re-evaluated lithium cation affinity scale but shifted
      to 235.4+/-1.0 kJ.mol(-1) if G4 computed lithium cation affinities of the
      reference molecules is used. This difference of 6.3 kJ.mol(-1) may originate from
      a compression of the experimental lithium affinity scale in the high ?(Li)H
      degrees (298) region. The entropy change associated with the reaction GlyLi(+)
      >Gly + Li(+) reveals a gain of approximately 15 J.mol(-) 1.K(-1) with respect to
      monodentate Li(+) acceptors. The origin of this excess entropy is attributed to
      the bidentate interaction between the Li(+) cation and both the carbonyl oxygen
      and the nitrogen atoms of glycine. The computed G4 Gibbs free energy,?(Li)G
      degrees (298)(GLY) is equal to 205.3 kJ.mol(-1), a similar result, 201.0+/-3.4
      kJ.mol(-1), is obtained from the experiment if the?(Li)G degrees (298) of the
      reference molecules is anchored on the G4 results.

PMID- 26307696
TI  - Dissociation mechanism of the 3-hydroxypyridine radical cation: A computational
      study.
AB  - The potential energy surface (PES) for the losses of CO and HCN from the 3
      hydroxypyridine radical cation (3-HP(+*)) and for the isomerizations to 2- and 4
      HP(+*) was determined from G3//B3LYP calculations. The overall activation
      energies are similar for six dissociation channels to form the radical cations of
      CH(2)=CHCH=N=CH, 1-H, 2-H, and 3-H pyrrole by the loss of CO and to form the
      radical cations of CH(2)=CHCH=C=O and furan by the loss of HCN. A kinetic
      analysis based on the obtained PES shows that the acyclic C(4)H(5)N(+*) and
      C(4)H(4)O(+*) ions are the main products formed by the losses of CO and HCN,
      respectively.

PMID- 26307697
TI  - Complexes of the noble gases with H3O+: a theoretical investigation on Ng(H3O+)
      (Ng = He-Xe).
AB  - The geometries, harmonic vibrational frequencies, and binding energies (Bes) of
      the Ng(H(3)O(+)) complexes (Ng = He-Xe) were investigated at the coupled cluster
      level of theory, and their bonding situation was assayed by various methods of
      bonding analysis. The effects of Ng on H(3)O(+) progressively increase from He to
      Xe, and only He can be regarded as an essentially "innocent" ligand. The binding
      energies also increase in the same periodic order, and are by far dominated by
      the "noncovalent" ion-induced dipole interaction arising from the H(3)O(+)
      induced polarization of Ng. For Ne, Ar, Kr, and Xe, this term has a larger
      contribution from the p orbital lying on the bond axis, and two smaller
      contributions from the p orbitals perpendicular to the bond axis. For the
      heaviest Ar(H(3)O(+)), Kr(H(3)O(+)), and Xe(H(3)O(+)), BE also has a "covalent"
      component, which is ascribed to the relatively-appreciable charge transfer from
      Ng to H(3)O(+).

PMID- 26307698
TI  - Mass spectrometry of analytical derivatives. 1. Cyanide cations in the spectra of
      N- alkyl-N-perfluoroacyl- alpha-amino acids and their methyl esters.
AB  - The central mission for the development of the National Institute of Standards
      and Technology/National Institutes of Health/Environmental Protection Agency Mass
      Spectral Library is the acquisition of reference gas chromatography-mass
      spectrometry data for important compounds and their chemical modification
      products. The addition of reliable reference data of various derivatives of amino
      acids to The Library, and the study of their behavior under electron ionization
      conditions may be useful for their identification, structure elucidation and a
      better understanding of the data obtained when the same derivatives are subjected
      to other ionization methods. N-Alkyl-N-perfluoroacyl derivatives of amino acids
      readily produce previously unreported alkylnitrilium cations of composition [HC=N
      alkyl](+). Homologous [HC=N-aryl](+) cations are typical for corresponding N-aryl
      analogs. The formation of other ions characteristic for these derivatives
      involves oxygen rearrangement giving rise to ions [C(n)F(2n+1)-C=N(+)C(n)H(2n+1)]
      and [CnF(2n+1)-C=N(+)-aryl]. The introduction of an N-benzyl substituent in a
      molecule favors a process producing benzylidene iminium cations. L-Threonine and
      L-cysteine derivatives exhibit more fragmentation pathways not typical for other
      alpha-amino acids; additionally, the N(omega)- amino group in L-lysine directs
      the dissociation process and provides structural information on the substitution
      at the amino functions in the molecule.

PMID- 26307699
TI  - Separation and identification of phosphatidylcholine regioisomers by combining
      liquid chromatography with a fusion of collision-and ozone-induced dissociation.
AB  - The differentiation of closely related lipid isomers is increasingly important to
      our evolving understanding of lipid biochemistry but it is equally challenging to
      contemporary chromatographic and mass spectral analyses. Recently, we described a
      novel ion-activation approach based on combining collision- with ozone-induced
      dissociation (CID/OzID) for the identification of the relative acyl chain
      substitution positions in glycerophospholipids. Here we demonstrate, for the
      first time, that CID/OzID can be effectively combined with reversed-phase
      chromatography to enable the separation and unambiguous identification of
      regioisomeric pairs of phosphatidylcholines that differ only in the arrangement
      of acyl chains on the glycerol backbone. 

PMID- 26307700
TI  - Drug detection and quantification directly from tissue using novel ionization
      methods for mass spectrometry.
AB  - Solvent assisted ionization inlet (SAII) and matrix assisted ionization vacuum
      (MAIV) were used to quantify rapidly an antipsychotic drug, clozapine, directly
      from surfaces with minimal sample preparation. This simple surface analysis
      method based on SAII- and MAIV-mass spectrometry (MS) was developed to allow the
      detection of endogenous lipids, metabolites, and clozapine directly from sections
      of mouse brain tissue. A rapid surface assessment was achieved by SAII with the
      assistance of heat applied to the mass spectrometer inlet. MAIV provided an
      improved reproducibility without the need of a heated inlet. In addition, isotope
      dilution and standard addition were used without sample clean-up, and the results
      correlate well with liquid chromatography tandem MS using sample work-up. Using
      the simple surface methods, standard solutions containing clozapine and a
      deuterated internal standard (clozapine-d8) at different concentration ratios
      were used in the extraction and quantification of clozapine from brain tissue
      sections of a drug-treated mouse using different tissue thicknesses. The amount
      of clozapine extracted by these surface methods was independent of tissue
      thickness. 

PMID- 26307701
TI  - Structural characterization of arginine-vasopressin and lysine-vasopressin by
      Fourier- transform ion cyclotron resonance mass spectrometry and infrared
      multiphoton dissociation.
AB  - Arginine-vasopressin (AVP) and lysine-vasopressin (LVP) were analyzed by reversed
      phase liquid chromatography/mass spectrometry (LC-MS) using Fourier-transform ion
      cyclotron resonance (FT-ICR) mass spectrometry (MS) electrospray ionization (ESI)
      in the positive ion mode. LVP and AVP exhibited the protonated adduct [M+H](+) as
      the predominant ion at m/z 1056.43965 and at m/z 1084.44561, respectively.
      Infrared multiphoton dissociation (IRMPD), using a CO(2) laser source at a
      wavelength of 10.6 MUm, was applied to protonated vasopressin molecules. The
      IRMPD mass spectra presented abundant mass fragments essential for a complete
      structural information. Several fragment ions, shared between two target
      molecules, are discussed in detail. Some previously unpublished fragments were
      identified unambiguously utilizing the high resolution and accurate mass
      information provided by the FT-ICR mass spectrometer. The opening of the
      disulfide loop and the cleavage of the peptide bonds within the ring were
      observed even under low-energy fragmentation conditions. Coupling the high
      performance FT-ICR mass spectrometer with IRMPD as a contemporary fragmentation
      technique proved to be very promising for the structural characterization of
      vasopressin.

PMID- 26307703
TI  - Glycated human serum albumin isolated from poorly controlled diabetic patients
      impairs cholesterol efflux from macrophages: an investigation by mass
      spectrometry.
AB  - Advanced glycation end-products impair ABCA-1-mediated cholesterol efflux by
      eliciting inflammation, the generation of reactive oxygen species and
      endoplasmatic reticulum (ER) stress. The glycation level of human serum albumin
      (HSA) from type 1 and type 2 diabetic patients was determined by matrix assisted
      laser desorption/ionization (MALDI) mass spectrometry and related to possible
      impairment of ER function and cellular cholesterol efflux. Comparison of the
      MALDI spectra from healthy and diabetic subjects allowed us to determine an
      increased HSA mean mass of 1297 Da for type 1 and 890 Da for type 2. These values
      reflect a mean condensation of at least 8 glucose units and 5 glucose units,
      respectively. Mouse peritoneal macrophages were treated with HSA from control,
      type 1 and type 2 diabetic subjects in order to measure the expression of Grp78,
      Grp94, protein disulfide isomerase (PDI), calreticulin (CRT) and ABCA-1. (14)C
      cholesterol overloaded-J774 macrophages were treated with HSA from control and
      diabetic subjects and further incubated with apo A-1 to determine the cholesterol
      efflux. Combined analyses comprising HSA from type 1 and type 2 diabetic patients
      were performed in cellular functional assays. In macrophages, PDI expression
      increased 89% and CRT 3.4 times in comparison to HSA from the control subjects.
      ABCA-1 protein level and apo A-I mediated cholesterol efflux were, respectively,
      50% and 60% reduced in macrophages exposed to HSA from type 1 and type 2 diabetic
      patients when compared to that exposed to HSA from control subjects. We provide
      evidence that the level of glycation that occurs in albumin in vivo damages the
      ER function related to the impairment in macrophage reverse cholesterol transport
      and so contributes to atherosclerosis in diabetes. 

PMID- 26307702
TI  - Native top-down mass spectrometry for the structural characterization of human
      hemoglobin.
AB  - Native mass spectrometry (MS) has become an invaluable tool for the
      characterization of proteins and noncovalent protein complexes under near
      physiological solution conditions. Here we report the structural characterization
      of human hemoglobin (Hb), a 64 kDa oxygen-transporting protein complex, by high
      resolution native top-down MS using electrospray ionization and a 15-Tesla
      Fourier transform ion cyclotron resonance mass spectrometer. Native MS preserves
      the noncovalent interactions between the globin subunits, and electron capture
      dissociation (ECD) produces fragments directly from the intact Hb complex without
      dissociating the subunits. Using activated ion ECD, we observe the gradual
      unfolding process of the Hb complex in the gas phase. Without protein ion
      activation, the native Hb shows very limited ECD fragmentation from the N
      termini, suggesting a tightly packed structure of the native complex and
      therefore a low fragmentation efficiency. Precursor ion activation allows a
      steady increase in N-terminal fragment ions, while the C-terminal fragments
      remain limited (38 c ions and four z ions on the alpha chain; 36 c ions and two z
      ions on the beta chain). This ECD fragmentation pattern suggests that upon
      activation, the Hb complex starts to unfold from the N-termini of both subunits,
      whereas the C-terminal regions and therefore the potential regions involved in
      the subunit binding interactions remain intact. ECD-MS of the Hb dimer shows
      similar fragmentation patterns as the Hb tetramer, providing further evidence for
      the hypothesized unfolding process of the Hb complex in the gas phase. Native top
      down ECD-MS allows efficient probing of the Hb complex structure and the subunit
      binding interactions in the gas phase. It may provide a fast and effective means
      to probe the structure of novel protein complexes that are intractable to
      traditional structural characterization tools.

PMID- 26307704
TI  - Composition, sequencing and ion mobility mass spectrometry of heparan sulfate
      like octasaccharide isomers differing in glucuronic and iduronic acid content.
AB  - Here we report ion mobility mass spectrometry (IMMS) separation and tandem mass
      spectrometry (MS(2)) sequencing methods used to analyze and differentiate six
      synthetically produced heparin/heparan sulfate (HS)-like octasaccharide (dp8)
      isomeric structures. These structures are isomeric with regard to either
      glucuronic acid (GlcA) or iduronic acid (IdoA) residues at various positions.
      IMMS analysis showed that a fully GlcA structure exhibited a more compact
      conformation, whereas the fully IdoA structure was more extended. Interestingly,
      the change from IdoA to GlcA in specific locations resulted in strong
      conformational distortions. MS(2) of the six isomers showed very different
      spectra with unique sets of diagnostic product ions. Analysis of MS(2) product
      ion spectra suggests that the GlcA group correlated with the formation of a
      glycosidic product ion under lower energy conditions. This resulted in an earlier
      product ion formation and more intense product ions. Importantly, this knowledge
      enabled a complete sequencing of the positions of GlcA and IdoA in each of the
      four positions located in each unique dp8 structure. 

PMID- 26307705
TI  - Ion mobility-mass spectrometry-based screening for inhibition of alpha- synuclein
      aggregation.
AB  - Aberrant protein folding and formation of amyloid fibrils are associated with
      numerous debilitating human diseases, for which there are currently no suitable
      therapeutic treatments. For instance, Parkinson's disease is characterised
      pathologically by the intraneural accumulation of the amyloid protein alpha-
      synuclein. In order to search for new therapeutic agents that are effective in
      preventing the early conformational changes that precede protein aggregation, it
      is necessary to devise new analytical screening approaches. Here we demonstrate
      the use of ion mobility-mass spectrometry for screening of molecules capable of
      inhibiting the misfolding and aggregation of alpha-synuclein (specifically, the
      A53T human mutant). Importantly, this assay allows for the analysis of
      conformational changes that precede aggregation, and therefore is unique in its
      ability to identify inhibitors working at the earliest stages of amyloid
      formation. In addition, we use complementary mass spectrometry methods to probe
      selected protein-ligand interactions responsible for fibril inhibition. 

PMID- 26307706
TI  - Analysis of triacetone triperoxide complexes with alkali metal ions by
      electrospray and extractive electrospray ionisation combined with ion mobility
      spectrometry and mass spectrometry.
AB  - The complexation of triacetone triperoxide (TATP) with a range of alkali metals
      has been studied by electrospray ionisation-mass spectrometry yield [M+Cat](+)
      ions for all of the alkali metals. The formation of [2TATP+Li+LiX](+) (X = Br,
      Cl) sandwich complexes was also observed. Collision cross- sections for the
      lithium-containing complexes of TATP were measured by travelling wave ion
      mobility spectrometry mass spectrometry, and compared well with computationally
      determined structures. Extractive electrospray ionisation (EESI) using a lithium
      doped electrospray is demonstrated for the detection of TATP vapours desorbed
      from a metal surface. The limit of detection for EESI was shown to be 20 ng using
      the [TATP+Li](+) ion. 

PMID- 26307707
TI  - Differentiating chondroitin sulfate glycosaminoglycans using collision-induced
      dissociation; uronic acid cross-ring diagnostic fragments in a single stage of
      tandem mass spectrometry.
AB  - The stereochemistry of the hexuronic acid residues of the structure of
      glycosaminoglycans (GAGs) is a key feature that affects their interactions with
      proteins and other biological functions. Electron based tandem mass spectrometry
      methods, in particular electron detachment dissociation (EDD), have been able to
      distinguish glucuronic acid (GlcA) from iduronic acid (IdoA) residues in some
      heparan sulfate tetrasaccharides by producing epimer-specific fragments.
      Similarly, the relative abundance of glycosidic fragment ions produced by
      collision-induced dissociation (CID) or EDD has been shown to correlate with the
      type of hexuronic acid present in chondroitin sulfate GAGs. The present work
      examines the effect of charge state and degree of sodium cationization on the CID
      fragmentation products that can be used to distinguish GlcA and IdoA containing
      chondroitin sulfate A and dermatan sulfate chains. The cross-ring fragments
      (2,4)A(n) and (0,2)X(n) formed within the hexuronic acid residues are highly
      preferential for chains containing GlcA, distinguishing it from IdoA. The
      diagnostic capability of the fragments requires the selection of a molecular ion
      and fragment ions with specific ionization characteristics, namely charge state
      and number of ionizable protons. The ions with the appropriate characteristics
      display diagnostic properties for all the chondroitin sulfate and dermatan
      sulfate chains (degree of polymerization of 4-10) studied.

PMID- 26307708
TI  - Photoinduced intermolecular cross-linking of gas phase triacylglycerol lipid
      ions.
AB  - Complex mixtures of plant derived triglycerol (TG) lipids are commonly used as
      feedstock components for the production of industrial polymers. However, there
      remains a need for the development of analytical strategies to investigate the
      intrinsic intermolecular cross-linking reactivity of individual TG molecules
      within these mixtures as a function of their structures and physicochemical
      properties, and for the characterization of the resultant products. Here, to
      address this need, we describe a novel multistage tandem mass spectrometry based
      method for intermolecular cross-linking and subsequent structural
      characterization of TG lipid ions in the gas phase. Cross-linking reactions were
      initiated using 266 nm ultraviolet photodissociation tandem mass spectrometry
      (UVPD-MS/MS) of saturated or unsaturated TG dimers introduced via electrospray
      ionization into a linear ion trap mass spectrometer as noncovalent complexes with
      protonated 3,4-, 2,4- or 3,5- diiodoaniline (diIA). UVPD resulted in the initial
      formation of an anilinyl biradical via the sequential loss of two iodine
      radicals, which underwent further reaction to yield multiple cross-linked TG
      products along with competing noncross-linking processes. These chemistries are
      proposed to occur via sequential combinations of hydrogen abstraction (H
      abstraction), radical addition and radical recombination. Multistage collision
      induced dissociation tandem mass spectrometry (CID-MS(n)) was used to obtain
      evidence for the structures and mechanisms of formation for these products, as a
      function of both the TG lipid and diIA ion structures. The efficiency of the UVPD
      reaction was shown to be dependent on the number of unsaturation sites present
      within the TG lipids. However, when unsaturation sites were present, formation of
      the cross-linked and noncross-linked product ions via H-abstraction and radical
      addition mechanisms was found to be competitive. Finally, the identity of the
      anilinyl biradical (e.g., 3,4- versus 2,4-substituted) was found to significantly
      affect the distribution of these two types of product ions. Importantly, owing to
      the observed propensity for cross-linking to occur via H-abstraction-initiated
      processes, this novel gas-phase cross-linking reaction provides a convenient
      method to link two molecules covalently without the requirement of any specific
      functional group, and therefore could be applied to examine the gas-phase
      intermolecular interactions and cross-linking of a wide range of biomolecular
      classes. 

PMID- 26307709
TI  - Age-related changes in the lateral lipid distribution in a human lens described
      by mass spectrometry imaging.
AB  - The lateral lipid distribution in eye lenses of three human donors were studied
      by matrix-assisted laser desorption ionization imaging mass spectrometry using a
      high mass resolution. By using exact mass measurements this study shows the
      relationship between the aging process and the number of lipids detected as well
      as between aging and the abundance of products derived from sphingomyelins by
      hydrolysis. Variable lipid composition was also observed in the nuclear, barrier,
      or cortex regions of the lens samples. This is the first study that suggests the
      distribution of lysolipids as a potential biomarker panel for the aging of human
      lens tissue. 

PMID- 26307710
TI  - Direct gas-phase detection of nerve and blister warfare agents utilizing active
      capillary plasma ionization mass spectrometry.
AB  - Ultrasensitive direct gas-phase detection of chemical warfare agents (CWAs) is
      demonstrated utilizing active capillary plasma ionization and triple quadrupole
      mass spectrometry (MS) instrumentation. Four G- agents, two V-agents and various
      blistering agents [including sulfur mustard (HD)] were detected directly in the
      gas phase with limits of detection in the low parts per trillion (ng m(-3))
      range. The direct detection of HD was shown for dry carrier gas conditions, but
      signals vanished when humidity was present, indicating a possible direct
      detection of HD after sufficient gas phase pretreatment. The method provided
      sufficient sensitivity to monitor directly the investigated volatile CWAs way
      below their corresponding minimal effect dose, and in most cases even below the
      eight hours worker exposure concentration. In general, the ionization is very
      soft, with little to no in-source fragmentation. Especially for the G-agents,
      some dimer formation occurred at higher concentrations. This adds complexity, but
      also further selectivity, to the corresponding mass spectra. Our results show
      that the active capillary plasma ionization is a robust, sensitive, "plug and
      play" ambient ionization source suited (but not exclusively) to the very
      sensitive detection of CWAs. It has the potential to be used with portable MS
      instrumentation. 

PMID- 26307711
TI  - Polydimethylsiloxane extraction from silicone rubber into baked goods detected by
      direct analysis in real time mass spectrometry.
AB  - Flexible baking molds and other household utensils are made of
      polydimethylsiloxane (PDMS), also known as silicone rubber. PDMS is prone to
      release oligomers upon elongated contact with fats, e.g., in the process of
      baking dough. Positive-ion direct analysis in real time (DART) mass spectrometry
      (MS) provides an efficient tool for the analysis of PDMS up to m/z 3000. Here,
      DART ionization is employed in combination with Fourier transform ion cyclotron
      resonance MS to detect PDMS released into muffins when baked in silicone rubber
      baking molds. Intensive signals caused by PDMS do occur in the m/z 700-1500 range
      of DART mass spectra obtained from the crusty surface of muffins after the use of
      such silicone rubber molds. In addition, triacylglyceroles (TAGs) present as
      natural ingredients of the analyzed muffins were detected as [TAG+NH(4)](+) ions.

PMID- 26307713
TI  - Probe electrospray ionization (PESI) mass spectrometry with discontinuous
      atmospheric pressure interface (DAPI).
AB  - Probe electrospray ionization (PESI) using a 0.2 mm outside diameter titanium
      wire was performed and the generated ions were introduced into the mass
      spectrometer via a discontinuous atmospheric pressure interface using a pinch
      valve. Time-lapse PESI mass spectra were acquired by gradually increasing delay
      time for the pinch valve opening with respect to the start of each electrospray
      event when a high voltage was applied. The opening time of the pinch valve was 20
      ms. Time-resolved PESI mass spectra showed marked differences for 10 mM NaCl, 10(
      5) M gramicidin S and insulin in H(2)O/CH(3)OH/CH(3)COOH/CH(3)COONH(4) (65/35/1)
      with and without the addition of 10 mM CH(3)COONH(4). This was ascribed to the pH
      change of the liquid attached to the needle caused by electrochemical reactions
      taking place at the interface between the metal probe and the solution. NaCl
      cluster ions appeared only after the depletion of analytes. For the mixed
      solution of 10(-5) M cytochrome c, insulin, and gramicidin S in
      H(2)O/CH(3)OH/CH(3)COOH (65/35/1), a sequential appearance of analyte ions in the
      order of cytochrome c->insulin->gramicidin S was observed. The present technique
      was applied to three narcotic samples; methamphetamine, morphine and codeine.
      Limits of detection for these compounds were 10 ppb in H(2)O/CH(3)OH (1/1) for
      the single sampling with a pinch valve opening time of 200 ms.

PMID- 26307712
TI  - Mass spectrometric studies of fast pyrolysis of cellulose.
AB  - A fast pyrolysis probe/linear quadrupole ion trap mass spectrometer combination
      was used to study the primary fast pyrolysis products (those that first leave the
      hot pyrolysis surface) of cellulose, cellobiose, cellotriose, cellotetraose,
      cellopentaose, and cellohexaose, as well as of cellobiosan, cellotriosan, and
      cellopentosan, at 600 degrees C. Similar products with different branching ratios
      were found for the oligosaccharides and cellulose, as reported previously.
      However, identical products (with the exception of two) with similar branching
      ratios were measured for cellotriosan (and cellopentosan) and cellulose. This
      result demonstrates that cellotriosan is an excellent small-molecule surrogate
      for studies of the fast pyrolysis of cellulose and also that most fast pyrolysis
      products of cellulose do not originate from the reducing end. Based on several
      observations, the fast pyrolysis of cellulose is suggested to initiate
      predominantly via two competing processes: the formation of anhydro
      oligosaccharides, such as cellobiosan, cellotriosan, and cellopentosan (major
      route), and the elimination of glycolaldehyde (or isomeric) units from the
      reducing end of oligosaccharides formed from cellulose during fast pyrolysis. 

PMID- 26307714
TI  - Determination of traces of uranium and thorium in titanium and copper used for
      the construction of the Russian Emission Detector 100 by inductively coupled
      plasma mass spectrometry.
AB  - The Russian Emission Detector 100 (RED-100) under construction at the National
      Research Nuclear University MEPhI (Moscow Engineering Physics Institute) is
      designed to detect the presently undiscovered effect of coherent neutrino
      scattering. One of the factors limiting the sensitivity of the detector is the
      spontaneous decay of uranium and thorium in the detector materials. Radioactive
      impurities in detector materials at levels of parts per billion can significantly
      affect the sensitivity. Five random samples of titanium and one of copper from
      materials used in the construction of the detector were selected for assay. The
      concentration of (232)Th and (238)U were measured by inductively coupled plasma
      mass spectrometry (ICP- MS) in solid titanium using both: solutions in acids and
      direct sampling by laser ablation (LA-ICP-MS). The LA- ICP-MS method allowed us
      to determine (238)U and (232)Th at subnanogram per gram levels. This method is
      much faster than ICP-MS with liquid injection. The titanium samples studied have
      impurities in the range between 1 ng g(-1) and 21 ng g(-1) for (238)U and 3 ng g(
      1) and 31 ng g(-1) for (232)Th. In copper we set upper limits of 0.4 ng g(-1) for
      (238)U and 1 ng g(-1)for (232)Th. The total activity of the cryostat constructed
      from materials studied was estimated to be 43 Bq.

PMID- 26307716
TI  - Electrospray mass spectrometry with controlled in-source atomization (ERIAD) as a
      promising elemental method: evaluation of analytical features.
AB  - Electrospray ionization with controlled in-source fragmentation and atomization
      (ERIAD) is promising method for mass-spectrometric elemental analysis. This paper
      concerns the main analytical features and necessary instrumentation for ERIAD.
      The method is shown to be effective for more than 70 elements of the periodic
      table: those that present as cations in a water solution. It shows a high
      absolute sensitivity with a low spread from Li to U, and a detection limit of
      tens of parts per trillion. The soft ionization used results in the absence of
      plasma chemical reaction products, typical for inductively coupled plasma mass
      spectrometry, and the spectra are nearly free from interferences. The method does
      not require a high resolution and can be used for samples with an artificial
      isotopic content. The method is essentially valid for radiochemistry and
      metallomics, as it has the possibility to combine measurements of chemical,
      elemental, and even isotopic content simultaneously. 

PMID- 26307717
TI  - Reversed phase liquid chromatography hyphenated to continuous flow-extractive
      desorption electrospray ionization-mass spectrometry for analysis and charge
      state manipulation of undigested proteins.
AB  - The application of continuous flow-extractive desorption electrospray ionization
      (CF-EDESI), an ambient ionization source demonstrated previously for use with
      intact protein analysis, is expanded here for the coupling of reversed phase
      protein separations to mass spectrometry. This configuration allows the
      introduction of charging additives to enhance detection without affecting the
      chromatographic separation mechanism. Two demonstrations of the advantages of CF
      EDESI are presented in this work. First, a proof-of- principle is presented to
      demonstrate the applicability of hyphenation of liquid chromatography (LC) to CF-
      EDESI. LC-CF-EDESI-MS has good sensitivity compared to LC-electrospray ionization
      (ESI)-mass spectrometry. Second, the supercharging mechanism investigated in CF
      EDESI provides an insight into a highly debated supercharging process in ESI. The
      results indicate that the mechanism of protein charging seen in HPLC-CF-EDESI is
      different from supercharging phenomena in conventional ESI. The surface tension
      mechanism and binding mechanism may both contribute to protein supercharging in
      ESI. 

PMID- 26307715
TI  - Integration of electrochemistry with ultra-performance liquid chromatography/mass
      spectrometry.
AB  - This study presents the development of ultra-performance liquid chromatography
      (UPLC) mass spectrometry (MS) combined with electrochemistry (EC) for the first
      time and its application for the structural analysis of proteins/peptides that
      contain disulfide bonds. In our approach, a protein/peptide mixture sample
      undergoes a fast UPLC separation and subsequent electrochemical reduction in an
      electrochemical flow cell followed by online MS and tandem mass spectrometry
      (MS/MS) analyses. The electrochemical cell is coupled to the mass spectrometer
      using our recently developed desorption electrospray ionization (DESI) interface.
      Using this UPLC/EC/DESI-MS method, peptides that contain disulfide bonds can be
      differentiated from those without disulfide bonds, as the former are
      electroactive and reducible. MS/MS analysis of the disulfide-reduced peptide ions
      provides increased information on the sequence and disulfide-linkage pattern. In
      a reactive DESI- MS detection experiment in which a supercharging reagent was
      used to dope the DESI spray solvent, increased charging was obtained for the UPLC
      separated proteins. Strikingly, upon online electrolytic reduction, supercharged
      proteins (e.g., alpha-lactalbumin) showed even higher charging, which will be
      useful in top- down protein structure MS analysis as increased charges are known
      to promote protein ion dissociation. Also, the separation speed and sensitivity
      are enhanced by approximately 1(~)2 orders of magnitude by using UPLC for the
      liquid chromatography (LC)/EC/MS platform, in comparison to the previously used
      high- performance liquid chromatography (HPLC). This UPLC/EC/DESI-MS method
      combines the power of fast UPLC separation, fast electrochemical conversion, and
      online MS structural analysis for a potentially valuable tool for proteomics
      research and bioanalysis. 

PMID- 26307719
TI  - Surface-induced dissociation: a unique tool for studying energetics and kinetics
      of the gas-phase fragmentation of large ions.
AB  - Surface-induced dissociation (SID) is a valuable tool for investigating the
      activation and dissociation of large ions in tandem mass spectrometry. This
      account summarizes key findings from studies of the energetics and mechanisms of
      complex ion dissociation in which SID experiments were combined with Rice
      Ramsperger-Kassel-Marcus modeling of the experimental data. These studies used
      time- and collision-energy-resolved SID experiments and SID combined with
      resonant ejection of selected fragment ions on a specially designed Fourier
      transform ion cyclotron resonance (FT-ICR) mass spectrometer. Fast-ion activation
      by collision with a surface combined with the long and variable timescale of FT
      ICR mass spectrometry is perfectly suited to studying the energetics and dynamics
      of complex ion dissociation in the gas phase. Modeling of time- and collision
      energy-resolved SID enables the accurate determination of energy and entropy
      effects in the dissociation process. It has been demonstrated that entropy
      effects play an important role in determining the dissociation rates of both
      covalent and noncovalent bonds in large gaseous ions. SID studies have provided
      important insights on the competition between charge-directed and charge-remote
      fragmentation in even-electron peptide ions and the role of the charge and
      radical site on the energetics of the dissociation of odd-electron peptide ions.
      Furthermore, this work examined factors that affect the strength of noncovalent
      binding, as well as the competition between covalent and noncovalent bond
      cleavages and between proton and electron transfer in model systems. Finally, SID
      studies have been used to understand the factors affecting nucleation and growth
      of clusters in solution and in the gas phase. 

PMID- 26307718
TI  - A new liquid chromatography-mass spectrometry-based method to quantitate
      exogenous recombinant transferrin in cerebrospinal fluid: a potential approach
      for pharmacokinetic studies of transferrin-based therapeutics in the central
      nervous systems.
AB  - Transferrin (Tf) is an 80 kDa iron-binding protein that is viewed as a promising
      drug carrier to target the central nervous system as a result of its ability to
      penetrate the blood-brain barrier. Among the many challenges during the
      development of Tf-based therapeutics, the sensitive and accurate quantitation of
      the administered Tf in cerebrospinal fluid (CSF) remains particularly difficult
      because of the presence of abundant endogenous Tf. Herein, we describe the
      development of a new liquid chromatography-mass spectrometry-based method for the
      sensitive and accurate quantitation of exogenous recombinant human Tf in rat CSF.
      By taking advantage of a His-tag present in recombinant Tf and applying Ni
      affinity purification, the exogenous human serum Tf can be greatly enriched from
      rat CSF, despite the presence of the abundant endogenous protein. Additionally,
      we applied a newly developed (18)O-labeling technique that can generate internal
      standards at the protein level, which greatly improved the accuracy and
      robustness of quantitation. The developed method was investigated for linearity,
      accuracy, precision, and lower limit of quantitation, all of which met the
      commonly accepted criteria for bioanalytical method validation.

PMID- 26307720
TI  - An electrospray ionization-ion mobility spectrometer as detector for high-
      performance liquid chromatography.
AB  - The application of electrospray ionization (ESI) ion mobility (IM) spectrometry
      on the detection end of a high-performance liquid chromatograph has been a
      subject of study for some time. So far, this method has been limited to low flow
      rates or has required splitting of the liquid flow. This work presents a novel
      concept of an ESI source facilitating the stable operation of the spectrometer at
      flow rates between 10 MUL mn(-1) and 1500 MUL min(-1) without flow splitting,
      advancing the T-cylinder design developed by Kurnin and co-workers. Flow rates
      eight times faster than previously reported were achieved because of a more
      efficient dispersion of the liquid at increased electrospray voltages combined
      with nebulization by a sheath gas. Imaging revealed the spray operation to be in
      a rotationally symmetric multijet mode. The novel ESI-IM spectrometer tolerates
      high water contents (<=90%) and electrolyte concentrations up to 10mM, meeting
      another condition required of high-performance liquid chromatography (HPLC)
      detectors. Limits of detection of 50 nM for promazine in the positive mode and 1
      MUM for 1,3-dinitrobenzene in the negative mode were established. Three mixtures
      of reduced complexity (five surfactants, four neuroleptics, and two isomers) were
      separated in the millisecond regime in stand-alone operation of the spectrometer.
      Separations of two more complex mixtures (five neuroleptics and 13 pesticides)
      demonstrate the application of the spectrometer as an HPLC detector. The examples
      illustrate the advantages of the spectrometer over the established diode array
      detector, in terms of additional IM separation of substances not fully separated
      in the retention time domain as well as identification of substances based on
      their characteristic Ims.

PMID- 26307721
TI  - Reactive matrices for matrix-assisted laser desorption/ionization mass
      spectrometry of primary amines.
AB  - Some aromatic carbonyl compounds [2,4-dihydroxybenzaldehyde (2,4-DHBA), 2,5-
      dihydroxyacetophenone (DHAP), 2,3,5-trihydroxybenzaldehyde and 2,4
      dinitrobenzaldehyde] were examined as potential reactive matrices for the
      analysis of mono-, di-, and polyamines by matrix-assisted laser
      desorption/ionization (MALDI) mass spectrometry (MS). Although all the above
      compounds readily and quantitatively react with primary amines to form Schiff
      bases (the completeness of the reactions was proved by gas chromatography MS of
      derivatized aliphatic amines), only DHBA and DHAP provide efficient
      desorption/ionization under MALDI conditions. This means that two these aromatic
      carbonyl compounds can simultaneously exhibit properties of both derivatization
      agents and efficient matrices for MALDI-MS analysis. The use of such reactive
      matrices eliminates the need to perform additional derivatization experiments.
      With the aid of DHBA and DHAP, it was confirmed that each individual oligomer of
      polypropylene glycols and co- polyethylene/propylene glycols contained two
      terminal amino groups. To calculate the number of NH2 groups, mass increments of
      the introduced groups and a difference in the masses of cations attached to the
      initial and derivatized amines were used. The suggested approach, involving the
      application of the same reactive matrices, was applied to the determination of a
      number of NH(2) groups in individual oligomers of branched polyethyleneimines
      (PEIs) by MALDI-MS. In this case, DHAP appeared to be the best reactive matrix.
      The dependence of the number of NH(2) groups on the quantity of monomeric units
      and branching of each individual PEI oligomer is shown.

PMID- 26307722
TI  - Laser desorption ionization of stilbenes in crystalline sponge.
AB  - The laser desorption (LD) ionization of three stilbenes in the nano porous metal
      organic frameworks called "crystalline sponge" is demonstrated. The analyte
      position in the pore and the interaction between the analyte and the framework
      that functions as a matrix are discussed based on the results of single- crystal
      X-ray analysis. It is confirmed that the analyte/ligand ratio of 1:2 is
      sufficient for the analyte ionization. This method makes it possible to visualize
      hot spots on a target plate to be irradiated. That the sample requirement is
      dramatically reduced to the order of femtomoles is also an advantage. The
      relationship between laser interaction, analyte position in the pore, and
      analyte/ligand ratio is discussed as a new ionization field to elucidate the
      molecular structure of the analyte by LD ionization mass spectrometry. 

PMID- 26307723
TI  - How to deal with the "matrix effect" as an unavoidable phenomenon.
AB  - Adsorption effects in the chromatographic system and/or ion source may play a
      very important role in the ionization processes of liquid chromatography/mass
      spectrometry. They have been illustrated and considered as matrix effects
      extensively. These effects cannot be simply removed by any thorough cleaning of
      the system and/or by perfecting the chromatography. The use of isotopically
      labeled internal standards (isotope dilution technique) is the only effective
      compensation for their negative impacts. The complete effectiveness of the method
      was presented by the evaluation of normalized matrix factor (according to the
      European Medicines Agency) in 85 different high-performance liquid chromatography
      tandem mass spectrometry methods for determination of drugs in human plasma. On
      the other hand, the adsorption effect of methylamine was successfully used for
      the determination of lacidipine in human plasma at the low picogram level. 

PMID- 26307724
TI  - Application of positive mode atmospheric chemical ionisation to distinguish
      epimeric oleanolic and ursolic acids.
AB  - A new and more reliable method is reported for distinguishing the equatorial and
      axial epimers of oleanolic and ursolic acids and related triterpenoids based
      primarily on the relative abundance of the [M+H](+) and [M+-H(2)O](+) signals in
      their positive mode atmospheric pressure chemical ionisation mass spectra. The
      rate of elimination of water, which is the principal primary fragmentation of
      protonated oleanolic and ursolic acids, depends systematically on the
      stereochemistry of the hydroxyl group in the 3 position. For the b-epimer, in
      which the 3-hydroxyl substituent is in an equatorial position,[M+-H(2)O](+) is
      the base peak. In contrast, for the alpha-epimer, where the 3-hydroxyl group is
      axial, [M + H](+) is the base peak. This trend, which is general for a range of
      derivatives of oleanolic and ursolic acids, including the corresponding methyl
      esters, allows epimeric triterpenoids in these series to be securely
      differentiated. Confirmatory information is available from the collision-induced
      dissociation of the [M+-H(2)O](+) primary fragment ions, which follow different
      pathways for the species derived from axial and equatorial epimers of oleanolic
      and ursolic acids. These two pieces of independent spectral information permit
      the stereochemistry of epimeric oleanolic and ursolic acids (and selected
      derivatives) to be assigned with confidence without relying either on
      chromatographic retention times or referring to the spectra or other properties
      of authentic samples of these triterpenoids.

PMID- 26307725
TI  - Effect of magnetic field inhomogeneity on ion cyclotron motion coherence at high
      magnetic field.
AB  - A three-dimensional code based on the particle-in-cell algorithm modified to
      account for the inhomogeneity of the magnetic field was applied to determine the
      effect of Z(1), Z(2), Z(3), Z(4), X, Y, ZX, ZY, XZ(2) YZ(2), XY and X(2)-Y(2)
      components of an orthogonal magnetic field expansion on ion motion during
      detection in an FT-ICR cell. Simulations were performed for magnetic field
      strengths of 4.7, 7, 14.5 and 21 Tesla, including experimentally determined
      magnetic field spatial distributions for existing 4.7 T and 14.5 T magnets. The
      effect of magnetic field inhomogeneity on ion cloud stabilization ("ion
      condensation") at high numbers of ions was investigated by direct simulations of
      individual ion trajectories. Z(1), Z(2), Z(3) and Z(4) components have the
      largest effect (especially Z(1)) on ion cloud stability. Higher magnetic field
      strength and lower m/z demand higher relative magnetic field homogeneity to
      maintain cloud coherence for a fixed time period. The dependence of mass
      resolving power upper limit on Z(1) inhomogeneity is evaluated for different
      magnetic fields and m/z. The results serve to set the homogeneity requirements
      for various orthogonal magnetic field components (shims) for future FT-ICR magnet
      design. 

PMID- 26307726
TI  - On the use of electron capture rate constants to describe electron capture
      dissociation mass spectrometry of peptides.
AB  - Electron capture dissociation (ECD) tandem mass spectrometry (MS/MS) is a
      powerful analytical tool for peptide and protein structure analysis. The product
      ion abundance (PIA) distribution in ECD MS/MS is known to vary as a function of
      electron irradiation period. This variation complicates the development of a
      method of peptide identification by correlation of ECD MS/MS data with
      experimental and theoretical mass spectra. Here, we first develop a kinetic model
      to describe primary electron capture by peptide dications leading to product ion
      formation and secondary electron capture resulting in product ion neutralization.
      We apply the developed kinetic model to calculate product ion formation rate
      constants and electron capture rate constants of product ions from ECD mass
      spectra acquired using various electron irradiation periods. Contrary to ECD PIA
      distributions, the product ion formation rate constants are shown to be
      independent of electron irradiation period and, thus, may be employed to
      characterize ECD product ion formation more universally. The electron capture
      rate constants of product ions in ECD Fourier transform ion cyclotron resonance
      MS were found to correlate (with a correlation factor, R(2), of ca 0.9) with ion
      mobility cross sections of product ions in electron transfer dissociation.
      Finally, we demonstrate that the electron irradiation period influences the ratio
      of radical and even-electron c and z product ions. 

PMID- 26307727
TI  - Ion coalescence in Fourier transform mass spectrometry: should we worry about
      this in shotgun proteomics?
AB  - Coupling of motion of the ion clouds with close m/z values is a well-established
      phenomenon for ion- trapping mass analyzers. In Fourier transform ion cyclotron
      resonance mass spectrometry it is known as ion coalescence. Recently, ion
      coalescence was demonstrated and semiquantitatively characterized for the
      Orbitrap mass analyzer as well. When it occurs, the coalescence negatively
      affects the basic characteristics of a mass analyzer. Specifically, the dynamic
      range available for the high resolving power mass measurements reduces. In
      shotgun proteomics, another potentially adverse effect of ion coalescence is
      interference of the isotopic envelopes for the coeluting precursor ions of close
      m/z values, subjected to isolation before fragmentation. In this work we
      characterize coalescence events for synthetic peptide mixtures with fully and
      partially overlapping (13)C-isotope envelopes including pairs of peptides with
      glutamine deamidation. Furthermore, we demonstrate that fragmentation of the
      otherwise coalesced peptide ion clouds may remove the locking between them owing
      to the total charge redistribution between more ion species in the mass spectrum.
      Finally, we estimated the possible scale of the coalescence phenomenon for
      shotgun proteomics by considering the fraction of coeluted peptide pairs with the
      close masses using literature data for the yeast proteome. It was found that up
      to one tenth of all peptide identifications with the relative mass differences of
      20 ppm or less in the corresponding pairs may potentially experience the
      coalescence of the (13)C-isotopic envelopes. However, sample complexity in a real
      proteomics experiment and precursor ion signal splitting between many channels in
      tandem mass spectrometry drastically increase the threshold for coalescence, thus
      leading to practically coalescence-free proteomics based on Fourier transform
      mass spectrometry. 

PMID- 26307728
TI  - Effect of response factor variations on the response distribution of complex
      mixtures.
AB  - The goal of "comprehensive" or "untargeted" analysis is to generate a list of all
      the compounds of a particular type in a complex mixture. To this end, modern
      analytical techniques, including high-resolution mass spectrometry, enable the
      individual detection of hundreds to tens of thousands of compounds, which can
      have response magnitudes that span several orders of magnitude. Moreover, we and
      others have found that many comprehensive analyses of complex mixtures result in
      a log-normal distribution of measured responses. The response distribution is not
      the concentration distribution but is related to it through the distribution of
      component response factors (RFs). Here, we present a theoretical investigation of
      how the shape of the RF distribution can impact the distribution of measured
      responses. We show that several distributions of RFs combined with a log-normal
      distribution of concentrations result in log-normal distributions of responses.
      Additionally, we find that deviations from log-normal responses depend on the
      shape of the RF distribution, and that, when they occur, these deviations occur
      in the low-response regions of the response distribution, which would often be
      below the detection limits for real measurements. In all cases, applying a
      distribution of RFs to a concentration distribution results in a response
      distribution that is both broader than the original concentration distribution
      and has a lower mean value than it would if the RFs for all the components were
      unity. Further, the distorting effect of the RF distribution can impair the
      determination of the original concentration distribution and the prediction of
      the number and concentrations of the undetected components. 

PMID- 26307730
TI  - The dehydrogenation of alcohols and hydrocarbons by atomic metal anions.
AB  - The reactivity of anionic metal-carbonyl systems toward hydrocarbons, alcohols
      and a variety of other classes of molecules is well established in the
      literature. In this study we explored the reactions of atomic metal anions M(-),
      notably K(-), Cs(-), Co(-), Fe(-), Cu(-) and Ag(-), with alcohols, alkanes,
      alkenes and alkynes. All of the metal anions deprotonated the alcohols and
      alkynes. Also observed were the subsequent reactions of the resulting organic
      anions. Fe(-) and Cu(-) consistently displayed mono- and bis-dehydrogenation of
      primary and secondary alcohols, and alkanes, alkenes and alkynes to form MH(-)
      and MH(2)(-). Mechanisms for the dehydrogenation reactions are proposed and
      substantiated with isotopically-labelled reagents and thermochemical arguments.

PMID- 26307729
TI  - Simple mass spectrometric method for the estimation of boron and aluminum in
      water at the parts per billion level.
AB  - The coordinating nature of the hydroxy carboxylic acids, such as tartaric and
      citric acids, has been utilized for the in-situ formation of anions representing
      the trivalent elements boron and aluminum and two dianions of the hydroxy acid
      selected under negative electrospray ionization mass spectral conditions. The
      abundance of these ions could be used for the quantification of boron and
      aluminum in water at concentrations ranging from 4.0 ppb to 535.0 ppb. For a
      period of six months, the validity of this method was tested with citric acid as
      the coordinating agent. Thus, the developed method offers a simple means for the
      quantification of boron and aluminum in water by negative electrospray ionization
      mass spectrometry with a single quadrupole mass spectrometer.

PMID- 26307731
TI  - Hydrated copper ion chemistry: guided ion beam and computational investigation of
      Cu2+(H2O)n (n = 7-10) complexes.
AB  - Cross sections for the threshold collision-induced dissociation of
      Cu(2+)(H(2)O)(n), where n = 8 - 10, are measured using a guided ion beam tandem
      mass spectrometer. The primary dissociation pathway is found to be loss of a
      single water molecule followed by the sequential loss of additional water
      molecules until n = 8, at which point charge separation to form CuOH(+)(H(2)O)(4)
      (+) H(+)(H(2)O)(3) is observed to occur at a slightly lower energy than loss of a
      water molecule. Competition from charge separation prohibits the formation of
      appreciable amounts of the n = 7 or smaller complexes as reactants in the source.
      These findings indicate that Cu(2+) has a critical size of 8. Analysis of the
      data using statistical modeling techniques that account for energy distributions
      and lifetime effects yields primary and sequential bond dissociation energies
      (BDEs) for loss of one and two water molecules from n = 8 - 10 complexes as well
      as the barrier for charge separation from n = 8. More speculative analysis
      extends the thermochemistry obtained down to n = 5 and 6. Theoretical BDEs are
      determined from quantum chemical calculations using structures optimized at the
      B3LYP/6 311(+)G(d,p) level along with the lowest-energy isomers suggested by
      single point energies at the MP2(full), M06, B3LYP, and B3P86 levels of theory
      using a 6- 311(+)G(2d,2p) basis set. BDEs at 0K are converted to 298 K
      thermodynamic values using a rigid rotor/harmonic oscillator approximation.
      Experimental and theoretical entropies of activation suggest that a third solvent
      shell forms at n = 9, in accord with previous findings. The present work
      represents the first experimentally determined hydration enthalpies for the
      Cu(2+)(H(2)O)n system.

PMID- 26307732
TI  - Aluminum monocation basicity and affinity scales.
AB  - The experimental aspects of the determination of thermochemical data for the
      attachment of the aluminum monocation Al(+) to neutral atoms and molecules are
      reviewed. Literature aluminum cation affinities (enthalpy scale) and basicities
      (Gibbs energy scale) are tabulated and discussed. Ab initio quantum chemical
      calculations at the G4 level on 43 adducts provide a consistent picture of the
      energetics of the adducts and their structures. The Al(+)-ligand bonding is
      analyzed in terms of natural bond orbital and atom-in molecule analyses. A brief
      comparison of the Al(+) basicity scales and other gas- phase cation basicities is
      presented. 

PMID- 26307733
TI  - Reactions of stabilized aliphatic carbanions with esters of formic acid in the
      gas phase.
AB  - The reactions of nitromethane, acetonitrile, and ethyl acetate carbanions with
      formic acid esters were investigated in the gas phase by mass spectrometry and
      quantum chemical calculations. It was found that the carbanion of nitromethane
      practically does not react with formic acid esters and only traces of the Claisen
      type addition-elimination reaction product were observed. In the case of the
      deprotonated acetonitrile, the Claisen-type condensation that yielded the
      carbanion of cyanoacetaldehyde proceeded almost quantitatively for all the
      studied formates. Other products, like the Riveros reaction product, were
      observed in minor amounts. The ethyl acetate carbanion reacts with formates in a
      much more complex way because it decomposes in a collision cell, yielding the
      deprotonated ketene anion, which also can react with formic acid esters.
      Consequently, the Claisen condensation reaction products of both anions were
      observed as well as the products of other reactions. All the proposed reaction
      pathways were confirmed by quantum chemical calculations, including the
      transition-state energies. 

PMID- 26307734
TI  - Unimolecular dissociation of anions derived from maleic acid (MaH2) in the gas
      phase: MaH- and MaMgCl--- relationship to Grignard chemistry and reductive CO2
      fixation.
AB  - We have conducted collision induced dissociation experiments on the hydrogen
      maleate anion (MaH(-), m/z = 115) and the anionic maleate MgCl complex (MaMgC(-),
      m/z = 173). In addition, we have computationally investigated the observed
      fragmentation reactions. We find that both anions readily undergo two consecutive
      decarboxylations resulting in product ions at m/z = 71 and 27 for MaH(-), and at
      m/z = 129 and 85 for MaMgCl(-). The first decarboxylation is more facile for
      MaMgCl(-) than for MaH(-), while loss of CO(2) from Ma(-CO(2))H(-) is more facile
      than for Ma(-CO(2))MgCl(-). We also find that MaH(-) loses water, and we propose
      a mechanism for this loss. No first-generation fragmentation product other than
      Ma(-CO(2))MgCl(-) is seen for MaMgCl(-). Based on the observed unimolecular
      chemistry, we discuss some of its implications on reductive CO(2)-fixation and
      Grignard chemistry.

PMID- 26307735
TI  - Gas-phase reactions of the rhenium oxide anions, [ReOx]- (x = 2 - 4) with the
      neutral organic substrates methane, ethene, methanol and acetic acid.
AB  - The ion-molecule reactions of the rhenium oxide anions, [ReOx](-) (x = 2 - 4)
      with the organic substrates methane, ethene, methanol and acetic acid have been
      examined in a linear ion trap mass spectrometer. The only reactivity observed was
      between [ReO(2)](-) and acetic acid. Isotope labelled experiments and high
      resolution mass spectrometry measurements were used to assign the formulas of the
      ionic products. Collision-induced dissociation and ion-molecule reactions with
      acetic acid were used to probe the structures of the mass-selected primary
      product ions. Density functional theory calculations [PBE0/LanL2DZ6-311+G(d)]
      were used to suggest possible structures. The three primary product channels
      observed are likely to arise from the formation of: the metallalactone
      [ReO(2)(CH(2)CO(2))](-) (m/z 277) and H(2); [CH(3)ReO(2)(OH)](-) (m/z 251) and
      CO; and [ReO(3)](-) (m/z 235), H(2) and CH(2)CO.

PMID- 26307736
TI  - Gas-phase spectroscopy of a vinylheptafulvene chromophore.
AB  - The intrinsic spectral properties of the dihydroazulene (DHA)/vinylheptafulvene
      (VHF) photo/thermoswitch, free of solvent interactions, were investigated both
      experimentally and theoretically. A quaternary ammonium group was incorporated
      via an ethylene bridge to allow for the transfer of charged molecules to the gas
      phase by electrospray ionization, leaving the chromophore part itself neutral.
      Absorption by the two isomers was identified from ion dissociation (i.e., action
      spectroscopy) using a home-built sector instrument. Several fragment ions were
      observed, and dissociation occurred both at the charge tag side chain and at the
      chromophore unit itself. We measured an absorption band of VHF with a maximum at
      430 +/- 20 nm (2.9 eV +/- 0.1 eV) but no band was discernible for the DHA in the
      visible region. This shows that little interconversion between the two isomers
      occurs during the electrospray and the subsequent trapping in an octopole for 25
      ms; the latter is needed to produce ion bunches for spectroscopy where a pulsed
      laser system is used. For comparison, density functional theoretical calculations
      predicted lowest-energy vertical excitations of 3.33 eV to 3.48 eV for the DHA
      and 3.02 eV to 3.08 eV for the VHF (the ranges are based on the use of different
      functionals), which correspond to a maximal deviation between theory and
      experiment of 0.1 eV in the case of the VHF. The absorption by the bare ions is
      significantly blue-shifted compared to that by VHF in acetonitrile solution (2.64
      eV), but similar within the experimental uncertainty to that by VHF in
      cyclohexane (2.78 eV); the transition, therefore has a significant charge
      transfer character. Finally, we find that the absorption of two photons is needed
      to cause fragmentation of the VHF on the microsecond time scale, which indicates
      that prompt fragmentation from the electronically excited state or prior to the
      intramolecular vibrational redistribution of the excess energy plays no role.
      This is of particular importance for the use of the photosystem in advanced
      materials or molecular electronics where high photostability is required to allow
      for numerous isomerization cycles.

PMID- 26307737
TI  - Interaction of metal cations with alkylnitriles in the gas phase: solvation of
      metal ions by the hydrocarbon chain.
AB  - Relative affinity measurements of monovalent metal ions (M = Li(+), Na(+),
      Cu(+)and Ag(+)) toward aliphatic nitriles have been performed using the kinetic
      method by dissociation of metal bound dimer ions of the type R1C=N-M(+)-N=CR(2).
      It is found, particularly for Cu(+) and Ag(+), that the affinity towards nitriles
      having long chains (>C(6)) is markedly enhanced. This is attributed to a
      bidentate interaction of the metal ion with the nitrile moiety and the aliphatic
      chain. Theoretical calculations on the copper complexes show that these bidentate
      structures enjoy about 30% greater copper ion affinities compared to their linear
      counterparts. Such aliphatic interactions also play a major role in the
      dissociation chemistry of copper bound tetramers of the kind (RC=N)(4)Cu(2+?)
      where the long aliphatic chain R curls around the copper ion to facilitate
      electron transfer or a redox reaction to produce (RC=N)(2)Cu(+) + RC=N(+?) +
      RC=N.

PMID- 26307738
TI  - Gas-phase tyrosine-to-cysteine radical migration in model systems.
AB  - Radical migration, both intramolecular and intermolecular, from the tyrosine
      phenoxyl radical Tyr(O(?)) to the cysteine radical Cys(S(?)) in model peptide
      systems was observed in the gas phase. Ion-molecule reactions (IMRs) between the
      radical cation of homotyrosine and propyl thiol resulted in a fast hydrogen atom
      transfer. In addition, radical cations of the peptide LysTyrCys were formed via
      two different methods, affording regiospecific production of Tyr(O(?)) or
      Cys(S(?)) radicals. Collision-induced dissociation of these isomeric species
      displayed evidence of radical migration from the oxygen to sulfur, but not for
      the reverse process. This was supported by theoretical calculations, which showed
      the Cys(S(?)) radical slightly lower in energy than the Tyr(O(?)) isomer. IMRs of
      the LysTyrCys radical cation with allyl iodide further confirmed these findings.
      A mechanism for radical migration involving a proton shuttle by the C-terminal
      carboxylic group is proposed. 

PMID- 26307739
TI  - Photodissociation at various wavelengths: fragmentation studies of oxazine 170
      using nanosecond laser pulses.
AB  - The fragmentation of oxazine 170, a rhodamine-type dye, has been investigated by
      means of collisions and photodissociation with visible and ultraviolet radiation
      in a Fourier transform ion cyclotron resonance mass spectrometer. Because of an
      improved experimental setup, the photodissociation processes of stored ions are
      measured with high intensity with respect to the absorbed photons. By isotope
      labelling and quantum chemical calculations, the various fragmentation mechanisms
      are investigated. It is shown that the most important intermediate ion structure
      leading to the various ionic products is an even-electron azarine cation. Several
      new fragmentation mechanisms have been unveiled for the first time. 

PMID- 26307740
TI  - Fragmentation of protonated 2-(2-phenylethyl)chromones from agarwood: the
      diagnostic role of ion/neutral complexes as reactive intermediates.
AB  - A positive-ion electrospray ionisation collision-induced dissociation mass
      spectrometric study on the fragmentation of the [M + H](+) ions of 2-(2
      phenylethyl)chromone and a set of nine hydroxyl- and/or methoxy-substituted
      derivatives has revealed a highly prominent fragmentation channel, the loss of
      benzoquinomethanes or a benzaldehyde, respectively, as a diagnostic feature for 2
      (2-phenylethyl)chromones that bear a hydroxyl group at the para- (4'-), ortho-
      (2'-) and/or benzylic (alpha-) position of the phenylethyl residue. Derivatives
      that bear only a meta- (3'-) hydroxyl group do not undergo this elimination. The
      intermediacy of ion/neutral complexes (INCs) is invoked to explain this
      fragmentation, which involves the remarkable intra-complex proton or hydrogen
      atom transfer from the remote 4'-OH (or the 2'- or alpha-OH) functionalities.
      Density functional theory (B3LYP/6-31G(d)) calculations confirm the energetic
      preference for these elimination channels and agree with the limited
      thermochemical data known for para- and ortho- benzoquinomethanes. The INC
      mediated losses of the benzaldehydes from the [M + H](+) ions of the alpha
      hydroxy-substituted 2-(2-phenylethyl)chromones correspond to a particularly
      facile (vinylogous) Grob fragmentation. The study may be viewed as a telling
      example of the diagnostic role of ion/neutral complexes as intermediates for the
      structural assignment of constitutional isomers by mass spectrometry. 

PMID- 26307741
TI  - Individual steps of the Mizoroki-Heck reaction and intrinsic reactivity of
      intermediate organopalladium complexes studied in the gas phase.
AB  - The mechanism of the Mizoroki-Heck reaction (MHR) was analyzed by collision
      induced dissociation (CID) tandem-mass spectrometry and gas-phase ion/molecule
      reactions (IMRs) as well as by DFT computational analysis. The MHR was performed
      in the gas phase and the intrinsic reactivity of important intermediates was
      examined individually. Kinetics and substituent effects of cationic palladium-
      Pcy3-aryl complexes (Cy = cyclohexyl) with 2,3-dimethylbutadiene in the MHR were
      analyzed via IMRs and CID. The kinetics and ion structures of the species
      involved in the olefin insertion, i.e., the carbopalladation, were investigated.
      Moreover, linear free-energy correlations were applied and a concerted mechanism
      proceeding via a four-membered transition state for the carbopalladation step
      that exhibited only a minor charge separation was deduced. 

PMID- 26307742
TI  - Isomerization of metastable amine radical cations by dissociation-recombination.
AB  - The metastable molecular ions of primary aliphatic amines branched at C2 can
      isomerize by cleavage-recombination, thereby facilitating fragmentation reactions
      that require less energy than simple cleavage of the initial molecular ion. This
      process complements the reactions described by Audier to account for the
      conspicuous absence of the conventional a-cleavage among the major fragmentation
      reactions of the metastable molecular ions of primary amines. 

PMID- 26307743
TI  - On the role of a direct interaction between protein ions and solvent additives
      during protein supercharging by electrospray ionization mass spectrometry.
AB  - The addition of certain reagents during the electrospray ionization mass
      spectrometry of proteins can shift the protein ion signal charge-state
      distributions (CSDs) to higher average charge states, a phenomenon known as
      'supercharging'. The role of reagent gas-phase basicity (GB) during this process
      was investigated in both the negative and positive ion modes. Reagents with known
      or calculated GBs were added individually in equimolar amounts to protein
      solutions which were subsequently electrosprayed for mass spectrometry analysis.
      Shifts in the CSDs of the protein ion signals were monitored and related to the
      reagents' GBs. Trends for this data were evaluated for possible insights into a
      supercharging mechanism involving the direct interaction between supercharging
      reagent and protein ion. Reagent GB was confirmed to be directly related to the
      amount of supercharging observed in the negative ion mode. Supercharging in the
      positive ion mode, on the other hand, showed a maximal trend. Interestingly, a
      loss of signal and supercharging efficacy was observed for reagents with GBs
      intermediate within the investigated range, between ~800 and ~840 kJ mol(-1), at
      the 100 mM concentration used in the present study. The possibility of a direct
      interaction model for supercharging in the negative and positive ion modes
      dependent on the GBs of the protein ions and reagents is discussed. In the
      positive ion mode, supercharging appears to depend on the stability of a proton
      bridge formed between the reagent and a highly charged protein ion.

PMID- 26307745
TI  - In times, where the span of the life of man approaches 100 years. Introduction.

PMID- 26307746
TI  - Congratulations for Twenty Years of the European Journal of Mass Spectrometry.

PMID- 26307747
TI  - EJMS-the European Journal of Mass Spectrometry since 1994. Personal observations.

PMID- 26307748
TI  - Patterns of Infection and Patterns of Evolution: How a Malaria Parasite Brought
      "Monkeys and Man" Closer Together in the 1960s.
AB  - In 1960, American parasitologist Don Eyles was unexpectedly infected with a
      malariaparasite isolated from a macaque. He and his supervisor, G. Robert Coatney
      of the National Institutes of Health, had started this series of experiments with
      the assumption that humans were not susceptible to "monkey malaria." The
      revelation that a mosquito carrying a macaque parasite could infect a human
      raised a whole range of public health and biological questions. This paper
      follows Coatney's team of parasitologists and their subjects: from the human to
      the nonhuman; from the American laboratory to the forests of Malaysia; and
      between the domains of medical research and natural history. In the course of
      this research, Coatney and his colleagues inverted Koch's postulate, by which
      animal subjects are used to identify and understand human parasites. In contrast,
      Coatney's experimental protocol used human subjects to identify and understand
      monkey parasites. In so doing, the team repeatedly followed malaria parasites
      across the purported boundary separating monkeys and humans, a practical
      experience that created a sense of biological symmetry between these separate
      species. Ultimately, this led Coatney and his colleagues make evolutionary
      inferences, concluding "that monkeys and man are more closely related than some
      of us wish to admit." In following monkeys, men, and malaria across biological,
      geographical, and disciplinary boundaries, this paper offers a new historical
      narrative, demonstrating that the pursuit of public health agendas can fuel the
      expansion of evolutionary knowledge.

PMID- 26307749
TI  - An Uncommon Etiology for a Common Problem in an HIV-Positive Patient.

PMID- 26307750
TI  - Icariin Attenuates High-cholesterol Diet Induced Atherosclerosis in Rats by
      Inhibition of Inflammatory Response and p38 MAPK Signaling Pathway.
AB  - Icariin is a flavonoid isolated from the traditional Chinese herbal medicine
      Epimedium brevicornum Maxim and has been reported to be effective for the
      treatment of a variety of cardiovascular diseases. The aim of the present study
      was to investigate the effect and mechanism of icariin on atherosclerosis (AS)
      using a high-cholesterol diet (HCD)-induced rat model. Seventy male Wistar rats
      were divided into five groups: 20 in the control group, 20 in the AS group, 10 in
      the simvastatin group, 10 in the low-dose icariin group, and 10 in the high-dose
      icariin group. A HCD and vitamin D3 were administered to establish AS rat model.
      The five groups of rats received daily intragastric administration of normal
      saline, simvastatin, or icariin (30 mg/kg/d, 60 mg/kg/d) for 4 weeks. The levels
      of blood lipids, superoxide dismutase (SOD), and malonaldehyde (MDA) were
      measured. The mRNA levels of interleukin (IL)-6 and tumor necrosis factor (TNF)
      alpha were analyzed by real-time RT-PCR, and the serum levels of IL-6 and TNF
      alpha were measured using ELISA kit. In addition, the expression of
      phosphorylated p38 (p-p38) MAPK was detected by Western blot analysis. The
      results indicated that AS rat models were successfully constructed. In the AS
      group, the levels of blood lipids including total cholesterol (TC), triglyceride
      (TG), low-density lipoprotein-cholesterol (LDL-C), and MDA were significantly
      increased, while high-density lipoprotein-cholesterol (HDL-C) and SOD were
      significantly decreased, compared with those in the control group. However,
      icariin succeeded in improving these biochemical parameters towards the normal
      values in the control group. In the simvastatin group and the icariin groups, the
      serum levels of IL-6 and TNF-alpha and the related tissue mRNA levels, as well as
      the expression of p-p38 MAPK, were markedly reduced compared with the AS group.
      In conclusion, the present study indicated that icariin inhibited the HCD-induced
      dyslipidemia in rats, the mechanisms may be associated with the anti
      inflammation, anti-oxidative stress, and downregulation of p-p38 MAPK by icariin.

PMID- 26307751
TI  - Distribution of pseudoexfoliation material on anterior segment structures in
      human autopsy eyes after cataract surgery with intraocular lens implantation.
AB  - The purpose of the study was to evaluate the distribution and amount of
      pseudoexfoliation material (PXM) on anterior segment structures in pseudophakic
      human autopsy eyes with pseudoexfoliation (PEX) syndrome and to study its impact
      on fixation and decentration of posterior chamber intraocular lenses (IOLs).
      Sixteen human autopsy eyes (donor age [mean +/- SD] 77.5 +/- 8.6 years; range, 70
      90 years) with history of cataract surgery and PEX syndrome were analyzed for
      distribution and accumulation of PXM on structures of the anterior segment by
      light microscopy. Quantitative IOL decentration measurements were performed using
      the Miyake-Apple posterior view technique. All 16 eyes displayed IOLs which were
      either fixed symmetrically in the capsular bag (n = 8) or asymmetrically with one
      haptic in the sulcus and one in the bag (n = 7) or at the pars plicata of the
      ciliary body (n = 1). In the majority, PXM was found around the pars plicata
      (average grade: 1.6 +/- 0.53 um) and the lens capsule (average grade: 1.05 +/-
      0.46 um). Minor amounts were detected at the pars plana and the trabecular
      meshwork. IOL decentration measurements ranged from 0.51 +/- 0.35 (symmetrical
      fixation) to 0.61 +/- 0.43 mm (asymmetrical-fixation). There was only a weak
      statistically not significant correlation in regard to the amount of PXM and IOL
      decentration and between PXM distribution and the IOL fixation site. PXM
      contributes to weakening of the suspensory apparatus of the crystalline lens.
      Although PXM induced tissue alterations predispose for a broad spectrum of intra-
      and postoperative complications, the amount and distribution of PXM on different
      anterior segment structures showed only a weak correlation to IOL decentration or
      fixation location. 

PMID- 26307752
TI  - Association between downexpression of MiR-203 and poor prognosis in non-small
      cell lung cancer patients.
AB  - BACKGROUND AND AIM: Although miR-203 has been proposed as a relevant biomarker
      for several cancers, the validated prognostic significance of miR-203 in lung
      cancer remains obscure. Thus, we aimed to identify the relationship between miR
      203 expression and clinicopathological significance in non-small cell lung cancer
      (NSCLC) patients in the current study. METHODS: The expression of miR-203 in 125
      cases of NSCLC and their paired adjacent non-cancerous tissues was evaluated by
      quantitative reverse transcription polymerase chain reaction (qRT-PCR).
      Simultaneously, the correlation of miR-203 expression with a variety of
      clinicopathological factors and patient survival was analyzed. Functionally, in
      vitro effects of miR-203 on proliferation and viability were explored in lung
      cancer H460, A549, H1299, PC9 and H292 cells, as assessed by MTS tetrazolium
      assay and fluorimetric resorufin viability assay, respectively. RESULTS: The
      relative level of miR-203 was 6.12 +/- 6.25 in NSCLC tissues, remarkably
      downregulated than that of their paired non-tumorous lung tissues (7.88 +/- 5.56,
      P = 0.019). The area under curve (AUC) of low expression of miR-203 to diagnose
      NSCLC was 0.622 (95 % CI 0.552-0.692, P = 0.001). MiR-203 expression was
      negatively correlated to lymphatic metastasis (r = -0.334, P < 0.001), tumor size
      (r = -0.407, P < 0.001) and clinical TNM stages (r = -0.298, P = 0.001).
      Furthermore, the survival of the low miR-203 expression group was 4.88 +/- 4.38
      months, markedly shorter than that of the high expression group (23.35 +/- 1.12
      months, P < 0.001). The level of miR-203 was an independent prognostic indicator
      of NSCLC using univariate analysis. MiR-203 mimic could suppress the cell growth
      of five lung cancer cell lines tested to different degrees in vitro. CONCLUSIONS:
      MiR-203 could become a prognostic predictor in NSCLC and may be a new target for
      the molecular therapy of NSCLC patients.

PMID- 26307753
TI  - High pKDR immunohistochemical expression is an unfavourable prognostic biomarker
      in patients with advanced colorectal cancer treated with chemotherapy plus
      bevacizumab.
AB  - PURPOSE: To analyse the prognostic role of the immunohistochemical expression of
      pKDR in patients with advanced colorectal cancer treated with oxaliplatin and
      fluoropyrimidines combination chemotherapy with or without bevacizumab. METHODS:
      Retrospective multicentre study, carried out at four hospitals in the Valencian
      Community (Spain). Patients evolution was compared based on the
      immunohistochemical expression of pKDR, classified using 4 categories: 0
      (undetectable), 1 (mild), 2 (moderate) and 3 (high intensity). Patients were
      divided into two groups for the analysis: group 1 with low expression (0-1) vs.
      group 2 with high expression (2-3). RESULTS: Histological samples for the pKDR
      analysis were available for 84 of the 112 patients selected. Seven (8.3 %) had
      undetectable or mild expression of pKDR (Group 1) and 77 (91.7 %) showed moderate
      or high expression of pKDR (Group 2). Response rate in Group 1 was 100 % compared
      to 54.2 % in Group 2 (p = 0.019). Progression-free survival (PFS) (15 vs. 12
      months, p = 0.4) and overall survival (OS) (28 vs. 22 months, p = 0.09) were
      numerically but not significantly higher in patients from Group 1 vs. Group 2.
      Patients from Group 2 who received bevacizumab presented a significantly higher
      PFS (13 vs. 11, p = 0.015) and a numerically higher OS (23 vs. 17 months, p =
      0.27) than those treated exclusively with chemotherapy. CONCLUSIONS: Our results
      suggest that the absence or low expression of pKDR is associated with a better
      prognostic profile in patients with advanced colorectal cancer treated with
      chemotherapy and bevacizumab. Patients with a high pKDR expression benefit from
      the combination of chemotherapy with bevacizumab.

PMID- 26307755
TI  - Effect of Exclusive Breastfeeding on Rotavirus Infection among Children.
AB  - OBJECTIVES: To assess, whether exclusive breastfeeding plays a protective role in
      Rotavirus infection among children under age of five and to estimate whether
      breastfeeding has an impact on reducing the severity and symptoms among children
      infected with Rotavirus. METHODS: A systematic search was performed in Cochrane
      Central Register of Controlled Trials (CENTRAL), MEDLINE/PubMEd (from 1980 to
      present), ScienceDirect (from 1980 to present), OVID (from 1980 to present) and
      regional database IndMED. All the studies along with the research publications
      with descriptive, case series, cross sectional, case control and cohort studies
      (prospective and retrospective) that provided effectiveness of exclusive
      breastfeeding were considered for this review. Two review authors independently
      scrutinized the studies and extracted the data. In case of disagreement, the
      senior reviewer was consulted. RESULTS: Total seven studies qualified for the
      systematic review in which 6 studies qualified for meta-analysis. Exclusive
      breastfeeding was found to be effective in prevention of Rotavirus infection and
      in reducing the risk of Rotavirus infection among children (OR = 0.62, 95 % CI =
      0.48-0.81). CONCLUSIONS: This systematic review suggests that there is
      significant benefit in prevention of Rotavirus diarrhea among children by
      practicing exclusive breastfeeding throughout first 6 mo of life. Thereby, this
      study provides next reason to promote exclusive breastfeeding practice among
      mothers.

PMID- 26307754
TI  - Ionizing radiation exposure as a result of diagnostic imaging in patients with
      lymphoma.
AB  - PURPOSE: Survival rates among patients with lymphoma continue to improve.
      Strategies aimed at reducing potential treatment-related toxicity are
      increasingly prioritized. While radiological procedures play an important role,
      ionizing radiation exposure has been linked to an increased risk of malignancy,
      particularly among individuals whose cumulative radiation exposure exceeds a
      specific threshold (75 millisieverts). METHODS: Within this retrospective study,
      the cumulative radiation exposure dose was quantified for 486 consecutive
      patients with lymphoma. RESULTS: The median estimated total cumulative effective
      dose (CED) of ionizing radiation per subject was 69 mSv (42-118). However,
      younger patients (under 40 years) had a median CED of 89 mSv (55-124).
      CONCLUSION: This study highlights the considerable radiation exposure occurring
      among patients with lymphoma as a result of diagnostic imaging. To limit the risk
      of secondary carcinogenesis, consideration should be given to monitoring
      cumulative radiation exposure in individual patients as well as considering
      imaging modalities, which do not impart an ionizing radiation dose.

PMID- 26307756
TI  - Non Cystic Fibrosis Bronchiectasis.
AB  - Bronchiectasis is a pathological abnormality of the airways in which there is
      permanent dilatation and thickening of the airways. Precise incidence/prevalence
      in India is not known. Recent data suggests that about 1 % young children
      admitted in a hospital with pneumonia may develop bronchiectasis. Due to
      significant burden of pneumonia in young children in developing countries
      including India, it may be a significant problem that is possibly under
      recognized. Causes of bronchiectasis depend on the burden of respiratory
      infections and availability of the investigations for identification of the
      underlying cause. Post infectious causes are common in countries where infections
      are more common; however, since these countries are usually resource constrained
      and therefore, are not able to appropriately diagnose the other causes, leading
      to more than real overrepresentation of infections as a cause. In countries with
      less of infectious illnesses and good diagnostic facilities, malformations of
      airways, immune deficiency disorders and primary ciliary dyskinesia are common
      causes of bronchiectasis. High resolution CT scan of chest confirms the
      diagnosis. Treatment is supportive care and consists of maintenance of nutrition,
      airway clearance and antibiotics for exacerbations. Medical treatment is
      successful in the majority.

PMID- 26307757
TI  - Editorial: New Techniques for Old and New Diseases.

PMID- 26307758
TI  - Validation of prone myocardial perfusion SPECT with a variable-focus collimator
      versus supine myocardial perfusion SPECT with or without computed tomography
      derived attenuation correction.
AB  - OBJECTIVE: The purpose of this study is to evaluate whether prone myocardial
      perfusion single-photon emission computed tomography (MPS) with thallium-201
      acquired through a variable-focus collimator (IQ-SPECT) can correct for soft
      tissue attenuation. METHODS: Thirty-nine patients underwent thallium-201 stress
      MPS with IQ-SPECT. Delayed images acquired with the patients in the prone
      position were compared with delayed images obtained with the patients in the
      supine position with computed tomography-derived attenuation correction (CTAC) (S
      CTAC images) or without CTAC (S-NCTAC images). Quantitative tracer uptake (QTU)
      and semi-quantitative defect scores were determined for the 17 standard
      myocardial segments. Segments were categorized into anterior-anteroseptal,
      lateral, inferior, and apex, and areas with defect decision were determined by
      using the defect scores. RESULTS: Image quality in the prone images was similar
      to that of S-NCTAC and S-CTAC images. In male patients, QTU in prone images was
      equivalent to that in S-CTAC images in the anterior-anteroseptal area, but was
      significantly lower than that in S-CTAC images in the inferior area. In female
      patients, QTU in prone images was similar to that in S-CTAC images in the
      anterior-anteroseptal, lateral, and inferior areas. In male and in female
      patients, QTU in the apex was significantly greater in the prone images than that
      in the S-CTAC images. In the combined male and female patient group, the defect
      decision for prone images was similar to that for S-CTAC images in the anterior
      anteroseptal, lateral, and inferior areas. Apical defects were observed more
      frequently in S-CTAC images than in prone or S-NCTAC images. CONCLUSIONS: Fewer
      artificial defects were observed in the apex of images acquired by prone imaging
      than by S-CTAC imaging. Prone images improved attenuation and had similar defect
      decision as S-CTAC images in the anterior-anteroseptal, lateral, and inferior
      areas.

PMID- 26307760
TI  - Cheat invasion causes bacterial trait loss in lung infections.

PMID- 26307759
TI  - Challenges and Strategies in Thermal Processing of Amorphous Solid Dispersions: A
      Review.
AB  - Thermal processing of amorphous solid dispersions continues to gain interest in
      the pharmaceutical industry, as evident by several recently approved commercial
      products. Still, a number of pharmaceutical polymer carriers exhibit thermal or
      viscoelastic limitations in thermal processing, especially at smaller scales.
      Additionally, active pharmaceutical ingredients with high melting points and/or
      that are thermally labile present their own specific challenges. This review will
      outline a number of formulation and process-driven strategies to enable thermal
      processing of challenging compositions. These include the use of traditional
      plasticizers and surfactants, temporary plasticizers utilizing sub- or
      supercritical carbon dioxide, designer polymers tailored for hot-melt extrusion
      processing, and KinetiSol(r) Dispersing technology. Recent case studies of each
      strategy will be described along with potential benefits and limitations. 

PMID- 26307762
TI  - Diverse set of Turing nanopatterns coat corneae across insect lineages.
AB  - Nipple-like nanostructures covering the corneal surfaces of moths, butterflies,
      and Drosophila have been studied by electron and atomic force microscopy, and
      their antireflective properties have been described. In contrast, corneal
      nanostructures of the majority of other insect orders have either been unexamined
      or examined by methods that did not allow precise morphological characterization.
      Here we provide a comprehensive analysis of corneal surfaces in 23 insect orders,
      revealing a rich diversity of insect corneal nanocoatings. These nanocoatings are
      categorized into four major morphological patterns and various transitions
      between them, many, to our knowledge, never described before. Remarkably, this
      unexpectedly diverse range of the corneal nanostructures replicates the complete
      set of Turing patterns, thus likely being a result of processes similar to those
      modeled by Alan Turing in his famous reaction-diffusion system. These findings
      reveal a beautiful diversity of insect corneal nanostructures and shed light on
      their molecular origin and evolutionary diversification. They may also be the
      first-ever biological example of Turing nanopatterns. 

PMID- 26307763
TI  - Fmr1 deficiency promotes age-dependent alterations in the cortical synaptic
      proteome.
AB  - Fragile X syndrome (FXS) is an X-linked neurodevelopmental disorder characterized
      by severe intellectual disability and other symptoms including autism. Although
      caused by the silencing of a single gene, Fmr1 (fragile X mental retardation 1),
      the complexity of FXS pathogenesis is amplified because the encoded protein,
      FMRP, regulates the activity-dependent translation of numerous mRNAs. Although
      the mRNAs that associate with FMRP have been extensively studied, little is known
      regarding the proteins whose expression levels are altered, directly or
      indirectly, by loss of FMRP during brain development. Here we systematically
      measured protein expression in neocortical synaptic fractions from Fmr1 knockout
      (KO) and wild-type (WT) mice at both adolescent and adult stages. Although
      hundreds of proteins are up-regulated in the absence of FMRP in young mice, this
      up-regulation is largely diminished in adulthood. Up-regulated proteins included
      previously unidentified as well as known targets involved in synapse formation
      and function and brain development and others linked to intellectual disability
      and autism. Comparison with putative FMRP target mRNAs and autism susceptibility
      genes revealed substantial overlap, consistent with the idea that the autism
      endophenotype of FXS is due to a "multiple hit" effect of FMRP loss, particularly
      within the PSD95 interactome. Through studies of de novo protein synthesis in
      primary cortical neurons from KO and WT mice, we found that neurons lacking FMRP
      produce nascent proteins at higher rates, many of which are synaptic proteins and
      encoded by FMRP target mRNAs. Our results provide a greatly expanded view of
      protein changes in FXS and identify age-dependent effects of FMRP in shaping the
      neuronal proteome. 

PMID- 26307766
TI  - Screening for cancer of the prostate: Do we have a state of the art?

PMID- 26307765
TI  - Small RNA-based feedforward loop with AND-gate logic regulates extrachromosomal
      DNA transfer in Salmonella.
AB  - Horizontal gene transfer via plasmid conjugation is a major driving force in
      microbial evolution but constitutes a complex process that requires
      synchronization with the physiological state of the host bacteria. Although
      several host transcription factors are known to regulate plasmid-borne transfer
      genes, RNA-based regulatory circuits for host-plasmid communication remain
      unknown. We describe a posttranscriptional mechanism whereby the Hfq-dependent
      small RNA, RprA, inhibits transfer of pSLT, the virulence plasmid of Salmonella
      enterica. RprA employs two separate seed-pairing domains to activate the mRNAs of
      both the sigma-factor sigma(S) and the RicI protein, a previously uncharacterized
      membrane protein here shown to inhibit conjugation. Transcription of ricI
      requires sigma(S) and, together, RprA and sigma(S) orchestrate a coherent
      feedforward loop with AND-gate logic to tightly control the activation of RicI
      synthesis. RicI interacts with the conjugation apparatus protein TraV and limits
      plasmid transfer under membrane-damaging conditions. To our knowledge, this study
      reports the first small RNA-controlled feedforward loop relying on
      posttranscriptional activation of two independent targets and an unexpected role
      of the conserved RprA small RNA in controlling extrachromosomal DNA transfer. 

PMID- 26307767
TI  - Effectiveness of bronchial thermoplasty in severe asthma in 'real life' patients
      compared with those recruited to clinical trials in the same centre.
AB  - Published information on the effectiveness of bronchial thermoplasty (BT) for
      severe asthma in 'real life' patients is limited. We compared safety and efficacy
      outcomes 12 months post procedure in 10 clinic patients and 15 patients recruited
      to clinical trials of BT at the same centre. Baseline asthma severity was greater
      in the clinic group. Adverse events were similar. Clinical improvements occurred
      in 50% of the clinic patients compared with 73% of the research patients.

PMID- 26307768
TI  - miRNA Multiplayers in glioma. From bench to bedside.
AB  - Glioblastoma multiforme (GBM) is the most common type of malignant gliomas,
      characterized by genetic instability, intratumoral histopathological variability
      and unpredictable clinical behavior. Disappointing results in the treatment of
      gliomas with surgery, radiation and chemotherapy have fuelled a search for a new
      therapeutic targets and treatment modalities. A novel small non-coding RNA
      molecules, microRNAs (miRNAs), appear to represent one of the most attractive
      target molecules contributing to the pathogenesis of various types of tumors.
      They play crucial roles in tumorigenesis, angiogenesis, invasion and apoptosis.
      Some miRNAs are also associated with clinical outcome and chemo- and radiotherapy
      resistance. Moreover, miRNA have the potential to affect the responses to
      molecular-targeted therapies and they also might be associated with cancer stem
      cell properties, affecting tumor maintenance and progression. The expression
      profiles of miRNAs are also useful for subclassification of GBM, what underscores
      the heterogeneity of diseases that all share the same WHO histopathological
      grade. Importantly, molecular subtypes of GBM appear to correlate with clinical
      phenotypes, tumor characteristic and treatment outcomes. miRNAs are then
      biological markers with possible diagnostic and prognostic potential. They could
      also serve as one of the promising treatment targets in human glioblastoma. 

PMID- 26307764
TI  - Epigenetic mechanisms, T-cell activation, and CCR5 genetics interact to regulate
      T-cell expression of CCR5, the major HIV-1 coreceptor.
AB  - T-cell expression levels of CC chemokine receptor 5 (CCR5) are a critical
      determinant of HIV/AIDS susceptibility, and manifest wide variations (i) between
      T-cell subsets and among individuals and (ii) in T-cell activation-induced
      increases in expression levels. We demonstrate that a unifying mechanism for this
      variation is differences in constitutive and T-cell activation-induced DNA
      methylation status of CCR5 cis-regulatory regions (cis-regions). Commencing at an
      evolutionarily conserved CpG (CpG -41), CCR5 cis-regions manifest lower vs.
      higher methylation in T cells with higher vs. lower CCR5 levels (memory vs. naive
      T cells) and in memory T cells with higher vs. lower CCR5 levels. HIV-related and
      in vitro induced T-cell activation is associated with demethylation of these cis
      regions. CCR5 haplotypes associated with increased vs. decreased gene/surface
      expression levels and HIV/AIDS susceptibility magnify vs. dampen T-cell
      activation-associated demethylation. Methylation status of CCR5 intron 2 explains
      a larger proportion of the variation in CCR5 levels than genotype or T-cell
      activation. The ancestral, protective CCR5-HHA haplotype bears a polymorphism at
      CpG -41 that is (i) specific to southern Africa, (ii) abrogates binding of the
      transcription factor CREB1 to this cis-region, and (iii) exhibits a trend for
      overrepresentation in persons with reduced susceptibility to HIV and disease
      progression. Genotypes lacking the CCR5-Delta32 mutation but with hypermethylated
      cis-regions have CCR5 levels similar to genotypes heterozygous for CCR5-Delta32.
      In HIV-infected individuals, CCR5 cis-regions remain demethylated, despite
      restoration of CD4+ counts (>=800 cells per mm(3)) with antiretroviral therapy.
      Thus, methylation content of CCR5 cis-regions is a central epigenetic determinant
      of T-cell CCR5 levels, and possibly HIV-related outcomes. 

PMID- 26307769
TI  - Proteomics in studies of Staphylococcus aureus virulence.
AB  - Staphylococcus aureus is a widespread, opportunistic pathogen that causes
      community and hospital acquired infections. Its high pathogenicity is driven by
      multifactorial and complex mechanisms determined by the ability of the bacterium
      to express a wide variety of virulence factors. The proteome secreted into
      extracellular milieu is a rich reservoir of such factors which include mainly
      nonenzymatic toxins and enzymes. Simultaneously, membrane proteins, membrane-cell
      wall interface proteins and cell wall-associated proteins also strongly influence
      staphylococcal virulence. Proteomics shows a great potential in exploring the
      role of the extracellular proteome in cell physiology, including the pathogenic
      potential of particular strains of staphylococci. In turn, understanding the
      bacterial physiology including the interconnections of particular factors within
      the extracellular proteomes is a key to the development of the ever needed, novel
      antibacterial strategies. Here, we briefly overview the latest applications of
      gel-based and gel-free proteomic techniques in the identification of the
      virulence factors within S. aureus secretome and surfacome. Such studies are of
      utmost importance in understanding the host-pathogen interactions, analysis of
      the role of staphylococcal regulatory systems and also the detection of
      posttranslational modifications emerging as important modifiers of the infection
      process. 

PMID- 26307770
TI  - Multidirectional effects of triterpene saponins on cancer cells - mini-review of
      in vitro studies.
AB  - Triterpene saponins (saponosides) are found in a variety of higher plants and
      display a wide range of pharmacological activities, including expectorant, anti
      inflamatory, vasoprotective, gastroprotective and antimicrobial properties.
      Recently, a potential anticancer activity of saponins has been suggested by their
      cytotoxic, cytostatic, pro-apoptotic and anti-invasive effects. At high
      concentrations (more than 100 uM) saponins exert cytotoxic and haemolytic effects
      via permeabilization of the cell membranes. Noteworthy, the inhibition of cancer
      cell proliferation, the induction of apoptosis and attenuation of cell
      invasiveness is observed in the presence of low saponin concentrations. Saponins
      might affect the expression of genes associated with malignancy. These
      alterations are directly related to the invasive phenotype of cancer cells and
      depend on "cellular context". It illustrates the relationships between the action
      of saponins, and the momentary genomic/proteomic status of cancer cells. Here, we
      discuss the hallmarks of anti-cancer activity of saponins with the particular
      emphasis on anti-invasive effect of diverse groups of saponins that have been
      investigated in relation to tumor therapy. 

PMID- 26307771
TI  - Antibacterial activity of caffeine against plant pathogenic bacteria.
AB  - The objective of the present study was to evaluate the antibacterial properties
      of a plant secondary metabolite - caffeine. Caffeine is present in over 100 plant
      species. Antibacterial activity of caffeine was examined against the following
      plant-pathogenic bacteria: Ralstonia solanacearum (Rsol), Clavibacter
      michiganesis subsp. sepedonicus (Cms), Dickeya solani (Dsol), Pectobacterium
      atrosepticum (Pba), Pectobacterium carotovorum subsp. carotovorum (Pcc),
      Pseudomonas syringae pv. tomato (Pst), and Xanthomonas campestris subsp.
      campestris (Xcc). MIC and MBC values ranged from 5 to 20 mM and from 43 to 100
      mM, respectively. Caffeine increased the bacterial generation time of all tested
      species and caused changes in cell morphology. The influence of caffeine on the
      synthesis of DNA, RNA and proteins was investigated in cultures of plant
      pathogenic bacteria with labelled precursors: [(3)H]thymidine, [(3)H]uridine or
      (14)C leucine, respectively. RNA biosynthesis was more affected than DNA or
      protein biosynthesis in bacterial cells treated with caffeine. Treatment of Pba
      with caffeine for 336 h did not induce resistance to this compound. Caffeine
      application reduced disease symptoms caused by Dsol on chicory leaves, potato
      slices, and whole potato tubers. The data presented indicate caffeine as a
      potential tool for the control of diseases caused by plant-pathogenic bacteria,
      especially under storage conditions. 

PMID- 26307775
TI  - Nuclease activity and interaction studies of unsymmetrical binuclear Ni(II)
      complexes with CT-DNA and BSA.
AB  - New unsymmetrical binuclear nickel(II) complexes [Ni2L(1-5)] (ClO4)2 (1-5) were
      synthesized by using [NiL] [(3-((9E)-(2-((E)-(3-formyl-2-olato-5
      methylbenzylideneamino)methyl) phenylimino)methyl)-3-formyl-5-methyl-2
      olato)nickel(II)] with various diamines like 1,2-diaminoethane (L(1)), 1,3
      diaminopropane (L(2)), 1,4-diaminobutane (L(3)), 1,2-diaminobenzene (L(4)) and
      1,8-diaminonaphthalene (L(5)) and characterized by elemental analysis and
      spectroscopic methods. The molecular structure of binuclear nickel(II) complex 1
      is determined by a single crystal X-ray diffraction method. Cyclic voltammograms
      of binuclear Ni(II) complexes exhibit two quasi-reversible reduction waves in the
      cathodic region and two oxidation waves in the anodic region. DNA binding,
      protein binding and DNA cleavage studies were investigated. The interactions of
      complexes (1-5) with calf thymus DNA were studied by spectroscopic techniques,
      including absorption and fluorescence methods. The binding affinities of
      complexes (1-5) with CT-DNA and nuclease activities are in the following order:
      5> 4>3 >2>1 . Binuclear Ni(II) complex 1 cleaved the plasmid DNA by a hydrolytic
      pathway. The hydrolytic cleavage of DNA by the complexes is supported by evidence
      from free radical quenching and T4 ligase ligation. Binuclear Ni(II) complexes (1
      5) displayed significant protein (bovine serum albumin) interactions. The
      experimental results showed that the interaction between binuclear Ni(II)
      complexes and BSA was mainly a static quenching process.

PMID- 26307776
TI  - Reflections ... they called it 'restructuring'.

PMID- 26307777
TI  - Rationing healthcare in South Africa:   Renal replacement therapy - a case in  
      point.

PMID- 26307778
TI  - Improved surgical output in   district hospitals relies more on   softer
      ingredients than on formal   postgraduate training time.

PMID- 26307779
TI  - Access to flucytosine for HIV-infected   patients with cryptococcal meningitis   
      an urgent need.

PMID- 26307780
TI  - Shielding blood donors from   harm.

PMID- 26307781
TI  - CoN - lifeline for patients, noose for   healthcare providers?

PMID- 26307782
TI  - Promote cheaper generic drugs to patients - and help contain medical inflation.

PMID- 26307783
TI  - Breaching the chasm between what's law and what's done.

PMID- 26307784
TI  - Women's health and human rights.

PMID- 26307786
TI  - Papshop: Not a 'melon'choly Pap smear workshop!

PMID- 26307785
TI  - Obstetric medicine: Interlinking   obstetrics and internal medicine.
AB  - Medical problems account for almost 50% of all maternal deaths in South Africa.
      The most recent report of the National Committee on Confidential Enquiries into
      Maternal Deaths (NCCEMD) (2008 - 2010) stated that 40.5% of deaths were due to
      non-pregnancy-related infections, which are mostly HIV-related, and 8.8% were due
      to medical or surgical disorders. Obstetric physicians have a specific role in
      managing pregnant and postpartum women with medical problems and, in partnership
      with obstetricians, can contribute to reducing maternal morbidity and mortality.
      There are physiological changes in almost all systems in pregnancy. For example,
      changes in the cardiovascular, respiratory and haematological systems are
      particularly important when assessing the cause and management of medical
      problems in pregnant women. Such problems may be unique to pregnancy, exacerbated
      by pregnancy, or unrelated to pregnancy. They may be present prior to pregnancy,
      or present for the first time in pregnancy. Some medical problems are worsened by
      pregnancy. Pregnant women may improve or remain stable, or their disease may
      predictably or unpredictably deteriorate. This article discusses the role of
      obstetric physicians in managing medical problems in pregnant women. A case is
      described of a pregnant woman with common medical problems, resulting in a
      serious complication when treatment is interrupted.

PMID- 26307788
TI  - Pregnancy and the kidneys.

PMID- 26307787
TI  - Pregnancy and cardiac disease.

PMID- 26307790
TI  - Contraception: Everyone's responsibility.

PMID- 26307789
TI  - Rheumatic diseases and pregnancy.

PMID- 26307791
TI  - Mission unstoppable? - the full empowerment of women.

PMID- 26307792
TI  - Time to stop preventable deaths from unsterile traditional male circumcision
      practices.

PMID- 26307793
TI  - Mammography reporting at Tygerberg Hospital, Cape Town, South Africa.

PMID- 26307794
TI  - HPV vaccine: Why the rush?

PMID- 26307795
TI  - HPV vaccine: Can we afford to hesitate?

PMID- 26307796
TI  - GeneXpert TB 8: A point-of-care diagnostic pilot.

PMID- 26307797
TI  - Professional competence in South Africa.

PMID- 26307798
TI  - Professional competence in South Africa.

PMID- 26307799
TI  - TB: the tap's down a notch - but the water's polluted.

PMID- 26307800
TI  - Defusing the new drug-resistant TB time bomb.

PMID- 26307801
TI  - Timing their moves, healthcare bodies scrub up for a dust-up.

PMID- 26307802
TI  - Patient lost in the private healthcare mix - Broomberg.

PMID- 26307803
TI  - Climate change: One of the greatest threats to public health in the 21st century.

PMID- 26307804
TI  - Human health impacts in a changing South African climate.
AB  - Climate change is projected to lead to warmer temperatures, especially in
      southern Africa, where the warming is predicted to be 2 degrees C higher than the
      global increase. Given the high burden of disease already associated with
      environmental factors in this region, this temperature increase may lead to grave
      challenges for human health and quality of life. HIV/AIDS, poverty, food and
      water insecurity together with inequality and unemployment will further
      complicate the manner in which we will need to address the challenges of a
      changing climate. The health impacts are direct, such as increased temperatures
      leading to heat exhaustion, and indirect, such as likely increases in infectious
      diseases from contaminated water and changes in the distribution and/or magnitude
      of vector-borne diseases. The most effective measures for adapting to climate
      change to ensure healthy populations are to implement basic public health systems
      and services. These range from a continuous supply of clean water to adequate
      primary healthcare services. Support for required interventions is required not
      only from government, but also from healthcare professionals and communities. The
      need for disease surveillance, data capturing and more focused research is
      paramount.

PMID- 26307805
TI  - The HIV/AIDS epidemic in South Africa: Convergence with tuberculosis,
      socioecological vulnerability, and climate change patterns.

PMID- 26307806
TI  - National policy response to climate change in South Africa.

PMID- 26307807
TI  - Socially, politically and economically mediated health effects of climate change:
      Possible consequences for Africa.

PMID- 26307808
TI  - Climate change and occupational health: A South African perspective.

PMID- 26307809
TI  - A systematic review of computed tomography detection of cartilage invasion in
      laryngeal carcinoma.
AB  - OBJECTIVES/HYPOTHESIS: This systematic review aimed to assess the diagnostic
      value of computed tomography (CT) in detecting cartilage invasion among patients
      with laryngeal carcinoma. DATA SOURCES: PubMed, Embase, and the Cochrane Library.
      REVIEW METHODS: A search in the previously mentioned databases was performed to
      identify relevant articles. Articles comparing cartilage invasion on CT with
      histology were selected. After critical appraisal, articles of adequate relevance
      and validity were included in further analysis. Prevalences, sensitivity,
      specificity, positive predictive values, and negative predictive values were
      extracted from the included articles. RESULTS: Four studies were included in the
      final analysis. Only one study examined the positive predictive value and
      negative predictive value for invasion of any laryngeal cartilage, and they were
      87% and 56%, respectively. The positive predictive value and negative predictive
      value for thyroid cartilage invasion were investigated in three studies and
      ranged from 44% to 80% and from 85% to 100%, respectively. The negative
      predictive value is likely underestimated due to selection bias, whereas the
      positive predictive value is likely overestimated. CONCLUSIONS: CT imaging is a
      suitable tool to assess laryngeal cartilage invasion, especially regarding the
      thyroid cartilage.

PMID- 26307812
TI  - Preface.

PMID- 26307813
TI  - Preface.

PMID- 26307814
TI  - Pyrosequencing Technology. Preface.

PMID- 26307816
TI  - Preface.

PMID- 26307815
TI  - Preface.

PMID- 26307817
TI  - Response.

PMID- 26307818
TI  - Response.

PMID- 26307819
TI  - Response.

PMID- 26307820
TI  - Response.

PMID- 26307821
TI  - Trilateral '3P' Mechanics of Stabilized Layersomes Technology for Efficient Oral
      Immunization.
AB  - The main objective of the present work is to investigate the potential of
      polyelectrolyte stabilized layersomes as vaccine adjuvants for oral immunization.
      Herein, bovine serum albumin (BSA) loaded vesicular nanoformulations were
      prepared via thin film hydration method. The effect of various explanatory
      variables on responses were examined by a 6-factor, 3-level Box-Behnken design
      using JMP statistical software. An improved stability of vesicular
      nanoformulations in simulated biological media revealed that alternate layer-by
      layer coating using polyacrylic acid and polyallylamine hydrochloride improved
      the robustness of vesicular structure. The formulation was lyophilized to improve
      long-term storage stability using trehalose as cryoprotectant. As evident from in
      process stability analysis, the chemicals, process and lyophilization conditions
      had no detrimental effect on the conformational stability and integrity of
      antigen. Mathematical modelling and DDsolver analysis confirmed that the release
      profile of vesicular nanoformulations altered from Baker-Lonsdale to Higuchi
      fashion, following integration of layer-by-layer coating. Confocal microscopy and
      spectrofluorometric quantification demonstrated a selective, dose and time
      dependent accumulation of nanoformulations in antigen presenting cells. As
      evident from in vivo immunization study, layersomes produced higher humoral (mean
      IgG in serum), mucosal (mean sIgA titre in biological fluids) and cellular immune
      response (IL-2 and IFN-y level) compared to free antigen. The observed effects
      might be attributed to improved protection, permeation and presentation of
      antigen using layersomes. In conclusion, polyelectrolyte stabilized vesicular
      nanoformulations contribute promising toolbox for mass immunization using
      human/veterinary vaccine or other protein/peptides delivery especially by oral
      route.

PMID- 26307822
TI  - Arginine-Glycine-Aspartic Acid-Modified Lipid-Polymer Hybrid Nanoparticles for
      Docetaxel Delivery in Glioblastoma Multiforme.
AB  - Hybrid nanoparticles consisting of lipids and the biodegradable polymer, poly
      (D,L-lactide-co-glycolide) (PLGA), were developed for the targeted delivery of
      the anticancer drug, docetaxel. Transmission electron microscopic observations
      confirmed the presence of a lipid coating over the polymeric core. Using coumarin
      6 as a fluorescent probe, the uptake efficacy of RGD conjugated lipid coated
      nanoparticles (RGD-L-P) by C6 cells was increased significantly, compared with
      that of lipid-polymer hybrid nanoparticles (L-P; 2.5-fold higher) or PLGA
      nanoparticles (PLGA-P; 1.76-fold higher). The superior tumor spheroid penetration
      of RGD-L-P indicated that RGD-L-P could target effectively and specifically to C6
      cells overexpressing integrin alpha(v)beta3. The anti-proliferative activity of
      docetaxel-loaded RGD-L-P against C6 cells was increased 2.69- and 4.13-fold
      compared with L-P and PLGA-P, respectively. Regarding biodistribution, the
      strongest brain-localized fluorescence signals were detected in glioblastoma
      multiforme (GBM)-bearing rats treated with 1,10-Dioctadecyl-3,3,30,30
      tetramethylindotricarb-ocyanine iodide (DiR)-loaded RGD-L-P, compared to rats
      treated with DiR-loaded L-P or PLGA-P. The median survival time of GBM-bearing
      rats treated with docetaxel-loaded RGD-L-P was 57 days, a fold increase of 1.43,
      1.78, 3.35, and 3.56 compared with animals given L-P (P < 0.05), PLGA-P (P <
      0.05), Taxotere (P < 0.01) and saline (P < 0.01), respectively. Collectively,
      these results support RGD-L-P as a promising drug delivery system for the
      specific targeting and the treatment of GBM.

PMID- 26307823
TI  - Multi Drug Loaded Thermo-Responsive Fibrinogen-graft-Poly(N-vinyl Caprolactam)
      Nanogels for Breast Cancer Drug Delivery.
AB  - This study aims at the targeted delivery of 5-fluorouracil (5-FU) and Megestrol
      acetate (Meg) loaded fibrinogen-graft-poly(N-Vinyl caprolactam) nanogels (5
      FU/Meg-fib-graft-PNVCL NGs) toward alpha5beta1-integrins receptors expressed on
      breast cancer cells to have enhanced anti-cancer effect in vitro. To achieve this
      aim, we developed biocompatible thermoresponsive fib-graft-PNVCL NGs using
      fibrinogen and carboxyl terminated PNVCL via EDC/NHS amidation reaction. The
      Lower Critical Solution Temperature (LCST) of fib-graft-PNVCL could be tuned
      according to PNVCL/fibrinogen compositions. The 100-120 nm sized nanogels of fib
      graft-PNVCL (LCST = 35 ?1 'C) was prepared using CaCl2 cross-linker. The 5-FU/Meg
      fib-graft-PNVCL NGs showed a particle size of 150-170 nm size. The drug loading
      efficiency with 5-FU was 62% while Meg showed 74%. The 5-FU and Meg release was
      prominent above LCST than below LCST. The multi drug loaded fib-graft-PNVCL NGs
      showed enhanced toxicity, apoptosis and uptake by breast cancer (MCF-7) cells
      compared to their individual doses above their LCST. The in vivo assessment in
      Swiss albino mice showed sustained release of Meg and 5-FU as early as 3 days,
      confirming the therapeutic efficiency of the formulation. These results
      demonstrate an enhanced platform for the future animal studies on breast tumor
      xenograft model.

PMID- 26307824
TI  - Intracellular Uptake of Curcumin-Loaded Solid Lipid Nanoparticles Exhibit Anti
      Inflammatory Activities Superior to Those of Curcumin Through the NF-kappaB
      Signaling Pathway.
AB  - Curcumin (Cur) is a naturally derived, novel anti-inflammatory agent, but its
      poor solubility limits its clinical use. The aim of the present study was to
      encapsulate Cur into solid lipid nanoparticles (SLNs) to improve its anti
      inflammatory activity. The Cur-loaded SLNs (Cur-SLNs) were prepared using
      emulsification and low-temperature solidification methods. In contrast to free
      Cur, the particles were well dispersed in aqueous medium, showing a narrow size
      distribution with a range of 55 : 1.2 nm, a zeta potential value of -26.2 +/- 1.3
      mV, and a high drug loading efficiency of 37% +/- 2.5%. The sustained release of
      Cur was observed for up to 6 days. The particles displayed enhanced stability in
      phosphate-buffered saline by protecting the encapsulated Cur against hydrolysis
      and biotransformation, as well as increasing biocompatibility. Cur-SLNs were more
      effective than free Cur at reducing the expression levels of several pro-
      inflammatory mediators, including inflammatory cytokines (IL-6, TNF-alpha, and IL
      1beta) and nitric oxide (NO), under in vitro conditions. By Western blotting, we
      found that Cur-SLNs were more active than free Cur in inhibiting the LPS-induced
      activation of the inflammatory transcription factor NF-kappaB through the
      suppression of IkappaB kinase activation. Compared to free Cur, Cur-SLNs had an
      increased intracellular uptake over time (observed after 24 h) in RAW264.7 cells.
      Moreover, the Cur-SLNs (>= 20 MUM) significantly improved RAW264.7 cell viability
      by inhibiting apoptosis. Thus, these results demonstrated that SLNs could be used
      as potential anti-inflammatory drug carriers for the treatment of various chronic
      diseases.

PMID- 26307825
TI  - Thermosensitive Gel Containing Cellulose Acetate Phthalate-Efavirenz Combination
      Nanoparticles for Prevention of HIV-1 Infection.
AB  - The objective of this investigation was to develop and evaluate a nano
      microbicide containing a combination of cellulose acetate phthalate (HIV-1 entry
      inhibitor) and efavirenz (anti-HIV agent) for HIV prophylaxis. Cellulose acetate
      phthalate-efavirenz combination nanoparticles (CAP-EFV-NPs) were fabricated by
      the nanoprecipitation method and were characterized for particle size, zeta
      potential and encapsulation efficiency of efavirenz. CAP-EFV-NPs were
      incorporated into a thermosensitive gel (CAP-EFV-NP-Gel). CAP-EFV-NPs, CAP-EFV-NP
      Gel and efavirenz solution were evaluated for cytotoxicity to HeLa cells and for
      in vitro short-term (1-day) and long-term (3-day) prophylaxis against HIV-1
      infection in TZM-bl cells. CAP-EFV-NPs had size < 100 nm, negative surface charge
      and encapsulation efficiency of efavirenz was > 98%. CAP-EFV-NPs and CAP-EFV-NP
      Gel were significantly less toxic (P < 0.01) to HeLa cells as compared to
      efavirenz solution. CAP-EFV-NPs showed significantly higher prophylactic activity
      (P < 0.01) against HIV-1 infection to TZM-bl cells as compared to efavirenz
      solution and blank CAP nanoparticles. CAP-EFV-NP-Gel can be a promising nano
      microbicide for long-term HIV prophylaxis.

PMID- 26307826
TI  - Controlled Dual Drug Release and In Vitro Cytotoxicity of Electrospun Poly(lactic
      co-glycolic acid) Nanofibers Encapsulated with Micelles.
AB  - In order to realize controlled dual release of two hydrophobic drugs with
      distinct rates in a vehicle, novel poly(lactic-co-glycolic acid) (PLGA) composite
      nanofibers encapsulated with micelles were successfully fabricated by "emulsion
      electrospinning." Brefeldin A (BFA) was firstly embedded in monomethoxy
      poly(ethylene glycol)-b-poly(L-lactide) (MePEG-PLLA) micelles. By means of
      "emulsion-electrospinning," paclitaxel (PTX) and polymeric micelles contained BFA
      were successfully loaded into the electrospun PLGA composite nanofibers. The in
      vitro release results demonstrated that the location of the drugs in the
      electrospun fibers determined their release profiles. BFA had a long-term and
      sustained release while PTX had a relatively rapid release in the dual drugs
      delivery system. In vitro cytotoxicity studies revealed that the composite
      nanofibers with two drugs restrained HepG-2 cells more efficiently. These results
      strongly suggested that the electrospun composite nanofibers containing polymeric
      micelles can be used as an effective controlled dual release of hydrophobic drugs
      and were suitable for postoperative chemotherapy of cancers.

PMID- 26307827
TI  - Development of RGD-Functionalized PEG-PLA Micelles for Delivery of Curcumin.
AB  - Curcumin (Cur), a hydrophobic polyphenolic compound, possesses a wide range of
      biological activities. However, its prominent application in cancer treatment is
      limited due to low aqueous solubility and rapid metabolism. Recently, micelle
      based drug delivery system has been proven to be an attractive alternative for
      poorly soluble drugs. In order to improve the application of Cur as an anti
      cancer agent, in this study, we synthesized the alphavbeta3 integrin-targeted
      peptide (RGD) functionalized polymer (RGD-PEG-PLA). The RGD conjugated Cur loaded
      micelles (Cur-RPP) were prepared using the thin-film hydration method with
      modification and the preparation process was optimized with a central composite
      design. The obtained Cur-RPP presented spherical shape with a particle size of 20
      nm and high drug loading (4.70%). Compared with the Cur propylene glycol
      solution, the in vitro release of Cur from the prepared micelles showed the
      sustained-release property. Cellular uptake of Cur-RPP was found to be higher
      than that of non-RGD modified micelles due to the binding effect between
      alphavbeta3 integrin and RGD in human umbilical vein endothelial cells (HUVEC)
      and mouse melanoma cell lines (B16). In B16 tumor-bearing mice, Cur-RPP showed
      the stronger inhibiting effect on growth of tumor compared with non-RGD modified
      micelles. It could be concluded from these results that the RGD modified micelles
      might be a potential carrier for Cur.

PMID- 26307828
TI  - Evaluation of In-Situ Magnetic Signals from Iron Oxide Nanoparticle-Labeled PC12
      Cells by Atomic Force Microscopy.
AB  - The magnetic signals from magnetite nanoparticle-labeled PC12 cells were assessed
      by magnetic force microscopy by deploying a localized external magnetic field to
      magnetize the nanoparticles and the magnetic tip simultaneously so that the
      interaction between the tip and PC12 cell-associated Fe3O4 nanoparticles could be
      detected at lift heights (the distance between the tip and the sample) larger
      than 100 nm. The use of large lift heights during the raster scanning of the
      probe eliminates the non-magnetic interference from the complex and rugged cell
      surface and yet maintains the sufficient sensitivity for magnetic detection. The
      magnetic signals of the cell-bound nanoparticles were semi-quantified by
      analyzing cell surface roughness upon three-dimensional reconstruction generated
      by the phase shift of the cantilever oscillation. The obtained data can be used
      for the evaluation of the overall cellular magnetization as well as the maximum
      magnetic forces from magnetic nanoparticle-labeled cells which is crucial for the
      biomedical application of these nanomaterials.

PMID- 26307829
TI  - Enhancement of Solubility, Transport Across Madin-Darby Canine Kidney Monolayers
      and Oral Absorption of Pranlukast Through Preparation of a Pranlukast
      Phospholipid Complex.
AB  - This study aimed to enhance the solubility of a poorly water-soluble drug,
      pranlukast, as well as its transport across Madin-Darby canine kidney (MDCK)
      monolayers, thus increasing its oral bioavailability. To accomplish this aim, we
      prepared a pranlukast-phospholipid complex (PPC). The PPC was prepared by solvent
      evaporation and characterized by transmission electron microscopy (TEM), X-ray
      diffraction (XRD), infrared (IR) spectroscopy, and solubilization studies. The
      solubility of pranlukast in the PPC was increased from 1.03 +/- 0.32 MUg/ml to
      160.63 +/- 2.72 MUg/ml with a yield of 96.39 +/- 1.20% when the PPC was prepared
      under optimal conditions. TEM images showed that the PPC particles had a
      spherical shape. XRD data indicated that pranlukast in the PPC was either in an
      amorphous form or in a dispersed molecular distribution. IR analysis confirmed
      the interaction between pranlukast and the phospholipids. The transport mechanism
      of the PPC and non-complexed pranlukast across MDCK cells was measured and was
      observed to be significantly greater for the former than for the latter. The in
      vivo bioavailability of the PPC in rats hastened the onset of pranlukast-induced
      therapeutic effects, with C(max) and AUC increases of 21.88- and 28.64-fold,
      respectively, compared with raw crystals. In addition, an in vivo imaging method
      was used to corroborate that the PPC exhibited rapid circulatory distribution and
      gastrointestinal tract accumulation. These results indicate that PPC appears to
      be a promising drug delivery system for pranlukast, improving drug absorption and
      decreasing side effects by reducing the required oral dose.

PMID- 26307830
TI  - Chemical Radiosensitivity of DNA Induced by Gold Nanoparticles.
AB  - Gold nanoparticles (GNPs) sensitize biomolecules to radiation in two ways: by
      locally increasing the radiation energy absorbed and by modifying the sensitivity
      of the target biomolecules to radiation. Taking DNA as the biological target, we
      present the first investigation of the latter chemical mechanism of
      radiosensitization by irradiating thin films made of GNP-DNA complexes with 10 eV
      electrons. Naked GNPs of 5 and 15 nm diameters were synthesized and
      electrostatically bound to DNA. Damage to the GNP-DNA complexes were analyzed, as
      a function of electron fluence, by electrophoresis. In identical 5-monolayer
      films, the yield of DNA damage, as well as the enhancement factor due to the
      presence of 5 nm positively-charged nanoparticles, increased with rising ratio of
      GNPs to DNA up to 1:1. In comparison, increasing the ratio of negatively-charged
      15 nm GNPs to DNA did not increase damage. As verified by XPS and zeta potential
      measurements, the binding of plasmid DNA to the surface of the two sizes of GNPs
      varies owing to the characteristics of the GNP surface and electrostatic
      interaction. The results indicate that strong binding of GNPs to DNA could
      significantly influence the efficiency of the chemical radiosensitization
      mechanism. This mechanism appears to be an important component of the overall
      process of GNP radiosensitization and should be considered when modeling this
      phenomenon. Our results suggest that small size GNPs (diam. <= 5 nm) are more
      efficient radiosensitizers compared to larger GNPs when delivered into cancerous
      cells, where their action should be cell-cycle dependent.

PMID- 26307831
TI  - Chitosan-Modified Cationic Amino Acid Nanoparticles as a Novel Oral Delivery
      System for Insulin.
AB  - In this study, chitosan-modified basic amino acid derivatives were explored as
      novel absorption enhancers and nanocarriers for oral insulin delivery. N-Arginine
      chitosan (ACS) and N-histidine-chitosan (HCS) were successfully synthesized, and
      their polyelectrolyte complexes (PECs) with insulin were formed by the ordinary
      self-assembly method. The obtained PECs exhibited a spherical morphology with a
      narrow size of 205-303 nm, positive surface charge (zeta potential + 14- + 27 mV)
      and encapsulation efficiency of approximately 80%. The electrostatic interactions
      between chitosan derivatives and insulin were confirmed by molecular modeling
      simulation. In vitro studies demonstrated that PECs could partially protect
      insulin from proteolysis and degradation at 50 degrees C for at least 6 h.
      Compared with the insulin solution, internalization of PECs into Caco-2 cells was
      increased by up to 20.7-fold. Moreover, permeability was enhanced as the degrees
      of substitution of arginine and histidine increased. The PECs had in vivo
      pharmacological activities of 2.29%-5.39%, with a significant reduction of blood
      glucose levels in diabetic rats. These results suggested that ACS and HCS PECs
      hold promising potential for the oral delivery of insulin, peptides and proteins.

PMID- 26307832
TI  - Solid Lipid Nanoparticles as Non-Viral Vectors for Gene Transfection in a Cell
      Model of Fabry Disease.
AB  - Here, we demonstrate the ability of solid lipid nanoparticle-based non-viral
      vectors to increase the alpha-galactosidase A levels of the IMFE1 cell line, an
      in vitro model for target cells in Fabry disease. For this purpose, vectors
      containing the pR-M10-alphaGal A plasmid, which encodes the alpha-galactosidase A
      enzyme, were prepared; the in vitro transfection efficacy was studied in IMFE1
      cells, and the results were confirmed by RT-PCR. The cellular uptake of the
      vectors, intracellular disposition of the plasmid, and probable endocytosis
      pathways of the nanoparticles were also analyzed. The vectors used for the
      studies carried protamine (P-DNA-SLN), dextran and protamine (D-P-DNA-SLN), or
      hyaluronic acid of two different molecular weights and protamine (HA150-P-DNA-SLN
      or HA500-P-DNA-SLN). The new formulations, which presented a particle size in the
      range of nanometers (from 218 nm to 348 nm) and a positive superficial charge,
      were able to increase alpha-galactosidase A activity up to 4-fold in comparison
      to non treated IMFE1 cells. The most efficient vectors were those that included
      HA, and no differences due to changes in the molecular weight of HA were
      detected. The observed lack of colocalization with each of the four different
      Nile Red-labeled vectors and transferrin or cholera toxin appears to indicate
      that clathrin- and caveolae-independent pathways may be involved in their
      cellular uptake. Additionally, colocalization with LysoTracker indicated that the
      formulations were exposed to lysosomal activity, which may be responsible for the
      release of the plasmid from the vector. In conclusion, we reveal the potential of
      SLN-based vectors to efficiently transfect an immortalized Fabry patient cell
      line.

PMID- 26307833
TI  - Topographic Cue from Electrospun Scaffolds Regulate Myelin-Related Gene
      Expressions in Schwann Cells.
AB  - Matured Schwann cells play a vital role in promoting regeneration and restoration
      of functional peripheral nervous tissue. In the present study, two dimensional
      film, three dimensional random and longitudinally aligned electrospun fibers of
      poly(lactide-co-glycolide) were used to evaluate the effect of topography on
      expressions of myelin related genes. The aligned nanofibrous scaffold
      demonstrated significant increase in Schwann cell adhesion using after 3, 6 and
      12 hours of culture compared to the film and random fibers. Cell morphology,
      degree of orientation and elongation factor evaluated using a scanning electron
      microscope revealed that cells on aligned scaffold have spindle morphology,
      whereas cells on random and two dimensional films favor spherical morphology
      confirming the effect of topography. Significant increase in elongation factor
      was observed in aligned scaffold as compared to film and random fibers (p <
      0.05). The gene expression analysis revealed that aligned scaffold significantly
      up-regulated the expression of early myelination markers: myelin-associated
      glycoprotein and myelin protein zero, cell adhesion molecule: neural cadherin,
      extracellular matrix molecule: neurocan, as well the down-regulation of non
      myelinating Schwann cell marker: neural cell adhesion molecule when compared to
      random and film (p < 0.05). The gene expression patterns of aligned fibers favor
      myelination of Schwann cells when compared to film and random fibers. Thus, our
      results demonstrate that the aligned topography of the scaffold promotes
      maturation of Schwann cells and thereby its myelination to maintain its
      functionality.

PMID- 26307834
TI  - Effects of the Surface Charge of Stem Cell Membranes and DNA/Polyethyleneimine
      Nanocomplexes on Gene Transfection Efficiency.
AB  - In this work, we examined the effects of the surface charge of stem cell
      membranes and DNA/polyethyleneimine (PEI) nanocomplexes on gene transfection
      efficiency, because PEI was one of the most reliable and efficient carriers, and
      rat bone marrow mesenchymal stem cells (rBMSCs) and rat muscle-derived stem cells
      (rMDSCs) were one of the readily accessible and plentiful sources of stem cells.
      Thus, we compared the efficiency of DNA transfection in rBMSCs and rMDSCs using
      the PEI as a gene carrier. Transfection efficiency was evaluated on the basis of
      electrostatic interaction between negatively charged stem cell membranes and
      positively charged DNA/PEI nanocomplexes. DNA was fully complexed with PEI at
      negative-to-positive (NIP) charge ratios greater than 2, as confirmed by gel
      electrophoresis and fluorescence measurements. DNA and PEI formed spherical
      nanocomplexes ranging in diameter from 150 nm to 500 nm. The positive surface
      charge of DNA/PEI nanocomplexes increased with an increasing N/P charge ratio, as
      measured using dynamic light scattering and a single-walled carbon nanotube-based
      field-effect transistor device. rBMSCs and rMDSCs both carried a negative surface
      charge, with rBMSCs being more negatively charged. The transfection efficiency of
      rMDSCs measured using DNA/PEI nanocomplexes was very low (1%-5%) at most of the
      N/P charge ratios tested, whereas better efficiencies were observed with rBMSCs
      (1%-17%). Nanocomplexes with high NIP charge ratios were cytotoxic to both rBMSCs
      and rMDSCs. Collectively, the results indicate that rBMSCs were more effectively
      transfected with DNA/PEI nanocomplexes than were rMDSCs, reflecting the higher
      negative charge of rBMSC membranes that facilitate the interaction with
      positively charged DNA/PEI nanocomplexes.

PMID- 26307835
TI  - Particle Systems for Stem Cell Applications.
AB  - Stem cells have been widely investigated for regeneration of aged, injured, or
      diseased tissues. Although they have remarkable potential in clinical
      applications, some critical issues must be addressed, one of which being the poor
      control of their fates in vivo. A variety of particles, typically the organic and
      inorganic materials, liposomes, and polyplexes, provides multiple functionalities
      of labeling and tracking of the transplanted stem cells, and versatile
      capabilities of intracellular delivery of biomolecules for stem cell control in
      vivo. In this report, major applications of different particle systems are
      reviewed on the topics of tracking transplanted stem cells and labeling of
      endogenous stem cells in vivo. Detailed discussions are provided on recent
      advances of the particle-assisted intracellular delivery of biomolecules to stem
      cells for in vivo applications. Some novel particle-carriers are reported on stem
      cell transplantation and drug delivery for cancer therapy. Also discussed are
      critical challenges and future directions in the development of particle carriers
      for stem cell applications.

PMID- 26307836
TI  - Role of Mesoporous Wollastonite (Calcium Silicate) in Mesenchymal Stem Cell
      Proliferation and Osteoblast Differentiation: A Cellular and Molecular Study.
AB  - Wollastonite (calcium silicate) has been widely used in bone tissue engineering,
      but its mechanism of action on the regulation of mesenchymal stem cell
      proliferation and differentiation to osteoblasts still remains unclear. The
      current study utilized an inexpensive source of rice straw ash to synthesize
      wollastonite with mesoporous architecture. Mesoporous-wollastonite (m-WS)
      particles were characterized by transmission electron microscopy (TEM), N2
      adsorption-desorption isotherms, and Fourier transform infrared (FT-IR)
      spectroscopy. These particles were found to be biocompatible with mouse
      mesenchymal stem cells (C3H10T1/2) and significantly stimulated cell
      proliferation by promoting the entry of the cell population from the G0/G1 phase
      into the S and G2/M phases via the upregulated expression of the cyclin B1 and
      cyclin E genes. Under osteogenic conditions, m-WS particles promoted osteoblast
      differentiation as indicated by calcium deposits and upregulated mRNA expression
      of osteoblast differentiation marker genes determined by real-time RT-PCR,
      depicting the osteoconductive nature of these particles. Runx2, a bone-specific
      transcription factor responsible for the expression of osteoblast differentiation
      marker genes, was upregulated in C3H10T1/2 cells. The expression of Runx2 co
      regulators like Sirt-1, a positive regulator, and HDAC-4, a negative regulator,
      were upregulated and downregulated, respectively, by m-WS particles in these
      cells. Thus, this study provides a detailed insight into the effect of m-WS
      particles on mesenchymal stem cells at the molecular and cellular levels for in
      vitro bone formation.

PMID- 26307837
TI  - Application of C60 Fullerene-Doxorubicin Complex for Tumor Cell Treatment In
      Vitro and In Vivo.
AB  - Development of nanocarriers for effective drug delivery to molecular targets in
      tumor cells is a real problem in modern pharmaceutical chemistry. In the present
      work we used pristine C60 fullerene as a platform for delivery of anticancer drug
      doxorubicin (Dox) to its biological targets. The formation of a complex of C60
      fullerene with Dox (C60 + Dox) is described and physico-chemical characteristics
      of such complex are presented. It was found that Dox conjugation with C60
      fullerene leads to 1.5-2-fold increase in Dox toxicity towards various human
      tumor cell lines, compared with such effect when the drug is used alone.
      Cytotoxic activity of C60 + Dox complex is accompanied by an increased level of
      cell produced hydrogen peroxide at early time point (3 h) after its addition to
      cultured cells. At the same time, cellular production of superoxide radicals does
      not change in comparison with the effect of Dox alone. Cytomorphological studies
      have demonstrated that C60 + Dox complexes kill tumor cells by apoptosis
      induction. The results of in vivo experiments using Lewis lung carcinoma in mice
      confirmed the enhancement of the Dox toxicity towards tumor cells after drug
      complexation with C60 fullerene. The effect of such complex towards tumor-bearing
      mice was even more pronounced than that in the in vitro experiment with targeting
      human tumor cells. The tumor volume decreased by 2.5 times compared with the
      control, and an average life span of treated animals increased by 63% compared
      with control. The obtained results suggest a great perspective of application of
      C60 + Dox complexes for chemotherapy of malignant tumors.

PMID- 26307838
TI  - Evaluation of rMETase-Loaded Stealth PLGA/Liposomes Modified with Anti-CAGE scFV
      for Treatment of Gastric Carcinoma.
AB  - Stealth PLGA/Liposome nanoparticles (NPs) modified with tumor-targeting single
      chain antibody fragment (scFV-P/L) for systemic delivery of recombinant
      methioninase (rMETase) for gastric cancer were prepared. The morphologies and
      therapeutic effects of rMETase-loaded scFV-P/L (scFV-rMETase-P/L) in vitro were
      analyzed. Functional scFV-P/L NPs composed of PLGA, DOPC and DSPE-PEG display low
      cell cytoxicity in SGC-7901 cells, and has more cell uptake ability than P/L NPs.
      scFV-rMETase-P/L was more effective in inhibiting tumor growth in the
      subcutaneous gastric carcinoma tumor model than free rMETase in solution (p <
      0.05) and rMETase-loaded P/L (rMETase-P/L) (p < 0.05). Our findings collectively
      support the utility of scFV-targeted P/L NPs as a potentially effective drug
      delivery system.

PMID- 26307839
TI  - Uptake of Gold Nanoparticles in Breathless (Hypoxic) Cancer Cells.
AB  - Gold nanoparticles (GNPs) are emerging as promising novel agents for cancer
      therapy. However, the oxygen concentration in human tumors is highly
      heterogeneous, and there are many regions with very low levels of oxygen
      (hypoxia). A majority of solid tumors contain regions with oxygen pressure values
      of less than 0.7% in the gas phase. The purpose of this study was to investigate
      NP stability, toxicity, and cellular uptake under hypoxic conditions. GNPs 50 nm
      in diameter were used, and the experiment was performed under 0.2% (hypoxic) and
      21% (normoxic) oxygen levels using MCF-7 and HeLa cells. Hypoxic cells with
      prolonged exposure (eighteen hours) to hypoxia had a higher NP uptake at both 6-
      and 24-hour NP incubation time points. No significant toxicity was introduced by
      NPs under hypoxic and normoxic conditions. These findings will play a vital role
      in the optimization of GNP-based therapeutics in cancer treatment.

PMID- 26307840
TI  - Improving Anti-Tumor Activity of Curcumin by Polymeric Micelles in
      Thermosensitive Hydrogel System in Colorectal Peritoneal Carcinomatosis Model.
AB  - In this work, we prepared an in situ gel-forming composite drug delivery system
      (DDS) to treat colorectal peritoneal carcinomatosis. The composite DDS was based
      on curcumin loaded polymeric micelles (Cur-M) and thermosensitive hydrogel. Cur-M
      had a particle size of 27.1 +/- 1.3 nm with polydisperse index of 0.149 +/-
      0.017, and the drug loading and encapsulation efficiency of Cur-M were 14.82 +/-
      0.07 and 98.83 +/- 0.45%, respectively. The prepared Cur-M in thermosensitive
      hydrogel system (Cur-H) was a free-flowing sol at ambient temperature, and
      converted into non-flowing gel at body temperature, serving as a drug depot. In
      vitro drug release behavior suggested that Cur-H and Cur-M could release Cur in
      an extent period, and Cur-H showed a slower cumulative release rate. In addition,
      compared with free Cur, Cur-M showed higher cytotoxicity and apoptotic induction
      efficiency. Furthermore, colorectal peritoneal carcinomatosis mouse model was
      used to evaluate the anti-tumor activity of Cur-H, and the results suggested that
      Cur-H could inhibit tumor growth and metastasis, and prolonged survival of tumor
      bearing mice. Immunohistochemical and immunofluorescent staining of tumor tissues
      in each group were conducted. The results demonstrated that tumors in Cur-H group
      showed lower proliferation activity, more apoptotic cells, and fewer
      microvessels. Besides, pharmacokinetic studies of Cur-H and Cur-M by
      intraperitoneal administration were performed. Compared with Cur-M, Cur-H showed
      a higher AUC and longer t1/2. Thus, the above results suggested that Cur-H may
      have potential applications in colorectal peritoneal carcinomatosis.

PMID- 26307841
TI  - Therapeutic Ultrasound Contrast Agents for the Enhancement of Tumor Diagnosis and
      Tumor Therapy.
AB  - The functionality of ultrasound in early cancer detection is limited because of
      its relatively low contrast resolution. Because it has a high degree of
      echogenicity, a microbubble contrast agent is often used to overcome this
      intrinsic limitation of imaging at low-contrast resolution. A targeted and drug
      loaded microbubble contrast agent for simultaneous diagnosis and therapy has
      recently been investigated. However, no optimized theragnosis ultrasound
      microbubbles have been developed. Paclitaxel (PTX)-encapsulating human serum
      albumin nanoparticles (PTX-HSA-NPs) were conjugated onto an ultrasound
      microbubbles (PTX-HSA-NPs-MBs) fabricated in the laboratory to result in a narrow
      size distribution (1.7 +/- 0.7 MUm) and an optimal resonance frequency of 3 MHz.
      After intravenous injection of HSA-NPs-MBs, echogenicity in the tumor xenografted
      with breast cancer MCF-7 cells was significantly enhanced, showing the
      possibility of early cancer diagnosis. Mice injected with PTX-HSA-NPs-MBs showed
      higher survival rates in comparison with control groups, demonstrating the
      possibility of theragnosis. In the present study, the conjugation of PTX-HSA-NPs
      onto the ultrasound microbubbles simultaneously provided (1) enhanced ultrasound
      signal generation, (2) sufficient drug-loading capacity, (3) ability to deliver
      drugs to a preferred tumor site, and (4) increased stability in blood
      circulation.

PMID- 26307842
TI  - Biodegradable Core-Shell Copolymer-Phospholipid Nanoparticles for Combination
      Chemotherapy: An In Vitro Study.
AB  - In the present study, we developed novel core-shell-type lipid/particle
      assemblies comprising poly(lactic-co-glycolic acid) nanoparticle cores coated
      with a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine shell. Hydrophobic
      dihydroartemisinin and hydrophilic doxorubicin were co-loaded in the core-shell
      type lipid/particle assemblies for combination chemotherapy. The physicochemical
      properties of the dual drug-loaded core-shell-type lipid/particle assemblies were
      characterized. The results of colorimetric cell viability assay and cellular
      uptake experiments demonstrated that the lipid/particle hybrid could increase the
      accumulation of doxorubicin accumulation in cell nuclei, thus enhancing cell
      cytotoxicity. This effect contributed to the high treatment efficiency of
      dihydroartemisinin and doxorubicin. These biodegradable lipid/polymer hybrid
      particles could be promising delivery systems to improve combination
      chemotherapy.

PMID- 26307843
TI  - Anti-Mesothelin Nanobodies for Both Conventional and Nanoparticle-Based
      Biomedical Applications.
AB  - Mesothelin, a cancer biomarker overexpressed in tumors of epithelial origin, is a
      target for nanotechnology-based diagnostic, therapeutic, and prognostic
      applications. The currently available anti-mesothelin antibodies present
      limitations, including low penetration due to large size and/or lack of in vivo
      stability. Single domain antibodies (sdAbs) or nanobodies (Nbs) provide powerful
      solutions to these specific problems. We generated a phage-display library of Nbs
      that were amplified from B cells of a llama that was immunized with human
      recombinant mesothelin. Two nanobodies (Nb A1 and Nb C6) were selected on the
      basis of affinity (K(D) = 15 and 30 nM, respectively). Nb A1 was further modified
      by adding either a cysteine to permit maleimide-based bioconjugations or a
      sequence for the site-specific metabolic addition of a biotin in vivo. Both
      systems of conjugation (thiol-maleimide and streptavidin/biotin) were used to
      characterize and validate Nb A1 and to functionalize nanoparticles. We showed
      that anti-mesothelin Nb A1 could detect native and denatured mesothelin in
      various diagnostic applications, including flow cytometry, western blotting,
      immunofluorescence, and optical imaging. In conclusion, anti-mesothelin Nbs are
      novel, cost-effective, small, and single domain reagents with high affinity and
      specificity for the tumor-associated antigen mesothelin, which can be simply
      bioengineered for attachment to nanoparticles or modified surfaces using multiple
      bioconjugation strategies. These anti-mesothelin Nbs can be useful in both
      conventional and nanotechnology-based diagnostic, therapeutic and prognostic
      biomedical applications.

PMID- 26307844
TI  - Downstream Processing, Formulation Development and Antithrombotic Evaluation of
      Microbial Nattokinase.
AB  - The present research work describes the downstreaming of nattokinase (NK)
      produced by Bacillus subtilis under solid state fermentation; and the role of
      efficient oral formulation of purified NK in the management of thrombotic
      disorders. Molecular weight of purified NK was estimated to be 28 kDa with
      specific activity of 504.4 FU/mg. Acid stable nattokinase loaded chitosan
      nanoparticles (sNLCN) were fabricated for oral delivery of this enzyme. Box
      Behnken design (BBD) was employed to investigate and validate the effect of
      process (independent) variables on the quality attributes (dependent variables)
      of nanoparticles. The integrity, conformational stability and preservation of
      fibrinolytic activity of NK (in both free and sNLCN forms) were established by
      SDS-PAGE, CD analysis and in vitro clot lytic examination, respectively. A 'tail
      thrombosis model' demonstrated significant decrease in frequency of thrombosis in
      Wistar rats upon peroral administration of sNLCN in comparison with negative
      control and free NK group. Furthermore, coagulation analysis, namely the
      measurement of prothrombin and activated partial thromboplastin time illustrated
      that sNLCN showed significantly (p < 0.001) higher anti-thrombotic potential in
      comparison to the free NK. Further, sNLCN showed anti-thrombotic profile similar
      to warfarin. This study signifies the potential of sNLCN in oral delivery of NK
      for the management of thrombotic disorders.

PMID- 26307845
TI  - Joint Surface-Active Phospholipid-Mimetic Liposomes for Intra-Articular Delivery
      of Paclitaxel.
AB  - Synovial inflammation, angiogenesis and joint degradation are the hallmarks of
      inflammatory arthritis progression. Angiostatic targeting is an extensively
      studied potential therapeutic option for inflammatory arthritis. Studies have
      confirmed that surface-active phospholipids (SAPLs), predominantly
      phosphatidylcholines (PCs), are responsible for the lubricating properties of
      lubricin in joints. Paclitaxel, a potent antineoplastic agent in cancer
      chemotherapy, has been shown to inhibit several processes associated with
      arthritis development such as angiogenesis, neutrophil activation and collagenase
      expression but is limited by systemic toxicity. This study was aimed at designing
      a surface-active phospholipid mimetic nanocarrier system and assessing its
      efficacy for intra-articular delivery of paclitaxel in rat joints. Dipalmitoyl-sn
      glycero-3-phosphatidylcholine (DPPC) liposomes were prepared using a thin-film
      hydration method and characterized for size, morphology, drug encapsulation and
      in vitro release. DPPC liposomes of a size of 311 +/- 57 nm and 92 +/- 0.6%
      paclitaxel encapsulation were developed. In vitro release studies showed a short
      initial burst phase and a sustained release profile with a cumulative release of
      18 +/- 0.36% of the drug by 60 h in phosphate-buffered saline (PBS). The efficacy
      of the intra-articular formulation was evaluated in antigen-induced arthritic rat
      models and compared with direct injections of paclitaxel. After a 28-day period,
      intra-articular paclitaxel delivered in liposomes led to a significant
      improvement in gait scores and synovial inflammation in rats compared to the
      control, as seen in histopathology studies. Reduction in inflammation in the
      experimental group was confirmed by evaluating TNFalpha levels in serum samples.
      This study suggests feasibility of using surface-active phospholipid based
      carriers for local, intra-articular therapy of paclitaxel in arthritis.

PMID- 26307846
TI  - Towards the Design of 3D Fiber-Deposited Poly(epsilon-caprolactone)/lron-Doped
      Hydroxyapatite Nanocomposite Magnetic Scaffolds for Bone Regeneration.
AB  - In the past few years, researchers have focused on the design and development of
      three-dimensional (3D) advanced scaffolds, which offer significant advantages in
      terms of cell performance. The introduction of magnetic features into scaffold
      technology could offer innovative opportunities to control cell populations
      within 3D microenvironments, with the potential to enhance their use in tissue
      regeneration or in cell-based analysis. In the present study, 3D fully
      biodegradable and magnetic nanocomposite scaffolds for bone tissue engineering,
      consisting of a poly(epsilon-caprolactone) (PCL) matrix reinforced with iron
      doped hydroxyapatite (FeHA) nanoparticles, were designed and manufactured using a
      rapid prototyping technique. The performances of these novel 3D PCL/FeHA
      scaffolds were assessed through a combination of theoretical evaluation,
      experimental in vitro analyses and in vivo testing in a rabbit animal model. The
      results from mechanical com- pression tests were consistent with FEM simulations.
      The in vitro results showed that the cell growth in the magnetized scaffolds was
      2.2-fold greater than that in non-magnetized ones. In vivo experiments further
      suggested that, after only 4 weeks, the PCL/FeHA scaffolds were completely filled
      with newly formed bone, proving a good level of histocompatibility. All of the
      results suggest that the introduction of magnetic features into biocompatible
      materials may confer significant advantages in terms of 3D cell assembly.

PMID- 26307847
TI  - Novel Simvastatin-Loaded Nanoparticles Based on Cholic Acid-Core Star-Shaped PLGA
      for Breast Cancer Treatment.
AB  - A novel nanocarrier system of cholic acid (CA) core, star-shaped polymer
      consisting of poly(D,L-lactide-co-glycolide) (PLGA) was developed for sustained
      and controlled delivery of simvastatin for chemotherapy of breast adenocarcinoma.
      The star-shaped polymer CA-PLGA with three branch arms was synthesized
      successfully through the core-first approach. The simvastatin-loaded star-shaped
      CA-PLGA nanoparticles were prepared through a modified nanoprecipitation method.
      The data showed that the fluorescence star-shaped CA-PLGA nanoparticles could be
      internalized into MDA-MB-231 and MDA-MB-468 human breast cancer cells. The
      simvastatin-loaded star-shaped CA-PLGA nanoparticles achieved significantly
      higher level of cytotoxicity than pristine simvastatin and simvastatin-loaded
      linear PLGA nanoparticles. Moreover, the expression of the cell cycle protein
      cyclin D1 was dramatically inhibited by simvastatin in both cells, with
      simvastatin-loaded star-shaped CA-PLGA nanoparticles having the greatest effect.
      MDA-MB-231 xenograft tumor model on BALB/c nude mice showed that simvastatin
      loaded star-shaped CA-PLGA nanoformulations could effectively inhibit the growth
      of tumor over a longer period of time than pristine simvastatin and simvastatin
      loaded linear PLGA nanoformulations at the same dose. In agreement with these,
      the nuclear expression of proliferation marker Ki-67 in simvastatin-loaded star
      shaped CA-PLGA nanoparticles group was reduced to a most extent among four groups
      through tumor frozen section immunohistochemistry. In conclusion, the star-shaped
      CA-PLGA polymers could serve as a novel polymeric nanocarrier for breast cancer
      chemotherapy.

PMID- 26307848
TI  - Fullerenols and Fullerene Alter Cell Growth and Metabolisms of Escherichia coli.
AB  - Fullerenes are exciting chemicals having great promise in biomedical
      applications. The toxicity of these nanoparticles on organism's metabolism
      remains a longstanding challenge in biomedical science. Toward this objective, we
      explored the interaction of two commonly used fullerene species, nano-C60 and
      fullerenols, with bacterial cells and their impact on cell growth and metabolism
      using Escherichia coli under aerobic and anaerobic conditions. Results revealed
      that fullerenol interactions could promote cell growth and affect cellular
      metabolism significantly. Here we report potent inhibition of the ethanol
      generation caused by fullerenols. In comparison, nano-C60 interaction can hardly
      affect ethanol production and other bacterial activities. Enzyme assay studies
      suggested that the inhibition of ethanol generation was not due to the gene
      regulation. These data implicated the application of fullerenols could have
      considerable impact on cell growth, and enzymatic and metabolic performance of
      Escherichia coli.

PMID- 26307849
TI  - Enhanced Percutaneous Delivery of 1,1-bis(3'-indolyl)-1-(p-chlorophenyl) Methane
      for Skin Cancer Chemoprevention.
AB  - Skin cancer has high incidence in the United States and is mainly caused by
      ultraviolet B (UVB) radiation. In this study, we demonstrated the role of 1,1
      bis(3'-indolyl)-1-(p-chlorophenyl) methane (DIM-D) in the prevention of skin
      photocarcinogenesis using an in vivo UVB-induced skin cancer model. We also
      evaluated the efficiency of oleic acid-modified nanostructured lipid carriers to
      deliver DIM-D across the skin barrier into the epidermis for chemopreventive
      activity. Nanocarriers were 203.00 +/- 21.21 nm in diameter with polydispersity,
      zeta potential and entrapment efficiency of 0.33 +/- 0.01, 37.17 +/- 0.90 mV and
      93.64 +/- 0.65%, respectively. Oleic acid-modified nanocarriers were incorporated
      into Hydroxypropyl methylcellulose to form DIM-D-Nanogel (DIM-D-N). DIM-D-N
      pretreatment prior to UVB exposure delayed tumor initiation and reduced tumor
      multiplicity (p < 0.05) at the end of the study compared to Epigallocatechin
      gallate (EGCG) gel pretreatment. DIM-D-N pretreatment decreased UVB-induced
      damage to skin lipids and proteins (p < 0.05), respectively by 7.63 and 2.56-fold
      less than EGCG gel pretreatment and by 17.86 and 11.92-fold less than UVB-only
      treatment. Histology showed rete-ridge extension, epidermal thickening and
      hyperkeratosis for UVB-only treatment and EGCG gel pretreatment; DIM-D-N
      pretreatment showed similar features as the negative control. Western blot
      analysis showed increased Nurr1 expression (p < 0.05) for DIM-D-N pretreated
      group compared to EGCG gel (4.68-fold). DIM-D-N pretreatment reduced BCI-2
      expression (p < 0.05) but increased Bax and cPARP. Knock down studies with Nurr1
      siRNA reduced the expressions of Nurr1 and cPARP by 8.18 and 1.45-fold,
      respectively (p < 0.05). Our results suggest the role of DIM-D in skin cancer
      chemoprevention mediated by possible molecular therapeutic targets such as Nurr1.

PMID- 26307851
TI  - Strength and Power Development in Professional Rugby Union Players Over a
      Training and Playing Season.
AB  - PURPOSE: To investigate strength and power development in elite rugby players
      during the different phases of a professional season. METHODS: Sixteen
      professional rugby union athletes from an English premiership team were monitored
      for measures of lower-body peak force, force at 50 ms, force at 100 ms (all
      isometric squat), and power (explosive hack squat). Athletes were assessed at the
      start of preseason (T1), postpreseason (T2), midway through the competitive
      season (T3), and at the end of the competitive season (T4). Effect-size (ES)
      statistics with magnitude-based inferences were calculated to interpret
      differences in physical performance between the different stages of the season.
      RESULTS: Very likely beneficial increases in force at 50 ms (+16%, ES = 0.75 +/-
      0.4) and 100 ms (+14%, ES = 0.63 +/- 0.4) were observed between T1 and T2. A
      likely beneficial increase in power was observed between T2 and T3 (+4%, ES =
      0.31 +/- 0.2). Between T3 and T4, decreases in force at 50 ms (-6%, ES = -0.39 +/
      0.3) and 100 ms (-9%, ES = -0.52 +/- 0.4) occurred, while peak force and power
      were maintained. Over the full season (T1-T4) clear beneficial increases in all
      measures of strength and power were identified. CONCLUSIONS: Meaningful increases
      in strength and power can be achieved in professional English premiership rugby
      players over a full playing season. The greatest opportunity for strength and
      power development occurs during pre- to midseason phases, while these measures
      are maintained or decrease slightly during the latter stages of a season.

PMID- 26307850
TI  - Organic Food Consumption during Pregnancy and Hypospadias and Cryptorchidism at
      Birth: The Norwegian Mother and Child Cohort Study (MoBa).
AB  - BACKGROUND: The etiologies of the male urogenital anomalies hypospadias and
      cryptorchidism remain unclear. It has been suggested that maternal diet and
      environmental contaminants may affect the risk of these anomalies via placental
      or hormonal disturbances. OBJECTIVES: We examined associations between organic
      food consumption during pregnancy and prevalence of hypospadias and
      cryptorchidism at birth. METHODS: Our study includes 35,107 women participating
      in the Norwegian Mother and Child Cohort Study (MoBa) who delivered a singleton
      male infant. Information about use of six groups of organically produced food
      (vegetables, fruit, bread/cereal, milk/dairy products, eggs, and meat) during
      pregnancy was collected by a food frequency questionnaire. Women who indicated
      that they sometimes, often, or mostly consumed organic foods in at least one of
      the six food groups were classified as organic food consumers in analyses.
      Hypospadias and cryptorchidism diagnoses were retrieved from the Medical Birth
      Registry of Norway. We estimated odds ratios (ORs) and 95% confidence intervals
      (CIs) using multiple logistic regression. RESULTS: Seventy-four male newborns
      were diagnosed with hypospadias (0.2%), and 151 with cryptorchidism (0.4%). Women
      who consumed any organic food during pregnancy were less likely to give birth to
      a boy with hypospadias (OR = 0.42; 95% CI: 0.25, 0.70, based on 21 exposed cases)
      than women who reported they never or seldom consumed organic food. Associations
      with specific organic foods were strongest for vegetable (OR = 0.36; 95% CI:
      0.15, 0.85; 10 exposed cases) and milk/dairy (OR = 0.43; 95% CI: 0.17, 1.07; 7
      exposed cases) consumption. No substantial association was observed for
      consumption of organic food and cryptorchidism. CONCLUSIONS: Consumption of
      organically produced foods during pregnancy was associated with a lower
      prevalence of hypospadias in our study population. These findings were based on
      small numbers of cases and require replication in other study populations.

PMID- 26307852
TI  - Impact of Melatonin Enrichment during Germination of Legumes on Bioactive
      Compounds and Antioxidant Activity.
AB  - This study assesses the impact of melatonin enriched watering on the germination
      of lentils (Lens culinaris L.) and kidney beans (Phaseolus vulgaris L.). The
      melatonin levels in lentil and bean sprouts measured by HPLC-MS/MS were more
      important than those found in other legumes and sprouts, being higher in lentil
      (1090 ng/g) than in kidney bean (529 ng/g) sprouts. This alternative germination
      promoted a significant increase of the development of radicles in comparison with
      the traditional germination. The decreases in the phenolic load were less
      accentuated than previously observed (lentil sprouts displayed 394 mg gallic acid
      equivalents (GAE)/100 g of dry weight (DW)), probably due to the protective
      effect of melatonin. The antioxidant capacity (oxygen radical absorbing capacity
      assay) increased in these sprouts, reaching 85 and 56 MUmol of Trolox
      equivalents/g DW in lentils and beans, respectively. Hence, the melatonin
      enriched foods exhibited potent free radical scavenger and antioxidant functions
      that may be used as a nutritional strategy to alleviate and prevent chronic and
      age-related diseases. 

PMID- 26307853
TI  - Structure-Directing Effect of Alkali Metal Cations in New Molybdenum Selenites,
      Na2Mo2O5(SeO3)2, K2Mo2O5(SeO3)2, and Rb2Mo3O7(SeO3)3.
AB  - Both single crystals and pure polycrystalline samples of three new quaternary
      alkali metal molybdenum selenites, Na2Mo2O5(SeO3)2, K2Mo2O5(SeO3)2, and
      Rb2Mo3O7(SeO3)3, have been synthesized through hydrothermal and solid-state
      reactions using A2CO3 (A = Na, K, and Rb), MoO3, and SeO2 as reagents. The
      frameworks of all three materials consist of both families of second-order Jahn
      Teller distortive cations, i.e., the d(0) cation (Mo(6+)) and the lone pair
      cation (Se(4+)). Although the extent of framework distortions and the resulting
      occupation sites of alkali metal cations are dissimilar, Na2Mo2O5(SeO3)2 and
      K2Mo2O5(SeO3)2 exhibit similar three-dimensional networks that are composed of
      highly asymmetric Mo2O11 dimers and SeO3 polyhedra. Rb2Mo3O7(SeO3)3 reveals a two
      dimensional structure that is built with Mo3O15 trimers and SeO3 intralayer
      linkers. Close structural examinations suggest that the structure-directing
      effect of alkali metal cations is significant in determining the framework
      distortions and the dimensions of the molybdenum selenites. UV-vis diffuse
      reflectance and infrared spectroscopy, thermogravimetric analyses, and ion
      exchange reactions are reported, as are out-of-center distortion and dipole
      moment calculations. 

PMID- 26307854
TI  - Mechanism-based therapy for neuropathic pain-a concept in danger?

PMID- 26307855
TI  - Must we reduce pain intensity to treat chronic pain?

PMID- 26307856
TI  - Changes in functional connectivity of pain modulatory systems in women with
      primary dysmenorrhea.
AB  - Menstrual pain is the most prevalent gynecological complaint, and is usually
      without organic cause (termed primary dysmenorrhea, PDM). The high comorbidity in
      the later life of PDM with many functional pain disorders (associated with
      central dysfunction of pain inhibition, eg, fibromyalgia) suggests possible
      maladaptive functionality of pain modulatory systems already occurred in young
      PDM women, making them vulnerable to functional pain disorders. Periaqueductal
      gray (PAG) matter functions as a critical hub in the neuraxis of pain modulatory
      systems; therefore, we investigated the functional connectivity of PAG in PDM.
      Forty-six PDM subjects and 49 controls received resting-state functional magnetic
      resonance imaging during menstruation and periovulatory phases. The PAG of PDM
      subjects exhibited adaptive/reactive hyperconnectivity with the sensorimotor
      cortex during painful menstruation, whereas it exhibited maladaptive
      hypoconnectivity with the dorsolateral prefrontal cortex and default mode network
      (involving the ventromedial prefrontal cortex, posterior cingulate cortex, or
      posterior parietal cortex) during menstruation or periovulatory phase. We propose
      that the maladaptive descending pain modulatory systems in PDM may underpin the
      central susceptibility to subsequent development of various functional disorders
      later in life. This hypothesis is corroborated by the growing body of evidence
      that hypoconnectivity between PAG and default mode network is a coterminal to
      many functional pain disorders. 

PMID- 26307857
TI  - Translation of random painful stimuli into numerical responses in fibromyalgia
      and perioperative patients.
AB  - Number-based assessment tools are used to evaluate pain perception in patients
      and determine the effect of pain management. The aim of this study was to
      determine the ability of chronic and acute pain patients to score their response
      to randomly applied noxious stimuli and assess the effect of opioid treatment.
      Thirty-seven healthy controls, 30 fibromyalgia patients, and 62 postoperative
      patients with acute pain received random heat pain (Hp) and electrical pain (Ep)
      stimuli. All subjects rated their pain on an 11-point numerical rating scale
      (NRS). The data were analyzed using a penalty score system, based on the
      assumption that stimuli of higher intensity are scored with a greater NRS, and
      stratified into cohorts corresponding to "good," "mediocre," and "poor" scoring.
      Healthy controls were well able to score pain with 73% (Hp) and 81% (Ep) of
      subjects classified into cohort "good." Fibromyalgia had a negative effect on
      scoring with 45% (Hp, P = 0.03 vs controls) and 67% (Ep) of patients in cohort
      "good." In controls, scoring deteriorated during opioid administration leaving
      just 40% (Hp, P = 0.015 vs baseline) and 70% (Ep) of subjects in the cohort
      "good." Similar observations were made in fibromyalgia patients (P = 0.02) but
      not in surgical patients with postoperative pain. Consistency to grade pain using
      an NRS is high in healthy volunteers but deteriorates in chronic pain and during
      opioid administration to volunteers and chronic pain patients but not to acute
      pain patients. 

PMID- 26307858
TI  - Increasing placebo responses over time in U.S. clinical trials of neuropathic
      pain.
AB  - Recent failures of clinical trials of novel analgesics designed to treat
      neuropathic pain have led to much speculation about the underlying reasons. One
      often discussed possibility is that the placebo response in these trials has
      increased in recent years, leading to lower separation between the drug and
      placebo arms. Whether this has indeed occurred has not yet been adequately
      addressed. Here, we extracted data from published randomized controlled trials
      (RCTs) of drugs for the treatment of chronic neuropathic pain over the years 1990
      to 2013. We find that placebo responses have increased considerably over this
      period, but drug responses have remained stable, leading to diminished treatment
      advantage. This trend has been driven by studies conducted in the United States.
      Consideration of participant and study characteristics revealed that in the
      United States but not elsewhere, RCTs have increased in study size and length.
      These changes are associated with larger placebo response. Analysis of individual
      RCT time courses showed different kinetics for the treatment vs placebo
      responses, with the former evolving more quickly than the latter and plateauing,
      such that maximum treatment advantage was achieved within 4 weeks. 

PMID- 26307859
TI  - Pain and motor processing in the human cerebellum.
AB  - Pain-related adaptations in movement require a network architecture that allows
      for integration across pain and motor circuits. Previous studies addressing this
      issue have focused on cortical areas such as the midcingulate cortex. Here, we
      focus on pain and motor processing in the human cerebellum. The goal of this
      study was to identify areas of activation in the cerebellum, which are common to
      pain and motor processing, and to determine whether the activation is limited to
      the superior and inferior cerebellar motor maps or extends into multimodal areas
      of the posterior cerebellum. Our observations identified overlapping activity in
      left and right lobules VI and VIIb during pain and motor processing. Activation
      in these multimodal regions persisted when pain and motor processes were combined
      within the same trial, and activation in contralateral left lobule VIIb persisted
      when stimulation was controlled for. Functional connectivity analyses revealed
      significant correlations in the BOLD time series between multimodal cerebellar
      regions and sensorimotor regions in the cerebrum including anterior midcingulate
      cortex, supplementary motor area, and thalamus. The current findings are the
      first to show multimodal processing in lobules VI and VIIb for motor control and
      pain processing and suggest that the posterior cerebellum may be important in
      understanding pain-related adaptations in motor control. 

PMID- 26307860
TI  - Spinal translocator protein alleviates chronic neuropathic pain behavior and
      modulates spinal astrocyte-neuronal function in rats with L5 spinal nerve
      ligation model.
AB  - Recent studies reported the translocator protein (TSPO) to play critical roles in
      several kinds of neurological diseases including the inflammatory and neuropathic
      pain. However, the precise mechanism remains unclear. This study was undertaken
      to explore the distribution and possible mechanism of spinal TSPO against chronic
      neuropathic pain (CNP) in a rat model of L5 spinal nerve ligation (SNL). Our
      results showed that TSPO was upregulated in a time-related manner in the spinal
      dorsal horn after SNL. Spinal TSPO was predominately expressed in astrocytes. A
      single intrathecal injection of TSPO agonist Ro5-4864, but not TSPO antagonist
      PK11195, alleviated the mechanical allodynia in a dose-dependent manner. A single
      intraspinal injection of TSPO overexpression lentivirus (LV-TSPO), but not TSPO
      inhibited lentivirus (LV-shTSPO), also relieved the development of CNP.
      Intrathecal administration of 2 MUg Ro5-4864 on day 3 induced a significant
      increase of TSPO protein content at the early stage (days 5-7) while inhibited
      the TSPO activation during the chronic period (days 14-21) compared with the
      control group. Ro5-4864 suppressed the astrocytes and p-JNK1 activation and
      decreased the CXCL1 expression in both in vivo and in vitro studies. Ro5-4864
      also attenuated the spinal CXCR2 and p-ERK expressions. These results suggested
      that early upregulation of TSPO could elicit potent analgesic effects against
      CNP, which might be partly attributed to the inhibition of CXCL1-CXCR2-dependent
      astrocyte-to-neuron signaling and central sensitization. TSPO signaling pathway
      may present a novel strategy for the treatment of CNP. 

PMID- 26307861
TI  - Somatosensory assessment and conditioned pain modulation in temporomandibular
      disorders pain patients.
AB  - The pathophysiology and underlying pain mechanisms of temporomandibular disorders
      (TMD) are poorly understood. The aims were to assess somatosensory function at
      the temporomandibular joints (TMJs) and to examine whether conditioned pain
      modulation (CPM) differs between TMD pain patients (n = 34) and healthy controls
      (n = 34). Quantitative sensory testing was used to assess the somatosensory
      function. Z-scores were calculated for patients based on reference data.
      Conditioned pain modulation was tested by comparing pressure pain thresholds
      (PPTs) before, during, and after the application of painful and nonpainful cold
      stimuli. Pressure pain thresholds were measured at the most painful TMJ and
      thenar muscle (control). Data were analyzed with analyses of variance. Most
      (85.3%) of the patients exhibited at least 1 or more somatosensory abnormalities
      at the most painful TMJ with somatosensory gain with regard to PPT and punctate
      mechanical pain stimuli, and somatosensory loss with regard to mechanical
      detection and vibration detection stimuli as the most frequent abnormalities.
      There was a significant CPM effect (increased PPT) at both test sites during
      painful cold application in healthy controls and patients (P < 0.001). There was
      no significant difference in the relative CPM effect during painful cold
      application between groups (P = 0.227). In conclusion, somatosensory
      abnormalities were commonly detected in TMD pain patients and CPM effects were
      similar in TMD pain patients and healthy controls. 

PMID- 26307862
TI  - What is the meaning of "small fiber neuropathy" in fibromyalgia?

PMID- 26307863
TI  - The splenic injury outcomes trial: An American Association for the Surgery of
      Trauma multi-institutional study.
AB  - BACKGROUND: Delayed splenic hemorrhage after nonoperative management (NOM) of
      blunt splenic injury (BSI) is a feared complication, particularly in the
      outpatient setting. Significant resources, including angiography (ANGIO), are
      used in an effort to prevent delayed splenectomy (DS). No prospective, long-term
      data exist to determine the actual risk of splenectomy. The purposes of this
      trial were to ascertain the 180-day risk of splenectomy after 24 hours of NOM of
      BSI and to determine factors related to splenectomy. METHODS: Eleven Level I
      trauma centers participated in this prospective observational study. Adult
      patients achieving 24 hours of NOM of their BSI were eligible. Patients were
      followed up for 180 days. Demographic, physiologic, radiographic, injury-related
      information, and spleen-related interventions were recorded. Bivariate and
      multivariable analyses were used to determine factors associated with DS.
      RESULTS: A total of 383 patients were enrolled. Twelve patients (3.1%) underwent
      in-hospital splenectomy between 24 hours and 9 days after injury. Of 366
      discharged with a spleen, 1 (0.27%) required readmission for DS on postinjury Day
      12. No Grade I injuries experienced DS. The splenectomy rate after 24 hours of
      NOM was 1.5 per 1,000 patient-days. Only extravasation from the spleen at time of
      admission (ADMIT-BLUSH) was associated with splenectomy (odds ratio, 3.6; 95%
      confidence interval, 1.4-12.4). Of patients with ADMIT-BLUSH (n = 49), 17 (34.7%)
      did not have ANGIO with embolization (EMBO), and 2 of those (11.8%) underwent
      splenectomy; 32 (65.3%) underwent ANGIO with EMBO, and 2 of those (6.3%, p =
      0.6020 compared with no ANGIO with EMBO) required splenectomy. CONCLUSION:
      Splenectomy after 24 hours of NOM is rare. After the initial 24 hours, no
      additional interventions are warranted for patients with Grade I injuries. For
      Grades II to V, close observation as an inpatient or outpatient is indicated for
      10 days to 14 days. ADMIT-BLUSH is a strong predictor of DS and should lead to
      close observation or earlier surgical intervention. LEVEL OF EVIDENCE:
      Prognostic/epidemiological study, level III; therapeutic study, level IV.

PMID- 26307864
TI  - The evil of good is better: Making the case for basic life support transport for
      penetrating trauma victims in an urban environment.
AB  - BACKGROUND: Controversy remains over the ideal way to transport penetrating
      trauma victims in an urban environment. Both advance life support (ALS) and basic
      life support (BLS) transports are used in most urban centers. METHODS: A
      retrospective cohort study was conducted at an urban Level I trauma center.
      Victims of penetrating trauma transported by ALS, BLS, or police from January 1,
      2008, to November 31, 2013, were identified. Patient survival by mode of
      transport and by level of care received was analyzed using logistic regression.
      RESULTS: During the study period, 1,490 penetrating trauma patients were
      transported by ALS (44.8%), BLS (15.6%), or police (39.6%) personnel. The
      majority of injuries were gunshot wounds (72.9% for ALS, 66.8% for BLS, 90% for
      police). Median transport minutes were significantly longer for ALS (16 minutes)
      than for BLS (14.5 minutes) transports (p = 0.012). After adjusting for transport
      time and Injury Severity Score (ISS), among victims with an ISS of 0 to 30, there
      was a 2.4-fold increased odds of death (95% confidence interval [CI], 1.3-4.4) if
      transported by ALS as compared with BLS. With an ISS of greater than 30, this
      relationship did not exist (odds ratio, 0.9; 95% CI, 0.3-2.7). When examined by
      type of care provided, patients with an ISS of 0 to 30 given ALS support were 3.7
      times more likely to die than those who received BLS support (95% CI, 2.0-6.8).
      Among those with an ISS of greater than 30, no relationship was evident (odds
      ratio, 0.9; 95% CI, 0.3-2.7). CONCLUSION: Among penetrating trauma victims with
      an ISS of 30 or lower, an increased odds of death was identified for those
      treated and/or transported by ALS personnel. For those with an ISS of greater
      than 30, no survival advantage was identified with ALS transport or care. Results
      suggest that rapid transport may be more important than increased interventions.
      LEVEL OF EVIDENCE: Therapeutic study, level IV.

PMID- 26307865
TI  - Mortality after emergency surgery continues to rise after discharge in the
      elderly: Predictors of 1-year mortality.
AB  - BACKGROUND: It is known that emergency surgery in the elderly is associated with
      high short-term mortality, but longer-term outcomes are not well described. We
      hypothesized that 30-day mortality may underestimate the true operative mortality
      experienced in this cohort. The purposes of this study were to characterize
      postoperative mortality rates extending to 1 year and to identify preoperative
      predictors of 1 year mortality after emergency abdominal surgery. METHODS: We
      retrospectively reviewed the records of all patients older than 70 years who
      underwent emergency abdominal surgery at a major teaching hospital between 2006
      and 2011. Demographics, preoperative physiology, prehospital status, body mass
      index, laboratory values, Charlson scores, comorbid conditions, American Society
      of Anesthesiologists classification, and operative details were recorded. The
      primary end point was 1-year mortality. Complementary log-log binary regression
      was used to determine independent predictors of death. Model discrimination was
      evaluated using the c statistic. RESULTS: A total of 390 patients met our
      inclusion criteria. The mean age was 79 years, and 56% were women. Postoperative
      mortality was 16.2% at 30 days and 32.5% at 1 year, reflecting a doubling of
      mortality over 11 months. Independent preoperative predictors of 1-year mortality
      were Charlson score of 4 or higher (hazard ratio [HR], 1.79; 95% confidence
      interval [CI], 1.38-2.34), American Society of Anesthesiologists class of 4 or
      higher (HR, 1.66; 95% CI, 1.22-2.21), albumin less than 3.5 (HR, 1.71; 95% CI,
      1.31-2.28), and body mass index lower than 18.5 (HR, 3.36; 95% CI, 1.48-6.86).
      The c statistic was 0.81. CONCLUSION: The 1-year mortality after emergency
      surgery in the elderly is significantly higher than that at 30 days. We
      identified a constellation of preoperative clinical markers that were highly
      predictive of this poor late outcome. The presence of these findings in the
      emergency setting should prompt preoperative discussion about treatment goals and
      encourage surgeons to set realistic expectations about outcomes with the patient
      and family. Future studies will develop a clinical scoring tool that can be
      applied at the bedside to provide more effective counseling for this high-risk
      population. LEVEL OF EVIDENCE: Epidemiologic/prognostic study, level III;
      therapeutic study, level IV.

PMID- 26307866
TI  - Variability in interhospital trauma data coding and scoring: A challenge to the
      accuracy of aggregated trauma registries.
AB  - BACKGROUND: Analyses of data aggregated in state and national trauma registries
      provide the platform for clinical, research, development, and quality improvement
      efforts in trauma systems. However, the interhospital variability and accuracy in
      data abstraction and coding have not yet been directly evaluated. METHODS: This
      multi-institutional, Web-based, anonymous study examines interhospital
      variability and accuracy in data coding and scoring by registrars. Eighty-two
      American College of Surgeons (ACS)/state-verified Level I and II trauma centers
      were invited to determine different data elements including diagnostic,
      procedure, and Abbreviated Injury Scale (AIS) coding as well as selected National
      Trauma Data Bank definitions for the same fictitious case. Variability and
      accuracy in data entries were assessed by the maximal percent agreement among the
      registrars for the tested data elements, and 95% confidence intervals were
      computed to compare this level of agreement to the ideal value of 100%.
      Variability and accuracy in all elements were compared (chi testing) based on
      Trauma Quality Improvement Program (TQIP) membership, level of trauma center, ACS
      verification, and registrar's certifications. RESULTS: Fifty registrars (61%)
      completed the survey. The overall accuracy for all tested elements was 64%.
      Variability was noted in all examined parameters except for the place of
      occurrence code in all groups and the lower extremity AIS code in Level II trauma
      centers and in the Certified Specialist in Trauma Registry- and Certified
      Abbreviated Injury Scale Specialist-certified registrar groups. No differences in
      variability were noted when groups were compared based on TQIP membership, level
      of center, ACS verification, and registrar's certifications, except for
      prehospital Glasgow Coma Scale (GCS), where TQIP respondents agreed more than non
      TQIP centers (p = 0.004). CONCLUSION: There is variability and inaccuracy in
      interhospital data coding and scoring of injury information. This finding casts
      doubt on the validity of registry data used in all aspects of trauma care and
      injury surveillance.

PMID- 26307867
TI  - Does proximity to violence negatively influence attitudes toward exception from
      informed consent in emergency research?
AB  - BACKGROUND: Trauma research has been limited by perceived patient reluctance to
      participate in exception from informed consent (EFIC) studies. We hypothesized
      that race, socioeconomic status, and proximity to violence influence willingness
      to participate in and perception of EFIC research among at-risk populations.
      METHODS: Trauma patients, families, and community members ranked statements
      regarding attitude toward EFIC in the context of an upcoming trial and
      willingness to participate in emergency research using a 5-point Likert scale
      during a community consultation. Higher total scores reflected a more positive
      attitude regarding EFIC (range, 6-30; neutral, 18) and willingness (range, 23
      115; neutral, 69). Subject zip code was used to calculate median income, as an
      estimate for socioeconomic status, and proximity to the five most violent city
      zip codes. Linear regression, Spearman's correlation, and Kruskal-Wallis tests (p
      < 0.05) were used to evaluate relationships between estimated socioeconomic
      status, race, mechanism of injury, proximity to violence, and attitudes toward
      EFIC. RESULTS: A total of 179 subjects participated including trauma patients (n
      = 99), families (n = 33), and community members (n = 47). Overall, participants
      were supportive of EFIC and reported high scores in willingness to participate
      (median, 24; interquartile range, 21-25; median 89, interquartile range, 82-95,
      respectively). Proximity to violence did correlate with race (p = 0.03) but was
      not associated with violent mechanism of injury, perception of EFIC, or
      willingness to participate in emergency research. Estimated socioeconomic status
      and race did not correlate with perception of or willingness to participate in
      EFIC. CONCLUSION: Based on our data, there is no correlation between either
      proximity to violence or estimated socioeconomic status and willingness to
      participate in EFIC research. Given this lack of correlation, researchers should
      partner with at-risk communities to conduct EFIC studies without concern for
      limited participation. LEVEL OF EVIDENCE: Epidemiologic/prognostic study, level
      III.

PMID- 26307868
TI  - Functional and long-term outcomes in severe traumatic brain injury following
      regionalization of a trauma system.
AB  - BACKGROUND: We previously demonstrated that regionalization of trauma (RT)
      significantly reduced in-hospital mortality from 19% to 14% in patients with
      severe traumatic brain injury (sTBI). However, functional and long-term outcomes
      had not been assessed. We hypothesized that RT would be associated with improved
      functional and long-term outcomes in sTBI patients. METHODS: All TBI patients
      older than 14 years with a head Abbreviated Injury Scale (AIS) score of 3 or
      greater were identified from the RT database and matched to the state death index
      and the regional TBI rehabilitation (TBIr) database. Data from 2008 through 2012
      were analyzed before and after RT in 2010. For patients discharged to the TBIr
      unit, overall Functional Independence Measure (FIM) scores and FIM score gains
      were compared before and after RT. RESULTS: A total of 3,496 patients with sTBI
      were identified in the RT database, 1,359 in the pre-RT and 2,137 in the post-RT
      period. The mortality rate after discharge decreased significantly after RT from
      21% to 16% (p < 0.0001) at 30 days and from 24% to 20% (p = 0.004) at 6 months.
      Multivariable logistic regression demonstrated RT to be an independent predictor
      against mortality at 30 days (odds ratio, 0.74; 95% confidence interval, 0.60
      0.91; C statistic, 0.84) and 6 months (odds ratio, 0.82; 95% confidence interval,
      0.67-0.99; C statistic, 0.82). Discharges to the TBIr unit increased from 117
      (9%) in the pre-RT to 297 (14%) in the post-RT period (p < 0.0001), while
      discharges to home and non-TBIr units remained similar. Injury Severity Score
      (ISS) and Glasgow Coma Scale (GCS) score for all discharged patients remained
      similar. FIM admission scores were similar in the pre-RT (median, 54;
      interquartile range [IQR], 30-65) and post-RT period (median, 48; IQR, 31-61) (p
      = 0.2) and remained similar at discharge in the pre-RT (median, 92; IQR, 75-102)
      and post-RT period (median, 89; IQR, 73-100) (p = 0.1). TBIr patients showed
      similar FIM score gains in the pre-RT (median, 37; IQR, 26-46) and post-RT period
      (median, 36; IQR, 24-49) (p = 0.6). CONCLUSION: RT was associated with reduced
      long-term mortality, increased TBIr admissions, and similar FIM score
      improvements for patients with sTBI. LEVEL OF EVIDENCE: Therapeutic/care
      management study, level IV.

PMID- 26307869
TI  - Factors associated with patients transferred from undesignated trauma centers to
      trauma centers.
AB  - BACKGROUND: Timely access to the appropriate level of care, both in the
      prehospital and in the hospital setting, is necessary to optimize outcomes in
      severely injured pediatric trauma patients. However, a substantial portion of the
      pediatric population does not have adequate timely access to a verified Level 1
      trauma center. This study aimed to identify significant predictors of in-hospital
      mortality and transfer to a higher level of care. This is the first statewide
      analysis that includes pediatric patients who are first seen at nontrauma centers
      (NTCs). METHODS: Mortality interhospital transfers to a higher level of care were
      analyzed for the first hospital of care. Clustering was accounted for by
      generalized estimating equations. p < 0.01 was considered significant. RESULTS:
      Younger age was significantly associated with mortality for all patients and with
      transfer for less severely injured children (Injury Severity Score [ISS] < 15).
      The odds of mortality in NTCs were lower than in Level 1 trauma centers; however,
      the majority of NTC patients were transferred, artificially decreasing NTC
      mortality. The type of trauma (blunt or penetrating) was significantly associated
      with both mortality and transfer for more severe cases. Although insurance was
      not significantly associated with transfer, self-pay patients had significantly
      higher mortality odds. CONCLUSION: The NTCs are transferring 98% of their
      patients, even those with very low ISS and high Glasgow Coma Scale (GCS). Further
      evaluation of the outcomes and characteristics of patients transferred from NTCs
      will provide important information to inform the triage guidelines to potentially
      safely avoid transfer of less severely injured patients from NTCs in their
      community. LEVEL OF EVIDENCE: Therapeutic study, level IV;
      epidemiologic/prognostic study, level III.

PMID- 26307870
TI  - Bowel obstructions and incisional hernias following trauma laparotomy and the
      nonoperative therapy of solid organ injuries: A retrospective population-based
      analysis.
AB  - BACKGROUND: Small bowel obstruction (SBO) and incisional hernia (IH) represent
      the most common long-term complications of laparotomy. They may also be more
      common among injured patients than for elective/nontrauma emergency scenarios.
      Unfortunately, the population-based incidence of SBO and IH following trauma
      laparotomy is unknown. The aim of this study was to define the long-term,
      population-based incidence of SBO and IH following both trauma laparotomy as well
      as the nonoperative therapy of solid organ injuries. METHODS: All injured
      patients admitted to a Level 1 trauma center (2002-2013) who underwent (1) a
      laparotomy or nonoperative care of (2) splenic and/or (3) hepatic injuries were
      linked with the Alberta Health Services Discharge Database to identify all
      readmissions for subsequent SBO and/or IH within the province. Standard
      statistical methodology was used (p < 0.05). RESULTS: Of 484 patients who
      underwent a trauma laparotomy, 29 (6%) and 42 (9%) required readmission for SBO
      and IH, respectively (0.13 SBO and 0.10 IH admissions per patient year). Patients
      who underwent nonoperative management of their liver and/or spleen injuries
      displayed long-term SBO rates of 1% (6 of 619) and 0.7% (4 of 606), respectively.
      The rate of SBO and IH in patients with unnecessary laparotomies was equivalent
      to therapeutic procedures (p = 0.183). Topical hemostatic agents, repeat
      laparotomies, and injury pattern did not alter SBO or IH rates (p > 0.05).
      CONCLUSION: The population-based, long-term rate of clinically relevant SBO and
      IH following trauma laparotomies is 15%. This increases to 19% on a per-admission
      basis. Nontherapeutic scenarios, injury pattern, topical hemostatics, and open
      abdomens did not alter complication rates. LEVEL OF EVIDENCE: Therapeutic study,
      level IV.

PMID- 26307871
TI  - A multi-institution prospective observational study of small bowel obstruction:
      Clinical and computerized tomography predictors of which patients may require
      early surgery.
AB  - BACKGROUND: For patients with adhesive small bowel obstruction (ASBO), early
      surgery after a failed trial of nonoperative treatment can improve outcome.
      However, deciding which patients require early surgery is difficult, given the
      lack of specific clinical or radiographic signs. The study goals were to identify
      clinical and computed tomography (CT) predictors of which patients may need early
      surgery and to evaluate the utility of the common CT findings. METHODS: This was
      a multi-institution prospective observational study for patients who were
      admitted with ASBO. Patients were excluded if their SBO were not managed
      conservative initially; were within 30 days postoperatively; were caused by
      external hernias, small bowel tumor, or intussusception; and were related to
      Crohn's disease. Clinical and laboratory variables were collected prospectively.
      CT findings were interpreted by a blinded designated radiologist. To identify
      significant predictors, we performed a multivariable regression analysis.
      RESULTS: During 22 months, we enrolled 200 patients with ASBO. Patients' mean
      (SD) age was 60 (18) years; 50% were male. Fifty-two patients (26%) underwent
      surgery. Of those who underwent surgery, the median duration of nonoperative
      treatment was 1.5 days (interquartile range, 1-2.5 days). In the regression
      model, we identified no flatus (odds ratio [OR], 3.28; 95% confidence interval
      [CI], 1.51-7.12; p = 0.003), presence of free fluid on CT (OR, 2.59; 95% CI, 1.13
      5.90; p = 0.023), and high-grade obstruction by CT (OR, 2.44; 95% CI, 1.10-5.43;
      p = 0.028) to be significant predictors for ASBO patients who may need early
      surgery. CONCLUSION: In this study, we prospectively derived one clinical and two
      CT predictors which ASBO patients may benefit from an early surgical
      intervention. However, a future study to validate these predictors is needed.
      LEVEL OF EVIDENCE: Therapeutic study, level III; prognostic study, level II.

PMID- 26307873
TI  - Acute kidney injury following severe trauma: Risk factors and long-term outcome.
AB  - BACKGROUND: The trauma patient sustains numerous potentially harmful insults that
      may contribute to a notable risk of acute kidney injury (AKI). The aim of this
      study was to investigate the incidence of and to identify risk factors for AKI in
      severely injured trauma patients admitted to the intensive care unit (ICU). The
      patients were followed up for 1 year with respect to survival and end-stage renal
      disease. METHODS: Trauma patients admitted to the ICU for more than 24 hours at a
      Level I trauma center were included. The outcome measure was AKI diagnosed Days 2
      to 7 of ICU treatment. Regression analysis was performed to identify factors
      associated with AKI development. RESULTS: A quarter of the patients (103 of 413)
      developed AKI within the first week of ICU admission. AKI was associated with
      increased 30-day (17.5% vs. 5.8%) and 1-year (26.2% vs. 7.1%) mortality. Risk
      factors for AKI were male sex, age, nondiabetic comorbidity, diabetes mellitus,
      Injury Severity Score (ISS) greater than 40, massive transfusion, and volume
      loading with hydroxyethyl starch (HES) within the first 24 hours. Unexpectedly,
      sepsis before AKI onset, admission hypotension, and extensive contrast loading
      (>150 mL) were not associated with AKI development. None of the surviving AKI
      patients had developed end-stage renal disease 1 year after injury. CONCLUSION:
      AKI in ICU-admitted trauma patients is a common complication with substantial
      mortality. Diabetes, male sex, and severe injury were strong risk factors, but
      age, nondiabetic comorbidity, massive transfusion, and resuscitation with HES
      were also associated with postinjury AKI. Based on the results of the current
      study, volume resuscitation with HES cannot be recommended in trauma patients.
      LEVEL OF EVIDENCE: Prognostic study, level III; therapeutic study, level IV.

PMID- 26307872
TI  - Outcomes after emergency abdominal surgery in patients with advanced cancer:
      Opportunities to reduce complications and improve palliative care.
AB  - BACKGROUND: There is increasing emphasis on the appropriateness and quality of
      acute surgical care for patients with serious illness and at the end of life.
      However, there is a lack of evidence regarding outcomes after emergent major
      abdominal surgery among patients with advanced cancer to guide treatment
      decisions. This analysis sought to characterize adverse outcomes (mortality,
      complications, institutional discharge) and to identify factors independently
      associated with 30-day mortality among patients with disseminated cancer who
      undergo emergent abdominal surgery for intestinal obstruction or perforation.
      METHODS: This is a retrospective cohort study of 875 disseminated cancer patients
      undergoing emergency surgery for perforation (n = 499) or obstruction (n = 376)
      at hospitals participating in the American College of Surgeons' National Surgical
      Quality Improvement Program from 2005 to 2012. Predictors of 30-day mortality
      were identified using multivariate logistic regression. RESULTS: Among patients
      who underwent surgery for perforation, 30-day mortality was 34%, 67% had
      complications, and 52% were discharged to an institution. Renal failure, septic
      shock, ascites, dyspnea at rest, and dependent functional status were independent
      preoperative predictors of death at 30 days. When complications were considered,
      postoperative respiratory complications and age (75-84 years) were also
      predictors of mortality.Patients who had surgery for obstruction had a 30-day
      mortality rate of 18% (n = 68), 41% had complications, and 60% were discharged to
      an institution. Dependent functional status and ascites were independent
      predictors of death at 30 days. In addition to these predictors, postoperative
      predictors of mortality included respiratory and cardiac complications. Few
      patients (4%) had do-not-resuscitate orders before surgery. CONCLUSION: Emergency
      abdominal operations in patients with disseminated cancer are highly morbid, and
      many patients die soon after surgery. High rates of complications and low rates
      of preexisting do-not-resuscitate orders highlight the need for targeted
      interventions to reduce complications and integrate palliative approaches into
      the care of these patients. LEVEL OF EVIDENCE: Prognostic study, level III;
      therapeutic study, level IV.

PMID- 26307874
TI  - Vital capacity helps predict pulmonary complications after rib fractures.
AB  - BACKGROUND: Traumatic rib fractures are associated with significant morbidity.
      Vital capacity (VC) assesses pulmonary function; however, limited data link VC to
      patient outcomes. Our objective was to determine if VC predicted complications
      and disposition in patients with rib fractures. METHODS: This is a retrospective
      chart review of all patients with fractured ribs admitted to a Level 1 trauma
      center during a 4-year period. Patients were excluded if no VC was performed
      within 48 hours of admission. Data collected included demographics,
      hospital/intensive care unit length of stay, epidural, discharge to home versus
      extended care facility, mortality, chest Abbreviated Injury Scale (AIS) score,
      Injury Severity Score (ISS), number of rib fractures, hemothorax/pneumothorax,
      presence of pulmonary contusion, presence of chest tube, chronic obstructive
      pulmonary disease, and average daily VC (percentage of predicted). Pulmonary
      complication was defined as pneumonia, need for intubation, new home O2
      requirement, readmission for pulmonary issue, or intensive care unit transfer.
      Statistical analysis was performed using chi and multivariate logistic
      regression. RESULTS: Of 801 patients with rib fractures, 683 had VC performed
      within 48 hours. Average age was 53 years, median ISS was 13 (interquartile
      range, 9-18), and median length of stay was 5 days. Most (72%) were discharged
      home, and 26% went to extended care facility. Ten percent developed a pulmonary
      complication, and there were nine deaths. Every 10% increase in VC was associated
      with 36% decrease in likelihood of pulmonary complication. Patients with a VC
      greater than 50% had a significantly lower association of pulmonary complication
      (p = 0.017), and a VC of less than 30% was independently associated with
      pulmonary complication (odds ratio, 2.36). CONCLUSION: Patients with fractured
      ribs and VC of less than 30% have significant association for pulmonary
      complication. Higher VC is associated with lower likelihood of pulmonary
      complication. VC may help identify those at risk for complications after rib
      fractures, but a prospective study is necessary to confirm these findings. LEVEL
      OF EVIDENCE: Prognostic/epidemiologic study, level IV.

PMID- 26307876
TI  - Traumatic pulmonary pseudocysts after blunt chest trauma: Prevalence, mechanisms
      of injury, and computed tomography findings.
AB  - BACKGROUND: Traumatic pulmonary pseudocyst (TPP) is a rare complication of blunt
      chest trauma and closely related with severe injury. However, it has been poorly
      documented. We present a retrospective review of TPP cases treated at our
      hospital. METHODS: The medical records and chest computed tomography scans of
      patients with TPP treated from January 2010 to December 2013 were retrospectively
      studied. RESULTS: A total of 978 patients underwent chest computed tomography for
      blunt chest trauma during the study period, and 81 (8.3%) had a total of 150
      TPPs. The most common mechanism of injury was being struck by a motorized vehicle
      (n = 25, 30.9%). The mean (SD) Injury Severity Score (ISS) of the 81 patients was
      33.2 (11.4). The prevalence of TPP was higher in younger patients (p = 0.011),
      but the total number of fractured ribs was significantly lower (p = 0.001). In a
      subgroup analysis performed according to pseudocyst location, the
      intraparenchymal group had more severe injuries than the subpleural group (ISS,
      23.3 vs. 32.4, p < 0.001; chest Abbreviated Injury Scale [AIS] score, 3.4 vs.
      4.0, p < 0.001; number of associated injuries, 2.9 vs. 4.0, p = 0.001). By
      multivariate analysis, ISS, age, and number of associated injuries were
      significantly different in these two groups (p = 0.038, p = 0.006, and p = 0.045,
      respectively). CONCLUSION: The prevalence of TPP among cases of blunt chest
      trauma was 8.3% and was higher in those struck by a vehicle and younger patients.
      Intraparenchymal pseudocyst was found to be related to more severe injuries. TPP
      was a self-limiting condition that does not require specific treatment. LEVEL OF
      EVIDENCE: Prognostic/epidemiologic study, level IV.

PMID- 26307875
TI  - Misclassification of acute respiratory distress syndrome after traumatic injury:
      The cost of less rigorous approaches.
AB  - BACKGROUND: Adherence to rigorous research protocols for identifying adult
      respiratory distress syndrome (ARDS) after trauma is variable. To examine how
      misclassification of ARDS may bias observational studies in trauma populations,
      we evaluated the agreement of two methods for adjudicating ARDS after trauma: the
      current gold standard, direct review of chest radiographs and review of dictated
      radiology reports, a commonly used alternative. METHODS: This nested cohort study
      included 123 mechanically ventilated patients between 2005 and 2008, with at
      least one PaO2/FIO2 less than 300 within the first 8 days of admission. Two
      blinded physician investigators adjudicated ARDS by two methods. The
      investigators directly reviewed all chest radiographs to evaluate for bilateral
      infiltrates. Several months later, blinded to their previous assessments, they
      adjudicated ARDS using a standardized rubric to classify radiology reports. A
      kappa statistics was calculated. Regression analyses quantified the association
      between established risk factors as well as important clinical outcomes and ARDS
      determined by the aforementioned methods as well as hypoxemia as a surrogate
      marker. RESULTS: The kappa was 0.47 for the observed agreement between ARDS
      adjudicated by direct review of chest radiographs and ARDS adjudicated by review
      of radiology reports. Both the magnitude and direction of bias on the estimates
      of association between ARDS and established risk factors as well as clinical
      outcomes varied by method of adjudication. CONCLUSION: Classification of ARDS by
      review of dictated radiology reports had only moderate agreement with the current
      gold standard, ARDS adjudicated by direct review of chest radiographs. While the
      misclassification of ARDS had varied effects on the estimates of associations
      with established risk factors, it tended to weaken the association of ARDS with
      important clinical outcomes. A standardized approach to ARDS adjudication after
      trauma by direct review of chest radiographs will minimize misclassification bias
      in future observational studies. LEVEL OF EVIDENCE: Diagnostic study, level II.

PMID- 26307877
TI  - Elevations in inflammatory cytokines are associated with poor outcomes in
      mechanically ventilated burn patients.
AB  - BACKGROUND: The treatment of burn patients who undergo mechanical ventilation is
      complicated by many factors; patient outcomes and mortality could potentially be
      improved with predictive biomarkers. Severe burn provokes a systemic inflammatory
      response characterized by the release of a host of cytokines. Recent studies
      evaluated the prognostic value of temporal changes in cytokine levels in several
      patient populations, but few have compared differences in the cytokine profiles
      of survivors and nonsurvivors following severe burn. We previously compared high
      frequency percussive ventilation and low-tidal-volume ventilation and found no
      difference in mortality or cytokine levels between the two treatments. Since it
      is unknown whether cytokine levels are predictive of mortality in these patients,
      we performed a post hoc analysis comparing cytokine levels in survivors and
      nonsurvivors. METHODS: We evaluated plasma levels of several cytokines
      (interleukin 1beta [IL-1beta], IL-6, IL-8, granulocyte-macrophage colony
      stimulating factor, and tumor necrosis factor alpha) for their prognostic
      biomarker potential related to mortality at 0, 3, and 7 days in survivors and
      nonsurvivors of burns. RESULTS: While the majority of values for IL-1beta,
      granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor alpha
      fell below the limit of quantification, univariate analysis demonstrated higher
      plasma levels of IL-6 and IL-8 in nonsurvivors on Day 7. Logistic regression
      revealed that elevated plasma IL-8 was independently associated with an increased
      likelihood of the composite end point of death or ventilator-associated pneumonia
      with odds ratios of 7.9, 26, and 7.3 on Days 0, 3, and 7, respectively.
      CONCLUSION: Early increases in plasma IL-8 are associated with a multifold
      increase in death or ventilator-associated pneumonia in mechanically ventilated
      burn patients. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level IV;
      therapeutic study, level IV.

PMID- 26307878
TI  - Leukopenia is associated with worse but not prohibitive outcomes following
      emergent abdominal surgery.
AB  - BACKGROUND: There are little data currently available to guide surgical decision
      making regarding emergent surgical interventions in leukopenic patients. The
      purpose of this study was to investigate the impact of leukopenia among patients
      undergoing emergency abdominal operations to better guide preoperative decision
      making. METHODS: The 2005 to 2012 American College of Surgeons' National Surgical
      Quality Improvement Program database was queried to identify patients who
      underwent emergent laparotomy. Patients were stratified by preoperative white
      blood cell (WBC) count (<4.0 * 10(9)/L vs. 4.0-12.0 * 10(9)/L). Baseline
      demographics, comorbidities, and outcomes were compared. Multivariable logistic
      regression was performed to estimate the adjusted association between leukopenia
      and mortality, taking into account the robust array of patient-related factors.
      RESULTS: Of the 20,443 patients who met study criteria, 2,057 (8.2%) were
      leukopenic (WBC < 4.0) before surgery. Unadjusted comparison demonstrated
      significantly increased major morbidity (45.4% vs. 26.9%, p < 0.001) as well as
      mortality (24.4% vs. 10.8%, p < 0.001) for patients with leukopenia compared with
      patients with a normal preoperative WBC count. Only 46.0% (n = 947) of patients
      with leukopenia before surgery were able to avoid major morbidity or mortality
      compared with 69.4% (n = 15,974) of patients with a normal preoperative WBC count
      (p < 0.001). After multivariable adjustment for patient-related factors,
      leukopenia was maintained as a significant predictor of mortality. CONCLUSION:
      Although leukopenia remains associated with mortality in patients undergoing
      emergent laparotomy despite adjustment for other patient-related factors, it is
      not necessarily prohibitive. Understanding the risk of complications and
      mortality associated with these procedures is pertinent for preoperative clinical
      decision making. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level
      III.

PMID- 26307879
TI  - The financial burden of emergency general surgery: National estimates 2010 to
      2060.
AB  - BACKGROUND: Adoption of the acute care surgery model has led to increasing
      volumes of emergency general surgery (EGS) patients at trauma centers. However,
      the financial burden of EGS services on trauma centers is unknown. This study
      estimates the current and future costs associated with EGS hospitalization
      nationwide. METHODS: We applied the American Association for the Surgery of
      Trauma's DRG International Classification of Diseases-9th Rev. criteria for
      defining EGS to the 2010 National Inpatient Sample (NIS) data and identified
      adult EGS patients. Cost of hospitalization was obtained by converting reported
      charges to cost using the 2010 all-payer inpatient cost-to-charge ratio for all
      hospitals in the NIS database. Cost was modeled via a log-gamma model in a
      generalized linear mixed model to account for potential correlation in cost
      within states and hospitals in the NIS database. Patients' characteristics and
      hospital factors were included in the model as fixed effects, while state and
      hospital were included as random effects. The national incidence of EGS was
      calculated from NIS data, and the US Census Bureau population projections were
      used to estimate incidence for 2010 to 2060. Nationwide costs were obtained by
      multiplying projected incidences by estimated costs and reported in year 2010 US
      dollar value. RESULTS: Nationwide, there were 2,640,725 adult EGS
      hospitalizations in 2010. The national average adjusted cost per EGS
      hospitalization was $10,744 (95% confidence interval [CI], $10,615-$10,874);
      applying these cost data to the national EGS hospitalizations gave a total
      estimated cost of $28.37 billion (95% CI, $28.03-$28.72 billion). Older age
      groups accounted for greater proportions of the cost ($8.03 billion for age >= 75
      years, compared with $1.08 billion for age 18-24 years). As the US population
      continues to both grow and age, EGS costs are projected to increase by 45% to
      $41.20 billion (95% CI, $40.70-$41.7 billion) by 2060. CONCLUSION: EGS
      constitutes a significant portion of US health care costs and is expected to rise
      with the demographic changes in the population. Trauma centers should conduct
      careful financial analyses of their EGS services, based on their unique case mix
      and payer mix. LEVEL OF EVIDENCE: Economic analysis, level III.

PMID- 26307880
TI  - A new device for the prevention of pulmonary embolism in critically ill patients:
      Results of the European Angel Catheter Registry.
AB  - BACKGROUND: Pulmonary embolism (PE) is a potentially life-threatening
      complication of critical illness. In trauma and neurosurgical patients with
      contraindications to anticoagulation, inferior vena cava (IVC) filters have been
      used to prevent PE, but their associated long-term complication rates and
      difficulties associated with filter removal have limited their use. The Angel
      catheter is a temporary device, which combined an IVC filter with a triple-lumen
      central venous catheter (IVC filter-catheter) and is intended for bedside
      placement and removal when no longer indicated. METHODS: This study presents data
      from a European Registry of 60 critically ill patients in whom the IVC filter
      catheter was used to prevent PE. The patients were all at high risk of PE
      development or recurrence and had contraindications to anticoagulation. The
      primary end points of this study were to evaluate the safety (in particular, the
      presence of infectious or thrombotic events) and effectiveness (the numbers of
      PEs and averted PEs) of the IVC filter-catheter. RESULTS: The main diagnosis
      before catheter insertion was major trauma in 33 patients (55%), intracerebral
      hemorrhage or stroke in 9 (15%), a venous thromboembolic event in 9 (15%), and
      active bleeding in 6 (10%). The IVC filter-catheter was placed as prophylaxis in
      51 patients (85%) and as treatment in the 9 patients (15%) with venous
      thromboembolic event. The devices were inserted at the bedside without
      fluoroscopic guidance in 54 patients (90%) and within a median of 4 days after
      hospital admission. They were left in place for a mean of 6 days (4-8 days). One
      patient developed a PE, without hemodynamic compromise; two PEs were averted. No
      serious adverse events were reported. CONCLUSION: Early bedside placement of an
      IVC filter-catheter is possible, and our results suggest that this is a safe,
      effective alternative to short-term PE prophylaxis for high-risk patients with
      contraindications to anticoagulation. LEVEL OF EVIDENCE: Therapeutic study, level
      V.

PMID- 26307881
TI  - Analyzing the effects of alcohol on adolescent trauma using the National Trauma
      Data Bank.
AB  - BACKGROUND: Alcohol misuse is an important source of preventable injuries in the
      adolescent population. The aim of our study was to assess the effect of alcohol
      in adolescent trauma outcomes. METHODS: We performed a retrospective analysis of
      the National Trauma Data Bank (NTDB). Adolescent patients (12-18 years) who were
      tested for alcohol were included in the analysis. Outcome measures were
      difference in complications and mortality between the two groups. RESULTS: A
      total of 31,923 adolescent trauma patients were tested for alcohol; 21% (n =
      6,704) of whom tested positive for alcohol. Propensity-matched analysis revealed
      that adolescent patients with alcohol use were more likely to have adult
      respiratory distress syndrome (10% vs. 6%, p = 0.001), pneumonia (31% vs. 24%, p
      = 0.01), and thromboembolic complications (30% vs. 20%, p = 0.001) during their
      hospitalization. The mortality rate was higher in adolescent trauma patients who
      tested positive for alcohol (15% vs. 9%, p = 0.04). CONCLUSION: Alcohol use is
      associated with significant consequences in adolescent population. Our study
      highlights the increasing use of alcohol in adolescent trauma patients. Strict
      screening criteria in adolescent trauma patients are warranted. LEVEL OF
      EVIDENCE: Epidemiologic/prognostic study, level III.

PMID- 26307882
TI  - Management of severe blunt hepatic injury in the era of computed tomography and
      transarterial embolization: A systematic review and critical appraisal of the
      literature.
AB  - BACKGROUND: During the last decade, the management of blunt hepatic injury has
      considerably changed. Three options are available as follows: nonoperative
      management (NOM), transarterial embolization (TAE), and surgery. We aimed to
      evaluate in a systematic review the current practice and outcomes in the
      management of Grade III to V blunt hepatic injury. METHOD: The MEDLINE database
      was searched using PubMed to identify English-language citations published after
      2000 using the key words blunt, hepatic injury, severe, and grade III to V in
      different combinations. Liver injury was graded according to the American
      Association for the Surgery of Trauma classification on computed tomography (CT).
      Primary outcome analyzed was success rate in intention to treat. Critical
      appraisal of the literature was performed using the validated National Institute
      for Health and Care Excellence "Quality Assessment for Case Series" system.
      RESULTS: Twelve articles were selected for critical appraisal (n = 4,946
      patients). The median quality score of articles was 4 of 8 (range, 2-6). Overall,
      the median Injury Severity Score (ISS) at admission was 26 (range, 0.6-75). A
      median of 66% (range, 0-100%) of patients was managed with NOM, with a success
      rate of 94% (range, 86-100%). TAE was used in only 3% of cases (range, 0-72%)
      owing to contrast extravasation on CT with a success rate of 93% (range, 81
      100%); however, 9% to 30% of patients required a laparotomy. Thirty-one percent
      (range, 17-100%) of patients were managed with surgery owing to hemodynamic
      instability in most cases, with 12% to 28% requiring secondary TAE to control
      recurrent hepatic bleeding. Mortality was 5% (range, 0-8%) after NOM and 51%
      (range, 30-68%) after surgery. CONCLUSION: NOM of Grade III to V blunt hepatic
      injury is the first treatment option to manage hemodynamically stable patients.
      TAE and surgery are considered in a highly selective group of patients with
      contrast extravasation on CT or shock at admission, respectively. Additional
      standardization of the reports is necessary to allow accurate comparisons of the
      various management strategies. LEVEL OF EVIDENCE: Systematic review, level IV.

PMID- 26307883
TI  - Nonopioid management of acute pain associated with trauma: Focus on pharmacologic
      options.

PMID- 26307884
TI  - Traumatic panhypopituitarism resulting in acute adrenal crisis.
AB  - Pituitary function plays an integral role in the physiologic response to
      traumatic injury. A significant proportion of trauma patients develop partial
      pituitary insufficiency. While isolated deficiencies of individual pituitary
      hormones are common, there are few reports in the literature of traumatic pan
      pituitary failure with deficiency of all major pituitary hormones. We present a
      case of a patient involved in a motorcycle accident who sustained a sella turcica
      fracture, epidural hemorrhage, subdural hemorrhage, optic nerve palsy, and
      bilateral abducens nerve palsies. Three days after the accident, the patient
      became hypotensive and progressed to cardiopulmonary arrest. He was resuscitated
      and had spontaneous return of circulation. Despite adequate fluid resuscitation
      and vasopressor support, he remained profoundly hypotensive. Following
      administration of hydrocortisone, his blood pressures dramatically improved. He
      was found to have laboratory abnormalities, suggesting deficiencies of
      corticotropins, somatotropins, thyrotropins, gonadotropins, prolactin, and
      antidiuretic hormone. This is the first reported case of a patient with traumatic
      total panhypopituitarism complicated by acute adrenal crises during initial
      postinjury hospitalization. A review of the literature with comparison with other
      studies of trauma patients with deficiencies in five or more axes is presented. A
      high level of suspicion for central adrenal insufficiency and prompt
      administration of corticosteroids in the setting of symptomatic pituitary trauma
      can result in favorable outcomes. Screening for and treating posttraumatic
      hypopituitarism can result in improved rehabilitation and increased quality of
      life for trauma patients. 

PMID- 26307885
TI  - Clinical assessment of trauma-induced coagulopathy and its contribution to
      postinjury mortality: A TACTIC proposal.

PMID- 26307886
TI  - Defining the space between life and death: Fatal critical illness.

PMID- 26307887
TI  - MESS (Mangled Extremity Severity Score) 25 years on: Time for a reboot?

PMID- 26307888
TI  - A trauma surgeon's journey.

PMID- 26307889
TI  - Surgical stabilization of severe rib fractures: Several caveats.

PMID- 26307890
TI  - Trauma care does not discriminate: The association of race and health insurance
      with mortality following traumatic injury.

PMID- 26307891
TI  - Re: Trauma care does not discriminate: The association of race and health
      insurance with mortality following traumatic injury.

PMID- 26307892
TI  - Safety concerns for rescue providers using sternal intraosseous infusion systems.

PMID- 26307893
TI  - Re: Safety concerns for rescue providers using sternal intraosseous infusion
      systems.

PMID- 26307896
TI  - Refined Insights in the Photochromic spiro-Dihydroindolizine/Betaine System.
AB  - We have revisited the photochromic spiro-dihydroindolizine/betaine system by
      comparing state-of-the-art density functional theory calculations with
      experimental data. Time-dependent density functional theory calculations are
      employed to examine the transformations occurring after photoexcitation. This
      study confirms that photoexcitation of the spiro-dihydroindolizine leads to the
      formation of the cis-betaine. However, isomerization to the trans-betaine follows
      through a complicated and formerly unknown potential energy landscape, which
      consists of a network of transition states and intermediates. The available
      pathways across this potential energy landscape will determine the kinetics of
      the forward reaction from the cis-betaine to the trans-betaine and then, even
      more importantly, the back-reaction. Virtually all practical applications of this
      optical switch rely on these reactions and, therefore, occur within this
      landscape. Predicting the network of transition states and intermediates for
      substituted spiro-dihydroindolizine/betaine systems will enable the in-silico
      design of optical switches with enhanced performance. 

PMID- 26307897
TI  - COMMENTARY ON FASTING VERSUS POSTPRANDIAL HYPERGLYCEMIA AS A TREATMENT TARGET TO
      LOWER ELEVATED A1C.

PMID- 26307898
TI  - PRIMARY HYPERPARATHYROIDISM: COMPARING BETWEEN SOLID AND CYSTIC ADENOMAS AND THE
      EFFICACY OF ULTRASOUND AND SINGLE-PHOTON EMISSION COMPUTED TOMOGRAPHY IN THEIR
      DIAGNOSIS.
AB  - OBJECTIVE: Primary hyperparathyroidism (PHPT) is a disorder that results from
      abnormal functioning of the parathyroid glands. The purpose of this study was to
      compare cystic and solid adenomas by analyzing different variables associated
      with PHPT and parathyroid adenomas (age, calcium, phosphorus, and parathyroid
      hormone [PTH] levels, adenoma volume) while comparing the efficacy of ultrasound
      and single-photon emission computed tomography in differentiating between both
      types of adenoma. METHODS: From 152 patients diagnosed with PHPT between January
      2013 and 2014, only 109 patients who had positive ultrasonographic findings for
      single parathyroid adenoma were included in the study. RESULTS: A total of 26
      patients had cystic adenomas and 83 patients had solid adenomas. Sestamibi (MIBI)
      was negative in 50% of the cystic adenoma group and 27.7% of the solid adenoma
      group, with an overall technetium-MIBI efficacy of 67%. Age, phosphorus level,
      and adenoma volume were significantly higher in patients with cystic adenomas (P
      = .001, P = .02, and P = .02, respectively), whereas calcium and PTH levels were
      significantly higher in patients with solid adenomas (P = .02, P = .038,
      respectively). MIBI had a significant correlation with PTH levels (P = .031) and
      adenoma volume (P = .05) only in patients with solid adenomas. No significant
      correlation was found between sex and type of parathyroid adenoma. CONCLUSION:
      The current study is the first to compare age, PTH levels, and adenoma volume
      between cystic and solid adenoma patients, providing more information for the
      poorly understood pathology of cystic adenomas. Our findings showed that age and
      calcium and PTH levels are significantly higher in patients with solid adenomas,
      whereas adenoma volume and phosphorus levels are significantly higher in patients
      with cystic adenomas.

PMID- 26307899
TI  - COMPARISON OF BASAL INSULIN REGIMENS ON GLYCEMIC VARIABILITY IN NONCRITICALLY ILL
      PATIENTS WITH TYPE 2 DIABETES.
AB  - OBJECTIVE: To evaluate the impact of different subcutaneous basal insulin
      regimens on glycemic variability (GV) and hospital complications in non-intensive
      care unit (ICU) patients with type 2 diabetes (T2D). METHODS: This study is a
      post hoc analysis of 279 general medicine and surgery patients treated with
      either a "Basal Bolus" insulin regimen using glargine once daily and glulisine
      before meals or a "Basal Plus" regimen using glargine once daily plus correction
      doses of glulisine before meals for glucose >140 mg/dL. GV was calculated as mean
      delta (Delta) daily glucose, mean SD, and mean amplitude of glycemic excursions
      (MAGE). RESULTS: Treatment with Basal Bolus and Basal Plus regimens resulted in
      similar mean daily glucose, hypoglycemia, length of stay (LOS), and hospital
      complications (all P>.05). There were no differences in GV between treatment
      groups by Delta change (72.5 +/- 36 vs. 69.3 +/- 34 mg/dL), SD (38.5 +/- 18 vs.
      37.1 +/- 16 mg/dL) and MAGE (67.5 +/- 34 vs. 66.1 +/- 39 mg/dL) (all P>.05).
      Surgery patients treated with Basal Bolus had higher GV compared to those treated
      with Basal Plus (Delta daily glucose and SD: P = .02, MAGE: P = .009), but no
      difference in GV was found between treatment groups for the general medicine
      patients (P>.05). Patients with hypoglycemia events had higher GV compared to
      subjects without hypoglycemia (P<.05), but no association was found between GV
      and hospital complications (P>.05). CONCLUSION: Treating hospitalized, non-ICU,
      diabetic patients with Basal Plus insulin regimen resulted in similar glucose
      control and GV compared to the standard Basal Bolus insulin regimen. Higher GV
      was not associated with hospital complications.

PMID- 26307900
TI  - SGLT-2 INHIBITOR THERAPY ADDED TO GLP-1 AGONIST THERAPY IN THE MANAGEMENT OF
      T2DM.
AB  - OBJECTIVE: To assess the real-world efficacy and safety of canagliflozin therapy
      added to type 2 diabetes mellitus (T2DM) patients who have received a minimum 1
      year of glucagon-like peptide-1 (GLP-1) agonist therapy. METHODS: This pre-post
      observational study assessed the efficacy and safety of canagliflozin in a group
      of T2DM patients from a community endocrinology practice who received GLP-1
      agonist therapy for a minimum of 12 months. The primary study outcome was change
      in mean glycated hemoglobin (HbA1c) level from baseline. Secondary endpoints
      included changes in average weight, and comparison of the percentage of patients
      obtaining an HbA1c <7%. RESULTS: A total of 75 patients met all the study
      criteria. Baseline patient characteristics were as follows: average age, 58 +/- 9
      years; mean duration of T2DM, 14 +/- 6 years; 56% male; 92% Caucasian; baseline
      body mass index (BMI), 39.4 +/- 9.4 kg/m(2); and mean baseline HbA1c, 7.94 +/-
      0.69%. HbA1c and weight were significantly reduced by 0.39% and 4.6 kg,
      respectively. Adverse effects were reported by 13 (17.3%) patients, including 4
      (5.3%) who discontinued canagliflozin because of adverse reactions. CONCLUSION:
      Canagliflozin was generally well tolerated and significantly further reduced mean
      HbA1c levels and body weight in patients with T2DM when added to GLP-1 regimen.

PMID- 26307901
TI  - Visual Vignette.

PMID- 26307902
TI  - FASTING VERSUS POSTPRANDIAL HYPERGLYCEMIA AS A TREATMENT TARGET TO LOWER ELEVATED
      HEMOGLOBIN A1C.
AB  - OBJECTIVE: Postprandial hyperglycemia (PPHG) may need addressing when glycemic
      control cannot be maintained in patients with type 2 diabetes mellitus. We
      investigated whether glycated hemoglobin A1c (A1c) levels >=7.0% can indicate
      postprandial defects warranting prandial therapy after optimized basal insulin
      therapy. METHODS: From 6 clinical trials of insulin glargine treatment, data were
      pooled from 496 patients with A1c >=7.0% after 24 weeks. Patient characteristics
      and clinical outcomes were summarized according to fasting plasma glucose (FPG)
      target achievement (<130 mg/dL), postprandial blood glucose (PPBG) levels, and
      PPBG increments (DeltaPPBG). Basal and postprandial contributions to
      hyperglycemia were determined. RESULTS: After 24 weeks of insulin glargine
      titration, A1c change from baseline was greater in patients with FPG <130 mg/dL
      versus >=130 mg/dL (-1.35% versus -1.11%, respectively; P = .0275), but with
      increased confirmed hypoglycemia rates (blood glucose <70 mg/dL; 4.06
      events/patient-year versus 3.31 events/patient-year; P = .0170). However,
      increased severe hypoglycemia rates were observed in patients with FPG >=130
      mg/dL. At week 24, postprandial contributions to hyperglycemia increased (>60%
      regardless of PPBG). Patients with high FPG had lower, but substantial, relative
      postprandial contributions versus patients achieving FPG target. A similar
      pattern was observed according to whether patients had a DeltaPPBG >=50 mg/dL
      after any meal. CONCLUSION: After optimized basal insulin therapy, elevated A1c
      is the most effective indicator of residual PPHG, regardless of existent FPG or
      PPBG. When confronted with an uncontrolled A1c after reasonable titration of
      basal insulin, clinicians should be aware of probable postprandial contributions
      to hyperglycemia and consider prandial therapy.

PMID- 26307903
TI  - OPTIMIZED HUMAN REGULAR U-500 INSULIN TREATMENT IMPROVES beta-CELL FUNCTION IN
      SEVERELY INSULIN-RESISTANT PATIENTS WITH LONG-STANDING TYPE 2 DIABETES AND HIGH
      INSULIN REQUIREMENTS.
AB  - OBJECTIVE: To assess beta-cell function and insulin sensitivity following
      improvement in glycemic control in severely insulin-resistant patients with
      poorly controlled type 2 diabetes (T2D). METHODS: A subset of patients in a 24
      week, open-label, randomized trial comparing thrice-daily (n = 14/162) versus
      twice-daily (n = 11/163) human regular U-500 insulin (U-500R) underwent mixed
      meal tolerance testing at baseline and endpoint. Baseline characteristics were
      similar between treatment groups (combined means: age, 54.0 years; diabetes
      duration, 13.6 years; body mass index, 38.8 kg/m(2); glycated hemoglobin [HbA1c],
      8.3%; U-100 insulin dose, 287.6 units/day, 2.6 units/kg/day). Primary outcome
      measure was ratio of area under the curve (AUC) for C-peptide to glucose (AUCC
      peptide/AUCglucose) at 24-week endpoint. RESULTS: Change from baseline HbA1c,
      daily U-500R dose, and weight were -1.17% (P = .0002), +80.8 units (P = .0003),
      and +5.9 kg (P = .33), respectively. beta-Cell function significantly improved
      after 24 weeks of U-500R therapy in combined treatment groups. The AUCC
      peptide/AUCglucose increased 34.0% (ratio of least-squares geometric mean, 1.34;
      95% confidence interval, 1.18 to 1.52; P = .0001). Integral of total insulin
      secretion rate increased from 27.0 to 33.7 nmol/m(2), and glucose sensitivity
      improved from 18.3 to 24.0 pmol/min/m(2)/mM (both, P = .02). Matsuda index
      improved from 0.8 to 1.3 (P = .008). CONCLUSION: Despite long-standing diabetes
      and poor glycemic control at baseline, functional recovery of beta-cells was
      observed with improved glycemic control in these severely insulin-resistant
      patients with T2D, possibly due to alleviation of glucotoxicity.

PMID- 26307904
TI  - Media perceptions of Tommy John surgery.
AB  - OBJECTIVES: The prevalence of medial ulnar collateral ligament (UCL)
      reconstruction is increasing in professional athletes and the delivery of
      baseball news by the media exerts a powerful influence on public opinion of the
      injury and surgery. The purpose of this investigation was to examine the media's
      perception regarding the causes of UCL injury as well as the indications, risks,
      benefits, and rehabilitation related to UCL reconstruction. STUDY DESIGN: Cross
      sectional survey study, Level 3. METHODS: This study utilized an online thirty
      question survey designed to assess an individual's perception of UCL
      reconstruction with regard to risk factors for injury, indications, benefits,
      surgical details, and rehabilitation. Eligible study participants were members of
      the media including print, internet, radio and/or television directly involved in
      the coverage of Major League Baseball (MLB). RESULTS: A total of 516 members of
      the media with a mean age of 43.6 years completed the survey. In nearly half
      (47.8%), professional baseball represented 76-100% of their total sports coverage
      responsibility. INDICATIONS: although the majority answered correctly, 45% did
      not know if an athlete needed an elbow injury as a prerequisite for UCL
      reconstruction and 25% believed the primary indication was performance
      enhancement. As percentage of baseball coverage increased, media members were
      less likely to believe that an elbow injury was not required (p = 0.038).
      BENEFITS: eighty percent recognized that pitching speed is typically reduced
      following surgery, but the remaining 20% felt that velocities actually increased
      compared with pre-injury velocities. Return to play: fifty-two percent
      overestimated the ability of pitchers to return to back to professional baseball
      and 51.2% believed return would occur in 12 or less months. Estimates were higher
      in those of older age (p = 0.032) and increased percentage of baseball coverage
      (p < 0.001). Overuse injuries: less than half (48.4%) believed the use of pitch
      counts to be important in the prevention of UCL injury and 33.2% felt that
      throwing injuries were not preventable in adolescent baseball. CONCLUSION: Common
      misconceptions exist regarding UCL reconstruction within the professional
      baseball media. Efforts for physicians to educate the media on the risks of
      overuse throwing injuries with emphasis on accurate indications, outcomes, and
      recovery of Tommy John Surgery are encouraged.

PMID- 26307905
TI  - The transient but not resident (TBNR) microbiome: a Yin Yang model for lung
      immune system.
AB  - The concept of microbial content of the lung is still controversial. What make
      this more complicated are controversial results obtaining from different
      methodologies about lung microbiome and the definition of "lung sterility". Lungs
      may have very low bacteria but are not completely germ-free. Bacteria are
      constantly entering from the upper respiratory tract, but are then quickly being
      cleared. We can find bacterial DNA in the lungs, but it is much harder to ask
      about living bacteria. Here, we propose that if there is any trafficking of the
      microorganisms in the lung, it should be a "Transient But Not Resident (TBNR)"
      model. So, we speculate a "Yin Yang model" for the lung immune system and TBNR.
      Despite beneficial roles of microbiome on the development of lung immune system,
      any disruption and alteration in the microbiota composition of upper and lower
      airways may trigger or lead to several diseases such as asthma, chronic
      obstructive pulmonary disease and mustard lung disease. 

PMID- 26307906
TI  - Gender Differences in Alcohol Use and Risk Drinking in Ontario Ethnic Groups.
AB  - This article examines prevalence and gender differences of alcohol use and risk
      drinking in a representative sample of Ontario adults. Data were drawn from the
      Centre for Addiction and Mental Health (CAMH) Monitor survey of Ontario adults
      aged 18 and older collected between January 2005 and December 2010. The
      prevalence of self-reported lifetime, current, and high-risk drinking were all
      higher among the Canadian and the European-origin groups compared with other
      ethnic groups. Within-group gender differences were evident for all ethnic
      groups. The narrowest gender gap was observed within the North European group and
      the widest in the South Asian group. The non-European ethnic groups had higher
      rates of abstinence and lower alcohol consumption rates; nevertheless, a
      considerable proportion of people from these groups may be at risk of alcohol
      related harm due to risky and harmful alcohol consumption patterns. Future
      research should continue to investigate alcohol use in these groups and identify
      subgroups at risk and factors that increase or decrease their vulnerability to
      risky and problem drinking. 

PMID- 26307907
TI  - Bis-1,3-dipolar Cycloadditions on Endohedral Fullerenes M3N@Ih-C80 (M = Sc, Lu):
      Remarkable Endohedral-Cluster Regiochemical Control.
AB  - In this work, we briefly report some attempts to control regioisomeric
      bisadditions on Sc3N@Ih-C80 and Lu3N@Ih-C80 using the tether-controlled
      multifunctionalization method. We then describe the use of independent
      (nontethered) bis-1,3-dipolar cycloaddition reactions and the characterization of
      5 new bisadducts, 3 for Sc3N@C80 and 2 for Lu3N@C80, which have never been
      reported before. Unexpectedly and remarkably, 4 of these compounds exhibit
      relatively high symmetry and 2 of these bisadducts are the first examples of
      intrinsically chiral endohedral compounds, due to the addition pattern, not to
      the presence of chiral centers on the addends. Since an analysis of the
      statistically possible number of bisadduct isomers on an Ih-C80 cage has not been
      reported, we present it here. 

PMID- 26307908
TI  - Mixis and Diagnosis: Aristotle and the "Chemistry" of the Sublunary World.
AB  - In On Generation and Corruption 1.10, Aristotle introduces the new idea of
      "chemical mixture" (mixis) to explain the constitution of those homogeneous
      substances from which all things in the sublunary world are comprised. In a
      mixture, the ingredients interact with one another to give rise to a new
      substance, qualitatively different, yet preserving the original ingredients in
      potentia, so that they can be separated again. In Book IV of the Meteorologica,
      Aristotle further suggests that bodies may be "diagnosed" according to certain
      passive properties, such as the fusibility of metals. While his theory of mixture
      has often led historians of science to identify Aristotle as one of the
      precursors of chemical science, his ideas have also been criticised as archaic,
      and implicated in a qualitative conception of the cosmos that delayed progress
      towards quantifying natural phenomena. In this paper, I take up the defence of
      Aristotle's theory by showing that his concept of mixture is not an obstacle to
      the development of natural science and chemistry, but, on the contrary, opens the
      way by offering an advanced model of qualitative analysis which does not exclude
      the possibility of quantitative development. 

PMID- 26307909
TI  - Transmutation Theory in the Greek Alchemical Corpus.
AB  - This paper studies transmutation theory as found in the texts attributed to
      Zosimus of Panopolis, "the philosopher Synesius," and "the philosopher
      Olympiodorus of Alexandria." It shows that transmutation theory (i.e. a theory
      explaining the complete transformation of substances) is mostly absent from the
      work attributed to these three authors. The text attributed to Synesius describes
      a gilding process, which is similar to those described by Pliny and Vitruvius.
      The commentary attributed to Olympiodorus is the only text studied here that
      describes something similar to a transmutation theory. It is unclear, however, if
      this was a theory of transmutation or if the writer meant something more like the
      literal meaning of the word "ekstrophe," a term used to describe the
      transformation of metals, as the "turning inside-out" of what is hidden in a
      substance. A similar conception of ekstrophe can be found in the works of
      Zosimus, who discussed transmutation to make an analogy with self-purification
      processes, which, from the perspective of his own anthropogony, consisted in the
      "turning inside-out" of the "inner human" (eso anthropos). 

PMID- 26307910
TI  - If You Don't Have a Good Laboratory, Find a Good Volcano: Mount Vesuvius as a
      Natural Chemical Laboratory in Eighteenth-Century Italy.
AB  - This essay that examines the role of the volcano as a chemical site in the late
      eighteenth century, as the "new chemistry" spread throughout the southern Italian
      Kingdom of Naples, resulting in lively debates. In Naples itself, these
      scientific debates were not confined to academies, courts, and urban spaces. In
      the absence of well-equipped chemical laboratories, Neapolitan scholars also
      carried out research on chemistry on the slopes of Mount Vesuvius, a natural site
      that furnished them with all the tools and substances necessary for practising
      chemistry. By examining various Neapolitan publications on Vesuvius and the
      chemical reactions and products associated with its periodic eruptions, I argue
      that the volcano's presence contributed to a distinctive, local approach to
      chemical theory and practice. Several case studies examine the ways in which
      proximity to Vesuvius was exploited by Neapolitan scholars as they engaged with
      the new chemistry, including Giuseppe Vairo, Michele Ferrara, Francesco Semmola,
      and Emanuele Scotti. 

PMID- 26307911
TI  - Michael Faraday's Contributions to Archaeological Chemistry.
AB  - The analysis of ancient artefacts is a long but largely neglected thread within
      the histories of archaeology and chemistry. This paper examines Michael Faraday's
      contributions to this nascent field, drawing on his published correspondence and
      the works of his antiquarian collaborators, and focusing in particular on his
      analyses of Romano-British and ancient Egyptian artefacts. Faraday examined the
      materials used in ancient Egyptian mummification, and provided the first proof of
      the use of lead glazes on Roman ceramics. Beginning with an assessment of
      Faraday's personal interests and early work on antiquities with Humphry Davy,
      this paper critically examines the historiography of archaeological chemistry and
      attempts to place Faraday's work within its institutional, intellectual, and
      economic contexts. 

PMID- 26307914
TI  - Lack of genetic association of the TGM2 gene with schizophrenia in a Chinese
      population.
AB  - The gene coding for transglutaminase 2 (TGM2) has been reported to be associated
      with schizophrenia in a White population. The present study was then designed to
      replicate this initial finding in a Chinese population. A total of 428
      individuals with schizophrenia and 555 control participants were recruited for
      genetic analysis. Four single nucleotide polymorphisms present in the TGM2 gene
      were selected for genotyping, including rs2076380, rs7270785, rs4811528, and
      rs6023526, by PCR-based restriction fragment length polymorphism analysis. None
      of these four single nucleotide polymorphisms genotyped showed an association
      with schizophrenia, although these 428 cases and 555 controls had 97% power to
      detect a disease association in small effect size (odds ratio=1.5). The present
      results did not support the TGM2 association with schizophrenia. It is thus
      possible that the TGM2 finding may have resulted from a random error of sampling.

PMID- 26307917
TI  - Regulating Underwater Oil Adhesion on Superoleophobic Copper Films through
      Assembling n-Alkanoic Acids.
AB  - Controlling liquid adhesion on special wetting surface is significant in many
      practical applications. In this paper, an easy self-assembled monolayer technique
      was advanced to modify nanostructured copper substrates, and tunable adhesive
      underwater superoleophobic surfaces were prepared. The surface adhesion can be
      regulated by simply varying the chain length of the n-alkanoic acids, and the
      tunable adhesive properties can be ascribed to the combined action of surfaces
      nanostructures and related variation in surface chemistry. Meanwhile, the tunable
      ability is universal, and the oil-adhesion controllability is suitable to various
      oils including silicon oil, n-hexane, and chloroform. Finally, on the basis of
      the special tunable adhesive properties, some applications of our surfaces
      including droplet storage, transfer, mixing, and so on are also discussed. The
      paper offers a novel and simple method to prepare underwater superoleophobic
      surfaces with regulated adhesion, which can potentially be applied in numerous
      fields, for instance, biodetection, microreactors, and microfluidic devices. 

PMID- 26307915
TI  - Intranasal nanoemulsion-based inactivated respiratory syncytial virus vaccines
      protect against viral challenge in cotton rats.
AB  - Respiratory Syncytial Virus is a leading cause of bronchiolitis and pneumonia in
      infants, the elderly and individuals with compromised immune systems. Despite
      decades of research, there is currently no available vaccine for RSV. Our group
      has previously demonstrated that intranasal immunization of mice with RSV
      inactivated by and adjuvanted with W805EC nanoemulsion elicits robust humoral and
      cellular immune responses, resulting in protection against RSV infection. This
      protection was achieved without the induction of airway hyper-reactivity or a Th2
      skewed immune response. The cotton rat Sigmodon hispidus has been used for years
      as an excellent small animal model of RSV disease. Thus, we extended these rodent
      studies to the more permissive cotton rat model. Intranasal immunization of the
      nanoemulsion-adjuvanted RSV vaccines induced high antibody titers and a robust
      Th1-skewed cellular response. Importantly, vaccination provided sterilizing cross
      protective immunity against a heterologous RSV challenge and did not induce
      marked or severe histological effects or eosinophilia in the lung after viral
      challenge. Overall, these data demonstrate that nanoemulsion-formulated whole RSV
      vaccines are both safe and effective for immunization in multiple animal models. 

PMID- 26307918
TI  - A peptide array-based serological protein kinase A activity assay and its
      application in cancer diagnosis.
AB  - Protein kinase A (PKA) plays a crucial role in several biological processes;
      however, there is no assay with sufficient sensitivity and specificity to
      determine serological PKA (sPKA) activity. Here we present an on-chip activity
      assay that employs cysteine-modified kemptide arrays to determine specific sPKA
      activity in human sera that eliminates the potential contributions of other
      kinases with a protein kinase peptide inhibitor. The sensitivity of the on-chip
      sPKA activity assay was greatly enhanced by Triton X-100, with a 0.01 U mL(-1)
      detection limit. sPKA activity was determined by subtracting nonspecific sPK
      activity from total sPK activity. Our assay provided greater sensitivity and
      specificity and more accurate area under the curve values for gastric cancer
      compared to the total sPK activity assay. sPKA activities in human sera from
      patients with hepatic (n = 30), gastric (n = 30), lung (n = 30), and colorectal
      (n = 30) cancers were significantly higher than those in controls (n = 30, p <
      10(-4)), but no significant difference in sPKA activities between normal and
      inflammation groups was observed. These results demonstrate that the on-chip
      assay accurately measures sPKA activity in human sera and that the sPKA activity
      may be a potential biomarker for cancer diagnosis. 

PMID- 26307919
TI  - Effects of dipotassium-trioxohydroxytetrafluorotriborate, K2[B3O3F4OH], on cell
      viability and gene expression of common human cancer drug targets in a melanoma
      cell line.
AB  - Recently it was found that dipotassium-trioxohydroxytetrafluorotriborate,
      K2(B3O3F4OH), is a potent and highly specific inhibitor of precancerous cell
      processes. We conducted gene expression profiling of human melanoma cells before
      and after treatment with two concentrations (0.1 and 1 mM) of this boron
      inorganic derivative in order to assess its effects on deregulation of genes
      associated with tumor pathways. Parallel trypan blue exclusion assay was
      performed to assess the cytotoxicity effects of this chemical. Treatment with
      K2(B3O3F4OH) induced a significant decrease of cell viability in melanoma
      cellline at both tested concentrations. Furthermore, these treatments caused
      deregulation of more than 30 genes known as common anti-tumor drug targets. IGF-1
      and hTERT were found to be significantly downregulated and this result may imply
      potential use of K2(B3O3F4OH) as an inhibitor or human telomerase and insulin
      like growth factor 1, both of which are associated with various tumor pathways. 

PMID- 26307920
TI  - A frozen matrix hybrid optical nonlinear system enhanced by a particle lens.
AB  - In this work, a Graphene Oxide (GO) nano-sheet and SiO2 micro-bead hybrid system
      based on a frozen matrix was investigated for its enhanced optical nonlinear
      performance. A frozen matrix is a novel approach that hosts the optical nonlinear
      nano-particles, which combines the strengths from both liquid and solid phase
      systems for high performance photonic applications. SiO2 micro-beads were used to
      induce a local field enhancement effect that improved the optical nonlinearity of
      GO nano-sheets. The nonlinear performance of the hybrid system is several orders
      higher than the existing GO nano-sheet liquid dispersion. In addition, this
      frozen matrix and the local field enhancement effect are two facile and versatile
      methods that can be applied to many types of nano-particle dispersions. 

PMID- 26307921
TI  - A Vision for Graduate Medical Education.

PMID- 26307922
TI  - A Missed Opportunity to Achieve Excellence in Residency Education.

PMID- 26307923
TI  - In Reply to Wayne et al.

PMID- 26307924
TI  - Graduate Medical Education Reforms Need to Better Serve Program Directors.

PMID- 26307925
TI  - Working Smarter, Not Harder: Assessing Resident Performance Using Brief
      Structured Observation.

PMID- 26307926
TI  - The Benefits and Risks of Asynchronous Education.

PMID- 26307927
TI  - In Reply to Pescatore et al.

PMID- 26307928
TI  - Issues in the Conversation About Graduate Medical Education Reform.

PMID- 26307929
TI  - In Reply to Weissman.

PMID- 26307930
TI  - The Many Faces of the Hospital.

PMID- 26307931
TI  - Being Boring.

PMID- 26307932
TI  - Artist's Statement: Learning to Sew.

PMID- 26307933
TI  - Medicine and the Arts. Death Barged In by Kathleen Sheeder Bonanno. Commentary.

PMID- 26307935
TI  - A novel environmental DNA approach to quantify the cryptic invasion of non-native
      genotypes.
AB  - The invasion of non-native species that are closely related to native species can
      lead to competitive elimination of the native species and/or genomic extinction
      through hybridization. Such invasions often become serious before they are
      detected, posing unprecedented threats to biodiversity. A Japanese native strain
      of common carp (Cyprinus carpio) has become endangered owing to the invasion of
      non-native strains introduced from the Eurasian continent. Here, we propose a
      rapid environmental DNA-based approach to quantitatively monitor the invasion of
      non-native genotypes. Using this system, we developed a method to quantify the
      relative proportion of native and non-native DNA based on a single-nucleotide
      polymorphism using cycling probe technology in real-time PCR. The efficiency of
      this method was confirmed in aquarium experiments, where the quantified
      proportion of native and non-native DNA in the water was well correlated to the
      biomass ratio of native and non-native genotypes. This method provided
      quantitative estimates for the proportion of native and non-native DNA in natural
      rivers and reservoirs, which allowed us to estimate the degree of invasion of non
      native genotypes without catching and analysing individual fish. Our approach
      would dramatically facilitate the process of quantitatively monitoring the
      invasion of non-native conspecifics in aquatic ecosystems, thus revealing a
      promising method for risk assessment and management in biodiversity conservation.

PMID- 26307936
TI  - Global Health Competencies for Physiotherapist Education in the United States.
AB  - INTRODUCTION: Increasingly global health education is being incorporated into
      health professions' curricula. Various disciplines have defined global health
      competencies (GHC) for their areas of professional practice. However,
      physiotherapist educators have not delineated GHC for physiotherapist education.
      This study's purpose was to develop GHC for United States (US)-based
      physiotherapist education. METHODS: We developed an online survey using 30 GHC
      from a nursing study and 4 GHC that we developed. We recruited physiotherapists
      who were clinicians and/or faculty employed in the US, or who had been employed
      as clinicians and/or faculty in the US within the past 5 years to complete the
      survey. We examined descriptive data for Likert responses and used content
      analysis for analysis of open-ended responses. The University of Texas at El Paso
      Institutional Review Board granted exempt status for the study. RESULTS: One
      hundred eighty-eight participants completed the survey. A majority agreed or
      strongly agreed that 33 of the total 34 GHC were relevant to physiotherapist
      education. Four major categories emerged from open-ended responses: beyond entry
      level, greater relevance to physiotherapy, emphasis on US concerns, and value of
      understanding international issues and perspectives. DISCUSSION: Although most
      participants agreed with the GHC, open-ended responses indicated the need for
      revision of the GHC to make them more relevant to entry-level physiotherapist
      education. We plan to revise the GHC and then validate the modified GHC through a
      future Delphi study. Study limitations include the limited number of participants
      and that the lack of an operational definition of 'global health' may have
      created confusion. IMPLICATIONS FOR PHYSIOTHERAPY PRACTICE: The study's results
      may inform physiotherapist educators inside and outside of the US as they contend
      with determining how to most effectively prepare physiotherapist students for
      competent practice in a globalized world. Copyright (c) 2015 John Wiley & Sons,
      Ltd.

PMID- 26307937
TI  - Labelling errors in fine needle aspiration cytology.

PMID- 26307938
TI  - Genetic vs Environmental Factors That Correlate With Rosacea: A Cohort-Based
      Survey of Twins.
AB  - IMPORTANCE: To our knowledge, this is the first study on rosacea to formally
      define genetic and environmental contributions. OBJECTIVES: To study a cohort of
      identical and fraternal twins to determine whether genetic factors contribute to
      rosacea development and, if genetic factors are present, quantitatively estimate
      the genetic contribution, as well as to identify environmental factors that
      correlate with rosacea by controlling for genetic susceptibility. DESIGN,
      SETTING, AND PARTICIPANTS: Identical and fraternal twins were surveyed regarding
      risk factors implicated in rosacea. Faculty dermatologists determined a rosacea
      score for each twin participant according to the National Rosacea Society (NRS)
      grading system. Data were collected at the annual Twins Days Festival in
      Twinsburg, Ohio, on August 4-5, 2012, and August 2-3, 2013. Analysis was
      conducted for several months after each meeting. A cohort of 550 twin
      individuals, with most from Ohio, Pennsylvania, and the northeastern United
      States, participated. MAIN OUTCOMES AND MEASURES: The NRS score and rosacea
      subtype were assessed using the NRS grading system and physical examination by
      board-certified dermatologists. RESULTS: Among the 275 twin pairs (550
      individuals), there were 233 identical twin pairs with a mean rosacea score of
      2.46 and 42 fraternal twin pairs with a mean rosacea score of 0.75. We observed a
      higher association of NRS scores between identical vs fraternal twins (r = 0.69
      vs r = 0.46; P = .04), demonstrating a genetic contribution. Using the ACE model
      (proportion of variance in a trait heritable secondary to additive genetics [A]
      vs the proportions due to a common environment [C] and unique environment [E]),
      we calculated this genetic contribution to be 46%. A higher NRS score was also
      significantly associated with the following factors: age (r = 0.38; P < .001) and
      lifetime UV radiation exposure (r = 0.26; P < .001). These associations remained
      after use of propensity score matching to adjust for multicollinearity. Other
      correlated variables included body mass index (r = 0.21; P < .001), smoking (r =
      0.10; P < .02), alcohol consumption (r = 0.11; P = .01), cardiovascular
      comorbidity (r = 0.17; P < .001), and skin cancer comorbidity (r = 0.19; P <
      .001). CONCLUSIONS AND RELEVANCE: The study of twins allows us to separate
      genetic susceptibility and the influence of environmental factors affecting
      rosacea. We found that approximately half of the contribution to the NRS score
      could be accounted for by genetics and the other half by environment. We
      identified correlations between rosacea and UV radiation exposure, alcohol,
      smoking, skin cancer history, cardiac comorbidity, and age. These findings may
      help improve current management and expectations of individuals affected by
      rosacea.

PMID- 26307939
TI  - Population-based assessment of determining predictors for quality of prostate
      cancer surveillance.
AB  - BACKGROUND: Despite recent interest in the overdiagnosis and overtreatment of
      prostate cancer, the acceptance of expectant management for patients with
      indolent prostate cancer has remained slow. Moreover, the intensity of
      surveillance strategies remains to be elucidated. The objective of this study was
      to determine the population-based intensity of surveillance strategy among
      patients diagnosed with localized prostate cancer who undergo watchful
      waiting/active surveillance and those who receive active treatment. METHODS:
      Linked Surveillance, Epidemiology, and End Results (SEER)-Medicare data were used
      to identify men diagnosed with prostate cancer from 2004 to 2007 who were
      followed until December 31, 2009. Bivariate and multivariate regression analyses
      were used to quantify the use of prostate-specific antigen tests, office visits,
      and second prostate biopsies within 2 years of diagnosis. RESULTS: Compared with
      patients who were receiving active treatment, those who were undergoing watchful
      waiting/active surveillance were less likely to receive prostate-specific antigen
      testing and to attend office visits within the 2 years after diagnosis (P < .01).
      Of the 3656 patients who were undergoing watchful waiting/active surveillance,
      only 166 (4.5%) were on active surveillance (according to the authors' a priori
      definition), although the number increased over the last 2 years of the study
      (hazard ratio, 2.18; 95% confidence interval, 1.28-3.71; P < .01). Limitations of
      the study included data limited to men aged 65 years or older and the lack of
      ability to discern between watchful waiting and active surveillance. CONCLUSIONS:
      Active surveillance is underused, and there is uncertainty regarding the quality
      of surveillance for patients who undergo watchful waiting/active surveillance.
      Further research is needed into qualitatively describing the contributing factors
      that drive decision-making recommendations as well as improved surveillance
      measures for patients with prostate cancer.

PMID- 26307941
TI  - Characteristics of patients treated for orbital cellulitis: An analysis of
      inpatient data.
AB  - OBJECTIVES/HYPOTHESIS: Orbital cellulitis represents a spectrum of diseases, some
      of which may progress to potentially serious complications. The authors used the
      Nationwide Inpatient Sample (NIS) database to analyze the epidemiologic features
      of pediatric and adult patients admitted for the treatment of orbital cellulitis
      and to examine associations with surgical management. METHODS: The NIS was
      queried for patients admitted for treatment of orbital cellulitis from 2002 to
      2010. Patient demographics, length of stay, hospital charges, and concomitant
      diagnoses were analyzed. RESULTS: There were 14,149 cases of orbital cellulitis
      identified with 1,717 (12.1%) having undergone surgical management. Surgical
      patients were older (29.6 +/- 23.4) and more commonly male (62.0%) (P = 0.004 and
      < 0.001, respectively). Patients who had surgical intervention had longer length
      of stay and higher hospital charges than nonsurgical patients (P < 0.001). Our
      study showed that the proportion of pediatric patients age 10 to 19 years (22.1%)
      undergoing surgery was four times that of patients < 5 years of age (5.1%) (P <
      0.001). Patients with concomitant diagnoses of acute and chronic sinusitis, acute
      osteomyelitis, exophthalmos, diplopia, and conjunctival edema had significantly
      increased odds ratio of surgical intervention. Frontal sinusitis was the site
      most commonly associated with surgical intervention among sinusitis patients.
      CONCLUSION: This study describes the characteristics of pediatric and adult
      patients admitted for orbital cellulitis from a national perspective. Patients 10
      to 19 years of age were most likely to undergo surgical management. Acute and
      chronic sinusitis, acute osteomyelitis, exophthalmos, diplopia, and conjunctival
      edema were concomitant diagnoses associated with significantly increased odds
      ratio of surgical intervention. LEVEL OF EVIDENCE: 2C. Laryngoscope, 126:554-559,
      2016.

PMID- 26307940
TI  - Differences in mortality and morbidity according to gestational ages and birth
      weights in infants with trisomy 18.
AB  - The aim of this study was to clarify the effects of gestational age and birth
      weight on outcomes of the infants. Medical records of 36 infants with trisomy 18
      admitted to Tokyo Women's Medical University Hospital from 1991 to 2012 were
      reviewed retrospectively. We compared clinical characteristics between term
      infants (n = 15) and preterm infants (n = 21). There were one very-low-birth
      weight (VLBW) term infant (5%) and 12 VLBW preterm infants (80%). Although there
      were no significant differences in clinical characteristics and provided
      management between the two groups, none of the preterm infants achieved survival
      to discharge. On the other hand, 6 of 21 term infants (29%) achieved survival to
      discharge (P < 0.05). Similar results were obtained for comparisons between the
      VLBW infants and non-VLBW infants. Multiple logistic regression analysis revealed
      that shorter gestational age had a more negative impact than lower birth weight
      to survival to discharge in infants with trisomy 18. In both preterm and term
      groups, the infants who died before 30 days commonly died of respiratory failure
      or apnea. Whereas, the infants who survived more than 30 days mostly died of
      heart failure.

PMID- 26307943
TI  - Design, characterization and cellular uptake studies of fluorescence-labeled
      prototypic cathepsin inhibitors.
AB  - Besides their extracellular activity crucial for several pathophysiological
      conditions, human cysteine cathepsins, in particular cathepsins K and S,
      represent important intracellular targets for drug development. In the present
      study, a prototypic dipeptide nitrile inhibitor structure was equipped with a
      coumarin moiety to function as a fluorescent reporter group. In a second
      inhibitor, a PEG linker was introduced between the dipeptide nitrile and the
      fluorophore. These tool compounds 6 and 7 were characterized by kinetic
      investigations as covalent reversible inhibitors of human cathepsins L, S, K and
      B. Probe 6 showed a pronounced inhibitory activity against cathepsins K and S,
      which was corroborated by modeling of inhibition modes. Probe 7 was highly potent
      (Ki = 93 nM) and selective for cathepsin S. To examine the ability of both probes
      to enter living cells, human embryonic kidney 293 cells were targeted. At a
      concentration of 10 MUM, cellular uptake of probe 6 was demonstrated by
      fluorescence measurement after an incubation time of 30 min and 3 h,
      respectively. The probe's concentration in cell lysates was ascertained on the
      basis of the emission at 492 nm upon excitation at 450 nm, and the results were
      expressed as concentrations of probe 6 relative to the protein concentration
      originating from the lysate. After incubation of 10 MUM of probe 6 for 3 h, the
      cellular uptake was confirmed by fluorescence microscopy. HPLC was used to assess
      the probes' lipophilicity, and the obtained

PMID- 26307944
TI  - Utility of real-time field control in T2 *-Weighted head MRI at 7T.
AB  - PURPOSE: Real-time field control can serve to reduce respiratory field
      perturbations during T2 * imaging at high fields. This work investigates the
      effectiveness of this approach in relation to key variables such as patient
      physique, breathing patterns, slice location, and the choice of sequence.
      METHODS: To cover variation in physical constitution and breathing behavior,
      volunteers with a wide range of body-mass-indices were asked to breathe either
      normally or deeply during T2 *-weighted image acquisition at 7T. Ensuing field
      fluctuation was countered by real-time field control or merely recorded in
      reference experiments. The impact of the control system on image quality was
      assessed by classifying and grading artifacts related to field fluctuation.
      RESULTS: The amplitude of respiratory field changes and related artifacts were
      generally stronger for subjects with higher body-mass-index and for lower slices.
      Field control was found effective at mitigating all five types of artifacts that
      were studied. Overall image quality was systematically improved. Residual
      artifacts in low slices are attributed to insufficient spatial order of the
      control system. CONCLUSION: Real-time field control was found to be a robust
      means of countering respiratory field perturbations in variable conditions
      encountered in high-field brain imaging. Reducing net fluctuation, it generally
      expands the feasibility of high-field T2 * imaging toward challenging patients
      and brain regions. Magn Reson Med 76:430-439, 2016. (c) 2015 Wiley Periodicals,
      Inc.

PMID- 26307942
TI  - Outcomes from a computer-assisted intervention simultaneously targeting cannabis
      and tobacco use.
AB  - BACKGROUND: Cannabis users frequently report concurrent tobacco use, and tobacco
      use is associated with poorer outcomes during treatment for cannabis use
      disorders (CUD). Interventions that simultaneously target both tobacco and
      cannabis use disorders may enhance cessation outcomes for either or both
      substances. METHODS: This study evaluated an intervention integrating highly
      effective treatments for cannabis and tobacco use disorders. Thirty-two
      participants meeting diagnostic criteria for CUD and reporting daily tobacco use
      were enrolled in a 12-week computer-assisted behavioral treatment for CUD.
      Participants were encouraged to participate in a tobacco intervention that
      included a computer-assisted behavioral treatment tailored for tobacco and
      cannabis co-users, and nicotine-replacement therapy (NRT). Cannabis and tobacco
      outcomes were evaluated using descriptive statistics and were compared to a
      historical control group that received treatment for CUD but not tobacco.
      RESULTS: Participants achieved 3.6+/-4.3 consecutive weeks of cannabis
      abstinence, which was comparable to the historical control group (3.1+/-4.4). A
      majority of the sample (78%) completed at least one tobacco module and 44%
      initiated NRT. Over half (56%) initiated tobacco quit attempts, and 28% were
      tobacco abstinent for at least two consecutive weeks. Participants showed greater
      reduction in tobacco use (cigarettes per day) than the historical control group,
      but differences in tobacco abstinence rates during the final month of treatment
      were not statistically significant (12.5% vs. 4%). CONCLUSION: Findings suggest
      that providing a tobacco intervention during treatment for CUD is feasible and
      may positively impact tobacco use without negatively affecting cannabis use
      outcomes.

PMID- 26307945
TI  - Ixodes tick saliva suppresses the keratinocyte cytokine response to TLR2/TLR3
      ligands during early exposure to Lyme borreliosis.
AB  - Ixodes hard tick induces skin injury by its sophisticated biting process. Its
      saliva plays a key role to enable an efficient blood meal that lasts for several
      days. We hypothesized that this feeding process may also be exploited by
      pathogens to facilitate their transmission, especially in the context of
      arthropod-borne diseases. To test this, we used Lyme borreliosis as a model. This
      bacterial infection is caused by Borrelia burgdorferi sensu lato transmitted by
      Ixodes. We co-incubated Borrelia with human keratinocytes in the presence of poly
      (I: C), a dsRNA TLR3 agonist generated by skin injury. This induced a strong
      cytokine response from human primary keratinocytes that was much greater than
      that induced by Borrelia alone. OspC, a TLR2/1 agonist and a major surface
      lipoprotein of Borrelia also amplified the process. Interestingly, tick saliva
      inhibited cytokine responses by keratinocytes to these TLR agonists. We propose
      that Borrelia uses the immunoprivileged site produced by tick saliva to
      facilitate its transmission. 

PMID- 26307946
TI  - Lung surfactants and different contributions to thin film stability.
AB  - The surfactant lining the walls of the alveoli in the lungs increases pulmonary
      compliance and prevents collapse of the lung at the end of expiration. In
      premature born infants, surfactant deficiency causes problems, and lung
      surfactant replacements are instilled to facilitate breathing. These pulmonary
      surfactants, which form complex structured fluid-fluid interfaces, need to spread
      with great efficiency and once in the alveolus they have to form a thin stable
      film. In the present work, we investigate the mechanisms affecting the stability
      of surfactant-laden thin films during spreading, using drainage flows from a
      hemispherical dome. Three commercial lung surfactant replacements Survanta,
      Curosurf and Infasurf, along with the phospholipid dipalmitoylphosphatidylcholine
      (DPPC), are used. The surface of the dome can be covered with human alveolar
      epithelial cells and experiments are conducted at the physiological temperature.
      Drainage is slowed down due to the presence of all the different lung surfactant
      replacements and therefore the thin films show enhanced stability. However, a
      scaling analysis combined with visualization experiments demonstrates that
      different mechanisms are involved. For Curosurf and Infasurf, Marangoni stresses
      are essential to impart stability and interfacial shear rheology does not play a
      role, in agreement with what is observed for simple surfactants. Survanta, which
      was historically the first natural surfactant used, is rheologically active. For
      DPPC the dilatational properties play a role. Understanding these different modes
      of stabilization for natural surfactants can benefit the design of effective
      synthetic surfactant replacements for treating infant and adult respiratory
      disorders. 

PMID- 26307947
TI  - Multimodal approach to explore the pathogenicity of BARD1, ARG 658 CYS, and ILE
      738 VAL mutants.
AB  - BARD1-BRCA1 complex plays an important role in DNA damage repair, apoptosis,
      chromatin remodeling, and other important processes required for cell survival.
      BRCA1 and BARD1 heterodimer possess E3 ligase activity and is involved in genome
      maintenance, by functioning in surveillance for DNA damage, thereby regulating
      multiple pathways including tumor suppression. BRCT domains are evolutionary
      conserved domains present in different proteins such as BRCA1, BARD1, XRCC, and
      MDC1 regulating damage response and cell-cycle control through protein-protein
      interactions. Nonetheless, the role of BARD1BRCT in the recruitment of DNA repair
      mechanism and structural integrity with BRCA1 complex is still implicit. To
      explicate the role of BARD1BRCT in the DNA repair mechanism, in silico, in vitro,
      and biophysical approach were applied to characterize BARD1 BRCT wild-type and
      Arg658Cys and Ile738Val mutants. However, no drastic secondary and tertiary
      structural changes in the mutant proteins were observed. Thermal and chemical
      denaturation studies revealed that mutants Arg658Cys and Ile738Val have a
      decrease in Tm and ?G than the wild type. In silico studies of BARD1 BRCT (568
      777) and mutant protein indicate loss in structural compactness on the Ile738Val
      mutant. Comparative studies of wild-type and mutants will thus be helpful in
      understanding the basic role of BARD1BRCT in DNA damage repair. 

PMID- 26307949
TI  - Branching of poly(ADP-ribose): Synthesis of the Core Motif.
AB  - The synthesis of the core motif of branched poly(adenosine diphosphate ribose)
      (poly(ADPr)) is described, and structural analysis reasserted the proposed
      stereochemistry for branching. For the synthesis, a ribose trisaccharide was
      first constructed with only alpha-O-glycosidic linkages. Finally, the adenine
      nucleobase was introduced via a Vorbruggen-type glycosylation reaction. The
      orthogonality of the selected protecting groups was demonstrated, allowing for
      the construction of branched poly(ADPr) oligomers in the near future. 

PMID- 26307950
TI  - Comment on: Wnt Signaling Inhibits Osteoclast Differentiation by Activating
      Canonical and Non-Canonical cAMP/PKA Pathways.

PMID- 26307951
TI  - Selective amination of aryl chlorides catalysed by Ni(PMe3)4.
AB  - C,N-coupling reactions of aryl chlorides and aryl amines catalyzed by a nickel
      catalyst are reported. 17 new amines are synthesized in yields of 57-99%. 2,6
      Dichloro substituted imines can be selectively aminated. Both mono- and di
      aminated products are obtained. Different substrates and amines are tested to
      look into the influence of electronic effects and steric hindrance to the
      reaction. An inexpensive and convenient base, NaOH, is used. It is an efficient
      way to gain access to new amines and imines. 

PMID- 26307952
TI  - Wigner Crystal and Colossal Magnetoresistance in InSb Doped with Mn.
AB  - We report magnetotransport investigation of nonmagnetic InSb single crystal doped
      with manganese at Mn concentration NMn ~ 1,5 * 10(17) cm(-3) in the temperature
      range T = 300 K-40 mK, magnetic field B = 0-25T and hydrostatic pressure P = 0-17
      kbar. Resistivity saturation was observed in the absence of magnetic field at
      temperatures below 200 mK while applied increasing external magnetic field
      induced colossal drop of resistivity (by factor 10(4)) at B ~ 4T with further
      gigantic resistivity increase (by factor 10(4)) at 15T. Under pressure, P = 17
      kbar, resistivity saturation temperature increased up to 1,2 K. Existing models
      are discussed in attempt to explain resistivity saturation, dramatic influence of
      magnetic field and pressure on resistivity with the focus on possible
      manifestation of three dimensional Wigner crystal formed in InSb by light
      electrons and heavy holes. 

PMID- 26307953
TI  - A Triphasic Change of Cardiac Autonomic Nervous System During Electroconvulsive
      Therapy.
AB  - OBJECTIVES: Dynamic autonomic activity changes have been repeatedly reported
      during electroconvulsive therapy (ECT). However, the specific timing of these
      changes remains unclear. To clarify whether sympathetic or parasympathetic
      nervous activity contributes separately to the second stage and the third stage
      during and after induced seizures by ECT, we examined heart rate (HR) and
      spectral analysis of variability (HRV) during ECT. METHODS: Seventeen patients
      with depression participated in the study and underwent ECT. The R-R intervals
      (RRI) were recorded and analyzed sequentially for the HRV indices high-frequency
      (HF) (an index of parasympathetic activity) and low-frequency (LF)/high-frequency
      (an index of sympathetic activity) for 4 minutes before and after stimulus onset
      by the maximum entropy method. Averaged HRs were compared between 3 heart beats
      prestimulus and poststimulus onset. The HRV power in the range of 30 to 80 and 80
      to 130 seconds after a seizure was compared between the HF and LF/HF components.
      RESULTS: There was a significant reduction of the averaged HR over 3 HRs just
      after stimulus onset, suggesting parasympathetic dominance in the first phase.
      The LF/HF power significantly increased in the 30 to 80 s range after stimulus
      onset, whereas the HF power significantly increased in the 80 to 130 s range
      after stimulus onset, reflecting sympathetic activation in the second phase and
      parasympathetic activation in the third phase, respectively. CONCLUSIONS: The
      evaluation of HR and HRV revealed a triphasic change from parasympathetic to
      sympathetic to parasympathetic cardiac autonomic activity after ECT stimulus
      onset in depression patients.

PMID- 26307954
TI  - Anti-TNFalpha therapy for inflammatory bowel diseases is associated with Epstein
      Barr virus lytic activation.
AB  - Anti-TNFalpha therapy, known to suppress T-cell immunity, is increasingly gaining
      popularity for treatment of autoimmune diseases including inflammatory bowel
      diseases (IBD). T-cell suppression increases the risk of B-cell EBV
      lymphoproliferative diseases and lymphomas. Since EBV-lytic activation is
      essential for development of EBV-lymphomas and there have been reports of EBV
      lymphomas in patients treated with anti-TNFalpha therapy, we investigated if
      patients treated with anti-TNFalpha antibodies demonstrate greater EBV-lytic
      activity in blood. Peripheral blood mononuclear cells from 10 IBD patients solely
      on anti-TNFalpha therapy compared to 3 control groups (10 IBD patients not on
      immunosuppressive therapy, 10 patients with abdominal pain but without IBD, and
      10 healthy subjects) were examined for the percentage of T-cells, EBV load and
      EBV-lytic transcripts. Patients on anti-TNFalpha therapy had significantly fewer
      T-cells, greater EBV load, and increased levels of transcripts from EBV-lytic
      genes of all kinetic classes compared to controls. Furthermore, exposure of EBV
      infected B-cell lines to anti-TNFalpha antibodies resulted in increased levels of
      BZLF1 mRNA; BZLF1 encodes for ZEBRA, the viral latency-to-lytic cycle switch.
      Thus, IBD patients treated with anti-TNFalpha antibodies have greater EBV loads
      likely due to enhanced EBV-lytic gene expression and anti-TNFalpha antibodies may
      be sufficient to activate the EBV lytic cycle. Findings from this pilot study lay
      the groundwork for additional scientific and clinical investigation into the
      effects of anti-TNFalpha therapy on the life cycle of EBV, a ubiquitous oncovirus
      that causes lymphomas in the setting of immunocompromise.

PMID- 26307955
TI  - A New Ionone Glycoside and Three New Rhemaneolignans from the Roots of Rehmannia
      glutinosa.
AB  - A new ionone glycoside, frehmaglutoside I (1), and three new rhemaneolignans A-C
      (2-4) were isolated from the 95% EtOH extract of the roots of Rehmannia
      glutinosa. Their structures were determined by extensive spectroscopic (UV, IR,
      HR-ESI-MS, 1D and 2D NMR) analyses. In addition, these compounds were evaluated
      for their protective effects on cardiocytes impaired by doxorubicin in H9c2
      cells. Among them, compounds 1-3 exhibited protective effects against DOX-induced
      cardiotoxicity. 

PMID- 26307956
TI  - Synthesis and Evaluation of Selected Benzimidazole Derivatives as Potential
      Antimicrobial Agents.
AB  - A library of 53 benzimidazole derivatives, with substituents at positions 1, 2
      and 5, were synthesized and screened against a series of reference strains of
      bacteria and fungi of medical relevance. The SAR analyses of the most promising
      results showed that the antimicrobial activity of the compounds depended on the
      substituents attached to the bicyclic heterocycle. In particular, some compounds
      displayed antibacterial activity against two methicillin-resistant Staphylococcus
      aureus (MRSA) strains with minimum inhibitory concentrations (MICs) comparable to
      the widely-used drug ciprofloxacin. The compounds have some common features;
      three possess 5-halo substituents; two are derivatives of (S)-2
      ethanaminebenzimidazole; and the others are derivatives of one 2-(chloromethyl)
      1H-benzo[d]imidazole and (1H-benzo[d]imidazol-2-yl)methanethiol. The results from
      the antifungal screening were also very interesting: 23 compounds exhibited
      potent fungicidal activity against the selected fungal strains. They displayed
      equivalent or greater potency in their MIC values than amphotericin B. The 5
      halobenzimidazole derivatives could be considered promising broad-spectrum
      antimicrobial candidates that deserve further study for potential therapeutic
      applications. 

PMID- 26307957
TI  - Optimal Energy Transfer in Light-Harvesting Systems.
AB  - Photosynthesis is one of the most essential biological processes in which
      specialized pigment-protein complexes absorb solar photons, and with a remarkably
      high efficiency, guide the photo-induced excitation energy toward the reaction
      center to subsequently trigger its conversion to chemical energy. In this work,
      we review the principles of optimal energy transfer in various natural and
      artificial light harvesting systems. We begin by presenting the guiding
      principles for optimizing the energy transfer efficiency in systems connected to
      dissipative environments, with particular attention paid to the potential role of
      quantum coherence in light harvesting systems. We will comment briefly on photo
      protective mechanisms in natural systems that ensure optimal functionality under
      varying ambient conditions. For completeness, we will also present an overview of
      the charge separation and electron transfer pathways in reaction centers.
      Finally, recent theoretical and experimental progress on excitation energy
      transfer, charge separation, and charge transport in artificial light harvesting
      systems is delineated, with organic solar cells taken as prime examples. 

PMID- 26307958
TI  - Ultrasound-Assisted Aqueous Two-Phase System for Extraction and Enrichment of
      Zanthoxylum armatum Lignans.
AB  - In the study, an aqueous two phase system (ATPS) coupled with ultrasound was
      employed to extract lignans from Zanthoxylum armatum. Three standard lignans,
      namely (-)-fargesin, sesamin and L-asarinin, were used as marker compounds, and
      extraction was optimized and projected by response surface methodology (RSM) and
      artificial neural network (ANN). The optimal condition for ATPS with 20% n
      propanol and 24% (NH4)2SO4 coupled with ultrasonic-assisted extraction including
      a solvent to solid ratio of 15:1, a temperature of 40  degrees C, and a treatment
      time of 55 min was obtained. Under the condition, the yield of (-)-fargesin
      increased 15.12%, and the purities of (-)-fargesin, sesamin and L-asarinin
      reached 2.222%, 1.066%, and 1.583%, with an increase of 44.38%, 25.70%, and
      26.34% compared to those extracted with 95% ethanol, respectively. Coefficient of
      the determined (0.9855) and mean squared error (0.0018) of ANN model suggested
      good fitness and generalization of the ANN. Taken together, the results showed
      that ultrasonic-assisted ATPS can be a suitable method for extraction and
      enrichment of lignans from Z. armatum. 

PMID- 26307959
TI  - Design and Synthesis of Imidazopyrazolopyridines as Novel Selective COX-2
      Inhibitors.
AB  - The usefulness of non-steroidal anti-inflammatory drugs (NSAIDs) is hampered by
      their gastrointestinal side effects. Non-selective cyclooxygenases inhibitors
      interfere with both COX-1 and COX-2 isozymes. Since COX-1 mediates cytoprotection
      of gastric mucosa, its inhibition leads to the undesirable side effects. On the
      other hand, COX-2 is undetectable in normal tissues and selectively induced by
      inflammatory stimuli. Therefore, it is strongly believed that the therapeutic
      benefits derive from inhibition of COX-2 only. The presence of a strong
      connection between reported COX-2 inhibitors and cardiac toxicity encourages
      medicinal chemists to explore new scaffolds. In the present study, we introduced
      imidazopyrazolopyridines as new potent and selective COX-2 inhibitors that lack
      the standard pharmacophoric binding features to hERG. Starting from our lead
      compound 5a, structure-based drug-design was conducted and more potent analogues
      were obtained with high COX-2 selectivity and almost full edema protection, in
      carrageenan-induced edema assay, in case of compound 5e. Increased bulkiness
      around imidazopyrazolopyridines by adding a substituted phenyl ring(s) afforded
      less active compounds. 

PMID- 26307960
TI  - Optimization of Micellar Electrokinetic Chromatography Method for the
      Simultaneous Determination of Seven Hydrophilic and Four Lipophilic Bioactive
      Components in Three Salvia Species.
AB  - A micellar electrokinetic chromatography (MEKC) method was developed for the
      simultaneous determination of seven hydrophilic phenolic acids and four
      lipophilic tanshinones in three Salvia species. In normal MEKC mode using SDS as
      surfactant, the investigated 11 compounds could not be well separated. Therefore,
      several buffer modifiers including beta-cyclodextrins (beta-CD), ionic liquid 1
      butyl-3-methylimidazolium tetrafluoroborate ([bmim]BF4) and organic solvents have
      been added to the buffer solution to improve the separation selectivity. Under
      the optimized conditions (BGE, 15 mM sodium tetraborate with 10 mM SDS, 5 mM beta
      CD, 10 mM [bmim]BF4 and 15% ACN (v/v) as additives; buffer pH, 9.8; voltage, 20
      kV; temperature, 25  degrees C), the 11 investigated analytes could achieve
      baseline separation in 34 min. The proposed MEKC was additionally validated by
      evaluating the linearity (R(2) >= 0.9965), LODs (0.27-1.39 MUg.mL(-1)), and
      recovery (94.26%-105.17%), demonstrating this method was reproducible, accurate
      and reliable. Moreover, the contents of the 11 compounds in three Salvia species,
      including S. miltiorrhiza, S. przewalskii and S. castanea were analyzed. The
      result showed that the established MEKC method was simple and practical for the
      simultaneous determination of the hydrophilic and lipophilic bioactive components
      in Salvia species, which could be used to effectively evaluate the quality of
      these valued medicinal plants. 

PMID- 26307961
TI  - Aqueous Extract of Tomato (Solanum lycopersicum L.) and Ferulic Acid Reduce the
      Expression of TNF-alpha and IL-1beta in LPS-Activated Macrophages.
AB  - Acute inflammation is essential for defending the body against pathogens;
      however, when inflammation becomes chronic, it is harmful to the body and is part
      of the pathophysiology of various diseases such as Diabetes Mellitus type 2 (DM2)
      and Cardiovascular Disease (CVD) among others. In chronic inflammation
      macrophages play an important role, mainly through the secretion of
      proinflammatory cytokines such as Tumor necrosis factor (TNF)-alpha and
      Interleukin (IL)-1beta, explained in part by activation of the Toll-like receptor
      4 (TLR4), a signaling pathway which culminates in the activation of Nuclear
      factor (NF)-kappaB, an important transcription factor in the expression of these
      proinflammatory genes. On the other hand, the benefits on health of a diet rich
      in fruit and vegetables are well described. In this work, the effects of aqueous
      extract of tomato and ferulic acid on the expression of proinflammatory cytokines
      in LPS activated monocyte-derived THP-1 macrophages were investigated. In
      addition, using Western blot, we investigated whether the inhibition was due to
      the interference on activation of NF-kappaB. We found that both the tomato
      extract and ferulic acid presented inhibitory activity on the expression of TNF
      alpha and IL-1beta cytokine by inhibiting the activation of NF-kappaB. The
      current results suggest that tomatoes and ferulic acid may contribute to
      prevention of chronic inflammatory diseases. 

PMID- 26307962
TI  - alpha-Glucosidase Inhibitors from Vauquelinia corymbosa.
AB  - The alpha-glucosidase inhibitory activity of an aqueous extract and compounds
      from the aerial parts of V. corymbosa was demonstrated with yeast and rat small
      intestinal alpha-glucosidases. The aqueous extract inhibited yeast alpha
      glucosidase with a half maximal inhibitory concentration (IC50) of 28.6 MUg/mL.
      Bioassay-guided fractionation of the extract led to the isolation of several
      compounds, including one cyanogenic glycoside [prunasin (1)], five flavonoids [(
      )-epi-catechin (2), hyperoside (3), isoquercetin (4), quercitrin (5) and
      quercetin-3-O-(6''-benzoyl)-beta-galactoside (6)] and two simple aromatic
      compounds [picein (7) and methylarbutin (8)]. The most active compound was 6 with
      IC50 values of 30 MUM in the case of yeast alpha-glucosidase, and 437 MUM in the
      case of the mammalian enzyme. According to the kinetic analyses performed with
      rat and yeast enzymes, this compound behaved as mixed-type inhibitor; the
      calculated inhibition constants (Ki) were 212 and 50 MUM, respectively. Molecular
      docking analyses with yeast and mammalian alpha-glucosidases revealed that
      compound 6 bind differently to these enzymes. Altogether, the results of this
      work suggest that preparations of V. corymbosa might delay glucose absorption in
      vivo. 

PMID- 26307963
TI  - The Influence of Sesquiterpenes from Myrica rubra on the Antiproliferative and
      Pro-Oxidative Effects of Doxorubicin and Its Accumulation in Cancer Cells.
AB  - The sesquiterpenes beta-caryophyllene, beta-caryophyllene oxide (CAO), alpha
      humulene (HUM), trans-nerolidol (NER), and valencene (VAL) are substantial
      components of the essential oil from Myrica rubra leaves which has exhibited
      significant antiproliferative effects in several intestinal cancer cell lines,
      with CaCo-2 cells being the most sensitive. The present study was designed to
      evaluate the effects of these sesquiterpenes on the efficacy and toxicity of the
      anticancer drug doxorubicin (DOX) in CaCo-2 cancer cells and in primary culture
      of rat hepatocytes. Our results showed that HUM, NER, VAL and CAO inhibited
      proliferation of CaCo-2 cancer cells but they did not affect the viability of
      hepatocytes. CAO, NER and VAL synergistically potentiated the efficacy of DOX in
      cancer cells killing. All sesquiterpenes exhibited the ability to selectively
      increase DOX accumulation in cancer cells and did not affect DOX concentration in
      hepatocytes. Additionally, CAO and VAL were able to increase the pro-oxidative
      effect of DOX in CaCo-2 cells. Moreover, CAO mildly ameliorated DOX toxicity in
      hepatocytes. Based on all results, CAO seems to be the most promising compound
      for further testing. 

PMID- 26307964
TI  - Inhibitory Effects of Amorphigenin on the Mitochondrial Complex I of Culex
      pipiens pallens Coquillett (Diptera: Culicidae).
AB  - Previous studies in our laboratory found that the extract from seeds of Amorpha
      fruticosa in the Leguminosae family had lethal effects against mosquito larvae,
      and an insecticidal compound amorphigenin was isolated. In this study, the
      inhibitory effects of amorphigenin against the mitochondrial complex I of Culex
      pipiens pallens (Diptera: Culicidae) were investigated and compared with that of
      rotenone. The results showed that amorphigenin and rotenone can decrease the
      mitochondrial complex I activity both in vivo and in vitro as the in vivo IC50
      values (the inhibitor concentrations leading to 50% of the enzyme activity lost)
      were determined to be 2.4329 and 2.5232 MUmol/L, respectively, while the in vitro
      IC50 values were 2.8592 and 3.1375 MUmol/L, respectively. Both amorphigenin and
      rotenone were shown to be reversible and mixed-I type inhibitors of the
      mitochondrial complex I of Cx. pipiens pallens, indicating that amorphigenin and
      rotenone inhibited the enzyme activity not only by binding with the free enzyme
      but also with the enzyme-substrate complex, and the values of KI and KIS for
      amorphigenin were determined to be 20.58 and 87.55 MUM, respectively, while the
      values for rotenone were 14.04 and 69.23 MUM, respectively. 

PMID- 26307965
TI  - Genome-Wide Identification and Expression Analyses of Aquaporin Gene Family
      during Development and Abiotic Stress in Banana.
AB  - Aquaporins (AQPs) function to selectively control the flow of water and other
      small molecules through biological membranes, playing crucial roles in various
      biological processes. However, little information is available on the AQP gene
      family in bananas. In this study, we identified 47 banana AQP genes based on the
      banana genome sequence. Evolutionary analysis of AQPs from banana, Arabidopsis,
      poplar, and rice indicated that banana AQPs (MaAQPs) were clustered into four
      subfamilies. Conserved motif analysis showed that all banana AQPs contained the
      typical AQP-like or major intrinsic protein (MIP) domain. Gene structure analysis
      suggested the majority of MaAQPs had two to four introns with a highly specific
      number and length for each subfamily. Expression analysis of MaAQP genes during
      fruit development and postharvest ripening showed that some MaAQP genes exhibited
      high expression levels during these stages, indicating the involvement of MaAQP
      genes in banana fruit development and ripening. Additionally, some MaAQP genes
      showed strong induction after stress treatment and therefore, may represent
      potential candidates for improving banana resistance to abiotic stress. Taken
      together, this study identified some excellent tissue-specific, fruit development
      and ripening-dependent, and abiotic stress-responsive candidate MaAQP genes,
      which could lay a solid foundation for genetic improvement of banana cultivars. 

PMID- 26307966
TI  - Polymer/Iron Oxide Nanoparticle Composites--A Straight Forward and Scalable
      Synthesis Approach.
AB  - Magnetic nanoparticle systems can be divided into single-core nanoparticles (with
      only one magnetic core per particle) and magnetic multi-core nanoparticles (with
      several magnetic cores per particle). Here, we report multi-core nanoparticle
      synthesis based on a controlled precipitation process within a well-defined oil
      in water emulsion to trap the superparamagnetic iron oxide nanoparticles (SPION)
      in a range of polymer matrices of choice, such as poly(styrene), poly(lactid
      acid), poly(methyl methacrylate), and poly(caprolactone). Multi-core particles
      were obtained within the Z-average size range of 130 to 340 nm. With the aim to
      combine the fast room temperature magnetic relaxation of small individual cores
      with high magnetization of the ensemble of SPIONs, we used small (<10 nm) core
      nanoparticles. The performed synthesis is highly flexible with respect to the
      choice of polymer and SPION loading and gives rise to multi-core particles with
      interesting magnetic properties and magnetic resonance imaging (MRI) contrast
      efficacy. 

PMID- 26307967
TI  - Magnetic Nanoparticle Arrays Self-Assembled on Perpendicular Magnetic Recording
      Media.
AB  - We study magnetic-field directed self-assembly of magnetic nanoparticles onto
      templates recorded on perpendicular magnetic recording media, and quantify
      feature width and height as a function of assembly time. Feature widths are
      determined from Scanning Electron Microscope (SEM) images, while heights are
      obtained with Atomic Force Microscopy (AFM). For short assembly times, widths
      were ~150 nm, while heights were ~14 nm, a single nanoparticle on average with a
      10:1 aspect ratio. For long assembly times, widths approach 550 nm, while the
      average height grows to 3 nanoparticles, ~35 nm; a 16:1 aspect ratio. We perform
      magnetometry on these self-assembled structures and observe the slope of the
      magnetic moment vs. field curve increases with time. This increase suggests
      magnetic nanoparticle interactions evolve from nanoparticle-nanoparticle
      interactions to cluster-cluster interactions as opposed to feature-feature
      interactions. We suggest the aspect ratio increase occurs because the magnetic
      field gradients are strongest near the transitions between recorded regions in
      perpendicular media. If these gradients can be optimized for assembly, strong
      potential exists for using perpendicular recording templates to assemble complex
      heterogeneous materials. 

PMID- 26307968
TI  - Endoplasmic Reticulum Stress Cooperates in Zearalenone-Induced Cell Death of RAW
      264.7 Macrophages.
AB  - Zearalenone (ZEA) is a fungal mycotoxin that causes cell apoptosis and necrosis.
      However, little is known about the molecular mechanisms of ZEA toxicity. The
      objective of this study was to explore the effects of ZEA on the proliferation
      and apoptosis of RAW 264.7 macrophages and to uncover the signaling pathway
      underlying the cytotoxicity of ZEA in RAW 264.7 macrophages. This study
      demonstrates that the endoplasmic reticulum (ER) stress pathway cooperated in ZEA
      induced cell death of the RAW 264.7 macrophages. Our results show that ZEA
      treatment reduced the viability of RAW 264.7 macrophages in a dose- and time
      dependent manner as shown by the 3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide assay (MTT) and flow cytometry assay. Western blots
      analysis revealed that ZEA increased the expression of glucose-regulated protein
      78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP), two ER
      stress-related marker genes. Furthermore, treating the cells with the ER stress
      inhibitors 4-phenylbutyrate (4-PBA) or knocking down CHOP, using lentivirus
      encoded short hairpin interfering RNAs (shRNAs), significantly diminished the ZEA
      induced increases in GRP78 and CHOP, and cell death. In summary, our results
      suggest that ZEA induces the apoptosis and necrosis of RAW 264.7 macrophages in a
      dose- and time-dependent manner via the ER stress pathway in which the activation
      of CHOP plays a critical role. 

PMID- 26307969
TI  - Effect of Factor XIII-A G185T Polymorphism on Visual Prognosis after Photodynamic
      Therapy for Neovascular Macular Degeneration.
AB  - Macular degenerations represent leading causes of central blindness or low vision
      in developed countries. Most of these severe visual disabilities are due to age
      related macular degeneration (AMD) and pathologic myopia (PM), both of which are
      frequently complicated by subfoveal choroidal neovascularization (CNV).
      Photodynamic therapy with verteporfin (PDT-V) is still employed for CNV treatment
      in selected cases or in combined regimen. In Caucasian patients, the common
      polymorphism G185T of factor XIII-A gene (FXIII-A-G185T; rs5985) has been
      described as predictor of poor angiographic CNV responsiveness to PDT-V.
      Nevertheless, the prognostic implications of this pharmacogenetic determinant on
      long-term visual outcome after a PDT-V regimen have not been evaluated. We
      retrospectively selected Caucasian patients presenting with treatment-naive CNV
      and receiving standardized PDT-V protocol for two years. The study population
      included patients affected by subfoveal CNV secondary to AMD or PM. We assessed
      the correlations between the polymorphic allele T of FXIII-A-G185T and: (1) total
      number of photodynamic treatments; and (2) change in visual acuity from baseline
      to the end of the follow-up period. Considering a total study population of 412
      patients with neovascular AMD or PM, the carriers of 185 T-allele of FXIII-A (GT
      or TT genotype) received a higher number of photodynamic treatments than patients
      without it (GG wild-type genotype) (p < 0.01; mean number of PDT-V: 5.51 vs.
      3.76, respectively). Moreover, patients with 185 T-allele of FXIII-A had a more
      marked worsening of visual acuity at 24 months than those with the GG-185 wild
      genotype (p < 0.01; mean difference in logMAR visual acuity: 0.22 vs. 0.08,
      respectively). The present findings show that the G185T polymorphism of the FXIII
      A gene is associated with significant differences in the long-term therapeutic
      outcomes of patients treated with standardized PDT-V protocol. The comprehensive
      appraisal of both anti-thrombophilic effects due to FXIII-A G185T variant and
      photo-thrombotic action of PDT-V toward CNV provides several clues about the
      rationale of this intriguing pharmacogenetic correlation. Further investigations
      are warranted to outline the appropriate paradigm for guiding PDT-V utilization
      in the course of the combined therapeutic protocol for neovascular macular
      degeneration. 

PMID- 26307970
TI  - In Silico Analysis of Correlations between Protein Disorder and Post
      Translational Modifications in Algae.
AB  - Recent proteome analyses have reported that intrinsically disordered regions
      (IDRs) of proteins play important roles in biological processes. In higher plants
      whose genomes have been sequenced, the correlation between IDRs and post
      translational modifications (PTMs) has been reported. The genomes of various
      eukaryotic algae as common ancestors of plants have also been sequenced. However,
      no analysis of the relationship to protein properties such as structure and PTMs
      in algae has been reported. Here, we describe correlations between IDR content
      and the number of PTM sites for phosphorylation, glycosylation, and
      ubiquitination, and between IDR content and regions rich in proline, glutamic
      acid, serine, and threonine (PEST) and transmembrane helices in the sequences of
      20 algae proteomes. Phosphorylation, O-glycosylation, ubiquitination, and PEST
      preferentially occurred in disordered regions. In contrast, transmembrane helices
      were favored in ordered regions. N-glycosylation tended to occur in ordered
      regions in most of the studied algae; however, it correlated positively with
      disordered protein content in diatoms. Additionally, we observed that disordered
      protein content and the number of PTM sites were significantly increased in the
      species-specific protein clusters compared to common protein clusters among the
      algae. Moreover, there were specific relationships between IDRs and PTMs among
      the algae from different groups. 

PMID- 26307971
TI  - Mitochondrial Transcription Factor A and Mitochondrial Genome as Molecular
      Targets for Cisplatin-Based Cancer Chemotherapy.
AB  - Mitochondria are important cellular organelles that function as control centers
      of the energy supply for highly proliferative cancer cells and regulate apoptosis
      after cancer chemotherapy. Cisplatin is one of the most important
      chemotherapeutic agents and a key drug in therapeutic regimens for a broad range
      of solid tumors. Cisplatin may directly interact with mitochondria, which can
      induce apoptosis. The direct interactions between cisplatin and mitochondria may
      account for our understanding of the clinical activity of cisplatin and
      development of resistance. However, the basis for the roles of mitochondria under
      treatment with chemotherapy is poorly understood. In this review, we present
      novel aspects regarding the unique characteristics of the mitochondrial genome in
      relation to the use of platinum-based chemotherapy and describe our recent work
      demonstrating the importance of the mitochondrial transcription factor A (mtTFA)
      expression in cancer cells. 

PMID- 26307972
TI  - Curcumol Inhibits Growth and Induces Apoptosis of Colorectal Cancer LoVo Cell
      Line via IGF-1R and p38 MAPK Pathway.
AB  - Curcumol, isolated from the traditional medical plant Rhizoma Curcumae, is the
      bioactive component of Zedoary oil, whose potential anti-tumor effect has
      attracted considerable attention in recent years. Though many researchers have
      reported curcumol and its bioactivity, the potential molecular mechanism for its
      anti-cancer effect in colorectal cancer LoVo cells still remains unclear. In the
      present study, we found that curcumol showed growth inhibition and induced
      apoptosis of LoVo cells in a dose- and time-dependent manner. The occurrence of
      its proliferation inhibition and apoptosis came with suppression of IGF-1R
      expression, and then increased the phosphorylation of p38 mitogen activated
      protein kinase (MAPK), which might result in a cascade response by inhibiting the
      CREB survival pathway and finally triggered Bax/Bcl-2 and poly(ADP-ribose)
      polymerase 1 (PARP-1) apoptosis signals. Moreover, curcumol inhibited colorectal
      cancer in xenograft models of nude mice. Immunohistochemical and Western blot
      analysis revealed that curcumol could decrease the expression of ki-67, Bcl-2 as
      well as CREB1, and increase the expression of Bax and the phosphorylation of p38,
      which were consistent with our in vitro study. Overall, our in vitro and in vivo
      data confirmed the anti-cancer activity of curcumol, which was related to a
      significant inhibition of IGF-1R and activation of p38 MAPKs, indicating that
      curcumol may be a potential anti-tumor agent for colorectal carcinoma therapy. 

PMID- 26307973
TI  - Accurate Ab Initio and Template-Based Prediction of Short Intrinsically
      Disordered Regions by Bidirectional Recurrent Neural Networks Trained on Large
      Scale Datasets.
AB  - Intrinsically-disordered regions lack a well-defined 3D structure, but play key
      roles in determining the function of many proteins. Although predictors of
      disorder have been shown to achieve relatively high rates of correct
      classification of these segments, improvements over the the years have been slow,
      and accurate methods are needed that are capable of accommodating the ever
      increasing amount of structurally-determined protein sequences to try to boost
      predictive performances. In this paper, we propose a predictor for short
      disordered regions based on bidirectional recurrent neural networks and tested by
      rigorous five-fold cross-validation on a large, non-redundant dataset collected
      from MobiDB, a new comprehensive source of protein disorder annotations. The
      system exploits sequence and structural information in the forms of frequency
      profiles, predicted secondary structure and solvent accessibility and direct
      disorder annotations from homologous protein structures (templates) deposited in
      the Protein Data Bank. The contributions of sequence, structure and homology
      information result in large improvements in predictive accuracy. Additionally,
      the large scale of the training set leads to low false positive rates, making our
      systems a robust and efficient way to address high-throughput disorder
      prediction. 

PMID- 26307975
TI  - Selection and Characterization of Single Chain Antibody Fragments Specific for
      Hsp90 as a Potential Cancer Targeting Molecule.
AB  - Heat shock proteins play an essential role in facilitating malignant
      transformation and they have been recognized as important factors in human
      cancers. One of the key elements of the molecular chaperones machinery is Hsp90
      and it has recently become a target for anticancer therapeutic approaches. The
      potential and importance of Hsp90-directed agents becomes apparent when one
      realizes that disruption of Hsp90 function may influence over 200 oncogenic
      client proteins. Here, we described the selection and characterization of Hsp90
      specific antibody fragments from commercially available Tomlinson I and J phage
      display libraries. The affinities of Hsp90-binding scFv variants were measured
      using SPR method. Then, based on the best clone selected, we performed the
      affinity maturation procedure and obtained valuable Hsp90-specific clones. The
      selected binders were expressed and applied for immunostaining, ELISA and SPR
      analysis using model cancer cell lines. All performed experiments confirmed the
      ability of selected antibodies to interact with the Hsp90. Therefore, the
      presented Hsp90-specific scFv, might be a starting point for the development of a
      novel antibody-based strategy targeting cancer. 

PMID- 26307974
TI  - Regulatory Roles of Non-Coding RNAs in Colorectal Cancer.
AB  - Non-coding RNAs (ncRNAs) have recently gained attention because of their
      involvement in different biological processes. An increasing number of studies
      have demonstrated that mutations or abnormal expression of ncRNAs are closely
      associated with various diseases including cancer. The present review is a
      comprehensive examination of the aberrant regulation of ncRNAs in colorectal
      cancer (CRC) and a summary of the current findings on ncRNAs, including long
      ncRNAs, microRNAs, small interfering RNAs, small nucleolar RNAs, small nuclear
      RNAs, Piwi-interacting RNAs, and circular RNAs. These ncRNAs might become novel
      biomarkers and targets as well as potential therapeutic tools for the treatment
      of CRC in the near future and this review may provide important clues for further
      research on CRC and for the selection of effective therapeutic targets. 

PMID- 26307976
TI  - Resolving Intra- and Inter-Molecular Structure with Non-Contact Atomic Force
      Microscopy.
AB  - A major challenge in molecular investigations at surfaces has been to image
      individual molecules, and the assemblies they form, with single-bond resolution.
      Scanning probe microscopy, with its exceptionally high resolution, is ideally
      suited to this goal. With the introduction of methods exploiting molecularly
      terminated tips, where the apex of the probe is, for example, terminated with a
      single CO, Xe or H2 molecule, scanning probe methods can now achieve higher
      resolution than ever before. In this review, some of the landmark results related
      to attaining intramolecular resolution with non-contact atomic force microscopy
      (NC-AFM) are summarised before focussing on recent reports probing molecular
      assemblies where apparent intermolecular features have been observed. Several
      groups have now highlighted the critical role that flexure in the tip-sample
      junction plays in producing the exceptionally sharp images of both intra- and
      apparent inter-molecular structure. In the latter case, the features have been
      identified as imaging artefacts, rather than real intermolecular bonds. This
      review discusses the potential for NC-AFM to provide exceptional resolution of
      supramolecular assemblies stabilised via a variety of intermolecular forces and
      highlights the potential challenges and pitfalls involved in interpreting bonding
      interactions. 

PMID- 26307977
TI  - Inhibition of NF-kappaB in Tumor Cells Exacerbates Immune Cell Activation
      Following Photodynamic Therapy.
AB  - Although photodynamic therapy (PDT) yields very good outcomes in numerous types
      of superficial solid cancers, some tumors respond suboptimally to PDT. Novel
      treatment strategies are therefore needed to enhance the efficacy in these
      therapy-resistant tumors. One of these strategies is to combine PDT with
      inhibitors of PDT-induced survival pathways. In this respect, the transcription
      factor nuclear factor kappaB (NF-kappaB) has been identified as a potential
      pharmacological target, albeit inhibition of NF-kappaB may concurrently dampen
      the subsequent anti-tumor immune response required for complete tumor eradication
      and abscopal effects. In contrast to these postulations, this study demonstrated
      that siRNA knockdown of NF-kappaB in murine breast carcinoma (EMT-6) cells
      increased survival signaling in these cells and exacerbated the inflammatory
      response in murine RAW 264.7 macrophages. These results suggest a pro-death and
      immunosuppressive role of NF-kappaB in PDT-treated cells that concurs with a
      hyperstimulated immune response in innate immune cells. 

PMID- 26307978
TI  - Atherosclerotic Calcification Detection: A Comparative Study of Carotid
      Ultrasound and Cone Beam CT.
AB  - BACKGROUND AND AIM: Arterial calcification is often detected on ultrasound
      examination but its diagnostic accuracy is not well validated. The aim of this
      study was to determine the accuracy of carotid ultrasound B mode findings in
      detecting atherosclerotic calcification quantified by cone beam computed
      tomography (CBCT). METHODS: We analyzed 94 carotid arteries, from 88 patients
      (mean age 70 +/- 7 years, 33% females), who underwent pre-endarterectomy
      ultrasound examination. Plaques with high echogenic nodules and posterior
      shadowing were considered calcified. After surgery, the excised plaques were
      examined using CBCT, from which the calcification volume (mm3) was calculated. In
      cases with multiple calcifications the largest calcification nodule volume was
      used to represent the plaque. Carotid artery calcification by the two imaging
      techniques was compared using conventional correlations. RESULTS: Carotid
      ultrasound was highly accurate in detecting the presence of calcification; with a
      sensitivity of 88.2%. Based on the quartile ranges of calcification volumes
      measured by CBCT we have divided plaque calcification into four groups: <8; 8-35;
      36-70 and >70 mm3. Calcification volumes >=8 were accurately detectable by
      ultrasound with a sensitivity of 96%. Of the 21 plaques with <8 mm3 calcification
      volume; only 13 were detected by ultrasound; resulting in a sensitivity of 62%.
      There was no difference in the volume of calcification between symptomatic and
      asymptomatic patients. CONCLUSION: Carotid ultrasound is highly accurate in
      detecting the presence of calcified atherosclerotic lesions of volume >=8 mm3;
      but less accurate in detecting smaller volume calcified plaques. Further
      development of ultrasound techniques should allow better detection of early
      arterial calcification.

PMID- 26307979
TI  - Docosahexaenoic Acid Levels in Blood and Metabolic Syndrome in Obese Children: Is
      There a Link?
AB  - Prevalence of metabolic syndrome is increasing in the pediatric population.
      Considering the different existing criteria to define metabolic syndrome, the use
      of the International Diabetes Federation (IDF) criteria has been suggested in
      children. Docosahexaenoic acid (DHA) has been associated with beneficial effects
      on health. The evidence about the relationship of DHA status in blood and
      components of the metabolic syndrome is unclear. This review discusses the
      possible association between DHA content in plasma and erythrocytes and
      components of the metabolic syndrome included in the IDF criteria (obesity,
      alteration of glucose metabolism, blood lipid profile, and blood pressure) and
      non-alcoholic fatty liver disease in obese children. The current evidence is
      inconsistent and no definitive conclusion can be drawn in the pediatric
      population. Well-designed longitudinal and powered trials need to clarify the
      possible association between blood DHA status and metabolic syndrome. 

PMID- 26307980
TI  - Exploiting Size-Dependent Drag and Magnetic Forces for Size-Specific Separation
      of Magnetic Nanoparticles.
AB  - Realizing the full potential of magnetic nanoparticles (MNPs) in nanomedicine
      requires the optimization of their physical and chemical properties. Elucidation
      of the effects of these properties on clinical diagnostic or therapeutic
      properties, however, requires the synthesis or purification of homogenous
      samples, which has proved to be difficult. While initial simulations indicated
      that size-selective separation could be achieved by flowing magnetic
      nanoparticles through a magnetic field, subsequent in vitro experiments were
      unable to reproduce the predicted results. Magnetic field-flow fractionation,
      however, was found to be an effective method for the separation of polydisperse
      suspensions of iron oxide nanoparticles with diameters greater than 20 nm. While
      similar methods have been used to separate magnetic nanoparticles before, no
      previous work has been done with magnetic nanoparticles between 20 and 200 nm.
      Both transmission electron microscopy (TEM) and dynamic light scattering (DLS)
      analysis were used to confirm the size of the MNPs. Further development of this
      work could lead to MNPs with the narrow size distributions necessary for their in
      vitro and in vivo optimization.

PMID- 26307981
TI  - AGEs-Induced IL-6 Synthesis Precedes RAGE Up-Regulation in HEK 293 Cells: An
      Alternative Inflammatory Mechanism?
AB  - Advanced glycation end products (AGEs) can activate the inflammatory pathways
      involved in diabetic nephropathy. Understanding these molecular pathways could
      contribute to therapeutic strategies for diabetes complications. We evaluated the
      modulation of inflammatory and oxidative markers, as well as the protective
      mechanisms employed by human embryonic kidney cells (HEK 293) upon exposure to
      200 MUg/mL bovine serum albumine (BSA) or AGEs-BSA for 12, 24 and 48 h. The mRNA
      and protein expression levels of AGEs receptor (RAGE) and heat shock proteins
      (HSPs) 27, 60 and 70, the activity of antioxidant enzymes and the expression
      levels of eight cytokines were analysed. Cell damage via oxidative mechanisms was
      evaluated by glutathione and malondialdehyde levels. The data revealed two
      different time scale responses. First, the up-regulation of interleukin-6 (IL-6),
      HSP 27 and high catalase activity were detected as early as 12 h after exposure
      to AGEs-BSA, while the second response, after 24 h, consisted of NF-kappaB p65,
      RAGE, HSP 70 and inflammatory cytokine up-regulation, glutathione depletion,
      malondialdehyde increase and the activation of antioxidant enzymes. IL-6 might be
      important in the early ignition of inflammatory responses, while the cellular
      redox imbalance, RAGE activation and NF-kappaB p65 increased expression further
      enhance inflammatory signals in HEK 293 cells. 

PMID- 26307983
TI  - Huge Inverse Magnetization Generated by Faraday Induction in Nano-Sized Au@Ni
      Core@Shell Nanoparticles.
AB  - We report on the design and observation of huge inverse magnetizations pointing
      in the direction opposite to the applied magnetic field, induced in nano-sized
      amorphous Ni shells deposited on crystalline Au nanoparticles by turning the
      applied magnetic field off. The magnitude of the induced inverse magnetization is
      very sensitive to the field reduction rate as well as to the thermal and field
      processes before turning the magnetic field off, and can be as high as 54% of the
      magnetization prior to cutting off the applied magnetic field. Memory effect of
      the induced inverse magnetization is clearly revealed in the relaxation
      measurements. The relaxation of the inverse magnetization can be described by an
      exponential decay profile, with a critical exponent that can be effectively tuned
      by the wait time right after reaching the designated temperature and before the
      applied magnetic field is turned off. The key to these effects is to have the
      induced eddy current running beneath the amorphous Ni shells through Faraday
      induction. 

PMID- 26307982
TI  - Insight into the Structural Determinants of Imidazole Scaffold-Based Derivatives
      as TNF-alpha Release Inhibitors by in Silico Explorations.
AB  - Presently, 151 widely-diverse pyridinylimidazole-based compounds that show
      inhibitory activities at the TNF-alpha release were investigated. By using the
      distance comparison technique (DISCOtech), comparative molecular field analysis
      (CoMFA), and comparative molecular similarity index analysis (CoMSIA) methods,
      the pharmacophore models and the three-dimensional quantitative structure
      activity relationships (3D-QSAR) of the compounds were explored. The proposed
      pharmacophore model, including two hydrophobic sites, two aromatic centers, two H
      bond donor atoms, two H-bond acceptor atoms, and two H-bond donor sites
      characterizes the necessary structural features of TNF-alpha release inhibitors.
      Both the resultant CoMFA and CoMSIA models exhibited satisfactory predictability
      (with Q(2) (cross-validated correlation coefficient) = 0.557, R(2)ncv (non-cross
      validated correlation coefficient) = 0.740, R(2)pre (predicted correlation
      coefficient) = 0.749 and Q(2) = 0.598, R(2)ncv = 0.767, R(2)pre = 0.860,
      respectively). Good consistency was observed between the 3D-QSAR models and the
      pharmacophore model that the hydrophobic interaction and hydrogen bonds play
      crucial roles in the mechanism of actions. The corresponding contour maps
      generated by these models provide more diverse information about the key
      intermolecular interactions of inhibitors with the surrounding environment. All
      these models have extended the understanding of imidazole-based compounds in the
      structure-activity relationship, and are useful for rational design and screening
      of novel 2-thioimidazole-based TNF-alpha release inhibitors. 

PMID- 26307984
TI  - Avoidance and Potential Remedy Solutions of Chimeras in Reconstructing the
      Phylogeny of Aphids Using the 16S rRNA Gene of Buchnera: A Case in Lachninae
      (Hemiptera).
AB  - It is known that PCR amplification of highly homologous genes from complex DNA
      mixtures can generate a significant proportion of chimeric sequences. The 16S
      rRNA gene is not only widely used in estimating the species diversity of
      endosymbionts in aphids but also used to explore the co-diversification of aphids
      and their endosymbionts. Thus, chimeric sequences may lead to the discovery of
      non-existent endosymbiont species and mislead Buchnera-based phylogenetic
      analysis that lead to false conclusions. In this study, a high probability
      (6.49%) of chimeric sequence occurrence was found in the amplified 16S rRNA gene
      sequences of endosymbionts from aphid species in the subfamily Lachninae. These
      chimeras are hybrid products of multiple parent sequences from the dominant
      species of endosymbionts in each corresponding host. It is difficult to identify
      the chimeric sequences of a new or unidentified species due to the high
      variability of their main parent, Buchnera aphidicola, and because the chimeric
      sequences can confuse the phylogenetic analysis of 16S rRNA gene sequences. These
      chimeras present a challenge to Buchnera-based phylogenetic research in aphids.
      Thus, our study strongly suggests that using appropriate methods to detect
      chimeric 16S rRNA sequences may avoid some false conclusions in endosymbiont
      based aphid research.

PMID- 26307985
TI  - Impact of Single Nucleotide Polymorphisms (SNPs) on Immunosuppressive Therapy in
      Lung Transplantation.
AB  - Lung transplant patients present important variability in immunosuppressant blood
      concentrations during the first months after transplantation. Pharmacogenetics
      could explain part of this interindividual variability. We evaluated SNPs in
      genes that have previously shown correlations in other kinds of solid organ
      transplantation, namely ABCB1 and CYP3A5 genes with tacrolimus (Tac) and ABCC2,
      UGT1A9 and SLCO1B1 genes with mycophenolic acid (MPA), during the first six
      months after lung transplantation (51 patients). The genotype was correlated to
      the trough blood drug concentrations corrected for dose and body weight (C0/Dc).
      The ABCB1 variant in rs1045642 was associated with significantly higher Tac
      concentration, at six months post-transplantation (CT vs. CC). In the MPA
      analysis, CT patients in ABCC2 rs3740066 presented significantly lower blood
      concentrations than CC or TT, three months after transplantation. Other
      tendencies, confirming previously expected results, were found associated with
      the rest of studied SNPs. An interesting trend was recorded for the incidence of
      acute rejection according to NOD2/CARD15 rs2066844 (CT: 27.9%; CC: 12.5%).
      Relevant SNPs related to Tac and MPA in other solid organ transplants also seem
      to be related to the efficacy and safety of treatment in the complex setting of
      lung transplantation. 

PMID- 26307986
TI  - DNA-Redox Cation Interaction Improves the Sensitivity of an Electrochemical
      Immunosensor for Protein Detection.
AB  - A simple DNA-redox cation interaction enhancement strategy has been developed to
      improve the sensitivity of electrochemical immunosensors for protein detection.
      Instead of labeling with fluorophores or redox-active groups, the detection
      antibodies were tethered with DNA single strands. Based on the electrostatic
      interaction between redox cations ([Ru(NH3)6](3+)) and negatively charged DNA
      backbone, enhanced electrochemical signals were obtained. Human chorionic
      gonadotropin (hCG) detection has been performed as a trial analysis. A linear
      response range up to the concentration of 25 mIU/mL and a detection limit of 1.25
      mIU/mL have been achieved, both are comparable with the ultrasensitive enzyme
      linked immunosorbent assay (ELISA) tests. The method also shows great selectivity
      towards hCG over other hormones such as thyroid stimulating hormone (TSH) and
      follicle stimulating hormone (FSH). By and large, our approach bears the merits
      of cost effectiveness and simplicity of instrumentation in comparison with
      conventional optical detection methods. 

PMID- 26307987
TI  - The Thermoluminescence Response of Ge-Doped Flat Fibers to Gamma Radiation.
AB  - Study has been undertaken of the thermoluminescence (TL) yield of various tailor
      made flat cross-section 6 mol% Ge-doped silica fibers, differing only in respect
      of external dimensions. Key TL dosimetric characteristics have been investigated,
      including glow curves, dose response, sensitivity, fading and reproducibility.
      Using a (60)Co source, the samples were irradiated to doses within the range 1 to
      10 Gy. Prior to irradiation, the flat fibers were sectioned into 6 mm lengths,
      weighed, and annealed at 400  degrees C for 1 h. TL readout was by means of a
      Harshaw Model 3500 TLD reader, with TLD-100 chips (LiF:Mg, Ti) used as a
      reference dosimeter to allow the relative response of the fibers to be evaluated.
      The fibers have been found to provide highly linear dose response and excellent
      reproducibility over the range of doses investigated, demonstrating high
      potential as TL-mode detectors in radiation medicine applications. Mass for mass,
      the results show the greatest TL yield to be provided by fibers of the smallest
      cross-section, analysis indicating this to be due to minimal light loss in
      transport of the TL through the bulk of the silica medium. 

PMID- 26307988
TI  - Context Aware Middleware Architectures: Survey and Challenges.
AB  - Context aware applications, which can adapt their behaviors to changing
      environments, are attracting more and more attention. To simplify the complexity
      of developing applications, context aware middleware, which introduces context
      awareness into the traditional middleware, is highlighted to provide a
      homogeneous interface involving generic context management solutions. This paper
      provides a survey of state-of-the-art context aware middleware architectures
      proposed during the period from 2009 through 2015. First, a preliminary
      background, such as the principles of context, context awareness, context
      modelling, and context reasoning, is provided for a comprehensive understanding
      of context aware middleware. On this basis, an overview of eleven carefully
      selected middleware architectures is presented and their main features explained.
      Then, thorough comparisons and analysis of the presented middleware architectures
      are performed based on technical parameters including architectural style,
      context abstraction, context reasoning, scalability, fault tolerance,
      interoperability, service discovery, storage, security & privacy, context
      awareness level, and cloud-based big data analytics. The analysis shows that
      there is actually no context aware middleware architecture that complies with all
      requirements. Finally, challenges are pointed out as open issues for future work.

PMID- 26307989
TI  - Model-Based Design of Tree WSNs for Decentralized Detection.
AB  - The classical decentralized detection problem of finding the optimal decision
      rules at the sensor and fusion center, as well as variants that introduce
      physical channel impairments have been studied extensively in the literature. The
      deployment of WSNs in decentralized detection applications brings new challenges
      to the field. Protocols for different communication layers have to be co-designed
      to optimize the detection performance. In this paper, we consider the
      communication network design problem for a tree WSN. We pursue a system-level
      approach where a complete model for the system is developed that captures the
      interactions between different layers, as well as different sensor quality
      measures. For network optimization, we propose a hierarchical optimization
      algorithm that lends itself to the tree structure, requiring only local network
      information. The proposed design approach shows superior performance over several
      contentionless and contention-based network design approaches. 

PMID- 26307990
TI  - Highly Sensitive Electrochemical Determination of Alfatoxin B1 Using Quantum Dots
      Assembled Amplification Labels.
AB  - A competitive electrochemical immunoassay for highly sensitive detection of AFB1
      is demonstrated using layer-by-layer (LBL) assembled quantum dots (QDs) as
      labels. To investigate the effects of the higher sensitivity of square wave
      voltammetric stripping (SWV) and of the LBL technique on the proposed
      immunoassays, the proposed assay was compared to electrochemical (EC) and
      fluorescent immunoassays, which did not use LBL technology. Peanut samples were
      analyzed using the three immunoassays. The limits of detection (LODs) were 0.018,
      0.046 and 0.212 ng/mL, respectively, while the sensitivities were 0.308, 1.011
      and 4.594 ng/mL, respectively. The proposed electrochemical immunoassay displayed
      a significant improvement in sensitivity, thereby providing a simple and
      sensitive alternative strategy for determining AFB1 levels in peanut samples. 

PMID- 26307991
TI  - Ultrahigh-Temperature Regeneration of Long Period Gratings (LPGs) in Boron
      Codoped Germanosilicate Optical Fibre.
AB  - The regeneration of UV-written long period gratings (LPG) in boron-codoped
      germanosilicate "W" fibre is demonstrated and studied. They survive temperatures
      over 1000  degrees C. Compared with regenerated FBGs fabricated in the same type
      of fibre, the evolution curves of LPGs during regeneration and post-annealing
      reveal even more detail of glass relaxation. Piece-wise temperature dependence is
      observed, indicating the onset of a phase transition of glass in the core and
      inner cladding at ~500  degrees C and ~250  degrees C, and the melting of inner
      cladding between 860  degrees C and 900  degrees C. An asymmetric spectral
      response with increasing and decreasing annealing temperature points to the
      complex process dependent material system response. Resonant wavelength tuning by
      adjusting the dwell temperature at which regeneration is undertaken is
      demonstrated, showing a shorter resonant wavelength and shorter time for
      stabilisation with higher dwell temperatures. All the regenerated LPGs are nearly
      strain-insensitive and cannot be tuned by applying loads during annealing as done
      for regenerated FBGs. 

PMID- 26307992
TI  - Research and Experiments on a Unipolar Capacitive Voltage Sensor.
AB  - Voltage sensors are an important part of the electric system. In service,
      traditional voltage sensors need to directly contact a high-voltage charged body.
      Sensors involve a large volume, complex insulation structures, and high design
      costs. Typically an iron core structure is adopted. As a result, ferromagnetic
      resonance can occur easily during practical application. Moreover, owing to the
      multilevel capacitor divider, the sensor cannot reflect the changes of measured
      voltage in time. Based on the electric field coupling principle, this paper
      designs a new voltage sensor; the unipolar structure design solves many problems
      of traditional voltage sensors like the great insulation design difficulty and
      high costs caused by grounding electrodes. A differential signal input structure
      is adopted for the detection circuit, which effectively restrains the influence
      of the common-mode interference signal. Through sensor modeling, simulation and
      calculations, the structural design of the sensor electrode was optimized,
      miniaturization of the sensor was realized, the voltage division ratio of the
      sensor was enhanced, and the phase difference of sensor measurement was weakened.
      The voltage sensor is applied to a single-phase voltage class line of 10 kV for
      testing. According to the test results, the designed sensor is able to meet the
      requirements of accurate and real-time measurement for voltage of the charged
      conductor as well as to provide a new method for electricity larceny prevention
      and on-line monitoring of the power grid in an electric system. Therefore, it can
      satisfy the development demands of the smart power grid. 

PMID- 26307993
TI  - Evaluation of the Fourier Frequency Spectrum Peaks of Milk Electrical
      Conductivity Signals as Indexes to Monitor the Dairy Goats' Health Status by On
      Line Sensors.
AB  - The aim of this study is a further characterization of the electrical
      conductivity (EC) signal of goat milk, acquired on-line by EC sensors, to
      identify new indexes representative of the EC variations that can be observed
      during milking, when considering not healthy (NH) glands. Two foremilk gland
      samples from 42 Saanen goats, were collected for three consecutive weeks and for
      three different lactation stages (LS: 0-60 Days In Milking (DIM); 61-120 DIM; 121
      180 DIM), for a total amount of 1512 samples. Bacteriological analyses and
      somatic cells counts (SCC) were used to define the health status of the glands.
      With negative bacteriological analyses and SCC < 1,000,000 cells/mL, glands were
      classified as healthy. When bacteriological analyses were positive or showed a
      SCC > 1,000,000 cells/mL, glands were classified as NH. For each milk EC signal,
      acquired on-line and for each gland considered, the Fourier frequency spectrum of
      the signal was calculated and three representative frequency peaks were
      identified. To evaluate data acquired a MIXED procedure was used considering the
      HS, LS and LS * HS as explanatory variables in the statistical model.Results
      showed that the studied frequency peaks had a significant relationship with the
      gland's health status. Results also explained how the milk EC signals' pattern
      change in case of NH glands. In fact, it is characterized by slower fluctuations
      (due to the lower frequencies of the peaks) and by an irregular trend (due to the
      higher amplitudes of all the main frequency peaks). Therefore, these frequency
      peaks could be used as new indexes to improve the performances of algorithms
      based on multivariate models which evaluate the health status of dairy goats
      through the use of gland milk EC sensors. 

PMID- 26307994
TI  - Low Power Wireless Smoke Alarm System in Home Fires.
AB  - A novel sensing device for fire detection in domestic environments is presented.
      The fire detector uses a combination of several sensors that not only detect
      smoke, but discriminate between different types of smoke. This feature avoids
      false alarms and warns of different situations. Power consumption is optimized
      both in terms of hardware and software, providing a high degree of autonomy of
      almost five years. Data gathered from the device are transmitted through a
      wireless communication to a base station. The low cost and compact design
      provides wide application prospects. 

PMID- 26307995
TI  - ECG Sensor Card with Evolving RBP Algorithms for Human Verification.
AB  - It is known that cardiac and respiratory rhythms in electrocardiograms (ECGs) are
      highly nonlinear and non-stationary. As a result, most traditional time-domain
      algorithms are inadequate for characterizing the complex dynamics of the ECG.
      This paper proposes a new ECG sensor card and a statistical-based ECG algorithm,
      with the aid of a reduced binary pattern (RBP), with the aim of achieving faster
      ECG human identity recognition with high accuracy. The proposed algorithm has one
      advantage that previous ECG algorithms lack-the waveform complex information and
      de-noising preprocessing can be bypassed; therefore, it is more suitable for non
      stationary ECG signals. Experimental results tested on two public ECG databases
      (MIT-BIH) from MIT University confirm that the proposed scheme is feasible with
      excellent accuracy, low complexity, and speedy processing. To be more specific,
      the advanced RBP algorithm achieves high accuracy in human identity recognition
      and is executed at least nine times faster than previous algorithms. Moreover,
      based on the test results from a long-term ECG database, the evolving RBP
      algorithm also demonstrates superior capability in handling long-term and non
      stationary ECG signals. 

PMID- 26307996
TI  - High-Performance Motion Estimation for Image Sensors with Video Compression.
AB  - It is important to reduce the time cost of video compression for image sensors in
      video sensor network. Motion estimation (ME) is the most time-consuming part in
      video compression. Previous work on ME exploited intra-frame data reuse in a
      reference frame to improve the time efficiency but neglected inter-frame data
      reuse. We propose a novel inter-frame data reuse scheme which can exploit both
      intra-frame and inter-frame data reuse for ME in video compression (VC-ME).
      Pixels of reconstructed frames are kept on-chip until they are used by the next
      current frame to avoid off-chip memory access. On-chip buffers with smart
      schedules of data access are designed to perform the new data reuse scheme. Three
      levels of the proposed inter-frame data reuse scheme are presented and analyzed.
      They give different choices with tradeoff between off-chip bandwidth requirement
      and on-chip memory size. All three levels have better data reuse efficiency than
      their intra-frame counterparts, so off-chip memory traffic is reduced
      effectively. Comparing the new inter-frame data reuse scheme with the traditional
      intra-frame data reuse scheme, the memory traffic can be reduced by 50% for VC
      ME. 

PMID- 26307997
TI  - GPS/DR Error Estimation for Autonomous Vehicle Localization.
AB  - Autonomous vehicles require highly reliable navigation capabilities. For example,
      a lane-following method cannot be applied in an intersection without lanes, and
      since typical lane detection is performed using a straight-line model, errors can
      occur when the lateral distance is estimated in curved sections due to a model
      mismatch. Therefore, this paper proposes a localization method that uses GPS/DR
      error estimation based on a lane detection method with curved lane models, stop
      line detection, and curve matching in order to improve the performance during
      waypoint following procedures. The advantage of using the proposed method is that
      position information can be provided for autonomous driving through
      intersections, in sections with sharp curves, and in curved sections following a
      straight section. The proposed method was applied in autonomous vehicles at an
      experimental site to evaluate its performance, and the results indicate that the
      positioning achieved accuracy at the sub-meter level. 

PMID- 26307998
TI  - Towards a Low-Cost Remote Memory Attestation for the Smart Grid.
AB  - In the smart grid, measurement devices may be compromised by adversaries, and
      their operations could be disrupted by attacks. A number of schemes to
      efficiently and accurately detect these compromised devices remotely have been
      proposed. Nonetheless, most of the existing schemes detecting compromised devices
      depend on the incremental response time in the attestation process, which are
      sensitive to data transmission delay and lead to high computation and network
      overhead. To address the issue, in this paper, we propose a low-cost remote
      memory attestation scheme (LRMA), which can efficiently and accurately detect
      compromised smart meters considering real-time network delay and achieve low
      computation and network overhead. In LRMA, the impact of real-time network delay
      on detecting compromised nodes can be eliminated via investigating the time
      differences reported from relay nodes. Furthermore, the attestation frequency in
      LRMA is dynamically adjusted with the compromised probability of each node, and
      then, the total number of attestations could be reduced while low computation and
      network overhead can be achieved. Through a combination of extensive theoretical
      analysis and evaluations, our data demonstrate that our proposed scheme can
      achieve better detection capacity and lower computation and network overhead in
      comparison to existing schemes. 

PMID- 26307999
TI  - Efficient Implementation of a Symbol Timing Estimator for Broadband PLC.
AB  - Broadband Power Line Communications (PLC) have taken advantage of the research
      advances in multi-carrier modulations to mitigate frequency selective fading, and
      their adoption opens up a myriad of applications in the field of sensory and
      automation systems, multimedia connectivity or smart spaces. Nonetheless, the use
      of these multi-carrier modulations, such as Wavelet-OFDM, requires a highly
      accurate symbol timing estimation for reliably recovering of transmitted data.
      Furthermore, the PLC channel presents some particularities that prevent the
      direct use of previous synchronization algorithms proposed in wireless
      communication systems. Therefore more research effort should be involved in the
      design and implementation of novel and robust synchronization algorithms for PLC,
      thus enabling real-time synchronization. This paper proposes a symbol timing
      estimator for broadband PLC based on cross-correlation with multilevel
      complementary sequences or Zadoff-Chu sequences and its efficient implementation
      in a FPGA; the obtained results show a 90% of success rate in symbol timing
      estimation for a certain PLC channel model and a reduced resource consumption for
      its implementation in a Xilinx Kyntex FPGA. 

PMID- 26308000
TI  - Distance-Dependent Multimodal Image Registration for Agriculture Tasks.
AB  - Image registration is the process of aligning two or more images of the same
      scene taken at different times; from different viewpoints; and/or by different
      sensors. This research focuses on developing a practical method for automatic
      image registration for agricultural systems that use multimodal sensory systems
      and operate in natural environments. While not limited to any particular
      modalities; here we focus on systems with visual and thermal sensory inputs. Our
      approach is based on pre-calibrating a distance-dependent transformation matrix
      (DDTM) between the sensors; and representing it in a compact way by regressing
      the distance-dependent coefficients as distance-dependent functions. The DDTM is
      measured by calculating a projective transformation matrix for varying distances
      between the sensors and possible targets. To do so we designed a unique
      experimental setup including unique Artificial Control Points (ACPs) and their
      detection algorithms for the two sensors. We demonstrate the utility of our
      approach using different experiments and evaluation criteria. 

PMID- 26308001
TI  - Lipid Multilayer Grating Arrays Integrated by Nanointaglio for Vapor Sensing by
      an Optical Nose.
AB  - Lipid multilayer gratings are recently invented nanomechanical sensor elements
      that are capable of transducing molecular binding to fluid lipid multilayers into
      optical signals in a label free manner due to shape changes in the lipid
      nanostructures. Here, we show that nanointaglio is suitable for the integration
      of chemically different lipid multilayer gratings into a sensor array capable of
      distinguishing vapors by means of an optical nose. Sensor arrays composed of six
      different lipid formulations are integrated onto a surface and their optical
      response to three different vapors (water, ethanol and acetone) in air as well as
      pH under water is monitored as a function of time. Principal component analysis
      of the array response results in distinct clustering indicating the suitability
      of the arrays for distinguishing these analytes. Importantly, the nanointaglio
      process used here is capable of producing lipid gratings out of different
      materials with sufficiently uniform heights for the fabrication of an optical
      nose. 

PMID- 26308002
TI  - A Context-Aware EEG Headset System for Early Detection of Driver Drowsiness.
AB  - Driver drowsiness is a major cause of mortality in traffic accidents worldwide.
      Electroencephalographic (EEG) signal, which reflects the brain activities, is
      more directly related to drowsiness. Thus, many Brain-Machine-Interface (BMI)
      systems have been proposed to detect driver drowsiness. However, detecting driver
      drowsiness at its early stage poses a major practical hurdle when using existing
      BMI systems. This study proposes a context-aware BMI system aimed to detect
      driver drowsiness at its early stage by enriching the EEG data with the intensity
      of head-movements. The proposed system is carefully designed for low-power
      consumption with on-chip feature extraction and low energy Bluetooth connection.
      Also, the proposed system is implemented using JAVA programming language as a
      mobile application for on-line analysis. In total, 266 datasets obtained from six
      subjects who participated in a one-hour monotonous driving simulation experiment
      were used to evaluate this system. According to a video-based reference, the
      proposed system obtained an overall detection accuracy of 82.71% for classifying
      alert and slightly drowsy events by using EEG data alone and 96.24% by using the
      hybrid data of head-movement and EEG. These results indicate that the combination
      of EEG data and head-movement contextual information constitutes a robust
      solution for the early detection of driver drowsiness. 

PMID- 26308003
TI  - Reliable Fusion of Stereo Matching and Depth Sensor for High Quality Dense Depth
      Maps.
AB  - Depth estimation is a classical problem in computer vision, which typically
      relies on either a depth sensor or stereo matching alone. The depth sensor
      provides real-time estimates in repetitive and textureless regions where stereo
      matching is not effective. However, stereo matching can obtain more accurate
      results in rich texture regions and object boundaries where the depth sensor
      often fails. We fuse stereo matching and the depth sensor using their
      complementary characteristics to improve the depth estimation. Here, texture
      information is incorporated as a constraint to restrict the pixel's scope of
      potential disparities and to reduce noise in repetitive and textureless regions.
      Furthermore, a novel pseudo-two-layer model is used to represent the relationship
      between disparities in different pixels and segments. It is more robust to
      luminance variation by treating information obtained from a depth sensor as prior
      knowledge. Segmentation is viewed as a soft constraint to reduce ambiguities
      caused by under- or over-segmentation. Compared to the average error rate 3.27%
      of the previous state-of-the-art methods, our method provides an average error
      rate of 2.61% on the Middlebury datasets, which shows that our method performs
      almost 20% better than other "fused" algorithms in the aspect of precision. 

PMID- 26308004
TI  - A Self-Assessment Stereo Capture Model Applicable to the Internet of Things.
AB  - The realization of the Internet of Things greatly depends on the information
      communication among physical terminal devices and informationalized platforms,
      such as smart sensors, embedded systems and intelligent networks. Playing an
      important role in information acquisition, sensors for stereo capture have gained
      extensive attention in various fields. In this paper, we concentrate on promoting
      such sensors in an intelligent system with self-assessment capability to deal
      with the distortion and impairment in long-distance shooting applications. The
      core design is the establishment of the objective evaluation criteria that can
      reliably predict shooting quality with different camera configurations. Two types
      of stereo capture systems-toed-in camera configuration and parallel camera
      configuration-are taken into consideration respectively. The experimental results
      show that the proposed evaluation criteria can effectively predict the visual
      perception of stereo capture quality for long-distance shooting. 

PMID- 26308005
TI  - Effect of an Introduced Phytoene Synthase Gene Expression on Carotenoid
      Biosynthesis in the Marine Diatom Phaeodactylum tricornutum.
AB  - Carotenoids exert beneficial effects on human health through their excellent
      antioxidant activity. To increase carotenoid productivity in the marine Pennales
      Phaeodactylum tricornutum, we genetically engineered the phytoene synthase gene
      (psy) to improve expression because RNA-sequencing analysis has suggested that
      the expression level of psy is lower than other enzyme-encoding genes that are
      involved in the carotenoid biosynthetic pathway. We isolated psy from P.
      tricornutum, and this gene was fused with the enhanced green fluorescent protein
      gene to detect psy expression. After transformation using the microparticle
      bombardment technique, we obtained several P. tricornutum transformants and
      confirmed psy expression in their plastids. We investigated the amounts of PSY
      mRNA and carotenoids, such as fucoxanthin and beta-carotene, at different growth
      phases. The introduction of psy increased the fucoxanthin content of a
      transformants by approximately 1.45-fold relative to the levels in the wild-type
      diatom. However, some transformants failed to show a significant increase in the
      carotenoid content relative to that of the wild-type diatom. We also found that
      the amount of PSY mRNA at log phase might contribute to the increase in
      carotenoids in the transformants at stationary phase. 

PMID- 26308006
TI  - Proteins and Carbohydrates from Red Seaweeds: Evidence for Beneficial Effects on
      Gut Function and Microbiota.
AB  - Based on their composition, marine algae, and namely red seaweeds, are good
      potential functional foods. Intestinal mucosal barrier function refers to the
      capacity of the intestine to provide adequate containment of luminal
      microorganisms and molecules. Here, we will first outline the component of
      seaweeds and will summarize the effects of these on the regulation of mucosal
      barrier function. Special attention will be paid to unique components of red
      seaweeds: proteins and derived peptides (e.g., phycobiliproteins, glycoproteins
      that contain "cellulose binding domains", phycolectins and the related
      mycosporine-like amino acids) together with polysaccharides (e.g., floridean
      starch and sulfated galactans, such as carrageenans, agarans and "dl-hybrid") and
      minerals. These compounds have been shown to exert prebiotic effects, to regulate
      intestinal epithelial cell, macrophage and lymphocyte proliferation and
      differentiation and to modulate the immune response. Molecular mechanisms of
      action of peptides and polysaccharides are starting to be elucidated, and
      evidence indicating the involvement of epidermal growth factor receptor (EGFR),
      insulin-like growth factor receptor (IGFR), Toll-like receptors (TLR) and signal
      transduction pathways mediated by protein kinase B (PKB or AKT), nuclear factor
      kappaB (NF-kappaB) and mitogen activated protein kinases (MAPK) will also be
      summarized. The need for further research is clear, but in vivo experiments point
      to an overall antiinflammatory effect of these algae, indicating that they can
      reinforce membrane barrier function. 

PMID- 26308007
TI  - Antioxidant, Anti-Nephrolithe Activities and in Vitro Digestibility Studies of
      Three Different Cyanobacterial Pigment Extracts.
AB  - Phycobiliprotein-containing water and carotenoid-containing methanolic extracts
      of three different cyanobacteria, Pseudanabaena sp., Spirulina sp. and Lyngbya
      sp., were studied for their DPPH scavenging, iso-bolographic studies, and anti
      nephrolithe activities. The best EC50 values for DPPH scavenging were in Lyngbya
      water (LW, 18.78 +/- 1.57 mg.mg(-1) DPPH) and Lyngbya methanol (LM, 59.56 +/-
      37.38 mg.mg(-1) DPPH) extracts. Iso-bolographic analysis revealed most of the
      combinations of extracts were antagonistic to each other, although LM-Spirulina
      methanol (SM) 1:1 had the highest synergistic rate of 86.65%. In vitro digestion
      studies showed that DPPH scavenging activity was considerably decreased in all
      extracts except for Pseudanabaena methanol (PM) and LM after the simulated
      digestion. All of the extracts were effective in reducing the calcium oxalate
      crystal size by nearly 60%-65% compared to negative control, while PM and
      Spirulina water (SW) extracts could inhibit both nucleation and aggregation of
      calcium oxalate by nearly 60%-80%. 

PMID- 26308008
TI  - The Anti-Inflammatory Effect of Algae-Derived Lipid Extracts on
      Lipopolysaccharide (LPS)-Stimulated Human THP-1 Macrophages.
AB  - Algae contain a number of anti-inflammatory bioactive compounds such as omega-3
      polyunsaturated fatty acids (n-3 PUFA) and chlorophyll a, hence as dietary
      ingredients, their extracts may be effective in chronic inflammation-linked
      metabolic diseases such as cardiovascular disease. In this study, anti
      inflammatory potential of lipid extracts from three red seaweeds (Porphyra
      dioica, Palmaria palmata and Chondrus crispus) and one microalga (Pavlova
      lutheri) were assessed in lipopolysaccharide (LPS)-stimulated human THP-1
      macrophages. Extracts contained 34%-42% total fatty acids as n-3 PUFA and 5%-7%
      crude extract as pigments, including chlorophyll a, beta-carotene and
      fucoxanthin. Pretreatment of the THP-1 cells with lipid extract from P. palmata
      inhibited production of the pro-inflammatory cytokines interleukin (IL)-6 (p <
      0.05) and IL-8 (p < 0.05) while that of P. lutheri inhibited IL-6 (p < 0.01)
      production. Quantitative gene expression analysis of a panel of 92 genes linked
      to inflammatory signaling pathway revealed down-regulation of the expression of
      14 pro-inflammatory genes (TLR1, TLR2, TLR4, TLR8, TRAF5, TRAF6, TNFSF18, IL6R,
      IL23, CCR1, CCR4, CCL17, STAT3, MAP3K1) by the lipid extracts. The lipid extracts
      effectively inhibited the LPS-induced pro-inflammatory signaling pathways
      mediated via toll-like receptors, chemokines and nuclear factor kappa-light-chain
      enhancer of activated B cells (NF-kappaB) signaling molecules. These results
      suggest that lipid extracts from P. lutheri, P. palmata, P. dioica and C. crispus
      can inhibit LPS-induced inflammatory pathways in human macrophages. Therefore,
      algal lipid extracts should be further explored as anti-inflammatory ingredients
      for chronic inflammation-linked metabolic diseases. 

PMID- 26308009
TI  - Hunt for Palytoxins in a Wide Variety of Marine Organisms Harvested in 2010 on
      the French Mediterranean Coast.
AB  - During the summer of 2010, 31 species including fish, echinoderms, gastropods,
      crustaceans, cephalopods and sponges were sampled in the Bay of Villefranche on
      the French Mediterranean coast and screened for the presence of PLTX-group toxins
      using the haemolytic assay. Liquid chromatography tandem mass spectrometry (LC
      MS/MS) was used for confirmatory purposes and to determine the toxin profile. The
      mean toxin concentration in the whole flesh of all sampled marine organisms,
      determined using the lower- (LB) and upper-bound (UB) approach was 4.3 and 5.1
      ug.kg(-1), respectively, with less than 1% of the results exceeding the European
      Food Safety Authority (EFSA) threshold of 30 ug.kg(-1)and the highest values
      being reported for sea urchins (107.6 and 108.0 ug.kg(-1)). Toxins accumulated
      almost exclusively in the digestive tube of the tested species, with the
      exception of octopus, in which there were detectable toxin amounts in the
      remaining tissues (RT). The mean toxin concentration in the RT of the sampled
      organisms (fishes, echinoderms and cephalopods) was 0.7 and 1.7 ug.kg(-1) (LB and
      UB, respectively), with a maximum value of 19.9 ug.kg(-1) for octopus RT. The
      herbivorous and omnivorous organisms were the most contaminated species,
      indicating that diet influences the contamination process, and the LC-MS/MS
      revealed that ovatoxin-a was the only toxin detected. 

PMID- 26308011
TI  - High-Level Expression, Purification and Large-Scale Production of l-Methionine
      gamma-Lyase from Idiomarina as a Novel Anti-Leukemic Drug.
AB  - l-Methionine gamma-lyase (MGL), a pyridoxal 5'-phosphate-dependent enzyme,
      possesses anti-tumor activity. However, the low activity of MGL blocks the anti
      tumor effect. This study describes an efficient production process for the
      recombinant MGL (rMGL) from Idiomarina constructed using the overexpression
      plasmid in Escherichia coli BL21 (DE3), purification, and large-scale production.
      The enzyme produced by the transformants accounted for 53% of the total proteins
      and accumulated at 1.95 mg/mL using a 500 L fermentor. The enzyme was purified to
      approximately 99% purity using a high-pressure mechanical homogenizer and nickel
      (Ni) Sepharose 6 Fast Flow (FF) chromatography. Then, the enzyme was polished by
      gel filtration, the endotoxins were removed using diethyl-aminoethanol (DEAE)
      Sepharose FF, and the final product was lyophilized with a vacuum freeze dryer at
      -35  degrees C. The specific activity of rMGL in the lyophilized powder was up to
      108 U/mg. Compared to the control, the enzyme significantly inhibited cellular
      proliferation in a concentration-dependent manner as tested using the MTS (3-(4,5
      dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H
      tetrazolium) assay and induced cellular apoptosis as analyzed by Annexin V
      fluorescein isothiocyanate (FITC) with fluorescence-activated cell sorting (FACS)
      in leukemia cells. This paper demonstrated the cloning, overexpression, and large
      scale production protocols for rMGL, which enabled rMGL to be used as a novel
      anti-leukemic drug. 

PMID- 26308010
TI  - Potential Bioactive Compounds from Seaweed for Diabetes Management.
AB  - Diabetes mellitus is a group of metabolic disorders of the endocrine system
      characterised by hyperglycaemia. Type II diabetes mellitus (T2DM) constitutes the
      majority of diabetes cases around the world and are due to unhealthy diet,
      sedentary lifestyle, as well as rise of obesity in the population, which warrants
      the search for new preventive and treatment strategies. Improved comprehension of
      T2DM pathophysiology provided various new agents and approaches against T2DM
      including via nutritional and lifestyle interventions. Seaweeds are rich in
      dietary fibres, unsaturated fatty acids, and polyphenolic compounds. Many of
      these seaweed compositions have been reported to be beneficial to human health
      including in managing diabetes. In this review, we discussed the diversity of
      seaweed composition and bioactive compounds which are potentially useful in
      preventing or managing T2DM by targeting various pharmacologically relevant
      routes including inhibition of enzymes such as alpha-glucosidase, alpha-amylase,
      lipase, aldose reductase, protein tyrosine phosphatase 1B (PTP1B) and dipeptidyl
      peptidase-4 (DPP-4). Other mechanisms of action identified, such as anti
      inflammatory, induction of hepatic antioxidant enzymes' activities, stimulation
      of glucose transport and incretin hormones release, as well as beta-cell
      cytoprotection, were also discussed by taking into consideration numerous in
      vitro, in vivo, and human studies involving seaweed and seaweed-derived agents. 

PMID- 26308012
TI  - Carotenoids from Haloarchaea and Their Potential in Biotechnology.
AB  - The production of pigments by halophilic archaea has been analysed during the
      last half a century. The main reasons that sustains this research are: (i) many
      haloarchaeal species possess high carotenoids production availability; (ii)
      downstream processes related to carotenoid isolation from haloarchaea is
      relatively quick, easy and cheap; (iii) carotenoids production by haloarchaea can
      be improved by genetic modification or even by modifying several cultivation
      aspects such as nutrition, growth pH, temperature, etc.; (iv) carotenoids are
      needed to support plant and animal life and human well-being; and (v) carotenoids
      are compounds highly demanded by pharmaceutical, cosmetic and food markets.
      Several studies about carotenoid production by haloarchaea have been reported so
      far, most of them focused on pigments isolation or carotenoids production under
      different culture conditions. However, the understanding of carotenoid
      metabolism, regulation, and roles of carotenoid derivatives in this group of
      extreme microorganisms remains mostly unrevealed. The uses of those haloarchaeal
      pigments have also been poorly explored. This work summarises what has been
      described so far about carotenoids production by haloarchaea and their potential
      uses in biotechnology and biomedicine. In particular, new scientific evidence of
      improved carotenoid production by one of the better known haloarchaeon (Haloferax
      mediterranei) is also discussed. 

PMID- 26308013
TI  - Astaxanthin Improves Human Sperm Capacitation by Inducing Lyn Displacement and
      Activation.
AB  - Astaxanthin (Asta), a photo-protective red pigment of the carotenoid family, is
      known for its multiple beneficial properties. In this study, the effects of Asta
      on isolated human sperm were evaluated. Capacitation involves a series of
      transformations to let sperm acquire the correct features for potential oocyte
      fertilization, including the generation of a controlled amount of reactive oxygen
      species (ROS), cholesterol depletion of the sperm outer membrane, and protein
      tyrosine phosphorylation (Tyr-P) process in the head region. Volunteers, with
      normal spermiogram values, were divided in two separate groups on the basis of
      their ability to generate the correct content of endogenous ROS. Both patient
      group (PG) and control group (CG) were analysed for Tyr-phosphorylation (Tyr-P)
      pattern and percentages of acrosome-reacted cells (ARC) and non-viable cells
      (NVC), in the presence or absence of Asta. In addition, the involvement of ROS on
      membrane reorganization and the presence of Lyn, a Src family kinase associated
      with lipid rafts, were investigated. Results show that Lyn is present in the
      membranes of human sperm, mainly confined in midpiece in resting conditions.
      Following capacitation, Lyn translocated to the head concomitantly with raft
      relocation, thus allowing the Tyr-P of head proteins. Asta succeeded to trigger
      Lyn translocation in PG sperm thus bypassing the impaired ROS-related mechanism
      for rafts and Lyn translocation. In this study, we showed an interdependence
      between ROS generation and lipid rafts and Lyn relocation leading the cells to
      undergo the successive acrosome reaction (AR). Asta, by ameliorating PG sperm
      functioning, may be utilised to decrease male idiopathic infertility. 

PMID- 26308014
TI  - Sphingosines Derived from Marine Sponge as Potential Multi-Target Drug Related to
      Disorders in Cancer Development.
AB  - Haliclona tubifera, marine sponge species abundant in Brazilian coastline,
      presents only a few papers published in the literature. Recently, we have
      reported the isolation of two modified C18 sphingoid bases: (2R,3R,6R,7Z)-2
      aminooctadec-7-ene-1,3, 6-triol and and (2R,3R,6R)-2-aminooctadec-1,3,6-triol. In
      order to continue our research, in this work aimed at the biological
      investigation of fractions that led to the isolation of these compounds. We
      evaluated the cytotoxic effect of marine sponge H. tubifera fractions in glioma
      (U87) and neuroblastoma (SH-SY5Y) human cell lines. In addition, considering the
      link between cancer, imbalance of reactive oxygen species and coagulation
      disorders, we also investigated the in vitro effects on blood coagulation and
      their redox properties. We showed that the ethyl acetate (EtOAc) fraction, rich
      in sphingoid bases, had important cytotoxic effects in both cancer cell lines
      with an IC50 < 15 MUg/mL and also can inhibit the production of peroxyl radicals.
      Interestingly, this fraction increased the recalcification time of human blood,
      showing anticoagulant properties. The present study indicates the sphingosines
      fraction as a promising source of chemical prototypes, especially multifunctional
      drugs in cancer therapy. 

PMID- 26308015
TI  - A Web-Based Respondent Driven Sampling Pilot Targeting Young People at Risk for
      Chlamydia Trachomatis in Social and Sexual Networks with Testing: A Use
      Evaluation.
AB  - BACKGROUND: With the aim of targeting high-risk hidden heterosexual young people
      for Chlamydia trachomatis (CT) testing, an innovative web-based screening
      strategy using Respondent Driven Sampling (RDS) and home-based CT testing, was
      developed, piloted and evaluated. METHODS: Two STI clinic nurses encouraged 37 CT
      positive heterosexual young people (aged 16-25 years), called index clients, to
      recruit peers from their social and sexual networks using the web-based screening
      strategy. Eligible peers (young, living in the study area) could request a home
      based CT test and recruit other peers. RESULTS: Twelve (40%) index clients
      recruited 35 peers. Two of these peers recruited other peers (n = 7). In total,
      35 recruited peers were eligible for participation; ten of them (29%) requested a
      test and eight tested. Seven tested for the first time and one (13%) was
      positive. Most peers were female friends (80%). Nurses were positive about using
      the strategy. CONCLUSIONS: The screening strategy is feasible for targeting the
      hidden social network. However, uptake among men and recruitment of sex-partners
      is low and RDS stopped early. Future studies are needed to explore the
      sustainability, cost-effectiveness, and impact of strategies that target people
      at risk who are not effectively reached by regular health care.

PMID- 26308016
TI  - Theoretical Framework for Plastic Waste Management in Ghana through Extended
      Producer Responsibility: Case of Sachet Water Waste.
AB  - Currently, use and disposal of plastic by consumers through waste management
      activities in Ghana not only creates environmental problems, but also reinforces
      the notion of a wasteful society. The magnitude of this problem has led to
      increasing pressure from the public for efficient and practical measures to solve
      the waste problem. This paper analyses the impact of plastic use and disposal in
      Ghana. It emphasizes the need for commitment to proper management of the impacts
      of plastic waste and effective environmental management in the country.
      Sustainable Solid Waste Management (SSWM) is a critical problem for developing
      countries with regards to climate change and greenhouse gas emission, and also
      the general wellbeing of the populace. Key themes of this paper are producer
      responsibility and management of products at end of life. The paper proposes two
      theatrical recovery models that can be used to address the issue of sachet waste
      in Ghana. 

PMID- 26308017
TI  - Combining HJ CCD, GF-1 WFV and MODIS Data to Generate Daily High Spatial
      Resolution Synthetic Data for Environmental Process Monitoring.
AB  - The limitations of satellite data acquisition mean that there is a lack of
      satellite data with high spatial and temporal resolutions for environmental
      process monitoring. In this study, we address this problem by applying the
      Enhanced Spatial and Temporal Adaptive Reflectance Fusion Model (ESTARFM) and the
      Spatial and Temporal Data Fusion Approach (STDFA) to combine Huanjing satellite
      charge coupled device (HJ CCD), Gaofen satellite no. 1 wide field of view camera
      (GF-1 WFV) and Moderate Resolution Imaging Spectroradiometer (MODIS) data to
      generate daily high spatial resolution synthetic data for land surface process
      monitoring. Actual HJ CCD and GF-1 WFV data were used to evaluate the precision
      of the synthetic images using the correlation analysis method. Our method was
      tested and validated for two study areas in Xinjiang Province, China. The results
      show that both the ESTARFM and STDFA can be applied to combine HJ CCD and MODIS
      reflectance data, and GF-1 WFV and MODIS reflectance data, to generate synthetic
      HJ CCD data and synthetic GF-1 WFV data that closely match actual data with
      correlation coefficients (r) greater than 0.8989 and 0.8643, respectively.
      Synthetic red- and near infrared (NIR)-band data generated by ESTARFM are more
      suitable for the calculation of Normalized Different Vegetation Index (NDVI) than
      the data generated by STDFA. 

PMID- 26308018
TI  - An IBCLC in the Maternity Ward of a Mother and Child Hospital: A Pre- and Post
      Intervention Study.
AB  - Published evidence on the impact of the integration of International Board
      Certified Lactation Consultants (IBCLCs) for breastfeeding promotion is growing,
      but still relatively limited. Our study aims at evaluating the effects of adding
      an IBCLC for breastfeeding support in a mother and child hospital environment. We
      conducted a prospective study in the maternity ward of our maternal and child
      health Institute, recruiting 402 mothers of healthy term newborns soon after
      birth. The 18-month intervention of the IBCLC (Phase II) was preceded (Phase I)
      by data collection on breastfeeding rates and factors related to breastfeeding,
      both at hospital discharge and two weeks later. Data collection was replicated
      just before the end of the intervention (Phase III). In Phase III, a
      significantly higher percentage of mothers: (a) received help to breastfeed, and
      also received correct information on breastfeeding and community support, (b)
      started breastfeeding within two hours from delivery, (c) reported a good
      experience with the hospital staff. Moreover, the frequency of sore and/or
      cracked nipples was significantly lower in Phase III. However, no difference was
      found in exclusive breastfeeding rates at hospital discharge or at two weeks
      after birth. 

PMID- 26308019
TI  - The Association between Noise, Cortisol and Heart Rate in a Small-Scale Gold
      Mining Community-A Pilot Study.
AB  - We performed a cross-sectional pilot study on salivary cortisol, heart rate, and
      personal noise exposures in a small-scale gold mining village in northeastern
      Ghana in 2013. Cortisol level changes between morning and evening among
      participants showed a relatively low decline in cortisol through the day (-1.44
      +/- 4.27 nmol/L, n = 18), a pattern consistent with chronic stress. A multiple
      linear regression, adjusting for age, sex, smoking status, and time between
      samples indicated a significant increase of 0.25 nmol/L cortisol from afternoon
      to evening per 1 dBA increase in equivalent continuous noise exposure (Leq) over
      that period (95% CI: 0.08-0.42, Adj R(2) = 0.502, n = 17). A mixed effect linear
      regression model adjusting for age and sex indicated a significant increase of
      0.29 heart beats per minute (BPM) for every 1 dB increase in Leq. Using standard
      deviations (SDs) as measures of variation, and adjusting for age and sex over the
      sampling period, we found that a 1 dBA increase in noise variation over time (Leq
      SD) was associated with a 0.5 BPM increase in heart rate SD (95% CI: 0.04--0.9,
      Adj. R(2) = 0.229, n = 16). Noise levels were consistently high, with 24-hour
      average Leq exposures ranging from 56.9 to 92.0 dBA, with a mean daily Leq of
      82.2 +/- 7.3 dBA (mean monitoring duration 22.1 +/- 1.9 hours, n = 22). Ninety
      five percent of participants had 24-hour average Leq noise levels over the 70 dBA
      World health Organization (WHO) guideline level for prevention of hearing loss.
      These findings suggest that small-scale mining communities may face multiple,
      potentially additive health risks that are not yet well documented, including
      hearing loss and cardiovascular effects of stress and noise. 

PMID- 26308020
TI  - Monetary Valuation of PM10-Related Health Risks in Beijing China: The Necessity
      for PM10 Pollution Indemnity.
AB  - Severe health risks caused by PM10 (particulate matter with an aerodynamic
      diameter <=10 MUm) pollution have induced inevitable economic losses and have
      rendered pressure on the sustainable development of society as a whole. In China,
      with the "Polluters Pay Principle", polluters should pay for the pollution they
      have caused, but how much they should pay remains an intractable problem for
      policy makers. This paper integrated an epidemiological exposure-response model
      with economics methods, including the Amended Human Capital (AHC) approach and
      the Cost of Illness (COI) method, to value the economic loss of PM10-related
      health risks in 16 districts and also 4 functional zones in Beijing from 2008 to
      2012. The results show that from 2008 to 2012 the estimated annual deaths caused
      by PM10 in Beijing are around 56,000, 58,000, 63,000, 61,000 and 59,000,
      respectively, while the economic losses related to health damage increased from
      around 23 to 31 billion dollars that PM10 polluters should pay for pollution
      victims between 2008 and 2012. It is illustrated that not only PM10 concentration
      but also many other social economic factors influence PM10-related health
      economic losses, which makes health economic losses show a time lag discrepancy
      compared with the decline of PM10 concentration. In conclusion, health economic
      loss evaluation is imperative in the pollution indemnity system establishment and
      should be considered for the urban planning and policy making to control the
      burgeoning PM10 health economic loss. 

PMID- 26308021
TI  - E-Cigarettes: A Review of New Trends in Cannabis Use.
AB  - The emergence of electronic cigarettes (e-cigs) has given cannabis smokers a new
      method of inhaling cannabinoids. E-cigs differ from traditional marijuana
      cigarettes in several respects. First, it is assumed that vaporizing cannabinoids
      at lower temperatures is safer because it produces smaller amounts of toxic
      substances than the hot combustion of a marijuana cigarette. Recreational
      cannabis users can discretely "vape" deodorized cannabis extracts with minimal
      annoyance to the people around them and less chance of detection. There are
      nevertheless several drawbacks worth mentioning: although manufacturing
      commercial (or homemade) cannabinoid-enriched electronic liquids (e-liquids)
      requires lengthy, complex processing, some are readily on the Internet despite
      their lack of quality control, expiry date, and conditions of preservation and,
      above all, any toxicological and clinical assessment. Besides these safety
      problems, the regulatory situation surrounding e-liquids is often unclear. More
      simply ground cannabis flowering heads or concentrated, oily THC extracts (such
      as butane honey oil or BHO) can be vaped in specially designed, pen-sized
      marijuana vaporizers. Analysis of a commercial e-liquid rich in cannabidiol
      showed that it contained a smaller dose of active ingredient than advertised;
      testing our laboratory-made, purified BHO, however, confirmed that it could be
      vaped in an e-cig to deliver a psychoactive dose of THC. The health consequences
      specific to vaping these cannabis preparations remain largely unknown and
      speculative due to the absence of comprehensive, robust scientific studies. The
      most significant health concerns involve the vaping of cannabinoids by children
      and teenagers. E-cigs could provide an alternative gateway to cannabis use for
      young people. Furthermore, vaping cannabinoids could lead to environmental and
      passive contamination. 

PMID- 26308022
TI  - Use of the Monocyte-to-Lymphocyte Ratio to Predict Diabetic Retinopathy.
AB  - BACKGROUND: Diabetic retinopathy (DR) is a common complication of type 2 diabetes
      mellitus (T2DM) and the leading cause of blindness in adults. DR pathogenesis has
      not been fully elucidated, but inflammation is widely accepted to play an
      important role. Emerging evidence suggests that the platelet-to-lymphocyte ratio
      (PLR), monocyte-to-lymphocyte ratio (MLR), and neutrophil-to-lymphocyte ratio
      (NLR) are novel potential markers of inflammatory responses. The present study
      aimed to evaluate the associations between DR and the PLR, MLR, and NLR. PATIENTS
      AND METHODS: We performed a case-control study involving 247 patients with T2DM.
      The patients were divided into three groups: 125 control subjects with T2DM, 63
      diabetic subjects with non-proliferative diabetic retinopathy (NPDR), and 59
      patients with proliferative diabetic retinopathy (PDR). RESULTS: The mean PLR and
      NLR were significantly higher in patients with DR compared with patients without
      DR (p < 0.01, p = 0.02, respectively). The mean MLR in the NPDR group was higher
      than that of patients without DR, but there were no significant differences among
      the three groups (p = 0.07). Logistic regression showed that the MLR was an
      independent risk factor for DR (odds ratio [OR]: 54.574, 95% confidence interval
      [CI]: 2.708-1099.907). Based on the receiver operating characteristic (ROC)
      curve, use of the MLR as an indicator for DR diagnosis was projected to be 2.25,
      and yielded a sensitivity and specificity of 47.1% and 69.6%, respectively, with
      an area under the curve of 0.581 (95% CI: 0.510-0.653). CONCLUSIONS: The PLR and
      NLR are significantly increased in the setting of DR. After correcting for
      possible confounding factors, the MLR was found to be a risk factor for DR.
      Although the MLR may be pathophysiologically and clinically relevant in DR, its
      predictive ability was limited.

PMID- 26308023
TI  - An Investigation of Organic and Inorganic Mercury Exposure and Blood Pressure in
      a Small-Scale Gold Mining Community in Ghana.
AB  - There is increasing concern about the cardiovascular effects of mercury (Hg)
      exposure, and that organic methylmercury and inorganic Hg(2+) may affect the
      cardiovascular system and blood pressure differentially. In small-scale gold
      mining communities where inorganic, elemental Hg exposures are high, little is
      known about the effects of Hg on blood pressure. In 2011, we assessed the
      relationship between Hg exposure and blood pressure (BP) in a cross-sectional
      study of adults from a small-scale gold mining community, Kejetia, and
      subsistence farming community, Gorogo, in Ghana's Upper East Region.
      Participants' resting heart rate and BP were measured, and hair and urine samples
      were provided to serve as biomarkers of organic and inorganic Hg exposure,
      respectively. Participants included 70 miners and 26 non-miners from Kejetia and
      75 non-miners from Gorogo. Total specific gravity-adjusted urinary and hair Hg
      was higher among Kejetia miners than Kejetia non-miners and Gorogo participants
      (median urinary Hg: 5.17, 1.18, and 0.154 ug/L, respectively; hair Hg: 0.945,
      0.419, and 0.181 ug/g, respectively). Hypertension was prevalent in 17.7% of
      Kejetia and 21.3% of Gorogo participants. Urinary and hair Hg were not
      significantly associated with systolic or diastolic BP for Kejetia or Gorogo
      participants while adjusting for sex, age, and smoking status. Although our
      results follow trends seen in other studies, the associations were not of
      statistical significance. Given the unique study population and high exposures to
      inorganic Hg, the work contained here will help increase our understanding of the
      cardiovascular effects of Hg. 

PMID- 26308024
TI  - A Better Antiviral Efficacy Found in Nucleos(t)ide Analog (NA) Combinations with
      Interferon Therapy than NA Monotherapy for HBeAg Positive Chronic Hepatitis B: A
      Meta-Analysis.
AB  - BACKGROUND: The clinical efficacy of nucleos(t)ide analogues (NAs) combined with
      interferon (IFN) therapy vs. NAs monotherapy for chronic hepatitis B (CHB)
      remains inconclusive. The aim of this meta-analysis was to determine whether the
      NAs plus IFN regimen offers synergistic efficacy that justifies the cost and
      burden of such a combination therapy in CHB patients. METHODS: Related
      publications covering the period of 1966 to July 2014 were identified through
      searching MEDLINE, EMBASE, Cochrane library, Chinese Biomedical Literature
      Database, WANFANG, and CNKI database. A total of 17 studies were enrolled,
      including 6 in English and 11 in Chinese. Then, we established a final list of
      studies for the meta-analysis by systematically grading the quality and
      eligibility of the identified individual studies. We used hepatitis B antigen
      (HBeAg) loss, HBV-DNA undetectable rate, HBeAg seroconversion, hepatitis B
      surface antigen (HBsAg) loss, HBsAg seroconversion, and histological score at the
      end of treatment for efficacy evaluation. A quantitative meta-analysis (Review
      Manager, Version 5.1.0) was performed to assess the differences between NAs and
      IFN combination therapy and NAs monotherapy. RESULTS: Our analysis demonstrated
      that HBeAg loss (RR = 1.73, 95% CI = 1.32-2.26, p < 0.001), HBV-DNA undetectable
      rate (RR = 1.58, 95% CI = 1.22-2.04, p < 0.001), HBeAg seroconversion (RR = 1.68,
      95% CI = 1.36-2.07, p < 0.001), and HBsAg loss (RR = 2.51, 95% CI = 1.32-4.75, p
      < 0.001) in the combination therapy group were significantly higher than those in
      the monotherapy group. However, there were no significant differences in HBsAg
      seroconversion (RR = 4.25, 95% CI = 0.62-29.13, p = 0.14), sustained virological
      response rates, and biochemical response rates observed between the two groups.
      The results showed that the combination therapy group had more improved HBV
      histology than the NAs monotherapy group (RR = 1.14, 95% CI = 0.93-1.39, p =
      0.22). CONCLUSIONS: NAs and IFN or Peg-IFN combination therapy had a better
      efficacy in terms of HBeAg loss, HBV-DNA undetectable rate, HBeAg seroconversion,
      and HBsAg loss, compared to the NA monotherapy group at the end of treatment;
      however, there was no significant difference in HBsAg seroconversion between the
      two regimens.

PMID- 26308025
TI  - Accelerating Aerobic Sludge Granulation by Adding Dry Sewage Sludge Micropowder
      in Sequencing Batch Reactors.
AB  - Micropowder (20-250 um) made from ground dry waste sludge from a municipal sewage
      treatment plant was added in a sequencing batch reactor (R2), which was fed by
      synthetic wastewater with acetate as carbon source. Compared with the traditional
      SBR (R1), aerobic sludge granulation time was shortened 15 days in R2.
      Furthermore, filamentous bacteria in bulking sludge were controlled to accelerate
      aerobic granulation and form large granules. Correspondingly, the SVI decreased
      from 225 mL/g to 37 mL/g. X-ray Fluorescence (XRF) analysis demonstrated that Al
      and Si from the micropowder were accumulated in granules. A mechanism hypotheses
      for the acceleration of aerobic granulation by adding dry sludge micropowder is
      proposed: added micropowder acts as nuclei to induce bacterial attachment;
      dissolved matters from the micropowder increase abruptly the organic load for
      starved sludge to control overgrown filamentous bacteria as a framework for
      aggregation; increased friction from the movement of micropowder forces the
      filaments which extend outwards to shrink for shaping granules. 

PMID- 26308026
TI  - Older People's Perceptions of Pedestrian Friendliness and Traffic Safety: An
      Experiment Using Computer-Simulated Walking Environments.
AB  - Traffic safety and pedestrian friendliness are considered to be important
      conditions for older people's motivation to walk through their environment. This
      study uses an experimental study design with computer-simulated living
      environments to investigate the effect of micro-scale environmental factors
      (parking spaces and green verges with trees) on older people's perceptions of
      both motivational antecedents (dependent variables). Seventy-four consecutively
      recruited older people were randomly assigned watching one of two scenarios
      (independent variable) on a computer screen. The scenarios simulated a stroll on
      a sidewalk, as it is 'typical' for a German city. In version 'A,' the subjects
      take a fictive walk on a sidewalk where a number of cars are parked partially on
      it. In version 'B', cars are in parking spaces separated from the sidewalk by
      grass verges and trees. Subjects assessed their impressions of both dependent
      variables. A multivariate analysis of covariance showed that subjects' ratings on
      perceived traffic safety and pedestrian friendliness were higher for Version 'B'
      compared to version 'A'. Cohen's d indicates medium (d = 0.73) and large (d =
      1.23) effect sizes for traffic safety and pedestrian friendliness, respectively.
      The study suggests that elements of the built environment might affect
      motivational antecedents of older people's walking behavior. 

PMID- 26308027
TI  - Prevalence of Genes of OXA-23 Carbapenemase and AdeABC Efflux Pump Associated
      with Multidrug Resistance of Acinetobacter baumannii Isolates in the ICU of a
      Comprehensive Hospital of Northwestern China.
AB  - The objective of this study was to explore the molecular epidemiology and the
      genetic support of clinical multidrug resistant (MDR) Acinetobacter baumannii (A.
      baumannii) isolates in an ICU ward of a comprehensive hospital. A total of 102
      non-duplicate drug-resistant A. baumannii isolates were identified and 93 (91.1%)
      of them were MDR strains. Molecular analysis demonstrated that carbapenemase
      genes blaOXA-23 and blaOXA-51 were presented in all 93 MDR isolates (100%), but
      other carbapenemase genes, including blaOXA-24, blaOXA-58, blaIMP-1, blaIMP-4,
      blaSIM, and blaVIM genes were completely absent in all isolates. In addition,
      genes of AdeABC efflux system were detected in 88.2% (90/102) isolates.
      Interestingly, an addition to efflux pump inhibitor, reserpine could
      significantly enhance the susceptibility of MDR isolates to moxifloxacin,
      cefotaxime, and imipenem (p < 0.01). Clonal relationship analysis further grouped
      these clinical drug-resistant isolates into nine clusters, and the MDR strains
      were mainly in clusters A, B, C, and D, which include 16, 13, 25, and 15
      isolates, respectively. This study demonstrated that clinical isolates carrying
      carbapenemase-encoding genes blaOXA-23 and AdeABC efflux pump genes are the main
      prevalent MDR A. baumannii, and the co-expression of oxacillinase and efflux pump
      proteins are thus considered to be the important reason for the prevalence of
      this organism in the ICU of this hospital. 

PMID- 26308028
TI  - Prevalence and Characterization of Integrons in Multidrug Resistant Acinetobacter
      baumannii in Eastern China: A Multiple-Hospital Study.
AB  - OBJECTIVE: The aim of this multiple-hospital study was to investigate the
      prevalence of integrons in multidrug-resistant Acinetobacter baumannii (MDRAB) in
      Eastern China, and characterize the integron-integrase genes, so as to provide
      evidence for the management and appropriate antibiotic use of MDRAB infections.
      METHODS: A total of 425 clinical isolates of A. baumannii were collected from 16
      tertiary hospitals in 11 cities of four provinces (Fujian, Jiangsu, Zhejiang and
      Shandong) from January 2009 to June 2012. The susceptibility of A. baumannii
      isolates to ampicillin/sulbactam, piperacillin/tazobactam, ceftazidime,
      ceftriaxone, cefepime, aztreonam, meropenem, amikacin, gentamicin, tobramycin,
      ciprofloxacin, levofloxacin, sulfamethoxazole/trimenthoprim, minocycline and
      imipenem was tested, and integrons and their gene cassettes were characterized in
      these isolates using PCR assay. In addition, integron-positive A. baumannii
      isolates were genotyped using pulsed-field gel electrophoresis (PFGE) assay, and
      intI1 gene cassette was sequenced. RESULTS: intI1 gene was carried in 69.6% of
      total A. baumannii isolates, while intI2 and intI3 genes were not detected. The
      prevalence of resistance to ampicillin/sulbactam, piperacillin/tazobactam,
      ceftazidime, ceftriaxone, cefepime, aztreonam, imipenem, meropenem, amikacin,
      gentamicin, tobramycin, ciprofloxacin, levofloxacin and
      sulfamethoxazole/trimenthoprim was significantly higher in integron-positive A.
      baumannii isolates than in negative isolates (all p values <0.05), while no
      significant difference was observed in the prevalence of minocycline resistance
      (p > 0.05). PFGE assay revealed 27 PFGE genotypes and 4 predominant genotypes,
      P1, P4, P7 and P19. The PFGE genotype P1 contained 13 extensive-drug resistant
      and 89 non-extensive-drug resistant A. baumannii isolates, while the genotype P4
      contained 34 extensive-drug resistant and 67 non-extensive-drug resistant
      isolates, appearing a significant antimicrobial resistance pattern (both p values
      <0.05). Sequencing analysis revealed two gene cassette assays of aacA4-catB8
      aadA1 and dfrXII-orfF-aadA2 in MDRAB isolates. CONCLUSIONS: The results of this
      study demonstrate a high prevalence of class 1 integrons in MDRAB in Eastern
      China, and a greater prevalence of antimicrobial resistance in intI1 gene
      positive MDRAB isolates than in negative isolates. Four predominant PFGE
      genotypes are identified in intI1 gene-positive MDRAB isolates, in which P4 is an
      epidemic PFGE genotype in Fujian Province, and it has a high proportion of
      extensive drug resistant A. baumannii. The gene cassette dfrXII-orfF-aadA2 is
      reported, for the first time, in A. baumannii strains isolated from Fujian
      Province, Eastern China.

PMID- 26308029
TI  - Mindfulness, Physical Activity and Avoidance of Secondhand Smoke: A Study of
      College Students in Shanghai.
AB  - INTRODUCTION: To better understand the documented link between mindfulness and
      longevity, we examine the association between mindfulness and conscious avoidance
      of secondhand smoke (SHS), as well as the association between mindfulness and
      physical activity. METHOD: In Shanghai University of Finance and Economics (SUFE)
      we surveyed a convenience sample of 1516 college freshmen. We measured
      mindfulness, weekly physical activity, and conscious avoidance of secondhand
      smoke, along with demographic and behavioral covariates. We used a multilevel
      logistic regression to test the association between mindfulness and conscious
      avoidance of secondhand smoke, and used a Tobit regression model to test the
      association between mindfulness and metabolic equivalent hours per week. In both
      models the home province of the student respondent was used as the cluster
      variable, and demographic and behavioral covariates, such as age, gender, smoking
      history, household registration status (urban vs. rural), the perceived smog
      frequency in their home towns, and the asthma diagnosis. RESULTS: The logistic
      regression of consciously avoiding SHS shows that a higher level of mindfulness
      was associated with an increase in the odds ratio of conscious SHS avoidance
      (logged odds: 0.22, standard error: 0.07, p < 0.01). The Tobit regression shows
      that a higher level of mindfulness was associated with more metabolic equivalent
      hours per week (Tobit coefficient: 4.09, standard error: 1.13, p < 0.001).
      DISCUSSION: This study is an innovative attempt to study the behavioral issue of
      secondhand smoke from the perspective of the potential victim, rather than the
      active smoker. The observed associational patterns here are consistent with
      previous findings that mindfulness is associated with healthier behaviors in
      obesity prevention and substance use. Research designs with interventions are
      needed to test the causal link between mindfulness and these healthy behaviors.

PMID- 26308030
TI  - Microbiological Food Safety for Vulnerable People.
AB  - Foodborne pathogens are more likely to cause infection and to result in serious
      consequences in vulnerable people than in healthy adults. People with some
      increase in susceptibility may form nearly 20% of the population in the UK and
      the USA. Conditions leading to increased susceptibility are listed. The main
      factors leading to foodborne disease caused by major pathogens are outlined and
      examples are given of outbreaks resulting from these factors. Measures to prevent
      foodborne disease include procedures based on Hazard Analysis Critical Control
      Point principles and prerequisite programmes and, especially for vulnerable
      people, the use of lower-risk foods in place of higher-risk products. 

PMID- 26308031
TI  - A Population-Based, Nationwide Cross-Sectional Study on Influenza Vaccination
      Status among Cancer Survivors in Korea.
AB  - Cancer survivors are at increased risk of developing influenza-related
      complications. The purpose of this study was to investigate the vaccination
      coverage among cancer survivors in Korea using the Korea National Health and
      Nutrition Examination Survey (KNHANES). Adult cancer survivors were selected from
      fourth (2007-2009) and fifth (2010-2012) KNHANES (n = 1156) datasets. General
      characteristics, cancer-related data, and influenza vaccination status were
      collected using self-report questionnaires. Chi-square tests and multiple
      logistic regression analyses were performed to investigate the association
      between influenza vaccination coverage and associated factors. Overall, 51% of
      survivors were vaccinated. Vaccine prevalence exceeded 75% in those more than 65
      years but was only 26% in survivors aged 19-44. Increasing age, low frequency of
      alcohol consumption, having poor self-rated health, and having a shorter duration
      since cancer diagnosis were significant predictors of vaccination status among
      cancer survivors under 65 years of age. Influenza vaccine coverage remains much
      lower than recommended among cancer survivors, particularly in the younger age
      groups. Further study is needed to determine the factors that contribute to the
      lack of vaccination in cancer survivors, despite their increased risk for
      influenza. 

PMID- 26308032
TI  - Identification of Major Risk Sources for Surface Water Pollution by Risk Indexes
      (RI) in the Multi-Provincial Boundary Region of the Taihu Basin, China.
AB  - Environmental safety in multi-district boundary regions has been one of the
      focuses in China and is mentioned many times in the Environmental Protection Act
      of 2014. Five types were categorized concerning the risk sources for surface
      water pollution in the multi-provincial boundary region of the Taihu basin:
      production enterprises, waste disposal sites, chemical storage sites,
      agricultural non-point sources and waterway transportations. Considering the
      hazard of risk sources, the purification property of environmental medium and the
      vulnerability of risk receptors, 52 specific attributes on the risk levels of
      each type of risk source were screened out. Continuous piecewise linear function
      model, expert consultation method and fuzzy integral model were used to calculate
      the integrated risk indexes (RI) to characterize the risk levels of pollution
      sources. In the studied area, 2716 pollution sources were characterized by RI
      values. There were 56 high-risk sources screened out as major risk sources,
      accounting for about 2% of the total. The numbers of sources with high-moderate,
      moderate, moderate-low and low pollution risk were 376, 1059, 101 and 1124,
      respectively, accounting for 14%, 38%, 5% and 41% of the total. The procedure
      proposed could be included in the integrated risk management systems of the multi
      district boundary region of the Taihu basin. It could help decision makers to
      identify major risk sources in the risk prevention and reduction of surface water
      pollution. 

PMID- 26308033
TI  - Characterization of the Bacterial Community Naturally Present on Commercially
      Grown Basil Leaves: Evaluation of Sample Preparation Prior to Culture-Independent
      Techniques.
AB  - Fresh herbs such as basil constitute an important food commodity worldwide. Basil
      provides considerable culinary and health benefits, but has also been implicated
      in foodborne illnesses. The naturally occurring bacterial community on basil
      leaves is currently unknown, so the epiphytic bacterial community was
      investigated using the culture-independent techniques denaturing gradient gel
      electrophoresis (DGGE) and next-generation sequencing (NGS). Sample preparation
      had a major influence on the results from DGGE and NGS: Novosphingobium was the
      dominant genus for three different basil batches obtained by maceration of basil
      leaves, while washing of the leaves yielded lower numbers but more variable
      dominant bacterial genera including Klebsiella, Pantoea, Flavobacterium,
      Sphingobacterium and Pseudomonas. During storage of basil, bacterial growth and
      shifts in the bacterial community were observed with DGGE and NGS. Spoilage was
      not associated with specific bacterial groups and presumably caused by
      physiological tissue deterioration and visual defects, rather than by bacterial
      growth. 

PMID- 26308034
TI  - Effect of Smoking Reduction Therapy on Smoking Cessation for Smokers without an
      Intention to Quit: An Updated Systematic Review and Meta-Analysis of Randomized
      Controlled.
AB  - OBJECTIVE: Effective strategies are needed to encourage smoking cessation for
      smokers without an intention to quit. We systematically reviewed the literature
      to investigate whether smoking reduction therapy can increase the long-term
      cessation rates of smokers without an intention to quit. METHODS: PubMed, Embase,
      and CENTRAL (Cochrane Central Register of Controlled Trials) were searched for
      randomized controlled trials (RCTs) on the effect of smoking reduction therapy on
      long-term smoking cessation in smokers without an intention to quit. The primary
      outcome was the cessation rate at the longest follow-up period. A random effects
      model was used to calculate pooled relative risks (RRs) and 95% confidence
      intervals (CIs). RESULTS: Fourteen trials with a total of 7981 smokers were
      included. The pooled analysis suggested that reduction support plus medication
      significantly increased the long-term cessation of smokers without an intention
      to quit compared to reduction support plus placebo (RR, 1.97; 95% CI, 1.44-2.7;
      I(2), 52%) or no intervention (RR, 1.93; 95% CI, 1.41-2.64; I(2), 46%). In a
      subgroup of smokers who received varenicline or nicotine replacement therapy
      (NRT), the differences were also statistically significant. This suggests the
      safety of using NRT. The percentage of smokers with serious adverse events who
      discontinued because of these events in the non-NRT group was slightly
      significantly different than in the control group. Insufficient evidence is
      available to test the efficacy of reduction behavioural support in promoting long
      term cessation among this population. CONCLUSIONS: The present meta-analysis
      indicated the efficacy of NRT- and varenicline-assisted reduction to achieve
      complete cessation among smokers without an intention to quit. Further evidence
      is needed to assess the efficacy and safety of reduction behavioural support and
      bupropion.

PMID- 26308036
TI  - Investigation of E. coli and Virus Reductions Using Replicate, Bench-Scale
      Biosand Filter Columns and Two Filter Media.
AB  - The biosand filter (BSF) is an intermittently operated, household-scale slow sand
      filter for which little data are available on the effect of sand composition on
      treatment performance. Therefore, bench-scale columns were prepared according to
      the then-current (2006-2007) guidance on BSF design and run in parallel to
      conduct two microbial challenge experiments of eight-week duration. Triplicate
      columns were loaded with Accusand silica or crushed granite to compare virus and
      E. coli reduction performance. Bench-scale experiments provided confirmation that
      increased schmutzdecke growth, as indicated by decline in filtration rate, is the
      primary factor causing increased E. coli reductions of up to 5-log10. However,
      reductions of challenge viruses improved only modestly with increased
      schmutzdecke growth. Filter media type (Accusand silica vs. crushed granite) did
      not influence reduction of E. coli bacteria. The granite media without
      backwashing yielded superior virus reductions when compared to Accusand. However,
      for columns in which the granite media was first backwashed (to yield a more
      consistent distribution of grains and remove the finest size fraction), virus
      reductions were not significantly greater than in columns with Accusand media. It
      was postulated that a decline in surface area with backwashing decreased the
      sites and surface area available for virus sorption and/or biofilm growth and
      thus decreased the extent of virus reduction. Additionally, backwashing caused
      preferential flow paths and deviation from plug flow; backwashing is not part of
      standard BSF field preparation and is not recommended for BSF column studies.
      Overall, virus reductions were modest and did not meet the 5- or 3-log10 World
      Health Organization performance targets. 

PMID- 26308035
TI  - Detection of Antibiotic Resistant Staphylococcus aureus from Milk: A Public
      Health Implication.
AB  - The aim of this study was to investigate the occurrence, antibiotic
      susceptibility profiles, and virulence genes determinants of S. aureus isolated
      from milk obtained from retail outlets of the North-West Province, South Africa.
      To achieve this, 200 samples of raw, bulk and pasteurised milk were obtained
      randomly from supermarkets, shops and some farms in the North-West Province
      between May 2012 and April 2013. S. aureus was isolated and positively identified
      using morphological (Gram staining), biochemical (DNase, catalase, haemolysis and
      rapid slide agglutination) tests, protein profile analysis (MALDI-TOF mass
      spectrometry) and molecular (nuc specific PCR) methods. The antimicrobial
      resistance profiles of the isolates were determined using the phenotypic agar
      diffusion method. Genes encoding enterotoxins, exfoliative toxins and collagen
      adhesins were also screened using PCR. Among all the samples examined, 30 of 40
      raw milk samples (75%), 25 of 85 bulk milk samples (29%) and 10 of 75 pasteurised
      milk samples (13%) were positive for S. aureus. One hundred and fifty-six PCR
      confirmed S. aureus isolates were obtained from 75 contaminated milk samples. A
      large proportion (60%-100%) of the isolates was resistant to penicillin G,
      ampicillin, oxacillin, vancomycin, teicoplanin and erythromycin. On the contrary,
      low level resistance (8.3%-40%) was observed for gentamicin, kanamycin and
      sulphamethoxazole. Methicillin resistance was detected in 59% of the multidrug
      resistant isolates and this was a cause for concern. However, only a small
      proportion (20.6%) of these isolates possessed PBP2a which codes for Methicillin
      resistance in S. aureus. In addition, 32.7% of isolates possessed the sec gene
      whereas the sea, seb sed, see, cna, eta, etb genes were not detected. The
      findings of this study showed that raw, bulk and pasteurised milk in the North
      West Province is contaminated with toxigenic and multi-drug resistant S. aureus
      strains. There is a need to implement appropriate control measures to reduce
      contamination as well as the spread of virulent S. aureus strains and the burden
      of disease in humans. 

PMID- 26308037
TI  - Metabolic Degradation of 1,4-dichloronaphthalene by Pseudomonas sp. HY.
AB  - There is increasing concern regarding the adverse health effects of
      polychlorinated naphthalenes (PCNs). The metabolic degradation of 1,4
      dichloronaphthalene (1,4-DCN) as a model PCN, was studied using a strain of
      Pseudomonas sp. HY. The metabolites were analyzed by gas chromatography-mass
      spectrometry (GC-MS). A series of metabolites including dihydroxy-dichloro
      naphthalene, epoxy-dichlorinated naphthalene, dichlorinated naphthol, and
      dichlorinated salicylic acid were identified. The time-concentration plots of the
      degradation curves of 1,4-DCN was also obtained from the experiments, which set
      the initial concentration of 1,4-DCN to 10 mg/L and 20 mg/L, respectively. The
      results showed that 98% removal could be achieved within 48 h at an initial 1,4
      DCN concentration of 10 mg/L. Nevertheless, it took 144 h to reach the same
      degradation efficiency at an initial concentration of 20 mg/L. The degradation of
      1,4-DCN may not remove the chloride ions during the processes and the metabolites
      may not benefit the bacterial growth. The research suggests a metabolic pathway
      of 1,4-DCN, which is critical for the treatment of this compound through
      biological processes. 

PMID- 26308038
TI  - Field Application of the Micro Biological Survey Method for a Simple and
      Effective Assessment of the Microbiological Quality of Water Sources in
      Developing Countries.
AB  - According to the World Health Organization (WHO) guidelines, "safe drinking-water
      must not represent any significant risk to health over a lifetime of consumption,
      including different sensitivities that may occur between life stages".
      Traditional methods of water analysis are usually complex, time consuming and
      require an appropriately equipped laboratory, specialized personnel and expensive
      instrumentation. The aim of this work was to apply an alternative method, the
      Micro Biological Survey (MBS), to analyse for contaminants in drinking water.
      Preliminary experiments were carried out to demonstrate the linearity and
      accuracy of the MBS method and to verify the possibility of using the evaluation
      of total coliforms in 1 mL of water as a sufficient parameter to roughly though
      accurately determine water microbiological quality. The MBS method was then
      tested "on field" to assess the microbiological quality of water sources in the
      city of Douala (Cameroon, Central Africa). Analyses were performed on both dug
      and drilled wells in different periods of the year. Results confirm that the MBS
      method appears to be a valid and accurate method to evaluate the microbiological
      quality of many water sources and it can be of valuable aid in developing
      countries. 

PMID- 26308039
TI  - Measuring Disability: Comparing the Impact of Two Data Collection Approaches on
      Disability Rates.
AB  - The usual approach in disability surveys is to screen persons with disability
      upfront and then ask questions about everyday problems. The objectives of this
      paper are to demonstrate the impact of screeners on disability rates, to
      challenge the usual exclusion of persons with mild and moderate disability from
      disability surveys and to demonstrate the advantage of using an a posteriori cut
      off. Using data of a pilot study of the WHO Model Disability Survey (MDS) in
      Cambodia and the polytomous Rasch model, metric scales of disability were built.
      The conventional screener approach based on the short disability module of the
      Washington City Group and the a posteriori cut-off method described in the World
      Disability Report were compared regarding disability rates. The screener led to
      imprecise rates and classified persons with mild to moderate disability as non
      disabled, although these respondents already experienced important problems in
      daily life. The a posteriori cut-off applied to the general population sample led
      to a more precise disability rate and allowed for a differentiation of the
      performance and needs of persons with mild, moderate and severe disability. This
      approach can be therefore considered as an inclusive approach suitable to monitor
      the Convention on the Rights of Persons with Disabilities. 

PMID- 26308040
TI  - Thyroid Autoimmunity is Associated with Decreased Cytotoxicity T Cells in Women
      with Repeated Implantation Failure.
AB  - Thyroid autoimmunity (TAI), which is defined as the presence of autoantibodies
      against thyroid peroxidase (TPO) and/or thyroglobulin (TG), is related to
      repeated implantation failure (RIF). It is reported that TAI was involved in
      reproductive failure not only through leading thyroid function abnormality, but
      it can also be accompanied with immune imbalance. Therefore, this study was
      designed to investigate the association of thyroid function, immune status and
      TAI in women with RIF. Blood samples were drawn from 72 women with RIF to
      evaluate the prevalence of TAI, the thyroid function, the absolute numbers and
      percentages of lymphocytes. The prevalence of thyroid function abnormality in RIF
      women with TAI was not significantly different from that in RIF women without TAI
      (c(2) = 0.484, p > 0.05). The absolute number and percentage of T cells, T helper
      (Th) cells, B cells and natural killer (NK) cells were not significantly
      different in RIF women with TAI compared to those without TAI (all p > 0.05). The
      percentage of T cytotoxicity (Tc) cells was significantly decreased in RIF women
      with TAI compared to those without TAI (p < 0.05). Meanwhile, Th/Tc ratio was
      significantly increased (p < 0.05). These results indicated that the decreased Tc
      percentage and increased Th/Tc ratio may be another influential factor of adverse
      pregnancy outcomes in RIF women with TAI. 

PMID- 26308041
TI  - Artificial TALE as a Convenient Protein Platform for Engineering Broad-Spectrum
      Resistance to Begomoviruses.
AB  - Transcription activator-like effectors (TALEs) are a class of sequence-specific
      DNA-binding proteins that utilize a simple and predictable modality to recognize
      target DNA. This unique characteristic allows for the rapid assembly of
      artificial TALEs, with high DNA binding specificity, to any target DNA sequences
      for the creation of customizable sequence-specific nucleases used in genome
      engineering. Here, we report the use of an artificial TALE protein as a
      convenient platform for designing broad-spectrum resistance to begomoviruses, one
      of the most destructive plant virus groups, which cause tremendous losses
      worldwide. We showed that artificial TALEs, which were assembled based on
      conserved sequence motifs within begomovirus genomes, could confer partial
      resistance in transgenic Nicotiana benthamiana to all three begomoviruses tested.
      Furthermore, the resistance was maintained even in the presence of their
      betasatellite. These results shed new light on the development of broad-spectrum
      resistance against DNA viruses, such as begomoviruses. 

PMID- 26308042
TI  - Oral Application of T4 Phage Induces Weak Antibody Production in the Gut and in
      the Blood.
AB  - A specific humoral response to bacteriophages may follow phage application for
      medical purposes, and it may further determine the success or failure of the
      approach itself. We present a long-term study of antibody induction in mice by T4
      phage applied per os: 100 days of phage treatment followed by 112 days without
      the phage, and subsequent second application of phage up to day 240. Serum and
      gut antibodies (IgM, IgG, secretory IgA) were analyzed in relation to
      microbiological status of the animals. T4 phage applied orally induced anti-phage
      antibodies when the exposure was long enough (IgG day 36, IgA day 79); the effect
      was related to high dosage. Termination of phage treatment resulted in a decrease
      of IgA again to insignificant levels. Second administration of phage induces
      secretory IgA sooner than that induced by the first administrations. Increased
      IgA level antagonized gut transit of active phage. Phage resistant E. coli
      dominated gut flora very late, on day 92. Thus, the immunological response
      emerges as a major factor determining phage survival in the gut. Phage proteins
      Hoc and gp12 were identified as highly immunogenic. A low response to exemplary
      foreign antigens (from Ebola virus) presented on Hoc was observed, which suggests
      that phage platforms can be used in oral vaccine design. 

PMID- 26308043
TI  - Cloak and Dagger: Alternative Immune Evasion and Modulation Strategies of
      Poxviruses.
AB  - As all viruses rely on cellular factors throughout their replication cycle, to be
      successful they must evolve strategies to evade and/or manipulate the defence
      mechanisms employed by the host cell. In addition to their expression of a wide
      array of host modulatory factors, several recent studies have suggested that
      poxviruses may have evolved unique mechanisms to shunt or evade host detection.
      These potential mechanisms include mimicry of apoptotic bodies by mature virions
      (MVs), the use of viral sub-structures termed lateral bodies for the packaging
      and delivery of host modulators, and the formation of a second, "cloaked" form of
      infectious extracellular virus (EVs). Here we discuss these various strategies
      and how they may facilitate poxvirus immune evasion. Finally we propose a model
      for the exploitation of the cellular exosome pathway for the formation of EVs. 

PMID- 26308045
TI  - Screening for Methylated Poly(l-histidine) with Various
      Dimethylimidazolium/Methylimidazole/Imidazole Contents as DNA Carrier.
AB  - : Methylated poly(l-histidine) (PLH-Me), our original polypeptide, has controlled
      the contents of dimethylimidazolium, tau/pi-methylimidazole and imidazole groups
      for efficient gene delivery. The screening for the PLH-Me as DNA carrier has been
      carried out by use of the PLH with 25 mol% (tau-methyl, 16 mol%; pi-methyl, 17
      mol%; deprotonated imidazole, 41 mol%), 68 mol% (tau-methyl, 16 mol%; pi-methyl,
      8 mol%; deprotonated imidazole, 8 mol%) and 87 mol% (tau-methyl, 7 mol%; pi
      methyl, 4 mol%; deprotonated imidazole, 2 mol%) dimethylimidazolium groups, that
      is, PLH-Me(25), PLH-Me(68) and PLH-Me(87), respectively. The screening of the
      chemical structure of PLH-Me has been carried out for DNA carrier properties,
      which are the stability of its DNA polyion complexes and gene expression. The DNA
      complexes with the 25 mol% and 68 mol% dimethylated PLH-Me possessed almost same
      ability to retain DNA, as compared with the 87 mol% dimethylated PLH-Me, which
      was examined by competitive exchange with dextran sulfate. From the gene
      transfection experiment against HepG2 cells, human hepatoma cell line, the PLH
      Me(25)/DNA complex was revealed to mediate highest gene expression. These results
      suggest that the dimethyl-imidazolium/methylimidazole/imidazole balance of the
      PLH-Me is important for DNA carrier design. 

PMID- 26308044
TI  - Image-Guided Hydrodynamic Gene Delivery: Current Status and Future Directions.
AB  - Hydrodynamics-based delivery has been used as an experimental tool to express
      transgene in small animals. This in vivo gene transfer method is useful for
      functional analysis of genetic elements, therapeutic effect of oligonucleotides,
      and cancer cells to establish the metastatic cancer animal model for experimental
      research. Recent progress in the development of image-guided procedure for
      hydrodynamics-based gene delivery in large animals directly supports the clinical
      applicability of this technique. This review summarizes the current status and
      recent progress in the development of hydrodynamics-based gene delivery and
      discusses the future directions for its clinical application. 

PMID- 26308046
TI  - Aqueous Extract of Nypa fruticans Wurmb. Vinegar Alleviates Postprandial
      Hyperglycemia in Normoglycemic Rats.
AB  - Nypa fruticans Wurmb. vinegar, commonly known as nipa palm vinegar (NPV) has been
      used as a folklore medicine among the Malay community to treat diabetes. Early
      work has shown that aqueous extract (AE) of NPV exerts a potent antihyperglycemic
      effect. Thus, this study is conducted to evaluate the effect of AE on
      postprandial hyperglycemia in an attempt to understand its mechanism of
      antidiabetic action. AE were tested via in vitro intestinal glucose absorption,
      in vivo carbohydrate tolerance tests and spectrophotometric enzyme inhibition
      assays. One mg/mL of AE showed a comparable outcome to the use of phloridzin (1
      mM) in vitro as it delayed glucose absorption through isolated rat jejunum more
      effectively than acarbose (1 mg/mL). Further in vivo confirmatory tests showed AE
      (500 mg/kg) to cause a significant suppression in postprandial hyperglycemia 30
      min following respective glucose (2 g/kg), sucrose (4 g/kg) and starch (3 g/kg)
      loadings in normal rats, compared to the control group. Conversely, in
      spectrophotometric enzymatic assays, AE showed rather a weak inhibitory activity
      against both alpha-glucosidase and alpha-amylase when compared with acarbose. The
      findings suggested that NPV exerts its anti-diabetic effect by delaying
      carbohydrate absorption from the small intestine through selective inhibition of
      intestinal glucose transporters, therefore suppressing postprandial
      hyperglycemia. 

PMID- 26308047
TI  - A Comparison of the Sodium Content of Supermarket Private-Label and Branded Foods
      in Australia.
AB  - Supermarket private-label products are perceived to be lower quality than their
      branded counterparts. Excess dietary sodium in foods contributes to high blood
      pressure and cardiovascular disease. Sodium concentrations in products are an
      important indicator of quality. We compared the sodium content of 15,680
      supermarket private-label and branded products, available in four Australian
      supermarkets between 2011-2013, overall and for 15 food categories. Mean sodium
      values were compared for: (1) all products in 2013; (2) products in both 2011 and
      2013; and (3) products only in 2013. Comparisons were made using paired and
      unpaired t tests. In each year the proportion of supermarket private-label
      products was 31%-32%, with overall mean sodium content 17% (12%-23%) lower than
      branded products in 2013 (p <= 0.001). For products available in both 2011 and
      2013 there was a <=2% (1%-3%) mean sodium reduction overall with no difference in
      reformulation between supermarket private-label and branded products (p = 0.73).
      New supermarket private-label products in 2013 were 11% lower in sodium than
      their branded counterparts (p = 0.02). Supermarket private-label products
      performed generally better than branded in terms of their sodium content. Lower
      sodium intake translates into lower blood pressure; some supermarket private
      label products may be a good option for Australians needing to limit their sodium
      intake. 

PMID- 26308048
TI  - Feasibility of Recruiting Families into a Heart Disease Prevention Program Based
      on Dietary Patterns.
AB  - Offspring of parents with a history of cardiovascular disease (CVD) inherit a
      similar genetic profile and share diet and lifestyle behaviors. This study aimed
      to evaluate the feasibility of recruiting families at risk of CVD to a dietary
      prevention program, determine the changes in diet achieved, and program
      acceptability. Families were recruited into a pilot parallel group randomized
      controlled trial consisting of a three month evidence-based dietary intervention,
      based on the Mediterranean and Portfolio diets. Feasibility was assessed by
      recruitment and retention rates, change in diet by food frequency questionnaire,
      and program acceptability by qualitative interviews and program evaluation.
      Twenty one families were enrolled over 16 months, with fourteen families (n = 42
      individuals) completing the study. Post-program dietary changes in the
      intervention group included small daily increases in vegetable serves (0.8 +/-
      1.3) and reduced usage of full-fat milk (-21%), cheese (-12%) and meat products (
      17%). Qualitative interviews highlighted beneficial changes in food purchasing
      habits. Future studies need more effective methods of recruitment to engage
      families in the intervention. Once engaged, families made small incremental
      improvements in their diets. Evaluation indicated that feedback on diet and CVD
      risk factors, dietetic counselling and the resources provided were appropriate
      for a program of this type. 

PMID- 26308049
TI  - Sources and Amounts of Animal, Dairy, and Plant Protein Intake of US Adults in
      2007-2010.
AB  - Dietary guidelines suggest consuming a mixed-protein diet, consisting of high
      quality animal, dairy, and plant-based foods. However, current data on the
      distribution and the food sources of protein intake in a free-living,
      representative sample of US adults are not available. Data from the National
      Health and Nutrition Examination Survey (NHANES), 2007-2010, were used in these
      analyses (n = 10,977, age >= 19 years). Several US Department of Agriculture
      (USDA) databases were used to partition the composition of foods consumed into
      animal, dairy, or plant components. Mean +/- SE animal, dairy, and plant protein
      intakes were determined and deciles of usual intakes were estimated. The
      percentages of total protein intake derived from animal, dairy, and plant protein
      were 46%, 16%, and 30%, respectively; 8% of intake could not be classified.
      Chicken and beef were the primary food sources of animal protein intake. Cheese,
      reduced-fat milk, and ice cream/dairy desserts were primary sources of dairy
      protein intake. Yeast breads, rolls/buns, and nuts/seeds were primary sources of
      plant protein intake. This study provides baseline data for assessing the
      effectiveness of public health interventions designed to alter the composition of
      protein foods consumed by the American public. 

PMID- 26308051
TI  - Zearalenone and Its Derivatives alpha-Zearalenol and beta-Zearalenol
      Decontamination by Saccharomyces cerevisiae Strains Isolated from Bovine Forage.
AB  - Zearalenone (ZEA) and its derivatives are mycotoxins with estrogenic effects on
      mammals. The biotransformation for ZEA in animals involves the formation of two
      major metabolites, alpha- and beta-zearalenol (alpha-ZOL and beta-ZOL), which are
      subsequently conjugated with glucuronic acid. The capability of Saccharomyces
      cerevisiae strains isolated from silage to eliminate ZEA and its derivatives
      alpha-ZOL and beta-ZOL was investigated as, also, the mechanisms involved.
      Strains were grown on Yeast Extract-Peptone-Dextrose medium supplemented with the
      mycotoxins and their elimination from medium was quantified over time by HPLC-FL.
      A significant effect on the concentration of ZEA was observed, as all the tested
      strains were able to eliminate more than 90% of the mycotoxin from the culture
      medium in two days. The observed elimination was mainly due to ZEA
      biotransformation into beta-ZOL (53%) and alpha-ZOL (8%) rather than to its
      adsorption to yeast cells walls. Further, the biotransformation of alpha-ZOL was
      not observed but a small amount of beta-ZOL (6%) disappeared from culture medium.
      ZEA biotransformation by yeasts may not be regarded as a full detoxification
      process because both main end-products are still estrogenic. Nonetheless, it was
      observed that the biotransformation favors the formation of beta-ZOL which is
      less estrogenic than ZEA and alpha-ZOL. This metabolic effect is only possible if
      active strains are used as feed additives and may play a role in the
      detoxification performance of products with viable S. cerevisiae cells. 

PMID- 26308050
TI  - Genetic Factors Involved in Fumonisin Accumulation in Maize Kernels and Their
      Implications in Maize Agronomic Management and Breeding.
AB  - Contamination of maize with fumonisins depends on the environmental conditions;
      the maize resistance to contamination and the interaction between both factors.
      Although the effect of environmental factors is a determinant for establishing
      the risk of kernel contamination in a region, there is sufficient genetic
      variability among maize to develop resistance to fumonisin contamination and to
      breed varieties with contamination at safe levels. In addition, ascertaining
      which environmental factors are the most important in a region will allow the
      implementation of risk monitoring programs and suitable cultural practices to
      reduce the impact of such environmental variables. The current paper reviews all
      works done to address the influence of environmental variables on fumonisin
      accumulation, the genetics of maize resistance to fumonisin accumulation, and the
      search for the biochemical and/or structural mechanisms of the maize plant that
      could be involved in resistance to fumonisin contamination. We also explore the
      outcomes of breeding programs and risk monitoring of undertaken projects. 

PMID- 26308052
TI  - Presence of Multiple Mycotoxins and Other Fungal Metabolites in Native Grasses
      from a Wetland Ecosystem in Argentina Intended for Grazing Cattle.
AB  - The aim of this study was to evaluate the occurrence of several fungal
      metabolites, including mycotoxins in natural grasses (Poaceae) intended for
      grazing cattle. A total number of 72 and 77 different metabolites were detected
      on 106 and 69 grass samples collected during 2011 and 2014, respectively. A total
      of 60 metabolites were found across both years. Among the few mycotoxins
      considered toxic for ruminants, no samples of natural grasses were contaminated
      with aflatoxins, ochratoxin A, ergot alkaloids, and gliotoxin, among others.
      However, we were able to detect important metabolites (toxic to ruminants) such
      as type A trichothecenes, mainly T-2 toxin and HT-2 toxin (up to 5000 ug/kg
      each), and zearalenone (up to 2000 ug/kg), all at very high frequencies and
      levels. Other fungal metabolites that were found to be prevalent were other
      Fusarium metabolites like beauvericin, equisetin and aurofusarin, metabolites
      produced by Alternaria spp., sterigmatocystin and its precursors and
      anthrachinone derivatives. It is important to point out that the profile of
      common metabolites was shared during both years of sampling, and also that the
      occurrence of important metabolites is not a sporadic event. Considering that
      this area of temperate grassland is used for grazing cattle all year long due to
      the richness in palatable grasses (Poaceae), the present work represents a
      starting point for further studies on the occurrence of multi-mycotoxins in
      natural grasses in order to have a complete picture of the extent of cattle
      exposure. Also, the present study shows that the presence of zeranol in urine of
      beef cattle may not be a consequence of illegal use of this banned substance, but
      the product of the natural occurrence of zearalenone and alpha-zearalenol in
      natural grasses intended for cattle feeding. 

PMID- 26308053
TI  - Protective Effects of Bacillus subtilis ANSB060 on Serum Biochemistry,
      Histopathological Changes and Antioxidant Enzyme Activities of Broilers Fed Moldy
      Peanut Meal Naturally Contaminated with Aflatoxins.
AB  - The aim of this study was to investigate the toxic effects of aflatoxins and
      evaluate the effectiveness of Bacillus subtilis ANSB060 in detoxifying
      aflatoxicosis in broilers. A total of 360 one-week-old male broilers (Ross 308)
      were assigned to six dietary treatments for five weeks. The treatment diets were:
      C0 (basal diet); C1.0 (C0 + 1.0 g B. subtilis ANSB060/kg diet); M0 (basal diet
      formulated with moldy peanut meal); M0.5, M1.0 and M2.0 (M0 + 0.5, 1.0 and 2.0 g
      B. subtilis ANSB060/kg diet, respectively). The contents of aflatoxin B1, B2, G1
      and G2 in the diets formulated with moldy peanut meal were 70.7 +/- 1.3, 11.0 +/-
      1.5, 6.5 +/- 0.8 and 2.0 +/- 0.3 ug/kg, respectively. The results showed that
      aflatoxins increased (p < 0.05) serum aspartate transaminase activity, decreased
      (p < 0.05) serum glutathione peroxidase activity, and enhanced (p < 0.05)
      malondialdehyde contents in both the serum and liver. Aflatoxins also caused
      gross and histological changes in liver tissues, such as bile duct epithelium
      hyperplasia, vacuolar degeneration and lymphocyte infiltration. The
      supplementation of ANSB060 reduced aflatoxin levels in the duodenum and
      counteracted the negative effects of aflatoxins, leading to the conclusion that
      ANSB060 has a protective effect against aflatoxicosis and this protection is dose
      related. 

PMID- 26308054
TI  - Signaling beyond Punching Holes: Modulation of Cellular Responses by Vibrio
      cholerae Cytolysin.
AB  - Pore-forming toxins (PFTs) are a distinct class of membrane-damaging cytolytic
      proteins that contribute significantly towards the virulence processes employed
      by various pathogenic bacteria. Vibrio cholerae cytolysin (VCC) is a prominent
      member of the beta-barrel PFT (beta-PFT) family. It is secreted by most of the
      pathogenic strains of the intestinal pathogen V. cholerae. Owing to its potent
      membrane-damaging cell-killing activity, VCC is believed to play critical roles
      in V. cholerae pathogenesis, particularly in those strains that lack the cholera
      toxin. Large numbers of studies have explored the mechanistic basis of the cell
      killing activity of VCC. Consistent with the beta-PFT mode of action, VCC has
      been shown to act on the target cells by forming transmembrane oligomeric beta
      barrel pores, thereby leading to permeabilization of the target cell membranes.
      Apart from the pore-formation-induced direct cell-killing action, VCC exhibits
      the potential to initiate a plethora of signal transduction pathways that may
      lead to apoptosis, or may act to enhance the cell survival/activation responses,
      depending on the type of target cells. In this review, we will present a concise
      view of our current understanding regarding the multiple aspects of these
      cellular responses, and their underlying signaling mechanisms, evoked by VCC. 

PMID- 26308055
TI  - Effects of Melittin Treatment in Cholangitis and Biliary Fibrosis in a Model of
      Xenobiotic-Induced Cholestasis in Mice.
AB  - Cholangiopathy is a chronic immune-mediated disease of the liver, which is
      characterized by cholangitis, ductular reaction and biliary-type hepatic
      fibrosis. There is no proven medical therapy that changes the course of the
      disease. In previous studies, melittin was known for attenuation of hepatic
      injury, inflammation and hepatic fibrosis. This study investigated whether
      melittin provides inhibition on cholangitis and biliary fibrosis in vivo. Feeding
      3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) to mice is a well-established
      animal model to study cholangitis and biliary fibrosis. To investigate the
      effects of melittin on cholangiopathy, mice were fed with a 0.1% DDC-containing
      diet with or without melittin treatment for four weeks. Liver morphology, serum
      markers of liver injury, cholestasis markers for inflammation of liver, the
      degree of ductular reaction and the degree of liver fibrosis were compared
      between with or without melittin treatment DDC-fed mice. DDC feeding led to
      increased serum markers of hepatic injury, ductular reaction, induction of pro
      inflammatory cytokines and biliary fibrosis. Interestingly, melittin treatment
      attenuated hepatic function markers, ductular reaction, the reactive phenotype of
      cholangiocytes and cholangitis and biliary fibrosis. Our data suggest that
      melittin treatment can be protective against chronic cholestatic disease in DDC
      fed mice. Further studies on the anti-inflammatory capacity of melittin are
      warranted for targeted therapy in cholangiopathy. 

PMID- 26308056
TI  - The Role of Botulinum Toxin Type A in the Clinical Management of Refractory
      Anterior Knee Pain.
AB  - Anterior knee pain is a highly prevalent condition affecting largely young to
      middle aged adults. Symptoms can recur in more than two thirds of cases, often
      resulting in activity limitation and reduced participation in employment and
      recreational pursuits. Persistent anterior knee pain is difficult to treat and
      many individuals eventually consider a surgical intervention. Evidence for long
      term benefit of most conservative treatments or surgical approaches is currently
      lacking. Injection of Botulinum toxin type A to the distal region of vastus
      lateralis muscle causes a short term functional "denervation" which moderates the
      influence of vastus lateralis muscle on the knee extensor mechanism and increases
      the relative contribution of the vastus medialis muscle. Initial data suggest
      that, compared with other interventions for anterior knee pain, Botulinum toxin
      type A injection, in combination with an active exercise programme, can lead to
      sustained relief of symptoms, reduced health care utilisation and increased
      activity participation. The procedure is less invasive than surgical
      intervention, relatively easy to perform, and is time- and cost-effective.
      Further studies, including larger randomized placebo-controlled trials, are
      required to confirm the effectiveness of Botulinum toxin type A injection for
      anterior knee pain and to elaborate the possible mechanisms underpinning pain and
      symptom relief. 

PMID- 26308057
TI  - Spatiotemporal Regulation of Nuclear Transport Machinery and Microtubule
      Organization.
AB  - Spindle microtubules capture and segregate chromosomes and, therefore, their
      assembly is an essential event in mitosis. To carry out their mission, many key
      players for microtubule formation need to be strictly orchestrated. Particularly,
      proteins that assemble the spindle need to be translocated at appropriate sites
      during mitosis. A small GTPase (hydrolase enzyme of guanosine triphosphate), Ran,
      controls this translocation. Ran plays many roles in many cellular events:
      nucleocytoplasmic shuttling through the nuclear envelope, assembly of the mitotic
      spindle, and reorganization of the nuclear envelope at the mitotic exit. Although
      these events are seemingly distinct, recent studies demonstrate that the
      mechanisms underlying these phenomena are substantially the same as explained by
      molecular interplay of the master regulator Ran, the transport factor importin,
      and its cargo proteins. Our review focuses on how the transport machinery
      regulates mitotic progression of cells. We summarize translocation mechanisms
      governed by Ran and its regulatory proteins, and particularly focus on Ran-GTP
      targets in fission yeast that promote spindle formation. We also discuss the
      coordination of the spatial and temporal regulation of proteins from the
      viewpoint of transport machinery. We propose that the transport machinery is an
      essential key that couples the spatial and temporal events in cells. 

PMID- 26308058
TI  - Mitochondrial Impairment May Increase Cellular NAD(P)H: Resazurin Oxidoreductase
      Activity, Perturbing the NAD(P)H-Based Viability Assays.
AB  - Cellular NAD(P)H-dependent oxidoreductase activity with artificial dyes (NAD(P)H
      OR) is an indicator of viability, as the cellular redox state is important for
      biosynthesis and antioxidant defense. However, high NAD(P)H due to impaired
      mitochondrial oxidation, known as reductive stress, should increase NAD(P)H-OR
      yet perturb viability. To better understand this complex behavior, we assayed
      NAD(P)H-OR with resazurin (Alamar Blue) in glioblastoma cell lines U87 and T98G,
      treated with inhibitors of central metabolism, oxythiamin, and phosphonate
      analogs of 2-oxo acids. Targeting the thiamin diphosphate (ThDP)-dependent
      enzymes, the inhibitors are known to decrease the NAD(P)H production in the
      pentose phosphate shuttle and/or upon mitochondrial oxidation of 2-oxo acids.
      Nevertheless, the inhibitors elevated NAD(P)H-OR with resazurin in a time- and
      concentration-dependent manner, suggesting impaired NAD(P)H oxidation rather than
      increased viability. In particular, inhibition of the ThDP-dependent enzymes
      affects metabolism of malate, which mediates mitochondrial oxidation of cytosolic
      NAD(P)H. We showed that oxythiamin not only inhibited mitochondrial 2-oxo acid
      dehydrogenases, but also induced cell-specific changes in glutamate and malate
      dehydrogenases and/or malic enzyme. As a result, inhibition of the 2-oxo acid
      dehydrogenases compromises mitochondrial metabolism, with the dysregulated
      electron fluxes leading to increases in cellular NAD(P)H-OR. Perturbed
      mitochondrial oxidation of NAD(P)H may thus complicate the NAD(P)H-based
      viability assay. 

PMID- 26308060
TI  - The Effects of Temperature and Growth Phase on the Lipidomes of Sulfolobus
      islandicus and Sulfolobus tokodaii.
AB  - The functionality of the plasma membrane is essential for all organisms. Adaption
      to high growth temperatures imposes challenges and Bacteria, Eukarya, and Archaea
      have developed several mechanisms to cope with these. Hyperthermophilic archaea
      have earlier been shown to synthesize tetraether membrane lipids with an
      increased number of cyclopentane moieties at higher growth temperatures. Here we
      used shotgun lipidomics to study this effect as well as the influence of growth
      phase on the lipidomes of Sulfolobus islandicus and Sulfolobus tokodaii for the
      first time. Both species were cultivated at three different temperatures, with
      samples withdrawn during lag, exponential, and stationary phases. Three abundant
      tetraether lipid classes and one diether lipid class were monitored. Beside the
      expected increase in the number of cyclopentane moieties with higher temperature
      in both archaea, we observed previously unreported changes in the average
      cyclization of the membrane lipids throughout growth. The average number of
      cyclopentane moieties showed a significant dip in exponential phase, an
      observation that might help to resolve the currently debated biosynthesis pathway
      of tetraether lipids. 

PMID- 26308059
TI  - Fitness Landscapes of Functional RNAs.
AB  - The notion of fitness landscapes, a map between genotype and fitness, was
      proposed more than 80 years ago. For most of this time data was only available
      for a few alleles, and thus we had only a restricted view of the whole fitness
      landscape. Recently, advances in genetics and molecular biology allow a more
      detailed view of them. Here we review experimental and theoretical studies of
      fitness landscapes of functional RNAs, especially aptamers and ribozymes. We find
      that RNA structures can be divided into critical structures, connecting
      structures, neutral structures and forbidden structures. Such characterisation,
      coupled with theoretical sequence-to-structure predictions, allows us to
      construct the whole fitness landscape. Fitness landscapes then can be used to
      study evolution, and in our case the development of the RNA world. 

PMID- 26308061
TI  - Prospective Lymphedema Surveillance in a Clinic Setting.
AB  - The potential impact of breast cancer-related lymphedema (LE) is quite extensive,
      yet it often remains under-diagnosed until the later stages. This project
      examines the effectiveness of prospective surveillance in post-surgical breast
      cancer patients. A retrospective analysis of 49 out of 100 patients enrolled in a
      longitudinal prospective study at a Midwestern breast center evaluates: (1) time
      required for completion of bilateral limb measurements and Lymphedema Breast
      Cancer Questionnaire (LBCQ); (2) referral to LE management with limb volume
      increase (LVI) and/or LBCQ symptoms; and (3) cost of LE management at lower LVI
      (>=5%-<=10%) versus traditional (>=10%). Findings revealed a visit timeframe mean
      of 40.3 min (range = 25-60); 43.6% of visits were <=30-min timeframe. Visit and
      measurement times decreased as clinic staff gained measurement experience;
      measurement time mean was 17.9 min (range = 16.9-18.9). LBCQ symptoms and LVI
      were significantly (p < 0.001) correlated to LE referral; six of the nine
      patients referred (67%) displayed both LBCQ symptoms/LVI. Visits with no symptoms
      reported did not result in referral, demonstrating the importance of using both
      indicators when assessing early LE. Lower threshold referral provides compelling
      evidence of potential cost savings over traditional threshold referral with
      reported costs of: $3755.00 and $6353.00, respectively (40.9% savings). 

PMID- 26308062
TI  - Systems Level Dissection of Candida Recognition by Dectins: A Matter of Fungal
      Morphology and Site of Infection.
AB  - Candida albicans is an ubiquitous fungal commensal of human skin and mucosal
      surfaces, and at the same time a major life-threatening human fungal pathogen in
      immunocompromised individuals. Host defense mechanisms rely on the capacity of
      professional phagocytes to recognize Candida cell wall antigens. During the past
      decade, the host immune response to Candida was dissected in depth, highlighting
      the essential role of C-type lectin receptors, especially regarding the power of
      the Dectins' family in discriminating between the tolerated yeast-like form of
      Candida and its invading counterpart, the hyphae. This review focuses on the
      immuno-modulatory properties of the Candida morphologies and their specific
      interactions with the host innate immune system in different body surfaces. 

PMID- 26308065
TI  - Injectable Amorphous Chitin-Agarose Composite Hydrogels for Biomedical
      Applications.
AB  - Injectable hydrogels are gaining popularity as tissue engineering constructs
      because of their ease of handling and minimal invasive delivery. Making hydrogels
      from natural polymers helps to overcome biocompatibility issues. Here, we have
      developed an Amorphous Chitin (ACh)-Agarose (Agr) composite hydrogel using a
      simpletechnique. Rheological studies, such as viscoelastic behavior (elastic
      modulus, viscous modulus, yield stress, and consistency), inversion test, and
      injectability test, were carried out for different ACh-Agr concentrations. The
      composite gel, having a concentration of 1.5% ACh and 0.25% Agr, showed good
      elastic modulus (17.3 kPa), yield stress (3.8 kPa), no flow under gravity,
      injectability, and temperature stability within the physiological range. Based on
      these studies, the optimum concentration for injectability was found to be 1.5%
      ACh and 0.25% Agr. This optimized concentration was used for further studies and
      characterized using FT-IR and SEM. FT-IR studies confirmed the presence of ACh
      and Agr in the composite gel. SEM results showed that the lyophilized composite
      gel had good porosity and mesh like networks. The cytocompatibility of the
      composite gel was studied using human mesenchymal stem cells (hMSCs). The
      composite gels showed good cell viability.These results indicated that this
      injectable composite gel can be used for biomedical applications. 

PMID- 26308064
TI  - Clinical Potential of microRNA-7 in Cancer.
AB  - microRNAs (miRNAs) are a family of short, non-coding RNA molecules that drive a
      complex network of post-transcriptional gene regulation by enhancing target mRNA
      decay and/or inhibiting protein synthesis from mRNA transcripts. They regulate
      genes involved in key aspects of normal cell growth, development and the
      maintenance of body homeostasis and have been closely linked to the development
      and progression of human disease, in particular cancer. Over recent years there
      has been much interest regarding their potential as biomarkers and as therapeutic
      agents or targets. microRNA-7 (miR-7) is a 23 nucleotide (nt) miRNA known
      primarily to act as a tumour suppressor. miR-7 directly inhibits a number of
      oncogenic targets and impedes various aspects of cancer progression in vitro and
      in vivo, however, some studies have also implicated miR-7 in oncogenic roles.
      This review summarises the role of miR-7 in cancer, its potential in miRNA-based
      replacement therapy and its capacity as both a diagnostic and prognostic
      biomarker. 

PMID- 26308063
TI  - MicroRNA Processing and Human Cancer.
AB  - MicroRNAs (miRNAs) are short non-coding RNAs of 20 to 25 nucleotides that
      regulate gene expression post-transcriptionally mainly by binding to a specific
      sequence of the 3' end of the untranslated region (3'UTR) of target genes. Since
      the first report on the clinical relevance of miRNAs in cancer, many miRNAs have
      been demonstrated to act as oncogenes, whereas others function as tumor
      suppressors. Furthermore, global miRNA dysregulation, due to alterations in miRNA
      processing factors, has been observed in a large variety of human cancer types.
      As previous studies have shown, the sequential miRNA processing can be divided
      into three steps: processing by RNAse in the nucleus; transportation by Exportin
      5 (XPO5) from the nucleus; and processing by the RNA-induced silencing complex
      (RISC) in the cytoplasm. Alteration in miRNA processing genes, by genomic
      mutations, aberrant expression or other means, could significantly affect cancer
      initiation, progression and metastasis. In this review, we focus on the
      biogenesis of miRNAs with emphasis on the potential of miRNA processing factors
      in human cancers. 

PMID- 26308069
TI  - Second-hand smoke - ignored implications.

PMID- 26308068
TI  - Chlorhexidine Gluconate, 4%, Showers and Surgical Site Infection Reduction.

PMID- 26308066
TI  - Functional Role of NBS1 in Radiation Damage Response and Translesion DNA
      Synthesis.
AB  - Nijmegen breakage syndrome (NBS) is a recessive genetic disorder characterized by
      increased sensitivity to ionizing radiation (IR) and a high frequency of
      malignancies. NBS1, a product of the mutated gene in NBS, contains several
      protein interaction domains in the N-terminus and C-terminus. The C-terminus of
      NBS1 is essential for interactions with MRE11, a homologous recombination repair
      nuclease, and ATM, a key player in signal transduction after the generation of
      DNA double-strand breaks (DSBs), which is induced by IR. Moreover, NBS1 regulates
      chromatin remodeling during DSB repair by histone H2B ubiquitination through
      binding to RNF20 at the C-terminus. Thus, NBS1 is considered as the first protein
      to be recruited to DSB sites, wherein it acts as a sensor or mediator of DSB
      damage responses. In addition to DSB response, we showed that NBS1 initiates
      Poleta-dependent translesion DNA synthesis by recruiting RAD18 through its
      binding at the NBS1 C-terminus after UV exposure, and it also functions after the
      generation of interstrand crosslink DNA damage. Thus, NBS1 has multifunctional
      roles in response to DNA damage from a variety of genotoxic agents, including IR.

PMID- 26308067
TI  - Determinants of Glycosaminoglycan (GAG) Structure.
AB  - Proteoglycans (PGs) are glycosylated proteins of biological importance at cell
      surfaces, in the extracellular matrix, and in the circulation. PGs are produced
      and modified by glycosaminoglycan (GAG) chains in the secretory pathway of animal
      cells. The most common GAG attachment site is a serine residue followed by a
      glycine (-ser-gly-), from which a linker tetrasaccharide extends and may continue
      as a heparan sulfate, a heparin, a chondroitin sulfate, or a dermatan sulfate GAG
      chain. Which type of GAG chain becomes attached to the linker tetrasaccharide is
      influenced by the structure of the protein core, modifications occurring to the
      linker tetrasaccharide itself, and the biochemical environment of the Golgi
      apparatus, where GAG polymerization and modification by sulfation and
      epimerization take place. The same cell type may produce different GAG chains
      that vary, depending on the extent of epimerization and sulfation. However, it is
      not known to what extent these differences are caused by compartmental
      segregation of protein cores en route through the secretory pathway or by
      differential recruitment of modifying enzymes during synthesis of different PGs.
      The topic of this review is how different aspects of protein structure, cellular
      biochemistry, and compartmentalization may influence GAG synthesis. 

PMID- 26308070
TI  - Disruption and inactivation of the PP2A complex promotes the proliferation and
      angiogenesis of hemangioma endothelial cells through activating AKT and ERK.
AB  - Hemangioma is a benign vascular neoplasm of unknown etiology. In this study, we
      generated an endothelial-specific PyMT gene-expressing transgenic mouse model
      that spontaneously develops hemangioma. Based on this transgenic model, a
      specific binding between PyMT and the core AC dimer of protein phosphatase 2A
      (PP2A) was verified in hemangioma vascular endothelial cells. The binding between
      PyMT and the PP2A AC dimer resulted in dissociation of the B subunit from the
      PP2A complex and inactivation of PP2A phosphatases, which in turn activated AKT
      and ERK signaling and promoted cell proliferation, migration and angiogenesis in
      vitro and tumorigenesis in vivo. Consistent with the in vitro findings, decreased
      PP2A phosphatase activity and disruption of the PP2A heterotrimeric complex were
      also observed in both primary transgene-positive TG(+) mouse hemangioma
      endothelial cells (TG(+) HEC cells) and human proliferating phase hemangioma
      endothelial (human HEC-P) cells, but not in transgene-negative TG(-) mouse normal
      vascular endothelial cells (TG(-) NEC cells) and human involuting phase
      hemangioma endothelial (human HEC-I) cells. Further, it was observed that in
      human hemangioma cells, endoglin could compete with the PP2A/A, C subunits for
      binding to the PP2A/B subunit, thereby resulting in dissociation of the B subunit
      from the PP2A complex. Treatment of Tie2/PyMT transgenic mice with the PP2A
      activator FTY720 significantly delayed the occurrence of hemangioma. Our data
      provide evidence of a previously unreported anti-proliferation and anti
      angiogenesis effect of PP2A in vascular endothelial cells, and show the
      therapeutic value of PP2A activators in hemangioma. 

PMID- 26308071
TI  - AMF/PGI-mediated tumorigenesis through MAPK-ERK signaling in endometrial
      carcinoma.
AB  - Autocrine motility factor (AMF), which is also known as phosphoglucose isomerase
      (PGI), enhances tumor cell growth and motility. In this study, we found that AMF
      and its receptor were both highly expressed in Endometrial Carcinoma (EC) tissues
      compared to normal tissues. Levels of AMF were increased in serum of endometrial
      cancer patients. Downregulation of AMF by shRNA inhibited invasion, migration and
      proliferation as well as growth in a three-dimensional culture. AMF cytokine
      function, but not enzymatic activity of PGI, regulated tumorigenic activities of
      AMF. The MAPK-ERK1/2 pathway contributed to AMF-induced effects in EC cells. In
      agreement, Mek inhibitor decreased AMF-induced invasion, migration and
      proliferation of EC cells. In addition, in two mouse tumor metastasis models (EC
      cells delivered through left ventricle or intraperitoneally) AMF-silenced EC
      cells showed decreased tumor proliferative and metastatic capacities. We suggest
      that AMF/PGI is a potential therapeutic target in endometrial carcinoma. 

PMID- 26308072
TI  - Elevated expression of UBE2T exhibits oncogenic properties in human prostate
      cancer.
AB  - Increased expression of ubiquitin-conjugating enzyme E2T (UBE2T) is reported in
      human prostate cancer. However, whether UBE2T plays any functional role in
      prostate cancer development remains unknown. We here report the first functional
      characterization of UBE2T in prostate carcinogenesis. Prostate cancer tissue
      array analysis confirmed upregulation of UBE2T in prostate cancer, especially
      these with distant metastasis. Moreover, higher level of UBE2T expression is
      associated with poorer prognosis of prostate cancer patients. Ectopic expression
      of UBE2T significantly promotes prostate cancer cell proliferation, motility and
      invasion, while UBE2T depletion by shRNA significantly inhibits these abilities
      of prostate cancer cells. Xenograft mouse model studies showed that
      overexpression of UBE2T promotes whereas UBE2T depletion inhibits tumor formation
      and metastasis significantly. Collectively, we identify critical roles of UBE2T
      in prostate cancer development and progression. These findings may serve as a
      framework for future investigations designed to more comprehensive determination
      of UBE2T as a potential therapeutic target. 

PMID- 26308073
TI  - Cysteine cathepsin activity suppresses osteoclastogenesis of myeloid-derived
      suppressor cells in breast cancer.
AB  - Cysteine cathepsin proteases contribute to many normal cellular functions, and
      their aberrant activity within various cell types can contribute to many
      diseases, including breast cancer. It is now well accepted that cathepsin
      proteases have numerous cell-specific functions within the tumor microenvironment
      that function to promote tumor growth and invasion, such that they may be valid
      targets for anti-metastatic therapeutic approaches. Using activity-based probes,
      we have examined the activity and expression of cysteine cathepsins in a mouse
      model of breast cancer metastasis to bone. In mice bearing highly metastatic
      tumors, we detected abundant cysteine cathepsin expression and activity in
      myeloid-derived suppressor cells (MDSCs). These immature immune cells have known
      metastasis-promoting roles, including immunosuppression and osteoclastogenesis,
      and we assessed the contribution of cysteine cathepsins to these functions.
      Blocking cysteine cathepsin activity with multiple small-molecule inhibitors
      resulted in enhanced differentiation of multinucleated osteoclasts. This
      highlights a potential role for cysteine cathepsin activity in suppressing the
      fusion of osteoclast precursor cells. In support of this hypothesis, we found
      that expression and activity of key cysteine cathepsins were downregulated during
      MDSC-osteoclast differentiation. Another cysteine protease, legumain, also
      inhibits osteoclastogenesis, in part through modulation of cathepsin L activity.
      Together, these data suggest that cysteine protease inhibition is associated with
      enhanced osteoclastogenesis, a process that has been implicated in bone
      metastasis. 

PMID- 26308074
TI  - Developing Cost-Effective Field Assessments of Carbon Stocks in Human-Modified
      Tropical Forests.
AB  - Across the tropics, there is a growing financial investment in activities that
      aim to reduce emissions from deforestation and forest degradation, such as REDD+.
      However, most tropical countries lack on-the-ground capacity to conduct reliable
      and replicable assessments of forest carbon stocks, undermining their ability to
      secure long-term carbon finance for forest conservation programs. Clear guidance
      on how to reduce the monetary and time costs of field assessments of forest
      carbon can help tropical countries to overcome this capacity gap. Here we provide
      such guidance for cost-effective one-off field assessments of forest carbon
      stocks. We sampled a total of eight components from four different carbon pools
      (i.e. aboveground, dead wood, litter and soil) in 224 study plots distributed
      across two regions of eastern Amazon. For each component we estimated survey
      costs, contribution to total forest carbon stocks and sensitivity to disturbance.
      Sampling costs varied thirty-one-fold between the most expensive component, soil,
      and the least, leaf litter. Large live stems (>=10 cm DBH), which represented
      only 15% of the overall sampling costs, was by far the most important component
      to be assessed, as it stores the largest amount of carbon and is highly sensitive
      to disturbance. If large stems are not taxonomically identified, costs can be
      reduced by a further 51%, while incurring an error in aboveground carbon
      estimates of only 5% in primary forests, but 31% in secondary forests. For rapid
      assessments, necessary to help prioritize locations for carbon- conservation
      activities, sampling of stems >=20cm DBH without taxonomic identification can
      predict with confidence (R2 = 0.85) whether an area is relatively carbon-rich or
      carbon-poor-an approach that is 74% cheaper than sampling and identifying all the
      stems >=10cm DBH. We use these results to evaluate the reliability of forest
      carbon stock estimates provided by the IPCC and FAO when applied to human
      modified forests, and to highlight areas where cost savings in carbon stock
      assessments could be most easily made. 

PMID- 26308075
TI  - Effects of p21 Gene Down-Regulation through RNAi on Antler Stem Cells In Vitro.
AB  - Cell cycle is an integral part of cell proliferation, and consists mainly of four
      phases, G1, S, G2 and M. The p21 protein, a cyclin dependent kinase inhibitor,
      plays a key role in regulating cell cyclevia G1 phase control. Cells capable of
      epimorphic regeneration have G2/M accumulation as their distinctive feature,
      whilst the majority of somatic cells rest at G1 phase. To investigate the role
      played byp21 in antler regeneration, we studied the cell cycle distribution of
      antler stem cells (ASCs), via down-regulation of p21 in vitro using RNAi. The
      results showed that ASCs had high levels of p21 mRNA expression and rested at G1
      phase, which was comparable to the control somatic cells. Down-regulation of p21
      did not result in ASC cell cycle re-distribution toward G2/M accumulation, but
      DNA damage and apoptosis of the ASCs significantly increased and the process of
      cell aging was slowed. These findings suggest that the ASCs may have evolved to
      use an alternative, p21-independent cell cycle regulation mechanism. Also a
      unique p21-dependent inhibitory effect may control DNA damage as a protective
      mechanism to ensure the fast proliferating ASCs do not become
      dysplastic/cancerous. Understanding of the mechanism underlying the role played
      by p21 in the ASCs could give insight into a mammalian system where epimorphic
      regeneration is initiated whilst the genome stability is effectively maintained. 

PMID- 26308076
TI  - When "In Your Face" Is Not Out of Place: The Effect of Timing of Disclosure of a
      Same-Sex Dating Partner under Conditions of Contact.
AB  - In a series of experiments we examined heterosexuals' reactions to the timing of
      disclosure of a gender-matched confederate's same-sex dating partner. Disclosure
      occurred in a naturalistic context-that is, it occurred when meeting, or
      expecting to soon meet, a same-sex attracted individual, who voluntarily shared
      this information with the participant as a natural part of a broader topic of
      discussion. The confederate, when disclosing early rather than later, was
      approached more closely (Prestudy) and liked more (Studies 1-2). Those
      experiencing early disclosure, compared with later, were less drawn to topics of
      lower intimacy (Study 1), were happier and more excited about meeting the
      confederate, and more likely to choose to be alone with the confederate for a one
      on-one discussion (Study 2). Further, women experiencing early disclosure were
      more willing to introduce the same-gender confederate to their friends (Study 2).
      The benefits of knowing sooner, rather than later, continued to apply even when
      participants were given further time to process the disclosure. To explore the
      underlying reasons for the more favorable experiences of upfront disclosure, we
      examined participants' memory of the information shared by the confederate (Study
      3). Results revealed that those who experienced delayed disclosure were more
      likely to incorrectly recall and negatively embellish information related to the
      confederate's sexual orientation, suggesting that early disclosure resulted in a
      reduced tendency to focus on the confederate's sexuality as a defining feature.
      These positive findings for early timing are discussed in light of previous
      studies that have found benefits for delayed disclosure and those that have
      failed to investigate the effects of timing of 'coming out' under conditions of
      contact. 

PMID- 26308077
TI  - Health Reporting in Print Media in Lebanon: Evidence, Quality and Role in
      Informing Policymaking.
AB  - BACKGROUND: Media plays a vital role in shaping public policies and opinions
      through disseminating health-related information. This study aims at exploring
      the role of media in informing health policies in Lebanon, identifying the
      factors influencing health reporting and investigating the role of evidence in
      health journalism and the quality of health reporting. It also identifies
      strategies to enhance the use of evidence in health journalism and improve the
      quality of health reporting. METHODS: Media analysis was conducted to assess the
      way media reports on health-related issues and the quality of reporting using a
      quality assessment tool. Semi-structured interviews were also conducted with 27
      journalists, researchers and policymakers to explore their perception on the role
      of media in health policymaking and the factors influencing health reporting. In
      addition, a validation workshop was conducted. RESULTS: Out of 1,279 health
      related news articles identified, 318 articles used certain type of evidence to
      report health issues 39.8% of which relied on experts' opinions as their source
      of evidence while only 5.9% referenced peer-reviewed research studies. The
      quality of health reporting was judged to be low based on a quality assessment
      tool consisting of a set of ten criteria. Journalists raised concerns about
      issues impeding them from referring to evidence. Journalists also reported
      difficulties with the investigative health journalism. Policymakers and
      researchers viewed media as an important tool for evidence-informed health
      policies, however, serious concerns were voiced in terms of the current practice
      and capacities. CONCLUSION: Our study provides a structured reflection on the
      role of media and the factors that influence health reporting including context
      specific strategies that would enhance the quality and promote the use of
      evidence in health reporting. In the light of the political changes in many
      Middle Eastern countries, findings from this study can contribute to redefining
      the role of media in strengthening health systems.

PMID- 26308078
TI  - Dent disease in children: diagnostic and therapeutic considerations.
AB  - BACKGROUND: Dent disease (DD) is a rare X-linked tubulopathy characterized by a
      proximal tubular dysfunction leading to nephrocalcinosis/nephrolithiasis and
      progressive renal failure. The disease is associated with a mutation either in
      CLCN5 or OCRL genes. We aim to define clinical and genetic disease
      characteristics and summarize treatments of Polish patients with DD. METHODS: The
      study cohort consists of 10 boys (aged 5 - 16.5 years) whose data were collected
      through POLtube Registry. RESULTS: All of the patients had tubular proteinuria,
      hypercalciuria, and nephrocalcinosis/nephrolithiasis. Renal impairment and growth
      deficiency were found in 3 patients and rickets in 2 patients. In total, 9 of 10
      patients carried a mutation in the CLCN5 gene. Five of 9 detected mutations were
      novel. In 1 patient with a clinical phenotype of DD, no mutations in either CLCN5
      or OCRL were discovered. Therapy consisted of thiazides in 7 patients, and
      phosphate supplements and enalapril in 3 cases. Growth hormone therapy was
      initiated in 3 patients and resulted in improved growth rate. CONCLUSIONS: We
      report clinical and molecular characterization of Polish children with DD. Our
      study suggests that this tubulopathy may be generally under-diagnosed in Poland.
      The study revealed variable treatments, demonstrating a need for therapeutic
      guidelines.

PMID- 26308079
TI  - Renal LECT2 amyloidosis: a newly described disorder gaining greater recognition.
AB  - Amyloidosis results from the pathologic deposition of beta pleated sheet fibrils
      within various organs including the kidney. Most often, the deposition is
      composed of the well-known monoclonal immunoglobulin light chains (AL) or serum
      amyloid A protein (AA). Recently, a new type of amyloidogenic protein was
      discovered, leukocyte chemotactic factor 2 (LECT2). This type of amyloid tends to
      have an affinity to kidney and liver and is recognized as a distinct clinico
      pathologic type of amyloidosis, presenting with varying degrees of impaired
      kidney function and proteinuria. Herein, a case of this uncommon novel
      amyloidosis is presented with a brief review of the literature. 

PMID- 26308080
TI  - Variable pharmacokinetics of extended interval tobramycin or gentamicin among
      critically ill patients undergoing continuous venovenous hemofiltration.
AB  - BACKGROUND/AIMS: Aminoglycosides are a major weapon against serious Gram-negative
      rod infections, yet aminoglycoside usage is limited by the risk of
      nephrotoxicity. The risk of toxicity is reduced by extended-interval dosing of
      aminoglycosides, defined as 5 - 7 mg/kg given intravenously in intervals of 24
      hours or greater based on serum drug concentrations. In critically ill patients
      undergoing continuous venovenous hemofiltration, there are few published reports
      of the pharmacokinetics of extended-interval dosing of aminoglycosides. METHODS:
      We evaluated the pharmacokinetics of extended-interval dosing of gentamicin and
      tobramycin in 9 critically ill patients on continuous venovenous hemofiltration
      at Dartmouth-Hitchcock Medical Center between April 2007 and September 2011.
      RESULTS: Aminoglycoside elimination half-life values were highly variable (median
      7 hours, range 3 - 26 hours) and did not correlate with total body weight or
      estimated creatinine clearance derived from the dose of continuous venovenous
      hemofiltration. Five of 9 patients cleared infection, but only 4 patients
      survived to hospital discharge, 2 of whom were dialysis-dependent. CONCLUSION:
      Extended interval aminoglycoside dosing during continuous venovenous
      hemofiltration yields unpredictable half-lives and drug levels among high-risk
      critically ill patients. Close monitoring of serum aminoglycoside levels is
      required.

PMID- 26308081
TI  - Anemia management practice patterns in small dialysis organizations following
      implementation of the prospective payment system.
AB  - BACKGROUND: The impact of the United States Prospective Payment System (PPS)
      "bundle payment system" on anemia management within small dialysis organizations
      (SDOs) was studied to evaluate the financia burden on SDOs. METHODS: Facilities
      enrolled in the original study on SDOs were grouped into three hemoglobin (Hb)
      categories by subject-months: > 25% of subjectmonths with Hb < 10 g/dL (sub-10);
      > 25% of subject-months with Hb > 12 g/dL (super-12); remaining facilities (10 -
      12 group). Subjectlevel data aggregated to facility level for Hb concentration,
      intravenous (IV) epoetin +/- (EA) dose per administration, dose titration, and EA
      administration frequency during the baseline and follow-up periods were
      described. RESULTS: Baseline demographic characteristics were imbalanced between
      the sub-10 (n = 7) and super-12 facilities (n = 5). Mean (SD) Hb concentrations
      were similar for sub-10 (11.1 (3.0) g/dL) and super-12 (11.6 (2.2) g/dL)
      facilities during the baseline period, but differed during the follow-up period
      (10.4 (2.7) vs. 11.4 (2.3) g/dL). The median (Q1, Q3) EA IV dose per
      administration during follow-up was 3,726 (3,467, 3,961) and 5,712 (4,816, 7,324)
      units in the sub-10 and super-12 facilities, respectively. A small trend toward
      upward titration was seen. CONCLUSIONS: Results suggest a difference in anemia
      management between sub-10 and super-12 facilities during the first year of PPS
      implementation. Future analyses evaluating patterns of reimbursement and shifts
      in clinical practice guidelines are warranted globally.

PMID- 26308082
TI  - Podocyte mRNA in the urinary sediment of minimal change nephropathy and focal
      segmental glomerulosclerosis.
AB  - BACKGROUND: Podocyte depletion is a characteristic feature of progressive renal
      failure. We hypothesize that studying the podocyte mRNA level in urinary sediment
      may provide diagnostic and prognostic information in adult nephrotic syndrome.
      METHODS: We studied 25 patients with minimal change nephropathy (MCN), 25 with
      focal segmental glomerulosclerosis (FSGS), and 17 healthy controls. The mRNA
      levels of nephrin, podocin, and synaptopodin in urinary sediment were quantified.
      RESULTS: There were significant differences in the urinary sediment nephrin and
      podocin, but not synaptopodin, mRNA levels between diagnosis groups. Post-hoc
      analysis further showed that urinary nephrin mRNA levels of the MCN group were
      lower than those in the control and FSGS groups, although the difference between
      MCN and FSGS groups did not reach statistical significance. The degree of
      proteinuria inversely correlated with urinary nephrin mRNA levels in the MCN (r =
      -0.526, p = 0.007) as well as in the FSGS group (r = -0.521, p = 0.008). For the
      FSGS group, the rate of renal function decline significantly correlated with
      baseline urinary synaptopodin mRNA levels (r = -0.496, p = 0.012). CONCLUSIONS:
      Urinary nephrin and podocin mRNA levels were reduced in patients with MCN and
      probably FSGS, and the magnitude of reduction correlated with the degree of
      proteinuria. Urinary synaptopodin mRNA levels correlated with the subsequent rate
      of renal function decline in patients with FSGS. Our result indicates that urine
      sediment podocyte mRNA levels provide novel insights in the pathophysiology of
      nephrotic syndrome and could be useful for risk stratification.

PMID- 26308083
TI  - One assay for all: exploring small molecule phosphorylation using amylose
      polyiodide complexes.
AB  - We present a generic method for screening small molecule kinases for their
      acceptor specificity. The release of the reaction byproduct adenosine diphosphate
      (ADP) triggers a concentration-dependent formation of amylose from sucrose, by
      using the combined enzymatic action of sucrose synthase and glycogen synthase.
      Kinase activities could be quantified photometrically after the formation of a
      dark-blue amylose-polyiodide complex. We demonstrate that this method can be used
      to profile both known and novel nucleotide- and sugar-kinases for their substrate
      specificity. Using a facile and widely available methodology, the amylose
      polyiodide small-molecule kinase assay presented herein has the potential to
      perform substrate screenings of small molecule kinases in a high-throughput
      manner. 

PMID- 26308084
TI  - Lack of Dietary Polyunsaturated Fatty Acids Causes Synapse Dysfunction in the
      Drosophila Visual System.
AB  - Polyunsaturated fatty acids (PUFAs) are essential nutrients for animals and
      necessary for the normal functioning of the nervous system. A lack of PUFAs can
      result from the consumption of a deficient diet or genetic factors, which impact
      PUFA uptake and metabolism. Both can cause synaptic dysfunction, which is
      associated with numerous disorders. However, there is a knowledge gap linking
      these neuronal dysfunctions and their underlying molecular mechanisms. Because of
      its genetic manipulability and its easy, fast, and cheap breeding, Drosophila
      melanogaster has emerged as an excellent model organism for genetic screens,
      helping to identify the genetic bases of such events. As a first step towards the
      understanding of PUFA implications in Drosophila synaptic physiology we designed
      a breeding medium containing only very low amounts of PUFAs. We then used the
      fly's visual system, a well-established model for studying signal transmission
      and neurological disorders, to measure the effects of a PUFA deficiency on
      synaptic function. Using both visual performance and eye electrophysiology, we
      found that PUFA deficiency strongly affected synaptic transmission in the fly's
      visual system. These defects were rescued by diets containing omega-3 or omega-6
      PUFAs alone or in combination. In summary, manipulating PUFA contents in the
      fly's diet was powerful to investigate the role of these nutrients on the fly's
      visual synaptic function. This study aims at showing how the first visual synapse
      of Drosophila can serve as a simple model to study the effects of PUFAs on
      synapse function. A similar approach could be further used to screen for genetic
      factors underlying the molecular mechanisms of synaptic dysfunctions associated
      with altered PUFA levels. 

PMID- 26308085
TI  - Risk Factors for HIV Infection among Young Thai Men during 2005-2009.
AB  - BACKGROUND: Thailand is one of several countries with a continuing generalized
      HIV epidemic. We evaluated the risk factors for HIV prevalence among 17-29 year
      old men conscripted by a random process into the Royal Thai Army (RTA) in 8
      cohorts from 2005-2009. METHODS: A series of case-cohort studies were conducted
      among the male RTA conscripts who had been tested for HIV seroprevalence after
      they were inducted. Men who were HIV positive were compared with a systematic
      random sample (1 in 30-40) of men from the total population of new conscripts.
      Each subject completed a detailed risk factor questionnaire. RESULTS: A total of
      240,039 young Thai men were conscripted into the RTA and were screened for HIV
      seroprevalence between November 2005 and May 2009. Of 1,208 (0.5%) HIV positive
      cases, 584 (48.3%) men were enrolled into the study. There were 7,396 men who
      were enrolled as a comparison group. Among conscripts who had an education lower
      than a college-level, the independent risk factors for HIV infection were age in
      years (AOR 1.38, 95% CI 1.28-1.48), a history of sex with another man (AOR 3.73,
      95% CI 2.70-5.13), HCV infection (AOR 3.89, 95% CI 2.56-5.90), and a history of
      sex with a female sex worker (FSW) (AOR 1.35, 95% CI 1.10-1.66). Among conscripts
      who had a college degree, the independent risk factor for HIV infection was a
      history of sex with another man (AOR 23.04, 95% CI 10.23-51.90). Numbers of
      sexual partners increased and the age at first sex, as well as the use of condoms
      for sex with a FSW decreased in successive cohorts. CONCLUSION: The HIV
      seroprevalence among cohorts of 17-29 years old men has remained at about 0.5%
      overall during 2005-2009. The most significant behavior associated with HIV
      prevalence was a history of sex with another man. Our data indicate continuing
      acquisition of HIV among young men in Thailand in recent years, especially among
      men with a history of same sex behavior.

PMID- 26308086
TI  - Accelerated Optical Projection Tomography Applied to In Vivo Imaging of
      Zebrafish.
AB  - Optical projection tomography (OPT) provides a non-invasive 3-D imaging modality
      that can be applied to longitudinal studies of live disease models, including in
      zebrafish. Current limitations include the requirement of a minimum number of
      angular projections for reconstruction of reasonable OPT images using filtered
      back projection (FBP), which is typically several hundred, leading to acquisition
      times of several minutes. It is highly desirable to decrease the number of
      required angular projections to decrease both the total acquisition time and the
      light dose to the sample. This is particularly important to enable longitudinal
      studies, which involve measurements of the same fish at different time points. In
      this work, we demonstrate that the use of an iterative algorithm to reconstruct
      sparsely sampled OPT data sets can provide useful 3-D images with 50 or fewer
      projections, thereby significantly decreasing the minimum acquisition time and
      light dose while maintaining image quality. A transgenic zebrafish embryo with
      fluorescent labelling of the vasculature was imaged to acquire densely sampled
      (800 projections) and under-sampled data sets of transmitted and fluorescence
      projection images. The under-sampled OPT data sets were reconstructed using an
      iterative total variation-based image reconstruction algorithm and compared
      against FBP reconstructions of the densely sampled data sets. To illustrate the
      potential for quantitative analysis following rapid OPT data acquisition, a
      Hessian-based method was applied to automatically segment the reconstructed
      images to select the vasculature network. Results showed that 3-D images of the
      zebrafish embryo and its vasculature of sufficient visual quality for
      quantitative analysis can be reconstructed using the iterative algorithm from
      only 32 projections-achieving up to 28 times improvement in imaging speed and
      leading to total acquisition times of a few seconds. 

PMID- 26308087
TI  - Cancer Visibility among Iranian Familial Networks: To What Extent Can We Rely on
      Family History Reports?
AB  - OBJECTIVE: Patients' unawareness of their cancer diagnosis (PUAW) and their
      tendency for non-disclosure (TTND) to relatives leads to a lack of cancer
      visibility among familial networks. Lack of familial cancer visibility could
      affect the accuracy of family cancer history (FCH) reports. In this study, we
      investigated familial cancer visibility and its potential determinants. PATIENTS
      AND METHODS: A sample of patients with a confirmed cancer diagnosis was
      interviewed. Participants were asked about their number of relatives, number of
      their relatives who are aware about the cancer diagnosis, and the number of
      relatives from whom they intended to conceal their diagnosis. PUAW was also
      assessed. Point estimates and 95% confidence intervals were calculated using the
      bootstrap technique. Multivariate analyses were conducted using mixed Poisson and
      logistic regression analyses. RESULTS: A total of 415 participants with a mean
      age of 53+/-15 years and a male to female ratio of 0.53 were enrolled in this
      study. The rates of PUAW, TTND, and familial cancer visibility in the total
      sample were 0.20 (95% confidence interval (CI): 0.16, 0.24), 0.16 (95% CI: 0.12,
      0.19), and 0.86 (95% CI: 0.83, 0.89), respectively. PUAW (adjusted rate ratio
      (RR) = 1.32, 95% CI: 1.27, 1.38), TTND (RR = 0.92, 95% CI: 0.91, 0.93), and the
      patients' gender (RR = 0.92, 95% CI: 0.82, 0.95) were the most important
      determinants of familial cancer visibility. CONCLUSION: Familial cancer
      visibility may be a point of concern among the Iranian population. Self-reported
      cancer histories and FCHs may have low sensitivities (not exceeding 80% and 86%,
      respectively) in this population. However, these estimates may vary across
      different societies, because of societal and cultural contexts.

PMID- 26308088
TI  - Quality of Life of People Living with HIV/AIDS: A Cross-Sectional Study in
      Zhejiang Province, China.
AB  - Health-related quality of life (HRQOL) has become a concept commonly used in the
      related research. Using the World Health Organization Quality of Life
      Questionnaire for Brief Version (WHOQOL-BREF), this study evaluated the Quality
      of Life (QOL) of people living with HIV/AIDS (PLWHA) in Zhejiang province, China,
      and assessed the influences of demographic, laboratory and disease-related
      variables on QOL. This cross-sectional study was conducted among PLWHA aged >= 18
      years in Taizhou municipality, Zhejiang province, China, between August 1 and
      October 31, 2014. A multiple linear regression model was used to analyze the
      influential factors. Of 403 subjects, 72.48% were male, 72.46% had received a
      high- school or above education, 94.79% were of Han ethnicity, and 65.51% were
      non farmers. The total score of QOL was 15.99+/-1.99. The scores of QOL in
      physiological, psychological, social relation, and environmental domains were
      14.99 +/-2.25, 14.25 +/-2.12, 13.22 +/-2.37, and 13.31 +/-1.99 respectively.
      Except the total score of QOL and the score of environmental domain (p<0.05), the
      scores in other domains had no significant difference with the results of the
      national norm level. The multiple linear regression model identified the physical
      domain related factors to be age (beta = -0.045), CD4 count (beta = 0.002), and
      ART adherence(beta = 1.231). And it also showed that psychological domain related
      factors included CD4 count (beta = 0.002) and WHO clinical stage (beta = -0.437);
      social domain related factors included WHO clinical stage (beta = -0.704) and ART
      adherence (beta = 1.177); while environmental domain related factors included WHO
      clinical stage (beta = -0.538), educational status(beta = 0.549) and ART
      adherence(beta = 1.078).Those who are young, with higher level of education,
      higher CD4 count and good access and adherence of ART, are likely to have better
      QOL among PLWHA in Zhejiang province. This suggests that in addition to ART, many
      other factors should be taken into consideration to improve the QOL of PLWHA. The
      relatively lower scores the subjects received in social relation and
      environmental domains also suggest that social relation and environmental
      interventions need to be strengthened. 

PMID- 26308090
TI  - The Response to and Recovery From Maximum-Strength and -Power Training in Elite
      Track and Field Athletes.
AB  - There is a great deal of research on the responses to resistance training;
      however, information on the responses to strength and power training conducted by
      elite strength and power athletes is sparse. PURPOSE: To establish the acute and
      24-h neuromuscular and kinematic responses to Olympic-style barbell strength and
      power exercise in elite athletes. METHODS: Ten elite track and field athletes
      completed a series of 3 back-squat exercises each consisting of 4 * 5
      repetitions. These were done as either strength or power sessions on separate
      days. Surface electromyography (sEMG), bar velocity, and knee angle were
      monitored throughout these exercises and maximal voluntary contraction (MVC),
      jump height, central activation ratio (CAR), and lactate were measured pre, post,
      and 24 h thereafter. RESULTS: Repetition duration, impulse, and total work were
      greater (P < .01) during strength sessions, with mean power being greater (P <
      .01) after the power sessions. Lactate increased (P < .01) after strength but not
      power sessions. sEMG increased (P < .01) across sets for both sessions, with the
      strength session increasing at a faster rate (P < .01) and with greater
      activation (P < .01) by the end of the final set. MVC declined (P < .01) after
      the strength and not the power session, which remained suppressed (P < .05) 24 h
      later, whereas CAR and jump height remained unchanged. CONCLUSION: A greater
      neuromuscular and metabolic demand after the strength and not power session is
      evident in elite athletes, which impaired maximal-force production for up to 24
      h. This is an important consideration for planning concurrent athlete training.

PMID- 26308089
TI  - Prenatal Phthalate Exposures and Childhood Fat Mass in a New York City Cohort.
AB  - BACKGROUND: Experimental animal studies and limited epidemiologic evidence
      suggest that prenatal exposure to phthalates may be obesogenic, with potential
      sex-specific effects of phthalates having anti-androgenic activity. OBJECTIVES:
      We aimed to assess associations between prenatal phthalate exposures and
      childhood fat mass in a prospective cohort study. METHODS: We measured phthalate
      metabolite concentrations in third-trimester maternal urine in a cohort of women
      enrolled in New York City between 1998 and 2002 (n = 404). Among 180 children (82
      girls and 98 boys), we evaluated body composition using a Tanita scale at
      multiple follow-up visits between ages 4 and 9 years (363 total visits). We
      estimated associations of standard deviation differences or tertiles of natural
      log phthalate metabolite concentrations with percent fat mass using linear mixed
      effects regression models with random intercepts for repeated outcome
      measurements. We assessed associations in multiple metabolite models and adjusted
      for covariates including prepregnancy body mass index, gestational weight gain,
      maternal smoking during pregnancy, and breastfeeding. RESULTS: We did not observe
      associations between maternal urinary phthalate concentrations and percent body
      fat in models examining continuous exposures. Fat mass was 3.06% (95% CI: -5.99, 
      0.09%) lower among children in the highest tertile of maternal urinary
      concentrations of summed di(2-ethylhexyl) phthalate (SigmaDEHP) metabolites than
      in children in the lowest tertile. Though estimates were imprecise, there was
      little evidence that associations between maternal urinary phthalate
      concentrations and percent fat mass were modified by child's sex. CONCLUSIONS:
      Prenatal phthalate exposures were not associated with increased body fat among
      children 4-9 years of age, though high prenatal DEHP exposure may be associated
      with lower fat mass in childhood. CITATION: Buckley JP, Engel SM, Mendez MA,
      Richardson DB, Daniels JL, Calafat AM, Wolff MS, Herring AH. 2016. Prenatal
      phthalate exposures and childhood fat mass in a New York City cohort. Environ
      Health Perspect 124:507-513; http://dx.doi.org/10.1289/ehp.1509788.

PMID- 26308091
TI  - Association of Insulin Resistance, Arterial Stiffness and Telomere Length in
      Adults Free of Cardiovascular Diseases.
AB  - BACKGROUND: Chronic inflammation and oxidative stress might be considered the key
      mechanisms of aging. Insulin resistance (IR) is a phenomenon related to
      inflammatory and oxidative stress. We tested the hypothesis that IR may be
      associated with cellular senescence, as measured by leukocyte telomere length
      (LTL), and arterial stiffness (core feature of arterial aging), as measured by
      carotid-femoral pulse wave velocity (c-f PWV). METHODS: The study group included
      303 subjects, mean age 51.8 +/-13.3 years, free of known cardiovascular diseases
      and regular drug consumption. For each patient, blood pressure was measured,
      blood samples were available for biochemical parameters, and LTL was analyzed by
      real time q PCR. C-f PWV was measured with the help of SphygmoCor. SAS 9.1 was
      used for statistical analysis. RESULTS: Through multiple linear regression
      analysis, c-f PWV is independently and positively associated with age (p =
      0.0001) and the homeostasis model assessment of insulin resistance (HOMA-IR; p =
      0.0001) and independently negatively associated with LTL (p = 0.0378). HOMA-IR
      seems to have a stronger influence than SBP on arterial stiffness. In all
      subjects, age, HOMA-IR, LTL, and SBP predicted 32% of the variance in c-f PWV.
      LTL was inversely associated with HOMA-IR (p = 0.0001) and age (p = 0.0001). In
      all subjects, HOMA-IR, age, sex, and SBP predicted 16% of the variance in LTL.
      CONCLUSIONS: These data suggest that IR is associated with cell senescence and
      arterial aging and could, therefore, become the main target in preventing
      accelerated arterial aging, besides blood pressure control. Research in telomere
      biology may reveal new ways of estimating cardiovascular aging and risk.

PMID- 26308093
TI  - Correction: Rapid Diversity Loss of Competing Animal Species in Well-Connected
      Landscapes.

PMID- 26308092
TI  - Dance and Music in "Gangnam Style": How Dance Observation Affects Meter
      Perception.
AB  - Dance and music often co-occur as evidenced when viewing choreographed dances or
      singers moving while performing. This study investigated how the viewing of dance
      motions shapes sound perception. Previous research has shown that dance reflects
      the temporal structure of its accompanying music, communicating musical meter
      (i.e. a hierarchical organization of beats) via coordinated movement patterns
      that indicate where strong and weak beats occur. Experiments here investigated
      the effects of dance cues on meter perception, hypothesizing that dance could
      embody the musical meter, thereby shaping participant reaction times (RTs) to
      sound targets occurring at different metrical positions.In experiment 1,
      participants viewed a video with dance choreography indicating 4/4 meter (dance
      condition) or a series of color changes repeated in sequences of four to indicate
      4/4 meter (picture condition). A sound track accompanied these videos and
      participants reacted to timbre targets at different metrical positions.
      Participants had the slowest RT's at the strongest beats in the dance condition
      only. In experiment 2, participants viewed the choreography of the horse-riding
      dance from Psy's "Gangnam Style" in order to examine how a familiar dance might
      affect meter perception. Moreover, participants in this experiment were divided
      into a group with experience dancing this choreography and a group without
      experience. Results again showed slower RTs to stronger metrical positions and
      the group with experience demonstrated a more refined perception of metrical
      hierarchy. Results likely stem from the temporally selective division of
      attention between auditory and visual domains. This study has implications for
      understanding: 1) the impact of splitting attention among different sensory
      modalities, and 2) the impact of embodiment, on perception of musical meter.
      Viewing dance may interfere with sound processing, particularly at critical
      metrical positions, but embodied familiarity with dance choreography may
      facilitate meter awareness. Results shed light on the processing of multimedia
      environments. 

PMID- 26308094
TI  - Engaging with Community Researchers for Exposure Science: Lessons Learned from a
      Pesticide Biomonitoring Study.
AB  - A major challenge in biomonitoring studies with members of the general public is
      ensuring their continued involvement throughout the necessary length of the
      research. The paper presents evidence on the use of community researchers,
      recruited from local study areas, as a mechanism for ensuring effective
      recruitment and retention of farmer and resident participants for a pesticides
      biomonitoring study. The evidence presented suggests that community researchers'
      abilities to build and sustain trusting relationships with participants enhanced
      the rigour of the study as a result of their on-the-ground responsiveness and
      flexibility resulting in data collection beyond targets expected. 

PMID- 26308095
TI  - Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue
      Semaglutide.
AB  - Liraglutide is an acylated glucagon-like peptide-1 (GLP-1) analogue that binds to
      serum albumin in vivo and is approved for once-daily treatment of diabetes as
      well as obesity. The aim of the present studies was to design a once weekly GLP-1
      analogue by increasing albumin affinity and secure full stability against
      metabolic degradation. The fatty acid moiety and the linking chemistry to GLP-1
      were the key features to secure high albumin affinity and GLP-1 receptor (GLP-1R)
      potency and in obtaining a prolonged exposure and action of the GLP-1 analogue.
      Semaglutide was selected as the optimal once weekly candidate. Semaglutide has
      two amino acid substitutions compared to human GLP-1 (Aib(8), Arg(34)) and is
      derivatized at lysine 26. The GLP-1R affinity of semaglutide (0.38 +/- 0.06 nM)
      was three-fold decreased compared to liraglutide, whereas the albumin affinity
      was increased. The plasma half-life was 46.1 h in mini-pigs following i.v.
      administration, and semaglutide has an MRT of 63.6 h after s.c. dosing to mini
      pigs. Semaglutide is currently in phase 3 clinical testing. 

PMID- 26308096
TI  - Emotion perception from a componential perspective.
AB  - The common conceptual understanding of emotion is that they are multi
      componential, including subjective feelings, appraisals, psychophysiological
      activation, action tendencies, and motor expressions. Emotion perception,
      however, has traditionally been studied in terms of emotion labels, such as
      "happy", which do not clearly indicate whether one, some, or all emotion
      components are perceived. We examine whether emotion percepts are multi
      componential and extend previous research by using more ecologically valid,
      dynamic, and multimodal stimuli and an alternative response measure. The results
      demonstrate that observers can reliably infer multiple types of information
      (subjective feelings, appraisals, action tendencies, and social messages) from
      complex emotion expressions. Furthermore, this finding appears to be robust to
      changes in response items. The results are discussed in light of their
      implications for research on emotion perception.

PMID- 26308097
TI  - Catalytic Kinetic Resolution of Disubstituted Piperidines by Enantioselective
      Acylation: Synthetic Utility and Mechanistic Insights.
AB  - The catalytic kinetic resolution of cyclic amines with achiral N-heterocyclic
      carbenes and chiral hydroxamic acids has emerged as a promising method to obtain
      enantio-enriched amines with high selectivity factors. In this report, we
      describe the catalytic kinetic resolution of disubstituted piperdines with
      practical selectivity factors (s, up to 52) in which we uncovered an unexpected
      and pronounced conformational effect resulting in disparate reactivity and
      selectivity between the cis- and trans-substituted piperidine isomers. Detailed
      experimental and computational studies of the kinetic resolution of various
      disubstituted piperidines revealed a strong preference for the acylation of
      conformers in which the alpha-substituent occupies the axial position. This work
      provides further experimental and computational support for the concerted 7
      member transition state model for acyl transfer reagents and expands the scope
      and functional group tolerance of the secondary amine kinetic resolution. 

PMID- 26308098
TI  - Highly Efficient Dual-Color Electrochemiluminescence from BODIPY-Capped PbS
      Nanocrystals.
AB  - Electrochemiluminescence (ECL) of a hybrid system consisting of PbS nanocrystals
      (NCs) and a BODIPY dye (BDY) capping ligand was discovered to produce highly
      efficient dual emissions with tri-n-propylamine as a coreactant. By means of
      spooling ECL spectroscopy, the strong dual ECL emission peaks of 984 and 680 nm
      were attributed to the PbS and BDY moieties, respectively, and found to be
      simultaneous during the light evolution and devolution. The ECL of the PbS was
      enhanced via NC collisions with the electrode and reached an efficiency of 96%
      relative to that of Ru(bpy)3(2+), which is the highest among the semiconductor
      NCs. 

PMID- 26308099
TI  - In Situ Detection of Subsurface Biofilm Using Low-Field NMR: A Field Study.
AB  - Subsurface biofilms are central to bioremediation of chemical contaminants in
      soil and groundwater whereby micro-organisms degrade or sequester environmental
      pollutants like nitrate, hydrocarbons, chlorinated solvents and heavy metals.
      Current methods to monitor subsurface biofilm growth in situ are indirect.
      Previous laboratory research conducted at MSU has indicated that low-field
      nuclear magnetic resonance (NMR) is sensitive to biofilm growth in porous media,
      where biofilm contributes a polymer gel-like phase and enhances T2 relaxation.
      Here we show that a small diameter NMR well logging tool can detect biofilm
      accumulation in the subsurface using the change in T2 relaxation behavior over
      time. T2 relaxation distributions were measured over an 18 day experimental
      period by two NMR probes, operating at approximately 275 kHz and 400 kHz,
      installed in 10.2 cm wells in an engineered field testing site. The mean log T2
      relaxation times were reduced by 62% and 43%, respectively, while biofilm was
      cultivated in the soil surrounding each well. Biofilm growth was confirmed by
      bleaching and flushing the wells and observing the NMR signal's return to
      baseline. This result provides a direct and noninvasive method to
      spatiotemporally monitor biofilm accumulation in the subsurface. 

PMID- 26308100
TI  - High-Performance Silicon Battery Anodes Enabled by Engineering Graphene
      Assemblies.
AB  - We propose a novel material/electrode design formula and develop an engineered
      self-supporting electrode configuration, namely, silicon nanoparticle impregnated
      assemblies of templated carbon-bridged oriented graphene. We have demonstrated
      their use as binder-free lithium-ion battery anodes with exceptional lithium
      storage performances, simultaneously attaining high gravimetric capacity (1390
      mAh g(-1) at 2 A g(-1) with respect to the total electrode weight), high
      volumetric capacity (1807 mAh cm(-3) that is more than three times that of
      graphite anodes), remarkable rate capability (900 mAh g(-1) at 8 A g(-1)),
      excellent cyclic stability (0.025% decay per cycle over 200 cycles), and
      competing areal capacity (as high as 4 and 6 mAh cm(-2) at 15 and 3 mA cm(-2),
      respectively). Such combined level of performance is attributed to the templated
      carbon bridged oriented graphene assemblies involved. This engineered graphene
      bulk assemblies not only create a robust bicontinuous network for rapid transport
      of both electrons and lithium ions throughout the electrode even at high material
      mass loading but also allow achieving a substantially high material tap density
      (1.3 g cm(-3)). Coupled with a simple and flexible fabrication protocol as well
      as practically scalable raw materials (e.g., silicon nanoparticles and graphene
      oxide), the material/electrode design developed would propagate new and viable
      battery material/electrode design principles and opportunities for energy storage
      systems with high-energy and high-power characteristics. 

PMID- 26308101
TI  - Short-term persistence of oculomotor rehabilitative changes in mild traumatic
      brain injury (mTBI): A pilot study of clinical effects.
AB  - PRIMARY OBJECTIVE: In our earlier published studies, oculomotor therapy (OMT) was
      performed in 15 individuals with mild traumatic brain injury (mTBI) and over 90%
      of the clinical oculomotor parameters abnormal at baseline significantly improved
      immediately following the OMT. There was no placebo (P) effect on any of the
      parameters. The purpose of the present pilot study was to assess the short-term
      persistence of the previously obtained positive OMT findings. RESEARCH DESIGN:
      Upon completion of the OMT, clinical oculomotor parameters were re-assessed at 3
      month and 6-month periods. No subsequent training was performed during this 6
      month period. METHODS AND PROCEDURES: Clinical measures were repeated in eight of
      the 15 subjects who subsequently completed both the 3-month and 6-month follow-up
      assessments. All measures were assessed using conventional clinical testing
      methods. MAIN OUTCOMES AND RESULTS: Eight of the 13 (62%) clinical oculomotor
      parameters exhibited either persistence of, or delayed, improvement at the 3 and
      6 month follow-up intervals. CONCLUSIONS: Findings demonstrate both the presence
      and persistence of oculomotor-based changes, suggestive of neural plasticity even
      in the adult, compromised brain. Further studies are warranted to confirm and
      extend the present pilot findings.

PMID- 26308102
TI  - Functionalizing Titanium Disilicide Nanonets with Cobalt Oxide and Palladium for
      Stable Li Oxygen Battery Operations.
AB  - Li oxygen (Li-O2) batteries promise high energy densities but suffer from
      challenges such as poor cycling lifetime and low round-trip efficiencies.
      Recently, the instability of carbon cathode support has been recognized to
      contribute significantly to the problems faced by Li-O2 batteries. One strategy
      to address the challenge is to replace carbon materials with carbon-free ones.
      Here, we present titanium silicide nanonets (TiSi2) as such a new material
      platform for this purpose. Because TiSi2 exhibits no oxygen reduction reaction
      (ORR) or oxygen evolution reaction (OER) activities, catalysts are required to
      promote discharge and recharge reactions at reduced overpotentials. Pd
      nanoparticles grown by atomic layer deposition (ALD) were observed to provide the
      bifunctionalities of ORR and OER. Their adhesion to TiSi2 nanonets, however, was
      found to be poor, leading to drastic performance decay due to Pd detachments and
      aggregation. The problem was solved by adding another layer of Co3O4, also
      prepared by ALD. Together, the Pd/Co3O4/TiSi2 combination affords the desired
      functionalities and stability. Li-O2 test cells that lasted more than 126 cycles
      were achieved. The reversible formation and decomposition of Li2O2 was verified
      by Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), ferrocenium back
      titration, and gas-chromatography and mass spectrometry (GC-MS). Our results
      provide a new material platform for detailed studies of Li-O2 operations for
      better understanding of the chemistries involved, which is expected to help pave
      the way toward practical Li-O2 battery realizations. 

PMID- 26308103
TI  - Autoimmune thyroid dysfunction after allogeneic hematopoietic stem cell
      transplant.

PMID- 26308104
TI  - Long-Term Changes of Macular Thickness after Pars Plana Vitrectomy in Optic Disc
      Pit Maculopathy: A Spectral-Domain Optical Coherence Tomography Study.
AB  - PURPOSE: To evaluate macular thickness (MT) changes, using spectral domain
      optical coherence tomography (SD-OCT) in patients with optic disc pit (ODP)
      maculopathy after pars plana vitrectomy (PPV) with or without internal limiting
      membrane (ILM) peeling. PROCEDURES: Our retrospective study included nine
      patients with ODP maculopathy, treated with either PPV (n = 5) or PPV with ILM
      peeling (n = 4). All participants, who had a mean long-term follow-up of 33.4 +/-
      7.0 months, underwent a complete ophthalmological examination and SD-OCT. Due to
      the preoperative macular elevation, the postoperative MT in the operated patients
      was compared with that of fellow eyes and with normative data. RESULTS: A
      significant reduction in MT was noticed in all macular sectors of the operated
      cases at the last examination. The reduction was more evident in the group of PPV
      with ILM peeling. At the last examination of the follow-up, there was a
      statistically significant improvement regarding BCVA in both groups in comparison
      with baseline, while the two groups did not differ significantly in between (p =
      0.245). CONCLUSIONS: In the long-term follow-up period, our study demonstrated a
      significant reduction in MT in patients with ODP maculopathy treated with PPV,
      which was more profound in those cases where PPV included ILM peeling. .

PMID- 26308105
TI  - Expression and DNA methylation status of the Rap2B gene in human bronchial
      epithelial cells treated by cigarette smoke condensate.
AB  - BACKGROUND: The relationship between lung cancer and smoking has been
      demonstrated. The Rap2B gene is usually overexpressed in lung cancers. This study
      was aimed to investigate the Rap2B gene expression and its promoter methylation
      in human bronchial epithelial cells (16HBE) treated by cigarette smoke condensate
      (CSC). METHODS: 16HBE cells were treated with CSC (1/8 IC50). Soft ager assay,
      tumorigenicity test, chromosome aberrations analysis were used to identify the
      transformed cells. The expression level of mRNA and protein of Rap2B was detected
      using real time PCR and Western blotting, respectively. The genome DNA
      methylation level was detected using combined bisulfite restriction analysis
      (COBRA) and the methylation status of the target fragment in Rap2B gene promoter
      was determined by bisulfite sequencing PCR (BSP). RESULTS: The 16HBE cells were
      successfully malignant transformed after the chronic exposure to CSC. The
      expression of Rap2B gradually increased in the process of malignant
      transformation. Meanwhile, global DNA was hypomethylated. However, no obvious
      change was observed in the methylation level of Rap2B gene promoter in
      transformed 16HBE cells. CONCLUSIONS: Rap2B gene may play an important role in
      the process of lung cancer and global DNA hypomethylation might be an early event
      in tumorigenesis.

PMID- 26308106
TI  - Evaluation of soft tissue changes around the lips after bracket debonding using
      three-dimensional stereophotogrammetry.
AB  - OBJECTIVE: To evaluate the changes in soft tissue around the lips after
      orthodontic bracket debonding using three-dimensional (3-D) stereophotogrammetry.
      MATERIALS AND METHODS: 3-D facial images of 20 subjects (10 men and 10 women;
      mean age, 26.81 +/- 7.23 years) were taken with a white light scanner before and
      after debonding the labial brackets. Two images acquired from each subject were
      superimposed, and 15 soft tissue landmarks around the lips were plotted and
      analyzed. Statistical analysis was performed using both paired and independent t
      tests (P < .05). RESULTS: There were no significant changes in position of any
      landmark on the x (left-right)- or y (vertical)-axes after removal of the
      brackets. However, the landmarks in the oral commissures and lower lip (LLP, 
      0.55 mm; Li, -0.44 mm; Ch-L, -0.56 mm, all P < .05) on the z (anteroposterior)
      axis showed statistically significant differences. There were no significant
      positional changes of most landmarks on the x-, y-, or z- axes after bracket
      removal among the various genders and lip thicknesses. CONCLUSIONS: There was a
      slight retrusion in the oral commissure and lower lip areas after debonding, but
      no changes were found in the upper lip area. This study showed that 3-D
      stereophotogrammetry can be useful in evaluating facial soft tissue changes in
      orthodontic patients.

PMID- 26308107
TI  - The Gift of Mentorship.

PMID- 26308108
TI  - Re: Vibratory stimulation increases interleukin-1 beta secretion during
      orthodontic tooth movement. Chidchanok Leethanakul; Sumit Suamphan; Suwanna
      Jitpukdeebodintra; Udom Thongudomporn; Chairat Charoemratrote. The Angle
      Orthodontist. 2015, Online Early.

PMID- 26308109
TI  - Re: Response to: Vibratory stimulation increases interleukin-1 beta secretion
      during orthodontic tooth movement. Chidchanok Leethanakul; Sumit Suamphan;
      Suwanna Jitpukdeebodintra; Udom Thongudomporn; Chairat Charoemratrote. The Angle
      Orthodontist. 2015, Online Early.

PMID- 26308110
TI  - Erratum.

PMID- 26308112
TI  - Concomitant use of VAQTA with PedvaxHIB and Infanrix in 12 to 17 month old
      children.
AB  - Open-label, multicenter, randomized study (NCT00289913) evaluated immunogenicity,
      safety, and tolerability of Vaqta (hepatitis A vaccine) administered with
      PedvaxHIB (Haemophilus b conjugate vaccine [Meningococcal protein conjugate]) &
      Infanrix (diphtheria/tetanus/acellular pertussis vaccine) in healthy, 15-month
      old children. Five groups were evaluated: Group 1 received Vaqta/Infanrix
      PedvaxHIB on Day-1 and Vaqta at Week-24; Group 2 received Infanrix PedvaxHIB on
      Day-1, Vaqta at Week-4, and Vaqta at Week-28; Group 3 received Vaqta/PedvaxHIB on
      Day-1 and Vaqta Week-24; Group 4 received PedvaxHIB on Day-1, Vaqta at Week-4,
      and Vaqta at Week-28; and Group 5 (safety only) received Vaqta on Day-1 and Vaqta
      at Week-24. Hepatitis A seropositivity rate (SPR: >=10 mIU/mL), Hib capsular
      polyribosylribitol phosphate (PRP) antibody response (>1.0 MUg/mL), and geometric
      mean titers (GMT) to pertussis toxin (PT), pertussis filamentous hemagglutinin
      antibody (FHA), and pertactin were examined. Non-inferiority statistical criteria
      required a difference >10% in Hepatitis A SPR, PRP >1.0 MUg/mL, and a GMT ratio
      of >0.67 for pertussis antigens. Injection-site and systemic adverse events (AEs)
      and daily temperatures were collected. Hepatitis A SPRs were 100% for Groups 1-4,
      regardless of initial serostatus. Anti-PRP titers were comparable (98.1% - 97.0%)
      for Groups 1-4. GMT and mean fold-rise were comparable for all 3 pertussis
      antigen components between concomitant and nonconcomitant groups. Criteria for
      non-inferiority of immune responses for concomitant vs nonconcomitant
      administration were met for Hepatitis A, Hib, and pertussis antigens. No
      statistically significant incidence differences of individual AEs were found
      between concomitant and nonconcomitant groups. No serious vaccine-related AEs or
      deaths were reported; no subject discontinued due to an AE. Immune responses to
      Vaqta, PedvaxHIB, and Infanrix given concomitantly were non-inferior to
      nonconcomitant responses. Vaqta administered with PedvaxHIB & Infanrix had an
      acceptable safety profile in 15-month-old children.

PMID- 26308113
TI  - Clinical characteristics and laboratory findings in Danish children hospitalized
      with primary Epstein-Barr virus infection.
AB  - BACKGROUND: Epstein-Barr virus (EBV) positive infectious mononucleosis (IM) is a
      common disease in adolescents. However, IM is often considered a rare disease in
      early childhood. We aimed to describe the classical presentation of adolescent
      EBV-associated IM compared to EBV infection at younger age. METHODS: All
      immunocompetent children hospitalized at Hvidovre University Hospital, Copenhagen
      between 2002 and 2013, who presented with clinical features that prompted a
      laboratory test for EBV, and who tested positive by presence of EBV-specific
      antibodies, heterophile antibodies or a positive EBV PCR were included (n = 95).
      RESULTS: Children aged 1-2 years were the age group most commonly hospitalized
      with acute EBV infection (27% of the cohort), followed by teenagers aged 14-15
      years (23%). Fever, cervical lymphadenopathy, tonsillitis and fatigue were the
      most common physical findings overall. Dividing the children into three age
      groups (0-4 years, 5-10 years and 11-15 years) revealed that the oldest age
      groups significantly more often suffered from headache, tonsillitis, sore throat,
      abdominal pain and nausea. Young children typically presented with a runny nose,
      fever, fatigue and cervical adenitis. Compared with children under 5, children
      aged 5-15 years more often showed lymphocytosis (84% vs 62%), elevated alanine
      aminotransferase (77% vs 33%) and lactate dehydrogenase (79% vs 44%). CONCLUSION:
      EBV infection is common in young children, and children less than 3 years of age
      constitute the largest group of hospitalizations for acute EBV infection. EBV
      associated IM should be suspected in febrile children of all ages with
      tonsillitis, lymphadenopathy, lymphocytosis and elevated liver enzymes.

PMID- 26308114
TI  - Synthesis and biological activity of ester derivatives of mycophenolic acid and
      acridines/acridones as potential immunosuppressive agents.
AB  - Improved derivatives of mycophenolic acid (MPA) are necessary to reduce the
      frequency of adverse effects, this drug exerts in treated patients. In this
      study, MPA was coupled with N-(omega-hydroxyalkyl)-9-acridone-4-carboxamides or N
      (omega-hydroxyalkyl)acridine-4-carboxamides to give respective ester conjugates
      upon Yamaguchi protocol. This esterification required protection of phenol group
      in MPA. Designed conjugates revealed higher potency in vitro than parent MPA.
      Acridine derivatives were more active than acridone analogs and length of the
      alkyl linker between MPA and heterocyclic units influenced the observed
      cytotoxicity. Derivatives 2b, 2d, 3a, 3b displayed the most promising
      immunosuppressive activity. 

PMID- 26308115
TI  - Injury prevention in a self-learning health system.

PMID- 26308116
TI  - Toward a centralized database for child safety centers: Results of a feasibility
      pilot study.
AB  - BACKGROUND: Safety centers (SCs) are hospital-affiliated outlets that provide
      families with safety products and personalized education about preventing
      injuries. Roughly 40 SCs are in operation across the United States, but no single
      model for staffing, supplying, or sustaining them has emerged. The project aimed
      to determine the feasibility of a centralized database for SC evaluation as the
      first step toward growing this proven intervention. METHODS: An Expert Advisory
      Committee was convened to determine data collection elements and procedures.
      Representatives from nine hospital-based SCs collected data about car seat and
      bike helmet sales and education provided between August 1, 2013, to December 31,
      2013. RESULTS: A total of 645 study-related safety products were distributed at
      cost (72%), below cost (10%), or for free (19%). Education was provided for 96%
      of all products distributed, including receipt of print materials (81%) and
      product demonstrations (83%). Visitors to SCs were usually referred by a hospital
      provider (34%), followed by word of mouth (24%) and walk-in (22%). Seven of nine
      SCs were able to contribute data. Stability of SCs and capacity of staff emerged
      as facilitators of centralized data collection feasibility. CONCLUSION: We
      demonstrate that centralized data collection is feasible and that information to
      compare centers can be obtained. However, for more meaningful comparisons to
      emerge and to enable all SCs the ability to participate, support is needed
      institutionally for staff to be able to capture data and nationally to grow and
      sustain a database that represents the broader diversity of topics and services
      offered.

PMID- 26308117
TI  - Reporting on pediatric unintentional firearm injury--who's responsible.
AB  - BACKGROUND: Gun injury is a leading cause of death among US children and
      adolescents. Unintentional firearm death disproportionately affects youth.
      Reports have shown that at least a third of US homes with children have firearms.
      When children are fatally injured by guns, the location is most often a home, the
      shooter is family, the gun owner is a relative, and the gun most often originates
      from the home, where it was left unlocked. METHODS: We conducted an Internet
      search of pediatric (0-18 years old) fatal and nonfatal firearm injuries from
      January 1 to August 31, 2014, in the United States, querying the terms shot, gun,
      accident, and year-old for media reports. Cases were screened for intent and
      coded for demographics, location, gun specifics, circumstances, relationship
      between the victim, shooter, gun owner, and any resultant charges. RESULTS: A
      total of 277 unintentional pediatric gun injury events were reviewed, two-thirds
      were nonfatal. Half of the victims were younger than 13 years; 25.3% were younger
      than 7 years, 80% of the victims and 85.6% of the shooters were male. Of
      shooters, 84.3% were the child victim themselves, a family member, or a
      friend/acquaintance. Seventy-seven percent of the events took place in a
      residence. When gun ownership was reported, 68% were owned by a family member.
      When charges were reported, a third were against minors. CONCLUSION: This study
      reinforced previous studies that unintentional child firearm injuries
      predominantly involve the home, family guns, young children, and males, and most
      could be prevented through adult responsibility for minimizing child access and
      securing storage of firearms. We further learned that media accounts frequently
      did not report on gun ownership or charges, details which might increase
      community awareness or inform policies useful to prevention. Shooters, not
      owners, were more often charged in unintentional child injuries, and minors were
      charged even when Child Access Prevention laws could be applied. LEVEL OF
      EVIDENCE: Epidemiologic study, level 4.

PMID- 26308118
TI  - Impact of preseason concussion education on knowledge, attitudes, and behaviors
      of high school athletes.
AB  - BACKGROUND: The benefit of preseason concussion education on athletes' knowledge,
      attitudes, and behaviors is unclear. The purpose of the study was to determine
      the influence of preseason concussion education on knowledge and self-reported
      attitudes and reporting behaviors. We hypothesized that preseason education would
      lead to better knowledge and self-reported attitudes and better reporting of
      concussion symptoms during the season. METHODS: This study involved a prospective
      cohort comparing the benefits of a preseason lectured-based concussion education
      session at one high school with a control school. Participants included males and
      females age 13 years to 18 years from two community high schools who were
      participating in higher concussion risk, fall or winter sports (football, soccer,
      wrestling, and basketball). The education school and control school included 234
      and 262 participants, respectively. Outcomes were a preseason and postseason
      survey assessing knowledge and self-reported attitudes about concussions and an
      end-of-season questionnaire assessing concussion reporting behaviors during the
      season. RESULTS: Total scores on the combined (p < 0.0001), knowledge-based (p =
      0.016), and behavioral-based (p < 0.0001) questions demonstrated statistically
      significant improvement in the education group. Scores peaked immediately after
      education but dissipated at the end of the season. There was a lower proportion
      in the education school (72%) compared with the control school (88%) that
      reported continued play despite having concussion symptoms during the season (p =
      0.025). A similar proportion of athletes diagnosed with concussion during the
      season in the education (27%) and control schools (23%) reported returning to
      play before symptoms resolved (p = 0.81). CONCLUSION: These findings suggest that
      a didactic-based preseason concussion education likely has minimal benefits.
      Other factors besides knowledge are likely influencing student-athlete concussion
      reporting behavior. Future research focused on changing the culture of concussion
      reporting is needed. LEVEL OF EVIDENCE: Therapeutic study, level III.

PMID- 26308119
TI  - Permission to park: A statewide study of high school parking permits to determine
      compliance with graduated driver licensing law.
AB  - BACKGROUND: Motor vehicle crashes are the leading cause of fatality among teens
      in the United States. Beginning in the 1990s, many states enacted graduated
      driver licensing (GDL) systems to delay full licensure while allowing beginners
      to obtain experience under lower-risk conditions. Many high schools require
      parent and guardians of newly licensed teen drivers to complete a student parking
      pass application (PPA) for their son/daughter to drive, park, and transport
      themselves to and from school activities. The objective of this study was to
      describe the content of these PPAs for compliance with Connecticut's GDL law.
      METHODS: PPAs were requested via e-mail, fax, or telephone from all Connecticut's
      high schools (n = 233). PPA variables included school demographics, parking
      rules, prohibitions and sanctions for violations, as well as reference to GDL
      law. RESULTS: Seventy-four schools were excluded because students were not
      allowed to park and schools did not require PPAs or declined to send us a copy of
      their PPAs. Of the remaining 159 schools, 122 (76.7%) sent us their PPAs.
      Responding schools were more likely to be suburban or rural. Most PPAs included a
      section on prohibitions and sanctions for driving misbehavior. Forty-three
      percent prohibited students from going to car during school hours, and 34%
      prohibited driving off campus/parking lot. Seventy percent warned of consequences
      for dangerous driving in parking lot, and 88% included the possibility of
      revocation for infractions. Only 14% had any reference to Connecticut's GDL law
      on their PPAs. CONCLUSION: A small percentage of Connecticut high schools include
      information about GDL laws on their PPAs. All states should examine their PPA
      content and adopt a uniform high school PPA that includes key provisions of their
      state's GDL laws in an effort to promote teen driving safety. LEVEL OF EVIDENCE:
      Therapeutic study, level V.

PMID- 26308120
TI  - Graduated driver license compliant teens involved in fatal motor vehicle crashes.
AB  - BACKGROUND: Significant reductions in motor vehicle injury mortality have been
      reported for teen drivers after passage of graduated driver licensing (GDL), seat
      belt, and no tolerance alcohol and drug laws. Despite this, teen drivers remain a
      vulnerable population with elevated fatal crash involvement. This study examines
      driver, vehicle, and crash characteristics of GDL-compliant, belted, and
      unimpaired teen drivers with the goal of identifying areas where further
      improvements might be realized. METHODS: The Fatality Analysis Reporting System
      (FARS) for 2007 to 2009 was used to examine and classify driver violations/errors
      in compliant teen drivers (n = 1,571) of passenger vehicles involved in a fatal
      collision. Teens driving unbelted, non-GDL compliant, or impaired by alcohol or
      drugs were excluded. Statistical analysis used chi, Fisher's exact and
      multivariable logistic regression. Odds ratios are reported with 95% confidence
      intervals. Significance was defined as p < 0.05. RESULTS: Nearly one third (n =
      1,571) of teen drivers involved in a fatal motor vehicle crash were GDL
      compliant, unimpaired, and belted. The majority held an intermediate GDL license
      (90.6%). Crash-related factors were identified for 63.1% of fatal crashes. Age-
      and sex-adjusted odds identified overcorrecting, speeding, lane errors, school
      morning crashes, distractions, and driving on slippery surfaces as having
      increased odds of fatality for the teen driver as well as newer vehicle models
      and heavier vehicle weight as protective. CONCLUSION: Among compliant drivers,
      weekday crashes before and after school and committing a driving violation at the
      time of crash were associated with increased risk of driver death and higher
      incidence of incapacitating injury in surviving drivers. LEVEL OF EVIDENCE:
      Therapeutic study, level V.

PMID- 26308121
TI  - From focus groups to production of a distracted driving video: Using teen input
      to drive injury prevention programming.
AB  - BACKGROUND: The Impact program is an adolescent, injury prevention program with
      both school- and hospital-based components aimed at decreasing high-risk
      behaviors and preventing injury. The objective of this study was to obtain
      student input on the school-based component of Impact, as part of the program
      evaluation and redesign process, to ensure that the program content and format
      were optimal and relevant, addressing injury-related issues important for youth
      in our region. METHODS: Secondary schools were selected in various geographic
      regions with students varying in language, religion, and socioeconomic status. A
      mixed-methods questionnaire was developed and pretested on program content,
      format, relevance, quality, and effectiveness. Attitude and opinion questions on
      issues facing teens today were ranked on a 7-point Likert scale. Open-ended,
      qualitative questions were included in the focus groups, with responses themed.
      RESULTS: There were 167 respondents in the nine geographically,
      socioeconomically, and culturally diverse focus groups with a mean age of 16
      years, 52% were male, and 69% were in Grade 11. Ninety-three percent of
      respondents rated the content of Impact as comprehensive (median, 6 of 7, with 7
      being very comprehensive), and 29% rated the format a 5 of 7. Impact was rated
      relevant (89%), addressing issues for teens (median, 6 of 7). Issues suggested to
      highlight included texting and driving, drugs, partying, self-harm, and abusive
      relationships. Texting while driving was perceived as a significantly more common
      (81%) injury issue for adolescents compared with other driving risk factors (p <
      0.001), with one student commenting, "If you don't (text and drive), you either
      don't have a phone or don't have a driver's license." CONCLUSION: Injury
      prevention programs must be continually evaluated to ensure they are relevant,
      addressing issues important for youth, and presented in a format that resonates
      with the audience. Student focus groups identified motor vehicle collisions and
      texting as important issues as well as a desire for teens to hear personal
      stories with a visual element. This provided the information needed to develop
      the next logical direction for our program, the production of a distracted
      driving video ("Distracted Driving: Josh's Story," http://youtu.be/BFPke9gBybc)
      to be incorporated into school presentations. LEVEL OF EVIDENCE:
      Epidemiologic/prognostic study, level III.

PMID- 26308122
TI  - Car seat inspection among children older than 3 years: Using data to drive
      practice in child passenger safety.
AB  - BACKGROUND: Motor vehicle crashes are the leading cause of unintentional death
      and disability among children 4 years to 12 years of age in the United States.
      Despite the high risk of injury from motor vehicle crashes in this age group,
      parental awareness and child passenger safety programs in particular may lack
      focus on this age group. METHODS: This is a retrospective cross-sectional
      analysis of child passenger safety seat checklist forms from two Safe Kids
      coalitions in Michigan (2013) to identify restraint type upon arrival to car seat
      inspections. Other variables were included if the coalition provided a new child
      safety seat and if the child had a sibling who underwent a car seat inspection.
      chi statistics were used to compare change in restraint use on arrival and at
      departure, the proportion of children attending a car seat inspection event by
      age, the age category of children by site, the proportion of children with
      siblings also undergoing a car seat inspection by age, and the distribution of a
      new child safety seat by age. RESULTS: Data were available from 1,316 Safe Kids
      Huron Valley and 3,215 Safe Kids Greater Grand Rapids car seat inspections. Just
      10.8% of the total seats inspected were booster seats. Child safety seats for
      infant and young children were more commonly inspected (rear-facing carrier
      [40.3%], rear-facing convertible [10.2%], and forward-facing [19.3%] car seats).
      Few children at inspections used a seat belt only (5.4%) or had no restraint
      (13.8%). Children 4 years and older were found to be in a suboptimal restraint at
      least 30% of the time. CONCLUSION: Low proportions of parents use car seat
      inspections for children in the booster seat age group. The proportion of
      children departing the inspection in a more protective restraint increased with
      increasing age. This highlights an area of weakness in child passenger safety
      programs and signals an opportunity to strengthen efforts on The Booster Age
      Child. LEVEL OF EVIDENCE: Epidemiologic/prognostic study, level III.

PMID- 26308123
TI  - Restraint use in motor vehicle crash fatalities in children 0 year to 9 years
      old.
AB  - BACKGROUND: Despite improvements in child passenger safety legislation and
      equipment, motor vehicle crashes (MVCs) continue to be the leading cause of death
      in children younger than 10 years. The objective of this study was to describe
      factors associated with restraint use in fatal MVC in children 0 year to 9 years
      old. METHODS: The Fatality Analysis Reporting System, maintained by the National
      Highway Transportation Safety Administration, was used to obtain data on MVC
      fatalities from 2001 to 2010 in children 0 year to 9 years old. The main outcome
      was restraint use. Demographic information (age, sex, and race) and crash
      characteristics including vehicle type (sedan, van, truck, sports utility
      vehicle) and seat position in the vehicle were analyzed with the chi statistic to
      evaluate these factors for any restraint use compared with no restraint use in
      MVC fatalities. RESULTS: There were 7,625 MVC fatalities in children 0 year to 9
      years old from 2001 to 2010.Among these fatalities, 4,041 (53%) had any restraint
      use. Front seat passengers accounted for 20.9% (1,595 of 7,625) of the
      fatalities. Children 0 year to 3 years old had a higher proportion of restraint
      use than children 4 years to 9 years old (p < 0.001). White children compared
      with black children had higher use of restraints (p < 0.001). Children riding in
      sedans/vans compared with sport utility vehicles/trucks and those riding in the
      rear seats of the vehicle compared with those in front seats were significantly
      more likely to use restraints (p < 0.001). CONCLUSION: Overall, only half of
      children 0 year to 9 years old who died in an MVC were wearing any child
      restraint in the vehicle, and 20% were sitting in the front seat. Continued
      efforts must be made to enforce legislation and educate the public about best
      practices regarding child passenger safety to improve proper restraint use and to
      decrease MVC fatalities in children. LEVEL OF EVIDENCE: Prognostic/epidemiologic
      study, level II.

PMID- 26308125
TI  - Socially Accountable Medical Education-The REVOLUTIONS Framework.

PMID- 26308127
TI  - Prevalence of Arcobacter butzleri in the stool samples received in a tertiary
      hospital in Singapore: is it necessary to screen for it?

PMID- 26308126
TI  - A Study of the Use, Knowledge, and Beliefs About Cigarettes and Alternative
      Tobacco Products Among Students at One U.S. Medical School.
AB  - PURPOSE: In the United States, the prevalence of the use of alternative tobacco
      products (ATPs) (e.g., hookahs, e-cigarettes, cigars/cigarillos) has increased
      sharply. As future health care providers, medical students will play a critical
      role in health promotion and disease prevention. This study investigated medical
      students' use, knowledge, and beliefs about cigarettes and ATPs. METHOD: In 2014,
      the authors surveyed all students enrolled at one medical school in New York
      City. The survey included questions about personal use of tobacco products,
      perceptions about the harms of ATPs and their role in disease causation,
      education about ATPs, and cessation training and practices related to ATPs and
      cigarettes. The authors compared results across medical school classes. RESULTS:
      Of 720 students, 431 (59.9%) completed the survey. Of those, 64 (14.7%) were
      current users of tobacco or smoking products, including cigarettes (17; 3.9%),
      ATPs (21; 4.8%), or marijuana (39; 8.9%). Many believed that ATPs contributed
      less than cigarettes to various diseases. Respondents received less cessation
      training regarding ATPs than cigarettes (P < .0001). They felt less confident
      providing ATP cessation counseling than cigarette cessation counseling (P <
      .0001) and were less likely to report counseling patients on ATP cessation than
      cigarette cessation (46 [10.7%] versus 280 [64.8%], P < .0001). CONCLUSIONS: A
      concerning percentage of surveyed medical students use tobacco products,
      including ATPs, and lack the knowledge, education, and cessation counseling
      skills to provide accurate information about them to patients. ATP education
      should be added to medical school curricula to address this gap.

PMID- 26308128
TI  - Active surveillance for multidrug-resistant Gram-negative bacteria in the
      intensive care unit.
AB  - A short-term program of performing serial active screening cultures (ASC) in the
      intensive care unit was instituted to establish a method for the detection of
      antibiotic-resistant Gram-negative bacteria (GNB) and the local rates of
      colonisation. Of all submitted ASC, 25.9% (30/116 collected swabs) isolated an
      antibiotic-resistant GNB. ChromID ESBL agar (bioMerieux, France) identified the
      majority of these organisms, with the additional antibiotic-impregnated media
      [MacConkey agar (MCA) with ciprofloxacin, MCA with gentamicin and MCA with
      ceftazidime] adding limited benefit. Compared to swabs performed on admission,
      37.8% (14/37) of patients cultured a new antibiotic-resistant isolate on
      discharge. Serial screening in intensive care has the ability to identify
      patients with unrecognised colonisation with antibiotic-resistant GNB; however,
      the increase in the laboratory workload and logistical challenges in the
      collection of the surveillance swabs may limit this program's expansion. 

PMID- 26308129
TI  - Human case of Balantidium infection in Australia.

PMID- 26308131
TI  - Judicious application of controls as a cost-effective approach to routine
      diagnostic PCR testing.

PMID- 26308130
TI  - FOXP3+ T regulatory lymphocytes in primary melanoma are associated with BRAF
      mutation but not with response to BRAF inhibitor.
AB  - Tumour infiltrating lymphocytes in primary melanoma have been found to correlate
      with patient outcomes. A subpopulation of tumour infiltrating lymphocytes
      expresses the transcription factor forkhead box protein 3 (FOXP3). These are
      known as FOXP3+ T-regulatory cells (Tregs) and are thought to play an immune
      suppressive role in tumourigenesis. In most tumours, including melanoma, a high
      density of intratumoural FOXP3+ Tregs has been associated with poor prognosis. It
      is not known whether these cells also influence the response to BRAF inhibition
      therapy in metastatic melanoma. In the present study we retrospectively
      investigated the density of FOXP3+ Tregs in primary melanomas, with known
      subsequent metastasis, in relation to various clinicopathological parameters
      including BRAF and NRAS mutation status, and response to BRAF inhibitor therapy.
      The intratumoural density of FOXP3+ Tregs was two-fold higher in melanomas with
      mutant BRAF compared to those with wild type BRAF status (p = 0.03). In patients
      treated with BRAF kinase inhibitors FOXP3+ Treg density in the primary tumour was
      not predictive of treatment response (p = 0.38). 

PMID- 26308132
TI  - Evaluation of four chromogenic media for the isolation of Group B Streptococcus
      from vaginal specimens in pregnant women.
AB  - Direct culture onto four commercial chromogenic media, selective for the
      isolation of Group B Streptococcus (GBS), were compared with the conventional pre
      enrichment Centers for Disease Control and Prevention (CDC) method for the
      ability to isolate GBS from 242 pregnant women's self-collected vaginal/perineal
      swabs. The sensitivities and specificities for direct culture on to chromogenic
      agar were 92% and 100% for StrepBSelect (Bio-Rad Laboratories), 96% and 100% for
      Brilliance GBS (Thermo-Fisher Scientific), 94% and 100% for CHROMagar StrepB
      (CHROMagar, Dutec Diagnostics), 86% and 100% for ChromID Strepto B (bioMerieux).
      CDC recommended broth pre-enrichment then culture on blood containing selective
      agar had a sensitivity and specificity of 90.0% and 100% respectively. The
      chromogenic agar tested produced comparable results to the pre-enrichment CDC
      method. 

PMID- 26308133
TI  - Differential proteomic and tissue expression analyses identify valuable
      diagnostic biomarkers of hepatocellular differentiation and hepatoid
      adenocarcinomas.
AB  - The exact discrimination of lesions with true hepatocellular differentiation from
      secondary tumours and neoplasms with hepatocellular histomorphology like hepatoid
      adenocarcinomas (HAC) is crucial. Therefore, we aimed to identify ancillary
      protein biomarkers by using complementary proteomic techniques (2D-DIGE, label
      free MS). The identified candidates were immunohistochemically validated in 14
      paired samples of hepatocellular carcinoma (HCC) and non-tumourous liver tissue
      (NT). The candidates and HepPar1/Arginase1 were afterwards tested for consistency
      in a large cohort of hepatocellular lesions and NT (n = 290), non-hepatocellular
      malignancies (n = 383) and HAC (n = 13). Eight non-redundant, differentially
      expressed proteins were suitable for further immunohistochemical validation and
      four (ABAT, BHMT, FABP1, HAOX1) for further evaluation. Sensitivity and
      specificity rates for HCC/HAC were as follows: HepPar1 80.2%, 94.3% / 80.2%,
      46.2%; Arginase1 82%, 99.4% / 82%, 69.2%; BHMT 61.4%, 93.8% / 61.4%, 100%; ABAT
      84.4%, 33.7% / 84.4%, 30.8%; FABP1 87.2%, 95% / 87.2%, 69.2%; HAOX1 95.5%, 36.3%
      / 95.5%, 46.2%. The best 2*/3* biomarker panels for the diagnosis of HCC
      consisted of Arginase1/HAOX1 and BHMT/Arginase1/HAOX1 and for HAC consisted of
      Arginase1/FABP1 and BHMT/Arginase1/FABP1. In summary, we successfully identified,
      validated and benchmarked protein biomarker candidates of hepatocellular
      differentiation. BHMT in particular exhibited superior diagnostic characteristics
      in hepatocellular lesions and specifically in HAC. BHMT is therefore a promising
      (panel based) biomarker candidate in the differential diagnostic process of
      lesions with hepatocellular aspect. 

PMID- 26308134
TI  - Cutaneous ciliated cyst of the scrotum.

PMID- 26308135
TI  - Novel heterozygous Bbeta (c.1311T>A) mutation (Fibrinogen St Kilda) associated
      with recurrent pregnancy loss.

PMID- 26308136
TI  - Extensive bleeding due to an inhibitor in a haemophilia A patient with a
      Tyr2105Cys mutation: elimination of the inhibitor with rituximab.

PMID- 26308137
TI  - High grade neuroendocrine carcinoma of the urinary bladder treated by radical
      cystectomy: a series of small cell, mixed neuroendocrine and large cell
      neuroendocrine carcinoma.
AB  - High grade neuroendocrine carcinomas (HGNEC) treated by cystectomy often carry an
      original diagnosis of typical urothelial carcinoma (UC). The correct diagnosis of
      HGNEC is critical in influencing the decision for early chemotherapy, potentially
      followed by cystectomy. The objective of this study was to characterise the
      features of HGNEC treated by radical cystectomy. The study consisted of 79
      patients with HGNEC including small cell (68 patients), large cell neuroendocrine
      (LCNEC) (5 patients) and mixed neuroendocrine (mixed-NEC) carcinoma (6 patients)
      matched with 122 patients with UC, treated at our institution between 1987 and
      2014. Morphometric analysis for cell and nuclear size as well as
      immunophenotyping for neuroendocrine markers and cell-cycle regulators were
      applied to tissue microarrays. Small cell, LCNEC and mixed-NEC are a
      morphological spectrum of high grade neuroendocrine carcinoma with overlapping
      histological features, identical immunophenotype, Ki-67 proliferative rate and
      patient outcomes. Finally, the nuclear size criteria is misleading as HGNEC,
      particularly cases of LCNEC and mixed-NEC, may have enlarged nuclei compared to
      small cell carcinomas and are more prone to be misdiagnosed as UC, thereby
      preventing appropriate management. 

PMID- 26308138
TI  - Aggressive MLL gene rearranged CD7+ CD56+ myeloid / natural killer cell precursor
      acute leukaemia with extramedullary relapse in the uterus and breast.

PMID- 26308139
TI  - BRAFV600E mutation is rare in clear cell ovarian carcinoma, but could potentially
      be identified with mutation specific immunohistochemistry.

PMID- 26308141
TI  - [Management of Orbital Complications].
AB  - OBJECTIVE: Orbital complications of sinusitis represent serious diseases. In
      clinical practice, the term "orbital phlegmon" is often used, although this most
      serious expression of orbital infection is very rarely seen. However, a correct
      classification in each stage of orbital complications and resulting treatment
      recommendations are crucial for the prognosis of the patient. MATERIAL AND
      METHODS: Data from 49 patients who underwent treatment for orbital complications
      from 01/01/2000 until 31/12/2010 were retrospectively analysed. In particular,
      data on the epidemiology, diagnostic procedures and treatment methods were
      analyzed. RESULTS: From the observation period 109 patient records with the
      diagnosis "orbital affections" (ICD-10 H05) could be identified. Overall, data
      from 49 patients (36 male and 13 female) with orbital complications of sinusitis
      could be analyzed. 53.1% of the patient population were children and adolescents
      aged 1-20 years. Orbital complications were classified using the classification
      according to Chandler. The group I and II according to Chandler emerged most
      frequently. 26 patients (53.1%) showed a preseptal cellulitis (group I) and 11
      patients (22.4%) had an orbital cellulitis (group II). Patients from group III or
      higher according to Chandler received a combined medical and surgical treatment.
      CONCLUSIONS: Orbital complications of sinusitis mostly seem to arise in infancy
      and adolescence. With prompt identification of the orbital complications in stage
      I and II of Chandler, conservative therapy only could be successful. From the
      third stage up, sinus surgery needs to be considered. The classification of
      Chandler allows a correct recommendation of therapy.

PMID- 26308142
TI  - Diastereoselective Fluorocyclopropanation of Chiral Allylic Alcohols Using an
      alpha-Fluoroiodomethylzinc Carbenoid.
AB  - Chiral fluorocyclopropyl carbinols were synthesized in high
      diastereoselectivities via a zinc mediated cyclopropanation reaction, using sec
      allylic alcohols as simple building blocks. An enantioselective version of this
      transformation was achieved through in situ formation of chiral allylic zinc sec
      alkoxides from the requisite aldehydes using Walsh's protocol. 

PMID- 26308143
TI  - Bioanalytical and chemical sensors using living taste, olfactory, and neural
      cells and tissues: a short review.
AB  - Biosensors utilizing living tissues and cells have recently gained significant
      attention as functional devices for chemical sensing and biochemical analysis.
      These devices integrate biological components (i.e. single cells, cell networks,
      tissues) with micro-electro-mechanical systems (MEMS)-based sensors and
      transducers. Various types of cells and tissues derived from natural and
      bioengineered sources have been used as recognition and sensing elements, which
      are generally characterized by high sensitivity and specificity. This review
      summarizes the state of the art in tissue- and cell-based biosensing platforms
      with an emphasis on those using taste, olfactory, and neural cells and tissues.
      Many of these devices employ unique integration strategies and sensing schemes
      based on sensitive transducers including microelectrode arrays (MEAs), field
      effect transistors (FETs), and light-addressable potentiometric sensors (LAPSs).
      Several groups have coupled these hybrid biosensors with microfluidics which
      offers added benefits of small sample volumes and enhanced automation. While this
      technology is currently limited to lab settings due to the limited stability of
      living biological components, further research to enhance their robustness will
      enable these devices to be employed in field and clinical settings. 

PMID- 26308144
TI  - Bioorthogonal phase-directed copper-catalyzed azide-alkyne cycloaddition
      (PDCuAAC) coupling of selectively cross-linked superoxide dismutase dimers
      produces a fully active bis-dimer.
AB  - Superoxide dismutase (SOD) is a 32 kDa dimeric enzyme that actively removes a
      toxic oxygen species within red cells. The acellular protein itself does not
      survive circulation as it is filtered through the kidney. Conjugating the protein
      to another SOD should increase the size of the dual protein above the threshold
      for filtration by the kidney, making the material a potential therapeutic in
      circulation. Site-selective chemical cross-linking of SOD introduces a
      bioorthogonal azide group on the cross-link so that two SODs react efficiently
      with a bis-alkyne through phase-directed copper-catalyzed azide-alkyne
      cycloaddition (PDCuAAC). The modification has a negligible effect on the
      catalytic activity of the constituent proteins. Consistent with the retained
      activity, circular dichroism (CD) spectroscopy indicates that the secondary
      structures of the proteins are similar to that of the native protein. 

PMID- 26308145
TI  - Inclusion complexation between baicalein and beta-cyclodextrin and the influence
      of beta-cyclodextrin on the binding of baicalein with DNA: a spectroscopic
      approach.
AB  - This work deals with the commonly studied cyclic oligosaccharide and gains
      importance as it is entered on a drug delivering carbohydrate and provides
      insight into the oligosaccharide complex-biomolecular interaction. The binding of
      a flavone, baicalein, to beta-cyclodextrin and calf thymus DNA is studied. The
      binding of baicalein to calf thymus DNA in the presence of beta-cyclodextrin is
      analysed using the UV-vis absorption and fluorescence spectroscopy. The mode of
      binding and structure of the baicalein-beta-cyclodextrin complex are reported.
      The role of the structure and the stoichiometry of the inclusion complex of
      baicalein-beta-cyclodextrin in its influence on DNA binding are analysed.
      Highlights * This paper deals with the binding of a flavone, baicalein to beta
      cyclodextrin and/or DNA. * The inclusion complexation between baicalein and beta
      cyclodextrin is analysed. * The stoichiometry and the binding strength of the
      inclusion complex is reported. * The role of beta-cyclodextrin in tuning the
      binding of baicalein to DNA is emphasized. * Spectroscopic and docking analysis
      are used to articulate the results. 

PMID- 26308146
TI  - Stable, highly-responsive and broadband photodetection based on large-area
      multilayered WS2 films grown by pulsed-laser deposition.
AB  - The progress in the field of graphene has aroused a renaissance of keen research
      interest in layered transition metal dichalcogenides (TMDs). Tungsten disulfide
      (WS2), a typical TMD with favorable semiconducting band gap and strong light
      matter interaction, exhibits great potential for highly-responsive
      photodetection. However, WS2-based photodetection is currently unsatisfactory due
      to the low optical absorption (2%-10%) and poor carrier mobility (0.01-0.91 cm(2)
      V(-1) s(-1)) of the thin WS2 layers grown by chemical vapor deposition (CVD).
      Here, we introduce pulsed-laser deposition (PLD) to prepare multilayered WS2
      films. Large-area WS2 films of the magnitude of cm(2) are achieved. Comparative
      measurements of a WS2-based photoresistor demonstrate its stable broadband
      photoresponse from 370 to 1064 nm, the broadest range demonstrated in WS2
      photodetectors. Benefiting from the large optical absorbance (40%-85%) and high
      carrier mobility (31 cm(2) V(-1) s(-1)), the responsivity of the device
      approaches a high value of 0.51 A W(-1) in an ambient environment. Such a
      performance far surpasses the CVD-grown WS2-based photodetectors (MUA W(-1)). In
      a vacuum environment, the responsivity is further enhanced to 0.70 A W(-1) along
      with an external quantum efficiency of 137% and a photodetectivity of 2.7 * 10(9)
      cm Hz(1/2) W(-1). These findings stress that the PLD-grown WS2 film may
      constitute a new paradigm for the next-generation stable, broadband and highly
      responsive photodetectors. 

PMID- 26308147
TI  - Effect of Age on Psychiatric Rehospitalization Rates After Electroconvulsive
      Therapy for Patients With Depression.
AB  - OBJECTIVES: The aims of this naturalistic study are to examine psychiatric
      rehospitalization rates in geriatric compared to nongeriatric patients who
      receive electroconvulsive therapy (ECT) and to characterize the sustained
      effectiveness of ECT for treatment of depression. METHODS: Retrospective review
      of electronic medical records at a tertiary care center for patients with major
      depressive disorder who received an acute course of ECT at an index psychiatric
      hospitalization over a 5-year period. Data for subsequent psychiatric and primary
      care encounters were ascertained by chart review. Outcomes of interest included
      between-group differences in rates of psychiatric rehospitalization, time to
      rehospitalization, rates of other types of clinical follow-up care, and effect of
      demographic variables on clinical outcome. RESULTS: Of 482 total patients, there
      were 210 (44%) geriatric patients (>=65 years). These patients experienced lower
      overall rates of psychiatric rehospitalization after ECT (6.2% vs 22%; P <
      0.0001) compared to the nongeriatric group. Cox proportional hazard models
      indicated that older age, assessed both as a dichotomous and continuous variable,
      was associated with lower risk of rehospitalization. The majority (76.9%) of
      detected rehospitalizations among geriatric patients occurred within 6 months. In
      comparison, rates of outpatient primary care and psychiatric follow-up after ECT
      did not differ as a function of age. CONCLUSIONS: Our findings suggest that
      geriatric patients with major depression receive greater long-term benefit from
      an acute course of ECT than do nongeriatric patients. Much more research is
      needed on this topic to rigorously evaluate the long-term efficacy of ECT in
      geriatric populations.

PMID- 26308149
TI  - Reactivity of platinum alkyne complexes towards N-fluorobenzenesulfonimide:
      formation of platinum compounds bearing a beta-fluorovinyl ligand.
AB  - The platinum(0) alkyne complexes [Pt(L)(eta(2)-PhC[triple bond, length as m
      dash]CPh)] 1-4 were synthesized by reactions of [Pt(cod)2] with diphenylacetylene
      and a phosphine ligand precursor (1: L = dcpe, 2: L = xantphos, 3: L = kappa(2)
      (P,N)-iPr2PC3H6NMe2, 4: L = kappa(2)-(P,N)-iPr2PC2H4NMe2). Treatment of 1 or 4
      with NFSI gave the complexes [Pt(F){N(SO2Ph)2}(dcpe)] (5) and [Pt(PhC[double
      bond, length as m-dash]CFPh){N(SO2Ph)2}{kappa(2)-(P,N)-iPr2PC2H4NMe2}] (8),
      whereas the reactivity of 2 and 3 towards NFSI led to product mixtures. The
      compounds [Pt(F){N(SO2Ph)2}(xantphos)] (6a) as well as [Pt(PhC[double bond,
      length as m-dash]CFPh){N(SO2Ph)2}{kappa(2)-(P,N)-iPr2PC2H4NMe2}] (7a) and
      [Pt(PhC[double bond, length as m-dash]CFPh)(F){kappa(2)-(P,N)-iPr2PC2H4NMe2}]
      (7b) were clearly identified. Ligand exchange reactions at 8 resulted in the
      formation of the beta-fluorovinyl platinum(ii) complexes [Pt(PhC[double bond,
      length as m-dash]CFPh){OC(O)CF3}{kappa(2)-(P,N)-iPr2PC2H4NMe2}] (9),
      [Pt(PhC[double bond, length as m-dash]CFPh)(FHF){kappa(2)-(P,N)-iPr2PC2H4NMe2}]
      (10) and [Pt(PhC[double bond, length as m-dash]CFPh)(F){kappa(2)-(P,N)
      iPr2PC2H4NMe2}] (11). Treatment of 8 with dihydrogen yielded the fluorinated
      olefin (Z)-(1-fluoroethene-1,2-diyl)dibenzene and [Pt{N(SO2Ph)2}(H){kappa(2)
      (P,N)-iPr2PC2H4NMe2}] (12). 

PMID- 26308150
TI  - Evaluating environmental DNA-based quantification of ranavirus infection in wood
      frog populations.
AB  - A variety of challenges arise when monitoring wildlife populations for disease.
      Sampling tissues can be invasive to hosts, and obtaining sufficient sample sizes
      can be expensive and time-consuming, particularly for rare species and when
      pathogen prevalence is low. Environmental DNA (eDNA)-based detection of pathogens
      is an alternative approach to surveillance for aquatic communities that
      circumvents many of these issues. Ranaviruses are emerging pathogens of
      ectothermic vertebrates linked to die-offs of amphibian populations. Detecting
      ranavirus infections is critical, but nonlethal methods have the above issues and
      are prone to false negatives. We report on the feasibility and effectiveness of
      eDNA-based ranavirus detection in the field. We compared ranavirus titres in eDNA
      samples collected from pond water to titres in wood frog (Lithobates sylvaticus;
      n = 5) tadpoles in sites dominated by this one species (n = 20 pond visits). We
      examined whether ranavirus DNA can be detected in eDNA from pond water when
      infections are present in the pond and if viral titres detected in eDNA samples
      correlate with the prevalence or intensity of ranavirus infections in tadpoles.
      With three 250 mL water samples, we were able to detect the virus in all visits
      with infected larvae (0.92 diagnostic sensitivity). Also, we found a strong
      relationship between the viral eDNA titres and titres in larval tissues. eDNA
      titres increased prior to observed die-offs and declined afterwards, and were two
      orders of magnitude higher in ponds with a die-off. Our results suggest that eDNA
      is useful for detecting ranavirus infections in wildlife and aquaculture.

PMID- 26308151
TI  - Reliability of the Dutch translation of the Kujala Patellofemoral Score
      Questionnaire.
AB  - OBJECTIVE: There are no Dutch language disease-specific questionnaires for
      patients with patellofemoral pain syndrome available that could help Dutch
      physiotherapists to assess and monitor these symptoms and functional limitations.
      The aim of this study was to translate the original disease-specific Kujala
      Patellofemoral Score into Dutch and evaluate its reliability. METHODS: The
      questionnaire was translated from English into Dutch in accordance with
      internationally recommended guidelines. Reliability was determined in 50 stable
      subjects with an interval of 1 week. The patient inclusion criteria were age
      between 14 and 60 years; knowledge of the Dutch language; and the presence of at
      least three of the following symptoms: pain while taking the stairs, pain when
      squatting, pain when running, pain when cycling, pain when sitting with knees
      flexed for a prolonged period, grinding of the patella and a positive clinical
      patella test. The internal consistency, test-retest reliability, measurement
      error and limits of agreement were calculated. RESULTS: Internal consistency was
      0.78 for the first assessment and 0.80 for the second assessment. The intraclass
      correlation coefficient (ICCagreement ) between the first and second assessments
      was 0.98. The mean difference between the first and second measurements was 0.64,
      and standard deviation was 5.51. The standard error measurement was 3.9, and the
      smallest detectable change was 11. The Bland and Altman plot shows that the
      limits of agreement are -10.37 and 11.65. CONCLUSIONS: The results of the present
      study indicated that the test-retest reliability translated Dutch version of the
      Kujala Patellofemoral Score questionnaire is equivalent of the test-retest
      original English language version and has good internal consistency. Trial
      registration NTR (TC = 3258). Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 26308152
TI  - Genetic analysis of SLC41A1 in Chinese Parkinson's disease patients.
AB  - Sequence variants in SLC41A1 (solute carrier family 41 member 1) within the
      PARK16 locus have been reported to be associated with Parkinson's disease (PD).
      We performed direct DNA sequencing of the SLC41A1 gene in 100 early-onset PD
      cases. A novel intron variant (NM_173854.5:c.993-90delA) and a known synonymous
      coding variant (NM_173854.5:c.339 C>T, causing p.Thr113Thr, rs11240569) were
      identified in the SLC41A1 gene. Then we genotyped the rs11240569 variant in a
      total of 2237 Han Chinese comprising of 1063 sporadic PD and 1174 controls to
      investigate the association with risk of PD, we also conducted further stratified
      analysis according to age at onset and compared the clinical characteristics of
      CC + CT subjects with TT subjects. In this study, we confirmed that the C allele
      of SLC41A1 (rs11240569) polymorphism reduces the risk to develop sporadic PD (P =
      0.018). Additionally, subjects with CC + CT genotypes have a reduced risk
      compared to those with TT genotype (P = 0.022), the association was modestly seen
      among the younger age group (P = 0.05), but was not significant among the older
      age group (P = 0.641). Besides, we demonstrated that CC + CT subjects cannot be
      distinguished from TT subjects based on their clinical features. Our study, the
      first demonstrates that SLC41A1 (rs11240569) is associated with a lower risk of
      PD in a Han Chinese population from mainland China.

PMID- 26308153
TI  - Onabotulinum toxin A dosage trends over time for adductor spasmodic dysphonia: A
      15-year experience.
AB  - OBJECTIVES/HYPOTHESIS: Although onabotulinum neurotoxin A (BoNTA) has been used
      for over three decades for the treatment of adductor spasmodic dysphonia, no
      study has been performed to look at the trend of BoNTA dosages across time. The
      goal of this study is to evaluate the dosage trends to determine if the dosage
      necessary for voice improvement in patients increases over time. STUDY DESIGN:
      Charts were reviewed for patients with 15 years or more of experience. METHODS:
      Linear regression analysis was performed to determine correlation coefficients
      and trends. RESULTS: Fifty-five patients receiving BoNTA injections by the senior
      author (a.b.) for over 15 years were evaluated. Thirty-nine patients (82% female)
      met inclusion criteria. Patients received injections over an average of 18.6
      years +/- 1.36 years, with the longest follow-up of 21.5 years. Of 39 patients,
      16 (41%) had a negative correlation coefficient (Pearson's r) suggesting a
      decrease over time, whereas 23 (59%) had a positive correlation coefficient
      suggesting an increase over time. The mean correlation coefficient was 0.139 +/-
      0.534 and P < 0.05 in 19 patients and P > 0.05 in 20 patients. R(2) for all
      patients were less than 0.75. CONCLUSIONS: Onabotulinum neurotoxin A injection
      dosage trends vary depending on the individual over time. Overall, the dose range
      appears to be stable in the majority of patients, suggesting that tolerance does
      not play a significant part in dose variation over time. LEVEL OF EVIDENCE: 4.
      Laryngoscope, 126:678-681, 2016.

PMID- 26308154
TI  - Genetic diversity and distribution patterns of diploid and polyploid hybrid water
      frog populations (Pelophylax esculentus complex) across Europe.
AB  - Polyploidization is a rare yet sometimes successful way for animals to rapidly
      create geno- and phenotypes that may colonize new habitats and quickly adapt to
      environmental changes. In this study, we use water frogs of the Pelophylax
      esculentus complex, comprising two species (Pelophylax lessonae, genotype LL;
      Pelophylax ridibundus, RR) and various diploid (LR) and triploid (LLR, LRR)
      hybrid forms, summarized as P. esculentus, as a model for studying recent
      hybridization and polyploidization in the context of speciation. Specifically, we
      compared the geographic distribution and genetic diversity of diploid and
      triploid hybrids across Europe to understand their origin, maintenance and
      potential role in hybrid speciation. We found that different hybrid and parental
      genotypes are not evenly distributed across Europe. Rather, their genetic
      diversity is structured by latitude and longitude and the presence/absence of
      parental species but not of triploids. Highest genetic diversity was observed in
      central and eastern Europe, the lowest in the northwestern parts of Europe. This
      gradient can be explained by the decrease in genetic diversity during postglacial
      expansion from southeastern glacial refuge areas. Genealogical relationships
      calculated on the basis of microsatellite data clearly indicate that hybrids are
      of multiple origin and include a huge variety of parental genomes. Water frogs in
      mixed-ploidy populations without any parental species (i.e. all-hybrid
      populations) can be viewed as evolutionary units that may be on their way towards
      hybrid speciation. Maintenance of such all-hybrid populations requires a
      continuous exchange of genomes between diploids and triploids, but scenarios for
      alternative evolutionary trajectories are discussed. 

PMID- 26308155
TI  - Does fat suppression via chemically selective saturation affect R2*-MRI for
      transfusional iron overload assessment? A clinical evaluation at 1.5T and 3T.
AB  - PURPOSE: Fat suppression (FS) via chemically selective saturation (CHESS)
      eliminates fat-water oscillations in multiecho gradient echo (mGRE) R2*-MRI.
      However, for increasing R2* values as seen with increasing liver iron content
      (LIC), the water signal spectrally overlaps with the CHESS band, which may alter
      R2*. We investigated the effect of CHESS on R2* and developed a heuristic
      correction for the observed CHESS-induced R2* changes. METHODS: Eighty patients
      [female, n = 49; male, n = 31; mean age (+/- standard deviation), 18.3 +/- 11.7
      y] with iron overload were scanned with a non-FS and a CHESS-FS mGRE sequence at
      1.5T and 3T. Mean liver R2* values were evaluated using three published fitting
      approaches. Measured and model-corrected R2* values were compared and
      statistically analyzed. RESULTS: At 1.5T, CHESS led to a systematic R2* reduction
      (P < 0.001 for all fitting algorithms) especially toward higher R2*. Our model
      described the observed changes well and reduced the CHESS-induced R2* bias after
      correction (linear regression slopes: 1.032/0.927/0.981). No CHESS-induced R2*
      reductions were found at 3T. CONCLUSION: The CHESS-induced R2* bias at 1.5T needs
      to be considered when applying R2*-LIC biopsy calibrations for clinical LIC
      assessment, which were established without FS at 1.5T. The proposed model
      corrects the R2* bias and could therefore improve clinical iron overload
      assessment based on linear R2*-LIC calibrations. Magn Reson Med 76:591-601, 2016.
      (c) 2015 Wiley Periodicals, Inc.

PMID- 26308156
TI  - The role of aldo-keto reductase 1C3 (AKR1C3)-mediated prostaglandin D2 (PGD2)
      metabolism in keloids.
AB  - Keloids are progressively expanding scars, mostly prevalent in individuals of
      African descent. Previous data identified increased mast cell number and
      activation state in keloids suggesting a role in disease progression. The major
      eicosanoid secreted by mast cells is prostaglandin D2 (PGD2), a relatively
      unstable pro-inflammatory mediator which can be spontaneously converted to 15
      deoxy-(Delta12,14)-prostaglandin J2(15d-PGJ2) or enzymatically metabolized to
      9alpha,11beta-PGF2 by aldo-keto reductase 1C3 (AKR1C3). In this work, we
      investigated the possible role of PGD2 and its metabolites in keloids using
      CRL1762 keloid fibroblasts (KF) and immunohistochemical staining. Our data
      suggested approximately 3-fold increase of tryptase-positive mast cell count in
      keloids compared with normal skin. Furthermore, AKR1C3 was overexpressed in the
      fibrotic area of keloids while relatively weak staining detected in normal skin.
      Metabolism of PGD2 to 9alpha,11beta-PGF2 by both, KF and normal fibroblasts, was
      dependent on AKR1C3 as this reaction was attenuated in the presence of the AKR1C3
      inhibitor, 2'-hydroxyflavanone, or in cells with decreased AKR1C3 expression. 15d
      PGJ2, but not the other tested PGs, inhibited KF proliferation, attenuated KF
      mediated collagen gel contraction and increased caspase-3 activation. In
      addition, treatment with 15d-PGJ2 activated P38-MAPK, induced reactive oxygen
      species and upregulated superoxide dismutase-1 (SOD-1). Finally, inhibition of
      P38-MAPK further augmented 15d-PGJ2-induced caspase-3 cleavage and attenuated its
      effect on SOD-1 transcription. This work suggests that localized dual inhibition
      of AKR1C3 and P38-MAPK may inhibit keloid progression. Inhibiting AKR1C3 activity
      may generate oxidative environment due to redirection of PGD2 metabolism towards
      15d-PGJ2 while inhibition of P38-MAPK will sensitize keloid cells to ROS-induced
      apoptosis. 

PMID- 26308157
TI  - Objectively measured physical activity and sedentary behavior and quality of life
      indicators in survivors of breast cancer.
AB  - BACKGROUND: The primary purpose of the current study was to determine prospective
      associations of accelerometer-assessed physical activity intensity and sedentary
      time with health-related quality of life (HRQOL) indicators among survivors of
      breast cancer. METHODS: A total of 358 survivors of breast cancer wore an
      accelerometer for 7 days at baseline to assess different activity intensities
      (light, lifestyle, and moderate to vigorous) and sedentary behavior. Six months
      later, survivors completed online questionnaires that assessed HRQOL indicators
      (disease-specific HRQOL, fatigue, depression, and anxiety) and relevant
      covariates. Relationships between activity and sedentary behavior quartiles and
      HRQOL indicator scores were examined using generalized liner models with
      Bonferroni multiple comparison adjustment. RESULTS: After adjustment for
      covariates and sedentary time, each increasing lifestyle activity quartile was
      associated with reduced fatigue duration (P for trend, .03). Each increasing
      baseline moderate-to-vigorous physical activity (MVPA) quartile was found to be
      significantly associated with higher Physical Well-Being, Functional Assessment
      of Cancer Therapy-Breast (FACT-B) total, and trial outcome index scores; fewer
      breast cancer-specific concerns; and lower fatigue interference, and these
      differences were statistically and clinically significant between survivors in
      quartile 1 and quartile 4. After controlling for covariates and MVPA,
      relationships between sedentary time and HRQOL were mostly null with the
      exception of lower fatigue duration. CONCLUSIONS: Objectively measured MVPA was
      found to be positively associated with many HRQOL indicators. Lifestyle activity
      was found to be only inversely associated with fatigue duration whereas sedentary
      time was found to be positively associated with fatigue duration. Future research
      is warranted to explore these relationships further.

PMID- 26308158
TI  - Aging Versus Postmenopausal Osteoporosis: Bone Composition and Maturation
      Kinetics at Actively-Forming Trabecular Surfaces of Female Subjects Aged 1 to 84
      Years.
AB  - Bone strength depends on the amount of bone, typically expressed as bone mineral
      density (BMD), determined by dual-energy X-ray absorptiometry (DXA), and on bone
      quality. Bone quality is a multifactorial entity including bone structural and
      material compositional properties. The purpose of the present study was to
      examine whether bone material composition properties at actively-forming
      trabecular bone surfaces in health are dependent on subject age, and to contrast
      them with postmenopausal osteoporosis patients. To achieve this, we analyzed by
      Raman microspectroscopy iliac crest biopsy samples from healthy subjects aged 1.5
      to 45.7 years, paired biopsy samples from females before and immediately after
      menopause aged 46.7 to 53.6 years, and biopsy samples from placebo-treated
      postmenopausal osteoporotic patients aged 66 to 84 years. The monitored
      parameters were as follows: the mineral/matrix ratio; the mineral
      maturity/crystallinity (MMC); nanoporosity; the glycosaminoglycan (GAG) content;
      the lipid content; and the pyridinoline (Pyd) content. The results indicate that
      these bone quality parameters in healthy, actively-forming trabecular bone
      surfaces are dependent on subject age at constant tissue age, suggesting that
      with advancing age the kinetics of maturation (either accumulation, or
      posttranslational modifications, or both) change. For most parameters, the
      extrapolation of models fitted to the individual age dependence of bone in
      healthy individuals was in rough agreement with their values in postmenopausal
      osteoporotic patients, except for MMC, lipid, and Pyd content. Among these three,
      Pyd content showed the greatest deviation between healthy aging and disease,
      highlighting its potential to be used as a discriminating factor.

PMID- 26308159
TI  - Molecular characterization of adenoviruses among finnish military conscripts.
AB  - Although adenoviruses were identified as important respiratory pathogens many
      years ago, little information is available concerning the prevalence of different
      adenovirus serotypes, which are circulating and causing epidemics in Finnish
      military training centers. Over a period of five years from 2008 to 2012, 3577
      respiratory specimens were collected from military conscripts presenting with
      symptoms compatible with acute respiratory tract infection. Upon initial testing
      for certain respiratory viruses by real-time PCR, 837 of these specimens were
      identified as adenovirus-positive. For 672 of these specimens, the serotype of
      the adenovirus responsible was successfully determined by DNA sequencing.
      Serotypes 1, 2, 3, and 4 were detected in 1, 3, 181, and 487 samples,
      respectively. Adenovirus epidemics were observed during each year of this study.
      Based on these findings, adenovirus vaccination should be considered for military
      conscripts in the Finnish Defence Forces.

PMID- 26308161
TI  - Emodin ameliorates lipopolysaccharides-induced corneal inflammation in rats.
AB  - AIM: To investigate the effect of emodin on pseudomonas aeruginosa
      lipopolysaccharides (LPS)-induced corneal inflammation in rats. METHODS: Corneal
      infection was induced by pseudomonas aeruginosa LPS in Wistar rats. The
      inflammation induced by LPS were examined by slit lamp microscope and cytological
      checkup of aqueous humor. Corneal tissue structure was observed by hematoxylin
      and eosin (HE) staining. The activation of nuclear factor kappaB (NF-kappaB) was
      determined by Western blot. Messenger ribonucleic acid (mRNA) of tumor necrosis
      factor-alpha (TNF-alpha) and intercellular adhesion molecule-1 (ICAM-1) in LPS
      challenged rat corneas were measured with reverse transcription-polymerase chain
      reaction (RT-PCR). RESULTS: Typical manifestations of acute corneal inflammation
      were observed in LPS-induce rat model, and the corneal inflammatory response and
      structure were improved in rats pretreated with emodin. Treatment with emodin
      could improve corneal structure, reduce corneal injure by reducing corneal
      inflammatory response. Emodin could inhibit the decreasing lever of inhibitor of
      kappaB alpha (IkBalpha) express, and the mRNA expression of TNF-alpha and ICAM-1
      in corneal tissues was also inhibited by emodin. The differences were
      statistically significant between groups treated with emodin and those without
      treatment (P<0.01). CONCLUSION: Emodin could ameliorate LPS-induced corneal
      inflammation, which might via inhibiting the activation of NF-kappaB.

PMID- 26308163
TI  - Morbidity and Mortality Associated With Elective or Emergency Paraesophageal
      Hernia Repair.

PMID- 26308165
TI  - Spatial mapping of fluorophore quantum yield in diffusive media.
AB  - Fluorescence quantum yield (QY) indicates the efficiency of the fluorescence
      process. The QY of many fluorophores is sensitive to local tissue environments,
      highlighting the possibility of using QY as an indicator of important parameters
      such as pH or temperature. QY is commonly measured by comparison to a well-known
      standard in nonscattering media. We propose a new imaging method, called quantum
      yield imaging (QYI), to spatially map the QY of a fluorophore within an optically
      diffusive media. QYI utilizes the wide-field diffuse optical technique spatial
      frequency domain imaging (SFDI) as well as planar fluorescence imaging. SFDI is
      used to measure the optical properties of the background media and the absorption
      contributed by the fluorophore. The unknown QY is then calculated by combining
      information from both modalities. A fluorescent sample with known QY is used to
      account for instrument response. To demonstrate QYI, rhodamine B and SNARF-5 were
      imaged in liquid phantoms with different background optical properties. The
      methanol:water ratio and pH were changed for rhodamine B and SNARF-5 solvents,
      respectively, altering the QY of each through a wide range. QY was determined
      with an agreement of 0.021 and 0.012 for rhodamine B and SNARF-5, respectively.

PMID- 26308164
TI  - Quantifying hyperoxia-mediated damage to mammalian respiratory cilia-driven fluid
      flow using particle tracking velocimetry optical coherence tomography.
AB  - Oxygen supplementation [hyperoxia, increased fraction of inspired oxygen (FiO 2
      )] is an indispensable treatment in the intensive care unit for patients in
      respiratory failure. Like other treatments or drugs, hyperoxia has a risk-benefit
      profile that guides its clinical use. While hyperoxia is known to damage
      respiratory epithelium, it is unknown if damage can result in impaired capacity
      to generate cilia-driven fluid flow. Here, we demonstrate that quantifying cilia
      driven fluid flow velocities in the sub-100 MUm/s regime (sub-0.25 in./min
      regime) reveals hyperoxia-mediated damage to the capacity of ciliated respiratory
      mucosa to generate directional flow. Flow quantification was performed using
      particle tracking velocimetry optical coherence tomography (PTV-OCT) in ex vivo
      mouse trachea. The ability of PTV-OCT to detect biomedically relevant flow
      perturbations in the sub-100 MUm/s regime was validated by quantifying
      temperature- and drug-mediated modulation of flow performance in ex vivo mouse
      trachea. Overall, PTV-OCT imaging of cilia-driven fluid flow in ex vivo mouse
      trachea is a powerful and straightforward approach for studying factors that
      modulate and damage mammalian respiratory ciliary physiology.

PMID- 26308162
TI  - A decade of EGFR inhibition in EGFR-mutated non small cell lung cancer (NSCLC):
      Old successes and future perspectives.
AB  - The discovery of Epidermal Growth Factor Receptor (EGFR) mutations in Non Small
      Cell Lung Cancer (NSCLC) launched the era of personalized medicine in advanced
      NSCLC, leading to a dramatic shift in the therapeutic landscape of this disease.
      After ten years from the individuation of activating mutations in the tyrosine
      kinase domain of the EGFR in NSCLC patients responding to the EGFR tyrosine
      kinase inhibitor (TKI) Gefitinib, several progresses have been done and first
      line treatment with EGFR TKIs is a firmly established option in advanced EGFR
      mutated NSCLC patients. During the last decade, different EGFR TKIs have been
      developed and three inhibitors have been approved so far in these selected
      patients. However, despite great breakthroughs have been made, treatment of these
      molecularly selected patients poses novel therapeutic challenges, such as
      emerging of acquired resistance, brain metastases development or the need to
      translate these treatments in earlier clinical settings, such as adjuvant
      therapy. The aim of this paper is to provide a comprehensive review of the major
      progresses reported so far in the EGFR inhibition in this molecularly-selected
      subgroup of NSCLC patients, from the early successes with first generation EGFR
      TKIs, Erlotinib and Gefitinib, to the novel irreversible and mutant-selective
      inhibitors and ultimately the emerging challenges that we, in the next future,
      are called to deal with. 

PMID- 26308166
TI  - Site-specific characterization and absolute quantification of pegfilgrastim
      oxidation by top-down high-performance liquid chromatography-mass spectrometry.
AB  - The characterization and absolute quantification of protein biopharmaceuticals
      and their product-related impurities, e.g., oxidation variants, is essential due
      to their potential impact on biological activity and immunogenicity. Here, we
      present site assignment and absolute quantification of oxidation variants of
      pegfilgrastim, a poly(ethylene glycol) modified recombinant human granulocyte
      colony stimulating factor. Pegfilgrastim stressed with 1.0% hydrogen peroxide
      served as a model protein for developing a top-down high-performance liquid
      chromatography-mass spectrometry (HPLC-MS) platform that allowed direct site
      assignment of Met122, Met127, and Met138 oxidation within a total analysis time
      of 30 min. Three different absolute quantification methods, namely, UV absorption
      spectroscopy, full-scan MS, and all-ion fragmentation (AIF) MS were compared.
      Additionally, the monitoring of all generated fragment ions or selected sets of
      fragment ions were evaluated for the AIF method. Linearity of calibration curves
      from 5.0 to 25 ng MUL(-1), 25 to 250 ng MUL(-1), and 100 to 1000 ng MUL(-1) was
      confirmed. The AIF method achieved a lower limit of detection of 0.85 ng MUL(-1)
      and a lower limit of quantification of 2.54 ng MUL(-1). On the basis of the
      comparison of relative standard deviations of interday measurements, AIF was
      concluded to be the method of choice for concentrations up to 50 ng MUL(-1), and
      UV measurements should be carried out above this concentration. Finally, an
      expired pegfilgrastim batch was analyzed as a a real biopharmaceutical sample to
      confirm the feasibility of our approach for monitoring low levels of oxidation
      variants. 

PMID- 26308167
TI  - Lysophosphatidylcholine attenuates melanoma cell adhesion and migration dependent
      on the degree of fatty acid saturation.

PMID- 26308168
TI  - Ferulic acid alleviates Abeta25-35- and lipopolysaccharide-induced PC12 cellular
      damage: a potential role in Alzheimer's disease by PDE inhibition.
AB  - OBJECTIVE: Phosphodiesterase (PDE) plays an important role in the pathogenesis of
      Alzheimer's disease (AD). Ferulic acid (FA) has a therapeutic benefit in the
      treatment of AD. We investigated whether this therapeutic effect is based on the
      modulation of the PDE/cyclic adenosine monophosphate (cAMP) pathway. In the
      present study, we investigated whether FA could abrogate Abeta25-35- and
      lipopolysaccharide-induced cellular damage. MATERIALS AND METHODS: Cell
      viability, superoxide production, and the levels of inflammatory factors were
      investigated. We further investigated the intracellular levels of cAMP and Ca2+,
      both of which are associated with PDE activity. Furthermore, molecular docking
      was used to identify the binding mode between phosphodiesterase 4B2 (PDE4B2) and
      FA. RESULTS: Pretreatment with FA significantly maintained cell viability,
      increased the levels of superoxide dismutase, and inhibited production of TNF
      alpha and IL-1beta induced by Abeta25-35. Moreover, pretreatment with FA
      increased the intracellular levels of cAMP and decreased the intracellular levels
      of Ca2+. The docking results also showed that FA has the potential to inhibit
      PDE4B2 activity. CONCLUSIONS: Taken together, our results suggested that one of
      the therapeutic effects of FA on AD was potentially mediated by modulating the
      PDE/cAMP pathway.

PMID- 26308169
TI  - Isotretinoin conundrum: a randomized, openlabel, crossover study in Mexico to
      evaluate the bioavailability and bioequivalence of three pharmaceutical
      preparations of isotretinoin in healthy participants.
AB  - OBJECTIVE: The oral retinoid agent isotretinoin (13-cis-retinoic acid) is
      approved for the treatment of severe recalcitrant cystic acne. For registrational
      renewal of Oratane(r) in Mexico (isotretinoin; Laboratorios Dermatologicos Darier
      S.A. de C.V., Mexico), it was necessary to establish bioequivalence to the
      reference product Roaccutan(r) (Isotretinoin; Roche, Mannheim, Germany). Three
      prior studies failed to establish the bioequivalence of Oratane to Mexican
      sourced Roaccutan. However, 13 studies demonstrated the bioequivalence of Oratane
      to Roaccutane(r) from multiple sources. This study compared the bioavailability
      of Oratane with that of Mexicansourced Roaccutan and Australian-sourced
      Roaccutane. METHODS: Study participants received each of the three agents in a
      randomized, open-label, 6-sequence, 3-way crossover study with a 2-week washout
      period between treatments. RESULTS: Pharmacokinetic analysis revealed that peak
      plasma concentration (Cmax) and area under the plasma concentration-time curve
      from time 0 (dosing) to infinite time (AUC0-infinity) were lower for Roaccutan
      than for Roaccutane and Oratane (Cmax: 1,023.35, 1,223.08, and 1,224.25 ng/mL,
      respectively; AUC0-infinity: 13,653.65, 15,681.35 and 15,733.55 ng/mL x h,
      respectively). The 90% CIs (test/reference) for the ratios of the geometric means
      indicated that Oratane was bioequivalent to Roaccutane but not to Roaccutan. In
      addition, Roaccutane (R2) was not bioequivalent to Roaccutan (R1; R1/R2 90% CIs:
      Cmax, 76.12 - 91.04; AUC0-t, 82.19 - 91.13; AUC0-infinity, 82.94 - 91.57).
      CONCLUSION: Oratane and Australian-sourced Roaccutane could be considered
      bioequivalent, but neither formulation was found to be bioequivalent to Mexican
      sourced Roaccutan.

PMID- 26308170
TI  - Pharmacokinetics of trantinterol and its metabolite in healthy elderly and young
      subjects.
AB  - OBJECTIVE: The aim of this study was to investigate and compare the
      pharmacokinetics of trantinterol and its active amphoteric carboxylic acid
      metabolite (1-carbonyl trantinterol) between the healthy elderly and young
      subjects. METHODS: This was a single-center, open-label, parallel-group study
      completed by 22 healthy subjects (>=65 years (the elderly group); 18-45 years
      (the young group); 9 males and 2 females per age group) receiving single oral
      dose of 50 MUg trantinterol tablets. Blood samples were taken at intervals up to
      48 hours post-dose. RESULTS: In both groups, maximum plasma concentration of
      trantinterol was researched at 0.9 hours, while the tmax of 1-carbonyl
      trantinterol differed slightly. Trantinterol Cmax and AUClast were higher in the
      elderly group than the young group, by 27% (90% CI, 0.95-1.69) and 77% (90% CI,
      1.25-2.51), respectively. For 1-carbonyl trantinterol, Cmax, and AUClast were
      also higher, by 36% (90% CI, 1.04-1.78) and 71% (90% CI, 1.27-2.30),
      respectively, in the elderly group. The CL/F and V/F of trantinterol and 1
      carbonyl trantinterol were significantly lower in the elderly group, while t1/2
      of both did not show significant differences. CL/F of trantinterol and 1-carbonyl
      trantinterol were found to significantly correlate inversely with age, and
      positively with the baseline creatinine clearance. CONCLUSIONS: A single dose of
      50 MUg trantinterol was well tolerated. Significant changes in Cmax and AUC of
      trantinterol and 1-carbony trantinterol were seen in the elderly and may be
      clinically important.

PMID- 26308171
TI  - Effect of statins on the mortality and mechanical ventilation duration of acute
      lung injury patients: a meta-analysis of five randomized controlled trials.
AB  - BACKGROUND: Statins have been reported to exert anti-inflammatory effects, but
      the association between statins and acute lung injury (ALI) remains
      controversial. Thus, we performed a meta-analysis of all published randomized
      controlled trials (RCTs) aiming to summarize and evaluate the current evidence
      about the potential use of statins in ALI patients. METHOD: We searched for
      articles that focused on the association between statins and ALI-related outcomes
      through electronic databases until December 10th, 2014. The inclusion of
      articles, quality appraisal of included studies, and data extraction were
      performed by two investigators. Eligible articles were analyzed by Review manager
      5.2 and STATA 12.0 software. RESULTS: Data from 1,778 patients in five randomized
      controlled clinical trials were analyzed. No differences in intensive care unit
      (ICU) mortality (RR=0.88, 95% CI=0.63-1.22, p=0.44), hospital mortality (RR=1.00,
      95% CI=0.85-1.17, p=0.97) and mechanical ventilation duration (MD=-0.40, 95% CI=
      1.52-0.71, p=0.48) were observed between the experimental and control groups.
      CONCLUSIONS: According to large and high-quality published clinical trials as
      also summarized by the present meta-analysis, there is insufficient evidence to
      support the use of statins in ALI patients.

PMID- 26308172
TI  - Propofol-induced rhabdomyolysis: a case report.
AB  - OBJECTIVE: To report a case of propofol-induced rhabdomyolysis. In this case,
      widespread myolysis was detected after induction of anesthesia. CASE SUMMARY: A
      54-year-old female patient was scheduled for a hysterectomy. Beginning shortly
      after the induction of anesthesia with propofol, several episodes of ventricular
      fibrillation occurred. Despite intensive care, the patient failed to recover.
      During most episodes of ventricular fibrillation, marked hyperthermia or
      hyperkalemia were not observed. Unexplained, widespread myolysis affecting both
      skeletal and cardiac muscle was observed at autopsy. DISCUSSION: In this patient,
      the evidence for rhabdomyolysis is robust. Clinical characteristics are similar
      to those observed in propofol infusion syndrome. The absence of a body
      temperature over 40  degrees C precludes the possibility of malignant
      hyperthermia. Widespread rhabdomyolysis locations cannot be explained by
      precordial electric shocks. Propofol is the only drug used in this case that has
      been reported to induce rhabodomyolysis. CONCLUSIONS: Signs of propofol-induced
      rhabdomyolysis may be different from those of malignant hyperthermia. Even a
      regular induction dose of propofol for adults could possibly trigger
      rhabdomyolysis similar to what is observed in children diagnosed with propofol
      infusion syndrome. Though rare, care should still be taken when administering
      propofol.

PMID- 26308173
TI  - Pharmacokinetics of fingolimod and metabolites in subjects with severe renal
      impairment: An open-label, single-dose, parallel-group study.
AB  - OBJECTIVE: This study assessed the pharmacokinetics and tolerability of
      fingolimod and its metabolites in severe renal impairment and healthy subjects.
      METHODS: In this single-dose, open-label study, 9 severe renal impairment
      subjects and 9 demographically matched healthy subjects were included. Each
      subject received a single oral dose of fingolimod 1.25 mg, and their blood and
      urine samples were assessed. The pharmacokinetics of fingolimod and its
      metabolites, fingolimod-phosphate (active metabolite, fingolimod-P), M2, and M3,
      were compared in both groups. Safety and tolerability were also assessed.
      RESULTS: In severe renal impairment subjects, mean+/-standard deviation values of
      Cmax (ng/mL) of fingolimod and fingolimod-P were 0.878+/-0.256 and 1.13+/-0.293
      vs. 0.653+/-0.138 and 0.904+/-0.229 in healthy subjects, respectively. The
      overall drug exposures (AUCinf (ngxh/mL)) for fingolimod and fingolimod-P were
      131+/-90.7 and 75.5+/-33.6 in severe renal impairment subjects vs. 82.3+/-36.9
      and 65.9+/-30.6 in healthy subjects, respectively. t1/2 (hours) for fingolimod
      and fingolimod-P was comparable in severe renal impairment subjects (94+/-53 and
      95+/-50) and healthy subjects (85+/-25 and 101+/-46). All adverse events were as
      expected for fingolimod 1.25 mg. CONCLUSIONS: The exposure to fingolimod and
      fingolimod-P was moderately increased (90% CI, 0.94-2.18) in severe renal
      impairment subjects, while half-lives and protein binding were similar to those
      in healthy subjects. Given that these changes are not clinically meaningful,
      fingolimod dose adjustment is considered unnecessary in patients with mild,
      moderate, or severe renal impairment.

PMID- 26308174
TI  - Pharmacokinetic and pharmacodynamic interaction of siponimod (BAF312) and
      propranolol in healthy subjects.
AB  - OBJECTIVE: To evaluate the cardiac and pulmonary effects of siponimod (BAF312)
      and propranolol co-administration in healthy subjects. METHODS: Healthy subjects
      (n=76) were randomized in a doubleblind manner to receive propranolol at
      siponimod steady state (group A), siponimod at propranolol steady state (group
      B), placebo (group C) and propranolol (group D). Pharmacodynamic evaluations
      included maximum change from baseline in time-matched hourly average heart rate
      (Emax HR) and mean arterial blood pressure (Emax MABP) over 24 hours postdose,
      change from baseline in PR intervals, cardiac rhythm, and forced expiratory
      volume in 1 second (FEV1). Pharmacokinetic and safety parameters were also
      assessed. RESULTS: Siponimod and propranolol when administered alone resulted in
      similar HR decrease at steady state. Compared to propranolol alone, the
      combination at steady state had an additional 6.21 bpm (95%CI: 2.32, 10.11)
      decrease of mean EmaxHR, a decrease of 5.04 bpm (0.52, 9.56) for group A and 7.39
      bpm (2.87, 11.90) for group B. A minor decrease in MABP and a trend towards PR
      interval increase were noted with co-administration treatment vs. propranolol
      alone. There were no episodes of second-degree atrioventricular blocks or sinus
      pauses>3 seconds. Baseline-corrected FEV1 was reduced by -0.07 L (95% CI: -0.17,
      0.03) for group A and -0.05 L (-0.15, 0.05) for group B vs. propranolol alone.
      There were no cardiovascular adverse events during coadministration treatment.
      CONCLUSIONS: Coadministration of siponimod and propranolol was well tolerated.
      Bradyarrhythmic effects were less pronounced when propranolol was added to
      siponimod steady-state therapy compared with siponimod addition to propranolol.

PMID- 26308175
TI  - Population pharmacokinetics of tenofovir in HIV/HBV co-infected patients.
AB  - OBJECTIVE: Tenofovir is an efficacious drug with a long half-life and high
      activity against both HIV and HBV. However, the pharmacokinetics of tenofovir
      have not been studied in HIV/HBV co-infected patients. Data from HIV mono
      infected patients may not be transferable to HIV/HBV co-infected population
      because the nature and consequences of the co-infection are different. This study
      developed a population pharmacokinetic model of tenofovir in patients with
      HIV/HBV co-infection and identified pathophysiologic factors that affect the
      pharmacokinetics of the drug. METHODS: Sparse and intensive blood samples were
      collected from patients with HIV/HVB coinfection. The population pharmacokinetic
      model of tenofovir was developed by a nonlinear mixed-effects modeling approach
      (NONMEM(r)). RESULTS: A total of 332 tenofovir plasma concentrations from 146
      patients were obtained. A two-compartment model best described the
      pharmacokinetics of tenofovir. Creatinine clearance (estimated by Cockcroft and
      Gault equation) affected the tenofovir apparent clearance (CL/F). Tenofovir CL/F
      decreased by 23.5% when concomitantly used with atazanavir/ritonavir.
      CONCLUSIONS: Based on the results from our study, it was shown that the
      pharmacokinetics of tenofovir in HIV/HBV co-infected patients are comparable to
      those with HIVmonoinfection. This study confirmed that patients with kidney
      impairment and the concurrent use of atazanavir/ritonavir will require the dosage
      of tenofovir to be adjusted to ensure efficacy and prevent unwanted toxicities.
      The developed model can reliably be used to adjust for the dosage of tenofovir in
      this population, especially when therapeutic drug monitoring services are
      unavailable.

PMID- 26308176
TI  - Lack of effect of favipiravir, a novel antiviral agent, on QT interval in healthy
      Japanese adults.
AB  - OBJECTIVE: A thorough QT study of favipiravir, a novel antiviral agent, was
      conducted using a randomized, doubleblind, 4-group, 4-period crossover, placebo
      and positive-controlled (open-label moxifloxacin) design. MATERIALS AND METHODS:
      56 healthy Japanese adults of both sexes received single oral doses of
      favipiravir 1,200 and 2,400 mg (Avigan(r) Tablets, Toyama Chemical Co., Ltd.),
      moxifloxacin 400 mg, and a placebo. QT intervals after these treatments were
      measured under blinded conditions. The primary endpoint was the time-matched,
      placebo-adjusted change in corrected QT intervals using the Fridericia method
      (QTcF) from predose for favipiravir or moxifloxacin (DeltaDeltaQTcF). RESULTS:
      Lower bounds of the two-sided 90% confidence interval of DeltaDeltaQTcF values
      for moxifloxacin exceeded 3 msec at all time points, and the maximum value was
      14.0 (11.8-16.1, 90% confidence interval) msec at 3 hours after administration.
      Similarly, maximum DeltaDeltaQTcF values for favipiravir were 0.833 (-1.33-3.00)
      msec at 3 hours after administration of 1,200 mg, and 0.500 (-1.88-2.88) msec at
      6 hours after administration of 2,400 mg. Calculation of the sample size using
      the DeltaDeltaQTcF value of moxifloxacin indicated that 25 subjects would be
      sufficient for detection at a power of 90% or higher, which meets the criteria
      for assuring assay sensitivity. CONCLUSIONS: It is possible to use a smaller
      number of subjects in thorough QT studies in Japan than in Europe and the US
      utilizing moxifloxacin as a positive control. There were no detectable effects of
      favipiravir on the QT/QTc interval.

PMID- 26308177
TI  - Potentially inappropriate medication use at ambulatory care visits by elderly
      patients covered by National Health Insurance in Korea.
AB  - OBJECTIVES: Potentially inappropriate medication (PIM) use is an important and
      preventable safety concern in the care of elderly patients and has been
      associated with adverse drug reactions, hospitalization, and mortality. Although
      PIM use for the elderly is a common and serious public health issue worldwide,
      there are few studies examining PIM use in the ambulatory care setting in Korea.
      METHODS: To examine the prevalence and risk factors of PIM use from ambulatory
      care visits by elderly patients covered by National Health Insurance (NHI) in
      Korea, the nationwide prescription claims data of elderly patients' ambulatory
      care visits in 2006 were analyzed. RESULTS: Potentially inappropriate
      prescriptions were identified using extensive criteria that included Beers',
      Zhan's, and Canadian criteria. In 2006, 3,770,978 elderly patients received
      40,995,267 prescriptions. 36.7% of the total prescriptions for elderly patients
      who visited ambulatory care clinics were identified as PIM use. Findings in this
      study indicated that the strongest risk factors for PIM prescriptions were the
      number of drugs prescribed and visit characteristics. CONCLUSION: Therefore, it
      is necessary to develop the explicit criteria of PIM prescription in Korea that
      can be included in the Drug Utilization Review (DUR) system, which is expected to
      lead to more appropriate and judicious prescribing.

PMID- 26308178
TI  - Efficacy of calcitriol compared to alfacalcidol for the treatment of secondary
      hyperparathyroidism in peritoneal dialysis patients.

PMID- 26308179
TI  - Effects of Acute Carnosine and beta-Alanine on Isometric Force and Jumping
      Performance.
AB  - PURPOSE: To assess the effects of acute combined L-carnosine and beta-alanine
      (Carn-BA) supplementation on isometric and dynamic tasks. METHODS: Twelve healthy
      participants performed knee-extensor maximal voluntary contractions (MVCs) and
      countermovement jumps (CMJs) before and after a fatiguing protocol (45-s
      continuous CMJs). Isometric and dynamic tests were performed 4 h after ingestion
      of Carn-BA (2 g of L-carnosine and 2 g of beta-alanine) or placebo (PLA), in
      random order. After the fatiguing protocol, blood lactate concentration ([La-]),
      general and muscular rating of perceived exertion (RPE), and muscle pain (24 and
      48 h after the end of the fatiguing protocol) were assessed. RESULTS: During the
      fatiguing protocol, significant decreases in jump height and increases in contact
      time were found in both groups from the 15th second onward to the end of the
      fatiguing protocol. Average contact time and jump height were respectively lower
      (-7%; P = .018) and higher (+6%; P = .025) in Carn-BA than in PLA. After the
      fatiguing protocol, MVC decreased in both PLA and Carn-BA, but it was higher in
      Carn-BA than in PLA (+15%, P = 0.012), while CMJ did not change. Moreover,
      general RPE was lower and muscle pain at 24 h was higher in Carn-BA than in PLA,
      whereas muscle RPE and [La-] did not differ between conditions. CONCLUSIONS:
      Ingesting Carn-BA before exercise induced positive effects on MVC and CMJ after
      the fatiguing protocol and improved CMJ performance during the 45-s continuous
      jumping effort, even when acutely supplemented. Furthermore, Carn-BA reduced the
      general RPE and increased muscle pain 24 h after the fatiguing task.

PMID- 26308180
TI  - Going Out on a Limb: Delineating The Effects of beta-Branching, N-Methylation,
      and Side Chain Size on the Passive Permeability, Solubility, and Flexibility of
      Sanguinamide A Analogues.
AB  - It is well established that intramolecular hydrogen bonding and N-methylation
      play important roles in the passive permeability of cyclic peptides, but other
      structural features have been explored less intensively. Recent studies on the
      oral bioavailability of the cyclic heptapeptide sanguinamide A have raised the
      question of whether steric occlusion of polar groups via beta-branching is an
      effective, yet untapped, tool in cyclic peptide permeability optimization. We
      report the structures of 17 sanguinamide A analogues designed to test the
      relative contributions of beta-branching, N-methylation, and side chain size to
      passive membrane permeability and aqueous solubility. We demonstrate that beta
      branching has little effect on permeability compared to the effects of aliphatic
      carbon count and N-methylation of exposed NH groups. We highlight a new N
      methylated analogue of sanguinamide A with a Leu substitution at position 2 that
      exhibits solvent-dependent flexibility and improved permeability over that of the
      natural product. 

PMID- 26308182
TI  - Perceptual dimensions differentiate emotions.
AB  - Individuals often describe objects in their world in terms of perceptual
      dimensions that span a variety of modalities; the visual (e.g., brightness: dark
      bright), the auditory (e.g., loudness: quiet-loud), the gustatory (e.g., taste:
      sour-sweet), the tactile (e.g., hardness: soft vs. hard) and the kinaesthetic
      (e.g., speed: slow-fast). We ask whether individuals use perceptual dimensions to
      differentiate emotions from one another. Participants in two studies (one where
      respondents reported on abstract emotion concepts and a second where they
      reported on specific emotion episodes) rated the extent to which features
      anchoring 29 perceptual dimensions (e.g., temperature, texture and taste) are
      associated with 8 emotions (anger, fear, sadness, guilt, contentment, gratitude,
      pride and excitement). Results revealed that in both studies perceptual
      dimensions differentiate positive from negative emotions and high arousal from
      low arousal emotions. They also differentiate among emotions that are similar in
      arousal and valence (e.g., high arousal negative emotions such as anger and
      fear). Specific features that anchor particular perceptual dimensions (e.g., hot
      vs. cold) are also differentially associated with emotions.

PMID- 26308183
TI  - Linking CO2 Sorption Performance to Polymer Morphology in Aminopolymer/Silica
      Composites through Neutron Scattering.
AB  - Composites of poly(ethylenimine) (PEI) and mesoporous silica are effective,
      reversible adsorbents for CO2, both from flue gas and in direct air-capture
      applications. The morphology of the PEI within the silica can strongly impact the
      overall carbon capture efficiency and rate of saturation. Here, we directly probe
      the spatial distribution of the supported polymer through small-angle neutron
      scattering (SANS). Combined with textural characterization from physisorption
      analysis, the data indicate that PEI first forms a thin conformal coating on the
      pore walls, but all additional polymer aggregates into plug(s) that grow along
      the pore axis. This model is consistent with observed trends in amine-efficiency
      (CO2/N binding ratio) and pore size distributions, and points to a trade-off
      between achieving high chemical accessibility of the amine binding sites, which
      are inaccessible when they strongly interact with the silica, and high
      accessibility for mass transport, which can be hampered by diffusion through PEI
      plugs. We illustrate this design principle by demonstrating higher CO2 capacity
      and uptake rate for PEI supported in a hydrophobically modified silica, which
      exhibits repulsive interactions with the PEI, freeing up binding sites. 

PMID- 26308184
TI  - Metal-Polycyclic Aromatic Hydrocarbon Mixture Toxicity in Hyalella azteca. 2.
      Metal Accumulation and Oxidative Stress as Interactive Co-toxic Mechanisms.
AB  - Mixtures of metals and polycyclic aromatic hydrocarbons (PAHs) are commonly found
      in aquatic environments. Emerging reports have identified that more-than-additive
      mortality is common in metal-PAH mixtures. Individual aspects of PAH toxicity
      suggest they may alter the accumulation of metals and enhance metal-derived
      reactive oxygen species (ROS). Redox-active metals (e.g., Cu and Ni) are also
      capable of enhancing the redox cycling of PAHs. Accordingly, we explored the
      mutual effects redox-active metals and PAHs have on oxidative stress, and the
      potential for PAHs to alter the accumulation and/or homeostasis of metals in
      juvenile Hyalella azteca. Amphipods were exposed to binary mixtures of Cu, Cd,
      Ni, or V, with either phenanthrene (PHE) or phenanthrenequinone (PHQ). Mixture of
      Cu with either PAH produced striking more-than-additive mortality, whereas all
      other mixtures amounted to strictly additive mortality following 18-h exposures.
      We found no evidence to suggest that interactive effects on ROS production were
      involved in the more-than-additive mortality of Cu-PHE and Cu-PHQ mixtures.
      However, PHQ increased the tissue concentration of Cu in juvenile H. azteca,
      providing a potential mechanism for the observed more-than-additive mortality.

PMID- 26308181
TI  - Multifunctional Nanoparticles Facilitate Molecular Targeting and miRNA Delivery
      to Inhibit Atherosclerosis in ApoE(-/-) Mice.
AB  - The current study presents an effective and selective multifunctional
      nanoparticle used to deliver antiatherogenic therapeutics to inflamed pro
      atherogenic regions without off-target changes in gene expression or particle
      induced toxicities. MicroRNAs (miRNAs) regulate gene expression, playing a
      critical role in biology and disease including atherosclerosis. While anti-miRNA
      are emerging as therapeutics, numerous challenges remain due to their potential
      off-target effects, and therefore the development of carriers for selective
      delivery to diseased sites is important. Yet, co-optimization of multifunctional
      nanoparticles with high loading efficiency, a hidden cationic domain to
      facilitate lysosomal escape and a dense, stable incorporation of targeting
      moieties is challenging. Here, we create coated, cationic lipoparticles (CCLs),
      containing anti-miR-712 (~1400 molecules, >95% loading efficiency) within the
      core and with a neutral coating, decorated with 5 mol % of peptide (VHPK) to
      target vascular cell adhesion molecule 1 (VCAM1). Optical imaging validated
      disease-specific accumulation as anti-miR-712 was efficiently delivered to
      inflamed mouse aortic endothelial cells in vitro and in vivo. As with the naked
      anti-miR-712, the delivery of VHPK-CCL-anti-miR-712 effectively downregulated the
      d-flow induced expression of miR-712 and also rescued the expression of its
      target genes tissue inhibitor of metalloproteinase 3 (TIMP3) and reversion
      inducing-cysteine-rich protein with kazal motifs (RECK) in the endothelium,
      resulting in inhibition of metalloproteinase activity. Moreover, an 80% lower
      dose of VHPK-CCL-anti-miR-712 (1 mg/kg dose given twice a week), as compared with
      naked anti-miR-712, prevented atheroma formation in a mouse model of
      atherosclerosis. While delivery of naked anti-miR-712 alters expression in
      multiple organs, miR-712 expression in nontargeted organs was unchanged following
      VHPK-CCL-anti-miR-712 delivery. 

PMID- 26308186
TI  - A Mechanistic Explanation of the Peculiar Amphiphobic Properties of Hybrid
      Organic-Inorganic Coatings by Combining XPS Characterization and DFT Modeling.
AB  - We report a combined X-ray photoelectron spectroscopy and theoretical modeling
      analysis of hybrid functional coatings constituted by fluorinated alkylsilane
      monolayers covalently grafted on a nanostructured ceramic oxide (Al2O3) thin film
      deposited on aluminum alloy substrates. Such engineered surfaces, bearing hybrid
      coatings obtained via a classic sol-gel route, have been previously shown to
      possess amphiphobic behavior (superhydrophobicity plus oleophobicity) and
      excellent durability, even under simulated severe working environments. Starting
      from XPS, SEM, and contact angle results and analysis, and combining it with DFT
      results, the present investigation offers a first mechanistic explanation at a
      molecular level of the peculiar properties of the hybrid organic-inorganic
      coating in terms of composition and surface structural arrangements. Theoretical
      modeling shows that the active fluorinated moiety is strongly anchored on the
      alumina sites with single Si-O-Al bridges and that the residual valence of Si is
      saturated by Si-O-Si bonds which form a reticulation with two vicinal
      fluoroalkylsilanes. The resulting hybrid coating consists of stable rows of
      fluorinated alkyl chains in reciprocal contact, which form well-ordered and
      packed monolayers. 

PMID- 26308187
TI  - Modulation of bone marrow microenvironment following ruxolitinib therapy in
      myelofibrosis.

PMID- 26308189
TI  - Correction: Alternating Antibiotics Render Resistant Bacteria Beatable.

PMID- 26308188
TI  - Choroidal Thickness in Turkish Children with Anisometric Amblyopia.
AB  - PURPOSE: To assess macular choroidal thickness (CT) and axial length measurements
      in children with anisometropic amblyopia and to compare the measurements with
      that of fellow non-amblyopic eyes and age-sex matched controls. METHODS: Forty
      patients with anisometropic amblyopia and 40 age-/sex-matched controls were
      evaluated in this study. Eyes were classified into three groups as follows:
      amblyopic eyes (n = 40), fellow non-amblyopic eyes, and healthy eyes (n = 40).
      All subjects underwent complete ophthalmic examination and macular choroidal
      thickness measurements by enhanced depth imaging method of the Spectralis optical
      coherence tomography system. CT was measured at the fovea and at 1000-MUm
      intervals from the foveal center in both temporal and nasal directions. The
      statistical assessment was performed with the assistance of one-way analysis of
      variance (ANOVA) and Pearson's correlation test. RESULTS: The mean subfoveal CT
      was 389.35, 349.07, and 315.8 MUm in the amblyopic, fellow non-amblyopic and
      healthy eyes, respectively. Choroid was thickest in subfoveal and thinnest in
      nasal regions among all groups. Both amblyopic and fellow non-amblopic eyes were
      more hyperopic than healthy eyes. While the subfoveal and nasal CT in amblyopic
      eyes and fellow eyes were significantly higher than healthy eyes, the temporal CT
      in amblyopic eyes was significantly higher than in healthy eyes. There was a
      significant positive correlation between the CT of the subfoveal, nasal, and
      temporal regions and the refractive state (r = 0.432 p = 0.001; r = 0.324 p =
      0.001; r = 0.215 p = 0.01, respectively). CONCLUSION: The macular choroidal
      thickness-not only in amblyopic eyes but also in non-amblyopic fellow eyes-was
      significantly thicker than in the healthy subjects. The thick choroid in
      amblyopic and non-amblyopic fellow eyes may indicate bilateral delay of
      emmetropization, which probably means amblyopia affecting the visual feedback of
      both eyes.

PMID- 26308190
TI  - Trauma-Related Altered States of Consciousness (TRASC) and Functional Impairment
      II: Perceived Causal Relationships in an Online Sample.
AB  - Research supports the existence of a dissociative subtype of posttraumatic stress
      disorder, although studies have not directly compared the perceived impact of
      dissociative versus nondissociative posttraumatic symptoms on social and
      occupational functioning. In addition, research is beginning to differentiate
      between posttraumatic distress associated with normal waking consciousness (NWC)
      and dissociative experiences of trauma-related altered states of consciousness
      (TRASC) along multiple phenomenological dimensions. The current study
      investigated perceived causal relationships between posttraumatic symptoms
      associated with NWC-distress and TRASC on the one hand and interpersonal and
      occupational functioning on the other. Although both TRASC and NWC-distress
      independently accounted for variance in self-reported interpersonal and
      occupational problems, perceived causal relationship results showed that
      individuals tended to attribute their social and work-related problems more
      strongly to NWC-distress than to TRASC. Future research directions are discussed.

PMID- 26308191
TI  - Analysis of cigarette smoking mechanism by real time video-endoscopic
      documentation.
AB  - OBJECTIVE: To view, document and analyze the smoking mechanism as seen via video
      endoscopic examination during the action of cigarette smoking. STUDY DESIGN:
      Observational study. METHODS: Twenty-two healthy smoking volunteers were examined
      with a trans-nasal video-laryngoscope while breathing, sniffing and cigarette
      smoking. Smoking a whole cigarette was recorded in each participant. The
      different stages of smoking were defined and their duration was measured. The
      glottic opening angle was calculated during breathing, sniffing and smoking.
      RESULTS: A smoking cycle with four distinct stages was recognized. The stages
      included an oral smoke accumulation, pharyngo-laryngeal jet inhalation,
      infralaryngeal spread, and finally humidified exhalation stage. The stages' mean
      duration was 1.93(+/-1.21), 0.39(+/-0.31), 2.00(+/-1.12) and 4.5(+/-2.70)
      seconds, respectively. The glottic opening angle during smoke inhalation was
      wider in 16% (p = 0.02) compared to normal inhalation during breathing. The
      glottic opening during smoke exhalation was comparable to what was observed
      during normal exhalation. The reduction in the glottic opening was more
      significant during the action of smoking compared with normal breathing (p =
      0.042). CONCLUSIONS: Smoking follows a consistent sequence of events, defined by
      specific anatomic configuration and relatively persistent duration. The fast
      turbulent flow of the smoke over the narrow glottic aperture and at the areas of
      bifurcation at the trachea and bronchi may have a role in the high relative risk
      for carcinoma in these areas.

PMID- 26308192
TI  - Reduction in Neisseria meningitidis infection in Italy after Meningococcal C
      conjugate vaccine introduction: A time trend analysis of 1994-2012 series.
AB  - The incidence of invasive meningococcal disease (IMD) in Italy is among the
      lowest in Europe. Meningococcal C conjugate vaccine (MCC) was introduced in 2005
      for 12 months old infants. The aim of this study was to describe the epidemiology
      of IMD in Italy from 1994 to 2012 and to evaluate the impact of MCC introduction.
      Data about Neisseria meningitidis (N. meningitidis) cases were drawn from the
      National Surveillance of Invasive Bacterial Diseases. The average incidence of
      IMD during 1994-2012 in Italy was 0.36 per 100,000 (95%CI 0.30; 0.40). N.
      meningitidis B was the most frequent serogroup and infants less than 12 months
      old were the most affected. Joinpoint analysis showed a statistically significant
      reduction in the incidence of N. meningitidis C related IMD after MCC
      introduction: the Annual Percentage Change declined from 21.8 (95%CI 15.1; 28.9)
      in 1994-2005 to -19.9 (95%CI -28.2; -10.7) afterwards. No changes were observed
      with respect to N. meningitidis B related IMD. Poisson regression showed a
      statistically significant reduction in the incidence of IMD both associated to N.
      meningitidis C (Incidence Rate Ratio 0.33; 95%CI 0.29; 0.37) and due to all
      serogroups (Incidence Rate Ratio 0.70; 95%CI 0.65; 0.75) in the post-vaccination
      period compared to the pre-vaccination one. On the other hand, the incidence of
      N. meningitidis B related IMD did not decrease. Our results suggest that MCC had
      an impact in decreasing the incidence of N. meningitidis C related IMD. However,
      data on typing are incomplete and efforts are needed to make them available for
      studying the need and the impact of other meningococcal vaccines.

PMID- 26308194
TI  - Exploring the biological consequences of conformational changes in aspartame
      models containing constrained analogues of phenylalanine.
AB  - The dipeptide aspartame (Asp-Phe-OMe) is a sweetener widely used in replacement
      of sucrose by food industry. 2',6'-Dimethyltyrosine (DMT) and 2',6'
      dimethylphenylalanine (DMP) are two synthetic phenylalanine-constrained
      analogues, with a limited freedom in chi-space due to the presence of methyl
      groups in position 2',6' of the aromatic ring. These residues have shown to
      increase the activity of opioid peptides, such as endomorphins improving the
      binding to the opioid receptors. In this work, DMT and DMP have been synthesized
      following a diketopiperazine-mediated route and the corresponding aspartame
      derivatives (Asp-DMT-OMe and Asp-DMP-OMe) have been evaluated in vivo and in
      silico for their activity as synthetic sweeteners. 

PMID- 26308195
TI  - Role of salpingectomy at the time of urogynecologic surgery.
AB  - PURPOSE OF REVIEW: This article reviews the current literature about prophylactic
      bilateral salpingectomy and provides guidelines for clinicians in regard to the
      inclusion of salpingectomy at the time of urogynecologic surgery. RECENT
      FINDINGS: After the Nurses' Health Study showed that all-cause mortality was
      increased in women undergoing oophorectomy at the time of hysterectomy for benign
      indications, there was a shift in focus toward ovarian conservation at the time
      of gynecologic surgery. As there has been continued interest in the fallopian
      tube as the origin of ovarian cancer, a move toward prophylactic salpingectomy
      has occurred. This strategy has become widely accepted in high-risk women, but is
      not universal in either premenopausal or postmenopausal women who are primarily
      served by the urogynecologic community. SUMMARY: Current literature supports
      that, if easily accessible, the fallopian tubes should be removed at the time of
      urogynecologic surgery. In premenopausal women, salpingectomy does not likely
      affect ovarian reserve, but this possibility should be discussed with patients.
      If inaccessible (i.e., at the time of a midurethral sling), there should not be
      additional surgery performed to access the fallopian tubes. In addition, the
      pathologic evaluation of the fallopian tubes should include complete examination
      of the fimbriae and a representative section of the nonfimbriated portion.

PMID- 26308196
TI  - New developments in therapies for fecal incontinence.
AB  - PURPOSE OF REVIEW: Fecal incontinence is a common problem among women, affecting
      between 2 and 7% of the general population. Although pelvic reconstructive
      surgeons have had many effective tools and techniques to treat other pelvic floor
      disorders, including pelvic organ prolapse and urinary incontinence, there has
      been a shortage of effective treatment options for fecal incontinence. RECENT
      FINDINGS: In the past few years, however, we have witnessed the introduction of
      several novel and intriguing treatments for this socially disabling condition.
      This renaissance of innovation speaks to the recognition that fecal incontinence
      is a significant pelvic floor disorder that we have not adequately addressed.
      Recent studies include research on a novel vaginal device to treat fecal
      incontinence, as well as long-term and comparative studies on neuromodulation,
      perianal bulking and transanal radiofrequency energy. There have also been recent
      studies on several novel, yet still unapproved, implantable devices, including a
      self-affixing rectal sling and a magnetic sphincter. SUMMARY: In the not-too
      distant future, it appears that pelvic reconstructive surgeons will have a vast
      armamentarium of tools to manage one of the more vexing pelvic floor conditions
      we face in our daily practice. With the introduction of these new treatments, it
      will be important to develop a logical algorithm in our approach to fecal
      incontinence.

PMID- 26308197
TI  - New evidence in the treatment of overactive bladder.
AB  - PURPOSE OF REVIEW: Overactive bladder (OAB) in women is highly prevalent. It can
      be very bothersome and affect quality of life. Treatment differs significantly
      depending on the clinical presentation, and includes behavioural modification,
      medicinal therapies and surgical procedures. New treatment options have become
      available in recent years, and can offer great benefit to patients with
      persistent, bothersome OAB. RECENT FINDINGS: First-line management for OAB
      consists of lifestyle and behavioural therapy, followed by antimuscarinic therapy
      or oral beta-3 agonists. Sacral neuromodulation, onabotulinumtoxinA and posterior
      tibial nerve stimulation are additional well tolerated and efficacious treatment
      options that should be considered in carefully selected, refractory OAB patients.
      These recent advances in OAB therapy are discussed in this review. SUMMARY: The
      treatment of OAB is often complex, and can require trials of multiple different
      treatment modalities. Although the treatment advances discussed in this review
      have augmented treatment of OAB, the condition continues to negatively impact
      quality of life for our ageing female population. Clinical trials and development
      of novel therapies continue to be paramount.

PMID- 26308198
TI  - Epidemiological trends and future care needs for pelvic floor disorders.
AB  - PURPOSE OF REVIEW: We sought to provide a review of the recent literature
      regarding the prevalence and epidemiological trends in pelvic floor disorders
      (PFDs) including pelvic organ prolapse (POP), urinary incontinence and fecal
      incontinence. We also examined the current trends in surgical treatment for these
      disorders and discuss future care needs. RECENT FINDINGS: Approximately, one
      quarter of all women suffer from at least one or more PFDs. Urinary incontinence
      represents the most common PFD with an estimated prevalence of 15-17%, whereas
      fecal incontinence affects, approximately, 9% of adult women. POP is more
      difficult to assess with prevalence estimates ranging from 3 to 8%. Surgery for
      PFDs is common as 20% of women undergo stress urinary incontinence or POP surgery
      over their lifetime. As the aging population grows, the number of women with PFDs
      will increase substantially and the demand for care for these disorders will
      continue to grow through the year 2050. SUMMARY: PFDs are a significant public
      health issue and they negatively impact the lives of millions of adult women. The
      projected increase in the number of women affected by PFDs over the next 40 years
      will create increased demand for providers properly trained in Female Pelvic
      Medicine and Reconstructive Surgery.

PMID- 26308199
TI  - Midurethral slings: which should I choose and what is the evidence for use?
AB  - PURPOSE OF REVIEW: Midurethral slings are currently the most commonly performed
      surgeries for stress urinary incontinence (SUI). This review examines the pros
      and cons of the main types of midurethral slings that are available for the
      surgical treatment of SUI - full-length retropubic, full-length transobturator,
      and single-incision slings - to assist patients and physicians in choosing
      between them. RECENT FINDINGS: Comparative studies have shown that full-length
      retropubic and transobturator midurethral slings have similar efficacy but differ
      in their risk profiles; retropubic slings have higher rates of bladder
      perforation whereas transobturator slings have more groin pain and dyspareunia.
      When a certain type of single-incision sling is excluded from systematic reviews,
      single-incision slings appear comparable to standard midurethral slings. SUMMARY:
      Both full-length midurethral slings - retropubic and transobturator - are
      reasonable for the surgical treatment of SUI. The decision to choose one or the
      other should be individualized based on patient preference after counseling about
      the risks of each. More recent data suggest that the currently available single
      incision slings may be comparable.

PMID- 26308200
TI  - Sex trafficking of adolescents and young adults in the United States: healthcare
      provider's role.
AB  - PURPOSE OF REVIEW: Sex trafficking of adolescents and young adults is both a
      human rights violation and a public health problem, globally and in the United
      States. Healthcare providers, including obstetricians and gynecologists, interact
      with victims, often while they remain under their traffickers' control, but
      because of providers' lack of training in identification and response many
      victims go unrecognized and unaided. This review provides an overview of the
      definitions of sex trafficking and commercial sexual exploitation, contributing
      factors, health consequences, recruitment of victims, and identification and
      response by healthcare providers. RECENT FINDINGS: The literature on definitions
      and risk factors associated with sex trafficking is growing; however, literature
      on healthcare providers' role in addressing sex trafficking remains more limited.
      It is increasingly recognized that healthcare providers have an important role in
      victim identification and response and as advocates, collaborating with national,
      regional, and local agencies to increase awareness of sex trafficking as a public
      health problem and to address the needs of adolescent and young adult victims and
      survivors globally and in the United States. SUMMARY: As professionals who
      interact with adolescent and young adult victims of sex trafficking, healthcare
      providers have an important role: in collaboration with other professionals and
      agencies they can help to identify, respond to, extricate, protect, and advocate
      for victims and survivors.

PMID- 26308201
TI  - Apical prolapse repair: weighing the risks and benefits.
AB  - PURPOSE OF REVIEW: This article reviews the current literature regarding surgical
      repair of vaginal apical prolapse and discusses the risks and benefits of various
      surgical approaches. RECENT FINDINGS: Vaginal uterosacral ligament suspension has
      similar anatomic and subjective outcomes to sacrospinous ligament fixation at 1
      year. Native tissue vaginal repairs offer decreased morbidity compared with mesh
      augmented sacrocolpopexy; however, sacrocolpopexy has greater anatomic success.
      Minimally invasive sacrocolpopexy appears to be equivalent to open abdominal
      sacrocolpopexy. Native tissue repairs and transvaginal mesh kits support the
      vaginal apex with similar results; however, long-term follow-up is needed.
      Robotic and laparoscopic sacrocolpopexy are equally effective in restoring the
      vaginal apex. SUMMARY: Surgical restoration of the vaginal apex can be
      accomplished via a variety of approaches and techniques. When deciding on the
      proper surgical intervention, the surgeon must carefully calculate the risks and
      benefits of each procedure while incorporating the patient's individual medical
      and surgical risk factors. Lastly, a discussion regarding the patient's overall
      goals of care is paramount to the decision-making process.

PMID- 26308202
TI  - A gynaecologic perspective on cloacal malformations.
AB  - PURPOSE OF REVIEW: Advances in surgical reconstruction of cloacal malformations
      have led to better functional outcomes and quality of life. As a result,
      adolescents and women born with these complex malformations will have the same
      aspirations as their peers including sexual relationships and fertility. RECENT
      FINDINGS: Currently, there is a paucity of data on gynaecologic outcomes and
      sexual function, and obstetric data are limited primarily to case reports. Making
      evidence-based clinical recommendations is difficult for gynaecologic providers.
      Unique gynaecologic issues can arise in infancy, adolescence or adulthood.
      Recognition and appropriate management of these complications is imperative to
      maximize sexual esteem and preserve future fertility. Pregnancy requires adequate
      prenatal preparation and specialized multidisciplinary care under an experienced
      obstetrician and urologist. SUMMARY: This review highlights the issues that may
      be encountered in providing gynaecologic care to patients with cloacal
      malformations, presents the available literature to provide informative evidence
      and identifies gaps in knowledge in order to suggest potential future research
      opportunities.

PMID- 26308203
TI  - Dermoid cysts in adolescents.
AB  - PURPOSE OF REVIEW: Dermoid ovarian cysts, or mature cystic teratomas, are the
      most common benign ovarian neoplasms found in adolescents and they continue to
      challenge clinicians about correct management and treatment. RECENT FINDINGS:
      Laparoscopic treatment for large cysts is usually the preferred method with
      ovarian preservation. Cyst rupture and recurrence still remain potential risks of
      this surgical approach. Torsion can occur frequently in the population and when
      it occurs, fertility-sparing treatment should be attempted. SUMMARY: Physicians
      should understand the major controversies surrounding management of dermoid cysts
      and the importance of preserving future fertility.

PMID- 26308204
TI  - Gender-neutrality, herd effect and resilient immune response for sustainable
      impact of HPV vaccination.
AB  - PURPOSE OF REVIEW: This review summarize the impact of various strategies of
      human papillomavirus (HPV) vaccination, such as vaccinating only girls or both
      girls and boys. RECENT FINDINGS: Slow and inefficient implementation of HPV
      vaccination programmes has delayed the impact of the first human cancer vaccine.
      Vaccinating only girls, with a rather low coverage, has led to a limited herd
      effect and, thus, not full use of the HPV vaccine potential. SUMMARY: Gender
      neutral vaccination based on comparative effectiveness research will hopefully
      soon tackle the whole spectrum of HPV cancers in both sexes. The remaining
      challenges are how to ensure resilience of HPV vaccine-induced immunity and herd
      effect to guarantee population-level impact of HPV vaccination, and how to guard
      against HPV type replacement.

PMID- 26308206
TI  - Patterns of Protein Evolution in Cytochrome c Oxidase 1 (COI) from the Class
      Arachnida.
AB  - Because sequence information is now available for the 648bp barcode region of
      cytochrome c oxidase 1 (COI) from more than 400,000 animal species, this gene
      segment can be used to probe patterns of mitochondrial evolution. The present
      study examines levels of amino acid substitution and the frequency of indels in
      COI from 4177 species of arachnids, including representatives from all 16 orders
      and 43% of its families (267/625). It examines divergences at three taxonomic
      levels-among members of each order to an outgroup, among families in each order
      and among BINs, a species proxy, in each family. Order Distances vary fourfold
      (0.10-0.39), while the mean of the Family Distances for the ten orders ranges
      fivefold (0.07-0.35). BIN Distances show great variation, ranging from 0.01 or
      less in 12 families to more than 0.25 in eight families. Patterns of amino acid
      substitution in COI are generally congruent with previously reported variation in
      nucleotide substitution rates in arachnids, but provide some new insights, such
      as clear rate acceleration in the Opiliones. By revealing a strong association
      between elevated rates of nucleotide and amino acid substitution, this study
      builds evidence for the selective importance of the rate variation among arachnid
      lineages. Moreover, it establishes that groups whose COI genes have elevated
      levels of amino acid substitution also regularly possess indels, a dramatic form
      of protein reconfiguration. Overall, this study suggests that the mitochondrial
      genome of some arachnid groups is dynamic with high rates of amino acid
      substitution and frequent indels, while it is 'locked down' in others. Dynamic
      genomes are most prevalent in arachnids with short generation times, but the
      possible impact of breeding system deserves investigation since many of the
      rapidly evolving lineages reproduce by haplodiploidy, a mode of reproduction
      absent in 'locked down' taxa. 

PMID- 26308205
TI  - Regional Homogeneity of Resting-State Brain Activity Suppresses the Effect of
      Dopamine-Related Genes on Sensory Processing Sensitivity.
AB  - Sensory processing sensitivity (SPS) is an intrinsic personality trait whose
      genetic and neural bases have recently been studied. The current study used a
      neural mediation model to explore whether resting-state brain functions mediated
      the effects of dopamine-related genes on SPS. 298 healthy Chinese college
      students (96 males, mean age = 20.42 years, SD = 0.89) were scanned with magnetic
      resonance imaging during resting state, genotyped for 98 loci within the dopamine
      system, and administered the Highly Sensitive Person Scale. We extracted a "gene
      score" that summarized the genetic variations representing the 10 loci that were
      significantly linked to SPS, and then used path analysis to search for brain
      regions whose resting-state data would help explain the gene-behavior
      association. Mediation analysis revealed that temporal homogeneity of regional
      spontaneous activity (ReHo) in the precuneus actually suppressed the effect of
      dopamine-related genes on SPS. The path model explained 16% of the variance of
      SPS. This study represents the first attempt at using a multi-gene voxel-based
      neural mediation model to explore the complex relations among genes, brain, and
      personality. 

PMID- 26308207
TI  - Validation of a Mechanistic Model for Non-Invasive Study of Ecological Energetics
      in an Endangered Wading Bird with Counter-Current Heat Exchange in its Legs.
AB  - Mechanistic models provide a powerful, minimally invasive tool for gaining a
      deeper understanding of the ecology of animals across geographic space and time.
      In this paper, we modified and validated the accuracy of the mechanistic model
      Niche Mapper for simulating heat exchanges of animals with counter-current heat
      exchange mechanisms in their legs and animals that wade in water. We then used
      Niche Mapper to explore the effects of wading and counter-current heat exchange
      on the energy expenditures of Whooping Cranes, a long-legged wading bird. We
      validated model accuracy against the energy expenditure of two captive Whooping
      Cranes measured using the doubly-labeled water method and time energy budgets.
      Energy expenditure values modeled by Niche Mapper were similar to values measured
      by the doubly-labeled water method and values estimated from time-energy budgets.
      Future studies will be able to use Niche Mapper as a non-invasive tool to explore
      energy-based limits to the fundamental niche of Whooping Cranes and apply this
      knowledge to management decisions. Basic questions about the importance of
      counter-current exchange and wading to animal physiological tolerances can also
      now be explored with the model. 

PMID- 26308209
TI  - Correction: The Role of Angiotensin II and Cyclic AMP in Alveolar Active Sodium
      Transport.

PMID- 26308210
TI  - Dynamic Digital Channelizer Based on Spectrum Sensing.
AB  - The ability to efficiently channelize a received signal with dynamic sub-channel
      bandwidths is a key requirement of software defined radio (SDR) systems. The
      digital channelizer, which is used to split the received signal into a number of
      sub-channels, plays an important role in SDR systems. In this paper, a design of
      dynamic digital channelizer is presented. The proposed method is novel in that it
      employs a cosine modulated filter bank (CMFB) to divide the received signal into
      multiple frequency sub-bands and a spectrum sensing technique, which is mostly
      used in cognitive radio, is introduced to detect the presence of signal of each
      sub-band. The method of spectrum sensing is carried out based on the eigenvalues
      of covariance matrix of received signal. The ratio of maximum-minimum eigenvalue
      of each sub-band is vulnerable to noise fluctuation. This paper suggests an
      optimized method to calculate the ratio of maximum-minimum eigenvalue. The
      simulation results imply that the design of digital channelizer can effectively
      separate the received signal with dynamically changeable sub-channel signals. 

PMID- 26308208
TI  - Contribution of Mature Hepatocytes to Biliary Regeneration in Rats with Acute and
      Chronic Biliary Injury.
AB  - Whether hepatocytes can convert into biliary epithelial cells (BECs) during
      biliary injury is much debated. To test this concept, we traced the fate of
      genetically labeled [dipeptidyl peptidase IV (DPPIV)-positive] hepatocytes in
      hepatocyte transplantation model following acute hepato-biliary injury induced by
      4,4'-methylene-dianiline (DAPM) and D-galactosamine (DAPM+D-gal) and in DPPIV
      chimeric liver model subjected to acute (DAPM+D-gal) or chronic biliary injury
      caused by DAPM and bile duct ligation (DAPM+BDL). In both models before biliary
      injury, BECs are uniformly DPPIV-deficient and proliferation of DPPIV-deficient
      hepatocytes is restricted by retrorsine. We found that mature hepatocytes
      underwent a stepwise conversion into BECs after biliary injury. In the hepatocyte
      transplantation model, DPPIV-positive hepatocytes entrapped periportally
      proliferated, and formed two-layered plates along portal veins. Within the two
      layered plates, the hepatocytes gradually lost their hepatocytic identity,
      proceeded through an intermediate state, acquired a biliary phenotype, and
      subsequently formed bile ducts along the hilum-to-periphery axis. In DPPIV
      chimeric liver model, periportal hepatocytes expressing hepatocyte nuclear factor
      1beta (HNF-1beta) were exclusively DPPIV-positive and were in continuity to DPPIV
      positives bile ducts. Inhibition of hepatocyte proliferation by additional doses
      of retrorsine in DPPIV-chimeric livers prevented the appearance of DPPIV-positive
      BECs after biliary injury. Moreover, enriched DPPIV-positive BEC/hepatic oval
      cell transplantation produced DPPIV-positive BECs or bile ducts in unexpectedly
      low frequency and in mid-lobular regions. These results together suggest that
      mature hepatocytes but not contaminating BECs/hepatic oval cells are the sources
      of periportal DPPIV-positive BECs. We conclude that mature hepatocytes contribute
      to biliary regeneration in the environment of acute and chronic biliary injury
      through a ductal plate configuration without the need of exogenously genetic or
      epigenetic manipulation. 

PMID- 26308211
TI  - Kidney-Specific Reduction of Oxidative Phosphorylation Genes Derived from
      Spontaneously Hypertensive Rat.
AB  - Mitochondrial (Mt) dysfunction contributes to the pathophysiology of renal
      function and promotes cardiovascular disease such as hypertension. We hypothesize
      that renal Mt-genes derived from female spontaneously hypertensive rats (SHR)
      that exhibit hypertension have reduced expression specific to kidney cortex.
      After breeding a female Okamoto-Aoki SHR (SAP = 188mmHg) with Brown Norway (BN)
      males (SAP = 100 and 104 mmHg), hypertensive female progeny were backcrossed with
      founder BN for 5 consecutive generations in order to maintain the SHR
      mitochondrial genome in offspring that contain over increasing BN nuclear genome.
      Mt-protein coding genes (13 total) and nuclear transcription factors mediating Mt
      gene transcription were evaluated in kidney, heart and liver of normotensive (NT:
      n = 20) vs. hypertensive (HT: n = 20) BN/SHR-mtSHR using quantitative real-time
      PCR. Kidney cortex, but not liver or heart Mt-gene expression was decreased ~2-5
      fold in 12 of 13 protein encoding genes of HT BN/SHR-mtSHR. Kidney cortex but not
      liver mRNA expression of the nuclear transcription factors Tfam, NRF1, NRF2 and
      Pgc1alpha were also decreased in HT BN/SHR-mtSHR. Kidney cortical tissue of HT
      BN/SHR-mtSHR exhibited lower cytochrome oxidase histochemical staining,
      indicating a reduction in renal oxidative phosphorylation but not in liver or
      heart. These results support the hypothesis that renal cortex of rats with SHR
      mitochondrial genome has specifically altered renal expression of genes encoding
      mitochondrial proteins. This kidney-specific coordinated reduction of
      mitochondrial and nuclear oxidative metabolism genes may be associated with
      heritable hypertension in SHR. 

PMID- 26308212
TI  - Spinning-Spot Shadowless TIRF Microscopy.
AB  - Total internal reflection fluorescence (TIRF) microscopy is a powerful tool for
      visualizing near-membrane cellular structures and processes, including imaging of
      local Ca2+ transients with single-channel resolution. TIRF is most commonly
      implemented in epi-fluorescence mode, whereby laser excitation light is
      introduced at a spot near the periphery of the back focal plane of a high
      numerical aperture objective lens. However, this approach results in an irregular
      illumination field, owing to interference fringes and scattering and shadowing by
      cellular structures. We describe a simple system to circumvent these limitations,
      utilizing a pair of galvanometer-driven mirrors to rapidly spin the laser spot in
      a circle at the back focal plane of the objective lens, so that irregularities
      average out during each camera exposure to produce an effectively uniform field.
      Computer control of the mirrors enables precise scanning at 200 Hz (5ms camera
      exposure times) or faster, and the scan radius can be altered on a frame-by-frame
      basis to achieve near-simultaneous imaging in TIRF, widefield and 'skimming
      plane' imaging modes. We demonstrate the utility of the system for dynamic
      recording of local inositol trisphosphate-mediated Ca2+ signals and for imaging
      the redistribution of STIM and Orai proteins during store-operated Ca2+ entry. We
      further anticipate that it will be readily applicable for numerous other near
      membrane studies, especially those involving fast dynamic processes. 

PMID- 26308213
TI  - Layman versus Professional Musician: Who Makes the Better Judge?
AB  - The increasing number of casting shows and talent contests in the media over the
      past years suggests a public interest in rating the quality of vocal
      performances. In many of these formats, laymen alongside music experts act as
      judges. Whereas experts' judgments are considered objective and reliable when it
      comes to evaluating singing voice, little is known about laymen's ability to
      evaluate peers. On the one hand, layman listeners-who by definition did not have
      any formal training or regular musical practice-are known to have internalized
      the musical rules on which singing accuracy is based. On the other hand, layman
      listeners' judgment of their own vocal skills is highly inaccurate. Also, when
      compared with that of music experts, their level of competence in pitch
      perception has proven limited. The present study investigates laypersons' ability
      to objectively evaluate melodies performed by untrained singers. For this
      purpose, laymen listeners were asked to judge sung melodies. The results were
      compared with those of music experts who had performed the same task in a
      previous study. Interestingly, the findings show a high objectivity and
      reliability in layman listeners. Whereas both the laymen's and experts'
      definition of pitch accuracy overlap, differences regarding the musical criteria
      employed in the rating task were evident. The findings suggest that the effect of
      expertise is circumscribed and limited and supports the view that laypersons make
      trustworthy judges when evaluating the pitch accuracy of untrained singers. 

PMID- 26308214
TI  - Self-Assembly of Abeta40, Abeta42 and Abeta43 Peptides in Aqueous Mixtures of
      Fluorinated Alcohols.
AB  - Fluorinated alcohols such as hexafluoroisopropanol (HFIP) and trifluoroethanol
      (TFE) have the ability to promote alpha-helix and beta-hairpin structure in
      proteins and peptides. HFIP has been used extensively to dissolve various
      amyloidogenic proteins and peptides including Abeta, in order to ensure their
      monomeric status. In this paper, we have investigated the self-assembly of
      Abeta40, Abeta42, and Abeta43 in aqueous mixtures of fluorinated alcohols from
      freshly dissolved stock solutions in HFIP. We have observed that formation of
      fibrillar and non-fibrillar structures are dependent on the solvent composition.
      Peptides form fibrils with ease when reconstituted in deionized water from
      freshly dissolved HFIP stocks. In aqueous mixtures of fluorinated alcohols,
      either predominant fibrillar structures or clustered aggregates were observed.
      Aqueous mixtures of 20% HFIP are more favourable for Abeta fibril formation as
      compared to 20% TFE. When Abeta40, Abeta42, and Abeta43 stocks in HFIP are
      diluted in 50% aqueous mixtures in phosphate buffer or deionized water followed
      by slow evaporation of HFIP, Abeta peptides form fibrils in phosphate buffer and
      deionized water. The clustered structures could be off-pathway aggregates.
      Abeta40, Abeta42, and Abeta43 showed significant alpha-helical content in freshly
      dissolved HFIP stocks. The alpha-helical conformational intermediate in Abeta40,
      Abeta42, and Abeta43 could favour the formation of both fibrillar and non
      fibrillar aggregates depending on solvent conditions and rate of alpha-helical to
      beta-sheet transition. 

PMID- 26308215
TI  - Surveillance of Avian H7N9 Virus in Various Environments of Zhejiang Province,
      China before and after Live Poultry Markets Were Closed in 2013-2014.
AB  - BACKGROUND: To date, there have been a total of 637 laboratory-confirmed cases of
      human infection with avian influenza A (H7N9) virus across mainland China, with
      28% (179/637) of these reported in Zhejiang Province. Surveillance of avian H7N9
      virus was conducted to investigate environmental contamination during H7N9
      outbreaks. We sought to evaluate the prevalence of H7N9 in the environment, and
      the effects of poultry market closures on the incidence of human H7N9 cases.
      METHODS: We collected 6740 environmental samples from 751 sampling sites across
      11 cities of Zhejiang Province (China) between January 2013 and March 2014. The
      presence of H7N9 was determined by reverse transcription polymerase chain
      reaction, with prevalence compared between sites and over time. The relationship
      between environmental contamination and human cases of H7N9 infection were
      analyzed using Spearman's ranked correlation coefficient. RESULTS: Of the 6740
      samples, 10.09% (680/6740) were H7N9-positive. The virus was found to circulate
      seasonally, and peaked during the spring and winter of 2013-2014. The prevalence
      of the virus decreased from the north to the southeast of the province,
      coinciding with the geographical distribution of human H7N9 cases. Compared with
      other sampling sites, live poultry markets (LPMs) had the highest prevalence of
      H7N9 virus at 13.94% (667/4784). Of the various sample types analyzed, virus
      prevalence was highest for chopping board swabs at 15.49% (110/710). The
      prevalence of the virus in the environment positively correlated with the
      incidence of human H7N9 cases (r2 = 0.498; P < 0.01). Cities with a higher
      incidence of human H7N9 cases also had a higher prevalence of H7N9 among samples
      and at sampling sites. Following the closure of LPMs at the end of January 2014,
      the prevalence of H7N9 decreased from 19.18% (487/2539) to 6.92% (79/1141). This
      corresponded with a decrease in the number of human H7N9 cases reported.
      CONCLUSIONS: The prevalence of H7N9 virus in environmental samples oscillated
      seasonally, regardless of whether LPMs were open. The presence of H7N9 in
      environmental samples positively correlated with the number of human H7N9 cases,
      indicating that eradication of the virus from the environment is essential in
      reducing the numbers of H7N9 cases and halting the spread of the virus.

PMID- 26308216
TI  - PSCA rs2294008 Polymorphism with Increased Risk of Cancer.
AB  - BACKGROUND: Published data on the association between PSCA rs2294008 polymorphism
      and cancer risk have implicated inconclusive results. To determine the
      relationship and to precisely assess the effect size estimate of the association,
      we performed a meta-analysis. METHODS: We searched published literature in Embase
      and PubMed databases using the search terms "PSCA", "prostate stem cell antigen",
      "variants", "polymorphism", "polymorphisms", and "cancer". A total of 21 eligible
      articles were retrieved, with 27, 197 cancer cases and 48, 237 controls. RESULTS:
      On the whole, we found the association between PSCA rs2294008 polymorphism and
      cancer risk was statistically significant: TT vs CC: OR = 1.18, 95% CI, 1.10 to
      1.27; TT + CT vs CC: OR = 1.08, 95% CI, 1.05 to 1.10; TT vs CT + CC: OR = 1.14,
      95% CI, 1.07 to 1.21; T vs C: OR = 1.10, 95% CI, 1.06 to 1.14; CT vs CC: OR =
      1.10, 95% CI, 1.06 to 1.13. Stratified analyses in cancer type and ethnicity
      showed similar results. CONCLUSIONS: Based on the statistical evidence, we can
      draw a conclusion that the rs2294008 polymorphism of PSCA gene is likely to play
      a role in cancer carcinogenesis, especially in gastric cancer and bladder cancer.

PMID- 26308217
TI  - Protobacco Media Exposure and Youth Susceptibility to Smoking Cigarettes,
      Cigarette Experimentation, and Current Tobacco Use among US Youth.
AB  - PURPOSE: Youth are exposed to many types of protobacco influences, including
      smoking in movies, which has been shown to cause initiation. This study
      investigates associations between different channels of protobacco media and
      susceptibility to smoking cigarettes, cigarette experimentation, and current
      tobacco use among US middle and high school students. METHODS: By using data from
      the 2012 National Youth Tobacco Survey, structural equation modeling was
      performed in 2013. The analyses examined exposure to tobacco use in different
      channels of protobacco media on smoking susceptibility, experimentation, and
      current tobacco use, accounting for perceived peer tobacco use. RESULTS: In 2012,
      27.9% of respondents were never-smokers who reported being susceptible to trying
      cigarette smoking. Cigarette experimentation increased from 6.3% in 6th grade to
      37.1% in 12th grade. Likewise, current tobacco use increased from 5.2% in 6th
      grade to 33.2% in 12th grade. Structural equation modeling supported a model in
      which current tobacco use is associated with exposure to static advertising
      through perception of peer use, and by exposure to tobacco use depicted on TV and
      in movies, both directly and through perception of peer use. Exposure to static
      advertising appears to directly increase smoking susceptibility but indirectly
      (through increased perceptions of peer use) to increase cigarette
      experimentation. Models that explicitly incorporate peer use as a mediator can
      better discern the direct and indirect effects of exposure to static advertising
      on youth tobacco use initiation. CONCLUSIONS: These findings underscore the
      importance of reducing youth exposure to smoking in TV, movies, and static
      advertising.

PMID- 26308218
TI  - Neurocysticercosis in Europe: Need for a One Health Approach.

PMID- 26308219
TI  - Use of Levetiracetam in Neonates in Clinical Practice: A Retrospective Study at a
      German University Hospital.
AB  - OBJECTIVE: We performed a retrospective chart analysis in neonates routinely
      treated with levetiracetam (LEV) in a university setting. Patients and Methods We
      assessed clinical characteristics of the included neonates. Documented LEV doses
      and the duration of treatment were evaluated. To assess LEV effectiveness, we
      compared the need of any additional anticonvulsant as co- and rescue therapies
      before and following the initiation of LEV treatment. To assess LEV tolerance, we
      sought to identify documented adverse drug reactions resulting in a termination
      of LEV treatment. RESULTS: We analyzed a total of 72 neonates receiving LEV with
      a median gestational age at initiation of LEV treatment of 30 (4/7) gestational
      weeks (min., 24(5/7)/max., 43(0/7) weeks). LEV was applied in target doses of
      41.7 mg/kg/d (min., 14.4/max., 106.2 mg/kg/d). Patients received LEV treatment at
      hospital for a median of 28 days (min., 1/max., 195 days). Additional
      anticonvulsant therapy decreased a week after LEV treatment was initiated (p =
      0.008). We did not find any cases of terminated LEV treatment resulting from
      adverse drug reactions. CONCLUSION: Long term use of high LEV doses is rather
      frequent in immature neonates. Our data indicate good effectiveness and a low
      risk of adverse drug reactions.

PMID- 26308221
TI  - Treatment Patterns of Anti-Vascular Endothelial Growth Factor and Laser Therapy
      Among Patients with Diabetic Macular Edema.
AB  - BACKGROUND: Diabetic macular edema (DME) is a form of diabetic retinopathy caused
      by continued leakage from retinal blood vessels. The use of anti-vascular
      endothelial growth factor (VEGF) injections has gained in popularity in the
      treatment of DME due to satisfactory efficacy, while laser photocoagulation is
      still the first-line therapy. Examining anti-VEGF treatment patterns may improve
      understanding of real-world medication-taking behaviors.   OBJECTIVES: To (a)
      compare demographic and clinical characteristics and treatment patterns of anti
      VEGF (bevacizumab, ranibizumab, and pegaptanib) and laser therapies among DME
      patients and (b) determine predictors of switching and anti-VEGF therapy
      initiation.  METHODS: A retrospective cohort analysis was conducted with Texas
      Medicaid medical and prescription claims (January 1, 2008-December 31, 2012) for
      patients who were aged 18-63 years, continuously enrolled 1 year pre- and post
      index, diagnosed with DME and treated with anti-VEGF or laser therapies.
      Treatment patterns included treatment frequency and switching between anti-VEGF
      and laser therapies. Logistic regression and multinomial analysis were used to
      determine factors associated with switching and initiation of anti-VEGF therapy,
      while controlling for demographic and clinical characteristics. RESULTS: DME
      patients (N = 2,201) were aged 54.7 (SD +/- 7.9) years; 63.1% were female; 59.1%
      were Hispanic; and 10.3% were visually impaired. CCI mean score was 6.5 (SD +/-
      3.1), and patients were on 2.6 (SD +/- 3.3) unique prescription medications. Anti
      VEGF users had significantly (P  less than  0.0001) fewer prescriptions compared
      with laser users (1.9 [SD +/- 3.1) vs. 2.8 [SD +/- 3.3], respectively). Laser was
      the most commonly used (84.9%) therapy from 2009 to 2011; however, anti-VEGF use
      increased from 11.7% in 2009 to 21.8% in 2011 (P  less than  0.0001). Patients
      received 1.5 (SD +/- 0.7) laser surgeries compared with 1.7 (SD +/- 1.1) anti
      VEGF injections per eye annually. Switching from laser to anti-VEGF injections
      was 9.7%, while switching from anti-VEGF injections to laser surgery was 42.2%.
      Patients who switched from anti-VEGF injections to laser surgery were more likely
      to be Hispanic (OR = 1.415, 95% CI = 1.037-1.930); male (OR = 1.341, 95% CI =
      1.053-1.709); have fewer prescriptions (OR = 0.944, 95% CI = 0.905-0.985); and
      less likely to have no visual impairment (OR = 0.641, 95% CI = 0.449-0.915).
      Multinomial regression results showed anti-VEGF users were more likely to remain
      on the same therapy if they had more prescriptions (OR = 1.094, 95% CI = 1.029
      1.172) or were female (OR = 1.441, 95% CI = 1.024-2.041). Anti-VEGF initiators
      had fewer prescriptions (OR = 0.917, 95% CI = 0.868-0.947) and initiated in 2011
      vs. 2009 (OR = 2.363, 95% CI = 1.777-3.141).    CONCLUSIONS: Although anti-VEGF
      use is increasing, laser use is still more prevalent. Over 40% of patients who
      initiated on anti-VEGF injections switched to laser surgery. Additional research
      should be conducted to determine factors associated with this high rate of
      switching.

PMID- 26308222
TI  - Association Between Cognitive Function and Health Care Costs 3 Months and 6
      Months After Initiating Antidepressant Medication for Depressive Disorders.
AB  - BACKGROUND: Major depressive disorder is one of the most common and disabling
      mental health disorders and is associated with substantial costs in terms of
      direct health care utilization and workplace productivity. Cognitive dysfunction,
      which alone substantially increases health care costs, is commonly associated
      with major depressive disorder. However, the health care costs of cognitive
      dysfunction in the context of depressive disorder are unknown. Recovery from mood
      symptoms is not always associated with resolution of cognitive dysfunction. Thus,
      cognitive dysfunction may contribute to health care burden even with successful
      antidepressant therapy.  OBJECTIVE: To compare health care utilization and costs
      for patients with a depressive disorder with and without cognitive dysfunction,
      at 3 and 6 months after initiation of antidepressant medication.  METHODS: This
      was an observational study, combining a cross-sectional patient survey,
      administered during a telephone interview, with health care claims data from a
      large, geographically diverse U.S. health plan. Included patients had at least 1
      pharmacy claim for an antidepressant medication between August 1 and September
      30, 2012, and no claim for any antidepressant during the 6 months prior to the
      index date. In addition to other criteria assessed in the claims data, patients
      confirmed a diagnosis of depression or major depressive disorder and the absence
      of any exclusionary neurological diagnoses possibly associated with cognitive
      impairment. Eligible patients were administered validated cognitive function
      assessments of verbal episodic memory (Hopkins Verbal Learning Test-Revised,
      Delayed and Total); attention (Digit Span Forward Maximum Sequence Length);
      working memory (Digit Span Backward Maximum Sequence Length); and executive
      function (D-KEFS-Letter Fluency Test). Based on comparison of scores with
      normative data, patients were assigned to cognitive dysfunction or cognitive
      normal cohorts. All-cause (all diagnoses) and depressive disorder-related health
      care utilization and costs (all from a payer perspective) were assessed 6 months
      prior (baseline) to antidepressant initiation and 3 months and 6 months after
      (follow-up) initiation of antidepressant medication. Health care utilization and
      costs included ambulatory (office and hospital outpatient), emergency room,
      inpatient hospital, pharmacy, other medical (e.g., laboratory and diagnostics),
      and total (all categories combined). All-cause and depressive disorder-related
      total costs during the 3- and 6-month follow-up periods were modeled with
      generalized linear modeling with gamma distribution and log link, while adjusting
      for potential confounders (age, race, gender, education, employment, and
      comorbidities). RESULTS: Of the 13,537 patients who were mailed an invitation,
      824 (6%) were eligible and agreed to participate. Of these, 563 patients provided
      informed consent, completed the interview, maintained eligibility, and were
      included in the 3-month calculations. Among these, 255 (45%) were classified as
      having cognitive dysfunction. Mean patient age was 41.3 (+/- 12.5) years; 80%
      were female. Most patients were white and employed. More patients in the
      cognitive normal cohort were white (P  less than  0.001) and employed full time
      (P = 0.029), had higher education attainment (P  less than    0.001), and had
      fewer comorbidities (P = 0.007) than those in the cognitive dysfunction cohort.
      Over the first 3 months, patients with cognitive dysfunction had higher adjusted
      all-cause costs ($3,309 vs. $2,157, P = 0.002) and higher adjusted depressive
      disorder-related costs ($718 vs. $406, P  less than  0.001) than patients without
      cognitive dysfunction. At 6 months, data from 4 patients were removed from the
      analysis because of exclusionary diagnoses. Over 6 months, patients with
      cognitive dysfunction had higher adjusted all-cause costs ($4,793) than patients
      without cognitive dysfunction ($3,683, P = 0.034). Over 6 months, depressive
      disorder-related costs did not significantly differ between patients with ($771)
      and without cognitive dysfunction ($594, P = 0.071). The main drivers of all
      cause costs were office visits, outpatient hospital visits, and inpatient costs,
      and the main driver of depressive disorder-related costs was inpatient costs.
      CONCLUSIONS: Cognitive dysfunction was associated with higher adjusted all-cause
      and depressive disorder-related costs 3 months after initiation of an
      antidepressant medication. This difference persisted for all-cause costs through
      6 months. Identification and treatment of cognitive dysfunction in patients with
      depressive disorder might reduce health care costs.

PMID- 26308223
TI  - Antipsychotic Adherence and Rehospitalization in Schizophrenia Patients Receiving
      Oral Versus Long-Acting Injectable Antipsychotics Following Hospital Discharge.
AB  - BACKGROUND: Antipsychotic medications are a central component of effective
      treatment for schizophrenia, but nonadherence is a significant problem for the
      majority of patients. Long-acting injectable (LAI) antipsychotic medications are
      a recommended treatment option for nonadherent patients, but evidence regarding
      their potential advantages has been mixed. Observational data on newer, second
      generation LAI antipsychotic medications have been limited given their more
      recent regulatory approval and availability. OBJECTIVE: To examine antipsychotic
      medication nonadherence, discontinuation, and rehospitalization outcomes in
      Medicaid patients receiving oral versus LAI antipsychotic medications in the 6
      months after a schizophrenia-related hospitalization. METHODS: The 2010-2013
      Truven Health Analytics MarketScan Medicaid research claims database was used to
      identify adult patients with a recent history of nonadherence (prior 6 months)
      who received an oral or LAI antipsychotic medication within 30 days after an
      index schizophrenia-related hospitalization. Primary outcome measures were
      nonadherence (proportion of days covered less than  0.80), discontinuation
      (continuous medication gap >= 60 days), and schizophrenia-related
      rehospitalization, all in the 6 months after discharge. Descriptive analyses
      compared users of oral versus LAI antipsychotic medication on sociodemographic,
      clinical, and treatment characteristics. Logistic regressions were used to
      examine associations between use of oral versus LAI antipsychotics and each study
      outcome while controlling for observed differences in sample characteristics. All
      outcomes were compared at 3 levels of analysis: overall LAI class, LAI
      antipsychotic generation (first-generation [FGA] or second-generation [SGA]
      antipsychotics), and individual LAI agent (fluphenazine decanoate, haloperidol
      decanoate, risperidone LAI, and paliperidone palmitate). RESULTS: Of the final
      sample, 91% (n = 3,428) received oral antipsychotics, and 9.0% (n = 340) received
      LAI antipsychotics after discharge. Slightly over half (n =183, 53.8%) of LAI
      users used an SGA LAI. A smaller percentage of patients receiving LAIs were
      nonadherent (51.8% vs. 67.7%, P  less than  0.001); had a 60-day continuous gap
      in medication (23.8% vs. 39.4%, P  less than  0.001); and were rehospitalized for
      schizophrenia (19.1% vs. 25.3%, P = 0.01) compared with patients receiving oral
      medications. The size of these differences was magnified when comparing SGA LAI
      users with users of oral antipsychotics for nonadherence. After controlling for
      all differences in measured covariates, LAI initiators had lower odds of being
      nonadherent (adjusted odds ratio [AOR] = 0.35, 95% CI = 0.27-0.46, P  less than 
      0.001) and of having continuous 60-day gaps (AOR = 0.45, 95% CI = 0.34-0.60, P 
      less than  0.001) when compared with patients receiving oral medications. Both
      FGA and SGA LAI users had lower odds of nonadherence compared with patients
      receiving oral antipsychotics. Similarly, FGA LAI users (AOR = 0.58, 95% CI =
      0.40-0.85, P = 0.005) and SGA LAI initiators (AOR = 0.34, 95% CI =0.23-0.51, P 
      less than  0.001) had lower odds of a 60-day continuous gap compared with
      patients receiving oral antipsychotics. Compared with those receiving oral
      antipsychotics, LAI initiators also had lower odds of rehospitalization (AOR =
      0.73, 95% CI = 0.54-0.99, P = 0.041); however, when examined separately, only
      patients receiving SGA LAIs (AOR = 0.59, 95% CI = 0.38-0.90, P = 0.015) and not
      FGA LAIs (AOR = 0.90, 95% CI = 0.60-1.34, P = 0.599) had a statistically
      significant reduction in odds of rehospitalization. Among individual LAIs, odds
      of rehospitalization only among initiators of paliperidone palmitate were
      statistically different from those among users of oral antipsychotics (AOR =
      0.53, 95% CI = 0.30-0.94, P = 0.031). While odds of rehospitalization were 33%
      lower among patients receiving risperidone LAI compared with those receiving oral
      antipsychotics, the estimate did not reach statistical significance (AOR = 0.67,
      95% CI = 0.37-1.22, P = 0.194).  CONCLUSIONS: This claims-based analysis of
      posthospitalization adherence and rehospitalization outcomes in Medicaid patients
      with schizophrenia adds to the growing real-world evidence base of the benefits
      of LAI antipsychotic medications in routine clinical practice, particularly with
      regard to second-generation LAIs. As new SGA formulations become available for
      long-acting use, real-world studies with larger sample sizes will be needed to
      further delineate their potential advantages in terms of clinical outcomes and
      costs.

PMID- 26308224
TI  - Measurement of Metabolic Monitoring in Youth and Adult Medicaid Recipients
      Prescribed Antipsychotics.
AB  - BACKGROUND: Individuals being treated with first- and second-generation
      antipsychotics (FGAs and SGAs) are at risk for a variety of adverse
      cardiometabolic effects. Although consensus guidelines that recommend metabolic
      monitoring for patients receiving SGAs have been in place since 2004, the rate of
      monitoring remains low, especially in the pediatric population. OBJECTIVES: To
      (a) examine differences in rates of laboratory monitoring for glucose and lipids
      for adults and youth prescribed FGAs and SGAs; (b) look at factors associated
      with the likelihood of metabolic testing; and (c) describe cohort effects that
      may have had an impact on the rates of laboratory testing.  METHODS: This is a
      retrospective study examining the rates of glucose and lipid testing for 3
      separate cohorts of Medicaid recipients who were prescribed antipsychotics during
      3 measurement periods-2008, 2010, and 2012-using paid Medicaid pharmacy and
      laboratory claims data. The sample included adults aged 18 years and older and
      children aged 17 years and younger. For each measurement period, we identified
      the rate of metabolic monitoring and the demographic characteristics for each
      individual, including race, age, and gender. The proportion of laboratory
      monitoring was assessed using chi square tests for each of the outcomes. Logistic
      regression models for each time point were used to determine the characteristics
      of individuals who were more likely to receive monitoring. RESULTS: The
      proportion of individuals receiving glucose and lipid tests increased for both
      age groups across all measurement periods. For individuals aged 18 years and
      over, glucose monitoring increased from 56.6%-72.6%. Testing for lipids remained
      constant, ranging from 38.3%-41.2% for each of the 3 measurement periods. During
      the first measurement period, in 2008, females were 41% and 15% more likely to
      receive glucose and lipid laboratory monitoring, respectively, compared with
      males. Females continued to be more likely to receive glucose monitoring during
      the measurement periods in 2010 and 2012, although there was no significant
      difference between females and males for lipid monitoring during these time
      periods. Individuals aged 17 years and younger were 59%-68% less likely to
      receive glucose monitoring than adults (aged >= 18 years) for all time points.
      Across all measurement periods, individuals aged <= 17 years were also 44%-58%
      less likely to receive lipid monitoring compared with adults (aged >= 18 years).
      While there was no significant difference between Caucasians and non-Caucasians
      in the first measurement period, Caucasians were about 30% less likely to receive
      glucose monitoring and about 50% less likely to receive lipid monitoring during
      the measurement periods covering 2010 and 2012.   CONCLUSIONS: Metabolic
      monitoring in adults improved substantially over the time periods studied;
      however, rates remained suboptimal, especially in the pediatric population. This
      finding suggests that interventions to increase metabolic monitoring in adults
      and children using FGAs and SGAs are necessary.

PMID- 26308225
TI  - Health Care Utilization and Treatment Persistence Associated with Oral
      Paliperidone and Lurasidone in Schizophrenia Treatment.
AB  - BACKGROUND: Oral paliperidone and lurasidone are new second-generation
      antipsychotics (SGAs). Empirical evidence on the comparative costs and
      persistence of these 2 agents are absent in the literature. OBJECTIVE: To assess
      health care use and persistence associated with the 2 new agents oral
      paliperidone and lurasidone and other SGAs. METHODS: Schizophrenia patients who
      initiated SGA therapy were identified in the January 2007-June 2013 claims
      databases of a large managed care organization. Multivariate regressions using
      aripiprazole as the comparator were conducted. Ordinary least squares regressions
      were used to estimate the total medical and pharmacy costs associated with each
      drug. Poisson regressions were conducted to evaluate the frequency of
      hospitalizations and emergency department (ED) visits associated with each drug.
      A censored regression model was used to evaluate the comparative persistence.
      Sensitivity analyses using generalized linear models, two-part models, hurdle
      models, and instrumental variable regressions were also performed.   RESULTS:
      Compared with aripiprazole, paliperidone was not associated with significantly
      different total costs, yet lurasidone was associated with lower total costs (
      $7,052; 95% CI = -$9,221, -$4,882). Lurasidone was also associated with
      significantly lower medical services costs (-$5,025; 95% CI = -$7,096, -$2,955),
      drug costs (-$2,026; 95% CI = -$2,695, -$1,357), hospital costs (-$3,026; 95% CI
      = -$4,731, -$1,321), outpatient costs (-$1,999; 95% CI = -$2,536, -$1,463), and
      ED costs (-$2,284; 95% CI = -$3,069, -$1,499), whereas paliperidone did not have
      significant effects on any types of costs. Paliperidone users had fewer ED visits
      (-0.25; 95% CI = -0.42, -0.08), while lurasidone users had fewer hospitalizations
      (-5.98; 95% CI = -6.61, -5.35) and fewer ED visits (-2.51; 95% CI = -2.92, 
      2.10). Both paliperidone and lurasidone were associated with lower levels of
      treatment persistence. CONCLUSIONS: Paliperidone does not associate with lower
      total costs compared with commonly used SGAs, whereas lurasidone is associated
      with lower total health costs. Thus, high access fees of lurasidone are not
      necessarily a major concern in prescription.

PMID- 26308226
TI  - Impact of a Step Therapy for Guanfacine Extended-Release on Medication
      Utilization and Health Care Expenditures Among Individuals Receiving Treatment
      for ADHD.
AB  - BACKGROUND: While step therapy (ST) policies are generally effective at reducing
      cost through the managed utilization of targeted medications, the clinical
      implications of ST policies are not clear and may vary across therapeutic areas.
      Guanfacine extended-release (GXR) is approved by the FDA for the treatment of
      attention-deficit/hyperactivity disorder (ADHD) as both monotherapy and
      adjunctive to stimulant treatment. At the introduction of GXR to the market,
      Humana implemented an ST policy on GXR requiring the documentation of previous
      treatment, intolerance, or contraindication to generic clonidine or guanfacine.
      OBJECTIVE: To examine the impact of a GXR ST coverage determination (i.e.,
      approved vs. denied) on medication utilization and health care costs among
      members of a commercial health plan with an ST policy for GXR.  METHODS: This
      study was a retrospective cohort study of administrative claims data. Humana
      commercial members prescribed GXR who had an ST coverage determination review
      were identified. All members included in this analysis were required to be aged 6
      17 years, have a diagnosis of ADHD or be receiving stimulant medication, have an
      ST coverage determination (index event) between September 1, 2009, and May 30,
      2012, and have 6 months of pre- and post-index continuous enrollment. Members
      were assigned to either the approved or denied group based on the outcome of the
      ST coverage determination. Medical and pharmacy claims data were used to measure
      baseline demographic and clinical characteristics and to measure medication
      utilization and health care costs. Outcomes assessed during follow-up included
      ADHD medication use, proportion of days covered (PDC) with any ADHD medication
      treatment, time to first observed post-index ADHD treatment, and all-cause and
      mental health (MH)-related health care costs. Administrative costs associated
      with the coverage determination process were also estimated. Bivariate and
      multivariable adjusted analyses were conducted to compare medication utilization
      and health care costs between the approved and denied groups. RESULTS: A total of
      642 members were included in the analysis (denied group n = 395 [61.5%], approved
      group n = 247 [38.5%]). The approved and denied groups were similar in terms of
      baseline demographics, provider characteristics, and baseline MH diagnoses, with
      the exception of anxiety disorders being more prevalent in the approved group
      compared with the denied group (18.2% vs. 10.6%, P = 0.006). A denied GXR
      coverage determination was associated with a greater percentage of members
      receiving no ADHD treatment post-index (13.9% vs. 3.2%, P  less than  0.001),
      greater mean [SD] number of days between index and first observed post-index ADHD
      medication claim (44.5 [59.6] vs. 17.6 [33.4], P  less than  0.001), and lower
      mean [SD] PDC with any ADHD medication post-index (0.59 [0.33] vs. 0.75 [0.26], P
      less than  0.001). These findings remained statistically significant in
      multivariable regression models. Unadjusted pre-index median total health care
      costs and MH-related costs were greater among the approved group compared with
      the denied group (total health care: $1,582 vs. $1,465, P = 0.033; MH-related:
      $993 vs. $981, P = 0.020). Likewise, post-index median total health care and MH
      related costs were greater among the approved group compared with the denied
      group (total: $2,056 vs. $1,420, P  less than  0.001; MH-related: $1,543 vs.
      $946, P  less than  0.001). After adjustment for potentially confounding
      covariates including pre-index costs, there were no statistically significant
      differences between the approved and denied groups in all-cause total health care
      (P = 0.393) or MH-related health care costs (P = 0.054).  CONCLUSIONS: The
      current study found that GXR coverage denial was associated with lower rate of
      ADHD medication utilization, greater delay in receiving ADHD medication, and
      lower PDC with ADHD medication. There were no differences observed between the
      approved and denied group in terms of all-cause total health care or MH-related
      total health care costs after controlling for potentially confounding variables.
      Prior to implementation in the ADHD therapeutic area and others, payers should
      consider the potentially unintended consequences of ST policies, including delay
      in treatment and undertreatment.

PMID- 26308227
TI  - Evaluation of a Nationwide Pharmacist-Led Phone Outreach Program to Improve
      Osteoporosis Management in Older Women with Recently Sustained Fractures.
AB  - BACKGROUND: Osteoporosis-related fractures are a considerable economic burden on
      the U.S. health care system. Since 2008, the Centers for Medicare Medicaid
      Services have adopted a Medicare Part C Five-Star Quality Rating measure to
      ensure that a woman's previously unaddressed osteoporosis is managed
      appropriately after a fracture. Despite the effort to improve this gap in care,
      the 2013 CMS plan ratings fact sheet reported an average star rating of 1.4 stars
      for the osteoporosis measure, the lowest score for any measure across all health
      plans. OBJECTIVE: To evaluate the impact of conducting a pharmacist-led,
      telephone outreach program to members or their providers to improve osteoporosis
      management in elderly women after experiencing fractures.  METHODS: This was a
      prospective, randomized study to evaluate the effectiveness of 3 different
      intervention strategies within a nationwide managed care population. Women aged
      66 years and older who experienced a new bone fracture between January 1, 2012
      August 31, 2012, were identified through medical claims. Women who were treated
      with an osteoporosis medication or received a bone mineral density (BMD) test
      within a year of their fractures were excluded. Study patients were randomized
      into 3 intervention cohorts: (1) baseline intervention consisting of member
      educational mailing and provider educational mail or fax notification; (2)
      baseline intervention plus a live outbound intervention call to members by a
      pharmacist; and (3) baseline intervention plus a pharmacist call to members'
      providers to recommend starting osteoporosis therapy and/or a bone mineral
      density (BMD) test. An intent-to-treat and per protocol analyses were employed,
      and appropriate osteoporosis management (initiation of osteoporosis therapy
      and/or BMD testing) 120 days after the baseline intervention and 180 days after a
      fracture were measured. RESULTS: The study identified 6,591 members who were
      equally randomized into 3 cohorts. The baseline demographics in each cohort were
      similar. Results of the intent-to-treat analysis showed more members in cohort 3
      receiving appropriate osteoporosis management (13.0%) compared with those in
      cohort 2 (10.3%, P  less than  0.005) or compared with those in cohort 1 (9.1%, P
      less than  0.001). No difference was detected between those receiving additional
      member calls (cohort 2) and those receiving only the baseline intervention
      (cohort 1). Similar results were observed utilizing the 180 days after fracture
      time frame.  CONCLUSIONS: The effectiveness of a pharmacist-led telephone
      intervention directed at providers or members was examined in this randomized
      study. Pharmacist calls to members did not improve osteoporosis management over
      member and provider mail and fax notifications. Greater impact was demonstrated
      by performing a pharmacist call intervention with providers rather than with
      members.

PMID- 26308228
TI  - Association Between Gastrointestinal Events and Health Care Resource Utilization
      Among Patients with Osteoporosis: Analysis of a U.S. Managed Care Population.
AB  - BACKGROUND: Among patients on osteoporosis therapy, including oral
      bisphosphonates (BIS), upper gastrointestinal (GI) conditions have been linked
      with lower adherence to treatment and increased treatment discontinuation in
      clinical practice. Patients who are nonadherent to treatment have a higher risk
      of osteoporotic fractures and, consequently, have greater use of health care
      services. The burden of upper gastrointestinal events on health care resource
      utilization (HCRU) among women initiating oral BIS has not been well
      investigated. OBJECTIVE: To examine the association of upper GI events and HCRU
      in women initiating oral BIS.  METHODS: Using a U.S. national claims database,
      this retrospective study identified women aged >= 55 years who were prescribed
      oral BIS during 2001-2011 and had no history of GI events 12 months prior to
      treatment initiation. Patients with medical claims for an upper GI event <= 4
      months posttreatment initiation were cases; all others were controls. The date of
      the first upper GI event among cases and a randomly assigned date <= 4 months
      posttreatment initiation among controls was the index date. Cases were matched
      1:1 to controls by propensity scores derived from logistic regression of pre
      index patient characteristics. Outcomes were all-cause and osteoporosis (OP)
      related HCRU in the 6-month post-index period. Differences were assessed using
      McNemar's test. RESULTS: Of the 62,863 eligible patients, 4,751 (7.6%)
      experienced an upper GI event <= 4 months posttreatment initiation (cases); 4,739
      cases were matched with 4,739 controls. Compared with controls, cases had higher
      rates of all-cause HCRU (outpatient: 99.3% vs. 87.8%; inpatient: 20.2% vs. 6.4%;
      emergency room [ER]: 12.5% vs. 7.4%; all P  less than  0.0001) and OP-related
      HCRU (outpatient: 24.6% vs. 18.2%; inpatient: 3.4% vs. 1.0%; ER: 0.7% vs. 0.4%;
      all P  less than  0.05). CONCLUSIONS: Patients with upper GI events had higher
      rates of all-cause and OP-related health care utilization. Upper GI events may
      pose an incremental HCRU burden among patients initiating BIS.

PMID- 26308229
TI  - Persistance and Compliance with Osteroporosis Therapies Among Women in a
      Commercially Insured Population in the United States.
AB  - BACKGROUND: Prior research has shown that rates of persistence and compliance
      with osteoporosis therapies are associated with significantly fewer vertebral,
      nonvertebral, and hip fractures. A number of studies have examined medication
      taking behavior with oral bisphosphonates and teriparatide, and these 1-year
      persistence rates have ranged from 39.9% to 56.7%. Limited real-world data are
      available regarding persistence and compliance rates with newer therapies such as
      denosumab, a RANK ligand inhibitor administered every 6 months as a subcutaneous
      injection.  OBJECTIVE: To assess persistence and compliance rates over 1 year
      with newly initiated osteoporosis therapies, including denosumab, alendronate,
      ibandronate, risedronate, raloxifene, and teriparatide, within a cohort of
      commercially insured women.  METHODS: Health insurance claims data derived from
      Truven Health Analytics MarketScan Commercial Claims and Encounters and Medicare
      Supplemental and Coordination of Benefits databases (2010-2013) were used to
      conduct this retrospective cohort study. Adult females aged 18 years and older
      newly initiated on denosumab, raloxifene, teriparatide, or oral bisphosphonates
      (alendronate, ibandronate, or risedronate) between January 1, 2012, and March 31,
      2012, were identified for inclusion. The date of the first qualifying
      osteoporosis prescription claim was defined as the index date. Patients were
      required to have at least 24 months of pre-index and at least 12 months of post
      index continuous enrollment with medical and pharmacy benefits. Outcomes of
      patients initiating zoledronic acid (administered intravenously once yearly) were
      not assessed because a 12-month follow-up period would be insufficient for
      tracking persistence and compliance for this medication. Patients with Paget's
      disease of the bone, osteogenesis imperfecta, hypercalcemia, malignant cancer and
      metastasis, human immunodeficiency virus, and patients receiving preventive
      treatment for risk of breast cancer or denosumab in the pre-index period were
      excluded from the study. A subcohort of women aged 50 years and older at high
      risk for fracture (indicated by 1 or more of the following: aged >= 70 years, a
      pre-index fracture, or pre-index use of osteoporosis therapy that was
      discontinued at least 3 months prior to index) was analyzed separately.
      Propensity score weighting was used to adjust for differences in baseline
      demographic and clinical characteristics. Persistence, indicated by continuous
      use of the index therapy without a gap of 60 days or more; medication coverage
      ratio (MCR), the proportion of days covered by the index therapy; and compliance,
      defined as an MCR >= 0.80, were assessed during the 12-month follow-up. Logistic
      regression was used to estimate the odds of persistence and compliance for the
      treatment groups of interest. RESULTS: 10,863 female patients newly initiating
      osteoporosis medications (mean [SD] age: 66.2 [11.5] years) were identified. In
      the pre-index period, 35.8% of patients had a diagnosis of osteoporosis, while
      11.5% had a diagnosis of osteopenia. Pre-index osteoporosis treatment was
      identified in 29.1% of patients, and 13.6% had an osteoporosis-related fracture
      in the pre-index period. Propensity score weight-adjusted 12-month persistence
      with the index medication varied from 28.9% to 35.1% for oral bisphosphonate
      users, 42.0% for raloxifene users, 59.1% for teriparatide users, and 68.3% for
      denosumab users (P  less than  0.0001). The adjusted mean [SD] MCR was highest
      among patients treated with denosumab (0.83 [0.21]), followed by teriparatide
      (0.67 [0.31]), raloxifene, (0.57 [0.34]), ibandronate (0.54 [0.32]), alendronate
      (0.51 [0.33]), and risedronate (0.46 [0.33]; P  less than  0.0001). The odds of
      being persistent and compliant across treatments favored denosumab (OR = 1.59 to
      5.56, P  less than  0.05 for persistence; OR =  2.44 to 7.69, P  less than 
      0.0001 for compliance). Results were similar in the subcohort of women aged 50
      years and older at high risk for fracture (n = 6,187; mean [SD] age: 71.9 [10.9]
      years). The odds of being persistent and compliant across treatments also favored
      denosumab (OR = 1.62 to 5.75, P  less than  0.0001 for persistence; OR = 2.36 to
      7.25, P  less than  0.0001 for compliance). CONCLUSIONS: In a U.S. setting, rates
      of persistence and compliance over 12 months were higher among women initiating
      denosumab compared with those initiating other osteoporosis therapies.

PMID- 26308230
TI  - Cost-Effectiveness of Pazopanib Versus Sunitinib for Renal Cancer in the United
      States.
AB  - We write to comment on a recently published study by Delea et al. in the January
      2015 issue of JMCP that evaluated the cost-effectiveness (CE) of sunitinib (SU)
      versus pazopanib (PAZ) as first-line treatment for metastatic renal cell
      carcinoma (mRCC) from a U.S. third-party payer perspective.1 This analysis was
      based on COMPARZ and PISCES, clinical trials that compared SU and PAZ2,3 and led
      the authors to conclude that PAZ is cost-effective (in fact, dominant, according
      to the base-case results) compared with SU. Such assessment of economic value is
      clearly important for deciding between therapies to ensure fair access;
      therefore, we welcome a comparative evaluation of SU and PAZ. However, we believe
      that some of the key assumptions and inputs used in the model by Delea et al.
      render their results and conclusions invalid.  Best practice requires that
      results from a health economic model should reflect the most likely outcomes
      based on sound methodology and robust evidence for its inputs, as recommended by
      the International Society of Pharmacoeconomics and Outcomes Research (ISPOR).4
      Here, we focus on 2 key areas (utilities and survival modeling) where, in our
      view, the analysis by Delea et al. falls short of this standard, and a third area
      (treatment costs) where the basis for the data derived is unclear. 

PMID- 26308231
TI  - Health Care Costs Among Renal Cancer Patients Using Pazopanib and Sunitinib.
AB  - Publications that aim to assess the economics of different therapies are
      important because they complement clinical trial data and may aid in decision
      making. We therefore read with interest the study by Hansen et al. in the January
      2015 issue of JMCP. This study compared  costs between pazopanib (PAZ) and
      sunitinib (SU) in the first-line treatment of patients with metastatic renal cell
      carcinoma (mRCC).1 The authors assessed health care costs through assignment of
      costs from the Truven Health MarketScan Databases to the self-reported health
      care resource utilization (HCRU) data from the population studied in the phase
      III noninferiority clinical trial COMPARZ (Pazopanib versus sunitinib in
      metastatic renal cell carcinoma).2 We are writing to comment on the conclusions
      drawn from the results presented, the methodology used, and to request additional
      information and clarification on data presented. 

PMID- 26308232
TI  - Hormone therapy for ovarian cancer survivors: systematic review and meta
      analysis.
AB  - OBJECTIVE: Hormone therapy (HT) alleviates menopausal symptoms, but there is a
      lack of consensus regarding its use among premenopausal ovarian cancer survivors.
      METHODS: We systematically reviewed the literature and searched the Medline (1966
      2014), Scopus (2004-2014), Popline (1974-2014), ClinicalTrials.gov (2008-2014),
      and Cochrane Central Register of Controlled Trials CENTRAL (1999-2014) databases
      and the reference lists of electronically retrieved studies. Statistical meta
      analysis was performed using RevMan 5.1 software. RESULTS: Six studies were
      included in our systematic review, which involved 1,521 women. Among them, 451
      women (29.6%) received HT, whereas the remaining 1,070 women (70.4%) did not
      receive any treatment. We noticed a statistically significant reduction of
      ovarian cancer-related deaths among women who received HT (odds ratio, 0.47; 95%
      CI, 0.28-0.80); however, disease recurrence rates did not differ between the two
      groups (odds ratio, 0.71; 95% CI, 0.45-1.14). Studies included in the present
      systematic review did not report a significant difference in overall survival and
      disease-free survival rates among women receiving HT and controls. CONCLUSIONS:
      Based on the results of meta-analysis, HT does not influence the odds of ovarian
      cancer recurrence; however, this conclusion must be confirmed separately because
      of significant limitations in the methodological quality of the studies included.

PMID- 26308233
TI  - Impact of aromatase inhibitor treatment on vertebral morphology and bone mineral
      density in postmenopausal women with breast cancer.
AB  - OBJECTIVE: The aim of this study was to evaluate the impact of aromatase
      inhibitor (AI) treatment on vertebral morphology by vertebral fracture assessment
      in postmenopausal women with early-stage breast cancer. METHODS: A clinical cross
      sectional study was conducted. A group of 156 postmenopausal women with breast
      cancer (mean [SD] age, 60.4 [10.1] y; mean [SD] time since menopause, 11.7 [9.2]
      y) was included in the study. Eighty-two women received AI treatment, whereas 74
      women did not. Women underwent extensive medical history check and risk factor
      assessment together with vertebral morphology and bone mineral density (BMD)
      evaluation. RESULTS: In the studied population, the prevalence of vertebral
      fractures identified by vertebral fracture assessment was 16.6%. Multivariate
      analysis showed that AI treatment was significantly associated with vertebral
      fractures (adjusted P < 0.04). Women receiving AI treatment had a higher
      prevalence of vertebral fractures than women not treated with AIs (25.6% vs. 4%).
      The risk of vertebral fractures in women treated with AIs was significantly
      higher than in non-AI-treated women (adjusted odds ratio, 4.7; P < 0.005).
      Vertebral fractures of the highest grade were identified at the lumbar spine.
      Women treated with AIs had a significantly lower BMD than women not treated with
      AIs (P < 0.01). Reduction of BMD was significantly associated with length of
      therapy, whereas there was no association between length of treatment and risk of
      vertebral fractures. CONCLUSIONS: AI treatment severely impacts vertebral
      morphology. Our study demonstrates a high prevalence of asymptomatic vertebral
      fractures in women treated with AIs.

PMID- 26308234
TI  - Carotid artery distensibility and hormone therapy and menopause: the Los Angeles
      Atherosclerosis Study.
AB  - OBJECTIVE: Observational studies have suggested that arterial distensibility
      decreases during menopause; however, its relationship with hormone therapy use
      remains controversial. We prospectively studied distensibility and hormone
      therapy use at different menopause stages. METHODS: One hundred sixty-one women
      (aged between 42 and 61 y) without cardiovascular disease underwent carotid
      artery measurements by ultrasound to calculate distensibility index at baseline
      and 3 years later. Menopause stage was classified at each visit as premenopausal,
      perimenopausal, and postmenopausal. Across 3 years of prospective observation,
      women were classified as remaining premenopausal, remaining postmenopausal, or
      transitioning (defined as change from premenopausal to perimenopausal, from
      premenopausal to postmenopausal, from perimenopausal to perimenopausal, or from
      perimenopausal to postmenopausal). RESULTS: Distensibility declined across time
      at all menopause stages (P < 0.0001). Compared with postmenopausal women,
      premenopausal and transitioning/no hormone therapy women had more than twice the
      decline in distensibility index (P = 0.06 and P = 0.016, respectively), whereas
      transitioning/hormone therapy women did not differ in distensibility decline (P =
      0.28). In a multivariate model, change in systolic blood pressure (P < 0.0001)
      and change in pulse pressure (P = 0.004) were independent predictors of
      distensibility index change and served as effect modulators. In an adjusted
      model, women in the premenopausal and transitioning/no hormone therapy groups had
      a significantly faster decline in distensibility index (P = 0.002 and P = 0.001,
      respectively) compared with postmenopausal women, whereas the
      transitioning/hormone therapy group did not (P = 0.21). CONCLUSIONS: These
      findings confirm that the menopausal transition is associated with reduced
      vascular compliance. Hormone therapy is associated with better arterial
      distensibility only during the menopausal transition. Additional prospective
      studies are needed to confirm these findings and to determine whether hormone
      therapy use beyond the menopausal transition is related to distensibility.

PMID- 26308236
TI  - Global minimization of gold clusters by combining neural network potentials and
      the basin-hopping method.
AB  - Neural network potentials trained by first-principles density functional theory
      total energies were applied to search for global minima of gold nanoclusters
      within the basin-hopping method. Using Au58 as an example, we found a new
      putative global minimum which has a core-shell structure of Au10@Au48 and C4
      symmetry. This new structure of Au58 is 0.24 eV per formula more stable than the
      best previous model that has C1 symmetry. This work demonstrates that neural
      network potentials combined with the basin-hopping method could be very useful in
      global minimization for medium-sized metal clusters which might be
      computationally prohibitive for first principles density functional theory. 

PMID- 26308235
TI  - Conformational variability of recombination R-triplex formed by the mammalian
      telomeric sequence.
AB  - Alignment of three nucleic acids strands, in which the third strand is identical
      to one of the DNA duplex strands, occurs in various cellular systems. In the case
      of telomeric t-loops, recognition between the DNA duplex and the homologous
      single strand is likely to be mediated by proteins through formation of the
      transient recombination-type R-triplex. Earlier, using 2-aminopurine as a
      fluorescent reporting base, we evaluated the thermodynamic characteristics of
      intramolecular R-triplex formed by a mixed nucleotide sequence. Here, we used
      this approach to explore a propensity of the telomeric TTAGGG repeat to form the
      R-triplex. The circular dichroism spectral changes detected upon formation of the
      R-triplex suggest that this process is accompanied by specific conformational
      changes in DNA, including a local destabilization of the target duplex next to a
      GGG run revealed by the fluorescence of the reporting 2-aminopurine base.
      Surprisingly, stability of the R-triplex formed by telomeric sequence depends
      strikingly on the counter ion, being higher for Na(+) than for Li(+). Taken
      together these findings indicate a significant conformational variability of
      telomeric DNA in the context of recombination-type R-triplex, a phenomenon of
      possible biological relevance. 

PMID- 26308238
TI  - Circulating MicroRNA and Long Noncoding RNA as Biomarkers of Cardiovascular
      Diseases.
AB  - Although >85% of the human genome is transcribed, only <2% is transcribed into
      protein-coding RNA (messenger RNA, mRNA). Many thousands of noncoding RNAs are
      transcribed and recognized as functional RNAs with diverse sizes, structures, and
      biological functions. Based on size, noncoding RNA can be generally divided into
      two subgroups: short noncoding RNA (<200 nucleotides including microRNA or miRNA)
      and long noncoding RNA (lncRNA, >200 nucleotides). It is now clear that these
      RNAs fulfil critical roles as transcriptional and post-transcriptional regulators
      and as guides of chromatin-modifying complexes. Although not translated into
      protein, noncoding RNAs can regulate cardiac function through diverse mechanisms
      and their dysregulation is increasingly linked with cardiovascular
      pathophysiology. Furthermore, a series of recent studies have discovered that
      noncoding RNAs can be found in the bloodstream and some species are remarkably
      stable. This has raised the possibility that such noncoding RNAs may be measured
      in body fluids and serve as novel diagnostic biomarkers. Here, we summarize the
      current knowledge of noncoding RNAs' function and biomarker potential in cardiac
      diseases, concentrating mainly on circulating miRNAs and lncRNAs. J. Cell.
      Physiol. 231: 751-755, 2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 26308239
TI  - Infants' unprovoked acts of force toward others.
AB  - Infants harm others at higher rates than older children and adults. A common
      explanation is that infants fail to regulate their frustration, becoming
      aggressive when they do not get what they want. The present research investigated
      whether infants also use force against others without provocation, for instance
      because they seek to explore the consequences of hitting or try to pet someone
      using too much force. Two studies with infants aged 11 to 24 months investigated
      infants' use of force against others in everyday life using maternal report
      (Study 1) and direct observation (Study 2). In both studies, a large proportion
      of infants' acts of force were unprovoked and occurred without signs of infant
      distress. Unlike provoked acts, unprovoked acts showed a decrease late in the
      second year and were positively associated with reports of infant pleasure
      proneness. The presence of unprovoked acts of harm may reflect that infants'
      actions are not reliably guided by an aversion for harming others and may provide
      unique opportunities for early moral development.

PMID- 26308240
TI  - Spleen Tyrosine Kinase Modulates Fibrous Airway Obliteration and Associated
      Lymphoid Neogenesis After Transplantation.
AB  - Chronic lung allograft dysfunction, the major cause of death following lung
      transplantation, usually manifests as irreversible airflow obstruction associated
      with obliterative bronchiolitis (OB), a lesion characterized by chronic
      inflammation, lymphoid neogenesis, fibroproliferation and small airway
      obliteration. Spleen tyrosine kinase (Syk), a tyrosine kinase that regulates B
      cell function and innate immunity, has been implicated in the pathogenesis of
      chronic inflammation and tissue repair. This study evaluated the role of Syk in
      development of OB, using an intrapulmonary tracheal transplant model of OB with
      the conditional Syk-knockout Syk(flox/flox) //rosa26-CreER(T2) mice and a Syk
      selective inhibitor, GSK2230413. BALB/c trachea allografts were transplanted into
      Syk-knockout (Syk(del/del) ) mice or wild-type C57BL/6 recipients treated with
      GSK2230413. At day 28, histological analysis revealed that in the Syk(del/del)
      and GSK2230413-treated C57BL/6 recipients, the graft lumen remained open compared
      with allografts transplanted into Syk-expressing (Syk(flox/flox) ) and placebo
      control-treated C57BL/6 recipients. Immunofluorescence showed lymphoid neogenesis
      with distinct B and T cell zones in control mice. In contrast, lymphoid
      neogenesis was absent and few B or T cells were found in Syk(del/del) and
      GSK2230413-treated mice. These observations suggest that inhibition of Syk may be
      a potential therapeutic strategy for the management of OB following lung
      transplantation. 

PMID- 26308241
TI  - The effectiveness of different neuroprotective agents in facial nerve injury: An
      experimental study.
AB  - OBJECTIVES/HYPOTHESIS: To examine and compare the neuroprotective effects of
      dexamethasone, oxytocin, and resveratrol administration on regeneration after
      facial nerve crush injury in a rat model. STUDY DESIGN: Prospective, randomized,
      controlled animal study. METHODS: A crush-type facial nerve injury was performed
      on the right side of all rats (injury group [IG]), whereas there was no injury on
      the left side (sham group [SG]). These main groups were divided into five
      subgroups: 1) no medicine (control); 2) physiological serum; 3) dexamethasone; 4)
      oxytocin; and 5) resveratrol (Res) administered (intraperitoneal injection) for
      28 days. Functional recovery was evaluated by daily eye-blink reflex and facial
      electromyography. Nerve-muscle degeneration and regeneration, apoptosis, and
      intercellular connections were evaluated in histopathological and
      immunohistochemical examinations. RESULTS: Recovery time of the postinjury eye
      blink reflex demonstrated faster recovery in IG+Res when compared with the other
      subgroups. In peak-to-peak amplitude values, a significant increase was observed
      in the dexamethasone (P=0.007) and oxytocin subgroups (P=0.004) and was even more
      apparent in the resveratrol subgroup (P<0.001). Nerve regeneration is apparent in
      the resveratrol subgroup. Apoptotic changes were evaluated immunohistochemically
      with TUNEL and Caspase 3 and 6 antibodies staining. Caspase 3 and 6
      immunoexpressions of resveratrol and oxytocin subgroups were moderate when
      compared with dexamethasone subgroup. Except for the resveratrol subgroup, which
      had an increase in expression, the majority of subgroups were similar to SG in
      terms of intercellular connections (Connexin 32 and 43). CONCLUSION: Resveratrol
      leads to the best outcome after facial nerve crush injury in rats when compared
      with dexamethasone and oxytocin, even though these agents demonstrate a
      significant improvement in facial nerve regeneration. LEVEL OF EVIDENCE: N/A.

PMID- 26308242
TI  - Molecular biomarkers for chronological age in animal ecology.
AB  - The chronological age of an individual animal predicts many of its biological
      characteristics, and these in turn influence population-level ecological
      processes. Animal age information can therefore be valuable in ecological
      research, but many species have no external features that allow age to be
      reliably determined. Molecular age biomarkers provide a potential solution to
      this problem. Research in this area of molecular ecology has so far focused on a
      limited range of age biomarkers. The most commonly tested molecular age biomarker
      is change in average telomere length, which predicts age well in a small number
      of species and tissues, but performs poorly in many other situations. Epigenetic
      regulation of gene expression has recently been shown to cause age-related
      modifications to DNA and to cause changes in abundance of several RNA types
      throughout animal lifespans. Age biomarkers based on these epigenetic changes,
      and other new DNA-based assays, have already been applied to model organisms,
      humans and a limited number of wild animals. There is clear potential to apply
      these marker types more widely in ecological studies. For many species, these new
      approaches will produce age estimates where this was previously impractical. They
      will also enable age information to be gathered in cross-sectional studies and
      expand the range of demographic characteristics that can be quantified with
      molecular methods. We describe the range of molecular age biomarkers that have
      been investigated to date and suggest approaches for developing the newer marker
      types as age assays in nonmodel animal species. 

PMID- 26308243
TI  - Identification and reduction of image artifacts in non-contrast-enhanced velocity
      selective peripheral angiography at 3T.
AB  - PURPOSE: To identify and reduce image artifacts in non-contrast-enhanced velocity
      selective (VS) magnetization-prepared peripheral MR angiography (MRA) at 3T.
      METHODS: To avoid signal loss in the arteries, double and quadruple refocused VS
      excitation pulse sequences were designed that were robust to a wide range of B0
      and B1 offset. To suppress stripe artifact and background signal variation, we
      successively applied two VS preparations with excitation profiles shifted by half
      the period of the stripes. VS-MRA using single, double, and quadruple refocused
      VS preparations was tested in healthy subjects and a patient. RESULTS: In the
      regions of large B0 and B1 offsets, arterial signal loss was yielded by single
      refocused VS preparation, but was avoided with double or quadruple refocused
      preparations. Compared with single VS preparation, the two consecutive
      preparations with shifted excitation profiles substantially reduced the stripe
      artifact and background signal variation, as demonstrated by increased mean and
      decreased standard deviation of relative contrast-to-noise ratio. The proposed VS
      MRA identified multilevel disease in the femoral arteries of the patient, as
      validated by digital subtraction angiography. CONCLUSION: Two multiple refocused
      VS magnetization preparations with shifted excitation profiles yield artifact
      free peripheral angiograms at 3T. Magn Reson Med 76:466-477, 2016. (c) 2015 Wiley
      Periodicals, Inc.

PMID- 26308245
TI  - The Dural AV-Fistula (DAVF), the Most Frequent Acquired Vascular Malformation of
      the Central Nervous System (CNS).
AB  - Acquired arteriovenous malformations, such as is the case with dural
      arteriovenous fistulae (DAVF), are the consequence of a pathological new arterial
      ingrowth into venous spaces that reaches directly the venous lumen, without
      interposition of a capillary network, thereby creating an AV-shunt.The following
      concise text will provide elements in regards to diagnosis, indication for
      treatment discussion and choice of endovascular treatment (EVT) method.

PMID- 26308244
TI  - Revisiting determinants of prognosis in cutaneous melanoma.
AB  - The American Joint Committee on Cancer staging system for cutaneous melanoma is
      based on primary tumor thickness and the presence of ulceration, mitoses, lymph
      node spread, and distant metastases as determinants of prognosis. Although this
      cutaneous melanoma staging system has evolved over time to more accurately
      reflect patient prognosis, improvements are still needed, because current
      understanding of the particular factors (genetic mutation, expression alteration,
      host response, etc) that are critical for predicting patient outcomes is
      incomplete. Given the clinical and biologic heterogeneity of primary melanomas,
      new prognostic tools are needed to more precisely identify patients who are most
      likely to develop advanced disease. Such tools would affect clinical surveillance
      strategies and aid in patient selection for adjuvant therapy. The authors
      reviewed the literature on prognostic molecular and immunologic markers in
      primary cutaneous melanoma, their associations with clinicopathologic and
      survival outcomes, and their potential for incorporation into current staging
      models. Overall, the studies considered in this review did not define prognostic
      markers that could be readily incorporated into the current staging system.
      Therefore, efforts should be continued in these and other directions to maximize
      the likelihood of identifying clinically useful prognostic biomarkers for
      cutaneous melanoma.

PMID- 26308246
TI  - A Short Introduction to Arterial Spin Labeling and its Application to Flow
      Territory Mapping.
AB  - Arterial spin labeling (ASL) is an emerging method for the assessment of
      perfusion in various diseases of the brain. In ASL, the magnetization of arterial
      blood water spins is manipulated in a complete non-invasive way before flowing
      into the tissue of interest. This allows absolute quantification of cerebral
      blood flow, thereby, presenting an alternative to contrast-enhanced methods based
      on computed tomography or magnetic resonance imaging. Furthermore, its potential
      application for flow territory mapping can provide additional information of the
      individual configuration of intracerebral blood flow. This article gives a brief
      overview of the basic ASL methodology and its approaches to image individual
      perfusion territories. Additionally, the utilization of ASL in a variety of
      cerebrovascular diseases is presented to provide examples of potential
      applications of (territorial) ASL in clinical routine. 

PMID- 26308247
TI  - [Not Available].
AB  - CT-angiography (CTA) has been accredited as an additional technical method for
      the detection of the cessation of cerebral blood circulation in the updated
      German guidelines for the determination of irreversible loss of brain function. A
      standardized CTA protocol was defined. The evaluation of the CTA has to be done
      by radiologists with several years of experience in neuroradiology, preferably by
      radiologists certified as neuroradiologists. The so-called "stasis filling", a
      slow progressive spread of contrast media into the cerebral arteries despite
      cessation of cerebral blood circulation, has to be considered. 

PMID- 26308248
TI  - [Not Available].

PMID- 26308249
TI  - Effect of Liver Transplant on Long-term Disease-Free Survival in Children With
      Hepatoblastoma and Hepatocellular Cancer.
AB  - INTRODUCTION: Hepatoblastoma (HBL) and hepatocellular cancer (HCC) are the most
      common primary hepatic malignant neoplasms in childhood. Given the rarity of
      these childhood tumors and their propensity to present at advanced stages,
      updated long-term data are needed. OBJECTIVE: To determine the efficacy of liver
      transplant in children with HBL or HCC. DESIGN, PARTICIPANTS, AND SETTING: This
      single-institution retrospective medical record review and analysis spanned from
      January 1, 1997, through September 17, 2014, at Stanford University School of
      Medicine. A total of 40 patients younger than 18 years underwent liver transplant
      for treatment of HBL (n = 30) or HCC (n = 10) during the study period, with
      follow-up until September 17, 2014. Patients who underwent transplant for HCC
      included those with tumors that were greater in size than what is proposed by the
      Milan (a single tumor measuring <=5 cm or <=3 nodules measuring <=3 cm) and
      University of California, San Francisco (single tumor measuring <=6.5 cm or <=3
      nodules measuring <=4.5 cm and a total diameter of <=8 cm), criteria. MAIN
      OUTCOMES AND MEASURES: Disease-free and overall patient survival and graft
      survival. RESULTS: Using a Kaplan-Meier survival analysis, 1-, 5-, and 10-year
      disease-free survival after liver transplant was 93%, 82%, and 82%, respectively,
      for 30 patients with HBL and 90%, 78%, and 78%, respectively, for 10 patients
      with HCC. Risk factors associated with HBL recurrence after transplant included
      having pretreatment extent of disease stage IV lesions and a longer waiting list
      time and being older at the time of the transplant. Recurrence was found in 2 of
      7 patients with HBL and pretransplant metastases, which were not found to be an
      independent risk factor for recurrence. Patients with HCC larger than the
      proposed Milan and University of California, San Francisco, criteria experienced
      good 5-year disease-free (82%) and overall (78%) survival after transplant. Being
      older at the time of transplant (18 vs 11 years; P = .04) and the presence of
      metastatic disease (1 patient vs none; P = .05) were associated with HCC tumor
      recurrence. CONCLUSIONS AND RELEVANCE: Liver transplant combined with
      chemotherapy is an excellent treatment that provides long-term disease-free
      survival in children diagnosed with advanced HBL and HCC. Early addition to a
      waiting list and aggressive multimodal therapy provide excellent results.
      Transplant should still be considered in children with HCC larger than the Milan
      and University of California, San Francisco, criteria.

PMID- 26308251
TI  - Primary tentorial liposarcoma.

PMID- 26308252
TI  - Juvenile xanthogranuloma of supra-sellar region: a rare presentation.

PMID- 26308250
TI  - Timing and extent of response in colorectal cancer: critical review of current
      data and implication for future trials.
AB  - The identification of new surrogate endpoints for advanced colorectal cancer is
      becoming crucial and, along with drug development, it represents a research field
      increasingly studied. Although overall survival (OS) remains the strongest trial
      endpoint available, it requires larger sample size and longer periods of time for
      an event to happen. Surrogate endpoints such as progression free survival (PFS)
      or response rate (RR) may overcome these issues but, as such, they need to be
      prospectively validated before replacing the real endpoints; moreover, they often
      bear many other limitations. In this narrative review we initially discuss the
      role of time-to-event endpoints, objective response and response rate as
      surrogates of OS in the advanced colorectal cancer setting, discussing also how
      such measures are influenced by the tumor assessment criteria currently employed.
      We then report recent data published about early tumor shrinkage and deepness of
      response, which have recently emerged as novel potential endpoint surrogates,
      discussing their strengths and weaknesses and providing a critical comment.
      Despite being very compelling, the role of such novel response measures is yet to
      be confirmed and their surrogacy with OS still needs to be further investigated
      within larger and well-designed trials. 

PMID- 26308253
TI  - A case report of meningeal Rosai-Dorfman disease associated with IgG4-related
      disease.
AB  - AIMS: Rosai-Dorfman disease is a rare entity that has been described as
      lymphadenopathy in young patients. Extranodal forms of this disease have been
      previously observed. The etiology of Rosai-Dorfman disease remains unknown,
      relationships with the IgG4-related sclerotic disease have been detected. Herein,
      a rare case of Rosai-Dorfman disease with meningeal involvement and IgG4-related
      sclerotic disease is reported. MATERIAL: A meningeal biopsy in a 35-year-old
      woman who had a 6-month history of intermittent headache was performed after MRI
      examination showing diffuse leptomeningeal enhancement without cerebral
      parenchymal involvement. RESULTS: A mixed infiltration of lymphocytes, plasma
      cells, and histiocytes exhibiting emperipolesis was identified. The stroma was
      fibrous. Immunohistochemical analysis revealed a high number of IgG4-positive
      plasma cells and a rate of IgG4/IgG-positive plasma cells higher than 50%.
      CONCLUSION: The pathological results in this patient with meningeal infiltration
      are suggestive of Rosai-Dorman disease associated with IgG4-related disease. This
      observation further confirms the link between these two entities.

PMID- 26308254
TI  - Massive dissemination of adult glioblastomas.
AB  - BACKGROUND: Recent autopsy data suggests a high incidence of leptomeningeal
      metastases (LM), Acta Neuropathologica 2014; 128: 573 and subventricular spread
      (SVS), Acta Neuropathologica 2014; 127: 605 in pediatric diffuse intrinsic
      pontine gliomas, but both LM and SVS also occur in adult glioblastoma (GBM).
      Autopsy is required to fully appreciate this tumor behavior. METHODS: From
      January 1, 2014 to January 3, 2015 we conducted 239 adult autopsies, 8 of which
      were identified on search to be GBMs. RESULTS: Of these 8 GBMs, one-half showed
      bulky spread (SVS (n = 2), LM (n = 2), bone marrow (n = 1)), and 2 of these 4
      additionally had microscopic LM. In patient 1 GBM with a very minor epithelioid
      component on the surgical specimen spread evolved to a predominantly epithelioid
      GBM (E-GBM) phenotype in the clinically-unsuspected LM at autopsy. Patient 2,
      with malignant glioma with primitive neuroectodermal tumor (MGPNET), had a
      secondary GBM with a noncanonical isocitrate dehydrogenase 1 (IDH1) mutation and
      11-year-survival; autopsy showed encasement of the entire bilateral ventricular
      system by SVS. Patient 3, also with an IDH1- positive secondary GBM, had survived
      10 years, only to develop thrombocytopenia and succumb to extensive bone marrow
      replacement by his tumor. Patient 4 had a radiation-induced posterior fossa GBM
      that demonstrated LM/SVS spread pattern identical to that described in pediatric
      diffuse pontine gliomas. CONCLUSIONS: Several subtypes of adult GBM (MG-PNET,
      posterior fossa GBMs, E-GBMs) have recently been recognized to have a propensity
      for LM; autopsy permission should especially be sought for these tumor types.
      Correlation between genetics and LM/SVS is now possible and may shed further
      light on this behavior.

PMID- 26308255
TI  - Extensive full-thickness eyelid reconstruction with rotation flaps through
      "subcutaneous tunnel" and palatal mucosal grafts.
AB  - AIM: To reconstruct the extensive full-thickness defects of eyelids is a
      challenge for the plastic surgeon because of their complex anatomy and special
      functions. This article presents and discusses an improved surgical technique in
      which the orbicularis oculi myocutaneous flap is rotated through a "subcutaneous
      tunnel" in conjunction with a palatal mucosal graft employed for lining. METHODS:
      Data from 22 eyes with extensive full-thickness eyelid defects from various
      causes between 2009 and 2013 were analyzed in this study. After the different
      layers of eyelid were separated completely, a temporally based orbicularis oculi
      myocutaneous flap was designed following fishtail lines and was mobilized,
      leaving the base of the pedicle intact with a submuscular tissue attachment. The
      flap was then rotated through a "subcutaneous tunnel" to the defect, and the
      donor site was closed primarily. Posterior lamellar reconstruction was performed
      with a mucosal graft harvested from the hard palate. RESULTS: All the flaps were
      survived without any healing problems. There was no corneal irritation, flap
      contraction, or significant donor-site morbidity in the follow-up period. The
      incision scars were almost invisible. The defects were repaired completely, and
      the evaluations showed satisfactory function and appearance. CONCLUSION: This
      technique is an improved single-stage operation and can be applied to repair
      large, full-thickness eyelid defects from various causes. With our method, the
      functional and aesthetic results can be obtained in either the upper or lower
      eyelids.

PMID- 26308256
TI  - Packed column supercritical fluid chromatography using stainless steel particles
      and water as a stationary phase.
AB  - Stainless steel (SS) particles were demonstrated as a novel useful support for a
      water stationary phase in packed column supercritical fluid chromatography using
      a CO2 mobile phase. Separations employed flame ionization detection, and the
      system was operated over a range of temperatures and pressures. Retention times
      reproduced well with RSD values of 2.6% or less. Compared to analogous
      separations employing a water stationary phase coated onto a SS capillary column,
      the packed column method provided separations that were about 10* faster, with
      nearly 8-fold larger analyte retention factors, while maintaining good peak shape
      and comparable column efficiency. Under normal operating conditions, the packed
      column contains about 131 +/- 4 MUL/m of water phase (around a 5% m/m coating),
      which is over 25* greater than the capillary column and also affords it a 20-fold
      larger sample capacity. Several applications of the packed column system are
      examined, and the results indicate that it is a useful alternative to the
      capillary column mode, particularly where analyte loads or sample matrix
      interference is a concern. Given its high sample capacity, this packed column
      method may also be useful to explore on a more preparative scale in the future. 

PMID- 26308257
TI  - Repeated Kicking Actions in Karate: Effect on Technical Execution in Elite
      Practitioners.
AB  - PURPOSE: Training in martial arts is commonly performed by repeating a technical
      action continuously for a given number of times. This study aimed to investigate
      if the repetition of the task alters the proper technical execution, limiting the
      training efficacy for the technical evaluation during competition. This aim was
      pursued analyzing lower-limb kinematics and muscle activation during repeated
      roundhouse kicks. METHODS: Six junior karate practitioners performed continuously
      20 repetitions of the kick. Hip and knee kinematics and sEMG of vastus lateralis,
      biceps (BF), and rectus femoris were recorded. For each repetition, hip abduction
      adduction and flexion-extension and knee flexion-extension peak angular
      displacements and velocities, agonist and antagonist muscle activation were
      computed. Moreover, to monitor for the presence of myoelectric fatigue, if any,
      the median frequency of the sEMG was computed. All variables were normalized with
      respect to their individual maximum observed during the sequence of kicks. Linear
      regressions were fitted to each normalized parameter to test its relationship
      with the repetition number. RESULTS: Linear-regression analysis showed that,
      during the sequence, the athletes modified their technique: Knee flexion, BF
      median frequency, hip abduction, knee-extension angular velocity, and BF
      antagonist activation significantly decreased. Conversely, hip flexion increased
      significantly. CONCLUSIONS: Since karate combat competitions require proper
      technical execution, training protocols combining severe fatigue and technical
      actions should be carefully proposed because of technique adaptations. Moreover,
      trainers and karate masters should consider including specific strength exercises
      for the BF and more generally for knee flexors.

PMID- 26308258
TI  - Minimum Marriage Age Laws and the Prevalence of Child Marriage and Adolescent
      Birth: Evidence from Sub-Saharan Africa.
AB  - CONTEXT: The relationship of national laws that prohibit child marriage with the
      prevalence of child marriage and adolescent birth is not well understood.
      METHODS: Data from Demographic and Health Surveys and from the Child Marriage
      Database created by the MACHEquity program at McGill University were used to
      examine the relationship between laws that consistently set the age for marriage
      for girls at 18 or older and the prevalence of child marriage and teenage
      childbearing in 12 Sub-Saharan African countries. Countries were considered to
      have consistent laws against child marriage if they required females to be 18 or
      older to marry, to marry with parental consent and to consent to sex.
      Associations between consistent laws and the two outcomes were identified using
      multivariate regression models. RESULTS: Four of the 12 countries had laws that
      consistently set the minimum age for marriage at 18 or older. After adjustment
      for covariates, the prevalence of child marriage was 40% lower in countries with
      consistent laws against child marriage than in countries without consistent laws
      against the practice (prevalence ratio, 0.6). The prevalence of teenage
      childbearing was 25% lower in countries with consistent minimum marriage age laws
      than in countries without consistent laws (0.8). CONCLUSION: Our results support
      the hypothesis that consistent minimum marriage age laws protect against the
      exploitation of girls.

PMID- 26308259
TI  - Quality of Care and Contraceptive Use in Urban Kenya.
AB  - CONTEXT: Family planning is highly beneficial to women's overall health,
      particularly in developing countries. Yet, in much of Sub-Saharan Africa,
      contraceptive prevalence remains low and unmet need for family planning remains
      high. It is hypothesized that the poor quality of family planning service
      provision in many low-income settings is a barrier to contraceptive use, but this
      hypothesis has not been rigorously tested. METHODS: Survey data from 3,990 women
      were used to investigate whether family planning service quality was associated
      with current modern contraceptive use in five cities in Kenya in 2010. In
      addition, audits of selected facilities and service provider interviews were
      conducted in 260 facilities, and exit interviews were conducted with family
      planning clients at 126 high-volume clinics. Individual- and facility-level data
      were linked according to the source of the woman's current method or other health
      service. Binomial regression was used to estimate adjusted prevalence ratios, and
      robust standard errors were used to account for clustering of observations within
      facilities. RESULTS: Sixty-five percent of women reported currently using a
      modern contraceptive method. Provider's solicitation of clients' method
      preferences, assistance with method selection, provision of information on side
      effects and good treatment of clients were positively associated with current
      modern contraceptive use (prevalence ratios, 1.1 each); associations were often
      stronger among younger and less educated women. CONCLUSION: Efforts to assist
      with method selection and to improve the content of contraceptive counseling and
      treatment of clients by providers have the potential to increase contraceptive
      use in urban Kenya.

PMID- 26308260
TI  - Is Unwanted Birth Associated with Child Malnutrition in Bangladesh?
AB  - CONTEXT: The association between unintended pregnancy and maternal and child
      health has been well documented. However, the relationship of unintended
      pregnancy with child malnutrition is not well understood, and may be important in
      countries such as Bangladesh that have high levels of these events. METHODS: Data
      from the 2011 Bangladesh Demographic and Health Survey on 6,506 last-born,
      singleton children younger than five were used to investigate the relationship
      between pregnancy intendedness and the prevalence of stunting, wasting and
      underweight during early childhood. Multivariate logistic regression analyses
      were used to identify associations. RESULTS: Substantial proportions of children
      were stunted (40%), wasted (16%) and underweight (35%) at the time of the survey.
      Mothers reported that at the time of conception, 14% of their index pregnancies
      had been unwanted and 16% had been mistimed. Compared with children whose
      conception had been intended, those whose conception had been unwanted were more
      likely to be stunted (46% vs. 39%), wasted (19% vs. 15%) or underweight (43% vs.
      33%). In regression analyses, children who had been unwanted at the time of
      conception had an elevated risk of being stunted (odds ratio, 1.4), wasted (1.4)
      or underweight (1.3). CONCLUSION: Maternal pregnancy intentions are associated
      with child stunting, wasting and underweight. If these associations are causal,
      preventing unwanted pregnancies may help reduce the prevalence of childhood
      malnutrition in Bangladesh.

PMID- 26308261
TI  - Dynamic Relationships Between Parental Monitoring, Peer Risk Involvement and
      Sexual Risk Behavior Among Bahamian Mid-Adolescents.
AB  - CONTEXT: Considerable research has examined reciprocal relationships between
      parenting, peers and adolescent problem behavior; however, such studies have
      largely considered the influence of peers and parents separately. It is important
      to examine simultaneously the relationships between parental monitoring, peer
      risk involvement and adolescent sexual risk behavior, and whether increases in
      peer risk involvement and changes in parental monitoring longitudinally predict
      adolescent sexual risk behavior. METHODS: Four waves of sexual behavior data were
      collected between 2008/2009 and 2011 from high school students aged 13-17 in the
      Bahamas. Structural equation and latent growth curve modeling were used to
      examine reciprocal relationships between parental monitoring, perceived peer risk
      involvement and adolescent sexual risk behavior. RESULTS: For both male and
      female youth, greater perceived peer risk involvement predicted higher sexual
      risk behavior index scores, and greater parental monitoring predicted lower
      scores. Reciprocal relationships were found between parental monitoring and
      sexual risk behavior for males and between perceived peer risk involvement and
      sexual risk behavior for females. For males, greater sexual risk behavior
      predicted lower parental monitoring; for females, greater sexual risk behavior
      predicted higher perceived peer risk involvement. According to latent growth
      curve models, a higher initial level of parental monitoring predicted decreases
      in sexual risk behavior, whereas both a higher initial level and a higher growth
      rate of peer risk involvement predicted increases in sexual risk behavior.
      CONCLUSION: Results highlight the important influence of peer risk involvement on
      youths' sexual behavior and gender differences in reciprocal relationships
      between parental monitoring, peer influence and adolescent sexual risk behavior.

PMID- 26308262
TI  - Sexual Pleasure, Partner Dynamics and Contraceptive Use in Malawi.
AB  - CONTEXT: Despite increases in the use of modern contraceptives, Malawian women
      have a high unmet need for contraception. Because current understanding of
      contraceptive use ignores sexual pleasure and partner dynamics, this study
      explores the links between sexual pleasure seeking, partner dynamics and
      contraceptive use. METHODS: As part of a larger qualitative study conducted in
      2012, 23 focus group discussions among married women and men and 10 in-depth
      interviews with service providers were conducted with a total of 192 participants
      in two districts of Malawi. Thematic analysis was performed to identify recurrent
      categories and patterns. RESULTS: Method choice and consistent use were affected
      by the quantity and quality of sex desired and, most important, by any perceived
      change in sexual pleasure for respondents or their partner. For women, more so
      than for men, experiences of sexual pleasure were intertwined with gender norms,
      women's perceived role of providing pleasure in sexual relationships and the
      relationship dynamics this generated. These partner dynamics ultimately created a
      formidable barrier to contraceptive use or promoted contraceptive
      discontinuation. CONCLUSION: Family planning programs should consider the nuanced
      ways in which notions of sexual pleasure, partner dynamics and the broader social
      context are involved in decision making regarding contraceptive use.

PMID- 26308263
TI  - Estrogenic activity data extraction and in silico prediction show the endocrine
      disruption potential of bisphenol A replacement compounds.
AB  - Bisphenol A (BPA) replacement compounds are released to the environment and cause
      widespread human exposure. However, a lack of thorough safety evaluations on the
      BPA replacement compounds has raised public concerns. We assessed the endocrine
      disruption potential of BPA replacement compounds in the market to assist their
      safety evaluations. A literature search was conducted to ascertain the BPA
      replacement compounds in use. Available experimental estrogenic activity data of
      these compounds were extracted from the Estrogenic Activity Database (EADB) to
      assess their estrogenic potential. An in silico model was developed to predict
      the estrogenic activity of compounds lacking experimental data. Molecular
      dynamics (MD) simulations were performed to understand the mechanisms by which
      the estrogenic compounds bind to and activate the estrogen receptor (ER). Forty
      five BPA replacement compounds were identified in the literature. Seven were more
      estrogenic and five less estrogenic than BPA, while six were nonestrogenic in
      EADB. A two-tier in silico model was developed based on molecular docking to
      predict the estrogenic activity of the 27 compounds lacking data. Eleven were
      predicted as ER binders and 16 as nonbinders. MD simulations revealed hydrophobic
      contacts and hydrogen bonds as the main interactions between ER and the
      estrogenic compounds. 

PMID- 26308264
TI  - Harpagoside Inhibits RANKL-Induced Osteoclastogenesis via Syk-Btk-PLCgamma2
      Ca(2+) Signaling Pathway and Prevents Inflammation-Mediated Bone Loss.
AB  - Harpagoside (HAR) is a natural compound isolated from Harpagophytum procumbens
      (devil's claw) that is reported to have anti-inflammatory effects; however, these
      effects have not been investigated in the context of bone development. The
      current study describes for the first time that HAR inhibits receptor activator
      of nuclear factor kappaB ligand (RANKL)-induced osteoclastogenesis in vitro and
      suppresses inflammation-induced bone loss in a mouse model. HAR also inhibited
      the formation of osteoclasts from mouse bone marrow macrophages (BMMs) in a dose
      dependent manner as well as the activity of mature osteoclasts, including
      filamentous actin (F-actin) ring formation and bone matrix breakdown. This
      involved a HAR-induced decrease in extracellular signal-regulated kinase (ERK)
      and c-jun N-terminal kinase (JNK) phosphorylation, leading to the inhibition of
      Syk-Btk-PLCgamma2-Ca(2+) in RANKL-dependent early signaling, as well as the
      activation of c-Fos and nuclear factor of activated T cells cytoplasmic 1
      (NFATc1), which resulted in the down-regulation of various target genes.
      Consistent with these in vitro results, HAR blocked lipopolysaccharide (LPS)
      induced bone loss in an inflammatory osteoporosis model. However, HAR did not
      prevent ovariectomy-mediated bone erosion in a postmenopausal osteoporosis model.
      These results suggest that HAR is a valuable agent against inflammation-related
      bone disorders but not osteoporosis induced by hormonal abnormalities. 

PMID- 26308266
TI  - ["Relief for family caregivers" - conceptual revision].

PMID- 26308265
TI  - Sequential Drug Release and Enhanced Photothermal and Photoacoustic Effect of
      Hybrid Reduced Graphene Oxide-Loaded Ultrasmall Gold Nanorod Vesicles for Cancer
      Therapy.
AB  - We report a hybrid reduced graphene oxide (rGO)-loaded ultrasmall plasmonic gold
      nanorod vesicle (rGO-AuNRVe) (~65 nm in size) with remarkably amplified
      photoacoustic (PA) performance and photothermal effects. The hybrid vesicle also
      exhibits a high loading capacity of doxorubicin (DOX), as both the cavity of the
      vesicle and the large surface area of the encapsulated rGO can be used for
      loading DOX, making it an excellent drug carrier. The loaded DOX is released
      sequentially: near-infrared photothermal heating induces DOX release from the
      vesicular cavity, and an intracellular acidic environment induces DOX release
      from the rGO surface. Positron emission tomography imaging showed high passive
      U87MG tumor accumulation of (64)Cu-labeled rGO-AuNRVes (~9.7% ID/g at 24 h
      postinjection) and strong PA signal in the tumor region. Single intravenous
      injection of rGO-AuNRVe-DOX followed by low-power-density 808 nm laser
      irradiation (0.25 W/cm(2)) revealed effective inhibition of tumor growth due to
      the combination of chemo- and photothermal therapies. The rGO-AuNRVe-DOX capable
      of sequential DOX release by laser light and acid environment may have the
      potential for clinical translation to treat cancer patients with tumors
      accessible by light. 

PMID- 26308267
TI  - [Nursing care in the run-up to Swiss DRG - Nurses' experiences with
      interprofessional collaboration, leadership, work load and job satisfaction].
AB  - BACKGROUND: The literature reports critically on the consequences of the
      introduction of case-based hospital reimbursement systems, which hamper the
      delivery of professional nursing care. For this reason, we examined the
      characteristics of nursing service context factors (work environment factors) in
      acute care hospitals with regards to the introduction of the new reimbursement
      system in Switzerland. AIM: This qualitative study describes practice experiences
      of nurses in the context of the characteristics of the nursing service context
      factors interprofessional collaboration, leadership, workload and job
      satisfaction. METHODS: Twenty focus group interviews were conducted with a total
      of 146 nurses in five acute care hospitals. RESULTS: The results indicated that
      for quite some time the participants had observed an increase in complexity of
      nursing care and a growing invasiveness of clinical diagnostics and treatment. At
      the same time they noticed a decrease in patient length of stay. They strived to
      offer high quality nursing care even in situations where demands outweighed
      resources. Good interprofessional collaboration and supportive leadership
      contributed substantially to nurses' ability to overcome daily challenges. Job
      satisfaction was bolstered by interactions with patients. Also, the role played
      by the nursing team itself is not to be underestimated. CONCLUSIONS: From the
      participants' point of view, context factors harbor great potential for attaining
      positive patient outcomes and higher job satisfaction and have to be monitored
      repeatedly.

PMID- 26308268
TI  - [Influence and correlation of attitude, availability and institutional support to
      research implementation in nursing practice - results from an exploratory, cross
      sectional quantitative study].
AB  - BACKGROUND: The concrete application of research findings in nursing practice is
      a multidimensional process. In Austria, there are currently no results available
      that explain the impact of and association with the implementation of research in
      hospitals. OBJECTIVE: The aim of the study was to investigate influences and
      relationships of individual attitudes towards research utilization, availability
      of research results and institutional support of nurses in Austrian hospitals
      with respect to research application. METHODS: In a non-experimental quantitative
      cross-sectional design a multi-centre study (n = 10) was performed in 2011.
      RESULTS: The sample comprises 178 certified nurses who were interviewed with a
      survey questionnaire. The multiple regression analysis shows that a positive
      attitude towards research use (beta = 0.388, p < 0.001), the availability of
      processed research results (beta = 0.470, p < 0.001), and an adequate
      institutional support (beta = 0.142, p < 0.050) has a significant influence on
      the application of research results. The path analysis proves that course
      attendance in evidence-based nursing has a strong positive influence towards
      research application (beta = 0.464; p < 0.001). CONCLUSIONS: Health institutions
      are, according to legal instructions, called on to make use of the positive
      attitude and supply supporting measures in order to introduce research results
      into the daily nursing practice.

PMID- 26308269
TI  - [Content validation of the questionnaire "The Management of Aggression in People
      with Dementia Attitude Questionnaire German Version" (MAPDAQ-G)].
AB  - BACKGROUND: Dementia is one of the most common diseases of aging and leads to an
      increased need for care. Caregivers' attitudes about aggression can influence
      their interaction with people with dementia. To examine this further, "The
      Management of Aggression in People with Dementia Attitude Questionnaire" (MAPDAQ)
      was developed for use in nursing homes in the United Kingdom. In Switzerland, the
      MAPDAQ has been translated into a German Version (MAPDAQ-G), but not yet tested
      for its validity and reliability. AIM: Therefore the present study examined the
      content and face validity, comprehensibility and interpretability of MAPDAQ-G in
      a Swiss context. METHODS: The review was based on expert surveys and interviews
      with caregivers in nursing homes and psychiatric hospitals. RESULTS: According to
      experts, the optimised MAPDAQ-G is comprehensive (88 %) and shows good content
      validity (I-CVI = 0,6 - 0,1; S-CVI-Ave = 0,88). 15 items have been adapted and
      further validated by 16 nurses. Finally, apart from two items, the MAPDAQ-G is
      understood by nurses and can be interpreted consistently. CONCLUSIONS: A
      questionnaire of this sort allows nurses to reflect in practice upon their own
      attitude with regard to the management of aggression in people with dementia and
      to influence the quality of care. The MAPDAQ-G should be statistically tested for
      validity and reliability using a larger sample.

PMID- 26308270
TI  - [Prevention of sudden infant death as a task of nurses in neonatology -
      Evaluations and recommendations as a result of a cross-sectional survey].
AB  - BACKGROUND: The sudden infant death is a diagnosis by exclusion and a
      multifactorial event. Premature infants are at a high risk. They must be
      especially protected from additional risk factors. Prevention campaigns support
      the decrease of mortality rate. The study aims to demonstrate various aspects of
      procedure applied by nurses and within neonatal units in SIDS prevention and
      counseling. SAMPLE AND METHODS: In the nine level 1 perinatal centres of a german
      federal state, the study aims to examine the neonatological nurse's knowledge of
      prevention aspects of sudden infant death. The aim is not only to contemplate the
      individual nurse, but also the institutional framework of the respective clinics
      is considered. The cross-sectional survey was done with help of a written survey.
      RESULTS: 165 nurses participated (160 female, four male, one unknown). Premature
      infants do not consistently get accustomed to the supine position. 33 percent of
      the nurses evaluate breastfeeding as very important. 74 percent regularly talk to
      parents about prevention. Half of the nurses do not record the counseling
      interviews. CONCLUSION: Although evidence based recommendations to prevent sudden
      infant death exist they are not executed consequently. The motives for the
      inadequate implementation should be determined. Trainings should focus on the
      mediation of protective factors. Nurses should also demonstrate preventive
      interventions and support parents in putting these actions into practice.

PMID- 26308271
TI  - [Interventions for prevention and reduction of the leisure limiting measures in
      inpatient geriatric nursing: challenges in the synthesis of complex
      interventions].

PMID- 26308272
TI  - [Measurement of nursing care needs - from routine data or separate calculation?].

PMID- 26308273
TI  - ["Nurse migration" topic emphasis].

PMID- 26308277
TI  - Metal-Polycyclic Aromatic Hydrocarbon Mixture Toxicity in Hyalella azteca. 1.
      Response Surfaces and Isoboles To Measure Non-additive Mixture Toxicity and
      Ecological Risk.
AB  - Mixtures of metals and polycyclic aromatic hydrocarbons (PAHs) occur ubiquitously
      in aquatic environments, yet relatively little is known regarding their potential
      to produce non-additive toxicity (i.e., antagonism or potentiation). A review of
      the lethality of metal-PAH mixtures in aquatic biota revealed that more-than
      additive lethality is as common as strictly additive effects. Approaches to
      ecological risk assessment do not consider non-additive toxicity of metal-PAH
      mixtures. Forty-eight-hour water-only binary mixture toxicity experiments were
      conducted to determine the additive toxic nature of mixtures of Cu, Cd, V, or Ni
      with phenanthrene (PHE) or phenanthrenequinone (PHQ) using the aquatic amphipod
      Hyalella azteca. In cases where more-than-additive toxicity was observed, we
      calculated the possible mortality rates at Canada's environmental water quality
      guideline concentrations. We used a three-dimensional response surface isobole
      model-based approach to compare the observed co-toxicity in juvenile amphipods to
      predicted outcomes based on concentration addition or effects addition mixtures
      models. More-than-additive lethality was observed for all Cu-PHE, Cu-PHQ, and
      several Cd-PHE, Cd-PHQ, and Ni-PHE mixtures. Our analysis predicts Cu-PHE, Cu
      PHQ, Cd-PHE, and Cd-PHQ mixtures at the Canadian Water Quality Guideline
      concentrations would produce 7.5%, 3.7%, 4.4% and 1.4% mortality, respectively.

PMID- 26308278
TI  - Systematic review of the recent evidence for the efficacy and safety of
      chlorambucil in the treatment of B-cell malignancies.
AB  - Emergence of new agents has deeply modified treatment options and the role of
      chlorambucil (CLB) in B-cell malignancies. We conducted a systematic review of
      prospective, randomized, controlled trials (RCTs) investigating the benefits and
      harms of CLB used alone or in combination with other treatment in patients
      suffering from chronic lymphocytic leukemia (CLL), low-grade non-Hodgkin lymphoma
      (NHL) or Waldenstrom macroglobulinemia (WM). For CLL, review of the nine RCTs
      showed that the main advantage of CLB is its low toxicity in comparison with
      purine nucleoside analogs like fludarabine in either CLL or NHL. In CLL, the
      major disadvantage is the very low rate of complete response, except when
      combining an anti-CD20 antibody. For B-cell lymphoma and WM, six RCTs were
      summarized. Results according to the usual criteria are presented and the role of
      CLB, used mostly in combination with an anti-CD20 antibody, is discussed for each
      indication, in particular for unfit patients. 

PMID- 26308279
TI  - A Common Flanking Region in Promiscuous Plasmids Encoding blaNDM-1 in Klebsiella
      pneumoniae Isolated in Singapore.
AB  - Bacteria encoding the New Delhi metallo-beta-lactamase gene (blaNDM-1) are
      regarded as superbugs for their resistance to multiple antibiotics. Plasmids
      encoding blaNDM-1 have been observed to be spreading among gram-negative bacteria
      around the world. Previous studies have demonstrated that multiple modifications
      of blaNDM-1-harboring plasmids might contribute to the spread of the gene. In
      this study, we analyzed blaNDM-1-encoding plasmids from two Klebsiella pneumoniae
      isolates, DU7433 and DU1301, found to be unrelated by pulsed field gel
      electrophoresis and multilocus sequencing typing (DU7433: ST14 and DU1301: ST11),
      and compared them with previously published plasmids. Although strains DU1301,
      DU7433, and previously published strain DU43320 carried unrelated plasmids, their
      transconjugants exhibited similar antimicrobial resistance profiles.
      Transconjugants lacked the resistance to aztreonam, ciprofloxacin, gentamicin,
      tetracycline, and trimethoprim/sulfamethoxazole when compared with the
      corresponding clinical isolates. Plasmids pTR1 from DU1301 and pTR2 from DU7433
      had completely different plasmid backbones except a short conserved region of
      blaNDM-1 and ble flanked with truncated or nontruncated ISAba125 and trpF. The
      presence of this common region among known blaNDM-1-carrying plasmids implies
      that the dissemination of blaNDM-1 may be facilitated by mobilization of this
      conserved immediate region among different plasmids. Control measures should be
      strictly enforced whenever increasing incidences of epidemiological unrelated
      strains were identified. 

PMID- 26308280
TI  - Energy-Efficient Phase-Change Memory with Graphene as a Thermal Barrier.
AB  - Phase-change memory (PCM) is an important class of data storage, yet lowering the
      programming current of individual devices is known to be a significant challenge.
      Here we improve the energy-efficiency of PCM by placing a graphene layer at the
      interface between the phase-change material, Ge2Sb2Te5 (GST), and the bottom
      electrode (W) heater. Graphene-PCM (G-PCM) devices have ~40% lower RESET current
      compared to control devices without the graphene. This is attributed to the
      graphene as an added interfacial thermal resistance which helps confine the
      generated heat inside the active PCM volume. The G-PCM achieves programming up to
      10(5) cycles, and the graphene could further enhance the PCM endurance by
      limiting atomic migration or material segregation at the bottom electrode
      interface. 

PMID- 26308281
TI  - Fundus Photography in the 21st Century--A Review of Recent Technological Advances
      and Their Implications for Worldwide Healthcare.
AB  - BACKGROUND: The introduction of fundus photography has impacted retinal imaging
      and retinal screening programs significantly. LITERATURE REVIEW: Fundus cameras
      play a vital role in addressing the cause of preventive blindness. More attention
      is being turned to developing countries, where infrastructure and access to
      healthcare are limited. One of the major limitations for tele-ophthalmology is
      restricted access to the office-based fundus camera. RESULTS: Recent advances in
      access to telecommunications coupled with introduction of portable cameras and
      smartphone-based fundus imaging systems have resulted in an exponential surge in
      available technologies for portable fundus photography. Retinal cameras in the
      near future would have to cater to these needs by featuring a low-cost, portable
      design with automated controls and digitalized images with Web-based transfer.
      CONCLUSIONS: In this review, we aim to highlight the advances of fundus
      photography for retinal screening as well as discuss the advantages,
      disadvantages, and implications of the various technologies that are currently
      available.

PMID- 26308282
TI  - Synthesis of Pt-Loaded Self-Interspersed Anatase TiO2 with a Large Fraction of
      (001) Facets for Efficient Photocatalytic Nitrobenzene Degradation.
AB  - TiO2 is capable of directly utilizing solar energy for sustainable energy harvest
      and water purification. Facet-dependent performance of TiO2 has attracted
      enormous interests due to its tunable photocatalytic activity toward photoredox
      transformations, but information about the noble-metal-loaded TiO2 for its facet
      dependent photocatalytic performance, especially in pollutant degradation
      systems, is limited. In this work, inspired by our previous theoretical
      calculations about the roles of the crystal surface in Pt-loaded TiO2 in its
      enhanced photocatalytic capacity, TiO2 nanocrystals with interspersed polyhedron
      nanostructures and coexposed (001) and (101) surfaces as a support of Pt
      nanoparticles are prepared in a simple and relatively green route. Also, their
      performance for photocatalytic degradation of nitrobenzene (NB), a model organic
      pollutant, is explored. The experimental results demonstrate that the NB
      photodegradation and photoconversion efficiencies are significantly enhanced by
      uniformly loading Pt nanoparticles on the crystal surfaces, but the Pt
      nanoparticles deposited on only the (101) surface have no contribution to the
      improved NB photodegradation. Furthermore, the liquid chromatography mass
      spectrometry results also show that NB photodegradation tends to proceed on the
      (001) surface of Pt/TiO2 for the generation of nitrophenol intermediates through
      the photooxidation pathway. This work provides a new route to design and
      construct advanced photocatalysts toward pollutant photoredox conversions and
      deepens our fundamental understanding about crystal surface engineering. 

PMID- 26308283
TI  - Immunogenicity and pharmacokinetics of short, proline-rich antimicrobial
      peptides.
AB  - AIM: The potential of proline-rich antimicrobial peptides (PrAMPs) to treat
      multidrug-resistant Gram-negative pathogens has been intensively investigated.
      They are efficacious at low doses in infection models and well tolerated in
      healthy mice at high doses. METHODS & RESULTS: PrAMPs Onc72 and Api88 were
      nonimmunogenic in mice unless conjugated to a carrier protein. Monoclonal
      IgG1/IgG2b antibodies produced by hybridoma cells were mapped to different Onc72
      regions and combined in a sandwich-ELISA in a pharmacokinetic study. Onc72 was
      detected at concentrations up to 32 ug/ml in murine blood after administering 20
      mg/kg and reached several organs within 10 min. CONCLUSION: Both PrAMPs were not
      immunogenic and Onc72 concentrations in blood were well above the minimal
      inhibitory concentrations for Enterobacteriaceae further confirming their
      potential as novel antibiotics.

PMID- 26308285
TI  - Tumor infiltrating lymphocyte therapy for ovarian cancer and renal cell
      carcinoma.
AB  - Personalized cancer immunotherapy based on infusion of T cells holds the promise
      to specifically target a patient's individual tumor. Accumulating evidence
      indicates that the T cells mediating these tumor regressions after cancer
      immunotherapies may primarily target patient-specific mutations expressed by the
      patients' tumors and that the presence of these "neo-antigen" specific T-cells
      may be related to a high number of mutations in the tumor. In melanoma, treatment
      with autologous tumor-infiltrating lymphocytes (TILs) can mediate durable
      complete responses. Previous trials investigating TIL therapy in solid tumors
      other than melanoma have shown limited success, however none of these early
      trials used current preparative chemotherapy regimens, and the methods for in
      vitro lymphocyte expansion have changed considerably. New advances and
      understandings in T cell based immunotherapies have stimulated the interest in
      developing this approach for other indications. Here, we summarize the early
      clinical data in the field of adoptive cell transfer therapy (ACT) using tumor
      infiltrating lymphocytes for patients with renal cell carcinoma (RCC) and ovarian
      cancer (OC). In addition we describe the major advances in the characterization
      and application of TIL therapy for patients with RCC and OC. 

PMID- 26308286
TI  - Intravitreal Triamcinolone Injection for Uveitic Macular Edema: A Randomized
      Clinical Study.
AB  - PURPOSE: To evaluate the additive effect of intravitrial triamcinolone (TA)
      injection in uveitic macular edema compared to systemic anti-inflammatory
      treatment only. METHODS: Patients were randomized into the intravitreal TA
      injection group and the sham group. All patients received systemic anti
      inflammatory treatment with follow-up monthly to 6 months, with additional
      treatment as needed. RESULTS: Fifty eyes of 50 patients were enrolled. Central
      foveal thickness decreased significantly from month 1 in the TA group, and from
      month 3 in the sham group. Parafoveal area thickness significantly decreased in
      both groups from month 1, with greater decrease in the TA group at months 2 and
      3. Leakage area on fluorescein angiography was significantly smaller in the TA
      group at months 1 to 3. Intraocular pressure increased in the TA group at months
      1 and 2. CONCLUSIONS: Intravitreal TA injection showed earlier reduction of
      leakage and retinal edema compared to systemic anti-inflammatory treatment alone.

PMID- 26308288
TI  - The synthesis of (Z)-4-oxo-4-(arylamino)but-2-enoic acids derivatives and
      determination of their inhibition properties against human carbonic anhydrase I
      and II isoenzymes.
AB  - The synthesis of (Z)-4-oxo-4-(arylamino)but-2-enoic acid (4) derivatives
      containing structural characteristics that can be used for the synthesis of
      several active molecules, is presented. Some of the butenoic acid derivatives
      (4a, 4c, 4e, 4i, 4j, 4k) are synthesized following literature procedures and at
      the end of the reaction. In addition, structures of all synthesized derivatives
      (4a-4m) were determined by (1)H-NMR, (13)C-NMR and IR spectroscopy. Carbonic
      anhydrase is a metalloenzyme involved in many crucial physiologic processes as it
      catalyzes a simple but fundamental reaction, the reversible hydration of carbon
      dioxide to bicarbonate and protons. Significant results were obtained by
      evaluating the enzyme inhibitory activities of these derivatives against human
      carbonic anhydrase hCA I and II isoenzymes (hCA I and II). Butenoic acid
      derivatives (4a-4m) strongly inhibited hCA I and II with Kis in the low nanomolar
      range of 1.85 +/- 0.58 to 5.04 +/- 1.46 nM against hCA I and in the range of 2.01
      +/- 0.52 to 2.94 +/- 1.31 nM against hCA II. 

PMID- 26308287
TI  - Efficacy of an in-home test kit in reducing dust mite allergen levels: results of
      a randomized controlled pilot study.
AB  - BACKGROUND: Dust mite allergens can induce allergic sensitization and exacerbate
      asthma symptoms. Although dust mite reduction and control strategies exist, few
      asthmatics employ them. OBJECTIVES: We examined whether an in-home test kit,
      which quantifies dust mite allergen levels, resulted in behavioral changes in
      implementation and maintenance of mite reduction strategies and helped reduce
      allergen levels in homes of dust mite-sensitive children. METHODS: We enrolled 60
      households of children aged 5-15 with parent-reported dust mite allergy into a
      randomized controlled trial. Intervention homes (N = 30) received educational
      material about reducing dust mites and test kits at 1, 2, 5 and 8 months. Control
      homes (N = 30) received only educational material. At baseline, 6 and 12 months,
      study staff visited all homes, collected dust samples from three locations and
      obtained information about parents' mite reduction behaviors by questionnaire.
      Allergen concentrations (Der f 2/Der p2) in dust were assessed by immunoassays.
      After adjusting for visit and location, allergen concentrations in intervention
      and control homes were compared using mixed effects model analysis. RESULTS: In
      the intervention homes, allergen concentrations in the child's bedroom and living
      room floors were significantly reduced over time compared to control homes.
      Although not all location-specific differences in allergen concentrations were
      statistically significant, combining data across locations, there was a
      differential reduction in allergen concentrations in the intervention group
      versus the control group (p = 0.02). CONCLUSION: The use of in-home test kits
      along with education may beneficially influence behaviors and attitudes toward
      dust mite reduction strategies and help reduce residential dust mite allergen
      levels.

PMID- 26308289
TI  - Proportion of Undercarboxylated Osteocalcin and Serum P1NP Predict Incidence of
      Myocardial Infarction in Older Men.
AB  - CONTEXT: Undercarboxylated osteocalcin (ucOC) modulates insulin secretion and
      sensitivity in mice, and higher ucOC is associated with lower prevalence of
      diabetes in men. The influence of ucOC distinct from other markers of bone
      turnover on incidence of cardiovascular events is unclear. PARTICIPANTS:
      Community-dwelling men aged 70-89 years resident in Perth, Western Australia.
      MAIN OUTCOME MEASURES: Serum total osteocalcin (TOC), N-terminal propeptide of
      type I collagen (P1NP), and collagen type I C-terminal cross-linked telopeptide
      (CTX) were measured by immunoassay, and ucOC by hydroxyapatite binding. The ratio
      ucOC/TOC was calculated. Hospital admissions and deaths from myocardial
      infarction (MI) and stroke were ascertained. RESULTS: There were 3384 men
      followed for 7.0 years, during which 293 experienced an MI, 251 stroke, and 2840
      neither. In multivariate analyses, higher ratio of ucOC/TOC (expressed as %) was
      associated with lower incidence of MI (quartiles Q2-4, >= 49% versus Q1,<49%,
      hazard ratio 0.70, 95% confidence interval = 0.54-0.91), but not of stroke (0.99,
      0.73-1.34). Higher P1NP was associated with higher incidence of MI (Q2-4, >= 28.2
      MUg/L versus Q1, <28.2 MUg/L, hazard ratio 1.45, 95% confidence interval = 1.06
      1.97), but not of stroke (0.94, 0.70-1.26). CTX was not associated with incident
      MI or stroke. CONCLUSIONS: A reduced proportion of undercarboxylated osteocalcin
      or higher P1NP are associated with increased incidence of MI. UcOC/TOC ratio and
      P1NP predict risk of MI but not stroke, in a manner distinct from CTX. Further
      studies are needed to investigate potential mechanisms by which bone turnover
      markers related to metabolic risk and to collagen formation could modulate
      cardiovascular risk.

PMID- 26308290
TI  - GnRH Agonist Triggering Modulates PEDF to VEGF Ratio Inversely to hCG in
      Granulosa Cells.
AB  - CONTEXT: GnRH agonist (GnRH-a) triggering is associated with a reduced risk of
      ovarian hyperstimulation syndrome (OHSS) compared with human chorionic
      gonadotropin (hCG) in assisted reproduction technology cycles. We have shown that
      ovarian pigment epithelium derived factor (PEDF), a potent antiangiogenic factor,
      counteracts vascular endothelial growth factor (VEGF) expression and that OHSS is
      correlated with hCG-induced impaired PEDF to VEGF ratio. OBJECTIVE: The objective
      of the study was to explore whether GnRH-a triggering could directly modulate
      PEDF/VEGF balance in granulosa cells. DESIGN: The design of the study was a mouse
      model and cultured granulosa cells. MAIN OUTCOME: Changes in PEDF and VEGF were
      measured by quantitative PCR and Western blot analysis. OHSS symptoms were
      recorded by changes in body weight and in peritoneal vascular leakage, quantified
      by the modified Miles vascular permeability assay. RESULTS: GnRH-a stimulation
      significantly increased PEDF and decreased VEGF mRNA and protein levels both in
      rat granulosa cell line and human primary granulosa cells in vitro. GnRH-a and
      hCG triggering inversely modulated PEDF mRNA and protein level in human granulosa
      cells in vivo. In the GnRH-a triggering mouse model, we showed similar increase
      in PEDF to VEGF ratio as in the in vitro results. OHSS-predisposed mice did not
      develop OHSS parameters after GnRH-a triggering, opposed to hCG-triggered mice.
      Finally, GnRH-a triggering of OHSS-predisposed mice significantly increased
      ovarian PEDF to VEGF ratio compared with hCG-triggered mice and control mice.
      CONCLUSIONS: GnRH-a triggering induces a direct effect on PEDF/VEGF balance in
      granulosa cells inversely to hCG. Our results suggest a novel elucidation to the
      GnRH-a triggering-mediated risk reduction of OHSS and may clarify the pros and
      cons of this triggering method.

PMID- 26308291
TI  - Impact of the Macronutrient Composition of a Nutritional Supplement on Muscle
      Protein Synthesis Rates in Older Men: A Randomized, Double Blind, Controlled
      Trial.
AB  - CONTEXT: An impaired muscle protein synthetic response to feeding likely
      contributes to muscle loss with aging. There are few data available on the effect
      of the macronutrient composition of clinical supplements on the postprandial
      muscle protein synthetic response in older subjects. OBJECTIVE: The objective of
      the study was to determine the impact of the macronutrient composition of a
      nutritional supplement on the postprandial muscle protein synthetic response in
      older men. METHODS: A total of 45 nonsarcopenic older men (aged 69 +/- 1 y; body
      mass index 25.7 +/- 0.3 kg/m(2)) were randomly assigned to ingest 21 g of leucine
      enriched whey protein with carbohydrate (9 g) and fat (3 g) (Pro-En), an
      isonitrogenous amount of 21 g of leucine-enriched whey protein without
      carbohydrate and fat (Pro), or an isocaloric mixture (628 kJ) containing
      carbohydrate and fat only (En). Stable isotope tracer methodology was applied to
      assess the basal as well as the postprandial muscle protein synthesis rates in
      the three groups. RESULTS: Ingestion of protein in the Pro-En and Pro groups
      significantly increased muscle protein synthesis rates when compared with the
      basal rates (from 0.032 +/- 0.003%/h to 0.05%/h 3 +/- 0.004%/h and 0.040%/h +/-
      0.003%/h to 0.049%/h +/- 0.003%/h, respectively; P < .05), whereas ingestion of
      carbohydrate and fat did not increase muscle protein synthesis rates in the En
      group (from 0.039%/h +/- 0.004%/h to 0.040%/h +/- 0.003%/h; P = .60). Despite the
      greater postprandial rise in circulating insulin concentration in the Pro-En
      group, no significant differences were observed in postprandial muscle protein
      synthesis rates between the Pro-En and Pro groups (P = .32). Postprandial muscle
      protein synthesis rates were higher in the Pro-En vs En group (P = .01).
      CONCLUSION: The ingestion of a nutritional supplement containing 21 g of leucine
      enriched whey protein significantly raises muscle protein synthesis rates in
      nonsarcopenic older men, but coingestion of carbohydrate and fat does not
      modulate the postprandial muscle protein synthetic response to protein ingestion
      in older men.

PMID- 26308292
TI  - Serum Uric Acid Levels and Risk of Metabolic Syndrome: A Dose-Response Meta
      Analysis of Prospective Studies.
AB  - CONTEXT: An excess circulating uric acid level, even within the normal range, is
      always comorbid with metabolic syndrome (MS), several of its components, and
      nonalcoholic fatty liver disease (NAFLD), which was regarded as hepatic
      manifestation of MS; however, these associations remain controversial. OBJECTIVE:
      This study aimed to quantitatively assess the relationship between the serum uric
      acid (SUA) levels and the MS/NAFLD risk. DESIGN: We searched for related
      prospective cohort studies including SUA as an exposure and MS/NAFLD as a result
      in MEDLINE (PubMed) and EMBASE databases up to January 31, 2015 and July 28,
      2015, respectively. Pooled relative risks (RRs) and corresponding 95% confidence
      intervals (CIs) were extracted. A random-effects model was used to evaluate dose
      response relationships. MAIN OUTCOMES: On the basis of 11 studies (54 970
      participants and 8719 MS cases), a combined RR of 1.72 (95% CI, 1.45-2.03; P <
      .0001) was observed for the highest SUA level category compared with the lowest
      SUA level category. Furthermore, based on nine studies (51 249 participants and
      8265 MS cases), dose-response analysis suggested that each 1 mg/dL SUA increment
      was roughly linearly associated with the MS risk (RR, 1.30; 95% CI, 1.22-1.38; P
      < .0001). Beyond that, SUA level increased NAFLD risk (RR, 1.46; 95% CI, 1.31
      1.63). Each 1 mg/dL SUA level increment led to 21% increase in the NAFLD risk.
      CONCLUSIONS: This meta-analysis suggests that higher SUA levels led to an
      increased risk of MS regardless of the study characteristics, and were consistent
      with a linear dose-response relationship. In addition, SUA was also a causal
      factor for the NAFLD risk.

PMID- 26308293
TI  - Ethnic Differences in the Role of Adipocytokines Linking Abdominal Adiposity and
      Insulin Sensitivity Among Asians.
AB  - CONTEXT: Among Asian ethnic groups, Chinese or Malays are more insulin sensitive
      than South Asians, in particular in lean individuals. We have further reported
      that body fat partitioning did not explain this ethnic difference in insulin
      sensitivity. OBJECTIVE: We examined whether adipocytokines might explain the
      ethnic differences in the relationship between obesity and insulin resistance
      among the three major ethnic groups in Singapore. DESIGN AND PARTICIPANTS: This
      was a cross-sectional study of 101 Chinese, 82 Malays, and 81 South Asian men.
      Insulin sensitivity index (ISI) was measured using hyperinsulinemic euglycemic
      clamp. Visceral (VAT) and subcutaneous adipose tissue (SAT) volumes were
      quantified using magnetic resonance imaging. MAIN OUTCOME MEASURES: Plasma total
      and high-molecular-weight adiponectin, leptin, visfatin, apelin, IL-6, fibroblast
      growth factor 21 (FGF21), retinol binding protein-4 (RBP 4), and resistin were
      measured using enzyme-linked immunoassays. RESULTS: Principle component (PC)
      analysis on the adipocytokines identified three PCs, which explained 49.5% of the
      total variance. Adiponectin loaded negatively, and leptin and FGF21 loaded
      positively onto PC1. Visfatin, resistin, and apelin all loaded positively onto
      PC2. IL-6 loaded positively and RBP-4 negatively onto PC3. Only PC1 was
      negatively associated with ISI in all ethnic groups. In the path analysis, SAT
      and VAT were negatively associated with ISI in Chinese and Malays without
      significant mediatory role of PC1. In South Asians, the relationship between VAT
      and ISI was mediated partly through PC1, whereas the relationship between SAT and
      ISI was mediated mainly through PC1. CONCLUSIONS: The relationships between
      abdominal obesity, adipocytokines and insulin sensitivity differ between ethnic
      groups. Adiponectin, leptin, and FGF21 play a mediating role in the relationship
      between abdominal adiposity and insulin resistance in South Asians, but not in
      Malays or Chinese.

PMID- 26308294
TI  - Glucocorticoid Excess Increases Hepatic 11beta-HSD-1 Activity in Humans:
      Implications in Steroid-Induced Diabetes.
AB  - CONTEXT: Animal studies indicate that glucocorticoids increase hepatic 11beta
      hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) expression and activity.
      OBJECTIVE: Our goal was to determine whether glucocorticoid excess increases
      cortisol production in the liver via 11beta-HSD-1 enzyme pathway in humans.
      DESIGN: A total of 1 mg each [4-(13)C] cortisone and [9,12,12-(2)H3] cortisol
      were ingested, and [1,2,6,7-(3)H] cortisol was infused to measure C13 cortisol
      (derived from ingested [4-(13)C] cortisone) turnover using the triple tracer
      technique, whereas glucose turnover was measured using isotope dilution technique
      following [6-6(2)H2] glucose infusion during a saline clamp. SETTING: This study
      took place at the Mayo Clinic Clinical Research Unit. PARTICIPANTS: Thirty
      nondiabetic healthy subjects participated. INTERVENTION: Subjects were randomized
      to hydrocortisone (n = 15) or placebo 50 mg twice daily (n = 15) for 1 week.
      OUTCOME MEASURES: Hepatic cortisol production and endogenous glucose production
      were measured. RESULTS: Plasma cortisol concentrations were higher throughout the
      study period in hydrocortisone group. Rates of appearance of C13 cortisol and
      hepatic C13 cortisol production were higher in hydrocortisone vs placebo group,
      indicating increased hepatic 11beta-HSD-1 activity. Higher plasma cortisol and
      presumably higher intrahepatic cortisol was associated with impaired suppression
      of endogenous glucose production in hydrocortisone vs placebo group. CONCLUSION:
      Chronic glucocorticoid excess increases intrahepatic cortisone to cortisol
      conversion via the 11beta-HSD-1 pathway. The extent to which this causes or
      exacerbates steroid induced hepatic insulin resistance remains to be determined.

PMID- 26308296
TI  - An Overview of the Current Status of Organ Donation and Transplantation in
      Brazil.

PMID- 26308295
TI  - Short-Term Safety of Zoledronic Acid in Young Patients With Bone Disorders: An
      Extensive Institutional Experience.
AB  - CONTEXT: Zoledronic acid (ZA) is increasingly used in young patients with bone
      disorders. However, data related to the safety of ZA administration in this
      population are limited. OBJECTIVE: The study aimed to characterize the short-term
      safety profile of ZA and identify risk factors for ZA-related adverse events
      (AEs) in young patients. DESIGN, SETTING, AND PARTICIPANTS: This was a
      retrospective chart review of inpatients and outpatients less than 21 years old
      who received at least one ZA infusion between July 2010 and January 2014 at The
      Children's Hospital of Philadelphia. RESULTS: Eighty-one patients (56% male;
      median age, 12 y; age at first infusion, 0.5 to 20 y) with diverse skeletal
      disorders received a total of 204 infusions. The most common indications were
      osteoporosis (33% of cohort) and osteogenesis imperfecta (27.2%). The median ZA
      dose was 0.025 mg/kg (interquartile range, 0.025-0.05); the median dosing
      interval was 6 months (range, 1 to 25.6 mo). AEs were mild and more common after
      the first ZA infusion in patients with no previous bisphosphonate exposure:
      hypophosphatemia (25.2% of infusions), acute phase reactions (19.1%), and
      hypocalcemia (16.4%). Symptomatic hypocalcemia requiring iv calcium occurred
      after two infusions. ZA dose was significantly associated with hypophosphatemia,
      but not other AEs. Hypocalcemia was more common in patients with high bone
      turnover as assessed by preinfusion alkaline phosphatase levels. AEs were not
      associated with diagnosis, baseline serum calcium, or calcium/calcitriol
      supplementation. CONCLUSION: Acute AEs related to ZA infusion in youths are
      common, occur principally after the first ZA infusion in bisphosphonate-naive
      patients, and are typically mild and easily managed. Future prospective studies
      are needed to determine the potential long-term risks, as well as benefits, of ZA
      therapy in the pediatric population.

PMID- 26308298
TI  - Distal Airway Stem Cells are Essential for Lung Regeneration.

PMID- 26308299
TI  - Pharmacovigilance in Europe.

PMID- 26308300
TI  - Randall E. Morris, MD, FRCP: Stanford University School of Medicine and former
      Global Head of Transplantation Therapeutic Area (Discovery Research) and Global
      Head of Transplantation Translational Medicine, Novartis, AG, Basel, Switzerland.

PMID- 26308302
TI  - Outcome of Extracorporeal Membrane Oxygenation as a Bridge To Lung
      Transplantation: An Institutional Experience and Literature Review.
AB  - BACKGROUND: Extracorporeal life support (ECLS) as a bridge to lung
      transplantation (LuTx) is a promising option for patients with end-stage lung
      disease on the transplant waiting list. We investigated the outcome of patients
      bridged to lung transplantation on ECLS technologies, mainly extracorporeal
      membrane oxygenation (ECMO). METHODS: Between January 2007 and October 2013, ECLS
      was implanted in 30 patients with intention to bridge to LuTx. Twenty-six
      patients (26/30) were successfully bridged to LuTx on ECLS. The most common
      diagnosis was cystic fibrosis (N = 12). Venovenous ECMO was used in 10,
      venoarterial in 4, interventional lung assist in 5, and stepwise combination of
      them in 7 recipients. RESULTS: Two patients weaned from ECMO, and 2 patients died
      on ECMO on the waiting list. Median duration of ECLS was 21 days (1-81 years).
      Six patients were awake and spontaneously breathing during ECLS support. Thirty
      day, 1-year, and 2-year survivals were 89%, 68%, and 53%, respectively, for
      bridged patients and 96%, 85%, and 79%, respectively, for control group (P =
      0.001). Three months conditional survivals were 89% and 69% at 1 and 2 years for
      ECLS group, compared to 92% and 86% for control group (P = 0.03). Cystic fibrosis
      recipients had 82% survival rate at 1 and 2 years. All recipients bridged to LuTx
      on awake ECLS (N = 6) are alive with a median follow-up of 10.8 months (range, 6
      21 months). CONCLUSIONS: Our data show significantly lower survival in this high
      risk group compared to patients transplanted without preoperative ECLS. Awake and
      ambulatory ECLS provides the best prognosis for these high-risk patients.

PMID- 26308303
TI  - The Ups and Downs of TORKinibs in Transplantation.

PMID- 26308304
TI  - Kidneys from Older Living Donors Provide Excellent Short and Intermediate
      Outcomes--A Single China Center's Experience.
AB  - BACKGROUND: Transplantation with kidneys from older living donors is on the rise,
      yet controversy still exists over whether the outcomes are as satisfactory as
      with kidneys from younger donors. METHODS: We retrospectively analyzed 1009
      living donor kidney transplants performed at our center between 2006 and 2013.
      Graft and patient outcomes were compared between transplants with kidneys from
      old living donors (OLD, 55-65 years) (n = 264) and from young living donors (YLD,
      <55 years) (n = 745). RESULTS: The age was 32.80 +/- 9.71 years and 33.91 +/-
      5.98 years for recipient in YLD and OLD group, respectively. Death-censored graft
      survival at 1, 3, and 5 years was 98.8%, 97.1%, and 95.8% in patients receiving
      YLD kidneys, similar to the corresponding values of 97.6%, 95.5% and 95.5% in
      patients receiving OLD kidneys (P = 0.356). Patient survival at 1, 3, and 5 years
      after transplantation was also similar for patients receiving YLD kidneys (98.5%,
      97.1%, and 96.7%) and for patients receiving OLD kidneys (99.6%, 99.6%, and
      96.8%; P = 0.110). The OLD kidneys were not associated with increased risk of
      death-censored graft failure (hazard ratio, 2.5; 95% confidence interval, 0.57 to
      11.11) and patient death (hazard ratio, 1.67; 95% confidence interval, 0.75 to
      3.73). In addition, there is no increased graft loss or patient death for each 10
      year increase in donor age. Transplantation with OLD kidneys was not associated
      with reduced patient or graft outcomes in the short term (<= 12 months) or medium
      term (>1 year). CONCLUSIONS: Graft and patient outcomes after living-donor kidney
      transplantation are similar in the short-term and medium-term for donors aged 55
      to 65 years and for younger donors. Therefore, the use of OLD kidneys should be
      encouraged in China.

PMID- 26308305
TI  - Pediatric Prevention and Intervention in the Community.
AB  - The health of children is largely influenced by the factors in their immediate
      environment, including their families, schools, and neighborhoods. However,
      according to Bronfenbrenner's ecological systems theory, children are also
      influenced by larger social systems that indirectly effect development, like the
      school system and the cultural values and traditions of the larger society. This
      issue of the Journal of Prevention and Intervention in the Community highlights
      research that investigates the importance of the various ecological systems on
      child health. Three articles focus on issues with particular relevance in
      pediatrics, including tobacco prevention, injury prevention, and sexually
      transmitted infection treatment. Two articles focus on community-engaged
      intervention programs to treat chronic childhood issues. Finally, one article
      focuses on the interaction between culture and pediatric health beliefs. 

PMID- 26308306
TI  - The Impact of a Community-Based Activity and Nutrition Program for Children.
AB  - There is consensus that community-wide integration of programs targeting
      pediatric obesity prevention is needed. The present article describes the growth,
      acceptability, and impact of a school- and community-based kids' marathon program
      targeting physical activity and nutrition. Youth in the program are encouraged to
      incrementally walk/run/jog a marathon and improve their diet through nutrition
      challenges. Participants track mileage and healthy eating over approximately 6
      months, and complete a final marathon mile at the program's culminating event.
      Across 21 schools, 404 students between kindergarten and 8th grade reported on
      their experiences in the program. Also, 19 school coordinators rated their
      perceptions of the program's impact. While the data is preliminary and
      retrospective, it indicates that participants are highly engaged and that the
      program has potential to improve physical activity and other healthy lifestyle
      behaviors in many children. Strengths of the program, implications for obesity
      prevention, and future directions are also discussed. 

PMID- 26308307
TI  - The Association of Parental Self-Efficacy and Parent-Youth Connectedness With
      Youth Smoking Intentions.
AB  - Little attention has been paid to understanding how parents of differing
      race/ethnicity perceive their effectiveness in exercising anti-smoking parenting
      practices and how these behaviors affect youth's smoking intentions. We explored
      the association of parent-youth connectedness and parental self-efficacy and
      youths' smoking intentions in a group of African American and Caucasian never
      smokers. Based on Social Bonding Theory and Social Learning Theory, a
      questionnaire was administered to nonsmoking, 9-16-year-old youth and parent
      dyads, assessing youth smoking intentions and parental measures of connectedness
      and self-efficacy. Youth risk factors for intending to smoke were increased
      parent-youth conflict and protective factors were increased parental monitoring,
      increased parental rule setting, and higher parental self-efficacy. Parent-youth
      connectedness and parental self-efficacy did not differ by parental smoking
      status or by race/ethnicity. Our findings underscore the importance of strong
      parenting practices and parental self-efficacy in protecting against youth
      intention to smoke and these may be important to target in future interventions. 

PMID- 26308308
TI  - The Use of Focus Groups to Mobilize a High-Risk Community in an Effort to Prevent
      Injuries.
AB  - Youth involved in supervised activities and provided with safe play areas during
      high-risk times will sustain fewer injuries. This qualitative focus group study
      of community organizations, parents, and youth in a high-risk community
      demonstrated barriers to participation in and resources available for after
      school programs, as well as components of an ideal after-school program.
      Community organizations believed pooling resources and holding programs in
      centralized locations, such as schools, would make programs more affordable and
      overcome transportation barriers. Parent and youth also preferred to hold
      activities in schools; however, parents were concerned with the cost of programs
      and times they were offered, while students were more concerned with age
      appropriate, safe programs that prohibited "bullies" from participating. Specific
      suggested program contents were similar between parents and youth. Information
      gathered from the focus groups had significant implications for program and
      resource development in the targeted community. 

PMID- 26308309
TI  - Parental Health Attributions of Childhood Health and Illness: Development of the
      Pediatric Cultural Health Attributions Questionnaire (Pedi-CHAQ).
AB  - The causes attributed to childhood health and illness across cultures (cultural
      health attributions) are key factors that are now more frequently identified as
      affecting the health outcomes of children. Research suggests that the causes
      attributed to an event such as illness are thought to affect subsequent
      motivation, emotional response, decision making, and behavior. To date, there is
      no measure of health attributions appropriate for use with parents of pediatric
      patients. Using the Many-Facets approach to Rasch analysis, this study assesses
      the psychometrics of a newly developed instrument, the Pediatric Health
      Attributions Questionnaire (Pedi-CHAQ), a measure designed to assess the cultural
      health attributions of parents in diverse communities. Results suggest acceptable
      Rasch model statistics of fit and reliability for the Pedi-CHAQ. A shortened
      version of the questionnaire was developed as a result of this study and next
      steps are discussed. 

PMID- 26308310
TI  - Adolescent Sexually Transmitted Infections: A Community Epidemic.
AB  - Women under 25 years of age have higher rates of sexually transmitted infections
      (STIs) than other populations. Providing follow-up for adolescents with an STI is
      especially challenging in emergency departments (EDs). In our ED, we discovered
      that a significant number of adolescents with an STI did not receive adequate
      treatment, and 25% of those with an STI who were treated remained unaware of
      their infection. These deviations from ideal care are problematic because
      adolescents with untreated STIs are at risk for pelvic inflammatory disease and
      infertility. Those who were treated but unaware of their infection are unable to
      take steps to avoid re-infection, including partner treatment. We hypothesized
      that an improved system to handle STI test results would reduce the burden on ED
      staff and increase the proportion of adolescents receiving appropriate follow-up.
      This intervention has the potential to significantly address the STI epidemic in
      our community. 

PMID- 26308311
TI  - Engaging Patients With Sickle Cell Disease and Their Families in Disease
      Education, Research, and Community Awareness.
AB  - This article describes the planning, implementation, and evaluation of Research
      and Education Day, an event designed to promote education and awareness of sickle
      cell disease (SCD), while also fostering and increasing participation by families
      in research studies. Quantitative and qualitative evaluation data (tracking of
      participant attendance and participation in research studies; program evaluation
      surveys) indicate that program goals were achieved. Results show that event
      attendance, research participation and retention, and community volunteerism has
      increased exponentially over the 8-year history of the event. Parents report that
      their top-rated reasons for attending are learning about research studies and
      participating in SCD-related educational activities. Data also show that families
      learn about the event in multiple ways (i.e., flyers, clinic staff, word of
      mouth, etc.). Research and Education Day is a model for educating participants
      with sickle cell and their families, engaging them in research studies, and
      enhancing community awareness and support. 

PMID- 26308312
TI  - Cyproheptadine Use in Children With Functional Gastrointestinal Disorders.
AB  - OBJECTIVE: The objective of this study was to evaluate clinical improvement and
      safety with use of cyproheptadine in functional gastrointestinal disorders
      (FGIDs) in children. METHODS: Retrospectively evaluating the efficacy and safety
      of the use for indications including Rome III-defined FGIDs: functional abdominal
      pain, functional dyspepsia, irritable bowel syndrome (IBS), abdominal migraine,
      cyclic vomiting syndrome. Response categories were as follows: no improvement
      group/partial improvement group; requiring intervention, or complete improvement
      group (CIG); warranting discontinuation; ongoing use; or parental unwillingness
      to stop medication. RESULTS: Among 307 patients, 151 included; 58% girls, ages 1
      to 18 years (median 9); 110 (72.8%) reported complete symptom improvement; 41
      (27.2%) reported no or partial improvement. Mean initial and final doses in the
      CIG were 4.85 mg/day (0.14 mg . kg . day) and 5.34 mg/day (0.14 mg . kg . day),
      respectively. A total of 102/151 (68%) reported no adverse effects. Adverse
      effects shown were as sleepiness in 19/151 (13%) and weight gain in 15/151 (10%).
      Cyproheptadine was effective in improving symptoms of functional abdominal pain,
      functional dyspepsia, in a relatively larger number of patients. Patients in
      smaller numbers had significant improvement 13/18 (72%) abdominal migraine, 10/10
      (100%) IBS, and 6/8 (75%) cyclic vomiting syndrome. This is the first time report
      of improvement in IBS. Other pharmacodynamics had been as follows: the lower the
      body weight, the higher are the odds of no to partial improvement; patients in no
      improvement group/partial improvement group experience more adverse effects as
      compared to the CIG; the single best predictor of clinical improvement was body
      mass index. A 1 unit increase in body mass index with cyproheptadine use
      increased the odds of clinical improvement by 1.5-fold (P = 0.01). CONCLUSIONS:
      Cyproheptadine effectively improves symptoms of Rome III-defined FGIDs and has a
      good safety profile when used for these indications.

PMID- 26308313
TI  - Gallbladder and Pancreas in Henoch-Schonlein Purpura: Review of the Literature.
AB  - OBJECTIVE: Involvement of the pancreato-biliary system has been occasionally
      noted in Henoch-Schonlein purpura. Furthermore, cases of this vasculitis syndrome
      sometimes develop in the context of a viral hepatitis or after hepatitis
      vaccination. METHODS: We completed a review of the literature. RESULTS: Fifty
      reports published between 1977 and 2015 were retained for the analysis. A
      pancreato-biliary involvement was recognized in 34 individually well-described
      patients (?:? = 19:15) with severe abdominal pain: pancreatitis (N = 20),
      acalculous cholecystitis (N = 11), both pancreatitis and cholecystitis (N = 3).
      In all of the pancreatitis patients, full recovery occurred (within <=3 weeks in
      three-fourths of the patients). Cholecystectomy was performed in 8 cholecystitis
      patients. Seventeen Henoch-Schonlein patients (?:? = 9:8) were associated with a
      viral liver disease and 4 (?:? = 1:3) with a hepatitis vaccination. The
      vasculitis syndrome rapidly remitted in the 7 patients accompanying hepatitis A
      or E, in 2 patients of hepatitis B, and in the 4 patients preceded by a
      vaccination. Henoch-Schonlein purpura seemed to be serious in 5 patients with
      chronic hepatitis B and in 3 with chronic hepatitis C. CONCLUSIONS: This analysis
      indicates that pancreato-biliary involvement is unusual in Henoch-Schonlein
      purpura. This complication deserves consideration in patients with especially
      severe abdominal pain. Finally, viral hepatitides and hepatitis vaccinations seem
      to be rare triggers of Henoch-Schonlein purpura.

PMID- 26308314
TI  - Timing of Cholecystectomy in Children With Biliary Pancreatitis.
AB  - BACKGROUND: Biliary pancreatitis (BP) is common in adults and children. Current
      standard of care is to perform a cholecystectomy (CCE) to decrease the recurrence
      risk of pancreatitis. Controversy exists as to the timing of surgery, early
      versus delayed surgical intervention. Adult literature suggests a greater benefit
      of early CCE. Comparatively, there is limited pediatric literature as to the
      optimal timing of a CCE in children. We report a retrospective case series of
      children with BP who underwent early versus late CCE. METHODS: A retrospective
      chart review was performed of children with BP for a period of 45 months.
      Reviewed information included patient demographics, timing of CCE, and the
      occurrence of adverse events preceding or following surgical intervention. Early
      CCE was defined as surgery during the index admission; late CCE was defined as
      surgery during a subsequent admission. RESULTS: Nineteen children and adolescents
      (17 girls) were identified to have had BP with a subsequent CCE. Cholecystectomy
      was performed early in 9 patients with no adverse events. Ten patients had
      delayed surgery with 4 occurrences of adverse clinical events (recurrence of
      pancreatitis or biliary colic abdominal pain) while awaiting their CCE.
      CONCLUSIONS: Adverse biliary-related events occur at a higher rate in children
      with mild BP who undergo a delayed CCE when compared to early CCE performance.
      Early CCE is safe to perform in children with mild BP.

PMID- 26308315
TI  - Eosinophilic Esophagitis.

PMID- 26308316
TI  - Prevalence of Peripheral Eosinophilia at Diagnosis in Children With Inflammatory
      Bowel Disease.
AB  - BACKGROUND AND OBJECTIVE: Inflammatory bowel disease (IBD) encompasses 2
      disorders of unknown etiology: Crohn disease (CD) and ulcerative colitis (UC).
      There has been a continuous search for markers for disease activity. Eosinophils
      are granulocytic leukocytes that are implicated in the pathogenesis of IBD. The
      aim of this study was to examine the prevalence and significance of peripheral
      eosinophilia (PE) at diagnosis in children with IBD. METHODS: A comprehensive
      chart review of all children with diagnosed as having IBD between January 2006
      and August 2014 was performed. Patients with PE at diagnosis were compared with
      those without in relation to disease clinical activity and disease course.
      RESULTS: A total of 109 children (mean age 14.6 +/- 2.77, range 4.5-17.9 years,
      55 boys) with IBD (68 with CD and 41 with UC) who were studied for a mean
      duration of 2.82 +/- 1.89 (range 0.1-9.2 years) were identified. At diagnosis, 44
      (40.4%) children had PE, which was more prevalent in patients with UC compared
      with those with CD (61.3% vs 36.3%, P < 0.05). At diagnosis, PE was more common
      in patients with high eosinophilic count in colonic biopsy samples (P < 0.01) and
      was significantly associated with disease activity as indicated by Pediatric CD
      Activity Index for children with CD (P < 0.05), Pediatric UC Activity Index for
      children with UC (P < 0.01). CONCLUSIONS: PE is a common finding at diagnosis in
      children with IBD especially in those with UC. Patients with PE at diagnosis are
      more likely to present with higher clinical activity indices. PE is associated
      with more eosinophils in colonic biopsy samples.

PMID- 26308317
TI  - Prevalence and Health Outcomes of Functional Gastrointestinal Symptoms in Infants
      From Birth to 12 Months of Age.
AB  - OBJECTIVES: The aim of the study was to review published evidence and the opinion
      of practising clinicians on the prevalence and long-term health consequences of
      functional gastrointestinal symptoms in infants younger than 12 months. METHODS:
      PubMed was searched from inception to November 2014 to find articles reporting
      the prevalence and long-term health outcomes of infantile colic, regurgitation,
      functional constipation, functional diarrhoea, and dyschezia in infants younger
      than <12 months. A questionnaire was sent to practising clinicians worldwide, and
      a group of 15 international experts met to discuss the likely frequency and
      longer-term consequences of these symptoms. RESULTS: The literature search
      identified 30 studies reporting the prevalence of infantile colic (2%-73%), 13
      that of regurgitation (3%-87%), 8 that of functional constipation (0.05%-39.3%),
      2 that of functional diarrhoea (2%-4.1%), and 3 that of dyschezia (0.9%-5.6%).
      The studies varied in design, populations investigated, and definition of the
      symptoms. Questionnaires were received from 369 respondents. The experts agreed
      that the likely prevalences for colic, regurgitation, and functional constipation
      were 20%, 30%, and 15%, respectively. The limited data in the literature for
      functional diarrhoea and dyschezia suggest prevalences <10%. Infantile colic may
      be associated with future health problems in a subset of infants. CONCLUSIONS:
      Functional gastrointestinal symptoms appear to occur in a significant proportion
      of infants younger than 12 months and may have an impact on future health
      outcomes. Prospective collection of data according to agreed criteria is needed
      to obtain more accurate estimates of the prevalence and consequences of these
      symptoms.

PMID- 26308319
TI  - Development and Validation of a Rome III Functional Gastrointestinal Disorders
      Questionnaire for Infants and Toddlers.
AB  - OBJECTIVE: Functional gastrointestinal disorders (FGIDs) in infants and toddlers
      are common, but no questionnaire is available for use in clinic and research. The
      purpose of the present study was to develop and validate a questionnaire
      assessing symptoms associated with FGIDs in infants and toddlers. METHODS:
      Questions were developed based on the Rome III diagnostic criteria for FGIDs. A
      group of parents of children with FGIDs and experts in FGID reviewed the
      questionnaire for content, understandability, and completeness (face validity).
      Initial content validity was established by comparing physician and questionnaire
      diagnoses in a group of 332 consecutive new patients at a tertiary care clinic.
      RESULTS: Ten parents and 8 experts identified no major problems, indicating good
      face validity. Of 332 consecutive new patients, age 1 month to 4 year of age, 172
      subjects (52% of the sample) qualified for a FGID by parent responses to the
      questionnaire (mean age = 1.23 year, 53% girls). All of these subjects also
      received an FGID diagnosis by their physician. Agreement between parent and
      doctor was fair to substantial (kappa = 0.18-0.76), except for infant rumination
      and functional diarrhea in infants, which showed poor overlap. CONCLUSIONS: The
      newly developed Rome III questionnaire for infants and toddlers had good initial
      face and content validity. This questionnaire will be an important addition to
      clinical care and research of infant/toddler FGIDs. Replication of these findings
      in primary care is needed.

PMID- 26308320
TI  - Insufficient Body Weight of Adults Born With Esophageal Atresia.
AB  - OBJECTIVES: Impaired growth has been reported in children born with esophageal
      atresia (EA). Their nutritional fate at adulthood remains uncertain though. Our
      objectives were to determine the body mass index (BMI) of adult patients with EA
      followed up from 2009 to 2011 in the EA clinic of a university-affiliated
      hospital in Quebec (Canada), and investigate characteristics associated with
      underweight. METHODS: The 40 adult patients with EA attending the clinic were
      invited to participate. Height and weight were measured and BMI calculated.
      Patients with BMI < 18.5 kg/m were deemed underweight. Patients' characteristics
      were obtained, including digestive symptoms and compensatory eating behaviors.
      Nonparametric tests were used to compare the proportion of underweight among
      patients with EA with that found in the Quebec population and the characteristics
      between patients with EA deemed underweight and those with BMI >= 18.5 kg/m.
      RESULTS: The final sample included 16 women and 21 men, ages 18 to 44 years. Mean
      BMI was 21.3 +/- 4.9 kg/m and 24.3% had BMI < 18.5 kg/m, which is higher than in
      the Quebec adult population (2.5%, P < 0.001). Compared with patients with EA
      having BMI >= 18.5 kg/m, underweight patients had more often experienced failure
      to thrive during their adolescence (55.6% vs 7.4%, P = 0.006), and reported
      severe postprandial fullness (62.5% vs 21.4%, P = 0.040), the need to eat slowly
      (87.5% vs 46.4%; P = 0.045), and severe difficulties to swallow dry solid foods
      (50.0% vs 14.3%, P = 0.054). CONCLUSIONS: Insufficient body weight is prevalent
      in this sample of adult patients with EA and could result from digestive
      symptoms. Follow-up with a gastroenterologist and nutritional counseling should
      be considered for adult patients with EA.

PMID- 26308321
TI  - Need for Infant Formula.

PMID- 26308322
TI  - Symptom Association: An Imperfect Pairing.

PMID- 26308323
TI  - History of Pediatric Endoscopy: An American Perspective, Part I.

PMID- 26308318
TI  - Microbiome-Epigenome Interactions and the Environmental Origins of Inflammatory
      Bowel Diseases.
AB  - The incidence of pediatric inflammatory bowel disease (IBD), which includes Crohn
      disease and ulcerative colitis, has risen alarmingly in the Western and
      developing world in recent decades. Epidemiologic (including monozygotic twin and
      migrant) studies highlight the substantial role of environment and nutrition in
      IBD etiology. Here we review the literature supporting the developmental and
      environmental origins hypothesis of IBD. We also provide a detailed exploration
      of how the human microbiome and epigenome (primarily through DNA methylation) may
      be important elements in the developmental origins of IBD in both children and
      adults. 

PMID- 26308324
TI  - History of Pediatric Endoscopy: An American Perspective Part II.

PMID- 26308325
TI  - Author's Response.

PMID- 26308326
TI  - Asymmetric Evolutionary Games.
AB  - Evolutionary game theory is a powerful framework for studying evolution in
      populations of interacting individuals. A common assumption in evolutionary game
      theory is that interactions are symmetric, which means that the players are
      distinguished by only their strategies. In nature, however, the microscopic
      interactions between players are nearly always asymmetric due to environmental
      effects, differing baseline characteristics, and other possible sources of
      heterogeneity. To model these phenomena, we introduce into evolutionary game
      theory two broad classes of asymmetric interactions: ecological and genotypic.
      Ecological asymmetry results from variation in the environments of the players,
      while genotypic asymmetry is a consequence of the players having differing
      baseline genotypes. We develop a theory of these forms of asymmetry for games in
      structured populations and use the classical social dilemmas, the Prisoner's
      Dilemma and the Snowdrift Game, for illustrations. Interestingly, asymmetric
      games reveal essential differences between models of genetic evolution based on
      reproduction and models of cultural evolution based on imitation that are not
      apparent in symmetric games. 

PMID- 26308327
TI  - Drug Effects and Clinical Investigations for Contrast-Induced Nephropathy After
      Coronary Angiography or Percutaneous Coronary Intervention in Patients With
      Diabetes.
AB  - The aim of the study was to investigate the risk factors of preprocedural
      laboratory investigations and drug effects to the incidence of contrast-induced
      nephropathy (CIN) in patients with diabetes who underwent coronary angiography or
      percutaneous coronary intervention and to assess the short-term safety. We
      retrospectively studied a total of 568 patients with diabetes who underwent
      coronary angiography or percutaneous coronary intervention from January, 2013 to
      January, 2014 in our hospital and compared the baseline clinical characteristics,
      especially the laboratory investigations and preprocedural drugs of those 2
      groups (with CIN group and without CIN group), and half year follow-up. Overall,
      53 (9.33%) patients were developed into CIN according to the definition of an
      increase of 25% from the baseline of serum creatinine concentration, supposing
      that on the basis of an increase of 44.2 MUmol/L, the incidence would be 0.88%
      (5/568). No significant differences were found between the 2 groups with respect
      to age, diabetes mellitus duration, operation type, contrast type and volume,
      left ventricular ejection fraction, and combined diseases including hypertension,
      myocardial infarction, Arrhythmia, etc. However, patients with CIN tended to be
      lighter in body weight (P = 0.027) and were more often female [odds ratio (OR) =
      2.8, P < 0.01], and also had a higher prevalence with acute coronary syndrome (OR
      = 5.1, P < 0.01). On the contrary to most studies, the preprocedural serum
      creatinine in with CIN group in our study was lower than without CIN group (P <
      0.001). As for the preprocedural drugs, statins seemed could decrease the
      incidence of CIN (OR = 0.34, P < 0.05), and the use of diuretics might increase
      the occurrence of CIN (OR = 2.62, P < 0.05). As regard to the follow-up results,
      the hospitalization days and expense of with CIN group were significantly longer
      and higher than the without CIN group, but no significance was found between
      rehospitalization rate in half year. Preprocedural preventions are essential
      because there is no effective treatment for CIN our findings could be considered
      in clinical practice. There are many risk factors for CIN; it is necessary to
      distinguish the high-risk patients so as to carry out corresponding protection
      actions.

PMID- 26308328
TI  - Effects of Narrow Band Ultraviolet B on Serum Levels of Vascular Endothelial
      Growth Factor and Interleukin-8 in Patients with Psoriasis.
AB  - The aim of this study was to investigate the effects of narrow band ultraviolet B
      (NB-UVB) therapy on serum levels of vascular endothelial growth factor (VEGF) and
      interleukin-8 (IL-8) in patients with psoriasis. Relevant Chinese and English
      scientific literature databases were searched to identify studies published
      before November, 2013 that included serum VEGF and IL-8 levels in patients with
      psoriasis. The studies retrieved from database searches were screened on the
      basis of predefined selection criteria, and data from finally selected studies
      were extracted for meta-analysis. Analyses were conducted using STATA 12.0
      software. Our systematic search resulted in retrieval of 700 studies (500 studies
      in Chinese, 200 studies in English), and after a multistep screening process, 13
      studies met the inclusion criteria and were enrolled for meta-analysis. The 13
      studies contained a combined total of 400 patients with psoriasis and 221 healthy
      controls. The results of meta-analysis revealed that healthy controls exhibited
      significantly lower serum level of VEGF, compared to patients with psoriasis
      before therapy. After NB-UVB, VEGF levels were significantly decreased in
      patients with psoriasis, as compared to their pretherapy VEGF levels. Although no
      statistically significant differences were detected in IL-8 serum levels between
      patients with psoriasis and healthy controls before therapy, after NB-UVB
      therapy, the serum IL-8 levels in patients with psoriasis were markedly
      decreased. Corresponding reductions in the psoriasis area and severity index
      scores of patients with psoriasis were observed after NB-UVB treatment. Our
      results revealed that NB-UVB therapy significantly decreased the serum levels of
      VEGF and IL-8 in patients with psoriasis. Furthermore, VEGF and IL-8 levels
      correlated with disease status, indicating that they are sensitive biomarkers for
      evaluating the effectiveness of psoriasis therapy. 

PMID- 26308329
TI  - In-utero exposures and the evolving epidemiology of paediatric allergy.
AB  - PURPOSE OF REVIEW: Emerging evidence suggests that the rising prevalence of early
      onset 'noncommunicable' diseases, such as paediatric atopy, is related to modern
      environmental changes, the effects of which appear to commence in utero or even
      preconception. Here, we review how recent publications have contributed further
      to our understanding of the influence of in-utero exposures on the predisposition
      to immune dysregulation, with a particular focus on the evolving epidemiology of
      paediatric allergy. RECENT FINDINGS: New evidence suggests that inter-individual
      variations in immune function development are principally driven by nonheritable
      factors, for example periconceptional environment. One of the most significant
      influences is maternal nutrition during pregnancy. New studies further support a
      healthy balanced maternal diet that contains immunomodulatory nutrients,
      prebiotics and probiotics, which benefit multiple aspects of fetal development,
      including immune development. In addition, declining maternal biodiversity,
      maternal stress and exposures to environmental pollutants further interact to
      have adverse influences on the developing immune system. SUMMARY: The in-utero
      period appears to be a critical time point. Further investigations of gene
      environmental interaction mechanisms are essential prior to further
      recommendations of early-life preventive strategies to reduce the growing global
      burden of allergic disease, as well as other 'noncommunicable' diseases.

PMID- 26308330
TI  - The genes and the environment in nasal allergy.
AB  - PURPOSE OF REVIEW: In this review, we summarize the latest publications on the
      genetic and environmental determinants of allergic rhinitis. RECENT FINDINGS:
      Recent advances in genetic technology and bioinformatics have enabled
      simultaneous unbiased analysis of the entire genome regarding DNA sequence
      variants, epigenetic modifications and gene expression, providing functional
      correlates for DNA variants and phenotypes. As a result, new genes of
      mitochondrial and B-lymphocyte metabolism have been associated with allergic
      rhinitis phenotypes. Epidemiological studies recently showed an increased risk to
      develop allergic rhinitis in all age groups with reduction in farm exposure and
      in children with few older siblings. Climate changes seem to have also influenced
      pollen exposure and pollen-induced allergic disease. Lastly, occupational
      rhinitis has been increasingly recognized as a large burden to society. SUMMARY:
      In summary, new high throughput genetics research technologies have pointed to
      new previously unsuspected pathways that may modulate the risk of developing
      allergic rhinitis such as mitochondrial metabolism. In addition, recent
      environmental factors found to influence the risk of developing allergic rhinitis
      include exposure to farm, pollution, occupational agents, and changes in climate.

PMID- 26308331
TI  - Current novel approaches in systemic therapy of atopic dermatitis: specific
      inhibition of cutaneous Th2 polarized inflammation and itch.
AB  - PURPOSE OF REVIEW: This present review gives an overview on different approaches
      on systemic treatment of atopic dermatitis with a focus on molecules that are
      presently investigated as defined target structures in clinical studies with
      patients with atopic dermatitis. RECENT FINDINGS: Available systemic drugs for
      the treatment of atopic dermatitis are limited. There is a high need for the
      development of new treatment regimen. Current studies address novel biologicals
      or small molecules for the treatment of atopic dermatitis. In particular,
      interventions in the T-helper 2 cell (Th2) allergic inflammation are promising.
      Dupilumab, a humanized monoclonal antibody to the interteukin-4R is the first
      antibody (i.e. 'biological') with published efficacy shown in controlled
      prospective studies in atopic dermatitis. A number of other target molecules is
      currently addressed in clinical studies with blocking antibodies against target
      molecules of Th2 polarized inflammation in atopic dermatitis (e.g. interleukins
      13, 22, 31, thymic stromal lymphopoetin). Inhibiting phospodiesterase-4,
      chemoattractant receptor-homologous molecule 2, the histamine-4 receptor, or the
      neurokine-1 receptor may lead to the approval of novel 'small drugs' for a
      specific treatment of atopic dermatitis. Antifungals may be helpful in the
      variant of head and neck dermatitis associated with sensitizations against
      Malassezia species. Induction of specific immune tolerance (e.g. with allergen
      specific immunotherapy) should be further studied in terms of the management of
      atopic dermatitis because available clinical studies resulted in inconsistent
      results on the skin condition. SUMMARY: Current studies with new substances for
      the systemic treatment of atopic dermatitis have tremendous implications for the
      future management of atopic dermatitis.

PMID- 26308332
TI  - Methylisothiazolinone outbreak in the European Union.
AB  - PURPOSE OF REVIEW: The aim of this review was to examine the current outbreak of
      cases of contact allergy to methylisothiazolinone in Europe, a phenomenon that
      has also been observed worldwide, despite initial legislative control of the
      introduction of methylisothiazolinone into the market. RECENT FINDINGS: Reported
      allergic contact reactions are primarily eczematous, most commonly in women over
      40 from cosmetic use, but there are reports of noneczematous eruptions such as
      lichen planus-like or lymphomatoid reactions. Methylisothiazolinone in cosmetic,
      personal care, for example, wet wipe, and household products are the most common
      exposure. Occupational exposure is represented by workplace use of hygiene
      (healthcare) and beauty products (hairdressers, beauticians) together with water
      based paints and other aqueous solutions such as cutting
      fluid.Methylisothiazolinone should be patch tested at a concentration of 2000 ppm
      (0.2% aqueous) to maximize sensitivity of the test.Notwithstanding the
      recommendation to discontinue the use of methylisothiazolinone in leave-on
      cosmetics, studies suggest safer use of concentrations should also be determined
      for rinse-off products. Legislation to improve labelling of industrial materials
      is also required.Going forward there is a need for collaboration between the
      cosmetic industry and interested physicians to break the recurrent cycle of
      sensitization to preservatives as one is replaced with another to maintain the
      risk of sensitization at an acceptably low level. SUMMARY: Methylisothiazolinone
      is particularly relevant at present as strategies to control the outbreak are yet
      to be enforced and there is no current evidence of the outbreak abating.

PMID- 26308334
TI  - The Genetic Structure of Marijuana and Hemp.
AB  - Despite its cultivation as a source of food, fibre and medicine, and its global
      status as the most used illicit drug, the genus Cannabis has an inconclusive
      taxonomic organization and evolutionary history. Drug types of Cannabis
      (marijuana), which contain high amounts of the psychoactive cannabinoid Delta9
      tetrahydrocannabinol (THC), are used for medical purposes and as a recreational
      drug. Hemp types are grown for the production of seed and fibre, and contain low
      amounts of THC. Two species or gene pools (C. sativa and C. indica) are widely
      used in describing the pedigree or appearance of cultivated Cannabis plants.
      Using 14,031 single-nucleotide polymorphisms (SNPs) genotyped in 81 marijuana and
      43 hemp samples, we show that marijuana and hemp are significantly differentiated
      at a genome-wide level, demonstrating that the distinction between these
      populations is not limited to genes underlying THC production. We find a moderate
      correlation between the genetic structure of marijuana strains and their reported
      C. sativa and C. indica ancestry and show that marijuana strain names often do
      not reflect a meaningful genetic identity. We also provide evidence that hemp is
      genetically more similar to C. indica type marijuana than to C. sativa strains. 

PMID- 26308335
TI  - The Uptake of Prevention of Mother-to-Child HIV Transmission Programs in China: A
      Systematic Review and Meta-Analysis.
AB  - BACKGROUND: No systematic review of prevention of mother to child transmission
      (PMTCT) in China has been performed. We aimed to estimate the uptake of PMTCT
      programs services in China. METHODS: We searched MEDLINE, EMBASE, Cochrane
      Central Register of Controlled Trials, China National Knowledge Infrastructure,
      Chinese Biomedical Literature Database, and Wanfang (Chinese) to identify
      research studies. Only descriptive epidemiological studies were eligible for this
      study. RESULTS: A total of 57 eligible cross-section studies were finally
      included. We estimated that the mean HIV-positive rate of exposed infants was
      4.4% (95% CI = 3.2-5.5), and more than 33% of exposed infants had not undergone
      HIV diagnostic testing. The percentage of initiating antiretroviral therapy (ART)
      in HIV-positive women was 71.0% (95% CI = 66.3-75.8), and that for initiating
      antiretroviral prophylaxis (ARP) in exposed infants was 78.3% (95% CI = 74.9
      81.8); also, 31.3% (95% CI = 15.5-47.0) of women with HIV and < 1% of exposed
      infants received the combination of three antiretroviral drugs. There were bigger
      gap of uptake of PMTCT programs between income levels, and cities with a low
      income level had a higher percentage of initiating ART in HIV-positive women
      (80%) and ARP in exposed infants (85%) compared to cities with high-middle income
      (57% and 65%, respectively) (P<0.05). CONCLUSIONS: This paper highlights the need
      to further scale up PMTCT services in China, especially in regions with the
      lowest coverage, so that more women can access and utilize them. However, some
      estimated outcome should be interpreted with caution due to the high level of
      heterogeneity and the small number of studies.

PMID- 26308336
TI  - Development and Evaluation of the Brief Sexual Openness Scale-A Construal Level
      Theory Based Approach.
AB  - Obtaining reliable and valid data on sensitive questions represents a
      longstanding challenge for public health, particularly HIV research. To overcome
      the challenge, we assessed a construal level theory (CLT)-based novel method. The
      method was previously established and pilot-tested using the Brief Sexual
      Openness Scale (BSOS). This scale consists of five items assessing attitudes
      toward premarital sex, multiple sexual partners, homosexuality, extramarital sex,
      and commercial sex, all rated on a standard 5-point Likert scale. In addition to
      self-assessment, the participants were asked to assess rural residents, urban
      residents, and foreigners. The self-assessment plus the assessment of the three
      other groups were all used as subconstructs of one latent construct: sexual
      openness. The method was validated with data from 1,132 rural-to-urban migrants
      (mean age = 32.5, SD = 7.9; 49.6% female) recruited in China. Consistent with
      CLT, the Cronbach alpha of the BSOS as a conventional tool increased with social
      distance, from .81 for self-assessment to .97 for assessing foreigners. In
      addition to a satisfactory fit of the data to a one-factor model (CFI = .94, TLI
      = .93, RMSEA = .08), a common factor was separated from the four perspective
      factors (i.e., migrants' self-perspective and their perspectives of rural
      residents, urban residents and foreigners) through a trifactor modeling analysis
      (CFI = .95, TLI = .94, RMSEA = .08). Relative to its conventional form, CTL-based
      BSOS was more reliable (alpha: .96 vs .81) and valid in predicting sexual desire,
      frequency of dating, age of first sex, multiple sexual partners and STD history.
      This novel technique can be used to assess sexual openness, and possibly other
      sensitive questions among Chinese domestic migrants. 

PMID- 26308337
TI  - Effective Stimulus Parameters for Directed Locomotion in Madagascar Hissing
      Cockroach Biobot.
AB  - Swarms of insects instrumented with wireless electronic backpacks have previously
      been proposed for potential use in search and rescue operations. Before deploying
      such biobot swarms, an effective long-term neural-electric stimulus interface
      must be established, and the locomotion response to various stimuli quantified.
      To this end, we studied a variety of pulse types (mono- vs. bipolar; voltage- vs.
      current-controlled) and shapes (amplitude, frequency, duration) to parameters
      that are most effective for evoking locomotion along a desired path in the
      Madagascar hissing cockroach (G. portentosa) in response to antennal and cercal
      stimulation. We identified bipolar, 2 V, 50 Hz, 0.5 s voltage controlled pulses
      as being optimal for evoking forward motion and turns in the expected
      contraversive direction without habituation in ~50% of test subjects, a
      substantial increase over ~10% success rates previously reported. Larger
      amplitudes for voltage (1-4 V) and current (50-150 MUA) pulses generally evoked
      larger forward walking (15.6-25.6 cm; 3.9-5.6 cm/s) but smaller concomitant
      turning responses (149 to 80.0 deg; 62.8 to 41.2 deg/s). Thus, the radius of
      curvature of the initial turn-then-run locomotor response (~10-25 cm) could be
      controlled in a graded manner by varying the stimulus amplitude. These findings
      could be used to help optimize stimulus protocols for swarms of cockroach biobots
      navigating unknown terrain. 

PMID- 26308338
TI  - Correction: Comparative Anatomy of the Bony Labyrinth (Inner Ear) of Placental
      Mammals.

PMID- 26308339
TI  - Design of a Vitronectin-Based Recombinant Protein as a Defined Substrate for
      Differentiation of Human Pluripotent Stem Cells into Hepatocyte-Like Cells.
AB  - Maintenance and differentiation of human pluripotent stem cells (hPSCs) usually
      requires culture on a substrate for cell adhesion. A commonly used substratum is
      Matrigel purified from Engelbreth-Holm-Swarm sarcoma cells, and consists of a
      complex mixture of extracellular matrix proteins, proteoglycans, and growth
      factors. Several studies have successfully induced differentiation of hepatocyte
      like cells from hPSCs. However, most of these studies have used Matrigel as a
      cell adhesion substrate, which is not a defined culture condition. In an attempt
      to generate a substratum that supports undifferentiated properties and
      differentiation into hepatic lineage cells, we designed novel substrates
      consisting of vitronectin fragments fused to the IgG Fc domain. hPSCs adhered to
      these substrates via interactions between integrins and the RGD (Arg-Gly-Asp)
      motif, and the cells maintained their undifferentiated phenotypes. Using a
      previously established differentiation protocol, hPSCs were efficiently
      differentiated into mesendodermal and hepatic lineage cells on a vitronectin
      fragment-containing substrate. We found that full-length vitronectin did not
      support stable cell adhesion during the specification stage. Furthermore, the
      vitronectin fragment with the minimal RGD-containing domain was sufficient for
      differentiation of human induced pluripotent stem cells into hepatic lineage
      cells under completely defined conditions that facilitate the clinical
      application of cells differentiated from hPSCs. 

PMID- 26308340
TI  - Assessment of Fibrinolysis in Sepsis Patients with Urokinase Modified
      Thromboelastography.
AB  - INTRODUCTION: Impairment of fibrinolysis during sepsis is associated with worse
      outcome. Early identification of this condition could be of interest. The aim of
      this study was to evaluate whether a modified point-of-care viscoelastic
      hemostatic assay can detect sepsis-induced impairment of fibrinolysis and to
      correlate impaired fibrinolysis with morbidity and mortality. METHODS: This
      single center observational prospective pilot study was performed in an adult
      Intensive Care Unit (ICU) of a tertiary academic hospital. Forty consecutive
      patients admitted to the ICU with severe sepsis or septic shock were included.
      Forty healthy individuals served as controls. We modified conventional kaolin
      activated thromboelastography (TEG) adding urokinase to improve assessment of
      fibrinolysis in real time (UK-TEG). TEG, UK-TEG, plasminogen activator inhibitor
      (PAI)-1, thrombin-activatable fibrinolysis inhibitor (TAFI), d-dimer, DIC scores
      and morbidity (rated with the SOFA score) were measured upon ICU admission.
      Logistic regression was used to calculate odds ratios (ORs) and 95% confidence
      intervals (95% CIs) of mortality at ICU discharge. RESULTS: UK-TEG revealed a
      greater impairment of fibrinolysis in sepsis patients compared to healthy
      individuals confirmed by PAI-1. TAFI was not different between sepsis patients
      and healthy individuals. 18/40 sepsis patients had fibrinolysis impaired
      according to UK-TEG and showed higher SOFA score (8 (6-13) vs 5 (4-7), p = 0.03),
      higher mortality (39% vs 5%, p = 0.01) and greater markers of cellular damage
      (lactate levels, LDH and bilirubin). Mortality at ICU discharge was predicted by
      the degree of fibrinolysis impairment measured by UK-TEG Ly30 (%) parameter (OR
      0.95, 95% CI 0.93-0.98, p = 0.003). CONCLUSIONS: Sepsis-induced impairment of
      fibrinolysis detected at UK-TEG was associated with increased markers of cellular
      damage, morbidity and mortality.

PMID- 26308342
TI  - OPTICAL COHERENCE TOMOGRAPHY IN JUVENILE NEURONAL CEROID LIPOFUSCINOSIS.
AB  - PURPOSE: To report optical coherence tomography findings obtained in two patients
      with juvenile neuronal ceroid lipofuscinosis. METHODS: Two case reports. RESULTS:
      Two 7-year-old girls presented with decreased visual acuity, clumsiness, night
      blindness, and behavioral problems. Optical coherence tomography showed an
      overall reduction in thickness of the central retina, as well as the outer and
      the inner retinal layers. The degenerative retinal changes were the same, despite
      different mutations in the CLN3 gene. CONCLUSION: In these rare cases of juvenile
      neuronal ceroid lipofuscinosis, optical coherence tomography enabled unambiguous
      detection of prominent morphologic abnormalities of the retina at the patient's
      first presentation. The advanced stage of photoreceptor degeneration seen in our
      patients shows that a diagnosis can potentially be made much earlier.

PMID- 26308341
TI  - The Effects of Sex Hormonal Fluctuations during Menstrual Cycle on Cortical
      Excitability and Manual Dexterity (a Pilot Study).
AB  - AIM: To investigate whether hormonal fluctuations during the menstrual cycle
      affect corticospinal excitability, intracortical inhibition (ICI) or facilitation
      (ICF) in primary motor cortex, and also whether the hormonal fluctuations have
      any effect on manual dexterity in neurologically intact women. MATERIALS AND
      METHODS: Twenty volunteers (10 Female, 10 Male) were included in this study. The
      levels of progesterone and estradiol were measured from saliva during the women's
      menstrual follicular, ovulation and mid-luteal phases. Motor evoked potentials
      were recorded from the right first dorsal interosseous muscle. Single and paired
      pulse Transcranial Magnetic Stimulation (TMS) were delivered in a block of 20
      stimuli. With paired-pulse technique, 3ms and 10ms inter-stimulus intervals were
      used to assess ICI and ICF, respectively. The Grooved Pegboard Test (GPT) was
      completed in each session before the TMS assessments. Male participants were
      tested at similar time intervals as female participants. RESULTS: Mixed design
      ANOVA revealed that GPT score in female participants was significantly lower at
      the mid-luteal phase compared to the ovulation phase (p = 0.017). However, it was
      not correlated with progesterone or estrogen fluctuations during the menstrual
      cycle. The results also showed that the effect of phase, sex and the interaction
      of phase by sex for resting motor threshold, ICI or ICF were not significant (p >
      0.05). CONCLUSION: Manual dexterity performance fluctuates during the menstrual
      cycle in neurologically intact women, which might be due to the balance of the
      neuromodulatory effects of P4 and E2 in the motor cortex during different phases.

PMID- 26308343
TI  - Finite Verb Morphology in the Spontaneous Speech of Dutch-Speaking Children With
      Hearing Loss.
AB  - OBJECTIVE: In this study, the acquisition of Dutch finite verb morphology is
      investigated in children with cochlear implants (CIs) with profound hearing loss
      and in children with hearing aids (HAs) with moderate to severe hearing loss.
      Comparing these two groups of children increases our insight into how hearing
      experience and audibility affect the acquisition of morphosyntax. DESIGN:
      Spontaneous speech samples were analyzed of 48 children with CIs and 29 children
      with HAs, ages 4 to 7 years. These language samples were analyzed by means of
      standardized language analysis involving mean length of utterance, the number of
      finite verbs produced, and target-like subject-verb agreement. The outcomes were
      interpreted relative to expectations based on the performance of typically
      developing peers with normal hearing. Outcomes of all measures were correlated
      with hearing level in the group of HA users and age at implantation in the group
      of CI users. RESULTS: For both groups, the number of finite verbs that were
      produced in 50-utterance sample was on par with mean length of utterance and at
      the lower bound of the normal distribution. No significant differences were found
      between children with CIs and HAs on any of the measures under investigation.
      Yet, both groups produced more subject-verb agreement errors than are to be
      expected for typically developing hearing peers. No significant correlation was
      found between the hearing level of the children and the relevant measures of verb
      morphology, both with respect to the overall number of verbs that were used and
      the number of errors that children made. Within the group of CI users, the
      outcomes were significantly correlated with age at implantation. CONCLUSION: When
      producing finite verb morphology, profoundly deaf children wearing CIs perform
      similarly to their peers with moderate-to-severe hearing loss wearing HAs.
      Hearing loss negatively affects the acquisition of subject-verb agreement
      regardless of the hearing device (CI or HA) that the child is wearing. The
      results are of importance for speech-language pathologists who are working with
      children with a hearing impairment indicating the need to focus on subject-verb
      agreement in speech-language therapy.

PMID- 26308344
TI  - Molecular Dynamics Investigation of gluazo, a Photo-Switchable Ligand for the
      Glutamate Receptor GluK2.
AB  - Photochromic ligands (PCLs), defined as photoswitchable molecules that are able
      to endow native receptors with a sensitivity towards light, have become a
      promising photopharmacological tool for various applications in biology. In
      general, PCLs consist of a ligand of the target receptor covalently linked to an
      azobenzene, which can be reversibly switched between two configurations upon
      light illumination. Gluazo, as a PCL that targets excitatory amino acid
      receptors, in its dark-adapted trans iso-form was characterized to be a partial
      agonist of the kainate glutamate receptor GluK2. Application of UV light leads to
      the formation of the cis form, with remarkedly reduced affinity towards GluK2.
      The mechanism of the change of ligand affinity induced by the photoisomerization
      was unresolved. The presented computational study explains how the isomerization
      of such a PCL affects the structural changes in the target receptor that lead to
      its activation. 

PMID- 26308345
TI  - Implementation of Point-of-Care Diagnostics Leads to Variable Uptake of Syphilis,
      Anemia and CD4+ T-Cell Count Testing in Rural Maternal and Child Health Clinics.
AB  - INTRODUCTION: Anemia, syphilis and HIV are high burden diseases among pregnant
      women in sub-Saharan Africa. A quasi-experimental study was conducted in four
      health facilities in Southern Mozambique to evaluate the effect of point-of-care
      technologies for hemoglobin quantification, syphilis testing and CD4+ T-cell
      enumeration performed within maternal and child health services on testing and
      treatment coverage, and assessing acceptability by health workers. METHODS:
      Demographic and testing data on women attending first antenatal care services
      were extracted from existing records, before (2011; n = 865) and after (2012; n =
      808) introduction of point-of-care testing. Study outcomes per health facility
      were compared using z-tests (categorical variables) and Wilcoxon rank-sum test
      (continuous variables), while inverse variance weights were used to adjust for
      possible cluster effects in the pooled analysis. A structured acceptability
      assessment interview was conducted with health workers before (n = 22) and after
      (n = 19). RESULTS: After implementation of point-of-care testing, there was no
      significant change in uptake of overall hemoglobin screening (67.9% to 83.0%; p =
      0.229), syphilis screening (80.8% to 87.0%; p = 0.282) and CD4+ T-cell testing
      (84.9% to 83.5%; p = 0.930). Initiation of antiretroviral therapy for treatment
      eligible women was similar in the weighted analysis before and after, with
      variability among the sites. Time from HIV diagnosis to treatment initiation
      decreased (median of 44 days to 17 days; p<0.0001). A generally good
      acceptability for point-of-care testing was seen among health workers.
      CONCLUSIONS: Point-of-care CD4+ T-cell enumeration resulted in a decreased time
      to initiation of antiretroviral therapy among treatment eligible women, without
      significant increase in testing coverage. Overall hemoglobin and syphilis
      screening increased. Despite the perception that point-of-care technologies
      increase access to health services, the variability in results indicate the
      potential for detrimental effects in some settings. Local context needs to be
      considered and services restructured to accommodate innovative technologies in
      order to improve service delivery to expectant mothers.

PMID- 26308346
TI  - Increasing Nucleosome Occupancy Is Correlated with an Increasing Mutation Rate so
      Long as DNA Repair Machinery Is Intact.
AB  - Deciphering the multitude of epigenomic and genomic factors that influence the
      mutation rate is an area of great interest in modern biology. Recently, chromatin
      has been shown to play a part in this process. To elucidate this relationship
      further, we integrated our own ultra-deep sequenced human nucleosomal DNA data
      set with a host of published human genomic and cancer genomic data sets. Our
      results revealed, that differences in nucleosome occupancy are associated with
      changes in base-specific mutation rates. Increasing nucleosome occupancy is
      associated with an increasing transition to transversion ratio and an increased
      germline mutation rate within the human genome. Additionally, cancer single
      nucleotide variants and microindels are enriched within nucleosomes and both the
      coding and non-coding cancer mutation rate increases with increasing nucleosome
      occupancy. There is an enrichment of cancer indels at the theoretical start (74
      bp) and end (115 bp) of linker DNA between two nucleosomes. We then hypothesized
      that increasing nucleosome occupancy decreases access to DNA by DNA repair
      machinery and could account for the increasing mutation rate. Such a relationship
      should not exist in DNA repair knockouts, and we thus repeated our analysis in
      DNA repair machinery knockouts to test our hypothesis. Indeed, our results
      revealed no correlation between increasing nucleosome occupancy and increasing
      mutation rate in DNA repair knockouts. Our findings emphasize the linkage of the
      genome and epigenome through the nucleosome whose properties can affect genome
      evolution and genetic aberrations such as cancer. 

PMID- 26308347
TI  - Characteristics of Patients With Early-Onset Arthritis in Latin America:
      Description of the REPANARC Cohort.
AB  - BACKGROUND: While many studies have tried to show that early intervention
      improves the clinical outcomes of early-onset arthritis, only a few were carried
      out in Latin America. OBJECTIVES: The aim of this study was to describe the Pan
      American Registry of Early-Onset Arthritis (REPANARC) project and report the
      preliminary outcomes of a cohort of patients. METHODS: The REPANARC cohort
      consisted of a sample of patients from 6 Latin American countries. Patients with
      arthritis of 1 or more joints of 1-year duration or less were assessed by a
      rheumatologist during 6 consecutive clinical visits for a follow-up period of 2
      years. The registry included clinical characteristics, medical history, physical
      examination, disease activity, analytical chemistries, imaging, current
      treatment, and a set of patient-reported outcome measures evaluating disability,
      psychological distress, and quality of life. RESULTS: A total of 173 patients
      were included with mean age of 41.9 +/- 13.2 years; 83.8% were women. The
      predominant presentations at onset were insidious, polyarticular, additive,
      bilateral, and symmetrical. The initial diagnoses were rheumatoid arthritis
      (50.6%), undifferentiated arthritis (40.5%), and other arthritis (8.9%). With
      Disease Activity Score in 28 Joints, 76.9% had moderate to high disease activity,
      and 61.9% had moderate to severe disability (Health Assessment Questionnaire).
      Considering undifferentiated arthritis, 60.3% persisted undifferentiated, 29.4%
      evolved as rheumatoid arthritis, 4.4% remained self-limited, and 5.9% to other
      forms. The frequencies of depression and anxiety were high as measured with the
      Hospital Anxiety and Depression Scale, and approximately 20% had significant
      decrements in quality of life measured with the Medical Outcomes Study Short-Form
      36 Health Survey Version 2. Mean time from the first symptoms to the first visit
      to a rheumatologist was 126 days. Shorter delays were confirmed to be associated
      with better outcomes. CONCLUSIONS: The REPANARC project is a useful tool to
      provide valuable information regarding patients with early-onset arthritis
      attending rheumatology centers in Latin-America.

PMID- 26308348
TI  - Fibromyalgia and Obesity: The Association Between Body Mass Index and Disability,
      Depression, History of Abuse, Medications, and Comorbidities.
AB  - AIM: The aim of this study was to determine the frequency of increasing body mass
      index (BMI) in fibromyalgia (FM) and to understand the impact of increasing BMI
      on FM. METHODS: Patients with FM were divided into 3 BMI classifications: normal
      weight, overweight, and obese. We then sought relationships of increasing BMI to
      core process FM variables and symptoms and disability, as well as medical
      comorbidities and demographic, socioeconomic, psychiatric, and treatment data.
      RESULTS: Of 224 patients, 0.4% were underweight; 25.9%, normal weight; 29.9%,
      overweight; 43.8%, obese. We found no differences within groups with regard to
      age, gender, demographics, FM symptoms, FM impact questionnaire scores, and
      meeting the American College of Rheumatology 1990 criteria and FM survey
      criteria. Patients with FM who are obese, compared with normal-weight patients,
      have higher depression scores measured by Patient Health Questionnaire 9 (13.2
      [6.6] vs 10.5 [6], P = 0.03), report increased disability by Health Assessment
      Questionnaire Disability Index scores (1.3 [0.6] vs 0.9 [0.6], P < 0.001),
      exercise less (8.4% vs 25.4%, P = 0.003), have more medical comorbidities (1.5
      [1.3] vs 0.7 [0.9], P < 0.001), take more medications for FM (3.5 [2.2] vs 2.1
      [1.8], P < 0.001), and report higher prevalence of abuse (48% vs 33.9%, P =
      0.016) and sexual abuse (17.3% vs 6.8%, P = 0.01). CONCLUSIONS: Compared with
      normal-weight patients, obese FM patients are more disabled, report more medical
      comorbidities, exercise less, have a higher incidence of abuse, report increased
      depressive symptoms, and take more medications for FM. Bivariate analysis showed
      association of increasing BMI with the Health Assessment Questionnaire Disability
      Index (not FM impact questionnaire) and depression. We confirm that the
      prevalence of overweight and obesity is high in FM and believe that physicians
      treating FM should be aware of our bivariate linear correlations and discuss
      weight loss with their FM patients. Even if increasing BMI is not intrinsic to
      FM, it contributes to poor mood and functional outcome and should be a treatment
      goal.

PMID- 26308349
TI  - Routine Assessment of Patient Index Data (RAPID3) and Bath Ankylosing Spondylitis
      Disease Activity Index (BASDAI) Scores Yield Similar Information in 85 Korean
      Patients With Ankylosing Spondylitis Seen in Usual Clinical Care.
AB  - BACKGROUND: Disease-specific ankylosing spondylitis (AS) indices, including
      BASDAI (Bath AS Disease Activity Index), BASFI (Bath AS Functional Index), ASDAS
      (AS Disease Activity Score), and BASMI (Bath AS Metrology Index), are widely used
      in clinical trials and in some clinical settings, but not in most routine care.
      Laboratory tests usually are the only quantitative measures included in routine
      care of AS patients, but often are poorly informative. Routine Assessment of
      Patient Index Data 3 (RAPID3) on a Multidimensional Health Assessment
      Questionnaire (MDHAQ) is feasible and informative in many rheumatic diseases.
      OBJECTIVE: The aim of this study was to compare RAPID3 to BASDAI, BASFI, ASDAS,
      and BASMI in a cross-sectional analysis of 85 Korean AS patients collected in
      routine care. METHODS: MDHAQ/RAPID3, BASDAI, and BASFI were completed by
      patients, and ASDAS and BASMI assessed by health professionals. Indices and
      individual measures were compared using correlations, cross tabulations, scatter
      plots, and kappa statistics. RESULTS: RAPID3 scores were correlated significantly
      with BASDAI (rho = 0.82) and ASDAS-ESR (erythrocyte sedimentation rate) (rho =
      0.76), at levels similar to the correlation of BASDAI with ASDAS-ESR (rho =
      0.81). All 21 patients with BASDAI scores of 4 or greater, indicating active AS,
      were among 39 patients who had RAPID3 scores of greater than 12, indicating high
      severity, whereas 79% of 33 patients with ASDAS of greater than 1.3, indicating
      high activity, had RAPID3 high severity. CONCLUSIONS: RAPID3 gives similar
      information to BASDAI and ASDAS in AS patients, in this limited cross-sectional
      study from 1 setting. Ankylosing spondylitis-specific measures are needed for
      clinical trials, but poorly feasible in most busy clinical settings. The
      MDHAQ/RAPID3 offers pragmatic quantitative clinical assessment of AS patients in
      routine care.

PMID- 26308350
TI  - Systematic Review of Diffuse Alveolar Hemorrhage in Systemic Lupus Erythematosus:
      Focus on Outcome and Therapy.
AB  - BACKGROUND: Diffuse alveolar hemorrhage (DAH) is an uncommon but potentially life
      threatening manifestation of systemic lupus erythematosus (SLE) associated with
      high mortality. Although survival and its associated clinical, laboratory, and
      therapeutic features have been reported for case reports and series, they have
      not been systematically reviewed. OBJECTIVES: The purpose of this systematic
      review was to assess survival of episodes of DAH in SLE over 3 decades and to
      categorize trends in therapies, commonly utilized to treat this disorder.
      RESULTS: Overall, SLE patients survived 61% of 174 DAH episodes representing 140
      patients. Episode survival was 67% in the time period from 2000 to 2013.
      Corticosteroids were nearly universally used therapeutically, and
      cyclophosphamide was used in 55%. Plasmapheresis was used in 31% and did not
      appear to be associated with survival. CONCLUSIONS: Diffuse alveolar hemorrhage
      in SLE still carries a high risk of mortality; however, survival trends appear to
      demonstrate an increase from approximately 25% in the 1980s to 67% in the current
      decade. Increased use of cyclophosphamide appears to be associated with better
      survival, whereas plasmapheresis does not appear to influence outcome. Although
      these results need to be interpreted with caution because they are not derived
      from randomized controlled trials, we believe this represents the largest
      reported compilation of survival data in DAH associated with SLE.

PMID- 26308351
TI  - Lingual Infarction in a Child With Systemic Lupus Erythematosus.

PMID- 26308352
TI  - Septic Sacroiliitis Following Corticosteroid Injection in a Patient Under Anti
      Tumor Necrosis Factor Therapy.

PMID- 26308354
TI  - Pregnancy Does Not Adversely Affect Postoperative Pain and Function in Women With
      Total Hip Arthroplasty.

PMID- 26308355
TI  - Extrapulmonary Tuberculosis Infection in Mexican Patients With Idiopathic
      Inflammatory Myopathies.

PMID- 26308356
TI  - Antimicrobial and Antileishmanial Activities of Diterpenoids Isolated from the
      Roots of Salvia deserta.
AB  - Four diterpenes with biological activity were isolated from Salvia deserta roots.
      Taxodione was considered leishmanicidal with an IC50 value of 1.46 uM (0.46 mg/L)
      against Leishmania donovani and also exhibited antifungal and antimicrobial
      activities. Ferruginol displayed the greatest activity [24-h IC50 of 4.5 uM (1.29
      mg/L)] against the fish pathogenic bacteria Streptococcus iniae. The crude
      extract fraction that contained the isolated compounds 7-O-acetylhorminone and
      horminone showed stronger in vitro antibacterial activity (1.3 mg/L for
      Staphylococcus aureus and 1.1 mg/L for methicillin-resistant S. aureus) than the
      compounds tested alone. 7-O-Acetylhorminone and horminone exhibited a synergistic
      effect against methicillin-resistant S. aureus (FIC of 0.2), and horminone had
      better activity against S. aureus with respect to other compounds isolated from
      S. deserta roots. In larvicidal bioassays, these extracts and isolated pure
      compounds did not show any activity at the highest dose of 125 mg/L against 1-d
      old Aedes aegypti larvae.

PMID- 26308357
TI  - Antinociceptive and Anti-inflammatory Activities of the Methanolic Extract from
      the Stem Bark of Lophanthera lactescens.
AB  - Lophanthera lactescens is a medicinal plant commonly used in traditional medicine
      to relieve fever and pain in inflammatory processes. In the present study, the in
      vivo antinociceptive and anti-inflammatory effects of the methanolic extract from
      L. lactescens have been investigated. Antinociceptive activity was evaluated
      through writhing, formalin, and tail flick tests, while the anti-inflammatory
      activity was evaluated through paw oedema and air pouch tests in mice. A
      phytochemical analysis was performed. The extract produced significant inhibition
      on nociception induced by acetic acid-induced abdominal writhing, formalin, and
      tail flick tests, and on inflammation induced by oedema and air pouch tests. The
      previous administration of atropine and glibenclamide reduced the antinociceptive
      effect produced by the methanolic extract from L. lactescens on the tail flick
      test in 89% and 66%, respectively. The methanolic extract had no significant
      effect in the open field test. No intoxication symptoms were observed in the
      animals administered orally at increasing doses up to 2000 mg/kg. The methanolic
      extract from the stem bark of L. lactescens possesses antinociceptive properties
      on models of acute pain induced by chemical and thermal stimuli as well as in
      models of inflammation and further suggests that this anti-inflammatory activity
      might involve inhibition of the proinflammatory cytokines, and the
      antinociceptive activity might involve participation of the cholinergic system
      and adenosine triphosphate-dependent K+ channel.

PMID- 26308358
TI  - Pheophorbide a from Capsosiphon fulvescens Inhibits Advanced Glycation End
      Products Mediated Endothelial Dysfunction.
AB  - During hyperglycemia, the first step toward the formation of advanced glycation
      end products is the nonenzymatic glycation between the carbonyl group of a sugar
      and the primary amino group of a protein. Advanced glycation end products are
      then produced through more complex reactions. Reactive oxygen species derived
      from advanced glycation end products may play a key role in inflammation of the
      endothelium, leading to the complications seen in diabetes. Glycolaldehyde
      induced advanced glycation end products have been reported to express
      proinflammatory cytokines, such as tumor necrosis factor-alpha and interleukin
      1beta. This study focused on Capsosiphon fulvescens, a Capsosiphonaceae type of
      green algae that has shown potential as a functional food material. Pheophorbide
      a, an anti-glycation compound, was isolated from C. fulvescens by extraction
      using a mixture of ethanol and water, followed by column fractionation of the
      resulting extract. The compound separated from C. fulvescens was identified by
      means of high-performance liquid chromatography combined with mass spectrometry.
      Pheophorbide a showed scavenging activity of the intracellular reactive oxygen
      species as well as monocyte adhesiveness inhibitory activity on the human
      myelomonocytic cell line (THP-1) and human umbilical vein endothelial cells
      cocultivation system. The mRNA levels of inflammation-related genes such as
      monocyte chemoattractant protein-1 and interleukin-6 were significantly decreased
      by pheophorbide a, and advanced glycation end products-stimulated tumor necrosis
      factor-alpha and interleukin-1beta were downregulated as well. These results
      indicate that pheophorbide a has significant reactive oxygen species-scavenging
      activity, monocyte adhesive inhibitory activity, and downregulatory activity of
      cytokines related to inflammation affecting the endothelium. Pheophorbide a could
      therefore be a promising candidate for modulating endothelial cell dysfunction. 

PMID- 26308359
TI  - Diterpenoids from the Whole Plant of Lagochilus platyacanthus.
AB  - Five new diterpenoids, lagoditerpenes A-E (1-3, 5, 6), along with ten known
      compounds were isolated from the herb of Lagochilus platyacanthus. The absolute
      structures of 1-4 and 6 were unequivocally elucidated by extensive spectroscopic
      analyses in association with single-crystal X-ray diffraction, in which compounds
      1 and 2 were the epimers at C-13. Furthermore, in in vitro assays, compounds 1, 2
      and 6 showed moderate hemostatic activities by shortening the values of activated
      partial thromboplastin time. 

PMID- 26308360
TI  - Evolution of Vertebrate Adam Genes; Duplication of Testicular Adams from Ancient
      Adam9/9-like Loci.
AB  - Members of the disintegrin metalloproteinase (ADAM) family have important
      functions in regulating cell-cell and cell-matrix interactions as well as cell
      signaling. There are two major types of ADAMs: the somatic ADAMs (sADAMs) that
      have a significant presence in somatic tissues, and the testicular ADAMs (tADAMs)
      that are expressed predominantly in the testis. Genes encoding tADAMs can be
      further divided into two groups: group I (intronless) and group II (intron
      containing). To date, tAdams have only been reported in placental mammals, and
      their evolutionary origin and relationship to sAdams remain largely unknown.
      Using phylogenetic and syntenic tools, we analyzed the Adam genes in various
      vertebrates ranging from fishes to placental mammals. Our analyses reveal
      duplication and loss of some sAdams in certain vertebrate species. In particular,
      there exists an Adam9-like gene in non-mammalian vertebrates but not mammals. We
      also identified putative group I and group II tAdams in all amniote species that
      have been examined. These tAdam homologues are more closely related to Adams 9
      and 9-like than to other sAdams. In all amniote species examined, group II tAdams
      lie in close vicinity to Adam9 and hence likely arose from tandem duplication,
      whereas group I tAdams likely originated through retroposition because of their
      lack of introns. Clusters of multiple group I tAdams are also common, suggesting
      tandem duplication after retroposition. Therefore, Adam9/9-like and some of the
      derived tAdam loci are likely preferred targets for tandem duplication and/or
      retroposition. Consistent with this hypothesis, we identified a young retroposed
      gene that duplicated recently from Adam9 in the opossum. As a result of gene
      duplication, some tAdams were pseudogenized in certain species, whereas others
      acquired new expression patterns and functions. The rapid duplication of Adam
      genes has a major contribution to the diversity of ADAMs in various vertebrate
      species. 

PMID- 26308363
TI  - New Therapies, Evidence, and Guidance in Hepatitis C Management: Expert Practices
      and Insights from an Educational Symposium at the AMCP 27th Annual Meeting Expo.
AB  - BACKGROUND: The 2013-2014 approvals of new direct-acting antiviral (DAA)
      therapies for hepatitis C virus (HCV) infection have engendered a paradigm shift
      in HCV treatment and management, offering the potential for a cure at a
      population level. The availability of the highly effective and relatively safe
      DAAs prompted revisions to guidance recommendations based on new clinical trial
      evidence. In the context of this paradigm shift and considerations of the costs
      associated with the new DAAs, managed care professionals face new questions and
      challenges regarding HCV treatment and management approaches. To address the
      continuing education needs of this group, PRIME Education, Inc. (PRIME) conducted
      a symposium on HCV at the 27th Annual Meeting Expo of the Academy of Managed Care
      Pharmacy. Moderated by Michael R. Stinchon, Jr., RPh, the program panel featured
      2 internationally recognized leaders in hepatitis C treatment and research: Norah
      Terrault, MD, MPH, and Alex Monto, MD.  OBJECTIVE: To summarize the educational
      symposium presentations and discussions. METHODS: This article is organized by
      key questions that the panelists and attendees raised for discussion during the 2
      hour symposium. The questions addressed methods for assessing liver fibrosis;
      comprehensive patient assessment to inform treatment decisions; the influence of
      viral load on decisions about treatment duration; the role of ribavirin in
      optimizing treatment efficacy; unmet treatment needs for patients with HCV
      genotype 3 or advanced liver disease; and managed care strategies for patient
      education, adherence promotion, and care coordination. In answering attendee
      questions on these issues, the expert panelists presented established evidence,
      and recognizing limitations to current evidence and guidance recommendations,
      they discussed applications of clinical judgment and offered their views and
      practices regarding individualized care for patients with HCV.  SUMMARY: In
      response to questions about the utility of noninvasive methods for assessing
      liver fibrosis, the expert panel presented a comparative overview of the
      methodology, accuracy, risks, limitations, and costs of noninvasive tests and
      liver biopsy. Discussion highlighted the strengths of noninvasive methods for
      diagnosing advanced disease and cirrhosis and the methods' limitations that pose
      barriers to ensuring that patients receive necessary antiviral therapy. Based on
      guidance recommendations, treatment should be prioritized in patients with
      advanced fibrosis or cirrhosis (Metavir score F3 to F4). While acknowledging the
      importance of this recommendation, the symposium panelists also argued that
      making effective decisions about whom, and when, to treat requires a more
      comprehensive clinical approach to patient assessment and adjusting recommended
      priorities according to individual patient considerations. This approach involves
      evaluating outcomes such as extrahepatic complications, including those affecting
      quality of life, functional status, and work productivity. In response to
      questions regarding decisions about DAA therapy duration based on viral load, the
      panel engaged the audience in thinking critically about evidence-based cutoff
      values and natural fluctuations of HCV RNA concentrations. Discussions centered
      on the importance of clinical judgment to ensure that the treatment duration
      promotes the highest efficacy and avoids risks of relapse. The panel responded to
      several audience questions about the role of ribavirin in new DAA regimens.
      Evidence-based presentations and discussions focused on patient-specific factors
      that must be considered to inform effective decisions about adding ribavirin. The
      panel took a similar approach to answering questions about emerging challenges
      and the difficult-to-treat populations of patients with HCV genotype 3 or
      advanced liver disease. The symposium concluded with presentation of, and
      discussion on, managed care strategies for educating patients about appropriate
      HCV medication use, improving adherence, and coordinating care provided by the
      interprofessional team.  CONCLUSIONS: The availability of new DAAs for HCV raises
      new questions and challenges for managed care professionals, especially regarding
      prioritizing patients for immediate therapy as well as treatment and management
      approaches that account for the needs of individual patients and subpopulations.
      The educational symposium summarized in this article directly addressed key
      questions and challenges through presentations of evidence, guidance
      recommendations, and interactive discussions on the views and practices of
      international leaders in HCV treatment and research.

PMID- 26308362
TI  - Using DNA Metabarcoding to Identify the Floral Composition of Honey: A New Tool
      for Investigating Honey Bee Foraging Preferences.
AB  - Identifying the floral composition of honey provides a method for investigating
      the plants that honey bees visit. We compared melissopalynology, where pollen
      grains retrieved from honey are identified morphologically, with a DNA
      metabarcoding approach using the rbcL DNA barcode marker and 454-pyrosequencing.
      We compared nine honeys supplied by beekeepers in the UK. DNA metabarcoding and
      melissopalynology were able to detect the most abundant floral components of
      honey. There was 92% correspondence for the plant taxa that had an abundance of
      over 20%. However, the level of similarity when all taxa were compared was lower,
      ranging from 22-45%, and there was little correspondence between the relative
      abundance of taxa found using the two techniques. DNA metabarcoding provided much
      greater repeatability, with a 64% taxa match compared to 28% with
      melissopalynology. DNA metabarcoding has the advantage over melissopalynology in
      that it does not require a high level of taxonomic expertise, a greater sample
      size can be screened and it provides greater resolution for some plant families.
      However, it does not provide a quantitative approach and pollen present in low
      levels are less likely to be detected. We investigated the plants that were
      frequently used by honey bees by examining the results obtained from both
      techniques. Plants with a broad taxonomic range were detected, covering 46
      families and 25 orders, but a relatively small number of plants were consistently
      seen across multiple honey samples. Frequently found herbaceous species were
      Rubus fruticosus, Filipendula ulmaria, Taraxacum officinale, Trifolium spp.,
      Brassica spp. and the non-native, invasive, Impatiens glandulifera. Tree pollen
      was frequently seen belonging to Castanea sativa, Crataegus monogyna and species
      of Malus, Salix and Quercus. We conclude that although honey bees are considered
      to be supergeneralists in their foraging choices, there are certain key species
      or plant groups that are particularly important in the honey bees environment.
      The reasons for this require further investigation in order to better understand
      honey bee nutritional requirements. DNA metabarcoding can be easily and widely
      used to investigate floral visitation in honey bees and can be adapted for use
      with other insects. It provides a starting point for investigating how we can
      better provide for the insects that we rely upon for pollination. 

PMID- 26308364
TI  - Palladium-catalyzed highly regioselective 6-exo-dig cyclization and alkenylation
      of ortho-ethynylanilides: the synthesis of polyene-substituted
      benzo[d][1,3]oxazines.
AB  - A Pd-catalyzed highly regioselective 6-exo-dig cyclization/alkenylation reaction
      of ortho-ethynylanilides has been developed. This tandem cross-coupling protocol
      represents a simple, efficient, step- and atom-economic approach for the
      construction of scarcely known polyene-substituted benzo[d][1,3]oxazines in
      moderate to excellent yields with a broad substrate scope. 

PMID- 26308365
TI  - Ultraporous nanofeatured PCL-PEO microfibrous scaffolds enhance cell
      infiltration, colonization and myofibroblastic differentiation.
AB  - In the field of tissue engineering, integration of micro-porosity, nano
      topogaphical features and weattability into one three-dimensional (3D) scaffold
      remains a challenge. The extracellular matrix (ECM) mimicking feature of
      electrospun fibers endows them wide applications in tissue engineering. However,
      the tight-packing of electrospun submicron fibers hinder cell infiltration and
      further colonization. In this study, we fabricated hydrophilic, micro-porous
      scaffolds with nano-topographical cues by one-step electrospinning, and
      investigated NIH3T3 fibroblasts cell infiltration, colonization and
      myofibroblastic differentiation. The hierarchical porosity enhanced cell
      infiltration and proliferation significantly. Besides, the nano-topography
      influenced the cell actin distribution and cell morphology that stimulated
      myofibroblastic differentiation in a drastically different manner from that of
      traditional solid, smooth electrospun fibers, which may hold great potential in
      reconstructing tissues that require strong contractile forces. 

PMID- 26308367
TI  - alpha-Diimine nickel complexes of ethylene and related alkenes.
AB  - A series of nickel mono(alkene) complexes, [LNi(alkene)], which consist of
      nickel(0) and neutral alpha-diimine ligand L (L = [(2,6-iPr2C6H3)NC(Me)]2), have
      been synthesized. The bonding and structures of the complexes were studied by X
      ray diffraction, spectroscopic methods, and DFT computations. 

PMID- 26308368
TI  - Fermentation of Allium chinense Bulbs With Lactobacillus plantarum ZDY 2013 Shows
      Enhanced Biofunctionalities, and Nutritional and Chemical Properties.
AB  - In this study, fermentation of Allium chinense bulbs was carried out with
      Lactobacillus plantarum ZDY 2013. A decrease in pH from 6.8 to 3.5 and a stable
      lactic acid bacteria population were observed during 7-d fermentation. The total
      phenolic content increased by 2.7-fold in the aqueous and ethanol extracts of A.
      chinense bulbs after fermentation. Antioxidant capacity including 2,2-diphenyl-1
      picrylhydrazyl radical-scavenging effect and reducing power of both extracts was
      significantly (P < 0.05) improved after fermentation. Antagonistic test against 6
      pathogens showed that fermentation significantly (P < 0.05) enhanced the
      antimicrobial activity in both extracts of fermented bulbs, especially in the
      ethanol extracts of fermented bulbs against L. monocytogenes. Analysis of the
      free amino acid (FAA) profile by ion-exchange chromatography revealed that
      fermentation significantly (P < 0.05) increased total FAA content. In addition,
      among 27 kinds of volatile components analyzed by headspace-solid phase
      microextraction-gas chromatography-tandem mass spectrometry, sulfur-containing
      compounds accounted for 65.23%, but decreased to 43.65% after fermentation. Our
      results suggested that fermentation of A. chinense bulbs with L. plantarum could
      improve their biofunctionalities, and nutritional and chemical properties.

PMID- 26308369
TI  - Optimal model-based design of the twin-column CaptureSMB process improves
      capacity utilization and productivity in protein A affinity capture.
AB  - Multi-column chromatographic processes have recently been developed for protein A
      affinity chromatography to efficiently capture monoclonal antibodies from cell
      culture supernatant. In this work, the novel twin-column CaptureSMB process was
      compared to a batch capture process with dual loading flow rate to identify
      performance gains. As a case study, the isolation of a monoclonal antibody with
      the Amsphere JWT-203 protein A resin was investigated. Using model based
      optimization, both processes were optimized and compared over a wide range of
      operating conditions. A trade-off between productivity and capacity utilization
      was found, and the resulting pareto-curves showed that CaptureSMB dominates
      batch, except at very low productivity values. With a feed titer of 1.2 mg mL(-1)
      , CaptureSMB could reach a productivity of up to 19.5 mg mL(-1) h(-1)
      experimentally, while maintaining relatively high capacity utilization of 63.8%.
      On the other hand, at maximum capacity utilization of 95.5%, a productivity of
      10.2 mg mL(-1) h(-1) could be reached. This corresponds to a performance
      improvement with respect batch operation of about 25% in capacity utilization and
      40% in productivity, for given yield and purity. CaptureSMB therefore offers a
      greatly increased performance over batch capture. 

PMID- 26308370
TI  - A newborn with three cochlear turns: Case report and literature review.
AB  - Objectives/Hypothesis: The human cochlea is most commonly considered to have two
      and a half turns. Although the causes of cochlear hypoplasia are well described,
      cochlear hyperplasia is a rarer entity that is poorly understood. We describe
      rare anatomic cochlear malformations identified in a 4-month-old male originally
      referred for evaluation after a failed newborn hearing screening. The full
      diagnostic evaluation, imaging findings, treatment, and follow-up are described
      in detail. Cochleae with three turns are an uncommon malformation that is not
      included in current classifications schemes and may represent a distinct type of
      anomaly not caused by developmental arrest.

PMID- 26308371
TI  - Aligned Growth of Hexagonal Boron Nitride Monolayer on Germanium.
AB  - A hexagonal boron nitride monolayer with aligned orientations is grown on
      reusable semiconducting germanium. The number of primary orientations of the h-BN
      domains depends on the symmetry of the underlying crystal face, and Ge (110)
      gives rise to only two opposite orientations. The structures and electrical
      properties of grain boundaries between h-BN domains with opposite orientations
      are also systematically analyzed. 

PMID- 26308372
TI  - A global proteomic study identifies distinct pathological features of IgG4
      related and primary sclerosing cholangitis.
AB  - AIMS: This combined proteomic and histopathological study was aimed to compare
      tissue characteristics of immunoglobulin (Ig)G4-related sclerosing cholangitis
      (ISC) and primary sclerosing cholangitis (PSC) in a global, non-biased manner.
      METHODS AND RESULTS: Tissue proteomes and phosphorylomes of frozen large bile
      duct samples were analysed by a conventional liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) protocol and additional phosphopeptide enrichment
      methods. The proteomic examination identified 23 373 peptides and 4870 proteins,
      including 4801 phosphopeptides and 1121 phosphoproteins. The expression profiles
      of phosphopeptides discriminated ISC from PSC more clearly than those of non
      phosphopeptides. In the pathway analysis, ISC was found to have 11 more activated
      signal cascades, including three immunological pathways, all B cell- or
      immunoglobulin-related. On immunostaining, two immunological markers (FYN-binding
      protein and allograft inflammatory factor-1) up-regulated in ISC were expressed
      mainly in M2 macrophages, consistent with increased phagocytotic activity induced
      by the immunoglobulin (Ig)G-Fcgamma receptor interaction. In contrast, PSC had
      two more activated signal pathways related to extracellular matrix (ECM)
      remodelling. Filamin-A involved in ECM remodelling was expressed aberrantly in
      injured bile ducts and associated cholangiocarcinomas in PSC, suggesting its
      possible roles in periductal fibrosis and carcinogenesis in PSC. CONCLUSIONS:
      This study suggested crucial roles of B cells and macrophages in ISC, and more
      dynamic ECM remodelling in PSC.

PMID- 26308373
TI  - Androgen receptor binding to an androgen-responsive element in the promoter of
      the Srsf4 gene inhibits its expression in mouse Sertoli cells.
AB  - The serine/arginine-rich splicing actor 4 (SRSF4) is essential for pre-mRNA
      splicing and can influence alternative-splice-site choice. Little is known about
      the specific function of this gene in the reproductive system, although a recent
      study identified a SRSF4 polymorphism significantly associated with a decreased
      risk of non-obstructive azoospermia in Chinese men. We previously found that the
      expression of Srsf4 was up-regulated in the testes of Sertoli-cell-selective
      androgen receptor knockout (S-Ar(-/y)) mice compared to wild-type mice using
      digital gene expression analysis. In this study, we confirmed and extended the
      selective gene expression data: SRSF4 was mainly located in the nucleus of
      Sertoli cells, and Srsf4 expression in the Sertoli-cell-derived cell line TM4 is
      down-regulation by testosterone. Moreover, androgen receptor directly binds the
      androgen-responsive element of the Srsf4 promoter. Taken together, these results
      demonstrate that Srsf4 is a direct downstream target of the androgen receptor in
      mouse Sertoli cells.

PMID- 26308374
TI  - Dye monolayers used as the hole transporting medium in dye-sensitized solar
      cells.
AB  - Dye-sensitized TiO2 can be used as the active layer of solar-cell devices without
      an additional hole-transporting material. In this architecture, holes are
      transported through the dye monolayer. 

PMID- 26308375
TI  - Large dynamic range relative B1+ mapping.
AB  - PURPOSE: Parallel transmission (PTx) requires knowledge of the B1+ produced by
      each element. However, B1+ mapping can be challenging when transmit fields
      exhibit large dynamic range. This study presents a method to produce high quality
      relative B1+ maps when this is the case. THEORY AND METHODS: The proposed
      technique involves the acquisition of spoiled gradient echo (SPGR) images at
      multiple radiofrequency drive levels for each transmitter. The images are
      combined using knowledge of the SPGR signal equation using maximum likelihood
      estimation, yielding an image for each channel whose signal is proportional to
      the B1+ field strength. Relative B1+ maps are then obtained by taking image
      ratios. The method was tested using numerical simulations, phantom imaging, and
      through in vivo experiments. RESULTS: The numerical simulations demonstrated that
      the proposed method can reconstruct relative transmit sensitivities over a wide
      range of B1+ amplitudes and at several SNR levels. The method was validated at 3
      Tesla (T) by comparing it with an alternative B1+ mapping method, and
      demonstrated in vivo at 7T. CONCLUSION: Relative B1+ mapping in the presence of
      large dynamic range has been demonstrated through numerical simulations, phantom
      imaging at 3T and experimentally at 7T. The method will enable PTx to be applied
      in challenging imaging scenarios at ultrahigh field. Magn Reson Med 76:490-499,
      2016. (c) 2015 The Authors. Magnetic Resonance in Medicine published by Wiley
      Periodicals, Inc. on behalf of International Society for Magnetic Resonance in
      Medicine. This is an open access article under the terms of the Creative Commons
      Attribution License, which permits use, distribution and reproduction in any
      medium, provided the original work is properly cited.

PMID- 26308376
TI  - Preferences of advanced cancer patients for communication on anticancer treatment
      cessation and the transition to palliative care.
AB  - BACKGROUND: The objective of this study was to clarify the communication
      preferences of patients with advanced cancer regarding discussions about ending
      anticancer treatment and transitioning to palliative care and to explore the
      variables associated with those preferences. METHODS: Participants were 106
      Japanese patients with cancer who had been informed at least 1 week earlier about
      the cessation of their anticancer treatment. They completed a survey measuring
      their preferences for communication about ending anticancer treatment and
      transitioning to palliative care as well as their demographic characteristics.
      Medical records were also examined to investigate medical characteristics.
      RESULTS: Results of the descriptive analysis indicated that patients strongly
      preferred their physicians to listen to their distress and concerns (96%), to
      assure them that their painful symptoms would be controlled (97.1%), and to
      explain the status of their illness and the physical symptoms that would likely
      occur in the future (95.1%). Multiple regression analyses identified the factors
      associated with these preferences: telling patients to prepare mentally and
      informing them of their expected life expectancy were associated with cancer
      site; sustaining hope was associated with cancer site and children; and empathic
      paternalism was associated with duration since cancer diagnosis. CONCLUSIONS: The
      majority of patients preferred their physicians to be realistic about their
      likely future and wanted to be reassured that their painful symptoms would be
      controlled. For patients with cancer at certain sites, those with children, and
      those more recently diagnosed, physicians should communicate carefully and
      actively by providing information on life expectancy and mental preparation,
      sustaining hope, and behaving with empathic paternalism.

PMID- 26308377
TI  - Revealing the role of Pb(2+) in the stability of organic-inorganic hybrid
      perovskite CH3NH3Pb1-xCdxI3: an experimental and theoretical study.
AB  - This paper presents the synthesis of organic-inorganic hybrid perovskite
      CH3NH3Pb1-xCdxI3. The effect of incorporating Cd(2+) or Pb(2+) on the stability
      of the perovskite structure was analysed from a theoretical and experimental
      viewpoint. The XRD results showed that the tetragonal perovskite structure was
      formed for x values of up to 0.5, which seems to indicate that the presence of a
      considerable amount of Pb(2+) is necessary to stabilise the structure. In turn,
      UV-Vis spectroscopy showed how the presence of Cd(2+) led to a reduction in the
      optical band gap of the perovskite structure of up to 9% for CH3NH3Pb0.5Cd0.5I3
      with regard to the MAPbI3 structure. Moreover, periodic-DFT calculations were
      performed to understand the effect of the increased concentration of Cd on the
      structural and electronic properties of MAPbI3 perovskites. The analysis of both
      the ELF and the non-covalent interaction (NCI) index show the important role
      played by the Pb(2+) ions in stabilizing this kind of hybrid perovskite
      structures. Finally, the DOS analysis confirmed the experimental results obtained
      using UV-Vis spectroscopy. The theoretical band gap values decreased as the
      concentration of Cd increased. 

PMID- 26308378
TI  - ATAD2 overexpression links to enrichment of B-MYB-translational signatures and
      development of aggressive endometrial carcinoma.
AB  - We have explored the potential for clinical implementation of ATAD2 as a
      biomarker for aggressive endometrial cancer by investigating to what extent
      immunohistochemical (IHC) staining for ATAD2 is feasible, reflects clinical
      phenotype and molecular subgroups of endometrial carcinomas. Increased expression
      of the ATAD2 gene has been implicated in cancer development and progression in a
      number of tissues, but few studies have investigated ATAD2 expression using IHC.
      Here we show that high ATAD2 protein expression is significantly associated with
      established clinical-pathological variables for aggressive endometrial cancer,
      also in the subset of estrogen receptor alpha (ERalpha) positive tumors. Protein
      and mRNA expression of ATAD2 were highly correlated (P < 0.001), suggesting that
      IHC staining may represent a more clinically applicable measure of ATAD2 level in
      routinely collected formalin fixed paraffin embedded specimens. Gene expression
      alterations in samples with high ATAD2 expression revealed upregulation of
      several cancer-related genes (B-MYB, CDCs, E2Fs) and gene sets that previously
      have been linked to aggressive disease and potential for new targeting therapies.
      Our results support that IHC staining for ATAD2 may be a clinically applicable
      biomarker reflecting clinical phenotype and targetable alterations in endometrial
      carcinomas to be further explored in controlled clinical trials. 

PMID- 26308379
TI  - Generation of multiple reporter ions from a single isobaric reagent increases
      multiplexing capacity for quantitative proteomics.
AB  - Isobaric labeling strategies for mass spectrometry-based proteomics enable
      multiplexed simultaneous quantification of samples and therefore substantially
      increase the sample throughput in proteomics. However, despite these benefits,
      current limits to multiplexing capacity are prohibitive for large sample sizes
      and impose limitations on experimental design. Here, we introduce a novel
      mechanism for increasing the multiplexing density of isobaric reagents. We
      present Combinatorial Isobaric Mass Tags (CMTs), an isobaric labeling
      architecture with the unique ability to generate multiple series of reporter ions
      simultaneously. We demonstrate that utilization of multiple reporter ion series
      improves multiplexing capacity of CMT with respect to a commercially available
      isobaric labeling reagent with preserved quantitative accuracy and depth of
      coverage in complex mixtures. We provide a blueprint for the realization of 16
      plex reagents with 1 Da spacing between reporter ions and up to 28-plex at 6 mDa
      spacing using only 5 heavy isotopes per reagent. We anticipate that this
      improvement in multiplexing capacity will further advance the application of
      quantitative proteomics, particularly in high-throughput screening assays. 

PMID- 26308380
TI  - Damage Control as a Strategy to Manage Postreperfusion Hemodynamic Instability
      and Coagulopathy in Liver Transplant.
AB  - IMPORTANCE: Damage control (DC) with intra-abdominal packing and delayed
      reconstruction is an accepted strategy in trauma and acute care surgery but has
      not been evaluated in liver transplant. OBJECTIVE: To evaluate the incidence,
      effect on survival, and predictors of the need for DC using intra-abdominal
      packing and delayed biliary reconstruction in patients with coagulopathy or
      hemodynamic instability after liver allograft reperfusion. DESIGN, SETTING, AND
      PARTICIPANTS: We performed a retrospective analysis of adults undergoing liver
      transplant at a large transplant center from February 1, 2002, through July 31,
      2012. MAIN OUTCOMES AND MEASURES: Predictors of DC, effects on graft, and patient
      survival. RESULTS: Of 1813 patients, 150 (8.3%) underwent DC during liver
      transplant, with 84 (56.0%) requiring a single additional operation for biliary
      reconstruction and abdominal closure and 57 (38.0%) requiring multiple additional
      operations. Compared with recipients without DC, patients requiring DC had
      greater Model for End-stage Liver Disease scores (33 vs 27; P < .001); more
      frequent pretransplant hospitalization (72.0% vs 47.9%; P < .001), intubation
      (33.3% vs 19.9%; P < .001), vasopressors (23.2% vs 10.9%; P < .001), renal
      replacement therapy (49.6% vs 30.3%; P < .001), and prior major abdominal
      operations (48.3% vs 21.9%; P < .001), including prior liver transplant (29.3% vs
      8.9%; P < .001); greater operative transfusion requirements (37 vs 13 units of
      packed red blood cells; P < .001); worse intraoperative base deficit (10.3 vs
      8.4; P = .03); more frequent postreperfusion syndrome (56.2% vs 27.3%; P < .001);
      and longer cold (430 vs 404 minutes; P = .04) and warm (46 vs 41 minutes; P <
      .001) ischemia times. Patients who underwent DC followed by a single additional
      operation for biliary reconstruction and abdominal closure had similar 1-, 3-,
      and 5-year graft survival (71%, 62%, and 62% vs 81%, 71%, and 67%; P = .26) and
      patient survival (72%, 64%, and 64% vs 84%, 75%, and 70%; P = .15) compared with
      recipients not requiring DC. Multivariate predictors of DC included prior liver
      transplant or major abdominal operation, longer pretransplant recipient and donor
      length of stay, greater Model for End-stage Liver Disease score, and longer warm
      and cold ischemia times (C statistic, 0.75). CONCLUSIONS AND RELEVANCE: To our
      knowledge, this study represents the first large report of DC as a viable
      strategy for liver transplant recipients with coagulopathy or hemodynamic
      instability after allograft reperfusion. In DC recipients not requiring
      additional operations, outcomes are excellent and comparable to 1-stage liver
      transplant.

PMID- 26308381
TI  - What's more general than a whole population?
AB  - Statistical inference is commonly said to be inapplicable to complete population
      studies, such as censuses, due to the absence of sampling variability.
      Nevertheless, in recent years, studies of whole populations, e.g., all cases of a
      certain cancer in a given country, have become more common, and often report p
      values and confidence intervals regardless of such concerns. With reference to
      the social science literature, the current paper explores the circumstances under
      which statistical inference can be meaningful for such studies. It concludes that
      its use implicitly requires a target population which is wider than the whole
      population studied - for example future cases, or a supranational geographic
      region - and that the validity of such statistical analysis depends on the
      generalizability of the whole to the target population. 

PMID- 26308382
TI  - Breaking the Myth That Relay Swimming Is Faster Than Individual Swimming.
AB  - PURPOSE: To investigate if swimming performance is better in a relay race than in
      the corresponding individual race. METHODS: The authors analyzed 166 elite male
      swimmers from 15 nations in the same competition (downloaded from
      www.swimrankings.net). Of 778 observed races, 144 were Olympic Games performances
      (2000, 2004, 2012), with the remaining 634 performed in national or international
      competitions. The races were 100-m (n = 436) and 200-m (n = 342) freestyle
      events. Relay performance times for the 2nd-4th swimmers were adjusted (+ 0.73 s)
      to allow for the "flying start." RESULTS: Without any adjustment, mean individual
      relay performances were significantly faster for the first 50 m and overall time
      in the 100-m events. Furthermore, the first 100 m of the 200-m relay was
      significantly faster (P > .001). During relays, swimmers competing in 1st
      position did not show any difference compared with their corresponding individual
      performance (P > .16). However, swimmers competing in 2nd-4th relay-team
      positions demonstrated significantly faster times in the 100-m (P < .001) and
      first half of the 200-m relays than in their individual events (P < .001, ES:
      0.28-1.77). However, when finishing times for 2nd-4th relay team positions were
      adjusted for the flying start no differences were detected between relay and
      individual race performance for any event or split time (P > .17). CONCLUSION:
      Highly trained swimmers do not swim (or turn) faster in relay events than in
      their individual races. Relay exchange times account for the difference observed
      in individual vs relay performance.

PMID- 26308383
TI  - Chemically Modulated Band Gap in Bilayer Graphene Memory Transistors with High
      On/Off Ratio.
AB  - We report a chemically conjugated bilayer graphene field effect transistor
      demonstrating a high on/off ratio without significant degradation of the on
      current and mobility. This was realized by introducing environmentally stable
      benzyl viologen as an electron-donating group and atmospheric dopants as an
      electron-withdrawing group, which were used as dopants for the bottom and top of
      the bilayer graphene, respectively. A high mobility of ~3100 cm(2) V(-1) s(-1)
      with a high on/off ratio of 76.1 was obtained at room temperature without
      significant degradation of the on-current. This is attributed to low charge
      scattering due to physisorbed dopants without provoking sp(3) structural
      disorders. By utilizing our band-gap-opened bilayer graphene, excellent
      nonvolatile memory switching behavior was demonstrated with a clear program/erase
      state by applying pulse gate bias. The initial program/erase current ratio of
      ~34.5 was still retained at higher than 10 even after 10(4) s. 

PMID- 26308384
TI  - A Methodology for Integrated, Multiregional Life Cycle Assessment Scenarios under
      Large-Scale Technological Change.
AB  - Climate change mitigation demands large-scale technological change on a global
      level and, if successfully implemented, will significantly affect how products
      and services are produced and consumed. In order to anticipate the life cycle
      environmental impacts of products under climate mitigation scenarios, we present
      the modeling framework of an integrated hybrid life cycle assessment model
      covering nine world regions. Life cycle assessment databases and multiregional
      input-output tables are adapted using forecasted changes in technology and
      resources up to 2050 under a 2  degrees C scenario. We call the result of this
      modeling "technology hybridized environmental-economic model with integrated
      scenarios" (THEMIS). As a case study, we apply THEMIS in an integrated
      environmental assessment of concentrating solar power. Life-cycle greenhouse gas
      emissions for this plant range from 33 to 95 g CO2 eq./kWh across different world
      regions in 2010, falling to 30-87 g CO2 eq./kWh in 2050. Using regional life
      cycle data yields insightful results. More generally, these results also
      highlight the need for systematic life cycle frameworks that capture the actual
      consequences and feedback effects of large-scale policies in the long term. 

PMID- 26308385
TI  - Polycythemia following allogeneic hematopoietic progenitor cell transplantation
      occurring during iron chelation therapy.

PMID- 26308387
TI  - Single-Digit Pathogen and Attomolar Detection with the Naked Eye Using Liposome
      Amplified Plasmonic Immunoassay.
AB  - We introduce an enzyme-free plasmonic immunoassay with a binary (all-or-none)
      response. The presence of a single pathogen in the sample results in a chemical
      cascade reaction leading to a large red to dark-blue colorimetric shift visible
      to the naked eye. The immediate and amplified response is initiated by a
      triggered breakdown of cysteine-loaded nanoliposomes and subsequent aggregation
      of plasmonic gold nanoparticles. Our approach enabled visual detection of a
      single-digit live pathogen of Salmonella, Listeria, and E. coli O157 in water and
      food samples. Furthermore, the assay allowed a naked-eye detection of target
      antibody concentrations as low as 6.7 attomolar (600 molecules in 150 MUL); six
      orders of magnitude lower than conventional enzyme-linked immunosorbent assay
      (ELISA). 

PMID- 26308388
TI  - Composite Transparent Electrode of Graphene Nanowalls and Silver Nanowires on
      Micropyramidal Si for High-Efficiency Schottky Junction Solar Cells.
AB  - The conventional graphene-silicon Schottky junction solar cell inevitably
      involves the graphene growth and transfer process, which results in complicated
      technology, loss of quality of the graphene, extra cost, and environmental
      unfriendliness. Moreover, the conventional transfer method is not well suited to
      conformationally coat graphene on a three-dimensional (3D) silicon surface. Thus,
      worse interfacial conditions are inevitable. In this work, we directly grow
      graphene nanowalls (GNWs) onto the micropyramidal silicon (MP) by the plasma
      enhanced chemical vapor deposition method. By controlling growth time, the cell
      exhibits optimal pristine photovoltaic performance of 3.8%. Furthermore, we
      improve the conductivity of the GNW electrode by introducing the silver nanowire
      (AgNW) network, which could achieve lower sheet resistance. An efficiency of 6.6%
      has been obtained for the AgNWs-GNWs-MP solar cell without any chemical doping.
      Meanwhile, the cell exhibits excellent stability exposed to air. Our studies show
      a promising way to develop simple-technology, low-cost, high-efficiency, and
      stable Schottky junction solar cells. 

PMID- 26308389
TI  - The Validity of YouTube Videos on Pediatric BLS and CPR.
AB  - BACKGROUND: There are few data regarding the validity of cardiopulmonary
      resuscitation (CPR) and basic life support (BLS) videos on YouTube in the medical
      literature, and those that do are only analyzing adult CPR videos. The present
      study aimed to determine the reliability and accuracy of pediatric CPR and BLS
      videos as to whether they are consistent with the 2010 CPR guidelines. MATERIALS
      AND METHODS: YouTube was scanned in January 2015 using the key words "Pediatric
      CPR Pediatric BLS" without any filters. The raw data collected in the study
      included sources that uploaded the videos, the record time, the number of viewers
      in the study period, and inclusion of human or mannequins. Furthermore, the
      contents of the videos were evaluated as to whether they are consistent with the
      2010 resuscitation guidelines. All videos were seen by two independent
      researchers (emergency physicians) and scored between 0 and 8. RESULTS: In total,
      1,200 videos were evaluated regarding the exclusion criteria, which yielded 232
      eligible ones. Most of the videos were found to be uploaded by individuals with
      unspecified credentials (34.1%). Of the videos, 15.5% have content inconsistent
      with the 2010 guidelines. The median score of all the videos are not high enough
      (5 [interquartile range (IQR), 4-7]), and only one-third of the videos have
      optimal quality with scores of 7 or 8. The downloaded number of videos compatible
      with guidelines was significantly higher relative to the videos not compatible
      with the guidelines (15,389 [IQR, 881-31515] versus 477 [IQR, 108-3,797); p =
      0.0001). The videos downloaded more than 10,000 times had a higher score than the
      others (median scores of 7 and 5, respectively; p = 0.0001). CONCLUSIONS:
      Moderate numbers of YouTube videos purporting to be about pediatric life support
      have optimal quality, and few of them are perfect. Furthermore, YouTube videos
      uploaded by news programs with an insufficient quality have the highest download
      rates.

PMID- 26308386
TI  - Minireview: Roles of Fibroblast Growth Factors 19 and 21 in Metabolic Regulation
      and Chronic Diseases.
AB  - Fibroblast growth factor (FGF)19 and FGF21 are hormones that regulate metabolic
      processes particularly during feeding or starvation, thus ultimately influencing
      energy production. FGF19 is secreted by the intestines during feeding and
      negatively regulates bile acid synthesis and secretion, whereas FGF21 is produced
      in the liver during fasting and plays a crucial role in regulating glucose and
      lipid metabolism, as well as maintaining energy homeostasis. FGF19 and FGF21 are
      regarded as late-acting hormones because their functions are only used after
      insulin and glucagon have completed their actions. Although FGF19 and FGF21 are
      activated under different conditions, they show extensively functional overlap in
      terms of improving glucose tolerance, insulin sensitivity, weight loss, and
      lipid, and energy metabolism, particularly in pathological conditions such as
      diabetes, obesity, metabolic syndrome, and cardiovascular and renal diseases.
      Most patients with these metabolic diseases exhibit reduced serum FGF19 levels,
      which might contribute to its etiology. In addition, the simultaneous increase in
      serum FGF21 levels is likely a compensatory response to reduced FGF19 levels, and
      the 2 proteins concertedly maintain metabolic homeostasis. Here, we review the
      physiological and pharmacological cross talk between FGF19 and FGF21 in relation
      to the regulation of endocrine metabolism and various chronic diseases. 

PMID- 26308390
TI  - Factors involved in the identification of stuttering severity in a foreign
      language.
AB  - Speech-language pathologists nowadays are more and more confronted with clients
      who speak a language different from their own mother tongue. The assessment of
      persons who speak a foreign language poses particular challenges. The present
      study investigated the possible role and interplay of factors involved in the
      identification of stuttering severity in a foreign language. Nineteen speech
      language pathologists from five different countries (i.e. Iceland, Sweden,
      Norway, Finland, and Belgium) rated stuttering severity of speech samples
      featuring persons who stutter speaking Icelandic, Swedish, Norwegian, or Dutch.
      Additionally, they were asked to score how easy they found it to rate the
      samples. Accuracy of rating stuttering severity in another language appeared to
      be foremost determined by the client's stuttering severity, while experienced
      ease of rating stuttering severity was essentially related to closeness of the
      language of the clinician to that of the client and familiarity of the clinician
      with the client's language. Stuttering measurement training programmes in
      different languages are needed. 

PMID- 26308391
TI  - Ways to Avoid and Dodge Plagiarism in Scientific Writing? Personal Experience.

PMID- 26308392
TI  - Peptide Bond Formation in Water Mediated by Carbon Disulfide.
AB  - Demonstrating plausible nonenzymatic polymerization mechanisms for prebiotic
      monomers represents a fundamental goal in prebiotic chemistry. While a great deal
      is now known about the potentially prebiotic synthesis of amino acids, our
      understanding of abiogenic polymerization processes to form polypeptides is less
      well developed. Here, we show that carbon disulfide (CS2), a component of
      volcanic emission and sulfide mineral weathering, and a widely used synthetic
      reagent and solvent, promotes peptide bond formation in modest yields (up to
      ~20%) from alpha-amino acids under mild aqueous conditions. Exposure of a variety
      of alpha-amino acids to CS2 initially yields aminoacyl dithiocarbamates, which in
      turn generate reactive 2-thiono-5-oxazolidone intermediates, the thio analogues
      of N-carboxyanhydrides. Along with peptides, thiourea and thiohydantoin species
      are produced. Amino acid stereochemistry was preserved in the formation of
      peptides. Our findings reveal that CS2 could contribute to peptide bond
      formation, and possibly other condensation reactions, in abiogenic settings.

PMID- 26308393
TI  - The physiological effects of human immunoglobulin on severe bronchiolitis
      patients before and after treatment.
AB  - The goal of the present study is to explore the physiological effects of injected
      human immunoglobulin on patients with severe bronchiolitis before and after
      treatment. 86 young children with severe bronchiolitis were randomly divided into
      the observation group (43 cases) and the treatment group (43 cases). On the basis
      of conventional therapy, the children in the treatment group were given human
      immunoglobulin (400 mg/kg, 1-3 times) via intravenous injection. 60 healthy young
      children, as determined by a physical examination given at the Zhumadian Central
      Hospital, were enrolled as the control group. The T lymphocytes, cytokines, IgA,
      IgG, and IgM immunoglobulins in the peripheral blood of all 3 groups were
      measured. The clinical efficacy of the immunoglobulins to mitigate the effects of
      bronchiolitis and the amount of time for the reduction of symptoms to occur were
      observed. The serum Ca, Fe, and Zn levels of children with severe bronchiolitis
      were significantly lower than those of the healthy control group (p < 0.05). As
      such, the CD8, IgA, IgG, IgM and IFN-gamma levels were also significantly lower
      in the children with severe bronchiolitis than in the children in the healthy
      control group (p < 0.05). Furthermore, the CD4, IgE, IL-4, and IL-4/IFN-gamma
      levels and CD4/CD8 ratio were dramatically higher than in the healthy control
      group (p < 0.05). Serum levels of the aforementioned indicators either increased
      or decreased after IVIG treatment. The amount of time required for coughing,
      wheezing, and pulmonary rales to seize, and the duration of illness for the
      children with the severe bronchiolitis children was significantly shorter for
      those in the treatment group than for those in the observation group. Human
      immunoglobulin via intravenous injection showed active therapeutical effects on
      trace elements, T lymphocytes, and cytokines in patients with severe
      bronchiolitis.

PMID- 26308394
TI  - Flurbiprofen: A Nonselective Cyclooxygenase (COX) Inhibitor for Treatment of
      Noninfectious, Non-necrotizing Anterior Scleritis.
AB  - OBJECTIVE: To analyze the safety and efficacy of a nonselective cyclo-oxygenase
      (COX) inhibitor in the management of noninfectious, non-necrotizing anterior
      scleritis. METHODS: Retrospective chart review of 126 patients with non
      necrotizing anterior scleritis treated with oral flurbiprofen (Froben(r)(Abbott
      Healthcare)) with (Group B, n = 61) or without (Group A, n = 65) topical steroids
      was performed and time to remission was plotted. RESULTS: The observed incidence
      rate was 1.07 (95% CI: 0.57-1.99) per 1000 person-years with failure rate of 0.68
      (95% CI: 0.22-2.12) per 1000 person-years in Group A and 1.41 (95% CI: 0.67-2.96)
      per 1000 person-years in Group B. The failure rate was 3.97 (1.89-9.34) per 1000
      person-years with hazard ratio of 10.01 (95% CI: 2.52-39.65; p < 0.001) for
      patients with associated systemic disease. CONCLUSION: To the of our best
      knowledge, this is the first and largest case series on the safety and efficacy
      of a nonselective COX inhibitor in the management of anterior scleritis.

PMID- 26308395
TI  - Comparative Functional Analysis of 12 Mammalian IFN-lambda4 Orthologs.
AB  - IFN-lambda4 is a novel type-III interferon with strong clinical significance in
      humans. Only a subset of individuals--up to 10% of Asians, 50% of Europeans, and
      90% of Africans--carry the DeltaG allele of a genetic variant rs368234815
      TT/DeltaG and are genetically able to produce IFN-lambda4 protein. Carriers of
      the DeltaG allele have impaired ability to clear infection with hepatitis C virus
      (HCV). IFN-lambda4 is also predicted to exist and be functionally important in
      several nonhuman mammals. In this study, we present the first comparative
      analysis of 12 mammalian IFN-lambda4 orthologs in a human hepatic cell line,
      HepG2, which supports signaling of the human IFN-lambda4. We show that despite
      differences in protein sequences, functional properties of the recombinant human
      and nonhuman IFN-lambda4 proteins are comparable-they are all expressed as
      predominantly cytoplasmic proteins that are biologically active for induction of
      interferon signaling. We show that several IFN-lambda4 orthologs can be detected
      by Western blotting, flow cytometry, and confocal imaging using a monoclonal
      antibody developed for the human IFN-lambda4. Studies of IFN-lambda4 in animals
      should help improve our understanding of the biology of this novel clinically
      important interferon in normal and disease conditions.

PMID- 26308397
TI  - Identification of a new STAT3 dimerization inhibitor through a pharmacophore
      based virtual screening approach.
AB  - Signal transducer and activator of transcription 3 (STAT3) plays an essential
      role in cell growth regulation and survival. An aberrant STAT3 activation and/or
      expression is implied in various solid and blood tumors as well as in other
      pathologies like rheumatoid arthritis and pulmonary fibrosis, thus making the
      search for STAT3 inhibitors a growing field of study. With the aim of identifying
      new inhibitors of STAT3 dimerization, we screened a database including more than
      1 320 000 commercially available compounds using a receptor-based pharmacophore
      model comprising the key protein-protein interactions identified in the STAT3
      dimer and refining the search through docking and molecular dynamic simulations
      studies. STAT3 binding assays revealed a significant STAT3 inhibitory activity
      and selectivity versus Grb2 for one of the four top-scored compounds, thus
      verifying the reliability of the virtual screening workflow. Moreover, such
      compound could already be considered as a lead for the development of new and
      more potent STAT3 dimerization inhibitors. 

PMID- 26308396
TI  - Preoperative biomarkers of tumour vascularity are elevated in patients with
      glioblastoma multiforme.
AB  - We investigated the correlation between the circulating and imaging biomarkers of
      tumour vascularity, and examined whether they are prognostic of outcomes in
      patients with glioblastoma multiforme (GBM). Despite the increasing use of anti
      angiogenic agents within neuro-oncology, there are still no validated biomarkers
      to monitor for a treatment response or relapse. The pre- and postoperative
      circulating endothelial cell (CEC) and progenitor cell (CEP) levels were
      assessed. Preoperative perfusion-weighted MRI (PWI) was also performed, and the
      relative cerebral blood volume (rCBV) histogram statistics of the contrast
      enhancing tumour were analysed. A novel PWI parameter (rCBVload) was developed to
      estimate the total volume of perfused tumour vessels, and it was hypothesised
      that this parameter would correlate with CEC and CEP concentrations. In total, 24
      GBM patients were included. The mean preoperative CEC concentration was
      significantly higher in GBM patients than the controls (p=0.019), and it then
      declined significantly postoperatively (p=0.009). The preoperative CEP levels
      were significantly correlated with the median tumour rCBV (Spearman rank-order
      coefficient=0.526; p=0.039). Neither CEC nor CEP was correlated with the total
      tumour vessel volume, as measured by rCBVload. None of the biomarkers that were
      investigated showed a significant correlation with progression-free or overall
      survival. We conclude that CEC are potentially useful biomarkers to monitor GBM
      patients during treatment. We found that CEC are increased in the presence of
      GBM, and that CEP levels appear to be proportional to tumour vascularity, as
      measured on PWI. However, in this study, none of the biomarkers of GBM
      vascularity were highly prognostic of patient outcomes. 

PMID- 26308398
TI  - Laboratory errors and patient safety.
AB  - PURPOSE: Laboratory data are extensively used in medical practice; consequently,
      laboratory errors have a tremendous impact on patient safety. Therefore, programs
      designed to identify and reduce laboratory errors, as well as, setting specific
      strategies are required to minimize these errors and improve patient safety. The
      purpose of this paper is to identify part of the commonly encountered laboratory
      errors throughout our practice in laboratory work, their hazards on patient
      health care and some measures and recommendations to minimize or to eliminate
      these errors. DESIGN/METHODOLOGY/APPROACH: Recording the encountered laboratory
      errors during May 2008 and their statistical evaluation (using simple percent
      distribution) have been done in the department of laboratory of one of the
      private hospitals in Egypt. Errors have been classified according to the
      laboratory phases and according to their implication on patient health. FINDINGS:
      Data obtained out of 1,600 testing procedure revealed that the total number of
      encountered errors is 14 tests (0.87 percent of total testing procedures). Most
      of the encountered errors lay in the pre- and post-analytic phases of testing
      cycle (representing 35.7 and 50 percent, respectively, of total errors). While
      the number of test errors encountered in the analytic phase represented only 14.3
      percent of total errors. About 85.7 percent of total errors were of non
      significant implication on patients health being detected before test reports
      have been submitted to the patients. On the other hand, the number of test errors
      that have been already submitted to patients and reach the physician represented
      14.3 percent of total errors. Only 7.1 percent of the errors could have an impact
      on patient diagnosis. PRACTICAL IMPLICATIONS: The findings of this study were
      concomitant with those published from the USA and other countries. This proves
      that laboratory problems are universal and need general standardization and bench
      marking measures. ORIGINALITY/VALUE: Original being the first data published from
      Arabic countries that evaluated the encountered laboratory errors and launch the
      great need for universal standardization and bench marking measures to control
      the laboratory work.

PMID- 26308399
TI  - Facilitating a just and trusting culture.
AB  - PURPOSE: The purpose of this paper is to identify managerial and organizational
      characteristics and behaviors that facilitate the fostering of a just and
      trusting culture within the healthcare system. DESIGN/METHODOLOGY/APPROACH: Two
      studies were conducted. The initial qualitative one was used to identify themes
      based on interviews with health care workers that facilitate a just and trusting
      culture. The quantitative one used a policy-capturing design to determine which
      factors were most likely to predict outcomes of manager and organizational trust.
      FINDINGS: The factors of violation type (ability vs integrity), providing an
      explanation or not, blame vs no blame by manager, and blame vs no blame by
      organization were all significant predictors of perceptions of trust. RESEARCH
      LIMITATIONS/IMPLICATIONS: Limitations to the generalizability of findings
      included both a small and non-representative sample from one health care region.
      PRACTICAL IMPLICATIONS: The present findings can be useful in developing training
      systems for managers and organizational executive teams for managing medical
      error events in a manner that will help develop a just and trusting culture.
      SOCIAL IMPLICATIONS: A just and trusting culture should enhance the likelihood of
      reporting medical errors. Improved reporting, in turn, should enhance patient
      safety. ORIGINALITY/VALUE: This is the first field study experimentally
      manipulating aspects of organizational trust within the health care sector. The
      use of policy-capturing is a unique feature that sheds light into the decision
      making of health care workers as to the efficaciousness of particular managerial
      and organizational characteristics that impact a just and trusting culture.

PMID- 26308400
TI  - An empirical study on hospital selection in India.
AB  - PURPOSE: The purpose of this paper is to understand the different factors
      patients consider in choosing a hospital in a major city in India, prior to
      admission. DESIGN/METHODOLOGY/APPROACH: A 20-item scale to identify various
      factors a patient considers in choosing a hospital was developed. A field survey
      was conducted on patients who were discharged in the recent past from a public or
      a private hospital. The data collected were analysed using multivariate
      techniques. FINDINGS: The data analysis highlighted several factors in the
      hospital choice selection process, namely quality of treatment, referral,
      transport convenience, cost, and safety and services. RESEARCH
      LIMITATIONS/IMPLICATIONS: This research study was carried out in one of the four
      major metropolitan cities of India. Nonetheless, the study provides valuable
      insights into the hospital selection process in a developing country like India.
      PRACTICAL IMPLICATIONS: Hospital managers, in general, can use the study findings
      to improve the operating performance of their hospitals so that they are able to
      attract more patients in the future. Additionally, the information can be useful
      to the marketing managers for developing appropriate marketing strategies for
      their hospitals. ORIGINALITY/VALUE: Majority of the empirical research on
      hospital choice process has been conducted in Europe and North America. Limited
      knowledge exists on the same in a developing nation like India. This research
      illustrates a comprehensive study to address that concern.

PMID- 26308401
TI  - Food production and service in UK hospitals.
AB  - PURPOSE: The purpose of this paper is to apply value stream mapping holistically
      to hospital food production/service systems focused on high-quality food.
      DESIGN/METHODOLOGY/APPROACH: Multiple embedded case study of three (two private
      sector and one public-sector) hospitals in the UK. FINDINGS: The results
      indicated various issues affecting hospital food production including: the menu
      and nutritional considerations; food procurement; food production; foodservice;
      patient perceptions/expectations. RESEARCH LIMITATIONS/IMPLICATIONS: Value stream
      mapping is a new approach for food production systems in UK hospitals whether
      private or public hospitals. PRACTICAL IMPLICATIONS: The paper identifies
      opportunities for enhancing hospital food production systems. ORIGINALITY/VALUE:
      The paper provides a theoretical basis for process enhancement of hospital food
      production and the provision of high-quality hospital food.

PMID- 26308402
TI  - Managerial process improvement: a lean approach to eliminating medication
      delivery.
AB  - PURPOSE: Statistical evidence shows that medication errors are a major cause of
      injuries that concerns all health care oganizations. Despite all the efforts to
      improve the quality of care, the lack of understanding and inability of
      management to design a robust system that will strategically target those factors
      is a major cause of distress. The paper aims to discuss these issues.
      DESIGN/METHODOLOGY/APPROACH: Achieving optimum organizational performance
      requires two key variables; work process factors and human performance factors.
      The approach is that healthcare administrators must take in account both
      variables in designing a strategy to reduce medication errors. However,
      strategies that will combat such phenomena require that managers and
      administrators understand the key factors that are causing medication delivery
      errors. FINDINGS: The authors recommend that healthcare organizations implement
      the Toyota Production System (TPS) combined with human performance improvement
      (HPI) methodologies to eliminate medication delivery errors in hospitals.
      ORIGINALITY/VALUE: Despite all the efforts to improve the quality of care, there
      continues to be a lack of understanding and the ability of management to design a
      robust system that will strategically target those factors associated with
      medication errors. This paper proposes a solution to an ambiguous workflow
      process using the TPS combined with the HPI system.

PMID- 26308403
TI  - Workshops as a useful tool to better understand care professionals' views of a
      lean change program.
AB  - PURPOSE: For change programs to succeed, it is vital to have a detailed
      understanding of employees' views regarding the program, especially when the
      proposed changes are potentially contested. Gaining insight into employee
      perceptions helps managers to decide how to proceed. The authors conducted two
      workshops in a radiotherapy institute to assess the benefits and drawbacks, as
      well as their underlying causes, of a proposed Lean change program. Managers'
      views on the workshops' usefulness were charted. The paper aims to discuss these
      issues. DESIGN/METHODOLOGY/APPROACH: Two workshops were organized in which
      employees predicted positive and negative effects of a Lean program. The
      workshops combined a structured brainstorm (KJ-technique) and an evaluation of
      the expected effects. Eight top managers judged the workshops' value on
      supporting decision making. FINDINGS: In total, 15 employees participated in the
      workshops. Participants from workshop 2 reported more expected effects (27
      effects; 18 positive) than from workshop 1 (14 effects; six positive). However,
      when effects were categorized, similar results were shown. Three from eight
      managers scored the results relevant for decision making and four neutral. Seven
      managers recommended future use of the instrument. Increased employee involvement
      and bottom-up thinking combined with relatively low costs were appreciated most.
      PRACTICAL IMPLICATIONS: The workshop could serve as a simple instrument to
      improve decision making and enhance successful implementation of change programs,
      as it was expected to enhance employees' involvement and was relatively easy to
      conduct and cheap. ORIGINALITY/VALUE: The workshop increased insight into
      employee views, facilitating adaptive actions by healthcare organization
      managers.

PMID- 26308404
TI  - Intensive care patient and family satisfaction.
AB  - PURPOSE: The purpose of this paper is to measure family member satisfaction with
      the care provided in an Australian private intensive care unit (ICU) at two time
      points separated by two years. The study was part of a quality improvement
      process for ICU, and was designed with reference to the revised Australian
      Commission on Safety and Quality in Health care. DESIGN/METHODOLOGY/APPROACH:
      This prospective study involved family members of patients admitted in ICU in
      February 2011 and February 2013. All patients admitted to during the study month
      were eligible. Questionnaire addressed staff competence, treatment of family,
      communication, environment and overall satisfaction, using a Likert scale. There
      was one free text question. The first survey was done by handing the survey
      package to the next of kin at the time of discharge while the second involved
      mailing a survey package within a week of discharge from ICU. Quantitative
      analysis was based on ten Likert items and qualitative analysis based on the free
      text question. FINDINGS: The response rate was 53 percent (54/102) in 2013
      (mailed) compared to 44 percent (44/100) in 2011 (hand delivered). The results
      from second (2013) survey showed statistically significant improvement in
      satisfaction associated with nursing and medical competency. Other areas with
      improvement were the relative's waiting room and visiting hours. The area lacking
      improvement was ease of finding ICU the hospital. It confirmed that families were
      satisfied with the care provided and highlighted areas for improvement. The
      results indicated high satisfaction overall, especially with the hospital staff
      competency and the overall care quality their relative received. Though most
      responses also indicated satisfaction with communication and support services,
      these areas did not perform as well. ORIGINALITY/VALUE: This study provided a
      simple and effective mechanism to monitor consumer satisfaction with ICU.

PMID- 26308405
TI  - Doctors' trustworthiness, practice orientation, performance and patient
      satisfaction.
AB  - PURPOSE: The purpose of this paper is to provide a greater understanding of the
      general practitioner (GP)-patient relationship for academics and practitioners. A
      new model for dyadic professional relationships specifically designed for
      research into the doctor-patient relationship was developed and tested. Various
      conceptual models of trust and related constructs in the literature were
      considered and assessed for their relevance as were various related scales.
      DESIGN/METHODOLOGY/APPROACH: The model was designed and tested using purposefully
      designed scales measuring doctors' trustworthiness, practice orientation
      performance and patient satisfaction. A quantitative survey used closed-ended
      questions and 372 patients responded from seven GP practices. The sample closely
      reflected the profile of the patients who responded to the DoH/NHS GP Patient
      Survey for England, 2010. FINDINGS: Hierarchical regression and partial least
      squares both accounted for 74 per cent of the variance in "overall patient
      satisfaction", the dependent variable. Trust accounted for 39 per cent of the
      variance explained, with the other independent variables accounting for the other
      35 per cent. ANOVA showed good model fit. PRACTICAL IMPLICATIONS: The findings on
      the factors which affect patient satisfaction and the doctor-patient relationship
      have direct implications for GPs and other health professionals. They are of
      particular relevance at a time of health reform and change. ORIGINALITY/VALUE:
      The paper provides: a new model of the doctor-patient relationship and
      specifically designed scales to test it; a greater understanding of the effects
      of doctors' trustworthiness, practice orientation and performance on patient
      satisfaction; and a new framework for examining the breadth and meaning of the
      doctor-patient relationship and the management of care from the patient's
      viewpoint.

PMID- 26308408
TI  - Management of the Potential Organ Donor in the ICU: Society of Critical Care
      Medicine/American College of Chest Physicians/Association of Organ Procurement
      Organizations Consensus Statement.

PMID- 26308407
TI  - Regional Perspective: The Iberoamerican Network/Council on Donation and
      Transplantation.

PMID- 26308406
TI  - Refinement and Pattern Formation in Neural Circuits by the Interaction of
      Traveling Waves with Spike-Timing Dependent Plasticity.
AB  - Traveling waves in the developing brain are a prominent source of highly
      correlated spiking activity that may instruct the refinement of neural circuits.
      A candidate mechanism for mediating such refinement is spike-timing dependent
      plasticity (STDP), which translates correlated activity patterns into changes in
      synaptic strength. To assess the potential of these phenomena to build useful
      structure in developing neural circuits, we examined the interaction of wave
      activity with STDP rules in simple, biologically plausible models of spiking
      neurons. We derive an expression for the synaptic strength dynamics showing that,
      by mapping the time dependence of STDP into spatial interactions, traveling waves
      can build periodic synaptic connectivity patterns into feedforward circuits with
      a broad class of experimentally observed STDP rules. The spatial scale of the
      connectivity patterns increases with wave speed and STDP time constants. We
      verify these results with simulations and demonstrate their robustness to likely
      sources of noise. We show how this pattern formation ability, which is analogous
      to solutions of reaction-diffusion systems that have been widely applied to
      biological pattern formation, can be harnessed to instruct the refinement of
      postsynaptic receptive fields. Our results hold for rich, complex wave patterns
      in two dimensions and over several orders of magnitude in wave speeds and STDP
      time constants, and they provide predictions that can be tested under existing
      experimental paradigms. Our model generalizes across brain areas and STDP rules,
      allowing broad application to the ubiquitous occurrence of traveling waves and to
      wave-like activity patterns induced by moving stimuli. 

PMID- 26308409
TI  - A Source of Treatment for Those Who Were (Almost) Lost: Human Immunodeficiency
      Virus-Positive to Human Immunodeficiency Virus-Positive Kidney Transplantation
      Results at 3 to 5 Years.

PMID- 26308410
TI  - Peer Review in Transplantation.

PMID- 26308411
TI  - Adibul Hasan Rizvi: Director, Sindh Institute of Urology and Transplantation
      (SIUT), Pakistan; Founder of the largest free kidney transplant program in Asia.

PMID- 26308412
TI  - Indoleamine 2,3-Dioxygenase Does It.

PMID- 26308413
TI  - Renal Function and Transplantation in Liver Disease.
AB  - Kidney injury is associated with increased morbidity and mortality in liver
      transplant recipients. Since the introduction of the model for end-stage liver
      disease for the allocation of organs for liver transplantation in 2002, the heavy
      weighting of serum creatinine in the model for end-stage liver disease score has
      significantly increased the incidence of renal dysfunction seen among patients
      undergoing liver transplantation. As a result, the frequency of simultaneous
      liver-kidney (SLK) transplantation compared to liver transplantation alone (LTA)
      has also increased. The decision to perform SLK rather than LTA is an important
      one because the benefits to the liver transplant recipient receiving a kidney
      transplant must be balanced with the benefits of using that organ for a patient
      with end-stage renal disease. However, predicting whether or not a patient with
      liver failure has reversible kidney disease, and therefore does not also need a
      kidney transplant, is difficult. The severity and duration of pretransplant renal
      dysfunction, hepatitis c, diabetes, and other risk factors for kidney disease are
      associated with an increased risk of posttransplant end-stage renal disease.
      However, there are currently no clinical findings that accurately predict renal
      recovery post liver transplant. As a result, the rate of SLK versus LTA differs
      significantly between transplant centers. To increase consistency across centers,
      multiple guidelines have been proposed to guide the decision between SLK and LTA,
      but their poor predictive value has limited their uniform adoption. Nevertheless,
      adoption of uniform rules for the allocation of kidneys would reduce the
      variability between centers in rates of SLK transplant. 

PMID- 26308414
TI  - Indoleamine 2, 3-Dioxgenase Transfected Mesenchymal Stem Cells Induce Kidney
      Allograft Tolerance by Increasing the Production and Function of Regulatory T
      Cells.
AB  - BACKGROUND: The immunoregulatory properties of mesenchymal stem cells (MSCs) have
      been well characterized in vitro. However, the role of MSCs in organ
      transplantation remains unclear. The purpose of this study was to examine the
      role of indoleamine 2, 3-dioxgenase (IDO)-transfected MSCs in immunoregulation
      both in vitro and in vivo. METHODS: Wild-type (WT) MSCs, empty lentivirus
      transfected MSCs (Lenti-MSCs) or IDO-lentivirus-transfected MSCs (IDO-MSCs) were
      cocultured with peripheral blood mononuclear cells (PBMCs) or CD4CD25 regulatory
      T (Treg) cells to examine the impact of IDO on the immunoregulatory properties of
      MSCs in vitro. WT-MSCs, Lenti-MSCs or IDO-MSCs (2 * 10/kg) were intravenously
      injected into rabbit renal transplant recipients immediately after surgery to
      examine the role of IDO-MSCs in tolerance induction in vivo. RESULTS: Lentivirus
      infection of MSCs resulted in stable expression of IDO. The IDO-MSCs inhibited
      the proliferation of CD4CD25 effector T cells to a greater extent than WT-MSCs.
      Coculture of PBMCs and IDO-MSCs induced a higher percentage of CD4CD25Foxp3 Treg
      cells in PBMCs. Additionally, the antigen-specific suppressive function of these
      CD4CD25 Treg cells was increased. The IDO-MSCs-treated Treg cells showed
      upregulated expression of cytotoxic T-lymphocyte-associated antigen 4 and
      increased secretion of IL-10 and TGF-beta. Low doses of IDO-MSCs prolonged graft
      survival and induced tolerance by inducing antigen-specific CD4CD25 Treg cells,
      as evidenced by the finding that IDO-MSCs-treated kidney transplant recipients
      accepted donor-specific skin grafts but rejected third-party grafts. CONCLUSIONS:
      The IDO increased the direct immunoregulatory properties of MSCs. The IDO-MSCs
      enhanced the expression and function of CD4CD25 Foxp3 Treg cells and induced
      allograft tolerance.

PMID- 26308415
TI  - Liver Transplantation for Hereditary Transthyretin Amyloidosis: After 20 Years
      Still the Best Therapeutic Alternative?
AB  - BACKGROUND: Until recently, liver transplantation (Ltx) was the only available
      treatment for hereditary transthyretin (TTR) amyloidosis; today, however, several
      pharmacotherapies are tested. Herein, we present survival data from the largest
      available database on transplanted hereditary TTR patients to serve as a base for
      comparison. METHODS: Liver transplantation was evaluated in a 20-year
      retrospective analysis of the Familial Amyloidosis Polyneuropathy World
      Transplant Registry. RESULTS: From April 1990 until December 2010, data were
      accumulated from 77 liver transplant centers. The Registry contains 1940
      patients, and 1379 are alive. Eighty-eight Ltx were performed in combination with
      a heart and/or kidney transplantation. Overall, 20-year survival after Ltx was
      55.3%. Multivariate analysis revealed modified body mass index, early onset of
      disease (<50 years of age), disease duration before Ltx, and TTR Val30Met versus
      non-TTR Val30Met mutations as independent significant survival factors. Early
      onset patients had an expected mortality rate of 38% that of the late-onset group
      (P < 0.001). Furthermore, Val30Met patients had an expected mortality rate of 61%
      that of non-TTR Val30Met patients (P < 0.001). With each year of duration of
      disease before Ltx, expected mortality increased by 11% (P < 0.001). With each
      100-unit increase in modified body mass index at Ltx, the expected mortality
      decreased to 89% of the expected mortality (P < 0.001). Cardiovascular death was
      markedly more common than that observed in patients undergoing Ltx for end-stage
      liver disease. CONCLUSIONS: Long-term survival after Ltx, especially for early
      onset TTR Val30Met patients, is excellent. The risk of delaying Ltx by testing
      alternative treatments, especially in early-onset TTR Val30Met patients, requires
      consideration.

PMID- 26308416
TI  - Minimal Improvement in Glomerular Filtration Rate in the First Year After Liver
      Transplantation.
AB  - BACKGROUND: Renal function is an important predictor of liver transplantation
      (LT) outcome. This study examines the change in glomerular filtration rate (GFR,
      mL/min per m) in the first year after LT, with subgroup analysis by baseline GFR,
      model for end-stage liver disease (MELD), age, sex, race, and
      diabetes/hypertension. METHODS: The records of 1275 consecutive deceased donor,
      liver, and liver/kidney transplants were reviewed retrospectively, with the
      liver/kidney data analyzed separately. Glomerular filtration rate was calculated
      using the modification of diet in renal disease equation. RESULTS: Among liver
      only patients, 25% had GFR less than 60 (mL/min per 1.73 m) at LT, and this
      increased to 39% at 1 year. There were 42% of patients with normal renal function
      (GFR > 90) at baseline, and this decreased to 18% at 1 year. Only patient
      subgroups with MELD > 25 experienced any 1-year improvement in GFR, whereas all
      lower MELD groups experienced a significant decline in GFR. At 1 year after
      transplantation, there were 42% of recipients that had an absolute GFR decrease
      greater than 20 mL/min per 1.73 m, and 39% that decreased greater than 25% from
      their transplant baseline. Only 22% had an absolute improvement in GFR greater
      than 5 mL/min per 1.73 m. CONCLUSIONS: Sixty-four percent of liver transplant
      recipients overall experience a decrease in GFR 1 year after transplantation.
      Recipients with severe kidney disease at transplant (GFR < 30) are the group most
      likely to experience improvement in GFR after transplantation. However, at 1
      year, as a group, they remain at GFR less than 60 (stage III chronic kidney
      disease). These results suggest that severe renal dysfunction may be marginally
      reversible after LT, but only 22% of the recipients in this cohort experienced
      any post-LT improvement in renal function.

PMID- 26308417
TI  - Worse Long-term Patient Survival and Higher Cancer Rates in Liver Transplant
      Recipients With a History of Smoking.
AB  - BACKGROUND: This study is a retrospective review of liver transplant (LT)
      recipients to determine the impact of tobacco exposure on 10-year survival and de
      novo cancer (CA) incidence. METHODS: The records of 1275 consecutive LT patients
      were reviewed (2001 to 2011). Patients were categorized as current, previous, or
      never smokers (NS) at listing for LT. Additionally, smokers were stratified by
      pack-years of tobacco exposure. Events included patient death, cardiovascular
      events, and de novo cancers. Cox regression analysis was used to evaluate
      survival. A complete cause of death analysis is provided, as well as a detailed
      tumor registry. RESULTS: Current (n = 279) and previous smokers (n = 323) were
      more likely to have hepatocellular carcinoma (HCC) at transplant (25%, 29% vs 18%
      [NS], P < 0.001), and these 2 groups had higher HCC recurrence rates (21%, 14% vs
      11% [NS], P = 0.18). De novo non-HCC CA was higher for current and previous
      smokers, compared to NS (18%, 16% vs 12% [NS], P = 0.05). Among those with de
      novo CA (n = 180), the 2 smoking groups were more likely to have non-skin CA
      (60%, 54% vs 27% [NS], P < 0.001). Patient survival at 10 years was worse for
      current smokers than the other study groups (55% vs 70%, P < 0.01). These results
      were largely mirrored with increased tobacco exposure. CONCLUSIONS: The LT
      outcomes are uniformly worse for patients with a history of smoking, and the risk
      of negative events increases with increasing tobacco use. Smokers have higher
      rates of HCC and recurrence, de novo cancer, and worse long-term survival.
      SUMMARY STATEMENT: This study summarizes the clinical outcomes for 1275 LT
      patients over 10 years, analyzing the impact of pre transplant recipient tobacco
      use. There are 47% of patients with a history of smoking. Because of demonstrated
      higher cancer rates and decreased survival, patients with a significant smoking
      history should be carefully scrutinized for liver transplantation.

PMID- 26308419
TI  - Hepatocellular Carcinoma Progression While on Waiting List for Liver
      Transplantation.

PMID- 26308418
TI  - Serum Antiphospholipid Antibodies in Transplanted Patients: Potential Follow-up
      Markers to Assess Pregnancy Risk?

PMID- 26308420
TI  - Sleep Disordered Breathing After Lung Transplantation: A Prospective Study.

PMID- 26308421
TI  - Robust Models Support Redistricting Liver Allocation to Reduce Geographic
      Disparity.

PMID- 26308422
TI  - The Authors' Reply.

PMID- 26308423
TI  - Ten Year Follow-up for a Patient Postmatched Unrelated Donor Bone Marrow
      Transplant Followed by Same Donor Kidney Transplant: Normal Renal Function
      Without Immunosuppression.

PMID- 26308424
TI  - Management of Tacrolimus-Telaprevir Drug-Drug Interaction in a Liver Transplant
      Patient With Hepatitis C Virus: Practical Considerations.

PMID- 26308425
TI  - Multispecialty screening, brief intervention, and referral to treatment (SBIRT)
      training in an academic medical center: Resident training experience across
      specialties.
AB  - BACKGROUND: The Substance Abuse and Mental Health Services Administration
      (SAMHSA) has recently begun to fund programs that train medical residents on how
      to utilize an evidence-based validated system known as screening, brief
      intervention, and referral to treatment (SBIRT) for providing early detection and
      brief treatment of unhealthy substance use. This paper investigates training
      outcomes of multispecialty SBIRT training at one such program at Albany Medical
      Center (AMC), one of the initial SAMHSA grantees. METHODS: Training outcomes were
      measured across 3 domains of learning: trainee satisfaction, acquired knowledge,
      and perceived usefulness. The authors explored differences in learning experience
      by postgraduate year and by specialty. RESULTS: Overall, residents were highly
      satisfied with the training, and learning outcomes met objectives. Residents'
      ratings of usefulness did not vary by program year. However, the results indicate
      that relative to residents in other programs, residents in psychiatry and
      pediatrics found the training components significantly more useful, whereas
      emergency medicine residents found training components to have less utility.
      Residents who found the training relevant to their daily work were more satisfied
      and more receptive to SBIRT training overall, which may help explain difference
      scores by program. CONCLUSIONS: Residents were highly satisfied with SBIRT skills
      training, although ratings of usefulness varied by residency program.
      Specialization by program and on-site modeling by senior faculty may enhance
      trainee satisfaction and perceived usefulness.

PMID- 26308426
TI  - The Association Between Daytime Intensivist Physician Staffing and Mortality in
      the Context of Other ICU Organizational Practices: A Multicenter Cohort Study.
AB  - OBJECTIVE: Daytime intensivist physician staffing is associated with improved
      outcomes in the ICU. However, it is unclear whether this association persists in
      the era of interprofessional, protocol-directed critical care. We sought to
      reexamine the association between daytime intensivist physician staffing and ICU
      mortality and determine if interprofessional rounding and protocols for
      mechanical ventilation in part mediate this relationship. DESIGN: Retrospective
      cohort study of ICUs in the Acute Physiology and Chronic Health Evaluation
      clinical information system from 2009 to 2010. SETTING: Forty-nine ICUs in 25
      U.S. hospitals. PATIENTS: Adults (17 yr and older) admitted to a study ICU.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We defined high-intensity
      daytime intensivist staffing as either a mandatory consult or closed ICU model;
      interprofessional rounds as rounds that included a respiratory therapist,
      pharmacist, physician and nurse; and protocol use as having protocols for
      liberation from mechanical ventilation and lung protective mechanical
      ventilation. Using multivariable logistic regression, we estimated the
      independent effect of daytime intensivist physician staffing on in-hospital
      mortality controlling for interprofessional rounds and protocols for mechanical
      ventilation, as well as other patient and hospital characteristics. Twenty-seven
      ICUs (55%) reported high-intensity daytime physician staffing, 42 ICUs (85%)
      reported daily interprofessional rounds, and 31 (63%) reported having protocols
      for mechanical ventilation. There was no association between daytime intensivist
      physician staffing and in-hospital mortality (adjusted odds ratio, 0.86; 95% CI,
      0.65-1.14). After adjusting for interprofessional rounds and protocols for
      mechanical ventilation, the effect of daytime intensivist physician staffing
      remained nonsignificant (adjusted odds ratio, 0.90; 95% CI, 0.70-1.17).
      CONCLUSION: High-intensity daytime physician staffing in the ICU was not
      significantly associated with lower mortality in a modern cohort. This
      association was not affected by interprofessional rounds or protocols for
      mechanical ventilation.

PMID- 26308427
TI  - Altered Profile of Circulating Endothelial-Derived Microparticles in Ventilator
      Induced Lung Injury.
AB  - OBJECTIVES: Pulmonary endothelial cell injury is central to the pathophysiology
      of acute lung injury. Mechanical ventilation can cause endothelial disruption and
      injury, even in the absence of preexisting inflammation. Platelet-endothelial
      cell adhesion molecule-1 is a transmembrane protein connecting adjacent
      endothelial cells. We hypothesized that injurious mechanical ventilation will
      increase circulating lung endothelial-derived microparticles, defined as
      microparticles positive for platelet-endothelial cell adhesion molecule-1, which
      could serve as potential biomarkers and mediators of ventilator-induced lung
      injury. DESIGN: Prospective randomized, controlled, animal investigation.
      SETTING: A hospital preclinical animal laboratory. SUBJECTS: Forty-eight Sprague
      Dawley rats. INTERVENTIONS: Animals were randomly allocated to one of the three
      following ventilatory protocols for 4 hours: spontaneous breathing (control
      group), mechanical ventilation with low tidal volume (6 mL/kg), and mechanical
      ventilation with high tidal volume (20 mL/kg). In both mechanical ventilation
      groups, positive end-expiratory pressure of 2 cm H2O was applied. MEASUREMENTS
      AND MAIN RESULTS: We analyzed histologic lung damage, gas exchange, wet-to-dry
      lung weight ratio, serum cytokines levels, circulating endothelial-derived
      microparticles, platelet-endothelial cell adhesion molecule-1 lung protein
      content, and immunohistochemistry. When compared with low-tidal volume mechanical
      ventilation, high-tidal volume ventilation increased lung edema score and caused
      gas-exchange deterioration. These changes were associated with a marked increased
      of circulating endothelial-derived microparticles and a reduction of platelet
      endothelial cell adhesion molecule-1 protein levels in the high-tidal volume
      lungs (p < 0.0001). CONCLUSIONS: There is an endothelial-derived microparticle
      profile associated with disease-specific features of ventilator-induced lung
      injury. This profile could serve both as a biomarker of acute lung injury and,
      potentially, as a mediator of systemic propagation of pulmonary inflammatory
      response.

PMID- 26308428
TI  - Circadian Rhythm Disruption in the Critically Ill: An Opportunity for Improving
      Outcomes.
AB  - OBJECTIVES: Circadian rhythms are severely disrupted among the critically ill.
      These circadian arrhythmias impair mentation, immunity, autonomic function,
      endocrine activity, hormonal signaling, and ultimately healing. In this review,
      we present a modern model of circadian disruption among the critically ill,
      discuss causes of these circadian arrhythmias, review observational and
      intervention studies of the effects of circadian-rhythm-restoring factors on
      medical outcomes, and identify needed key trials of circadian interventions in
      the critically ill. DATA SOURCES: MEDLINE, EMBASE, PsychINFO, Google Scholar
      through December 2014. STUDY SELECTION: Articles relevant to circadian rhythms,
      melatonin, and light in the critically ill were selected. DATA EXTRACTION AND
      DATA SYNTHESIS: Articles were synthesized for this review of circadian arrhythmia
      and the use of circadian-rhythm-restoring interventions among the critically ill.
      CONCLUSIONS: Circadian disruption often demonstrates serial degradation:
      initially, the amplitude attenuates along with delayed circadian phase. With
      increasing acuity of illness, circadian rhythmicity may be lost entirely. Causes
      of chronodisruption may be environmental or internal to the patient. In
      particular, inadequate daytime illumination and nocturnal light pollution disrupt
      healthy circadian periodicity. Internal causes of circadian arrhythmia include
      critical illness itself and subjective experience of distress and pain.
      Observational studies of windowed rooms and real-time ambient lighting have found
      that physiologic light-dark patterns may support recovery from critical illness.
      Studies of early morning bright light or evening melatonin agonists have found
      improved rates of delirium, enhanced sleep, and lower arrhythmia prevalence. The
      current evidence base emphasizes that lighting and melatoninergic interventions
      deserve to be tested in full-scale trials.

PMID- 26308429
TI  - The Impact of Tracheostomy Timing on Clinical Outcome and Adverse Events in Poor
      Grade Subarachnoid Hemorrhage.
AB  - OBJECTIVE: The value of optimal timing of tracheostomy in patients with
      subarachnoid hemorrhage is controversially debated. This study investigates
      whether early or late tracheostomy is associated with beneficial outcome or
      reduced rates of adverse events. DESIGN: Retrospective observational multicentric
      on patients prospectively inserted into a database. SETTING: Neurologic ICUs of
      one academic hospital and two secondary hospitals in Germany. PATIENTS: Data of
      all patients admitted to the Goethe University Hospital between 2006 and 2011
      with poor-grade subarachnoid hemorrhage were prospectively entered into a
      database. All patients who underwent tracheostomy were included for analysis.
      Follow-up was maintained in primary and secondary ICUs. INTERVENTIONS: Patients
      underwent tracheostomy upon expected long-term ventilation. Early tracheostomy
      was defined as performed on days 1-7 and late tracheostomy on days 8-20 after
      admission. MEASUREMENT AND MAIN RESULTS: We compared 148 consecutive patients
      admitted with poor-grade (World Federation of Neurosurgical Societies, 3-5)
      subarachnoid hemorrhage. Early tracheostomy was performed in 39 patients and late
      tracheostomy in 109 patients. In early versus late tracheostomy groups, no
      significant differences were observed with regard to ICU mortality (7.7% vs 7.3%;
      p=0.93) and median modified Rankin Scale after 6 months (3 vs 3; p=0.94). Of the
      early group, pneumonia developed in 19 patients, whereas in the late group,
      pneumonia developed in 75 patients (48.7% vs 68.8%; p=0.03; odds ratio, 2.32; 95%
      CI, 1.1-4.9). Six patients of the early group (15.4%) and 36 patients of the late
      group (33%) suffered from respiratory adverse event (p=0.04; odds ratio, 2.71;
      95% CI, 1.04-7.06). Mechanical ventilation was shorter (17.4 vs 22.3 d; p<0.05)
      and decannulation occurred earlier (42 vs 54 d; p=0.039) in the early
      tracheostomy group. CONCLUSIONS: Tracheostomy within 7 days of critical care
      admission is a feasible and safe procedure for patients with poor-grade
      subarachnoid hemorrhage. Early tracheostomy was not associated with an
      improvement in mortality or neurologic outcome but associated with fewer
      respiratory adverse events.

PMID- 26308430
TI  - Corticosteroid Therapy Benefits Septic Mice With Adrenal Insufficiency But Harms
      Septic Mice Without Adrenal Insufficiency.
AB  - OBJECTIVES: Corticosteroid therapy is frequently used in septic patients given
      the rationale that there is an increased demand for corticosteroid in sepsis, and
      up to 60% of severe septic patients experience adrenal insufficiency. However,
      the efficacy of corticosteroid therapy and whether the therapy should be based on
      the results of adrenal function testing are highly controversial. The lack of an
      adrenal insufficiency animal model and our poor understanding of the pathogenesis
      caused by adrenal insufficiency present significant barriers to address this long
      standing clinical issue. DESIGN: Prospective experimental study. SETTING:
      University laboratory. SUBJECTS: Scavenger receptor BI null and adrenal-specific
      scavenger receptor BI null mice. INTERVENTIONS: Sepsis was induced by cecal
      ligation and puncture. MEASUREMENTS AND MAIN RESULTS: Using scavenger receptor BI
      mice as the first relative adrenal insufficiency animal model, we found that
      corticosteroid therapy significantly improved the survival in cecal ligation and
      puncture-treated scavenger receptor BI mice but causes more septic death in wild
      type mice. We identified a corticosteroid cocktail that provides effective
      protection 18 hours post cecal ligation and puncture; using adrenal-specific
      scavenger receptor BI mice as an inducible corticosteroid-deficient animal model,
      we found that inducible corticosteroid specifically suppresses interleukin-6
      production without affecting tumor necrosis factor-alpha, nitric oxide, and
      interleukin-10 production. We further found that inducible corticosteroid does
      not induce peripheral lymphocyte apoptosis but promotes phagocytic activity of
      macrophages and neutrophils. CONCLUSIONS: This study demonstrates that
      corticosteroid treatment benefits mice with adrenal insufficiency but harms mice
      without adrenal insufficiency. This study also reveals that inducible
      corticosteroid has both immunosuppressive and immunopermissive properties,
      suppressing interleukin-6 production, promoting phagocytosis of immune effector
      cells, but not inducing peripheral lymphocyte apoptosis. These findings support
      our hypothesis that corticosteroid is an effective therapy for a subgroup of
      septic patients with adrenal insufficiency but harms septic patients without
      adrenal insufficiency and encourage further efforts to test this hypothesis in
      clinic.

PMID- 26308431
TI  - 23.4% Saline Decreases Brain Tissue Volume in Severe Hepatic Encephalopathy as
      Assessed by a Quantitative CT Marker.
AB  - OBJECTIVE: Cerebral edema is common in severe hepatic encephalopathy and may be
      life threatening. Bolus 23.4% hypertonic saline improves surveillance
      neuromonitoring scores, although its mechanism of action is not clearly
      established. We investigated the hypothesis that bolus hypertonic saline
      decreases cerebral edema in severe hepatic encephalopathy utilizing a
      quantitative technique to measure brain and cerebrospinal fluid volume changes.
      DESIGN: Retrospective analysis of serial CT scans, and clinical data for a case
      control series were performed. SETTING: ICUs of a tertiary care hospital.
      PATIENTS: Patients with severe hepatic encephalopathy treated with 23.4%
      hypertonic saline and control patients who did not receive 23.4% hypertonic
      saline. INTERVENTIONS: 23.4% hypertonic saline bolus administration. MEASUREMENTS
      AND MAIN RESULTS: We used clinically obtained CT scans to measure volumes of the
      ventricles, intracranial cerebrospinal fluid, and brain using a previously
      validated semiautomated technique (Analyze Direct, Overland Park, KS). Volumes
      before and after 23.4% hypertonic saline were compared with Wilcoxon signed rank
      test. Associations among total cerebrospinal fluid volume, ventricular volume,
      serum sodium, and Glasgow Coma Scale scores were assessed using Spearman rank
      correlation test. Eleven patients with 18 administrations of 23.4% hypertonic
      saline met inclusion criteria. Total cerebrospinal fluid (median, 47.6 mL [35.1
      69.4 mL] to 61.9 mL [47.7-87.0 mL]; p < 0.001) and ventricular volumes (median,
      8.0 mL [6.9-9.5 mL] to 9.2 mL [7.8-11.9 mL]; p = 0.002) increased and Glasgow
      Coma Scale scores improved (median, 4 [3-6] to 7 [6-9]; p = 0.008) after 23.4%
      hypertonic saline. In contrast, total cerebrospinal fluid and ventricular volumes
      decreased in untreated control patients. Serum sodium increase was associated
      with increase in total cerebrospinal fluid volume (r = 0.83, p < 0.001), and
      change in total cerebrospinal fluid volume was associated with ventricular volume
      change (r = 0.86; p < 0.001). CONCLUSIONS: Total cerebrospinal fluid and
      ventricular volumes increased after 23.4% hypertonic saline, consistent with a
      reduction in brain tissue volume. Total cerebrospinal fluid and ventricular
      volume change may be useful quantitative measures to assess cerebral edema in
      severe hepatic encephalopathy.

PMID- 26308432
TI  - Critical Care Medicine Beds, Use, Occupancy, and Costs in the United States: A
      Methodological Review.
AB  - This article is a methodological review to help the intensivist gain insights
      into the classic and sometimes arcane maze of national databases and
      methodologies used to determine and analyze the ICU bed supply, use, occupancy,
      and costs in the United States. Data for total ICU beds, use, and occupancy can
      be derived from two large national healthcare databases: the Healthcare Cost
      Report Information System maintained by the federal Centers for Medicare and
      Medicaid Services and the proprietary Hospital Statistics of the American
      Hospital Association. Two costing methodologies can be used to calculate U.S. ICU
      costs: the Russell equation and national projections. Both methods are based on
      cost and use data from the national hospital datasets or from defined groups of
      hospitals or patients. At the national level, an understanding of U.S. ICU bed
      supply, use, occupancy, and costs helps provide clarity to the width and scope of
      the critical care medicine enterprise within the U.S. healthcare system. This
      review will also help the intensivist better understand published studies on
      administrative topics related to critical care medicine and be better prepared to
      participate in their own local hospital organizations or regional critical care
      medicine programs. 

PMID- 26308433
TI  - Ten Myths and Misconceptions Regarding Pain Management in the ICU.
AB  - OBJECTIVES: The aim of this article is to expose common myths and misconceptions
      regarding pain assessment and management in critically ill patients that
      interfere with effective care. We comprehensively review the literature refuting
      these myths and misconceptions and describe evidence-based strategies for
      improving pain management in the ICU. DATA SOURCES: Current peer-reviewed
      academic journals, as well as standards and guidelines from professional
      societies. STUDY SELECTION: The most current evidence was selected for review
      based on the highest degree of supportive evidence. DATA EXTRACTION: Data were
      obtained via medical search databases, including OvidSP, and the National Library
      of Medicine's MEDLINE database via PubMed. DATA SYNTHESIS: After a comprehensive
      literature review, conclusions were drawn based on the strength of evidence and
      the most current understanding of pain management practices in ICU. CONCLUSIONS:
      Myths and misconceptions regarding management of pain in the ICU are prevalent.
      Review of current evidence refutes these myths and misconceptions and provides
      insights and recommendations to ensure best practices.

PMID- 26308434
TI  - Development of a Core Clinical Dataset to Characterize Serious Illness, Injuries,
      and Resource Requirements for Acute Medical Responses to Public Health
      Emergencies.
AB  - OBJECTIVES: In developed countries, public health systems have become adept at
      rapidly identifying the etiology and impact of public health emergencies.
      However, within the time course of clinical responses, shortfalls in readily
      analyzable patient-level data limit capabilities to understand clinical course,
      predict outcomes, ensure resource availability, and evaluate the effectiveness of
      diagnostic and therapeutic strategies for seriously ill and injured patients. To
      be useful in the timeline of a public health emergency, multi-institutional
      clinical investigation systems must be in place to rapidly collect, analyze, and
      disseminate detailed clinical information regarding patients across prehospital,
      emergency department, and acute care hospital settings, including ICUs. As an
      initial step to near real-time clinical learning during public health
      emergencies, we sought to develop an "all-hazards" core dataset to characterize
      serious illness and injuries and the resource requirements for acute medical
      response across the care continuum. SUBJECTS: A multidisciplinary panel of
      clinicians, public health professionals, and researchers with expertise in public
      health emergencies. DESIGN: Group consensus process. INTERVENTIONS: The consensus
      process included regularly scheduled conference calls, electronic communications,
      and an in-person meeting to generate candidate variables. Candidate variables
      were then reviewed by the group to meet the competing criteria of utility and
      feasibility resulting in the core dataset. MEASUREMENTS AND MAIN RESULTS: The 40
      member panel generated 215 candidate variables for potential dataset inclusion.
      The final dataset includes 140 patient-level variables in the domains of
      demographics and anthropometrics (7), prehospital (11), emergency department
      (13), diagnosis (8), severity of illness (54), medications and interventions
      (38), and outcomes (9). CONCLUSIONS: The resulting all-hazard core dataset for
      seriously ill and injured persons provides a foundation to facilitate rapid
      collection, analyses, and dissemination of information necessary for clinicians,
      public health officials, and policymakers to optimize public health emergency
      response. Further work is needed to validate the effectiveness of the dataset in
      a variety of emergency settings.

PMID- 26308435
TI  - An Environmental Scan for Early Mobilization Practices in U.S. ICUs.
AB  - OBJECTIVE: Early mobilization improves patient outcomes. However, diffusion of
      this intervention into standard ICU practice is unknown. Dissemination and
      implementation efforts may be guided by an environmental scan to detail readiness
      for early mobilization, current practice, and barriers to early mobilization.
      DESIGN: A telephone survey. SETTING: U.S. ICUs. SUBJECTS: Five hundred randomly
      selected U.S. ICUs stratified by regional hospital density and hospital size.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We surveyed 687 ICUs for a
      73% response rate (500 ICUs); 99% of respondents were nursing leadership. Fifty
      one percent of hospitals reported an academic affiliation. Surveyed ICUs were
      most often mixed medical/surgical (58%) or medical (22%) with a median of 16 beds
      (12-24). Thirty-four percent reported presence of a dedicated physical and/or
      occupational therapy team for the ICU. Overall, 45% of ICUs reported early
      mobilization practice; two thirds of ICUs with early mobilization practice
      reported using a written early mobilization protocol. In ICUs with early
      mobilization practice, 52% began the intervention at admission and 74% enacted
      early mobilization for both ventilated and nonventilated patients. Early
      mobilization was provided a median of 6 days per week, twice daily. Factors
      independently associated with early mobilization protocols include dedicated
      physical/occupational therapy (odds ratio, 3.34; 95% CI, 2.13-5.22; p<0.01),
      American Hospital Association region 2 (odds ratio, 3.33; 95% CI, 1.04-10.64;
      p=0.04), written sedation protocol (odds ratio, 2.36; 95% CI, 1.25-4.45; p<0.01),
      daily multidisciplinary rounds (odds ratio, 2.31; 95% CI, 1.29-4.15; p<0.01), and
      written daily goals for patients (odds ratio, 2.17; 95% CI, 1.02-4.64; p=0.04).
      Commonly cited barriers included equipment, staffing, patient and caregiver
      safety, and competing priorities. In ICUs without early mobilization adoption,
      78% have considered implementation but cite barriers including competing
      priorities and need for further planning. CONCLUSIONS: Diffusion regarding
      benefits of early mobilization has occurred, but adoption into practice is
      lagging. Mandates for multidisciplinary rounds and formal sedation protocols may
      be necessary strategies to increase the likelihood of successful early
      mobilization implementation. Methods to accurately assess and compare
      institutional performance via practice audit are needed.

PMID- 26308436
TI  - Hypoalbuminemia Within Two Postoperative Days Is an Independent Risk Factor for
      Acute Kidney Injury Following Living Donor Liver Transplantation: A Propensity
      Score Analysis of 998 Consecutive Patients.
AB  - OBJECTIVE: Acute kidney injury is a known major complication of liver
      transplantation. Previous reports have shown that hypoalbuminemia is associated
      with an increased risk of acute kidney injury. However, little is known about the
      relationship between the early postoperative albumin level and acute kidney
      injury after living donor liver transplantation. The aim of this study was to
      identify the influence of the postoperative albumin level on acute kidney injury
      prevalence after living donor liver transplantation. DESIGN: A retrospective
      analysis. SETTING: A tertiary care university hospital. PATIENTS: Nine hundred
      and ninety-eighty patients underwent living donor liver transplantation.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We divided the enrolled
      patients into two groups: group 1 included patients whose postoperative albumin
      level was less than 3.0 g/dL (n = 522), and group 2 included patients with an
      albumin level greater than or equal to 3.0 g/dL (n = 476). The prevalence of
      acute kidney injury, major adverse cardiac events, hospital stay, ICU stay, 30
      day mortality, and overall mortality was analyzed using inverse probability of
      treatment weighting and propensity-score matching (n = 249 pairs) analysis. The
      prevalence of acute kidney injury was higher in group 1 defined by both Acute
      Kidney Injury Network (after adjusting for inverse probability of treatment
      weighting [n = 364; 69.7%] and propensity-score matching [n = 152; 61.0%]) and
      Risk, Injury, Failure, Loss, and End-stage kidney disease criteria (after
      adjusting for inverse probability of treatment weighting [n = 419; 80.3%] and
      propensity-score matching [n = 190; 76.3%]). The overall mortality was higher in
      group 1 after adjusting for inverse probability of treatment weighting (n = 61;
      11.7%) and propensity-score matching (n = 23; 9.2%). The hospital (p < 0.001) and
      ICU (p = 0.006) stays were significantly prolonged in group 1. Acute kidney
      injury was associated with ICU stay by the Acute Kidney Injury Network criteria
      (p = 0.034), and overall mortality was correlated with acute kidney injury by the
      Risk, Injury, Failure, Loss, and End-stage kidney disease criteria (p = 0.014).
      CONCLUSIONS: Early postoperative hypoalbuminemia is an independent risk factor
      for acute kidney injury, and postoperative acute kidney injury is related to
      postoperative ICU stay and overall mortality after living donor liver
      transplantation.

PMID- 26308437
TI  - Prevalence of Venous Thrombosis Following Venovenous Extracorporeal Membrane
      Oxygenation in Patients With Severe Respiratory Failure.
AB  - OBJECTIVES: Venovenous extracorporeal membrane oxygenation for patients with
      severe respiratory failure is increasingly common. There has been a significant
      change in the population, technology, and approach used for venovenous
      extracorporeal membrane oxygenation over the last 10 years. The objective of this
      study is to describe the prevalence of postdecannulation deep vein thrombosis in
      the cannulated vessel in adults who have received venovenous extracorporeal
      membrane oxygenation for severe respiratory failure. DESIGN: A single-center,
      retrospective, observational cohort, electronic note review study. SETTING:
      Tertiary referral university teaching hospital. PATIENTS: Patients commenced on
      venovenous extracorporeal membrane oxygenation for severe respiratory failure.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 103 patients
      commenced on extracorporeal membrane oxygenation with 81 survivors from December
      2011 to February 2014. We performed postdecannulation venous Doppler ultrasound
      in 88.9% of extracorporeal membrane oxygenation survivors. The prevalence of deep
      vein thrombosis in the cannulated vessel following extracorporeal membrane
      oxygenation is 8.1/1,000 cannula days in patients who were screened. CONCLUSIONS:
      The prevalence of deep vein thrombosis following decannulation from
      extracorporeal membrane oxygenation for severe respiratory failure is clinically
      significant, and routine venous Doppler ultrasound following decannulation is
      warranted in this population.

PMID- 26308438
TI  - Restoration of Foxp3+ Regulatory T-cell Subsets and Foxp3- Type 1 Regulatory-like
      T Cells in Inflammatory Bowel Diseases During Anti-tumor Necrosis Factor Therapy.
AB  - BACKGROUND: A defect in regulatory T cells (Tregs) may be involved in the
      pathogenesis of inflammatory bowel diseases (IBD). Several subsets of human
      Foxp3+ Tregs (activated and resting Tregs) have now been identified, as well as
      an IL-10 and IFN-gamma double producing Foxp3 type 1 regulatory-like T cell
      (Tr1L). We have quantified these Tregs in patients with active IBD and during
      therapy with infliximab (IFX). METHODS: Blood samples were obtained from healthy
      controls (n = 54) and patients with active IBD, either before (n = 62) or during
      IFX therapy (n = 75). Tregs were identified by immunofluorescent staining and
      flow cytometry analysis. Resting and activated Foxp3+ Tregs can be differentiated
      from Foxp3+ effector T cells (Foxp3+ Teff) by the expression of CD45RA. Tr1L are
      identified as CD4+CD45RA-CD25-CD127-Foxp3- T cells. RESULTS: A numerical
      deficiency of circulating resting Tregs, activated Treg cells, and Tr1L was
      documented in patients with active IBD. Baseline levels of these Treg subsets
      predicted clinical responses to IFX. We documented an upregulation of all 3
      subsets during IFX therapy. Moreover, after therapy, significant differences in
      Treg subsets were seen between responders and nonresponders to IFX. Restoration
      of Tregs correlated with the clinical and biological response to IFX therapy.
      Trough serum levels of IFX positively correlated with the proportion of activated
      Treg cells and Tr1L during therapy. CONCLUSIONS: IFX therapy, when successful,
      results in upmodulation of the different types of Treg cells in the blood of
      patients with IBD. This effect might be relevant for understanding the mechanism
      of action of anti-TNF agents.

PMID- 26308440
TI  - Is Diffusion-weighted Magnetic Resonance Imaging for Assessing Crohn's Disease
      Ready for Prime Time? Experience with the Nancy Score.

PMID- 26308439
TI  - Clinical Value of miR-26b Discriminating Ulcerative Colitis-associated Colorectal
      Cancer in the Subgroup of Patients with Metastatic Disease.

PMID- 26308441
TI  - Multimodal Advertisement of Pregnancy in Free-Ranging Female Japanese Macaques
      (Macaca fuscata).
AB  - The role of multiple sexual signals in indicating the timing of female ovulation,
      and discrimination of this timing by males, has been particularly well studied
      among primates. However the exhibition of pregnancy signals, and how such signals
      might modulate male post-conception mating decisions, is still poorly understood.
      Here we aimed to determine if Japanese macaque males use changes in female sexual
      signals (behavioral, visual and auditory) to discriminate pregnancy and adjust
      their socio-sexual behaviors. We combined behavioral observations, digital
      photography and endocrinological (progestogen and estrogen) data, collected
      systematically during three one-month periods: the pre-conceptive period, the 1st
      month of pregnancy and the 2nd month of pregnancy. We analyzed variation in the
      probability of detecting male and female socio-sexual behaviors and estrus calls,
      as well as changes in female face color parameters, in relation to female
      reproductive state. Based on our focal observations, we found that males did not
      copulate during the pregnancy period, and that female socio-sexual behaviors
      generally decreased from the pre-conceptive to post-conceptive periods. Female
      face luminance decreased from the pre-conceptive month to the pregnancy period
      whereas face color only varied between the 1st and 2nd month of gestation. Our
      results suggest that Japanese macaque females display sexual cues of pregnancy
      that males might use to reduce energy wasted on non-reproductive copulations with
      pregnant females. We hypothesize that females advertize their pregnancy through
      changes in behavioral, visual and potential auditory signals that males can use
      to adjust their mating behaviors. We finish by discussing implications for male
      and female post-conception strategies. 

PMID- 26308442
TI  - The Principal Components of Adult Female Insole Shape Align Closely with Two of
      Its Classic Indicators.
AB  - The plantar surface of the human foot transmits the weight and dynamic force of
      the owner's lower limbs to the ground and the reaction forces back to the
      musculoskeletal system. Its anatomical variation is intensely studied in such
      fields as sports medicine and orthopedic dysmorphology. Yet, strangely, the shape
      of the insole that accommodates this surface and elastically buffers these forces
      is neither an aspect of the conventional anthropometrics of feet nor an
      informative label on the packet that markets supplementary insoles. In this paper
      we pursue an earlier suggestion that insole form in vertical view be quantified
      in terms of the shape of the foot not at the plane of support (the "footprint")
      but some two millimeters above that level. Using such sections extracted from
      laser scans of 158 feet of adult women from the University of Zagreb, in
      conjunction with an appropriate modification of today's standard geometric
      morphometrics (GMM), we find that the sectioned form can be described by its size
      together with two meaningful relative warps of shape. The pattern of this shape
      variation is not novel. It is closely aligned with two of the standard footprint
      measurements, the Chippaux-Smirak arch index and the Clarke arch angle, whose
      geometrical foci (the former in the ball of the foot, the latter in the arch) it
      apparently combines. Thus a strong contemporary analysis complements but does not
      supplant the simpler anthropometric analyses of half a century ago, with
      implications for applied anthropology. 

PMID- 26308443
TI  - Melanin Transfer in Human 3D Skin Equivalents Generated Exclusively from Induced
      Pluripotent Stem Cells.
AB  - The current utility of 3D skin equivalents is limited by the fact that existing
      models fail to recapitulate the cellular complexity of human skin. They often
      contain few cell types and no appendages, in part because many cells found in the
      skin are difficult to isolate from intact tissue and cannot be expanded in
      culture. Induced pluripotent stem cells (iPSCs) present an avenue by which we can
      overcome this issue due to their ability to be differentiated into multiple cell
      types in the body and their unlimited growth potential. We previously reported
      generation of the first human 3D skin equivalents from iPSC-derived fibroblasts
      and iPSC-derived keratinocytes, demonstrating that iPSCs can provide a foundation
      for modeling a complex human organ such as skin. Here, we have increased the
      complexity of this model by including additional iPSC-derived melanocytes.
      Epidermal melanocytes, which are largely responsible for skin pigmentation,
      represent the second most numerous cell type found in normal human epidermis and
      as such represent a logical next addition. We report efficient melanin production
      from iPSC-derived melanocytes and transfer within an entirely iPSC-derived
      epidermal-melanin unit and generation of the first functional human 3D skin
      equivalents made from iPSC-derived fibroblasts, keratinocytes and melanocytes. 

PMID- 26308445
TI  - Correction: Comparison of Bone Mineral Density between Urban and Rural Areas:
      Systematic Review and Meta-Analysis.

PMID- 26308444
TI  - Calling Biomarkers in Milk Using a Protein Microarray on Your Smartphone.
AB  - Here we present the concept of a protein microarray-based fluorescence
      immunoassay for multiple biomarker detection in milk extracts by an ordinary
      smartphone. A multiplex immunoassay was designed on a microarray chip, having
      built-in positive and negative quality controls. After the immunoassay procedure,
      the 48 microspots were labelled with Quantum Dots (QD) depending on the protein
      biomarker levels in the sample. QD-fluorescence was subsequently detected by the
      smartphone camera under UV light excitation from LEDs embedded in a simple 3D
      printed opto-mechanical smartphone attachment. The somewhat aberrant images
      obtained under such conditions, were corrected by newly developed Android-based
      software on the same smartphone, and protein biomarker profiles were calculated.
      The indirect detection of recombinant bovine somatotropin (rbST) in milk extracts
      based on altered biomarker profile of anti-rbST antibodies was selected as a real
      life challenge. RbST-treated and untreated cows clearly showed reproducible
      treatment-dependent biomarker profiles in milk, in excellent agreement with
      results from a flow cytometer reference method. In a pilot experiment, anti-rbST
      antibody detection was multiplexed with the detection of another rbST-dependent
      biomarker, insulin-like growth factor 1 (IGF-1). Milk extract IGF-1 levels were
      found to be increased after rbST treatment and correlated with the results
      obtained from the reference method. These data clearly demonstrate the potential
      of the portable protein microarray concept towards simultaneous detection of
      multiple biomarkers. We envisage broad application of this 'protein microarray on
      a smartphone'-concept for on-site testing, e.g., in food safety, environment and
      health monitoring. 

PMID- 26308446
TI  - Identification of Human N-Myristoylated Proteins from Human Complementary DNA
      Resources by Cell-Free and Cellular Metabolic Labeling Analyses.
AB  - To identify physiologically important human N-myristoylated proteins, 90 cDNA
      clones predicted to encode human N-myristoylated proteins were selected from a
      human cDNA resource (4,369 Kazusa ORFeome project human cDNA clones) by two
      bioinformatic N-myristoylation prediction systems, NMT-The MYR Predictor and
      Myristoylator. After database searches to exclude known human N-myristoylated
      proteins, 37 cDNA clones were selected as potential human N-myristoylated
      proteins. The susceptibility of these cDNA clones to protein N-myristoylation was
      first evaluated using fusion proteins in which the N-terminal ten amino acid
      residues were fused to an epitope-tagged model protein. Then, protein N
      myristoylation of the gene products of full-length cDNAs was evaluated by
      metabolic labeling experiments both in an insect cell-free protein synthesis
      system and in transfected human cells. As a result, the products of 13 cDNA
      clones (FBXL7, PPM1B, SAMM50, PLEKHN, AIFM3, C22orf42, STK32A, FAM131C, DRICH1,
      MCC1, HID1, P2RX5, STK32B) were found to be human N-myristoylated proteins.
      Analysis of the role of protein N-myristoylation on the intracellular
      localization of SAMM50, a mitochondrial outer membrane protein, revealed that
      protein N-myristoylation was required for proper targeting of SAMM50 to
      mitochondria. Thus, the strategy used in this study is useful for the
      identification of physiologically important human N-myristoylated proteins from
      human cDNA resources. 

PMID- 26308448
TI  - Replication, Communication, and the Population Dynamics of Scientific Discovery.
AB  - Many published research results are false (Ioannidis, 2005), and controversy
      continues over the roles of replication and publication policy in improving the
      reliability of research. Addressing these problems is frustrated by the lack of a
      formal framework that jointly represents hypothesis formation, replication,
      publication bias, and variation in research quality. We develop a mathematical
      model of scientific discovery that combines all of these elements. This model
      provides both a dynamic model of research as well as a formal framework for
      reasoning about the normative structure of science. We show that replication may
      serve as a ratchet that gradually separates true hypotheses from false, but the
      same factors that make initial findings unreliable also make replications
      unreliable. The most important factors in improving the reliability of research
      are the rate of false positives and the base rate of true hypotheses, and we
      offer suggestions for addressing each. Our results also bring clarity to verbal
      debates about the communication of research. Surprisingly, publication bias is
      not always an obstacle, but instead may have positive impacts-suppression of
      negative novel findings is often beneficial. We also find that communication of
      negative replications may aid true discovery even when attempts to replicate have
      diminished power. The model speaks constructively to ongoing debates about the
      design and conduct of science, focusing analysis and discussion on precise,
      internally consistent models, as well as highlighting the importance of
      population dynamics. 

PMID- 26308447
TI  - Grazing Affects Exosomal Circulating MicroRNAs in Cattle.
AB  - Circulating microRNAs (c-miRNAs) are associated with physiological adaptation to
      acute and chronic aerobic exercise in humans. To investigate the potential effect
      of grazing movement on miRNA circulation in cattle, here we profiled miRNA
      expression in centrifugally prepared exosomes from the plasma of both grazing and
      housed Japanese Shorthorn cattle. Microarray analysis of the c-miRNAs resulted in
      detection of a total of 231 bovine exosomal miRNAs in the plasma, with a constant
      expression level of let-7g across the duration and cattle groups. Expression of
      muscle-specific miRNAs such as miR-1, miR-133a, miR-206, miR-208a/b, and miR-499
      were undetectable, suggesting the mildness of grazing movement as exercise.
      According to validation by quantitative RT-PCR, the circulating miR-150 level in
      the grazing cattle normalized by the endogenous let-7g level was down-regulated
      after 2 and 4 months of grazing (P < 0.05), and then its levels in housed and
      grazing cattle equalized when the grazing cattle were returned to a housed
      situation. Likewise, the levels of miR-19b, miR-148a, miR-221, miR-223, miR-320a,
      miR-361, and miR-486 were temporarily lowered in the cattle at 1 and/or 2 month
      of grazing compared to those of the housed cattle (P < 0.05). In contrast, the
      miR-451 level was up-regulated in the grazing cattle at 2 months of grazing (P =
      0.044). The elevation of miR-451 level in the plasma was coincident with that in
      the biceps femoris muscle of the grazing cattle (P = 0.008), which suggests the
      secretion or intake of miR-451 between skeletal muscle cells and circulation
      during grazing. These results revealed that exosomal c-miRNAs in cattle were
      affected by grazing, suggesting their usefulness as molecular grazing markers and
      functions in physiological adaptation of grazing cattle associated with
      endocytosis, focal adhesion, axon guidance, and a variety of intracellular
      signaling, as predicted by bioinformatic analysis. 

PMID- 26308449
TI  - Investigation of Anthrax Cases in North-East China, 2010-2014.
AB  - We determined the genotypes of seven Bacillus anthracis strains that were
      recovered from nine anthrax outbreaks in North-East China from 2010 to 2014, and
      two approved vaccine strains that are currently in use in China. The causes of
      these cases were partly due to local farmers being unaware of the presence of
      anthrax, and butchers with open wounds having direct contact with anthrax
      contaminated meat products. The genotype of five of the seven recovered strains
      was A.Br.001/002 sub-lineage, which was concordant with previously published
      research. The remaining two cases belongs to the A.Br.Ames sub-lineage. Both of
      these strains displayed an identical SNR pattern, which was the first time that
      this genotype was identified in North-East China. Strengthening education in
      remote villages of rural China is an important activity aimed at fostering
      attempts to prevent and control anthrax. The genotype of the vaccine strain
      Anthrax Spore Vaccine No.II was A.Br.008/009 and A.Br.001/002 for the vaccine
      strain Anthrax Spore Vaccine Non-capsulated. Further studies of their
      characteristics are clearly warranted. 

PMID- 26308450
TI  - A Novel Low-Ringing Monocycle Picosecond Pulse Generator Based on Step Recovery
      Diode.
AB  - This paper presents a high-performance low-ringing ultra-wideband monocycle
      picosecond pulse generator, formed using a step recovery diode (SRD), simulated
      in ADS software and generated through experimentation. The pulse generator
      comprises three parts, a step recovery diode, a field-effect transistor and a
      Schottky diode, used to eliminate the positive and negative ringing of pulse.
      Simulated results validate the design. Measured results indicate an output
      waveform of 1.88 peak-to-peak amplitude and 307ps pulse duration with a minimal
      ringing of -22.5 dB, providing good symmetry and low level of ringing. A high
      degree of coordination between the simulated and measured results is achieved. 

PMID- 26308452
TI  - [What I Don't Know Now, Can't Give me "Know How"...].

PMID- 26308451
TI  - 1,25-Dihydroxyvitamin D to PTH(1-84) Ratios Strongly Predict Cardiovascular Death
      in Heart Failure.
AB  - OBJECTIVES: Vitamin D deficiency and hyperparathyroidism are common in patients
      with heart failure (HF). There is a growing body of evidence supporting the role
      of vitamin D and parathyroid hormone (PTH) in cardiac remodeling and worsening of
      HF. Lack of reliable automated testing of 1,25-dihydroxyvitamin D (1,25(OH)2D),
      the biologically active metabolite of vitamin D, has limited its contribution to
      the prognostic assessment of HF. Here, the association of 1,25(OH)2D and PTH(1
      84) levels was evaluated for prediction of cardiovascular death in chronic HF
      patients. METHODS: We conducted a single center prospective cohort including 170
      chronic HF patients (females n = 36; males n = 134; NYHA II-IV; mean age: 67
      years; etiology: ischemic n = 119, dilated cardiomyopathy n = 51; mean LVEF:
      23%). The primary outcome was cardiovascular death. RESULTS: Serum levels of
      1,25(OH)2D decreased markedly with increased HF severity. Medians were 33.3 pg/mL
      for NYHA-II patients, 23.4 pg/mL for NYHA-III, and 14.0 pg/mL for NYHA-IV
      patients (p<0.001). Most patients had levels of 25(OH)D below 30ng/mL, and
      stratification by NYHA functional class did not show significant differences (p =
      0.249). The 1,25(OH)2D to PTH(1-84) ratio and the (1,25(OH)2D)2 to PTH(1-84)
      ratio were found to be the most significantly related to HF severity. After a
      median follow-up of 4.1 years, 106 out of 170 patients reached the primary
      endpoint. Cox proportional hazard modeling revealed 1,25(OH)2D and the 1,25(OH)2D
      to PTH(1-84) ratios to be strongly predictive of outcomes. CONCLUSIONS:
      1,25(OH)2D and its ratios to PTH(1-84) strongly and independently predict
      cardiovascular mortality in chronic HF.

PMID- 26308453
TI  - [Psychoeducation is an Outdated Paternalistic Concept - Pro].

PMID- 26308454
TI  - [Psychoeducation is an Outdated Paternalistic Concept - Contra].

PMID- 26308455
TI  - [Which Factors Influence the Success of Supported Employment?].
AB  - OBJECTIVES: Main goal of this review is to identify predictive factors for the
      outcome of Individual Placement and Support (IPS) with a focus on Supported
      Employment (SE) and of pre-vocational training (PVT) of individuals with mental
      illness. METHOD: A systematic search of PsychInfo, PubMed, PsychIndex and
      PsyArticles was conducted. Studies were included if they compared both
      approaches, SE and PVT, contained predictors to optimize SE or PVT, investigated
      the effectiveness of SE or examined what constitutes adequate job coaching.
      RESULTS: 45 articles have been included. 27 articles referred to predictors that
      influence the outcome of SE or PVT, 9 showed a direct comparison between both
      approaches, 5 investigated job coaching and 4 examined the effectiveness of SE.In
      summary motivation, work experience and high fidelity of IPS criteria seem to be
      the most important predictors for a successful job reintegration using SE.
      DISCUSSION: Overall, SE is more effective than PVT. The success of SE can be
      enhanced by keeping the predictors in mind. However, future research should focus
      more specifically on predictors.

PMID- 26308456
TI  - [Psychoeducation in Depression: Results of two Surveys five Years Apart in
      Germany, Austria and Switzerland].
AB  - OBJECTIVE: Studies investigating the frequency of psychoeducation in depression
      for patients and their family members in hospital settings and assessing how
      psychoeducation is offered are lacking. METHODS: Two postal surveys were done
      five years apart addressing these questions to the heads of all psychiatric
      hospitals in Germany, Austria and Switzerland. RESULTS: 67 % of the participating
      hospitals offered psychoeducation in depression. 60 % of the patients treated in
      the hospitals participated in psychoeducation groups, whereas only 13 % of the
      family members did. In the mean, a single psychoeducational session lasted for 61
      minutes (SD = 14), took place 1.4-times per week (SD = 0.5) and there were 7.4
      sessions (SD = 2.8). 56 % of the moderators of the psychoeducational groups used
      a published manual for conducting the groups. CONCLUSION: The frequency of
      offering psychoeducation in depression for patients is almost comparable to that
      in schizophrenia. However, there is still room for improvement, especially when
      it comes to family psychoeducation in depression where all efforts need to be
      done to increase the number of groups offered in order to inform more families
      and help them coping with depression.

PMID- 26308457
TI  - [Neuropsychological Functioning as a Predictor of Treatment Response to
      Psychoeducational, Cognitive Behavioral Therapy in People at Clinical High Risk
      of First Episode Psychosis].
AB  - OBJECTIVE: Investigate whether treatment response in people at clinical high risk
      of psychosis (CHR) is predicted by their cognitive performance. METHOD: 128 CHR
      outpatients were randomized into two treatment groups, one receiving integrated
      psychological intervention (IPI), including psychoeducation, the other receiving
      supportive counselling (SC) for 12 months. Multiple regression analysis was used
      to identify neurocognitive predictors of treatment response in a subgroup of n =
      105, measured by symptomatic and functional improvement at 1-year follow-up.
      RESULTS: In the IPI, treatment response was associated with performance of
      executive control and processing speed (R2 = 0.27, p = 0.002). In both treatment
      groups, performance of working memory/attention was a significant predictor (IPI:
      R2 = 0.15, p = 0.039, SC: R2 = 0.19, p = 0.012). CONCLUSION: Cognitive
      performance is associated with treatment response in CHR people. The enhancement
      of cognitive performance is a useful target of early intervention.

PMID- 26308458
TI  - [New Paradigms? Current Trends within National and International Psychotherapy
      Research].
AB  - This article is devoted to the question which paradigms currently determine
      psychotherapy and psychotherapy research, and if there are indicators of paradigm
      changes in this field. The question of the efficacy and effectiveness (including
      the effectiveness of a transfer of psychotherapeutic knowledge to service) is
      specifically focussed as well as the question of the central therapeutic factors
      and the significance of the person of the therapist. It is argued that there are
      really some signals of a paradigm switch, with a turn away from controlled
      outcome research, representing only a minor part of patients in need of
      psychotherapy, towards a more specific process oriented research, also
      considering differential effects of the therapist. The most prominent indicator
      of a paradigm change is reflected by an increasing influence of patient oriented
      psychotherapy research which - consequently - should also be supported by the
      insurances as well as the funding organisations. 

PMID- 26308461
TI  - DNA Methylation Dynamics Regulate the Formation of a Regenerative Wound
      Epithelium during Axolotl Limb Regeneration.
AB  - The formation of a blastema during regeneration of an axolotl limb involves
      important changes in the behavior and function of cells at the site of injury.
      One of the earliest events is the formation of the wound epithelium and
      subsequently the apical epidermal cap, which involves in vivo dedifferentiation
      that is controlled by signaling from the nerve. We have investigated the role of
      epigenetic modifications to the genome as a possible mechanism for regulating
      changes in gene expression patterns of keratinocytes of the wound and blastema
      epithelium that are involved in regeneration. We report a modulation of the
      expression DNMT3a, a de novo DNA methyltransferase, within the first 72 hours
      post injury that is dependent on nerve signaling. Treatment of skin wounds on the
      upper forelimb with decitabine, a DNA methyltransferase inhibitor, induced
      changes in gene expression and cellular behavior associated with a regenerative
      response. Furthermore, decitabine-treated wounds were able to participate in
      regeneration while untreated wounds inhibited a regenerative response.
      Elucidation of the specific epigenetic modifications that mediate cellular
      dedifferentiation likely will lead to insights for initiating a regenerative
      response in organisms that lack this ability. 

PMID- 26308462
TI  - Hypoxia Affects Nitrogen Uptake and Distribution in Young Poplar (Populus *
      canescens) Trees.
AB  - The present study with young poplar trees aimed at characterizing the effect of
      O2 shortage in the soil on net uptake of NO3- and NH4+ and the spatial
      distribution of the N taken up. Moreover, we assessed biomass increment as well
      as N status of the trees affected by O2 deficiency. For this purpose, an
      experiment was conducted in which hydroponically grown young poplar trees were
      exposed to hypoxic and normoxic (control) conditions for 14 days. 15N-labelled
      NO3- and NH4+ were used to elucidate N uptake and distribution of currently
      absorbed N and N allocation rates in the plants. Whereas shoot biomass was not
      affected by soil O2 deficiency, it significantly reduced root biomass and,
      consequently, the root-to-shoot ratio. Uptake of NO3- but not of NH4+ by the
      roots of the trees was severely impaired by hypoxia. As a consequence of reduced
      N uptake, the N content of all poplar tissues was significantly diminished. Under
      normoxic control conditions, the spatial distribution of currently absorbed N and
      N allocation rates differed depending on the N source. Whereas NO3- derived N was
      mainly transported to the younger parts of the shoot, particularly to the
      developing and young mature leaves, N derived from NH4+ was preferentially
      allocated to older parts of the shoot, mainly to wood and bark. Soil O2
      deficiency enhanced this differential allocation pattern. From these results we
      assume that NO3- was assimilated in developing tissues and preferentially used to
      maintain growth and ensure plant survival under hypoxia, whereas NH4+ based N was
      used for biosynthesis of storage proteins in bark and wood of the trees. Still,
      further studies are needed to understand the mechanistic basis as well as the eco
      physiological advantages of such differential allocation patterns. 

PMID- 26308463
TI  - Comparative evaluation of gel column agglutination and erythrocyte magnetized
      technology for red blood cell alloantibody titration.
AB  - Antibody titration is traditionally performed using a conventional test tube
      (CTT) method, which is subjected to interlaboratory variations because of a lack
      of standardization and reproducibility. The aim of this study is to compare newer
      methods such as get column technology (GCT) and erythrocyte magnetized technology
      (EMT) for antibody titration in terms of accuracy and precision. Patient serum
      samples that contained immunoglobin G (IgG) red blood cell (RBC) alloantibodies
      of a single specificity for Rh or K anitgens were identified during routine
      transfusion service testing and stored. Titration and scoring were performed
      separately by and stored. Titration and scoring were performed separately by
      different laboratory personnel on CTT, GCT, and EMT. Testing was performed a
      total of three times on each sample. Results were analyzed for accuracy and
      precision. A total of 50 samples were tested. Only 20 percent of samples tested
      with GCT shoed titers identical to CTT, whereas 48 percent of samples tested with
      EMT showed titers identical to CTT. Overall, the mean of th titer difference from
      CTT was higher using GCT (+0.31) compared with that using EMT (+0.13). Precision
      shown by CTT was 30 percent, EMT was 76 percent, and GCT was 92 percent on repeat
      testing. GCT showed higher titer values in comparison with CTT but was found to
      be the most precise. EMT titers were comparable to CTT, and its precision was
      intermediate. Further studies to validate this method are required.

PMID- 26308464
TI  - High-resolution melting analysis as an alternative method for human neutrophil
      antigen genotyping.
AB  - Human neutrophil antigen (HNA)-typed granulocyte panels are widely used to screen
      for the presence of HNA antibodies and to determine antibody specificity. Many
      laboratories screen donors for HNA genotypes using low-throughput methods such as
      allele-specific polymerase chain reaction (PCR), PCR-restriction fragment-length
      polymorphism, and multiplex PCR. In the present study, we used a high-resolution
      melting (HRM) analysis to determine HNA genotypes. For the HRM analysis, purified
      genomic DNA samples were amplified via PCR with HNA-specific primers. Nucleotide
      substitutions in genes encoding HNAs were differentiated on the basis of the HRM
      curves, and the results of HRM and DNA sequencing analyses were determined to be
      in complete agreement. The gene frequency of HNA-1a, -1b, -1c, -3a, -3b, -4a, 
      4b, -5a, and -5b in the Japanese population was consistent with the previous
      reports. Our results suggest that HRM analysis can be used for genotyping HNA
      antigens determined by single nucleotide substitutions.

PMID- 26308465
TI  - Kell and Kx blood group systems.
AB  - The Kell and Kx blood group systems are expressed as covalently linked molecules
      on red blood cells (RBCs). The Kell blood group system is very polymorphic, with
      35 antigens assigned to the system. The expression of Kell glycoprotein on RBCs
      is not critical to the erythrocyte function. However, the expression of KX is
      critical to normal morphology, and null mutations are associated with the McLeod
      neuroacanthocytosis syndrome. The immunogenicity of the K anigen is second only
      to the D anigen, and alloantibodies to Kell anigens can cause transfusion
      reactions and hemolytic disease of the fetus and newborn. Kell alloantibodies in
      pregnancy are known to suppress erythropoiesis, which can result in serious
      disease despite low amniotic bilirubin levels and low antibody titers. Late-onset
      anemia with reticulocytopenia is thought to be attributable to the continual
      suppression of erythropoiesis from residual alloantibody in the infant.
      Alloimmunization to XK protein is rare, and expressed polymorphisms have not been
      reported. Together these two blood group systems share an integral relationship
      in transfusion medicine, neurology, and musculoskeletal biology.

PMID- 26308466
TI  - A simple approach to screen rare donors in Brazil.
AB  - Providing blood units for patients with an antibody to a high-prevalence antigen
      or with multiple common antibodies is a constant challenge to the blood banks.
      Finding a compatible donor requires extensive screening, with incurs a large
      amount of investment. In this article, we share our experience of organizing a
      rare donor inventory with limited resources, we include the strategy used for
      finding rare donors, and we share the difficulties found during the
      implementation of the approach and the results obtained.

PMID- 26308467
TI  - Proposed criterion for distinguishing ABO mosaics from ABO chimeras using flow
      cytometric analysis.
AB  - Differentiation of ABO mosaics from chimeras is performed using flow cytometry
      (FCM) analysis. Although mosaics and chimeras have been distinguished by presence
      or absence of clear resolution using FCM analysis, the lack of quantitative
      metrics and definitive criteria for this differentiation has made some cases
      difficult to differentiate. In this study, therefore, we attempted to establish a
      definitive and quantitative criterion for this differentiation. When FCM
      histogram gates for group "A" or "B" antigen-negative and -positive red blood
      cells (RBCs) were set such that group O RBCs were classified as 99 percent
      negative and group A or B RBCs as 99 percent positive, the percentages of RBCs in
      the middle region of six chimeras and 23 mosaics (12 A mosaics and 11 B mosaics)
      were 0.1-0.6 percent and 7.0-19.0 percent, respectively. This results suggested
      that ABO mosaics and chimeras can be unambiguously differentiated when the cutoff
      point of the intermediate region is set to 1 percent.

PMID- 26308468
TI  - Kidd blood group system: a review.
AB  - The Kidd blood group system has been recognized as clinically important in red
      blood cell (RBC) serology since its identification in 1951. Forty years later,
      the JK glycoprotein was determined to be a product of SCL14A1 and was identical
      to the urea transport protein UT-B produced by HUT11A. The functional role of the
      protein as a urea transporter in RBC and kidney has been well documented. The
      polymorphism responsible for the antithetical anigens Jk(a) and Jk(b) was
      identified in 1994 as c.838G>A (p.Asp280Asn). Recent discoveries have expanded
      the system to include 23 variant alleles recognized by the International Society
      of Blood Transfusion that silence the protein expression and 7 variant alleles
      presumably producting weak or partia JK antigens. Null phenotypes have been
      identified in individuals of several populations including those of African,
      Indian, and Chinese decent, in addition to the well-documented findings in the
      Polynesian and Finnish populations. This review will examine the historical
      information about the anigens and antibodies of the JK system as well as catalog
      the variations of the JK gene.

PMID- 26308469
TI  - Distribution, migration and potential risk of heavy metals in the Shima River
      catchment area, South China.
AB  - The distribution, migration and potential risk of heavy metals in water and soil
      environments, related to city water supply, were investigated. Heavy metal
      concentrations in waters from the Shima River water ranged from not detected
      (n.d.) to 749 MUg L(-1) for Mn, n.d. to 151 MUg L(-1) for Ni, 7.00 to 494 MUg L(
      1) for Zn, n.d. to 93.0 MUg L(-1) for Cu and n.d. to 9860 MUg L(-1) for Fe. The
      highest concentration of heavy metals was found at an upstream site in February
      as a result of industrial effluent discharge. Groundwater (GW1-GW5) and soil (S1
      S8) samples along the riverbank showed similar levels of contamination due to a
      close hydraulic relationship and frequent exchange of water, probably resulting
      in migration of heavy metals from river water to the aquifer and accumulation at
      the interface. The mean concentrations of heavy metals in soil profiles were in
      the ranges of 2.50-19.0 mg kg(-1) for As, 2.80-11.2 mg kg(-1) for Cd, 20.3-165 mg
      kg(-1) for Cr, 14.5-298 mg kg(-1) for Cu, 11.4-102 mg kg(-1) for Ni, 7.00-95.0 mg
      kg(-1) for Pb, 40.4-465 mg kg(-1) for Zn, 8.80 * 10(3)-21.8 * 10(3) mg kg(-1) for
      Fe, and 62.2-430 mg kg(-1) for Mn, showing severe soil pollution by Cd. LUMISTox
      testing and the potential ecological risk index (RI) were used to assess the
      potential for adverse ecological effects caused by heavy metals in water and soil
      media. River water samples posed slight acute toxicity to Vibrio fischeri with
      luminescence inhibition rates (LIRs) ranging from 24.6% to 38.4% in February.
      Elevated Zn and Cu concentrations significantly contributed to the toxicity.
      However, groundwater did not exhibit any toxicity to Vibrio fischeri. The
      severity of the potential ecological risk for individual metals (Er(i)) decreased
      in the order of Cd > Cu > Ni > As > Pb > Zn > Cr. RI values indicated that all
      soil samples in the study area posed a high level of ecological risk. Cd
      contributed significantly (95.5-98.9%) to potential ecological risk in soils.

PMID- 26308470
TI  - Formation of long single quantum dots in high quality InSb nanowires grown by
      molecular beam epitaxy.
AB  - We report on realization and transport spectroscopy study of single quantum dots
      (QDs) made from InSb nanowires grown by molecular beam epitaxy (MBE). The
      nanowires employed are 50-80 nm in diameter and the QDs are defined in the
      nanowires between the source and drain contacts on a Si/SiO2 substrate. We show
      that highly tunable QD devices can be realized with the MBE-grown InSb nanowires
      and the gate-to-dot capacitance extracted in the many-electron regimes is scaled
      linearly with the longitudinal dot size, demonstrating that the devices are of
      single InSb nanowire QDs even with a longitudinal size of ~700 nm. In the few
      electron regime, the quantum levels in the QDs are resolved and the Landeg
      factors extracted for the quantum levels from the magnetotransport measurements
      are found to be strongly level-dependent and fluctuated in a range of 18-48. A
      spin-orbit coupling strength is extracted from the magnetic field evolutions of a
      ground state and its neighboring excited state in an InSb nanowire QD and is on
      the order of ~300 MUeV. Our results establish that the MBE-grown InSb nanowires
      are of high crystal quality and are promising for the use in constructing novel
      quantum devices, such as entangled spin qubits, one-dimensional Wigner crystals
      and topological quantum computing devices. 

PMID- 26308471
TI  - Correction: State-of-the-art strategies for targeting protein-protein
      interactions by small-molecule inhibitors.
AB  - Correction for 'State-of-the-art strategies for targeting protein-protein
      interactions by small-molecule inhibitors' by Chunquan Sheng et al., Chem. Soc.
      Rev., 2015, DOI: 10.1039/c5cs00252d. 

PMID- 26308472
TI  - Safety of cochlear implantation before 12 months of age: Medical University of
      South Carolina and Pediatric American College of Surgeons-National Surgical
      Quality improvement program outcomes.
AB  - OBJECTIVES/HYPOTHESIS: The primary objective of this study was to determine the
      safety profile of cochlear implantation (CI) in infants <12 months old. STUDY
      DESIGN: Retrospective review of institutional (Medical University of South
      Carolina [MUSC]) and national data (Pediatric American College of Surgeons
      National Surgical Quality Improvement Program [ACS-NSQIP]). METHODS: Cases were
      subdivided into two groups according to age at CI: <12 months and 12 to 18
      months. The primary outcome measure of interest was occurrence of a postoperative
      medical or surgical complication. Operative time, anesthesia time, time in the
      postoperative anesthesia care unit, and length of stay were also assessed.
      RESULTS: In infants <12 months of age, the incidence of a 30-day postoperative
      surgical complication using the ACS-NSQIP database was 3.6%; this did not differ
      from the rate observed in the 12- to 18-month-old group (3.2%, P = 1.0). In the
      MUSC series, the occurrence of a 30-day postoperative complication in children
      <12 months old was comparable (2.7%). At longer-term follow-up (mean = 3.7
      years), the incidence of a postoperative surgical complication in infants <12
      months old using MUSC data was 13.5%. When compared to older children at longer
      term follow-up, no difference was noted (12.7%, P = 1.0). The incidence of a
      postoperative medical or anesthetic complication in children <12 months of age
      was extremely rare in both MUSC and ACS-NSQIP series (0% and 1.3%, respectively).
      CONCLUSIONS: Institutional and national data demonstrate that CI in children <12
      months of age is a safe procedure. Although infants <12 months old are at risk
      for postoperative complications, the rates of surgical and medical complications
      were no different compared to children 12 to 18 months of age. LEVEL OF EVIDENCE:
      4 Laryngoscope, 126:707-712, 2016.

PMID- 26308473
TI  - Advanced Therapeutic Dressings for Effective Wound Healing--A Review.
AB  - Advanced therapeutic dressings that take active part in wound healing to achieve
      rapid and complete healing of chronic wounds is of current research interest.
      There is a desire for novel strategies to achieve expeditious wound healing
      because of the enormous financial burden worldwide. This paper reviews the
      current state of wound healing and wound management products, with emphasis on
      the demand for more advanced forms of wound therapy and some of the current
      challenges and driving forces behind this demand. The paper reviews information
      mainly from peer-reviewed literature and other publicly available sources such as
      the US FDA. A major focus is the treatment of chronic wounds including
      amputations, diabetic and leg ulcers, pressure sores, and surgical and traumatic
      wounds (e.g., accidents and burns) where patient immunity is low and the risk of
      infections and complications are high. The main dressings include medicated moist
      dressings, tissue-engineered substitutes, biomaterials-based biological
      dressings, biological and naturally derived dressings, medicated sutures, and
      various combinations of the above classes. Finally, the review briefly discusses
      possible prospects of advanced wound healing including some of the emerging
      physical approaches such as hyperbaric oxygen, negative pressure wound therapy
      and laser wound healing, in routine clinical care.

PMID- 26308474
TI  - Unfolding and folding pathway of lysozyme induced by sodium dodecyl sulfate.
AB  - Proteins may exhibit an unfolding or folding state in the presence of a
      surfactant. In the present study, the unfolding and folding pathway of hen egg
      white lysozyme (HEWL) induced by sodium dodecyl sulfate (SDS) is studied. The
      stoichiometry obtained from isothermal titration calorimetry (ITC) provides
      guidelines for other techniques. The fluorescence spectra and circular dichroism
      show that the fluorescence properties and secondary structure of proteins undergo
      a two-step change upon binding with SDS, in which the intensity decreases, the
      emission blue shifts and the helical conformation decreases at low ratios of SDS
      to HEWL, while all of them return to the native-like state upon the addition of
      SDS at higher ratios. At the end of the binding, HEWL presents a higher alpha
      helical content but its tertiary structure is lost compared to its native state,
      which is namely a molten globule state. Small angle X-ray scattering (SAXS)
      analysis and the derived model reveal that the complexes possess a decorated core
      shell structure, with the core composed of dodecyl chains and the shell
      consisting of SDS head groups with a protein in molten globule state. Five
      binding steps, including the individual details involved in the denaturation,
      were obtained to describe the unfolding and folding pathway of HEWL induced by
      SDS. The results of this study not only present details about the denaturation of
      protein induced by SDS and the structure of the complexes involved in each
      binding step, but also provide molecular insights into the mechanism of the
      higher helical conformation of proteins in the presence of surfactant micelles. 

PMID- 26308475
TI  - Insulin resistance in bipolar disorder: relevance to routine clinical care.

PMID- 26308476
TI  - Primary care weight loss maintenance with behavioral nutrition: An observational
      study.
AB  - OBJECTIVE: To evaluate the rate of weight loss maintenance, defined as a 10% loss
      of initial weight maintained beyond 1 year, among patients with BMI > 25 kg/m(2)
      who had been managed by primary care physicians practicing behavioral nutrition
      (moderately high-protein diet, carbohydrate restriction, and behavioral therapy).
      METHODS: Restrospective analysis of anthropometric characteristics, weight loss,
      and its determinants was conducted in 14,256 patients. RESULTS: 26.7% of subjects
      met the success criterion (successful maintenance group; SM), 25.7% did not
      maintain their weight loss (unsuccessful maintenance group; UM), and 47.6% did
      not lose 10% of their initial weight (failure group; F). At inclusion, patients
      in the SM group had a greater BMI and fat mass percentage (40.5% in SM, 38.5% in
      UM, and 37.0% in F). These patients lost more weight (-14.1% vs. -4.59%) and fat
      mass (-24.7% vs. -8.21%) than patients in the UM group, and contribution of
      adiposity to their weight loss was 75.1%. Follow-up of patients in the SM group
      was characterized by a greater frequency of consultations. CONCLUSIONS:
      Management by primary care providers with behavioral nutrition facilitates weight
      loss maintenance in patients with overweight and obesity. The determinants of
      success are frequency of consultations, initial BMI, and initial weight loss.

PMID- 26308477
TI  - Meta-analysis of the relationship between breaks in sedentary behavior and
      cardiometabolic health.
AB  - OBJECTIVE: The concept of "breaks" in sedentary behavior has emerged as a
      potential modifier of detrimental effects on adiposity caused by sedentary
      behavior. The existing research investigating the relationship between breaks in
      sedentary behavior with adiposity and cardiometabolic health in adults was
      systematically reviewed and quantitatively synthesized by this study. METHODS:
      Observational and experimental studies that examined the relationships between
      the frequency of interruptions of sedentary behavior and markers of adiposity and
      cardiometabolic health in adults were identified by a systematic search of the
      literature. A meta-analysis was conducted by using the inverse variance method
      for experimental trials and a Bayesian posterior probability of existence of an
      association between breaks with adiposity and cardiometabolic markers for
      observational studies. RESULTS: It was revealed by the pooled results from nine
      experimental studies that breaks in sedentary periods of at least light intensity
      may have a positive effect on glycemia but not on lipidemia for adults. It is
      unclear whether this effect is independent of total sitting time. However, the 10
      identified observational studies showed an association with breaks, which was
      independent of total sedentary time, but only for obesity metrics. CONCLUSIONS:
      The theory that interrupting bouts of sedentary behavior with light-intensity
      activity might help control adiposity and postprandial glycemia was supported by
      the evidence. Further investigations with better methods of measuring sedentary
      behavior patterns and improved study designs are necessary to confirm this
      preliminary evidence.

PMID- 26308478
TI  - Gene expression in WAT from healthy humans and monkeys correlates with FGF21
      induced browning of WAT in mice.
AB  - OBJECTIVE: Identify a gene expression signature in white adipose tissue (WAT)
      that reports on WAT browning and is associated with a healthy phenotype. METHODS:
      RNA from several different adipose depots across three species were analyzed by
      whole transcriptome profiling, including 1) mouse subcutaneous white fat, brown
      fat, and white fat after in vivo treatment with FGF21; 2) human subcutaneous and
      omental fat from insulin-sensitive and insulin-resistant patients; and 3) rhesus
      monkey subcutaneous fat from healthy and dysmetabolic individuals. RESULTS: A
      "browning" signature in mice was identified by cross-referencing the FGF21
      induced signature in WAT with the brown adipose tissue (BAT) vs. WAT comparison.
      In addition, gene expression levels in WAT from insulin-sensitive/healthy vs.
      insulin-resistant/dysmetabolic humans and rhesus monkeys, respectively,
      correlated with the gene expression levels in mouse BAT vs. WAT. A subset of 49
      genes were identified that were consistently regulated or differentially
      expressed in the mouse and human data sets that could be used to monitor browning
      of WAT across species. CONCLUSIONS: Gene expression profiles of WATs from healthy
      insulin-sensitive individuals correlate with those of BAT and FGF21-induced
      browning of WAT.

PMID- 26308479
TI  - The effect of differing patterns of childhood body mass index gain on adult
      physiology in American Indians.
AB  - OBJECTIVE: Identifying groups of individuals with similar patterns of body mass
      index (BMI) change during childhood may increase understanding of the
      relationship between childhood BMI and adult health. METHODS: Discrete classes of
      BMI z-score change were determined in 1,920 American Indian children with at
      least four non diabetic health examinations between the ages of 2 and 18 years
      using latent class trajectory analysis. In subsets of subjects, data were
      available for melanocortin-4 receptor (MC4R) sequencing; in utero exposure to
      type 2 diabetes (T2D); or, as adults, oral glucose tolerance tests, onset of T2D,
      or body composition. RESULTS: Six separate groups were identified. Individuals
      with a more modern birth year, an MC4R mutation, or in utero exposure to T2D were
      clustered in the two groups with high increasing and chronic overweight z-scores
      (P < 0.0001). The z-score classes predicted adult percent fat (P < 0.0001,
      partial r(2)  = 0.18 adjusted for covariates). There was a greater risk for T2D,
      independent from adult BMI, in three classes (lean increasing to overweight, high
      increasing, and chronic overweight z-scores) compared to the two leanest groups
      (respectively: HRR= 3.2, P = 0.01; 6.0, P = 0.0003; 11.6, P < 0.0001).
      CONCLUSIONS: Distinct patterns of childhood BMI z-score change associate with
      adult adiposity and may impact risk of T2D.

PMID- 26308481
TI  - Design strategy for 25% external quantum efficiency in green and blue thermally
      activated delayed fluorescent devices.
AB  - Carbazole- and triazine-derived thermally activated delayed fluorescent (TADF)
      emitters, with three donor units and an even distribution of the highest occupied
      molecular orbital, achieve high external quantum efficiencies of above 25% in
      blue and green TADF devices. 

PMID- 26308480
TI  - Gender- and race-specific metabolic score and cardiovascular disease mortality in
      adults: A structural equation modeling approach--United States, 1988-2006.
AB  - OBJECTIVE: Consider all metabolic syndrome (MetS) components [systolic (SBP) and
      diastolic (DBP) blood pressures, waist circumference, HDL cholesterol,
      triglycerides (TG), and fasting glucose] and gender/race differential risk when
      assessing cardiovascular disease (CVD) risk. METHODS: We estimated a gender- and
      race-specific continuous MetS score using structural equation modeling and tested
      its association with CVD mortality using data from National Health and Nutrition
      Examination Survey III linked with the National Death Index. Cox proportional
      hazard regression tested the association adjusted for sociodemographic and
      behavior characteristics. RESULTS: For men, continuous MetS components associated
      with CVD mortality were SBP (hazard ratio = 1.50, 95% confidence interval = 1.14
      1.96), DBP (1.48, 1.16-1.90), and TG (1.15, 1.12-1.16). In women, SBP (1.44, 1.27
      1.63) and DBP (1.24, 1.02-1.51) were associated with CVD mortality. MetS score
      was not significantly associated with CVD mortality in men; but significant
      associations were found for all women (1.34, 1.06-1.68), non-Hispanic white women
      (1.29, 1.01-1.64), non-Hispanic black women (2.03, 1.12-3.69), and Mexican
      American women (3.57, 2.21-5.76). Goodness-of-fit and concordance were overall
      better for models with the MetS score than MetS (yes/no). CONCLUSIONS: When
      assessing CVD mortality risk, MetS score provided additional information than
      MetS (yes/no).

PMID- 26308483
TI  - Polyomavirus BK and prostate cancer: a complex interaction of potential clinical
      relevance.
AB  - Several studies associating BK polyomavirus (BKPyV) and prostate cancer (PCa)
      suggested that this virus may exert its oncogenic activity at early stages of
      cancer development. The BKPyV oncogene, the large T antigen (LTag), has
      frequently been detected in areas of proliferative inflammatory atrophy, which is
      considered a precursor lesion leading to prostatic intraepithelial neoplasia and
      overt PCa. In a recently updated systematic review, the presence of BKPyV was
      significantly higher in PCa tissues than in healthy control tissues, providing an
      indication for a link between BKPyV infection and cancer risk. In addition,
      recent original investigations highlighted an association between expression of
      the virus and the clinical course of PCa. For example, by studying immune
      responses elicited against BKPyV LTag, a significant association between LTag
      positive cancer lesions and a peculiar regulatory profiling has been observed in
      PCa patients with evidence of disease recurrence after surgical radical
      prostatectomy. Lastly, a study carried out in a larger cohort of patients
      undergoing radical prostatectomy revealed the IgG response against LTag as an
      independent predictor of disease recurrence. Although a full picture of the
      mechanisms potentially responsible for the involvement of BKPyV in PCa is not
      available yet, continuing work on this topic should help to refine the potential
      role of BKPyV in PCa patients, perhaps revealing unsuspected associations with
      the clinical course of this disease.

PMID- 26308482
TI  - In vivo brain rosette spectroscopic imaging (RSI) with LASER excitation, constant
      gradient strength readout, and automated LCModel quantification for all voxels.
AB  - PURPOSE: To optimize the Rosette trajectories for high-sensitivity in vivo brain
      spectroscopic imaging and reduced gradient demands. METHODS: Using LASER
      localization, a rosette based sampling scheme for in vivo brain spectroscopic
      imaging data on a 3 Tesla (T) system is described. The two-dimensional (2D) and
      3D rosette spectroscopic imaging (RSI) data were acquired using 20 * 20 in-plane
      resolution (8 * 8 mm(2) ), and 1 (2D) -18 mm (1.1 cc) or 12 (3D) -8 mm partitions
      (0.5 cc voxels). The performance of the RSI acquisition was compared with a
      conventional spectroscopic imaging (SI) sequence using LASER localization and 2D
      or 3D elliptical phase encoding (ePE). Quantification of the entire RSI data set
      was performed using an LCModel based pipeline. RESULTS: The RSI acquisitions took
      32 s for the 2D scan, and as short as 5 min for the 3D 20 * 20 * 12 scan, using a
      maximum gradient strength Gmax=5.8 mT/m and slew-rate Smax=45 mT/m/ms. The Bland
      Altman agreement between RSI and ePE CSI, characterized by the 95% confidence
      interval for their difference (RSI-ePE), is within 13% of the mean (RSI+ePE)/2.
      Compared with the 3D ePE at the same nominal resolution, the effective RSI voxel
      size was three times smaller while the measured signal-to-noise ratio
      sensitivity, after normalization for differences in effective size, was 43%
      greater. CONCLUSION: 3D LASER-RSI is a fast, high-sensitivity spectroscopic
      imaging sequence, which can acquire medium-to-high resolution SI data in
      clinically acceptable scan times (5-10 min), with reduced stress on the gradient
      system. Magn Reson Med 76:380-390, 2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 26308484
TI  - Differentiating Types of Wide-Complex Tachycardia to Determine Appropriate
      Treatment in the Emergency Department.
AB  - Wide-complex tachycardia is a rare disease entity among patients presenting to
      the emergency department. However, due to its potential life-threatening nature,
      emergency clinicians must know how to assess and manage this condition. Wide
      complex tachycardia encompasses a range of cardiac dysrhythmias, some of which
      can be difficult to distinguish and may require specific treatment approaches.
      This review summarizes the etiology and pathophysiology of wide-complex
      tachycardia, describes the differential diagnosis, and presents an evidence-based
      approach to identification of the different types of tachycardias through the use
      of a thorough history and physical examination, vagal maneuvers,
      electrocardiography, and adenosine. The treatment options and disposition for
      patients with various wide-complex tachycardias are also discussed, with
      attention to special circumstances and select controversial/contemporary topics. 

PMID- 26308485
TI  - Multicenter phase 2 study of patupilone for recurrent or progressive brain
      metastases from non-small cell lung cancer.
AB  - BACKGROUND: Treatment options for patients with non-small cell lung cancer
      (NSCLC) with brain metastases are limited. Patupilone (EPO906), a blood-brain
      barrier-penetrating, microtubule-targeting, cytotoxic agent, has shown clinical
      activity in phase 1/2 studies in patients with NSCLC. This study evaluates the
      efficacy, pharmacokinetics, and safety of patupilone in NSCLC brain metastases.
      METHODS: Adult patients with NSCLC and confirmed progressive brain metastases
      received patupilone intravenously at 10 mg/m(2) every 3 weeks. The primary
      endpoint of this multinomial 2-stage study combined early progression (EP; death
      or progression within 3 weeks) and progression-free survival at 9 weeks (PFS9w)
      to determine drug activity. RESULTS: Fifty patients with a median age of 60 years
      (range, 33-74 years) were enrolled; the majority were men (58%), and most had
      received prior therapy for brain metastases (98%). The PFS9w rate was 36%, and
      the EP rate was 26%. Patupilone blood pharmacokinetic analyses showed mean areas
      under the concentration-time curve from time zero to 504 hours for cycles 1 and 3
      of 1544 and 1978 ng h/mL, respectively, and a mean steady state distribution
      volume of 755 L/m(2) . Grade 3/4 adverse events (AEs), regardless of their
      relation with the study drug, included diarrhea (24%), pulmonary embolisms (8%),
      convulsions (4%), and peripheral neuropathy (4%). All patients discontinued the
      study drug: 31 (62%) for disease progression and 13 (26%) for AEs. Twenty-five of
      32 deaths were due to brain metastases. The median time to progression and the
      overall survival were 3.2 and 8.8 months, respectively. CONCLUSIONS: This is the
      first prospective study of chemotherapy for recurrent brain metastases from
      NSCLC. In this population, patupilone demonstrated activity in heavily treated
      patients.

PMID- 26308487
TI  - Simultaneous chirality and enantiomer separation of metallic single-wall carbon
      nanotubes by gel column chromatography.
AB  - We report the chirality and enantiomer separation of metallic single-wall carbon
      nanotubes (SWCNTs) using gel chromatography, which has been the last remaining
      issue in SWCNT separation that has yet to be achieved. The key to the separation
      is summarized as the following three points: (i) the use of a preseparated
      metallic SWCNT mixture to eliminate the semiconducting SWCNTs that are more
      interactive with the gel; (ii) the reduction of the concentration of dispersant
      to increase the interaction between the metallic SWCNTs and the gel; and (iii)
      the use of a long column to increase the number of interaction sites that enhance
      the slight differences between metallic SWCNT species. Using these three
      separation conditions, we obtained chirality-sorted metallic SWCNTs, especially
      (10,4) metallic SWCNTs were highly enriched. Circular dichroism spectra
      demonstrated the enantiomer separation of metallic SWCNTs. The discrimination of
      the enantiomers is derived from the dextran in the gel, which is the only
      enantiomeric moiety in this system. This is the first report on the enantiomer
      separation of metallic SWCNTs and will contribute to progress in the fundamental
      physics and applications of SWCNTs. 

PMID- 26308488
TI  - Contrast-induced acute kidney injury: the dark side of cardiac catheterization.
AB  - The rapidly growing number of percutaneous coronary interventions has led to a
      considerable improvement in the outcome of patients with acute coronary
      syndromes, yet concurrently exposing patients to enormous volumes of contrast
      media with the inherent risk of renal function impairment. The issue of contrast
      induced acute kidney injury (CI-AKI) is not only associated with direct sequelae
      such as prolonged hospital stay, but also with increased risk of chronic kidney
      disease, recurrent acute coronary syndromes, cerebral ischemia, and increased
      mortality rate. The ubiquitous application of contrast media warrants active
      search for reliable risk factors, diagnostic markers, preventive measures, and
      therapeutic modalities that could be used in the management of CI-AKI. The vast
      majority of CI-AKI incidents remain undiagnosed due to insufficient efficiency of
      the serum creatinine level as the marker of acute kidney injury. Recently,
      several novel renal injury biomarkers have been proposed to facilitate early
      diagnosis of CI-AKI and better reflect the complex interplay between kidney and
      cardiac pathology, known as cardiorenal syndrome. This review aimed to summarize
      the contemporary knowledge on predictors, markers, prevention strategies, and
      management of CI-AKI.

PMID- 26308486
TI  - Notch signaling deregulation in multiple myeloma: A rational molecular target.
AB  - Despite recent therapeutic advances, multiple myeloma (MM) is still an incurable
      neoplasia due to intrinsic or acquired resistance to therapy. Myeloma cell
      localization in the bone marrow milieu allows direct interactions between tumor
      cells and non-tumor bone marrow cells which promote neoplastic cell growth,
      survival, bone disease, acquisition of drug resistance and consequent relapse.
      Twenty percent of MM patients are at high-risk of treatment failure as defined by
      tumor markers or presentation as plasma cell leukemia. Cumulative evidences
      indicate a key role of Notch signaling in multiple myeloma onset and progression.
      Unlike other Notch-related malignancies, where the majority of patients carry
      gain-of-function mutations in Notch pathway members, in MM cell Notch signaling
      is aberrantly activated due to an increased expression of Notch receptors and
      ligands; notably, this also results in the activation of Notch signaling in
      surrounding stromal cells which contributes to myeloma cell proliferation,
      survival and migration, as well as to bone disease and intrinsic and acquired
      pharmacological resistance. Here we review the last findings on the mechanisms
      and the effects of Notch signaling dysregulation in MM and provide a rationale
      for a therapeutic strategy aiming at inhibiting Notch signaling, along with a
      complete overview on the currently available Notch-directed approaches. 

PMID- 26308489
TI  - The Relative Age Effect in German Elite Youth Soccer: Implications for a
      Successful Career.
AB  - PURPOSE: To investigate whether anthropometric profiles and fitness measures vary
      according to birth-date distribution in the German national youth soccer teams
      and to analyze whether there is a difference in the chance of becoming a
      professional soccer player depending on birth quarter (BQ). METHODS: First, 554
      players were divided into 6 age groups (U16-U21), each subdivided into 4 BQs.
      Every player performed at least one 30-m sprint, a countermovement jump, and an
      incremental test to determine individual anaerobic threshold. For players
      performing more than 1 test within a team, the best 1 was included. Since some
      players were part of several different teams, a total of 832 data sets from 495
      individual soccer players, all born from 1987 to 1995, divided into 6 age
      categories (U16-U21) were included. RESULTS: Overall, more players were born in
      BQ1 than in all other BQs (P < .05). No significant difference between BQs could
      be observed in any anthropometric or performance characteristics (P > .18).
      Players born in BQ4 were more likely to become professional than those born in
      BQ1 (odds ratio 3.04, confidence limits 1.53-6.06). CONCLUSION: A relative age
      effect exists in elite German youth soccer, but it is not explained by an
      advantage in anthropometric or performance-related parameters. Younger players
      selected into national teams have a greater chance to become professionals later
      in their career.

PMID- 26308490
TI  - Evidence for a Standardized Preadmission Showering Regimen to Achieve Maximal
      Antiseptic Skin Surface Concentrations of Chlorhexidine Gluconate, 4%, in
      Surgical Patients.
AB  - IMPORTANCE: To reduce the amount of skin surface bacteria for patients undergoing
      elective surgery, selective health care facilities have instituted a preadmission
      antiseptic skin cleansing protocol using chlorhexidine gluconate. A Cochrane
      Collaborative review suggests that existing data do not justify preoperative skin
      cleansing as a strategy to reduce surgical site infection. OBJECTIVES: To develop
      and evaluate the efficacy of a standardized preadmission showering protocol that
      optimizes skin surface concentrations of chlorhexidine gluconate and to compare
      the findings with the design and methods of published studies on preoperative
      skin preparation. DESIGN, SETTING, AND PARTICIPANTS: A randomized prospective
      analysis in 120 healthy volunteers was conducted at an academic tertiary care
      medical center from June 1, 2014, to September, 30, 2014. Data analysis was
      performed from October 13, 2014, to October 27, 2014. A standardized process of
      dose, duration, and timing was used to maximize antiseptic skin surface
      concentrations of chlorhexidine gluconate applied during preoperative showering.
      The volunteers were randomized to 2 chlorhexidine gluconate, 4%, showering groups
      (2 vs 3 showers), containing 60 participants each, and 3 subgroups (no pause, 1
      minute pause, or 2-minute pause before rinsing), containing 20 participants each.
      Volunteers used 118 mL of chlorhexidine gluconate, 4%, for each shower. Skin
      surface concentrations of chlorhexidine gluconate were analyzed using
      colorimetric assay at 5 separate anatomic sites. Individual groups were analyzed
      using paired t test and analysis of variance. INTERVENTION: Preadmission showers
      using chlorhexidine gluconate, 4%. MAIN OUTCOMES AND MEASURES: The primary
      outcome was to develop a standardized approach for administering the preadmission
      shower with chlorhexidine gluconate, 4%, resulting in maximal, persistent skin
      antisepsis by delineating a precise dose (volume) of chlorhexidine gluconate, 4%;
      duration (number of showers); and timing (pause) before rinsing. RESULTS: The
      mean (SD) composite chlorhexidine gluconate concentrations were significantly
      higher (P < .001) in the 1- and 2-minute pause groups compared with the no-pause
      group in participants taking 2 (978.8 [234.6], 1042.2 [219.9], and 265.6 [113.3]
      ug/mL, respectively) or 3 (1067.2 [205.6], 1017.9 [227.8], and 387.1 [217.5]
      ug/mL, respectively) showers. There was no significant difference in
      concentrations between 2 and 3 showers or between the 1- and 2-minute pauses.
      CONCLUSIONS AND RELEVANCE: A standardized preadmission shower regimen that
      includes 118 mL of aqueous chlorhexidine gluconate, 4%, per shower; a minimum of
      2 sequential showers; and a 1-minute pause before rinsing results in maximal skin
      surface (16.5 ug/cm2) concentrations of chlorhexidine gluconate that are
      sufficient to inhibit or kill gram-positive or gram-negative surgical wound
      pathogens. This showering regimen corrects deficiencies present in current
      nonstandardized preadmission shower protocols for patients undergoing elective
      surgery.

PMID- 26308491
TI  - Lysozyme-Based Antibacterial Nanomotors.
AB  - An effective and rapid bacterial killing nanotechnology strategy based on
      lysozyme-modified fuel-free nanomotors is demonstrated. The efficient
      antibacterial property of lysozyme, associated with the cleavage of glycosidic
      bonds of peptidoglycans present in the bacteria cell wall, has been combined with
      ultrasound (US)-propelled porous gold nanowire (p-AuNW) motors as biocompatible
      dynamic bacteria nanofighters. Coupling the antibacterial activity of the enzyme
      with the rapid movement of these p-AuNWs, along with the corresponding fluid
      dynamics, promotes enzyme-bacteria interactions and prevents surface aggregation
      of dead bacteria, resulting in a greatly enhanced bacteria-killing capability.
      The large active surface area of these nanoporous motors offers a significantly
      higher enzyme loading capacity compared to nonporous AuNWs, which results in a
      higher antimicrobial activity against Gram-positive and Gram-negative bacteria.
      Detailed characterization studies and control experiments provide useful insights
      into the underlying factors controlling the antibacterial performance of the new
      dynamic bacteria nanofighters. Rapid and effective killing of the Gram-positive
      Micrococcus lysodeikticus bacteria (69-84% within 1-5 min) is demonstrated. 

PMID- 26308492
TI  - Stress and emotional valence effects on children's versus adolescents' true and
      false memory.
AB  - Despite considerable interest in understanding how stress influences memory
      accuracy and errors, particularly in children, methodological limitations have
      made it difficult to examine the effects of stress independent of the effects of
      the emotional valence of to-be-remembered information in developmental
      populations. In this study, we manipulated stress levels in 7-8- and 12-14-year
      olds and then exposed them to negative, neutral, and positive word lists. Shortly
      afterward, we tested their recognition memory for the words and false memory for
      non-presented but related words. Adolescents in the high-stress condition were
      more accurate than those in the low-stress condition, while children's accuracy
      did not differ across stress conditions. Also, among adolescents, accuracy and
      errors were higher for the negative than positive words, while in children, word
      valence was unrelated to accuracy. Finally, increases in children's and
      adolescents' cortisol responses, especially in the high-stress condition, were
      related to greater accuracy but not false memories and only for positive
      emotional words. Findings suggest that stress at encoding, as well as the
      emotional content of to-be-remembered information, may influence memory in
      different ways across development, highlighting the need for greater complexity
      in existing models of true and false memory formation. 

PMID- 26308493
TI  - Identification and Characterization of Androgen-Responsive Genes in Zebrafish
      Embryos.
AB  - Responsive genes for fish embryos have been identified so far for some endocrine
      pathways but not for androgens. Using transcriptome analysis and multiple
      concentration-response modeling, we identified putative androgen-responsive genes
      in zebrafish embryos exposed to 0.05-5000 nM 11-ketotestosterone for 24 h. Four
      selected genes with sigmoidal concentration-dependent expression profiles (EC50 =
      6.5-30.0 nM) were characterized in detail. The expression of cyp2k22 and slco1f4
      was demonstrated in the pronephros; lipca was detected in the liver, and sult2st3
      was found in the olfactory organs and choroid plexus. Their expression domains,
      the function of human orthologs, and a pathway analysis suggested a role of these
      genes in the metabolism of hormones. Hence, it was hypothesized that they were
      induced to compensate for elevated hormone levels. The induction of sult2st3 and
      cyp2k22 by 11-ketotestosterone was repressed by co-exposure to the androgen
      receptor antagonist nilutamide supporting a potential androgen receptor mediated
      regulation. Sensitivity (expressed as EC50 values) of sult2st3 and cyp2k22 gene
      expression induction after exposure to other steroidal hormones (11
      ketotestosterone ~ testosterone > progesterone > cortisol > ethinylestradiol)
      correlated with their known binding affinities to zebrafish androgen receptor.
      Hence, these genes might represent potential markers for screening of androgenic
      compounds in the zebrafish embryo.

PMID- 26308494
TI  - List intonation in pre-schoolers with normal and disordered language development.
AB  - The principal aim of this study was to evaluate pre-schoolers' expressive
      intonation in light of current debates about the underlying nature of language
      impairment (LI). Children with LI typically have deficits in grammar, a component
      of language that is phonologically represented on the segmental level. The
      hypothesis is that children with LI do not have deficits of this type when
      grammar is conveyed by intonation, a pitch-based component of language that is
      phonologically represented on the suprasegmental level. This study focused on the
      richly diversified suprasegmental patterns of sentences in which the speaker
      produces a series of items in a list. To address the hypothesis, list intonation
      in the speech of 4-year-olds with and without LI was acoustically analysed. Lists
      produced by children with LI were comparable to those produced by children with
      normal language development (NL). The results do not support the claim that LI
      stems from a poor understanding of grammatical principles. Rather, LI reflects an
      underlying impairment of segmental information processing. The discussion focuses
      on two characteristics of pitch contours which may account for the resilience of
      intonation in children with LI. Namely, steady state versus transient signals and
      universal symbol meanings versus arbitrary relationships between form and
      function. 

PMID- 26308495
TI  - Dielectric Mismatch Mediates Carrier Mobility in Organic-Intercalated Layered
      TiS2.
AB  - The dielectric constant is a key parameter that determines both optical and
      electronic properties of materials. It is desirable to tune electronic properties
      though dielectric engineering approach. Here, we present a systematic approach to
      tune carrier mobilities of hybrid inorganic/organic materials where layered two
      dimensional transition-metal dichalcogenide TiS2 is electrochemically
      intercalated with polar organic molecules. By manipulating the dielectric
      mismatch using polar organic molecules with different dielectric constants,
      ranging from 10 to 41, the electron mobility of the TiS2 layers was changed three
      times due to the dielectric screening of the Coulomb-impurity scattering
      processes. Both the overall thermal conductivity and the lattice thermal
      conductivity were also found to decrease with an increasing dielectric mismatch.
      The enhanced electrical mobility along with the decreased thermal conductivity
      together gave rise to a significantly improved thermoelectric figure of merit of
      the hybrid inorganic/organic materials at room temperature, which might find
      applications in wearable electronics. 

PMID- 26308496
TI  - Novel skeleton sesquiterpenoids isolated from guava leaves.
AB  - A chemical investigation of the plant Psidium guajava L., collected in Guangdong
      province, afforded two novel skeleton sesquiterpenoids 1 and 2. Compound 2 also
      known as isocaryolan-9-one was a new natural product. The structure of the novel
      compound 1 was determined as guavacid A by various spectroscopic methods. A
      possible biosynthetic pathway for 1 and 2 was proposed. 

PMID- 26308497
TI  - Student-Retention and Career-Placement Rates Between Bachelor's and Master's
      Degree Professional Athletic Training Programs.
AB  - CONTEXT: The debate over what the entry-level degree should be for athletic
      training has heightened. A comparison of retention and career-placement rates
      between bachelor's and master's degree professional athletic training programs
      may inform the debate. OBJECTIVE: To compare the retention rates and career
      placement rates of students in bachelor's and master's degree professional
      programs. DESIGN: Cross-sectional study. SETTING: Web-based survey. PATIENTS OR
      OTHER PARTICIPANTS: A total of 192 program directors (PDs) from bachelor's degree
      (n = 177) and master's degree (n = 15) professional programs. INTERVENTION(S):
      The PDs completed a Web-based survey. MAIN OUTCOME MEASURE(S): We instructed the
      PDs to provide a retention rate and career-placement rate for the students in the
      programs they lead for each of the past 5 years. We also asked the PDs if they
      thought retention of students was a problem currently facing athletic training
      education. We used independent t tests to compare the responses between
      bachelor's and master's degree professional programs. RESULTS: We found a higher
      retention rate for professional master's degree students (88.70% +/- 9.02%, 95%
      confidence interval [CI] = 83.71, 93.69) than bachelor's degree students (80.98%
      +/- 17.86%, 95% CI = 78.30, 83.66) (t25 = -2.86, P = .008, d = 0.55). Similarly,
      PDs from professional master's degree programs reported higher career-placement
      percentages (88.50% +/- 10.68%, 95% CI = 82.33, 94.67) than bachelor's degree
      professional PDs (71.32% +/- 18.47%, 95% CI = 68.54, 74.10) (t20 = -5.40, P <
      .001, d = 1.14). Finally, we observed no difference between groups regarding
      whether retention is a problem facing athletic training (chi(2)1 = 0.720, P =
      .40, Phi = .061). CONCLUSIONS: Professional master's degree education appears to
      facilitate higher retention rates and greater career-placement rates in athletic
      training than bachelor's degree education. Professional socialization, program
      selectivity, and student commitment and motivation levels may help to explain the
      differences noted.

PMID- 26308498
TI  - Improving Single-Legged-Squat Performance: Comparing 2 Training Methods With
      Potential Implications for Injury Prevention.
AB  - CONTEXT: Poor dynamic limb alignment during loading tasks has links to the
      development of knee injuries, including patellofemoral pain and anterior cruciate
      ligament injury. Therefore, modalities to improve limb alignment during loading
      tasks are thought to reduce loading through these structures and potentially
      prevent injury. OBJECTIVE: To compare hip-strengthening and skill-acquisition
      training to examine if they can improve lower limb biomechanics, potentially
      preventing injury, and to examine whether changes demonstrated can be maintained
      after 6 weeks of no practice. DESIGN: Controlled laboratory study. SETTING:
      Laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 19 recreationally active
      individuals volunteered, and 17 (9 women: age = 27.9 +/- 3.1 years, height =
      165.4 +/- 8.4 cm, mass = 60.5 +/- 9.2 kg; 8 men: age = 30.4 +/- 6.4 years, height
      = 181.4 +/- 7.1 cm, mass = 69.8 +/- 15.2 kg) completed the study. Nine
      participants were allocated to a hip-strengthening program; 8, to a skill
      acquisition program. INTERVENTION(S): Participants performed a 6-week training
      program of either hip strengthening (n = 9) or skill acquisition (n = 8) 3 times
      per week. MAIN OUTCOME MEASURE(S): Measurements of clam-exercise strength, hip
      abduction strength, frontal-plane projection angle, hip-adduction angle, and a
      qualitative score were taken at baseline, 6 weeks, and 12 weeks. RESULTS: We
      observed improvements in frontal-plane projection angle (strength: t8 = 5.344, P
      = .001; skill: t7 = 4.393, P = .003), hip-adduction angle (strength: t8 = 3.597,
      P = .007; skill: t7 = 4.722, P = .002), and qualitative score (strength: t8 =
      3.900, P = .005; skill: t7 = 8.283, P < .001) postintervention, which were
      retained at the 12-week retest in both groups. CONCLUSIONS: A 6-week intervention
      of either hip-strengthening or skill-acquisition training improved lower limb
      biomechanics. The changes in biomechanics after skill training were retained at
      12 weeks, suggesting a change in motor patterning that could be favorable to
      longer-term injury prevention.

PMID- 26308500
TI  - Complex Internal Bias Fields in Ferroelectric Hafnium Oxide.
AB  - For the rather new hafnia- and zirconia-based ferroelectrics, a lot of questions
      are still unsettled. Among them is the electric field cycling behavior consisting
      of (1) wake-up, (2) fatigue, and (3) the recently discovered subcycling-induced
      split-up/merging effect of transient current peaks in a hysteresis measurement.
      In the present work, first-order reversal curves (FORCs) are applied to study the
      evolution of the switching and backswitching field distribution within the frame
      of the Preisach model for three different phenomena: (1) The pristine film
      contains two oppositely biased regions. These internal bias fields vanish during
      the wake-up cycling. (2) Fatigue as a decrease in the number of switchable
      domains is accompanied by a slight increase in the mean absolute value of the
      switching field. (3) The split-up effect is shown to also be related to local
      bias fields in a complex situation resulting from both the field cycling
      treatment and the measurement procedure. Moreover, the role of the wake-up
      phenomenon is discussed with respect to optimizing low-voltage operation
      conditions of ferroelectric memories toward reasonably high and stable remanent
      polarization and highest possible endurance. 

PMID- 26308501
TI  - The progress of immunotherapy for glioblastoma.
AB  - Glioblastoma is the most common primary brain tumor in adults, accounting for
      about half of all primary brain tumors. Despite multiple therapeutic
      interventions such as surgical resection, radiotherapy, and systemic
      chemotherapy, the prognosis for glioblastoma remains poor. Due to the scientific
      community's enhanced understanding of the CNS immune system and significant
      achievements in tumor immunotherapy in recent years, immunotherapy has become a
      promising GBM treatment. In vaccine therapy, a number of clinical trials have
      achieved encouraging results. In antibody therapy, antibodies are used to target
      immune checkpoints such as ipilimumab and nivolumab. Bioengineering technology
      has also lead to a new field of tumor immunotherapy, whereby genetically modified
      tumor-specific T cells are reintroduced into a patient's body. 

PMID- 26308502
TI  - The Role of FDG-PET in the Diagnosis and Staging of Ocular Adnexal
      Lymphoproliferative Disease.
AB  - PURPOSE: To further evaluate fluorine 18 fluoro-deoxyglucose positron emission
      tomography (FDG PET) in the staging of ocular adnexal lymphoproliferative disease
      (OALD). METHODS: Retrospective and prospective case series with review of
      clinical and imaging records including computed tomography (CT), FDG PET (+/-
      PET/CT) and/or magnetic resonance imaging (MRI). RESULTS: Thirty-four patients
      had FDG PET and CT scans at initial staging. Eleven were retrospectively reviewed
      and 23 were prospectively enrolled. Of 34 patients, 17 (50%) had primary disease,
      17 (50%) had secondary and of these, 13 patients (38%) had OALD as their initial
      manifestation. Sixteen patients had active systemic disease in conjunction with
      their orbital disease. Systemic disease was demonstrated by FDG PET (+/- CT) in
      15 of 16 (94%) patients and 11 of 16 (69%) patients with CT. FDG PET found
      orbital disease in 27 of 34 patients (79%) versus 33 of 34 patients with orbital
      CT (97%). Four of 16 patients in which FDG-PET detected systemic disease where CT
      did not were upstaged and their management changed significantly in 5 cases.
      CONCLUSIONS: This study reaffirms FDG PET as an important part of initial
      staging. Our study suggests FDG PET detects systemic disease more reliably than
      CT alone and results in significant changes in management. Our findings suggest
      FDG PET detection for local OALD is less sensitive than CT. MRI is helpful in
      augmenting other imaging modalities in further identifying disease. Given the
      prevalence of simultaneous systemic presentations of OALD, FDG PET in this regard
      is especially important and highlights the need for coordinated multidisciplinary
      care.

PMID- 26308503
TI  - The Role of Virus Infection in Deregulating the Cytokine Response to Secondary
      Bacterial Infection.
AB  - Proinflammatory cytokines are produced by macrophages and dendritic cells (DCs)
      after infection to stimulate T helper (Th) cells, linking innate and adaptive
      immunity. Virus infections can deregulate the proinflammatory cytokine response
      like tumor necrosis factor-alpha and interleukin (IL)-2, making the host more
      susceptible to secondary bacterial infections. Studies using various viruses such
      as lymphocytic choriomeningitis virus, influenza A virus, and human
      immunodeficiency virus have revealed several intriguing mechanisms that account
      for the increased susceptibility to several prevalent bacterial infections. In
      particular, type I interferons induced during a virus infection have been
      observed to play a role in suppressing the production of some key antibacterial
      proinflammatory cytokines such as IL-23 and IL-17. Other suppressive mechanisms
      as a result of cytokine deregulation by viral infections include reduced function
      of immune cells such as DC, macrophage, natural killer, CD4(+), and CD8(+) T
      cells leading to impaired clearance of secondary bacterial infections. In this
      study, we highlight some of the immune mechanisms that become deregulated by
      viral infections, and can thus become defective during secondary bacterial
      infections. 

PMID- 26308504
TI  - Heparins in ulcerative colitis: proposed mechanisms of action and potential
      reasons for inconsistent clinical outcomes.
AB  - Current drug therapies for ulcerative colitis (UC) are not completely effective
      in managing moderate-to-severe UC and approximately 20% of patients with severe
      UC require surgical interventions. Heparins, polydisperse mixtures of non
      anticoagulant and anticoagulant oligosaccharides, are widely used as
      anticoagulants. However, heparins are also reported to have anti-inflammatory
      properties. Unfractionated heparin was initially used in patients with UC for the
      treatment of rectal microthrombi. Surprisingly, it was found to be effective in
      reducing UC-associated symptoms. Since then, several pre-clinical and clinical
      studies have reported promising outcomes of heparins in UC. In contrast, some
      controlled clinical trials demonstrated no or only limited benefits, thus the
      potential of heparins for the treatment of UC remains uncertain. This review
      discusses potential mechanisms of action of heparins, as well as proposed reasons
      for their contradictory clinical effectiveness in the treatment of UC. 

PMID- 26308505
TI  - Toward Clinical Application of the Bioartificial Pancreas.

PMID- 26308506
TI  - Diabetes Is Reversed in a Murine Model by Marginal Mass Syngeneic Islet
      Transplantation Using a Subcutaneous Cell Pouch Device.
AB  - BACKGROUND: Islet transplantation is a successful beta-cell replacement therapy
      for selected patients with type 1 diabetes mellitus. Although high rates of early
      insulin independence are achieved routinely, long-term function wanes over time.
      Intraportal transplantation is associated with procedural risks, requires
      multiple donors, and does not afford routine biopsy. Stem cell technologies may
      require potential for retrievability, and graft removal by hepatectomy is
      impractical. There is a clear clinical need for an alternative, optimized
      transplantation site. The subcutaneous space is a potential substitute, but
      transplantation of islets into this site has routinely failed to reverse
      diabetes. However, an implanted device, which becomes prevascularized before
      transplantation, may alter this equation. METHODS: Syngeneic mouse islets were
      transplanted subcutaneously within Sernova Corp's Cell Pouch (CP). All recipients
      were preimplanted with CPs 4 weeks before diabetes induction and transplantation.
      After transplantation, recipients were monitored for glycemic control and glucose
      tolerance. RESULTS: Mouse islets transplanted into the CP routinely restored
      glycemic control with modest delay and responded well to glucose challenge,
      comparable to renal subcapsular islet grafts, despite a marginal islet dose, and
      normoglycemia was maintained until graft explantation. In contrast, islets
      transplanted subcutaneously alone failed to engraft. Islets within CPs stained
      positively for insulin, glucagon, and microvessels. CONCLUSIONS: The CP is
      biocompatible, forms an environment suitable for islet engraftment, and offers a
      potential alternative to the intraportal site for islet and future stem cell
      therapies.

PMID- 26308507
TI  - Substance abuse relapse in Oxford House recovery homes: A survival analysis
      evaluation.
AB  - BACKGROUND: This study used survival analysis to examine risk factors for
      substance abuse relapse among residents in Oxford Houses (OH), a national network
      of self-run, self-financed aftercare homes for individuals recovering from
      substance use disorders. METHODS: Participants who entered OH within 60 days of a
      1-year longitudinal study (N = 268) were selected from of a nationally
      representative US sample. Discrete-time survival analysis compared baseline risk
      of relapse with 4 hypothesized survival models that included time-invariant and
      time-varying factors across 3 subsequent time periods. RESULTS: The model
      predicting higher risk for more severe substance use disorders and psychiatric
      problems was supported. The hypothesized model that predicted time-varying
      increases in alcohol (but not drug) abstinence self-efficacy significantly
      affected risk of relapse. Hypothesized demographic and employment variables did
      not significantly predict relapse risk. CONCLUSIONS: Results suggested that OH
      recovery homes may reduce relapse by providing closer monitoring and referring
      additional services to new residents with more severe prior addiction severity.
      Risk for relapse may also be reduced by enhancing abstinence self-efficacy for
      alcohol regardless of drug of choice.

PMID- 26308508
TI  - Mechanism for Collective Cell Alignment in Myxococcus xanthus Bacteria.
AB  - Myxococcus xanthus cells self-organize into aligned groups, clusters, at various
      stages of their lifecycle. Formation of these clusters is crucial for the complex
      dynamic multi-cellular behavior of these bacteria. However, the mechanism
      underlying the cell alignment and clustering is not fully understood. Motivated
      by studies of clustering in self-propelled rods, we hypothesized that M. xanthus
      cells can align and form clusters through pure mechanical interactions among
      cells and between cells and substrate. We test this hypothesis using an agent
      based simulation framework in which each agent is based on the biophysical model
      of an individual M. xanthus cell. We show that model agents, under realistic cell
      flexibility values, can align and form cell clusters but only when periodic
      reversals of cell directions are suppressed. However, by extending our model to
      introduce the observed ability of cells to deposit and follow slime trails, we
      show that effective trail-following leads to clusters in reversing cells.
      Furthermore, we conclude that mechanical cell alignment combined with slime-trail
      following is sufficient to explain the distinct clustering behaviors observed for
      wild-type and non-reversing M. xanthus mutants in recent experiments. Our results
      are robust to variation in model parameters, match the experimentally observed
      trends and can be applied to understand surface motility patterns of other
      bacterial species. 

PMID- 26308509
TI  - Cerebral protection during neurosurgery and stroke.
AB  - PURPOSE OF REVIEW: This article reviews the recent evidence on perioperative
      neuroprotection in patients undergoing brain surgery and in patients with acute
      stroke. RECENT FINDINGS: With varying degrees of success, numerous
      pharmacological and nonpharmacological therapies have been employed to provide
      neuroprotection for patients during the perioperative period and after acute
      ischemic stroke (IAS). Recent studies have failed to demonstrate neuroprotective
      effects of intraoperative remifentanil or propofol use, although hypertonic
      saline may provide better brain relaxation than mannitol during elective
      intracranial surgery for tumor. Magnesium sulfate offers no improvement in
      neurological outcome at 90 days after stroke. Medical management alone may be
      superior to medical management with interventional therapy for the prevention of
      death or stroke in unruptured arteriovenous malformations. In patients with IAS
      with a proximal vessel occlusion, small infarct core, and moderate-to-good
      collateral circulation, rapid endovascular treatment resulted in improved
      functional outcomes and reduced mortality. For endovascular clot evacuation after
      IAS, conscious sedation may be safer than general anaesthesia. SUMMARY: Recent
      evidence provides insufficient evidence of neuroprotective strategies to guide
      clinical management, and more randomized clinical trials are needed to optimize
      patient care.

PMID- 26308510
TI  - Preparing for budget-based payment methodologies: global payment and episode
      based payment.
AB  - PURPOSE OF REVIEW: Use of budget-based payment methodologies (capitation and
      episode-based bundled payment) has been demonstrated to drive value in healthcare
      delivery. With a focus on high-volume, high-cost surgical procedures, inclusion
      of anaesthesiology services in these methodologies is likely. This review
      provides a summary of budget-based payment methodologies and practical
      information necessary for anaesthesiologists to prepare for participation in
      these programmes. RECENT FINDINGS: Although few examples of anaesthesiologists'
      participation in these models exist, an understanding of the structure of these
      programmes and opportunities for participation are available. Prospective
      preparation in developing anaesthesiology-specific bundled payment profiles and
      early participation in pathway development associated with selected episodes of
      care are essential for successful participation as a gainsharing partner.
      SUMMARY: With significant opportunity to contribute to care coordination and cost
      management, anaesthesiology can play an important role in budget-based payment
      programmes and should expect to participate as full gainsharing partners. Precise
      costing methodologies and accurate economic modelling, along with identification
      of quality management and cost control opportunities, will help identify
      participation opportunities and appropriate payment and gainsharing agreements.
      Anaesthesiology-specific examples with budget-based payment models are needed to
      help guide increased participation in these programmes.

PMID- 26308511
TI  - Update on paravertebral blocks.
AB  - PURPOSE OF REVIEW: The goal of this review was to update the reader on the
      developments and advancements that have transpired in the previous few years and
      to encourage an open dialogue amongst readers and researchers alike. RECENT
      FINDINGS: Tremendous progress has been made investigating the part paravertebral
      blocks play, not only in acute pain management but also in management of
      nonsurgical pain. It starts with discussing the recent advances pertaining to
      paravertebral blocks (PVBs) in breast, thoracic and cardiac surgery and then
      leads on to its evolving presence in pediatric surgery. The review also discusses
      utilization of thoracic paravertebral blocks in managing acute and chronic
      nonsurgical pain. Finally, it concludes with mention of new techniques and
      procedures to perform PVBs. SUMMARY: The impact of paravertebral analgesia on
      cancer pain and prevention of metastasis could be huge once enough data have
      accumulated. The steady influx of data on PVBs has led to the resurgence of this
      block in almost every area of acute pain management.

PMID- 26308512
TI  - Three-dimensional ultrasound imaging.
AB  - PURPOSE OF REVIEW: Ultrasound guidance is frequently utilized for needle
      placement and observation of local anesthetic spread when performing peripheral
      nerve blocks. Although there is evidence that ultrasound technology can reduce
      complications, there are limitations to 2-dimensional (2-D) ultrasound. Three
      dimensional (3-D) and especially real-time 3-D (4-D) ultrasound may allow for
      optimized and well tolerated needle positioning and enhanced observation of local
      anesthetic spread around the target structure. This article reviewed the current
      literature regarding the use of 3-D and 4-D ultrasound technology in a regional
      anesthesia setting. RECENT FINDINGS: Several investigations have utilized 3-D
      ultrasound as a tool to study anatomical spatial relationships, evaluate local
      anesthetic spread, or optimize nerve block needle or catheter positioning.
      However, this was mostly achieved by retrospectively generating a 3-D image after
      the performance of the actual nerve blocks or studying anatomy on volunteers.
      There are only a few case reports available demonstrating the feasibility of 4-D
      ultrasound for nerve block performance. SUMMARY: At present, there are limited
      data regarding the use of 3-D ultrasound and a complete lack of randomized
      controlled clinical trials evaluating the potential benefits of real-time 3-D (4
      D) ultrasound. This may be in part due to technical limitations associated with
      these techniques.

PMID- 26308513
TI  - Liposomal bupivacaine for regional anesthesia.
AB  - PURPOSE OF REVIEW: Using a regional block in a multimodal approach to
      postoperative analgesia management involves addressing, which local anesthetic
      and how much should be used to ensure adequate pain relief to reduce related
      morbidity and mortality. This article will review literature surrounding the
      recently approved formulation of slow release liposomal bupivacaine, define its
      proven benefits, and identify ongoing studies to further examine the utility of
      this novel formulation by various routes. RECENT FINDINGS: Recent Phase II and
      III clinical trials have demonstrated the ability of liposomal bupivacaine to
      provide prolonged analgesia, maintain a high safety profile in therapeutic doses,
      and decrease opioid requirements when compared with placebo in local infiltration
      applications for up to 24 h. Between 24 and 72 h after study drug administration,
      there was minimal to no difference between EXPAREL and placebo treatments on mean
      pain intensity. Conventional bupivacaine or ropivacaine groups (current standard
      practice in many hospitals in the USA) were not compared. In addition, the
      analgesic efficacy, cost-effectiveness, and safety profile of liposomal
      bupivacaine has not thoroughly been studied in various standard clinical settings
      such as perineural, intrathecal, and epidural administration. SUMMARY: Current
      published data do not provide superior clinical results for EXPAREL over
      conventional bupivacaine based upon the lack of adequately powered multicentered
      clinical trials with comparison groups. Further investigation is necessary to
      identify the analgesic efficacy and safety profile of liposomal bupivacaine
      versus standard local anesthetics and to define the optimal clinical indication
      for liposomal bupivacaine administration in regional anesthesia.

PMID- 26308514
TI  - Anaesthesia for deep brain stimulation: a review.
AB  - PURPOSE OF REVIEW: Deep brain stimulation (DBS) is a well tolerated and
      efficacious surgical treatment for movement disorders, chronic pain, psychiatric
      disorder, and a growing number of neurological disorders. Given that the brain
      targets are deep and small, accurate electrode placement is commonly accomplished
      by utilizing frame-based systems. DBS electrode placement is confirmed by
      microlectrode recordings and macrostimulation to optimize and verify target
      placement. With a reliance on electrophysiology, proper anaesthetic management is
      paramount to balance patient comfort without interfering with neurophysiology.
      RECENT FINDINGS: To achieve optimal pain control, generous amounts of local
      anaesthesia are instilled into the planned incision. During the opening and
      closing states, conscious sedation is the prevailing method of anaesthesia. The
      preferred agents are dexmedetomidine, propofol, and remifentanil, as they affect
      neurocognitive testing the least, and shorter acting. All the agents are turned
      off 15-30 min prior to microelectrode recording. Dexmedetomidine has gained
      popularity in DBS procedures, but has some considerations at higher doses. The
      addition of ketamine is helpful for pediatric cases. SUMMARY: DBS is a robust
      surgical treatment for a variety of neurological disorders. Appropriate
      anaesthetic agents that achieve patient comfort without interfering with
      electrophysiology are paramount.

PMID- 26308515
TI  - Paediatric regional anaesthesia: a current perspective.
AB  - PURPOSE OF REVIEW: Effective analgesia is necessary for optimal recovery after
      surgery, but children often do not attain adequate postoperative pain control.
      This review examines the current trends in paediatric regional anaesthesia.
      RECENT FINDINGS: Better pain assessment and therapeutic regimens are needed for
      our patients. Trunk blocks such as paravertebral, transversus abdominis plane,
      rectus sheath and ilioinguinal/iliohypogastric are becoming a popular means of
      providing analgesia for thoracic and abdominal procedures. The introduction of
      ultrasound guidance improves accuracy, efficacy, and safety of regional
      anaesthesia, and also decreases the amount of local anaesthetic injected. Single
      injection nerve blocks have a limited duration and the patients can benefit from
      adding an adjunct to local anaesthetic or placing a catheter. The use of adjuncts
      is reasonable, but it is difficult to find a medication with both minimal side
      effects and the ability to combat pain for extended periods of time. More
      peripheral nerve block catheters are used in the paediatric inpatient and
      outpatient settings and recent data support the feasibility and efficacy of
      ambulatory peripheral nerve catheters. SUMMARY: By using a multimodal approach
      that includes regional anaesthesia, paediatric pain management should aim to
      reduce patients' pain to an acceptable level without compromising their degree of
      mobilization. Undoubtedly, peripheral nerve blocks improve analgesia, but future
      large prospective studies should be conducted to further delineate their
      effectiveness, duration and safety.

PMID- 26308516
TI  - Gender aspects in postoperative pain.
AB  - PURPOSE OF REVIEW: Gender differences are well known in clinical pain and pain
      related diseases. However, studies analyzing gender differences in postoperative
      pain yielded inconsistent finding. The aim of this review was to summarize recent
      findings on this matter. RECENT FINDINGS: We found 58 recently published studies
      (September 2013-March 2015) assessing gender differences on patients undergoing
      various surgical procedures. Studies focusing on one type or one category of
      surgical procedures suggest that women report higher postoperative pain scores
      after thoracic, cardiac and neurosurgical procedures. However, gender differences
      after abdominal and orthopedic surgeries were inconsistent and after oral surgery
      inexistent. Studies including various surgical procedures indicate a more
      consistent gender difference, presumably because of the greater number of
      patients included. However, the net difference in almost every study was small.
      SUMMARY: Women seem to be at higher risk to develop severe postoperative pain but
      gender differences seem to be small and of low clinical relevance. We argue that
      major confounders may explain discrepancies between studies. Large prospective
      studies and registry data assessing gender aspects including confounders need to
      be done in the future.

PMID- 26308517
TI  - Pediatric neuroanesthesia.
AB  - PURPOSE OF REVIEW: A series of recent studies have changed the practice of
      pediatric neuroanesthesia, improving outcomes and making children's quality of
      life better. RECENT FINDINGS: Potential long-term neurologic effects in infants
      and young children undergoing surgery and anesthesia have been recognized for
      over a decade. Several recent, well performed studies suggest that hypotension
      may also be a major contributor to postoperative neurologic impairment in
      children. Craniosynostosis surgery has also been the subject of extensive study,
      both related to decreasing blood loss and to optimizing postoperative outcomes.
      SUMMARY: Although neurosurgical anesthesia research in the pediatric population
      can be ethically and logistically complex, resolving questions such as the
      optimal blood pressure during surgery and best management of infants undergoing
      repair of craniosynostosis will improve patient outcomes.

PMID- 26308518
TI  - Anaesthesia for the paediatric outpatient.
AB  - PURPOSE OF REVIEW: The aim of this review was to discuss recent developments in
      paediatric anaesthesia, which are particularly relevant to the practitioner
      involved in paediatric outpatient anaesthesia. RECENT FINDINGS: The use of a
      pharmacological premedication is still a matter of debate. Several publications
      are focussing on nasal dexmedetomidine; however, its exact place has not yet been
      defined. Both inhalational and intravenous anaesthesia techniques still have
      their advocates; for diagnostic imaging, however, propofol is emerging as the
      agent of choice. The disappearance of codeine has left a breach for an oral
      opioid and has probably worsened postoperative analgesia following tonsillectomy.
      In recent years, a large body of evidence for the prevention of postoperative
      agitation has appeared. Alpha-2-agonists as well as the transition to propofol
      play an important role. There is now some consensus that for reasons of
      practicability prophylactic antiemetics should be administered to all and not
      only to selected high-risk patients. SUMMARY: Perfect organization of the whole
      process is a prerequisite for successful paediatric outpatient anaesthesia. In
      addition, the skilled practitioner is able to provide a smooth anaesthetic,
      minimizing complications, and, finally, he has a clear concept for avoiding
      postoperative pain, agitation and vomiting.

PMID- 26308519
TI  - Ambulatory anaesthesia and cognitive dysfunction.
AB  - PURPOSE OF REVIEW: More surgical procedures are performed on an ambulatory basis
      and the advantages are apparent, but outpatient surgery presents challenges
      because of the expectation of a fast recovery soon after termination of
      anaesthesia. Ambulatory surgery is a well tolerated regimen with few serious
      adverse outcomes, hence difficult to obtain sound scientific evidence for
      avoiding complications. RECENT FINDINGS: Few studies have assessed recovery of
      cognitive function after ambulatory surgery, but it seems that both propofol and
      modern volatile anaesthetics are rational choices for general anaesthesia in the
      outpatient setting. Cognitive complications such as delirium and postoperative
      cognitive dysfunction are less frequent in ambulatory surgery than with
      hospitalization. SUMMARY: The elderly are especially susceptible to adverse
      effects of the hospital environment such as immobilisation, sleep deprivation,
      unfamiliar surroundings, and medication errors. Enhanced recovery programmes
      (fast-track regimens) may allow earlier discharge which is probably beneficial
      for the elderly. Frailty is becoming an increasingly important concept that needs
      to be clinically considered in elderly patients, as well as in future studies.

PMID- 26308520
TI  - HMPL: A Pipeline for Identifying Hemimethylation Patterns by Comparing Two
      Samples.
AB  - DNA methylation (the addition of a methyl group to a cytosine) is an important
      epigenetic event in mammalian cells because it plays a key role in regulating
      gene expression. Most previous methylation studies assume that DNA methylation
      occurs on both positive and negative strands. However, a few studies have
      reported that in some genes, methylation occurs only on one strand (ie,
      hemimethylation) and has clustering patterns. These studies report that
      hemimethylation occurs on individual genes. It is unclear whether hemimethylation
      occurs genome-wide and whether there are hemimethylation differences between
      cancerous and noncancerous cells. To address these questions, we have developed
      the first-ever pipeline, named hemimethylation pipeline (HMPL), to identify
      hemimethylation patterns. Utilizing the available software and the newly
      developed Perl and R scripts, HMPL can identify hemimethylation patterns for a
      single sample and can also compare two different samples. 

PMID- 26308521
TI  - Patterns and Variation in Benthic Biodiversity in a Large Marine Ecosystem.
AB  - While there is a persistent inverse relationship between latitude and species
      diversity across many taxa and ecosystems, deviations from this norm offer an
      opportunity to understand the conditions that contribute to large-scale diversity
      patterns. Marine systems, in particular, provide such an opportunity, as marine
      diversity does not always follow a strict latitudinal gradient, perhaps because
      several hypothesized drivers of the latitudinal diversity gradient are
      uncorrelated in marine systems. We used a large scale public monitoring dataset
      collected over an eight year period to examine benthic marine faunal biodiversity
      patterns for the continental shelf (55-183 m depth) and slope habitats (184-1280
      m depth) off the US West Coast (47 degrees 20'N-32 degrees 40'N). We specifically
      asked whether marine biodiversity followed a strict latitudinal gradient, and if
      these latitudinal patterns varied across depth, in different benthic substrates,
      and over ecological time scales. Further, we subdivided our study area into three
      smaller regions to test whether coast-wide patterns of biodiversity held at
      regional scales, where local oceanographic processes tend to influence community
      structure and function. Overall, we found complex patterns of biodiversity on
      both the coast-wide and regional scales that differed by taxonomic group.
      Importantly, marine biodiversity was not always highest at low latitudes. We
      found that latitude, depth, substrate, and year were all important descriptors of
      fish and invertebrate diversity. Invertebrate richness and taxonomic diversity
      were highest at high latitudes and in deeper waters. Fish richness also increased
      with latitude, but exhibited a hump-shaped relationship with depth, increasing
      with depth up to the continental shelf break, ~200 m depth, and then decreasing
      in deeper waters. We found relationships between fish taxonomic and functional
      diversity and latitude, depth, substrate, and time at the regional scale, but not
      at the coast-wide scale, suggesting that coast-wide patterns can obscure
      important correlates at smaller scales. Our study provides insight into complex
      diversity patterns of the deep water soft substrate benthic ecosystems off the US
      West Coast. 

PMID- 26308522
TI  - Identifying the Critical Domain of LL-37 Involved in Mediating Neutrophil
      Activation in the Presence of Influenza Virus: Functional and Structural
      Analysis.
AB  - The human cathelicidin LL-37 has been shown to play a role in host defense
      against influenza A viruses (IAV) through direct antiviral effects and through
      modulating inflammatory responses to infection. We recently showed that LL-37
      increases neutrophil respiratory burst and neutrophil extracellular trap (NET)
      responses to IAV through engaging formyl peptide receptor 2 (FPR-2). In this
      paper we show that a fragment of LL-37, GI-20, which is composed of the central
      helical segment of the peptide, has similar effects as LL-37 on neutrophil
      activation. In addition to increasing respiratory burst and NET responses of the
      cells to IAV through an FPR-2 dependent mechanism, it reduces neutrophil IL-8
      production to IAV (also like LL-37). The N-terminal fragment, LL-23, did not have
      similar effects. Both GI-20 and LL-37 increase neutrophil intracellular calcium
      levels and their ability to increase neutrophil activation responses was calcium
      dependent and partially inhibited by pertussis toxin. These studies show that the
      central helix of LL-37 retains the ability of LL-37 to modulate neutrophil
      responses through FPR-2. Based on our findings we developed a homology model of
      FPR-2 and performed docking experiments of LL-37 and GI-20 with the receptor. 

PMID- 26308523
TI  - The introduction of sialendoscopy has significantly contributed to a decreased
      number of excised salivary glands in Denmark.
AB  - Excision has been the treatment of choice in benign non-tumorous obstructive
      disorders of the major salivary glands, when symptoms persisted in spite of
      conservative measures. Unfortunately surgical resection has been associated with
      a relatively high rate of adverse effects. To meet the need for a less invasive
      treatment modality for benign obstructive non-tumorous disorders (i.e., salivary
      stones or stenosis), sialendoscopy has been developed and implemented in several
      countries here among Denmark. This study is a 13-year retrospective registry
      based study using The Danish National Patient Register. ICD-10 codes used for non
      tumorous obstructive disease of the salivary glands were identified and used to
      extract patients potentially eligible for sialendoscopy in order to compare
      sialendoscopic surgery and extirpations of salivary glands. In 2012 sialendoscopy
      accounted for almost 20 % of all surgical interventions on the major salivary
      glands due to benign non-tumorous disease. Nationally and regionally the total
      number of resected major salivary glands due to benign obstructive disease also
      decreased significantly during the study period. A positive outcome, like the
      ones described here, will inspire further development and dissemination of gland
      preserving techniques, to great benefit for the patients. 

PMID- 26308524
TI  - Clinical manifestations in patients with herpes zoster oticus.
AB  - Patients with herpes zoster oticus (HZO) may exhibit diverse symptoms regarding
      cochleovestibular dysfunction. This study investigated the clinical
      manifestations of HZO by comparing symptoms associated with dysfunctions of the
      7th and 8th cranial nerves (CN VII and VIII, respectively). This study is a
      retrospective case series. Eighty-one patients with HZO who had dysfunction of CN
      VII or VIII were included in this study. Electroneuronography (ENoG) values were
      compared among patient groups with facial weakness. Patients with ipsilateral
      facial weakness (62 of 81) were more common than those without. Among 81
      patients, those with facial weakness, hearing loss, and vertigo were most common,
      and only 1 patient had vertigo without hearing loss or facial weakness. Most
      patients with vertigo also had hearing loss (28 of 30), and patients without
      hearing loss did not have vertigo (19 of 21). While patients with vertigo had
      worse ENoG values than those without vertigo, ENoG values were not significantly
      different between patients with and without hearing loss. In conclusion, various
      clinical manifestations of CN VII and VIII dysfunction are possible in patients
      with HZO. Patients with vertigo had worse ENoG values than those without, which
      may indicate that vertigo reflects more severe facial nerve degeneration in HZO
      patients with facial weakness. 

PMID- 26308525
TI  - Baseline Plasma C-Reactive Protein Concentrations and Motor Prognosis in
      Parkinson Disease.
AB  - BACKGROUND: C-reactive protein (CRP), a blood inflammatory biomarker, is
      associated with the development of Alzheimer disease. In animal models of
      Parkinson disease (PD), systemic inflammatory stimuli can promote
      neuroinflammation and accelerate dopaminergic neurodegeneration. However, the
      association between long-term systemic inflammations and neurodegeneration has
      not been assessed in PD patients. OBJECTIVE: To investigate the longitudinal
      effects of baseline CRP concentrations on motor prognosis in PD. DESIGN, SETTING,
      AND PARTICIPANTS: Retrospective analysis of 375 patients (mean age, 69.3 years;
      mean PD duration, 6.6 years). Plasma concentrations of high-sensitivity CRP were
      measured in the absence of infections, and the Unified Parkinson's Disease Rating
      Scale Part III (UPDRS-III) scores were measured at five follow-up intervals (Days
      1-90, 91-270, 271-450, 451-630, and 631-900). MAIN OUTCOME MEASURE: Change of
      UPDRS-III scores from baseline to each of the five follow-up periods. RESULTS:
      Change in UPDRS-III scores was significantly greater in PD patients with CRP
      concentrations >=0.7 mg/L than in those with CRP concentrations <0.7 mg/L, as
      determined by a generalized estimation equation model (P = 0.021) for the entire
      follow-up period and by a generalized regression model (P = 0.030) for the last
      follow-up interval (Days 631-900). The regression coefficients of baseline CRP
      for the two periods were 1.41 (95% confidence interval [CI] 0.21-2.61) and 2.62
      (95% CI 0.25-4.98), respectively, after adjusting for sex, age, baseline UPDRS
      III score, dementia, and incremental L-dopa equivalent dose. CONCLUSION: Baseline
      plasma CRP levels were associated with motor deterioration and predicted motor
      prognosis in patients with PD. These associations were independent of sex, age,
      PD severity, dementia, and anti-Parkinsonian agents, suggesting that subclinical
      systemic inflammations could accelerate neurodegeneration in PD.

PMID- 26308526
TI  - Hypoperfusion of the Adventitial Vasa Vasorum Develops an Abdominal Aortic
      Aneurysm.
AB  - The aortic wall is perfused by the adventitial vasa vasorum (VV). Tissue hypoxia
      has previously been observed as a manifestation of enlarged abdominal aortic
      aneurysms (AAAs). We sought to determine whether hypoperfusion of the adventitial
      VV could develop AAAs. We created a novel animal model of adventitial VV
      hypoperfusion with a combination of a polyurethane catheter insertion and a
      suture ligation of the infrarenal abdominal aorta in rats. VV hypoperfusion
      caused tissue hypoxia and developed infrarenal AAA, which had similar
      morphological and pathological characteristics to human AAA. In human AAA tissue,
      the adventitial VV were stenotic in both small AAAs (30-49 mm in diameter) and in
      large AAAs (> 50 mm in diameter), with the sac tissue in these AAAs being
      ischemic and hypoxic. These results indicate that hypoperfusion of adventitial VV
      has critical effects on the development of infrarenal AAA. 

PMID- 26308527
TI  - Tomato R2R3-MYB Proteins SlANT1 and SlAN2: Same Protein Activity, Different
      Roles.
AB  - Anthocyanins are water-soluble polyphenolic compounds with a high nutraceutical
      value. Despite the fact that cultivated tomato varieties do not accumulate
      anthocyanins in the fruit, the biosynthetic pathway can be activated in the
      vegetative organs by several environmental stimuli. Little is known about the
      molecular mechanisms regulating anthocyanin synthesis in tomato. Here, we carried
      out a molecular and functional characterization of two genes, SlAN2 and SlANT1,
      encoding two R2R3-MYB transcription factors. We show that both can induce ectopic
      anthocyanin synthesis in transgenic tomato lines, including the fruit. However,
      only SlAN2 acts as a positive regulator of anthocyanin synthesis in vegetative
      tissues under high light or low temperature conditions. 

PMID- 26308528
TI  - PARS PLANA VITRECTOMY IN ADVANCED CASES OF VON HIPPEL-LINDAU EYE DISEASE.
AB  - PURPOSE: To investigate spectrum of patients with Von Hippel-Lindau disease (VHL)
      that required pars plana vitrectomy and evaluate anatomical and functional
      outcomes of surgery. METHODS: Twenty-three patients who underwent surgery for
      advanced VHL eye disease were assessed by genetic tests, diagnostic tests for
      systemic lesions, and clinical eye examination. The vitrectomized eyes were
      divided into two groups: with or without retinotomy (group R vs. NR). Functional
      and anatomical outcome was analyzed and compared between the groups. RESULTS: All
      patients had central nervous system hemangioblastomas and 57% had other systemic
      tumors. Point germline mutations, large partial deletions, and complete vhl gene
      deletions were found in 64%, 27%, and 9% of patients, accordingly. Destruction of
      hemangioblastomas by retinotomy, laser, or cryotherapy and anatomical attachment
      of the retina were achieved in all eyes. Preoperative mean distance best
      corrected visual acuity was logarithm of the minimum angle of resolution 2.66
      (20/9,140) in group R and 1.76 (20/1,150) in group NR (P < 0.05). At 6 months
      postoperatively, distance best-corrected visual acuity improved in 20 eyes (83%).
      After over 24 months postoperatively, distance best-corrected visual acuity
      remained better than preoperatively in 36% in the R group and in 70% in the NR
      group of eyes. During 24 months postoperatively in 17 eyes, new retinal capillary
      hemangiomas developed. The mean number of new retinal capillary hemangiomas per
      eye was higher in group R than in group NR (3.14 vs. 0.70; P < 0.01). In group R,
      number of new retinal capillary hemangioblastoma was higher in retinal segments
      where retinotomy was performed (n = 29) than in other areas (n = 13) (P < 0.01).
      CONCLUSION: Advanced VHL eye disease correlates with occurrence of central
      nervous system and systemic lesions. Spectrum of vhl gene mutation in the
      patients corresponds to that of the general VHL population. Pars plana vitrectomy
      in advanced VHL eye disease can improve or preserve visual function, but
      postoperative progression of ocular VHL disease can be accelerated in cases where
      retinotomy is performed.

PMID- 26308529
TI  - OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FEATURES OF DIABETIC RETINOPATHY.
AB  - PURPOSE: To describe the optical coherence tomography angiography features of
      diabetic retinopathy. METHODS: Using a 70 kHz optical coherence tomography and
      the split-spectrum amplitude decorrelation angiography algorithm, 6 mm * 6 mm 3
      dimensional angiograms of the macula of 4 patients with diabetic retinopathy were
      obtained and compared with fluorescein angiography for features cataloged by the
      Early Treatment of Diabetic Retinopathy Study. RESULTS: Optical coherence
      tomography angiography detected enlargement and distortion of the foveal
      avascular zone, retinal capillary dropout, and pruning of arteriolar branches.
      Areas of capillary loss obscured by fluorescein leakage on fluorescein
      angiography were more clearly defined on optical coherence tomography
      angiography. Some areas of focal leakage on fluorescein angiography that were
      thought to be microaneurysms were found to be small tufts of neovascularization
      that extended above the inner limiting membrane. CONCLUSION: Optical coherence
      tomography angiography does not show leakage but can better delineate areas of
      capillary dropout and detect early retinal neovascularization. This new
      noninvasive angiography technology may be useful for routine surveillance of
      proliferative and ischemic changes in diabetic retinopathy.

PMID- 26308530
TI  - INCIDENCE, RISK FACTORS, AND CLINICAL CHARACTERISTICS OF UNEXPLAINED VISUAL LOSS
      AFTER INTRAOCULAR SILICONE OIL FOR MACULA-ON RETINAL DETACHMENT.
AB  - PURPOSE: To investigate the incidence, risk factors, and clinical characteristics
      of unexplained visual loss after macula-on rhegmatogenous retinal detachment
      (RRD). METHODS: Retrospective cohort of patients with primary macula-on
      rhegmatogenous retinal detachment treated by vitrectomy with gas or silicone oil
      (SO) tamponade in 2011 and 2012. Outcome was unexplained visual loss (>2 Snellen
      lines) 2 months after the last vitrectomy. RESULTS: Incidence of unexplained
      visual loss was 0.7% (1/151) in patients treated by gas and 29.7% (11/37) in
      patients treated by SO (P = 0.001). Visual loss occurred both during SO tamponade
      and after removal. Cases underwent optical coherence tomography, perimetry,
      microperimetry, fluorescein angiography, and visual evoked potentials. Patients
      with unexplained visual loss after SO tamponade showed a small scotoma within the
      central 2 degrees  on microperimetry. Duration of SO tamponade was the only
      statistically significant factor related to the incidence of unexplained visual
      loss (P = 0.001). CONCLUSION: Incidence of SO-related visual loss was 30% with
      duration of tamponade as the only risk factor. This study is the first to apply
      microperimetry in these patients, which showed a distinct pattern of a small
      central scotoma. Therefore, microperimetry can be of great value in the
      diagnostic workup of patients with unexplained visual loss after vitrectomy.

PMID- 26308531
TI  - Musashi-2 Silencing Exerts Potent Activity against Acute Myeloid Leukemia and
      Enhances Chemosensitivity to Daunorubicin.
AB  - RNA-binding protein Musashi-2 (Msi2) is known to play a critical role in
      leukemogenesis and contributes to poor clinical prognosis in acute myeloid
      leukemia (AML). However, the effect of Msi2 silencing on treatment for AML still
      remains poorly understood. In this study, we used lentivirus-mediated RNA
      interference targeting Msi2 to investigate the resulting changes in cellular
      processes and the underlying mechanisms in AML cell lines as well as primary AML
      cells isolated from AML patients. We found that Msi2 was highly expressed in AML
      cells, and its depletion inhibited Ki-67 expression and resulted in decreased in
      vitro and in vivo proliferation. Msi2 silencing induced cell cycle arrest in
      G0/G1 phase, with decreased Cyclin D1 and increased p21 expression. Msi2
      silencing induced apoptosis through down-regulation of Bcl-2 expression and up
      regulation of Bax expression. Suppression of Akt, Erk1/2 and p38 phosphorylation
      also contributed to apoptosis mediated by Msi2 silencing. Finally, Msi2 silencing
      in AML cells also enhanced their chemosensitivity to daunorubicin. Conclusively,
      our data suggest that Msi2 is a promising target for gene therapy to optimize
      conventional chemotherapeutics in AML treatment. 

PMID- 26308532
TI  - Gynecomastia in Patients with Prostate Cancer: A Systematic Review.
AB  - INTRODUCTION: Gynecomastia and/or mastodynia is a common medical problem in
      patients receiving antiandrogen (bicalutamide or flutamide) treatment for
      prostate cancer; up to 70% of these patients result to be affected; furthermore,
      this can jeopardise patients' quality of life. AIMS: To systematically review the
      quality of evidence of the current literature regarding treatment options for
      bicalutamide-induced gynecomastia, including efficacy, safety and patients'
      quality of life. METHODS: The PubMed, Medline, Scopus, The Cochrane Library and
      SveMed+ databases were systematically searched between January 1, 2000 and
      December 31, 2014. All searches were undertaken between January and February
      2015. The search phrase used was:"gynecomastia AND treatment AND prostate
      cancer". Two reviewers assessed 762 titles and abstracts identified. The search
      and review process was done in accordance with the PRISMA statement. The PICOS
      (patients, intervention, comparator, outcomes and study design) process was used
      to specify inclusion criteria. Quality of evidence was rated according to GRADE.
      MAIN OUTCOME MEASURES: Primary outcomes were: treatment effects, number of
      complications and side effects. Secondary outcome was: Quality of Life. RESULTS:
      Eleven studies met the inclusion criteria and are analysed in this review. Five
      studies reported pharmacological intervention with tamoxifen and/or anastrozole,
      either as prophylactic or therapeutic treatment. Four studies reported
      radiotherapy as prophylactic and/or therapeutic treatment. Two studies compared
      pharmacological treatment to radiotherapy. Most of the studies were randomized
      with varying risk of bias. According to GRADE, quality of evidence was moderate
      to high. CONCLUSIONS: Bicalutamide-induced gynecomastia and/or mastodynia can
      effectively be managed by oral tamoxifen (10-20 mg daily) or radiotherapy without
      relevant side effects. Prophylaxis or therapeutic treatment with tamoxifen
      results to be more effective than radiotherapy.

PMID- 26308533
TI  - [Imaging guided differentiation of parotid tumors].

PMID- 26308534
TI  - German Roentgen Society Statement on MR Imaging of Patients with Cardiac
      Pacemakers.
AB  - The aim of this paper is to inform physicians, especially radiologists and
      cardiologists, about the technical and electrophysiological background of MR
      imaging of patients with implanted cardiac pacemakers (PM) and to provide
      dedicated clinical practice guidelines how to perform MR exams in this patient
      group. The presence of a conventional PM system is not any more considered an
      absolute contraindication for MR imaging. The prerequisites for MR imaging on
      pacemaker patients include the assessment of the individual risk/benefit ratio as
      well as to obtain full informed consent about the off label character of the
      procedure and all associated risks. Furthermore the use of special PM-related
      (e.g. re-programming of the PM) and MRI-related (e.g. limitation of whole body
      SAR to 2 W/kg) precautions is required and needs to be combined with adequate
      monitoring during MR imaging using continuous pulsoximetry. MR conditional PM
      devices are tested and approved for the use in the MR environment under certain
      conditions, including the field strength and gradient slew rate of the MR system,
      the maximum whole body SAR value and the presence of MR imaging exclusion zones.
      Safe MR imaging of patients with MR conditional PM requires the knowledge of the
      specific conditions of each PM system. If MR imaging within these specific
      conditions cannot be guaranteed in a given patient, the procedure guidelines for
      conventional PM should be used. The complexity of MR imaging of PM patients
      requires close cooperation of radiologists and cardiologists. KEY POINTS:
      Conventional pacemaker systems are no longer an absolute but rather a relative
      contraindication for performing an MR examination. The procedural management of
      conventional pacemaker includes the assessment of the individual risk/benefit
      ratio, comprehensive patient informed consent about specific related risks and
      "off label" use, extensive PM- and MRI-related safety precautions as well as
      adequate monitoring techniques during the MR exam. Decisive for patient safety
      are precise understanding of, and compliance with, the terms of use for the
      specific MR-conditional pacemaker system. If the electrophysiological and MRI
      specific conditions for use of MR-conditional pacemakers are not met or
      compliance with these conditions for use cannot be guaranteed, the device must be
      treated like a conventional pacemaker.

PMID- 26308535
TI  - Age-Dependent D-dimer Cut-off to Avoid Unnecessary CT-Exams for Ruling-out
      Pulmonary Embolism.
AB  - PURPOSE: To evaluate the effect of an age-dependent D-Dimer cut-off in patients
      who underwent a computed tomography pulmonary angiogram (CTPA) for suspected
      pulmonary embolism (PE) Material and Methods: Retrospective application of an age
      dependent D-dimer cut-off (age/100 in patients aged over 50) in 530 consecutive
      patients, both in- and outpatients, aged over 18, who underwent CTPA for
      suspected PE according to the guidelines. RESULTS: The application of an age
      dependent D-dimer cut-off showed a now negative test-result in 17 of 530 patients
      (3.2%). The proportion was 4.1% (17 of 418) in patients aged over 50. None of
      these 17 cases was diagnosed with PE in CTPA, the false-negative rate was 0%. The
      effect could be seen in outpatients (14 of 377 [3.7%]) as well as in inpatients(3
      of 153 [2.0%]) with no statistically significant difference (p > 0.05).
      CONCLUSION: The application of an age-dependent D-dimer cut-off as part of the
      guidline-based algorithm for suspected PE reduced the number of necessary CTPA in
      outpatients as well as in inpatients. KEY POINTS: The application of an age
      dependent D-dimer cut-off reduces the number of CTPA as part of the diagnostic
      algorithm in patients suspected for PENo reduction in diagnostic safety was
      found. The age adjustement performed equally in outpatients and inpatients

PMID- 26308536
TI  - [Councillor Prof. Paul Krause (1871-1934) - pioneer in X-ray diagnostics and
      early victim of the Nazi regime].

PMID- 26308537
TI  - [Obituary for Professor Dr. Karl Heinz Richter].

PMID- 26308546
TI  - Expansion and Compression of Time Correlate with Information Processing in an
      Enumeration Task.
AB  - Perception of temporal duration is subjective and is influenced by factors such
      as attention and context. For example, unexpected or emotional events are often
      experienced as if time subjectively expands, suggesting that the amount of
      information processed in a unit of time can be increased. Time dilation effects
      have been measured with an oddball paradigm in which an infrequent stimulus is
      perceived to last longer than standard stimuli in the rest of the sequence.
      Likewise, time compression for the oddball occurs when the duration of the
      standard items is relatively brief. Here, we investigated whether the amount of
      information processing changes when time is perceived as distorted. On each
      trial, an oddball stimulus of varying numerosity (1-14 items) and duration was
      presented along with standard items that were either short (70 ms) or long (1050
      ms). Observers were instructed to count the number of dots within the oddball
      stimulus and to judge its relative duration with respect to the standards on that
      trial. Consistent with previous results, oddballs were reliably perceived as
      temporally distorted: expanded for longer standard stimuli blocks and compressed
      for shorter standards. The occurrence of these distortions of time perception
      correlated with perceptual processing; i.e. enumeration accuracy increased when
      time was perceived as expanded and decreased with temporal compression. These
      results suggest that subjective time distortions are not epiphenomenal, but
      reflect real changes in sensory processing. Such short-term plasticity in
      information processing rate could be evolutionarily advantageous in optimizing
      perception and action during critical moments. 

PMID- 26308547
TI  - Ultrafine and respirable particle exposure during vehicle fire suppression.
AB  - Vehicle fires are a common occurrence, yet few studies have reported exposures
      associated with burning vehicles. This article presents an assessment of
      firefighters' potential for ultrafine and respirable particle exposure during
      vehicle fire suppression training. Fires were initiated within the engine
      compartment and passenger cabins of three salvaged vehicles, with subsequent
      water suppression by fire crews. Firefighter exposures were monitored with an
      array of direct reading particle and air quality instruments. A flexible metallic
      duct and blower drew contaminants to the instrument array, positioned at a safe
      distance from the burning vehicles, with the duct inlet positioned at the nozzle
      operator's shoulder. The instruments measured the particle number, active surface
      area, respirable particle mass, photoelectric response, aerodynamic particle size
      distributions, and air quality parameters. Although vehicle fires were suppressed
      quickly (<10 minutes), firefighters may be exposed to short duration, high
      particle concentration episodes during fire suppression, which are orders of
      magnitude greater than the ambient background concentration. A maximum transient
      particle concentration of 1.21 * 10(7) particles per cm(3), 170 mg m(-3)
      respirable particle mass, 4700 MUm(2) cm(-3) active surface area and 1400
      (arbitrary units) in photoelectric response were attained throughout the series
      of six fires. Expressed as fifteen minute time-weighted averages, engine
      compartment fires averaged 5.4 * 10(4) particles per cm(3), 0.36 mg m(-3)
      respirable particle mass, 92 MUm(2) cm(-3) active particle surface area and 29
      (arbitrary units) in photoelectric response. Similarly, passenger cabin fires
      averaged 2.04 * 10(5) particles per cm(3), 2.7 mg m(-3) respirable particle mass,
      320 MUm(2) cm(-3) active particle surface area, and 34 (arbitrary units) in
      photoelectric response. Passenger cabin fires were a greater potential source of
      exposure than engine compartment fires. The wind direction and the relative
      position of the fire crew to the stationary burning vehicle played a primary role
      in fire crews' potential for exposure. We recommend that firefighters wear self
      contained breathing apparatus during all phases of the vehicle fire response to
      significantly reduce their potential for particulate, vapor, and gaseous
      exposures. 

PMID- 26308548
TI  - Comparative Analysis and Distribution of Omega-3 lcPUFA Biosynthesis Genes in
      Marine Molluscs.
AB  - Recent research has identified marine molluscs as an excellent source of omega-3
      long-chain polyunsaturated fatty acids (lcPUFAs), based on their potential for
      endogenous synthesis of lcPUFAs. In this study we generated a representative list
      of fatty acyl desaturase (Fad) and elongation of very long-chain fatty acid
      (Elovl) genes from major orders of Phylum Mollusca, through the interrogation of
      transcriptome and genome sequences, and various publicly available databases. We
      have identified novel and uncharacterised Fad and Elovl sequences in the
      following species: Anadara trapezia, Nerita albicilla, Nerita melanotragus,
      Crassostrea gigas, Lottia gigantea, Aplysia californica, Loligo pealeii and
      Chlamys farreri. Based on alignments of translated protein sequences of Fad and
      Elovl genes, the haeme binding motif and histidine boxes of Fad proteins, and the
      histidine box and seventeen important amino acids in Elovl proteins, were highly
      conserved. Phylogenetic analysis of aligned reference sequences was used to
      reconstruct the evolutionary relationships for Fad and Elovl genes separately.
      Multiple, well resolved clades for both the Fad and Elovl sequences were
      observed, suggesting that repeated rounds of gene duplication best explain the
      distribution of Fad and Elovl proteins across the major orders of molluscs. For
      Elovl sequences, one clade contained the functionally characterised Elovl5
      proteins, while another clade contained proteins hypothesised to have Elovl4
      function. Additional well resolved clades consisted only of uncharacterised Elovl
      sequences. One clade from the Fad phylogeny contained only uncharacterised
      proteins, while the other clade contained functionally characterised delta-5
      desaturase proteins. The discovery of an uncharacterised Fad clade is
      particularly interesting as these divergent proteins may have novel functions.
      Overall, this paper presents a number of novel Fad and Elovl genes suggesting
      that many mollusc groups possess most of the required enzymes for the synthesis
      of lcPUFAs.

PMID- 26308549
TI  - Spinal Cord Injury and Migraine Headache: A Population-Based Study.
AB  - Migraine headaches are a common neurological condition, negatively impacting
      health and quality of life. The association between migraines and spinal cord
      injury (SCI) is intriguing to consider from the perspective that migraine
      headaches may be acquired in response to damage in the spinal cord
      [corrected].The primary objective of this study was to further examine the
      association between SCI and migraine headache, controlling for potential
      confounding variables. A secondary objective was to determine the impact of
      migraine headaches on self-perceived health. Data from a sample of 61,047
      participants were obtained from the cross-sectional Canadian Community Health
      Survey. Multivariable logistic regression was used to explore the association
      between SCI and migraine headache using probability weights and adjusting for
      confounders. The multivariable age- and sex-adjusted model revealed a strong
      association between SCI and migraine headache, with an adjusted odds ratio for
      migraine of 4.82 (95% confidence interval [3.02, 7.67]) among those with SCI
      compared to those without SCI. Further, individuals who experienced both SCI and
      migraine tended to report poorer perceived general health compared with the other
      groups (i.e., SCI and no migraine). In conclusion, this study established a
      strong association between SCI and migraine headache. Further research is needed
      to explore the possible mechanisms underlying this relationship. Improvements in
      clinical practice to minimize this issue could result in significant improvements
      in quality of life.

PMID- 26308550
TI  - Nanoscale biophysical properties of the cell surface galactosaminogalactan from
      the fungal pathogen Aspergillus fumigatus.
AB  - Many fungal pathogens produce cell surface polysaccharides that play essential
      roles in host-pathogen interactions. In Aspergillus fumigatus, the newly
      discovered polysaccharide galactosaminogalactan (GAG) mediates adherence to a
      variety of substrates through molecular mechanisms that are poorly understood.
      Here we use atomic force microscopy to unravel the localization and adhesion of
      GAG on living fungal cells. Using single-molecule imaging with tips bearing anti
      GAG antibodies, we found that GAG is massively exposed on wild-type (WT) germ
      tubes, consistent with the notion that this glycopolymer is secreted by the
      mycelium of A. fumigatus, while it is lacking on WT resting conidia and on germ
      tubes from a mutant (Deltauge3) deficient in GAG. Imaging germ tubes with tips
      bearing anti-beta-glucan antibodies shows that exposure of beta-glucan is
      strongly increased in the Deltauge3 mutant, indicating that this polysaccharide
      is masked by GAG during hyphal growth. Single-cell force measurements show that
      expression of GAG on germ tubes promotes specific adhesion to pneumocytes and non
      specific adhesion to hydrophobic substrates. These results provide a molecular
      foundation for the multifunctional adhesion properties of GAG, thus suggesting it
      could be used as a potential target in anti-adhesion therapy and immunotherapy.
      Our methodology represents a powerful approach for characterizing the nanoscale
      organization and adhesion of cell wall polysaccharides during fungal
      morphogenesis, thereby contributing to increase our understanding of their role
      in biofilm formation and immune responses. 

PMID- 26308551
TI  - Changes in Data Sharing and Data Reuse Practices and Perceptions among Scientists
      Worldwide.
AB  - The incorporation of data sharing into the research lifecycle is an important
      part of modern scholarly debate. In this study, the DataONE Usability and
      Assessment working group addresses two primary goals: To examine the current
      state of data sharing and reuse perceptions and practices among research
      scientists as they compare to the 2009/2010 baseline study, and to examine
      differences in practices and perceptions across age groups, geographic regions,
      and subject disciplines. We distributed surveys to a multinational sample of
      scientific researchers at two different time periods (October 2009 to July 2010
      and October 2013 to March 2014) to observe current states of data sharing and to
      see what, if any, changes have occurred in the past 3-4 years. We also looked at
      differences across age, geographic, and discipline-based groups as they currently
      exist in the 2013/2014 survey. Results point to increased acceptance of and
      willingness to engage in data sharing, as well as an increase in actual data
      sharing behaviors. However, there is also increased perceived risk associated
      with data sharing, and specific barriers to data sharing persist. There are also
      differences across age groups, with younger respondents feeling more favorably
      toward data sharing and reuse, yet making less of their data available than older
      respondents. Geographic differences exist as well, which can in part be
      understood in terms of collectivist and individualist cultural differences. An
      examination of subject disciplines shows that the constraints and enablers of
      data sharing and reuse manifest differently across disciplines. Implications of
      these findings include the continued need to build infrastructure that promotes
      data sharing while recognizing the needs of different research communities.
      Moving into the future, organizations such as DataONE will continue to assess,
      monitor, educate, and provide the infrastructure necessary to support such
      complex grand science challenges. 

PMID- 26308552
TI  - Crop Species Diversity Changes in the United States: 1978-2012.
AB  - Anecdotal accounts regarding reduced US cropping system diversity have raised
      concerns about negative impacts of increasingly homogeneous cropping systems.
      However, formal analyses to document such changes are lacking. Using US
      Agriculture Census data, which are collected every five years, we quantified crop
      species diversity from 1978 to 2012, for the contiguous US on a county level
      basis. We used Shannon diversity indices expressed as effective number of crop
      species (ENCS) to quantify crop diversity. We then evaluated changes in county
      level crop diversity both nationally and for each of the eight Farm Resource
      Regions developed by the National Agriculture Statistics Service. During the 34
      years we considered in our analyses, both national and regional ENCS changed.
      Nationally, crop diversity was lower in 2012 than in 1978. However, our analyses
      also revealed interesting trends between and within different Resource Regions.
      Overall, the Heartland Resource Region had the lowest crop diversity whereas the
      Fruitful Rim and Northern Crescent had the highest. In contrast to the other
      Resource Regions, the Mississippi Portal had significantly higher crop diversity
      in 2012 than in 1978. Also, within regions there were differences between
      counties in crop diversity. Spatial autocorrelation revealed clustering of low
      and high ENCS and this trend became stronger over time. These results show that,
      nationally counties have been clustering into areas of either low diversity or
      high diversity. Moreover, a significant trend of more counties shifting to lower
      rather than to higher crop diversity was detected. The clustering and shifting
      demonstrates a trend toward crop diversity loss and attendant homogenization of
      agricultural production systems, which could have far-reaching consequences for
      provision of ecosystem system services associated with agricultural systems as
      well as food system sustainability. 

PMID- 26308553
TI  - Nontoxicity of lentiviral vector infection to viability, migration, apoptosis,
      and differentiation of postnatal rat enteric neural crest-derived cells.
AB  - Lentiviral vector infection of enhanced green fluorescent protein fluorescence
      reporter genes in enteric neural crest-derived cells maintained efficient,
      stable, long-term labeling and the infected enteric neural crest-derived cells
      could survive, proliferate, and express fluorescent reporter genes. However, the
      method does not show whether there is some defined or undefined toxicity to the
      enteric neural crest-derived cells, which may affect enteric neural crest-derived
      cells' properties. Here, we evaluated the enteric neural crest-derived cells
      properties under the influence of lentivirus infection of enhanced green
      fluorescent protein fluorescence reporter genes. This study used the cell count
      kit-8 for measurement of vitality, transwell for cell migration,
      immunocytochemistry for cell count and identification, and tested the apoptosis
      of the enteric neural crest-derived cells with flow cytometry. The enteric neural
      crest-derived cells with or without lentivirus and their derivative enteric
      neural crest-derived cells could form characteristic neurospheres, and maintain
      their level of fluorescent label steady. When cultured under inducing conditions,
      enteric neural crest-derived cells differentiated into neurons and glia. The
      results showed that the enteric neural crest-derived cells with or without
      lentivirus showed no significant difference in viability, migration, apoptosis,
      neuronal, and glial ratio. The study identified that lentivirus can be used in a
      nontoxic manner for infection of enhanced green fluorescent protein fluorescence
      reporter genes into enteric neural crest-derived cells.

PMID- 26308554
TI  - Beneficial effect of Re doping on the electrochemical HER activity of MoS2
      fullerenes.
AB  - Electrochemical generation of hydrogen by non-precious metal electrocatalysts at
      a lower overpotential is a focus area of research directed towards sustainable
      energy. The exorbitant costs associated with Pt-based catalysts is the major
      bottleneck associated with commercial-scale hydrogen generation. Strategies for
      the synthesis of cost-effective and stable catalysts are thus key for a
      prospective 'hydrogen economy'. In this report, we highlight a novel and general
      strategy to enhance the electrochemical activity of molybdenum disulfide (MoS2)
      in a fullerene structure (IF-). In particular, pristine (undoped) and rhenium
      doped nanoparticles of MoS2 with fullerene-like structures (IF-MoS2) were
      studied, and their performance as catalysts for the hydrogen evolution reaction
      (HER) was compared to that of 2H-MoS2 particles (platelets). The current density
      of the IF-MoS2 was higher by one order of magnitude than that of few-layer (FL-)
      MoS2, due to the enhanced density of the edge sites. Furthermore, Re doping of as
      low as 100 ppm in IF-MoS2 decreased the onset potential by 60-80 mV and increased
      the activity by 60 times compared with that of the FL-MoS2. The combined
      synergistic effect of Re doping and the IF structure not only changes the
      intrinsic nature of the MoS2 but also increases its reactivity. This strategy
      highlights the potential use of the IF structure and Re doping in
      electrocatalytic hydrogen evolution using MoS2-based catalysts. 

PMID- 26308555
TI  - Otolaryngology utilization of speech-language pathology services for voice
      disorders.
AB  - OBJECTIVES/HYPOTHESIS: To examine the utilization of speech-language pathology
      (SLP) services by otolaryngology for outpatients with laryngeal/voice disorders.
      STUDY DESIGN: Retrospective analysis of a large, national, administrative US
      claims database. METHODS: The study population included patients with a
      laryngeal/voice disorder based on International Classification of Diseases, Ninth
      Revision, Clinical Modification codes from January 1, 2004 to December 31, 2008,
      seen by an otolaryngologist as an outpatient, and 12 months of follow-up. Data
      were collected on SLP evaluation and treatment and patient factors including age,
      gender, geographic region, employment status, initial laryngeal diagnosis, and
      laryngeal diagnosis change over 12 months. Multivariable logistic regression
      analysis was used to investigate factors associated with receipt of SLP
      evaluation and treatment. RESULTS: There were 91,898 unique patients who met
      study criteria. A total of 4,485 (4.9%) patients had an SLP evaluation, of whom
      2,216 (49.4%) had at least one voice therapy session. Patient age, gender,
      geographic region, and laryngeal diagnosis were associated with increased
      likelihood of receiving SLP services. Patients whose final laryngeal diagnosis
      changed from their initial diagnosis had greater odds of having an SLP evaluation
      (odds ratio = 1.18, 95% confidence interval = 1.06-1.31) compared to patients
      without laryngeal diagnosis change. CONCLUSIONS: SLP evaluation and treatment
      occurred in a minority of laryngeal/voice-disordered patients. Further study is
      needed to assess the impact of SLP services on the healthcare utilization of
      patients with laryngeal/voice disorders. LEVEL OF EVIDENCE: 2C.

PMID- 26308556
TI  - Technical Decision-Making with Higher Order Structure Data: Detecting Reversible
      Concentration-Dependent Self-Association in a Monoclonal Antibody and a
      Preliminary Investigation to Eliminate It.
AB  - Protein self-association or aggregation is a property of significant concern for
      biopharmaceutical products due to the potential ability of aggregates to cause
      adverse toxicological and immunological effects. Thus, during the development of
      a protein biopharmaceutical, it is important to detect and quantify the level and
      nature of aggregate species as early as possible in order to make well-informed
      decisions and to mitigate and control potential risks. Although a deeper
      understanding of the mechanism of aggregation (i.e., protein-protein
      interactions) is desirable, such detailed assessment is not always necessary from
      a biopharmaceutical process development point of view. In fact, the scope of
      characterization efforts is often focused on achieving a well-controlled process,
      which generates a product that reliably meets established acceptance criteria for
      safety and efficacy. In this brief note, we evaluated the utility of size
      exclusion chromatography, dynamic light scattering, and analytical
      ultracentrifugation in their simplest forms, to effectively reveal and confirm
      the presence of concentration-dependent reversible self-association (RSA) in a
      monoclonal antibody in the early stages of formulation development. Using these
      techniques, we also initiated preliminary work aimed at reducing the occurrence
      of this RSA behavior by varying the pH of the formulation buffer.

PMID- 26308558
TI  - Cyclic [2]Catenane Dimers, Trimers, and Tetramers.
AB  - Dimeric, trimeric, and tetrameric cyclic [2]catenanes have been prepared directly
      through one-pot sodium-ion-templated dynamic imine formation from a diamine and a
      tetraaldehyde. NaBH4 mediated reduction of the labile imino bonds of these cyclic
      [2]catenane oligomers, followed by methylation of the resulting secondary amino
      groups enabled the isolation and characterization of oligomeric cyclic
      [2]catenanes as stable, covalently linked compounds. 

PMID- 26308559
TI  - Multichannel-improved charge-carrier dynamics in well-designed hetero
      nanostructural plasmonic photocatalysts toward highly efficient solar-to-fuels
      conversion.
AB  - The charge-carrier dynamics process in well-designed hetero-nanostructural
      plasmonic photocatalysts is greatly improved through a multichannel sensitization
      effect, which therefore results in a significant enhancement of the efficiencies
      of solar-to-fuels conversion. 

PMID- 26308560
TI  - Understanding the mind from an evolutionary perspective: an overview of
      evolutionary psychology.
AB  - The theory of evolution by natural selection provides the only scientific
      explanation for the existence of complex adaptations. The design features of the
      brain, like any organ, are the result of selection pressures operating over deep
      time. Evolutionary psychology posits that the human brain comprises a multitude
      of evolved psychological mechanisms, adaptations to specific and recurrent
      problems of survival and reproduction faced over human evolutionary history.
      Although some mistakenly view evolutionary psychology as promoting genetic
      determinism, evolutionary psychologists appreciate and emphasize the interactions
      between genes and environments. This approach to psychology has led to a richer
      understanding of a variety of psychological phenomena, and has provided a
      powerful foundation for generating novel hypotheses. Critics argue that
      evolutionary psychologists resort to storytelling, but as with any branch of
      science, empirical testing is a vital component of the field, with hypotheses
      standing or falling with the weight of the evidence. Evolutionary psychology is
      uniquely suited to provide a unifying theoretical framework for the disparate
      subdisciplines of psychology. An evolutionary perspective has provided insights
      into several subdisciplines of psychology, while simultaneously demonstrating the
      arbitrary nature of dividing psychological science into such subdisciplines.
      Evolutionary psychologists have amassed a substantial empirical and theoretical
      literature, but as a relatively new approach to psychology, many questions
      remain, with several promising directions for future research. For further
      resources related to this article, please visit the WIREs website. CONFLICT OF
      INTEREST: The authors have declared no conflicts of interest for this article.

PMID- 26308561
TI  - Psychology of knowledge representation.
AB  - Every cognitive enterprise involves some form of knowledge representation. Humans
      represent information about the external world and internal mental states, like
      beliefs and desires, and use this information to meet goals (e.g., classification
      or problem solving). Unfortunately, researchers do not have direct access to
      mental representations. Instead, cognitive scientists design experiments and
      implement computational models to develop theories about the mental
      representations present during task performance. There are several main types of
      mental representation and corresponding processes that have been posited:
      spatial, feature, network, and structured. Each type has a particular structure
      and a set of processes that are capable of accessing and manipulating information
      within the representation. The structure and processes determine what information
      can be used during task performance and what information has not been represented
      at all. As such, the different types of representation are likely used to solve
      different kinds of tasks. For example, structured representations are more
      complex and computationally demanding, but are good at representing relational
      information. Researchers interested in human psychology would benefit from
      considering how knowledge is represented in their domain of inquiry. For further
      resources related to this article, please visit the WIREs website. CONFLICT OF
      INTEREST: The author has declared no conflicts of interest for this article.

PMID- 26308557
TI  - Rescue of deficient amygdala tonic gamma-aminobutyric acidergic currents in the
      Fmr-/y mouse model of fragile X syndrome by a novel gamma-aminobutyric acid type
      A receptor-positive allosteric modulator.
AB  - Alterations in the ratio of excitatory to inhibitory transmission are emerging as
      a common component of many nervous system disorders, including autism spectrum
      disorders (ASDs). Tonic gamma-aminobutyric acidergic (GABAergic) transmission
      provided by peri- and extrasynaptic GABA type A (GABAA ) receptors powerfully
      controls neuronal excitability and plasticity and, therefore, provides a rational
      therapeutic target for normalizing hyperexcitable networks across a variety of
      disorders, including ASDs. Our previous studies revealed tonic GABAergic deficits
      in principal excitatory neurons in the basolateral amygdala (BLA) in the Fmr1(
      /y) knockout (KO) mouse model fragile X syndrome. To correct amygdala deficits in
      tonic GABAergic neurotransmission in Fmr1(-/y) KO mice, we developed a novel
      positive allosteric modulator of GABAA receptors, SGE-872, based on endogenously
      active neurosteroids. This study shows that SGE-872 is nearly as potent and twice
      as efficacious for positively modulating GABAA receptors as its parent molecule,
      allopregnanolone. Furthermore, at submicromolar concentrations (<=1 MUM), SGE-872
      is selective for tonic, extrasynaptic alpha4beta3delta-containing GABAA receptors
      over typical synaptic alpha1beta2gamma2 receptors. We further find that SGE-872
      strikingly rescues the tonic GABAergic transmission deficit in principal
      excitatory neurons in the Fmr1(-/y) KO BLA, a structure heavily implicated in the
      neuropathology of ASDs. Therefore, the potent and selective action of SGE-872 on
      tonic GABAA receptors containing alpha4 subunits may represent a novel and highly
      useful therapeutic avenue for ASDs and related disorders involving
      hyperexcitability of neuronal networks.

PMID- 26308562
TI  - Similarity.
AB  - Similarity is a fundamental concept within Cognitive Science. It is routinely
      invoked in the explanation of cognitive processes as diverse as memory retrieval,
      categorization, visual search, problem solving, learning, language processing,
      reasoning, and social behavior. At the same time, it is of fundamental practical
      concern to computer scientists concerned with clustering and machine learning,
      and it figures in many philosophical contexts. Crucially, 'similar' is not a
      relationship that simply reflects objective properties of the objects under
      consideration but rather is dependent on how those objects are represented by an
      observer. This ties theories of similarity closely to theories of representation.
      For further resources related to this article, please visit the WIREs website.
      CONFLICT OF INTEREST: The authors have declared no conflicts of interest for this
      article.

PMID- 26308563
TI  - Models of language evolution and change.
AB  - In the absence of direct evidence of the emergence of language, the explicitness
      of formal models which allow the exploration of interactions between multiple
      complex adaptive systems has proven to be an important tool. Computational
      simulations have been at the heart of the field of evolutionary linguistics for
      the past two decades, particularly through the language game and iterated
      learning paradigms, but these are now being extended and complemented in a number
      of directions, through formal mathematical models, language-ready robotic agents,
      and experimental simulations in the laboratory. For further resources related to
      this article, please visit the WIREs website. CONFLICT OF INTEREST: The author
      has declared no conflicts of interest for this article.

PMID- 26308564
TI  - Using symbols: developmental perspectives.
AB  - The frequent and fluent use of symbols is a distinguishing characteristic of
      human thought and communication. Symbols free us from the bounds of our own
      direct experience and allow us to learn about the world from others. To use a
      symbol, children need to (1) understand the intention that led to the creation
      and use of the symbol, and (b) how the symbol relates to its referent. For
      example, to use a map, children need to know that it is intended to communicate
      spatial information, and how locations on the map correspond to locations in the
      world. In some cases, even very young children are capable of meeting both
      requirements. For example, infants quickly learn that people intend to
      communicate when they use words. Moreover, they quickly learn the meanings of
      many specific words and the objects or concepts that they stand for. In other
      cases, such as learning to use maps of large-scale space, children may struggle
      to understand what the symbol is intended to communicate and the specific
      relations between elements of the symbol and their referents in the world. Here
      we review the development of children's understanding of words, photographs,
      scale models, maps, and text. We consider when and how children gain insight into
      the communicative intent of each of these symbols and how they learn to establish
      connections between the symbol and what it represents. This review helps to
      integrate research on the development of children's understanding of a variety of
      symbol systems. For further resources related to this article, please visit the
      WIREs website. CONFLICT OF INTEREST: The authors have declared no conflicts of
      interest for this article.

PMID- 26308565
TI  - The binding problem.
AB  - The brain processes information in a distributed manner so that features of the
      sensory input are detected at different sites and subsets of these features are
      integrated into objects. The notion of 'binding' refers to the corresponding
      integration process, leading to perception of these objects as entities, and 'the
      binding problem' either refers to the scientific challenge of identifying
      mechanisms that may achieve binding or to the difficulty that mind and brain may
      have with binding in certain situations. This review concentrates on binding of
      properties in visual perception, but other varieties of the binding problem are
      also mentioned. The binding problem is reviewed from psychological,
      neurobiological, and computational perspectives. For further resources related to
      this article, please visit the WIREs website. CONFLICT OF INTEREST: The author
      has declared no conflicts of interest for this article.

PMID- 26308566
TI  - Experimental and theoretical models of human cultural evolution.
AB  - The modern field of cultural evolution is now over 30 years old, and an extensive
      body of theory and data has been amassed. This article reviews models of cultural
      evolution, both experimental and theoretical, and surveys what they can tell us
      about cultural evolutionary processes. The models are grouped according to which
      of four broad questions they address: (1) How are cultural traits changed during
      transmission? (2) How and why do cultural traits accumulate over time? (3) What
      social learning biases do people use? and (4) What are the population-level
      consequences of different social learning biases? We conclude by highlighting
      gaps in the literature and promising future research directions, including the
      further integration of theoretical models and experimental data, the
      identification of the factors underlying cumulative cultural evolution, and the
      explanation of individual and cultural variation in social learning biases. For
      further resources related to this article, please visit the WIREs website.
      CONFLICT OF INTEREST: The authors have declared no conflicts of interest for this
      article.

PMID- 26308567
TI  - Revisiting domain-general accounts of category specificity in mind and brain.
AB  - Theories about the neural basis of semantic knowledge have been strongly
      influenced by reports that particular semantic categories can be differentially
      impaired by neuropathology and can differentially activate particular regions of
      cortex in brain imaging studies. One well-known interpretation of these data is
      that the brain has evolved distinct functional and anatomical modules for storing
      and retrieving knowledge about different kinds of things. We review the evidence
      supporting an alternative view: that category specificity arises from many
      heterogeneous factors and so tells us little directly about the cognitive and
      neural architecture of semantic memory. We consider four general hypotheses about
      domain-general causes of category-specific patterns, their roots in early work,
      and their reemergence in contemporary research. We argue that there is compelling
      evidence supporting each hypothesis, and that the different hypotheses together
      can explain most of the interesting data. We further suggest that such a
      multifactor domain-general approach to category specificity is appealing partly
      because it explains the important findings with reference to theoretical claims
      that are already widely accepted, and partly because it resolves several puzzles
      that arise under the alternative view. For further resources related to this
      article, please visit the WIREs website. CONFLICT OF INTEREST: The authors have
      declared no conflicts of interest for this article.

PMID- 26308568
TI  - Cognitive ecology: ecological factors, life-styles, and cognition.
AB  - Cognitive ecology integrates cognition, ecology, and neurobiology in one topic
      and has recently broadened into an exciting diversity of themes covering the
      entire range of cognition and ecological conditions. The review identifies three
      major environmental factors interacting with cognition: environmental variation
      (predictable and unpredictable), environmental complexity and predation.
      Generally, variable environments favor cognitive abilities such as exploration,
      learning, innovation, memory and also result in larger brains as compared to
      stable environments. Likewise, cognition is enhanced in complex versus simple
      environments, whereas the relationship between predation and cognitive abilities
      can be positive or negative. However, organisms have often evolved entire life
      styles (e.g., residency versus migration, food-caching versus noncaching,
      generalism versus specialism) to deal with these environmental factors.
      Considering cognition within this framework provides a much more diverse picture
      of how cognitive abilities evolved in conjunction with other adaptations to
      environmental challenges. This integrated approach identifies gaps of knowledge
      and allows the formulation of hypotheses for future testing. Several recently
      emerged approaches study cognitive abilities at a new and in part highly
      integrated level. For example, the effect that environment has on the development
      of cognitive abilities during ontogeny will improve our understanding about cause
      and effect and gene-environment interactions. Together with two recently emerged
      highly integrative approaches that link personality and pace-of-life syndromes
      with cognitive ecology these new directions will improve insight how cognition is
      interlinked with other major organizational processes. For further resources
      related to this article, please visit the WIREs website. CONFLICT OF INTEREST:
      The author has declared no conflicts of interest for this article.

PMID- 26308569
TI  - Corvid cognition.
AB  - Numerous myths and legends across the world have suggested that corvids are
      intelligent. However, it is only in the last two decades that their cognition has
      become the subject of serious scientific investigation. Here I review what we
      currently know about the temporal, social, and physical cognition of this group.
      I argue that, while the work to date establishes corvids as one of the most
      intelligent groups of animals on the planet, the real scientific potential of the
      Corvidae has yet to be realized. However, a novel 'signature-testing'
      experimental approach is required if we want to unlock this group's promise and
      gain insights into the evolution of human and animal minds. For further resources
      related to this article, please visit the WIREs website. CONFLICT OF INTEREST:
      The authors have declared no conflicts of interest for this article.

PMID- 26308573
TI  - Splenic vasculitis, thrombosis, and infarction in a febrile dog infected with
      Bartonella henselae.
AB  - OBJECTIVE: To describe the clinical course and successful management of a febrile
      dog with polyarthritis, splenic vasculitis, thrombosis, and infarction that was
      infected with Bartonella henselae. CASE SUMMARY: An 8-year-old female spayed
      Labrador Retriever was referred to The Ohio State University Veterinary Medical
      Center Emergency Service for evaluation of limping, fever, vomiting, and malaise
      of 4 days' duration. Physical examination abnormalities included generalized
      weakness, diminished conscious proprioception, bilateral temporalis muscle
      atrophy, and diarrhea. Peripheral lymph nodes were normal, and there were no
      signs of abdominal organomegaly, joint effusion, or spinal pain. Abdominal
      ultrasound identified a nonocclusive splenic vein thrombus. Fine-needle aspirates
      of the spleen revealed pyogranulomatous inflammation, mild reactive lymphoid
      hyperplasia, and mild extramedullary hematopoiesis. Splenic histopathology found
      marked, multifocal to coalescing acute coagulation necrosis (splenic infarctions)
      and fibrinoid necrotizing vasculitis. Bartonella henselae DNA was amplified by
      polymerase chain reaction and sequenced from the splenic tissue. The dog
      responded favorably to antimicrobials and was healthy at the time of follow-up
      evaluation. NEW AND UNIQUE INFORMATION PROVIDED: Bartonella henselae is an
      incompletely characterized emerging canine pathogen. This case report establishes
      a potential role for this bacterium as a cause of vasculitis and thromboembolism,
      which have not been previously reported in association with B. henselae infection
      in dogs.

PMID- 26308574
TI  - Protein/peptide-based entry/fusion inhibitors as anti-HIV therapies: challenges
      and future direction.
AB  - The failures of several first-generation and second-generation small molecule
      drug-based anti-HIV therapies in various stages of clinical trials are an
      indication that there is a need for a paradigm shift in the future designs of
      anti-HIV therapeutics. Over the past several decades, various anti-HIV drugs have
      been developed, among them, protein/peptide-based therapies. From the first
      peptide discovered (SJ2176) to the first peptide approved by the Food and Drug
      Administration (DP178/T20/enfuvirtide/Fuzeon(r)), anti-HIV proteins/peptides as
      fusion/entry inhibitors have been shown to provide potent effects and benefits.
      This review summarizes the past and current endeavors in this area, discusses the
      potential mechanisms of action for various anti-HIV proteins/peptides, compares
      the advantages and disadvantages between the different proteins/peptides, and
      finally, examines the future direction of the field, specifically, strategies
      that will enhance the therapeutic efficacy of fusion/entry inhibitor-based anti
      HIV proteins/peptides. Although there are numerous reviews highlighting the
      general field of entry/fusion inhibitors, there is a lack of literature focused
      on protein/peptide-based entry/fusion inhibitors for HIV therapy, and as a
      result, this review is intended to fill this void by summarizing the past,
      current, and future development of these macromolecules. Copyright (c) 2015 John
      Wiley & Sons, Ltd.

PMID- 26308571
TI  - Simultaneous multislice (SMS) imaging techniques.
AB  - Simultaneous multislice imaging (SMS) using parallel image reconstruction has
      rapidly advanced to become a major imaging technique. The primary benefit is an
      acceleration in data acquisition that is equal to the number of simultaneously
      excited slices. Unlike in-plane parallel imaging this can have only a marginal
      intrinsic signal-to-noise ratio penalty, and the full acceleration is attainable
      at fixed echo time, as is required for many echo planar imaging applications.
      Furthermore, for some implementations SMS techniques can reduce radiofrequency
      (RF) power deposition. In this review the current state of the art of SMS imaging
      is presented. In the Introduction, a historical overview is given of the history
      of SMS excitation in MRI. The following section on RF pulses gives both the
      theoretical background and practical application. The section on encoding and
      reconstruction shows how the collapsed multislice images can be disentangled by
      means of the transmitter pulse phase, gradient pulses, and most importantly using
      multichannel receiver coils. The relationship between classic parallel imaging
      techniques and SMS reconstruction methods is explored. The subsequent section
      describes the practical implementation, including the acquisition of reference
      data, and slice cross-talk. Published applications of SMS imaging are then
      reviewed, and the article concludes with an outlook and perspective of SMS
      imaging.

PMID- 26308576
TI  - Communicating anticancer treatment cessation and transition to palliative care:
      The need for a comprehensive and culturally relevant, person-centered approach.

PMID- 26308575
TI  - Aberrant amino acid signaling promotes growth and metastasis of hepatocellular
      carcinomas through Rab1A-dependent activation of mTORC1 by Rab1A.
AB  - mTORC1 is a master regulator of cell growth and proliferation, and an established
      anticancer drug target. Aberrant mTORC1 signaling is common in hepatocellular
      carcinoma (HCC), but the underlying mechanism remains elusive. Rab1A is a newly
      identified mTORC1 activator that mediates an alternative amino acid (AA)
      signaling branch to Rag GTPases. Because liver is a physiological hub for
      nutrient sensing and metabolic homeostasis, we investigated the possible role of
      Rab1A in HCC. We found that Rab1A is frequently overexpressed in HCC, which
      enhances hyperactive AA-mTORC1 signaling, promoting malignant growth and
      metastasis of HCC in vitro and in vivo. Moreover, aberrant Rab1A expression is
      closely associated with poor prognosis. Strikingly, aberrant Rab1A overexpression
      leads to increased rapamycin sensitivity, indicating that inappropriate
      activation of AA signaling is a cancer-driving event in HCC. Our findings further
      suggest that Rab1A is a valuable biomarker for prognosis and personalized mTORC1
      targeted therapy in liver cancer. 

PMID- 26308577
TI  - Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy: A
      Better Approach to Treat Patients With Extensive Liver Disease.

PMID- 26308578
TI  - Rapid learning in visual cortical networks.
AB  - Although changes in brain activity during learning have been extensively examined
      at the single neuron level, the coding strategies employed by cell populations
      remain mysterious. We examined cell populations in macaque area V4 during a rapid
      form of perceptual learning that emerges within tens of minutes. Multiple single
      units and LFP responses were recorded as monkeys improved their performance in an
      image discrimination task. We show that the increase in behavioral performance
      during learning is predicted by a tight coordination of spike timing with local
      population activity. More spike-LFP theta synchronization is correlated with
      higher learning performance, while high-frequency synchronization is unrelated
      with changes in performance, but these changes were absent once learning had
      stabilized and stimuli became familiar, or in the absence of learning. These
      findings reveal a novel mechanism of plasticity in visual cortex by which
      elevated low-frequency synchronization between individual neurons and local
      population activity accompanies the improvement in performance during learning. 

PMID- 26308579
TI  - Unified pre- and postsynaptic long-term plasticity enables reliable and flexible
      learning.
AB  - Although it is well known that long-term synaptic plasticity can be expressed
      both pre- and postsynaptically, the functional consequences of this arrangement
      have remained elusive. We show that spike-timing-dependent plasticity with both
      pre- and postsynaptic expression develops receptive fields with reduced
      variability and improved discriminability compared to postsynaptic plasticity
      alone. These long-term modifications in receptive field statistics match recent
      sensory perception experiments. Moreover, learning with this form of plasticity
      leaves a hidden postsynaptic memory trace that enables fast relearning of
      previously stored information, providing a cellular substrate for memory savings.
      Our results reveal essential roles for presynaptic plasticity that are missed
      when only postsynaptic expression of long-term plasticity is considered, and
      suggest an experience-dependent distribution of pre- and postsynaptic strength
      changes. 

PMID- 26308580
TI  - Distinct regulation of dopamine D2S and D2L autoreceptor signaling by calcium.
AB  - D2 autoreceptors regulate dopamine release throughout the brain. Two isoforms of
      the D2 receptor, D2S and D2L, are expressed in midbrain dopamine neurons.
      Differential roles of these isoforms as autoreceptors are poorly understood. By
      virally expressing the isoforms in dopamine neurons of D2 receptor knockout mice,
      this study assessed the calcium-dependence and drug-induced plasticity of D2S and
      D2L receptor-dependent G protein-coupled inwardly rectifying potassium (GIRK)
      currents. The results reveal that D2S, but not D2L receptors, exhibited calcium
      dependent desensitization similar to that exhibited by endogenous autoreceptors.
      Two pathways of calcium signaling that regulated D2 autoreceptor-dependent GIRK
      signaling were identified, which distinctly affected desensitization and the
      magnitude of D2S and D2L receptor-dependent GIRK currents. Previous in vivo
      cocaine exposure removed calcium-dependent D2 autoreceptor desensitization in
      wild type, but not D2S-only mice. Thus, expression of D2S as the exclusive
      autoreceptor was insufficient for cocaine-induced plasticity, implying a
      functional role for the co-expression of D2S and D2L autoreceptors. 

PMID- 26308581
TI  - Nemo-like kinase is a novel regulator of spinal and bulbar muscular atrophy.
AB  - Spinal and bulbar muscular atrophy (SBMA) is a progressive neuromuscular disease
      caused by polyglutamine expansion in the androgen receptor (AR) protein. Despite
      extensive research, the exact pathogenic mechanisms underlying SBMA remain
      elusive. In this study, we present evidence that Nemo-like kinase (NLK) promotes
      disease pathogenesis across multiple SBMA model systems. Most remarkably, loss of
      one copy of Nlk rescues SBMA phenotypes in mice, including extending lifespan. We
      also investigated the molecular mechanisms by which NLK exerts its effects in
      SBMA. Specifically, we have found that NLK can phosphorylate the mutant
      polyglutamine-expanded AR, enhance its aggregation, and promote AR-dependent gene
      transcription by regulating AR-cofactor interactions. Furthermore, NLK modulates
      the toxicity of a mutant AR fragment via a mechanism that is independent of AR
      mediated gene transcription. Our findings uncover a crucial role for NLK in
      controlling SBMA toxicity and reveal a novel avenue for therapy development in
      SBMA. 

PMID- 26308582
TI  - Phase-amplitude coupling supports phase coding in human ECoG.
AB  - Prior studies have shown that high-frequency activity (HFA) is modulated by the
      phase of low-frequency activity. This phenomenon of phase-amplitude coupling
      (PAC) is often interpreted as reflecting phase coding of neural representations,
      although evidence for this link is still lacking in humans. Here, we show that
      PAC indeed supports phase-dependent stimulus representations for categories. Six
      patients with medication-resistant epilepsy viewed images of faces, tools,
      houses, and scenes during simultaneous acquisition of intracranial recordings.
      Analyzing 167 electrodes, we observed PAC at 43% of electrodes. Further
      inspection of PAC revealed that category specific HFA modulations occurred at
      different phases and frequencies of the underlying low-frequency rhythm,
      permitting decoding of categorical information using the phase at which HFA
      events occurred. These results provide evidence for categorical phase-coded
      neural representations and are the first to show that PAC coincides with phase
      dependent coding in the human brain. 

PMID- 26308583
TI  - Expression-Enhanced Fluorescent Proteins Based on Enhanced Green Fluorescent
      Protein for Super-resolution Microscopy.
AB  - "Smart fluorophores", such as reversibly switchable fluorescent proteins, are
      crucial for advanced fluorescence imaging. However, only a limited number of such
      labels is available, and many display reduced biological performance compared to
      more classical variants. We present the development of robustly photoswitchable
      variants of enhanced green fluorescent protein (EGFP), named rsGreens, that
      display up to 30-fold higher fluorescence in E. coli colonies grown at 37 
      degrees C and more than 4-fold higher fluorescence when expressed in HEK293T
      cells compared to their ancestor protein rsEGFP. This enhancement is not due to
      an intrinsic increase in the fluorescence brightness of the probes, but rather
      due to enhanced expression levels that allow many more probe molecules to be
      functional at any given time. We developed rsGreens displaying a range of
      photoswitching kinetics and show how these can be used for multimodal diffraction
      unlimited fluorescence imaging such as pcSOFI and RESOLFT, achieving a spatial
      resolution of ~70 nm. By determining the first ever crystal structures of a
      negative reversibly switchable FP derived from Aequorea victoria in both the "on"
      and "off"-conformation we were able to confirm the presence of a cis-trans
      isomerization and provide further insights into the mechanisms underlying the
      photochromism. Our work demonstrates that genetically encoded "smart
      fluorophores" can be readily optimized for biological performance and provides a
      practical strategy for developing maturation- and stability-enhanced photochromic
      fluorescent proteins. 

PMID- 26308584
TI  - Endothelial Cells Promote Pigmentation through Endothelin Receptor B Activation.
AB  - Findings of increased vascularization in melasma lesions and hyperpigmentation in
      acquired bilateral telangiectatic macules suggested a link between pigmentation
      and vascularization. Using high-magnification digital epiluminescence
      dermatoscopy, laser confocal microscopy, and histological examination, we showed
      that benign vascular lesions of the skin have restricted but significant
      hyperpigmentation compared with the surrounding skin. We then studied the role of
      microvascular endothelial cells in regulating skin pigmentation using an in vitro
      co-culture model using endothelial cells and melanocytes. These experiments
      showed that endothelin 1 released by microvascular endothelial cells induces
      increased melanogenesis signaling, characterized by microphthalmia-associated
      transcription factor phosphorylation, and increased tyrosinase and dopachrome
      tautomerase levels. Immunostaining for endothelin 1 in vascular lesions confirmed
      the increased expression on the basal layer of the epidermis above small vessels
      compared with perilesional skin. Endothelin acts through the activation of
      endothelin receptor B and the mitogen-activated protein kinase, extracellular
      signal-regulated kinase (ERK)1/2, and p38, to induce melanogenesis. Finally,
      culturing of reconstructed skin with microvascular endothelial cells led to
      increased skin pigmentation that could be prevented by inhibiting EDNRB. Taken
      together these results demonstrated the role of underlying microvascularization
      in skin pigmentation, a finding that could open new fields of research for
      regulating physiological pigmentation and for treating pigmentation disorders
      such as melasma. 

PMID- 26308585
TI  - Analysis of the Proteome of the Marine Diatom Phaeodactylum tricornutum Exposed
      to Aluminum Providing Insights into Aluminum Toxicity Mechanisms.
AB  - Trace aluminum (Al) concentrations can be toxic to marine phytoplankton, the
      basis of the marine food web, but the fundamental Al toxicity and detoxification
      mechanisms at the molecular levels are poorly understood. Using an array of
      proteomic, transcriptomic, and biochemical techniques, we describe in detail the
      cellular response of the model marine diatom Phaeodactylum tricornutum to a short
      term sublethal Al stress (4 h of exposure to 200 MUM total initial Al). A total
      of 2204 proteins were identified and quantified by isobaric tags for relative and
      absolute quantification (iTRAQ) in response to the Al stress. Among them, 87 and
      78 proteins performing various cell functions were up- and down-regulated after
      Al treatment, respectively. We found that photosynthesis was a key Al toxicity
      target. The Al-induced decrease in electron transport rates in thylakoid
      membranes lead to an increase in reactive oxygen species (ROS) production, which
      cause increased lipid peroxidation. Several ROS-detoxifying proteins were induced
      to help decrease Al-induced oxidative stress. In parallel, glycolysis and pentose
      phosphate pathway were up-regulated in order to produce cell energy (NADPH, ATP)
      and carbon skeleton for cell growth, partially circumventing the Al-induced
      toxicity effects on photosynthesis. These cellular responses to Al stress were
      coordinated by the activation of various signal transduction pathways. The
      identification of Al-responsive proteins in the model marine phytoplankton P.
      tricornutum provides new insights on Al stress responses as well as a good start
      for further exploring Al detoxification mechanisms. 

PMID- 26308586
TI  - Predictors of token-to-token inconsistency in preschool children with typical
      speech-language development.
AB  - The purpose of this study was to examine potential concurrent predictors and
      replicate rates of token-to-token inconsistency (inconsistency in repeated
      productions of the same word) in 43 children with typical speech-language
      development, ages 2;6 to 4;2. A standard linear regression was used to determine
      which variables, if any, among age, expressive and receptive vocabulary, and
      speech sound production abilities predicted token-to-token inconsistency.
      Inconsistency rates in children from one research site, reported elsewhere, were
      compared to rates in children from a second research site. The results revealed
      that expressive vocabulary was the only significant predictor of token-to-token
      inconsistency in these children. Furthermore, inconsistency rates were similarly
      high across the two research sites. The findings are discussed in terms of their
      implications for our theoretical understanding of token-to-token inconsistency
      and its role in the differential diagnosis of speech sound disorders in children.

PMID- 26308587
TI  - Palladium-Catalyzed Oxidative Direct C3- and C7-Alkenylations of Indazoles:
      Application to the Synthesis of Gamendazole.
AB  - The first palladium-catalyzed oxidative alkenylation of (1H)- and (2H)-indazole
      derivatives with various olefins is described. The use of Pd(OAc)2 as the
      catalyst and Ag2CO3 as the oxidant promoted the selective C3-monoalkenylation of
      (1H)-indazoles and (2H)-indazoles, affording the desired products in good yields.
      An original oxidative C7-alkenylation of 3-substituted (1H)-indazoles was also
      developed. The oxidative alkenylation of (1H)-indazole was successfully applied
      to the total synthesis of the drug candidate gamendazole in a step- and atom
      economical fashion. 

PMID- 26308589
TI  - Phenolic natural products of the wines obtained from three new Merlot clone
      candidates.
AB  - This work aimed to evaluate the total contents of polyphenolics (the Ribereau
      Gayon-Maurie procedure), anthocyanins (using pH differential method) and tannins
      (the Negre procedure) as well as the content of phenolic acids (using UPLC/MS
      chromatography), respectively of the wines obtained from three new Merlot clone
      candidates in the perennial clonal selection. The aforementioned chemical
      parameters were determined in the samples covering the period 2009-2012. In
      comparison both with the standard Merlot wine (mother vine) and the wines
      obtained from other two clone candidates, the Merlot wine of the clone candidate
      No. 022 was found to have the highest total content of all three examined
      components 1.89 +/- 0.05 g/L (polyphenolics), 185.59 +/- 5.00 mg/L (anthocyanins)
      and 1.11 +/- 0.03 g/L (tannins), as well as six phenolic acids including gallic
      acid (25.49 +/- 0.27 mg/L). These findings are in good agreement with the
      observed trend for the viticultural parameters indicating the clone candidate No.
      022 as more promising than mother.

PMID- 26308588
TI  - Residential treatment outcomes for adolescents with obsessive-compulsive
      disorder.
AB  - OBJECTIVE: We examined outcomes from a residential treatment program emphasizing
      exposure and response prevention (ERP) to determine if the typically robust
      response to this treatment in outpatient settings extends to patients treated in
      this unique context. METHOD: One hundred and seventy-two adolescents with primary
      Obsessive-compulsive disorder (OCD) completed measures at admission and
      discharge. Almost all (92.4%) participants had at least two diagnoses and nearly
      half (44.2%) had three or more. Treatment consisted of intensive ERP (i.e.,
      approximately 26.5 hr per week), additional cognitive behavioral therapy
      interventions, and medication management within a residential setting. In
      contrast to the samples reported on in the vast majority of other pediatric OCD
      trials, participants in the current study were living apart from their families
      and were immersed within the treatment setting, with staff members available at
      all times. RESULTS: Paired sample t-tests revealed significant decreases in OCD
      and depression severity. CONCLUSIONS: Results suggest that residential treatment
      for adolescents with OCD using a multimodal approach emphasizing ERP can be
      effective for complex cases with significant comorbidity. Results were comparable
      with several randomized controlled trials.

PMID- 26308590
TI  - Monitoring Training Adaptation With a Submaximal Running Test Under Field
      Conditions.
AB  - Regular monitoring of adaptation to training is important for optimizing training
      load and recovery, which is the main factor in successful training. PURPOSE: To
      investigate the usefulness of a novel submaximal running test (SRT) in field
      conditions in predicting and tracking changes of endurance performance. METHODS:
      Thirty-five endurance-trained men and women (age 20-55 y) completed the 18-wk
      endurance-training program. A maximal incremental running test was performed at
      weeks 0, 9, and 18 for determination of maximal oxygen consumption (VO2max) and
      running speed (RS) at exhaustion (RSpeak) and lactate thresholds (LTs). In
      addition, the subjects performed weekly a 3-stage SRT including a postexercise
      heart-rate-recovery (HRR) measurement. The subjects were retrospectively grouped
      into 4 clusters according to changes in SRT results. RESULTS: Large correlations
      (r = .60-.89) were observed between RS during all stages of SRT and all endurance
      performance variables (VO2max, RSpeak, RS at LT2, and RS at LT1). HRR correlated
      only with VO2max (r = .46). Large relationships were also found between changes
      in RS during 80% and 90% HRmax stages of SRT and a change of RSpeak (r = .57, r =
      .79). In addition, the cluster analysis revealed the different trends in RS
      during 80% and 90% stages during the training between the clusters, which showed
      different improvements in VO2max and RSpeak. CONCLUSIONS: The current SRT showed
      great potential as a practical tool for regular monitoring of individual
      adaptation to endurance training without time-consuming and expensive laboratory
      tests.

PMID- 26308592
TI  - Occurrence of copper-resistant strains and a shift in Xanthomonas spp. causing
      tomato bacterial spot in Ontario.
AB  - Field strains of tomato bacterial spot pathogen (Xanthomonas euvesicatoria, X.
      vesicatoria, X. perforans, and X. gardneri) were characterized for sensitivity to
      copper and species composition. A total of 98 strains were isolated from
      symptomatic leaf and fruit samples collected from 18 tomato fields in Ontario. In
      greenhouse pathogenicity tests, most of the field strains caused severe (37
      strains) to highly severe (23 strains) symptoms on 'Bonny Best' tomato plants,
      whereas 38 strains caused moderate symptoms. In MGY agar plates amended with
      various concentrations of copper sulfate, 11 strains were completely sensitive
      (no growth) and 87 strains were resistant (grew on 1.0 mmol/L or higher copper
      concentration). PCR analysis of the hrp gene cluster followed by restriction
      digestion with HaeIII and sequencing identified X. gardneri (35 strains) and X.
      perforans (26 strains) as predominant species and X. euvesicatoria and X.
      vesicatoria as less common species in Ontario tomato fields. Separation of field
      strains into various species was also confirmed with starch hydrolysis activity
      on agar medium. Moreover, 72 field strains produced shiny greenish-yellow
      colonies surrounded by a milky zone on xanthomonad differential (Xan-D) medium,
      and the colonies of 26 strains did not produce a milky zone. Thirty-four strains
      could not be clustered into any species and 25 of those strains were negative for
      the hrp gene PCR and also did not produce a milky zone around colonies on Xan-D
      medium. Our results suggest a widespread existence of copper-resistant strains
      and an increase in X. perforans strains of bacterial spot pathogen in Ontario.
      This information on copper resistance and species composition within bacterial
      spot pathogens in Ontario will be helpful for developing effective disease
      management strategies, making cultivar selection, and breeding new tomato
      cultivars. 

PMID- 26308593
TI  - Catalyst-Free, Selective Growth of ZnO Nanowires on SiO2 by Chemical Vapor
      Deposition for Transfer-Free Fabrication of UV Photodetectors.
AB  - Catalyst-free, selective growth of ZnO nanowires directly on the commonly used
      dielectric SiO2 layer is of both scientific significance and application
      importance, yet it is still a challenge. Here, we report a facile method to grow
      single-crystal ZnO nanowires on a large scale directly on SiO2/Si substrate
      through vapor-solid mechanism without using any predeposited metal catalyst or
      seed layer. We found that a rough SiO2/Si substrate surface created by the
      reactive ion etching is critical for ZnO growth without using catalyst. ZnO
      nanowire array exclusively grows in area etched by the reactive ion etching
      method. The advantages of this method include facile and safe roughness-assisted
      catalyst-free growth of ZnO nanowires on SiO2/Si substrate and the subsequent
      transfer-free fabrication of electronic or optoelectronic devices. The ZnO
      nanowire UV photodetector fabricated by a transfer-free process presented high
      performance in responsivity, quantum efficiency and response speed, even without
      any post-treatments. The strategy shown here would greatly reduce the complexity
      in nanodevice fabrication and give an impetus to the application of ZnO nanowires
      in nanoelectronics and optoelectronics. 

PMID- 26308594
TI  - Monoclonal Antibodies in Multiple Myeloma Come of Age.

PMID- 26308595
TI  - Mandatory Medicare Bundled Payment--Is It Ready for Prime Time?

PMID- 26308596
TI  - Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma.
AB  - BACKGROUND: Multiple myeloma cells uniformly overexpress CD38. We studied
      daratumumab, a CD38-targeting, human IgG1kappa monoclonal antibody, in a phase 1
      2 trial involving patients with relapsed myeloma or relapsed myeloma that was
      refractory to two or more prior lines of therapy. METHODS: In part 1, the dose
      escalation phase, we administered daratumumab at doses of 0.005 to 24 mg per
      kilogram of body weight. In part 2, the dose-expansion phase, 30 patients
      received 8 mg per kilogram of daratumumab and 42 received 16 mg per kilogram,
      administered once weekly (8 doses), twice monthly (8 doses), and monthly for up
      to 24 months. End points included safety, efficacy, and pharmacokinetics.
      RESULTS: No maximum tolerated dose was identified in part 1. In part 2, the
      median time since diagnosis was 5.7 years. Patients had received a median of four
      prior treatments; 79% of the patients had disease that was refractory to the last
      therapy received (64% had disease refractory to proteasome inhibitors and
      immunomodulatory drugs and 64% had disease refractory to bortezomib and
      lenalidomide), and 76% had received autologous stem-cell transplants. Infusion
      related reactions in part 2 were mild (71% of patients had an event of any grade,
      and 1% had an event of grade 3), with no dose-dependent adverse events. The most
      common adverse events of grade 3 or 4 (in >= 5% of patients) were pneumonia and
      thrombocytopenia. The overall response rate was 36% in the cohort that received
      16 mg per kilogram (15 patients had a partial response or better, including 2
      with a complete response and 2 with a very good partial response) and 10% in the
      cohort that received 8 mg per kilogram (3 had a partial response). In the cohort
      that received 16 mg per kilogram, the median progression-free survival was 5.6
      months (95% confidence interval [CI], 4.2 to 8.1), and 65% (95% CI, 28 to 86) of
      the patients who had a response did not have progression at 12 months.
      CONCLUSIONS: Daratumumab monotherapy had a favorable safety profile and
      encouraging efficacy in patients with heavily pretreated and refractory myeloma.
      (Funded by Janssen Research and Development and Genmab; ClinicalTrials.gov
      number, NCT00574288.).

PMID- 26308597
TI  - Therapeutic efficacy of PD-L1 blockade in a breast cancer model is enhanced by
      cellular vaccines expressing B7-1 and glycolipid-anchored IL-12.
AB  - Immunotherapeutic approaches have emerged as promising strategies to treat
      various cancers, including breast cancer. A single approach, however, is unlikely
      to effectively combat the complex, immune evasive strategies found within the
      tumor microenvironment, thus novel, effective combination treatments must be
      explored. In this study, we investigated the efficacy of a combination therapy
      consisting of PD-L1 immune checkpoint blockade and whole cell vaccination in a
      HER-2 positive mouse model of breast cancer. We demonstrate that tumorigenicity
      is completely abrogated when adjuvanted with immune stimulatory molecules (ISMs)
      B7-1 and a cell-surface anchored (GPI) form of IL-12 or GM-CSF. Irradiated
      cellular vaccines expressing the combination of adjuvants B7-1 and GPI-IL-12
      completely inhibited tumor formation which was correlative with robust HER-2
      specific CTL activity. However, in a therapeutic setting, both cellular
      vaccination and PD-L1 blockade induced only 10-20% tumor regression when
      administered alone but resulted in 50% tumor regression as a combination therapy.
      This protection was significantly hindered following CD4 or CD8 depletion
      indicating the essential role played by cellular immunity. Collectively, these
      pre-clinical studies provide a strong rationale for further investigation into
      the efficacy of combination therapy with tumor cell vaccines adjuvanted with
      membrane-anchored ISMs along with PD-L1 blockade for the treatment of breast
      cancer. 

PMID- 26308598
TI  - Giant Orbital Hydrocystoma in Children: Case Series and Review of the Literature.
AB  - OBJECTIVE: To describe the clinical features, ancillary diagnostic studies, and
      treatment outcomes in a cohort of pediatric patients with giant orbital
      hydrocystomas. DESIGN: Retrospective case series. PARTICIPANTS: Pediatric
      patients with giant orbital hydrocystomas treated in the practice of one surgeon
      (PDL). METHODS: A retrospective review of the clinical charts of pediatric
      patients with orbital hydrocystoma was performed and diagnostic information
      collected. Results were reviewed and compared with reported clinical data in the
      literature. MAIN OUTCOME MEASURES: Clinical presentation and histopathological
      findings of pediatric orbital hydrocystomas. RESULTS: Three pediatric cases of
      giant orbital hydrocystoma were encountered, each with an unusual feature,
      including deep orbital location, occurrence following trauma, and eccrine
      pathology. CONCLUSION: Giant orbital hydrocystomas may present in the pediatric
      population. Ophthalmologists should be cognizant of this entity when evaluating a
      child with a large, cystic orbital mass.

PMID- 26308599
TI  - Decreased Interferon Alpha/Beta Signature Associated with Human Lung
      Tumorigenesis.
AB  - Accumulating evidence suggests that interferon (IFN) alpha/beta are involved in
      antitumor immunity and cancer immunoediting, but information on the antitumor
      effects of IFN alpha/beta in lung cancer is limited. In our study, we elucidated
      the IFN alpha/beta signature during both human fetal lung development and lung
      tumorigenesis. Our findings indicated gradual upregulation in the IFN alpha/beta
      signature during human fetal lung development. In addition, this signature was
      progressively downregulated in normal human airway epithelial cells from lung
      cancer patients, in immortalized human bronchial epithelial cell lines from later
      passages, in late-stage lung squamous cell carcinoma (LSCC) tissues, and in LSCC
      tissues exhibiting lymph node metastasis. Therefore, from its earliest stages,
      lung tumorigenesis may be associated with a decreased IFN alpha/beta signature.
      This association may provide insight to guide the detection of high-risk lung
      cancer patients. 

PMID- 26308600
TI  - Understanding the pathogenesis of abdominal aortic aneurysms.
AB  - An aortic aneurysm is a dilatation in which the aortic diameter is >=3.0 cm. If
      left untreated, the aortic wall continues to weaken and becomes unable to
      withstand the forces of the luminal blood pressure resulting in progressive
      dilatation and rupture, a catastrophic event associated with a mortality of 50
      80%. Smoking and positive family history are important risk factors for the
      development of abdominal aortic aneurysms (AAA). Several genetic risk factors
      have also been identified. On the histological level, visible hallmarks of AAA
      pathogenesis include inflammation, smooth muscle cell apoptosis, extracellular
      matrix degradation and oxidative stress. We expect that large genetic, genomic,
      epigenetic, proteomic and metabolomic studies will be undertaken by international
      consortia to identify additional risk factors and biomarkers, and to enhance our
      understanding of the pathobiology of AAA. Collaboration between different
      research groups will be important in overcoming the challenges to develop
      pharmacological treatments for AAA. 

PMID- 26308601
TI  - The subcutaneous implantable cardioverter and defibrillator: advantages,
      limitations and future directions.
AB  - The totally subcutaneous implantable cardioverter and defibrillator (S-ICD)
      represents the most innovative development in implantable cardioverter and
      defibrillator therapy in the last 15 years. Its development arose out of concern
      for the long-term complications of transvenous devices. Clinical trials have
      shown that it is a safe and effective device for patients at risk of sudden
      cardiac death. The lack of transvenous and intracardiac components makes it an
      attractive choice for young patients, those with limited vascular access and
      increased infectious risk. Despite these advantages, the current S-ICD system has
      limitations, including the inability to deliver cardiac pacing. Future
      programming and technologic advancements have the opportunity to dramatically
      improve the efficacy and broaden the patient population treated with the S-ICD. 

PMID- 26308603
TI  - A focus on the prognosis and management of ischemic heart disease in patients
      without evidence of obstructive coronary artery disease.
AB  - Ischemic heart disease without evidence of obstructive coronary artery disease is
      a common phenotype comprising different coronary syndromes with either stable or
      unstable clinical presentation. In this context, the clinical outcome and
      management appear extremely variable, due to different etiologies. Of note,
      coronary microvascular dysfunction is the pathogenetic mechanism linking
      different clinical scenarios in most of the cases. Hence, in this article, we aim
      to provide a systematic approach of reviewing the prognosis and management of
      angina or myocardial infarction without evidence of obstructive coronary artery
      disease. Moreover, we will propose a new scheme of classification by
      distinguishing between angina with normal coronary artery and myocardial
      infarction with normal coronary artery in order to facilitate clinicians to
      perform a proper management workflow. 

PMID- 26308602
TI  - Imaging of prehospital stroke therapeutics.
AB  - Despite significant quality improvement efforts to streamline in-hospital acute
      stroke care in the conventional model, there remain inherent layers of treatment
      delays, which could be eliminated with prehospital diagnostics and therapeutics
      administered in a mobile stroke unit. Early diagnosis using telestroke and
      neuroimaging while in the ambulance may enable targeted routing to hospitals with
      specialized care, which will likely improve patient outcomes. Key clinical trials
      in telestroke, mobile stroke units with prehospital neuroimaging capability,
      prehospital ultrasound and co-administration of various classes of
      neuroprotectives, antiplatelets and antithrombin agents with intravenous
      thrombolysis are discussed in this article. 

PMID- 26308604
TI  - Admissions to detoxification after treatment: Does engagement make a difference?
AB  - BACKGROUND: Treatment engagement is a well-established performance measure for
      the treatment of substance use disorders. This study examined whether outpatient
      treatment engagement is associated with a reduced likelihood of subsequent
      detoxification admissions. METHODS: This study used administrative data on
      treatment services received by clients in specialty treatment facilities licensed
      in Massachusetts. The sample consisted of 11,591 adult clients who began an
      outpatient treatment episode in 2006. Treatment engagement was defined as receipt
      of at least 1 treatment service within 14 days of beginning a new outpatient
      treatment episode and receipt of at least 2 additional treatment services in the
      next 30 days. The outcome was a subsequent detoxification admission. Multilevel
      survival models examined the relationship between engagement and outcomes, with
      time to detoxification admission as the dependent variable censored at 365 days.
      RESULTS: Only 35% of clients met the outpatient engagement criteria, and 15% of
      clients had a detoxification admission within a year after beginning their
      outpatient treatment episode. Controlling for client demographics, insurance
      type, and substance use severity, clients who met the engagement criteria had a
      lower hazard of having a detoxification admission during the year following the
      index outpatient visit than those who did not engage (hazard ratio = 0.87, P <
      .01). CONCLUSIONS: Treatment engagement is a useful measure for monitoring
      quality of care. The findings from this study could help inform providers and
      policy makers on ways to target care and reduce the likelihood of more intensive
      services.

PMID- 26308605
TI  - Patterns of Disruptive Feeding Behaviors in Infants With Neonatal Abstinence
      Syndrome.
AB  - BACKGROUND: Severe irritability in infants with neonatal abstinence syndrome
      often impacts their ability to feed successfully, which challenges a mother's
      ability to demonstrate this most basic parenting skill. There is little empiric
      evidence to guide recommendations for practice in this population. PURPOSE:
      Describe the infant behaviors that disrupt feeding in infants with neonatal
      abstinence syndrome. METHODS: A mixed-method approach was used to describe
      digitally recorded infant feeding behaviors. Qualitative methodology was first
      used to identify categories of behaviors during the feeding. The categories were
      used as a coding scheme to identify the temporal sequence, duration, and
      frequency of behaviors observed during a feeding. RESULTS: The behavior
      categories that disrupted feeding were identified as fussing, resting, crying,
      and sleeping/sedated. Infants spent almost twice as much time in fussing as in
      feeding. The majority of the infants were fussing between 1 and 11 minutes during
      the feeding, and fussing disrupted feeding in every subject at least once.
      Feeding behavior occurred only 24% of the time, while fussing and crying occurred
      51%. Fussing was the primary transitional behavior from one category to another.
      Infants who did not complete their feeding had nearly twice the mean number of
      fussing episodes as those who completed their feeding. IMPLICATIONS FOR PRACTICE:
      Fussing is a transitional state and appears to provide an opportunity to test
      interventions that help the mothers re-engage their infants in feeding. The
      frequency of the behavioral transitions provides a measure of irritability that
      has not been previously described in this population. IMPLICATIONS FOR RESEARCH:
      Additional study is needed to evaluate the impact and contributions of maternal
      behaviors and external variables on infant behavioral transition.

PMID- 26308606
TI  - Towards a greater appreciation of manual therapy challenges in the thoracic
      spine.

PMID- 26308607
TI  - Bleomycin-Induced Pneumonitis in the Treatment of Ovarian Sex Cord-Stromal
      Tumors: A Systematic Review and Meta-analysis.
AB  - OBJECTIVE: Adult ovarian sex cord-stromal tumors (SCSTs) are a rare histological
      subtype of ovarian cancer associated with a favorable prognosis. Bleomycin
      containing regimens are standards of care, although pneumonitis may cause
      potentially fatal dose-limiting toxicity. We aimed to evaluate the safety of
      bleomycin in SCST treatment. METHODS: We performed a systematic literature review
      of all studies of bleomycin therapy for SCSTs that were referenced in MEDLINE
      (PubMed), EMBASE, and Cochrane Central Register of Controlled Trials and
      published from 1986 to 2014. RESULTS: Eight studies totaling 221 patients were
      included. Rates of pneumonitis (7.7%; 95% confidence interval, 4.2-11.2) and
      mortality (1.8%; 95% confidence interval, 0.1-3.6) related to bleomycin were
      significant. However, these results were very similar to those reported for men
      who were treated with bleomycin for a male germ cell tumor, suggesting that women
      with ovarian SCSTs are not particularly vulnerable to bleomycin lung toxicity.
      The main risk factors of bleomycin-induced pneumonitis are high cumulative
      bleomycin dose (>400 U or mg), age older than 40 years, and impaired renal
      function. Whether granulocyte colony-stimulating factor is a risk factor remains
      controversial. CONCLUSIONS: Bleomycin-induced pneumonitis frequently occurs in
      patients with SCSTs and lacks effective treatment. Prevention lies in limiting
      cumulative bleomycin dose, monitoring pulmonary function during treatment,
      discontinuing bleomycin at the onset of pulmonary symptoms or if pulmonary
      function is impaired, and avoiding bleomycin in older patients.

PMID- 26308608
TI  - Impact of an Institutional Guideline on the Care of Neonates at Risk for Herpes
      Simplex Virus in the Emergency Department.
AB  - BACKGROUND AND OBJECTIVES: Herpes simplex virus (HSV) is rare in neonates but
      carries significant morbidity and mortality in that group. Emergency department
      (ED) clinicians have little guidance to decide when to test for HSV and give
      acyclovir. We created an institutional guideline to provide guidance in patients
      younger than 6 weeks. Our objective was to evaluate whether guideline
      implementation affected the ED's decision to test for HSV, and ED use of HSV
      polymerase chain reactions (PCRs) and acyclovir. METHODS: We reviewed charts for
      patients 1 year before implementation and 1 year after implementation of our
      guideline. Inclusion criteria were younger than 60 days, admitted through the ED,
      symptom onset younger than 6 weeks, and any one of the following criteria: (1) ED
      blood culture obtained, (2) ED or inpatient HSV PCR obtained, and (3) ED or
      inpatient acyclovir treatment. Premature patients and transfer patients were
      excluded. We compared whether the decision to initiate HSV testing, ED use of HSV
      PCRs, serum alanine aminotransferase, and acyclovir use changed post-guideline
      implementation. RESULTS: We reviewed 173 charts pre-implementation and 129 post
      implementation. We found a significant decrease in ED testing for HSV among
      patients who did not meet guideline criteria (P < 0.01). We saw an improvement in
      the use of alanine aminotransferase among patients who met criteria for testing
      (P = 0.02), but no change in the use of HSV PCRs or acyclovir use among tested
      patients. CONCLUSIONS: Guideline implementation reduced HSV evaluations in low
      risk patients, but did not improve test utilization or acyclovir administration
      among those tested. Additional work is needed to improve guideline utilization.

PMID- 26308609
TI  - Point-of-Care Ultrasound for the Detection of Traumatic Intracranial Hemorrhage
      in Infants: A Pilot Study.
AB  - OBJECTIVES: Computed tomography is the criterion standard imaging modality to
      detect intracranial hemorrhage (ICH) in children and infants after closed head
      injury, but its use can be limited by patient instability, need for sedation, and
      risk of ionizing radiation exposure. Cranial ultrasound is used routinely to
      detect intraventricular hemorrhage in neonates. We sought to determine if point
      of-care (POC) cranial ultrasound performed by emergency physicians can detect
      traumatic ICH in infants. METHODS: Infants with ICH diagnosed by computed
      tomography were identified. For every infant with an ICH, 2 controls with
      symptoms and diagnoses unrelated to head trauma were identified. Point-of-care
      cranial ultrasound was performed by an emergency physician on all patients, and
      video clips were recorded. Two ultrasound fellowship-trained emergency
      physicians, blinded to the patients' diagnosis and clinical status, independently
      reviewed the ultrasound clips and determined the presence or absence of ICH.
      RESULTS: Twelve patients were included in the study, 4 with ICH and 8 controls.
      Observer 1 identified ICH with 100% sensitivity (95% confidence interval [CI],
      40%-100%) and 100% specificity (95% CI, 60%-100%). Observer 2 identified ICH with
      50% sensitivity (95% CI, 9%-98%) and 87.5% specificity (95% CI, 47%-99%).
      Agreement between observers was 75%, kappa = 0.4 (P = 0.079; 95% CI, 0-0.95).
      CONCLUSIONS: Traumatic ICH can be identified with POC cranial ultrasound by
      ultrasound fellowship-trained emergency physicians. Although variations between
      observers and wide confidence intervals preclude drawing meaningful conclusions
      about sensitivity and specificity from this sample, these results support the
      need for further investigation into the role of POC cranial ultrasound.

PMID- 26308610
TI  - Pluripotency, Differentiation, and Reprogramming: A Gene Expression Dynamics
      Model with Epigenetic Feedback Regulation.
AB  - Embryonic stem cells exhibit pluripotency: they can differentiate into all types
      of somatic cells. Pluripotent genes such as Oct4 and Nanog are activated in the
      pluripotent state, and their expression decreases during cell differentiation.
      Inversely, expression of differentiation genes such as Gata6 and Gata4 is
      promoted during differentiation. The gene regulatory network controlling the
      expression of these genes has been described, and slower-scale epigenetic
      modifications have been uncovered. Although the differentiation of pluripotent
      stem cells is normally irreversible, reprogramming of cells can be experimentally
      manipulated to regain pluripotency via overexpression of certain genes. Despite
      these experimental advances, the dynamics and mechanisms of differentiation and
      reprogramming are not yet fully understood. Based on recent experimental
      findings, we constructed a simple gene regulatory network including pluripotent
      and differentiation genes, and we demonstrated the existence of pluripotent and
      differentiated states from the resultant dynamical-systems model. Two
      differentiation mechanisms, interaction-induced switching from an expression
      oscillatory state and noise-assisted transition between bistable stationary
      states, were tested in the model. The former was found to be relevant to the
      differentiation process. We also introduced variables representing epigenetic
      modifications, which controlled the threshold for gene expression. By assuming
      positive feedback between expression levels and the epigenetic variables, we
      observed differentiation in expression dynamics. Additionally, with numerical
      reprogramming experiments for differentiated cells, we showed that pluripotency
      was recovered in cells by imposing overexpression of two pluripotent genes and
      external factors to control expression of differentiation genes. Interestingly,
      these factors were consistent with the four Yamanaka factors, Oct4, Sox2, Klf4,
      and Myc, which were necessary for the establishment of induced pluripotent stem
      cells. These results, based on a gene regulatory network and expression dynamics,
      contribute to our wider understanding of pluripotency, differentiation, and
      reprogramming of cells, and they provide a fresh viewpoint on robustness and
      control during development. 

PMID- 26308611
TI  - Transcriptome-wide identification of Camellia sinensis WRKY transcription factors
      in response to temperature stress.
AB  - Tea plant [Camellia sinensis (L.) O. Kuntze] is a leaf-type healthy non-alcoholic
      beverage crop, which has been widely introduced worldwide. Tea is rich in various
      secondary metabolites, which are important for human health. However, varied
      climate and complex geography have posed challenges for tea plant survival. The
      WRKY gene family in plants is a large transcription factor family that is
      involved in biological processes related to stress defenses, development, and
      metabolite synthesis. Therefore, identification and analysis of WRKY family
      transcription factors in tea plant have a profound significance. In the present
      study, 50 putative C. sinensis WRKY proteins (CsWRKYs) with complete WRKY domain
      were identified and divided into three Groups (Group I-III) on the basis of
      phylogenetic analysis results. The distribution of WRKY family transcription
      factors among plantae, fungi, and protozoa showed that the number of WRKY genes
      increased in higher plant, whereas the number of these genes did not correspond
      to the evolutionary relationships of different species. Structural feature and
      annotation analysis results showed that CsWRKY proteins contained WRKYGQK/WRKYGKK
      domains and C2H2/C2HC-type zinc-finger structure: D-X18-R-X1-Y-X2-C-X4-7-C-X23-H
      motif; CsWRKY proteins may be associated with the biological processes of abiotic
      and biotic stresses, tissue development, and hormone and secondary metabolite
      biosynthesis. Temperature stresses suggested that the candidate CsWRKY genes were
      involved in responses to extreme temperatures. The current study established an
      extensive overview of the WRKY family transcription factors in tea plant. This
      study also provided a global survey of CsWRKY transcription factors and a
      foundation of future functional identification and molecular breeding. 

PMID- 26308613
TI  - A Multilevel Regression Model for Geographical Studies in Sets of Non-Adjacent
      Cities.
AB  - In recent years, small-area-based ecological regression analyses have been
      published that study the association between a health outcome and a covariate in
      several cities. These analyses have usually been performed independently for each
      city and have therefore yielded unrelated estimates for the cities considered,
      even though the same process has been studied in all of them. In this study, we
      propose a joint ecological regression model for multiple cities that accounts for
      spatial structure both within and between cities and explore the advantages of
      this model. The proposed model merges both disease mapping and geostatistical
      ideas. Our proposal is compared with two alternatives, one that models the
      association for each city as fixed effects and another that treats them as
      independent and identically distributed random effects. The proposed model allows
      us to estimate the association (and assess its significance) at locations with no
      available data. Our proposal is illustrated by an example of the association
      between unemployment (as a deprivation surrogate) and lung cancer mortality among
      men in 31 Spanish cities. In this example, the associations found were far more
      accurate for the proposed model than those from the fixed effects model. Our main
      conclusion is that ecological regression analyses can be markedly improved by
      performing joint analyses at several locations that share information among them.
      This finding should be taken into consideration in the design of future
      epidemiological studies. 

PMID- 26308612
TI  - Efficacy and Safety of Sorafenib Therapy on Metastatic Renal Cell Carcinoma in
      Korean Patients: Results from a Retrospective Multicenter Study.
AB  - OBJECTIVE: To evaluate the efficacy and safety of sorafenib for Korean patients
      with metastatic renal cell carcinoma (mRCC). METHODS: A total of 177 mRCC
      patients using sorafenib as first- (N = 116), second- (N = 43), and third-line (N
      = 18) therapies were enrolled from 11 Korean centers between 2006 and 2012. The
      patient characteristics, therapy duration, tumor response, disease control rate,
      and tolerability were assessed at baseline and at routine follow-ups, and the
      progression-free survival (PFS) and overall survival (OS) times and rates were
      analyzed. RESULTS: Among all patients, 18 (10.2%) stopped sorafenib treatment for
      a median of 1.7 weeks, including 15 (8.5%) who discontinued the drug, while 40
      (22.6%) and 12 (6.8%) patients required dose reductions and drug interruptions,
      respectively. Severe adverse events (AEs) or poor compliance was observed in 64
      (36.2%) patients, with 118 (7.4%) >=grade 3 AEs. During the treatment, one
      myocardial infarction was observed. The number of >=grade 3 AEs in the first-line
      sorafenib group was 71 (6.8% of the total 1048 AEs). During a median follow-up of
      17.2 months, the radiologically confirmed best objective response rate, disease
      control rate, median PFS, and median OS were 22.0%, 53.0%, 6.4 months (95%
      confidence interval [CI], 5.2-8.9), and 32.6 months (95% CI, 27.3-63.8) for the
      total 177 sorafenib-treated patients, respectively, and 23.2%, 56.0%, 7.4 months
      (95% CI, 5.5-10.5), and not reached yet (95% CI, 1.0-31.1) for the first-line
      sorafenib group, respectively. CONCLUSIONS: Sorafenib produced tolerable safety,
      with a >=grade 3 AE rate of 7.4% and an acceptable disease control rate (53.0%)
      in Korean mRCC patients.

PMID- 26308614
TI  - Stem Cells in Myometrial Physiology.
AB  - Normal adult tissues contain a small subset of tissue-specific stem cells. These
      stem cells are capable of self-renewing as well as generating daughter cells that
      are destined to completely differentiate and thereby support tissue remodeling
      and repair. The human uterus is an example of how such cell populations support
      the function of an organ. The uterus primarily consists of endometrium and
      myometrium, and these tissues rapidly enlarge to support the developing fetus
      during pregnancy. Uterine enlargement and remodeling can occur more than a dozen
      times during a woman's reproductive life. The expansion of the gravid uterus is
      achieved mainly through myometrial hyperplasia and hypertrophy, and these
      processes suggest an important role for stem/progenitor cell systems. Recently,
      stem/progenitor cells in the myometrium have been identified and their properties
      characterized. Here, we discuss some of the properties of myometrial
      stem/progenitor cells. We also suggest a new model of myometrial physiology and
      how stem cell systems might contribute to pregnancy-associated uterine
      remodeling. 

PMID- 26308615
TI  - Smart-Phone Based Magnetic Levitation for Measuring Densities.
AB  - Magnetic levitation, which uses a magnetic field to suspend objects in a fluid,
      is a powerful and versatile technology. We develop a compact magnetic levitation
      platform compatible with a smart-phone to separate micro-objects and estimate the
      density of the sample based on its levitation height. A 3D printed attachment is
      mechanically installed over the existing camera unit of a smart-phone. Micro
      objects, which may be either spherical or irregular in shape, are suspended in a
      paramagnetic medium and loaded in a microcapillary tube which is then inserted
      between two permanent magnets. The micro-objects are levitated and confined in
      the microcapillary at an equilibrium height dependent on their volumetric mass
      densities (causing a buoyancy force toward the edge of the microcapillary) and
      magnetic susceptibilities (causing a magnetic force toward the center of the
      microcapillary) relative to the suspending medium. The smart-phone camera
      captures magnified images of the levitating micro-objects through an additional
      lens positioned between the sample and the camera lens cover. A custom-developed
      Android application then analyzes these images to determine the levitation height
      and estimate the density. Using this platform, we were able to separate
      microspheres with varying densities and calibrate their levitation heights to
      known densities to develop a technique for precise and accurate density
      estimation. We have also characterized the magnetic field, the optical imaging
      capabilities, and the thermal state over time of this platform. 

PMID- 26308616
TI  - Vasomotor Reaction to Cyclooxygenase-1-Mediated Prostacyclin Synthesis in Carotid
      Arteries from Two-Kidney-One-Clip Hypertensive Mice.
AB  - This study tested the hypothesis that in hypertensive arteries cyclooxygenase-1
      (COX-1) remains as a major form, mediating prostacyclin (prostaglandin I2; PGI2)
      synthesis that may evoke a vasoconstrictor response in the presence of functional
      vasodilator PGI2 (IP) receptors. Two-kidney-one-clip (2K1C) hypertension was
      induced in wild-type (WT) mice and/or those with COX-1 deficiency (COX-1-/-).
      Carotid arteries were isolated for analyses 4 weeks after. Results showed that as
      in normotensive mice, the muscarinic receptor agonist ACh evoked a production of
      the PGI2 metabolite 6-keto-PGF1alpha and an endothelium-dependent vasoconstrictor
      response; both of them were abolished by COX-1 inhibition. At the same time,
      PGI2, which evokes contraction of hypertensive vessels, caused relaxation after
      thromboxane-prostanoid (TP) receptor antagonism that abolished the contraction
      evoked by ACh. Antagonizing IP receptors enhanced the contraction to the COX
      substrate arachidonic acid (AA). Also, COX-1-/- mice was noted to develop
      hypertension; however, their increase of blood pressure and/or heart mass was not
      to a level achieved with WT mice. In addition, we found that either the
      contraction in response to ACh or that evoked by AA was abolished in COX-1-/-
      hypertensive mice. These results demonstrate that as in normotensive conditions,
      COX-1 is a major contributor of PGI2 synthesis in 2K1C hypertensive carotid
      arteries, which leads to a vasoconstrictor response resulting from opposing
      dilator and vasoconstrictor activities of IP and TP receptors, respectively.
      Also, our data suggest that COX-1-/- attenuates the development of 2K1C
      hypertension in mice, reflecting a net adverse role yielded from all COX-1
      mediated activities under the pathological condition. 

PMID- 26308617
TI  - A New Imaging Platform for Visualizing Biological Effects of Non-Invasive
      Radiofrequency Electric-Field Cancer Hyperthermia.
AB  - Herein, we present a novel imaging platform to study the biological effects of
      non-invasive radiofrequency (RF) electric field cancer hyperthermia. This system
      allows for real-time in vivo intravital microscopy (IVM) imaging of
      radiofrequency-induced biological alterations such as changes in vessel structure
      and drug perfusion. Our results indicate that the IVM system is able to handle
      exposure to high-power electric-fields without inducing significant hardware
      damage or imaging artifacts. Furthermore, short durations of low-power (< 200 W)
      radiofrequency exposure increased transport and perfusion of fluorescent tracers
      into the tumors at temperatures below 41 degrees C. Vessel deformations and blood
      coagulation were seen for tumor temperatures around 44 degrees C. These results
      highlight the use of our integrated IVM-RF imaging platform as a powerful new
      tool to visualize the dynamics and interplay between radiofrequency energy and
      biological tissues, organs, and tumors. 

PMID- 26308618
TI  - Hepatic Shunting of Eggs and Pulmonary Vascular Remodeling in Bmpr2(+/-) Mice
      with Schistosomiasis.
AB  - RATIONALE: Schistosomiasis is a major cause of pulmonary arterial hypertension
      (PAH). Mutations in the bone morphogenetic protein type-II receptor (BMPR-II) are
      the commonest genetic cause of PAH. OBJECTIVES: To determine whether Bmpr2(+/-)
      mice are more susceptible to schistosomiasis-induced pulmonary vascular
      remodeling. METHODS: Wild-type (WT) and Bmpr2(+/-) mice were infected
      percutaneously with Schistosoma mansoni. At 17 weeks postinfection, right
      ventricular systolic pressure and liver and lung egg counts were measured. Serum,
      lung and liver cytokine, pulmonary vascular remodeling, and liver histology were
      assessed. MEASUREMENTS AND MAIN RESULTS: By 17 weeks postinfection, there was a
      significant increase in pulmonary vascular remodeling in infected mice. This was
      greater in Bmpr2(+/-) mice and was associated with an increase in egg deposition
      and cytokine expression, which induced pulmonary arterial smooth muscle cell
      proliferation, in the lungs of these mice. Interestingly, Bmpr2(+/-) mice
      demonstrated dilatation of the hepatic central vein at baseline and
      postinfection, compared with WT. Bmpr2(+/-) mice also showed significant
      dilatation of the liver sinusoids and an increase in inflammatory cells
      surrounding the central hepatic vein, compared with WT. This is consistent with
      an increase in the transhepatic passage of eggs. CONCLUSIONS: This study has
      shown that levels of BMPR-II expression modify the pulmonary vascular response to
      chronic schistosomiasis. The likely mechanism involves the increased passage of
      eggs to the lungs, caused by altered diameter of the hepatic veins and sinusoids
      in Bmpr2(+/-) mice. Genetically determined differences in the remodeling of
      hepatic vessels may represent a new risk factor for PAH associated with
      schistosomiasis.

PMID- 26308619
TI  - Social Behavioral Deficits Coincide with the Onset of Seizure Susceptibility in
      Mice Lacking Serotonin Receptor 2c.
AB  - The development of social behavior is strongly influenced by the serotonin
      system. Serotonin 2c receptor (5-HT2cR) is particularly interesting in this
      context considering that pharmacological modulation of 5-HT2cR activity alters
      social interaction in adult rodents. However, the role of 5-HT2cR in the
      development of social behavior is unexplored. Here we address this using Htr2c
      knockout mice, which lack 5-HT2cR. We found that these animals exhibit social
      behavior deficits as adults but not as juveniles. Moreover, we found that the age
      of onset of these deficits displays similar timing as the onset of susceptibility
      to spontaneous death and audiogenic-seizures, consistent with the hypothesis that
      imbalanced excitation and inhibition (E/I) may contribute to social behavioral
      deficits. Given that autism spectrum disorder (ASD) features social behavioral
      deficits and is often co-morbid with epilepsy, and given that 5-HT2cR physically
      interacts with Pten, we tested whether a second site mutation in the ASD risk
      gene Pten can modify these phenotypes. The age of spontaneous death is
      accelerated in mice double mutant for Pten and Htr2c relative to single mutants.
      We hypothesized that pharmacological antagonism of 5-HT2cR activity in adult
      animals, which does not cause seizures, might modify social behavioral deficits
      in Pten haploinsufficient mice. SB 242084, a 5-HT2cR selective antagonist, can
      reverse the social behavior deficits observed in Pten haploinsufficient mice.
      Together, these results elucidate a role of 5-HT2cR in the modulation of social
      behavior and seizure susceptibility in the context of normal development and Pten
      haploinsufficiency. 

PMID- 26308620
TI  - Diversity of Marine-Derived Fungal Cultures Exposed by DNA Barcodes: The
      Algorithm Matters.
AB  - Marine fungi are an understudied group of eukaryotic microorganisms characterized
      by unresolved genealogies and unstable classification. Whereas DNA barcoding via
      the nuclear ribosomal internal transcribed spacer (ITS) provides a robust and
      rapid tool for fungal species delineation, accurate classification of fungi is
      often arduous given the large number of partial or unknown barcodes and
      misidentified isolates deposited in public databases. This situation is
      perpetuated by a paucity of cultivable fungal strains available for phylogenetic
      research linked to these data sets. We analyze ITS barcodes produced from a
      subsample (290) of 1781 cultured isolates of marine-derived fungi in the
      Bioresources Library located at the Australian Institute of Marine Science
      (AIMS). Our analysis revealed high levels of under-explored fungal diversity. The
      majority of isolates were ascomycetes including representatives of the subclasses
      Eurotiomycetidae, Hypocreomycetidae, Sordariomycetidae, Pleosporomycetidae,
      Dothideomycetidae, Xylariomycetidae and Saccharomycetidae. The phylum
      Basidiomycota was represented by isolates affiliated with the genera Tritirachium
      and Tilletiopsis. BLAST searches revealed 26 unknown OTUs and 50 isolates
      corresponding to previously uncultured, unidentified fungal clones. This study
      makes a significant addition to the availability of barcoded, culturable marine
      derived fungi for detailed future genomic and physiological studies. We also
      demonstrate the influence of commonly used alignment algorithms and genetic
      distance measures on the accuracy and comparability of estimating Operational
      Taxonomic Units (OTUs) by the automatic barcode gap finder (ABGD) method. Large
      scale biodiversity screening programs that combine datasets using algorithmic OTU
      delineation pipelines need to ensure compatible algorithms have been used because
      the algorithm matters. 

PMID- 26308622
TI  - A scanning tunneling microscope break junction method with continuous bias
      modulation.
AB  - Single molecule conductance measurements on 1,8-octanedithiol were performed
      using the scanning tunneling microscope break junction method with an externally
      controlled modulation of the bias voltage. Application of an AC voltage is shown
      to improve the signal to noise ratio of low current (low conductance)
      measurements as compared to the DC bias method. The experimental results show
      that the current response of the molecule(s) trapped in the junction and the
      solvent media to the bias modulation can be qualitatively different. A model RC
      circuit which accommodates both the molecule and the solvent is proposed to
      analyze the data and extract a conductance for the molecule. 

PMID- 26308621
TI  - Novel Analysis Software for Detecting and Classifying Ca2+ Transient
      Abnormalities in Stem Cell-Derived Cardiomyocytes.
AB  - Comprehensive functioning of Ca2+ cycling is crucial for excitation-contraction
      coupling of cardiomyocytes (CMs). Abnormal Ca2+ cycling is linked to
      arrhythmogenesis, which is associated with cardiac disorders and heart failure.
      Accordingly, we have generated spontaneously beating CMs from induced pluripotent
      stem cells (iPSC) derived from patients with catecholaminergic polymorphic
      ventricular tachycardia (CPVT), which is an inherited and severe cardiac disease.
      Ca2+ cycling studies have revealed substantial abnormalities in these CMs. Ca2+
      transient analysis performed manually lacks accepted analysis criteria, and has
      both low throughput and high variability. To overcome these issues, we have
      developed a software tool, AnomalyExplorer based on interactive visualization, to
      assist in the classification of Ca2+ transient patterns detected in CMs. Here, we
      demonstrate the usability and capability of the software, and we also compare the
      analysis efficiency to manual analysis. We show that AnomalyExplorer is suitable
      for detecting normal and abnormal Ca2+ transients; furthermore, this method
      provides more defined and consistent information regarding the Ca2+ abnormality
      patterns and cell line specific differences when compared to manual analysis.
      This tool will facilitate and speed up the analysis of CM Ca2+ transients, making
      it both more accurate and user-independent. AnomalyExplorer can be exploited in
      Ca2+ cycling analysis to study basic disease pathology and the effects of
      different drugs. 

PMID- 26308623
TI  - The Prostaglandin E2 Receptor EP4 Regulates Obesity-Related Inflammation and
      Insulin Sensitivity.
AB  - With increasing body weight, macrophages accumulate in adipose tissue. There,
      activated macrophages secrete numerous proinflammatory cytokines and chemokines,
      giving rise to chronic inflammation and insulin resistance. Prostaglandin E2
      suppresses macrophage activation via EP4; however, the role of EP4 signaling in
      insulin resistance and type 2 diabetes mellitus remains unknown. In this study,
      we treated db/db mice with an EP4-selective agonist, ONO-AE1-329, for 4 weeks to
      explore the role of EP4 signaling in obesity-related inflammation in vivo.
      Administration of the EP4 agonist did not affect body weight gain or food intake;
      however, in the EP4 agonist-treated group, glucose tolerance and insulin
      resistance were significantly improved over that of the vehicle-treated group.
      Additionally, administration of the EP4 agonist inhibited the accumulation of
      F4/80-positive macrophages and the formation of crown-like structures in white
      adipose tissue, and the adipocytes were significantly smaller. The treatment of
      the EP4 agonist increased the number of anti-inflammatory M2 macrophages, and in
      the stromal vascular fraction of white adipose tissue, which includes
      macrophages, it markedly decreased the levels of proinflammatory cytokines and
      chemokines. Further, EP4 activation increased the expression of adiponectin and
      peroxidase proliferator-activated receptors in white adipose tissue. Next, we
      examined in vitro M1/M2 polarization assay to investigate the impact of EP4
      signaling on determining the functional phenotypes of macrophages. Treatment with
      EP4 agonist enhanced M2 polarization in wild-type peritoneal macrophages, whereas
      EP4-deficient macrophages were less susceptible to M2 polarization. Notably,
      antagonizing peroxidase proliferator-activated receptor delta activity suppressed
      EP4 signaling-mediated shift toward M2 macrophage polarization. Thus, our results
      demonstrate that EP4 signaling plays a critical role in obesity-related adipose
      tissue inflammation and insulin resistance by regulating macrophage recruitment
      and polarization. The activation of EP4 signaling holds promise for treating
      obesity and type 2 diabetes mellitus. 

PMID- 26308626
TI  - The conjugates of ferrocene-1,1'-diamine and amino acids. A novel synthetic
      approach and conformational analysis.
AB  - A novel synthetic approach toward a poorly explored bioorganometallic consisting
      of ferrocene-1,1'-diamine bearing structurally and chirally diverse amino acid
      sequences is reported. Until now, ferrocene-1,1'-diamine was suitable for
      accommodating only identical amino acid sequences at its N-termini, leading to
      the symmetrically disubstituted homochiral products stabilized through a 14
      membered intramolecular hydrogen-bonded ring as is seen in antiparallel beta
      sheet peptides. The key step of the novel synthetic pathway is the transformation
      of Ac-Ala-NH-Fn-COOH (5) (Fn = 1,1'-ferrocenylene) to orthogonally protected Ac
      Ala-NH-Fn-NHBoc (7). The spectroscopic analysis (IR, NMR, CD) of the novel
      compounds, corroborated with DFT studies, suggests the interesting feature of the
      ferrocene-1,1'-diamine scaffold. The same hydrogen-bonding pattern, i.e. a 14
      membered hydrogen-bonded ring, was determined both in solution and in the solid
      state, thus making them promising, yet simple scaffolds capable of mimicking beta
      sheet peptides. In vitro screening of potential anticancer activity in Hep G2
      human liver carcinoma cells and Hs 578 T human breast cancer cells revealed a
      cytotoxic pattern for novel compounds (150-500 MUM) with significantly decreased
      cell proliferation.

PMID- 26308624
TI  - Temporal Gene Expression of the Cyanobacterium Arthrospira in Response to Gamma
      Rays.
AB  - The edible cyanobacterium Arthrospira is resistant to ionising radiation. The
      cellular mechanisms underlying this radiation resistance are, however, still
      largely unknown. Therefore, additional molecular analysis was performed to
      investigate how these cells can escape from, protect against, or repair the
      radiation damage. Arthrospira cells were shortly exposed to different doses of
      60Co gamma rays and the dynamic response was investigated by monitoring its gene
      expression and cell physiology at different time points after irradiation. The
      results revealed a fast switch from an active growth state to a kind of 'survival
      modus' during which the cells put photosynthesis, carbon and nitrogen
      assimilation on hold and activate pathways for cellular protection,
      detoxification, and repair. The higher the radiation dose, the more pronounced
      this global emergency response is expressed. Genes repressed during early
      response, suggested a reduction of photosystem II and I activity and reduced
      tricarboxylic acid (TCA) and Calvin-Benson-Bassham (CBB) cycles, combined with an
      activation of the pentose phosphate pathway (PPP). For reactive oxygen species
      detoxification and restoration of the redox balance in Arthrospira cells, the
      results suggested a powerful contribution of the antioxidant molecule
      glutathione. The repair mechanisms of Arthrospira cells that were immediately
      switched on, involve mainly proteases for damaged protein removal, single strand
      DNA repair and restriction modification systems, while recA was not induced.
      Additionally, the exposed cells showed significant increased expression of arh
      genes, coding for a novel group of protein of unknown function, also seen in our
      previous irradiation studies. This observation confirms our hypothesis that arh
      genes are key elements in radiation resistance of Arthrospira, requiring further
      investigation. This study provides new insights into phasic response and the
      cellular pathways involved in the radiation resistance of microbial cells, in
      particularly for photosynthetic organisms as the cyanobacterium Arthrospira. 

PMID- 26308629
TI  - Prognostic Value of the Amount of Bleeding After Aneurysmal Subarachnoid
      Hemorrhage: A Quantitative Volumetric Study.
AB  - BACKGROUND: Quantitative estimation of the hemorrhage volume associated with
      aneurysm rupture is a new tool of assessing prognosis. OBJECTIVE: To determine
      the prognostic value of the quantitative estimation of the amount of bleeding
      after aneurysmal subarachnoid hemorrhage, as well the relative importance of this
      factor related to other prognostic indicators, and to establish a possible cut
      off value of volume of bleeding related to poor outcome. METHODS: A prospective
      cohort of 206 patients consecutively admitted with the diagnosis of aneurysmal
      subarachnoid hemorrhage to Hospital 12 de Octubre were included in the study.
      Subarachnoid, intraventricular, intracerebral, and total bleeding volumes were
      calculated using analytic software. For assessing factors related to prognosis,
      univariate and multivariate analysis (logistic regression) were performed. The
      relative importance of factors in determining prognosis was established by
      calculating their proportion of explained variation. Maximum Youden index was
      calculated to determine the optimal cut point for subarachnoid and total bleeding
      volume. RESULTS: Variables independently related to prognosis were clinical grade
      at admission, age, and the different bleeding volumes. The proportion of variance
      explained is higher for subarachnoid bleeding. The optimal cut point related to
      poor prognosis is a volume of 20 mL both for subarachnoid and total bleeding.
      CONCLUSION: Volumetric measurement of subarachnoid or total bleeding volume are
      both independent prognostic factors in patients with aneurysmal subarachnoid
      hemorrhage. A volume of more than 20 mL of blood in the initial noncontrast
      computed tomography is related to a clear increase in poor outcome risk.
      ABBREVIATION: : aSAH, aneurysmal subarachnoid hemorrhage.

PMID- 26308630
TI  - What is the Surgical Benefit of Utilizing 5-Aminolevulinic Acid for Fluorescence
      Guided Surgery of Malignant Gliomas?
AB  - The current neurosurgical goal for patients with malignant gliomas is maximal
      safe resection of the contrast-enhancing tumor. However, a complete resection of
      the contrast-enhancing tumor is achieved only in a minority of patients. One
      reason for this limitation is the difficulty in distinguishing viable tumor from
      normal adjacent brain during surgery at the tumor margin using conventional white
      light microscopy. To overcome this limitation, fluorescence-guided surgery (FGS)
      using 5-aminolevulinic acid (5-ALA) has been introduced in the treatment of
      malignant gliomas. FGS permits the intraoperative visualization of malignant
      glioma tissue and supports the neurosurgeon with real-time guidance for
      differentiating tumor from normal brain that is independent of neuronavigation
      and brain shift. Tissue fluorescence after oral administration of 5-ALA is
      associated with unprecedented high sensitivity, specificity, and positive
      predictive values for identifying malignant glioma tumor tissue. 5-ALA-induced
      tumor fluorescence in diffusely infiltrating gliomas with non-significant
      magnetic resonance imaging contrast-enhancement permits intraoperative
      identification of anaplastic foci and establishment of an accurate
      histopathological diagnosis for proper adjuvant treatment. 5-ALA FGS has enabled
      surgeons to achieve a significantly higher rate of complete resections of
      malignant gliomas in comparison with conventional white-light resections.
      Consequently, 5-ALA FGS has become an indispensable surgical technique and
      standard of care at many neurosurgical departments around the world. We conducted
      an extensive literature review concerning the surgical benefit of using 5-ALA for
      FGS of malignant gliomas. According to the literature, there are a number of
      reasons for the neurosurgeon to perform 5-ALA FGS, which will be discussed in
      detail in the current review.

PMID- 26308632
TI  - Chiari Severity Index: A Novel Grading System Intended for Preoperative
      Counseling.

PMID- 26308631
TI  - Contralateral Approach to Bilateral Middle Cerebral Artery Aneurysms: Comparative
      Study, Angiographic Analysis, and Surgical Results.
AB  - BACKGROUND: Bilateral aneurysms located between the 2 middle cerebral artery
      (MCA) bifurcations may be approachable through a single unilateral approach.
      OBJECTIVE: To identify anatomic parameters based on imaging that would favor a
      contralateral approach. METHODS: From January 1998 to December 2013, we
      retrospectively identified 173 patients with bilateral intracranial aneurysms.
      Fifty-one patients had bilateral MCA aneurysms. A total of 38 patients underwent
      a single craniotomy with a contralateral microsurgical approach (group 1 or
      contralateral group) and 13 patients underwent bilateral craniotomies (group 2 or
      bilateral group). For both groups, we analyzed aneurysm characteristics,
      morphology, size, projections, and distance to the contralateral corridor, as
      well as surgical time, outcome, and postoperative complications. RESULTS: All
      aneurysms approached contralaterally were unruptured and without wall
      calcifications. Of the contralaterally approached aneurysms, 97% were smaller
      than 14 mm. The median length of the contralateral A1 was 13.2 mm (range: 6-19.8
      mm) and the median length of the contralateral M1 was 14.2 mm (range: 4.6-21 mm).
      The contralateral group had a good postoperative outcome (modified Rankin Scale 0
      3) in 80% of ruptured cases and 86% of unruptured cases. The median surgical time
      was 120 minutes (range: 75-255 minutes), 43% shorter than the bilateral group.
      CONCLUSION: The contralateral approach for bilateral MCA aneurysms in selected
      patients is feasible in experienced hands, with acceptable morbidity and
      mortality. The contralateral approach requires a meticulous preoperative analysis
      of the characteristics of the aneurysms to be clipped and of the anatomic
      constraints of the microsurgical operative corridor. ABBREVIATIONS: A1, anterior
      cerebral artery proximal segmentbMCA, bilateral middle cerebral arteryCTA,
      computed tomographic angiographyHH, Hunt-Hess scaleIA, intracranial aneurysmsICA,
      internal carotid arteryICAbif, internal carotid artery bifurcationMCA, middle
      cerebral arteryM1, middle cerebral artery proximal segmentmRS, modified Rankin
      ScaleSAH, subarachnoid hemorrhage.

PMID- 26308633
TI  - Effect of Carotid Revascularization Endarterectomy Versus Stenting Trial Results
      on the Performance of Carotid Artery Stent Placement and Carotid Endarterectomy
      in the United States.
AB  - BACKGROUND: CREST (Carotid Revascularization Endarterectomy Versus Stenting
      Trial) results, published in 2010, showed no difference in the rates of composite
      outcome (stroke, myocardial infarction, or death) between carotid artery stent
      placement (CAS) and carotid endarterectomy (CEA). OBJECTIVE: To identify any
      changes in use and outcomes of CAS and CEA subsequent to the CREST results.
      METHODS: We estimated the frequency of CAS and CEA procedures in the years 2009
      (pre-CREST period) and 2011 (post-CREST period), using data from the National
      Inpatient Sample (NIS). Demographic and clinical characteristics and in-hospital
      outcomes of pre- and post-CREST CAS-treated and post-CREST CEA-treated patients
      were compared with pre-CREST CEA-treated patients. RESULTS: A total of 225,191
      patients underwent CEA or CAS in the pre- and post-CREST periods. The frequency
      of CAS among carotid revascularization procedures did not change after
      publication of the CREST results (12.3% vs. 12.7%, P = .9). In the pre-CREST
      period, the CAS group (compared with the CEA group) had higher rates of
      congestive heart failure (P < .001), coronary artery disease (P < .001), and
      renal failure (P < .001). The post-CREST CAS group had a higher frequency of
      atrial fibrillation (P = .003), congestive heart failure (P < .0001), coronary
      artery disease (P < .0001), and renal failure (P = .0001). Discharge with
      moderate to severe disability (P < .0001) and postprocedure neurological
      complications (P = .005) were more frequently reported in the post-CREST CAS
      group. After adjusting for age, sex, and risk factors, the odds ratio (OR) for
      moderate to severe disability was 1.0 (95% confidence interval [CI]: 0.8-1.2) in
      the pre-CREST CAS group and 1.4 (95% CI: 1.1-1.7) in the post-CREST CAS group
      compared with the reference group. The adjusted OR for neurological complications
      in the pre-CREST CAS group was 1.6 (95% CI: 1.2-2.1, P = .002), and 1.5 (95% CI:
      1.1-2.0, P = .01) in the post-CREST CAS group. CONCLUSION: The frequency of CAS
      and CEA for carotid artery stenosis has not changed after publication of the
      CREST. The demographics, pretreatment comorbidity profile, and in-hospital
      complication rates remained unchanged during the 2 time periods.

PMID- 26308634
TI  - The Neurological Compromised Spine Due to Ewing Sarcoma. What First: Surgery or
      Chemotherapy? Therapy, Survival, and Neurological Outcome of 15 Cases With
      Primary Ewing Sarcoma of the Vertebral Column.
AB  - BACKGROUND: The vertebral column is an infrequent site of primary involvement in
      Ewing sarcoma. Yet when Ewing sarcoma is found in the spine, the urge for
      decompression is high because of the often symptomatic compression of neural
      structures. It is unclear in alleviating a neurological deficit whether
      chemotherapy is preferred over decompressive laminectomy. OBJECTIVE: To
      underline, in this case series, the efficiency of initial chemotherapy before
      upfront surgery in the setting of high-grade spinal cord or cauda equina
      compression of primary Ewing sarcoma. METHODS: Fifteen patients with Ewing
      sarcoma primarily located in the spine were treated at our institution between
      1983 and 2015. Localization, neurological deficit expressed as Frankel grade, and
      outcome expressed as Rankin scale before and after initial chemotherapy, the
      recurrence rate, and overall survival were evaluated. The multidisciplinary
      approach of 1 case will be discussed in detail. RESULTS: Nine patients (60%) were
      female. The age at presentation was 15.0 +/- 5.5 years (range: 0.9-22.8 years).
      Ten patients (67%) were initially treated with chemotherapy, and 1 patient (7%)
      was treated primarily with radiotherapy followed by chemotherapy. The remaining 4
      patients (27%) were initially treated with decompressive surgery. All patients
      treated primarily nonsurgically improved neurologically at follow-up, showing the
      importance of chemotherapy as an effective initial treatment option. CONCLUSION:
      Adequate and quick decompression of neural structures with similar results can be
      achieved by chemotherapy and radiotherapy, avoiding the local spill of malignant
      cells.

PMID- 26308635
TI  - Impact of Cognitive Dysfunction on Survival in Patients With and Without Statin
      Use Following Carotid Endarterectomy.
AB  - BACKGROUND: Early cognitive dysfunction (eCD) is a subtle form of neurological
      injury observed in ~25% of carotid endarterectomy (CEA) patients. Statin use is
      associated with a lower incidence of eCD in asymptomatic patients having CEA.
      OBJECTIVE: To determine whether eCD status is associated with worse long-term
      survival in patients taking and not taking statins. METHODS: This is a post hoc
      analysis of a prospective observational study of 585 CEA patients. Patients were
      evaluated with a battery of neuropsychometric tests before and after surgery.
      Survival was compared for patients with and without eCD stratifying by statin
      use. At enrollment, 366 patients were on statins and 219 were not. Survival was
      assessed by using Kaplan-Meier methods and multivariable Cox proportional hazards
      models. RESULTS: Age >=75 years (P = .003), diabetes mellitus (P < .001), cardiac
      disease (P = .02), and statin use (P = .014) are significantly associated with
      survival univariately (P < .05) by use of the log-rank test. By Cox proportional
      hazards model, eCD status and survival adjusting for univariate factors within
      statin and nonstatin use groups suggested a significant effect by association of
      eCD on survival within patients not taking statin (hazard ratio, 1.61; 95%
      confidence interval, 1.09-2.40; P = .018), and no significant effect of eCD on
      survival within patients taking statin (hazard ratio, 0.98; 95% confidence
      interval, 0.59-1.66; P = .95). CONCLUSION: eCD is associated with shorter
      survival in patients not taking statins. This finding validates eCD as an
      important neurological outcome and suggests that eCD is a surrogate measure for
      overall health, comorbidity, and vulnerability to neurological insult.
      ABBREVIATIONS: aHR, adjusted hazards ratiosCEA, carotid endarterectomyCI,
      confidence intervalDM, diabetes mellituseCD, early cognitive dysfunctionNDI,
      National Death IndexNLR, neutrophil/lymphocyte ratioSD, standard deviationSEM,
      standard error of the mean.

PMID- 26308636
TI  - Letter: Advanced Hemostatics in the Management of Cerebral Dural Sinus
      Lacerations.

PMID- 26308637
TI  - In Reply: Advanced Hemostatics in the Management of Cerebral Dural Sinus
      Lacerations.

PMID- 26308638
TI  - Maintenance of Stemlike Glioma Cells and Microglia in an Organotypic Glioma Slice
      Model.
AB  - BACKGROUND: The therapeutic resistance of gliomas is, at least in part, due to
      stemlike glioma cells (SLGCs), which self-renew, generate the bulk of tumor
      cells, and sustain tumor growth. SLGCs from glioblastomas (GB) have been studied
      in cell cultures or mouse models, whereas little is known about SLGCs from lower
      grade gliomas. OBJECTIVE: To compare cell and organotypic slice cultures from GBs
      and lower grade gliomas and study the maintenance of SLGCs. METHODS: Cells and
      tissue slices from astrocytomas, oligodendrogliomas, oligoastrocytomas, and GBs
      were cultivated in (1) serum-free medium supplemented with the growth factors
      epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF), (2)
      medium containing 10% serum plus EGF and bFGF (F+GF medium), or (3) medium
      containing 10% fetal calf serum (F medium). Maintenance of cells and
      cytoarchitecture was addressed, using several candidate SLGC markers (Nestin,
      Sox2, CD133, CD44, CD49f/integrin alpha6, and Notch) as well as CD31 (endothelial
      cells), ionized calcium-binding adapter molecule 1 (microglia), and vimentin.
      Cell vitality was determined. RESULTS: SLGCs were present in tissue slices from
      lower and higher grade gliomas. Preservation of the cytoarchitecture in slices
      was possible for >3 weeks. Maintenance of SLGCs required the presence of EGF/bFGF
      in cell and slice cultures, in which F+GF appeared superior to N medium.
      Constraints were observed regarding the preservation of the microglia but not of
      the endothelial cells. Maintenance of the microglia was improved by addition of
      the cytokine macrophage colony-stimulating factor. CONCLUSION: Medium
      supplemented with serum and growth factors EGF, bFGF, and macrophage colony
      stimulating factor permits the preservation of SLGCs and non-SLGCs in the
      original glioma microenvironment.

PMID- 26308639
TI  - In Reply: Tissue-Glue-Coated Collagen Sponge (TachoSil) for Minor Cerebral Dural
      Venous Sinus Laceration: What is the Evidence?

PMID- 26308640
TI  - Market-Based Health Care in Specialty Surgery: Finding Patient-Centered Shared
      Value.
AB  - : The US health care system is struggling with rising costs, poor outcomes,
      waste, and inefficiency. The Patient Protection and Affordable Care Act
      represents a substantial effort to improve access and emphasizes value-based
      care. Value in health care has been defined as health outcomes for the patient
      per dollar spent. However, given the opacity of health outcomes and cost, the
      identification and quantification of patient-centered value is problematic. These
      problems are magnified by highly technical, specialized care (eg, neurosurgery).
      This is further complicated by potentially competing interests of the 5 major
      stakeholders in health care: patients, doctors, payers, hospitals, and
      manufacturers. These stakeholders are watching with great interest as health care
      in the United States moves toward a value-based system. Market principles can be
      harnessed to drive costs down, improve outcomes, and improve overall value to
      patients. However, there are many caveats to a market-based, value-driven system
      that must be identified and addressed. Many excellent neurosurgical efforts are
      already underway to nudge health care toward increased efficiency, decreased
      costs, and improved quality. Patient-centered shared value can provide a
      philosophical mooring for the development of health care policies that utilize
      market principles without losing sight of the ultimate goals of health care, to
      care for patients.

PMID- 26308641
TI  - High-Risk Factors in Symptomatic Patients Undergoing Carotid Artery Stenting With
      Distal Protection: Buffalo Risk Assessment Scale (BRASS).
AB  - BACKGROUND: Demographics and vascular anatomy may play an important role in
      predicting periprocedural complications in symptomatic patients undergoing
      carotid artery stenting (CAS). OBJECTIVE: To predict factors associated with
      increased risk of complications in symptomatic patients undergoing CAS and to
      devise a CAS scoring system that predicts such complications in this patient
      population. METHODS: A retrospective study was conducted that included patients
      who underwent CAS for symptomatic carotid stenosis during a 3-year period.
      Demographics and anatomic characteristics were subsequently correlated with 30
      day outcome measures. RESULTS: A total of 221 patients were included in the
      study. The cumulative rate of periprocedural complications was 7.2%, including
      stroke (3.2%), myocardial infarction (3.2%), and death (1.4%). Renal disease
      increased the risk of all complications. National Institutes of Health Stroke
      Scale score >=10 at presentation, difficult femoral access, and diseased
      calcified aortic arch increased the risk of stroke and all complications. Type
      III aortic arch correlated with increased risk of stroke. Pseudo-occlusion and
      concentric calcification of the carotid artery increased the risk of myocardial
      infarction, death, and all complications. Carotid tortuosity and anatomy hostile
      to the deployment of distal protection devices increased the risk of stroke,
      myocardial infarction, death, and all complications. CONCLUSION: Our results
      suggest that CAS should be avoided in patients with multiple anatomic risk
      factors. High presenting National Institutes of Health Stroke Scale score and
      renal disease also increase the complication risk. The CAS scoring system devised
      here is simple, reproducible, and clinically valuable in predicting complications
      risk in symptomatic patients undergoing CAS.

PMID- 26308642
TI  - Endovascular Therapy for Ruptured Cerebral Aneurysms in the Elderly: Poor
      Accessibility of the Guiding Catheter and Use of Local Anesthesia as the
      Predictors of Procedure-Related Rupture.
AB  - BACKGROUND: Endovascular therapy is favored for ruptured intracranial aneurysms
      in the elderly. However, poor accessibility to the aneurysm through the parent
      artery and use of local anesthesia in this age group may predispose to
      intraprocedural complications. OBJECTIVE: To evaluate whether age-related poor
      access to the ruptured target aneurysm and use of local anesthesia are associated
      with increased incidence of procedure-related rupture during endovascular
      embolization. METHODS: A total of 117 patients with 117 ruptured aneurysms
      underwent endovascular embolization at a single institution. Correlation of
      increasing age with poor accessibility of the guiding catheter was analyzed. In
      addition, the distance from the aneurysm to the guiding catheter was investigated
      to identify an association with incidence of procedure-related rupture.
      Correlation of local anesthesia with procedure-related rupture was also evaluated
      in the multivariable analysis. RESULTS: Increasing age was significantly
      associated with poor accessibility of the guiding catheter (P = .001, Mann
      Whitney U test). Procedure-related rupture occurred in 9 of 117 aneurysms (7.7%).
      Longer distance between distal aneurysms and low-positioned guiding catheters
      carried a higher risk of procedure-related rupture than a shorter distance
      between proximal aneurysms and high-positioned guiding catheters (odds ratio,
      19.3; 95% confidence interval, 1.84-201; P = .01, multivariable analysis). Use of
      local anesthesia was also a significant risk factor of procedure-related rupture
      by multivariable analysis. CONCLUSION: Increasing age was correlated with poor
      accessibility of the guiding catheter in endovascular embolization of ruptured
      intracranial aneurysms. Distally located aneurysms treated through a low
      positioned guiding catheter and use of local anesthesia increased the risk of
      procedure-related rupture.

PMID- 26308643
TI  - Treatment of Ruptured Anterior Communicating Artery Aneurysms: Equipoise in the
      Endovascular Era?
AB  - BACKGROUND: Ruptured anterior communicating artery (ACoA) aneurysms are
      heterogeneous intracranial aneurysms whose diverse morphological features
      influence treatment modality. OBJECTIVE: To compare clinical outcomes and
      complications of all ruptured ACoA aneurysms treated by clipping or coiling in a
      modern institutional trial. METHODS: All patients with ruptured ACoA aneurysms in
      the Barrow Ruptured Aneurysm Trial were included. Clinical follow-up at 1 and 3
      years was analyzed; charts were reviewed for patient demographics, aneurysm
      characteristics, and in-hospital complications. RESULTS: This cohort included 130
      patients (mean age, 52.5 years). Mean aneurysm size was 5.8 mm. Most aneurysm
      domes projected anteriorly (n = 52). After randomization and crossover, 91 ACoA
      aneurysms (70%) were clipped and 39 (30%) were coiled. Twenty-two patients
      (16.9%) initially randomized to coiling crossed over to clipping after
      evaluation. No patients crossed over from clipping to coiling. Characteristics
      precluding aneurysms from coiling included unfavorable dome-to-neck ratio,
      lesions difficult to access by catheter, and branch vessel involvement. Aneurysm
      size and dome projection were not significantly associated with treatment group,
      clinical outcome, or retreatment. No significant difference existed in clinical
      outcome (modified Rankin Scale scores) between groups at discharge or at 1-year
      or 3-year follow-up using as-treated and intention-to-treat analyses. Retreatment
      was performed in 3 clipped patients (2.3%) and 3 coiled patients (2.3%).
      CONCLUSION: Ruptured ACoA aneurysms, regardless of size and projection, were
      safely treated by both treatment modalities in a large-scale randomized clinical
      trial. Clinical outcomes and stroke rates did not differ significantly in as
      treated or intention-to-treat analyses.

PMID- 26308644
TI  - Association of a Distal Intradural-Extracranial Posterior Inferior Cerebellar
      Artery Aneurysm With Chiari Type I Malformation: Case Report.
AB  - BACKGROUND AND IMPORTANCE: Distal extracranial posterior inferior cerebellar
      artery (PICA) aneurysms are very rare lesions and have not been previously
      reported in association with a Chiari type I malformation (CMI). CLINICAL
      PRESENTATION: A 56-year-old woman with a distal, low-lying, intradural
      extracranial PICA aneurysm presented with a subarachnoid hemorrhage and was
      treated with coil embolization. The patient presented again 1 month later with
      symptoms of a CMI and was found to have tonsillar herniation and a large syrinx
      that appeared to be exacerbated by the coil mass. The patient was re-treated with
      a suboccipital craniectomy, C1-2 laminectomy, aneurysm trapping and excision, end
      to-end PICA anastomosis, and expansile duraplasty. CONCLUSION: Although just a
      single case, important teaching points regarding the angiographic appearance of a
      CMI and treatment options for distal PICA aneurysms that are situated below the
      foramen magnum can be learned. A low-lying caudal PICA loop should trigger a
      workup for a CMI. Caution should be taken when using coil embolization for
      aneurysms in the high cervical spinal canal. Bypass with aneurysm trapping and
      excision may be a superior treatment option in these cases because the posterior
      fossa and high cervical canal can be concomitantly decompressed. To our
      knowledge, this is the only case reported of a distal intradural-extracranial
      PICA aneurysm associated with a CMI.

PMID- 26308645
TI  - A Practical Methodological Approach Towards Identifying Core Competencies in
      Medical Education Based on Literature Trends: A Feasibility Study Based on
      Vestibular Schwannoma Science.
AB  - BACKGROUND: Competency-based medical education (CBME) is gaining momentum in
      postgraduate residency and fellowship training. While randomized trials,
      consensus statements, and practice guidelines can help delineate some of the core
      competencies for CBME, they are not applicable to all clinical scenarios.
      OBJECTIVE: To propose and assess the feasibility of a practical methodology for
      addressing this issue using radiosurgery for vestibular schwannoma (VS) science
      as an example. METHODS: The Web of Science electronic database was searched using
      relevant terms. A 3-step review of titles and abstracts was used. Studies were
      classified independently and in duplicate as either efficacy or effectiveness
      analyses. Cohen's kappa score was used to assess inter-rater agreement. RESULTS:
      Overall, 1818 surgical and 943 radiosurgical publications were identified. The
      number of effectiveness studies surpassed that of efficacy studies in the late
      1980s for surgical studies, and in the early-to-mid 1990s among radiosurgical
      studies. The publication rate was higher for radiosurgery in the mid 1990s, but
      it paralleled that of surgical studies beyond the early 2000s. Variations in this
      overall trend corresponded to the emergence of studies that assessed the role of
      endoscopy and the utility of dose reduction in radiosurgery. CONCLUSION: We have
      confirmed the feasibility and accuracy of this objective methodological approach.
      By understanding how the peer-reviewed literature reflects actual practice
      interests, educators can tailor curricula to ensure that trainees remain current.
      While further validation studies are needed, this methodology can serve as a
      supplemental strategy for identifying additional core competencies in CBME.

PMID- 26308646
TI  - Wood Usage and Fire Veneration in the Pamir, Xinjiang, 2500 yr BP.
AB  - Located on the Pamir Plateau in Xinjiang Province, China, the Ji'erzankale
      Necropolis dates back to 2500 yr BP. Many materials that have been unearthed in
      this cemetery, including shoo konghou (musical instrument), bronze mirrors and
      glass beads, suggest cultural transference between East and West. Furthermore,
      small-sized and rounded fire altars made from sweet-scented Sabina were found for
      the first time and regarded as implements for fire veneration. We identified 70
      wooden objects from 25 tombs within the Necropolis, and found that each object
      had been made from one of seven tree species. Analysis revealed that the
      inhabitants of the region mainly used the most widely available types of wood,
      namely Betula and Populus. People also specifically chose inflammable Populus
      wood to make hearth boards and hand drills (both are used for making fire by
      drilling), rigid Betula wood to craft wooden plates. Salix was used for
      fashioning wooden sticks, while sweet-scented Sabina was the preferred choice for
      making fire altars. Lonicera was selected for arrow shaft manufacture and
      Fraxinus syriaca, which has a beautiful grain, was chosen for making musical
      instruments. Conscious selection of different types of wood indicates that people
      of the Pamir Plateau were aware of the properties of various types of timbers,
      and were able to exploit these properties to the full. In turn, this demonstrates
      their wisdom and their ability to survive in, and adapt to, their local
      environment. 

PMID- 26308647
TI  - Fluid Shear Stress Upregulates E-Tmod41 via miR-23b-3p and Contributes to F-Actin
      Cytoskeleton Remodeling during Erythropoiesis.
AB  - The membrane skeleton of mature erythrocyte is formed during erythroid
      differentiation. Fluid shear stress is one of the main factors that promote
      embryonic hematopoiesis, however, its effects on erythroid differentiation and
      cytoskeleton remodeling are unclear. Erythrocyte tropomodulin of 41 kDa (E
      Tmod41) caps the pointed end of actin filament (F-actin) and is critical for the
      formation of hexagonal topology of erythrocyte membrane skeleton. Our study
      focused on the regulation of E-Tmod41 and its role in F-actin cytoskeleton
      remodeling during erythroid differentiation induced by fluid shear stress. Mouse
      erythroleukemia (MEL) cells and embryonic erythroblasts were subjected to fluid
      shear stress (5 dyn/cm2) and erythroid differentiation was induced in both cells.
      F-actin content and E-Tmod41 expression were significantly increased in MEL cells
      after shearing. E-Tmod41 overexpression resulted in a significant increase in F
      actin content, while the knockdown of E-Tmod41 generated the opposite result. An
      E-Tmod 3'UTR targeting miRNA, miR-23b-3p, was found suppressed by shear stress.
      When miR-23b-3p level was overexpressed / inhibited, both E-Tmod41 protein level
      and F-actin content were reduced / augmented. Furthermore, among the two
      alternative promoters of E-Tmod, PE0 (upstream of exon 0), which mainly drives
      the expression of E-Tmod41, was found activated by shear stress. In conclusion,
      our results suggest that fluid shear stress could induce erythroid
      differentiation and F-actin cytoskeleton remodeling. It upregulates E-Tmod41
      expression through miR-23b-3p suppression and PE0 promoter activation, which, in
      turn, contributes to F-actin cytoskeleton remodeling. 

PMID- 26308648
TI  - Guard cell hydrogen peroxide and nitric oxide mediate elevated CO2 -induced
      stomatal movement in tomato.
AB  - Climate change as a consequence of increasing atmospheric CO2 influences plant
      photosynthesis and transpiration. Although the involvement of stomata in plant
      responses to elevated CO2 has been well established, the underlying mechanism of
      elevated CO2 -induced stomatal movement remains largely unknown. We used diverse
      techniques, including laser scanning confocal microscopy, transmission electron
      microscopy, biochemical methodologies and gene silencing to investigate the
      signaling pathway for elevated CO2 -induced stomatal movement in tomato (Solanum
      lycopersicum). Elevated CO2 -induced stomatal closure was dependent on the
      production of RESPIRATORY BURST OXIDASE 1 (RBOH1)-mediated hydrogen peroxide (H2
      O2 ) and NITRATE REDUCTASE (NR)-mediated nitric oxide (NO) in guard cells in an
      abscisic acid (ABA)-independent manner. Silencing of OPEN STOMATA 1 (OST1)
      compromised the elevated CO2 -induced accumulation of H2 O2 and NO, upregulation
      of SLOW ANION CHANNEL ASSOCIATED 1 (SLAC1) gene expression and reduction of
      stomatal aperture, whereas silencing of RBOH1 or NR had no effects on the
      expression of OST1. Our results demonstrate that as critical signaling molecules,
      RBOH1-dependent H2 O2 and NR-dependent NO act downstream of OST1 that regulate
      SLAC1 expression and elevated CO2 -induced stomatal movement. This information is
      crucial to deepen the understanding of CO2 signaling pathway in guard cells. 

PMID- 26308649
TI  - The Effect of Sex and Age on Small Intestinal Transit Times in Humans.
AB  - This study utilizes a novel approach of small bowel video capsule endoscopy for
      investigating the influence of sex and age on small intestinal transit times
      (SITT) in humans. A total of 81 outpatients undergoing investigations with the
      small bowel video capsule endoscope (SB-VCE) and meeting inclusion criteria were
      included in this study. Following an overnight fast, patients swallowed the SB
      VCE with a glass of water. SITT were calculated from the first duodenal image to
      the first cecal image. This study showed that the SB-VCE provides accurate and
      reliable measurements of SITT under real-life conditions. A large inter
      individual variability in SITT was observed, with times ranging from 50 to 460
      min. This variability can have implications on drug absorption and
      bioavailability. The median SITT were 219 min for females and 191 min for males.
      Although SITT were 28 min longer in females than males, this difference was not
      found to be statistically significant (p = 0.66). No correlation was found
      between age and SITT (Pearson correlation coefficient 0.19). Therefore, any drug
      bioavailability differences of modified release dosage preparations that are
      observed between adult patient groups of different age or sex are unlikely to be
      attributable to SITT.

PMID- 26308650
TI  - Ortho-Stabilized (18) F-Azido Click Agents and their Application in PET Imaging
      with Single-Stranded DNA Aptamers.
AB  - Azido (18) F-arenes are important and versatile building blocks for the
      radiolabeling of biomolecules via Huisgen cycloaddition ("click chemistry") for
      positron emission tomography (PET). However, routine access to such clickable
      agents is challenged by inefficient and/or poorly defined multistep radiochemical
      approaches. A high-yielding direct radiofluorination for azido (18) F-arenes was
      achieved through the development of an ortho-oxygen-stabilized iodonium
      derivative (OID). This OID strategy addresses an unmet need for a reliable azido
      (18) F-arene clickable agent for bioconjugation reactions. A ssDNA aptamer was
      radiolabeled with this agent and visualized in a xenograft mouse model of human
      colon cancer by PET, which demonstrates that this OID approach is a convenient
      and highly efficient way of labeling and tracking biomolecules. 

PMID- 26308652
TI  - Political psychology.
AB  - Political psychology is a dynamic field of research that offers a unique blend of
      approaches and methods in the social and cognitive sciences. Political
      psychologists explore the interactions between macrolevel political structures
      and microlevel factors such as decision-making processes, motivations, and
      perceptions. In this article, we provide a broad overview of the field, beginning
      with a brief history of political psychology research and a summary of the
      primary methodological approaches in the field. We then give a more detailed
      account of research on ideology and social justice, two topics experiencing a
      resurgence of interest in current political psychology. Finally, we cover
      research on political persuasion and voting behavior. By summarizing these major
      areas of political psychology research, we hope to highlight the wide variety of
      theoretical and methodological approaches of cognitive scientists working at the
      intersection of psychology and political science. WIREs Cogn Sci 2014, 5:373-385.
      doi: 10.1002/wcs.1293 For further resources related to this article, please visit
      the WIREs website. CONFLICT OF INTEREST: The authors have declared no conflicts
      of interest for this article.

PMID- 26308653
TI  - Anxiety and cognition.
AB  - In this review we discuss the interplay between anxiety and cognition,
      illustrating how anxiety can compromise performance on cognitively-demanding
      tasks and lead people to perform below their ability. Using math anxiety and test
      anxiety as examples, we highlight key findings from psychology, cognitive
      science, and neuroscience, to show that how one approaches an anxiety-inducing
      situation can have a large impact on how that person ultimately performs. We end
      by discussing who is most susceptible to anxiety-induced poor performance and
      suggest promising techniques which may help to reduce the negative impact of
      anxiety on performance. WIREs Cogn Sci 2014, 5:403-411. doi: 10.1002/wcs.1299
      CONFLICT OF INTEREST: The authors have declared no conflicts of interest for this
      article. For further resources related to this article, please visit the WIREs
      website. 

PMID- 26308651
TI  - Cross-Talk Between Human Tenocytes and Bone Marrow Stromal Cells Potentiates
      Extracellular Matrix Remodeling In Vitro.
AB  - Tendon and ligament (T/L) pathologies account for a significant portion of
      musculoskeletal injuries and disorders. Tissue engineering has emerged as a
      promising solution in the regeneration of both tissues. Specifically, the use of
      multipotent human mesenchymal stromal cells (hMSC) has shown great promise to
      serve as both a suitable cell source for tenogenic regeneration and a source of
      trophic factors to induce tenogenesis. Using four donor sets, we investigated the
      bidirectional paracrine tenogenic response between human hamstring tenocytes
      (hHT) and bone marrow-derived hMSC. Cell metabolic assays showed that only one
      hHT donor experienced sustained notable increases in cell metabolic activity
      during co-culture. Histological staining confirmed that co-culture induced
      elevated collagen protein levels in both cell types at varying time-points in two
      of four donor sets assessed. Gene expression analysis using qPCR showed the
      varied up-regulation of anabolic and catabolic markers involved in extracellular
      matrix maintenance for hMSC and hHT. Furthermore, analysis of hMSC/hHT co-culture
      secretome using a reporter cell line for TGF-beta, a potent inducer of
      tenogenesis, revealed a trend of higher TGF-beta bioactivity in hMSC secretome
      compared to hHT. Finally, hHT cytoskeletal immunostaining confirmed that both
      cell types released soluble factors capable of inducing favorable tenogenic
      morphology, comparable to control levels of soluble TGF-beta1. These results
      suggest a potential for TGF-beta-mediated signaling mechanism that is involved
      during the paracrine interplay between the two cell types that is reminiscent of
      T/L matrix remodeling/turnover. These findings have significant implications in
      the clinical use of hMSC for common T/L pathologies.

PMID- 26308654
TI  - Causal learning in children.
AB  - How do children learn the causal structure of the environment? We first summarize
      a set of theories from the adult literature on causal learning, including
      associative models, parameter estimation theories, and causal structure learning
      accounts, as applicable to developmental science. We focus on causal graphical
      models as a description of children's causal knowledge, and the implications of
      this computational description for children's causal learning. We then examine
      the contributions of explanation and exploration to causal learning from a
      computational standpoint. Finally, we examine how children might learn causal
      knowledge from others and how computational and constructivist accounts of causal
      learning can be integrated. WIREs Cogn Sci 2014, 5:413-427. doi: 10.1002/wcs.1291
      For further resources related to this article, please visit the WIREs website.
      CONFLICT OF INTEREST: The authors have declared no conflicts of interest for this
      article.

PMID- 26308655
TI  - Cultural context of cognitive development.
AB  - The cognitive problems that children formulate and solve in their daily lives
      necessarily take form in a cultural context. We review and illustrate two
      dominant approaches to study relations between cultural context and cognitive
      development, and we point to the limitations and affordances of each. Using a
      dichotomous approach, scholars employ a methodology that sharply differentiates
      cognition from cultural context, treating elements of cultural context as
      independent variables and elements of cognition as dependent variables. The
      approach often leads to propositions about transcultural features of context that
      influence the cognitive development of individuals. In contrast, using an
      intrinsic relations approach, researchers create units of analysis that capture
      relations between cognition and cultural context, investigating their mutual
      grounding in daily activities. We also review a small but important body of
      research that extends these approaches to diachronic analysis. This research
      seeks to understand shifting relations between cultural context and cognitive
      development over historical time. WIREs Cogn Sci 2014, 5:447-461. doi:
      10.1002/wcs.1300 For further resources related to this article, please visit the
      WIREs website. CONFLICT OF INTEREST: The authors have declared no conflicts of
      interest for this article.

PMID- 26308656
TI  - Human diet and cognition.
AB  - Cognition influences what, when and how much we eat, which in turn affects the
      brain and hence cognition. In this overview, focusing mainly on the human
      literature, we start by examining cognitive influences on food and eating. This
      includes food preferences and choices (e.g., effects of learning, advertising,
      and cultural taboos), food habits relating to when and how much to eat (e.g., the
      concept of meals, dieting, and hunger strikes), the perception of food (e.g., the
      influence of appearance, food labels, and conceptions of naturalness), and how
      food perception is influenced by expertise. We also review how these various
      influences are disrupted by abnormalities of cognition (e.g., Gourmand syndrome,
      amnesia, and anorexia nervosa). The second part of the overview focuses on how
      diet affects cognition. We start by looking at the acute effects of diet, notably
      the impact of breakfast on cognitive performance in children. This is followed by
      a review of the effects of extended dietary exposures-years and lifetimes of
      particular diets. Here we look at the impacts of protein-energy malnourishment
      and Western-style diets, and their different, but adverse affects on cognition,
      and the beneficial effects on cognition of breast-feeding and certain dietary
      practices. We then outline how diet and cooking may have allowed the evolution of
      the large energy-hungry human brain. This overview serves to illustrate the
      multiple interactions that exist between cognition and diet, their importance to
      health and disease, and their impact on thinking about the role of conscious
      processes in decision making. WIREs Cogn Sci 2014, 5:463-475. doi:
      10.1002/wcs.1290 For further resources related to this article, please visit the
      WIREs website. CONFLICT OF INTEREST: The authors have declared no conflicts of
      interest for this article.

PMID- 26308657
TI  - Cognitive processing, language typology, and variation.
AB  - Linguistic typological preferences have often been linked to cognitive processing
      preferences but often without recourse to typologically relevant experiments on
      cognitive processing. This article reviews experimental work on the possible
      parallels between preferences in cognitive processing and language typology. I
      summarize the main theoretical accounts of the processing-typology connection and
      show that typological distributions arise diachronically from preferred paths of
      language change, which may be affected by the degree to which alternative
      structures are preferred (e.g., easier) in acquisition or usage. The surveyed
      experimental evidence shows that considerable support exists for many linguistic
      universals to reflect preferences in cognitive processing. Artificial language
      learning experiments emerge as a promising method for researching the processing
      typology connection, as long as its limitations are taken into account. I further
      show that social and cultural differences in cognition may have an effect on
      typological distributions and that to account for this variation a
      multidisciplinary approach to the processing-typology connection has to be
      developed. Lastly, since the body of experimental research does not adequately
      represent the linguistic diversity of the world's languages, it remains as an
      urgent task for the field to better account for this diversity in future work.
      WIREs Cogn Sci 2014, 5:477-487. doi: 10.1002/wcs.1294 For further resources
      related to this article, please visit the WIREs website. CONFLICT OF INTEREST:
      The author has declared no conflicts of interest for this article.

PMID- 26308658
TI  - Prospects for usage-based computational models of grammatical development:
      argument structure and semantic roles.
AB  - The computational modeling of language development has enabled researchers to
      make impressive strides toward achieving a comprehensive psychological account of
      the processes and mechanisms whereby children acquire their mother tongues.
      Nevertheless, the field's primary focus on distributional information has lead to
      little progress in elucidating the processes by which children learn to compute
      meanings beyond the level of single words. This lack of psychologically motivated
      computational work on semantics poses an important challenge for usage-based
      computational accounts of acquisition in particular, which hold that grammatical
      development is closely tied to meaning. In the present review, we trace some
      initial steps toward answering this challenge through a survey of existing
      computational models of grammatical development that incorporate semantic
      information to learn to assign thematic roles and acquire argument structure. We
      argue that the time is ripe for usage-based computational accounts of grammatical
      development to move beyond purely distributional features of the input, and to
      incorporate information about the objects and actions observable in the learning
      environment. To conclude, we sketch possible avenues for extending previous
      approaches to modeling the role of semantics in grammatical development. WIREs
      Cogn Sci 2014, 5:489-499. doi: 10.1002/wcs.1295 For further resources related to
      this article, please visit the WIREs website. CONFLICT OF INTEREST: The authors
      have declared no conflicts of interest for this article.

PMID- 26308660
TI  - Single-crystal-conjugated polymers with extremely high electron sensitivity
      through template-assisted in situ polymerization.
AB  - Single-crystal-conjugated polymer (SCCP) arrays are prepared successfully via a
      simple method, which is a combination of the contact thermochemical reaction and
      solvent-free in situ polymerization. The dramatic X-ray diffraction and selective
      area electron diffraction results show the high crystallinity of the SCCP arrays.
      These SCCP arrays display unique physical properties and show great potential in
      flexible electronics. 

PMID- 26308661
TI  - A spatial mismatch between invader impacts and research publications.

PMID- 26308662
TI  - Gestational diabetes and the risk of subsequent Type 2 diabetes in Australian
      Aboriginal women living in a remote community.

PMID- 26308663
TI  - A novel method to prevent recurrent balloon rupture during dilation of heavily
      calcified conduits in preparation for transcatheter pulmonary valve placement.
AB  - INTRODUCTION: A 24-year-old female presented for percutaneous pulmonary valve
      placement. She was born with tetralogy of Fallot and had initial palliation with
      a Blalock-Taussig shunt followed by complete repair at age of 4 years including
      placement of a homograft conduit in the right ventricle to pulmonary artery
      position. She had developed severe obstruction in the conduit. PROCEDURE:
      Angiography showed a heavily calcified conduit with moderate insufficiency.
      During pre-dilation, a total of six balloons ruptured due to heavy conduit
      calcification prior to reaching desired inflation diameter. Subsequently, double
      balloon technique was attempted using two 9-mm Conquest balloons. One of the
      conquest balloons was then replaced by 16-mm Atlas balloon and conduit dilation
      was performed. At full inflation, the Conquest balloon ruptured. The deflated
      ruptured Conquest balloon was kept in the conduit and the Atlas balloon was
      exchanged for 18 and then 20-mm Atlas balloons and both were used to dilate the
      conduit. The deflated ruptured Conquest balloon protected the Atlas balloons and
      conduit angioplasty proceeded successfully without further rupture of any
      balloon. Subsequently, four stents were placed in the conduit followed by
      delivery of Melody Valve using a 20-mm Ensemble system with excellent results.
      CONCLUSION: This case illustrates a novel method of using the body of a ruptured
      balloon to protect subsequent balloons from rupture due to heavy conduit
      calcification. This method requires the presence of two venous access lines but
      might save time, effort, and cost from repeated balloon ruptures.

PMID- 26308664
TI  - Laser applications for benign oral lesions.
AB  - BACKGROUND AND OBJECTIVE: Different subspecialists treat benign intraoral lesions
      using various approaches including surgical excision, medical therapy,
      sclerotherapy, and laser photocoagulation. The goal of this study was to
      establish whether lasers could effectively target and destroy oral lesions
      containing endogenous chromophores, while minimizing injury to unaffected
      adjacent tissues and critical structures. MATERIALS AND METHODS: This
      retrospective study involved 26 cases of benign oral lesions, both vascular and
      pigmented, which were addressed by means of selective laser treatment.
      Pathologies were port-wine stains, hereditary hemorragic teleangectasia,
      hemangiomas, venous and arteriovenous malformations, pyogenic granuloma, and
      hairy reconstructive flaps. Electronic medical records and photographic
      documentation were reviewed. Three blinded staff personnel not involved with
      patient care in this study evaluated photographs taken prior to the first and
      after the final laser treatments. Observers rated the percentage clearance of the
      lesions or the ablation of bleeding, and the assessed values were averaged for
      each patient. RESULTS: An average of 30-95% lightening was observed in the
      intraoral port-wine stains, 90% in the hemangiomas, 70% in arteriovenous
      malformations, 81% for venous malformations, 86% for venous lakes, and 100% for
      the pyogenic granuloma. Bleeding was ablated in all hereditary hemorrhagic
      telangiectasia lesions treated using the pulsed dye laser with or without the
      Alexandrite laser. Intraoral hair growing on the skin paddle of microvascular
      flaps was completely removed in one of the three cases treated using the
      Alexandrite laser. In the two remaining cases, some hair removal was achieved,
      but because the residual hairs were grey or white (absence of melanocytic
      chromophore), photocoagulation was less effective. CONCLUSION: Lasers are a safe
      and effective means to selectively destroy specific chromphores. Such specific
      targeting ensures complete destruction of pathological tissue, decreasing the
      possibility of relapse and/or recurrence. Selective laser treatment of benign
      intraoral lesions represents a niche application that fills a gap in the
      multidisciplinary management of several conditions such as oral vascular
      anomalies and hairy reconstructive flaps.

PMID- 26308665
TI  - Which goal adjustment strategies do cancer patients use? A longitudinal study.
AB  - OBJECTIVE: A cancer diagnosis may lead to the need to adjust personal goals. This
      study longitudinally investigates patients' use of goal adjustment strategies
      with goal characteristics over time. Whether and which goal adjustment strategies
      are used after cancer diagnosis may depend on the period studied (treatment
      period or follow-up period) and illness variables such as illness severity.
      METHODS: Newly diagnosed colorectal cancer patients (n = 186) were asked about
      their personal goals during three assessments (within 1 month after diagnosis and
      6 and 18 months after the first assessment). Eight goal adjustment strategies
      were assessed over the first 6 months (treatment period) and between 7 and 18
      months (follow-up period) using goal characteristics. Illness variables were
      obtained from patients' medical records from the national cancer registry.
      RESULTS: Most patients used one strategy per period, and patients most often
      shifted their priorities across life domains. During the treatment period, more
      patients formed shorter-term goals than during the follow-up period, while during
      the follow-up period, more patients formed longer-term goals than during the
      treatment period. Illness variables were not related to the use of goal
      adjustment strategies. CONCLUSIONS: The findings show that cancer patients use
      different goal adjustment strategies and, interestingly, that the use of specific
      strategies depended on the period after diagnosis but not on illness variables.

PMID- 26308666
TI  - In vivo hematopoietic Myc activation directs a transcriptional signature in
      endothelial cells within the bone marrow microenvironment.
AB  - Cancer pathogenesis involves tumor-intrinsic genomic aberrations and tumor-cell
      extrinsic mechanisms such as failure of immunosurveillance and structural and
      functional changes in the microenvironment. Using Myc as a model oncogene we
      established a conditional mouse bone marrow transduction/transplantation model
      where the conditional activation of the oncoprotein Myc expressed in the
      hematopoietic system could be assessed for influencing the host microenvironment.
      Constitutive ectopic expression of Myc resulted in rapid onset of a lethal
      myeloproliferative disorder with a median survival of 21 days. In contrast, brief
      4-day Myc activation by means of the estrogen receptor (ER) agonist tamoxifen did
      not result in gross changes in the percentage/frequency of hematopoietic lineages
      or hematopoietic stem/ progenitor cell (HSPC) subsets, nor did Myc activation
      significantly change the composition of the non-hematopoietic microenvironment
      defined by phenotyping for CD31, ALCAM, and Sca-1 expression. Transcriptome
      analysis of endothelial CD45- Ter119- cells from tamoxifen-treated MycER bone
      marrow graft recipients revealed a gene expression signature characterized by
      specific changes in the Rho subfamily pathway members, in the transcription
      translation-machinery and in angiogenesis. In conclusion, intra-hematopoietic Myc
      activation results in significant transcriptome alterations that can be
      attributed to oncogene-induced signals from hematopoietic cells towards the
      microenvironment, e. g. endothelial cells, supporting the idea that even pre
      leukemic HSPC highjack components of the niche which then could protect and
      support the cancer-initiating population. 

PMID- 26308667
TI  - Extent of resection and overall survival for patients with atypical and malignant
      meningioma.
AB  - BACKGROUND: The prognosis for patients with atypical and malignant meningioma is
      guarded; whether the extent of resection is associated with survival-based
      outcomes in this population remains poorly defined. This study investigated the
      association between gross total resection (GTR) and all-cause mortality in
      patients with atypical and malignant meningioma. METHODS: The Surveillance,
      Epidemiology, and End Results program was used to identify 575 and 64 patients
      betweens the ages of 18 and 70 years who were diagnosed with atypical and
      malignant meningioma, respectively, between 2004 and 2009. Multivariate Cox
      proportional hazards regression was used to assess the adjusted impact of GTR
      versus subtotal resection on all-cause mortality. RESULTS: Baseline patient
      characteristics were similar for patients who did undergo GTR and patients who
      did not undergo GTR. The 5-year overall survival rates were 91.3% (95% confidence
      interval [CI], 86.2%-94.5%) and 78.2% (95% CI, 70.0%-84.3%) for patients with
      atypical meningioma who did and did not undergo GTR, respectively, and 64.5% (95%
      CI, 45.9%-78.1%) and 41.1% (95% CI, 17.9%-63.1%) for patients with malignant
      meningioma who did and did not undergo GTR, respectively. After adjustments for
      available, pertinent confounding variables, GTR was associated with lower all
      cause mortality in patients with atypical (hazard ratio, 0.39; 95% CI, 0.23-0.67;
      P < .001) and malignant meningioma (hazard ratio, 0.35; 95% CI, 0.15-0.81; P =
      .01). CONCLUSIONS: The extent of resection is a powerful predictor of outcome for
      patients with atypical and malignant meningioma. These data highlight the hazard
      associated with the presence of gross tumor bulk after surgery and suggest a
      value for more extensive resections that should be balanced against the
      additional potential morbidity.

PMID- 26308668
TI  - Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy:
      Portal Vein Embolization Should Remain the Gold Standard.

PMID- 26308669
TI  - Photothermally Activated Pyroelectric Polymer Films for Harvesting of Solar Heat
      with a Hybrid Energy Cell Structure.
AB  - Photothermal effects in poly(3,4-ethylenedioxythiophene)s (PEDOTs) were explored
      for pyroelectric conversion. A poled ferroelectric film was coated on both sides
      with PEDOT via solution casting polymerization of EDOT, to give highly conductive
      and effective photothermal thin films of PEDOT. The PEDOT films not only provided
      heat source upon light exposure but worked as electrodes for the output energy
      from the pyroelectric layer in an energy harvester hybridized with a
      thermoelectric layer. Compared to a bare thermoelectric system under NIR
      irradiation, the photothermal-pyro-thermoelectric device showed more than 6 times
      higher thermoelectric output with the additional pyroelectric output. The
      photothermally driven pyroelectric harvesting film provided a very fast electric
      output with a high voltage output (Vout) of 15 V. The pyroelectric effect was
      significant due to the transparent and high photothermal PEDOT film, which could
      also work as an electrode. A hybrid energy harvester was assembled to enhance
      photoconversion efficiency (PCE) of a solar cell with a thermoelectric device
      operated by the photothermally generated heat. The PCE was increased more than
      20% under sunlight irradiation (AM 1.5G) utilizing the transmitted light through
      the photovoltaic cell as a heat source that was converted into pyroelectric and
      thermoelectric output simultaneously from the high photothermal PEDOT electrodes.
      Overall, this work provides a dynamic and static hybrid energy cell to harvest
      solar energy in full spectral range and thermal energy, to allow solar powered
      switching of an electrochromic display. 

PMID- 26308670
TI  - Diverse diuretics regimens differentially enhance the antialbuminuric effect of
      renin-angiotensin blockers in patients with chronic kidney disease.
AB  - The addition of spironolactone or hydrochlorothiazide enhances the
      antialbuminuric effect of renin-angiotensin blockers. However, comparative
      studies on the effect of different diuretics are lacking. We conducted a
      prospective randomized crossover study to compare the effects of spironolactone
      (25 mg/day), hydrochlorothiazide (50 mg/day) without/with amiloride (5 mg/day) on
      top of enalapril treatment in 21 patients with CKD stages 1-3 and a urinary
      albumin-to-creatinine ratio (UACR) over 300 mg/g. Treatment periods lasted 4
      weeks. The UACR showed a significant reduction with the diuretics:
      spironolactone, -34% or hydrochlorothiazide without/with amiloride -42% or -56%,
      respectively. Reduction of the UACR was significantly greater with
      hydrochlorothiazide without/with amiloride when compared with spironolactone. The
      percentage of patients who achieved UACR reductions greater than 30% and 50% was
      greater with hydrochlorothiazide without/with amiloride (81% and 57%, and 81% and
      66%, respectively) when compared with spironolactone alone (57% and 28%,
      respectively). Glomerular filtration rate (GFR), blood pressure, and body weight
      decreased with the three diuretic regimens. A significant correlation was found
      between the UACR reduction and GFR and blood pressure changes. Thus, diverse
      diuretic regimens differentially enhance albuminuria reduction, an effect likely
      associated with the degree of GFR reduction.

PMID- 26308671
TI  - Insulin sensitivity of muscle protein metabolism is altered in patients with
      chronic kidney disease and metabolic acidosis.
AB  - An emergent hypothesis is that a resistance to the anabolic drive by insulin may
      contribute to loss of strength and muscle mass in patients with chronic kidney
      disease (CKD). We tested whether insulin resistance extends to protein metabolism
      using the forearm perfusion method with arterial insulin infusion in 7 patients
      with CKD and metabolic acidosis (bicarbonate 19 mmol/l) and 7 control
      individuals. Forearm glucose balance and protein turnover (2H-phenylalanine
      kinetics) were measured basally and in response to insulin infused at different
      rates for 2 h to increase local forearm plasma insulin concentration by
      approximately 20 and 50 MUU/ml. In response to insulin, forearm glucose uptake
      was significantly increased to a lesser extent (-40%) in patients with CKD than
      controls. In addition, whereas in the controls net muscle protein balance and
      protein degradation were decreased by both insulin infusion rates, in patients
      with CKD net protein balance and protein degradation were sensitive to the high
      (0.035 mU/kg per min) but not the low (0.01 mU/kg per min) insulin infusion.
      Besides blunting muscle glucose uptake, CKD and acidosis interfere with the
      normal suppression of protein degradation in response to a moderate rise in
      plasma insulin. Thus, alteration of protein metabolism by insulin may lead to
      changes in body tissue composition which may become clinically evident in
      conditions characterized by low insulinemia.

PMID- 26308672
TI  - Evidence for a gastrointestinal-renal kaliuretic signaling axis in humans.
AB  - A gastrointestinal-renal kaliuretic signaling axis has been proposed to regulate
      potassium excretion in response to acute potassium ingestion independent of the
      extracellular potassium concentration and aldosterone. Here we studied this
      presumed axis in 32 individuals in our clinical pharmacology unit while on a 20
      mmol sodium and 60 mmol potassium diet. The serum potassium concentration,
      potassium excretion, aldosterone, and insulin were measured following either a 35
      mmol oral potassium load, a potassium- and sodium-deficient complex meal, or a
      potassium-deficient complex meal plus 35 mmol potassium. This design allowed
      determination of the component effects on potassium handling of the meal and
      potassium load separately. The meal plus potassium test was repeated following
      aldosterone blockade with eplerenone to specifically evaluate the role of
      aldosterone. In response to the potassium-deficient meal plus 35 mmol potassium,
      the serum potassium did not increase but the hourly mean potassium excretion
      increased sharply. This kaliuresis persisted following aldosterone blockade with
      eplerenone, further suggesting independence from aldosterone. Thus, a
      gastrointestinal-renal kaliuretic signaling axis exists in humans mediating
      potassium excretion independent of changes in the serum potassium concentration
      and aldosterone. The implication of this mechanism is yet to be determined but
      may account for a significant component of potassium excretion following a
      complex potassium-rich meal.

PMID- 26308673
TI  - Identification of the Amidase BbdA That Initiates Biodegradation of the
      Groundwater Micropollutant 2,6-dichlorobenzamide (BAM) in Aminobacter sp. MSH1.
AB  - 2,6-dichlorobenzamide (BAM) is a recalcitrant groundwater micropollutant that
      poses a major problem for drinking water production in European countries.
      Aminobacter sp. MSH1 and related strains have the unique ability to mineralize
      BAM at micropollutant concentrations but no information exists on the genetics of
      BAM biodegradation. An amidase-BbdA-converting BAM to 2,6-dichlorobenzoic acid
      (DCBA) was purified from Aminobacter sp. MSH1. Heterologous expression of the
      corresponding bbdA gene and its absence in MSH1 mutants defective in BAM
      degradation, confirmed its BAM degrading function. BbdA shows low amino acid
      sequence identity with reported amidases and is encoded by an IncP1-beta plasmid
      (pBAM1, 40.6 kb) that lacks several genes for conjugation. BbdA has a remarkably
      low KM for BAM (0.71 MUM) and also shows activity against benzamide and ortho
      chlorobenzamide (OBAM). Differential proteomics and transcriptional reporter
      analysis suggest the constitutive expression of bbdA in MSH1. Also in other BAM
      mineralizing Aminobacter sp. strains, bbdA and pBAM1 appear to be involved in BAM
      degradation. BbdA's high affinity for BAM and its constitutive expression are of
      interest for using strain MSH1 in treatment of groundwater containing
      micropollutant concentrations of BAM for drinking water production.

PMID- 26308674
TI  - Use of routine thoracic and abdominal computed tomography scans for assessing
      bone mineral density and detecting osteoporosis.
AB  - OBJECTIVE: Evaluation of computed tomography (CT) attenuation measurements for
      assessing bone mineral density (BMD) and predicting osteoporosis in thoracic and
      abdominal CT scans for various clinical indications using dual-energy X-ray
      absorptiometry (DXA) as reference standard. RESEARCH DESIGN AND METHODS: A total
      of 234 patients (147 women, 87 men) undergoing DXA and CT were examined
      retrospectively. Mean time between both studies was 0.5 years. CT-attenuation
      values in Hounsfield units (HU) were measured at the thoracic and lumbar spine
      (T1, T6, T12, L1-L5), at the femoral neck, and then assigned to their
      corresponding DXA scores. RESULTS: Patients with DXA-defined osteoporosis or
      osteopenia showed significantly lower HU values of trabecular bone at all
      measured levels compared to healthy subjects (p < 0.001). HU values were highest
      at T1 and T6, lowest at L1-L3 and the femoral neck. There were no significant
      intraindividual differences between HU values in the sagittal, coronal or
      transversal plane. Significant differences between normal and abnormal BMD
      categories were verified for three CT scanners. More than half of all fractures
      were detected in patients with non-osteoporotic DXA T-scores. CONCLUSIONS:
      Abdominal and particularly thoracic CT scans obtained for other clinical
      indications can sensibly be applied toward determining low BMD, detecting
      osteoporosis and identifying persons at increased fracture risk. Osteoporotic
      morbidity and mortality might be minimized. Superiorly to DXA, fragility
      fractures can be found without additional imaging or radiation exposure which can
      initiate early adequate treatment. LIMITATIONS: Key limitations of the study were
      as following: a retrospective, single-center study; small patient cohort - larger
      cohorts are needed to evaluate the sensitivity and specificity of diagnostic
      performance measurements; more complex CT evaluation of the hip for BMD
      assessment; DXA measurements were used as a reference standard, however, patients
      with unsuspected compression fractures but showing osteopenic or even normal BMD
      outline the limitations of DXA.

PMID- 26308675
TI  - Scripts and information units in future planning: Interactions between a past and
      a future planning task.
AB  - Research on future thinking has emphasized how episodic details from memories are
      combined to create future thoughts, but has not yet examined the role of semantic
      scripts. In this study, participants recalled how they planned a past camping
      trip in Australia (past planning task) and imagined how they would plan a future
      camping trip (future planning task), set either in a familiar (Australia) or an
      unfamiliar (Antarctica) context. Transcripts were segmented into information
      units that were coded according to semantic category (e.g., where, when,
      transport, material, actions). Results revealed a strong interaction between
      tasks and their presentation order. Starting with the past planning task
      constrained the future planning task when the context was familiar. Participants
      generated no new information when the future camping trip was set in Australia
      and completed second (after the past planning task). Conversely, starting with
      the future planning task facilitated the past planning task. Participants
      recalled more information units of their past plan when the past planning task
      was completed second (after the future planning task). These results shed new
      light on the role of scripts in past and future thinking and on how past and
      future thinking processes interact. 

PMID- 26308677
TI  - Narrative change in Gloria Films: Comparing various processes of therapeutic
      innovation.
AB  - AIMS: The present study focuses on the analysis of novelty emergence in classic
      Gloria Films with Rogers, Perls, and Ellis to understand how the same client
      formulated her own problem and if and how change occurred in those three
      sessions. METHOD: The Innovative Moments Coding System was applied to track
      innovative moments (IMs) and their themes. RESULTS: The session with Rogers
      showed more diversity in disclosed problems and themes of IMs, as well as a
      higher proportion of reflection IMs. The session with Perls demonstrated a high
      proportion of protest IMs. The session with Ellis showed less innovation than
      other sessions. The changes found were based mostly on reflection and protest IMs
      in three sessions. CONCLUSION: Narrative innovations occurred in the three single
      sessions. The type of dominant innovation is consistent with the therapeutic
      model and the IMs model. The exploration of the IMs' themes allowed a more
      precise identification of Gloria's new narrative positions and their development
      throughout those sessions.

PMID- 26308678
TI  - Developing the Scientific Infrastructure to Produce Ethnogenetically-Specific
      Personalized Medicine.

PMID- 26308676
TI  - Pericoannosin A, a Polyketide Synthase-Nonribosomal Peptide Synthetase Hybrid
      Metabolite with New Carbon Skeleton from the Endophytic Fungus Periconia sp.
AB  - Four new polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) hybrid
      metabolites, pericoannosin A (1), with an unusual hexahydro-1H-isochromen-5
      isobutylpyrrolidin-2-one skeleton, and three cytochalasans, periconiasins D-F (2
      4), were isolated from the endophytic fungus Periconia sp. F-31. Their structures
      and absolute configurations were elucidated through extensive spectroscopic
      analyses, calculated ECD, and single-crystal X-ray diffraction (Cu Kalpha). A
      possible biogenetic pathway is proposed. Compounds 1 and 4 showed anti-HIV
      activity with IC50s of 69.6 and 29.2 MUM, respectively. 

PMID- 26308679
TI  - Force Sense of the Knee Not Affected by Fatiguing the Knee Extensors and Flexors.
AB  - CONTEXT: Knee injuries commonly occur in later stages of competition, indicating
      that fatigue may influence dynamic knee stability. Force sense (FS) is a
      submodality of proprioception influenced by muscle mechanoreceptors, which, if
      negatively affected by fatigue, may result in less-effective neuromuscular
      control. OBJECTIVES: To determine the effects of peripheral fatigue on FS of the
      quadriceps and hamstrings. DESIGN: Quasi-experimental study design. PARTICIPANTS:
      20 healthy and physically active women and men (age 23.4 +/- 2.7 y, mass 69.5 +/-
      10.9 kg, height 169.7 +/- 9.4 cm). INTERVENTIONS: Fatigue was induced during a
      protocol with 2 sets of 40 repetitions, and the last set was truncated at 90
      repetitions or stopped if torque production dropped below 25% of peak torque.
      MAIN OUTCOME MEASURES: FS of the hamstrings and quadriceps was tested on separate
      days before and after 3 sets of isokinetic knee flexion and extension to fatigue
      by examining the ability to produce a target isometric torque (15% MVIC) with and
      without visual feedback (FS error). Electromyographic data of the tested
      musculature were collected to calculate and determine median frequency shift. T
      tests and Wilcoxon signed-rank tests were conducted to examine prefatigue and
      postfatigue FS error for flexion and extension. RESULTS: Despite verification of
      fatigue via torque-production decrement and shift in median frequency, no
      significant differences were observed in FS error for either knee flexion (pre
      0.54 +/- 2.28 N.m, post 0.47 +/- 1.62 N.m) or extension (pre -0.28 +/- 2.69 N.m,
      post -0.21 +/- 1.78 N.m) prefatigue compared with the postfatigue condition.
      CONCLUSIONS: Although previous research has demonstrated that peripheral fatigue
      negatively affects threshold to detect passive motion (TTDPM), it did not affect
      FS as measured in this study. The peripheral-fatigue protocol may have a greater
      effect on the mechanoreceptors responsible for TTDPM than those responsible for
      FS. Further investigation into the effects of fatigue across various modes of
      proprioception is warranted.

PMID- 26308681
TI  - Evisceration with Primary Orbital Implant in Fulminant
      Endophthalmitis/Panophthalmitis.
AB  - PURPOSE: To compare the outcome of evisceration with primary orbital implant in
      blind eyes with and without fulminant infection
      (endophthalmitis/panophthalmitis). METHODS: Retrospective nonrandomized
      comparative interventional case series. Patients with a minimum postoperative
      follow-up of 6 months were considered for inclusion. Thirty-four eyes of 34
      patients were included. Sixteen eyes were infective and 18 noninfective.
      Nonporous silicone implants were used for all cases and the main outcome measure
      was successful retention of the primary implant. Major and minor complications
      and successful prosthesis fitting were also noted. RESULTS: All except 3 cases
      were able to retain the primary implant successfully and all but 2 patients
      underwent successful prosthesis fitting. Major complications included implant
      extrusion in 3 cases (2 infective, 1 noninfective) and implant exposure in 1 case
      (noninfective). The difference in major complications between the groups was not
      statistically significant (p = 0.66, Fisher exact test). CONCLUSION: Our data
      suggest that evisceration with primary orbital implant is a feasible option in
      fulminant endophthalmitis/panophthalmitis and provides a good postoperative
      cosmetic outcome to the anophthalmic socket at an economical cost.

PMID- 26308682
TI  - Surface-Mediated in Situ Metalation of Porphyrins at the Solid-Vacuum Interface.
AB  - The investigation of porphyrin derivatives at the solid-vacuum interface has
      become a vivid research field with the prospect to tailor functional molecular
      architectures and as prototype examples to study the fundamental properties of
      porphyrin derivatives in regard to their vital role in many natural processes.
      The functional properties of the porphyrin derivatives are mainly determined by
      the central metal atom. Thus, the recent exploration of the surface-confined in
      situ metalation of porphyrins is an important step toward the realization of
      molecule-based functional devices. The corresponding metalation reaction of free
      base porphyrin derivatives can be conveniently realized in situ in ultrahigh
      vacuum by post- or predeposition of metal atoms or directly with substrate atoms
      in the so-called self-metalation. Moderate heating above room temperature (RT)
      might be necessary either to realize the transport of the metal to the porphyrin
      via diffusion or to overcome an activation barrier determined by the redox
      reaction itself. Surface science techniques like scanning tunneling microscopy
      (STM), X-ray photoelectron spectroscopy (XPS), and temperature-programmed
      desorption (TPD) are powerful tools to scrutinize the reaction and give valuable
      insights into the metalation process. For example, the completed metalation can
      be reflected in an enhanced apparent height of the corresponding porphyrin in STM
      or can be evidenced by characteristic changes in the N 1s region in XPS. These
      signatures allow monitoring of the progress of the metalation, and it was found
      that the reaction generally proceeds with very high yield. Surface diffusion of
      the coadsorbed metal atoms mediates the reaction and is crucial for the high
      yields of the corresponding reactions with pre- and postadsorbed metals. It was
      also demonstrated that the completed metalation can indeed significantly alter
      the adsorption behavior and the electronic properties and thus the functionality
      of the porphyrin molecules. These alterations can be used to monitor the kinetics
      of a particular porphyrin self-metalation reaction by STM and to estimate the
      activation barrier for that reaction based on isothermal measurements at
      different temperatures. Also TPD measurements of the H2 and D2 signals allow for
      the determination of corresponding activation energies for the metalation of free
      base porphyrins and their deuterized analogues. Gas phase DFT calculations of the
      metalation of the "bare" free base porphyrin macrocycle identify intermediate
      reaction steps with the transfer of the first hydrogen atom to the metal center
      being the main barrier to overcome. The values from these calculations are in
      fair agreement with experimentally determined ones. However, TPD based results
      indicate that exchanges of deuterium and hydrogen between the central nitrogen
      and the surface occur, which indicate an active role of the surface and challenge
      the findings from gas phase DFT. The in situ metalation of porphyrins at the
      solid-vacuum interface is established as a novel and convenient route to tailor
      functional molecular architectures. With different surface science techniques
      detailed insights into the surface-mediated metalation reaction were achieved for
      this class of prototype functional molecules. 

PMID- 26308683
TI  - Invisible Colleagues.

PMID- 26308685
TI  - Outcomes of Daytime Procedures Performed by Attending Surgeons after Night Work.
AB  - BACKGROUND: Sleep loss in attending physicians has an unclear effect on patient
      outcomes. In this study, we examined the effect of medical care provided by
      physicians after midnight on the outcomes of their scheduled elective procedures
      performed during the day. METHODS: We conducted a population-based,
      retrospective, matched-cohort study in Ontario, Canada. Patients undergoing 1 of
      12 elective daytime procedures performed by a physician who had treated patients
      from midnight to 7 a.m. were matched in a 1:1 ratio to patients undergoing the
      same procedure by the same physician on a day when the physician had not treated
      patients after midnight. Outcomes included death, readmission, complications,
      length of stay, and procedure duration. We used generalized estimating equations
      to compare outcomes between patient groups. RESULTS: We included 38,978 patients,
      treated by 1448 physicians, in the study, of whom 40.6% were treated at an
      academic center. We found no significant difference in the primary outcome
      (death, readmission, or complication) between patients who underwent a daytime
      procedure performed by a physician who had provided patient care after midnight
      and those who underwent a procedure performed by a physician who had not treated
      patients after midnight (22.2% and 22.4%, respectively; P=0.66; adjusted odds
      ratio, 0.99; 95% confidence interval, 0.95 to 1.03). We also found no significant
      difference in outcomes after stratification for academic versus nonacademic
      center, physician's age, or type of procedure. Secondary analyses revealed no
      significant difference between patient groups in length of stay or procedure
      duration. CONCLUSIONS: Overall, the risks of adverse outcomes of elective daytime
      procedures were similar whether or not the physician had provided medical
      services the previous night. (Funded by the University of Toronto Dean's Fund and
      others.).

PMID- 26308686
TI  - CLINICAL PRACTICE. Primary Care for Men Who Have Sex with Men.

PMID- 26308687
TI  - IMAGES IN CLINICAL MEDICINE. Single Bubble--Pyloric Atresia.

PMID- 26308688
TI  - CASE RECORDS of the MASSACHUSETTS GENERAL HOSPITAL. Case 27-2015. A 78-Year-Old
      Man with Hypercalcemia and Renal Failure.

PMID- 26308684
TI  - Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension.
AB  - BACKGROUND: Data on the effect of initial combination therapy with ambrisentan
      and tadalafil on long-term outcomes in patients with pulmonary arterial
      hypertension are scarce. METHODS: In this event-driven, double-blind study, we
      randomly assigned, in a 2:1:1 ratio, participants with World Health Organization
      functional class II or III symptoms of pulmonary arterial hypertension who had
      not previously received treatment to receive initial combination therapy with 10
      mg of ambrisentan plus 40 mg of tadalafil (combination-therapy group), 10 mg of
      ambrisentan plus placebo (ambrisentan-monotherapy group), or 40 mg of tadalafil
      plus placebo (tadalafil-monotherapy group), all administered once daily. The
      primary end point in a time-to-event analysis was the first event of clinical
      failure, which was defined as the first occurrence of a composite of death,
      hospitalization for worsening pulmonary arterial hypertension, disease
      progression, or unsatisfactory long-term clinical response. RESULTS: The primary
      analysis included 500 participants; 253 were assigned to the combination-therapy
      group, 126 to the ambrisentan-monotherapy group, and 121 to the tadalafil
      monotherapy group. A primary end-point event occurred in 18%, 34%, and 28% of the
      participants in these groups, respectively, and in 31% of the pooled-monotherapy
      group (the two monotherapy groups combined). The hazard ratio for the primary end
      point in the combination-therapy group versus the pooled-monotherapy group was
      0.50 (95% confidence interval [CI], 0.35 to 0.72; P<0.001). At week 24, the
      combination-therapy group had greater reductions from baseline in N-terminal pro
      brain natriuretic peptide levels than did the pooled-monotherapy group (mean
      change, -67.2% vs. -50.4%; P<0.001), as well as a higher percentage of patients
      with a satisfactory clinical response (39% vs. 29%; odds ratio, 1.56 [95% CI,
      1.05 to 2.32]; P=0.03) and a greater improvement in the 6-minute walk distance
      (median change from baseline, 48.98 m vs. 23.80 m; P<0.001). The adverse events
      that occurred more frequently in the combination-therapy group than in either
      monotherapy group included peripheral edema, headache, nasal congestion, and
      anemia. CONCLUSIONS: Among participants with pulmonary arterial hypertension who
      had not received previous treatment, initial combination therapy with ambrisentan
      and tadalafil resulted in a significantly lower risk of clinical-failure events
      than the risk with ambrisentan or tadalafil monotherapy. (Funded by Gilead
      Sciences and GlaxoSmithKline; AMBITION ClinicalTrials.gov number, NCT01178073.).

PMID- 26308689
TI  - Catheter Ablation for Persistent Atrial Fibrillation.

PMID- 26308690
TI  - Catheter Ablation for Persistent Atrial Fibrillation.

PMID- 26308691
TI  - Catheter Ablation for Persistent Atrial Fibrillation.

PMID- 26308692
TI  - Catheter Ablation for Persistent Atrial Fibrillation.

PMID- 26308693
TI  - Systemic Inflammatory Response Syndrome Criteria for Severe Sepsis.

PMID- 26308694
TI  - Systemic Inflammatory Response Syndrome Criteria for Severe Sepsis.

PMID- 26308695
TI  - Systemic Inflammatory Response Syndrome Criteria for Severe Sepsis.

PMID- 26308696
TI  - Systemic Inflammatory Response Syndrome Criteria for Severe Sepsis.

PMID- 26308697
TI  - Systemic Inflammatory Response Syndrome Criteria for Severe Sepsis.

PMID- 26308698
TI  - The Safety of the Blood Supply--Time to Raise the Bar.

PMID- 26308699
TI  - The Safety of the Blood Supply--Time to Raise the Bar.

PMID- 26308700
TI  - IMAGES IN CLINICAL MEDICINE. A Child with Gross Hematuria.

PMID- 26308701
TI  - How university students view human papillomavirus (HPV) vaccination: A cross
      sectional study in Jinan, China.
AB  - The acceptability of HPV vaccination among university students in China is not
      well understood. Our study was of cross-sectional study design. We collected a
      questionnaire about socio-demographic characteristics, knowledge of, attitude
      toward and acceptability of HPV vaccination. A total of 351 students were
      included in data analyses, among whom 47.6% were males and 70.0% aged 19-21. Only
      10.3% had previously heard of HPV and 5.4% HPV vaccine. Male and female students
      were equally likely to accept HPV vaccine (71.8 vs 69.4%, p = 0.634) and
      recommend it to sexual partners (73.1 vs 76.7%, p = 0.441). The great majority of
      students could only afford RMB 300 (USD 50) or less for HPV vaccination. HPV
      vaccination acceptance was associated with being in year-one (Adjusted odds ratio
      (AOR)  = 3.78, 95% confidence interval (CI): 2.12-6.75), being from a key
      university (AOR = 1.88, 95%CI: 1.07-3.31), having heard of HPV-related
      morbidities (AOR = 1.88, 95% CI: 1.05-3.35), being concerned about HPV-related
      morbidities (AOR = 2.23, 95% CI: 1.16-4.27) and believing the vaccine should be
      given before first sexual contact (AOR = 2.44, 95% CI: 1.38-4.29). Female
      students were more likely to anticipate a late uptake of HPV vaccination (p =
      0.002). The relatively lower levels of HPV knowledge but higher levels of vaccine
      acceptance among undergraduates highlighted the need for education on the roles
      of sexual behaviors in HPV transmission. 

PMID- 26308702
TI  - Development of an indirect ELISA based on a truncated S protein of the porcine
      epidemic diarrhea virus.
AB  - Porcine epidemic diarrhea (PED) is a highly contagious, enteric disease of swine
      caused by the porcine epidemic diarrhea virus (PEDV). To find a suitable ELISA
      method to assess the infection of PEDV and the effectiveness of vaccines, we
      developed and evaluated an indirect enzyme-linked immunosorbent assay (iELISA)
      based on a truncated recombinant spike (S) protein expressed in Escherichia coli.
      The parameters of the iELISA were optimized, and the cutoff value determined as
      0.259 by analyzing optical density (OD) values of 80 PEDV negative sera confirmed
      by western blot. Repeatability tests revealed that the coefficients of variation
      of positive sera within and between runs were both less than 10%. Cross
      reactivity assays demonstrated that iELISA was PEDV-specific. A virus
      neutralization test with sera of 7 different OD values showed a positive
      correlation between the OD values and virus neutralization. The results suggest
      this iELISA is specific, sensitive, and repeatable. Further studies should focus
      on the relationship between OD values of sera and its virus neutralization. 

PMID- 26308704
TI  - Genetic variations of the GP6 regulatory region in patients with sticky platelet
      syndrome and miscarriage.
AB  - INTRODUCTION: Thrombophilia increases the risk of venous thrombosis during
      pregnancy and may predispose to gestational vascular complications. OBJECTIVE:
      The aim of this study is to evaluate the variability of GP6 regulatory regions in
      a group of patients with platelet hyperaggregability manifested as miscarriage
      compared with control subjects. METHODS: We examined 27 female patients with
      platelet hyperaggregability and history of spontaneous abortion and 42 healthy
      women. Platelet hyperaggregability was established by light transmission
      aggregometry. We also assessed eight SNPs within the GP6 gene. RESULTS: We found
      a higher occurrence of three SNPs in patients with platelet hyperaggregability
      and history of miscarriage (rs1671152, rs1654433, rs1671215). The haplotype
      analysis showed a significant higher occurrence of two haplotypes (ACGG, CCGT).
      CONCLUSIONS: Our results support the idea that genetic variability of GP6
      regulatory regions can be associated with platelet hyperaggregability - a
      possible cause of miscarriage.

PMID- 26308703
TI  - Successful Interferon Therapy Reverses Enhanced Hepatic Progenitor Cell
      Activation in Patients with Chronic Hepatitis C.
AB  - The enhanced accumulation of hepatic progenitor cells (HPCs) is related to the
      risk of progression to hepatocellular carcinoma (HCC). Interferon (IFN) treatment
      reduces HCC risk in patients with chronic hepatitis C virus (HCV) infection.
      However, the underlying mechanisms remain unclear. The aim of this study was to
      examine the effects of IFN treatment on HPC activation in HCV patients.
      Immunohistochemical detection and computer-assisted quantitative image analyses
      of cytokeratin 7 (CK7) were performed to evaluate HPC activation in paired pre-
      and post-treatment liver biopsies from 18 HCV patients with sustained virological
      response (SVR) to IFN-based therapy and from 23 patients without SVR, as well as
      normal liver tissues obtained from surgical resection specimens of 10 patients.
      Pretreatment HCV livers showed increased CK7 immunoreactivity, compared with
      normal livers (HCV: median, 1.38%; normal: median, 0.69%, P=0.006). IFN treatment
      reduced hepatic CK7 immunoreactivity (median, 1.57% pre-IFN vs. 0.69% post-IFN,
      P=0.006) in SVR patients, but not in non-SVR patients. The development of HCC
      following IFN treatment was encountered in 3 non-SVR patients who showed high
      post-IFN treatment CK7 immunoreactivity (>4%). Successful IFN therapy can reverse
      enhanced HPC activation in HCV patients, which may contribute to the reduced risk
      of HCC development in these patients. 

PMID- 26308706
TI  - Communicating Science: The Role of Centers for Disease Control and Prevention's
      Field-Based Epidemic Intelligence Service Officers, 2009-2014.
AB  - CONTEXT: A highly skilled public health workforce is needed for responding to
      health threats, and that workforce must be able to communicate its scientific
      findings effectively. OBJECTIVE: We evaluated the scientific communication
      effectiveness of the Centers for Disease Control and Prevention's (CDC's) field
      based Epidemic Intelligence Service officers (EISOs). DESIGN: A descriptive
      analysis of all scientific information products produced and submitted for
      institutional clearance by CDC's field-based EISOs during 2009-2014. MAIN OUTCOME
      MEASURE(S): The number of abstracts, journal manuscripts, Morbidity and Mortality
      Weekly Reports (MMWRs), and other information products approved by CDC during
      2009-2014; the number of those products published; and of those published, the
      number cited in the scientific literature. RESULTS: During 2009-2014, a total of
      152 field-based EISOs produced 835 scientific information products, including 437
      abstracts, 261 manuscripts, and 103 MMWRs. The majority of scientific information
      products submitted for clearance were abstracts (52.3%), and infectious diseases
      (75.3%) constituted the majority of topics. Among the 103 MMWRs and 261
      manuscripts cleared, 88 (85%) and 199 (76%) were published, respectively, with
      the majority also infectious disease-related. The 199 published manuscripts were
      cited in the scientific literature 2415 times, and the 88 published MMWRs were
      cited 1249 times. Field-based EISOs published their work in 74 different peer
      reviewed medical and public health journals, with 54% published in journals with
      impact factors of 1 to 5. CONCLUSIONS: Field-based EISOs' publications are a
      measurable marker that reflects proficiency in epidemiology, written
      communication, and professionalism, and those publications are a direct
      reflection of EISOs' contribution to local and state health departments. Our
      study establishes a baseline for future evaluations of publication outcome of
      scientific information products by EISOs. Information released by EISOs provides
      health professionals with the scientific knowledge necessary for improving their
      practice and helps CDC achieve a broader societal, environmental, cultural, and
      economic impact.

PMID- 26308705
TI  - The Influence of Knee Pain Location on Symptoms, Functional Status, and Knee
      related Quality of Life in Older Adults With Chronic Knee Pain: Data From the
      Osteoarthritis Initiative.
AB  - OBJECTIVE: To evaluate whether knee pain location can influence symptoms,
      functional status, and knee-related quality of life in older adults with chronic
      knee pain. MATERIALS AND METHODS: A total of 2959 painful knees from the
      Osteoarthritis Initiative database were analyzed. Trained interviewers recorded
      patient-reported location of knee pain. Painful knees were divided into 3 groups
      of patellofemoral only pain, tibiofemoral only pain, and combined pain. Self
      reported knee-specific symptoms, functional status, and knee-related quality of
      life were assessed using the Knee Injury and Osteoarthritis Outcome Score.
      RESULTS: The most common knee pain pattern was tibiofemoral only pain (62%),
      followed by patellofemoral only pain (23%), and combined pain (15%). The combined
      pain pattern was associated with greater odds of reporting pain, symptoms,
      sports, or recreational activity limitations and lower knee-related quality of
      life compared with either isolated knee pain patterns, after adjusting for
      demographics and radiographic disease severity. Individual item analysis further
      revealed that patients with combined pain had greater odds of reporting
      difficulty with daily weight-bearing activities that required knee bending
      compared with tibiofemoral or patellofemoral only pain patterns. Furthermore,
      symptoms, functional status, and knee-related quality of life were comparable
      between patients with patellofemoral and tibiofemoral only pain patterns, after
      adjusting for demographics and radiographic disease severity. DISCUSSION:
      Combined patellofemoral and tibiofemoral pain is associated with poorer clinical
      presentation compared with isolated knee pain from either location. In addition,
      patellofemoral pain in isolation may be as important as tibiofemoral pain in
      causing symptoms and functional limitation in older adults with chronic knee
      pain.

PMID- 26308707
TI  - Chronic pain and the thoracic spine.
AB  - In recent years there has been an increased interest in pain neuroscience in
      physical therapy.1,2 Emerging pain neuroscience research has challenged
      prevailing models used to understand and treat pain, including the Cartesian
      model of pain and the pain gate.2-4 Focus has shifted to the brain's processing
      of a pain experience, the pain neuromatrix and more recently, cortical
      reorganisation of body maps.2,3,5,6 In turn, these emerging theories have
      catapulted new treatments, such as therapeutic neuroscience education (TNE)7-10
      and graded motor imagery (GMI),11,12 to the forefront of treating people
      suffering from persistent spinal pain. In line with their increased use, both of
      these approaches have exponentially gathered increasing evidence to support their
      use.4,10 For example, various randomised controlled trials and systematic reviews
      have shown that teaching patients more about the biology and physiology of their
      pain experience leads to positive changes in pain, pain catastrophization,
      function, physical movement and healthcare utilisation.7-10 Graded motor imagery,
      in turn, has shown increasing evidence to help pain and disability in complex
      pain states such as complex regional pain syndrome (CRPS).11,12 Most research
      using TNE and GMI has focussed on chronic low back pain (CLBP) and CRPS and none
      of these advanced pain treatments have been trialled on the thoracic spine. This
      lack of research and writings in regards to the thoracic spine is not unique to
      pain science, but also in manual therapy. There are, however, very unique pain
      neuroscience issues that skilled manual therapists may find clinically meaningful
      when treating a patient struggling with persistent thoracic pain. Utilising the
      latest understanding of pain neuroscience, three key clinical chronic thoracic
      issues will be discussed - hypersensitisation of intercostal nerves, posterior
      primary rami nerves mimicking Cloward areas and mechanical and sensitisation
      issues of the spinal dura in the thoracic spine. 

PMID- 26308708
TI  - Analysis of bone metabolism during early stage and clinical benefits of early
      intervention with alendronate in patients with systemic rheumatic diseases
      treated with high-dose glucocorticoid: Early DIagnosis and Treatment of
      OsteopoRosis in Japan (EDITOR-J) study.
AB  - We conducted a prospective multicenter study to assess early changes in the
      dynamics of bone metabolism in patients with systemic connective tissue diseases
      following commencement of high-dose glucocorticoid therapy and the benefits of
      early treatment with bisphosphonate and vitamin D analogue. The subjects of this
      randomized controlled trial were 106 female patients with systemic connective
      tissue diseases treated for the first time with glucocorticoids at doses
      equivalent to prednisolone >=20 mg/day (age >= 18 years). One week after
      initiation of glucocorticoid therapy, patients were randomly assigned to
      treatment with alfacalcidol at 1 MUg/day (n = 33), alendronate 35 mg/week (n =
      37), and alfacalcidol plus alendronate (n = 36). The primary endpoints were
      changes in lumbar spine bone density at 6 months of treatment and the frequency
      of bone fracture at 12 months. Commencement of glucocorticoid therapy was
      associated with a rapid and marked bone resorption within 1 week. The combination
      of alfacalcidol and alendronate administered after the first week of
      glucocorticoid therapy halted the pathological processes affecting bone
      metabolism, increased bone density, and reduced the incidence of bone fracture
      over a period of 12 months. Taken together, the use of the combination of
      alfacalcidol and alendronate improved bone metabolism, increased bone density,
      and significantly reduced the incidence of bone fracture during 1-year high-dose
      glucocorticoid therapy.

PMID- 26308710
TI  - Hepatitis E infection in patients with severe alcoholic hepatitis: is there a
      place for systematic screening?
AB  - BACKGROUND: One study has suggested that markers of acute hepatitis E virus (HEV)
      infection are present in 3.6% of patients with severe alcoholic hepatitis (AH).
      However, validation of these preliminary results is lacking, as well as the
      impact of HEV infection on the 6-month survival. AIMS: The aims of this study
      were to evaluate the prevalence of HEV infection markers in an external cohort of
      patients with histologically proven severe AH and to assess the impact of markers
      of acute HEV infection on the 6-month survival and the need for liver
      transplantation (LT). PATIENTS AND METHODS: Patients admitted for severe AH from
      January 2008 to June 2014 were analysed. HEV serology (IgM and IgG) was
      retrospectively performed. RESULTS: Ninety-three patients were analysed (male sex
      77.4%, age 53+/-9 years, Maddrey discriminant function 65+/-32, MELD score 24+/
      6). Six patients (6.5%) had markers of acute HEV infection (IgM+and IgG+), 11
      (11.8%) of past HEV infection (IgG+and IgM-) and 76 (81.7%) had a negative
      serology (IgM- and IgG-). Initial presentation and biological characteristics
      were not different between IgM+ and IgM- patients, except for the aspartate
      aminotransferase level (P<0.001). Markers of acute HEV infection had no impact on
      response to corticosteroids, 1-, 3- or 6-month survival, and the need for LT.
      Three patients showed symptomatic acute HEV at onset of acute AH: two were
      treated with ribavirin during the acute phase: one patient died and one patient
      underwent LT. CONCLUSION: Markers of acute HEV infection were present in 6.5% of
      patients in our cohort of cirrhotics with histologically proven severe AH,
      without any impact on short-term or long-term outcome. Whether systematic
      screening of acute HEV infection in this population should be performed remains
      an unsolved question.

PMID- 26308709
TI  - SmD1 Modulates the miRNA Pathway Independently of Its Pre-mRNA Splicing Function.
AB  - microRNAs (miRNAs) are a class of endogenous regulatory RNAs that play a key role
      in myriad biological processes. Upon transcription, primary miRNA transcripts are
      sequentially processed by Drosha and Dicer ribonucleases into ~22-24 nt miRNAs.
      Subsequently, miRNAs are incorporated into the RNA-induced silencing complexes
      (RISCs) that contain Argonaute (AGO) family proteins and guide RISC to target
      RNAs via complementary base pairing, leading to post-transcriptional gene
      silencing by a combination of translation inhibition and mRNA destabilization.
      Select pre-mRNA splicing factors have been implicated in small RNA-mediated gene
      silencing pathways in fission yeast, worms, flies and mammals, but the underlying
      molecular mechanisms are not well understood. Here, we show that SmD1, a core
      component of the Drosophila small nuclear ribonucleoprotein particle (snRNP)
      implicated in splicing, is required for miRNA biogenesis and function. SmD1
      interacts with both the microprocessor component Pasha and pri-miRNAs, and is
      indispensable for optimal miRNA biogenesis. Depletion of SmD1 impairs the
      assembly and function of the miRISC without significantly affecting the
      expression of major canonical miRNA pathway components. Moreover, SmD1 physically
      and functionally associates with components of the miRISC, including AGO1 and
      GW182. Notably, miRNA defects resulting from SmD1 silencing can be uncoupled from
      defects in pre-mRNA splicing, and the miRNA and splicing machineries are
      physically and functionally distinct entities. Finally, photoactivatable
      ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) analysis
      identifies numerous SmD1-binding events across the transcriptome and reveals
      direct SmD1-miRNA interactions. Our study suggests that SmD1 plays a direct role
      in miRNA-mediated gene silencing independently of its pre-mRNA splicing activity
      and indicates that the dual roles of splicing factors in post-transcriptional
      gene regulation may be evolutionarily widespread. 

PMID- 26308711
TI  - Clinical application of faecal calprotectin in ulcerative colitis patients.
AB  - OBJECTIVE: Faecal calprotectin (FC) is the most relevant noninvasive biomarker
      for monitoring inflammatory status, response to treatment and for predicting
      clinical relapse in ulcerative colitis (UC). The aim of this study was to
      evaluate the role of FC in predicting both clinical/endoscopic activity and
      clinical relapse in a large UC patient cohort. PATIENTS AND METHODS: A two-phase
      prospective study was carried out. In the first phase, the relationship between
      FC and clinical/endoscopic activity was evaluated. In the second phase, a cohort
      of asymptomatic patients with endoscopic mucosal healing was followed up using
      clinical and FC level determinations. RESULTS: One hundred and twenty-one UC
      patients were enrolled. The FC concentrations were directly correlated with both
      clinical and endoscopic activity (r=0.76 and 0.87, respectively, P<0.05) and were
      capable of differentiating between different degrees of endoscopic severity
      (P<0.01). An FC cut-off value of 110 MUg/g was highly predictive (95%) of
      endoscopic activity. Seventy-four patients in clinical remission with mucosal
      healing were followed up for a year or until relapse and 27% developed a clinical
      relapse. The FC concentration of nonrelapsed patients (48 MUg/g) versus relapsed
      patients (218 MUg/g) was significantly different (P<0.01). An FC cut-off value of
      193 MUg/g had an accuracy of 89% in predicting clinical relapse. High FC levels
      were associated with clinical relapse using survival analysis and multivariate
      analysis. CONCLUSION: Our data strongly support the use of FC for staging the
      activity of disease, predicting relapse and leading decision-making in a UC
      setting.

PMID- 26308712
TI  - Increased mean platelet volume is related to histologic severity of primary
      biliary cirrhosis.
AB  - AIM: To evaluate the main platelet volume (MPV) as a severity marker in patients
      with primary biliary cirrhosis (PBC). MATERIALS AND METHODS: Thirty-nine patients
      with biopsy-proven and as yet untreated PBC followed between January 2008 and
      January 2015 were included in this study. Liver biopsies were categorized as
      early stage (stage 1 and 2 according to Scheuer's histological stage) and late
      stage (Scheuer's stage 3 and 4). As part of the routine evaluation, all PBC
      patients had their full blood count and biochemistry profile determined, where
      MPV, white blood cell count, hemoglobin, platelet count, red cell distribution
      width (RDW), alanine aminotransferase, aspartate aminotransferase (AST), gamma
      glutamyl transferase, alkaline phosphatase, and total bilirubin values were
      evaluated. Both groups were compared in terms of the RDW/platelet ratio, the AST
      platelet ratio index, and the neutrophil lymphocyte ratio. RESULTS: Eighteen
      patients had early-stage disease (46.2%), whereas 21 PBC patients had late-stage
      disease (53.8%). There were no differences between groups in terms of routine
      hematological parameters (white blood cell count, platelet count, hemoglobin,
      RDW) or biochemical parameters (alanine aminotransferase, AST, gamma glutamyl
      transferase, alkaline phosphatase, total bilirubin, albumin) (P>0.05). Similarly,
      there were no differences in AST platelet ratio index, RDW/platelet ratio, or
      neutrophil lymphocyte ratio values between groups (P values 0.08, 0.19, and 0.14,
      respectively). The MPV and direct bilirubin were significantly higher in the
      advanced stage group compared with the early-stage group (11.08 vs. 9.73 fl,
      respectively, P=0.01 and 0.44 vs. 0.28 mg/dl, respectively, P=0.03). The area
      under the curve, cut-off value, sensitivity, and specificity of MPV and direct
      bilirubin for detecting advanced stage were 0.721, 10.3, 71%, and 66%,
      respectively, and 0.698, 0.23, 71%, and 66%, respectively. CONCLUSION: MPV can be
      used as a noninvasive, simple, and effective parameter in patients with PBC to
      predict histological severity of the disease.

PMID- 26308713
TI  - The CAPITAL study (CArdiovascular Prevention wIth Telecardiology in ApuLia):
      preliminary results.
AB  - BACKGROUND: The CArdiovascular Prevention wIth Telecardiology in ApuLia (CAPITAL)
      study aimed to investigate the prevalence of cardiovascular risk factors, the
      status of cardiovascular prevention, and the compliance to international
      scientific societies' guidelines on cardiovascular prevention in a Mediterranean
      region. METHODS: The CAPITAL study was based on the assessment of cardiovascular
      risk and compliance to guidelines on cardiovascular prevention, and on an
      electrocardiogram screening with remote telemedicine support performed in
      pharmacies of Apulia (Italy); the study was expected to enroll 10 000 consecutive
      patients accessing their usual pharmacy. RESULTS: In the first 1000 patients
      enrolled, 16% were smokers, 9% diabetic, 26% hypertensive, 43% overweight, and
      23% obese; 37% of the patients treated with antihypertensive drugs did not
      achieve the target levels, regardless of the number of antihypertensive drugs
      given, and 60% of subjects treated with lipid-lowering drugs did not achieve the
      target levels.Twenty-two per cent of the patients subjected to the lipid-lowering
      drugs did not check their cholesterol levels in the past 12 months, and 21% of
      those taking antihypertensive drugs did not check their blood pressure
      levels.Left ventricular hypertrophy was detected at electrocardiogram examination
      in 3.4% of the cases, and in 2.6% of the patients with unknown hypertension: 52%
      of the hypertensive patients were not checked with an electrocardiogram in the
      past 12 months, 44% of the diabetic patients, and 44% of subjects treated with
      lipid-lowering drugs. CONCLUSIONS: The awareness, therapy, and control of
      cardiovascular risk factors in a Mediterranean real-world population are
      unsatisfactory. There is a large scope of an improvement in the control of
      cardiovascular risk factors. Telemedicine support and pharmacy-based assessment
      may be helpful in implementing strategies aimed at the improvement of
      cardiovascular prevention.

PMID- 26308714
TI  - Iatrogenic left ventricular false aneurysm.
AB  - : We present a false aneurysm of ventricular left apex after mitral valve in
      valve prosthesis transapical implantation.

PMID- 26308716
TI  - Benford's Law Applies to Online Social Networks.
AB  - Benford's Law states that, in naturally occurring systems, the frequency of
      numbers' first digits is not evenly distributed. Numbers beginning with a 1 occur
      roughly 30% of the time, and are six times more common than numbers beginning
      with a 9. We show that Benford's Law applies to social and behavioral features of
      users in online social networks. Using social data from five major social
      networks (Facebook, Twitter, Google Plus, Pinterest, and LiveJournal), we show
      that the distribution of first significant digits of friend and follower counts
      for users in these systems follow Benford's Law. The same is true for the number
      of posts users make. We extend this to egocentric networks, showing that friend
      counts among the people in an individual's social network also follows the
      expected distribution. We discuss how this can be used to detect suspicious or
      fraudulent activity online and to validate datasets. 

PMID- 26308715
TI  - Effect of Silodosin, an Alpha1A-Adrenoceptor Antagonist, on Ventral Prostatic
      Hyperplasia in the Spontaneously Hypertensive Rat.
AB  - BACKGROUND: A decreased prostatic blood flow could be one of the risk factors for
      benign prostatic hyperplasia/benign prostatic enlargement. The spontaneously
      hypertensive rat (SHR) shows a chronic prostatic ischemia and hyperplastic
      morphological abnormalities in the ventral prostate. The effect of silodosin, a
      selective alpha1A-adrenoceptor antagonist, was investigated in the SHR prostate
      as a prostatic hyperplasia model focusing on prostatic blood flow. METHODS:
      Twelve-week-old male SHRs were administered perorally with silodosin (100
      MUg/kg/day) or vehicle once daily for 6 weeks. Wistar Kyoto (WKY) rats were used
      as normotensive controls and were treated with the vehicle. The effect of
      silodosin on blood pressure and prostatic blood flow were estimated and then the
      prostates were removed and weighed. The tissue levels of malondialdehyde (MDA),
      interleukin-6 (IL-6), chemokine (C-X-C motif) ligand 1/cytokine-induced
      neutrophil chemoattractant 1 (CXCL1/CINC1), tumor necrosis factor-alpha (TNF
      alpha), transforming growth factor beta 1 (TGF-beta1), basic fibroblast growth
      factor (bFGF) and alpha-smooth muscle actin (alpha-SMA) were measured. The
      histological evaluation was also performed by hematoxylin and eosin staining.
      RESULTS: There was a significant increase in blood pressure, prostate weight,
      prostate body weight ratio (PBR), tissue levels of MDA, IL-6, CXCL1/CINC1, TNF
      alpha, TGF-beta1, bFGF and alpha-SMA in the SHR compared to the WKY rat. The
      ventral prostate in the SHR showed the morphological abnormalities compared to
      the WKY rat. Prostatic blood flow was decreased in the SHR. However, treatment
      with silodosin significantly restored the decreased prostatic blood flow in the
      SHR. Moreover, silodosin normalized tissue levels of MDA, IL-6, CXCL1/CINC1, TNF
      alpha, TGF-beta1, bFGF and alpha-SMA, and it ameliorated ventral prostatic
      hyperplasia in the SHR excluding blood pressure. Silodosin decreased PBR but not
      prostate weight in the SHR. CONCLUSIONS: Silodosin can inhibit the progression of
      prostatic hyperplasia through a recovery of prostatic blood flow.

PMID- 26308718
TI  - [Not Available].

PMID- 26308717
TI  - Genetic Divergence of an Avian Endemic on the Californian Channel Islands.
AB  - The Californian Channel Islands are near-shore islands with high levels of
      endemism, but extensive habitat loss has contributed to the decline or extinction
      of several endemic taxa. A key parameter for understanding patterns of endemism
      and demography in island populations is the magnitude of inter-island dispersal.
      This paper estimates the extent of migration and genetic differentiation in three
      extant and two extinct populations of Channel Island song sparrows (Melospiza
      melodia graminea). Inter-island differentiation was substantial (G''ST: 0.14
      0.37), with San Miguel Island having the highest genetic divergence and lowest
      migration rates. Santa Rosa and Santa Cruz Island populations were less diverged
      with higher migration rates. Genetic signals of past population declines were
      detected in all of the extant populations. The Channel Island populations were
      significantly diverged from mainland populations of M. m. heermanni (G''ST: 0.30
      0.64). Ten mtDNA haplotypes were recovered across the extant and extinct Channel
      Island population samples. Two of the ten haplotypes were shared between the
      Northern and Southern Channel Islands, with one of these haplotypes being
      detected on the Californian mainland. Our results suggest that there is little
      contemporary migration between islands, consistent with early explanations of
      avian biogeography in the Channel Islands, and that song sparrow populations on
      the northern Channel Islands are demographically independent. 

PMID- 26308719
TI  - Lipid Classes and Fatty Acids in Ophryotrocha cyclops, a Dorvilleid from
      Newfoundland Aquaculture Sites.
AB  - A new opportunistic annelid (Ophryotrocha cyclops) discovered on benthic
      substrates underneath finfish aquaculture sites in Newfoundland (NL) may be
      involved in the remediation of organic wastes. At those aquaculture sites,
      bacterial mats and O. cyclops often coexist and are used as indicators of organic
      enrichment. Little is known on the trophic strategies used by these annelids,
      including whether they might consume bacteria or other aquaculture-derived
      wastes. We studied the lipid and fatty acid composition of the annelids and their
      potential food sources (degraded flocculent organic matter, fresh fish pellets
      and bacterial mats) to investigate feeding relationships in these habitats and
      compared the lipid and fatty acid composition of annelids before and after
      starvation. Fish pellets were rich in lipids, mainly terrestrially derived C18
      fatty acids (18:1omega9, 18:2omega6, 18:3omega3), while bacterial samples were
      mainly composed of omega7 fatty acids, and flocculent matter appeared to be a
      mixture of fresh and degrading fish pellets, feces and bacteria. Ophryotrocha
      cyclops did not appear to store excessive amounts of lipids (13%) but showed a
      high concentration of omega3 and omega6 fatty acids, as well as a high proportion
      of the main fatty acids contained in fresh fish pellets and bacterial mats. The
      dorvilleids and all potential food sources differed significantly in their lipid
      and fatty acid composition. Interestingly, while all food sources contained low
      proportions of 20:5omega3 and 20:2omega6, the annelids showed high concentrations
      of these two fatty acids, along with 20:4omega6. A starvation period of 13 days
      did not result in a major decrease in total lipid content; however, microscopic
      observations revealed that very few visible lipid droplets remained in the gut
      epithelium after three months of starvation. Ophryotrocha cyclops appears well
      adapted to extreme environments and may rely on lipid-rich organic matter for
      survival and dispersal in cold environments. 

PMID- 26308721
TI  - Miniaturized optogenetic neural implants: a review.
AB  - Optogenetics is an exciting new technology that allows targetable fast control
      and readout of specific neural populations in complex brain circuits. With the
      rapid development of light-sensitive microbial opsins, substantial gains in
      understanding the causal relationships between neural activity and behavior in
      both healthy and diseased brains have been achieved during the last decade.
      However, the intricate and complex interactions between different neural
      populations in mammalian brains require novel, implantable, neural interfaces
      that are capable of manipulating and probing targeted neurons at multiple sites
      and with high spatiotemporal resolution. Advanced microtechnology has offered the
      highest potential to meet these demands of optogenetic applications. In this
      paper, we review a variety of miniaturized optogenetic neural implants developed
      in recent years, based on different light sources, including lasers, laser
      diodes, and light-emitting diodes. We then summarize the specifications of these
      microimplants and their related microfabrication approaches and discuss the major
      challenges of current techniques and the vision for the future of the field. 

PMID- 26308720
TI  - Expanding the Activity of Tissue Inhibitors of Metalloproteinase (TIMP)-1 against
      Surface-Anchored Metalloproteinases by the Replacement of Its C-Terminal Domain:
      Implications for Anti-Cancer Effects.
AB  - Tissue inhibitors of metalloproteinases (TIMPs) are the endogenous inhibitors of
      the matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinases
      (ADAMs). TIMP molecules are made up of two domains: an N-terminal domain that
      associates with the catalytic cleft of the metalloproteinases (MP) and a smaller
      C-terminal domain whose role in MP association is still poorly understood. This
      work is aimed at investigating the role of the C-terminal domain in MP
      selectivity. In this study, we replaced the C-terminal domain of TIMP-1 with
      those of TIMP-2, -3 and -4 to create a series of "T1:TX" chimeras. The affinity
      of the chimeras against ADAM10, ADAM17, MMP14 and MMP19 was investigated. We can
      show that replacement of the C-terminal domain by those of other TIMPs
      dramatically increased the affinity of TIMP-1 for some MPs. Furthermore, the
      chimeras were able to suppress TNF-alpha and HB-EGF shedding in cell-based
      setting. Unlike TIMP-1, T1:TX chimeras had no growth-promoting activity. Instead,
      the chimeras were able to inhibit cell migration and development in several
      cancer cell lines. Our findings have broadened the prospect of TIMPs as cancer
      therapeutics. The approach could form the basis of a new strategy for future TIMP
      engineering. 

PMID- 26308722
TI  - What Is the Future of Sleep Medicine in the United States?

PMID- 26308723
TI  - Pirfenidone for Idiopathic Pulmonary Fibrosis: A Systematic Review and Meta
      Analysis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor prognosis.
      In the last decades pirfenidone an anti-inflammatory and anti-fibrotic agent has
      shown benefit in inhibit collagen production and has also demonstrated benefit in
      decline progression in IPF in physiological outcomes as Forced vital capacity
      (FVC), in clinical outcomes such as progression free survival (PFS) and a benefit
      in mortality but no in clinically relevant outcomes as exacerbations or worsening
      of IPF. METHODS: We conducted a systematic review to evaluate the effectiveness
      of physiological and clinical outcomes of pirfenidone compared to placebo in IPF.
      We performed a search with no language restriction. Two researchers performed
      literature search, quality assessment, data extraction and analysis. And was
      performed a summary of findings table following the GRADE approach. RESULTS: We
      included 5 RCTs (Randomized controlled trials) in analysis. The meta-analysis
      resulted in a decrease in all cause-mortality (RR 0.52 IC 0.32-0.88) and IPF
      related mortality (RR 0.32 IC 0.14-0.75); other outcomes evaluated were worsening
      of IPF (RR 0.64 IC 0.50-0.83) and acute exacerbation (RR: 0.72 IC 0.30-1.66
      respectively). Also there was a decrease in the risk of progression (RR of PFS:
      0.82 IC 0.73-0.92) compared to placebo. Conclusions: We observed significant
      differences in physiologic and clinically relevant outcomes such as reduction in
      all-cause mortality, IPF related mortality, worsening of IPF and improvement of
      PFS. So pirfenidone treatment should be considered not only for its benefits in
      pulmonary function tests but also by its clinically relevant outcomes
      [corrected].

PMID- 26308724
TI  - Characterization of CADASIL among the Han Chinese in Taiwan: Distinct Genotypic
      and Phenotypic Profiles.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) is originally featured with a strong clustering of
      mutations in NOTCH3 exons 3-6 and leukoencephalopathy with frequent anterior
      temporal pole involvement. The present study aims at characterizing the genotypic
      and phenotypic profiles of CADASIL in Taiwan. One hundred and twelve patients
      with CADASIL from 95 families of Chinese descents in Taiwan were identified by
      Sanger sequencing of exons 2 to 24 of NOTCH3. Twenty different mutations in
      NOTCH3 were uncovered, including 3 novel ones, and R544C in exon 11 was the most
      common mutation, accounting for 70.5% of the pedigrees. Haplotype analyses were
      conducted in 14 families harboring NOTCH3 R544C mutation and demonstrated a
      common haplotype linked to NOTCH3 R544C at loci D19S929 and D19S411. Comparing
      with CADASIL in most Caucasian populations, CADASIL in Taiwan has several
      distinct features, including less frequent anterior temporal involvement, older
      age at symptom onset, higher incidence of intracerebral hemorrhage, and rarer
      occurrence of migraine. Subgroup analyses revealed that the R544C mutation is
      associated with lower frequency of anterior temporal involvement, later age at
      onset and higher frequency of cognitive dysfunction. In conclusion, the present
      study broadens the spectrum of NOTCH3 mutations and provides additional insights
      for the clinical and molecular characteristics of CADASIL patients of Han-Chinese
      descents. 

PMID- 26308725
TI  - The Effects of Vibration and Muscle Fatigue on Trunk Sensorimotor Control in Low
      Back Pain Patients.
AB  - INTRODUCTION: Changes in sensorimotor function and increased trunk muscle
      fatigability have been identified in patients with chronic low back pain (cLBP).
      This study assessed the control of trunk force production in conditions with and
      without local erector spinae muscle vibration and evaluated the influence of
      muscle fatigue on trunk sensorimotor control. METHODS: Twenty non-specific cLBP
      patients and 20 healthy participants were asked to perform submaximal isometric
      trunk extension torque with and without local vibration stimulation, before and
      after a trunk extensor muscle fatigue protocol. Constant error (CE), variable
      error (VE) as well as absolute error (AE) in peak torque were computed and
      compared across conditions. Trunk extensor muscle activation during isometric
      contractions and during the fatigue protocol was measured using surface
      electromyography (sEMG). RESULTS: Force reproduction accuracy of the trunk was
      significantly lower in the patient group (CE = 9.81 +/- 2.23 Nm; AE = 18.16 +/-
      3.97 Nm) than in healthy participants (CE = 4.44 +/- 1.68 Nm; AE = 12.23 +/- 2.44
      Nm). Local erector spinae vibration induced a significant reduction in CE (4.33
      +/- 2.14 Nm) and AE (13.71 +/- 3.45 Nm) mean scores in the patient group. Healthy
      participants conversely showed a significant increase in CE (8.17 +/- 2.10 Nm)
      and AE (16.29 +/- 2.82 Nm) mean scores under vibration conditions. The fatigue
      protocol induced erector spinae muscle fatigue as illustrated by a significant
      decrease in sEMG median time-frequency slopes. Following the fatigue protocol,
      patients with cLBP showed significant decrease in sEMG root mean square activity
      at L4-5 level and responded in similar manner with and without vibration
      stimulation in regard to CE mean scores. CONCLUSIONS: Patients with cLBP have a
      less accurate force reproduction sense than healthy participants. Local muscle
      vibration led to significant trunk neuromuscular control improvements in the cLBP
      patients before and after a muscle fatigue protocol. Muscle vibration stimulation
      during motor control exercises is likely to influence motor adaptation and could
      be considered in the treatment of cLBP. Further work is needed to clearly
      identify at what levels of the sensorimotor system these gains are achievable.

PMID- 26308727
TI  - Correction: Reward-Induced Phasic Dopamine Release in the Monkey Ventral Striatum
      and Putamen.

PMID- 26308726
TI  - Identification of a Novel MYO15A Mutation in a Chinese Family with Autosomal
      Recessive Nonsyndromic Hearing Loss.
AB  - Autosomal recessive nonsyndromic hearing loss (ARNSHL) is a genetically
      heterogeneous sensorineural disorder, generally manifested with prelingual
      hearing loss and absence of other clinical manifestations. The aim of this study
      is to identify the pathogenic gene in a four-generation consanguineous Chinese
      family with ARNSHL. A novel homozygous variant, c.9316dupC (p.H3106Pfs*2), in the
      myoxin XVa gene (MYO15A) was identified by exome sequencing and Sanger
      sequencing. The homozygous MYO15A c.9316dupC variant co-segregated with the
      phenotypes in the ARNSHL family and was absent in two hundred normal controls.
      The variant was predicted to interfere with the formation of the Myosin XVa
      whirlin-Eps8 complex at the tip of stereocilia, which is indispensable for
      stereocilia elongation. Our data suggest that the homozygous MYO15A c.9316dupC
      variant might be the pathogenic mutation, and exome sequencing is a powerful
      molecular diagnostic strategy for ARNSHL, an extremely heterogeneous disorder.
      Our findings extend the mutation spectrum of the MYO15A gene and have important
      implications for genetic counseling for the family. 

PMID- 26308729
TI  - Tuneable ultra high specific surface area Mg/Al-CO3 layered double hydroxides.
AB  - We report the synthesis of tuneable ultra high specific surface area Aqueous
      Miscible Organic solvent-Layered Double Hydroxides (AMO-LDHs). We have
      investigated the effects of different solvent dispersion volumes, dispersion
      times and the number of re-dispersion cycles specific surface area of AMO-LDHs.
      In particular, the effects of acetone dispersion on two different morphology AMO
      LDHs (Mg3Al-CO3 AMO-LDH flowers and Mg3Al-CO3 AMO-LDH plates) was investigated.
      It was found that the amount of acetone used in the dispersion step process can
      significantly affect the specific surface area of Mg3Al-CO3 AMO-LDH flowers while
      the dispersion time in acetone is critical factor to obtain high specific surface
      area Mg3Al-CO3 AMO-LDH plates. Optimisation of the acetone washing steps enables
      Mg3Al-CO3 AMO-LDH to have high specific surface area up to 365 m(2) g(-1) for LDH
      flowers and 263 m(2) g(-1) for LDH plates. In addition, spray drying was found to
      be an effective and practical drying method to increase the specific surface area
      by a factor of 1.75. Our findings now form the basis of an effective general
      strategy to obtain ultrahigh specific surface area LDHs. 

PMID- 26308730
TI  - Different mechanisms at different temperatures for the ring-opening
      polymerization of lactide catalyzed by binuclear magnesium and zinc alkoxides.
AB  - Two binuclear magnesium and zinc alkoxides supported by a bis-salalen type
      dinucleating heptadentate Schiff base ligand were synthesized and fully
      characterized. The two complexes are efficient initiators for the ring-opening
      polymerization (ROP) of L-lactide, affording polymers with narrow
      polydispersities and desirable molecular weights. Interestingly, the mechanisms
      for the ROP of lactide are different at different temperatures. At a high
      temperature of 130  degrees C, a coordination-insertion mechanism is reasonable
      for the bulk melt polymerization of lactide. At a low temperature, the alkoxide
      cannot initiate the ROP reaction; however, upon the addition of external benzyl
      alcohol into the system, the ROP of lactide can smoothly proceed via an
      "activated monomer" mechanism. In addition, these complexes display slight stereo
      selectivity for the ring-opening polymerization of rac-lactide, affording
      partially isotactic polylactide in toluene with a Pm value of 0.59.

PMID- 26308731
TI  - Spontaneous Improvement of Chiari I Malformation and Syringomyelia in a Patient
      With Cystic Fibrosis: Case Report.
AB  - BACKGROUND AND IMPORTANCE: Syringomyelia is highly associated with Chiari I
      malformation, but the pathophysiologic mechanism of syrinx formation and its
      relation to downward cerebellar tonsillar displacement remains elusive. Cough,
      Valsalva maneuver, and other physiological strains transiently exacerbate the
      clinical symptoms of these conditions, exert profound effects on the flow
      dynamics across the craniospinal junction, and are thought to play an important
      role in the pathogenesis of syringomyelia. CLINICAL PRESENTATION: We report the
      case of a patient with cystic fibrosis who presented during an exacerbation of
      bronchiectasis and was found to have a Chiari I malformation with associated
      syringomyelia. Eight months later, when the patient had returned to baseline
      pulmonary status, repeat imaging showed interval improvement in both the size of
      the syrinx and descent of cerebellar tonsils. CONCLUSION: This rare case of
      spontaneous improvement of syringomyelia and Chiari I malformation attributable
      to relief from chronic cough offers interesting insight into the mechanism of
      these disorders. ABBREVIATIONS: FEV1, forced expiratory volume in 1 secondFVC,
      forced vital capacity.

PMID- 26308732
TI  - A novel Pd3O9@alpha-Al2O3 catalyst under a hydroxylated effect: high activity in
      the CO oxidation reaction.
AB  - Considering the importance of palladium-based and doped metal-oxide catalysts in
      CO oxidation, we design a new Pd3O9@alpha-Al2O3 catalyst and simulate its
      efficiency under a hydroxylated effect. The structure, electronic structure and
      oxidation activity of the hydroxylated Pd3O9@alpha-Al2O3(0001) surface are
      investigated by density functional theory. Under the O-rich growth conditions, Pd
      preferentially replaces Al. The lowest formation energy of the Pd-doped alpha
      Al2O3(0001) surface is 0.21 eV under conditions wherein the coverage of the Pd
      doped alpha-Al2O3 is 0.75 on a pre-hydroxylated surface and the water coverage is
      0.25, which leads to formation of a Pd3O9 cluster embedded in the Al2O3(0001)
      surface. The reaction mechanisms of CO oxidization have been elucidated first by
      CO adsorption and migration, second by O(v) formation with the first CO2 release,
      then by the first foreign O2 filling and CO co-adsorption, and finally by the
      second CO2 desorption and restoration of the hydroxylated Pd3O9@alpha-Al2O3(0001)
      surface. The rate-determining step is the formation of the first CO2 in the whole
      catalytic cycle. The results also indicate that the energy barrier for CO
      oxidization is obviously reduced compared to that of the undoped surface, which
      implies that the introduction of Pd can efficiently improve the oxidation
      reactivity of the alpha-Al2O3(0001) surface. Compared to the synthesized
      Ir1/FeO(x) (1.41 eV) and Pt1/FeO(x) (0.79 eV) catalysts, the reaction activation
      barrier of CO oxidation is lowered by 0.65 eV and 0.03 eV, respectively.
      Therefore, the Pd3O9@alpha-Al2O3 catalyst shows superior catalytic activity in CO
      oxidation. The present results enrich the understanding of the catalytic
      oxidation of CO by palladium-based catalysts and provide a clue for fabricating
      palladium-based catalysts with low cost and high activity.

PMID- 26308733
TI  - Cinchona alkaloid-based chiral catalysts act as highly efficient multifunctional
      organocatalysts for the asymmetric conjugate addition of malonates to
      nitroolefins.
AB  - New pentaerythritol tetrabromide-based chiral quaternary ammonium salts acting as
      organocatalysts (7a and 7b) have been prepared and used as organocatalysts for
      enantioselective Michael addition reactions between various nitroolefins and
      Michael donors (malonates) under mild reaction conditions, such as lower
      concentration of base and catalyst and room temperature, with very good chemical
      yields (up to 97%) and ee's (up to 99%). 

PMID- 26308734
TI  - Sex-Differences in the Metabolic Health of Offspring of Parents with Diabetes: A
      Record-Linkage Study.
AB  - Maternal diabetes in pregnancy affects offspring health. The impact of parental
      diabetes on offspring health is unclear. We investigated the impact of parental
      diabetes on the metabolic-health of adult-offspring who did not themselves have
      diabetes. Data from the Generation Scotland: Scottish Family Health Study, a
      population-based family cohort, were record-linked to subjects' own diabetes
      medical records. From F0-parents, we identified F1-offspring of: mothers with
      diabetes (OMD, n = 409), fathers with diabetes (OFD, n = 468), no parent with
      diabetes (ONoPD, n = 2489). Metabolic syndrome, body, biochemical measurements
      and blood-pressures were compared between F1-offspring groups by sex. A higher
      proportion of female OMD had metabolic syndrome than female OFD or ONoPD
      (P<0.0001). In female offspring, predictors of metabolic syndrome were: having a
      mother with diabetes (OR = 1.78, CI 1.03-3.07, [reference ONoPD]), body mass
      index (BMI, OR = 1.21, CI 1.13-1.30) and age (OR = 1.03, CI 1.01-1.06). In male
      offspring, predictors of metabolic syndrome were: BMI (OR = 1.18, CI 1.09-1.29)
      and percent body-fat (OR = 1.12, CI 1.05-1.19). In both sexes, OMD had higher
      blood-pressures than OFD (P<0.0001). In females, OMD had higher glucose
      (P<0.0001) and percent body-fat (P<0.0001) compared with OFD or ONoPD. OMD and
      OFD both had increased waist-measurements (P<0.0001), BMI (P<0.0001) and percent
      body-fat (P<0.0001) compared with ONoPD. Female OMD and OFD had lower HDL
      cholesterol levels (P<0.0001) than female ONoPD. Parental diabetes is associated
      with higher offspring-BMI and body-fat. In female offspring, maternal diabetes
      increased the odds of metabolic syndrome, even after adjusting for BMI. Further
      investigations are required to determine the mechanisms involved. 

PMID- 26308736
TI  - Serial ADAMTS13 measurements during initial plasma exchange therapy guide
      decisions for management of unresponsive thrombotic thrombocytopenic purpura.
AB  - BACKGROUND: The standard therapy in acquired thrombotic thrombocytopenic purpura
      (TTP) is plasma exchange. In unresponsive TTP, intensification of plasma exchange
      and immunomodulatory therapy can be initiated but it can be complicated to select
      for patients that will benefit from intensification. CASE REPORT: We describe two
      cases of newly diagnosed TTP with a complicated clinical course during initial
      treatment with plasma exchange. In one case, after an initial response to plasma
      exchange, a decrease in platelet count was observed on Day 7. The normalized
      ADAMTS13 activity guided the clinicians in the diagnosis of a concurrent heparin
      induced thrombocytopenia due to the heparin lock, used for the indwelling
      catheter. The other case with TTP clinically deteriorated early during initial
      treatment. Reevaluation on Day 5, including ADAMTS13 activity, which was
      undetectably low, supported the clinical decision to intensify the plasma
      exchange to twice daily and start with the immunomodulating agent rituximab. In
      both clinically complicated cases measurements of ADAMTS13 activity during plasma
      exchange proved to be useful in guiding treatment decisions. CONCLUSION: Serial
      measurements of ADAMTS13 activity should be considered in patients with newly
      diagnosed TTP with an unpredictable clinical course during initial therapeutic
      plasma exchange. These measurements may provide pivotal clinical insights on
      appropriate patient management.

PMID- 26308735
TI  - Pathway Analysis Based on a Genome-Wide Association Study of Polycystic Ovary
      Syndrome.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine
      disorders in women of reproductive age, and it is affected by both environmental
      and genetic factors. Although the genetic component of PCOS is evident, studies
      aiming to identify susceptibility genes have shown controversial results. This
      study conducted a pathway-based analysis using a dataset obtained through a
      genome-wide association study (GWAS) to elucidate the biological pathways that
      contribute to PCOS susceptibility and the associated genes. METHODS: We used GWAS
      data on 636,797 autosomal single nucleotide polymorphisms (SNPs) from 1,221
      individuals (432 PCOS patients and 789 controls) for analysis. A pathway analysis
      was conducted using meta-analysis gene-set enrichment of variant associations
      (MAGENTA). Top-ranking pathways or gene sets associated with PCOS were
      identified, and significant genes within the pathways were analyzed. RESULTS: The
      pathway analysis of the GWAS dataset identified significant pathways related to
      oocyte meiosis and the regulation of insulin secretion by acetylcholine and free
      fatty acids (all nominal gene-set enrichment analysis (GSEA) P-values < 0.05). In
      addition, INS, GNAQ, STXBP1, PLCB3, PLCB2, SMC3 and PLCZ1 were significant genes
      observed within the biological pathways (all gene P-values < 0.05). CONCLUSIONS:
      By applying MAGENTA pathway analysis to PCOS GWAS data, we identified significant
      pathways and candidate genes involved in PCOS. Our findings may provide new leads
      for understanding the mechanisms underlying the development of PCOS.

PMID- 26308737
TI  - Monocyte Chemoattractant Protein-Induced Protein 1 Overexpression Modulates
      Transcriptome, Including MicroRNA, in Human Neuroblastoma Cells.
AB  - The recently discovered MCPIP1 (monocyte chemoattractant protein-induced protein
      1), a multidomain protein encoded by the MCPIP1 (ZC3H12A) gene, has been
      described as a new differentiation factor, a ribonuclease, and a deubiquitination
      supporting factor. However, its role in cancer is poorly recognized. Our recent
      analysis of microarrays data showed a lack of expression of the MCPIP1 transcript
      in primary neuroblastoma, the most common extracranial solid tumor in children.
      Additionally, enforced expression of the MCPIP1 gene in BE(2)-C cells caused a
      significant decrease in neuroblastoma proliferation and viability. Aim of the
      present study was to further investigate the role of MCPIP1 in neuroblastoma,
      using expression DNA microarrays and microRNA microarrays. Transient
      transfections of BE(2)-C cells were used for overexpression of either wild type
      of MCPIP1 (MCPIP1-wt) or its RN-ase defective mutant (MCPIP1-DeltaPIN). We have
      analyzed changes of transcriptome and next, we have used qRT-PCR to verify mRNA
      levels of selected genes responding to MCPIP1 overexpression. Additionally,
      protein levels were determined for some of the selected genes. The choline
      transporter, CTL1, encoded by the SLC44A1 gene, was significantly repressed at
      the specific mRNA and protein levels and most importantly this translated into a
      decreased choline transport in MCPIP1-overexpressing cells. Then, we have found
      microRNA-3613-3p as the mostly altered in the pools of cells overexpressing the
      wild type MCPIP1. Next, we analyzed the predicted targets of the miR-3613-3p and
      validated them using qRT-PCR and western blot. These results indicate that the
      expression of miR-3613-3p might be regulated by MCPIP1 by cleavage of its
      precursor form.

PMID- 26308739
TI  - Synthesis, structure, and properties of SrC(NH)3 , a nitrogen-based carbonate
      analogue with the trinacria motif.
AB  - Strontium guanidinate, SrC(NH)3 , the first compound with a doubly deprotonated
      guanidine unit, was synthesized from strontium and guanidine in liquid ammonia
      and characterized by X-ray and neutron diffraction, IR spectroscopy, and density
      functional theory including harmonic phonon calculations. The compound
      crystallizes in the hexagonal space group P63 /m, constitutes the nitrogen
      analogue of strontium carbonate, SrCO3 , and its structure follows a layered
      motif between Sr(2+) ions and complex anions of the type C(NH)3 (2-) ; the anions
      adopt the peculiar trinacria shape. A comparison of theoretical phonons with
      experimental IR bands as well as quantum-chemical bonding analyses yield a first
      insight into bonding and packing of the formerly unknown anion in the crystal. 

PMID- 26308738
TI  - Risk Factors and Outcomes in Cats with Acquired Myasthenia Gravis (2001-2012).
AB  - BACKGROUND: Acquired myasthenia gravis (MG) in cats most commonly causes
      generalized weakness without megaesophagus and is more often associated with a
      cranial mediastinal mass, compared to dogs. HYPOTHESIS/OBJECTIVES: To extend the
      clinical findings described in the report of 2000 on MG in cats (J Am Vet Med
      Assoc 215:55-57). ANIMALS: Two hundred and thirty-five cats with MG. METHODS:
      Retrospective case study to evaluate the long-term outcome and incidence of
      spontaneous remission in myasthenic cats. Information including signalment,
      clinical presentation, presence of and type of cranial mediastinal mass,
      treatment including surgical versus medical, survival time, and outcome including
      spontaneous remissions was collected and analyzed in cats diagnosed at the
      Comparative Neuromuscular Laboratory, University of California San Diego by
      detection of acetylcholine receptor antibody titers >0.3 nmol/L by
      immunoprecipitation radioimmunosassay. RESULTS: Acquired MG in cats is associated
      with a euthanasia rate of 58%. Abyssinian and Somali cats had an increased
      incidence of MG compared to mixed breed cats or cats of other breeds. A cranial
      mediastinal mass, most commonly thymoma, was observed in 52% of the cats, which
      is higher than in the previous report. Spontaneous remission is not a
      characteristic of MG in cats. CONCLUSIONS AND CLINICAL IMPORTANCE: Myasthenia
      gravis in cats is a chronic disease associated with a high incidence of a cranial
      mediastinal mass. Spontaneous remission is not common and clinicians should warn
      owners of the necessity for long-term treatment. The clinical outcome with a
      cranial mediastinal mass did not differ between surgical or medical treatment.

PMID- 26308741
TI  - The experience error and the perils of psychopsychology.
AB  - 'The stimuli were four similar yellow objects flashing on a white background'.
      These words might not raise eyebrows when read in a research paper, but they
      should, because they probably commit the experience error (EE), in which the
      structure of our percepts is attributed to the stimulus rather than to our
      perceptual system. These words are less a description of the physical stimulus
      than of how that stimulus appears to human observers. That is problematic because
      perception is often incomplete or illusory. When we commit the EE, we confuse the
      external, physical stimulus with a response, namely our perception of it. Thus,
      we may end up relating psychological responses to stimuli solely to our
      psychological descriptions of those stimuli. This in turn may transform
      psychophysics into 'psychopsychology' and thus inadvertently leave the physical
      world out of our explanation of perception; and it may potentially demote proper
      experiments to correlational studies that lack the capacity to support inferences
      about cause and effect. Identified long ago, the EE is nearly forgotten today. We
      aim to reintroduce, clarify, and illustrate the idea more clearly, as well as to
      suggest possible preventions or cures. WIREs Cogn Sci 2014, 5:509-517. doi:
      10.1002/wcs.1302 For further resources related to this article, please visit the
      WIREs website. CONFLICT OF INTEREST: The author has declared no conflicts of
      interest for this article.

PMID- 26308740
TI  - Green processing of metal oxide core-shell nanoparticles as low-temperature
      dielectrics in organic thin-film transistors.
AB  - TiO2 , Fe3 O4, AlOx , ITO (indium tin oxide), and CeO2 nanoparticles are tailored
      to exhibit excellent dispersability in deionized water and alcohols. The latter
      provides an ecofriendly solution for processing metal oxide nanoparticles at a
      neutral pH. Water-processed dielectrics from the metal oxide nanoparticles are
      incorporated into organic thin-film transistors fabricated on rigid and flexible
      substrates. 

PMID- 26308742
TI  - Does metarepresentation make human mental time travel unique?
AB  - Recent neurological evidence suggests that rats can mentally represent novel
      spatial trajectories and then are more likely to follow these paths in the
      future. Consequently, it has been proposed that human and nonhuman mental time
      travel capacities may differ in degree rather than kind. As of yet, however,
      there is no evidence for the crucial and qualitatively distinct component of
      metarepresentation in any nonhuman animal, not even our closest great ape
      relatives. Metarepresentation allows humans to represent the relationship between
      current reality and mere representations of reality-including those of the
      future. Drawing on parallels with dreaming and mind-wandering, I outline the
      future-oriented benefits associated with uncontextualized (non
      metarepresentational) representations of past and novel events, but propose that
      further, immense benefits flowed from the addition of metarepresentational
      insight. I critique previous behavioral paradigms used to assess mental time
      travel in animals and suggest how future-oriented metarepresentation might
      possibly be demonstrated nonverbally. WIREs Cogn Sci 2014, 5:519-531. doi:
      10.1002/wcs.1308 For further resources related to this article, please visit the
      WIREs website. CONFLICT OF INTEREST: The author has declared no conflicts of
      interest for this article.

PMID- 26308743
TI  - Neuroethical issues in pharmacological cognitive enhancement.
AB  - Neuroethics is an emerging field that in general deals with the ethics of
      neuroscience and the neuroscience of ethics. In particular, it is concerned with
      the ethical issues in the translation of neuroscience to clinical practice and in
      the public domain. Numerous ethical issues arise when healthy individuals use
      pharmacological substances known as pharmacological cognitive enhancers (PCEs)
      for non-medical purposes in order to boost higher-order cognitive processes such
      as memory, attention, and executive functions. However, information regarding
      their actual use, benefits, and harms to healthy individuals is currently
      lacking. Neuroethical issues that arise from their use include the unknown side
      effects that are associated with these drugs, concerns about the modification of
      authenticity and personhood, and as a result of inequality of access to these
      drugs, the lack of distributive justice and competitive fairness that they may
      cause in society. Healthy individuals might be coerced by social institutions
      that force them to take these drugs to function better. These drugs might enable
      or hinder healthy individuals to gain better moral and self-understanding and
      autonomy. However, how these drugs might achieve this still remains speculative
      and unknown. Hence, before concrete policy decisions are made, the cognitive
      effects of these drugs should be determined. The initiation of accurate surveys
      to determine the actual usage of these drugs by healthy individuals from
      different sections of the society is proposed. In addition, robust empirical
      research need to be conducted to delineate not only whether or not these drugs
      modify complex higher-order cognitive processes but also how they might alter
      important human virtues such as empathy, moral reasoning, creativity, and
      motivation in healthy individuals. WIREs Cogn Sci 2014, 5:533-549. doi:
      10.1002/wcs.1306 For further resources related to this article, please visit the
      WIREs website. CONFLICT OF INTEREST: The author has declared no conflicts of
      interest for this article.

PMID- 26308744
TI  - Body perception, awareness, and illusions.
AB  - Perceiving a body is a phenomenal experience completely different from
      experiencing a body as one's own body. Visual presentation of bodies or body
      parts recruits several occipitotemporal regions in the brain. Are these
      activations sufficient in order to change the phenomenal status of a body in
      one's own body? In this paper, I will review consolidated experimental evidence
      showing that the feeling of owning a body is not limited to the vision of a body,
      rather it is the result of a complex interaction between interoception,
      exteroception, and pre-existing body templates. To illustrate this complex
      interplay, I will take advantage of the so-called bodily illusions, referring to
      controlled illusory generation of unusual bodily feeling. These feelings include
      having a supernumerary limb, or lacking an arm, or feeling like you do not really
      have a body, or feeling that you do not really control a certain part of your
      body, or that your body is not really yours. In the last 15 years more than 150
      empirical studies on body illusions have been published ( SOURCE: Pubmed, June
      2014). These studies, using different technologies, are largely responsible for
      contributed our current understanding of bodily self-consciousness. WIREs Cogn
      Sci 2014, 5:551-560. doi: 10.1002/wcs.1309 For further resources related to this
      article, please visit the WIREs website. CONFLICT OF INTEREST: The author has
      declared no conflicts of interest for this article.

PMID- 26308745
TI  - Punishment.
AB  - Retributivism is a deontological theory of punishment that calls for the deserved
      punishment of a guilty offender in proportion with his moral blameworthiness for
      a past offense. It is often referred to as punishment based on 'just deserts',
      and it contrasts with consequentialist theories that ground punishment in its
      potentially beneficial future consequences. Rich philosophical debate surrounds
      the appropriateness of retributivism. From a psychological perspective, the key
      question concerns whether retributivism underlies ordinary individuals' desire
      for the legal punishment of wrongdoers. Past research in social psychology has
      answered this question in the affirmative. However, much of this existing
      evidence requires a new look, because it is premised on a fundamental ambiguity.
      We review alternative evidence for the existence of retributive motives from
      lesser-known correlational studies, and from studies of the punishment of
      companies and animals. We also explore the links between retributivism and
      restorative justice-an alternative justice approach that focuses on repairing the
      harms caused by an offense. Although often cast as diametrically opposed to one
      another, retributive and restorative justice in fact share more in common than is
      often supposed. Both are premised on notions of deservingness, and their goals
      can be achieved by the same action (i.e., retributive punishment can restore
      victims). In all areas of the research we review, more work is needed to better
      understand: retributivism directed at human offenders, the commonalities and
      discontinuities between retributive and restorative justice, and how the notion
      of desert structures moral life and thought more generally. WIREs Cogn Sci 2014,
      5:561-572. doi: 10.1002/wcs.1301 For further resources related to this article,
      please visit the WIREs website. CONFLICT OF INTEREST: The authors have declared
      no conflicts of interest for this article.

PMID- 26308747
TI  - Understanding the developing sound system: interactions between sounds and words.
AB  - Over the course of the first 2 years of life, infants are learning a great deal
      about the sound system of their native language. Acquiring the sound system
      requires the infant to learn about sounds and their distributions, sound
      combinations, and prosodic information, such as syllables, rhythm, and stress.
      These aspects of the phonological system are being learned simultaneously as the
      infant experiences the language around him or her. What binds all of the
      phonological units is the context in which they occur, namely, words. In this
      review, we explore the development of phonetics and phonology by showcasing the
      interactive nature of the developing lexicon and sound system with a focus on
      perception. We first review seminal research in the foundations of phonological
      development. We then discuss early word recognition and learning followed by a
      discussion of phonological and lexical representations. We conclude by discussing
      the interactive nature of lexical and phonological representations and highlight
      some further directions for exploring the developing sound system. WIREs Cogn Sci
      2014, 5:589-602. doi: 10.1002/wcs.1307 For further resources related to this
      article, please visit the WIREs website. CONFLICT OF INTEREST: The authors have
      declared no conflicts of interest for this article.

PMID- 26308749
TI  - Comprehensive Analysis of the Therapeutic IgG4 Antibody Pembrolizumab: Hinge
      Modification Blocks Half Molecule Exchange In Vitro and In Vivo.
AB  - IgG4 antibodies are evolving as an important class of cancer immunotherapies.
      However, human IgG4 can undergo Fab arm (half molecule) exchange with other IgG4
      molecules in vivo. The hinge modification by a point mutation (S228P) prevents
      half molecule exchange of IgG4. However, the experimental confirmation is still
      expected by regulatory agencies. Here, we report for the first time the extensive
      analysis of half molecule exchange for a hinge-modified therapeutic IgG4
      molecule, pembrolizumab (Keytruda) targeting programmed death 1 (PD1) receptor
      that was approved for advanced melanoma. Studies were performed in buffer or
      human serum using multiple exchange partners including natalizumab (Tysabri) and
      human IgG4 pool. Formation of bispecific antibodies was monitored by fluorescence
      resonance energy transfer, exchange with Fc fragments, mixed mode chromatography,
      immunoassays, and liquid chromatography-mass spectrometry. The half molecule
      exchange was also examined in vivo in SCID (severe combined immunodeficiency)
      mice. Both in vitro and in vivo results indicate that the hinge modification in
      pembrolizumab prevented half molecule exchange, whereas the unmodified
      counterpart anti-PD1 wt showed active exchange activity with other IgG4
      antibodies or self-exchange activity with its own molecules. Our work, as an
      example expected for meeting regulatory requirements, contributes to establish
      without ambiguity that hinge-modified IgG4 antibodies are suitable for
      biotherapeutic applications.

PMID- 26308746
TI  - Adult hippocampal neurogenesis and its role in cognition.
AB  - Adult hippocampal neurogenesis (AHN) has intrigued neuroscientists for decades.
      Several lines of evidence show that adult-born neurons in the hippocampus are
      functionally integrated and contribute to cognitive function, in particular
      learning and memory processes. Biological properties of immature hippocampal
      neurons indicate that these cells are more easily excitable compared with mature
      neurons, and demonstrate enhanced structural plasticity. The structure in which
      adult-born hippocampal neurons are situated-the dentate gyrus-is thought to
      contribute to hippocampus function by disambiguating similar input patterns, a
      process referred to as pattern separation. Several ideas about AHN function have
      been put forward; currently there is good evidence in favor of a role for AHN in
      pattern separation. This function of AHN may be understood within a
      'representational-hierarchical' view of brain organization. WIREs Cogn Sci 2014,
      5:573-587. doi: 10.1002/wcs.1304 For further resources related to this article,
      please visit the WIREs website. CONFLICT OF INTEREST: The authors have declared
      no conflicts of interest for this article.

PMID- 26308750
TI  - Predictors of restenosis following contemporary subintimal tracking and reentry
      technique: The importance of final TIMI flow grade.
AB  - OBJECTIVES: To identify predictors of restenosis after recanalization of chronic
      total occlusions (CTOs) with the Subintimal Tracking And Reentry (STAR)
      technique. BACKGROUND: STAR is associated with high rates of restenosis but the
      associated factors are not clear. Understanding the underlying mechanisms may be
      important to improve STAR outcomes and possibly other contemporary CTO
      recanalization techniques utilizing extensive subintimal dissection and stenting.
      METHODS: We retrospectively analyzed 211 lesions that underwent a STAR procedure
      (between 2002 and 2013) with a final Thrombolysis in Myocardial Infarction (TIMI)
      flow grade 2 or 3. One-hundred and nineteen lesions that received drug eluting
      stents (DES) and underwent follow-up angiography were included in the final
      analysis. RESULTS: Of the 119 lesions treated with DES following STAR, 75
      restenoses were observed (63.0%). Utilizing multivariate analysis, TIMI flow
      grade in the recanalized artery following stent implantation at the end of the
      index procedure was the only independent predictor of restenosis. CONCLUSIONS:
      Following recanalization of a CTO with STAR, final TIMI flow predicted future
      restenosis or reocclusion. As a bailout technique, STAR resulted in a high acute
      success rate with good safety and acceptable long-term results. When poor flow is
      observed following recanalization, and prior to stent implantation, a two-step
      strategy whereby a second procedure is performed at an interval to maximize
      coronary flow at the end of the procedure may be considered with the goal to
      reduce the risk of future restenosis or total vessel occlusion following STAR.

PMID- 26308751
TI  - Moral Distress, Workplace Health, and Intrinsic Harm.
AB  - Moral distress is now being recognized as a frequent experience for many health
      care providers, and there's good evidence that it has a negative impact on the
      health care work environment. However, contemporary discussions of moral distress
      have several problems. First, they tend to rely on inadequate characterizations
      of moral distress. As a result, subsequent investigations regarding the frequency
      and consequences of moral distress often proceed without a clear understanding of
      the phenomenon being discussed, and thereby risk substantially misrepresenting
      the nature, frequency, and possible consequences of moral distress. These
      discussions also minimize the intrinsically harmful aspects of moral distress.
      This is a serious omission. Moral distress doesn't just have a negative impact on
      the health care work environment; it also directly harms the one who experiences
      it. In this paper, I claim that these problems can be addressed by first
      clarifying our understanding of moral distress, and then identifying what makes
      moral distress intrinsically harmful. I begin by identifying three common
      mistakes that characterizations of moral distress tend to make, and explaining
      why these mistakes are problematic. Next, I offer an account of moral distress
      that avoids these mistakes. Then, I defend the claim that moral distress is
      intrinsically harmful to the subject who experiences it. I conclude by explaining
      how acknowledging this aspect of moral distress should reshape our discussions
      about how best to deal with this phenomenon. 

PMID- 26308752
TI  - Effect of vitamin D supplementation on insulin resistance and glycaemic control
      in prediabetes: a systematic review and meta-analysis.
AB  - AIMS: To evaluate the effect of vitamin D on insulin resistance and glycaemic
      control in prediabetes. METHODS: A literature search was conducted of MEDLINE,
      the Cochrane Library, Cumulative Index to Nursing and Allied Health Literature
      (CINAHL), Scopus, Web of Science and www.clinicaltrials.gov, together with a
      historical search through the reference lists of relevant articles until end of
      June 2014. Studies were included if they were randomized controlled trials of
      vitamin D or vitamin D analogues in prediabetes and if they reported homeostatic
      model assessment of insulin resistance or 2-h plasma glucose after oral glucose
      tolerance test. Treatment effect was estimated according to mean difference in
      the changes from baseline of homeostatic model assessment of insulin resistance,
      2-h oral glucose tolerance test plasma glucose, fasting plasma glucose and HbA1c
      between vitamin D and control groups. Meta-analysis of eligible studies was
      performed. RESULTS: A total of 10 randomized controlled trials were included.
      Vitamin D did not significantly improve homeostatic model assessment of insulin
      resistance and 2-h oral glucose tolerance test plasma glucose: the mean
      differences were -0.06 (95% CI -0.36 to 0.24) and -0.23 mmol/l (95% CI -0.65 to
      0.19), respectively. Subgroup analysis suggested that vitamin D improved
      homeostatic model assessment of insulin resistance in a subgroup with baseline 25
      hydroxyvitamin D >= 50 nmol/l [mean difference -0.59 (95% CI -1.14 to -0.04); P =
      0.03] and improved 2-h oral glucose tolerance test plasma glucose in the subgroup
      with baseline 25-hydroxyvitamin D < 50 nmol/l [mean difference -0.68 mmol/l (95%
      CI -1.35 to -0.01); P = 0.05]. Vitamin D significantly reduced fasting plasma
      glucose and HbA1c levels. The mean differences were -0.10 mmol/l (95% CI -0.18 to
      -0.03), P = 0.006 and -1 mmol/mol (95% CI -2 to 0), P = 0.008, respectively.
      CONCLUSIONS: No beneficial effect of vitamin D in improving insulin resistance
      was identified.

PMID- 26308753
TI  - Evaluating the Heart Through the Breasts: A Feasible Strategy?

PMID- 26308754
TI  - Labeling of Enveloped Virus via Metabolic Incorporation of Azido Sugars.
AB  - Modification of an enveloped measles virus was achieved by metabolic
      incorporation of azido sugars in host cells through the protein glycosylation
      process. Based on this, the resulting measles virus particles could be modified
      with azido groups on the surface glycoproteins, which could be further labeled
      with fluorescence dyes using a strain-promoted azide-alkyne cycloaddition
      reaction. We envision this metabolic labeling approach to be applicable to a wide
      variety of enveloped viruses, allowing the facile conjugation and surface
      modification. 

PMID- 26308755
TI  - Nutrition.

PMID- 26308756
TI  - Hepatoprotective Effects of Grape Seed Procyanidin B2 in Rats With Carbon
      Tetrachloride-induced Hepatic Fibrosis.
AB  - CONTEXT: Infectious hepatitis is a serious problem affecting millions of people
      worldwide, particularly in China and other developing countries, and it is the
      major risk factor for hepatic cirrhosis. To date, the pathogenesis of hepatic
      cirrhosis is complex and unclear. Traditional Chinese medicine (TCM) has long
      been used in its treatment; however, little is known to date about the effects of
      grape seed procyanidin B2 (GSPB2) on liver fibrosis. OBJECTIVES: Using a rat
      model of carbon tetrachloride (CCl4)-induced hepatic fibrosis, the study intended
      to investigate the hepatoprotective effects of GSPB2 and to determine the
      possible pathway by which GSPB2 exerts its activities. Design * Thirty-six male,
      Sprague-Dawley rats were used in the study. Rats in a model (CCl4 only) group and
      the GSPB2 group were given CCl4 to induce hepatic fibrosis. Simultaneously,
      animals in the GSPB2 group were treated with GSPB2 by intragastric administration
      for 12 wk. In addition, the rat's Kupffer cells were cultured with CCl4 and
      GSPB2. SETTING: The study took place at the central laboratory of Qilu Hospital
      at Shandong University in Jinan, China. OUTCOME MEASURES: The following
      parameters were investigated: (1) hepatic function; (2) the liver fibrosis index
      serum hyaluronic acid (HA), laminin (LN), type 3 procollagen (PC-3), collagen 4,
      and hepatic hydroxyproline; (3) the expression in the liver of transforming
      growth factor beta-1 (TGF-beta1); (4) inflammatory cytokines in the liver and
      cell culture medium-tumor necrosis factor alpha (TNF-alpha), interleukin (IL) 1
      beta (IL-1beta), IL-6, and IL-17; (5) oxidative stress markers in the liver and
      cell culture medium-malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-OHdG),
      total superoxide dismutase (T-SOD), and total antioxidant capacity (T-AOC); and
      (6) levels of angiotensin 2 (Ang 2) in the liver. RESULTS: The CCl4 induced (1)
      significant hepatic-function damage; (2) elevated levels of the measures of the
      liver fibrosis index, TGF-beta1, inflammatory cytokines, MDA, and 8-OHdG; (3) a
      reduction in the activities of T-SOD and T-AOC; and (4) no effect on the level of
      expression of hepatic Ang 2. GSPB2 treatment partially reversed the changes
      induced by CCl4. The cell culture also showed that CCl4 elevated the levels of
      inflammatory cytokines and MDA in the Kupffer cell culture medium, whereas it
      reduced the activities of T-SOD and T-AOC in the medium. GSPB2 treatment
      partially reversed the changes induced by CCl4. CONCLUSIONS: GSPB2 had
      hepatoprotective effects on CCl4-induced hepatic fibrosis in Sprague-Dawley rats
      and inhibited the inflammatory response and oxidative stress in vivo and in
      vitro.

PMID- 26308757
TI  - Zinc Supplementation Alone Is Effective for Partial Amelioration of Methotrexate
      induced Intestinal Damage.
AB  - CONTEXT: Chemotherapeutic agents such as methotrexate (MTX) are commonly used in
      the treatment of cancer. MTX is an antimetabolite and antifolate drug that
      targets folate production in rapidly dividing intestinal cells during
      deoxyribonucleic acid/ribonucleic acid (DNA/RNA) synthesis, thus indiscriminately
      diminishing enterocyte numbers and disrupting brush-border enzyme activities. The
      resultant damage leads to a debilitating condition known as intestinal mucositis.
      New treatment strategies need to be developed for mucositis, as currently no
      effective treatment exists. OBJECTIVES: The efficacy of zinc in combination with
      the probiotic Streptococcus salivarius subsp thermophilus (TH-4) to ameliorate
      MTX-induced mucositis was investigated. DESIGN: C57BL/6 mice were randomly
      assigned to 5 groups: (1) negative control group-saline + saline (SS group); (2)
      MTX-treated control group-saline + MTX (SM group); (3) MTX-treated intervention
      group-zinc + TH-4 probiotic + MTX (ZPM group); (4) MTX-treated intervention group
      zinc + MTX (ZM group); and (5) MTX-treated intervention group-TH-4 probiotic +
      MTX (PM group). The mice were gavaged daily from days 1-16 with their respective
      treatments. From days 6-8, a total of 3 consecutive, daily subcutaneous
      injections of MTX were used to induce mucositis in the 4 MTX-treated intervention
      groups, with saline used for the negative controls. SETTING: The study was
      conducted in the gastroenterology unit at the Women's and Children's Health
      Network, North Adelaide, SA, Australia. OUTCOME MEASURES: Mice were sacrificed on
      days 10, 13, and 16. Measurements included body weight, the disease activity
      index, small-intestine (SI) length and weight, villus height, crypt depth, and
      mucosal thickness. Also, gut tissues were collected for histological assessments,
      evaluation of myeloperoxidase (MPO) activity, and analysis of metallothionein
      (MT) levels. RESULTS: On days 10 and 13, the treatments received by the ZPM and
      ZM groups resulted in significantly less jejunal damage (P < .05) compared with
      the MTX-treated controls (SM) and the PM groups. Zinc treatments in the ZM group
      induced a 3-fold increase in MT levels, resulting in a significant difference
      between that group and the SM group (P < .001). The treatments also led to MPO
      activity that was 31% lower on day 10 compared with the SM and PM groups (P < .01
      for each comparison). Mice in the ZM and the ZPM groups showed increased villus
      height (P < .05) on day 10 compared with the SM and PM groups. Similarly, mucosal
      thickness was significantly greater in the ZPM and ZM groups on day 10 compared
      with the SM and PM groups, by 36% (P = .014) and 34% (P = .002), respectively. On
      day 16, after treatment with zinc in the ZM and ZPM groups, SI weight was 24%
      lower for the ZM group and 26% lower for the ZPM group compared with the SM group
      (both P < .001). Crypt depth was increased in the PM group at day 10, resulting
      in a crypt depth that was 30% greater than that of the SM group (P = .002).
      CONCLUSION: Zinc supplementation alone may be an effective treatment strategy for
      MTX-induced mucositis, possibly by inducing MT directly.

PMID- 26308758
TI  - Phytomedicine-based and Quadruple Therapies in Helicobacter pylori Infection: A
      Comparative, Randomized Trial.
AB  - CONTEXT: Helicobacter pylori (H pylori) is strongly associated with the
      development of gastritis, duodenal and gastric ulcers, gastric mucosa-associated
      lymphoid tissue (MALT) lymphomas and gastric carcinoma. Emerging antibiotic
      resistance and patients' poor compliance with modern therapies have resulted in
      increasing eradication failure. OBJECTIVES: The current trial was conducted to
      evaluate the efficacy of current quadruple and phytomedicine-based therapies for
      the eradication of H pylori infection and relief of its associated symptoms in
      Pakistan. DESIGN: The study was a randomized, controlled, multicenter clinical
      trial. Setting * The study was conducted in high-risk areas of Pakistan,
      including at Shifa-Ul-Mulk Memorial Hospital in Karachi, at Bahawalpur Victoria
      Hospital in Bahawalpur, and at Nawaz Salik Hospital in Rawalpindi. PARTICIPANTS:
      The study enrolled 210 patients who tested positive for H pylori, 118 males and
      92 females. INTERVENTION: Participants were divided into 2 groups according to
      treatment regimens. One group of participants received quadruple therapy-20 mg of
      omeprazole, 1g of amoxicillin, 500 mg of metronidazole, and 400 mg of bismuth
      compound-that was prescribed for 7 d, and another group received an alternate,
      phytomedicine-based, quadruple formulation-500 mg of Pylorex Plus-that was
      prescribed for 15 d. OUTCOME MEASURES: The eradication rate for H pylori was the
      primary outcome measure. Eradication was considered to be achieved on the basis
      of a negative C-urea breath test (UBT) and a negative stool antigen test for H
      pylori (HpSAg) at 4 wk after the end of treatment. The secondary outcome measure
      was the improvement in the clinical features as assessed by dyspepsia scores.
      RESULTS: In an intention-to-treat (ITT) analysis, the study found that H pylori
      was eradicated in 56 of the 90 participants in the quadruple therapy group who
      completed the study (62.2%) and in 48 of the 86 participants in the Pylorex Plus
      group who completed the study (55.8%). Therefore, Pylorex Plus had an eradication
      rate comparable with quadruple therapy. However, Pylorex Plus had significantly
      reduced gastrointestinal (GI) symptoms at the second wk and at 1 mo after
      treatment, both for participants in whom H pylori was eradicated and for those in
      whom it was not eradicated. The quadruple therapy group also showed reduced GI
      symptoms at the second wk and at 1 mo after treatment, but that result occurred
      only for those participants in whom H pylori was eradicated, and no significant
      improvement was observed for participants in whom it was not eradicated.
      CONCLUSIONS: Current quadruple and alternate therapies yielded poor eradication
      rates (<70%), but the latter produced marked symptomatic improvement, both for
      participants in whom H pylori was eradicated and for those in whom it was not
      eradicated, pointing out its potential use with patients with functional
      dyspepsia (FD) who are both positive and negative for H pylori.

PMID- 26308759
TI  - Red Yeast Rice Plus Berberine: Practical Strategy for Promoting Vascular and
      Metabolic Health.
AB  - Lovastatin, the progenitor of the statin family, is in fact a naturally occurring
      compound produced by the yeast Monascus purpureus. Red yeast rice (RYR), a
      traditional Chinese food made by fermenting rice with M purpureus, is an herbal
      medicine that has been used for 1200 y as a therapy for problems related to
      circulation and digestion. RYR contains a range of compounds known as monacolins,
      of which monacolin K-renamed lovastatin by pharmaceutical researchers-was found
      to be the most potent inhibitor of cholesterol synthesis. Standardized extracts
      of RYR, providing 10 mg of monacolins daily, have been shown to lower elevated
      low-density lipoprotein (LDL) cholesterol by approximately 20%. In a large
      secondary prevention trial in China, RYR was found to be markedly protective with
      respect to cardiovascular events and total mortality. Yet RYR very rarely induces
      the myopathy and hepatic damage commonly seen with prescription statin therapy.
      The Chinese herbal compound berberine, used to treat diabetes and congestive
      heart failure in China, has been shown to increase hepatic expression of LDL
      receptors and, hence, to lower LDL cholesterol, by extending the half-life of LDL
      receptor messenger ribonucleic acid (mRNA). This effect is complementary to the
      increased transcription of this mRNA promoted by statin therapy. Because
      berberine is well tolerated aside from transient gastrointestinal (GI) upset in
      some people and, in particular, has not been reported to cause myopathy or
      hepatic damage, the combination of RYR and berberine may have the potential to
      achieve reductions in LDL cholesterol comparable with those achieved with
      prescription statin therapy, but without the associated risks such as muscle
      damage and diabetes. Moreover, berberine, via its ability to activate adenosine
      monophosphate-activated kinase (AMPK), which it shares with the drug metformin,
      can lower triglycerides, improve metabolic syndrome, aid glycemic control in
      diabetics, and act directly on the vasculature to promote vascular health. It may
      also have the potential to reduce risk for various cancers, osteoporosis,
      osteoarthritis, nonalcoholic fatty-liver disease, and neurodegenerative
      disorders, although such predictions are highly speculative. Whereas statin
      therapy modestly increases risk for type 2 diabetes, berberine likely has the
      opposite effect. These considerations suggest that combined administration of RYR
      and berberine may provide a broader range of health protection than is afforded
      by prescription statin therapy, with lower risks for serious adverse effects
      compared with statins. Randomized, controlled trials (RCTs) assessing the effect
      of optimal intakes of RYR and berberine on serum lipids and other vascular risk
      factors are needed. 

PMID- 26308760
TI  - An Ethanol Extract of Hawaiian Turmeric: Extensive In Vitro Anticancer Activity
      Against Human Colon Cancer Cells.
AB  - CONTEXT: Turmeric (Curcuma longa) is a food spice and colorant reported to be
      beneficial for human health. Curcumin (diferuloylmethane) is the major ingredient
      in turmeric, and existing data suggest that the spice, in combination with
      chemotherapy, provides a superior strategy for treatment of gastrointestinal
      cancer. However, despite its significant effects, curcumin suffers from poor
      bioavailability, due to poor absorption in the body. OBJECTIVE: The research team
      intended to evaluate a liquid extract of turmeric roots (TEx) that the team had
      formulated for its in vitro, anticancer activity against several human,
      colorectal cancer cell lines. DESIGN: The research team performed in vitro
      studies evaluating the anticancer efficacy via short and long-term assays and
      also evaluated invasion using Matrigel (Corning Life Sciences, Tewksbury, MA,
      USA). Further, in vitro anticancer activity of TEx was tested against 3-D
      cultures of HCT166 spheroids, which were subsequently analyzed by flow cytometry.
      SETTING: ADNA, Inc, Columbus, OH, USA; Foundation for Biomedical Research of the
      Academy of Athens, Athens, Greece; and Laboratory of Pharmacology, Faculty of
      Medicine, University of Thessaly, Larissa, Greece. INTERVENTION: The study used 4
      human cell lines of colorectal cancer-HT29, HCT15, DLD1, and HCT116-and 2 breast
      cancer cell lines-SW480 and MDA-MB231. For a short-term assay, the extract was
      dissolved into culture mediums of HT29, HCT15, DLD1, HCT116, and SW480 at four 10
      fold dilutions (100 to 0.1 MUg/mL). For a long-term assay, TEx was added to the
      cultures of the same cell lines at 3 dilutions-20, 10, and 5 MUg/mL. For an
      invasion assay, 100 uL per well of Matrigel was added and allowed to polymerize
      prior seeding of the MDA-MB231 cells. For cultures treated with the TEx, the TEx
      was mixed with the cell suspension prior to the seeding step. For the spheroid
      testing, the TEx was added to HCT116 cells either at the beginning of an
      experiment (ie, before the addition of the cancer cells), which was a
      chemopreventive approach, or 48 h later, on the addition of cells to the wells to
      allow the generation of spheroids, which was a chemotherapeutic approach. OUTCOME
      MEASURES: The in vitro activities of TEx were evaluated using a 48-h-incubation,
      short-term assay and a 2-wk, long-term (clonogenic) assay. To analyze the anti
      invasive activity of the extract, images for the Matrigel invasion assay were
      taken with a camera at the 24-h time point. The in vitro, anticancer activity of
      TEx was also tested against 3-D cultures of HCT116 spheroids that were
      subsequently analyzed using flow cytometry. RESULTS: TEx had potently inhibited
      the growth of all human colon cancer cell lines tested in a dose- and time
      dependent manner. TEx inhibited the formation of HCT116 spheroids when the cells
      were incubated with the extract. The extract also disrupted the formation of
      tubules formed by MDA-MB231 cells grown on Matrigel at concentrations that did
      not affect the overall viability of the cells, indicating a potent anti-invasive
      activity. CONCLUSIONS: These data suggest a potential therapeutic activity for
      TEx against human colon cancer, most likely due to the enhanced bioavailability
      of the turmeric.

PMID- 26308761
TI  - Preclinical Studies Suggest Complex Nutraceutical Strategies May Have Potential
      for Preventing and Managing Sepsis.
AB  - An analysis of signaling mechanisms triggered by toll receptor 4 (TLR4) in
      macrophages, as well as of pertinent cell-culture and rodent studies, suggests
      that various nutraceuticals may have clinical potential for preventing and
      treating Gram-negative sepsis. Endotoxin activation of TLR4 results in induction
      of nitric oxide synthase (iNOS); cyclooxygenase 2 (COX-2); tissue factor (TF);
      and a range of proinflammatory cytokines, such as tumor necrosis factor alpha
      (TNF-alpha), interleukin-1 beta (IL-1beta), and interleukin 6 (IL-6), that
      collaborate to generate the clinical picture of sepsis. Upstream activation of
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase contributes
      importantly to those effects by inducing superoxide production that promotes
      activation of p38 mitogen-activated protein (MAP) kinase and nuclear factor (NF)
      kappaBeta. Bilirubin generated intracellularly by activation of heme oxygenase 1
      (HO-1) functions to provide feedback inhibition of NAPDH-oxidase complexes.
      Exogenous bilirubin, or its precursor, biliverdin, is protective in rodent models
      of sepsis. One nutraceutical, phycocyanobilin (PhyCB), is a biliverdin derivative
      that functions as a light-gathering chromophore in cyanobacteria such as
      spirulina and can be converted intracellularly to a compound structurally
      homologous to bilirubin that likewise inhibits NADPH-oxidase complexes. In rodent
      studies, administration of phycocyanin, to which PhyCB is covalently attached,
      has likewise been shown to be protective in rodent models of sepsis. Other
      nutraceuticals provide benefits in counteracting the effects of TLR4. Phase 2
      inductive nutraceuticals, such as lipoic acid, have the potential to induce HO-1
      activity in macrophages, promoting bilirubin production. They may also antagonize
      the upregulatory impact of reactive oxygen species (ROS) on macrophage signaling
      by boosting glutathione synthesis. Another nutraceutical, glycine, helps counter
      the TLR4-triggered calcium influx that occurs through voltage-sensitive calcium
      channels and contributes to NADPH-oxidase activation, and, via activation of
      Ca+2/calmodulin-dependent kinase 2, also promotes induction of proinflammatory
      cytokines and cyclo-oxygenase 2 (COX-2). Elevations of serum glycine that are
      achievable through supplementation can block that calcium influx by activating
      membrane chloride channels in macrophages, inducing membrane hyperpolarization.
      Use of high-dose folate, another nutraceutical, has been shown to antagonize
      activation of endotoxin-mediated macrophages in cell cultures and in rodents.
      That result likely reflects the versatile, radical-scavenging activity of reduced
      intracellular folates, which in particular scavenge radicals derived from
      peroxynitrite, a key mediator of tissue damage in sepsis. Activators of adenosine
      monophosphate (AMP)-activated kinase (AMPK), such as the drug metformin or the
      nutraceutical berberine, have been shown to antagonize TLR4-mediated activation
      of extracellular-signal-regulated kinase1/2 (ERK1/2), which contributes to the
      induction of TF and TNF-alpha. In rodent models of sepsis, lipoic acid, glycine,
      high-dose folate, metformin, berberine, and phycocyanin have all shown protective
      utility, yet none of those substances has been evaluated clinically in that
      regard. Because those agents are all well tolerated individually, complex
      nutraceuticals featuring several of those agents can be envisioned as possibly
      aiding prevention and control of sepsis. Clinical evaluation of such a strategy
      should be a high priority. That approach may also have the potential for aiding
      survival in Ebola infection, the lethality of which is mediated by mechanisms
      quite analogous to those involved in sepsis. 

PMID- 26308762
TI  - Radioprotectant and Cytotoxic Effects of Spirulina in Relapsed Verrucous Vulvar
      Cancer: A Case Report.
AB  - CONTEXT: The treatment of relapsed verrucous vulvar cancer (VVC) is difficult.
      When vulvar cancer relapses, the treatment response is low for second-line
      treatments. Conversely, toxicity is high. Therefore, scientists need to identify
      different treatment methods. OBJECTIVES: The case study was intended to examine
      the benefits of combining treatment with microalgae and metronidazole with
      radiotherapy to increase the response to treatment. SETTING: The study took place
      in the Department of Radiation Oncology at Bezmialem Vakif University, in
      Istanbul, Turkey. PARTICIPANT: The case study involved an 81-y-old female patient
      whose vulvar tumor was excised and who came to the research team's radiation
      oncology service for postoperative radiation. She had 2 comorbid disorders:
      Alzheimer's disease and cardiovascular disease. INTERVENTION: A relapse had
      occurred in the 15-d postoperative period. Because of the patient's age and
      comorbid disorders, the research team decided to treat the new tumor only with
      concurrent radiochemotherapy and a weekly dose of cisplatin that contained
      chemoradiotherapy, for a total of 25 mg. At the 52.2 Gy dose level, grade 3
      radiation skin toxicity occurred in the radiated area, although the research team
      had obtained an 80% response to the radiochemotherapy. The treatment was
      interrupted because of toxicity but also due to a deterioration in the patient's
      general health. Progression of the tumor continued, and the tumor's diameter
      increased to 7 cm after a 4-mo period. The research team then initiated
      radiotherapy again, combining it with spirulina in a 750 mg/dose at 2 doses/d and
      metronidazole in a 500 mg/dose at 3 doses/d, to decrease radiation toxicity and
      increase radiosensitivity. Radiotherapy was applied at 200 cGy per fraction with
      a total dose of 2400 cGy, with only 1 anterior local-tumor field. RESULTS: The
      patient showed a complete response to radiotherapy, and the tumor disappeared at
      the 2400 cGy radiation dose. No toxicity occurred related to the skin or the
      woman's general health. Her Karnofsky performance score increased to 90% from
      50%, which was the initial score of the second treatment.

PMID- 26308763
TI  - Gerard E. Mullin, MD: The Influence of the Gut-Brain Axis on Health.

PMID- 26308764
TI  - Jon Kaiser, MD: Supporting Mitochondrial Health With Nutrient Therapy.

PMID- 26308765
TI  - America's Cannabis Experiment.

PMID- 26308767
TI  - Contrast-Enhanced X-ray Detection of Microcalcifications in Radiographically
      Dense Mammary Tissue Using Targeted Gold Nanoparticles.
AB  - Breast density reduces the accuracy of mammography, motivating methods to improve
      sensitivity and specificity for detecting abnormalities within dense breast
      tissue, but preclinical animal models are lacking. Therefore, the objectives of
      this study were to investigate a murine model of radiographically dense mammary
      tissue and contrast-enhanced X-ray detection of microcalcifications in dense
      mammary tissue by targeted delivery of bisphosphonate-functionalized gold
      nanoparticles (BP-Au NPs). Mammary glands (MGs) in the mouse mammary tumor virus 
      polyomavirus middle T antigen (MMTV-PyMT or PyMT) model exhibited greater
      radiographic density with age and compared with strain- and age-matched wild-type
      (WT) controls at 6-10 weeks of age. The greater radiographic density of MGs in
      PyMT mice obscured radiographic detection of microcalcifications that were
      otherwise detectable in MGs of WT mice. However, BP-Au NPs provided enhanced
      contrast for the detection of microcalcifications in both radiographically dense
      (PyMT) and WT mammary tissues as measured by computed tomography after
      intramammary delivery. BP-Au NPs targeted microcalcifications to enhance X-ray
      contrast with surrounding mammary tissue, which resulted in improved sensitivity
      and specificity for detection in radiographically dense mammary tissues. 

PMID- 26308766
TI  - Allergic reactions and antiasparaginase antibodies in children with high-risk
      acute lymphoblastic leukemia: A children's oncology group report.
AB  - BACKGROUND: The objectives of this study were to assess the incidence of clinical
      allergy and end-induction antiasparaginase (anti-ASNase) antibodies in children
      with high-risk acute lymphoblastic leukemia treated with pegylated (PEG)
      Escherichia coli ASNase and to determine whether they carry any prognostic
      significance. METHODS: Of 2057 eligible patients, 1155 were allocated to
      augmented arms in which PEG ASNase replaced native ASNase postinduction. Erwinia
      chrysanthemi (Erwinia) ASNase could be used to replace native ASNase after
      allergy, if available. Allergy and survival data were complete for 990 patients.
      End-induction antibody titers were available for 600 patients. RESULTS: During
      the consolidation phase, 289 of 990 patients (29.2%) had an allergic reaction.
      There were fewer allergic reactions to Erwinia ASNase than to native ASNase (odds
      ratio, 4.33; P < .0001) or PEG ASNase (odds ratio, 3.08; P < .0001) only during
      phase 1 of interim maintenance. There was no significant difference in 5-year
      event-free survival (EFS) between patients who received PEG ASNase throughout the
      entire study postinduction versus those who developed an allergic reaction to PEG
      ASNase during consolidation phase and subsequently received Erwinia ASNase (80.8%
      +/- 2.8% and 81.6% +/- 3.8%, respectively; P = .66). Patients who had positive
      antibody titers postinduction were more likely to have an allergic reaction to
      PEG ASNase (odds ratio, 2.4; P < .001). The 5-year EFS rate between patients who
      had negative versus positive antibody titers (80% +/- 2.6% and 77.7% +/- 4.3%,
      respectively; P = .68) and between patients who did not receive any ASNase
      postconsolidation and those who received PEG ASNase throughout the study (P =
      .22) were significantly different. CONCLUSIONS: The current results demonstrate
      differences in the incidence rates of toxicity between ASNase preparations but
      not in EFS. The presence of anti-ASNase antibodies did not affect EFS.

PMID- 26308768
TI  - Macrocarpal-like Compounds from Eugenia umbelliflora Fruits and Their
      Antibacterial Activity.
AB  - Certain members of the genus Eugenia are used as foods. One of these species is
      Eugenia umbelliflora, which is used for its fruits. The aim of the study was to
      isolate the constituents of the CH2Cl2 fraction obtained from E. umbelliflora O.
      Berg (Myrtaceae) and also to evaluate its antimicrobial properties. Two new
      meroterpenoids, eugenial C (3) and eugenial D (4) were isolated from the unripe
      fruits of E. umbelliflora and their structures established mainly by extensive
      NMR spectroscopy. In previous studies, the CH2Cl2 extract showed significant
      antibacterial activity, which can be attributed to meroterpenoids isolated in
      this study. The compounds eugenials C and D exhibited potent activity against
      Bacillus subtilis and Staphylococcus aureus and different strains of MRSA and
      activity similar to those of the antibiotics used in antimicrobial therapies. 

PMID- 26308770
TI  - Common genetic variants in 11q13.3 and 9q22.33 are associated with molecular
      subgroups of multiple myeloma.

PMID- 26308769
TI  - Primary testicular diffuse large B-cell lymphoma displays distinct clinical and
      biological features for treatment failure in rituximab era: a report from the
      International PTL Consortium.
AB  - Primary testicular diffuse large B-cell lymphoma (PT-DLBCL) is a unique subtype
      of DLBCL. The impact of rituximab on survival and patterns of treatment failure
      in PT-DLBCL patient remain controversial. We analyzed the clinical and biological
      feature of 280 PT-DLBCL cases, 64% of which were treated with rituximab
      containing regimens. Although most (95%) patients achieved complete remission, a
      continuous risk of relapse was observed. Rituximab significantly reduced the
      cumulative risk of relapse (P=0.022) and improved both progression-free survival
      (PFS, P=0.012) and overall survival (OS, P=0.027) of PT-DLBCL patients (5-year
      PFS, 56% vs 36%; 5-year OS, 68% vs 48%). Central nervous system and contralateral
      testis were the most common sites of relapse, but other extranodal and nodal
      sites of relapse were also observed. Most cases of PT-DLBCL had a non-germinal
      center B-cell like (84%) immunophenotype and an activated B-cell like (86%) gene
      expression profile (GEP) subtype. The distinctive GEP signature of primary
      testicular lymphoma was relevant to tumor cell proliferation, dysregulated
      expression of adhesion molecules and immune response, likely accounting for the
      poor outcome. Accordingly, forkhead box P1 transcription factor (FOXP1) and T
      cell leukemia/lymphoma 1 (TCL1) oncogenic activation were confirmed and predicted
      a significant trend of poor survival. This study provides valuable observations
      for better understanding of both clinical and biological features in PT-DLBCL
      patients. 

PMID- 26308772
TI  - Effect of the type of treatment facility on the outcome of acute myeloid leukemia
      in adolescents and young adults.

PMID- 26308773
TI  - Axial Ligand Coordination to the C-H Amination Catalyst Rh2(esp)2: A Structural
      and Spectroscopic Study.
AB  - The compound Rh2(esp)2 (esp = alpha,alpha,alpha',alpha'-tetramethyl-1,3
      benzenediproponoate) is the most generally effective catalyst for nitrenoid
      amination of C-H bonds. However, much of its fundamental coordination chemistry
      is unknown. In this work, we study the effects of axial ligand coordination to
      the catalyst Rh2(esp)2. We report here crystal structures, cyclic voltammetry, UV
      vis, IR, Raman, and (1)H NMR spectra for the complexes Rh2(esp)2L2 where L =
      pyridine, 3-picoline, 2,6-lutidine, acetonitrile, and methanol. The compounds all
      show well-defined pi* -> sigma* electronic transitions in the 16500 to 20500 cm(
      1) range, and Rh-Rh stretching vibrations in the range from 304 to 322 cm(-1).
      Taking these data into account we find that the strength of axial ligand binding
      to Rh2(esp)2 increases in the series CH3OH ~ 2,6-lutidine < CH3CN < 3
      methylpyridine ~ pyridine. Quasi-reversible Rh2(4+/5+) redox waves are only
      obtained when either acetonitrile or no axial ligand is present. In the presence
      of pyridines, irreversible oxidation waves are observed, suggesting that these
      ligands destabilize the Rh2 complex under oxidative conditions. 

PMID- 26308771
TI  - NOX4-driven ROS formation mediates PTP inactivation and cell transformation in
      FLT3ITD-positive AML cells.
AB  - Activating mutations of FMS-like tyrosine kinase 3 (FLT3), notably internal
      tandem duplications (ITDs), are associated with a grave prognosis in acute
      myeloid leukemia (AML). Transforming FLT3ITD signal transduction causes formation
      of reactive oxygen species (ROS) and inactivation of the protein-tyrosine
      phosphatase (PTP) DEP-1/PTPRJ, a negative regulator of FLT3 signaling. Here we
      addressed the underlying mechanisms and biological consequences. NADPH oxidase 4
      (NOX4) messenger RNA and protein expression was found to be elevated in FLT3ITD
      positive cells and to depend on FLT3ITD signaling and STAT5-mediated activation
      of the NOX4 promoter. NOX4 knockdown reduced ROS levels, restored DEP-1 PTP
      activity and attenuated FLT3ITD-driven transformation. Moreover, Nox4 knockout
      (Nox4(-/-)) murine hematopoietic progenitor cells were refractory to FLT3ITD
      mediated transformation in vitro. Development of a myeloproliferative-like
      disease (MPD) caused by FLT3ITD-transformed 32D cells in C3H/HeJ mice, and of a
      leukemia-like disease in mice transplanted with MLL-AF9/ FLT3ITD-transformed
      murine hematopoietic stem cells were strongly attenuated by NOX4 downregulation.
      NOX4-targeting compounds were found to counteract proliferation of FLT3ITD
      positive AML blasts and MPD development in mice. These findings reveal a
      previously unrecognized mechanism of oncoprotein-driven PTP oxidation, and
      suggest that interference with FLT3ITD-STAT5-NOX4-mediated overproduction of ROS
      and PTP inactivation may have therapeutic potential in a subset of AML. 

PMID- 26308774
TI  - Courage and character, leaders and legends: an interview with Allan D. Kirk, MD,
      PhD, FACS.

PMID- 26308775
TI  - Better Together: Transplant Quality Listserv.

PMID- 26308776
TI  - Organ Transplant Articles From China.

PMID- 26308777
TI  - Burnout in transplant nurses.
AB  - Context-Burnout is a response to chronic strain within the workplace and is
      common across nursing professions. Little has been published about burnout in
      organ transplant nurses. Objective-To report the prevalence of the 3 main
      components of burnout (emotional exhaustion, depersonalization, and reduced
      personal accomplishment) in organ transplant nurses and to examine factors that
      contribute to the development of burnout in transplant nurses. Design-Cross
      sectional survey of transplant nurses (recruited via listservs) on professional
      and personal demographics, decisional authority, psychological job demands,
      supervisor and coworker support, frequency and comfort with difficult patient
      interactions, and burnout. Participants-369 transplant nurses. Results-About half
      reported high levels of emotional exhaustion, 15.7% reported high levels of
      depersonalization, and 51.8% reported low levels of personal accomplishment.
      Working more hours per week, lower decisional authority, greater psychological
      job demands, lower perceived supervisor support, and greater frequency and
      discomfort with difficult patient interactions were significant predictors of
      emotional exhaustion. Greater frequency and discomfort with difficult patient
      interactions were significant predictors of depersonalization. Younger age, lower
      decisional authority, and greater discomfort with difficult patient interactions
      were predictors of low personal accomplishment. Conclusions-The study provides
      strong evidence of the presence of burnout in transplant nurses and opportunities
      for focused and potentially very effective interventions aimed at reducing
      burnout. 

PMID- 26308778
TI  - Self-reports on symptoms of alcohol abuse: liver transplant patients versus
      rehabilitation therapy patients.
AB  - Context-Self-report measures often underestimate the severity of symptoms of
      alcohol abuse. It is generally supposed that patients who abuse alcohol tend to
      minimize their drinking behavior. However, the validity of self-reports also can
      be influenced by external factors such as the setting. Objective-To investigate
      how the setting influences self-reporting on symptoms of alcohol abuse in
      patients with alcoholic liver disease. Design, Setting and Participants-Cross
      sectional study in patients before liver transplant (n = 40) and patients in
      rehabilitation therapy (n = 44). Main Outcome Measure-Scores on the Munich
      Alcoholism Test, which consists of a self-report-scale and an expert-rating
      scale. Results-The discrepancy in scores on the self-report scale and the expert
      rating scale differed significantly between patients before liver transplant and
      patients in rehabilitation therapy. Furthermore, patients in the rehabilitation
      therapy group reported higher alcoholism scores on the self-report questionnaire
      than did patients before liver transplant, but the groups did not differ in the
      expert evaluation value. Conclusion-The transplant setting seems to evoke
      minimizing in self-reports in patients with alcohol abuse. Minimizing or denying
      symptoms of alcohol abuse does not seem to be a specific characteristic of
      persons with alcohol abuse, as it is also caused by the circumstances. In the
      transplant setting, more attention should be given to the psychologically
      difficult situation for patients with potential alcohol abuse. Implementation of
      psychoeducational interventions in the treatment process before transplant could
      be a first step toward reaching this goal. 

PMID- 26308779
TI  - Tolerability of low-dose sulfamethoxazole/trimethoprim for Pneumocystis jirovecii
      pneumonia prophylaxis in kidney transplant recipients.
AB  - Background- Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection
      seen in immunosuppressed patients, including solid-organ transplant recipients.
      Sulfamethoxazole/trimethoprim (SMX/TMP) has long been considered first-line
      therapy for PCP prophylaxis. Optimal dosing regimens in solid-organ transplant
      recipients have not been fully defined. Objective-To examine the tolerability of
      a 1-year, 3-times weekly, prophylactic regimen of a single-strength SMX/TMP
      tablet. Study Design-Single-center, retrospective cohort study. Setting-A
      tertiary-care medical center, including inpatient hospitalizations and outpatient
      transplant clinic visits. Patients-Adult patients who received a kidney
      transplant between December 1, 2010, and November 30, 2012, at Hartford Hospital.
      Patients receiving a concurrent extrarenal transplant were excluded. Patients'
      charts were reviewed for up to 1 year after transplant. Results-A total of 88
      patients were included in the analysis. Sixty-seven patients finished a full year
      of SMX/TMP after transplant, 10 patients discontinued SMX/TMP less than 1 year
      after transplant, and 11 patients started taking atovaquone instead of SMX/TMP
      after transplant. Documented reasons for discontinuation included hyperkalemia,
      leukopenia, diarrhea, and simplification of medication regimen. Patients without
      a documented reason for discontinuation did not have any obvious anomalies in
      laboratory values that would account for the discontinuation. Patients who
      received atovaquone for PCP prophylaxis had higher rates of recurrent urinary
      tract infections than did patients who received SMX/TMP for prophylaxis (33% vs
      7%, P = .02). A longer postoperative stay (median [interquartile range, IQR] 13
      [8.25-26] days vs 7 [6-9.5] days, P = .02), higher rates of delayed graft
      function (50% vs 10%, P = .004), as well as higher serum creatinine levels on
      postoperative day 7 (6.25 [2.4-10.1] mg/dL vs 1.8 [1.2-4.2] mg/dL, P= .01),
      postoperative month 1 (1.9 [0.8] mg/dL vs 1.4 [0.5] mg/dL, P = .002), and
      postoperative month 12 (1.6 [0.5] mg/dL vs 1.3 [0.3] mg/dL, P = .04) were
      associated with early SMX/TMP discontinuation. Conclusion-A low-dose prophylactic
      SMX/TMP regimen of 1 single-strength tablet 3 times weekly is well tolerated.
      Discontinuation rates were lower than other rates reported for higher-dose
      regimens. 

PMID- 26308780
TI  - Sustainability of improvements in medication adherence through a mobile health
      intervention.
AB  - Context-Very few patient-centered, theory-guided programs for medication
      adherence and blood pressure control have been conducted in kidney transplant
      recipients. Objective-To evaluate preliminary indications of sustainability of
      improved blood pressure in kidney transplant recipients 12 months after
      completion of a 3-month randomized controlled trial of a mobile health pilot
      program to improve blood pressure and medication adherence. Participants and
      Design-A total of 18 of the 19 trial participants were contacted and all
      consented to inclusion in the retrospective analysis of their medical records
      showing their clinic-recorded systolic blood pressures at 3, 6, and 12 months
      following participation in the 3-month trial of a medical regimen self-management
      intervention. Results-A significant group difference in systolic blood pressure
      was observed longitudinally, indicating that the intervention group, as compared
      with the standard-care group, exhibited lower clinic-measured systolic blood
      pressures at the 12-month posttrial follow-up visit (P= .01). At 12-month follow
      up, success in establishing and sustaining control of systolic blood pressure
      (<131 mm Hg) was greater in the intervention group (50%) than in the control
      group (11%). Conclusion-Patients in the intervention group continued to exhibit
      lower systolic blood pressure than did patients in the control group 12 months
      after the trial ended, suggesting that the intervention may have a durable impact
      on blood pressure control that most likely reflects sustained medication
      adherence. These findings will aid in the development of an adequately powered
      randomized controlled trial to address the sustainable impact of the intervention
      program on medication adherence and blood pressure control.

PMID- 26308781
TI  - Developing a kit and video to standardize changes of left ventricular assist
      device dressings.
AB  - Context-Driveline infection is a major cause of morbidity and mortality in the
      patients with a left ventricular assist device (LVAD). Our center developed 2
      LVAD dressing change kits and instructional videos for the purpose of
      standardizing a protocol for the dressing changes. Objective-To develop 2
      different types of driveline dressing kits and videos to help in standardizing
      the education of our patients, caregivers, and staff. Design-A survey to evaluate
      patient, caregiver, and staff satisfaction and ease of use relating to the newly
      implemented dressing kits and videos. A comparison of driveline infection rates
      before and after the quality improvement project also was conducted.
      Patients/Participants, Settings-LVAD patients, their caregivers, and staff from
      Spectrum Health in Grand Rapids, Michigan. Results-Surveys were sent to 80
      patient/caregiver pairs and 330 staff members. A total of 5 patients, 10
      caregivers, and 48 staff members completed the surveys. All participants agreed
      that patients' driveline sites looked about the same, if not better than, they
      did before the kits were made available. They also overwhelmingly agreed that the
      kits were convenient (98%) and easy to use (99%). Patients and their caregivers
      gave favorable responses to the videos. The project experienced a slight increase
      in driveline infection rates, but the difference was not statistically
      significant. Conclusion-Standardizing and producing a driveline kit facilitates
      the delivery of care in an LVAD program.

PMID- 26308782
TI  - Predictors and influence of goal orientation on self-management and health
      related quality of life after lung transplant.
AB  - Context-Lung transplant recipients are encouraged to perform self-management
      behaviors to maximize health outcomes; however, performance is often less than
      ideal. Goal orientation is known to influence achievement of academic goals, but
      the influence of goal orientation on performance of self-management is unknown.
      Objectives-To identify characteristics at transplant that are predictive of
      higher goal orientation and examine relationships between Goal Orientation Index
      (GOI) subscores (Acting, Planning, Reflecting), self-management behaviors
      (adhering, self-monitoring, and communicating critical changes), and health
      related quality of life (HRQOL) at 1 year after transplant. Design-A descriptive,
      secondary analysis of data from 33 lung transplant recipients who were assessed
      at transplant and followed for 1 year as part of a clinical trial. GOI subscores
      were dichotomized at the median to categorize recipients with high and low goal
      orientation. Logistic regression was used to identify predictors of higher GOI
      subscores. Correlations between higher GOI subscores, self-management, and HRQOL
      were examined. Results-Lung transplant recipients reported relatively high mean
      GOI subscores (Acting, Planning, and Reflecting) and the 3 subscores were
      correlated (r=0.31-0.86). Self-care agency was the only significant predictor
      (P=.04) of higher GOI (Reflecting). Lung transplant recipients with higher
      Planning and Reflecting subscores were more likely to adhere (r = 0.36 and 0.46,
      respectively). Recipients with higher GOI subscores reported significantly better
      mental HRQOL (r = 0.42-0.36). Recipients with higher GOI Planning or Acting
      subscores reported significantly less anxiety (r = -0.39-0.46) and fewer
      depressive symptoms (r = -0.40-0.43). Conclusion-Assessing goal orientation may
      offer a novel approach for promoting adherence and HRQOL after lung transplant.

PMID- 26308783
TI  - Can transition to adult care for transplant recipients be improved by intensified
      services while patients are still in pediatrics?
AB  - Context-Transferring out of pediatrics is a vulnerable time for transplant
      recipients. Use of a transition coordinator before and after transfer improves
      outcomes, although it is unclear whether placing a transition coordinator in
      pediatrics alone is beneficial. Objective-To determine if incorporating a
      transition coordinator in pediatrics only is associated with stable outcomes for
      kidney transplant recipients. Design-A retrospective chart review was conducted
      on outcomes for kidney transplant recipients who shifted service location between
      2008 and 2012. Setting-A pediatric and adult transplant unit. Patients-Twenty-two
      patients transferred during the study period. Intervention-Twelve patients
      received more intensified preparation from the team's social worker, whose role
      was aligned with a transition coordinator position; 10 patients received standard
      care. Main Outcome Measures-The primary outcome was medication adherence, using a
      validated measure, standard deviations of tacrolimus blood levels. A standard
      deviation greater than 2.5 has been established as a threshold associated with
      poor outcomes such as rejection. Standard deviation of tacrolimus levels was
      compared for 1 year before and 1 year after transfer. Results-Medication
      adherence worsened from 1 year before (2.03 [SD, 0.75]) to 1 year after transfer
      (2.95 [SD, 1.38]; t = -;3.07, P = .007). A repeated-measures analysis of variance
      indicated that this pattern was the same for patients who did and patients who
      did not receive intensified services in pediatrics (F1,16 = 1.07, P = .32).

PMID- 26308784
TI  - Clinical outcomes of right-lobe split-liver versus orthotopic liver transplants
      from donors more than 70 years old.
AB  - Context-The imbalance between the organ supply and the number of potential
      transplant recipients led to consideration of expanded-criteria liver donors.
      Objective-To compare right-lobe split-liver transplants (RL-SLTs) with orthotopic
      liver transplants (OLTs) from donors more than 70 years old (OLT-O) and OLTs from
      donors less than 55 years old (OLT-Y). Methods-Seventy-one patients who received
      an RL-SLT were matched for age, sex, and Model for End-stage Liver Disease score
      with 71 patients who underwent OLT-O and 142 patients who underwent OLT-Y.
      Clinical outcomes were compared between groups. Results-Longer operation time was
      associated with RL-SLT (P< .001) as well as more blood loss (P= .03) and
      transfusions (P= .05). Postoperative morbidity was less in the OLT-Y group, with
      a lower rate of grades III to IV Clavien-Dindo complication (30%), compared with
      values in OLT-O (52%) and RL-SLT (38%). Kaplan-Meier analysis demonstrated better
      1-year and 3-year survival rates in the OLT-Y group (97% and 92%, respectively),
      compared with 92% and 86.3%, respectively, in the RL-SLT group; and 84.5% and
      73%, respectively, in the OLT-O group (P = .03). Kaplan-Meier analysis also
      demonstrated differences between the groups in terms of 1-year and 3-year graft
      survival rates, which were 92% and 86%, respectively, in OLT-Y; 77% and 66%,
      respectively, in the OLT-O, and 84.2% and 76.6%, respectively, in the RL-SLT
      group (P= .01). Conclusion-Even if OLT-Y guarantees better patient and graft
      survival, both RL-SLT and OLT-O can be used safely to expand the pool of liver
      donors, showing acceptable clinical results and complications rates. 

PMID- 26308785
TI  - What are patients saying about sex after a kidney or simultaneous kidney/pancreas
      transplant?
AB  - Context-Chronic illnesses such as kidney failure and diabetes and their
      treatments can affect people's identity, including their sexual identity. Little
      is known about patients' perspective on the effect of transplant on their sexual
      identity. Objective-To explore the sexual concerns of kidney and simultaneous
      pancreas/kidney transplant recipients. Design-Descriptive, qualitative. Setting
      Major Midwestern university hospital. Patients-143 kidney and 70 pancreas/kidney
      transplant recipients; most were male (63.0%), married (64.7%), and white
      (83.7%), and the mean age was 49 years. Intervention-The qualitative data
      reported in this manuscript are derived from 2 larger quantitative studies of
      sexuality and quality of life in kidney and pancreas/kidney transplant
      recipients. The questionnaire in those studies included 2 open-ended questions
      that allowed participants to share their experiences as transplant recipients.
      Main Outcome Measure-Two faculty and 3 students did a conventional content
      analysis on patients' responses to the open-ended questions. Codes were extracted
      from the responses and then themes were created that best represented the codes.
      Results-Participants shared how sexual concerns affected their identity as sexual
      beings after transplant. Based on the responses to these open-ended questions, 4
      themes were identified: sexual functioning, health care concerns, relationship
      with partner, and appearance changes. The study results indicate the need for
      improved education and provider-initiated dialogue related to sexuality after
      transplant.

PMID- 26308786
TI  - Racial disparity outcomes in patients undergoing hepatectomy: is baseline kidney
      function a potential explanation?
AB  - Background-Reasons underlying disparities in outcomes in liver resections between
      patients who are African American and patients who are not are poorly understood.
      Methods-An observational longitudinal cohort study was performed. Clinical data
      were collected from medical records of 166 patients (59 African American, 107
      not) undergoing partial hepatectomy between 2004 and 2012. Univariate and
      multivariate analyses were performed. Results-African Americans patients
      undergoing partial hepatectomy were more likely to be female, heavier, have
      hemangiomas or adenomas, and have hepatic steatosis on explant. Intraoperatively,
      African Americans had longer surgical times, higher estimated blood loss, and
      greater use of blood products. Major postoperative complications were
      significantly more common in African Americans. Multivariable modeling
      demonstrated that race, history of hepatitis C, and estimated blood loss were the
      only variables that were independently associated with a major complication;
      however, baseline serum creatinine level was the only variable that significantly
      modified the effect of race on complications. Conclusions-African Americans with
      normal serum creatinine levels had a similar rate of complication to patients who
      were not African American, but as the baseline serum level of creatinine
      increased, the odds ratio for a complication developing increased dramatically in
      the African American patients, suggesting that the disparities seen are
      predominantly driven by a subset of African American patients who have
      preexisting renal insufficiency. 

PMID- 26308787
TI  - Hyperuricemia and gout in solid-organ transplant: update in pharmacological
      management.
AB  - Hyperuricemia is a common comorbid condition experienced by up to 28% of kidney
      transplant recipients. These patients are at elevated risk of acute flare-ups of
      gout because of transplant-specific risk factors such as impaired renal function,
      chronic contributing pharmacotherapy (eg, calcineurin inhibitors, diuretics), and
      associated comorbid conditions. After transplant, treatment is often complicated
      by drug-drug interactions, renal impairment, and toxic effects of drugs with the
      use of first-line recommended agents. A number of therapeutic options remain
      available for transplant recipients, including dose modifications of historic
      agents and newer pharmacotherapeutic options. Notably, the Kidney Disease
      Improving Global Outcomes guidelines address the management of hyperuricemia and
      gout, but these guidelines were last published in 2009, and new data and
      treatment options have emerged since then. The management of hyperuricemia and
      acute and chronic gout is described, including the use of novel agents including
      urate oxidases, interleukin 1 inhibitors, and human urate transporter 1
      inhibitors and alternative immunosuppressive therapy strategies. 

PMID- 26308788
TI  - Update on liver transplants in Lebanon.
AB  - Objective-To review all liver transplants performed at the American University of
      Beirut Medical Center from 1998 to present. Materials and Methods-From 1998 to
      present, 21 liver transplants (15 into adults and 6 into children) were performed
      at the American University of Beirut Medical Center. Of the 21 transplants, 5
      were living related liver transplants. Results-Patient survival was 76% at 1, 5,
      and 10 years. Five recipients died at a median of 9 (range, 1-56) days after
      transplant. Causes of death included 1 case of severe cellular rejection, 1 case
      of portal and hepatic artery thrombosis, 1 case of intraoperative cardiac arrest,
      and 2 cases of primary nonfunction. Two biliary complications and 2 major
      vascular complications also occurred. All 16 survivors are well, with normal
      findings on liver function tests at a median follow-up time of 93 (range, 10-185)
      months after transplant. Conclusions-Although our numbers are small, the 10-year
      survival rate is comparable to reported rates for other series around the world.
      Deceased organ donations must be encouraged so that we can perform more
      transplants. As a source of organs, living related liver transplant is important;
      however, it cannot replace deceased donation. 

PMID- 26308789
TI  - Online Education for Transplant Professionals.

PMID- 26308790
TI  - Palladium-Catalyzed Oxidative Arylation of Tertiary Benzamides: Para-Selectivity
      of Monosubstituted Arenes.
AB  - A mild and efficient protocol for the high para-selective arylation of
      monosubstituted arenes with tertiary benzamides has been developed via palladium
      catalyzed oxidative coupling reactions. Due to the mild conditions and the easy
      availability of substrates and oxidant, this method could potentially provide a
      practical approach for the synthesis of para-substituted biaryl compounds. 

PMID- 26308791
TI  - Predictors of the application of exposure in vivo in the treatment of agoraphobia
      in an outpatient clinic: An exploratory approach.
AB  - OBJECTIVE: Although exposure in vivo is considered to be the most effective
      therapy component in the treatment of agoraphobia (AG), there is a remarkable
      lack of its application in psychotherapeutic routine care. We examined the
      severity of anxiety, psychological distress/comorbidity, therapeutic
      process/alliance, and sociodemographic status as potential predictors of in vivo
      exposure. METHOD: We applied correlational analyses and logistic regression
      analyses in a sample of N = 92 patients (main diagnosis AG) in an outpatient
      setting. RESULTS: Logistic regression analyses did not yield any significant
      single predictors, whereas a combination of a subset of predictors significantly
      predicted the application of exposure in vivo in the completer sample (R2 = .24,
      p = .041). CONCLUSION: The application of in vivo exposure may be predicted by a
      complex pattern of patient characteristics.

PMID- 26308792
TI  - Qualitative and quantitative evaluation of the BCR-ABL fusion gene in chronic
      myelogenous leukemia by flourescence in situ hybridization and molecular genetic
      methods.
AB  - AIMS: Fluorescence in situ hybridization (FISH) and quantitative real-time
      polymerase chain reaction (QRT-PCR) were used to diagnose or screen for minimal
      residual disease (MRD) in Philadelphia (Ph) chromosome-positive leukemia. We
      compared the diagnostic utility of FISH and QRT-PCR at various time points in the
      course of chronic myelogenous leukemia (CML) and to determine the mean initial
      values for patients whose QRT-PCR results were not known at the time of
      diagnosis. RESULTS: We analyzed 135 results for 78 CML patients tested by FISH
      and QRT-PCR for the Ph chromosomal translocation. All newly diagnosed cases were
      positive by both methods. On follow-up following treatment, 1 case was FISH
      positive and QRT-PCR negative; 61 cases were FISH negative and QRT-PCR positive.
      Overall concordance was 54.1%. There was good concordance between QRT-PCR results
      and cytogenetic response categories. CONCLUSIONS: We confirmed that QRT-PCR
      allows precise measurement of low levels of BCR-ABL transcripts and can serve as
      a sensitive indicator of MRD. We also demonstrated 100% correlation between QRT
      PCR and FISH in newly diagnosed CML.

PMID- 26308793
TI  - Comparison of Relative Activation Energies Obtained by Density Functional Theory
      and the Random Phase Approximation for Several Claisen Rearrangements.
AB  - We investigate several representative density functional theory approaches for
      the calculation of relative activation energies and free energies of a set of
      model pericyclic reactions, some of which have been studied experimentally. In
      particular, we use a standard hybrid functional (B3LYP), the same hybrid
      functional augmented with a basis set superposition error and dispersion
      correction, a meta-hybrid functional developed to treat transition states and
      weak interactions (M06-2X), and the recently implemented random phase
      approximation (RPA) based on Kohn-Sham orbitals from conventional density
      functional theory by Furche and co-workers. We apply these methods to calculate
      relative activation energies and estimated free energies for the amide acetal
      Claisen rearrangement. We focus on relative activation energies to assess the
      effects of steric and weak interactions in the various methods and compare with
      experiment where possible. We also discuss the advantages of using this set of
      reactions as a test bed for the comparison of treatments of weak interactions. We
      conclude that all methods yield similar trends in relative reactivity, but the
      RPA yields results in best agreement with the experimental values. 

PMID- 26308795
TI  - A model of four hierarchical levels to train Chinese residents' teaching skills
      for "practice-based learning and improvement" competency.
AB  - OBJECTIVES: The current study focused on validating a protocol for training and
      auditing the resident's practice-based learning and improvement (PBLI) and
      quality improvement (QI) competencies for primary care. METHODS: Twelve second
      year (R2), 12 first-year (R1) and 12 postgraduate year-1 residents were enrolled
      into group A, B and C, respectively, as trainees. After three training protocols
      had been completed, a writing test, self-assessed questionnaire and mini-OSTE and
      end-of-rotation assessment were used in auditing the PBLI competency, performance
      and teaching ability of trainees. RESULTS: Baseline expert-assessed PBLI and QI
      knowledge application tool writing scores were low for the R1 and R2 residents.
      After three training protocols, PBLI and QI proficiencies, performance and
      teaching abilities were improved to similar levels cross the three training
      levels of residents based on the expert-assessed writing test-audited assessments
      and on the faculty and standardized clerk-assessed end-of-rotation-/mini-OSTE
      audited assessments. CONCLUSION: The different four-level hierarchical protocols
      used to teach group A, B and C were equally beneficial and fitted their needs;
      namely the different levels of the trainees. Specifically, each level was able to
      augment their PBLI and QI proficiency. This educational intervention helps
      medical institutions to train residents as PBLI instructors.

PMID- 26308796
TI  - Exploring the population-level impact of MenB vaccination via modeling: Potential
      for serogroup replacement.
AB  - Various meningococcal conjugate vaccines exist against serogroups A, C, W and Y.
      A new protein-based vaccine targeting serogroup B (MenB) is also now available.
      The potential of such vaccines to drive serogroup replacement is considered a
      possible public health concern when implementing nationwide routine immunization
      programmes. The aim of this work was to investigate if and how serogroup
      replacement may occur following widespread vaccination with a MenB vaccine that
      may protect against carriage. To that end, we built a dynamic transmission model
      with age and serogroup stratification, focusing on European settings where most
      invasive meningococcal disease (IMD) cases are caused by serogroups B and C. For
      illustration purposes, the model was employed in 2 such settings: UK (England and
      Wales) and Czech Republic. Preliminary model-based projections suggest that,
      under strong serogroup competition for colonization, vaccine-induced serogroup
      replacement may occur even with a relatively low vaccine efficacy against
      serogroup B carriage (e.g., 20%), with potential subsequent increase in serogroup
      C IMD. The magnitude and speed of the model-projected serogroup C IMD increase
      depend on the MenB vaccination strategy, vaccine efficacy against carriage and
      the extent of any potential cross-protection against other serogroups. These
      analyses are neither exhaustive nor definitive, and focused on simulating
      potential population-level trends in IMD post-vaccination, under certain
      assumptions. Due to present inherent limitations and uncertainties, this study
      has limited quantitative value and is best regarded as an explorative qualitative
      modeling approach, to complement and challenge the current status quo, and
      suggest areas where collecting additional data may be essential. 

PMID- 26308797
TI  - Yeast microbiota of natural cavities of manatees (Trichechus inunguis and
      Trichechus manatus) in Brazil and its relevance for animal health and management
      in captivity.
AB  - The aim of this study was to characterize the yeast microbiota of natural
      cavities of manatees kept in captivity in Brazil. Sterile swabs from the oral
      cavity, nostrils, genital opening, and rectum of 50 Trichechus inunguis and 26
      Trichechus manatus were collected. The samples were plated on Sabouraud agar with
      chloramphenicol and incubated at 25  degrees C for 5 days. The yeasts isolated
      were phenotypically identified by biochemical and micromorphological tests.
      Overall, 141 strains were isolated, of which 112 were from T. inunguis (Candida
      albicans, Candida parapsilosis sensu stricto, Candida orthopsilosis, Candida
      metapsilosis, Candida guilliermondii, Candida pelliculosa, Candida tropicalis,
      Candida glabrata, Candida famata, Candida krusei, Candida norvegensis, Candida
      ciferri, Trichosporon sp., Rhodotorula sp., Cryptococcus laurentii) and 29 were
      from T. manatus (C. albicans, C. tropicalis, C. famata, C. guilliermondii, C.
      krusei, Rhodotorula sp., Rhodotorula mucilaginosa, Rhodotorula minuta,
      Trichosporon sp.). This was the first systematic study to investigate the
      importance of yeasts as components of the microbiota of sirenians, demonstrating
      the presence of potentially pathogenic species, which highlights the importance
      of maintaining adequate artificial conditions for the health of captive manatees.

PMID- 26308798
TI  - Inflammatory Cytokines Stimulate Bone Morphogenetic Protein-2 Expression and
      Release from Pancreatic Beta Cells.
AB  - The proinflammatory cytokines interleukin-1 beta (IL-1beta) and interferon gamma
      (IFN-gamma) play important roles in the progressive loss of beta-cell mass and
      function during development of both type 1 and type 2 diabetes. We have recently
      showed that bone morphogenetic protein (BMP)-2 and -4 are expressed in pancreatic
      islets and inhibit beta-cell growth and function. In this study, we describe that
      IL-1beta and IFN-gamma induce the expression of BMP-2 suggesting a possible role
      for BMP-2 in mediating the effects of IL-1beta and IFN-gamma on beta-cell
      apoptosis and dysfunction. IL-1beta increased BMP-2 mRNA levels 6- and 3-fold in
      isolated islets of Langerhans from neonatal rat and human. Downstream target
      genes of the BMP pathway were also increased by cytokine treatment and could be
      reversed by neutralization of endogenous BMP activity. Nuclear factor kappa B-
      (NFkappaB) binding sites were identified in the rat BMP-2 promoter, and reporter
      assays verified the role of NFkappaB in cytokine-induced BMP-2 expression.
      Electrophoretic mobility shift assay and chromatin immunoprecipitation assays
      confirmed NFkappaB binding to BMP-2 promoter upon IL-1beta stimulation in beta
      cells. In conclusion, we suggest that NFkappaB stimulates BMP-2 mRNA expression
      in rat and human beta cells upon cytokine exposure. 

PMID- 26308800
TI  - Synergy in Scientific Publishing: The ESA-Oxford University Press Partnership.

PMID- 26308801
TI  - Behavior of Tamarixia triozae Females (Hymenoptera: Eulophidae) Attacking
      Bactericera cockerelli (Hemiptera: Triozidae) and Effects of Three Pesticides on
      This Parasitoid.
AB  - The parasitism and host feeding behavior of Tamarixia triozae (Burks)
      (Hymenoptera: Eulophidae) females on Bactericera cockerelli (Sulc) (Hemiptera:
      Triozidae) fourth instars that have infested tomato (Lycopersicon esculentum
      Miller) leaflets are described and quantified. Females took approximately 31.14
      +/- 4.39 min to search for their first suitable host. The recognition and
      handling times for oviposition were 2.66 +/- 0.18 and 4.26 +/- 0.39 min,
      respectively. T. triozae parasitized 4.66 +/- 0.61 nymphs in a period of 6 h. The
      parasitoid explored and probed its host by walking along the margins of its body
      while antennating and repeatedly introducing the ovipositor beneath the nymph.
      The handling times before and during host feeding were 8.42 +/- 0.67 and 8.29 +/-
      0.60 min, respectively. T. triozae females consumed 1.00 +/- 0.00 B. cockerelli
      nymph after parasitizing 3.3 +/- 0.48 nymphs. EPA-a refined soybean oil
      imidacloprid, and abamectin caused between ~70 and 100% T. triozae adult
      mortality after a 48-h contact treatment with fresh pesticide residue and a 47
      91% decrease (abamectin > imidacloprid > EPA) in adult emergence when parasitized
      B. cockerelli fourth instars were directly sprayed. These data suggest that the
      use of these insecticides in combination with T. triozae in integrated pest
      management programs should be carefully evaluated.

PMID- 26308802
TI  - Can Interactions Between an Omnivorous Hemipteran and an Egg Parasitoid Limit the
      Level of Biological Control for the Tomato Pinworm?
AB  - Relationships between the omnivorous predator Nesidiocoris tenuis (Reuter) and
      the egg parasitoid Trichogramma achaeae Nagaraja and Nagarkatti were studied in
      the laboratory (no-choice and choice assays, and functional responses) and in a
      greenhouse experiment. Both natural enemies are utilized in the biological
      control of tomato pinworm on greenhouse-grown tomato crops. Three different food
      items were offered to the predator: nonparasitized prey, prey parasitized for
      less than 4 d by T. achaeae, and prey parasitized for more than 4 d by the
      parasitoid. There were significant differences in consumption of food types, with
      highest consumption for nonparasitized prey, followed by parasitized (<4 d) and
      then parasitized (>4 d), both in no-choice and choice trials. At the same time,
      the predator causes a significant mortality in the prey (over 80%) regardless of
      previous parasitism, resulting in a very coincidental intraguild predation
      detrimental to the parasitoid. It has also been observed that there was a change
      in the functional response by the predator from Type II in presence of
      nonparasitized prey to Type I when there was a combination of parasitized and
      nonparasitized prey. This represents an increase of instantaneous search rate
      (a') and a decrease of handling time (Th), which indicates a change in feeding
      behavior on the two prey types. Under greenhouse conditions, the intraguild
      predation reduced the percentage of parasitism by T. achaeae in just over 20%.
      However, when both natural enemies were present, a better control of pest Tuta
      absoluta (Meyrick) was achieved than in the case of application of any of them
      alone. 

PMID- 26308803
TI  - Introduced and Native Parasitoid Wasps Associated With Larch Casebearer
      (Lepidoptera: Coleophoridae) in Western Larch.
AB  - The larch casebearer [Coleophora laricella (Hubner)], a non-native insect,
      continues to impact western larch (Larix occidentalis Nutt.) through defoliation
      events in the Pacific Northwest. Biological control programs starting in the
      1960s released seven species of parasitoid wasps to control C. laricella
      outbreaks. However, information about current population dynamics of C. laricella
      and associated parasitoids remains lacking. Therefore, the goal of this study was
      to document the presence, current distributions, densities, and parasitism rates
      of introduced and native parasitoid wasps occurring on C. laricella throughout
      the Northwestern U.S. range of L. occidentalis. We sampled L. occidentalis trees
      at multiple sites in Oregon, Washington, Idaho, and Montana. C. laricella was
      present at all sites with average state densities ranging from 6.2 to 13.1
      moths/100 buds. We recovered two introduced hymenopteran biological control
      agents; Agathis pumila (Ratzeburg: Braconidae) at 79% of the sites, and
      Chrysocharis laricinellae (Ratzeburg: Eulophidae) at 63% of the sites. Fourteen
      species of native parasitic wasps were also recovered. The most common species
      were: Bracon sp., Spilochalcis albifrons, and Mesopolobus sp. The average native
      species parasitism rate across the four states was 9.0%, which was higher than
      the introduced species Ch. laricinellae (2.9%), but not as high as A. pumila
      (19.3%). While survey results suggest that native species may be more important
      for the control of C. laricella than previously thought, A. pumila remains the
      major source of regional control. However, further research is needed to better
      understand how introduced and native parasitoids interact to control invasive
      pest populations. 

PMID- 26308804
TI  - Challenges of Mating Disruption Using Aerosol-Emitting Pheromone Puffers in Red
      Clover Seed Production Fields to Control Coleophora deauratella (Lepidoptera:
      Coleophoridae).
AB  - Sex pheromone-mediated mating disruption using pheromone puffer dispensers was
      evaluated to control Coleophora deauratella (Lepidoptera: Coleophoridae) at three
      red clover seed production fields in Alberta, Canada. The objectives of the study
      were to determine aspects of the biology of C. deauratella which may affect
      successful mating disruption, evaluate the ability of aerosol-emitting pheromone
      puffers to reduce male moth catch in small-plot trials, and evaluate the ability
      of puffers to reduce male capture in traps, larval numbers and damage in large
      plot trials. The median longevity of male and female C. deauratella was 6 d in
      the laboratory where males emerged in larger numbers earlier than females
      (protandry). Male response to pheromone peaked at sunrise; thus, puffers were
      programmed to dispense pheromone throughout this time period. Small-plot (0.25
      ha) mating disruption trials indicated that pheromone released from puffers could
      reduce male C. deauratella orientation to traps by 60.7 +/- 18.6% compared with
      that in untreated control plots. Reduction of male orientation to traps in large
      plot (5 ha) trials over the course of the season was also successful (93.7 +/-
      1.6%). However, there was no corresponding decrease in larval numbers or increase
      in seed yield in pheromone-treated plots. Challenges of mating disruption of C.
      deauratella appear to be immigration of mated females combined with high
      population densities.

PMID- 26308805
TI  - Density-Dependent Effects of an Invasive Ant on a Ground-Dwelling Arthropod
      Community.
AB  - It is frequently assumed that an invasive species that is ecologically or
      economically damaging in one region, will typically be so in other environments.
      The Argentine ant Linepithema humile (Mayr) is listed among the world's worst
      invaders. It commonly displaces resident ant species where it occurs at high
      population densities, and may also reduce densities of other ground-dwelling
      arthropods. We investigated the effect of varying Argentine ant abundance on
      resident ant and nonant arthropod species richness and abundance in seven cities
      across its range in New Zealand. Pitfall traps were used to compare an invaded
      and uninvaded site in each city. Invaded sites were selected based on natural
      varying abundance of Argentine ant populations. Argentine ant density had a
      significant negative effect on epigaeic ant abundance and species richness, but
      hypogaeic ant abundance and species richness was unaffected. We observed a
      significant decrease in Diplopoda abundance with increasing Argentine ant
      abundance, while Coleoptera abundance increased. The effect on Amphipoda and
      Isopoda depended strongly on climate. The severity of the impact on negatively
      affected taxa was reduced in areas where Argentine ant densities were low.
      Surprisingly, Argentine ants had no effect on the abundance of the other
      arthropod taxa examined. Morphospecies richness for all nonant arthropod taxa was
      unaffected by Argentine ant abundance. Species that are established as invasive
      in one location therefore cannot be assumed to be invasive in other locations
      based on presence alone. Appropriate management decisions should reflect this
      knowledge. 

PMID- 26308799
TI  - Latest developments in our understanding of the pathogenesis of mesothelioma and
      the design of targeted therapies.
AB  - Malignant mesothelioma is an aggressive cancer whose pathogenesis is causally
      linked to occupational exposure to asbestos. Familial clusters of mesotheliomas
      have been observed in settings of genetic predisposition. Mesothelioma incidence
      is anticipated to increase worldwide in the next two decades. Novel treatments
      are needed, as current treatment modalities may improve the quality of life, but
      have shown modest effects in improving overall survival. Increasing knowledge on
      the molecular characteristics of mesothelioma has led to the development of novel
      potential therapeutic strategies, including: molecular targeted approaches, that
      is the inhibition of vascular endothelial growth factor with bevacizumab;
      immunotherapy with chimeric monoclonal antibody, immunotoxin, antibody drug
      conjugate, vaccine and viruses; inhibition of asbestos-induced inflammation, that
      is aspirin inhibition of HMGB1 activity may decrease or delay mesothelioma onset
      and/or growth. We elaborate on the rationale behind new therapeutic strategies,
      and summarize available preclinical and clinical results, as well as efforts
      still ongoing. 

PMID- 26308806
TI  - Climatic Variables Do Not Directly Predict Spider Richness and Abundance in
      Semiarid Caatinga Vegetation, Brazil.
AB  - Spiders are abundant in tropical ecosystems and exert predatory pressure on a
      wide variety of invertebrate populations and also serve as prey for many others
      organisms, being part of complex interrelationships influenced directly and
      indirectly by a myriad of factors. We examined the influence of biotic (i.e.,
      prey availability) and abiotic (i.e., temperature, precipitation, relative
      humidity, real evapotranspiration) factors on species richness and abundance
      during a two-year period in the semiarid Caatinga vegetation in northeastern
      Brazil. Data were analyzed through partial autocorrelation functions, cross
      correlations, and a path analysis. A total of 2522 spiders were collected with
      beating tray, pit-fall traps, and malaise traps, comprising 91 species and 34
      families. Spider abundance peaked in the rainy season. Our results suggest that
      total invertebrate abundance has a direct influence on spider richness and
      abundance, whereas the effects of precipitation were mainly indirectly related to
      most spider assemblage parameters. The increase in vegetation cover with the
      rainy season in the Caatinga provides more breeding and foraging sites for
      spiders and stimulates their activities. Additionally, rainfall in arid and
      semiarid ecosystems stimulated the activity and reproduction of many herbivore
      and detritivore invertebrates dependent on plant biomass and necromass
      consumption, leading to an increase in spider prey availability. 

PMID- 26308807
TI  - Intraguild Interactions of Native and Introduced Coccinellids: The Decline of a
      Flagship Species.
AB  - The decline of Coccinella novemnotata Herbst, the ninespotted lady beetle, across
      North America has been attributed to the introduction of Coccinella
      septempunctata L. It has been suggested that C. septempunctata negatively
      impacted C. novemnotata through a combination of mechanisms. We investigated the
      effects of scramble competition and intraguild predation between groups of C.
      septempunctata and C. novemnotata. A novel aspect of these experiments for this
      species combination was that we provided beetles the option to cannibalize
      conspecifics or predate on heterospecifics (i.e. intraguild predation); thus, we
      were able to compare interspecific versus intraspecific competition. Increasing
      prey density resulted in significantly lower rates of intraguild predation on C.
      novemnotata by C. septempunctata. Percentage survival of C. novemnotata grouped
      with C. septempunctata at low and high aphid densities was 6 and 61%,
      respectively. For our second study, we increased the spatial complexity and
      volume of the assay system, and provided prey ad libitum. C. novemnotata survival
      from first-instar to adult was significantly lower than C. septempunctata
      survival when grouped heterospecifically (43 vs 61% survival, respectively).
      Finally, we conducted a study to determine if hungry larvae discriminate
      conspecific versus heterospecific larvae by testing whether they predated
      selectively on the basis of species, which they did not appear to do. We conclude
      that C. novemnotata larvae suffer greater rates of intraguild predation from C.
      septempunctata compared with cannibalism, that this difference appears to be due
      to size asymmetry between the two species, and that local conditions impact the
      severity of intraguild predation by C. septempunctata. 

PMID- 26308808
TI  - Loss of Genetic Variation in Laboratory Colonies of Chilo suppressalis
      (Lepidoptera: Crambidae) Revealed by Mitochondrial and Microsatellite DNA
      Markers.
AB  - The Asiatic rice borer, Chilo suppressalis (Walker), is an important insect pest
      of rice in China. The genetic variation of a set of laboratory colonies of C.
      suppressalis was compared with their source populations in the wild (laboratory
      colonies BJCK, BJ1AB, and BJ1AC versus wild population BJW; laboratory colonies
      FZCK and FZ1CA versus wild population FZW) and was analyzed using eight
      microsatellite markers and two partial mitochondrial DNA (mtDNA) regions (COI and
      COII). Results from both analyses revealed similar patterns. Microsatellite DNA
      analysis showed that the two wild populations (BJW and FZW) harbored more private
      alleles and had higher levels of gene diversity, and observed and expected
      heterozygosity, compared with the laboratory colonies. Mitochondrial DNA analysis
      revealed that the two wild populations (BJW and FZW) had higher numbers of
      haplotypes compared with the five laboratory colonies. The three Beijing
      laboratory-reared colonies (BJ1CK, BJ1AB, and BJ1AC) had one fixed haplotype
      (H04). Most of the pairwise FST values based on mtDNA were high and all pairwise
      FST comparisons based on microsatellite DNA were significant, which indicated
      that the significant differences between these colonies and populations. Genetic
      drift caused by several factors, such as founder effect, small effective
      population size, rearing protocols, and inbreeding, can contribute to the rapid
      loss of genetic variation and affect the distribution of alleles and haplotypes.
      Therefore, it is necessary to increase the sample size of source populations to
      prevent the loss of genetic variation and genetic differentiation between
      different colonies. 

PMID- 26308809
TI  - Scymnus camptodromus (Coleoptera: Coccinellidae) Larval Development and Predation
      of Hemlock Woolly Adelgid (Hemiptera: Adelgidae).
AB  - Development time and prey consumption of Scymnus (Neopullus) camptodromus Yu and
      Liu (Coleoptera: Coccinellidae) larvae by instar, strain, and temperature were
      evaluated. S. camptodromus, a specialist predator of hemlock woolly adelgid
      Adelges tsugae (Annand) (Hemiptera: Adelgidae), was brought to the United States
      from China as a potential biological control agent for A. tsugae. This beetle has
      been approved for removal from quarantine but has not yet been field released. We
      observed that temperature had significant effects on the predator's life history.
      The larvae tended to develop faster and consume more eggs of A. tsugae per day as
      rearing temperature increased. Mean egg consumption per day of A. tsugae was less
      at 15 degrees C than at 20 degrees C. However, as larvae took longer to develop
      at the lower temperature, the total number of eggs consumed per instar during
      larval development did not differ significantly between the two temperatures. The
      lower temperature threshold for predator larval development was estimated to be 5
      degrees C, which closely matches the developmental threshold of A. tsugae
      progrediens. Accumulated degree-days for 50% of the predator neonates to reach
      adulthood was estimated to be 424. Although temperature had a significant effect
      on larval development and predation, it did not impact survival, size, or sex
      ratio of the predator at 15 and 20 degrees C. Furthermore, no remarkable
      distinctions were observed among different geographical populations of the
      predator. 

PMID- 26308810
TI  - Temperature-Dependent Functional Response of Spalangia cameroni (Hymenoptera:
      Pteromalidae), a Parasitoid of Stomoxys calcitrans (Diptera: Muscidae).
AB  - The effects of host density, temperature, and burial depths on the functional
      response of the synovigenic parasitoid Spalangia cameroni (Perkins) attacking
      pupae of the stable fly Stomoxys calcitrans (L.) were examined. Five temperatures
      (15, 20, 25, 30, and 35 degrees C), six host densities (2, 4, 8, 16, 32, and 64
      pupae per 19.64 cm(2)), and three burial depths in whole wheat grains (0, 8, and
      16 cm) were used. It was demonstrated that temperature had a profound effect on
      the functional response, whereas burial depths of the pupae played a minor role.
      For all temperatures, the functional response was of type 2 with an upper
      asymptote that depends on the temperature. Data were fitted by a functional
      response model where only the maximum attack rate is temperature dependent. The
      model shows that the optimal temperature for S. cameroni for attacking S.
      calcitrans pupae is 28.6 degrees C, where the maximum attack rate is 20.2 pupae
      day(-1). The lower and upper temperature thresholds for attacks were found as 8.1
      and 36.6 degrees C, respectively. The temperature range for attacks that resulted
      in successful parasitism was narrower, namely, 15.0 and 35.5 degrees C. Maximum
      rate of successful parasitism was estimated to be 18.2 progeny day(-1) occurring
      at 27.9 degrees C. The proportion of attacks resulting in successful parasitism
      increased steeply with temperatures >15 degrees C and declined steeply at
      temperatures >30 degrees C.

PMID- 26308811
TI  - Determination of Gibberellic Acid (GA3)-Induced Oxidative Stress in a Model
      Organism Galleria mellonella L. (Lepidoptera: Pyralidae).
AB  - The plant growth regulator gibberellic acid (GA3) is known to negatively impact
      growth and development of insects. In this study, larvae of Galleria mellonella
      L. (Lepidoptera: Pyralidae) were fed a diet with varying dosages of GA3 to
      investigate how antioxidant enzymes are influenced. Activity levels in last
      instars reared in laboratory at 25 +/- 2 degrees C, 60 +/- 5% relative humidity,
      and a photoperiod of 12:12 (L:D) h were measured for superoxide dismutase (SOD),
      glutathione S-transferase (GST), and catalase (CAT). Treatment with GA3 in diet
      resulted in a remarkable increase in the activities of both SOD and GST at lower
      GA3 doses (50-1,000 ppm) with respect to control and higher doses. The activity
      of CAT in the hemolymph of last instars significantly increased at all doses when
      compared with that in the hemolymph of untreated larvae. This trend in the
      increase of CAT was not dose-wise, except for the significant increases at 2,000
      and 5,000 ppm when compared with that of untreated and all treated groups.
      Consequently, our results showed that GA3 is effective at activating the
      antioxidant defense system of insects as a source of free radical and can be
      toxic for larvae in a dose-dependent manner. Therefore, we suggest that the
      increase in the activity of GST, SOD, and CAT in larvae may indicate a
      physiological adaptability to compensate for GA3-induced stress.

PMID- 26308812
TI  - Effects of the Activity of Coprophagous Insects on Greenhouse Gas Emissions from
      Cattle Dung Pats and Changes in Amounts of Nitrogen, Carbon, and Energy.
AB  - Effects of coprophagous insects on greenhouse gas emissions from cattle dung pats
      were investigated during the initial stage in the decomposition of dung, with
      accompanying changes in nitrogen, carbon, and energy content. We set up three
      treatments with adults of Caccobius jessoensis Harold (dung beetle) and larvae of
      the fly Neomyia cornicina (F.): 1) dung with dung beetles; 2) dung with fly
      larvae; and 3) dung without insects. In these treatments, the gas flux was
      measured from air flow exiting the glass containers connected with an in vitro
      continuous gas analysis system. Total gas fluxes from dung pats with fly larvae
      were lowest in carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O). The
      presence of dung beetles significantly increased CO2 flux from dung, but reduced
      CH4 flux compared with dung without insects. Fluxes of N2O from dung pats with
      dung beetles and without insects had distinct peaks at different times after the
      start of the experiment, while N2O from dung with fly larvae was emitted in
      extremely low levels throughout the experiment. Carbon (C) content in dung with
      beetles was significantly lower than that of untreated dung pats designated as
      fresh dung, whereas that of dung with fly larvae was higher than dung with
      beetles and without insects. Nitrogen (N) content was significantly lower in dung
      with fly larvae than the other treatments. Contents of C and N in fly pupae were
      35.87 and 8.05%, respectively. During the larval growth of the fly, energy
      accumulated in the fly body was 2,830 J/g.

PMID- 26308813
TI  - The Influence of Habitat Manipulations on Beneficial Ground-Dwelling Arthropods
      in a Southeast US Organic Cropping System.
AB  - Habitat manipulations, intentional provisioning of natural vegetation along crop
      edges, have been shown to enhance beneficial epigaeic invertebrate activity in
      many agricultural settings, but little research has been conducted on this
      practice in the southeast United States. We conducted a field-scale study to
      determine if habitat manipulations along the field edges of an organic crop
      rotation increase the activity-density of beneficial ground-dwelling
      invertebrates. Pitfall traps were used to collect micro and macro ground-dwelling
      organisms in nine organic crop fields (three each of maize, soybeans, and hay;
      2.5-4.0 ha each) surrounded by four experimental habitat manipulations (planted
      native grass and prairie flowers, planted prairie flowers only, fallow
      vegetation, or mowed vegetation) during 2009 and 2010 in eastern North Carolina.
      Beneficial macro and micro invertebrates collected in these pitfall traps
      consisted primarily of Carabidae, Araneae, Collembola, and mite species. Results
      show that habitat manipulations had little effect on the activity-density of the
      dominant epigaeic invertebrates in our study system. Our results suggest that the
      activity-density of these organisms were instead determined by a combination of
      in-field characteristics, such as crop type, weed management practices, and
      within-field resources, along with the diversity of crop type in neighboring
      fields and the availability of other resources in the area.

PMID- 26308814
TI  - The Effect of Different Host Plants on Development and Survival of Nysius
      natalensis (Hemiptera: Orsillidae).
AB  - Nysius natalensis Evans (Hemiptera: Orsillidae) is a pest of sunflower in South
      Africa. Adults invade sunflower fields from their weedy hosts. The host plant
      suitability for development and survival and the effect of between-generation
      host switching were studied on different wild host plants and sunflower.
      Parameters used to assess host plant suitability were nymphal development, head
      widths, mean mass, and survival. Nymphs and adults were provided with crushed
      seed of five host plants, as well as a combination of seeds of the five species.
      Duration of the nymphal stage, development and mortality, and mean development
      time to adult were recorded. Between-generation host switching was studied by
      providing first-instar nymphs (F2) with seed of either the same plant species or
      transferred to different ones. Mean mass and mean head widths of adults (F2) were
      determined. The food source during the first and second generation, as well as
      the interaction thereof, has a significant effect on head widths of resultant
      males and females, as well as on female mass, but first-generation food did not
      have a significant effect on male mass. Feeding the F2 on sunflower proved to be
      beneficial to the false chinch bug, as it provided the heaviest males and females
      as well as females with the biggest head widths. Lack of constant availability of
      moisture had a detrimental effect on longevity. Host plant switching to sunflower
      likely happens as a result of senescence of wild host plants prior to winter. 

PMID- 26308815
TI  - Effects of Light and Water Availability on the Performance of Hemlock Woolly
      Adelgid (Hemiptera: Adelgidae).
AB  - Eastern hemlock (Tsuga canadensis (L.) Carriere) is a dominant shade-tolerant
      tree in northeastern United States that has been declining since the arrival of
      the hemlock woolly adelgid (Adelges tsugae Annand). Determining where A. tsugae
      settles under different abiotic conditions is important in understanding the
      insect's expansion. Resource availability such as light and water can affect
      herbivore selectivity and damage. We examined how A. tsugae settlement and
      survival were affected by differences in light intensity and water availability,
      and how adelgid affected tree performance growing in these different abiotic
      treatments. In a greenhouse at the University of Rhode Island, we conducted an
      experiment in which the factors light (full-sun, shaded), water (water-stressed,
      watered), and adelgid (infested, insect-free) were fully crossed for a total of
      eight treatments (20 two-year-old hemlock saplings per treatment). We measured
      photosynthesis, transpiration, water potential, relative water content, adelgid
      density, and survival throughout the experiment. Adelgid settlement was higher on
      the old-growth foliage of shaded and water-stressed trees, but their survival was
      not altered by foliage age or either abiotic factor. The trees responded more to
      the light treatments than the water treatments. Light treatments caused a
      difference in relative water content, photosynthetic rate, transpiration, and
      water potential; however, water availability did not alter these variables.
      Adelgid did not enhance the impact of these abiotic treatments. Further studies
      are needed to get a better understanding of how these abiotic factors impact
      adelgid densities and tree health, and to determine why adelgid settlement was
      higher in the shaded treatments. 

PMID- 26308816
TI  - Effects of Thrips Density, Mode of Inoculation, and Plant Age on Tomato Spotted
      Wilt Virus Transmission in Peanut Plants.
AB  - Spotted wilt caused by tomato spotted wilt virus (TSWV; family Bunyaviridae;
      genus Tospovirus) is a serious disease of peanut (Arachis hypogaea L.) in the
      southeastern United States. Peanut genotypes with field resistance to TSWV are
      effective in suppressing spotted wilt. All commercially available genotypes with
      field resistance to TSWV were developed through conventional breeding. As a part
      of the breeding process, peanut genotypes are regularly screened under field
      situations. Despite numerous advantages associated with field screening, it is
      often limited by inconsistent vector (thrips) and TSWV pressure. A greenhouse
      transmission protocol would aid in thorough screening of selected genotypes and
      conserve time. In this study, various parameters associated with TSWV
      transmission, including tobacco thrips, Frankliniella fusca (Hinds) density, mode
      of inoculation, and plant age, were evaluated. Greater incidences of TSWV
      infection were obtained with thrips-mediated inoculation when compared with
      mechanical inoculation. TSWV inoculation with three, five, and 10 thrips resulted
      in greater incidences of TSWV infection in plants than inoculation with one
      thrips. However, incidences of TSWV infection did not vary between plants
      inoculated with three, five, and 10 viruliferous thrips. With both thrips
      mediated and mechanical inoculation methods, incidences of TSWV infection in 1-wk
      old plants were greater than in 4-wk-old plants. TSWV copy numbers, as determined
      by qPCR, also decreased with plant age. Results suggest that using at least three
      thrips per plant and 1- to 2-wk-old plants would maximize TSWV infection in
      inoculated plants. 

PMID- 26308817
TI  - Mechanical Vectors Enhance Fungal Entomopathogen Reduction of the Grasshopper
      Pest Camnula pellucida (Orthoptera: Acrididae).
AB  - Mounting scientific evidence indicates that pathogens can regulate insect
      populations. However, limited dispersal and sensitivity to abiotic conditions
      often restricts pathogen regulation of host populations. While it is well
      established that arthropod biological vectors increase pathogen incidence in host
      populations, few studies have examined whether arthropod mechanical vectors (an
      organism that transmits pathogens but is not essential to the life cycle of the
      pathogen) influence host-pathogen dynamics. The importance of mechanical
      dispersal by ant scavengers, Formica fusca (L.), in a grasshopper-fungal
      entomopathogen system was investigated. We examined the ability of ants to
      mechanically disperse and transmit the pathogen, Entomophaga grylli (Fresenius)
      pathotype 1, to its host, the pest grasshopper Camnula pellucida (Scudder), in a
      series of laboratory experiments. Fungal spores were dispersed either externally
      on the ant's body surface or internally through fecal deposition. In addition, a
      third of all grasshoppers housed with fungal-inoculated ants became infected,
      indicating that ants can act as mechanical vectors of E. grylli. The effect of
      ant mechanical vectors on E. grylli incidence was also examined in a field
      experiment. Ant access to pathogen-exposed experimental grasshopper populations
      was restricted using organic ant repellent, thereby allowing us to directly
      compare mechanical and natural transmission. Ants increased grasshopper pathogen
      mortality by 58%, which led to greater pathogen reductions of grasshopper
      survival than natural transmission. Taken together, our results indicate that
      ants enhance E. grylli reduction of grasshopper pest numbers. Therefore,
      mechanical transmission of pathogens may be an important overlooking component of
      this grasshopper-fungal pathogen system. 

PMID- 26308818
TI  - Survival and Near Extinction of Hemlock Woolly Adelgid (Hemiptera: Adelgidae)
      During Summer Aestivation in a Hemlock Plantation.
AB  - Varying densities of the spring generation of the hemlock woolly adelgid were
      manipulated on 16 previously uninfested eastern hemlocks in an open-field
      plantation in Massachusetts. In contrast to experimentally created hemlock woolly
      adelgid populations in a forest, as reported previously, there was no evidence of
      density-dependent survival on a tree-wide basis in the plantation in the spring
      (progrediens) generation. There was, however, comparable density-dependent
      survival of settled crawlers and sexupara production when samples of the
      population were examined from branches with high density. Plantation hemlocks had
      9.3 times more foliage and 10 times lower adelgid densities per cm than the
      forest hemlocks. These results show that density-dependent processes in the
      progrediens generation may only be evident when hemlock woolly adelgid density
      reaches a critical threshold. In the sistens generation that begins in midsummer,
      we counted a mean of 126 settled crawlers on marked branch on all 16 trees, but
      none of these adelgids survived the mid-summer aestivation phase, perhaps due to
      higher temperatures that were recorded in the plantation compared with a nearby
      hemlock forest, where 16% of the adelgids survived the aestivation phase. Whole
      tree counts of overwintering adelgids revealed that the adelgid populations had
      gone extinct on 13 out of the 16 trees. Mortality in the midsummer aestivation
      phase often exceeds overwintering mortality that has been widely thought to be
      the main factor that limits adelgid population growth and spread, particularly in
      northern states. 

PMID- 26308819
TI  - Influence of Mortality Factors and Host Resistance on the Population Dynamics of
      Emerald Ash Borer (Coleoptera: Buprestidae) in Urban Forests.
AB  - The success of emerald ash borer (Agrilus planipennis Fairmaire) in North America
      is hypothesized to be due to both the lack of significant natural enemies
      permitting easy establishment and a population of trees that lack the ability to
      defend themselves, which allows populations to grow unchecked. Since its
      discovery in 2002, a number of studies have examined mortality factors of the
      insect in forests, but none have examined the role of natural enemies and other
      mortality agents in the urban forest. This is significant because it is in the
      urban forest where the emerald ash borer has had the most significant economic
      impacts. We studied populations in urban forests in three municipalities in
      Ontario, Canada, between 2010 and 2012 using life tables and stage-specific
      survivorship to analyze data from a split-rearing manipulative experiment. We
      found that there was little overall mortality caused by natural enemies; most
      mortality we did observe was caused by disease. Stage-specific survivorship was
      lowest in small and large larvae, supporting previous observations of high
      mortality in these two stages. We also used our data to test the hypothesis that
      mortality and density in emerald ash borer are linked. Our results support the
      prediction of a negative relationship between mortality and density. However, the
      relationship varies between insects developing in the crown and those in the
      trunk of the tree. This relationship was significant because when incorporated
      with previous findings, it suggests a mechanism and hypothesis to explain the
      outbreak dynamics of the emerald ash borer. 

PMID- 26308820
TI  - Influence of Crop Management and Environmental Factors on Wolf Spider Assemblages
      (Araneae: Lycosidae) in an Australian Cotton Cropping System.
AB  - Wolf spiders (Lycosidae) are the most abundant ground-hunting spiders in the
      Australian cotton (Gossypium hirsutum L.) agroecosystems. These spiders have
      potential in controlling pest bollworms, Helicoverpa spp. (Lepidoptera:
      Noctuidae) in minimum-tilled fields. A study was carried out during a wet growing
      season (2011-2012) in Narrabri, New South Wales, Australia, to determine how
      different crop rotations and tillage affect wolf spider assemblages in cotton
      fields. Spider abundance and species richness did not differ significantly
      between simple plots (no winter crop) and complex plots (cotton-wheat Triticum
      aestivum L.-vetch Vicia benghalensis L. rotation). However, the wolf spider
      biodiversity, as expressed by the Shannon-Weaver and Simpson's indices, was
      significantly higher in complex plots. Higher biodiversity reflected a more even
      distribution of the most dominant species (Venatrix konei Berland, Hogna
      crispipes Koch, and Tasmanicosa leuckartii Thorell) and the presence of more rare
      species in complex plots. T. leuckartii was more abundant in complex plots and
      appears to be sensitive to farming disturbances, whereas V. konei and H.
      crispipes were similarly abundant in the two plot types, suggesting higher
      resilience or recolonizing abilities. The demographic structure of these three
      species varied through the season, but not between plot types. Environmental
      variables had a significant effect on spider assemblage, but effects of
      environment and plot treatment were overshadowed by the seasonal progression of
      cotton stages. Maintaining a high density and even distribution of wolf spiders
      that prey on Helicoverpa spp. should be considered as a conservation biological
      control element when implementing agronomic and pest management strategies. 

PMID- 26308827
TI  - Effect of Different Interrepetition Rest Periods on Barbell Velocity Loss During
      the Ballistic Bench Press Exercise.
AB  - This study investigated the effect of introducing different interrepetition rest
      (IRR) periods on the ability to sustain maximum bench press throw velocity with a
      range of loads commonly used to develop upper-body power. Thirty-four physically
      active collegiate men (age: 21.5 +/- 2.8 years; body mass: 75.2 +/- 7.2 kg;
      height: 176.9 +/- 4.9 cm) were tested during 2 consecutive weeks. During the
      first week, the maximum dynamic strength (repetition maximum [RM]) in bench press
      exercise was determined (RM = 76.7 +/- 13.2 kg). The following week, 3 testing
      sessions were conducted with 48 hours apart in random order. In each day of
      evaluation, only 1 load (30%RM, 40%RM, or 50%RM) was assessed in the bench press
      throw exercise. With each load, subjects performed 3 single sets of 15
      repetitions (15-minute interset rest) with 3 different sets configurations:
      continuous repetitions (CR), 6 seconds of IRR (IRR6), and 12 seconds of IRR
      (IRR12). The decrease of peak velocity (PV) was significantly lower for IRR12
      compared with CR and IRR6 at least since the repetition 4. No differences between
      CR and IRR6 protocols were found until the repetition 7 at 30%RM and 40%RM and
      until the repetition 5 at 50%RM. The decrease of PV during the CR protocol was
      virtually linear for the 3 loads analyzed (r > 0.99); however, this linear
      relationship became weaker for IRR6 (r = 0.79-0.95) and IRR12 (r = 0.35-0.87).
      These results demonstrate that IRR periods allow increasing the number of
      repetitions before the onset of significant velocity losses.

PMID- 26308821
TI  - Survival and Development of Spodoptera frugiperda and Chrysodeixis includens
      (Lepidoptera: Noctuidae) on Bt Cotton and Implications for Resistance Management
      Strategies in Brazil.
AB  - In Brazil, Spodoptera frugiperda (J. E. Smith) and Chrysodeixis includens
      (Walker) are important cotton pests and target of control of Bollgard II
      (Cry1Ac/Cry2Ab2) and WideStrike (Cry1Ac/Cry1F) cotton technologies. To subsidize
      an insect resistance management program, we conducted laboratory studies to
      evaluate the toxicity of these Bt cotton plants throughout larval development of
      S. frugiperda and C. includens. In bioassays with leaf disc, the efficacy of both
      Bt cotton plants against neonates was >80% for S. frugiperda and 100% for C.
      includens. However, S. frugiperda larvae that survived on Bt cotton had >76% of
      growth inhibition and stunting. In bioassays with S. frugiperda and C. includens
      larvae fed on non-Bt near-isoline during different time period (from 3 to 18 d)
      and then transferred to Bollgard II or WideStrike leaves showed that larval
      susceptibility decreased as larval age increased. For Bollgard II cotton, in all
      S. frugiperda instars, there were larvae that reached the pupal and adult stages.
      In contrast, on WideStrike cotton, a few larvae in fifth and sixth instar
      completed the biological cycle. For C. includens, some larvae in sixth instar
      originated adults in both Bt cotton plants. In conclusion, Bollgard II and
      WideStrike cotton technologies showed high efficacy against neonates of S.
      frugiperda and C. includens. However, the mortality of these species decreases as
      larval age increase, allowing insect survival in a possible seed mixture
      environment and favoring the resistance evolution.

PMID- 26308828
TI  - Decreasing Power Output Increases Aerobic Contribution During Low-Volume Severe
      Intensity Intermittent Exercise.
AB  - High-intensity interval training applied at submaximal, maximal, and supramaximal
      intensities for exercising at V[Combining Dot Above]O2max (t95V[Combining Dot
      Above]O2max) has shown similar adaptation to low-volume sprint interval training
      among active subjects. Thus, the aim of the present study was to investigate
      t95V[Combining Dot Above]O2max during 2 different intermittent exercises in the
      severe-intensity domain (e.g., range of power outputs over which V[Combining Dot
      Above]O2max can be elicited during constant-load exercise) and to identify an
      exercise protocol that reduces the time required to promote higher aerobic
      demand. Eight active men (22 +/- 2 years, 72 +/- 5 kg, 174 +/- 4 cm, 47 +/- 8
      ml.kg.min) completed the following protocols on a cycle ergometer: (a)
      incremental test, (b) determination of critical power (CP), (c) determination of
      the highest constant intensity (IHIGH) and the lowest exercise duration (TLOW) in
      which V[Combining Dot Above]O2max is attained, and (d) 2 exercise sessions in a
      randomized order that consisted of a constant power output (CPO) session at IHIGH
      and a decreasing power output (DPO) session that applied a decreasing work rate
      profile from IHIGH to 110% of CP. Time to exhaustion was significantly longer in
      DPO (371 +/- 57 seconds vs. 225 +/- 33 seconds). Moreover, t95V[Combining Dot
      Above]O2max (186 +/- 72 seconds vs. 76 +/- 49 seconds) and O2 consumed (29 +/- 4
      L vs. 17 +/- 3 L) were higher in DPO when compared with the CPO protocol. In
      conclusion, data suggest that the application of a DPO protocol during
      intermittent exercise increases the time spent at high percentages of V[Combining
      Dot Above]O2max.

PMID- 26308829
TI  - Comparison of the Capacity of Different Jump and Sprint Field Tests to Detect
      Neuromuscular Fatigue.
AB  - Different jump and sprint tests have been used to assess neuromuscular fatigue,
      but the test with optimal validity remains to be established. The current
      investigation examined the suitability of vertical jump (countermovement jump
      [CMJ], squat jump [SJ], drop jump [DJ]) and 20-m sprint (SPRINT) testing for
      neuromuscular fatigue detection. On 6 separate occasions, 11 male team-sport
      athletes performed 6 CMJ, SJ, DJ, and 3 SPRINT trials. Repeatability was
      determined on the first 3 visits, with subsequent 3 visits (0-, 24-, and 72-hour
      postexercise) following a fatiguing Yo-Yo running protocol. SPRINT performance
      was most repeatable (mean coefficient of variation <=2%), whereas DJ testing
      (4.8%) was significantly less repeatable than CMJ (3.0%) and SJ (3.5%). Each test
      displayed large decreases at 0-hour (33 of 49 total variables; mean effect size =
      1.82), with fewer and smaller decreases at 24-hour postexercise (13 variables;
      0.75), and 72-hour postexercise (19 variables; 0.78). SPRINT displayed the
      largest decreases at 0-hour (3.65) but was subsequently unchanged, whereas SJ
      performance recovered by 72-hour postexercise. In contrast, CMJ and DJ
      performance displayed moderate (12 variables; 1.18) and small (6 variables; 0.53)
      reductions at 72-hour postexercise, respectively. Consequently, the high
      repeatability and immediate and prolonged fatigue-induced changes indicated CMJ
      testing as most suitable for neuromuscular fatigue monitoring.

PMID- 26308830
TI  - Lunging Exercise Potentiates a Transient Improvement in Neuromuscular Performance
      in Young Adults.
AB  - High-load resistance-based exercise is a common approach to facilitating improved
      neuromuscular performance via postactivation potentiation. Popular field-based
      warm-up activities, however, have been largely overlooked despite their
      specificity and practicality for sports performance. Therefore, the aim of this
      study was to investigate the effect of repeated bouts of alternating lunges on
      neuromuscular performance determined by a maximal vertical jump (VJ). Forty-three
      healthy young adults (24 women and 19 men: age, 25.6 +/- 4.4 years) participated
      in the study. Maximal VJ performance was quantified by jump height (in
      centimeters), relative impulse (in N.s.kg), flight time (in seconds), and
      normalized peak vertical ground reaction force (GRFz, bodyweight [BW]) at
      baseline and after each of 6 sets of 20 alternate split lunges. A rating of
      perceived exertion (1-10 scale) was recorded from participants before each VJ.
      Jump height was greater than baseline for the first 4 trials (3.1-3.8%, p <=
      0.05), but no difference to baseline was observed on subsequent trials. Although
      there were no improvements for relative impulse over repeated trials, the sixth
      trial was significantly smaller than baseline (2.35 +/- 0.38 vs. 2.26 +/- 0.35
      N.s.kg; p <= 0.001). Similarly, no improvements were observed for flight time,
      although the first, fourth, fifth, and sixth trials were reduced compared with
      baseline performance (p <= 0.01). No differences were observed for peak vertical
      GRFz (p > 0.05). In conclusion, a regimen of lunging exercise resulted in a
      transient improvement in maximal VJ performance. However, measures of flight
      time, impulse, and GRFz did not mirror the performance gain in jump height.

PMID- 26308831
TI  - Brazilian Jiu-Jitsu Simulated Competition Part I: Metabolic, Hormonal, Cellular
      Damage, and Heart Rate Responses.
AB  - The aim of this study was to analyze physiological responses in Brazilian jiu
      jitsu athletes during simulated competition. To this end, 10 athletes (age: 28 +/
      4 years, body mass: 81.8 +/- 7.4 kg, body fat: 13.0 +/- 4.8%, systematic
      practice: 11 +/- 4 years) were analyzed in simulated competition (4 matches of 10
      minutes). Blood samples were taken to assess energy demand, hormonal responses,
      and cell damage. Additionally, the heart rate variability (HRV) response was
      analyzed. The main results show that in simulated competition, during the last
      matches, athletes had lower lactate (p < 0.001), epinephrine (p < 0.001),
      norepinephrine (p < 0.001), and insulin (p = 0.002) concentrations. Increases
      observed in creatine kinase (p < 0.001), aspartate aminotransferase (p < 0.001),
      alanine aminotransferase (p = 0.007), and creatinine (p < 0.001) seen,
      especially, in the last matches are indicative of possible cell damage. The HRV
      reflected a decrease in the RR medium (average of the normal R-R intervals) (p =
      0.001) during the competition. Thus, it is concluded that successive matches from
      competition generate a gradual decrease of adrenergic and glycolytic activities,
      which is accompanied by a gradual increase in cell damage markers and decrease in
      the RR medium of the HRV.

PMID- 26308832
TI  - Influence of Whole-Body Electrostimulation on Human Red Blood Cell Deformability.
AB  - Red blood cell-nitric oxide synthase (RBC-NOS)-dependent NO production is
      essential for the maintenance of RBC deformability, which is known to improve
      oxygen supply to the working tissue. Electrostimulation of the whole body (WB
      EMS) has been shown to improve maximal strength, springiness, and jumping power
      of trained and untrained athletes. To examine whether these 2 parameters are
      associated, this study, for the first time, aimed to investigate the effects of
      an 18-week dynamic WB-EMS program on RBC deformability in addition to maximal
      strength performance (1 repetition maximum [1RM]) in elite soccer players.
      Fifteen test persons were assigned in either WB-EMS group (EG, n = 10) or
      training group (TG, n = 5). Next to their weekly training sessions, EG performed
      3 * 10 squat jumps under the influence of WB-EMS twice per week between weeks 1
      and 14 and once per week between weeks 14 and 18. Training group only performed 3
      * 10 squat jumps. Performance was assessed by a maximal strength test on the leg
      press machine (1RM). Subjects were tested at baseline and after weeks 7, 14, and
      18 with blood sampling before (Pre), 15-30 minutes after (Post), and 24 hours
      after (24-hour Post) the training. The results showed that maximal strength was
      significantly improved in EG (p < 0.01). Maximum RBC deformability (EImax)
      increased on EMS stimulus in EG while it remained unaffected in the TG. Acute
      increase in EImax at baseline was explained by an increase in RBC-NOS activation
      while chronic increase of deformability must be caused by different, yet unknown,
      mechanisms. EImax decreased between weeks 14 and 18 suggesting that 1 WB-EMS
      session per week is not sufficient to alter deformability (EImax). In contrast,
      the deformability at low shear stress (EI 3 Pa), comparable with conditions found
      in the microcirculation, significantly increased in EG until week 14, whereas in
      TG deformability only, increased until week 7 due to increasing training volume
      after the winter break. The results indicate that WB-EMS represents a useful and
      time-saving addition to conventional training sessions to improve RBC
      deformability and possibly oxygen supply to the working tissue and thus promoting
      general force components in high performance sport.

PMID- 26308833
TI  - An ORCID based synchronization framework for a national CRIS ecosystem.
AB  - PTCRIS (Portuguese Current Research Information System) is a program aiming at
      the creation and sustained development of a national integrated information
      ecosystem, to support research management according to the best international
      standards and practices. This paper reports on the experience of designing and
      prototyping a synchronization framework for PTCRIS based on ORCID (Open
      Researcher and Contributor ID). This framework embraces the "input once, re-use
      often" principle, and will enable a substantial reduction of the research output
      management burden by allowing automatic information exchange between the various
      national systems. The design of the framework followed best practices in rigorous
      software engineering, namely well-established principles in the research field of
      consistency management, and relied on formal analysis techniques and tools for
      its validation and verification. The notion of consistency between the services
      was formally specified and discussed with the stakeholders before the technical
      aspects on how to preserve said consistency were explored. Formal specification
      languages and automated verification tools were used to analyze the
      specifications and generate usage scenarios, useful for validation with the
      stakeholder and essential to certificate compliant services. 

PMID- 26308835
TI  - An Integrated Model of Suicidal Ideation in Transcultural Populations of Chinese
      Adolescents.
AB  - This study tested the model of suicidal ideation, incorporating family and
      personal factors to predict suicidal ideation with hopelessness as a mediating
      factor in the Hong Kong sample, to a sample in Shanghai. Using MGSEM, the study
      aims to investigate the personal correlates and the family correlates of suicidal
      ideation in Hong Kong and Shanghai adolescents. We integrated the family
      ecological and diathesis-stress-hopelessness models of suicidal ideation in
      connecting the correlates. A cross-sectional design was used. The full model
      achieved metric invariance and partial path-loading invariance. Family
      functioning and social problem solving negatively predicted hopelessness or
      suicidal ideation in both the Hong Kong and Shanghai adolescents. The results
      supported an integrative approach in facilitating parent-adolescent communication
      and strengthening family functioning, and reducing the use of negative social
      problem-solving styles in adolescent suicide prevention.

PMID- 26308836
TI  - Barriers and Facilitators in Providing Community Mental Health Care to Returning
      Veterans with a History of Traumatic Brain Injury and Co-occurring Mental Health
      Symptoms.
AB  - As Veterans from recent conflicts return from deployments, increasing numbers are
      seeking care for physical (e.g., history of traumatic brain injury) and mental
      health (e.g., depression, anxiety) symptoms. Data suggest that only about half of
      recent Veterans are seeking care within the Veterans Health Administration. As
      such, providers within the community are likely to require additional training to
      meet the unique needs of these Veterans and their families. Towards this end,
      meetings were held with administrators and clinicians at Colorado Community
      Mental Health Centers (CMHCs) to identify current barriers and facilitators, as
      they relate to working with Veterans with a history of TBI and co-occurring
      mental health conditions. On-whole, CMHC employees had limited experience with
      providing care to the cohort of interest. Additional training will assist with
      increasing capacity and a web-based toolkit was developed to facilitate the
      transfer of knowledge ( www.mirecc.va.gov/visn19/tbi_toolkit ). 

PMID- 26308837
TI  - A Comparison of Self-Rated and Female Partner-Rated Scales in the Assessment of
      Paternal Prenatal Depression.
AB  - Maternal depression has been widely studied but paternal depression is often
      overlooked. Depression in men is generally more difficult to detect as the
      symptoms are not apparent. Furthermore, Japanese couples tend to suppress their
      real emotions to avoid confrontation. We aimed to investigate the reliability and
      validity of the K6, K10 and PHQ-9 in assessing the mental health status of men
      when used by their pregnant partners, as well as the prevalence of paternal
      prenatal depression in a Japanese study sample. A total of 136 couples
      participated in this study. The prevalence of paternal prenatal depression
      reported by the men themselves was higher compared to that reported by their
      female partners (K6, 10.3 %; K10, 6.6 %; PHQ-9, 3.7 % vs. K6-FP, 2.2 %; K10-FP,
      1.5 %; PHQ-9-FP, 0 %, respectively). Mental health issues in men may not be
      accurately rated by their female partners, suggesting the importance of self
      rating and direct consultation.

PMID- 26308838
TI  - Brief Report: Association Between Statin Use and Cardiovascular Mortality at the
      Population Level: An Ecologic Study.
AB  - BACKGROUND: We assessed the contribution of statin use to the decline in
      cardiovascular mortality for The Netherlands over the period 1994-2010. METHODS:
      We combined aggregated mortality data from Statistics Netherlands with dispensing
      data from a representative drug dispensing database. We estimated mortality as if
      prevalence of statin use had remained at its observed 1994 levels throughout the
      period 1994-2010 for acute myocardial infarction, other ischemic heart disease,
      and cerebrovascular disease using Poisson models adjusted for various
      confounders. RESULTS: We estimated that keeping prevalence of statin use at
      observed 1994 levels would have resulted in 6.3 (95% confidence interval [CI] =
      4.9, 7.8), 1.6 (95% CI = 0.8, 2.6), and 3.4 (95% CI = 2.2, 4.6) more acute
      myocardial infarction, ischemic heart disease, and cerebrovascular deaths per
      10,000 person-years, respectively. CONCLUSION: The findings indicate that statin
      therapy was associated with decreasing national cardiovascular mortality rates in
      the period 1994 to 2010.

PMID- 26308839
TI  - Insect-Inspired Self-Motion Estimation with Dense Flow Fields--An Adaptive
      Matched Filter Approach.
AB  - The control of self-motion is a basic, but complex task for both technical and
      biological systems. Various algorithms have been proposed that allow the
      estimation of self-motion from the optic flow on the eyes. We show that two
      apparently very different approaches to solve this task, one technically and one
      biologically inspired, can be transformed into each other under certain
      conditions. One estimator of self-motion is based on a matched filter approach;
      it has been developed to describe the function of motion sensitive cells in the
      fly brain. The other estimator, the Koenderink and van Doorn (KvD) algorithm, was
      derived analytically with a technical background. If the distances to the objects
      in the environment can be assumed to be known, the two estimators are linear and
      equivalent, but are expressed in different mathematical forms. However, for most
      situations it is unrealistic to assume that the distances are known. Therefore,
      the depth structure of the environment needs to be determined in parallel to the
      self-motion parameters and leads to a non-linear problem. It is shown that the
      standard least mean square approach that is used by the KvD algorithm leads to a
      biased estimator. We derive a modification of this algorithm in order to remove
      the bias and demonstrate its improved performance by means of numerical
      simulations. For self-motion estimation it is beneficial to have a spherical
      visual field, similar to many flying insects. We show that in this case the
      representation of the depth structure of the environment derived from the optic
      flow can be simplified. Based on this result, we develop an adaptive matched
      filter approach for systems with a nearly spherical visual field. Then only eight
      parameters about the environment have to be memorized and updated during self
      motion. 

PMID- 26308840
TI  - [The prevalence of obesity and metabolic syndrome in paediatric patients with
      epilepsy treated in monotherapy with valproic acid].
AB  - INTRODUCTION: Valproic acid (VPA) is a useful antiepileptic drug for controlling
      different types of epilepsy. It has several side effects and is associated to
      increased body weight, as well as metabolic and endocrine disorders, including
      metabolic syndrome. AIM: To determine the prevalence of obesity and metabolic
      syndrome among paediatric patients with epilepsy treated in monotherapy with VPA.
      PATIENTS AND METHODS: The study was cross-sectional, observational and
      analytical. A sample of patients treated with VPA between 2010-2014 were studied
      and the body mass index (BMI), abdominal perimeter, arterial blood pressure,
      glucose, triglycerides and high density lipoproteins (HDL) were studied in search
      of obesity and metabolic syndrome. Obesity was defined as a BMI above the 95th
      percentile, and metabolic syndrome was considered if at least three of the
      following criteria were fulfilled: abdominal perimeter above the 90th percentile,
      systolic arterial pressure above the 90th percentile, triglycerides above 110
      mg/dL and HDL below 40 mg/dL. RESULTS: A total of 47 patients with a mean age of
      10.1 +/- 4 years were studied; 51.06% were males. Eight (17%) of them developed
      obesity and, of those, two (25%) had metabolic syndrome. Three patients went on
      to become overweight (6%). Statistically significant differences were observed in
      the mean age in comparison to the BMI groups, where the obese patients were
      adolescents (ANOVA, p = 0.0001) and those who took more VPA per day were the
      obese (ANOVA, p = 0.024). CONCLUSIONS: Patients treated with VPA who become obese
      may go on to develop metabolic syndrome. They require careful monitoring and, if
      they are seen to put on weight, withdrawal of the drug should be considered.

PMID- 26308841
TI  - [Effects of motor activity on cognitive performance of patients with traumatic
      brain injury during dual tasking].
AB  - INTRODUCTION: The use of dual task paradigms has revealed behavioural
      interactions between certain motor tasks, like standing or walking, and cognitive
      tasks when performed simultaneously. Despite the potential relevance of these
      findings accounting for certain neurological symptoms (i.e., falls), or for the
      design of new therapeutic interventions, there is few information available about
      such interaction effects in traumatic brain injury (TBI). AIM: To assess the
      presence of cognitive-motor interactions during dual tasking in TBI patients.
      SUBJECTS AND METHODS: Twenty TBI patients and 19 healthy matched controls
      performed two attentional and two working memory tasks (simple reaction times,
      complex reaction times, 1-back numeric, 1-back spatial) during dual task
      conditions, that is, at the same time than one motor task (standing and walking),
      and during single task conditions (without a motor task). Reaction times were
      recorded in response to all cognitive tasks. RESULTS: Patients exhibit slower
      performance than controls in all cognitive tasks (p < 0.05). While neither
      patients nor controls showed changes in reaction times in the two simpler
      attentional tasks during dual tasking as compared to single tasking conditions,
      TBI patients do exhibit improvements in working memory tasks (F(2, 74) = 2.9; p <
      0.05) during dual tasking-walking (p < 0.02). CONCLUSIONS: The possible causes of
      positive cognitive-motor interactions during simultaneous execution of motor
      working memory tasks in TBI patients are discussed, as well as the potential
      therapeutic value of dual task paradigms in the rehabilitation of these patients.

PMID- 26308842
TI  - [Gelastic seizures as the presenting symptom of infarction of the cingulate
      gyrus].
AB  - INTRODUCTION: Gelastic seizures are infrequent epileptic seizures in which the
      main manifestation is inappropriate laughter. They have a variety of causations.
      A search of the literature did not reveal any cases of pathological laughter that
      was clearly related with strokes, although there a numerous reports of non
      epileptic pathological laughter as a prodromal symptom in stroke patients (fou
      rire prodromique). We report the case of a patient with infarcted cingulate gyrus
      who progressed with gelastic seizures at onset and during the course of the
      clinical process. CASE REPORT: An 81-year-old female who suddenly presented bouts
      of difficulties in verbal expression with disconnection from the milieu that were
      accompanied by fits of unmotivated and uncontrollable laughter that lasted less
      than five minutes. Following the attacks, her level of consciousness had dropped.
      In some of the attacks there were also involuntary movements of the upper limbs.
      Resonance imaging revealed the existence of an acute ischaemic lesion in the left
      territory of the cingulate gyrus and an electroencephalogram revealed the
      existence of epileptogenic activity in the left-hand anterior temporal and
      frontal regions. CONCLUSIONS: The clinical profile, the results of the
      complementary examinations and the response to the antiepileptic treatment allow
      us to state that in the episode reported in this patient we are dealing with
      gelastic seizures related to an acute ischaemic lesion in the left cingulate
      gyrus.

PMID- 26308843
TI  - [Review of the novelties from the 2014 ECTRIMS-ACTRIMS Joint Congress, presented
      at the 7th Post-ECTRIMS meeting (I)].
AB  - For the seventh year in a row the Post-ECTRIMS Meeting has been held in Madrid
      (Spain). Renowned specialists in multiple sclerosis and national leaders in this
      area have gathered once again to discuss the novelties presented at the 2014
      ECTRIM-ACTRIMS World Congress. That meeting gave rise to this review, which will
      be published in two parts. One of the main conclusions in this first part is the
      deeper understanding of the genetic component of multiple sclerosis that we are
      acquiring, although it is still insufficient unless we bear in mind its
      interaction with the environmental risk factors of the disease or the impact of
      comorbidity and healthy habits on the patients' susceptibility and prognosis. In
      this respect, the authors insist on the fact that, in clinical practice, the
      cognitive and psychiatric disorders remain under-diagnosed and are rarely taken
      into account in clinical research. Yet, although scarce, the evidence we have
      points to the possible benefits of disease-modifying drugs and alternatives to
      treatment with selective serotonin reuptake inhibitors. Addressing the sub
      populations in multiple sclerosis and variants of the disease enhances the
      importance of an early accurate diagnosis in order to offer patients a safer and
      more personalised prognosis and treatment. Paediatric multiple sclerosis is ideal
      for studying the risk factors of the disease but, given its low prevalence, the
      use of prospective studies raises a number of doubts and there is a preference
      for conducting collaborative studies. 

PMID- 26308844
TI  - Cerebral radiation necrosis: diagnostic challenge and clinical management.
AB  - Cerebral radiation is an indispensable cornerstone in the treatment of many
      primary and metastatic brain tumors. However, besides its desired therapeutic
      effect on tumor cells, a significant proportion of patients will experience
      neurotoxic side effects as the consequence of radiotherapy. Radiation necrosis
      can result in progressive neurological symptoms and radiographic changes. To
      differentiate radiation necrosis from progressive tumor based on imaging can pose
      a diagnostic challenge because the MRI characteristics may be similar in both
      situations. Therefore, surgical biopsy and pathological confirmation is sometimes
      necessary to guide further management. Effective treatment options for cerebral
      radiation necrosis exist and should be offered to symptomatic patients. A better
      understanding of the cellular and molecular processes underlying the development
      of radiation necrosis is necessary to prevent and minimize radiation-associated
      morbidity and to improve treatment strategies. 

PMID- 26308846
TI  - [Sturge-Weber syndrome without facial nevus: frontal leptomeningeal angiomatosis
      with favourable development].

PMID- 26308847
TI  - [Red ear syndrome: a case report with good therapeutic response].

PMID- 26308849
TI  - Weaning Failure for Disproportionate Hypoxemia Caused by Paradoxical Response to
      Positive End-Expiratory Pressure in a Patient with Patent Foramen Ovale.

PMID- 26308850
TI  - Health and Human Rights in Karen State, Eastern Myanmar.
AB  - BACKGROUND: Decades of conflict in eastern Myanmar have resulted in high
      prevalence of human rights violations and poor health outcomes. While recent
      ceasefire agreements have reduced conflict in this area, it is unknown whether
      this has resulted in concomitant reductions in human rights violations. METHODS
      AND FINDINGS: We conducted a two-stage cluster survey of 686 households in
      eastern Myanmar to assess health status, access to healthcare, food security,
      exposure to human rights violations and identification of alleged perpetrators
      over the 12 months prior to January 2012, a period of near-absence of conflict in
      this region. Household hunger (FANTA-2 scale) was moderate/high in 91 (13.2%)
      households, while the proportion of households reporting food shortages in each
      month of 2011 ranged from 19.9% in December to 47.0% in September, with food
      insecurity peaking just prior to the harvest. Diarrhea prevalence in children was
      14.2% and in everyone it was 5.8%. Forced labor was the most common human rights
      violation (185 households, 24.9%), and 210 households (30.6%) reported
      experiencing one or more human rights violations in 2011. Multiple logistic
      regression analysis identified associations between human rights violations and
      poor health outcomes. CONCLUSION: Human rights violations and their health
      consequences persist despite reduced intensity of conflict in eastern Myanmar.
      Ceasefire agreements should include language that protects human rights, and
      reconciliation efforts should address the health consequences of decades of human
      rights violations.

PMID- 26308848
TI  - Network Topologies Decoding Cervical Cancer.
AB  - According to the GLOBOCAN statistics, cervical cancer is one of the leading
      causes of death among women worldwide. It is found to be gradually increasing in
      the younger population, specifically in the developing countries. We analyzed the
      protein-protein interaction networks of the uterine cervix cells for the normal
      and disease states. It was found that the disease network was less random than
      the normal one, providing an insight into the change in complexity of the
      underlying network in disease state. The study also portrayed that, the disease
      state has faster signal processing as the diameter of the underlying network was
      very close to its corresponding random control. This may be a reason for the
      normal cells to change into malignant state. Further, the analysis revealed VEGFA
      and IL-6 proteins as the distinctly high degree nodes in the disease network,
      which are known to manifest a major contribution in promoting cervical cancer.
      Our analysis, being time proficient and cost effective, provides a direction for
      developing novel drugs, therapeutic targets and biomarkers by identifying
      specific interaction patterns, that have structural importance. 

PMID- 26308851
TI  - Programmable bio-nano-chip system: a flexible point-of-care platform for
      bioscience and clinical measurements.
AB  - The development of integrated instrumentation for universal bioassay systems
      serves as a key goal for the lab-on-a-chip community. The programmable bio-nano
      chip (p-BNC) system is a versatile multiplexed and multiclass chemical- and bio
      sensing system for bioscience and clinical measurements. The system is comprised
      of two main components, a disposable cartridge and a portable analyzer. The
      customizable single-use plastic cartridges, which now can be manufactured in high
      volumes using injection molding, are designed for analytical performance, ease of
      use, reproducibility, and low cost. These labcard devices implement high surface
      area nano-structured biomarker capture elements that enable high performance
      signaling and are index-matched to real-world biological specimens. This
      detection modality, along with the convenience of on-chip fluid storage in
      blisters and self-contained waste, represents a standard process to digitize
      biological signatures at the point-of-care. A companion portable analyzer
      prototype has been developed to integrate fluid motivation, optical detection,
      and automated data analysis, and it serves as the human interface for complete
      assay automation. In this report, we provide a systems-level perspective of the p
      BNC universal biosensing platform with an emphasis on flow control, device
      integration, and automation. To demonstrate the flexibility of the p-BNC, we
      distinguish diseased and non-case patients across three significant disease
      applications: prostate cancer, ovarian cancer, and acute myocardial infarction.
      Progress towards developing a rapid 7 minute myoglobin assay is presented using
      the fully automated p-BNC system. 

PMID- 26308852
TI  - RKIP Inhibits Local Breast Cancer Invasion by Antagonizing the Transcriptional
      Activation of MMP13.
AB  - Raf Kinase Inhibitory Protein or RKIP was initially identified as a Raf-1 binding
      protein using the yeast 2-hybrid screen. RKIP inhibits the activation
      phosphorylation of MEK by Raf-1 by competitively inhibiting the binding of MEK to
      Raf-1 and thus exerting an inhibitory effect on the Raf-MEK-Erk pathway. RKIP has
      been identified as a metastasis suppressor gene. Expression of RKIP is low in
      cancer metastases. Although primary tumor growth remains unaffected, re-
      expression of RKIP inhibits cancer metastasis. Mechanistically, RKIP constrains
      metastasis by inhibiting angiogenesis, local invasion, intravasation, and
      colonization. The molecular mechanism of how RKIP inhibits these individual steps
      remains undefined. In our present study, using an unbiased PCR based screening
      and by analyzing DNA microarray expression datasets we observe that the
      expression of multiple metalloproteases (MMPs) including MMP1, MMP3, MMP10 and
      MMP13 are negatively correlated with RKIP expression in breast cancer cell lines
      and clinical samples. Since expression of MMPs by cancer cells is important for
      cancer metastasis, we hypothesize that RKIP may mediate suppression of breast
      cancer metastasis by inhibiting multiple MMPs. We show that the expression
      signature of RKIP and MMPs is better at predicting high metastatic risk than the
      individual gene. Using a combination of loss- and gain-of-function approaches, we
      find that MMP13 is the cause of RKIP-mediated inhibition of local cancer
      invasion. Interestingly expression of MMP13 alone is not sufficient to reverse
      the inhibition of breast cancer cell metastasis to the lung due to the expression
      of RKIP. We find that RKIP negatively regulates MMP13 through the Erk2 signaling
      pathway and the repression of MMP13 by RKIP is transcription factor AP-1
      independent. Together, our findings indicate that RKIP inhibits cancer cell
      invasion, in part, via MMP13 inhibition. These data also implicate RKIP in the
      regulation of MMP transcription, suggesting a potential mechanism by which RKIP
      inhibits tumor progression and metastasis. 

PMID- 26308853
TI  - Invertebrate Metacommunity Structure and Dynamics in an Andean Glacial Stream
      Network Facing Climate Change.
AB  - Under the ongoing climate change, understanding the mechanisms structuring the
      spatial distribution of aquatic species in glacial stream networks is of critical
      importance to predict the response of aquatic biodiversity in the face of glacier
      melting. In this study, we propose to use metacommunity theory as a conceptual
      framework to better understand how river network structure influences the spatial
      organization of aquatic communities in glacierized catchments. At 51 stream sites
      in an Andean glacierized catchment (Ecuador), we sampled benthic
      macroinvertebrates, measured physico-chemical and food resource conditions, and
      calculated geographical, altitudinal and glaciality distances among all sites.
      Using partial redundancy analysis, we partitioned community variation to evaluate
      the relative strength of environmental conditions (e.g., glaciality, food
      resource) vs. spatial processes (e.g., overland, watercourse, and downstream
      directional dispersal) in organizing the aquatic metacommunity. Results revealed
      that both environmental and spatial variables significantly explained community
      variation among sites. Among all environmental variables, the glacial influence
      component best explained community variation. Overland spatial variables based on
      geographical and altitudinal distances significantly affected community
      variation. Watercourse spatial variables based on glaciality distances had a
      unique significant effect on community variation. Within alpine catchment,
      glacial meltwater affects macroinvertebrate metacommunity structure in many ways.
      Indeed, the harsh environmental conditions characterizing glacial influence not
      only constitute the primary environmental filter but also, limit water-borne
      macroinvertebrate dispersal. Therefore, glacier runoff acts as an aquatic
      dispersal barrier, isolating species in headwater streams, and preventing non
      adapted species to colonize throughout the entire stream network. Under a
      scenario of glacier runoff decrease, we expect a reduction in both environmental
      filtering and dispersal limitation, inducing a taxonomic homogenization of the
      aquatic fauna in glacierized catchments as well as the extinction of specialized
      species in headwater groundwater and glacier-fed streams, and consequently an
      irreversible reduction in regional diversity. 

PMID- 26308854
TI  - Semi-Metric Topology of the Human Connectome: Sensitivity and Specificity to
      Autism and Major Depressive Disorder.
AB  - INTRODUCTION: The human functional connectome is a graphical representation,
      consisting of nodes connected by edges, of the inter-relationships of blood
      oxygenation-level dependent (BOLD) time-series measured by MRI from regions
      encompassing the cerebral cortices and, often, the cerebellum. Semi-metric
      analysis of the weighted, undirected connectome distinguishes an edge as either
      direct (metric), such that there is no alternative path that is accumulatively
      stronger, or indirect (semi-metric), where one or more alternative paths exist
      that have greater strength than the direct edge. The sensitivity and specificity
      of this method of analysis is illustrated by two case-control analyses with
      independent, matched groups of adolescents with autism spectrum conditions (ASC)
      and major depressive disorder (MDD). RESULTS: Significance differences in the
      global percentage of semi-metric edges was observed in both groups, with
      increases in ASC and decreases in MDD relative to controls. Furthermore, MDD was
      associated with regional differences in left frontal and temporal lobes, the
      right limbic system and cerebellum. In contrast, ASC had a broadly increased
      percentage of semi-metric edges with a more generalised distribution of effects
      and some areas of reduction. In summary, MDD was characterised by localised,
      large reductions in the percentage of semi-metric edges, whilst ASC is
      characterised by more generalised, subtle increases. These differences were
      corroborated in greater detail by inspection of the semi-metric backbone for each
      group; that is, the sub-graph of semi-metric edges present in >90% of
      participants, and by nodal degree differences in the semi-metric connectome.
      CONCLUSION: These encouraging results, in what we believe is the first
      application of semi-metric analysis to neuroimaging data, raise confidence in the
      methodology as potentially capable of detection and characterisation of a range
      of neurodevelopmental and psychiatric disorders.

PMID- 26308855
TI  - Extracellular Electron Transfer Is a Bottleneck in the Microbiologically
      Influenced Corrosion of C1018 Carbon Steel by the Biofilm of Sulfate-Reducing
      Bacterium Desulfovibrio vulgaris.
AB  - Carbon steels are widely used in the oil and gas industry from downhole tubing to
      transport trunk lines. Microbes form biofilms, some of which cause the so-called
      microbiologically influenced corrosion (MIC) of carbon steels. MIC by sulfate
      reducing bacteria (SRB) is often a leading cause in MIC failures. Electrogenic
      SRB sessile cells harvest extracellular electrons from elemental iron oxidation
      for energy production in their metabolism. A previous study suggested that
      electron mediators riboflavin and flavin adenine dinucleotide (FAD) both
      accelerated the MIC of 304 stainless steel by the Desulfovibrio vulgaris biofilm
      that is a corrosive SRB biofilm. Compared with stainless steels, carbon steels
      are usually far more prone to SRB attacks because SRB biofilms form much denser
      biofilms on carbon steel surfaces with a sessile cell density that is two orders
      of magnitude higher. In this work, C1018 carbon steel coupons were used in tests
      of MIC by D. vulgaris with and without an electron mediator. Experimental weight
      loss and pit depth data conclusively confirmed that both riboflavin and FAD were
      able to accelerate D. vulgaris attack against the carbon steel considerably. It
      has important implications in MIC failure analysis and MIC mitigation in the oil
      and gas industry. 

PMID- 26308857
TI  - Birth Outcomes of Latin Americans in Two Countries with Contrasting Immigration
      Admission Policies: Canada and Spain.
AB  - BACKGROUND: We delved into the selective migration hypothesis on health by
      comparing birth outcomes of Latin American immigrants giving birth in two
      receiving countries with dissimilar immigration admission policies: Canada and
      Spain. We hypothesized that a stronger immigrant selection in Canada will reflect
      more favourable outcomes among Latin Americans giving birth in Canada than among
      their counterparts giving birth in Spain. MATERIALS AND METHODS: We conducted a
      cross-sectional bi-national comparative study. We analyzed birth data of
      singleton infants born in Canada (2000-2005) (N = 31,767) and Spain (1998-2007)
      (N = 150,405) to mothers born in Spanish-speaking Latin American countries. We
      compared mean birthweight at 37-41 weeks gestation, and low birthweight and
      preterm birth rates between Latin American immigrants to Canada vs. Spain.
      Regression analysis for aggregate data was used to obtain Odds Ratios and Mean
      birthweight differences adjusted for infant sex, maternal age, parity, marital
      status, and father born in same source country. RESULTS: Latin American women in
      Canada had heavier newborns than their same-country counterparts giving birth in
      Spain, overall [adjusted mean birthweight difference: 101 grams; 95% confidence
      interval (CI): 98, 104], and within each maternal country of origin. Latin
      American women in Canada had fewer low birthweight and preterm infants than those
      giving birth in Spain [adjusted Odds Ratio: 0.88; 95% CI: 0.82, 0.94 for low
      birthweight, and 0.88; 95% CI: 0.84, 0.93 for preterm birth, respectively].
      CONCLUSION: Latin American immigrant women had better birth outcomes in Canada
      than in Spain, suggesting a more selective migration in Canada than in Spain.

PMID- 26308858
TI  - On the Morphology of a Growing City: A Heuristic Experiment Merging Static
      Economics with Dynamic Geography.
AB  - In this paper, we aim at exploring how individual location decisions affect the
      shape of a growing city and, more precisely, how they may add up to a
      configuration that diverges from equilibrium configurations formulated ex-ante.
      To do so, we provide a two-sector city model merging a static equilibrium
      analysis with agent-based simulations. Results show that under strong
      agglomeration effects, urban development is monotonic and ends up with circular,
      monocentric long-term configurations. For low agglomeration effects however,
      elongated and multicentric urban configurations may emerge. The occurrence and
      underlying dynamics of these configurations are also discussed regarding
      commuting costs and the distance-decay of agglomeration economies between firms.
      To sum up, our paper warns urban planning policy makers against the difference
      that may stand between appropriate long-term perspectives, represented here by
      analytic equilibrium configurations, and short-term urban configurations,
      simulated here by a multi-agent system. 

PMID- 26308859
TI  - Wildlife Abundance and Diversity as Indicators of Tourism Potential in Northern
      Botswana.
AB  - Wildlife tourism can provide economic incentives for conservation. Due to the
      abundance of wildlife and the presence of charismatic species some areas are
      better suited to wildlife tourism. Our first objective was to develop criteria
      based on wildlife abundance and diversity to evaluate tourism potential in the
      Northern Conservation Zone of Botswana. Secondly we wanted to quantify and
      compare tourism experiences in areas with high and low tourism potential. We used
      aerial survey data to estimate wildlife biomass and diversity to determine
      tourism potential, while data from ground surveys quantified the tourist
      experience. Areas used for High Paying Low Volume tourism had significantly
      higher mean wildlife biomass and wildlife diversity than the areas avoided for
      this type of tourism. Only 22% of the Northern Conservation Zone has intermediate
      to high tourism potential. The areas with high tourism potential, as determined
      from the aerial survey data, provided tourists with significantly better wildlife
      sightings (ground surveys) than the low tourism potential areas. Even Low Paying
      tourism may not be economically viable in concessions that lack areas with
      intermediate to high tourism potential. The largest part of the Northern
      Conservation Zone has low tourism potential, but low tourism potential is not
      equal to low conservation value. Alternative conservation strategies should be
      developed to complement the economic incentive provided by wildlife-based tourism
      in Botswana. 

PMID- 26308860
TI  - Fast Pyrolysis Behavior of Banagrass as a Function of Temperature and Volatiles
      Residence Time in a Fluidized Bed Reactor.
AB  - A reactor was designed and commissioned to study the fast pyrolysis behavior of
      banagrass as a function of temperature and volatiles residence time. Four
      temperatures between 400 and 600 degrees C were examined as well as four
      residence times between ~1.0 and 10 seconds. Pyrolysis product distributions of
      bio-oil, char and permanent gases were determined at each reaction condition. The
      elemental composition of the bio-oils and chars was also assessed. The greatest
      bio-oil yield was recorded when working at 450 degrees C with a volatiles
      residence time of 1.4 s, ~37 wt% relative to the dry ash free feedstock
      (excluding pyrolysis water). The amounts of char (organic fraction) and permanent
      gases under these conditions are ~4 wt% and 8 wt% respectively. The bio-oil yield
      stated above is for 'dry' bio-oil after rotary evaporation to remove solvent,
      which results in volatiles and pyrolysis water being removed from the bio-oil.
      The material removed during drying accounts for the remainder of the pyrolysis
      products. The 'dry' bio-oil produced under these conditions contains ~56 wt%
      carbon which is ~40 wt% of the carbon present in the feedstock. The oxygen
      content of the 450 degrees C, 1.4 s 'dry' bio-oil is ~38 wt%, which accounts for
      ~33 wt% of the oxygen in the feedstock. At higher temperature or longer residence
      time less bio-oil and char is recovered and more gas and light volatiles are
      produced. Increasing the temperature has a more significant effect on product
      yields and composition than increasing the volatiles residence time. At 600
      degrees C and a volatiles residence time of 1.2 seconds the bio-oil yield is ~21
      wt% of the daf feedstock, with a carbon content of 64 wt% of the bio-oil. The bio
      oil yield from banagrass is significantly lower than from woody biomass or
      grasses such as switchgrass or miscanthus, but is similar to barley straw. The
      reason for the low bio-oil yield from banagrass is thought to be related to its
      high ash content (8.5 wt% dry basis) and high concentration of alkali and alkali
      earth metals (totaling ~2.8 wt% relative to the dry feedstock) which are
      catalytic and increase cracking reactions during pyrolysis. 

PMID- 26308861
TI  - Observation of the retarded transportation of a photogenerated hole on epitaxial
      graphene.
AB  - Graphene is usually adopted as an assistant additive for catalysts in
      photocatalytic processes, because of its ability to accelerate the separation of
      photogenerated charge carriers. To elucidate the mechanism, hydrogen peroxide is
      adopted to convert the O2(-) active species into OH for degradation of an organic
      dye. If the pH value is less than 7, the concentration of the OH species can be
      reduced more quickly with the addition of graphene than without, because
      negatively charged electrons can be transported quickly on graphene. If the pH
      value is larger than 7, the concentration of OH can be promoted by the catalyst
      SiC with photogenerated h(+) release and reaction with OH(-), however the
      concentration is reduced if the SiC catalyst is covered by a graphene sheet, as
      it retards h(+) release from the SiC substrate. Our findings have provided a
      certification for the role of graphene in photo-catalytic processes. 

PMID- 26308862
TI  - Palladium-catalyzed direct and regioselective C-H acyloxylation of indolizines.
AB  - A direct and regioselective C1-acyloxylation of indolizines was developed via
      palladium-catalyzed C-H functionalization. A series of indolizines were
      successfully acyloxylated at the C1 position with the tolerance of a broad range
      of functional groups. In this reaction, high regioselectivity was achieved in the
      absence of a directing group. This work represents the first example of
      indolizine acyloxylation via C-H activation. 

PMID- 26308863
TI  - Inaccessible Biodiversity on Limestone Cliffs: Aster tianmenshanensis
      (Asteraceae), a New Critically Endangered Species from China.
AB  - Aster tianmenshanensis G. J. Zhang & T. G. Gao, a new species of Asteraceae from
      southern China is described and illustrated based on evidence from morphology,
      micromorphology and molecular phylogeny. The new species is superficially similar
      to Aster salwinensis Onno in having rosettes of spatulate leaves and a solitary,
      terminal capitulum, but it differs by its glabrous leaf margins, unequal disc
      floret lobes and 1-seriate pappus. The molecular phylogenetic analysis, based on
      nuclear sequences ITS, ETS and chloroplast sequence trnL-F, showed that the new
      species was nested within the genus Aster and formed a well supported clade with
      Aster verticillatus (Reinw.) Brouillet et al. The new species differs from the
      latter in having unbranched stems, much larger capitula, unequal disc floret
      lobes, beakless achenes and persistent pappus. In particular, A. tianmenshanensis
      has very short stigmatic lines, only ca. 0.18 mm long and less than 1/3 of the
      length of sterile style tip appendages, remarkably different from its congeners.
      This type of stigmatic line, as far as we know, has not been found in any other
      species of Aster. The very short stigmatic lines plus the unequal disc floret
      lobes imply that the new species may have a very specialized pollination system,
      which may be a consequence of habitat specialization. The new species grows only
      on the limestone cliffs of Mt. Tianmen, Hunan Province, at the elevation of 1400
      m. It could only be accessed when a plank walkway was built across the cliffs for
      tourists. As it is known only from an area estimated at less than 10 km2 and a
      walkway passes through this location, its habitat could be easily disturbed. This
      species should best be treated as Critically Endangered based on the
      International Union for Conservation of Nature Red List Categories and Criteria
      B2a. 

PMID- 26308865
TI  - Periodontal diagnosis in private dental practice: a case-based survey.
AB  - BACKGROUND: Despite the prevalence of periodontitis in Australia, there are few
      reports regarding periodontal diagnosis and therapies in the general dental
      practice setting. This study aimed to assess the degree of diagnostic accuracy in
      periodontal cases of Victorian general dental practitioners. METHODS: Following
      ethics approval, dentists were invited to complete a scenario-based questionnaire
      on the Australian Dental Association Victorian Branch (ADAVB) website. Five text
      based clinical scenarios (from a total of 10) were randomly presented,
      representing patients with a range of disease levels from periodontal
      health/gingivitis to severe periodontitis, and respondents were asked what
      examinations they would usually perform. Based upon the presented results of
      periodontal and radiographic examinations, a periodontal diagnosis was requested.
      RESULTS: One hundred and thirty-five dentists attempted the survey. Most were in
      group practice and based in Melbourne; 22.5% of respondents worked in a practice
      employing a hygienist. The clinical parameters most commonly measured to diagnose
      periodontal disease were pocket depth and mobility. The majority of respondents
      diagnosed health, gingivitis and mild periodontitis correctly compared to
      American Academy of Periodontology guidelines. However, moderate periodontitis
      tended to be diagnosed as severe. CONCLUSIONS: Dentists in Victoria used
      appropriate clinical parameters when assessing periodontal disease and were
      generally accurate in their diagnoses. There is a need for consensus regarding
      diagnostic definitions.

PMID- 26308864
TI  - Intracochlear Bleeding Enhances Cochlear Fibrosis and Ossification: An Animal
      Study.
AB  - The aim of this study was to investigate the effects of intracochlear bleeding
      during cochleostomy on cochlear inflammatory response and residual hearing in a
      guinea pig animal model. Auditory brainstem response threshold shifts were
      greater in blood injected ears (p<0.05). Interleukin-1beta, interleukin-10, tumor
      necrosis factor-alpha and nitric oxide synthase 2, cytokines that are related to
      early stage inflammation, were significantly increased in blood injected ears
      compared to normal and cochleostomy only ears at 1 day after surgery; with the
      increased IL-1beta being sustained until 3 days after the surgery (p<0.05). Hair
      cells were more severely damaged in blood injected ears than in cochleostomy only
      ears. Histopathologic examination revealed more extensive fibrosis and
      ossification in blood injected ears than cochleostomy only ears. These results
      show that intracochlear bleeding enhanced cochlear inflammation resulting in
      increased fibrosis and ossification in an experimental animal model. 

PMID- 26308866
TI  - Metal ion concentrations and semen quality in patients undergoing hip
      arthroplasty: A prospective comparison between metal-on-metal and metal-on
      polyethylene implants.
AB  - PURPOSE: The widespread usage of metal-on-metal (MoM) articulations in total hip
      arthroplasty (THA) has been tempered by concerns of increased metal ion
      production. The purpose of the study is to evaluate the influence of metal ion
      exposure on semen quality in young male patients undergoing THA. METHODS: Male
      patients who were scheduled for unilateral THA and aged between 20 and 45 years
      were prospectively enrolled. Patients were sorted into MoM and metal-on
      polyethylene (MoP) groups with equal case number. Semen and blood metal ion
      levels were measured and sperm analysis was performed before, 6 months after, and
      1 year after surgery. RESULTS: Compared to preoperative baseline, patients (n =
      50) in both groups had increased cobalt (Co) and chromium (Cr) concentrations in
      blood and seminal fluid after surgery. Between-group comparisons at 6 months and
      1 year after surgery showed that patients in the MoM group both had a greater Co
      concentration in blood and semen and a greater Cr concentration in blood and
      semen. Patients receiving MoM prosthesis had a reduced percentage of
      morphologically normal sperm, and decreases from the preoperative level (44.7%)
      were significant at 6 months (36.8%, p = 0.03) and 1 year (33.8%, p = 0.004).
      CONCLUSIONS: Our data shows a significantly greater concentration of metal ion in
      blood and semen in patients with MoM prosthesis with a reduced percentage of
      morphologically normal sperm. Despite small effects on sperm quality, some
      concerns remain. Further studies are necessary to determine sources of metal ion
      and to investigate effects on male fertility.

PMID- 26308868
TI  - The thinking Neanderthals: What do we know about Neanderthal cognition?
AB  - The study of Neanderthal cognition is difficult, because of the archaeological
      invisibility of cognition, and because of the methodological issues that arise
      both from that invisibility and from their being close to modern humans.
      Nevertheless, fair progress has been made in gathering relevant evidence. There
      is now good evidence that Neanderthals were cognitively sophisticated, displaying
      many of the cognitive traits that were traditionally regarded as proxies for
      modern human cognition, notably including language. It can neither be proven nor
      excluded that they were our cognitive equals, but they were close enough to us,
      biologically and cognitively, to interbreed successfully and leave a genetic
      legacy in our DNA. WIREs Cogn Sci 2014, 5:613-620. doi: 10.1002/wcs.1317 CONFLICT
      OF INTEREST: The author has declared no conflicts of interest for this article.
      For further resources related to this article, please visit the WIREs website. 

PMID- 26308867
TI  - New 3-(heteroaryl)-2-iminocoumarin-based borate complexes: synthesis,
      photophysical properties, and rational functionalization for
      biosensing/biolabeling applications.
AB  - Members of a series of boron difluoride complexes with 3-(heteroaryl)-2
      iminocoumarin ligands bearing both a phenolic hydroxyl group (acting as a
      fluorogenic center) and an N-aryl substituent (acting as a stabilizing moiety)
      have been synthesized in good yields by applying a straightforward two-step
      method. These novel fluorogenic dyes belong to the family of "Boricos" (D. Frath
      et al., Chem. Commun.- 2013, 49, 4908-4910) and are the first examples of phenol
      based fluorophores of which the photophysical properties in the green-yellow
      spectral range are dramatically improved by N,N-chelation of a boron atom.
      Modulation of their fluorescence properties through reversible chemical
      modification of their phenol moieties has been demonstrated by the preparation of
      the corresponding 2,4-dinitrophenyl (DNP) ethers, which led to a dramatic "OFF
      ON" fluorescence response upon reaction with thiols. Additionally, to expand the
      scope of these "7-hydroxy-Borico" derivatives, particularly in biolabeling, amine
      or carboxylic acid functionalities amenable to (bio)conjugation have been
      introduced within their scaffold. Their utility has been demonstrated in the
      preparation of fluorescent bovine serum albumin (BSA) conjugates and "Borico"
      DOTA-like scaffolds in an effort to design novel monomolecular multimodal
      fluorescence- radioisotope imaging agents. 

PMID- 26308869
TI  - Facial attractiveness.
AB  - Facial attractiveness has important social consequences. Despite a widespread
      belief that beauty cannot be defined, in fact, there is considerable agreement
      across individuals and cultures on what is found attractive. By considering that
      attraction and mate choice are critical components of evolutionary selection, we
      can better understand the importance of beauty. There are many traits that are
      linked to facial attractiveness in humans and each may in some way impart
      benefits to individuals who act on their preferences. If a trait is reliably
      associated with some benefit to the perceiver, then we would expect individuals
      in a population to find that trait attractive. Such an approach has highlighted
      face traits such as age, health, symmetry, and averageness, which are proposed to
      be associated with benefits and so associated with facial attractiveness. This
      view may postulate that some traits will be universally attractive; however, this
      does not preclude variation. Indeed, it would be surprising if there existed a
      template of a perfect face that was not affected by experience, environment,
      context, or the specific needs of an individual. Research on facial
      attractiveness has documented how various face traits are associated with
      attractiveness and various factors that impact on an individual's judgments of
      facial attractiveness. Overall, facial attractiveness is complex, both in the
      number of traits that determine attraction and in the large number of factors
      that can alter attraction to particular faces. A fuller understanding of facial
      beauty will come with an understanding of how these various factors interact with
      each other. WIREs Cogn Sci 2014, 5:621-634. doi: 10.1002/wcs.1316 CONFLICT OF
      INTEREST: The author has declared no conflicts of interest for this article. For
      further resources related to this article, please visit the WIREs website. 

PMID- 26308870
TI  - Attributions of consciousness.
AB  - Many philosophers and brain scientists hold that explaining consciousness is one
      of the major outstanding problems facing modern science today. One type of
      consciousness in particular-phenomenal consciousness-is thought to be especially
      problematic. The reasons given for believing that this phenomenon exists in the
      first place, however, often hinge on the claim that its existence is simply
      obvious in ordinary perceptual experience. Such claims motivate the study of
      people's intuitions about consciousness. In recent years a number of researchers
      in experimental philosophy of mind have begun to shed light on this area,
      investigating how people understand and attribute those mental states that have
      been thought to be phenomenally conscious. In this article, we discuss the
      philosophical concept of phenomenal consciousness and detail the work that has
      been done on the question of whether lay people have this concept. WIREs Cogn Sci
      2014, 5:635-648. doi: 10.1002/wcs.1320 For further resources related to this
      article, please visit the WIREs website. CONFLICT OF INTEREST: The author has
      declared no conflicts of interest for this article.

PMID- 26308871
TI  - The impact of electrical stimulation techniques on behavior.
AB  - Low-intensity transcranial electrical stimulation (tES) methods are a group of
      noninvasive brain stimulation techniques, whereby currents are applied with
      intensities typically ranging between 1 and 2 mA, through the human scalp. These
      techniques have been shown to induce changes in cortical excitability and
      activity during and after the stimulation in a reversible manner. They include
      transcranial direct current simulation (tDCS), transcranial alternating current
      simulation (tACS), and transcranial random noise stimulation (tRNS). Currently,
      an increasing number of studies have been published regarding the effects of tES
      on cognitive performance and behavior. Processes of learning and increases in
      cognitive performance are accompanied by changes in cortical plasticity. tES can
      impact upon these processes and is able to affect task execution. Many studies
      have been based on the accepted idea that by increasing cortical excitability
      (e.g., by applying anodal tDCS) or coherence of oscillatory activity (e.g., by
      applying tACS) an increase in performance should be detected; however, a number
      of studies now suggest that the basic knowledge of the mechanisms of action is
      insufficient to predict the outcome of applied stimulation on the execution of a
      cognitive or behavioral task, and so far no standard paradigms for increasing
      cortical plasticity changes during learning or cognitive tasks have been
      established. The aim of this review is to summarize recent findings with regard
      to the effects of tES on behavior concentrating on the motor and visual areas.
      WIREs Cogn Sci 2014, 5:649-659. doi: 10.1002/wcs.1319 For further resources
      related to this article, please visit the WIREs website. CONFLICT OF INTEREST:
      The authors have declared no conflicts of interest for this article.

PMID- 26308872
TI  - Animal communication.
AB  - Animal communication is first and foremost about signal transmission and aims to
      understand how communication occurs. It is a field that has contributed to and
      been inspired by other fields, from information technology to neuroscience, in
      finding ever better methods to eavesdrop on the actual 'message' that forms the
      basis of communication. Much of this review deals with vocal communication as an
      example of the questions that research on communication has tried to answer and
      it provides an historical overview of the theoretical arguments proposed. Topics
      covered include signal transmission in different environments and different
      species, referential signaling, and intentionality. The contention is that animal
      communication may reveal significant thought processes that enable some
      individuals in a small number of species so far investigated to anticipate what
      conspecifics might do, although some researchers think of such behavior as
      adaptive or worth dismissing as anthropomorphizing. The review further points out
      that some species are more likely than others to develop more complex
      communication patterns. It is a matter of asking how animals categorize their
      world and which concepts require cognitive processes and which are adaptive. The
      review concludes with questions of life history, social learning, and decision
      making, all criteria that have remained relatively unexplored in communication
      research. Long-lived, cooperative social animals have so far offered especially
      exciting prospects for investigation. There are ample opportunities and now very
      advanced technologies as well to tap further into expressions of memory of
      signals, be they vocal or expressed in other modalities. WIREs Cogn Sci 2014,
      5:661-677. doi: 10.1002/wcs.1321 For further resources related to this article,
      please visit the WIREs website. CONFLICT OF INTEREST: The author has declared no
      conflicts of interest for this article.

PMID- 26308873
TI  - Pupillometry.
AB  - Pupillometry is the study of changes in the diameter of the pupil as a function
      of cognitive processing. This review paper provides a brief historical overview
      of the study of pupillometry in cognitive science. The physiology of pupillary
      responses is introduced, leading to an outline of early pupillometry work, which
      began with the seminal work of Hess and Polt in the 1960s. The paper then
      presents a broad review of contemporary research in cognitive sciences that
      relies on pupillometry. This review is organized around five general domains,
      namely perception, language processing, memory and decision making, emotion and
      cognition, and cognitive development. In order to illustrate the nature of the
      method, and the challenges of analysis, the next section of the review details
      the process of compiling, processing, and analyzing data from a simple, typical
      pupillometry study. WIREs Cogn Sci 2014, 5:679-692. doi: 10.1002/wcs.1323 For
      further resources related to this article, please visit the WIREs website.
      CONFLICT OF INTEREST: The authors have declared no conflicts of interest for this
      article.

PMID- 26308874
TI  - Is there a link between the crafting of tools and the evolution of cognition?
AB  - The ability to craft tools is one of the defining features of our species. The
      technical intelligence hypothesis predicts that tool-making species should have
      enhanced physical cognition. Here we review how the physical problem-solving
      performance of tool-making apes and corvids compares to closely related species.
      We conclude that, while some performance differences have been found, overall the
      evidence is at best equivocal. We argue that increased sample sizes, novel
      experimental designs, and a signature-testing approach are required to determine
      the effect tool crafting has on the evolution of intelligence. WIREs Cogn Sci
      2014, 5:693-703. doi: 10.1002/wcs.1322 For further resources related to this
      article, please visit the WIREs website. CONFLICT OF INTEREST: The authors have
      declared no conflicts of interest for this article.

PMID- 26308876
TI  - Association of Vitamin D Status and Clinical Outcome in Dogs with a Chronic
      Enteropathy.
AB  - BACKGROUND: Dogs with a chronic enteropathy (CE) have a lower vitamin D status,
      than do healthy dogs. Vitamin D status has been associated with a negative
      clinical outcome in humans with inflammatory bowel disease. OBJECTIVES: To
      examine the relationship between serum 25 hydroxyvitamin D (25(OH)D)
      concentrations at diagnosis and clinical outcome in dogs with a CE. ANIMALS:
      Forty-one dogs diagnosed with CE admitted to the Royal Dick School of Veterinary
      Studies, Hospital for Small Animals between 2007 and 2013. METHODS: Retrospective
      review. Serum 25(OH)D concentrations were compared between dogs which were alive
      at follow up or had died because of non-CE-related reasons (survivors) and dogs
      which died or were euthanized due to their CE (non-survivors). A binary logistic
      regression analysis was performed to determine significant predictors of death in
      dogs with CE. RESULTS: Serum concentrations of 25(OH)D at the time a CE was
      diagnosed were significantly lower in nonsurvivors (n = 15) (median nonsurvivors
      4.36 ng/mL, interquartile range 1.6-17.0 ng/mL), median survivors (n = 26) (24.9
      ng/mL interquartile range 15.63-39.45 ng/mL, P < .001). Serum 25(OH)D
      concentration was a significant predictor of death in dogs with CE (odds ratio
      1.08 [95% CI 1.02-1.18)]). CONCLUSIONS: Serum 25(OH)D concentrations at diagnosis
      are predictive of outcome in dogs with CE. The role of vitamin D in the
      initiation and outcome of chronic enteropathies in dogs is deserving of further
      study.

PMID- 26308877
TI  - Batch Statistical Process Monitoring Approach to a Cocrystallization Process.
AB  - Cocrystals are defined as crystalline structures composed of two or more
      compounds that are solid at room temperature held together by noncovalent bonds.
      Their main advantages are the increase of solubility, bioavailability,
      permeability, stability, and at the same time retaining active pharmaceutical
      ingredient bioactivity. The cocrystallization between furosemide and nicotinamide
      by solvent evaporation was monitored on-line using near-infrared spectroscopy
      (NIRS) as a process analytical technology tool. The near-infrared spectra were
      analyzed using principal component analysis. Batch statistical process monitoring
      was used to create control charts to perceive the process trajectory and define
      control limits. Normal and non-normal operating condition batches were performed
      and monitored with NIRS. The use of NIRS associated with batch statistical
      process models allowed the detection of abnormal variations in critical process
      parameters, like the amount of solvent or amount of initial components present in
      the cocrystallization.

PMID- 26308878
TI  - Clinical outcome of titanium-nitride-oxide-coated cobalt-chromium stents in
      patients with de novo coronary lesions: 12-month results of the OPTIMAX first-in
      man study.
AB  - OBJECTIVES: We explored the 12-month clinical outcome of the titanium-nitride
      oxide-coated OPTIMAX stent based on cobalt-chromium platform. BACKGROUND: The
      OPTIMAX stent demonstrated a satisfactory 6-month clinical outcome in de novo
      coronary lesions. METHODS: We enrolled 224 consecutive symptomatic patients with
      significant (50%) stenosis in de novo coronary lesions, who were treated with
      OPTIMAX stent implantation. The primary endpoint was major adverse cardiac events
      at 12-month follow-up, defined as a composite of cardiac death, non-fatal
      myocardial infarction (MI), or ischemia-driven target lesion revascularization
      (TLR). Stent thrombosis was adjudicated according to the definition of the
      Academic Research Consortium. RESULTS: The mean age of the cohort was 67 +/- 8
      years (75% males). Patients presented with acute coronary syndrome in 62.1%.
      Radial access was used in 92%; complex (type B and C) lesions were treated in
      79.9%. Both procedural and clinical success occurred in 100% of the cases. The
      mean follow-up period was 366 +/- 22 days. At 12-month follow-up, the primary
      endpoint occurred in 14 (6.3%) patients. Cardiac death occurred in three (1.3%)
      patients, non-fatal MI in seven (3.1%) patients, and ischemia-driven TLR in seven
      (3.1%) patients. No definite stent thrombosis occurred. CONCLUSIONS: In the
      current prospective observational study, implantation of the OPTIMAX stent
      demonstrated an adequate 12-month clinical outcome, with a low rate of major
      adverse cardiac events, and no stent thrombosis.

PMID- 26308879
TI  - Synthesis of Epitaxial Single-Layer MoS2 on Au(111).
AB  - We present a method for synthesizing large area epitaxial single-layer MoS2 on
      the Au(111) surface in ultrahigh vacuum. Using scanning tunneling microscopy and
      low energy electron diffraction, the evolution of the growth is followed from
      nanoscale single-layer MoS2 islands to a continuous MoS2 layer. An exceptionally
      good control over the MoS2 coverage is maintained using an approach based on
      cycles of Mo evaporation and sulfurization to first nucleate the MoS2 nanoislands
      and then gradually increase their size. During this growth process the native
      herringbone reconstruction of Au(111) is lifted as shown by low energy electron
      diffraction measurements. Within the MoS2 islands, we identify domains rotated by
      60 degrees  that lead to atomically sharp line defects at domain boundaries. As
      the MoS2 coverage approaches the limit of a complete single layer, the formation
      of bilayer MoS2 islands is initiated. Angle-resolved photoemission spectroscopy
      measurements of both single and bilayer MoS2 samples show a dramatic change in
      their band structure around the center of the Brillouin zone. Brief exposure to
      air after removing the MoS2 layer from vacuum is not found to affect its quality.

PMID- 26308880
TI  - Melatonin suppresses activation of hepatic stellate cells through RORalpha
      mediated inhibition of 5-lipoxygenase.
AB  - Liver fibrosis is scar tissue resulting from an uncontrolled wound-healing
      process in response to chronic liver injury. Liver damage generates an
      inflammatory reaction that activates hepatic stellate cells (HSC) that
      transdifferentiate from quiescent cells that control retinol metabolism to
      proliferative and migratory myofibroblasts that produce excessive amounts of
      extracellular matrix proteins, in particular collagen 1a1 (COL1A1). Although
      liver fibrosis is reversible, no effective drug therapy is available to prevent
      or reverse HSC activation. Melatonin has potent hepatoprotective properties in a
      variety of acute and chronic liver injury models and suppresses liver fibrosis.
      However, it remains unclear whether melatonin acts indirectly or directly on HSC
      to prevent liver fibrosis. Here, we studied the effect of melatonin on culture
      activated rat HSC. Melatonin dose-dependently suppressed the expression of HSC
      activation markers Col1a1 and alpha-smooth muscle actin (alphaSMA, Acta2), as
      well as HSC proliferation and loss of lipid droplets. The nuclear melatonin
      sensor retinoic acid receptor-related orphan receptor-alpha (RORalpha/Nr1f1) was
      expressed in quiescent and activated HSC, while the membranous melatonin
      receptors (Mtrn1a and Mtrn1b) were not. The synthetic RORalpha agonist SR1078
      more potently suppressed Col1a1 and alphaSma expression, HSC proliferation, and
      lipid droplet loss, while the RORalpha antagonist SR1001 blocked the antifibrotic
      features of melatonin. Melatonin and SR1078 inhibited the expression of Alox5,
      encoding 5-lipoxygenase (5-LO). The pharmacological 5-LO inhibitor AA861 reduced
      Acta2 and Col1a1 expression in activated HSC. We conclude that melatonin directly
      suppresses HSC activation via RORalpha-mediated inhibition of Alox5 expression,
      which provides novel drug targets to treat liver fibrosis. 

PMID- 26308881
TI  - Field Guide to Challenges and Opportunities in Antibody-Drug Conjugates for
      Chemists.
AB  - Antibody-drug conjugates have attracted a great amount of attention as a
      therapeutic strategy for diseases where targeting specific tissues and cells are
      critical components, such as in cancer therapy. Although promising, the number of
      approved ADC drugs is relatively limited. This emanates from the challenges
      associated with generating the conjugates and the complexities associated with
      the stability requirements for these conjugates during circulation and after
      reaching the target. Here, we provide a comprehensive overview of the design
      challenges facing the ADC field. These challenges also provide several unique
      research and development opportunities, which are also highlighted throughout the
      review. 

PMID- 26308882
TI  - Virological failure in two patients with HIV-1 RNA viral loads >1,000,000
      copies/ml initiated on elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil
      fumarate.
AB  - Very high baseline HIV-1 RNA viral loads require potent and robust antiretroviral
      regimens to achieve virological suppression. The coformulated single tablet
      regimen of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate
      (EVG/COBI/FTC/TDF) is recommended by the US Department of Health and Human
      Services for the treatment of HIV-1 in treatment-naive adults and adolescents
      regardless of baseline CD4(+) T-cell count and viral load. We report two cases of
      HIV-infected, treatment-naive patients, with baseline HIV-1 RNA viral loads
      >1,000,000 copies/ml who were initiated on the single tablet regimen
      EVG/COBI/FTC/TDF, but failed to attain viral load suppression and developed
      resistance to the components of EVG/COBI/FTC/TDF.

PMID- 26308884
TI  - Dynamics and Stabilization of the Human Gut Microbiome during the First Year of
      Life.

PMID- 26308883
TI  - Shared Predisposition in the Association Between Cannabis Use and Subcortical
      Brain Structure.
AB  - IMPORTANCE: Prior neuroimaging studies have suggested that alterations in brain
      structure may be a consequence of cannabis use. Siblings discordant for cannabis
      use offer an opportunity to use cross-sectional data to disentangle such causal
      hypotheses from shared effects of genetics and familial environment on brain
      structure and cannabis use. OBJECTIVES: To determine whether cannabis use is
      associated with differences in brain structure in a large sample of
      twins/siblings and to examine sibling pairs discordant for cannabis use to
      separate potential causal and predispositional factors linking lifetime cannabis
      exposure to volumetric alterations. DESIGN, SETTING, AND PARTICIPANTS: Cross
      sectional diagnostic interview, behavioral, and neuroimaging data were collected
      from community sampling and established family registries from August 2012 to
      September 2014. This study included data from 483 participants (22-35 years old)
      enrolled in the ongoing Human Connectome Project, with 262 participants reporting
      cannabis exposure (ie, ever used cannabis in their lifetime). MAIN OUTCOMES AND
      MEASURES: Cannabis exposure was measured with the Semi-Structured Assessment for
      the Genetics of Alcoholism. Whole-brain, hippocampus, amygdala, ventral striatum,
      and orbitofrontal cortex volumes were related to lifetime cannabis use (ever
      used, age at onset, and frequency of use) using linear regressions. Genetic
      (rhog) and environmental (rhoe) correlations between cannabis use and brain
      volumes were estimated. Linear mixed models were used to examine volume
      differences in sex-matched concordant unexposed (n = 71 pairs), exposed (n = 81
      pairs), or exposure discordant (n = 89 pairs) sibling pairs. RESULTS: Among 483
      study participants, cannabis exposure was related to smaller left amygdala
      (approximately 2.3%; P = .007) and right ventral striatum (approximately 3.5%; P
      < .005) volumes. These volumetric differences were within the range of normal
      variation. The association between left amygdala volume and cannabis use was
      largely owing to shared genetic factors (rhog = -0.43; P = .004), while the
      origin of the association with right ventral striatum volumes was unclear.
      Importantly, brain volumes did not differ between sex-matched siblings discordant
      for use (fixed effect = -7.43; t = -0.93, P = .35). Both the exposed and
      unexposed siblings in pairs discordant for cannabis exposure showed reduced
      amygdala volumes relative to members of concordant unexposed pairs (fixed effect
      = 12.56; t = 2.97; P = .003). CONCLUSIONS AND RELEVANCE: In this study,
      differences in amygdala volume in cannabis users were attributable to common
      predispositional factors, genetic or environmental in origin, with little support
      for causal influences. Causal influences, in isolation or in conjunction with
      predispositional factors, may exist for other brain regions (eg, ventral
      striatum) or at more severe levels of cannabis involvement and deserve further
      study.

PMID- 26308887
TI  - Symmetrically Related Construction and Optical Properties of Two
      Noncentrosymmetric 3D Iodides of d(10) Cation (Cu(+), Ag(+)) Based on the N
      Benzylpyridinium and Its Supramolecular Interactions.
AB  - Two noncentrosymmetric compounds, namely, [N-Bz-Py]2[Cu6I8] (1) and [N-Bz
      Py]4[Ag9I13] (2) (N-Bz-Py(+) = N-benzylpyridinium), with three-dimensional open
      frameworks, were synthesized solvothermally via in situ benzylation of pyridine.
      1 is constructed from 3-connected Cu3I7 secondary building units (SBUs) with
      chiral (10,3)-a topology, while the occluded N-Bz-Py(+) forms a complementary
      supramolecular (10,3)-a net via pi-pi interactions. 2 is characteristic of
      acentric connections of trimeric Ag3I8 and hexamer Ag6I12 SBU, while N-Bz-Py(+)
      in the channels aggregates into asymmetrically supramolecular chains via pi-pi
      interactions. Remarkable structural correlations imply the unique amplification
      and transfer of asymmetric information from V-shaped N-Bz-Py(+) to organic
      supramolecular nets and inorganic frameworks, which are confirmed by their second
      harmonic generation responses. Adsorption spectra reveal their semiconductive
      nature (2.52 eV for 1 and 3.02 eV for 2) and interesting reversible
      thermochromism for 1 based on the intermolecular charge transfer. 

PMID- 26308886
TI  - Polysaccharides of Trametes versicolor Improve Bone Properties in Diabetic Rats.
AB  - This study investigates the effects of Trametes versicolor (L.:Fr.) Pilat (TVP,
      also known as Yunzhi) on bone properties in diabetic rats. Forty-five male Wistar
      rats (8 weeks old) were fed either a chow diet (control) or a high-fat diet
      throughout the study period of 28 days. Animals in the high-fat-diet group were
      injected with nicotinamide and streptozotocin to induce diabetes mellitus (DM).
      The DM rats were divided into a group receiving distilled water (vehicle) and
      another group receiving TVP at 0.1 g/kg weight by gavage. Relative to the vehicle
      group, TVP gavage lowered postprandial blood sugar (225 +/- 18 mg/dL for TVP vs
      292 +/- 15 mg/dL for vehicle, p < 0.001) on day 26. Compared to the vehicle
      group, TVP mitigated DM-induced bone deterioration as determined by increasing
      bone volume of proximal tibia (22.8 +/- 1.4% for TVP vs 16.8 +/- 1.3% for
      vehicle, p = 0.003), trabecular number (p = 0.011), and femoral bone strength
      (11% in maximal load, 22% in stiffness, 14% in modulus, p < 0.001), and by
      reducing loss of femoral cortical porosity by 25% (p < 0.001). Our study
      demonstrates the protective effect of TVP on bone properties was mediated
      through, in part, the improvement of hyperglycemic control in DM animals. 

PMID- 26308885
TI  - Long-term follow-up of a phase 2 study of chemotherapy plus dasatinib for the
      initial treatment of patients with Philadelphia chromosome-positive acute
      lymphoblastic leukemia.
AB  - BACKGROUND: The long-term efficacy of a combination of chemotherapy and dasatinib
      in patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic
      leukemia (ALL) is not well established. METHODS: Patients received dasatinib with
      8 cycles of alternating hyperfractionated cyclophosphamide, vincristine,
      doxorubicin, and dexamethasone and high-dose cytarabine and methotrexate.
      Patients in complete remission (CR) continued maintenance dasatinib, vincristine,
      and prednisone for 2 years, which was followed by dasatinib indefinitely.
      Patients eligible for allogeneic stem cell transplantation (SCT) received it
      during their first CR. RESULTS: Seventy-two patients with a median age of 55
      years (range, 21-80 years) were treated; 69 (96%) achieved CR. Among them, 57
      (83%) achieved cytogenetic CR after 1 cycle, and 64 (93%) achieved a major
      molecular response at a median of 4 weeks (range, 2-38 weeks). Sixty-five
      patients (94%) were negative for minimal residual disease assessed by flow
      cytometry at a median of 3 weeks (range, 2-37 weeks). Dasatinib-related grade 3
      and 4 adverse events included bleeding, pleural/pericardial effusions, and
      elevated transaminases. With a median follow-up of 67 months (range, 33-97
      months), 33 patients (46%) were alive, and 30 (43%) were in CR; 12 underwent
      allogeneic SCT. Thirty-nine patients died (3 at induction, 19 after relapse, 7
      after SCT performed during first CR, and 10 during CR). The median disease-free
      survival and overall survival were 31 (range, 0.3-97 months) and 47 months
      (range, 0.2-97 months), respectively. Seven relapsed patients had BCR-ABL kinase
      domain mutations, including 4 with T315I. CONCLUSIONS: A combination of
      chemotherapy with dasatinib is effective in achieving long-term remission for
      patients with newly diagnosed Ph + ALL.

PMID- 26308888
TI  - History taking by physiotherapists with low back pain patients: are illness
      perceptions addressed properly?
AB  - PURPOSE: Despite the increasing evidence that illness perceptions should be
      addressed in patients, there is a lack of studies evaluating whether
      physiotherapists question illness perceptions. This study, using a mixed-methods
      design, investigates the integration of illness perceptions during the first
      consultation of physiotherapists treating patients with low back pain (LBP).
      METHODS: Thirty-four physiotherapists performed usual history taking in a patient
      with non-specific LBP. The interview was audiotaped and illness perceptions were
      indexed using an observational instrument, based on the domains of Leventhal's
      Common Sense Model. Patients were also asked to fill in the Illness Perception
      Questionnaire-Revised for LBP. RESULTS: Physiotherapists assessed the illness
      identity, also perceptions regarding the (physical) cause and controllability of
      LBP were evaluated. Illness perceptions, such as timeline, consequences,
      coherence and emotional representation, were poorly assessed. Results of the
      questionnaire reveal that LBP-patients report overuse, workload and bad posture
      as primary cause. Patients held positive beliefs about the controllability and
      have high illness coherence. CONCLUSION: Belgian physiotherapists mainly question
      bio-medically oriented illness perceptions, e.g. physical symptoms and causes,
      but do not sufficiently address psychosocially oriented illness perceptions as
      recommended in LBP guidelines. IMPLICATIONS FOR REHABILITATION: Belgian
      physiotherapists mainly question biomedical oriented illness perceptions (illness
      identity, provoking factors and treatment control) in patients with low back pain
      (LBP) during the history taking (i.e. the first consultation). From a bio-psycho
      social view psychosocially oriented illness perceptions should be incorporated in
      the daily routine of physiotherapist's to comply with the bio-psycho-social
      treatment guidelines for LBP. Continuing education is mandatory in order to
      improve physiotherapists' knowledge regarding the use of all dimensions of
      illness perceptions in the assessment of patients with LBP.

PMID- 26308889
TI  - Orientation-specific joining of AID-initiated DNA breaks promotes antibody class
      switching.
AB  - During B-cell development, RAG endonuclease cleaves immunoglobulin heavy chain
      (IgH) V, D, and J gene segments and orchestrates their fusion as deletional
      events that assemble a V(D)J exon in the same transcriptional orientation as
      adjacent CMU constant region exons. In mice, six additional sets of constant
      region exons (CHs) lie 100-200 kilobases downstream in the same transcriptional
      orientation as V(D)J and CMU exons. Long repetitive switch (S) regions precede
      CMU and downstream CHs. In mature B cells, class switch recombination (CSR)
      generates different antibody classes by replacing CMU with a downstream CH (ref.
      2). Activation-induced cytidine deaminase (AID) initiates CSR by promoting
      deamination lesions within SMU and a downstream acceptor S region; these lesions
      are converted into DNA double-strand breaks (DSBs) by general DNA repair factors.
      Productive CSR must occur in a deletional orientation by joining the upstream end
      of an SMU DSB to the downstream end of an acceptor S-region DSB. However, the
      relative frequency of deletional to inversional CSR junctions has not been
      measured. Thus, whether orientation-specific joining is a programmed mechanistic
      feature of CSR as it is for V(D)J recombination and, if so, how this is achieved
      is unknown. To address this question, we adapt high-throughput genome-wide
      translocation sequencing into a highly sensitive DSB end-joining assay and apply
      it to endogenous AID-initiated S-region DSBs in mouse B cells. We show that CSR
      is programmed to occur in a productive deletional orientation and does so via an
      unprecedented mechanism that involves in cis Igh organizational features in
      combination with frequent S-region DSBs initiated by AID. We further implicate
      ATM-dependent DSB-response factors in enforcing this mechanism and provide an
      explanation of why CSR is so reliant on the 53BP1 DSB-response factor. 

PMID- 26308890
TI  - Cancer: A moving target.

PMID- 26308892
TI  - Molecular biology: Unequal opportunity during class switching.

PMID- 26308891
TI  - The C9orf72 repeat expansion disrupts nucleocytoplasmic transport.
AB  - The hexanucleotide repeat expansion (HRE) GGGGCC (G4C2) in C9orf72 is the most
      common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia
      (FTD). Recent studies support an HRE RNA gain-of-function mechanism of
      neurotoxicity, and we previously identified protein interactors for the G4C2 RNA
      including RanGAP1. A candidate-based genetic screen in Drosophila expressing 30
      G4C2 repeats identified RanGAP (Drosophila orthologue of human RanGAP1), a key
      regulator of nucleocytoplasmic transport, as a potent suppressor of
      neurodegeneration. Enhancing nuclear import or suppressing nuclear export of
      proteins also suppresses neurodegeneration. RanGAP physically interacts with HRE
      RNA and is mislocalized in HRE-expressing flies, neurons from C9orf72 ALS patient
      derived induced pluripotent stem cells (iPSC-derived neurons), and in C9orf72 ALS
      patient brain tissue. Nuclear import is impaired as a result of HRE expression in
      the fly model and in C9orf72 iPSC-derived neurons, and these deficits are rescued
      by small molecules and antisense oligonucleotides targeting the HRE G
      quadruplexes. Nucleocytoplasmic transport defects may be a fundamental pathway
      for ALS and FTD that is amenable to pharmacotherapeutic intervention. 

PMID- 26308893
TI  - A spatial model predicts that dispersal and cell turnover limit intratumour
      heterogeneity.
AB  - Most cancers in humans are large, measuring centimetres in diameter, and composed
      of many billions of cells. An equivalent mass of normal cells would be highly
      heterogeneous as a result of the mutations that occur during each cell division.
      What is remarkable about cancers is that virtually every neoplastic cell within a
      large tumour often contains the same core set of genetic alterations, with
      heterogeneity confined to mutations that emerge late during tumour growth. How
      such alterations expand within the spatially constrained three-dimensional
      architecture of a tumour, and come to dominate a large, pre-existing lesion, has
      been unclear. Here we describe a model for tumour evolution that shows how short
      range dispersal and cell turnover can account for rapid cell mixing inside the
      tumour. We show that even a small selective advantage of a single cell within a
      large tumour allows the descendants of that cell to replace the precursor mass in
      a clinically relevant time frame. We also demonstrate that the same mechanisms
      can be responsible for the rapid onset of resistance to chemotherapy. Our model
      not only provides insights into spatial and temporal aspects of tumour growth,
      but also suggests that targeting short-range cellular migratory activity could
      have marked effects on tumour growth rates. 

PMID- 26308894
TI  - Corrigendum: Lanosterol reverses protein aggregation in cataracts.

PMID- 26308895
TI  - Alcohols as alkylating agents in heteroarene C-H functionalization.
AB  - Redox processes and radical intermediates are found in many biochemical
      processes, including deoxyribonucleotide synthesis and oxidative DNA damage. One
      of the core principles underlying DNA biosynthesis is the radical-mediated
      elimination of H2O to deoxygenate ribonucleotides, an example of 'spin-centre
      shift', during which an alcohol C-O bond is cleaved, resulting in a carbon
      centred radical intermediate. Although spin-centre shift is a well-understood
      biochemical process, it is underused by the synthetic organic chemistry
      community. We wondered whether it would be possible to take advantage of this
      naturally occurring process to accomplish mild, non-traditional alkylation
      reactions using alcohols as radical precursors. Because conventional radical
      based alkylation methods require the use of stoichiometric oxidants, increased
      temperatures or peroxides, a mild protocol using simple and abundant alkylating
      agents would have considerable use in the synthesis of diversely functionalized
      pharmacophores. Here we describe the development of a dual catalytic alkylation
      of heteroarenes, using alcohols as mild alkylating reagents. This method
      represents the first, to our knowledge, broadly applicable use of unactivated
      alcohols as latent alkylating reagents, achieved via the successful merger of
      photoredox and hydrogen atom transfer catalysis. The value of this multi
      catalytic protocol has been demonstrated through the late-stage functionalization
      of the medicinal agents, fasudil and milrinone. 

PMID- 26308896
TI  - Neurodegeneration: Problems at the nuclear pore.

PMID- 26308897
TI  - Integrator mediates the biogenesis of enhancer RNAs.
AB  - Integrator is a multi-subunit complex stably associated with the carboxy-terminal
      domain (CTD) of RNA polymerase II (RNAPII). Integrator is endowed with a core
      catalytic RNA endonuclease activity, which is required for the 3'-end processing
      of non-polyadenylated, RNAPII-dependent, uridylate-rich, small nuclear RNA genes.
      Here we examine the requirement of Integrator in the biogenesis of transcripts
      derived from distal regulatory elements (enhancers) involved in tissue- and
      temporal-specific regulation of gene expression in metazoans. Integrator is
      recruited to enhancers and super-enhancers in a stimulus-dependent manner.
      Functional depletion of Integrator subunits diminishes the signal-dependent
      induction of enhancer RNAs (eRNAs) and abrogates stimulus-induced enhancer
      promoter chromatin looping. Global nuclear run-on and RNAPII profiling reveals a
      role for Integrator in 3'-end cleavage of eRNA primary transcripts leading to
      transcriptional termination. In the absence of Integrator, eRNAs remain bound to
      RNAPII and their primary transcripts accumulate. Notably, the induction of eRNAs
      and gene expression responsiveness requires the catalytic activity of Integrator
      complex. We propose a role for Integrator in biogenesis of eRNAs and enhancer
      function in metazoans. 

PMID- 26308898
TI  - Erratum: Genetic diversity and evolutionary dynamics of Ebola virus in Sierra
      Leone.

PMID- 26308899
TI  - GGGGCC repeat expansion in C9orf72 compromises nucleocytoplasmic transport.
AB  - The GGGGCC (G4C2) repeat expansion in a noncoding region of C9orf72 is the most
      common cause of sporadic and familial forms of amyotrophic lateral sclerosis and
      frontotemporal dementia. The basis for pathogenesis is unknown. To elucidate the
      consequences of G4C2 repeat expansion in a tractable genetic system, we generated
      transgenic fly lines expressing 8, 28 or 58 G4C2-repeat-containing transcripts
      that do not have a translation start site (AUG) but contain an open-reading frame
      for green fluorescent protein to detect repeat-associated non-AUG (RAN)
      translation. We show that these transgenic animals display dosage-dependent,
      repeat-length-dependent degeneration in neuronal tissues and RAN translation of
      dipeptide repeat (DPR) proteins, as observed in patients with C9orf72-related
      disease. This model was used in a large-scale, unbiased genetic screen,
      ultimately leading to the identification of 18 genetic modifiers that encode
      components of the nuclear pore complex (NPC), as well as the machinery that
      coordinates the export of nuclear RNA and the import of nuclear proteins.
      Consistent with these results, we found morphological abnormalities in the
      architecture of the nuclear envelope in cells expressing expanded G4C2 repeats in
      vitro and in vivo. Moreover, we identified a substantial defect in RNA export
      resulting in retention of RNA in the nuclei of Drosophila cells expressing
      expanded G4C2 repeats and also in mammalian cells, including aged induced
      pluripotent stem-cell-derived neurons from patients with C9orf72-related disease.
      These studies show that a primary consequence of G4C2 repeat expansion is the
      compromise of nucleocytoplasmic transport through the nuclear pore, revealing a
      novel mechanism of neurodegeneration. 

PMID- 26308900
TI  - A four-helix bundle stores copper for methane oxidation.
AB  - Methane-oxidizing bacteria (methanotrophs) require large quantities of copper for
      the membrane-bound (particulate) methane monooxygenase. Certain methanotrophs are
      also able to switch to using the iron-containing soluble methane monooxygenase to
      catalyse methane oxidation, with this switchover regulated by copper. Methane
      monooxygenases are nature's primary biological mechanism for suppressing
      atmospheric levels of methane, a potent greenhouse gas. Furthermore,
      methanotrophs and methane monooxygenases have enormous potential in
      bioremediation and for biotransformations producing bulk and fine chemicals, and
      in bioenergy, particularly considering increased methane availability from
      renewable sources and hydraulic fracturing of shale rock. Here we discover and
      characterize a novel copper storage protein (Csp1) from the methanotroph
      Methylosinus trichosporium OB3b that is exported from the cytosol, and stores
      copper for particulate methane monooxygenase. Csp1 is a tetramer of four-helix
      bundles with each monomer binding up to 13 Cu(I) ions in a previously unseen
      manner via mainly Cys residues that point into the core of the bundle. Csp1 is
      the first example of a protein that stores a metal within an established protein
      folding motif. This work provides a detailed insight into how methanotrophs
      accumulate copper for the oxidation of methane. Understanding this process is
      essential if the wide-ranging biotechnological applications of methanotrophs are
      to be realized. Cytosolic homologues of Csp1 are present in diverse bacteria,
      thus challenging the dogma that such organisms do not use copper in this
      location. 

PMID- 26308902
TI  - Valence Band Modification and High Thermoelectric Performance in SnTe Heavily
      Alloyed with MnTe.
AB  - We demonstrate a high solubility limit of >9 mol% for MnTe alloying in SnTe. The
      electrical conductivity of SnTe decreases gradually while the Seebeck coefficient
      increases remarkably with increasing MnTe content, leading to enhanced power
      factors. The room-temperature Seebeck coefficients of Mn-doped SnTe are
      significantly higher than those predicted by theoretical Pisarenko plots for pure
      SnTe, indicating a modified band structure. The high-temperature Hall data of Sn1
      xMnxTe show strong temperature dependence, suggestive of a two-valence-band
      conduction behavior. Moreover, the peak temperature of the Hall plot of Sn1
      xMnxTe shifts toward lower temperature as MnTe content is increased, which is
      clear evidence of decreased energy separation (band convergence) between the two
      valence bands. The first-principles electronic structure calculations based on
      density functional theory also support this point. The higher doping fraction
      (>9%) of Mn in comparison with ~3% for Cd and Hg in SnTe gives rise to a much
      better valence band convergence that is responsible for the observed highest
      Seebeck coefficient of ~230 MUV/K at 900 K. The high doping fraction of Mn in
      SnTe also creates stronger point defect scattering, which when combined with
      ubiquitous endotaxial MnTe nanostructures when the solubility of Mn is exceeded
      scatters a wide spectrum of phonons for a low lattice thermal conductivity of 0.9
      W m(-1) K(-1) at 800 K. The synergistic role that Mn plays in regulating the
      electron and phonon transport of SnTe yields a high thermoelectric figure of
      merit of 1.3 at 900 K. 

PMID- 26308901
TI  - Allosteric receptor activation by the plant peptide hormone phytosulfokine.
AB  - Phytosulfokine (PSK) is a disulfated pentapeptide that has a ubiquitous role in
      plant growth and development. PSK is perceived by its receptor PSKR, a leucine
      rich repeat receptor kinase (LRR-RK). The mechanisms underlying the recognition
      of PSK, the activation of PSKR and the identity of the components downstream of
      the initial binding remain elusive. Here we report the crystal structures of the
      extracellular LRR domain of PSKR in free, PSK- and co-receptor-bound forms. The
      structures reveal that PSK interacts mainly with a beta-strand from the island
      domain of PSKR, forming an anti-beta-sheet. The two sulfate moieties of PSK
      interact directly with PSKR, sensitizing PSKR recognition of PSK. Supported by
      biochemical, structural and genetic evidence, PSK binding enhances PSKR
      heterodimerization with the somatic embryogenesis receptor-like kinases (SERKs).
      However, PSK is not directly involved in PSKR-SERK interaction but stabilizes
      PSKR island domain for recruitment of a SERK. Our data reveal the structural
      basis for PSKR recognition of PSK and allosteric activation of PSKR by PSK,
      opening up new avenues for the design of PSKR-specific small molecules. 

PMID- 26308903
TI  - Achiral 2-Hydroxy Protecting Group for the Stereocontrolled Synthesis of 1,2-cis
      alpha-Glycosides by Six-Ring Neighboring Group Participation.
AB  - Glycosylation of a fully armed donor bearing a 2-O-(trimethoxybenzenethiol) ethyl
      ether protecting group is completely alpha-selective with a range of carbohydrate
      alcohol acceptors. Low-temperature NMR studies confirm the intermediacy of cyclic
      sulfonium ion intermediates arising from six-membered beta-sulfonium ring
      neighboring group participation. Selective protecting group removal is achieved
      in high yield in a single operation by S-methylation and base-induced beta
      elimination. 

PMID- 26308904
TI  - Sensation Seeking as a Moderator of Gain- and Loss-Framed HIV-Test Promotion
      Message Effects.
AB  - This study used an experiment (N = 504) to test whether the fit between sensation
      seeking disposition and frame enhances the persuasiveness of gain- and loss
      framed HIV test promotion messages. Gain- and loss-framed messages may be
      consistent with low and high sensation seekers' disposition with respect to risk
      behavior. We hypothesized that a loss-framed message would be more persuasive for
      high sensation seekers and that a gain-framed message should be more effective
      for low sensation seekers. We also expected elaboration to mediate the
      interaction. Results demonstrated the hypothesized interaction. When the message
      frame fit with the viewer's way of thinking, the persuasive power of the message
      was enhanced. The mediation hypothesis was not supported. Practical implications
      for targeting and message design are discussed.

PMID- 26308905
TI  - Effect of Hydrophobic Chain Structure on Phase Transition and Domain Formation of
      Hybrid Alcohol Films Adsorbed at the Hexane/Water Interface.
AB  - The phase transition and domain formation of the adsorbed film of two kinds of
      hybrid alcohols (CF3(CF2)m-1(CH2)nOH, FmHnOH), 2-perfluorooctylethanol (F8H2OH)
      and 2-perfluorohexylhexanol (F6H6OH), as a mixture at the hexane/water interface
      was investigated by interfacial tensiometry and X-ray reflection. The interfacial
      tension gamma versus total molality m curve of pure F8H2OH has a break point at
      high concentration, and thus, the mean area per molecule A changes
      discontinuously at high interfacial pressure pi, corresponding to the phase
      transition between expanded and condensed films. The Fresnel divided reflectivity
      R/RF versus Qz plots in the expanded state was well-fitted by the domain model
      for incoherent interference to determine the interfacial coverage, which is the
      fraction of the interface covered by the condensed phase. This indicates that the
      expanded film is heterogeneous and consists of a condensed F8H2OH domain, the
      size of which is larger than the X-ray coherence length (~5 MUm). In the mixed
      system, the discontinuous change in A at the phase transition point becomes small
      with increasing the bulk composition of F6H6OH X2 in the mixture, and eventually
      the A value changes continuously; i.e, the phase transition becomes obscure in X2
      >= 0.6. This behavior was linked to an increase in interfacial coverage with X2.
      Furthermore, the R/RF versus Qz plot was fitted by the domain model for coherent
      interference, suggesting that the size of the domain is smaller than 5 MUm. These
      results are probably due to the reduction of domain line tension by preferential
      adsorption of F6H6OH at the F8H2OH domain boundary. 

PMID- 26308908
TI  - Classic Studies on the Potential of Stem Cell Neuroregeneration.
AB  - The 1990s and 2000s were the beginning of an exciting time period for
      developmental neuroscience and neural stem cell research. By better understanding
      brain plasticity and the birth of new neurons in the adult brain, contrary to
      established dogma, hope for therapy from devastating neurological diseases was
      generated. The potential for stem cells to provide functional recovery in humans
      remains to be further tested and to further move into the clinical trial realm.
      The future certainly has great promise on stem cells to assist in alleviation of
      difficult-to-treat neurologic disorders. This article reviews classic studies of
      the 1990s and 2000s that paved the way for the advances of today, which can in
      turn lead to tomorrow's therapies. 

PMID- 26308909
TI  - Is Botox for anal pain an effective treatment option?
AB  - PURPOSE: The aim of this study was to evaluate the efficacy of Botulinum toxin-A
      (Botox) in relieving anal pain associated with anal fissure (AF) and Levator ani
      syndrome (LS). METHODS: All patients with medically refractory AF or LS from 2005
      to 2012 and treated with Botox injections were included. RESULTS: One hundred and
      three patients [66 patients (53 female) with AF and 37 patients (26 female) with
      LS] were evaluated. The minimum/maximum dose of Botox was 20/100 units for AF and
      50/200 units for LS. Thirteen (19.7%) patients with AF and 14 (38%) patients with
      LS received > 1 Botox treatment. The time interval between injections varied from
      1 to 12 months. Mean follow-up was 6.4 months for AF and 9 months for LS. Relief
      of anal pain was noted in 59% of AF and 43% of LS patients. Significant changes
      in pre- and post-op pain scores were noted in both groups. Nine out of 12
      patients with failed sphincterotomy were relieved after Botox treatment.
      Temporary fecal incontinence was reported in 2/66 (3%) AF patients and 4/37 (10%)
      of LS patients. Overall, 66% patients' recommended Botox treatment and 72% were
      happy with the treatment as per telephone interview results. CONCLUSION: Botox
      relieves pain more effectively in AF than in LS. It is an effective option in
      medically refractory cases of LS. Higher doses of Botox are safe to use in LS;
      however, this needs to be evaluated. Botox injections have an overall low
      complication rate.

PMID- 26308910
TI  - Activation of SphK1 by K6PC-5 Inhibits Oxygen-Glucose Deprivation/Reoxygenation
      Induced Myocardial Cell Death.
AB  - In the current study, we evaluated the potential effect of a novel sphingosine
      kinase 1 (SphK1) activator, K6PC-5, on oxygen-glucose deprivation
      (OGD)/reoxygenation-induced damages to myocardial cells. We demonstrated that
      K6PC-5 increased intracellular sphingosine-1-phosphate (S1P) content and
      remarkably inhibited OGD/reoxygenation-induced death of myocardial cells (H9c2/HL
      1 lines and primary murine myocardiocytes). SphK1 inhibitors, B-5354c and SKI-II,
      or SphK1-siRNA knockdown not only aggregated OGD/reoxygenation-induced
      cytotoxicity but also nullified the cytoprotection by K6PC-5. On the other hand,
      overexpression of SphK1 alleviated H9c2 cell death by OGD/reoxygenation, and K6PC
      5-mediated cytoprotection was also enhanced in SphK1 overexpressed cells.
      Molecularly, OGD/reoxygenation activated the mitochondrial death pathway,
      evidenced by reactive oxygen species (ROS) production, mitochondrial membrane
      potential reduction, and p53-cyclophilin D (Cyp-D) association, which were all
      alleviated by K6PC-5 or overexpression of SphK1, but exacerbated by SphK1
      knockdown. Furthermore, OGD/reoxygenation induced prodeath ceramide production in
      myocardial cells, which was largely suppressed by K6PC-5. In the meantime, adding
      a cell-permeable short-chain ceramide (C6) mimicked OGD/reoxygenation actions and
      induced ROS production and the mitochondrial death pathway in myocardial cells.
      Together, we conclude that K6PC-5 inhibits OGD/reoxygenation-induced myocardial
      cell death probably through activating SphK1. The results of the study indicate a
      potential benefit of K6PC-5 on ischemic heart disease. 

PMID- 26308911
TI  - Clearance of Hepatitis C Virus Improves Insulin Resistance During and After
      Peginterferon and Ribavirin Therapy.
AB  - Patients with chronic hepatitis C virus (HCV) infection are at a greater risk of
      developing insulin resistance (IR). However, little is known about when insulin
      sensitivity may improve during or after treatment for hepatitis C. In this study,
      we examined the effect of combination therapy with pegylated interferon-alpha and
      ribavirin on IR in patients with chronic HCV infection. We also analyzed factors
      associated with changes in insulin sensitivity. IR was estimated by homeostasis
      model assessment (HOMA-IR). HOMA-IR was measured before therapy, during therapy
      (12 and 24 weeks), and at the end of therapy (EOT; 24 or 48 weeks). We analyzed
      78 HCV patients receiving combination therapy. Twenty-two patients (28.2%)
      exhibited pretreatment IR (HOMA-IR >2.5). In all patients, HOMA-IR was not
      significantly different from baseline values at 12 weeks (P = 0.823), 24 weeks (P
      = 0.417), or at EOT (P = 0.158). In patients with pretreatment IR, a significant
      decrease in HOMA-IR was observed at 12 weeks (P = 0.023), 24 weeks (P = 0.008),
      and at EOT (P = 0.002). Multivariate analysis using a logistic regression model
      showed that baseline HOMA-IR is the only factor associated with the decline in
      HOMA-IR during and after therapy. The eradication of HCV infection was associated
      with improved insulin sensitivity among patients with pretreatment IR. This
      significant improvement in insulin sensitivity may occur as early as 12 weeks
      after the initiation of antiviral therapy.

PMID- 26308912
TI  - Reviewing current and emerging antiemetics for chemotherapy-induced nausea and
      vomiting prophylaxis.
AB  - This review provides background information on chemotherapy-induced nausea and
      vomiting (CINV) classification and pathophysiology and reviews various antiemetic
      agents for CINV prophylaxis, including corticosteroids, serotonin receptor
      antagonists (5-HT3 RAs), tachykinin NK1 receptor antagonists (NK1 RAs), and
      olanzapine. Other less commonly used agents are briefly discussed. Practical
      considerations are reviewed as well, including emetogenicity of chemotherapeutic
      regimens, patient-specific risk factors for CINV, principles of CINV management,
      health economics outcome research, and quality of life. Available data on the
      newly FDA-approved antiemetic combination netupitant/palonosetron (NEPA) is also
      reviewed. Prevention of CINV is an important goal in managing patients with
      cancer and is especially difficult with respect to nausea and delayed CINV.
      Corticosteroids are a mainstay of CINV prophylaxis and are usually given in
      combination with other therapies. The 5-HT3 RA palonosetron has shown increased
      efficacy over other agents in the same class for prevention of delayed emesis
      with moderately emetogenic chemotherapy and NK1 RAs improve emesis prevention in
      combination with 5-HT3 RAs and dexamethasone. Olanzapine has shown efficacy for
      CINV prophylaxis and the treatment of breakthrough CINV. The new combination
      therapy, NEPA, has been shown to be efficacious for the prevention of acute,
      delayed, and overall CINV. Risk factors that have been identified for CINV
      include gender, age, and alcohol intake. It is important to assess the
      emetogenicity of chemotherapy regimens as well as the potential impact of patient
      risk factors in order to provide adequate prophylaxis. Acute and delayed CINV are
      severe, burdensome side effects of chemotherapy; however, new data on prevention
      and the discovery of new agents can further improve CINV control. 

PMID- 26308913
TI  - [Mediastinal primary amyloidosis of pseudo tumor appearance].

PMID- 26308914
TI  - The Role of a Novel TRMT1 Gene Mutation and Rare GRM1 Gene Defect in Intellectual
      Disability in Two Azeri Families.
AB  - Cognitive impairment or intellectual disability (ID) is a widespread
      neurodevelopmental disorder characterized by low IQ (below 70). ID is genetically
      heterogeneous and is estimated to affect 1-3% of the world's population. In
      affected children from consanguineous families, autosomal recessive inheritance
      is common, and identifying the underlying genetic cause is an important issue in
      clinical genetics. In the framework of a larger project, aimed at identifying
      candidate genes for autosomal recessive intellectual disorder (ARID), we recently
      carried out single nucleotide polymorphism-based genome-wide linkage analysis in
      several families from Ardabil province in Iran. The identification of
      homozygosity-by-descent loci in these families, in combination with whole exome
      sequencing, led us to identify possible causative homozygous changes in two
      families. In the first family, a missense variant was found in GRM1 gene, while
      in the second family, a frameshift alteration was identified in TRMT1, both of
      which were found to co-segregate with the disease. GRM1, a known causal gene for
      autosomal recessive spinocerebellar ataxia (SCAR13, MIM#614831), encodes the
      metabotropic glutamate receptor1 (mGluR1). This gene plays an important role in
      synaptic plasticity and cerebellar development. Conversely, the TRMT1 gene
      encodes a tRNA methyltransferase that dimethylates a single guanine residue at
      position 26 of most tRNAs using S-adenosyl methionine as the methyl group donor.
      We recently presented TRMT1 as a candidate gene for ARID in a consanguineous
      Iranian family (Najmabadi et al., 2011). We believe that this second Iranian
      family with a biallelic loss-of-function mutation in TRMT1 gene supports the idea
      that this gene likely has function in development of the disorder. 

PMID- 26308915
TI  - Sun-Compass Orientation in Mediterranean Fish Larvae.
AB  - Mortality is very high during the pelagic larval phase of fishes but the factors
      that determine recruitment success remain unclear and hard to predict. Because of
      their bipartite life history, larvae of coastal species have to head back to the
      shore at the end of their pelagic episode, to settle. These settlement-stage
      larvae are known to display strong sensory and motile abilities, but most work
      has been focused on tropical, insular environments and on the influence of coast
      related cues on orientation. In this study we quantified the in situ orientation
      behavior of settlement-stage larvae in a temperate region, with a continuous
      coast and a dominant along-shore current, and inspected both coast-dependent and
      independent cues. We tested six species: one Pomacentridae, Chromis chromis, and
      five Sparidae, Boops boops, Diplodus annularis, Oblada melanura, Spicara smaris
      and Spondyliosoma cantharus. Over 85% of larvae were highly capable of keeping a
      bearing, which is comparable to the orientation abilities of tropical species.
      Sun-related cues influenced the precision of bearing-keeping at individual level.
      Three species, out of the four tested in sufficient numbers, oriented
      significantly relative to the sun position. These are the first in situ
      observations demonstrating the use of a sun compass for orientation by wild
      caught settlement-stage larvae. This mechanism has potential for large-scale
      orientation of fish larvae globally. 

PMID- 26308916
TI  - Chemical Composition and In Vitro Cytotoxicity of Essential Oils from Leaves and
      Flowers of Callistemon citrinus from Western Himalayas.
AB  - BACKGROUND: Plant-based traditional system of medicine continues to play an
      important role in healthcare. In order to find new potent source of bioactive
      molecules, we studied the cytotoxic activity of the essential oils from the
      flowers and leaves of Callistemon citrinus. This is the first report on
      anticancer potential of essential oils of C. citrinus. METHODS: Cytotoxicity of
      essential oil was evaluated using sulfo-rhodamine B (SRB) assay against human
      lung carcinoma (A549), rat glioma (C-6), human colon cancer (Colo-205) and human
      cervical cancer (SiHa) cells. Apoptosis induction was evaluated by caspase-3/7
      activity which was further confirmed by western blotting. Percentage cell
      apoptosis was determined by Annexin V based dead cell assay followed by DNA
      content as cell cycle analysis against A549 and C-6 cells. While 3-(4,5
      dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to
      check the toxicity against normal human peripheral blood mononuclear cells
      (PBMCs), the immunomodulatory activity on mouse splenocytes was evaluated using
      SRB assay. RESULTS: The GC and GC-MS analysis of these essential oils revealed
      high content of alpha-pinene (32.3%), limonene (13.1%) and alpha-terpineol
      (14.6%) in leaf sample, whereas the flower oil was dominated by 1,8-cineole
      (36.6%) followed by alpha-pinene (29.7%). The leaf oil contained higher amount of
      monoterpene hydrocarbons (52.1%) and sesquiterpenoids (14%) as compared to flower
      oil (44.6% and 1.2%, respectively). However, the flower oil was predominant in
      oxygenated monoterpenes (43.5%). Although both leaf and flower oils showed
      highest cytotoxicity on A549 cells (61.4%+/-5.0 and 66.7%+/-2.2, respectively),
      only 100 MUg/mL flower oil was significantly active against C-6 cells (69.1%+/
      3.1). Interestingly, no toxicity was recorded on normal cells. CONCLUSION: Higher
      concentration of 1,8-cineole and/or synergistic effect of the overall composition
      were probably responsible for the efficacy of flower and leaf oils against the
      tested cells. These oils may form potential source of natural anti-cancer
      compounds and play important role in human health.

PMID- 26308917
TI  - Effect of benzoic acid on the removal of 1,2-dichloroethane by a siderite
      catalyzed hydrogen peroxide and persulfate system.
AB  - Benzoic acid can affect the iron-oxide mineral dissolution and react with
      hydroxyl radical. This study investigated its effect on 1,2-dichloroethane
      removal process by siderite-catalyzed hydrogen peroxide and persulfate. The
      variation of benzoic acid concentrations can affect pH value and soluble iron
      concentrations; when benzoic acid varied from 0 to 0.5 mmol/L, pH increased while
      Fe(2+) and Fe(3+) concentrations decreased, resulting in 1,2-dichloroethane
      removal efficiency which decreased from 91.2 to 5.0%. However, when benzoic acid
      varied from 0.5 to 10 mmol/L, pH decreased while Fe(2+) and Fe(3+) concentrations
      increased, resulting in 1,2-dichloroethane removal efficiency which increased
      from 5.0 to 83.4%.

PMID- 26308918
TI  - Recent evolution of the physical-chemical characteristics of a Site of National
      Interest-the Mar Piccolo of Taranto (Ionian Sea)-and changes over the last 20
      years.
AB  - The Mar Piccolo of Taranto, classified as a 'Site of National Interest' (SIN), is
      a semi-enclosed basin divided into two inlets with lagoon features and sea
      influences, seriously affected by anthropic activities. In the framework of the
      RITMARE project, a study has been carried out to evaluate the functionality of
      this ecosystem. As part of this work, measurements of the water abiotic
      parameters were performed in order to assess the physical-chemical features of
      this area after the activation, in the last decade, of treatment plants for
      various urban and industrial dumping. Seawater intrusions and continental inputs,
      as well as several submarine freshwater springs, clearly affect physical-chemical
      characteristics of the water column in the two inlets. This finding suggests that
      small-scale patterns in water circulation have the potential to influence the
      chemical properties of the seawater. The comparison with a 20-year dataset
      reveals a drastic decrease in nutrient concentrations after the year 2000,
      validating the functionality of the treatment plants. The reduction of nutrient
      inputs into the basin (up to -90 % in the first inlet characterized by lower
      hydraulic residence time) has changed the biogeochemical characteristics of the
      Mar Piccolo from being relatively eutrophic to moderately oligotrophic. 

PMID- 26308919
TI  - Variation of physicochemical properties of drinking water treatment residuals and
      Phoslock((r)) induced by fulvic acid adsorption: Implication for lake
      restoration.
AB  - The use of phosphorus (P) inactivating agents to reduce internal P loading from
      sediment for lake restoration has attracted increasing attention. Reasonably, the
      physicochemical properties of P inactivating agents may vary with the
      interference of various environmental factors, leading to the change of control
      effectiveness and risks. In this study, the effect of fulvic acid (FA) adsorption
      on the properties of two agents, drinking water treatment residuals (DWTRs) and
      Phoslock(r), was investigated. The results showed that after adsorption, there
      was little change for the main structures of DWTRs and Phoslock(r), but the
      thermostability of Phoslock(r), as well as the particle size and settleability of
      the two agents decreased. The specific surface area and pore volume of DWTRs also
      decreased, while those of Phoslock(r) increased. Further analysis indicated that
      aluminum and iron in DWTRs were stable during FA adsorption, but a substantial
      increase of lanthanum release from Phoslock(r) was observed, in particular at
      first (P < 0.01). Moreover, the P immobilization capability of DWTRs had little
      change after FA adsorption, while the capability of Phoslock(r) after FA
      adsorption decreased in solutions (P < 0.001) and sediments (P < 0.1);
      interestingly, from the view of engineering application, the performance of
      Phoslock(r) was not substantially affected. Overall, each P inactivating agent
      had its own particular responses of the physicochemical properties to environment
      factors, and detailed investigations on the applicability of each agent were
      essential before practical application. 

PMID- 26308920
TI  - Analytical, toxicological and kinetic investigation of decomposition of the drug
      diclofenac in waters and wastes using gamma radiation.
AB  - The radiolytic decomposition of the drug diclofenac (DCF), and in limited extent,
      also two other widely used drugs, ibuprofen and carbamazepine, was examined using
      liquid chromatography (LC) methods. The efficiency of DCF decomposition was
      examined in function of the absorbed dose of gamma radiation, and also in the
      presence of selected scavengers of radicals, which are commonly present in
      natural waters and wastes. Three different tests were employed for the monitoring
      of toxicity changes in the irradiated DCF solutions. The LC/mass spectrometry
      (MS) was used for the determination of products of DCF radiolysis. Using pulse
      radiolysis method with the spectrophotometric detection, the rate constant values
      were determined for reactions of DCF with the main products of water radiolysis:
      hydroxyl radicals (1.24 +/- 0.02) * 10(10) M(-1) s(-1) and hydrated electrons
      (3.1 +/- 0.2) * 10(9) M(-1) s(-1). Their values indicate that both oxidative and
      reductive processes in radiolytic decomposition of DCF can take place in
      irradiated diluted aqueous solutions of DCF. The possibility of decomposition of
      all examined analytes was investigated in samples of river water and hospital
      waste. Compared to the previous studies, the conducted measurements in real
      samples were carried out at the concentration levels, which are close to those
      reported earlier in environmental samples. Graphical abstract ?.

PMID- 26308921
TI  - Valorisation of smooth hound (Mustelus mustelus) waste biomass through recovery
      of functional, antioxidative and antihypertensive bioactive peptides.
AB  - Concerns over the environmental and waste disposal problems created by the large
      amounts of by-products generated from fish processing industries are increasing
      worldwide. The bioconversion of those marine waste by-products through the
      enzymatic hydrolysis of their protein content offers the possibility for the
      development of bioactive peptides for use in various biotechnological
      applications. The present study aimed to investigate and evaluate the biological
      and functional properties of smooth hound (Mustelus mustelus) protein
      hydrolysates (SHPHs) obtained by treatment with intestinal and gastric enzyme
      preparations from M. mustelus viscera and porcine pancreatin. The results
      revealed that the SHPHs exhibited different degrees of hydrolysis and antioxidant
      activity. The hydrolysate produced by the intestinal crude extract presented the
      highest rate of antioxidative activity, showing an IC50 value of 1.47 +/- 0.07
      mg/mL in 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assays. The alkaline
      protease extract from the intestine of M. mustelus produced hydrolysate with the
      highest angiotensin I-converting enzyme (ACE) inhibitory activity (82 +/- 1.52%
      at 2 mg/mL). All the protein hydrolysates showed excellent solubility and
      interfacial properties that were governed by pH. The major amino acids detected
      in SHPHs were glutamic acid/glutamine, aspartic acid/asparagine, histidine and
      arginine, followed by methionine, phenylalanine, serine, valine and leucine.
      Overall, the results indicated that smooth hound by-products can be used to
      generate high value-added products, thus offering a valuable source of bioactive
      peptides for application in wide range of biotechnological and functional food
      applications.

PMID- 26308922
TI  - Removal efficiency of particulate matters at different underlying surfaces in
      Beijing.
AB  - Particulate matter (PM) pollution has been increasingly becoming serious in
      Beijing and has drawn the attention of the local government and general public.
      This study was conducted during early spring of 2013 and 2014 to monitor the
      concentration of PM at three different land surfaces (bare land, urban forest,
      and lake) in the Olympic Park in Beijing and to analyze its effect on the
      concentration of meteorological factors and the dry deposition onto different
      land cover types. The results showed that diurnal variation of PM concentrations
      at the three different land surfaces had no significant regulations, and sharp
      short-term increases in PM10 (particulate matter having an aerodynamic diameter
      <10 MUm) occurred occasionally. The concentrations also differed from one land
      cover type to another at the same time, but the regulation was insignificant. The
      most important meteorological factor influencing the PM concentration is relative
      humidity; it is positively correlated with the PM concentration. While in the
      forests, the wind speed and irradiance also influenced the PM concentration by
      affecting the capture capacity of trees and dry deposition velocity. Other
      factors were not correlated with or influenced by the PM concentration. In
      addition, the hourly dry deposition in unit area (MUg/m(2)) onto the three types
      of land surfaces and the removal efficiency based on the ratio of dry deposition
      and PM concentration were calculated. The results showed that the forest has the
      best removal capacity for both PM2.5 (particulate matter having an aerodynamic
      diameter <2.5 MUm) and PM10 because of the faster deposition velocity and
      relatively low resuspension rate. The lake's PM10 removal efficiency is higher
      than that of the bare land because of the relatively higher PM resuspension rates
      on the bare land. However, the PM2.5 removal efficiency is lower than that of the
      bare land because of the significantly lower dry deposition velocity. 

PMID- 26308923
TI  - Spatial and temporal trends of ozone distribution in the Jizerske hory Mountains
      of the Czech Republic.
AB  - We present results of the 5-year monitoring of ambient O3 concentrations in a
      Central European medium altitude mountain forested area. O3 levels were measured
      at 11 sites between 714 and 1000 m a.s.l. in 2006-2010 vegetation seasons using
      Ogawa diffusive samplers. Our results reveal that O3 exposure in the Jizerske
      hory Mts. was relatively high and comparable with polluted sites in Southern
      Europe and in higher altitudes. O3 concentrations differed significantly between
      individual sites and in individual years. O3 concentrations showed clear
      dependence on altitude at sites with similar aspect. Its gradient for the entire
      5-year period under review equaled 3.5 ppb/100 m of altitude, ranging between
      nearly 5 ppb/100 m of altitude in 2006 and nearly 3 ppb/100 m of altitude in
      2010. O3 concentrations at the site with northern aspect were consistently
      significantly lower than at the site at similar altitude with southern aspect. O3
      concentrations measured at the forest edge were consistently lower than those
      measured at the same site but at the forest clearing. It is evident that the
      macro-setting of the O3 monitoring site is crucial for obtaining reliable results
      with high representativeness for the area.

PMID- 26308924
TI  - Using dual isotopes to identify sources and transformations of nitrogen in water
      catchments with different land uses, Loess Plateau of China.
AB  - Nitrogen pollution in rivers is a research hotspot in the field of
      biogeochemistry. However, the types and sources of pollution have historically
      been poorly understood in the water catchments of the Loess Plateau in China. In
      this study, we have chosen the main waterway and four lesser branches of the
      Jinghe River that vary by land use. We investigated the concentrations and
      isotopic signatures of nitrogen in river water. Our results revealed that nitrate
      was the dominant nitrogen type in river catchments of the Loess Plateau. The
      delta(15)N and delta(18)O values showed that NO3 (-) ions in the studied river
      samples were derived from precipitation, manure, sewage, soil organic nitrogen,
      and synthetic NO3 (-) fertilizer. The delta(18)O-NO3 (-) values during July 2012
      (mean +/- SD = +18.1 +/- 1.50/00) were higher than those during the September
      2013 (mean +/- SD = +7.8 +/- 3.70/00), which indicated that mixing with
      atmospheric NO3 (-) resulted in the high delta(18)O values during July 2012. It
      appears that no intense nitrification and denitrification occurred in all five
      rivers according to the isotopic and chemical data. A Bayesian model was used to
      determine the contributions of four NO3 (-) sources to all five rivers. Results
      showed that source contributions differ significantly between July and September,
      and the four potential NO3 (-) sources also showed high variability between the
      different land use areas.

PMID- 26308925
TI  - Influence of different formulations on chlorpyrifos behavior and risk assessment
      in bamboo forest of China.
AB  - The effects of two formulations (emulsifiable concentrate (EC) and granule (G))
      on the distribution, degradation, sorption, and residue risk of chlorpyrifos
      (CHP) were investigated in two producing areas of bamboo shoot. The results
      showed that CHP was mainly distributed in the topsoil (0-5 cm, P < 0.05), with
      the proportion of CHP in the total quantity ranging from 76.0 to 100.0 % (G) and
      12.0 to 98.1 % (EC), respectively. The degradation of CHP-EC in soils (half-life
      27.7-36.4 days) was faster than that of CHP-G in soils (half life above 120-150
      days). The main metabolite of CHP, 3,5,6-trichloro-2-pyridinol (TCP), was found
      in soil samples. CHP showed good sorption ability in the two tested soils, with
      the sorption coefficient (KF) of 43.76 and 94.43 mg/kg. The terminal residues of
      CHP in bamboo shoots were in the range of 15.2-75.6 (G) and 10.4-35.7 MUg/kg
      (EC), respectively. The soil type had a notable effect on the CHP behaviors in
      soil (P < 0.05, especially for CHP-G), but it did not affect the metabolite of
      CHP. Although some positive bamboo shoot samples (CHP residue exceeding maximum
      residue limits) were found, the hazard quotients did not exceed 7 %, which meant
      there was a negligible risk associated with the exposure to CHP via the
      consumption of bamboo shoots.

PMID- 26308926
TI  - Different senescent HDPE pipe-risk: brief field investigation from source water
      to tap water in China (Changsha City).
AB  - Semi-volatile organic compounds (SVOCs) derived from plastic pipes widely used in
      water distribution definitely influence our daily drinking water quality. There
      are still few scientific or integrated studies on the release and degradation of
      the migrating chemicals in pipelines. This investigation was carried out at field
      sites along a pipeline in Changsha, China. Two chemicals, 2, 4-tert-buthylphenol
      and 1, 3-diphenylguanidine, were found to be migrating from high density
      polyethylene (HDPE) pipe material. New pipes released more of these two compounds
      than older pipes, and microorganisms living in older pipes tended to degrade them
      faster, indicating that the aged pipes were safer for water transmission.
      Microorganism degradation in water plays a dominant role in the control of these
      substances. To minimize the potential harm to human, a more detailed study
      incorporating assessment of their risk should be carried out, along with seeking
      safer drinking pipes. 

PMID- 26308927
TI  - Predicting biofilm thickness and biofilm viability based on the concentration of
      carbon-nitrogen-phosphorus by support vector regression.
AB  - Current tools to predict biofilm thickness and viability in spatial distribution
      are poor, especially those based on chemical oxygen demand (COD), total nitrogen
      (TN), and total phosphate (TP) due to their limited data and complex
      calculations. Here, support vector regression (SVR) was used to predict biofilm
      thickness and viability in a reactor filled with carriers of crushed stone
      globular aggregates. Analyses combined confocal laser scanning microscopy and
      flow cytometry with Kriging interpolation revealed that biofilm thickness varied
      from 22 to 31 MUm, and biofilm viability decreased from 80 to 30% in the flow
      direction of the reactor. The biofilm thickness at the bottom was thicker than
      that in the upper layer, but biofilm viability contrasted with biofilm thickness
      in the vertical distribution. The values of biofilm thickness and viability were
      predicted at a layer 35 cm from the bottom of the reactor with mean squared error
      values of 0.014 and 0.011, respectively. Correlation coefficients were 0.996 and
      0.997 between carbon-nitrogen-phosphorus (C-N-P) removal with biofilm thickness
      and viability in spatial distribution, respectively. This study provided an
      important mathematical method to predict biofilm thickness and viability in
      spatial distribution based on the concentration of C-N-P.

PMID- 26308928
TI  - Monitoring Spawning Activity in a Southern California Marine Protected Area Using
      Molecular Identification of Fish Eggs.
AB  - In order to protect the diverse ecosystems of coastal California, a series of
      marine protected areas (MPAs) have been established. The ability of these MPAs to
      preserve and potentially enhance marine resources can only be assessed if these
      habitats are monitored through time. This study establishes a baseline for
      monitoring the spawning activity of fish in the MPAs adjacent to Scripps
      Institution of Oceanography (La Jolla, CA, USA) by sampling fish eggs from the
      plankton. Using vertical plankton net tows, 266 collections were made from the
      Scripps Pier between 23 August 2012 and 28 August 2014; a total of 21,269 eggs
      were obtained. Eggs were identified using DNA barcoding: the COI or 16S rRNA gene
      was amplified from individual eggs and sequenced. All eggs that were successfully
      sequenced could be identified from a database of molecular barcodes of California
      fish species, resulting in species-level identification of 13,249 eggs.
      Additionally, a surface transport model of coastal circulation driven by current
      maps from high frequency radar was used to construct probability maps that
      estimate spawning locations that gave rise to the collected eggs. These maps
      indicated that currents usually come from the north but water parcels tend to be
      retained within the MPA; eggs sampled at the Scripps Pier have a high probability
      of having been spawned within the MPA. The surface transport model also suggests
      that although larvae have a high probability of being retained within the MPA,
      there is also significant spillover into nearby areas outside the MPA. This study
      provides an important baseline for addressing the extent to which spawning
      patterns of coastal California species may be affected by future changes in the
      ocean environment. 

PMID- 26308929
TI  - Ni-Supported Pd Nanoparticles with Ca Promoter: A New Catalyst for Low
      Temperature Ammonia Cracking.
AB  - In this paper we report a new nanometallic, self-activating catalyst, namely, Ni
      supported Pd nanoparticles (PdNPs/Ni) for low temperature ammonia cracking, which
      was prepared using a novel approach involving the transfer of nanoparticles from
      the intermediate carrier, i.e. nano-spherical SiO2, to the target carrier
      technical grade Ni (t-Ni) or high purity Ni (p-Ni) grains. The method that was
      developed allows a uniform nanoparticle size distribution (4,4+/-0.8 nm) to be
      obtained. Unexpectedly, the t-Ni-supported Pd NPs, which seemed to have a surface
      Ca impurity, appeared to be more active than the Ca-free (p-Ni) system. A
      comparison of the novel PdNPs/Ni catalyst with these reported in the literature
      clearly indicates the much better hydrogen productivity of the new system, which
      seems to be a highly efficient, flexible and durable catalyst for gas-phase
      heterogeneous ammonia cracking in which the TOF reaches a value of 2615
      mmolH2/gPd min (10,570 molNH3/molPd(NP) h) at 600 degrees C under a flow of 12
      dm3/h (t-Ni). 

PMID- 26308931
TI  - Sub-Tenon's anaesthesia versus topical anaesthesia for cataract surgery.
AB  - BACKGROUND: Local anaesthesia for cataract surgery can be provided by sub-Tenon's
      or topical anaesthesia. Both techniques offer possible advantages. This review,
      which originally was published in 2007 and was updated in 2014, was undertaken to
      compare these two anaesthetic techniques. OBJECTIVES: Our objectives were to
      compare the effectiveness of topical anaesthesia (with or without intracameral
      local anaesthetic) versus sub-Tenon's anaesthesia in providing pain relief during
      cataract surgery. We reviewed pain during administration of anaesthesia,
      postoperative pain, surgical satisfaction with operating conditions and patient
      satisfaction with pain relief provided, and we looked at associated
      complications. SEARCH METHODS: We searched the Cochrane Central Register of
      Controlled Trials, MEDLINE and EMBASE (last search in November 2014) and the
      reference lists of published articles. We looked for conferences abstracts and
      trials in progress and placed no constraints on language or publication status.
      SELECTION CRITERIA: We included all randomized studies that compared sub-Tenon's
      anaesthesia versus topical anaesthesia for cataract surgery. DATA COLLECTION AND
      ANALYSIS: We assessed trial quality and extracted data in the format allowing
      maximal data inclusion. MAIN RESULTS: We included eight studies in this updated
      review but could retain in the analysis only seven studies on 742 operated eyes
      of 617 participants. Two cross-over trials included 125 participants, and five
      parallel trials included 492 participants. These studies were published between
      1997 and 2005. The mean age of participants varied from 71.5 years to 83.5 years.
      The female proportion of participants varied from 54% to 76%. Compared with sub
      Tenon's anaesthesia, topical anaesthesia (with or without intracameral injection)
      for cataract surgery increases intraoperative pain but decreases postoperative
      pain at 24 hours. The amplitude of the effect (equivalent to 1.1 on a score from
      0 to 10 for intraoperative pain, and to 0.2 on the same scale for postoperative
      pain at 24 hours), although statistically significant, was probably too small to
      be of clinical relevance. The quality of the evidence was rated as high for
      intraoperative pain and moderate for pain at 24 hours. We did find differences in
      pain during administration of local anaesthetic (low level of evidence), and
      indications that surgeon satisfaction (low level of evidence) and participant
      satisfaction (moderate level of evidence) were less with topical anaesthesia.
      There was not enough evidence to say that one technique would result in a higher
      or lower incidence of intraoperative complications compared with the other.
      AUTHORS' CONCLUSIONS: Both topical anaesthesia and sub-Tenon's anaesthesia are
      accepted and safe methods of providing anaesthesia for cataract surgery. An
      acceptable degree of intraoperative discomfort has to be expected with either of
      these techniques. Randomized controlled trials on the effects of various
      strategies to prevent intraoperative pain during cataract surgery could prove
      useful.

PMID- 26308930
TI  - Altered Exosomal RNA Profiles in Bronchoalveolar Lavage from Lung Transplants
      with Acute Rejection.
AB  - RATIONALE: The mechanism by which acute allograft rejection leads to chronic
      rejection remains poorly understood despite its common occurrence. Exosomes,
      membrane vesicles released from cells within the lung allograft, contain a
      diverse array of biomolecules that closely reflect the biologic state of the cell
      and tissue from which they are released. Exosome transcriptomes may provide a
      better understanding of the rejection process. Furthermore, biomarkers
      originating from this transcriptome could provide timely and sensitive detection
      of acute cellular rejection (AR), reducing the incidence of severe AR and chronic
      lung allograft dysfunction and improving outcomes. OBJECTIVES: To provide an in
      depth analysis of the bronchoalveolar lavage fluid exosomal shuttle RNA
      population after lung transplantation and evaluate for differential expression
      between acute AR and quiescence. METHODS: Serial bronchoalveolar lavage specimens
      were ultracentrifuged to obtain the exosomal pellet for RNA extraction, on which
      RNA-Seq was performed. MEASUREMENTS AND MAIN RESULTS: AR demonstrates an intense
      inflammatory environment, skewed toward both innate and adaptive immune
      responses. Novel, potential upstream regulators identified offer potential
      therapeutic targets. CONCLUSIONS: Our findings validate bronchoalveolar lavage
      fluid exosomal shuttle RNA as a source for understanding the pathophysiology of
      AR and for biomarker discovery in lung transplantation.

PMID- 26308932
TI  - Targeting Highly Structured RNA by Cooperative Action of siRNAs and Helper
      Antisense Oligomers in Living Cells.
AB  - RNA target accessibility is one of the most important factors limiting the
      efficiency of RNA interference-mediated RNA degradation. However, targeting RNA
      viruses in their poorly accessible, highly structured regions can be advantageous
      because these regions are often conserved in sequence and thus less prone to
      viral escape. We developed an experimental strategy to attack highly structured
      RNA by means of pairs of specifically designed small interfering RNAs and helper
      antisense oligonucleotides using the 5' untranslated region (5'UTR) of
      coxsackievirus B3 as a model target. In the first step, sites accessible to
      hybridization of complementary oligonucleotides were identified using two mapping
      methods with random libraries of short DNA oligomers. Subsequently, the
      accessibility of the mapped regions for hybridization of longer DNA 16-mers was
      confirmed by an RNase H assay. Using criteria for the design of efficient small
      interfering RNAs (siRNA) and a secondary structure model of the viral 5'UTR,
      several DNA 19-mers were designed against partly double-stranded RNA regions.
      Target sites for DNA 19-mers were located opposite the sites which had been
      confirmed as accessible for hybridization. Three pairs of DNA 19-mers and the
      helper 2'-O-methyl-16-mers were able to effectively induce RNase H cleavage in
      vitro. For cellular assays, the DNA 19-mers were replaced by siRNAs, and the
      corresponding three pairs of siRNA-helper oligomer tools were found to target
      5'UTR efficiently in a reporter construct in HeLa cells. Addition of the helper
      oligomer improved silencing capacity of the respective siRNA. We assume that the
      described procedure will generally be useful for designing of nucleic acid-based
      tools to silence highly structured RNA targets. 

PMID- 26308933
TI  - Palladium(II) complexes with chelating N-phosphanyl acyclic diaminocarbenes:
      synthesis, characterization and catalytic performance in Suzuki couplings.
AB  - Complexes of palladium(II) with newly disclosed, N-phosphanyl acyclic
      diaminocarbene ligands are synthesized for the first time and structurally
      characterized. The ligands coordinate palladium(II) in a chelating fashion,
      yielding remarkably stable complexes which can be stored without special
      precautions in the solid state. Related palladium(II) complexes with an
      isomerized chelating ligand, formed upon 1,2-migration of the phosphanyl group
      from the nitrogen to the adjacent carbon atom, have also been isolated in some
      instances and structurally characterized. The complexes efficiently act as
      precatalysts for Suzuki coupling reactions of aryl chlorides, where their
      productivity compares favourably with that of related palladium complexes with
      acyclic diaminocarbene ligands. In addition, the complexes show a distinct
      tendency to form as the byproduct the reductive homocoupling product of aryl
      chloride. This observation, together with ad hoc performed control tests,
      suggests that Pd colloids are involved in the formation of catalytically
      competent species.

PMID- 26308935
TI  - Cell-sized condensed collagen microparticles for preparing microengineered
      composite spheroids of primary hepatocytes.
AB  - The reconstitution of extracellular matrix (ECM) components in three-dimensional
      (3D) cell culture environments with microscale precision is a challenging issue.
      ECM microparticles would potentially be useful as solid particulate scaffolds
      that can be incorporated into 3D cellular constructs, but technologies for
      transforming ECM proteins into cell-sized stable particles are currently lacking.
      Here, we describe new processes to produce highly condensed collagen
      microparticles by means of droplet microfluidics or membrane emulsification.
      Droplets of an aqueous solution of type I collagen were formed in a continuous
      phase of polar organic solvent followed by rapid dissolution of water molecules
      into the continuous phase because the droplets were in a non-equilibrium state.
      We obtained highly unique, disc-shaped condensed collagen microparticles with a
      final collagen concentration above 10% and examined factors affecting particle
      size and morphology. After testing the cell-adhesion properties on the collagen
      microparticles, composite multicellular spheroids comprising the particles and
      primary rat hepatocytes were formed using microfabricated hydrogel chambers. We
      found that the ratio of the cells and particles is critical in terms of
      improvement of hepatic functions in the composite spheroids. The presented
      methodology for incorporating particulate-form ECM components in multicellular
      spheroids would be advantageous because of the biochemical similarity with the
      microenvironments in vivo. 

PMID- 26308936
TI  - Overexpression of Both ERG11 and ABC2 Genes Might Be Responsible for Itraconazole
      Resistance in Clinical Isolates of Candida krusei.
AB  - OBJECTIVE: To study the main molecular mechanisms responsible for itraconazole
      resistance in clinical isolates of Candida krusei. METHODS: The 14alpha
      demethylases encoded by ERG11 gene in the 16 C.krusei clinical isolates were
      amplified by polymerase chain reaction (PCR), and their nucleotide sequences were
      determined to detect point mutations. Meanwhile, ERG11 and efflux transporters
      (ABC1 and ABC2) genes were determined by quantitative real-time reverse
      transcription polymerase chain reaction (qRT-PCR) for their expression in
      itraconazole-resistant (R), itraconazole-susceptible dose dependent (SDD) and
      itraconazole-susceptible (S) C.krusei at the mRNA level. RESULTS: We found 7
      point mutations in ERG11 gene of all the C.krusei clinical isolates, including 6
      synonymous mutations and 1 missense mutation (C44T). However, the missense
      mutation was found in the three groups. The mRNA levels of ERG11 gene in
      itraconazole-resistant isolates showed higher expression compared with
      itraconazole-susceptible dose dependent and itraconazole-susceptible ones (P =
      0.015 and P = 0.002 respectively). ABC2 gene mRNA levels in itraconazole
      resistant group was significantly higher than the other two groups, and the
      levels of their expression in the isolates appeared to increase with the decrease
      of susceptibility to itraconazole (P = 0.007 in SDD compared with S, P = 0.016 in
      SDD with R, and P<0.001 in S with R respectively). While ABC1 gene presented
      lower expression in itraconazole resistant strains. However, the mRNA levels of
      ERG11, ABC1 and ABC2 in a C.krusei (CK10) resistant to both itraconazole and
      voriconazole were expressed highest in all the itraconazole-resistant isolates.
      CONCLUSIONS: There are ERG11 gene polymorphisms in clinical isolates of C.krusei.
      ERG11 gene mutations may not be involved in the development of itraconazole
      resistance in C.krusei. ERG11 and ABC2 overexpression might be responsible for
      the acquired itraconazole resistance of these clinical isolates.

PMID- 26308938
TI  - Commentary on "Effects of Group, Individual and Home Exercise in Persons With
      Parkinson's Disease: A Randomized Clinical Trial".

PMID- 26308937
TI  - Effects of Group, Individual, and Home Exercise in Persons With Parkinson
      Disease: A Randomized Clinical Trial.
AB  - BACKGROUND AND PURPOSE: Comparative studies of exercise interventions for people
      with Parkinson disease (PD) rarely considered how one should deliver the
      intervention. The objective of this study was to compare the success of exercise
      when administered by (1) home exercise program, (2) individualized physical
      therapy, or (3) a group class. We examined if common comorbidities associated
      with PD impacted success of each intervention. METHODS: Fifty-eight people (age =
      63.9 +/- 8 years) with PD participated. People were randomized into (1) home
      exercise program, (2) individual physical therapy, or (3) group class
      intervention. All arms were standardized and based on the Agility Boot Camp
      exercise program for PD, 3 times per week for 4 weeks. The primary outcome
      measure was the 7-item Physical Performance Test. Other measures of balance,
      gait, mobility, quality of life, balance confidence, depressions, apathy, self
      efficacy and UPDRS-Motor, and activity of daily living scores were included.
      RESULTS: Only the individual group significantly improved in the Physical
      Performance Test. The individual exercise showed the most improvements in
      functional and balance measures, whereas the group class showed the most
      improvements in gait. The home exercise program improved the least across all
      outcomes. Several factors effected success, particularly for the home group.
      DISCUSSION AND CONCLUSIONS: An unsupervised, home exercise program is the least
      effective way to deliver exercise to people with PD, and individual and group
      exercises have differing benefits. Furthermore, people with PD who also have
      other comorbidities did better in a program directly supervised by a physical
      therapist.Video Abstract available for additional insights from the authors (see
      Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A112).

PMID- 26308939
TI  - Effectiveness of Exercise Programs for Management of Shoulder Pain in Manual
      Wheelchair Users With Spinal Cord Injury.
AB  - BACKGROUND AND PURPOSE: Shoulder pain is prevalent in manual wheelchair users
      (MWUs) with spinal cord injury (SCI). Therapeutic exercise has been demonstrated
      to be an effective, conservative approach to treating shoulder pain in able
      bodied individuals. We sought to evaluate literature on the effectiveness of
      exercise programs on the reduction of shoulder pain in MWUs with SCI. METHODS: We
      searched the literature, using search terms related to SCI, manual wheelchairs,
      and shoulder pain. Eligibility criteria included prospective study design,
      exercise intervention for MWUs with shoulder pain, and use of the Wheelchair
      User's Shoulder Pain Index as an outcome measure. We followed the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and
      assessed study quality. RESULTS: Three randomized control trials and 4 cohort
      studies met inclusion criteria. Two studies were rated as good quality and 5 as
      fair quality. Three interventions were evaluated in the included studies: arm
      ergometry, resistive strengthening with or without electromyographic biofeedback,
      and stretching that targeted the muscles of the shoulder girdle. Across the 7
      studies, the exercise intervention was associated with reduction in shoulder pain
      that exceeded the estimated minimal detectable change of 5.10 points for the
      Wheelchair Users' Shoulder Pain Index. DISCUSSION AND CONCLUSION: Exercise is a
      feasible, conservative, therapeutic intervention for the treatment of shoulder
      pain among MWUs. Additional studies are needed to differentiate techniques for
      the reduction of shoulder pain, to determine the most effective duration of
      intervention, and to estimate the magnitude of effect associated with therapeutic
      exercise for shoulder pain among MWUs.Video Abstract available for more insights
      from the authors (see Supplemental Digital Content 1,
      http://links.lww.com/JNPT/A116).

PMID- 26308940
TI  - Incremental value of 99mTc-MDP hybrid SPECT/CT over planar scintigraphy and SPECT
      in avascular necrosis of the femoral head.
AB  - OBJECTIVE: The aim of the study was to evaluate the incremental value of
      technetium-99m-methylene diphosphonate (99mTc-MDP) single-photon emission
      tomography/computed tomography (SPECT/CT) over planar bone scintigraphy (BS) and
      SPECT in the diagnosis of avascular necrosis (AVN) of the femoral head. MATERIALS
      AND METHODS: The data of 44 patients (mean age 36 +/- 16 years, 34 male and 10
      female) who underwent 99mTc-MDP BS along with regional SPECT/CT for suspected
      femoral head AVN were retrospectively evaluated. Planar BS, SPECT and SPECT/CT
      images were evaluated by two nuclear medicine physicians in consensus. On the
      basis of diagnostic confidence, a score of 1-5 was given, with 1 being definitely
      AVN, 2 being probably AVN, 3 being equivocal, 4 being probably normal and 5 being
      definitely normal. Receiver operating characteristic analysis was performed and
      the area under the curve was calculated. For calculation of sensitivity,
      specificity and predictive values for planar, an interpretive score of less than
      or equal to 2 was taken as AVN and a score of 3 or more was taken as no AVN.
      Clinical and imaging follow-up and histopathological results were taken as the
      reference standard. RESULTS: Among 44 patients with 64 affected femoral heads,
      there were 48 true-positive, 13 true-negative, two false-positive and one false
      negative lesion on SPECT/CT. The diagnostic accuracy of planar BS, SPECT and
      SPECT/CT was 67, 78 and 95%, respectively. Planar BS was found to have the lowest
      sensitivity (75%) and specificity (40%), whereas SPECT/CT had the highest
      sensitivity (98%) and specificity (87%). The area under the curve was highest for
      SPECT/CT (0.919), followed by SPECT (0.76) and planar BS (0.567). SPECT/CT was
      superior to both SPECT (P = 0.02) and planar BS (P < 0.001), whereas SPECT was
      superior to planar BS (P = 0.03). CONCLUSION: SPECT/CT is superior to planar BS
      and SPECT alone for the diagnosis of AVN of the femoral head.

PMID- 26308941
TI  - Tetrahydrohyperforin Inhibits the Proteolytic Processing of Amyloid Precursor
      Protein and Enhances Its Degradation by Atg5-Dependent Autophagy.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the
      accumulation of amyloid-beta (Abeta) peptide. We have previously shown that the
      compound tetrahydrohyperforin (IDN5706) prevents accumulation of Abeta species in
      an in vivo model of AD, however the mechanism that explains this reduction is not
      well understood. We show herein that IDN5706 decreases the levels of ER
      degradation enhancer, mannosidase alpha-like 1 (EDEM1), a key chaperone related
      to endoplasmic-reticulum-associated degradation (ERAD). Moreover, we observed
      that low levels of EDEM1 correlated with a strong activation of autophagy,
      suggesting a crosstalk between these two pathways. We observed that IDN5706
      perturbs the glycosylation and proteolytic processing of the amyloid precursor
      protein (APP), resulting in the accumulation of immature APP (iAPP) in the
      endoplasmic reticulum. To investigate the contribution of autophagy, we tested
      the effect of IDN5706 in Atg5-depleted cells. We found that depletion of Atg5
      enhanced the accumulation of iAPP in response to IDN5706 by slowing down its
      degradation. Our findings reveal that IDN5706 promotes degradation of iAPP via
      the activation of Atg5-dependent autophagy, shedding light on the mechanism that
      may contribute to the reduction of Abeta production in vivo. 

PMID- 26308943
TI  - Stereoselective synthesis of octahydrocyclohepta[c]pyran-6(1H)-one scaffolds
      through a Prins/alkynylation/hydration sequence.
AB  - Aldehydes undergo a smooth coupling with (E/Z)-non-3-en-8-yn-1-ol in the presence
      of 10 mol% of CuX and BF3.OEt2 under mild conditions to produce a novel class of
      octahydrocyclohepta[c]pyran-6(1H)-one derivatives in good yields with excellent
      diastereoselectivity through a sequential Prins/alkynylation/hydration. This is
      the first report on the termination of Prins cyclization with a tethered alkyne. 

PMID- 26308942
TI  - FFCD-1004 Clinical Trial: Impact of Cytidine Deaminase Activity on Clinical
      Outcome in Gemcitabine-Monotherapy Treated Patients.
AB  - PURPOSE: Because cytidine deaminase (CDA) is the key enzyme in gemcitabine
      metabolism, numerous studies have attempted to investigate impact of CDA status
      (i.e. genotype or phenotype) on clinical outcome. To date, data are still
      controversial because none of these studies has fully investigated genotype
      phenotype CDA status, pharmacokinetics and clinical outcome relationships in
      gemcitabine-treated patients. Besides, most patients were treated with
      gemcitabine associated with other drugs, thus adding a confounding factor. We
      performed a multicenter prospective clinical trial in gemcitabine-treated
      patients which aimed at investigating the link between CDA deficiency on the
      occurrence of severe toxicities and on pharmacokinetics, and studying CDA
      genotype-phenotype relationships. EXPERIMENTAL DESIGN: One hundred twenty
      patients with resected pancreatic adenocarcinoma eligible for adjuvant
      gemcitabine monotherapy were enrolled in this study promoted and managed by the
      Federation Francophone de Cancerologie Digestive. Toxicities were graded
      according to National Cancer Institute's Common Terminology Criteria for Adverse
      Events Version 4. They were considered severe for grade >= 3, and early when
      occurring during the first eight weeks of treatment. CDA status was evaluated
      using a double approach: genotyping for 79A>C and functional testing. Therapeutic
      drug monitoring of gemcitabine and its metabolite were performed on the first
      course of gemcitabine. RESULTS: Five patients out of 120 (i.e., 4.6%) were found
      to be CDA deficient (i.e., CDA activity <1.3 U/mg), and only one among them
      experienced early severe hematological toxicity. There was no statistically
      significant difference in CDA activity between patients experiencing
      hematological severe toxicities (28.44%) and patients who tolerated the treatment
      (71.56%). CDA genetic analysis failed in evidencing an impact in terms of
      toxicities or in CDA activity. Regarding pharmacokinetics, a wide inter
      individual variability has been observed in patients. CONCLUSION: This study,
      which included only 4.6% of CDA-deficient patients, failed in identifying CDA
      status as a predictive marker of toxicities with gemcitabine. A lack of
      statistical power because of smoothing effect of CDA variability as compared with
      real life conditions could explain this absence of impact. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01416662.

PMID- 26308944
TI  - Targeting Artificial Tumor Stromal Targets for Molecular Imaging of Tumor
      Vascular Hypoxia.
AB  - Developed and tested for many years, a variety of tumor hypoxia detection methods
      have been inconsistent in their ability to predict treatment outcomes or monitor
      treatment efficacy, limiting their present prognostic capability. These variable
      results might stem from the fact that these approaches are based on inherently
      wide-ranging global tumor oxygenation levels based on uncertain influences of
      necrotic regions present in most solid tumors. Here, we have developed a novel
      non-invasive and specific method for tumor vessel hypoxia detection, as hypoxemia
      (vascular hypoxia) has been implicated as a key driver of malignant progression,
      therapy resistance and metastasis. This method is based on high-frequency
      ultrasound imaging of alpha-pimonidazole targeted-microbubbles to the exogenously
      administered hypoxia marker pimonidazole. The degree of tumor vessel hypoxia was
      assessed in three mouse models of mammary gland carcinoma (4T1, SCK and MMTV-Wnt
      1) and amassed up to 20% of the tumor vasculature. In the 4T1 mammary gland
      carcinoma model, the signal strength of alpha-pimonidazole targeted-microbubbles
      was on average 8-fold fold higher in tumors of pimonidazole-injected mice than in
      non-pimonidazole injected tumor bearing mice or non-targeted microbubbles in
      pimonidazole-injected tumor bearing mice. Overall, this provides proof of
      principle for generating and targeting artificial antigens able to be 'created'
      on-demand under tumor specific microenvironmental conditions, providing
      translational diagnostic, therapeutic and treatment planning potential in cancer
      and other hypoxia-associated diseases or conditions. 

PMID- 26308945
TI  - The Troy Microneedle: A Rapidly Separating, Dissolving Microneedle Formed by
      Cyclic Contact and Drying on the Pillar (CCDP).
AB  - In dissolving microneedle (DMN)-mediated therapy, complete and rapid delivery of
      DMNs is critical for the desired efficacy. Traditional patch-based DMN delivery,
      however, may fail due to incomplete delivery from insufficient skin insertion or
      rapid separation of microneedles due to their strong bond to the backing film.
      Here, we introduce the Troy microneedle, which was created by cyclic contact and
      drying on the pillar (CCDP), and which enabled simultaneous complete and rapid
      delivery of DMN. This CCDP process could be flexibly repeated to achieve a
      specific desired drug dose in a DMN. We evaluated DMN separation using agarose
      gel, and the Troy microneedle achieved more complete and rapid separation than
      other, more deeply dipped DMN, primarily because of the Troy's minimal junction
      between the DMN and pillar. When Troy microneedles were applied to pig cadaver
      skin, it took only 15 s for over 90% of encapsulated rhodamine B to be delivered,
      compared to 2 h with application of a traditional DMN patch. In vivo skin
      penetration studies demonstrated rapid DMN-separation of Troy microneedles still
      in solid form before dissolution. The Troy microneedle overcomes critical issues
      associated with the low penetration efficiency of flat patch-based DMN and
      provides an innovative route for DMN-mediated therapy, combining patient
      convenience with the desire drug efficacy. 

PMID- 26308946
TI  - Randomized Controlled Trial to Determine the Impact of Probiotic Administration
      on Colonization With Multidrug-Resistant Organisms in Critically Ill Patients.
AB  - This was a randomized controlled pilot study of Lactobacillus rhamnosus GG versus
      standard of care to prevent gastrointestinal multidrug-resistant organism
      colonization in intensive care unit patients. Among 70 subjects, there were no
      significant differences in acquisition or loss of any multidrug-resistant
      organisms (P>.05) and no probiotic-associated adverse events.

PMID- 26308947
TI  - The influence of quarantine on reproductive cycling in wild-caught Baboons (Papio
      anubis).
AB  - Stress impacts nonhuman primate menstrual cycle length but the impact of
      quarantine is unknown. A retrospective analysis was performed on cycle data from
      31 wild-caught baboons during and following quarantine. Cycling initiated in 94
      days (19-181) and length normalized within 4-6 cycles. Quarantine significantly
      impacts menstrual cycle length.

PMID- 26308948
TI  - Mechanical properties and structure-function relationships in articular cartilage
      repaired using IGF-I gene-enhanced chondrocytes.
AB  - Several studies have demonstrated the benefits of IGF-I gene therapy in enhancing
      the histologic and biochemical content of cartilage repaired by chondrocyte
      transplantation. However, there is little to no data on the mechanical
      performance of IGF-I augmented cartilage grafts. This study evaluated the
      compressive properties of full-thickness chondral defects in the equine femur
      repaired with and without IGF-I gene therapy. Animals were randomly assigned to
      one of three study cohorts based on chondrocyte treatment provided in each
      defect: (i) IGF-I gene delivered by recombinant adeno-associated virus (rAAV)-5;
      (ii) AAV-5 delivering GFP as a reporter; (iii) naive cells without virus. In each
      case, the opposite limb was implanted with a fibrin carrier without cells.
      Samples were prepared for confined compression testing to measure the aggregate
      modulus and hydraulic permeability. All treatment groups, regardless of cell
      content or transduction, had mechanical properties inferior to native cartilage.
      Overexpression of IGF-I increased modulus and lowered permeability relative to
      other treatments. Investigation of structure-property relationships revealed that
      Ha and k were linearly correlated with GAG content but logarithmically correlated
      with collagen content. This provides evidence that IGF-I gene therapy can improve
      healing of articular cartilage and can greatly increase the mechanical properties
      of repaired grafts.

PMID- 26308949
TI  - Why the cognitive science of religion cannot rescue 'spiritual care'.
AB  - Peter Kevern believes that the cognitive science of religion (CSR) provides a
      justification for the idea of spiritual care in the health services. In this
      paper, I suggest that he is mistaken on two counts. First, CSR does not entail
      the conclusions Kevern wants to draw. His treatment of it consists largely of
      nonsequiturs. I show this by presenting an account of CSR, and then explaining
      why Kevern's reasons for thinking it rescues 'spirituality' discourse do not
      work. Second, the debate about spirituality-in-health is about classification:
      what shall count as a 'spiritual need' and what shall count as 'spiritual care'.
      It is about the politics of meaning, an exercise in persuasive definition. The
      function of 'spirituality' talk in health care is to change the denotation of
      'spiritual', and attach its indelibly religious connotations to as many health
      related concepts and practices as possible. CSR, however plausible it may be as a
      theory of the origins and pervasiveness of religious belief, is irrelevant to
      this debate. 

PMID- 26308951
TI  - Steric Effects on the Structures, Reactivity, and Coordination Chemistry of
      Tris(2-pyridyl)aluminates.
AB  - Introducing substituents in the 6-position of the 2-pyridyl rings of
      tris(pyridyl)aluminate anions, of the type [EtAl(2-py')3 ](-) (py'=a substituted
      2-pyridyl group), has a large impact on their metal coordination characteristics.
      This is seen most remarkably in the desolvation of the THF solvate [EtAl(6-Me-2
      py)3 Li?THF] to give the monomer [EtAl(6-Me-2-py)3 Li] (1), containing a
      pyramidal, three-coordinate Li(+) cation. Similar monomeric complexes are
      observed for [EtAl(6-CF3 -2-py)3 Li] (2) and [EtAl(6-Br-2-py)3 Li] (3), which
      contain CF3 and Br substituents (R). This steric influence can be exploited in
      the synthesis of a new class of terminal Al-OH complexes, as is seen in the
      controlled hydrolysis of 2 and 3 to give [EtAl(OH)(6-R-2-py)2 ](-) anions, as in
      the dimer [EtAl(OH)(6-Br-2-py)2 Li]2 (5). Attempts to deprotonate the Al-OH group
      of 5 using Et2 Zn led only to the formation of the zincate complex [LiZn(6-Br
      py)3 ]2 (6), while reactions of the 6-Br substituted 3 and the unsubstituted
      complex [EtAl(2-py)3 Li] with MeOH give [EtAl(OMe)(6-Br-2-py)2 Li]2 (7) and
      [EtAl(OMe)(2-py)2 Li]2 (8), respectively, having similar dimeric arrangements to
      5. The combined studies presented provide key synthetic methods for the
      functionalization and elaboration of tris(pyridyl)aluminate ligands.

PMID- 26308950
TI  - Pathway-Based Genome-Wide Association Studies for Plasma Triglycerides in Obese
      Females and Normal-Weight Controls.
AB  - Pathway-based analysis as an alternative approach can provide complementary
      information to single-marker genome-wide association studies (GWASs), which
      always ignore the epistasis and does not have sufficient power to find rare
      variants. In this study, using genotypes from a genome-wide association study
      (GWAS), pathway-based association studies were carried out by a modified Gene Set
      Enrichment Algorithm (GSEA) method (GenGen) for triglyceride in 1028 unrelated
      European-American extremely obese females (BMI>=35kg/m2) and normal-weight
      controls (BMI<25kg/m2), and another pathway association analysis (ICSNPathway)
      was also used to verify the GenGen result in the same data. The GO0009110 pathway
      (vitamin anabolism) was among the strongest associations with triglyceride
      (empirical P<0.001); the result remained significant after FDR correction (P =
      0.022). MMAB, an obesity-related locus, included in this pathway. The ABCG1 and
      BCL6 gene was found in several triglyceride-related pathways (empirical P<0.05),
      which were also replicated by ICSNPathway (empirical P<0.05, FDR<0.05). We also
      performed single-marked GWAS using PLINK for TG levels (log-transformed).
      Significant associations were found between ASTN2 gene SNPs and plasma
      triglyceride levels (rs7035794, P = 2.24*10-10). Our study suggested that vitamin
      anabolism pathway, BCL6 gene pathways and ASTN2 gene may contribute to the
      genetic variation of plasma triglyceride concentrations. 

PMID- 26308952
TI  - Conditional Survival in de novo Metastatic Urothelial Carcinoma.
AB  - BACKGROUND: Second-line therapy is frequently utilized for metastatic urothelial
      carcinoma, but there are limited data to guide this approach. While an assessment
      of overall survival based on registry data may not capture the impact of second-
      and third-line therapies on clinical outcome, this may be reflected in relative
      conditional survival (RCS). METHODS: Patients with stage IV urothelial carcinoma
      diagnosed from 1990-2010 were identified from the Surveillance, Epidemiology and
      End Results (SEER) dataset. The association of clinicopathologic variables with
      disease specific survival (DSS) was explored through univariate and multivariate
      analyses. DSS in subgroups divided by time period (1990-2000 v 2001-2010) was
      compared using the Kaplan-Meier method and log-rank test. One-year RCS at annual
      landmarks up to 5 years was compared in subgroups divided by time period.
      RESULTS: Of 261,987 patients diagnosed with urothelial carcinoma from 1990-2010,
      3,110 patients met criteria for the current analysis. Characteristics of patients
      diagnosed between 1990 and 2000 (n = 810) and 2001 to 2010 (n = 2,300) were
      similar and there was no significant difference in DSS between the two groups. On
      multivariate analysis, older age (age >= 80) was associated with shorter DSS (HR
      1.79, 95%CI 1.48-2.15), but no association was found between time period of
      diagnosis and outcome. One-year RCS improved substantially through successive
      annual landmarks up to 5 years, but no differences were seen in subgroups divided
      by time of diagnosis. CONCLUSIONS: No difference in RCS was observed amongst
      patients with stage IV urothelial carcinoma diagnosed from 1990-2000 and 2001
      2010. A lack of difference in RCS (more so than cumulative DSS) may reflect a
      lack of progress in salvage therapies for the disease.

PMID- 26308953
TI  - A screening model for oral cancer using risk scores: development and validation.
AB  - OBJECTIVE: A study was conducted to develop and validate a screening model using
      risk scores to identify individuals at high risk for developing oral cancer in an
      Indian population. METHODS: Life-course data collected from a multicentre case
      control study in India were used. Interview was conducted to collect information
      on predictors limited to the time before the onset of symptoms or cancer
      diagnosis. Predictors included statistically significant risk factors in the
      multivariable model. A risk score for each predictor was derived from respective
      odds ratios (OR). Discrimination of the final model, risk scores and various risk
      score cut-offs was examined using the c statistic. The optimal cut-off was
      determined as the one with good area under curve (AUC) and high sensitivity.
      Predictive ability of the regression model and cut-off risk score was determined
      by calculating sensitivity, specificity, positive predictive value (PPV) and
      negative predictive value (NPV). Models were validated from a bootstrap sample.
      RESULTS: Smoking, chewing quid and/or tobacco, alcohol, a family history of upper
      aero-digestive tract cancer, diet and oral hygiene behaviour were the predictors.
      Risk scores ranged from 0 to 28. Area under the receiver operating characteristic
      (ROC) curve for risk scores was good (0.866). The sensitivity (0.928) and
      negative predictive value (0.927) were high, while specificity (0.603) and
      positive predictive value (0.607) were low for a risk score cut-off of 6.
      CONCLUSION: A risk score model to screen for individuals with high risk of oral
      cancer with satisfactory predictive ability was developed in the Indian
      population. Validation of the model in other populations is necessary before it
      can be recommended to identify subgroups of the population to be directed towards
      more extensive clinical evaluation.

PMID- 26308957
TI  - Polyurethane: Stable Cell Phenotype Requires Plasticity: Polymer Supported
      Directed Differentiation Reveals a Unique Gene Signature Predicting Stable
      Hepatocyte Performance (Adv. Healthcare Mater. 12/2015).
AB  - One major obstacle to the routine deployment of stem cell-derived cells is their
      instability in culture. On page 1820 David C. Hay and co-workers describe the use
      of a synthetic polymer surface. The image shows stem cell-derived hepatocytes
      replated on this polyurethane surface. Importantly the cells express Zonal
      Occludin (green stain) at the cell surface, which indicates that the cells
      display elements of polarization. The blue stain is DAPI, which demarks the
      nucleus. 

PMID- 26308960
TI  - Oral lichenoid reactions, patch tests, and mercury dental amalgam.

PMID- 26308962
TI  - Simultaneous Aggregation and Height Bifurcation of Colloidal Particles near
      Electrodes in Oscillatory Electric Fields.
AB  - Micrometer-scale particles suspended in NaCl solutions aggregate laterally near
      the electrode upon application of a low-frequency (~100 Hz) field, but the same
      particles suspended in NaOH solutions are instead observed to separate laterally.
      The underlying mechanism for the electrolyte dependence remains obscure. Recent
      work by Woehl et al. (PRX, 2015) revealed that, contrary to previous reports,
      particles suspended in NaOH solutions indeed aggregate under some conditions
      while simultaneously exhibiting a distinct bifurcation in average height above
      the electrode. Here we elaborate on this observation by demonstrating the
      existence of a critical frequency (~25 Hz) below which particles in NaOH
      aggregate laterally and above which they separate. The results indicate that the
      current demarcation of electrolytes as either aggregating or separating is
      misleading and that the key role of the electrolyte instead is to set the
      magnitude of a critical frequency at which particles transition between the two
      behaviors. 

PMID- 26308961
TI  - Utilization of catheter-directed thrombolysis in pulmonary embolism and outcome
      difference between systemic thrombolysis and catheter-directed thrombolysis.
AB  - OBJECTIVE: The aim of the study was to assess the utilization of catheter
      directed thrombolysis (CDT) and its comparative effectiveness against systemic
      thrombolysis in acute pulmonary embolism (PE). BACKGROUND: Contemporary real
      world data regarding utilization and outcomes comparing systemic thrombolysis
      with CDT for PE is sparse. METHODS: We queried the Nationwide Inpatient Sample
      from 2010 to 2012 using the ICD-9-CM diagnosis code 415.11, 415.13, and 415.19
      for acute PE. We used propensity score analysis to compare outcomes between
      systemic thrombolysis and CDT. Primary outcome was in-hospital mortality.
      Secondary outcome was combined in-hospital mortality and intracranial hemorrhage
      (ICH). RESULTS: Out of 110,731 patients hospitalized with PE, we identified 1,521
      patients treated with thrombolysis, of which 1,169 patients received systemic
      thrombolysis and 352 patients received CDT. After propensity-matched comparison,
      primary and secondary outcomes were significantly lower in the CDT group compared
      to systemic thrombolysis (21.81% vs. 13.36%, OR 0.55, 95% CI 0.36-0.85, P value =
      0.007) and (22.89% vs. 13.36%, OR 0.52, 95% CI 0.34-0.80, P value = 0.003),
      respectively. The median length of stay [7 days, interquartile range (IQR) (5-9
      days) vs. 7 days, IQR (5-10 days), P = 0.17] was not significant between the two
      groups. The CDT group had higher cost of hospitalization [$17,218, IQR ($12,272
      $23,906) vs. $23,799, IQR ($17,892-$35,338), P < 0.001]. Multivariate analysis
      identified increasing age, saddle PE, cardiopulmonary arrest, and Medicaid
      insurance as independent predictors of in-hospital mortality. CONCLUSIONS: CDT
      was associated with lower in-hospital mortality and combined in-hospital
      mortality and ICH.

PMID- 26308963
TI  - Membrane receptor-dependent Notch1/Hes1 activation by melatonin protects against
      myocardial ischemia-reperfusion injury: in vivo and in vitro studies.
AB  - Melatonin confers profound protective effect against myocardial ischemia
      reperfusion injury (MI/RI). Activation of Notch1/Hairy and enhancer of split 1
      (Hes1) signaling also ameliorates MI/RI. We hypothesize that melatonin attenuates
      MI/RI-induced oxidative damage by activating Notch1/Hes1 signaling pathway with
      phosphatase and tensin homolog deleted on chromosome 10 (Pten)/Akt acting as the
      downstream signaling pathway in a melatonin membrane receptor-dependent manner.
      Male Sprague Dawley rats were treated with melatonin (10 mg/kg/day) for 4 wk and
      then subjected to MI/R surgery. Melatonin significantly improved cardiac function
      and decreased myocardial apoptosis and oxidative damage. Furthermore, in cultured
      H9C2 cardiomyocytes, melatonin (100 MUmol/L) attenuated simulated ischemia
      reperfusion (SIR)-induced myocardial apoptosis and oxidative damage. Both in vivo
      and in vitro study demonstrated that melatonin treatment increased Notch1, Notch1
      intracellular domain (NICD), Hes1, Bcl-2 expressions, and p-Akt/Akt ratio and
      decreased Pten, Bax, and caspase-3 expressions. However, these protective effects
      conferred by melatonin were blocked by DAPT (the specific inhibitor of Notch1
      signaling), luzindole (the antagonist of melatonin membrane receptors), Notch1
      siRNA, or Hes1 siRNA administration. In summary, our study demonstrates that
      melatonin treatment protects against MI/RI by modulating Notch1/Hes1 signaling in
      a receptor-dependent manner and Pten/Akt signaling pathways are key downstream
      mediators.

PMID- 26308965
TI  - Corrigendum.

PMID- 26308964
TI  - Integrated methylome and transcriptome analysis reveals novel regulatory elements
      in pediatric acute lymphoblastic leukemia.
AB  - Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in
      children under the age of 15. In addition to genetic aberrations, epigenetic
      modifications such as DNA methylation are altered in cancer and impact gene
      expression. To identify epigenetic alterations in ALL, genome-wide methylation
      profiles were generated using the methylated CpG island recovery assay followed
      by next-generation sequencing. More than 25,000 differentially methylated regions
      (DMR) were observed in ALL patients with ~ 90% present within intronic or
      intergenic regions. To determine the regulatory potential of the DMR, whole
      transcriptome analysis was performed and integrated with methylation data.
      Aberrant promoter methylation was associated with the altered expression of genes
      involved in transcriptional regulation, apoptosis, and proliferation. Novel
      enhancer-like sequences were identified within intronic and intergenic DMR.
      Aberrant methylation in these regions was associated with the altered expression
      of neighboring genes involved in cell cycle processes, lymphocyte activation and
      apoptosis. These genes include potential epi-driver genes, such as SYNE1, PTPRS,
      PAWR, HDAC9, RGCC, MCOLN2, LYN, TRAF3, FLT1, and MELK, which may provide a
      selective advantage to leukemic cells. In addition, the differential expression
      of epigenetic modifier genes, pseudogenes, and non-coding RNAs was also observed
      accentuating the role of erroneous epigenetic gene regulation in ALL.

PMID- 26308967
TI  - How many individuals will need to be screened to increase colorectal cancer
      screening prevalence to 80% by 2018?
AB  - BACKGROUND: A recent study estimates that 277,000 colorectal cancer (CRC) cases
      and 203,000 CRC deaths will be averted between 2013 and 2030 if the National
      Colorectal Cancer Roundtable goal of increasing CRC screening prevalence to 80%
      by 2018 is reached. However, the number of individuals who need to be screened
      (NNS) to achieve this goal is unknown. In this communication, the authors
      estimate the NNS to achieve 80% by 2018 nationwide and by state. METHODS: The
      authors estimated the NNS by subtracting adults aged 50 to 75 years who would
      need to be screened to achieve an 80% CRC screening prevalence from the number
      who are currently guideline-compliant from population estimates for this age
      group. The 2013 National Health Interview Survey and the 2012 Behavioral Risk
      Factor Surveillance System were used to estimate CRC screening prevalence and
      data from the US Census Bureau were used to estimate population projections. The
      NNS were age-standardized and sex-standardized. RESULTS: Nationwide, 24.39
      million individuals (95% confidence interval, 24.37-24.41 million) aged 50 to 75
      years will need to be screened to achieve 80% by 2018. By state, the NNS ranged
      from 45,400 in Vermont to 2.72 million in California. The majority of individuals
      who need to be screened are aged 50 to 64 years and the largest subgroup is
      privately insured. CONCLUSIONS: The authors estimated that at least 24.4 million
      additional individuals in the United States will need to be screened to achieve
      the National Colorectal Cancer Roundtable goal of increasing CRC screening
      prevalence to 80% by 2018. To reach this goal, improving facilitators of CRC
      screening, including physician recommendation and patient awareness, is needed.

PMID- 26308968
TI  - Estimation of noise properties for TV-regularized image reconstruction in
      computed tomography.
AB  - A method for predicting the image covariance resulting from total-variation
      penalized iterative image reconstruction (TV-penalized IIR) is presented and
      demonstrated in a variety of contexts. The method is validated against the sample
      covariance from statistical noise realizations for a small image using a variety
      of comparison metrics. Potential applications for the covariance approximation
      include investigation of image properties such as object- and signal-dependence
      of noise, and noise stationarity. These applications are demonstrated, along with
      the construction of image pixel variance maps for two-dimensional 128 * 128 pixel
      images. Methods for extending the proposed covariance approximation to larger
      images and improving computational efficiency are discussed. Future work will
      apply the developed methodology to the construction of task-based image quality
      metrics such as the Hotelling observer detectability for TV-based IIR.

PMID- 26308970
TI  - Anion Receptor Design: Exploiting Outer-Sphere Coordination Chemistry To Obtain
      High Selectivity for Chloridometalates over Chloride.
AB  - High anion selectivity for PtCl6(2-) over Cl(-) is shown by a series of
      amidoamines, R(1)R(2)NCOCH2CH2NR(3)R(4) (L1 with R(1) = R(4) = benzyl and R(2) =
      R(3) = phenyl and L3 with R(1) = H, R(2) = 2-ethylhexyl, R(3) = phenyl and R(4) =
      methyl), and amidoethers, R(1)R(2)NCOCH2CH2OR(3) (L5 with R(1) = H, R(2) = 2
      ethylhexyl and R(3) = phenyl), which provide receptor sites which extract PtCl6(2
      ) preferentially over Cl(-) in extractions from 6 M HCl solutions. The amidoether
      receptor L5 was found to be a much weaker extractant for PtCl6(2-) than its
      amidoamine analogues. Density functional theory calculations indicate that this
      is due to the difficulty in protonating the amidoether to generate a cationic
      receptor, LH(+), rather than the latter showing weaker binding to PtCl6(2-). The
      most stable forms of the receptors, LH(+), contain a tautomer in which the added
      proton forms an intramolecular hydrogen bond to the amide oxygen atom to give a
      six-membered proton chelate. Dispersion-corrected DFT calculations appear to
      suggest a switch in ligand conformation for the amidoamine ligands to an open
      tautomer state in the complex, such that the cationic N-H or O-H groups are also
      readily available to form hydrogen bonds to the PtCl6(2-) ion, in addition to the
      array of polarized C-H bonds. The predicted difference in energies between the
      proton chelate and nonchelated tautomer states for L1 is small, however, and the
      former is found in the X-ray crystal structure of the assembly [(L1H)2PtCl6]. The
      DFT calculations and the X-ray structure indicate that all LH(+) receptors
      present an array of polarized C-H groups to the large, charge diffuse PtCl6(2-)
      anion resulting in high selectivity of extraction of PtCl6(2-) over the large
      excess of chloride. 

PMID- 26308969
TI  - Wheelchair-specific fitness of persons with a long-term spinal cord injury: cross
      sectional study on effects of time since injury and physical activity level.
AB  - PURPOSE: To study the impact of time since injury (TSI) and physical activity
      (PA) on fitness of persons with spinal cord injury (SCI). METHOD: Cross-sectional
      study. Persons with SCI (N = 158) in three TSI strata: 10-19, 20-29 and >=30
      years after SCI and divided in an active and inactive group. Fitness [peak power
      output (POpeak) and peak oxygen uptake (VO2peak)] was assessed. RESULTS: In
      persons with tetraplegia, no significant relationship was found between TSI and
      fitness after controlling for confounders, while a higher activity level was
      related to a higher POpeak in this group. Active people with tetraplegia also
      showed less decline in POpeak with an increase in TSI compared to inactive
      people. In persons with paraplegia, after controlling for confounders, it was
      shown that TSI had a negative effect on POpeak, while PA was not significantly
      associated with fitness in people with paraplegia. CONCLUSIONS: In people with
      paraplegia, fitness was significantly lower in those with a longer TSI. Persons
      with a long TSI might need more attention to remain fit and PA might be an
      important element in that respect as shown by the results of the group with a
      tetraplegia. IMPLICATIONS FOR REHABILITATION: Wheelchair-specific fitness seems
      to diminish over time after paraplegia. An active lifestyle is related to
      wheelchair-specific fitness in persons with tetraplegia. Prevention of long-term
      deconditioning is very important.

PMID- 26308966
TI  - Early Cannabis Use, Polygenic Risk Score for Schizophrenia and Brain Maturation
      in Adolescence.
AB  - IMPORTANCE: Cannabis use during adolescence is known to increase the risk for
      schizophrenia in men. Sex differences in the dynamics of brain maturation during
      adolescence may be of particular importance with regard to vulnerability of the
      male brain to cannabis exposure. OBJECTIVE: To evaluate whether the association
      between cannabis use and cortical maturation in adolescents is moderated by a
      polygenic risk score for schizophrenia. DESIGN, SETTING, AND PARTICIPANTS:
      Observation of 3 population-based samples included initial analysis in 1024
      adolescents of both sexes from the Canadian Saguenay Youth Study (SYS) and follow
      up in 426 adolescents of both sexes from the IMAGEN Study from 8 European cities
      and 504 male youth from the Avon Longitudinal Study of Parents and Children
      (ALSPAC) based in England. A total of 1577 participants (aged 12-21 years; 899
      [57.0%] male) had (1) information about cannabis use; (2) imaging studies of the
      brain; and (3) a polygenic risk score for schizophrenia across 108 genetic loci
      identified by the Psychiatric Genomics Consortium. Data analysis was performed
      from March 1 through December 31, 2014. MAIN OUTCOMES AND MEASURES: Cortical
      thickness derived from T1-weighted magnetic resonance images. Linear regression
      tests were used to assess the relationships between cannabis use, cortical
      thickness, and risk score. RESULTS: Across the 3 samples of 1574 participants, a
      negative association was observed between cannabis use in early adolescence and
      cortical thickness in male participants with a high polygenic risk score. This
      observation was not the case for low-risk male participants or for the low- or
      high-risk female participants. Thus, in SYS male participants, cannabis use
      interacted with risk score vis-a-vis cortical thickness (P = .009); higher scores
      were associated with lower thickness only in males who used cannabis. Similarly,
      in the IMAGEN male participants, cannabis use interacted with increased risk
      score vis-a-vis a change in decreasing cortical thickness from 14.5 to 18.5 years
      of age (t137 = -2.36; P = .02). Finally, in the ALSPAC high-risk group of male
      participants, those who used cannabis most frequently (>=61 occasions) had lower
      cortical thickness than those who never used cannabis (difference in cortical
      thickness, 0.07 [95% CI, 0.01-0.12]; P = .02) and those with light use (<5
      occasions) (difference in cortical thickness, 0.11 [95% CI, 0.03-0.18]; P =
      .004). CONCLUSIONS AND RELEVANCE: Cannabis use in early adolescence moderates the
      association between the genetic risk for schizophrenia and cortical maturation
      among male individuals. This finding implicates processes underlying cortical
      maturation in mediating the link between cannabis use and liability to
      schizophrenia.

PMID- 26308971
TI  - A Novel Continuous Assay for the Deacylase Sirtuin 5 and Other Deacetylases.
AB  - Sirtuins are NAD(+) dependent lysine deacylases involved in many regulatory
      processes like control of metabolic pathways, DNA repair, and stress response.
      Modulators of sirtuin activity are needed as tools for uncovering the biological
      function of these enzymes and as potential therapeutics. Systematic discovery of
      such modulators is hampered by the lack of efficient and simple continuous
      activity assays running at low sirtuin concentrations in microtiter plates. Here
      we describe an improved continuous sirtuin 5 assay based on the coupling of the
      sirtuin reaction to a proteolytic cleavage using internally fluorescence-quenched
      substrates. Systematic optimization of a carbamoyl phosphate synthetase 1
      derived, glutarylated peptide yielded a Sirt5 substrate with k(cat)/K(M) value of
      337,000 M(-1) s(-1), which represents the best sirtuin substrate described so
      far. These extraordinary substrate properties allowed reliable determination of
      Ki values for different inhibitors in the presence of only 10 nM sirtuin in
      microtiter plate format. Assay conditions could be transferred effectively to
      other lysine deacetylases, like sirtuin 2 and sirtuin 3, which now enables more
      efficient development of sirtuin targeting drugs.

PMID- 26308972
TI  - Fabricating Upconversion Fluorescent Probes for Rapidly Sensing Foodborne
      Pathogens.
AB  - Rare earth-doped upconversion nanoparticles (UCNPs) have promising potential in
      the field of food safety because of their unique frequency upconverting
      capability and high detection sensitivity. Here, we report a rapid and sensitive
      UCNP-based bacterium-sensing strategy using Escherichia coli. Highly fluorescent
      and water-soluble UCNPs were fabricated and conjugated with antibodies against E.
      coli for use as fluorescent probes. The E. coli were successively captured by the
      fluorescent probes. After the captured cell samples were pelleted, the
      differences in the fluorescence intensities between sample supernatants and the
      control were observed to increase linearly with E. coli concentration from 42 to
      42 * 10(6) colony-forming units (cfu)/mL (R(2) = 0.9802), resulting in a
      relatively low limit of detection of 10 cfu/mL. Furthermore, the ability of the
      bioassay to detect E. coli was also confirmed in adulterated meat and milk
      samples. 

PMID- 26308974
TI  - Interlaboratory evaluation of cellulosic acid-soluble internal air sampling
      capsules for multi-element analysis.
AB  - An interlaboratory study was carried out to evaluate the use of acid-soluble
      cellulosic air sampling capsules for their suitability in the measurement of
      trace elements in workplace atmospheric samples. These capsules are used as
      inserts to perform closed-face cassette sample collection for occupational
      exposure monitoring. The interlaboratory study was performed in accordance with
      NIOSH guidelines that describe statistical procedures for evaluating measurement
      accuracy of air monitoring methods. The performance evaluation materials used
      consisted of cellulose acetate capsules melded to mixed-cellulose ester filters
      that were dosed with multiple elements from commercial standard aqueous
      solutions. The cellulosic capsules were spiked with the following 33 elements of
      interest in workplace air monitoring: Ag, Al, As, Ba, Be, Ca, Cd, Co, Cr, Cu, Fe,
      In, K, La, Li, Mg, Mn, Mo, Ni, P, Pb, Sb, Se, Sn, Sr, Te, Ti, Tl, V, W, Y, Zn,
      Zr. The elemental loading levels were certified by an accredited provider of
      certified reference materials. Triplicates of media blanks and multielement
      spiked capsules at three different elemental loadings were sent to each
      participating laboratory; the elemental loading levels were not revealed to the
      laboratories. The volunteer participating laboratories were asked to prepare the
      samples by acid dissolution and to analyze aliquots of extracted samples by
      inductively coupled plasma atomic emission spectrometry in accordance with NIOSH
      methods. It was requested that the study participants report their analytical
      results in units of MUg of each target element per internal capsule sample. For
      the majority of the elements investigated (30 out of 33), the study accuracy
      estimates obtained satisfied the NIOSH accuracy criterion (A < 25%). This
      investigation demonstrates the utility of acid-soluble internal sampling capsules
      for multielement analysis by atomic spectrometry. 

PMID- 26308973
TI  - A critical role of temporoparietal junction in the integration of top-down and
      bottom-up attentional control.
AB  - Information processing can be biased toward behaviorally relevant and salient
      stimuli by top-down (goal-directed) and bottom-up (stimulus-driven) attentional
      control processes respectively. However, the neural basis underlying the
      integration of these processes is not well understood. We employed functional
      magnetic resonance imaging (fMRI) and transcranial direct-current stimulation
      (tDCS) in humans to examine the brain mechanisms underlying the interaction
      between these two processes. We manipulated the cognitive load involved in top
      down processing and stimulus surprise involved in bottom-up processing in a
      factorial design by combining a majority function task and an oddball paradigm.
      We found that high cognitive load and high surprise level were associated with
      prolonged reaction time compared to low cognitive load and low surprise level,
      with a synergistic interaction effect, which was accompanied by a greater
      deactivation of bilateral temporoparietal junction (TPJ). In addition, the TPJ
      displayed negative functional connectivity with right middle occipital gyrus,
      which is involved in bottom-up processing (modulated by the interaction effect),
      and the right frontal eye field (FEF), which is involved in top-down control. The
      enhanced negative functional connectivity between the TPJ and right FEF was
      accompanied by a larger behavioral interaction effect across subjects.
      Application of cathodal tDCS over the right TPJ eliminated the interaction
      effect. These results suggest that the TPJ plays a critical role in processing
      bottom-up information for top-down control of attention.

PMID- 26308975
TI  - ChR2 coming of age.

PMID- 26308976
TI  - How a fly escapes the reflex trap.

PMID- 26308977
TI  - GABA receptors in a state of fear.

PMID- 26308978
TI  - The changing tree in Parkinson's disease.

PMID- 26308979
TI  - Character studies.

PMID- 26308980
TI  - Optogenetics and the future of neuroscience.
AB  - Over the last 10 years, optogenetics has become widespread in neuroscience for
      the study of how specific cell types contribute to brain functions and brain
      disorder states. The full impact of optogenetics will emerge only when other
      toolsets mature, including neural connectivity and cell phenotyping tools and
      neural recording and imaging tools. The latter tools are rapidly improving, in
      part because optogenetics has helped galvanize broad interest in neurotechnology
      development. 

PMID- 26308981
TI  - Optogenetics: 10 years after ChR2 in neurons--views from the community.

PMID- 26308984
TI  - Access to Imidazo[1,2-a]pyridines via Annulation of alpha-Keto Vinyl Azides and 2
      Aminopyridines.
AB  - A novel strategy for the synthesis of imidazo[1,2-a]pyridines via efficient
      catalyst/metal-free annulations of alpha-keto vinyl azides and 2-aminopyridines
      is described. Several imidazo[1,2-a]pyridines were synthesized from readily
      available vinyl azides and 2-aminopyridines and obtained in highly pure form by
      simply evaporating the reaction solvent. This remarkably high yielding and atom
      economical protocol allows the formation of three new C-N bonds through cascade
      reactions and rearrangements. 

PMID- 26308983
TI  - Modifiers of C9orf72 dipeptide repeat toxicity connect nucleocytoplasmic
      transport defects to FTD/ALS.
AB  - C9orf72 mutations are the most common cause of amyotrophic lateral sclerosis
      (ALS) and frontotemporal dementia (FTD). Dipeptide repeat proteins (DPRs)
      produced by unconventional translation of the C9orf72 repeat expansions cause
      neurodegeneration in cell culture and in animal models. We performed two unbiased
      screens in Saccharomyces cerevisiae and identified potent modifiers of DPR
      toxicity, including karyopherins and effectors of Ran-mediated nucleocytoplasmic
      transport, providing insight into potential disease mechanisms and therapeutic
      targets. 

PMID- 26308985
TI  - Validity of Torque-Data Collection at Multiple Sites: A Framework for
      Collaboration on Clinical-Outcomes Research in Sports Medicine.
AB  - CONTEXT: Collecting torque data using a multimode dynamometer is common in sports
      medicine research. The error in torque measurements across multiple sites and
      dynamometers has not been established. OBJECTIVE: To assess the validity of 2
      calibration protocols across 3 dynamometers and the error associated with torque
      measurement for each system. DESIGN: Observational study. SETTING: 3 university
      laboratories at separate institutions. EQUIPMENT: 2 Biodex System 3 dynamometers
      and 1 Biodex System 4 dynamometer. INTERVENTIONS: System calibration was
      completed using the manufacturer-recommended single-weight method and an
      experimental calibration method using a series of progressive weights. Both
      calibration methods were compared with a manually calculated theoretical torque
      across a range of applied weights. MAIN OUTCOME MEASURES: Relative error,
      absolute error, and percent error were calculated at each weight. Each outcome
      variable was compared between systems using 95% confidence intervals across low
      (0-65 Nm), moderate (66-110 Nm), and high (111-165 Nm) torque categorizations.
      RESULTS: Calibration coefficients were established for each system using both
      calibration protocols. However, within each system the calibration coefficients
      generated using the single-weight (System 4 = 2.42 [0.90], System 3a = 1.37
      [1.11], System 3b = -0.96 [1.45]) and experimental calibration protocols (System
      4 = 3.95 [1.08], System 3a = -0.79 [1.23], System 3b = 2.31 [1.66]) were similar
      and displayed acceptable mean relative error compared with calculated theoretical
      torque values. Overall, percent error was greatest for all 3 systems in low
      torque conditions (System 4 = 11.66% [6.39], System 3a = 6.82% [11.98], System 3b
      = 4.35% [9.49]). The System 4 significantly overestimated torque across all 3
      weight increments, and the System 3b overestimated torque over the moderate
      torque increment. CONCLUSIONS: Conversion of raw voltage to torque values using
      the single-calibration-weight method is valid and comparable to a more complex
      multiweight calibration process; however, it is clear that calibration must be
      done for each individual system to ensure accurate data collection.

PMID- 26308986
TI  - Tripeptides on Gold Nanoparticles: Structural Differences between Two Reverse
      Sequences as Determined by Solid-State NMR and DFT Calculations.
AB  - The reverse-sequence peptides CysAlaAla and AlaAlaCys may attach to gold
      nanoparticles through the thiol group, and they differ primarily by whether the
      charged amino or the carboxylate group is proximal to the sulfur. Alanine
      residues in these peptides are not expected to interact significantly with the
      gold surface and serve to place a large separation between the amino and
      carboxylate groups. Solid-state NMR experiments and DFT calculations were
      performed to explore the structural differences between CysAlaAla on gold
      nanoparticles and AlaAlaCys on gold nanoparticles. It is found that the relative
      positions between the thiol, amino, and carboxylate groups strongly influences
      the structures of the peptide-gold systems. CysAlaAla orients parallel to the
      gold surface in a monolayer fashion, whereas AlaAlaCys forms an interdigitating
      bilayer-like structure that is oriented upright relative to the gold surface. 

PMID- 26308987
TI  - Time for strong leadership.
AB  - 'Achievable, desirable and realistic': that's the verdict of Nursing and
      Midwifery Council (NMC) chief executive Jackie Smith on revalidation as care
      providers prepare to introduce it across the UK. 

PMID- 26308982
TI  - Optogenetics: 10 years of microbial opsins in neuroscience.
AB  - Over the past 10 years, the development and convergence of microbial opsin
      engineering, modular genetic methods for cell-type targeting and optical
      strategies for guiding light through tissue have enabled versatile optical
      control of defined cells in living systems, defining modern optogenetics. Despite
      widespread recognition of the importance of spatiotemporally precise causal
      control over cellular signaling, for nearly the first half (2005-2009) of this 10
      year period, as optogenetics was being created, there were difficulties in
      implementation, few publications and limited biological findings. In contrast,
      the ensuing years have witnessed a substantial acceleration in the application
      domain, with the publication of thousands of discoveries and insights into the
      function of nervous systems and beyond. This Historical Commentary reflects on
      the scientific landscape of this decade-long transition. 

PMID- 26308989
TI  - Registrants need simple advice to help them navigate revalidation.
AB  - NURSES AND midwives need guidance about revalidation to be made more
      straightforward if the planned new system is to work smoothly. 

PMID- 26308988
TI  - Patient care may be at risk from tired staff on long shifts.
AB  - THE RISE in 12-hour shifts is placing nurses at greater risk of fatigue, making
      errors and jeopardising patient safety, new research warns. 

PMID- 26308993
TI  - Nursing directors urged to join safe staffing group.
AB  - ENGLAND'S CHIEF nurse Jane Cummings has written to nursing directors inviting
      them to become part of an expert group on safe staffing. 

PMID- 26308994
TI  - Strong leadership needed to ensure NHS makes savings.
AB  - LEADERSHIP AND management in the NHS have been put at the centre of government
      plans for the health service during this parliament. 

PMID- 26308995
TI  - Striving to make births safer.
AB  - IT IS eight years since nurse leader Chinomnso Ibe established the Traffina
      Foundation for Community Health (TFCH), a non-profit organisation that helps to
      reduce the high number of deaths from complications during pregnancy and delivery
      in Nigeria, her home country. 

PMID- 26308996
TI  - Disseminating good practice.
AB  - COMMUNICATION IS a core competency for nurse executives. Being able to write well
      and share this writing through publication is essential to disseminate
      information, engender support and share a vision. 

PMID- 26308997
TI  - Susan Williams - International outlook.
AB  - IT IS always great to see nurse-led innovations championed beyond the immediate
      nursing community. The latest import from the Netherlands to have caught the
      attention of UK health and social care providers and commissioners is the
      Buurtzorg model. 

PMID- 26309001
TI  - Feedback is valuable.
AB  - AS A senior manager in the nursing team at the Evelina London Children's
      Hospital, I fully appreciate the importance of revalidation. This is a big change
      for the profession so it is crucial to ensure that it works well for registrants
      and, most importantly, that it is effective in promoting high-quality care for
      patients. 

PMID- 26309002
TI  - Taking time to make connections.

PMID- 26309004
TI  - Overseas fellowships.
AB  - Applications are open for the 2016 Winston Churchill Fellowship programme, which
      enables successful applicants to travel overseas to examine best practice and
      innovative programmes, then return to the UK and disseminate these ideas. 

PMID- 26309005
TI  - Clinical careers film.
AB  - Those interested in developing clinical academic careers might be interested in a
      short animated film by Health Education England (HEE) and the National Institute
      for Health Research. The three-minute film, a frame from which is shown below,
      describes the sort of opportunities that are on offer to all professionals as
      part of the HEE's clinical academic careers framework. You can view the film on
      YouTube at tinyurl.com/pelb95c. 

PMID- 26309006
TI  - Revalidation.
AB  - The NMC has also developed two online tools to help nurses and midwives identify
      who can confirm that they have demonstrated compliance with the revalidation
      requirements, and to help employers provide the support employees require for
      effective revalidation. The NMC recommends that a line manager provides
      revalidation, but this person does not have to be an NMC-registered nurse or
      midwife. The online resource for employers outlines how to support nurse and
      midwife revalidation and is available at tinyurl.com/pycknzu. 

PMID- 26309007
TI  - Housing and health.
AB  - NHS Alliance has collaborated with the housing sector to develop a new online
      resource to support its Health Begins at Home initiative, which seeks to clarify
      the correlation between housing and health. 

PMID- 26309008
TI  - Duty of candour.
AB  - New guidance from the Nursing and Midwifery Council (NMC), in collaboration with
      the General Medical Council, sets out the standards expected of all nurses,
      midwives and doctors practising in the UK in relation to the professional duty of
      candour. 

PMID- 26309009
TI  - Employee health.
AB  - The National Institute for Health and Care Excellence has produced a new
      guideline looking at improving the health and wellbeing of employees, with a
      particular focus on organisational culture and context, and the role of line
      managers. 

PMID- 26309010
TI  - Staff performance.
AB  - To support senior nurses and other health service leaders who face the challenge
      of performance management as part of their role, NHS Employers, in partnership
      with the National Skills Academy for Social Care, has launched a new toolkit. 

PMID- 26309011
TI  - Measuring the quality of nutritional care.
AB  - Despite various campaigns and initiatives, and publication of numerous standards,
      malnutrition in healthcare settings often goes unrecognised and untreated. This
      negatively affects patients' experiences and outcomes, and has financial
      implications for the NHS. The British Association for Parenteral and Enteral
      Nutrition has launched a new online tool that helps trusts measure the quality of
      the nutritional care they provide. This article describes the tool and explains
      its structure, how organisations and nurses can access and use it, and the
      benefits of implementing this resource as a routine part of clinical care. 

PMID- 26309012
TI  - Revalidation: a university health board's learning from pilot partner engagement.
AB  - This article aims to share organisational experiences and learning from the
      largest Nursing and Midwifery Council (NMC) revalidation pilot partner. The
      purpose of revalidation is to improve public and patient protection through
      career-long professional updating. Pilot participation enabled Aneurin Bevan
      University Health Board (ABUHB) to contribute significantly to system and process
      testing, underpinning revalidation across a range of nursing and midwifery
      settings. An action plan was developed providing a structured approach to the
      revalidation pilot, detailed actions were identified and progress against actions
      mapped and reported. While revalidation is the individual registrant's
      responsibility, there is an organisational obligation to create a supportive
      enabling environment. A strategic plan incorporating revalidation into
      organisational objectives and structured leadership roles assisted registrants to
      successfully meet the NMC's requirements. With 813 registrants completing the
      pilot process, ABUHB has an enhanced understanding of the revalidation process
      and an appreciation of its impact on associated professional issues. This level
      of learning has increased readiness for revalidation commencement for all UK
      nurses and midwives. 

PMID- 26309013
TI  - Caring for children with complex needs.
AB  - This article describes the role of the community neonatal nurse in the discharge
      of infants with chronic lung disease (CLD), or bronchopulmonary dysplasia. It
      also explores the use of a common assessment framework in the assessment of such
      children and development of a nursing care plan. The article includes a case
      study to illustrate the link between CLD and other diseases, and emphasises the
      importance of focusing on holistic care from admission, in the neonatal unit and
      at discharge. 

PMID- 26309014
TI  - A true passion.
AB  - When Eileen Fegan was five years old, back when visiting was an hour a day, she
      had her adenoids removed at East Birmingham Hospital, now Heartlands Hospital. 

PMID- 26309015
TI  - Characteristics of PCR-SSCP and RAPD-HPCE methods for identifying authentication
      of Penis et testis cervi in Traditional Chinese Medicine based on cytochrome b
      gene.
AB  - The use of Penis et testis cervi, as a kind of precious Traditional Chinese
      Medicine (TCM), which is derived from dry deer's testis and penis, has been
      recorded for many years in China. There are abundant species of deer in China,
      the Penis et testis from species of Cervus Nippon and Cervus elaphusL were
      authentic, others species were defined as adulterant (different subspecies of
      deer) or counterfeits (different species). Identification of their origins or
      authenticity becomes a key in controlling the herbal products. A modified column
      chromatography was used to extract mitochondrial DNA of dried deer's testis and
      penis from sika deer (C. Nippon) and red deer (C. elaphusL) in addition to
      adulterants and counterfeits. Column chromatography requires for a short time to
      extract mitochondrial DNA of high purity with little damage of DNA molecules,
      which provides the primary structure of guarantee for the specific PCR; PCR-SSCP
      method showed a clear intra-specific difference among patterns of single-chain
      fragments, and completely differentiate Penis et testis origins from C. Nippon
      and C. elaphusL. RAPD-HPCE was based on the standard electropherograms to compute
      a control spectrum curve as similarity reference (R) among different samples. The
      similarity analysis indicated that there were significant inter-species
      differences among Penis et testis' adulterant or counterfeits. Both techniques
      provide a fast, simple, and accurate way to directly identify among inter-species
      or intra-species of Penis et testis.

PMID- 26309017
TI  - DeSUMOylation: An Important Therapeutic Target and Protein Regulatory Event.
AB  - The discovery of the process of small ubiquitin-like modifier (SUMO)-mediated
      post-translational modification of targets (SUMOylation) in early 1990s proved to
      be a significant step ahead in understanding mechanistic regulation of proteins
      and their functions in diverse life processes at the cellular level. The critical
      step in reversing the SUMOylation pathway is its ability to be dynamically
      deSUMOylated by SUMO/sentrin-specific protease (SENP). This review is intended to
      give a brief introduction about the process of SUMOylation, different mammalian
      deSUMOylating enzymes with special emphasis on their regulation of ribosome
      biogenesis at the molecular level, and its emerging roles in mitochondrial
      dynamics that might reveal usefulness of SENPs for therapeutic applications. 

PMID- 26309016
TI  - AFM single-cell force spectroscopy links altered nuclear and cytoskeletal
      mechanics to defective cell adhesion in cardiac myocytes with a nuclear lamin
      mutation.
AB  - Previous investigations suggested that lamin A/C gene (LMNA) mutations, which
      cause a variety of human diseases including muscular dystrophies and
      cardiomyopathies, alter the nuclear mechanical properties. We hypothesized that
      biomechanical changes may extend beyond the nucleus. 

PMID- 26309018
TI  - Effect of Regulatory T Cells on Promoting Apoptosis of T Lymphocyte and Its
      Regulatory Mechanism in Sepsis.
AB  - With both in vivo and in vitro experiments, the present study was conducted to
      investigate the effect of regulatory T cell (Treg) on promoting T-lymphocyte
      apoptosis and its regulatory mechanism through transforming growth factor-beta
      (TGF-beta1) signaling in mice. A murine model of polymicrobial sepsis was
      reproduced by cecal ligation and puncture (CLP); PC61 and anti-TGF-beta
      antibodies were used to decrease counts of CD4(+)CD25(+) Tregs and inhibit TGF
      beta activity, respectively. Splenic CD4(+)CD25(+) Tregs and CD4(+)CD25(-) T
      cells were isolated. Phenotypes, including cytotoxic T-lymphocyte-associated
      antigen 4 (CTLA-4), forkhead/winged helix transcription factor p3 (Foxp3), and
      TGFbeta1(m+), as well as the apoptotic rate of CD4(+)CD25(-) T cell, were
      analyzed by flow cytometry. Real-time reverse transcription-polymerase chain
      reaction was performed to determine mRNA expression of TGF-beta1, and the
      expressions of Smad2/Smad3, Bcl-2 superfamily members of Bcl-2/Bim, cytochrome C,
      the mitochondrial membrane potential, and caspases in CD4(+)CD25(-) T cells were
      simultaneously determined. After treatment with PC61 or anti-TGF-beta antibody,
      CTLA-4, Foxp3, and TGFbeta1(m+) expressions of CD4(+)CD25(+) Tregs were markedly
      decreased in comparison to that of the CLP group and the apoptosis rate of
      CD4(+)CD25(-) T cells was significantly positively correlated with the expression
      of TGF-beta1. Meanwhile, levels of P-Smad2/P-Smad3, proapoptotic protein Bim,
      cytochrome C, and activity of caspase-3, -8, -9 were downregulated, whereas the
      mitochondrial membrane potential and antiapoptotic protein Bcl-2 expression were
      restored. Taken together, our data indicated that the TGF-beta1 signal could be
      partly involved in the apoptosis of CD4(+)CD25(-) T cells promoted by
      CD4(+)CD25(+) Tregs, therefore inhibition of TGF-beta1 expression may provide a
      novel strategy for the improvement of host immunosuppression following sepsis. 

PMID- 26309019
TI  - The Association Between Sjogren Syndrome and Adverse Postoperative Outcomes: A
      Historical Cohort Study Using Administrative Health Data.
AB  - BACKGROUND: Sjogren syndrome is a chronic autoimmune disorder of the exocrine
      glands associated with cardiovascular events. We aimed to evaluate postoperative
      complications in patients with Sjogren syndrome undergoing noncardiac surgery.
      Specifically, we tested the primary hypothesis that patients with Sjogren
      syndrome have a greater risk of postoperative cardiovascular complications than
      those without the disease. Our secondary hypotheses were that patients with
      Sjogren syndrome are at greater risk of thromboembolic complications,
      microcirculatory complications, and mortality. METHODS: We obtained censuses of
      2009 to 2010 inpatient hospital discharges across 7 states. Sjogren syndrome was
      identified by the present-on-admission diagnosis code 710.2. Each Sjogren n
      syndrome discharge was propensity matched to 4 control discharges. A generalized
      linear model was used to compare matched Sjogren syndrome patients and controls
      on risk of in-hospital cardiovascular complications, thromboembolic
      complications, microcirculatory complications, and mortality. RESULTS: Among 5.5
      million qualifying discharges, our final matched sample contained 22,785 matched
      discharges, including 4557 with Sjogren syndrome. Sixty-six (1.45%) of the
      matched discharges with Sjogren syndrome and 213 (1.17%) of the matched controls
      had associated in-hospital cardiovascular complications. The adjusted odds ratio
      (99% confidence interval) was estimated at 1.14 (0.79-1.64), which was not
      statistically significant (P = 0.35). There were no significant differences in
      the odds of in-hospital thromboembolic complications (1.12 [0.82-1.53]; P =
      0.36), in the odds of in-hospital microcirculatory complications (0.98 [0.77
      1.26]; P = 0.86), or in the odds of in-hospital mortality (1.11 [0.76-1.61]; P =
      0.49). CONCLUSIONS: The presence of Sjogren syndrome does not place patients at
      an increased risk for postoperative complications or in-hospital mortality.

PMID- 26309020
TI  - The need for cost-effective choices to treat patients with bipolar 1 disorders
      including asenapine.
AB  - BACKGROUND: Bipolar 1 disorders (BPD) are a chronic disorder with prevalence
      rates of up to 2.6% of the adult population or higher and appreciable direct and
      indirect costs. As a result, these are a concern to health authorities especially
      given the low age of onset. Consequently, there is a need to treat BPD patients
      well and improve their quality-of-life. Pharmacotherapy includes mood stabilizers
      and atypical antipsychotics (AAPs). AAPs have different mechanisms of action and
      side-effects, so treatment needs to be tailored. Asenapine in clinical trials is
      as effective as olanzapine, with less metabolic side-effects. METHODS: Chitnis
      and colleagues assessed the cost-effectiveness of asenapine among patients in
      healthcare databases. RESULTS AND CONCLUSION: They showed in routine care that
      asenapine also reduces hospital and emergency room admissions, making it cost
      neutral in BPD, which is of interest to health authorities and clinicians.

PMID- 26309021
TI  - Vascular risk factors aggravate the progression of Parkinson's disease: a five
      year follow-up study in Chinese patients.
AB  - OBJECTIVE: Some studies have found that vascular risk factors were related to an
      increased risk of Parkinson's disease. In order to investigate the comorbidities
      of the vascular risk factors with PD and their impact on PD progression, we
      launched a five-year follow-up study in 247 outpatients with probable PD.
      METHODS: The incidence of vascular risk factors including hypertension, diabetes,
      hypercholesterolemia, hyperhomocysteinemia and carotid atherosclerotic plaque
      analyzed. The Hoen and Yahr score with and without vascular risk factors were
      compared at initial and at final evaluation. RESULTS: Multiple regression
      analysis showed that age, hypertension and hyperhomocysteinemia were significant
      variables that are associated with the Hoen and Yahr scales. Younger patients
      with hypertension or hyperhomocysteinemia showed a greater increasing in the Hoen
      and Yahr score. There were no significant correlations among the Hoen and Yahr
      score with sex, initial of the Hoen and Yahr score, diabetes,
      hypercholesterolemia or carotid atherosclerotic plaque. CONCLUSION: The vascular
      risk factors are common comorbidities of PD. Younger, more educated patients are
      more likely to have quicker dyskinesia decline. In addition, hypertension and
      hyperhomocysteinemia may aggravate the progression of PD. The prevention and
      treatment of hypertension and hyperhomocysteinemia are important for PD patients.

PMID- 26309022
TI  - A Fluorescent Probe to Measure DNA Damage and Repair.
AB  - DNA damage and repair is a fundamental process that plays an important role in
      cancer treatment. Base excision repair (BER) is a major repair pathway that often
      leads to drug resistance in DNA-targeted cancer chemotherapy. In order to measure
      BER, we have developed a near infrared (NIR) fluorescent probe. This probe binds
      to a key intermediate, termed apurinic/apyrimidinic (AP) site, in the BER pathway
      where DNA damage and repair occurs. We have developed an assay to show the
      efficacy of the probe binding to AP sites and have shown that it can distinguish
      AP sites in DNA extract from chemotherapy treated cells. This probe has potential
      application in monitoring patient response to chemotherapy and evaluating new
      drugs in development. 

PMID- 26309023
TI  - Effectiveness of Provider and Community Interventions to Improve Treatment of
      Uncomplicated Malaria in Nigeria: A Cluster Randomized Controlled Trial.
AB  - The World Health Organization recommends that malaria be confirmed by
      parasitological diagnosis before treatment using Artemisinin-based Combination
      Therapy (ACT). Despite this, many health workers in malaria endemic countries
      continue to diagnose malaria based on symptoms alone. This study evaluates
      interventions to help bridge this gap between guidelines and provider practice. A
      stratified cluster-randomized trial in 42 communities in Enugu state compared 3
      scenarios: Rapid Diagnostic Tests (RDTs) with basic instruction (control); RDTs
      with provider training (provider arm); and RDTs with provider training plus a
      school-based community intervention (provider-school arm). The primary outcome
      was the proportion of patients treated according to guidelines, a composite
      indicator requiring patients to be tested for malaria and given treatment
      consistent with the test result. The primary outcome was evaluated among 4946
      (93%) of the 5311 patients invited to participate. A total of 40 communities (12
      in control, 14 per intervention arm) were included in the analysis. There was no
      evidence of differences between the three arms in terms of our composite
      indicator (p = 0.36): stratified risk difference was 14% (95% CI -8.3%, 35.8%; p
      = 0.26) in the provider arm and 1% (95% CI -21.1%, 22.9%; p = 0.19) in the
      provider-school arm, compared with control. The level of testing was low across
      all arms (34% in control; 48% provider arm; 37% provider-school arm; p = 0.47).
      Presumptive treatment of uncomplicated malaria remains an ingrained behaviour
      that is difficult to change. With or without extensive supporting interventions,
      levels of testing in this study remained critically low. Governments and
      researchers must continue to explore alternative ways of encouraging providers to
      deliver appropriate treatment and avoid the misuse of valuable medicines. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01350752.

PMID- 26309025
TI  - Contact Lens Applications and the Corneal Dystrophies: A Review.
AB  - The cornea is precious to sight. Its intricate cellular arrangement and
      physiology enable it to be transparent and refractive. Corneal dystrophies (CDs)
      impact vision at various decades of life depending on the dystrophy at hand. Left
      untreated, visual ramifications ensue. This review article will summarize the
      current knowledge of the various CDs and the relatively controversial
      classification based on new genetic knowledge and clinical and histological
      characteristics. The application of contact lenses, both soft and rigid, has a
      place in the care and rehabilitation of these unique corneas. 

PMID- 26309024
TI  - Epithelial Sodium Channel-Mediated Sodium Transport Is Not Dependent on the
      Membrane-Bound Serine Protease CAP2/Tmprss4.
AB  - The membrane-bound serine protease CAP2/Tmprss4 has been previously identified in
      vitro as a positive regulator of the epithelial sodium channel (ENaC). To study
      its in vivo implication in ENaC-mediated sodium absorption, we generated a
      knockout mouse model for CAP2/Tmprss4. Mice deficient in CAP2/Tmprss4 were
      viable, fertile, and did not show any obvious histological abnormalities.
      Unexpectedly, when challenged with sodium-deficient diet, these mice did not
      develop any impairment in renal sodium handling as evidenced by normal plasma and
      urinary sodium and potassium electrolytes, as well as normal aldosterone levels.
      Despite minor alterations in ENaC mRNA expression, we found no evidence for
      altered proteolytic cleavage of ENaC subunits. In consequence, ENaC activity, as
      monitored by the amiloride-sensitive rectal potential difference (DeltaPD), was
      not altered even under dietary sodium restriction. In summary, ENaC-mediated
      sodium balance is not affected by lack of CAP2/Tmprss4 expression and thus, does
      not seem to directly control ENaC expression and activity in vivo. 

PMID- 26309026
TI  - Changes in Tear Cytokine Concentrations Following Discontinuation of Soft Contact
      Lenses-A Pilot Study.
AB  - PURPOSE: This study investigated changes in selected tear cytokine concentrations
      (IL-1beta, IL-1Ra, IL-6, IL-10, IL-12 (p70), and TNF-alpha) after a 1-week
      washout from soft contact lens wear (CLW), and the repeatability of cytokine
      measurements using custom multiplex assays. METHODS: A total of 10 subjects
      completed this 6-visit (immediately following contact lens removal, and after 1,
      2, 3, 4, and 7 [+/-1] days without CLW) pilot study. Approximately 20 to 30 MUL
      of pooled basal tears were collected from both eyes at each visit. Two custom
      multiplex assays were used by two operators to quantify the concentration of tear
      cytokines. Tear samples from subjects 1 to 6 were analyzed using the first kit by
      operator 1. Tear samples from subject 7 to 10 plus additional tear samples from
      subjects 1 to 5, which were used to determine the between-kit per operator
      repeatability, were analyzed using the second kit by operator 2. Linear mixed
      models were used to determine changes in tear cytokine concentrations over time.
      Between-kit per operator and within-kit per operator repeatabilities were
      assessed using the Bland and Altman analysis. RESULTS: There were no significant
      changes in tear cytokine concentrations over a 1-week washout of CLW. More than
      99% of the tear samples had detectable levels of cytokines using custom multiplex
      assays. Within-kit per operator repeatability was good, but between-kit per
      operator repeatability was poor; likely due to protein degradation, differences
      in operator experience, and operating procedures. CONCLUSION: A washout period
      may not be necessary when evaluating changes in tear cytokines with new contact
      lenses or lens care products. A well-trained operator using standardized
      operating procedures can produce repeatable measurements using custom multiplex
      assays.

PMID- 26309027
TI  - Attenuated Airway Epithelial Cell Interleukin-22R1 Expression in the Infant
      Nonhuman Primate Lung.
AB  - Respiratory tract infections are a leading cause of morbidity and mortality in
      children under 5 years of age. Increased susceptibility to infection is
      associated with deficiencies in immunity during early childhood. Airway
      epithelium represents the first line of mucosal defense against inhaled
      pathogens. However, little is known about epithelial immune mechanisms in the
      maturing lung. IL-22 and its receptor IL-22R1 are important in host defense and
      repair of epithelial barriers. The objective of this study was to determine
      whether a quantitative difference in IL-22R1 exists between infant and adult
      airways using the rhesus macaque monkey as a model of childhood lung development.
      Immunofluorescence staining of tracheal tissue revealed minimal expression of IL
      22R1 in epithelium at 1 month of age, with a progressive increase in fluorescence
      positive basal cells through 1 year of age. Western blot analysis of tracheal
      lysates confirmed significant age-dependent differences in IL-22R1 protein
      content. Further, primary tracheobronchial epithelial cell cultures established
      from infant and adult monkeys showed differential IL-22R1 mRNA and protein
      expression in vitro. To begin to assess the regulation of age-dependent IL-22R1
      expression in airway epithelium, the effect of histone deacetylase and DNA
      methyltransferase inhibitors was evaluated. IL-22R1 mRNA in adult cultures was
      not altered by 5-aza-2'-deoxycytidine or trichostatin A. IL-22R1 mRNA in infant
      cultures showed no change with 5-aza-2'-deoxycytidine but was significantly
      increased after trichostatin A treatment; however, IL-22R1 protein did not
      increase concurrently. These data suggest that IL-22R1 in airway epithelium is
      regulated, in part, by epigenetic mechanisms that are dependent on chronologic
      age. 

PMID- 26309028
TI  - The Effect of Climate Variability on Gray Whales (Eschrichtius robustus) within
      Their Wintering Areas.
AB  - The environmental conditions of the breeding and feeding grounds of the gray
      whale (Eschrichtius robustus) fluctuates at inter-annual scales in response to
      regional and basin climate patterns. Thus, the goals of this study were to assess
      if there are any relationships between summer sea ice on their feeding ground and
      counts of gray whale mother-calf (MC) pairs at Ojo de Liebre Lagoon (OLL); and if
      El Nino Southern Oscillation (ENSO) influences the winter distribution of gray
      whales MC pairs in the three primary breeding lagoons of OLL, San Ignacio Lagoon
      (SIL) and Santo Domingo Channel north of Bahia Magdalena (SDCh). Maximum February
      counts of MC pairs were compared with the length of the open-water season at the
      Bering Sea during the previous year. Then, an ENSO index and sea surface
      temperature anomalies outside the primary lagoons was compared with the maximum
      February counts of MC pairs at these lagoons. Results showed that maximum counts
      of MC pairs in OLL correlates with sea ice conditions in their feeding grounds
      from the previous feeding season, and this relationship can be attributed to
      changes in nutritive condition of females. ENSO-related variability influences
      distribution of MC pairs in the southern area of SDCh during the warm 1998 El
      Nino and cold 1999 La Nina. This supports the hypothesis that changes in the
      whales' distribution related to sea temperature occurs to reduce thermal-stress
      and optimize energy utilization for newborn whales. Although this last conclusion
      should be considered in view of the limited data available from all the whales'
      wintering locations in all the years considered. 

PMID- 26309030
TI  - Individual 5-Fluorouracil Dose Adjustment via Pharmacokinetic Monitoring Versus
      Conventional Body-Area-Surface Method: A Meta-Analysis.
AB  - BACKGROUND: Recent studies suggest that 5-fluorouracil (5-FU) dosing by use of
      pharmacokinetic (PK) parameters is superior to the traditional body surface area
      (BSA) method in colorectal cancer therapy. The purpose of this study was to
      compare the estimated efficacy and toxicity of the use of PK-guided versus BSA
      based dose adjustment of 5-FU in advanced cancers. METHODS: The authors searched
      from electronic databases (up to September, 2014) and abstracts presented at the
      American Society of Clinical Oncology held between 2000 and 2014 for studies
      comparing the response rate and toxicity in 5-FU-based chemotherapy. RESULTS:
      Five eligible articles with 654 patients were included in double-arms and
      contained colorectal cancer, and head and neck cancer. PK-monitored 5-FU therapy
      was associated with significant improvement in overall response rate (odds ratio
      = 2.04, 95% confidence interval, 1.41-2.95, Z = 3.78, P = 0.0002) compared with
      the traditional BSA method. There was no evidence of improved tolerability: grade
      3 to 4 diarrhea, neutropenia, and hand-foot syndrome were found not to be
      significantly different except that mucositis was less prominent for PK-monitored
      5-FU therapy (odds ratio = 0.16, 95% confidence interval, 0.04-0.63, Z = 2.62, P
      = 0.009). CONCLUSIONS: In comparison with conventional BSA method, PK-based 5-FU
      dosage confirmed a superior overall response rate and improved toxicities
      irrespective of significant difference, the results of which indicated that PK-
      monitored 5-FU dosage has the potential to be performed in colorectal cancer
      personalized therapy. More high-quality and multicenter randomized controlled
      trails should be carried out to provide more information for comparing the
      response and toxicity of these 2 dose adjustment methods.

PMID- 26309029
TI  - The Alpha-Melanocyte-Stimulating Hormone Suppresses TLR2-Mediated Functional
      Responses through IRAK-M in Normal Human Keratinocytes.
AB  - Alpha-melanocyte stimulating hormone (alpha-MSH) is a highly conserved 13-aa
      neuropeptide derived from pro-opiomelanocortin by post-translational processing,
      which has been reported to exhibit potent anti-inflammatory activity and a wide
      range of immunosuppressive activities in the skin. However, the regulatory effect
      of alpha-MSH is not completely clear in cutaneous innate immunity. In this study,
      we investigate the functional regulation of alpha-MSH in TLR2-mediated
      inflammatory responses in normal human keratinocytes (HKs). alpha-MSH
      pretreatment down-regulated the Staphylococcus aureus LTA-induced expression of
      both TLR2 and IL-8 as well as NF-kappaB nuclear translocation in HK cells. The
      inhibitory effect of alpha-MSH was blocked by agouti signaling protein (ASP), an
      alpha-MSH receptor-1 antagonist. To investigate the mechanism of this response in
      more detail, siRNA of IRAK-M, a negative regulator of TLR signaling, was utilized
      in these studies. The alpha-MSH suppressive effect on IL-8 production and NF
      kappaB transactivation was inhibited by IRAK-M siRNA transfection in HK cells.
      These results indicate that alpha-MSH is capable of suppressing keratinocyte TLR2
      mediated inflammatory responses induced by S. aureus-LTA, thus demonstrating
      another novel immunomodulatory activity of alpha-MSH in normal human
      keratinocytes. 

PMID- 26309031
TI  - Can Perhexiline Be Utilized Without Long-Term Toxicity? A Clinical Practice
      Audit.
AB  - BACKGROUND: Perhexiline, originally used as a first-line prophylactic antianginal
      agent, is now regarded primarily as a treatment for otherwise refractory
      myocardial ischemia. Recent studies have also demonstrated its short-term utility
      in heart failure, hypertrophic cardiomyopathy, and inoperable aortic stenosis.
      Its benefits on myocardial energetics state are potentially counter-balanced by
      risk of hepatotoxicity and peripheral neuropathy during long-term treatment if
      drug accumulation occurs. Since perhexiline exhibits complex pharmacokinetics
      with wide inter-individual variability, its long-term use requires regular plasma
      concentration monitoring. In this study, the risk of neuro- and hepato-toxicity
      during long-term perhexiline therapy in relation to the intensity of therapeutic
      drug monitoring was investigated. Furthermore, determinants of mortality during
      perhexiline treatment were evaluated. METHODS: In 170 patients treated with
      perhexiline for a median of 50 months (interquartile range: 31-94 months),
      outcomes and relationship to plasma drug concentrations were documented. RESULTS:
      Rationale for treatment with perhexiline included myocardial ischemia in 88% and
      severe systolic heart failure in 38%. Plasma concentrations were within the
      therapeutic range of 150-600 ng/mL on 65% of assay occasions and toxic levels
      accounted for 8.8% of measurements. No patient developed hepatotoxicity
      attributable to perhexiline while 3 developed peripheral neuropathy possibly
      induced by treatment. Actuarial 5-year survival rate was 83% overall, and 76.3%
      in patients with associated systolic heart failure. CONCLUSIONS: This first audit
      of a large population treated long-term perhexiline demonstrates the following:
      (1) Although the frequency of monitoring is less than ideal, therapeutic drug
      monitoring effectively limits occurrence of toxic drug concentrations and
      virtually eliminates long-term hepato- and neuro-toxicity and (2) Mortality rates
      during long-term therapy, notably for patients with concomitant heart failure,
      are surprisingly low.

PMID- 26309032
TI  - Identification of a Cryptic Bacterial Promoter in Mouse (mdr1a) P-Glycoprotein
      cDNA.
AB  - The efflux transporter P-glycoprotein (P-gp) is an important mediator of various
      pharmacokinetic parameters, being expressed at numerous physiological barriers
      and also in multidrug-resistant cancer cells. Molecular cloning of homologous
      cDNAs is an important tool for the characterization of functional differences in
      P-gp between species. However, plasmids containing mouse mdr1a cDNA display
      significant genetic instability during cloning in bacteria, indicating that mdr1a
      cDNA may be somehow toxic to bacteria, allowing only clones containing mutations
      that abrogate this toxicity to survive transformation. We demonstrate here the
      presence of a cryptic promoter in mouse mdr1a cDNA that causes mouse P-gp
      expression in bacteria. This expression may account for the observed toxicity of
      mdr1a DNA to bacteria. Sigma 70 binding site analysis and GFP reporter plasmids
      were used to identify sequences in the first 321 bps of mdr1a cDNA capable of
      initiating bacterial protein expression. An mdr1a M107L cDNA containing a single
      residue mutation at the proposed translational start site was shown to allow sub
      cloning of mdr1a in E. coli while retaining transport properties similar to wild
      type P-gp. This mutant mdr1a cDNA may prove useful for efficient cloning of mdr1a
      in E. coli. 

PMID- 26309034
TI  - Characterization of Rhinitis According to the Asthma Status in Adults Using an
      Unsupervised Approach in the EGEA Study.
AB  - BACKGROUND: The classification of rhinitis in adults is missing in
      epidemiological studies. OBJECTIVE: To identify phenotypes of adult rhinitis
      using an unsupervised approach (data-driven) compared with a classical hypothesis
      driven approach. METHODS: 983 adults of the French Epidemiological Study on the
      Genetics and Environment of Asthma (EGEA) were studied. Self-reported symptoms
      related to rhinitis such as nasal symptoms, hay fever, sinusitis, conjunctivitis,
      and sensitivities to different triggers (dust, animals, hay/flowers, cold air...)
      were used. Allergic sensitization was defined by at least one positive skin prick
      test to 12 aeroallergens. Mixture model was used to cluster participants,
      independently in those without (Asthma-, n = 582) and with asthma (Asthma+, n =
      401). RESULTS: Three clusters were identified in both groups: 1) Cluster A (55%
      in Asthma-, and 22% in Asthma+) mainly characterized by the absence of nasal
      symptoms, 2) Cluster B (23% in Asthma-, 36% in Asthma+) mainly characterized by
      nasal symptoms all over the year, sinusitis and a low prevalence of positive skin
      prick tests, and 3) Cluster C (22% in Asthma-, 42% in Asthma+) mainly
      characterized by a peak of nasal symptoms during spring, a high prevalence of
      positive skin prick tests and a high report of hay fever, allergic rhinitis and
      conjunctivitis. The highest rate of polysensitization (80%) was found in
      participants with comorbid asthma and allergic rhinitis. CONCLUSION: This cluster
      analysis highlighted three clusters of rhinitis with similar characteristics than
      those known by clinicians but differing according to allergic sensitization, and
      this whatever the asthma status. These clusters could be easily rebuilt using a
      small number of variables.

PMID- 26309035
TI  - Research highlights: microfluidically-fabricated materials.
AB  - Polymer particles with precise shapes or chemistries are finding unique uses in a
      variety of applications, including tissue engineering, drug delivery, barcoding,
      and diagnostic imaging. Microfluidic systems have been and are continuing to play
      a large role in enabling the precision synthesis of designer particles in a
      uniform manner. To expand the impact of these microfluidic-fabricated materials
      additional fundamental capabilities should still be developed. The capability to
      fabricate microparticles with complex three-dimensional shapes and increase the
      production rate of particles to an industrial scale will allow evaluation of
      shaped particles in a range of new applications to enhance biological, magnetic,
      optical, surface wetting, as well as other interfacial or mechanical properties
      of materials. Here we highlight work applying large collections of simple
      spherical microgels, with unique surface chemistry that allows in situ particle
      particle annealing, to form microporous injectable scaffolds for accelerated
      tissue regeneration. We also report on two other techniques that are addressing
      the ability to create 3D-shaped microparticles by first sculpting a fluid
      precursor stream, and increasing the rate of production of particles using
      contact lithography to millions of particles per hour. The combination of these
      capabilities and the applications they will enable suggest a bright future for
      microfluidics in making the next materials. 

PMID- 26309036
TI  - Investigations into the binding of jadomycin DS to human topoisomerase IIbeta by
      WaterLOGSY NMR spectroscopy.
AB  - The jadomycins are a family of secondary metabolites produced by S. venezuelae
      ISP5230. Specific jadomycins have been shown to possess a variety of anticancer,
      antifungal, and antibacterial properties, with different molecular mechanisms of
      action. Herein we demonstrate qualitative and quantitative direct binding between
      the validated anticancer target human topoisomerase IIbeta and jadomycin DS using
      WaterLOGSY NMR spectroscopy. Additionally, we report for the first time, that
      jadomycin DS also binds a variety of other proteins, likely in a non-specific
      manner. Such interactions may rationalize the potential polypharmacology of
      jadomycin DS. 

PMID- 26309038
TI  - A Ni(OH)2-modified Ti-doped alpha-Fe2O3 photoanode for improved
      photoelectrochemical oxidation of urea: the role of Ni(OH)2 as a cocatalyst.
AB  - For semiconductor-based PEC systems, loading an appropriate cocatalyst on a
      semiconductor (such as a solar-active material) can significantly improve the PEC
      activity due to the suppression of photogenerated charge recombination. But there
      is little direct information about the role of a cocatalyst in the spatial
      separation of photogenerated charge carriers. In our work, a combination of
      surface photovoltage spectroscopy (SPS), transient photovoltage (TPV) technique,
      photoelectrochemical impedance spectroscopy (PEIS) and transient photocurrent
      measurements was used to study the real role of Ni(OH)2 as a cocatalyst for the
      enhanced PEC performance of Ni(OH)2-modified Ti-doped alpha-Fe2O3. It was found
      that Ni(OH)2 as a hole storage layer enhances the separation of photogenerated
      charge carriers and increases the lifetime of holes, which contributed to the
      enhanced photocurrent. In addition, Ni(OH)2 is a good cocatalyst for urea
      oxidation which suppresses the over-potential, resulting in a negative shift of
      the onset potential. 

PMID- 26309037
TI  - Bone Mineral Density as a Marker of Cumulative Estrogen Exposure in Psychotic
      Disorder: A 3 Year Follow-Up Study.
AB  - Altered estrogen-induced neuroprotection has been implicated in the etiology of
      psychotic disorders. Using bone mineral density as a marker of lifetime estrogen
      exposure, a longitudinal family study was conducted to discriminate between
      etiological mechanisms and secondary effects of disease and treatment. Dual X-ray
      absorptiometry scans were acquired twice, with an interval of 3 years, in 30
      patients with psychotic disorder (male (M)/female (F): 24/6, mean age of 32 years
      at second measurement), 44 non-psychotic siblings of patients with a psychotic
      disorder (M/F: 26/18, mean age 32) and 27 controls (M/F: 7/20, mean age 35).
      Total bone mineral density, Z-scores and T-scores were measured in the lumbar
      spine and proximal femur. Associations between group and bone mineral density
      changes were investigated with multilevel random regression analyses. The effect
      of prolactin-raising antipsychotic medication was evaluated. (Increased risk of)
      psychotic disorder was not associated with disproportionate bone mineral density
      loss over a three year period. Instead, femoral bone mineral density measures
      appeared to decrease less in the patient versus control comparison (total BMD: B
      = 0.026, 95% CI 0.002 to 0.050, p = 0.037; Z-score: B = 0.224, 95% CI 0.035 to
      0.412, p = 0.020; and T-score: B = 0.193, 95% CI 0.003 to 0.382, p = 0.046).
      Current or past use of a prolactin-raising antipsychotic medication was not
      associated with bone mineral density changes. In this small longitudinal study,
      there was no evidence of ongoing estrogen deficiency in psychotic disorder as
      there was no excessive loss of bone mineral density over a 3-year period in
      patients using antipsychotic medication. 

PMID- 26309039
TI  - LytB1 and LytB2 of Mycobacterium tuberculosis Are Not Genetically Redundant.
AB  - Mycobacterium tuberculosis synthesises isoprenoid precursors via the MEP/DOXP
      pathway and at least five enzymes in the pathway (Dxs1, Dxr/IspC, IspD, IspF, and
      GcpE/IspG) are required for growth in vitro. We investigated the role of LytB
      (IspH) in M. tuberculosis; M. tuberculosis is unusual in that it has two homologs
      LytB1 and LytB2. We were unable to delete the lytB2 gene unless we provided an
      additional copy elsewhere, demonstrating that this is the essential homolog. We
      expressed lytB1 from the lytB2 promoter and confirmed that this could not
      complement for loss of function of lytB2, despite LytB1 possessing all the
      previously described conserved critical residues. Interestingly the sole LytB
      homolog of Mycobacterium smegmatis was able to compensate for loss of LytB2 in M.
      tuberculosis. We tested translational fusions of LytB1 and LytB2 for
      functionality in M. tuberculosis, but only a fusion with 90% N-terminal LytB2 and
      10% C-terminal LytB1 was functional. In order to identify the key difference
      between the two proteins, site directed mutagenesis was used to change LytB2
      residues into their counterparts in LytB1. None of these amino acid substitutions
      was essential for function and all lytB2 mutant alleles were functional. In
      contrast, mutation of the key residues for [Fe4S4] cluster formation, as well as
      a catalytic residue in LytB1 did not result in functional complementation. Thus,
      although LytB1 and LytB2 are not genetically redundant, this is not dependent on
      small amino acid changes, but is likely to be a result of major overall
      structural differences. 

PMID- 26309040
TI  - Organic Farming: Biodiversity Impacts Can Depend on Dispersal Characteristics and
      Landscape Context.
AB  - Organic farming, a low intensity system, may offer benefits for a range of taxa,
      but what affects the extent of those benefits is imperfectly understood. We
      explored the effects of organic farming and landscape on the activity density and
      species density of spiders and carabid beetles, using a large sample of paired
      organic and conventional farms in the UK. Spider activity density and species
      density were influenced by both farming system and surrounding landscape. Hunting
      spiders, which tend to have lower dispersal capabilities, had higher activity
      density, and more species were captured, on organic compared to conventional
      farms. There was also evidence for an interaction, as the farming system effect
      was particularly marked in the cropped area before harvest and was more
      pronounced in complex landscapes (those with little arable land). There was no
      evidence for any effect of farming system or landscape on web-building spiders
      (which include the linyphiids, many of which have high dispersal capabilities).
      For carabid beetles, the farming system effects were inconsistent. Before
      harvest, higher activity densities were observed in the crops on organic farms
      compared with conventional farms. After harvest, no difference was detected in
      the cropped area, but more carabids were captured on conventional compared to
      organic boundaries. Carabids were more species-dense in complex landscapes, and
      farming system did not affect this. There was little evidence that non-cropped
      habitat differences explained the farming system effects for either spiders or
      carabid beetles. For spiders, the farming system effects in the cropped area were
      probably largely attributable to differences in crop management; reduced inputs
      of pesticides (herbicides and insecticides) and fertilisers are possible
      influences, and there was some evidence for an effect of non-crop plant species
      richness on hunting spider activity density. The benefits of organic farming may
      be greatest for taxa with lower dispersal abilities generally. The evidence for
      interactions among landscape and farming system in their effects on spiders
      highlights the importance of developing strategies for managing farmland at the
      landscape-scale for most effective conservation of biodiversity. 

PMID- 26309041
TI  - Exploring the Links between Post-Industrial Landscape History and Ecology through
      Participatory Methods.
AB  - There is increasing recognition of the importance for local biodiversity of post
      mining sites, many of which lie near communities that have suffered significant
      social and economic deprivation as the result of mine closures. However, no
      studies to date have actively used the knowledge of local communities to relate
      the history and treatment of post-mining sites to their current ecological
      status. We report a study of two post-mining sites in the Yorkshire coalfield of
      the UK in which the local community were involved in developing site histories
      and assessing plant and invertebrate species composition. Site histories
      developed using participatory GIS revealed that the sites had a mixture of areas
      of spontaneous succession and technical reclamation, and identified that both
      planned management interventions and informal activities influenced habitat
      heterogeneity and ecological diversity. Two groups of informal activity were
      identified as being of particular importance. Firstly, there has been active
      protection by the community of flower-rich habitats of conservation value (e.g.
      calcareous grassland) and distinctive plant species (e.g. orchids) which has also
      provided important foraging resources for butterfly and bumblebee species.
      Secondly, disturbance by activities such as use of motorbikes, informal camping,
      and cutting of trees and shrubs for fuel, as well as planned management
      interventions such as spreading of brick rubble, has provided habitat for plant
      species of open waste ground and locally uncommon invertebrate species which
      require patches of bare ground. This study demonstrates the importance of
      informal, and often unrecorded, activities by the local community in providing
      diverse habitats and increased biodiversity within a post-mining site, and shows
      that active engagement with the local community and use of local knowledge can
      enhance ecological interpretation of such sites and provide a stronger basis for
      successful future management. 

PMID- 26309042
TI  - A multimodal approach to ankle instability: Interrelations between subjective and
      objective assessments of ankle status in athletes.
AB  - The aim of this retrospective cohort study is to investigate the association
      between different subjective and objective assessments of ankle function in a
      population of athletes with or without functional ankle instability (FAI). 29
      athletes with a history of ankle spraining were divided into two groups according
      to their ankle status: 16 with FAI (initial ankle sprain with residual functional
      instability) (age 24.6 +/- 3.1 years), and 13 COPERS (initial ankle sprain
      without residual instability) (age 25.3 +/- 4.4 years). The assessment of each
      individual's ankle function was based on three approaches: The "functional-ankle
      ability-measure" (FAAM) assessing subjective ankle functionality, measures of
      sensorimotor control as objective functional measurements and MRI-based T2
      mapping as a quantitative marker of compositional joint status. Pearson's product
      moment-correlation coefficient, student's t-test and analysis-of-variance were
      used for statistical analysis. Significant group differences existed for
      subjective ankle function (FAAM, p = 0.04) and MRI-data mainly in the medial
      compartment of the ankle joint (p <= 0.05). We found unique associations between
      T2-mapping results and sensorimotor scores in the COPER (r = -0.756-0.849), and
      "FAI"-group (r = 0.630-0.657). The location and magnitude differed between
      groups. No correlations existed between these measures and the FAAM. This
      exploratory study provides preliminary evidence for potential interrelations
      between various diagnostic measures of ankle function and structure in
      individuals with and without FAI. We found associations between MRI-results and
      selected measures of sensorimotor control, indicating a potential link between
      loss of ankle function and early joint degeneration. Despite these
      interrelations, each of the different assessment options appears to contain
      unique information on ankle functionality important in a clinical assessment.

PMID- 26309043
TI  - Vaginal mesh products: each an entity unto itself.

PMID- 26309044
TI  - Sunscreen formulations may serve as additional water barrier on skin surface: a
      clinical assessment.
AB  - OBJECTIVES: Extended water exposure can cause stratum corneum swelling and a more
      porous skin barrier. People often wear water-resistant sunscreen formulations
      during extended period of water activities in the summer to protect skin from
      harmful UV rays. We wanted to evaluate whether sunscreen formulations can also
      serve as additional water barriers to help mitigate the disruption in stratum
      corneum caused by constant exposure to water. METHODS: We conducted trans
      epidermal water loss (TEWL) measurement in a controlled water patch (including
      salt and chlorine water) model and then applied this relevant model to study the
      effects of pre-treatments of sunscreen sprays and stick. We also conducted water
      sorption-desorption test in vivo with and without sunscreens. Finally, we studied
      the effect of constant water exposure combined with a known irritant, sodium
      lauryl sulphate (SLS), in a randomized clinical trial. RESULTS: We found that
      application of sunscreen formulations help mitigate water-induced barrier
      disruption by repelling water at skin surface. Pre-treatment of sunscreen also
      statistically decreased the irritation in an acute patch test model. CONCLUSIONS:
      Hydrophobic sunscreen formulations can help protect skin from extended water
      exposure by serving as additional water barriers.

PMID- 26309045
TI  - Size- and morphology-controllable synthesis of MIL-96 (Al) by hydrolysis and
      coordination modulation of dual aluminium source and ligand systems.
AB  - In this paper, an efficient method to fabricate Al-based metal organic framework
      (Al-MOF) MIL-96 crystals with controllable size and morphology, by mixing other
      forms of reactants to replace the coordination modulators or capping agents, is
      presented. The size and morphology of the MIL-96 crystals can be selectively
      varied by simply altering the ratio of dual reactants via their hydrolysis
      reaction. All the samples were characterized by X-ray powder diffraction (XRD),
      scanning electron microscopy (SEM), Fourier Transform Infrared (FT-IR)
      spectroscopy, thermogravimetric analysis (TGA) and nitrogen sorption. Then based
      on the BFDH theory, a mechanism for the impact of hydrolysis of reactants on the
      crystal size and morphology is presented and discussed. We also evaluated the
      performance of these MOFs as sorbents for capturing CO2, and they all show
      enhanced adsorption properties compared with the bulk material, displaying high
      adsorption capacities on CO2 at atmospheric pressure and ambient temperature. 

PMID- 26309046
TI  - Using Satellite Tracking and Isotopic Information to Characterize the Impact of
      South American Sea Lions on Salmonid Aquaculture in Southern Chile.
AB  - Apex marine predators alter their foraging behavior in response to spatial and/or
      seasonal changes in natural prey distribution and abundance. However, few studies
      have identified the impacts of aquaculture that represents a spatially and
      temporally predictable and abundant resource on their foraging behavior. Using
      satellite telemetry and stable isotope analysis we examined the degree of spatial
      overlap between the South American sea lion (SASL) and salmon farms, and quantify
      the amount of native prey versus farmed salmonids in SASL diets. We instrumented
      eight SASL individuals with SRDL-GPS tags. Vibrissae, hair and skin samples were
      collected for delta13C and delta15N analyses from five of the tagged individuals
      and from four males captured in a haul-out located adjacent to salmon farms.
      Tracking results showed that almost all the foraging areas of SASL are within
      close proximity to salmon farms. The most important prey for the individuals
      analyzed was farmed salmonids, with an estimated median (+/-SD) contribution of
      19.7 +/- 13.50/00 and 15.3 +/- 9.60/00 for hair and skin, respectively. Using
      vibrissae as a temporal record of diet for each individual, we observed a
      remarkable switch in diet composition in two SASL, from farmed salmonids to
      pelagic fishes, which coincided with the decrease of salmon production due to the
      infectious salmon anemia virus that affected salmon farms in Chile at the end of
      2008. Our study demonstrates the usefulness of integrating stable isotope derived
      dietary data with movement patterns to characterize the impacts of a non-native
      prey on the foraging ecology of an apex marine predator, providing important
      applied implications in situations where interactions between aquaculture and
      wildlife are common. 

PMID- 26309047
TI  - Optimal Sunshade Configurations for Space-Based Geoengineering near the Sun-Earth
      L1 Point.
AB  - Within the context of anthropogenic climate change, but also considering the
      Earth's natural climate variability, this paper explores the speculative
      possibility of large-scale active control of the Earth's radiative forcing. In
      particular, the paper revisits the concept of deploying a large sunshade or
      occulting disk at a static position near the Sun-Earth L1 Lagrange equilibrium
      point. Among the solar radiation management methods that have been proposed thus
      far, space-based concepts are generally seen as the least timely, albeit also as
      one of the most efficient. Large occulting structures could potentially offset
      all of the global mean temperature increase due to greenhouse gas emissions. This
      paper investigates optimal configurations of orbiting occulting disks that not
      only offset a global temperature increase, but also mitigate regional differences
      such as latitudinal and seasonal difference of monthly mean temperature. A
      globally resolved energy balance model is used to provide insights into the
      coupling between the motion of the occulting disks and the Earth's climate. This
      allows us to revise previous studies, but also, for the first time, to search for
      families of orbits that improve the efficiency of occulting disks at offsetting
      climate change on both global and regional scales. Although natural orbits exist
      near the L1 equilibrium point, their period does not match that required for
      geoengineering purposes, thus forced orbits were designed that require small
      changes to the disk attitude in order to control its motion. Finally,
      configurations of two occulting disks are presented which provide the same
      shading area as previously published studies, but achieve reductions of residual
      latitudinal and seasonal temperature changes. 

PMID- 26309048
TI  - The association between subgingival periodontal pathogens and systemic
      inflammation.
AB  - AIM: To investigate associations between periodontal disease pathogens and levels
      of systemic inflammation measured by C-reactive protein (CRP). METHODS: A
      representative sample of dentate 60-70-year-old men in Northern Ireland had a
      comprehensive periodontal examination. Men taking statins were excluded.
      Subgingival plaque samples were analysed by quantitative real time PCR to
      identify the presence of Aggregatibacter actinomycetemcomitans, Porphyromonas
      gingivalis, Treponema denticola and Tannerella forsythia. High-sensitivity CRP
      (mg/l) was measured from fasting blood samples. Multiple linear regression
      analysis was performed using log-transformed CRP concentration as the dependent
      variable, with the presence of each periodontal pathogen as predictor variables,
      with adjustment for various potential confounders. RESULTS: A total of 518 men
      (mean age 63.6 SD 3.0 years) were included in the analysis. Multiple regression
      analysis showed that body mass index (p < 0.001), current smoking (p < 0.01), the
      detectable presence of P. gingivalis (p < 0.01) and hypertension (p = 0.01), were
      independently associated with an increased CRP. The detectable presence of P.
      gingivalis was associated with a 20% (95% confidence interval 4-35%) increase in
      CRP (mg/l) after adjustment for all other predictor variables. CONCLUSION: In
      these 60-70-year-old dentate men, the presence of P. gingivalis in subgingival
      plaque was significantly associated with a raised level of C-reactive protein.

PMID- 26309049
TI  - Palladium-Catalyzed Oxalyl Amide-Directed gamma-Arylation of Aliphatic Amines.
AB  - A method for palladium-catalyzed oxalyl amide-directed arylation of alpha
      unsubstituted aliphatic amines with aryl iodides has been developed. A wide
      variety of aryl iodides are tolerated in this transformation, affording various
      gamma-arylpropylamine derivatives. Heterocyclic iodides can also be competent
      reagents in this gamma-C(sp(3))-H bonds transformation. 

PMID- 26309050
TI  - Safety of an abbreviated duration of dual antiplatelet therapy (<=6 months)
      following second-generation drug-eluting stents for coronary artery disease: A
      systematic review and meta-analysis of randomized trials.
AB  - BACKGROUND: Dual antiplatelet therapy (DAPT) is recommended for >=12 months
      following coronary drug-eluting stents (DES) to reduce risk of major adverse
      ischemic events. Randomized trials suggest an abbreviated DAPT duration (<=6
      months) is adequately protective. However, these trials are individually
      underpowered to detect differences in rare but serious events such as stent
      thrombosis (ST). OBJECTIVES: We performed a meta-analysis of published randomized
      trials to define the impact of abbreviated DAPT (<=6 months) on death, myocardial
      infarction (MI), stent thrombosis (ST), and bleeding complications compared to
      standard-duration DAPT (>=12 months). METHODS: Seven randomized controlled trials
      comparing abbreviated vs. standard DAPT regimens following DES use were
      identified by two independent investigators. Study characteristics were reviewed
      and clinical endpoint data were abstracted and analyzed in aggregate using fixed
      and random-effects models. RESULTS: The seven trials included 15,874 randomized
      patients. Second-generation DES were used in most patients. Compared to standard
      duration DAPT, abbreviated DAPT was not associated with an increase in mortality
      (OR 0.93; CI: 0.73 to 1.17; P = 0.52), MI (OR 1.14; CI: 0.89 to 1.45; P = 0.30)
      or ST (OR 1.25; CI: 0.81 to 1.93; P = 0.31). Abbreviated DAPT was associated with
      significantly fewer major bleeding complications (OR 0.52; CI: 0.34 to 0.82; P =
      0.005). The results were consistent between fixed and random-effects models, with
      no heterogeneity. Sensitivity analyses adjusting for inclusion of bare metal
      stents, 1st generation DES and/or abbreviated DAPT regimens of 3 months resulted
      in similar conclusions. CONCLUSIONS: In a meta-analysis of >15,000 patients
      primarily treated with second-generation DES, abbreviated-duration DAPT (<=6
      months) was associated with a significant reduction in major bleeding
      complications with no evidence of a significant increase in risk of death, MI or
      ST. Accordingly, abbreviated DAPT should be strongly considered for patients
      receiving second generation DES.

PMID- 26309052
TI  - Incorrect Figure in the Article by Wang et al (Arthritis Rheumatol, January
      2014).

PMID- 26309051
TI  - In vitro models for peripheral nerve regeneration.
AB  - The study of peripheral nerve repair and regeneration is particularly relevant in
      the light of the high clinical incidence of nerve lesions. However, the clinical
      outcome after nerve lesions is often far from satisfactory and the functional
      recovery is almost never complete. Therefore, a number of therapeutic approaches
      are being investigated, ranging from local delivery of trophic factors and other
      molecules to bioactive biomaterials and complex nerve prostheses. Translation of
      the new therapeutic approaches to the patient always requires a final pre
      clinical step using in vivo animal models. The need to limit as much as possible
      animal use in biomedical research, however, makes the preliminary use of in vitro
      models mandatory from an ethical point of view. In this article, the different
      types of in vitro models available today for the study of peripheral nerve
      regeneration have been ranked by adopting a three-step stair model based on their
      increasing ethical impact: (i) cell line-based models, which raise no ethical
      concern; (ii) primary cell-based models, which have low ethical impact as animal
      use, although necessary, is limited; and (iii) organotypic ex vivo-based models,
      which raise moderate ethical concerns as the use of laboratory animals is
      required although with much lower impact on animal wellbeing in comparison to in
      vivo models of peripheral nerve regeneration. This article aims to help
      researchers in selecting the best experimental approach for their scientific
      goals driven by the 'Three Rs' (3Rs) rules (Replacement, Reduction or Refinement
      of animal use in research) for scientific research.

PMID- 26309053
TI  - Misidentified Band in Figure in the Article by Zhang et al (Arthritis Rheumatol,
      March 2015).

PMID- 26309055
TI  - Surveillance of the impact of pneumococcal conjugate vaccines in developing
      countries.
AB  - Infection due to Streptococcus pneumoniae is a leading cause of morbidity and
      mortality in young children, especially in developing countries. With the support
      of Gavi, the Vaccine Alliance, the majority of these countries have introduced
      pneumococcal conjugate vaccines (PCV) into their national immunization programs
      and early data demonstrate a high degree of effectiveness, translating to
      enormous public health benefit through both direct and indirect (herd) effects.
      Future vaccination strategy may be focused on maintaining herd effects rather
      than individual protection. Evaluation of vaccine-type carriage, particularly in
      pneumonia cases, may be an easy, feasible way of measuring continued vaccine
      impact. 

PMID- 26309056
TI  - The emerging functions of regulatory RNA species in skin biology.

PMID- 26309057
TI  - Endoscopic sinus surgery for chronic rhinosinusitis in patients previously
      treated for sinonasal malignancy.
AB  - OBJECTIVES/HYPOTHESIS: Patients with a history of sinonasal malignancy can
      develop chronic rhinosinusitis (CRS) as a consequence of their oncologic
      treatment. Some patients will fail medical management and require endoscopic
      sinus surgery (ESS). This study reviews the use of ESS in the management of CRS
      in patients previously treated for sinonasal malignancy. STUDY DESIGN:
      Retrospective review. METHODS: All patients with a history of sinonasal
      malignancy who developed CRS and underwent ESS were reviewed. Preoperative and
      postoperative imaging and symptoms were collected. Major complications (bleeding,
      orbital injury, and cerebrospinal fluid leak) and minor complications (adhesion
      formation) and postoperative healing were reviewed. RESULTS: Eighteen patients
      were identified. All patients presented with symptoms of CRS and sinonasal
      crusting. Additionally, five patients presented with recurrent facial cellulitis,
      and six patients had mucoceles. No major complications were encountered.
      Postoperatively, all patients reported a subjective improvement in their
      sinonasal symptoms. Comparison of pre- and post-ESS imaging revealed a
      significant improvement in Lund-Mackay scores after ESS (P < 0.001) from 12.8
      (range 5-22) to 7 (range). Despite symptomatic improvement, all patients
      continued to have nasal crusting. All patients who initially presented with
      recurrent facial cellulitis had no further episodes after ESS. None of the
      endoscopically drained mucoceles recurred. CONCLUSION: For patients previously
      treated for sinonasal malignancy with refractory CRS, ESS appears to be a safe
      and effective treatment option. ESS in these patients results in subjective
      improvement in sinonasal symptoms as well as objective improvement in
      radiographic CRS disease burden, although sinonasal crusting will likely not
      resolve. LEVEL OF EVIDENCE: 4.

PMID- 26309058
TI  - Chronic Nonhealing Ulcerated Nodules in a Spanish Boy After Traveling.

PMID- 26309059
TI  - Magnetophoretic Transport Line System for Rapid On-Chip Attomole Protein
      Detection.
AB  - A lab-on-a-chip traveling wave magnetophoresis approach for sensitive and rapid
      protein detection is reported. In this method, a chip-based magnetic microarray
      comprising lines of micrometer-sized thin film magnetic elements was used to
      control the movement of magnetic beads (MBs). The MBs and the chip were
      functionalized, forming a sandwich-type assay. The MBs were transported across a
      detection area, and the presence of target molecules resulted in the
      immobilization of MBs within this area. Target quantification was accomplished by
      MB counting in the detection area using an optical microscope. In order to
      demonstrate the versatility of the microarray, biotinylated antiavidin was
      selected as the target protein. In this case, avidin-functionalized MBs and an
      avidin-functionalized detection area were used. With a total assay time of 1 to
      1.5 h (depending on the labeling approach used), a limit of detection in the
      attomole range was achieved. Compared to on-chip surface plasmon resonance
      biodetection systems, our method has a larger dynamic range and is about a factor
      of 500 times more sensitive. Furthermore, our MB transportation system can
      operate in any chip-based biosensor platform, thereby significantly improving
      traditional biosensors. 

PMID- 26309061
TI  - Probing the Backbone Function of Tumor Targeting Peptides by an Amide-to-Triazole
      Substitution Strategy.
AB  - Novel backbone-modified radiolabeled analogs based on the tumor targeting peptide
      bombesin were synthesized and fully evaluated in vitro and in vivo. We have
      recently introduced the use of 1,4-disubstituted 1,2,3-triazoles as metabolically
      stable trans-amide bond surrogates in radiolabeled peptides in order to improve
      their tumor targeting. As an extension of our approach, we now report several
      backbone-modified analogs of the studied bombesin peptide bearing multiple
      triazole substitutions. We investigated the effect of the modifications on
      several biological parameters including the internalization of the
      radiopeptidomimetics into tumor cells, their affinity toward the gastrin
      releasing peptide receptor (GRPr), metabolic stability in blood plasma, and
      biodistribution in mice bearing GRPr-expressing xenografts. The backbone-modified
      radiotracers exhibited a significantly increased resistance to proteolytic
      degradation. In addition, some of the radiopeptidomimetics retained a nanomolar
      affinity toward GRPr, resulting in an up to 2-fold increased tumor uptake in vivo
      in comparison to a (all amide bond) reference compound. 

PMID- 26309060
TI  - Combined melatonin and exendin-4 therapy preserves renal ultrastructural
      integrity after ischemia-reperfusion injury in the male rat.
AB  - We tested whether combined melatonin (Mel) and exendin-4 (Ex4) treatment can
      better preserve glomerular structural integrity after ischemia-reperfusion (IR)
      injury compared with either alone. Adult male Sprague Dawley rats (n = 50) were
      equally divided into sham control (SC), IR, IR-Ex4 (10 MUg/kg subcutaneously 30
      min after reperfusion and daily for 5 days), IR-Mel (20 mg/kg intraperitoneally
      at 30 min postreperfusion and 50 mg/kg at 6 and 18 hr), and IR-Ex4-Mel were
      euthanized at day 14. Serum creatinine level and urine protein-to-creatinine
      ratio at days 3 and 14 were highest in IR group and lowest in SC, significantly
      higher in IR-Ex4 and IR-Mel groups than in IR-Ex4-Mel group (all P < 0.001)
      without significant difference between IR-Ex4 and IR-Mel groups. Changes in
      podocyte injury score (PIS) and kidney injury score were highest in IR group and
      lowest in SC, significantly higher in IR-Ex4 and IR-Mel groups than in IR-Ex4
      Mel, and significantly higher in IR-Mel group than in IR-Ex4 group (all P <
      0.001). Immunohistochemical microscopic findings of the expressions of FSP-1 and
      WT-1 (two glomerular damage indicators) and KIM-1 and snail (two renal tubular
      damaged indicators) showed an identical pattern, whereas the expressions of ZO-1,
      p-cadherin, podocin, dystroglycan, fibronectin, and synaptopodin (six indices of
      glomerular integrity) demonstrated an opposite pattern compared to that of PIS
      among five groups (all P < 0.001). Protein expressions of inflammatory (TNF
      alpha/NF-kappaB/MMP-9) and oxidative stress (NOX-1, NOX-2, oxidized protein)
      biomarkers exhibited an identical pattern to that of PIS among five groups (all P
      < 0.001). Combined melatonin-exednin-4 therapy further protected glomerulus from
      IR injury.

PMID- 26309062
TI  - Sleep modulates cortical connectivity and excitability in humans: Direct evidence
      from neural activity induced by single-pulse electrical stimulation.
AB  - Sleep-induced changes in human brain connectivity/excitability and their
      physiologic basis remain unclear, especially in the frontal lobe. We investigated
      sleep-induced connectivity and excitability changes in 11 patients who underwent
      chronic implantation of subdural electrodes for epilepsy surgery. Single-pulse
      electrical stimuli were directly injected to a part of the cortices, and cortico
      cortical evoked potentials (CCEPs) and CCEP-related high-gamma activities (HGA:
      100-200 Hz) were recorded from adjacent and remote cortices as proxies of
      effective connectivity and induced neuronal activity, respectively. HGA power
      during the initial CCEP component (N1) correlated with the N1 size itself across
      all states investigated. The degree of cortical connectivity and excitability
      changed during sleep depending on sleep stage, approximately showing dichotomy of
      awake vs. non-rapid eye movement (REM) [NREM] sleep. On the other hand, REM sleep
      partly had properties of both awake and NREM sleep, placing itself in the
      intermediate state between them. Compared with the awake state, single-pulse
      stimulation especially during NREM sleep induced increased connectivity (N1 size)
      and neuronal excitability (HGA increase at N1), which was immediately followed by
      intense inhibition (HGA decrease). The HGA decrease was temporally followed by
      the N2 peak (the second CCEP component), and then by HGA re-increase during sleep
      across all lobes. This HGA rebound or re-increase of neuronal synchrony was
      largest in the frontal lobe compared with the other lobes. These properties of
      sleep-induced changes of the cortex may be related to unconsciousness during
      sleep and frequent nocturnal seizures in frontal lobe epilepsy.

PMID- 26309063
TI  - Evaluating Evidence for Association of Human Bladder Cancer with Drinking-Water
      Chlorination Disinfection By-Products.
AB  - Exposure to chlorination disinfection by-products (CxDBPs) is prevalent in
      populations using chlorination-based methods to disinfect public water supplies.
      Multifaceted research has been directed for decades to identify, characterize,
      and understand the toxicology of these compounds, control and minimize their
      formation, and conduct epidemiologic studies related to exposure. Urinary bladder
      cancer has been the health risk most consistently associated with CxDBPs in
      epidemiologic studies. An international workshop was held to (1) discuss the
      qualitative strengths and limitations that inform the association between bladder
      cancer and CxDBPs in the context of possible causation, (2) identify knowledge
      gaps for this topic in relation to chlorine/chloramine-based disinfection
      practice(s) in the United States, and (3) assess the evidence for informing risk
      management. Epidemiological evidence linking exposures to CxDBPs in drinking
      water to human bladder cancer risk provides insight into causality. However,
      because of imprecise, inaccurate, or incomplete estimation of CxDBPs levels in
      epidemiologic studies, translation from hazard identification directly to risk
      management and regulatory policy for CxDBPs can be challenging. Quantitative risk
      estimates derived from toxicological risk assessment for CxDBPs currently cannot
      be reconciled with those from epidemiologic studies, notwithstanding the
      complexities involved, making regulatory interpretation difficult. Evidence
      presented here has both strengths and limitations that require additional studies
      to resolve and improve the understanding of exposure response relationships.
      Replication of epidemiologic findings in independent populations with further
      elaboration of exposure assessment is needed to strengthen the knowledge base
      needed to better inform effective regulatory approaches. 

PMID- 26309065
TI  - Is Octavalent Pu(VIII) Possible? Mapping the Plutonium Oxyfluoride Series
      PuO(n)F(8-2n) (n = 0-4).
AB  - While the oxidation state Pu(VIII) is shown to be less stable than Pu(V) in the
      PuO4 molecule, it is not clear if the more electronegative fluorine can help to
      stabilize Pu(VIII). Our calculations on PuO(n)F(8-2n) (n = 0-4) molecules notably
      confirm that PuO2F4 has both (1)D(4h) and (5)C(2v) minima with the oxidation
      states Pu(VIII) and Pu(V), respectively, with the latter having lower energy. The
      hybrid-DFT, CCSD(T), and CASSCF methods all give the same result. The results
      conform to a superoxide ligand when n >= 2. PuF8 in a (1)O(h) state can decompose
      to PuF6 and F2, and PuOF6 in a (1)C(2v) state also can break down to PuF6 and 1/2
      O2. The Pu(VIII) anion PuO2F5(-) does have a D(5h) minimum, which also lies above
      a (5)C(2v) Pu(V) peroxide structure. However, the energy differences between the
      different minima are not large, indicating that metastable species with oxidation
      states higher than Pu(V) cannot be completely excluded.

PMID- 26309064
TI  - Potential for enhancing external beam radiotherapy for lung cancer using high-Z
      nanoparticles administered via inhalation.
AB  - Nanoparticle-aided radiation therapy is emerging as a promising modality to
      enhance radiotherapy via the radiosensitizing action of high atomic number (Z)
      nanoparticles. However, the delivery of sufficiently potent concentrations of
      such nanoparticles to the tumor remain a challenge. This study investigates the
      dose enhancement to lung tumors due to high-Z nanoparticles (NPs) administered
      via inhalation during external beam radiotherapy. Here NPs investigated include:
      cisplatin nanoparticles (CNPs), carboplatin nanoparticles (CBNPs), and gold
      nanoparticles (GNPs). Using Monte Carlo-generated megavoltage energy spectra, a
      previously employed analytic method was used to estimate dose enhancement to lung
      tumors due to radiation-induced photoelectrons from the NPs administered via
      inhalation route (IR) in comparison to intravenous (IV) administration. Previous
      studies have indicated about 5% of FDA-approved cisplatin concentrations reach
      the lung via IV. Meanwhile recent experimental studies indicate that 3.5-14.6
      times higher concentrations of NPs can reach the lung by IR compared to IV.
      Taking these into account, the dose enhancement factor (DEF) defined as the ratio
      of the radiotherapy dose with and without nanoparticles was calculated for a
      range of NPs concentrations and tumor sizes. The DEF for IR was then compared
      with that for IV. For IR with 3.5 times higher concentrations than IV, and 2 cm
      diameter tumor, clinically significant DEF values of up to 1.19, 1.26, and 1.51
      were obtained for CNPs, CBNPs and GNPs. In comparison values of 1.06, 1.08, and
      1.15 were obtained via IV administration. For IR with 14.6 times higher
      concentrations, even higher DEF values were obtained e.g. 1.81 for CNPs. Results
      also showed that the DEF increased with increasing field size or decreasing tumor
      volume, as expected. The results of this work indicate that IR administration of
      targeted high-Z CNPs/CBNPs/GNPs could enable clinically significant DEF to lung
      tumors compared to IV administration during external beam radiotherapy. For FDA
      approved concentrations of CNPs or CBNPs considered, this could allow for
      additional dose enhancement to tumors via photoelectric mechanism during
      concomitant chemoradiotherapy.

PMID- 26309066
TI  - Acoustofluidic, label-free separation and simultaneous concentration of rare
      tumor cells from white blood cells.
AB  - Enrichment of rare cells from peripheral blood has emerged as a means to enable
      noninvasive diagnostics and development of personalized drugs, commonly
      associated with a prerequisite to concentrate the enriched rare cell population
      prior to molecular analysis or culture. However, common concentration by
      centrifugation has important limitations when processing low cell numbers. Here,
      we report on an integrated acoustophoresis-based rare cell enrichment system
      combined with integrated concentration. Polystyrene 7 MUm microparticles could be
      separated from 5 MUm particles with a recovery of 99.3 +/- 0.3% at a
      contamination of 0.1 +/- 0.03%, with an overall 25.7 +/- 1.7-fold concentration
      of the recovered 7 MUm particles. At a flow rate of 100 MUL/min, breast cancer
      cells (MCF7) spiked into red blood cell-lysed human blood were separated with an
      efficiency of 91.8 +/- 1.0% with a contamination of 0.6 +/- 0.1% from white blood
      cells with a 23.8 +/- 1.3-fold concentration of cancer cells. The recovery of
      prostate cancer cells (DU145) spiked into whole blood was 84.1 +/- 2.1% with 0.2
      +/- 0.04% contamination of white blood cells with a 9.6 +/- 0.4-fold
      concentration of cancer cells. This simultaneous on-chip separation and
      concentration shows feasibility of future acoustofluidic systems for rapid label
      free enrichment and molecular characterization of circulating tumor cells using
      peripheral venous blood in clinical practice. 

PMID- 26309067
TI  - Computational Study of Pressure-Driven Gas Transport in Nanostructured Carbons:
      An Alternative Approach.
AB  - We demonstrated a computationally efficient method in nonequilibrium molecular
      dynamics (NEMD) simulations to study pressure-driven gas transport in porous
      media. The reflecting particle method (RPM)14 was used to establish a steady
      state gas flow along the transport channel, and the gas density in the feed
      chamber was properly adjusted to allow a constant pressure drop under various
      conditions by using a perturbation-relaxation loop developed here. This method
      was validated for methane flow through carbon nanotubes over a wide range of
      temperatures, giving results comparable to those of the commonly used dual
      control volume grand canonical molecular dynamics (DCV-GCMD) method but at least
      20 times more efficient, even though the transport condition tested is favorable
      for the latter. This made it possible to perform systematic studies on the
      effects of temperature, pressure, and channel size on the transport behaviors.
      Our study shows that adsorption density varies significantly with temperature,
      which dramatically influences the transport mechanisms, especially in small
      channels at low temperatures and under high pressures. This newly developed NEMD
      method can be readily extended to study gas transport through channels with more
      complex surface morphology. 

PMID- 26309069
TI  - Reactive oxygen species and energy machinery: an integrated dynamic model.
AB  - The role of several important reactive oxygen species (ROS) on the Krebs cycle,
      the electron transport chain (ETC) and the two important shuttles has been
      modelled. Major part of the ROS is produced during oxygen reduction in the ETC,
      which has been kinetically simulated, and the changes in the final concentrations
      of several important metabolites were found. The simulation is based on chemical
      kinetics equation, and the associated set of differential equations was solved by
      the ordinary differential equation package in Octave. The validity of the model
      is checked by comparing the experimental results available in the literature with
      the simulations when a part of the ETC is blocked (80%) in the script. The
      present approach is versatile and flexible and has potential applications in
      various simulations. It is easy to study the change in concentrations of various
      metabolites when a particular enzyme or pathway is blocked (say by a drug). The
      Octave script is presented in the text. 

PMID- 26309068
TI  - Accurate Analysis and Evaluation of Acidic Plant Growth Regulators in Transgenic
      and Nontransgenic Edible Oils with Facile Microwave-Assisted Extraction
      Derivatization.
AB  - Determination of plant growth regulators (PGRs) in a signal transduction system
      (STS) is significant for transgenic food safety, but may be challenged by poor
      accuracy and analyte instability. In this work, a microwave-assisted extraction
      derivatization (MAED) method is developed for six acidic PGRs in oil samples,
      allowing an efficient (<1.5 h) and facile (one step) pretreatment. Accuracies are
      greatly improved, particularly for gibberellin A3 (-2.72 to -0.65%) as compared
      with those reported (-22 to -2%). Excellent selectivity and quite low detection
      limits (0.37-1.36 ng mL(-1)) are enabled by fluorescence detection-mass spectrum
      monitoring. Results show the significant differences in acidic PGRs between
      transgenic and nontransgenic oils, particularly 1-naphthaleneacetic acid (1-NAA),
      implying the PGRs induced variations of components and genes. This study
      provides, for the first time, an accurate and efficient determination for labile
      PGRs involved in STS and a promising concept for objectively evaluating the
      safety of transgenic foods. 

PMID- 26309070
TI  - Rhodium Catalyzed Asymmetric Hydrogenation of 2-Pyridine Ketones.
AB  - Catalyzed by [Rh(COD)Binapine]BF4, the asymmetric hydrogenation of 2-pyridine
      ketones has been achieved with excellent enantioselectivities (enantiomeric
      excesses up to 99%) under mild conditions. This method is suitable for various
      kinds of 2-pyridine ketones and their derivatives. A number of enantiomerically
      pure chiral 2-pyridine-aryl/alkyl alcohols were prepared through hydrogenation,
      which can be used directly in organic synthesis. 

PMID- 26309071
TI  - Oncology drug pricing structure is broken.

PMID- 26309072
TI  - Young Children's Comprehension of Temporal Relations in Complex Sentences: The
      Influence of Memory on Performance.
AB  - The present study investigated 3- to 7-year-olds' (N = 91) comprehension of two
      clause sentences containing the temporal connectives before or after. The
      youngest children used an order of mention strategy to interpret the relation
      between clauses: They were more accurate when the presentation order matched the
      chronological order of events: "He ate his lunch, before he played in the garden"
      (chronological) versus "Before he played in the garden, he ate his lunch"
      (reverse). Between 4 and 6 years, performance was influenced by a combination of
      factors that influenced processing load: connective type and presentation order.
      An independent measure of working memory was predictive of performance. The study
      concludes that the memory demands of some sentence structures limits young
      children's comprehension of sentences containing temporal connectives.

PMID- 26309074
TI  - Autophagy restricts HIV-1 infection.

PMID- 26309075
TI  - Nek5: a new regulator of centrosome integrity.

PMID- 26309076
TI  - Lipid transport and epithelial barrier integrity.

PMID- 26309077
TI  - RB in DNA repair.

PMID- 26309078
TI  - Conversion of the CD8 lineage to CD4 T cells.

PMID- 26309079
TI  - Hyperinflammation, T cells, and endotoxemia.

PMID- 26309080
TI  - Progenitor cell fate, SOXC and WNT.

PMID- 26309081
TI  - Casp8p41 and HIV.

PMID- 26309082
TI  - Targeting brain estrogen receptor for binge eating.

PMID- 26309083
TI  - Protection of muscle nuclei.

PMID- 26309084
TI  - ULK1 in type I interferon response.

PMID- 26309085
TI  - Putting the brakes on chondrosarcoma.

PMID- 26309086
TI  - HMGB1 and injury amplification.

PMID- 26309087
TI  - Ciliopathy in PCS (MVA) syndrome.

PMID- 26309088
TI  - ICOS regulates ILC2s in asthma.

PMID- 26309089
TI  - Viral infection at the endothelium.

PMID- 26309090
TI  - Wnt signaling induces epithelial differentiation during cutaneous wound healing.
AB  - Cutaneous wound repair in adult mammals typically does not regenerate original
      dermal architecture. Skin that has undergone repair following injury is not
      identical to intact uninjured skin. This disparity may be caused by differences
      in the mechanisms that regulate postnatal cutaneous wound repair compared to
      embryonic skin development and thus we seek a deeper understanding of the role
      that Wnt signaling plays in the mechanisms of skin repair in both fetal and adult
      wounds. The influence of secreted Wnt signaling proteins in tissue homeostasis
      has galvanized efforts to identify small molecules that target Wnt-mediated
      cellular responses. Wnt signaling is activated by wounding and participates in
      every subsequent stage of the healing process from the control of inflammation
      and programmed cell death, to the mobilization of stem cell reservoirs within the
      wound site. Endogenous Wnt signaling augmentation represents an attractive option
      to aid in the restoration of cutaneous wounds, as the complex mechanisms of the
      Wnt pathway have been increasingly investigated over the years. In this review,
      we summarize recent data elucidating the roles that Wnt signaling plays in
      cutaneous wound healing process. 

PMID- 26309091
TI  - 14th Annual Meeting of the Safety Pharmacology Society: Threading through
      peripheral and central nervous system presentations.
AB  - The 2014 Annual Meeting of the Safety Pharmacology Society discussed
      pathophysiological mechanisms and novel investigational approaches to assess drug
      safety. The plenary keynote reviewed past, present, and future research on
      Alzheimer's disease. Polysomnography tools can uncover drug-induced sleep
      disturbances. FDA examiners currently assess proconvulsive liabilities on a case
      by-case basis due to the lack of official guidance. In contrast, abuse liability
      potential is determined according to established paradigms. The FDA guideline on
      opioid deterrent formulations was discussed. The mechanisms and treatments of
      obstructive sleep apnea (OSA) and diabetes-induced neuropathic pain were
      reviewed. There were salient points arising from the CNS presentations but from a
      pharmacological point of view we note in particular that safety pharmacology
      should move to routinely apply polysomnographic technologies to determine whether
      candidate drugs exert deleterious effects on sleep quality and architecture that
      may markedly decrease quality of life and impair cognitive functions, including
      alertness and reaction time. 

PMID- 26309092
TI  - Lung function changes in mice sensitized to ammonium hexachloroplatinate.
AB  - Occupational exposure to halogenated platinum salts can trigger the development
      of asthma. The risk to the general population that may result from the use of
      platinum in catalytic converters and its emerging use as a diesel fuel additive
      is unclear. To investigate pulmonary responses to platinum, we developed a mouse
      model of platinum hypersensitivity. Mice were sensitized through application of
      ammonium hexachloroplatinate (AHCP) to the shaved back on days 0, 5 and 19, and
      to each ear on days 10, 11 and 12. On days 24 and 29, mice were challenged by
      oropharyngeal aspiration with AHCP in saline. Before and immediately after
      challenge, pulmonary responses were assessed using whole body plethysmography
      (WBP). A dose-dependent increase in immediate responses was observed in AHCP
      sensitized and challenged mice. On days 26 and 31, changes in ventilatory
      responses to methacholine (Mch) aerosol were assessed by WBP; dose-dependent
      increases in Mch responsiveness occurred in sensitized mice. Lymph node cell
      counts indicate a proliferative response in lymph nodes draining the sites of
      application. Bronchoalveolar lavage fluid harvested from sensitized mice
      contained an average of 5% eosinophils compared to less than 0.5% in non
      sensitized mice (p < 0.05); significant increases in total serum immunoglobulin E
      were observed for all sensitized mice. Although a second airway challenge on day
      29 affected some results, only one airway challenge was needed to observe changes
      in lung function. 

PMID- 26309093
TI  - The Potentiation of IFN-gamma and Induction of Cytotoxic Proteins by Pegylated IL
      10 in Human CD8 T Cells.
AB  - Interleukin-10 (IL-10) exerts both immunosuppressive and immunostimulatory
      effects. While the immunosuppressive effects are widely known, it has only been
      recently reported that pegylated recombinant human IL-10 (PEG-rHuIL-10) elicits
      potent interferon-gamma (IFN-gamma) and CD8 T-cell-dependent antitumor effects in
      murine tumor models. In this study, we show that PEG-rHuIL-10 exerts immune
      inhibitory effects on human peripheral blood mononuclear cell (PBMC) bulk
      cultures and stimulatory effects in CD8 T cells within the same culture. Also, in
      isolated CD8 T cells, PEG-rHuIL-10 potentiates prototypic Tc1 cytokine IFN-gamma
      expression and induces perforin and granzyme B secretion. IFN-gamma and granzyme
      B secretion is dependent on T-cell receptor ligation and is therefore not
      indiscriminately released by PEG-rHuIL-10 treatment. STAT3, NF-kappaB, AP1, and
      MEK inhibition blocks IFN-gamma potentiation, while perforin induction is impeded
      by AP1 inhibition, and granzyme B induction is blocked by both AP1 and MEK
      inhibition. These results extend previous pegylated IL-10 preclinical findings to
      human CD8 T cells and implicate a strong degree of translation for pegylated IL
      10 use in cancer therapy. 

PMID- 26309094
TI  - In-utero radiofrequency ablation in fetal piglets: Lessons learned.
AB  - INTRODUCTION: Radiofrequency ablation (RFA) is increasingly utilized in minimally
      invasive fetal intervention. However, the response of different fetal tissues to
      RFA is poorly characterized. We sought to determine the extent of RFA damage in a
      fetal environment. METHODS: 90Day gestation Yorkshire piglets (term 115days) were
      subjected to RFA of the chest and abdominal viscera under various temperatures
      and wattages. The extent of tissue damage was determined by NADPH diaphorase
      histochemistry. RESULTS: Tyne temperature was widely variable and displayed
      varying responses between lung and liver tissue. Tyne exposure to amniotic fluid
      resulted in an increase in amniotic fluid temperature. Collateral damage, even
      across the diaphragm, was readily seen, and ultrasonography did not always
      reflect this injury. CONCLUSIONS: Utilization of extracorporeal tynes heats fluid
      at a greater rate than solid tissue and reliance on temperature sensitive probes
      may result in overheating. The extent of injury may extend beyond damage observed
      by ultrasound examination and varies for different tissues. Additional studies on
      the use of devices that regulate tyne temperature are needed to define optimal
      conditions and better define the extent of adjacent tissue injury.

PMID- 26309096
TI  - Anticoagulation for Extracorporeal Life Support: Direct Thrombin Inhibitors and
      Heparin.
AB  - Since its introduction to bedside clinical practice over 40 years ago,
      extracorporeal life support (ECLS) has been continually changing and improving as
      a life-saving technology. Extracorporeal life support disrupts the normal finely
      maintained balance of coagulation and fibrinolysis by exposing large amounts of
      blood to nonendothelial surfaces. This leads to an inflammatory response with
      activation of the coagulation cascade and the need for systemic anticoagulation.
      Unfractionated heparin (UNFH) is currently the standard anticoagulant in ECLS.
      Alternative anticoagulants have been recently developed with improved safety
      profiles and reliable monitoring. Within this group of agents are the direct
      thrombin inhibitors (DTIs) bivalirudin and argatroban. The purpose of this
      article is to compare these DTIs to the current standard of UNFH anticoagulation
      during ECLS, to evaluate the current literature surrounding the use of these
      drugs in ECLS, and finally to propose therapeutic guidelines for their use in
      ECLS. 

PMID- 26309095
TI  - When Challenging Art Gets Liked: Evidences for a Dual Preference Formation
      Process for Fluent and Non-Fluent Portraits.
AB  - Although fluency theory predominates psychological research on human aesthetics,
      its most severe limitation may be to explain why art that challenges or even
      violates easy processing can nevertheless be aesthetically rewarding. We discuss
      long-standing notions on art's potential to offer mental growth opportunities and
      to tap into a basic epistemic predisposition that hint at a fluency counteracting
      aesthetic pleasure mechanism. Based on divergent strands of literature on
      empirical, evolutionary, and philosophical aesthetics, as well as research on
      disfluency, we presumed that challenging art requires deliberate reflexive
      processing at the level of "aboutness" in order to be experientially pleasing.
      Here, we probed such a cognitive mastering mechanism, achieved by iterative
      cycles of elaboration, as predicted by our model of aesthetic experiences. For
      the study, two kinds of portraits were applied, one associable to a high fluency
      and one to a high stimulation potential (according to results of an extensive
      rating study). In Experiment 1, we provided a repeated evaluation task, which
      revealed a distinctive preference effect for challenging portraits that was
      absent in the visual exposition conditions of a familiarity and a mere exposure
      task (Experiment 2). In a follow-up task (Experiment 3) this preference effect
      was observed with a novel and more encompassing pool of portraits, which
      corroborated its stability and robustness. In an explorative stimulus-transfer
      task (Experiment 4), we investigated the presumed underlying mechanism by testing
      whether the observed effect would generalize onto novel portraits of the same
      artist-specific styles. Results discounted an alternative interpretation of a
      perceptual adaptation effect and hinted at meaning-driven mental activity.
      Conjointly, findings for inexperienced viewers were indicative of an elaboration
      based mastering mechanism that selectively operated for mentally challenging
      portraits. Moreover, findings were in line with a dual-process view of human
      preference formation with art. Theoretical implications and boundary conditions
      are discussed. 

PMID- 26309097
TI  - Assessing Anticoagulation Practice Patterns in Patients on Durable Mechanical
      Circulatory Support Devices: An International Survey.
AB  - Anticoagulation in mechanical circulatory support (MCS) patients dictated by
      local practice, and therefore uniform standards for management are lacking. To
      characterize the worldwide variance in anticoagulation and antiplatelet therapy
      in patients with MCS devices, a 42 item survey was created and distributed
      electronically in August 2014. The survey assessed the center-perceived
      thromboembolic risk (minimal, low, moderate, or high) and characterized the
      antiplatelet and anticoagulant strategies for the Thoratec HeartMate II (HMII)
      and HeartWare HVAD (HVAD). A total of 83/214 centers (39%) responded: North
      America (60/152), Europe (18/50), Australia (2/4), and Asia (3/8). Although the
      most common target international normalized ratio (INR) was 2-3 for both devices,
      significant variability exists. Anticoagulation intensity tended to be lower with
      the HMII, with more centers targeting INR values of less than 2.5. Aspirin
      monotherapy was the most common antiplatelet regimen; however, the HVAD patients
      were more likely to be on daily aspirin doses over 100 mg. In addition,
      parenteral bridging was more frequent with the HVAD device. While 43.8% of
      respondents indicated an increase in the perceived risk of HMII device thrombosis
      in 2014, intensification of anticoagulation (22%) or antiplatelet (11%) therapy
      was infrequent. Our findings verify the wide variety of anticoagulation practice
      patterns between MCS centers.

PMID- 26309098
TI  - Extracorporeal Membrane Oxygenation as a Procedural Rescue Strategy for
      Transcatheter Aortic Valve Replacement Cardiac Complications.
AB  - Cardiovascular complications during or after transcatheter aortic valve
      replacement (TAVR) are associated with extremely high mortality, but
      extracorporeal membrane oxygenation (ECMO) can be used as procedural rescue
      option to improve outcomes when patients experience respiratory or cardiac
      arrest. From 2012 to 2014, 230 patients underwent TAVR and 10 patients (4.3%)
      required emergent venous-arterial ECMO support. Mean age was 83 years, median
      Society of Thoracic Surgeons (STS) score was 15, and mean aortic gradient was 45
      mm Hg. Median left ventricular ejection fraction was 35%. Access for most ECMOs
      was femoral; two patients required central arterial and femoral venous access.
      Extracorporeal membrane oxygenation was initiated in response to hemodynamic
      collapse due to perforation of left ventricle (n = 2), aortic root rupture (n =
      1), moderate-to-severe aortic insufficiency (n = 1), left main impingement (n =
      1), valve embolization (n = 1), severe hypotension and cardiac arrest after
      prolonged rapid pacing sequence (n = 1), ventricular fibrillation (n = 2), and
      ventricular tachycardia (n = 1). Median time of ECMO support was 87 minutes.
      There were three hospital deaths. Post-TAVR mean aortic gradient was 8 mm Hg and
      median hospital stay was 19 days. Additional procedures included valve-in-valve
      placement (n = 1), percutaneous coronary intervention (n = 1), surgical LV repair
      (n = 2), surgical valve replacement (n = 1), aortic root rupture repair, and
      coronary bypass grafting (n = 1). Extracorporeal membrane oxygenation is rescue
      therapy for hemodynamic instable patients who develop TAVR-related cardiac
      complications. 

PMID- 26309099
TI  - Stressful Parental-Bonding Exaggerates the Functional and Emotional Disturbances
      of Primary Dysmenorrhea.
AB  - BACKGROUND: Some evidence suggests that women with primary dysmenorrhea (or
      painful period) often have traumatic experience with parental attachments, but
      the exact relationship is still unclear. PURPOSE: This study aims to investigate
      associations between styles of the parental bonding and the detailed aspects of
      the disorder in Chinese university-student women. METHODS: From university
      student women, we have invited 50 primary dysmenorrhea patients and 111 healthy
      volunteers, to undergo tests of the Functional and Emotional Measure of
      Dysmenorrhea (FEMD), the Family Relationship Questionnaire (FRQ), and the visual
      analogue scale for the pain intensity experienced. RESULTS: Besides the high
      scores of the FEMD Functional and Emotional scales, the dysmenorrhea patients
      also scored significantly higher than the healthy controls on the FRQ scales of
      Paternal Dominance and Maternal Abuse. In patients, the FEMD Emotional scale was
      negatively predicted by the Paternal Freedom Release scale, and the FEMD
      Functional scale was positively predicted by the Maternal Dominance scale.
      CONCLUSIONS: Inappropriate parental bonding or chronic traumatic attachment
      styles have respective relationships with the functional and emotional
      disturbances experienced by the primary dysmenorrhea patients.

PMID- 26309100
TI  - Diosgenin Mitigates Streptozotocin Diabetes-induced Vascular Dysfunction of the
      Rat Aorta: The Involved Mechanisms.
AB  - Chronic diabetes mellitus finally leads to serious vascular dysfunction.
      Diosgenin is a natural steroidal saponin with potential cardiovascular protective
      effect. In this study, the protective effect of diosgenin was checked on the
      aorta from streptozotocin-induced diabetic rats. Diabetic rats received diosgenin
      (40 mg.kg.d) for 7 weeks starting 1 week after intraperitoneal injection of
      streptozotocin (60 mg/kg). Aortic reactivity of endothelium-intact and -denuded
      rings to potassium chloride, phenylephrine, acetylcholine, and isosorbide
      dinitrate were measured and some involved mechanisms were explored. The results
      showed that diosgenin has a hypoglycemic effect and attenuates maximum
      contractile response of endothelium-intact and -denuded rings to PE. In addition,
      endothelium-dependent relaxation to acetylcholine was greater in diosgenin
      treated diabetics with no significant change for endothelium-independent
      relaxation to isosorbide dinitrate and addition of N(G)-nitro-L-arginine methyl
      ester, as a nitric oxide synthase inhibitor eliminated this beneficial effect.
      Furthermore, diosgenin significantly attenuated aortic DNA fragmentation as an
      index of apoptosis and malondialdehyde content, lowered the aortic expression of
      angiotensin converting enzyme and transcription factor nuclear factor-kappaB and
      raised expression of endothelial nitric oxide synthase with no significant effect
      on the activity of superoxide dismutase. Taken together, our study provides
      insight into the mechanisms underlying the beneficial effect of diosgenin as a
      potential therapeutic agent to mitigate vascular dysfunction in diabetes
      mellitus. 

PMID- 26309101
TI  - Dominance in Domestic Dogs: A Quantitative Analysis of Its Behavioural Measures.
AB  - A dominance hierarchy is an important feature of the social organisation of group
      living animals. Although formal and/or agonistic dominance has been found in
      captive wolves and free-ranging dogs, applicability of the dominance concept in
      domestic dogs is highly debated, and quantitative data are scarce. Therefore, we
      investigated 7 body postures and 24 behaviours in a group of domestic dogs for
      their suitability as formal status indicators. The results showed that high
      posture, displayed in most dyadic relationships, and muzzle bite, displayed
      exclusively by the highest ranking dogs, qualified best as formal dominance
      indicators. The best formal submission indicator was body tail wag, covering most
      relationships, and two low postures, covering two-thirds of the relationships. In
      addition, both mouth lick, as included in Schenkel's active submission, and pass
      under head qualified as formal submission indicators but were shown almost
      exclusively towards the highest ranking dogs. Furthermore, a status assessment
      based on changes in posture displays, i.e., lowering of posture (LoP) into half
      low, low, low-on-back or on-back, was the best status indicator for most
      relationships as it showed good coverage (91% of the dyads), a nearly linear
      hierarchy (h' = 0.94, p<0.003) and strong unidirectionality (DCI = 0.97). The
      associated steepness of 0.79 (p<0.0001) indicated a tolerant dominance style for
      this dog group. No significant correlations of rank with age or weight were
      found. Strong co-variation between LoP, high posture, and body tail wag justified
      the use of dominance as an intervening variable. Our results are in line with
      previous findings for captive wolves and free-ranging dogs, for formal dominance
      with strong linearity based on submission but not aggression. They indicate that
      the ethogram for dogs is best redefined by distinguishing body postures from
      behavioural activities. A good insight into dominance hierarchies and its
      indicators will be helpful in properly interpreting dog-dog relationships and
      diagnosing problem behaviour in dogs. 

PMID- 26309103
TI  - Clinical efficacy of hydrocodone-acetaminophen and tramadol for control of
      postoperative pain in dogs following tibial plateau leveling osteotomy.
AB  - OBJECTIVE: To evaluate clinical efficacy of hydrocodone-acetaminophen and
      tramadol for treatment of postoperative pain in dogs undergoing tibial plateau
      leveling osteotomy (TPLO). ANIMALS 50 client-owned dogs. PROCEDURES: Standardized
      anesthetic and surgical protocols were followed. Each patient was randomly
      assigned to receive either tramadol hydrochloride (5 to 7 mg/kg, PO, q 8 h;
      tramadol group) or hydrocodone bitartrate-acetaminophen (0.5 to 0.6 mg of
      hydrocodone/kg, PO, q 8 h; hydrocodone group) for analgesia after surgery. The
      modified Glasgow composite measure pain scale was used to assess signs of
      postoperative pain at predetermined intervals by an investigator who was blinded
      to treatment group. Scoring commenced with the second dose of the assigned study
      analgesic. Pain scores and rates of treatment failure (ie, dogs requiring rescue
      analgesia according to a predetermined protocol) were compared statistically
      between groups. RESULTS: 12 of 42 (29%; 5/19 in the hydrocodone-acetaminophen
      group and 7/23 in the tramadol group) dogs required rescue analgesic treatment on
      the basis of pain scores. Median pain score for the hydrocodone group was
      significantly lower than that of the tramadol group 2 hours after the second dose
      of study analgesic. The 2 groups had similar pain scores at all other time
      points. CONCLUSIONS AND CLINICAL RELEVANCE: Overall, differences in pain scores
      between dogs that received hydrocodone-acetaminophen or tramadol were minor. The
      percentage of dogs with treatment failure in both groups was considered
      unacceptable.

PMID- 26309104
TI  - Pharmacokinetics of hydrocodone and tramadol administered for control of
      postoperative pain in dogs following tibial plateau leveling osteotomy.
AB  - OBJECTIVE: To evaluate the pharmacokinetics of hydrocodone (delivered in
      combination with acetaminophen) and tramadol in dogs undergoing tibial plateau
      leveling osteotomy (TPLO). ANIMALS: 50 client-owned dogs. PROCEDURES: Dogs were
      randomly assigned to receive tramadol hydrochloride (5 to 7 mg/kg, PO, q 8 h;
      tramadol group) or hydrocodone bitartrate-acetaminophen (0.5 to 0.6 mg of
      hydrocodone/kg, PO, q 8 h; hydrocodone group) following TPLO with standard
      anesthetic and surgical protocols. Blood samples were collected for
      pharmacokinetic analysis of study drugs and their metabolites over an 8-hour
      period beginning after the second dose of the study medication. RESULTS: The
      terminal half-life, maximum serum concentration, and time to maximum serum
      concentration for tramadol following naive pooled modeling were 1.56 hours, 155.6
      ng/mL, and 3.90 hours, respectively. Serum concentrations of the tramadol
      metabolite O-desmethyltramadol (M1) were low. For hydrocodone, maximum serum
      concentration determined by naive pooled modeling was 7.90 ng/mL, and time to
      maximum serum concentration was 3.47 hours. The terminal half-life for
      hydrocodone was 15.85 hours, but was likely influenced by delayed drug absorption
      in some dogs and may not have been a robust estimate. Serum concentrations of
      hydromorphone were low. CONCLUSIONS AND CLINICAL RELEVANCE: The pharmacokinetics
      of tramadol and metabolites were similar to those in previous studies. Serum
      tramadol concentrations varied widely, and concentrations of the active M1
      metabolite were low. Metabolism of hydrocodone to hydromorphone in dogs was poor.
      Further study is warranted to assess variables that affect metabolism and
      efficacy of these drugs in dogs.

PMID- 26309105
TI  - Effects of premedication with sustained-release buprenorphine hydrochloride and
      anesthetic induction with ketamine hydrochloride or propofol in combination with
      diazepam on intraocular pressure in healthy sheep.
AB  - OBJECTIVE: To determine the effects of diazepam combined with ketamine
      hydrochloride or propofol for induction of anesthesia (IOA) following
      premedication with sustained-release buprenorphine hydrochloride (SRB) on
      intraocular pressure (IOP) in sheep. ANIMALS: 20 healthy adult sheep. PROCEDURES:
      Diazepam with ketamine or propofol was given IV to each of 10 sheep after
      premedication with SRB (0.01 mg/kg, SC); after > 4 weeks, each sheep received the
      other induction combination with no premedication. For both eyes, IOPs were
      measured before premedication (if given), 10 minutes prior to (baseline) and
      immediately following administration of ketamine or propofol (time of IOA), after
      endotracheal intubation, and 5 minutes after IOA. Peak end-tidal P(CO2), globe
      position, and pupillary diameter were also analyzed. RESULTS: Data were not
      available for all sheep for all anesthetic episodes. Propofol-diazepam
      administration alone had no significant effect on IOP, whereas there was a
      significant decrease in IOP immediately following ketamine-diazepam
      administration alone. At 5 minutes after ketamine-diazepam administration, SRB
      premedicated sheep had significantly higher IOP than unpremedicated sheep.
      Intraocular pressure was significantly higher at baseline, at intubation, and 5
      minutes after IOA in SRB-premedicated sheep receiving propofol-diazepam, compared
      with unpremedicated sheep. Peak end-tidal P(CO2) at intubation was significantly
      higher in SRB-premedicated sheep. For sheep receiving either anesthetic
      treatment, IOPs did not differ significantly with or without SRB premedication.
      Globe position or pupillary diameter and IOP were not significantly related at
      any time point. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that both
      ketamine-diazepam and propofol-diazepam combinations were suitable for IOA
      without increasing IOP in sheep. The use of SRB should be avoided in sheep when
      increases in IOP are undesirable.

PMID- 26309106
TI  - Effect of feeding a direct-fed microbial on total and antimicrobial-resistant
      fecal coliform counts in preweaned dairy calves.
AB  - OBJECTIVE: To determine whether feeding a direct-fed microbial (DFM) to dairy
      calves would reduce total and antimicrobial-resistant coliform counts in feces
      and affect average daily gain (ADG). ANIMALS: 21 preweaned Holstein heifer
      calves. PROCEDURES: The study had a randomized complete block design. Within each
      block, 3 consecutively born calves were randomly assigned to 1 of 3 treatment
      groups within 24 hours after birth (day 0). Calves were fed the DFM at 1.0 g
      (DFM1; n = 7) or 0.5 g (DFM2; 7) twice daily or no DFM (control; 7) from days 0
      through 29. A fecal sample was collected from each calf daily on days 0 through 3
      and then every other day through day 29. Fecal samples were cultured, and mean
      numbers of total coliforms and coliforms resistant to ampicillin, ceftiofur, and
      tetracycline were compared among the 3 treatment groups. Calves were weighed on
      days 0 and 29 to calculate ADG. RESULTS: Mean total fecal coliform counts did not
      differ significantly among the 3 treatment groups. Mean ceftiofur-resistant and
      tetracycline-resistant coliform counts for the control group were significantly
      lower, compared with those for the DFM1 and DFM2 groups. Mean ADG did not differ
      significantly between the DFM1 and DFM2 groups; however, the mean ADG for all
      calves fed the DFM was 0.15 kg less than that for control calves. CONCLUSION AND
      CLINICAL RELEVANCE: Results suggested that the DFM fed to the preweaned calves of
      this study did not reduce total or antimicrobial-resistant coliform counts in
      feces.

PMID- 26309107
TI  - Effect of ascorbic acid on storage of Greyhound erythrocytes.
AB  - OBJECTIVE: To assess changes in biochemical and biophysical properties of canine
      RBCs during cold (1 degrees  to 6 degrees C) storage in a licensed RBC additive
      solution (the RBC preservation solution designated AS-1) supplemented with
      ascorbic acid. SAMPLE: Blood samples from 7 neutered male Greyhounds; all dogs
      had negative results when tested for dog erythrocyte antigen 1.1. PROCEDURES:
      Blood was collected into citrate-phosphate-dextrose and stored in AS-1. Stored
      RBCs were supplemented with 7.1mM ascorbic acid or with saline (0.9% NaCl)
      solution (control samples). Several biochemical and biophysical properties of
      RBCs were measured, including percentage hemolysis, oxygen-hemoglobin
      equilibrium, and the kinetic rate constants for O2 dissociation, carbon monoxide
      association, and nitric oxide dioxygenation. RESULTS: Greyhound RBCs stored in AS
      1 supplemented with ascorbic acid did not have significantly decreased hemolysis,
      compared with results for the control samples, during the storage period.
      CONCLUSIONS AND CLINICAL RELEVANCE: In this study, ascorbic acid did not reduce
      hemolysis during storage. Several changes in stored canine RBCs were identified
      as part of the hypothermic storage lesion.

PMID- 26309108
TI  - Assessment of in vitro oxalate degradation by Lactobacillus species cultured from
      veterinary probiotics.
AB  - OBJECTIVE: To culture Lactobacillus spp from veterinary probiotics and measure
      their in vitro oxalate-degrading capacity. SAMPLE: 2 commercial veterinary
      probiotics containing Lactobacillus spp. PROCEDURES: Lactobacillus spp were
      cultured anaerobically on selective deMan, Rogosa, Sharpe agar medium and
      subcultured for speciation by 16S rDNA gene sequencing. Isolates were inoculated
      into broth containing sodium oxalate (5 mg/L) and incubated anaerobically for 72
      hours. An oxalate-degrading isolate of Lactobacillus acidophilus (American Type
      Culture Collection [ATCC] 53544) was the positive control sample; sterile broth
      containing a known quantity of sodium oxalate was the negative control sample.
      Oxalate concentrations were detected with ion chromatography. Oxalate degradation
      was assessed with Dunnett tests to detect differences in mean oxalate
      concentration for each isolate, compared with results for the negative control.
      RESULTS: Lactobacillus acidophilus, Lactobacillus plantarum, and Lactobacillus
      casei or Lactobacillus zeae (too closely related to differentiate) were isolated
      from probiotic 1, and L plantarum was isolated from probiotic 2. Sequencing of
      the 16S rDNA gene confirmed 100% homology to type species. Lactobacillus
      acidophilus (ATCC 53544) and L acidophilus from probiotic 1 significantly
      decreased oxalate concentrations by 85.3 and 161.9 mg/L, respectively.
      Lactobacillus plantarum from probiotics 1 and 2 significantly increased oxalate
      concentrations by 56.1 and 36.1 mg/L, respectively. Lactobacillus casei did not
      alter oxalate concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: Lactobacillus
      acidophilus isolates significantly reduced oxalate concentrations. In vivo
      studies are needed to determine whether probiotics containing L acidophilus
      decrease urine oxalate concentrations and reduce risk of urolith recurrence in
      dogs with a history of calcium oxalate urolithiasis.

PMID- 26309109
TI  - Attenuation of the pressor response to exogenous angiotensin by angiotensin
      receptor blockers and benazepril hydrochloride in clinically normal cats.
AB  - OBJECTIVE: To compare the attenuation of the angiotensin I-induced blood pressure
      response by once-daily oral administration of various doses of angiotensin
      receptor blockers (irbesartan, telmisartan, and losartan), benazepril
      hydrochloride, or lactose monohydrate (placebo) for 8 days in clinically normal
      cats. ANIMALS: 6 healthy cats (approx 17 months old) with surgically implanted
      arterial telemetric blood pressure-measuring catheters. PROCEDURES: Cats were
      administered orally the placebo or each of the drug treatments (benazepril [2.5
      mg/cat], irbesartan [6 and 10 mg/kg], telmisartan [0.5, 1, and 3 mg/kg], and
      losartan [2.5 mg/kg]) once daily for 8 days in a crossover study. Approximately
      90 minutes after capsule administration on day 8, each cat was anesthetized and
      arterial blood pressure measurements were recorded before and after IV
      administration of each of 4 boluses of angiotensin I (20, 100, 500, and 1,000
      ng/kg). This protocol was repeated 24 hours after benazepril treatment and
      telmisartan (3 mg/kg) treatment. Differences in the angiotensin I-induced change
      in systolic arterial blood pressure (DeltaSBP) among treatments were determined.
      RESULTS: At 90 minutes after capsule administration, only losartan did not
      significantly reduce DeltaSBP in response to the 3 higher angiotensin doses,
      compared with placebo. Among drug treatments, telmisartan (3 mg/kg dosage)
      attenuated DeltaSBP to a significantly greater degree than benazepril and all
      other treatments. At 24 hours, telmisartan was more effective than benazepril
      (mean +/- SEM DeltaSBP, 15.7 +/- 1.9 mm Hg vs 55.9 +/- 12.42 mm Hg,
      respectively). CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that
      telmisartan administration may have advantages over benazepril administration for
      cats with renal or cardiovascular disease.

PMID- 26309110
TI  - Comparison of the characteristics and multipotential and in vivo cartilage
      formation capabilities between porcine adipose-derived stem cells and porcine
      skin-derived stem cell-like cells.
AB  - OBJECTIVE: To compare the characteristics and multipotential and in vivo
      cartilage formation capabilities of porcine adipose-derived stem cells (pASCs)
      with those of porcine skin-derived stem cell-like cells (pSSCs). ANIMALS: Three 6
      month-old female pigs and four 6-week-old female athymic mice. PROCEDURES:
      Adipose and skin tissue specimens were obtained from each pig following slaughter
      and digested to obtain pASCs and pSSCs. For each cell type, flow cytometry and
      reverse transcription PCR assays were performed to characterize the expression of
      cell surface and mesenchymal stem cell markers, and in vitro cell cultures were
      performed to determine the adipogenic, osteogenic, and chondrogenic capabilities.
      Each cell type was then implanted into athymic mice to determine the extent of in
      vivo cartilage formation after 6 weeks. RESULTS: The cell surface and mesenchymal
      stem cell marker expression patterns, multipotential capability, and extent of in
      vivo cartilage formation did not differ significantly between pASCs and pSSCs.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that pSSCs may be a viable
      alternative to pASCs as a source of progenitor cells for tissue engineering in
      regenerative medicine.

PMID- 26309111
TI  - Characteristics of canine platelet-rich plasma prepared with five commercially
      available systems.
AB  - OBJECTIVE: To characterize platelet-rich plasma (PRP) products obtained from
      canine blood by use of a variety of commercially available devices. SAMPLE: Blood
      samples from 15 dogs between 18 months and 9 years of age with no concurrent
      disease, except for osteoarthritis in some dogs. PROCEDURES: PRP products were
      produced from blood obtained from each of the 15 dogs by use of each of 5
      commercially available PRP-concentrating systems. Complete blood counts were
      performed on each whole blood sample and PRP product. The degree of platelet,
      leukocyte, and erythrocyte concentration or reduction for PRP, compared with
      results for the whole blood sample, was quantified for each dog and summarized
      for each concentrating system. RESULTS: The various PRP-concentrating systems
      differed substantially in the amount of blood processed, method of PRP
      preparation, amount of PRP produced, and platelet, leukocyte, and erythrocyte
      concentrations or reductions for PRP relative to results for whole blood.
      CONCLUSIONS AND CLINICAL RELEVANCE: The characteristics of PRP products differed
      considerably. Investigators evaluating the efficacy of PRPs need to specify the
      characteristics of the product they are assessing. Clinicians should be aware of
      the data (or lack of data) supporting use of a particular PRP for a specific
      medical condition.

PMID- 26309112
TI  - Estimation of glomerular filtration rate in dogs by a single-blood sample method
      involving iodixanol.
AB  - OBJECTIVE: To establish a simplified single-blood-sample method (SBSM) involving
      iodixanol to estimate glomerular filtration rate (GFR) in dogs and compare data
      provided by that procedure with data provided by a conventional multiple-blood
      sample method (MBSM) involving inulin. ANIMALS: 26 healthy dogs and 36 dogs with
      naturally occurring renal disease. PROCEDURES: Dogs were used in various
      preliminary experiments to establish protocols for the SBSM and the MBSM of GFR
      estimation. To evaluate the relationship between GFRs obtained by the SBSM and
      the MBSM each involving iodixanol, iodixanol (40 mg of I/kg) was administered IV
      to 26 healthy dogs and 36 dogs with renal disease; blood sample collection was
      performed before and at 60, 90, and 120 minutes after the injection. To evaluate
      the relationship between GFRs obtained by the SBSM involving iodixanol and the
      MBSM involving inulin, iodixanol (40 mg of I/kg) and inulin (50 mg/kg) were
      coadministered IV to 22 healthy dogs and 3 dogs with renal disease, followed by
      blood sample collection 30, 60, 90, and 120 minutes later. Serum iodixanol and
      inulin concentrations were separately determined by reverse-phase high
      performance liquid chromatography. RESULTS: Findings revealed a correlation (r =
      0.99) between GFR estimated by the SBSM and MBSM each involving iodixanol.
      Likewise, GFR estimated by the SBSM involving iodixanol was correlated (r = 0.89)
      with that estimated by the MBSM involving inulin. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results indicated that the SBSM involving iodixanol can be applied to
      estimate GFR in dogs, instead of use of an MBSM.

PMID- 26309113
TI  - A New Dimension in Documenting New Species: High-Detail Imaging for Myriapod
      Taxonomy and First 3D Cybertype of a New Millipede Species (Diplopoda, Julida,
      Julidae).
AB  - We review the state-of-the-art approaches currently applied in myriapod taxonomy,
      and we describe, for the first time, a new species of millipede (Ommatoiulus
      avatar n. sp., family Julidae) using high-resolution X-ray microtomography
      (microCT) as a substantive adjunct to traditional morphological examination. We
      present 3D models of the holotype and paratype specimens and discuss the
      potential of this non-destructive technique in documenting new species of
      millipedes and other organisms. The microCT data have been uploaded to an open
      repository (Dryad) to serve as the first actual millipede cybertypes to be
      published. 

PMID- 26309114
TI  - New algorithm of mortality risk prediction for cardiovascular patients admitted
      in intensive care unit.
AB  - OBJECTIVE: Recognizing and managing of admitted patients in intensive care unit
      (ICU) with high risk of mortality is important for maximizing the patient's
      outcomes and minimizing the costs. This study is based on linear and nonlinear
      analysis of heart rate variability (HRV) to design a classifier for mortality
      prediction of cardio vascular patients admitted to ICU. METHODS: In this study we
      evaluated 90 cardiovascular ICU patients (45 males and 45 females). Linear and
      nonlinear features of HRV include SDNN, NN50, low frequency (LF), high frequency
      (HF), correlation dimension, approximate entropy; detrended fluctuation analysis
      (DFA) and Poincare plot were analyzed. Paired sample t-test was used for
      statistical comparison. Finally, we fed these features to the Multi-Layer
      Perceptron (MLP) and Support Vector Machines (SVMs) to find a robust
      classification method to classify the patients with low risk and high risk of
      death. RESULTS: Almost all HRV features measuring heart rate complexity were
      significantly decreased in the episode of half-hour before death. The results
      generated based on SVM and MLP classifiers show that SVM classifier is enable to
      distinguish high and low risk episodes with the total classification sensitivity,
      specificity, positive productivity and accuracy rate of 97.3%, 98.1%, 92.5% and
      99.3%, respectively. CONCLUSIONS: The results of the current study suggest that
      nonlinear features of the HRV signals could be show nonlinear dynamics.

PMID- 26309115
TI  - The Evolution of Epigean and Stygobitic Species of Koonunga Sayce, 1907
      (Syncarida: Anaspidacea) in Southern Australia, with the Description of Three New
      Species.
AB  - Three new species of Koonunga were discovered in surface and subterranean waters
      in southern Australia, and were defined using mtDNA analyses and morphology. The
      new species are: Koonunga hornei Leijs & King; K. tatiaraensis Leijs & King and
      K. allambiensis Leijs & King. Molecular clock analyses indicate that the
      divergence times of the species are older than the landscape that they currently
      inhabit. Different scenarios explaining this apparent discrepancy are discussed
      in the context of the palaeography of the area. A freshwater epigean origin for
      Koonunga is considered the most likely hypothesis, whereby some lineages made the
      transition to the subterranean environment within the last few million years
      influenced by significant climatic cooling/drying. We discuss the possibility
      that one stygobitic lineage secondarily regained some of its body pigmentation as
      adaptation to increased photic conditions after cave collapse and forming of
      cenotes during the last glacial maximum. 

PMID- 26309116
TI  - Facile kinetic induction of a dihydropyridide to pyrrolide ring contraction.
AB  - Reactions between magnesium 1,4-dihydropyridide or 1,2-dihydro-iso-quinolide
      derivatives and carbodiimides, RN[double bond, length as m-dash]C[double bond,
      length as m-dash]NR, generally result in Mg-N insertion and formation of
      guanidinate complexes. More sterically perturbed systems with N-aryl carbodiimide
      substitution, however, follow a divergent course of reaction initiating
      heterocyclic ring contraction and pyrrolide formation under unprecedentedly mild
      conditions. 

PMID- 26309117
TI  - Liver Transplantation for Pediatric Hepatoblastoma and Hepatocellular Carcinoma:
      Out of the Unknown.

PMID- 26309118
TI  - A Quality of Working Life Survey Instrument for Hospital Nurses.
AB  - BACKGROUND: The high turnover rate for hospital nurses worldwide means that some
      nursing staff remain at their posts for only a few months. To fully understand
      the problem, it is necessary to evaluate the concepts, constructs, and units of
      the working life of professional nurses. Previous qualitative work has identified
      and defined an initial set of items relevant to the working life of nurses.
      Therefore, the aim of this research is to develop a valid questionnaire for use
      in further examining the working life quality of nurses. PURPOSE: This article
      reports on the development of a questionnaire that is valid and reliable for
      examining the quality of working life of nurses. METHODS: Qualitative and
      quantitative data collection methods were employed within two medical centers and
      six regional hospitals in Taiwan. Seven hundred registered nurses in medical or
      surgical wards with at least 2 years of nursing experience and a position below
      assistant manager in a medical or surgical ward were included as participants.
      RESULTS: Previous qualitative research findings generated items for the
      questionnaire with content and construct. Six scales with 33 factors were
      identified. The scales addressed the aspects of organization, work, self
      actualization, interrelationships, self-efficacy, and vocational concepts. These
      factors explained 63% of the total variance. The Cronbach's alphas ranged from
      .80 to .89, indicating acceptable internal consistency. CONCLUSIONS/IMPLICATIONS
      FOR PRACTICE: The information obtained using the questionnaire may improve
      workplace audit outcomes, promote occupational health, and improve service
      quality.

PMID- 26309119
TI  - Investigation on graphene and Pt co-modified CdS nanowires with enhanced
      photocatalytic hydrogen evolution activity under visible light irradiation.
AB  - Hydrogen evolution by photocatalytic water splitting has attracted extensive
      attention in recent years. Here we report a composite photocatalyst, in which
      graphene and Pt particles act as cocatalysts to modify CdS nanowires. This
      composite photocatalyst was prepared by a solvothermal method followed by a
      photoreduction process. The obtained samples were characterized by X-ray powder
      diffraction, UV-vis diffuse reflectance spectroscopy, scanning and transmission
      electron microscopy, X-ray photoelectron spectroscopy, photoluminescence and
      Brunauer-Emmett-Teller specific surface area analysis. The graphene and Pt
      comodified CdS nanowires gain a high hydrogen evolution rate of 3984 MUmol h(-1)
      g(-1), which is almost 4 times higher than that of bare CdS nanowires and also
      higher than the sum of graphene-CdS and Pt-CdS nanowires. The obtained sample
      also exhibits a good stability. The encouraging results presented here can be
      attributed to the incorporation of graphene and Pt which show a synergetic effect
      for hydrogen evolution. This work paves a way to the potential application of CdS
      nanowires in energy conversion. 

PMID- 26309120
TI  - Statins, HMG-CoA Reductase Inhibitors, Improve Neovascularization by Increasing
      the Expression Density of CXCR4 in Endothelial Progenitor Cells.
AB  - Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase,
      are used to reduce cholesterol biosynthesis in the liver. Accordingly, statins
      regulate nitric oxide (NO) and glutamate metabolism, inflammation, angiogenesis,
      immunity and endothelial progenitor cells (EPCs) functions. The function of EPCs
      are regulated by stromal cell-derived factor 1 (SDF-1), vascular endothelial
      growth factor (VEGF), and transforming growth factor beta (TGF-beta), etc. Even
      though the pharmacologic mechanisms by which statins affect the neovasculogenesis
      of circulating EPCs, it is still unknown whether statins affect the EPCs function
      through the regulation of CXCR4, a SDF-1 receptor expression. Therefore, we
      desired to explore the effects of statins on CXCR4 expression in EPC-mediated
      neovascularization by in vitro and in vivo analyses. In animal studies, we
      analyzed the effects of atorvastatin or rosuvastatin treatments in recovery of
      capillary density and blood flow, the expression of vWF and CXCR4 at ischemia
      sites in hindlimb ischemia ICR mice. Additionally, we analyzed whether the
      atorvastatin or rosuvastatin treatments increased the mobilization, homing, and
      CXCR4 expression of EPCs in hindlimb ischemia ICR mice that underwent bone marrow
      transplantation. The results indicated that statins treatment led to
      significantly more CXCR4-positive endothelial progenitor cells incorporated into
      ischemic sites and in the blood compared with control mice. In vivo, we isolated
      human EPCs and analyzed the effect of statins treatment on the vasculogenic
      ability of EPCs and the expression of CXCR4. Compared with the control groups,
      the neovascularization ability of EPCs was significantly improved in the
      atorvastatin or rosuvastatin group; this improvement was dependent on CXCR4 up
      regulation. The efficacy of statins on improving EPC neovascularization was
      related to the SDF-1alpha/CXCR4 axis and might be regulated by the NO. In
      conclusion, atorvastatin and rosuvastatin improved neovascularization in hindlimb
      ischemia mice; this effect may have been mediated by increased CXCR4 expression
      in EPCs. 

PMID- 26309121
TI  - Aortic Stiffness and Cardiovascular Risk in Women with Previous Gestational
      Diabetes Mellitus.
AB  - Gestational diabetes mellitus (GDM) is a significant risk factor for
      cardiovascular disease (CVD) in later life, but the mechanism remains unclear.
      The aim of the study was to investigate indices of glucose metabolism,
      dyslipidemia, and arterial stiffness (as measured by pulse wave velocity (PWV)),
      in women with and without a history of GDM, using both the old WHO and new IADPSG
      diagnostic criteria, at 5 years after the index pregnancy. Dyslipidemia and PWV
      were used as surrogate markers for CVD risk. The population-based prospective
      cohort included 300 women from the original STORK study. All participants had an
      oral glucose tolerance test (OGTT) during pregnancy. Five years later, the OGTT
      was repeated along with dual-energy x-ray absorptiometry, lipid analysis, and PWV
      analysis. Measurements were compared between those women who did and did not have
      GDM based on both the WHO and IADPSG criteria. We found that women with GDM based
      on the old WHO criteria had higher CVD risk at 5 years than those without GDM,
      with markedly elevated PWV and more severe dyslipidemia (higher triglycerides
      (TG)/HDL cholesterol ratio). After adjusting for known risk factors, the most
      important predictors for elevated PWV and TG/HDL-C ratio at 5-year follow-up were
      maternal age, BMI, GDM, systolic blood pressure, and indices of glucose
      metabolism in the index pregnancy. In conclusion, we found a higher risk for CVD,
      based on the surrogate markers PWV and TG/HDL-C ratio, at 5-year follow-up in
      women diagnosed with GDM in the index pregnancy when using the old WHO diagnostic
      criteria. 

PMID- 26309122
TI  - Pyrimidinedione-mediated selective histone deacetylase 6 inhibitors with
      antitumor activity in colorectal cancer HCT116 cells.
AB  - We synthesized a series of pyrimidinedione derivatives and evaluated their
      activities. The results indicate that compound 6, 4-[5-fluoro-2,6-dioxo-3
      (tetrahydro-furan-2-yl)-3,6-dihydro-2H-pyrimidin-1-ylmethyl]-N-hydroxy-benzamide,
      exhibits potent antiproliferative activity, apoptosis induction with cleavage of
      caspase and PARP, and enhanced tendency to inhibit HDAC6 (IC50 = 12.4 nM)
      activity over HDAC1 (IC50 = 1710 nM) and HDAC2 (IC50 = 5500 nM). Compound 6 also
      inhibits tumor growth and is less toxic than parent 4 in vivo. These data provide
      compelling evidence that compound 6 is a potential antitumor compound with HDAC6
      targeted inhibitory activity and may be tested for preclinical investigation for
      cancer treatment.

PMID- 26309123
TI  - Phase-modulated electronic wave packet interferometry reveals high resolution
      spectra of free Rb atoms and Rb*He molecules.
AB  - Phase-modulated wave packet interferometry is combined with mass-resolved
      photoion detection to investigate rubidium atoms attached to helium nanodroplets
      in a molecular beam experiment. The spectra of atomic Rb electronic states show a
      vastly enhanced sensitivity and spectral resolution when compared to conventional
      pump-probe wave packet interferometry. Furthermore, the formation of Rb*He
      exciplex molecules is probed and for the first time a fully resolved vibrational
      spectrum for transitions between the lowest excited 5Pi3/2 and the high-lying
      electronic states 2(2)Pi, 4(2)Delta, 6(2)Sigma is obtained and compared to
      theory. The feasibility of applying coherent multidimensional spectroscopy to
      dilute cold gas phase samples is demonstrated in these experiments. 

PMID- 26309125
TI  - Microwave spectroscopic and theoretical investigations of the strongly hydrogen
      bonded hexafluoroisopropanol...water complex.
AB  - This paper reports microwave spectroscopic and theoretical investigations on the
      interaction of water with hexafluoroisopropanol (HFIP). The HFIP monomer can
      exist in two conformations, antiperiplanar (AP) and synclinical (SC). The former
      is about 5 kJ mol(-1) more stable than the latter. Theoretical calculations
      predicted three potential minima for the complex, two having AP and one having SC
      conformations. Though, the binding energy for the HFIP(SC)...H2O turned out to be
      larger than that for the other two conformers having HFIP in the AP form, the
      global minimum for the complex in the potential energy hypersurface had HFIP in
      the AP form. Experimental rotational constants for four isotopologues measured
      using a pulsed nozzle Fourier transform microwave spectrometer, correspond to the
      global minimum in the potential energy hypersurface. The structural parameters
      and the internal dynamics of the complex could be determined from the rotational
      spectra of the four isotopologues. The global minimum has the HFIP(AP) as a
      hydrogen bond donor forming a strong hydrogen bond with H2O. To characterize the
      strength of the bonding and to probe the other interactions within the complex,
      atoms in molecules, non-covalent interaction index and natural bond orbital
      theoretical analyses have been performed.

PMID- 26309124
TI  - Seizure Outcomes and Predictors of Recurrent Post-Stroke Seizure: A Retrospective
      Observational Cohort Study.
AB  - BACKGROUND: Seizure is a common complication after stroke (termed "post-stroke
      seizure," PSS). Although many studies have assessed outcomes and risk factors of
      PSS, no reliable predictors are currently available to determine PSS recurrence.
      We compared baseline clinical characteristics and post-stroke treatment regimens
      between recurrent and non-recurrent PSS patients to identify factors predictive
      of recurrence. METHODS: Consecutive PSS patients admitted to our stroke center
      between January 2011 and July 2013 were monitored until February 2014 (median 357
      days; IQR, 160-552) and retrospectively evaluated for baseline clinical
      characteristics and PSS recurrence. Cumulative recurrence rates at 90, 180, and
      360 days post-stroke were estimated by Kaplan-Meier analysis. Independent
      predictors of recurrent PSS were identified by Cox proportional-hazards analysis.
      RESULTS: A total of 104 patients (71 men; mean age, 72.1 +/- 11.2 years) were
      analyzed. PSS recurred in 31 patients (30%) during the follow-up. Factors
      significantly associated with PSS recurrence by log-rank analysis included
      previous PSS, valproic acid (VPA) monotherapy, polytherapy with antiepileptic
      drugs (AEDs), frontal cortical lesion, and higher modified Rankin Scale score at
      discharge (all p < 0.05). Independent predictors of recurrent PSS were age <74
      years (HR 2.38, 95% CI 1.02-5.90), VPA monotherapy (HR 3.86, 95% CI 1.30-12.62),
      and convulsions on admission (HR 3.87, 95% CI 1.35-12.76). CONCLUSIONS:
      Approximately one-third of PSS patients experienced seizure recurrence within one
      year. The predictors of recurrent PSS were younger age, presence of convulsions
      and VPA monotherapy. Our findings should be interpreted cautiously in countries
      where monotherapy with second-generation AEDs has been approved because this
      study was conducted while second-generation AEDs had not been officially approved
      for monotherapy in Japan.

PMID- 26309126
TI  - Understanding Barriers for Communicating Injury Prevention Messages and
      Strategies Moving Forward: Perspectives from Community Stakeholders.
AB  - OBJECTIVES: The primary objective of this study was to elicit the perspectives of
      direct care providers on barriers and facilitators to communicating injury
      prevention messages to parents/caregivers of children under 4 years of age. The
      secondary objective was to examine characteristics of an injury prevention
      messaging strategy preferred by direct care providers. DESIGN AND SAMPLE: This
      qualitative study was conducted across four regions in Ontario Canada. Fifty-nine
      direct care providers were purposefully sampled and data interpreted using focus
      group analysis. MEASURES: Transcripts were analyzed verbatim using content and
      discourse analysis. RESULTS: Several barriers to communicating injury prevention
      messages were identified encompassing (a) role, (b) parental, (c) social
      determinants, and (d) evidence impediments. In an effort to offset some of these
      barriers, participants endorsed the development of a tailored multicomponent
      injury prevention strategy adopting action-based messages. CONCLUSION: The
      results of this study provide an in-depth exploration of direct care providers
      perceptions that can inform the design of materials and dissemination strategies
      to help increase and optimize access to injury prevention information. Injury
      prevention messages should be action-oriented, specifically tailored to the stage
      of child development, and disseminated through both face-to-face interactions and
      mobile technology.

PMID- 26309127
TI  - Generation of Monoclonal Antibodies against Dengue Virus Type 4 and
      Identification of Enhancing Epitopes on Envelope Protein.
AB  - The four serotypes of dengue virus (DENV1-4) pose a serious threat to global
      health. Cross-reactive and non-neutralizing antibodies enhance viral infection,
      thereby exacerbating the disease via antibody-dependent enhancement (ADE).
      Studying the epitopes targeted by these enhancing antibodies would improve the
      immune responses against DENV infection. In order to investigate the roles of
      antibodies in the pathogenesis of dengue, we generated a panel of 16 new
      monoclonal antibodies (mAbs) against DENV4. Using plaque reduction neutralization
      test (PRNT), we examined the neutralizing activity of these mAbs. Furthermore, we
      used the in vitro and in vivo ADE assay to evaluate the enhancement of DENV
      infection by mAbs. The results indicate that the cross-reactive and poorly
      neutralizing mAbs, DD11-4 and DD18-5, strongly enhance DENV1-4 infection of K562
      cells and increase mortality in AG129 mice. The epitope residues of these
      enhancing mAbs were identified using virus-like particle (VLP) mutants. W212 and
      E26 are the epitope residues of DD11-4 and DD18-5, respectively. In conclusion,
      we generated and characterized 16 new mAbs against DENV4. DD11-4 and D18-5
      possessed non-neutralizing activities and enhanced viral infection. Moreover, we
      identified the epitope residues of enhancing mAbs on envelope protein. These
      results may provide useful information for development of safe dengue vaccine. 

PMID- 26309128
TI  - Continuation versus discontinuation of oxytocin infusion during the active phase
      of labour: a randomised controlled trial.
AB  - OBJECTIVE: To investigate whether discontinuation of oxytocin infusion increases
      the duration of the active phase of labour and reduces maternal and neonatal
      complications. DESIGN: Randomised controlled trial. SETTING: Department of
      Obstetrics and Gynaecology, Regional Hospital of Randers, Denmark. POPULATION:
      Women with singleton pregnancy in the vertex position undergoing labour induction
      or augmentation. METHODS: Two hundred women were randomised when cervical
      dilation was <=4 cm to either continue or discontinue oxytocin infusion when
      cervical dilation reached 5 cm. MAIN OUTCOME MEASURES: The primary outcome was
      duration of the active phase of labour, defined as the time period from 5 cm of
      cervical dilation until delivery. Secondary outcomes were mode of delivery,
      uterine tachysystole, hyperstimulation, abnormalities in fetal heart rate,
      postpartum haemorrhage rate, perineal tears, and neonatal outcomes. RESULTS: The
      active phase of labour was longer by 41 minutes (95% confidence interval 11-75
      minutes) in the discontinued group (median 125 minutes in 85 women who had
      reached the active phase and delivered vaginally) versus the continued group
      (median 88 minutes in 78 women). The incidence of fetal heart rate abnormalities
      (51 versus 20%) and uterine hyperstimulation (12 versus 2%) was significantly
      greater in the continued than the discontinued oxytocin group. The incidence of
      tachysystole, caesarean deliveries, postpartum haemorrhage, third degree perineal
      tears and adverse neonatal outcomes was higher in the continued group, but did
      not reach significance. CONCLUSIONS: Discontinuation of oxytocin infusion in the
      active phase of labour may improve some labour outcomes but has the disadvantage
      of increasing the duration of the active phase of labour. TWEETABLE ABSTRACT:
      Stopping oxytocin in the active phase seems to make labour less complicated but
      lengthens duration.

PMID- 26309129
TI  - Protein-Containing Multilayer Capsules by Templating on Mesoporous CaCO3
      Particles: POST- and PRE-Loading Approaches.
AB  - Encapsulation of model proteins (catalase, insulin, aprotinin) into multilayer
      dextran sulphate/protamin capsules by templating on CaCO3 microparticles is
      investigated employing: (i) PRE-loading into CaCO3 particles by adsorption or co
      synthesis and (ii) POST-loading into performed capsules. Protein encapsulation is
      governed by both its size and electrostatic interactions with the carbonate
      microparticles and multilayer shell. PRE-loading enables improved encapsulation
      compared to POST-loading (catalase content in capsules 630 and 70 mg . g(-1)).
      Bioactivity of encapsulated protein is not affected by interaction with
      multilayers but may be reduced at slightly alkaline pH due to CaCO3 hydrolysis.
      This study might help to successfully encapsulate fragile bio-macromolecules into
      multilayer capsules.

PMID- 26309130
TI  - Phylogenetic Co-Occurrence of ExoR, ExoS, and ChvI, Components of the RSI
      Bacterial Invasion Switch, Suggests a Key Adaptive Mechanism Regulating the
      Transition between Free-Living and Host-Invading Phases in Rhizobiales.
AB  - Both bacterial symbionts and pathogens rely on their host-sensing mechanisms to
      activate the biosynthetic pathways necessary for their invasion into host cells.
      The Gram-negative bacterium Sinorhizobium meliloti relies on its RSI (ExoR-ExoS
      ChvI) Invasion Switch to turn on the production of succinoglycan, an
      exopolysaccharide required for its host invasion. Recent whole-genome sequencing
      efforts have uncovered putative components of RSI-like invasion switches in many
      other symbiotic and pathogenic bacteria. To explore the possibility of the
      existence of a common invasion switch, we have conducted a phylogenomic survey of
      orthologous ExoR, ExoS, and ChvI tripartite sets in more than ninety
      proteobacterial genomes. Our analyses suggest that functional orthologs of the
      RSI invasion switch co-exist in Rhizobiales, an order characterized by numerous
      invasive species, but not in the order's close relatives. Phylogenomic analyses
      and reconstruction of orthologous sets of the three proteins in
      Alphaproteobacteria confirm Rhizobiales-specific gene synteny and congruent RSI
      evolutionary histories. Evolutionary analyses further revealed site-specific
      substitutions correlated specifically to either animal-bacteria or plant-bacteria
      associations. Lineage restricted conservation of any one specialized gene is in
      itself an indication of species adaptation. However, the orthologous phylogenetic
      co-occurrence of all interacting partners within this single signaling pathway
      strongly suggests that the development of the RSI switch was a key adaptive
      mechanism. The RSI invasion switch, originally found in S. meliloti, is a
      characteristic of the Rhizobiales, and potentially a conserved crucial activation
      step that may be targeted to control host invasion by pathogenic bacterial
      species. 

PMID- 26309131
TI  - Prognostic Value of CD11b Expression Level for Acute Myeloid Leukemia Patients: A
      Meta-Analysis.
AB  - BACKGROUND: Study results on the prognostic value of CD11b for acute myeloid
      leukemia (AML) patients are inconsistent. An up-to-date meta-analysis was
      conducted to assess the prognostic value of CD11b expression level for AML
      patients. METHODS: Electronic databases including PubMed, Embase, Cochrane
      Library, Web of Science and Chinese BioMedical Literature Database (CBM) were
      searched to identify studies that investigated the association between CD11b
      expression level and prognosis of AML patients. Pooled hazard ratios (HRs) with
      95% confidence intervals (CIs) for overall survival (OS) and disease-free
      survival (DFS) and pooled odds ratio (OR) with 95% CI for complete remission rate
      (CRR) were calculated using Revman 5.3 and Stata 11.0. RESULTS: 13 total studies
      with 2619 patients were included in this meta-analysis. Results of the meta
      analysis showed that CD11b positivity was associated with lower CRR (OR = 0.44;
      95% CI, 0.25-0.79; p = 0.006) and shorter OS (HR = 0.66; 95% CI, 0.55-0.80; p <
      0.0001), but did not affect DFS (HR = 0.67; 95% CI, 0.31-1.48; p = 0.32).
      Subgroup analysis by ethnicity, cut-off value for CD11b positivity, treatment,
      subtype and sample preparation method showed no significant interaction between
      these factors with the prognostic value of CD11b expression level for AML
      patients. Sensitivity analysis yielded consistent results with the main meta
      analysis. CONCLUSION: CD11b positivity could predict a poor prognosis for AML
      patients. Thus, CD11b expression level might be considered a prognostic biomarker
      for AML patients.

PMID- 26309133
TI  - Acute-phase response following full-mouth versus quadrant non-surgical
      periodontal treatment: A randomized clinical trial.
AB  - AIM: A moderate acute-phase response occurs 24-h following full-mouth non
      surgical treatment (FM-SRP). The aim of this study was to compare acute-phase (24
      h) and medium-term (3 months) inflammation after quadrant scaling (Q-SRP) versus
      FM-SRP. MATERIAL & METHODS: Thirty-eight periodontitis-affected subjects were
      randomly allocated to FM-SRP or Q-SRP after a baseline visit. Periodontal and
      anthropometric parameters were collected at baseline and 3 months. Serum samples
      were drawn at baseline, 1, 7, and 90 days after treatment. High-sensitivity
      assays of inflammation and endothelial assays were performed. RESULTS: FM-SRP
      produced a greater acute-phase response after 24 h [threefold increase in C
      reactive protein (CRP), twofold increase in interleukin (IL-6), and a slight
      increase in tumour necrosis factor]. No differences in systemic biomarkers were
      noted between groups at any later follow-ups. Both periodontal treatments
      produced a comparable improvement in clinical periodontal parameters with no
      between-group differences. Treatment time was positively associated with the
      relative 24-h increase in CRP (R = 0.5, p < 0.001) and IL-6 (R = 0.5, p = 0.002),
      while the number of deeper (>6 mm) pockets predicted only the relative increase
      in IL-6 (R = 0.4, p < 0.05). CONCLUSIONS: FM-SRP triggers a moderate acute-phase
      response of 24 h duration compared to Q-SRP. Further research is needed to assess
      the eventual impact of such findings on the risk of vascular events is advocated.
      (ClinicalTrials.gov NCT01857804).

PMID- 26309132
TI  - Phytometabolite Dehydroleucodine Induces Cell Cycle Arrest, Apoptosis, and DNA
      Damage in Human Astrocytoma Cells through p73/p53 Regulation.
AB  - Accumulating evidence supports the idea that secondary metabolites obtained from
      medicinal plants (phytometabolites) may be important contributors in the
      development of new chemotherapeutic agents to reduce the occurrence or recurrence
      of cancer. Our study focused on Dehydroleucodine (DhL), a sesquiterpene found in
      the provinces of Loja and Zamora-Chinchipe. In this study, we showed that DhL
      displayed cytostatic and cytotoxic activities on the human cerebral astrocytoma
      D384 cell line. With lactone isolated from Gynoxys verrucosa Wedd, a medicinal
      plant from Ecuador, we found that DhL induced cell death in D384 cells by
      triggering cell cycle arrest and inducing apoptosis and DNA damage. We further
      found that the cell death resulted in the increased expression of CDKN1A and BAX
      proteins. A marked induction of the levels of total TP73 and phosphorylated TP53,
      TP73, and gamma-H2AX proteins was observed in D384 cells exposed to DhL, but no
      increase in total TP53 levels was detected. Overall these studies demonstrated
      the marked effect of DhL on the diminished survival of human astrocytoma cells
      through the induced expression of TP73 and phosphorylation of TP73 and TP53,
      suggesting their key roles in the tumor cell response to DhL treatment. 

PMID- 26309134
TI  - Pretreatment anxiety and pain acceptance are associated with response to trigger
      point injection therapy for chronic myofascial pain.
AB  - BACKGROUND AND AIM: This study examined the psychosocial profile of patients who
      responded or did not respond to trigger point injection therapy for chronic
      myofascial pain. METHODS: Seventy one patients with a diagnosis of chronic
      myofascial pain of the paraspinous muscles completed a pretreatment questionnaire
      measuring demographic and social factors, and validated scales to assess pain
      intensity, pain interference (physical and emotional), and defined psychological
      characteristics (pain catastrophizing, pain acceptance, pain self-efficacy, mood
      and anxiety). Trigger point injection therapy of the affected areas of myofascial
      pain was performed and follow-up was conducted by telephone at one week (n = 65)
      and one month (n = 63) post intervention to assess treatment outcome (pain
      intensity and pain-related physical interference). RESULTS: At one week follow-up
      and one-month follow-up, using pain-related physical interference as the outcome
      measure, we found that those who responded well to treatment were characterized
      by a lower level of pretreatment anxiety and a higher level of pain acceptance,
      with anxiety being the strongest predictor. CONCLUSION: These results suggest
      that responses to interventional pain management in chronic myofascial
      paraspinous pain may be influenced by psychological characteristics, especially
      pretreatment anxiety.

PMID- 26309135
TI  - (Z)-Stereoselective Synthesis of Mono- and Bis-heterocyclic Benzimidazol-2-ones
      via Cascade Processes Coupled with the Ugi Multicomponent Reaction.
AB  - Several novel cascade reactions are herein reported that enable access to a
      variety of unique mono- and bis-heterocyclic scaffolds. The sequence of cascade
      events are mediated through acid treatment of an Ugi adduct that affords 1,5
      benzodiazepines which subsequently undergo an elegant rearrangement to deliver
      (E)-benzimidazolones, which through acid-promoted tautomerization convert to
      their corresponding (Z)-isomers. Moreover, a variety of heterocycles tethered to
      (Z)-benzimidazole-2-ones are also accessible through similar domino-like
      processes, demonstrating a general strategy to access significantly new scaffold
      diversity, each containing four points of potential diversification. Final
      structures of five scaffolds have been definitively proven by X-ray
      crystallography. 

PMID- 26309136
TI  - Human Schwann-like cells derived from adipose-derived mesenchymal stem cells
      rapidly de-differentiate in the absence of stimulating medium.
AB  - Finding a viable cell-based therapy to address peripheral nerve injury holds
      promise for enhancing the currently suboptimal microsurgical approaches to
      peripheral nerve repair. Autologous nerve grafting is the current gold standard
      for surgical repair of nerve gaps; however, this causes donor nerve morbidity in
      the patient, and the results remain unsatisfactory. Transplanting autologous
      Schwann cells (SCs) results in similar morbidity, as well as limited cell numbers
      and restricted potential for expansion in vitro. Adipose-derived stem cells
      (ASCs), 'differentiated' towards an SC-like phenotype in vitro (dASCs), have been
      presented as an alternative to SC therapies. The differentiation protocol
      stimulates ASCs to mimic the SC phenotype; however, the efficacy of dASCs in
      nerve repair is not yet convincing, and the practicality of the SC-like phenotype
      is unproven. Here, we examined the stability of dASCs by withdrawing
      differentiation medium for 72 h after the full 18-day differentiation protocol,
      and measuring changes in morphology, gene expression, and protein levels.
      Withdrawal of differentiation medium from dASCs resulted in a rapid reversion to
      stem cell-like characteristics. Quantitative real-time polymerase chain reaction
      and enzyme-linked immunosorbent assay analyses demonstrated a significant
      reduction in gene and protein expression of growth factors that were expressed at
      high levels following 'differentiation'. Therefore, we question the relevance of
      differentiation to an SC-like phenotype, as withdrawal of differentiation medium,
      a model of transplantation into an injured nerve, results in rapid reversion of
      the dASC phenotype to stem cell-like characteristics. Further investigation into
      the differentiation process and the response of dASCs to an injured environment
      must be undertaken prior to the use of dASCs in peripheral nerve repair
      therapies.

PMID- 26309137
TI  - Effects of Long Term Antibiotic Therapy on Human Oral and Fecal Viromes.
AB  - Viruses are integral members of the human microbiome. Many of the viruses
      comprising the human virome have been identified as bacteriophage, and little is
      known about how they respond to perturbations within the human ecosystem. The
      intimate association of phage with their cellular hosts suggests their
      communities may change in response to shifts in bacterial community membership.
      Alterations to human bacterial biota can result in human disease including a
      reduction in the host's resilience to pathogens. Here we report the ecology of
      oral and fecal viral communities and their responses to long-term antibiotic
      therapy in a cohort of human subjects. We found significant differences between
      the viral communities of each body site with a more heterogeneous fecal virus
      community compared with viruses in saliva. We measured the relative diversity of
      viruses, and found that the oral viromes were significantly more diverse than
      fecal viromes. There were characteristic changes in the membership of oral and
      fecal bacterial communities in response to antibiotics, but changes in fecal
      viral communities were less distinguishing. In the oral cavity, an abundance of
      papillomaviruses found in subjects on antibiotics suggests an association between
      antibiotics and papillomavirus production. Despite the abundance of
      papillomaviruses identified, in neither the oral nor the fecal viromes did
      antibiotic therapy have any significant impact upon overall viral diversity.
      There was, however, an apparent expansion of the reservoir of genes putatively
      involved in resistance to numerous classes of antibiotics in fecal viromes that
      was not paralleled in oral viromes. The emergence of antibiotic resistance in
      fecal viromes in response to long-term antibiotic therapy in humans suggests that
      viruses play an important role in the resilience of human microbial communities
      to antibiotic disturbances. 

PMID- 26309139
TI  - Sweat chloride concentrations in children with Idiopathic Nephrotic Syndrome.
AB  - BACKGROUND: Idiopathic Nephrotic Syndrome (INS) has been believed to cause a
      false positive elevation of sweat chloride concentrations, as measured by the
      sweat test. METHODS: Sweat tests were done for 11 children with acute onset INS
      at admission and again while they were in remission, with results being compared
      to normal historical controls. RESULTS: The initial sweat chloride concentration
      for 10 patients was normal (mean16.7 +/- 11.02 mmol/L) and 1 patient had
      inadequate collection. This latter patient and two others were excluded during
      follow-up because of diagnoses other than INS. Sweat test results for the eight
      INS patients during follow up remained unchanged when they were in remission
      (16.94 +/- 7.88 mmol/L; P = 0.98; Wilcoxon Matched-Pairs Signed Rank Test). In
      comparing sweat chloride concentrations from INS patients to those from 20
      historical control subjects, we found no significant differences (Mann-Whitney
      Test; initial vs. control P = 0.643; follow up vs. control P = 0.806).
      CONCLUSIONS: INS does not cause a false positive sweat test. Further studies
      should be done to objectively assess the conditions that have been reported to
      affect sweat chloride concentrations.

PMID- 26309138
TI  - A Novel Isoquinoline Derivative Anticancer Agent and Its Targeted Delivery to
      Tumor Cells Using Transferrin-Conjugated Liposomes.
AB  - We have screened 11 isoquinoline derivatives and alpha-methylene-gamma
      butyrolactones using the 3-(4,5-dimethylthi-azol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) cytotoxicity assay in HeLa and HEK-293T cells. Compound 2 was
      identified as potential anticancer agent. To further improve its therapeutic
      potential, this agent was incorporated into transferrin (Tf)-conjugated liposomes
      (LPs) for targeted delivery to tumor cells. We have demonstrated Tf-LP-Compound 2
      have superior antitumor activity compared to non-targeted controls and the free
      drug. These data show Tf-LP-Compound 2 to be a promising agent that warrants
      further evaluation. 

PMID- 26309140
TI  - Body mass index and dermal remodelling.

PMID- 26309141
TI  - Cutaneous Lesions Due to Bites by Larval Amblyomma americanum Ticks.

PMID- 26309143
TI  - Diarylferrocene tweezers for cation binding.
AB  - The host-guest chemistry of ferrocene derivatives was explored by a combined
      experimental and theoretical study. Several 1-arylferrocenes and 1,1'
      diarylferrocenes were synthesized by the Suzuki-Miyaura cross-coupling reaction.
      The ability of these compounds to bind small cations in the gas phase was
      investigated experimentally by electrospray ionization mass spectrometry (ESI
      MS). The results evidenced a noticeable ability of all 1,1'-diarylferrocenes
      studied to bind cations, while the same was not observed for the corresponding 1
      arylferrocenes nor ferrocene. The 1,1'-diarylferrocenecation relative interaction
      energies were evaluated by ESI-MS and quantum chemical calculations and showed
      that cation binding in these systems follows electrostatic trends. It was found
      that, due to their unique molecular shape and smooth torsional potentials, 1,1'
      diarylferrocenes can act as molecular tweezers of small-sized cations in the gas
      phase. 

PMID- 26309142
TI  - Quantitative assessment of vestibular otopathology in otosclerosis: A temporal
      bone study.
AB  - OBJECTIVES/HYPOTHESIS: To determine if peripheral vestibular otopathology is
      present in human temporal bones with otosclerosis. STUDY DESIGN: Comparative
      human temporal bone study. METHODS: Seventy-four human temporal bones from 46
      subjects with otosclerosis (mean age of 61 +/- 18 years) and 20 within
      histologically normal limits from 17 subjects (mean age of 59 +/- 14 years) were
      included in this study. Temporal bones with otosclerosis were divided into those
      with and without endosteal involvement. Using differential interference contrast
      microscopy at 1008* magnification, type I and type II vestibular hair cell counts
      were performed on each vestibular sense organ in which the neuroepithelia was
      oriented perpendicular to the plane of section. The organ-specific cell densities
      (cells/0.01 mm(2) surface area) were compared between the groups with and without
      endosteal involvement, and also compared to counts in the nonotosclerosis control
      group using Student's t-test. RESULTS: Mean type I and type II hair cell
      densities of all vestibular structures in the group with endosteal involvement
      were significantly lower compared to the group without endosteal involvement.
      Mean type I and type II hair cell densities of all vestibular structures in the
      group with endosteal involvement were also significantly lower compared to the
      control group, but they were not in the group without endosteal involvement
      compared to the control group. CONCLUSION: Endosteal involvement of otosclerotic
      foci is associated with vestibular hair cell loss that may contribute to the
      vestibular symptoms in otosclerosis. LEVEL OF EVIDENCE: N/A. Laryngoscope,
      126:E118-E122, 2016.

PMID- 26309144
TI  - Human Papillomavirus vaccination in general practice in France, three years after
      the implementation of a targeted vaccine recommendation based on age and sexual
      history.
AB  - In France, vaccination against human papilloma virus (HPV) was recommended in
      2007 for all 14-year-old girls as well as "catch-up" vaccination for girls
      between 15-23 y of age either before or within one year of becoming sexually
      active. We evaluated the vaccine coverage according to the eligibility for
      vaccination in a sample of young girls aged 14 to 23 years, who were seen in
      general practices. A survey was proposed to 706 general practitioners (GPs) and
      carried out from July to September 2010. GPs, also called "family doctor," are
      physicians whose practice is not restricted to a specific field of medicine but
      instead covers a variety of medical problems in patients of all ages. Each
      participating GP included, retrospectively, the last female patient aged 14-17 y
      and the last female patient aged 18-23 y whom he had seen. A questionnaire
      collected information regarding the GP and the patients' characteristics. The
      vaccine coverage was determined according to the eligibility for vaccination,
      i.e. the coverage among younger women (14-17) and among those sexually active in
      the second age range (18-23). Sexual activity status was assessed by GP,
      according to information stated in the medical record. The 363 participating
      physicians (response rate 51.4%) included 712 patients (357 in the 14- to 17-year
      old group and 355 in the 15- to 23-year-old group) in their responses. The rate
      of the vaccination coverage in the 14- to 17-year-old group was 55%. Among the
      girls in the 18- to 23-year-old group, 126 were eligible, and their vaccination
      coverage rate was 82%. The evaluation of the eligibility by the GPs was incorrect
      in 36% of the cases. Of the 712 patients, 6% of the girls had been vaccinated
      without a need for the vaccination, and 26% of the girls had not been vaccinated,
      although they needed to be vaccinated. Regarding the vaccine uptake, vaccination
      at the age of 14 was not as effective as vaccinating the older population for
      which vaccination was indicated as a catch-up program, based on sexual history.
      However, in more than one-third of the older population, difficulties remained
      regarding the determination of eligibility, according to the sexual history of
      the patient.

PMID- 26309145
TI  - On the Motion of Carbon Nanotube Clusters near Optical Fiber Tips:
      Thermophoresis, Radiative Pressure, and Convection Effects.
AB  - We analyze the motion of multiwalled carbon nanotubes clusters in water or
      ethanol upon irradiation with a 975 and 1550 nm laser beam guided by an optical
      fiber. Upon measuring the velocities of the nanotube clusters in and out of the
      laser beam cone, we were able to identify thermophoresis, convection and
      radiation pressure as the main driving forces that determine the equilibrium
      position of the dispersion at low optical powers: while thermophoresis and
      convection pull the clusters toward the laser beam axis (negative Soret
      coefficient), radiation pressure pushes the clusters away from the fiber tip. A
      theoretical solution for the thermophoretic velocity, which considers interfacial
      motion and a repulsive potential interaction between the nanotubes and the
      solvent (hydrophobic interaction), shows that the main mechanism implicated in
      this type of thermophoresis is the thermal expansion of the fluid, and that the
      clusters migrate to hotter regions with a characteristic thermal diffusion
      coefficient D(T) of 9 * 10(-7) cm(2) K(-1) s(-1). We further show that the
      characteristic length associated with thermophoresis is not that of the nanotube
      clusters size, O(1) MUm, but that corresponding to the microstructure of the
      clusters, O(1) nm. We finally discuss the role of the formation of gas-liquid
      interfaces (microbubbles) at high optical powers on the deposition of carbon
      nanotubes on the optical fiber end faces.

PMID- 26309146
TI  - Epidermal innervation morphometry by immunofluorescence and bright-field
      microscopy.
AB  - We investigated the agreement between simple indirect immunofluorescence (IF) and
      bright-field immunohistochemistry (BFI) on free-floating sections for
      intraepidermal nerve fiber density (IENFD) quantification. Fifty-five healthy
      subjects and 63 patients with probable small fiber neuropathy (SFN) underwent two
      adjacent skin biopsies at the distal leg processed by IF and BFI technique.
      Agreement between IENFD pairs obtained by each method was assessed by Bland
      Altman testing. The area under the curve of the receiving operating
      characteristics (ROC) curves was used to compare the discrimination ability. The
      diagnostic judgment was based on sex and age-adjusted normative values. IF and
      BFI showed good correlation (r = 0.81), with a ratio of about 2:1 and a mean
      difference of 5.5 +/- 3.0 IENF per millimeter between paired measures, as
      demonstrated by linear regression and Bland-Altman test analyses. The square root
      transformation confirmed a Poisson distribution of the data and a fixed bias
      between IF and BFI measurements. The ROC curves analysis demonstrated a striking
      overlap between IF and BFI (0.83 and 0.82; p = 0.72). The diagnosis of SFN
      disagreed in only 6.7% of cases when the judgment was based on a difference of >1
      IENF from 5% cut-off value. IF and BFI showed comparable diagnostic efficiency
      when referred to appropriate normative reference values. 

PMID- 26309147
TI  - The relationship between ethnic-racial socialization and adolescent substance
      use: An examination of social learning as a causal mechanism.
AB  - The presence of parental socialization messages relevant to a child's
      race/ethnicity--ethnic-racial socialization (ERS)--have been found to be an
      important predictor of developmental outcomes. However, scholars have recently
      called for greater theoretical clarification, citing the need for better
      understanding of how the effects of ethnic-racial socialization messages differ
      by dimension and what causal mechanisms underlie this relationship. Using survey
      data from 269 Southern California high school students, this study tested a
      theoretical model examining how 3 dimensions of ERS differentially relate to
      adolescent substance use, and how much these links are mediated by peer substance
      use social learning (Akers, 2009). Using structural equation modeling, we cross
      sectionally and longitudinally tested the pathways between ERS and peer substance
      use social learning and between peer social learning and substance use. We found
      that 2 of the 3 dimensions of ERS were related to substance use. Cultural
      socialization was associated with lower substance use, and promotion of mistrust
      was associated with greater substance use. Both effects were indirect and
      mediated by peer substance use social learning. These results were replicated in
      a separate analysis of the largest ethnic subsample (Latinos). Ethnic-racial
      socialization messages that stress pride in one's ethnic group and the
      development of one's ethnic identity (cultural socialization) may be a protective
      factor against future substance use by inhibiting the association with substance
      using peers, whereas messages that stress distrust of other ethnic groups
      (promotion of mistrust) may be a risk factor against future substance use by
      promoting the association with substance-using peers.

PMID- 26309149
TI  - PET performance and MRI compatibility evaluation of a digital, ToF-capable
      PET/MRI insert equipped with clinical scintillators.
AB  - We evaluate the MR compatibility of the Hyperion-II(D) positron emission
      tomography (PET) insert, which allows simultaneous operation in a clinical
      magnetic resonance imaging (MRI) scanner. In contrast to previous investigations,
      this work aims at the evaluation of a clinical crystal configuration. An imaging
      capable demonstrator with an axial field-of-view of 32 mm and a crystal-to
      crystal spacing of 217.6 mm was equipped with LYSO scintillators with a pitch of
      4 mm which were read out in a one-to-one coupling scheme by sensor tiles composed
      of digital silicon photomultipliers from Philips Digital Photon Counting (DPC
      3200-22). The PET performance degradation (energy resolution and coincidence
      resolution time (CRT)) was evaluated during simultaneous operation of the MRI
      scanner. We used clinically motivated imaging sequences as well as synthetic
      gradient stress test sequences. Without activity of the MRI scanner, we measured
      for trigger scheme 1 (first photon trigger) an energy resolution of 11.4% and a
      CRT of 213 ps for a narrow energy (NE) window using five (22)Na point-like
      sources. When applying the synthetic gradient sequences, we found worst-case
      relative degradations of the energy resolution by 5.1% and of the CRT by 33.9%.
      After identifying the origin of the degradations and implementing a fix to the
      read-out hardware, the same evaluation revealed no degradation of the PET
      performance anymore even when the most demanding gradient stress tests were
      applied. The PET performance of the insert was initially evaluated using the
      point sources, a high-activity phantom and hot-rod phantoms in order to assess
      the spatial resolution. Trigger schemes 2-4 delivered an energy resolution of
      11.4% as well and CRTs of 279 ps, 333 ps and 557 ps for the NE window,
      respectively. An isocenter sensitivity of 0.41% using the NE window and 0.71%
      with a wide energy window was measured. Using a hot-rod phantom, a spatial
      resolution in the order of 2 mm was demonstrated and the benefit of time-of
      flight PET was shown with a larger rabbit-sized phantom. In conclusion, the
      Hyperion architecture is an interesting platform for clinically driven hybrid
      PET/MRI systems. 

PMID- 26309148
TI  - 6-Hydroxy-1,2,4-triazine-3,5(2H,4H)-dione Derivatives as Novel D-Amino Acid
      Oxidase Inhibitors.
AB  - A series of 2-substituted 6-hydroxy-1,2,4-triazine-3,5(2H,4H)-dione derivatives
      were synthesized as inhibitors of D-amino acid oxidase (DAAO). Many compounds in
      this series were found to be potent DAAO inhibitors, with IC50 values in the
      double-digit nanomolar range. The 6-hydroxy-1,2,4-triazine-3,5(2H,4H)-dione
      pharmacophore appears metabolically resistant to O-glucuronidation unlike other
      structurally related DAAO inhibitors. Among them, 6-hydroxy-2-(naphthalen-1
      ylmethyl)-1,2,4-triazine-3,5(2H,4H)-dione 11h was found to be selective over a
      number of targets and orally available in mice. Furthermore, oral
      coadministration of D-serine with 11h enhanced the plasma levels of D-serine in
      mice compared to the oral administration of D-serine alone, demonstrating its
      ability to serve as a pharmacoenhancer of D-serine.

PMID- 26309150
TI  - Ligand Control of Manganese Telluride Molecular Cluster Core Nuclearity.
AB  - We report the synthesis, structural diversity, and chemical behavior of a family
      of manganese telluride molecular clusters whose charge-neutral cores are
      passivated by two-electron donor ligands. We describe three different core
      structures: a cubane-type Mn4Te4, a prismane Mn6Te6, and a dicubane Mn8Te8. We
      use various trialkylphosphines and N-heterocyclic carbenes (NHCs) as surface
      ligands and demonstrate that the formation of the different cluster core
      structures is controlled by the choice of ligand: bulky ligands such as P(i)Pr3,
      PCy3, or (i)Pr2NHC ((i)Pr2NHC = 1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene)
      form the cubane-type core, while the smaller PMe3 produces the prismane core. The
      intermediate-sized PEt3 produces both cubane and prismane species. These
      manganese telluride molecular clusters are labile, and the capping phosphines can
      be replaced by stronger ligands, while the internal core structure of the cluster
      remains intact. The interplay of structural diversity and ligand versatility and
      lability makes these clusters potentially useful building blocks for the assembly
      of larger aggregates and extended structures. We demonstrate the simplest
      prototype of these solid-forming reactions: the direct coupling of two
      Mn4Te4((i)Pr2NHC)4 units to form the dicubane Mn8Te8((i)Pr2NHC)6. We also
      postulate the prismatic Mn6Te6 as the common ancestor of both Chevrel-type M6E8
      and octanuclear rhombododecahedral M8E6 molecular clusters (M = transition metal
      and E = chalcogen), and we discuss the core structure of our molecular clusters
      as recognizable building units for the zinc blende and the hypothetical wurtzite
      lattices of MnTe. 

PMID- 26309151
TI  - Exploiting hydrophobicity for efficient production of transmembrane helices for
      structure determination by NMR spectroscopy.
AB  - Despite the biological and pharmaceutical significance of membrane proteins,
      their tertiary structures constitute less than 3% of known structures. One of the
      major obstacles for initiating structural studies of membrane proteins by NMR
      spectroscopy is the generation of high amounts of isotope-labeled protein. In
      this work, we have exploited the hydrophobic nature of membrane proteins to
      develop a simple and efficient production scheme for isotope-labeled single-pass
      transmembrane domains (TMDs) with or without intrinsically disordered regions. We
      have evaluated the applicability and limitations of the strategy using seven
      membrane protein variants that differ in their overall hydrophobicity and length
      and show a recovery for suitable variants of >70%. The developed production
      scheme is cost-efficient and easy to implement and has the potential to
      facilitate an increase in the number of structures of single-pass TMDs, which are
      difficult to solve by other means. 

PMID- 26309152
TI  - PIP2 and Talin Join Forces to Activate Integrin.
AB  - Integrins are major players in cell adhesion and migration, and malfunctions in
      controlling their activity are associated with various diseases. Nevertheless,
      the details of integrin activation are not completely understood, and the role of
      lipids in the process is largely unknown. Herein, we show using atomistic
      molecular dynamics simulations that the interplay of phosphatidylinositol 4,5
      bisphosphate (PIP2) and talin may directly alter the conformation of integrin
      alphaIIbbeta3. Our results provide a new perspective on the role of PIP2 in
      integrin activation and indicate that the charged PIP2 lipid headgroup can
      perturb a clasp at the cytoplasmic face of the integrin heterodimer. 

PMID- 26309153
TI  - Profiling the Hydrolysis of Isolated Grape Berry Skin Cell Walls by Purified
      Enzymes.
AB  - The unraveling of crushed grapes by maceration enzymes during winemaking is
      difficult to study because of the complex and rather undefined nature of both the
      substrate and the enzyme preparations. In this study we simplified both the
      substrate, by using isolated grape skin cell walls, and the enzyme preparations,
      by using purified enzymes in buffered conditions, to carefully follow the impact
      of the individual and combined enzymes on the grape skin cell walls. By using
      cell wall profiling techniques we could monitor the compositional changes in the
      grape cell wall polymers due to enzyme activity. Extensive enzymatic hydrolysis,
      achieved with a preparation of pectinases or pectinases combined with cellulase
      or hemicellulase enzymes, completely removed or drastically reduced levels of
      pectin polymers, whereas less extensive hydrolysis only opened up the cell wall
      structure and allowed extraction of polymers from within the cell wall layers.
      Synergistic enzyme activity was detectable as well as indications of specific
      cell wall polymer associations. 

PMID- 26309154
TI  - Biophysical and molecular docking insight into interaction mechanism and thermal
      stability of human serum albumin isoforms with a semi-synthetic water-soluble
      camptothecin analog irinotecan hydrochloride.
AB  - In the present work, we have examined the binding parameters, thermodynamics, and
      stability of human serum albumin (HSA) isoforms at pH 7.4 and 9.0, using
      spectroscopic, calorimetric, and molecular docking methods in the presence of
      water-soluble camptothecin analog irinotecan hydrochloride (CPT-11). We observed
      that CPT-11 binds to HSA through a static quenching procedure of ground-state
      complex formation with N-isoform and B-isoform. Hydrogen bond and hydrophobic
      interactions are the major governing forces that participating in the formation
      of protein-drug complex. To determine the binding site of CPT-11 within HSA
      molecules, we also have performed molecular docking experiments. We explored the
      CPT-11-mediated stability and modulation of HSA by performing dynamic light
      scattering (DLS) and differential scanning calorimetry (DSC) experiments. DLS and
      DSC techniques are used to determine the size and the melting point (Tm) of HSA,
      which was decreased in the presence of CPT-11. Therefore, CPT-11 plays an
      important role in HSA stability and protein-ligand interactions. The present
      study provides valuable information in the field of pharmacokinetics, pharmaco
      dynamics, and drug discovery. 

PMID- 26309155
TI  - Surgeon-Therapist Communication: Do All Members See Eye-to-Eye?
AB  - BACKGROUND: Poor interprofessional collaboration has been shown to negatively
      affect patient care within many fields of medicine. Growing evidence is
      suggesting that improved interprofessional collaboration can positively affect
      patient care. Postoperative rehabilitation of many orthopedic conditions
      necessitates the combined efforts of surgeons, and therapists. There is a paucity
      of literature examining collaboration among orthopedic surgeons and therapists
      regarding postoperative rehabilitation. OBJECTIVES: The following study examines
      the perceived quality of communications between orthopedic surgeons and
      therapists employing an online survey. We hypothesized that collaborative
      practice patterns result in improved perceptions of communication. METHODS:
      Ethics board approval was obtained. Subjects consisted of orthopedic surgeons,
      licensed physiotherapists and certified athletic therapists. The online survey
      was distributed through the Canadian Orthopaedic Association (COA), the Canadian
      Physiotherapy Association (CPA) and the Canadian Athletic Therapists Association
      (CATA). Data analysis was performed using Stata/IC 12.1 (Stata Corp, College
      Station, TX, USA). Descriptive statistics were calculated to determine the median
      responses and ranges. Median responses were compared using the Kruskal-Wallis one
      way analysis of variance. Qualitative analysis regarding text responses was
      performed by three reviewers. RESULTS: Responses were received from all
      specialties (COA 164, CPA 524, CATA 163). There were significant differences in
      the perceived quality of communication by quantitative and qualitative analysis
      (p < 0.001). Analysis of communication within practice patterns of stand-alone
      versus collaborative revealed improved perception of communication quality with
      increased contact. 65.6% of responders that practiced as stand-alone had a
      negative view of interprofessional communication. 48.4% of responders in a
      collaborative practice had a positive view of interprofessional communication.
      Analysis of the preferred form of communication found that orthopedic surgeons
      felt the most useful referral information was a pre-printed consult sheet (odds
      ratio [OR] = 1.56, p < 0.001), whereas therapists were more likely to rank
      consult notes (OR = 1.27, p < 0.042) and operative reports (OR = 1.20, p < 0.092)
      as a more useful form of communication. CONCLUSIONS: Collaborative practice shows
      improved perceptions of communication between specialties. Orthopedic surgeons
      perceive a higher quality of communication than therapists. Therapists and
      orthopedic surgeons also do not agree on the information that should be relayed
      between the specialties regarding postoperative rehabilitation.

PMID- 26309156
TI  - Synthesis, antioxidant and carbonic anhydrase I and II inhibitory activities of
      novel sulphonamide-substituted coumarylthiazole derivatives.
AB  - New secondary benzenesulphonamide-substituted coumarylthiazole derivatives were
      synthesized and their inhibitory effects on purified carbonic anhydrase I and II
      were evaluated using CO2 as a substrate. The result showed that all the
      synthesized compounds exhibited inhibitory activity on both hCA I and hCA II with
      N-(4-(2-oxo-2H-chromen-3-yl)thiazol-2-yl)naphthalene-2-sulphonamide (5f, IC50
      value of 5.63 and 8.48 uM, against hCA I and hCA II, respectively) as the
      strongest inhibitor revealed from this study. Structure-activity relationship
      revealed that the inhibitory activity of the synthesized compounds is related to
      the type of the halogen and bulky substituent on the phenyl ring. In addition,
      the cupric reducing antioxidant capacities (CUPRAC) and ABTS cation radical
      scavenging abilities of the synthesized compounds were assayed. 4-methoxy-N-(4-(2
      oxo-2H-chromen-3-yl)thiazol-2-yl)benzenesulphonamide (5e) exhibited the strongest
      ABTS and CUPRAC activity with IC50 value of 48.83 uM and A0.50 value of 23.29 uM,
      respectively. 

PMID- 26309157
TI  - Ag(I)-Catalyzed Three-Component Reaction of 2-Alkynylbenzaldehydes, Amines, and
      Diazo Compounds.
AB  - Diazo compounds have been employed as the nucleophile in a silver-catalyzed three
      component reaction with amines and 2-alkynylbenzaldehydes. Various 3-benzazepines
      were prepared in a one-pot manner based on a cascade imine--yne
      cyclization/nucleophilic addition/1,2-aryl migration process. Moreover, this
      Ag(I)-mediated reaction also provides a practical route to diazo-containing
      dihydroisoquinolines under slightly modified conditions. 

PMID- 26309158
TI  - Pd-Catalyzed Stereoselective Carboperfluoroalkylation of Alkynes.
AB  - A Pd-catalyzed three component reaction involving terminal alkynes, boronic
      acids, and perfluoroalkyl iodides is presented here. Trisubstituted
      perfluoroalkenes can be obtained in a highly regio- and stereocontrolled manner
      by the simultaneous addition of both aryl and CnFm groups across the triple bond
      in a radical-mediated process. The reaction is operationally simple offering a
      broad scope and functional group tolerance. 

PMID- 26309159
TI  - ERRATUM.

PMID- 26309160
TI  - Identification of GALNT14 as a novel neuroblastoma predisposition gene.
AB  - Although several genes have been associated to neuroblastoma (NB) predisposition
      and aggressiveness, further genes are likely involved in the overall risk of
      developing this pediatric cancer. We thus carried out whole-exome sequencing on
      germline DNA from two affected second cousins and two unlinked healthy relatives
      from a large family with hereditary NB. Bioinformatics analysis revealed 6999
      variations that were exclusively shared by the two familial NB cases. We then
      considered for further analysis all unknown or rare missense mutations, which
      involved 30 genes. Validation and analysis of these variants led to identify a
      GALNT14 mutation (c.802C > T) that properly segregated in the family and was
      predicted as functionally damaging by PolyPhen2 and SIFT. Screening of 8
      additional NB families and 167 sporadic cases revealed this GALNT14 mutation in
      the tumors of two twins and in the germline of one sporadic NB patient. Moreover,
      a significant association between MYCN amplification and GALNT14 expression was
      observed in both NB patients and cell lines. Also, GALNT14 higher expression is
      associated with a worse OS in a public dataset of 88 NB samples
      (http://r2.amc.nl). GALNT14 is a member of the polypeptide N-acetylgalactosaminyl
      transferase family and maps closely to ALK on 2p23.1, a region we previously
      discovered in linkage with NB in the family here considered. The aberrant
      function of GALNTs can result in altered glycoproteins that have been associated
      to the promotion of tumor aggressiveness in various cancers. Although rare, the
      recurrence of this mutation suggests GALNT14 as a novel gene potentially involved
      in NB predisposition. 

PMID- 26309161
TI  - The oncoprotein HBXIP promotes glucose metabolism reprogramming via
      downregulating SCO2 and PDHA1 in breast cancer.
AB  - The glucose metabolism reprogramming is a hallmark of cancer. The oncoprotein
      hepatitis B X-interacting protein (HBXIP) functions in the development of breast
      cancer. In this study, we supposed that HBXIP might be involved in the glucose
      metabolism reprogramming in breast cancer. We showed that HBXIP led to increases
      in generation of intracellular glucose and lactate, as well as decreases in
      generation of reactive oxygen species. Expression of synthesis of cytochrome c
      oxidase 2 (SCO2) and pyruvate dehydrogenase alpha 1 (PDHA1), two factors of
      metabolic switch from oxidative phosphorylation to aerobic glycolysis, was
      suppressed by HBXIP. In addition, miR-183/182 and miR-96 directly inhibited the
      expression of SCO2 and PDHA1 through targeting their mRNA coding sequences
      (CDSs), respectively. Interestingly, HBXIP elevated the miR-183/96/182 cluster
      expression through hypoxia-inducible factor 1alpha (HIF1alpha). The stability of
      HIF1alpha was enhanced by HBXIP through disassociating interaction of von Hippel
      Lindau protein (pVHL) with HIF1alpha. Moreover, miR-183 increased the levels of
      HIF1alpha protein through directly targeting CDS of VHL mRNA, forming a feedback
      loop of HIF1alpha/miR-183/pVHL/HIF1alpha. In function, HBXIP-elevated miR
      183/96/182 cluster enhanced the glucose metabolism reprogramming in vitro. HBXIP
      triggered glucose metabolism reprogramming promoted the growth of breast cancer
      in vivo. Thus, we conclude that the oncoprotein HBXIP enhances glucose metabolism
      reprogramming through suppressing SCO2 and PDHA1 in breast cancer. 

PMID- 26309162
TI  - Enhanced transfection efficiency and targeted delivery of self-assembling h-R3
      dendriplexes in EGFR-overexpressing tumor cells.
AB  - The efficient gene transfection, cellular uptake and targeted delivery in vivo
      are key issues for non-viral gene delivery vectors in cancer therapy. To solve
      these issues, we designed a new targeted gene delivery system based on epidermal
      growth factor receptor (EGFR) targeting strategy. An anti-EGFR monoclonal
      antibody h-R3 was introduced to dendriplexes of PAMAM and DNA via electrostatic
      interactions to form self-assembled h-R3-PAMAM-DNA complexes (h-R3-dendriplexes).
      Dendriplexes h-R3-dendriplexes represented excellent DNA encapsulation ability
      and formed unique nanostructures. Compared to dendriplexes, h-R3-dendriplexes
      presented lower cytotoxicity, higher gene transfection efficiency, excellent
      endosome escape ability and high nuclear accumulation in the EGFR-overexpressing
      HepG2 cells. Both ex vivo fluorescence imaging and confocal results of frozen
      section revealed that h-R3-dendriplexes showed higher targeted delivery and much
      better gene expression in the tumors than dendriplexes at the same N/P ratio, and
      h-R3-dendriplexes had accumulation primarily in the tumor and kidney. Moreover, h
      R3-dendriplexes for p53 delivery indicated efficient cell growth inhibition and
      potentiated paclitaxel-induced cell death. These results indicate that the h-R3
      dendriplexes represent a great potential to be used as efficient targeted gene
      delivery carriers in EGFR-overexpressing tumor cells. 

PMID- 26309163
TI  - Extramural depth of rectal cancer tumor invasion at thin-section MRI: predicting
      treatment response to neoadjuvant chemoradiation.
AB  - OBJECTIVES: To assess whether the maximal extramural depth (EMD) of T3 tumor
      spread on magnetic resonance imaging(MRI) correlates with tumor response
      parameters and whether it can predict tumor response to neoadjuvant
      chemoradiation. METHODS: 111 rectal cancer patients with American Joint Committee
      on Cancer (AJCC) T3 tumors underwent MRI staging before neoadjuvant
      chemoradiotherapy were included. Tumor EMD was measured as mm tumor beyond the
      muscular and compared between the following groups by Kruskal-Wallis test:
      pathological complete response(pCR) versus nonpCR, good regression versus poor
      regression, downstage versus nondownstage. RESULTS: The final study population
      consisted of the 111 patients (79 male, 32 female). Median age was 56 years
      (range, 23-75 years). The EMD was significantly higher in nonpCR patients (7.8 +/
      3.2 mm) than in pCR patients(6.1 +/- 1.8 mm) (p = 0.033). According to good
      regression (tumor regression grade(TRG) 0-1 vs. TRG 2-3) and downstaging (ypStage
      0-I vs. ypStage II-III), the difference was not significant. Receiver operating
      characteristic curve analysis revealed a good value for the area under the curve
      (0.775) and the cutoff value for EMD to predict pCR was 5.6 mm. Compared with
      patients with a EMD >= 5 mm, more patients with EMD <5 mm showed pCR (p = 0.019),
      while there was no correlation between EMD and good regression or downstaged.
      CONCLUSIONS: EMD value obtained on initial staging MRI may serve as an imaging
      biomarker which predicts patients that have an incomplete response pathological
      response after standard neoadjuvant therapy.

PMID- 26309164
TI  - 89Zr-cetuximab PET imaging in patients with advanced colorectal cancer.
AB  - Monoclonal antibodies (mAbs) against the epidermal growth factor receptor (EGFR)
      are used in the treatment of advanced colorectal cancer (mCRC). Approximately 50%
      of patients benefit despite patient selection for RAS wild type (wt) tumors.
      Based on the hypothesis that tumor targeting is required for clinical benefit of
      anti-EGFR treatment, biodistribution and tumor uptake of (89)Zr-cetuximab by
      Positron Emission Tomography (PET), combining the sensitivity of PET with the
      specificity of cetuximab for EGFR was evaluated. Ten patients with wt K-RAS mCRC
      received 37 +/- 1 MBq (89)Zr-cetuximab directly (<2 h) after the first
      therapeutic dose of cetuximab. PET-scans were performed from 1 hour to 10 days
      post injection (p.i.). Biodistribution was determined for blood and organs.
      Uptake in tumor lesions was quantified by Standardized Uptake Value (SUV) and
      related to response. In 6 of 10 patients (89)Zr-cetuximab uptake in tumor lesions
      was detected. Four of 6 patients with (89)Zr-cetuximab uptake had clinical
      benefit, while progressive disease was observed in 3 of 4 patients without (89)Zr
      cetuximab uptake. Taken together, tumor uptake of 89Zr-cetuximab can be
      visualized by PET imaging. The strong relation between uptake and response
      warrants further clinical validation as an innovative selection method for
      cetuximab treatment in patients with wt RAS mCRC.

PMID- 26309166
TI  - Thoughts on Bringing Back the Asylum.

PMID- 26309165
TI  - Attention training normalises combat-related post-traumatic stress disorder
      effects on emotional Stroop performance using lexically matched word lists.
AB  - We examined two groups of combat veterans, one with post-traumatic stress
      disorder (PTSD) (n = 27) and another without PTSD (n = 16), using an emotional
      Stroop task (EST) with word lists matched across a series of lexical variables
      (e.g. length, frequency, neighbourhood size, etc.). Participants with PTSD
      exhibited a strong EST effect (longer colour-naming latencies for combat-relevant
      words as compared to neutral words). Veterans without PTSD produced no such
      effect, t < .918, p > .37. Participants with PTSD then completed eight sessions
      of attention training (Attention Control Training or Attention Bias Modification
      Training) with a dot-probe task utilising threatening and neutral faces. After
      training, participants-especially those undergoing Attention Control Training-no
      longer produced longer colour-naming latencies for combat-related words as
      compared to other words, indicating normalised attention allocation processes
      after treatment.

PMID- 26309167
TI  - Balancing Risk: A Grounded Theory Study of Pregnant Women's Decisions to
      (Dis)Continue Antidepressant Therapy.
AB  - This study explored how eight pregnant women diagnosed with depression managed
      the decision whether or not to take antidepressants during pregnancy. In total,
      11 interviews were conducted and analysed by means of constructivist grounded
      theory. The major category constructed was Balancing risk, with two minor
      categories: Assessing depression and antidepressants and Evaluating the impact of
      significant others. The participants tried to make the safest decision, taking
      all aspects of their life into consideration. They described successful decision
      making in the context of managing social norms that surround pregnancy, in a way
      that was acceptable to themselves, their significant others and healthcare
      professionals. 

PMID- 26309168
TI  - Health Behavior Decision-making in African-American Adults Diagnosed with
      Schizophrenia.
AB  - Little is known about the factors that influence health behavior decision-making
      among people with schizophrenia. The purpose of this qualitative study was to
      describe the processes used by 10 African-American adults with schizophrenia when
      making health behavior decisions and identification of perceived barriers and
      facilitators to health. Three phases of health behavior decision-making were
      identified: Recognizing Complex Components of Health, Personalizing Components of
      Health, and Tracking Health Status. Findings may guide clinicians' efforts to
      improve the health status of patients, as well as influence future research in
      understanding health behavior decision-making among vulnerable populations. 

PMID- 26309169
TI  - Simulation in Nursing Education: iPod As a Teaching Tool for Undergraduate
      Nurses.
AB  - Most people with psychosis and schizophrenia experience auditory hallucinations,
      particularly the hearing of voices. A common cause of frustration and alienation
      for consumers is the lack of understanding by therapists, family members and
      caregivers, who find it difficult to relate to the consumers' experiences. The
      purpose of this study is to examine and evaluate whether students' participation
      in a simulated auditory hallucination will increase their understanding and
      knowledge about psychosis and auditory hallucinations. The design method
      consisted of a lecture on psychosis and schizophrenia disorders, followed by a
      simulation of auditory hallucinations using iPods. Students' knowledge and
      perceptions of psychosis and hallucinations was assessed using quasi-experimental
      pre-post matched-design questionnaires. The questionnaire was divided into two
      parts, the first comprised closed questions to assess students' knowledge, and
      the second part consisted of open-ended questions to collect information about
      students' perceptions of auditory hallucinations. The results confirmed that
      students' knowledge of psychosis and hallucination increased following the
      teaching session and simulation is a useful tool to prepare students for clinical
      placements in mental health practice. 

PMID- 26309170
TI  - Good Practices For Infection Prevention and Control at a Psychiatric Hospital in
      Brazil.
AB  - This exploratory cross-sectional study aims to investigate good practice for
      preventing and controlling infections in a psychiatric hospital and for limiting
      potential exposure to biohazards for nursing professionals at this hospital
      located in the State of Sao Paulo, Brazil. The researchers directly and
      systematically observed 830 nursing procedures, 40.6% of which presented a
      moderate to high risk of biohazard exposure. Results indicate very low adherence
      to hand hygiene (1.2% before procedures, 2.9% after procedures), inappropriate
      use of gloves, and other instances of noncompliance to the standards of good
      practice for preventing and controlling infection, such as a lack of
      concurrent/terminal cleaning of dirty beds (132 instances) and careless
      manipulation of sharp devices (34 instances). 

PMID- 26309172
TI  - Staff Burnout--a Comparative Study of Metropolitan and Rural Mental Health Nurses
      within Australia.
AB  - This article will present the findings of a research study that investigated the
      extent to which mental health nurses employed within rural and metropolitan areas
      of Australia are affected by burnout, using the Maslach Burnout Inventory (MBI)
      and a demographic questionnaire. The study also examined whether the Maslach
      Burnout Inventory (MBI) was a valid measure of mental health burnout within the
      Australian context and culture or alternatively, in what ways it needed to be
      refined? A cross-sectional study of mental health nurses (n  =  319) from the
      states of New South Wales, Victoria, Queensland and Western Australia was
      undertaken. The 22-item Maslach Burnout Inventory (MBI) was used to measure
      burnout and a demographic questionnaire utilising a cluster sampling, cross
      sectional design survey method, was used to gather the data. The study found that
      gender and level of qualification were the two major factors that showed any
      significance, where males experienced a higher level of depersonalisation on the
      frequency and intensity sub-scale scores of the MBI and that the more qualified a
      nurse, the greater the level of depersonalisation they experienced. These results
      were true for participants in both rural and metropolitan settings within
      Australia. Age was the third most influencing factor in terms of emotional
      exhaustion, where younger participants (under 30) reported higher levels of
      emotional exhaustion. Younger male mental health nurses experienced higher levels
      of depersonalisation. 

PMID- 26309171
TI  - Factors Related to Depressive Symptoms in Mothers of Technology-Dependent
      Children.
AB  - Mothers caring for technology-dependent children at home often suffer clinically
      significant and unrecognized depressive symptoms. The study aim was to determine
      factors related to elevated depressive symptoms and provide information to target
      interventions that assists mothers in self-management of their mental health.
      Secondary data analysis from a descriptive, correlational study of 75 mothers was
      performed. Hierarchical multiple regression analysis results indicate that
      younger, unpartnered mothers with lower normalization efforts and personal
      resourcefulness, and less care hours, had increased depressive symptoms. The
      importance of personal resourcefulness and the potential for a resourcefulness
      training intervention to reduce depressive symptoms are discussed. 

PMID- 26309173
TI  - Motivational Factors that Help in Coping with Barriers to Provision of
      Psychiatric Nursing Care: Perspective of Psychiatric Nurses in a Hospital Setting
      in Nigeria.
AB  - This qualitative case study explored barriers to provision of psychiatric nursing
      care in a hospital in Plateau State, Nigeria, and revealed motivational factors
      that helped the nurses to cope with these barriers. Data collection methods
      included grand tour and in-depth interviews and participant observation.
      Motivational factors were related to the psychiatric nurse's individual intrinsic
      belief system, as well as to their intrinsic belief system as influenced by the
      environment. These motivational factors highlight how psychiatric nurses continue
      to cope with the barriers they face in provision of care. The findings indicate
      the need for hospital management to create and sustain an environment to
      complement the existing intrinsic motivation of psychiatric nurses to provide
      psychiatric nursing care, and to provide prompt and appropriate emotional and
      psychological support to psychiatric nurses worldwide. 

PMID- 26309174
TI  - Hovering between Heaven and Hell: An Observational Study Focusing on the
      Interactions between One Woman with Schizophrenia, Dementia, and Challenging
      Behaviour and her Care Providers.
AB  - This case study aims to illuminate the interactions between one woman (Alice)
      with schizophrenia, dementia, and challenging behaviour and her professional
      caregivers. We performed participant observations of these interactions and
      conducted informal interviews at the residential home where the woman lived. The
      transcripts were subjected to qualitative content analysis. The results showed
      that the interactions between Alice and her caregivers were experienced as
      hovering between heaven and hell. Alice struggled to bring order into her chaotic
      life world by splitting herself and others, and her caregivers struggled to
      protect Alice's and their own dignity by limiting her challenging behaviours.
      They also strived to understand their own and Alice's behaviour. Current practice
      in caring for people with challenging behaviour usually focuses on symptom
      reduction through medication and behavioural modification. Instead, we suggest
      moving toward an understanding of the experiences behind the challenging
      behaviours and designing person-centred care based on each patients' reality. 

PMID- 26309175
TI  - The Therapeutic Relationship in the Shadow: Nurses' Experiences of Barriers to
      the Nurse-Patient Relationship in the Psychiatric Ward.
AB  - The therapeutic relationship is widely accepted as the basic core and essence of
      the psychiatric nurse's role and is thus essential for providing quality mental
      health care. A detailed and clear perception of the issues that facilitate or
      obstruct this relationship is therefore important. The purpose of this study was
      to gain insights into the experiences of nurses working in psychiatry wards, of
      the barriers to the nurse-patient relationship. A qualitative content-analysis
      study was undertaken using a purpose-based sampling approach with the
      participation of 15 nurses employed in psychiatric wards in hospitals located in
      South Iran. Semi-structured interviews provided the source of data, and an
      inductive content-analysis approach was used for data analysis. The main concept
      extracted from the study was identified as 'the therapeutic relationship in the
      shadow', which captured the sense that this critical relationship is mostly
      unseen in the daily practice of the nurses interviewed. Factors that functioned
      as barriers to this relationship were classified into three main categories:
      nurse-related, patient-related and organization-related. The results of this
      study revealed that, despite the widely claimed importance of the nurse-patient
      relationship in psychiatric settings, this relationship is powerfully influenced
      by individual and organizational factors that have not been considered adequately
      in previous research. It is strongly recommended that greater consideration of
      these factors be given to care planning in psychiatric wards. 

PMID- 26309176
TI  - Nourishing Mind and Brain.

PMID- 26309177
TI  - Compassion and Mental Health Nursing.

PMID- 26309179
TI  - Risk Denial and Socio-Economic Factors Related to High HIV Transmission in a
      Fishing Community in Rakai, Uganda: A Qualitative Study.
AB  - BACKGROUND: In Kasensero fishing community, home of the first recorded case of
      HIV in Uganda, HIV transmission is still very high with an incidence of 4.3 and
      3.1 per 100 person-years in women and men, respectively, and an HIV prevalence of
      44%, reaching up to 74% among female sex workers. We explored drivers for the
      high HIV transmission at Kasensero from the perspective of fishermen and other
      community members to inform future policy and preventive interventions. METHODS:
      20 in-depth interviews including both HIV positive and HIV negative respondents,
      and 12 focus-group discussions involving a total of 92 respondents from the
      Kasensero fishing community were conducted during April-September 2014. Content
      analysis was performed to identify recurrent themes. RESULTS: The socio-economic
      risk factors for high HIV transmission in Kasensero fishing community cited were
      multiple and cross-cutting and categorized into the following themes: power of
      money, risk denial, environmental triggers and a predisposing lifestyle and
      alcoholism and drug abuse. Others were: peer pressure, poor housing and the
      search for financial support for both the men and women which made them
      vulnerable to HIV exposure and or risk behavior. CONCLUSIONS: There is a need for
      context specific combination prevention interventions in Kasensero that includes
      the fisher folk and other influential community leaders. Such groups could be
      empowered with the knowledge and social mobilization skills to fight the negative
      and risky behaviors, perceptions, beliefs, misconceptions and submission
      attitudes to fate that exposes the community to high HIV transmission. There is
      also need for government/partners to ensure effective policy implementation, life
      jackets for all fishermen, improve the poor housing at the community so as to
      reduce overcrowding and other housing related predispositions to high HIV rates
      at the community. Work place AIDS-competence teams have been successfully used to
      address high HIV transmission in similar settings.

PMID- 26309180
TI  - Bladder Pressure Measurements in Patients Admitted to a Medical Intensive Care
      Unit.
AB  - BACKGROUND: Intra-abdominal hypertension is identified as an independent risk
      factor for death. However, this pathophysiological state is not always considered
      in patients in medical intensive care units and is frequently underdiagnosed.
      METHODS: Serial bladder pressure measurements were recorded in patients admitted
      to the medical intensive care units to determine the frequency of intra-abdominal
      hypertension. RESULTS: This study included 53 patients with a mean age of 59.0 +/
      17.7 years. The average admission intra-abdominal pressure was 10.0 +/- 5.4 mm
      Hg with a range of 0 to 28 mm Hg. Eleven patients (21%) had an initial pressure
      reading above normal (>12 mm Hg). Peak airway pressures were higher, and
      PaO2/FiO2 ratios were lower in patients with an initial pressure >12 mm Hg.
      CONCLUSIONS: Bladder pressure measurements provide an easy method to estimate
      intra-abdominal pressures and provide an additional tool for the physiologic
      assessment of critically ill patients.

PMID- 26309182
TI  - Reply: To PMID 25458910.

PMID- 26309183
TI  - Time-Resolved Analysis of Left Ventricular Shear Wave Amplitudes in Cardiac
      Elastography for the Diagnosis of Diastolic Dysfunction.
AB  - OBJECTIVES: The aim of this study was to investigate the diagnostic potential of
      changes in left ventricular (LV) shear wave amplitudes (SWAs) over the cardiac
      cycle measured by cardiac magnetic resonance elastography. MATERIALS AND METHODS:
      Electrocardiography-triggered SWA-based cardiac magnetic resonance elastography
      with 24.13-Hz external vibration frequency was performed in asymptomatic young (n
      = 10) and old (n = 10) subjects and patients (n = 30) with echocardiographically
      proven mild, moderate, or severe diastolic dysfunction. The temporal delay
      between change in SWA and morphological change in the LV wall, that is, time of
      isovolumetric elasticity relaxation normalized against heart rate, was calculated
      for diastole (tauR0). Diastolic levels of LV SWA were calculated and normalized
      against SWA in the chest wall (U0[dia]). Nonparametric testing was used for
      statistical evaluation. Accuracy of the parameters was investigated using
      receiver operating characteristic analysis against echocardiography.
      Interobserver and intraobserver variability for the temporal delay between change
      in SWA and morphological changes was tested according to Bland and Altman.
      RESULTS: Young and old control subjects showed median (standard error of mean,
      interquartile range) tauR0 of 99 (5, 93-103) and 82 (7, 66-95). In patients with
      diastolic dysfunction, tauR0 was 131 (20, 107-171), 158 (14, 108-172), and 138
      (14, 107-174) with statistically significant differences between old subjects and
      patients with diastolic dysfunction (P = 0.01). U0(dia) was 0.94 (0.05, 0.86
      1.04) and 0.71 (0.06, 0.61-0.92) in young and old controls, respectively (P =
      0.063). Compared with young subjects, patients with mild, moderate, and severe
      diastolic dysfunction displayed significantly reduced U0(dia) of 0.69 (0.06, 0.53
      0.82), 0.56 (0.04, 0.46-0.64), and 0.48 (0.04, 0.43-0.61) (P < 0.001).
      tauR0/U0(dia) cutoff values for prediction of diastolic dysfunction were
      107/0.66, corresponding to the area under the receiver operating characteristic
      values of 0.84/0.87 with 74%/74% sensitivity and 85%/85% specificity.
      Interobserver and intraobserver variability ranged from -0.05 to 0.05 with 95%
      agreement. CONCLUSIONS: In diastolic dysfunction, low-frequency SWAs show
      distinct changes in the normalized time of isovolumetric elasticity relaxation
      for the LV (tauR0) and the diastolic level of SWA (U0[dia]). Both parameters have
      good diagnostic performance for diagnosis of diastolic dysfunction.

PMID- 26309181
TI  - Human B-cell isotype switching origins of IgE.
AB  - BACKGROUND: B cells expressing IgE contribute to immunity against parasites and
      venoms and are the source of antigen specificity in allergic patients, yet the
      developmental pathways producing these B cells in human subjects remain a subject
      of debate. Much of our knowledge of IgE lineage development derives from model
      studies in mice rather than from human subjects. OBJECTIVE: We evaluate models
      for isotype switching to IgE in human subjects using immunoglobulin heavy chain
      (IGH) mutational lineage data. METHODS: We analyzed IGH repertoires in 9 allergic
      and 24 healthy adults using high-throughput DNA sequencing of 15,843,270 IGH
      rearrangements to identify clonal lineages of B cells containing members
      expressing IgE. Somatic mutations in IGH inherited from common ancestors within
      the clonal lineage are used to infer the relationships between B cells. RESULTS:
      Data from 613,641 multi-isotype B-cell clonal lineages, of which 592 include an
      IgE member, are consistent with indirect switching to IgE from IgG- or IgA
      expressing lineage members in human subjects. We also find that these inferred
      isotype switching frequencies are similar in healthy and allergic subjects.
      CONCLUSIONS: We found evidence that secondary isotype switching of mutated IgG1
      expressing B cells is the primary source of IgE in human subjects, with lesser
      contributions from precursors expressing other switched isotypes and rarely IgM
      or IgD, suggesting that IgE is derived from previously antigen-experienced B
      cells rather than naive B cells that typically express low-affinity unmutated
      antibodies. These data provide a basis from which to evaluate allergen-specific
      human antibody repertoires in healthy and diseased subjects.

PMID- 26309184
TI  - Screening Magnetic Resonance Imaging-Based Prediction Model for Assessing
      Immediate Therapeutic Response to Magnetic Resonance Imaging-Guided High
      Intensity Focused Ultrasound Ablation of Uterine Fibroids.
AB  - OBJECTIVES: The aim of this study was to fit and validate screening magnetic
      resonance imaging (MRI)-based prediction models for assessing immediate
      therapeutic responses of uterine fibroids to MRI-guided high-intensity focused
      ultrasound (MR-HIFU) ablation. MATERIALS AND METHODS: Informed consent from all
      subjects was obtained for our institutional review board-approved study. A total
      of 240 symptomatic uterine fibroids (mean diameter, 6.9 cm) in 152 women (mean
      age, 43.3 years) treated with MR-HIFU ablation were retrospectively analyzed (160
      fibroids for training, 80 fibroids for validation). Screening MRI parameters
      (subcutaneous fat thickness [mm], x1; relative peak enhancement [%] in
      semiquantitative perfusion MRI, x2; T2 signal intensity ratio of fibroid to
      skeletal muscle, x3) were used to fit prediction models with regard to ablation
      efficiency (nonperfused volume/treatment cell volume, y1) and ablation quality
      (grade 1-5, poor to excellent, y2), respectively, using the generalized
      estimating equation method. Cutoff values for achievement of treatment intent
      (efficiency >1.0; quality grade 4/5) were determined based on receiver operating
      characteristic curve analysis. Prediction performances were validated by
      calculating positive and negative predictive values. RESULTS: Generalized
      estimating equation analyses yielded models of y1 = 2.2637 - 0.0415x1 - 0.0011x2 
      0.0772x3 and y2 = 6.8148 - 0.1070x1 - 0.0050x2 - 0.2163x3. Cutoff values were
      1.312 for ablation efficiency (area under the curve, 0.7236; sensitivity, 0.6882;
      specificity, 0.6866) and 4.019 for ablation quality (0.8794; 0.7156; 0.9020).
      Positive and negative predictive values were 0.917 and 0.500 for ablation
      efficiency and 0.978 and 0.600 for ablation quality, respectively. CONCLUSIONS:
      Screening MRI-based prediction models for assessing immediate therapeutic
      responses of uterine fibroids to MR-HIFU ablation were fitted and validated,
      which may reduce the risk of unsuccessful treatment.

PMID- 26309185
TI  - Comprehensive Oncologic Imaging in Infants and Preschool Children With
      Substantially Reduced Radiation Exposure Using Combined Simultaneous 18F
      Fluorodeoxyglucose Positron Emission Tomography/Magnetic Resonance Imaging: A
      Direct Comparison to 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed
      Tomography.
AB  - OBJECTIVE: The aim of this study was to evaluate the clinical applicability and
      technical feasibility of fluorodeoxyglucose (FDG) positron emission tomography
      (PET)/magnetic resonance imaging (MRI) compared with FDG PET/computed tomography
      (CT) in young children focusing on lesion detection, PET quantification, and
      potential savings in radiation exposure. METHODS: Twenty examinations (10 PET/CT
      and 10 PET/MRI examinations) were performed prospectively in 9 patients with
      solid tumors (3 female, 6 male; mean age, 4.8 [1-6] years). Fluorodeoxyglucose
      PET/CT and FDG PET/MRI were performed sequentially after a single tracer
      injection. Lesion detection and analysis were performed independently in PET/CT
      and PET/MRI. Potential changes in diagnostic or therapeutic patient management
      were recorded. Positron emission tomography quantification in PET/MRI was
      evaluated by comparing standardized uptake values resulting from MRI-based and CT
      based attenuation correction. Effective radiation doses of PET and CT were
      estimated. RESULTS: Twenty-one PET-positive lesions were found congruently in
      PET/CT and PET/MRI. Magnetic resonance imaging enabled significantly better
      detection of morphologic PET correlates compared with CT. Eight suspicious PET
      negative lesions were identified by MRI, of which one was missed in CT.
      Sensitivity, specificity, and accuracy for correct lesion classification were not
      significantly different (90%, 47%, and 62% in PET/CT; 100%, 68%, and 79% in
      PET/MRI, respectively). In 4 patients, the use of PET/MRI resulted in a potential
      change in diagnostic management compared with PET/CT, as local and whole-body
      staging could be performed within 1 single examination. In 1 patient, PET/MRI
      initiated a change in therapeutic management. Positron emission tomography
      quantification using MRI-based attenuation correction was accurate compared with
      CT-based attenuation correction. Higher standardized uptake value deviations of
      about 18% were observed in the lungs due to misclassification in MRI-based
      attenuation maps. Potential reduction in radiation dose was 48% in PET/MRI
      compared with PET/CT (P < 0.05). CONCLUSIONS: FDG PET/MRI is at least equivalent
      to FDG PET/CT for oncologic imaging in young children. Specifically, superior
      soft tissue contrast of MRI results in higher confidence in lesion
      interpretation. Substantial savings in radiation exposure can be achieved, and
      the number of necessary imaging examinations can be reduced using PET/MRI
      compared with PET/CT.

PMID- 26309186
TI  - Contrast Gradient-Based Blood Velocimetry With Computed Tomography: Theory,
      Simulations, and Proof of Principle in a Dynamic Flow Phantom.
AB  - OBJECTIVES: The aim of this study was to introduce a new theoretical framework
      describing the relationship between the blood velocity, computed tomography (CT)
      acquisition velocity, and iodine contrast enhancement in CT images, and give a
      proof of principle of contrast gradient-based blood velocimetry with CT.
      MATERIALS AND METHODS: The time-averaged blood velocity (v(blood)) inside an
      artery along the axis of rotation (z axis) is described as the mathematical
      division of a temporal (Hounsfield unit/second) and spatial (Hounsfield
      unit/centimeter) iodine contrast gradient. From this new theoretical framework,
      multiple strategies for calculating the time-averaged blood velocity from
      existing clinical CT scan protocols are derived, and contrast gradient-based
      blood velocimetry was introduced as a new method that can calculate v(blood)
      directly from contrast agent gradients and the changes therein. Exemplarily, the
      behavior of this new method was simulated for image acquisition with an adaptive
      4-dimensional spiral mode consisting of repeated spiral acquisitions with
      alternating scan direction. In a dynamic flow phantom with flow velocities
      between 5.1 and 21.2 cm/s, the same acquisition mode was used to validate the
      simulations and give a proof of principle of contrast gradient-based blood
      velocimetry in a straight cylinder of 2.5 cm diameter, representing the aorta.
      RESULTS: In general, scanning with the direction of blood flow results in
      decreased and scanning against the flow in increased temporal contrast agent
      gradients. Velocity quantification becomes better for low blood and high
      acquisition speeds because the deviation of the measured contrast agent gradient
      from the temporal gradient will increase. In the dynamic flow phantom, a
      modulation of the enhancement curve, and thus alternation of the contrast agent
      gradients, can be observed for the adaptive 4-dimensional spiral mode and is in
      agreement with the simulations. The measured flow velocities in the downslopes of
      the enhancement curves were in good agreement with the expected values, although
      the accuracy and precision worsened with increasing flow velocities. CONCLUSIONS:
      The new theoretical framework increases the understanding of the relationship
      between the blood velocity, CT acquisition velocity, and iodine contrast
      enhancement in CT images, and it interconnects existing blood velocimetry methods
      with research on transluminary attenuation gradients. With these new insights,
      novel strategies for CT blood velocimetry, such as the contrast gradient-based
      method presented in this article, may be developed.

PMID- 26309187
TI  - Exposure to cigarette smoke downregulates beta2-adrenergic receptor expression
      and upregulates inflammation in alveolar macrophages.
AB  - Cigarette smoke-triggered inflammation is important in the pathophysiology of
      chronic obstructive pulmonary disease (COPD). beta2-Adrenergic receptor (beta2
      AR) is abundantly expressed on inflammatory cells, which is associated with
      inflammation regulation. To observe alterations in inflammation, pathological
      changes in lung tissues, and detect changes in beta2-AR expression, rats were
      exposed for 4 months to cigarette smoke. Pathological changes were observed in
      lung tissue sections. The levels of inflammatory mediators tumor necrosis factor
      (TNF)-alpha, interleukin (IL)-1beta in bronchoalveolar lavage fluid (BALF), and
      lung tissues were measured using enzyme-linked immunosorbent assay (ELISA).
      Nuclear factor (NF)-kappaB activity was detected by electrophoretic mobility
      shift assay (EMSA). Exposure to this regimen of cigarette smoke induced
      peribronchial and perivascular lymphocytic aggregates and parenchymal
      accumulation of macrophages in rats. EMSA demonstrated that smoke exposure
      enhanced NF-kappaB activation in rats' alveolar macrophages (AMs). Compared with
      the control group, smoke exposure induced a notable increase in TNF-alpha and IL
      1beta in BALF, lung tissues, and a decrease of beta2-AR expression of AMs. The
      expression of beta2-AR from AMs was inversely correlated with TNF-alpha and IL
      1beta levels of BALF. These data demonstrated that chronic smoke-triggered lung
      inflammation was accompanied by down-regulation of beta2-AR in rat lungs' AMs. 

PMID- 26309188
TI  - Invisible Mycosis Fungoides: Not to be Missed in Chronic Pruritus.
AB  - INTRODUCTION: Pruritus without visible dermatoses may be the first manifestation
      of hematological malignancies such as Hodgkin disease, chronic lymphocytic
      leukemia and mycosis fungoides (MF) and may precede the definitive diagnosis by
      weeks to years. CASE REPORT: We present a case of 'invisible' MF associated with
      chronic generalized pruritus in an elderly patient. CONCLUSION: Our case
      highlights the importance of performing skin biopsies in patients with chronic
      unexplained pruritus, especially in the absence of cutaneous lesions. This can
      prompt the clinician to consider possible underlying malignancy, such as
      'invisible' MF.

PMID- 26309189
TI  - Histopathologic and Cytogenetic Features of Pulmonary Adenoid Cystic Carcinoma.
AB  - INTRODUCTION: A significant portion of adenoid cystic carcinoma (ACC) cases are
      characterized by a t(6;9)(q22-23;p23-24) translocation that originates a MYB-NFIB
      fusion oncogene. The MYB-NFIB fusion oncoprotein activates transcription of MYB
      mediated pathways that impact cell cycle control, DNA repair, and apoptosis. This
      translocation seems highly specific for ACC. Moreover, therapies targeting MYB
      activated pathways to treat ACC are being explored. Pulmonary ACC (PACC) has not
      been thoroughly studied for rearrangements of the MYB gene. METHODS: Mayo Clinic
      Rochester surgical pathology archives (1972-2011) were searched for PACC. All
      cases were reviewed and classified according to the predominant histologic
      pattern (cribriform, solid, and tubular) by two surgical pathologists.
      Fluorescence in situ hybridization (FISH) was employed using a break-apart
      strategy to detect MYB rearrangement (at 6q23.3). Medical records were studied.
      RESULTS: Forty cases of PACC were studied; tissue blocks were available for FISH
      analysis in 35 cases. Six cases failed to hybridize. In 12 of 29 cases (41%), the
      MYB gene region was disrupted, whereas 17 cases (59%) showed no evidence of
      rearrangement. FISH studies performed on other histologic subtypes of lung cancer
      (10 squamous cell carcinomas, 10 adenocarcinomas, and 10 small-cell carcinomas)
      failed to show MYB rearrangement. There was no significant difference in MYB
      rearrangement status with respect to predominant histologic pattern, clinical
      features, or clinical outcome. CONCLUSIONS: A MYB rearrangement was identified in
      41% of PACC and was 100% specific. FISH studies for MYB may be of diagnostic
      utility in PACC, particularly on small biopsy specimens. MYB rearrangement in
      PACC does not seem to be associated with clinical features or prognosis.

PMID- 26309190
TI  - Spatiotemporal T790M Heterogeneity in Individual Patients with EGFR-Mutant Non
      Small-Cell Lung Cancer after Acquired Resistance to EGFR-TKI.
AB  - INTRODUCTION: Epidermal growth factor receptor (EGFR) mutation T790M accounts for
      approximately half of acquired resistances to EGFR-tyrosine kinase inhibitor
      (TKI). Because T790M is mediated by TKI exposure, its penetration and "on-off"
      may affect T790M status. METHODS: We retrospectively reviewed T790M status and
      clinical course of patients who had undergone multiple rebiopsies after acquired
      resistance to EGFR-TKI. RESULTS: Of 145 patients with EGFR-mutant NSCLC receiving
      rebiopsy after acquired resistance, 30 underwent multiple site rebiopsies, and 24
      received repeated rebiopsies at the same lesion. In 22 patients who underwent
      rebiopsies from both central nervous system (CNS; 20 cerebrospinal fluids [CSF]
      and 2 brain tumoral tissues) and thoracic lesions (7 lung tissues, 14 pleural
      effusions, and 1 lymph node), 12 were thoracic-T790M-positive. Of these 12
      patients, 10 were CNS-T790M-negative, despite exhibiting thoracic-T790M-positive.
      All 10 thoracic-T790M-negatives were CNS-T790M-negative. Three patients revealed
      a spatial heterogeneous T790M status among their thoracic lesions. In 24 patients
      receiving repeated rebiopsies at the same lesion (12 lung tissues, 6 CSFs, and 6
      pleural effusions), T790M status of lung lesions varied in five patients after
      TKI-free interval. In all five patients whose T790M status changed from positive
      to negative, EGFR-TKI rechallenge was effective. In three of these five patients,
      after further TKI exposure, T790M status changed from negative to positive again.
      There was also a patient whose CSF T790M status changed from negative to positive
      after high-dose erlotinib therapy. CONCLUSIONS: T790M status in an individual
      patient can be spatiotemporally heterogeneous because of selective pressure from
      EGFR-TKI.

PMID- 26309191
TI  - Safety and Immunogenicity of MAGE-A3 Cancer Immunotherapeutic with or without
      Adjuvant Chemotherapy in Patients with Resected Stage IB to III MAGE-A3-Positive
      Non-Small-Cell Lung Cancer.
AB  - INTRODUCTION: To assess the safety and immunogenicity of MAGE-A3
      immunotherapeutic in patients with stage IB-III MAGE-A3-positive non-small-cell
      lung cancer (NSCLC) who were or were not undergoing standard
      cisplatin/vinorelbine chemotherapy. METHODS: This open, prospective, multicenter,
      parallel-group phase I study (NCT00455572) enrolled patients with resected
      (cohorts 1-3) or unresectable (cohort 4) MAGE-A3-positive NSCLC. MAGE-A3
      immunotherapeutic (300 MUg recombinant MAGE-A3 formulated with AS15) was
      administered (eight doses, 3 weeks apart) concurrent with (cohort 1), after
      (cohort 2), or without (cohort 3) standard-adjuvant chemotherapy, or after
      standard radiotherapy and/or chemotherapy (cohort 4). RESULTS: Sixty-seven
      patients received greater than or equal to 1 dose of MAGE-A3 immunotherapeutic.
      Grade 3/4 adverse events (AEs) were reported for 16 out of 19 (84%), 2 out of 18
      (11%), 5 out of 18 (28%), and 1 out of 12 (8%) patients in cohorts 1, 2, 3, and
      4, respectively. Many grade 3/4 AEs in cohort 1 (e.g., neutropenia) were typical
      of chemotherapy. Six patients, including three in cohort 1, reported study
      treatment-related grade 3/4 AEs (injection-site reactions or musculoskeletal/back
      pain, which resolved within 5 days). One patient (in cohort 4) died, but this and
      the other serious adverse events were not study treatment related. MAGE-A3
      specific antibody responses to immunotherapy were induced in all patients
      evaluated in all cohorts. MAGE-A3-specific CD4 T-cell responses to immunotherapy
      were detected in 4 out of 11 (36%), 4 out of 15 (27%), 2 out of 8 (25%), and 5
      out of 6 (83%) evaluated patients in cohorts 1, 2, 3, and 4, respectively; and
      CD8 T-cell responses were only detected in four patients. CONCLUSION: In resected
      and unresectable NSCLC patients and irrespective of whether standard chemotherapy
      was concurrent or not, MAGE-A3 immunotherapeutic is well tolerated and induces
      MAGE-A3-specific immune responses.

PMID- 26309195
TI  - Sites of Chemistry in the Twentieth Century.

PMID- 26309192
TI  - Functional capacity, health status, and inflammatory biomarker profile in a
      cohort of patients with chronic obstructive pulmonary disease.
AB  - PURPOSE: Prior research has shown a significant relationship between 6-minute
      walking distance (6MWD) and health-related quality of life (HRQOL) in patients
      with chronic obstructive pulmonary disease (COPD). However, few studies have
      examined this relationship above and below the 350-m threshold that
      prognosticates survival and whether serum biomarkers could provide insight into
      the causes of quality-of-life differences above and below this threshold.
      METHODS: Measures of lung function, 6MWD, and HRQOL were compared in patients
      with COPD. Differences in HRQOL domains and serum biomarkers were compared in
      patients whose 6MWD were > or < 350 m. RESULTS: In patients walking < 350 m,
      scores in the physical domains of the SF-36 and the St. George's Respiratory
      Questionnaire (SGRQ) were significantly different from scores of their
      counterparts with greater 6MWD. However, there was no association between any
      biomarkers and the physical domains of the SF-36 and the SGRQ. In patients
      walking < 350 m, only the IL-8 levels were associated with lower scores in SF-36
      domains of emotional role, pain, vitality, and mental health (average r = -0.702;
      P = .01). In contrast, in patients walking > 350 m, surfactant protein D levels
      were associated with higher SF-36 scores in general pain, vitality, and social
      functioning (average r = 0.42; P = .04). CONCLUSIONS: In COPD, there is an
      association between 6MWD and the physical domains of the SF-36 and SGRQ in those
      patients walking < 350 m. The physical differences between patients walking < or
      > 350 m are not related to systemic inflammation. The association between
      interleukin 8 with nonphysical domains in patients with 6MWD < 350 m suggests
      that inflammation may play a larger role in the perceptive domain than previously
      recognized.

PMID- 26309196
TI  - From Science to Industry: The Sites of Aluminium in France from the Nineteenth to
      the Twentieth Century.
AB  - This paper explores the history of the isolation and industrial production of
      aluminium in France, from the work of Henri Sainte-Claire Deville in the 1850s to
      the latter part of the twentieth century, focusing on the relationships between
      academic research and industrial exploitation. In particular, it identifies a
      culture and organisation of research and development, "learning-by-doing," that
      emerged in the French aluminium industry following the establishment of the first
      electrolytic production facilities in the late 1880s by Paul Heroult, who, along
      with the American Charles Hall, patented the electrolytic method of producing the
      metal. This French method of R&D was a product both of a scientific culture that
      saw a continuity between scientific research and industrial application, and of a
      state policy that, unlike in Germany or the United States, was late to recognise
      the importance of fostering, on a large scale, the relations between academic
      chemistry and industry. It was only after World War II that the French state came
      fully to recognise the importance of underpinning industry with scientific
      research. And it was only from the 1960s, in the face of intensifying global
      competition, the risks of pollution, and the cost of energy, that the major
      aluminium firm Pechiney et Cie was able to replace a culture of "learning-by
      doing" by one that integrated fundamental science with the production process.

PMID- 26309194
TI  - Hypertriglyceridemic Waist Phenotype: Effect of Birthweight and Weight Gain in
      Childhood at 23 Years Old.
AB  - OBJECTIVE: To evaluate the association of birthweight and weight gain during
      different periods in childhood with the prevalence of hypertriglyceridemic waist
      phenotype (HWP). METHODS: In 1982, all hospitals births in Pelotas, South Brazil,
      were identified, and the 5914 liveborn were examined and their mothers
      interviewed. This population has been followed for several times. In 2004-05, we
      tried to follow the whole cohort and the subjects were interviewed, examined, and
      a blood sample was collected. HWP was defined as a triglycerides >= 2 mmol/L and
      a waist circumference >= 90 cm for men, and triglycerides >= 1.5 mmol/L and waist
      circumference >= 85 cm for woman. Poisson regression with robust adjustment of
      the variance was used to obtain adjusted estimates of the prevalence ratio.
      RESULTS: Subjects whose weight-for-age z-score at mean age of 42 months was one
      or more standard deviation above the mean, according to gender and age, were 8.77
      (95% confidence interval: 2.60; 29.64) times more likely of presenting the HWP
      than those subjects whose weight-for-age z-score at 42 months was more than one
      standard deviation below the mean. Among those subjects whose birthweight was
      adequate-for-gestational age (AGA), conditional weight at 20 months was
      positively associated to the risk of HWP [relative risk: 1.59 (95%: confidence
      interval: 1.32; 1.92)], whereas for small for gestational age (SGA) subjects
      conditional weight was not associated with HWP [relative risk: 1.05 (95%
      confidence interval: 0.77; 1.43)], p-value for interaction 0.08. CONCLUSION:
      Early weight gain among SGA infants, did not increase the risk of HWP in early
      adulthood, whereas among those who were AGA, early weight gain increased the risk
      of the having the phenotype in early adulthood.

PMID- 26309197
TI  - Propaganda and Philanthropy: The Institute Bento da Rocha Cabral, the Lisbon Site
      of Biochemistry (1925-1953).
AB  - This paper focuses on the internal organization and dynamics of the Institute
      Bento da Rocha Cabral (IRC) in Lisbon, a privately-funded institution devoted to
      biomedical research, from the particular vantage point of its laboratory of
      biochemistry; in particular, the process through which the institution turned
      from medically-related to chemically-related research in the period spanning from
      1925 to 1953. The history of the IRC raises interesting questions regarding the
      social politics of science as it materialized the desire of leading physicians of
      the Faculty of Medicine of Lisbon to create proper physical facilities for
      medically-related scientific research. We argue that the process which led to the
      creation of the IRC coincided with the gradual professional and political
      ascendance of physicians in Portuguese society initiated in the late nineteenth
      century, and is closely associated with Portuguese republicanism and the process
      of Lisbon becoming the scientific capital. 

PMID- 26309198
TI  - Flexibility or Inexactitude? The "Lab 60" at Karolinska Institutet: From Medical
      Disciplines towards the Modern Biomedical Complex.
AB  - In 1960, a new laboratory ("Lab 60") was built on the premises of Karolinska
      Institutet, Stockholm. This paper describes how the laboratory was envisioned.
      While planners and builders strove to optimise a generic laboratory, researchers
      argued for specialisation. The compromise was to enhance the reorganisation
      capability of the interior (flexibility) while simultaneously creating a
      "movable" institution consisting of researchers temporarily working in the
      laboratory for periods of three to five years, regardless of their disciplinary
      affiliation. Even though flexibility was not a novelty, the building succeeded as
      an organisational experiment and encouraged the abandonment of the model of one
      discipline, one professor, and one building in favour of a "movable" institution
      conducting temporary research. While the credibility of laboratories was
      established by their "placelessness" (anywhere), Lab 60 imitated multiple,
      heterogeneous sites (anything) in order to maintain credibility. As such, the lab
      embodied many sites between the disciplines of chemistry and medicine. 

PMID- 26309201
TI  - MAFsnp: A Multi-Sample Accurate and Flexible SNP Caller Using Next-Generation
      Sequencing Data.
AB  - Most existing statistical methods developed for calling single nucleotide
      polymorphisms (SNPs) using next-generation sequencing (NGS) data are based on
      Bayesian frameworks, and there does not exist any SNP caller that produces p
      values for calling SNPs in a frequentist framework. To fill in this gap, we
      develop a new method MAFsnp, a Multiple-sample based Accurate and Flexible
      algorithm for calling SNPs with NGS data. MAFsnp is based on an estimated
      likelihood ratio test (eLRT) statistic. In practical situation, the involved
      parameter is very close to the boundary of the parametric space, so the standard
      large sample property is not suitable to evaluate the finite-sample distribution
      of the eLRT statistic. Observing that the distribution of the test statistic is a
      mixture of zero and a continuous part, we propose to model the test statistic
      with a novel two-parameter mixture distribution. Once the parameters in the
      mixture distribution are estimated, p-values can be easily calculated for
      detecting SNPs, and the multiple-testing corrected p-values can be used to
      control false discovery rate (FDR) at any pre-specified level. With simulated
      data, MAFsnp is shown to have much better control of FDR than the existing SNP
      callers. Through the application to two real datasets, MAFsnp is also shown to
      outperform the existing SNP callers in terms of calling accuracy. An R package
      "MAFsnp" implementing the new SNP caller is freely available at
      http://homepage.fudan.edu.cn/zhangh/softwares/. 

PMID- 26309203
TI  - Gossypol acetate induced apoptosis of pituitary tumor cells by targeting the BCL
      2 via the upregulated microRNA miR-15a.
AB  - It is reported that gossypol acetate (GAA) has obvious effects on inhibiting the
      growth of tumors, by inhibiting the activity of enzymes. Ultrastructural study
      showed that GAA can cause morphological changes of mitochondria which leads to
      the apoptosis of tumors. However, little is known about the pathways that how the
      GAA triggers apoptosis of tumors and what kind of the molecular events have
      happened when GAA is added. The aim of the study is try to know if GAA have some
      functions on pituitary tumor cell. And if there are any changes after GAA
      treatment, we try to understand the mechanisms that how GAA regulate the growth
      of pituitary tumor cell. The study was carried out on rat lactotroph cell lines,
      GH3 and MMQ. Q-PCR and western blot (WB) assay are used to determine the
      expression level of genes and the protein level. Both the miR-15a (mimics)
      overexpression cell line and miR-15a knock out (inhibitor) cell line were
      obtained in GH3 and MMQ. Apoptosis rate was determined by flow cytometry (FCM).
      Our study revealed that: 1) GAA inhibits the proliferation of pituitary tumor
      cells of GH3, MMQ. 2) GAA upregulate the expression of miR15a in GH3 and MMQ. 3)
      Overexpressed miR-15a (mimics) downregulates the expression level of Bcl-2. 4)
      Knock down miR-15a (inhibitor) upregulates Bcl-2 and reverse the apoptosis
      induced by GAA. Our study indicates that GAA-induced decrease in cell
      proliferation is associated with decreased expression of Bcl-2 and increased miR
      15a. Based on this, we propose developing GAA as a novel therapeutic tool in the
      management of pituitary tumor. 

PMID- 26309202
TI  - Exosomes: emerging roles in communication between blood cells and vascular
      tissues during atherosclerosis.
AB  - PURPOSE OF REVIEW: Microvesicles, in general, and exosomes together with their
      delivered content in particular, are now being widely recognized as key players
      in atherosclerosis. We have previously reviewed the role of microvesicles in
      atherosclerosis pathogenesis, diagnosis and therapy. Here, we focus on the roles
      of exosomes and discuss their emergent role in mediating activation and response
      to inflammation, vessel infiltration and induction of coagulation. We will
      finally give an outlook to discuss novel detection techniques and systems biology
      based data analyses to investigate exosome-mediated cell-to-cell communication.
      RECENT FINDINGS: Recent research points to a role of exosomes in delivering
      apoptotic and inflammatory content between blood cells and vascular cells, with a
      potential contribution of exosomes secreted by adipose tissue. An
      atheroprotective role of exosomes in response to coagulation that may contrast
      with the procoagulatory role of platelet-derived larger microvesicles is
      envisaged. New detection and separation methods and systems biology techniques
      are emerging. CONCLUSION: We project that the development of novel detection,
      separation and analysis mechanism and systems-based analysis methods will further
      unravel the paracrine and endocrine 'communication protocol' between cellular
      players in atherosclerosis, mediating inflammation, oxidative stress and
      apoptosis.

PMID- 26309204
TI  - Globalizing Physician Assistant Education.

PMID- 26309205
TI  - Factors Predicting Physician Assistant Faculty Intent to Leave.
AB  - PURPOSE: To examine demographic, human capital, organizational, and environmental
      factors and their ability to predict physician assistant (PA) faculty intent to
      leave their current position. METHODS: The study was a nonexperimental, cross
      sectional predictive design. A random sample of 994 PA faculty drawn from the
      Physician Assistant Education Association (PAEA) database was invited to
      participate. Descriptive statistics were used to describe the respondents.
      Exploratory factor analysis was used to determine construct validity of the
      variables. Multiple regression analysis was used to examine the predictive
      ability of the independent variables on PA faculty intent to leave. RESULTS: The
      survey response rate was 34.5% (343/994). Data from 271 respondents were
      available for analysis (27.1%). Exploratory factor analysis identified 6 factors:
      the independent variables workload, autonomy, distributive justice, role
      conflict, and organizational support, and the dependent variable intent to leave.
      Mean Likert scale score for intent to leave was 3.06, indicating a low intent to
      leave. Regression analysis demonstrated a significant effect of the combination
      of independent variables on PA faculty intent to leave (F=9.86, P<.0001). The R
      was 0.40, indicating that approximately 40% of the variance in intent to leave
      was accounted for by the combination of independent variables in the model.
      Significant contributors were organizational support (beta=-0.41, P<.0001), role
      conflict (beta=0.15, P<.01), and age (beta=-0.13, P<.05). CONCLUSION: The results
      of this study demonstrate that organizational support, role conflict, and age are
      significant predictors of PA faculty intention to leave. These results have
      implications for faculty development and retention efforts.

PMID- 26309206
TI  - A Program Module to Supplement the Clinical Psychiatry Rotation for Physician
      Assistant Students.
AB  - A recent blog article aimed at prospective physician assistants (PAs) identified
      psychiatry as a series of Diagnostic and Statistical Manual of Mental Disorders,
      5th edition, diagnoses supplemented by empathy and medication. It suggested that
      there were ample opportunities for PAs to practice psychiatry, although a recent
      survey showed that only 1% of PA graduates were employed in psychiatric clinical
      practices. While this is only one perspective, it suggests that PAs'
      understanding of psychiatric practice is limited by the patient population they
      see during their clinical rotations as students. A broad systematically organized
      clinical psychiatry module with clinical preceptor direction could provide a more
      informed knowledge base and more interest in the field. 

PMID- 26309207
TI  - A Penny for Your Thoughts: Intellectual Property and the Ownership of Video
      Captured Lectures.

PMID- 26309208
TI  - Understanding Validity in Evidence-Based Medicine.

PMID- 26309209
TI  - Rainforest Physician Assistants--The Papua New Guinea Health Extension Officer:
      An International Physician Assistant Analogue.

PMID- 26309210
TI  - Medical Directors' Roles in the Strategic Planning for Physician Assistant
      Education.

PMID- 26309211
TI  - Considering Point-of-Care Electronic Medical Resources in Lieu of Traditional
      Textbooks for Medical Education.
AB  - Selecting resources to support didactic courses is a critical decision, and the
      advantages and disadvantages must be carefully considered. During clinical
      rotations, students not only need to possess strong background knowledge but also
      are expected to be proficient with the same evidence-based POC resources used by
      clinicians. Students place high value on "real world" learning and therefore may
      place more value on POC resources that they know practicing clinicians use as
      compared with medical textbooks. The condensed nature of PA education requires
      students to develop background knowledge and information literacy skills over a
      short period. One way to build that knowledge and those skills simultaneously is
      to use POC resources in lieu of traditional medical textbooks during didactic
      training. Electronic POC resources offer several advantages over traditional
      textbooks and should be considered as viable options in PA education.

PMID- 26309212
TI  - A series of new manganese thioarsenates(v) based on different unsaturated
      [Mn(amine)x](2+) complexes.
AB  - A series of new manganese thioarsenates(V) [Mn(en)2Cu(AsVS4)]n (1, en =
      ethylenediamine), [Mn(dien)2][Mn(dien)(AsVS4)]2 (2, dien = diethylenetriamine),
      [Mn(teta)(AsVS4)]n (3, teta = triethylenetetramine), and
      {[Mn(dap)2][Mn(dap)(AsVS4)]2}n (4, dap = 1,2-diaminopropane) have been
      solvothermally synthesized and structurally characterized. 1 displays a neutral
      heterometallic [Mn(en)2Cu(AsVS4)]n chain built up from the linkages of
      [Mn(en)2]2+ complexes and infinite heterometallic [Cu(AsVS4)2-]n chains, and
      represents the only example of incorporation of an unsaturated [Mn(en)2]2+
      complex into the 1-D [Cu(AsVS4)2-]n framework. 2 consists of a discrete
      {[Mn(dien)]2(AsVS4)2}2- cluster and a charge compensating complex cation
      [Mn(dien)2]2+. 3 shows a 1-D neutral [Mn(teta)(AsVS4)]n chain constructed by the
      combination of both complex [Mn(teta)]2+ ions and tetrahedral [AsVS4]3- anions. 4
      exhibits a rare 2-D {[Mn(dap)2][Mn(dap)(AsVS4)]2}n layer based on the linkages of
      [AsVS4]3- anions and [Mn(dap)x]2+ (x = 1, 2) groups. These results show that
      different unsaturated [Mn(amine)x]2+ complexes are directly bonded to [AsVS4]3-
      anions to give different manganese thioarsenates(V), which have a significant
      structure directing effect on the structures of manganese thioarsenates(V) under
      similar solvothermal conditions. The present compounds exhibit wide-band-gap
      semiconducting properties with absorption band edges between 2.00 and 2.58 eV,
      and density functional theory calculations for compounds 1, 3 and 4 have also
      been performed.

PMID- 26309213
TI  - Saving Supersick Patients Undergoing Liver Transplant.

PMID- 26309214
TI  - Associations between Meteorological Parameters and Influenza Activity in Berlin
      (Germany), Ljubljana (Slovenia), Castile and Leon (Spain) and Israeli Districts.
AB  - BACKGROUND: Studies in the literature have indicated that the timing of seasonal
      influenza epidemic varies across latitude, suggesting the involvement of
      meteorological and environmental conditions in the transmission of influenza. In
      this study, we investigated the link between meteorological parameters and
      influenza activity in 9 sub-national areas with temperate and subtropical
      climates: Berlin (Germany), Ljubljana (Slovenia), Castile and Leon (Spain) and
      all 6 districts in Israel. METHODS: We estimated weekly influenza-associated
      influenza-like-illness (ILI) or Acute Respiratory Infection (ARI) incidence to
      represent influenza activity using data from each country's sentinel surveillance
      during 2000-2011 (Spain) and 2006-2011 (all others). Meteorological data was
      obtained from ground stations, satellite and assimilated data. Two generalized
      additive models (GAM) were developed, with one using specific humidity as a
      covariate and another using minimum temperature. Precipitation and solar
      radiation were included as additional covariates in both models. The models were
      adjusted for previous weeks' influenza activity, and were trained separately for
      each study location. RESULTS: Influenza activity was inversely associated
      (p<0.05) with specific humidity in all locations. Minimum temperature was
      inversely associated with influenza in all 3 temperate locations, but not in all
      subtropical locations. Inverse associations between influenza and solar radiation
      were found in most locations. Associations with precipitation were location
      dependent and inconclusive. We used the models to estimate influenza activity a
      week ahead for the 2010/2011 period which was not used in training the models.
      With exception of Ljubljana and Israel's Haifa District, the models could closely
      follow the observed data especially during the start and the end of epidemic
      period. In these locations, correlation coefficients between the observed and
      estimated ranged between 0.55 to 0.91and the model-estimated influenza peaks were
      within 3 weeks from the observations. CONCLUSION: Our study demonstrated the
      significant link between specific humidity and influenza activity across
      temperate and subtropical climates, and that inclusion of meteorological
      parameters in the surveillance system may further our understanding of influenza
      transmission patterns.

PMID- 26309215
TI  - Exploring Cultural Differences in the Recognition of the Self-Conscious Emotions.
AB  - Recent research suggests that the self-conscious emotions of embarrassment,
      shame, and pride have distinct, nonverbal expressions that can be recognized in
      the United States at above-chance levels. However, few studies have examined the
      recognition of these emotions in other cultures, and little research has been
      conducted in Asia. Consequently the cross-cultural generalizability of self
      conscious emotions has not been firmly established. Additionally, there is no
      research that examines cultural variability in the recognition of the self
      conscious emotions. Cultural values and exposure to Western culture have been
      identified as contributors to variability in recognition rates for the basic
      emotions; we sought to examine this for the self-conscious emotions using the
      University of California, Davis Set of Emotion Expressions (UCDSEE). The present
      research examined recognition of the self-conscious emotion expressions in South
      Korean college students and found that recognition rates were very high for
      pride, low but above chance for shame, and near zero for embarrassment. To
      examine what might be underlying the recognition rates we found in South Korea,
      recognition of self-conscious emotions and several cultural values were examined
      in a U.S. college student sample of European Americans, Asian Americans, and
      Asian-born individuals. Emotion recognition rates were generally similar between
      the European Americans and Asian Americans, and higher than emotion recognition
      rates for Asian-born individuals. These differences were not explained by
      cultural values in an interpretable manner, suggesting that exposure to Western
      culture is a more important mediator than values. 

PMID- 26309216
TI  - Speaking and Listening with the Eyes: Gaze Signaling during Dyadic Interactions.
AB  - Cognitive scientists have long been interested in the role that eye gaze plays in
      social interactions. Previous research suggests that gaze acts as a signaling
      mechanism and can be used to control turn-taking behaviour. However, early
      research on this topic employed methods of analysis that aggregated gaze
      information across an entire trial (or trials), which masks any temporal dynamics
      that may exist in social interactions. More recently, attempts have been made to
      understand the temporal characteristics of social gaze but little research has
      been conducted in a natural setting with two interacting participants. The
      present study combines a temporally sensitive analysis technique with modern eye
      tracking technology to 1) validate the overall results from earlier aggregated
      analyses and 2) provide insight into the specific moment-to-moment temporal
      characteristics of turn-taking behaviour in a natural setting. Dyads played two
      social guessing games (20 Questions and Heads Up) while their eyes were tracked.
      Our general results are in line with past aggregated data, and using cross
      correlational analysis on the specific gaze and speech signals of both
      participants we found that 1) speakers end their turn with direct gaze at the
      listener and 2) the listener in turn begins to speak with averted gaze.
      Convergent with theoretical models of social interaction, our data suggest that
      eye gaze can be used to signal both the end and the beginning of a speaking turn
      during a social interaction. The present study offers insight into the temporal
      dynamics of live dyadic interactions and also provides a new method of analysis
      for eye gaze data when temporal relationships are of interest. 

PMID- 26309218
TI  - 3D nanochannel electroporation for high-throughput cell transfection with high
      uniformity and dosage control.
AB  - Of great interest to modern medicine and biomedical research is the ability to
      inject individual target cells with the desired genes or drug molecules. Some
      advances in cell electroporation allow for high throughput, high cell viability,
      or excellent dosage control, yet no platform is available for the combination of
      all three. In an effort to solve this problem, here we show a "3D nano-channel
      electroporation (NEP) chip" on a silicon platform designed to meet these three
      criteria. This NEP chip can simultaneously deliver the desired molecules into
      40,000 cells per cm(2) on the top surface of the device. Each 650 nm pore aligns
      to a cell and can be used to deliver extremely small biological elements to very
      large plasmids (>10 kbp). When compared to conventional bulk electroporation
      (BEP), the NEP chip shows a 20 fold improvement in dosage control and uniformity,
      while still maintaining high cell viability (>90%) even in cells such as cardiac
      cells which are characteristically difficult to transfect. This high-throughput
      3D NEP system provides an innovative and medically valuable platform with uniform
      and reliable cellular transfection, allowing for a steady supply of healthy,
      engineered cells.

PMID- 26309217
TI  - Angiopoietin/Tie2 Dysbalance Is Associated with Acute Kidney Injury after Cardiac
      Surgery Assisted by Cardiopulmonary Bypass.
AB  - INTRODUCTION: The pathophysiology of acute kidney injury (AKI) after cardiac
      surgery is not completely understood. Recent evidence suggests a pivotal role for
      the endothelium in AKI. In experimental models of AKI, the endothelial specific
      receptor Tie2 with its ligands Angiopoietin (Ang) 1 and Ang2 are deranged. This
      study investigates their status after cardiac surgery, and a possible relation
      between angiopoietins and AKI. METHODS: From a cohort of 541 patients that
      underwent cardiac surgery, blood and urine was collected at 5 predefined time
      points. From this cohort we identified 21 patients who had at least 50% post
      operative serum creatinine increase (AKI). We constructed a control group (n =
      21) using propensity matching. Systemic levels of Ang1, Ang2, and sTie2 were
      measured in plasma and the AKI markers albumin, kidney injury molecule-1 (KIM-1)
      and N-acetyl-beta-D-glucosaminidase (NAG) were measured in the urine. RESULTS:
      Ang2 plasma levels increased over time in AKI (from 4.2 to 11.6 ng/ml) and
      control patients (from 3.0 to 6.7 ng/ml). Ang2 levels increased 1.7-fold more in
      patients who developed AKI after cardiac surgery compared to matched control
      patients. Plasma levels of sTie2 decreased 1.6-fold and Ang1 decreased 3-fold
      over time in both groups, but were not different between AKI and controls (Ang1 P
      = 0.583 and sTie2 P = 0.679). Moreover, we found a positive correlation between
      plasma levels of Ang2 and urinary levels of NAG. CONCLUSIONS: The endothelial
      Ang/Tie2 system is in dysbalance in patients that develop AKI after cardiac
      surgery compared to matched control patients.

PMID- 26309219
TI  - An Analysis of Factors Affecting Genotyping Success from Museum Specimens Reveals
      an Increase of Genetic and Morphological Variation during a Historical Range
      Expansion of a European Spider.
AB  - Natural history collections house an enormous amount of plant and animal
      specimens, which constitute a promising source for molecular analyses. Storage
      conditions differ among taxa and can have a dramatic effect on the success of DNA
      work. Here, we analyze the feasibility of DNA extraction from ethanol preserved
      spiders (Araneae). We tested genotyping success using several hundred specimens
      of the wasp spider, Argiope bruennichi, deposited in two large German natural
      history collections. We tested the influence of different factors on the utility
      of specimens for genotyping. Our results show that not the specimen's age, but
      the museum collection is a major predictor of genotyping success. These results
      indicate that long term storage conditions should be optimized in natural history
      museums to assure the utility of collections for DNA work. Using historical
      material, we also traced historical genetic and morphological variation in the
      course of a poleward range expansion of A. bruennichi by comparing contemporary
      and historical specimens from a native and an invasive population in Germany. We
      show that the invasion of A. bruennichi is tightly correlated with an historical
      increase of genetic and phenotypic variation in the invasive population. 

PMID- 26309220
TI  - Benzyl anion transfer in the fragmentation of N-(phenylsulfonyl)
      benzeneacetamides: a gas-phase intramolecular S(N)Ar reaction.
AB  - In this study, we report a gas-phase benzyl anion transfer via intramolecular
      aromatic nucleophilic substitution (SNAr) during the course of tandem mass
      spectrometry of deprotonated N-(phenylsulfonyl)-benzeneacetamide. Upon
      collisional activation, the formation of the initial ion/neutral complex
      ([C6H5CH2(-)/C6H5SO2NCO]), which was generated by heterolytic cleavage of the CH2
      CO bond, is proposed as the key step. Subsequently, the anionic counterpart,
      benzyl anion, is transferred to conduct the intra-complex SNAr reaction. After
      losing neutral HNCO, the intermediate gives rise to product ion B at m/z 231,
      whose structure is confirmed by comparing the multistage spectra with those of
      deprotonated 2-benzylbenzenesulfinic acid and (benzylsulfonyl)benzene. In
      addition, intra-complex proton transfer is also observed within the complex
      [C6H5CH2(-)/C6H5SO2NCO] to generate product ion C at m/z 182. The INC-mediated
      mechanism was corroborated by theoretical calculations, isotope experiments,
      breakdown curve, substituent experiments, etc. This work may provide further
      understanding of the physicochemical properties of the gaseous benzyl anion. 

PMID- 26309221
TI  - UTE imaging with simultaneous water and fat signal suppression using a time
      efficient multispoke inversion recovery pulse sequence.
AB  - PURPOSE: The long repetition time and inversion time with inversion recovery
      preparation ultrashort echo time (UTE) often causes prohibitively long scan
      times. We present an optimized method for long T2 signal suppression in which
      several k-space spokes are acquired after each inversion preparation. THEORY AND
      METHODS: Using Bloch equations the sequence parameters such as TI and flip angle
      were optimized to suppress the long T2 water and fat signals and to maximize
      short T2 contrast. Volunteer imaging was performed on a healthy male volunteer.
      Inversion recovery preparation was performed using a Silver-Hoult adiabatic
      inversion pulse together with a three-dimensional (3D) UTE (3D Cones)
      acquisition. RESULTS: The theoretical signal curves generally agreed with the
      experimentally measured region of interest curves. The multispoke inversion
      recovery method showed good muscle and fatty bone marrow suppression, and
      highlighted short T2 signals such as these from the femoral and tibial cortex.
      CONCLUSION: Inversion recovery 3D UTE imaging with multiple spoke acquisitions
      can be used to effectively suppress long T2 signals and highlight short T2
      signals within clinical scan times. Theoretical modeling can be used to determine
      sequence parameters to optimize long T2 signal suppression and maximize short T2
      signals. Experimental results on a volunteer confirmed the theoretical
      predictions. Magn Reson Med 76:577-582, 2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 26309222
TI  - A High-Throughput Kinetic Assay for RNA-Cleaving Deoxyribozymes.
AB  - Determining kinetic constants is important in the field of RNA-cleaving
      deoxyribozymes (DNAzymes). Using todays conventional gel assays for DNAzyme
      assays is time-consuming and laborious. There have been previous attempts at
      producing new and improved assays; however these have drawbacks such as
      incompatibility with structured DNAzymes, enzyme or substrate modifications and
      increased cost. Here we present a new method for determining single-turnover
      kinetics of RNA-cleaving DNAzymes in real-time and in a high-throughput fashion.
      The assay is based on an intercalating fluorescent dye, PicoGreen, with high
      specificity for double-stranded DNA and heteroduplex DNA-RNA in this case formed
      between the DNAzyme and the target RNA. The fluorescence decreases as substrate
      is converted to product and is released from the enzyme. Using a Flexstation II
      multimode plate reader with built in liquid handling we could automate parts of
      the assay. This assay gives the possibility to determine single-turnover kinetics
      for up to 48 DNAzymes simultaneously. As the fluorescent probe is extrinsic there
      is no need for enzyme or substrate modifications, making this method less costly
      compared to other methods. The main novelty of this assay is the possibility of
      using full-length mRNA as the DNAzyme target. 

PMID- 26309223
TI  - Comparative study of the validity of three regions of the 18S-rRNA gene for
      massively parallel sequencing-based monitoring of the planktonic eukaryote
      community.
AB  - The nuclear 18S-rRNA gene has been used as a metabarcoding marker in massively
      parallel sequencing (MPS)-based environmental surveys for plankton biodiversity
      research. However, different hypervariable regions have been used in different
      studies, and their utility has been debated among researchers. In this study,
      detailed investigations into 18S-rRNA were carried out; we investigated the
      effective number of sequences deposited in international nucleotide sequence
      databases (INSDs), the amplification bias, and the amplicon sequence variability
      among the three variable regions, V1-3, V4-5 and V7-9, using in silico polymerase
      chain reaction (PCR) amplification based on INSDs. We also examined the primer
      universality and the taxonomic identification power, using MPS-based
      environmental surveys in the Sea of Okhotsk, to determine which region is more
      useful for MPS-based monitoring. The primer universality was not significantly
      different among the three regions, but the number of sequences deposited in INSDs
      was markedly larger for the V4-5 region than for the other two regions. The
      sequence variability was significantly different, with the highest variability in
      the V1-3 region, followed by the V7-9 region, and the lowest variability in the
      V4-5 region. The results of the MPS-based environmental surveys showed
      significantly higher identification power in the V1-3 and V7-9 regions than in
      the V4-5 region, but no significant difference was detected between the V1-3 and
      V7-9 regions. We therefore conclude that the V1-3 region will be the most
      suitable for future MPS-based monitoring of natural eukaryote communities, as the
      number of sequences deposited in INSDs increases.

PMID- 26309224
TI  - Dehydroepiandrosterone Attenuates Cocaine-Seeking Behaviour Independently of
      Corticosterone Fluctuations.
AB  - The neurosteroid dehydroepiandrosterone (DHEA) is involved in the pathophysiology
      of several psychiatric disorders, including cocaine addiction. We have previously
      shown that DHEA attenuates cocaine-seeking behaviour, and also that DHEA
      decreases corticosterone (CORT) levels in plasma and the prefrontal cortex.
      Previous studies have found that rats demonstrate cocaine-seeking behaviour only
      when the level of CORT reaches a minimum threshold. In the present study, we
      investigated whether the attenuating effect of DHEA on cocaine seeking is a
      result of it reducing CORT levels rather than a result of any unique neurosteroid
      properties. Rats received either daily DHEA injections (2 mg/kg, i.p.) alone,
      daily DHEA (2 mg/kg, i.p.) with CORT infusion (to maintain stable basal levels of
      CORT; 15 mg/kg, s.c.) or vehicle (i.p.) as control, throughout self
      administration training and extinction sessions. We found that both DHEA-treated
      and DHEA + CORT-treated groups showed a significantly lower number of active
      lever presses compared to controls throughout training and extinction sessions,
      as well as at cocaine-primed reinstatement. DHEA-treated rats showed lower CORT
      levels throughout the experimental phases compared to DHEA + CORT-treated and
      control rats. Additionally, we show that DHEA administered to cocaine-trained
      rats throughout extinction sessions, or immediately before reinstatement,
      attenuated cocaine seeking. These findings indicate that DHEA attenuates cocaine
      seeking behaviour independently of fluctuations in CORT levels. 

PMID- 26309225
TI  - The c.503T>C Polymorphism in the Human KLRB1 Gene Alters Ligand Binding and
      Inhibitory Potential of CD161 Molecules.
AB  - Studying genetic diversity of immunologically relevant molecules can improve our
      knowledge on their functional spectrum in normal immune responses and may also
      uncover a possible role of different variants in diseases. We characterized the
      c.503T>C polymorphism in the human KLRB1 gene (Killer cell lectin-like receptor,
      subfamily B, member 1) coding for the cell surface receptor CD161. CD161 is
      expressed by subsets of CD4+ and CD8+ T cells and the great majority of CD56+
      natural killer (NK) cells, acting as inhibitory receptor in the latter
      population. Genotyping a cohort of 118 healthy individuals revealed 40% TT
      homozygotes, 46% TC heterozygotes, and 14% carriers of CC. There was no
      difference in the frequency of CD161 expressing CD4+ and CD8+ T cells between the
      different genotypes. However, the frequency of CD161+ NK cells was significantly
      decreased in CC carriers as compared to TT homozygotes. c.503T>C causes an amino
      acid exchange (p.Ile168Thr) in an extracellular loop of the CD161 receptor, which
      is regarded to be involved in binding of its ligand Lectin-like transcript 1
      (LLT1). Binding studies using soluble LLT1-Fc on 293 transfectants over
      expressing CD161 receptors from TT or CC carriers suggested diminished binding to
      the CC variant. Furthermore, triggering of CD161 either by LLT1 or anti-CD161
      antibodies inhibited NK cell activation less effectively in cells from CC
      individuals than cells from TT carriers. These data suggest that the c.503T>C
      polymorphism is associated with structural alterations of the CD161 receptor. The
      regulation of NK cell homeostasis and activation apparently differs between
      carriers of the CC and TT variant of CD161. 

PMID- 26309227
TI  - Methylprednisolone use during radiotherapy extenuates hearing loss in patients
      with nasopharyngeal carcinoma.
AB  - OBJECTIVES/HYPOTHESIS: To investigate the hearing protective effects of
      methylprednisolone use during radiotherapy in patients with nasopharyngeal
      carcinoma. STUDY DESIGN: Prospective, controlled clinical study. METHODS: Fifty
      three patients with nasopharyngeal carcinoma (106 ears). Twenty-five patients (50
      ears) received radiotherapy with intravenous methylprednisolone for 14 days, and
      another 28 patients (56 ears) received radiotherapy alone. Pure tone audiometry,
      distortion product otoacoustic emission (DPOAE), and auditory brainstem responses
      (ABR) results were reviewed before and 1 year after radiotherapy. RESULT: One
      year after radiotherapy, the air-and-bone conduction pure tone hearing thresholds
      increased, and the DPOAE levels decreased in the control group. There was no
      difference in the ABR wave I, III, and V latencies and the I to V interwave
      latencies before and 1 year after radiotherapy. The pure tone air conduction
      thresholds decreased, and the DPOAE levels increased in the treatment group
      compared with the control group. CONCLUSION: Early sensorineural hearing loss
      after radiotherapy primarily affected the outer hair cells. The use of
      methylprednisolone during radiotherapy can extenuate early sensorineural hearing
      loss caused by irradiation.

PMID- 26309226
TI  - Albuminuria Is Associated with Traditional Cardiovascular Risk Factors and Viral
      Load in HIV-Infected Patients in Rural South Africa.
AB  - CONTEXT: As life expectancy improves among Human Immunodeficiency Virus (HIV)
      patients, renal and cardiovascular diseases are increasingly prevalent in this
      population. Renal and cardiovascular disease are mutual risk factors and are
      characterized by albuminuria. Understanding the interactions between HIV,
      cardiovascular risk factors and renal disease is the first step in tackling this
      new therapeutic frontier in HIV. METHODS: In a rural primary health care centre,
      903 HIV-infected adult patients were randomly selected and data on HIV-infection
      and cardiovascular risk factors were collected. Glomerular filtration rate (eGFR)
      was estimated. Albuminuria was defined as an Albumin-Creatinine-Ratio above 30
      mg/g. Multivariate logistic regression analysis was used to analyse albuminuria
      and demographic, clinical and HIV-associated variables. RESULTS: The study
      population consisted of 903 HIV-infected patients, with a median age of 40 years
      (Inter-Quartile Range (IQR) 34-48 years), and included 625 (69%) women. The
      median duration since HIV diagnosis was 26 months (IQR 12-58 months) and 787
      (87%) received antiretroviral therapy. Thirty-six (4%) of the subjects were shown
      to have diabetes and 205 (23%) hypertension. In the cohort, 21% had albuminuria
      and 2% an eGFR <60 mL/min/1.73m2. Albuminuria was associated with hypertension
      (adjusted odds ratio (aOR) 1.59; 95% confidence interval (CI) 1.05-2.41; p<0.05),
      total cholesterol (aOR 1.31; 95% CI 1.11-1.54; p<0.05), eGFR (aOR 0.98; 95% CI
      0.97-0.99; p<0.001) and detectable viral load (aOR 2.74; 95% CI 1.56-4.79;
      p<0.001). Hypertension was undertreated: 78% were not receiving treatment, while
      another 11% were inadequately treated. No patients were receiving lipid-lowering
      medication. CONCLUSION: Glomerular filtration rate was well conserved, while
      albuminuria was common amongst HIV-infected patients in rural South Africa. Both
      cardiovascular and HIV-specific variables were associated with albuminuria.
      Improved cardiovascular risk prevention as well as adequate virus suppression
      might be the key to escape the vicious circle of renal failure and cardiovascular
      disease and improve the long-term prognosis of HIV-infected patients.

PMID- 26309228
TI  - Direct Age Determination of a Subtropical Freshwater Crayfish (Redclaw, Cherax
      quadricarinatus) Using Ossicular Growth Marks.
AB  - Recent studies have reported that crustacean age determination is possible. We
      applied a direct ageing method (i.e. transverse cross sectioning of gastric
      ossicles) to a subtropical freshwater crayfish (Cherax quadricarinatus) sourced
      from an aquaculture population. Growth mark periodicity and the potential for
      chronological depositions were investigated by staining C. quadricarinatus with
      calcein and examining their ossicles a year later. Pterocardiac ossicles were
      superior to other ageing structures (i.e. other ossicles and eyestalks) and
      produced repeatable between-reader counts (87% were corroborated and 13% varied
      by +/-1). C. quadricarinatus size-at-age data (for an aquaculture population) was
      described by a von Bertalanffy growth equation (Linfinity = 32 mm occipital
      carapace length; K = 0.64; t0 = -0.18; R2 = 0.81). Ossicular growth marks did not
      correspond to moult history. The calcein stain was retained over an annual cycle
      comprising multiple moults, demonstrating that pterocardiac ossicles retain
      chronological information. The maximum age (3+) corroborated other indirectly
      obtained longevity estimates for C. quadricarinatus. Multiple lines of evidence
      indicate that the growth marks in C. quadricarinatus ossicles are probably
      deposited annually during winter. The ability to extract age information from
      subtropical decapods provides substantial opportunities for advancing fisheries
      and conservation research globally, but further research is needed to provide a
      definitive validation and elucidate the mechanism governing the accrual of
      ossicular growth marks. 

PMID- 26309229
TI  - Soft tissue fillers as non-specific modulators of adipogenesis: change of the
      paradigm?
AB  - Dermal filler injection is a cornerstone of facial rejuvenation procedures. Based
      on available data in animal and human studies, we suppose that the activation and
      proliferation of adipose-derived stem cells and expansion of mature adipocytes
      play a crucial role in long-term effects of volumizing, tissue tightening and
      beautification. 

PMID- 26309230
TI  - Oral Malignant Acanthosis Nigricans and Tripe Palms Associated With Renal
      Urothelial Carcinoma.

PMID- 26309231
TI  - A Crimean-Congo hemorrhagic fever (CCHF) viral vaccine expressing nucleoprotein
      is immunogenic but fails to confer protection against lethal disease.
AB  - Crimean-Congo Hemorrhagic Fever (CCHF) is a severe tick-borne disease, endemic in
      many countries in Africa, the Middle East, Eastern Europe and Asia. Between 15
      70% of reported cases are fatal with no approved vaccine available. In the
      present study, the attenuated poxvirus vector, Modified Vaccinia virus Ankara,
      was used to develop a recombinant candidate vaccine expressing the CCHF virus
      nucleoprotein. Cellular and humoral immunogenicity was confirmed in 2 mouse
      strains, including type I interferon receptor knockout mice, which are
      susceptible to CCHF disease. Despite the immune responses generated post
      immunisation, the vaccine failed to protect animals from lethal disease in a
      challenge model. 

PMID- 26309232
TI  - Attentional Biases toward Attractive Alternatives and Rivals: Mechanisms Involved
      in Relationship Maintenance among Chinese Women.
AB  - A long-term romantic relationship can offer many benefits to committed
      individuals. Thus, humans possess relationship maintenance mechanisms to protect
      against threats from those who serve as attractive alternatives or intrasexual
      rivals. Many studies have indicated that romantic love can act as a commitment
      device to activate these mechanisms. To examine the attentional bias associated
      with relationship maintenance among 108 college students (49 single and 59
      committed females) in China, we used a semantic priming procedure to activate
      mental representations associated with romantic love and then asked participants
      to complete a dot-probe task for the purpose of making a distinction between the
      engage and disengage components of attention. No significant engaging effects
      toward attractive faces were observed among committed females, but the following
      significant disengaging effects were found: when primed with romantic love,
      single females showed increased attention toward and difficulty in disengaging
      from attractive male faces, whereas females already in a committed relationship
      did not alter their attention, remaining as inattentive to attractive
      alternatives as they were in the baseline condition. In addition, committed
      females responded to love priming by exhibiting difficulty in disengaging from
      attractive rivals. The present findings provide evidence in the Chinese cultural
      context for the existence of early-stage attentional processes in the domain of
      relationship maintenance that committed Chinese females protected an ongoing
      relationship by not only being inattentive to attractive males who could serve as
      attractive alternatives, but also being more attentive to attractive females who
      could be potential rivals when mental representations associated with romantic
      love were primed. 

PMID- 26309233
TI  - Anti-TNF alpha medications and neuropathy.
AB  - We studied the clinical, electrophysiological, and pathological features,
      outcome, and frequency of anti-tumor necrosis factor alpha (a-TNF) medications
      induced neuropathies (ATIN) in patients with inflammatory disorders. Of 2,017
      patients treated with a-TNF medication, 12 patients met our inclusion criteria
      for a prevalence of 0.60% and an incidence of 0.4 cases per 1,000 person-years.
      The median time from a-TNF medication treatment to ATIN was 16.8 months (range 2
      60 months). Six patients had focal or multifocal peripheral neuropathies. The
      other six had generalized neuropathies. For all, a-TNF medication was stopped.
      Seven patients received immunoglobulin infusions. ATIN outcome was favorable in
      all but one patient. ATINs are rare and heterogeneous neuropathies. In 10
      patients, the neuropathy was "inflammatory", suggesting that it could be due to
      systemic pro-inflammatory effects of a-TNF agents. 

PMID- 26309234
TI  - Response to Wnt Signaling Pathways.

PMID- 26309235
TI  - Monte Carlo study of microdosimetric diamond detectors.
AB  - Ion-beam therapy provides a high dose conformity and increased radiobiological
      effectiveness with respect to conventional radiation-therapy. Strict constraints
      on the maximum uncertainty on the biological weighted dose and consequently on
      the biological weighting factor require the determination of the radiation
      quality, defined as the types and energy spectra of the radiation at a specific
      point. However the experimental determination of radiation quality, in particular
      for an internal target, is not simple and the features of ion interactions and
      treatment delivery require dedicated and optimized detectors. Recently chemical
      vapor deposition (CVD) diamond detectors have been suggested as ion-beam therapy
      microdosimeters. Diamond detectors can be manufactured with small cross sections
      and thin shapes, ideal to cope with the high fluence rate. However the sensitive
      volume of solid state detectors significantly deviates from conventional
      microdosimeters, with a diameter that can be up to 1000 times the height. This
      difference requires a redefinition of the concept of sensitive thickness and a
      deep study of the secondary to primary radiation, of the wall effects and of the
      impact of the orientation of the detector with respect to the radiation field.
      The present work intends to study through Monte Carlo simulations the impact of
      the detector geometry on the determination of radiation quality quantities, in
      particular on the relative contribution of primary and secondary radiation. The
      dependence of microdosimetric quantities such as the unrestricted linear energy L
      and the lineal energy y are investigated for different detector cross sections,
      by varying the particle type (carbon ions and protons) and its energy. 

PMID- 26309236
TI  - Structure of T4moF, the Toluene 4-Monooxygenase Ferredoxin Oxidoreductase.
AB  - The 1.6 A crystal structure of toluene 4-monooxygenase reductase T4moF is
      reported. The structure includes ferredoxin, flavin, and NADH binding domains.
      The position of the ferredoxin domain relative to the other two domains
      represents a new configuration for the iron-sulfur flavoprotein family. Close
      contacts between the C8 methyl group of FAD and [2Fe-2S] ligand Cys36-O represent
      a plausible pathway for electron transfer between the redox cofactors. Energy
      minimized docking of NADH and calculation of hingelike motions between domains
      suggest how simple coordinated shifts of residues at the C-terminus of the enzyme
      could expose the N5 position of FAD for productive interaction with the
      nicotinamide ring. The domain configuration revealed by the T4moF structure
      provides an excellent steric and electrostatic match to the obligate electron
      acceptor, Rieske-type [2Fe-2S] ferredoxin T4moC. Protein-protein docking and
      energy minimization of the T4moFC complex indicate that T4moF [2Fe-2S] ligand
      Cys41 and T4moC [2Fe-2S] ligand His67, along with other electrostatic
      interactions between the protein partners, form the functional electron transfer
      interface. 

PMID- 26309237
TI  - Analysis of phylogeny and codon usage bias and relationship of GC content, amino
      acid composition with expression of the structural nif genes.
AB  - Bacteria and archaea have evolved with the ability to fix atmospheric dinitrogen
      in the form of ammonia, catalyzed by the nitrogenase enzyme complex which
      comprises three structural genes nifK, nifD and nifH. The nifK and nifD encodes
      for the beta and alpha subunits, respectively, of component 1, while nifH encodes
      for component 2 of nitrogenase. Phylogeny based on nifDHK have indicated that
      Cyanobacteria is closer to Proteobacteria alpha and gamma but not supported by
      the tree based on 16SrRNA. The evolutionary ancestor for the different trees was
      also different. The GC1 and GC2% analysis showed more consistency than GC3% which
      appeared to below for Firmicutes, Cyanobacteria and Euarchaeota while highest in
      Proteobacteria beta and clearly showed the proportional effect on the codon usage
      with a few exceptions. Few genes from Firmicutes, Euryarchaeota, Proteobacteria
      alpha and delta were found under mutational pressure. These nif genes with low
      and high GC3% from different classes of organisms showed similar expected number
      of codons. Distribution of the genes and codons, based on codon usage
      demonstrated opposite pattern for different orientation of mirror plane when
      compared with each other. Overall our results provide a comprehensive analysis on
      the evolutionary relationship of the three structural nif genes, nifK, nifD and
      nifH, respectively, in the context of codon usage bias, GC content relationship
      and amino acid composition of the encoded proteins and exploration of crucial
      statistical method for the analysis of positive data with non-constant variance
      to identify the shape factors of codon adaptation index. 

PMID- 26309238
TI  - Transcriptional and posttranscriptional mechanisms contribute to the
      dysregulation of elastogenesis in Schimke immuno-osseous dysplasia.
AB  - BACKGROUND: Schimke immuno-osseous dysplasia (SIOD) is an autosomal recessive
      disorder caused by mutations in SMARCAL1. A frequent complication is
      arteriosclerosis associated with reduced elastin expression; however, the
      mechanism underlying the reduced elastin expression remains unknown. METHODS:
      Expression of transcriptional regulators of elastin (ELN) and microRNA (miRNA)
      regulators of ELN messenger RNA (mRNA), ELN promoter methylation, and ELN mRNA
      poly(A) tail length were assessed by quantitative RT-PCR, bisulfite Sanger
      sequencing, and the Poly(A) Tail Length Assay Kit, respectively, in unaffected
      developing human aortae and in an SIOD aorta. RESULTS: Comparing unaffected fetal
      and adult aortae, ELN precursor mRNA (pre-mRNA) levels remained nearly constant,
      whereas mRNA levels declined by ~10(2)-fold. This corresponded with a reduction
      in poly(A) tail length but not with changes in the other parameters. In contrast,
      compared to the unaffected fetal aortae, the SIOD aorta had 18-fold less ELN pre
      mRNA and 10(4)-fold less mRNA. This corresponded with increased expression of
      miRNA regulators and shorter ELN mRNA poly(A) tail lengths but not with altered
      expression of ELN transcriptional regulators or ELN promoter methylation.
      CONCLUSION: Posttranscriptional mechanisms account for the reduction in ELN mRNA
      levels in unaffected aortae, whereas transcriptional and posttranscriptional
      mechanisms reduce elastin expression in SIOD aorta and predispose to
      arteriosclerosis.

PMID- 26309239
TI  - Characterization of the Complete Mitochondrial Genome of Cerura menciana and
      Comparison with Other Lepidopteran Insects.
AB  - The complete mitochondrial genome (mitogenome) of Cerura menciana (Lepidoptera:
      Notodontidae) was sequenced and analyzed in this study. The mitogenome is a
      circular molecule of 15,369 bp, containing 13 protein-coding genes (PCGs), two
      ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes and a A+T-rich region.
      The positive AT skew (0.031) indicated that more As than Ts were present. All
      PCGs were initiated by ATN codons, except for the cytochrome c oxidase subunit 1
      (cox1) gene, which was initiated by CAG. Two of the 13 PCGs contained the
      incomplete termination codon T or TA, while the others were terminated with the
      stop codon TAA. The A+T-rich region was 372 bp in length and consisted of an
      'ATAGA' motif followed by an 18 bp poly-T stretch, a microsatellite-like (AT)8
      and a poly-A element upstream of the trnM gene. Results examining codon usage
      indicated that Asn, Ile, Leu2, Lys, Tyr and Phe were the six most frequently
      occurring amino acids, while Cys was the rarest. Phylogenetic relationships,
      analyzed based on the nucleotide sequences of the 13 PCGs from other insect
      mitogenomes, confirmed that C. menciana belongs to the Notodontidae family. 

PMID- 26309240
TI  - A systematic review of the cost and cost effectiveness of using standard oral
      nutritional supplements in community and care home settings.
AB  - BACKGROUND & AIMS: Despite the clinical benefits of using standard (non-disease
      specific) oral nutritional supplements (ONS) in the community and care homes,
      there is uncertainty about their economic consequences. METHODS: A systematic
      review was undertaken according to recommended procedures to assess whether ONS
      can produce cost savings and cost-effective outcomes. RESULTS: 19 publications
      with and without a hospital component were identified: 9 full text papers, 9
      abstracts, and 1 report with retrospective analyses of 6 randomised controlled
      trials. From these publications a total of 31 cost and 4 cost-effectiveness
      analyses were identified. Most were retrospective analyses based on clinical data
      from randomised controlled trials (RCTs). In 9 studies/economic models involving
      ONS use for <3 months, there were consistent cost savings compared to the control
      group (median cost saving 9.2%; P < 0.01). When used for >=3 months, the median
      cost saving was 5% (P > 0.05; 5 studies). In RCTs, ONS accounted for less than 5%
      of the total costs and the investment in the community produced a cost saving in
      hospital. Meta-analysis indicated that ONS reduced hospitalisation significantly
      (16.5%; P < 0.001; 9 comparisons) and mortality non-significantly (Relative risk
      0.86 (95% CI, 0.61, 1.22); 8 comparisons). Many clinically relevant outcomes
      favouring ONS were reported: improved quality of life, reduced infections,
      reduced minor post-operative complications, reduced falls, and functional
      limitations. Of the cost-effectiveness analyses involving quality adjusted life
      years or functional limitations, most favoured the ONS group. The care home
      studies (4 cost analyses; 2 cost-effectiveness analyses) had differing aims,
      designs and conclusions. CONCLUSIONS: Overall, the reviewed studies, mostly based
      on retrospective cost analyses, indicate that ONS use in the community produce an
      overall cost advantage or near neutral balance, often in association with
      clinically relevant outcomes, suggesting cost effectiveness. There is a need for
      prospective studies designed to examine primary economic outcomes.

PMID- 26309241
TI  - Relative Age in School and Suicide among Young Individuals in Japan: A Regression
      Discontinuity Approach.
AB  - OBJECTIVE: Evidence collected in many parts of the world suggests that, compared
      to older students, students who are relatively younger at school entry tend to
      have worse academic performance and lower levels of income. This study examined
      how relative age in a grade affects suicide rates of adolescents and young adults
      between 15 and 25 years of age using data from Japan. METHOD: We examined
      individual death records in the Vital Statistics of Japan from 1989 to 2010. In
      contrast to other countries, late entry to primary school is not allowed in
      Japan. We took advantage of the school entry cutoff date to implement a
      regression discontinuity (RD) design, assuming that the timing of births around
      the school entry cutoff date was randomly determined and therefore that
      individuals who were born just before and after the cutoff date have similar
      baseline characteristics. RESULTS: We found that those who were born right before
      the school cutoff day and thus youngest in their cohort have higher mortality
      rates by suicide, compared to their peers who were born right after the cutoff
      date and thus older. We also found that those with relative age disadvantage tend
      to follow a different career path than those with relative age advantage, which
      may explain their higher suicide mortality rates. CONCLUSION: Relative age
      effects have broader consequences than was previously supposed. This study
      suggests that policy intervention that alleviates the relative age effect can be
      important.

PMID- 26309242
TI  - Bisphenol A, Bisphenol S, and 4-Hydroxyphenyl 4-Isoprooxyphenylsulfone (BPSIP) in
      Urine and Blood of Cashiers.
AB  - BACKGROUND: Bisphenol A (BPA) is a high-production-volume chemical associated
      with a wide range of health outcomes in animal and human studies. BPA is used as
      a developer in thermal paper products, including cash register receipt paper;
      however, little is known about exposure of cashiers to BPA and alternative
      compounds in receipt paper. OBJECTIVE: We determined whether handling receipt
      paper results in measurable absorption of BPA or the BPA alternatives bisphenol S
      (BPS) and 4-hydroxyphenyl 4-isoprooxyphenylsulfone (BPSIP). METHODS: Cashiers (n
      = 77) and non-cashiers (n = 25) were recruited from the Raleigh-Durham-Chapel
      Hill region of North Carolina during 2011-2013. Receipts were analyzed for the
      presence of BPA or alternatives considered for use in thermal paper. In cashiers,
      total urine and serum BPA, BPS, and BPSIP levels in post-shift samples (collected
      <= 2 hr after completing a shift) were compared with pre-shift samples. Levels of
      these compounds in urine from cashiers were compared to levels in urine from non
      cashiers. RESULTS: Each receipt contained 1-2% by weight of the paper of BPA,
      BPS, or BPSIP. The post-shift geometric mean total urinary BPS concentration was
      significantly higher than the pre-shift mean in 33 cashiers who handled receipts
      containing BPS. The mean urine BPA concentrations in 31 cashiers who handled BPA
      receipts were as likely to decrease as to increase after a shift, but the mean
      post-shift concentrations were significantly higher than those in non-cashiers.
      BPSIP was detected more frequently in the urine of cashiers handling BPSIP
      receipts than in the urine of non-cashiers. Only a few cashiers had detectable
      levels of total BPA or BPS in serum, whereas BPSIP tended to be detected more
      frequently. CONCLUSIONS: Thermal receipt paper is a potential source of
      occupational exposure to BPA, BPS, and BPSIP. CITATION: Thayer KA, Taylor KW,
      Garantziotis S, Schurman SH, Kissling GE, Hunt D, Herbert B, Church R, Jankowich
      R, Churchwell MI, Scheri RC, Birnbaum LS, Bucher JR. 2016. Bisphenol A, bisphenol
      S, and 4-hydroxyphenyl 4-isoprooxyphenylsulfone (BPSIP) in urine and blood of
      cashiers. Environ Health Perspect 124:437-444;
      http://dx.doi.org/10.1289/ehp.1409427.

PMID- 26309243
TI  - Kasabach-Merritt phenomenon in Chinese children: Report of 19 cases and brief
      review of literature.
AB  - Kasabach-Merritt phenomenon (KMP) is life-threatening, charactered by the
      profound thrombocytopenia and consumptive coagulopathy associated with vascular
      tumors. The therapy of KMP still remains challenging. In this study, we
      retrospectively analyzed the clinical data of KMP treated in Nanjing Children's
      Hospital and Jinling Hospital, China, and brief reviewed the literature on KMP.
      From Jan. 2005 to Dec. 2014, a total of 19 cases of KMP were enrolled into this
      study. Laboratory results showed that seven patients had typical disseminated
      intravascular coagulation (DIC), and others were atypical DIC. CT scanning showed
      the low-density tumor with obvious intensification in enhanced scanning, and the
      large distorted arteries in association with the tumor. After the admission, the
      patients received the infusion of platelets and the applying of dipyridamole,
      steroids, and other necessary drugs. Eight patients underwent complete surgical
      removal of the tumor, or partial removal with subsequent chemotherapy of
      vincristine. Three patients underwent only the chemotherapy of vincristine. Eight
      patients underwent the intralesional injection of absolute ethanol. Pathological
      examination showed eighteen samples were kaposiform hemangioendothelioma, and one
      tufted agioma. In our cases, six patients died from extensive hemorrhage and
      subsequent multiple organ failure. The others survived. In conclusion, KMP in
      Chinese children has typical symptoms. Kaposiform hemangioendothelioma is the
      most frequent vascular tumor associated with KMP. The individual treatments with
      surgical management, chemotherapy with vincristine, and intralesional injection
      of absolute ethanol can achieve good results in most of the patients with KMP. 

PMID- 26309244
TI  - Feeding and Swallowing Disorders in Esophageal Atresia Patients: A Review of a
      Critical Issue.
AB  - Feeding and swallowing disorders are commonly seen in clinical practice in
      infants and children treated for esophageal atresia with or without
      tracheoesophageal fistula. Nevertheless, only few authors have addressed these
      issues. This review aims to describe the feeding and swallowing disorders
      encountered, focusing on pathophysiology, normal development of swallowing and
      feeding abilities, and possible rehabilitation therapies to prevent or correct
      these disorders. 

PMID- 26309245
TI  - Dysphagia in Children with Esophageal Atresia: Current Diagnostic Options.
AB  - Dysphagia or swallowing disorder is very common (range, 15-52%) in patients with
      esophageal atresia. Children present with a wide range of symptoms. The most
      common diagnostic tools to evaluate esophageal dysphagia, such as upper barium
      study and manometry, aim to characterize anatomy and function of the esophageal
      body and the esophagogastric junction (EGJ). Using these technologies, a variety
      of pathological motor patterns have been identified in children with esophageal
      atresia. However, the most challenging part of diagnosing patients with
      esophageal dysphagia lies in the fact that these methods fail to link functional
      symptoms such as dysphagia with the esophageal motor disorders observed. A recent
      method, called pressure-flow analysis (PFA), uses simultaneously acquired
      impedance and manometry measurements, and applies an integrated analysis of these
      recordings to derive quantitative pressure-flow metrics. These pressure-flow
      metrics allow detection of the interplay between bolus flow, motor patterns, and
      symptomatology by combining data on bolus transit and bolus flow resistance.
      Based on a dichotomous categorization, flow resistance at the EGJ and ineffective
      esophageal bolus transit can be determined. This method has the potential to
      guide therapeutic decisions for esophageal dysmotility in pediatric patients with
      esophageal atresia. 

PMID- 26309246
TI  - Ultrasonic Vocalizations of Male Mice Differ among Species and Females Show
      Assortative Preferences for Male Calls.
AB  - Male house mice (Mus musculus) emit ultrasonic vocalizations (USVs) during
      courtship, which attract females, and we aimed to test whether females use these
      vocalizations for species or subspecies recognition of potential mates. We
      recorded courtship USVs of males from different Mus species, Mus musculus
      subspecies, and populations (F1 offspring of wild-caught Mus musculus musculus,
      Mus musculus domesticus (and F1 hybrid crosses), and Mus spicilegus), and we
      conducted playback experiments to measure female preferences for male USVs. Male
      vocalizations contained at least seven distinct syllable types, whose frequency
      of occurrence varied among species, subspecies, and populations. Detailed
      analyses of multiple common syllable types indicated that Mus musculus and Mus
      spicilegus could be discriminated based on spectral and temporal characteristics
      of their vocalizations, and populations of Mus musculus were also distinctive
      regardless of the classification model used. Females were able to discriminate
      USVs from different species, and showed assortative preferences for conspecific
      males. We found no evidence that females discriminate USVs of males from a
      different subspecies or separate populations of the same species, even though our
      spectral analyses identified acoustic features that differ between species,
      subspecies, and populations of the same species. Our results provide the first
      comparison of USVs between Mus species or between Mus musculus subspecies, and
      the first evidence that male USVs potentially facilitate species recognition. 

PMID- 26309247
TI  - Enabling Low Cost Biopharmaceuticals: A Systematic Approach to Delete Proteases
      from a Well-Known Protein Production Host Trichoderma reesei.
AB  - The filamentous fungus Trichoderma reesei has tremendous capability to secrete
      proteins. Therefore, it would be an excellent host for producing high levels of
      therapeutic proteins at low cost. Developing a filamentous fungus to produce
      sensitive therapeutic proteins requires that protease secretion is drastically
      reduced. We have identified 13 major secreted proteases that are related to
      degradation of therapeutic antibodies, interferon alpha 2b, and insulin like
      growth factor. The major proteases observed were aspartic, glutamic, subtilisin
      like, and trypsin-like proteases. The seven most problematic proteases were
      sequentially removed from a strain to develop it for producing therapeutic
      proteins. After this the protease activity in the supernatant was dramatically
      reduced down to 4% of the original level based upon a casein substrate. When
      antibody was incubated in the six protease deletion strain supernatant, the heavy
      chain remained fully intact and no degradation products were observed. Interferon
      alpha 2b and insulin like growth factor were less stable in the same supernatant,
      but full length proteins remained when incubated overnight, in contrast to the
      original strain. As additional benefits, the multiple protease deletions have led
      to faster strain growth and higher levels of total protein in the culture
      supernatant. 

PMID- 26309249
TI  - Correction: Crystal Structure of Hcp from Acinetobacter baumannii: A Component of
      the Type VI Secretion System.

PMID- 26309248
TI  - Development of a Novel Method for Analyzing Pseudomonas aeruginosa Twitching
      Motility and Its Application to Define the AmrZ Regulon.
AB  - Twitching motility is an important migration mechanism for the Gram-negative
      bacterium Pseudomonas aeruginosa. In the commonly used subsurface twitching
      assay, the sub-population of P. aeruginosa with active twitching motility is
      difficult to harvest for high-throughput studies. Here we describe the
      development of a novel method that allows efficient isolation of bacterial sub
      populations conducting highly active twitching motility. The transcription factor
      AmrZ regulates multiple P. aeruginosa virulence factors including twitching
      motility, yet the mechanism of this activation remains unclear. We therefore set
      out to understand this mechanism by defining the AmrZ regulon using DNA
      microarrays in combination with the newly developed twitching motility method. We
      discovered 112 genes in the AmrZ regulon and many encode virulence factors. One
      gene of interest and the subsequent focus was lecB, which encodes a fucose
      binding lectin. DNA binding assays revealed that AmrZ activates lecB
      transcription by directly binding to its promoter. The lecB gene was previously
      shown to be required for twitching motility in P. aeruginosa strain PAK; however,
      our lecB deletion had no effect on twitching motility in strain PAO1.
      Collectively, in this study a novel condition was developed for quantitative
      studies of twitching motility, under which the AmrZ regulon was defined. 

PMID- 26309250
TI  - Potato virus Y HC-Pro Reduces the ATPase Activity of NtMinD, Which Results in
      Enlarged Chloroplasts in HC-Pro Transgenic Tobacco.
AB  - Potato virus Y (PVY) is an important plant virus and causes great losses every
      year. Viral infection often leads to abnormal chloroplasts. The first step of
      chloroplast division is the formation of FtsZ ring (Z-ring), and the placement of
      Z-ring is coordinated by the Min system in both bacteria and plants. In our lab,
      the helper-component proteinase (HC-Pro) of PVY was previously found to interact
      with the chloroplast division protein NtMinD through a yeast two-hybrid screening
      assay and a bimolecular fluorescence complementation (BiFC) assay in vivo. Here,
      we further investigated the biological significance of the NtMinD/HC-Pro
      interaction. We purified the NtMinD and HC-Pro proteins using a prokaryotic
      protein purification system and tested the effect of HC-Pro on the ATPase
      activity of NtMinD in vitro. We found that the ATPase activity of NtMinD was
      reduced in the presence of HC-Pro. In addition, another important chloroplast
      division related protein, NtMinE, was cloned from the cDNA of Nicotiana tabacum.
      And the NtMinD/NtMinE interaction site was mapped to the C-terminus of NtMinD,
      which overlaps the NtMinD/HC-Pro interaction site. Yeast three-hybrid assay
      demonstrated that HC-Pro competes with NtMinE for binding to NtMinD. HC-Pro was
      previously reported to accumulate in the chloroplasts of PVY-infected tobacco and
      we confirmed this result in our present work. The NtMinD/NtMinE interaction is
      very important in the regulation of chloroplast division. To demonstrate the
      influence of HC-Pro on chloroplast division, we generated HC-Pro transgenic
      tobacco with a transit peptide to retarget HC-Pro to the chloroplasts. The HC-Pro
      transgenic plants showed enlarged chloroplasts. Our present study demonstrated
      that the interaction between HC-Pro and NtMinD interfered with the function of
      NtMinD in chloroplast division, which results in enlarged chloroplasts in HC-Pro
      transgenic tobacco. The HC-Pro/NtMinD interaction may cause the formation of
      abnormal chloroplasts in PVY-infected plants. 

PMID- 26309251
TI  - Highly and Broad-Spectrum In Vitro Antitumor Active cis-Dichloridoplatinum(II)
      Complexes with 7-Azaindoles.
AB  - The cis-[PtCl2(naza)2] complexes (1-3) containing monosubstituted 7-azaindole
      halogeno-derivatives (naza), showed significantly higher activity than cisplatin
      towards ovarian carcinoma A2780, its cisplatin-resistant variant A2780R,
      osteosarcoma HOS, breast carcinoma MCF7 and cervix carcinoma HeLa cell lines,
      with the IC50 values of 3.8, 3.5, 4.5, 2.7, and 9.2 MUM, respectively, obtained
      for the most active complex 3. As for 4 and 5 having disubstituted 7-azaindoles
      in their molecule, the significant cytotoxicity was detected only for 4 against
      A2780 (IC50 = 4.8 MUM), A2780R (IC50 = 3.8 MUM) and HOS (IC50 = 4.3 MUM), while 5
      was evaluated as having only moderate antiproliferative effect against the
      mentioned cancer cell lines with IC50 = 33.4, 24.7 and 46.7 MUM, respectively.
      All the studied complexes 1-5 effectively avoided the acquired resistance of
      ovarian carcinoma cell line. On the other hand, the complexes did not reveal any
      inhibition activity on the purified 20S proteasome from the A2780 cells. The
      representative complexes 3 and 5 showed low ability to be hydrolysed, but their
      stability was markedly lowered in the presence of physiological sulphur
      containing biomolecule glutathione (GSH), as proved by the 1H NMR spectroscopy
      and mass spectrometry studies. A rate of interaction of the studied complexes
      with GSH was affected by an addition of another mechanistically relevant
      biomolecule guanosine monophosphate. The differences in interactions of 3 and 5
      with GSH correlate well with their different cytotoxicity profiles. 

PMID- 26309252
TI  - Markedly Divergent Tree Assemblage Responses to Tropical Forest Loss and
      Fragmentation across a Strong Seasonality Gradient.
AB  - We examine the effects of forest fragmentation on the structure and composition
      of tree assemblages within three seasonal and aseasonal forest types of southern
      Brazil, including evergreen, Araucaria, and deciduous forests. We sampled three
      southernmost Atlantic Forest landscapes, including the largest continuous forest
      protected areas within each forest type. Tree assemblages in each forest type
      were sampled within 10 plots of 0.1 ha in both continuous forests and 10 adjacent
      forest fragments. All trees within each plot were assigned to trait categories
      describing their regeneration strategy, vertical stratification, seed-dispersal
      mode, seed size, and wood density. We detected differences among both forest
      types and landscape contexts in terms of overall tree species richness, and the
      density and species richness of different functional groups in terms of
      regeneration strategy, seed dispersal mode and woody density. Overall, evergreen
      forest fragments exhibited the largest deviations from continuous forest plots in
      assemblage structure. Evergreen, Araucaria and deciduous forests diverge in the
      functional composition of tree floras, particularly in relation to regeneration
      strategy and stress tolerance. By supporting a more diversified light-demanding
      and stress-tolerant flora with reduced richness and abundance of shade-tolerant,
      old-growth species, both deciduous and Araucaria forest tree assemblages are more
      intrinsically resilient to contemporary human-disturbances, including
      fragmentation-induced edge effects, in terms of species erosion and functional
      shifts. We suggest that these intrinsic differences in the direction and
      magnitude of responses to changes in landscape structure between forest types
      should guide a wide range of conservation strategies in restoring fragmented
      tropical forest landscapes worldwide. 

PMID- 26309253
TI  - Positive Association between APOA5 rs662799 Polymorphism and Coronary Heart
      Disease: A Case-Control Study and Meta-Analysis.
AB  - OBJECTIVE: Apolipoprotein A5 (APOA5) is associated with plasma triglyceride (TG)
      levels, a risk factor for coronary heart disease (CHD). This study explored the
      association between CHD and the APOA5 rs662799 polymorphism. METHODS: We
      collected 1,521 samples (783 CHD patients and 738 controls) for this case-control
      study. Meta-analysis was performed using Review Manager Software and Stata
      Software. RESULTS: Significant differences were observed between CHD cases and
      controls at the level of both genotype (chi2 = 8.964, df = 2, P = 0.011) and
      allele (chi2 = 9.180, df = 1, P = 0.002, OR = 1.275, 95% CI = 1.089-1.492). A
      breakdown analysis by gender showed a significant association of APOA5 rs662799
      with CHD in males (chi2 = 7.770, df = 1, P = 0.005; OR = 1.331, 95% CI = 1.088
      1.628). An additional meta-analysis using 21378 cases and 28428 controls
      established that rs662799 is significantly associated with CHD (P < 0.00001).
      CONCLUSION: Both our case-control study and meta-analysis confirm a significant
      association between APOA5 rs662799 and CHD. In addition, our results suggest a
      male-specific association between the APOA5 rs662799 polymorphism and CHD.

PMID- 26309254
TI  - Pain in Parkinson's Disease: A Cross-Sectional Study of Its Prevalence, Types,
      and Relationship to Depression and Quality of Life.
AB  - Pain is an important and distressing symptom in Parkinson's disease (PD). Our aim
      was to determine the prevalence of pain, its various types and characteristics,
      as well as its impact on depression and quality of life (QoL) in patients with
      PD. How pain differs in early- and advanced-stage PD and male and female PD
      patients was of special interest. One hundred PD patients on dopaminergic
      medications had a neurological examination and participated in a structured
      interview on pain characteristics and completed standardized questionnaires. A
      total of 76% of the patients had pain. The following types of pain were present:
      musculoskeletal pain accounted for 41% of the total pain, dystonic pain for 17%,
      central neuropathic pain for 22%, radicular pain for 27%, and other pains (non
      radicular low back pain, arthritic, and visceral pain) made up 24%. One type of
      pain affected 29% of all the subjects, two types 35%, three types 10%, and four
      types of pain were reported by 2%. All types of pain were more prevalent in
      advanced-stage PD subjects than in early-stage PD subjects, except for arthritic
      pain (subclassified under"other pain"). The frequency and intensity of actual,
      average, and worst experienced pain were significantly more severe in advanced
      stage subjects. PD subjects with general pain and in advanced stages were more
      depressed and had poorer QoL. Depression correlated with worst pain in the last
      24 hours and with pain periodicity (the worst depression score in patients with
      constant pain). QoL correlated with average pain in the last 7 days. Pain is a
      frequent problem in PD patients, and it worsens during the course of the disease.

PMID- 26309255
TI  - A New Epigenetic Mechanism of Temozolomide Action in Glioma Cells.
AB  - Temozolomide (TMZ) is an oral alkylating chemotherapeutic agent that prolongs the
      survival of patients with glioblastoma (GBM). Despite that high TMZ potential,
      progression of disease and recurrence are still observed. Therefore a better
      understanding of the mechanism of action of this drug is necessary and may allow
      more durable benefit from its anti-glioma properties. Using nucleotide post
      labelling method and separation on thin-layer chromatography we measured of
      global changes of 5-methylcytosine (m5C) in DNA of glioma cells treated with TMZ.
      Although m5C is not a product of TMZ methylation reaction of DNA, we analysed the
      effects of the drug action on different glioma cell lines through global changes
      at the level of the DNA main epigenetic mark. The first effect of TMZ action we
      observed is DNA hypermethylation followed by global demethylation. Therefore an
      increase of DNA methylation and down regulation of some genes expression can be
      ascribed to activation of DNA methyltransferases (DNMTs). On the other hand
      hypomethylation is induced by oxidative stress and causes uncontrolled expression
      of pathologic protein genes. The results of brain tumours treatment with TMZ
      suggest the new mechanism of modulation epigenetic marker in cancer cells. A high
      TMZ concentration induced a significant increase of m5C content in DNA in the
      short time, but a low TMZ concentration at longer time hypomethylation is
      observed for whole range of TMZ concentrations. Therefore TMZ administration with
      low doses of the drug and short time should be considered as optimal therapy. 

PMID- 26309256
TI  - Length Is Associated with Pain: Jellyfish with Painful Sting Have Longer
      Nematocyst Tubules than Harmless Jellyfish.
AB  - A large number of humans are stung by jellyfish all over the world. The stings
      cause acute pain followed by persistent pain and local inflammation. Harmful
      jellyfish species typically cause strong pain, whereas harmless jellyfish cause
      subtle or no pain. Jellyfish sting humans by injecting a tubule, contained in the
      nematocyst, the stinging organ of jellyfish. The tubule penetrates into the skin
      leading to venom injection. The detailed morphology of the nematocyst tubule and
      molecular structure of the venom in the nematocyst has been reported; however,
      the mechanism responsible for the difference in pain that is caused by harmful
      and harmless jellyfish sting has not yet been explored or explained. Therefore,
      we hypothesized that differences in the length of the nematocyst tubule leads to
      different degrees of epithelial damage. The initial acute pain might be generated
      by penetration of the tubule, which stimulates pain receptor neurons, whilst
      persistent pain might be caused by injection of venom into the epithelium. To
      test this hypothesis we compared the lengths of discharged nematocyst tubules
      from harmful and harmless jellyfish species and evaluated their ability to
      penetrate human skin. The results showed that the harmful jellyfish species,
      Chrysaora pacifica, Carybdea brevipedalia, and Chironex yamaguchii, causing
      moderate to severe pain, have nematocyst tubules longer than 200 MUm, compared
      with a jellyfish species that cause little or no pain, Aurelia aurita. The
      majority of the tubules of harmful jellyfishes, C. yamaguchii and C.
      brevipedalia, were sufficiently long to penetrate the human epidermis and
      physically stimulate the free nerve endings of Adelta pain receptor fibers around
      plexuses to cause acute pain and inject the venom into the human skin epithelium
      to cause persistent pain and inflammation. 

PMID- 26309257
TI  - Snf1 Phosphorylates Adenylate Cyclase and Negatively Regulates Protein Kinase A
      dependent Transcription in Saccharomyces cerevisiae.
AB  - In eukaryotes, nutrient availability and metabolism are coordinated by sensing
      mechanisms and signaling pathways, which influence a broad set of cellular
      functions such as transcription and metabolic pathways to match environmental
      conditions. In yeast, PKA is activated in the presence of high glucose
      concentrations, favoring fast nutrient utilization, shutting down stress
      responses, and boosting growth. On the contrary, Snf1/AMPK is activated in the
      presence of low glucose or alternative carbon sources, thus promoting an energy
      saving program through transcriptional activation and phosphorylation of
      metabolic enzymes. The PKA and Snf1/AMPK pathways share common downstream
      targets. Moreover, PKA has been reported to negatively influence the activation
      of Snf1/AMPK. We report a new cross-talk mechanism with a Snf1-dependent
      regulation of the PKA pathway. We show that Snf1 and adenylate cyclase (Cyr1)
      interact in a nutrient-independent manner. Moreover, we identify Cyr1 as a Snf1
      substrate and show that Snf1 activation state influences Cyr1 phosphorylation
      pattern, cAMP intracellular levels, and PKA-dependent transcription.

PMID- 26309258
TI  - Arrhythmogenic Calmodulin Mutations Affect the Activation and Termination of
      Cardiac Ryanodine Receptor-mediated Ca2+ Release.
AB  - The intracellular Ca(2+) sensor calmodulin (CaM) regulates the cardiac Ca(2+)
      release channel/ryanodine receptor 2 (RyR2), and mutations in CaM cause
      arrhythmias such as catecholaminergic polymorphic ventricular tachycardia (CPVT)
      and long QT syndrome. Here, we investigated the effect of CaM mutations causing
      CPVT (N53I), long QT syndrome (D95V and D129G), or both (CaM N97S) on RyR2
      mediated Ca(2+) release. All mutations increased Ca(2+) release and rendered RyR2
      more susceptible to store overload-induced Ca(2+) release (SOICR) by lowering the
      threshold of store Ca(2+) content at which SOICR occurred and the threshold at
      which SOICR terminated. To obtain mechanistic insights, we investigated the
      Ca(2+) binding of the N- and C-terminal domains (N- and C-domain) of CaM in the
      presence of a peptide corresponding to the CaM-binding domain of RyR2. The N53I
      mutation decreased the affinity of Ca(2+) binding to the N-domain of CaM,
      relative to CaM WT, but did not affect the C-domain. Conversely, mutations N97S,
      D95V, and D129G had little or no effect on Ca(2+) binding to the N-domain but
      markedly decreased the affinity of the C-domain for Ca(2+). These results suggest
      that mutations D95V, N97S, and D129G alter the interaction between CaM and the
      CaMBD and thus RyR2 regulation. Because the N53I mutation minimally affected
      Ca(2+) binding to the C-domain, it must cause aberrant regulation via a different
      mechanism. These results support aberrant RyR2 regulation as the disease
      mechanism for CPVT associated with CaM mutations and shows that CaM mutations not
      associated with CPVT can also affect RyR2. A model for the CaM-RyR2 interaction,
      where the Ca(2+)-saturated C-domain is constitutively bound to RyR2 and the N
      domain senses increases in Ca(2+) concentration, is proposed. 

PMID- 26309259
TI  - Interactive Effects of Southern Rice Black-Streaked Dwarf Virus Infection of Host
      Plant and Vector on Performance of the Vector, Sogatella furcifera (Homoptera:
      Delphacidae).
AB  - Performance of insect vectors can be influenced by the viruses they transmit,
      either directly by infection of the vectors or indirectly via infection of the
      host plants. Southern rice black-streaked dwarf virus (SRBSDV) is a propagative
      virus transmitted by the white-backed planthopper, Sogatella furcifera (Hovath).
      To elucidate the influence of SRBSDV on the performance of white-backed
      planthopper, life parameters of viruliferous and nonviruliferous white-backed
      planthopper fed rice seedlings infected or noninfected with SRBSDV were measured
      using a factorial design. Regardless of the infection status of the rice plant
      host, viruliferous white-backed planthopper nymphs took longer to develop from
      nymph to adult than did nonviruliferous nymphs. Viruliferous white-backed
      planthopper females deposited fewer eggs than nonviruliferous females and both
      viruliferous and nonviruliferous white-backed planthopper females laid fewer eggs
      on infected than on noninfected plants. Longevity of white-backed planthopper
      females was also affected by the infection status of the rice plant and white
      backed planthopper. Nonviruliferous white-backed planthopper females that fed on
      infected rice plants lived longer than the other three treatment groups. These
      results indicate that the performance of white-backed planthopper is affected by
      SRBSDV either directly (by infection of white-backed planthopper) or indirectly
      (by infection of rice plant). The extended development of viruliferous nymphs and
      the prolonged life span of nonviruliferous adults on infected plants may increase
      their likelihood of transmitting virus, which would increase virus spread.

PMID- 26309260
TI  - Development of Species-Specific Primers for Agronomical Thrips and Multiplex
      Assay for Quarantine Identification of Western Flower Thrips.
AB  - While morphological identification of thrips species has been difficult because
      of their minute size and a lack of easily recognizable characteristics, molecular
      identification based on the development of specific molecular markers can be
      easily and reliably carried out. Among the known molecular markers, the nuclear
      internal transcribed spacer (ITS) exhibits distinguishable variations among
      thrips species. In this study, sequences of ITS2 region of 10 agriculturally
      important thrips were established to design species-specific primers for
      polymerase chain reaction (PCR). ITS2 sequence variations within these species
      were far less than those among species, indicating the suitability of this marker
      for species-specific primers design. These primers, though with one or two
      sporadically variable positions, showed a good efficacy within species. The
      specificity of these primers, examined on thrips species belonging to 15 genera,
      proved satisfactory. Furthermore, a multiplex PCR was used successfully for
      identifying Frankliniella occidentalis (Pergande), an insect pest monitored for
      quarantine purpose, and three additional thrips also commonly found in imported
      agricultural products and field samples, i.e., Thrips tabaci Lindeman, Thrips
      hawaiiensis (Morgan), and Frankliniella intonsa (Trybom). This study has
      demonstrated that specific primers and multiplex PCR based on ITS2 are reliable,
      convenient, and diagnostic tool to discriminate thrips species of quarantine and
      agricultural importance.

PMID- 26309261
TI  - One Metarhizium brunneum Strain, Two Uses to Control Ceratitis capitata (Diptera:
      Tephritidae).
AB  - We determined the virulence and insecticidal activity of the hypocrealean fungus
      Metarhizium brunneum (Petch) strain EAMb 09/01-Su and its crude extract against
      Mediterranean fruit fly Ceratitis capitata Wiedemann (Diptera: Tephritidae) and
      we evaluated the combined use of the fungus with its crude extract. We also
      determined the effect of fermentation time, temperature, and initial pH of the M.
      brunneum culture medium on the insecticidal activity of the crude extract. When
      C. capitata adults were sprayed with a conidial suspension, the strain EAMb 09/01
      Su caused 100% mortality with a mean lethal time (LT50) of 5.6 d and mean lethal
      concentration (LC50) of 2.84 f#x2013; 10(7) conidia per milliliter. Fermentation
      time significantly affected the lethality of the crude extract when it was
      provided to C. capitata per os. The highest level of mortality (73.3%) and the
      shortest median survival time (25.5 h) was obtained from 15-d-old cultures. The
      crude extract was demonstrated to be thermostable, given that the mortality was
      >50% at 48 h when the extract had been heated to 100 degrees C for 3 h. Lastly,
      the optimum initial pH for maximum crude extract activity in terms of mortality
      ranged between 7 and 9. Additivity was observed for all M. brunneum EAMb 09/01-Su
      strain crude extract combinations tested, indicating compatibility between
      products. We concluded that the M. brunneum EAMb 09/01-Su strain is a promising
      tool for medfly control alone or in combination with its crude extract.

PMID- 26309262
TI  - Cold Tolerance of the Mediterranean Fruit Fly in Date and Mandarin.
AB  - The Mediterranean fruit fly, Ceratitis capitata (Wiedemann), is an endemic pest
      in Israel and there can be low levels of infestation of dates (Phoenix
      dactylifera L.). Because C. capitata is considered a quarantine pest by several
      major importing countries, the export of fresh dates requires the elimination of
      this pest. For mandarin, cold storage at 1.11 degrees C for 15 d is considered to
      be an effective treatment for the elimination of C. capitata. In this study, we
      compared the cold tolerance of C. capitata in "Barhi" dates to that of C.
      capitata in mandarins (Citrus unshiu Marcovitch, "Satsuma"). In Barhi dates, we
      found the third instars to be the most cold-tolerant as compared with other life
      stages. Ceratitis capitata in date fruits were significantly less cold-tolerant
      than C. capitata in Satsuma mandarins. The last viable larvae in dates and
      mandarins were found after 8 and 13 d of treatment, respectively, and the
      calculated mortality curves in the two crops were significantly different. These
      results demonstrate that C. capitata is more sensitive to cold treatment when in
      date fruits than in mandarins. Therefore, the quarantine cold treatments used to
      eliminate C. capitata from mandarins should be sufficiently effective if applied
      to fresh date fruits.

PMID- 26309263
TI  - Evaluation of the Host Status of Mature Green Papayas 'Maradol' for the Mexican
      Fruit Fly (Diptera: Tephritidae).
AB  - The suitability of mature green 'Maradol' papaya as a host of Anastrepha ludens
      (Loew) was studied under field and laboratory conditions. Field tests were
      conducted on commercial-ripened and spot-ripened fruit in two orchards and during
      two seasons in the state of Chiapas. Fruits at exportation ripeness are in
      "commercial ripeness", while fruits that are harvested immediately preceding
      exportation ripeness are in "spot ripeness." The field tests consisted of forced
      infestation experiments that evaluated papayas at two ripeness stages: the
      commercial- or exportation-ripened fruit (green fruits with one or two yellow
      stripes) and fruit before exportation ripeness called "spot ripeness." These
      tests were conducted in two orchards and during two seasons in the state of
      Chiapas, Mexico. Laboratory trials were performed with commercial-ripened fruit
      only. Fruit from four different postharvest periods (3, 24, 48, and 72 h) were
      exposed to groups of gravid flies. No larvae emerged from the fruit that was
      collected in the field experiments. However, some larvae and several fertile
      flies were obtained from the commercial-ripened fruit 72 h postharvest but not 3,
      24, and 48 h postharvest in the laboratory. The results of this study indicate
      that the commercially ripe fruits of papaya Maradol were resistant to or free
      from infestation of A. ludens flies under field conditions, though these fruits
      must be considered nonnatural, conditional host because they became infested in
      the laboratory.

PMID- 26309264
TI  - Effects of Solenopsis invicta (Hymenoptera: Formicidae) and Its Interaction With
      Aphids on the Seed Productions of Mungbean and Rapeseed Plants.
AB  - Although many reports suggested the economic importance of the red imported fire
      ant, Solenopsis invicta Buren, few attempts to test the hypothesis that the red
      imported fire ant-aphid mutualism enhances the occurrence of red imported fire
      ant on crops, thereby interfering with their flowering and fruiting and affecting
      their output. To address this problem, we compare the effects of red imported
      fire ant on the flowering and fruiting of self-pollinating and cross-pollinating
      crops by field investigations and indoor experiments. In the field, our results
      revealed that regardless of the aphid interaction, red imported fire ant
      preferred flowering mungbean plants, and their activities decreased the yields of
      single plants, total pod number, kernel number, and kernel weight. The
      interaction of red imported fire ant and aphids generated unfavorable effects on
      rapeseed yields per plant, total pod number, grain number, grain weight, and
      thousand-kernel weight and stimulated an elevated proportion of malformed seeds.
      However, the differences were not significant if only red imported fire ant was
      present. In the laboratory, although red imported fire ant display no apparent
      preference toward the seedlings of mungbean or rapeseed, the ants clearly favor
      the flowering plants of mungbeans. Therefore, this study indicated that one of
      the main mechanisms whereby red imported fire ants affect the crop yield is by
      compromising the reproduction processes.

PMID- 26309265
TI  - Life Table Parameters of Tuta absoluta (Lepidoptera: Gelechiidae) on Different
      Varieties of Tomato.
AB  - Tuta absoluta (Meyrick), a tomato leaf miner, is one of the destructive pests of
      tomatoes, which is native to South America, and has been considered as a
      quarantined pest for Iran since 2010 while it has quickly spread all around the
      country and is known as a key pest in tomato-cultured regions since 2012. In the
      current study, the life table parameters of T. absoluta were studied on cut
      leaves of three greenhouse cultivars of tomato including 'Atabay', 'Cluse', and
      'Perenses'. Data were analyzed based on the age-stage, two-sex life table
      analysis. Results showed differences in the duration of egg, larvae, pupae, and
      adults. Meanwhile, the life table parameters including intrinsic rate of increase
      (r), finite rate of increase (lambda), net reproductive rate (R0), and gross
      reproductive rate (GRR) were categorized increasingly based on the feeding on
      Cluse, Atabay, and Perenses, respectively. The findings of the current study
      showed that the Cluse could be nominated as an unsuitable host for tomato leaf
      miner among cultivars because of its negative influences on the pest's biological
      parameters. Moreover, these results may develop the finding and screening process
      of relatively resistant cultivars to be used in the management of T. absoluta.

PMID- 26309266
TI  - Factors Limiting Peach as a Potential Host for Drosophila suzukii (Diptera:
      Drosophilidae).
AB  - The spotted wing drosophila, Drosophila suzukii Matsumura, has widely established
      in North America and become an economic concern for a variety of fruit crops. To
      better understand fruit susceptibility, we evaluated peach surface
      characteristics on the pest's oviposition success. The number of D. suzukii eggs
      laid into the fruit flesh was tested on 1) peaches with or without indumenta
      (commonly referred to as peach fuzz), 2) peaches physically damaged by harvest
      operations, 3) peaches damaged by the peach twig borer Anarsia lineatella Zeller
      or the forktailed bush katydid, Scudderia furcata Brunner von Wattenwyl, and 4)
      peaches with punctures that simulated stink bug damage. Female D. suzukii did not
      lay eggs in intact fuzzy sections of the fruit or into small punctures (0.3 or
      0.5 mm), but readily laid eggs in sections without fuzz, with insect damage, and
      with large punctures (1 mm). The number of eggs per treatment was positively
      related to the area of the damaged section; the overall fruit firmness and sugar
      content was not related to the number of eggs laid in treated or damaged spots.
      Direct observations of D. suzukii oviposition confirmed that peach fuzz appeared
      to be an obstacle for the fly's oviposition success, and female flies ceased
      ovipositional attempts on fuzzy peach sections after a short period of time.
      Successful oviposition times were associated with substrate firmness, with
      shorter oviposition time in damaged spots than in cherry fruit or shaved spots of
      the peach. The results indicate that intact, preharvest peach fruit are unlikely
      to be infested by the fly, but any surface damage could render the fruit
      susceptible to the fly.

PMID- 26309267
TI  - Laboratory Colonization of the Blow Flies, Chrysomya megacephala (Diptera:
      Calliphoridae) and Chrysomya rufifacies (Diptera: Calliphoridae).
AB  - Chrysomya megacephala (F.) and Chrysomya rufifacies (Macquart) were colonized so
      that larval growth rates could be compared. Colonies were also established to
      provide insight into the protein needs of adult C. rufifacies and developmental
      rates of the ensuing larvae. The C. megacephala and C. rufifacies laboratory
      colonies were reared for five and six generations, respectively, at 28 degrees C.
      C. megacephala developmental mean rate from egg to adult was 20.4 +/- 0.38 d.
      First-instar larvae emerge in 1.4 +/- 0.24 d, second-instar larvae develop in 2.6
      +/- 0.38 d and third instars occur at 6.3 +/- 0.72 d. Development from egg to
      pupation occurred in 12 +/- 1.10 d. C. rufifacies developed at a mean rate of
      16.2 +/- 0.78 d from egg to adult emergence. Each stage occurred in succession
      from first-instar larvae 1.1 +/- 0.25 d, second-instar larvae developed 2.3 +/-
      0.25 d later, and the third-instar larvae developed 5.7 +/- 0.41 d later. The
      larvae pupated 10.0 +/- 0.57 d after oviposition. Both of these flies can be
      collected in the wild and easily colonized using conditioned chicken as an
      oviposition and larval medium. C. megacephala apparently prefers a lower
      development and maintenance temperature than C. rufifacies, as evidenced by the
      high pupal mortality. Laboratory-reared C. rufifacies benefited from bloodmeal as
      a protein supplement to enhance egg production. C. rufifacies larvae were not
      observed preying on each other and additional larval species were not provided to
      serve as prey.

PMID- 26309268
TI  - Effect of Food Deprivation Period on the Development and Reproduction of
      Riptortus pedestris (Hemiptera: Alydidae), and Its Egg Parasitism.
AB  - The bean bug, Riptortus pedestris (F.) (Hemiptera: Alydidae) is one of the most
      important pests of soybean (Glycine max L. Merrill) in Korea and Japan. R.
      pedestris is known to appear early in spring when leguminous seeds such as
      soybean are not available. Because soybean has been reported to be the most
      important food source for R. pedestris development, in this study, we assessed
      the effect of this period of soybean deprivation during the nymphal stage on the
      development and reproduction of R. pedestris and on egg parasitism by its two egg
      parasitoids. More than 50% of the R. pedestris population tested survived on
      barley, even when they did not start feeding on soybean until the fourth instar.
      Nevertheless, R. pedestris nymphs deprived of soybean developed more slowly and
      became smaller adults than those provided with soybean. However, no difference
      was observed in the preovipositional period or fecundity between these groups. In
      addition, neither the hatch nor the egg parasitism rate by two egg parasitoids
      was affected by the presence or absence of soybeans in the nymphal diet. This
      study indicates that R. pedestris nymphs can develop successfully even when
      lacking this important food source in early life, and that adult reproduction is
      not affected by the quality of diet ingested during the nymphal period.

PMID- 26309269
TI  - Phototaxis of Grapholitha molesta (Lepidoptera: Olethreutidae) to Different Light
      Sources.
AB  - The Oriental Fruit Moth Grapholita molesta (Busck) causes substantial damage to
      stone and pome fruit crops worldwide. Light-based traps offer a potential means
      for pest monitoring and management. In this study, we tested the preference of G.
      molesta for the following light sources: monochromatic light produced from light
      emitting diodes (LEDs) (red, orange, yellow, green, blue, violet, and white),
      specific wavelengths of light produced from filters (405, 450, 480, 512, 540,
      576, and 610 nm), and polychromatic light produced by different numbers (0, 12,
      24, and 36) of green, blue, and violet LEDs. The arrangement of polychromatic
      lights was based on an orthogonal design matrix of L16 (4(3)). Based on the
      results of former studies, we further determined the optimal number of green and
      violet LEDs. The results showed that: 1) G. molesta strongly preferred the green,
      violet, and blue LEDs; 2) G. molesta significantly preferred light at 405 nm,
      followed by 540 nm, and showed no phototaxis to 480 nm; 3) for the polychromatic
      light configuration, violet and green were the factors that determined the
      preference of G. molesta, and the lamp with 12 violet LEDs captured the most
      moths; and 4) for the lamps with different light intensities, 36 violet LEDs or
      12 green LEDs attracted the most moths, with the former performing better.

PMID- 26309270
TI  - myo-Inositol and Phytate Are Toxic to Formosan Subterranean Termites (Isoptera:
      Rhinotermitidae).
AB  - Several rare and common monosaccharides were screened for toxic effects on the
      Formosan subterranean termite, Coptotermes formosanus Shiraki, with the aim of
      identifying environmentally friendly termiticides. myo-Inositol and phytic acid,
      which are nontoxic to mammals, were identified as potential termite control
      compounds. Feeding bioassays with termite workers, where both compounds were
      supplied on filter paper in concentrations from 160.2 to 1,281.7 MUg/mm(3),
      showed concentration-dependent toxicity within 2 wk. Interestingly myo-inositol
      was nontoxic when administered to termites in agar (40 mg/ml) in the absence of a
      cellulosic food source, an unexplained phenomenon. In addition, decreased
      populations of termite hindgut protozoa were observed upon feeding on myo
      inositol but not phytate-spiked filter paper. Radiotracer feeding studies using
      myo-inositol-[2-(3)H] with worker termites showed no metabolism after ingestion
      over a 2-d feeding period, ruling out metabolites responsible for the selective
      toxicity.

PMID- 26309271
TI  - Exposure of Brown Recluse and Brown Widow Spiders (Araneae: Sicariidae,
      Theridiidae) to a Commercial Sulfuryl Fluoride Fumigation.
AB  - The body of pesticide research on spiders is sparse with most studies using
      topical or residual applications to assess efficacy. Data on the effects of
      fumigation on spider survivorship are scarce in the scientific literature. In
      this study, we exposed adult male and female brown recluse spiders, Loxosceles
      reclusa Gertsch & Mulaik, and female brown widow spiders, Latrodectus geometricus
      C. L. Koch, to a commercial fumigation event using sulfuryl fluoride directed at
      termite control. General consensus from the pest control industry is that
      fumigation is not always effective for control of spiders for a variety of
      reasons, including insufficient fumigant dosage, particularly, for contents of
      egg sacs that require a higher fumigant dosage for control. We demonstrated that
      a sulfuryl fluoride fumigation with an accumulated dosage of 162 oz-h per 1,000
      ft(3) at 21 degrees C over 25 h (~1.7 * the drywood termite dosage) directed at
      termites was sufficient to kill adult brown recluse and brown widow spiders. The
      effectiveness of commercial fumigation practices to control spiders, and
      particularly their egg sacs, warrants further study.

PMID- 26309272
TI  - Insect Damage, Aflatoxin Content, and Yield of Bt Corn in Alabama.
AB  - Isoline pairs of hybrid corn, similar except for presence or absence of a Bt
      trait, were planted at eight sites across Alabama over three years. This study
      evaluated insect damage, yield, and aflatoxin levels as affected by the Bt
      traits, YieldGard Corn Borer (expressing Cry1Ab), Herculex I (expressing Cry1F),
      Genuity VT Triple PRO (expressing Cry1A.105 and Cry2Ab2), Agrisure Viptera 3111
      (expressing Vip3Aa20 and Cry1Ab), and Genuity SmartStax (expressing Cry1A.105,
      Cry2Ab2, and Cry1F). When examined over all sites and years, hybrids with any of
      the included Bt traits had lower insect damage and higher yields. However, insect
      damage was not consistently correlated to yield. Bt traits expressing multiple
      proteins provided greater protection from corn earworm feeding than did traits
      for single proteins. Yields and aflatoxin levels were highly variable among sites
      although irrigated sites had higher yields than nonirrigated sites. Aflatoxins
      commonly accumulate in corn in the southeastern United States because of
      prevailing high temperatures and frequent dry conditions. Aflatoxin levels were
      not consistently associated with any factors that were evaluated, including Bt
      traits.

PMID- 26309273
TI  - Mating Disruption or Mass Trapping, Compared With Chemical Insecticides, for
      Suppression of Chilo suppressalis (Lepidoptera: Crambidae) in Northeastern China.
AB  - Asiatic rice borer, Chilo suppressalis (Walker), larvae cause extensive crop
      losses worldwide. Because chemical control is problematic, and sex pheromone
      applications are a valuable management tactic in China, judicious timing of a
      minimal density of pheromone dispensers is important in developing a cost
      effective C. suppressalis IPM program. During June-October in 2011, 20, 30, 40,
      and 50 dispensers per hectare for mass trapping, and 200, 300, 400, and 500
      dispensers per hectare for mating disruption were placed in northeastern China
      rice fields. Based on those results, only the two highest mass trapping densities
      were used in 2012-2013. The 40, 50, and 500 dispenser densities reduced egg
      masses to <2.0 per 100 tillers, compared with >9.5 in the insecticide-treated
      plots in 2011-2013. The reduced oviposition resulted in >85% reduction of larval
      damage, which was comparable with the currently used insecticides, dimethoate and
      deltamethrin (0.35 kg/ha), which gave no egg reduction, but ?80 and 89% reduction
      in larval damage. The 40 and 500 densities are recommended to Chinese rice
      farmers for mass trapping and mating disruption programs, respectively.

PMID- 26309274
TI  - Spatial Distribution of Brown Marmorated Stink Bug (Hemiptera: Pentatomidae)
      Injury at Harvest in Mid-Atlantic Apple Orchards.
AB  - Brown marmorated stink bug, Halyomorpha halys (Stal), injury to late-season apple
      cultivars was measured at harvest in 2011 and 2012 in commercial orchards in four
      mid-Atlantic states. In each orchard block, a border zone (adjacent to woods), an
      interior zone (near orchard center), and an intermediate zone (between border and
      interior zones) comprised 1-3 tree rows per zone, depending on block size. Just
      before commercial harvest, 10 fruit were sampled from the upper, middle, and
      lower third of the canopy from five trees in each zone. After 3-5 wk in cold
      storage, fruit were examined for external and internal injury, and severity of
      internal injury (number of injury sites per fruit) from H. halys. A zero-inflated
      negative binomial model accounted for significant variation among the orchards
      and showed that apples from the upper canopy of border zone trees had the highest
      probability of experiencing external and internal injury. A minor interaction was
      detected among the orchards and zones for injury prevalence and severity, but
      there was no evidence of an orchard showing less expected injury in the border
      zone compared with other zones. Adjusting for orchard-to-orchard variation,
      differences in injury distributions among the zones and canopies were primarily
      due to injury prevalence rather than expected injury severity. The implications
      of these results to scouting and managing H. halys in eastern apple orchards are
      discussed.

PMID- 26309275
TI  - Use of Early Ripening Cultivars to Avoid Infestation and Mass Trapping to Manage
      Drosophila suzukii (Diptera: Drosophilidae) in Vaccinium corymbosum (Ericales:
      Ericaceae).
AB  - Use of early ripening highbush blueberry cultivars to avoid infestation and mass
      trapping were evaluated for managing spotted wing drosophila, Drosophila suzukii
      (Matsumura). Fourteen highbush blueberry cultivars were sampled for spotted wing
      drosophila infestation. Most 'Earliblue', 'Bluetta', and 'Collins' fruit were
      harvested before spotted wing drosophila oviposition commenced, and so escaped
      injury. Most fruit from 'Bluejay', 'Blueray', and 'Bluehaven' were also harvested
      before the first week of August, after which spotted wing drosophila activity led
      to high levels of blueberry infestation. In a separate experiment, damage to
      cultivars was related to the week in which fruit were harvested, with greater
      damage to fruit observed as the season progressed. Attractant traps placed within
      blueberry bushes increased nearby berry infestation by 5%, irrespective of
      cultivar and harvest date. The significant linear reduction in infestation with
      increasing distance from the attractant trap suggests that traps are influencing
      fly behavior to at least 5.5 m. Insecticides applied to the exterior of traps,
      compared with untreated traps, revealed that only 10-30% of flies visiting traps
      enter the traps and drown. Low trap efficiency may jeopardize surrounding fruits
      by increasing local spotted wing drosophila activity. To protect crops, traps for
      mass trapping should be placed in a perimeter outside fruit fields and
      insecticides need to be applied to the surface of traps or on nearby fruit to
      function as an attract-and-kill strategy.

PMID- 26309276
TI  - The Effects of Kernel Feeding by Halyomorpha halys (Hemiptera: Pentatomidae) on
      Commercial Hazelnuts.
AB  - Halyomorpha halys Stal, the brown marmorated stink bug (Hemiptera: Pentatomidae),
      is an invasive pest with established populations in Oregon. The generalist
      feeding habits of H. halys suggest it has the potential to be a pest of many
      specialty crops grown in Oregon, including hazelnuts, Corylus avellana L. The
      objectives of this study were to: 1) characterize the damage to developing
      hazelnut kernels resulting from feeding by H. halys adults, 2) determine how the
      timing of feeding during kernel development influences damage to kernels, and 3)
      determine if hazelnut shell thickness has an effect on feeding frequency on
      kernels. Adult brown marmorated stink bugs were allowed to feed on developing
      nuts for 1-wk periods from initial kernel development (spring) until harvest
      (fall). Developing nuts not exposed to feeding by H. halys served as a control
      treatment. The degree of damage and diagnostic symptoms corresponded with the
      hazelnut kernels' physiological development. Our results demonstrated that when
      H. halys fed on hazelnuts before kernel expansion, development of the kernels
      could cease, resulting in empty shells. When stink bugs fed during kernel
      expansion, kernels appeared malformed. When stink bugs fed on mature nuts the
      kernels exhibited corky, necrotic areas. Although significant differences in
      shell thickness were observed among the cultivars, no significant differences
      occurred in the proportions of damaged kernels based on field tests and
      laboratory choice tests. The results of these studies demonstrated that
      commercial hazelnuts are susceptible to damage caused by the feeding of H. halys
      throughout the entire period of kernel development.

PMID- 26309277
TI  - Cost-Benefit Analysis of Managing the Papuana uninodis (Coleoptera: Scarabaeidae)
      Taro Beetle in Fiji.
AB  - Taro (Colocasia esculenta (L.) Schott) plays a prominent role in the economies
      and cultures of Pacific Island countries such as Fiji. Unfortunately, taro is
      highly susceptible to invasion from taro beetles, which burrow into the corms and
      weaken the plants, rendering them unmarkable and prone to rot. Papuana uninodis
      Prell, an invasive alien species that is native to the Solomon Islands and
      Vanuatu, was first reported on Viti Levu (Fiji's largest island) in 1984. Since
      that time, taro production on Viti Levu has fallen substantially. In this paper,
      we employ data from surveys of households and communities to document the impacts
      of P. uninodis on Viti Levu. We then identify three management approaches
      chemical controls, cultural controls, and switching from taro to another staple
      crop-and conduct a cost-benefit analysis of each. We find strong arguments for
      pursuing chemical control, which derives a net present value of monetised
      benefits of about FJ&dollar;139,500 per hectare over 50 yr, or >FJ&dollar;21 for
      each FJ&dollar;1 spent. Still, any of the three management options is more
      efficient than no management, even without any attempt to quantify the benefits
      to biodiversity or forest protection, underscoring the value of actively managing
      this invasive alien species.

PMID- 26309278
TI  - Behavioral Effects and Tunneling Responses of Eastern Subterranean Termites
      (Isoptera: Rhinotermitidae) Exposed to Chlorantraniliprole-Treated Soils.
AB  - Intrinsic toxicities of chlorantraniliprole, fipronil, and imidacloprid were
      evaluated with topical applications on worker termites. Worker termites were
      exposed to substrates treated with formulated chlorantraniliprole to study
      contact toxicity, tunneling, and postexposure behaviors. The intrinsic toxicities
      (LD50, ng/termite) of chlorantraniliprole (1.25, 0.96, and 0.44) and fipronil
      (0.12, 0.11, and 0.13) at 11 d were similar for workers from three termite
      colonies. Imidacloprid toxicity (LD50) values were highly variable among the
      workers from three different colonies, values at 11 d ranging from 0.7 to 75
      ng/termite. Termite workers exposed to sand and soils treated with
      chlorantraniliprole at 50 ppm exhibited delayed mortality and, for most of the
      exposure times, it took >5 d to observe 90-100% mortality in termite workers.
      Exposure to chlorantraniliprole-treated sand (50 ppm) for as little as 1 min
      stopped feeding and killed 90-100% of the workers. Tunneling (~ 2 h) in different
      soil types treated with chlorantraniliprole at 50 ppm, even those with high
      organic matter (6.3%) and clay content (30%), caused immediate feeding cessation
      in worker termites and mortality in the next 7-14 d. Worker termites exposed for
      1 and 60 min to sand treated with chlorantraniliprole (50 ppm) were able to walk
      normally for 4 h after exposure in most cases. Delayed toxicity, increased
      aggregation, and grooming were observed in exposed termites and discussed in the
      context of horizontal transfer effects within termite colonies.

PMID- 26309279
TI  - Field and Laboratory Evaluations of Chlorantraniliprole as a Termiticide in
      Southern Arizona.
AB  - The desert subterranean termite, Heterotermes aureus (Snyder), is the predominant
      termite of economic importance in the arid southwest. Chlorantraniliprole, a
      relatively new nonrepellent, slow acting termiticide has been shown to be capable
      of being transferred among colony members through social interactions, and thus
      may be effective beyond its original site of application. Using field grids, we
      evaluated the colony-level effects of chlorantraniliprole on H. aureus foraging
      activity. Repeated laboratory soil bioassays at 3, 15, 27 and 39 mo
      postapplication were performed to determine the effects of chlorantraniliprole on
      termite mortality and tunneling activity. Additionally, field tests of
      chlorantraniliprole were completed on 10 structures infested with H. aureus. In
      the experimental grids, the zone surrounded by a chlorantraniliprole perimeter
      was the only section in which a significant decrease in the number of termites
      collected occurred, but this was observed in both treatment and controls plots.
      Overall, no significant colony-level effects of chlorantraniliprole application
      were observed within the grids. Laboratory bioassays resulted in high mortality
      and significantly lower tunneling activity of exposed termites at all time
      points. In structures, the initial application of chlorantraniliprole was
      sufficient to control infestations in 6 out of 10 cases without supplemental
      applications. Additional treatments were confined to areas that had not been
      treated previously. Results show that chlorantraniliprole is capable of achieving
      control of desert subterranean termites under most conditions. This is likely a
      result of its high toxicity instead of colony-level effects resulting from
      termiticide transfer.

PMID- 26309280
TI  - Stage-Specific Expression of Resistance to Different Acaricides in Four Field
      Populations of Tetranychus urticae (Acari: Tetranychidae).
AB  - The two-spotted spider mite, Tetranychus urticae Koch, is a worldwide crop pest.
      The resistance to commonly applied acaricides (in this report, "acaricide" refers
      to both acaricides and insecticides that are toxic to mites) has seriously
      impaired T. urticae control in the field. Here, the sensitivity of eggs, larvae,
      and adults of laboratory and field populations of T. urticae to various
      acaricides was investigated. Based on data obtained with an acaricide-sensitive
      laboratory strain collected in 2009, abamectin was the most toxic of the tested
      acaricides. For each acaricide, susceptibility was greatest for larvae, least for
      adults, and intermediate for eggs. The egg was the most sensitive stage to
      abamectin, bifenazate, and hexythiazox; the larva was the most sensitive stage to
      abamectin, hexythiazox, bifenazate, propargite, and chlorfenapyr; and the adult
      was the most sensitive stage to abamectin, bifenazate, and chlorfenapyr. Based on
      the results obtained with the acaricide-sensitive laboratory strain, acaricides
      were selected to test against eggs, larvae, and adults of four field populations
      of T. urticae from Beijing, China. Although the field populations differed in
      their resistance to the acaricides in laboratory bioassays, the eggs, larvae, and
      adults of the four populations were sensitive to bifenazate and highly resistant
      to abamectin. Field trials for control of T. urticae in Beijing, China, should be
      conducted with bifenazate and other acaricides rather than with abamectin.

PMID- 26309281
TI  - Incidence and Characterization of Resistance to Fenpropathrin in Some Liriomyza
      sativae (Diptera: Agromyzidae) Populations in Iran.
AB  - The vegetable leafminer, Liriomyza sativae Blanchard, is a key pest of vegetable
      and ornamental crops worldwide and is mainly controlled by insecticides. The
      toxicity of fenpropathrin on adult flies of F1 generation of six Iranian
      populations of the pest was assessed using the residual glass vial method. The
      bioassay results showed significant differences in susceptibility to
      fenpropathrin among the populations tested. Resistance ratios ranged from 5.09 to
      28.32. The resistant populations were reared in the greenhouse under
      fenpropathrin pressure for 14 mo and then susceptibility of both larvae and
      adults of these strains to fenpropathrin was evaluated. The resistance levels
      significantly increased in these populations. Further study demonstrated that
      diethyl maleate and triphenyl phosphate had no synergistic effects on
      fenpropathrin, however, this compound was significantly synergized by piperonyl
      butoxide in all tested populations. S,S,S-tributyl phosphorotrithioate also
      showed a slight synergism with fenpropathrin. Enzyme assays for general
      esterases, glutathione S-transferases and monooxygenases were performed on adults
      and larvae of L. sativae. The activity of glutathione s-transferase in different
      resistant and susceptible strains was not significantly different. The activity
      of esterases in resistant strains was higher than the susceptible strain.
      Monooxygenase levels also were higher in resistant strains compared with the
      susceptible strain. Synergism and biochemical assays revealed that esterases and
      monooxygenases have a major role in resistance of L. sativae to fenpropathrin.

PMID- 26309282
TI  - Susceptibility of Sogatella furcifera and Laodelphax striatellus (Hemiptera:
      Delphacidae) to Six Insecticides in China.
AB  - The whitebacked planthopper, Sogatella furcifera (Horvath), and small brown
      planthopper, Laodelphax striatellus (Fallen), both are important crop pests
      throughout China, especially in rice. Application of chemical insecticides is the
      major control practice. Consequently, insecticide resistance has become an urgent
      issue. In this study, resistance levels to six conventional insecticides were
      evaluated for these two species collected from major occurring areas of China.
      Additionally, imidacloprid- (resistance ratio [RR] = 10.4-fold) and buprofezin
      (RR = 15.1-fold)-resistant strains of whitebacked planthopper were obtained
      through laboratory selections for cross-resistance profiling and synergism
      assessment to understand resistance mechanisms. The results showed that all
      tested populations of both species exhibited low to high levels of resistance to
      chlorpyrifos, while remaining susceptible to thiamethoxam. Three of the 14
      whitebacked planthopper populations showed low to moderate resistance to
      imidacloprid, while all small brown planthopper populations reminded susceptible.
      All small brown planthopper and whitebacked planthopper (except one) populations
      showed at least moderate resistance (RR = 10.1-271.1) to buprofezin. All small
      brown planthopper populations remained susceptible to pymetrozine and nitenpyram,
      and all whitebacked planthopper populations remained susceptible to isoprocarb.
      The imidacloprid-resistant whitebacked planthopper strain showed no significant
      cross-resistance to other tested insecticides. However, the buprofezin-resistant
      strain exhibited a low-level cross-resistance (CR = 3.1) to imidacloprid.
      Piperonyl butoxide, triphenyl phosphate, and diethylmaleate displayed no
      synergism effect on the resistant whitebacked planthopper strains.

PMID- 26309283
TI  - Toxicity and Cross-Resistance of Insecticides to Cry2Ab-Resistant and Cry2Ab
      Susceptible Helicoverpa armigera and Helicoverpa punctigera (Lepidoptera:
      Noctuidae).
AB  - Since 2004-2005 cotton expressing Cry1Ac and Cry2Ab insecticidal proteins from
      the bacterium Bacillus thuringiensis has been commercially available in Australia
      to manage the target pests Helicoverpa armigera (Hubner) and Helicoverpa
      punctigera (Wallengren). In both target species, the frequency of alleles
      conferring resistance to Cry2Ab is unexpectedly high in field populations. A
      significant challenge for managing these pests would occur if resistance to
      Cry2Ab toxins inadvertently selected for resistance to other insecticides used to
      control them. Dose-response bioassays were performed to measure the toxicity of
      currently registered insecticide sprays on isogenic strains of Cry2Ab-resistant
      and Cry2Ab-susceptible H. armigera and H. punctigera. Within-species comparisons
      of Cry2Ab-resistant and Cry2Ab-susceptible strains of H. armigera and H.
      punctigera indicate no cross-resistance with pyrethroid insecticides.
      Additionally, Cry2Ab-resistant strains were not cross-resistant to the following
      selective insecticides: indoxacarb, chlorantraniliprole, and avermectins. In both
      H. armigera and H. punctigera, Cry2Ab-resistant colonies exhibited a small, but
      significant, degree of enhanced susceptibility in response to chlorpyrifos and
      methomyl. We report higher tolerance to conventional insecticides in H. armigera
      compared with H. punctigera. Our results indicate that there is no significant
      interplay between Cry2Ab resistance frequencies in H. armigera and H. punctigera
      and frequencies of resistance to a range of insecticide sprays currently
      registered for cotton. Therefore, we conclude that any increases in frequencies
      of the common Cry2Ab resistance phenotypes identified in Australian populations
      of Helicoverpa spp. are unlikely to increase resistance risk for the indoxacarb,
      chlorantraniliprole, or avermectin classes of insecticide.

PMID- 26309285
TI  - Genetic Diversity of Bactrocera dorsalis (Diptera: Tephritidae) on the Hawaiian
      Islands: Implications for an Introduction Pathway Into California.
AB  - Population genetic diversity of the oriental fruit fly, Bactrocera dorsalis
      (Hendel), on the Hawaiian islands of Oahu, Maui, Kauai, and Hawaii (the Big
      Island) was estimated using DNA sequences of the mitochondrial cytochrome c
      oxidase subunit I gene. In total, 932 flies representing 36 sampled sites across
      the four islands were sequenced for a 1,500-bp fragment of the gene named the
      C1500 marker. Genetic variation was low on the Hawaiian Islands with >96% of
      flies having just two haplotypes: C1500-Haplotype 1 (63.2%) or C1500-Haplotype 2
      (33.3%). The other 33 flies (3.5%) had haplotypes similar to the two dominant
      haplotypes. No population structure was detected among the islands or within
      islands. The two haplotypes were present at similar frequencies at each sample
      site, suggesting that flies on the various islands can be considered one
      population. Comparison of the Hawaiian data set to DNA sequences of 165 flies
      from outbreaks in California between 2006 and 2012 indicates that a single-source
      introduction pathway of Hawaiian origin cannot explain many of the flies in
      California. Hawaii, however, could not be excluded as a maternal source for 69
      flies. There was no clear geographic association for Hawaiian or non-Hawaiian
      haplotypes in the Bay Area or Los Angeles Basin over time. This suggests that
      California experienced multiple, independent introductions from different
      sources.

PMID- 26309284
TI  - Noctilisin, a Venom Glycopeptide of Sirex noctilio (Hymenoptera: Siricidae),
      Causes Needle Wilt and Defense Gene Responses in Pines.
AB  - During oviposition, female Sirex noctilio (F.) (Siricidae) woodwasps inject their
      conifer hosts with a venom gland secretion. The secretion induces a variety of
      host physiological changes that facilitate subsequent lethal infection by a
      symbiotic fungus. A heat-stable factor that can migrate from the site of
      oviposition in the trunk through the xylem to needles in the crown of attacked
      pines was purified by size-fractionation and reversed-phase-high-performance
      liquid chromatography using activity assays based on defense gene induction as
      well as the needle wilt response in pine shoot explants. An 11-amino acid,
      posttranslationally modified peptide (SEGPROGTKRP) encoded by the most abundant
      transcript recovered from S. noctilio venom gland tissue comprised the backbone
      of the 1,850 Da active factor. Posttranslational modifications included
      hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser
      and Thr residues at positions 1 and 8, respectively. The O-linked sugars were
      identical alpha-linked N-acetylgalactosamine residues modified at the C6 position
      by addition of phosphoethanolamine. In contrast to the native peptide, a
      synthetic version of the hydroxylated peptide backbone lacking the glycosyl side
      chains failed to induce pine defense genes or cause needle wilt in excised
      shoots. This peptide, hereafter called noctilisin, is related to the O
      glycosylated short-chain proline-rich antimicrobial peptides exemplified by
      drosocin. The noctilisin structure contains motifs which may explain how it
      avoids detection by pine defense systems.

PMID- 26309286
TI  - Molecular Survey for the Invasive Leafminer Pest Liriomyza huidobrensis (Diptera:
      Agromyzidae) in California Uncovers Only the Native Pest Liriomyza langei.
AB  - Liriomyza huidobrensis (Blanchard) is a highly destructive invasive leafminer
      pest currently causing extensive damage to vegetable and horticultural crops
      around the world. Liriomyza langei Frick is a leafminer pest native to California
      that cannot currently be morphologically distinguished from L. huidobrensis. We
      used a DNA-barcoding approach, a published PCR-RFLP method, and a new multiplex
      PCR method to analyze 664 flies matching the morphological description of
      huidobrensis-langei. We found no evidence for the presence of L. huidobrensis in
      our extensive samples from California. In addition to the new molecular method,
      this work is important because it provides definitive data that the California
      "pea leafminer" is currently, and has probably always been, L. langei. These data
      will also be important in the event that the highly invasive L. huidobrensis ever
      becomes established.

PMID- 26309287
TI  - Detection of the Acetylcholinesterase Insecticide Resistance Mutation (G328A) in
      Natural Populations of Ceratitis capitata.
AB  - Wild Mediterranean fruit fly specimens collected from various regions worldwide
      were screened for the glycine to alanine (Gly->Ala) point mutation (G328A) in the
      acetylcholinesterase enzyme, presumably causing resistance to organophosphates.
      We found that the single nucleotide polymorphism (SNP) responsible for this amino
      acid change is located at the beginning of exon 6 of the Ccace2 gene. The
      identification of the exact location of the SNP permitted PCR primer design
      around this site and direct sequencing of the corresponding genomic region. We
      detected the resistance allele in natural Mediterranean fruit fly populations
      from Brazil and Spain, but not from other sites in four continents. The known
      treatment history of sites suggests that the resistance buildup is linked to
      organophosphate application in the field. The PCR-based detection provides a
      screening method useful for monitoring Mediterranean fruit fly insecticide
      resistance in local populations and improving pest management strategies
      accordingly.

PMID- 26309288
TI  - Effects of Planting Date and Barley Variety on Russian Wheat Aphid (Hemiptera:
      Aphididae) Populations in Colorado, Kansas, and Nebraska.
AB  - The Russian wheat aphid, Diuraphis noxia (Kurdjumov) (Hemiptera: Aphididae), is
      an important pest in the western Great Plains of the United States, where it
      causes hundreds of millions of dollars of losses to barley and wheat production
      through reduced yields. Experiments to evaluate the effect of early planting and
      resistance in barley (Hordeum vulgare L.) on D. noxia were conducted at Fort
      Collins, CO; Tribune, KS; and Sidney, NE, in 2007, 2008, and 2009. Treatments
      included two planting dates and four cultivars, the D. noxia-resistant barley
      cultivars 'Stoneham' (Otis*4/STARS 9577B) and 'Sidney' (Otis*4/STARS 9301B), the
      susceptible cultivar 'Otis', and Otis treated with thiamethoxam. In tiller
      samples collected from May through early July, consistently lower D. noxia
      populations were found in plots planted ?30 d earlier than normal at Fort Collins
      in all three years, and at Tribune in 2007. With one location-year exception,
      lower D. noxia populations occurred on plants of resistant varieties or the
      susceptible variety Otis treated with thiamethoxam than on untreated Otis plants.
      There were no significant differences in D. noxia populations produced on plants
      of either resistant variety and susceptible Otis plants treated with
      thiamethoxam. Interactions between resistant varieties and early planting
      resulted in reduced D. noxia populations at Fort Collins in 2007 and 2009, and at
      Tribune and Sidney in 2007. Planting D. noxia-resistant barley varieties,
      planting varieties earlier than normal, and the synergistic effect of resistant
      variety and early planting can significantly reduce D. noxia infestations on
      barley in the western High Plains.

PMID- 26309289
TI  - Candidate Genes Expressed in Tolerant Common Wheat With Resistant to English
      Grain Aphid.
AB  - The English grain aphid, Sitobion avenae (F.) (Hemiptera: Aphididae), is a common
      worldwide pest of wheat (Triticum aestivum L.). The use of improved resistant
      cultivars by the farmers is the most effective and environmentally friendly
      method to control this aphid in the field. The winter wheat genotypes 98-10-35
      and Amigo are resistant to S. avenae. To identify genes responsible for
      resistance to S. avenae in these genotypes, differential-display reverse
      transcription-polymerase chain reaction was used to identify the corresponding
      differentially expressed sequences in current study. Two backcross progenies were
      obtained by crossing the two resistant genotypes with the susceptible genotype
      1376. Six potential expected-differential bands were sequenced. Lengths of the
      expressed sequence tags ranged from 128 to 532 bp. Although these expressed
      sequences were likely associated with S. avenae resistance, there was one
      expressed sequence tag located on 7DL chromosome, and its potential function may
      associate with the ability to maintain photosynthesis in wheat. That serves as an
      active way for tolerant common wheat with resistant to S. avenae. Cloning the
      full length of these sequences would help us thoroughly understand the mechanism
      of wheat resistance to S. avenae and be valuable for breeding cultivars with S.
      avenae resistance.

PMID- 26309290
TI  - Characterization of Peroxidase Changes in Tolerant and Susceptible Soybeans
      Challenged by Soybean Aphid (Hemiptera: Aphididae).
AB  - Changes in protein content, peroxidase activity, and isozyme profiles in response
      to soybean aphid feeding were documented at V1 (fully developed leaves at
      unifoliate node, first trifoliate leaf unrolled) and V3 (fully developed leaf at
      second trifoliate node, third trifoliate leaf unrolled) stages of soybean aphid
      tolerant (KS4202) and -susceptible (SD76R) soybeans. Protein content was similar
      between infested and control V1 and V3 stage plants for both KS4202 and SD76R at
      6, 16, and 22 d after aphid introduction. Enzyme kinetics studies documented that
      control and aphid-infested KS4202 V1 stage and SD76R V1 and V3 stages had similar
      levels of peroxidase activity at the three time points evaluated. In contrast,
      KS4202 aphid-infested plants at the V3 stage had significantly higher peroxidase
      activity levels than control plants at 6 and 22 d after aphid introduction. The
      differences in peroxidase activity observed between infested and control V3 stage
      KS4202 plants at these two time points suggest that peroxidases may be playing
      multiple roles in the tolerant plant. Native gels stained for peroxidase were
      able to detect differences in the isozyme profiles of aphid-infested and control
      plants for both KS4202 and SD76R.

PMID- 26309291
TI  - Resistance of Faba Bean and Pea Germplasm to Callosobruchus chinensis
      (Coleoptera: Bruchidae) and Its Relationship With Quality Components.
AB  - In total, 339 faba bean (Vicia faba L.) and 100 pea (Pisum sativum L.) accessions
      were screened for their ability to resist Callosobruchus chinensis L. in free
      choice laboratory tests. Four, 15, and 43 faba bean varieties were highly
      resistant, resistant, and moderately resistant to C. chinensis, respectively.
      Three immune, three highly resistant, and six resistant accessions were
      discovered among the pea germplasm. The faba bean and pea varieties presented a
      hundred-kernel weight reduction varied from 0.18 to 35.36% for faba bean
      varieties and 0 to 56.53% for pea varieties. Varieties with brown and black seed
      color had significantly fewer wormholes and higher C. chinensis resistance than
      varieties with light-color seeds. Resistance to C. chinensis showed a
      significant, positive correlation with catechin, total polyphenol, and gamma
      aminobutyric acid contents, but a significant, negative correlation with
      oligosaccharide content. Correlation coefficients (r) between infestation rate of
      faba bean and total phenol, catechin, and oligosaccharide contents were -0.9723, 
      0.8071, and 0.7631, respectively. The values of r for pea resistance and total
      phenol, catechin, and oligosaccharide content were -0.8846, -0.7666, and 0.8308,
      respectively. The results suggest that quality components in faba bean and pea
      have a great role in resistance against C. chinensis.

PMID- 26309293
TI  - Host Plant Probing Analysis Reveals Quick Settlement of the Solenopsis Mealybug
      During Host Shift.

PMID- 26309292
TI  - Exogenous Salicylic Acid Enhances the Resistance of Wheat Seedlings to Hessian
      Fly (Diptera: Cecidomyiidae) Infestation Under Heat Stress.
AB  - Heat stress exerts significant impact on plant-parasite interactions.
      Phytohormones, such as salicylic acid (SA), play important roles in plant defense
      against parasite attacks. Here, we studied the impact of a combination of heat
      stress and exogenous SA on the resistance of wheat (Triticum aestivum L.) plants
      to the Hessian fly [Mayetiola destructor (Say)]. We found that the wheat cultivar
      'Molly', which contains the resistance gene H13, lost resistance to Hessian fly
      under heat stress (40 degrees C for 3 and 6 h), and that exogenous application of
      SA on Molly seedlings right before heat stress can partially prevent the loss of
      resistance of Molly plants under heat conditions. Our findings have significant
      implications for understanding the dynamics of plant-insect interactions in the
      context of heat stress.

PMID- 26309294
TI  - Ross River Virus Disease Activity Associated With Naturally Occurring Nontidal
      Flood Events in Australia: A Systematic Review.
AB  - Ross River virus (RRV) disease is the most common and widespread mosquito-borne
      disease in Australia, resulting in considerable health and economic cost to
      communities. While naturally occurring nontidal flood events may enhance mosquito
      abundance, little is known about the impact of such events on RRV transmission.
      This article critically reviews the existing evidence for an association between
      naturally occurring nontidal flood events and RRV transmission. A systematic
      literature search was conducted on RRV transmission related to flooding and
      inundation from rain and riverine overflow. Overall, the evidence to support a
      positive association between flooding and RRV outbreaks is largely
      circumstantial, with the literature mostly reporting only coincidental occurrence
      between the two. However, for the Murray River, river flow and height (surrogates
      of flooding) were positively and significantly associated with RRV transmission.
      The association between nontidal flooding and RRV transmission has not been
      studied comprehensively. More frequent flood events arising from climate change
      may result in increased outbreaks of RRV disease. Understanding the link between
      flood events and RRV transmission is necessary if resources for mosquito spraying
      and public health warnings are to be used more effectively and efficiently. 

PMID- 26309295
TI  - Simulium (Simulium) lomkaoense, a New Species of Black Fly (Diptera: Simuliidae)
      From Thailand.
AB  - Simulium (Simulium) lomkaoense sp. nov. is described from females, males, pupae,
      and larvae in Thailand. This new species is assigned to the Simulium malyschevi
      Dorogostaisky, Rubtsov & Vlasenko species-group of the subgenus Simulium, and
      appears to be closely related to Simulium baimaii Kuvangkadilok & Takaoka from
      Thailand in having a similar shape of the female and male genitalia, pupal gill
      with two inflated filaments, and simple wall-pocket-shaped cocoon. This new
      species is compared taxonomically with S. baimaii and other related species. It
      represents the third species of the S. malyschevi species-group known from
      Thailand. 

PMID- 26309296
TI  - Key to Species of the Genus Neocheyletiella (Acariformes: Cheyletidae), With
      Description of a New Species.
AB  - A new species of the genus Neocheyletiella Baker, 1949 (Acariformes: Cheyletidae)
      is described from the zebra finch, Taeniopygia guttata (Viellot, 1817)
      (Passeriformes: Estrildidae), from a laboratory colony at the Massachusetts
      Institute of Technology, Cambridge, MA. The setal additions in the ontogeny of
      the new species, Neocheyletiella parvisetosa Mertins & Bochkov, and the main
      differential characters of all 17 known species of the genus Neocheyletiella are
      provided in tabular format. Keys to females and males of Neocheyletiella spp.
      also are given. 

PMID- 26309297
TI  - Novel Primers From Informative Nuclear Loci for Louse Molecular Phylogenetics
      (Insecta: Phthiraptera).
AB  - While parasitic lice (Insecta: Phthiraptera) have historically been an important
      model taxon for understanding host-parasite coevolution, very few molecular
      markers have been developed for phylogenetic analysis. The current markers are
      insufficient to resolve many of the deeper nodes in this group; therefore,
      sequences from additional genetic loci are necessary. Here, we design primers
      targeting several nuclear protein coding genes based on a complete genome and
      transcriptome of Pediculus humanus L. plus transcriptomes and modest coverage
      genomic data from five genera of avian feather lice. These primers were tested on
      32 genera of avian feather lice (Ischnocera), including multiple species within
      some genera. All of the new primer combinations produced sequences for the
      majority of the genera and had similar or higher divergences than the most widely
      used nuclear protein-coding gene in lice, EF-1alpha. These results indicate that
      these new loci will be useful in resolving phylogenetic relationships among
      parasitic lice. 

PMID- 26309298
TI  - Species Diversity, Seasonal, and Spatial Distribution of Mosquitoes (Diptera:
      Culicidae) Captured in Aotus Monkey-Baited Traps in a Forested Site Near Iquitos,
      Peru.
AB  - This study was conducted to determine the relative abundance, diversity,
      seasonal, and vertical distributions of potential mosquito vectors in the Amazon
      Basin, Peru. A total of 66,097 mosquitoes (50 mosquito species from 12 genera)
      were collected from May 2001 through March 2002 at a forested site near Iquitos,
      Peru. Mosquitoes were collected using Aotus nancymae Hershkovitz monkey-baited
      CDC light traps set for 12-h day and night periods at varying heights (e.g.,
      ground and canopy) in the forest. Of the 12 genera, three accounted for 75% of
      all mosquitoes collected: Culex (33%), Aedes (23%), and Psorophora (18%). The
      most prevalent species collected were Aedes serratus (Theobald), Culex pedroi
      Sirivanakarn & Belkin, Psorophora albigenu (Peryassu), and a combination of
      Mansonia indubitans Dyar & Shannon and Mansonia titillans (Walker), which
      accounted for 56% of all mosquitoes captured. In general, mosquitoes were
      collected more often at night and on the ground. Exceptions include
      Coquillettidia venezuelensis (Theobald), which were collected in relatively even
      numbers at both day and night and most Mansonia and some species of Anopheles,
      which were collected more often in the canopy. Total mosquito populations had two
      peaks, June-July (Ma. indubitans/titillans and Cq. venezuelensis) and December
      January (Ps. albigenu, Cx. pedroi, and Ae. serratus). Observations of the eight
      most collected mosquitoes indicated that behavioral shifts were not observed
      between collection months. These data provide a better understanding of the
      species diversity, population density, and seasonal distribution of potential
      mosquito vectors within the Amazon Basin region and allow for the development of
      appropriate vector and disease prevention strategies. 

PMID- 26309299
TI  - Spiders (Araneae) Found in Bananas and Other International Cargo Submitted to
      North American Arachnologists for Identification.
AB  - Spiders found in international cargo brought into North America are sometimes
      submitted to arachnologists for identification. Often, these spiders are presumed
      to be of medical importance because of size or a submitter's familiarity with a
      toxic spider genus from the continent of origin. Starting in 2006, requests were
      made for spiders found in international cargo brought into North America, in
      addition to the specimens from similar cargo shipments already in our museum
      collections. This was an ad hoc study that allowed us to focus on spiders of
      concern to the discoverer. We identified 135 spiders found in international
      cargo. A key for the most common species is provided. The most frequently
      submitted spiders were the pantropical huntsman spider, Heteropoda venatoria (L.)
      (Sparassidae), and the redfaced banana spider, Cupiennius chiapanensis Medina
      Soriano (Ctenidae). Spiders of medical importance were rare. The most common
      cargo from which spiders were submitted was bananas with most specimens coming
      from Central America, Ecuador, or Colombia. Lack of experience with nonnative
      fauna caused several experienced American arachnologists to misidentify harmless
      ctenid spiders (C. chiapanensis, spotlegged banana spider, Cupiennius getazi
      Simon) as highly toxic Phoneutria spiders. These misidentifications could have
      led to costly, unwarranted prophylactic eradication measures, unnecessary
      employee health education, heightened employee anxiety and spoilage when
      perishable goods are left unloaded due to safety concerns. 

PMID- 26309300
TI  - Development and Oviposition Preference of House Flies and Stable Flies (Diptera:
      Muscidae) in Six Substrates From Florida Equine Facilities.
AB  - House flies, Musca domestica L., and stable flies, Stomoxys calcitrans (L.),
      (Diptera: Muscidae), common pests on equine facilities, were studied in the
      laboratory to determine the success and duration of larval development and
      oviposition preferences on six substrates commonly found on equine facilities.
      Substrates tested were hay soiled with urine and manure, fresh horse manure, pine
      shaving bedding soiled with urine and manure (<12 h old), pine shaving bedding
      soiled with urine and manure (aged >72 h in a manure pile), builders sand bedding
      soiled with urine and manure aged 3 d, and soil from an overgrazed pasture mixed
      with urine and manure of variable age. House fly larvae failed to develop into
      adults in hay, soil, and sand substrates. Stable flies preferred to oviposit on
      substrates with plant material and not on fresh manure. However, when eggs were
      added to the substrates, pupariation was maximal in fresh manure and the fresh
      pine shaving substrate. Stable flies developed in all six equine substrates, but
      development was less successful on the substrates with soil. In choice tests,
      fresh manure and the fresh pine shaving substrates were the most attractive for
      house fly oviposition. These substrates also yielded the greatest number of house
      fly puparia from artificially added eggs. An understanding of oviposition
      preferences and differential larval development of house flies and stable flies
      on these substrates may help develop options for reducing pest populations by
      effectively managing equine waste and selecting appropriate bedding materials. 

PMID- 26309302
TI  - Effects of Competition and Predation by Native Mosquitoes on the North American
      Invasion of Aedes japonicus japonicus (Diptera: Culicidae).
AB  - The success and effects of a biological invasion can be dependent on species
      interactions with resident competitors and predators. Indirect interactions
      between competition and predation, such as keystone predation, can influence both
      invasion success and the impact of an invasive species on resident competitors.
      The invasive mosquito Aedes japonicus japonicus (Theobald) has been established
      within the North American range of the indigenous competitor Aedes triseriatus
      (Say) and indigenous mosquito predator Toxorhynchites rutilus (Coquillett). The
      effects of Tx. rutilus predation on competition between Ae. j. japonicus and Ae.
      triseriatus were tested in laboratory microcosms. Consistent with a prior study,
      there was minimal evidence of competitive asymmetry between Ae. j. japonicus and
      Ae. triseriatus, with similar effects of intraspecific versus interspecific
      interactions on both species. Tx. rutilus predation caused high mortality of both
      Ae. j. japonicus and Ae. triseriatus, and minimized the effects of density
      dependent competition. Ae. japonicus females that survived predation had larger
      adult body sizes than those in treatments without predators. Ae. triseriatus
      females that survived Tx. rutilus predation were larger and developed quicker
      than individuals in treatments without predators. Intraspecific competition and
      predation negatively affected the finite rate of population increase for Ae. j.
      japonicus, but only affected individual fitness correlates for Ae. triseriatus,
      indicating that the overall population performance of the invader is more
      sensitive to these interactions than the native species. Based on these results,
      we predict that predation is likely to be an important barrier to the
      establishment and spread of Ae. j. japonicus in tree holes in North America. 

PMID- 26309301
TI  - Desiccation Tolerance in the Eggs of the Primary North American Bluetongue Virus
      Vector, Culicoides sonorensis (Diptera: Ceratopogonidae), and Implications for
      Vector Persistence.
AB  - Culicoides sonorensis Wirth and Jones transmits bluetongue virus and develops in
      a variety of polluted mud habitats. Egg desiccation tolerance was tested by
      obtaining eggs of known age, drying them, and placing them back on wet substrate.
      Eggs 4-10 h old failed to hatch after 12 h of drying at 75% relative humidity
      (RH). Older eggs (28-34 h) survived severe desiccation and >50% water weight
      loss. They regained their water within ~2 h of rehydration. Relative to control
      eggs, average egg hatch was reduced by 36% after 12 h of drying, 79% after 24 h,
      91% after 36 h, and 97% after 48 h. Some embryos (1%) survived and hatched after
      60 h of drying and water losses of nearly 60%. Eggs in specific 25-40 h age
      categories did not differ in hatch after a 12-h desiccation stress; critical
      embryo age to survive drying is between 10 and 24 h. Humidity gradients relieved
      desiccation stress, and eggs appeared to regain water from saturated RH
      conditions. Individual, gravid C. sonorensis oviposited in 1-liter containers
      with an artificial mud bank. If they laid eggs, 73% deposited them singly in
      lines ranging up to 5-6 cm in length (meanderers), while 27% laid eggs in clumps
      (dumpers). Eggs were positioned an average of 45 +/- 12 mm back from waterline.
      Younger eggs, if laid in early evening, may not experience severe desiccation.
      Embryo recovery from such severe desiccation could be adaptive in ephemeral
      habitats where the species may have evolved. 

PMID- 26309303
TI  - Insect Colonization and Succession on Rabbit Carcasses in Southwestern Mountains
      of the Kingdom of Saudi Arabia.
AB  - This study describes for the first time the necrophagous insects attracted to
      carcasses of the European rabbit in the mountains of Al-Baha Province of
      southwestern Kingdom of Saudi Arabia (KSA). Twenty-four rabbit carcasses were
      exposed in 2010 during spring (March, April, and May), summer (June, July, and
      August), and autumn (September, October, and November). The calliphorid fly
      species, Calliphora vicina Robineau-Desvoidy, Chrysomya marginalis (Wiedemann),
      Chrysomya chloropyga (Wiedemann), Chrysomya albiceps (Wiedemann), and Lucilia
      cuprina (Wiedemann), the sarcophagid Liosarcophaga babiyari (Lehrer), and muscoid
      flies Musca domestica (L.) and Musca stabulans Fallen were attracted to the
      carcasses. Seven species of Coleoptera, the dermestid Dermestes maculatus (De
      Geer), three species of hister beetles, Saprinus moyses Marseul, Saprinus ruber
      gemminigeri, and Saprinus chalcites (Illiger), the tenebrionid Himatismus sp.,
      the clerid species, Necrobia ruficollis (F.), and the staphylinid beetle
      Creophilous maxillosus (L.) were also attracted to the rabbit carcasses. One
      species of adult pteromalid fly pupal parasitoid Nasonia sp. was also collected.
      The dominant larvae on all the rabbit carcasses were Ch. albiceps, L. cuprina,
      and Li. babiyari. Insect activity caused rabbit carcasses to decompose faster
      during summer (21.38 +/- 0.49 d) compared with spring (27.5 +/- 0.73 d) and
      autumn (30.38 +/- 0.50 d). This study indicates that in this region of KSA, Ch.
      albiceps, L. cuprina, and Li. babiyari are species useful for estimating minimal
      postmortem intervals. 

PMID- 26309304
TI  - Effects of Larval Density and Habitat Drying on Developmental Success of
      Ochlerotatus albifasciatus (Diptera: Culicidae) in Urban Rain Pools: Evidence
      From Field and Experimental Studies.
AB  - Ochlerotatus albifasciatus (Macquart) (Diptera: Culicidae) larvae develop
      synchronously after rainfall events in ephemeral or temporary pools, where they
      occasionally attain very high abundance. The aims of the current study were to
      analyze the response of life history parameters such as daily larval mortality,
      time to pupation, and adult size of Oc. albifasciatus to increasing larval
      density under controlled conditions, and to analyze the relationships of daily
      larval mortality with density and environmental variables (drying rate,
      temperature, and season) in urban rain pools in Buenos Aires, Argentina. An
      exponential increase in mortality was observed at high larval densities under
      controlled conditions. Development times and adult size (wing length) differed
      between males and females, and were also affected by density. Development times
      extended for 0.36 d for each order of magnitude of increase in larval density,
      and wing length decreased 0.0021 mm per additional larva in 600 cm(2). Larval
      density in the field varied from <1 larva per square meter to nearly 1100 larvae
      per square meter. Daily larval mortality values in the field were variable (0.02
      0.91), positively related to the drying rate, and exhibited seasonal differences.
      No significant relation with larval density or temperature was found in the
      field. It remains to be established whether the density-independent mortality
      observed in this study is a generalized pattern of Oc. albifasciatus populations
      in Buenos Aires Province or a pattern restricted only to urban habitats. 

PMID- 26309305
TI  - Comparative Behavioral Responses of Pyrethroid-Susceptible and -Resistant Aedes
      aegypti (Diptera: Culicidae) Populations to Citronella and Eucalyptus Oils.
AB  - The objective of this study was to compare the behavioral responses (contact
      irritancy and noncontact spatial repellency) between susceptible and resistant
      populations of Aedes aegypti (L.) (=Stegomyia aegypti) to essential oils,
      citronella, and eucalyptus, Eucalyptus globulus, extracts, using an excito
      repellency test system. N, N-diethyl-meta-toluamide (DEET) was used as the
      standard reference repellent. Mosquitoes included two long-standing insecticide
      susceptible colonies (U.S. Department of Agriculture and Bora Bora) and two
      pyrethroid-resistant populations recently obtained from Phetchabun and
      Kanchanaburi provinces in Thailand. Both DEET and citronella produced a much
      stronger excitation ("irritancy") and more rapid flight escape response in both
      pyrethroid-resistant populations compared with the laboratory populations.
      Noncontact repellency was also greater in the two resistant populations.
      Eucalyptus oil was found to be the least effective compound tested. Differences
      in responses between long-established pyrethroid-susceptible colonies and newly
      established and naturally resistant colonies were clearly demonstrated. These
      findings also demonstrate the need for further comparisons using natural
      pyrethroid-susceptible populations for elucidation of factors that might
      contribute to different patterns of escape behavior. 

PMID- 26309306
TI  - Interspecific Transfer of a Wolbachia Infection Into Aedes albopictus (Diptera:
      Culicidae) Yields a Novel Phenotype Capable of Rescuing a Superinfection.
AB  - Wolbachia are maternally transmitted obligate bacteria that occur naturally in
      many arthropods. The phenotype observed in mosquitoes is known as cytoplasmic
      incompatibility (CI), which results in reduced or absent egg hatch in crosses
      between individuals with different infection types. Applied mosquito control
      strategies propose that by releasing individuals infected with a Wolbachia strain
      that differs from that in the natural host population, CI could be used to
      suppress or replace mosquito populations. Here, using tetracycline treatment and
      embryonic microinjection, Aedes albopictus (Skuse) was cleared of its natural
      Wolbachia infection and artificially infected with a Wolbachia strain originating
      from Aedes riversi Bohart & Ingram. Crossing experiments were carried out to
      determine whether CI could be observed between the artificially infected strain
      (UC), naturally infected (wild type), and uninfected strains of Ae. albopictus.
      Crosses between UC males and uninfected females resulted in no egg hatch, a
      classic unidirectional CI pattern. Crosses between the wild-type and UC strain
      also exhibited a unidirectional pattern of CI, demonstrating that the UC strain
      is compatible with both of the Wolbachia types that occur within Ae. albopictus
      and that wild-type Wolbachia infections are unable to fully rescue the UC
      Wolbachia type. Crosses between the UC strain and another artificially infected
      Ae. albopictus strain (ARwP), were bidirectionally incompatible, demonstrating
      that the UC strain is not compatible with all Wolbachia types. The CI patterns
      observed in this study were atypical and the opposite of that typically observed
      with superinfections. 

PMID- 26309307
TI  - SNPs in Entire Mitochondrial Genome Sequences (~15.4 kb) and cox1 Sequences (~486
      bp) Resolve Body and Head Lice From Doubly Infected People From Ethiopia, China,
      Nepal, and Iran But Not France.
AB  - Some people host lice on the clothing as well as the head. Whether body lice and
      head lice are distinct species or merely variants of the same species remains
      contentious. We sought to ascertain the extent to which lice from these different
      habitats might interbreed on doubly infected people by comparing their entire
      mitochondrial genome sequences. Toward this end, we analyzed two sets of
      published genetic data from double-infections of body lice and head lice: 1)
      entire mitochondrial coding regions (~15.4 kb) from body lice and head lice from
      seven doubly infected people from Ethiopia, China, and France; and 2) part of the
      cox1 gene (~486 bp) from body lice and head lice from a further nine doubly
      infected people from China, Nepal, and Iran. These mitochondrial data, from 65
      lice, revealed extraordinary variation in the number of single nucleotide
      polymorphisms between the individual body lice and individual head lice of double
      infections: from 1.096 kb of 15.4 kb (7.6%) to 2 bps of 15.4 kb (0.01%). We
      detected coinfections of lice of Clades A and C on the scalp hair of three of the
      eight people from Nepal: one person of the two people from Kathmandu and two of
      the six people from Pokhara. Lice of Clades A and B coinfected the scalp hair of
      one person from Atherton, Far North Queensland, Australia. These findings argue
      for additional large-scale studies of the body lice and head lice of double
      infected people. 

PMID- 26309308
TI  - The First Molecular Characterization of Anopheles (Nyssorhynchus) aquasalis
      (Diptera: Culicidae) Vitellogenin Expression Products and a Partial cDNA Sequence
      Isolation.
AB  - Anopheles (Nyssorhynchus) aquasalis Curry, 1932, is an anopheline that plays an
      important role in Plasmodium transmission in the New World. Few studies have
      explored the molecular reproductive biology of this vector species. In the
      current study, we isolated and sequenced a partial, 886 bp, cDNA fragment of a
      vitellogenin (Vtg) gene from An. aquasalis. The transcription profile of this Vtg
      gene in adult females was characterized, and it is similar to other members of
      the Culicidae. We also detected a smaller subunit of An. aquasalis Vtg proteins
      in ovary tissue and characterized its translational profile in previtellogenic
      and vitellogenic females. Our results represent the first molecular
      characterization of An. aquasalis vitellogenin expression products. 

PMID- 26309309
TI  - Inheritance of Resistance to Deltamethrin in Aedes aegypti (Diptera: Culicidae)
      From Cuba.
AB  - The development of pyrethroid resistance in Aedes aegypti (L) (Diptera:
      Culicidae) is a serious concern because major A. aegypti control programs are
      predominantly based on pyrethroid use during epidemic disease outbreaks. Research
      about the genetic basis for pyrethroid resistance and how it is transmitted among
      mosquito populations is needed. The objective of this study was to determine how
      deltamethrin resistance is inherited in the Cuban A. aegypti-resistant reference
      strain. Here, a field population of A. aegypti from Santiago de Cuba (SAN-F14),
      subjected to 14 generations of selection for high deltamethrin resistance level
      (91.25*), was used to prepare reciprocal F1 and backcross progeny with the
      insecticide-susceptible Rockefeller strain. Bioassays with larvae were performed
      according to World Health Organization guidelines. The activities of metabolic
      enzymes were assayed through synergist and biochemical tests. The null hypothesis
      of the parallelism test between the two probit regression lines of the reciprocal
      F1 (susceptible females * resistant males and vice versa) was not rejected at the
      5% significance level (P = 0.42), indicating autosomal inheritance. The LC50
      response of both F1 progenies to deltamethrin was elevated but less than the
      highly resistant SAN-F14 strain. DLC values for the F1 progenies were 0.91 and
      0.87, respectively, suggesting that deltamethrin resistance in the SAN-F14 strain
      is inherited as an autosomal incompletely dominant trait, involving at least two
      factors, which implies a faster development of deltamethrin resistance in larvae
      and lost product effectiveness. Metabolic enzymes including esterases and
      cytochrome P-450 monooxygenases but not glutathione-S-transferases were involved
      in deltamethrin resistance in larvae. 

PMID- 26309310
TI  - Protection From Mosquito Biting Provided by Permethrin-Treated Military Fabrics.
AB  - A study to evaluate the protection provided by permethrin-treated fabric
      following cold-water washing against biting by mosquitoes is reported. Australian
      Defense Force (ADF) disruptive pattern combat uniform (DPCU) shirt fabric and
      entire shirts were treated by dipping in a 0.6% emulsion (Perigen Defense,
      containing 500 g/liter permethrin), and commercial factory treatment in the
      United States (Factory A) and Europe (Factory B). Protection was recorded after
      1, 3, 5, 10, 30, and 50 washes. The treated fabric provided 100% protection
      against bites of Anopheles farauti Laveran for at least 50 washes, although only
      4.8-19.0% of this species fed through untreated DPCU. The protection provided by
      each type of permethrin treatment against Aedes aegypti (L.) biting was variable;
      however, there were no significant differences between the percentage of
      mosquitoes biting between 1 and 10 washes. A comparison between the two factory
      treatments for 1-50 washes also showed no statistical difference in Ae. aegypti
      feeding. Chemical analysis of fabric was conducted using gas chromatography and
      showed that the initial dose was 0.125 mg/cm(2) for Perigen-treated fabric, which
      fell to 0.004 mg/cm(2) after 10 washes. By contrast, factory treatments resulted
      in initial dose rates of 0.20 mg/cm(2) for Factory A and 0.19 mg/cm(2) for
      Factory B. After 10 washes, Factory A-treated fabric had 0.09 mg/cm(2) and
      Factory B 0.15 mg/cm(2) of permethrin. Despite the higher concentrations of
      permethrin in the fabric, there was not a commensurate increase in biting
      protection provided by the factory-treated fabric, compared with fabric treated
      by dipping in permethrin emulsion. 

PMID- 26309311
TI  - Influence of Time of Assay on Behavioral Responses of Laboratory and Field
      Populations Aedes aegypti and Culex quinquefasciatus (Diptera: Culicidae) to
      DEET.
AB  - Knowledge on test conditions that may influence behavioral responses of
      mosquitoes is critical when excito-repellency tests are conducted. The objective
      of this study was to investigate the effect of test time differences on normal
      circadian activity and behavioral responses of field and colonized Aedes aegypti
      (L.) (=Stegomyia aegypti) and Culex quinquefasciatus Say to DEET, one of the most
      common synthetic repellent active ingredients available. Two field populations of
      Ae. aegypti and Cx. quinquefasciatus from Kanchanaburi and Nonthaburi provinces,
      respectively, and two long-standing laboratory populations, Ae. aegypti obtained
      from the U.S. Department of Agriculture, and Cx. quinquefasciatus from the
      Ministry of Public Health, Thailand, were used. Each population was exposed to
      DEET during two different periods of time (0900-1500 hours) and (2100-0300
      hours). Both field and laboratory Cx. quinquefasciatus showed marked differences
      in spatial repellent escape responses between day and nighttime periods but none
      in direct contact tests. No significant differences between day and nighttime
      testing periods were observed with field or laboratory Ae. aegypti, except a
      higher daytime escape response from noncontact DEET treatment. This study
      indicates that test time may influence the behavioral avoidance responses and is
      a potential confounder of excito-repellency evaluations. 

PMID- 26309312
TI  - Surface Polar Lipids Differ in Male and Female Phlebotomus papatasi (Diptera:
      Psychodidae).
AB  - The polar lipids on the surface of the Old World sand fly, Phlebotomus papatasi
      (Scopoli), were analyzed by high-resolution mass spectrometry. Blood-fed females
      and nonblood-fed females and males were separately analyzed and compared. The
      major polar lipids were found to be long-chain diols and fatty acids. Relatively
      high levels of diacylglycerols were found in blood-fed females and in males. A
      wide variety of lipids were found at low levels, including esters, sterols,
      monoacylglycerols, and hydroxy fatty acids. Blood-fed females had several lyso
      lipids and N-acyl amino acids that were not found on unfed females or males.
      These substances may be surfactants used in blood feeding. Heneicosenoic acid was
      found on females at more than twice the level of males, suggesting it could be a
      component of a female pheromone. Four substances were identified on males at
      twofold higher levels than on females: tetradienoic acid,
      methoxyhexadecasphinganine, butyl octadecanoate, and
      diacylglycerol(14:1/12:0/0:0). These could be short-range pheromones involved in
      courtship, and they will be further analyzed in future behavioral bioassays. 

PMID- 26309313
TI  - Seroprevalence of Rickettsia spp. in Equids and Molecular Detection of
      'Candidatus Rickettsia amblyommii' in Amblyomma cajennense Sensu Lato Ticks From
      the Pantanal Region of Mato Grosso, Brazil.
AB  - The aim of the study was to evaluate exposure of equids to rickettsial agents
      (Rickettsia rickettsii, Rickettsia parkeri, 'Candidatus Rickettsia amblyommii',
      Rickettsia rhipicephali, and Rickettsia bellii) and rickettsial infection in
      ticks of a Pantanal region of Brazil. Sera of 547 equids (500 horses and 47
      donkeys) were evaluated by indirect immunofluorescence assay. In total, 665
      adults and 106 nymphal pools of Amblyomma cajennense F. sensu lato, 10
      Dermacentor nitens Neumann ticks, and 88 larval pools of Amblyomma sp. were
      tested by polymerase chain reaction (PCR). Overall, 337 (61.6%) equids were
      reactive (titer >=64) to at least one antigen of Rickettsia spp. The prevalence
      values for Rickettsia were 66%, and the highest endpoint titers were observed for
      'Ca. R. amblyommii'. By PCR 3 (0.45%) A. cajennense s.l. females were positive
      for 'Ca. R. amblyommii'. Minimum infection rates of 0.75% for nymphs and 0.34%
      for larvae were calculated. Positive samples of ticks have had a fragment of the
      16S mitochondrial rRNA gene sequenced and sequences showed 99% identity to
      Amblyomma sculptum Berlese. This study reports a wide exposure of equids to
      Rickettsia agents, and PCR evidence of infection with 'Ca. R. amblyommii', for
      the first time, in A. sculptum. 

PMID- 26309314
TI  - Vector Competence of Selected Mosquito Species in Kenya for Ngari and Bunyamwera
      Viruses.
AB  - Bunyamwera and Ngari viruses have been isolated from a range of mosquito species
      in Kenya but their actual role in the maintenance and transmission of these
      viruses in nature remains unclear. Identification of the mosquito species
      efficient in transmitting these viruses is critical for estimating the risk of
      human exposure and understanding the transmission and maintenance mechanism. We
      determined the vector competence of, Aedes aegypti (L.), Culex quinquefasciatus
      Say, and Anopheles gambiae Giles for transmission of Bunyamwera and Ngari
      viruses. Ae. aegypti was moderately susceptible to Bunyamwera virus infection at
      days 7 and 14. Over 60% of Ae. aegypti with a midgut infection developed a
      disseminated infection at both time points. Approximately 20% more mosquitoes
      developed a disseminated infection at day 14 compared with day 7. However, while
      Ae. aegypti was incompetent for Ngari virus, An. gambiae was moderately
      susceptible to both viruses with dissemination rates more than double by day 14.
      Cx. quinquefasciatus was refractory to both Bunyamwera and Ngari viruses. Our
      results underscore the need to continually monitor emergent arboviral genotypes
      circulating within particular regions as well as vectors mediating these
      transmissions to preempt and prevent their adverse effects. The genetic mechanism
      for species specificity and vector competence owing to reassortment needs further
      investigation. 

PMID- 26309315
TI  - Use of Insecticide Delivery Tubes for Controlling Rodent-Associated Fleas in a
      Plague Endemic Region of West Nile, Uganda.
AB  - Plague is a primarily flea-borne rodent-associated zoonosis that is often fatal
      in humans. Our study focused on the plague-endemic West Nile region of Uganda
      where affordable means for the prevention of human plague are currently lacking.
      Traditional hut construction and food storage practices hinder rodent exclusion
      efforts, and emphasize the need for an inexpensive but effective host-targeted
      approach for controlling fleas within the domestic environment. Here we
      demonstrate the ability of an insecticide delivery tube that is made from
      inexpensive locally available materials to reduce fleas on domestic rodents.
      Unbaited tubes were treated with either an insecticide alone (fipronil) or in
      conjunction with an insect growth regulator [(S)-methoprene], and placed along
      natural rodent runways within participant huts. Performance was similar for both
      treatments throughout the course of the study, and showed significant reductions
      in the proportion of infested rodents relative to controls for at least 100 d
      posttreatment. 

PMID- 26309316
TI  - Isolation of Tahyna Virus (California Encephalitis Group) From Anopheles hyrcanus
      (Diptera, Culicidae), a Mosquito Species New to, and Expanding in, Central
      Europe.
AB  - Two strains of Tahyna virus (TAHV; Orthobunyavirus, Bunyaviridae) were isolated
      from 4,568 (92 pools) female Anopheles hyrcanus Pallas (Diptera, Culicidae)
      mosquitoes collected on the fishponds in South Moravia (Czechland, central
      Europe) during July-August 2013. This is the first isolation of TAHV from An.
      hyrcanus in Europe. An. hyrcanus is a species new to Czechland since 2007; its
      population density was very high in the year 2013 at these ponds. The virus
      isolation procedure was based on intracerebral inoculation of newborn mice;
      moreover, the positive pools were also tested by polymerase chain reaction and
      found to contain TAHV RNA. An. hyrcanus, feeding preferentially on mammals
      including humans, may be a new potential vector for TAHV in Europe. 

PMID- 26309317
TI  - Optimizing Collection of Anopheles gambiae s.s. (Diptera: Culicidae) in Biogents
      Sentinel Traps.
AB  - Surveillance of malaria vectors in Africa is most often accomplished using CDC
      type light traps or human landing catches (HLCs). Over the past 30 yr, a variety
      of commercial and experimental mosquito traps have been developed for residential
      mosquito control or for improved surveillance of disease vector species,
      including the BG Sentinel (BGS) trap. To optimize collection of Anopheles gambiae
      Giles using this trap, BGS traps were modified with an opening (vent) added to
      the trap base to decrease exhaust airflow. Four traps configurations were tested
      with colony-reared host-seeking female An. gambiae in free-flying laboratory
      enclosures. Six attractant treatments (three attractants: BG-Lure, Limburger
      cheese, and a blank, with and without CO2) were tested concurrently. Across all
      trap-attractant combinations, significantly more mosquitoes (P < 0.05) were
      collected in standard, unmodified traps set upright (mean: 10.0) or upside down
      (9.8) than vented traps, whether upright (5.9) or upside down (7.0). The BG-Lure
      + CO2 and Limburger Cheese + CO2 bait combinations were more attractive than the
      other attractants tested alone. All attractant combinations collected
      significantly more mosquitoes than unbaited traps. Field studies are needed to
      determine if BG-Lure + CO2- or Limburger cheese + CO2-baited BGS traps are
      comparable with HLCs in collecting host-seeking An. gambiae. 

PMID- 26309318
TI  - Molecular Detection of Leishmania in Sand Flies (Diptera: Psychodidae:
      Phlebotominae) Collected in the Caititu Indigenous Reserve of the Municipality of
      Labrea, State of Amazonas, Brazil.
AB  - Phlebotominae sand flies are of medical importance because they are vectors of
      human pathogens, such as protozoa of the genus Leishmania Ross, etiological agent
      of American cutaneous leishmaniasis (ACL). In Labrea, a municipality in the state
      of Amazonas, Brazil, ACL is primarily associated with subsistence activities,
      such as collection and extraction of forest products, undertaken by both
      indigenous and nonindigenous people. Data on ACL in indigenous populations are
      scarce, such that there is little information on the identity of the etiologic
      agent(s), reservoir host(s) and insect vector(s). The aim of this work was to
      study the sand fly fauna collected during an 8-d surveillance of different
      habitats in the Indigenous Reserve Caititu, Labrea. In total, 1,267 sand flies
      were collected in different habitats for eight consecutive days, of which 819
      (64.6%) were females and 448 (35.4%) males, from 10 genera and 32 species. The
      most abundant genera were Psychodopygus (34.3%), Trichophoromyia (22.9%), and
      Nyssomyia (15.3%). The most abundant species were Trichophoromyia ubiquitalis
      (Mangabeira) (n = 235, 18.5%), Psychodopygus davisi (Root) (n = 228, 18.0%) and
      Nyssomyia antunesi (Coutinho) (n = 135, 10.7%). Direct sequencing of polymerase
      chain reaction products demonstrated the presence of Leishmania (Leishmania)
      amazonensis and Leishmania (Viannia) braziliensis in the following species of
      sand flies: Evandromyia apurinan (Shimabukuro, Silveira, & Silva), Nyssomyia
      umbratilis (Ward & Fraiha), Nyssomyia yuilli yuilli (Young & Porter), Ps. davisi,
      Sciopemyia servulolimai (Damasceno & Causey), and Th. ubiquitalis. The presence
      of natural infection by Leishmania detected in the sand fly species investigated
      in this study suggests their possible role in the transmission cycle of ACL in
      the studied area. 

PMID- 26309319
TI  - Structural and Genetic Investigation of the Egg and First-Instar Larva of an Egg
      Laying Population of Blaesoxipha plinthopyga (Diptera: Sarcophagidae), a Species
      of Forensic Importance.
AB  - Flies in the family Sarcophagidae incubate their eggs and are known to be
      ovoviviparous (i.e., ovolarviparous), but a laboratory-maintained colony of
      Blaesoxipha plinthopyga (Wiedemann) deposited clutches of viable eggs over 10
      generations. A description of the egg and first-instar larva of this species is
      provided along with genetic data (genome size and cytochrome oxidase I
      sequences). The egg is similar to previously described eggs of other
      Sarcophagidae but differs in the configuration of the micropyle. In the first
      instar larva, the oral ridges are much more developed than has been described for
      other species. B. plinthopyga has forensic importance, and the present
      descriptive information is critical for proper case management. 

PMID- 26309320
TI  - A Comparison of Common Diets for the Continuous Culture of Adult Lucilia sericata
      (Diptera: Calliphoridae) for Forensic and Medical Entomological Applications.
AB  - Blow fly members of the family Calliphoridae, specifically Lucilia sericata
      (Meigen), have application in the fields of behavioral ecology, forensics, and
      medicine as agents for assessing ecological succession or decomposition and
      postmortem interval estimation, and for maggot debridement therapy, respectively.
      The lack of standardization of laboratory adult insect feeding, breeding, and
      rearing protocols among researchers in behavioral, medical, and forensic fields
      has become problematic. With the goal of understanding physical and physiological
      effects of diet as a baseline for future behavioral experiments, this article
      focuses on determining basic culture requirements for the adult blow fly L.
      sericata by comparing nine diets and the effects of each on survivorship and
      fecundity under controlled laboratory conditions. Percent survival, fecundity,
      and the effect of culture density were analyzed over the course of 120 d. Results
      indicate that a simple broad spectrum diet of honey water and bovine liver is the
      optimum diet for extending the life span of the flies and increasing the number
      of eggs laid per female per oviposition event, with 5-20 female flies being the
      optimum number per culture vessel. This culture protocol is simple to follow, can
      be easily incorporated into current behavioral, forensic, and medical entomology
      research programs, and the dietary components are readily available across
      diverse geographic areas. 

PMID- 26309321
TI  - Prevalence of Candidatus Rickettsia tarasevichiae-Like Bacteria in Ixodid Ticks
      at 13 Sites on the Chinese-Russian Border.
AB  - To investigate the likely source population and candidate vectors of Candidatus
      Rickettsia tarasevichiae, the prevalence of this bacteria was quantified in
      specimens of four tick species that mainly parasitize humans collected from 13
      sites along the Chinese-Russian border. The presence of the bacteria was
      determined by detecting its specific citrate synthase (gltA) partial gene and
      outer membrane protein A (ompA) partial gene. Only Ixodes persulcatus Schulze was
      found to be naturally infected with C. R. tarasevichiae, which had an overall
      prevalence of 1.53% in both sexes. C. R. tarasevichiae is an emerging, tick-borne
      human pathogen and this finding may partially explain recent human cases of
      infection by this organism in China. Public health authorities should be aware of
      the potential risk posed by the transmission of this bacterium to humans by
      ticks. 

PMID- 26309322
TI  - Effect of Temperature on Feeding Period of Larval Blacklegged Ticks (Acari:
      Ixodidae) on Eastern Fence Lizards.
AB  - Ambient temperature can influence tick development time, and can potentially
      affect tick interactions with pathogens and with vertebrate hosts. We studied the
      effect of ambient temperature on duration of attachment of larval blacklegged
      ticks, Ixodes scapularis Say, to eastern fence lizards, Sceloporus undulatus
      (Bosc & Daudin). Feeding periods of larvae that attached to lizards under
      preferred temperature conditions for the lizards (WARM treatment: temperatures
      averaged 36.6 degrees C at the top of the cage and 25.8 degrees C at the bottom,
      allowing behavioral thermoregulation) were shorter than for larvae on lizards
      held under cool conditions (COOL treatment temperatures averaged 28.4 degrees C
      at top of cage and 24.9 degrees C at the bottom). The lizards were infested with
      larvae four times at roughly monthly intervals. Larval numbers successfully
      engorging and dropping declined and feeding period was longer after the first
      infestation. 

PMID- 26309323
TI  - Influence of Bloodmeal Source on Reproductive Output of the Potential West Nile
      Vector, Culex theileri (Diptera: Culicidae).
AB  - Culex theileri Theobald (Diptera: Culicidae) has a wide Afrotropical, southern
      Palaearctic, northern Oriental, and European distribution. It is mainly
      considered as a mammophilic mosquito and also feeds on birds and serves as a
      vector for various zoonotic diseases including West Nile virus. Despite its broad
      distribution and evidence indicating that Cx. theileri is a competent vector of
      human and domestic animal pathogens, basic biological and ecological features of
      this species have not been well investigated. We evaluated the impact of
      bloodmeal source (human, chicken, cow, and a double bloodmeal such as human and
      cow or chicken and cow and mixed bloodmeals [cow, chicken, and human] via
      artificial feeding) on fecundity, hatching rates, developmental times, and
      viability from egg to adult for laboratory colonized Cx. theileri. Fecundity in
      mosquitoes that took a chicken bloodmeal, a double bloodmeal and mixed bloodmeals
      was significantly higher than in females fed on a single cow or single human
      blood. This is the first study about the bloodmeal sources effect on laboratory
      reared Cx. theileri populations and these findings contribute to our
      understanding of the impact of bloodmeal source on reproduction in Cx. theileri.
      As it is known that Cx. theileri is a vector for West Nile virus, the potential
      impacts of bloodmeal source on virus transmission are discussed. 

PMID- 26309324
TI  - Ultrastructure of Presumed "Candidatus Rickettsia Andeanae" in Amblyomma
      maculatum (Acari: Ixodidae).
AB  - Amblyomma maculatum Koch, 1844 (also known as the Gulf Coast tick) is found in
      parts of the Americas, including the central and southern United States. Its
      primary importance is as the vector of Rickettsia parkeri, a spotted fever group
      rickettsia that causes an illness similar to, but milder than, Rocky Mountain
      spotted fever. A second spotted fever group rickettsia, "Candidatus Rickettsia
      andeanae," was detected in Gulf Coast ticks approximately 10 yr ago. However, the
      significance of this organism, including pathogenicity, has not yet been well
      characterized. Here, we use transmission electron microscopy to describe bacteria
      within the tissues of A. maculatum ticks that were positive by polymerase chain
      reaction assay for "Ca. R. andeanae." In ultrathin sections of unfed A. maculatum
      adult females, we found evidence of bacteria with morphological features
      consistent with spotted fever group rickettsiae, including small size (~0.3 by
      0.9 MUm), a halo zone (electron-lucent layer around the bacterium), and a
      trilaminar cell wall. In female ticks, bacteria were present in granular salivary
      glands and ducts, foregut, Malpighian tubules, nerve trunks, and reproductive
      tissue. These findings demonstrate evidence of "Ca. R. andeanae" in situ and
      contribute to our understanding of this novel rickettsia in A. maculatum. 

PMID- 26309325
TI  - ESA Sustaining Associates.

PMID- 26309328
TI  - CUMULATIVE KEY WORD INDEX Journal of Medical Entomology Volume 51, 2014.

PMID- 26309329
TI  - Correction for Voinnet et al., Suppression of gene silencing: A general strategy
      used by diverse DNA and RNA viruses of plants.

PMID- 26309330
TI  - Reliability of the 505 Change-of-Direction Test in Netball Players.
AB  - PURPOSE: To determine the reliability of the 505 change-of-direction (COD) test
      performed with both a stationary and a flying start. METHODS: Fifty-two female
      netball players (age 23.9 +/- 5.4 y, height 169.9 +/- 3.3 cm, body mass 65.2 +/-
      4.6 kg) performed 6 trials of the 505 COD test, 3 with a flying start and 3 with
      a stationary start, once per week over a 4-wk period to determine within- and
      between-sessions reliability. RESULTS: Testing revealed high within-session
      reliability for the stationary start (ICC = .96-.97) and for the flying start
      (ICC = .90-.97). Similarly, both the stationary start (ICC = .965) and the flying
      start (ICC = .951) demonstrated high reliability between sessions, although
      repeated-measures analysis of variance (P < .001) revealed learning effects
      between sessions for both tests. Performances stabilized on day 2 for the static
      start and on day 3 for the flying start. CONCLUSIONS: The 505 COD test is a
      reliable test in female netball players, with either a stationary or flying
      start. Smallest detectable differences of 3.91% and 3.97% for the stationary
      start and the flying start, respectively, allow practitioners to interpret
      whether changes in time taken to complete the 505 COD test reflect genuine
      improvements in performance or are measurement errors. It is suggested that 1 d
      of familiarization testing be performed for the stationary start and 2 d of
      familiarization for the flying start, to minimize learning effects.

PMID- 26309331
TI  - The Influence of In-Season Training Loads on Injury Risk in Professional Rugby
      Union.
AB  - PURPOSE: To explore the association between in-season training-load (TL) measures
      and injury risk in professional rugby union players. METHODS: This was a 1-season
      prospective cohort study of 173 professional rugby union players from 4 English
      Premiership teams. TL (duration * session-RPE) and time-loss injuries were
      recorded for all players for all pitch- and gym-based sessions. Generalized
      estimating equations were used to model the association between in-season TL
      measures and injury in the subsequent week. RESULTS: Injury risk increased
      linearly with 1-wk loads and week-to-week changes in loads, with a 2-SD increase
      in these variables (1245 AU and 1069 AU, respectively) associated with odds
      ratios of 1.68 (95% CI 1.05-2.68) and 1.58 (95% CI 0.98-2.54). When compared with
      the reference group (<3684 AU), a significant nonlinear effect was evident for 4
      wk cumulative loads, with a likely beneficial reduction in injury risk associated
      with intermediate loads of 5932-8651 AU (OR 0.55, 95% CI 0.22-1.38) (this range
      equates to around 4 wk of average in-season TL) and a likely harmful effect
      evident for higher loads of >8651 AU (OR 1.39, 95% CI 0.98-1.98). CONCLUSIONS:
      Players had an increased risk of injury if they had high 1-wk cumulative loads
      (1245 AU) or large week-to-week changes in TL (1069 AU). In addition, a U-shaped
      relationship was observed for 4-wk cumulative loads, with an apparent increase in
      risk associated with higher loads (>8651 AU). These measures should therefore be
      monitored to inform injury-risk-reduction strategies.

PMID- 26309332
TI  - Use of CR100 Scale for Session Rating of Perceived Exertion in Soccer and Its
      Interchangeability With the CR10.
AB  - PURPOSE: To examine the construct validity of the session rating perceived
      exertion (s-RPE) assessed with the Borg CR100 scale to measure training loads in
      elite soccer and to examine if the CR100 is interchangeable and can provide more
      accurate ratings than the CR10 scale. METHODS: Two studies were conducted. The
      validity of the CR100 was determined in 19 elite soccer players (age 28 +/- 6 y,
      height 180 +/- 7 cm, body mass 77 +/- 6 kg) during training sessions through
      correlations with the Edwards heart-rate method (study 1). The interchangeability
      with CR10 was assessed in 78 soccer players (age 19.3 +/- 4.1 y, height 178 +/-
      5.9 cm, body mass 71.4 +/- 6.1 kg) through the Bland-Altman method and
      correlations between change scores in different sessions. To examine whether the
      CR100 is more finely graded than the CR10, the proportions of responses
      corresponding to the verbal expressions were calculated (study 2). RESULTS:
      Individual correlations between the Edwards method and s-RPE were large to very
      large (.52-.85). The mean difference between the 2 scales was -0.3 +/- 0.33 AU
      (90% CI -0.41 to -0.29) with 95% limits of agreements (0.31 to -0.96 AU).
      Correlations between scales and between-changes scores were nearly perfect (.95
      and .91-.98). Ratings corresponding to the verbal anchors were 49% in CR10 and
      26% in CR100. CONCLUSIONS: The CR100 is valid for assessing the training load in
      elite soccer players. It can be used interchangeably with the CR10 and may
      provide more-precise measures of exercise intensity.

PMID- 26309333
TI  - Selectivity and Mechanism of Thermal Decomposition of beta-diketones on ZnO
      Powder.
AB  - The thermal chemistry of beta-diketones underlies a number of catalytic processes
      related both to the catalytic reactions yielding commodity chemicals and to the
      production of supported transition metal catalysts themselves. The mechanisms of
      decomposition during thermal transformation of three beta-diketones,
      acetylacetone (acacH), 1,1,1-trifluoroacetylacetone (tfacH), and 1,1,1,5,5,5
      hexafluoroacetylacetone (hfacH), were studied on ZnO powder surface using Fourier
      transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS),
      and Density functional theory (DFT) computational investigation. The initial O-H
      dissociation leads to the formation of corresponding beta-diketonates in all the
      cases investigated. These diketonates are important surface intermediates that
      can be generated in a controlled manner in these experiments. The presence on the
      C-CF3 entity determines the preferred thermal decomposition pathways, as the C-C
      bond in this group starts to react with a surface of ZnO around 400 K, followed
      by immediate decomposition of the resulting CF3 group. Above 600 K, the presence
      of the CF3-substituent leads to the formation of ketene-like structures observed
      by vibrational spectroscopy. The reaction mechanisms examined with the help of
      DFT calculations are correlated with vibrational signatures of the species
      produced and with the F-containing species recorded by XPS.

PMID- 26309334
TI  - Studies toward the AB ring system of the tetrapetalone natural products.
AB  - Synthetic efforts toward the rapid assembly of the AB ring system of the
      tetrapetalones is described. Key to this work was the use of [3+2]
      cycloaddition/oxidative extrusion methodology to furnish functionalized aryl
      enones. The Nazarov cyclization of these substrates was examined, and optimized
      to generate the AB ring carbon skeleton. Then, Pd-catalyzed cross-coupling were
      conducted, and conditions were identified that enabled installation of the
      requisite C14-N bond.

PMID- 26309335
TI  - Preparation of 1-Tosyloxy-4-Substituted-2-butenes Using Ag(I) Salts.
AB  - The trans-fluoro-2-butenyl group has been previously utilized as an N-substituent
      on several nortropanes for imaging the dopamine transporter with positron
      emission tomography. We report here a simplified and shorter synthesis of trans-1
      tosyloxy-4-substituted-2-butenes using Ag(I) salts. This methodology was also
      applied to the synthesis of the cis-isomers. Furthermore, these procedures allow
      for the recovery of the majority of the Ag(I) ions.

PMID- 26309336
TI  - Synthesis of a reactive oxygen species responsive heterobifunctional thioketal
      linker.
AB  - A new heterobifunctional reactive oxygen species (ROS) responsive thioketal
      linker and its synthesis are described. This linker allows for developing new ROS
      responsive agents with two distinct functionalities using universal
      bioconjugation methods. The reaction kinetics of the thioketal cleavage in the
      presence of ROS is also described.

PMID- 26309337
TI  - An Investigation of Hope and Context.
AB  - One of the tenets of community psychology is examining psychological phenomena in
      context, and our studies explored the relationship between hope and context among
      individuals in recovery for substance use disorders. Study 1 involved 595
      participants who resided in 90 recovery homes. We found that context, as house
      effects, was salient in residents' perceptions of hope, suggesting that the
      context of recovery homes-- their configurations and dynamics-- may play a role
      in an individual's future perspective. Study 2 involved 102 recovering adults.
      Findings indicated that one's perceived context (i.e., opportunities, choices, &
      obstacles) was related to not only one's self-reported levels of hope, but one's
      perception of hope for others. Approximately 50% of an individual's hopefulness
      was explained by contextual factors, thus suggesting that system level effects
      are critical to an individual's hopefulness. The finding that context was
      predictive of hopefulness suggests that a community psychology perspective on
      feelings of hope is critical, especially for individuals in substance use
      recovery. Implications regarding the importance of hope and context for
      ecological research and contextual influences on behavior change are discussed.

PMID- 26309338
TI  - The right to die with dignity and conscientious objection.

PMID- 26309339
TI  - Variations in the anatomical relationship between the common carotid artery and
      the internal jugular vein: an ultrasonographic study.
AB  - INTRODUCTION: The internal jugular vein locates anterior or anterolateral to the
      common carotid artery in two-thirds of the subjects studied by ultrasound when
      the head is in a rotated position. AIM: To identify variables associated with the
      anterior location of the internal jugular vein. METHODS: Ultrasound examinations
      were performed with the patients in the supine position, with the head rotated to
      the opposite side. The proximal third of the neck was visualized transversely
      with a 7.5-mHz transducer. The relationship between the vessels was described in
      accordance with the proportion of the artery overlapped by the vein. Univariate
      comparisons and a multivariate analysis of potential variables that may affect
      the anatomic relationships were performed. RESULTS: Seventy-eight patients were
      included, 44 of whom were men. The patients' ages ranged from 17 to 90 years
      (median 64.0, interquartile range 41-73). The right and left sides were studied
      75 and 73 times, respectively. The vein was located lateral to the artery in
      24.3% (95%CI= 17.4-32.2) of the studies, anterolateral in 33.8% (95%CI= 26.2
      41.4) and anterior in 41.9% (95%CI= 33.9-49.8). The multivariate analysis
      identified age group (OR= 3.7, 95% CI 2.1-6.4) and, less significantly, the left
      side (OR= 1.7, 95%CI= 0.8-3.5) and male gender (OR= 1.2, 95%CI= 0.6-2.7) as
      variables associated with the anterior position of the vein. CONCLUSION: The
      anterior position of the internal jugular vein relative to the common carotid
      artery increases gradually with age. Additionally, left-sided localization and
      male sex further increased the probability of an anterior position.

PMID- 26309340
TI  - Introduction of software tools for epidemiological surveillance in infection
      control in Colombia.
AB  - INTRODUCTION: Healthcare-Associated Infections (HAI) are a challenge for patient
      safety in the hospitals. Infection control committees (ICC) should follow CDC
      definitions when monitoring HAI. The handmade method of epidemiological
      surveillance (ES) may affect the sensitivity and specificity of the monitoring
      system, while electronic surveillance can improve the performance, quality and
      traceability of recorded information. OBJECTIVE: To assess the implementation of
      a strategy for electronic surveillance of HAI, Bacterial Resistance and
      Antimicrobial Consumption by the ICC of 23 high-complexity clinics and hospitals
      in Colombia, during the period 2012-2013. METHODS: An observational study
      evaluating the introduction of electronic tools in the ICC was performed; we
      evaluated the structure and operation of the ICC, the degree of incorporation of
      the software HAI Solutions and the adherence to record the required information.
      RESULTS: Thirty-eight percent of hospitals (8/23) had active surveillance
      strategies with standard criteria of the CDC, and 87% of institutions adhered to
      the module of identification of cases using the HAI Solutions software. In
      contrast, compliance with the diligence of the risk factors for device-associated
      HAIs was 33%. CONCLUSIONS: The introduction of ES could achieve greater adherence
      to a model of active surveillance, standardized and prospective, helping to
      improve the validity and quality of the recorded information.

PMID- 26309341
TI  - Increasing collaboration between health professionals: Clues and challenges.
AB  - BACKGROUND: Scholars have recently started to pay more attention in the potential
      of the inter-professional relationship between general practitioners and
      specialists to improve outcomes, through consideration given to the effect on
      prescribing practices. However, more empirical research is needed. OBJECTIVE: To
      explore inter-professional network factors that may explain effects on General
      Practitioners prescription behaviours. METHODS: A qualitative study was conducted
      in an integrated diabetes care program. Data was collected through semi
      structured interviews from 16 health practices and a hospital diabetes clinic,
      using a convenience sample of general practitioners, practices nurses, diabetes
      nurse specialists and endocrinologists. A conceptual mapping was performed to
      identify factors underlying networks and effects on patient outcomes. RESULTS:
      Four themes with their concepts emerged from the conceptual map. These
      demonstrated the need for building effective channels of communication to share
      experience and knowledge timely in diabetes care. Communication, collaboration
      and coordination are critical factors to influence prescription behaviours within
      primary and secondary care. CONCLUSIONS: conceptual mapping allowed understanding
      factors that might explain how links between health professionals can improve
      patient outcomes at the primary and secondary care interface.

PMID- 26309342
TI  - Second toe-to-hand transplantation: A surgical option for hand amputations.
AB  - BACKGROUND: The toe to hand transplantation is a method of reconstruction on the
      unique or multiple amputations of the fingers. It can be used the whole toe or
      with certain modifications as a wrap-around flap from the big toe or fingertip.
      It is a widely accepted option for the thumb. METHODS: It is a series of patients
      with amputation of one or more fingers of the hand were operated with second toe
      to hand transplantation. The survival was evaluated and the sensory recovery by 2
      point discrimination. RESULTS: We practiced 12 transplants, 8 thumb, and 4 in
      other fingers. Ten were adults and two children. All transplants survived. Two
      patients required tenolysis flexor. The sensibility was recovered with good 2
      point discrimination of 8 mm. DISCUSSION: In the more proximal finger
      amputations, a second toe is the most appropriate, with lower morbidity of the
      donor site. The rates of success are between 95 to 100%. We had a success rate of
      100%. The resulting defect is in the foot is minimum when the second toe was
      used. The decision to use one of these techniques depends on the decision and
      transplant surgeon training. We always used the second toe for transfers to the
      hand, considering that it will be thinner than the original thumb; our patients
      had no complaint about the appearance. CONCLUSION: Toe-to-hand transplantation is
      a good technique, providing a very good aesthetic appearance and allowing the
      recovery of sensitivity. The defect that is created in the foot does not produce
      significant aesthetic and functional alterations.

PMID- 26309343
TI  - C677T (RS1801133 ) MTHFR gene polymorphism frequency in a colombian population.
AB  - INTRODUCTION: Abnormal levels of the enzyme methylenetetrahydrofolate reductase
      (MTHFR) are associated with an increased risk of both cardiovascular and
      cerebrovascular disease and higher concentrations of homocysteine. Abnormal
      levels are also related to birth defects, pregnancy complications, cancer and
      toxicity to methotrexate (MTX). Polymorphisms of MTHFR affect the activity of the
      enzyme. Genetic associations have been related to treatment efficacy. OBJECTIVE:
      To establish the frequency of the C> T polymorphism at nucleotide 677 of the
      MTHFR gene in a group of Colombian individuals. METHODS: Data from
      pharmacogenetic microarrays that include MTX sensibility-associated polymorphisms
      were retrospectively collected (Pathway Genomics((r))). The frequency of the C> T
      MTHFR rs1801133 marker polymorphism was analyzed. RESULTS: Microarray data from
      68 men and 84 women were analyzed. Comparisons of genotype C/C vs. C/T and T/T
      were statistically significantly different (p= 0.00, p= 0.026, respectively), as
      were C/T and T / T (p= 0.0001). CONCLUSIONS: Results for the C/C and C/T
      genotypes in a Colombian population are similar to other previously studied
      groups of healthy subjects. Subjects from our population might be at risk of
      developing diseases associated with MTHFR polymorphisms and might present
      toxicity and adverse effects if treated with MTX, which suggests the need to
      evaluate therapeutic alternatives based on individual pharmacogenetic studies.

PMID- 26309344
TI  - Adult patent ductus arteriosus complicated by endocarditis and hemolytic anemia.
AB  - An adult with a large patent ductus arteriosus may present with fatigue, dyspnea
      or palpitations or in rare presentation with endocarditis. The case illustrated
      unique role of vegetation of endocarditis in hemolytic anemia in adult with
      patent ductus arteriosus (PDA). Despite treatment of endocarditis with complete
      course of appropriate antibiotic therapy and normality of C- reactive protein,
      erythrocyte sedimentation rate and leukocytosis and wellness of general
      condition, transthoracic echocardiography revealed large vegetation in PDA lumen,
      surgical closure of PDA completely relieved hemolysis, and fragmented red cell
      disappeared from peripheral blood smear. The 3-month follow-up revealed complete
      occlusion of PDA and abolishment of hemolytic anemia confirmed by clinical and
      laboratory examination. 

PMID- 26309345
TI  - Adrenal venous sampling in a patient with adrenal Cushing syndrome.
AB  - The primary bilateral macronodular adrenal hyperplasia or the independent
      adrenocorticotropic hormone bilateral nodular adrenal hyperplasia is a rare cause
      hypercortisolism, its diagnosis is challenging and there is no clear way to
      decide the best therapeutic approach. Adrenal venous sampling is commonly used to
      distinguish the source of hormonal production in patients with primary
      hyperaldosteronism. It could be a useful tool in this context because it might
      provide information to guide the treatment. We report the case of a patient with
      ACTH independent Cushing syndrome in whom the use of adrenal venous sampling with
      some modifications radically modified the treatment and allowed the diagnosis of
      a macronodular adrenal hyperplasia. 

PMID- 26309346
TI  - Bully/Victim Profiles' Differential Risk for Worsening Peer Acceptance: The Role
      of Friendship.
AB  - Study aims were to: (1) evaluate the association between bully/victim profiles,
      derived via latent profile analysis (LPA), and changes in peer acceptance from
      the fall to spring of 7th grade, and (2) investigate the likelihood of
      friendlessness, and the protective function of mutual friendship, among
      identified profiles. Participants were 2,587 7th graders; peer nomination and
      rating-scale data were collected in the fall and spring. Four profiles, including
      bullies, victims, bully-victims, and uninvolved adolescents, were identified at
      each time point. Findings showed that for victims, more so than for bullies and
      uninvolved profiles, acceptance scores worsened over time. Results further
      revealed that bully-victim and victim profiles included a greater proportion of
      friendless youth relative to the bully profile, which, in turn, contained a
      greater proportion of friendless adolescents than the uninvolved profile.
      Findings also provided evidence for the buffering role of friendship among all
      bully/victim profiles and among bully-victims especially.

PMID- 26309347
TI  - An agent-based model to simulate tsetse fly distribution and control techniques:
      a case study in Nguruman, Kenya.
AB  - BACKGROUND: African trypanosomiasis, also known as "sleeping sickness" in humans
      and "nagana" in livestock is an important vector-borne disease in Sub-Saharan
      Africa. Control of trypanosomiasis has focused on eliminating the vector, the
      tsetse fly (Glossina, spp.). Effective tsetse fly control planning requires
      models to predict tsetse population and distribution changes over time and space.
      Traditional planning models have used statistical tools to predict tsetse
      distributions and have been hindered by limited field survey data.
      METHODOLOGY/RESULTS: We developed an Agent-Based Model (ABM) to provide timing
      and location information for tsetse fly control without presence/absence training
      data. The model is driven by daily remotely-sensed environment data. The model
      provides a flexible tool linking environmental changes with individual biology to
      analyze tsetse control methods such as aerial insecticide spraying, wild animal
      control, releasing irradiated sterile tsetse males, and land use and cover
      modification. SIGNIFICANCE: This is a bottom-up process-based model with freely
      available data as inputs that can be easily transferred to a new area. The tsetse
      population simulation more closely approximates real conditions than those using
      traditional statistical models making it a useful tool in tsetse fly control
      planning.

PMID- 26309348
TI  - NIOSH Manual of Analytical Methods 5th Edition and Harmonization of Occupational
      Exposure Monitoring.
AB  - The NIOSH Manual of Analytical Methods (NMAM: www.cdc.gov/niosh/nmam) is a
      collection of methods for sampling and analysis of contaminants in workplace air
      (or surfaces) and in the blood and urine of workers who are occupationally
      exposed. NIOSH methods are used worldwide for occupational exposure assessment to
      chemical and biological agents. These methods have been developed or adapted by
      NIOSH and/or its partners and have been evaluated according to established
      experimental protocols and performance criteria. NMAM also includes associated
      chapters on quality assurance, sampling guidance, instrumentation, aerosol
      measurement, gas and vapor monitoring, portable monitoring devices, and so forth.
      Often NIOSH methods are developed in coordination with voluntary consensus
      standards organizations such as ASTM International, the Comite Europeen de
      Normalisation (European Committee for Standardization, CEN) and the International
      Organization for Standardization (ISO). Efforts to harmonize NIOSH methods with
      relevant consensus standards procedures are of particular interest and are
      highlighted. NIOSH also has a formal Memorandum of Understanding (MOU) with the
      Institut fur Arbeitsschutz der Deutschen Geseltzlichen Unfallversicherung
      (Institute for Occupational Safety and Health of the German Social Accident
      Insurances, IFA), whereby NIOSH is adopting selected IFA methods and vice-versa.
      An overview of recent research and technology transfer activities relating to
      NMAM methods is provided, with selected examples in applications to exposure
      science, notably workplace air monitoring. Included in the discussion are newly
      approved methods and those under development, as well as needs for new methods
      and updates. Of particular interest are recent NIOSH recommendations and
      associated research on air samplers used for sampling and analysis of airborne
      particles.

PMID- 26309349
TI  - Iron deficiency anemia in celiac disease.
AB  - Iron is an important micronutrient that may be depleted in celiac disease. Iron
      deficiency and anemia may complicate well-established celiac disease, but may
      also be the presenting clinical feature in the absence of diarrhea or weight
      loss. If iron deficiency anemia occurs, it should be thoroughly evaluated, even
      if celiac disease has been defined since other superimposed causes of iron
      deficiency anemia may be present. Most often, impaired duodenal mucosal uptake of
      iron is evident since surface absorptive area in the duodenum is reduced, in
      large part, because celiac disease is an immune-mediated disorder largely focused
      in the proximal small intestinal mucosa. Some studies have also suggested that
      blood loss may occur in celiac disease, sometimes from superimposed small
      intestinal disorders, including ulceration or neoplastic diseases, particularly
      lymphoma. In addition, other associated gastric or colonic disorders may be
      responsible for blood loss. Rarely, an immune-mediated hemolytic disorder with
      increased urine iron loss may occur that may respond to a gluten-free diet.
      Reduced expression of different regulatory proteins critical in iron uptake has
      also been defined in the presence and absence of anemia. Finally, other rare
      causes of microcytic anemia may occur in celiac disease, including a
      sideroblastic form of anemia reported to have responded to a gluten-free diet. 

PMID- 26309350
TI  - Oral Campylobacter species: Initiators of a subgroup of inflammatory bowel
      disease?
AB  - In recent years, a number of studies detected a significantly higher prevalence
      of Campylobacter species such as Campylobacter concisus (C. concisus) in
      intestinal biopsies and fecal samples collected from patients with inflammatory
      bowel disease (IBD) compared to controls. Most of these Campylobacter species are
      not of zoonotic origin but are human oral Campylobacter species. Bacterial
      species usually cause diseases in the location where they colonize. However, C.
      concisus and other oral Campylobacter species are associated with IBD occurring
      at the lower parts of the gastrointestinal tract, suggesting that these
      Campylobacter species may have unique virulence factors that are expressed in the
      lower parts of the gastrointestinal tract. 

PMID- 26309351
TI  - Treatment of hemorrhoids: A coloproctologist's view.
AB  - Hemorrhoids is recognized as one of the most common medical conditions in general
      population. It is clinically characterized by painless rectal bleeding during
      defecation with or without prolapsing anal tissue. Generally, hemorrhoids can be
      divided into two types: internal hemorrhoid and external hemorrhoid. External
      hemorrhoid usually requires no specific treatment unless it becomes acutely
      thrombosed or causes patients discomfort. Meanwhile, low-graded internal
      hemorrhoids can be effectively treated with medication and non-operative measures
      (such as rubber band ligation and injection sclerotherapy). Surgery is indicated
      for high-graded internal hemorrhoids, or when non-operative approaches have
      failed, or complications have occurred. Although excisional hemorrhoidectomy
      remains the mainstay operation for advanced hemorrhoids and complicated
      hemorrhoids, several minimally invasive operations (including Ligasure
      hemorrhoidectomy, doppler-guided hemorrhoidal artery ligation and stapled
      hemorrhoidopexy) have been introduced into surgical practices in order to avoid
      post-hemorrhiodectomy pain. This article deals with some fundamental knowledge
      and current treatment of hemorrhoids in a view of a coloproctologist - which
      includes the management of hemorrhoids in complicated situations such as
      hemorrhoids in pregnancy, hemorrhoids in immunocompromised patients, hemorrhoids
      in patients with cirrhosis or portal hypertension, hemorrhoids in patients having
      antithrombotic agents, and acutely thrombosed or strangulated hemorrhoids. Future
      perspectives in the treatment of hemorrhoids are also discussed. 

PMID- 26309352
TI  - Lynch syndrome and Lynch syndrome mimics: The growing complex landscape of
      hereditary colon cancer.
AB  - Hereditary non-polyposis colorectal cancer (HNPCC) was previously synonymous with
      Lynch syndrome; however, identification of the role of germline mutations in the
      DNA mismatch repair (MMR) genes has made it possible to differentiate Lynch
      syndrome from other conditions associated with familial colorectal cancer (CRC).
      Broadly, HNPCC may be dichotomized into conditions that demonstrate defective DNA
      MMR and microsatellite instability (MSI) vs those conditions that demonstrate
      intact DNA MMR. Conditions characterized by MMR deficient CRCs include Lynch
      syndrome (germline MMR mutation), Lynch-like syndrome (biallelic somatic MMR
      mutations), constitutional MMR deficiency syndrome (biallelic germline MMR
      mutations), and sporadic MSI CRC (somatic biallelic methylation of MLH1). HNPCC
      conditions with intact DNA MMR associated with familial CRC include polymerase
      proofreading associated polyposis and familial colorectal cancer type X. Although
      next generation sequencing technologies have elucidated the genetic cause for
      some HNPCC conditions, others remain genetically undefined. Differentiating
      between Lynch syndrome and the other HNPCC disorders has profound implications
      for cancer risk assessment and surveillance of affected patients and their at
      risk relatives. Clinical suspicion coupled with molecular tumor analysis and
      testing for germline mutations can help differentiate the clinical mimicry within
      HNPCC and facilitate diagnosis and management. 

PMID- 26309353
TI  - Role of phytochemicals in colorectal cancer prevention.
AB  - Although the incidence of colorectal cancer (CRC) has been declining in recent
      decades, it remains a major public health issue as a leading cause of cancer
      mortality and morbidity worldwide. Prevention is one milestone for this disease.
      Extensive study has demonstrated that a diet containing fruits, vegetables, and
      spices has the potential to prevent CRC. The specific constituents in the dietary
      foods which are responsible for preventing CRC and the possible mechanisms have
      also been investigated extensively. Various phytochemicals have been identified
      in fruits, vegetables, and spices which exhibit chemopreventive potential. In
      this review article, chemopreventive effects of phytochemicals including
      curcumin, polysaccharides (apple polysaccharides and mushroom glucans), saponins
      (Paris saponins, ginsenosides and soy saponins), resveratrol, and quercetin on
      CRC and the mechanisms are discussed. This review proposes the need for more
      clinical evidence for the effects of phytochemicals against CRC in large trials.
      The conclusion of the review is that these phytochemicals might be therapeutic
      candidates in the campaign against CRC. 

PMID- 26309354
TI  - Endoscopic full-thickness resection: Current status.
AB  - Conventional endoscopic resection techniques such as endoscopic mucosal resection
      or endoscopic submucosal dissection are powerful tools for treatment of
      gastrointestinal neoplasms. However, those techniques are restricted to
      superficial layers of the gastrointestinal wall. Endoscopic full-thickness
      resection (EFTR) is an evolving technique, which is just about to enter clinical
      routine. It is not only a powerful tool for diagnostic tissue acquisition but
      also has the potential to spare surgical therapy in selected patients. This
      review will give an overview about current EFTR techniques and devices. 

PMID- 26309355
TI  - Local excision by transanal endoscopic surgery.
AB  - Transanal endoscopic surgery (TES) consists of a series of anorectal surgical
      procedures using different devices that are introduced into the anal canal. TES
      has been developed significantly since it was first used in the 1980s. The key
      point for the success of these techniques is how accurately patients are
      selected. The main indication was the resection of endoscopically unresectable
      adenomas. In recent years, these techniques have become more widespread which has
      allowed them to be applied in conservative rectal procedures for both benign
      diseases and selected cases of rectal cancer. For more advanced rectal cancers it
      should be considered palliative or, in some controlled trials, experimental. The
      role of newer endoscopic techniques available has not yet been defined. TES may
      allow for new strategies in the treatment of rectal pathology, like transanal
      natural orifice transluminal endoscopic surgery or total mesorectal excision. 

PMID- 26309356
TI  - Perspectives in the treatment of pancreatic adenocarcinoma.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is an incurable lethal disease whose
      incidence rate is growing. There is no effective screening for detection of early
      stage tumors and, in most cases, PDAC is diagnosed at advanced disease stages,
      when radical pancreatic resection is not possible. The aggressive nature of
      pancreatic tumor cells lies in the complex genetic mechanisms behind their
      uncontrolled capability to grow and metastasize, which involve essential adaptive
      changes in cellular metabolism, signaling, adhesion and immunoediting. In
      addition, PDAC cells promote a dense functional stroma that facilitates tumor
      resistance to chemotherapy and radiation. During the last two decades,
      gemcitabine has been the reference for the systemic treatment of PDAC. However,
      recently, a regimen combining fluorouracil, irinotecan, oxaliplatin, and
      leucovorin (FOLFIRINOX) and another combining albumin-bound paclitaxel with
      gemcitabine have shown clear therapeutic advantage in advanced PDAC, with
      survival outcomes of 11.3 and 8.5 mo on phase III trials, respectively, over
      single-agent gemcitabine. With the pending issue of their higher toxicities,
      these regimens set the reference for ongoing and future clinical studies in
      advanced PDAC. In addition, the efficacy of oral fluoropyrimidine (S-1) has been
      well documented in Asiatic PDAC patients. The development of therapeutic
      approaches other than cytotoxic drugs has proven difficult in the past, with only
      one drug (erlotinib) approved to date. Besides, a number of agents targeting
      signaling pathways in tumor or stroma cells are being investigated. Likewise,
      immunotherapies that target PDAC in various ways are the subject of a number of
      clinical trials. The search for reliable biomarkers with diagnostic and
      prognostic value using genomics and mass spectrometry methods may facilitate
      monitoring and refinement of therapies. This review focuses on current
      understanding of the pathogenesis of PDAC and the latest developments in the
      treatment of advanced PDAC. 

PMID- 26309357
TI  - Reciprocal impact of host factors and Helicobacter pylori genotypes on gastric
      diseases.
AB  - AIM: To assess the impact of Helicobacter pylori (H. pylori) genotypes and
      patient age and sex on the development of gastric diseases. METHODS: H. pylori
      infected patients (n = 233) referred to the endoscopy unit at Tehran University
      of Medical Sciences (Tehran, Iran) were diagnosed with chronic gastritis (CG),
      gastric ulcer (GU), or duodenal ulcer (DU). Brucella blood agar was used for
      biopsy cultures and H. pylori isolation under microaerobic conditions. H. pylori
      isolates were confirmed with biochemical tests and through amplification of the
      16S rRNA gene. DNA was extracted from fresh cultures of the H. pylori isolates
      and used for amplification of vacA alleles and the cagA gene. Statistical
      analysis was performed to determine the association between H. pylori genotypes,
      age (< 40 years vs > 40 years) and sex of the patient, and gastric diseases.
      RESULTS: CG was the most prevalent gastric disease (113/233; 48.5%), compared to
      GU (64/233; 27.5%) and DU (56/233; 24%). More patients were male, and gastric
      diseases were more frequent in patients > 40 years (P < 0.05). The percentage of
      CG and GU patients that were male and female did not show a significant
      difference; however DU was more common in males (P < 0.05). Interestingly, a
      diagnosis of CG in patients > 40 years was more common in females (18.5%) than
      males (11.6%) (P = 0.05), whereas a diagnosis of GU or DU in patients > 40 years
      was more frequent in males (14.6% vs 10.7% and 12.4% vs 4.3%, respectively).
      Overall, genotyping of the H. pylori isolates revealed that the vacA s1 (82%),
      vacA m2 (70%), and cagA (+) (72.5%) alleles were more frequent than vacA s2
      (18%), vacA m1 (29.2%), and cagA(-) (all P < 0.05). The vacA s1m2cagA (+)
      genotype was the most prevalent within the three disease groups. vacA s1m2
      frequency was 56.2% with a similar occurrence in all diagnoses, while vacA s1m1
      appeared more often in DU patients (33.9%). A genotype of vacA s2m2 occurred in
      15% of isolates and was more common in CG patients (21.2%); vacA s2m1 was the
      least common genotype (3%). The vacA s1 allele was found to be a risk factor for
      DU, vacA s2 for CG, and vacA s1 and vacA s2 for GU (all P < 0.05). The vacA s2m2
      genotype was associated with the development of CG and GU compared to DU (P <
      0.05). No correlation was found between vacA m or cagA and gastric diseases.
      CONCLUSION: The outcome of H. pylori infection is the result of interaction
      between bacterial genotypes and the age and sex of infected individuals.

PMID- 26309358
TI  - Influence of the hTERT rs2736100 polymorphism on telomere length in gastric
      cancer.
AB  - AIM: To investigate the functional consequences of rs2736100 polymorphism in
      telomere length and examine its link to gastric cancer risk. METHODS: Telomere
      length and human telomerase reverse transcriptase (hTERT) mRNA expression were
      measured in 35 gastric cancer tissues and 5 cell lines and correlated to
      rs2736100 polymorphism. The relationship between rs2736100 polymorphism and the
      risk of gastric cancer were examined in 243 gastric cancer patients and 246
      healthy individuals. RESULTS: The rs2736100 A allele carrier is closely
      associated with reduced hTERT mRNA expression and shortened telomere length in
      gastric cancer tissue and cell lines. When gastric cancers were stratified by
      histological subtype, telomere length and hTERT mRNA levels were significantly
      increased in those with the C/C genotype in intestinal-type gastric cancer, but
      not in diffuse-type gastric cancer. Interestingly, there was no significant
      difference in the genotype and allele frequencies of the rs2736100 polymorphism
      between the patients with gastric cancer and healthy controls. CONCLUSION: The
      rs2736100 polymorphism of the hTERT gene is involved in the regulation of hTERT
      expression and telomere length, but not in the risk of gastric cancer.

PMID- 26309359
TI  - MiR-30b suppresses tumor migration and invasion by targeting EIF5A2 in gastric
      cancer.
AB  - AIM: To elucidate the potential biological role of miR-30b in gastric cancer and
      investigate the underlying molecular mechanisms of miR-30b to inhibit metastasis
      of gastric cancer cells. METHODS: The expression of miR-30b was detected in
      gastric cancer cell lines and samples by reverse transcription-polymerase chain
      reaction. CCK-8 assays were conducted to explore the impact of miR-30b
      overexpression on the proliferation of gastric cancer cells. Flow cytometry was
      used to examine the effect of miR-30b on the apoptosis. Transwell test was used
      for the migration and invasion assays. Luciferase reporter assays and Western
      blot were employed to validate regulation of putative target of miR-30b. RESULTS:
      The results showed that miR-30b was downregulated in gastric cancer tissues and
      cancer cell lines and functioned as a tumor suppressor. Overexpression of miR-30b
      promoted cell apoptosis, and suppressed proliferation, migration and invasion of
      the gastric cancer cell lines AGS and MGC803. Bioinformatic analysis identified
      the 3'-untranslated region of eukaryotic translation initiation factor 5A2
      (EIF5A2) as a putative binding site of miR-30b. Luciferase reporter assays and
      Western blot analysis confirmed the EIF5A2 gene as a target of miR-30b. Moreover,
      expression levels of the EIF5A2 targets E-cadherin and Vimentin were altered
      following transfection of miR-30b mimics. CONCLUSION: Our findings describe a
      link between miR-30b and EIF5A2, which plays an important role in mediating
      epithelial-mesenchymal transition.

PMID- 26309361
TI  - Mechanism of aqueous fructus aurantii immaturus extracts in neuroplexus of
      cathartic colons.
AB  - AIM: To examine the effect of aqueous fructus aurantii immaturus (FAI) extracts
      on the intestinal plexus of cathartic colons. METHODS: Cathartic colons were
      induced in rats with dahuang, a laxative used in traditional Chinese medicine.
      Once the model was established (after approximately 12 wk), rats were
      administered mosapride (1.54 mg/kg) or various doses of aqueous FAI extracts (1-4
      g/kg) for 14 d. Transit function was assessed using an ink propulsion test. Rats
      were then sacrificed, and the ultramicrostructure of colonic tissue was examined
      using transmission electron microscopy. The expression of the 5-hydroxytryptamine
      receptor 4 (5-HTR4) and neurofilament-H was assessed in colon tissues using real
      time PCR, Western blot, and immunohistochemistry. RESULTS: Mosapride and high
      dose (4 g/kg) of aqueous FAI extracts significantly improved the bowel movement
      in cathartic colons compared to untreated model colons as measured by the
      intestinal transit rate (70.06 +/- 7.25 and 72.02 +/- 8.74, respectively, vs
      64.12 +/- 5.19; P < 0.05 for both). Compared to controls, the ultramicrostructure
      of cathartic colons showed signs of neural degeneration. Treatment with mosapride
      and aqueous FAI extracts resulted in recovery of ultrastructural pathology.
      Treatment with mosapride alone upregulated the gene and protein expression of 5
      HTR4 compared to untreated controls (P < 0.05 for both). Treatment with aqueous
      FAI extracts (>= 2 g/kg) increased 5-HTR4 mRNA levels (P < 0.05), but no change
      in protein level was observed by Western blot or immunohistochemistry. The mRNA
      and protein levels of neurofilament-H were significantly increased with mosapride
      and >= 2 g/kg aqueous FAI extracts compared to controls (P < 0.05 for all).
      CONCLUSION: Aqueous FAI extracts and mosapride strengthen bowel movement in
      cathartic colons via increasing the expression of 5-HTR4 and neurofilament-H.

PMID- 26309360
TI  - Linc00675 is a novel marker of short survival and recurrence in patients with
      pancreatic ductal adenocarcinoma.
AB  - AIM: To detect linc00675 expression in pancreatic ductal adenocarcinoma (PDAC),
      to analyze the relationship between the expression level of linc00675 and the
      clinical pathological characteristics, to explore the biological functions of
      linc00675, and to determine whether linc00675 has independent prognostic value in
      PDAC. METHODS: We studied linc00675 expression among eight histologically
      confirmed PDAC tissue samples and four chronic pancreatitis tissue samples
      through microarray screening. RT-qPCR was conducted to further investigate
      linc00675 expression in PDAC cell lines as well as archived tissues from a large
      cohort of PDAC patients. The correlations between the level of lnc00675 and
      clinicopathological characteristics and survival in patients with pancreatic
      cancer were evaluated using Correlation analysis. Univariate and multivariate
      analyses were conducted to predict whether lnc00675 expression is an independent
      prognostic and recurrence factor in patients with pancreatic cancer. After
      downregulating the expression of linc00675 through siRNA, MTT assay, flow
      cytometry, transwell assay and Western blot were used to explore the biological
      function of linc00675 in proliferation, invasion, and cell cycle progression of
      pancreatic cancer cells. The relative molecular expression levels of epithelial
      mesenchymal transition were determined by reverse transcription-polymerase chain
      reaction (RT-PCR) and Western blot. RESULTS: The expression of Linc00675 in PDAC
      tissue samples was shown to be 672 times that in chronic pancreatitis tissue
      samples by microarray screening (P = 3.69 * 10(-5)). This finding was confirmed
      in tumor tissues from 90 patients with PDAC compared with adjacent normal tissue
      samples by quantitative RT-PCR. We found that linc00675 overexpression positively
      correlated with lymph node metastasis (P = 0.005), perineural invasion (P =
      0.006), and poor survival (P < 0.001). Univariate and multivariate analyses
      showed that linc00675 expression served as an independent predictor of overall
      survival (P = 0.009). Additionally, receiver operating characteristic curve
      analysis showed that high linc00675 might serve as a predictor of tumor
      progression within 6 mo to a year after surgery. In vitro functional analysis
      demonstrated that knockdown of linc00675 attenuated pancreatic cancer cell
      proliferation and invasion as well as induced S phase arrest. Suppression of
      linc00675 in pancreatic cancer cells resulted can reverse the progress of
      epithelial-mesenchymal transition. CONCLUSION: Linc00675 may function as an
      oncogene during PDAC development, and its expression is an independent predictor
      of unfavorable prognosis in patients with PDAC.

PMID- 26309362
TI  - Fluid resuscitation in acute pancreatitis: Normal saline or lactated Ringer's
      solution?
AB  - AIM: To investigate whether administration of Ringer's solution (RL) could have
      an impact on the outcome of acute pancreatitis (AP). METHODS: We conducted a
      retrospective study on 103 patients [68 men and 35 women, mean age 51.2 years
      (range, 19-92 years)] hospitalized between 2011 and 2012. All patients admitted
      to the Department of Gastroenterology of the Central Clinical Hospital of the
      Ministry of Interior (Poland) with a diagnosis of AP who had disease onset within
      48 h of presentation were included in this study. Based on the presence of
      persistent organ failure (longer than 48 h) as a criterion for the diagnosis of
      severe AP (SAP) and the presence of local complications [diagnosis of moderately
      severe AP (MSAP)], patients were classified into 3 groups: mild AP (MAP), MSAP
      and SAP. Data were compared between the groups in terms of severity (using the
      revised Atlanta criteria) and outcome. Patients were stratified into 2 groups
      based on the type of fluid resuscitation: the 1-RL group who underwent standard
      fluid resuscitation with a RL 1000 mL solution or the 2-NS group who underwent
      standard fluid resuscitation with 1000 mL normal saline (NS). All patients from
      both groups received an additional 5% glucose solution (1000-1500 mL) and a multi
      electrolyte solution (500-1000 mL). RESULTS: We observed 64 (62.1%) patients with
      MAP, 26 (25.24%) patients with MSAP and 13 (12.62%) patients with SAP. No
      significant difference in the distribution of AP severity between the two groups
      was found. In the 1-RL group, we identified 22 (55.5%) MAP, 10 (25.5%) MSAP and 8
      (20.0%) SAP patients, compared with 42 (66.7%) MAP, 16 (24.4%) MSAP and 5 (7.9%)
      SAP cases in the 2-NS group (P = 0.187). The volumes of fluid administered during
      the initial 72-h period of hospitalization were similar among the patients from
      both the 1-RL and 2-NS groups (mean 3400 mL vs 3000 mL, respectively). No
      significant differences between the 1-RL and 2-NS groups were found in confirmed
      pancreatic necrosis [10 patients (25%) vs 12 patients (19%), respectively, P =
      0.637]. There were no statistically significant differences between the 1-RL and
      2-NS groups in the percentage of patients who required enteral nutrition (23
      patients vs 17 patients, respectively, P = 0.534). Logistic regression analysis
      confirmed these findings (OR = 1.344, 95%CI: 0.595-3.035, P = 0.477). There were
      no significant differences between the 1-RL and 2-NS groups in mortality and the
      duration of hospital stay (median of 9 d for both groups, P = 0.776). CONCLUSION:
      Our study failed to find any evidence that the administration of RL in the first
      days of AP leads to improved clinical outcomes.

PMID- 26309363
TI  - Colorectal stenting for palliation and as a bridge to surgery: A 5-year follow-up
      study.
AB  - AIM: To evaluate the long-term effectiveness of colonic stents in colorectal
      tumors causing large bowel obstruction. METHODS: We retrospectively analyzed data
      from 49 patients with colorectal cancer who had undergone colorectal stent
      placement between January 2008 and January 2013. Patients' symptoms,
      characteristics and clinicopathological data were obtained by reviewing medical
      records. The obstruction was diagnosed clinically and radiologically.
      Histopathological diagnosis was achieved endoscopically. Technical success rate
      (TSR) was defined as the ratio of patients with correctly placed SEMS upon stent
      deployment across the entire stricture length to total number of patients.
      Clinical success rate (CSR) was defined as the ratio of patients with technical
      success and successful maintenance of stent function before elective surgery
      (regardless of number of SEMS deployed) to total number of patients. The surgical
      success rate (SSR) of colorectal stent as a bridge to surgery was defined as the
      ratio of patients with successful surgical procedures. Unsuccessful surgical
      outcomes were defined as being due to insufficient colonic decompression. The
      technical, clinical, surgical success rates and complications after stenting were
      assessed. RESULTS: The median age of patients was 64 (36 to 89). 44.9% of
      patients were male and 55.1% were female. Eighteen patients had the obstruction
      located in the rectum, 15 patients in the rectosigmoid region, 10 patients in the
      sigmoid region, and 6 patients had a tumor causing obstruction in the proximal
      colon. Each patient was categorized pathologically as stage 2 (32.7%, 16
      patients) or stage 3 (42.9%, 21 patients) and 12 patients (24.4%) had metastatic
      disease. None of the patients received chemotherapy before stenting. Stenting was
      undertaken in 37 patients as a bridge to surgery, and in 12 patients stents were
      used for palliation. Median time to surgery after stenting was 30 +/- 91.9 d. All
      surgery was completed in one single operation and thus no colostomy with stoma
      was needed. The median overall survival rate of patients with stage 2-3
      colorectal cancer was 53.1 mo and stage 4 was 37.1 mo (P = 0.04). Metastatic
      colorectal patients who were treated palliatively with stents had backbone
      chemotherapy with oxaliplatin and/or irinotecan-based regimens plus
      antiangiogenic therapies, especially bevacizumab. Resolution of the obstruction
      and clinical improvement was achieved in all patients. The technical, clinical
      and surgical success rates were 95.9%, 100% and 94.6%, respectively. CONCLUSION:
      The efficacy and safety of colonic stents was demonstrated both as a bridge to
      surgery and for palliative decompression. In addition, results emphasize the
      importance of the skills of the endoscopist in colonic stenting.

PMID- 26309364
TI  - Simple colonoscopy reporting system checking the detection rate of colon polyps.
AB  - AIM: To present a simple colonoscopy reporting system that can be checked easily
      the detection rate of colon polyps. METHODS: A simple colonoscopy reporting
      system Kosin Gastroenterology (KG quality reporting system) was developed. The
      polyp detection rate (PDR), adenoma detection rate (ADR), serrated polyp
      detection rate (SDR), and advanced adenoma detection rate (AADR) are easily
      calculated to use this system. RESULTS: In our gastroenterology center, the PDR,
      ADR, SDR, and AADR test results from each gastroenterologist were updated, every
      month. Between June 2014, when the program was started, and December 2014, the
      overall PDR and ADR in our center were 62.5% and 41.4%, respectively. And the
      overall SDR and AADR were 7.5% and 12.1%, respectively. CONCLUSION: We envision
      that KG quality reporting system can be applied to develop a comprehensive system
      to check colon polyp detection rates in other gastroenterology centers.

PMID- 26309365
TI  - Advantage of endoscopic mucosal resection with a cap for rectal neuroendocrine
      tumors.
AB  - AIM: To compare the outcomes of endoscopic mucosal resection with a cap (EMR-C)
      with those of endoscopic submucosal dissection (ESD) for the resection of rectal
      neuroendocrine tumors. METHODS: One hundred and sixteen lesions in 114 patients
      with rectal neuroendocrine tumor (NET) resected with EMR-C or ESD were included
      in the study. This study was performed at Pusan National University Yangsan
      Hospital between July 2009 and August 2014. We analyzed endoscopic complete
      resection rate, pathologic complete resection rate, procedure time, and adverse
      events in the EMR-C (n = 65) and ESD (n = 51) groups. We also performed a
      subgroup analysis by tumor size. RESULTS: Mean tumor size was 4.62 +/- 1.66 mm in
      the EMR-C group and 7.73 +/- 3.14 mm in the ESD group (P < 0.001). Endoscopic
      complete resection rate was 100% in both groups. Histologic complete resection
      rate was significantly greater in the EMR-C group (92.3%) than in the ESD group
      (78.4%) (P = 0.042). Mean procedure time was significantly longer in the ESD
      group (14.43 +/- 7.26 min) than in the EMR-C group (3.83 +/- 1.17 min) (P <
      0.001). Rates of histologic complete resection without complication were similar
      for tumor diameter <= 5 mm (EMR-C, 96%; ESD, 100%, P = 0.472) as well as in cases
      of 5 mm < tumor diameter <= 10 mm (EMR-C, 80%; ESD, 71.0%, P = 0.524).
      CONCLUSION: EMR-C may be simple, faster, and more effective than ESD in removing
      rectal NETs and may be preferable for resection of small rectal NETs.

PMID- 26309366
TI  - Safety validation of decision trees for hepatocellular carcinoma.
AB  - AIM: To evaluate a different decision tree for safe liver resection and verify
      its efficiency. METHODS: A total of 2457 patients underwent hepatic resection
      between January 2004 and December 2010 at the Chinese PLA General Hospital, and
      634 hepatocellular carcinoma (HCC) patients were eligible for the final analyses.
      Post-hepatectomy liver failure (PHLF) was identified by the association of
      prothrombin time < 50% and serum bilirubin > 50 MUmol/L (the "50-50" criteria),
      which were assessed at day 5 postoperatively or later. The Swiss-Clavien decision
      tree, Tokyo University-Makuuchi decision tree, and Chinese consensus decision
      tree were adopted to divide patients into two groups based on those decision
      trees in sequence, and the PHLF rates were recorded. RESULTS: The overall
      mortality and PHLF rate were 0.16% and 3.0%. A total of 19 patients experienced
      PHLF. The numbers of patients to whom the Swiss-Clavien, Tokyo University
      Makuuchi, and Chinese consensus decision trees were applied were 581, 573, and
      622, and the PHLF rates were 2.75%, 2.62%, and 2.73%, respectively. Significantly
      more cases satisfied the Chinese consensus decision tree than the Swiss-Clavien
      decision tree and Tokyo University-Makuuchi decision tree (P < 0.01,P < 0.01);
      nevertheless, the latter two shared no difference (P = 0.147). The PHLF rate
      exhibited no significant difference with respect to the three decision trees.
      CONCLUSION: The Chinese consensus decision tree expands the indications for
      hepatic resection for HCC patients and does not increase the PHLF rate compared
      to the Swiss-Clavien and Tokyo University-Makuuchi decision trees. It would be a
      safe and effective algorithm for hepatectomy in patients with hepatocellular
      carcinoma.

PMID- 26309367
TI  - High expression of CD11c indicates favorable prognosis in patients with gastric
      cancer.
AB  - AIM: To determine the relationship between CD11c expression level and prognosis
      in patients with gastric cancer (GC). METHODS: This retrospective survival study
      was performed from July 31, 2008 to June 30, 2014. Our study inclusion criteria
      included all the patients with GC who underwent surgical resection between
      January 1998 and December 2009 in the Third Affiliated Hospital of Soochow
      University. CD11c expression levels in 140 patients with GC at different UICC
      stages were evaluated using immunohistochemistry, and GC tissues from 16 cases
      were further verified by qRT-PCR. The chi (2) test was used to compare the
      patient- and disease-related factors between the low CD11c expression group and
      the high expression group. Univariate probabilities of overall survival (OS) and
      disease-free survival (DFS) were assessed using the Kaplan-Meier method. The log
      rank test was used to compare survival curves. Different multivariate COX models
      were used to estimate the association between CD11c expression and both death and
      recurrence risk in GC patients. RESULTS: The average CD11c expression level was
      5.1 +/- 1.8/high power field (HPF) in 10 gastritis samples, 4.5 +/- 2.3/HPF in 10
      gastric polyp samples and 9.7 +/- 6.3/HPF in 140 gastric cancer samples,
      respectively. The CD11c expression level was significantly decreased from UICC
      stage I to stage IV (stage I: 16.0 +/- 7.4, stage II: 10.4 +/- 5.5, stage III:
      9.4 +/- 6.1, stage IV: 5.3 +/- 3.2, P < 0.001). Patients in the high CD11c
      expression group had a greater 3- and 5-year OS probability and longer median
      survival time compared with the low CD11c expression group, (67.7% vs 39.2%;
      51.4% vs 29.0%; 67.0 mo vs 28.0 mo; chi(2) = 6.80, P = 0.009), and had a greater
      3- and 5-year DFS probability and longer median DFS time (63.7% vs 24.0%; 49.1%
      vs 11.9%; 64.0 mo vs 18.0 mo; chi (2) = 15.39, P < 0.001). Patients with high
      CD11c high expression had a reduced risk of death (HR = 0.56, 95%CI: 0.33-0.98, P
      < 0.05) and relapse (HR = 0.39, 95%CI: 0.23-0.67, P < 0.01) compared with
      patients with low CD11c expression after adjustment of potential confounders,
      with the exception of tumor size. However, the protective effect related to death
      (HR = 0.90, 95%CI: 0.49-1.67, P = 0.749) and relapse (HR = 0.65, 95%CI: 0.36
      1.19, P = 0.160) disappeared when tumor size was incorporated into the model.
      CONCLUSION: High expression of CD11c decreased the risk of death and relapse, and
      may be regarded as an alternative indicator of favorable prognosis in patients
      with GC.

PMID- 26309368
TI  - Presence of c.3956delC mutation in familial adenomatous polyposis patients from
      Brazil.
AB  - AIM: To characterize APC gene mutations and correlate them with patient
      phenotypes in individuals diagnosed with familial adenomatous polyposis (FAP) in
      northern Brazil. METHODS: A total of 15 individuals diagnosed with FAP from 5
      different families from the north of Brazil were analyzed in this study. In
      addition to patients with histopathological diagnosis of FAP, family members who
      had not developed the disease were also tested in order to identify mutations and
      for possible genetic counseling. All analyzed patients or their guardians signed
      a consent form approved by the Research Ethics Committee of the Joao de Barros
      Barreto University Hospital (Belem, Brazil). DNA extracted from the peripheral
      blood of a member of each of the affected families was subjected to direct
      sequencing. The proband of each family was sequenced to identify germline
      mutations using the Ion Torrent platform. To validate the detected mutations,
      Sanger sequencing was also performed. The samples from all patients were also
      tested for the identification of mutations by real-time quantitative polymerase
      chain reaction using the amplification refractory mutation system. RESULTS:
      Through interviews with relatives and a search of medical records, it was
      possible to construct genograms for three of the five families included in the
      study. All 15 patients from the five families with FAP exhibited mutations in the
      APC gene, and all mutations were detected in exon 15 of the APC gene. In addition
      to the patients with a histological diagnosis of FAP, family members without
      disease symptoms showed the mutation in the APC gene. In the present study, we
      detected two of the three most frequent germline mutations in the literature: the
      mutation at codon 1309 and the mutation at codon 1061. The presence of c.3956delC
      mutation was found in all families from this study, and suggests that this
      mutation was introduced in the population of the State of Para through ancestor
      immigration (i.e., a de novo mutation that arose in one member belonging to this
      state from Brazil). CONCLUSION: Regardless of its origin, the c.3956delC mutation
      is a strong candidate biomarker of this hereditary cancer syndrome in families of
      northern Brazil.

PMID- 26309369
TI  - Robotic radiosurgery in pancreatic cancer: A systematic review.
AB  - AIM: To present a systematic review of techniques and clinical results. METHODS:
      A systematic review of published literature was performed. Only studies reporting
      patient outcome after radiosurgery (single fraction) delivered with robotic
      devices [i.e., robotic radiosurgery (RRS)] have been analyzed. RESULTS: A total
      of 96 patients from 5 studies were included. The studies are characterized by
      small series and different methods in terms of dose, target definition,
      combination with chemotherapy and/or standard fractionated radiotherapy and
      evaluation modalities. Preliminary results are positive in terms of tumor
      response (ORR = 56%) and local control of the tumor (crude rate of local
      progressions: 19.5%). Results for median overall survival (11.4 mo) seem
      comparable with the ones of prolonged chemoradiation (range: 8.6-13.0 mo).
      However, gastrointestinal toxicity seems to be the main limitation of RRS,
      especially at the duodenal level. CONCLUSION: RRS allows for local treatment in a
      shortened time (1 fraction) compared to traditional treatments (about 1 mo),
      providing the possibility for an easy integration with systemic therapies.
      Preliminary results did not show any outcome differences compared to standard
      chemoradiation. Thus, further efforts to reduce gastrointestinal toxicity are
      strongly needed.

PMID- 26309370
TI  - Helicobacter pylori and gastric mucin expression: A systematic review and meta
      analysis.
AB  - AIM: To investigate the relationship between Helicobacter pylori (H. pylori) and
      mucin expression in gastric mucosa. METHODS: English Medical literature searches
      were conducted for gastric mucin expression in H. pylori infected people vs
      uninfected people. Searches were performed up to December 31(th) 2014, using
      MEDLINE, PubMed, EMBASE, Scopus, and CENTRAL. Studies comparing mucin expression
      in the gastric mucosa in patients positive and negative for H. pylori infection,
      were included. Meta-analysis was performed by using Comprehensive meta-analysis
      software (Version 3, Biostat Inc., Englewood, NJ, United States). Pooled odds
      ratios (ORs) and 95% confidence intervals (CIs) were calculated compared mucin
      expression in individual studies by using the random effects model. Heterogeneity
      between studies was evaluated using the Cochran Q-test, and it was considered to
      be present if the Q-test P value was less than 0.10. I(2) statistic was used to
      measure the proportion of inconsistency in individual studies, with I(2) > 50%
      representing substantial heterogeneity. We also calculated a potential
      publication bias. RESULTS: Eleven studies, which represent 53 sub-studies of 15
      different kinds of mucin expression, were selected according to the inclusion
      criteria. Every kind of mucin has been considered as one study. When a specific
      mucin has been studied in more than one paper, we combined the results in a
      nested meta-analysis of this particular mucin: MUC2, MUC6, STn, Paradoxical con
      A, Tn, T, Type 1 chain mucin, LeA, SLeA, LeB, AB-PAS, MUC1, and MUC5AC. The odds
      ratio of mucin expression in random analysis was 2.33, 95%CI: 1.230-4.411, P =
      0.009, higher expression in H. pylori infected patients. Odds ratio for mucin
      expression in H. pylori positive patients was higher for MUC6 (9.244, 95%CI:
      1.567-54.515, P = 0.014), and significantly lower for MUC5AC (0.447, 95%CI: 0.211
      0.949, P = 0.036). Thus, H. pylori infection may increase MUC6 expression and
      decrease MUC5AC expression by 924% and 52%, respectively. CONCLUSION: H. pylori
      inhibits MUC5AC expression in the gastric epithelium, and facilitates
      colonization. In contrast, increased MUC6 expression may help inhibiting
      colonization, using MUC6 antibiotics properties.

PMID- 26309371
TI  - Adenocarcinoma of the third and fourth portions of the duodenum: The capsule
      endoscopy value.
AB  - Primary adenocarcinoma of the small intestine occurs in over 50% of cases in the
      duodenum. However, its location in the third and fourth duodenal portions occurs
      rarely and is a diagnostic challenge. The aim of this work is to report an
      adenocarcinoma of the third and fourth duodenal portions, emphasizing its
      diagnostic difficulty and the value of video capsule endoscopy. A man, 40 years
      old, with no medical history, with abdominal discomfort and progressive fatigue,
      presented four months ago with one episode of moderate melena. The physical
      examination was normal, except for mucosal pallor. Blood tests were consistent
      with microcytic, hypochromic iron deficiency anemia with 7.8 g/dL hemoglobin. The
      upper and lower endoscopy were normal. Additional work-up with video capsule
      endoscopy showed a polypoid lesion involving the third and fourth portions of the
      duodenum. Biopsy showed a moderately differentiated adenocarcinoma. Abdominal
      computed tomography showed a wall thickening from the third duodenal portion to
      the proximal jejunum, without distant metastasis. The patient underwent segmental
      resection (distal duodenum and proximal jejunum) with duodenojejunostomy. The
      surgical specimen histology confirmed the biopsy diagnosis, with transmural
      infiltration, without nodal involvement. CONCLUSION: Adenocarcinoma of the third
      and fourth portions of the duodenum is difficult to diagnose and capsule
      endoscopy is of great value.

PMID- 26309373
TI  - Immunoglobulin G4-related autoimmune pancreatitis and sialadenitis: A case
      report.
AB  - Immunoglobulin G4 (IgG4)-related disease is a rare systemic diseases. A 67-year
      old male presented at our institution with mild upper abdominal pain and jaundice
      for 20 d. Laboratory results revealed high levels of IgG4 (15.4 g/L, range: 0.08
      1.4 g/L). Computed tomography (CT) showed significant enlargement of the entire
      pancreas and a capsule-like low-density rim surrounding the whole pancreas.
      Positron emission tomography/CT revealed increased uneven metabolism of the
      entire pancreas. Both magnetic resonance cholangiopancreatography and endoscopic
      retrograde cholangiopancreatography showed stenosis of the distal common bile
      duct and proximal main pancreatic duct, and dilation of the proximal common bile
      duct and extra- and intra-hepatic bile ducts. He was diagnosed with IgG4-related
      autoimmune pancreatitis. The patient was treated with prednisone for 14 mo. The
      patient responded well to prednisone but upon cessation of the corticosteroid
      developed enlargement of the submandibular gland. The patient's serum IgG4 was
      elevated at 23.9 g/L. It is important to maintain treatment, so the patient was
      again treated with prednisone and had a good response. Follow-up of IgG4-related
      disease is thus necessary. 

PMID- 26309372
TI  - Pancreatic paraganglioma with draining vessels.
AB  - A pancreatic paraganglioma is a rare neoplasm that is difficult to distinguish
      from a pancreatic neuroendocrine tumour. Here we present a case of pancreatic
      paraganglioma that was surgically resected following preoperative diagnosis of a
      pancreatic neuroendocrine tumour. Careful evaluation of the endoscopic
      ultrasonography findings revealed abundant draining vessels, which could have led
      to a correct preoperative diagnosis of pancreatic paraganglioma. 

PMID- 26309375
TI  - The best is yet to come: 2015 and beyond.

PMID- 26309374
TI  - Growth hormone used to control intractable bleeding caused by radiation-induced
      gastritis.
AB  - Intractable bleeding caused by radiation-induced gastritis is rare. We describe a
      69-year-old man with intractable hemorrhagic gastritis induced by postoperative
      radiotherapy for the treatment of esophageal carcinoma. Although anti-secretory
      therapy with or without octreotide was initiated for hemostasis over three
      months, melena still occurred off and on, and the patient required blood
      transfusions to maintain stable hemoglobin. Finally growth hormone was used in
      the treatment of hemorrhage for two weeks, and hemostasis was successfully
      achieved. This is the first report that growth hormone has been used to control
      intractable bleeding caused by radiation-induced gastritis. 

PMID- 26309376
TI  - Short-term effects of thoracic spinal manipulations and message conveyed by
      clinicians to patients with musculoskeletal shoulder symptoms: a randomized
      clinical trial.
AB  - STUDY DESIGN: Randomized clinical trial. OBJECTIVES: To evaluate the effects of
      high-velocity, low-amplitude thrust manipulations (HVLATMs) and various messages
      on patients with musculoskeletal shoulder symptoms. BACKGROUND: Previous studies
      indicated that HVLATM directed at the thoracic spine and ribs resulted in
      improvements of shoulder range of motion, pain, and disability in patients with
      musculoskeletal shoulder symptoms. These studies did not explore if the outcome
      was dependent on thrust location, clinician communication with the patient, or if
      there were any lasting effects. METHODS: A consecutive sample of 100 patients
      with shoulder pain was randomized into four groups. Patients received one
      intervention session including: six thoracic HVLATM (spine versus scapula), a
      message about HVLATM (neutral versus positive), and standardized home exercises.
      Outcome measures included shoulder Numeric Pain Rating Scale (NPRS), NPRS with
      impingement testing, and Shoulder Pain and Disability Index (SPADI). Measurements
      were recorded prior to intervention, immediately following intervention, and at
      short-term follow-up. Kruskal-Wallis statistics were used for between-group
      comparisons and Wilcoxon signed ranks for within-group comparisons. RESULTS:
      Eighty-eight patients (22 per group) completed the study. Statistically
      significant differences were found for within-group comparisons for most time
      points assessed. No statistical differences were found for between-group
      comparisons. CONCLUSION: Patients improved following the interventions. Neither
      the type of HVLATM nor the message conveyed to the patients had a significant
      effect on the patients' improvements. LEVEL OF EVIDENCE: 1b.

PMID- 26309377
TI  - Validity of pain drawings for predicting psychological status outcome in patients
      with recurrent or chronic low back pain.
AB  - OBJECTIVES: To investigate the association between baseline pain drawings and
      future psychological status, and estimate the prognostic value of pain drawing
      assessment for predicting somatization, distress, and depression at one-year
      follow-up, in patients with recurrent or chronic low back pain (RCLBP). METHODS:
      This was a multi-center prospective cohort study of 138 patients with RCLBP.
      Participating patients completed at baseline and one-year follow-up: a blank pain
      drawing; the Modified Somatic Perceptions Questionnaire; modified Zung Depression
      Scale; and Distress and Risk Assessment Method. Pain drawings were analyzed
      quantitatively using the Pain Sites Score (PSS) and Simple Body Region (SBR)
      method. The association between baseline pain drawing assessment and one-year
      psychological status was estimated using correlation and Relative Risk (RR)
      statistics. RESULTS: We obtained complete data from 81 patients (59%).
      Psychological status and pain drawings did not differ significantly between
      completers and non-completers. Pain drawing area at baseline was associated with
      depression and somatization at one-year follow-up (Spearman's Rho 0.25, P =
      0.022; 0.31 P = 0.006, respectively). Stronger associations resulted from
      analyses using the PSS, compared with the SBR. Patients with abnormal PSS pain
      drawings at baseline had significantly greater RR of depression (RR 6.1, 95% CI
      1.1, 33.5), somatization (RR 4.1, 95% CI 1.7, 9.9) and distress (RR 6.8, 95% CI
      1.9, 25.3) at one-year follow-up. DISCUSSION: These results provide the first
      evidence that abnormal baseline pain drawings predict greater risk of abnormal
      psychological states or poor psychological outcome at one-year follow-up, in
      patients with RCLBP.

PMID- 26309378
TI  - Chronic sacroiliac joint and pelvic girdle dysfunction in a 35-year-old
      nulliparous woman successfully managed with multimodal and multidisciplinary
      approach.
AB  - BACKGROUND AND PURPOSE: Sacroiliac joint pain and dysfunction affect 15-25% of
      patients reporting low back pain, including reports of spontaneous, idiopathic,
      traumatic, and non-traumatic onsets. The poor reliability and validity associated
      with diagnostic clinical and imaging techniques leads to challenges in diagnosing
      and managing sacroiliac joint dysfunction. CASE DESCRIPTION: A 35-year-old
      nulliparous female with a 14-year history of right sacroiliac joint dysfunction
      was managed using a multimodal and multidisciplinary approach when symptoms
      failed to resolve after 2 months of physical therapy. The plan of care included
      four prolotherapy injections, sacroiliac joint manipulation into nutation, pelvic
      girdle belting, and specific stabilization exercises. OUTCOMES: The patient
      completed 20 physical therapy sessions over a 12-month period. At 6 months, the
      patient's Oswestry Disability Questionnaire score was reduced from 34% to 14%. At
      1-year follow-up, her score was 0%. The patient's rating of pain on a numeric
      rating scale decreased to an average of 4/10 at 6 months and 0/10 at 1-year
      follow-up. DISCUSSION: A multidisciplinary and multimodal approach for the
      management of chronic sacroiliac joint dysfunction appeared successful in a
      single-case design at 1-year follow-up.

PMID- 26309379
TI  - Establishing assessment criteria for clinical reasoning in orthopedic manual
      physical therapy: a consensus-building study.
AB  - OBJECTIVES: Clinical reasoning (CR) represents one of the core components of
      clinical competence in Orthopaedic Manual Physical Therapy (OMPT). While
      education standards have been developed to guide curricular design, assessment of
      CR has not yet been standardized. Without theory-informed and rigorously
      developed measures, the certification of OMPTs lacks credibility and is less
      defensible. The purpose of this study was to use a theory-informed approach to
      generate assessment criteria for developing new assessment tools to evaluate CR
      in OMPT. METHODS: A list of assessment criteria was generated based on
      international education standards and multiple theoretical perspectives. A
      modified Delphi method was used to gain expert consensus on the importance of
      these assessment criteria for the assessment of CR in OMPT. The OMPTs from 22
      countries with experience in assessing CR were invited to participate in three
      rounds of online questionnaires to rate their level of agreement with these
      criteria. Responses were tabulated to analyze degree of consensus and internal
      consistency. RESULTS: Representatives from almost half of the OMPT member
      organizations (MO) participated in three rounds of the Delphi. High levels of
      agreement were found among respondents regarding the importance and feasibility
      of most assessment criteria. There was high internal consistency among items
      within the proposed item subgroupings. DISCUSSION: A list of assessment criteria
      has been established that will serve as a framework for developing new assessment
      tools for CR assessment in OMPT. These criteria will be important for guiding the
      design of certification processes in OMPT as well as other episodes of CR
      assessment throughout OMPT training.

PMID- 26309380
TI  - A multimodal physical therapy approach to the management of a patient with
      temporomandibular dysfunction and head and neck lymphedema: a case report.
AB  - OBJECTIVE AND IMPORTANCE: There is a paucity of research that investigates
      therapeutic interventions of patients with concurrent head and neck lymphedema
      and temporomandibular dysfunction (TMD). The purpose of this case report is to
      describe the management and outcomes of a patient with head and neck lymphedema
      and TMD using a multimodal physical therapy approach. CLINICAL PRESENTATION: A 74
      year-old male with a past medical history of head and neck lymphedema and TMD was
      referred to physical therapy with chief complaints of inability to open his mouth
      in order to eat solid food, increased neck lymphedema, temporomadibular joint
      pain, and inability to speak for prolonged periods of time. INTERVENTIONS: The
      patient was treated for three visits over 4 weeks. Treatment included complete
      decongestive therapy (CDT), manual therapy, therapeutic exercise, and a home
      exercise program. Upon discharge, the patient had improved mandibular depression,
      decreased head and neck lymphedema, improved deep neck flexor endurance,
      decreased pain, and improved function on the Patient Specific Functional Scale
      (PSFS). CONCLUSION: Utilization of a multimodal physical therapy approach to
      treat a patient with a complex presentation yielded positive outcomes. Further
      research on outcomes and treatment approaches in patients with TMD and head and
      neck lymphedema is warranted.

PMID- 26309381
TI  - Immediate effects of upper thoracic spine manipulation on hypertensive
      individuals.
AB  - PURPOSE: The aims of this study were to determine if there were any statistically
      significant immediate effects of upper thoracic spinal manipulative therapy (SMT)
      on cardiovascular physiology in hypertensive individuals. INTRODUCTION:
      Preliminary research suggests that SMT to various regions of the spine may be
      capable of lowering systolic and diastolic blood pressure in hypertensive
      individuals. Further studies are warranted to corroborate or refute these
      findings as well as measure how other attributes of cardiovascular physiology are
      impacted by SMT. METHODS: Fifty hypertensive participants (age = 45.5+/-13.9
      years, height = 1.69+/-0.10 m, body mass = 93.9+/-21.5 kg: mean+/-standard
      deviation (SD)) were equally randomized into a single-blind, controlled trial
      involving two study groups: supine diversified anterior upper thoracic SMT of T1
      4, or a 'no T-spine contact' control. Outcome measures were electrocardiogram,
      bilateral pulse oximetry, and bilateral blood pressure measurement performed at
      baseline, post 1-minute intervention, and post 10-minute intervention. An
      independent samples t-test was used to compare between-group differences at
      baseline. A repeated measures ANOVA was used to compare within-group changes over
      time. RESULTS: Within-group changes in PR interval and QRS duration demonstrated
      that the atria were transiently less active post-SMT and the ventricles were more
      active post-SMT, however the changes were clinically minimal. CONCLUSION: The
      results of this study, and the limited existing normotensive, thoracic-specific
      SMT research in this field, suggest that cardiovascular physiology, short-term,
      is not affected by upper thoracic spine SMT in hypertensive individuals to a
      clinically relevant level.

PMID- 26309382
TI  - Imaging in conjunction with physical therapy in management of a patient with
      history of thoracic tumour.
AB  - BACKGROUND: Physical therapy care for musculoskeletal conditions includes an
      ongoing process that systematically considers and prioritises diagnostic
      hypotheses. These diagnostic hypotheses include those that are typical for common
      musculoskeletal conditions, and must also include more rare conditions that would
      require care outside the scope of practice of the physical therapist. When
      additional screening is required, physical therapists collaborate with other
      providers or directly order the appropriate tests to rule out suspected
      pathology. CASE DESCRIPTION: This article illustrates the use of musculoskeletal
      imaging ordered by a physical therapist to guide ongoing management of a patient
      with back pain and a history of cancer. OUTCOMES: The patient successfully
      returned to moderate-intensity sport activities after a course of physical
      therapy. DISCUSSION: This case provides an example of how clinical diagnostic
      reasoning combined with clinical privileges to order musculoskeletal imaging can
      facilitate diagnostic accuracy in a timely and cost-efficient manner.

PMID- 26309383
TI  - Biomechanics of the thorax - research evidence and clinical expertise.
AB  - Understanding the biomechanics of the thorax is critical for understanding its
      role in multiple conditions since the thorax is part of many integrated systems
      including the musculoskeletal, respiratory, cardiac, digestive and
      urogynecological. The thorax is also an integrated system within itself and an
      element of the whole body/person. Therefore, understanding the biomechanics of
      the thorax is fundamental to all forms of treatment for multiple conditions. The
      interpretation of movement examination findings depends on one's view of optimal
      biomechanics and the influential factors. This article will provide a synopsis of
      the current state of research evidence as well as observations from clinical
      experience pertaining to the biomechanics of the thorax in order to help
      clinicians organise this knowledge and facilitate evidence-based and informed
      management of the, often complex, patient with or without thoracic pain and
      impairment. The integrated systems model (ISM) will be introduced as a way to
      determine when the noted biomechanical findings are relevant to a patient's
      clinical presentation. 

PMID- 26309384
TI  - Regional interdependence and manual therapy directed at the thoracic spine.
AB  - Thoracic spine manipulation is commonly used by physical therapists for the
      management of patients with upper quarter pain syndromes. The theoretical
      construct for using thoracic manipulation for upper quarter conditions is a
      mainstay of a regional interdependence (RI) approach. The RI concept is likely
      much more complex and is perhaps driven by a neurophysiological response
      including those related to peripheral, spinal cord and supraspinal mechanisms.
      Recent evidence suggests that thoracic spine manipulation results in
      neurophysiological changes, which may lead to improved pain and outcomes in
      individuals with musculoskeletal disorders. The intent of this narrative review
      is to describe the research supporting the RI concept and its application to the
      treatment of individuals with neck and/or shoulder pain. Treatment utilizing both
      thrust and non-thrust thoracic manipulation has been shown to result in
      improvements in pain, range of motion and disability in patients with upper
      quarter conditions. Research has yet to determine optimal dosage, techniques or
      patient populations to which the RI approach should be applied; however, emerging
      evidence supporting a neurophysiological effect for thoracic spine manipulation
      may negate the need to fully answer this question. Certainly, there is a need for
      further research examining both the clinical efficacy and effectiveness of manual
      therapy interventions utilized in the RI model as well as the neurophysiological
      effects resulting from this intervention. 

PMID- 26309385
TI  - Dry needling for the management of thoracic spine pain.
AB  - Thoracic spine pain is as disabling as neck and low back pain without receiving
      the same level of attention in the scientific literature. Among the different
      structures that can refer pain to the thoracic spine, muscles often play a
      relevant role. Trigger points (TrPs) from neck, shoulder and spinal muscles can
      induce pain in the region of the thoracic spine. There is a lack of evidence
      reporting the presence of TrPs in the region of the thoracic spine, but clinical
      evidence suggests that TrPs can be a potential source of thoracic spine pain. The
      current paper discusses the role of TrPs in the thoracic spine and dry needling
      (DN) for the management of TrPs in the thoracic multifidi and longissimus
      thoracis. This paper also includes a brief discussion of the application of DN in
      other tissues such as tendons, ligaments and scars. 

PMID- 26309386
TI  - Safety of thrust joint manipulation in the thoracic spine: a systematic review.
AB  - BACKGROUND: There appears to be very little in the research literature on the
      safety of thrust joint manipulation (TJM) when applied to the thoracic spine.
      PURPOSE: To retrospectively analyze all available documented case reports in the
      literature describing patients who had experienced severe adverse events (AE)
      after receiving TJM to their thoracic spine. DATA SOURCES: Case reports published
      in peer reviewed journals were searched in Medline (using Ovid Technologies,
      Inc.), Science Direct, Web of Science, PEDro (Physiotherapy Evidence Database),
      Index of Chiropractic literature, AMED (Allied and Alternative Medicine
      Database), PubMed and the Cumulative Index to Nursing and Allied Health (CINHAL)
      from January 1950 to February 2015. STUDY SELECTION: Case reports were included
      if they: (1) were peer-reviewed; (2) were published between 1950 and 2015; (3)
      provided case reports or case series; and (4) had TJM as an intervention.
      Articles were excluded if: (1) the AE occurred without TJM (e.g. spontaneous);
      (2) the article was a systematic or literature review; or (3) it was written in a
      language other than English or Spanish. DATA EXTRACTION: Data extracted from each
      case report included: gender; age; who performed the TJM and why; presence of
      contraindications; the number of manipulation interventions performed; initial
      symptoms experienced after the TJM; as well as type of severe AE that resulted.
      RESULTS: Ten cases, reported in 7 case reports, were reviewed. Cases involved
      females (8) more than males (2), with mean age being 43.5 years (SD=18.73, Range
      = 17 -71). The most frequent AE reported was injury (mechanical or vascular) to
      the spinal cord (7/10), with pneumothorax and hematothorax (2/10) and CSF leak
      secondary to dural sleeve injury (1/10). LIMITATIONS: There were only a small
      number of case reports published in the literature and there may have been
      discrepancies between what was reported and what actually occurred, since
      physicians dealing with the effects of the AE, rather than the clinician
      performing the TJM, published the cases. CONCLUSIONS: Serious AE do occur in the
      thoracic spine, most commonly, trauma to the spinal cord, followed by
      pneumothorax. This suggests that excessive peak forces may have been applied to
      thoracic spine, and it should serve as a cautionary note for clinicians to
      decrease these peak forces.

PMID- 26309387
TI  - How Many Genes are Needed to Resolve Phylogenetic Incongruence?
AB  - The question how many genes are needed to resolve phylogenetic incongruence has
      been investigated at various taxonomic levels, yet few studies have investigated
      the minimum required numbers of selected genes based on single-gene tree
      performance at the genus level or lower. We conducted resampling analyses by
      compiling transcriptome-based single-copy nuclear gene sequences of 11 species of
      Primulina (Gesneriaceae) to investigate the minimum numbers of both random and
      selected genes needed to resolve the phylogeny. Only 8 of the 26 selected genes
      were sufficient for full resolution, while 175 genes were needed if all 830
      random genes were used. Our results provided a baseline for future sampling
      strategies of gene numbers in molecular phylogenetic studies of speciose taxa.
      The gene selection strategies based on single-gene tree performance are strongly
      recommended in phylogenic analyses. 

PMID- 26309388
TI  - Genome-wide Identification of WRKY Genes in the Desert Poplar Populus euphratica
      and Adaptive Evolution of the Genes in Response to Salt Stress.
AB  - WRKY transcription factors play important roles in plant development and
      responses to various stresses in plants. However, little is known about the
      evolution of the WRKY genes in the desert poplar species Populus euphratica,
      which is highly tolerant of salt stress. In this study, we identified 107 PeWRKY
      genes from the P. euphratica genome and examined their evolutionary relationships
      with the WRKY genes of the salt-sensitive congener Populus trichocarpa. Ten
      PeWRKY genes are specific to P. euphratica, and five of these showed altered
      expression under salt stress. Furthermore, we found that two pairs of orthologs
      between the two species showed evidence of positive evolution, with dN/dS
      ratios>1 (nonsynonymous/synonymous substitutions), and both of them altered their
      expression in response to salinity stress. These findings suggested that both the
      development of new genes and positive evolution in some orthologs of the WRKY
      gene family may have played an important role in the acquisition of high salt
      tolerance by P. euphratica. 

PMID- 26309389
TI  - Medical Image Retrieval: A Multimodal Approach.
AB  - Medical imaging is becoming a vital component of war on cancer. Tremendous
      amounts of medical image data are captured and recorded in a digital format
      during cancer care and cancer research. Facing such an unprecedented volume of
      image data with heterogeneous image modalities, it is necessary to develop
      effective and efficient content-based medical image retrieval systems for cancer
      clinical practice and research. While substantial progress has been made in
      different areas of content-based image retrieval (CBIR) research, direct
      applications of existing CBIR techniques to the medical images produced
      unsatisfactory results, because of the unique characteristics of medical images.
      In this paper, we develop a new multimodal medical image retrieval approach based
      on the recent advances in the statistical graphic model and deep learning.
      Specifically, we first investigate a new extended probabilistic Latent Semantic
      Analysis model to integrate the visual and textual information from medical
      images to bridge the semantic gap. We then develop a new deep Boltzmann machine
      based multimodal learning model to learn the joint density model from multimodal
      information in order to derive the missing modality. Experimental results with
      large volume of real-world medical images have shown that our new approach is a
      promising solution for the next-generation medical imaging indexing and retrieval
      system. 

PMID- 26309390
TI  - In Silico Neuro-Oncology: Brownian Motion-Based Mathematical Treatment as a
      Potential Platform for Modeling the Infiltration of Glioma Cells into Normal
      Brain Tissue.
AB  - Intensive glioma tumor infiltration into the surrounding normal brain tissues is
      one of the most critical causes of glioma treatment failure. To quantitatively
      understand and mathematically simulate this phenomenon, several diffusion-based
      mathematical models have appeared in the literature. The majority of them ignore
      the anisotropic character of diffusion of glioma cells since availability of
      pertinent truly exploitable tomographic imaging data is limited. Aiming at
      enriching the anisotropy-enhanced glioma model weaponry so as to increase the
      potential of exploiting available tomographic imaging data, we propose a Brownian
      motion-based mathematical analysis that could serve as the basis for a simulation
      model estimating the infiltration of glioblastoma cells into the surrounding
      brain tissue. The analysis is based on clinical observations and exploits
      diffusion tensor imaging (DTI) data. Numerical simulations and suggestions for
      further elaboration are provided. 

PMID- 26309391
TI  - Analysis of Lung Flute-collected Sputum for Lung Cancer Diagnosis.
AB  - Molecular analysis of sputum can help diagnose lung cancer. We have demonstrated
      that Lung Flute can be used to collect sputum from individuals who cannot
      spontaneously expectorate sputum. The objective of this study is to further
      evaluate the performance of the Lung Flute by comparing the characteristics of
      parallel samples collected with and without the Lung Flute and the usefulness for
      diagnosis of lung cancer. Fifty-six early-stage lung cancer patients (40 current
      smokers and 16 former smokers) and 73 cancer-free individuals (52 current smokers
      and 21 former smokers) were instructed to spontaneously cough and use Lung Flute
      for sputum sampling. Sputum cytology and polymerase chain reaction analysis of
      three miRNAs (miRs-21, 31, and 210) were performed in the specimens. All 92
      current smokers and 11 (28.7%) of 37 former smokers spontaneously expectorated
      sputum and also produced sputum when using the Lung Flute. Twenty-seven former
      smokers (70.3%) who could not spontaneously expectorate sputum, however, were
      able to produce sputum when using the Lung Flute. The specimens were of low
      respiratory origin without contamination from other sources, eg, saliva. There
      was no difference of sputum volume and cell populations, diagnostic efficiency of
      cytology, and analysis of the miRNAs in the specimens collected by the two
      approaches. Analysis of the sputum miRNAs produced 83.93% sensitivity and 87.67%
      specificity for identifying lung cancer. Therefore, sputum collected by the Lung
      Flute has comparable features as spontaneously expectorated sputum. Using the
      Lung Flute enables former smokers who cannot spontaneously expectorate to provide
      adequate sputum to improve sputum collection for lung cancer diagnosis. 

PMID- 26309392
TI  - Class III Receptor Tyrosine Kinases in Acute Leukemia - Biological Functions and
      Modern Laboratory Analysis.
AB  - Acute myeloid leukemia (AML) is a complex disease caused by deregulation of
      multiple signaling pathways. Mutations in class III receptor tyrosine kinases
      (RTKs) have been implicated in alteration of cell signals concerning the growth
      and differentiation of leukemic cells. Point mutations, insertions, or deletions
      of RTKs as well as chromosomal translocations induce constitutive activation of
      the receptor, leading to uncontrolled proliferation of undifferentiated myeloid
      blasts. Aberrations can occur in all domains of RTKs causing either the ligand
      independent activation or mimicking the activated conformation. The World Health
      Organization recommended including RTK mutations in the AML classification since
      their detection in routine laboratory diagnostics is a major factor for
      prognostic stratification of patients. Polymerase chain reaction (PCR)-based
      methods are well-validated for the detection of fms-related tyrosine kinase 3
      (FLT3) mutations and can easily be applied for other RTKs. However, when
      methodological limitations are reached, accessory techniques can be applied. For
      a higher resolution and more quantitative approach compared to agarose gel
      electrophoresis, PCR fragments can be separated by capillary electrophoresis.
      Furthermore, high-resolution melting and denaturing high-pressure liquid
      chromatography are reliable presequencing screening methods that reduce the
      sample amount for Sanger sequencing. Because traditional DNA sequencing is time
      consuming, next-generation sequencing (NGS) is an innovative modern possibility
      to analyze a high amount of samples simultaneously in a short period of time. At
      present, standardized procedures for NGS are not established, but when this
      barrier is resolved, it will provide a new platform for rapid and reliable
      laboratory diagnostic of RTK mutations in patients with AML. In this article, the
      biological and physiological role of RTK mutations in AML as well as possible
      laboratory methods for their detection will be reviewed. 

PMID- 26309393
TI  - Effects of High Fat Feeding on Adipose Tissue Gene Expression in Diabetic Goto
      Kakizaki Rats.
AB  - Development and progression of type 2 diabetes is a complex interaction between
      genetics and environmental influences. High dietary fat is one environmental
      factor that is conducive to the development of insulin-resistant diabetes. In the
      present report, we compare the responses of lean poly-genic, diabetic Goto
      Kakizaki (GK) rats to those of control Wistar-Kyoto (WKY) rats fed a high fat
      diet from weaning to 20 weeks of age. This comparison included a wide array of
      physiological measurements along with gene expression profiling of abdominal
      adipose tissue using Affymetrix gene array chips. Animals of both strains fed a
      high fat diet or a normal diet were sacrificed at 4, 8, 12, 16, and 20 weeks for
      this comparison. The microarray analysis revealed that the two strains developed
      different adaptations to increased dietary fat. WKY rats decrease fatty acid
      synthesis and lipogenic processes whereas GK rats increase lipid elimination.
      However, on both diets the major differences between the two strains remained
      essentially the same. Specifically relative to the WKY strain, the GK strain
      showed lipoatrophy, chronic inflammation, and insulin resistance. 

PMID- 26309394
TI  - 20(S)-ginsenoside Rg3 promotes senescence and apoptosis in gallbladder cancer
      cells via the p53 pathway.
AB  - Gallbladder cancer (GBC), the most frequent malignancy of the biliary tract, is
      associated with high mortality and extremely poor prognosis. 20(S)-ginsenoside
      Rg3 (20(S)-Rg3) is a steroidal saponin with high pharmacological activity.
      However, the anticancer effect of 20(S)-Rg3 in human GBC has not yet been
      determined. In this study, we primarily found that 20(S)-Rg3 exposure suppressed
      the survival of both NOZ and GBC-SD cell lines in a concentration-dependent
      manner. Moreover, induction of cellular senescence and G0/G1 arrest by 20(S)-Rg3
      were accompanied by a large accumulation of p53 and p21 as a result of murine
      double minute 2 (MDM2) inhibition. 20(S)-Rg3 also caused a remarkable increase in
      apoptosis via the activation of the mitochondrial-mediated intrinsic caspase
      pathway. Furthermore, intraperitoneal injection of 20(S)-Rg3 (20 or 40 mg/kg) for
      3 weeks markedly inhibited the growth of xenografts in nude mice. Our results
      demonstrated that 20(S)-Rg3 potently inhibited growth and survival of GBC cells
      both in vitro and in vivo. 20(S)-Rg3 attenuated GBC growth probably via
      activation of the p53 pathway, and subsequent induction of cellular senescence
      and mitochondrial-dependent apoptosis. Therefore, 20(S)-Rg3 may be a potential
      chemotherapeutic agent for GBC therapy. 

PMID- 26309395
TI  - Tongguan capsule ameliorates coronary artery stenosis in a 40-year-old woman.
AB  - Cardiovascular disease is the leading cause of death worldwide, with coronary
      heart disease as the major contributor to this related mortality. There is a
      growing trend in the application of Chinese medicine in clinical practice for the
      treatment of coronary heart disease. However, there is a lack of knowledge
      surrounding the pharmacological, toxicological, and biological profiles of
      Chinese medicine. In this case report, we describe the therapeutic effects of
      Tongguan capsule in a 40-year-old woman diagnosed with stable angina pectoris. To
      the best of the authors' knowledge, this is the first case documented of the
      therapeutic effect of Tongguan capsule in the treatment of coronary heart
      disease. 

PMID- 26309396
TI  - Transarterial chemoembolization versus hepatic resection in hepatocellular
      carcinoma treatment: a meta-analysis.
AB  - BACKGROUND: A number of cohort studies have compared the outcomes of
      transarterial chemoembolization (TACE) and hepatic resection (HR) in the
      treatment of hepatocellular carcinoma (HCC). However, the effect of TACE versus
      HR remains controversial. Therefore, we conducted a meta-analysis to assess the
      effectiveness of TACE and HR in HCC treatment. MATERIALS AND METHODS: PubMed,
      Embase, Web of Science, Scopus, ClinicalTrials.gov, and Cochrane library were
      searched from their inception until February 27, 2015 for relevant studies. The
      literature search was updated on May 25, 2015. Eligible studies were cohort
      studies comparing the survival outcomes between HCC patients undergoing TACE and
      HR. The primary outcome was overall survival (OS). Secondary outcomes were the
      recurrence rate and prognostic factors for OS. The risk ratio (RR) was used for
      the meta-analysis and was expressed with 95% confidence intervals (CIs). RESULTS:
      This meta-analysis included eleven cohort studies with 6,297 patients, all
      treated with TACE or HR. Pooled estimates showed that, compared with TACE, HR
      significantly improved the 3-year OS (RR =0.77; 95% CI, 0.63-0.93; P=0.009). TACE
      and HR had similar effects on OS after 1 year (RR =0.94; 95% CI, 0.86-1.01;
      P=0.103), 2 years (RR =0.50; 95% CI, 0.21-1.19; P=0.114), 4 years (RR =0.61; 95%
      CI, 0.58-1.10; P=0.174), and 5 years (RR =0.77; 95% CI, 0.59-1.01; P=0.06). There
      was no significant difference between the 3-year (RR =1.31; 95% CI, 0.65-2.64;
      P=0.457) and 5-year recurrence rates (RR =1.14; 95% CI, 0.69-1.89; P=0.597) in
      the TACE and HR groups. Age (>65 vs <=65 years; hazard ratio =0.99; 95% CI, 0.98
      1.00; P=0.000), sex (male vs female; hazard ratio =0.79; 95% CI, 0.65-0.96;
      P=0.02), treatment method (TACE vs HR; hazard ratio =1.90; 95% CI, 1.46-2.46;
      P=0.000), and Eastern Cooperative Oncology Group performance score (>=1 vs 0;
      hazard ratio =1.69; 95% CI, 1.22-2.33; P=0.002) were independent predictors for
      OS. CONCLUSION: This meta-analysis suggests that the TACE and HR likely have
      similar effects in the treatment of HCC patients in terms of OS and recurrence
      rate. However, this conclusion should be interpreted cautiously due to the
      presence of further subgroup analyses with respect to outcomes in patients with
      different liver statuses (Barcelona Clinic Liver Cancer stage A or stage B).

PMID- 26309398
TI  - Stepwise design, synthesis, and in vitro antifungal screening of (Z)-substituted
      propenoic acid derivatives with potent broad-spectrum antifungal activity.
AB  - Fungal infections are a main reason for the high mortality rate worldwide. It is
      a challenge to design selective antifungal agents with broad-spectrum activity.
      Lanosterol 14alpha-demethylase is an attractive target in the design of
      antifungal agents. Seven compounds were selected from a number of designed
      compounds using a rational docking study. These compounds were synthesized and
      evaluated for their antifungal activity. In silico study results showed the high
      binding affinity to lanosterol 14alpha-demethylase (-24.49 and -25.83 kcal/mol)
      for compounds V and VII, respectively; these values were greater than those for
      miconazole (-18.19 kcal/mol) and fluconazole (-16.08 kcal/mol). Compound V
      emerged as the most potent antifungal agent among all compounds with a half
      maximal inhibitory concentration of 7.01, 7.59, 7.25, 31.6, and 41.6 ug/mL
      against Candida albicans, Candida parapsilosis, Aspergillus niger, Trichophyton
      rubrum, and Trichophyton mentagrophytes, respectively. The antifungal activity
      for most of the synthesized compounds was more potent than that of miconazole and
      fluconazole. 

PMID- 26309399
TI  - Navigating the chemical space of dipeptidyl peptidase-4 inhibitors.
AB  - This study represents the first large-scale study on the chemical space of
      inhibitors of dipeptidyl peptidase-4 (DPP4), which is a potential therapeutic
      protein target for the treatment of diabetes mellitus. Herein, a large set of
      2,937 compounds evaluated for their ability to inhibit DPP4 was compiled from the
      literature. Molecular descriptors were generated from the geometrically optimized
      low-energy conformers of these compounds at the semiempirical AM1 level. The
      origins of DPP4 inhibitory activity were elucidated from computed molecular
      descriptors that accounted for the unique physicochemical properties inherently
      present in the active and inactive sets of compounds as defined by their
      respective half maximal inhibitory concentration values of less than 1 MUM and
      greater than 10 MUM, respectively. Decision tree analysis revealed the importance
      of molecular weight, total energy of a molecule, topological polar surface area,
      lowest unoccupied molecular orbital, and number of hydrogen-bond donors, which
      correspond to molecular size, energy, surface polarity, electron acceptors, and
      hydrogen bond donors, respectively. The prediction model was subjected to
      rigorous independent testing via three external sets. Scaffold and chemical
      fragment analysis was also performed on these active and inactive sets of
      compounds to shed light on the distinguishing features of the functional
      moieties. Docking of representative active DPP4 inhibitors was also performed to
      unravel key interacting residues. The results of this study are anticipated to be
      useful in guiding the rational design of novel and robust DPP4 inhibitors for the
      treatment of diabetes. 

PMID- 26309400
TI  - Evaluation of trends of drug-prescribing patterns based on WHO prescribing
      indicators at outpatient departments of four hospitals in southern Ethiopia.
AB  - BACKGROUND: Rational prescribing is a primary step to ensure rational drug use.
      Often, half of the medicines are prescribed irrationally and half of these are
      even used incorrectly as the patients fail to take their medicines appropriately.
      The aim of this research was to evaluate drug-prescribing patterns of four
      hospitals in southern Ethiopia. METHODS: A retrospective cross-sectional study
      was conducted between May 15 and June 25, 2014, to evaluate the drug-prescribing
      patterns based on the World health Organization (WHO) prescribing indicators. The
      prescription papers, kept for the last 1 year in the outpatient departments of
      the four hospitals, were analyzed according to WHO guidelines. Also,
      prescriptions in the hospitals were analyzed to determine the most frequently
      prescribed drugs. All the statistical calculations were performed using SPSS((r))
      version 20.0 software. RESULTS AND DISCUSSION: The average number of drugs per
      prescription ranges from 1.82+/-0.90 to 2.28+/-0.90, whereas the percentage of
      use of antibiotics and injections ranged from 46.7 to 85 and 15 to 61.7,
      respectively. The average percentages of drugs prescribed by generic name and
      from the essential drugs list were 95.8 and 94.1, respectively. Anti-infective
      and analgesic drugs are found to be the most frequently prescribed medicines. In
      terms of polypharmacy, there was a slight deviation in prescribing patterns from
      what is acceptable according to the WHO criteria. Prescribing by generic name and
      from essential drug list was almost optimal. There was a significant deviation in
      the use of injectables in two of the four hospitals (50%), whereas their use in
      the other two hospitals was within the acceptable range. The use of antibiotics
      in all the hospitals in present study was higher than the acceptable range.
      CONCLUSION: Generally, it seems that there is need for improvement of the
      prescribing patterns in the hospitals, although this should be consolidated with
      further studies to link the patient diagnosis and the prescribed medications.

PMID- 26309397
TI  - Clinical development of galunisertib (LY2157299 monohydrate), a small molecule
      inhibitor of transforming growth factor-beta signaling pathway.
AB  - Transforming growth factor-beta (TGF-beta) signaling regulates a wide range of
      biological processes. TGF-beta plays an important role in tumorigenesis and
      contributes to the hallmarks of cancer, including tumor proliferation, invasion
      and metastasis, inflammation, angiogenesis, and escape of immune surveillance.
      There are several pharmacological approaches to block TGF-beta signaling, such as
      monoclonal antibodies, vaccines, antisense oligonucleotides, and small molecule
      inhibitors. Galunisertib (LY2157299 monohydrate) is an oral small molecule
      inhibitor of the TGF-beta receptor I kinase that specifically downregulates the
      phosphorylation of SMAD2, abrogating activation of the canonical pathway.
      Furthermore, galunisertib has antitumor activity in tumor-bearing animal models
      such as breast, colon, lung cancers, and hepatocellular carcinoma. Continuous
      long-term exposure to galunisertib caused cardiac toxicities in animals requiring
      adoption of a pharmacokinetic/pharmacodynamic-based dosing strategy to allow
      further development. The use of such a pharmacokinetic/pharmacodynamic model
      defined a therapeutic window with an appropriate safety profile that enabled the
      clinical investigation of galunisertib. These efforts resulted in an intermittent
      dosing regimen (14 days on/14 days off, on a 28-day cycle) of galunisertib for
      all ongoing trials. Galunisertib is being investigated either as monotherapy or
      in combination with standard antitumor regimens (including nivolumab) in patients
      with cancer with high unmet medical needs such as glioblastoma, pancreatic
      cancer, and hepatocellular carcinoma. The present review summarizes the past and
      current experiences with different pharmacological treatments that enabled
      galunisertib to be investigated in patients. 

PMID- 26309401
TI  - Effects of amoxicillin/clavulanic acid on the pharmacokinetics of valproic acid.
AB  - Valproic acid (VPA) is mainly metabolized via glucuronide, which is hydrolyzed by
      beta-glucuronidase and undergoes enterohepatic circulation.
      Amoxicillin/clavulanic acid (AMC) administration leads to decreased levels of
      beta-glucuronidase-producing bacteria, suggesting that these antibiotics could
      interrupt enterohepatic circulation and thereby alter the pharmacokinetics of
      VPA. This study aimed to evaluate the effects of AMC on the pharmacokinetics of
      VPA. This was an open-label, two-treatment, one-sequence study in 16 healthy
      volunteers. Two treatments were evaluated; treatment VPA, in which a single dose
      of VPA 500 mg was administered, and treatment AMC + VPA, in which multiple doses
      of AMC 500/125 mg were administered three times daily for 7 days and then a
      single dose of VPA was administered. Blood samples were collected up to 48 hours.
      Pharmacokinetic parameters were calculated using noncompartmental methods.
      Fifteen subjects completed the study. Systemic exposures and peak concentrations
      of VPA were slightly lower with treatment AMC + VPA than with treatment VPA
      (AUClast, 851.0 h.mg/L vs 889.6 h.mg/L; C max, 52.1 mg/L vs 53.0 mg/L). There
      were no significant between-treatment effects on pharmacokinetics (95% confidence
      interval [CI]) of AUClast and C max (95.7 [85.9-106.5] and 98.3 [91.6-105.6],
      respectively). Multiple doses of AMC had no significant effects on the
      pharmacokinetics of VPA; thus, no dose adjustment is necessary. 

PMID- 26309402
TI  - Therapeutic designed poly (lactic-co-glycolic acid) cylindrical oseltamivir
      phosphate-loaded implants impede tumor neovascularization, growth and metastasis
      in mouse model of human pancreatic carcinoma.
AB  - Poly (lactic-co-glycolic acid) (PLGA) copolymers have been extensively used in
      cancer research. PLGA can be chemically engineered for conjugation or
      encapsulation of drugs in a particle formulation. We reported that oseltamivir
      phosphate (OP) treatment of human pancreatic tumor-bearing mice disrupted the
      tumor vasculature with daily injections. Here, the controlled release of OP from
      a biodegradable PLGA cylinder (PLGA-OP) implanted at tumor site was investigated
      for its role in limiting tumor neovascularization, growth, and metastasis. PLGA
      OP cylinders over 30 days in vitro indicated 20%-25% release profiles within 48
      hours followed by a continuous metronomic low dose release of 30%-50% OP for an
      additional 16 days. All OP was released by day 30. Surgically implanted PLGA-OP
      containing 20 mg OP and blank PLGA cylinders at the tumor site of heterotopic
      xenografts of human pancreatic PANC1 tumors in RAGxCgamma double mutant mice
      impeded tumor neovascularization, growth rate, and spread to the liver and lungs
      compared with the untreated cohort. Xenograft tumors from PLGA and PLGA-OP
      treated cohorts expressed significant higher levels of human E-cadherin with
      concomitant reduced N-cadherin and host CD31(+) endothelial cells compared with
      the untreated cohort. These results clearly indicate that OP delivered from PLGA
      cylinders surgically implanted at the site of the solid tumor show promise as an
      effective treatment therapy for cancer. 

PMID- 26309403
TI  - Exenatide once-weekly injection for the treatment of type 2 diabetes in Chinese
      patients: current perspectives.
AB  - Glucagon-like peptide-1 (GLP-1) analogs, such as exenatide, have played an
      important role as antidiabetic medications in the treatment of type 2 diabetes
      (T2DM). Like most other hypoglycemic agents, exenatide has a number of actions,
      including lowering blood glucose, promoting weight loss, improving insulin
      resistance, and protecting islet beta-cells. Although GLP-1 analogs, combined
      with other antidiabetic medications, have excellent performance in T2DM, some
      side effects and imperfections limit its use in clinical practice. Since 2012, a
      new generation GLP-1 agent, exenatide once weekly (QW), has been available for
      patients with T2DM in the USA, but not as yet in the People's Republic of China.
      Previous data indicate that exenatide QW achieves better fasting glucose
      reductions than sitagliptin or exenatide twice daily, whilst appearing non
      inferior to pioglitazone and achieving less reductions than insulin glargine.
      Exenatide QW was better at improving average postprandial glucose than
      sitagliptin or titrated insulin glargine, but was inferior to exenatide twice
      daily. Additionally exenatide QW has a better effect in terms of weight loss than
      other glycemic medications. Exenatide QW can also reduce blood lipids and lower
      blood pressure. Accordingly, exenatide QW is cost-effective, achieves good
      clinical outcomes, and has acceptable side effects, indicating that it has
      promising prospects for future use in the People's Republic of China. 

PMID- 26309404
TI  - A review of the clinical utility of duloxetine in the treatment of diabetic
      peripheral neuropathic pain.
AB  - Diabetes mellitus is a world-wide epidemic with many long-term complications,
      with neuropathy being the most common. In particular, diabetic peripheral
      neuropathic pain (DPNP), can be one of the most distressing complications
      associated with diabetes, leading to decreases in physical and mental quality of
      life. Despite the availability of many efficient medications, DPNP remains a
      challenge to treat, and the optimal sequencing of pharmacotherapy remains
      unknown. Currently, there are only three medications approved by the US Food and
      Drug Administration specifically for the management of DPNP. Duloxetine (DUL), a
      selective serotonin-norepinephrine reuptake inhibitor, is one of these. With the
      goal of optimizing pharmacotherapy use in DPNP population, a review of current
      literature was conducted, and the clinical utility of DUL described. Along with
      early clinical trials, recently published observational studies and
      pharmacoeconomic models may be useful in guiding decision making by clinicians
      and managed care organizations. In real-world practice settings, DUL is
      associated with decreased or similar opioid utilization, increased medication
      adherence, and similar health care costs compared with current standard of care.
      DUL has consistently been found to be a cost-effective option over short time
      horizons. Currently, the long-term cost-effectiveness of DUL is unknown. Evidence
      derived from randomized clinical trials, real-world observations, and economic
      models support the use of DUL as a first-line treatment option from the
      perspective of the patient, clinician, and managed care payer. 

PMID- 26309405
TI  - Impact of Expression Levels of Platinum-uptake Transporters Copper Transporter 1
      and Organic Cation Transporter 2 on Resistance to Anthracycline/Taxane-based
      Chemotherapy in Triple-negative Breast Cancer.
AB  - Adding platinum drugs to anthracycline/taxane (ANC-Tax)-based neoadjuvant
      chemotherapy (NAC) improves pathological complete response (pCR) rates in triple
      negative breast cancer (TNBC). Copper transporter 1 (CTR1) and organic cation
      transporter 2 (OCT2) critically affect the uptake and cytotoxicity of platinum
      drugs. We immunohistochemically determined CTR1 and OCT2 levels in pre
      chemotherapy biopsies from 105 patients with HER2-negative breast cancer treated
      with ANC-Tax-based NAC. In the TNBC group, Ki-67(high) [pathological good
      response (pGR), P = 0.04] was associated with response, whereas CTR1(high) (non
      pGR, P = 0.03), OCT2(high) (non-pGR, P = 0.01; non-pCR, P = 0.03), and combined
      CTR1(high) and/or OCT2(high) (non-pGR, P = 0.005; non-pCR, P = 0.003) were
      associated with non-response. In multivariate analysis, Ki-67(high) was an
      independent factor for pGR and CTR1 for non-pGR. Combined CTR1/OCT2 was a strong
      independent factor for non-pGR. However, no variables were associated with
      response in luminal BC. These results indicate that platinum uptake transporters
      are predominantly expressed in ANC-Tax-resistant TNBCs, which implies that
      advantage associated with adding platinum drugs may depend on high drug uptake. 

PMID- 26309406
TI  - Incidence and Potential Significance of Internal Mammary Lymphadenopathy on
      Computed Tomography in Patients with a Diagnosis of Primary Breast Cancer.
AB  - INTRODUCTION: The importance of internal mammary nodes (IMNs) in the staging and
      treatment of breast cancer patients is controversial. METHODS: A retrospective
      cohort of patients diagnosed with primary breast cancer over a 4-year period
      (January 2009 to December 2012) was assessed. The number and size of any IMNs
      visible on spiral computed tomography (CT) were recorded. RESULTS: A total of 830
      patients were diagnosed with primary breast cancer within the identified time
      frame, of which 150 patients met the inclusion criteria. Of these 42% (63) had
      IMNs present, although the majority were small (<5 mm). However, 16% (25) had
      larger nodes, greater than 5 mm in short axis, present on CT. Significantly more
      patients with the presence of large (>5 mm) IMNs had more advanced disease with
      CT evidence of other distant spread. CONCLUSION: We have demonstrated that IMNs
      are present in a substantial number of our primary breast cancer patients. We
      suggest that further histological research is required to establish reliable CT
      size criterion for pathological IMNs. In addition, routine imaging of the IM
      chain, as well as axilla, should be considered in the staging of breast cancer.

PMID- 26309407
TI  - A Quantitative Perspective on Surface Marker Selection for the Isolation of
      Functional Tumor Cells.
AB  - Much effort has gone into developing fluid biopsies of patient peripheral blood
      for the monitoring of metastatic cancers. One common approach is to isolate and
      analyze tumor cells in the peripheral blood. Widespread clinical implementation
      of this approach has been hindered by the current choice of targeting epithelial
      markers known to be highly variable in primary tumor sites. Here, we review
      current antigen-based tumor cell isolation strategies and offer biological
      context for commonly studied cancer surface markers. Expression levels of the
      most common markers are quantitated for three breast cancer and two non-small
      cell lung cancer (NSCLC) lineage models. These levels are contrasted with that
      present on healthy peripheral blood mononuclear cells (PBMC) for comparison to
      expected background levels in a fluid biopsy setting. A key feature of this work
      is establishing a metric of markers per square micrometer. This describes an
      average marker density on the cell membrane surface, which is a critical metric
      for emerging isolation strategies. These results serve to extend expression of
      key tumor markers in a sensitive and dynamic manner beyond traditional
      positive/negative immunohistochemical staining to guide future fluid biopsy
      targeting strategies. 

PMID- 26309408
TI  - High Skp2/Low p57(Kip2) Expression is Associated with Poor Prognosis in Human
      Breast Carcinoma.
AB  - Downregulation of p57(Kip2) is involved in tumor progression, and S-phase kinase
      associated protein 2 (Skp2) is an E3 ligase that regulates a variety of cell
      cycle proteins. However, the prognostic value of p57(Kip2) and its correlation
      with Skp2 in breast cancer have not been fully elucidated. Here we report our
      study on the expression of p57(Kip2) and Skp2 in 102 breast cancer patients by
      immunohistochemistry, and analysis of clinicopathologic parameters in relation to
      patient prognosis. The expression of p57(Kip2) was negatively associated with
      Skp2 expression in breast cancer (r = -0.26, P = 0.009). Kaplan-Meier analysis
      indicated that both high Skp2 and low p57(Kip2) correlated with poor disease-free
      survival (DFS) (P = 0.05), and a group with the combination of high Skp2/low
      p57(Kip2) demonstrated even worse DFS (log-rank = 21.118, P < 0.001). In
      addition, univariate analysis showed that Skp2, p57(Kip2), histological grade,
      lymph node metastasis, and estrogen and progesterone receptors (ER and PR) were
      all associated with DFS, and multivariate analysis revealed that lymph node
      metastasis and Skp2 were independent prognostic biomarkers. The correlation
      between p57 and Skp2 was further demonstrated in multiple breast cancer cell
      lines and cell cycle phases. Half-life and immunoprecipitation (IP) experiments
      indicated that Skp2 directly interacts with p57(Kip2) and promotes its
      degradation, rather than its mutant p57(Kip2) (T310A). Overall, our findings
      demonstrate that Skp2 directly degrades p57(Kip2), and an inverse correlation
      between these proteins (high skp2/low p57(Kip2)) is associated with poor
      prognosis in breast cancer. Thus, our results indicate a combined prognostic
      value of these markers in breast cancer diagnosis and treatment. 

PMID- 26309409
TI  - Use of Targeted Liposome-based Chemotherapeutics to Treat Breast Cancer.
AB  - The use of nanocarriers such as liposomes to deliver anticancer drugs to tumors
      can significantly enhance the therapeutic index of otherwise unencapsulated
      cytotoxic agents. This is in part because of the fact that the phospholipid
      bilayer can protect healthy sensitive tissue from the damaging effects of these
      types of drugs. Furthermore, the ease with which the phospholipid bilayer surface
      can be modified to allow for polyethylene glycol incorporation resulting in
      pegylated liposomes allow for increased circulation times in vivo, and thus an
      overall increase in the concentration of the drug delivered to the tumor site.
      This explains the clinical success of the liposomal-based drug Doxil, which has
      proven to be quite efficacious in the treatment of breast cancer. However,
      significant challenges remain involving poor drug transfer between the liposome
      and tumor cells with this type of nontargeted drug delivery system. Thus, future
      work involves the development of "smart" drugs, or targeted drug delivery
      intended for improved colocalization between the drug and cancerous cells. While
      it is not possible to entirely discuss such a rapidly growing field of study
      involving many different types of chemotherapeutics here, in this review, we
      discuss some of the recent advancements involving the development of targeted
      liposome-based chemotherapeutics to treat breast cancer. 

PMID- 26309410
TI  - Multidisciplinary Prognostication Using the Palliative Prognostic Score in an
      Australian Cancer Center.
AB  - CONTEXT: Accurate prognostication is important in oncology and palliative care. A
      multidisciplinary approach to prognostication provides a novel approach, but its
      accuracy and application is poorly researched. In this study, we describe and
      analyze our experience of multidisciplinary prognostication in palliative care
      patients with cancer. OBJECTIVES: To assess our accuracy of prognostication using
      multidisciplinary team prediction of survival (MTPS) alone and within the
      Palliative Prognostic (PaP) Score. METHODS: This retrospective study included all
      new patients referred to a palliative care consultation service in a tertiary
      cancer center between January 2010 and December 2011. Initial assessment data for
      421 inpatients and 223 outpatients were analyzed according to inpatient and
      outpatient groups to evaluate the accuracy of prognostication using MTPS alone
      and within the PaP score (MTPS-PaP) and their correlation with overall survival.
      RESULTS: Inpatients with MTPS-PaP group A, B, and C had a median survival of
      10.9, 3.4, and 0.7 weeks, respectively, and a 30-day survival probability of 81%,
      40%, and 10%, respectively. Outpatients with MTPS-PaP group A and B had a median
      survival of 17.3 and 5.1 weeks, respectively, and a 30-day survival probability
      of 94% and 50%, respectively. MTPS overestimated survival by a factor of 1.5 for
      inpatients and 1.2 for outpatients. The MTPS-PaP score correlated better than
      MTPS alone with overall survival. CONCLUSION: This study suggests that a
      multidisciplinary team approach to prognostication within routine clinical
      practice is possible and may substitute for single clinician prediction of
      survival within the PaP score without detracting from its accuracy.
      Multidisciplinary team prognostication can assist treating teams to recognize and
      articulate prognosis, facilitate treatment decisions, and plan end-of-life care
      appropriately. PaP was less useful in the outpatient setting, given the longer
      survival interval of the outpatient palliative care patient group.

PMID- 26309412
TI  - The histone demethylase PHF8 promotes prostate cancer cell growth by activating
      the oncomiR miR-125b.
AB  - AIMS: Prostate cancer (PCa) is the most frequently diagnosed malignancy in men.
      However, the underlying mechanism is not fully understood. In this study, we aim
      to research the molecular mechanisms underlying the initiation and progression of
      PCa. RESULTS: Plant homeodomain finger protein 8 (PHF8) is upregulated in human
      PCa tissues and cell lines. PHF8 knockdown attenuates growth and cellular
      transformation of PCa cells. PHF8 depletion induces PCa cell apoptosis by
      activating proapoptotic proteins and inactivating antiapoptotic proteins.
      Furthermore, miR-125b is a target of PHF8, and miR-125b seems to be essential for
      the hyper proliferation of PCa cells in the presence of PHF8. CONCLUSION: In
      conclusion, we identify the histone demethylase PHF8 as an oncogenic protein in
      human PCa. These findings indicate PHF8 as a potential candidate for clinical
      intervention.

PMID- 26309411
TI  - Tryptophan Catabolism in Chronic Viral Infections: Handling Uninvited Guests.
AB  - l-Tryptophan (l-Trp) is an essential amino acid that possesses diverse metabolic,
      neurological, and immunological roles spanning from the synthesis of proteins,
      neurotransmitter serotonin, and neurohormone melatonin, to its degradation into
      immunosuppressive catabolites by indoleamine-2, 3-dioxygenase (IDO) in the
      kynurenine pathway (KP). Trp catabolites, by activating aryl hydrocarbon receptor
      (AhR), play an important role in antimicrobial defense and immune regulation.
      IDO/AhR acts as a double-edged sword by both depleting l-Trp to starve the
      invaders and by contributing to the state of immunosuppression with
      microorganisms that were not cleared during acute infection. Pathogens
      experiencing Trp deprivation by IDO-mediated degradation include certain
      bacteria, parasites, and less likely viruses. However, chronic viral infections
      highjack the host immune response to create a state of disease tolerance via
      kynurenine catabolites. This review covers the latest data involving chronic
      viral infections such as human immunodeficiency virus (HIV), hepatitis B virus
      (HBV), hepatitis C virus (HCV), herpes, and cytomegalovirus (CMV) and their
      cellular interplay with Trp catabolites. Strategies developed by viruses to
      escape immune control also represent new avenues for therapeutic interventions
      based on Trp metabolism. 

PMID- 26309413
TI  - A polymorphism at the microRNA binding site in the 3' untranslated region of RYR3
      is associated with outcome in hepatocellular carcinoma.
AB  - OBJECTIVE: MicroRNAs can bind to the 3' untranslated regions (UTRs) of messenger
      RNAs, where they interfere with the translation of targeting genes, thereby
      regulating cell differentiation, apoptosis, and tumorigenesis. In this study,
      three microRNA binding site single nucleotide polymorphisms (SNPs) located in the
      3' UTR of RYR3 (rs1044129), C14orf101 (rs4901706), and KIAA0423 (rs1053667) were
      genotyped to assess their relationships with the risks and outcomes of
      hepatocellular carcinoma (HCC). METHODS: The SNPs were genotyped with the
      ligation detection reaction method. Renilla luciferase reporter assays were used
      to measure the binding affinity between microRNA 367 and RYR3. Survival curves
      were calculated using the Kaplan-Meier method, and comparisons between the curves
      were made using the log-rank test. Multivariate survival analysis was performed
      using a Cox proportional hazards model. RESULTS: It was found that rs1044129 at
      the 3' UTR of RYR3 was related to postoperative survival in HCC, with the AA type
      associated with longer survival times as per the log-rank test. After adjusting
      with the Cox model, rs104419 was identified as an independent predictor of HCC
      survival (relative risk: 1.812; 95% confidence interval: 1.026-3.201; P=0.041).
      Luciferase analysis also indicated the different binding affinities between the
      SNPs of rs1044129 and microRNA 367. CONCLUSION: The SNP in the microRNA binding
      site of RYR3 can be used as a valuable biomarker when predicting HCC outcomes.

PMID- 26309414
TI  - Heme oxygenase-1 is a predictive biomarker for therapeutic targeting of advanced
      clear cell renal cell carcinoma treated with sorafenib or sunitinib.
AB  - BACKGROUND: We analyzed the expression of heme oxygenase-1 (HO-1) in patients
      undergoing radical nephrectomy for advanced clear cell renal cell carcinoma (CC
      RCC) and evaluated the effects of the targeted therapies treated with sorafenib
      and sunitinib. METHODS: Expression of HO-1 in cancer tissue from 66 patients was
      measured by immunohis-tochemical staining. The patients received either oral
      sorafenib (n=40) or oral sunitinib (n=26) within 4 weeks after nephrectomy and
      were followed up long term to determine the tumor response and prognosis.
      RESULTS: Our current study revealed a high HO-1 expression level in 57.6% (38/66)
      of patients and a low HO-1 expression level in 42.4% (28/66) of patients with CC
      RCC. The study also revealed that patients with high HO-1 expression did not have
      a higher objective response rate (2.6% versus 53.6%, P<0.01), clinical benefit
      rate (47.4% versus 92.9%, P<0.01), longer progression-free survival (4.4 versus
      42 months, P=0.022), or overall survival (chi (2)=4.775, P=0.029) than patients
      with low HO-1 expression. In the low HO-1 level group, a higher tumor response
      rate and a longer survival time was achieved in patients who received sorafenib
      or sunitinib. Multivariate analysis showed that HO-1 expression was an
      independent prognostic factor for tumor response and overall survival.
      CONCLUSION: High expression of HO-1 was associated with a lower tumor response
      rate and a shorter overall survival time when compared with low expression of HO
      1. Overall, HO-1 expression might be a useful biomarker for predicting the
      response to sunitinib and sorafenib for patients with metastatic CC-RCC.

PMID- 26309415
TI  - Profile of lebrikizumab and its potential in the treatment of asthma.
AB  - Interleukin (IL)-13 has been associated with multiple inflammatory features of
      asthma. It affects multiple cellular lines in asthma and is a key mediator in
      airway hyperreactivity and remodeling. Periostin, an extracellular protein, has
      been used as a surrogate marker of IL-13 activity and has been linked to airway
      remodeling by inducing subepithelial fibrosis. Lebrikizumab is a humanized
      monoclonal antibody that targets IL-13. Studies have demonstrated promising
      results with lebrikizumab therapy in asthma with regard to pulmonary function and
      exacerbation rates, especially on those patients with surrogate markers of T
      helper cell type 2-driven inflammation (ie, elevated immunoglobulin E levels,
      eosinophil counts, periostin levels). Lebrikizumab appears to be a safe therapy,
      but there are ongoing studies evaluating its efficacy and safety profile. Other
      therapies that target IL-13 and the receptor of IL-4/IL-13 have been studied, but
      future studies are needed to determine their role in the treatment of asthma. 

PMID- 26309416
TI  - Economic evaluations of personalized medicine: existing challenges and current
      developments.
AB  - Personalized medicine, with the aim of safely, effectively, and cost-effectively
      targeting treatment to a prespecified patient population, has always been a long
      time goal within health care. It is often argued that personalizing treatment
      will inevitably improve clinical outcomes for patients and help achieve more
      effective use of health care resources. Demand is increasing for demonstrable
      evidence of clinical and cost-effectiveness to support the use of personalized
      medicine in health care. This paper begins with an overview of the existing
      challenges in conducting economic evaluations of genetics- and genomics-targeted
      technologies, as an example of personalized medicine. Our paper illustrates the
      complexity of the challenges faced by these technologies by highlighting the
      variations in the issues faced by diagnostic tests for somatic variations,
      generally referring to genetic variation in a tumor, and germline variations,
      generally referring to inherited genetic variation in enzymes involved in drug
      metabolic pathways. These tests are typically aimed at stratifying patient
      populations into subgroups on the basis of clinical effectiveness (response) or
      safety (avoidance of adverse events). The paper summarizes the data requirements
      for economic evaluations of genetics and genomics-based technologies while
      outlining that the main challenges relating to data requirements revolve around
      the availability and quality of existing data. We conclude by discussing current
      developments aimed to address the challenges of assessing the cost-effectiveness
      of genetics and genomics-based technologies, which revolve around two central
      issues that are interlinked: the need to adapt available evaluation methods and
      identifying who is responsible for generating evidence for these technologies. 

PMID- 26309417
TI  - Olaparib in the management of ovarian cancer.
AB  - Alterations in the homologous repair pathway are thought to occur in 30%-50% of
      epithelial ovarian cancers. Cells deficient in homologous recombination rely on
      alternative pathways for DNA repair in order to survive, thereby providing a
      potential target for therapy. Olaparib, a poly(ADP-ribose) polymerase (PARP)
      inhibitor, capitalizes on this concept and is the first drug in its class
      approved for patients with ovarian cancer. This review article will provide an
      overview of the BRCA genes and homologous recombination, the role of PARP in DNA
      repair and the biological rationale for the use of PARP inhibitors as cancer
      therapy, and ultimately will focus on the use of olaparib in the management of
      ovarian cancer. 

PMID- 26309419
TI  - Getting to the Heart of the Matter: An Overview of Cardiac Toxicity Related to
      Cancer Therapy.
AB  - With the improvement in cancer survival, long-term cardiotoxicity has become an
      area of increased interest. Various cancer therapies, including chemotherapy and
      radiation therapy can lead to cardiac toxicities with both acute and chronic
      manifestations. Awareness and early recognition can lead to improvement in
      cardiac survival and patient outcomes. The focus of this review is to summarize
      the cancer therapy agents most often associated with cardiovascular side effects,
      highlighting their mechanism of action and strategies for surveillance and
      prevention. 

PMID- 26309420
TI  - A Case of Fascioliasis Treated Successfully Without Sequelae in a Japanese
      Expatriate Living in Jakarta.
AB  - A 46-year-old Japanese female expatriate living in Jakarta presented with
      intermittent fever lasting for a month. Although she was considered at low risk
      of Fasciola spp. infection because she lived in an upper-class residential area
      of the city, the patient presented with eosinophilia after consuming organic raw
      vegetables; in addition, contrast-enhanced computed tomography detected
      microabscesses in a tractlike pattern in the liver. These findings led to an
      early diagnosis of fascioliasis, which was successfully treated without sequelae.
      In any patient with a history of consuming raw vegetables, fascioliasis should be
      suspected regardless of where the patient has lived. 

PMID- 26309418
TI  - Bedside-to-Bench Translational Research for Chronic Heart Failure: Creating an
      Agenda for Clients Who Do Not Meet Trial Enrollment Criteria.
AB  - Congestive heart failure (CHF) is a chronic condition usually without cure.
      Significant developments, particularly those addressing pathophysiology, mainly
      started at the bench. This approach has seen many clinical observations initially
      explored at the bench, subsequently being trialed at the bedside, and eventually
      translated into clinical practice. This evidence, however, has several
      limitations, importantly the generalizability or external validity. We now
      acknowledge that clinical management of CHF is more complicated than merely
      translating bench-to-bedside evidence in a linear fashion. This review aims to
      help explore this evolving area from an Australian perspective. We describe the
      continuation of research once core evidence is established and describe how
      clinician-scientist collaboration with a bedside-to-bench view can help enhance
      evidence translation and generalizability. We describe why an extension of the
      available evidence or generating new evidence is occasionally needed to address
      the increasingly diverse cohort of patients. Finally, we explore some of the
      tools used by basic scientists and clinicians to develop evidence and describe
      the ones we feel may be most beneficial. 

PMID- 26309421
TI  - Antineutrophil Cytoplasmic Antibody-associated Glomerulonephritis Complicated by
      Pneumatosis Intestinalis.
AB  - Pneumatosis intestinalis is a characteristic imaging phenomenon indicating the
      presence of gas in the bowel wall. The link between pneumatosis intestinalis and
      various kinds of autoimmune diseases has been reported anecdotally, while
      information regarding the cases with antineutrophil cytoplasmic antibodies (ANCA)
      associated vasculitis complicated by concurrent pneumatosis intestinalis is
      lacking. In this report, we describe our serendipitous experience with one such
      case of pneumatosis intestinalis in a patient with ANCA-associated
      glomerulonephritis. We also discuss several therapeutic concerns that arose in
      the current case, which had an impact on the pathogenesis of the disease. 

PMID- 26309422
TI  - Pleural Fluid Analysis in Chronic Hemothorax: A Mimicker of Infection.
AB  - OBJECTIVES: Timing to video-assisted thoracoscopic surgery (VATS) in hemothorax
      is based on preventing acute and long-term complications of retained blood
      products in the pleural space, including pleural space infection. We propose that
      the persistence of blood in the pleural space induces a proinflammatory state,
      independent of active infection. METHODS: We identified six patients with a
      hemothorax by clinical history, radiographic imaging, and pleural fluid analysis
      from a database of 1133 patients undergoing thoracentesis from 2002 to 2010 at
      the Medical University of South Carolina. RESULTS: In four of the six patients
      identified, the time from injury to thoracentesis was one, four, four, and five
      days, respectively. The fluid pH range was 7.32-7.41. The lactate dehydrogenase
      (LDH) range was 210-884 IU/L (mean 547 IU/L), and the absolute neutrophil count
      (ANC) range was 1196-3631 cells/uL. In two patients, the time from injury to
      thoracentesis was 7 and 60 days. In these two patients, the pH was 7.18 and 6.91,
      LDH was 1679 and 961 IU/L, and the ANC was 8134 and 5943 cells/uL. Microbiology
      and pathology were negative in all patients. CONCLUSIONS: The persistence of
      blood outside the vascular compartment, and within the pleural space,
      biochemically mirrors infection. We will explore the multiple mechanisms that
      account for development of pleural fluid acidosis, inflammation, and neutrophil
      recruitment.

PMID- 26309423
TI  - Phenobarbital and Phototherapy Combination Enhances Decline of Total Serum
      Bilirubin and May Decrease the Need for Blood Exchange Transfusion in Newborns
      with Isoimmune Hemolytic Disease.
AB  - OBJECTIVE: The objective of this study was to evaluate the effect of
      phenobarbital and phototherapy combination on the total serum bilirubin of the
      newborn infants with isoimmune hemolytic disease (IHD) and its impact on blood
      exchange transfusion rates. PATIENTS AND METHOD: This single-blinded,
      prospective, randomized, controlled trial was conducted between March 2013 and
      December 2014 at the pediatric ward of two Military Hospitals in Jordan. A total
      of 200 full-term neonates with IHD were divided randomly into two groups: (1) the
      phenobarbital plus phototherapy group (n = 103), and (2) the phototherapy-only
      group (n = 97). Infants in group 1 received an oral dose of 2.5 mg/kg
      phenobarbital every 12 hours for 3 days in addition to phototherapy. The total
      serum bilirubin was observed. RESULTS: Of the total 200 included newborn infants,
      186 infants completed the study: 97 infants were included in group 1 and 89
      infants in group 2. The difference between the mean total serum bilirubin levels
      at 24, 48, and 72 hours after starting the trial was clinically and statistically
      significant at P < 0.05. The differences between the two groups were also
      statistically significant at P < 0.05. Of the total 186 who completed the study,
      only 22 underwent blood exchange transfusion [7 from group 1, and 15 from group 2
      (P = 0.0478)]. CONCLUSION: In a limited-resources setting, phenobarbital in
      combination with phototherapy may be helpful to newborn infants with IHD, as it
      results in a faster decline in total serum bilirubin, thus decreasing the need
      for blood exchange transfusion than phototherapy alone.

PMID- 26309424
TI  - Pattern of Adverse Drug Reactions in Children Attending the Department of
      Pediatrics in a Tertiary Care Center: A Prospective Observational Study.
AB  - AIM: To study the pattern of various adverse drug reactions (ADRs) occurring in
      children attending the Department of Pediatrics, SMGS Hospital, Jammu over 1
      year. SUBJECTS AND METHODS: This was a prospective study, with study population
      of patients attending Department of Pediatrics over a period of 1 year. A
      structured format was used to enroll the participants. A pilot study was
      conducted to test the suitability of the format and feasibility of the study. The
      study was carried out to review various pattern of ADRs by using the Naranjo
      probability scale, and severity was assessed by using the Hartwig severity scale.
      ADRs were classified according to the classification used by the Adverse Drug
      Reaction Monitoring Center, Central Drugs Standard Control Organization, New
      Delhi, India. RESULTS: In the present study, 104 patients were found to have
      developed acute drug reactions. Among these, 83.6% were type B, 14.42% type A,
      and 1.92% were type U. Furthermore, 25.96% ADRs were due to anticonvulsants,
      followed by antibiotics (22.11%), antipyretics (11.53%), vaccination (8.65%),
      steroids (6.73%), decongestants (5.67%), snake antivenom and antiemetics (3.84%),
      and fluids, insulin, and antacids (1.92%). The patients' dermatological system
      was involved in 67.30%, followed by the central nervous system (CNS) in 11.53%
      patients. Renal system was involved in 6.73% patients. Cardiac, musculoskeletal,
      metabolic, and other systems were involved in 4.80%, 3.84%, 2.88%, and 0.96%,
      respectively. According to the Hartwig severity scale of ADRs, 64.4% patients had
      moderate ADRs, 29.8% patients had severe ADRs, and 5.76% had mild ADRs. In the
      present study, 64.4% patients expressed moderate severity, whereas 29.8%
      expressed high severity and 5.76% expressed mild ADRs. CONCLUSION: ADRs were seen
      in 71% of the patients between 1 and 5 years of age, 26% in the age group of 5-10
      years, and 3% were more than 10 years old. Anticonvulsants (25.96%) and
      antibiotics (22.11%) were responsible for majority of ADRs. Rash (55.76%) was the
      most common presentation of ADR. Owing to the high number of ADRs, the present
      study points to the need for rigid adverse drug monitoring among pediatric
      patients to ensure the safety of drug therapy.

PMID- 26309425
TI  - Method of transportation and drinking among club patrons.
AB  - OBJECTIVE: The current study examines the variation in alcohol use among
      nightclub patrons under three transportation conditions: those who departed from
      a club using modes of transportation other than cars or motorcycles (e.g.,
      pedestrians, bicyclists, subway riders); those who were passengers of drivers
      (auto/taxi passenger patrons); and those who drove from the club (driving
      patrons). We seek to determine whether patrons' choice for how to leave the club
      contributes to their risk, as assessed by blood alcohol concentrations (BAC),
      after controlling for other factors that may contribute to their BAC including
      demographic characteristics and social drinking group influences. METHODS: Data
      were collected from social drinking groups as they entered and exited clubs for
      71 different evenings at ten clubs from 2010 through 2012. Using portal
      methodology, a research site was established proximal to club entrances. Each
      individual participant provided data on themselves and others in their group. The
      present analyses are based upon 1833 individuals who completed both entrance and
      exit data. Our outcome variable is blood alcohol content (BAC) based upon breath
      tests attained from patrons at entrance and exit from the club. Independent
      variables include method of transportation, social group characteristics, drug
      use, and personal characteristics. We use step-wise multiple regressions to
      predict entrance BAC, change in BAC from entrance to exit, and exit BAC: first
      entering individual demographic characteristics, then entering group
      characteristics, then drug use, and finally entering method of transportation
      (two dummy coded variables such that drivers are the referent category). RESULTS:
      In sum, in all three of our analyses, only three variables are consistently
      predictive of BAC: presence of a group member who is frequently drunk and non
      driving modes of transportation, either being the passenger or taking alternate
      methods of transportation. In particular, taking an alternate form of
      transportation was consistently and strongly predictive of higher BAC.
      CONCLUSIONS: Additional public health messages are needed to address patrons who
      are no longer drinking and driving but who are nonetheless engaged in high levels
      of drinking that may lead to various risky outcomes, for example: being targeted
      for physical and/or sexual assault, pedestrian accidents, and other adverse
      consequences. These risks are not addressed by the focus on drinking and driving.
      Key messages appropriate for patrons who use alternate transportation might
      include devising a safety plan before entering the club and a focus on sobering
      up before leaving.

PMID- 26309426
TI  - Antitumoral potency of methanolic extract from Nitraria retusa leaves via its
      immunomodulatory effect.
AB  - BACKGROUND: The purpose of this study was to assess the antitumoral effect of the
      methanol extract (MeOH) from Nitraria retusa leaves and to investigate its
      immunomodulatory activity that mediated the prevention of tumor progression in
      tumor-bearing mice. METHODS: Balb/c mice weighing 18-20 g were subcutaneously
      implanted with B16-F10 cells then injected intra-peritoneally, 7 days later with
      (200 mg/kg bw) of MeOH extract, for 21 days. After euthanization on day 21, the
      tumors were weighed. Lymphocyte proliferation, cytotoxic T lymphocyte (CTL) and
      NK activity were evaluated using the MTT assay. Macrophage phagocytosis was
      studied by measuring their lysosomal activity and nitric oxide production.
      RESULTS: The methanol extract inhibited significantly the growth of the implanted
      tumor, and increased remarkably splenocyte proliferation as well as NK and CTL
      activities, in tumor-bearing mice. It also promoted lysosomal activity of treated
      animal macrophages. CONCLUSION: Our findings suggest that antitumoral effect of
      MeOH extract is related with to immunomodulatory activity.

PMID- 26309427
TI  - Multiple causes of death analysis of chronic diseases: the example of diabetes.
AB  - BACKGROUND: Identifying a single disease as the underlying cause of death (UCOD)
      is an oversimplification of the clinical-pathological process leading to death.
      The multiple causes of death (MCOD) approach examines any mention of a disease in
      death certificates. Taking diabetes as an example, the study investigates:
      patterns of death certification, differences in mortality figures based on the
      UCOD and on MCOD, factors associated to the mention of diabetes in death
      certificates, and potential of MCOD in the analysis of the association between
      chronic diseases. METHODS: The whole mortality archive of the Veneto Region-Italy
      was extracted from 2008 to 2010. Mortality rates and proportional mortality were
      computed for diabetes as the UCOD and as MCOD. The position of the death
      certificate where diabetes was mentioned was analyzed. Conditional logistic
      regression was applied with chronic liver diseases (CLD) as the outcome and
      diabetes as the exposure variable. A subset of 19,605 death certificates of known
      diabetic patients (identified from the archive of exemptions from medical
      charges) was analyzed, with mention of diabetes as the outcome and
      characteristics of subjects as well as other diseases reported in the certificate
      as predictors. RESULTS: In the whole mortality archive, diabetes was mentioned in
      12.3 % of death certificates, and selected as the UCOD in 2.9 %. The death rate
      for diabetes as the UCOD was 26.8 * 10(5) against 112.6 * 10(5) for MCOD; the
      UCOD/MCOD ratio was higher in males. The major inconsistencies of certification
      were entering multiple diseases per line and reporting diabetes as a consequence
      of circulatory diseases. At logistic regression the mention of diabetes was
      associated with the mention of CLD (mainly non-alcohol non-viral CLD). In the
      subset of known diabetic subjects, diabetes was reported in 52.1 %, and selected
      as the UCOD in 13.4 %. The probability of reporting diabetes was higher with
      coexisting circulatory diseases and renal failure and with long duration of
      diabetes, whereas it was lower in the presence of a neoplasm. CONCLUSIONS: The
      use of MCOD makes the analysis of mortality data more complex, but conveys more
      information than usual UCOD analyses.

PMID- 26309428
TI  - Assessment of nicotine dependence among smokers in Nepal: a community based cross
      sectional study.
AB  - BACKGROUND: The Fagerstrom Test for Nicotine Dependence (FTND) and Heaviness of
      Smoking Index (HSI) are extensively used methods to measure the severity of
      nicotine dependence among smokers. The primary objective of the study was to
      assess the nicotine dependence amongst currently smoking Nepalese population.
      METHODS: A community based cross-sectional study was conducted between August and
      November 2014. Information was collected using semi-structured questionnaire from
      three districts of Nepal. Data on demographic characteristics, history of tobacco
      use and level of nicotine dependence were collected from 587 smokers through face
      to face interviews and self-administered questionnaires. Non-parametric test were
      used to compare significant differences among different variables. RESULTS: The
      median age of respondents was 28 (Inter-Quartile Range: 22-40) years and the
      median duration of smoking was 10 (5-15) years. Similarly, the median age for
      smoking initiation was 16 (13-20) years and the median smoking pack year was 4.2
      (1.5-12). One third of the respondents consumed smokeless tobacco products. Half
      of the respondents wanted to quit smoking. The median score for FTND and HSI was
      4 (2-5) and 2 (0-3) respectively. There was significant difference in median FTND
      score with place of residence (p = 0.03), year of smoking (p = 0.03), age at
      smoking initiation (p = 0.02), smoking pack year (p < 0.001) and consumption of
      smokeless products (p < 0.05). Similarly, there was also significant difference
      in median HSI score with year of smoking (p = 0.002), age of smoking initiation
      (p < 0.001), smoking pack year (p < 0.001), and consumption of smokeless products
      (p < 0.05). As per FTND test score, two in ten current smokers had high nicotine
      dependence (FTND > 6), and HSI scored that three in ten current smokers had high
      nicotine dependence (HSI > 3). CONCLUSION: Our finding revealed that nicotine
      dependence is prevalent among Nepalese smoking population. Further studies are
      required for assurance of tools through bio-markers. Next, smoking cessation
      program need to be developed considering level of nicotine dependence and pattern
      of tobacco use.

PMID- 26309429
TI  - Radiographic study of the problems and failures of endodontic treatment.
AB  - OBJECTIVES: The aim of the present study was to determine radiographically the
      different reasons and problems of endodontic treatment failure. METHODS: The
      periapical radiographs of 100 patients with one hundred teeth (130 root canals)
      were examined to identify the problems and failures of endodontic treatment. The
      various reasons of failure that is under filling, poor filling, over filling and
      presence of procedural errors were recorded for each root filled canal. Chi
      square test was used to determine statistical significance between different
      parameters. RESULTS: Under fillings were found in 46.9% of the root canals. The
      percentage of poor fillings and over fillings were 28.5% and 13% respectively.
      Separated instruments and strip perforations were present in 4% and 3% of the
      teeth, while the presence of furcal perforation and coronal leakage was observed
      in one case each (1%).Endodontic problems and failures were most commonly
      observed in molars compare to anterior and premolar teeth. Mesiobuccal,
      mesiolingual and distobuccal root canals were the most frequently canals with
      endodontic problems and failures. The relationship between mesiobuccal,
      mesiolingual and distal canals in mandibular molars and mesiobuccal, distobuccal
      and palatal canals in maxillary molars in terms of endodontic failures were
      statistically significant by chi square analysis (P<=0.05). CONCLUSION: The most
      common cause of endodontic treatment failure was under filling followed by poor
      filling and over filling and first molar was the most frequently involved tooth
      with endodontic problems and failures.

PMID- 26309430
TI  - Prevalence and Predictors of Depression among Type 2 Diabetes Mellitus
      Outpatients in Eastern Province, Saudi Arabia.
AB  - BACKGROUND: Diabetes Mellitus is frequently accompanied by serious complications.
      Less known is the increased risk for depression. Undiagnosed depression prevents
      initiation of treatment, thereby contributing to poor clinical outcomes.
      OBJECTIVES: Study aimed to determine prevalence and predictors of depression
      among type 2 diabetes mellitus patients. METHODOLOGY: Study was cross-sectional.
      It was conducted in the outpatient clinics of diabetes mellitus in a governmental
      hospital in Eastern Province, Saudi Arabia in 2013. Patients with type 2 diabetes
      mellitus (260 participants) were selected using systematic random sampling
      technique. One interview questionnaire was designed to collect demographic and
      health factors. Two self- administered instruments were used to assess perceived
      social support and depression. Assessment of the relationship between depression
      and its predictors was done using Univariate analysis. Multivariable analysis was
      used to evaluate the combined effect of several factors associated with
      depression among type 2 diabetes mellitus patients after adjusting for
      confounding variables. RESULTS: Almost fifty percent of diabetics were depressed
      (49.6%). Patients with poor diabetes mellitus control (OR 3.221, P.000) and
      unmarried (OR 3.206, P .025) were more risky for developing depression and
      difference was significant. CONCLUSION: Prevalence of depression among Type 2
      diabetes mellitus patients was almost fifty percent. So, diabetics should be
      regularly examined for signs and symptoms of depression.

PMID- 26309431
TI  - Relation of Osteoprotegerin, Visfatin and Ghrelin to Metabolic Syndrome in Type 2
      Diabetic Patients.
AB  - BACKGROUND: It is now realized that insulin resistance plays a principal role in
      initiating the pathologic manifestations of the metabolic syndrome (MetS).
      OBJECTIVES: The aim of this study was to assess the possible role of
      osteoprotegerin, visfatin and ghrelin in the pathogenesis of MetS among type 2
      diabetes mellitus (T2DM). DESIGN AND METHODS: Serum blood samples were obtained
      from 116 subjects (39 T2DM; 48 T2DM with MetS; 29 healthy controls). Glycemic
      status and lipid profile were assessed by enzymatic method. Osteoprotegerin,
      visfatin, ghrelin and insulin were measured by ELISA method. RESULTS:
      Osteoprotegerin and visfatin were significantly higher, while ghrelin was
      significantly lower in diabetic patients compared to healthy control group
      (p<0.05). Moreover, Osteoprotegerin and visfatin showed significant higher levels
      in T2DM patients with MetS than those without MetS (p<0.05). The best cut-off
      values for the investigated markers were determined by ROC curve. Osteoprotegerin
      (1.06 ng/mL), visfatin (32.27 ng/mL) and ghrelin (33.65 pg/mL) presented
      sensitivity of 76%, 92% and 39.1%; respectively and specificity of 41%, 69.2% and
      62.9%; respectively, in predicting MetS among T2DM. Among the investigated
      parameters, Visfatin was the one which predicts MetS among diabetic patients
      [AUC=0.88, p<0.05]. CONCLUSION: Osteoprotegerin, visfatin and ghrelin might be
      implicated in the pathogenesis of diabetes. Moreover, osteoprotegerin and
      visfatin may have additional potential role in the development of the metabolic
      syndrome. Visfatin was superior among studied parameters in predicting MetS among
      T2DM.

PMID- 26309432
TI  - Acute pancreatitis. A more common and severe complication of gallstones in males.
AB  - OBJECTIVE: To describe an increased incidence and severity of gallstone
      pancreatitis in males compared to females. DESIGN METHODS: This is a
      retrospective observational comparative study conducted at Liaquat University of
      Medical and Health Sciences, Jamshoro, Pakistan, over 3 years from June 2008 to
      June 2011. The study includes two hundred and thirty seven (237) patients with a
      mean age of 52.38, Std 13.311,65 (22-87) with 157 (66.24%) females and 80
      (33.75%) males who were admitted as acute abdominal pain secondary to gallstones.
      The patients were mostly diagnosed on ultrasonography and enzyme studies.
      Demographics and other variables are studied and statistical analysis done on
      SPSS version 20. RESULTS: More frequent cases of severe acute pancreatitis were
      observed in males with gallstones (70%) compared to females (P<0.001). The aged
      people had a high prevalence while males were more likely to develop local and
      systemic complications. Severity stratification was done based on different
      criteria's like Ranson's criteria, and APACHEII. Overall mortality was 7.59%.
      Mortality among males was significantly high (70%, n=16) in our study due to an
      increased incidence of fulminant course of the disease. CONCLUSION: Contrary to
      the belief, gallstone associated acute pancreatitis is getting more common in our
      society and especially so in male population.

PMID- 26309433
TI  - Problem based learning (PBL) vs. Case based curriculum in clinical clerkship,
      Internal Medicine innovated Curriculum, Student prospective.
AB  - BACKGROUND: The vast majority of PBL experience is in basic science courses.
      Application of classic Problem based learning in clerkship phase is challenging.
      Although the clinical case is considered a problem, yet solving this problem
      following the burrow's law has faced hurdles. The difficulties are facing the
      learner, the teacher and curricula. We implement innovative curriculum for the
      clerkship year in internal medicine course. METHOD: We surveyed the student just
      before coming to an internal medicine course to ask them about continuing PBL or
      other types of learning in clinical years. A committee was created to study the
      possible ways to integrate PBL in the course. After multiple brainstorming
      meeting, an innovated curriculum was implemented. Student surveyed again after
      they completed their course. The survey is asking them about what is the effect
      of the implemented curriculum in their skills, attitude, and knowledge. RESULTS:
      70% of Students, who finished their basic science in PBL, preferred not to have
      classical PBL, but more a clinical oriented case based curriculum in the clinical
      years. After this innovated curriculum, 50-60 % of students who completed it
      showed a positive response in all aspects of effects including skill, attitude,
      and knowledge. The Innovated curriculum includes daily morning report, 3 bedside
      teaching, investigation session, and clinical reasoning weekly, and Lectures up
      to twice a week. CONCLUSION: We suggest implementing a curriculum with PBL and
      case-based criteria in clinical phase are feasible, we are providing a framework
      with this innovated curriculum.

PMID- 26309434
TI  - The development of a composite bone model for training on placement of dental
      implants.
AB  - OBJECTIVES: It takes a lot of training on patients for both undergraduate to
      develop clinical sense as regards to the placement of dental implants in the jaw
      bones, also, the models provided by the dental implant companies for training are
      usually made of strengthened synthetic foams, which are far from the composition,
      and tactile sense provided by natural bone during drilling for clinical placement
      of dental implants. METHODOLOGY: This is an in-vitro experimental study which
      utilized bovine femur bone, where the shaft of the femur provided the surface
      compact layer, and the head provided the cancellous bone layer, to provide a
      training model similar to jaw bones macroscopic anatomy. Both the compact and
      cancellous bone samples were characterized using mechanical compressive testing.
      RESULTS: The elastic moduli of the cancellous and cortical femur bone were
      comparable to those of the human mandible, and the prepared training model
      provided a more lifelike condition during the drilling and placement of dental
      implants. CONCLUSION: The composite bone model developed simulated the
      macroscopic anatomy of the jaw bones having a surface layer of compact bone, and
      a core of cancellous bone, and provided a better and a more natural hands-on
      experience for placement of dental implants as compared to plastic models made of
      polyurethane.

PMID- 26309435
TI  - Patients' Satisfaction with Primary Health Care Centers' Services, Majmaah,
      Kingdom of Saudi of Saudi Arabia.
AB  - BACKGROUND: PHC Patient' satisfaction represents a key marker for the quality of
      health care delivery and this internationally accepted factor needs to be studied
      repeatedly for smooth functioning of the health care systems. The objectives of
      the current study were to determine the level of patients' satisfaction with the
      primary health care services provided in Majmaah city, Kingdom of Saudi Arabia;
      to identify the reasons behind satisfaction or dissatisfaction and to determine
      the effect of the social factors on the level of satisfaction. METHODOLOGY: The
      study was a cross-sectional facility- based. The sample comprised 370 patients
      selected by stratified and systematic sampling at the health centers' level and
      the patients' level respectively. The data were collected by a pre-tested
      questionnaire and analyzed by SPSS software. RESULTS: Patients' level of
      satisfaction was 82%. The reasons behind satisfaction were cleanliness of the
      facilities and technical competencies of the staff (33.1% and 24.2%). The study
      showed that the most stated reason behind dissatisfaction was the unsuitable
      buildings (29%). Significant association was found between the level of patients'
      satisfaction about PHC centers services and the respondents' level of education.
      CONCLUSION: The level of satisfaction with the services provided by PHC centers
      in Majmaah is high. The gender, marital status and income have no effect on the
      level of satisfaction with the services provided by PHC centers. However, the
      lower educated are more satisfied than the higher educated. Cleanliness,
      competence of the staff along with respect and good handling are the drivers
      behind the high level of satisfaction.

PMID- 26309436
TI  - Study of Serum Hepcidin as a Potential Mediator of the Disrupted Iron Metabolism
      in Obese Adolescents.
AB  - BACKGROUND & AIMS: The prevalence of obesity continues to rise in both developed
      and developing nations. An association between iron status and obesity has been
      described in children and adults. We aimed to study the relation between serum
      hepcidin level and both iron as well as high sensitive CRP status in obese
      adolescents. MATERIALS & METHODS: This work was conducted on 80 adolescents aging
      12-14 years old, divided into two equal groups; obese and non-obese.
      Anthropometric measurements, determination of haemoglobin, serum iron, total iron
      binding capacity (TIBC), transferrin saturation, serum ferritin, soluble serum
      transferrin receptor (sTfR), high sensitive CRP (hs -CRP) and serum hepcidin were
      performed. RESULTS: Obese adolescents showed significantly lower levels of
      haemoglobin, serum iron, serum ferritin and transferrin saturation. Significant
      higher diastolic blood pressure, higher mean TIBC, sTfR, serum hepcidin and hs 
      CRP were also found. Serum hepcidin level correlated positively with BMI and hs-
      CRP, but negatively with iron level in obese group. CONCLUSION: These data
      suggest that hepcidin is an important modulator of anemia in obese patients.
      Obesity can be considered as a low grade inflammatory state, that stimulates the
      production of inflammatory markers such as CRP which can up-regulate hepcidin
      synthesis.

PMID- 26309437
TI  - Spontaneous recovery of post-traumatic cerebrospinal fluid rhinorrhea following
      meningitis: A case report.
AB  - The aim of the present report was to present the patient with an anterior cranial
      base fracture who developed post-traumatic cerebrospinal fluid rhinorrhea, which
      recovered after onset of meningitis complication. A 26-year-old male patient who
      had a traffic accident one week ago was sent to our clinic because of his
      rhinorrhea persisting for 4 days. On cranial computed tomography, fracture of the
      left frontal skull base and sinus walls, a fracture line on temporal bone,
      parenchymal bleeding in the vicinity of the frontal sinus, subarachnoidal
      bleeding and left temporal extradural hematoma were detected. Then he underwent
      sinus wall repair and extradural hematoma was drained through bifrontal
      craniotomy. However, rhinorrhea persisted which resulted a deterioration in
      consciousness and he entered into a deep somnolent state. When his symptoms of
      meningitis became apparent, rhinorrhea of the patient disappeared. The patient
      transferred in intensive care unit and re-connected to a lumbar drainage system.
      On cerebral magnetic resonance imaging, regression of contrast-enhanced lesions
      localized in the left anterotemporal and frontal and in the regions lateral to
      the right trigon and medial to the right thalamus and in the right
      posteroparietal regions was observed. Despite repair of the anterior cranial
      fracture and lumbar drainage, rhinorrhea may persist. Herein, development of
      meningitis caused disappearing of rhinorrhea symptoms without any need for
      surgical intervention. 

PMID- 26309438
TI  - Low flow venous malformation lesion presented with medial canthal swelling
      simulating swelling of the lacrimal sac origin: A case report.
AB  - Low flow venous malformation lesions (e.g. cavernous venous malformations) are
      commonly seen in the orbit and peri-orbital area. Common conditions may present
      with unexpected presentation. Here we report a 50 years old male patient with low
      flow venous malformation lesion presented with medial canthal swelling similar to
      the swelling typically seen in lacrimal sac related pathologies. 

PMID- 26309439
TI  - Pseudotumor Cerebriasa Rare Side Effect of Intrathecal Cytarabine.
AB  - Pseudotumorcerebri (PTC), also known as idiopathic increase in intracranial
      pressure, is associated with several conditions and as a side effect of many
      medications. We are reporting a case of a PTC caused by intrathecal cytarabine as
      a rare side effect of this medication. 

PMID- 26309440
TI  - Celiac Disease in an Adoptive Child with Recurrent Giardia Infection.
AB  - Celiac disease (CD) is an inflammatory disease of the small intestine. A complete
      management and differential diagnosis of such disease includes food intolerances,
      intestinal infections, and irritable bowel syndrome. We describe an 8-years-old
      adoptive girl from Congo with negative medical history. Patient followed for
      recurrent abdominal pain and diarrhea associated to Giardia infection,
      unresponsive to antiparasitic therapy. Persistence of symptoms despite
      antiparasitic therapy, prompted us to perform: 1- Blood screening of Celiac
      disease, which was negative; 2- Genetic evaluation of celiac disease, which
      revealed the presence of HLA-DQ2 heterodimer; and 3- Esophagogastroduodenoscopy,
      which showed duodenal villous atrophy and crypt hyperplasia, associated with
      Helicobacter Pylori infection. The child was treated in accordance with
      international recommendations using a Gluten-free diet and specific antibiotics,
      which lead to the resolution of the symptoms. Our patient's clinical history
      seems peculiar, considering that, recurrent Giardiasis may mimic the symptoms of
      Celiac disease and may simulate clinical and histological picture of active
      Celiac disease. Early diagnosis may help prevent the complications of untreated
      celiac disease. 

PMID- 26309441
TI  - Inflammatory Myofibroblastic Tumor Arising in the External Ear: Unexpected
      Location. (Case Report).
AB  - We present an unexpected extremely rare case of an inflammatory myofibroblastic
      tumor (IMT) of the external ear. A 3-year-old boy presented with a mass arising
      on the posterior aspect of the left ear lobule and extending to the external
      auditory canal. This mass grew slowly and showed no skin changes. Radiologically,
      it was diagnosed as a vascular tumor. Surgical excision and primary closure was
      performed for the patient. Histopathologic examination demonstrated a
      circumscribed noncapsulated mass formed by a proliferation of spindle cells in
      deep dermis and subcutaneous tissue. The spindle cells were mixed with
      lymphoplasmacytic infiltration compatible with the IMT. Because it is very rare
      to arise in this location, we present this case as a case report with details
      histopathological examination and reviewed the English literature for similar
      cases. 

PMID- 26309443
TI  - Extended use of cardiopulmonary bypass in a multidisciplinary hospital.
AB  - OBJECTIVE: To share our experience highlighting the additional use of
      cardiopulmonary bypass (CPB) in cases other than the conventional ischemic,
      congenital and valvular heart diseases. METHODOLOGY: All patients undergoing non
      traditional cardiac surgery utilizing the cardiopulmonary bypass during a period
      from 1999 to 2009 reviewed. Their preoperative presentation, operative strategy
      and immediate postoperative status were assessed. RESULTS: A total of six such
      cases were identified including three female and three male patients. Two
      patients presented with road traffic accident having aortic transection along
      with other injuries. They underwent repair utilizing partial cardiopulmonary
      bypass. One patient presented with large PDA aneurysm and symptoms related to its
      pressure effect on respiratory system. He underwent repair under hypothermic
      circulatory arrest. These three patients were done via left thoracotomy. Three
      patients underwent deep hypothermic circulatory arrest, one for removal of
      thrombus from right atrium after complicated liver abscess, one patient required
      vascular graft interposition in left internal carotid artery for aneurysm
      extending into cranium and the third one underwent resection of vascular tumor of
      posterior cranial fossa. One patient required exploration for bleeding. One
      patient died after prolonged hospitalization. Rest of the patient had
      unremarkable postoperative course and were discharged home. CONCLUSION: Our short
      experience highlights the extended use of cardiopulmonary bypass in a
      multidisciplinary hospital, facilitating to perform complex, technically
      challenging non cardiac procedures which otherwise may not be possible.

PMID- 26309442
TI  - Ameliorating Role Exerted by Al-Hijamah in Autoimmune Diseases: Effect on Serum
      Autoantibodies and Inflammatory Mediators.
AB  - Autoimmune diseases have common properties characterized by abnormal blood
      chemistry with high serum autoimmune antibodies, and inflammatory mediators.
      Those causative pathological substances (CPS) cannot be excreted by physiological
      mechanisms. Current treatments for autoimmune diseases involve steroids,
      cytotoxic drugs, plasmapheresis and monoclonal antibodies. Wet cupping therapy
      (WCT) of prophetic medicine is called Al-hijamah that treats numerous diseases
      having different etiology and pathogenesis via a pressure-dependent and size
      dependent non-specific filtration then excretion of CPS causing clearance of
      blood and interstitial fluids. Al-hijamah clears blood passing through the
      fenestrated skin capillaries. Medical bases of Al-hijamah were reported in the
      evidence-based Taibah mechanism (Taibah theory). Al-hijamah was reported to be an
      excellent treatment for rheumatoid arthritis that improved patients' blood
      chemistry and induced significant clinical improvement and pharmacological
      potentiation. Al-hijamah improved the natural immunity and suppressed the
      pathological immunity through decreasing the serum level of autoantibodies,
      inflammatory mediators, and serum ferritin (a key player in autoimmunity). Al
      hijamah reduced significantly pain severity, number of swollen joints and disease
      activity with no significant side effects. Main steps of Al-hijamah are skin
      suction (cupping), scarification (sharatmihjam in Arabic) and second suction
      (triple S technique) that is better therapeutically than the traditional WCT
      (double S technique). Whenever an excess noxious substance is to be removed from
      patients' blood and interstitial fluids, Al-hijamah is indicated. Shartatmihjam
      is a curative treatment in prophetic teachings according to the prophetic
      hadeeth: "Cure is in three: in shartatmihjam, oral honey and cauterization. I do
      not recommend my nation to cauterize". Al-hijamah may have better therapeutic
      benefits than plasmapheresis. Al-hijamah may be promising in treating autoimmune
      diseases as a sole treatment or adjuvant treatment. 

PMID- 26309444
TI  - Snakes and snakebite envenoming in Northern Tanzania: a neglected tropical health
      problem.
AB  - BACKGROUND: Snakebites cause considerable human and livestock injuries as well as
      deaths worldwide, and particularly have a high impact in sub-Saharan Africa.
      Generating a basic platform of information on the characteristics of snakes and
      snakebites in various countries is relevant for designing and implementing public
      health interventions. METHODS: This study was performed to identify types of
      snakes and some of the characteristics of snakebite cases in two communities, an
      agricultural and a pastoralist, in Arusha region, northern Tanzania. A total of
      30 field visits were carried out in areas considered by local inhabitants to be
      potential microhabitats for snakes. Direct observation of snake types based on
      morphological features and a structured questionnaire were employed for data
      collection. RESULTS: A total of 25 live and 14 dead snakes were encountered.
      Among the dead ones, the following species were identified: two black-necked
      spitting cobras (Naja nigricollis); five puff adders (Bitis arietans), one common
      egg-eater (Dasypeltis scabra); two rufous-beaked snakes (Ramphiophis rostratus);
      two brown house snakes (Lamprophis fuliginosus); one Kenyan sand boa (Eryx
      colubrinus), and one black mamba (Dendroaspis polylepis). The frequency of snake
      encounters was significantly higher (chi (2) = 4.6; p = 0.03) in the pastoral
      than in the agricultural area; there were more snakebite cases in the former, but
      the differences were not statistically significant (p = 0.7). A total of 242
      snakebite victims attended at the Meserani Clinic, located in the study area,
      between the years 2007 to 2012. Of all cases, 146 (61.6 %) and 96 (38.4 %) were
      male and female patients, respectively. As for age distribution, 59.1 % of
      snakebite victims were from the economically active age groups between 15 and 55
      years. CONCLUSION: Snakebites are a threat to rural communities and public health
      in general. The burden of snakebites in Tanzania presents an epidemiologically
      similar picture to other tropical countries. Livestock keeping and agriculture
      are the major economic activities associated with snakebites. Community-based
      public education is required to create awareness on venomous snakes and
      predisposing factors to snakebites. These tasks demand integration of diverse
      stakeholders to achieve a common goal of reducing the impact of human suffering
      from these envenomings in Tanzania.

PMID- 26309445
TI  - Liver trauma: WSES position paper.
AB  - The liver is the most injured organ in abdominal trauma. Road traffic crashes and
      antisocial, violent behavior account for the majority of liver injuries. The
      present position paper represents the position of the World Society of Emergency
      Surgery (WSES) about the management of liver injuries. 

PMID- 26309446
TI  - A Preliminary Study of Self-Reported Food Selectivity in Adolescents and Young
      Adults with Autism Spectrum Disorder.
AB  - Although it is well-established that picky eating is a common feature of early
      development in autism spectrum disorder (ASD), far less is known about food
      selectivity during adolescence and adulthood. Using portions of the
      Adult/Adolescent Sensory Profile, food selectivity self-ratings were obtained
      from 65 high-functioning adolescents/young adults with ASD and compared to those
      of 59 typically developing controls matched on age, IQ, and sex ratio.
      Individuals with ASD reported preferring familiar foods (food neophobia) and
      disliking foods with particular textures and strong flavors. Providing linkage to
      everyday behavior, parent ratings of daily living skills were lower among
      individuals with ASD and food neophobia than among those without food neophobia.
      Food selectivity continues to be an important issue for adolescents/young adults
      with ASD.

PMID- 26309448
TI  - Long-term functional and radiographic outcomes in 243 operated ankle fractures.
AB  - BACKGROUND: Large comparative studies that have evaluated long-term functional
      outcome of operatively treated ankle fractures are lacking. This study was
      performed to analyse the influence of several combinations of malleolar fractures
      on long-term functional outcome and development of osteoarthritis. METHODS:
      Retrospective cohort-study on operated (1995-2007) malleolar fractures. Results
      were assessed with use of the AAOS- and AOFAS-questionnaires, VAS-pain score,
      dorsiflexion restriction (range of motion) and osteoarthritis. Categorisation was
      determined using the number of malleoli involved. RESULTS: 243 participants with
      a mean follow-up of 9.6 years were included. Significant differences for all
      outcomes were found between unimalleolar (isolated fibular) and bimalleolar (a
      combination of fibular and medial) fractures (AOFAS 97 vs 91, p = 0.035; AAOS 97
      vs 90, p = 0.026; dorsiflexion restriction 2.8 degrees  vs 6.7 degrees , p =
      0.003). Outcomes after fibular fractures with an additional posterior fragment
      were similar to isolated fibular fractures. However, significant differences were
      found between unimalleolar and trimalleolar (a combination of lateral, medial and
      posterior) fractures (AOFAS 97 vs 88, p < 0.001; AAOS 97 vs 90, p = 0.003; VAS
      pain 1.1 vs 2.3 p < 0.001; dorsiflexion restriction 2.9 degrees  vs 6.9 degrees ,
      p < 0.001). There was no significant difference in isolated fibular fractures
      with or without additional deltoid ligament injury. In addition, no functional
      differences were found between bimalleolar and trimalleolar fractures.
      Surprisingly, poor outcomes were found for isolated medial malleolar fractures.
      Development of osteoarthritis occurred mainly in trimalleolar fractures with a
      posterior fragment larger than 5 %. CONCLUSIONS: The results of our study show
      that long-term functional outcome is strongly associated to medial malleolar
      fractures, isolated or as part of bi- or trimalleolar fractures. More cases of
      osteoarthritis are found in trimalleolar fractures.

PMID- 26309447
TI  - Synergic effect of GSTP1 and blood manganese concentrations in Autism Spectrum
      Disorder.
AB  - We used data from 100 age- and sex-matched case-control pairs (age 2-8 years)
      from Jamaica to investigate whether there is an interaction between glutathione-S
      transferase (GST) genes and blood manganese concentrations (BMC) in relation to
      Autism Spectrum Disorder (ASD). Our findings, indicate that among children who
      had the Ile/Ile genotype for GST pi 1 (GSTP1), those with BMC >= 12ug/L had about
      4 times higher odds of ASD than those with BMC < 12ug/L, (P=0.03) under a co
      dominant genetic model. After adjusting for potential confounders, among the
      subgroup of children with genotype Ile/Ile, those with BMC >= 12ug/L had about
      six times higher odds of ASD than those with BMC < 12ug/L, (P=0.04). The results
      were similar when a recessive genetic model was used. These findings suggest a
      possible synergic effect of BMC and GSTP1 in ASD. Since our analysis included a
      variety of genetic models and was not adjusted for multiple testing, replication
      in other populations is warranted.

PMID- 26309449
TI  - Renal Cysts and Nephrocalcinosis in a Patient Deficient in 11 beta-Hydroxylase
      Enzyme.
AB  - BACKGROUND: Chronic hypokalemia is known to induce renal structural and
      functional abnormality. The former includes induction of renal cyst formation and
      interstitial fibrosis while the latter entails urine-concentrating defect.
      However, these hypokalemia-mediated changes occur in a handful of conditions
      including primary aldosteronism, distal renal tubular acidosis, Liddle's disease,
      apparent mineralocorticoid excess syndrome and Bartter's type 3 syndrome. Such a
      finding has never been described in an 11 beta-hydroxylase deficient individual.
      CASE REPORT: We describe a case of a 15-year-old male, deficient in 11 beta
      hydroxylase enzyme, presenting with hypertensive haemorrhage in basal ganglia and
      chronic hypokalemia-mediated nephrocalcinosis and renal cysts. To add to the
      uniqueness, our patient was discovered to harbour bilateral testicular adrenal
      rests as well. CONCLUSIONS: An early diagnosis could help prevent these sequelae
      and preserve long-term renal function and safeguard against ill-effects of
      hypertension. Besides, aetiology of nephrocalcinosis should be sought for and
      corrected.

PMID- 26309450
TI  - Massive Upper Gastrointestinal Bleeding from a Splenic Artery Pseudoaneurysm
      Caused by a Penetrating Gastric Ulcer: Case Report and Review of Literature.
AB  - BACKGROUND: Splenic artery aneurysm and pseudoaneurysm are rare pathologies. True
      aneurysms are usually asymptomatic. Aneurysm rupture occurring in 2-3% of cases
      results in bleeding into the lesser sack, peritoneal space or adjacent organs
      typically presenting as abdominal pain and hemodynamic instability. In contrast,
      pseudoaneurysms are nearly always symptomatic carrying a high risk of rupture of
      37-47% and mortality rate of 90% if untreated. Therefore, prompt diagnosis and
      treatment are essential in the management of patients with splenic artery
      pseudoaneurysm. Typical causes include pancreatitis and trauma. Rarely, the
      rupture of a pseudoaneurysm presents as upper gastrointestinal (UGI) bleeding.
      Among causes, peptic ulcer is the casuistic one. CASE REPORT: This report
      describes a very rare case of recurrent UGI bleeding from a splenic artery
      pseudoaneurysm caused by a penetrating gastric ulcer. After negative results of
      endoscopy and ultrasound, the diagnosis was established in CT angiography. The
      successful treatment consisted of surgical ligation of the bleeding vessel and
      suture of the ulcer with preservation of the spleen and pancreas, which is rarely
      tried in such situations. CONCLUSIONS: The most important factor in identifying a
      ruptured splenic artery pseudoaneurysm as a source of GI bleeding is considering
      the diagnosis. UGI hemorrhage from splenic artery pseudoaneurysm can have a
      relapsing course providing false negative results of endoscopy and ultrasound if
      performed between episodes of active bleeding. In such cases, immediate CT
      angiography is useful in establishing diagnosis and in application of proper
      therapy before possible recurrence.

PMID- 26309451
TI  - High-resolution multi-photon imaging of morphological structures of
      caenorhabditis elegans.
AB  - In this protocol, we combine two-photon excitation fluorescence to visualize in
      caenorhabditis elegans (C. elegans) dopaminergic (DAergic) neurons and their
      processes with non-linear optical measurements to reconstruct the three
      dimensional architecture of the pharyngeal region and the muscular system of the
      anterior and mid-body region. Femto second laser pulses excite second-harmonic
      generation (SHG) and third harmonic generation (THG) signals, which show detailed
      structural information regarding the organization of myofibrils that are arranged
      around the central pharynx region. The combination of two-photon excitation with
      SHG and THG imaging is a very powerful tool to study cell morphology, the
      microarchitecture and tissue arrangement in C. elegans.

PMID- 26309452
TI  - Quantification of Glutathione in Caenorhabditis elegans.
AB  - Glutathione (GSH) is the most abundant intracellular thiol with diverse functions
      from redox signaling, xenobiotic detoxification, and apoptosis. The
      quantification of GSH is an important measure for redox capacity and oxidative
      stress. This protocol quantifies total GSH from Caenorhabditis elegans, an
      emerging model organism for toxicology studies. GSH is measured using the 5,5'
      dithiobis-(2-nitrobenzoic acid) (DTNB) cycling method originally created for cell
      and tissue samples but optimized for whole worm extracts. DTNB reacts with GSH to
      from a 5'-thio-2-nitrobenzoic acid (TNB) chromophore with maximum absorbance of
      412 nm. This method is both rapid and sensitive, making it ideal for studies
      involving a large number of transgenic nematode strains. 

PMID- 26309453
TI  - [Rare association: Sjogren Syndrome and liposarcoma of the parotid].

PMID- 26309454
TI  - [Delayed cerebellar hemorrhage after burr hole drainage of a chronic subdural
      hematoma].

PMID- 26309455
TI  - Patient perceptions about laparoscopy at Komfo Anokye Teaching Hospital, Ghana.
AB  - INTRODUCTION: Laparoscopy has become the gold standard for many surgical cases in
      the developed world. It however, remains a rarity in developing countries for
      several reasons, a major one being cost. This study aimed to determine the
      knowledge and attitude of patients attending Komfo Anokye Teaching Hospital
      (KATH) in Kumasi, Ghana toward laparoscopic surgery and their willingness to pay
      for it. METHODS: A cross-sectional survey was conducted among patients attending
      specialist clinics at KATH. RESULTS: 1070 patients participated. Mean age was
      40+/-15 years. 54% were city-dwellers. 14% had salary-paying jobs. None had
      undergone prior laparoscopic surgery. 3% had knowledge of laparoscopy. 95%
      preferred laparoscopy to open surgery mainly because of faster recovery and less
      post-op pain. Age >45 years (AOR = 0.53, p = 0.03) and higher education (AOR =
      2.00, p = 0.04) were significant predictors of patient choice. Among those
      preferring laparoscopy, 78% were willing to pay more than the baseline cost of
      open surgery for laparoscopy. A history of previous abdominal surgery (AOR =
      0.67, p = 0.02), having a salaried job compared with being unemployed (AOR =
      2.36, p < 0.01) and living in the city compared with the village (AOR = 1.78, p =
      0.04) were significant predictors of patients' willingness to pay more for
      laparoscopy. CONCLUSION: Knowledge about laparoscopy and its benefits are
      severely lacking among patients at KATH. Once educated about its benefits, most
      people prefer laparoscopy even if they needed to pay more for it even in resource
      limited countries like Ghana.

PMID- 26309456
TI  - An audit of request forms submitted in a multidisciplinary diagnostic center in
      Lagos.
AB  - INTRODUCTION: Request forms are important means of communication between
      physicians and diagnostic service providers. Pre-analytical errors account for
      over two thirds of errors encountered in diagnostic service provision. The
      importance of adequate completion of request forms is usually underestimated by
      physicians which may result in medical errors or delay in instituting appropriate
      treatment. The aim of this study was to audit the level of completion of request
      forms presented at a multidisciplinary diagnostic center. METHODS: A review of
      all requests forms for investigations which included radiologic, laboratory and
      cardiac investigations received between July and December 2011 was performed to
      assess their level of completeness. The data was entered into a spreadsheet and
      analyzed. RESULTS: Only 1.3% of the 7,841 request forms reviewed were fully
      completed. Patient's names, the referring physician's name and gender were the
      most completed information on the forms evaluated with 99.0%, 99.0% and 90.3%
      completion respectively. Patient's age was provided in 68.0%, request date in
      88.2%, and clinical notes/ diagnosis in 65.9% of the requests. Patient's full
      address was provided in only 5.6% of requests evaluated. CONCLUSION: This study
      shows that investigation request forms are inadequately filled by physicians in
      our environment. Continuous medical education of physicians on the need for
      adequate completion of request forms is needed.

PMID- 26309457
TI  - An observational study of hypertension treatment and patient outcomes in a
      primary care setting.
AB  - INTRODUCTION: Evaluation and treatment of high blood pressure are vital to
      reducing hypertension-related morbidity. There are limited data on treatment of
      hypertension in Lesotho. The aim of this study was to investigate hypertension
      treatment and control in a primary care setting in Lesotho. METHODS: A cross
      sectional study was conducted among hypertensive patients treated at Domiciliary
      Health Clinic in Maseru, Lesotho between April and May 2013. We reviewed medical
      records and evaluated hypertension treatment and blood pressure control in the
      past 12 months. Patients were interviewed to assess adherence to hypertension
      treatment. Logistic regression analysis was used to identify factors associated
      with poor blood pressure control. RESULTS: 70 patients were enrolled in the
      study; 90.0% were female, the mean age was 57.7 years, 80.0% were
      overweight/obese and 27.1% had diabetes mellitus. 90.0% of the patients received
      combination antihypertensive therapy; the most frequently prescribed drugs were
      hydrochlorothiazide (90.0%), captopril (67.1%) and atenolol (51.4%). The majority
      of the patients had chronic uncontrolled hypertension. 67.2% of the patients had
      continuous access to antihypertensive drugs in the past 12 months; adherence to
      medication, diet and exercise was 64.3%, 37.1% and 7.1% respectively. Age >=65
      was the strongest independent predictor of poor blood pressure control (AOR =
      10.3, 95% CI: 1.21-88.98, p = 0.033). CONCLUSION: There is a need for
      interventions to improve hypertension care and outcomes in this setting. Efforts
      should be made to improve assessment of hypertensive patients, optimise
      antihypertensive therapy and promote patient adherence to treatment.

PMID- 26309458
TI  - [Nephrocalcinosis complicating miliary tuberculosis in an infant].

PMID- 26309460
TI  - [Waardenburg syndrome].

PMID- 26309459
TI  - A case of subarachnoid hemorrhage revealed by an acute coronary syndrome (ACS).
AB  - The subarachnoid hemorrhage (SAH) is definitely the best descriptive model of the
      interaction between cardiovascular system and cerebral damage. The underlying
      mechanism of cardiovascular alterations after SAH is linked to the adrenergic
      discharge related to aneurysm rupture. Cardiac and pulmonary complications are
      common after severe brain injury, especially the aneurismal subarachnoid
      hemorrhage. Acute neurogenic pulmonary edema is not exceptional; it may occur in
      20% of cases and commonly follows a severe subarachnoid hemorrhage. Severe
      myocardial damage with cardiogenic shock may possibly reveal the SAH (3% of
      cases) and mislead to wrong diagnosis of ACS with dramatic therapeutic
      consequences. The contribution of CT and cerebral angiography is essential for
      diagnosis and treatment. Surgical or endovascular treatment depends on location,
      size and shape of the aneurysm, on patient's age, neurological status and
      existence of concomitant diseases. We report the case of a 58 years old patient,
      with a past medical history of diabetes and hypertension, admitted for acute
      pulmonary edema with cardiogenic shock. This case illustrates an unusual
      presentation of aneurismal SAH in a patient presenting with an acute coronary
      syndrome. 

PMID- 26309461
TI  - [Osteochondroma of the femur revealed by an iterative lesion of the vastus
      lateralis: report of a case].

PMID- 26309462
TI  - [Acute pancreatitis revealing a hydatid cyst of the pancreas].

PMID- 26309463
TI  - [Enormous tibial osteosarcoma: about a historical case].

PMID- 26309464
TI  - [Ethmoido-frontal mucocele occurring in type 2 diabetes].

PMID- 26309465
TI  - [Late endophthalmitis complicating filtering surgery: report of a case].

PMID- 26309466
TI  - [Apert syndrome in a 60-year old Congolese: about one observation].

PMID- 26309467
TI  - Closed reduction and intramedullary pinning in the treatment of adult radial neck
      fractures: a case report.
AB  - Closed reduction and intramedullary pinning (CIMP) in pediatric radial neck
      fractureswas first reported by Metaizeau in 1980 andsatisfactory results have
      been published several times. The current literature did not encounter any
      publication related to the implementation of Metaizeau method to adult patients.
      We applied Metaizeau technique to an adult radial neck fracture and we have
      achieved satisfactory results. As this case report is single case of this method
      applied to an adult, we decided to present this case. 

PMID- 26309468
TI  - Extra-uterine twin pregnancy: case report of spontaneous bilateral tubal ectopic
      pregnancy.
AB  - Spontaneous bilateral ectopic pregnancy is the rarest form of ectopic pregnancy.
      Bilateral tubal pregnancies in the absence of preceding induction of ovulation
      are a rare occurrence, with an estimated incidence of 1 in 725 to 1 in 1580
      ectopicpregnancies. They are usually diagnosed at the time of surgery. We report
      a case of spontaneous bilateral tubal pregnancies diagnosed intraoperatively. A
      33-year-old patient was admitted after light vaginal bleeding, 35 days after her
      last menstruation. A bilateral salpingectomy was performed without complication
      and the pathology report confirmed the diagnosis. This is an unusual case of
      early diagnosis. The diagnosis of bilateral tubal pregnancy is usually
      madeintraoperatively. This underscores the importance ofidentifying and closely
      examining both tubes at the time ofsurgery, even in the presence of significant
      adhesive disease. 

PMID- 26309469
TI  - [Ethnobotanical study of plants used in the treatment of diabetes in the
      traditional medicine of Maritime Region, Togo].

PMID- 26309470
TI  - Prevalence of helmet use among motorcycle users in Dar Es Salaam, Tanzania.
AB  - INTRODUCTION: The purpose of this study was to determine prevalence of helmet use
      among motorcyclists as one of the preventive measures for road traffic injuries.
      METHODS: A cross sectional observational survey was conducted in the 3 Districts
      (Kinondoni, Ilala and Temeke) that make Dar es Salaam. Tanzania. A standardized
      line-listing form and checklist were used to record the drivers and passengers
      use of helmet as observed by study investigators. Data for helmet use was
      collected on one weekday and one weekend day. Time for observation was during the
      rush hour in the morning, noon and evening. Then data were entered into Epi Info
      3.5.1 analysis. RESULTS: A total of 7,678 motorcycle drivers and 4,328 passengers
      observed in this study. Drivers were almost male (98.8%) and 73.2% of all
      passengers were males. The prevalence use of helmet use among motorcyclist's
      riders was 82.1% and among passengers was 22.5%. Proportion of helmet use in
      drivers and passengers observed were relatively similar during weekday and
      weekend day and time of observation. CONCLUSION: This study showed the relative
      high helmet use among motorcyclist riders though very low in passengers. This
      study recommends increased community awareness on helmet use among passengers and
      enforcement and revival of road safety laws of passengers and motorcyclists on
      helmet use.

PMID- 26309471
TI  - [Epidemiological profile of end stage renal disease at the Military Hospital in
      Rabat, Morocco].

PMID- 26309472
TI  - Solitary hepatic lymphangioma in an 8-month-old child.

PMID- 26309474
TI  - [A rare case of pure subtalar dislocation].

PMID- 26309473
TI  - [Candida albicans endocarditis complicating Behcet disease].

PMID- 26309475
TI  - [Cystic lymphangioma of the parotid gland].

PMID- 26309476
TI  - [Isolated involvment of the ear during the pemphigus vulgaris].

PMID- 26309477
TI  - A pulmonary aneurysm: don't forget Hughes-Stovin syndrome.

PMID- 26309478
TI  - [Still disease of the adult complicated by fulminant hepatitis].

PMID- 26309479
TI  - Pedunculate leiomyoma of the scrotum.

PMID- 26309480
TI  - [POEMS syndrome: a diagnosis to not to ignore].

PMID- 26309481
TI  - [Chronic ethmoido maxillary sinusitis in a diabetic: think of actinomycosis].

PMID- 26309482
TI  - Field Epidemiology and Laboratory Training Programs have been in Africa for 10
      years, what is their effect on laboratory-based surveillance? Reflections from a
      panel at the African Society of Laboratory Medicine December 2014 Cape Town
      meeting.

PMID- 26309483
TI  - Epidural injection with or without steroid in managing chronic low back and lower
      extremity pain: ameta-analysis of ten randomized controlled trials.
AB  - BACKGROUND: Chronic low back and lower extremity pain is mainly caused by lumbar
      disc herniation (LDH) and radiculitis. Various surgery and nonsurgical
      modalities, including epidural injections, have been used to treat LDH or
      radiculitis. Therefore, we conducted this meta-analysis to assess the effects of
      the two interventions in managing various chronic low and lower extremity pain.
      METHODS: A systematic literature search was conducted to identify randomized
      controlled trials (RCTs) which compared the effect of local anesthetic with or
      without steroids. The outcomes included pain relief, functional improvement,
      opioid intake, and therapeutic procedural characteristics. Pooled estimates were
      calculated using a random-effects or fixed-effects model, depending on the
      heterogeneity between the included studies. RESULTS: 10 RCTs (involving 1111
      patients) were included in this meta-analysis. The pooled results showed that
      41.7% of patients who received local anesthetic with steroid (group 1) and 40.2%
      of patients who received local anesthetic alone (group 2) had significant
      improvement in pain relief. And the Numeric Rating Scale pain scales were
      significantly reduced by 4.09 scores (95% CI: -4.26, -3.91), and 4.12 (95% CI: 
      4.35, -3.89) scores, respectively. Similarly, 39.8% of patients in group 1 and
      40.7% of patients in group 2 achieved significantly improved functional status.
      The Oswestry Disability Index in the two groups were reduced by 14.5 (95% CI: 
      15.24, -13.75) and 12.37 (95% CI: -16.13, -8.62), respectively. The average
      procedures per year in group 1 was 3.68 +/- 1.17 and 3.68 +/- 1.26 in group 2
      with an average total relief per year of 31.67 +/- 13.17 weeks and 32.64 +/-
      13.92 weeks, respectively. The opioid intake decreased from baseline by 8.81 mg
      (95% CI: -12.24, -5.38) and 16.92 mg (95% CI: -22.71, -11.12) in the two groups,
      respectively. CONCLUSION: This meta-analysis confirms that epidural injections of
      local anesthetic with or without steroids have beneficial but similar effects in
      the treatment of patients with chronic low back and lower extremity pain.

PMID- 26309484
TI  - Association of genetic polymorphisms with osteosarcoma risk: a meta-analysis.
AB  - Osteosarcoma (OS) is the most common pediatric and adult bone malignancy
      worldwide. Genetic polymorphisms may play critical roles in the development of
      OS. However, there present inconclusive results. The current study was to
      investigate the role of genetic polymorphisms in OS risk. Electronic databases
      were searched for relevant studies published between 2000 and 2014. The odds
      ratio (OR) with its 95% confidence interval (CI) were employed to estimate the
      associations. Total 7 studies containing 911 OS patients and 1145 matched
      controls were included. Our results found that CTLA-4 +49A/G G allele and TGF
      beta1 29T/C C allele were more frequent in OS patients than that in controls,
      indicating that these two alleles were significantly associated with increased
      the risk of OS (G vs. A: OR = 1.36, 95% CI = 1.13-1.64, P = 0.001; C vs. T: OR =
      1.49, 95% CI = 1.17-1.90, P = 0.001) in a fixed-effect model. This significant
      relationship was also found under other three genetic models in both variants
      (P<0.05). While no association was found between TNF-alpha -308G/A or TNF-beta
      +252A/G polymorphism and OS risk. In conclusion, our results demonstrated that
      CTLA-4 +49A/G and TGF-beta1 29T/C variants were significantly associated with OS
      susceptibility. Although number of included studies is small, several
      polymorphisms appearing to significantly influence the OS risk should be focused.
      Moreover, further studies with gene-gene and gene-environmental interactions
      should be considered. 

PMID- 26309485
TI  - Rehabilitation protocol after arthroscopic rotator cuff repair: early versus
      delayed motion.
AB  - PURPOSE: To evaluate the effectiveness of early and delayed motion in
      rehabilitation after arthroscopic rotator cuff repair using a meta-analysis from
      randomized controlled trials. MATERIALS AND METHODS: Electronic searches of the
      CENTRAL, PUBMED, and EMBASE were used to identify randomized controlled trials
      that evaluated the effectiveness and safety of early and delayed motion for
      rehabilitation after arthroscopic rotator cuff repair. The methodological quality
      of the studies was assessed by the Cochrane Collaboration tool for assessing risk
      of bias. RESULTS: Four randomized controlled trials involving a total of 348
      shoulders were included. Of these, two were rated as high quality and two were
      rated as moderate quality. No significant publication bias was detected by
      Egger's test and sensitivity analysis demonstrates a statistically robust result.
      Our meta-analysis indicated that early motion after arthroscopic rotator cuff
      repair resulted in a significantly greater recovery of external rotation from pre
      operation to 3, 6, and 12 months post-operation (P < 0.05) and forward elevation
      ability from pre-operation to 6 months post-operation (P < 0.05), as compared to
      when motion was delayed. However, early motion resulted in non-significant excess
      (P > 0.05) in the rate of recurrence, compared to delayed motion. In addition,
      there were statistically higher rating scale of the American Shoulder and Elbow
      Surgeons (ASES) scores at 12 months post-operation (P < 0.05) and healing rates
      (P < 0.05) with delayed motion after arthroscopic rotator cuff repair, compared
      with early motion. CONCLUSION: Our meta-analysis included data from randomized
      controlled trials and demonstrated that delayed motion after arthroscopic rotator
      cuff repair resulted in higher healing rates and ASES scores than early motion.
      Alternatively, early motion increased range of motion (ROM) recovery, but also
      increased the rate of recurrence compared to delayed motion.

PMID- 26309486
TI  - The effect of green tea intake on risk of liver disease: a meta analysis.
AB  - AIM: There have been many reports on the reduction of liver disease with green
      tea consumption. This study aims to evaluate the body of evidence related to
      green tea consumption on the risk of liver disease and determine the
      effectiveness. METHODS: Electronic searches were conducted in PubMed, CNKI,
      Wanfang and Weipu databases. Statistical analysis was performed using the
      software Revman 5.2 and Stata 12.0. RESULTS: Meta-analysis revealed that among
      green tea drinkers, there was a significant reduction in the risk of liver
      disease (RR=0.68, 95% CI=0.56-0.82, P=0.000). This trend extends to a broad
      spectrum of liver conditions including hepatocellular carcinoma (RR=0.74, 95%
      CI=0.56-0.97, P=0.027), liver steatosis (RR=0.65, 95% CI=0.44-0.98, P=0.039),
      hepatitis (RR=0.57, 95% CI=0.45-0.73, P=0.000), liver cirrhosis (RR=0.56, 95%
      CI=0.31-1.01, P=0.053) and chronic liver disease (RR=0.49, 95% CI=0.29-0.82,
      P=0.007). This trend is also observed regardless of the race of the individual
      concerned where the Asian, American and European subgroups all demonstrated a
      reduced risk of liver disease. CONCLUSIONS: Green tea intake reduces the risk of
      liver disease. However, more long term randomized clinical trials are needed to
      comprehensively evaluate the health benefits of green tea.

PMID- 26309487
TI  - Does tea consumption correlate to risk of fracture? A meta-analysis.
AB  - Fractures are important causes of healthy damage and economic loss nowadays. The
      conclusions of observational studies on tea consumption and fracture risk are
      still inconsistent. The objective of this meta-analysis is to determine the
      effect of tea drinking on the risk of fractures. In this study, a comprehensive
      literature search was conducted in Pubmed, Embase and reference lists of the
      relevant articles. Observational studies that reported an estimate of the
      association between tea drinking and incidence of fractures were included. A meta
      analysis was conducted by the STATA software. The results indicated that a total
      of 9 studies involving 147,950 individuals that examined the association between
      tea consumption and risk of fractures were included in this meta-analysis. The
      odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using a random
      effects model. The pooled OR of 9 observational studies for the tea consumption
      on risk of fracture was 0.89 (95% CI, 0.78-1.04). In the subgroup analyses, no
      significant association was detected in neither cohort studies (n = 3; OR, 0.97;
      95% CI, 0.89-1.06) nor case-control studies (n = 6; OR, 0.91; 95% CI, 0.70-1.19),
      respectively. Because of the varied and limited data of the included studies, we
      are not able to conduct the dose-response meta-analysis. In conclusion, tea
      consumption might be not associated with the risk of fractures. The following
      large-sample and well-designed studies are required to confirm the existing
      conclusions. 

PMID- 26309488
TI  - Relationship between the concentration of formaldehyde in the air and asthma in
      children: a meta-analysis.
AB  - The aim of our study is to systematically assess the impact of formaldehyde in
      the air on asthma. Publications from year 1995 to 2014 on asthma were retrieved
      from PubMed, online Chinese periodical full-text databases of Chongqing VIP,
      China National Knowledge Index (CNKI) and Wan fang. Meta-Analyst was used to
      analyze the relationship between the concentration of formaldehyde and asthma in
      children. After evaluating the quality of the literature, 8 papers were finally
      included in our study, and the total sample sizes were 718, including the case
      group 362 and control group 356. The heterogeneous text display P=0.000,
      I(2)=0.876, Q=40.451, Meta-analyst finding showed that the pooled weighted mean
      difference (WMD) in concentration of formaldehyde is 0.021 (95% CI: 0.009-0.033).
      Children will have a larger probability to get asthma due to the higher level of
      formaldehyde. Therefore, we should reduce the level of formaldehyde in the air,
      which can protect our children. 

PMID- 26309489
TI  - The role of human cervical cancer oncogene in cancer progression.
AB  - Human cervical cancer oncogene (HCCR) was identified by differential display RT
      PCR by screened abnormally expressed genes in cervical human cancers. The
      overexpressed gene is not only identified in cervical tissues, but also in
      various human cancers as leukemia/lymphoma, breast, stomach, colon, liver, kidney
      and ovarian cancer. For its special sensitivities and specificities in human
      breast cancer and hepatocellular carcinoma, it is expected to be a new biomarker
      to replace or combine with the existing biomarkers in the diagnose. The HCCR
      manifests as a negative regulator of the p53 tumor suppressor gene, and its
      expression is regulated by the PI3K/Akt signaling pathway, modulated by TCF/beta
      catenin, it also participates in induction of the c-kit proto-oncogene, in
      activation of PKC and telomerase activities, but the accurate biochemical
      mechanisms of how HCCR contributes to the malignancies is still unknown. The aim
      of this review is to summarize the roles of HCCR in cancer progression and the
      molecular mechanisms involved. 

PMID- 26309490
TI  - Anti-angiogenesis or pro-angiogenesis for cancer treatment: focus on drug
      distribution.
AB  - Enhancing chemotherapy delivery to tumors, improving tumor growth control,
      reducing metastasis, and increasing survival are all critical objectives of
      improved cancer therapy. One of the obstacles to the success of anticancer
      therapies is related to the inefficient distribution of drugs to tumor cells. To
      be effective, chemotherapeutics must reach a concentration in cancer cells that
      is sufficient to inhibit its targets. In the past years, the vascular
      normalization theory has gained widespread acceptance for explaining additional
      antitumor effects of inhibitors of vascular endothelial growth factor (VEGF)
      signaling, when combined with chemotherapeutics. Vascular normalization is a
      strategy to enhance the antitumor effects of chemotherapeutics, but this is time
      and dose dependent and therefore difficult to implement clinically. Thus,
      alternative strategies that overcome these issues are needed. Accumulating
      scientific data demonstrate an alternative approach called "vascular promotion
      therapy" can increase chemotherapeutics delivery and intracellular uptake of the
      drug and reduces hypoxia by increasing tumor blood vessel density, blood flow,
      leakiness, and dilation, which leads to reduced cancer growth and metastasis. In
      this article, we first summarize the structural and functional abnormalities of
      the tumor microvasculature to highlight the importance of this phenomenon for
      chemotherapeutics distribution. Next, we summarize the limitations of anti
      angiogenic strategy in cancer treatment, discuss some key prototypical underlying
      mechanisms of vascular normalization and initial clinical evidence of vascular
      promotion therapy, and speculate on the clinical potential of anticoagulation as
      a novel paradigm to improve cancer treatment. 

PMID- 26309492
TI  - Effectiveness and safety of warfarin and anti-platelet drugs for the primary
      prevention of stroke in patients with non-valvular atrial fibrillation: a meta
      analysis.
AB  - OBJECTIVE: To evaluate the effectiveness and safety of warfarin and anti-platelet
      drugs as the primary approach to the prevention of stroke in patients with non
      valvular atrial fibrillation (NVAF). METHODS: Three English databases (the
      Cochrane library, Embase, and Medline), and three Chinese databases (the Chinese
      Biomedical Literature Database, Chinese National Knowledge Infrastructure, and
      Chinese Periodical Full-text Database of Science and Technology) were searched to
      select potentially eligible studies published before May, 2014. The studies were
      randomized controlled trials (RCTs) that investigated the effectiveness and
      safety of using warfarin and anti-platelet drugs in preventing stroke in NVAF
      patients; The statistical analysis was performed using the Review Manager 5.2
      software provided by the Cochrane Collaboration. RESULTS: nine articles were
      finally included. Compared with antiplatelet drugs, warfarin treatment
      significantly reduced the risk of stroke (OR = 0.62, 95% CI 0.50-05.77), systemic
      embolism events (OR = 0.49, 95% CI 0.31-0.77), ischemic stroke events (OR = 0.46,
      95% CI 0.36-0.59), stroke-related disability or death events (OR = 0.66, 95% CI
      0.52-0.84). Warfarin did not increase the incidence of All-cause death events (OR
      = 0.92, 95% CI 0.78-1.08), intracranial hemorrhage events (OR = 1.28, 95% CI 0.85
      1.93), major hemorrhage events (OR = 1.01, 95% CI 0.79-1.29). CONCLUSIONS: This
      meta-analysis found that compared with antiplatelet drugs, warfarin treatment
      significantly reduced the risk of stroke, systemic embolism events, ischemic
      stroke events, stroke-related disability or death events. And warfarin did not
      increase the incidence of All-cause death events, intracranial hemorrhage events,
      major hemorrhage events.

PMID- 26309493
TI  - The preparation of core/shell structured microsphere of multi first-line anti
      tuberculosis drugs and evaluation of biological safety.
AB  - To introduce a modified method, namely coaxial electrohydrodynamic atomization
      for the fabrication of distinct core/shell structured microspheres of four first
      line ant-tuberculosis drugs with different characteristics in hydrophilic
      properties in one single step. In group B, we prepared microspheres in which the
      core and the shell contain hydrophobic and hydrophilic drugs, respectively. In
      contrast, in group C, the opposite is prepared. The detection of encapsulation
      efficiency and in vitro release test were performed to confirm the feasibility of
      the drug-loaded core/shell structured microspheres. Moreover, cell culture
      experiments and animal experiments have been carried out to evaluate the
      biological safety of different microspheres in cell growth, cell viability,
      osteogenesis and migration of BMSCs in vitro and the bone fusion in a bone
      deficits model in SD rat. Meanwhile, the distribution of drugs and liver and
      kidney toxicity were monitored. The release patterns of the two groups are
      significantly different. The release of drugs from Group B microspheres is rather
      sequential, whereas group C microspheres release drugs in a parallel (co-release)
      manner. And various concentrations of carrier materials produces core/shell
      structured microspheres with different appearance. Moreover, the biological
      safety of core/shell structured microspheres was testified to be satisfactory.
      These findings present the advantages and possible application of this kind of
      multi-drug release system in treating skeletal tuberculosis. Moreover, the
      characteristic sequential release of multi-drugs can be controlled and adjusted
      based on treatment need and used in treating other disorders. 

PMID- 26309494
TI  - A meta-analysis of the effects of statin treatment on cardiovascular events and
      all-cause mortality in diabetic dialysis patients.
AB  - OBJECTIVES: Diabetic dialysis patients have higher risk of cardiovascular disease
      (CVD) than general population. While statin treatment is effective in prevention
      of CVD and all-cause mortality in general population, the use of statin in
      diabetic dialysis patients remains controversial. Thus, we aimed to assess the
      effects of statin treatment on prevention of CVD and all-cause mortality in
      diabetic dialysis patients by meta-analysis. MATERIALS AND METHODS: Pubmed,
      Embase and Cochrane Library were searched between each database's inception and
      July, 2014. Hazard ratio (HR) with 95% confidence interval (CI) for CVD and all
      cause mortality was extracted from each study. The pooled analysis was performed
      using random-effects models by Stata 12.0. RESULTS: Our search yielded five
      eligible articles including two RCTs and three observational studies. By pooled
      estimate, statin treatment was associated with a decreased risk of the cardiac
      endpoint which included cardiac death and nonfatal MI (HR=0.84, 95% CI: 0.78
      0.90) and all cardiac events combined (HR=0.89, 95% CI: 0.82-0.96). There was no
      difference in the overall incidence of fatal or nonfatal stroke (HR=1.24, 95% CI:
      0.99-1.53) and all cerebrovascular events combined (HR=1.14, 95% CI: 0.98-1.33)
      between statin treatment and control group. Finally, statin treatment was
      associated with a decreased risk of all-cause mortality (HR=0.81, 95% CI: 0.71
      0.92). CONCLUSIONS: Statin treatment may be beneficial for reducing the risk of
      cardiac events and all-cause mortality while have no effect on overall
      cerebrovascular events in diabetic dialysis patients. More RCTs were needed to
      validate the results.

PMID- 26309491
TI  - Genetics and gastric cancer susceptibility.
AB  - Gastric cancer has high morbidity and mortality in China. It is ranked first in
      malignant tumors of the digestive system. Its etiology and pathogenesis are still
      unclear, but they may be associated with a variety of factors. Genetic
      susceptibility genes have become a research hotspot in China. Elucidating the
      genetic mechanisms of gastric cancer can facilitate achieving individualized
      prevention and developing more effective methods to reduce clinical adverse
      consequences, which has important clinical significance. Genetic susceptibility
      results from the influence of genetic factors or specific genetic defects that
      endow an individual's offspring with certain physiological and metabolic features
      that are prone to certain diseases. Currently, studies on the genetic
      susceptibility genes of gastric cancer have become a hotspot. The purpose is to
      screen for the etiology of gastric cancer, search for gene therapy methods, and
      ultimately provide a scientific basis for the prevention and control of gastric
      cancer. This article reviews the current progress of studies on genetic
      susceptibility genes for gastric cancer. 

PMID- 26309495
TI  - Aldehyde dehydrogenase 1 expression correlates with clinicopathologic features of
      patients with breast cancer: a meta-analysis.
AB  - A number of studies have investigated the relationship between aldehyde
      dehydrogenase 1 (ALDH1) expression and the clinical pathological features of the
      patients with breast cancer. However, conclusions reported by different parties
      seem to be inconsistent. We have reviewed published studies and carried out this
      meta-analysis to provide credible results. We searched PubMed for articles
      published in English until September 12, 2014. Our main analyses were focused on
      the association between ALDH1 and the clinical pathological features, such as
      age, tumor size, nodal status, lymphovascular invasion, histological grade, and
      the expression of ER, PR, and HER2 by meta-analysis methods. If heterogeneity was
      observed, we used random effects model to calculate the overall odds ratios,
      otherwise fixed effects model was used. Twenty-one eligible studies were included
      in the present meta-analysis. From the pooled analyses, there was significant
      association between ALDH1 expression and histological grade (low vs.
      intermediate: pooled OR = 1.51, 95% CI: 1.09-2.10, P = 0.01; intermediate vs.
      high: pooled OR = 1.86, 95% CI: 1.12-3.07, P = 0.02), ER expression (pooled OR =
      0.41, 95% CI: 0.29-0.58, P < 0.00001), and PR expression (pooled OR = 0.56, 95%
      CI: 0.40-0.77, P = 0.0004). No clear correlation was found between ALDH1
      expression and age, tumor size, lymph node (LN) metastasis, lynphovascular
      invasion, and HER2 expression (P > 0.05). Despite the inconsistency in the
      published reports, this meta-analysis provides credible evidence to support the
      association between ALDH1 and breast cancer. However, it is necessary to conduct
      large sample studies using standardized and well-matched controls. 

PMID- 26309496
TI  - Biological effects of lentivirus-mediated silencing of minichromosome maintenance
      protein 7 with shRNA on the liver cancer MHCC-97H cells.
AB  - OBJECTIVE: This study was to specifically silence the minichromosome maintenance
      protein 7 (MCM7) expressions with lentivirus-mediated RNA interference technique
      in liver cancer MHCC-97H cells and its biological consequences were investigated.
      METHODS: Human MCM7 sequence was used for the design of shRNA targeting MCM7
      which was then introduced to lentivirus, followed by transfection into MHCC-97H
      cells. Real time quantitative PCR and Western blot assay were performed to detect
      the mRNA and protein expression of MCM7 in these cells. MTT assay was performed
      to detect cell proliferation, flow cytometry to detect cell cycle and apoptosis,
      scratch-wound assay to detect cell migration ability, and transwell invasion
      assay to evaluate the invasion of these cells. RESULTS: We successfully
      constructed LV-mcm7-RNAi expressing MCM7 shRNA. PCR and Western blot assay showed
      the mRNA and protein expression of MCM7 reduced significantly when compared with
      negative control group (LV-NC-RNAi) and blank control group (P<0.05). As compared
      to blank control group and negative control group, the cell proliferation reduced
      dramatically (P<0.01), cells were mainly arrested in G0/G1 phase and apoptotic
      cells increased markedly in LV-mcm7-RNAi group. Moreover, cells transfected with
      LV-mcm7-RNAi showed significant reductions in the invasion and migration as
      compared to other groups (P<0.05). CONCLUSION: Lentivirus mediated silencing of
      MCM7 with shRNA in MHCC-97H cells may inhibit the malignant behaviors of MHCC-97H
      cells (suppressed proliferation and compromised invasiveness), which is related
      to the cell cycle arrest and increase in apoptosis.

PMID- 26309497
TI  - Accuracy of different types of computer-aided design/computer-aided manufacturing
      surgical guides for dental implant placement.
AB  - PURPOSE: To evaluate the clinical outcomes of implants placed using different
      types of computer-aided design/computer-aided manufacturing (CAD/CAM) surgical
      guides, including partially guided and totally guided templates, and determine
      the accuracy of these guides Materials and methods: In total, 111 implants were
      placed in 24 patients using CAD/CAM surgical guides. After implant insertion, the
      positions and angulations of the placed implants relative to those of the planned
      ones were determined using special software that matched pre- and postoperative
      computed tomography (CT) images, and deviations were calculated and compared
      between the different guides and templates. RESULTS: The mean angular deviations
      were 1.72 +/- 1.67 and 2.71 +/- 2.58, the mean deviations in position at the neck
      were 0.27 +/- 0.24 and 0.69 +/- 0.66 mm, the mean deviations in position at the
      apex were 0.37 +/- 0.35 and 0.94 +/- 0.75 mm, and the mean depth deviations were
      0.32 +/- 0.32 and 0.51 +/- 0.48 mm with tooth- and mucosa-supported
      stereolithographic guides, respectively (P < .05 for all). The mean distance
      deviations when partially guided (29 implants) and totally guided templates (30
      implants) were used were 0.54 +/- 0.50 mm and 0.89 +/- 0.78 mm, respectively, at
      the neck and 1.10 +/- 0.85 mm and 0.81 +/- 0.64 mm, respectively, at the apex,
      with corresponding mean angular deviations of 2.56 +/- 2.23 degrees  and 2.90 +/-
      3.0 degrees  (P > .05 for all). CONCLUSIONS: Tooth-supported surgical guides may
      be more accurate than mucosa-supported guides, while both partially and totally
      guided templates can simplify surgery and aid in optimal implant placement.

PMID- 26309499
TI  - Inhibition of MiR-155 suppresses cell migration in nasopharyngeal carcinoma
      through targeting ZDHHC2.
AB  - Overexpression of miR-155 in nasopharygeal carcinoma (NPC) is partly driven by
      Epstein-Bar virus infection. However the role of miR-155 in NPC oncogenesis is
      unclear. This study showed that miR-155 inhibitor could inhibit the cell
      migration in NPC cell lines. ZDHHC2 was identified as a direct target of miR-155
      and downregulation of ZDHHC2 prompted cell migration in NPC. Furthermore, reduced
      ZDHHC2 expression was associated significantly with metastasis and poor survival
      of NPC patients. Collectively, inhibition of miR-155 suppresses cell migration in
      NPC through targeting ZDHHC2. The potential of miR-155 and ZDHHC2 as therapeutic
      targets in NPC should be further investigated. 

PMID- 26309500
TI  - Meridian-sinew release therapy for the treatment of refractory rheumatoid
      arthritis.
AB  - OBJECTIVE: To evaluate the efficacy and safety of Meridian-sinew Release therapy
      in Chinese patients with refractory active Rheumatoid Arthritis (RA). SUMMARY OF
      BACKGROUND DATA: Few studies focused on the effect of combination of Meridian
      sinew Release therapy and Methotrexate (MTX) on refractory active RA of Chinese
      patients. METHODS: Eighty refractory active rheumatoid arthritis patients were
      randomized to receive Meridian-sinew Release+MTX 10 mg (n=40), MTX 10 mg (n=40)
      every week for 12 weeks. The primary end point was the proportion of patients
      achieving >=20% improvement in the American College of Rheumatology criteria
      (ACR20) at week 12. Secondary efficacy endpoints included 28-joint disease
      activity score with ESR (DAS28-ESR), simplified disease activity index (SDAI),
      clinical disease activity index (CDAI) and Health Assessment Questionnaire
      Disability Index (HAQ-DI). RESULTS: Week 12 ACR20 response rates were
      significantly greater in Meridian-sinew Release+MTX group (30/38 (78.9%)) than in
      MTX group (19/37 (51.3%)), (P<0.001), as were ACR50 and ACR70 response rates.
      Patients treated with Meridian-sinew Release+MTX were significantly more likely
      to achieve clinical remission, using various definitions, at 12 weeks versus MTX
      alone. A larger percentage of Meridian-sinew+MTX patients than MTX alone patients
      were in states of low disease activity or remission for DAS28-ESR, SDAI and CDAI
      after 12 weeks of treatment. CONCLUSION: Our study suggests that Meridian-sinew
      Release therapy was well tolerated and efficacious in improving clinical outcomes
      in Chinese patients with refractory active RA.

PMID- 26309501
TI  - Ikaros6 is associated with BCR-ABL1 and myeloid-associated antigens but indicates
      poor prognosis independently in Chinese adult B-cell acute lymphoblastic
      leukemia.
AB  - Ikaros6 was specifically associated with clinical and genetic features of acute
      lymphoblastic leukemia (ALL) and could be used for prediction of inferior
      survival. The present study aimed to further investigate the correlation between
      Ikaros6 and other prognostic factors, and to explore the novel prognosis
      prediction function by combining Ikaros6 and other factors in Chinese adult B
      ALL. We examined the expression of Ikaros6 in 108 patients by reverse
      transcription polymerase chain reaction and confirmed the results by sequencing,
      gene scanning and real-time PCR. Ikaros6 was associated with BCR-ABL1 (P=0.010)
      and myeloid-associated antigens (P=0.009), but had an independent negative impact
      on survival. In multivariable Cox analysis, Ikaros6 was an independent prognostic
      marker for overall survival (P=0.013, HR=2.140), event-free survival (P=0.016,
      HR=1.972) and relapse-free survival (P=0.002, HR=3.636). This study indicated
      closed relation between BCR-ABL1, myeloid-associated antigens and Ikaros6.These
      three risk factors played an important role in evaluation of prognosis in Chinese
      adult B-ALL. Furthermore, Ikaros6 is more beneficial for the disease recurrence
      prediction. 

PMID- 26309498
TI  - Efficacy of dexmedetomidine on postoperative nausea and vomiting: a meta-analysis
      of randomized controlled trials.
AB  - PURPOSE: Postoperative nausea and vomiting (PONV) is a frequent complication in
      postoperative period. The aim of the current meta-analysis was to assess the
      efficacy of dexmedetomidine on PONV. METHODS: Two researchers independently
      searched PubMed, Embase and Cochrane Central Register of Controlled Trials for
      randomized controlled trials (RCTs). The meta-analysis was performed with Review
      Manager. RESULTS: Eighty-two trials with 6,480 patients were included in this
      meta-analysis. Dexmedetomidine reduced postoperative nausea (Risk Ratio (RR) =
      0.61, 95% confidence interval (CI): 0.50 to 0.73) and vomiting (RR = 0.48, 95%
      CI: 0.36 to 0.64) compared with placebo, with an effective dose of 0.5 MUg/kg (RR
      = 0.46, 95% CI: 0.34 to 0.62) and 1.0 MUg/kg (RR = 0.29, 95% CI: 0.12 to 0.75),
      respectively. The antiemetic effect can only be achieved intravenously, not
      epidurally or intrathecally. The efficacy of dexmedetomidine was similar to that
      of widely used agents, such as propofol, midazolam etc., but better than opioid
      analgesics. Moreover, application of dexmedetomidine reduced intraoperative
      requirement of fentanyl (Standard Mean Difference = -1.91, 95% CI: -3.20 to 
      0.62). CONCLUSIONS: The present meta-analysis indicates that dexmedetomidine
      shows superiority to placebo, but not to all other anesthetic agents on PONV. And
      this efficacy may be related to a reduced consumption of intraoperative opioids.

PMID- 26309502
TI  - Ultrasound elastography and magnetic resonance examinations are effective for the
      accurate diagnosis of mammary duct ectasia.
AB  - OBJECTIVES: This study is to investigate the values of multiple quantitative
      evaluation parameters in the diagnosis of mammary duct ectasia (MDE), using real
      time ultrasound elastography (UE) and magnetic resonance imaging (MRI). METHODS:
      This retrospective study was performed on 15 patients (16 lesions) with MDE.
      Ultrasound examination was performed with the LOGIQ E9 ultrasound instrument,
      with all lesions being examined by routine ultrasound and UE. MRI examination was
      performed with a Signa HD * 3.0T TWINSP MR System, including of plain-scan,
      diffusion-weighted imaging, dynamic contrast-enhanced MRI, and proton magnetic
      resonance spectroscopy. Imaging features, as well as semi-quantitative and
      quantitative parameters, were analyzed to determine their diagnostic value for
      MDE. RESULTS: According to the five-point scale in UE, twelve lesions belonged to
      1-3 point scale, and four lesions were in 4-5 point scale, with an average of
      2.93 +/- 0.77. In dynamic contrast-enhanced MRI, the lesions appeared as
      obviously enhanced signals. The MRI early-enhancement rate ranged from 0.35 to
      1.07 (0.67 +/- 0.30 on average); the time peak ranged between 192 and 330 s (248
      +/- 37 s on average); the peak-enhancement ratio ranged from 2.26 to 3.06, with
      an average of 2.59 +/- 0.33. According to MRI time-signal intensity curves
      classified into persistently enhancing (type I), plateau (type II) and washout
      (type III), 12 lesions (75%) belonged to type I, three (18.75%) belonged to type
      II, and one (6.25%) belonged to type III. Magnetic resonance spectroscopy showed
      that a total choline peak occurred only in one lesion. The diagnosis accuracy
      rates for ultrasound alone, MRI alone and the combination of ultrasound and MRI
      were 75% (12/16), 87.5% (14/16) and 93.75% (15/16), respectively. CONCLUSIONS:
      Both ultrasound and MRI show clinical importance in MDE diagnosis. However, UE,
      dynamic contrast-enhanced MRI, and magnetic resonance spectroscopy demonstrate
      significantly better diagnosis and differential diagnosis of MDE.

PMID- 26309503
TI  - Diagnostic accuracy of exhaled nitric oxide in asthma: a meta-analysis of 4,691
      participants.
AB  - Asthma is a common airway inflammation, but current methods for diagnosing it are
      poor. Here we meta-analyze the available evidence on the ability of exhaled
      nitric oxide (eNO) in asthma to serve as a diagnostic marker of asthma. We
      systematically searched the PubMed and EMBASE databases, published data on
      sensitivity, specificity and other measures of diagnostic accuracy of eNO in the
      diagnosis of asthma were meta-analyzed. The methodological quality of each study
      was assessed by QUADAS-2 (quality assessment for studies of diagnostic accuracy).
      Statistical analysis was performed by employing Meta-Disc 1.4 software and STATA.
      And the measures of accuracy of eNO in the diagnosis of asthma were pooled using
      random-effects models. A total of nineteen publications reporting twenty-one case
      control studies were identified. Pooled results indicated that eNO showed a
      diagnostic sensitivity of 0.78 (95% CI 0.76 to 0.80), specificity was 0.74 (95%
      CI 0.72 to 0.76). PLR was 3.70 (95% CI 2.84 to 4.81) and NLR was 0.35 (95% CI
      0.26 to 0.47). DOR was 11.37 (95% CI 7.54 to 17.13). Exhaled nitric oxide show
      insufficient sensitivity and specificity for diagnosing asthma, eNO measurements
      may be useful in combination with clinical manifestations and conventional tests
      such as pulmonary function tests, assessment of bronchodilator response and
      bronchial challenge tests. 

PMID- 26309504
TI  - Prognostic significance of STAT3/phosphorylated-STAT3 in tumor: a meta-analysis
      of literatures.
AB  - PURPOSE: The prognostic value of the expression of STAT3/phosphorylated-STAT3 on
      survival for cancer patients remains controversial. We performed a meta-analysis
      of the published literature in this field to identify its impact. METHODS: We
      conducted a meta-analysis of 26 studies (n=3877 patients) that evaluated the
      relationship between the prognostic value and the expression of
      STAT3/phosphorylated-STAT3 in 15 different kinds of carcinomas. Studies evaluated
      the correlation between STAT3/phosphorylated-STAT3, which detected mostly by
      immunohistochemistry and western blot, and clinical staging, overall survival
      (OS) and disease free survival (DFS) were included. The impact of STAT3 and
      phosphorylated-STAT3 was analyzed separately. RESULTS: A total of 26 studies (14
      for STAT3 and 16 for phosphorylated-STAT3), comprising 3877 patients, were
      included for meta-analysis. The expression of STAT3 was strongly associated with
      a poor impact on overall survival (OS) in all eligible studies [hazard ratio
      (HR)=2.91, (95% confidence interval (CI), 1.91-4.42)], while a significant
      association was shown between the expression of phosphorylated-STAT3 and
      patients' outcome [HR=1.53, (95% CI, 0.86-2.70)]. No significant effect was shown
      between the expression of STAT3/phosphorylated-STAT3 and clinical staging,
      neither with DFS. CONCLUSION: High expression of STAT3 seems to be associated
      with poor OS in patients with carcinomas, while phosphorylated-STAT3 does not.

PMID- 26309505
TI  - The dynamic impact of hydrodynamic gene transfer on the immune system.
AB  - Hydrodynamic gene transfer (HGT) has been used as an effective and convenient way
      to achieve gene expressions in vivo. However, its time-dependent impact on the
      immune system is unknown. The aim of the current study is to investigate the
      dynamic changes of the immune parameters after HGT. Plasmids were delivered to
      BALB/c mice by HGT. Each group of mice was sacrificed on day 1, 2, 3, 4 and 5
      after HGT. The immune cell subsets from spleens and livers were analyzed by flow
      cytometry. IFN-gamma, IL-6 and TNF-alpha in the serum were quantitated by
      cytometric bead array. The mice without HGT injection were used as control group
      on day 0. Compared to the normal mice (day 0), the T lymphocyte infiltrations in
      the spleen and liver were increased starting from day 1 after HGT. T cells. NK
      cells and myeloid cells such as dendritic cells, neutrophils and macrophages were
      also significantly expanded and peaked around day 2-3. Both T cells and NK cells
      were greatly activated. Serum levels of IFN-gamma and IL-6 increased and peaked
      on day 1 after HGT. Most of the increased immune parameters returned to normal
      levels after day 4. However, the activated T cells remained at a high level,
      especially in the liver. In conclusion, HGT significantly increased the immune
      cell infiltration in the spleen and liver and activated T cells and NK cells. The
      immune response induced by HGT should be taken into consideration when evaluating
      the functions of the over-expressed genes using this strategy. 

PMID- 26309506
TI  - Uighur medicine abnormal savda munzip (ASMq) suppresses expression of collagen
      and TGF-beta1 with concomitant induce Smad7 in human hypertrophic scar
      fibroblasts.
AB  - BACKGROUND: Hypertrophic scar (HS) is a common dermal disease, for which numerous
      treatments are currently available but they do not always yield excellent
      therapeutic results. Hence, alternative strategy are needed. Recent basic and
      clinic research has shown that Uighur medicine abnormal savda munzip (ASMq) has
      anti-hypertrophic scar properties but its molecular mechanism is unknown. The aim
      of this study was to explore the effect of ASMq on TGF-beta/Smads signaling in
      fibroblasts derived from hypertrophic scar. PURPOSE: To investigate the effect of
      ASMq on the TGF-beta/Smads signaling pathway in hypertrophic scar fibroblasts
      (HSFs). METHODS: Hypertrophic scar fibroblasts (HSFs) were isolated from human of
      hypertrophic scar and passaged to the 3~4 generation, which were treated with the
      different concentrations of ASMq. Cells treated with 5-Fu served as the positive
      control group. After treatment for 48 hours, expressions of Smad7, TGF-beta1,
      type I and III collagen, were examined by immunocytochemistry, reverse
      transcription PCR and Western blotting, respectively. RESULTS: ASMq markedly
      enhanced the expression of inhibitory Smad7, with suppression of type I and III
      collagen and TGF-beta1. We observed that treatment of ASMq induced Smad7 to enter
      the cytoplasm from the nucleus of hypertrophic fibroblasts. CONCLUSIONS: ASMq
      inhibits scarring probably by enhancing the expression of inhibitory Smad7, and
      inhibiting TGF-beta1, collagen expression, and is a potential treatment for
      scarring.

PMID- 26309507
TI  - Variants on 8q24 and prostate cancer risk in Chinese population: a meta-analysis.
AB  - Previous studies have identified 8q24 as an important region to prostate cancer
      (PCa) susceptibility. The aim of this study was to investigate the role of six
      genetic variants on 8q24 (rs1447295, A; rs6983267, G; rs6983561, C; rs7837688, T;
      rs10090154, T and rs16901979, A) on PCa risk in Chinese population. Online
      electronic databases were searched to retrieve related articles concerning the
      association between 8q24 variants and PCa risk in men of Chinese population
      published between 2000 and 2014. Odds ratio (ORs) with its 95% correspondence
      interval (CI) were employed to assess the strength of association. Total eleven
      case-control studies were screened out, including 2624 PCa patients and 2438
      healthy controls. Our results showed that three risk alleles of rs1447295 A
      (OR=1.35, 95% CI=1.19-1.53, P<0.00001), rs6983561 C (C vs. A: OR=1.41, 95%
      CI=1.21-1.63, P<0.00001) and rs10090154 T (T vs. C: OR=1.48, 95% CI=1.22-1.80,
      P<0.00001) on8q24 were significantly associated with PCa risk in Chinese
      population. Furthermore, genotypes of rs1447295, AA+AC; rs6983561, CC+AC and CC;
      rs10090154, TT+TC; and rs16901979, AA were associated with PCa as well (P<0.01).
      No association was found between rs6983267, rs7837688 and PCa risk. In
      conclusions, variants including rs1447295, rs6983561, rs10090154 and rs16901979
      on 8q24 might be associated with PCa risk in Chinese population, indicating these
      four variations may contribute risk to this disease. This meta-analysis was the
      first study to assess the role of 8q24 variants on PCa risk in Chinese
      population. 

PMID- 26309508
TI  - Biomechanical evaluation of four different posterior screw and rod fixation
      techniques for the treatment of the odontoid fractures.
AB  - Problems that screw cannot be inserted may occur in screw-rod fixation techniques
      such as Harms technique. We compared the biomechanical stability imparted to the
      C-2 vertebrae by four designed posterior screw and rod fixation techniques for
      the management of odontoid fractures. A three-dimensional finite element model of
      the odontoid fracture was established by subtracting several unit structures from
      the normal model from a healthy male volunteer. 4 different fixation techniques,
      shown as follows: 1 C-1 lateral mass and C-2 pedicle screw fixation (Harms
      technique); 2 C-1 lateral mass and unilateral C-2 pedicle screw fixation combined
      with ipsilateral laminar screw fixation; 3 Unilateral C-1lateral mass combined
      with ipsilateral C-1 posterior arch, and C-2 pedicle screw fixation; and 4
      Unilateral C1 lateral mass screw connected with bilateral C2 pedicle screw
      fixation was performed on the odontoid fracture model. The model was validated
      for axial rotation, flexion, extension, lateral bending, and tension for 1.5 Nm.
      Changes in motion in flexion-extension, lateral bending, and axial rotation were
      calculated. The finite element model of the odontoid fracture was established in
      this paper. All of the four screw-rod techniques significantly decreased motion
      in flexion-extension, lateral bending, and axial rotation, as compared with the
      destabilized odontoid fracture complex (P<0.05). There was no statistically
      significant difference in stability among the four screw techniques. We concluded
      that the first three fixation techniques are recommended to be used as surgical
      intervention for odontoid fracture, while the last can be used as supplementary
      for the former three methods. 

PMID- 26309509
TI  - Protective immunity of rAd5/NR2B vaccine against concomitant aversiveness of
      spontaneous neuropathic pain following spinal nerve ligation injury.
AB  - OBJECTIVE: Peripheral nerve injury elicits an aversive state of spontaneous
      neuropathic pain, and up to now, the modulation of this concomitant aversive
      state remains a major therapeutic challenge. NMDA receptor subunits NR2B in the
      rACC are critically involved in the processing of this aversive state and then a
      strategy targeted at the NR2B subunit might be promising for modulation of the
      aversive state. Thus, in the present study, using negative reinforcement animal
      model to reveal spontaneous pain, we investigated the effect of oral immunization
      with recombinant adenovirus serotype 5-mediated NR2B gene transfer (rAd5/NR2B) on
      the modulation of the tonic pain. MATERIAL AND METHODS: Following oral
      administration of the rAd5/NR2B vaccine, NR2B-specific antibodies were induced in
      serum. And the humoral response was involved in the decreased expression of NR2B
      protein in the rACC. RESULTS: The present study demonstrated that CPP achieved by
      spinal administration of clonidine in spinal nerve ligation (SNL) rats revealed
      the presence of aversive state of spontaneous neuropathic pain. Notably, the
      humoral autoimmune response blocked the CPP by spinal clonidine, suggesting the
      relief of the concomitant aversive of spontaneous neuropathic pain in the SNL
      rats. CONCLUSION: These data proved the feasibility of oral immunization with
      rAd5/NR2B for modulation of concomitant aversive of spontaneous neuropathic pain
      due to peripheral nerve injury.

PMID- 26309510
TI  - MicroRNA-145 inhibits human papillary cancer TPC1 cell proliferation by targeting
      DUSP6.
AB  - MicroRNAs (miRNAs) are small, non-coding RNAs that modulate gene expression by
      negatively regulating the stability or translational efficiency of their target
      mRNAs. The aim of this study was to investigate the expression of microRNA-145
      (miR-145) in human papillary thyroid cancer and its potential function.
      Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was
      performed to determine the expression level of miR-145 in ten papillary thyroid
      cancer and adjacent normal specimens. The function of miR-145 overexpression on
      the proliferation of human TPC1 thyroid cancer cells was conducted by MTT assays
      and by colony-formation assays. Western blot was used to validate the impact of
      miR-145 on the protein expression of the target gene. Luciferase reporter assays
      were employed to validate a putative target of miR-145. MiR-145 expression was
      relatively decreased in papillary thyroid cancer specimens compared with adjacent
      normal tissues (P<0.05). MTT assays and colony-formation assays showed that
      overexpression of miR-145 suppressed TPC1 cell growth. Luciferase assays using a
      reporter carrying a putative miR-145 target site in the 3' untranslated region of
      DUSP6 revealed that miR-145 directly targets DUSP6. Overexpression of miR-145 led
      to downregulation of DUSP6 at protein level as assessed by Western blot. Targeted
      knockdown of DUSP6 by siRNA significantly inhibited the proliferation of TPC1
      cells. The overexpression of miR-145 inhibited TPC1 cellular growth by targeting
      DUSP6; this finding implies a better understanding of initiation and progression
      of papillary thyroid cancer. 

PMID- 26309511
TI  - TSPAN8 promotes gastric cancer growth and metastasis via ERK MAPK pathway.
AB  - AIMS: This study was designed to investigate the effects of Tetraspanin 8
      (TSPAN8) overexpression and TSPAN8 suppression on gastric cancer cell
      proliferation and invasion. Furthermore, whether extracellular-signal regulated
      kinase (ERK) mitogen-activated protein kinase (MAPK) pathway was involved in
      TSPAN8's function on gastric cancer cells was examined. METHODS: The expression
      of TSPAN8 in human gastric cancer tissues and gastric cancer cell lines was
      detected using real-time PCR and western blot analysis. TSPAN8-pcDNA3.1 plasmid
      or TSPAN8 siRNA was transfected into the gastric cancer cell lines to overexpress
      or suppress TSPAN8. Cells were treated with U0126 to inhibit ERK MAPK pathway.
      Cell proliferation and invasion were assessed by MTT and transwell-matrigel
      assay. RESULTS: TSPAN8 was overexpressed in human gastric cancer tissues and
      gastric cancer cell lines compared with the normal. TSPAN8 overexpression
      promoted cell proliferation and invasion, while TSPAN8 suppression inhibited cell
      proliferation and invasion. TSPAN8 could activate the ERK MAPK pathway in gastric
      cancer cells, and MEK-ERK inhibition reversed the effects of TSPAN8
      overexpression on cell proliferation and invasion. CONCLUSION: This study firstly
      demonstrated that TSPAN8 promotes gastric cancer cell growth and metastasis at
      least partially through the activation of ERK MAPK pathway. These findings
      provided a novel molecular basis for the understanding and treatment of gastric
      cancer.

PMID- 26309512
TI  - Effects of icariin on orthodontic tooth movement in rats.
AB  - PURPOSE: Orthodontic tooth movement (OTM) is achieved through bone remodeling of
      the alveolar bone. Icariin, the active ingredient isolated from Herba Epimedii
      which is a traditional Chinese medicine (TCM) commonly used for osteoporosis
      treatment in China. The purpose of the study is to explore the effect of icariin
      on OTM in rats, and analyze the possible mechanism involved. METHODS: 48 rats
      were selected and divided into 2 groups: the control group and the experimental
      group. Rats in the experimental group were given 20 mg/kg/day icariin by
      intragastric administration, while the control group received the same volume
      solvent. All rats were placed a closed coil spring between their upper first
      molar and incisor, exerting a force of about 40 g to establish animal models of
      OTM. As the first molar moved mesially, a space between the first and second
      molar was created. The rats were sacrificed in batch on the 7th, 14th, 21st and
      28th days after orthodontic treatment. The amount of tooth movement was measured,
      and histomorphometric analysis based on slices from periodontium adjacent to the
      maxillary first molars were used to observe new bone formation, bone resorption
      and quantify osteoclasts. KEY RESULTS: Icariin increased OTM (P<0.05) by 65.2%,
      35.3%, 11.7% and 16.7% on day 7, 14, 21, 28 respectively compared with the
      control group. The number of osteoclasts in the icariin group showed a transient
      but sudden increase and then a persistent decrease. CONCLUSIONS: Icariin could
      accelerate OTM in rats through promoting bone remodeling of alveolar bone.

PMID- 26309513
TI  - Clinical efficacy and safety of ICS/LABA in patients with combined idiopathic
      pulmonary fibrosis and emphysema.
AB  - The study aim was to explore the clinical efficacy and safety of inhaled
      corticosteroids (ICS)/long-acting beta2-agonists (LABA) in combined with
      idiopathic pulmonary fibrosis and emphysema. 45 patients with combined idiopathic
      pulmonary fibrosis and emphysema (CPFE) who were treated with ICS/LABA (Group A),
      24 patients with CPFE who were treated without ICS/LABA (Group B) and 35 patients
      with idiopathic pulmonary fibrosis (IPF) (Group C) were enrolled into this study.
      Then, clinical efficacy and safety of ICS/LABA was analyzed through lung function
      scores and lung high-resolution computed tomography (HRCT) scans. Compared with
      baseline levels, the FEV1%, FVC% and DLCO% levels were increased 11.2%, 13.53%
      and 12.8% respectively in group A, but declined 14.21%, 16.8% and 21.25%
      respectively in group B, meanwhile, lung HRCT score was declined 9.31 in group A
      but increased 14.87 in group B, and there was significant difference between
      group A and group B (P<0.01). Furthermore, the acute outbreak frequency was 44.4%
      and 75% in group A and B respectively within 12 months (P<0.05); moreover, CPI
      index and HRCT score were both lower in group A than those in group B in acute
      episode period (P<0.05), but there was no significant difference of PO2 value
      between group A and B (P>0.05). The incidence of adverse reaction was higher in
      group A than that in group B during this study, but there was no significant
      difference (P>0.05). ICS/LABA therapy could improve lung function condition in
      patients with CPFE and declined acute out-break frequency and severity of
      diseases during acute episode period. 

PMID- 26309514
TI  - 4-Hydroxyisoleucine improves hepatic insulin resistance by restoring glycogen
      synthesis in vitro.
AB  - INTRODUCTION/AIMS: Hydroxyisoleucine (4-HIL), derived from fenugreek seeds,
      improves insulin resistance in 3T3-L1 adipocytes and L6 myotubes. However, the
      effects of 4-HIL on liver glycogen synthesis and hepatic insulin resistance have
      not been described. The aim of this study was to investigate the effects of 4-HIL
      on glycogen synthesis in a tumor necrosis factor-alpha (TNF-alpha)-induced
      insulin resistance model using HepG2 cells. MATERIALS AND METHODS: HepG2 cells
      were divided into eight groups: control; TNF-alpha; and 5, 10, or 20 MUM 4-HIL
      without or with TNF-alpha. Glycogen and protein expression were evaluated using a
      glycogen assay kit and western blotting, respectively. RESULTS: Glycogen levels
      did not differ between the 4-HIL groups and control (P>0.05), but were decreased
      significantly in the TNF-alpha group (P<0.05), indicating the establishment of
      insulin-resistant HepG2 cells. Adding 20 MUM 4-HIL to TNF-alpha-treated cells
      increased glycogen levels (P<0.05). Relative to the control group, the P-IRS
      1/IRS-1 and P-JNK/JNK ratios were increased (P<0.001) in the TNF-alpha group,
      whereas the P-AKT/AKT and P-GSK/GSK ratios were decreased (P<0.001). When 20 MUM
      4-HIL was added to TNF-alpha-treated cells, the P-IRS-1/IRS-1 and P-JNK/JNK
      ratios decreased (P<0.001 and P<0.05, respectively), whereas the P-AKT/AKT and P
      GSK/GSK ratios increased (P<0.05 and P<0.001). CONCLUSIONS: 4-HIL directly or
      indirectly reversed TNF-alpha reduced glycogen levels by inhibiting JNK and IRS-1
      (Ser(307)) phosphorylation and increasing AKT (Ser(473)) and GSK-3
      phosphorylation. These findings demonstrate that 4-HIL modulates hepatic insulin
      resistance at the molecular level, and suggest that it is a novel potential
      therapeutic agent for the treatment of insulin resistance in patients with
      diabetes.

PMID- 26309515
TI  - A novel guide device improves the accuracy of pedicle screw placement.
AB  - Pedicle screw placement in thoracic and lumbar spine is technically demanding and
      involves radiation exposure. Commercially available systems for pedicle screw
      insertion are expensive and cannot be widely used for those less-developed areas.
      The purpose of our study was to develop a simple guide device assisting pedicle
      screw placement and improving the accuracy in the operation. A simple guide
      device was developed with the aim of improving accuracy of pedicle screw
      technique based on anatomical structures of the spine. We retrospectively
      collected clinical data of 111 consecutive patients who received treatment of
      pedicle screw internal fixation between January 2013 and September 2014. In
      total, 518 screws were inserted by the same surgeon, among which 280 screws were
      implanted in 60 patients (33 males and 27 females) with conventional freehand
      technique and 238 screws were implanted in 51 patients (27 males and 24 females)
      using the guide device. According to postoperative CT evaluation, screws were
      classified into different grades and accuracy rates were compared between the two
      groups. A total of 518 screws were placed (238 in the guide group, 280 in the
      conventional group). No intra-operative or postoperative complications such as
      infection, vessel and nerve injuries occurred. After postoperative CT evaluation,
      215 from guide group and 236 from the conventional group were classified in Grade
      1. Only screws in Grade 1 were considered as accurate insertion. Thus, the
      accuracy rates were 84.3% for the conventional group and 90.3% for the guide
      group respectively. Through statistical test, there was significant difference in
      the accuracy rate between two groups. The simple guide device significantly
      improves the accuracy of pedicle screw placement. Combined with the advantage of
      cheapness, it can be widely used in spinal internal fixations, especially
      suitable for those inexperienced spine surgeons in less-developed areas. 

PMID- 26309516
TI  - Berberine attenuates cigarette smoke-induced airway inflammation and mucus
      hypersecretion in mice.
AB  - Cigarette smoke-induced airway inflammationmucus over-production is one of the
      most important pathogenic features of chronic airway diseases. This study aimed
      to investigate the effect of berberine, a plant alkaloid with strong anti
      inflammatory property, on cigarette smoke-induced airway inflammation and
      mucushypersecretion in mice. Mice with exposure to cigarette smoke
      wereintraperitonealy injected with berberin (5, 10 mg/kg.d). Inflammatory
      cytokines TNF-alpha, IL-1beta and MCP-1 levels in bronchoalveolar lavage fluid
      were determined by ELISA.Lung tissue was examined for histopathological lesions
      and goblet cell hyperplasia. The expression of signaling proteins in lung tissue,
      ERK and P38 were detected using Western Blot. Cigarette smoke exposure
      significantly increased the release of inflammatory cytokines TNF-alpha, IL
      1beta, MCP-1 and inflammatory cells in bronchoalveolar lavage fluid, and it also
      induced goblet cell hyperplasiaand the expression of mucin-5ac in the airway of
      mice. Pretreatment of berberineinhibited cigarette smoke-induced airway
      inflammation and mucus production. Cigarette smoke exposure also increased the
      expression of ERK and P38, meanwhile, berberineintervention can inhibit such
      changes. In summary, berberine inhibits cigarette smoke exposure-induced airway
      inflammation and mucus hypersecretion in mice, which may partly act through
      inhibition of ERK and P38. 

PMID- 26309517
TI  - Effects of Gengnianchun on learning and memory ability, neurotransmitter,
      cytokines, and leptin in ovariectomized rats.
AB  - This study aimed to evaluate the beneficial effects of a traditional Chinese
      medicine named Gengnianchun (GNC) in ovariectomized Sprague-Dawley rats. The rats
      were randomly categorized into sham-operated group (Sham), saline-treated
      ovariectomized group (OVX), GNC-treated ovariectomized group (OVX+GNC), estradiol
      valerate-treated ovariectomized group (OVX+E). GNC and estradiol was administered
      for 1 month at dosages of 125 and 0.1 mg/day, respectively. Ovariectomy caused
      deterioration of learning and memory ability (P < 0.05), which was restored by
      treatment with GNC and estradiol (P < 0.05). Estrogen level and endometrial
      thickness significantly decreased in the OVX group (P < 0.05). These parameters
      significantly increased in the OVX+E group (P < 0.05) but did not change in the
      OVX+GNC group (P > 0.05). GNC and estradiol significantly increased the levels of
      norepinephrine (NE) and dopamine (DA) and decreased the levels of 5
      hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the
      hypothalamus (P < 0.05). The levels of interleukin-1 beta (IL-1beta), interleukin
      6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) significantly decreased and
      the levels of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) increased in
      the OVX+GNC and OVX+E groups compared with those in the OVX group (P < 0.05). OVX
      rats treated with GNC and estradiol further exhibited reversed ovariectomy
      induced weight gain and leptin resistance (P < 0.05). These results indicated
      that GNC demonstrated phytoestrogen-like properties without the side effects of
      estradiol valerate. Thus, GNC may confer protective and beneficial effects for
      management of menopausal syndrome. 

PMID- 26309518
TI  - Efficacy of concurrent single-agent chemotherapy using radiotherapy in patients
      with cervical cancer: a meta-analysis.
AB  - Concurrent chemoradiotherapy has proven to be more effective on patients with
      advanced cervical cancer than radiotherapy alone. Although cisplatin has been
      recommended to be the standard agent in chemotherapy, it has some limitations in
      clinical use because of its strong side effects. Moreover, the optimal
      chemotherapy regimen remains unclear. A comprehensive electronic search was
      conducted via the Internet retrieval system to identify eligible trials. The
      ending points included response, overall survival (OS), local recurrent, and
      distant metastasis rates. Odds ratios and 95% confidence interval were calculated
      to compare the effects. Fifteen trials with 1142 patients were eligible. With
      regard to the response rate, only nedaplatin showed a significant improvement
      compared with cisplatin. Docetaxel, pacitaxel, fluoropyrimidine, paclitaxel
      liposome, and irinotecan did not show any advantages. When targeted on OS or
      local recurrent rate, no significant advantage was found when these single-drug
      regimens were compared with cisplatin. However, when aimed at distant metastasis
      rate, fluoropyrimidine showed a disadvantage to cisplatin, whereas others showed
      equal efficacy. Nedaplatin, docetaxel, pacitaxel, and fluoropyrimidine showed a
      better effect on reducing chemotherapy toxicity than cisplatin. Single-drug
      chemotherapy concurrent with radiotherapy, except for nedaplatin, may have no
      advantage on clinical outcomes when compared with cisplatin but showed a better
      effect on reducing chemotherapy toxicity, which could be used as an alternative
      to patients who can not tolerate the side effects of cisplatin. Nedaplatin is
      also effective and safe, and may be highly valuable in clinical applications. 

PMID- 26309519
TI  - Regulatory T cells and IL-17(+) T helper cells enhanced in patients with chronic
      hepatitis B virus infection.
AB  - Hepatitis B is a worldwide infectious disease caused by hepatitis B virus (HBV),
      it leaded to millions of deaths every year, HBV mainly through immune response to
      damage liver cells. The purpose of this study was to judge the value of
      Regulatory T cells (Treg) and IL-17(+) T helper cells (Th17) in different chronic
      HBV infection stages. 96 patients with chronic HBV infection were enrolled and
      selected 33 healthy adults as control. Detected the expression of Treg and Th17
      cells in peripheral blood by flow cytometry and assayed liver function
      simultaneously. Compared to the control group, the expression of Treg (6.80+/
      1.92 vs. 4.42+/-0.97; P<0.0001) and Th17 (6.15+/-4.20 vs. 2.66+/-1.79; P<0.0001)
      cells were both increased and the ratio of Treg/Th17 was significantly decreased
      (1.48+/-0.89 vs. 2.29+/-1.31; P=0.0001) in patients with HBV infection. Spearman
      correlation analysis demonstrated that the level of Treg and Th17 cells were
      associated with liver function. ROC curve analysis found that Treg and Th17 cells
      were suitable for as a screening test for early detection of the disease. In
      conclusion, the expression of Treg and Th17 cells were increased in chronic
      hepatitis B patients and these indicators were independent risk factors to
      hepatitis. 

PMID- 26309521
TI  - Anti-adipogenic and antioxidant effects of the traditional Korean herbal formula
      Samchulgeonbi-tang: an in vitro study.
AB  - AIMS: Here we report in vitro anti-adipogenic and antioxidant effects of
      Samchulgeonbi-tang (SCGBT), a traditional Korean herbal formula. METHODS: 3T3-L1
      preadipocytes were differentiated into adipocytes with or without SCGBT. After
      differentiation, we measured Oil Red O staining, glycerol-3-phosphate
      dehydrogenase (GPDH) activity and leptin production. In addition, its effect on
      scavenging activities of 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)
      (ABTS) and 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radicals in in vitro systems.
      RESULTS: In differentiated 3T3-L1 adipocytes, SCGBT significantly inhibited lipid
      accumulation and triglyceride production, and mediated inactivation of GPDH, a
      major enzyme in the process of adipogenesis. Consistent with this, SCGBT
      stimulation significantly decreased the amount of leptin in 3T3-L1 adipose cells.
      Furthermore, SCGBT enhanced the scavenging activities on ABTS and DPPH radicals.
      The generation of malondialdehyde (MDA) during low-density lipoprotein (LDL)
      oxidation was significantly reduced by SCGBT treatment. Of interest, SCGBT
      extract inhibited reactive oxygen species (ROS) generation in 3T3-L1 adipocytes.
      CONCLUSION: Overall, our findings suggest that SCGBT has the potential for anti
      adipogenic activity and antioxidant properties.

PMID- 26309520
TI  - Overexpression of estrogen receptor beta is a prognostic marker in non-small cell
      lung cancer: a meta-analysis.
AB  - BACKGROUND: Expression of estrogen receptor beta (ERbeta) is a potentially
      interesting prognostic marker and therapeutic target in non-small cell lung
      cancer (NSCLC). Although the expression of ERbeta has been reported to correlate
      with better prognosis of NSCLC in most literatures, some controversies still
      exist. Since the limited patient numbers within independent studies, here we
      performed a meta-analysis to clarify the correlations between ERbeta expression
      and prognosis in NSCLC. MATERIALS AND METHODS: We performed a final analysis of
      2279 patients from 14 evaluable studies for Prognostic Value of overexpression
      ERbeta (up to October 2014). Data from eligible studies were extracted and
      included into meta-analysis using a random effects model. Studies were pooled.
      Summary hazard ratios (HR) were calculated. RESULTS: Our study shows that the
      pooled hazard ratio (HR) of overexpression ERbeta for overall survival in NSCLC
      was 0.78 [95% confidence interval (CI): 0.62-0.98] by univariate analysis and
      1.06 (95% CI: 0.70-1.61) by multivariate analysis. Pooled HR in American and
      Japan was 1.09 (95% CI: 0.95-1.25, P=0.239) from 6 studies reported, however,
      pooled HR was 0.57 (95% CI: 0.46-0.70) outside of American and Japan from 8
      studies reported. Pooled HR was 0.75 (95% CI: 0.60-0.94) from 6 studies reported
      for N-ERbeta and 0.76 (95% CI: 0.51-1.12) from 6 Studies reported for C-ERbeta.
      CONCLUSION: Our results suggested ERbeta was significant associated with good
      overall survival in patients with NSCLC on univariate analysis but not
      multivariate analysis. ERbeta expression is a good prognostic outcome outside of
      American and Japan. Overexpression of N-ERbeta NSCLC patients had better
      survival. Large prospective studies are now needed to confirm the clinical
      utility of ERbeta as an independent prognostic marker.

PMID- 26309522
TI  - Overexpression of vascular endothelial growth factor indicates poor outcomes of
      glioma: a systematic review and meta-analysis.
AB  - BACKGROUND: Accumulated studies have revealed that vascular endothelial growth
      factor (VEGF) plays an essential role in the progression of glioma, but the
      prognostic significance of VEGF expression for patients with glioma remains
      unknown. METHOD AND MATERIAL: A literature search of public databases (PubMed,
      ISI Web of Science, Science Direct, Cochrane Central Register of Controlled
      Trials, Wiley Online Library, China National Knowledge Infrastructure, China
      Biology Medicine disc, Chongqing VIP and Wan Fang Data) was conducted. A meta
      analysis was performed to evaluate the association between the overexpression of
      VEGF and the survival for the glioma patients. Subsequently we evaluated the
      impact of VEGF expression on the pathological grade of glioma. RESULTS: A total
      of 32 articles with 2307 cases contributed to this analysis, of which 31 reported
      overall survival (OS) and 5 reported progression-free survival (PFS). In this
      meta-analysis, VEGF overexpression significantly identified the unfavorable
      outcome on OS (HR = 1.647, 95% CI: 1.324~2.048, P < 0.001, Z = 4.48) but not on
      PFS (HR = 1.021, 95% CI: 0.974~1.070, P = 0.393). Subgroup analyses also revealed
      that high level of VEGF was associated with the poor OS for the patients with
      glioma according to region, case number, specimen type, method to detect VEGF and
      statistical method. Furthermore, the significant correlation was achieved between
      VEGF expression and the pathological grade of glioma (r = 0.307, P < 0.001).
      CONCLUSION: This study suggests that VEGF expression is significantly correlated
      with the glioma progression and may be a valuable prognostic factor on OS for the
      glioma patients.

PMID- 26309523
TI  - Inhibitory effects of preimplantation exposure to bisphenol-A on blastocyst
      development and implantation.
AB  - The effect of preimplantation exposure to bisphenol-A (BPA) on blastocyst
      development and implantation is investigated. Mice were orally administered with
      BPA (200, 400, 600, and 800 mg/kg/day) from Day 0.5 to Day 3.5 of their
      pregnancy. Blastocyst development was examined on Day 4 of pregnancy. With 400
      mg/kg/day BPA, implantation site number and implantation rate significantly
      reduced. With 600 and 800 mg/kg/day BPA, no implantation site was observed. BPA
      at 800 mg/kg/day significantly reduced blastocyst development rate and hatching
      rate. With 400 and 600 mg/kg/day BPA, Blastocyst development rate showed no
      significant difference whereas hatching rate was lower. With 400, 600, and 800
      mg/kg/day BPA, some embryos were detected in the fallopian tube and hatched
      blastocysts showed greatly increased apoptosis level and endothelial nitric oxide
      synthase expression. In summary, high concentration BPA delayed the transfer of
      embryos to the uterus, damaged blastocyst development before implantation, and
      inhibited embryo implantation. 

PMID- 26309524
TI  - Efficacy study of edaravone and acetylcysteine towards bleomycin-induced rat
      pulmonary fibrosis.
AB  - The aim of this study was to investigate the interventional effects of Edaravone
      (EDA) and Acetylcysteine (NAC) towards the Bleomycin (BLM)-induced pulmonary
      fibrosis. 48 Wistar rats were divided into the control group, the BLM group, the
      hormone group, the EDA group, the NAC group and the combination group. After
      performing the BLM intratracheal injection to prepare the pulmonary fibrosis
      model, the rats were administrated EDA, dexamethasone (DEX), NAC and EDA+NAC
      combined intervention, the lung HRCT examination was performed on the 7(th),
      21(st) and 31(st) day. On the 31(st) day, the rats were killed for the detection
      of serum malondialdehyde (MDA) and superoxide dismutase (SOD) contents; the lung
      tissues were performed the HE and Masson staining and determined the
      hydroxyproline content. The rats of the intervention group exhibited mild hypoxic
      phenomenon, with less ground-glass shadow and consolidated shadow than the BLM
      group, the MDA content decreased while the SOD content increased, and the degrees
      of alveolar inflammatory cell infiltration and fibrosis were low. The results of
      the EDA group and the NAC group were similar, and those of the combination group
      were better. EDA could inhibit the BLM-induced pulmonary fibrosis through
      adjusting the oxidant/antioxidant imbalance, with the effect similar to NAC, and
      the combined application of these 2 drugs were much more effective. 

PMID- 26309525
TI  - Meta-analysis on autologous stem cell transplantation in the treatment of limb
      ischemic.
AB  - AIM: Meta-analysis on the effectiveness of the autologous stem cell
      transplantation in curing limb ischemic. METHOD: Consulting papers relate to the
      autologous stem cell transplantation in curing limb ischemic in PubMed, CNKI, Wan
      fang Data and VIP. Based on include and exclude standards, we arrange at least 2
      evaluators sifting these papers separately, doing Quality evaluation and
      information extraction and then cross checking. Negotiate through a third party
      if any disagreement comes out. Review Manager 4.2 is used in Meta-analysis.
      RESULT: Involved 7 papers, all in English version. Patients involved all
      diagnosed as critical limb ischemia (CLI). Results show that no adverse reaction
      occurred during this study. Amputation rate in patients with stem cell group
      treatment is lower than control group (P < 0.05). And no notable difference in
      improving ABI (P > 0.05). CONCLUSIONS: Applying autologous stem cell
      transplantation in curing limb ischemic does not have obviously effectiveness in
      the improvement of ABI of the limb ischemic patients. But it can dramatically
      reduce the rate of amputation. So autologous stem cell transplantation is a good
      and safe choice for patients have no choice but amputation.

PMID- 26309526
TI  - Tri-acryl gelatin microsphere is better than polyvinyl alcohol in the treatment
      of uterine myomas with uterine artery embolization.
AB  - This study is to compare the outcomes of tri-acryl gelatin microspheres (TAGM)
      and polyvinyl alcohol (PVA) in the treatment of uterine myomas with uterine
      artery embolization (UAE). Meta-analysis was performed by electronic literature
      searches from databases including Cochrane Central Register of Controlled Trials,
      PubMed, EMBASE and meta Register of Controlled Trials for studies published prior
      to December 2014. Randomized controlled trials comparing TAGM and PVA treating
      uterine myomas were included in the analysis. Information retrieved from each
      study included study design, number of participants, study settings, patient
      characteristics, sample size, follow-up duration and outcomes. Imaging outcomes
      and clinical outcomes were the main criteria for the evaluation of the included
      studies. Twenty-eight articles published from 1966 to December 2014 were
      retrieved through database searching and other sources. After initial screening
      and assessment, five randomized controlled trials, including 309 women with
      uterine myomas, met the inclusion criteria. In both imaging and clinical
      outcomes, TAGM group showed superior or similar effects than PVA group. The
      results showed more number of patients with significant tumor enhancement,
      greater mean change in tumor volume, greater mean changes in symptom score and
      QOL score in TAGM group compared with PVA group, with significant differences.
      TAGM and PVA groups had similar uterine volume, mean changes in bleeding score
      and pain score. TAGM is better than PVA as an embolic agent in the treatment of
      uterine myomas with UAE. 

PMID- 26309527
TI  - Lung cancer cellular apoptosis induced by recombinant human endostatin gold
      nanoshell-mediated near-infrared thermal therapy.
AB  - AIMS AND BACKGROUND: Endostatin can inhibit tumor endothelial cell proliferation,
      angiogenesis, and growth. We aimed to determine the increase in antitumor
      capabilities of recombinant human endostatin (rhES) when used with a nanocarrier
      system. The effect of gold nanoshell particles of recombinant human endostatin (G
      rhES) with near-infrared (NIR) irradiation on proliferation, inhibition, and
      apoptosis of A549 lung cancer cells was studied. MATERIALS AND METHODS: Gold
      nanoshell particles were prepared. Endostatin was connected with the bond A-U
      through surface modification by bioconjugation of core-shell structured gold
      nanoshells. The drug targeting endostatin and the synthesized G-rhES were
      successfully connected. G-rhES inhibited proliferation of A549 lung cancer cells,
      as detected using tetrazolium colorimetric assay. Cellular apoptosis was measured
      by flow cytometry. Mitochondrial membrane potential was determined using a
      confocal microscope. Morphological changes were studied by atomic force
      microscopy. RESULTS: Under irradiation in the 820 nm NIR, G-rhES significantly
      inhibited the proliferation of A549 lung cancer cells. The underlying mechanism
      may be related to heat-induced apoptosis and cytotoxicity by NIR absorption,
      which kills cells directly, thereby indicating that G-rhES have good
      biocompatibility and pharmacological potency. Characterization of the local
      structure of lung cancer cells showed that G-rhES targeted surface receptors that
      may serve an apoptotic function under NIR exposure. NIR gold nanoshell particles
      showed synergism with endostatin, which may be related to hyperthermia-increased
      cytotoxicity and the apoptotic effect of endostatin. CONCLUSION: These data
      suggest that G-rhES can enhance the inhibition of tumor growth. The new treatment
      strategy of G-rhES combined with thermal therapy may lead to lung cancer
      remission. The potential benefits of G-rhES are being considered for clinical
      evaluation.

PMID- 26309528
TI  - Association between angiotensinogen M235T polymorphism and hypertrophic
      cardiomyopathy.
AB  - BACKGROUND: To investigate the relationship between angiotensinogen (AGT) gene
      M235T polymorphism and hypertrophic cardiomyopathy (HCM) to explore the potential
      role of the AGT polymorphism in HCM. METHODS: PubMed, Embase, OVID, Cochrane
      library, CNKI, Wan Fang Database were searched to identify the studies involving
      AGT M235T polymorphism and HCM. Two authors performed independent literature
      review and study quality assessment using the Newcastle-Ottawa Scale (NOS)
      checklist. A random-effects model was used to calculate the overall combined risk
      estimates. RESULTS: Nine studies involving 887 cases and 1407 controls were
      included in our meta-analysis. No significant associations were found between AGT
      M235T polymorphism and HCM (allele model T vs M: OR = 1.17, 95% CI = 0.95-1.45;
      dominant model TT vs (MM/MT): OR = 1.21, 95% CI = 1.00-1.45; recessive model
      (TT/MT) vs MM: OR = 1.12, 95% CI = 0.87-1.45; heterozygous comparison MT vs MM:
      OR = 1.07, 95% CI = 0.82-1.41; homozygous comparison TT vs MM OR = 1.19, 95% CI =
      0.88-1.61. In subgroup analysis, the significant difference of association
      between AGT M235T polymorphism and HCM existed in Asian and sporadic hypertrophic
      cardiomyopathy (SHCM), but no significant difference was found in Europeans and
      familial hypertrophic cardiomyopathy (FHCM). CONCLUSIONS: There is no association
      between AGT M235T polymorphism and HCM in general populations, but such a
      relationship exists in Asians and SHCM.

PMID- 26309529
TI  - Electrophysiological and histopathological effects of mesenchymal stem cells in
      treatment of experimental rat model of sciatic nerve injury.
AB  - AIM: The aim of this study was to evaluate electrophysiological and
      histopathological effects of mesenchymal stem cells in treatment of sciatic nerve
      injury. MATERIAL AND METHODS: Thirty-two female Spraque-Dawley rat were used in
      this study. Eight rats were used as a reference group in electrophysiological
      analysis for evaluation of non-injured nerve recordings (Control Group). Twenty
      four rats were used for experimental evaluation. Twelve rats were anastomosed
      without treatment with mesenchymal stem cells (Sham Group) and twelve other rats
      were anastomosed and treated with mesenchymal stem cells (Stem Cell Group).
      Surgicel and bioglue were used in anastomosed line in both Groups. Eight weeks
      after the surgery, electrophysiological evaluation of rats was performed and,
      then, rats were decapitated under anesthesia and specimens including sciatic
      nerves and anastomosed line were taken for histopathological evaluation.
      Electromyography and nerve conduction velocity testing and histopathological
      scoring including rate of Wallerian degeneration, and neuroma and scar formation
      were evaluated for both Groups. RESULTS: There were no statistically significant
      differences between Sham and Stem Cell Groups with respect to histopathological
      evaluation. However, nerve conduction velocity showed significant difference
      between groups (P = 0.001). Nerve conduction velocity was significantly improved
      in Stem Cell Group when compared to Sham Group. CONCLUSION: In this study, based
      on nerve conduction velocity data, it was concluded that treatment with
      mesenchymal stem cells during end-to-end anastomosis improves functional
      regeneration.

PMID- 26309530
TI  - Lutein prevents alcohol-induced liver disease in rats by modulating oxidative
      stress and inflammation.
AB  - OBJECTIVE: Oxidative stress and inflammation play an important role in
      pathogenesis of alcohol-induced liver injury. The present study was designed to
      investigate the protective role of Lutein against alcohol-induced liver injury.
      TREATMENT: Wistar rats weighing 150-200 g were divided into 3 groups, control,
      EtOH treatment, Lutein followed by EtOH treatment. Ethanol-treated rats received
      EtOH [5 g/kg body weight] by gavage every 12 hours for a total of 3 doses. For
      Lutein pre-treatment, Lutein at a dose of 40 mg/kg was dissolved in the EtOH and
      gavaged 30 mins before EtOH treatment. METHODS: Oxidative stress markers
      (reactive oxygen species, lipid peroxidation, protein carbonyls and sulfhydryls
      content), liver markers (ALT, AST, ALP and LDH) were determined. Antioxidant
      enzyme activities and its master regulator Nrf-2 expression were analyzed.
      Further, inflammatory proteins NF-kappaB, COX-2, iNOS and inflammatory cytokines
      (TNF-alpha, MCP-1, IL-1beta, IL-6) were analyzed. RESULTS: The results showed
      significant decrease in oxidative stress markers and liver markers in the lutein
      pre-treatment. Lutein treatment down regulated inflammatory proteins and
      cytokines with concomitant up regulation in Nrf-2 levels and antioxidant enzymic
      activities. CONCLUSION: The present study showed that Lutein treatment exerted
      potent antioxidant and anti-inflammatory property and offered significant
      cytoprotection against alcohol-induced liver injury.

PMID- 26309531
TI  - MicroRNA-145 inhibits migration and invasion by down-regulating FSCN1 in lung
      cancer.
AB  - BACKGROUND: The extraordinary invasive capability is a major cause of treatment
      failure and tumor recurrence in lung cancer. Evidence in other cell systems has
      implicated the regulatory role of microRNA-145 in cell motility and invasion,
      which promotes us to investigate the biological functions of miR-145 in lung
      cancer in this regard. RESULTS: We have found that miR-145 is dramatically down
      regulated in clinical specimen of lung cancer and is negatively correlated with
      the tumor pathological grading in the current study. The cells transfected by miR
      145 expression vector have demonstrated retarded cell mobility. Using a
      bioinformatics analysis approach, fascin homolog 1 (FSCN1), actin-binding
      protein, has been identified as the target of miR-145. Over-expression of miR-145
      mimics enhanced protein levels of E-cadherin and fibronectin, indicative of its
      inhibitory role in EMT occurrence. Mechanistic studies showed that miR-145 mimics
      inhibited FSCN1 expression and miR-145 inhibitor enhanced it. Over-expression of
      FSCN1 reversed miR-145-regulated expression of EMT markers, suggesting that FSCN1
      mediated the inhibitory effects of miR-145. Our results revealed a novel
      mechanism that miR-145 inhibits lung cancer cells migration and invasion via
      FSCN1 downregulation. CONCLUSIONS: These results suggest that miR-145 may
      function as anti-migration and anti-invasion influence in lung cancer and
      provides a potential approach for developing miR-145-based therapeutic strategies
      for malignant lung cancer therapy.

PMID- 26309532
TI  - Ultra-structural hair alterations of drug abusers: a scanning electron
      microscopic investigation.
AB  - As drug abuse carries a societal stigma, patients do not often report their
      history of drug abuse to the healthcare providers. However, drug abuse is highly
      co-morbid with a host of other health problems such as psychiatric disorders and
      skin diseases, and majority of individuals with drug use disorders seek treatment
      in the first place for other problems. Therefore, it is very important for
      physicians to be aware of clinical signs and symptoms of drug use. Recently
      diagnostic value of dermatologic tissue alterations associated with drug abuse
      has become a very particular interest because skin changes were reported to be
      the earliest noticeable consequence of drug abuse prompting earlier intervention
      and treatment. Although hair is an annex of skin, alterations on hair structure
      due to drug use have not been demonstrated. This study represents the first
      report on ultra-structural hair alterations of drug abusers. We have investigated
      ultra-structure of the hair samples obtained from 6 cocaine, 6 heroin, 7 cannabis
      and 4 lysergic acid diethylamide (LSD) abusers by scanning electron microscope
      (SEM). SEM analysis of hair samples gave us drug-specific discriminating
      alterations. We suggest that results of this study will make a noteworthy
      contribution to cutaneous alterations associated with drug abuse which are
      regarded as the earliest clinical manifestations, and this SEM approach is a very
      specific and effective tool in the detection of abuse of respective drugs,
      leading early treatment. 

PMID- 26309533
TI  - Soluble costimulatory molecule sTim3 regulates the differentiation of Th1 and Th2
      in patients with unexplained recurrent spontaneous abortion.
AB  - This study is to investigate the mechanism of unexplained recurrent spontaneous
      abortion (URSA). A total of 35 cases of URSA patients (URSA group), 20 cases with
      normal pregnancy (normal pregnancy group) and 20 healthy non-pregnancy candidates
      (healthy control group) were enrolled in this study. Enzyme linked immunosorbent
      assay (ELISA) method was used for detection of serum soluble Tim-3 (sTim3) and
      Galectin-9. Cytokine bead array (CBA) determination method was used to detect IFN
      gamma and IL-4 expression levels. Compared with the healthy control group, sTim-3
      levels in normal pregnancy group and URSA group increased, and URSA group had
      significantly higher sTim-3 levels than normal pregnancy group (P < 0.05).
      Compared with the healthy control group, Galectin-9 levels in normal pregnancy
      group and URSA group also increased. However, the normal pregnancy group had
      significantly higher Galectin-9 level than URSA group (P < 0.05). IFN-gamma
      levels in normal pregnancy group and URSA group were lower than those in healthy
      control group, and IFN-gamma levels in the normal pregnancy group were
      significantly lower than those in URSA group (P < 0.05). Levels of IL-4 in normal
      pregnancy group and URSA groups increased compared with the healthy control
      group, and the IL-4 levels in normal pregnancy group were significantly higher
      than those in URSA group (P < 0.05). Th1/Th2 imbalance, sTim-3 and Galectin-9
      expression increase are found in the patients with URSA, ant this might be
      involved in the regulation of immunity in pregnancy. 

PMID- 26309534
TI  - High dosage of cannabidiol (CBD) alleviates pentylenetetrazole-induced epilepsy
      in rats by exerting an anticonvulsive effect.
AB  - The study was designed to investigate the effect of various concentrations of
      cannabidiol (CBD) in rats with chronic epilepsy. The chronic epilepsy rat model
      was prepared by intraperitoneally injecting pentylenetetrazole to the rats pre
      treated with CBD (10, 20 and 50 mg/kg) for 28 consecutive days. Behavioral
      measurements of convulsion following pentylenetetrazole treatment and
      morphological changes of the hippocampal neurons with hematoxylin and eosin
      staining were used to observe the epileptic behaviour. Immunohistochemistry was
      used to detect the expression levels of glial fibrillary acidic protein and
      inducible nitric oxide synthase (iNOS) in the hippocampus. The mRNA expression of
      N-methyl-D-aspartic acid (NMDA) receptor subunits (NR1 and NR2B) was detected by
      reverse transcription polymerase chain reaction. The results revealed a
      significant decrease in the daily average grade of epileptic seizures on
      treatment with CBD (50 mg/kg). The neuronal loss and astrocyte hyperplasia in the
      hippocampal area were also decreased. CBD treatment did not affect the expression
      of iNOS in the hippocampus; however, the expression of NR1 was decreased
      significantly. Thus, CBD administration inhibited the effect of
      pentylenetetrazole in rats, decreased the astrocytic hyperplasia, decreased
      neuronal damage in the hippocampus caused by seizures and selectively reduced the
      expression of the NR1 subunit of NMDA. Therefore, CBD exhibits an anticonvulsive
      effect in the rats with chronic epilepsy. 

PMID- 26309535
TI  - Normal saline may promote formation of peritoneal adhesions.
AB  - BACKGROUND: Normal saline is commonly used for rinsing the abdominal cavity and
      many surgeons claim that it is not harmful to peritoneum. We found in patients
      treated with laparoscopic surgery, that mean 25% of the instilled fluid is not
      drained and dwells in the abdominal cavity. Therefore we evaluated changes of the
      saline biocompatibility during its dwell in the rats abdominal cavity. METHODS:
      In 10 anesthetized rats normal saline were instilled into the abdominal cavity
      and samples of the dwelling solution were collected every 30 minutes, for 4
      hours. Inflammatory parameters and effect of the collected samples on in vitro
      cultured rats mesothelial cells were studied. RESULTS: Low pH of the saline was
      normalized, but number of cells and % of macrophages and eosinophils, as well as
      elastase activity and MCP-1 and TGF-beta concentration increased, proportionally
      to the dwell time. Fluid samples tested ex-vivo suppressed proliferation of the
      mesothelial cells and induced biphasic (stimulation/inhibition) effect on
      synthesis of MCP-1 in these cells. Similar pattern of release was observed for
      TF, whereas synthesis of t-PA in the mesothelial cells was strongly suppressed.
      CONCLUSIONS: Mesothelial cells exposed in vivo to normal saline dwelling in the
      abdominal cavity acquire properties which may accelerate formation of the
      peritoneal adhesions.

PMID- 26309536
TI  - MicroRNA-21 regulates non-small cell lung cancer cell proliferation by affecting
      cell apoptosis via COX-19.
AB  - AIMS: This study is to investigate the regulatory effect of microRNA-21 (miR-21)
      on bone metastasis of non-small cell lung cancer (NSCLC). METHODS: In this study,
      18 patients were diagnosed with vertebral column metastasis of NSCLC. MiR-21 or
      small interfering RNAs were transfected into H2170 cells using Lipofectamine
      2000. Real-time PCR was performed to detect miR-21 expression. Western blotting
      was used to measure the expression of COX-19 protein. Enzymatic activity tests
      were performed to measure the activity of cytochrome C oxidase. Flow cytometry
      was used to monitor changes in cell apoptotic rate. MTT assay was used to
      determine the capability of cell proliferation. RESULTS: Bone metastasis of NSCLC
      enhanced the levels of miR-21 in NSCLC patients. Proliferation capability of
      cells with high expression of miR-21 was greater than that of cells with the
      inhibition of miR-21 expression. High expression of miR-21 promoted cell
      proliferation by inhibiting cell apoptosis. COX-19 was a key factor in the
      inhibition of apoptosis by miR-21. Inhibition of COX-19 expression reduced cell
      proliferation by enhancing cell apoptosis. CONCLUSIONS: This study demonstrates
      that inhibition of miRNA-21 suppresses NSCLC cell proliferation by promoting cell
      apoptosis via the decrease of COX-19 expression.

PMID- 26309537
TI  - Pre-B-cell colony enhancing factor (PBEF) increases endothelial permeability in
      hypoxia/re-oxygenation model.
AB  - OBJECTIVE: This study aims to explore the relationship between PBEF and VEGF and
      p-MLC and the mechanism of PBEF increasing permeability of endothelial cells in
      hypoxia/re-oxygenation. METHODS: Hypoxia/re-oxygenation model was established and
      PBEF siRNA was synthesized. According to the different HUVEC treatment, it can be
      divided into normal control group, PBEF siRNA group; hypoxia (20 hours) and re
      oxygenation (3 h) group, hypoxia (20 h) and re-oxygenation (6 h) group, hypoxia
      (20 h) and re-oxygenation (9 hours) group, hypoxia (20 h)/re-oxygenation (12 h).
      The expressions of PBEF, VEGF and p-MLC were tested by RT-PCR and Western blot.
      RESULTS: The mRNA and protein expression of PBEF in PBEF siRNA group were
      significantly lower compared to liposome group and the negative controls (P <
      0.05). The expression of PBEF protein in hypoxia/re-oxygenation group was
      significantly higher than the normal control group. It increased in the 3 h of re
      oxygenation group, peaked at 9 h, until 12 h started to decline (P < 0.05). When
      the PBEF gene was knockdown, the expression of VEGF and p-MLC in hypoxia and re
      oxygenation are significantly lower. CONCLUSIONS: PBEF siRNA can effectively
      inhibit the expression of PBEF in endothelial cells. The expression of PBEF, VEGF
      and p-MLC were significantly higher in endothelial cell after Hypoxia/re
      oxygenation. PBEF may change the permeability of endothelial cells by regulating
      the expression of VEGF and the phosphorylation of MLC.

PMID- 26309538
TI  - Efficacy comparison between manual small incision cataract surgery and
      phacoemulsification in cataract patients: a meta-analysis.
AB  - OBJECTIVE: Systematic review of manual small incision cataract surgery (MSICS)
      and phacoemulsification (PHACO) on the postoperative visual quality and surgical
      complications. METHODS: Relevant literatures on clinical efficacy of PHACO and
      MSICS were included by retrieving in Medline, PubMed, Chinese Biomedical
      Literature Database (CBM) and Chinese Academic Journal (CNKI) databases. Meta
      analysis was conducted by RevMan5.0 software with OR and its 95% CI for the
      effect size. RESULTS: A total of ten documents were included in the study.
      Uncorrected visual acuity 1 week after surgery (OR = 0.84, 95% CI: 0.67 ~ 1.06,
      P=0.15), post-operative capsular rupture (OR = 1.07, 95% CI: 0.73~1.58, P=0.72),
      and corneal edema (OR = 0.90, 95% CI: 0.70~1.16, P=0.42) between MSICS and PHACO
      showed no statistical difference (P > 0.05). CONCLUSION: Clinical efficacy and
      complications of MSICS was similar tothat of PHACO.

PMID- 26309539
TI  - Apigenin attenuates acute myocardial infarction of rats via the inhibitions of
      matrix metalloprotease-9 and inflammatory reactions.
AB  - Acute myocardial infarction (AMI) is the myocardial necrosis caused by coronary
      artery acute and persistent ischemia and hypoxia. Matrix metalloprotease-9 (MMP
      9) plays an important role in a series of process of occurrence and development
      of AMI. Inflammatory reaction plays the key role in all kinds of damage factors
      in AMI. Apigenin (API) has effectively restrained the activity of MMP-9, anti
      inflammatory and hepatic fat oxidizing properties. API significantly improved AMI
      of rats through inhibiting MMP-9 and inflammatory reactions in a few recent
      studies. Our investigation detected the infarct size of AMI rats, casein kinase
      (CK), the MB isoenzyme of creatine kinase (CK-MB) and lactate dehydrogenase (LDH)
      and cardiac troponin T (cTnT) activities in AMI rats were also analyzed with
      commercial kits. Additionally, Nuclear factor kappa B (NF-kappaB), tumor necrosis
      factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6)
      levels of whole bloods of AMI rats were also detected using commercial kits.
      Next, MMP-9 protein of cardiac in AMI rats was measured with gelatin zymography
      assays. Finally, caspase-3 and caspase-9 activities in AMI rats were analyzed
      with commercial kits. In the present study, our work indicated API might
      significantly reduce the infarction size of AMI rat. It was shown that the
      treatment of API could decrease the expression of MMP-9 level and reduce the
      activities of NF-kappaB, TNF-alpha, IL-1beta and IL-6 in AMI rats. Next, API
      treatment could reduce caspase-3 and caspase-9 activities and decrease cellular
      apoptosis of AMI rats. Our findings concluded that API ameliorates acute
      myocardial infarction of rats via inhibiting MMP-9 and inflammatory reactions. 

PMID- 26309540
TI  - Palliation of malignant esophageal obstruction and fistulas with covered self
      expandable metallic stents: assessment of a simple fluroscopic method.
AB  - PURPOSE: To introduce a convenient, quick and effective way to place self
      expandable metal stents (SEMSs) to relieve dysphagia and fistula caused by
      esophageal carcinoma. MATERIALS AND METHODS: A consecutive series of 36 patients
      (25 men, 11 women), aged 38-82 years (median, 52.7 years) underwent stent
      placement using a 7F long sheath of 55 cm and fully covered SEMS under local
      anesthesia with fluoroscopic control. RESULTS: Stent placement was successful in
      all patients. Swallowing improved from mean dysphagia score 3.44 +/- 0.50 to
      score 0.69 +/- 0.71 (P = 0.000). There were no clinically significant
      complications during and after the deployment of stents. Migration was noted in 4
      patients. Restenting was needed in 3 patients. Removal was needed in 2 patients.
      Mean survival following stenting was 134.14 d. CONCLUSIONS: SEMSs provide rapid,
      safe and effective relief of dysphagia and fistula. Using the 7F long sheath of
      55 cm could make the procedure easy, quick and safe.

PMID- 26309541
TI  - Insights into the molecular mechanisms of methylmalonic acidemia using microarray
      technology.
AB  - Methylmalonic acidemia (MMA) is widely considered as an autosomal recessive
      metabolic disorder that results in accumulation of high levels of methylmalonic
      acid and eventually brain damage. This study aims to investigate the effects of
      methylmalonic acid on neurons and analyze various gene expression profiles in rat
      cortical neurons treated with methylmalonic acid in order to understand the
      effects of MMA. High concentrations of methylmalonic acid could significantly
      alter the morphology of rat cortical neurons, attenuate cell viability and
      aggravate cell apoptosis. Moreover, 564 differentially expressed genes were
      identified by microarray analysis. A considerable number of these genes were
      apoptosis-related genes. Enrichment analysis of the apoptosis-related genes
      revealed that the MAPK and p53 signaling pathways may be involved in the
      pathogenesis of MMA. Our results together reveal that methylmalonic acid plays a
      critical role in neuron damage and that the MAPK and p53 signaling pathways may
      be involved in the mechanism of MMA. 

PMID- 26309542
TI  - Association between the TNF-alpha G-308A polymorphism and risk of ischemic heart
      disease: a meta-analysis.
AB  - BACKGROUND: The role of the tumor necrosis factor-alpha (TNF-alpha) G-308A
      polymorphism in the risk of ischemic heart disease (IHD) has been controversial
      in recent decades. A substantial number of newly-published studies concerning the
      association between the TNF-alpha polymorphism and IHD risk have emerged after
      the publication of the latest meta-analysis. Therefore, we conducted an updated
      meta-analysis to further investigate the influence of this polymorphism on IHD.
      METHODS: Electronic databases (PubMed, Embase, CNKI, and Wanfang) were
      systematically searched to identify all relevant papers published before
      September 25(th), 2014. The quality of all eligible studies was assessed. Pooled
      odds ratios (ORs) with 95% confidence intervals (CIs) of all studies and high
      quality studies were assessed by the fixed/random-effects model in Review Manager
      5.0.25 and STATA 10.0. Heterogeneity and publication bias were detected;
      sensitivity analysis was conducted. RESULTS: Data from 36 studies were recorded
      after study selection and exclusion. Under the dominant model, the results of
      pooled analysis of high-quality studies suggested that the G-308A polymorphism
      was associated with an increased risk of IHD in total population (P = 0.02, OR =
      1.13, 95% CI = 1.02-1.24, P heterogeneity = 0.009, I(2) = 45%). No significant
      result was obtained in Asians, Caucasians, or Indians. CONCLUSION: The TNF-alpha 
      308A allele is probably associated with an increased risk of IHD in total
      population, but to further identify this association, more high quality studies
      in Indians and Africans are merited.

PMID- 26309543
TI  - Acid-suppressive medications and risk of fracture: an updated meta-analysis.
AB  - BACKGROUND: Acid-suppressive medications are widely used for the management of
      acid-related disorders. It has been reported that acid-suppressive medication
      users were at increased risk of fracture, but such an association was
      inconsistent among observational studies. The purpose of our analysis was to
      assess the relationship between use of antacid drugs and fracture risk. METHODS:
      We systematically searched electronic database and manually examined the
      reference lists of previous reviews for potentially eligible studies. Given the
      heterogeneity across studies, random effects models were used to calculate
      summary estimates. Subgroup analysis and sensitivity analysis were conducted to
      explore the potential heterogeneity. RESULTS: 18 studies met our inclusion
      criteria. PPI and H2RA were associated with increased risk of hip fracture, with
      substantial heterogeneity (PPI: 1.216, 1.134-1.304, I(2)=71.3%; H2RA: 1.128,
      1.022-1.245, I(2)=72.1%). High risk of spine fracture was observed in PPI users
      (1.216, 95% CI: 1.134-1.304) but not H2RA users. When considering 5 studies
      conducted among postmenopausal women, the RR was 1.376, (95% CI: 1.043-1.816)
      with modest heterogeneity (I(2)=57.7%). Subgroup analysis and sensitivity
      analysis found consistent association between hip fracture risk and PPI use but
      not H2RA use. Positive association for H2RA use lost its significance when
      considering case-control studies and European studies. CONCLUSION: Results of
      this updated meta-analysis provided evidence to support that acid-suppressive
      medications were associated with increased risk of fracture, especially hip
      fracture.

PMID- 26309544
TI  - Confocal laser endoscopy in the diagnosis for abdominal lymph node metastasis of
      gastric cancer.
AB  - Confocal laser endoscopy (CLE) diagnostic criteria for lymph node metastasis of
      gastric cancer was established and evaluated to provide a basis for CLE clinical
      application in the diagnosis of abdominal lymph node metastasis. CLE scanning
      (surface scanning and sectional scanning) and pathology examination were
      conducted in gastric cancer tissues and lymph nodes of 5 cases. Characteristics
      of lymphatic metastasis in CLE imaging were observed and summarized in
      combination with pathology. The diagnostic criteria were corroborated in 124
      lymph nodes of another 14 cases and CLE detection time needed for diagnosis was
      recorded. The CLE diagnostic criteria were tested and evaluated, and the effect
      of lymph node size on the diagnosis accuracy was determined. All the 19
      participants were confirmed as gastric cancer. Sectional scanning can get
      comprehensive observation for internal structures of lymph nodes, in which
      abnormal large heterocyst appeared with special structural changes. CLE scanning
      could detect 88.75% of the positive metastasis and 68.18% of the negative
      metastasis examined by the pathology methods based on the established CLE
      diagnostic criteria. In comparison with pathological diagnosis, specificity,
      sensitivity and accuracy of CLE diagnosis were 88.75%, 68.18% and 81.45%,
      respectively. Accuracies of CLE diagnosis on the lymph nodes grouped by size were
      85.29%, 77.78% and 88.89%, respectively, with no significant difference between
      groups (P > 0.05). Complete internal structures of lymph nodes can be observed
      clearly by CLE sectional scanning. The size of lymph nodes had no effects on
      diagnosis accuracy. CLE shows better sensitivity and specificity than traditional
      pathological diagnosis. 

PMID- 26309545
TI  - Cytochrome P450 2E1 RsaI/PstI polymorphism is associated with urologic cancer
      risk: evidence from a meta-analysis.
AB  - Cytochrome P450 2E1 (CYP2E1) is involved in the metabolic activation of various
      carcinogens. CYP2E1 RsaI/PstI polymorphism has been identified in urologic cancer
      patients, while studies of the polymorphism have shown inconclusive trends in the
      risk of urologic cancers. Therefore, we performed this systematic review to
      provide a complete picture and conducted a meta-analysis to derive a precise
      estimation. We searched PubMed, Embase and Web of Science to identify eligible
      studies up to December 15, 2014. 12 studies with 2712 cases and 2977 controls
      were included in the meta-analysis.The odds ratio with a 95% confidence interval
      was used to assess the strength of associations. We observed that the c2 allele
      of CYP2E1 RsaI/PstI polymorphism was associated with a decreased risk of urologic
      cancer under all genetic models (c2 vs. c1: OR = 0.742, 95% CI = 0.659-0.835);
      c2c2 vs. c1c1: OR = 0.516, 95% CI = 0.357-0.745; c1c2 vs. c1c1: OR = 0.748, 95%
      CI = 0.748 (0.648-0.863; c2c2 + c1c2 vs. c1c1: OR = 0.722, 95% CI = 0.629-0.829;
      c2c2 vs. c1c1 + c1c2: OR = 0.578, 95% CI = 0.401-0.832). In the subgroup analysis
      by cancer type, statistically significant associations were found in urothelial
      cancer in all genetic models. When stratified by ethnicity, a same trend was also
      indicated in Asians in all genetic models.To conclude, our results support the
      conclusion that the CYP2E1 RsaI/PstI polymorphism may be associated with urologic
      cancer susceptibility. The c2 allele is a low-penetrance risk factor for urologic
      cancer development. 

PMID- 26309546
TI  - Molecular imaging of stem cells for the treatment of acute myocardial infarction.
AB  - Stem cell therapy has a unique potential and promises hope for the treatment of
      acute myocardial infarction. Preclinical studies have identified barriers to
      clinical translation, one of which involves the monitoring of transplanted cells
      and the elucidation of their fates in vivo. Molecular imaging may help the
      solutions for these challenges. In this review, we illustrate the mechanisms by
      which molecular imaging enables insights into and the development of stem cell
      therapy. 

PMID- 26309547
TI  - Curcumin inhibits lung cancer invasion and metastasis by attenuating GLUT1/MT1
      MMP/MMP2 pathway.
AB  - Glucose transporter (GLUT) 1 is found highly expressed in malignant tumors and
      considered a mediator inducing cancer metastasis. Curcumin is a natural product
      which exerts anti-invasion and metastasis effects in cancer. This study aimed at
      evaluating whether attenuating GLUT1 was involved in curcumin's anti-invasion and
      metastasis effects. In the in vitro part, constricted pcDNA3.1-GLUT1 vector was
      transfected into A549 cells. MTT assay was used to assess the curcumin's effects
      on proliferation in lung cancer A549 cells. Transwell assay was used to evaluate
      the anti-invasion effect of curcumin on A549 cells. Real-time PCR and Western
      blotting were employed to examine the expression levels of GLUT1, membrane type 1
      MMP (MT1-MMP) and matrix metalloproteinase (MMP) 2 in curcumin- incubated A549
      cells. In the in vivo part, tumor weight and metastatic rate were assessed in
      nude mice bearing untransfected, empty vector transfected and pcDNA3.1-GLUT1
      transfected A549 cells originated tumors. In this study, we found that curcumin
      began to show significant cytotoxicity against proliferation effect at 45
      MUmol/L. Curcumin inhibited invasion and expressions of GLUT1, MT1-MMP and MMP2
      untransfected A549 cells in a concentration-dependent manner. pcDNA3.1-GLUT1
      transfected A549 cells exhibited resistance to curcumin's anti-invasion effect by
      up-regulating expressions of GLUT2, MT1-MMP and MMP2. Furthermore, curcumin
      failed to decrease the metastatic rate in nude mice bearing pcDNA3.1-GLUT1
      transfected A549 cells originated tumors. These results suggested that curcumin
      inhibit lung cancer invasion and metastasis by attenuating GLUT1/MT1-MMP/MMP2
      pathway. 

PMID- 26309548
TI  - Baicalin induces apoptosis in hepatic cancer cells in vitro and suppresses tumor
      growth in vivo.
AB  - Baicalin is a flavonoid glycoside extracted from a kind of traditional Chinese
      drug, Scutellaria baicalensis, and possesses multiple pharmacological activities.
      The present study was designed to investigate the effects and mechanisms of
      baicalin against hepatic cancer cell growth and survival. We found that baicalin
      inhibited the viability and proliferation of two widely used hepatic cancer cell
      lines, Hep G2 and SMMC-7721 cells, in a dose-dependent manner. Cell cycle
      analysis revealed an increase in the S-phase cell population following 48 h
      exposure to baicalin. The expression levels of Cyclin A, CDK2, and Cyclin D1 were
      downregulated by baicalin treatment. Moreover, baicalin induced apoptotic cell
      death in Hep G2 and SMMC-7721 cells, which was accompanied by upregulation of
      Bax, downregulation of Bcl-2, and cleavages of Caspase-9, Caspase-3, and PARP.
      Furthermore, baicalin significantly inhibited the growth of xenografts in nude
      mice. In conclusion, we demonstrated for the first time that baicalin inhibited
      hepatic cancer cell growth and survival both in vitro and in vivo, suggesting
      that baicalin may be a potential phytochemical flavonoid for hepatic cancer
      therapy. 

PMID- 26309549
TI  - Effects of cold light bleaching on the color stability of composite resins.
AB  - To evaluate the effects of cold light bleaching on the color stability of four
      restorations using a thermocycling stain challenge. 160 specimens (10 mm in
      diameter and 2 mm thick) were fabricated from 4 composite resins (Gradia Direct
      A, Z350XT, Premisa, and Precis) and divided into 4 subgroups. Color was assessed
      according to the CIEL*a*b* color scale at baseline, after the first cycle of
      bleaching, after thermocycling stain challenges, and after the second cycle of
      bleaching. Mean values were compared using three-way analysis of variance, and
      multiple comparisons of the mean values were performed using the Tukey-Kramer
      test. All groups showed significant color changes after stain challenge, the
      color change was more significant in Gradia Direct and Z350XT than in Premisa and
      Precis. After the second cycle of bleaching, color mostly recovered to its
      original values. The color stability of Gradia Direct and Z350XT was inferior to
      that of Premisa and Precis. The discoloration of composite resin materials can be
      partly removed after cold light bleaching. 

PMID- 26309550
TI  - Association of hOGG1 Ser326Cys polymorphism with susceptibility to hepatocellular
      carcinoma.
AB  - BACKGROUND: Since, the relationship between hOGG1 Ser326Cys polymorphism and HCC
      was inconsistent in the recent literatures. The present meta-analysis based on
      previous studies was to obtain precise estimation on the issue. METHODS: A
      computer search was carried out from PubMed, CBM and EMBASE databases. A total of
      nine case-control publications with 2583 HCC patients and 2271 controls were
      included in the meta-analysis. Pooled odds ratios (ORs) and 95% confidence
      intervals (CIs) were calculated to evaluate the relationship of Ser326Cys
      polymorphism and HCC susceptibility. Z test was used to assess the significance
      of pooled OR. The fixed-effect model or random-effect model was employed
      according to heterogeneity. RESULTS: Overall, hOGG1 Ser326Cys polymorphism was in
      relation with increased risk for HCC under the following genetic models: GG
      versus CC: OR=2.51, 95% CI=1.67-3.78; GG versus CG + CC: OR=2.27, 95% CI=1.57
      3.30; GG + CG versus CC: OR=1.13, 95% CI=1.03-1.24. The subgroup analysis by
      ethnicity suggested that high risk for HCC was observed in Asians with GG and GG
      + CG genotype (GG versus CC: OR=2.17, 95% CI=1.49-3.17; GG versus CG + CC:
      OR=1.96, 95% CI=1.41-2.73; GG + CG versus CC: OR=1.13, 95% CI=1.03-1.25). For
      subgroup analysis based on source of control, GG genotype of Ser326Cys was
      significantly associated with HCC risk in hospital-based (HB) controls (GG versus
      CC: OR=2.31, 95% CI=1.50-3.56; GG versus CG + CC: OR=2.17, 95% CI=1.44-3.28), as
      well as in population-based (PB) models (GG vs. CC: OR=2.80, 95% CI=1.16-6.77; GG
      versus CG + CC: OR=2.39, 95% CI=1.08-5.30). CONCLUSIONS: According to the
      results, hOGG1 Ser326Cys polymorphism was associated with increased risk of HCC.

PMID- 26309551
TI  - Association of APOA5 T1131C polymorphism and risk of coronary artery disease.
AB  - AIMS: Our research aimed to investigate the relationship between Apolipoprotein
      A5 (APOA5) T1131C polymorphism and the risk of coronary artery disease (CAD).
      METHODS: We searched the relevant articles in databases and 25 ones were chosen.
      The association between APOA5 T1131C polymorphism and CAD risk was evaluated
      using odds ratios (ORs) and 95% confidence intervals (95% CIs). The fixed-effect
      model or random-effect model was applied according to the heterogeneity analysis.
      RESULTS: Overall, significant association between CAD risk and APOA5 T1131C
      polymorphism was found (CC vs. TT: OR=1.47, 95% CI=1.22-1.78; CC+TC vs. TT:
      OR=1.13, 95% CI=1.07-1.20; CC vs. TT+TC: OR=1.37, 95% CI=1.13-1.66; allele C vs.
      allele T: OR=1.17, 95% CI=1.09-1.25; TC vs. TT: OR=1.12, 95% CI=1.06-1.20). In
      the ethnicity subgroup analysis, risk of CAD was observed in all genotypes among
      Asians (CC vs. TT: OR=1.40, 95% CI=1.17-1.68; CC+TC vs. TT: OR=1.13, 95% CI=1.06
      1.20; CC vs. TT+TC: OR=1.30, 95% CI=1.08-1.56; allele C vs. allele T: OR=1.15,
      95% CI=1.08-1.24; TC vs. TT: OR=1.13, 95% CI=1.06-1.21), While in Caucasians, the
      similar association was only found in several genotypes. In the subgroup analysis
      by source of control, we found that APOA5 T1131C polymorphism could increase the
      risk of CAD in population-based (PB) genetic group (CC vs. TT: OR=1.54, 95%
      CI=1.29-1.84; CC+TC vs. TT: OR=1.15, 95% CI=1.08-1.23; CC vs. TT+TC: OR=1.45, 95%
      CI=1.19-1.76; allele C vs. allele T: OR=1.19, 95% CI=1.12-1.25; TC vs. TT:
      OR=1.14, 95% CI=1.06-1.22). There was no correlation found in hospital-based (HB)
      genetic group yet. CONCLUSION: APOA5 T1131C polymorphism might be significantly
      associated with susceptibility to CAD.

PMID- 26309552
TI  - Interleukin-6 C-572G gene polymorphism and coronary artery disease in Asian: a
      meta-analysis of 2511 subjects.
AB  - The interleukin-6 (IL-6) C-572G gene polymorphism has been suggested to be
      associated with the increased coronary artery disease (CAD) risk, but the study
      results are still debatable. To explore the association between IL-6 C-572G gene
      polymorphism and CAD in the Asian population, the current meta-analysis involving
      2511 subjects from 7 separate studies was conducted. The combined odds ratio
      (ORs) for the association between IL-6 C-572G gene polymorphism and CAD and their
      corresponding 95% confidence intervals (95% CIs) were assessed by random or fixed
      effect model. A significant association between IL-6 C-572G gene polymorphism and
      CAD was found in the Asian population under an allelic (OR: 1.50, 95% CI: 1.30
      1.71, P<0.00001), recessive (OR: 2.221, 95% CI: 1.444-3.417, P=1.0*10(-10))
      dominant (OR: 1.313, 95% CI: 1.188-1.451, P=1.0*10(-10)), homozygous (OR: 2.454,
      95% CI: 1.606-3.751, P=1.0*10(-10)), heterozygous (OR: 3.01, 95% CI:1.99-4.55,
      P<0.00001) and additive genetic models (OR: 1.372, 95% CI: 1.231-1.528, P=1.0*10(
      10)). In the Asian population, the IL-6 C-572G gene polymorphism was indicated to
      be correlated with CAD susceptibility. The carriers of -572G allele might be
      predisposed to CAD risk. 

PMID- 26309553
TI  - TCM matrine inducescell arrest and apoptosis with recovery expression of the
      hepato-specific miR122a in human hepatocellular carcinomaHep G2cell line.
AB  - Hepatocellular carcinoma (HCC) accounts for 80% to 90% of liver cancers and it is
      one of the most prevalent carcinomas throughout the world. Traditional
      chemotherapy is often developed chemoresistance HCC patients.Matrine is an active
      component oftraditional Chinese medicine (TCM) and is a promising alternative HCC
      drug. In this study, the therapeutic effects and the underlying molecular
      mechanisms of matrine on the human HCC cell lineHep G2 were investigated. High
      dosage of matrine (1.0 mg/mL) could significantly (P < 0.05) inhibit cell
      proliferation by 48.39 +/- 3.32%, under which cell shrinkage and disruption were
      observed. Flow cytometry assay showed that the proportion of G1/G0 cells
      significantly increased, while that of S and G2/M cells significantly decreased
      after treatment of matrinefor 48 h. These results indicated that cell arrest by
      matrine appeared. Up-regulation of the hepato-specific miR122a followed by down
      expression of its targetcyclin G1 (CG1) gene by low concentration of matrine (0.2
      mg/mL) was detected using was observed using quantitative real-time PCR,
      immunohistochemistry (IHC) and western blot assays. In conclusion,
      matrineinducescell arrest and apoptosis with recovery expression of the hepato
      specific miR122a in human hepatocellular carcinoma Hep G2 cell line. 

PMID- 26309554
TI  - Tangzhining exhibits a protective effect against cognitive dysfunction in
      diabetic rats.
AB  - Previous studies have suggested that diabetes significantly impairs the cognitive
      function. Tangzhining (TZN), as a kind of Traditional Chinese Medicine (TCM), has
      been widely used to treat diabetes in China. However, the effect of TZN on
      treatment of diabetes-induced learning and memory deficits has not been well
      documented. The present study was to investigate the effect of TZN on diabetes
      induced learning and memory deficits and delineate the underlying molecular
      mechanism. Diabetic rats were randomly grouped and treated with various doses of
      TZN (0.47, 0.94 and 1.4 g/kg) by intraperitoneal injection. Using the Morris
      water maze, TZN treatment (0.94 g/kg and 1.4 g/kg) reduced markedly the escape
      latency and path length of diabetic rats. The morphological changes of pyramidal
      cells in hippocampus of diabetic rats were apparently reversed and improved by
      TZN treatment, in comparison with that in diabetic rats without TZN treatment.
      Moreover, the results of Western blot analysis showed that TZN treatment
      significantly increased the protein expression of glutamic acid decarboxylase
      (GAD) and excitatory amino acid carrier 1 (EAAC1) in hippocampus of diabetic
      rats. Furthermore, TZN treatment increased the protein expression of N-methyl-D
      aspartic acid (NMDA) receptor subunits including NR1 and NR2B. Taken together,
      our data suggest that TZN sustains the balance between glutamate (Glu) and GABA
      by regulating GAD and EAAC1, and maintains the NMDA receptors activity for
      learning and memory function through regulating the subunits NR1 and NR2B. 

PMID- 26309555
TI  - Gene expression profiling by mRNA array reveals different pattern in Chinese
      glioblastoma patients between Uygur and Han populations.
AB  - OBJECTIVE: To identify differentially expressed genes in Chinese glioblastoma
      patients of Uygur and Han populations, and investigate their potential clinical
      value for pathogenesis determination and progress prediction. METHODS: Gene
      expression profiling was obtained from three patients of each Uygur and Han
      nationalities, respectively, by mRNA expression array. Data were processed by the
      GenomeStudio software and language R of the Lumi package, followed by GO (Gene
      Ontology) term and KEGG pathway annotation analysis by the Web Gestalt software.
      RESULTS: The comparative analysis of genome-scale gene expression in
      glioblastomas revealed 1,475 differentially expressed genes, with 669 and 807
      genes up-regulated and down-regulated, respectively. These included the STRC
      gene, which has two transcripts, one up-regulated and one down-regulated. GO term
      analysis suggested that 1,175 out of 1,475 key genes were involved in small
      GTPase mediated signal transduction, Ras protein signal transduction, bioprocess
      of neuronal response regulation, and central nervous system myelination. The KEGG
      pathway enrichment analysis showed that the differentially expressed genes were
      covered by 28 signaling pathways associated with tumorigenesis, including
      metabolic pathways, tumor suppressor pathways, MAP kinase signaling pathways, TGF
      beta signaling pathway, neurotrophin signaling pathways, and mTOR signaling
      pathway. CONCLUSION: The comparative study of gene expression profiling in
      glioblastomas between Uygur and Han nationalities revealed differentially
      expressed genes, whose functions and expression localization were analyzed by GO
      term analysis and KEGG pathway enrichment analysis. Different pathogenesis
      mechanisms were proposed for glioblastomas in Chinese patients of Uygur and Han
      nationalities from a molecular biology perspective.

PMID- 26309556
TI  - Lovastatin induces neuroprotection by inhibiting inflammatory cytokines in 6
      hydroxydopamine treated microglia cells.
AB  - PURPOSE/AIM: This study aims to investigate the impact of lovastatin on
      neuroinflammation in 6-OHDA-treated microglia cells. MATERIALS AND METHODS: 6
      Hydroxydopamine (6-OHDA)-treated microglia cells were used to investigate the
      neuroprotective nature of lovastatin. After incubation with 6-OHDA and/or
      lovastatin for 24 h, test kits were used to detect the levels of LDH and
      glutamate, which were released from PC12 cells exposed to different culture
      media. The mRNA levels of TNF-alpha, IL-6 and IL-1beta were determined by RT-PCR
      and the protein levels were analyzed by Western blot. RESULTS: LDH and glutamate
      levels in 6-OHDA-incubated PC12 cells increased, when compared with those in the
      controls, while incubation with lovastatin inhibited this elevation. The
      expression levels of TNF-alpha IL-6 and IL-1beta were significantly upregulated
      after treatment with 6-OHDA. The 6-OHDA-stimulated mRNA and protein levels of TNF
      alpha IL-6 and IL-1beta were reduced by lovastatin. CONCLUSIONS: Our results
      suggest that Lovastatin is able to induce neuroprotection by inhibiting
      inflammatory cytokines. The data provide direct evidence of the potential
      application of lovastatin for the treatment of neuroinflammatory diseases.

PMID- 26309557
TI  - Decreasing cartilage damage in a rat model of osteoarthritis by intra-articular
      injection of deoxycholic acid.
AB  - BACKGROUND: The aim of this experimental study was to evaluate the effect of
      intra-articular injection of Deoxycholic acid (DCA) on articular cartilage and
      subchondral bone following induction of knee Osteoarthritis (OA) in a rat model.
      METHODS: Twenty-four Sprague Dawley rats were randomized divided into 4 groups (n
      = 6). Eighteen of the 24 rats underwent surgical destabilization of the medial
      meniscus on the right knee joints to induce OA, were divided into 3 groups: DCA
      30 mg/kg group, DCA 120 mg/kg group and OA group. The rats in DCA-treated groups
      were given intra-articular injections of DCA (30 mg/kg or 120 mg/kg) in the
      operated knees once per 3 days for 42 days. The rats in OA group given intra
      articular injections of vehicle alone in the operated knees under the same
      conditions. The remaining 6 rats (sham-operation group) received sham operations
      on the right knee joints. 45 days postoperatively, all of the animals were
      euthanized for macroscopic, histological and radiographic analysis to evaluate
      the effect of DCA on OA and to determine its potential mechanisms. RESULTS: The
      results showed that DCA attenuated the severity of OA by reducing macroscopic
      observation sores for femoral condyles and histological sores for articular
      cartilage. DCA also significantly decreased bone destruction and erosion of joint
      evaluated by radiographic examination. Furthermore, DCA could markedly reduce the
      release of MMP-1, MMP-3 and IL-1beta in serum. CONCLUSIONS: Intra-articular
      injection of DCA is beneficial for knee OA. It might repair and protect OA
      cartilage by delaying cartilage degeneration and impairing the function of
      inflammatory mediators. These findings highlight DCA might be a useful
      therapeutic agent for OA.

PMID- 26309558
TI  - Mechanical analysis on individualized finite element of temporal-mandibular joint
      under overlarge jaw opening status.
AB  - BACKGROUND: Analyze the stress status of temporal-mandibular joint (TMJ) of a
      healthy volunteer under the overlarge jaw opening status through the finite
      element method, with the purpose of clarifying the loading features of each
      structure in the joint area, and achieving further understanding of the
      pathogenesis of the temporomandibular disorders (TMD). METHODS: Collect the CBCT
      and MRI data of a volunteer respectively under the maximum jaw opening, establish
      the finite element model (FEM) of TMJ under the maximum jaw opening status
      through a series of software, image segmentation, rectification, meshing,
      material evaluation and other related processing, simulate the mechanical
      environment of this joint area under this status, and analyze the stress status
      of the articular disc, condyle cartilage, and condyle process. RESULTS: Based on
      CT and MRI image data, build 3D model and FEM of TMJ, fully simulate the
      mechanical environment under the large jaw opening status, and calculate the
      stress value of the articular disc, condyle process and condylar cartilage.
      CONCLUSIONS: This research result reminds us that the normal people's articular
      disc are easy to generate stress concentration under large jaw opening, but its
      stress is far less than the one under the tight biting status. Perhaps the TMJ
      symptom induced under the large jaw opening status is mainly caused by the
      displacement of the articular disc. Under the large jaw opening status, the
      condylar cartilage plays a vital role in dispersing the stress. This method can
      be applied for carrying out individualized mechanical analysis on the patients
      with TMD.

PMID- 26309559
TI  - TP53 codon 72 polymorphism and susceptibility to cervical cancer in the Chinese
      population: an update meta-analysis.
AB  - BACKGROUND: Although many epidemiologic studies investigated the TP53 codon 72
      polymorphism and its association with cervical cancer (CC), definite conclusions
      cannot be drawn. AIM OF THE STUDY: To evaluate the association between TP53 codon
      72 polymorphism and risk of cervical cancer in the Chinese population. METHODS: A
      computerized literature search was carried out in PubMed, Springer Link, Ovid,
      Chinese Biomedical Database (CBM), Chinese National Knowledge Infrastructure
      (CNKI), and Chinese Wanfang Database to collect relevant articles. Odds ratios
      (ORs) with 95% confidence intervals (CIs) were used to calculate the strength of
      association. RESULTS: A total of 16 studies including 1684 CC cases and 1178
      controls were involved in this meta-analysis. Overall, significant increased
      association was found between the Pro/Pro carriers and CC risk when all studies
      in Chinese population pooled into the meta-analysis (heterozygous model: OR =
      1.22, 95% CI: 1.01-1.46). In subgroup analyses stratified by ethnicity and source
      of controls, the same results were observed in Han and in hospital-based studies.
      CONCLUSION: Our results suggest that the TP53 codon 72 polymorphism may be
      potential biomarkers for CC risk in the Chinese population, especially for Han
      Chinese, and studies with wider spectrum of population are required for definite
      conclusions.

PMID- 26309560
TI  - Mutational analysis of CHRNB2, CHRNA2 and CHRNA4 genes in Chinese population with
      autosomal dominant nocturnal frontal lobe epilepsy.
AB  - OBJECTIVE: The present study aims to investigate the gene mutations of CHRNB2,
      CHRNA2 and CHRNA4 in Chinese population with autosomal dominant nocturnal frontal
      lobe epilepsy (ADNFLE). METHODS: 257 ADNFLE patients (74 sporadic and 32
      familial) were collected, including 42 pedigree patients and 215 sporadic cases.
      Exon mutational screening of CHRNB2, CHRNA2 and CHRNA4 was performed by direct
      PCR sequencing. RESULTS: No published mutations of CHRNB2, CHRNA4 and CHRNA2
      genes were detected in this study. Three kinds of c.SNP (c.66C> T, c.249C> T,
      c.375A> G) were detected on the 2(nd) and 5(th) exons of CHRNA2; six kinds of
      c.SNP (c.639T> C, c.678T> C, c.1209G> T, c.1227T> C, c.1659G> A, c.1629C> T) were
      detected on the 5(th) exon of CHRNA4. Three novel mutations were discovered,
      respectively locating on the exon 5 of CHRNA4 gene (c.570C> T), 5(th) and 6(th)
      exons of CHRNB2 gene (c.483C> T and c.1407C> G). The three mutations were absent
      in 200 healthy controls, indicating that the mutations were very rare.
      CONCLUSION: CHRNA4, CHRNB2 and CHRNA2 may be not the causative genes of Chinese
      ADNFLE population. Whether the three novel synonymous mutations were genetic
      factors of ADNFLE pathogenesis in Chinese Han population needs to be further
      studied.

PMID- 26309561
TI  - Studies on Budd-chiari syndrome complicated with hepatocellular carcinoma: most
      patients without inferior vena cava obstruction.
AB  - BACKGROUND: To investigate the characteristics of Budd-Chiari syndrome (B-CS)
      types, rate of HCC complicated by different types of B-CS and values of CTA in
      diagnosis of B-CS and HCC complicated by B-CS. MATERIAL AND METHODS: 494 patients
      with B-CS were analyzed retrospectively. All patients underwent CTA, which was
      used to assess the accuracy of diagnosing B-CS and the rate of HCC complicated by
      various kinds of B-CS. Digital subtraction angiography (DSA) and pathological
      examination were used as gold standard. RESULTS: Among 494 patients diagnosed by
      DSA, there were 21 (4.3%) cases of inferior vena cava type, 80 (16.2%) cases of
      hepatic vein type and 393 (79.6%) cases of hepatic vein combined with inferior
      vena cava complex type. The accuracy of diagnosing B-CS by CTA was 86.6%
      (428/494), in which the accuracy of diagnosing inferior vena cava type was 85.7%
      (18/21), 83.8% (67/80) for hepatic vein type and 87.3% (343/393) for complex
      type. The rate of HCC complicated by B-CS was 12.8% (63/494), among which
      inferior vena cava type was 4.8% (1/21), hepatic vein type was 11.3% (9/80) and
      complex type was 13.5% (53/393). There were no statistic differences between
      these three types (P=0.459). The accuracy of diagnosing HCC by CTA was 82.5%
      (52/63). CONCLUSION: B-CS in patients from China's Yellow River basin is mainly
      hepatic vein combined with inferior vena cava complex type, which is more likely
      to be complicated by HCC. CTA plays an important role in diagnosing B-CS and HCC
      complicated by B-CS.

PMID- 26309562
TI  - Diabetes mellitus and risk of deep vein thrombosis after total knee replacement:
      a meta-analysis of cohort studies.
AB  - The impact of pre-existing diabetes on the development of deep vein thrombosis
      (DVT) remains unclear. We performed a meta-analysis of cohort studies to evaluate
      the risk of DVT in patients with and without pre-existing diabetes. We searched
      Pubmed, Embase, and Cochrane databases from the inception to December 2014 for
      cohort studies assessing the effect of diabetes on the incidence of DVT. Pooled
      odds ratio (OR) with 95% confidence interval (CI) was calculated using random- or
      fixed-effect models. Six cohort studies were included in this meta-analysis. A
      fixed-effects model meta-analysis showed that pre-existing diabetes was
      associated with an increased risk of DVT (OR 1.36; 95% CI 1.07-1.72; P=0.01),
      with moderate heterogeneity among the studies (I(2) =46.2; P=0.10). When patients
      were divided into two subgroups based on the method of screening DVT, there was
      no significant heterogeneity in each subgroup. Our meta-analysis suggested that
      pre-existing diabetes was associated with an increased risk of DVT after total
      knee replacement. However, the result should be interpreted with caution because
      of the potential bias and confounding in the included studies. 

PMID- 26309563
TI  - Lack of association between bcl-2 expression and prognosis of osteosarcoma: a
      meta-analysis.
AB  - Several studies investigated the bcl-2 in prognosis of osteosarcoma, but no
      consistent conclusions were achieved. This meta-analysis was conducted to
      determine the prognostic role of bcl-2 in osteosarcoma. Databases including
      Pubmed, Embase, Cochrane library, Google scholar, Wanfang and CNKI were searched
      systematically up to March 1, 2014. Cohort studies assessing the prognostic role
      of bcl-2 expression in patients with osteosarcoma were included. Pooled odds
      ratio (OR) with 95% confidence intervals (95% CI) was adopted. Sensitivity
      analysis was also performed. Five studies with a total of 202 patients were
      included in final analysis. Compared with positive bcl-2 expression, negative bcl
      2 expression was associated with better 3-year overall survival (OR=0.21, 95% CI
      0.07-0.65, P=0.007). No significant difference was achieved with respect to 5
      year overall survival (OR=0.76, 95% CI 0.42-1.38, P=0.264) and diseases-free
      survival (OR=1.20, 95% CI 0.47-3.06, P=0.709). Sensitivity analysis indicates the
      conclusion was stable. This meta-analysis suggests that the bcl-2 expression may
      be independent with the prognosis for patients with osteosarcoma. Nevertheless,
      additional well-designed studies with larger sample size are needed to further
      confirm the results. 

PMID- 26309564
TI  - A new source of structural autograft for ACDF surgery: cervical laminae.
AB  - STUDY DESIGN: A prospective study and a technical note. BACKGROUND: Autograft is
      considered to be the gold standard in achieving optimal fusion in anterior
      cervical discectomy and fusion (ACDF). In patients with combined postero-anterior
      cervical procedure, whether the cervical laminae harvested from laminectomy can
      be used as astructural bone graft in ACDF? Few studies have reported about this.
      OBJECTIVE: To describe the clinical and radio graphic outcomes in patients
      undergoing combined postero-anterior cervical surgery using autologous laminae as
      bone graft in ACDF. METHODS: Twenty-two patients (13 males, 9 females) with
      cervical spondylotic myelopathy underwent one-level combined postero-anterior
      procedure with anterior plate fixation from January 2010 to January 2014. All the
      patients received computed tomography scan before surgery and the heights of the
      target laminae and the middle intervertebral space were measured. Then, patients
      underwent combined postero-anterior surgery with laminectomy and ACDF. The
      structural laminae obtained from laminectomy were used as bone graft in ACDF. The
      clinical and radiographic outcomes of the patients were analyzed and the
      effectiveness and safety of the surgery was evaluated. RESULTS: The average
      heights of the target laminae and the middle intervertebral space were 11.18+/
      1.05 mm and 5.75+/-0.58 mm, respectively. Statistical significant difference was
      found between the heights of the laminae and the space (P<0.001). The mean
      operative time was 192+/-37 minutes with an average blood loss volume of 235+/-71
      ml. All patients were followed up and the average follow-up period was 17.5+/-3.1
      months. All patients had immediate postoperative resolution of symptoms and
      radiographic evidence of solid fusion 3 months later. Postoperatively, excellent
      results were reported in 62.5%, good results in 18.8%, and fair results in 18.8%
      of the patients according to Odom's criteria. Visual analog scale score of the
      neck and extremities pain was significantly decreased after the surgery
      (P=0.014). The average preoperative and postoperative lordosis angles of the
      cervical spine were24.42 degrees +/-13.84 degrees  and 32.91 degrees +/-7.79
      degrees , and the difference was significant (P<0.01). Little loss of the angle
      was noted at final follow-up (32.91 degrees +/-7.79 degrees  VS 29.30+/-7.88,
      P=0.51). Anterior intervertebral space height was significantly increased
      (P<0.001) after the surgery and a little declined at final follow-up (P=0.43). No
      intraoperative complication was noted in the patients and three patients got self
      limiting dysphagia postoperatively, who recovered spontaneously. CONCLUSION: In
      patients undergoing combined postero-anterior cervical surgery, structural
      autograft harvested from the laminae provides an alternative to anterior iliac
      crest grafting.

PMID- 26309565
TI  - miR-206 inhibits non small cell lung cancer cell proliferation and invasion by
      targeting SOX9.
AB  - BACKGROUND: MicroRNAs (miRNAs) are a class of small non-coding RNAs that have
      been suggested to play an essential role in tumorigenesis. miR-206 functions as a
      tumor suppressor in several cancers. However, its role in non small cell lung
      cancer (NSCLC) remains unclear. METHODS: Expression levels of miR-206 in NSCLC
      tissues and cell lines were determined by quantitative real-time PCR (qRT-PCR).
      Then, we investigated the role of miR-206 on NSCLC cell proliferation, migration
      and invasion. Furthermore, luciferase reporter assay was performed to confirm the
      target gene of miR-206 and the results were validated in NSCLC cells. RESULTS: In
      the present study, our results showed that miR-206 was decreased in NSCLC tissues
      compared with adjacent non-tumor tissues. Forced overexpression of miR-206
      significantly inhibited cell proliferation, migration and invasion of NSCLC
      cells. SOX9 was found to be a target of miR-206. Furthermore, down-regulation of
      SOX9 by shRNA performed similar effects with overexpression of miR-206.
      CONCLUSIONS: Our study suggested that miR-206 acts as tumor suppressor in NSCLC
      partially via targeting SOX9.

PMID- 26309566
TI  - Role of IL-6 in the invasiveness and prognosis of glioma.
AB  - IL-6 is a cytokine secreted by glioma cells and plays an important role in the
      tumor growth. However, the impact of IL-6 on the invasiveness and prognosis of
      glioma is still unclear. In this study, immunohistochemistry was performed to
      determine the expression of IL-6 in 86 glioma tissues, and ELISA to measure IL-6
      in the serum and cerebrospinal fluid (CSF) of these patients. Results showed, as
      ccompared with normal controls, the IL-6 in the glioma, CSF and serumincreased
      remarkably, and increased with the elevation of glioma grade. In addition, IL-6
      in the supernatant was also detectable in glioma cell lines U251, U87, A172 and
      T98G. Transwell invasion assay showed that the invasiveness of glioma U87 cells
      and U251 cells increased remarkably after exogenous IL-6 treatment. Survival
      analysis indicated higher IL-6 before surgery and significantly reduction in IL-6
      after operation in the serum and CSF predicted a poor prognosis. Thus, we
      speculate that, the poor prognosis of glioma is related to the IL-6 autocrine in
      the glioma and the IL-6 induced tumor growth and invasion. IL-6 may serve as a
      therapeutic target for glioma patients and IL-6 in the CSF and serum of glioma
      may be used to predict the prognosis of these patients. 

PMID- 26309567
TI  - Expression of miRNA-1233 in placenta from patients with hypertensive disorder
      complicating pregnancy and its role in disease pathogenesis.
AB  - OBJECTIVE: This study is to investigate the expression of miRNA-1233 in placental
      tissue from patients with hypertensive disorder complicating pregnancy (HDCP) and
      its role in disease pathogenesis. METHODS: The expression levels of miRNA-1233
      and HoxB3 in placental tissue from HDCP patients and normal control subjects, as
      well as in the in vitro trophoblast cells, were detected with real-time PCR and
      Western blot analysis. The proliferation and invasion abilities of trophoblast
      cells were assessed by the cell counting kit (CCK)-8 and transwell chamber
      assays, respectively. Dual-luciferase reporter assay was performed to evaluate
      the interaction between miRNA-1233 and Hoxb3. RESULTS: Real-time PCR showed that,
      compared with the control group, the expression levels of miRNA-1233 were
      significantly elevated in placental tissue from HDCP patients. On the other hand,
      both the mRNA and protein expression levels of HoxB3 were significantly decreased
      in the HDCP group. Moreover, the mRNA and protein expression levels of HoxB3 were
      significantly declined by the transfection of miRNA-1233 mimics in trophoblast
      cells. Bioinformatics analysis and the dual-luciferase reporter gene assay showed
      that, miRNA-1233 targeted HoxB3 in the 3'-UTR and suppressed the gene expression.
      In addition, the results from the CCK-8 and transwell chamber assays showed that,
      the transfection of miRNA-1233 significantly decreased the proliferation and
      invasion abilities of the trophoblast cells. CONCLUSION: In placental tissue from
      HDCP patients, up-regulated miR-1233 could suppress the expression of HoxB3, and
      then inhibit the invasion of trophoblast cells, which might contribute to the
      disease pathogenesis.

PMID- 26309568
TI  - Cone-beam computed tomography study of prevalence and location of MB2 canal in
      the mesiobuccal root of the maxillary second molar.
AB  - The maxillary second molar (2 MM) has the most complex root canal system, and a
      high percentage of treatment failures is due to the impossibility of locating,
      instrumenting and obturating the second mesiobuccal canal (MB2). The aim of this
      study was to describe in vivo the prevalence and location of the MB2 canal in the
      mesiobuccal root of the permanent maxillary second molar through CBCT image
      analysis. Two hundred twenty five CBCT images of 2 MM were studied. In the
      presence of the MB2 canal, the floor of the coronal cavity was located and
      advanced every 1 mm apically to standardize observation. The geometric location
      in relation to the primary mesiobuccal (MB1) and palatal (P) canals was done by
      locating the central points of the canal and projecting a line between them,
      together with a perpendicular line between MB1-P (point T). The data were
      analyzed using descriptive statistics, with a value of P < 0.05 being
      statistically significant. The MB2 canal was identified in 48% of the cases. It
      was located 2.2 +/- 0.54 mm palatally and 0.98 +/- 0.35 mesially to the MB1
      canal. The average age of the subjects where it was found was 26.36 +/- 10.85
      years. Its location was more frequent in men (63%), and no differences were
      observed in its appearance in the hemi-arch. It is necessary to know the high
      probability of finding the MB2 canal in the maxillary second molar, and the CBCT
      is a good diagnostic tool for its detection and exploration. 

PMID- 26309569
TI  - Association between MTHFR A1298C polymorphism and hepatocellular carcinoma risk.
AB  - BACKGROUND: Hepatocarcinogenesis is a complex process that is influenced by many
      factors. Several studies have investigated the relationship between MTHFR A1298C
      polymorphism and hepatocellular carcinoma (HCC) risk, but the results are
      inconsistent. Therefore, we performed a meta-analysis covering a large sample
      size to address this controversy. METHODS: Eligible studies were searched using
      PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI) databases. A
      total of 7 studies from 6 publications with 2035 cases and 3096 controls were
      included. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) was
      calculated by the fixed or random effects to evaluate the correlation between
      MTHFR A1298C polymorphism and HCC risk. The Q statistic and I(2) statistic were
      used to assess the statistical heterogeneity among studies. Publication bias was
      evaluated by Egger's linear regression test and Begg's funnel plot. RESULTS: In
      present study, the results showed that MTHFR A1298C polymorphism was not
      significantly associated with risk of HCC based on CC + AC vs. AA genetic model
      (OR=1.01, 95% CI=0.90-1.13). Similarly, in the subgroup analysis by ethnicity, no
      significant HCC risk was found in Asian population (OR=1.02, 95% CI=0.91-1.14).
      In the subgroup analysis based on source of control, we found that MTHFR A1298C
      polymorphism showed no effects on the occurrence of HCC in the population-based
      (PB) and hospital-based (HB) group (OR=0.97, 95% CI=0.83-1.15; OR=1.04, 95%
      CI=0.89-1.21). CONCLUSION: This meta-analysis suggested that MTHFR A1298C
      polymorphism may not be a risk factor for HCC.

PMID- 26309570
TI  - Upregulation of miR-195 enhances the radiosensitivity of breast cancer cells
      through the inhibition of BCL-2.
AB  - AIMS: To investigate the effect of miR-195 overexpression on radiosensitivity and
      the relevant molecular mechanisms in breast cancer. METHODS: miR-195 mimics were
      transfected to breast cancer cell line MCF-7 by gene transfection; miR-195
      expression level in cells was determined by real-time quantitative PCR. Cellular
      viability was observed by colony formation assay after the cells were irradiated
      with X-ray. Apoptosis was detected by annexin V/propidium iodide (PI) staining.
      Protein expression was evaluated by Western blot assay. RESULTS: After miR-195
      mimics were transfected, miR-195 expression in breast cancer cells was
      significantly upregulated (P < 0.05). miR-195 overexpression significantly
      enhanced the response to radiation of MCF-7 cells with a decrease in colony
      survival at individual doses of X-ray (P < 0.05). After the cells were irradiated
      with 5 Gy, apoptotic rate was significantly increased in miR-195-overexpressed
      group with a rate of 18.13% +/- 1.57%; moreover, BCL-2 protein expression was
      significantly downregulated (P < 0.05). CONCLUSION: Exogenetic miR-195 expression
      could significantly enhance the radiosensitivity of human breast cancer cells;
      this finding may be attributed to BCL-2 downregulation to promote radiation
      induced apoptosis.

PMID- 26309571
TI  - Activation of spinal NF-KB mediates pain behavior induced by plantar incision.
AB  - A growing body of evidence indicates that the activation of nuclear factor kappa
      B (NF-kappaB) pathway was involved in neuropathic and inflammatory pain, however,
      the role of NF-kappaB in incisional pain is still unclear. Therefore, in this
      study, we investigated whether the activation of NF-kappaB in the spinal cord is
      involved in pain hypersensitivity after a plantar incision in the rat hind paw.
      After rats received a plantar incision surgery, mechanical allodynia and thermal
      hyperalgesia were determined by von Frey filaments and radiant heat,
      respectively. Western blot was used to determineNF-kappaB activation at different
      time points after incision. The NF-kappaB inhibitor pyrrolidinedithiocarbamate
      (PDTC) was administered intrathecally 30 min before hind paw plantar incision to
      determine the role of NF-kappaB in incision-induced pain. Our results showed that
      the expression level of NF-kappaB was significantly increased in spinal cord
      dorsal horn from 30 min to 3 days after the incision. Intrathecal pretreatment of
      PDTC attenuated incision-induced mechanical allodynia and thermal hyperalgesia.
      Furthermore, PDTC significantly reduced the expression level of c-Fos in the
      dorsal horn after plantar incision. Taken together, plantar incision-induced pain
      behaviors can be prevented by the NF-kappaB inhibitor. Our results suggest that
      the blockage of the NF-KB signaling pathway might represent a valuable
      alternative for treating postoperative pain. 

PMID- 26309572
TI  - Construction and identification of Complex DNA vaccine of hepatitis B and
      Toxoplasma gondii.
AB  - OBJECTIVE: To construct and identify multi-gene recombinant expression vector
      pcDNA3-HBsAg-p30-ROP2. METHOD: Primers were designed according to the gene
      sequences of restriction enzyme cutting site of recombinant pcDNA3-p30-ROP2 and
      hepatitis B surface antigen (HBsAg). The target fragment of HBsAg was amplified
      and cloned to expression vector pcDNA3-p30-ROP2 by restriction enzyme digestion
      and ligation. The recombinant expression vector pcDNA3-HBsAg-p30-ROP2 was
      identified by PCR detection, followed by enzyme restriction and sequencing.
      RESULTS: The target fragment of HBsAg was successfully amplified, and the multi
      gene eukaryotic expression vector pcDNA3-HBsAg-p30-ROP2 was established. PCR
      detection and restriction enzyme digestion showed that the length of the target
      fragment was consistent with the theoretical value. The recombinant expression
      vector contained the complete sequences of p30-ROP2 compound gene and HBsAg.
      CONCLUSION: Multi-gene recombinant expression vector pcDNA3-HBsAg-p30-ROP2 was
      successfully established. The constructed expression vector could be used to
      develop multi-gene nucleic acid vaccines.

PMID- 26309573
TI  - Lack of association of CYP11B2-344C/T polymorphism with essential hypertension: a
      meta-analysis.
AB  - OBJECTIVE: A meta-analysis was carried out to evaluate the correlation between
      CYP11B2-344C/T polymorphism and essential hypertension susceptibility. METHODS:
      By retrieving relevant databases and collecting domestic and international
      literatures about the correlation between CYP11B2-344C/T polymorphism and
      essential hypertension, the quality of literature were evaluated according to
      NEWCASTLE-OTTAWA case-control study quality rating scale (NOS). RevMan 5.0 was
      used to select the best genetic model, analysis the heterogeneity, calculate
      combined OR and the 95% CI. RESULTS: 8532 subjects were included in this study.
      Compared with the control group, the OR (95% CI) values of dominant model,
      recessive model, and additive model were 1.01 (95% CI: 0.81~1.25), 1.03 (95% CI:
      0.83~1.19) and 1.10 (95% CI: 0.93-1.29). CONCLUSION: There is no evidence to
      confirm that CYP11B2 (-344C/T) polymorphism is associated with susceptibility of
      essential hypertension.

PMID- 26309574
TI  - The association between serum miR-155 and natural killer cells from tuberculosis
      patients.
AB  - Tuberculosis (TB) is still an infectious disease that greatly threatens human
      health, and is always refractory to the current therapeutic modalities.
      Accumulated evidence revealed that microRNAs (miRNAs) are closely with various
      pathologies, such as TB. The possibilities of miRNAs as diagnostic biomarkers and
      therapeutic targets have been proved. However, it is still unknown if miRNA is
      implicated in the TB-associated immunity. This study revealed that miR-155, which
      has been shown to suppress the activation of natural killer (NK) cells associated
      with tumors, was downregulated in serum samples of TB patients (n=90), compared
      with healthy controls (n=31). Cytotoxicity assays indicated that NK cells, which
      have been demonstrated to promote TB progression, exhibited lower cytotoxicity in
      high serum miR-155 TB patients (n=37). There is an inverse relationship between
      serum miR-155 abundance and NK cell cytotoxicity (R=-0.659, P=0.000). Further
      studies demonstrated that miR-155 level is inversely associated with the
      concentration of TNFalpha secreted by NK cells from TB patients (n=37, R=-0.694,
      P=0.000). Collectively, serum miR-155 level was shown to be negatively associated
      with the TB-suppressing activity of NK cells, and this miRNA can be used as a
      potential therapeutic agent for TB treatment. 

PMID- 26309575
TI  - Laparoscopic total colectomy and proctocolectomy for the treatment of familial
      adenomatous polyposis.
AB  - OBJECTIVE: To evaluate the safety, feasibility and efficacy of Laparoscopic
      prophylactic treatment of familial adenomatous polyposis (FAP). METHODS:
      Perioperative data and surgical outcomes of 11 FAP patients who underwent
      laparoscopic surgery between January 2012 and June 2014 in our hospital were
      analyzed retrospectively. Results 2: Patients had laparoscopic total
      proctocolectomy with ileostomy, and 9 patients had laparoscopic total colectomy
      with ileorectal anastomosis. The median number of harvested lymph nodes was 36
      (range, 21~46). The mean operating time was 330 minutes with a range of 240 to
      380 minutes. Blood loss ranged from 90 to 200 ml with a median being 150 ml. The
      median incision length was 4 (3-5) cm. The bowel function recovered by the third
      (range from 2~4 day) postoperatively. The follow-up time of these patients were
      3~32 months (median 20 months) respectively and no local recurrence or distant
      metastases were found. CONCLUSION: Laparoscopic prophylactic treatment for FAP
      can be performed safely and effectively with the advantage of minimal invasion by
      experienced surgeons.

PMID- 26309576
TI  - NAT1 polymorphisms and cancer risk: a systematic review and meta-analysis.
AB  - PURPOSE: To investigate the association between the N-acetyltransferase 1 (NAT1)
      slow and rapid acetylation phenotypes with cancer risk based on a meta-analysis.
      METHODS: Previously published case-control studies were retrieved from PubMed,
      Embase, and Web of Science. Odds ratios (ORs) with 95% confidence intervals (CIs)
      were determined to assess the relationship between NAT1 polymorphisms and cancer
      risk. RESULTS: A total of 73 studies (24874 cases and 30226 controls) were
      included in this meta-analysis. No significant association was identified between
      NAT1 polymorphisms (slow acetylation versus rapid acetylation genotypes: OR =
      0.978, 95% CI = 0.927-1.030, P < 0.001 for heterogeneity, I(2) = 45.5%) and
      cancer risk, whereas a significantly reduced risk of pancreatic cancer was
      identified in individuals with NAT1 slow acetylation genotype (OR = 0.856, 95% CI
      = 0.733-0.999, P =0.509 for heterogeneity, I(2) = 0). When the NAT1 slow
      acetylation genotype was analysed on the basis of stratified analyses of
      ethnicity, a significantly reduced risk of head and neck cancers was found among
      Asian (OR=0.281, 95% CI = 0.127-0.622). When the NAT1 slow acetylation genotype
      was analysed on the basis of stratified analyses of source of control, only
      significantly reduced risks of colorectal cancer (OR = 0.882, 95% CI = 0.798-
      0.974, P = 0.212 for heterogeneity, I(2) = 22.9) and pancreatic cancer (OR=0.856,
      95% CI = 0.733-0.999, P = 0.509 for heterogeneity, I(2) = 0) were found among
      hospital-based studies. CONCLUSIONS: No significant association between the NAT1
      polymorphisms and the risk of cancer was found except for pancreatic cancer.

PMID- 26309577
TI  - Mitochondrial and cytoskeletal alterations are involved in the pathogenesis of
      hydronephrosis in ICR/Mlac-hydro mice.
AB  - The pathogenesis of congenital hydronephrosis in laboratory animals has been
      studied for many years, yet little is known about the underlying mechanism of
      this disease. In this study, we investigated a MS-based comparative proteomics
      approach to characterize the differently expressed proteins between kidney tissue
      samples of ICR/Mlac-hydro and wild-type mice. Interestingly, proteomic results
      exhibited several mitochondrial protein alterations especially the up-regulation
      of 60 kDa heat shock protein (Hsp60), stress-70 protein (GRP75) dysfunction, and
      down-regulation of voltage-dependent anion-selective channel protein 1 (VDAC-1).
      The results demonstrated that mitochondrial alteration may lead to inadequate
      energy-supply to maintain normal water reabsorption from the renal tubule,
      causing hydronephrosis. Moreover, the alteration of cytoskeleton proteins in the
      renal tubule, in particular the up-regulation of tubulin beta-4B chain (Tb4B) and
      N-myc downstream-regulated gene 1 protein (Ndr-1) may also be related due to
      their fundamental roles in maintaining cell morphology and tissue stability. In
      addition, cytoskeletal alterations may consequence to the reduction of
      glyceraldehydes-3-phosphate dehydrogenase (GAPDH), cytoplasmic enzyme, which
      modulates the capacity of structural proteins. Our findings highlight a number of
      target proteins that may play a crucial role in congenital hydronephrosis and
      emphasize that the disorder of mitochondria and cytoskeleton proteins may be
      involved. 

PMID- 26309578
TI  - Radix Bupleuri ameliorates depression by increasing nerve growth factor and brain
      derived neurotrophic factor.
AB  - BACKGROUND: Chinese herb Radix Bupleuri has been regarded effective to improve
      treatment of depression, but the molecular mechanism remains unknown. Low levels
      of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF)
      increase the likelihood of developing the depression. Therefore, we want to know
      whether Radix Bupleuri affects the levels of these factors. METHODS: A total 160
      hemodialysis patients were diagnosed with depression and randomly assigned to two
      groups: Radix Bupleuri group (received 1 g root power of Radix Bupleuri in a
      capsule daily Radix Bupleuri) and control group (receive placebo). RESULTS: After
      three-month follow-up, the patients who received Radix Bupleuri had greater
      improvement in depression symptoms, anxiety symptoms and general functioning via
      controls after three-month follow-up (P < 0.05). Serum NGF levels were
      significantly higher in subjects accepted Radix Bupleuris (178.64 +/- 52.18
      pg/mL) when compared to a control (103.54 +/- 31.23 pg/ml) (P < 0.01). Similarly,
      serum BDNF levels were significantly higher in subjects accepted Radix Bupleuris
      (1635.26 +/- 121.66 pg/ml) when compared to a control (516.38 +/- 44.89 pg/ml) (P
      < 0.01). The serum levels of NGF and BDNF were negatively related with Montgomery
      Asberg Depression Rating Scale (MADRS) and positively related with scores of RAND
      36 item Health Survey (RAND-36) (P < 0.01). CONCLUSION: Thus, Radix Bupleuri
      ameliorates the patients with depression by increasing serum levels of NGF and
      BDNF. Radix Bupleuri should be developed a new drug for the therapy of
      depression.

PMID- 26309579
TI  - The prevalence and adverse profiles of fatty liver disease among different ethnic
      public servants in Urumqi of Xinjiang Uygur Autonomous Region in China.
AB  - BACKGROUND: The purpose of this survey was to confirm the prevalence and adverse
      profiles of fatty liver disease among different ethnic public servants in Urumqi
      of Xinjiang. METHODS: The cross-sectional study were implemented among serving
      and retired public servants who participated in the annual physical check-up
      including abdominal ultrasonography from April 2012 to April 2013 at the health
      promotion center of the First Affiliated Hospital of Xinjiang Medical University
      in Urumqi. The information including questionnaires, anthropometric indexes and
      biochemical profiles were collected to analyze. RESULTS: There were 46612
      individuals ranging from 20 to 93 years of age included in the analysis. There
      were 39120 of Han, 4148 of Uygur, 877 of Kazakh, 2098 of Hui, and 369 of other
      ethnic groups. The prevalence of FLD in total, Han, Hui, Uygur, Kazakh and other
      ethnic group were 32.0%, 31.2%, 31.5%, 39.3%, 36.4% and 32.8%. Uygur was
      significantly higher than the other ethnic groups both male and female (P < 0.01)
      and male was higher than female regardless of ethnicity (P < 0.01). FLD co
      exiting with DM, hypertension, obesity, overweight and dysliplidemia (especially
      for hypertriglyceridemia) were common and distribution of these diseases were
      significantly different among various ethnicity (P < 0.01). Multiple logistic
      regression analysis indicated that there were different in adverse factors
      including age, gender, DM, obesity, dyslipidemia and hypertension of FLD among
      ethnicity and obesity having higher OR value in each ethnic group can be as
      predictive index of FLD. CONCLUSIONS: The high prevalence of FLD is present among
      public servants in Urumqi of Xinjiang, China. The prevalence of FLD is
      significantly different in different ethnic groups and genders. Distributions of
      adverse factors are disparate in different ethnicity. Comprehensive strategies
      for the prevention and treatment of FLD should be explored basing on the ethnic
      differences.

PMID- 26309580
TI  - Expression of bone morphogenetic protein 2 in rabbit radial defect site with
      different lengths.
AB  - BACKGROUND: It has been studied that the distribution of bone morphogenetic
      protein 2 is regular under bone defect situation. OBJECTIVE: To observe the
      expression of bone morphogenetic protein 2 in rabbit radial defect site with
      different lengths. METHODS: Forty-eight New Zealand rabbits were divided into two
      groups randomly. 0.5 cm bone defect and 3.0 cm bone defect were made by wire saw
      at the middle part of radius bone after anaesthesia. RESULTS AND CONCLUSIONS:
      Western blot results showed that in the 0.5 cm bone defect group, the expression
      of bone morphogenetic protein 2 of the tissues in the bone defect site was
      increased gradually at 1, 3, 4 weeks after operation, and the expression in each
      defect group was increased when compared with that immediately after injury
      (P<0.05). In the 3.0 cm bone defect group, the expression of bone morphogenetic
      protein 2 of tissues in bone defect site was increased gradually and reached to
      its peak at 3 weeks after the operation (P<0.05). The peak value in the 3.0 cm
      bone defect group was significantly higher than that in 0.5 cm bone defect group
      (P<0.05). The peak value was maintained in high level. The comparison of bone
      callus formation showed that the bone callus formation of 3.0 cm bone defect
      group was less than that of the 0.5 cm bone defect group at 3 and 4 weeks after
      operation (P<0.05). The results indicate that expression of the bone
      morphogenetic protein 2 in 3.0 cm bone defect site is increased significantly,
      but the expression level cannot make the bone defect heal itself.

PMID- 26309581
TI  - Over-expression of TWIST, an epithelial-mesenchymal transition inducer, predicts
      poor survival in patients with oral carcinoma.
AB  - TWIST, an epithelial-mesenchymal transition inducer, has been thought to play a
      critical role in the progression of a number of malignancies. Published studies
      reporting the association of TWIST expression with oral carcinoma risk has
      yielded conflicting results. Thus, we conducted a meta-analysis to address this
      controversy. After rigorous searching and screening, a total of seven studies
      were included. The results showed that the TWIST positive expression rate in oral
      cancer tissues was higher than that in the normal tissues. TWIST expression might
      have a correlation with clinical features such as low differentiation, advanced
      clinical stage, presence of lymph node metastasis and local recurrence, but not
      age, gender, T stage and smoking and drinking. The data suggested that TWIST
      might play critical roles in the cancer progression and act as a prognostic
      factor in oral cancer patients. 

PMID- 26309582
TI  - Detection of 19 types of para-arachidonic acids in five types of plasma/serum by
      ultra performance liquid chromatography-tandem mass spectrometry.
AB  - The aim of this study was to examine the consistency of ultra performance liquid
      chromatography-tandem mass spectrometry (UPLC-TMS) in detecting the levels of
      para-arachidonic acids (PAAs) among differently processed plasma/serum samples.
      Ethylenediaminetetraacetic acid (EDTA)-K2, sodium citrate, heparin lithium,
      coagulant/separation gel, and coagulant-free vacuum blood-sampling tubes were
      used to collect the fasting blood samples from 15 volunteers. All blood samples
      were subjected to solid-phase extraction using an Oasis HLB MUElution 96-well
      plate, and UPLC-TMS was used to detect 19 types of PAAs in the blood samples.
      Within the plasma samples, the concentrations of 5, 6-DHET; 11, 12
      epoxyeicosatrienoic acid (EET); 5-hydroxyeicosatetraenoic acid (HETE);
      leukotriene B4 (LTB4); plasma thromboxane B2 (TXB2); and 12-HETE were
      significantly higher in the heparin lithium group than in the EDTA-K2 and sodium
      citrate groups. Within the serum samples, the concentration of LTB4 was
      significantly higher in the coagulant/separation gel group than in the coagulant
      free group, while that of TXB2 was significantly higher in the coagulant-free
      group than in the coagulant/separation gel group. The levels of some types of
      PAAs in differently processed plasma/serum samples were inconsistent, and the
      concentrations of 5, 6-DHET; 5-HETE; 12-HETE; TXB2; and LTB4 were significantly
      higher in the two serum samples and the heparin lithium group than in the EDTA-K2
      and sodium citrate groups. 

PMID- 26309583
TI  - Investigation of the current situation of massive blood transfusion in different
      surgical departments: a large multicenter study in China.
AB  - OBJECTIVE: This study aims to learn about the current situation of surgical
      massive blood transfusion of different surgical departments in China's Tertiary
      hospitals, which could provide the basis for the formulation of guidelines on
      massive blood transfusion. METHOD: A multicenter retrospective research on the
      application status of blood constituents during massive blood transfusion was
      conducted and a comparative analyses of survival and length of hospitalization in
      patients from different departments (trauma, cardiac surgery, obstetric
      conditions, or other common surgeries), were performed. RESULT: In China, during
      massive blood transfusion the ratio of the dosage of fresh frozen plasma to the
      dosage of red blood cell suspension reached 1:1-2, while the dosage of platelet
      and cryoprecipitate appeared to be very small. The risk of in-hospital death were
      associated with the primary disease in patients receiving massive blood
      transfusion (Log-Rank P = 0.000), cardiac surgery and trauma patients who
      received massive blood transfusion have a higher risk of death rate. CONCLUSIONS:
      Patients undergoing massive blood transfusion among different surgical
      departments have a certain difference in use of blood transfusion, mortality rate
      and the time of death. Our findings suggested that we should set up an
      independent transfusion program in cardiac surgery and trauma patients of massive
      blood transfusion.

PMID- 26309584
TI  - Both PON1 Q192R and CYP2C19*2 influence platelet response to clopidogrel and
      ischemic events in Chinese patients undergoing percutaneous coronary
      intervention.
AB  - Clopidogrel nonresponsiveness increases the recurrence of cardiovascular events
      in patients undergoing percutaneous coronary intervention (PCI). Previous studies
      found that genetic variants such as single nucleotide polymorphisms (SNPs) of
      CYP2C19 and PON1 may influence clopidogrel response, cause high platelet
      reactivity (HPR) and increase cardiovascular events. However, these studies were
      inconsistent and inconclusive, especially in the Eastern Asian population. In
      this study, we investigated the effects of genetic variants on clopidogrel
      response and clinical outcomes in Chinese patients undergoing PCI. A total of 336
      acute coronary syndrome patients undergoing PCI were included, 53 (15.77%) of
      whom were categorized as HPR. Among the 10 SNPs studied (ABCB1, CYP2C19*2,
      CYP2C19*3, CYP2C19*4, CYP2C19*17, CYP3A4, CYP3A5, ITGB3, P2Y12 and PON1 Q192R),
      the CYP2C19*4 and P2Y12 variants were not found in our population. The PON1 192Q
      and CYP2C19*2 alleles were significantly higher in the HPR group compared with
      the normal platelet reactivity (NPR) group (P=0.033 and 0.038, respectively),
      while the other SNPs were not significantly different between the two groups.
      Platelet aggregation of the PON1 192Q allele carriers was significantly higher
      than that of non-carriers both at baseline and 1 month after PCI (P=0.010 and
      0.024, respectively); this was the case for CYP2C19*2 allele carriers, as well
      (P=0.005 and 0.003, respectively). The risk of major adverse cardiovascular event
      (MACE) increased with the presence of the PON1 192Q and CYP2C19*2 alleles during
      6-month follow-up (P=0.012 and 0.003, respectively). In conclusion, both the PON1
      Q192R and CYP2C19*2 variants are associated with HPR and an increased risk of
      ischemic events in Chinese patients undergoing PCI. 

PMID- 26309585
TI  - Associations between Lectin-like, oxidized low-density lipoprotein receptor-1
      G501C and 3'-UTR-C188T polymorphisms with coronary artery disease: a meta
      analysis.
AB  - The background and purpose: Published data on the association between LOX-1 3'UTR
      C188T and G501C polymorphisms with coronary artery disease (CAD) risk are
      inconclusive. In order to derive a more precise estimation of the relationship, a
      meta-analysis was conducted. METHODS AND SUBJECTS: Crude ORs with 95% CIs were
      used to assess the strength of association between these polymorphisms and CAD
      risk. The pooled ORs were performed for homozygous model, heterozygous model,
      dominant model, and recessive model, respectively. RESULTS: A total of seventeen
      studies were involved in the meta-analysis with 5006 cases and 15053 controls for
      LOX-1 3'UTR C188T polymorphism and with 5905 cases and 15050 controls for G501C
      polymorphism. For LOX-1 3'UTR C188T polymorphism, significantly elevated CAD risk
      was associated with variant genotype when all studies were pooled into the meta
      analysis (TT vs. CC: OR = 1.35, 95% CI 1.08-1.69; dominant model: OR = 1.17, 95%
      CI 1.02-1.34; and recessive model: OR = 1.23, 95% CI 1.03-1.47). For LOX-1 G501C
      polymorphism, significantly increased CAD risk was also associated with variant
      genotype (GG vs. CC: OR = 1.42, 95% CI 1.07-1.87; CG vs. CC: OR = 1.28, 95% CI
      1.04-1.56; and dominant model: OR = 1.30, 95% CI 1.07-1.58). CONCLUSION: This
      meta-analysis suggests that the variant G allele of LOX1 3'UTR C188T and the
      variant C allele of G501C polymorphisms are low penetrant risk factors for
      developing CAD.

PMID- 26309586
TI  - Correlations of O3 therapeutic targets and imaging localization in lumbar
      intervertebral disc protrusion.
AB  - OBJECTIVE: This study aims to investigate correlations between the effects of O3
      target-injection treatment and imaging localization in lumbar intervertebral disc
      protrusion (LIDP). METHODS: 164 LIDP patients were divided into 3 groups: group
      A, the protrusion located at level I-III, region 1-2, domain a-b; group B, the
      protrusion located at level I-III, region 1-2, domain c-d; group C: the
      protrusion located at level I-III, region 3-4, domain a-b. The patients were
      treated with LIDP O3-target treatment + blocking therapy with epidural anti
      inflammatory analgesic liquid. RESULTS: Among the 164 LIDP patients, 95 patients
      (57.93%) exhibited the significant effectiveness after the treatment; 64 cases
      (39.02%) exhibited the effectiveness. The results of functional improvements
      revealed that 50 cases (53.76%) of sagittal plane and 54 cases of horizontal
      plane (55.67%) in the group A, 33 cases (35.48%) and 31 cases (31.96%) in the
      group C respectively were significantly better than those in the group B (10
      cases, 10.75%; 12 cases, 12.37%) (P < 0.05). The visual analogue scale (VAS)
      scores 1 week and 1 month after the treatment in the three groups were
      significantly decreased than those before the treatment (P < 0.05). The
      intergroup comparison revealed that the A group (1 week 2.28 +/- 0.85, 1 month
      1.21 +/- 0.27) and C (2.79 +/- 0.98, 1.38 +/- 0.55) were significantly better
      than the B group (3.92 +/- 1.14, 2.53 +/- 0.51) (P < 0.05). CONCLUSIONS: The O3
      target-injection treatment exhibited the best effects in treating the LIDP
      patients with the protrusion located at level I-III, region 1-2, domain a-b.

PMID- 26309587
TI  - Decreased plasma let-7c and miR-152 as noninvasive biomarker for non-small-cell
      lung cancer.
AB  - BACKGROUND: Non-small-cell lung cancer (NSCLC) is one of the leading causes of
      death. The aim of the present study was to compare the expression of let-7c and
      miR-152 in surgically resected NSCLC cases and healthy cases to evaluate their
      diagnostic impact. METHODS: This hospital-based case-control study included 120
      NSCLC patients and 360 healthy controls. The miRNA levels were measured via
      quantitative reverse transcription-polymerase chain reaction and their
      association with NSCLC was assessed by statistical data analysis and receiver
      operating characteristic curves. RESULTS: The expression of let-7c and miR-152 in
      plasma were found to be downregulated in the patients with NSCLC. Advanced
      studies showed that the plasma let-7c and miR-152 were correlated with the
      clinicopathological features such as histological classifications,
      differentiation status, lymph node metastasis and stage classifications. The ROC
      curves for the miRNAs revealed a strong diagnostic performance. ROC curve
      analyses revealed that both plasma let-7c and miR-152 could serve as valuable
      biomarkers for NSCLC cases from healthy controls with an AUC of 0.714 and 0.845.
      CONCLUSION: It was found that let-7c and miR-152 are significantly reduced in
      plasma samples of NSCLC patients. These findings suggest that detection of
      circulating let-7c and miR-152 can be developed into a noninvasive and rapid
      diagnostic tool for the individuals with NSCLC.

PMID- 26309588
TI  - Clinical-pathologic significance of CD163 positive macrophage in IgA nephropathy
      patients with crescents.
AB  - BACKGROUND: CD163, a marker of M2 macrophages, express anti-inflammatory
      properties. This study aims to investigate the difference of CD163 positive
      macrophages expression between IgA nephropathy patients with and without
      crescents. METHODS: Renal tissues from IgAN patients (n = 24), including IgAN
      with crescents (n = 10), IgAN without crescents (n = 14), minimal change disease
      (MCD, as disease control, n = 8) and normal control kidneys (negative control, n
      = 3), were included in this study. Expressions of CD163 and CD68 in renal tissues
      were detected by immunohistochemistry or immunofluorescence. RESULTS: Compared
      with IgAN without crescent, IgAN patients with crescents have lower serum albumin
      and poor renal function. CD163 was mainly expressed in acute tubulointerstitial
      lesions. CD163 positive cells accumulate in areas around tubules with RBC casts.
      CD163 positive cells can also be seen in tubular lumen. CD163 positive cells can
      be seen in glomerular lesions, including endocapillary hypercellularity, cellular
      crescent and fibrous-cellular crescent. There were more CD163 positive cells in
      tubulointerstitial and glomerular lesions in IgAN patients with crescents. CD163
      positive cells number in tubulointerstitial tissue was positive correlated with
      percentage of crescents, proteinuria, and negative correlated with serum albumin,
      eGFR. CD163 positive cells number in glomeruli was positive correlated with
      percentage of crescents, and was negative correlated with eGFR. Percentage of
      crescents was negative correlated with serum albumin, eGFR, and positive
      correlated with proteinuria. Dual staining showed that CD163 positive cells also
      expressed CD68. CONCLUSIONS: CD163 positive macrophages were involved in active
      crescent disease, acute tubular injury and glomerular lesions of IgAN with
      crescents.

PMID- 26309589
TI  - Physical fitness status of children and adolescents in Tianjin of China during
      past three decades: a cross-sectional study.
AB  - BACKGROUND: Significant changes in the society and lifestyle have been observed
      in China, which influences the physical fitness status of children and
      adolescents. This study aimed to estimate the physical fitness status in Tianjin
      during the past three decades. METHODS: Cross sectional survey was used in this
      study. The data were derived from the Chinese National Students' Physical Health
      Survey database (1985-2010) using stratified cluster randomized sampling method.
      A total of 58,006 subjects aged 7-21 were recruited. The ethics approval was
      obtained from the Ethics Committee of Tianjin Medical University before
      collecting data from the children and adolescents, and/or their parents/guardians
      on behalf of them. Also written informed consent was obtained before collecting
      data from the patients. The secular trend of the physical fitness status, Levels
      of height, weight, body mass index, and chest circumference in China were
      calculated. The increase velocity of according indexes were analyzed, gender and
      rural/urban difference were discussed afterwards. SPSS16.0 was used in the
      analysis. RESULTS: Levels of height, weight, body mass index, and chest
      circumference were obviously increased in 2010 compared to those levels in 1985,
      especially in the 9-13 age group. It was observed that the increase in the two
      crosses for height velocity between two genders of rural students was disappeared
      and the age of seven was important for the physical development. CONCLUSIONS: The
      circumstance was good for the physical development of the children and
      adolescents. The disappearance of the two crosses for height velocity between two
      genders of rural students in this study might be associated with factors such as
      nutritional status.

PMID- 26309590
TI  - The association between VEGF -634C/G polymorphisms and osteonecrosis of femoral
      head: a meta-analysis.
AB  - The polymorphism of the vascular endothelial growth factor (VEGF) -634C/G has
      been correlated with susceptibility to osteonecrosis of the femoral head (ONFH).
      The aim of this study was to derive a more precise estimation of the relationship
      between the VEGF -634C/G polymorphism and ONFH by performing a meta-analysis. We
      searched articles indexed in Pubmed, OVID and Web of Science published up to
      January 2015 that met our predefined criteria. The strength of the association
      between VEGF -634C/G polymorphism and ONFH risk was assessed by an odds ratio
      (OR) with the corresponding 95% CI. Three eligible studies involving 692 cases
      and 875 controls were identified. Overall, pooled analysis indicated a
      significant association between VEGF -634C/G polymorphism and ONFH risk (for C
      vs. G: OR=1.141, 95% CI 1.055-1.235, P=0.001; for CC vs. GG: OR=1.345, 95% CI
      1.124-1.610, P=0.001; for CG vs. GG: OR=1.106, 95% CI 1.018-1.202, P=0.017; for
      CG+CC vs. GG: OR=1.104, 95% CI 1.035-1.177, P=0.003; for CC vs. GG+ CG: OR=1.294,
      95% CI 1.051-1.593, P=0.015). No evidence of publication bias was observed. In
      conclusion, this meta-analysis suggested that polymorphism of VEGF -634C/G was a
      risk factor for ONFH. This finding needs further confirmation by trans-regional
      multicenter study with large sample in different ethnic populations, such as
      Caucasian and Austroloid. 

PMID- 26309591
TI  - Impacts of K562 cells towards activities of Toll-like receptor pathway of human
      mesenchymal stem cell-bone marrow.
AB  - The study aim was to investigate the impacts of K562 cells towards the activities
      of Toll-like receptor pathway of human mesenchymal stem cell-bone marrow (HMSC
      bm). The in vitro co-culture of HMSC-bm and K562 cells was set as the experiment
      group (HMSC-bm + K562), the HMSC-bm cultured alone was set as the control group
      (HMSC-bm), the expressions of six interested genes and their proteins, namely
      MyD88, P38, NF-kappaB, TAB1, TLR3 and TBK1, of the Toll -like receptor signaling
      pathway were detected and compared, as well as the secretions of such cytokines
      as IL-6, IL-8, TNF-alpha and IFN-alpha in the cell supernatant, which were
      regulated by the Toll-like receptor pathway. The expressions of MyD88, P38, TAB1
      and TLR3 of the HMSC-bm + K562 group were higher than the HMSC-bm group, while
      that of TBK1 was lower, and the NF-kappaB expression showed no significant
      difference between the two groups (P > 0.05). Compared with the HMSC-bm group,
      the supernatant of HMSC-bm + K562 group exhibited the higher secretion levels of
      IL-6 and IL-8, while that of IFN-alpha was just contrary, and the differences
      were significant (P < 0.05). The secretion levels of TNF-alpha within the two
      groups were not significantly different (P > 0.05). The co-culture of K562 and
      HMSC-bm could induce the activity changes of Toll-like receptor pathway of HMSC
      bm, which was beneficial towards the proliferation of K562 cells. 

PMID- 26309592
TI  - Cytotoxicity evaluation of five different dual-cured resin cements used for fiber
      posts cementation.
AB  - Custom-cast posts and cores are usually used to treat endodontically treated
      teeth. However, several researches have underlined how these devices may be a
      much higher elastic modulus than the supporting dentine and the difference in the
      modulus could lead to stress concentrating in the cement lute, leading to
      failure. The role of the cement seems to play a fundamental role in order to
      transfer the strength during the chewing phases. Aim of this research is to
      record the rate of cytotoxicity of five different dual-cured resin cements used
      for fiber posts cementation. We tested the cytotoxicity of this five materials on
      MG63 osteoblast-like cells through two different methods: MTT ([3-4,5
      dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide succinate) assay which
      tests for mitochondrial enzyme activity(6) and xCELLigence(r) system. 

PMID- 26309593
TI  - Unilateral vagus nerve stimulation improves ventricular autonomic nerve
      distribution and functional imbalance in a canine heart failure model.
AB  - BACKGROUND: Chronic heart failure (HF) is the main complication of various
      organic heart diseases. An imbalance of the autonomic nervous system has close
      associations with arrhythmia, ventricular remodeling, and sudden death upon HF.
      This study investigated whether unilateral vagus nerve stimulation could increase
      vagal activity, improve autonomic nerve distribution, and cardiac function in a
      HF model. METHODS: Eighteen dogs were randomly divided into 3 groups: sham
      operation, HF, and HF + vagal stimulation, with 6 dogs per group. The sham
      operation group had a pacemaker implanted, with no pacing; the HF group was
      tachypaced at 50 times/min for 37 d to establish the (chronic or congestive) HF
      model; Vagal stimulation group were implanted with a pacemaker at 250 times/min
      rapid pacing for 30 d, then the right vagus nerve was stimulated for 7 d
      (frequency: 20 Hz). Left ventricular ejection fraction (LVEF) and mean arterial
      pressure (MAP) were examined with an ultrasound diagnostic apparatus. Resting
      heart rate was recorded with an electrocardiogram monitor. The expression of
      tyrosine hydroxylase (TH) and choline acetyl-transferase (ChAT) protein was
      examined by immuno-histochemistry. RESULTS: 30 d after rapid ventricular pacing,
      MAP < 60 mm Hg, and LVEF < 50%, the HF model was successfully established in
      canines. The results showed that there were no differences in MAP, LVEF, and
      resting heart rate at baseline in each group (P > 0.05). After 30 d of pacing,
      MAP and LVEF were reduced and resting heart rate increased in the HF and HF +
      vagal stimulation group compared to the sham operation group (P < 0.05). After 37
      d, compared with the sham operation group, MAP and LVEF were significantly
      reduced and resting heart rate significantly increased in HF group (P < 0.05).
      Compared with the sham operation group, TH and ChAT positive nerve density
      heterogeneity increased in the HF group but did not change in the HF + vagal
      stimulation group. TH protein expression was increased and ChAT protein
      expression reduced in the HF group; TH expression decreased and ChAT expression
      increased in the HF + vagal stimulation group. CONCLUSION: Unilateral vagus nerve
      stimulation increased vagus nerve activity, slowed heart rate, recovered
      autonomic nerve homogeneity and function imbalance, and improved heart function
      in HF.

PMID- 26309594
TI  - CD192 gene variant and susceptibility to cervical cancer: a meta analysis.
AB  - BACKGROUND: Several molecular epidemiological studies have explored the
      association between G46295A variant of CD192 gene and cervical cancer
      susceptibility in distinct populations. However, the results are contradictory.
      To provide convincing evidence for the association, we performed the present meta
      analysis incorporating all case-control studies. METHODS AND FINDINGS: The
      Cochrane, Google Scholar and PubMed databases were systematically searched to
      identify the potentially relevant studies. Statistical analyses were performed
      using R software. Crude odds ratio (OR) was calculated to estimate the risk of
      cervical cancer. Five case-control studies were considered in the final analysis.
      Using the homozygous, heterogeneous, allele, dominant, and recessive model, we
      found the association between CD192 G46295A variant and cervical cancer was not
      statistically significant. CONCLUSIONS: This meta-analysis shows that the CD192
      G46295A variant may not confer genetic susceptibility towards cervical cancer.

PMID- 26309595
TI  - Spinal cord injury in rats treated using bone marrow mesenchymal stem-cell
      transplantation.
AB  - The aim of this study was to observe the effects of bone marrow mesenchymal stem
      cell transplantation (BMSCs) in repairing acute spinal cord damage in rats and to
      examine the potential beneficial effects. 192 Wistar rats were randomized into 8
      groups. Spinal cord injury was created. Behavior and limb functions were scored.
      Repairing effects of BMSCs transplantation was evaluated and compared. In vitro
      4',6-diamidino-2-phenylindole (DAPI)-tagged BMSCs were observed, and whether they
      migrated to the area of spinal cord injury after intravenous tail injection was
      investigated. The expression of neuron-specific protein (NSE) on BMSCs was
      examined. Fifteen days after transplantation, the BMSCs-treated groups scored
      significantly higher in limb function tests than the untreated group.
      Pathological sections of the bone marrow after operation showed significant
      recovery in treated groups in comparison to the control group. After
      transplantation, small amounts of fluorescent-tagged BMSCs can be found in the
      blood vessels in the area of spinal cord injury, and fluorescent-tagged BMSCs
      were diffused in extravascular tissues, whereas the DAPI-tagged BMSCs could not
      be detected,and BrdU/NSE double-labeled cells were found in the injured marrow.
      BMSCs improve behavioral responses and can repair spinal cord injuries by
      migrating to the injured area, where they can differentiate into neurons. 

PMID- 26309596
TI  - Association between TCF7L2 polymorphisms and breast cancer susceptibility: a meta
      analysis.
AB  - AIM: Our aim was to investigate the relationship between transcription factor 7
      like 2 (TCF7L2) polymorphisms and breast cancer susceptibility. METHODS: PubMed,
      Embase and CNKI databases were used to search the related studies investigating
      the correlation between TCF7L2 polymorphisms and breast cancer susceptibility.
      Pooled ORs and 95% CIs, based on five genetic models, were applied to estimate
      the association betweenTCF7L2 polymorphisms and breast cancer. A fixed-effect
      model or a random-effect model was applied according to the between-study
      heterogeneity. RESULTS: We analyzed six single nucleotide polymorphisms (SNPs) in
      TCF7L2 gene, namely rs12255372, rs7903146, rs7900150, rs3750805, rs1225404 and
      rs7003146. The increased risk of breast cancer was associated with TCF7L2
      polymorphisms (22 vs. 11: OR=1.16, 95% CI=1.02-1.32; 22+12 vs. 11: OR=1.06, 95%
      CI=1.02-1.10; 22 vs. 11+12: OR=1.15, 95% CI=1.04-1.27; 2 vs. 1: OR=1.07, 95%
      CI=1.02-1.13; 12 vs. 11: OR=1.05, 95% CI=1.01-1.09). Among the locus, rs7903146
      polymorphism was significantly associated with the risk for breast cancer under
      five genetic models (TT vs. CC: OR=1.29, 95% CI=1.08-1.53; TT+CT vs. CC: OR=1.09,
      95% CI=1.01-1.18; TT vs. CC+CT: OR=1.24, 95% CI=1.05-1.48; T vs. C: OR=1.11, 95%
      CI=1.04-1.19; CT vs. CC: OR=1.08, 95% CI=1.00-1.17). Additionally, rs7900150 also
      showed effects on the susceptibility of breast cancer (TT vs. AA: OR=1.22, 95%
      CI=1.07-1.39; TT+AT vs. AA: OR=1.06, 95% CI=1.00-1.14; TT vs. AA+AT: OR=1.21, 95%
      CI=1.07-1.37; T vs. A: OR=1.09, 95% CI=1.02-1.15; AT vs. AA: OR=1.04, 95% CI=1.01
      1.33). Meanwhile, we found that rs3750805 polymorphism could increased the risk
      for breast cancer (TT+AT vs. AA: OR=1.12, 95% CI=1.01-1.24). CONCLUSION: Our meta
      analysis demonstrates that TCF7L2 polymorphisms may increase the risk for breast
      cancer.

PMID- 26309598
TI  - Imaging manifestations and diagnosis of a case of adult cerebral paragonimiasis
      with the initial symptom of hemorrhagic stroke.
AB  - This study is to investigate the clinical features, neuroimaging and diagnosis of
      adult cerebral paragonimiasis. One case of patient with cerebral paragonimiasis
      as retrospectively analyzed in this study. Analysis included medical history,
      clinical manifestations and neuroimaging. Blood test, body fluid examination,
      immunological test, stool examination and imaging examination were performed.
      Many symptoms such as headache, hemiplegia, chest pain, cough, and pleural
      effusion were detected in the patient. The features of "tunnel-like shape" and
      "ring-like shape", the intracranial hemorrhage and edema were shown by CT and MRI
      imaging. Chest CT examination revealed pleural effusion. Eosinophil count of
      peripheral blood and pleural effusion increased. Lung fluke ELISA test was
      positive and anti-parasitic treatment was effective. The typical clinical
      manifestations of MRI of cerebral paragonimiasis, such as the "tunnel-like shape"
      and "ring-like shape", were of high diagnostic value. And, blood eosinophil count
      examination and paragonimiasis antibody test could also help the diagnosis value.

PMID- 26309597
TI  - Application of stent-graft is the optimal therapy for traumatic internal carotid
      artery pseudoaneurysms.
AB  - BACKGROUND: Traumatic pseudoaneurysm of the internal carotid artery (ICA) is an
      uncommon but serious complication, and difficult to repair surgically. Minimally
      invasive endovascular treatment of traumatic injuries of the ICA with a stent
      graft has become increasingly popular over the past decade. The efficacy of the
      stent graft appears satisfactory, but most if not all reported studies have
      involved small patient cohorts (less than 10) with short follow-up periods (less
      than 3 years). METHODS: In this prospective study, 13 patients with traumatic
      pseudoaneurysm of the ICA were recruited from June 2008 to June 2012. All the
      patients were examined using whole-brain cerebral angiography and followed up for
      as long as five years. Willis intracranial vascular stent grafts, manufactured by
      Shanghai Microport, were chosen as embolism material. RESULTS: All 13 patients
      achieved good clinical outcome. Pseudoaneurysm recurred in one patient and this
      patient was treated by balloon occlusion of the parent artery. No patient
      suffered recurrent bleeding or death. CONCLUSION: Based on the outcomes of this
      relatively large cohort and long follow-up period, we believe that stent graft is
      an optimal therapy for patients with traumatic pseudoaneurysms of the ICA.

PMID- 26309599
TI  - Clinical analysis and prognostic significance of L-asparaginase containing
      multidrug chemotherapy regimen in incipient peripheral T-cell lymphoma.
AB  - OBJECTIVE: To observe the clinical effects and adverse reactions, and analyze the
      clinical significance of L-asparaginase (L-ASP) containing multidrug chemotherapy
      regimen in incipient peripheral T-cell lymphoma (PTCL). METHODS: A retrospective
      analysis was conducted of 102 patients with incipient PTCL who received L-ASP
      containing multidrug chemotherapy regimens or not in our hospital from January
      2010 to December 2013. Complete remission (CR) rate, partial remission (PR) rate,
      overall remission (OR) rate, progression free survival (PFS), overall survival
      (OS) and adverse reactions were compared. RESULTS: Patients who received L-ASP
      containing multidrug chemotherapy (L-ASP group) had higher OR rate than those who
      received L-ASP-free ones (non L-ASP group) (83.3% vs 61.7%, P=0.016),
      particularly those at phase III/IV (82.4% vs 54.0%, P=0.007) and with an
      international prognostic index (IPI) score of >=2 (82.1% vs 50.0%, P=0.006). The
      median survival time (OS) was 10.5 months (range, 1-47months) in L-ASP group,
      while 13 months (range, 0.3-68 months) in non L-ASP group, and they had no
      statistically significance (P=0.754). Similarly, the progression free survival
      time(PFS)was 10 months (range, 1-47 months) in L-ASP group,while 11 months
      (range, 0.3-68 months) in non L-ASP group, also had no statistically significance
      (P=0.414). The 3-year OS rate of L-ASP group and non L-ASP group were 48.9% and
      65.0% , respectively (P=0.974) and the 3-year PFS rate of L-ASP group and non L
      ASP group were 40.8% and 61.0%, respectively (P=0.479). They all had no
      statistically significance. The L-ASP group had more adverse reactions than the
      non L-ASP group, though most of them were mild and could be improved by
      symptomatic and supportive care. CONCLUSION: L-ASP containing multidrug
      chemotherapy regimen in incipient PTCL showed a better short-term effect and
      controllable adverse reactions. A large prospective clinical trial of use L-ASP
      in first-line treatment of PTCL is worthy of further research and investigation.

PMID- 26309601
TI  - Evaluation of serum sTWEAK and sCD163 levels in patients with acute and chronic
      coronary artery disease.
AB  - BACKGROUND: Recent studies have suggested soluble tumor necrotizing factor-like
      weak inducer of apoptosis (sTWEAK) and sCD163 may be a potential cardiovascular
      biomarker. We aimed to evaluate sTWEAK and sCD163 levels and predictive values in
      patients with chronic coronary artery disease (CAD) and acute coronary syndrome
      (ACS). METHODS: Two hundred fourteen angiography-made patients were enrolled in
      the study and divided into 3 groups: 30 controls with normal angiograms, 99
      patients with ACS, 85 patients with chronic CAD. sTWEAK, sCD163 and CRP levels
      were measured. Receivers operating characteristic (ROC) curve analysis were
      performed to determine the predictive values of sTWEAK and sCD163 levels and the
      sCD163/sTWEAK ratio. Gensini scores were used to assess severity of CAD. RESULTS:
      sTWEAK levels in chronic CAD and ACS patients were lower compared to the control
      group (P<0.0001). sCD163 levels (P<0.0001) and the sCD163/sTWEAK ratio (P<0.0001)
      were higher in the ACS patients compared to the control and chronic CAD patients.
      ROC analysis revealed low sTWEAK level and high sCD163/sTWEAK ratio predicted
      chronic CAD, and low sTWEAK, high sCD163, CRP levels and sCD163/sTWEAK ratio
      predicted ACS. According to ROC analyses, significance of sTWEAK levels for
      chronic CAD was more marked compared to ACS (P<0.0001 vs P=0.001) and
      significance of sCD163/sTWEAK ratio was greater than sTWEAK for ACS (P<0.0001 vs
      P=0.001). These parameters didn't correlate with severity of disease, obtained
      gensini scoring, in chronic CAD. CONCLUSIONS: It was concluded thatsTWEAK level
      may be a diagnostic marker of especially chronic CAD, sCD163 level of ACS, and
      the sCD163/sTWEAK ratio of both chronic CAD and ACS.

PMID- 26309600
TI  - Systematic tracking of dysregulated modules identifies disrupted pathways in
      narcolepsy.
AB  - OBJECTIVE: The objective of this work is to identify disrupted pathways in
      narcolepsy according to systematically tracking the dysregulated modules of
      reweighted Protein-Protein Interaction (PPI) networks. Here, we performed
      systematic identification and comparison of modules across normal and narcolepsy
      conditions by integrating PPI and gene-expression data. METHODS: Firstly, normal
      and narcolepsy PPI network were inferred and reweighted based on Pearson
      correlation coefficient (PCC). Then, modules in PPI network were explored by
      clique-merging algorithm and we identified altered modules using a maximum weight
      bipartite matching and in non-increasing order. Finally, pathways enrichment
      analyses of genes in altered modules were carried out based on Expression
      Analysis Systematic Explored (EASE) test to illuminate the biological pathways in
      narcolepsy. RESULTS: Our analyses revealed that 235 altered modules were
      identified by comparing modules in normal and narcolepsy PPI network. Pathway
      functional enrichment analysis of disrupted module genes showed 59 disrupted
      pathways within threshold P < 0.001. The most significant five disrupted pathways
      were: oxidative phosphorylation, T cell receptor signaling pathway, cell cycle,
      Alzheimer's disease and focal adhesion. CONCLUSIONS: We successfully identified
      disrupted pathways and these pathways might be potential biological processes for
      treatment and etiology mechanism in narcolepsy.

PMID- 26309602
TI  - Comparative study on induction and effects of surgical menopause in a female rat
      model: a prospective case control study.
AB  - OBJECTIVE: To compare induced surgical menopause in rat models following
      hysterectomy with ovarian preservation, unilateral or bilateral oophorectomy,
      versus control. Secondary objective was evaluation of certain physiological
      changes in the animal following the induced menopause. DESIGN: A prospective case
      control study. SETTING: University Research Centre. METHODOLOGY: 80 female rats
      were divided into four groups (n=20). HG: hysterectomy with ovarian preservation,
      UOG: unilateral oophorectomy, BOG: bilateral oophorectomy and CG: control rats.
      Blood tests were done at day 0, one week and one month post-procedure for
      hormonal profile including FSH and E2, and lipid profile including cholesterol,
      LDL and HDL. Behavioral tests (Learning and memory tests) were also done.
      RESULTS: Menopause was successfully induced by the three used surgical methods.
      After one week, no significant difference in FSH level between CG and HG. But its
      level was significantly increased in BOG and UOG. E2 level was significantly
      decreased in HG, UOG and BOG in comparison to CG. Its level in BOG was
      significantly lower than that of UOG and HG. Cholesterol level was significantly
      higher in HG, UOG and BOG in comparison to CG, also its level was significantly
      increased in UOG and BOG in comparison to HG (P<0.001). Long term memory was
      affected in BOG and UOG, one week and one month post-menopausal induction in
      comparison to the control. CONCLUSION: surgical menopause, induced by
      hysterectomy alone, unilateral, or bilateral oophorectomy has a negative impact
      on reproductive hormonal function, as well as cognitive & cardiovascular
      integrity. We suggest a possibility of early ovarian failure after hysterectomy
      alone or with unilateral oophorectomy.

PMID- 26309603
TI  - Diagnostic accuracy of myocardial deformation indices for detecting high risk
      coronary artery disease in patients without regional wall motion abnormality.
AB  - BACKGROUND: The prediction of coronary artery disease (CAD) by conventional
      echocardiographic measurements is principally based on the estimation of ejection
      fraction and regional wall motion abnormality (RWMA). This study aimed to
      determine whether strain echocardiography of left ventricle measured by velocity
      vector imaging (VVI) method could detect patients with a high-risk CAD. METHODS:
      In a prospective study, a total of 119 consecutive patients who were assessed for
      eligibility were categorized into three groups: (1) without CAD as normal (n=59),
      (2) 1- or 2-vessel disease as low-risk (n=29), and (3) left main and/or 3-vessel
      disease as high-risk (n=31). The peaks of systolic strain and strain rate from 18
      curves of apical views were averaged as global longitudinal strain and strain
      rate (GLS and GLSR), respectively; the 6 systolic peaks of strain and strain rate
      at base- and mid-ventricular of short axis views were averaged as mean radial
      strain rate (MRSR). RESULTS: GLS, GLSR, and basal MRSR of left ventricle were
      significantly lower in the high-risk group (P=0.047, P=0.004 and P=0.030,
      respectively). Receiver operating characteristics curve showed that the optimal
      values of GLS, GLSR, and basal MRSR for detecting the severe CAD were -17%, -1 s(
      1), and 1.45 s(-1) with the sensitivities of 77%, 71%, and 71% and the
      specificities of 63%, 67%, and 62%, respectively. CONCLUSION: Decrements in the
      GLS, GLSR, and basal MRSR of the left ventricle can detect the high-risk CAD
      cases among patients without RWMA at rest.

PMID- 26309604
TI  - Early diagnosis and treatment of trauma in knee joints accompanied with popliteal
      vascular injury.
AB  - OBJECTIVE: The objective of the present study was to investigate the early
      diagnosis and treatment of trauma in the knee joints accompanied with popliteal
      vascular injury. METHODS: Fifteen cases of patients with trauma in knee joints
      accompanied with popliteal vascular injury. These patients included 8 males and 6
      females between the ages of 27 and 62, the average age being 39.2. Data of
      clinical symptoms and signs; blood oxygen saturation, color Doppler examination;
      vascular intervention by DSA angiography; and surgical operations were analyzed
      to clearly identify their role in early diagnosis and treatment. RESULTS: In the
      patient group for this study there were: 1 death case; 4 stage I amputation
      cases; 4 stage II amputation cases due to failure to salvage limbs; and 6 cases
      with patients who had successful limb salvage. The six cases of limb survival
      patients were followed up for 12 to 60 months, with an average follow up time of
      28.3 months. The excellent rate of joint function of these patients with
      successful limb salvage was 83.3%. CONCLUSIONS: For patients with injured limbs,
      unclear dorsalis pedis artery palpation, decreased skin temperature, and
      decreased oxygen saturation of the toes, clinical manifestations combined with
      proper auxiliary inspection (such as color Doppler and blood vessel angiography
      of interventional DSA) enabled early diagnose of peripheral trauma in the knee
      joint accompanied with popliteal vascular injury.

PMID- 26309605
TI  - Association between genetic variants of DVWA and osteoarthritis of the knee and
      hip: a comprehensive meta-analysis.
AB  - Recently, double von Willebrand factor domain A (DVWA) gene, a previously unknown
      gene, was revealed to contain several single nucleotide polymorphisms (SNPs) that
      showed consistent association with knee osteoarthritis (OA) in Japanese and
      Chinese cohorts. However, subsequent studies failed to confirm this result in
      several different populations. To deal with the issues raised by inconsistent
      results among those studies, we investigated the association between DVWA and OA
      using meta-analytic techniques, combining all published data up to December 2014.
      10 independent samples from 4 teams contributed data for a possible association
      between SNP rs7639618 and knee or hip OA. The total number of cases and controls
      of this SNP was respectively 4,142 versus 6,575 for knee OA, and 2,325 versus
      2,914 for hip OA. A trend of significant association was observed in the combined
      population with knee OA (P=0.06), and a significant difference was identified
      between patients with knee OA and controls for the G-allele of rs7639618
      (P=0.02). Together with the reported functional studies, our results indicate
      that DVWA may have a small but strong effect on the susceptibility to knee OA, at
      least in Asian population. Further functional studies are needed to determine the
      underlying variation of DVWA and to relate this to the pathophysiology of OA. 

PMID- 26309606
TI  - Effect of methylphenidate on mismatched visual information processing in young
      healthy volunteers: an event-related potential study.
AB  - This study was to investigate whether a single dose of methylphenidate (MPH), a
      dopamine and noradrenaline enhancing drug for the treatment of attentional
      deficits, influences mismatch visual information processing in young healthy
      volunteers determined with N270. A randomized double-blinded placebo-controlled
      study was conducted, and each participant was tested on two sessions separated by
      two weeks. On each session, a matching task was given first, followed by taking
      an opaque capsule (20 mg MPH or placebo), and matching task was administered
      again after 90-min rest. There were two kinds of visually presented stimulus
      pairs in this task: in the matched condition, the second stimulus (S2) in a pair
      was identical to the first one (S1); in the mismatched condition, S2 differed
      from S1 in the color, global shape and direction of the figure. Subjects were
      asked to press a button in the matched condition and another button in the
      mismatched condition. Scalp event-related potential were recorded simultaneously.
      In the matched condition, P300 was elicited by S2; in the mismatched condition,
      N270 was also elicited by S2 before P300 stimulation. Results showed MPH
      shortened the latency of N270 and P300 suggesting that a single low dose of MPH
      promotes the information processing at several stages including conflict
      processing and working memory updating. 

PMID- 26309607
TI  - Personalised lamellar keratoplasty and keratopigmentation in Asian corneal
      leucoma patients.
AB  - OBJECTIVE: To describe a personalised lamellar keratoplasty (LK) associated with
      the keratopigmentation (KTP) technique for corneal leucoma among Asian patients.
      METHODS: This report was a non-randomised, retrospective clinical study performed
      in 32 consecutive eyes of 32 patients to improve cosmetic appearance. Twenty-two
      patients underwent LK combined with KTP, either by intralamellar or superficial
      route. Ten patients underwent the single personalised keratopigmentation method.
      The subjective and objective cosmetic results, ocular irritation, colour fading,
      neovascularisation formation and incidence of immune rejection were evaluated
      until three years after surgery. RESULTS: No complications occurred, and the
      corneal leucoma was successfully stained with India ink in all 32 patients. Most
      of the patients showed good cosmetic appearance. Pain, conjunctival congestion,
      corneal edema and foreign body sensation disappeared gradually within two to
      three weeks after surgery in all patients. Graft swelling, non-healing, or
      detaching was not observed during follow-up. However, two patients had slight
      opacity three years after LK. Colour fading was observed in one patient who
      underwent intralamellar corneal staining 10 months after surgery. Re-staining was
      performed. CONCLUSION: KTP combined with personalised LK is an effective
      personalised technique that presents long-standing colour staining and good
      cosmetic efficacy.

PMID- 26309608
TI  - Auxiliary diagnostic value of monocyte chemoattractant protein-1 of whole blood
      in active tuberculosis.
AB  - The aim of this study was to study the expression level of interferon-gamma (IFN
      gamma) and monocyte chemoattractant protein-1 (MCP-1) in peripheral blood and its
      auxiliary diagnostic value in active tuberculosis. A chemiluminescence enzyme
      immunoassay method was used to detect the levels of IFN-gamma and MCP-1 in
      peripheral blood. Then the receiver operating characteristic curve were drawn to
      determine the threshold of IFN-gamma and MCP-1 for diagnosis of active
      tuberculosis and to evaluate their diagnostic performance. The specific IFN-gamma
      and MCP-1 levels in the active tuberculosis group were significantly higher than
      those in the non-tuberculous pulmonary disease group (P < 0.01) and those in the
      healthy control group (P < 0.01). The IFN-gamma levels in the healthy control
      group and the non-tuberculous respiratory disease group showed no statistically
      significant difference (P > 0.05), but the MCP-1 levels in the non-tuberculous
      respiratory disease group were significantly higher than those of the healthy
      control group (P < 0.05). The specific IFN-gamma and MCP-1 level cut off values
      were 256 pg/ml and 389 pg/ml as an active tuberculosis diagnostic standard. The
      sensitivities of IFN-gamma and MCP-1 were 57.3% and 92.8%, respectively;
      specificities were 80% and 80.7%, respectively; the positive predictive values
      were 76.9% and 84.9%, respectively; negative predictive values were 61.7% and
      78.7%, respectively; and accuracy rates were 76.9% and 84.9%, respectively.
      Compared with the detection of IFN-gamma, we observed a better diagnostic
      performance of MCP-1 in peripheral blood in active tuberculosis. MCP-1 may become
      one of the active tuberculosis auxiliary diagnostic targets. 

PMID- 26309609
TI  - Prevalence of multidrug resistant Gram-positive cocci in a Chinese hospital over
      an 8-year period.
AB  - Gram-positive cocci are common causes of bloodstream and nosocomial infections,
      and their multi-drug resistance is an increasingly serious problem. The present
      study aimed to assess the prevalence of multi-drug-resistant Gram-positive cocci
      in a Chinese population. In this retrospective study, data about Gram-positive
      cocci from in-patients (January 2006 and December 2013) at the Second Hospital of
      Shanxi Medical University, Taiyuan, China, were reviewed. Antimicrobial
      susceptibility profile of the isolated Gram-positive cocci was evaluated using
      the disk diffusion method. Antibiotic resistance was determined according to the
      Clinical and Laboratory Standards Institute 2009 guidelines. The prevalence of
      drug resistance was determined, as well as correlation coefficients for various
      drugs between the resistance rate and year of sample collection. A total of 7789
      Gram-positive cocci isolates were found, including 2576 (33%) coagulase-negative
      Staphylococci, 1477 (19%) Staphylococci aureus, 1343 (17%) Enterococcus faecalis,
      and 1139 (15%) Enterococcus faecium. The proportions of methicillin-resistant
      Staphylococci aureus (MRSA) and methicillin-resistant Staphylococci (MRS) were
      31.5% (465/1477) and 61.6% (1587/2576), respectively. Among all isolates, MRS had
      much higher drug resistance rate than methicillin-sensitive Staphylococci
      (P<0.05). E. faecalis had a higher multi-drug resistance rate than E. faecium
      (P<0.01). Interestingly, MRSA resistance rates declined over the years, showing a
      negative correlation coefficient for all drugs, with significance for
      levofloxacin, azithromycin, erythromycin, and clindamycin (P<0.05), but not
      sulphamethoxazole/trimethoprim (P=0.057) and gentamicin (P=0.186). These results
      indicated that Staphylococci were the predominant Gram-positive cocci isolated.
      There was a trend of decreasing MRSA in the population studied. 

PMID- 26309610
TI  - Protective effect of the omega-3 polyunsaturated fatty acids on the
      schistosomiasis liver fibrosis in mice.
AB  - This study aims to observe the effect of omega-3 polyunsaturated fatty acids on
      initiation and elimination of the schistosomiasis inflammatory response and liver
      fibrosis. The mice infected with the cercariae of Schistosoma japonicum (20 +/-
      cercarie per mice) were separated randomly into several groups. After 60 days,
      liver tissue samples of all mice were sectioned. Hematoxylin-eosin (HE) staining,
      Masson staining, the enzyme-linked immunosorbent assay (ELISA), and flow
      cytometry (FCM) were performed. Through HE and Masson staining, the size of egg
      (ovum) granuloma and the collagen deposited in mice's livers in omega-3 PUFAs and
      praziquantel mixed groups were less than that of model group and praziquantel
      treated group. The serum level of IL-13 and TNF-alpha were lower than that of
      model group and praziquantel treated group. The indicators of liver fibrosis,
      such as HA and LN in the group treated with omega-3 PUFAs and praziquantel before
      the release of soluble eggs antigen (SEA) into blood, were lower than that of
      model group and praziquantel treated group, respectively. The combined treatment
      of omega-3 polyunsaturated fatty acids and praziquantel conducted before the
      release of soluble eggs antigens into the blood decreases liver ovum
      granulomatous inflammation and fibrosis degree in the schistosomiasis. The
      mechanism of the omega-3 polyunsaturated fatty acid may be related to the
      adjustment of the anti-inflammatory and immune responses. 

PMID- 26309611
TI  - The value of ratio of hCG, progesterone in local blood of pregnancy location
      versus venous blood in the diagnosis of ectopic pregnancy.
AB  - OBJECTIVE: The aim of this study is to combine the ratios of venous
      serum/colporrhagia and hemoperitoneum/venous serum of human chorionic
      gonadotropin (hCG) and Progesterone (P) to generate and evaluate a new method to
      improve the prognosis of Ectopic pregnancy (EP). METHODS: For patients with
      curettage procedure, curettage material and venous blood were obtained at the
      same time. For patients receiving culdocentesis and laparoscopic exploration,
      abdominal fluid and venous blood samples were obtained synchronously during
      surgery. RESULTS: The sensitivity and specificity of Rp/v-hCG>1.0 and Rp/v-P>1.0
      for diagnosis of EP was 88.2% and 80.71%, 93.8% and 87.53%, respectively. The
      sensitivity of parallel test (Rp/v-hCG>1.0 or Rp/v-P>1.0) was 92.23%. The
      specificity of serial test (Rp/v-hCG>1.0 and Rp/v-P>1.0) was 100%. For the area
      under the ROC curve of Rp/v-hCG and Rp/v-P, the parallel test and serial test
      were 0.91 and 0.82,0.90 and 0.87, respectively. At the determining threshold
      point of 1.0, the sensitivity of Rv/c-hCG and Rv/c-P for the diagnosis of EP was
      56.73% and 60.01%. The specificity was 100% and 100%, respectively. The
      sensitivity of parallel test (Rv/c-hCG>1.0 or Rv/c-P>1.0) was 73.33%. For the
      area under the ROC curve of Rv/c-hCG, Rv/c-P and the parallel test was 0.78,0.80
      and 0.87, respectively. CONCLUSIONS: It is proposed that EP can more rapidly and
      accurately be diagnosed by multiple biomarkers' test of Rp/v-hCG>1.0 and/or Rp/v
      P>1.0, as well as Rv/c-hCG>1.0 and/or Rv/c-P>1.0 via culdocentesis or curettage.

PMID- 26309612
TI  - Morphological study of the pterygoid canal with high-resolution CT.
AB  - The purpose of our study was to accurately visualize and measure the normal
      anatomy and size of the pterygoid canal with thin-section (0.5 mm), high
      resolution computed tomography (HRCT) as well as multiplanar reconstruction (MPR)
      and curved planar reconstruction (CPR) technologies to obtain credible and
      comprehensive information for clinical management. Both axial HRCT and MPR images
      of the pterygopalatine fossa were obtained in 167 normal adult subjects, who
      exhibited variable positions of pterygoid canal relative to the sphenoid sinus
      floor and cavity. The morphology and size of the pterygoid canal was observed and
      measured, respectively. All pterygoid canals (100%, 334/334) were well delineated
      on HRCT images. Statistical analyses showed no significant difference between the
      mean length of the left (12.6 +/- 2.3 mm) and right pterygoid canals (12.5 +/-
      2.9 mm) (P = 0.405). The mean diameter of anterior, median and posterior opening
      of the left and right pterygoid canals exhibited no significant differences (all
      P > 0.05); the bilateral median opening possessed the smallest diameter (P <
      0.001). Submillimeter, thin-section HRCT scan and appropriate postprocessing
      reconstruction technologies could clearly visualize the morphologic features of
      the pterygoid canal and adjacent structures, which may be helpful for making
      diagnostic and therapeutic decisions. 

PMID- 26309613
TI  - An indicator of subclinical cardiovascular disease in patients with primary
      osteoarthritis: epicardial fat thickness.
AB  - Osteoarthritis (OA) is one of the most common chronic diseases seen in the
      elderly, and it is associated with increased cardiovascular morbidity and
      mortality. The cause of this association is not fully known. We aimed to
      investigate the relationship between epicardial fat and the presence and the
      grade of primary knee OA for analyzing the relationship between visceral
      adiposity and primary OA, thereby revealing the increased subclinical
      atherosclerosis and cardiovascular risk in OA patients. In this cross-sectional
      study, subjects with primary knee osteoarthritis and a control group were
      compared with regard to epicardial fat thickness through transthoracic
      echocardiography. In addition, OA was divided into four stages and the
      relationship between the grade of OA and epicardial fat thickness was analyzed.
      Eighty subjects with primary knee OA and 50 controls were analyzed. There was no
      difference between groups with regard to age, gender and BMI. Epicardial fat
      thickness was greater in patients in the primary OA group compared to the control
      group (3.73+/-1.08 vs 3.30+/-0.61, respectively, P=0.005). In-group comparison of
      OA patients revealed that epicardial fat thickness was detected to increase as
      the grade of OA increased (P=0.001). A relationship was detected between the
      presence of OA and epicardial fat thickness and CRP levels in multivariate
      logistic analysis (P=0.017, P=0.047, respectively). There is a significant
      relationship between primary OA and epicardial fat thickness, which is a part of
      visceral adipose tissue. These results may indicate the relationship between OA
      and visceral fat tissue and, consequently, cardiovascular risk, so body weight
      alone may not be an identifying co-factor. 

PMID- 26309614
TI  - Serum neuron specific enolase levels correlate with patient prognosis for
      advanced lung cancer.
AB  - To analyze the clinical and prognostic value of neuron specific enolase (NSE)
      levels in serum of advanced lung cancer patients, we analyzed serum NSE level of
      110 advanced lung cancer patients (case group), 100 benign lung disease patients
      (benign disease group), and 100 healthy persons (control group). Case group
      patients were divided by NSE level into >=25 ng/mL (52 cases) and <25 ng/mL (58
      cases) groups to analyze overall survival (OS) and progression-free survival
      (PFS). The results showed the serum NSE levels of case group patients were
      significantly higher than those of control or benign disease group patients
      (P<0.05). Serum NSE levels of small cell lung cancer patients were significantly
      higher than those of patients with other tumor pathologies (all P<0.05). Median
      OS significantly differed between patients with NSE levels >=25 ng/mL (23.7
      months) and <25 ng/mL (31.4 months) (P<0.05). Median PFS also significantly
      differed between patients with NSE levels >=25 ng/mL (13.5 months) and <25 ng/mL
      (17.6 months) (chi (2)=9.992; P<0.05). Tumor pathology (RR=4.136), patient
      performance status score (RR=2.903), and serum NSE level (RR=2.338) were factors
      influencing OS (P<0.05). Patient performance status score (RR=2.903), number of
      chemotherapy lines (RR=1.776), and serum NSE level (RR=2.075) were influencing
      factors in patients' PFS (P<0.05). In brief, serum NSE level significantly
      correlates with advanced lung cancer patient prognosis and may be useful as an
      auxiliary index to predict prognosis. 

PMID- 26309615
TI  - The association study on renalase polymorphism and hypertension: a meta-analysis.
AB  - Hypertension is considered a multi-factorial disease since its development is
      affected by both genetic and environmental factors. Intensive efforts have been
      focused on identifying gene(s) related to hypertension. Renalase is a recently
      discovered protein that expressed in kidney, heart, liver, and brain that
      metabolizes catecholamines, regulation of blood pressure in humans and animals. A
      common missense polymorphism in the flavin-adenine dinucleotide-binding domain of
      human renalase (Glu37Asp) has recently been described. But the reported results
      are not always consistent. In this meta-analysis, we examined the association
      between (Glu37Asp) polymorphism (rs2296545) in renalase gene and risk of
      hypertension. Through a systematic literature search for publications between
      2007 and 2014, we summarized the data from 4 studies on polymorphism (rs2296545)
      in renalase gene and risk of hypertension. We did not find any association of
      rs2296545 with risk of hypertension in dominant model (OR=0.64; 95% CI: 0.41
      1.00), recessive model (OR=1.29, 95% CI: 0.95-1.75), co-dominant model (OR=1.38,
      95% CI: 0.92-2.08), and allelic model (OR=1.19; 95% CI: 0.96-1.47). The results
      of the present study indicated that the renalase genetic polymorphism was not
      associated with risk of hypertension. 

PMID- 26309616
TI  - Surgical diagnosis and treatment of primary hyperparathyroidism: analysis of 19
      cases.
AB  - This study was to discuss the surgical diagnosis and treatment experience of
      primary hyperparathyroidism. Clinical data of 19 primary hyperparathyroidism
      patients who were treated surgically in our department from Jan. 2005 to Jul.
      2014 were retrospectively analyzed. Besides, general data, clinical
      manifestations, laboratory and imaging test results, surgical procedures and
      postoperative follow-up information were comprehensively analyzed. 15 of 19
      patients had adenoma, among whom 1 case was complicated with goiter, 3 cases with
      parathyroid hyperplasia, and 1 case with parathyroid carcinoma. One case of
      bilateral parathyroid adenoma was explored bilaterally, and the bilateral
      parathyroid adenoma was excised. 14 cases of unilateral parathyroid adenoma were
      explored unilaterally and the unilateral parathyroid adenoma was excised. 3 cases
      of parathyroid hyperplasia were explored bilaterally, and parathyroid glands were
      removed subtotally, and only half gland was reserved. 1 case of parathyroid
      carcinoma experienced excision of thyroid gland and parathyroid at the affected
      side and isthmus excision, subtotal excision of thyroid gland at the healthy side
      and functional cervical lymphonode dissection at the affected side. All the 19
      cases recovered well after operation, and symptoms of hyperparathyroidism were
      controlled. No relapse was found after follow-up of 3 months to 5 years. In
      conclusion, local parathyroid excision with small wounds after pre-operative
      locative image test and qualitative laboratory test is effective. Timely surgical
      treatment could reduce joint and urinary damage. Post-operative follow-up should
      be emphasized for early detection of the patients with hypoparathyroidism and
      recurrence. 

PMID- 26309617
TI  - Comparison of venous drainage in flow-through and conventional dorsalis pedis
      flaps for repair of dorsal foot defects.
AB  - Inadequate venous drainage can lead to congestion and necrosis of flaps used in
      the repair of defects, thereby elevating the risk of flap failure. In this study,
      we sought to test the hypothesis that the venous drainage was better in flow
      through flaps than in conventional dorsalis pedis free flaps used in the repair
      of dorsal foot defects. In this retrospective study, we investigated the data of
      14 patients who underwent repair with flow-through flaps (n = 7) or conventional
      flaps (n = 7) for dorsal foot defects, between January 2007 and December 2013.
      The defects ranged from 6.2 * 11 cm to 9.5 * 16 cm in size. The donor sites were
      resurfaced using full-thickness free-skin grafts, and after transfer, the flaps
      were evaluated for postoperative congestion, surviving area, and sensory
      function. The results showed that the operative time was significantly longer for
      flow-through flaps than for conventional flaps (6.4 +/- 1.7 h vs. 4.3 +/- 1.2 h,
      P = 0.020), mainly due to additional dissection of the first dorsal metatarsal
      artery required in the case of the former. Necrosis was observed in the case of 4
      conventional flaps, but not in the case of flow-through flaps. The flow-through
      flaps showed significantly lower incidence of congestion and higher survival area
      proportion than the conventional flaps (P < 0.05). The flow-through dorsalis
      pedis flaps have the advantages of lower incidence of necrosis and congestion and
      better survival over the conventional flaps in the repair of dorsal foot defects,
      and absence of additional morbidities, but required a longer operative time than
      conventional flaps. 

PMID- 26309618
TI  - Detection of fetal cell-free DNA in maternal plasma for Down syndrome, Edward
      syndrome and Patau syndrome of high risk fetus.
AB  - OBJECTIVE: The study aimed to validate the efficacy of detection of fetal cell
      free DNA in maternal plasma of trisomy 21, 18 and 13 in a clinical setting.
      METHODS: A total of 2340 women at high risk for Down syndrome based on maternal
      age, prenatal history or a positive sesum or sonographic screening test were
      offered prenatal noninvasive aneuploidy test. According to the prenatal
      noninvasive aneuploidy test, the pregnant women at high risk were offered
      amniocentesis karyotype analysis and the pregnant at low risk were followed up to
      make sure the newborn outcome. RESULTS: The prenatal noninvasive aneuploidy test
      was positive for trisomy 21 in 17 cases, for trisomy 18 in 6 cases and for
      trisomy 13 in 1 case, which of all were confirmed by karyotype analysis. Newborns
      of low risk gestational woman detected by prenatal noninvasive aneuploidy for
      trisomy 21, 18, 13 were followed up and no one was found with trisomy.
      CONCLUSIONS: The prenatal noninvasive aneuploidy test is highly accurate for
      detection of trisomy 21, 18 and 13, which can be considered as a practical
      alternative for traditional invasive diagnostic procedures.

PMID- 26309619
TI  - Test of 259 serums from patients with arthritis or neurological symptoms
      confirmed existence of Lyme disease in Hainan province, China.
AB  - Indirect Fluorescent-Antibody Test (IFA), Western Blot (WB) and Nested-PCR were
      applied to identify the Borrelia burgdorferi in human serum samples in Hainan
      province. A total of 259 serum samples were collected from Sanya Peoples'
      Hospital, Hainan province. These samples were examined for the presence of B.
      burgdorferi serologically and etiologically by the two tier tests (IFA and WB)
      and Nested-PCR. 43 in total of 259 serum samples were tested positive by IFA
      assay, the positive rate was 16.6%. Among 43 IFA-positive samples, 6 were
      identified positive by WB. Nested-PCR were also used to test B. burgdorferi DNA
      in 259 serum samples at the same time, 27 samples were tested positive with
      positive rate of 10.42%. It is the first time to confirm that there are Lyme
      patients in Hainan province of China. The study suggested that Lyme disease
      should be commonly considered by clinicians with the patients who had correlated
      symptoms with lyme disease in Hainan. 

PMID- 26309620
TI  - Retrospective study of cytomegalovirus retinitis complicated with acquired
      immunodeficiency syndrome.
AB  - PURPOSE: This study was designed to explore the characteristics and therapy of
      cytomegalovirus retinitis (CR) in patients diagnosed with acquired
      immunodeficiency syndrome (AIDS). METHODS: A total of 67 AIDS patients (78 eyes)
      with CR findings of were collected from January 2009 to January 2013. The
      correlation between CR, cellular immunity, risk factor, clinical characteristics,
      treatment and prognosis of CR was assessed. The incidence of CR in different
      CD4+T lymphocyte count groups was analyzed. RESULTS: Among all participants, 58
      were male and 9 females, aged from 18-60 years, (38+/-9) years on average. CD4+ T
      lymphocyte count of CR patients ranged from 0-141 cells/ul and < 50 cells/ul in
      81.3% of cases. CR was the primary manifestation in 10.2%, retinal lesions in
      25.1%, best corrected visual acuity (BCVA) < 0.3 in 54% of AIDS patients. Retinal
      necrosis was involved near the posterior pole in 62.5% of CR patients. The visual
      acuity of 60 (47.6%) eyes was improved after treatment and 94.1% cases were cured
      within 3 months. Anti-CMV treatments including induction and maintenance of
      ganciclovir or foscarnet were discontinued when CD4+T lymphocyte count was > 150
      cells/ul for three consecutive months. Complicated cataract, retinal detachment
      and immune reconstitution uveitis were observed in 20.5%, 12.1% and 13.1% of
      cases, respectively. CONCLUSION: Decreased CD4+T lymphocyte count is a risk
      factor for CR. HAART and anti-CMV therapy are efficacious treatment of CR.
      Conventional eye examinations should be conducted to early diagnose CR or other
      opportunistic infections in all AIDS patients.

PMID- 26309621
TI  - Relationship between ADH2 Arg47His variation and hepatocellular carcinoma
      susceptibility: a meta analysis.
AB  - BACKGROUND: To further investigate the relationship between ADH2 Arg47His
      variation and hepatocellular carcinoma (HCC) susceptibility through a meta
      analysis. METHODS: The related articles were searched in PubMed, Embase and CNKI
      databases. And finally 518 cases and 607 controls were included in our meta
      analysis Odds ratios (ORs) with 95% confidence intervals (95% CIs) were used to
      assess the relationship between ADH2 Arg47His variation and HCC risk. A fixed
      effect model or a random-effect model was applied according to the between-study
      heterogeneity. RESULTS: Quantitative synthesis demonstrated that no significant
      association was found between ADH2 Arg47His variation and HCC susceptibility
      (His/His vs. Arg/Arg: OR=0.99, 95% CI=0.79-1.25; His/His + Arg/His vs. Arg/Arg:
      OR=1.01, 95% CI=0.86-1.20; His/His vs. Arg/Arg + Arg/His: OR=0.90, 95% CI=0.74
      1.11; His vs. Arg: OR=0.98, 95% CI=0.86-1.11; Arg/His vs. Arg/Arg: OR=1.05, 95%
      CI=0.82-1.34). CONCLUSION: Our analysis showed that ADH2 Arg47His vvariation may
      not be associated with HCC susceptibility.

PMID- 26309622
TI  - Serum levels of vascular endothelial growth factor and cancer antigen 125 are
      related to the prognosis of adenomyosis patients after interventional therapy.
AB  - AIMS: This study is to investigate the expression levels of vascular endothelial
      growth factor (VEGF) and cancer antigen 125 (CA125) in serum of adenomyosis
      patients before and after interventional therapy. The role of serum levels of
      VEGF and CA125 for the prognosis of adenomyosis is further studied. METHODS: A
      total of 80 adenomyosis patients treated with interventional therapy and 40
      healthy individuals were enrolled in this study. Enzyme-linked immunosorbent
      assay was performed to detect the expression levels of VEGF and CA125. Receiver
      operating characteristic analysis was used to determine the treatment effect on
      adenomyosis. Kaplan-Meier analysis was used to analysis the progression-free
      survival curve for prognosis of adenomyosis. RESULTS: The expression levels of
      VEGF and CA125 in serum of patients with adenomyosis was increased when compared
      with those of healthy individuals before interventional therapy (P < 0.05).
      Levels of hemoglobin in adenomyosis patients after surgery was increased compared
      with those before surgery (P < 0.05). The blood volume of menstruation, pain
      intensity, and volume of uterus in adenomyosis patients after surgery was
      significantly decreased when compared with those before surgery (P < 0.01). The
      survival rate of adenomyosis patients with high VEGF and CA125 levels was
      decreased. Serum levels of VEGF and CA125 had a high sensitivity and specificity
      for the prognosis of adenomyosis. CONCLUSIONS: The serum expression levels of
      VEGF and CA125 are related to the development of adenomyosis. VEGF and CA125
      serum levels can be used for predicting the prognosis of adenomyosis.

PMID- 26309623
TI  - Anaesthetic management of laparoscopic surgery for rectal cancer in patients of
      dilated cardiomyopathy with poor ejection fraction: a case report.
AB  - A patient with dilated cardiomyopathy with poor ejection fraction posted for
      laparoscopic surgery for rectal cancer which was successfully performed under
      general anesthesia with endotracheal intubation and mechanical ventilation was
      reported. Our observations strongly indicate that detailed preoperative
      assessment, watchful intraoperative monitoring, and skillful optimization of
      fluid status and hemodynamic play important role in the high risk patient under
      general anesthesia with endotracheal intubation and mechanical ventilation. 

PMID- 26309624
TI  - The decreased expression of miR-625 predicts poor prognosis of esophageal
      squamous cell carcinoma.
AB  - BACKGROUND: Previous study has detected the expression of miR-625 in esophageal
      squamous cell carcinoma (ESCC) and found that miR-625 was related to tumor depth,
      stage, and metastasis of ESCC. However, the prognostic value of miR-625 in ESCC
      has not yet been reported. METHODS: Real-time quantitative PCR was employed to
      measure the expression level of miR-625 in clinical ESCC tissues. Survival curves
      were made using the Kaplan-Meier method, and the log rank test was used to
      analyze the differences between clinicopathological characteristics and survival
      in ESCC patients. RESULTS: The expression level of miR-625 in ESCC tissues was
      significantly lower than that in adjacent non-tumor tissues (1.00 +/- 0.38 vs.
      3.25 +/- 1.83, P < 0.0001). Low miR-625 expression was observed to be closely
      correlated with lymph node metastasis (P = 0.01), distant metastasis (P = 0.007),
      tumor differentiation (P = 0.04), and advanced TNM stage (P = 0.005). The 5-year
      overall survival rate in the low expression group was 38.1%, compared with 68.8%
      in the high expression group (log-rank test, P = 0.001). Multivariate Cox
      regression analysis showed that miR-625 expression level (HR = 3.72, 95% CI: 1.36
      8.78, P = 0.005) was an independent factor in predicting the overall survival of
      ESCC patients. CONCLUSION: Our findings provide the convincing evidence for the
      first time that the down-regulation of miR-625 may serve as a novel molecular
      marker to predict the aggressive tumor progression and unfavorable prognosis of
      ESCC patients.

PMID- 26309625
TI  - One stage laminoplasty and posterior herniotomy for the treatment of myelopathy
      caused by cervical stenosis with cervical disc herniation.
AB  - The aim of the study was to introduce a method of one stage laminoplasty and
      posterior herniotomy for myelopathy caused by cervical stenosis with cervical
      disc herniation and to evaluate the clinical efficacy of this surgery. From 1999
      to 2008, 18 patients with myelopathy caused by cervical stenosis with cervical
      disc herniation who underwent this procedure were included. The average age was
      63 years (range 48-74 years), and the average follow-up period was 46 months
      (range 3-108 months). Neurologic status was evaluated using the JOA scoring
      system. Neurological symptoms improvement was seen in all patients after surgery.
      The average JOA score was 14.22+/-1.86 by final follow-up, which was higher than
      preoperative values (P<0.01), and the average improvement in neurological
      function was 76.63%. Neurologic examination showed that excellent results had
      been obtained by 10 patients, good results by 8 patients, with no fair or poor
      results. 2 patients developed cerebrospinal fluid leakage after surgery and
      recovered during the follow-up period. One patient with cervical disc herniation
      developed postoperative C5 palsy on the axle side on the third day after surgery.
      She completely recovered by 1 month after surgery. No other patients experienced
      postoperative neurologic complications. Complete anterior and posterior
      decompression of the spinal cord was achieved after surgery. We concluded that
      one stage laminoplasty and posterior herniotomy is an effective, reliable, and
      safe procedure for the treatment of myelopathy caused by cervical stenosis with
      cervical disc herniation. 

PMID- 26309626
TI  - Meta-analysis of macrophage migration inhibitory factor (MIF) gene -173G/C
      polymorphism and inflammatory bowel disease (IBD) risk.
AB  - Macrophage migration inhibitory factor (MIF) is a multi-functional cytokine
      associated with inflammation and inflammatory bowel disease (IBD). The
      association between MIF-173G/C polymorphism and IBD risk has been extensively
      investigated. However, the results were conflicted and inconclusive. Therefore,
      we performed this meta-analysis. Online electronic databases (PubMed and EMBASE)
      was searched. All statistical tests were performed with the software STATA
      version 11.0 (Stata Corporation, College station, TX, USA). A total of nine
      studies (ten cohorts) with 3436 cases and 2742 controls were included for this
      meta-analysis. MIF-173G/C polymorphism was associated with a significantly
      increased risk of IBD when compared with CG and GG genotypes (OR=1.43; 95% CI
      1.08-1.90; I(2) =0%). In the subgroup analysis according to ethnicity,
      significantly increased IBD risk was observed in Asians (OR=1.74; 95% CI 1.10
      2.74; I(2) =0%) but not in Caucasians (OR=1.27; 95% CI 0.89-1.82; I(2) =0%). In
      the subgroup analysis according to IBD type, significantly increased UC risk was
      observed (OR=1.43; 95% CI 1.04-1.95; I(2) =0%). In conclusion, this meta-analysis
      suggested that MIF-173G/C polymorphism was associated with increased IBD risk. 

PMID- 26309627
TI  - Lipoprotein lipase gene Hind III polymorphism was associated with hemorrhagic
      stroke.
AB  - OBJECTIVE: To investigate the relevance between lipoprotein lipase (LPL) Hind III
      gene polymorphism and cerebral hemorrhage. METHODS: A case-control study was
      performed utilizing PCR-RFLP method and sequencing of amplified products to
      detect LPL Hind III gene polymorphism in 350 cases of hemorrhagic stroke (HS
      group) and 350 healthy subjects (control group). Blood lipids and glucose levels
      were also recorded for each attendant. RESULTS: In HS group, T and G allele
      frequencies were 90.8% and 9.2%, respectively; while those in the control group
      were 82.3% and 17.7%. In HS group, detection rate of the G allele frequency and
      GG genotype were significantly lower than those in the control group. In
      addition, TG, LDL-C, fasting blood glucose , systolic blood pressure , diastolic
      blood pressure were significantly higher in HS group (P<0.05, P<0.01). Compared
      with TG+GG genotype, TT genotype population show significantly higher
      triglycerides concentration (P<0.05). With adjustment for hypertension, high
      blood sugar, and age -related factors, multivariate logistic regression analysis
      showed that LPL Hind III G allele could be a protective factor (OR = 0.392, 95%
      CI: 0.191~0.805, P = 0.011). CONCLUSION: LPL Hind III gene polymorphism was
      relevant to hemorrhagic stroke. LPL Hind III G mutant allele could be a
      protective factor in the pathogenesis of cerebral hemorrhage.

PMID- 26309628
TI  - Curcumin inhibits proliferation of interleukin-22-treated HaCaT cells.
AB  - The interleukin (IL)-23/IL-17A/IL-22 cytokine axis plays a critical role in the
      pathogenesis of psoriasis, wherein IL-22 effects on epidermal alternations by
      inhibiting differentiation and inducing keratinocyte proliferation. In this
      study, we investigated effects of curcumin on IL-22-induced proliferation in a
      human keratinocyte cell line (HaCaT) in vitro experiment. The HaCaT cells growth
      was measured by a Cell Counting Kit-8. The cyclin D1 and cyclin E was detected by
      real-time RT-PCR and weatern blot. The STAT3 and phosphorylation of STAT3 was
      tested by weatern blot also. Our results show that curcumin exhibited a
      significant anti-proliferation effect on HaCaT cells, even in the presence of IL
      22. Since STAT3 is crucial for IL-22 signal transduction, we examined the level
      of phosphorylation of STAT3 in all of the experimental groups. As expected,
      curcumin inhibited IL-22 induced phosphorylation of STAT3; furthermore, curcumin
      down regulated cyclin D1 and cyclin E. We can reach a conclusion that curcumin
      can suppress the proliferation of keratinocytes even with IL-22 treatment.
      Therefore, we have confidence in future curcumin research about psoriasis
      treatment. 

PMID- 26309629
TI  - Genetic sequencing analysis of the A307 subgroup of ABO blood group.
AB  - The aim of this study was to investigate the serology and gene sequence
      characteristics of the A307 subgroup of ABO blood group. Monoclonal anti-A and
      anti-B antibodies were used to detect the ABO antigens of a proband whose
      positive blood type was not consistent with the negative blood type of ABO blood
      group. Meanwhile, standard A-, B-, and O-negative typing cells were used to test
      for ABO antibodies in the serum. Additionally, polymerase chain reaction with
      sequence-specific primer (PCR-SSP) was used to confirm the genotype, and
      subsequently, exons 6 and 7 of the ABO gene were detected by gene sequencing.
      Samples from the wife and daughters of the proband were also used for serological
      and genetic testing. Red blood cells of the proband showed weak agglutination
      reaction with anti-A antibody, while anti-B antibody was detected in the serum.
      Moreover, PCR-SSP detected A307 and O02 alleles, while gene sequencing revealed
      mutation of c.745C>T in exon 7, which produced a polypeptide chain p.R249W.
      Furthermore, the A307 gene of the proband was not inherited by his daughters. A
      mutation (c.745 C>T) in exon 7 of the ABO blood group gene resulted in low
      activity of alpha-1, 3-N-acetyl-galactosaminyl transferase, producing A3
      phenotype. 

PMID- 26309630
TI  - The positive therapeutic effect in a patient of Evans syndrome combined with
      acute myocardial infarction.
AB  - Evans syndrome (ES) is a rare combination of autoimmune hemolytic anemia and
      thrombocytopenia. This case report details an old male ES patient with acute
      myocardial infarction. He was successfully treated by primary percutaneous
      coronary intervention in the case of low hemoglobin level (60 g/L). Considering
      ES recurrence after surgery, he was given human immunoglobulin, methyl
      prednisolone and TPO treatment. On the basis of his platelet count, the patient
      was required to take only one anti-platelet drug or stop all anti-platelet drugs.
      To the best of our knowledge, this is the first report of ES with AMI. This case
      suggests that primary PCI can be a useful therapeutic strategy even if patient
      has low hemoglobin level, but careful balance between anti-platelet therapy and
      efforts to raise platelet count are needed after surgery. 

PMID- 26309631
TI  - Pemetrexed induced a durable response in heavily pretreated metastatic
      extramammary Paget's disease.
AB  - PURPOSE: Extramammary Paget's disease (EMPD) is a rare neoplasm with only a
      limited number of cases reported in the literature. Little was known about the
      availability of systemic chemotherapy for metastatic EMPD. METHODS: We report one
      case of heavily pretreated EMPD with multiple organ metastases and successfully
      treated by pemetrexed. RESULT: The tumor was progression after multi-line therapy
      including erlotinib, radiotherapy, combined chemotherapy and radioactive
      particles implantation. Pemetrexed monotherapy was applied and progression free
      survival of more than 5 months with partial remission (PR) response was achieved.
      Only 1 time of grade 3 neutropenia was observed during the pemetrexed
      chemotherapy. CONCLUSION: Due to the significant response and tolerability in the
      present case, pemetrexed monotherapy was recommended as a potent candidate for
      patients with advanced EMPD.

PMID- 26309632
TI  - Effect of interleukin-6 polymorphism on fracture risk.
AB  - BACKGROUND: Interleukin-6 (IL6) -174C/G polymorphism was suggested to be
      associated with fracture risk. However, the results were inconsistent. Thus, we
      did a meta-analysis. METHODS: Reported studies were searched from online
      electronic databases of Pubmed, EMBASE, Chinese National Knowledge Infrastructure
      (CNKI). The odds ratios (ORs) and corresponding 95% confidence intervals (CIs)
      were calculated to assess the association between IL6 -174C/G polymorphism and
      fracture risk. RESULTS: Six studies evaluated the association between IL6 -174C/G
      polymorphism and fracture risk. A significant association was found between IL6 
      174C/G polymorphism and fracture risk (OR=1.25; 95% CI, 1.10-1.43; P=0.0008). In
      the subgroup analysis of gender, we found that women with IL6 -174C/G
      polymorphism had an increased fracture risk (OR=1.25; 95% CI, 1.07-1.46;
      P=0.005). In the subgroup analysis of type of fracture, we found that IL6 -174C/G
      polymorphism was significantly associated with wrist fracture (OR=1.25; 95% CI,
      1.07-1.47; P=0.006) and osteoporotic fracture (OR=1.60; 95% CI, 1.12-2.28;
      P=0.009). However, no significant association was found between IL6 -174C/G
      polymorphism and hip fracture (OR=1.05; 95% CI, 0.89-1.24; P=0.53) and stress
      fracture (OR=1.25; 95% CI, 0.97-1.61; P=0.08). CONCLUSION: This meta-analysis
      suggested that the IL6 -174C/G polymorphism was associated with wrist and
      osteoporotic fracture risk.

PMID- 26309633
TI  - Relative potency ratio between hyperbaric and isobaric solutions of ropivacaine
      in subarachnoid block for knee arthroscopy.
AB  - OBJECTIVE: To observe the potency ratio of hyperbaric to isobaric solutions of
      ropivacaine in subarachnoid block for knee arthroscopy. METHODS: Fifty patients
      receiving knee arthroscopy under combined spinal-epidural anesthesia were
      randomly divided into isobaric ropivacaine group and hyperbaric ropivacaine group
      (0.5% ropivacaine, prepared with equal volume of 10% glucose and 1% isobaric
      ropivacaine). Successful criteria of spinal anesthesia were (1) a bilateral loss
      of pinprick sensation at or above the level of T12; (2) adequate motor block
      during knee arthroscopy (modified Bromage's score >=2); and (3) no requirement of
      additional epidural administration at least within 60 min after intrathecal
      injection. Drug consumption was determined with up-and-down method, and then ED50
      was calculated. RESULTS: The ED50 of isobaric ropivacaine was 9.71 mg (95% CI
      8.11-11.32), and the ED50 of hyperbaric ropivacaine was 6.55 mg (95% CI 6.07
      7.04), and the relative potency ratio was 0.67 (95% CI 0.56-0.80) for
      hyperbaric/isobaric ropivacaine. CONCLUSIONS: The ED50 of hyperbaric ropivacaine
      is less than that of isobaric ropivacaine in subarachnoid block anesthesia for
      knee arthroscopy.

PMID- 26309634
TI  - Hepatic sarcoidosis mimicking liver cancer.
AB  - We present a case of a 50-year-old woman with multiple occupations in the liver.
      Liver cancer was strongly suspected initially according to the results of imaging
      examination. However, sarcoidosis was confirmed subsequently by liver biopsy, so
      methylprednisolone was then prescribed and the patient showed favorable
      therapeutic response. This case report suggests that hepatic mass in Chinese
      patients without any history of hepatitis virus infection should be carefully
      investigated before giving a diagnosis of liver cancer. The report also reminds
      us that the clinical presentation of sarcoidosis is complex and involvement of a
      single extra-pulmonary organ should not be ignored. 

PMID- 26309635
TI  - Reduced self-regulation of cerebrum contributes to executive impairment in
      patients with temporal lobe epilepsy.
AB  - The aim of this study was to investigate the role of self-regulation of cerebrum
      in the executive impairment. 22 subjects were enrolled were assessed by a
      neuropsychological test of executive function using attentional networks test and
      the cerebral activity was evaluated by functional magnetic resonance imaging. The
      patients with TLE had a longer reaction time than controls (P < 0.05). Moreover,
      the healthy controls showed more right hemisphere lateralized activation in
      incongruent tasks. Finally, both positively and negatively correlated cerebral
      areas were found in the healthy controls but only negatively correlated cerebral
      areas were found in the TLE patients. Reduced cerebral lead to areas and lack of
      activation of right midline positively self-regulatory cerebral areas may
      executive impairment in TLE patients. 

PMID- 26309636
TI  - Biomechanic effect of posterior cruciate ligament rupture on lateral meniscus.
AB  - OBJECTIVE: This study aims to investigate the biomechanical effect of posterior
      cruciate ligament (PCL) rupture on lateral meniscus. METHOD: The stresses of
      anterior horn, caudomedial part and posterior horn of lateral meniscus in
      cadaveric knees were recorded when the knee joints were loaded 200 to 1000 N at
      0, 30, 60 and 90 degrees  of flexion. Twelve knees were tested before PCL
      transection (intact group), and 6 each were then tested after anterolateral
      bundle (ALB group) and postmedial bundle (PMB group) transection. The same knees
      were finally tested after complete PCL transection. RESULT: At 0 degrees of knee
      flexion, the stresses of the anterior horn, caudomedial part and posterior horn
      were negative and compressive, and were not significantly different between
      intact and ALB groups, and between completely transected and PMB groups at 200
      and 400 N. The stresses of the anterior horn and caudomedial part were greater in
      completely transected and PMB groups than in intact and ALB groups. The stresses
      of the posterior horn were smaller in PMB and completely transected groups than
      in intact and ALB groups. At 600-1000 N, the stresses were significantly
      different between the groups. The absolute stresses of the anterior horn and
      caudomedial part were in order of completely transected > PMB > ALB > intact
      group, while these of the posterior horn were reversed. At 30 degrees  of knee
      flexion, the stresses of the three parts were not significantly different between
      intact and PMB groups nor between completely transected and ALB groups at 200 and
      400 N. The stresses in the anterior horn and caudomedial part were negative and
      different between completely transected and ALB groups, and positive and
      different between intact and PMB groups. The stresses in the posterior horn were
      positive and different between completely transected and ALB groups, and negative
      and different between intact and PMB groups. At loads of > 600 N, the stresses in
      the anterior horn and caudomedial part were negative in completely transected and
      ALB groups, and positive in intact and PMB groups. The stresses of the posterior
      horn were positive in completely transected and ALB groups and negative in intact
      and PMB groups, with significant difference between the groups. At 60 degrees 
      and 90 degrees  of flexion, the stresses of the anterior horn and caudomedial
      part were positive in completely transected and ALB groups and positive in intact
      and PMB groups, while the stresses of posterior horn were in the opposite
      directions and were significantly different between the groups at the same loads.
      CONCLUSION: Complete transection of PCL will result in stress changes in various
      parts of lateral meniscus. At 200 and 400 N, transection of ALB and PMB do not
      change the stress at 0 degrees  and 30 degrees  of flexion, respectively. At
      heavier loads (600-1000 N), the stresses at these angels are affected in ALB and
      PMB groups. At all loaded tested, transection of ALB and PMB results in changed
      stresses in all regions of lateral meniscus at 30-90 degrees  and 0-90 degrees 
      of flexion, respectively.

PMID- 26309637
TI  - Detection and analysis of resistance mutations of hepatitis B virus.
AB  - OBJECTIVE: To investigate the relationships of resistance mutations of hepatitis
      B virus (HBV) with replication and genotypes of HBV and to understand the common
      resistance mutations and mutation pattern. METHODS: The mutation patterns related
      to resistance to nucleoside drugs were analyzed, and the relationships of
      resistance mutations with HBV genotypes, Ct value, HBeAg, alanine
      aminotransferase (ALT), age and gender were evaluated. RESULTS: Genotype B was
      found in 52 patients (73.2%) and genotype C in 19 patients (26.8%). In addition,
      32 patients (45.07%) had resistance mutations at different loci, of which single
      base mutation accounted for 56.25% (18/32) and multi-base mutation for 43.75%
      (14/32). Of single base mutation, L180M, M204I, M204V and V173L had higher
      prevalence, and the incidence of L180M was closely related to the genotype of
      HBV. L180M, M204I and M204V were associated with the resistance to lamivudine and
      telbivudine; L180M, M204I, M204V and V173L were associated with the resistance to
      entecavir; A181T, N236T and N/H238T were related to the resistance to adefovir.
      Of multi-base mutations, L180M combined M204V had a high prevalence and were
      frequently found in patients with resistance to lamivudine and telbivudine. There
      was cross-resistance between lamivudine and telbivudine, between lamivudine and
      entecavir, and between entecavir and telbivudine. The Ct value of HBV DNA, HBeAg,
      ALT, age and gender were comparable among patients with different resistance
      mutations and HBV genotypes. CONCLUSION: Detection of mutations of multiloci
      resistance genes is helpful for timely identification of HBV resistance and the
      clinical anti-virus therapy.

PMID- 26309638
TI  - Potential role for carbon nanoparticles identification and preservation in situ
      of parathyroid glands during total thyroidectomy and central compartment node
      dissection.
AB  - OBJECTIVE: To determine the potential role of intraoperative carbon nanoparticles
      (CN) injections for identification and preservation of parathyroid glands,
      thereby reducing the postoperative hypocalcaemia. METHODS: 100 patients with
      thyroid cancer who underwent total thyroidectomy and central compartment node
      dissection (CCND) were randomly assigned to receive intraoperative injection of
      (CN) or not for identifying and preserving normal parathyroid glands. RESULTS:
      There was no significantly difference for preoperative and postoperative
      parathyroid hormone (PTH) levels between the CN and control group (P>0.05). The
      levels of albumin-adjusted serum calcium (AASC) before surgery and at day 1 and 1
      month after surgery did not reach the significant difference between the two
      groups (P>0.05). However, the patients in CN group had the higher level of AASC
      at day 3 after surgery than those in control group (P=0.044). Transient
      postoperative hypoparathyroidism occurred in 24 (48%) patients in CN group and 28
      (56%) in control groups, respectively (P=0.423). The incidence of transient
      postoperative hypocalcemia was 20% (10/50) in CN group and 24% (12/50) in control
      groups, respectively (P=0.629). CONCLUSIONS: Carbon nanoparticles can make the
      thyroid gland and the central lymph node black-stained, but no-stained for
      parathyroid glands. After rapidly identifying parathyroid and distinguishing it
      from thyroid and lymph nodes by carbon nanoparticles, complete lymph node
      dissection and preservation of parathyroid glands become feasible during total
      thyroidectomy with neck lymph node dissection. After identification, strict
      adherence to capsular dissection remains essential for safe preservation in situ
      of the parathyroid glands and their blood supply.

PMID- 26309639
TI  - The association and interaction analysis of metabolic syndrome and chronic kidney
      disease on cardiovascular autonomic neuropathy in the general Chinese population.
AB  - BACKGROUND: The objective of this study was to evaluate associations of metabolic
      syndrome (MetS) and chronic kidney disease (CKD) with cardiovascular autonomic
      neuropathy (CAN), and to estimate the extent to which interaction of MetS and CKD
      affects the outcome in the Chinese population. METHOD: We conducted a large
      scale, population-based study to analyze the association and interaction of the
      two factors for CAN in a sample of 2,092 Chinese people. Univariate and multiple
      linear regression (MLR) analysis were employed to detect these relationships.
      Interaction on an additive scale can be calculated by using the relative excess
      risk due to interaction (RERI), the proportion attributable to interaction (AP),
      and the synergy index (S). RESULTS: MLR adjusted for confounding factors showed
      that MetS was independently associated with CAN (P < 0.001). A significant
      interaction effect was detected by MLR (P = 0.042). In addition, a positive
      interaction between MetS and CKD on CAN was estimated by using parameters of RETI
      = 0.119 (95% CI: 0.059-0.178), AP = 0.049 (95% CI: -0.039-0.138) and S = 1.091
      (95% CI: 0.164-2.019). CONCLUSION: Our findings suggest that MetS is
      independently associated with CAN and offer evidence to support the hypothesis
      that MetS and CKD have positive interactions on CAN.

PMID- 26309640
TI  - Results of multimodal treatment for desmoplastic small round cell tumor of the
      abdomen and pelvis.
AB  - PURPOSE: Desmoplastic small round cell tumor (DSRCT) is a rare aggressive
      malignancy that occurs in a young population with a male predominance. We studied
      the clinical and pathological characteristics of DSRCT and investigated the
      effects of multimodal therapy including aggressive surgical resection, induction
      chemotherapy, and external beam radiotherapy. METHODS: We retrospectively
      reviewed and analyzed our experience with 11 histologically proven cases of DSRCT
      between March 2004 and October 2014. The clinical information, histological,
      immunohistochemistry and survival data of the patients were collected. RESULTS:
      The median age at diagnosis was 31.4 years (range, 14-64 years) and nine (82%) of
      the patients were males. The most common presenting complaint was abdominal pain
      (72.7%). Surgical resection was attempted in five patients and included
      macroscopic total resection in two patients and debulking in three patients. Six
      patients underwent biopsy only. Eleven patients received multiagent chemotherapy.
      Five patients (45.5%) received radiotherapy. The median survival of patients who
      underwent surgical resection was 34.5 months, whereas the patients who underwent
      biopsy alone was 24.5 months (P<0.05). The median survival was 40.8 months in
      radiotherapy group, and 19.2 months in non-radiotherapy group (P<0.05). The 3
      year progression-free survival rate was 27.2%. The median survival was 29 months,
      and the median time to local failure was 8.8 months. Cox regression analysis
      showed surgery and radiotherapy were highly significant in prolonging patients
      survival. CONCLUSION: Multimodal therapy consists of combination of surgical
      resection, chemotherapy and radiotherapy results in improved survival in patients
      with DSRCT. For unresectable DSRCT, we recommend radiotherapy combined with
      anthracycline-based chemotherapy.

PMID- 26309641
TI  - Prenatal emotion management improves obstetric outcomes: a randomized control
      study.
AB  - INTRODUCTION: Negative emotions can cause a number of prenatal problems and
      disturb obstetric outcomes. We determined the effectiveness of prenatal emotional
      management on obstetric outcomes in nulliparas. METHODS: All participants
      completed the PHQ-9 at the baseline assessment. Then, the participants were
      randomly assigned to the emotional management (EM) and usual care (UC) groups.
      The baseline evaluation began at 31 weeks gestation and the participants were
      followed up to 42 days postpartum. Each subject in the EM group received an extra
      EM program while the participants in the UC groups received routine prenatal care
      and education only. The PHQ-9 and Edinburgh Postnatal Depression scale (EPDS)
      were used for assessment. RESULTS: The EM group had a lower PHQ-9 score at 36
      weeks gestation, and 7 and 42 days after delivery (P < 0.01), and a lower EPDS
      score 42 days postpartum (P < 0.05). The rate of cesarean section in the EM group
      was lower than the UC group (P < 0.01), and the cesarean section rate without a
      medical indication was lower (P < 0.01). The duration of the second stage of
      labor in the EM group was shorter than the UC group (P < 0.01). CONCLUSIONS:
      Prenatal EM intervention could control anxiety and depressive feelings in
      nulliparas, and improve obstetric outcomes. It may serve as an innovative
      approach to reduce the cesarean section rate in China.

PMID- 26309642
TI  - Analysis of prognostic factors in lymphoma patients with bone marrow involvement:
      a single center cohort study.
AB  - The objective of this study was to explore prognostic factors in lymphoma
      patients with bone marrow involvement (Ann Arbor stage IV). To that end, we
      analyzed a cohort study of 68 stage IV lymphoma patients. We found that the most
      predictive thresholds for lymphocyte rate, monocyte rate, and lymphocyte to
      monocyte ratio (LMR) were 30%, 13%, and 3, respectively. A lymphocyte rate <30%,
      a monocyte rate >13%, and the presence of B symptoms were associated with shorter
      OS. LMR >3, Eastern Oncology Cooperative Group performance status <=1, indolent
      lymphoma, and B cell (as opposed to T and NK cell) lymphoma predicted longer OS.
      Our study showed that these basic, easily acquired data can predict the outcome
      and overall survival in lymphoma patients with bone marrow involvement. These
      prognostic markers should be taken into consideration when devising new
      prognostic scoring systems for lymphomas. 

PMID- 26309643
TI  - The importance of the mesh shape in preventing recurrence after Nissen
      fundoplication.
AB  - Gastro esophageal reflux disease (GERD) is the most common gastrointestinal
      disorder and often is associated with hiatal hernia (HH). Nissen fundoplication
      is the most common surgical treatment method. Despite surgical treatment,
      recurrence rate is still high. In this study, we aimed to identify the importance
      of the mesh shape in preventing recurrence after Nissen fundoplication. A hundred
      twenty two patients who operated Nissen fundoplication owing to GERD and/or HH
      were evaluated. Nissen fundoplication was made all patients. Patients were
      divided into three groups according to hiatoplasty procedure; group 1 (V-shaped
      mesh), group 2 (V-shaped mesh + Fibrin glue), and group 3 (special designed mesh,
      Kar's mesh). Groups were compared regarding intraoperative, postoperative early-
      and long-term complications. Mean age was 42.75 years, and male to female ratio
      was 1:2.98. The mean follow-up period was 27 mounts. There was no mortality
      during follow-up. The most common presenting symptom was heartburn (93.4%). There
      wasn't difference between groups in terms of the intraoperative complications and
      postoperative early-term complications. The overall recurrences rate was 4.9% and
      dysphagia > 3 months rate was 1.6%. No recurrence was not observed in group 3,
      while recurrence was observed in 4 patients in group 1 (P = 0.030). Patients
      should be carefully selected for surgery because complication rate is high
      despite successful anti-reflux surgical treatment. In this study, we have used a
      special designed mesh. We believe that this special designed mesh can be used
      safely and effectively in anti-reflux surgery because recurrence and
      complications were not observed. 

PMID- 26309644
TI  - To decide medical therapy according to ECG criteria in patients with
      supraventricular tachycardia in emergency department: adenosine or diltiazem.
AB  - The aim of this study is to investigate the effect of ECG criteria which are used
      for the distinction between AVNRT and AVRT for the choice of treatment in
      patients with Supraventricular Tachycardia (SVT). The 77 patients with narrow QRS
      complex SVT which was treated with Adenosine or Diltiazem in the Emergency
      Department were evaluated retrospectively. All 12-lead ECG during tachycardia
      were blindly reviewed according to ECG criteria (Pseudo-r' in V1, Pseudo-S-wave
      in the inferior leads, Visible P-wave, aVL notch) by a cardiologist and an
      emergency physician. In this study, while 59.6% of the patients returned to
      normal sinus rhythm (NSR) after the first dose 6 mg, 64.91% of them after the
      first dose 12 mg and 71.92% of them after the second dose of 12 mg adenosine, 95%
      of the patients returned to NSR after the 0.25 mg/kg diltiazem. The most visible
      ECG findings were visible P waves and the least visible ECG findings were Pseudo
      S waves in the inferior leads. It was statistically significant between converted
      by adenosine to NSR and converted by diltiazem to NSR to the presence of visible
      P-wave and the aVL lead notch in their ECG findings. CONCLUSION: The rate of
      return to NSR through diltiazem was found higher than that of adenosine in narrow
      complex SVT patients. Also, diltiazem may be the first medication to be preferred
      in the presence of retrograt P wave and aVL notch in the ECG of the patients with
      narrow QRS complex stable SVT.

PMID- 26309645
TI  - Platelet abnormalities in chronic thromboembolic pulmonary hypertension.
AB  - The reasons for non-resolving thrombosis in chronic thromboembolic pulmonary
      hypertension (CTEPH) have not been fully elucidated. Despite platelets being
      implied in its pathogenesis, they have been poorly studied. We hypothesized that
      platelets would be altered in CTEPH. The aim of our study was to compare selected
      platelet parameters in CTEPH patients with healthy subjects. The study included
      healthy subjects (n = 50) and patients with CTEPH (n = 47). We investigated
      platelet count, mean platelet volume (MPV), and platelet aggregation-spontaneous
      (SPA) and induced by various concentrations of five agonists. In addition, some
      other hemostatic parameters were also investigated to provide a comprehensive
      view on hemostasis. We found a decreased platelet count [212 (171-251) versus 248
      (205-408) 10(9) L(-1), P<0.01], higher MPV [11.3 (10.5-11.7) versus 10.1 fL (9.4
      10.4), P<0.001] and higher SPA [9.5 (7.1-12.4) versus 5 (1.3-9) %, P<0.001], but
      a decrease of induced platelet aggregation (only by maximal agonist
      concentrations) in CTEPH patients compared to controls. These changes were
      accompanied by a significant increase of plasma fibrinogen, factor VIII, von
      Willebrand factor (antigen and activity), and plasminogen activator inhibitor.
      Thus, we can conclude that CTEPH is accompanied by a prothrombotic state,
      including platelet abnormalities. They reflect a higher platelet
      turnover/reactivity and specific platelet behavior (impaired aggregation) in
      these patients. Our findings imply that platelet disorders can contribute to the
      pathogenesis of CTEPH. However, further research would be desirable to better
      understand the reason for this finding. 

PMID- 26309646
TI  - Gender of patients and level of osteotomy are predictive factors for blood loss
      in ankylosing spondylitis patients undergoing pedicle subtraction osteotomy.
AB  - This study is to investigate the predictive factors of blood loss in ankylosing
      spondylitis (AS) patients. Retrospective analysis was performed in patients with
      thoracolumbar kyphotic deformity secondary to ankylosing spondylitis who
      underwent PSO from 2008 through 2013. Patient's demographics, preoperative and
      postsurgical global kyphosis (GK) angle, preoperative hematologic tests and other
      factors related to PSO were analyzed. Multiple regression analysis was used to
      determine the predictive factors of intraoperative blood loss. A total of 67 AS
      patients including 61 males and 6 females were included in the study. These had
      an average age of 33.97 years (17-55 years) and an average preoperative height of
      167.77 cm (124-182 cm). There were 55 patients undergoing one-level osteotomy and
      12 patients undergoing two-level osteotomy. Preoperative and postoperative GK
      angles were 79.08 degrees  +/- 24.11 degrees  and 35.68 degrees  +/- 21.48
      degrees , respectively. The mean surgical correction rate was 56.62% +/- 21.45%.
      The mean length of surgery was 404.25 +/- 82.57 minutes, and the estimated
      intraoperative blood loss was 2899.25 +/- 1444.54 ml. The average percentage of
      estimated blood loss (EBL)/estimated blood volume (EBV) was 69.98% +/- 41.44%
      (range, 23.57%-248.52%). Multiple stepwise analysis identified male sex (P =
      0.000), and two-level osteotomy (P = 0.016) to be predictive factors of increased
      EBL/EBV percentage in AS patients undergoing PSO for thoracolumbar kyphosis. Male
      and two-level osteotomy are the two most significant factors predicting increased
      EBL/EBV percentage in AS patients undergoing PSO for thoracolumbar kyphosis.
      These predictors can provide more adequate preoperative preparations. 

PMID- 26309647
TI  - Effect of ademetionine on cytochrome P450 isoforms activity in rats.
AB  - Cocktail method was used to evaluate the influence of ademetionine on the
      activities of CYP450 isoforms CYP1A2, CYP2D6, CYP3A4, CYP2C19, CYP2C9 and CYP2B6,
      which were reflected by the changes of pharmacokinetic parameters of six specific
      probe drugs phenacetin, metroprolol, midazolam, omeprazole, tolbutamide and
      bupropion, respectively. The experimental rats were randomly divided into two
      group, control group and ademetionine group. The ademetionine group rats were
      given 50 mg/kg ademetionine by continuous oral administration for 7 days. The
      mixture of six probes was given to rats through oral administration and the blood
      samples were obtained at a series of time-points through the caudal vein. The
      concentrations of probe drugs in rat plasma were measured by UPLC-MS/MS. In the
      experiment for ademetionine and control group, there was statistical
      pharmacokinetics difference for phenacetin, metroprolol, midazolam, omeprazole,
      tolbutamide and bupropion. Continuous oral administration for 7 days could induce
      the activities of CYP450 isoforms CYP1A2 of rats, while it may inhibit the
      activities of CYP2D6, CYP3A4, CYP2C19 and CYP2C9. 

PMID- 26309648
TI  - Prognosis of ultra-early microsurgery combined with extraventricular drainage in
      patients with poor-grade aneurysms.
AB  - OBJECTIVE: To explore the clinical effects of ultra-early microsurgery (< 24
      hours) combined with extraventricular drainage for the treatment of poor-grade
      aneurysms. METHODS: A total of 60 patients with poor-grade aneurysms were
      randomly divided into a microsurgery combined with extraventricular drainage
      (MED) group and conventional microsurgery (M) group. The prognosis was
      comparatively studied for these 2 groups. RESULTS: All patients underwent a
      Glasgow Outcome Scale (GOS) assessment during a 6-month to 2-year follow-up. The
      excellent recovery (GOS, 4-5 points) rate for the MED group was 30% higher than
      that of the M group, while the poor recovery (GOS, 1-2 points) rate was 26.7%
      lower than that of the M group (P = 0.016). The incidence of acute brain swelling
      (26.7% vs 53.3%; P = 0.035), cerebral infarction (20% vs 46.7%; P = 0.025), and
      vasospasm (16.7% vs 40%; P = 0.045) for the MED group was significantly lower
      than that of the M group. CONCLUSIONS: For microsurgery combined with
      extraventricular drainage, the risk of cerebral infarction and vasospasm were
      significantly reduced for patients with poor-grade aneurysms, and the prognosis
      was better.

PMID- 26309649
TI  - Serum copeptin as a new biomarker in the early diagnosis of decline in renal
      function of type 2 diabetes mellitus patients.
AB  - OBJECTIVE: This study aimed to investigate the correlation between serum copeptin
      and glomerular filtration rate (GFR) in type 2 diabetes mellitus (T2DM) patients
      and to investigate the role of serum copeptin in the diagnosis of early DN in
      T2DM patients. METHODS: 120 T2DM inpatients were recruited and divided into 2
      groups according to 24-h urine albumin excretion (UAE): normal UAE group (UAE<30
      mg/24 h) and microalbuminuria group (30 mg/24 h<=UAE<=300 mg/24 h). RESULTS:
      Decline in GFR was found in 6.1% of patients in normal UAE group and 26.4% in
      microalbuminuria group. However, serum copeptin was comparable between two
      groups. Serum copeptin was negatively related to GFR (r=-0.586, P<0.001).
      Multivariate logistic regression analysis showed, after adjustment for age and
      gender, the OR of copeptin, 24-h UAE was 1.234 (95% CI: 1.003-1.456) (P<0.05) and
      1.068 (95% CI: 1.005-1.187) (P<0.05), respectively. Univariate analysis of ROC
      showed the sensitivity of copeptin and 24-h UAE was 78.9% and 63.2%, respectively
      and the specificity was 88.9% and 89.7%, respectively in the diagnosis of DN, but
      the area under ROC of copeptin in combination with 24-h UAE was 0.90 (95% CI:
      0.82-0.99) with the sensitivity of 80.9% and specificity of 91.1%. CONCLUSION:
      Serum copeptin is an independent risk factor of decline in renal function of T2DM
      patients. Copeptin in combination with 24-h UAE are helpful for the early
      diagnosis of DN. The causative relationship between serum copeptin and GFR is
      required to be further studied in long-term follow up.

PMID- 26309650
TI  - Effect of Radix Sophorae Tonkinensis on the activity of cytochrome P450 isoforms
      in rats.
AB  - Radix Sophorae Tonkinensis (S. tonkinensis) is the processed lateral root of
      Sophora subprostrata (Leguminosae) that widely distributed over the southwest
      China. Radix Sophorae Tonkinensis has been widely used as a Chinese medicinal
      herb for the treatment of disease such as jaundice, inflammation, and aches.
      Herein, in order to investigate the effects of Radix Sophorae Tonkinensis on the
      metabolic capacity of rat cytochrome P450 (CYP) enzymes, we employed a cocktail
      method to evaluate the activities of CYP1A2, CYP2D6, CYP3A4, CYP2C19, CYP2C9 and
      CYP2B6. The experimental rats were randomly divided into two groups (control
      group and Radix Sophorae Tonkinensis treated group). The Radix Sophorae
      Tonkinensis treated group rats were given 5 g/kg Radix Sophorae Tonkinensis by
      continuous intragastric administration for 14 days. The mixture of six probes
      (phenacetin, metroprolol, midazolam, omeprazole, tolbutamide and bupropion) was
      given to rats by intragastric administration. The concentrations of probe drugs
      in rat plasma were measured by UPLC-MS/MS. The results showed that continuous
      intragastric administration for 14 days may inhibit the activities of rat CYP450
      isoforms CYP2D6, CYP2C19 and CYP2B6. This finding may provide guidance for
      rational clinical uses of Radix Sophorae Tonkinensis. 

PMID- 26309651
TI  - Correlation between polymorphism of FTO gene and type 2 diabetes mellitus in
      Uygur people from northwest China.
AB  - BACKGROUND: To explore the correlation between FTO (fat mass and obesity
      associated) gene, which is associated with 3 single nucleotide polymorphisms
      (SNP) of fat mass and obesity, type 2 diabetes and body mass index (BMI) in the
      Uygur population in northwest China. METHODS: A total of 849 Uygur patients with
      type 2 diabetes mellitus were selected from the hospitalized patients in the
      First Affiliated Hospital of Xinjiang Medical University, the First People's
      Hospital of Kashi and the hospitals in the Turpan areas. At the same time, 873
      cases of healthy persons who conducted a medical checkup in the physical
      examination centre of the above hospitals were enrolled as controls. The present
      investigation used the case-control research method, and physical examination and
      biochemical index determination were carried out. The Sequenom MassARRAY
      technology was employed in the detection of 3 SNP loci of the FTO gene. The
      representative population of each SNP in the control group was analyzed by Hardy
      Weinberg law. The differences of each clinical parameter in the two groups were
      analyzed by t-test analysis. The differences of genotype and allele of each SNP
      in the two groups were analyzed by chi(2) test. RESULTS: BMI, waistline (WL),
      systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood
      glucose (FBG), total cholesterol (TC), aspartate aminotransferase (AST) and
      alanine aminotransferase (ALT) in the type 2 diabetes group were higher than
      those in the control group, while the high density lipoprotein (HDL) and low
      density lipoprotein (LDL) were lower than those of the control group; 2. The
      allele frequency of A of rs8050136 and rs9939609 in the type 2 diabetes mellitus
      group was higher than that of the control group. The BMI of the whole population
      and type 2 diabetes group with genotype C/A+A/A of rs8050136 was higher than that
      in C/C group, and the BMI with genotype T/A+A/A of rs9939609 was higher than that
      in group T/T. Stratification was conducted on BMI according to the normal,
      overweight and obesity criteria. There were significant differences in the
      distribution of genotype frequency of rs9939609 in the type 2 diabetes group and
      the control group of the normal BMI group. CONCLUSION: Single nucleotide mutation
      of rs7195539 in FTO gene may be a protective factor against the Uygur type 2
      diabetes. Single nucleotide mutations of rs8050136 and rs9939609 may be
      associated with the Uygur type 2 diabetes and obesity, with A as a potential risk
      allele. The gene polymorphism of rs8050136 may correlate with type 2 diabetes
      mellitus through the function of BMI, while the correlation between rs9939609
      gene polymorphism and type 2 diabetes is not depending from BMI.

PMID- 26309652
TI  - Treatment of middle-super thoracic fractures associated with the sternum
      fracture.
AB  - To analyze the characteristics and treatment of middle-super thoracic fractures
      associated with the sternum fracture, twenty six patients with middle-super
      thoracic fractures associated with the sternum fracture were retrospectively
      reviewed. The intimate information of patients including age, gender, cause of
      injury, site of the sternal fracture, level and type of thoracic vertebral
      fracture, spinal cord injury and associated injuries were included in the
      analysis. There were 12 compressed fractures, 11 fracture-dislocations, two burst
      fracture and one burst-dislocation in this study. Six patients had a complete
      lesion of the spinal cord, nine sustained a neurologically incomplete injury and
      11 were neurologically intact. Nine patients were treated non-operatively and 17
      were underwent surgery. All patients were followed up for 8~99 months. Our
      results showed that road traffic accidents (RTA) and fall were the dominated in
      the causes. All six patients with a complete paralytic lesion were not recovered
      with any significant function. Four out of eleven neurologically intact patients
      had local pain although ten of them remained normal function and one patient turn
      up tardive paralysis. One of nine patients with incomplete paraplegia returned to
      normal and four recovered with some function. These study suggested that the
      sternum is one of the important parts in constructing thoracic cage and plays an
      important role in maintain the stabilization of the thoracic vertebra. Because of
      the unique anatomy and biomechanics of the thoracic cage, the classification
      commonly applied to thoracic vertebra fractures is not suitable for middle-super
      thoracic fractures associated with the sternum fracture. Middle-super thoracic
      fractures associated with the sternum fracture was marked by violent force,
      severe fractures of spine, severe injuries of spinal cord and high incidence of
      associated injuries. These cases confirm the existence and clinical relevance of
      the fourth column of the thoracic spine and its role for spinal stability in the
      patient with middle-super thoracic fracture. 

PMID- 26309653
TI  - Proliferation PET image to characterize pathological spatial features in patients
      with non-small cell lung cancer: a pilot study.
AB  - PURPOSE: (18)F-FLT-PET imaging was proposed as a tool for measuring in vivo tumor
      cell proliferation and detecting sub-volumes to propose escalation in
      radiotherapy. The aim of this study was to validate whether high FLT uptake areas
      in (18)F-FLT PET/CT are coincident with tumor cell proliferation distribution
      indicated by Ki-67 staining in non-small cell lung cancer, thus provide
      theoretical support for the application of dose painting guided by (18)F-FLT
      PET/CT. MATERIALS AND METHODS: Twelve treatment naive patients with biopsy proven
      NSCLC underwent (18)F-FLT PET/CT scans followed by lobectomy were enrolled. The
      surgical specimen was dissected into 4-7 MUm sections at approximately 4-mm
      intervals. The best slice was sort out to complete Ki-67 staining. Maximum Ki-67
      labelling Index and SUVmax of the corresponding PET image was calculated. The
      correlation between Ki-67 Labelling Index and SUVmax of FLT was determined using
      Spearman Correlation analysis. High uptake areas and high proliferating areas
      were delineated on the two images, respectively, and their location was compared.
      RESULTS: The maximal SUV was 3.26 +/- 0.97 (1.96-5.05), maximal Ki-67 labeling
      index was 49% +/- 27.56% (5%-90%). Statistical analysis didn't reveal a
      significant correlation between them (r = -0.157, P = 0.627, > 0.05). 9 patients
      can contour high proliferating area on Ki-67 staining slice, and eight can
      contour the high uptake areas. In 4 patients, we can observe a generally close
      distribution of high uptake areas and high proliferating areas, in one patient,
      both the uptake level and proliferation status was low, while the others didn't
      not find a significant co-localization. CONCLUSION: Noninvasive (18)F-FLT PET
      assessing the proliferative status may be a valuable aid to guide dose painting
      in NSCLC, but it needs to be confirmed further.

PMID- 26309654
TI  - Cuffed-tunneled hemodialysis catheter survival and complications in pediatric
      patients: a single-center data analysis in China.
AB  - This study aims to evaluate the outcome and complications of cuffed-tunneled
      catheters in pediatric patients. Between January 2010 and December 2013, 16
      pediatric patients with end-stage renal disease (ESRD) were included. 21 cuffed
      tunneled hemodialysis catheters were inserted in patients for long-term
      hemodialysis access. No serious complications were observed in all patients
      receiving catheter insertion operation, except one with hemopneumothorax. Median
      survival time was 413.5 days, with rate being 67.5% in the first year, 51.5% in
      the second year and 43.6% in the third year. Among attempted catheter insertions,
      21 (100%) achieved successful vascular access with 13 (61.9%) being remained for
      the required period and 8 (38.1%) being removed due to death, intractable blood
      or tunnel infections, catheter thrombosis or malposition. The overall rate of
      catheter-related infections, thrombosis and malposition was 7.3, 23.4 and 3.4
      episodes/1000 catheter days, respectively. Cuffed-tunneled hemodialysis catheters
      could be effectively used for maintenance of hemodialysis vascular access for
      pediatric patients with ESRD. Various surveillance measures should be taken to
      ensure cuffed-tunneled catheters' long-term patency. 

PMID- 26309655
TI  - Clinical and electrophysiological studies of botulinum toxin type A to treat
      hemifacial spasm complicated with auricular symptoms.
AB  - OBJECTIVE: To investigate the involvement of posterior auricular muscle (PAM) and
      the effect of botulinum toxin type A (BTX-A) injection into PAM in patients with
      hemifacial spasm (HFS) complicated with auricular symptoms. METHODS: Sixty-three
      consecutive HFS patients complicated with auricular symptoms such as tinnitus or
      murmur, "ticking" or a "clicking" sound and discomfort on the same side, who were
      referred to our department between July 2009 and January 2010, were enrolled. The
      diagnosis of idiopathic HFS was made clinically. The patients were largely
      randomized into two BTX-A treatment groups according to the order of referral.
      The first group included 33 cases where the injection sites were routinely
      located at the frontal, orbicularis oculi, zygomaticus and buccinator muscles
      while the other was the PAM group, which included 30 cases, where 4 units of BTX
      A were additionally injected into the PAM prior to injection at other sites. A
      test of blink reflex was performed and the lateral spread of blink reflex to the
      orbicularis oris (OO) and PAM, i.e. abnormal muscle response (AMR), was recorded
      and the peak-peak amplitude of AMR was measured. The patients were followed up
      clinically and electrophysiologically for at least 4 weeks (29.47 +/- 2.53 days).
      RESULTS: 1) Before injection, the latencies of R1, R2, R2' were normal, there was
      no significant difference between uninjured and affected side; The amplitudes of
      R1, R2, R2' in affected side were higher. 2) After injection, there was no
      significant change of the R1, R2 and R2' latencies; The amplitudes of R1, R2 and
      R2' decreased significantly. 3) Patients reported that their auricular symptoms
      subsided after injection in both groups; The remission rate was 45.5% (15/33) and
      76.7% (23/30) in the regular and PAM group, respectively, with a higher rate in
      the PAM group (chi(2) = 6.40, P = 0.011). 4) In both groups the AMR amplitude
      decreased significantly after injection. In the regular group, the respective OO
      amplitudes (MUV) before and after injection were 304.00 +/- 30.34 and 129.33 +/-
      9.59 (t = 5.820, P = 0.000), and for PAM the amplitudes were 298.00 +/- 33.28 and
      184.67 +/- 20.21 (t = 2.818, P = 0.014); in the PAM group, the before and after
      injection OO amplitudes were 405.33 +/- 66.71 and 116.00 +/- 9.99 (t = 4.214, P =
      0.001), and for PAM they were 390.00 +/- 53.58 and 72.00 +/- 9.67 (t = 6.011, P =
      0.000), respectively. 5) PAM amplitudes in the PAM group decreased more
      significantly after BTX-A injection compared with those in the regular group (t =
      4.237, P = 0.001). CONCLUSIONS: The treatment on HFS with local injection of BTX
      A is very effective. In HFS complicated with auricular symptoms patients,
      electrophysiological studies are helpful for guiding treatment plans, and the
      auricular symptoms could be improved by BTX-A injection into the PAM in addition
      to the regular injection sites.

PMID- 26309656
TI  - Effect of percutaneous renal sympathetic nerve radiofrequency ablation in
      patients with severe heart failure.
AB  - This study aimed to investigate the clinical feasibility and effects of
      percutaneous renal sympathetic nerve radiofrequency ablation in patients with
      heart failure. A total of 20 patients with heart failure were enrolled, aged from
      47 to 75 years (63+/-10 years). They were divided into the standard therapy (n =
      10), and renal nerve radiofrequency ablation groups (n = 10). There were 15 males
      and 5 female patients, including 8 ischemic cardiomyopathy, 8 dilated
      cardiomyopathy, and 8 hypertensive cardiopathy. All of the patients met the
      criteria of New York Heart Association classes III-IV cardiac function. Patients
      with diabetes and renal failure were excluded. Percutaneous renal sympathetic
      nerve radiofrequency ablation was performed on the renal artery wall under X-ray
      guidance. Serum electrolytes, neurohormones, and 24 h urine volume were recorded
      24 h before and after the operation. Echocardiograms were performed to obtain
      left ventricular ejection fraction at baseline and 6 months. Heart rate, blood
      pressure, symptoms of dyspnea and edema were also monitored. After renal nerve
      ablation, 24 h urine volume was increased, while neurohormone levels were
      decreased compared with those of pre-operation and standard therapy. No obvious
      change in heart rate or blood pressure was recorded. Symptoms of heart failure
      were improved in patients after the operation. No complications were recorded in
      the study. Percutaneous renal sympathetic nerve radiofrequency ablation may be a
      feasible, safe, and effective treatment for the patients with severe congestive
      heart failure. 

PMID- 26309657
TI  - Relationship between cytokine gene polymorphisms and recurrent spontaneous
      abortion.
AB  - Recurrent spontaneous abortion (RSA), defined as three or more sequential
      abortions before the twentieth week of gestation. Some studies have led to the
      awareness that immunological factors play an important role in establishing a
      successful pregnancy. The aim of present study was to investigate the
      relationship between RSA and polymorphisms of cytokine genes coding for TNF-alpha
      (-308 G->A, -238 G->A), TNF-beta (+252 G->A) as Th1 or pro-inflammatory factors
      as well as IL-6 (-634 G->C, -174 G->C), IL-10 (-1082 A->G, -819 C->T, -592C->A)
      as Th2 cytokines in women with RSA compared with healthy women. A total of 284
      women with RSA and 284 control women with at least two successful pregnancies and
      no history of abortion were included in the study. The polymerase chain reaction
      (PCR), allele-specific oligonucleotide polymerase chain reaction (ASO-PCR) or PCR
      RFLP (restriction fragment length polymorphism) methods were used for genotyping.
      In addition, the ELISA was conducted to investigate four cytokine serum levels in
      women with RSA and healthy women. Results showed that: TNF-alpha -308G/A, IL-6 
      174 G/C and IL-10 -819 G/C polymorphisms showed statistically significant
      differences between the RSA patients and controls (P=0.008, P=0.0005 and P=0.03
      separately). Levels of four cytokines in the serum showed that there were no
      significant differences in TNF-alpha and TNF-beta between patients and control
      (P>0.05), while the level of IL-6 and IL-10 were lower than control group and the
      differences were statically significant (P<0.05). This study demonstrated a
      possible association between TNF-alpha -308, IL-6 -174 and IL-10 -819 promoter
      polymorphism and RSA. 

PMID- 26309658
TI  - IL-17A G197A gene polymorphism contributes to susceptibility for liver cirrhosis
      development from patients with chronic hepatitis B infection in Chinese
      population.
AB  - BACKGROUND: IL-17A G197A and IL-17F A7488G gene polymorphisms are found to be
      associated with the risk of several diseases, however few studies have focused on
      their correlation with risk of liver cirrhosis (LC). AIMS: The aim of this study
      was to assess the impact of IL-17A G197A and IL-17F A7488G gene polymorphisms on
      development of LC from chronic hepatitis B (CHB) in Chinese patients. METHODS: A
      total of 163 HBV-related LC patients and 168 CHB patients were enrolled in the
      present study. IL-17A and IL-17F gene polymorphisms were analyzed using a
      polymerase chain reaction (PCR) restriction fragment length polymorphism assay
      (PCR-RFLP). RESULTS: Frequencies of IL-17A G197A genotype AA and allele A were
      significantly higher in LC patients compared with that in CHB patients (AA 42.33%
      vs 27.98%, P = 0.032; A 56.34% vs 46.15%, P=0.011, respectively); While no
      significant difference in frequencies of genotypes and alleles of IL-17F A7488G
      was found between the two groups. The AA genotype of IL-17A G197A significantly
      increased LC risk (OR 4.186, 95% CI: 1.479-11.844), while A allele carriers were
      also associated with an increased LC risk (OR 1.856, 95% CI: 1.161-2.967).
      CONCLUSION: IL-17A G197A is a candidate gene that confers the genetic
      susceptibility for LC development from CHB in Chinese population.

PMID- 26309659
TI  - Visfatin expression and genetic polymorphism in patients with traumatic brain
      injury.
AB  - OBJECTIVE: To discover the expression of visfatin and its genetic mutation and
      clinical significance in patients with traumatic brain injury. METHODS: 99 cases
      of traumatic brain injury patients admitted to Chongqing Emergency Medical Center
      from June 2013 to December 2014. There were 56 male and 43 female with an average
      age of 45.2 years. Through diagnosis, the 99 patient's conditions were all
      relatively in accordance with traumatic brain injury standard; meanwhile, the
      patients were divided into mild, moderate and severe traumatic brain injury
      according to GCS criteria when they admitted to clinics. 33 people were enrolled
      in each group. To highlight the results, 40 healthy people were enrolled in the
      control group with 25 males and 15 females. ELISA was used to detect serum
      visfatin level in 99 patients. Single base extension was used to detect visfatin
      gene promoter -1535C/T polymorphism. RESULTS: By examination we found that
      visfatin gene -1535C > T locus had three genotypes: TT, TC and CC, respectively.
      By examination we obtained that genotype distribution and allele frequency showed
      no significance between the experimental group and the control group (P > 0.05).
      Through analysis we can get that serum visfatin level in patients with traumatic
      brain injury was significantly higher than that in the control group. CC genotype
      are mostly patients with severe traumatic brain injury, and its serum visfatin
      level was higher than that with CT and TT genotype (all P < 0.05). CT and TT
      genotype carriers were most mild and moderate traumatic brain injury patients.
      CONCLUSION: Expression of visfatin and its gene mutation in patients with
      traumatic brain injury were closely related to the severity of the disease.

PMID- 26309660
TI  - Could Harmonic Scalpel (Ultracision(r)) be considered the best device in surgical
      treatment of vulvar cancer of patients with implanted pace-maker? Proposal and
      rationale.
AB  - Vulvar cancer (VC) represents about 4% of gynecologic malignancies, its incidence
      increases with age and peak incidence is found between 70-79 years. In cases of
      locally advanced disease surgery is often required and radical vulvectomy, with
      or without mono-bilateral inguino-femoral lymphadenectomy, is standard
      management. Various devices have been implemented in gynecological surgery in an
      attempt to minimize or avoid frequent intra/postoperative complications linked to
      energy use, unfortunately the majority of these devices require monopolar or
      bipolar energy. Ultracision(r) represents a unique surgical device capable of
      performing both cutting and coagulation at different intensities without use of
      electric energy. The use of Ultracision(r) in the radical treatment of VC has
      advantages both in terms of intraoperative and postoperative complications
      responsible for the reduction of surgical time and blood loss, complete tissue
      removal according to oncological criteria, diminished desensitization of
      peripheral areas and reduction of wound complications. These advantages have been
      widely demonstrated and contribute to making Ultracision(r) a cost-effective
      option in the routine treatment of patients affected by vulvar cancer especially
      when considering its safety in cardiopathic patients with implanted pacemaker. If
      the impressive results achieved in radical vulvar surgery will be confirmed,
      scalpel use could be proposed as routine for surgery of the routinely in surgical
      approach of vulvar and perineal area, in both benign and malignant disease. 

PMID- 26309661
TI  - Correlation analysis of anxiety status and sub-health status among students of 13
      26 years old.
AB  - The purpose of the survey is to investigate the relationship between anxiety
      statuses and suboptimal health status among students from south of Anhui in
      china. Our study was a population-based, cluster sampling method survey with a
      sample consisting of 5249 students, who come from a university, four high schools
      and four middle schools in Wannan Area in China. Sub-health status was measured
      by multidimensional sub-health questionnaire of adolescents, and anxious status
      was assessed using anxiety self-assessment scale. A total of 538 (10.25%) of the
      students were detected with anxiety status, the prevalence of anxiety status for
      boy and girl students were 11.8% and 16.5%,respectively, there are no significant
      difference between urban and rural for the anxiety score in physical and mental
      sub-health status (P > 0.05). The boys living in urban have a lower anxiety score
      than that of the girls, the no-only child and child living in rural in different
      sub-health status (P < 0.05). The results indicate that sub-health status and
      anxiety status are prevalent among students, especially in girls, no-only child
      and students who living in rural area, the school heads should pay more attention
      to the mental health of students. 

PMID- 26309662
TI  - Safe and effective guidance by intracardiac echocardiography for transcatheter
      closure in atrial septal defects.
AB  - The aim of this study was to investigate the clinical outcome of intracardiac
      echocardiography (ICE) for transcatheter closure of atrial septal defect (ASD)
      compared with the trans-esophageal echocardiography (TEE) guided method. From May
      2010 to April 2011, 46 patients who underwent ICE guided (n = 23) or TEE guided
      (n = 23) transcatheter closure of ASD were analyzed retrospectively. We compared
      the demographic characteristic, procedure parameters and outcomes between ICE-
      and TEE-guided groups. No significant difference was found between 2 groups on
      demographic characteristics. Fluoroscopy time and procedure time was
      significantly decreased in ICE guided group than that in TEE-guided group. In
      addition, no significant difference was found on treatment outcomes,
      complications between these 2 groups. ICE-guided ASD occlusion is safe and
      effective method, which provides more accurate anatomical information, shorter
      fluoroscopy time and procedure time. 

PMID- 26309663
TI  - Diagnostic value of CYFRA 21-1 and CEA for predicting lymph node metastasis in
      operable lung cancer.
AB  - Tumour markers are used extensively for the management of lung cancer, including
      diagnosis, evaluating effectiveness of treatments, monitoring recurrence after
      therapy and for predicting prognosis. However, there exists a knowledge gap
      regarding potential quantitative correlations between tumour marker levels and
      the extents of lymph node involvement in primary lung cancer. The current study
      is comprised of 139 lung cancer patients scheduled to undergo surgical operation.
      Of the 139 patients, 107 were subsequently diagnosed with lung cancer without
      lymph node involvement and 32 were diagnosed with malignant disease with lymph
      node involvement by histological examination. Preoperative tumour marker levels
      were quantified in each patient. The median tumour marker levels were
      statistically higher in lung cancer patients with malignant lymph nodes than in
      those who suffered either benign lung disease or carcinoma in situ (Kruskal
      Wallistest; P = 0.001). Tumour marker levels were significantly correlated with
      clinical stage (ANOVA; P = 0.009). When examined as a dichotomous variable (CYFRA
      21-1 <= 5.0 and CEA <= 5.0 group and CYFRA 21-1 > 5.0 or CEA > 5.0 group),
      elevated tumour marker levels correlated strongly with the presence of positive
      lymph nodes (chi(2) test; P = 0.000). This correlation suggests that the tumour
      marker levels are clinical predictors for the malignant involvement of lymph
      nodes in operable lung cancer patients. 

PMID- 26309664
TI  - The evaluation of clinical therapy effects of oral western medicine combined with
      magnetic pulse acupoint stimulation in treating elderly patients with coronary
      heart disease.
AB  - OBJECTIVE: Treat the patients suffered from coronary heart disease with oral
      western medicine, combining with magnetic pulse acupoint stimulation, and observe
      the therapeutic effects of such combination therapy method. METHODS: 56 old
      people with coronary heart disease are randomly divided into a treatment group
      and a control group. Both groups of patients are treated by the routine drugs, in
      addition, the patients of the treatment group are treated by magnetic pulse
      therapy additionally. Compare clinical symptoms, blood lipid and blood
      rheological indexes of the patients in the two groups when they are selected and
      after 30 days' treatment. RESULTS: after 30 days' treatment, it is found that
      clinical symptoms, blood lipid and blood rheological indexes of the patients in
      the treatment group are significantly improved compared with those when they are
      selected and those of the control group (P<0.05). CONCLUSION: patients with
      coronary heart disease, treated by pulsed magnetic therapy and the conventional
      drug intervention, had relieved synptom, improve blood lipid and heart blood
      supply function.

PMID- 26309665
TI  - Impacts of parathyroidectomy on renal anemia and nutritional status of
      hemodialysis patients with secondary hyperparathyroidism.
AB  - The aim of this study was to investigate the impacts of parathyroidectomy (PTX)
      towards the renal anemia and nutritional status of hemodialysis patients with
      secondary hyperparathyroidism (SHPT). 32 patients, enrolled into the blood
      purification center of our hospital for the hemodialysis treatment, were
      collected and divided into the PTX group and the non-PTX group, with 16 patients
      in each group. The changes of relevant indicators such as immunoreactive
      parathyroid hormone (iPTH), anemia and nutrition were observed before, 1-, 3-, 6
      month after the treatment. The contents of iPTH, Ca, P and Ca * P of the PTX
      group decreased rapidly 1 month after the surgery; while Hb and Hct increased
      significantly from the 1st postoperative month; the dosage of EPO was
      significantly reduced 3-month after the surgery; the content of Alb gradually
      increased from the 3(rd) postoperative month; the content of TG decreased
      significantly from the 6(th) postoperative month; while the contents of BMI and
      TSF increased significantly from the 6(th) postoperative month, which exhibited
      the statistically significant differences when compared with the preoperative and
      the non-PTX group (P < 0.05). PTX could quickly reduce the iPTH level and
      significantly improve the renal anemia and nutritional status; SHPT was the
      important factor that would affect the renal anemia and malnutrition; PTX could
      reduce the amount of EPO, and reduce the economic burden of patients. 

PMID- 26309666
TI  - Clinical implications of multifocality as a prognostic factor in breast carcinoma
      - a multivariate analysis study comprising 460 cases.
AB  - BACKGROUND: Multifocality is not listed among prognostic factors in international
      breast cancer guidelines. This study aims to analyze survival in multiple breast
      carcinomas (MFMC cc) compared to unifocal ones (UF cc), in order to assess the
      prognostic impact of multifocality. METHODS: The study included 460 breast
      carcinomas (2002-2006) with a median follow-up time of 104 months (74-134
      months). We assessed mortality rates, overall survival at 5 years and 10 years in
      general, overall survival at 5 and 10 years in MFMC cc compared to UF cc, as well
      as median survival and survival rate according to age, T status and axillary
      lymph node status in MFMC cc compared to UF cc. We carried out a multivariate
      analysis in order to identify independent predictor factors for survival.
      RESULTS: 69/460 (15%) of cases were MFMC cc. Mortality rates were 56.5% in MFMC
      cc versus 45.1% (UF cc) (P = 0.08). 5-year overall survival was 55.9% in MFMC cc
      vs. 64.7% UF cc, and the 10-year overall survival was 34.9% MFMC cc vs. 52.7% UF
      cc (P = 0.27). Median survival in MFMC cc was 78 months (6.5 years), whereas in
      UF cc it was 126 months (10.5 years). However, in the multivariate analysis,
      survival was independently influenced only by tumor size and the presence of
      axillary lymph node metastases (P < 0.0001). CONCLUSION: Breast cancer
      multifocality is associated with higher general mortality rates, lower 5 and 10
      year overall survival, yields a lower median survival, but it does not constitute
      an independent prognostic factor in multivariate analysis.

PMID- 26309667
TI  - Prevalence of oral Candida carriage and Candida species among cigarette and maras
      powder users.
AB  - OBJECTIVE: The aim of this study was to determine the prevalence of Candida
      carriage and Candida species among cigarette and Maras powder (MP) users.
      MATERIAL AND METHODS: This study was conducted on 180 volunteering men in 20
      cafehouses in the city of Kahramanmaras, Turkey. The sociodemographic
      characteristics of the participants and the behaviors of MP and cigarette usage
      were noted down. Culture specimens were obtained from bilateral buccal mucosa and
      dorsum of the tongue with a sterile cotton-tipped swap. RESULTS: The specimens
      were inoculated into Sabouraud Dextrose Agar. The mean age of the participants
      was 40.49 +/- 12.89 years (min = 18, max = 87). Fifty-eight percent of the
      cigarette users, 56.7% of the MP users, and 36.7% of the control group were
      Candida carriers. The difference of Candida carriage between cigarette and MP
      users and the control group was statistically significant (P = 0.018 and P =
      0.029 respectively). The prevalence of Candida carriage was similar between
      cigarette and MP users (P = 0.854). The most frequently isolated species was
      Candida albicans at a rate of 30% in the cigarette users' group, 28.3% in the MP
      users' group and at a rate of 18.3% in the controls. The prevalence of Candida
      tropicalis carriage was found to be at a rate of 20% in cigarette and 21.7% in
      the MP users' group compared to 11.7% in the nonusers. CONCLUSIONS: In the
      present study we found that the prevalence of oral Candida carriage was
      significantly higher among cigarette and MP users.

PMID- 26309668
TI  - Comparative study on short-term and long-term prognostic determinants in patients
      with acute cerebral infarction.
AB  - BACKGROUND: At present, there are many studies on prognostic determinants in
      patients with acute cerebral infarction, while studies on short-term and long
      term prognostic determinants are less. The purpose of this study was to explore
      the short-term and long-term association and same and different points of
      prognostic determinants in patients with acute cerebral infarction for guiding
      clinical treatment. METHODS: 201 patients with acute cerebral infarction were
      included in the study, whose neurological functions were assessed via National
      Institute of Health Stroke Scale (NIHSS) within 24 h and computed tomography or
      magnetic resonance imaging were performed within 48 h of symptom onset. All of
      the patients were administered with same medication regimen (including medication
      and rehabilitation). The NIHSS and the modified Rankin Scale were used to assess
      the extent of disability at 15 d after admission and one year, respectively.
      Short-term and long-term prognostic determinants and its association were
      analyzed by single and multivariable logistic regression. RESULTS: Infarct volume
      correlated with short-term prognosis (OR = 3.543, 95% CI: 1.632~10.212), while it
      showed no correlation with long-term prognosis; concurrent infection was
      independent risk factor for short-term prognosis of acute cerebral infarction (OR
      = 2.532, 95% CI: 1.803~6.886). Baseline NIHSS score independently correlated with
      short-term and long-term prognosis (odds ratio, respectively: OR = 1.880, 95% CI:
      1.462~6.679; OR = 1.761, 95% CI: 1.372~6.758); gender (OR = 0.311, 95% CI:
      0.140~0.681) and basal ganglia infarction (OR = 2.263, 95% CI: 1.349~11.662) were
      independently associated with long-term prognosis, while it showed no significant
      correlation with short-term prognosis. Short-term prognosis effect was an
      independent predictor for long-term prognosis (OR = 0.487, 95% CI: 0.141~0.895).
      Age, hospitalization time, short-term and long-term prognosis of patients showed
      no significant correlation. CONCLUSION: There were differences between short-term
      and long-term prognosis of acute cerebral infarction. Short-term prognosis effect
      was an independent predictor for long-term prognosis. For controllable factors,
      active intervene should be taken in order to improve prognosis of patients.

PMID- 26309669
TI  - Effects of epidural preemptive analgesia on stress reaction in retroperitoneal
      laparoscopic adrenalectomy surgery: a randomized controlled study.
AB  - OBJECTIVE: To compare the effects of general anesthesia combined with epidural
      preemptive analgesia with general anesthesia on stress reaction in the
      retroperitoneal laparoscopic surgery. METHODS: Forty patients with adrenal tumors
      undergoing retroperitoneal laparoscopic surgeries were randomly assigned into
      general anesthesia combined with epidural preemptive analgesia group (GE) and
      general anesthesia group (G). Each group had 20 cases. In the GE group, before
      the induction of general anesthesia, T10-T11 epidural puncture was performed and
      0.2% bupivacaine 5-10 ml was injected to maintain the anesthesia level at T4. In
      the G group, normal saline was injected as control. After entry into the
      operation room (X0), before surgery (X1), 30 min after pneumoperitoneum (X2), 60
      min after pneumoperitoneum (X3), 10 min after extubation (X4), the mean arterial
      pressure (MAP) and heart rate (HR) were recorded. The concentration of plasma
      endothelin (ET) and calcitonin gene-related peptide (CGRP) were detected.
      Meanwhile, isoflurane inhalation MAC and intervention situations were recorded.
      RESULTS: At X1-X3, MAP in the GE group was significantly lower than that in the G
      group (P < 0.05). At X2-X4 HR in two groups was significantly faster than at X1
      (P < 0.05). At X4 HR in the GE group was significantly lower than that in the G
      group (P < 0.05). At X3 and X4, ET and CGRP were significantly lower than those
      in the G group (P < 0.05). At X2 and X3, ET in the GE group was significantly
      higher than that at X1 (P < 0.05). At X3, CGRP in the GE group was significantly
      higher than that at X1 (P < 0.05). At X2, X3 and before pneumoperitoneum,
      isoflurane MAC in the GE group was significantly lower than that in the G group
      (P < 0.05). At X2 and X3, isoflurane MAC in two groups was significantly higher
      than that during pneumoperitoneum (P < 0.05). CONCLUSION: Compared with general
      anesthesia, general anesthesia combined with epidural preemptive analgesia can
      effectively alleviate patients' stress reaction under retroperitoneal
      laparoscopic surgery.

PMID- 26309670
TI  - Comparison of lumbar spine stabilization exercise versus general exercise in
      young male patients with lumbar disc herniation after 1 year of follow-up.
AB  - OBJECTIVE: The safest and most effective conservative treatment for patients with
      lumbar disc herniation (LDH) has not been established. The purpose of this study
      was to evaluate the effect of lumbar spine stabilization exercise (LSSE) and
      general exercise (GE) on pain intensity and functional capacity in young male
      patients with LDH. METHODS: Sixty-three young male adults aged 20 to 29 years
      with the diagnosis of LDH were enrolled and divided into an LSSE group (n=30) and
      a GE group (n=33). Patients in both groups received low-power laser (LPL) therapy
      during the first week of the onset of LDH. Patients in the GE group underwent a
      GE program. Patients in the LSSE group followed an LSSE program for 3 months. All
      of the patients were subjected to pain intensity and functional capacity
      evaluations four times: at pre-and post-LPL therapy, and at 3 months and 1 year
      post-exercise. Pain intensity of the lower back and legs was evaluated with the
      visual analogue scale (VAS), and functional capacity was evaluated with the
      Oswestry Disability Index (ODI). RESULTS: Both groups showed a significant
      reduction in VAS and ODI scores at 3 and 12 months post-exercise compared with
      before treatment (P<0.001). The LSSE group showed a significant reduction in the
      average score of the VAS for low back pain (P=0.012) and the ODI (P=0.003) at 12
      months post-exercise compared with the GE group. CONCLUSIONS: LSSE and GE are
      considered as effective interventions for young male patients with LDH. Moreover,
      LSSE is more effective than GE, and physical therapy, such as LPL, is required
      during acute LDH.

PMID- 26309671
TI  - Comparison of simultaneous systemic steroid and hyperbaric oxygen treatment
      versus only steroid in idiopathic sudden sensorineural hearing loss.
AB  - A retrospective chart review to assess the effectiveness of hyperbaric oxygen
      treatment in sudden sensorineural hearing loss. 44 patients aged between 17-67
      years diagnosed with idiopathic sensorineural hearing loss less than 30 days were
      admitted to our clinic Patients were treated with systemic steroid alone or
      systemic steroid plus hyperbaric oxygen therapy. In the comparison of two groups,
      there was no statistically significant difference of audiometric evaluation
      (P>0.0028) found in hearing improvement for each frequency on 5th day of the
      treatment and post treatment. Age (<=45 and >45) and initial hearing level (<=60
      dB. And >60 dB.) does not seem to be an influential factor according to the
      results of the study (P>0.0007). The present study did not show more superior
      healing effect of hyperbaric oxygen therapy added to systemic steroid therapy
      than steroid infusion alone. The results are consistent with those of some
      papers. However there are also conflicting data that support significant effect
      of hyperbaric oxygen therapy. Routine administration of this therapy seems to be
      unnecessary in view of these results. 

PMID- 26309672
TI  - Health related management plans improve sleep disorders of patients with chronic
      liver disease.
AB  - BACKGROUNDS: Sleep disorders (SDs) are commonly occurred in patients with chronic
      liver disease (CLD) and always bring with uncomfortable experience Lavender hot
      bathing, foot-soaking, or progressive relaxation have been widely used to provide
      comfortable feeling for CLD patients and promote their sleep quality. AIMS: Thus,
      the aim of present study is to investigate effective intervention from above
      mentioned in the managements of SD and promote sleep quality for CLD patients.
      METHODS: This study was conducted in People's Liberation Army No. 302 Hospital. A
      total of 317 subjects joined in our research. Initially, 197 CLD patients were
      enrolled and divided randomly into four groups for receiving lavender hot-bathing
      and foot-soaking, progressive relaxation, or the combination of both methods, and
      controls. After that, all of enrolled subjects were given sleep state
      questionnaires to assess their sleep qualities and other associated factors. Self
      rating scores of sleep (SRSS) was sued to assess sleep disorder. Furthermore,
      another cohort with 120 CLD patients were also investigated for further
      confirming related findings. RESULTS: The SRSS scores were significantly higher
      in the patients with CLD (62.94%) than those of domestic common model and
      internal medicine inpatients. However, all three methods of intervention were
      effectively decreased SRSS scores. The four mostly influencing factors of sleep
      states were short sleep, difficulty falling asleep, staying asleep and early
      morning awakening. Besides, age was identified as one of associating with sleep
      states. 44.67% of patients suffered from polyuria, abdominal distention or itch
      of skin. And those factors contributed to major risk factors of sleep disorder.
      Furthermore, sleep states also influenced by environmental interference (37.06%).
      CONCLUSION: The health managements of health education could reduce risk factors
      and implement intervention strategies, effectively decreased occurrence of sleep
      disorder related symptoms.

PMID- 26309673
TI  - KCNA5 gene polymorphism associate with idiopathic atrial fibrillation.
AB  - OBJECTIVE: To investigate the correlation between KCNA5 single nucleotide
      polymorphism (SNP) and idiopathic atrial fibrillation (IAF). METHODS: A case
      control study was conducted, including 282 cases of IAF patients and 300 cases of
      age and sex-matched normal controls; gene sequencing method was used to detect
      the distribution of KCNA5 SNP (rs3741930 and rs1056468) in the two groups. The
      IAF patients were divided into two groups based on the different genotypes of
      rs1056468 and rs3741930; differences in clinical parameters between the two
      groups of patients were compared. RESULTS: For rs3741930, the CC, CT and TT
      genotype frequencies in the IAF group were 16.7%, 50.0%, and 33.3% respectively;
      C allele frequency in IAF group was 41.7%; in the normal control group, those
      were 10.0%, 49.3%, 40.7% and 34.7% respectively; CC genotype frequency and C
      allele frequency in IAF group were significantly higher compared with the control
      group (P=0.019, P=0.014). For rs1056468, the AA, AT and TT genotype frequencies
      in the IAF group were 44.3%, 48.6%, and 7.1% respectively; in 300 cases of normal
      controls, those were 38.7%, 50.7%, and 10.6% respectively; A allele frequency in
      IAF group was 68.6 %, and it was 64.0% in normal controls. There were no
      significant differences in genotype and allele frequencies between control and
      IAF groups (P>0.05). In IAF group, among different genotypes of rs1741930 and
      rs1056468, there were no significant differences in age, SBP, DBP, HR, LAD and
      LVEF (P>0.05). While the BMI in CC and CC+TT groups of rs3741930 locus were
      26.9+/-2.3 Kg/m(2) and 24.8+/-2.5 Kg/m(2) respectively. There were statistical
      differences between the two groups (P=0.019). BMI in AA and AA+TT groups of
      rs1056468 locus were 24.9+/-2.7 Kg/m(2) and 26.4+/-2.4 Kg/m(2) respectively;
      There was statistically significant significance between the two groups
      (P=0.014). CONCLUSION: The single nucleotide polymorphism rs3741930 locus in
      KCNA5 gene was related to the risk of IAF; the population carrying C allele was
      more susceptible to IAF; the polymorphic loci, rs3741930 and rs1056468, were
      correlated with the BMI of IAF patients.

PMID- 26309674
TI  - Warfarin dosage adjustment strategy in Chinese population.
AB  - BACKGROUND: Blood anticoagulation after heart valve replacement is a recognized
      difficulty all over the world. In this study, we identified the effect of
      amiodarone on the function of warfarin and confirmed the countermeasure by
      concluding the genotype distribution of vitamin K epoxide reductase complex 1
      (VKORC1) and cytochrome P450 2C9 (CYP2C9) of the patient to predict the security
      dose of warfarin. METHODS: Studying on the VKORC1 (-1639G>A) and CYP2C9 genotype
      of 271 cases on heart valve replacement in the First Affiliated Hospital of
      Soochow University from Jan. 2012 to Jan. 2014. Warfarin's multivariable
      regression equation was taken to calculate their warfarin dosage. In the study,
      80 of them were selected and divided into 4 groups according to their different
      warfarin dosage and their usage of amiodaron. The differences of INR values at
      the 5(th), 8(th), 11(th), 14(th) days of operation were analyzed. RESULTS: Among
      the 80 cases, VKORC1 (-1639G>A) AA types accounted for 90%, and AG types
      accounted for another 10%, while GG types were not found. In addition that, all
      of the patients (100%) had CYP2C9*1/*1 type, and CYP2C9*1/*3 had not appeared.
      There was significant difference in INR values between the groups who used
      amiodarone or not. The pharmacogenetic equation was accurate in the predicting of
      the warfarin dosage, so that satisfied anticoagulation efficacy had been achieved
      in 2 weeks after surgery. CONCLUSION: It is necessary for the patients to do the
      warfarin pharmacogenetic test to get the suitable dose before heart valve
      replacement. Amiodarone can enhance the anticoagulant efficacy of warfarin, so
      the dosages of warfarin should be reduced properly because of the medicine
      combination, and INR values must be monitored more frequently to make the
      anticoagulant process secure and efficient.

PMID- 26309675
TI  - Lung microenvironment promotes the metastasis of human hepatocellular carcinoma
      cells to the lungs.
AB  - Cancer metastasis is a highly tissue-specific and organ-selective process. It has
      been shown that the affected tissues and/or organs play a major role in this
      complex process. The lung is the most common target organ of extrahepatic
      hepatocellular carcinoma (HCC) metastasis, but the precise molecular mechanism
      underlying this organ-specific metastasis remains unclear. We hypothesized that
      lung microenvironment was able to promote the metastasis of HCC cells to the
      lungs leading to distant metastases. In support of our hypothesis, we provided
      evidence from targeted metastasis in various types of cancer and contributing
      factors in the microenvironment of targeted tissues/organs. A better
      understanding of the steps involved in the interplay between HCC cells and lung
      microenvironment may offer new perspectives for the medical management of lung
      metastases of HCC. 

PMID- 26309676
TI  - Conspicuous effect on treatment of mild-to-moderate COPD by combining deep
      breathing exercise with oxygen inhalation.
AB  - Chronic obstructive pulmonary disease (COPD) can lead to respiratory failure, but
      current pharmacological treatments focus on symptom relief or slowing disease
      progression. Here, the effectiveness of an alternative therapy combining deep
      breathing exercises and oxygen inhalation therapy was assessed in mild-to
      moderate COPD patients. Forty-two male mild-to-moderate COPD patients were
      randomly divided into a deep-breathing training group, an oxygen inhalation
      group, and a combination group (n=14 in each). In the deep-breathing training
      group, the patients were treated only by the deep-breathing exercise; in the
      oxygen inhalation group, the patients were treated only by oxygen inhalation; in
      the combination group, the patients were treated by combining the deep-breathing
      exercises with oxygen inhalation. Before treatment, there were no statistical
      differences in the general characteristics or lung function indexes between the
      three groups of patients (P > 0.05). However, after treatment, patients in the
      combination group had significantly better lung function indexes than they did
      before treatment, and their improvement was also superior to that of patients
      from the deep-breathing training group and the oxygen inhalation group (P < 0.01
      and P < 0.05, respectively). Thus, a treatment method combining deep-breathing
      exercise with oxygen inhalation offers more significant lung function improvement
      in COPD patients than either the deep-breathing exercise or oxygen inhalation
      alone. This approach should be further explored for use in the clinic. 

PMID- 26309677
TI  - Using foci number to predict central lymph node metastases of papillary thyroid
      microcarcinomas with multifocality.
AB  - OBJECTIVES: The aim of our study is to analyze the clinicopathological
      characteristics and treatment options for papillary thyroid microcarcinomas with
      multifocality and investigated whether the number of foci in papillary thyroid
      microcarcinomas with multifocality can predict central lymph node metastases.
      Methods Records of 329 consecutive PTMC patients with multifocality, and who were
      treated surgically between 2003 and 2014 were reviewed. Patients with
      multifocality were identified by histopathology. The number of foci, size of the
      largest tumour, presence of extrathyroidal invasion, infiltration, and other
      clinicopathological parameters were collected and analyzed for all the cases.
      RESULTS: Univariate analysis, age, sex, maximum tumour size, and extrathyroidal
      invasion were found to be significant prognostic factors (P = 0.001, 0.020, <
      0.001, 0.043; respectively). Multivariate analysis found that age, sex, and
      maximum tumour size were independent prognostic factors for CLNM in PTMCs. Among
      them, Male patients (odds ratio 1.887; 95% confidence interval [CI] 1.053-3.380)
      and with maximum tumour size > 0.5 cm (odds ratio 2.819; 95% CI 1.721-4.616) were
      risk factors for increased incidence of CLNM. Patients >= 45 years (odds ratio 0.
      497; 95% CI 0.309-0.800) were less likely to present with CLNM. However,
      extrathyroid invasion was not an independent predictor of CLNM according to our
      results. PTMCs with 2, 3, >= 4 foci had a significantly greater risk of CLNM
      (odds ratio 1.675, 2.360, 2.703; 95% CI 1.195-2.347, 1.425-3.906, 1.411-5.178;
      respectively) compared to PTMCs with unifocality. CONCLUSIONS: Foci numbers were
      linked to an increased incidence of central lymph node metastases in papillary
      thyroid microcarcinomas with multifocality, and we could choose to perform more
      radical treatment in patients with multifocality.

PMID- 26309678
TI  - Effect of APE1 and XRCC1 gene polymorphism on susceptibility to hepatocellular
      carcinoma and sensitivity to cisplatin.
AB  - OBJECTIVE: The relationship between APE1 and XRCC1 gene polymorphism and the
      susceptibility to hepatocellular carcinoma (HCC) was discussed, and the effect of
      APE1 and XRCC1 gene polymorphism on the sensitivity of HCC to cisplatin was
      investigated. METHOD: From January 2010 to August 2014, 118 HCC patients were
      admitted to our hospital. 120 patients treated for non-tumor diseases during this
      period were recruited as controls. PCR-RFLP analyses were performed to determine
      the association between APE1 Asp148Glu and XRCC1 Arg194Trp polymorphism, risk of
      HCC, and sensitivity to cisplatin. RESULTS: The risk of HCC in patients with
      Glu/Glu genotype of APE1 gene was increased by 4.510 times (95% CI: 1.235~16.472,
      P<0.05). Compared with Asp/Asp, the risk of cisplatin resistance in patients with
      Glu/Glu genotype was increased by 10.500 times (95% CI: 1.800~61.241). Compared
      Arg/Arg genotype, the risk of cisplatin resistance in patients with Arp/Trp
      genotype of XRCC1 gene was increased by 6.701 times (95% CI: 1.464~30.732,
      P<0.05). CONCLUSION: APE1 Asp148Glu polymorphism is associated with the
      susceptibility to HCC. APE1 Asp148Glu and XRCC1 Arg194Trp polymorphism plays a
      part in the cisplatin resistance of HCC cells.

PMID- 26309679
TI  - High prevalence of hepatitis B virus infection in primary central nervous system
      lymphoma.
AB  - Primary central nervous system lymphoma (PCNSL) is a rare extranodal form of non
      Hodgkin lymphoma (NHL). The present study aimed to investigate the potential
      association between infection with the Hepatitis B virus (HBV) and PCNSL. The
      prevalence of HBV infection in 199 patients with PCNSL was compared in our
      hospital with that of an age-and sex-matched group of patients with other cancers
      (except liver cancer), and with a national population-based control group. Enzyme
      linked immunosorbent assays were used to test blood samples for HBV markers. It
      was found that the prevalence of HBV infection in PCNSL was 16.1%, which was
      higher as compared with patients with other non-hematologic cancers and the
      national population-based control group. In conclusion, the present study
      demonstrated that PCNSL patients had a higher prevalence of HBV infection and
      suggested a potential association between infection with HBV and PCNSL. 

PMID- 26309680
TI  - Relationship between peripheral blood dopamine level and internet addiction
      disorder in adolescents: a pilot study.
AB  - OBJECTIVES: To explore the association between peripheral blood dopamine level
      and internet addiction disorder (IAD) in adolescents, this could be used to
      explain the neurobiological mechanism of Internet addiction disorder. METHODS: 33
      adolescents with IAD diagnosed by Young's Internet Addiction Test (IAT) and 33
      healthy controls matched by gender and age were investigated in the present
      study. Peripheral blood dopamine levels of the all subjects were determined by
      Enzyme Linked Immunosorbent Assay (ELISA). RESULTS: The difference of peripheral
      blood dopamine level between adolescents with IAD and their controls had reached
      significant level (t = 2.722, P < 0.05). Furthermore, the plasma dopamine level
      was significantly correlated with the Internet Addiction Test score (r = 0.457, P
      < 0.001). The result of rank correlation analysis showed a significant positive
      correlation between the plasma dopamine level and the weekly online time (r =
      0.380, P < 0.01) and there was no significant correlation between the duration of
      Internet use and the plasma dopamine level (r = 0.222, P > 0.05). Binary logistic
      regression analysis showed that DA level and weekly online time were significant
      variables which contribute to internet addiction. CONCLUSIONS: The peripheral
      blood dopamine level is associated with adolescents' internet addiction. The
      present study provided new evidence in favor of the hypothesis that dopamine
      played an important role in IAD.

PMID- 26309681
TI  - Collective rehabilitation training conductive to improve psychotherapy of college
      students with anxiety disorder.
AB  - OBJECTIVE: Study the auxiliary therapeutic effect of psychological counseling
      treatment after collective rehabilitation training of the patients with anxiety
      disorder. METHODS: 38 college students with anxiety disorder are randomly divided
      into an experiment group and a control group, each of which consists of 19
      students. The experiment group only receives psychological counseling treatment;
      the control group, based on psychological counseling treatment, receives the
      collective rehabilitation training, that is, the joint therapy. RESULTS: before
      the treatment, the inter-group difference of the general data about the patients
      in 2 groups shows no statistically significance, P > 0.05, which is comparable;
      after 8 weeks' treatment, HAMA and SAS scores of the patients in 2 groups are
      significantly improved compared with those before treatment, P < 0.05; meanwhile,
      the improvement effect of the experiment group is better than that of the control
      group P < 0.05. After 3 months' follow-up, it is found that the recurrence rate
      of the experiment group is obviously lower than that of the control group P <
      0.05. CONCLUSION: the joint treatment, consisting of psychological counseling and
      collective rehabilitation training, exercises synergetic effect on the college
      students who are anxiety disorder patients and its curative effect is obviously
      superior to the single psychological counseling and its recurrence rate is low.

PMID- 26309682
TI  - Comparison of three ventilatory modes during one-lung ventilation in elderly
      patients.
AB  - OBJECTIVE: The purpose of this study was to explore the effects of three
      different ventilatory modes: volume controlled ventilation (VCV), pressure
      controlled ventilation (PCV) and pressure controlled ventilation-volume
      guaranteed (PCV-VG) on arterial oxygenation and airway pressure during one-lung
      ventilation (OLV) in elderly patients. METHODS: We enrolled 66 patients who
      underwent thoracic surgery requiring at least 1 hour of OLV and aged above 65
      years into the study. Patients were classified into VCV, PCV and PCV-VG groups
      according to a controlled, randomized design. Patients were ventilated to obtain
      a tidal volume (TV) of 8 mL/kg with three different ventilatory modes during OLV.
      The Hemodynamic and respiratory data had been recorded during intraoperation and
      arterial blood gases were obtained at baseline, 20, 40, 60 minutes after OLV, end
      of surgery. RESULTS: Compared with VCV group, Ppeak was significantly lower in
      PCV and PCV-VG group (P<0.05), and the difference was not found between the PCV
      and PCV-VG group. PaO2 in PCV and PCV-VG group were higher than VCV group after
      the point of OLV+40 (P<0.05). Comparison of PCV group, PaO2 in PCV-VG group was
      higher, but did not show a significantly improved during OLV (P>0.05).
      CONCLUSIONS: Compared with VCV, the use of PCV and PCV-VG have a significant
      advantage in intraoperative oxygenation and airway pressure for eldly patients
      undergoing OLV.

PMID- 26309683
TI  - The assesment of follicular fluid presepsin levels in poor ovarian responder
      womenandits relationship with the reproductive outcomes.
AB  - A considerable proportion of all women undergoing IVFrespond poorly to
      gonadotropin stimulation. These women are reported to be associated with
      increased cancellation rates and lower pregnancy rates. It has been hypothesized
      that poor response to ovarian stimulation is a first sign of ovarian ageing or
      premature ovarian failure, which might be related to altered inflammatory
      response in the body. We aimed to compare follicular fluid presepsin levels
      between poor- and normo-responder patients to ovarian stimulation, to assess its
      relationship with reproductive outcomes. This study included infertility patients
      who underwent ovulation induction with either long GnRH agonist or GnRH
      antagonist protocols and who subsequently underwent IVF/ICSI. Included patients
      were assigned to two groups according to the Bologna criteria for poor ovarian
      response. Group 1 and 2 consisted of normo- and poor-responder patients,
      respectively.The 2 groups were compared in terms of FF presepsin levels. Also,
      any relationship between the FF presepsin levels and fertility outcomes was
      assessed within the groups. The groups were compared by using student's t-test,
      Mann-Whitney U test and X(2) test, where appropriate. Pregnancy rates were not
      significantly different between the groups (22.6% and 17.6%; P=0.650,
      respectively). FF presepsin levels were higher in Group 1, however, the
      difference was not statistically significant (298.0+/-797.4 and 149.2+/-422.3;
      P=0.190, respectively). FF presepsin levels did not significantly differ between
      pregnancy positive and the pregnancy negative patients in both Group 1 (243.6+/
      531.1 and 314.3+/-866.5; P=0.055, respectively) and Group 2 (112.2+/-79.8 and
      157.1+/-464.3; P=0.394, respectively). Consequently, FF presepsin seems not to be
      a reliable marker in predicting pregnancy in both normo-responder and poor
      responder infertility groups. 

PMID- 26309684
TI  - Comparison of early-term effects between totally laparoscopic distal gastrectomy
      with delta-shaped anastomosis and conventional laparoscopic-assisted distal
      gastrectomy: a retrospective study.
AB  - OBJECTIVE: To compare early-term effects of totally laparoscopic distal
      gastrectomy with delta-shaped anastomosis (D-STLDG) with conventional
      laparoscopic-assisted distal gastrectomy (LADG). METHODS: Clinical data of 24
      patients who received D-STLDG from April 2013 to April 2014, and 45 patients who
      received LADG from March 2010 to December 2012 were retrospectively analyzed. The
      operative time, intra-operative blood loss, post-operative recovery time of
      intestinal function, post-operative pain, the length of post-operative hospital
      stay and the incidence of post-operative complications (infection, obstruction
      and delayed gastric emptying) were compared between the two groups. RESULTS: All
      procedures were completed successfully and all patients of both groups were
      discharged smoothly from hospital. Compared with LADG, D-STLDG had shorter
      operative time (175.3+/-64.7 min vs. 205.8+/-42.2 min, P<0.05), less intra
      operative blood (50.8+/-25.3 ml vs. 75.2+/-22.5 ml, P<0.05), shorter post
      operative recovery time of intestinal function (1.2+/-0.5 d vs. 2.1+/-0.8 d,
      P<0.05), less post-operative pain (5.6+/-0.7 vs. 7.8+/-0.5, P<0.05), shorter post
      operative hospital stay (8.5+/-2.2 d vs. 10.5+/-3.5 d, P<0.05). There were no
      significant difference in surgical margins achieved, the number of lymph nodes
      retrieved or the incidence of post-operative complications (infection,
      obstruction and delayed gastric emptying) (P>0.05). CONCLUSION: The delta-shaped
      anastomosis of reconstructing the digestive tract in TLDG appears to be safe,
      feasible and associated to faster recovery.

PMID- 26309685
TI  - Application of continuous renal replacement therapy for acute kidney injury in
      elderly patients.
AB  - This study aims to analyze the factors that affect the prognosis of continuous
      renal replacement therapy (CRRT) in elderly patients with acute kidney injury
      (AKI). Data obtained from 41 elderly patients with AKI who underwent CRRT in our
      department between January 2001 and December 2010 was retrospectively evaluated
      in this study. The enrolled patients were 80 to 100 years old, with a mortality
      of 60.98%. The mean Acute Physiology and Chronic Health Evaluation II (APACHE II)
      score was 27.8+/-5.6 points, and the mean risk coefficient was 0.80+/-0.10. The
      APACHE II score of the survival group was significantly higher than that of the
      death group. The comparisons of therapeutic dosages between <25 mL/(kg?h) and 25
      50 mL/(kg?h), and between 25-50 mL/(kg?h) and >50 mL/(kg?h) all had no
      statistical significance. The prognosis of CRRT and the number of involved organs
      were related to the APACHE II score. Logistic regression analysis revealed that
      the number of involved organ, APACHE II score, mechanical ventilation, and
      hypoalbuminemia were the major risk coefficients that affected the prognosis of
      patients with bedside hemofiltration. The turnover of elderly CRRT patients was
      related to the number of involved organs, APACHE II score, mechanical
      ventilation, hypoalbuminemia, and other factors. The APACHE II score was the
      important reference index of CRRT starting time and could predict mortality risk.

PMID- 26309686
TI  - Different preoperative approaches for acute lumber spinal fractures.
AB  - To compare the long and short term effectiveness of different preoperative
      approaches for lumber spinal fractures and finds a better surgical method for the
      disease. Follow up records of 144 patients received hyperbaric oxygen therapy or
      methylprednisolone infusion within 8 hours after the lubmer spinal injury were
      analyzed. Postoperative outcome immediately and 3, 6, 12, 36 months after the
      surgery were compared to evaluate the effectiveness two different approaches. The
      results indicated that there are no significant differences regarding age, sexual
      proportion, body mass index (BMI), visual analogue scale of pain (VAS) score as
      well as Frankel scores before the surgery, and significant differences VAS score
      as well as Frankel scores immediately after the surgery. In conclusion,
      hyperbaric oxygen therapy within 8 hours after the injury can be more effective
      than methylprednisolone infusion in patients with lumber spinal injury. 

PMID- 26309687
TI  - Surgical approaches to treating otitis media in the only hearing ear of patients
      with contralateral hearing loss.
AB  - The aim of this study was to retrospectively analyze the surgical procedures used
      to treat the only hearing ears of two patient cohorts diagnosed with otitis media
      in the last twenty years. Clinical, surgical, and follow-up data of 15 patients
      with otitis media in the only hearing ear who underwent middle ear surgery prior
      to 2000 (Cohort A) and 13 patients with a similar condition (Cohort B) who
      underwent middle ear surgery between 2000 and 2013 were retrospectively
      collected, analyzed, and compared. Mean preoperative air conduction (AC) and bone
      conduction of the patients in Cohort B was 61 +/- 18.7 and 20 +/- 15.7 dBHL,
      respectively. Mean preoperative and postoperative air bone gap was 43.21 +/- 13.2
      dBHL and 12.66 +/- 3.93 dBHL, respectively. The success rate of the surgical
      procedures in this patient cohort was 85%. Surgery of the only hearing ear in
      patients with otitis media is safe and effective if performed carefully. 

PMID- 26309688
TI  - Cyclin D1 G870A polymorphism and glioma risk in a Chinese population.
AB  - BACKGROUND: A number of studies have suggested that the Cyclin D1 (CCND1) G870A
      polymorphism was associated with susceptibility to various cancers. In the
      present study, we aimed to investigate the association between CCND1 G870A
      polymorphism and the risk of glioma in a Chinese population. MATERIALS AND
      METHODS: CCND1 genotyping was determined by the PCR-RFLP method. The chi (2) test
      was used to assess for any deviation of the genotype frequencies from Hardy
      Weinberg equilibrium and to compare the genotype distributions among glioma
      patients and healthy control subjects. We calculated the odds ratios (ORs) and
      95% confidence intervals (95% CIs) by using unconditional logistic regression.
      RESULTS: The A allele frequency was higher in cases than that in controls (49.40%
      vs. 36.39%), and this difference was statistically significant (P = 0.001). Using
      the G allele as the reference allele, the subjects carrying the A allele had
      3.926-fold increase in the risk of glioma (95% CI, 2.172-7.889), and p-value was
      significant (P = 0.007). Compared to individuals with the GG genotype,
      individuals with the AA genotype exhibited significantly increased glioma risk
      (OR = 3.661, 95% CI: 1.658-6.287, P = 0.01). CONCLUSION: Our results suggest that
      the CCND1 G870A polymorphism may contribute to the susceptibility to glioma in
      Chinese population.

PMID- 26309689
TI  - Probiotic and lactulose: influence on gastrointestinal flora and pH value in
      minimal hepatic encephalopathy rats.
AB  - AIM: The present study was conducted to investigate the influence on
      gastrointestinal flora, counts of bifidobacteria and Enterobacterceae in colon
      and pH value of gastrointestinal after lactulose and probiotic treatment on rat
      experimental minimal hepatic encephalopathy (MHE) induced by thioactamide (TAA).
      METHODS: MHE was induced by intraperitoneal injection of TAA. 48 male MHE models
      were then randomly divided into 4 groups: control group (n = 12); MHE group (n =
      12) received tap water ad libitum only; lactulose group (n = 12) and probiotics
      group (n = 12) gavaged respectively with 8 ml/kg of lactulose and 1.5 g/kg of
      probiotic preparation Golden Bifid (highly concentrated combination probiotic)
      dissolved in 2 ml of normal saline, once a day for 8 days. The latency of
      Brainstem auditory evoked potentials (BAEP) I was used as objective index of MHE.
      Counts of gastrointestinal flora, counts of bifidobacteria and Enterobacterceae
      in colon and pH value of gastrointestinal were examined respectively. RESULTS:
      Compared to MHE group, counts of gastrointestinal flora has greatly decreased,
      ratio of bifidobacteria and Enterobacterceae has greatly increased, pH value of
      colon has greatly descended (P < 0.05). However, there was no significant
      difference between lactulose group and probiotic group (P > 0.05). Both lactulose
      and probiotics can effectively prevent bacteria translocation and overgrowth,
      intensify CR, improved value of B/E, and acidify intestinal, decreased pH value
      of colon. CONCLUSION: Probiotic compound Golden Bifid is as useful as lactulose
      for the prevention and treatment of MHE. Probiotic therapy may be a safe,
      natural, well-tolerated therapy appropriate for the long-term treatment of MHE.

PMID- 26309690
TI  - Diagnosis and treatment of intestinal intussusception in adults: a rare
      experience for surgeons.
AB  - AIM: We evaluated the aetiological factors, diagnoses and treatment outcomes of
      adult cases of invagination of the intestine, or intussusception. We elucidated
      the role of ultrasonography (USG), computed tomography (CT) and other techniques
      in the diagnosis of such cases. PATIENTS AND METHODS: Six patients with
      sufficient medical data, all of whom were followed-up and treated for
      intussusception at Safa Hospital, General Surgery Clinic, Istanbul, Turkey,
      between July 2008 and December 2013, were enrolled. RESULTS: The site of
      intussusception was the small bowel in five cases. The aetiopathology was benign
      in 5 (83.3%) cases and included inflammatory fibroid polyp (IFP) and adhesion.
      The malignant case was adenocarcinoma. The bowel segments involved were ileoileal
      in five cases and ileocolic in one case. CONCLUSIONS: USG and CT aided with the
      diagnosis. Although more rare in adults than in children, cases of ileus
      presenting with acute abdominal disorder, particularly those with an uncertain
      diagnosis, should be considered possible intussusception cases.

PMID- 26309691
TI  - Comparison of early postoperative period electrophysiological and clinical
      findings following carpal tunnel syndrome: is EMG necessary?
AB  - BACKGROUND: In this study, we aimed to compare the clinical findings and ENMG
      results of the patients who underwent surgery due to CTS, in the preoperative and
      early postoperative period. METHODS: 33 wrists of 29 patients who underwent open
      carpal tunnel surgery in our clinic due to CTS, between 2009 and 2011, were
      evaluated. Electrophysiological progress was evaluated with ENMG and clinical
      state with Boston scale. RESULTS: A significant decrease was observed in the
      postoperative BS symptomatic (SSS) and functional (FSS) scores of patients as
      compared to preoperative period (P=0.00), In the electrophysiological findings,
      statistically significant improvement was observed in all groups but very severe
      CTS group (P<0.05). When preoperative and postoperative EMG findings were
      compared, changes in DSL and DSA values were statistically significant (P<0.05).
      However, no statistically significant difference was seen between DML (P=0.085)
      and DMA (P=246) values on the 3rd month. When an examination was conducted on the
      patients whose DML and DSL values could not be obtained in the preoperative EMG,
      DML values were obtained in the early postoperative period in 6 of 7 cases
      (85.71% P<0.001), and DSL values were obtained in 17 of 24 cases (70.8% P<0.000).
      CONCLUSIONS: Sensory nerve findings were more significant, showed faster recovery
      compared to motor nerve findings, and accompanied the clinical recovery.
      Performance of an EMG test, especially on sensory nerves, will be more effective
      in patients selected in the early period, with the exception of patients with
      very severe CTS.

PMID- 26309692
TI  - Laparoscopic versus open inguinal hernia repair on patients over 75 years of age.
AB  - AIM: In this prospective study, we aimed at comparing the laparoscopic and
      conventional open inguinal hernia repair procedures in the population over 75
      years of age. MATERIALS AND METHODS: The medical data of 108 patients over 75
      years of age who presented with inguinal hernia and underwent surgical treatment
      between July 2008 and December 2012 in Safa Hospital, General Surgery Department
      were prospectively recorded. RESULTS: The mean age of patients in the open
      procedure group (n=75) and in the laparoscopic group (n=33) was 82 and 81 years,
      respectively. The mean American Society of Anaesthesiologists score was 2-7 in
      the open group and 2-4 in the laparoscopic group (P<0.005). There was no
      statistically significant difference between the groups with respect to
      perioperative complications. There was no mortality. CONCLUSION: Similar to the
      outcome of open procedure, laparoscopic inguinal hernia repair can safely be
      performed without an increase in morbidity and mortality in the advanced age
      population.

PMID- 26309693
TI  - Effect of edaravone on serum SP-A and arterial blood gas in patients with
      lobectomy.
AB  - OBJECTIVE: To discuss the effect of edaravone on serum pulmonary surfactant
      protein A (SP-A) and arterial blood gas (ABG) in patients with thoracoscopic
      lobectomy. METHODS: 40 lung cancer patients with right side of lobectomy were
      randomly divided into control group (group C, 20 cases) and edaravone group
      (group E, 20 cases). Group E was treated edaravone (1 mg/kg) between induction
      and skin incision, dropping within 30 min; group C was treated with equivalent
      normal saline. The venous and arterial blood were collected in both groups
      immediately before incision (T0), after 1 h of one-lung ventilation 1 h (T1) and
      in 1 h after lungs ventilation (T2) for ABG analysis and measurement of serum SP
      A level. Results After OLV, serum SP-A levels were significantly increased in
      both groups (P < 0.05); compared with group C, serum levels of SP-A were reduced
      (P < 0.05) and ABG was significantly improved in group E. CONCLUSION: Edaravone
      can reduce serum SP-A levels in patients with lobectomy and alleviate acute lung
      injury to a certain extent in surgery.

PMID- 26309694
TI  - Association between XRCC1 Arg399Gln polymorphism and glioma risk in a Chinese
      population: a case-control study.
AB  - AIM: In China, the incidence rates of glioma tend to be increased, however, the
      genetic contribution to its etiology is not well-understood. The aim of this
      study is to evaluate the association of XRCC1 Arg399Gln polymorphism with glioma
      risk in a Chinese population. MATERIALS AND METHODS: We conducted a case-control
      study on 387 patients with glioma and 400 cancer-free controls between 2004 and
      2014. Peripheral blood samples of both groups were processed for DNA extraction
      and genotyping of the XRCC1 Arg399Gln polymorphism using PCR-RFLP. Comparison of
      the distribution of Arg399Gln genotypes in the study groups was performed by
      means of 2-sided contingency tables using the chi(2) test. Hazard ratios (HRs)
      were estimated by Cox proportional hazard regression model. RESULTS: When the AA
      genotype was used as the reference group, the GG genotype was associated with
      significantly increased risk for glioma (adjusted OR = 3.18, 95% CI = 1.38-3.88;
      P = 0.017). Under the dominant model of inheritance, the AG + GG genotype was
      associated with significantly increased risk for glioma (adjusted OR =2.33, 95%
      CI = 1.12-5.81; P = 0.023). When the A allele was used as the reference group,
      the G allele was associated with increased glioma risk (adjusted OR, 2.44, 95%
      CI, 1.76-4.18; P = 0.003). CONCLUSION: Our data suggests that XRCC1 Arg399Gln
      polymorphism contribute to increased risk of glioma, which may be susceptibility
      biomarkers for glioma.

PMID- 26309695
TI  - Efficacy investigation of transpostceliac single-port 3-channel laparoscope in
      the treatment of complex renal cyst.
AB  - This study aims to investigate the surgical method and long-term efficacy of
      transpostceliac single-port 3-channel laparoscope in the treatment of complex
      renal cyst. A retrospective analysis was performed towards the 37 patients who
      underwent renal cyst unroofing decompression with single-port laparoscope from
      Jun. 2012 to Jul. 2013. The surgery was performed through the postceliac
      approach, a 2.5 cm incision was made 4-5 cm away from the iliac spine of
      midaxillary line, the Olympus single-port TriPort was then implanted, with the
      laparoscopic channel and the other two operation channels all as 5 mm. The
      operation was completed with the forceps and scissors which had flexible fronts.
      The cysts of the 37 patients were performed the appropriate surgical treatments
      according to their subtype grouping, on case was transferred to the open surgery,
      and there was no blood transfusion case. The operation time was 11-42 min, with
      the mean time as 23 min; the bleeding volume was 10-50 ml, with the mean volume
      as 26 ml; the postoperative follow-up was 1-6 months, and the ultrasound review
      did not find the recurrence of cyst; the postoperative lumbar scar was
      approximately 2.5 cm, and the patients could leave the bed and perform some acts
      on the exact day of the surgery; the hospitalization time was 1-2 d, with the
      average time as 1.2 d. The efficacy of the transpostceliac single-port 3-channel
      laparoscope in the treatment of complex renal cyst was positive, with low
      recurrence rate, and worthy of further promotion. 

PMID- 26309696
TI  - Effect of gene polymorphism of COMT and OPRM1 on the preoperative pain
      sensitivity in patients with cancer.
AB  - OBJECTIVES: To evaluate the effect of COMT and OPRM1 gene polymorphisms on the
      preoperative pain sensitivity in tumor patients. METHODS: 300 cases of cancer
      patients undergoing elective surgery were included, and the Val158 Met loci of
      COMT gene and OPRM1 loci of A118 G gene were genotyped by PCR-RFLP. Pain
      threshold and pain tolerance threshold were measured using electrical stimulation
      to investigate the preoperative pain sensitivity in patients with different
      genotypes. RESULTS: For the COMT gene, the pain threshold and pain tolerance
      threshold of patients with M allele both decreased (both P < 0.001); for PPRM1
      gene, pain threshold and pain tolerance threshold of patients with G allele
      decreased (both P < 0.001). We also found that there was an interaction between
      the two genes. CONCLUSION: Gene polymorphisms of COMT and OPRM1 were correlated
      with the preoperative pain sensitivity of cancer patients. The patients with M
      allele of COMT and G allele of OPRM1 had higher preoperative pain sensitivity.

PMID- 26309697
TI  - Ultrasonographic findings of triple-negative breast cancer.
AB  - OBJECTIVE: Our aim was to determine whether triple-negative breast cancer (TNBC)
      has distinguishing sonographic features compared to non-TNBC. METHODS: Data from
      145 consecutive breast cancer patients were collected. The images were
      reevaluated by two dedicated breast imaging experts according to the Breast
      Imaging Reporting and Data System. The sonographic features of 45 TNBC patients
      were compared with those of 100 non-TNBC patients. RESULTS: TNBC showed a high
      histological tumor grade. On ultrasound, TNBC was more frequently to present as
      oval or round mass shape (48.9%, 17.8%; respectively), more likely to have
      circumscribed margins (82.2%), and less likely to show posterior attenuating
      (8.9%). Additionally, compared with non-TNBC, TNBC was less likely to have
      calcification (35.6%). CONCLUSION: TNBC has distinguishing imaging features on
      breast ultrasound, and more likely to be associated with benign masses. Knowledge
      of the distinct sonographic features would be useful in diagnosing TNBC.

PMID- 26309698
TI  - Cauda equina syndrome caused by isolated spinal extramedullary-intradural cauda
      equina metastasis is the primary symptom of small cell lung cancer: a case report
      and review of the literatrure.
AB  - OBJECTIVES: To describe a case of extramedullary-intradural metastases causing
      cauda equina syndrome (CES) as the primary syndrome of lung cancer, and to review
      the pertinent medical literature. SUMMARY OF BACKGROUND DATA: Intradural spinal
      metastasis is rare, accounting for 6% of all spinal metastases. Of all primary
      lesion types, lung carcinoma is about 40-85%. Extramedullary-intradural
      metastases of lung cancer causing CES is unusual. METHODS: A 55-year-old patient
      with symptoms of low back pain that radiated to bilateral lower legs with painful
      paresthesias and piecemeal sphincter disturbances and lead to urinary
      incontinence, and constipation at last for three months. The MRI showed that
      there was an isolated, well-demarcated, intradural extramedullary mass at the L3,
      4 levels. RESULTS: The patient was admitted to the hospital as the severe cauda
      equina syndrome (CES) and considering the possibility of nerve system neoplasms
      for surgery. After a series of examinations, the X-ray and computed tomography
      (CT) detected a tumor in the left upper lobe with hilar and mediastinal lymph
      node metastases. The concluded diagnosis through histopathologic examination with
      immunohistochemistry after the patient received an L3-L4 laminectomy and tumor
      excision and biopsy was extramedullary-intradural spinal metastasis of the small
      cell lung cancer (SCLC). The patient had a rapid improvement of the CES.
      CONCLUSION: Although the majority of cauda equina tumors are primary tumors,
      extramedullary-intradural metastasis should be considered before surgery in
      patients with rapid developed CES.

PMID- 26309699
TI  - Non-Epstein-Barr virus-associated double primary lymphoepithelioma-like carcinoma
      of the esophagus and stomach: a case report and literature review.
AB  - A 55-year-old Chinese male was admitted to the hospital for epigastralgia and
      dysphagia with a two month history, and hematemesis and melena with a two-day
      history. Two lesions were found in the esophagus and stomach by esophago-
      gastroduodenoscopy and computed tomography. The patient underwent subtotal
      esophagectomy and gastrectomy, esophagogastric anastomosis above the aortic arch,
      and thoracic-abdominal two-field lymph node dissection. Pathological and
      immumohistochemical studies showed that both lesions had the same form of poorly
      differentiated carcinoma with dense lymphoid stroma, which was diagnosed as
      lymphoepithelioma-like carcinoma (LELC). No metastatic relationship was found
      between the two tumors. Therefore, the case was double primary lymphoepithelioma
      like carcinoma of the esophagus and stomach. Epstein-Barr virus (EBV) in the two
      tumors were negative by EBV-encoded small RNA1 (EBER-1) in situ hybridization. No
      adjuvant therapy was performed due to his poor physical condition post
      operatively, and no evidence of tumor recurrence or metastasis was found during
      the next 14 months of follow-up. Esophageal and gastric LELC are rare, especially
      the former, which has a specific geographical distribution. Literature reported
      cases showed upper gastrointestinal LELC were highly malignant with good
      prognosis, and EBV was detected less in esophageal LELC cases but more commonly
      in gastric LELC cases. Upper gastrointestinal LELC lesions are usually singular,
      and no synchronous lesions were reported in the literature. Our case is the first
      LELC to present as double primary lymphoepithelioma- like carcinoma of both
      esophagus and stomach simultaneously, which demonstrates that LELC can be
      multifocal in the upper gastrointestinal tract. 

PMID- 26309700
TI  - Ilizarov bone transport combined with antibiotic cement spacer for infected
      tibial nonunion.
AB  - PURPOSE: To evaluate the curative effect of Ilizarov bone transport combined with
      antibiotic cement spacer for infected tibial nonunion with bone defect. METHODS:
      We retrospectively reviewed the outcomes of 58 patients with infected tibial
      nonunion from January 2008 to March 2011 at our institution. Patients were
      treated with complete debridement, radical sequestrectomy, antibiotic cement
      spacer implantation, bone transport using the Ilizarov external fixator, and soft
      tissue reconstruction. Clinical efficacy was assessed using Paley's grading
      system and patient satisfaction at the last follow-up. RESULTS: Follow-up ranged
      from 24 to 63 months (average, 31.6 months). Mean size of the tibial defect was
      9.2 cm (range, 6-15 cm). The soft tissue defect was closed successfully in all
      cases. Patients eventually achieved union with a mean bone union index of 1.2
      months/cm at an average of 10.6 months (range, 8-31 months). In terms of Paley
      grade, 30 patients had excellent results, 23 good, and 5 fair. Functional results
      were excellent in 28 patients, good in 18, and fair in 12. Thirty-five patients
      felt extremely satisfied, 18 satisfied, and 5 acceptable with the functional
      outcome. Complications included pin site infection in 18 cases, limb length
      discrepancy less than 1.5 cm in 10, knee stiffness in 5, equinus deformity in 4,
      infectious recurrence in 1 and pin breakage in 1. There was no refracture at the
      reconstruction site. CONCLUSION: Ilizarov bone transport combined with antibiotic
      cement spacer is a versatile and effective method for treatment of infected
      tibial nonunion.

PMID- 26309701
TI  - Total elbow joint replacement for the treatment of distal humerus fracture of
      type c in eight elderly patients.
AB  - OBJECTIVE: To analyze the outcomes of total elbow arthroplasty in the treatment
      of elderly type C distal humeral fractures and discuss the clinic efficacy.
      METHODS: 8 cases of elderly type C distal humeral fractures, Male was in one
      case, female in seven cases, and the average age was 66.5 years (60-81). All
      cases were closed fractures because of falling and none had associated injuries.
      According to AO classification, type C1 were in one cases, C2 in four cases and
      C3 in three cases. The average time from injury to operation was 5.5 days (3-9),
      and the type of prosthesis which all cases replaced was Coonrad-Marrey. The
      postoperative follow-up was obtained regularly which the contents included Mayo
      elbow score, pain evaluation, the motion range and the stability of the elbow,
      muscle strength, examination of related complications such as heterotopic
      ossification, prosthesis loosening and nerve damage. RESULTS: The incision
      infection was in one case, ulnar nerve symptom in two cases, weakness of musculus
      triceps brachii in one case and mild pain of elbow in two cases. The average
      motion rage of elbow was 103.5+/-3.2 degree (78-118) in flexion-extension and
      126.4+/-4.1 degree (94-148) in rotation. All elbow joints were stable
      postoperatively, no prosthesis loosening and apparent wear was found. The
      heterotopic ossification was found in 1 case. The average Mayo elbow score was
      85.2+/-3.4 (75-95), four cases of excellent and four cases of good. CONCLUSION:
      The total elbow arthroplasty was recommended in clinic to treat elderly type C
      distal humeral fractures because the clinic outcomes are satisfied.

PMID- 26309702
TI  - Long-term unexpected consequence of two kidney transplants with full-match
      grafts: a report of two cases.
AB  - HLA typing is the cornerstone of kidney transplantation. Here, we present two
      full-match kidney transplants with early uneventful course but late c4d-mediated
      rejection and recurrent pauce-immune necrotizing crescentic glomerulonephritis,
      as each in one. Case 1: A 49 years old Caucasian female patient, received a six
      matched cadaveric kidney and had nonspecific changes in 6th and 12th month
      protocol biopsies. The first and third year serum creatinin value was 1.8 and 2.0
      mg/dl. Immunosuppressive drugs were gradually reduced due to recurrent infections
      at the 3rd year. She admitted with allograft dysfunction and serum creatinin 5.8
      mg/dl. Kidney biopsy of graft dysfunction at the 4th year was diagnosed C4d
      mediated rejection. Case 2: A 61 years old Caucasian female patient received a
      HLA-identical kidney 8.5 years ago from her sibling had a primary vasculitis
      mediated necrotizing crescentic glomerulonephritis. Her serum creatinin values in
      the 1st and 8th years were 1.3 and 1.7 mg/dl. In recent years, immunosuppressive
      dosage has been gradually reduced due to recurrent lower respiratory tract
      infections. She admitted with hematuria, purpuric rash, dyspnea. and serum
      creatinin 5.7 mg/dl. Renal biopsy revealed necrotizing crescentic
      glomerulonephritis. The patient was treated with pulse steroid, double filtration
      plasmapheresis and rituximab. She is being followed with a functioning graft and
      with serum creatinin 2.0 mg/dl. In case of recurrent infection, immunosuppressive
      drugs should be modified cautiously even in patients with full-match grafts to
      prevent late acute rejection or recurrence of the primary disease. 

PMID- 26309703
TI  - Combined laparoscopic and vaginal cervicovaginal reconstruction using split
      thickness skin graft in patients with congenital atresia of cervix.
AB  - OBJECTIVE: The aim of this study was to introduce a new technique which is
      combined laparoscopic and vaginal cervicovaginal reconstruction using split
      thickness skin graft in patients with congenital atresia of cervix and to
      evaluate the feasibility and the safety of it. METHODS: This is a prospective
      observational study of 10 patients with congenital atresia of cervix who
      underwent combined laparoscopic and vaginal cervicovaginal reconstruction using
      split thickness skin graft for cervicovaginal reconstruction from February 2013
      to August 2014 in our hospital. All of the surgical procedures were carried out
      by the same operation team. Patient data were collected including operating time,
      estimated blood loss, hospital stay post-surgery, complications, total cost, and
      median vaginal length at 3 month, resumption of menstruation, vaginal stenosis
      and stricture of the cervix postoperatively. RESULTS: The operative procedure
      lasted 237+/-46 (175-380) min. The estimated blood loss was 160+/-76 (50-300) ml.
      The hospital stay post-surgery was 12+/-2 (9-18) days. None of the patients had
      complications or required a blood transfusion. The mean total cost was $3352+/
      1025. The average vaginal length at 3 month was 8.3+/-1.1 (8-10) cm. All patients
      had resumption of menstruation. The patients were followed for a mean of 5+/-2 (1
      10) months. Cervical or vaginal stenosis did not occur in any of the patients.
      CONCLUSIONS: Our experiences of combined laparoscopic and vaginal cervicovaginal
      reconstruction using split thickness skin graft in10 patients with congenital
      atresia of cervix were positive, with successful results and without
      complications, and cervical or vaginal stenosis.

PMID- 26309704
TI  - Elastic nails for fibular fracture in adult tibiofibular fractures.
AB  - Treatment of adult tibiofibular fractures, especially severely comminuted
      fractures, is technically challenging due to the lack of reduction markers and
      difficulty in restoring the alignment. Fixation of the fibula can facilitate
      reduction of the tibia fracture and restoration of the lower-extremity alignment.
      However, there are few literatures mentioned using intramedullary nail fixation
      for fibular fractures. Twenty-three cases of tibiofibular fractures were treated
      with elastic nails fixation fibular fractures and intramedullary nail or plate
      stabilization tibial fractures between January 2012 and December 2012. Adult
      tibiofibular fractures with fibular neck fractures or fibular fracture line apart
      from the ankle joint surface within 8 cm was ruled out. There were 19 males and 4
      females with an average age of 41 years (range, 21-59 years). The injury causes
      included 11 falls and 12 traffic accidents. The left side was involved in 11
      cases and the right side was involved in 12 cases. Seventeen cases were closed
      fractures and 6 cases were open fractures, all were Gustilo type I and II
      fractures. According to the AO classification, six fractures were defined as type
      42A, 11 as type 42B, and 6 as type 42C. The average interval between injury and
      surgery was 5.8 d (range, 3-22 d). The operation time of elastic nails fixation
      fibular fractures was 24 minutes (range, 15-42 minutes). Primary wound healing
      was achieved in all patients. No complications such as infection and wound
      necrosis occurred. Twenty-one patients were followed up for a mean follow-up
      period of 16.3 months (range, 12-26 months). The mean duration of fracture
      healing in the radiographs was 4.1 months (range, 3-8 months). No recurrent
      fracture dislocation and breakage of implant were observed. At the last follow-up
      visit, the lower-extremity alignment was excellent. Two degrees of varus
      deformity was found in 3 cases, and 2 degrees of valgus deformity was observed in
      2 cases, but there were no serious varus or valgus deformity affecting the lower
      extremity function or causing pain. The results of Tornetta's ankle function
      scoring were excellent in 17 cases, good in 3 cases, and fair in 1 case; and the
      good-to-excellent rate was 95.2%. In the case of adult tibiofibular fractures,
      elastic nails fixed fibular fracture is helpful to maintain and adjust the lower
      limbs axis, help tibial fracture reduction, and increase stability. 

PMID- 26309705
TI  - Primary non-hodgkin lymphoma of lateral skull base mimicking a trigeminal
      schwannoma: case report.
AB  - Primary extranodal lymphoma is a common malignant tumor of head and neck but
      rarely presents in lateral skull base. We reported such a case of lymphoma
      categorized as diffuse large B-cell lymphoma (DLBCL) subtype in a 74-year-old
      Chinese female. She has experienced an acute course of continuously trigeminal
      neuralgia and Horner's syndrome. The lesion was diagnosed as trigeminal
      schwannoma based on symptom and medical image before operation then confirmed to
      be DLBCL pathologically. 

PMID- 26309706
TI  - A novel factor X gene mutation Val (GTC) 384Ala (GCC) in a Chinese family
      resulting in congenital factor X deficiency.
AB  - FX is a vitamin K-dependent coagulation protease critically essential for the
      coagulation cascade. FXD (congenital deficiency of factor X) is a rare
      coagulation disorder that inherited as an autosomal recessive trait. Here we
      reported a patient with bleeding diathesis from infant. The proband with
      pseudotumor in cerebral articular and cavity were identified as encapsulated
      hematocele ultimately. FX sequence analysis revealed that the patient carried a
      novel homozygous missense mutation that resulted in the Val384Ala substitution.
      Further investigation of the novel mutation would deepen our understanding of the
      bleeding mechanism involved in FXD. 

PMID- 26309707
TI  - Clinical and laboratory observation of Bacillus Calmette-Guerin infections.
AB  - OBJECTIVE: To study the clinical features of BCG infection in children. METHODS:
      51 cases confirmed with BCG infection from all over China were enrolled and
      followed up for at least 6 months. All cases were treated with anti-tuberculosis
      drugs. A random, open, group control study was designed in non-disseminated cases
      to evaluate curative effects of anti-tuberculosis drugs for early stage BCG
      infection. Disseminated cases were also closely monitored, and patients were
      given combined anti-tuberculosis drug therapy. RESULTS: In 34 (66.7%) non
      disseminated cases, 19 children with local infections were treated with Isoniazid
      (Group A) and 15 were treated with Isoniazid and Rifampin (Group B). In the first
      3 months, Group B responded better to anti- tuberculosis drug therapy than Group
      A (P<0.05). At the end of 6 months drug therapy, improvement rate was 100% of
      Group B vs. 89.5% of Group A (P<0.05). 33.3% children were admitted with
      disseminated BCG disease and were initially treated with Isoniazid and Rifampin.
      Most of these children responded poorly to drug therapies: Both isolated strains
      and BCG vaccination strain showed resistance to isoniazid, but susceptible to
      other First-line anti-tuberculosis drugs (Rifampin, Ethambutol and Streptomycin).
      CONCLUSION: INH does not perform well for treating BCG Chinese infections.
      Multiple drug regimens are necessary for treatment and preventing Drug
      Resistance. Even for non-disseminated cases, preventive therapy using mono
      isoniazid regimen is not suitable. BCG infections also occur in children without
      clear immunodeficiency, so parental education and awareness of health-care
      workers is essential for promptly recognition and handling BCG infections.

PMID- 26309708
TI  - Rapid evolving into acute myeloid leukemia in a patient with multiple myeloma and
      concurrent myelodysplasia after VTD therapy.
AB  - The association of Myelodysplasia (MDS) and multiple myeloma (MM) has been
      usually described not only as a complication of chemotherapy but also in the
      absence of preceding chemotherapy or together at the time of diagnosis. Optimal
      therapies of a coexisting MM and MDS have not been well established up to now. We
      report a case of MDS diagnosed simultaneously with MM. After treatment with VTD
      (bortezomib, thalidomide, dexamethasone) marked anti-myeloma activity was
      observed, but it was associated with rapid progression of the MDS to acute
      myeloid leukemia (AML). The leukemic transformation in our case most probably
      reflects the natural progression of MDS, though it clearly demonstrates that VTD
      is ineffective in controlling blast proliferation in MDS. To our knowledge, this
      is the first case report on MDS in the setting of MM with rapid evolution to AML
      to VTD therapy. More data from more cases are needed, to find the potential
      utility of VTD therapy in coexisting MDS and MM patients. 

PMID- 26309709
TI  - -374T/A polymorphism of the receptor for advanced glycation end products is
      associated with decreased risk of breast cancer in a Chinese population.
AB  - PURPOSE: we aimed to investigate the receptor for advanced glycation end products
      (RAGE) -374T/A polymorphism and breast cancer risk in a Chinese population.
      METHODS: The study subjects included 188 women with histologically confirmed
      breast cancer and 210 controls. The RAGE genotypes were determined using
      Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP)
      assay. Pearson's chi(2) test was used to test the association between cases and
      controls and genotype frequencies. The association between the polymorphism and
      risk of breast cancer was estimated by odds ratio (OR) and 95% confidence
      interval (95% CI). RESULTS: The AA genotype was significantly higher in breast
      cancer patients than in controls (37.77% vs. 28.10%, P = 0.002). Furthermore, the
      A allele frequency was significantly higher in the case group than in the control
      group (55.32% vs. 42.14%, P < 0.001). With the TT genotype as reference, the
      adjusted OR for AA homozygous carriers reached to 0.36 (95% CI: 0.17-0.88; P =
      0.03). Under the dominant model of inheritance, the TA+AA genotype was associated
      with significantly decreased risk for breast cancer (adjusted OR = 0.38, 95% CI =
      0.27-0.87; P = 0.02). The A allele carriage also presented a lower risk for
      breast cancer (adjusted OR = 0.42; 95% CI, 0.33-0.91; P = 0.04). CONCLUSION: Our
      findings suggest that the polymorphic variants of RAGE-374T/A may have an
      influence on breast cancer risk among Chinese women.

PMID- 26309710
TI  - Is non-thyroidal illness syndrome a predictor for prolonged weaning in intubated
      chronic obstructive pulmonary disease patients?
AB  - INTRODUCTION: Non-thyroidal illness syndrome (NTIS) is considered to be
      associated with adverse outcomes in intensive care unit (ICU) patients. In this
      study, we evaluated the association between NTIS and prolonged weaning in chronic
      obstructive pulmonary disease (COPD) patients admitted to the ICU. MATERIALS AND
      METHODS: In total, 125 patients with COPD admitted to our ICU who underwent
      invasive mechanical ventilation (MV) were enrolled. We collected each patient's
      baseline characteristics including Acute Physiology and Chronic Health Evaluation
      (APACHE) II score, body mass index (BMI), and thyroid hormones 24 h after ICU
      admission. The presence of pulmonary infection was also recorded. The primary
      outcome was prolonged weaning, defined as patients who failed at least three
      weaning attempts or required > 7 days of weaning after the first spontaneous
      breathing trial. RESULTS: Of the 127 patients studied, 64 had normal thyroid
      function tests and 61 had NTIS. Patients with NTIS had significantly higher
      APACHE II scores, prolonged weaning, and pulmonary infection. Patients with NTIS
      had a higher risk for prolonged weaning (odds ratio, OR = 3.21; 95% CI = 1.31
      7.83).The presence of pulmonary infection was also an independent risk factors
      for prolonged weaning. CONCLUSIONS: NTIS may be an independent predictor for
      prolonged weaning in intubated COPD patients.

PMID- 26309711
TI  - Synthesis and evaluation of perfluorooctylbromide nanoparticles modified with a
      folate receptor for targeting ovarian cancer: in vitro and in vivo experiments.
AB  - BACKGROUND: Epithelial ovarian cancer is the leading cause of death among
      gynecologic malignancies. However, detecting ovarian cancer at an early stage
      remains challenging. In this work, we aimed to synthesize a folate-receptor
      targeting perfluorooctylbromide nanoparticle (FR-TPNP) as a targeted computed
      tomography (CT) contrast agent for the early detection of ovarian cancer.
      METHODS: Perfluorooctylbromide (PFOB) was encapsulated in Poly (lactic-co
      glycolic acid) (PLGA) by a two-step emulsion technique to construct the
      nanoparticles. Folate-poly (ethylene glycol)-carboxylic acid (Fol-PEG-COOH) was
      introduced to modify the surface of the nanoparticles through attachment to the
      PLGA. The effects of different volume ratios of PFOB to PLGA on the
      characteristics of the FR-TPNP emulsions were compared. The size distribution and
      potential of the FR-TPNPs were assessed with a laser particle size analyzer
      system. The in vitro targeting ability of the FR-TPNPs was observed with a
      confocal laser scanning microscope (CLSM), and the in vivo transportation of the
      FR-TPNPs was evaluated with CT. RESULTS: The sizes of the FR-TPNP emulsion with
      different volume ratios varied from 302.67 +/- 27.83 nm to 563.68 +/- 47.29 nm,
      and the mean CT value ranged from 233 +/- 20.59 HU to 587.66 +/- 159.51 HU. Both
      the size and mean CT value increased with the volume ratio. The FR-TPNPs showed
      greater cell affinity and targeting efficiency to SKOV3 cells than the control
      group and folic acid interference group in vitro, as observed by CLSM. A
      significant CT enhancement of ovarian cancer xenografts in the targeted group of
      a nude mice model was observed 2 h post-injection; it increased to a peak at 12 h
      and had a duration of 48 h. The mean CT value of the tumor in the targeted group
      was considerably higher than those in the non-targeted and other groups 6 h post
      injection. CONCLUSION: The synthesized FR-TPNP emulsion was an effective CT
      contrast agent with highly efficient targeting ability and a long circulation
      time, thus representing a potential strategy for the earlier detection of ovarian
      cancer.

PMID- 26309712
TI  - Puerarin inhibits proliferation and induces apoptosis in human glioblastoma cell
      lines.
AB  - Puerarin has been widely used in clinical treatment and experiment research and
      is considered to exert an anticancer effect recently. The present study
      investigated the anticancer activity of puerarin in U251 and U87 human
      glioblastoma cells. The cells were treated with puerarin at various
      concentrations for different times. Cell viability and cell proliferation were
      detected by cell counting kit-8 (CCK-8) assay and 5-ethynyl-2'-deoxyuridine (EdU)
      staining respectively. Cell cycle and apoptosis were measured separately with PI
      staining and Annexin V-FITC/PI double staining method by flow cytometry. DNA
      damage of glioblastoma cells caused by puerarin exposure was evaluated by gamma
      H2AX foci detection, and the expressions of p-AKT, caspase-3 and apoptosis
      related proteins were detected by Western blotting after puerarin treatment. Cell
      viability and proliferation of glioblastoma cells treated with puerarin were
      significantly lower than that of the control group; the apoptosis rate increased
      obviously compared to the control group. Puerarin significantly decreased the
      proportion at G1 phase of cell cycling accompanied by increased populations at
      the S and G2/M phases in both cell lines. At the same time, DNA damage level of
      puerarin treated cells was significantly higher than that in the control cells.
      Moreover, puerarin treatment suppressed the expression of p-Akt and Bcl-2 and
      promoted the expression of Bax and cleaved caspase-3 in U251 cells. These
      findings indicate that puerarin exerts antitumor effects both in U251 and U87
      cells. 

PMID- 26309713
TI  - Quantitation of nuclear factor kappa B activation in pancreatic acinar cells
      during rat acute pancreatitis by flow cytometry.
AB  - This study aimed to develop a specific and sensitive method for the rapid
      detection of NF-kappaB activity in pancreatic tissue. Male Wistar rats were
      randomly divided into two groups: (1) 16 rats in the acute pancreatitis (AP)
      group received retrograde injection of 5% sodium taurocholate (STC) into the
      biliopancreatic duct, and (2) 16 rats in the Control group received saline. NF
      kappaB activation in rat pancreatic acinar cells was assessed by flow cytometry
      (FCM). We found that the NF-kappaB activity in the AP group significantly
      increased at 1.5 h (29.80%+/-7.83), had a peak at 3 h (65.17%+/-13.22), and then
      decreased gradually to 12 h time point, close to the level after 1.5 h
      stimulation of STC. The NF-kappaB activity of the Control group did not
      significantly vary at different time points (P>0.05). FCM is a specific and
      sensitive assay for the rapid detection of NF-kappaB activity in pancreatic
      tissue. 

PMID- 26309714
TI  - A comparison analysis of Listeria monocytogenes isolates recovered from chicken
      carcasses and human by using RAPD PCR.
AB  - Chicken meat is a valuable source of protein and consumption of it continues to
      rise day to day. The aim of the present study was to evaluate the genetic
      homogeneity of Listeria monocytogenes (L. monocytogenes) isolates obtained from
      chicken carcasses and human. Random Amplification of Polymorphic DNA (RAPD) PCR
      with three different primers were used to analyze the 31 L. monocytogenes
      isolates recovered from human and chicken carcasses. Primers were D8635, HLWL74,
      and OPM01. Scanned images of RAPD-PCR products were analyzed using Photocap
      software. The data were analyzed by SPSS software using Jaccard distance matrix
      and Ward's hierarchical cluster technique, isolates were clustered and displayed
      in dendrogram form. Molecular serotyping of the isolate was done. Most of the
      isolates were grouped into two serogroup IIb and IIa. However some of them were
      serotyped as IVb serogroup. In the RAPD assay, all of the primers gave amplified
      bands. Among these three primers, OPM01 had the most discriminatory power due to
      producing polymorph bands. Totally, 75 different bands with sizes ranging from
      150 bp to 3300 bp, were produced. The dendrogram for Listeria monocytogenes
      isolates from chicken and human showed five different clusters (designed as A to
      E). In this study, there wasn't any association between food and human isolates
      of L. monocytogenes. RAPD has more discriminatory power than serotyping. On the
      other hand, there were different RAPD profiles among isolates of the same
      serotype and also, similar RAPD profile among different serotypes were observed. 

PMID- 26309715
TI  - The association between IGF-1 polymorphisms and high myopia.
AB  - BACKGROUND: The potential association between IGF-1 polymorphisms and high myopia
      has been investigated in previous studies, but the actual relationship remains
      controversial. Accordingly, we conducted a meta-analysisincludingcase-control and
      cohort studies to assess the existing relationship between high myopia and IGF-1
      polymorphisms. We searched MEDLINE, EMBASE, and OVID. Odds ratios (OR) with 95%
      confidence intervals (CI) were derived for single-nucleotide polymorphisms (SNPs)
      involved in the studies obtained from the retrospective database search. Analyses
      of heterogeneity, sensitivity, and publication bias were also conducted. The
      findings from this meta-analysis were based on approximately 2,187 high myopia
      cases and 1,183 controls, and were used to assess the association between three
      IGF-1 genetic polymorphisms (rs6214, rs12423791, and rs5742632) and high myopia
      risks. We investigated the association of the IGF-1 gene SNP rs6214, but no
      statistical association was observed in the resulting odds ratios (OR) in the
      allelic (OR = 1.06, 95% CI = 0.89-1.25), dominant (OR = 1.07, 95% CI = 0.90
      1.27), or recessive models (OR = 1.06, 95% CI = 0.89-1.26), or in the homozygote
      (OR = 1.12, 95% CI = 0.91-1.38) and heterozygote comparisons (OR = 1.06, 95% CI =
      0.88-1.27). Simultaneously, two other selected SNPs, rs12423791 and rs5742632,
      were also studied, but similarly, no statistical association existed between
      these polymorphisms and the risk of high myopia. In conclusions, no statistical
      association between IGF-1 polymorphisms (rs6214, rs12423791, and rs5742632) and
      the risk of high myopia was observed following the reported meta-analysis.

PMID- 26309716
TI  - K-ras genetic mutation and influencing factor analysis for Han and Uygur
      nationality colorectal cancer patients.
AB  - To investigate the K-ras genetic mutation status in colorectal cancer patients,
      compare the difference of K-ras genetic mutation rate in Han and Uygur
      nationality and analyze the influencing factor. 91 cases (52 cases of Han
      nationality and 39 cases of Uygur nationality) of colorectal biopsy or surgical
      ablation pathology specimen from the first affiliated hospital of Xinjiang
      Medical University during January, 2010 to March, 2013 were collected to detect
      the 12th and 13th code mutation status of K-ras gene exon 2 with pyrosequencing
      method and compare the difference of K-ras gene mutation rate between Han and
      Uygur nationality patients. Single factor analysis and multiple factor logistic
      regression analysis were utilized to analyze the influencing factor for K-ras
      genetic mutation. 33 cases of patients with K-ras genetic mutation were found
      from the 91 cases colorectal cancer patients and the total mutation rate was
      36.3%. Among them, 24 cases (72.7%) were found with mutation only in the 12th
      code, 9 cases (27.3%) were found with mutation only in the 13th code and no one
      case was found with mutation in both the two codes. Mutation rate of the 12th
      code in the Uygur nationality was significantly higher than that in the Han
      nationality (P<0.05), but there were no significant difference in the comparison
      of the total mutation rate and the 13th code mutation rate between the two groups
      (P>0.05). There were no associativity (P>0.05) between the K-ras genetic mutation
      and sex, age, smoking history, drinking history, tumor location, macropathology
      type, differentiation level, staging, invasive depth, lymph nodes transferring
      and metastasis in colorectal cancer patients (P>0.05). K-ras genetic mutation
      rate is high in colorectal cancer patients. The mutation rate of 12th code in
      Uygur nationality is higher than that in Han nationality. There is no significant
      associativity between K-ras genetic mutation rate and patients' clinical
      pathology characteristic. 

PMID- 26309717
TI  - Association of rs731236 polymorphism in the vitamin D receptor gene with
      degenerative disc disease: evidence from a meta-analysis.
AB  - The purpose of this study was to investigate the association between the rs731236
      polymorphism in the vitamin D receptor gene and degenerative disc disease,
      especially in Chinese. We elaborately searched the relevant studies through China
      National Knowledge Infrastructure (CNKI), PubMed and EMBASE databases. Odds
      ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the
      strength of the association. A total of 10 studies involving 1,220 cases and
      1,225 controls were included in the present study. Overall, no evidence of
      significant risk between rs731236 polymorphism and degenerative disc disease was
      found in any genetic models. In addition, stratified analyses by ethnicity
      revealed similar results. However, stratified analyses by sample size in Chinese
      population show that sample size may be the primary source of heterogeneity. This
      meta-analysis suggested that the rs731236 polymorphism may not be associated with
      degenerative disc disease. However, for Asians, there existed some diversities,
      especially in Chinese population. Therefore, a large number of well-designed
      studies are still required to assess this polymorphism and degenerative disc
      disease. 

PMID- 26309718
TI  - Association of Vitamin D receptor gene TaqI polymorphisms with tuberculosis
      susceptibility: a meta-analysis.
AB  - Vitamin D receptor (VDR) is a receptor of vitamin D3, which plays a pivotal role
      in regulating cell proliferation and differentiation, lymphocyte activation and
      cytokine production, and is associated with TB susceptibility. Growing studies
      explored the association of TaqI polymorphism of VDR with tuberculosis (TB)
      susceptibility. However, the results were inconsistent and conflicting. To assess
      the relationship between the VDR TaqI gene polymorphism and the risk of TB, a
      meta-analysis was performed. Databases including PubMed and EMbase were
      systematically searched for genetic association studies of TaqI polymorphism of
      VDR and tuberculosis until February 15, 2015. Data were extracted by two
      independent authors and pooled odds ratio (OR) with 95% confidence interval (CI)
      was calculated to assess the strength of the association between VDR TaqI gene
      polymorphism and TB risk, meta-regression and subgroup analyses were performed to
      identify the source of heterogeneity. Thirty-eight studies with a total of 6881
      cases and 7511 controls were reviewed in the present meta-analysis. A
      statistically significant correlations were observed between VDR TaqI gene
      polymorphism and TB risk in South and West Asians (t vs. T: OR=1.27, 95% CI=1.07
      1.51, P=0.007; tt vs. TT: OR=1.59, 95% CI=1.11-2.26, P=0.011; tt vs. Tt + TT:
      OR=1.43, 95% CI=1.17-1.73, P=0.000; tt + Tt vs. TT: OR=1.32, 95% CI=1.05-1.67,
      P=0.019). Heterogeneity between studies was not pronounced, and meta-regression
      found no source contributed to heterogeneity. However, after stratified analysis
      with respect to genotyping methods and sample size, significant association was
      found in "small" studies (<500 participants) and studies with "PCR-RFLP" methods.
      Synthesis of the available studies suggests that t allele of the VDR TaqI
      polymorphism is significantly associated with an increased TB risk in South and
      West Asians. 

PMID- 26309719
TI  - Evaluation of levator ani with no defect on elastography in women with POP.
AB  - OBJECTIVE: It is difficult to evaluate the function of levator ani with no defect
      encountered in routine practice. Elastography is a new adjunct to real-time
      ultrasound imaging that overlays traditional B-mode imaging with a color graphic
      representation of tissue elasticity. The aim of this study is to specifically
      evaluate the function of levator ani with no defect by ES (elastography).
      METHODS: This was a prospective, observational study. All patients were examined
      by MRI and the cases with levator ani defect were excluded. The included cases
      underwent conventional translabial ultrasound, and then ultrasound ES. A little
      levator ani were biopsied for immunohistochemistry check in the patients who
      underwent surgery. RESULTS: Of the 52 cases with no levator ani defects, 22 had
      an elastography score of 1, 20 had a score of 2, 8 had a score of 3 and 2 had a
      score of 4 in levator ani. Cases of ES1 and ES2 were more than ES3 and ES4 (P =
      0.004). The immunohistochemistry check indicated that 12 patients who underwent
      surgery showed weak expression and the other 4 patients showed moderate
      expression of collagen type I in levator ani, compared with 2 controls showing
      strong expressions. CONCLUSIONS: Elastography can assess the change of elasticity
      function of levator ani though the structure has no defect which was detected by
      MRI and conventional ultrasound. And probably the change of function of levator
      ani was earlier than structure abnormity in POP.

PMID- 26309720
TI  - Local anaesthetic wound infiltration used for caesarean section pain relief: a
      meta-analysis.
AB  - PURPOSE: Local anaesthetic wound infiltration techniques were reported to reduce
      opiate requirements and pain scores in women undergoing caesarean section (CS).
      However, the results were conflicting. The primary aim of this meta-analysis was
      to assess whether local analgesia could reduce pain intensity when injected via
      wound catheters. METHODS: A search of randomized clinical trials (RCTs)
      evaluating local analgesia in caesarean surgery in PubMed, EMBASE and the
      Cochrane database was performed. Cumulative morphine consumption and pain scores
      at rest at different time point after surgery were extracted and synthesized
      using random or fixed model for meta-analysis. Subgroup analysis was performed
      according to incision type and administration regimen. RESULTS: Nine RCTs with a
      total of 512 patients were included. Cumulative morphine consumption was lower in
      LA group compared with placebo group in the first 12 h (SMD = -0.736, 95% CI (
      1.105, -0.368)), 24 h (SMD = -0.378, 95% CI (-0.624, -0.132)) and 48 h after
      surgery (SMD = -0.913, 95% CI (-1.683 to -0.143)). Lower morphine consumption was
      observed in the first 6 h after surgery but the reduction failed to meet the
      common level of significance. Pain scores was significantly reducedat 12 h but
      not 6 h after surgery in the LA group compared with placebo group. At 24 h and 48
      h after surgery, the pain sore was lower but the difference did not meet the
      common level of significance. Lower rate of post-operative nausea was observed in
      the LA group. CONCLUSIONS: Local anaesthetic wound infiltration can reduce
      morphine requirements and the rate of patients suffer nausea but not pain scores
      after caesarean section. Further procedure-specific RCTs were encouraged to
      confirm the efficacy of local anaesthetic wound infiltration techniques.

PMID- 26309722
TI  - The actinin family proteins: biological function and clinical implications.

PMID- 26309721
TI  - Molecular characterization of HIV-1 genome in fission yeast Schizosaccharomyces
      pombe.
AB  - BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) genome (~9 kb RNA) is
      flanked by two long terminal repeats (LTR) promoter regions with nine open
      reading frames, which encode Gag, Pol and Env polyproteins, four accessory
      proteins (Vpu, Vif, Vpr, Nef) and two regulatory proteins (Rev, Tat). In this
      study, we carried out a genome-wide and functional analysis of the HIV-1 genome
      in fission yeast (Schizosaccharomyces pombe). RESULTS: Each one of the HIV-1
      genes was cloned and expressed individually in fission yeast. Subcellular
      localization of each viral protein was first examined. The effect of protein
      expression on cellular proliferation and colony formations, an indication of
      cytotoxicity, were observed. Overall, there is a general correlation of
      subcellular localization of each viral protein between fission yeast and
      mammalian cells. Three viral proteins, viral protein R (Vpr), protease (PR) and
      regulator of expression of viral protein (Rev), were found to inhibit cellular
      proliferation. Rev was chosen for further analysis in fission yeast and mammalian
      cells. Consistent with the observation in fission yeast, expression of HIV-1 rev
      gene also caused growth retardation in mammalian cells. However, the observed
      growth delay was neither due to the cytotoxic effect nor due to alterations in
      cell cycling. Mechanistic testing of the Rev effect suggests it triggers
      transient induction of cellular oxidative stress. CONCLUSIONS: Some of the
      behavioral and functional similarities of Rev between fission yeast and mammalian
      cells suggest fission yeast might be a useful model system for further studies of
      molecular functions of Rev and other HIV-1 viral proteins.

PMID- 26309723
TI  - Immunological events in chronic spontaneous urticaria.
AB  - Chronic spontaneous urticaria (CSU) is a highly debilitating skin disease
      associated with systemic features. We have made significant progress in several
      aspects relating to this condition. However, the exact physiopathology remains
      unknown. There is mounting evidence for an autoimmune basis, demonstrated by the
      CSU serum ability to activate healthy donors skin mast cells and blood basophils.
      However, it is only seen among 35-40% of patients. Mast cells and basophils play
      an important role in this skin condition. Both cells in CSU patients have unique
      features that differentiate them from basophils and mast cells from healthy
      donors. In the case of basophils, basopenia is typically found in CSU patients.
      Basophils from CSU patients also tend to be hyporesponsive to stimuli that act
      through the IgE receptor, responsive to other stimuli as MCP-1 or C5a, and
      hyperesponsive when incubated with sera. Eosinophils are also present in CSU skin
      biopsies, yet their exact role has not yet been defined. Likewise, endothelial
      cells also play a function, as indirectly demonstrated by an increase of
      vasoactive peptides in skin and plasma of CSU patients' samples. All these facts
      orchestrate a systemic inflammation response producing a significant increase of
      several inflammatory markers. Unfortunately, we lack a unitary model that could
      explain the exact role of each of these players. In this review, we will describe
      the history and discover the pathway to the present knowledge on the
      immunological facts of this disease. 

PMID- 26309724
TI  - Comparison of rapid laboratory tests for failure of passive transfer in the
      bovine.
AB  - BACKGROUND: Failure of passive transfer of maternal immunity via colostrum can
      occur in the bovine, and a number of blood tests have been developed to test
      calves for this failure. It is not clear which test is most suitable for this
      purpose. The objective was to examine the most commonly used tests for failure of
      passive transfer and to decide which is most suitable for routine laboratory use.
      126 serum samples were taken from calves of dairy cows after birth but prior to
      colostrum feeding, and at 48 h of age. Five different tests were compared against
      radial immunodiffusion which is considered the appropriate reference method.
      These tests were serum gamma-glutamyltransferase levels, serum protein levels,
      serum globulin levels, an enzyme linked immunosorbent assay and the zinc sulphate
      turbidity test. RESULTS: The tests examined displayed high sensitivity but widely
      varying specificity. Examination of the use of different cut-off points allowed
      some improvement in specificity at the expense of sensitivity, but the tests
      which had performed best at the original cut-off points still displayed the best
      performance. Gamma-glutamyltransferase levels as a measure of colostrum
      absorption returned, in this study, the best balance between sensitivity and
      specificity. The ELISA used in this study and serum globulin levels displayed
      performance similar to the gamma-glutamyltransferase levels. Serum total protein
      was less successful than others examined at providing both sensitivity and
      specificity but may, when performed via refractometer, be useful for on-farm
      testing. As currently performed the poor sensitivity for which the zinc sulphate
      turbidity test is most often criticized is evident. Modification of the cut-off
      point to increase specificity is less successful at balancing these parameters
      than the ELISA, gamma-glutamyltransferase levels, and globulin levels.
      CONCLUSIONS: Gamma-glutamyltransferase levels, ELISA testing and circulating
      globulin levels performed best in detecting failure of passive transfer in serum
      samples, although all three had some practical considerations.

PMID- 26309726
TI  - Ketamine infusion for patients receiving extracorporeal membrane oxygenation
      support: a case series.
AB  - The use of ketamine infusion for sedation/analgesia in patients receiving
      extracorporeal membrane oxygenation (ECMO) therapy has not been described. The
      aims of this retrospective cohort study were to explore whether ketamine infusion
      for patients requiring ECMO therapy was associated with altered RASS scores,
      decreased concurrent sedative or opioid use, or with changes in vasopressor
      requirements.  All patients on ECMO who received ketamine infusions in addition
      to sedative and/or opioid infusions between December 2013 and October 2014 at
      Barnes-Jewish Hospital in St. Louis were retrospectively identified. Patient
      characteristics and process of care data were collected. A total of 26 ECMO
      patients receiving ketamine infusion were identified. The median (inter quartile
      range [range]) age was 40 years (30-52 [25-66]) with 62% male. The median
      starting infusion rate of ketamine was 50 mg/hr (30-50 [6-150]) and it was
      continued for a median duration of 9 days (4-14 [0.2-21]). Prior to ketamine,
      14/26 patients were receiving vasopressor infusions to maintain hemodynamic
      stability. Ketamine initiation was associated with a decrease in vasopressor
      requirement in 11/26  patients within two hours, and 0/26 required an increase
      (p<0.001). All patients were receiving sedative and/or opioid infusions at the
      time of ketamine initiation; 9/26 had a decrease in these infusions within two
      hours of ketamine initiation, and 1/26 had an increase (p=0.02; odds ratio for
      decrease to increase = 9; 95% CI, 1.14 to 71.04). The median (IQR[range]) RASS
      score 24 hours before ketamine initiation was -4 (-3 to -5, [0 to -5]) and after
      ketamine was -4 (-3 to -4 [-1 to -5]) ( P = 0.614). Ketamine infusion can be used
      as an adjunctive sedative agent in patients receiving ECMO and may decrease
      concurrent sedative and/or opioid infusions without altering RASS scores. The
      hemodynamic effects of ketamine may provide the benefit of decreasing vasopressor
      requirements. 

PMID- 26309727
TI  - Epidemiology and patterns of musculoskeletal motorcycle injuries in the USA.
AB  - INTRODUCTION: Motorcycles have become an increasingly popular mode of
      transportation despite their association with a greater risk for injury compared
      with automobiles. Whereas the recent incidence of annual passenger vehicle
      fatalities in the United States of America (USA) has progressively declined,
      motorcycle fatalities have steadily increased in the past 11 years. Although
      motorcycle injuries (MIs) have been studied, to the author's knowledge there are
      no published reports on MIs in the USA during this 11-year period. Methods :
      Study data were derived from a prospectively collected Level I trauma center
      database. Data sampling included motorcycle crash injury evaluations for the 10
      year period ending on 31 August 2008. This retrospective analysis included
      patient demographic and medical data, helmet use, Glasgow coma scale (GCS) score,
      injury severity score (ISS), length of hospital stay (LOS), specific injury
      diagnosis, and death. Data statistics were analyzed using the Spearman
      correlation coefficient, Kruskal-Wallis tests, and logistic regression. RESULTS:
      The study identified 1252 motorcycle crash injuries. Helmets were worn by 40.7%
      of patients for which helmet data were available. The rates of the most common
      orthopedic injuries were tibia/fibula (19.01%), spine (16.21%), and forearm
      (10.14%) fractures. The most common non-orthopedic motorcycle crash injuries were
      concussions (21.09%), skull fractures (8.23%), face fractures (13.66%), and hemo-
      and pneumothorax (8.79%). There was a significant correlation between greater age
      and higher ISS (r=0.21, P<0.0001) and longer LOS (r=0.22, P<0.0001). Older
      patients were also less likely to wear a helmet (OR=0.99, 95% CI: 0.98, 0.997),
      associated with a significantly higher risk for death (after adjustment for
      helmet use OR=1.03, 95% CI: 1.00, 1.05). All patients without helmets had a
      significantly lower GCS score (P=0.0001) and a higher mortality rate (after
      adjustment for patient demographic data OR=2.28, 95% CI: 1.13, 4.58).  Conclusion
      : Compared with historical reports, the prevalence of skull, face, spine, and
      pelvis fractures have increased in American motorcycle crashes. Compared to
      recent European studies, the incidence of USA skull and face fractures is much
      higher, while the incidence of USA spine and pelvis fractures is more comparable;
      however, this is not associated with increased in-hospital mortality.

PMID- 26309728
TI  - Non-invasive imaging to monitor lupus nephritis and neuropsychiatric systemic
      lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect
      multiple different organs, including the kidneys and central nervous system
      (CNS). Conventional radiological examinations in SLE patients include volumetric/
      anatomical computed tomography (CT), magnetic resonance imaging (MRI) and
      ultrasound (US). The utility of these modalities is limited, however, due to the
      complexity of the disease. Furthermore, CT and MRI contrast agents are
      contraindicated in patients with renal impairment. Various radiologic methods are
      currently being developed to improve disease characterization in patients with
      SLE beyond simple anatomical endpoints. Physiological non-contrast MRI protocols
      have been developed to assess tissue oxygenation, glomerular filtration, renal
      perfusion, interstitial diffusion, and inflammation-driven fibrosis in lupus
      nephritis (LN) patients. For neurological symptoms, vessel size imaging (VSI, an
      MRI approach utilizing T2-relaxing iron oxide nanoparticles) has shown promise as
      a diagnostic tool. Molecular imaging probes (mostly for MRI and nuclear medicine
      imaging) have also been developed for diagnosing SLE with high sensitivity, and
      for monitoring disease activity. This paper reviews the challenges in evaluating
      disease activity in patients with LN and neuropsychiatric systemic lupus
      erythematosus (NPSLE). We describe novel MRI and positron-emission tomography
      (PET) molecular imaging protocols using targeted iron oxide nanoparticles and
      radioactive ligands, respectively, for detection of SLE-associated inflammation. 

PMID- 26309725
TI  - Development of an image-based screening system for inhibitors of the plastidial
      MEP pathway and of protein geranylgeranylation.
AB  - In a preceding study we have recently established an in vivo visualization system
      for the geranylgeranylation of proteins in a stably transformed tobacco BY-2 cell
      line, which involves expressing a dexamethasone-inducible GFP fused to the
      prenylable, carboxy-terminal basic domain of the rice calmodulin CaM61, which
      naturally bears a CaaL geranylgeranylation motif (GFP-BD-CVIL). By using pathway
      specific inhibitors it was there demonstrated that inhibition of the
      methylerythritol phosphate (MEP) pathway with oxoclomazone and fosmidomycin, as
      well as inhibition of protein geranylgeranyl transferase type 1 (PGGT-1), shifted
      the localization of the GFP-BD-CVIL protein from the membrane to the nucleus. In
      contrast, the inhibition of the mevalonate (MVA) pathway with mevinolin did not
      affect this localization. Furthermore, in this initial study complementation
      assays with pathway-specific intermediates confirmed that the precursors for the
      cytosolic isoprenylation of this fusion protein are predominantly provided by the
      MEP pathway. In order to optimize this visualization system from a more
      qualitative assay to a statistically trustable medium or a high-throughput
      screening system, we established now new conditions that permit culture and
      analysis in 96-well microtiter plates, followed by fluorescence microscopy. For
      further refinement, the existing GFP-BD-CVIL cell line was transformed with an
      estradiol-inducible vector driving the expression of a RFP protein, C-terminally
      fused to a nuclear localization signal (NLS-RFP). We are thus able to quantify
      the total number of viable cells versus the number of inhibited cells after
      various treatments. This approach also includes a semi-automatic counting system,
      based on the freely available image processing software. As a result, the time of
      image analysis as well as the risk of user-generated bias is reduced to a
      minimum. Moreover, there is no cross-induction of gene expression by
      dexamethasone and estradiol, which is an important prerequisite for this test
      system. 

PMID- 26309729
TI  - Case Report: Perioperative management of a pregnant poly trauma patient for spine
      fixation surgery.
AB  - Trauma is estimated to complicate approximately one in twelve pregnancies, and is
      currently a leading non-obstetric cause of maternal death. Pregnant trauma
      patients requiring non-obstetric surgery pose a number of challenges for
      anesthesiologists. Here we present the successful perioperative management of a
      pregnant trauma patient with multiple injuries including occult pneumothorax who
      underwent T9 to L1 fusion in prone position, and address the pertinent
      perioperative anesthetic considerations and management. 

PMID- 26309730
TI  - Re-analysis of metagenomic sequences from acute flaccid myelitis patients reveals
      alternatives to enterovirus D68 infection.
AB  - Metagenomic sequence data can be used to detect the presence of infectious
      viruses and bacteria, but normal microbial flora make this process challenging.
      We re-analyzed metagenomic RNA sequence data collected during a recent outbreak
      of acute flaccid myelitis (AFM), caused in some cases by infection with
      enterovirus D68. We found that among the patients whose symptoms were previously
      attributed to enterovirus D68, one patient had clear evidence of infection with
      Haemophilus influenzae, and a second patient had a severe Staphylococcus aureus
      infection caused by a methicillin-resistant strain. Neither of these bacteria
      were identified in the original study. These observations may have relevance in
      cases that present with flaccid paralysis because bacterial infections, co
      infections or post-infection immune responses may trigger pathogenic processes
      that may present as poliomyelitis-like syndromes and may mimic AFM.  A separate
      finding was that large numbers of human sequences were present in each of the
      publicly released samples, although the original study reported that human
      sequences had been removed before deposition. 

PMID- 26309731
TI  - Journal ratings as predictors of articles quality in Arts, Humanities and Social
      Sciences: an analysis based on the Italian Research Evaluation Exercise.
AB  - The aim of this paper is to understand whether the probability of receiving
      positive peer reviews is influenced by having published in an independently
      assessed, high-ranking journal: we eventually interpret a positive relationship
      among peer evaluation and journal ranking as evidence that journal ratings are
      good predictors of article quality. The analysis is based on a large dataset of
      over 11,500 research articles published in Italy in the period 2004-2010 in the
      areas of architecture, arts and humanities, history and philosophy, law,
      sociology and political sciences. These articles received a score by a large
      number of externally appointed referees in the context of the Italian research
      assessment exercise (VQR); similarly, journal scores were assigned in a panel
      based independent assessment, which involved all academic journals in which
      Italian scholars have published, carried out under a different procedure. The
      score of an article is compared with that of the journal it is published in: more
      specifically, we first estimate an ordered probit model, assessing the
      probability for a paper of receiving a higher score, the higher the score of the
      journal; in a second step, we concentrate on the top papers, evaluating the
      probability of a paper receiving an excellent score having been published in a
      top-rated journal. In doing so, we control for a number of characteristics of the
      paper and its author, including the language of publication, the scientific field
      and its size, the age of the author and the academic status. We add to the
      literature on journal classification by providing for the first time a large
      scale test of the robustness of expert-based classification. 

PMID- 26309732
TI  - Cerebrospinal Fluid Biomarkers of Japanese Encephalitis.
AB  - Japanese encephalitis (JE) is the leading cause of viral encephalitis in Asia.
      Acute encephalitis syndrome (AES) is a group of central nervous system (CNS)
      disorders caused by a wide range of viruses, bacteria, fungi, chemicals and
      toxins. It is important to distinguish between various forms of infectious
      encephalitis with similar clinical manifestations in order to ensure specific and
      accurate diagnosis and development of subsequent therapeutic strategies.
      Cerebrospinal fluid (CSF) is in direct contact with the CNS and hence it is
      considered to be an excellent source for identifying biomarkers for various
      neurological disorders. With the recent advancement in proteomic methodologies,
      the field of biomarker research has received a remarkable boost.  The present
      study identifies potential biomarkers for JE using a proteomics based approach.
      The CSF proteomes from ten patients each with JE and Non-JE acute encephalitis
      were analyzed by 2D gel electrophoresis followed by mass spectrometry. Vitamin D
      binding protein (DBP), fibrinogen gamma chain, fibrinogen beta chain, complement
      C4-B, complement C3 and cytoplasmic actin were found to be significantly elevated
      in case of JE indicating severe disruption of the blood brain barrier and DBP can
      be suggested to be an important diagnostic marker. 

PMID- 26309734
TI  - Bacteriophages as antimicrobial agents against major pathogens in swine: a
      review.
AB  - In recent years, the development of antibiotic resistant bacteria has become a
      global concern which has prompted research into the development of alternative
      disease control strategies for the swine industry. Bacteriophages (viruses that
      infect bacteria) offer the prospect of a sustainable alternative approach against
      bacterial pathogens with the flexibility of being applied therapeutically or for
      biological control purposes. This paper reviews the use of phages as an
      antimicrobial strategy for controlling critical pathogens including Salmonella
      and Escherichia coli with an emphasis on the application of phages for improving
      performance and nutrient digestibility in swine operations as well as in
      controlling zoonotic human diseases by reducing the bacterial load spread from
      pork products to humans through the meat. 

PMID- 26309735
TI  - Chicken egg yolk antibodies (IgY) as non-antibiotic production enhancers for use
      in swine production: a review.
AB  - In recent years, the use of in-feed antibiotics for growth and disease prevention
      in livestock production has been under severe scrutiny. The use and misuse of in
      feed antibiotics has led to problems with drug residues in animal products and
      increased bacterial resistance. Chicken egg yolk antibodies (IgY) have attracted
      considerable attention as an alternative to antibiotics to maintain swine health
      and performance. Oral administration of IgY possesses many advantages over
      mammalian IgG such as cost-effectiveness, convenience and high yield. This review
      presents an overview of the potential to use IgY immunotherapy for the prevention
      and treatment of swine diarrhea diseases and speculates on the future of IgY
      technology. Included are a review of the potential applications of IgY in the
      control of enteric infections of either bacterial or viral origin such as
      enterotoxigenic Escherichia coli, Salmonella spp., rotavirus, porcine
      transmissible gastroenteritis virus, and porcine epidemic diarrhea virus. Some
      potential obstacles to the adoption of IgY technology are also discussed. 

PMID- 26309736
TI  - Disparities in healthy food zoning, farmers' market availability, and fruit and
      vegetable consumption among North Carolina residents.
AB  - BACKGROUND: Context and purpose of the study. To examine (1) associations between
      county-level zoning to support farmers' market placement and county-level
      farmers' market availability, rural/urban designation, percent African American
      residents, and percent of residents living below poverty and (2) individual-level
      associations between zoning to support farmers' markets; fruit and vegetable
      consumption and body mass index (BMI) among a random sample of residents of six
      North Carolina (NC) counties. METHODS: Zoning ordinances were scored to indicate
      supportiveness for healthy food outlets. Number of farmers' markets (per capita)
      was obtained from the NC-Community Transformation Grant Project Fruit and
      Vegetable Outlet Inventory (2013). County-level census data on rural/urban
      status, percent African American, and percent poverty were obtained. For data on
      farmers' market shopping, fruit and vegetable consumption, and BMI, trained
      interviewers conducted a random digit dial telephone survey of residents of six
      NC counties (3 urban and 3 rural). Pearson correlation coefficients and
      multilevel linear regression models were used to examine county-level and
      individual-level associations between zoning supportiveness, farmers' market
      availability, and fruit and vegetable consumption and BMI. RESULTS: At the county
      level, healthier food zoning was greater in more urban areas and areas with less
      poverty. At the individual-level, self-reported fruit and vegetable consumption
      was associated with healthier food zoning. CONCLUSIONS: Disparities in zoning to
      promote healthy eating should be further examined, and future studies should
      assess whether amending zoning ordinances will lead to greater availability of
      healthy foods and changes in dietary behavior and health outcomes.

PMID- 26309737
TI  - The enemy within: the association between self-image and eating disorder symptoms
      in healthy, non help-seeking and clinical young women.
AB  - BACKGROUND: Previous research has shown self-image according to the interpersonal
      Structural Analysis of Social Behavior model, to relate to and predict eating
      disorder symptoms and outcomes. METHODS: We examined associations between self
      reported self-image and ED symptoms in three groups of 16-25 year old females:
      healthy (N = 388), non help-seeking (N = 227) and clinical (N = 6384). Analyses
      were divided into age groups of 16-18 and 19-25 years, and the patient sample was
      divided into diagnostic groups. RESULTS: Stepwise regressions with self-image
      aspects as independent variables and eating disorder symptoms as dependent showed
      that low self-love/acceptance and high self-blame were associated with more
      eating disorder symptoms in all groups, except older patients with bulimia
      nervosa where self-hate also contributed. Associations were generally weaker in
      the healthy groups and the older samples. CONCLUSIONS: We put forward that older
      age, low desirability of symptoms, poorly working symptoms, and being
      acknowledged as ill, may weaken the association, with implications for treatment
      and prevention.

PMID- 26309738
TI  - Medical rescue of naval combat: challenges and future.
AB  - There has been no large-scale naval combat in the last 30 years. With the rapid
      development of battleships, weapons manufacturing and electronic technology,
      naval combat will present some new characteristics. Additionally, naval combat is
      facing unprecedented challenges. In this paper, we discuss the topic of medical
      rescue at sea: what challenges we face and what we could do. The contents
      discussed in this paper contain battlefield self-aid buddy care, clinical skills,
      organized health services, medical training and future medical research programs.
      We also discuss the characteristics of modern naval combat, medical rescue
      challenges, medical treatment highlights and future developments of medical
      rescue at sea. 

PMID- 26309733
TI  - Visualizing genome and systems biology: technologies, tools, implementation
      techniques and trends, past, present and future.
AB  - "Alpha picture is worth a thousand words." This widely used adage sums up in a
      few words the notion that a successful visual representation of a concept should
      enable easy and rapid absorption of large amounts of information. Although, in
      general, the notion of capturing complex ideas using images is very appealing,
      would 1000 words be enough to describe the unknown in a research field such as
      the life sciences? Life sciences is one of the biggest generators of enormous
      datasets, mainly as a result of recent and rapid technological advances; their
      complexity can make these datasets incomprehensible without effective
      visualization methods. Here we discuss the past, present and future of genomic
      and systems biology visualization. We briefly comment on many visualization and
      analysis tools and the purposes that they serve. We focus on the latest libraries
      and programming languages that enable more effective, efficient and faster
      approaches for visualizing biological concepts, and also comment on the future
      human-computer interaction trends that would enable for enhancing visualization
      further. 

PMID- 26309739
TI  - Discrimination of liver malignancies with 1064 nm dispersive Raman spectroscopy.
AB  - Raman spectroscopy has been widely demonstrated for tissue characterization and
      disease discrimination, however current implementations with either 785 or 830 nm
      near-infrared (NIR) excitation have been ineffectual in tissues with intense
      autofluorescence such as the liver. Here we report the use of a dispersive 1064
      nm Raman system using a low-noise Indium-Gallium-Arsenide (InGaAs) array to
      discriminate highly autofluorescent bulk tissue ex vivo specimens from healthy
      liver, adenocarcinoma, and hepatocellular carcinoma (N = 5 per group). The
      resulting spectra have been combined with a multivariate discrimination
      algorithm, sparse multinomial logistic regression (SMLR), to predict class
      membership of healthy and diseased tissues, and spectral bands selected for
      robust classification have been extracted. A quantitative metric called feature
      importance is defined based on classification outputs and is used to guide the
      association of spectral features with biological indicators of healthy and
      diseased liver tissue. Spectral bands with high feature importance for healthy
      and liver tumor specimens include retinol, heme, biliverdin, or quinones (1595
      cm(-1)); lactic acid (838 cm(-1)); collagen (873 cm(-1)); and nucleic acids (1485
      cm(-1)). Classification performance in both binary (normal versus tumor, 100%
      sensitivity and 89% specificity) and three-group cases (classification accuracy:
      normal 89%, adenocarcinoma 74%, hepatocellular carcinoma 64%) indicates the
      potential for accurately separating healthy and cancerous tissues and suggests
      implications for utilizing Raman techniques during surgical guidance in liver
      resection. 

PMID- 26309740
TI  - OCT angiography by absolute intensity difference applied to normal and diseased
      human retinas.
AB  - We compare four optical coherence tomography techniques for noninvasive
      visualization of microcapillary network in the human retina and murine cortex. We
      perform phantom studies to investigate contrast-to-noise ratio for angiographic
      images obtained with each of the algorithm. We show that the computationally
      simplest absolute intensity difference angiographic OCT algorithm that bases only
      on two cross-sectional intensity images may be successfully used in clinical
      study of healthy eyes and eyes with diabetic maculopathy and branch retinal vein
      occlusion. 

PMID- 26309741
TI  - Evaluation of hybrid algorithm for analysis of scattered light using ex vivo
      nuclear morphology measurements of cervical epithelium.
AB  - We evaluate a new hybrid algorithm for determining nuclear morphology using angle
      resolved low coherence interferometry (a/LCI) measurements in ex vivo cervical
      tissue. The algorithm combines Mie theory based and continuous wavelet transform
      inverse light scattering analysis. The hybrid algorithm was validated and
      compared to traditional Mie theory based analysis using an ex vivo tissue data
      set. The hybrid algorithm achieved 100% agreement with pathology in
      distinguishing dysplastic and non-dysplastic biopsy sites in the pilot study.
      Significantly, the new algorithm performed over four times faster than
      traditional Mie theory based analysis. 

PMID- 26309742
TI  - Spontaneous and coherent anti-Stokes Raman spectroscopy of human gastrocnemius
      muscle biopsies in CH-stretching region for discrimination of peripheral artery
      disease.
AB  - Peripheral Artery Disease (PAD) is a common manifestation of atherosclerosis,
      characterized by lower leg ischemia and myopathy in association with leg
      dysfunction. In the present study, Spontaneous and coherent anti-Stokes Raman
      scattering (CARS) spectroscopic techniques in CH-stretching spectral region were
      evaluated for discriminating healthy and diseased tissues of human gastrocnemius
      biopsies of control and PAD patients. Since Raman signatures of the tissues in
      the fingerprint region are highly complex and CH containing moieties are dense,
      CH-stretching limited spectral range was used to classify the diseased tissues. A
      total of 181 Raman spectra from 9 patients and 122 CARS spectra from 12 patients
      were acquired. Due to the high dimensionality of the data in Raman and CARS
      measurements, principal component analysis (PCA) was first performed to reduce
      the dimensionality of the data (6 and 9 principal scores for Raman and CARS,
      respectively) in the CH-stretching region, followed by a discriminant function
      analysis (DFA) to classify the samples into different categories based on disease
      severity. The CH2 and CH3 vibrational signatures were observed in the Raman and
      CARS spectroscopy. Raman and CARS data in conjunction with PCA-DFA analysis were
      capable of differentiating healthy and PAD gastrocnemius with an accuracy of
      85.6% and 78.7%, respectively. 

PMID- 26309743
TI  - Macro-optical trapping for sample confinement in light sheet microscopy.
AB  - Light sheet microscopy is a powerful approach to construct three-dimensional
      images of large specimens with minimal photo-damage and photo-bleaching. To date,
      the specimens are usually mounted in agents such as agarose, potentially
      restricting the development of live samples, and also highly mobile specimens
      need to be anaesthetized before imaging. To overcome these problems, here we
      demonstrate an integrated light sheet microscope which solely uses optical forces
      to trap and hold the sample using a counter-propagating laser beam geometry.
      Specifically, tobacco plant cells and living Spirobranchus lamarcki larvae were
      successfully trapped and sectional images acquired. This novel approach has the
      potential to significantly expand the range of applications for light sheet
      imaging. 

PMID- 26309744
TI  - Multiregional functional near-infrared spectroscopy reveals globally symmetrical
      and frequency-specific patterns of superficial interference.
AB  - Linear regression with short source-detector separation channels (S-channels) as
      references is an efficient way to overcome significant physiological interference
      from the superficial layer for functional near-infrared spectroscopy (fNIRS).
      However, the co-located configuration of S-channels and long source-detector
      separation channels (L-channels) is difficult to achieve in practice. In this
      study, we recorded superficial interference with S-channels in multiple scalp
      regions. We found that superficial interference has overall frequency-specific
      and globally symmetrical patterns. The performance of linear regression is also
      dependent on these patterns, indicating the possibility of simplifying the S
      channel configurations for multiregional fNIRS imaging. 

PMID- 26309745
TI  - Translational label-free nonlinear imaging biomarkers to classify the human
      corneal microstructure.
AB  - Diseases that affect the cornea can lead to severe vision loss and have
      tremendous social impact. These diseases are associated to deviations from normal
      structural order and orientation of collagen fibril bundles. Unfortunately,
      resolving non-invasively the corneal collagen structure is not possible to date.
      In this work, polarization sensitive second harmonic generation (pSHG) microscopy
      is used to obtain information with molecular specificity on microstructure of
      human corneas. This information is used to develop a set of label-free imaging
      biomarkers that were generated by means of a novel methodology based on
      mathematical tensorial calculus. The method is proven to be highly sensitive and
      robust. The use of these biomarkers permits accurate characterization of the
      anisotropic, depth-dependent, structural organization of corneal collagen fibril
      bundles without any a priori information. The method can be valuable to improve
      understanding of microstructural pathophysiological changes of the human cornea
      close to in vivo conditions. 

PMID- 26309746
TI  - Near-infrared spectroscopic photoacoustic microscopy using a multi-color fiber
      laser source.
AB  - We demonstrate a simple multi-wavelength optical source suitable for
      spectroscopic optical resolution photoacoustic microscopy (OR-PAM) of lipid-rich
      tissue. 1064 nm laser pulses are converted to multiple wavelengths beyond 1300 nm
      via nonlinear optical propagation in a birefringent optical fiber. OR-PAM
      experiments with lipid phantoms clearly show the expected absorption peak near
      1210 nm. We believe this simple multi-color technique is a promising cost
      effective approach to spectroscopic OR-PAM of lipid-rich tissue. 

PMID- 26309747
TI  - Rapid and noninvasive technique to assess the metabolomics profile of bovine
      embryos produced in vitro by Raman spectroscopy.
AB  - Morphological assessments are used to select embryos with the highest
      implantation potential, however it is still very limited. The development of new
      technologies, such as Raman spectroscopy have improved quantitative and
      qualitative analysis, and consequently led to a better characterization of
      embryos and improvements on the prediction of their potential. Therefore, we
      propose a method based on the conventional in vitro culture system of bovine
      embryos, and the subsequent analysis of the culture media drops by Raman
      spectroscopy. Our results obtained by PCA analysis clearly showed a separation of
      the spectral profiles from culture media drops with and without embryos. 

PMID- 26309748
TI  - Measuring oxygen saturation in retinal and choroidal circulations in rats using
      visible light optical coherence tomography angiography.
AB  - Visible light optical coherence tomography (vis-OCT) has demonstrated its
      capability of measuring vascular oxygen saturation (sO2) in vivo. Enhanced by OCT
      angiography, the signal from microvasculature can be further isolated and
      directly used for sO2 extraction. In this work, we extended the theoretical
      formulation for OCT angiography-based oximetry by incorporating the contribution
      from motion contrast enhancement. We presented a new method to eliminate the
      associated confounding variables due to blood flow. First, we performed in vitro
      experiments to verify our theory, showing a stable spectral derivative within the
      selected wavelength bands for sO2 extraction. Then, we tested our method in vivo
      to measure retinal sO2 in rats inhaling different gas mixtures: normal air, 5%
      CO2, pure O2, and 10% O2. Absolute sO2 values in major arterioles and venules in
      the retinal circulation can be accurately measured. In addition, we demonstrated
      the relative changes of sO2 can be measured non-invasively from choriocapillaris
      immediately underneath the retinal pigmented epithelium (RPE) in rodents. 

PMID- 26309749
TI  - Resolution enhancement in integral microscopy by physical interpolation.
AB  - Integral-imaging technology has demonstrated its capability for computing depth
      images from the microimages recorded after a single shot. This capability has
      been shown in macroscopic imaging and also in microscopy. Despite the possibility
      of refocusing different planes from one snap-shot is crucial for the study of
      some biological processes, the main drawback in integral imaging is the
      substantial reduction of the spatial resolution. In this contribution we report a
      technique, which permits to increase the two-dimensional spatial resolution of
      the computed depth images in integral microscopy by a factor of ?2. This is made
      by a double-shot approach, carried out by means of a rotating glass plate, which
      shifts the microimages in the sensor plane. We experimentally validate the
      resolution enhancement as well as we show the benefit of applying the technique
      to biological specimens. 

PMID- 26309750
TI  - Erratum: An adaptive optics imaging system designed for clinical use: publisher's
      note.
AB  - This publisher's note amends the author list and Acknowledgments of a recent
      publication [Biomed. Opt. Express6, 2120 (2015)].[This corrects the article on p.
      2120 in vol. 6, PMID: 26114033.]. 

PMID- 26309751
TI  - High-speed multi-exposure laser speckle contrast imaging with a single-photon
      counting camera.
AB  - Laser speckle contrast imaging (LSCI) has emerged as a valuable tool for cerebral
      blood flow (CBF) imaging. We present a multi-exposure laser speckle imaging
      (MESI) method which uses a high-frame rate acquisition with a negligible inter
      frame dead time to mimic multiple exposures in a single-shot acquisition series.
      Our approach takes advantage of the noise-free readout and high-sensitivity of a
      complementary metal-oxide-semiconductor (CMOS) single-photon avalanche diode
      (SPAD) array to provide real-time speckle contrast measurement with high temporal
      resolution and accuracy. To demonstrate its feasibility, we provide comparisons
      between in vivo measurements with both the standard and the new approach
      performed on a mouse brain, in identical conditions. 

PMID- 26309752
TI  - Experimental system for measuring the full scattering profile of circular
      phantoms.
AB  - Optical methods for monitoring physiological tissue state are important and
      useful because they are non-invasive and sensitive. Experimental measurements of
      the full scattering profile of circular phantoms are presented. We report, for
      the first time, an experimental observation of a typical reflected light
      intensity behavior for a circular structure characterized by the isobaric point.
      We previously suggested a new theoretically method for measuring the full
      scattering profile, which is the angular distribution of light intensity, of
      cylindrical tissues. In this work we present that the experimental result match
      the simulation results. We show the isobaric point at 105 degrees  for a
      cylindrical phantom with a 7mm diameter, while for a 16mm diameter phantom the
      isobaric point is at 125 degrees . Furthermore, the experimental work present a
      new crossover point of the full scattering profiles of subjects with different
      diameters of the cylindrical tissues. 

PMID- 26309753
TI  - Fluorescence and reflectance spectral imaging system for a murine mammary window
      chamber model.
AB  - A spectral imaging system was developed to study the development of breast cancer
      xenografts in a murine mammary window chamber model. The instrument is configured
      to work with either a laser to excite fluorescence or a broadband light source
      for diffuse reflectance imaging. Two applications were demonstrated. First,
      spectral imaging of fluorescence signals was demonstrated with a GFP-breast
      cancer tumor and fluorescein injection. Second, based on the principles of
      broadband reflectance spectroscopy, the instrument was used to monitor dynamic
      changes of tissue absorbance to yield tissue oxygenation maps at different time
      points during tumor progression. 

PMID- 26309754
TI  - Beat-to-beat heart rate estimation fusing multimodal video and sensor data.
AB  - Coverage and accuracy of unobtrusively measured biosignals are generally
      relatively low compared to clinical modalities. This can be improved by
      exploiting redundancies in multiple channels with methods of sensor fusion. In
      this paper, we demonstrate that two modalities, skin color variation and head
      motion, can be extracted from the video stream recorded with a webcam. Using a
      Bayesian approach, these signals are fused with a ballistocardiographic signal
      obtained from the seat of a chair with a mean absolute beat-to-beat estimation
      error below 25 milliseconds and an average coverage above 90% compared to an ECG
      reference. 

PMID- 26309755
TI  - Selective detection of bacteria in urine with a long-range surface plasmon
      waveguide biosensor.
AB  - Experimentation demonstrates long-range surface plasmon polariton waveguides as a
      useful biosensor to selectively detect gram negative or gram positive bacteria in
      human urine having a low concentration of constituents. The biosensor can detect
      bacteria at concentrations of 10(5) CFU/ml, the internationally recommended
      threshold for diagnostic of urinary tract infection. Using a negative control
      urine solution of bacterial concentration 1000? higher than the targeted
      bacteria, we obtain a ratio of 5.4 for the positive to negative signals. 

PMID- 26309756
TI  - Dual-pulse nonlinear photoacoustic technique: a practical investigation.
AB  - The dual-pulse nonlinear photoacoustic technique is a recently developed
      technology based on temperature dependence of the Gruneisen parameter and
      involves consecutive excitations of biological tissue using two laser pulses with
      a short time delay. Here we review the principle of the technique and give a
      discussion about its technical aspects, including selection and combination of
      excitation laser wavelengths, determination of laser fluence, estimation of
      thermal relaxation function and probability of photoablation or cavitation.
      Comparisons between the dual-pulse technique and conventional photoacoustics as
      well as thermal photoacoustics are also presented. These investigations are
      supported by experimental results and will give a practical reference and guide
      for further developments of the technique. 

PMID- 26309757
TI  - Characterizing microstructures of cancerous tissues using multispectral
      transformed Mueller matrix polarization parameters.
AB  - In this paper, we take the transmission 3 * 3 linear polarization Mueller matrix
      images of the unstained thin slices of human cervical and thyroid cancer tissues,
      and analyze their multispectral behavior using the Mueller matrix transformation
      (MMT) parameters. The experimental results show that for both cervical and
      thyroid cancerous tissues, the characteristic features of multispectral
      transmitted MMT parameters can be used to distinguish the normal and abnormal
      areas. Moreover, Monte Carlo simulations based on the sphere-cylinder
      birefringence model (SCBM) provide additional information of the relations
      between the characteristic spectral features of the MMT parameters and the
      microstructures of the tissues. Comparisons between the experimental and
      simulated data confirm that the contrast mechanism of the transmission MMT
      imaging for cancer detection is the breaking down of birefringent normal tissues
      for cervical cancer, or the formation of birefringent surrounding structures
      accompanying the inflammatory reaction for thyroid cancer. It is also testified
      that, the characteristic spectral features of polarization imaging techniques can
      provide more detailed microstructural information of tissues for diagnosis
      applications. 

PMID- 26309758
TI  - Resolution doubling with a reduced number of image acquisitions.
AB  - Structured illumination technique enhances the lateral resolution by projecting
      non-uniform intensity patterns on a sample. In a typical implementation, three
      lateral phase shifts (0, 2pi/3, 4pi/3) are needed for each orientation of the
      sinusoidal pattern, and 3 different orientations are needed to double the
      bandwidth isotopically in the Fourier domain. To this end, 9 incoherent images
      are needed in the acquisition process. In this paper, we discuss an imaging
      strategy for the structured illumination technique and demonstrate the use of a
      modified incoherent Fourier ptychographic procedure for reducing the number of
      acquisitions. In the first implementation, we used complementary sinusoidal
      patterns for sample illumination. We show that, the number of lateral phase
      shifts can be reduced from 3 to 2 for each orientation of the sinusoidal pattern
      and the total number of image acquisitions can be reduced to 6 with 3
      orientations. In the second implementation, we further reduce the number of image
      acquisitions to 4. We also show that, the resolution-doubled image can be
      recovered even with unknown phases of the sinusoidal patterns. We validate the
      proposed imaging procedure with non-fluorescence samples. The reported approach
      may shorten the acquisition time of super-resolution imaging and reduce
      phototoxicity of biological samples. 

PMID- 26309759
TI  - Mechanical assessment of bovine pericardium using Mueller matrix imaging,
      enhanced backscattering and digital image correlation analysis.
AB  - Mechanical characterization of tissue is an important but complex task. We
      demonstrate the simultaneous use of Mueller matrix imaging (MMI), enhanced
      backscattering (EBS) and digital image correlation (DIC) in a bovine pericardium
      (BP) tensile test. The interest in BP relies on its wide use as valve replacement
      and biological patch. We show that the mean free path (MFP), obtained through EBS
      measurements, can be used as an indicator of the anisotropy of the fiber
      ensemble. Our results further show a good correlation between retardance images
      and displacement vector fields, which are intrinsically related with the fiber
      interaction within the tissue. 

PMID- 26309761
TI  - Rapid multispectral endoscopic imaging system for near real-time mapping of the
      mucosa blood supply in the lung.
AB  - We have developed a fast multispectral endoscopic imaging system that is capable
      of acquiring images in 18 optimized spectral bands spanning 400-760 nm by
      combining a customized light source with six triple-band filters and a standard
      color CCD camera. A method is developed to calibrate the spectral response of the
      CCD camera. Imaging speed of 15 spectral image cubes/second is achieved. A
      spectral analysis algorithm based on a linear matrix inversion approach is
      developed and implemented in a graphics processing unit (GPU) to map the mucosa
      blood supply in the lung in vivo. Clinical measurements on human lung patients
      are demonstrated. 

PMID- 26309760
TI  - Quantification and normalization of noise variance with sparsity regularization
      to enhance diffuse optical tomography.
AB  - Conventional reconstruction of diffuse optical tomography (DOT) is based on the
      Tikhonov regularization and the white Gaussian noise assumption. Consequently,
      the reconstructed DOT images usually have a low spatial resolution. In this work,
      we have derived a novel quantification method for noise variance based on the
      linear Rytov approximation of the photon diffusion equation. Specifically, we
      have implemented this quantification of noise variance to normalize the
      measurement signals from all source-detector channels along with sparsity
      regularization to provide high-quality DOT images. Multiple experiments from
      computer simulations and laboratory phantoms were performed to validate and
      support the newly developed algorithm. The reconstructed images demonstrate that
      quantification and normalization of noise variance with sparsity regularization
      (QNNVSR) is an effective reconstruction approach to greatly enhance the spatial
      resolution and the shape fidelity for DOT images. Since noise variance can be
      estimated by our derived expression with relatively limited resources available,
      this approach is practically useful for many DOT applications. 

PMID- 26309762
TI  - Investigation of temperature effect on cell mechanics by optofluidic microchips.
AB  - Here we present the results of a study concerning the effect of temperature on
      cell mechanical properties. Two different optofluidic microchips with external
      temperature control are used to investigate the temperature-induced changes of
      highly metastatic human melanoma cells (A375MC2) in the range of ~0 - 35  degrees
      C. By means of an integrated optical stretcher, we observe that cells' optical
      deformability is strongly enhanced by increasing cell and buffer-fluid
      temperature. This finding is supported by the results obtained from a second
      device, which probes the cells' ability to be squeezed through a constriction.
      Measured data demonstrate a marked dependence of cell mechanical properties on
      temperature, thus highlighting the importance of including a proper temperature
      control system in the experimental apparatus. 

PMID- 26309763
TI  - Simple wavefront correction framework for two-photon microscopy of in-vivo brain.
AB  - We present an easily implemented wavefront correction scheme that has been
      specifically designed for in-vivo brain imaging. The system can be implemented
      with a single liquid crystal spatial light modulator (LCSLM), which makes it
      compatible with existing patterned illumination setups, and provides measurable
      signal improvements even after a few seconds of optimization. The optimization
      scheme is signal-based and does not require exogenous guide-stars, repeated image
      acquisition or beam constraint. The unconstrained beam approach allows the use of
      Zernike functions for aberration correction and Hadamard functions for scattering
      correction. Low order corrections performed in mouse brain were found to be valid
      up to hundreds of microns away from the correction location. 

PMID- 26309764
TI  - Automated stereo vision instrument tracking for intraoperative OCT guided
      anterior segment ophthalmic surgical maneuvers.
AB  - Microscope-integrated intraoperative OCT (iOCT) enables imaging of tissue cross
      sections concurrent with ophthalmic surgical maneuvers. However, limited
      acquisition rates and complex three-dimensional visualization methods preclude
      real-time surgical guidance using iOCT. We present an automated stereo vision
      surgical instrument tracking system integrated with a prototype iOCT system. We
      demonstrate, for the first time, automatically tracked video-rate cross-sectional
      iOCT imaging of instrument-tissue interactions during ophthalmic surgical
      maneuvers. The iOCT scan-field is automatically centered on the surgical
      instrument tip, ensuring continuous visualization of instrument positions
      relative to the underlying tissue over a 2500 mm(2) field with sub-millimeter
      positional resolution and <1 degrees  angular resolution. Automated instrument
      tracking has the added advantage of providing feedback on surgical dynamics
      during precision tissue manipulations because it makes it possible to use only
      two cross-sectional iOCT images, aligned parallel and perpendicular to the
      surgical instrument, which also reduces both system complexity and data
      throughput requirements. Our current implementation is suitable for anterior
      segment surgery. Further system modifications are proposed for applications in
      posterior segment surgery. Finally, the instrument tracking system described is
      modular and system agnostic, making it compatible with different commercial and
      research OCT and surgical microscopy systems and surgical instrumentations. These
      advances address critical barriers to the development of iOCT-guided surgical
      maneuvers and may also be translatable to applications in microsurgery outside of
      ophthalmology. 

PMID- 26309765
TI  - Semi-automated discrimination of retinal pigmented epithelial cells in two-photon
      fluorescence images of mouse retinas.
AB  - Automated image segmentation is a critical step toward achieving a quantitative
      evaluation of disease states with imaging techniques. Two-photon fluorescence
      microscopy (TPM) has been employed to visualize the retinal pigmented epithelium
      (RPE) and provide images indicating the health of the retina. However,
      segmentation of RPE cells within TPM images is difficult due to small differences
      in fluorescence intensity between cell borders and cell bodies. Here we present a
      semi-automated method for segmenting RPE cells that relies upon multiple weak
      features that differentiate cell borders from the remaining image. These features
      were scored by a search optimization procedure that built up the cell border in
      segments around a nucleus of interest. With six images used as a test, our method
      correctly identified cell borders for 69% of nuclei on average. Performance was
      strongly dependent upon increasing retinosome content in the RPE. TPM image
      analysis has the potential of providing improved early quantitative assessments
      of diseases affecting the RPE. 

PMID- 26309766
TI  - Review of biomedical Cerenkov luminescence imaging applications.
AB  - Cerenkov radiation is a fascinating optical signal, which has been exploited for
      unique diagnostic biological sensing and imaging, with significantly expanded use
      just in the last half decade. Cerenkov Luminescence Imaging (CLI) has desirable
      capabilities for niche applications, using specially designed measurement systems
      that report on radiation distributions, radiotracer and nanoparticle
      concentrations, and are directly applied to procedures such as medicine
      assessment, endoscopy, surgery, quality assurance and dosimetry. When compared to
      the other imaging tools such as PET and SPECT, CLI can have the key advantage of
      lower cost, higher throughput and lower imaging time. CLI can also provide
      imaging and dosimetry information from both radioisotopes and linear accelerator
      irradiation. The relatively short range of optical photon transport in tissue
      means that direct Cerenkov luminescence imaging is restricted to small animals or
      near surface human use. Use of Cerenkov-excitation for additional molecular
      probes, is now emerging as a key tool for biosensing or radiosensitization. This
      review evaluates these new improvements in CLI for both medical value and
      biological insight. 

PMID- 26309767
TI  - Fluorescence depletion properties of insulin-gold nanoclusters.
AB  - Insulin-gold nanoclusters exhibit outstanding biocompatibility, photostability,
      and fluorescence quantum efficiency. However, they have never been used in
      superresolution microscopy, which requires nonlinear switching or saturation of
      fluorescence. Here we examine the fluorescence and stimulated emission depletion
      properties of gold nanoclusters. Their bleaching rate is very slow, demonstrating
      superior photostability. Surprisingly, however, the best depletion efficiency is
      less than 70%, whereas the depletion intensity requirement is much higher than
      the expectation from a simple two-level model. Fluorescence lifetime measurement
      revealed two distinct lifetime components, which indicate intersystem and reverse
      intersystem crossing during excitation. Based on population dynamic calculation,
      excellent agreement of the maximal depletion efficiency is found. Our work not
      only features the first examination of STED with metallic clusters, but also
      reveals the significance of molecular transition dynamics when considering a STED
      labeling. 

PMID- 26309768
TI  - MEMS-based multiphoton endomicroscope for repetitive imaging of mouse colon.
AB  - We demonstrate a handheld multiphoton endomicroscope with 3.4 mm distal diameter
      that can repetitively image mouse colon in vivo. A 2D resonant MEMS mirror was
      developed to perform beam scanning in a Lissajous pattern. The instrument has an
      effective numerical aperture of 0.63, lateral and axial resolution of 2.03 and
      9.02 MUm, respectively, working distance of 60 MUm, and image field-of-view of
      300 * 300 MUm(2). Hoechst was injected intravenously in mice to stain cell
      nuclei. We were able to collect histology-like images in vivo at 5 frames/sec,
      and distinguish between normal and pre-malignant colonic epithelium. 

PMID- 26309769
TI  - Design and fabrication of SiO2/TiO2 and MgO/TiO2 based high selective optical
      filters for diffuse reflectance and fluorescence signals extraction.
AB  - This paper presents the design, optimization and fabrication of 16 MgO/TiO2 and
      SiO2/TiO2 based high selective narrow bandpass optical filters. Their performance
      to extract diffuse reflectance and fluorescence signals from gastrointestinal
      tissue phantoms was successfully evaluated. The obtained results prove their
      feasibility to correctly extract those spectroscopic signals, through a
      Spearman's rank correlation test (Spearman's correlation coefficient higher than
      0.981) performed between the original spectra and the ones obtained using those
      16 fabricated optical filters. These results are an important step for the
      implementation of a miniaturized, low-cost and minimal invasive microsystem that
      could help in the detection of gastrointestinal dysplasia. 

PMID- 26309771
TI  - Comparison of objective lenses for multiphoton microscopy in turbid samples.
AB  - Optimization of illumination and detection optics is pivotal for multiphoton
      imaging in highly scattering tissue and the objective lens is the central
      component in both of these pathways. To better understand how basic lens
      parameters (NA, magnification, field number) affect fluorescence collection and
      image quality, a two-detector setup was used with a specialized sample cell to
      separate measurement of total excitation from epifluorescence collection. Our
      data corroborate earlier findings that low-mag lenses can be superior at
      collecting scattered photons, and we compare a set of commonly used multiphoton
      objective lenses in terms of their ability to collect scattered fluorescence,
      providing guidance for the design of multiphoton imaging systems. For example,
      our measurements of epi-fluorescence beam divergence in the presence of
      scattering reveal minimal beam broadening, indicating that often-advocated over
      sized collection optics are not as advantageous as previously thought. These
      experiments also provide a framework for choosing objective lenses for
      multiphoton imaging by relating the results of our measurements to various design
      parameters of the objectives lenses used. 

PMID- 26309770
TI  - Clinical application of low-dose phase contrast breast CT: methods for the
      optimization of the reconstruction workflow.
AB  - Results are presented of a feasibility study of three-dimensional X-ray
      tomographic mammography utilising in-line phase contrast. Experiments were
      performed at SYRMEP beamline of Elettra synchrotron. A specially designed plastic
      phantom and a mastectomy sample containing a malignant lesion were used to study
      the reconstructed image quality as a function of different image processing
      operations. Detailed evaluation and optimization of image reconstruction
      workflows have been carried out using combinations of several advanced computed
      tomography algorithms with different pre-processing and post-processing steps.
      Special attention was paid to the effect of phase retrieval on the diagnostic
      value of the reconstructed images. A number of objective image quality indices
      have been applied for quantitative evaluation of the results, and these were
      compared with subjective assessments of the same images by three experienced
      radiologists and one pathologist. The outcomes of this study provide practical
      guidelines for the optimization of image processing workflows in synchrotron
      based phase-contrast mammo-tomography. 

PMID- 26309772
TI  - Carboxylic monolayer formation for observation of intracellular structures in
      HeLa cells with direct electron beam excitation-assisted fluorescence microscopy.
AB  - Intracellular structures of HeLa cells are observed using a direct electron beam
      excitation-assisted fluorescence (D-EXA) microscope. In this microscope, a
      silicon nitride membrane is used as a culture plate, which typically has a low
      biocompatibility between the sample and the silicon nitride surface to prevent
      the HeLa cells from adhering strongly to the surface. In this work, the surface
      of silicon nitride is modified to allow strong cell attachment, which enables
      high-resolution observation of intracellular structures and an increased signal
      to-noise ratio. In addition, the penetration depth of the electron beam is
      evaluated using Monte Carlo simulations. We can conclude from the results of the
      observations and simulations that the surface modification technique is promising
      for the observation of intracellular structures using the D-EXA microscope. 

PMID- 26309773
TI  - Subtle renal dysfunction and bleeding risk in atrial fibrillation: symmetric
      dimethylarginine predicts HAS-BLED score.
AB  - BACKGROUND: Risk of substantial haemorrhage represents a critically important
      limitation to effective anti-thrombotic treatment in patients with atrial
      fibrillation (AF). While it is known that this risk is increased in
      anticoagulated patients either in the presence of anti-aggregatory drugs or
      concomitant renal insufficiency, there are currently few data on the potential
      interactions between endogenous platelet aggregability and bleeding risk.
      OBJECTIVE: We therefore evaluated in a cohort of AF patients: (1), the putative
      relationship between platelet aggregability and HAS-BLED score; (2), the
      potential biochemical bases for such a relationship. METHODS: Patients were
      included as part of SAFETY, a randomised controlled trial evaluating outpatient
      management of AF patients. Platelet response to ADP was evaluated via whole blood
      impedance aggregometry; clinical and biochemical correlates of platelet
      aggregation were sought via univariate and multivariate analysis. RESULTS:
      Platelet aggregation correlated inversely (r=-0.220, p<0.05) with HAS-BLED score.
      Univariate biochemical correlates of decreased platelet aggregation were plasma
      concentrations of symmetric dimethylarginine (SDMA) and asymmetric
      dimethylarginine (ADMA). On multivariate analyses, plasma SDMA concentration
      (beta=-0.318, p<0.01), platelet content of thioredoxin-interacting protein
      (Txnip, beta=0.261, p<0.05) and plasma thrombospondin-1 (TSP-1, beta=0.249,
      p<0.05) concentration were predictive of platelet ADP response. Consistent with
      previous reports, plasma SDMA concentrations were strongly and inversely
      correlated with estimated glomerular filtration rate (eGFR, r=-0.780, p<0.001).
      CONCLUSIONS: These data therefore suggest that (1), physiologically impaired,
      like pharmacologically impaired, platelet aggregability may increase bleeding
      risk in anticoagulated AF patients; (2), the biochemical basis for this may
      include impaired effects of nitric oxide (via Txnip, TSP-1) but also concomitant
      renal dysfunction.

PMID- 26309774
TI  - Does the transapical approach impair early recovery of systolic strain following
      transcatheter aortic valve replacement?
AB  - BACKGROUND: In transcatheter aortic valve replacement (TAVR) the trans-apical
      approach (TA) is associated with apical myocardial injury but it is unknown if
      this injury impacts myocardial function. This study was performed to assess the
      impact of TA on apical longitudinal strain (ALS) and global longitudinal strain
      (GLS) after TAVR. METHODS: 44 consecutive patients (age 81 +/- 7 years, 48% male)
      underwent TAVR via trans-femoral (TF) (n=27) or TA (n=17) approach. Speckle
      tracking analysis of left ventricular longitudinal strain was performed on images
      from peri-procedure transesophageal echocardiograms immediately before and after
      valve implantation. The primary endpoint was a GLS improvement of at least 25%
      post-TAVR. RESULTS: GLS improved significantly above baseline after valve
      implantation in both TF (p<0.001) and TA (p=0.027) groups. The absolute
      magnitudes of ALS and GLS improvement were similar between TF and TA patients
      (ALS: p=0.282; GLS: p=0.248). Peak ALS and GLS achieved post-TAVR were similar
      between TF and TA patients (ALS: p=0.933; GLS: p=0.365). 47% of patients achieved
      a GLS improvement of >25%; 16 of which improved their GLS to <-15%. The severity
      of pre-TAVR GLS impairment was a strong independent predictor of GLS improvement
      (OR=1.61, p=0.003). A pre-TAVR GLS >=-13.7% was 82% sensitive and 82% specific
      for TAVR to confer a GLS improvement >25%. CONCLUSION: Equal improvement in
      myocardial strain was observed in the TF and TA patients. Pre-TAVR GLS impairment
      was an independent predictor of post-TAVR GLS recovery, highlighting how it is
      the patient's baseline GLS dysfunction, not the method of approach, that dictates
      post-TAVR functional recovery.

PMID- 26309775
TI  - Physiological adaptation of the left ventricle during the second and third
      trimesters of a healthy pregnancy: a speckle tracking echocardiography study.
AB  - BACKGROUND: During a healthy pregnancy women experience cardiovascular and
      hemodynamic changes and normal ranges of left ventricular (LV) function on two
      dimensional speckle tracking echocardiography (STE) are not well defined. The aim
      of this study was to describe the cardiovascular changes that occur during the
      second and third trimesters of a healthy pregnancy using STE. METHODS: Pregnant
      subjects were enrolled retrospectively if they underwent a transthoracic
      echocardiography (TTE) between 2011-2014. Subjects with abnormal TTE findings,
      hypertension, diabetes, preeclampsia, prior cardiac surgery, poor imaging quality
      or in the 1st trimester were excluded. A total of 74 pregnant subjects were
      categorized into the 2nd or 3rd trimesters. Twenty-one healthy age-matched
      females were selected as a control group. RESULTS: The heart undergoes extensive
      remodeling during pregnancy with increased LV septal thickness, posterior wall
      thickness, cavity size and mass (p=0.045, p=0.002, p<0.001, p=0.018,
      respectively). However, myocardial mechanical function measured by: global
      longitudinal strain, radial strain, circumferential strain, systolic and
      diastolic global longitudinal strain rate (GLSR), global radial strain rate
      (GRSR) and global circumferential strain rate, remains preserved. Only time to
      peak strain rate corrected for heart rate for diastolic GRSR and diastolic GLSR
      were significantly increased in the third trimester (p=0.016 for both).
      CONCLUSION: Despite extensive heart remodeling, many STE derived parameters of LV
      function in healthy pregnant women remain unchanged and valid for women in the
      2nd and 3rd trimester. Future studies investigating early detection of pregnancy
      related heart disease can refer to these parameters as reference ranges.

PMID- 26309776
TI  - Oxygen surrounding the heart during ischemic conservation determines the
      myocardial injury during reperfusion.
AB  - There is discrepancy regarding the duration of reperfusion required using 2,3,5
      triphenyl-2H-tetrazolium chloride (TTC) staining to assess myocardial infarction
      in an isolated, perfused heart model. Several investigators prefer long-term
      reperfusion (120 minutes) to determine myocardial injury, while others have used
      a shorter duration (30-40 minutes). We investigated whether oxygen surrounding
      the myocardium during ischemia plays a critical role in the installation of
      myocardial infarction during reperfusion. Mice hearts were perfused with a
      Langendorff apparatus using Krebs Henseleit (KH) buffer oxygenated with 95% O2
      plus 5% CO2 at 37 degrees C. Hearts were either immersed in KH or suspended in
      air during 18 minutes of global ischemia in a normothermic, water-jacketed
      chamber. Hearts then were reperfused for 40, 60, or 90 minutes. We found that
      hearts immersed in KH had decreased recovery of function and increased myocardial
      infarct size, reaching a steady-state level after 40 minutes of reperfusion. In
      contrast, hearts suspended in air approached steady-state after 90 minutes of
      reperfusion. Thus, mitochondrial reactive oxygen species (ROS) production was
      much lower in air-maintained hearts than in KH-immersed hearts. To investigate
      whether an increase in oxygen surrounding the myocardium during ischemia might
      cause further damage, we bubbled the KH solution with nitrogen (KH+N2) rather
      than oxygen (KH+O2). With this alteration, recovery of cardiac function was
      improved and myocardial infarct size and mitochondrial ROS production were
      reduced compared with hearts immersed in KH+O2. In conclusion, short-term (40
      minutes) reperfusion is sufficient to reach steady-state myocardial infarct size
      when hearts are immersed in physiologic solution during ischemia; however, a
      longer duration of reperfusion (90 minutes) is required if hearts are suspended
      in air. Thus, oxygen surrounding the heart during ischemia determines the extent
      of myocardium injury during reperfusion. 

PMID- 26309777
TI  - The contribution of opiate analgesics to the development of infectious
      complications in trauma patients.
AB  - Trauma-related pain is a natural consequence of injury and its surgical
      management; however, the relationship between opiates and complications in trauma
      patients is unknown. To study this a retrospective chart review of selected
      subjects following traumatic injury with admission to the SICU for > 3 days was
      performed, and opiate administration data was collected for the first 3 days of
      admission. Associated data from each subject's chart was also collected. Analysis
      of the data revealed that increased opiate intake after admission to the SICU was
      associated with significantly increased SICU and hospital LOS independent of
      injury severity. This increase in LOS was independent of mechanical ventilation
      in the moderate ISS group. Infectious complications were also more prevalent in
      the moderate ISS group with higher opiate use. These findings suggest that
      increased doses of opiate analgesics in trauma patients may contribute to an
      increased overall LOS and associated infectious complications. Analgesic regimes
      that minimize opiate intake, while still providing adequate pain relief, may be
      advantageous in reducing LOS, complications and reduce hospitalization costs. 

PMID- 26309778
TI  - Differential Effects of IFN-beta on the Survival and Growth of Human Vascular
      Smooth Muscle and Endothelial Cells.
AB  - It has been documented that interferon (IFN)-beta is effective against the
      genesis of atherosclerosis or hyperplastic arterial disease in animal model. The
      main mechanism of the efficacy was antiproliferative action on the growth of
      vascular smooth muscle cells (SMC). To understand more about the mechanisms that
      are responsible for the efficacy, we examined minutely the effects of IFN-beta on
      the apoptosis and growth of vascular SMC and endothelial cells (EC). IFN-beta
      enhanced SMC apoptosis in serum starved medium. Conversely, EC apoptosis induced
      by serum and growth factor deprivation was inhibited by IFN-beta. The induction
      of SMC apoptosis and anti-apoptotic effect on EC linked to the expression of pro
      apoptotic bax mRNA and caspase-3 activities. Anti-apoptotic bcl-2 mRNA was also
      up-regulated in EC. IFN-beta inhibited SMC growth in a dose dependent manner.
      However, the growth of EC was rather enhanced by a low dose of IFNs. The
      antiproliferative effect on SMC associated with the activation of p21 and
      increase of G0/G1 arrested cells. The growth stimulation on EC was considered to
      link with increase of S and G2/M phase cells. SMC produced IFN-beta in response
      to various stimulants. However, IFN-beta was not induced in EC. These suggested
      that endogenous IFN-beta from SMC may act on EC and affect to EC functions. In
      this study, it was clarified that IFN-beta enhances SMC apoptosis and inhibits
      the EC apoptosis, and stimulates the EC growth. These effects were considered to
      contribute to a cure against hyperplastic arterial diseases as the mechanisms in
      the efficacy of IFN-beta. 

PMID- 26309779
TI  - Determination of Cutoff Values for DEXA-Based Body Composition Measurements for
      Determining Metabolic and Cardiovascular Health.
AB  - The two components of the body weight (i.e., fat mass and muscle mass) appeared
      to be of high interest to consider in predicting metabolic health related risks.
      We aimed to determine cutoff values for fat mass index (FMI) and muscle mass
      index (MMI), FM/MM, and BMI for metabolic and cardiovascular health. This study
      was a cross-sectional analysis study conducted in a center of preventive
      medicine. It included 616 consecutive outpatients: mean age was 56.0+/-10.0 years
      (74.6% aged >=50), and 61.4% were female. Fat and muscle mass were obtained with
      dual energy X-ray absorptiometry scan analyses. Metabolically unhealthy
      individuals were defined as people with biological features of dyslipidemia,
      hyperuricemia, diabetes, and/or hepatitis steatosis. Documented hypertension
      and/or atherosclerosis of at least one major artery defined individuals with
      cardiovascular complications. Receiver-operating characteristic curve analysis
      revealed that the cutoff values for MMI, FMI, and FM/MM were respectively
      18.8kg/m(2) (sensitivity [Se]=58%; specificity [Sp]=59%), 5.5kg/m(2) (Se=61%;
      Sp=62%), and 0.31 (Se=62%; Sp=62%) in men; and 14.1kg/m(2) (Se=52%; Sp=54%),
      5.5kg/m(2) (Se=65%; Sp=67%), 0.39 (Se=73%; Sp=73%) in women for predicting
      metabolic health. Values were 19.3kg/m(2) (Se=58%; Sp=59%), 7.0kg/m(2) (Se=61%;
      Sp=62%) and 0.49 (Se=62%; Sp=62%) in men; and 15.7kg/m(2) (Se=58%; Sp=59%),
      6.4kg/m(2) (Se=61%; Sp=62%) and 0.35 (Se=62%; Sp=62%) in women for cardiovascular
      complications. Whatever the outcomes considered, the Youden indexes for BMI
      values were systematically below 25 kg/m(2), except for cardiovascular
      complications in men, where the threshold for the best Se/Sp was 25.7 kg/m(2).
      These cutoff values for FMI, MMI, and FM/MM could be of practical value for the
      clinical evaluation of a deficit in MM with or without excess of FM. They
      complement the classical concept of BMI in a more qualitative manner and extend
      the analysis of its impact on health outcomes to all BMI categories. 

PMID- 26309780
TI  - Autologous Stem Cell Therapy: How Aging and Chronic Diseases Affect Stem and
      Progenitor Cells.
AB  - During recent years different types of adult stem/progenitor cells have been
      successfully applied for the treatment of many pathologies, including
      cardiovascular diseases. The regenerative potential of these cells is considered
      to be due to their high proliferation and differentiation capacities, paracrine
      activity, and immunologic privilege. However, therapeutic efficacy of the
      autologous stem/progenitor cells for most clinical applications remains modest,
      possibly because of the attenuation of their regenerative potential in aged
      patients with chronic diseases such as cardiovascular diseases and metabolic
      disorders. In this review we will discuss the risk factors affecting the
      therapeutic potential of adult stem/progenitor cells as well as the main
      approaches to mitigating them using the methods of regenerative medicine. 

PMID- 26309781
TI  - beta1 Integrins Mediate Attachment of Mesenchymal Stem Cells to Cartilage
      Lesions.
AB  - Mesenchymal stem cells (MSC) may have great potential for cell-based therapies of
      osteoarthritis. However, after injection in the joint, only few cells adhere to
      defective articular cartilage and contribute to cartilage regeneration. Little is
      known about the molecular mechanisms of MSC attachment to defective articular
      cartilage. Here, we developed an ex vivo attachment system, using rat
      osteochondral explants with artificially created full-thickness cartilage defects
      in combination with genetically labeled MSC isolated from bone marrow of human
      placental alkaline phosphatase transgenic rats. Binding of MSC to full-thickness
      cartilage lesions was improved by serum, but not hyaluronic acid, and was
      dependent on the presence of divalent cations. Additional in vitro tests showed
      that rat MSC attach, in a divalent cation-dependent manner, to collagen I,
      collagen II, and fibronectin, but not to collagen XXII or cartilage oligomeric
      matrix protein (COMP). RGD peptides partially blocked the adhesion of MSC to
      fibronectin in vitro and to cartilage lesions ex vivo. Furthermore, the
      attachment of MSC to collagen I and II in vitro and to cartilage lesions ex vivo
      was almost completely abolished in the presence of a beta1 integrin blocking
      antibody. In conclusion, our data suggest that attachment of MSC to ex vivo full
      thickness cartilage lesions is almost entirely beta1 integrin-mediated, whereby
      both RGD- and collagen-binding integrins are involved. These findings suggest a
      key role of integrins during MSC attachment to defective cartilage and may pave
      the way for improved MSC-based therapies in the future. 

PMID- 26309782
TI  - Biological Effects Induced by Specific Advanced Glycation End Products in the
      Reconstructed Skin Model of Aging.
AB  - Advanced glycation end products (AGEs) accumulate in the aging skin. To
      understand the biological effects of individual AGEs, skin reconstructed with
      collagen selectively enriched with N(E)-(carboxymethyl)-lysine (CML), N(E)
      (carboxyethyl)-lysine (CEL), methylglyoxal hydroimidazolone (MG-H1), or
      pentosidine was studied. Immunohistochemistry revealed increased expression of
      alpha6 integrin at the dermal epidermal junction by CEL and CML (p<0.01). Laminin
      5 was diminished by CEL and MG-H1 (p<0.05). Both CML and CEL induced a robust
      increase (p<0.01) in procollagen I. In the culture medium, IL-6, VEGF, and MMP1
      secretion were significantly decreased (p<0.05) by MG-H1. While both CEL and CML
      decreased MMP3, only CEL decreased IL-6 and TIMP1, while CML stimulated TIMP1
      synthesis significantly (p<0.05). mRNA expression studies using qPCR in the
      epidermis layer showed that CEL increased type 7 collagen (COL7A1), beta1, and
      alpha6 integrin, while CML increased only COL7A1 (p<0.05). MG-H1-modified
      collagen had no effect. Importantly, in the dermis layer, MMP3 mRNA expression
      was increased by both CML and MG-H1. CML also significantly increased the mRNAs
      of MMP1, TIMP1, keratinocyte growth factor (KGF), IL-6, and monocyte
      chemoattractant protein 1 (MCP1) (p<0.05). Mixed effects were present in CEL-rich
      matrix. Minimally glycoxidized pentosidine-rich collagen suppressed most mRNAs of
      the genes studied (p<0.05) and decreased VEGF and increased MCP1 protein
      expression. Taken together, this model of the aging skin suggests that a
      combination of AGEs tends to counterbalance and thus minimizes the detrimental
      biological effects of individual AGEs. 

PMID- 26309783
TI  - Treating Proximal Tibial Growth Plate Injuries Using Poly(Lactic-co-Glycolic
      Acid) Scaffolds.
AB  - Growth plate fractures account for nearly 18.5% of fractures in children.
      Depending on the type and severity of the injury, inhibited bone growth or
      angular deformity caused by bone forming in place of the growth plate can occur.
      The current treatment involves removal of the bony bar and replacing it with a
      filler substance, such as a free fat graft. Unfortunately, reformation of the
      bony bar frequently occurs, preventing the native growth plate from regenerating.
      The goal of this pilot study was to determine whether biodegradable scaffolds can
      enhance native growth plate regeneration following a simulated injury that
      resulted in bony bar formation in the proximal tibial growth plate of New Zealand
      white rabbits. After removing the bony bar, animals received one of the following
      treatments: porous poly(lactic-co-glycolic acid) (PLGA) scaffold; PLGA scaffold
      loaded with insulin-like growth factor I (IGF-I); PLGA scaffold loaded with IGF-I
      and seeded with autogenous bone marrow cells (BMCs) harvested at the time of
      implantation; or fat graft (as used clinically). The PLGA scaffold group showed
      an increased chondrocyte population and a reduced loss of the remaining native
      growth plate compared to the fat graft group (the control group). An additional
      increase in chondrocyte density was seen in scaffolds loaded with IGF-I, and even
      more so when BMCs were seeded on the scaffold. While there was no significant
      reduction in the angular deformation of the limbs, the PLGA scaffolds increased
      the amount of cartilage and reduced the amount of bony bar reformation. 

PMID- 26309784
TI  - CD45+ Cells Present Within Mesenchymal Stem Cell Populations Affect Network
      Formation of Blood-Derived Endothelial Outgrowth Cells.
AB  - Mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) represent
      promising cell sources for angiogenic therapies. There are, however, conflicting
      reports regarding the ability of MSCs to support network formation of endothelial
      cells. The goal of this study was to assess the ability of human bone marrow
      derived MSCs to support network formation of endothelial outgrowth cells (EOCs)
      derived from umbilical cord blood EPCs. We hypothesized that upon in vitro
      coculture, MSCs and EOCs promote a microenvironment conducive for EOC network
      formation without the addition of angiogenic growth supplements. EOC networks
      formed by coculture with MSCs underwent regression and cell loss by day 10 with a
      near 4-fold and 2-fold reduction in branch points and mean segment length,
      respectively, in comparison with networks formed by coculture vascular smooth
      muscle cell (SMC) cocultures. EOC network regression in MSC cocultures was not
      caused by lack of vascular endothelial growth factor (VEGF)-A or changes in TGF
      beta1 or Ang-2 supernatant concentrations in comparison with SMC cocultures.
      Removal of CD45+ cells from MSCs improved EOC network formation through a 2-fold
      increase in total segment length and number of branch points in comparison to
      unsorted MSCs by day 6. These improvements, however, were not sustained by day
      10. CD45 expression in MSC cocultures correlated with EOC network regression with
      a 5-fold increase between day 6 and day 10 of culture. The addition of
      supplemental growth factors VEGF, fibroblastic growth factor-2, EGF,
      hydrocortisone, insulin growth factor-1, ascorbic acid, and heparin to MSC
      cocultures promoted stable EOC network formation over 2 weeks in vitro, without
      affecting CD45 expression, as evidenced by a lack of significant differences in
      total segment length (p=0.96). These findings demonstrate the ability of MSCs to
      support EOC network formation correlates with removal of CD45+ cells and improves
      upon the addition of soluble growth factors. 

PMID- 26309785
TI  - Enhanced Autophagy of Adipose-Derived Stem Cells Grown on Chitosan Substrates.
AB  - Autophagy is an important protein quality control mechanism for cells under
      stress conditions to promote cell survival. Modulation of autophagy on
      biomaterial substrates is rarely reported. In this study, the autophagy of
      adipose-derived stem cells (ADSCs) cultured on chitosan (CS) substrates was
      examined. Compared to the traditional monolayer culture, ADSCs cultured on CS
      substrates showed spheroid formation as well as a prolonged upregulation of
      autophagosomal marker-microtubule-associated protein 1 light chain 3 (LC3) II
      protein expression. In addition, the green fluorescent protein tagged-LC3 (GFP
      LC3) expressing ADSCs also revealed more GFP-LC3 puncta on CS substrates. The
      enhanced autophagy on CS substrates was associated with Ca(2+), while ethylene
      glycol tetraacetic acid (EGTA), a Ca(2+) chelator, repressed the autophagy in a
      dose-dependent manner. Moreover, ADSC spheroids on CS substrates demonstrated a
      higher survival rate and autophagy response upon H2O2 treatment. The upstream
      components of autophagy signal pathway-UNC51-like kinase 1 (Ulk1), autophagy
      related protein 13 (Atg13), and autophagy/beclin-1 regulator 1 (Ambra1) genes
      were more highly expressed in ADSC spheroids before and after adding H2O2 than
      those in the conventional culture. EGTA also decreased the cell viability and
      autophagy-associated gene expression for ADSC spheroids on CS substrates after
      H2O2 treatment. Therefore, we suggest that three-dimensional (3D) cell culture on
      CS may confer ADSCs the ability to increase the autophagic flux in response to
      stimulations in a Ca(2+)-dependent manner. 

PMID- 26309787
TI  - Gradient Fractionated Separation of Chondrogenically Committed Cells Derived from
      Human Embryonic Stem Cells.
AB  - Cartilage regeneration is a fast growing field that combines biotechnology and
      molecular techniques in creating new tissue mimicking the native
      microenvironment. Human embryonic stem cells (hESCs) are a highly potent cell
      source for cartilage regeneration owing to their infinite proliferation capacity
      and pluripotency. Thus, lineage-specific differentiation of hESCs often results
      in populations with cellular heterogeneity. Chondrogenesis was induced through
      high-density micromass culture of hESCs and by addition of chondrogenic medium;
      1:100 ITS(+), 100 nM dexamethasone, 40 MUg/ml l-proline, 50 MUg/mL ascorbic acid
      2-phosphate, 1:100 Knockout serum, and 10 ng/mL TGFbeta3. At day 14 micromasses
      were dissociated and chondrogenically committed cell separated in a fraction
      based discontinuous density gradient. After fractionation the chondrogenically
      committed cells were analyzed with regard to embryonic- and chondrogenic gene
      expression and fraction F3 and F4 with histology. In general, we found that the
      chondrogenic condition compared with the control condition had a significant
      effect on the following gene expression levels: NANOG, OCT4, SOX5, SOX9, ACAN,
      and COL2A1 in all fractions. Furthermore, we found in the chondrogenic condition
      that NANOG, OCT4, and SOX9 were significantly higher in F4 compared with F3,
      whereas COL2A1 and the ratio COL2A1:COL1A1 were significantly lower.
      Additionally, toluidine blue pH 4 stains of pellet cultures of F3 and F4 revealed
      that cells from F3 were more homogenous in morphology than F4. In conclusion, we
      propose a simple strategy to obtain more homogenous population of
      chondrogenically committed cells from hESCs using micromass culture and
      discontinuous density gradient separation. 

PMID- 26309786
TI  - Autophagy in Cancer Stem Cells: A Potential Link Between Chemoresistance,
      Recurrence, and Metastasis.
AB  - Cancer cells require an uninterrupted nutritional supply for maintaining their
      proliferative needs and this high demand in concurrence with inadequate supply of
      blood and nutrition induces stress in these cells. These cells utilize various
      strategies like high glycolytic flux, redox signaling, and modulation of
      autophagy to avoid cell death and overcome nutritional deficiency. Autophagy
      allows the cell to generate ATP and other essential biochemical building blocks
      necessary under such adverse conditions. It is emerging as a decisive process in
      the development and progression of pathophysiological conditions that are
      associated with increased cancer risk. However, the precise role of autophagy in
      tumorigenesis is still debatable. Autophagy is a novel cytoprotective process to
      augment tumor cell survival under nutrient or growth factor starvation, metabolic
      stress, and hypoxia. The tumor hypoxic environment may provide site for the
      enrichment/expansion of the cancer stem cells (CSCs) and successive rapid tumor
      progression. CSCs are characteristically resistant to conventional anticancer
      therapy, which may contribute to treatment failure and tumor relapse. CSCs have
      the potential to regenerate for an indefinite period, which can impel tumor
      metastatic invasion. From last decade, preclinical research has focused on the
      diversity in CSC content within tumors that could affect their chemo- or radio
      sensitivity by impeding with mechanisms of DNA repair and cell cycle progression.
      The aim of this review is predominantly directed on the recent developments in
      the CSCs during cancer treatment, role of autophagy in maintenance of CSC
      populations and their implications in the development of promising new cancer
      treatment options in future. 

PMID- 26309788
TI  - The APPEESFRS Peptide, Restricted by the HLA-B*35:01 Molecule, and the APPEESFRF
      Variant Derived from an Autologous HIV-1 Strain Induces Polyfunctional Responses
      in CD8+ T Cells.
AB  - Numerous reports have focused on consensus peptides to determine CD8+ T-cell
      responses; however, few studies evaluated the functional profile using peptides
      derived from circulating strains of a specific region. We determined the effector
      profile and maturation phenotype of CD8+ T-cells targeting the consensus
      APPEESFRS (AS9) epitope and its variant APPEESFRF (AF9), previously identified.
      The free energy of binding, maturation phenotype, and polyfunctional profile of
      both peptides were similar. The magnitude of CD8+ T-cell responses to AF9 was
      greater than the one elicited by AS9, although the difference was not
      significant. The polyfunctional profile of AF9 was characterized by
      CD107a/interleukin-2 (IL-2)/macrophage inflammatory protein beta (MIP1beta) and
      by interferon gamma (IFNgamma)/MIP1beta/tumor necrosis factor alpha (TNFalpha) in
      response to AS9. TNFalpha production was significantly higher in response to AF9
      than to AS9, and there was a negative correlation between the absolute number of
      CD8+ T-cell-producing TNFalpha and the plasma human immunodeficiency virus (HIV)
      load, suggesting a role of this cytokine in the control of HIV replication. 

PMID- 26309789
TI  - Induction of Osteogenic Differentiation in Human Mesenchymal Stem Cells by
      Crosstalk with Osteoblasts.
AB  - Natural bone healing following fractures is initiated by osteoblasts (OBs) and
      mesenchymal stem cells (MSCs), a cell combination with possible potential in
      tissue engineering techniques for bony defects. The aim of the study was to
      investigate MSC/OB-crosstalk, in order to determine optimal cell culture
      conditions for osteogenic differentiation. Human OBs and MSCs interactions were
      investigated in an in vitro trans-well co-culture study over a time period of 28
      days. Calcification was determined by optical density (OD) at 450 nm and Alizarin
      red staining. Messenger RNA expression was assessed by quantitative PCR.
      Osteogenic medium containing 1% fetal bovine serum resulted in superior levels of
      calcification in MSCs in co-culture with OBs compared to 2% or 5% fetal bovine
      serum (p<0.05). Comparing MSCs and OBs alone with the MSC/OB co-culture,
      calcification, as measured by OD 450 nm, increased over time in all groups. The
      highest values were recorded in the co-culture (p<0.05). Osteogenic
      differentiation potential showed significant interindividual differences. In
      order to predict differentiation potential, OD 450 nm measurements and mRNA
      expression of alkaline phosphatase were correlated with the population doubling
      rate during the expansion period. For OBs and MSCs, statistically significant
      associations of proliferation and differentiation potential were found (p<0.001).
      The addition of transforming growth factor beta resulted in up-regulation of
      collagen type I and Sp7 mRNA, and down-regulation of alkaline phosphatase mRNA.
      The results suggest the idea of soluble paracrine factors being secreted by OBs
      to induce osteogenic differentiation of MSCs. 

PMID- 26309790
TI  - Subcutaneous Adipose Tissue-Derived Stem Cell Utility Is Independent of
      Anatomical Harvest Site.
AB  - One of the challenges for tissue engineering and regenerative medicine is to
      obtain suitably large cell numbers for therapy. Mesenchymal stem cells (MSCs) can
      easily be expanded in vitro to obtain large numbers of cells, but this approach
      may induce cellular senescence. The characteristics of cells are dependent on
      variables like age, body mass index (BMI), and disease conditions, however, and
      in the case of adipose tissue-derived stem cells (ASCs), anatomical harvest site
      is also an important variable that can affect the regenerative potential of
      isolated cells. We therefore had kept the parameters (age, BMI, disease
      conditions) constant in this study to specifically assess influence of anatomical
      sites of individual donors on utility of ASCs. Adipose tissue was obtained from
      multiple anatomical sites in individual donors, and viability and nucleated cell
      yield were determined. MSC frequency was enumerated using colony forming unit
      assay and cells were characterized by flow cytometry. Growth characteristics were
      determined by long-term population doubling analysis of each sample. Finally,
      MSCs were induced to undergo adipogenic, osteogenic, and chondrogenic
      differentiation. To validate the findings, these results were compared with
      similar single harvest sites from multiple individual patients. The results of
      the current study indicated that MSCs obtained from multiple harvest sites in a
      single donor have similar morphology and phenotype. All adipose depots in a
      single donor exhibited similar MSC yield, viability, frequency, and growth
      characteristics. Equivalent differentiation capacity into osteocytes, adipocytes,
      and chondrocytes was also observed. On the basis of results, we conclude that it
      is acceptable to combine MSCs obtained from various anatomical locations in a
      single donor to obtain suitably large cell numbers required for therapy, avoiding
      in vitro senescence and lengthy and expensive in vitro culturing and expansion
      steps. 

PMID- 26309791
TI  - Effect of BDNF and Other Potential Survival Factors in Models of In Vitro
      Oxidative Stress on Adult Spinal Cord-Derived Neural Stem/Progenitor Cells.
AB  - Transplantation of neural stem/progenitor cells (NSPCs) is a promising strategy
      in spinal cord injury (SCI). However, poor survival of transplanted stem cells
      remains a major limitation of this therapy due to the hostile environment of the
      injured cord. Oxidative stress is a hallmark in the pathogenesis of SCI; however,
      its effects on NSPCs from the adult spinal cord have yet to be examined. We
      therefore developed in vitro models of mild and severe oxidative stress of adult
      spinal cord-derived NSPCs and used these models to examine potential cell
      survival factors. NSPCs harvested from the adult rat spinal cord were treated
      with hydrogen peroxide (H2O2) in vitro to induce oxidative stress. A mild 4 h
      exposure to H2O2 (500 MUM) significantly increased the level of intracellular
      reactive oxygen species with minimal effect on viability. In contrast, 24 h of
      oxidative stress led to a marked reduction in cell survival. Pretreatment with
      brain-derived neurotrophic factor (BDNF) for 48 h attenuated the increase in
      intracellular reactive oxygen species and enhanced survival. This survival effect
      was associated with a significant reduction in the number of apoptotic cells and
      a significant increase in the activity of the antioxidant enzymes glutathione
      reductase and superoxide dismutase. BDNF treatment had no effect on NSPC
      differentiation or proliferation. In contrast, cyclosporin A and thyrotropin
      releasing hormone had minimal or no effect on NSPC survival. Thus, these models
      of in vitro oxidative stress may be useful for screening neuroprotective factors
      administered prior to transplantation to enhance survival of stem cell
      transplants. 

PMID- 26309792
TI  - Serum Albumin Concentrations in a Multi-Ethnic Cohort of Patients with Human
      Immunodeficiency Virus Infection from South East London.
AB  - Human albumin is the most abundant protein in sera and a valuable biomarker in
      monitoring a variety of diseases. In this study we investigated the relationship
      between serum albumin concentrations and effects of initiation of highly active
      antiretroviral therapy (HAART). Serum albumin concentrations amongst 70 HIV
      infected patients from diverse ethnicities were analyzed, in the absence of any
      other confounding comorbidities, over a period of 8 years in South East London,
      United Kingdom. Serum albumin data was collected, on average, every 4-6 weeks
      during routine visits. Serum albumin was measured prior to starting HAART, and
      measured at the first clinic visit after commencing HAART. These were compared to
      a control group of untreated individuals. Based on our analyses we conclude that
      serum albumin concentrations increase significantly after the initiation of
      therapy. 

PMID- 26309793
TI  - Gene-Activated Matrix Comprised of Atelocollagen and Plasmid DNA Encoding BMP4 or
      Runx2 Promotes Rat Cranial Bone Augmentation.
AB  - To date, therapeutic method for in vivo gene delivery has not been established on
      bone engineering though its potential usefulness has been suggested. For clinical
      applications, an effective condition should be developed to transfer the genes in
      vivo without any transfection reagents or virus vectors. In this study, to
      facilitate the clinical setting of this strategy, particularly aimed at atrophic
      bone repair, we simply investigated whether manufactured gene-activated matrix
      (GAM) with atelocollagen containing a certain amount of plasmid (p) DNA encoding
      osteogenic proteins could augment the cranial bone in rat. GAMs were manufactured
      by mixing 0.02, 0.1, or 1 mg of AcGFP plasmid vectors harboring cDNA of BMP4
      (pBMP4) or Runx2 (pRunx2) with 2% bovine atelocollagen and beta-tricalcium
      phosphate granules. Before manufacturing GAMs, to determine the biological
      activity of generated pDNAs, we confirmed GFP expression and increased level of
      alkaline phosphatase activities in MC3T3-E1 cells transfected with pBMP4 or
      pRunx2 during culture. Then, GAMs were lyophilized and transplanted to onlay
      placement on the cranium. At 2 weeks of transplantation, GFP-expressing cells
      could be detectable in only GAMs containing 1 mg of AcGFP plasmid vectors. Then,
      at 4 weeks, significant bone formation was recognized in GAMs containing 1 mg of
      pDNAs encoding BMP4 or Runx2 but not in 0.02 or 0.1 mg of GAMs. These newly
      formed bone tissues surrounded by osteocalcin-stained area were augmented
      markedly until 8 weeks after transplantation. In contrast, minimal bone formation
      was observed in GAMs without harboring cDNA of osteogenic proteins. Meanwhile,
      when GAMs were transplanted to the cranial bone defect, bone formation was
      detectable in specimens containing 1 mg of pBMP4 or pRunx2 at 8 weeks as well.
      Thus, atelocollagen-based GAM reliably could form the engineered bone even for
      the vertical augmentation when containing a certain amount of plasmid vectors
      encoding osteogenic proteins. This study supports facilitating the clinical
      application of GAM for bone engineering. 

PMID- 26309794
TI  - Transient Exposure to Hypoxic and Anoxic Oxygen Concentrations Promotes Either
      Osteogenic or Ligamentogenic Characteristics of PDL Cells.
AB  - The periodontal ligament (PDL) has a reservoir of mesenchymal stem cells (MSCs)
      and this tissue is easily available following teeth removal procedures. However,
      PDL-derived cells (PDLCs) availability for tissue engineering is limited because
      they are heterogeneous cells at various differentiation and lineage commitments.
      Therefore, efficient culture conditions to increase MSCs number are needed to use
      PDLCs in tissue engineering. Recent reports indicate that low-oxygen conditions
      amplified stem/progenitor cell numbers and inhibited cell differentiation. Our
      aim was to establish which low-oxygen culture conditions favored bone or
      tendon/ligament regeneration in cultured PDLCs. Human PDLCs were cultured and
      exposed to either hypoxic (O2<=5%) or anoxic (O2<0.1%) oxygen conditions in low
      glucose/serum-free media for 24 hours. After 24 h, as expected, cell survival was
      significantly less in PDLCs exposed to anoxic conditions as compared with cells
      under normal or hypoxic conditions. PDLCs exposed to hypoxic conditions had the
      highest percentages for MSC markers (CD105, CD166, Stro-1). For both hypoxic and
      anoxic conditions, stem cell marker genes (oct4, sox2, p75) were upregulated
      after 6 h. At 24 h, these stem cell markers were maintained in PDLCs under
      hypoxic condition. Interestingly under anoxic conditions, expression of scleraxis
      gene (a key transcription factor for tendo/ligamentogenesis) was upregulated
      markedly. When hypoxic PDLCs were subcultured into osteogenic medium, in vitro
      calcification and prominent in vivo bone formation in mice calvaria were
      observed. When anoxic PDLCs were subcultured into tendo/ligamentogenic medium,
      expression of aggrecan (a mature tenogenic gene) increased remarkably. No obvious
      differences were detectable on chondrogenic and adipogenic inducibilities. We
      propose that transient exposure to low-oxygen during the culture enhanced MSC
      population in PDL. In addition, different low-oxygen concentrations favored
      osteogenic or tendo/ligamentogenic inducibilities of cultured PDLCs. 

PMID- 26309795
TI  - Development and Characterization of a Collagen-Based Matrix for Vascularization
      and Cell Delivery.
AB  - Since the development of the Edmonton protocol, islet transplantation is
      increasingly encouraging as a treatment for type 1 diabetes. Strategies to
      ameliorate problems with the intraportal site include macroencapsulating the
      islets in diverse biomaterials. Characterization of these biomaterials is
      important to optimally tune the properties to support islets and promote
      vascularization. In this study, we characterize the cross-linker-dependent
      properties of collagen-based matrices containing chondroitin-6-sulfate, chitosan,
      and laminin, cross-linked with 7.5, 30, or 120 mM of 1-ethyl-3-(3
      dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide. The swelling ratio
      was found to be significantly negatively correlated with increasing cross-linker
      concentrations (p<0.0001; R2=0.718). The matrix released insulin in a
      reproducible logarithmic manner (R2 of 0.99 for all concentrations),
      demonstrating cross-linker-dependent control of drug release. The matrices with
      the highest cross-linker concentrations resisted degradation by collagenase for
      longer than the lowest concentrations (58.13%+/-2.22% vs. 13.69%+/-7.67%;
      p<0.05). Scanning electron microscopy images of the matrices revealed that the
      matrices had uniform topography and porosity, indicating efficient cross-linking
      and incorporation of the polymer components. Matrices were transplanted
      subcutaneously in naive BALB/c mice, and the number and size of vessels were
      quantified using von Willebrand factor staining; matrices with higher cross
      linking concentrations had significantly larger capillaries at every time point
      up to 4 weeks after transplantation compared to the lowest cross-linker
      concentration group. CD31 staining visualized the capillaries at each time point.
      Taken together, these data show that this collagen-based matrix is reproducible
      with cross-linking-dependent properties that can be optimized to support
      vascularization and islet function. 

PMID- 26309796
TI  - An Autologous Muscle Tissue Expansion Approach for the Treatment of Volumetric
      Muscle Loss.
AB  - Volumetric muscle loss (VML) is a hallmark of orthopedic trauma with no current
      standard of care. As a potential therapy for some VML indications, autologous
      minced muscle grafts (1 mm(3) pieces of muscle) are effective in promoting
      remarkable de novo fiber regeneration. But they require ample donor muscle tissue
      and therefore may be limited in their application for large clinical VML. Here,
      we tested the hypothesis that autologous minced grafts may be volume expanded in
      a collagen hydrogel, allowing for the use of lesser autologous muscle while
      maintaining regenerative and functional efficacy. The results of the study
      indicate that 50% (but not 75%) less minced graft tissue suspended in a collagen
      hydrogel promoted a functional improvement similar to that of a 100% minced graft
      repair. However, approximately half of the number of fibers regenerated de novo
      with 50% graft repair. Moreover, the fibers that regenerated had a smaller cross
      sectional area. These findings support the concept of using autologous minced
      grafts for the regeneration of muscle tissue after VML, but indicate the need to
      identify optimal carrier materials for expansion. 

PMID- 26309797
TI  - Dissolved Gases and Ice Fracturing During the Freezing of a Multicellular
      Organism: Lessons from Tardigrades.
AB  - Three issues are critical for successful cryopreservation of multicellular
      material: gases dissolved in liquid, thermal conductivity of the tissue, and
      localization of microstructures. Here we show that heat distribution is
      controlled by the gas amount dissolved in liquids and that when changing the
      liquid into solid, the dissolved gases either form bubbles due to the absence of
      space in the lattice of solids and/or are migrated toward the concentrated salt
      and sugar solution at the cost of amount of heat required to be removed to
      complete a solid-state transition. These factors affect the heat distribution in
      the organs to be cryopreserved. We show that the gas concentration issue controls
      fracturing of ice when freezing. There are volumetric changes not only when
      changing the liquid into solid (volume increases) but also reduction of the
      volume when reaching lower temperatures (volume decreases). We discuss these
      issues parallel with observations of the cryosurvivability of multicellular
      organisms, tardigrades, and discuss their analogy for cryopreservation of large
      organs. 

PMID- 26309798
TI  - The First Scale-Up Production of Theranostic Nanoemulsions.
AB  - Theranostic nanomedicines are a promising new technological advancement toward
      personalized medicine. Although much progress has been made in pre-clinical
      studies, their clinical utilization is still under development. A key ingredient
      for successful theranostic clinical translation is pharmaceutical process design
      for production on a sufficient scale for clinical testing. In this study, we
      report, for the first time, a successful scale-up of a model theranostic
      nanoemulsion. Celecoxib-loaded near-infrared-labeled perfluorocarbon nanoemulsion
      was produced on three levels of scale (small at 54 mL, medium at 270 mL, and
      large at 1,000 mL) using microfluidization. The average size and polydispersity
      were not affected by the equipment used or production scale. The overall
      nanoemulsion stability was maintained for 90 days upon storage and was not
      impacted by nanoemulsion production scale or composition. Cell-based evaluations
      show comparable results for all nanoemulsions with no significant impact of
      nanoemulsion scale on cell toxicity and their pharmacological effects. This
      report serves as the first example of a successful scale-up of a theranostic
      nanoemulsion and a model for future studies on theranostic nanomedicine
      production and development. 

PMID- 26309799
TI  - Tissue Engineering Whole Bones Through Endochondral Ossification: Regenerating
      the Distal Phalanx.
AB  - Novel strategies are urgently required to facilitate regeneration of entire bones
      lost due to trauma or disease. In this study, we present a novel framework for
      the regeneration of whole bones by tissue engineering anatomically shaped
      hypertrophic cartilaginous grafts in vitro that subsequently drive endochondral
      bone formation in vivo. To realize this, we first fabricated molds from digitized
      images to generate mesenchymal stem cell-laden alginate hydrogels in the shape of
      different bones (the temporomandibular joint [TMJ] condyle and the distal
      phalanx). These constructs could be stimulated in vitro to generate anatomically
      shaped hypertrophic cartilaginous tissues that had begun to calcify around their
      periphery. Constructs were then formed into the shape of the distal phalanx to
      create the hypertrophic precursor of the osseous component of an engineered long
      bone. A layer of cartilage engineered through self-assembly of chondrocytes
      served as the articular surface of these constructs. Following chondrogenic
      priming and subcutaneous implantation, the hypertrophic phase of the engineered
      phalanx underwent endochondral ossification, leading to the generation of a
      vascularized bone integrated with a covering layer of stable articular cartilage.
      Furthermore, spatial bone deposition within the construct could be modulated by
      altering the architecture of the osseous component before implantation. These
      findings open up new horizons to whole limb regeneration by recapitulating key
      aspects of normal bone development. 

PMID- 26309800
TI  - Improved Human Pluripotent Stem Cell Attachment and Spreading on Xeno-Free
      Laminin-521-Coated Microcarriers Results in Efficient Growth in Agitated
      Cultures.
AB  - Human pluripotent stem cells (hPSC) are self-renewing cells having the potential
      of differentiation into the three lineages of somatic cells and thus can be
      medically used in diverse cellular therapies. One of the requirements for
      achieving these clinical applications is development of completely defined xeno
      free systems for large-scale cell expansion and differentiation. Previously, we
      demonstrated that microcarriers (MCs) coated with mouse laminin-111 (LN111) and
      positively charged poly-l-lysine (PLL) critically enable the formation and
      evolution of cells/MC aggregates with high cell yields obtained under agitated
      conditions. In this article, we further improved the MC system into a defined
      xeno-free MC one in which the MCs are coated with recombinant human laminin-521
      (LN521) alone without additional positive charge. The high binding affinity of
      the LN521 to cell integrins enables efficient initial HES-3 cell attachment (87%)
      and spreading (85%), which leads to generation of cells/MC aggregates (400 MUm in
      size) and high cell yields (2.4-3.5*10(6) cells/mL) within 7 days in agitated
      plate and scalable spinner cultures. The universality of the system was
      demonstrated by propagation of an induced pluripotent cells line in this defined
      MC system. Long-term pluripotent (>90% expression Tra-1-60) cell expansion and
      maintenance of normal karyotype was demonstrated after 10 cell passages.
      Moreover, tri-lineage differentiation as well as directed differentiation into
      cardiomyocytes was achieved. The new LN521-based MC system offers a defined, xeno
      free, GMP-compatible, and scalable bioprocessing platform for the production of
      hPSC with the quantity and quality compliant for clinical applications. Use of
      LN521 on MCs enabled a 34% savings in matrix and media costs over monolayer
      cultures to produce 10(8) cells. 

PMID- 26309801
TI  - Cryopreservation of In Vitro-Produced Early-Stage Porcine Embryos in a Closed
      System.
AB  - Cryostorage of porcine embryos in a closed pathogen-free system is essential for
      the maintenance and safeguard of swine models. Previously, we reported a protocol
      for the successful cryopreservation of porcine embryos at the blastocyst stage in
      0.25 mL ministraws. In this experiment, we aimed at developing a protocol to
      apply the same concept for the cryopreservation of early-stage porcine embryos.
      Porcine embryos from day 2 through day 4 were delipidated by using a modified two
      step centrifugation method and were then cryopreserved in sealed 0.25 mL straws
      by using a slow cooling method. Control groups included open pulled straw (OPS)
      vitrified embryos after delipidation and noncryopreserved embryos without
      delipidation. There were no significant differences in cryosurvival between
      embryos frozen in 0.25 mL straws and OPS vitrified embryos across all the stages
      (two cell to morula) examined (p>0.05). Similarly, in all groups examined, the
      blastocyst rates were not different between the two cryopreserved groups.
      However, the blastocyst rates from the cryopreserved groups were significantly
      lower than the noncryopreserved controls (p<0.05). This experiment demonstrated
      that early-stage porcine embryos can survive cryopreservation in a closed system
      by using a slow cooling method at a comparable rate to those vitrified by using
      an ultrarapid cooling method (p>0.05). However, the developmental competence was
      significantly reduced after cryopreservation compared to noncryopreserved
      embryos. Further research is needed to optimize the protocol to improve the
      developmental potential of cryopreserved early-stage porcine embryos in sealed
      straws. 

PMID- 26309802
TI  - Noninvasive Oxygen Monitoring in Three-Dimensional Tissue Cultures Under Static
      and Dynamic Culture Conditions.
AB  - We present a new method for noninvasive real-time oxygen measurement inside three
      dimensional tissue-engineered cell constructs in static and dynamic culture
      settings in a laminar flow bioreactor. The OPAL system (optical oxygen
      measurement system) determines the oxygen-dependent phosphorescence lifetime of
      spherical microprobes and uses a two-frequency phase-modulation technique, which
      fades out the interference of background fluorescence from the cell carrier and
      culture medium. Higher cell densities in the centrum of the scaffolds correlated
      with lower values of oxygen concentration obtained with the OPAL system. When
      scaffolds were placed in the bioreactor, higher oxygen values were measured
      compared to statically cultured scaffolds in a Petri dish, which were
      significantly different at day 1-3 of culture. This technique allows the use of
      signal-weak microprobes in biological environments and monitors the culture
      process inside a bioreactor. 

PMID- 26309803
TI  - Spraying Respiratory Epithelial Cells to Coat Tissue-Engineered Constructs.
AB  - Applying cells in a spray can overcome current hurdles in coating tissue
      engineered constructs with a thin layer of endo- or epithelial cells. We report
      here a structured study on the influences of spray application with a medical
      spray device on vascular smooth muscle cells (vSMCs) and respiratory epithelial
      cells (RECs) with and without fibrin gel. Next to viability and cytotoxicity
      assays, the in vitro differentiation capacity after spray processing was
      analyzed. For vSMC, no influence of air pressures till 0.8 bar could be shown,
      whereas the viability decreased for higher pressures. The viability of RECs was
      reduced to 88.5% with 0.4 bar air pressure. Lactate dehydrogenase-levels in the
      culture medium increased the first day after spraying but normalized afterward.
      In the short term, no differences by means of morphology and expression-specific
      markers for vSMCs and RECs were seen between the control and study group. In
      addition, in a long-term study for 28 days with the air-liquid interface, RECs
      differentiated and built up an organized epithelial layer with ciliary
      development that was comparable to the control for cells sprayed without fibrin
      gel. When spraying within fibrin gel, ciliary development was lower at 28 days.
      Thus, spraying of vSMCs and RECs was proved to be a suitable method for tissue
      engineering. Especially for RECs, this application is of special significance
      when coating luminal structures or other unfavorable topographies. 

PMID- 26309804
TI  - Human Mesenchymal Stem Cells Reendothelialize Porcine Heart Valve Scaffolds:
      Novel Perspectives in Heart Valve Tissue Engineering.
AB  - Heart valve diseases are usually treated by surgical intervention addressed for
      the replacement of the damaged valve with a biosynthetic or mechanical
      prosthesis. Although this approach guarantees a good quality of life for
      patients, it is not free from drawbacks (structural deterioration, nonstructural
      dysfunction, and reintervention). To overcome these limitations, the heart valve
      tissue engineering (HVTE) is developing new strategies to synthesize novel types
      of valve substitutes, by identifying efficient sources of both ideal scaffolds
      and cells. In particular, a natural matrix, able to interact with cellular
      components, appears to be a suitable solution. On the other hand, the well-known
      Wharton's jelly mesenchymal stem cells (WJ-MSCs) plasticity, regenerative
      abilities, and their immunomodulatory capacities make them highly promising for
      HVTE applications. In the present study, we investigated the possibility to use
      porcine valve matrix to regenerate in vitro the valve endothelium by WJ-MSCs
      differentiated along the endothelial lineage, paralleled with human umbilical
      vein endothelial cells (HUVECs), used as positive control. Here, we were able to
      successfully decellularize porcine heart valves, which were then recellularized
      with both differentiated-WJ-MSCs and HUVECs. Data demonstrated that both cell
      types were able to reconstitute a cellular monolayer. Cells were able to
      positively interact with the natural matrix and demonstrated the surface
      expression of typical endothelial markers. Altogether, these data suggest that
      the interaction between a biological scaffold and WJ-MSCs allows the regeneration
      of a morphologically well-structured endothelium, opening new perspectives in the
      field of HVTE. 

PMID- 26309805
TI  - Biomodification of PCL Scaffolds with Matrigel, HA, and SR1 Enhances De Novo
      Ectopic Bone Marrow Formation Induced by rhBMP-2.
AB  - The de novo formation of ectopic bone marrow was induced using 1.2-mm-thin
      polycaprolactone (PCL) scaffolds biomodified with several different biomaterials.
      In vivo investigations of de novo bone and bone marrow formation indicated that
      subcutaneous implantation of PCL scaffolds coated with recombinant human bone
      morphogenetic protein-2 (rhBMP-2) plus Matrigel, hydroxyapatite (HA), or
      StemRegenin 1 (SR1) improved formation of bone and hematopoietic bone marrow as
      determined by microcomputed tomography, and histological and hematopoietic
      characterizations. Our study provides evidence that thin PCL scaffolds
      biomodified with Matrigel, HA, and SR1 mimic the environments of real bone and
      bone marrow, thereby enhancing the de novo ectopic bone marrow formation induced
      by rhBMP-2. This ectopic bone marrow model will serve as a unique and essential
      tool for basic research and for clinical applications of postnatal tissue
      engineering and organ regeneration. 

PMID- 26309806
TI  - X-Ray-Induced Damage to the Submandibular Salivary Glands in Mice: An Analysis of
      Strain-Specific Responses.
AB  - Radiation therapy for head and neck cancers often causes xerostomia (dry mouth)
      by acutely damaging the salivary glands through the induction of severe acute
      inflammation. By contrast, the mechanism underlying the X-ray-induced delayed
      salivary dysfunction is unknown and has attracted increasing attention. To
      identify and develop a mouse model that distinguishes the delayed from the acute
      effects, we examined three different mouse strains (C57BL/6, ICR, and ICR-nu/nu)
      that showed distinct T-cell activities to comparatively analyze their responses
      to X-ray irradiation. Three strains were irradiated with X-rays (25 Gy), and
      functional changes of the submandibular glands were examined by determining
      pilocarpine-induced saliva secretion. Structural changes were evaluated using
      histopathological and immunohistochemical examinations of CD3, cleaved poly (ADP
      ribose) polymerase (PARP), and Bcl-xL. In C57BL/6 mice, the X-ray irradiation
      induced acute inflammation accompanied by severe inflammatory cell infiltration
      at 4 days postirradiation, causing substantial destruction and significant
      dysfunction at 2 weeks. Fibrotic repair was observed at 16 weeks. In ICR-nu/nu
      mice, the inflammation and organ destruction were much milder than in the other
      mice strains, but increased apoptotic cells and a significant reduction in
      salivary secretion were observed at 4 and 8 weeks and beyond, respectively. These
      results suggest that in C57BL/6 mice, X-ray-induced functional and structural
      damage to the salivary glands is caused mainly by acute inflammation. By
      contrast, although neither acute inflammation nor organ destruction was observed
      in ICR-nu/nu mice, apoptotic cell death preceded the dysfunction in salivary
      secretion in the later phase. These data suggest that the X-ray-irradiated ICR
      nu/nu mouse may be a useful animal model for developing more specific therapeutic
      methods for the delayed dysfunction of salivary glands. 

PMID- 26309807
TI  - The PTB-Associated Splicing Factor/Peroxisome Proliferator-Activated Receptor
      Gamma Axis Regulates Autophagosome Formation in Human Pancreatic Cancer Cells.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear
      receptor that plays a major regulatory role in metabolic function. It is
      overexpressed in many types of cancer cells, suggesting that regulation of
      PPARgamma may also affect carcinogenesis. Our previous study suggested that PTB
      associated splicing factor (PSF) is a PPARgamma-interacting protein and growth
      regulator of colon cancer cells. In addition, PSF has been shown to be involved
      in several important regulatory steps of cancer cell proliferation. In this
      study, we aimed to investigate the relationships between PSF and PPARgamma in
      pancreatic cancer by evaluating the effects of PSF expression in pancreatic
      cancer cell lines. PSF expression affected the expression of PPARgamma, and
      knockdown of PSF using specific small-interfering RNA (siRNA) significantly
      suppressed the proliferation of pancreatic cancer cells. Furthermore, PSF
      knockdown induced cell growth inhibition and autophagosome formation through
      inhibition of PPARgamma. Interestingly, Panc-1 cells were more susceptible to PSF
      knockdown-induced autophagy than MIA-PaCa-2 cells. Thus, our data indicated that
      PSF was an important regulator of autophagy and played critical roles in the
      survival and growth of pancreatic cancer cells. The PSF-PPARgamma axis may play a
      role in the control of pancreatic cancer pathogenesis. This study is the first to
      describe the effects of PSF on pancreatic cancer cell growth and autophagy
      associated with PPARgamma. 

PMID- 26309808
TI  - Potential Reparative Role of Resident Adult Renal Stem/Progenitor Cells in Acute
      Kidney Injury.
AB  - Human kidney is particularly susceptible to ischemia and toxins with
      consequential tubular necrosis and activation of inflammatory processes. This
      process can lead to the acute renal injury, and even if the kidney has a great
      capacity for regeneration after tubular damage, in several circumstances, the
      normal renal repair program may not be sufficient to achieve a successful
      regeneration. Resident adult renal stem/progenitor cells could participate in
      this repair process and have the potentiality to enhance the renal regenerative
      mechanism. This could be achieved both directly, by means of their capacity to
      differentiate and integrate into the renal tissues, and by means of paracrine
      factors able to induce or improve the renal repair or regeneration. Recent
      genetic fate-tracing studies indicated that tubular damage is instead repaired by
      proliferative duplication of epithelial cells, acquiring a transient progenitor
      phenotype and by fate-restricted clonal cell progeny emerging from different
      nephron segments. In this review, we discuss about the properties and the
      reparative characteristics of high regenerative CD133(+)/CD24(+) cells, with a
      view to a future application of these cells for the treatment of acute renal
      injury. 

PMID- 26309809
TI  - Reactive Oxygen Species and Mitochondrial DNA Damage and Repair in BCR-ABL1 Cells
      Resistant to Imatinib.
AB  - Imatinib revolutionized the therapy of chronic myeloid leukemia (CML), but the
      resistance to it became an emerging problem. We reported previously that CML
      cells expressing the BCR/ABL1 fusion gene, accumulated a high level of reactive
      oxygen species (ROS) due to deregulated mitochondrial electron transport chain,
      which in turn led to genomic instability, resulting in imatinib resistance. In
      the present work, we hypothesize that imatinib-resistant cells may show higher
      instability of mitochondrial DNA (mtDNA) than their sensitive counterparts. To
      verify this hypothesis, we checked the ROS level and mtDNA damage and repair in
      model CML cells sensitive and resistant to imatinib and exposed to doxorubicin
      (DOX), a DNA-damaging agent. The extent of endogenous ROS in imatinib-resistant
      cells was higher than in their sensitive counterparts and DOX potentiated this
      relationship. ROS level in cells with primary resistance, which resulted from the
      T315I mutation in BCR/ABL1, was higher than in cells with acquired resistance.
      DOX-induced mtDNA damage in T315I imatinib-resistant cells was more pronounced
      than in imatinib-sensitive cells. All kinds of cells were repairing mtDNA damage
      with similar kinetics. In conclusion, imatinib-resistant cells can show increased
      instability of mtDNA, which can result from increased ROS production. 

PMID- 26309810
TI  - A Scalable Perfusion Culture System with Miniature Peristaltic Pumps for Live
      Cell Imaging Assays with Provision for Microfabricated Scaffolds.
AB  - We present a perfusion culture system with miniature bioreactors and peristaltic
      pumps. The bioreactors are designed for perfusion, live-cell imaging studies,
      easy incorporation of microfabricated scaffolds, and convenience of operation in
      standard cell culture techniques. By combining with miniature peristaltic pumps
      one for each bioreactor to avoid cross-contamination and to maintain desired flow
      rate in each-we have made a culture system that facilitates perfusion culture
      inside standard incubators. This scalable system can support multiple parallel
      perfusion experiments. The major components are fabricated by three-dimensional
      printing using VeroWhite, which we show to be amenable to ex vivo cell culture.
      Furthermore, the components of the system can be reused, thus making it
      economical. We validate the system and illustrate its versatility by culturing
      primary rat hepatocytes, live imaging the growth of mouse fibroblasts (NIH 3T3)
      on microfabricated ring-scaffolds inserted into the bioreactor, performing
      perfusion culture of breast cancer cells (MCF7), and high-magnification imaging
      of hepatocarcinoma cells (HuH7). 

PMID- 26309812
TI  - Epigenetic Regulation of Apoptosis and Cell Cycle Regulatory Genes in Human Colon
      Carcinoma Cells.
AB  - 5-Fluorouracil (5-FU) is the standard chemotherapy for certain high risk stage 2
      and all stages 3 and 4 human colorectal cancer patients. However, patients often
      develop chemoresistance to 5-FU. We have identified verticillin A from
      Verticillium-infected wild mushrooms as a potent anti-cancer agent that
      effectively suppresses 5-FU-resistant human colon cancer cells. Interestingly, a
      sublethal dose of verticillin A also acts as a potent sensitizer that overcomes
      human colon carcinoma cell resistance to FasL- and TRAIL-induced apoptosis. To
      identify verticillin A-regulated genes, we performed a genome-wide gene
      expression analysis and identified 1287 genes whose expression levels were either
      up- or down-regulated 1.5 fold. Forty-six of these genes have known function in
      regulation of apoptosis, and ninety genes have function in cell cycle regulation.
      Our recent study has identified verticillin A as a selective histone
      methyltransferase inhibitor. These identified genes are thus potential molecular
      targets for epigenetic-based therapy to overcome human colon cancer 5-FU
      resistance. The entire dataset is deposited in the NIH GEO database. Accession
      number GSE51262.

PMID- 26309811
TI  - In silico model-based inference: an emerging approach for inverse problems in
      engineering better medicines.
AB  - Identifying the network of biochemical interactions that underpin disease
      pathophysiology is a key hurdle in drug discovery. While many components involved
      in these biological processes are identified, how components organize differently
      in health and disease remains unclear. In chemical engineering, mechanistic
      modeling provides a quantitative framework to capture our understanding of a
      reactive system and test this knowledge against data. Here, we describe an
      emerging approach to test this knowledge against data that leverages concepts
      from probability, Bayesian statistics, and chemical kinetics by focusing on two
      related inverse problems. The first problem is to identify the causal structure
      of the reaction network, given uncertainty as to how the reactive components
      interact. The second problem is to identify the values of the model parameters,
      when a network is known a priori.

PMID- 26309813
TI  - Neurotranscriptome profiles of multiple zebrafish strains.
AB  - Behavioral displays or physiological responses are often influenced by intrinsic
      and extrinsic mechanisms in the context of the organism's evolutionary history.
      Understanding differences in transcriptome profiles can give insight into
      adaptive or pathological responses. We utilize high throughput sequencing (RNA
      sequencing) to characterize the neurotranscriptome profiles in both males and
      females across four strains of zebrafish (Danio rerio). Strains varied by
      previously documented differences in stress and anxiety-like behavioral
      responses, and generations removed from wild-caught individuals. Here we describe
      detailed methodologies and quality controls in generating the raw RNA-sequencing
      reads that are publically available in NCBI's Gene Expression Omnibus database
      (GSE61108).

PMID- 26309814
TI  - Gestational Diabetes Associated with a Novel Mutation (378-379insTT) in the
      Glycerol Kinase Gene.
AB  - Glycerol kinase deficiency (GKD) is an X-linked inborn error of metabolism at the
      interface of fat and carbohydrate metabolism. We report a male patient with GKD
      and a novel insertion of TT in exon 5 at position 378 of the GK cDNA (378
      379insTT). This resulted in a premature stop codon and 0.8% normal GK activity.
      The mother is a carrier for this mutation and had gestational diabetes requiring
      insulin during this pregnancy but not in her previous pregnancy. Given the
      association between GKD and type 2 diabetes mellitus, it is interesting that the
      mother had gestational diabetes while carrying an affected fetus. Therefore, GKD
      is another disease where there may be a maternal-fetal interaction based on
      genotype. Further investigations may help elucidate the role of GKD in the
      carrier mother's gestational diabetes. In addition, these studies will provide
      better-informed counseling to families with GKD regarding the risk to carrier
      females.

PMID- 26309815
TI  - Impact of a novel homozygous mutation in nicotinamide nucleotide transhydrogenase
      on mitochondrial DNA integrity in a case of familial glucocorticoid deficiency.
AB  - BACKGROUND: Familial Glucocorticoid Deficiency (FGD) is a rare autosomal
      recessive disorder that is characterized by isolated glucocorticoid deficiency.
      Recently, mutations in the gene encoding for the mitochondrial nicotinamide
      nucleotide transhydrogenase (NNT) have been identified as a causative gene for
      FGD; however, no NNT activities have been reported in FGD patients carrying NNT
      mutations. METHODS: Clinical, biochemical and molecular analyses of lymphocytes
      from FDG homozygous and heterozygous carriers for the F215S NNT mutation.
      RESULTS: In this study, we described an FGD-affected Japanese patient carrying a
      novel NNT homozygous mutation (c.644T>C; F215S) with a significant loss-of
      function (NNT activity = 31% of healthy controls) in peripheral blood cells'
      mitochondria. The NNT activities of the parents, heterozygous for the mutation,
      were 61% of controls. CONCLUSIONS: Our results indicated that (i) mitochondrial
      biogenesis (citrate synthase activity) and/or mtDNA replication (mtDNA copy
      number) were affected at <=60% NNT activity because these parameters were
      affected in individuals carrying either one or both mutated alleles; and (ii)
      other outcomes (mtDNA deletions, protein tyrosine nitration, OXPHOS capacity)
      were affected at <=30% NNT activity as also observed in murine cerebellar
      mitochondria from C57BL/6J (NNT-/-) vs. C57BL/6JN (NNT+/+) substrains. GENERAL
      SIGNIFICANCE: By studying a family affected with a novel point mutation in the
      NNT gene, a gene-dose response was found for various mitochondrial outcomes
      providing for novel insights into the role of NNT in the maintenance of mtDNA
      integrity beyond that described for preventing oxidative stress.

PMID- 26309816
TI  - Interferon-gamma: Promising therapeutic target in atherosclerosis.
AB  - Atherosclerosis is a chronic inflammatory disorder of the vasculature and is the
      primary cause of cardiovascular disease (CVD). CVD is currently the world's
      leading cause of death and the numbers are predicted to rise further because of a
      global increase in risk factors such as diabetes and obesity. Current therapies
      such as statins have had a major impact in reducing mortality from CVD. However,
      there is a marked residual CVD risk in patients on statin therapy. It is
      therefore important to understand the molecular basis of this disease in detail
      and to develop alternative novel therapeutics. Interferon-gamma (IFN-gamma) is a
      pro-inflammatory cytokine that is often regarded as a master regulator of
      atherosclerosis development. IFN-gamma is able to influence several key steps
      during atherosclerosis development, including pro-inflammatory gene expression,
      the recruitment of monocytes from the blood to the activated arterial endothelium
      and plaque stability. This central role of IFN-gamma makes it a promising
      therapeutic target. The purpose of this editorial is to describe the key role IFN
      gamma plays during atherosclerosis development, as well as discuss potential
      strategies to target it therapeutically. 

PMID- 26309817
TI  - Eurytrematosis: An emerging and neglected disease in South Brazil.
AB  - The trematodes of the genus Eurytrema are low pathogenic pancreatic parasites,
      but can be related to a decrease in cattle productive performance and eventually
      death. Parasitized animals develop chronic interstitial pancreatitis and may show
      a productive performance drop and emaciation. Human infection by Eurytrema sp.
      has already been reported in other countries as an incidental finding during
      autopsy or routine tests, but the parasite has not been found in humans in
      Brazil. However, it is possible that a large number of people could be infected,
      since parasitological tests have low sensitivity and the parasite is neglected as
      a pathogen for humans and even animals. Attempts to control and treat
      Eurytrematosis have generally presented low effectiveness. With the aim to
      control the disease and provide more information regarding its pathogenicity, our
      research group is developing a number of studies about Eurytrema spp. We hope to
      determine the damage in productivity, as well as, establish an efficient protocol
      for treatment and control of Eurytrematosis based on immunoprophylaxis and
      antiparasitical drug therapy. 

PMID- 26309820
TI  - Multiplex planar microarrays for disease prognosis, diagnosis and theranosis.
AB  - Advanced diagnostic methods and algorithms for immune disorders provide
      qualitative and quantitative multiplex measurement for pre-clinical prognostic
      and clinical diagnostic biomarkers specific for diseases. Choice of therapy is
      confirmed by modulating diagnostic efficacy of companion, theranotic drug
      concentrations. Assay methods identify, monitor and manage autoimmune diseases,
      or risk thereof, in subjects who have, or who are related to individuals with
      autoimmune disease. These same diagnostic protocols also integrate qualitative
      and quantitative assay test protocol designs for responder patient assessment,
      risk analysis and management of disease when integrating multiplex planar
      microarray diagnostic tests, patient theranostic companion diagnostic methods and
      test panels for simultaneous assessment and management of dysimmune and
      inflammatory disorders, autoimmunity, allergy and cancer. Proprietary assay
      methods are provided to identify, monitor and manage dysimmune conditions, or
      risk thereof, in subjects with pathological alterations in the immune system, or
      who are related to individuals with these conditions. The protocols can be used
      for confirmatory testing of subjects who exhibit symptoms of dysimmunity, as well
      as subjects who are apparently healthy and do not exhibit symptoms of altered
      immune function. The protocols also provide for methods of determining whether a
      subject has, is at risk for, or is a candidate for disease therapy, guided by
      companion diagnosis and immunosuppressive therapy, as well as therapeutic drug
      monitoring and theranostic testing of disease biomarkers in response to immuno
      absorption therapy. The multiplex test panels provide the components that are
      integral for performing the methods to recognized clinical standards. 

PMID- 26309819
TI  - Computed tomography-based finite element analysis to assess fracture risk and
      osteoporosis treatment.
AB  - Finite element analysis (FEA) is a computer technique of structural stress
      analysis and developed in engineering mechanics. FEA has developed to investigate
      structural behavior of human bones over the past 40 years. When the faster
      computers have acquired, better FEA, using 3-dimensional computed tomography (CT)
      has been developed. This CT-based finite element analysis (CT/FEA) has provided
      clinicians with useful data. In this review, the mechanism of CT/FEA, validation
      studies of CT/FEA to evaluate accuracy and reliability in human bones, and
      clinical application studies to assess fracture risk and effects of osteoporosis
      medication are overviewed. 

PMID- 26309821
TI  - Eribulin for heavily pre-treated metastatic breast cancer patients.
AB  - AIM: To discuss treatment with eribulin in clinical practice outside a clinical
      trial. METHODS: Archives of patients treated for metastatic breast cancer were
      reviewed and 21 patients treated with the new chemotherapeutic eribulin mesylate,
      a synthetic analog of a natural marine product, were identified. Information on
      patients' characteristics and treatment outcomes was extracted. Treatment with
      eribulin mesylate was initiated at the recommended dose of 1.4 mg/m(2) on days 1
      and 8 of a 21-day cycle in 17 patients and at a decreased dose of 1.1 mg/m(2) on
      days 1 and 8 of a 21-day cycle in 4 patients due to comorbidities and frailty.
      Efficacy of the drug was evaluated using the revised Response Evaluation Criteria
      in Solid Tumors criteria. Progression-Free Survival and overall survival (OS)
      were calculated using the Kaplan-Meier method starting from the date of eribulin
      therapy initiation to the date of disease progression documentation or death,
      respectively. RESULTS: The median age of patients at the time of eribulin
      mesylate treatment was 53 years (range 34-75). Sixteen patients had estrogen
      receptor (ER) and/or partial response (PR) positive disease and 5 had ER/PR
      negative disease (all triple negative). Eight patients had received 2 or 3
      previous lines of chemotherapy for metastatic disease and 13 patients had
      received 4 or more lines of treatment. The median number of cycles of eribulin
      received was 3 (range 1-16 years). All patients, except one, discontinued
      treatment due to progressive disease and one patient due to adverse effects. Six
      patients had a dose reduction due to side effects. All patients had progressed at
      the time of the report with a median time to progression of 3 mo (range 1 to 14
      mo). Fifteen patients had died with a median OS of 7 mo (range 1-18 mo). Six
      patients were alive with a median follow-up of 13.5 mo (range 7 to 19 mo).
      CONCLUSION: This series of patients confirms the activity of eribulin in a
      heavily pre-treated metastatic breast cancer population consistent with phase II
      and III trials.

PMID- 26309822
TI  - Mitral valve repair.

PMID- 26309818
TI  - Use of siRNA molecular beacons to detect and attenuate mycobacterial infection in
      macrophages.
AB  - Tuberculosis is one of the leading infectious diseases plaguing mankind and is
      mediated by the facultative pathogen, Mycobacterium tuberculosis (MTB). Once the
      pathogen enters the body, it subverts the host immune defenses and thrives for
      extended periods of time within the host macrophages in the lung granulomas, a
      condition called latent tuberculosis (LTB). Persons with LTB are prone to
      reactivation of the disease when the body's immunity is compromised. Currently
      there are no reliable and effective diagnosis and treatment options for LTB,
      which necessitates new research in this area. The mycobacterial proteins and
      genes mediating the adaptive responses inside the macrophage is largely yet to be
      determined. Recently, it has been shown that the mce operon genes are critical
      for host cell invasion by the mycobacterium and for establishing a persistent
      infection in both in vitro and in mouse models of tuberculosis. The YrbE and Mce
      proteins which are encoded by the MTB mce operons display high degrees of
      homology to the permeases and the surface binding protein of the ABC transports,
      respectively. Similarities in structure and cell surface location impute a role
      in cell invasion at cholesterol rich regions and immunomodulation. The mce4
      operon is also thought to encode a cholesterol transport system that enables the
      mycobacterium to derive both energy and carbon from the host membrane lipids and
      possibly generating virulence mediating metabolites, thus enabling the bacteria
      in its long term survival within the granuloma. Various deletion mutation studies
      involving individual or whole mce operon genes have shown to be conferring
      varying degrees of attenuation of infectivity or at times hypervirulence to the
      host MTB, with the deletion of mce4A operon gene conferring the greatest degree
      of attenuation of virulence. Antisense technology using synthetic siRNAs has been
      used in knocking down genes in bacteria and over the years this has evolved into
      a powerful tool for elucidating the roles of various genes mediating infectivity
      and survival in mycobacteria. Molecular beacons are a newer class of antisense
      RNA tagged with a fluorophore/quencher pair and their use for in vivo detection
      and knockdown of mRNA is rapidly gaining popularity.

PMID- 26309823
TI  - Early surgical intervention or watchful waiting for the management of
      asymptomatic mitral regurgitation: a systematic review and meta-analysis.
AB  - BACKGROUND: Discordance between studies drives continued debate regarding the
      best management of asymptomatic severe mitral regurgitation (MR). The aim of the
      present study was to conduct a systematic review and meta-analysis of management
      plans for asymptomatic severe MR, and compare the effectiveness of a strategy of
      early surgery to watchful waiting. METHODS: A systematic review was performed
      using the Preferred Reporting Items for Systematic Reviews and Meta-analyses
      (PRISMA) guidelines. Studies were excluded if they: (I) lacked a watchful waiting
      cohort; (II) included symptomatic patients; or (III) included etiologies other
      than degenerative mitral valve disease. The primary outcome of the study was all
      cause mortality at 10 years. Secondary outcomes included operative mortality,
      repair rate, repeat mitral valve surgery, and development of new atrial
      fibrillation. RESULTS: Five observational studies were eligible for review and
      three were included in the pooled analysis. In asymptomatic patients without
      class I triggers (symptoms or ventricular dysfunction), pooled analysis revealed
      a significant reduction in long-term mortality with an early surgery approach
      [hazard ratio (HR) =0.38; 95% confidence interval (CI): 0.21-0.71]. This survival
      benefit persisted in a sub-group analysis limited to patients without class II
      triggers (atrial fibrillation or pulmonary hypertension) [relative risk (RR)
      =0.85; 95% CI: 0.75-0.98]. Aggregate rates of operative mortality did not differ
      between treatment arms (0.7% vs. 0.7% for early surgery vs. watchful waiting).
      However, significantly higher repair rates were achieved in the early surgery
      cohorts (RR =1.10; 95% CI: 1.02-1.18). CONCLUSIONS: Despite disagreement between
      individual studies, the present meta-analysis demonstrates that a strategy of
      early surgery may improve survival and increase the likelihood of mitral valve
      repair compared with watchful waiting. Early surgery may also benefit patients
      when instituted prior to the development of class II triggers.

PMID- 26309824
TI  - Mitral valve repair versus replacement.
AB  - Degenerative, ischemic, rheumatic and infectious (endocarditis) processes are
      responsible for mitral valve disease in adults. Mitral valve repair has been
      widely regarded as the optimal surgical procedure to treat mitral valve
      dysfunction of all etiologies. The supporting evidence for repair over
      replacement is strongest in degenerative mitral regurgitation. The aim of the
      present review is to summarize the data in each category of mitral insufficiency
      and to provide recommendations based upon this data. 

PMID- 26309825
TI  - Posterior annulus shortening increases leaflet coaptation in ischemic mitral
      incompetence: a new and valid technique.
AB  - BACKGROUND: We introduce a technique of posterior annulus shortening to augment
      leaflet coaptation which addresses the restrictive mitral leaflet mobility in
      ischemic mitral incompetence (IMI), and report its long-term outcome. METHODS:
      Between 1992 and 2012, 75 patients (mean age, 64.6+/-10.4 years; median, 66.0
      years; range, 35.0-86.1 years) underwent repair of IMI by posterior annulus
      shortening to augment leaflet coaptation surface area. This technique reduces the
      annular diameter to between 23 and 25 mm and decreases the valve orifice to
      between 3.5 to 4.5 cm(2), which is sufficient to ensure an adequate leaflet
      coaptation area. An untreated pericardial strip is used to reinforce the
      shortened annulus in order to avoid redilatation. This augments the posterior
      leaflet by increasing the ratio of leaflet area/valve orifice where the
      coaptation gap is the greatest. The tissue strip increases and heightens the area
      which the posterior leaflet offers to the anterior leaflet for coaptation during
      closure, making valve closure possible in advanced leaflet restriction. RESULTS:
      During a mean follow-up of 7.62+/-0.66 (median 8.53, range, 3.6-20.9) years, New
      York Heart Association (NYHA) functional class significantly improved, left
      ventricular ejection fraction (LVEF) increased and there was a tremendous
      abatement of MI (P<0.01). Annular area was reduced from 9.2 to 5.8 cm(2).
      Coaptation area was increased from a complete lack thereof to 6.6 mm(2) post
      repair. CT showed posterior annulus size reduction from 70.4 to 54 mm and an
      increase in posterior leaflet length from 15.9 to 19.6 mm. A remarkable CT
      finding was the increase in coaptation length from 5.2 to 8.2 mm. Eighteen-year
      freedom from moderate MI, freedom from reoperation and survival rates were
      80.7%+/-9%, 84.9%+/-4.2% and 65.1%+/-6.3%, respectively. CONCLUSIONS: Posterior
      annulus shortening with pericardial strip augmentation addressing the lack of
      leaflet coaptation is a simple, reproducible and highly effective technique to
      restore valve competence in IMI.

PMID- 26309827
TI  - Ventricular apical access and closure, and re-access devices to facilitate mitral
      valve interventions.

PMID- 26309826
TI  - Lifting posterior mitral annuloplasty for enhancing leaflet coaptation in mitral
      valve repair: midterm outcomes.
AB  - BACKGROUND: We evaluated the midterm outcomes of lifting posterior mitral
      annuloplasty for enhancing leaflet coaptation in mitral valve repair. METHODS:
      Between October 2007 and December 2012, 341 consecutive patients with significant
      mitral regurgitation underwent lifting posterior mitral annuloplasty using a
      specially designed fabric annuloplasty strip that lifts the middle portion of the
      posterior annulus. Associated procedures for mitral valve repairs, such as patch
      valvuloplasty for posterior leaflet prolapse (n=80), new chord placement for
      anterior leaflet prolapse (n=33), commissurotomy (n=29), and posterior leaflet
      extension (n=23), were performed in 141 patients (41.3%). RESULTS: Thirty-day
      mortality was 0.9%. Nine late deaths (2.6%) occurred. Mean overall survival at 5
      years was 96.0%+/-1.1%. During the mean follow-up period of 38+/-17 months, six
      patients (1.8%) underwent valve-related reoperation (5-year freedom from valve
      related reoperation, 98.1%+/-0.8%). At 5 years, mean freedom from recurrence of
      mitral regurgitation grade 3+ to 4+ (moderate to severe) was 95.1%+/-1.6%. The
      mean valve pressure gradient (PG) was 3.2+/-1.5 mmHg across all strip sizes at
      the time of follow-up. CONCLUSIONS: Lifting posterior mitral annuloplasty using
      an innovative annuloplasty strip in mitral valve repair has a low rate of
      recurrent regurgitation or valve-related reoperation with rare relevant
      complications.

PMID- 26309828
TI  - The choice of mitral annuloplastic ring-beyond "surgeon's preference".

PMID- 26309829
TI  - Repair or observe moderate ischemic mitral regurgitation during coronary artery
      bypass grafting? Prospective randomized multicenter data.
AB  - Ischemic mitral regurgitation (MR) is a common occurrence following myocardial
      infarction and its presence is associated with poor outcomes. The optimal
      treatment of ischemic MR is a matter of debate, especially for patients with
      moderate MR severity. Some authors advocate for isolated coronary artery bypass
      grafting (CABG) for patients with moderate MR, maintaining that reverse
      ventricular remodeling will reduce MR grade and its associated mortality risk,
      while others argue that a concomitant mitral valve repair (MVR) or replacement is
      superior. The Cardiothoracic Surgical Trials Network (CTSN) recently published
      the 1-year results of the Surgical Treatment of Moderate Ischemic Mitral
      Regurgitation study, a multicenter, randomized, controlled trial investigating
      the impact of MVR in addition to CABG compared to CABG alone in the treatment of
      moderate ischemic MR. Here, we have reviewed previous observational and
      prospective studies investigating moderate ischemic MR treatment as well as the
      results of the current CTSN randomized trial. Furthermore, we have summarized the
      current state of the available evidence and preview potential new information
      that will become available with planned subgroup analyses and further follow-up
      of enrolled patients in the recently completed CTSN trial. 

PMID- 26309830
TI  - Prolapse of the posterior leaflet: resect or respect.
AB  - Prolapse of the posterior leaflet (PPL) is the most frequent dysfunction of the
      mitral valve in the western world. Quadrangular resection, first proposed by
      Alain Carpentier, has progressed to become the gold standard modality to repair
      posterior leaflet prolapse. Although this "resection technique" is safe,
      reproducible, and offers favorable long term results, it presents major
      drawbacks. Firstly, it leads to a reduced surface of coaptation, the ultimate
      goal of mitral valve repair; secondly, it does not respect the anatomy of the
      mitral valve; thirdly, it leads to a deformation of the base of the ventricle;
      and finally, degenerative disease of the mitral valve is a spectrum of lesions
      depending on the amount of excess tissue, and hence, a one technique-fits-all
      strategy cannot meet the absolute necessity to repair all mitral valve patients
      with PPL. Therefore, new approaches which have been proposed place greater
      emphasis on respecting, rather than only resecting, the leaflet tissue in order
      to avoid the drawbacks of the "resection" approach. The use of artificial chordae
      to correct the leaflet prolapse restores the normal anatomy and physiology of the
      mitral valve, thus producing an optimal surface of coaptation. However, this
      approach is limited by anatomical variances. As a community, we should expand our
      vision and define a clear and helpful strategy for PPL: to obtain a high, smooth
      and regular surface of coaptation located in the inflow of the left ventricle. To
      achieve this goal, it is necessary to have a high level of respect for the
      leaflet tissue in order to obtain the best surface of coaptation. Nonetheless, a
      limited resection may be needed to remodel the posterior leaflet, so that it will
      be smooth and regular. 

PMID- 26309831
TI  - Catheter-based or surgical repair of the highest risk secondary mitral
      regurgitation patients.
AB  - Surgical mitral valve repair (MVR) remains the standard of care for patients with
      severe valve incompetence with clear, proven benefit for patients with primary
      mitral regurgitation (MR). Secondary MR is a primary disease of the left
      ventricular (LV) myocardium. Up to 50% of patients develop secondary MR after an
      acute myocardial infarction (ischemic MR), with approximately 10% of these having
      severe MR. It is controversial as to whether surgical MVR is beneficial for these
      patients because valve repair or replacement does not correct the underlying
      disease. The increased perioperative risk due to decreased LV function makes
      clinical decision-making even more complex. The recently introduced less
      invasive, catheter-based therapies are potential promising solutions for this
      dilemma. While the MitraClip device is already in widespread clinical use as a
      viable therapeutic option in higher-risk patients with primary MR and currently
      in investigational trials for secondary MR, several other devices for both repair
      and replacement are currently undergoing feasibility trials. Due to the complex
      structure of the mitral valve, the development of transcatheter mitral valve
      replacement has been much slower than that of transcatheter aortic valve
      replacement, but this approach may be an attractive therapeutic option in the
      future. Currently, the role of surgical therapy in comparison to transcatheter
      techniques in secondary MR is not well defined. 

PMID- 26309832
TI  - Mitral valve repair for ischemic mitral regurgitation.
AB  - Mitral valve repair for ischemic mitral valve regurgitation remains
      controversial. In moderate mitral regurgitation (MR), controversy exists whether
      revascularization alone will be adequate to restore native valve geometry or
      whether intervention on the valve (repair) should be performed concomitantly.
      When MR is severe, the need for valve intervention is not disputed. Rather, the
      controversy is whether repair versus replacement should be undertaken. In
      contrast to degenerative or myxomatous disease that directly affects leaflet
      integrity and morphology, ischemic FMR results from a distortion and dilation of
      native ventricular geometry that normally supports normal leaflet coaptation. To
      address this, the first and most crucial step in successful valve repair is
      placement of an undersized, complete remodeling annuloplasty ring to restore the
      annulus to its native geometry. The following article outlines the steps for
      repair of ischemic mitral regurgitation. 

PMID- 26309833
TI  - Mitral valve repair with neo-chordae.

PMID- 26309834
TI  - Off-pump transapical neo-chordae implantation.

PMID- 26309835
TI  - Transapical off-pump mitral valve repair with Neochord Implantation (TOP-MINI):
      step-by-step guide.

PMID- 26309836
TI  - Minimally invasive mitral valve repair using a semi-rigid annuloplasty ring with
      a new chordal sizing system: the Memo3D ReChord.

PMID- 26309837
TI  - Leaflet extension for repairing rheumatic mitral valve regurgitation.

PMID- 26309838
TI  - Minimally invasive mitral valve surgery.

PMID- 26309839
TI  - A meta-analysis of robotic vs. conventional mitral valve surgery.
AB  - OBJECTIVES: The present study is the first meta-analysis to compare the surgical
      outcomes of robotic vs. conventional mitral valve surgery in patients with
      degenerative mitral valve disease. METHODS: A systematic review of the literature
      was conducted to identify all relevant studies with comparative data on robotic
      vs. conventional mitral valve surgery. Predefined primary endpoints included
      mortality, stroke and reoperation for bleeding. Secondary endpoints included
      cross-clamp time, cardiopulmonary bypass time, length of hospitalization and
      duration of intensive care unit (ICU) stay. Echocardiographic outcomes were
      assessed when possible. RESULTS: Six relevant retrospective studies with
      comparative data for robotic vs. conventional mitral valve surgery were
      identified from the existing literature. Meta-analysis demonstrated a superior
      perioperative survival outcome for patients who underwent robotic surgery.
      Incidences of stroke and reoperation were not statistically different between the
      two treatment arms. Patients who underwent robotic surgery required a
      significantly longer period of cardiopulmonary bypass time and cross-clamp time.
      However, the lengths of hospitalization and ICU stay were not significantly
      different. Both surgical techniques appeared to achieve satisfactory
      echocardiographic outcomes in the majority of patients. CONCLUSIONS: Current
      evidence on comparative outcomes of robotic vs. conventional mitral surgery is
      limited, and results of the present meta-analysis should be interpreted with
      caution due to differing patient characteristics. However, it has been
      demonstrated that robotic mitral valve surgery can be safely performed by expert
      surgeons for selected patients. A successful robotic program is dependent on a
      specially trained team and a sufficient volume of referrals to attain and
      maintain safety.

PMID- 26309840
TI  - Evolution of the concept and practice of mitral valve repair.
AB  - The first successful mitral valve repair was performed by Elliot Cutler at
      Brigham and Women's Hospital in 1923. Subsequent evolution in the surgical
      techniques as well as multi-disciplinary cooperation between cardiac surgeons,
      cardiologists and cardiac anesthesiologists has resulted in excellent outcomes.
      In spite of this, the etiology of mitral valve pathology ultimately determines
      the outcome of mitral valve repair. 

PMID- 26309842
TI  - Current state of transcatheter mitral valve repair with the MitraClip.
AB  - BACKGROUND: Many patients affected with mitral valve regurgitation suffer from
      multiple comorbidities. The MitraClip device provides a safe means of
      transcatheter valve repair in patients with suitable mitral valve anatomy who are
      at prohibitive risk for surgery. We describe our early procedural outcomes and
      present a summary of the current state of MitraClip technology in the United
      States. METHODS: We performed a retrospective chart review of initial high-risk
      or inoperable patients who underwent MitraClip placement at our institution after
      completion of the EVEREST II study. We examined the primary outcome of 30-day
      mortality, and secondary outcomes included extent of reduction of mitral
      regurgitation (MR), New York Heart Association (NYHA) functional class
      improvement, length of stay, and major complications. RESULTS: A total of 115
      high-risk patients (mean Society of Thoracic Surgeons predicted risk of mortality
      9.4%+/-6.1%) underwent the MitraClip procedure at our institution between March
      2009 and April 2014. Co-morbidities including coronary artery disease (67.8%),
      pulmonary disease (39.1%) and previous cardiac surgery (44.3%) were common. The
      device was placed successfully in all patients with a 30-day mortality of 2.6%.
      All patients demonstrated 3+ or 4+ MR on preoperative imaging, and 80.7% of
      patients had trace or 1+ MR at hospital discharge. NYHA class improved
      substantially, with 79% of patients exhibiting class III or IV symptoms pre
      procedure and 81% reporting class I or II symptoms at one month follow-up.
      CONCLUSIONS: The MitraClip procedure provides a safe alternative to surgical or
      medical management for high-risk patients with MR and suitable valve anatomy. A
      comprehensive heart team approach is essential, with surgeons providing critical
      assessment of patient suitability for surgery versus percutaneous therapy as well
      as performance of the valve procedure.

PMID- 26309841
TI  - Mitral valve repair over five decades.
AB  - It has become evident that mitral valve (MV) repair is the preferable treatment
      for the majority of patients presenting with severe mitral regurgitation (MR).
      This success clearly testifies that the surgical procedure is accessible,
      reproducible and is carrying excellent long-lasting results. From the pre
      extracorporeal circulation's era to the last percutaneous approaches, a large
      variety of techniques have been proposed to address the different features of MV
      diseases. This article aimed at reviewing chronologically the development of
      these dedicated techniques through their origins and the debates that they
      generated in the literature. 

PMID- 26309843
TI  - Quantitation of mitral regurgitation after percutaneous MitraClip repair:
      comparison of Doppler echocardiography and cardiac magnetic resonance imaging.
AB  - OBJECTIVE: Percutaneous valve intervention for severe mitral regurgitation (MR)
      using the MitraClip is a novel technology. Quantitative assessment of residual MR
      by transthoracic echocardiography (TTE) is challenging, with multiple eccentric
      jets and artifact from the clips. Cardiovascular magnetic resonance (CMR) is the
      reference standard for left and right ventricular volumetric assessment. CMR
      phase-contrast flow imaging has superior reproducibility for quantitation of MR
      compared to echocardiography. The objective of this study was to establish the
      feasibility and reproducibility of CMR in quantitating residual MR after
      MitraClip insertion in a prospective study. METHODS: Twenty-five patients
      underwent successful MitraClip insertion. Nine were excluded due to non-magnetic
      resonance imaging (MRI) compatible implants or arrhythmia, leaving 16 who
      underwent a comprehensive CMR examination at 1.5 T (Siemens Aera) with
      multiplanar steady state free precession (SSFP) cine imaging (cine CMR), and
      phase-contrast flow acquisitions (flow CMR) at the mitral annulus atrial to the
      MitraClip, and the proximal aorta. Same-day echocardiography was performed with
      two-dimensional (2D) visualization and Doppler. CMR and echocardiographic data
      were independently and blindly analyzed by expert readers. Inter-rater comparison
      was made by concordance correlation coefficient (CCC) with 95% confidence
      intervals (CIs), and Bland-Altman (BA) methods. RESULTS: Mean age was 79 years,
      and mean LVEF was 44%+/-11% by CMR and 54%+/-16% by echocardiography. Inter
      observer reproducibility of echocardiographic visual categorical grading by
      expert readers was poor, with a CCC of 0.475 (-0.7, 0.74). Echocardiographic
      Doppler regurgitant fraction reproducibility was modest (CCC 0.59, 0.15-0.84; BA
      mean difference -3.7%, -38% to 31%). CMR regurgitant fraction reproducibility was
      excellent (CCC 0.95, 0.86-0.98; BA mean difference -2.4%, -11.9 to 7.0), with a
      lower mean difference and narrower limits of agreement compared to
      echocardiography. Categorical severity grading by CMR using published ranges had
      good inter-observer agreement (CCC 0.86, 0.62-0.95). CONCLUSIONS: CMR performs
      very well in the quantitation of MR after MitraClip insertion, with excellent
      reproducibility compared to echocardiographic methods. CMR is a useful technique
      for the comprehensive evaluation of residual regurgitation in patients after
      MitraClip. Technical limitations exist for both techniques, and quantitation
      remains a challenge in some patients.

PMID- 26309844
TI  - Progressive design concepts in off-pump left ventricular remodeling mitral valve
      repair devices.

PMID- 26309845
TI  - Myxomatous leaflet biological aberrations and potential therapeutic targets.

PMID- 26309846
TI  - How has robotic repair changed the landscape of mitral valve surgery?
AB  - The introduction of robotic technology has revolutionized the performance of
      certain cardiac surgical procedures such as mitral valve (MV) repair. The
      foundation of modern MV repair was laid by Dr. Dwight C. McGoon in 1958. The
      operation was first performed with robotic assistance by Carpentier in 1998 using
      rudimentary motion-assisted equipment. Today, four generations later,
      telemanipulation technology enables surgeons to carry out all known methods of MV
      repair traditionally performed by conventional sternotomy; utilizing tiny port
      access incisions to safely and reliably eliminate mitral regurgitation.
      Extubation in the operating room following robotic MV repair is now routine and
      its benefits are well-documented, including transfer to the step-down from the
      intensive care unit several hours after surgery. This, in turn, translates into
      diminished usage of blood products, decreased need for pain medication, earlier
      dismissal from hospital, more rapid return to work and improved patient
      satisfaction. In addition, smaller, more cosmetically appealing scars and
      comparable short and mid-term outcomes of robotic and open MV repair have made
      the robotic approach a preferred option for many patients who meet appropriate
      safety criteria. As these procedures become more commonplace in large structural
      heart practices, it is important to reflect upon how the robotic approach has
      changed the landscape of MV surgery. We discuss the evolution and current status
      of robotic MV repair founded upon the principles of safe and effective open
      mitral valvuloplasty techniques. We will explore the potential of the robotic
      platform to improve both early referral and patient acceptance of interventions
      to eliminate severe degenerative mitral regurgitation. 

PMID- 26309847
TI  - Designing innovative retractors and devices to facilitate mitral valve repair
      surgery.
AB  - Various devices have been developed to facilitate mitral valve surgery, including
      those that improve mitral valve exposure and assist surgeons with associated
      procedures. Choosing appropriate supporting devices when performing minimally
      invasive mitral valve surgery (MIMVS) through a minithoracotomy with endoscopic
      assistance is critical. Depending on the surgeon's preference, trans-thoracic or
      trans-working-port left atrial retractors can be utilized. Although the trans
      thoracic retractors provide a simple and orderly working space around the
      minithoracotomy working port, the positioning of the shaft is difficult and there
      is an implicit risk of chest wall bleeding. On the other hand, the trans-working
      port type provides excellent exposure, is easily handled and manipulated, and
      facilitates surgeries involving various anatomical structures without special
      training. A great deal of understanding and knowledge about retractors is
      necessary to achieve the optimal exposure required to facilitate surgical
      techniques, and to maintain a reproducible and safe surgical system during mitral
      valve surgery. 

PMID- 26309848
TI  - The butterfly technique.
AB  - Butterfly resection is a mitral valve repair technique for prolapsing posterior
      leaflets. The aim of butterfly resection is to optimize the geometry of the
      resultant new leaflet, with controlled height reduction for a prolapsing segment,
      without annular reduction. We have reported the concept of its design, its
      advantages in preventing post-repair systolic anterior motion (SAM), and
      excellent early and medium-term results. The present illustrated article
      describes the technical details of how we design and perform the butterfly
      technique. 

PMID- 26309849
TI  - Contemporary application of the edge-to-edge repair.

PMID- 26309850
TI  - The new butterfly technique-a sophisticated repair method for posterior leaflet
      prolapse.

PMID- 26309851
TI  - Sub-valvular repair of ischemic mitral regurgitation in a patient with severe
      tethering of mitral leaflets.

PMID- 26309852
TI  - Haircut mitral valve repair: posterior leaflet-plasty.

PMID- 26309853
TI  - "Papillary heads optimization" for more geometric repair of functional mitral
      regurgitation toward ventricular treatment.

PMID- 26309854
TI  - Asymptomatic mitral regurgitation-wait or operate?

PMID- 26309855
TI  - Tissue and mechanical heart valves.

PMID- 26309856
TI  - beta-III-Tubulin: a reliable marker for retinal ganglion cell labeling in
      experimental models of glaucoma.
AB  - AIM: To evaluate the reliability of beta-III-Tubulin protein as a retinal
      ganglion cell (RGC) marker in the experimental glaucoma model. METHODS: Glaucoma
      mouse models were established by injecting polystyrene microbeads into the
      anterior chamber of C57BL/6J mice, then their retinas were obtained 14d and 28d
      after the intraocular pressure (IOP) was elevated. Retinal flat mounts and
      sections were double-labeled by fluorogold (FG) and beta-III-Tubulin antibody or
      single-labeled by beta-III-Tubulin antibody, then RGCs were counted and compared
      respectively. RESULTS: IOP of the injected eyes were elevated significantly and
      reached the peak at 22.8+/-0.7 mm Hg by day 14 after injection, then dropped to
      11.3+/-0.7 mm Hg by day 28. RGC numbers counted by FG labeling and beta-III
      Tubulin antibody labeling were 64 807+/-4930 and 64614+/-5054 respectively in the
      control group, with no significant difference. By day 14, RGCs in the
      experimental group decreased significantly compared to the control group, but
      there was no significant difference between the FG labeling counting and the beta
      III-Tubulin antibody labeling counting either in the experimental group or in the
      control group. The result was similar by day 28, with further RGC loss.
      CONCLUSION: Our result suggested that the beta-III-Tubulin protein was not
      affected by IOP elevation and can be used as a reliable marker for RGC in
      experimental models of glaucoma.

PMID- 26309857
TI  - Pharmacokinetics and distributions of bevacizumab by intravitreal injection of
      bevacizumab-PLGA microspheres in rabbits.
AB  - AIM: To investigate the pharmacokinetics and distributions of bevacizumab by
      intravitreal injection of prepared bevacizumab-poly (L-lactic-co-glycolic acid)
      (PLGA) microspheres in rabbits, to provide evidence for clinical application of
      this kind of bevacizumab sustained release dosage form. METHODS: Bevacizumab was
      encapsulated into PLGA microsphere via the solid-in-oil-in-hydrophilic oil
      (S/O/hO) method. Fifteen healthy New Zealand albino-rabbits were used in
      experiments. The eyes of each rabbit received an intravitreal injection. The left
      eyes were injected with prepared bevacizumab-PLGA microspheres and the right eyes
      were injected with bevacizumab solution. After intravitreal injection, rabbits
      were randomly selected at days 3, 7, 14, 28 and 42 respectively, three animals
      each day. Then we used immunofluorescence staining to observe the distribution
      and duration of bevacizumab in rabbit eye tissues, and used the sandwich ELISA to
      quantify the concentration of free bevacizumab from the rabbit aqueous humor and
      vitreous after intravitreal injection. RESULTS: The results show that the
      concentration of bevacizumab in vitreous and aqueous humor after administration
      of PLGA formulation was higher than that of bevacizumab solution. The T1/2 of
      intravitreal injection of bevacizumab-PLGA microspheres is 9.6d in vitreous and
      10.2d in aqueous humor, and the T1/2 of intravitreal injection of soluble
      bevacizumab is 3.91d in vitreous and 4.1d in aqueous humor. There were
      statistical significant difference for comparison the results of the bevacizumab
      in vitreous and aqueous humor between the left and right eyes (P<0.05). The AUC0
      t of the sustained release dosage form was 1-fold higher than that of the soluble
      form. The relative bioavailability was raised significantly. The
      immunofluorescence staining of PLGA-encapsulated bevacizumab (b-PLGA) in rabbit
      eye tissues was still observed up to 42d. It was longer than that of the soluble
      form. CONCLUSION: The result of this study shows the beneficial effects of PLGA
      in prolonging the residency of bevacizumab in the vitreous. And the drug delivery
      system may have potential as a treatment modality for related disease.

PMID- 26309858
TI  - Rapamycin ameliorates experimental autoimmune uveoretinitis by inhibiting
      Th1/Th2/Th17 cells and upregulating CD4+CD25+ Foxp3 regulatory T cells.
AB  - AIM: To determine the effects of rapamycin on experimental autoimmune
      uveoretinitis (EAU) and investigate of role of rapamycin on T cell subsets in the
      disease. METHODS: EAU was induced in rats using peptides 1169 to 1191 of the
      interphotoreceptor binding protein (IRBP). Rapamycin (0.2 mg/kg/d) was
      administrated by intraperitoneal injection for a consecutive 7d after
      immunization. Th1/Th2/Th17 cytokines, TGF-beta1, and IL-6 produced by
      lymphocyteswere measured by ELISA, while Th17 cells and CD4+CD25+ regulatory T
      cells (Tregs) from rat spleen were detected by flow cytometry. RESULTS:
      Intraperitoneal treatment immediately after immunization dramatically ameliorated
      the clinical course of EAU. Clinical responses were associated with reduced
      retinal inflammatory cell infiltration and tissue destruction. Rapamycin induced
      suppression of Th1/Th2/Th17 cytokines, including IFN-gamma, IL-2, IL-17, IL-4,
      and IL-10 release from T lymphocytes of EAU rats, in vitro. Rapamycin also
      significantly increased TGF-beta1 production but had no effect on IL-6
      productionof T lymphocytes from EAU rats in vitro. Furthermore, rapamycin
      decreased the ratio of Th17 cells/CD4+T cells and upregulated Tregs in EAU, as
      detected by flow cytometry. CONCLUSION: Rapamycin effectively interferes with T
      cell mediated autoimmune uveitis by inhibiting antigen-specific T cell functions
      and enhancing Tregs in EAU. Rapamycin is a promising new alternative as an
      adjunct corticosteroid-sparing agent for treating uveitis.

PMID- 26309859
TI  - Phenotype of Usher syndrome type II assosiated with compound missense mutations
      of c.721 C>T and c.1969 C>T in MYO7A in a Chinese Usher syndrome family.
AB  - AIM: To identify the pathogenic mutations in a Chinese pedigree affected with
      Usher syndrome type II (USH2). METHODS: The ophthalmic examinations and
      audiometric tests were performed to ascertain the phenotype of the family. To
      detect the genetic defect, exons of 103 known RDs -associated genes including 12
      Usher syndrome (USH) genes of the proband were captured and sequencing analysis
      was performed to exclude known genetic defects and find potential pathogenic
      mutations. Subsequently, candidate mutations were validated in his pedigree and
      100 normal controls using polymerase chain reaction (PCR) and Sanger sequencing.
      RESULTS: The patient in the family occurred hearing loss (HL) and retinitis
      pigmentosa (RP) without vestibular dysfunction, which were consistent with
      standards of classification for USH2. He carried the compound heterozygous
      mutations, c.721 C>T and c.1969 C>T, in the MYO7A gene and the unaffected members
      carried only one of the two mutations. The mutations were not present in the 100
      normal controls. CONCLUSION: We suggested that the compound heterozygous
      mutations of the MYO7A could lead to USH2, which had revealed distinguished
      clinical phenotypes associated with MYO7A and expanded the spectrum of clinical
      phenotypes of the MYO7A mutations.

PMID- 26309860
TI  - Complement factors C1q, C3 and C5b-9 in the posterior sclera of guinea pigs with
      negative lens-defocused myopia.
AB  - AIM: To investigate the expression of complement factors in the posterior scleral
      fibroblasts of guinea pigs with negative lens-defocused myopia. METHODS: Eighteen
      guinea pigs were assigned randomly to two groups: the negative lens-defocused
      group (NLD group, n=9) and the normal control without treatment group (NC group,
      n=9). The effect of myopic induction was compared in three subgroups: eyes
      treated with a -10.00 D negative lens in the NLD group (NL group), eyes treated
      with a plano (0 D) lens in the NLD group (PL group), and untreated right eyes in
      the NC group (NC group). The following analyses were conducted at four weeks:
      examination of the refractive error via retinoscopy, assessment of complement C5b
      9 expression in the posterior scleral fibroblasts using immunohistochemistry, and
      measurements of complement C1q and C3 protein levels in the posterior sclera by
      Western blot. RESULTS: After an induction period of four weeks, a significant
      myopic shift was detected in the eyes of the NL group, relative to that of the PL
      and NC groups (P<0.05). Data analysis showed a significant increase in the
      percentage of C5b-9 immunopositive fibroblasts in the posterior sclera of the NL
      group eyes, compared to the PL group (q=11.50, P<0.001). Significantly higher
      levels of C1q (q=4.94, P=0.01) and C3 (q=4.07, P=0.03) protein were detected in
      the posterior sclera of NL group eyes, compared to the PL group. There were no
      significant difference between the PL and NC groups for C5b-9 (q=2.44, P=0.10),
      C1q (q=1.55, P=0.53) and C3 (q=0.98, P=0.77) in the posterior sclera. CONCLUSION:
      The data from present study provide evidence of the up-regulation of C5b-9, C1q
      and C3 in the posterior scleral fibroblasts in a NLD myopic animal model. The
      results suggest that the complement system may be involved in the development of
      myopia.

PMID- 26309861
TI  - Cirrhosis-induced morphological changes in the retina: possible role of
      endogenous opioid.
AB  - AIM: To investigate the impact of cirrhosis on retinal morphology and to evaluate
      the role of endogenous opioids as a mediator in cirrhosis induced retinal change.
      METHODS: Thirty-six male rats were divided into 3 main groups; the common bile
      duct ligated (BDL) group, the sham-operated (Sham) group and the unoperated
      (Unop) group. Then each of these three main groups was divided into two
      subgroups; the first subgroup received daily injection of naltrexone
      hydrochloride (NTX) and the second group was injected with normal saline (Saline)
      daily. After 28d, rats were anesthetized and their right eyes were enucleated and
      assessed for histological changes. The thickness of the rod and cons layer, outer
      nuclear layer, outer plexiform layer, inner nuclear layer, inner plexiform layer
      and ganglion cell layer for each eye were measured in micrometers by light
      microscope. RESULTS: Ganglion cell layer showed significant increase in thickness
      in the BDL group (P<0.05). This increase was eliminated in the group where BDL
      rats received daily intraperitoneal injection of naltrexone hydrochloride (20
      mg/kg). No other histological changes were detected in the other 5 layers we
      measured. CONCLUSION: The morphological change we detected in the retina of
      cirrhotic rats is probably due to opioids increased tone in cirrhosis since the
      increase in thickness in the ganglion cell layer was almost eliminated when
      naltrexone hydrochloride was injected. These results suggest a possible role for
      endogenous opioids in the morphological retinal changes detected in cirrhotic
      rats.

PMID- 26309862
TI  - Association of TCR-signaling pathway with the development of lacrimal gland
      benign lymphoepithelial lesions.
AB  - AIM: To identify the association of the T cell receptor (TCR) signaling with the
      development of benign lymphoepithelial lesions (BLEL) of the lacrimal gland.
      METHODS: We collected affected lacrimal gland tissues from 9 patients who
      underwent dacryoadenectomy in the Capital Medical University Beijing Tongren
      Hospital Eye Center between August 2010 and March 2013 and were confirmed to have
      lacrimal gland BLEL by histopathological analysis. Tumor tissues from 9 patients
      with orbital cavernous hemangioma were also collected and used as control. Whole
      genome gene expression microarray was used to compare gene expression profiles of
      affected lacrimal gland tissues from patients with lacrimal gland BLEL to those
      from of orbital cavernous hemangiomas. Differential expression of TCR pathway
      genes between these tissues was confirmed by polymerase chain reaction (PCR) and
      immunohistochemistry. RESULTS: Microarray analysis showed that in lacrimal glands
      with BLEL, 32 signaling pathways were enriched in the upregulated genes, while 25
      signaling pathways were enriched in the downregulated genes. In-depth analysis of
      the microarray data showed that the expression of 27 genes of the TCR signaling
      pathway increased significantly. To verify the differential expression of three
      of these genes, CD3, CD4, and interleukin (IL)-10, reverse transcription-PCR (RT
      PCR) and immunohistochemistry assays were performed. RT-PCR analysis showed that
      CD3 and CD4 were expressed in the lacrimal glands with BLEL, but IL-10 was not
      expressed. Immunohistochemistry confirmed that CD3 and CD4 proteins were also
      present, but IL-10 protein was not. CD3, CD4, or IL-10 expression was not found
      in the orbital cavernous hemangiomas with either RT-PCR or immunohistochemistry.
      CONCLUSION: TCR signaling pathway might be involved in the pathogenesis of
      lacrimal gland BLEL.

PMID- 26309864
TI  - Correction.
AB  - [This corrects the article DOI: 10.3980/j.issn.2222-3959.2015.02.08.]. 

PMID- 26309863
TI  - Dectin-1 agonist curdlan modulates innate immunity to Aspergillus fumigatus in
      human corneal epithelial cells.
AB  - AIM: To explore the immunomodulatory effects of curdlan on innate immune
      responses against Aspergillus fumigatus (A. fumigatus) in cultured human corneal
      epithelial cells (HCECs), and whether C-type lectin receptor Dectin-1 mediates
      the immunomodulatory effects of curdlan. METHODS: The HCECs were stimulated by
      curdlan in different concentrations (50, 100, 200, 400 ug/mL) for various time.
      Then HCECs pretreated with or without laminarin (Dectin-1 blocker, 0.3 mg/mL) and
      curdlan were stimulated by A. fumigatus hyphae. The mRNA and protein production
      of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were
      determined by real-time quantitative polymerase chain reaction and enzyme-linked
      immunosorbent assay, respectively. The protein level of Dectin-1 was measured by
      Western blot. RESULTS: Curdlan stimulated mRNA expression of TNF-alpha and IL-6
      in a dose and time dependent manner in HCECs. Curdlan pretreatment before A.
      fumigatus hyphae stimulation significantly enhanced the expression of TNF-alpha
      and IL-6 at mRNA and protein levels compared with A. fumigatus hyphae stimulation
      group (P<0.05). Both curdlan and A. fumigatus hyphae up-regulated Dectin-1
      protein expression in HCECs, and Dectin-1 expression was elevated to 1.5- to 2
      fold by curdlan pretreatment followed hyphae stimulation. The Dectin-1 blocker
      laminarin suppressed the mRNA expression and protein production of TNF-alpha and
      IL-6 induced by curdlan and hyphae (P<0.05). CONCLUSION: These findings
      demonstrated that curdlan pretreatment enhanced the inflammatory response induced
      by A. fumigatus hyphae in HCECs. Dectin-1 is essential for the immunomodulatory
      effects of curdlan. Curdlan may have high clinical application values in fungal
      keratitis treatment.

PMID- 26309865
TI  - Evaluating the safety of intracameral bevacizumab application using oxidative
      stress and apoptotic parameters in corneal tissue.
AB  - AIM: To investigate the possible effects of intracameral bevacizumab on oxidative
      stress parameters and apoptosis in corneal tissue. METHODS: In total, 30 rats
      were assigned randomly into the following three groups of 10 rats each: a sham
      group (Group 1; n=10), a control group [Group 2; balanced salt solution (BSS) was
      administered at 0.01 mL; n=10], and a treatment group (Group 3; bevacizumab was
      administered at 0.25 mg/0.01 mL; n=10). The total antioxidant status (TAS) and
      the total oxidant status (TOS) in the corneal tissue and blood samples were
      measured, and the oxidative stress index (OSI) was calculated. Additionally,
      corneal tissue histopathology was evaluated for caspase-3 and -8 staining and
      apoptotic activity. RESULTS: In the blood samples, the TAS, TOS, and OSI levels
      were not significantly different (all P>0.05). Compared with the sham and control
      groups, the TOS and OSI levels in the corneal tissues were significantly
      different in the bevacizumab group (all P<0.05). No statistically significant
      differences were observed between the sham and control groups (all P>0.05).
      However, compared with the sham and control groups, greater immunohistochemical
      staining for caspases-3 and -8 and an elevated level of apoptotic activity were
      observed in the bevacizumab group. CONCLUSION: This study revealed that
      intracameral bevacizumab injections seemed to be systemically safe but may have
      elicited local toxic effects in the corneal tissue, as indicated by the oxidative
      stress parameters and histopathological evaluations.

PMID- 26309866
TI  - Investigation of the efficiency of intrastromal ring segments with cross-linking
      using different sequence and timing for keratoconus.
AB  - AIM: To evaluate and compare the efficacy and stability of intrastromal corneal
      ring segment (ICRs) implantation with cross-linking (CXL) using different
      sequence and timing. METHODS: In this single retrospective study, 86 keratoconic
      eyes subjected the ICRs implantation. We analyzed only 41 eyes that had complete
      follow-ups. They were divided into three groups: ICRs implantation was applied
      only (group normal), ICRs first followed by CXL immediately (group CXL-S), CXL
      first followed by ICRs long after (group CXL-B). The visual acuity, refractive
      results, keratometry were compared preoperatively and 1y postoperatively. Their
      differences among the three groups were also analyzed. RESULTS: Group normal
      comprised 25 eyes, group CXL-S 8 eyes, and group CXL-B 8 eyes. There were
      improvements in the mean uncorrected distance visual acuity (UDVA) and the mean
      corrected distance visual acuity (CDVA) compared preoperatively and 1y
      postoperatively {UDVA: 0.31 (P=0.030) logarithmic minimum angle of resolution
      [logMAR] group normal, 0.4 (P=0.020) group CXL-S, 0.45 (P=0.001) group CXL-B;
      CDVA: 0.21 logMAR (P=0.013) group normal, 0.30 (P=0.036) group CXL-S; 0.26
      (P=0.000) group CXL-B}. The refractive and topographic outcomes also showed
      improvements. In terms of comparisons among the three groups, all the P values
      were above 0.05, showing no significant difference. But only group CXL-B had
      improvement in UDVA and CDVA for all the patients. CONCLUSION: With safety and
      good visual outcomes, ICRs implantation is a viable alternative for keratoconus.
      No significant difference was found among these three groups.

PMID- 26309867
TI  - Nd: Yag laser iridotomy in Shaffer-Etienne grade 1 and 2: angle widening in our
      case studies.
AB  - AIM: To obtain widening of a potentially occludable angle, in according to
      Kanski's indications, through preventive Nd:Yag laser iridotomy. The
      observational study was performed by using gonioscopy for the selection and
      follow-up of 1165 treated eyes and exploiting Shaffer-Etienne gonioscopic
      classification as a quality/quantity test of the angle recession. METHODS:
      Between September 2000 and July 2012, 586 patients were selected at the
      Outpatients' Ophthalmological Clinic of the Policlinico Umberto I of Rome in
      order to undergo Nd: Yag laser iridotomy. A Goldmann type contact lens, Q
      switched mode, 2-3 defocus, and 7-9 mJ intensity with 2-3 impulse discharges were
      used for surgery. RESULTS: From as early as the first week, a whole 360 degrees 
      angle widening were evident in the patients, thus showing the success of Nd:Yag
      laser iridotomy in solving relative pupil block. The angle remained narrow by 270
      degrees  in 14 eyes only, despite repetitions of further treatment with laser
      iridotomy in a different part of the iris, twice in 10 eyes and three times in 4
      eyes. CONCLUSION: Nd:Yag laser iridotomy revealed itself as being a safe and
      effective treatment in widening those critical Shaffer-Etienne grade 1 and 2
      potentially occludable angles.

PMID- 26309868
TI  - Autologous sclera-muscle flaps technique in evisceration with hydroxyapatite
      implantation.
AB  - AIM: To provide superior cosmetic results and reduce complications, unlike
      traditional evisceration coupled with implant insertion technique and its
      modifications, we have developed a novel and simple technique for anophthalmic
      patients. METHODS: All patients who underwent the scleral-muscle flaps procedure
      in evisceration with the placement of hydroxyapatite implant were included in the
      study. Main outcome measures were complications such as exposure, infection,
      chemosis, conjunctival inclusion cysts, granulomas. Meanwhile, implant motility
      was indirectly measured and the results were collected and analyzed. RESULTS: A
      total of twenty-eight patients were enrolled in the study. Eighteen were men
      (64.29%) and ten were women (35.71%). Ages ranged from 18 to 65y (mean age, 32
      years old). Mean follow-up was 12.32mo (range, 9-16mo). All patients received a
      hydroxyapatite implant. The average diameter of the implant was 19.29+/-1.36 mm
      (range, 18-22 mm). Minor complications occurred in 3 patients, and a major
      complication was observed in 1 patient. Mean motility were 11.04+/-1.45 mm
      horizontally (range, 7-14 mm) and 8.57+/-1.50 mm vertically (range, 5-12 mm).
      CONCLUSION: The sclera-muscle flaps technique in evisceration with hydroxyapatite
      implantation is simple and practical that eases the surgical procedure, enables a
      proper size hydroxyapatite implantation, distinctively reduces complications and
      provides superior surgery results, especially the motility of the implant.

PMID- 26309869
TI  - Correction of low corneal astigmatism in cataract surgery.
AB  - AIM: To evaluate and compare aspheric toric intraocular lens (IOL) implantation
      and aspheric monofocal IOL implantation with limbal relaxing incisions (LRI) to
      manage low corneal astigmatism (1.0-2.0 D) in cataract surgery. METHODS: A
      prospective randomized comparative clinical study was performed. There were
      randomly recruited 102 eyes (102 patients) with cataracts associated with corneal
      astigmatism and divided into two groups. The first group received toric IOL
      implantation and the second one monofocal IOL implantation with peripheral
      corneal relaxing incisions. Outcomes considered were: visual acuity,
      postoperative residual astigmatism, endothelial cell count, the need for
      spectacles, and patient satisfaction. To determine the postoperative toric axis,
      all patients who underwent the toric IOL implantation were further evaluated
      using an OPD Scan III (Nidek Co, Japan). Follow-up lasted 6mo. RESULTS: The mean
      uncorrected distance visual acuity (UCVA) and the best corrected visual acuity
      (BCVA) demonstrated statistically significant improvement after surgery in both
      groups. At the end of the follow-up the UCVA was statistically better in the
      patients with toric IOL implants compared to those patients who underwent
      implantation of monofocal IOL plus LRI. The mean residual refractive astigmatism
      was of 0.4 D for the toric IOL group and 1.1 D for the LRI group (P<0.01). No
      difference was observed in the postoperative endothelial cell count between the
      two groups. CONCLUSION: The two surgical procedures demonstrated a significant
      decrease in refractive astigmatism. Toric IOL implantation was more effective and
      predictable compared to the limbal relaxing incision.

PMID- 26309870
TI  - Comparison of posterior capsule opacification at 360-degree square edge
      hydrophilic and sharp edge hydrophobic acrylic intraocular lens in diabetic
      patients.
AB  - AIM: To compare posterior capsule opacification (PCO) degree and visual functions
      after phacoemulsification in eyes implanted with 360-degree square edge
      hydrophilic acrylic intraocular lens (IOL) (570C C-flex, Rayner) and sharp edge
      hydrophobic acrylic IOL (Sensar AR40e, AMO) in diabetic patients. METHODS: Sixty
      diabetic patients underwent uneventful phacoemulsification and randomly implanted
      one of the two IOLs. The PCO value was measured by retroillumination photographs
      and Evaluation of Posterior Capsule Opacification (EPCO) 2000 image-analysis
      software at 1, 6, 12, and 24mo after surgery. Visual acuity, and contrast
      sensitivity in photopic and mesopic conditions were also examined at each follow
      up time point. The incidence of eye that required Nd:YAG laser posterior
      capsulotomy were also compared. RESULTS: There was not any statistically
      significant difference in PCO scores between Rayner C-flex 570C group and Sensar
      AR40e group at each follow up time point. Visual acuity, Nd:YAG capsulotomy
      incidence and contrast sensitivity also had no significant difference during the
      24mo follow-up. CONCLUSION: For diabetic patients, Rayner 570C C-flex and Sensar
      AR40e IOLs are same effective for prevent PCO. The 360-degree square edge design
      maybe is a good alternative technique to improve PCO prevention.

PMID- 26309871
TI  - Optical performance of toric intraocular lenses in the presence of decentration.
AB  - AIM: To evaluate the optical performance of toric intraocular lenses (IOLs) after
      decentration and with different pupil diameters, but with the IOL astigmatic axis
      aligned. METHODS: Optical performances of toric T5 and SN60AT spherical IOLs
      after decentration were tested on a theoretical pseudophakic model eye based on
      the Hwey-Lan Liou schematic eye using the Zemax ray-tracing program. Changes in
      optical performance were analyzed in model eyes with 3-mm, 4-mm, and 5-mm pupil
      diameters and decentered from 0.25 mm to 0.75 mm with an interval of 5 degrees 
      at the meridian direction from 0 degrees  to 90 degrees . The ratio of the
      modulation transfer function (MTF) between a decentered and a centered IOL
      (MTFDecentration/MTFCentration) was calculated to analyze the decrease in optical
      performance. RESULTS: Optical performance of the toric IOL remained unchanged
      when IOLs were decentered in any meridian direction. The MTFs of the two IOLs
      decreased, whereas optical performance remained equivalent after decentration.
      The MTFDecentration/MTFCentration ratios of the IOLs at a decentration from 0.25
      mm to 0.75 mm were comparable in the toric and SN60AT IOLs. After decentration,
      MTF decreased further, with the MTF of the toric IOL being slightly lower than
      that of the SN60AT IOL. Imaging qualities of the two IOLs decreased when the
      pupil diameter and the degree of decentration increased, but the decrease was
      similar in the toric and spherical IOLs. CONCLUSIONS: Toric IOLs were comparable
      to spherical IOLs in terms of tolerance to decentration at the correct axial
      position.

PMID- 26309872
TI  - High order aberration and straylight evaluation after cataract surgery with
      implantation of an aspheric, aberration correcting monofocal intraocular lens.
AB  - AIM: To evaluate the quality of vision in respect to high order aberrations and
      straylight perception after implantation of an aspheric, aberration correcting,
      monofocal intraocular lens (IOL). METHODS: Twenty-one patients (34 eyes) aged 50
      to 83y underwent cataract surgery with implantation of an aspheric, aberration
      correcting IOL (Tecnis ZCB00, Abbott Medical Optics). Three months after surgery
      they were examined for uncorrected (UDVA) and corrected distance visual acuity
      (CDVA), contrast sensitivity (CS) under photopic and mesopic conditions with and
      without glare source, ocular high order aberrations (HOA, Zywave II) and retinal
      straylight (C-Quant). RESULTS: Postoperatively, patients achieved a postoperative
      CDVA of 0.0 logMAR or better in 97.1% of eyes. Mean values of high order
      abberations were +0.02+/-0.27 (primary coma components) and -0.04+/-0.16
      (spherical aberration term). Straylight values of the C-Quant were 1.35+/-0.44
      log which is within normal range of age matched phakic patients. The CS
      measurements under mesopic and photopic conditions in combination with and
      without glare did not show any statistical significance in the patient group
      observed (P>=0.28). CONCLUSION: The implantation of an aspherical aberration
      correcting monofocal IOL after cataract surgery resulted in very low residual
      higher order aberration (HOA) and normal straylight.

PMID- 26309873
TI  - Angle parameter changes of phacoemulsification and combined phacotrabeculectomy
      for acute primary angle closure.
AB  - AIM: To evaluate the difference in angle parameters and clinical outcome
      following phacoemulsification and combined phacotrabeculectomy in patients with
      acute primary angle closure (APAC) using ultrasound biomicroscopy (UBM). METHODS:
      Patients (n=23, 31 eyes) were randomized to receive phacoemulsification or
      combined phacotrabeculectomy (n=24, 31 eyes). Best-corrected visual acuity
      (BCVA), intraocular pressure (IOP), the main complications following surgery, and
      indentation gonioscopy and angle parameters measured using UBM were documented
      preoperatively and postoperatively. RESULTS: The improvement in BCVA in the
      phacoemulsification group was significantly greater than in the combined group
      (P<0.05). IOP in the phacoemulsification group was slightly higher than in the
      combined group following 1wk of follow-up (P<0.05), whereas there was no
      significant difference between the two groups at the latter follow-up (P>0.05).
      Phacoemulsification alone resulted in a slight increase in the trabecular ciliary
      processes distance compared with the combined surgery (P<0.05), whereas the other
      angle parameters showed no significant difference between the groups.
      Complications in combined group were greater than phacoemulsification only group.
      CONCLUSION: Both surgeries effectively opened the drainage angle and deepened the
      anterior chamber, and IOP was well controlled postoperatively. However,
      phacoemulsification showed better efficacy in improving visual function and
      showed reduced complications following surgery.

PMID- 26309874
TI  - Bleb needling outcomes for failed trabeculectomy blebs in Asian eyes: a 2-year
      follow up.
AB  - AIM: To describe the outcomes of bleb needling in primary glaucoma in an Asian
      tertiary eye centre over a 2y period. To compare the success rates between
      primary angle-closure glaucoma (PACG) and primary open angle glaucoma (POAG).
      Lastly, to identify factors associated with success of bleb needling. METHODS:
      This was a retrospective review of 227 patients who underwent bleb needling
      between June 2009 and June 2011 in Singapore National Eye Centre. The 5
      fluorouracil (5-FU) augmented bleb needling was performed either at the slit lamp
      or in the operating theatre. Repeat bleb needlings were performed as necessary.
      Complete success was defined as maintenance of intraocular pressure (IOP) >=6 mm
      Hg and <=21 mm Hg, in the absence of further surgery or use of antiglaucoma
      medication. Qualified success met the above criteria with or without use of
      antiglaucoma medications. RESULTS: One hundred and seventy-five eyes completed
      the two-year follow up. Sixty-nine percent of participants had POAG and 31% had
      PACG. The mean interval between filtering surgery and bleb needling was 299.9+/
      616.4d for POAG and 167.1+/-272.2d for PACG. Mean needling attempts were 1.9+/
      1.4 and 2+/-1.6 for POAG and PACG respectively. In general, there was a
      statistically significant reduction of IOP ranging from 21.9% to 26.8% from month
      1 through to month 24. The complete success rates at month 6 were 70.0% for POAG
      and 65.7% for PACG. At month 12, this decreased to 62.2% for POAG and PACG and at
      month 24, 57.9% for POAG and 63.0% for PACG respectively. The qualified success
      rates at month 6 for POAG and PACG were 23.8% and 29.9% respectively, 32.2% and
      29.2% at month 12, and 34.7% and 29.6% at month 24. The success rates between
      POAG and PACG were not significantly different (P>0.05 for complete and qualified
      success at months 6, 12 and 24). An increased number of needlings and higher pre
      needling IOP were associated with failure. CONCLUSION: The 5-FU augmented bleb
      needling within one year of trabeculectomy in Asian eyes can provide clinically
      significant IOP lowering of more than 20% for 2y. POAG and PACG had similar
      complete success rates (58% and 63% respectively). Factors associated with
      greater risk of procedure failure included increased number of needlings and
      higher pre-needling IOP. Asian eyes have a greater propensity for scarring but
      bleb needling, if performed in a timely manner can rescue bleb function.

PMID- 26309875
TI  - Ultrasound biomicroscopy in patients with unilateral pseudoexfoliation.
AB  - AIM: To compare the anterior segment morphology evaluated using ultrasound
      biomicroscopy (UBM) in patients with clinical pseudoexfoliation syndrome (XFS) in
      one eye and no clinical XFS in the fellow eye. METHODS: Thirty patients with
      unilateral XFS were included in the study. All patients underwent evaluation of
      their anterior segment using UBM with and without dilatation with 1%
      cyclopentolate. The anterior chamber depth (ACD), lens thickness (LT), anterior
      chamber angle (ACA), ciliary body thickness (CBT), scleral thickness (ST),
      trabeculae -ciliary processes distance (T-CPD), and iris-ciliary processes
      distance (I-CPD) were measured using UBM scans. All results between the eyes with
      clinical XFS and their fellow eyes without clinical XFS were then compared.
      RESULTS: Before dilatation the eyes with XFS (4.350+/-0.531 mm) were found to
      have a significantly thicker lens (P=0.002) than the eyes without XFS (4.238+/
      0.540 mm). In addition after dilatation, the eyes with XFS (4.310+/-0.500 mm)
      were found to have a significantly thicker lens than the eyes without XFS
      (4.160+/-0.480 mm) (P=0.019). The average ACD, for the group with XFS, comparing
      pre-dilatation (2.616+/-0.349 mm) and post-dilatation measurements (2.714+/
      0.413) was found to be statistically increased (P=0.014). The average ACD,
      comparing pre-dilatation to post-dilatation measurements in patients without XFS
      (2.680+/-0.360), (2.720+/-0.500) was found to be statistically unchanged
      (P=0.450). DISCUSSION: Crystalline lenses tended to be thicker in the eyes with
      clinical pseudoexfoliation than their fellow eyes without pseudoexfoliation.

PMID- 26309876
TI  - Clinical characteristics of intermediate uveitis in adult Turkish patients.
AB  - AIM: To describe the clinical characteristics of Turkish patients with
      intermediate uveitis (IU) and to investigate the effect of clinical findings and
      complications on final visual acuity (VA). METHODS: We retrospectively analyzed
      the medical records of patients with IU who had at least 6mo of follow-up and
      were older than 16y. RESULTS: A total of 78 eyes of 45 patients were included in
      the study and the mean follow-up period was 19.4mo. The mean age at the time of
      presentation was 42.9s. Systemic disease associations were found in 17.7% of
      cases; sarcoidosis (8.8%) and multiple sclerosis (6.6%) were the most common
      diseases. Recurrence rate (odds ratio=45.53; 95%CI: 2.181-950.58), vitritis
      equals to or more than 3+ cells (odds ratio=57.456; 95%CI: 4.154-794.79) and
      presenting with VA less than 20/40 (odds ratio=43.81; 95%CI: 2.184-878.71) were
      also found as high risk factors for poor final VA. At the last follow-up
      examination, 67.9% of eyes had VA of 20/40 or better. CONCLUSION: IU is
      frequently seen at the beginning of the fourth decade of life. The disease is
      most commonly idiopathic in adult Turkish patients. Patients with severe vitritis
      at presentation and patients with frequent recurrences are at high risk for poor
      visual outcome.

PMID- 26309877
TI  - Visual function and vision-related quality of life after vitrectomy for
      idiopathic macular hole: a 12mo follow-up study.
AB  - AIM: To investigate the visual function and the relationship with vision-related
      quality of life (VRQOL) after macular hole repair surgery. METHODS: Prospective
      case series. Thirty-six consecutive eyes in 36 patients who underwent pars plana
      vitrectomy (PPV) and internal limiting membrane (ILM) peeling were included. The
      25-item National Eye Institute Visual Function Questionnaire (VFQ-25) was
      answered by the participants before and 3 and 12mo after operation. Follow-up
      visits examinations included best-corrected visual acuity (BCVA), clinical
      examination, and central macular thickness (CMT) measured by optical coherence
      tomography (OCT). RESULTS: Macular-hole closure was achieved in 35 of 36 eyes
      (97.2%). At baseline and months 3 and 12, the logMAR BCVAs (mean+/-SD) were
      1.15+/-0.47, 0.68+/-0.53 (P<0.0001 versus baseline), and 0.55+/-0.49 (P<0.001
      versus baseline, P =0.273 versus month 3), respectively; the CMTs (um) were 330+/
      81, 244+/-62 (P<0.001 versus baseline), and 225+/-58 (P<0.001 versus baseline,
      P=0.222 versus month 3), respectively; the median preoperative VFQ-25 composite
      score of 73.50 (63.92-81.13) increased postoperatively to 85.50 (80.04-89.63) at
      3mo (P<0.001) and 86.73(82.50-89.63) at 12mo (P<0.001) respectively. The improved
      BCVA was correlated with improvements in five subscales (r=-0.605 to -0.336,
      P<0.001 to P=0.046) at 12mo. CONCLUSION: PPV with ILM peeling improved anatomic
      outcome, visual function, and VRQOL. The improved BCVA was an important factor
      related to the improved VRQOL.

PMID- 26309878
TI  - Characterisation of human non-proliferative diabetic retinopathy using the
      fractal analysis.
AB  - AIM: To investigate and quantify changes in the branching patterns of the retina
      vascular network in diabetes using the fractal analysis method. METHODS: This was
      a clinic-based prospective study of 172 participants managed at the
      Ophthalmological Clinic of Cluj-Napoca, Romania, between January 2012 and
      December 2013. A set of 172 segmented and skeletonized human retinal images,
      corresponding to both normal (24 images) and pathological (148 images) states of
      the retina were examined. An automatic unsupervised method for retinal vessel
      segmentation was applied before fractal analysis. The fractal analyses of the
      retinal digital images were performed using the fractal analysis software ImageJ.
      Statistical analyses were performed for these groups using Microsoft Office Excel
      2003 and GraphPad InStat software. RESULTS: It was found that subtle changes in
      the vascular network geometry of the human retina are influenced by diabetic
      retinopathy (DR) and can be estimated using the fractal geometry. The average of
      fractal dimensions D for the normal images (segmented and skeletonized versions)
      is slightly lower than the corresponding values of mild non-proliferative DR
      (NPDR) images (segmented and skeletonized versions). The average of fractal
      dimensions D for the normal images (segmented and skeletonized versions) is
      higher than the corresponding values of moderate NPDR images (segmented and
      skeletonized versions). The lowest values were found for the corresponding values
      of severe NPDR images (segmented and skeletonized versions). CONCLUSION: The
      fractal analysis of fundus photographs may be used for a more complete
      undeTrstanding of the early and basic pathophysiological mechanisms of diabetes.
      The architecture of the retinal microvasculature in diabetes can be quantitative
      quantified by means of the fractal dimension. Microvascular abnormalities on
      retinal imaging may elucidate early mechanistic pathways for microvascular
      complications and distinguish patients with DR from healthy individuals.

PMID- 26309879
TI  - Effect of suction on macular thickness and retinal nerve fiber layer thickness
      during LASIK used femtosecond laser and Moria M2 microkeratome.
AB  - AIM: To compare the effect of suction on the macular thickness and retinal nerve
      fiber layer (RNFL) thickness during laser in situ keratomileusis (LASIK) used
      Ziemer FEMTO LDV femtosecond laser (Ziemer group) and Moria M2 automated
      microkeratome (Moria group) for flap creation. METHODS: Fourier-domain optical
      coherence tomography (FD-OCT) was used to measure macular thickness, ganglion
      cell complex thickness and (RNFL) thickness of 204 eyes of 102 patients with the
      Ziemer femtosecond laser (102 eyes) and the Moria M2 microkeratome (102 eyes)
      before surgery and 30min; 1, 3d; 1wk; 1, 3mo; 1y after surgery. RESULTS: The
      average foveal thickness and parafoveal retinal thickness 30min after the surgery
      were statistically more than that before surgery (Ziemer P<0.001, P=0.003 and
      Moria P=0.001, P=0.006) and the effect was less in the Ziemer group than that in
      the Moria group (P all<0.05). The ganglion cell complex thickness was not
      significantly changed in both groups (P all>0.05). The RNFL thickness was
      statistically less 30min after surgery in both groups (P=0.014, P<0.001), but the
      influence was less in Ziemer group than that in Moria group (P=0.038). However,
      the RNFL thickness had recovered to the preoperative level only 1d after surgery.
      CONCLUSION: The suction of femtosecond laser and mechanical microkeratome led to
      the increase in macular central fovea thickness and the decrease in RNFL
      thickness values at the early stage after LASIK. The effect of suction on macular
      and the RNFL thicknesses in Ziemer group is smaller than that in Moria group.

PMID- 26309880
TI  - Comparison of the femtosecond laser and mechanical microkeratome for flap cutting
      in LASIK.
AB  - AIM: To compare refractive results, higher-order aberrations (HOAs), contrast
      sensitivity and dry eye after laser in situ keratomileusis (LASIK) performed with
      a femtosecond laser versus a mechanical microkeratome for myopia and astigmatism.
      METHODS: In this prospective, non-randomized study, 120 eyes with myopia received
      a LASIK surgery with the VisuMax femtosecond laser for flap cutting, and 120 eyes
      received a conventional LASIK surgery with a mechanical microkeratome. Flap
      thickness, visual acuity, manifest refraction, contrast sensitivity function
      (CSF) curves, HOAs and dry-eye were measured at 1wk; 1, 3, 6mo after surgery.
      RESULTS: At 6mo postoperatively, the mean central flap thickness in femtosecond
      laser procedure was 113.05+/-5.89 um (attempted thickness 110 um), and 148.36+/
      21.24 um (attempted thickness 140 um) in mechanical microkeratome procedure. An
      uncorrected distance visual acuity (UDVA) of 4.9 or better was obtained in more
      than 98% of eyes treated by both methods, a gain in logMAR lines of corrected
      distance visual acuity (CDVA) occurred in more than 70% of eyes treated by both
      methods, and no eye lost >=1 lines of CDVA in both groups. The difference of the
      mean UDVA and CDVA between two groups at any time post-surgery were not
      statistically significant (P>0.05). The postoperative changes of spherical
      equivalent occurred markedly during the first month in both groups. The total
      root mean square values of HOAs and spherical aberrations in the femtosecond
      treated eyes were markedly less than those in the microkeratome treated eyes
      during 6mo visit after surgery (P<0.01). The CSF values of the femtosecond
      treated eyes were also higher than those of the microkeratome treated eyes at all
      space frequency (P<0.01). The mean ocular surface disease index scores in both
      groups were increased at 1wk, and recovered to preoperative level at 1mo after
      surgery. The mean tear breakup time (TBUT) of the femtosecond treated eyes were
      markedly longer than those of the microkeratome treated eyes at postoperative 1,
      3mo (P<0.01). CONCLUSION: Both the femtosecond laser and the mechanical
      microkeratome for LASIK flap cutting are safe and effective to correct myopia,
      with no statistically significant difference in the UDVA, CDVA during 6mo follow
      up. Refractive results remained stable after 1mo post-operation for both groups.
      The femtosecond laser may have advantages over the microkeratome in the flap
      thickness predictability, fewer induced HOAs, better CSF, and longer TBUT.

PMID- 26309881
TI  - Comparison of the extrusion rate of Crawford tubes.
AB  - AIM: To compare the outcomes of dacryocystorhinostomy (DCR) using traditional
      Crawford tubes (TCT) and Crawford tubes with suture (CTS) in the lumen. METHODS:
      Retrospective case series consisting of patients who underwent DCR between 2008
      and 2013. RESULTS: A total of 61 DCRs were performed on 50 patients. Patients who
      underwent DCR using CTS had higher rates of prolapse compared to the TCT group
      (50% vs 9.4%; P=0.003). Stent removal occurred earlier in patients who received
      CTS (3.3mo vs 5.1mo; P=0.004). Success rates were equivalent between the two
      groups (75% vs 81.1%; P=0.684). CONCLUSION: CTS in the lumen increases the risk
      of prolapse, prompting earlier tube removal in patients following DCR for
      nasolacrimal duct obstruction (NLDO). Earlier removal of tubes does not appear to
      significantly decrease success rates.

PMID- 26309882
TI  - Visual findings as primary manifestations in patients with intracranial tumors.
AB  - AIM: To evaluate the visual findings as primary manifestations in patients with
      intracranial tumors. METHODS: The medical charts of the patients with
      intracranial tumors who initially admitted to the Neuro-ophthalmology and
      Strabismus Department with ocular complaints between August 1999 and December
      2012 were reviewed retrospectively. The detailed clinical history and the
      findings of neuro-ophthalmologic examination were recorded. Ocular symptoms and
      signs, the types and locations of intracranial tumors, and the duration of
      symptoms before the diagnosis were evaluated. RESULTS: The mean age of 11 women
      (61.1%) and 7 men (38.9%) was 42.2+/-11.0 (range 20-66y) at the time of
      intracranial tumor diagnosis. Initial symptoms were transient visual
      obscurations, visual loss or visual field defect in 16 cases (88.9%), and
      diplopia in 2 cases (11.1%). Neuro-ophthalmologic examination revealed normal
      optic discs in both eyes of 6 patients (33.3%), paleness, atrophy or edema of
      optic disc in 12 patients (66.7%), and sixth cranial nerve palsy in 2 patients
      (11.1%). Visual acuity ranged between normal vision and loss of light perception.
      Cranial imaging demonstrated craniopharyngioma (n=1), plasmacytoma (n=1),
      meningioma (n=6; olfactory groove and tuberculum sellae, pontocerebellar angle,
      anterior cranial fossa, frontal vertex, suprasellar region), and pituitary
      macroadenoma (n=10). The mean duration between the onset of visual disturbances
      and the diagnosis of intracranial tumor was 9.8+/-18mo (range 3d-6y). CONCLUSION:
      The ophthalmologist is frequently the first physician to encounter a patient with
      clinical manifestations of intracranial tumors that may cause neurological and
      ocular complications. Neuro-ophthalmologic findings should be carefully evaluated
      to avoid a delay in the diagnosis of intracranial tumors.

PMID- 26309883
TI  - Association between metabolic syndrome and age-related cataract.
AB  - AIM: To determine the effect of metabolic syndrome on age-related cataract
      formation. METHODS: We analyzed data for 2852 subjects [41.8% men and 58.2%
      women; mean (+/-SD) age, 52.9+/-13.9y], taken from the Korea National Health and
      Nutrition Examination Survey 2008. Metabolic syndrome was diagnosed by criteria
      proposed by the Joint Interim Societies. Cataract was diagnosed by using the Lens
      Opacities Classification System III. The association between metabolic syndrome
      and cataract was determined using age-adjusted and multivariable logistic
      regression analyses. RESULTS: In multivariable analyses, men with metabolic
      syndrome had a 64% increased risk of nuclear cataract [odds ratio (OR), 1.64; 95%
      confidence interval (CI), 1.12-2.39]. Women with metabolic syndrome had a 56%
      increased risk of cortical cataract (OR, 1.56; 95% CI, 1.06-2.30). Men and women
      with metabolic syndrome had a 46% (OR, 1.46; 95% CI, 1.01-2.12) and 49% (OR,
      1.49; 95% CI, 1.07-2.08) increased risk of any cataract, respectively. The
      prevalence of nuclear and any cataract significantly increased with an increasing
      number of disturbed metabolic components in men, and prevalence of all types of
      cataracts increased in women. Men using hypoglycemic medication had an increased
      risk of nuclear (OR, 2.62; 95% CI, 1.41-4.86) and any (OR, 2.27; 95% CI, 1.14
      4.51) cataract, and women using antidyslipidemia medication had an increased risk
      of cortical (OR, 2.18; 95% CI, 1.12-4.24) and any (OR, 2.21; 95% CI, 1.14-4.26)
      cataract. CONCLUSION: Metabolic syndrome and its components, such as abdominal
      obesity, high blood pressure, and impaired fasting glucose, are associated with
      age-related cataract formation in the Korean population.

PMID- 26309884
TI  - Ocular biometry in the adult population in rural central China: a population
      based, cross-sectional study.
AB  - AIM: To describe the distribution and determinants of ocular biometric parameters
      and to ascertain the relative importance of these determinants in a large
      population of adults in rural central China. METHODS: A population-based, cross
      sectional study performed in rural central China included 1721 participants aged
      40 or more years. Ocular biometrical parameters including axial length (AL),
      anterior chamber depth (ACD), radius of corneal curvature (K) and horizontal
      corneal diameter [white-to-white (WTW) distance] were measured using non-contact
      partial coherence interferometry [intraocular lens (IOL)-Master]. RESULTS: Ocular
      biometric data on 1721 participants with a average age of 57.0+/-8.7y were
      analyzed at last. The general mean AL, ACD, mean corneal curvature radius (MCR),
      WTW were 22.80+/-1.12, 2.96+/-0.36, 7.56+/-0.26 and 11.75+/-0.40 mm,
      respectively. The mean values of each parameter in 40 to 49, 50 to 59, 60 to 69,
      and 70 to 91 years age groups were as follows: AL, 22.77+/-0.87, 22.76+/-1.06,
      22.89+/-1.41, 22.92+/-0.80 mm; ACD, 3.10+/-0.32, 2.98+/-0.34, 2.86+/-0.36, 2.77+/
      0.35 mm; MCR, 7.58+/-0.25, 7.54+/-0.26, 7.55+/-0.26, 7.49+/-0.28 mm; WTW, 11.79+/
      0.38, 11.75+/-0.40, 11.72+/-0.41, 11.67+/-0.41 mm. The AL, ACD, MCR and WTW were
      correlated with age and the AL was correlated with height and weight. CONCLUSION:
      Our findings can serve as an important normative reference for multiple purposes
      and may help to improve the quality of rural eye care.

PMID- 26309885
TI  - Research on induced pluripotent stem cells and the application in ocular tissues.
AB  - Induced pluripotent stem cells (iPSCs) were firstly induced from mouse
      fibroblasts since 2006, and then the research on iPSCs had made great progress in
      the following years. iPSCs were established from different somatic cells through
      DNA, RNA, protein or small molecule pathways and transduction vehicles. With
      continuous improvement of technology on reprogramming, the induction of iPSCs
      became more secure and effective, and showed enormous promise for clinical
      applications. We reviewed different reprogramming of somatic cells, four kinds of
      pathways of reprogramming and three types of transduction vehicles, and discuss
      the research of iPSCs in ophthalmology and the prospect of iPSCs applications. 

PMID- 26309887
TI  - Posterior segment nucleotomy for dislocated sclerotic cataractous lens using
      chandelier endoilluminator and sharp tipped chopper.
AB  - AIM: To describe a new surgical technique for managing dislocated sclerotic
      cataractous lens. METHODS: Six patients with advanced posteriorly dislocated
      cataracts were operated at a tertiary care centre and analyzed retrospectively.
      After standard 3 port 23 G pars plana vitrectomy and perfluorocarbon liquid
      (PFCL) injection, the dislocated white cataract was held with occlusion using
      phaco fragmatome and then chopped into smaller pieces with a sharp tipped chopper
      using 25 G chandelier endoilluminator. Each piece was emulsified individually.
      Following aspiration of PFCL, Fluid Air Exchange was done in all the cases and
      surgery completed uneventfully. RESULTS: Best corrected visual acuity (BCVA) in
      all the patients was better than 6/12 after one month of follow up. No serious
      complications were noted till minimum 6mo of follow up. CONCLUSION: Four port
      posterior segment nucleotomy with a chandelier endoilluminator, fragmatome and a
      chopper appears to be a safe, easy and effective procedure for managing
      dislocated sclerotic cataractous nuclei. Ultrasonic energy used and adverse
      thermal effects of the fragmatome on the sclera may be lesser.

PMID- 26309888
TI  - Results of intravitreal dexamethasone implant 0.7 mg (Ozurdex(r)) in non
      infectious posterior uveitis.
AB  - AIM: To evaluate the safety and efficacy of dexamethasone implant in patients
      with non-infectious posterior uveitis with cystoid macular edema (CME). METHODS:
      Retrospective analysis of patients reports with CME secondary to non-infectious
      uveitis treated with dexamethasone implant. Data included type of posterior
      uveitis, any systemic immunosuppressive therapy, Early Treatment Diabetic
      Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA), central macular
      thickness (CMT) on optical coherence tomography (OCT) and signs of intraocular
      inflammation at baseline and then at 2wk postoperatively and monthly thereafter.
      Follow-up is up to 10mo. Any per-operative and post-operative complications were
      recorded. RESULTS: Six eyes of 4 patients with CME due to non-infectious
      posterior uveitis treated with dexamethasone implant. Diagnosis included
      idiopathic panuveitis, birdshot chorioretinopathy and idiopathic intermediate
      uveitis. At baseline mean ETDRS BCVA was 63 letters and mean CMT 556 um at 2wk
      postoperatively mean ETDRS BCVA improved to 70 letters and mean CMT decreased to
      329 um. All eyes showed clinical evidence of decreased inflammation. The duration
      of effect of the implant was 5 to 6mo and retreatment was required in 2 eyes. Two
      patients required antiglaucoma therapy for increased intraocular pressures.
      CONCLUSION: In patients with non-infectious posterior uveitis dexamethasone
      implant can be a short-term effective treatment option for controlling
      intraocular inflammation.

PMID- 26309886
TI  - Potential role of nuclear receptor ligand all-trans retinoic acids in the
      treatment of fungal keratitis.
AB  - Fungal keratitis (FK) is a worldwide visual impairment disease. This infectious
      fungus initiates the primary innate immune response and, later the adaptive
      immune response. The inflammatory process is related to a variety of immune
      cells, including macrophages, helper T cells, neutrophils, dendritic cells, and
      Treg cells, and is associated with proinflammatory, chemotactic and regulatory
      cytokines. All-trans retinoic acids (ATRA) have diverse immunomodulatory actions
      in a number of inflammatory and autoimmune conditions. These retinoids regulate
      the transcriptional levels of target genes through the activation of nuclear
      receptors. Retinoic acid receptor alpha (RAR alpha), retinoic acid receptor gamma
      (RAR gamma), and retinoid X receptor alpha (RXR alpha) are expressed in the
      cornea and immune cells. This paper summarizes new findings regarding ATRA in
      immune and inflammatory diseases and analyzes the perspective application of ATRA
      in FK. 

PMID- 26309889
TI  - Adjustable muscle plication: a new surgical technique for strabismic patients
      with high risk for anterior segment ischemia.

PMID- 26309890
TI  - Visco chop- a new technique for nucleus separation for soft cataracts in
      femtolaser assisted cataract surgery.

PMID- 26309891
TI  - Tachyphylaxis during ranibizumab treatment of exudative age-related macular
      degeneration.

PMID- 26309892
TI  - Subfoveal choroidal thickness changes after intravitreal bevacizumab therapy for
      neovascular age-related macular degeneration.

PMID- 26309893
TI  - Comment on bilateral same-session intravitreal injections.

PMID- 26309894
TI  - Inhaled Nitric Oxide as an Adjunctive Treatment for Cerebral Malaria in Children:
      A Phase II Randomized Open-Label Clinical Trial.
AB  - Background.  Children with cerebral malaria (CM) have high rates of mortality and
      neurologic sequelae. Nitric oxide (NO) metabolite levels in plasma and urine are
      reduced in CM. Methods.  This randomized trial assessed the efficacy of inhaled
      NO versus nitrogen (N2) as an adjunctive treatment for CM patients receiving
      intravenous artesunate. We hypothesized that patients treated with NO would have
      a greater increase of the malaria biomarker, plasma angiopoietin-1 (Ang-1) after
      48 hours of treatment. Results.  Ninety-two children with CM were randomized to
      receive either inhaled 80 part per million NO or N2 for 48 or more hours. Plasma
      Ang-1 levels increased in both treatment groups, but there was no difference
      between the groups at 48 hours (P = not significant [NS]). Plasma Ang-2 and
      cytokine levels (tumor necrosis factor-alpha, interferon-gamma, interleukin [IL]
      1beta, IL-6, IL-10, and monocyte chemoattractant protein-1) decreased between
      inclusion and 48 hours in both treatment groups, but there was no difference
      between the groups (P = NS). Nitric oxide metabolite levels-blood methemoglobin
      and plasma nitrate-increased in patients treated with NO (both P < .05). Seven
      patients in the N2 group and 4 patients in the NO group died. Five patients in
      the N2 group and 6 in the NO group had neurological sequelae at hospital
      discharge. Conclusions.  Breathing NO as an adjunctive treatment for CM for a
      minimum of 48 hours was safe, increased blood methemoglobin and plasma nitrate
      levels, but did not result in a greater increase of plasma Ang-1 levels at 48
      hours. 

PMID- 26309895
TI  - Adenocarcinoma of the urinary bladder.
AB  - Adenocarcinoma is an uncommon malignancy in the urinary bladder which may arise
      primarily in the bladder as well as secondarily from a number of other organs.
      Our aim is to provide updated information on primary and secondary bladder
      adenocarcinomas, with focus on pathologic features, differential diagnosis, and
      clinical relevance. Primary bladder adenocarcinoma exhibits several different
      growth patterns, including enteric, mucinous, signet-ring cell, not otherwise
      specified, and mixed patterns. Urachal adenocarcinoma demonstrates similar
      histologic features but it can be distinguished from bladder adenocarcinoma on
      careful pathologic examination. Secondary bladder adenocarcinomas may arise from
      the colorectum, prostate, endometrium, cervix and other sites.
      Immunohistochemical study is valuable in identifying the origin of secondary
      adenocarcinomas. Noninvasive neoplastic glandular lesions, adenocarcinoma in situ
      and villous adenoma, are frequently associated with bladder adenocarcinoma. It is
      also important to differentiate bladder adenocarcinoma from a number of
      nonneoplastic lesions in the bladder. Primary bladder adenocarcinoma has a poor
      prognosis largely because it is usually diagnosed at an advanced stage. Urachal
      adenocarcinoma shares similar histologic features with bladder adenocarcinoma,
      but it has a more favorable prognosis than bladder adenocarcinoma, partly due to
      the relative young age of patients with urachal adenocarcinoma. 

PMID- 26309896
TI  - Drug resistance in castration resistant prostate cancer: resistance mechanisms
      and emerging treatment strategies.
AB  - Several mechanisms facilitate the progression of hormone-sensitive prostate
      cancer to castration-resistant prostate cancer (CRPC). At present, the approved
      chemotherapies for CRPC include systemic drugs (docetaxel and cabazitaxel) and
      agents that target androgen signaling, including enzalutamide and abiraterone.
      While up to 30% of patients have primary resistance to these treatments, each of
      these drugs confers a significant survival benefit for many. Over time, however,
      all patients inevitably develop resistance to treatment and their disease will
      continue to progress. Several key mechanisms have been identified that give rise
      to drug resistance. Expression of constitutively active variants of the androgen
      receptor, such as AR-V7, intracrine androgens and overexpression of androgen
      synthesis enzymes like AKR1C3, and increased drug efflux through ABCB1 are just
      some of the many discovered mechanisms of drug resistance. Treatment strategies
      are being developed to target these pathways and reintroduce drug sensitivity.
      Niclosamide has been discovered to reduce AR-V7 activity and synergized to
      enzalutamide. Indomethacin has been explored to inhibit AKR1C3 activity and
      showed to be able to reverse resistance to enzalutamide. ABCB1 transport activity
      can be mitigated by the phytochemical apigenin and by antiandrogens such as
      bicalutamide, with each improving cellular response to chemotherapeutics. By
      better understanding the mechanisms by which drug resistance develops improved
      treatment strategies will be made possible. Herein, we review the existing
      knowledge of CRPC therapies and resistance mechanisms as well as methods that
      have been identified which may improve drug sensitivity. 

PMID- 26309897
TI  - Therapeutic challenges in renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) is a malignancy that in advanced disease, is highly
      resistant to systemic therapies. Elucidation of the angiogenesis pathways and
      their intrinsic signaling interactions with the genetic and metabolic
      disturbances within renal cell carcinoma variants has ushered in the era of
      "targeted therapies". Advanced surgical interventions and novel drugs targeting
      VEGF and mTOR, have improved patient survival and prolonged clinically stable
      disease states. This review discusses the current understanding of diagnostic
      challenges and the mechanism-based clinical evidence on therapeutic management of
      advanced RCC. 

PMID- 26309898
TI  - Signaling mechanisms coupled to CXCL12/CXCR4-mediated cellular proliferation are
      PTEN-dependent.
AB  - A key difference between normal and malignant prostate cells in vitro and in vivo
      is that both alleles of PTEN are largely intact in normal benign prostate glands
      and cultured epithelial cells, whereas one or both alleles of PTEN are mutant or
      deleted in the majority of prostate tumors and malignant prostate cancer cell
      lines. Intact PTEN suppresses phosphorylation of Akt downstream of PI3K
      activation in non-transformed cells whereas Akt phosphorylation is unimpeded in
      malignant cells that are often PTEN-deficient. We have previously shown that
      activation of the CXCL12/CXCR4 axis transactivates the EGFR to promote pro
      proliferative signaling preferentially through the Raf/MEK/Erk pathway in benign
      prostate epithelial cells. These cells demonstrate little basal pAkt and these
      levels do not increase with CXCL12 stimulation because PTEN is intact and fully
      functional. Thus, inactivation of PTEN may be the critical factor that modulates
      downstream signaling and the specific CXCL12-stimulated proliferative responses
      of non-transformed and transformed prostate epithelial cells. Based on these
      data, we hypothesize that the CXCL12/CXCR4-mediated activation of downstream pro
      proliferative signaling through the Raf/MEK/Erk or PI3K/Akt pathways is modulated
      by PTEN status. 

PMID- 26309899
TI  - Mean platelet volume and varicocele: comparison between adolescents and adults.
AB  - PURPOSE: To evaluate the association between varicocele and MPV values in
      pediatric and adult patients. And its association with different clinical
      parameters. MATERIALS AND METHODS: We retrospectively analyzed the medical charts
      of patients treated for varicocele at our Institution between December 2010 and
      December 2014. The study patients were divided into three groups: group 1-
      patients with varicocele without testicular hypotrophy treated for scrotal
      discomfort or infertility (percutaneous varicocelecomy-scheloembolization); group
      2- (control group) patients without varicocele; group 3- patients with varicocele
      and testicular hypotrophy (laparoscopic varicocelectomy). The study compared the
      grade of varicocele and MPV before surgery; age-related MPV and MPV cumulative
      value between the groups. RESULTS: After revision of the study 145 medical charts
      (group 1: 47 patients, group 2: 52 patients, group 3: 46 patients), and in
      compliance with the inclusion and exclusion criteria established, 127 patients
      were considered for the study; we evaluated 42 patients in group 1, 46 patients
      in group 2 and 39 patients in group 3. Patients with varicocele had higher MPV
      value than controls but only in adulthood. Testicular hypotrophy associated with
      varicocele is not a confusing factor. CONCLUSIONS: Even if MPV is higher in
      adults with varicocele as reported by other studies, but this result is not thrue
      in adolescents and its is not correlated with testicular hypotrophy; some
      confunding factors, i.e. andrological disease or smoking status, could be the
      reasons of different results present on medical literature.

PMID- 26309900
TI  - Unilateral hypoplastic kidney and ureter associated with diverse mesonephric
      remnant hyperplasia.
AB  - Mesonephric remnants have been rarely reported in the genitourinary system and
      sometimes impose a diagnostic challenge both clinically and pathologically. We
      reported a case of mesonephric remnant hyperplasia with mixed acinar/tubular and
      epididymis/vas deferens-like morphologies occurring in the renal parenchyma of a
      unilateral hypoplastic kidney, which has not been previously described. 

PMID- 26309901
TI  - NMDA receptor antibodies: A rare association in inflammatory demyelinating
      diseases.
AB  - OBJECTIVES: To analyze the frequency of NMDA receptor (NMDAR) antibodies in
      patients with various inflammatory demyelinating diseases of the CNS and to
      determine their clinical correlates. METHODS: Retrospective case-control study
      from 2005 to 2014 with the detection of serum IgG antibodies to NMDAR, aquaporin
      4, and myelin oligodendrocyte glycoprotein by recombinant live cell-based
      immunofluorescence assays. Fifty-one patients with acute disseminated
      encephalomyelitis, 41 with neuromyelitis optica spectrum disorders, 34 with
      clinically isolated syndrome, and 89 with multiple sclerosis (MS) were included.
      Due to a known association of NMDAR antibodies with seizures and behavioral
      symptoms, patients with those clinical manifestations were preferentially
      included and are therefore overrepresented in our cohort. Nine patients with
      NMDAR encephalitis, 94 patients with other neurologic diseases, and 48 healthy
      individuals were used as controls. RESULTS: NMDAR antibodies were found in all 9
      patients with NMDAR encephalitis but in only 1 of 215 (0.5%) patients with
      inflammatory demyelination and in none of the controls. This patient had
      relapsing-remitting MS with NMDAR antibodies present at disease onset, with an
      increase in NMDAR antibody titer with the onset of psychiatric symptoms and
      cognitive deficits. CONCLUSION: In demyelinating disorders, NMDAR antibodies are
      uncommon, even in those with symptoms seen in NMDAR encephalitis.

PMID- 26309902
TI  - Improvement of GAD65-associated autoimmune epilepsy with testosterone replacement
      therapy.

PMID- 26309903
TI  - New type of encephalomyelitis responsive to trimethoprim/sulfamethoxazole
      treatment in Japan.
AB  - OBJECTIVE: To determine the causative pathogen and investigate the effective
      treatment of a new type of encephalomyelitis with an unknown pathogen in Japan
      and report the preliminary ultrastructural and genomic characterization of the
      causative agent. METHODS: From 2005 to 2012, we treated 4 Japanese patients with
      geographic clustering and comparable clinical features, serum/CSF cytology, and
      radiologic findings. Brain biopsy was conducted in all patients to analyze
      neuropathologic changes by histology, and electron microscopy was applied to
      reveal the features of the putative pathogen. Genomic DNA was obtained from the
      affected brain tissues and CSF, and an unbiased high-throughput sequencing
      approach was used to screen for specific genomic sequences indicative of the
      pathogen origin. RESULTS: All patients exhibited progressive dementia with
      involuntary tongue movements. Cytologic examination of CSF revealed elevated
      mononuclear cells. Abnormal MRI signals were observed in temporal lobes,
      subcortical white matter, and spinal cord. Biopsied brain tissue exhibited
      aggregated periodic acid-Schiff-positive macrophages and 2-7 MUm diameter
      round/oval bodies without nuclei or cell walls scattered around the vessels.
      Unbiased high-throughput sequencing identified more than 100 archaea-specific DNA
      fragments. All patients were responsive to trimethoprim/sulfamethoxazole (TMP
      SMX) plus corticosteroid therapy. CONCLUSIONS: We report 4 cases of
      encephalomyelitis due to an unknown pathogen. On the basis of ultrastructural and
      genomic studies, we propose a new disease entity resulting from a causative
      pathogen having archaeal features. TMP-SMX therapy was effective against this new
      type of encephalomyelitis.

PMID- 26309904
TI  - Optimizing the Exercise Prescription for Depression: The Search for Biomarkers of
      Response.
AB  - There is growing support for the efficacy of exercise interventions for the
      treatment of individuals who present with mild-to-moderate depression. The
      variability in treatment response across studies and individuals suggests that
      the efficacy of exercise for depression will be most optimal when prescribed to
      individuals who are most prone to respond. The present article reviews
      contemporary theoretical accounts and recent empirical data pointing to
      neuroinflammatory states and neurotrophin production as possible biomarkers of
      the antidepressant response to exercise. The larger exercise and depression
      literatures provide justification for elevated levels of pro-inflammatory
      cytokines and deficits in BDNF production as putative matching variables.
      Although there is some empirical support for these hypotheses, it is clear that
      this research warrants replication and extension. We offer a few suggestions for
      future research in this emerging area.

PMID- 26309906
TI  - Educational inequalities in aging-related declines in fluid cognition and the
      onset of cognitive pathology.
AB  - BACKGROUND: Education has been robustly associated with cognitive reserve and
      dementia, but not with the rate of cognitive aging, resulting in some confusion
      about the mechanisms of cognitive aging. This study uses longitudinal data to
      differentiate between trajectories indicative of healthy versus pathological
      cognitive aging. METHODS: Participants included 9,401 Health and Retirement Study
      respondents aged 55 and older who completed cognitive testing regularly over 17.3
      years until most recently in 2012. Individual-specific random change-point
      modeling was used to identify age of incident pathological decline; acceleration
      is interpreted as indicating likely onset of pathological decline when it is
      significant and negative. RESULTS: These methods detect incident dementia
      diagnoses with specificity/sensitivity of 89.3%/44.3%, 5.6 years prior to
      diagnosis. Each year of education was associated with 0.09 (95% CI, 0.087-0.096;
      P<0.001) standard deviation higher baseline cognition and delayed onset of
      cognitive pathology (HR, 0.98; 95% CI, 0.96-0.99; P=0.006). CONCLUSION:
      Longitudinal random change-point modeling was able to reliably identify incident
      dementia. Accounting for incident cognitive pathology, we find that education
      predicts cognitive capability and delayed onset pathological declines.

PMID- 26309907
TI  - Folate-Dependent Hydrolysis of Acetyl-Coenzyme A by Recombinant Human and Rodent
      Arylamine N-Acetyltransferases.
AB  - Arylamine N-acetyltransferases (NATs) are drug and xenobiotic metabolizing
      enzymes that catalyze the N-acetylation of arylamines and hydrazines and the O
      acetylation of N-hydroxy-arylamines. Recently, studies report that human NAT1 and
      mouse Nat2 hydrolyze acetyl-coenzyme A (AcCoA) into acetate and coenzyme A in a
      folate-dependent fashion, a previously unknown function. In this study, our goal
      was to confirm these findings and determine the apparent Michaelis-Menten kinetic
      constants (Vmax and Km) of the folate-dependent AcCoA hydrolysis for human
      NAT1/NAT2, and the rodent analogs rat Nat1/Nat2, mouse Nat1/Nat2, and hamster
      Nat1/Nat2. We also compared apparent Vmax values for AcCoA hydrolysis and N
      acetylation of the substrate para-aminobenzoic acid (PABA). Human NAT1 and its
      rodent analogs rat Nat2, mouse Nat2 and hamster Nat2 catalyzed AcCoA hydrolysis
      in a folate-dependent manner. Rates of AcCoA hydrolysis were between 0.25 - 1% of
      the rates for N-acetylation of PABA catalyzed by human NAT1 and its rodent
      orthologs. In contrast to human NAT1, human NAT2 and its rodent analogs rat Nat1,
      mouse Nat1, and hamster Nat1 did not hydrolyze AcCoA in a folate-dependent
      manner. These results are consistent with the possibility that human NAT1 and its
      rodent analogs regulate endogenous AcCoA levels.

PMID- 26309908
TI  - The Newborn Screening Quality Assurance Program at the Centers for Disease
      Control and Prevention: Thirty-five Year Experience Assuring Newborn Screening
      Laboratory Quality.
AB  - Newborn screening is the largest genetic testing effort in the United States and
      is considered one of the ten great public health achievements during the first 10
      years of the 21st century. For over 35 years, the Newborn Screening Quality
      Assurance Program (NSQAP) at the US Centers for Disease Control and Prevention
      has helped NBS laboratories ensure that their testing does not delay diagnosis,
      minimizes false-positive reports, and sustains high-quality testing performance.
      It is a multi-component program that provides comprehensive quality assurance
      services for dried blood spot testing. The NSQAP, the Biochemical Mass
      Spectrometry Laboratory (BMSL), the Molecular Quality Improvement Program (MQIP)
      and the Newborn Screening Translation Research Initiative (NSTRI), aid screening
      laboratories achieve technical proficiency and maintain confidence in their
      performance while processing large volumes of specimens daily. The accuracy of
      screening tests could be the difference between life and death for many babies;
      in other instances, identifying newborns with a disorder means that they can be
      treated and thus avoid life-long disability or severe cognitive impairment.
      Thousands of newborns and their families have benefited from reliable and
      accurate testing that has been accomplished by a network of screening
      laboratories and the NSQAP, BMSL, MQIP and NSTRI.

PMID- 26309909
TI  - Accurate assessment of liver steatosis in animal models using a high throughput
      Raman fiber optic probe.
AB  - Due to the shortage of healthy donor organs, steatotic livers are commonly used
      for transplantation, placing patients at higher risk for graft dysfunction and
      lower survival rates. Raman Spectroscopy is a technique which has shown the
      ability to rapidly detect the vibration state of C-H bonds in triglycerides. The
      aim of this study is to determine whether conventional Raman spectroscopy can
      reliably detect and quantify fat in an animal model of liver steatosis. Mice and
      rats fed a methionine and choline-deficient (MCD) and control diets were
      sacrificed on one, two, three and four weeks' time points. A confocal Raman
      microscope, a commercial Raman (iRaman) fiber optic probe and a highly sensitive
      Raman fiber optic probe system, the latter utilizing a 785 nm excitation laser,
      were used to detect changes in the Raman spectra of steatotic mouse livers. Thin
      layer chromatography was used to assess the triglyceride content of liver
      specimens, and sections were scored blindly for fat content using histological
      examination. Principal component analysis (PCA) of Raman spectra was used to
      extract the principal components responsible for spectroscopic differences with
      MCD week (time on MCD diet). Confocal Raman microscopy revealed the presence of
      saturated fats in mice liver sections. A commercially available handheld Raman
      spectroscopy probe could not distinguish the presence of fat in the liver whereas
      our specially designed, high throughput Raman system could clearly distinguish
      lobe-specific changes in fat content. In the left lobe in particular, the Raman
      PC scores exhibited a significant correlation (R(2) = 0.96) with the gold
      standard, blinded scoring by histological examination. The specially designed,
      high throughput Raman system can be used for clinical purposes. Its application
      to the field of transplantation would enable surgeons to determine the hepatic
      fat content of the donor's liver in the field prior to proceeding with organ
      retrieval. Next steps include validating these results in a prospective analysis
      of human liver transplantation implant biopsies. 

PMID- 26309905
TI  - One health, multiple challenges: The inter-species transmission of influenza A
      virus.
AB  - Influenza A viruses are amongst the most challenging viruses that threaten both
      human and animal health. Influenza A viruses are unique in many ways. Firstly,
      they are unique in the diversity of host species that they infect. This includes
      waterfowl (the original reservoir), terrestrial and aquatic poultry, swine,
      humans, horses, dog, cats, whales, seals and several other mammalian species.
      Secondly, they are unique in their capacity to evolve and adapt, following
      crossing the species barrier, in order to replicate and spread to other
      individuals within the new species. Finally, they are unique in the frequency of
      inter-species transmission events that occur. Indeed, the consequences of novel
      influenza virus strain in an immunologically naive population can be devastating.
      The problems that influenza A viruses present for human and animal health are
      numerous. For example, influenza A viruses in humans represent a major economic
      and disease burden, whilst the poultry industry has suffered colossal damage due
      to repeated outbreaks of highly pathogenic avian influenza viruses. This review
      aims to provide a comprehensive overview of influenza A viruses by shedding light
      on interspecies virus transmission and summarising the current knowledge
      regarding how influenza viruses can adapt to a new host.

PMID- 26309910
TI  - An electrochemical DNA sensor based on polyaniline/graphene: high sensitivity to
      DNA sequences in a wide range.
AB  - A label-free electrochemical DNA sensor was fabricated by deposition of
      polyaniline and pristine graphene nanosheet (P/G(ratios)) composites in different
      mass ratios, DNA probe and bovine serum albumin (BSA) layer by layer on the
      surface of a glassy carbon electrode (GCE). Electrochemical impedance
      spectroscopy (EIS) was employed to monitor every step of fabrication of
      P/G(ratio)-based DNA sensors and to evaluate the detection results in terms of
      the hybridization of complementary DNA, mutant DNA and non-complementary DNA. The
      results illustrate that the P/G(ratio)-based DNA sensor could highly efficiently
      detect complementary DNA from 0.01 pm to 1 MUm and discriminate single-nucleotide
      polymorphisms (SNPs). In the process of detection, double-stranded DNA (dsDNA),
      resulting from hybridization of a DNA probe, escaping from or remaining on the
      sensor surface, was monitored by changing the ratio of polyaniline (PANI) to
      graphene, which was decided by the competition between the electrostatic
      interaction and Brownian motion.

PMID- 26309911
TI  - Optical microscopy imaging for the diagnosis of the pharmacological reaction of
      mouse embryonic stem cell-derived cardiomyocytes (mESC-CMs).
AB  - Quantitative diagnosis of pharmacological chronotropic reactions on mouse
      embryonic stem cell-derived cardiomyocytes (mESC-CMs) was successfully performed
      by utilizing derivative imaging analysis of videos recorded with a microscope
      camera at 30 Hz frame rate and 680 * 510 pixel resolution. The imaging analysis
      algorithm, developed in our lab, generated the contractile profile of the cells
      which was exploited for drug effect profiling. Six drugs such as isoproterenol
      (0.01-1 MUM), quinidine (2-200 MUM), propranolol (0.03-30 MUM), verapamil (0.01-1
      MUM), sotalol (1-100 MUM), and acetylsalicylic acid (0.1-10 MUM) were
      administered and the quantitative medication effect was determined. Among the
      negative chronotropic agents administered, verapamil was found to be the most
      potent while sotalol was found to be the least potent at the micromolar level.
      Simultaneous measurement of the field potential and contractile motion in the
      verapamil effect test showed a coherent result. Moreover, this approach can
      provide insights into the contraction-relaxation conditions which are not
      available in the common electrophysiological approach. With these findings, it is
      expected that this study can aid in providing a simple and reliable in vitro mESC
      CM-based screening platform for cardiovascular effect profiling of candidate
      drugs. 

PMID- 26309912
TI  - The future of business.

PMID- 26309913
TI  - Patient compliance with photoprotection.

PMID- 26309914
TI  - Prolonged QT: A rare cause of cardiac arrest.
AB  - A prolonged QT interval can be caused by medications,electrolyte abnormalities,
      or long QT syndrome, a genetic mutation that prolongs the action potential.
      Torsades de pointes is a potentially fatal polymorphic VT most often associated
      with prolonged QT interval. This article focuses on recognizing and treating drug
      induced torsades de pointes.

PMID- 26309915
TI  - AORTITIS SYNDROME WITH SPECIAL REFERENCE TO ITS CLINICAL PICTURE AND ETIOLOGY.

PMID- 26309916
TI  - THE PRE-THERAPEUTIC CLASSIFICATION OF CO-MORBIDITY IN CHRONIC DISEASE.
AB  - In a patient with a particular index disease, the term co-morbidity refers to any
      additional co-existing ailment. The failure to classify and analyze co-morbid
      diseases has led to many difficulties in medical statistics. The omissions create
      misleading data in mortality rates for a general population, and in fatality
      rates for an individual disease. In particular, neglect of co-morbidity may cause
      spurious comparisons during the planning and evaluation of treatment for patients
      with apparently identical diagnoses. Co-morbidity can alter the clinical course
      of patients with the same diagnosis by affecting the time of detection,
      prognostic anticipations, therapeutic selection, and post-therapeutic outcome of
      the index disease. In addition to these direct effects on clinical course, co
      morbidity plays a role in intellectual decisions that may alter the statistical
      categories of diagnostic classification. These decisions deal with the
      attribution of symptoms in 'polypathic' patients and with the selection of an
      inception manifestation for the index disease. In order to maintain consistency
      in the management of research data, certain principles of co-morbid differential
      diagnosis can be developed according to anatomic relation, pathogenetic
      interplay, and chronometric features of the diseases under consideration.

PMID- 26309917
TI  - DISTINGUISHING PHYSIOLOGIC VARIATION FROM ANALYTIC VARIATION.

PMID- 26309918
TI  - ESSENTIAL TRACE METALS IN MAN: MOLYBDENUM.
AB  - A survey of human exposures to molybdenum, a trace metal essential for almost all
      forms of life, was made by analyzing human tissues of 381 subjects from around
      the world by emission spectroscopy, and foods and beverages by a colorimetric
      method. Molybdenum was present in all human livers, kidneys and adrenals
      examined. Total body content of United States subjects was less than 9 mg and
      most organs and tissues contained little. Unlike other essential trace metals,
      mean concentrations of molybdenum in liver and kidney were relatively low in the
      newborn, rising to a peak in the second decade of life and declining slightly
      thereafter. Mean hepatic and renal concentrations of United States and foreign
      subjects were similar, but the latter had more molybdenum and it occurred more
      frequently in other organs and tissues. Only a few correlations of molybdenum
      with other trace metals in tissues were significant. The daily intake of
      molybdenum in standard diets was about 350 MUg. Fish and animal meats supplied
      variable amounts; legumes, whole grains and their products supplied the majority.
      Plant foods high in purines were usually high in molybdenum, whereas most
      vegetables had little or none. Molybdenum in wheat was depleted in refining to
      white flour; that in sugar was concentrated in molasses and syrups. Rats fed a
      diet low in molybdenum had higher serum uric acid levels than those given added
      molybdenum. There is evidence that dental caries may be prevented by a high
      intake of molybdenum. It is possible that renal xanthine calculi may result from
      low intakes and that molybdenum may somehow be involved in disturbances of uric
      acid metabolism.

PMID- 26309919
TI  - HYPERLIPIDEMIA IN AN ADULT DIABETIC POPULATION.
AB  - Of 98 adult-onset diabetic patients selected at random from an ambulatory clinic,
      37.8 per cent were found to have hyperlipidemia. In follow-up examination of the
      hyperlipidemic patients, 23 per cent had hyper-beta-lipoproteinemia (Type II), 58
      per cent had hyper-pre-beta-lipoproteinemia (Type IV), 13 per cent had increased
      plasma beta-and pre-beta-lipoproteins (combined type) and 6 per cent had reverted
      to normal values. Type IV patients, as a group, were distinguished by greater
      hyperglycemia and relative body weight. Chylomicronemia was not observed in this
      study group. Hyperlipoproteinemia was frequent in this adult-onset diabetic
      population and differed in several respects from similar data in untreated
      juvenile-onset diabetes reported by others.

PMID- 26309920
TI  - LEPROMATOUS LEPROSY AND AUSTRALIA ANTIGEN WITH COMMENTS ON THE GENETICS OF
      LEPROSY.

PMID- 26309921
TI  - Fiji, the Land of Smiles.

PMID- 26309922
TI  - Marion's Message. Birth, Safe Motherhood and the Human Future.

PMID- 26309923
TI  - Micro Wellness.

PMID- 26309924
TI  - Group B Streptococcal Infection: Beyond the Mysteries.

PMID- 26309925
TI  - When Pregnancy Goes SOUTH: Keeping Birth Gentle.

PMID- 26309926
TI  - Nipple Thrush: How to Identify and How to Treat.

PMID- 26309927
TI  - Unhurrying the Moment of Meeting.

PMID- 26309928
TI  - Crossing Borders with Andrea.

PMID- 26309929
TI  - Update on the Commonwealth of the Bahamas, a Caribbean Nation.

PMID- 26309930
TI  - The Beta Strep Dilemma.

PMID- 26309931
TI  - Breastfeeding Support at Yayasan Bumi Sehat: A Student Midwife's Reflections.

PMID- 26309932
TI  - Allowing the Labouring Mother to Be Primal.

PMID- 26309933
TI  - Healthy Pregnancy: Fish and Oils.

PMID- 26309934
TI  - After the Disaster: What Comes Next in the Philippines?

PMID- 26309935
TI  - Birth Funnies.

PMID- 26309936
TI  - Sarah Stone: An Early-modern English Midwife.

PMID- 26309937
TI  - Understanding the Infant Feeding Decision.

PMID- 26309938
TI  - Collaboration Is KEY.

PMID- 26309939
TI  - A Surrogate Birth Story.

PMID- 26309940
TI  - Positive Birth Changes in Cameroon.

PMID- 26309941
TI  - Mindfulness: An Intervention for Improving the Health of Mothers and Babies.

PMID- 26309942
TI  - The Revolution So Far.

PMID- 26309943
TI  - What are your protocols for handling GBS? Do you believe it is a true concern for
      pregnant mothers?

PMID- 26309944
TI  - Frontier Nursing University Press Release.

PMID- 26309945
TI  - Re: "The Paleo Lifestyle in Pregnancy:" Issue 112.

PMID- 26309946
TI  - Birth in Israel Update.

PMID- 26309947
TI  - Is the ADA still relevant?

PMID- 26309948
TI  - Q & A with Dr. Doroshow.

PMID- 26309950
TI  - To refund or not to refund?

PMID- 26309949
TI  - Meet Ted Borris. New CDS director of scientific programs.

PMID- 26309951
TI  - Sass N Style.

PMID- 26309952
TI  - Bob Banks reflects on a life of service.

PMID- 26309954
TI  - Keep fit.

PMID- 26309953
TI  - Have you seen an invisible man?

PMID- 26309955
TI  - The eccentricity of nurses.

PMID- 26309956
TI  - The standard you walk past is the standard you accept.

PMID- 26309957
TI  - Management of 'Do Not Attempt Cardiopulmonary Resuscitation' (DNACPR) decisions
      in the perioperative period.
AB  - It is increasingly common for patients to be scheduled for anaesthesia and
      surgery with a 'Do Not Attempt Cardiopulmonary Resuscitation' (DNACPR) decision
      in place. Updated guidelines for the implementation and management of DNACPR
      decisions were published jointly by the British Medical Association (BMA), the
      Resuscitation Council (UK) and the Royal College of Nursing (RCN) in 2014 (BMA,
      RC(UK), RCN 2014). The Association of Anaesthetists of Great Britain and Ireland
      (AAGBI) published specific guidelines in 2009 to guide the perioperative
      management of such patients (AAGBI 2009). In this article, we explain these
      guidelines with a focus on how DNACPR decisions are made and how they can be
      modified in order to permit appropriate surgery to take place.

PMID- 26309958
TI  - Part two: Qualitative research.
AB  - This second article in the series Spotlight on Research focuses on qualitative
      research, its applications, principles and methodologies. It provides an insight
      into how this approach can be used within the perioperative setting and gives
      advice for practitioners looking to undertake a qualitative research study.

PMID- 26309959
TI  - Acute pain management in the older person.
AB  - The proportion of older people in society is growing steadily. This particular
      group is more likely to be admitted to hospital and a number of papers have
      highlighted the inadequate or inappropriate assessment and management of their
      pain, particularly in the perioperative period. Pain relief is possible for the
      majority of people. This paper aims to give an overview of the assessment and
      management of pain in older people.

PMID- 26309960
TI  - Suture of a stab wound of the heart.
AB  - Over many centuries, from the early writings of Galen, 'the father of Medicine',
      wounds of the heart were considered fatal and outside the remit of surgery. With
      the advent of anaesthesia, (ether was introduced by William Morton in 1846) and
      of antiseptic surgery, (Joseph Lister's first publication was in 1867), there was
      an explosion in the surgery of the abdominal cavity, the chest, the skull and the
      limbs, yet the heart was considered by the surgical fraternity to be the 'no-go'
      area of the body. Theodor Billroth, Professor of Surgery in Vienna and himself a
      pioneer of modern surgery, (he performed the first successful partial gastrectomy
      for carcinoma of the stomach in 1881), wrote "the surgeon who would attempt to
      suture a wound of the heart should lose the respect of his colleagues". In
      London, Stephen Paget, in 1896, wrote: "No new method and no new discovery can
      overcome the natural difficulties that attend a wound of the heart. It is true
      that suture has been vaguely proposed as a possible procedure and has been done
      in animals but I cannot find that it has ever been attempted in practice". (In
      fact, the heart is an amazingly tough and efficient pump that goes on working,
      year after year, without ever stopping for a service!).

PMID- 26309961
TI  - [Legally mandated vaccination counseling is insufficient].

PMID- 26309962
TI  - [Implementing infant development supportive nursing in neonatology from the
      perspective of organizational consulting].

PMID- 26309963
TI  - [Abdominal wall defects: gastroschisis and omphalocele].

PMID- 26309964
TI  - [Professional association supports DAKJ petition. In focus: the rights of
      children and adolescents].

PMID- 26309965
TI  - [It rumbles and grumbles in children when dwarfs reside within them].

PMID- 26309966
TI  - [Protection against the sun's rays: prevention must already start the first year
      of life].

PMID- 26309968
TI  - [Camouflage and deception: how consumers tricked].

PMID- 26309969
TI  - [The importance of nonverbal communication].

PMID- 26309970
TI  - [Safe breast nipple care in breastfeeding].

PMID- 26309971
TI  - [Study shows: improved glycemic control in diabetes patients by correcting the
      injection technique].

PMID- 26309972
TI  - [About curse and blessing, having more than 2 parents].

PMID- 26309973
TI  - [Child grief support requires high quality standards].

PMID- 26309975
TI  - [The earlier, the better].

PMID- 26309974
TI  - [Legal liability for blindness in an extremely low birth weight premature
      infant].

PMID- 26309976
TI  - [The infection prone child - topic of the 4th Krefeld Day of Pediatric nursing].

PMID- 26309977
TI  - [Family friendliness - only empty concept?].

PMID- 26309978
TI  - [Letter to the editor about "Green tea with lemon: Suggestions for a good food
      combination" kks; 02/15, p. 65-67].

PMID- 26309979
TI  - [Palliative care for children in Berlin: Bjorn Schulz Foundation and Charite
      cooperate].

PMID- 26309980
TI  - [Interview about the book: New and Old Infectious Diseases].

PMID- 26309981
TI  - [Exchange with and in South Africa - there are still positions open...!].

PMID- 26309983
TI  - [Networking of prevention active family, health and pediatric nurses].

PMID- 26309984
TI  - [Making hemangiomas disappear with cardiac agents: pediatric surgeons greet the
      new study results].

PMID- 26309985
TI  - [Does coffee during pregnancy harm the baby?].

PMID- 26309986
TI  - [Lack of consensus about the best obstetric procedures in the European Union].

PMID- 26309987
TI  - [Study: surface disinfectants ineffective against viruses?].

PMID- 26309988
TI  - [On the trail of the healing effect of fasting].

PMID- 26309989
TI  - [We are worth it].

PMID- 26309990
TI  - [Nursing care inpatient facilities for nursing the disabled - a neglected topic
      up to now].

PMID- 26309991
TI  - [Transportation management of neonatal - pediatric transports].

PMID- 26309992
TI  - [Responsibilities in the assessment of congenital hip dislocation].

PMID- 26309993
TI  - [Optimal dosage].

PMID- 26309994
TI  - [Daisy Festival at St. Nicholas Children's Hospice - again with charity cross
      country run and kid's run].

PMID- 26309995
TI  - [Half marathon as self-experiment].

PMID- 26309996
TI  - [Professional politicians speak positively of a federal ombudsman for children].

PMID- 26309997
TI  - [I will then simply be gone].

PMID- 26309999
TI  - [Ticks lurk in the garden].

PMID- 26310000
TI  - [How diverticula are treated today].

PMID- 26310001
TI  - [Characteristic vitreous changes in congenital cataracts].
AB  - AIM: To analyze changes and identify specific signs of underdevelopment of the
      vitreous body in certain types of congenital cataracts. MATERIAL AND METHODS: A
      total of 26 patients (52 eyes) with congenital changes in the lens and vitreous
      were examined by means of digital spatial ultrasound imaging. RESULTS: On the
      basis of multiplanar ultrasound examination and three-dimensional virtual
      modelling of the eye, spatial ultrasonographic characteristics of combined
      congenital involvement of the lens and vitreous have been determined. The changes
      revealed are shown to be morphologically related. CONCLUSION: The results suggest
      three-dimensional digital ultrasound virtual modelling useful for studying
      combined congenital changes in the lens and vitreous and, thereby, it enables
      'decoding' of some elements of their normal morphology.

PMID- 26310002
TI  - [Effects of blood flow properties on ocular hemodynamics].
AB  - AIM: to study the effects of blood rheology on ocular blood flow (OBF) parameters
      and estimated individual normal range of intraocular pressure (IOP). MATERIAL AND
      METHODS: A total of 15 patients (15 eyes) taking warfarin were enrolled.
      Volumetric parameters and linear velocity of OBF under warfarin treatment and
      after its cessation were obtained by means of flowmetry (Paradigm's Blood Flow
      Analyzer) and color Doppler flow mapping (Voluson 730), respectively. On the
      basis of flowmetry results an individual normal range of IOP was calculated in
      all patients. RESULTS: Pulsatile OBF does not appear to correlate with warfarin
      induced changes in blood rheology (p = 0.09), however, depends on IOP
      fluctuations (p = 0.02). Resistance index of retinal vessels is found to rise
      significantly with increasing blood viscosity (p < 0.05). CONCLUSION: The use of
      warfarin, an indirect thrombin inhibitor, has no effect on estimated individual
      normal range of IOP, which is crucial for glaucoma diagnosis and monitoring.

PMID- 26310003
TI  - [Dry eye syndrome in patients with primary open-angle glaucoma].
AB  - AIM: to determine the frequency and severity of dry eye syndrome (DES) in primary
      open-angle glaucoma (POAG) patients that are newly diagnosed or already receiving
      beta blocker instillation therapy. MATERIAL AND METHODS: A total of 127 patients
      (190 eyes) with POAG were divided into two groups. Group 1 included 55 newly
      diagnosed patients (88 eyes), group 2-72 POAG patients (102 eyes) instilling
      timolol 0.5% twice daily into the affected eye. The control group included 20
      patients (40 eyes) aged 60-88 years (73.6 +/- 9.2 years on average) with early
      age-related cataract. RESULTS: DES was found in 69 POAG patients (79%) who was
      just starting their topical hypotensive therapy and 85 of those (84%) under
      treatment (p = 0.39). CONCLUSIONS: One should take into account when prescribing
      ocular hypotensive therapy that newly diagnosed POAG patients usually already
      suffer from a dry eye. The use of topical beta blockers that contain
      preservatives exacerbates dry eye signs and symptoms in these patients.

PMID- 26310004
TI  - [Evaluating the efficacy of anti-VEGF therapy in patients with exudative age
      related macular degeneration and concomitant glaucoma].
AB  - AIM: to evaluate the efficacy of anti-VEGF therapy in patients with exudative age
      related macular degeneration (AMD) and glaucoma. MATERIAL AND METHODS: The study
      enrolled 117 patients (117 eyes) with exudative AMD and concomitant non-operated
      primary open-angle glaucoma (POAG). All patients were divided into several groups
      depending on their intraocular pressure (IOP) and stage of POAG. Hypotensive
      therapy included carbonic anhydrase inhibitors, beta-adrenergic antagonists (beta
      blockers) and alpha(2)-adrenergic agonists (alpha-2 mimetics). Lucentis
      (ranibizumab) was intravitreally injected thrice at monthly intervals. All
      patients underwent a standard ophthalmic examination, fluorescent retinal
      angiography, and optical coherence tomography. IOP was measured before the first
      and after the last injection by means of Icare PRO reboud tonometer. RESULTS:
      There was no statistically significant difference between groups Ia, IIa, Ib, and
      IIb in terms of IOP elevation. Glaucoma IIc and IIIa patients showed just a
      moderate increase in IOP that did not require regimen adjustment. There was,
      however, a single IIIb case of persistent IOP elevation, in which one-step
      penetrating trabeculectomy with intravitreal ranibizumab injection was later
      performed. Resolution of macular edema was achieved in all patients. Visual
      acuity (VA) varied between the groups demonstrating a tendency toward improvement
      in glaucoma Ia patients (p = 0.062) and stabilization in glaucoma IIa (p = 0.61),
      Ib (p = 0.07), and IIb (p = 0.29) patients. In some cases of low vision at
      baseline and subretinal fibrosis, VA changes were of no clinical significance.
      CONCLUSIONS: Intravitreal ranibizumab therapy proved effective in exudative age
      related macular degeneration with concomitant glaucoma. Timely treatment of both
      AMD (i.e. before the development of subretinal fibrosis) and glaucoma contributes
      to therapeutic success in these patients.

PMID- 26310005
TI  - [Results of the use of antioxidant and angioprotective agents in type 2 diabetes
      patients with diabetic retinopathy and age-related macular degeneration].
AB  - AIM: to investigate changes in clinical, functional, and morphological parameters
      of the retina in type 2 diabetes patients with diabetic retinopathy (DR) and
      those with combined fundus pathology (DR plus age-related macular degeneration
      (AMD)) before and after a course of antioxidants and angioprotectors in the form
      of mono- or combination therapy. MATERIAL AND METHODS: The study included 180
      patients (180 eyes) with type 2 diabetes divided into 6 groups of 30 each. DR was
      graded according to E. Kohner and M. Porta classification, AMD--AREDS
      classification. Thus, group 1 consisted of patients with DRO,; group 2--DR1
      without DM, group 3--DR1 with DM, group 4--DRO and "dry" AMD (AREDS 1-3), group 5
      -DR1 with no DM but with AMD (AREDS 1-3), and group 6--DR1 with DM and AMD (AREDS
      1-3). A drug containing lutein 6 mg, zeaxanthin 0.5 mg, vitamin C 60 mg, vitamin
      E 7 mg, vitamin A 1.5 mg, vitamin B2 1.2 mg, rutin 25 mg, zinc 5 mg, selenium 25
      mcg, and bilberry extract 60 mg was used for antioxidative therapy. Ginkgo biloba
      leaf extract 60 mg was chosen as the angioprotector. In all patients visual
      acuity, macular thickness and morphology (OCT) as well as light sensitivity
      (microperimetry) were assessed before and after the treatment course. RESULTS:
      Analysis of baseline measurements demonstrated a significant decrease in best
      corrected visual acuity (p < 0.05) in study groups 2-6 as compared with group 1.
      Macular thickness was increased in all groups, however, the changes were
      statistically significant only in groups 3 and 6 (p<0.05). Light sensitivity of
      the macula showed a reduction, which was statistically significant in groups 4-6
      (p < 0.05). After the course of antioxidant and angioprotective therapy, these
      parameters improved in all groups. The greatest effect was achieved with
      simultaneous antioxidant and double-dose angioprotective therapy (240 mg per
      day): visual acuity increased significantly (p < 0.05) in all groups except group
      1; macular thickness decreased in all groups, however, the changes were
      statistically significant (p < 0.05) only in groups 1-3 and 5; light sensitivity
      also improved in all groups, significantly (p < 0.05) in groups 1-3 and 4.
      CONCLUSIONS: Extended analysis of clinical, functional and morphological changes
      in the retina at the onset of DR in type 2 diabetes patients with concomitant
      "dry" AMD enables timely diagnosis, prognosis, prevention, and early treatment.
      Conservative treatment with antioxidant and angioprotective agents has been
      proved effective in type 2 diabetes patients with preclinical (DRO) and early
      (DR1) diabetic retinopathy and those with DR and "dry" AMD (AREDS 1-3) in terms
      of functional and morphological parameters of the retina. From all the regimens,
      a combined antioxidant and double-dose angioprotective (240 mg) therapy appeared
      to be the most effective and can be considered not only a preventive, but also a
      therapeutic measure in type 2 diabetes patients with initial stages of DR (DRO,
      DR1) or those with DR and DM or combined DR and AMD (AREDS 1-3).

PMID- 26310006
TI  - [Ultrasound biomicroscopy findings in the area of previous surgical intervention
      in refractory glaucoma patients under topical ocular hypotensive therapy].
AB  - AIM: to evaluate the effectiveness of different classes of topical hypotensive
      medications in refractory primary open-angle glaucoma (POAG), judging from
      structural changes in artificial pathways for intraocular fluid (IOF) visualized
      with ultrasound biomicroscopy (UBM). MATERIAL AND METHODS: UBM analysis was
      performed in 104 eyes of 102 patients, mean age 68.4 +/- 0.8 years, including 41
      POAG patients with well controlled intraocular pressure (IOP) (group 1) and 41
      refractory POAG patients with poorly controlled IOP (group 2), all under topical
      hypotensive therapy (prostaglandin analogues, beta blockers, carbonic anhydrase
      inhibitors, or combination drugs). The control group consisted of 20 patients,
      who maintained normal IOP after a single glaucoma surgery and did not require
      medical management. RESULTS: The following UBM parameters were evaluated:
      intrascleral cavity and filtering bleb heights and conjunctival and scleral flap
      thicknesses. Findings differed depending on the condition of IOF outflow
      pathways. Unlike the poorly controlled patients, UBM parameters in group 1 were
      comparable to those in the controls. The optimal control of postoperative IOP was
      achieved on combination therapy (a beta blocker plus a carbonic anhydrase
      inhibitor). CONCLUSION: In contrast to well controlled POAG patients, target
      values of IOP were not achieved in refractory POAG patients with either of the
      topical therapeutic measures. Moreover, intrascleral cavity and filtering bleb
      heights in these patients were reliably low (p <= 0.01), as confirmed by UBM
      analysis of the area of surgical intervention.

PMID- 26310007
TI  - [Results of combined endotrabeculectomy and phacoemulsification surgery].
AB  - AIM: to identify indications and evaluate the efficacy of combined
      endotrabeculectomy and phacoemulsification surgery. MATERIAL AND METHODS: A total
      of 172 patients (193 eyes) with open-angle glaucoma and cataract were enrolled.
      Group 1 included 102 patients (118 eyes), who were considered surgical candidates
      due to decompensation of IOP, group 2--70 patients (75 eyes), in whom IOP control
      could only be achieved with a multidrug regimen (two or more ocular hypotensive
      medications). The mean preoperative IOP measured with Maklakov tonometer was 26.4
      +/- 1.8 mmHg in group 1 and 20.5 +/- 1.7 mmHg in group 2. In 134 eyes the extent
      of retention of intraocular fluid was determined intraoperatively by provoking
      blood reflux into Schlemm's canal. RESULTS: In 6 out of 134 eyes (4.5%) Schlemm's
      canal was not at all filled with blood, which was considered a contraindication
      for endotrabeculectomy. Partial filling of Schlemm's canal with blood was
      observed in 26 out of 134 eyes (19.4%), complete--in 102 eyes (76.1%). All but 6
      patients underwent endotrabeculectomy (ab interno trabecular excision with
      original forceps through the anterior chamber angle) combined with cataract
      phacoemulsification and intraocular lens implantation. In 11 out of 126 cases,
      insignificant bleeding occurred during sample acquisition. No other complications
      were registered. Six months after the surgery, IOP was reduced by the mean of 7.0
      +/- 0.6 mmHg (26.5% from the baseline) in group 1 and by 2.2 +/- 0.2 mmHg (10.7%
      from the baseline) in group 2. The number of hypotensive medications by that time
      has been decreased from 2.3 +/- 0.3 to 0.8 +/- 0.2 in group 1 and from 1.6 +/-
      0.3 to 0.4 +/- 0.1 in group 2. CONCLUSION: Combined endotrabeculectomy and
      phacoemulsification surgery is a pathogenically oriented procedure, which
      improves ocular hydrodynamics and has a significant hypotensive effect.

PMID- 26310008
TI  - [Modified technique of hybrid phacoemulsification].
AB  - AIM: to develop a modification to hybrid phacoemulsification (PE) that would
      involve the use of femtosecond laser. MATERIAL AND METHODS: Modified hybrid PE
      was performed in 225 patients (267 eyes) with grade II-IV lens nuclei in terms of
      their density. Conventional PE was performed in 237 patients (278 eyes). RESULTS:
      By utilizing the suggested technique of PE, one can avoid certain problems of
      conventional surgery and optimize the steps of nucleus fragmentation and
      emulsification. CONCLUSIONS: The suggested modification to hybrid PE enables
      effective removal of grade II-V cataract lenses at minimum ultrasonic load.

PMID- 26310009
TI  - [Differentiated approach to hybrid phacoemulsification in small pupils].
AB  - AIM: to develop a differentiated approach to hybrid phacoemulsification (PE) in
      small pupils. MATERIAL AND METHODS: Modified hybrid PE was performed in 119
      patients (130 eyes) with conditionally small pupils (preoperative dilated pupil
      diameter of less than 5.5 mm). RESULTS: A differentiated approach to hybrid PE
      has been developed and tested in patients with poor preoperative mydriasis.
      CONCLUSIONS: Small rigid pupils are considered a relative contraindication for
      hybrid PE. Developed modifications enable less surgical trauma and changes in
      efficient exposure time, while the latter is usually increased in standard PE in
      patients with poor preoperative pupil dilation.

PMID- 26310010
TI  - [Analyzing causes for opacification of acrylic IOLs].
AB  - AIM: to study the nature of intraocular lens (IOL) opacification depending on the
      patient's ocular status and general condition. MATERIAL AND METHODS: A total of 9
      patients (9 eyes) with 3-6 year history of progressive IOL opacification were
      enrolled. All the IOLs were acrylic (either hydrophilic--7 cases, or hydrophobic-
      2 cases). Two patients had their IOLs exchanged due to opacification. Six
      patients earlier underwent glaucoma surgery. Two patients were type 2 diabetic.
      Slit lamp biomicroscopy and optical microscopy were used for IOL examination.
      RESULTS: The surface of hydrophilic acrylic lenses appeared bumpy because of
      multiple variously shaped translucent granules separated by a chaotic network of
      furrows and microfractures and located predominantly in the optic zone. In a more
      severe case, a bowl-shaped impression was observed in the area of opacification.
      Surface changes of hydrophobic acrylic lenses were in the form of isolated and
      confluent glistening formations (microcavities). CONCLUSION: Signs of IOL
      degradation develop over a long period of time (3-6 years, in our experience) and
      mostly involve the anterior surface of the lens optic. Ocular comorbidity,
      glaucoma in particular, as well as other surgery and/or therapeutic treatment
      following IOL implantation may contribute to its opacification. Analysis of
      published data and own observations suggest that hydrophobic IOLs should be
      preferred in patients with concomitant diseases, especially diabetes mellitus.
      Granular deposits, if accumulate, may lead to deformation of the lens optic, as
      confirmed by the bowl-like impression in one of the explanted hydrophilic IOLs.

PMID- 26310011
TI  - [Effects of dexamethasone and superoxide dismutase instillations on clinical
      course of uveitis and local biochemical processes (experimental study)].
AB  - AIM: to evaluate and compare the effect of topical superoxide dismutase (SOD),
      which is an antioxidant enzyme, dexamethasone, and a combination of these on the
      course of experimental uveitis in rabbits as well as biochemical parameters of
      aqueous and vitreous humor. MATERIAL AND METHODS: Acute uveitis was induced in 16
      rabbits by a double injection (subcutaneous and intravitreal) of normal horse
      serum. Of them 12 animals, divided into 3 groups of 4 each, received topical SOD,
      dexamethasone, or both daily for 7 days. The remaining 4 rabbits (8 eyes) were
      treated with placebo and, thus, constituted the control group. On day 8 the
      following parameters were measured in aqueous humor: protein concentration,
      antioxidant activity, SOD activity, alpha2-macroglobulin level, and leukocyte
      number. Total protein and albumin levels in vitreous humor were also determined.
      RESULTS: The effects of SOD and dexamethasone instillations were considered
      similar in many parameters. However, SOD was associated with a greater increase
      in antioxidant activity and a greater decrease in aqueous humor leukocytes, while
      dexamethasone was more effective in decreasing aqueous humor alpha2-macroglobulin
      and vitreous humor protein and albumin. The substances had a synergistic effect
      on iridal edema as well as aqueous humor leukocyte number and alpha2
      macroglobulin level. CONCLUSION. Adding SOD to the complex therapy of uveitis
      results in lower inflammation intensity and enhanced dexamethasone effect.

PMID- 26310012
TI  - [Evaluating the effectiveness of Solanum tuberosum shoots extract in experimental
      ocular herpes].
AB  - Ocular herpes (OH) is an infectious disease caused by the herpes simplex virus
      (HSV) characterized by a variable clinical presentation and often accompanied by
      complications that may lead to deterioration of visual functions, cataract
      development, or even blindness. Its treatment is arduous. The aim of this work
      was to evaluate the effectiveness, tolerability, and safety of Panavir eye drops
      in a rabbit model of OH. MATERIAL AND METHODS: Ocular infection was induced with
      HSV-1 (EU strain) in grey rabbits (all males, 2.5-3.0 kg) according to the
      standard technique. The treatment included Panavir-GLA (Panavir-gamma-linolenic
      acid) and Panavir medications. RESULTS: Panavir eye drops instilled 6 times daily
      for 8 days showed a pronounced therapeutic effect and prevented the development
      of severe corneal opacities. The most rapid and significant results were seen in
      rabbits with epithelial keratitis and those with short-term persistence of the
      virus. Generally, the effectiveness of Panavir eye drops was comparable with that
      of the reference drug (Oftalmoferon). Panavir instillations caused no irritation,
      toxic and/or allergic effects and were well tolerated by the rabbits. CONCLUSION:
      The data obtained suggest that Panavir eye drops may be included in OH treatment
      schemes.

PMID- 26310013
TI  - [Non-Hodgkin lymphoma (a case of simultaneous ocular and orbital involvement)].
AB  - The paper presents an integrated analysis of clinical, instrumental, and
      morphological data on a very rare pathological condition-- simultaneous ocular
      and orbital involvement in a lymphoproliferative disorder.

PMID- 26310014
TI  - [Vogt-Koyanagi-Harada syndrome (clinical cases)].
AB  - OBJECTIVE: to analyze two female cases of Vogt-Koyanagi-Harada (VKH) syndrome.
      MATERIAL AND METHODS: The first patient presented with bilateral panuveitis and
      unilateral keratomalacia (left eye). For the latter, blepharorrhaphy was
      performed. Methylprednisolone (Metypred) and azathioprine pulses, subsequently
      switched to oral therapy, caused regression of uveitis. In 1 month the patient
      was operated for retinal detachment and associated cataract in her right eye. The
      second patient presented with bilateral detachment of neuroepithelium. Complete
      reattachment in both eyes was achieved with Metypred pulses followed by oral
      prednisolone and azathioprine. Bilateral panuveitis with pupil occlusion
      developed 6 months after the cessation of prednisolone, however, began to resolve
      as soon as the treatment was resumed. RESULTS: Timely diagnosis and combination
      pulse therapy (methylprednisolone and azathioprine) enabled rapid resolution of
      acute condition. CONCLUSIONS: Pulse Metypred is the mainstay of the treatment of
      VKH syndrome. Supplementing the treatment of autoimmune uveitis with low doses of
      azathioprine slows progression of the disease and minimizes prednisolone-induced
      side effects. It is important that VKH patients are treated with pathogenetic
      therapy in close cooperation with an immunologist. Long-term monitoring (not less
      than 2-3 years) is also necessary.

PMID- 26310015
TI  - [Optogenetics and prosthetic treatment of retinal degeneration].
AB  - This is a review of the current state of optogenetics-based research in the field
      of ophthalmology and physiology of vision. Optogenetics employs an
      interdisciplinary approach that amalgamates gene engineering, optics, and
      physiology. It involves exogenous expression of a light-activated protein in a
      very particular retinal cell enabling regulation (stimulation vs. inhibition) of
      its physiological activity. The experience with gene therapy came in very useful
      for optogenetics. However, unlike gene therapy, which is aimed at repairing
      damaged genes or replacing them with healthy ones, optogenetics is focused on
      protein genes delivery for further molecular control of the cell. In retina, the
      loss of photoreceptors is not necessarily followed by neuronal loss (at least
      ganglion cells remain intact), which determines the practicability of prosthetic
      treatment. Clinical trials can now be considered, owing to the first successful
      conversion of ganglion cells of mouse degenerative retinas into artificial
      photoreceptive cells with ON and OFF receptive fields, which is crucial for
      spatial vision. The following issues are reviewed here in detail: 1. Choice of
      cell targets within the degenerative retina. 2. Strategy of utilizing the
      existing light-sensitive agents and development of new optogenetic tools. 3. Gene
      delivery and expression in retinal cells. 4. Methods of evaluating the treatment
      success. 5. Selection criteria for optogenetic prosthetics. The conclusion
      discusses currently unsolved problems and prospects for optogenetic approaches to
      retinal prosthetics.

PMID- 26310016
TI  - [RET/PTC Gene Rearrangements in the Sporadic and Radiogenic Thyroid Tumors:
      Molecular Genetics, Radiobiology and Molecular Epidemiology].
AB  - A review of molecular genetic, radiobiological and molecular epidemiological
      studies of gene (chromosome) rearrangements RET/PTC in the cells of the thyroid
      gland as well as the laws in relation to radiation exposure in vitro, in vivo and
      human populations identified with them are submitted. The data on the c-RET gene
      and its chimeric constructs with the gene-donors (RET/PTC rearrangements) are
      considered. The information about the history of the RET/PTC discovery, their
      types, carcinogenic potential and specificity both to tumor and non-tumor thyroid
      disease especially for papillary thyroid carcinoma are provided. The data (seven
      studies) on the induction of RET/PTC after irradiation of tumor and normal
      thyroid cells in vitro and mice are reviewed. The mechanisms of RET/PTC induction
      may be associated with DNA double strand breaks and oxidative stress. Some
      information (three publications) about the possibility of RET/PTC induction by
      low doses of radiation with low LET (to 0.1 Gy) is given and it is concluded that
      their potential evidentiary is generally weak. The achievements in the molecular
      epidemiology of RET/PTC frequency for exposed and unexposed cohorts are stated.
      At the same time it is noted that, despite the vast array. of data accumulated
      from 30 countries of the world and more than 20 years of research, the formed
      provisions are weakly confirmed statistically and have no base corresponding to
      the canons of evidence-based medicine. The possibility of use of the RET/PTC
      presence or their frequencies as markers of the papillary thyroid carcinomas and,
      specifically, their radiogenic forms, is considered. In the first case the answer
      may be positive, while in the second, the situation is characterized by
      uncertainty. Based to the above mentioned we came to a conclusion about the need
      of a pooled or meta-analysis of the totality of the published data.

PMID- 26310017
TI  - [Radioprotective Properties of NO-Synthase Inhibitor T1023: I. Indicators of
      Radioprotective Activity and Interaction with Other Radioprotectors].
AB  - The study of radioprotective activity of NO-synthase inhibitor, N-S-isothiourea
      derivative T1023 showed that this compound has a significant therapeutic range of
      radioprotective activity (5.5-6.0) and its optimal radioprotective dose is 1/4
      LD16. The value of its Radiation Dose-Reduction Factor totaled 1.4-1.8. We have
      demonstrated a pronounced pharmacodynamic interaction of T1023 with some known
      radioprotectors. The character of the interaction was determined by its
      vasoactive properties. Combined use of T1023 and cystamine, which causes a
      decrease in vascular tone, was accompanied by a statistically significant
      weakening of the radioprotective effect. But, the combined use of T1023 with
      serotonergic and adrenergic radioprotectors having a pressor action caused a
      statistically significant increase in the radioprotective effect. Moreover, T1023
      combined with such radioprotectors caused the synergistic radioprotective effect
      even when used at small doses that do not have any radioprotective effect alone.
      The findings suggest that NOS inhibitors can be effective radioprotectors and are
      able to create new opportunities for the development of safer radioprotective
      agents. The very same compound T1023, according to current criteria of
      pharmacological screening, is certainly promising for further investigations.

PMID- 26310018
TI  - [Radioprotective Properties of NO-synthase Inhibitor T1023: II. The Ability for
      Selective Protection of Normal Tissues During Radiotherapy of Tumors].
AB  - We studied the effect of T1023, NO-synthase inhibitor, N-acyl-S-alkyl-isothiourea
      in a single administration at a dose of 75 mg/kg on the growth of transplantable
      rat sarcoma M-1 and the development of acute skin reactions after the local
      impact of gamma-radiation at the doses of 32 and 36 Gy. The results showed that
      the T1023 at a single dose had no effect on the growth of sarcoma, and did not
      modify the radiosensitivity of the tumor and anti-tumor efficacy of gamma-rays.
      However, at both doses T1023 significantly reduced the severity of acute
      radiation skin reactions. NOS inhibitor did not change the duration of the
      inflammatory and regenerative processes, but significantly limited the degree of
      radiation alteration of the deep layers of the skin and underlying tissues. The
      findings suggest that the hypoxic mechanism of antitumor action allows T1023 to
      selectively protect the non-malignant tissue during radiation therapy of solid
      tumors. Therefore, this compound may be regarded as a promising basis for the
      development of pharmacological prevention of radiotherapy complications.

PMID- 26310019
TI  - [Evaluation of Reproductive Health of Chickens and Their Progeny at a Chronic
      Effect of 131I].
AB  - A reproductive health of hens exposed to 131I in a 30-day period with daily
      quantities ranging from 0.11 to 4.6 MBq/kg and 6 progenies of their offspring was
      evaluated. We determined that 131I did not change significantly the reproductive
      potential of hens if administered at a dose of 0.11 MBq, while it raised at 1.1
      MBq, progressively decreased after a short-time increase at 2.1 MBq and was
      inhabited up to its irreversible extinction at 4.6 MBq. Irrespective of the
      isotope quantity administered, a decline occurred in the birth rate of the
      progeny where hens dominated in the sex composition. The reproductive potential
      (i.e., laying capacity) of the offspring of three chicken progenies that had been
      administered 131I at 0.11 MBq/kg, progenies 3 and 5 that had been administered
      1.1 MBq/kg and progeny 1 affected with 2.1 MBq/kg increased, while for chicken
      progenies 1, 2, 4 and 6 that had been given 131I at 1.1. MBq/kg the reproductive
      capacity was within the normal range or decreased.

PMID- 26310020
TI  - [Composition and Density of Soil Fauna in the Region with Enhanced Radioactivity
      Level (Komi Republic, Vodnyi)].
AB  - Studies on the influence of high levels of radiation on soil fauna were carried
      out in 2012 in the territory formed as a result of the activity of the enterprise
      for extraction and production of radium from reservoir water and waste of uranium
      ore from 1931 to 1956. At present the local radioactive pollution in this area is
      caused by the presence of heavy natural radionuclides 226Ra, 238U and products of
      their disintegration in soils. The oppression of soil invertebrate.fauna in pine
      forests and meadows with high levels of radionuclides and heavy metals is
      revealed. Also shown is the decrease in the number and density of different
      taxonomic groups of invertebrates, reduction of the diversity and spectrum of
      trophic groups and vital forms in the area with a high content of radionuclides
      in soil. Our results are in agreement with the results obtained by the similar
      studies showing negative influence of high-level ionizing radiation on soil
      fauna.

PMID- 26310021
TI  - [Microbiological Aspects of Radioactive Waste Storage].
AB  - The article gives information about the microorganisms inhabiting in surface
      storages of solid radioactive waste and deep disposal sites of liquid radioactive
      waste. It was shown that intensification of microbial processes can lead to
      significant changes in the chemical composition and physical state of the
      radioactive waste. It was concluded that the biogeochemical processes can have
      both a positive effect on the safety of radioactive waste storages
      (immobilization of RW macrocomponents, a decreased migration ability of
      radionuclides) and a negative one (biogenic gas production in subterranean
      formations and destruction of cement matrix).

PMID- 26310022
TI  - [Dynamics of Radioecological State of the Fresh-Water Ecosystems Affected by a
      Long-Term Impact from Nuclear Power Plant in the Frontiers of the Zone under
      Observation].
AB  - The results of radioecological studies of six small rivers situated in the
      surveillance zone of the Beloyarskaya NPP (BNPP) and around the cooling pond of
      the power plant are presented. 21 radionuclides and the total alpha- and beta
      activity were studied in the main components of the aquatic ecosystems. It is
      shown that after the 1st and 2nd BN PP blocks decommissioning the content of 60Co
      and 137Cs in the Beloyarskoye storage pond water, sediments, fish fauna and
      macrophytes dropped tens and hundreds of times. The fundamental importance of
      this fact is that in a large range of time the aquatic ecosystem mechanism of
      self-purification from radionuclides is working due to radioactive substances
      decay as well as redistribution of radionuclides from water to other components,
      primarily to the sediments. Of 6 small rivers the maximum levels of radioactive
      substances is found in the river Olkhovka, which for several years has been
      subjected to the low-level radioactive water discharges from Beloyarskaya NPP.
      The radionuclide content in the main components of the aquatic ecosystems of the
      other five rivers studied after BNPP 47-year operation period corresponds to the
      regional background.

PMID- 26310023
TI  - [S.I. Auerbach--an Outstanding Scientist and Organizer of Radioecological
      Research (on the 10th Anniversary of Death) (1922-2004)].

PMID- 26310024
TI  - [Main Results of Scientific Research in the Field of Radiation Biology and
      Radiation Ecology in 2014].

PMID- 26310025
TI  - [The XLIII Radiological Readings Named after V.M. Klechkovsky].

PMID- 26310026
TI  - [On the Birthday Anniversary of Victor Georgievich Vladimirov].

PMID- 26310027
TI  - [Ancient DNA: Results and Prospects (the 30th Anniversary)].
AB  - Evolutionary genetics has reached a new level of research thanks to the
      opportunity to study the genomes of not only present-day but also of ancient
      organisms. The obtaining of reliable data when working with ancient DNA is
      possible only in the case of interdisciplinary collaboration between
      archaeologists, paleontologists, molecular geneticists, and bioinformaticians.
      Despite laborious and high-cost technologies, the results never cease to amaze
      and can not only fill the gaps in the knowledge of the evolutionary history of
      different species but can also review the existing ideas on population
      development and dynamics. In this review, we discuss the history of the
      development of investigative techniques in ancient DNA research and the most
      striking results of these studies, including the most recent achievements.

PMID- 26310028
TI  - [Evolutionary and Genetic Roots of Hypertensive Disease].
AB  - This review concerns issues related to the evolutionary and genetic origins of
      hypertensive disease. An evolutionary approach is used to account for the
      predisposition of modern people to the development of a pathology such as
      hypertensive disease. Many studies indicate the importance of "ancestral"
      alleles, which provided perfect adaptation to the environment and lifestyle of
      our distant relatives, with respect to the increase in hypertensive disease
      development among modern individuals.

PMID- 26310029
TI  - [Symbiogenesis and Synthetic Evolutionary Theory: The Third Synthesis].
AB  - Integration of the concepts of symbiogenesis and synthetic evolutionary theory is
      the main path for the development of evolutionary biology. It is based on the
      analysis of cooperative adaptations that evolve under the impact of symbiotic
      specific selective pressures responsible for the formation of super-species
      hereditary systems--metagenomes, symbiogenomes, and hologenomes. The genetic
      integration of nonrelated organisms (symbiogenesis) is determined by the
      inheritance of microsymbionts by hosts resulted in the complication of
      mutualistic interactions according to the scheme: pleiotropic symbiosis -->
      mutual partner's exploitation --> interspecies altruism. This evolution may
      result in the loss of genetic individuality in microsymbionts; this loss is
      expressed as a deep reduction in their genomes. A significant number of these may
      be exported to the host, resulting in the transformation of symbiotic systems
      into novel, genetically integral organisms.

PMID- 26310030
TI  - [Methylation in the Regulation of the Expression of Chromosome 3 and microRNA
      Genes in Clear-Cell Renal Cell Carcinomas].
AB  - The methylation of CpG islands in promoter regions, together with the interaction
      of miRNAs with the mRNAs of their target genes on the posttranscriptional level,
      are complex epigenetic mechanisms that perform the delicate and dynamic
      regulation of genes and signal transduction pathways in the cell. This review
      summarizes the results obtained by the authors, as well as the literature data,
      on the roles of methylation in regulating the protein-coding genes of chromosome
      3 and a number of miRNA genes in clear-cell renal cell carcinomas. The results
      are based on the use of genomic NotI-microarrays (which allow the identification
      of both methylation and deletions in genes containing CpG islands) and on some
      other approaches. The application of NotI-microarray technology to the analysis
      of the chromosome-3 short arm, a region of frequent deletions in tumors, gave us
      the opportunity to identify many novel genes associated with kidney cancer
      pathogenesis. The relationship between alterations in the expression leyels and
      methylation of chromosome 3 genes, kidney cancer progression, and metastasis was
      shown. New microRNAs involved in kidney cancer pathogenesis were identified as
      well. The functions of microRNA genes methylated in kidney cancer were discussed.

PMID- 26310031
TI  - [Influence of limk1 Gene Polymorphism on Learning Acquisition and Memory
      Formation with pCREB Distribution and Aggregate Formation in Neuromuscular
      Junctions in Drosophila melanogaster].
AB  - We have shown previously that the polymorphic structure of the limk1 gene in
      drosophila leads to changes in LIMK1 content and to defects in courtship
      behavior, sound production, and learning/memory. The results of the present study
      of three wild-type strains and mutant agn(ts3) with altered limk1 structure
      demonstrate that long-term memory is normal in Canton-S and Oregon-R but is
      impaired in Berlin and drastically suppressed in agn(ts3). This temperature
      sensitive mutant carries the S-element from the Tc1/mariner family insertion near
      the dlimk1 3'-UTR and, compared to Canton-S, has a reverse pCREB distribution in
      adult neuromuscular junctions (NMJ) of the second dorsal imago nerve before and
      after learning. Moreover, only agn(ts3) demonstrates amyloid-like aggregate
      formation in NMJ. This suggests that this impedes pCREb transport and thereby
      impairs the formation of short- and long-term memory.

PMID- 26310032
TI  - DEVELOPMENT AND ASSESSMENT OF EST-SSR MARKER FOR THE GENETIC DIVERSITY AMONG
      TOBACCOS (Nicotiana tabacum L.).
AB  - Because of the advantages of EST-SSR markers, it has been employed as powerful
      markers for genetic diversity analysis, comparative mapping and phylogenetic
      studies. In this study, a total of 429,869 tobacco (Nicotiana tabacum L.) ESTs
      were downloaded from the public databases, which offers an opportunity to
      identify SSRs in ESTs by data mining, and 38,165 SSRs were identified from
      379,967 uni-ESTs with the frequency of one SSR per 5.52 kb. Mono- and tri
      nucleotide repeat motifs were the dominant repeat types, accounting for 40.53 and
      34.51% of all SSRs, respectively. After eliminating mononucleotide-containing
      sequences, 86 pairs of primers were designed to amplify in four tobacco
      accessions. Only 15 primers (17.44%) showed polymorphism, and then they were
      further used to assess genetic diversity of 20 tobacco accessions. Unweighted
      pair-group method with arithmetic average dendrograms (UPGMA) and principal
      coordinates analysis plots (PCA) revealed genetic differentiation between N.
      rustica and N. tabacum, and between oriental tobacco and other accessions of N.
      tabacum. The present study reported the development of EST-SSR markers in tobacco
      by exploiting EST databases, and confirmed the effective way to develop markers.
      These EST-SSRs can serve in studies on cultivar identification, genetic diversity
      analysis, and genetics in tobacco.

PMID- 26310033
TI  - [Genetic Variation of the mtDNA cyt b Locus in Graylings (Thymalus sp.:
      Thymalidae, Pisces) Introduced into the Baydrag Gol River of the Valley of Lakes
      Basin (Mongolia)].
AB  - Based on sequence variation of the mtDNA cyt b gene, an analysis of graylings
      introduced from the Arctic Ocean basin (Selenga River basin) into one of the
      rivers of Central Asian inland basin (Baydrag Goal River of the Valley of Lakes
      basin) was carried out. Morphological and molecular genetic identification was
      performed, and it was established that the introduced species corresponded to the
      Baikal grayling. The relationships among Central Asian grayling species are
      discussed.

PMID- 26310034
TI  - [Genetic Structure of the Common Shrew Sorex araneus L. 1758 (Mammalia,
      Lipotyphla) in Continuous and Fragmented Areas].
AB  - In this work the genetic variability of the common shrew populations Sorex
      araneus L. in Eastern Europe was studied via sequencing of the mitochondrial gene
      cyt b. A total of 82 sequences of the mitochondrial gene cyt b with a length of
      953 basepairs were analyzed, including five chromosome races in a continuous area
      of the species in forest zone and two races in fragmented area in the steppe
      zone. Phylogeographic subdivision of the common shrew was not expressed, and
      there was no significant correlation between genetic and geographic distances in
      continuous areas. We did not acquire convincing evidence of the influence of
      narrow hybrid zones between chromosome races on the flow of neutral alleles. A
      significant p-distance (0.69 +/- 0.27%) of geographically close populations of
      the chromosome race Neroosa indicates the formation of the karyotype of this race
      in the Pliocene or Pleistocene. In our work, the phylogeographic structure was
      determined more by species area fragmentation than by its karyotypic features.

PMID- 26310035
TI  - [Genetic Variability and Structure of SNP Haplotypes in the DMPK Gene in Yakuts
      and Other Ethnic Groups of Northern Eurasia in Relation to Myotonic Dystrophy].
AB  - The genetic variability of the DMPK locus has been studied in relation to six SNP
      markers (rs2070736, rs572634, rs1799894, rs527221, rs915915, and rs10415988) in
      Yakuts with myotonic dystrophy (MD) in the Yakut population and in populations of
      northern Eurasia. Significant differences were observed in the allele frequencies
      between patients and a population sample of Yakuts for three SNP loci (rs915915,
      rs1799894, and rs10415988) associated with a high chance of disease
      manifestation. The odds ratios (OR) of MD development in representatives of the
      Yakut population for these three loci were 2.59 (95% CI, p = 0,004), 4.99 (95%
      CI, p = 0.000), and 3.15 (95% CI, p = 0.01), respectively. Haplotype TTTCTC,
      which is associated with MD, and haplotype GTCCTT, which was observed only in
      Yakut MD patients (never in MD patients of non-Yakut origin), were revealed. A
      low level of variability in the locus of DMRK gene in Yakuts (H(e) = 0.283)
      compared with other examined populations was noted. An analysis of pairwise
      genetic relationships between populations revealed their significant
      differentiation for all the examined loci. In addition, a low level of
      differentiation in territorial groups of Yakut populations (F(ST) = 0.79%), which
      was related to the high subdivision of the northern Eurasian population (F(ST) =
      11.83%), was observed.

PMID- 26310036
TI  - MASSIVE TRANSFUSION PROTOCOL: STANDARDIZING CARE TO IMPROVE PATIENT OUTCOMES.
AB  - Providing rapid response is a primary goal when caring for surgical patients with
      injuries involving massive blood loss. Massive transfusion protocols have been
      developed in some tertiary care health care facilities to ensure a rapid and
      efficient response in the provision of care to patients with a massive and
      uncontrolled hemorrhage. The purpose of this article is to discuss a massive
      transfusion protocol and to describe the process used to implement a massive
      transfusion protocol at Winnipeg's Health Sciences Centre (the site) as well as
      to describe its impact in the operating room department.

PMID- 26310037
TI  - LISTEN WHILE YOU WORK? The Attitude of Healthcare Professionals to Music in the
      OR.
AB  - Although the playing of music is commonplace in the operating theatre, there is
      nothing in the literature examining whether staff feel this is beneficial.
      Questionnaires were distributed amongst a random selection of staff in practice
      at a district general hospital: medical staff from a range of surgical
      specialities, anaesthetists, and all grades of perioperative staff
      (nurse/operating department practitioners/healthcare assistants) were encouraged
      to participate. There were 121 health professionals in total working in the
      operating theatres. The authors compared the responses to each question amongst
      the respondents, to check for the tendency to correlate. Out of the 52 health
      professionals who responded, 36 stated that music is played in their theatre
      either every day, or two to three times a week. Only five respondents felt that
      this was too often. Fifteen percent of medical staff were of the opinion that the
      nursing staff controlled the choice of music. Nursing staff were almost evenly
      split in thinking that nursing staff, surgical staff and the whole theatre team
      controlled the choice of music. The majority of both nursing and medical staff
      felt that they enjoyed their work more and performed better when music was played
      in theatre. The study concluded that the majority of theatre staff found
      listening to music while they work a positive experience. The potential for music
      to have a distracting or detrimental effect on a minority of individuals should
      always be considered.

PMID- 26310038
TI  - Hypersensitivity Pneumonitis: A Comprehensive Review.
AB  - Hypersensitivity pneumonitis (HP), also known as extrinsic allergic alveolitis,
      is a complex pulmonary syndrome mediated by the immune system and caused by
      inhalation of a wide variety of antigens to which the individual has been
      previously sensitized. The pathobiology of the disease is not fully understood,
      but in addition to the triggers that initiate the disease, host/genetic factors
      are likely to be important, as only a minority of exposed individuals develop HP.
      Due to the lack of a diagnostic gold standard, the diagnosis of HP is not
      straightforward and relies on the integration of a number of factors, including
      history of exposure, precipitating antibodies to the offending antigen, clinical
      features, bronchoalveolar lavage, and radiological and pathologic features.
      However, in the appropriate setting, a high index of suspicion is critically
      important and may obviate the need for more invasive tests. Clinical presentation
      and natural history vary widely. Acute forms generally resolve without sequelae,
      while chronic forms, which are caused by persistent low-grade exposures, are
      associated with poor prognosis. Corticosteroids may be useful in acute episodes
      for symptomatic relief or in chronic and progressive disease, but their long-term
      efficacy has never been validated in prospective clinical trials. Ideally,
      patients with HP should be referred to centers with expertise, as the overlap
      with other forms of interstitial lung disease may be substantial. Making the
      correct diagnosis has critical therapeutic and prognostic implications.

PMID- 26310039
TI  - Immune Polarization in Allergic Patients: Role of the Innate Immune System.
AB  - Allergens come into contact with the immune system as components of a very
      diverse mixture. The most common sources are pollen grains, food, and waste.
      These sources contain a variety of immunomodulatory components that play a key
      role in the induction of allergic sensitization. The way allergen molecules bind
      to the cells of the immune system can determine the immune response. In order to
      better understand how allergic sensitization is triggered, we review the
      molecular mechanisms involved in the development of allergy and the role of
      immunomodulators in allergen recognition by innate cells.

PMID- 26310040
TI  - Hypersensitivity to Nonsteroidal Anti-inflammatory Drugs in Children and
      Adolescents: Cross-Intolerance Reactions.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are used worldwide and are
      responsible for several types of drug hypersensitivity reactions (DHRs) in all
      age groups. The 2 major groups of DHRs to NSAIDs are those induced by
      immunological mechanisms (selective reactions) and those where inflammatory
      mediators are released through activation of the prostaglandin-leukotriene
      pathway without specific immunological recognition (cross-intolerance). In the
      present review, we focus on cross-intolerance reactions, which are the most
      frequent DHRs and are becoming a topic of major interest in children and
      adolescents. Paracetamol and ibuprofen are the drugs that most frequently cause
      DHRs in children; other NSAIDs are responsible for reactions in adolescents. In
      vivo and in vitro tests are of limited diagnostic value, with some exceptions for
      the less common selective reactions. In cross-intolerance, the clinical history
      and controlled administration are in many instances the only way to establish a
      diagnosis and look for alternatives. The clinical history is diagnostic when
      consistent symptoms occur repeatedly after exposure to NSAIDs with different
      chemical structures. Cutaneous and respiratory symptoms often co-occur in young
      children. The natural history of these reactions in children is unknown, and some
      patients can develop tolerance over time. Atopy remains a major risk factor for
      cross-intolerant reactions. The increasing interest in hypersensitivity to NSAIDs
      with improvements in patient phenotyping and the information provided by
      pharmacogenetics will improve our understanding and management of these reactions
      in the near future.

PMID- 26310041
TI  - Validation of the Spanish Version of the Food Allergy Quality of Life
      Questionnaire-Adult Form (S-FAQLQ-AF).
AB  - INTRODUCTION: Specific food allergy quality of life questionnaires have been
      developed within the context of the EuroPrevall project. We aimed to adapt and
      validate the Food Allergy Quality of Life Questionnaire-Adult Form (FAQLQ-AF) in
      the Spanish language. METHODS: The original English questionnaire was translated
      and culturally adapted into Spanish following World Health Organization
      guidelines. The final Spanish version of the FAQLQ-AF (S-FAQLQ-AF) was approved
      by the original authors. Consecutive patients ( 18 years old) who fulfilled the
      following criteria were recruited: 1) diagnosis of food allergy defined as
      immediate allergic symptoms and a positive prick test or IgE against the culprit
      food(s) and 2) physician-assessed ability to complete the questionnaires.
      Patients completed the S-FAQLQ-AF and a Spanish version of the SF-12
      questionnaire. Reliability was assessed 10 to 14 days after completion of the
      first questionnaire. RESULTS: Eighty-two consecutive outpatients were recruited
      and cross-sectional validity was.assessed based on the correlation between the S
      FAQLQ-AF and the Food Allergy Independent Measure (FAIM) in this population (rho
      = 0.83, P < .0001). The S-FAQLQ-AF showed excellent internal consistency
      (Cronbach alpha, 0.95). S-FAQLQ-AF domains also had excellent internal
      consistency: alpha = 0.93 for allergen avoidance-dietary restrictions; alpha =
      0.83 for emotional impact; alpha = 0.85 for risk of accidental exposure, and
      alpha = 0.66 for food allergy related health. Limited correlation was found
      between the S-FAQLQ-AF and the SF-12. CONCLUSION: The S-FAQLQ-AF is a valid,
      short, easy-to-use, and reliable instrument that discriminates between patients
      with different atopic phenotypes and is suitable for assessing the impact of IgE
      mediated food allergy on patient quality of life.

PMID- 26310042
TI  - Clinical Management and Use of Health Care Resources in the Treatment of Nasal
      Polyposis in Spanish Allergy Centers: The POLAR Study.
AB  - BACKGROUND: Nasal polyposis (NP) is a chronic inflammatory disease that
      constitutes a major health problem with significant comorbidities and a
      considerable associated socioeconomic burden. OBJECTIVE: To describe the clinical
      features and management of patients with NP attending Spanish allergy centers,
      the use of health care resources, and the degree of compliance with the
      diagnostic and therapeutic recommendations of the European Position Paper on
      Rhinosinusitis and Nasal Polyps (EPOS). METHODS: We performed a multicenter,
      observational, and cross-sectional epidemiologic study of 671 patients consulting
      for NP in 67 Spanish allergy departments. We used sociodemographic and clinical
      questionnaires to evaluate clinical characteristics, use of health care
      resources, diagnostic methods, and treatment administered. RESULTS: NP was
      closely associated with asthma (66%), allergic rhinitis (45.9%), and
      hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) (26%). Atopy
      was present in the 50% of cases, with Dermatophagoides pteronyssinus as the most
      frequent sensitizing allergen. Eleven percent of NP patients visited the
      emergency department during the previous year, and more than 58% used primary
      care, allergy, or otorhinolaryngology services. The most frequently used
      diagnostic tests were skin prick tests (93.6%) and anterior rhinoscopy (79.4%).
      Intranasal corticosteroids were the drug class most frequently prescribed by
      allergists (74.6%). Specific immunotherapy was prescribed in 21% of patients.
      CONCLUSIONS: NP is a chronic inflammatory disease that generates considerable use
      of health care resources. The close association with atopy, asthma, and NSAID
      hypersensitivity highlights the usefulness of an allergy workup in all patients
      with NP. Analysis of the clinical management of NP by allergists in Spain
      revealed a high degree of compliance with EPOS diagnostic and therapeutic
      recommendations.

PMID- 26310043
TI  - Do Skin Prick Test and In Vitro Techniques Diagnose Sensitization to Peach Lipid
      Transfer Protein and Profilin Equally Well in Allergy to Plant Food and Pollen?
AB  - OBJECTIVE: To compare the skin prick test (SPT) with in vitro techniques (single
      and multiplex fluorescence enzyme-immunoassay [FEIA]) for detecting sensitization
      to profilin and lipid transfer protein (LTP). METHODS: We retrospectively studied
      181 patients with pollen and/or plant food allergy and 61 controls. SPT was
      performed with date palm profilin (Pho d 2) and peach LTP (Pru p 3), and specific
      IgE (sIgE) to Phl p 12 and Pru p 3 was analyzed using single FEIA and microarray.
      RESULTS: Fifteen of 201 patients with negative results for LTP in the SPT were
      sensitized to this allergen in the in vitro tests, and 18 of 41 patients with
      positive results for LTP in the SPT were not sensitized according to the in vitro
      tests. Seventeen of 186 patients with negative results for profilin in the SPT
      were sensitized to Phl p 12 by serum sIgE, and 30 out of 56 patients with
      positive results for profilin in SPT were not sensitized to Phl p 12 according to
      the other tests. Moderate agreement was observed between the 3 techniques
      studied. CONCLUSIONS: SPT is a sensitive technique for detecting sensitization to
      LTP and profilin. Its results are similar to those of in vitro techniques,
      especially in patients with negative SPT results for peach LTP and palm tree
      profilin.

PMID- 26310044
TI  - Anaphylaxis in Adolescent/Adult Patients Treated in the Emergency Department:
      Differences Between Initial Impressions and the Definitive Diagnosis.
AB  - OBJECTIVES: To contrast the initial suspected etiology of anaphylaxis with the
      postworkup diagnosis in patients attended at the emergency department (ED) of a
      tertiary-level hospital in Spain and to investigate the incidence, causes, and
      management of anaphylaxis. METHODS: We performed an observational study of
      patients aged more than 15 years who came to the ED with anaphylaxis between 2009
      and 2010. All clinical records from the ED were reviewed. We recorded data on
      clinical management, the etiology proposed by the attending emergency physician,
      and the cause reported by the patient. The findings were compared with the
      diagnosis reached after the allergy workup. RESULTS: The incidence of anaphylaxis
      was 0.08%. The most common manifestation was skin-mucosal symptoms (98.3%).
      Anaphylaxis was diagnosed in the ED in only 44% of the cases, regardless of
      severity. Only 39.7% received epinephrine, which was administered more frequently
      when the ED physician diagnosed anaphylaxis, regardless of severity. A total of
      60 patients were subsequently seen at the allergy department. The final etiology
      differed from the initial suspicion in the ED in 45% of cases. The frequency of
      anaphylaxis of uncertain origin decreased from 33.3% to 13.3%. After the allergy
      workup, drugs (41.7%) were considered the main cause of anaphylaxis, followed by
      food (25%). CONCLUSIONS: The incidence of anaphylaxis (0.08%) was double that
      estimated in the ED. Anaphylaxis is underdiagnosed. A correct diagnosis
      conditions the administration of epinephrine, regardless of the severity of
      symptoms. The real etiology of anaphylaxis should only be proposed after an
      allergy workup, which is recommended in all cases, as the real cause can differ
      considerably from the initial impression in the ED.

PMID- 26310045
TI  - Allopurinol Desensitization: A Fast or Slow Protocol?

PMID- 26310046
TI  - Recurrent Anaphylaxis Due to Enoxaparin.

PMID- 26310047
TI  - RAD50 Single-Nucleotide Polymorphism in Predominantly Antibody Deficiency.

PMID- 26310048
TI  - Oral Allergy Syndrome Due to Nut Oleosins.

PMID- 26310049
TI  - Treatment of Severe Cold-Induced Urticaria in a Child With Omalizumab.

PMID- 26310050
TI  - Do Asthmatic Patients and Their Physicians Agree on the Presence and Severity of
      Allergic Rhinitis?

PMID- 26310052
TI  - Anaphylaxis to Intravenous Methylprednisolone Hemisuccinate in a Patient With
      Immune Thrombocytopenia.

PMID- 26310051
TI  - Successful Oral Desensitization in a Patient With Hypersensitivity Reaction to
      Crizotinib.

PMID- 26310053
TI  - Rhinitis Due to Larvae Used in Pet Food.

PMID- 26310054
TI  - Analysis of Mutations in the IL2RG Gene in 2 Asian Infants With X-linked Severe
      Combined Immunodeficiency.

PMID- 26310055
TI  - Get ready: Bundled payments are in your future.
AB  - The Centers for Medicare & Medicaid Services' (CMS') mandatory bundled payment
      pilot project makes clear that the agency intends to reform Medicare
      reimbursement. Hospitals in 75 geographic areas are required to participate in a
      five-year pilot project that puts them at risk for the cost of hip and knee
      replacements from the time of surgery until 90 days after discharge. Already,
      more than 6,500 providers are participating in the Bundled Payments for Care
      Improvement project, a voluntary program where participants can choose from 48
      clinical episodes and four models. Even if they won't be part of a bundled
      payments arrangement, case managers need to shift their thinking to prepare for
      the future of reimbursement by developing close working relationships with post
      acute providers, knowing the services and quality delivered by post-acute
      providers, and being aware of the costs for the entire episode of care. Case
      managers will not be able to handle all the responsibilities necessary in a
      bundled payment arrangement if they have large caseloads.

PMID- 26310056
TI  - New payment models require a shift in thinking.

PMID- 26310057
TI  - Adequate CM staff is vital as reimbursement models change.

PMID- 26310058
TI  - CASE MANAGEMENT INSIDER. The Top 10 Mistakes You May Be Making In Your Case
      Management Department! Part 3.
AB  - This month, we reviewed three additional mistakes that are commonly being made in
      case management departments in hospitals today. Next month, we will review the
      final three of the top mistakes that you may be making in your department.

PMID- 26310059
TI  - Bundled payment initiative means eliminating silos, standardizing care.

PMID- 26310060
TI  - CMS proposes to OK one-midnight inpatient stays.
AB  - The Centers for Medicare & Medicaid Services (CMS) has proposed that stays
      shorter than two midnights be reimbursed as inpatient stays if the documentation
      in the medical record supports it. CMS made the proposal in the Outpatient
      Prospective Payment System proposed rule for 2016 and left the policy unchanged
      for stays of two midnights or longer. CMS also announced that the two Beneficiary
      and Family Centered Care Quality Improvement Organizations (QIOs), Livanta and
      KEPRO, will take over the responsibility of Probe and Educate and will review
      cases for medical necessity when patient stays are one midnight or less,
      referring hospitals with high denial rates to the Recovery Auditors. Case
      managers should continue to assist physicians in determining patient status and
      to make sure that the documentation is complete, accurate, and specifies the
      severity of illness.

PMID- 26310061
TI  - TJC, medical societies warn of EHR safety issues.

PMID- 26310063
TI  - Active Targeting of Nano-Photosensitizer Delivery Systems for Photodynamic
      Therapy of Cancer Stem Cells.
AB  - Cancer stem cells are believed to be the basis for tumor initiation, development,
      metastasis and recurrence; are resistant to most traditional therapies (e.g.,
      chemotherapy and radiotherapy); and have the ability to self-renew, proliferate
      and differentiate. Photodynamic therapy may be a promising novel treatment for
      drug-resistant cancer stem cells because of the selectivity of the
      photosensitizer. One of the most important issues to overcome in photodynamic
      therapy is the photosensitizer-targeted delivery to tumor cells, especially
      cancer stem cells. Nano-photosensitizers comprising molecular photosensitizers
      and water-dispersible nanocarriers with or without moieties possessing the
      ability for specific binding to cancer cells or cancer stem cells are a promising
      strategy for active targeted photosensitizer delivery and photodynamic therapy
      targeted therapy of tumors. In this review, we highlight current and future
      prospects for potential strategies based on nanoscience and nanotechnology for
      nano-photosensitizer-targeted delivery in the photodynamic therapy treatment of
      cancer cells, especially cancer stem cells.

PMID- 26310064
TI  - Biodegradable Particulate Carrier Formulation and Tuning for Targeted Drug
      Delivery.
AB  - Biodegradable micro- and nanoparticles have the potential to reform the drug
      development landscape by improving drug solubility, changing undesirable
      pharmacokinetics, realizing the benefits of new molecules arising from genomic
      and proteomic research, and increasing drug localization in target organs and
      tissues; i.e., drug targeting. This review provides an overview of the in vivo
      fate of biodegradable particulate carriers following administration via several
      routes, as well as how the patient's health state, disease pathophysiology and
      particle physicochemical properties affect such fates. It also discusses some of
      the widely used biodegradable polymers, their in vivo biochemical degradation,
      methods of nanoparticle formulation from such polymers and finally, how such
      methods could be tailored to achieve targeted delivery to specified tissues both
      passively and actively.

PMID- 26310065
TI  - Combined Delivery and Anti-Cancer Activity of Paclitaxel and Curcumin Using
      Polymeric Micelles.
AB  - Paclitaxel (PTX) is efficacious in treating various solid tumors. However, the
      severe adverse effects of its present formulation (Cremophor EL and ethanol) and
      the development of drug resistance by the activation of nuclear factor-kappaB (NF
      kappaB) reduce the anti-tumor activities of PTX. Curcumin (Cur) demonstrates anti
      tumor activity by means of antiangiogenesis and induction of apoptosis as well as
      suppression of the activity of NF-kappaB. Therefore, to improve its antitumor
      activity and eliminate the toxicity of the commercial formulation of PTX, we
      prepared biodegradable monomethoxy poly(ethyleneglycol)-poly(epsilon
      caprolactone) (MPEG-PCL) micelles to co-deliver PTX and Cur using a solid
      dispersion method. The mixed PTX and Cur polymeric micelles (PTX-Cur-M) produced
      were monomorphous micelles of 38 nm in diameter that released PTX and Cur for an
      extended period of time and induced cell apoptosis in vitro. In addition, the PTX
      Cur-M exhibited anti-angiogenic activity in vitro and in vivo. Furthermore, the
      therapeutic efficacy of PTX-Cur-M in a mouse model of colon cancer was evaluated.
      PTX-Cur-M micelles produced significantly more inhibition of tumor growth than
      Cur micelles (Cur-M) and PTX micelles (PTX-M) alone at the same dose (P < 0.05
      and P < 0.05, respectively). Immunohistochemical and immunofluorescent analyses
      demonstrated that PTX-Cur-M enhanced tumor cell apoptosis and inhibited
      angiogenesis to a greater extent than control treatment. Our data suggested that
      PTX-Cur-M may have potential clinical applications in cancer therapy.

PMID- 26310066
TI  - A Novel, Single Step, Highly Sensitive In-Vitro Cell-Based Metabolic Assay Using
      Honeycomb Microporous Polymer Membranes.
AB  - This study describes a novel, simple and versatile system for cell-based assays
      at the bench-top. The system consists of Polyurethane (PU) based honeycomb
      membrane with the active compounds/assay reagents dispensed on its pore linings.
      Membranes with functionalized pores were thus created and used for conducting
      cell based assays. As proof-of-concept Flourocein acetate (FDA) and Propidium
      iodide (PI) were embedded on the pore linings and live/dead assays were performed
      on L929 and Hacat cell lines. The results proved the sensitivity of the membrane
      based cell assay. To ensure the capacity of this system for high throughput
      applications, membrane based live/dead assay was performed on L929 cells with
      varying levels of viability. The results from this experiment were quantified by
      microscopic and spectrofluourimetric techniques both of which were found to
      correlate well. It was concluded that this simple membrane based cell assay is
      highly versatile and enables multiple compounds to be tested on the same
      cell/tissue. Furthermore, this method requires low volumes of assay reagents and
      eliminates many of the wet techniques that are involved in a conventional assay,
      without compromising on the sensitivity. It is anticipated that this
      functionalized membrane system could be easily adapted for both manual and
      automated high content screening experiments including in vitro biomaterial
      evaluation as well as cytotoxicity of nanomaterials.

PMID- 26310067
TI  - Indocyanine Green Derivative Covalently Conjugated with Gold Nanorods for
      Multimodal Phototherapy of Fibrosarcoma Cells.
AB  - A hydrophilic indocyanine green derivative (ICG-Der-02) was covalently doped into
      mesoporous silica-coated gold nanorods (AuNRs/mSiO2). The self-synthesized
      derivative offers one carboxyl functional group on a side chain, which enables
      ICG-Der-02 to be covalently linked to nanomaterials and reduces the probability
      of leakage/desorption of the dye. The detection of infrared luminescence around
      1270 nm confirmed that 102 is efficiently generated by the nanocomposite
      (AuNRs/mSiO2-ICG-Der-02). Furthermore, a second layer of silica was coated onto
      the nanocomposite, which then was conjugated with the alpha(v) integrin-targeting
      cyclic peptide (RGD-4C). The cell tests showed that the resulting nanoconjugate
      (AuNRs/mSiO2-ICG-Der-02/RGD-4C) was able to bind preferentially to HT-1080 human
      fibrosarcoma cells. Due to the synergistic effect of the produced nanoconjugates,
      a dual-modality photothermal and photochemical therapy was successfully achieved
      by 808 nm irradiation. Compared to using photothermal or photochemical therapy
      alone, the dual-modality photothermal/photochemical therapeutic strategy proved
      to be more damaging to HT-1080 cells and enhanced the effectiveness of
      photodestruction. Our work presents a novel approach to the multimodal treatment
      of fibrosarcoma and shows promise for future use in cancer theranostics.

PMID- 26310068
TI  - Theranostic Polymeric Micelles for the Diagnosis and Treatment of Hepatocellular
      Carcinoma.
AB  - Theranostics, which combine molecular imaging (diagnostics) and drug delivery
      (therapeutics) in a single platform, have recently shown great potential in
      cancer therapy. In this article, a polymeric micelle was designed and prepared
      for simultaneous magnetic resonance imaging (MRI) and treatment of hepatocellular
      carcinoma (HCC). Theranostic micelles were assembled using Poly(lactic acid)
      poly(ethylene glycol)-poly(L-lysine)-diethylenetriamine pentaacetic acid (PLA-PEG
      PLL-DTPA) and PLA-PEG-PLL-Biotin. The HCC therapeutic paclitaxel (PTX) was
      encapsulated in the cores and Gd ions for imaging were chelated to the DTPA
      moieties. Biotinylated alpha-fetoprotein (AFP) antibodies were linked to the
      micelle surface by a biotin-avidin reaction to form targeted Gd/PTX-loaded
      micelles (TGPM). TGPM were of spherical or ellipsoidal shape with uniform
      particle size distribution (147.50 +/- 4.71 nm), positive zeta potential (24.45
      +/- 1.04 mV), and high encapsulation efficiency (88.76 +/- 1.64%) and drug
      loading (1.59 +/- 0.06%). The cytotoxicity of TGPM in HepG2 cells was superior to
      that of Taxol or Gd/PTX-loaded micelles (GPM). In MRI tests in vitro, the T1
      relaxivity of TGPM was 21.589 mM(-1) s(-1), 4.4 times higher than Magnevist (r1 =
      4.8 mM(-1) s(-1)). In H22 tumor-bearing mice, TGPM significantly increased tumor
      imaging intensity (more than 3 times) and prolonged imaging time (from 1 to 6 h)
      compared to Magnevist. In vivo, TGPM exhibited higher anti-tumor efficiency than
      Taxol and GPM. These results indicate that TGPM has great potential in HCC
      theranostics.

PMID- 26310069
TI  - Ultrafast Laser Synthesized Nanostructures for Controlling Cell Proliferation.
AB  - The state-of-the-art in synthesis of nanostructured cell and contra-cell surfaces
      relies on techniques that utilize elaborate precursor chemicals, catalysts, or
      vacuum conditions, and any combination thereof. Two type s of nanostructures,
      sodium oxide (Na2O) nanotips and silicon oxide (SiO2) nanofibers, have been
      fabricated on soda-lime glass using ultrafast laser ablation. Control over
      nanotip width was demonstrated via laser dwell time and a new tip formation
      mechanism is proposed. The nanofibers generated in this work display a level of
      nanomorphology unseen in other fiber fabrication methods. The resulting fibers
      show striking morphological similarity to proteins that comprise the natural
      extra cellular matrix. The interaction of both nanostructures with NIH 3T3
      fibroblasts was explored by incubating nanostructured glass with fibroblasts over
      periods of 12 hours, 1 day, or 1 week. The Na2O nanotip surfaces dissolved within
      a day yet appeared to induce apoptosis in cells while the SiO2 nanofibers
      degraded over time but influenced cells to display unique, healthy
      characteristics such as preferential adhesion to nanofibers and increased
      microvilli generation. These growth-positive and growth-negative surfaces for
      cells could find use in novel biological testing equipment.

PMID- 26310070
TI  - The Effect of Intracellular Degradation on Cytotoxicity and Cell Labeling
      Efficacy of Inorganic Ligand-Stabilized Colloidal CdSe/CdS Quantum Dots.
AB  - Quantum dots (QDots) are explored in biomedicine as highly fluorescent,
      photostable nanomaterials, but their use is impeded by their hydrophobic nature.
      In the present work, we evaluate the potential biomedical use of QDots that have
      been transferred into the aqueous phase by means of inorganic ligands. CdSe/CdS
      QDots were prepared and transferred to water upon ligand exchange to S(2-) ions.
      However, a multiparametric evaluation of the effect of these QDots on multiple
      cell types revealed significant QDot cytotoxicity. Using optimized methods, the
      QDots were found to rapidly degrade under endosomal pH, resulting in leached
      Cd(2+). Together with the induction of oxidative stress, this significantly
      affected cell viability. Using proliferation-restricted cells, QDot degradation
      was found to augment cytotoxicity with time resulting in mitochondrial and DNA
      damage, effects on cell morphology and cell functionality. The final non
      cytotoxic concentration was defined at 2 nM, enabling cells to be tracked up to 2
      cell divisions. A direct comparison with other QDots and fluorescent particles
      studied resulted in similar concentrations; however, the functionality of
      previously analyzed particles was much higher. These data reveal that comparing
      NP toxicity based on particle concentrations is extremely difficult. A comparison
      of NPs is better obtained by evaluating NP functionality using a straightforward
      approach, such as follow-up of QDot fluorescence in dividing cells. These data
      highlight the importance of (1) considering QDot stability in the intracellular
      microenvironment, (2) the protective nature of the QDot-stabilizing coating, (3)
      the need for comparison of particle functionality to understand any observed
      effects.

PMID- 26310071
TI  - Nanovector for Gene Transfection and MR Imaging of Mesenchymal Stem Cells.
AB  - This study centers on the use of superparamagnetic iron oxide nanoparticles
      coated with polyethylene glycol-grafted polyethylenimine (PEG-g-PEI-SPION) as an
      MRI-visible and efficient nanovector for the gene modification and in vivo MRI
      tracking of rat bone marrow-derived mesenchymal stem cells (rBMSCs). PEG-g-PEI
      SPION was first condensed with plasmid DNA to form nanoparticles, demonstrating
      low cytotoxicity and good biocompatibility for rBMSCs. Based on a reporter gene
      assay, PEG-g-PEI-SPION/pDNA had the highest transfection efficiency (62.6 +/-
      5.5%) in rBMSCs, which was significantly higher than that obtained using the
      cationic liposomes in lipofectamine 2000, a commercially available and worldwide
      used gene transfection agent, under the most optimal conditions (13.9 +/- 2.6%; P
      < 0.05). More excitingly, the transplantation of rBMSCs modified by our MRI
      visible vector complexed with a plasmid encoding human hepatocyte growth factor
      into fibrotic rat livers effectively restored albumin production and
      significantly suppressed transaminase activities. In addition, the transplanted
      rBMSCs displayed a sensitive signal on T2/T2*-weighted images in vitro and in
      vivo, which enabled effective MRI tracking of the cells for up to 14 days post
      transplantation. Although mesenchymal stem cells are well-known to be refractory
      in most of the current nonviral gene delivery techniques, our results demonstrate
      that the MRI-sensitive PEG-g-PEI-SPION is a highly efficient and readily
      observable nanovector for gene delivery into rBMSCs.

PMID- 26310072
TI  - Chitosan-Fibrin Nanocomposites as Drug Delivering and Wound Healing Materials.
AB  - In the present study, chitosan-fibrin nanocomposites (CFNs) were prepared using a
      novel method and analysed for their physico-chemical properties. TEM and SEM
      studies revealed their size in the range of 24-28 nm with zeta potential value of
      + 16 mV. Anti-bacterial activity of CFN was investigated against Escherichia coli
      and Staphylococcus aureus. For drug delivery applications, 71% of methotrexate
      (MTX) was entrapped in CFNs that displayed sustained release for up to 96 h. Anti
      cancer activity of MTX-CFN was evaluated on HeLa and MCF 7 cells, which showed
      dose-dependent toxicity on both the cell lines. Further, the role of CFN in wound
      healing was studied by creating open excision wounds on albino rats. Topical
      application of CFN, once in two days, for up to 10 days resulted in complete
      healing of wounds on day 14 whereas it took 22 days in control. Histological and
      biochemical analyses proved increased synthesis of collagen with active migration
      of fibroblasts and epithelial cells in CFN treated wounds. From our study, it is
      proposed that CFN may be used as a suitable candidate for drug delivery and wound
      healing applications.

PMID- 26310073
TI  - Biodegradable Multiamine Polymeric Vector for siRNA Delivery.
AB  - The gene silencing activity of small interfering RNA (siRNA) has led to their use
      as tools for target validation and as potential therapeutics for a variety of
      diseases. A major challenge is the development of vectors with high delivery
      efficiency and low toxicity. Although poly(ethylenimine) (PEI) has been regarded
      as the most promising polymeric vector for nucleic acid delivery, the
      nonbiodegradable structure greatly hinders its clinical application. In the
      present study, a diblock copolymer, PEG-PAsp(DIP-DETA), of poly(ethylene glycol)
      (PEG) and poly(L-aspartic acid) (PAsp) randomly grafted with pH-sensitive 2
      (diisopropylamino)ethylamine (DIP) and diethylenetriamine (DETA) groups was
      synthesized via ring-opening polymerization and aminolysis reaction. Similar to
      polyethylenimine (PEI), the copolymer possesses a multiamine structure that not
      only allows effective siRNA complexation at neutral pH but also facilitates
      lysosomal release of siRNA via a proton buffering effect. Moreover, the poly(L
      aspartic acid) backbone renders the vector biodegradability, which is not
      achievable with PEI. This novel polymeric vector can mediate effective
      intracellular siRNA delivery in various cancer cells. Consequently, the delivery
      of BCL-2 siRNA resulted in target gene silencing, inducing apoptosis and
      inhibiting the growth of cancer cells. These results show the potential of this
      non-PEI based polymeric vector with proton buffering capacity and
      biodegradability for siRNA delivery in cancer therapy.

PMID- 26310074
TI  - beta-Cyclodextrin-Linked Polyethylenimine Nanoparticles Facilitate Gene Transfer
      and Enhance the Angiogenic Capacity of Mesenchymal Stem Cells for Wound Repair
      and Regeneration.
AB  - Repair of deep wounds by cell transplantation strongly depends on angiogenesis
      and on the regeneration of skin and appendages. In this study, plasmid DNA
      encoding vascular endothelial growth factor-165 (VEGF-165) was transduced into
      bone-marrow mesenchymal stem cells (MSCs) using a nonviral vector, beta
      cyclodextrin-linked polyethylenimine, to enhance angiogenic capacity. The effects
      of MSCs administered by intradermal injection or transplantation on wound closure
      were compared in a full-thickness excision wound model. The results showed that
      the MSC-seeded sponge had significantly stronger acceleration in wound closure
      than the MSC injection. The effects on wound repair and regeneration of
      transplanted MSCs and pDNA-VEGF1 65-transfected MSCs (TMSCs) with gelatin/beta
      tricalcium phosphate scaffold were also investigated. Compared with MSC
      transplantation, TMSC transplantation showed higher efficacy in stimulating wound
      closure, promoting dermal collagen synthesis and regulating the deposition of
      newly formed collagen. In addition, the angiogenic capacity of the TMSCs was
      higher than that of the MSCs. The results indicate that the nonviral genetic
      engineering of the MSCs is a promising strategy to enhance the angiogenic
      capacity of MSCs for wound repair and angiogenesis. Functional gene-activated
      MSCs may be used as cost-effective and accessible seed cells for skin tissue
      engineering and as novel carriers for wound gene therapy.

PMID- 26310075
TI  - Lipid Nanosystems Enhance the Bioavailability and the Therapeutic Efficacy of
      FTY720 in Acute Myeloid Leukemia.
AB  - Protein phosphatase 2A (PP2A) is a serin-threonin phosphatase that regulates many
      proteins critical for malignant cell behavior; therefore, PP2A is considered to
      be a human tumor suppressor. In this study, we assessed the pharmacokinetic
      profile and the antileukemic effects of the PP2A activator FTY720, free or
      encapsulated in lipid nanoparticles, in in vitro and in vivo models of acute
      myeloid leukemia. FTY720 lipid nanoparticles presented diameters around 210 nm,
      with an encapsulation efficiency up to 75% and significantly increased FTY720
      oral bioavailability. In addition, FTY720 restores PP2A phosphatase activity and
      decreases phosphorylation of PP2A and its targets Akt, ERK1/2 and STAT5, all
      implicated in the pathogenesis of acute myeloid leukemia. Moreover, FTY720 exerts
      an additive anti-leukemic effect in combination with drugs used in standard
      induction therapy. Importantly, FTY720 lipid nanoparticles were more efficient at
      inducing cell growth arrest and apoptosis than FTY720 solution. Finally, oral
      administration of FTY720 lipid nanoparticles to mice every three days was as
      effective in reducing acute myeloid leukemia xenograft tumor growth as daily oral
      administration of FTY720. These results provide the first evidence for the
      potential use of FTY720 lipid nanoparticles as an oral therapeutic agent in acute
      myeloid leukemia.

PMID- 26310076
TI  - An Electrochemical Genosensing Assay Based on Magnetic Beads and Gold
      Nanoparticle-Loaded Latex Microspheres for Vibrio cholerae Detection.
AB  - An ultrasensitive electrochemical genosensing assay was developed for the
      sequence-specific detection of Vibrio cholerae DNA using magnetic beads as the
      biorecognition surface and gold nanoparticle-loaded latex microspheres (latex
      AuNPs) as a signal-amplified hybridization tag. This biorecognition surface was
      prepared by immobilizing specific biotinylated capturing probes onto the
      streptavidin-coupled magnetic beads. Fabricating a hybridization tag capable of
      amplifying the electrochemical signal involved loading multiple AuNPs onto
      polyelectrolyte multilayer film-coated poly(styrene-co-acrylic acid) latex
      microspheres as carrier particles. The detection targets, single-stranded 224-bp
      asymmetric PCR amplicons of the V. cholerae lolB gene, were sandwich-hybridized
      to magnetic bead-functionalized capturing probes and fluorescein-labeled
      detection probes and tagged with latex-AuNPs. The subsequent electrochemical
      stripping analysis of chemically dissolved AuNPs loaded onto the latex
      microspheres allowed for the quantification of the target amplicons. The high
      loading capacity of the AuNPs on the latex microspheres for sandwich-type dual
      hybridization genosensing provided eminent signal amplification. The genosensing
      variables were optimized, and the assay specificity was demonstrated. The
      clinical applicability of the assay was evaluated using spiked stool specimens.
      The current signal responded linearly to the different V. cholerae concentrations
      spiked into stool specimens with a detection limit of 2 colony-forming units
      (CFU)/ml. The proposed latex-AuNP-based magnetogenosensing platform is promising,
      exhibits an effective amplification performance, and offers new opportunities for
      the ultrasensitive detection of other microbial pathogens.

PMID- 26310077
TI  - High Drug Payload 10-Hydroxycamptothecin Nanosuspensions Stabilized by
      Cholesterol-PEG: In Vitro and In Vivo Investigation.
AB  - The objective of this study was to evaluate the feasibility of producing 10
      hydroxycamptothecin nanosuspensions with high drug payload and to then determine
      the in vitro and in vivo characteristics of these nanosuspensions. Using
      cholesterol-PEG600 as a stabilizer, 10-hydroxycamptothecin nanosuspensions were
      successfully prepared using a precipitation-combined high-pressure homogenization
      method. A satisfactory drug payload of 90.39% (w/w) was achieved. The obtained
      nanosuspensions were spherical, with a mean particle size of 115.0 +/- 0.4 nm,
      and they were monodisperse with a polydispersity index of 0.134 +/- 0.001. The 10
      hydroxycamptothecin remained in the same crystalline form in both the
      nanosuspensions and the bulk powder. In vitro, the 10-hydroxycamptothecin
      nanosuspensions released the encapsulated drug with nearly zero-order kinetics,
      and the accumulative release reached 90% within 72 hours. In vitro cytotoxicity
      assay showed that the 1 0-hydroxycamptothecin nanosuspensions had significantly
      enhanced cytotoxicity against HepG2 cells compared to the commercially available
      10-hydroxycamptothecin injections. The in vivo study with H22 tumor-bearing mice
      and intravenous injection of the drug showed that in contrast to the 10
      hydroxycamptothecin injections, the 10-hydroxycamptothecin nanosuspensions
      exhibited significantly enhanced biodistribution, particularly in the lung
      (393.40-fold AUC(0-24h)), liver (192.35-fold AUC(0-24h)), spleen (141.67-fold
      AUC(0-24h)) and tumor (64.21-fold AUC(0-24h)). The 10-hydroxycamptothecin
      nanosuspensions also showed improved antitumor therapeutic efficacy over the
      injections (89.83% vs. 30.56%). This suggests that cholesterol-PEG600 may be an
      effective stabilizer for the preparation of hydrophobic drug nanosuspensions and
      that 10-hydroxycamptothecin nanosuspensions are a promising drug delivery system
      for tumor treatment.

PMID- 26310078
TI  - Unique Biological Degradation Behavior of Stober Mesoporous Silica Nanoparticles
      from Their Interiors to Their Exteriors.
AB  - The degradation behavior of mesoporous silica nanoparticles (MSNs) influences
      their biological applications. The present study was a systematic investigation
      of the biological degradation behavior of mesoporous silica synthesized by the
      Stober method. Different sized Stober mesoporous silica nanoparticles were
      prepared and immersed in simulated body fluid, and degradation curves were
      obtained by measuring the dissolved silicon content of the fluid. Structural
      changes during degradation were observed by transmission electron microscope
      (TEM). The Stober mesoporous silica nanoparticles tended to become hollow during
      the degradation process, and each particle was almost completely degradable from
      its interior to its exterior. Because of this unique degradation behavior, the
      morphology of the Stober mesoporous silica nanoparticles can be retained even
      after over 85% of the silica degraded. Thus, during degradation, the
      dispersibility of the silica particles was superior to that of MSNs prepared in
      aqueous phases. Furthermore, the degradation behavior, intracellular
      distribution, and structural transformation of Stober mesoporous silica
      nanoparticles in human embryo kidney 293T cells were investigated by measuring
      the silicon content in culture medium and analyzing TEM images. When these silica
      nanoparticles degraded in cells, their size and dispersibility remained
      unchanged, which would reduce the biological toxicity associated with the
      accumulation of silica aggregates in tissues. Overall, these results demonstrate
      that Stober mesoporous silica nanoparticles can degrade in biological medium from
      inside to outside and maintain their good dispersibility, which suggests that
      these nanoparticles have great potential for applications as degradable
      biomedical materials such as drug carriers.

PMID- 26310079
TI  - Labeling and Tracking of Human Pancreatic Islets Using Carbon Nanotubes.
AB  - Limited tools are available for the non-invasive monitoring of transplanted
      islets. In this study, we have compared the widely used superparamagnetic iron
      oxide nanoparticle ferumoxide (Endorem) and multiwalled carbon nanotubes (MWCNTs)
      for islet cell labeling and tracking. INS-1 E cells and human pancreatic islets
      isolated from 12 non-diabetic cadaveric organ donors (age: 62 +/-16 yr, BMI: 24.6
      +/- 3.3 kg/m2) were incubated with 50 MUg/ml Endorem or 15 MUg/ml MWCNTs and
      studied after 7 or 14 days to assess beta cell morphology, ultrastructure,
      function, cell survival and in-vitro and in-vivo magnetic resonance imaging
      (MRI). Light and electron (EM) microscopy showed the well-maintained morphology
      and ultrastructure of both INS-1 E and human islets during the incubation. EM
      also revealed the presence of Endorem and MWCNTs within the beta but not the
      alpha cells. The compounds did not affect beta cell function and viability, and
      in-vitro MRI showed that labeled INS-1 E cells and human islets could be imaged.
      Finally, MWCNT labeled human islets were successfully transplanted into the
      subcutis of rats localized in the desired site via magnetic field and tracked by
      MRI. These data suggest that MWCNTs can be an alternative labeling compound to be
      used with human islets for experimental and transplantation studies.

PMID- 26310080
TI  - Caring in a chemical generation.

PMID- 26310081
TI  - Drug use v drug abuse.

PMID- 26310082
TI  - Maternity services funding gap.

PMID- 26310084
TI  - Factors that affect breastfeeding duration.

PMID- 26310086
TI  - Substance use in pregnancy.
AB  - The increase in substance use which occurred in the 1980s was disproportionately
      large among women of reproductive age, so both the numbers of women who use drugs
      and the duration of drug use have increased (Hepburn 2004). While drug use occurs
      throughout society, the type and pattern of drug use that is associated with
      medical and social problems is closely associated with socio-economic
      deprivation. Socio-economic deprivation is in turn associated with unhealthy
      lifestyles and behaviours such as smoking and poor diet. Deprivation, associated
      lifestyles and substance use adversely affect the health of mother and baby, so
      the effects are cumulative. Consequently women with problem drug and/or alcohol
      use have potentially complex pregnancies (Hepburn 2004).

PMID- 26310087
TI  - Paranoid or persecuted? The stigmatisation of pregnant drug users: a literature
      review.
AB  - Substance misuse is a complex issue, fraught with many challenges and
      inequalities for those affected; most of these are as a result not of the
      substances themselves, but of the underlying web of socioeconomic problems
      associated. Whilst the literature suggests that pregnancy may be a 'window of
      opportunity' for substance misusing women, it also suggests that there are
      several barriers to women engaging with health care. One of these is the fear of
      being judged and stigmatised by healthcare professionals. This literature review
      looks at research in the field of substance misuse in pregnancy, focusing on the
      'stigmatisation' of pregnant drug users by healthcare professionals, illustrating
      the potential impact of this upon care.

PMID- 26310088
TI  - Cocaine use and the breastfeeding mother.
AB  - Cocaine is the second most commonly used illicit drug. Use in pregnancy and
      breastfeeding may have severe consequences for the baby due to its
      pharmacokinetic properties. Midwives need to be aware of the prolonged action of
      cocaine and be alert to the possibility of cocaine toxicity if a baby is
      excessively irritable and tachycardic. Euphoric highs are brief but breast milk
      and urine remain positive for long periods. Infant urine following exposure to
      cocaine via breast milk may remain positive for up to 60 hours. Mothers who snort
      cocaine should pump and dump breast milk for 24-48 hours. Passive inhalation of
      crack cocaine smoke may also result in infants with positive toxicology screens.
      Cocaine powder should never be applied to the nipples of breastfeeding mothers.

PMID- 26310089
TI  - The rise of remifentanil and the decline of midwifery autonomy.
AB  - Since the 1980s epidural analgesia has been considered the gold standard for pain
      relief in labour. Over the past decade there has been a growing trend in UK
      maternity units to offer remifentanil PCA as a fast, safe alternative for women
      where epidural analgesia is contraindicated. Increasingly more obstetric units
      and anaesthetists are extending the use of remifentanil and in many units it is
      now preferred over central neuroaxial blocks (Stocki et al 2014). It would appear
      that remifentanil is being hailed as the panacea for labour pain. Whilst
      discussion around the use and effects of remifentanil is very well documented in
      anaesthetic journals, there is very little midwifery research around this
      subject. Following a review of the current evidence, this article will explore
      the use of remifentanil in labour, consequences for women and neonates and
      implications for midwifery practice.

PMID- 26310090
TI  - Reaching out: caring for women prisoners in Western Australia.
AB  - Incarcerated women are a vulnerable group with complex needs in pregnancy, birth
      and early parenting; and this is further complicated with a drug and/or alcohol
      addiction. Prior to the establishment of an antenatal outreach clinic in a
      Western Australian prison for women, pregnant inmates received fragmented
      antenatal care. Some of the women did not disclose drug and alcohol issues for
      fear of involvement of child protection services, and some refused to be
      transported for care to maternity hospitals for antenatal appointments. This is
      the first antenatal care clinic for pregnant women to be established within a
      prison population in Western Australia.

PMID- 26310091
TI  - Looking after your health. 2. Avoiding constipation at work.
AB  - This article is to summarise key concepts for the health of the midwife, with
      particular focus on constipation. This is often a taboo subject even amongst
      women whi aren't midwives, so they do not always freely discuss the issue. It is
      a key discussion when talking through iron supplementation, hormonal changes and
      nutrition within the realm of the midwife. Raising awareness and taking care of
      your own bowel habits is key to enjoying future health and wellbeing.

PMID- 26310092
TI  - Synthetic oxytocin: looking beyond the benefits.
AB  - While the notion of drug abuse tends to be applied more to substances used
      outside of medical settings, there is increased concern that synthetic oxytocin
      is being overused in maternity care settings. This article presents an overview
      of some of the issues that have been raised within this area, including the risks
      that have been cited by recent research, social scientists and childbirth
      commentators, the concerns that are being anecdotally discussed by midwives and,
      even more importantly, the experiences of women themselves.

PMID- 26310093
TI  - Midwifery basics: Mentorship. 4. Assessing students.

PMID- 26310094
TI  - 'Midwives' experiences of establishing partnerships: working with pregnant women
      who use illicit drugs.

PMID- 26310095
TI  - Pride in our wonderful NHS.

PMID- 26310096
TI  - The Future of our Profession is n Good Hands .

PMID- 26310097
TI  - 2015 Legislative Session Overview.

PMID- 26310098
TI  - ODA New Dentist Nicole Reynolds, Oklahoma City, OK.

PMID- 26310099
TI  - The State of the State at the OU College of Dentistry.

PMID- 26310100
TI  - Mandibular Gingiva.

PMID- 26310101
TI  - Electronic monitoring of orthopedic brace compliance.
AB  - PURPOSE: Brace compliance measurement in adolescent idiopathic scoliosis (AIS)
      has been the subject of a few recent studies. Various sensors have been developed
      to measure compliance. We have developed a temperature-based data logger-the
      Cricket-specifically for scoliosis braces, with associated custom software, that
      is embedded directly in the brace. The purpose of this study was to analyze
      patterns of brace wear and patient compliance among children with AIS using the
      Cricket. METHODS: Fifty-five AIS patients prescribed various brace-time regimens
      were monitored using the Cricket. All subjects were treated with the Wilmington
      brace. The compliance rate for each group was determined. RESULTS: Overall
      compliance among subjects was 69.9 +/- 31.5 %. Only 14.5 % met or exceeded
      prescribed brace time. This is consistent with previous compliance monitoring
      results. CONCLUSION: The results of this study objectively show the difference
      between prescribed and actual brace wear time and reaffirm the Cricket sensor as
      an accurate and comfortable brace-monitoring device.

PMID- 26310102
TI  - Six-year follow up of silodosin monotherapy for the treatment of lower urinary
      tract symptoms suggestive of benign prostatic hyperplasia: What are the factors
      for continuation or withdrawal?
AB  - OBJECTIVES: To investigate the factors for continuation or withdrawal as an
      extension of a prospective study of silodosin monotherapy for the treatment of
      lower urinary tract symptoms suggestive of benign prostatic hyperplasia for more
      than 6 years. METHODS: A total of 104 patients (age 71.5 +/- 8.2 years) were
      enrolled in the present study. The mean prostate volume was 44.1 +/- 23.9 mL.
      International Prostate Symptom Score, quality of life index, maximum flow rate,
      and postvoid residual urine volume were determined at baseline, and at 1, 3, 6
      and 12-72 months after treatment. RESULTS: Adverse events were noted in 14
      patients (13.5%), and the most frequent adverse event was ejaculatory dysfunction
      (5.8%). Withdrawal was noted in 78 patients, and 26 patients (25.0%) were still
      taking silodosin at 72 months (continuing group). The reasons for withdrawals
      were: unknown in 27 patients (26.0%), adverse events in nine patients (8.7%),
      unsatisfactory effects in 30 patients (28.8%) and satisfied with the current
      condition for six patients (5.8%). In 30 patients who withdrew because of
      unsatisfactory effects, surgery was carried out in 21 patients (surgery group).
      The baseline total International Prostate Symptom Score did not differ between
      the continuing group and the surgery group. However, patients with the continuing
      group had significantly smaller baseline prostate volume, and lower baseline
      quality of life index and prostate-specific antigen, than in the surgery group.
      The mean total International Prostate Symptom Score, quality of life index and
      maximum flow rate improved significantly at 1 month, and remained stable up to 72
      months. CONCLUSIONS: The withdrawal rate was higher in patients with a larger
      prostate. The effects of silodosin for lower urinary tract symptoms was immediate
      and stable up to 72 months.

PMID- 26310103
TI  - Diquafosol sodium ophthalmic solution for the treatment of dry eye: clinical
      evaluation and biochemical analysis of tear composition.
AB  - PURPOSE: To evaluate the clinical efficacy of 3% diquafosol sodium ophthalmic
      solution for dry eye, and to analyze the concentration of tear proteins and mucin
      like substances after the treatment. METHODS: Fifty eyes of 25 patients with dry
      eye syndrome were prospectively enrolled. The patients were treated with
      diquafosol solution at a dose of 1 drop in each eye 6 times daily for 4 weeks.
      The parameters of clinical efficacy were tear osmolarity, tear breakup time
      (BUT), fluorescein staining scores for the cornea and conjunctiva, Schirmer test
      values, and subjective symptoms evaluated using the ocular surface disease index
      (OSDI). Tears collected with Schirmer test strips were analyzed by high
      performance liquid chromatography, and the concentrations of the total protein
      and the 4 major tear proteins, namely, secretory IgA, lactoferrin, lipocalin-1,
      lysozyme, and N-acetyl-neuraminic acid (Neu5Ac), were measured. Neu5Ac is a major
      sialic acid, a marker of secretory mucins. RESULTS: The BUT, keratoconjunctival
      staining scores, and Schirmer test values were improved with statistical
      significance after the treatment with diquafosol solution, while changes in the
      other parameters, including tear osmolarity, corneal staining scores, and OSDI
      scores were not significant. The Neu5Ac concentration was significantly
      increased, which was not accompanied by changes in tear proteins. CONCLUSIONS:
      Topical application of diquafosol significantly improved the clinical parameters
      of the BUT, keratoconjunctival staining scores, and Schirmer test values and was
      accompanied by increased sialic acid content in the tears of patients with dry
      eye.

PMID- 26310104
TI  - Differential coral bleaching-Contrasting the activity and response of enzymatic
      antioxidants in symbiotic partners under thermal stress.
AB  - Mass coral bleaching due to thermal stress represents a major threat to the
      integrity and functioning of coral reefs. Thermal thresholds vary, however,
      between corals, partly as a result of the specific type of endosymbiotic
      dinoflagellate (Symbiodinium sp.) they harbour. The production of reactive oxygen
      species (ROS) in corals under thermal and light stress has been recognised as one
      mechanism that can lead to cellular damage and the loss of their symbiont
      population (Oxidative Theory of Coral Bleaching). Here, we compared the response
      of symbiont and host enzymatic antioxidants in the coral species Acropora
      millepora and Montipora digitata at 28 degrees C and 33 degrees C. A. millepora
      at 33 degrees C showed a decrease in photochemical efficiency of photosystem II
      (PSII) and increase in maximum midday excitation pressure on PSII, with
      subsequent bleaching (declining photosynthetic pigment and symbiont density). M.
      digitata exhibited no bleaching response and photochemical changes in its
      symbionts were minor. The symbiont antioxidant enzymes superoxide dismutase,
      ascorbate peroxidase, and catalase peroxidase showed no significant upregulation
      to elevated temperatures in either coral, while only catalase was significantly
      elevated in both coral hosts at 33 degrees C. Increased host catalase activity in
      the susceptible coral after 5days at 33 degrees C was independent of antioxidant
      responses in the symbiont and preceded significant declines in PSII photochemical
      efficiencies. This finding suggests a potential decoupling of host redox
      mechanisms from symbiont photophysiology and raises questions about the
      importance of symbiont-derived ROS in initiating coral bleaching. 

PMID- 26310105
TI  - Oxidative stress and antioxidant status in a lizard Phrynocephalus vlangalii at
      different altitudes or acclimated to hypoxia.
AB  - Oxidative stress is a major challenge for the survival of animals living on
      plateaus; however, lifelong exposure to high altitudes could generate certain
      adaptabilities which make them more tolerant to these environments. The aim of
      the present study was to compare the oxidative stress and antioxidant status
      between low altitude (LA, 2900m) and high altitude (HA, 4200m) populations of
      Phrynocephalus vlangalii. The results showed that malondialdehyde levels in the
      HA populations decreased significantly in the brain, but markedly increased in
      the muscle and had no significant difference in the liver compared to LA
      populations. The activity of catalase in the brain was much higher in HA than LA.
      Except for total antioxidant capacity and glutathione reductase, other
      antioxidants were similar between the two populations in livers. By contrast, the
      levels of most antioxidants in muscle decreased markedly with elevation. We also
      explored the effects of hypoxia on oxidative damage and antioxidant defenses in
      P. vlangalii. The lizards were acclimated in a simulated hypoxic chamber (15% O2
      and 8% O2) for 6weeks. The results showed that in the 8% O2 group, the levels of
      malondialdehyde, catalase, glutathione and total antioxidant capacity in the
      brain, and malondialdehyde, catalase and superoxide dismutase in the liver were
      significantly higher than the 15% O2 group. These findings indicate that in this
      species the oxidative stress and antioxidant capacity are subject to altitude and
      hypoxia and this lizard may have acquired some ability to deal with the oxidative
      stress. 

PMID- 26310106
TI  - Topographical effects on fiber-mediated microRNA delivery to control
      oligodendroglial precursor cells development.
AB  - Effective remyelination in the central nervous system (CNS) facilitates the
      reversal of disability in patients with demyelinating diseases such as multiple
      sclerosis. Unfortunately until now, effective strategies of controlling
      oligodendrocyte (OL) differentiation and maturation remain limited. It is well
      known that topographical and biochemical signals play crucial roles in modulating
      cell fate commitment. Therefore, in this study, we explored the combined effects
      of scaffold topography and sustained gene silencing on oligodendroglial precursor
      cell (OPC) development. Specifically, microRNAs (miRs) were incorporated onto
      electrospun polycaprolactone (PCL) fiber scaffolds with different fiber diameters
      and orientations. Regardless of fiber diameter and orientation, efficient
      knockdown of differentiation inhibitory factors were achieved by either
      topography alone (up to 70%) or fibers integrated with miR-219 and miR-338 (up to
      80%, p < 0.05). Small fiber promoted OPC differentiation by inducing more RIP(+)
      cells (p < 0.05) while large fiber promoted OL maturation by inducing more MBP(+)
      cells (p < 0.05). Random fiber enhanced more RIP(+) cells than aligned fibers (p
      < 0.05), regardless of fiber diameter. Upon miR-219/miR-338 incorporation, 2 MUm
      aligned fibers supported the most MBP(+) cells (~17%). These findings indicated
      that the coupling of substrate topographic cues with efficient gene silencing by
      sustained microRNA delivery is a promising way for directing OPC maturation in
      neural tissue engineering and controlling remyelination in the CNS. 

PMID- 26310107
TI  - Cost-effective differentiation of hepatocyte-like cells from human pluripotent
      stem cells using small molecules.
AB  - Significant efforts have been invested into the differentiation of stem cells
      into functional hepatocyte-like cells that can be used for cell therapy, disease
      modeling and drug screening. Most of these efforts have been concentrated on the
      use of growth factors to recapitulate developmental signals under in vitro
      conditions. Using small molecules instead of growth factors would provide an
      attractive alternative since small molecules are cell-permeable and cheaper than
      growth factors. We have developed a protocol for the differentiation of human
      embryonic stem cells into hepatocyte-like cells using a predominantly small
      molecule-based approach (SM-Hep). This 3 step differentiation strategy involves
      the use of optimized concentrations of LY294002 and bromo-indirubin-3'-oxime
      (BIO) for the generation of definitive endoderm; sodium butyrate and dimethyl
      sulfoxide (DMSO) for the generation of hepatoblasts and SB431542 for
      differentiation into hepatocyte-like cells. Activin A is the only growth factor
      required in this protocol. Our results showed that SM-Hep were morphologically
      and functionally similar or better compared to the hepatocytes derived from the
      growth-factor induced differentiation (GF-Hep) in terms of expression of hepatic
      markers, urea and albumin production and cytochrome P450 (CYP1A2 and CYP3A4)
      activities. Cell viability assays following treatment with paradigm
      hepatotoxicants Acetaminophen, Chlorpromazine, Diclofenac, Digoxin, Quinidine and
      Troglitazone showed that their sensitivity to these drugs was similar to human
      primary hepatocytes (PHHs). Using SM-Hep would result in 67% and 81% cost
      reduction compared to GF-Hep and PHHs respectively. Therefore, SM-Hep can serve
      as a robust and cost effective replacement for PHHs for drug screening and
      development. 

PMID- 26310108
TI  - Oral delivery of shRNA based on amino acid modified chitosan for improved
      antitumor efficacy.
AB  - In this investigation, chitosan-histidine-cysteine (CHC) was engineered for oral
      delivery of Survivin short hairpin RNA (shRNA)-expressing plasmid DNA (shSur
      pDNA) to promote hepatoma regression through integrating the advantages of
      histidine and cysteine to conquer serial cellular and systemic barriers. CHC
      could effectively encapsulate shSur-pDNA to form compact nanocomplexes (NC) at
      adequate weight ratios. Sequential modification with histidine and cysteine
      conferred CHC NC with the beneficial attributes for shRNA delivery including
      improved stability, facilitated internalization, promoted endosomal escape,
      increased nuclear localization, and GSH-responsive release, which contributed to
      their superior performance in terms of apoptosis promotion, proliferation
      inhibition, and Survivin down-regulation of tumor cells. More importantly, in
      hepatoma-bearing mice, orally delivered CHC NC overweighed chitosan counterparts
      with respect to suppressed Survivin expression, retarded tumor growth, and
      prolonged surviving time, owing to their above-mentioned merits in combination
      with enhanced intestinal permeation. Especially, rapid intracellular release of
      CHC NC with lower molecular weight of 30 kDa (CHC30 NC) might be responsible for
      the most satisfactory antitumor efficacy with tumor inhibition ratio (TIR) of
      92.5%, which rendered CHC30 NC a promising vehicle for oral delivery of shRNA.
      This investigation would shed light on the deliberate design of oral shRNA
      delivery vehicles to mediate effective antitumor efficacy. 

PMID- 26310109
TI  - Cross-modal synaptic plasticity in adult primary sensory cortices.
AB  - Sensory loss leads to widespread adaptation of brain circuits to allow an
      organism to navigate its environment with its remaining senses, which is broadly
      referred to as cross-modal plasticity. Such adaptation can be observed even in
      the primary sensory cortices, and falls into two distinct categories: recruitment
      of the deprived sensory cortex for processing the remaining senses, which we term
      'cross-modal recruitment', and experience-dependent refinement of the spared
      sensory cortices referred to as 'compensatory plasticity.' Here we will review
      recent studies demonstrating that cortical adaptation to sensory loss involves
      LTP/LTD and homeostatic synaptic plasticity. Cross-modal synaptic plasticity is
      observed in adults, hence cross-modal sensory deprivation may be an effective way
      to promote plasticity in adult primary sensory cortices. 

PMID- 26310110
TI  - Synapse-type-specific plasticity in local circuits.
AB  - Neuroscientists spent decades debating whether synaptic plasticity was
      presynaptically or postsynaptically expressed. It was eventually concluded that
      plasticity depends on many factors, including cell type. More recently, it has
      become increasingly clear that plasticity is regulated at an even finer grained
      level; it is specific to the synapse type, a concept we denote synapse-type
      specific plasticity (STSP). Here, we review recent developments in the field of
      STSP, discussing both long-term and short-term variants and with particular
      emphasis on neocortical function. As there are dozens of neocortical cell types,
      there is a multiplicity of forms of STSP, the vast majority of which have never
      been explored. We argue that to understand the brain and synaptic diseases, we
      have to grapple with STSP. 

PMID- 26310112
TI  - [See the strabismus and amblyopia research development trend from the twelfth
      World Congress of strabismus].
AB  - The International strabismus association conference has a history of fifty years
      until now. It's the most influential academic communication forum for the
      worldwide doctors and related scientists or technical carers in strabismus and
      amblyopia area. The conference gathered the top-level experts. The latest
      clinical/research achievements of strabismus, amblyopia in the field of binocular
      vision and ocular motility have been showed. The breakthroughs in the etiology
      study of incomitant strabismus have been and are being transformed into new
      therapeutic concepts and techniques. Re-adjust the competition between dominant
      and amblyopic eye using binocular stimulation methods may overcome the existing
      defects of monocular occlusion therapy, expand new interventional methods to
      treat amblyopia, and represent the future trends of amblyopia therapy. In this
      paper, we will introduce the main contents of the XII ISA meeting and spread
      knowledge of strabismus/amblyopia promoting directions in order to provide
      reference ideas for the clinicians and research colleagues in this field. 

PMID- 26310113
TI  - [Interpretation the consensus of strabismus classification].
AB  - Strabismus is a deviation of the visual axes relative to each other and is a very
      common eye disease. Strabismus is not only a cosmetic disease but more
      importantly damage to visual acuity, binocular vision and stereopsis. There are
      many different strabismus forms. It is very difficult to accommodate all the
      different clinical forms with only one classification. Different author has
      different classification because of different concerns. In order to avoid
      clinical confusion and provide references for clinicians, literatures from
      mainstream domestic and international journals and new revised classification by
      Chinese Association for Strabismus and Pediatric Ophthalmology were reviewed in
      this paper. 

PMID- 26310111
TI  - Mitochondrial uncoupling links lipid catabolism to Akt inhibition and resistance
      to tumorigenesis.
AB  - To support growth, tumour cells reprogramme their metabolism to simultaneously
      upregulate macromolecular biosynthesis while maintaining energy production.
      Uncoupling proteins (UCPs) oppose this phenotype by inducing futile mitochondrial
      respiration that is uncoupled from ATP synthesis, resulting in nutrient wasting.
      Here using a UCP3 transgene targeted to the basal epidermis, we show that forced
      mitochondrial uncoupling inhibits skin carcinogenesis by blocking Akt activation.
      Similarly, Akt activation is markedly inhibited in UCP3 overexpressing primary
      human keratinocytes. Mechanistic studies reveal that uncoupling increases fatty
      acid oxidation and membrane phospholipid catabolism, and impairs recruitment of
      Akt to the plasma membrane. Overexpression of Akt overcomes metabolic regulation
      by UCP3, rescuing carcinogenesis. These findings demonstrate that mitochondrial
      uncoupling is an effective strategy to limit proliferation and tumorigenesis
      through inhibition of Akt, and illuminate a novel mechanism of crosstalk between
      mitochondrial metabolism and growth signalling. 

PMID- 26310114
TI  - [The effect of superior oblique tucking on the status of ocular torsion].
AB  - OBJECTIVE: To investigate the effect of superior oblique tucking on the status of
      ocular torsion. METHODS: It was a retrospective case series study. We reviewed
      the records of 25 patients underwent superior oblique tucking for treatment of
      superior oblique palsy in Tianjin Eye Hospital from January 2012 to and August
      2013, among them, there were 12 patients had undergone inferior oblique myectomy
      or inferior rectus recession before this operation. All clinical records,
      including eye movement, vertical deviation, abnormal head position, Bielschowsky
      test et al were analyzed. Objective cyclotorsion were examined pre-operation, as
      well as 1, 30 days post-operation with fundus photograph. The photographs were
      transferred to a computer and then the fovea-disa angle (FDA) was measured by a
      software for drawing pictures. The difference of the two eyes was compared by the
      paired t-test, and the difference of the two groups was compared by the one-way
      analysis of variance. RESULTS: All patients had no more than 12 PD vertical
      deviation and significant abnormal head position before the operations. After
      underwent superior oblique tucking from 6 mm to 10 mm, their vertical deviation
      were less than 3 PD, and symptom of unacceptable abnormal head position were
      ameliorated or disappeared. In 25 cases of the monocular eye involvement, FDA was
      -10.60 degrees  +/- 4.93 degrees  in the affected eyes preoperatively, while it
      was -9.67 degrees  +/- 5.47 degrees  in the fellow eyes. There was also no
      statistically significant difference between two eyes (t = 0.54, P = 0.59). The
      combined FDA in both eyes were -20.27 degrees  +/- 6.00 degrees  and -10.53
      degrees  +/- 8.04 degrees , -10.83 degrees  +/- 7.38 degrees  preoperatively, 1,
      and 30 days after operation. The comparison of objective ocular cyclotorsion for
      both eyes showed significant difference pre- and post-operation (F = 14.81, P <
      0.01). CONCLUSIONS: Superior oblique tucking can correct ocular excyclodeviation
      effectively, and simultaneously correct little vertical deviation. It's good to
      ameliorate abnormal head position.

PMID- 26310115
TI  - [Treatment of large hypertropia following absence of inferior rectus by
      integrated anteriorization of inferior oblique combined with recession of
      superior rectus].
AB  - OBJECTIVE: To evaluate the effect of integrated anteriorization of inferior
      oblique muscle combined with recession of superior rectus to treat large
      hypertropia following absence of inferior rectus. METHODS: It was a retrospective
      case series study. Integrated anteriorization of inferior oblique muscle means
      transposing inferior oblique muscle 8-10 mm posterior to the insertion directly
      to original insertion of inferior rectus without myotomy. We reviewed 5 patients
      with absence of inferior rectus muscle, who treated by integrated anteriorization
      of inferior oblique muscle combined with recession of superior rectus. The pre
      and post-operative vertical deviation in primary position, ocular motility, and
      abnormal head position were compared. The patients were followed up from 6 to 18
      months, with average as 10.8 months. RESULTS: Postoperatively, 4 patients showed
      orthophoria in primary position and 1 patient had 10 PD hypotropia. The
      infraduction deficits improved from -3.0 to -1.6. Meanwhile, there had been an
      average of -2.0 mild supraduction limitation. Abnormal head position (AHP)
      disappeared in 2 patients with AHP before operation. All the patients showed no
      change of cyclodeviation on fundus photograph. 5 patients were satisfied with the
      improvement of the appearance, and the follow-up results were stable, no other
      surgery again. CONCLUSIONS: Integrated anteriorization of inferior oblique muscle
      combined with recession of superior rectus was an effective surgical selection to
      treat hypertropia with absence of inferior rectus muscle. This procedure doesn't
      need to cut off the inferior oblique muscle. The more convenient surgical
      procedure can reduce the risk of bleeding.

PMID- 26310116
TI  - [Brown syndrome: clinical and radiological correlation].
AB  - OBJECTIVE: Brown syndrome is characterized by limitation of elevation in
      adduction, with complex mechanisms involving muscle, tendon, and trochlea. Here,
      we investigated mechanisms of Brown syndrome by magnetic resonance (MR) imaging.
      METHODS: It was a retrospective case series study. Fourteen patients with
      unilateral Brown syndrome between 3 and 54 years of age (10 cases of congenital
      and 4 cases with acquired disease) were included in the study. All patients
      underwent complete ophthalmic and orthoptic evaluation. Imaging of the ocular
      motor nerves at the brainstem was performed on 3D-FIESTA sequence, the orbits
      were imaged with FSE T1, T2WI using surface coils. RESULTS: Nine of 10 with
      congenital Brown syndrome demonstrated hypoplasia of the superior oblique (SO) of
      the affected side. Abnormal low signal intensity in the trochlea area was found
      in one patient. Three of 4 acquired patients had a history of trauma and were
      demonstrated fracture of the trochlea, extensive scarring, and superior orbital
      fracture. One acquired case was demonstrated scarring of anterior part of the SO
      and hypoplasia of the posterior part. CONCLUSION: Brown syndrome consists of a
      series of diseases. Their clinical features are quite similar while their
      anatomical mechanism varies in numerous ways. Therefore, based on patient's
      individual pathophysiology, the management in Brown syndrome should be
      personalized.

PMID- 26310117
TI  - [MRI study of the thickness and width of the extraocular muscles in normal
      subjects].
AB  - OBJECTIVE: To study the thickness and width of extraocular muscles by high
      resolution magnetic resonance imaging (MRI). METHODS: Cross-sectional study.
      Sixty eight normal subjects between 2.0 and 50.0 years of age, mean age was (21.2
      +/- 2.1) (SD) years old, male 34, female 34. Extraocular muscles in the orbits
      were scanned with SE/T2WI coronal and oblique-coronal planes perpendicular to
      optic nerve, and within 1.5 mm thick planes. The thickness and width of the
      extraocular muscles in the maximum planes were measured in 68 normal subjects on
      oblique-coronal planes MR images. The vertical diameter of the medial rectus
      muscle and lateral rectus muscle indicated width, horizontal diameter indicated
      thickness. The vertical diameter of the superior rectus muscle and inferior
      rectus muscle indicated thickness, horizontal diameter indicated width. Vertical
      diameter of the muscle belly is from the top edge to the bottom edge, horizontal
      diameter of the muscle belly is from the innermost to the outermost edge. The
      differences in diameters of bilateral extraocular muscles were evaluated by the
      independent sample t statistical test. Superior oblique muscle was considered as
      a reference in each subject to calculate the ratio of the other rectus muscles
      and the superior oblique muscle in diameter and to compare the relationship of
      the extraocular muscles in the same plane. RESULTS: The extraocular muscles of
      normal subjects were symmetrical on the two sides. There were no statistically
      significant differences between the bilateral extraocular muscles (medial rectus
      muscle, lateral rectus muscle, inferior rectus muscle and superior rectus muscle)
      in the thickness and width (t values respectively were 0.043, 0.025, 0.043,
      0.032, 0.001, 0.601, 0.667, 0.021, 0.032, 0.005, all P > 0.05). The ratio of the
      rectus muscles (medial rectus muscle, lateral rectus muscle, superior rectus
      muscle, inferior rectus muscle) and the superior oblique muscle in thickness
      respectively were (1.15 +/- 0.14), (1.04 +/- 0.14), (1.07 +/- 0.19), (1.39 +/-
      0.22). The relationship of the thickness of extraocular muscles in the maximum
      planes were: inferior rectus muscle > medial rectus muscle > superior rectus
      muscle > lateral rectus muscle, and the thickness of 91% superior rectus muscle
      was close to lateral rectus muscle. The ratio of the rectus muscles (medial
      rectus muscle, lateral rectus muscle, superior rectus muscle, inferior rectus
      muscle) and the superior oblique muscle in width respectively were (1.71 +/-
      0.27), (2.07 +/- 0.28), (1.62 +/- 0.29), (1.50 +/- 0.21). The relationship of the
      width of extraocular muscles in the maximum planes were: lateral rectus muscle >
      medial rectus muscle > superior rectus muscle > inferior rectus muscle.
      CONCLUSIONS: The thickness and width of all the extraocular muscles follows a
      certain rule. Measurements of extraocular muscles using MRI should be done on
      coronal and oblique-coronal planes MRI scan simultaneously. The sizes of
      extraocular muscles can be assessed by observing the symmetry of the extraocular
      muscles on the two sides on coronal plane and the usual rule of extraocular
      muscles on oblique-coronal plane.

PMID- 26310118
TI  - [Quantitative assess the efficacy of congenital idiopathic nystagmus surgery by
      digital eye tracker].
AB  - OBJECTIVE: To evaluate the feasibility of independently developed digital eye
      tracker in determining the efficacy of congenital idiopathic nystagmus (CIN)
      surgery. METHODS: Aprospective selfpairing study. The surgical efficacy was
      evaluated by independently developed eye tracker in 16 CIN patients. The null
      zone and the frequency, amplitude, intensity of nystagmus in various gazing
      position were recorded with eye tracker pre and post operatively. The consistency
      of null zone determined by digital eye tracker and clinical investigation were
      evaluated. The preoperative and postoperative rectification of horizontal and
      vertical nystagmus in the horizontal direction of individual patient were
      compared by paired samples t-test. The improvement or aggravation quantity were
      recorded by comparing preoperative and postoperative intensity of nystagmus every
      5 degrees  within 25 degrees . RESULT: The null zone got from digital eye tracker
      and clinical investigation were highly consistent (r = 0.952, P < 0.01). The
      horizontal and vertical intensity improved in 9 patients (t = 2.335-6.609, P <
      0.05) and 5 patients (t = 2.176-5.471, P < 0.05) respectively after surgery.
      There were 67.63% (117/173) horizontal intensity and 69.94% (121/173) vertical
      intensity improvement. CONCLUSION: The independently developed digital eye
      tracker can quantitatively evaluate the pre and post-operative nystagmus and
      analyze the surgical efficacy for CIN patients.

PMID- 26310119
TI  - [Clinical results of femtosecond laser assisted lamellar keratoplasty].
AB  - OBJECTIVE: To report the clinical results of femtosecond laser assisted lamellar
      keratoplasty (FS-LK). METHODS: Retrospective study. Twenty eyes of 17 patients
      who were treated with FS-LK were enrolled in this study. The preoperative visions
      were from 0.02 to 0.4. During the operation, the grafts were prepared with a
      depth of 400-600 um according to the character of the affections. RESULTS: During
      the follow-up period, the visions of 18 eyes (90%) were better than preoperative
      ones. One of them was equal to 0.8. The best corrected visual acuities of 18 eyes
      (90%) were better than or equal to 0.5, one of which was 1.0. The astigmatisms of
      15 eyes were under 3.00 diopters at one year after operation. During the
      operation of two cases, the paracentral cut occurred. Two patients experienced
      corneal opacity, and two cases had high astigmatisms after operation. Only one
      eye experienced immune rejection at one year after operation. CONCLUSIONS: The FS
      LK appears to be a good alternative surgical method for patients with corneal
      diseases because of the great manipuility and excellent postoperative results,
      but more research is needed.

PMID- 26310120
TI  - [Investigation on the concentration of riboflavin in sclera tissue].
AB  - OBJECTIVE: To investigate the permeability and saturation characteristics of
      riboflavin in sclera tissue, in order to explore a reasonable dosage regimen in
      sclera cross-linking. METHODS: Experimental study. Five human cadaver eyes were
      also included in this study, every eye was cut into seven sclera stripes and then
      0.1% riboflavin solution was dripped to the sclera stripes for 5, 10, 15, 20, 25,
      30 minutes respectively. After that, the stripes were made into frozen sections
      and observed by confocal microscope. To calculate the mean fluorescence density
      and compare with each other. In addition, 36 New Zealand rabbits were randomly
      divided into group A and B groups. Each group was divided into six subgroups. In
      group A, 0.1% riboflavin solution was dripped to the sclera of right eye for 5,
      10, 15, 20, 25 and 30 minutes respectively. In group B, 0.5% ribof lavin solution
      was dripped to the sclera of right eye for 5, 10, 15, 20, 25 and 30 minutes
      respectively. The left eye were given with physiological saline as blank check.
      Executed the rabbits to take out the eye and then the nose upper quadrant of the
      equator sclera was taken to made into frozen sections which were observed by two
      photon microscope. To calculate the mean fluorescence density and compare the six
      subgroups in every group respectively, and compare the subgroups with the same
      riboflavin-applicated time between group A and B respectively. RESULTS: The
      fluorescence intensity of sclera gradually strengthened with the longer
      riboflavin-applicated time, but there was no statistical difference between 20
      minutes and the longer time groups (P > 0.05). With the same riboflavin
      applicated time in rabbit sclera, the fluorescence intensity of 0.5%
      concentration group was higher than 0.1% concentration group (P < 0.05).
      CONCLUSIONS: The riboflavin reached an saturation level in the sclera of human
      cadaver eyes and rabbit eyes after 20 minutes application. The higher
      concentration of riboflavin-applicated, the higher concentration of riboflavin in
      the rabbit sclera.

PMID- 26310121
TI  - [Study of guinea pig refractive status and ocular length during the early
      recovery from lens-induced myopia].
AB  - OBJECTIVE: To investigate changes in refractive status and ocular length in
      guinea pigs during the early time of myopic recovery for the causes of recovery.
      METHODS: Exp guinea pigs wore a -5.00 D lens on one eye from 4-18 days, which was
      then removed for 48 hours. At 18 and 20 days of age, each eye was evaluated for
      refractive status and ocular length of the eye. RESULTS: The right eyes treated
      with -5 D lenses for 12 days developed (-2.00 +/- 1.50) D (P = 0.04) of myopia
      and had an increase in axial length of (0.033 +/- 0.025) mm compared to the left
      eyes (P = 0.04). After 48 hours of recovery, the difference between the two eyes
      was reduced to (-0.72 +/- 0.86) D (P = 0.13), but the ocular length still had
      significant difference (0.031 +/- 0.022) mm (P = 0.04). During the myopia
      recovery early period, the refractive status and ocular length changed in the
      same direction in the left eyes but in the opposite way in the right eyes.
      CONCLUSIONS: Guinea pigs treated with -5.00 D lenses for 12 days developed
      explicit relative axial myopia. After removal of the lens for 48 hours, myopia
      significantly recovery can be due to the thickening of choroid and the reduction
      in ocular growth.

PMID- 26310122
TI  - [Hot topics in treatment of intermittent exotropia].
AB  - Intermittent exotropia is the most common type of exotropia, and also is one of
      the most difficult types of strabismus to deal with. Surgery is the main choice
      of treatment and non-surgical treatment is used only under certain indications.
      Long-term outcomes of the surgery for intermittent exotropia are related to many
      factors, such as age, course of the disease, perceptual state of visual cortex,
      timing of surgery, types of intermittent exotropia, the surgical methods,
      preoperative measurements of exodeviations, target angle of surgery,
      postoperative treatment of overcorrection or undercorrection, and so on. It is
      significant to pay attention to these issues to improve success rate of the
      surgeries. In this paper, recent progress of clinical studies of intermittent
      exotropia were reviewed to arouse the attentions of domestic ophthalmologist to
      the standardization of diagnosis and treatment of intermittent exotropia. 

PMID- 26310123
TI  - [The developmental switch of visual cortex NMDA receptor NR2 subunits and its
      implications for visual plasticity].
AB  - Many forms of synaptic plasticity require NMDA-type glutamate receptors (NMDAR).
      These tetrameric receptors consist of two obligatory NR1 subunits and two
      regulatory subunits, usually a combination of NR2A and NR2B. In the neonatal
      visual cortex NR2B-containing NMDAR predominate, after thatvisual experience
      facilitates a developmental switch in which NR2A levels increase relative to
      NR2B. In this review, it puts emphasis on the role and the regulation of this
      shift as well as the effect on synaptic plasticity. 

PMID- 26310124
TI  - [Research advances on relationship between ocular perfusion pressure fluctuations
      and glaucoma].
AB  - Intraocular pressure (IOP) is considered the main risk factor for the development
      and progression of glaucoma. The major treatment is to reduce the intraocular
      pressure. However, the damage of optic nerve may continue to progress despite
      lowering patients' IOP to the target levels. High ocular perfusion pressure (OPP)
      fluctuations could have detrimental effects in eyes with glaucoma which confirmed
      that vascular factor is one of the pathogenesis of glaucoma. This review article
      discussed the research progress of relationship between ocular perfusion pressure
      and glaucoma including its definition, calculation, epidemiological studies,
      fluctuation and autoregulation. We also discussed whether it was secondary to
      changes in intraocular pressure, blood pressure or both. We expect ocular
      perfusion pressure fluctuations could provide evidence for evaluating glaucoma
      progress. 

PMID- 26310126
TI  - Butyltin and PAH Contamination of Mar del Plata Port (Argentina) Sediments and
      Their Influence on Adjacent Coastal Regions.
AB  - The distribution of butyltins (BTs) and polycyclic aromatic hydrocarbons (PAHs)
      were studied in surface sediments to assess how relevant is Mar del Plata port
      (Argentina) as a source of contamination to the surrounding environments. Within
      the port, TBT concentrations ranged from 24.2 to 150 ng Sn g(-1) and PAHs
      (Sigma16) from 180 to 17,094 ng g(-1). At the surrounding beaches, PAHs were
      detected at low concentrations and TBT concentrations reached 10.9 ng Sn g(-1).
      Although those low levels indicate that the Port might not be an important source
      of contamination to the surrounding beaches, the very low TOC content and the
      coarse grain size of the beaches sediments could explain the sedimentary levels.
      The results show a reduction in TBT levels in Mar del Plata port after national
      and international use restrictions of TBT-based antifouling paints. 

PMID- 26310125
TI  - The RNA-binding protein Sam68 regulates expression and transcription function of
      the androgen receptor splice variant AR-V7.
AB  - Castration-resistant (CR) prostate cancer (PCa) partly arises due to persistence
      of androgen receptor (AR) transcriptional activity in the absence of cognate
      ligand. An emerging mechanism underlying the CRPCa phenotype and predicting
      response to therapy is the expression of the constitutively-active AR-V7 splice
      variant generated by AR cryptic exon 3b inclusion. Here, we explore the role of
      the RNA-binding protein (RBP) Sam68 (encoded by KHDRBS1), which is over-expressed
      in clinical PCa, on AR-V7 expression and transcription function. Using a minigene
      reporter, we show that Sam68 controls expression of exon 3b resulting in an
      increase in endogenous AR-V7 mRNA and protein expression in RNA-binding-dependent
      manner. We identify a novel protein-protein interaction between Sam68 and AR-V7
      mediated by a common domain shared with full-length AR, and observe these
      proteins in the cell nucleoplasm. Using a luciferase reporter, we demonstrate
      that Sam68 co-activates ligand-independent AR-V7 transcriptional activity in an
      RNA-binding-independent manner, and controls expression of the endogenous AR-V7
      specific gene target UBE2C. Our data suggest that Sam68 has separable effects on
      the regulation of AR-V7 expression and transcriptional activity, through its RNA
      binding capacity. Sam68 and other RBPs may control expression of AR-V7 and other
      splice variants as well as their downstream functions in CRPCa. 

PMID- 26310127
TI  - Cadmium Toxicity and Alleviating Effects of Exogenous Salicylic Acid in Iris
      hexagona.
AB  - Cadmium (Cd) toxictity and possible role of salicylic acid (SA) in alleviating Cd
      induced toxicity were investigated on ornamental hydrophyte Iris hexagona.
      Compared to the control, treatments with 100 and 500 uM Cd for 7 days
      significantly decreased dry weight, the contents of chlorophyll, photosynthetic
      parameters, and increased the content of thiobarbituric acid reactive substance.
      Pretreatment of the roots of I. hexagona seedlings with 1 uM SA before Cd
      exposure may increase dry weight, photosynthetic rate, activities of antioxidant
      enzymes, improve the cell ultrastructure and protect plants from Cd-induced
      oxidative stress damage. However, SA pretreatment had no significant effect on Cd
      concentrations in the leaves and roots. It is suggested that SA-induced Cd
      tolerances in I. hexagona are likely associated with increases in antioxidant
      enzyme activities and vacuolar compartmentation, rather than Cd uptake. 

PMID- 26310128
TI  - Toxic Assessment of Triclosan and Triclocarban on Artemia salina.
AB  - In this study, we investigated the possible acute toxic and genotoxic effects of
      triclosan (TCS) and triclocarban (TCC) on Artemia salina. Genotoxicity was
      evaluated using single-cell gel electrophoresis and apoptotic frequency assays
      (Annexin V-FITC/PI assay). Acute toxicity test results showed that TCC (LC50-24 h
      = 17.8 ug/L) was more toxic than TCS (LC50-24 h = 171.1 ug/L). Significant
      increases in both genotoxic biomarkers were observed at 24 h after initial
      exposure, indicating that these two chemicals are potentially dangerous for this
      aquatic biological model. Although further studies are required, a comparison of
      data both in vitro and in vivo allowed us to suggest possible mechanisms of
      action for TCS and TCC in this sentinel organism. 

PMID- 26310129
TI  - Chromosome arrangement, differentiation of growth kinetics and volatile molecule
      profiles in Kluyveromyces marxianus strains from Italian cheeses.
AB  - Thirty-nine strains of Kluyveromyces marxianus from Pecorino di Farindola cheese
      in comparison with 3 strains from Parmigiano Reggiano cheese, 1 from fermented
      milk, 3 from cow whey and two type strains K. marxianus CBS 834(T) and
      Kluyveromyces lactis CBS 683(T) were tested for genetic and metabolic
      characteristics. Intraspecific diversity of chromosome arrangements was evaluated
      by pulsed field gel electrophoresis (PFGE) analysis. Among K. marxianus strains
      chromosome polymorphisms were evident with 11 patterns that differed in size and
      number of the chromosomal bands. The number of the bands varied from 4 to 7 with
      sizes ranging from about 1.0 to 2.7 Mb. Twelve strains were selected for
      determining their growth capacity and volatile compound production in two wheys
      (raw cheese whey and ricotta cheese whey) under limited oxygen availability. The
      growth kinetics highlighted four different biotypes and the influence of whey
      composition on K. marxianus development. The main volatile compounds detected
      after the growth were alcohols, acids, esters, ketones and aldehydes. Ethanol was
      the most abundant in both wheys. Aldehydes and other minor compounds were
      produced only when the strains were inoculated in ricotta cheese whey, while
      esters, butanoic, decanoic and octanoic acids were qualitatively and
      quantitatively more present in raw cheese whey. This study highlights a great
      genetic and metabolic biodiversity within Pecorino di Farindola K. marxianus
      strains and it could be exploited to improve the knowledge of this yeast for
      biotechnological uses.

PMID- 26310130
TI  - Microbiota of Minas cheese as influenced by the nisin producer Lactococcus lactis
      subsp. lactis GLc05.
AB  - Minas cheese is a popular dairy product in Brazil that is traditionally produced
      using raw or pasteurized cow milk. This study proposed an alternative production
      of Minas cheese using raw goat milk added of a nisin producer Lactococcus lactis
      subsp. lactis GLc05. An in situ investigation was carried on to evaluate the
      interactions between the L. lactis subsp. lactis GLc05 and the autochthonous
      microbiota of a Minas cheese during the ripening; production of biogenic amines
      (BAs) was assessed as a safety aspect. Minas cheese was produced in two
      treatments (A, by adding L. lactis subsp. lactis GLc05, and B, without adding
      this strain), in three independent repetitions (R1, R2, and R3). Culture
      dependent (direct plating) and independent (rep-PCR and PCR-DGGE) methods were
      employed to characterize the microbiota and to assess the possible interferences
      caused by L. lactis subsp. lactis GLc05. BA amounts were measured using HPLC. A
      significant decrease in coagulase-positive cocci was observed in the cheeses
      produced by adding L. lactis subsp. lactis GLc05 (cheese A). The rep-PCR and PCR
      DGGE highlighted the differences in the microbiota of both cheeses, separating
      them into two different clusters. Lactococcus sp. was found as the main
      microorganism in both cheeses, and the microbiota of cheese A presented a higher
      number of species. High concentrations of tyramine were found in both cheeses
      and, at specific ripening times, the BA amounts in cheese B were significantly
      higher than in cheese A (p<0.05). The interaction of nisin producer L. lactis
      subsp. lactis GLc05 was demonstrated in situ, by demonstration of its influence
      in the complex microbiota naturally present in a raw goat milk cheese and by
      controlling the growth of coagulase-positive cocci. L. lactis subsp. lactis GLc05
      influenced also the production of BA determining that their amounts in the
      cheeses were maintained at acceptable levels for human consumption. 

PMID- 26310131
TI  - Randomised clinical study: gluten challenge induces symptom recurrence in only a
      minority of patients who meet clinical criteria for non-coeliac gluten
      sensitivity.
AB  - BACKGROUND: It is unknown whether symptoms in non-coeliac patients (non-CD)
      meeting clinical diagnostic criteria for noncoeliac gluten sensitivity (NCGS) are
      specifically triggered by gluten. AIM: To assess gluten sensitivity in patients
      diagnosed with NCGS. METHODS: We studied 35 non-CD subjects (31 females) that
      were on a gluten-free diet (GFD), in a double-blind challenge study. Participants
      were randomised to receive either gluten-containing flour or gluten-free flour
      for 10 days, followed by a 2-week washout period and were then crossed over. The
      main outcome measure was their ability to identify which flour contained gluten.
      Secondary outcome measures were based upon Gastrointestinal Symptoms Rating Scale
      (GSRS) scores. RESULTS: The gluten-containing flour was correctly identified by
      12 participants (34%), who were classified as having NCGS. Their mean GSRS
      dimension scores were significantly higher following gluten challenge compared to
      baseline. The scores were: pain, 1.7 +/- 0.8 vs. 2.6 +/- 1.0; reflux, 1.6 +/- 0.5
      vs. 2.2 +/- 0.9; indigestion, 1.9 +/- 0.7 vs. 3.2 +/- 1.1; diarrhoea, 1.6 +/- 0.7
      vs. 2.9 +/- 1.5 and constipation, 1.9 +/- 0.9 vs. 2.9 +/- 1.3. Seventeen
      participants (49%) erroneously considered the gluten-free flour to contain
      gluten. Their mean GSRS dimension scores were significantly higher following
      gluten-free flour challenge compared to baseline. The scores were: pain, 1.6 +/-
      0.9 vs. 3.0 +/- 0.9; reflux, 1.4 +/- 0.5 vs. 2.3 +/- 1.1; indigestion, 2.0 +/-
      1.1 vs. 3.7 +/- 1.1; diarrhoea, 1.6 +/- 0.7 vs. 3.0 +/- 1.2 and constipation, 1.6
      +/- 0.9 vs. 2.6 +/- 1.3. The other six participants (17%) were unable to
      distinguish between the flours. CONCLUSION: Double-blind gluten challenge induces
      symptom recurrence in just one-third of patients fulfilling the clinical
      diagnostic criteria for non-coeliac gluten sensitivity.

PMID- 26310133
TI  - Autobiography of Biman Bagchi.

PMID- 26310132
TI  - Tribute to Biman Bagchi.

PMID- 26310136
TI  - Publications of Biman Bagchi.

PMID- 26310137
TI  - Antennal RNA-sequencing analysis reveals evolutionary aspects of chemosensory
      proteins in the carpenter ant, Camponotus japonicus.
AB  - Chemical communication is essential for the coordination of complex organisation
      in ant societies. Recent comparative genomic approaches have revealed that
      chemosensory genes are diversified in ant lineages, and suggest that this
      diversification is crucial for social organisation. However, how such diversified
      genes shape the peripheral chemosensory systems remains unknown. In this study,
      we annotated and analysed the gene expression profiles of chemosensory proteins
      (CSPs), which transport lipophilic compounds toward chemosensory receptors in the
      carpenter ant, Camponotus japonicus. Transcriptome analysis revealed 12 CSP genes
      and phylogenetic analysis showed that 3 of these are lineage-specifically
      expanded in the clade of ants. RNA sequencing and real-time quantitative
      polymerase chain reaction revealed that, among the ant specific CSP genes, two of
      them (CjapCSP12 and CjapCSP13) were specifically expressed in the chemosensory
      organs and differentially expressed amongst ant castes. Furthermore, CjapCSP12
      and CjapCSP13 had a ratio of divergence at non-synonymous and synonymous sites
      (dN/dS) greater than 1, and they were co-expressed with CjapCSP1, which is known
      to bind cuticular hydrocarbons. Our results suggested that CjapCSP12 and
      CjapCSP13 were functionally differentiated for ant-specific chemosensory events,
      and that CjapCSP1, CjapCSP12, and CjapCSP13 work cooperatively in the antennal
      chemosensilla of worker ants. 

PMID- 26310138
TI  - Klf10 regulates odontoblast differentiation and mineralization via promoting
      expression of dentin matrix protein 1 and dentin sialophosphoprotein genes.
AB  - Klf10, a member of the Kruppel-like family of transcription factors, is critical
      for osteoblast differentiation, bone formation and mineralization. However,
      whether Klf10 is involved in odontoblastic differentiation and tooth development
      has not been determined. In this study, we investigate the expression patterns of
      Klf10 during murine tooth development in vivo and its role in odontoblastic
      differentiation in vitro. Klf10 protein was expressed in the enamel organ and the
      underlying mesenchyme, ameloblasts and odontoblasts at early and later stages of
      murine molar formation. Furthermore, the expression of Klf10, Dmp1, Dspp and
      Runx2 was significantly elevated during the process of mouse dental papilla
      mesenchymal differentiation and mineralization. The overexpression of Klf10
      induced dental papilla mesenchymal cell differentiation and mineralization as
      detected by alkaline phosphatase staining and alizarin red S assay. Klf10
      additionally up-regulated the expression of odontoblastic differentiation marker
      genes Dmp1, Dspp and Runx2 in mouse dental papilla mesenchymal cells. The
      molecular mechanism of Klf10 in controlling Dmp1 and Dspp expression is thus to
      activate their regulatory regions in a dosage-dependent manner. Our results
      suggest that Klf10 is involved in tooth development and promotes odontoblastic
      differentiation via the up-regulation of Dmp1 and Dspp transcription. 

PMID- 26310139
TI  - Soluble epoxide hydrolase inhibitor 1-trifluoromethoxyphenyl-3- (1
      propionylpiperidin-4-yl) urea attenuates bleomycin-induced pulmonary fibrosis in
      mice.
AB  - Epoxyeicosatrienoic acids (EETs), the metabolites of arachidonic acid derived
      from the cytochrome P450 (CYP450) epoxygenases, are mainly metabolized by soluble
      epoxide hydrolase (sEH) to their corresponding diols. EETs but not their diols,
      have anti-inflammatory properties and inhibition of sEH might provide protective
      effects against inflammatory fibrosis. We test the effects of a selected sEH
      inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), on
      bleomycin-induced pulmonary fibrosis (PF) in mice. A mouse model of PF was
      established by intratracheal injection of bleomycin and TPPU was administered for
      21 days after bleomycin injection. We found TPPU treatment improved the body
      weight loss and survival rate of bleomycin-stimulated mice. Histological
      examination showed that TPPU treatment alleviated bleomycin-induced inflammation
      and maintained the alveolar structure of the pulmonary tissues. TPPU also
      decreased the bleomycin-induced deposition of collagen and the expression of
      procollagen I mRNA in lung tissues of mice. TPPU decreased the transforming
      growth factor-beta1 (TGF-beta1), interleukin-1beta (IL-1beta) and IL-6 levels in
      the serum of bleomycin-stimulated mice. Furthermore, TPPU inhibited the
      proliferation and collagen synthesis of mouse fibroblasts and partially reversed
      TGF-beta1-induced alpha-smooth muscle actin expression. Our results indicate that
      the inhibition of sEH attenuates bleomycin-induced inflammation and collagen
      deposition and therefore prevents bleomycin-induced PF in a mouse model.

PMID- 26310141
TI  - POLYAMINE OXIDASE2 of Arabidopsis contributes to ABA mediated plant developmental
      processes.
AB  - Polyamines (PA) are catabolised by two groups of amine oxidases, the copper
      binding amine oxidases (CuAOs) and the FAD-binding polyamine oxidases (PAOs).
      Previously, we have shown that CuAO1 is involved in ABA associated growth
      responses and ABA- and PA-mediated rapid nitric oxide (NO) production. Here we
      report the differential regulation of expression of POLYAMINE OXIDASE2 of
      Arabidopsis (AtPAO2) in interaction with ABA, nitrate and ammonium. Without ABA
      treatment germination, cotyledon growth and fresh weight of pao2 knockdown
      mutants as well as PAO2OX over-expressor plants were comparable to those of the
      wild type (WT) plants irrespective of the N source. In the presence of ABA, in
      pao2 mutants cotyledon growth and fresh weights were more sensitive to inhibition
      by ABA while PAO2OX over-expressor plants showed a rather similar response to WT.
      When NO3(-) was the only N source primary root lengths and lateral root numbers
      were lower in pao2 mutants both without and with exogenous ABA. PAO2OX showed
      enhanced primary and lateral root growth in media with NO3(-) or NH4(+). Vigorous
      root growth of PAO2OX and the hypersensitivity of pao2 mutants to ABA suggest a
      positive function of AtPAO2 in root growth. ABA-induced NO production in pao2
      mutants was lower indicating a potential contributory function of AtPAO2 in NO
      mediated effects on root growth. 

PMID- 26310140
TI  - The border-to-border distribution method for analysis of cytoplasmic particles
      and organelles.
AB  - Comparing the distribution of cytoplasmic particles and organelles between
      different experimental conditions can be challenging due to the heterogeneous
      nature of cell morphologies. The border-to-border distribution method was created
      to enable the quantitative analysis of fluorescently labeled cytoplasmic
      particles and organelles of multiple cells from images obtained by confocal
      microscopy. The method consists of four steps: (1) imaging of fluorescently
      labeled cells, (2) division of the image of the cytoplasm into radial segments,
      (3) selection of segments of interest, and (4) population analysis of
      fluorescence intensities at the pixel level either as a function of distance
      along the selected radial segments or as a function of angle around an annulus.
      The method was validated using the well-characterized effect of brefeldin A (BFA)
      on the distribution of the vesicular stomatitis virus G protein, in which
      intensely labeled Golgi membranes are redistributed within the cytoplasm.
      Surprisingly, in untreated cells, the distribution of fluorescence in Golgi
      membrane-containing radial segments was similar to the distribution of
      fluorescence in other G protein-containing segments, indicating that the presence
      of Golgi membranes did not shift the distribution of G protein towards the
      nucleus compared to the distribution of G protein in other regions of the cell.
      Treatment with BFA caused only a slight shift in the distribution of the
      brightest G protein-containing segments which had a distribution similar to that
      in untreated cells. Instead, the major effect of BFA was to alter the annular
      distribution of G protein in the perinuclear region. 

PMID- 26310142
TI  - Roles of DgD14 in regulation of shoot branching in chrysanthemum (Dendranthema
      grandiflorum 'Jinba').
AB  - Shoot branching plays an important role in determining plant architecture.
      Strigolactones (SLs) negatively regulate shoot branching, and can respond to
      conditions of low or absent phosphate or nitrogen. The D14 gene is a probable
      candidate as an SL receptor in rice, petunia, and Arabidopsis. To investigate the
      roles of D14 in shoot branching of chrysanthemum, we isolated the D14 homolog
      DgD14. Functional analysis showed that DgD14 was a nuclear-localized protein, and
      restored the phenotype of Arabidopsis d14-1. Exogenous SL (GR24) could down
      regulate DgD14 expression, but this effect could be overridden by apical auxin
      application. Decapitation could down-regulate DgD14 expression, but this effect
      could be restored by exogenous auxin. In addition, DgD14 transcripts produced
      rapid responses in shoot and root under conditions of phosphate absence, but only
      a mild variation in bud and stem with low nitrogen treatment. Indistinct
      reductions of P levels in shoot were observed in plants grown under low nitrogen
      conditions. The absence of phosphate and low levels of nitrogen negatively
      affected plant growth. These results demonstrate that P levels in shoot had a
      close relationship with phosphate, whereas nitrogen did not directly regulate
      DgD14 expression in shoot. Taken together, these results demonstrated that DgD14
      was the functional strigolactone signaling component in chrysanthemum. 

PMID- 26310143
TI  - Whole-exome sequencing identifies USH2A mutations in a pseudo-dominant Usher
      syndrome family.
AB  - Usher syndrome (USH) is an autosomal recessive (AR) multi-sensory degenerative
      disorder leading to deaf-blindness. USH is clinically subdivided into three
      subclasses, and 10 genes have been identified thus far. Clinical and genetic
      heterogeneities in USH make a precise diagnosis difficult. A dominant-like USH
      family in successive generations was identified, and the present study aimed to
      determine the genetic predisposition of this family. Whole-exome sequencing was
      performed in two affected patients and an unaffected relative. Systematic data
      were analyzed by bioinformatic analysis to remove the candidate mutations via
      step-wise filtering. Direct Sanger sequencing and co-segregation analysis were
      performed in the pedigree. One novel and two known mutations in the USH2A gene
      were identified, and were further confirmed by direct sequencing and co
      segregation analysis. The affected mother carried compound mutations in the USH2A
      gene, while the unaffected father carried a heterozygous mutation. The present
      study demonstrates that whole-exome sequencing is a robust approach for the
      molecular diagnosis of disorders with high levels of genetic heterogeneity. 

PMID- 26310144
TI  - AT1R A1166C variants in patients with type 2 diabetes mellitus and diabetic
      nephropathy.
AB  - BACKGROUND: There are inconsistent reports related to the role of angiotensin II
      type 1 receptor (AT1R) on the risk of type 2 diabetes mellitus (T2DM) and its
      renal complications. OBJECTIVES: To identify the association between AT1R A1166C
      variants with the risk of T2DM and also with diabetic nephropathy (DN). PATIENTS
      AND METHODS: In a case-control study, the AT1R A1166C polymorphism was detected
      in 135 T2DM patients with and without DN and in 98 healthy subjects from Western
      Iran. The genotypes of AT1R A1166C polymorphism were detected using polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.
      RESULTS: The frequencies of AT1R A1166C genotypes and alleles were not
      significantly difference between patients with and without DN and controls. The
      frequencies of rare allele of 1166 C were 10%, 16.5%, 15.9% and 15.3% in micro-,
      macro- and normo-albuminuric patients and in healthy individuals, respectively (
      P > 0.05). The systolic blood pressure and serum creatinine level in DN patients
      were significantly higher in carriers of AT1R CC compared to carriers of AT1R AA
      genotype. In the presence of uncontrolled hyperglycemia (HbA1c > 7.5%), there was
      a trend toward increased risk of macro-albuminuria in carriers of AC+CC genotype
      (OR=3.66, [95% CI: 0.81-16.58], P = 0.092). CONCLUSIONS: Our study indicated the
      absence of an association between AT1R A1166C polymorphism with the risk of T2DM
      and DN. It seems in carriers of AT1R C allele systolic blood pressure and serum
      creatinine level to be higher compared to the A allele carriers.

PMID- 26310145
TI  - Overview of the Visual System.
AB  - This introduction provides an overview of the retina, in which we survey the
      fundus, layers of the retina, retinal cell types, visual transduction cascade,
      vitamin A cycle, neuronal wiring of the retina, and blood supply of the retina. 

PMID- 26310146
TI  - Overview of the Cornea: Structure, Function, and Development.
AB  - The cornea is a transparent tissue with significant refractive and barrier
      functions. The epithelium serves as the principal barrier to fluid and pathogens,
      a function performed through production of tight junctions, and constant
      repopulation through differentiation and maturation of dividing cells in its
      basal cell layer. It is supported posteriorly by basement membrane and Bowman's
      layer and assists in maintenance of stromal dehydration. The stroma composes the
      majority of corneal volume, provides support and clarity, and assists in ocular
      immunity. The posterior cornea, composed of Descemet membrane and endothelium, is
      essential for stromal dehydration, maintained through tight junctions and
      endothelial pumps. Corneal development begins with primitive formation of
      epithelium and lens, followed by waves of migration from cells of neural crest
      origin between these two structures to produce the stroma and endothelium.
      Descemet membrane is secreted by the latter and gradually thickens. 

PMID- 26310148
TI  - Corneal Development: Different Cells from a Common Progenitor.
AB  - Development of the vertebrate cornea is a multistep process that involves
      cellular interactions between various ectodermal-derived tissues. Bilateral
      interactions between the neural ectoderm-derived optic vesicles and the cranial
      ectoderm give rise to the presumptive corneal epithelium and other epithelia of
      the ocular surface. Interactions between the neural tube and the adjacent
      ectoderm give rise to the neural crest cells, a highly migratory and multipotent
      cell population. Neural crest cells migrate between the lens and presumptive
      corneal epithelium to form the corneal endothelium and the stromal keratocytes.
      The sensory nerves that abundantly innervate the corneal stroma and epithelium
      originate from the neural crest- and ectodermal placode-derived trigeminal
      ganglion. Concomitant with corneal innervation is the formation of the limbal
      vascular plexus and the establishment of corneal avascularity. This review
      summarizes historical and current research to provide an overview of the genesis
      of the cellular layers of the cornea, corneal innervation, and avascularity. 

PMID- 26310149
TI  - Corneal Epithelial Wound Healing.
AB  - The cornea is important for a clear vision by refracting light onto the lens,
      which in turn focusing on the retina. To maintain a smooth optical surface,
      corneal epithelium has to continuously renew itself to function as a barrier so
      that it protects the eye from various environmental insults. The adult corneal
      epithelium is maintained homeostatically by an integrated process of cell
      proliferation, migration, differentiation, stratification, and
      desquamation/apoptosis. Impairment of this process results in persistent corneal
      defect, leading to the blindness. Researches throughout the years revealed that
      appropriate integration and coordination of cell signaling events are responsible
      for corneal epithelial renewal and wound healing. In this chapter, we will review
      works done on cell culture, animal models, and human trials to focus on the
      signaling network during corneal wound healing process which will have potential
      for the discovery of novel drug to improve corneal wound healing. 

PMID- 26310147
TI  - Stem Cells in the Cornea.
AB  - The cornea is the tough, transparent tissue through which light first enters the
      eye and functions as a barrier to debris and infection as well as two-thirds of
      the refractive power of the eye. Corneal damage that is not promptly treated will
      often lead to scarring and vision impairment. Due to the limited options
      currently available to treat corneal scars, the identification and isolation of
      stem cells in the cornea has received much attention, as they may have potential
      for autologous, cell-based approaches to the treatment of damaged corneal tissue.

PMID- 26310150
TI  - Corneal Dystrophies: Overview and Summary.
AB  - In this chapter, I shall discuss the genetics, mode of inheritance and molecular
      origin of several corneal dystrophies. 

PMID- 26310151
TI  - Fuchs Corneal Dystrophy.
AB  - Fuchs corneal dystrophy (FCD) is a hereditary, progressive disease of the
      posterior cornea which results in excrescences of Descemet membrane, endothelial
      cell loss, corneal edema, and, in late stages, bullous keratopathy. Structural
      changes are noted principally in Descemet membrane and the endothelium, with
      thickening of Descemet membrane, loss of barrier function, and increased corneal
      hydration, although secondary effects occur throughout all layers. Multiple
      chromosomal loci and, more recently, causal genetic mutations have been
      identified for this complex disorder, including in TCF8, SLC4A11, LOXHD1, and
      AGBL1. A trinucleotide repeat in TCF4 correlates strongly with disease status and
      interacts in common pathways with previously identified genes. Dysregulation of
      pathways involving oxidative stress and apoptosis, epithelial-to-mesenchymal
      transition, microRNA, mitochondrial genes, and unfolded protein response has been
      implicated in FCD pathogenesis. 

PMID- 26310152
TI  - Molecular Pathogenesis of Corneal Dystrophies: Schnyder Dystrophy and Granular
      Corneal Dystrophy type 2.
AB  - The International Committee for Classification of Corneal Dystrophies (IC3D)
      provides updated data to ophthalmologists by incorporating traditional
      definitions of corneal dystrophies with new genetic, clinical, and pathologic
      information. Recent advances in the genetics of corneal dystrophies facilitate
      more precise classifications and elucidate each classification's molecular
      mechanisms. Unfortunately, the molecular mechanisms and underlying pathogenic
      mechanisms have remained obscure, with the exception of Schnyder corneal
      dystrophy (CD), granular CD type 2 (GCD2), and Fuch's endothelial CD. Here, we
      review the pathogenesis of Schnyder CD and GCD2. 

PMID- 26310153
TI  - Overview of the Lens.
AB  - In order to accomplish its function of transmitting and focusing light, the
      crystalline lens of the vertebrate eye has evolved a unique cellular structure
      and protein complement. These distinct adaptations have provided a rich source of
      scientific discovery ranging from biochemistry and genetics to optics and
      physics. In addition, because of these adaptations, lens cells persist for the
      lifetime of an organism, providing an excellent model of the aging process. The
      chapters dealing with the lens will demonstrate how the different aspects of lens
      biology and biochemistry combine in this singular refractive organ to accomplish
      its critical role in the visual system. 

PMID- 26310154
TI  - Lens Development and Crystallin Gene Expression.
AB  - The eye and lens represent excellent models to understand embryonic development
      at cellular and molecular levels. Initial 3D formation of the eye depends on a
      reciprocal invagination of the lens placode/optic vesicle to form the eye
      primordium, i.e., the optic cup partially surrounding the lens vesicle.
      Subsequently, the anterior part of the lens vesicle gives rise to the lens
      epithelium, while the posterior cells of the lens vesicle differentiate into
      highly elongated lens fibers. Lens fiber differentiation involves cytoskeletal
      rearrangements, cellular elongation, accumulation of crystallin proteins,
      production of extracellular matrix for the lens capsule, and degradation of
      organelles. This chapter summarizes recent advances in lens development and
      provides insights into the regulatory mechanisms and differentiation at the level
      of chromatin structure and dynamics, the emerging field of noncoding RNAs, and
      novel strategies to fill the gaps in our understanding of lens development. 

PMID- 26310156
TI  - Molecular Genetics of Cataract.
AB  - Lens opacities or cataract(s) represent a universally important cause of visual
      impairment and blindness. Typically, cataract is acquired with aging as a complex
      disorder involving environmental and genetic risk factors. Cataract may also be
      inherited with an early onset either in association with other ocular and/or
      systemic abnormalities or as an isolated lens phenotype. Here we briefly review
      recent advances in gene discovery for inherited and age-related forms of cataract
      that are providing new insights into lens development and aging. 

PMID- 26310158
TI  - Scleral Mechanisms Underlying Ocular Growth and Myopia.
AB  - In the regulation of ocular growth, scleral events critically determine eye size
      and thus the refractive status of the eye. Increased scleral matrix remodeling
      can lead to exaggerated eye growth causing myopia and additionally increased risk
      of ocular pathological complications. Thus, therapies targeting these changes in
      sclera hold potential to limit such complications since sclera represents a
      relatively safe and accessible drug target. Understanding the scleral molecular
      mechanisms underlying ocular growth is essential to identifying plausible
      therapeutic targets in the sclera. This section provides a brief update on
      molecular studies that pertain to the sclera in the context of ocular growth
      regulation and myopia. 

PMID- 26310157
TI  - RPE and Choroid Mechanisms Underlying Ocular Growth and Myopia.
AB  - Myopia is the most common type of refractive errors and one of the world's
      leading causes of blindness. Visual manipulations in animal models have provided
      convincing evidence for the role of environmental factors in myopia development.
      These models along with in vitro studies have provided important insights into
      underlying mechanisms. The key locations of the retinal pigment epithelium (RPE)
      and choroid make them plausible conduits for relaying growth regulatory signals
      originating in the retina to the sclera, which ultimately determines eye size and
      shape. Identifying the key signal molecules and their targets may lead to the
      development of new myopia control treatments. This section summarizes findings
      implicating the RPE and choroid in myopia development. For RPE and/or choroid,
      changes in morphology, activity of ion channels/transporters, as well as in gene
      and protein expression, have been linked to altered eye growth. Both tissues thus
      represent potential targets for novel therapies for myopia. 

PMID- 26310155
TI  - Lens Biology and Biochemistry.
AB  - The primary function of the lens resides in its transparency and ability to focus
      light on the retina. These require both that the lens cells contain high
      concentrations of densely packed lens crystallins to maintain a refractive index
      constant over distances approximating the wavelength of the light to be
      transmitted, and a specific arrangement of anterior epithelial cells and arcuate
      fiber cells lacking organelles in the nucleus to avoid blocking transmission of
      light. Because cells in the lens nucleus have shed their organelles, lens
      crystallins have to last for the lifetime of the organism, and are specifically
      adapted to this function. The lens crystallins comprise two major families: the
      betagamma-crystallins are among the most stable proteins known and the alpha
      crystallins, which have a chaperone-like function. Other proteins and metabolic
      activities of the lens are primarily organized to protect the crystallins from
      damage over time and to maintain homeostasis of the lens cells. Membrane protein
      channels maintain osmotic and ionic balance across the lens, while the lens
      cytoskeleton provides for the specific shape of the lens cells, especially the
      fiber cells of the nucleus. Perhaps most importantly, a large part of the
      metabolic activity in the lens is directed toward maintaining a reduced state,
      which shelters the lens crystallins and other cellular components from damage
      from UV light and oxidative stress. Finally, the energy requirements of the lens
      are met largely by glycolysis and the pentose phosphate pathway, perhaps in
      response to the avascular nature of the lens. Together, all these systems
      cooperate to maintain lens transparency over time. 

PMID- 26310160
TI  - Genetics of Refraction and Myopia.
AB  - Both genetic and environmental factors play roles in the development of
      refractive errors. Identification of genes involved in refractive errors may help
      in elucidating the underlying molecular mechanism related to both genetic defects
      and environmental pressure. Recent development of techniques for genome wide
      analysis provides unique opportunity in dissecting the genetic basis related to
      refractive errors. This chapter tries to give a brief overview on the recent
      progress of genetic study of refractive errors, especially myopia. 

PMID- 26310159
TI  - Molecular and Biochemical Aspects of the Retina on Refraction.
AB  - Mutant mouse models with specific visual pathway defects offer an advantage to
      comprehensively investigate the role of specific pathways/neurons involved in
      refractive development. In this review, we will focus on recent studies using
      mouse models that have provided insight into retinal pathways and
      neurotransmitters controlling refractive development. Specifically, we will
      examine the contributions of rod and cone photoreceptors and the ON and OFF
      retinal pathways to visually driven eye growth with emphasis on dopaminergic
      mechanisms. 

PMID- 26310162
TI  - Intraocular Pressure and the Mechanisms Involved in Resistance of the Aqueous
      Humor Flow in the Trabecular Meshwork Outflow Pathways.
AB  - Intraocular pressure (IOP), the critical risk factor for glaucoma, is generated
      and maintained by the aqueous humor circulation system. Aqueous humor is secreted
      from the epithelial layers of the ciliary body and exits the eye through the
      trabecular meshwork or the uveoscleral outflow pathways. IOP builds up in
      response to a resistance to aqueous humor flow in the trabecular outflow
      pathways. The trabecular outflow 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 this region
      is lowered through the relaxation of contractile myofibroblast-like cells in
      trabecular meshwork and the adjacent scleral spur, or the contraction of the
      ciliary muscle. In primary open-angle glaucoma, the most frequent form of
      glaucoma, outflow resistance of the inner wall region is typically higher than
      normal. There is evidence that the increase in resistance is related to
      characteristic biological changes in the resident cells of the JCT, which more
      and more acquire the structural and functional characteristics of contractile
      myofibroblasts. The changes involve an augmentation of their actin cytoskeleton
      and of their surrounding fibrillary extracellular matrix, which connects to JCT
      cells via integrins. This scenario leads to an overall stiffening of the inner
      wall region, and is modulated by transforming growth factor-beta/connective
      tissue growth factor signaling. Essentially comparable changes appear to occur in
      SC endothelial cells. Stiffening of JCT and SC cells is very likely a critical
      causative factor for the increase in trabecular outflow resistance in POAG. 

PMID- 26310161
TI  - Molecular Genetic Advances in Uveitis.
AB  - Uveitis is usually considered as an intraocular inflammation characterized by
      variety of clinical features. Behcet's disease (BD), Vogt-Koyanagi-Harada (VKH)
      syndrome, acute anterior uveitis (AAU), and birdshot chorioretinopathy (BCR) are
      examples of noninfectious forms of uveitis. Although the precise pathogenesis
      remains unclear, accumulating evidence shows that complex genetic backgrounds
      coupled with an aberrant immune response may be implicated in the development of
      uveitis. The complement and pattern recognition systems are both important
      factors of the innate immune system and are involved in the pathogenesis of
      uveitis. Copy number variants (CNVs) of complement component 4 have been found to
      be associated with BD and VKH syndrome, but not with AAU. Several CNVs and gene
      polymorphisms of toll-like receptors were found to be associated with BD.
      Leukocytes are an important part of the adaptive immune system and various
      molecules on these cells play an important role in the development of uveitis.
      Genes encoding for human leukocyte antigens (HLAs) have been shown to be
      associated with certain uveitis entities, including BD (HLA-B51), VKH syndrome
      (HLA-DR4, DRB1/DQA1), AAU (HLA-B27), and BCR (HLA-A29). Genome wide association
      studies showed that the IL-23R locus was a shared risk factor for multiple
      uveitis entities including BD, AAU, and VKH syndrome. In addition, various other
      non-HLA genes are also associated with BD or VKH syndrome, such as IL-10, STAT4,
      STAT3, and UBAC2. These studies support the hypothesis that genetic factors play
      a key role in the pathogenesis of uveitis. 

PMID- 26310163
TI  - Glaucoma Genes and Mechanisms.
AB  - Genetic studies have yielded important genes contributing to both early-onset and
      adult-onset forms of glaucoma. The proteins encoded by the current collection of
      glaucoma genes participate in a broad range of cellular processes and biological
      systems. Approximately half the glaucoma-related genes function in the
      extracellular matrix, however proteins involved in cytokine signaling, lipid
      metabolism, membrane biology, regulation of cell division, autophagy, and ocular
      development also contribute to the disease pathogenesis. While the function of
      these proteins in health and disease are not completely understood, recent
      studies are providing insight into underlying disease mechanisms, a critical step
      toward the development of gene-based therapies. In this review, genes known to
      cause early-onset glaucoma or contribute to adult-onset glaucoma are organized
      according to the cell processes or biological systems that are impacted by the
      function of the disease-related protein product. 

PMID- 26310164
TI  - Neuroinflammation in Glaucoma and Optic Nerve Damage.
AB  - Glaucoma is a group of optic neuropathies characterized by the degeneration of
      retinal ganglion cell axons and somas, ultimately preventing light signals in the
      retina from reaching the brain. Glaucoma is a leading cause of blindness in the
      world, and treatment options for patients remain limited and minimally
      efficacious. A number of mechanisms have been linked to glaucomatous
      pathophysiology. A leading role is now attributed to neuroinflammatory conditions
      generated by the resident innate immune cells in the optic nerve and retina.
      Since the eye is immune privileged, the adaptation of these innate immune cells,
      termed glia, is crucial following trauma. In this chapter, we discuss the
      mechanisms associated with normal glial function in a healthy eye, and how
      changes in glial activation can contribute to the process of glaucomatous
      neurodegeneration in both the optic nerve and retina. 

PMID- 26310165
TI  - What Animal Models Can Tell Us About Glaucoma.
AB  - Well defined animal models facilitate the study of ocular diseases. Each model
      brings a unique perspective to the understanding of the disease process, and in
      some cases, the models are critical to the development of therapeutic approaches
      for treatments. This is especially the case for glaucoma. Glaucoma is a family of
      diseases that can be caused by very different biological processes. The one thing
      in common is the end result, the loss of retinal ganglion cells and blindness. In
      this review, we will attempt to relate the findings from a number of animal
      models to specific types of glaucoma, emphasizing the contributions that each of
      the models makes to our overall understanding of the complex collection of
      diseases we call glaucoma. 

PMID- 26310166
TI  - Introduction to the Retina.
AB  - Here, we briefly introduce and survey the retina including terminology and naming
      conventions. We consider anatomical structures of the retina including gross and
      microscopic anatomy of the fundus, layers of the retina, retinal cell types, and
      neuronal wiring of the retina. We discuss briefly biochemistry of the visual
      transduction cascade and the Vitamin A cycle. We introduce physiological
      processes including outer segment disk shedding and origins of electrical signals
      detected by the electroretinogram. This sets the stage for a more in-depth look
      at specific aspects of retinal structure and function in subsequent sections in
      this chapter. 

PMID- 26310168
TI  - Insights into the Molecular Properties of ABCA4 and Its Role in the Visual Cycle
      and Stargardt Disease.
AB  - ABCA4 is a member of the A-subfamily of ATP-binding cassette (ABC) transporters
      localized in rod and cone outer segment disc membranes. Over 800 mutations in
      ABCA4 are now known to cause Stargardt macular degeneration and related retinal
      degenerative diseases. Biochemical studies have shown that ABCA4 transports or
      flips the 11-cis and all-trans isomers of N-retinylidene-phosphatidylethanolamine
      across disc membranes, thereby facilitating the removal of retinal from disc
      membranes through the visual cycle and preventing the accumulation of potentially
      toxic bisretinoid compounds in photoreceptor and retinal pigment epithelial
      cells. This chapter summarizes studies which have led to our understanding of the
      role of ABCA4 in the visual cycle and Stargardt disease. 

PMID- 26310167
TI  - Development of the Vertebrate Eye and Retina.
AB  - The mature, functional, and healthy eye is generated by the coordinated
      regulatory interaction of numerous and diverse developing tissues. The neural
      retina of the eye must undergo the neurogenesis of multiple retinal cell types in
      the correct ratios and spatial patterns. This chapter provides an overview of
      retinal development, and includes a summary of the process of eye organogenesis,
      a discussion of major principles of retinal neurogenesis, and describes some of
      the key molecular factors critical for retinal development. Defects in many of
      these factors underlie diseases of the eye, and an understanding of the process
      of retinal development will be critical for successful future applications of
      regenerative therapies for eye disease. 

PMID- 26310169
TI  - A History of the Classical Visual Cycle.
AB  - The visual cycle, the biochemical process by which the light-sensitive isomer of
      vitamin A is continually recycled, is crucial to vision in a healthy eye. More
      than 150 years of research into this remarkable biochemical process has given
      invaluable understanding in debilitating visual diseases that impact thousands of
      individuals worldwide, many of them children. The visual cycle spans
      photoreceptor cells in the retina and the underlying retinal pigment epithelium
      (RPE) and requires a protein called RPE65 for its function. In many ways, RPE65
      is the capstone to the cyclical processing of vitamin A in the eye, and the
      discovery of this retinol isomerase helped fill a critical gap in the
      understanding of retinoid processing in vision. This chapter will focus on the
      history of visual cycle research, from the first experiments well over a century
      ago to the discovery of RPE65. Because of the undeniable importance of RPE65 in
      the visual cycle, this chapter will also focus on the protein structure and
      mechanism by which it converts light-insensitive all-trans-vitamin A to light
      sensitive 11-cis-vitamin A for continued visual function. Finally, this chapter
      will briefly discuss RPE65 and its known disease associations in the clinical
      setting. Thanks to the efforts of researchers for well over a century in studying
      the visual cycle, the medical community is now poised to make significant gains
      in the treatment of blindness. 

PMID- 26310170
TI  - A2E and Lipofuscin.
AB  - Lipofuscin is highly fluorescent material, formed in several tissues but best
      studied in the eye. The accumulation of lipofuscin in the retinal pigment
      epithelium (RPE) is a hallmark of aging in the eye and has been implicated in
      various retinal degenerations, including age-related macular degeneration. The
      bis-retinoid N-retinyl-N-retinylidene ethanolamine (A2E), formed from retinal,
      has been identified as a byproduct of the visual cycle, and numerous in vitro
      studies have found toxicity associated with this compound. The compound is known
      to accumulate in the RPE with age and was the first identified compound extracted
      from lipofuscin. Our studies have correlated the distribution of lipofuscin and
      A2E across the human and mouse RPE. Lipofuscin fluorescence was imaged in the RPE
      from human donors of various ages and from assorted mouse models. The spatial
      distribution of A2E was determined using matrix-assisted laser desorption
      ionization imaging mass spectrometry on both flat-mounted and transversally
      sectioned RPE tissue. Our data support the clinical observations in humans of
      strong RPE fluorescence, increasing with age, in the central area of the RPE.
      However, there was no correlation between the distribution of A2E and lipofuscin,
      as the levels of A2E were highest in the far periphery and decreased toward the
      central region. Interestingly, in all the mouse models, A2E distribution and
      lipofuscin fluorescence correlate well. These data demonstrate that the
      accumulation of A2E is not responsible for the increase in lipofuscin
      fluorescence observed in the central RPE with aging in humans. 

PMID- 26310171
TI  - Cone Health and Retinoids.
AB  - Cones are photoreceptor cells used for bright light and color vision. Retinoids
      are vitamin A derivatives, one of which is the 11-cis aldehyde form that serves
      as the chromophore for both cone and rod visual pigments. In the visual disease,
      Type 2 Leber congenital amaurosis (LCA2), 11-cis-retinal generation is inhibited
      or abolished. Work by others has shown that patients with LCA2 have symptoms
      consistent with degenerating cones. In mouse models for LCA2, early cone
      degeneration is readily apparent: cone opsins and other proteins associated with
      the outer segment are delocalized and cell numbers decline rapidly within the
      first month. Rods would appear normal morphologically and functionally, if not
      for the absence of chromophore. Supplementation of mouse models of LCA2 with cis
      retinoids has been shown to slow loss of cone photoreceptor cells if mice were
      maintained in darkness. Thus, 11-cis-retinal appears not only to have a role in
      the light response reaction but also to promote proper trafficking of the cone
      opsins and maintain viable cones. 

PMID- 26310172
TI  - Retinoid Processing in Induced Pluripotent Stem Cell-Derived Retinal Pigment
      Epithelium Cultures.
AB  - Stem cell therapy for retinal degenerative diseases such as age-related macular
      degeneration is a promising clinical option for the replacement of photoreceptors
      and retinal pigment epithelium (RPE). Induced pluripotent stem cell technology
      has emerged as a viable potential source of cells for transplantation in retinal
      degenerative disorders. Induced pluripotent stem cells have been used to derive
      RPE and have been tested for their functional behavior. These cells have the
      ability to express RPE-specific proteins and morphologically resemble native RPE.
      Induced pluripotent stem cell-derived RPE are also able to contribute to the
      visual cycle by their ability to metabolize all-trans retinol, a critical
      function of RPE in maintaining visual function. Advances in induced pluripotent
      stem cell technology will contribute to the development of clinical therapies for
      retinal degenerative diseases as well as provide a tool to understand the
      pathology of these disorders. 

PMID- 26310174
TI  - The Biology of Retinoblastoma.
AB  - Retinoblastoma, the most common primary intraocular cancer of childhood, is a
      malignancy arising in the developing retina. Tumor formation usually begins with
      mutation in both alleles of the retinoblastoma tumor suppressor gene RB1,
      followed by a series of other genetic alterations that correlate with the
      clinical stage and pathologic findings of the tumor. Analysis of sporadic and
      heritable retinoblastoma led to the development of Knudson's Two-Hit Hypothesis.
      The tumor suppressor RB1 gene codes for the retinoblastoma protein which is a key
      regulator of cellular replication via its binding to the E2F family of
      transcription factors and chromatin remodeling proteins. Studies of preclinical
      models of retinoblastoma in the form of transgenic mice and xenograft animal
      models have significantly contributed to the development of effective therapies
      for this disease. Research on retinoblastoma has paved the way toward
      understanding many of the mechanisms in cancer genetics. 

PMID- 26310173
TI  - Potential Role of Exercise in Retinal Health.
AB  - For many patients suffering vision loss due to retinal degeneration, the
      potential exists for therapeutic intervention to halt or delay disease
      progression. Proposed molecular, pharmacological, and surgical treatments are
      expensive and complicated. Finding low-cost interventions to sustain vision and
      thereby quality of life is vitally important. This chapter reviews findings from
      animal model and human subject studies indicating that physical exercise has
      direct, beneficial effects on regions of the central nervous system and is
      protective against neurodegenerative disease, including recent data from animal
      models showing similar effects for retina and vision. Potential local and
      systemic mechanistic pathways for exercise-induced retinal neuroprotection are
      discussed. 

PMID- 26310175
TI  - The 11-cis Retinal Origins of Lipofuscin in the Retina.
AB  - Lipofuscin is a fluorescent mixture of partially digested proteins and lipids
      that accumulates with age in the lysosomal compartment of the retinal pigment
      epithelium (RPE) of the eye. Because it has been found to have significant
      cytotoxic potential, lipofuscin is thought to play a role in retinal degeneration
      diseases including age-related macular degeneration and Stargardt disease, a form
      of juvenile macular degeneration. The only known components of lipofuscin are bis
      retinoids, the condensation products of two molecules of retinal. The bulk of
      lipofuscin is thought to originate in the rod photoreceptor outer segments as a
      by-product of reactions involving the retinal chromophore of rhodopsin. 11-cis
      retinal flows from the RPE into the rod outer segments, where it combines with
      opsin to form rhodopsin; all-trans retinal is released into the rod outer
      segments by photoactivated rhodopsin following its excitation by light. Both 11
      cis and all-trans retinal can generate lipofuscin-like fluorophores and bis
      retinoids when added to rod outer segment membranes. The levels of lipofuscin
      precursor fluorophores present in the outer segments of dark-adapted rods are
      similar in cyclic-light- and dark-reared mice, as are the levels of accumulated
      lipofuscin in the RPE. Because the retinol dehydrogenase enzyme present in rod
      outer segments can reduce all-trans but not 11-cis retinal, lipofuscin precursors
      are more likely to form from 11-cis than all-trans retinal, even under cyclic
      light conditions. Thus, 11-cis retinal may be the primary source of lipofuscin in
      the retina. 

PMID- 26310176
TI  - Preface. Molecular Biology of Eye Disease.

PMID- 26310177
TI  - Hepatic IGF1 DNA methylation is influenced by gender but not by intrauterine
      growth restriction in the young lamb.
AB  - Intrauterine growth restriction (IUGR) and postnatal catch-up growth confer an
      increased risk of adult-onset disease. Overnourishment of adolescent ewes
      generates IUGR in ~ 50% of lambs, which subsequently exhibit increased fractional
      growth rates. We investigated putative epigenetic changes underlying this early
      postnatal phenotype by quantifying gene-specific methylation at cytosine:guanine
      (CpG) dinucleotides. Hepatic DNA/RNA was extracted from IUGR [eight male (M)/nine
      female (F)] and normal birth weight (12 M/9 F) lambs. Polymerase chain reaction
      was performed using primers targeting CpG islands in 10 genes: insulin, growth
      hormone, insulin-like growth factor (IGF)1, IGF2, H19, insulin receptor, growth
      hormone receptor, IGF receptors 1 and 2, and the glucocorticoid receptor. Using
      pyrosequencing, methylation status was determined by quantifying cytosine:thymine
      ratios at 57 CpG sites. Messenger RNA (mRNA) expression of IGF system genes and
      plasma IGF1/insulin were determined. DNA methylation was independent of IUGR
      status but sexual dimorphism in IGF1 methylation was evident (MF (both P<0.001).
      IGF1 mRNA expression correlated negatively with IGF1 methylation (r=-0.507,
      P=0.002) and positively with plasma IGF1 (r=0.884, P<0.001). Carcass and empty
      body weights were greater in males (P=0.002-0.014) and this gender difference in
      early body conformation was mirrored by sexual dimorphism in hepatic IGF1 DNA
      methylation, mRNA expression and plasma IGF1 concentrations.

PMID- 26310178
TI  - [Host defense and oxidative stress signaling in bacterial infection?].
AB  - Nitric oxide (NO) and reactive oxygen species (ROS) produced during infection are
      involved critically in host defense mechanisms. It is quite important to
      physiologically regulate ROS, such as superoxide, and NO. These reactive species
      produced in excess may cause oxidative damage of biological molecules. An
      important cytoprotective and antimicrobial function of NO and ROS is mediated by
      induction of heme oxygenase (HO)-1. The signaling mechanism of this HO-1
      induction has remained unclear, however. We discovered in 2007 a unique second
      messenger, 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP), that
      mediates electrophilic signal transduction during oxidative stress and other
      cellular redox signaling in general. 8-Nitro-cGMP is formed via guanine nitration
      with NO and ROS, and in fact, NO-dependent 8-nitro-cGMP formation and HO-1
      induction were identified in Salmonella-infected mice. HO-1 induction was
      regulated solely by 8-nitro-cGMP formed in cells, and more important, its potent
      anti-apoptotic function was evident in such a Salmonella infection. 8-Nitro-cGMP
      has a potent cytoprotective function, of which signaling appears to be mediated
      via protein sulfhydryls to generate a post-translational modification called
      protein S-guanylation. 8-Nitro-cGMP specifically S-guanylates Keap1, a negative
      regulator of transcription factor Nrf2, which in turn up-regulates transcription
      of HO-1. Our recent study revealed that the autophagy might be involved in the 8
      nitro-cGMP-dependent antimicrobial effect. The 8-nitro-cGMP signaling was also
      found to be regulated by reactive sulfur species that have superior antioxidant
      activity and unique signaling function. This review will discuss a new paradigm
      of the host defense that operates via formation of a unique cell signaling
      molecule, 8-nitro-cGMP, during microbial infections. 

PMID- 26310179
TI  - [Structure and function of the bacterial flagellar type III protein export system
      in Salmonella?].
AB  - The bacterial flagellum is a filamentous organelle that propels the bacterial
      cell body in liquid media. For construction of the bacterial flagellum beyond the
      cytoplasmic membrane, flagellar component proteins are transported by its
      specific protein export apparatus from the cytoplasm to the distal end of the
      growing flagellar structure. The flagellar export apparatus consists of a
      transmembrane export gate complex and a cytoplasmic ATPase ring complex.
      Flagellar substrate-specific chaperones bind to their cognate substrates in the
      cytoplasm and escort the substrates to the docking platform of the export gate.
      The export apparatus utilizes ATP and proton motive force across the cytoplasmic
      membrane as the energy sources to drive protein export and coordinates protein
      export with assembly by ordered export of substrates to parallel with their order
      of assembly. In this review, we summarize our current understanding of the
      structure and function of the flagellar protein export system in Salmonella
      enterica serovar Typhimurium. 

PMID- 26310180
TI  - Demarcation of secondary hyperalgesia zones: Punctate stimulation pressure
      matters.
AB  - BACKGROUND: Secondary hyperalgesia is increased sensitivity in normal tissue near
      an injury, and it is a measure of central sensitization reflecting injury-related
      effects on the CNS. Secondary hyperalgesia areas (SHAs), usually assessed by
      polyamide monofilaments, are important outcomes in studies of analgesic drug
      effects in humans. However, since the methods applied in demarcating the
      secondary hyperalgesia zone seem inconsistent across studies, we examined the
      effect of a standardized approach upon the measurement of SHA following a first
      degree burn injury (BI). NEW METHOD: The study was a two-observer, test-retest
      study with the two sessions separated by 6wk. An observer-blinded design adjusted
      to examine day-to-day and observer-to-observer variability in SHA was used. In 23
      healthy volunteers (12 females/11 males) a BI was induced by a contact thermode
      (47.0 degrees C, 420s, 2.5*5.0cm(2)). The SHA, demarcated by polyamide
      monofilaments (bending force: 0.2, 69 and 2569mN) and a "weighted-pin" stimulator
      (512mN), were assessed 45 to 75min after each BI. RESULTS: A random effect,
      linear mixed model demonstrated a logarithmic correlation between elicited skin
      pressures (mN/mm(2)) and the SHAs (P<0.0001). No day-to-day or observer-to
      observer differences in SHAs were observed. Intraclass correlation coefficients,
      in the range of 0.51 to 0.84, indicated a moderate to almost perfect reliability
      between observers. COMPARISON WITH EXISTING METHODS: No standardized approach in
      SHA-assessment has hitherto been presented. CONCLUSIONS: This is the first study
      to demonstrate that demarcation of secondary hyperalgesia zones depends on the
      developed pressure of the punctate stimulator used.

PMID- 26310181
TI  - Real time adenosine fluctuations detected with fast-scan cyclic voltammetry in
      the rat striatum and motor cortex.
AB  - BACKGROUND: Adenosine serves many functions within the CNS, including inhibitory
      and excitatory control of neurotransmission. The understanding of adenosine
      dynamics in the brain is of fundamental importance. The goal of the present study
      was to explore subsecond adenosine fluctuations in the rat brain in vivo. METHOD:
      Long Evans rats were anesthetized and a carbon fiber electrode was positioned in
      the motor cortex or dorsal striatum. Real time electrochemical recordings were
      made at the carbon fiber electrodes every 100ms by applying a triangular waveform
      (-0.4 to +1.5V, 400V/s). Adenosine spikes were identified by the background
      subtracted cyclic voltammogram. RESULTS: The frequency of detected adenosine
      spikes was relatively stable in both tested regions, and the time intervals
      between spikes were regular and lasted from 1 to 5s within an animal. Spike
      frequency ranged from 0.5 to 1.5Hz in both the motor cortex and the dorsal
      striatum. Average spike amplitudes were 85+/-11 and 66+/-7nM for the motor cortex
      and the dorsal striatum, respectively. COMPARISON WITH EXISTING METHODS: The
      current study established that adenosine signaling can operate on a fast time
      scale (within seconds) to modulate brain functions. CONCLUSIONS: This finding
      suggests that spontaneous adenosine release may play a fast, dynamic role in
      regulating an organism's response to external events. Therefore, adenosine
      transmission in the brain may have characteristics similar to those of classical
      neurotransmitters, such as dopamine and norepinephrine.

PMID- 26310182
TI  - Association between adherence, treatment satisfaction and illness perception in
      hypertensive patients.
AB  - The relationship between adherence to antihypertension medications, treatment
      satisfaction and illness perception has not been studied so far. The primary
      objective of this study was to examine the association between adherence to
      medication, treatment satisfaction and illness perception in Lebanese
      hypertensive patients. The relation between medication adherence and blood
      pressure (BP) control was also assessed. In this cross-sectional study, patients
      were recruited from the physician's practice offices and community pharmacies in
      Beirut. Patients who had been treated for hypertension for at least 3 months were
      invited to participate in the study; they completed three questionnaires: the 8
      item Morisky Medication Adherence Scale (MMAS-8), the Treatment Satisfaction
      Questionnaire for Medication (TSQM-4) and the Brief Illness Perception
      Questionnaire (BIPQ). BP was also measured and recorded. A total of 117 subjects
      were included, of whom 29.1% had poor adherence to their antihypertension
      treatment (MMAS-8 scores<6). The odds of having well-controlled hypertension was
      3.5 times higher in patients with high adherence compared with patients with poor
      adherence (P=0.010). Treatment satisfaction was significantly greater in patients
      with good adherence (P<0.001). Neither socio-demographic, disease- nor drug
      related characteristics of the participants were significantly associated with
      medication adherence. As for illness perception, even though the mean BIPQ score
      of adherent participants was lower than the mean score of non-adherent
      participants, this difference did not reach statistical significance. In
      conclusion, treatment satisfaction was found to be a predictor of adherence.
      Studies are needed to determine whether interventions to increase satisfaction
      can improve adherence and BP control. 

PMID- 26310183
TI  - Plasma renin and cardiovascular responses to the cold pressor test differ in
      black and white populations: The SABPA study.
AB  - Low plasma renin levels and augmented cardiovascular reactivity to stress are
      common in blacks and have been linked to the development of hypertension in this
      population. We (i) compared cardiovascular and plasma renin reactivity to a cold
      pressor test between a black and white population; and (ii) investigated the
      associations between cardiovascular and plasma renin reactivity within the black
      and white populations. Our population consisted of 153 black and 188 white men
      and women (age range, 20-65 years). We measured blood pressure (BP), heart rate
      (HR), stroke volume (SV), total peripheral resistance (TPR), Windkessel arterial
      compliance, and determined plasma renin levels at rest and during the cold
      pressor test. Reactivity was calculated for each participant as the percentage
      change from the resting value. We found lower renin and elevated BP in blacks
      compared with whites at rest and during stress (both, P<0.001). During stress, HR
      increased more in blacks (P<0.001), whereas SV (P<0.001) and arterial compliance
      (P=0.013) decreased more in blacks compared with whites. TPR reactivity was
      positively associated with renin reactivity in blacks only (beta=0.17; P=0.041),
      while in whites diastolic BP reactivity was positively associated with renin
      reactivity (beta=0.21; P=0.005). Although blacks had suppressed renin levels at
      rest and during acute stress, vascular resistance reactivity associated
      positively with renin reactivity only in the black population. These results
      suggest that low renin levels in blacks during rest and stress are linked to
      increased peripheral vascular responses to stress, which may contribute to
      elevated BP in blacks. 

PMID- 26310184
TI  - Plasma renalase concentration before and after radiofrequency renal denervation
      in patients with resistant hypertension.

PMID- 26310185
TI  - Risks and predictors of mild diastolic dysfunction among middle-aged and aged
      women: a population-based cohort study.
AB  - We sought to determine the predictors of primary episodes of mild diastolic
      dysfunction (DD) in a cohort of women aged >45 years, who had >2 echocardiography
      from 2009 to 2012. Patients were excluded if they had prior diagnosis of coronary
      artery disease, heart failure, valvular heart disease or echocardiographic
      evidence of DD. Mild DD was defined as: left ventricular ejection fraction>50%,
      E/A ratio<0.75, and E/e'?8. Out of the total 758 subjects (age 64.15+/-7.24
      years), 109 (14.3%) had developed mild DD, during a mean followup period of 3
      years. Independent predictors of mild DD included: age (P<0.001), history of
      hypertension (P=0.022), body mass index (BMI) (P<0.001), total triglycerides (TG)
      (P=0.016), inter ventricular septal thickness (P=0.015) and brachial-ankle pulse
      wave velocity (baPWV) ?16 m s(-1) (P<0.001). E/A ratio was inversely associated
      with age (r=-0.337, P<0.001), baPWV (r=-0.359, P<0.001), BMI (r=-0.290, P<0.001)
      and TG (r=-0.255, P<0.001). The Area Under roc Curve for a linear combination of
      age, BMI, baPWV and TG was 0.738 (95% confidence interval: 0.683-0.804, P<0.001),
      which was superior to any of the variables taken alone. In summary, many middle
      aged or elderly women may develop mild DD within a relatively short period of 3
      years. Several subclinical abnormalities and cardiovascular parameters were
      determined to contribute to the onset of DD. 

PMID- 26310186
TI  - High prevalence, low awareness, treatment and control rates of hypertension in
      Guinea: results from a population-based STEPS survey.
AB  - Hypertension is a major and fast-growing public health problem in Africa. We
      determined the prevalence of hypertension and assessed the levels of awareness,
      treatment and control in Guinea. A cross-sectional study based on a stratified
      cluster random sampling was conducted. In all, 2491 adults (1351 women) aged 15
      64 years were selected and screened during September-December 2009. Hypertension
      (systolic (and/or diastolic) blood pressure ?140 (90) mm Hg or use of
      antihypertensive medications) and diabetes mellitus (fasting capillary glucose
      ?110  mg dl(-1) or use of antidiabetic medications) were determined. Logistic
      regressions were used to investigate the determinants of hypertension. The mean
      body mass index was 22.4  kg m(-2) (s.d.=4.5). The prevalence of hypertension and
      diabetes was, respectively, 29.9% (95% confidence interval (CI) 29.8-30.0) and
      3.5% (95%CI 3.4-3.5). The prevalence of hypertension was 29.4% (29.3-29.5) in men
      and 30.4% (30.4-30.6) in women. The prevalence was 62.5% in the 44-64 years age
      group. Overall, 75.8% of hypertensive participants were undetected before the
      survey and 34.9% of those aware of their hypertensive status were receiving
      treatment, of whom 16.3% were at target control levels. Age, education, diabetes
      and obesity were the main factors associated with hypertension. There was a high
      prevalence of hypertension among the adults in Guinea, but with low awareness,
      treatment and control rates. Urgent response is needed in the form of integrated
      and comprehensive action targeting major non-communicable diseases in the
      country.

PMID- 26310187
TI  - Four to seven random casual urine specimens are sufficient to estimate 24-h
      urinary sodium/potassium ratio in individuals with high blood pressure.
AB  - This study was done to clarify the optimal number and type of casual urine
      specimens required to estimate urinary sodium/potassium (Na/K) ratio in
      individuals with high blood pressure. A total of 74 individuals with high blood
      pressure, 43 treated and 31 untreated, were recruited from the Japanese general
      population. Urinary sodium, potassium and Na/K ratio were measured in both casual
      urine samples and 7-day 24-h urine samples and then analyzed by correlation and
      Bland-Altman analyses. Mean Na/K ratio from random casual urine samples on four
      or more days strongly correlated with the Na/K ratio of 7-day 24-h urine (r=0.80
      0.87), which was similar to the correlation between 1 and 2-day 24-h urine and 7
      day 24-h urine (r=0.75-0.89). The agreement quality for Na/K ratio of seven
      random casual urine for estimating the Na/K ratio of 7-day 24-h urine was good
      (bias: -0.26, limits of agreements: -1.53-1.01), and it was similar to that of 2
      day 24-h urine for estimating 7-day 24-h values (bias: 0.07, limits of agreement:
      -1.03 to 1.18). Stratified analyses comparing individuals using antihypertensive
      medication and individuals not using antihypertensive medication showed similar
      results. Correlations of the means of casual urine sodium or potassium
      concentrations with 7-day 24-h sodium or potassium excretions were relatively
      weaker than those for Na/K ratio. The mean Na/K ratio of 4-7 random casual urine
      specimens on different days provides a good substitute for 1-2-day 24-h urinary
      Na/K ratio for individuals with high blood pressure. 

PMID- 26310188
TI  - New and Emerging Agents for the Treatment of Hemophilia: Focus on Extended Half
      Life Recombinant Clotting Proteins.
AB  - Hemophilia A and B are X-linked disorders caused by deficient or defective
      clotting factor VIII (FVIII) or IX factor (FIX) proteins, and characterized by
      spontaneous or traumatic bleeding into joints and muscles. Previous use of plasma
      and plasma-derived clotting factors that lacked appropriate viral inactivation
      steps in manufacturing led to significant morbidity associated with transfusion
      transmitted HIV and hepatitis C virus (HCV). The development of recombinant
      proteins revolutionized their treatment, and, with no new HIV or HCV infection
      via clotting proteins for nearly 30 years, greatly improved their lifespan, which
      now approaches that of the general population, and with the same risks for aging
      complications. Novel long-acting factor proteins are being licensed to extend
      FVIII and FIX half-life, thereby reducing infusion frequency and potentially
      bleed frequency and associated morbidity. Further, novel therapeutics which take
      advantage of new technologies, including siRNA, monoclonal antibody, and small
      peptide inhibition technologies, have the potential to simplify treatment and
      improve outcomes for those with inhibitors.

PMID- 26310190
TI  - Brexpiprazole: First Global Approval.
AB  - Brexpiprazole (Rexulti(r)) is an atypical antipsychotic that has been developed
      by Otsuka Pharmaceutical Co. Ltd and H. Lundbeck A/S as an oral treatment for
      several psychiatric disorders. Brexpiprazole is a novel serotonin-dopamine
      activity modulator that acts as a partial agonist of serotonin 1A (5-HT1A) and
      dopamine D2 receptors, as well as a potent antagonist of 5-HT2A receptors and
      noradrenergic alpha1B and alpha2C receptors. In July 2015, brexpiprazole received
      its first approval in the USA for use as an adjunctive treatment of major
      depressive disorder (MDD) and the treatment of schizophrenia. In several
      countries, brexpiprazole is in development for MDDs, schizophrenia, post
      traumatic stress disorder and agitation in patients with dementia of the
      Alzheimer's type. This article summarizes the milestones in the development of
      brexpiprazole leading to its first global approval in MDD and schizophrenia.

PMID- 26310191
TI  - Targeted intracellular accumulation of macrophage migration inhibitory factor in
      the reperfused heart mediates cardioprotection.
AB  - S-nitrosation of macrophage migration inhibitory factor (MIF) has been shown to
      be cytoprotective in myocardial ischaemia/reperfusion (I/R) injury. Since the
      exact mechanism of action is unknown, we here characterise the cardioprotective
      effects of targeted intracellular accumulation of MIF in myocardial I/R injury.
      We used different in vivo, ex vivo and in vitro models of myocardial I/R and
      hypoxia/reoxygenation (H/R) injury to determine MIF levels by immunoblots and
      ELISA in different phases of reperfusion and reoxygenation, respectively. We
      discovered a rapid decrease of cardiac MIF that was specific to the early phase
      of reperfusion. Posttranslational modification of MIF via S-nitrosation--proofed
      by a modified version of the Biotin Switch Assay--prevented this rapid decrease,
      leading to a targeted intracellular accumulation of MIF in the early phase of
      reperfusion. Intracellular MIF accumulation preserved the intracellular ability
      of MIF to reduce oxidative stress as shown by hydrogen peroxide and aconitase
      activity measurements. Infarct size measurements by TTC staining showed an
      overall enhanced cardioprotective effect of this protein by reduction of
      reperfusion injury. In summary, we have unravelled a novel mechanism of MIF
      mediated cardioprotection. Targeted intracellular accumulation of MIF by S
      nitrosation may offer a novel therapeutic approach in the treatment of myocardial
      I/R-injury.

PMID- 26310192
TI  - Who Uses the Internet as a Source of Nutrition and Dietary Information? An
      Australian Population Perspective.
AB  - BACKGROUND: The Internet contains a plethora of nutrition information. Health
      organizations are increasingly using the Internet to deliver population-wide
      health information and interventions. Effective interventions identify their
      target population and their needs; however, little is known about use of the
      Internet as a source of nutrition information. OBJECTIVE: The aim was to assess
      the change in prevalence and demographic characteristics of Western Australian
      adults accessing the Internet as a source of nutrition information and identify
      specific information needs. METHODS: Data were pooled from the Western Australian
      Department of Health's 3-yearly Nutrition Monitoring Survey Series telephone
      survey between 1995 and 2012 of 7044 participants aged 18 to 64 years. Outcome
      variables were the main sources of nutrition information used in the last year
      and yes/no responses to 4 suggestions to what would make it easier to eat a
      healthy diet. Sociodemographic variables were collected. RESULTS: The proportion
      of respondents using the Internet for nutrition information increased from <1% in
      1995-2001 to 9.1% in 2004 and 33.7% in 2012. Compared to 2004, logistic
      regression showed that the odds of using the Internet for this information
      increased significantly in 2009 (OR 2.84, 95% CI 2.07-3.88) and 2012 (OR 5.20,
      95% CI 3.86-7.02, P<.001). Respondents using the Internet as a source were more
      likely to be female (OR 1.30, 95% CI 1.05-1.60, P=.02), live in a metropolitan
      area (OR 1.26, 95% CI 1.03-1.54, P=.03), born in countries other than
      Australia/UK/Ireland (OR 1.41, 95% CI 1.07-1.85, P=.02), more educated
      (university: OR 2.46, 95% CI 1.77-3.42, P<.001), and were less likely to be older
      (55-64 years: OR 0.38, 95% CI 0.25-0.57, P<.001). The majority of respondents
      agreed the following information would assist them to make healthier choices:
      more ways to prepare healthy foods (72.0%, 95% CI 70.7-73.3), quicker ways to
      prepare healthy foods (79.0%, 95% CI 77.8-80.1), how to choose healthy foods
      (68.8%, 95% CI 67.5-70.1), and knowing more about cooking (54.7%, 95% CI 53.3
      56.1). Those using the Internet for nutrition information were more likely than
      nonusers to want to know quicker ways to prepare healthy foods (83.0% vs 78.1%,
      P=.005) and information on choosing healthy foods (76.3% vs 67.3%, P<.001).
      CONCLUSIONS: Use of the Internet as a main source of nutrition information has
      grown rapidly since 2004; one-third of Western Australian adults reported using
      the Internet for this purpose in 2012. Information on preparing healthy foods
      (ideas, quicker ways), choosing ingredients, and knowing more about cooking would
      make it easier to eat a healthy diet. For Internet users, emphasis should be on
      quicker ways and choosing ingredients. These finding have implications for policy
      makers and practitioners and suggest that traditional health promotion tactics
      should continue to be used to reach the broader population.

PMID- 26310193
TI  - Eating disorders in military and veteran men and women: A systematic review.
AB  - OBJECTIVE: Eating disorders (EDs) have serious consequences for psychological and
      physical health. They have high mortality rates and are among the most costly
      disorders to treat. However, EDs remain understudied in military and veteran
      populations. The aim of this review was to examine prevalence estimates and
      associated symptomatology of EDs among military and veteran men and women and to
      identify factors that may put these individuals at risk for the development of an
      ED for the purposes of improving detection, intervention, and treatment. METHOD:
      A thorough literature review was conducted using the databases PsycINFO and
      PubMed. All articles with a focus on EDs in military/veteran samples were
      considered. RESULTS: Studies reveal high prevalence estimates of EDs among
      military/veteran men and women. Unique features of military life may increase the
      risk for development of an ED, including: military sexual trauma, strict weight
      and physical fitness requirements, and combat exposure. A history of trauma was
      common in individuals diagnosed with an ED in military and veteran samples.
      DISCUSSION: The high rates of EDs among military and veteran samples underscore
      the importance of further research, as well as the importance of screening and
      intervention efforts, in these understudied populations.

PMID- 26310189
TI  - Pharmacotherapy for Status Epilepticus.
AB  - Status epilepticus (SE) represents the most severe form of epilepsy. It is one of
      the most common neurologic emergencies, with an incidence of up to 61 per 100,000
      per year and an estimated mortality of 20 %. Clinically, tonic-clonic convulsive
      SE is divided into four subsequent stages: early, established, refractory, and
      super-refractory. Pharmacotherapy of status epilepticus, especially of its later
      stages, represents an "evidence-free zone," due to a lack of high-quality,
      controlled trials to inform clinical decisions. This comprehensive narrative
      review focuses on the pharmacotherapy of SE, presented according to the four
      staged approach outlined above, and providing pharmacological properties and
      efficacy/safety data for each antiepileptic drug according to the strength of
      scientific evidence from the available literature. Data sources included MEDLINE
      and back-tracking of references in pertinent studies. Intravenous lorazepam or
      intramuscular midazolam effectively control early SE in approximately 63-73 % of
      patients. Despite a suboptimal safety profile, intravenous phenytoin or
      phenobarbital are widely used treatments for established SE; alternatives include
      valproate, levetiracetam, and lacosamide. Anesthetics are widely used in
      refractory and super-refractory SE, despite the current lack of trials in this
      field. Data on alternative treatments in the later stages are limited. Valproate
      and levetiracetam represent safe and effective alternatives to phenobarbital and
      phenytoin for treatment of established SE persisting despite first-line treatment
      with benzodiazepines. To date there are no class I data to support
      recommendations for most antiepileptic drugs for established, refractory, and
      super-refractory SE. Limiting the methodologic heterogeneity across studies is
      required and high-class randomized, controlled trials to inform clinicians about
      the best treatment in established and refractory status are needed.

PMID- 26310194
TI  - Aripiprazole for Tourette's syndrome: a systematic review and meta-analysis.
AB  - OBJECTIVE: To review the efficacy and safety of aripiprazole (ARI) for Tourette's
      syndrome (TS). METHODS: This review included randomized controlled trials (RCTs)
      of children and adolescents (6-18 years) with TS comparing ARI monotherapy with
      another monotherapies in relation to clinical improvement and adverse events.
      RESULTS: Six RCTs with a total of 528 subjects (ARI treatment group: n = 253;
      control group: n = 275) met the inclusion criteria. These included two RCTs (n =
      255) that compared ARI monotherapy with tiapride (TIA). Tic symptoms control
      assessed by Yale Global Tic Severity Scale (Standard Mean Difference (SMD) = 
      0.38 (Confidence Interval (CI) = -1.32 to 0.56); I(2) = 90%, P = 0.42) revealed
      no significant differences between the two groups. Extrapyramidal symptoms were
      significantly different when ARI (1.5%) was compared with haloperidol (HAL)
      (43.5%). No significant group differences were found in the rates of
      nausea/vomiting, dizziness, and dry mouth between ARI and TIA (RR = 0.57 to 1.00
      (95%CI = 0.14-4.20); I(2) = 0% to 69%, P = 0.35 to 1.00). CONCLUSION: This review
      found that ARI has similar efficacy to TIA and HAL for TS, while extrapyramidal
      symptoms were significantly less with ARI than with HAL. ARI can be considered as
      an alternative treatment option for TS.

PMID- 26310196
TI  - Metal-Organic Frameworks as a Versatile Tool To Study and Model Energy Transfer
      Processes.
AB  - Development of materials with efficient and directional energy transfer (ET)
      could significantly modify the existing energy and material landscape. Metal
      organic frameworks (MOFs) are a unique tool to address the upcoming challenges
      related to the enhancement of ET efficiency and directional energy transport. To
      harness MOFs as a versatile platform, mechanistic and structural aspects
      governing ET efficiency should be elucidated. In this context, we review ET
      mechanisms and structural motifs based on the recent advances achieved in MOF
      chemistry and also highlight the possible practical applications that are enabled
      by these studies. 

PMID- 26310195
TI  - Primary proximal tubule injury leads to epithelial cell cycle arrest, fibrosis,
      vascular rarefaction, and glomerulosclerosis.
AB  - Tubular injury has a major etiological role in fibrosis. For many years, this
      relationship has been dominated by the perception that epithelial cells are
      transformed into myofibroblasts that proliferate and generate fibrotic matrix-the
      so-called epithelial-to-mesenchymal transition. Here we focus on mechanisms by
      which injury to the tubule results in fibrosis because of paracrine mechanisms.
      Specific injury to the proximal tubule results in inflammation, reversible
      injury, and adaptive repair if the insult is mild, self-limited in time, and
      occurs in a background of a normal kidney. Repeated injury, in contrast, leads to
      maladaptive repair with sustained tubule injury, chronic inflammation,
      proliferation of interstitial myofibroblasts, vascular rarefaction, interstitial
      fibrosis, and glomerular sclerosis. During the maladaptive repair process after
      the renal insult, many tubular cells become arrested in the G2/M phase of the
      cell cycle. This results in activation of the DNA repair response with the
      resultant synthesis and secretion of pro-fibrotic factors. Pharmacologic
      interventions that enhance the movement through G2/M or facilitate apoptosis of
      cells that otherwise would be blocked in G2/M may reduce the development of
      fibrosis after kidney injury and reduce the progression of chronic kidney
      disease.

PMID- 26310197
TI  - Arabidopsis SMALL ORGAN 4, a homolog of yeast NOP53, regulates cell proliferation
      rate during organ growth.
AB  - Cell proliferation is a fundamental event essential for plant organogenesis and
      contributes greatly to the final organ size. Although the control of cell
      proliferation in plants has been extensively studied, how the plant sets the cell
      number required for a single organ is largely elusive. Here, we describe the
      Arabidopsis SMALL ORGAN 4 (SMO4) that functions in the regulation of cell
      proliferation rate and thus final organ size. The smo4 mutant exhibits a reduced
      size of organs due to the decreased cell number, and further analysis reveals
      that such phenotype results from a retardation of the cell cycle progression
      during organ development. SMO4 encodes a homolog of NUCLEOLAR PROTEIN 53 (NOP53)
      in Saccharomyces cerevisiae and is expressed primarily in tissues undergoing cell
      proliferation. Nevertheless, further complementation tests show that SMO4 could
      not rescue the lethal defect of NOP53 mutant of S. cerevisiae. These results
      define SMO4 as an important regulator of cell proliferation during organ growth
      and suggest that SMO4 might have been evolutionarily divergent from NOP53. 

PMID- 26310198
TI  - Pharmacological Studies of Artichoke Leaf Extract and Their Health Benefits.
AB  - Artichoke (Cynara scolymus) leaf extract was one of the few herbal remedies which
      the clinical and experimental trials have complemented each other. Both
      experimental and clinical effects have been verified through extensive biomedical
      herbal remedy research. Specifically, antioxidant, choleretic, hepatoprotective,
      bile-enhancing and lipid-lowering effects have been demonstrated, which
      corresponded with its historical use. Ongoing research seems to indicate that
      artichoke indeed have medicinal qualities. Most significant appears to be its
      beneficial effect on the liver. In animal studies, liquid extracts of the roots
      and leaves of artichoke have demonstrated an ability to protect the liver, with
      possibly even to help liver cells regenerate. Although research is not yet
      conclusive, scientists were optimistic that its long-standing use in humans for
      digestive and bowel problems was indeed justified. It may also play a role in
      lowering cholesterol and thus help to prevent heart disease. Boiled wild
      artichoke reduced postprandial glycemic and insulinemic responses in normal
      subjects but has no effect on metabolic syndrome patients. This article intended
      to review the wide ranging pharmacological effects of artichoke leaf extract. 

PMID- 26310199
TI  - Custom-Fitted EVA Mouthguards: what is the ideal thickness? a dynamic finite
      element impact study.
AB  - BACKGROUND/AIM: The aim of this study was to evaluate the tooth stresses and
      strains, shock absorption, and displacement during impact of custom-fitted
      mouthguards with different thicknesses. METHODS: Six bar-shaped specimens of the
      EVA were made and subjected to tensile test for elastic modulus assessment. Two
      dimensional plane-strain models of a human maxillary central incisor, periodontal
      ligament, bone support, soft tissue, and mouthguard (MTG) were created. The
      mouthguards were modeled in five different thicknesses (2, 3, 4, 5, and 6 mm).
      One model was created without mouthguard. A nonlinear dynamic impact analysis was
      performed in which a rigid object hit the model at 1 m s(-1). Strain and stress
      (von Mises and Critical modified von Mises) distributions were evaluated, and the
      displacement of the mouthguard with respect to the tooth was calculated. RESULTS:
      The mean [SD] for the EVA elastic modulus was 18.075 [0.457] MPa. The model
      without mouthguard showed the highest stress values at the enamel and dentin
      structures in the tooth crown during the impact. For the MTG models, the location
      of the stress concentrations changed to the root, regardless of the MTG
      thickness, but maximum stresses in the enamel and dentin were lower compared with
      the model without MTG. Increasing the mouthguard thickness did not notably
      decrease the stress-strain values. CONCLUSION: It was concluded that the use of a
      mouthguard promoted lower stresses and strains in teeth during an impact with a
      rigid object. There was no substantial difference in peak stresses and strains
      and in shock absorption among the different mouthguard thicknesses.

PMID- 26310200
TI  - A candidate gastric stem/progenitor cell marker revealed by genome-wide analysis.
AB  - Despite the important role of the gastric stem cell in tissue homeostasis and
      gastric carcinogenesis, its residence and identity remain poorly understood. In a
      recent paper in The Journal of Pathology, Vange et al suggest ASPM as a candidate
      stem/progenitor cell marker for oxyntic glands. Identification of ASPM was
      achieved by genome-wide gene expression analysis of the micro-dissected isthmus
      zone, where the majority of stem/progenitor cells are believed to reside. ASPM
      positive cells, scattered in the proliferative isthmus region, do not express
      most differentiated cell markers and are largely quiescent. Together with ASPM,
      11 other genes that are uniquely expressed in the isthmus zone constitute a
      regulatory network downstream of the core transcription factor E2F1. The authors
      further demonstrated that up-regulation of E2F1 and ASPM is associated with
      gastric cancers. This study provides novel candidates for future lineage-tracing
      experiments that will lead to the ultimate discovery of bona fide gastric stem
      cell markers. Additionally, the E2F1-ASPM axis may represent a new mechanism for
      gastric carcinogenesis.

PMID- 26310201
TI  - Periodic mesoporous organosilica with molecular-scale ordering self-assembled by
      hydrogen bonds.
AB  - Nanoporous materials with functional frameworks have attracted attention because
      of their potential for various applications. Silica-based mesoporous materials
      generally consist of amorphous frameworks, whereas a molecular-scale lamellar
      ordering within the pore wall has been found for periodic mesoporous
      organosilicas (PMOs) prepared from bridged organosilane precursors. Formation of
      a "crystal-like" framework has been expected to significantly change the physical
      and chemical properties of PMOs. However, until now, there has been no report on
      other crystal-like arrangements. Here, we report a new molecular-scale ordering
      induced for a PMO. Our strategy is to form pore walls from precursors exhibiting
      directional H-bonding interaction. We demonstrate that the H-bonded organosilica
      columns are hexagonally packed within the pore walls. We also show that the H
      bonded pore walls can stably accommodate H-bonding guest molecules, which
      represents a new method of modifying the PMO framework. 

PMID- 26310202
TI  - Ex Vivo Intra-arterial Methylene Blue Injection in Rectal Cancer Specimens
      Increases the Lymph-Node Harvest, Especially After Preoperative Radiation.
AB  - BACKGROUND: The examination of as large a number of lymph nodes as possible in
      rectal carcinoma resectates is important for exact staging. However, after
      neoadjuvant radiochemotherapy (RCT), it can be difficult to obtain a sufficient
      number of lymph nodes. We therefore investigated whether staining with methylene
      blue via the inferior mesenteric artery can lead to an increase in the yield of
      lymph nodes in rectal carcinoma tissue after neoadjuvant RCT. METHODS: In a
      prospective, unicentric study rectal carcinoma resectates from three consecutive
      groups of patients were examined (Group I, no staining; Group II, staining with
      methylene blue; Group III, again no staining). The numbers of lymph nodes
      examined were compared (a) between the groups and (b) between patients who had
      not, or who had, received neoadjuvant RCT. RESULTS: In all, 75 rectal carcinoma
      preparations were assessed. The yield of lymph nodes investigated before the use
      of staining (Group I) increased when staining was introduced (Group II), both for
      the patients without neoadjuvant RCT (20.9 vs. 31.3, p = 0.018) and for those who
      did receive this (15.0 vs. 35.1; p = 0.003). After withdrawal of the staining
      procedure (Group III), the lymph-node yield remained high for the patients
      without neoadjuvant RCT (31.3 vs. 30.4; p = 0.882), but it reverted to a lower
      value for those who did receive neoadjuvant RCT (35.1 vs. 24.2; p = 0.029).
      Before the introduction of staining (Group I), significantly fewer lymph nodes
      were examined for patients who received neoadjuvant RCT (15.0 vs. 20.9; p =
      0.039). However, with staining (Group II), no difference was found associated
      with the use or non-use of neoadjuvant RCT (31.3 vs. 35.1; p = 0.520).
      CONCLUSION: The use of methylene blue staining of rectal carcinoma preparations
      leads to a significant increase in the number of lymph nodes examined after
      neoadjuvant RCT. This can be expected to improve the accuracy of lymph-node
      staging of neoadjuvant-treated rectal carcinoma.

PMID- 26310203
TI  - Sr2ZnWO6:Eu3+, Bi3+, Li+: a potential white-emitting phosphor for near
      ultraviolet white light-emitting diodes.
AB  - A series of Sr2ZnWO6 phosphors co-doped with Eu(3+), Bi(3+) and Li(+) were
      prepared using the Pechini method. The samples were tested using X-ray
      diffraction and luminescence spectroscopy. The results show that the samples can
      be effectively excited by near-ultraviolet (UV) and UV light. The introduction of
      Bi(3+) and Li(+) significantly enhances the fluorescence emission of Sr2ZnWO6
      :Eu(3+) and changes the light emitted by the phosphors from bluish-green to
      white. When excited at 371 nm, Sr(2-x-z)Zn(1-y)WO6:xEu(3+), yBi(3+), zLi(+) (x =
      0.05, y = 0.05, z = 0.05, 0.1 and 0.15) samples emit high-performance white
      light. Intense red-orange emission is also observed when excited by UV light. The
      obtained phosphor is a potential white-emitting phosphor that could meet the
      needs of excitation sources with near-UV chips. In addition, this phosphor might
      have promising application as a red-orange emitting phosphor for white light
      emitting diodes based on UV light-emitting diodes.

PMID- 26310204
TI  - Response to "Congenital microtia in a neonate suspected of isotretinoin exposure
      one month before pregnancy: A case report".

PMID- 26310206
TI  - Assessing the Potential Role of Pigs in the Epidemiology of Ebola Virus in
      Uganda.
AB  - Uganda has experienced 4 Ebola outbreaks since the discovery of the virus. Recent
      epidemiological work has shown pigs are hosts for Ebola viruses. Due to their
      high reproduction rates, rapid weight gain, potential to provide quick financial
      returns and rising demand for pork, pig production in Uganda has undergone
      massive expansion. The combination of pork sector growth supported by development
      programmes and Ebola virus risk prompted a foresight exercise using desk,
      interview and spatial methods. The study found that the lack of serological
      evidence for specific reservoir species, the number of human index cases unable
      to account for their source of infection, domestic pig habitat overlap with
      potential Ebola virus zoonotic host environments, reported interactions at the
      human-pig-wildlife interface that could support transmission, fever in pigs as a
      commonly reported problem by pig farmers and temporal correlation of outbreaks
      with peak pork consumption periods warrants further research into potential
      zoonotic transmission in Uganda from pigs.

PMID- 26310205
TI  - APOE/TOMM40 genetic loci, white matter hyperintensities, and cerebral
      microbleeds.
AB  - BACKGROUND: Two markers of cerebral small vessel disease are white matter
      hyperintensities and cerebral microbleeds, which commonly occur in people with
      Alzheimer's disease. AIM AND/OR HYPOTHESIS: To test for independent associations
      between two Alzheimer's disease-susceptibility gene loci--APOE epsilon and the
      TOMM40 '523' poly-T repeat--and white matter hyperintensities/cerebral microbleed
      burden in community-dwelling older adults. METHODS: Participants in the Lothian
      Birth Cohort 1936 underwent genotyping for APOE epsilon and TOMM40 523, and
      detailed structural brain magnetic resonance imaging at a mean age of 72.70 years
      (standard deviation = 0.7; range = 71-74). RESULTS: No significant effects of
      APOE epsilon or TOMM40 523 genotypes on white matter hyperintensities or cerebral
      microbleed burden were found amongst 624 participants. CONCLUSIONS: Lack of
      association between two Alzheimer's disease susceptibility gene loci and markers
      of cerebral small vessel disease may reflect the relative health of this
      population compared with those in other studies in the literature.

PMID- 26310207
TI  - Chemical biology approach for the development of hypoxia inducible factor (HIF)
      inhibitor LW6 as a potential anticancer agent.
AB  - Intratumoral hypoxia has long been considered to be a driving force in tumor
      progression as well as a negative prognostic factor in human cancers. The
      discovery of hypoxia inducible factors (HIFs), which mediate transcriptional
      responses to changes in oxygen levels, has renewed enthusiasm for drug discovery
      and the development of targeted therapies in this field. LW6 represents an
      important new class of small molecules that inhibit HIF-1; it has been major
      source for diverse lead compounds including HIF-1alpha inhibitors. Through a
      chemical biology approach, LW6-derived chemical probes were successfully utilized
      for the identification of the direct targeting of a protein in cancer. LW6
      provides a valuable platform for the discovery and development of small molecule
      inhibitors of HIF-1alpha-dependent tumor progression, metabolic reprogramming,
      and angiogenesis.

PMID- 26310208
TI  - Misassigned natural products and their revised structures.
AB  - Natural products are a major pipeline for drug development and are responsible
      for more than 50 % of drugs on the market. NMR is a fundamental and powerful tool
      for the structure determination of natural products. It is essential to provide
      unambiguous chemical structure information on natural products in drug
      development research, including the structure-activity relationship,
      derivatization and pharmacokinetic/pharmacodynamic studies. Advancement of NMR
      instruments has made it possible to deal with nanomole-scale natural products for
      structure elucidation, but misinterpretation of NMR spectra still occurs. We
      review 21 natural products with revised chemical structures and the methods used
      for those revisions. 

PMID- 26310210
TI  - Inspiring sustainable change.
AB  - In the last issue, we kicked off our dementia series with an article reporting on
      the independent evaluation of the RCN's development programme to improve dementia
      care in acute hospitals. We are now running a series of articles by participants
      in the programme, which present case studies that illustrate the positive work
      achieved ( page 18 ). 

PMID- 26310209
TI  - Ethnic Clusters in Public Housing and Independent Living of Elderly Immigrants
      from the Former Soviet Union.
AB  - The study examines the effects of ethnic clusters and independent living
      arrangements on adaptation of elderly immigrants from the Former Soviet Union.
      The multigenerational living arrangements were compared with independent living
      in a dispersed ethnic community and in an ethnic cluster of public housing. The
      residents of the ethnic clusters of public housing reported poorer health, were
      more reliant on government resources, and experienced greater acculturative
      hassles. However, public housing residents reported significantly larger Russian
      speaking and American social networks, greater American acculturation, higher
      social support from neighbors, as well as lower cultural alienation. In contrast,
      the multigenerational living arrangements were related to greater social support
      from extended family and higher extended family satisfaction. While, the
      independent living in the dispersed ethnic community was associated with smaller
      American social networks and higher levels of cultural alienation. The results
      highlight how the ecologies of different living arrangements are reflected in the
      nature of acculturative, social, and psychological experiences of elderly
      immigrants. 

PMID- 26310211
TI  - Unsafe discharge from hospital highlighted in watchdog report.
AB  - INEFFECTIVE COMMUNICATION and poor co-ordination between services are resulting
      in unsafe hospital discharges, according to an official healthcare watchdog. 

PMID- 26310212
TI  - Consultation announced on Deprivation of Liberty Safeguards.
AB  - DRAFT PROPOSALS for a new framework to protect people who lack mental capacity
      but need to be deprived of their liberty to receive care have been published for
      consultation. 

PMID- 26310213
TI  - Essential services are crucial to tackling loneliness.
AB  - ONE IN five people aged 60 and over who experience loneliness say they have no
      one to turn to, according to a survey. 

PMID- 26310214
TI  - New end of life guidelines welcomed by care community.
AB  - GUIDELINES PROPOSED for the NHS in England should make end of life care
      'clearer', nurse leaders say. RCN professional lead end of life care Amanda
      Cheesley said the draft advice from the National Institute for Health and Care
      Excellence should help staff after controversy over the Liverpool Care Pathway
      (LCP). 

PMID- 26310217
TI  - How are we going to pay for the care of older people?
AB  - IT WAS, tantalisingly, so close. After years of debate it had been decided that,
      from 2016, the amount of money people would need to pay for long-term care in
      older age would be capped for the first time. 

PMID- 26310218
TI  - Reshaping health and social care.
AB  - THE GOVERNMENT'S radical plans to re-structure the way in which health and social
      care are delivered in England saw the formation of 29 pilot sites earlier this
      year. 

PMID- 26310221
TI  - Patients before professionals!
AB  - As author of Dementia: The One Stop Guide I was pleased to read the positive
      aspects of the review published in Nursing Older People (27, 5, 10). 

PMID- 26310222
TI  - Take some time out to reflect.
AB  - AS A participant in the revalidation pilot at Guy's and St Thomas' NHS Foundation
      Trust, I began the process by registering online at the Nursing and Midwifery
      Council (NMC) website. 

PMID- 26310223
TI  - Try to see the bigger picture.
AB  - MANY OLDER people are healthy and live independently or with some support in
      their own homes. However, an increasing ageing population with a varied profile
      of health, functioning and wellbeing means that in later life more people may
      need some form of health and social care and live in various facilities. 

PMID- 26310229
TI  - Practice question.
AB  - What are twiddlemuffs is a question I have been asked many times in the months
      since we introduced these handmade knitted items in Exeter. 

PMID- 26310230
TI  - Understanding the needs of people with dementia and family carers.
AB  - This is the first in a short series that presents case study examples of the
      positive work achieved by trusts who participated in the Royal College of
      Nursing's development programme to improve dementia care in acute hospitals. When
      a person with dementia is in hospital, poor understanding of individual needs and
      preferences can contribute to a lack of person-centred care. Similarly, the needs
      of family carers can often be overlooked and staff do not always appreciate these
      needs at such a stressful time. This article illustrates how three NHS trusts
      have addressed these issues. To help staff get to know patients with dementia,
      Salford Royal NHS Foundation Trust has implemented a patient passport. Similarly,
      The Shrewsbury and Telford Hospital NHS Trust has implemented a carer passport
      that overcomes the restrictions imposed by hospital visiting hours. Royal Devon
      and Exeter NHS Foundation Trust also focused on carers, holding a workshop to
      elicit feedback on what was important to them. This was a useful means of
      engaging with carers and helped staff to realise that even simple changes can
      have a significant effect. 

PMID- 26310231
TI  - Nursing management of urinary tract infections.
AB  - Urinary tract infections (UTIs) are common in older people and can lead to
      serious complications. Infections can worsen underlying medical conditions,
      adversely affect recovery and be alarming to patients, their families and
      caregivers. UTIs have a complex pathophysiology but the most common cause is the
      ascent of bacteria from the periurethral area, which explains their prevalence in
      older women. As a result of antibiotic resistance, an accurate diagnosis is
      imperative and should be based on clinical history, presence of typical signs and
      symptoms and test results. Nurses can assist patients through the diagnostic
      process, treatment and prevention of UTIs, promoting their wellbeing and
      empowerment. This article explores the pathophysiology of UTIs and diagnosis,
      prevention and nursing management in a variety of care settings. 

PMID- 26310232
TI  - Approaches to counter loneliness and social isolation.
AB  - Social isolation and loneliness are significant threats for older people and may
      be associated with mental and physical health problems. This article revisits
      what is meant by social isolation and loneliness and explores the way in which
      social change can trigger both problems. Social networks are discussed as the
      means by which older people can mediate the stresses of change around them. The
      article summarises some of the health consequences of loneliness, indicates some
      simple measures nurses can use to limit the risk of institutional loneliness and
      then examines how collaborative community ventures, mentoring and befriending
      schemes can help older people to access and rebuild social networks that may
      assist them to sustain wellbeing. Case study material is used to highlight
      contrasting profiles of older people who may be either more or less at risk of
      social isolation. 

PMID- 26310233
TI  - Tackling dementia.
AB  - DISCHARGE PLANNING for patients with dementia can be difficult enough when
      arranging local services, so imagine trying to organise a care package for a
      patient being discharged to the US. This is exactly what leading dementia nurse
      Jeni Bell did when the daughter of a patient came to one of the cafes she runs to
      support the carers of patients with dementia at University Hospital Southampton
      NHS Foundation Trust. 

PMID- 26310234
TI  - Retraction of "Development of Biomimetic Tilapia Collagen Nanofibers for Skin
      Regeneration through Inducing Keratinocytes Differentiation and Collagen
      Synthesis of Dermal Fibroblasts".

PMID- 26310235
TI  - Escherichia coli as a model active colloid: A practical introduction.
AB  - The flagellated bacterium Escherichia coli is increasingly used experimentally as
      a self-propelled swimmer. To obtain meaningful, quantitative results that are
      comparable between different laboratories, reproducible protocols are needed to
      control, 'tune' and monitor the swimming behaviour of these motile cells. We
      critically review the knowledge needed to do so, explain methods for
      characterising the colloidal and motile properties of E. coli cells, and propose
      a protocol for keeping them swimming at constant speed at finite bulk
      concentrations. In the process of establishing this protocol, we use motility as
      a high-throughput probe of aspects of cellular physiology via the coupling
      between swimming speed and the proton motive force. 

PMID- 26310236
TI  - Micro/Nano-pore Network Analysis of Gas Flow in Shale Matrix.
AB  - The gas flow in shale matrix is of great research interests for optimized shale
      gas extraction. The gas flow in the nano-scale pore may fall in flow regimes such
      as viscous flow, slip flow and Knudsen diffusion. A 3-dimensional nano-scale pore
      network model was developed to simulate dynamic gas flow, and to describe the
      transient properties of flow regimes. The proposed pore network model accounts
      for the various size distributions and low connectivity of shale pores. The pore
      size, pore throat size and coordination number obey normal distribution, and the
      average values can be obtained from shale reservoir data. The gas flow regimes
      were simulated using an extracted pore network backbone. The numerical results
      show that apparent permeability is strongly dependent on pore pressure in the
      reservoir and pore throat size, which is overestimated by low-pressure laboratory
      tests. With the decrease of reservoir pressure, viscous flow is weakening, then
      slip flow and Knudsen diffusion are gradually becoming dominant flow regimes. The
      fingering phenomenon can be predicted by micro/nano-pore network for gas flow,
      which provides an effective way to capture heterogeneity of shale gas reservoir. 

PMID- 26310237
TI  - A different entity: a population based study of characteristics and recurrence
      patterns in oropharyngeal squamous cell carcinomas.
AB  - BACKGROUND: Cases of squamous cell carcinoma (SCC) of the oropharynx were
      compared with other head and neck cancer (HNC) anatomic subsites in patients
      treated at the provincial referral centre for HNC, the Nova Scotia Cancer Centre
      (NSCC). METHODS: A retrospective chart review was performed on HNC patients
      assessed at the NSCC between 2010 and 2011. Patient demographics, disease
      characteristics, treatment details and outcomes, including recurrence rates and
      survival were collected. Data was collected on new and recurrent cases of HNC.
      This data was compared between the two types of HNC using chi-square tests for
      dichotomous categorical variables or Fishers exact test where appropriate. Wald
      test was used to compare categorical variables with 3 categories. Continuous
      variables were compared using the non-parametric Wilcoxon test. RESULTS: 318
      charts were included in the analysis. 122 (38%) were oropharyngeal squamous cell
      carcinomas (OPSCCs). In terms of disease characteristics, OPSCCs were more likely
      to be poorly differentiated/undifferentiated (n = 267, 49(40%) vs 42(21%), p <
      0.001), non-keratinizing (n = 169, 25(20%) vs 17(9%), p < 0.001), greater than 2
      cm (n = 253, 72(59%) vs 78(40%), p = 0.0061), stage 4 (n = 313, 55(45%) vs
      64(33%), p = 0.0315) and have had locoregional nodal spread (n = 315, 103(84%) vs
      55(28%), p < 0.001). In the subset of 57 patients that had p16 testing, OPSCCs
      were more likely to be p16(+) (37(30%) vs 1(1%), p < .001). There were no
      significant differences in terms of Charlson probability of 10 year survival,
      smoking or alcohol consumption although OPSCC patients were significantly less
      likely to have COPD as a co-morbidity (n = 318, 19(16%) vs 53(27%), p = 0.0175).
      Finally, OPSCCs had less chance for relapse than non-OPSCCs in both univariate
      (2.119 times less, p=0.0034) and multivariate (1.899 times less, p=0.0505)
      analyses along with a 1.822 times less overall mortality in a multivariae
      analysis (p=0.0408). CONCLUSIONS: This analysis suggests that Nova Scotian OPSCCs
      should be considered distinct from other HNC lesions, most notably in terms of
      disease characteristics and prognosis. Specifically, despite a higher association
      with disease factors traditionally considered to be linked to poor prognosis,
      outcomes were actually superior in terms of relapse and overall mortality.

PMID- 26310238
TI  - Synchronous quadruple multiple primary cancers of the tongue, bilateral breasts,
      and kidney in a female patient with a disease-free survival time of more than 5
      years: a case report.
AB  - BACKGROUND: Reports of synchronous multiple primary cancers in patients with oral
      cancer have recently been increasing because of progress in radiographic
      diagnostic techniques. Multiple primary cancers in patients with oral cavity
      cancer mainly occur in the head and neck region, lung, and esophagus. 2-[18F]
      fluoro-2-deoxy-D-glucose positron emission tomography is usually used to identify
      synchronous multiple primary cancers. CASE PRESENTATION: We herein describe a 69
      year-old woman diagnosed with synchronous quadruple multiple primary cancers,
      namely a squamous cell carcinoma of the mobile tongue, invasive ductal carcinoma
      of the right breast, intraductal carcinoma of the left breast, and chromophobe
      renal cell carcinoma of the right kidney. We removed the four tumors over three
      surgical procedures to reduce the surgical risk because the patient had diabetes
      mellitus. To the best of our knowledge, this combination of multiple primary
      cancers has not been reported to date. Importantly, we followed this case for 5
      years after surgery. The patient was alive and well with no clinical or
      radiologic signs of recurrent or metastatic disease at the time of this writing.
      CONCLUSIONS: In the present case, the kidney cancer could not be detected by 2
      [18F]-fluoro-2-deoxy-D-glucose positron emission tomography but could be detected
      by contrast-enhanced computed tomography. To avoid overlooking multiple primary
      cancers of the kidney, we suggest that contrast-enhanced computed tomography
      should cover a region extending to the inferior margin of the kidney, rather than
      only to the liver, in patients with oral cavity cancer.

PMID- 26310239
TI  - A 3-dimensional fibre scaffold as an investigative tool for studying the
      morphogenesis of isolated plant pells.
AB  - BACKGROUND: Cell culture methods allow the detailed observations of individual
      plant cells and their internal processes. Whereas cultured cells are more
      amenable to microscopy, they have had limited use when studying the complex
      interactions between cell populations and responses to external signals
      associated with tissue and whole plant development. Such interactions result in
      the diverse range of cell shapes observed in planta compared to the simple
      polygonal or ovoid shapes in vitro. Microfluidic devices can isolate the dynamics
      of single plant cells but have restricted use for providing a tissue-like and
      fibrous extracellular environment for cells to interact. A gap exists, therefore,
      in the understanding of spatiotemporal interactions of single plant cells
      interacting with their three-dimensional (3D) environment. A model system is
      needed to bridge this gap. For this purpose we have borrowed a tool, a 3D nano-
      and microfibre tissue scaffold, recently used in biomedical engineering of animal
      and human tissue physiology and pathophysiology in vitro. RESULTS: We have
      developed a method of 3D cell culture for plants, which mimics the plant tissue
      environment, using biocompatible scaffolds similar to those used in mammalian
      tissue engineering. The scaffolds provide both developmental cues and structural
      stability to isolated callus-derived cells grown in liquid culture. The protocol
      is rapid, compared to the growth and preparation of whole plants for microscopy,
      and provides detailed subcellular information on cells interacting with their
      local environment. We observe cell shapes never observed for individual cultured
      cells. Rather than exhibiting only spheroid or ellipsoidal shapes, the cells
      adapt their shape to fit the local space and are capable of growing past each
      other, taking on growth and morphological characteristics with greater complexity
      than observed even in whole plants. Confocal imaging of transgenic Arabidopsis
      thaliana lines containing fluorescent microtubule and actin reporters enables
      further study of the effects of interactions and complex morphologies upon
      cytoskeletal organisation both in 3D and in time (4D). CONCLUSIONS: The 3D
      culture within the fibre scaffolds permits cells to grow freely within a matrix
      containing both large and small spaces, a technique that is expected to add to
      current lithographic technologies, where growth is carefully controlled and
      constricted. The cells, once seeded in the scaffolds, can adopt a variety of
      morphologies, demonstrating that they do not need to be part of a tightly packed
      tissue to form complex shapes. This points to a role of the immediate nano- and
      micro-topography in plant cell morphogenesis. This work defines a new suite of
      techniques for exploring cell-environment interactions.

PMID- 26310240
TI  - Daytime Sleepiness in Men During Early Fatherhood: Implications for Work Safety.
AB  - This study measured the daytime sleepiness (DS) and work safety of fathers during
      the first 12 weeks of their babies' lives (i.e., early fatherhood). A
      questionnaire was developed using the Epworth Sleepiness Scale (ESS), the Safety
      Behaviour at Work Scale, a self-reported sleep history, and a work-related
      incident history. Of the 221 participants, the vast majority reported they
      experienced less than 6 hours of interrupted sleep per night during the 12 weeks
      of the study, and an increasing frequency and severity of DS. The study also
      revealed an inverse correlation between ESS and Safety Behaviour at Work scores;
      fathers were 14% more likely to report a near-miss accident at work at 12 weeks.
      This study posits that antenatal classes and assessment of fathers' sleepiness at
      work by occupational health practitioners could assist fathers in reducing
      daytime sleepiness and mitigating the risk of workplace incidents. 

PMID- 26310242
TI  - Corrigendum.

PMID- 26310241
TI  - Rhodococcus lactis sp. nov., an actinobacterium isolated from sludge of a dairy
      waste treatment plant.
AB  - A Gram-stain-positive, non-motile and aerobic bacterium, designated strain
      DW151BT, was isolated from a sludge sample of a dairy industry effluent treatment
      plant. 16S rRNA gene sequence analysis of strain DW151BT placed it within the
      genus Rhodococcus. It displayed significant similarity with recognized species of
      the genus: Rhodococcus pyridinivorans PDB9T (98.8 %), Rhodococcus gordoniae W
      4937T (98.6 %), Rhodococcus rhodochrous DSM 43241T (98.5 %) and Rhodococcus
      artemisiae YIM 65754T (97.5 %). However, strain DW151BT differed from
      phylogenetically closely related species in various phenotypic properties. The
      cellular polar lipid profile consisted of diphosphatidylglycerol (DPG),
      phosphatidylethanolamine (PE) and phosphatidylinositol (PI) as major lipids, MK
      8(H2) was the major menaquinone and meso-diaminopimelic acid was the cell-wall
      peptidoglycan. The fatty acid profile consisted of C16 : 0, C18 : 1cis9 and C16 :
      1cis9 as main components. The presence of C16 : 0 and diphosphatidylglycerol as
      major fatty acid and polar lipid, respectively, was in accordance with
      chemotaxonomic markers of the genus Rhodococcus. The DNA G+C content of strain
      DW151BT was 69.9 mol%, a value within the limits reported for the members of this
      genus. Furthermore, strain DW151BT showed low similarity at the whole genome
      level in DNA-DNA hybridization experiments with phylogenetically closely related
      strains. Considering the low similarity at the genome level and differences in
      phenotypic properties, strain DW151BT is considered to represent a novel species
      of the genus Rhodococcus, for which the name Rhodococcus lactis sp. nov. is
      proposed. The type strain is DW151BT ( = MTCC 12279T = DSM 45625T).

PMID- 26310243
TI  - A survey of the availability, prices and affordability of essential medicines in
      Jiangsu Province, China.
AB  - BACKGROUND: Field surveys conducted in China before the implementation of the
      essential medicine policy showed that Chinese individuals faced less access to
      essential medicines. This paper aims to evaluate the availability, prices and
      affordability of essential medicines in Jiangsu Province, China after the
      implementation of the policy in 2009. METHODS: A cross-sectional survey was
      conducted in Jiangsu in 2013 using the World Health Organization/Health Action
      International (WHO/HAI) methodology. Data on the availability and prices of 50
      essential medicines were collected from the public and private healthcare
      sectors. RESULTS: The mean availabilities of innovator brands and lowest priced
      generics (LPGs) were 11.5% and 100% in primary healthcare facilities, 36.8% and
      32.6% in the secondary and tertiary sectors, and 18.7% and 42.9% in the private
      sector, respectively. The median price ratios (MPRs) were 1.26 to 2.05 for
      generics and 3.76 to 27.22 for innovator brands. Treating ten common diseases
      with LPGs was generally affordable, whereas treatment with IBs was less
      affordable. CONCLUSIONS: The high availability of LPGs at primary healthcare
      facilities reflects the success of the essential medicine policy, while the low
      availability in secondary and tertiary levels and in private pharmacies reflects
      a failure to implement the policy in these levels. The health policy should be
      fully developed and enforced at the secondary and tertiary levels and in the
      private sector to ensure equitable access to health services.

PMID- 26310244
TI  - Sexual, irritative, and voiding outcomes, following stereotactic body radiation
      therapy for prostate cancer.
AB  - BACKGROUND: Urinary symptoms and sexual dysfunction are the two most common
      complaints following prostate radiotherapy. The impact of hypofractionated
      treatment on sexual function, irritative symptoms, and voiding symptoms has not
      been determined within the same patient population. Here we present our
      institutional data on sexual function, voiding function, irritative symptoms, and
      treatment response following SBRT. METHODS: This retrospective analysis includes
      102 non-metastatic patients treated with SBRT at a single institution between May
      2008 and September 2014. The course of radiotherapy consisted of 36.25 Gy (range
      35-40) over five daily fractions. International Prostate Symptom Score (IPSS),
      Sexual Health Inventory for Men (SHIM), and PSA were recorded at baseline, 1, 3,
      6, 9, 12, 18, 24, and 36 months after treatment. RESULTS: Median patient age was
      72 years old with a median follow-up of 4.3 years. Pretreatment IPSS-I score was
      5.21, increasing to 6.97 (p < .001) after 1 month. The mean IPSS-I score returned
      close to baseline after 3 months to 5.86 and decreased to below baseline after 2
      years to 5.09. At 3 months, 9 months, and 2 years, 47.5, 76.2, and 91.1% of
      patients had reached IPSS-I resolution. The mean IPSS-O score prior to treatment
      was 5.31 and there was an increase in the score to 6.45 (p = 0.344) at 1 month.
      The score remained close to baseline and decreased to 4.00 at 2 years and
      significantly decreased to 3.74 (p = 0.035) at 3 years. 64.4, 82.1, and 96.0% of
      patients had IPSS-O resolution by 3 months, 9 months, and 2 years. The mean SHIM
      score prior to treatment was 13.52 and continually decreased to below baseline a
      year after treatment to 10.56 (p < .001). SHIM score began to improve at 18
      months, but was still significantly less than baseline at 12.12 (p = .01).
      CONCLUSIONS: While an increase in AUA/IPSS score initially occurred, all patients
      resume normal activities immediately following treatment and the AUA/IPSS
      symptoms improved from baseline. Irittative symptoms take longer to resolve when
      compared to obstructive voiding symptoms in patients treated with SBRT. Three
      year PSA response, reported toxicity, erectile function preservation, and urinary
      function improvement, shows favorable results.

PMID- 26310247
TI  - Investigative Approaches for Oral Delivery of Anticancer Drugs: A Patent Review.
AB  - Typically, chemotherapy has been dominated by intravenous administration. Though,
      inclination towards oral ingestion of chemotherapeutics is increasing since it
      offers ample of fascinating opportunities including better quality of life,
      treatment advantages and low healthcare cost. However, low or moderate
      bioavailability along with significant inter-patient variability and narrow
      therapeutic window challenges their oral administration. Thus, optimization of
      oral route with maximized efficacy and miniminal adverse events is a challenging
      area. To surmount the challenges, a number of strategies like P-glycoprotein (P
      gp) modulation, colloidal carrier etc. have been under investigation and
      scientists are exploring the utility of solid dispersions, prodrugs,
      biconjugates, complexes, microparticulate, and nanoparticulate systems (liposome,
      SLN, dendrimers, SEDDS, nanoparticles). Among these, nanoparticulate systems have
      shown promising results due to their targeting potential and ability to alter
      absorption pathways. Functional excipients with P-gp modulating activity are also
      being explored for more effective oral delivery of chemotherapeutics. This
      article explores the encouraging reports, recent patents and inventions on the
      feasibility and applicability of oral administration of chemotherapeutics. 

PMID- 26310248
TI  - [Change to "prevention of the avoidable blindness and visual impairment" from
      "prevention of blindness"].
AB  - The formulation on the eye health by WHO had an obvious change in recent years.
      Before 2006, WHO and WHA solutions clearly put forward the prevention of
      blindness. After 2006, WHO and WHA solutions on the eye health emphasized the
      elimination of the avoidable blindness and visual impairment. This change extends
      the scope of eye health, reflects the important progress on the global eye
      health, and also reflects the social progress and the increase to the need on eye
      health by the public. This change conforms to the actual situation in China. It
      is necessary to adopt elimination of the avoidable blindness and visual
      impairment as the priorities in eye health in making the 13th national plan of
      blindness prevention. This change is not merely a matter of wording, but also a
      great change in the working content in eye health. The change demonstrates the
      deep development on the eye health, and may benefit more people and promote the
      further development of eye health and ophthalmology in China. 

PMID- 26310245
TI  - Human and Pathogen Factors Associated with Chlamydia trachomatis-Related
      Infertility in Women.
AB  - Chlamydia trachomatis is the most common bacterial sexually transmitted pathogen
      worldwide. Infection can result in serious reproductive pathologies, including
      pelvic inflammatory disease, ectopic pregnancy, and infertility, in women.
      However, the processes that result in these reproductive pathologies have not
      been well defined. Here we review the evidence for the human disease burden of
      these chlamydial reproductive pathologies. We then review human-based evidence
      that links Chlamydia with reproductive pathologies in women. We present data
      supporting the idea that host, immunological, epidemiological, and pathogen
      factors may all contribute to the development of infertility. Specifically, we
      review the existing evidence that host and pathogen genotypes, host hormone
      status, age of sexual debut, sexual behavior, coinfections, and repeat infections
      are all likely to be contributory factors in development of infertility. Pathogen
      factors such as infectious burden, treatment failure, and tissue tropisms or
      ascension capacity are also potential contributory factors. We present four
      possible processes of pathology development and how these processes are supported
      by the published data. We highlight the limitations of the evidence and propose
      future studies that could improve our understanding of how chlamydial infertility
      in women occurs and possible future interventions to reduce this disease burden. 

PMID- 26310246
TI  - Over-expressing Akt in T cells to resist tumor immunosuppression and increase
      anti-tumor activity.
AB  - BACKGROUND: Tumor employs various means to escape immunosurveillance and inhibit
      immune attack, and strategies have been developed to counteract the inhibitory
      signals. However, due to the complex suppressive mechanisms in the tumor
      microenvironment, blocking one or a few inhibitory signals has only limited
      effects on therapeutic efficacy. Instead of targeting tumor immunosuppression, we
      considered from another point of view, and hypothesized that manipulating T cells
      to make them resist any known or unknown suppressive mechanism may be more
      effective for cancer treatment. METHODS: We used OT-1 cells transduced with
      retroviruses encoding Akt and human peripheral blood lymphocytes (PBLs)
      transduced with retroviruses encoding both Akt and a chimeric antigen receptor
      (CAR) specific for tumor antigen EpCAM to examine the effect of over-expressing
      Akt on tumor specific T cells in tumor environment. RESULTS: We show that Akt
      activity of T cells in the tumor environment was inhibited, and over-expressing
      Akt in OT-1 cells increased the cytokine production and cell proliferation in the
      presence of B16-OVA tumor cells. What's more, adoptive transfer of OT-1 cells
      over-expressing Akt inhibited B16-OVA tumor growth and prolonged mouse survival.
      To examine if over-expressing Akt could increase the anti-tumor activity of T
      cells in human cancer, PBLs co-expressing EpCAM specific CAR and Akt were
      cultured with EpCAM-expressing human prostate cancer cells PC3M, and less
      inhibition on cell proliferation and less apoptosis were observed. In addition,
      adoptive transfer of PC3M specific T cells over-expressing Akt resulted in more
      dramatic tumor inhibitory effects in PC3M bearing NOD/SCID mice. CONCLUSIONS:
      These data indicates that over-expressing Akt in tumor specific T cells increases
      T cell proliferation and activity in the tumor environment, and enhances anti
      tumor effects of adoptively transferred T cells. Our study provides a new
      strategy to improve the efficacy of adoptive T cell therapy, and serves as an
      important foundation for clinical translation.

PMID- 26310249
TI  - [Enlightenment and thinking of blinding trachoma elimination in China].
AB  - Trachoma had been the leading infectious cause of blindness. After years of hard
      work and unremitting efforts, blinding trachoma would never been a public health
      problem in China by 2015. Discovery and research of Chlamydia trachoma provide a
      scientific way for the prevention and control of trachoma. The achievement of
      eliminating blinding trachoma in China pertained to the highly concerned about
      government and succeed spreading of SAFE strategies. It is still required to
      strengthen the diagnostic criteria and knowledge training of public health
      disease. Epidemiological investigation should follow the international criteria.
      Though blinding trachoma would never been a public health problem in China,
      comprehensive prevention and control of trachoma should be emphasized in case of
      being epidemic again. 

PMID- 26310250
TI  - [The prevalence of appositional angle closure among adults aged 50 years or above
      in Funing county Jiangsu Province].
AB  - OBJECTIVE: The purpose of the study is to determine the prevalence of
      appositional angle closure in persons aged 50 or above in Funing County. METHODS:
      Cluster sampling randomly selected residents in Funing County aged 50 years or
      above. From March to May 2010, 484 eyes of 243 patients with the shallow
      peripheral anterior chamber and the anatomic narrow chamber angle, which was
      determined by Van Herick technique and gonioscopy, were collected from 5202
      individuals. The presence of appositional angle closure and the angle-opening
      distance (AOD) was determined with photopic and scotopic ultrasound biomicroscopy
      (UBM) in eight positions. Paired chi2 test and paired t test (SPSS 17.0) were
      used to determine any significant differences at P < 0.05. RESULTS: The
      prevalence of appositional angle closure was found at least one position in 337
      eyes (69.6%) by scotopic UBM and in 116 eyes (24.0%) by photopic UBM. The
      prevalence of appositional angle closure was significantly higher by scotopic UBM
      than by photopic UBM (chi2 = 204.36, P < 0.001 respectively), and was the highest
      in superior quadrant. The AOD varied significantly among the eight positions and
      was significantly narrower by scotopic UBM than by photopic UBM (t = 6.039,
      6.883, 11.612, 11.157, 4.732, 6.798, 5.156, 4.071; P < 0.001). Since 197 persons
      (81.07%) were found anterior angle closure by scotopic UBM, we estimated the
      prevalence of appositional angle closure was 5.40% (95% CI: 4.80%-6.05%) among
      adults aged 50 or above in Funing County. CONCLUSIONS: The prevalence of
      appositional angle closure was higher than previous surveys, the possible reason
      is that scotopic UBM could find early appositional angle closure more preferably.

PMID- 26310251
TI  - [Investigation and strategy research of eye disease prevention resources in
      community health service centers in Shanghai].
AB  - OBJECTIVE: To investigate the status of eye disease prevention resources in
      community health service centers, to understand the distribution of ophthalmology
      service resources in each community, and to understand the main problems existing
      in the work of blindness prevention and treatment in Shanghai, so as to
      strengthen the prevention of blindness and improve the primary eye care level.
      METHODS: Using the survey method, we carried out the investigation of disease
      control and prevention resources in all community health service centers to
      obtain the data of eye disease prevention and treatment resources. Using the
      descriptive statistics, we described the distribution of resources of eye disease
      prevention and treatment in different districts. RESULTS: There were 244
      communities in 17 districts and counties in Shanghai, of which 236 (96.72%)
      communities participated in the survey and completed the questionnaires. Forty
      nine (20.8%) communities had independent outpatient departments of ophthalmology,
      96 (40.7%) had departments of ophthalmology and otorhinolaryngology, 33 (14%) had
      ophthalmology doctor visits from secondary or tertiary medical institutions, and
      87 (36.9%) had no outpatient department of ophthalmology. There were 82 oculists,
      129 general or otorhinolaryngology doctors treating eye disease, 9 ophthalmic
      nurses, and 1 optometrist. There were 36 specialized personnel for public health
      of eye protection and 217 part-time personnel. Moreover, there were a total of 1
      103 pieces of ophthalmic equipment in all communities with the use rate of 91%.
      CONCLUSIONS: Uneven ophthalmology resources and eye care professional ability in
      community health service centers, lack of technical and public health personnel
      for prevention of eye disease, backward eye disease screening equipment, and
      inadequate investment in prevention and treatment of eye disease are major
      problems. More government supports for prevention and treatment of eye disease in
      communities and continuous improvement in three-level blindness prevention
      network systems and information construction are needed.

PMID- 26310252
TI  - [Hebei Province Ophthalmologists current situation survey 2013].
AB  - OBJECTIVE: This survey is conducted by Hebei Society of Ophthalmology to
      understand the current situation of the department of ophthalmology in Hebei
      province, in order to help the Branch to develop an effective, highly-targeted
      and practical continuing education program. METHODS: A questionnaire is used in
      this survey, which consists of 4 sections and 25 items, covering Basic
      Information, Hospital and Department, Personal Practice and Open-ended Questions.
      The questionnaire is distributed and collected by the Society of Ophthalmology of
      each region in Hebei province to all medical institutions in their area which
      have the ability to carry out ophthalmic clinical work. After the aggregation of
      the questionnaire and according to the omission, Hebei Society of Ophthalmology
      contacts the individuals who missed the survey by direct calls, letter post and
      email, etc. to finish the survey. RESULTS: This survey covers 121 counties and
      cities (coverage 85.8%), 305 medical institutions and 1 485 ophthalmologists.
      Results shows that trained ophthalmologists take a high proportion (84.3%) in all
      hospitals, the percentage of ophthalmologists who are eager to learn and improve
      is high (94.8%), the percentage of ophthalmologists having a Bachelor degree or
      above is high (68.9%). However, the percentage of ophthalmologists having a
      Master or Doctor degree is relatively low (19.6%), the talents who can
      independently carry out vitrectomy are insufficient (4.1%), the percentage of the
      medical institutions not having basic ophthalmic equipment is high (37.3%).
      CONCLUSIONS: The reasons restraining the development of Ophthalmology in Hebei
      province include the lack of professional talents and ophthalmic equipment. The
      contradiction between the increasing demand of the public for ophthalmological
      treatment and the limited medical service level we can provide is the primary
      contradiction in the departments of Ophthalmology in Hebei province. After the
      survey and according to the results, Hebei Society of Ophthalmology will organize
      more training to meet the desire and interest of the ophthalmologists in our
      province, to achieve the ultimately goal of improving the Ophthalmic medical
      level throughout the province.

PMID- 26310253
TI  - [A study of refractive state in premature infants without retinopathy of
      prematurity and full-term children at the age of 0 to 6].
AB  - OBJECTIVE: To investigate the development of the refractive status in premature
      infants full-term children aged 0 to 6 years old. METHOD: Case control study. One
      thousand one hundred and sixtyfour premature infants and One thousand one hundred
      and ninety-one full-term children were collected from September 2011 to September
      2012 in Renmin Hospital of Wuhan University, among them, one thousand and eighty
      eight premature infants premature infants (2 176 eyes) without retinopathy of
      prematurity (ROP) and one thousand one hundred and two cases of full-term
      children (2 204 eyes) were included in the study. Refraction with cycloplegic
      retinoscopy was determined. The corneal curvatures and axial lengths of premature
      infants aged 3 to 6 years old were measured by Optical coherence interferometry.
      RESULTS: (1) The incidence of myopia and astigmatism were 9.1% and 35.4% in
      premature infants aged 0 to 6 years old, and 4.4%, 18.9% in full-term children.
      (2) The spherical diopter, cylindrical lens diopter and spherical equivalent
      degree were (1.15 +/- 0.87), (0.84 +/- 0.71) and (1.47 +/- 0.28) D, three types
      of refractive value reduced progressively along with increasing age. (3) Changes
      in spherical equivalent degree in preterm children are associated with axial
      length, corneal curvature, gestational age, birth weight and age (r = -0.232,
      0.112, 0.117, 0.254, -0.215, P = 0.000, 0.009, 0.008, 0.000, 0.001). CONCLUSIONS:
      The incidence of myopia of premature infants without ROP was higher than that of
      full-term children; The emmetropization of premature infants begins earlier than
      full-term children.

PMID- 26310254
TI  - [Early clinical evaluation of contrast visual acuity in patients with age-
      related cataract].
AB  - OBJECTIVE: To evaluate the changes of the contrast visual acuity (CVA) in early
      agerelated cataract patients. METHODS: Case-controlled study. One hundred and
      four eyes of 52 age-related cataract patients, with the best corrected visual
      acuity equal to or more than 0.8, equivalent spherical diopters of -3.00 to 3.00
      DS and astigmatic diopters of -1.50 to 1.50 DC, were selected as the cataract
      group. Another 104 eyes of 52 normal adults, with the best corrected visual
      acuity equal to or more than 0.8, equivalent spherical diopters of -3.00 to 3.00
      DS and astigmatic diopters of -1.50 to 1.50 DC, were selected as the control
      group. They were paired according to sex, the similar age and the best corrected
      visual acuity. After eye and refractive examinations, all examinees received the
      CVA measurements in different contrast levels between the optotypes and
      background (100%, 25%, 10% and 5%) in the dark room by the multifunction visual
      acuity chart. SPSS 18.0 software package was used for paired t test. RESULTS: In
      the cataract group, CVA decreased more significantly than the control group. OD:
      0.99 +/- 0.26, 0.59 +/- 0.23, 0.38 +/- 0.19, 0.23 +/- 0.12. OS: 0.98 +/- 0.28,
      0.59 +/- 0.18, 0.38 +/- 0.14, 0.23 +/- 0.10. OU: 1.15 +/- 0.26, 0.73 +/- 0.20,
      0.49 +/- 0.16, 0.30 +/- 0.10 (OD: t = -6.49, -7.25, -7.57, -5.45. OS: t = -5.78, 
      7.51, -6.41, -7.16. OU: t = -4.33, -7.60, -7.53, -9.75, P < 0.01). There was a
      significant decrease in different degrees of cortical cataract (F100% = 50.18, P
      = 0.000. F25% = 23.08, P = 0.000. F10% = 20.17, P = 0.000. F5% = 13.42, P =
      0.000). There was a significant decrease in different degrees of cortical
      cataract compared with the control group (C1: t = -6.49, -7.25, -7.57, -5.45, P <
      0.05. C2: t = -5.78, -7.51, -6.41, -7.16, P < 0.01. C3: t = -4.33, -7.60, -7.53, 
      9.75, P < 0.01). CONCLUSION: CVA was more reliable than the best corrected visual
      acuity in evaluating vision function in patients with early age-related cataract.

PMID- 26310255
TI  - [The long-term clinical effects of orthokeratology in high myopia children].
AB  - OBJECTIVE: To investigate the long-term clinical effects of orthokeratology
      (ortho-k) in high myopia children with 5 years of follow-ups. METHODS:
      Prospective study. We chose 30 high myopia patients to wear ortho-k contact
      lenses (CLs) for controlling or delaying myopia progression from 2003. Among
      them, there were 10 boys and 20 girls whose average age was (15 +/- 2) years,
      spherical diopters were (-7.34 +/- 0.91) D, corneal astigmatism diopters were (
      1.06 +/- 0.62) D, uncorrected visual acuity was LogMAR 0.89 +/- 0.29, corneal
      flattened curvature was (43.54 +/- 1.16) D, and axial length was (26.38 +/- 0.94)
      mm. All patients, with informed consent before fitting of ortho-k CLs, had
      conventional refraction and ocular tests. We compared the values of spherical
      diopters, visual acuity, corneal flattened curvature and axial length before and
      6 months, 1 year, 2 years, 3 years, 4 years and 5 years after wearing CLs,
      respectively. The results were analyzed by SPSS 16.0 software. RESULTS: During
      the five years of observation periods, all patients' visual acuity and corneal
      flattened curvature were different from the pre-fitting (P < 0.05). Compared to
      the pre-fitting, the naked visual acuity was some degree improved, it was LogMAR
      0.45 +/- 0.31, 0.49 +/- 0.32, 0.43 +/- 0.30, 0.47 +/- 0.31, 0.58 +/- 0.35, 0.53
      +/- 0.27, respectively. F = 10.725, P = 0.000. Corneal flatten curvature was tend
      to be flatter, such was 41.14 +/- 1.54, 41.75 +/- 1.88, 41.54 +/- 2.10, 41.73 +/-
      1.89, 41.94 +/- 1.61, 40.70 +/- 1.67. F = 10.161, P = 0.000 (All P < 0.05). The
      spherical diopters during the first two years after wearing ortho-k CLs were
      significantly reduced, compared with the previous values (it was -5.23 +/- 1.81, 
      5.59 +/- 2.75, -6.29 +/- 2.12, -6.63 +/- 2.31, -6.83 +/- 2.33, -7.01 +/- 1.81,
      respectively, F = 4.929, P = 0.000), and kept stable in the long-term
      observation. The axial length checked at 5 years was slightly elongated (it was
      26.41 +/- 0.90, 26.68 +/- 0.93, 26.69 +/- 1.06, 26.75 +/- 0.94, 26.81 +/- 1.04,
      27.04 +/- 1.01. F = 1.831, P = 0.094). The axial elongation was retarded by using
      ortho-k CLs in high myopia children. All patients were not subjected to severe
      complications which may lead to quitting the enrollments. CONCLUSIONS:
      Orthokeratology used in controlling or delaying high myopia progression is
      definitely outstanding in 5 years observations. Standard lens wearing and regular
      lens check improve safety of lens use in high myopia.

PMID- 26310256
TI  - [The study of the changes of ultra- microstructure after a momentary action of
      femtosecond laser with human corneal tissue in vivo].
AB  - OBJECTIVE: To observe the changes of pathology and ultra- microstructure of
      corneal lenticules extracted by femtosecond laser small incision lenticule
      extraction surgery and to investigate instantaneous damage of photodisruption of
      femtosecond laser to human corneal tissue in vivo. METHODS: The small incision
      lenticule extraction surgeries in 25 myopic eyes were performed with Carl Zeiss
      VisuMax femtosecond laser, and the lenticules were observed by light microscopy,
      scanning electron microscopy and transmission electron microscopy. RESULTS: Light
      microscopy showed slight edema in part of the collagen fibers in the cornea
      lenticule tissue. A thin layer of deep tissue dyeing at the edge of the lenticule
      was observed on a linear array. In the center of superficial lenticule tissue
      existed a few bubbles. Under the scanning electron microscope, the anterior
      surface of the lenticule was found to be relatively smooth, with no obvious
      tissue bridge. The posterior surface of the lenticule was slightly irregular
      compared with the anterior surface. Scattered tissue bridges and residual traces
      of the effect of femtosecond laser photodisruption could be observed. Under the
      transmission electron microscope, adjacent collagen fiber layers in the corneal
      lenticule matrix were detected to cross each other regularly, with no breakage of
      the collagen fibers or separation of the layers. The incision of the collagen
      fibers on one side of the lenticule was on a linear alinement. It can also be
      observed that the central part of the lenticule was mildly damaged. However, the
      stroma cells near the lenticule limbus were severely damaged. Part of the corneal
      stroma cells were solidified with several shivers, which might be due to the
      photodisruption. Some of the damaged corneal stroma cells were observed with
      remnants, while the spaces occupied by part of the corneal cells became
      fractured. CONCLUSIONS: Obvious damage of the femtosecond laser to the corneal
      tissue at early stage was not observed. At the edge of the area where femtosecond
      laser focused, there were mild thermal injury and slight structure change. There
      were not abnormal appearances of the tissue structure at the non-focus area.

PMID- 26310257
TI  - [Characteristics of refractive status of mutant Lumican transgenic mice].
AB  - OBJECTIVE: To investigate the change of refractive status in transgenic mice with
      mutant Lumican (bright proteoglycan) gene at different ages. METHODS:
      Experimental Study. Fifty-four 3-week-old with mutant Lumican gene (cDNA 596T >
      C) mice (27 male and 27 female) were randomly divided into 9 groups (n = 6, half
      male and half female) by random number table. One group (3-week-old) was randomly
      chosen and measured the refractive status by retinoscopy after mydriasis.
      Measurement of other groups were repeated the method above respectively in the
      fourth, fifth, sixth, eighth, tenth, twelfth, sixteenth, and twentieth week.
      Differences of diopter between right and left eye and between male and female
      were compared within each group by paired t test. The differences of mice's
      diopters in different age were compared by Kruskal-Wallis H test. Pairwise
      comparisons were acquired by Mann-Whitney U test. RESULTS: There were no
      statistic difference of diopters between binoculus: The mice's diopters of right
      and left eyes were respective measured in the twentieth week (1.50 +/- 0.45) D
      and (1.25 +/- 0.42) D (t = -0.889, P > 0.05), The mice's diopters of right and
      left eyes were respective measured in the third week (-2.50 +/- 2.59) D and (
      2.50 +/- 4.32) D (t = 0.000, P > 0.05); There were no statistic difference of
      diopters between different genders: The mice's diopters of female and male were
      respective measured in the third week (-0.5 +/- 3.83) D and (-4.17 +/- 1.94) D,
      (t = 2.079, P > 0.05), The mice's diopters of female and male were respective
      measured in the twelfth week (1.50 +/- 0.84) D and (1.50 +/- 1.87) D (t = 0.000,
      P > 0.05); Analysis of binocular diopters revealed significant differences among
      nine groups (H = 20.910, P < 0.05). Diopters measured in the third week (-2.50 +/
      3.40D) and the sixth week (+3.25 +/- 2.67) D had statistical difference (Z = 
      3.259, P < 0.001). There were no statistical significance between other groups (P
      > 0.001). CONCLUSIONS: Characteristics of diopters gathered from mice with
      Lumican gene mutation at different weeks are summarized as follows: Myopia could
      be observed in the third week. And this situation of myopia was gradually
      transformed into hyperopia with aging. The maximum hyperopic diopter was observed
      at 6th-week-old mice. From the eighth to twentieth week, the degree of hyperopic
      diopter gradually decreased and stabilized.

PMID- 26310258
TI  - [Research advances of Descemet's membrane endothelial keratoplasty].
AB  - In the past ten years, corneal endothelial keratoplasty has been widely and
      successfully performed in China. As an ideal surgical treatment for corneal
      endothelial diseases, Descemet's membrane endothelial keratoplastywas only tried
      out in few hospitals. This article summarized the development of Descemet's
      membrane endothelial keratoplasty in surgical indications, operation process and
      postoperative complications in China and abroad for providing references for
      clinical application. 

PMID- 26310259
TI  - [The progress of studies on intraocular lens implantation in cataract with high
      myopia].
AB  - With development of the technology of cataract surgery, combined
      phacoemulsification and intraocular lens implantation in cataract with high
      myopia has been widely carried out in clinical treatment. Due to the
      particularity of high myopia, phacoemulsification in patients with cataract and
      high myopia is difficult and has recently received a lot of attentions. In this
      paper, preoperative examinations, the selection of intraocular lenses, surgery
      methods and surgical complications of cataract surgery in patients with cataract
      and high myopia are briefly reviewed. 

PMID- 26310260
TI  - [New approaches to visual rehabilitation training for patients with visual field
      defects].
AB  - In clinical practice, maculopathy and neurological eye disorders often cause
      visual field defects. Once the defects are formed, treatment and rehabilitation
      are confronted with the bottleneck due to irreversibility. With the
      transformation of medical patterns and people's higher needs for rehabilitation,
      new approaches to visual training for these diseases with visual field defects
      are emerging. Currently, visual rehabilitation training for patients with visual
      field defects focuses on two directions: central visual field defects and
      hemianopia / peripheral visual field defects. Patients' fine vision is mainly
      affected by central visual field defects, the rehabilitation training for which
      can be divided into eccentric viewing training, eye movement training and
      perceptual learning training. Patients' visual exploration, orientation, walking
      and reading are largely influenced by hemianopia and peripheral visual field
      defects, the rehabilitation training for which can be separated into visual
      restoration strategy and eye movement compensatory strategy. 

PMID- 26310263
TI  - Late onset tic disorder: A rare occurrence.

PMID- 26310261
TI  - Perioperative elafin for ischaemia-reperfusion injury during coronary artery
      bypass graft surgery: a randomised-controlled trial.
AB  - BACKGROUND: Elafin is a potent endogenous neutrophil elastase inhibitor that
      protects against myocardial inflammation and injury in preclinical models of
      ischaemic-reperfusion injury. We investigated whether elafin could inhibit
      myocardial ischaemia-reperfusion injury induced during coronary artery bypass
      graft (CABG) surgery. METHODS AND RESULTS: In a randomised double-blind placebo
      controlled parallel group clinical trial, 87 patients undergoing CABG surgery
      were randomised 1:1 to intravenous elafin 200 mg or saline placebo administered
      after induction of anaesthesia and prior to sternotomy. Myocardial injury was
      measured as cardiac troponin I release over 48 h (area under the curve (AUC)) and
      myocardial infarction identified with MRI. Postischaemic inflammation was
      measured by plasma markers including AUC high-sensitive C reactive protein (hs
      CRP) and myeloperoxidase (MPO). Elafin infusion was safe and resulted in >3000
      fold increase in plasma elafin concentrations and >50% inhibition of elastase
      activity in the first 24 h. This did not reduce myocardial injury over 48 h
      (ratio of geometric means (elafin/placebo) of AUC troponin I 0.74 (95% CI 0.47 to
      1.15, p=0.18)) although post hoc analysis of the high-sensitive assay revealed
      lower troponin I concentrations at 6 h in elafin-treated patients (median 2.4 vs
      4.1 MUg/L, p=0.035). Elafin had no effect on myocardial infarction (elafin, 7/34
      vs placebo, 5/35 patients) or on markers of inflammation: mean differences for
      AUC hs-CRP of 499 mg/L/48 h (95% CI -207 to 1205, p=0.16), and AUC MPO of 238
      ng/mL/48 h (95% CI -235 to 711, p=0.320). CONCLUSIONS: There was no strong
      evidence that neutrophil elastase inhibition with a single-dose elafin treatment
      reduced myocardial injury and inflammation following CABG-induced ischaemia
      reperfusion injury. TRIAL REGISTRATION NUMBER: (EudraCT 2010-019527-58,
      ISRCTN82061264).

PMID- 26310262
TI  - Acute myocardial infarction and influenza: a meta-analysis of case-control
      studies.
AB  - OBJECTIVE: Acute myocardial infarction (AMI) is the leading cause of death and
      disability globally. There is increasing evidence from observational studies that
      influenza infection is associated with AMI. In patients with known coronary
      disease, influenza vaccination is associated with a lower risk of cardiovascular
      events. However, the effect of influenza vaccination on incident AMI across the
      entire population is less well established. METHOD: The purpose of our systematic
      review of case-control studies is twofold: (1) to estimate the association
      between influenza infection and AMI and (2) to estimate the association between
      influenza vaccination and AMI. Cases included those conducted with first-time AMI
      or any AMI cases. Studies were appraised for quality and meta-analyses using
      random effects models for the influenza exposures of infection, and vaccination
      were conducted. RESULTS: 16 studies (8 on influenza vaccination, 10 on influenza
      infection and AMI) met the eligibility criteria, and were included in the review
      and meta-analysis. Recent influenza infection, influenza-like illness or
      respiratory tract infection was significantly more likely in AMI cases, with a
      pooled OR 2.01 (95% CI 1.47 to 2.76). Influenza vaccination was significantly
      associated with AMI, with a pooled OR of 0.71 (95% CI 0.56 to 0.91), equating to
      an estimated vaccine effectiveness of 29% (95% CI 9% to 44%) against AMI.
      CONCLUSIONS: Our meta-analysis of case-control studies found a significant
      association between recent respiratory infection and AMI. The estimated vaccine
      effectiveness against AMI was comparable with the efficacy of currently accepted
      therapies for secondary prevention of AMI from clinical trial data. A large-scale
      randomised controlled trial is needed to provide robust evidence of the
      protective effect of influenza vaccination on AMI, including as primary
      prevention.

PMID- 26310264
TI  - Experiences of discrimination and positive treatment in people with mental health
      problems: Findings from an Australian national survey.
AB  - OBJECTIVE: Stigma and discrimination are central concerns for people with mental
      health problems. The aim of the study was to carry out a national survey in order
      to assess experiences of avoidance, discrimination and positive treatment in
      people with mental health problems. METHODS: In 2014, telephone interviews were
      carried out with 5220 Australians aged 18+, 1381 of whom reported a mental health
      problem or scored highly on a symptom screening questionnaire. Questions covered
      experiences of avoidance, discrimination and positive treatment by friends,
      spouse, other family, workplace, educational institution and others in the
      community. RESULTS: In most domains, respondents reported more positive treatment
      experiences than avoidance or discrimination. Friends and family were more likely
      to avoid the person than to discriminate. CONCLUSION: The results can provide
      input into the design of anti-discrimination interventions and further empower
      people with mental health problems as they advocate for change in the area of
      discrimination.

PMID- 26310265
TI  - Ventricular arrhythmia storm in the era of implantable cardioverter
      defibrillator.
AB  - In the era of widespread use of implantable cardioverter-defibrillators (ICDs)
      for both primary and secondary prevention of sudden cardiac death, a significant
      proportion of patients experience episodes of multiple ventricular
      tachycardia/fibrillation over a short period of time requiring device
      interventions. The episodes are termed ventricular arrhythmia (VA) or electrical
      storms. VA storm is a tragic experience for patients, with many psychological
      consequences. Current management for VA storms remains complex. Acutely,
      administration of beta-blockers, amiodarone and sedation or intubation is
      generally required to suppress sympathetic tone. Interventional treatment
      includes catheter ablation and sympathetic blockade by left cardiac sympathetic
      denervation. Strategies to modify autonomic tone to suppress VAs are the
      rationale of various novel interventions that have been published in recent
      studies. All patients with VA storm should be considered for transfer to an
      experienced high-volume tertiary centre for evaluation and treatment to prevent
      further recurrence of VA storm.

PMID- 26310266
TI  - Puerperal sepsis in the 21st century: progress, new challenges and the situation
      worldwide.
AB  - Puerperal sepsis is one of the five leading causes of maternal mortality
      worldwide, and accounts for 15% of all maternal deaths. The WHO defined puerperal
      sepsis in 1992 as an infection of the genital tract occurring at any time between
      the rupture of membranes or labour and the 42nd day post partum; in which, two or
      more of the following are present: pelvic pain, fever, abnormal vaginal discharge
      and delay in the reduction of the size of the uterus. At the same time, the WHO
      introduced the term puerperal infections, which also include non-genital
      infections in the obstetric population. Recent epidemiological data shows that
      puerperal sepsis and non-genital tract infections are a major area of concern. In
      puerperal sepsis, group A streptococcus (GAS) is the most feared pathogen. Up to
      30% of the population are asymptomatic carriers of GAS. GAS commonly causes
      throat infections. Women who died from GAS-positive sepsis all had signs of a
      throat infection themselves or one of their family members suffered from a throat
      infection. The pathway of infection is from the hands of the pregnant women or
      the mother to her perineum. In non-genital tract infections, influenza viruses
      and the HIV pandemic in the developing part of the world are responsible for many
      maternal deaths, and demand our attention. The physiological changes of pregnancy
      and the puerperium can obscure the signs and symptoms of sepsis in the obstetric
      population. A high level of suspicion is, therefore, needed in the care for the
      sick pregnant patient. If sepsis is suspected, timely administration of
      antibiotics, sepsis care bundles, multidisciplinary discussion and early
      involvement of senior staff members are important to improve outcome. 

PMID- 26310267
TI  - Cost and availability of gluten-free food in the UK: in store and online.
AB  - OBJECTIVE: Coeliac disease (CD) is a lifelong condition requiring strict
      adherence to a gluten-free (GF) diet and good availability of GF foods is
      critical to this. Patients with CD from lower socioeconomic groups are recognised
      to have higher treatment burden and higher food costs may impact this. Therefore,
      we aimed to assess the availability and cost of GF food in supermarkets and via
      the internet. DESIGN: Supermarkets and internet shops delivering to homes in a
      single city (UK) were analysed between February and March 2014. Stores were
      identified with comprehensive internet searches. Ten commonly purchased items
      were analysed for cost and compared with standard non-GF alternatives. Direct
      measurement of the number of GF foods available was compared between stores which
      were categorised according to previously published work. SETTING: Supermarkets
      covering the whole of Sheffield, UK. RESULTS: None of the budget supermarkets
      surveyed stocked any GF foods. Quality and regular supermarkets stocked the
      greatest range, each stocking a median of 22 (IQR 39) items (p<0.0001). All GF
      foods were at least four times more expensive than non-GF alternatives
      (p<0.0001). GF products are prevalent online, but 5/10 of the surveyed products
      were significantly more expensive than equivalents in supermarkets. CONCLUSIONS:
      There is good availability of GF food in regular and quality supermarkets as well
      as online, but it remains significantly more expensive. Budget supermarkets which
      tend to be frequented by patients from lower socioeconomic classes stocked no GF
      foods. This poor availability and added cost is likely to impact on adherence in
      deprived groups.

PMID- 26310268
TI  - Spinal cord oligodendrocyte-derived alarmin IL-33 mediates neuropathic pain.
AB  - Neuropathic pain from injury to the peripheral and CNS represents a major health
      care issue. We have investigated the role of IL-33/IL-33 receptor (ST2) signaling
      in experimental models of neuropathic pain in mice. Chronic constriction injury
      (CCI) of the sciatic nerve induced IL-33 production in the spinal cord. IL
      33/citrine reporter mice revealed that oligodendrocytes are the main cells
      expressing IL-33 within the spinal cord together with a minor expression by
      neurons, microglia. and astrocytes. CCI-induced mechanical hyperalgesia was
      reduced in IL-33R (ST2)(-/ -) mice compared with wild-type (WT) mice. Intrathecal
      treatment of WT mice with soluble IL-33 receptor (IL-33 decoy receptor) markedly
      reduced CCI-induced hyperalgesia. Consistent with these observations, intrathecal
      injection of IL-33 enhanced CCI hyperalgesia and induced hyperalgesia in naive
      mice. IL-33-mediated hyperalgesia during CCI was dependent on a reciprocal
      relationship with TNF-alpha and IL-1beta. IL-33-induced hyperalgesia was markedly
      attenuated by inhibitors of PI3K, mammalian target of rapamycin, MAPKs (p38, ERK,
      and JNK), NF-kappaB, and also by the inhibitors of glial cells (microglia and
      astrocytes). Furthermore, targeting these signaling pathways and cells inhibited
      IL-33-induced TNF-alpha and IL-1beta production in the spinal cord. Our study,
      therefore, reveals an important role of oligodendrocyte-derived IL-33 in
      neuropathic pain.

PMID- 26310269
TI  - Effective disposal of nitrogen waste in blood-fed Aedes aegypti mosquitoes
      requires alanine aminotransferase.
AB  - To better understand the mechanisms responsible for the success of female
      mosquitoes in their disposal of excess nitrogen, we investigated the role of
      alanine aminotransferase (ALAT) in blood-fed Aedes aegypti. Transcript and
      protein levels from the 2 ALAT genes were analyzed in sucrose- and blood-fed A.
      aegypti tissues. ALAT1 and ALAT2 exhibit distinct expression patterns in tissues
      during the first gonotrophic cycle. Injection of female mosquitoes with either
      double-stranded RNA (dsRNA)-ALAT1 or dsRNA ALAT2 significantly decreased mRNA and
      protein levels of ALAT1 or ALAT2 in fat body, thorax, and Malpighian tubules
      compared with dsRNA firefly luciferase-injected control mosquitoes. The silencing
      of either A. aegypti ALAT1 or ALAT2 caused unexpected phenotypes such as a delay
      in blood digestion, a massive accumulation of uric acid in the midgut posterior
      region, and a significant decrease of nitrogen waste excretion during the first
      48 h after blood feeding. Concurrently, the expression of genes encoding xanthine
      dehydrogenase and ammonia transporter (Rhesus 50 glycoprotein) were significantly
      increased in tissues of both ALAT1- and ALAT2-deficient females. Moreover,
      perturbation of ALAT1 and ALAT2 in the female mosquitoes delayed oviposition and
      reduced egg production. These novel findings underscore the efficient mechanisms
      that blood-fed mosquitoes use to avoid ammonia toxicity and free radical damage.
      Mazzalupo, S., Isoe, J., Belloni, V., Scaraffia, P. Y. Effective disposal of
      nitrogen waste in blood-fed Aedes aegypti mosquitoes requires alanine
      aminotransferase. 

PMID- 26310271
TI  - Evaluation of Molecular and Immunohistochemical Adjunct Modalities in the
      Diagnosis of Soft Tissue Neoplasms.
AB  - The accurate diagnosis of soft tissue neoplasms has crucial therapeutic and
      prognostic importance. There is frequent morphologic overlap between entities,
      and ancillary modalities are used in the vast majority of diagnoses.
      Immunohistochemistry is rapid and inexpensive, and in addition to the older
      markers that mainly detected cytoplasmic proteins, antibodies can indirectly
      detect tumor-specific genetic and molecular abnormalities. The use of molecular
      diagnostic techniques is now widespread, with molecular services often integrated
      into routine histopathology laboratories; as their cost and turnaround times
      begin to parallel those for immunohistochemistry, we compared the usefulness of
      ancillary immunohistochemistry, molecular genetic, and molecular cytogenetic
      techniques in the diagnosis of soft tissue lesions. We evaluated the number and
      contribution of immunohistochemical tests and panels and of ancillary molecular
      techniques in the primary histopathologic diagnosis of 150 soft tissue lesions.
      Ninety of 150 cases required either only one immunohistochemical panel or minimal
      immunohistochemistry for diagnosis, while 39/150 required 2 to 4 panels. In
      5/150, ancillary molecular tests alone (without immunohistochemistry) were
      diagnostically sufficient. The majority of cases required one immunohistochemical
      panel for diagnosis, with a smaller proportion requiring a second, and a minority
      requiring a third or fourth (which mainly comprised neoplasms for which the final
      diagnosis was uncertain). Certain neoplasms required both extensive
      immunohistochemistry and ancillary molecular testing, despite which the final
      diagnosis was inconclusive. Ancillary molecular techniques now make a significant
      contribution to soft tissue tumor diagnosis, being required in over one third
      (52/150) of cases, and were useful in confirming or excluding tumors that were
      not possible to conclusively diagnose with histology and immunohistochemistry.
      Only a small proportion of soft tissue neoplasms (16/150; all benign) did not
      require immunohistochemistry or ancillary molecular methods, with morphology
      alone being sufficient for diagnosis. 

PMID- 26310272
TI  - "Russell Body Gastroenterocolitis" in a Posttransplant Patient: A Case Report and
      Review of Literature.
AB  - Russell bodies represent a cellular response to overstimulation of plasma cells,
      leading to the accumulation of abundant, nondegradable, condensed immunoglobulin
      in dilated rough endoplasmic reticulum cisternae. Russell body gastritis was
      first described 1998 by Tazawa and Tsutsumi. Since then only 39 cases involving
      the gastrointestinal tract have been reported in English literature, which
      include Russell body gastritis, duodenitis, and esophagitis. We report a case of
      a 44-year-old female with a history of diabetes mellitus, status post kidney and
      pancreas transplant who presented with multiple episodes of watery diarrhea
      associated with abdominal pain, nausea, and vomiting. Upper gastroendoscopic
      examination showed diffuse mild erythema in the gastric body and a clean-based
      duodenal ulcer. Lower gastroendoscopic examination was normal. Examination of
      multiple biopsies from duodenal, gastric, terminal ileum, and colonic mucosae
      revealed numerous plasma cells with abundant eosinophilic granular cytoplasm
      (Russell bodies) and eccentric nuclei, highlighted by PAS stain and CD 138 plasma
      cell marker. Helicobacter pylori stains were performed on gastric biopsies and
      were negative for organisms. To date, there are no cases described in English
      literature with multifocal Russell body infiltrates in gastrointestinal tract in
      a single patient including ileum and/or colon. This makes our case the first to
      be reported with these unique findings; thus, the spectrum of Russell body
      associated chronic inflammation of the gastrointestinal tract would be more
      suitably referred to as "Russell body gastroenterocolitis." 

PMID- 26310270
TI  - Talin1 is required for cardiac Z-disk stabilization and endothelial integrity in
      zebrafish.
AB  - Talin (tln) binds and activates integrins to couple extracellular matrix-bound
      integrins to the cytoskeleton; however, its role in heart development is not well
      characterized. We identified the defective gene and the resulting cardiovascular
      phenotypes in zebrafish tln1(fl02k) mutants. The ethylnitrosourea-induced fl02k
      mutant showed heart failure, brain hemorrhage, and diminished cardiac and vessel
      lumens at 52 h post fertilization. Positional cloning revealed a nonsense
      mutation of tln1 in this mutant. tln1, but neither tln2 nor -2a, was dominantly
      expressed in the heart and vessels. Unlike tln1 and -2 in the mouse heart, the
      unique tln1 expression in the heart enabled us, for the first time, to determine
      the critical roles of Tln1 in the maintenance of cardiac sarcomeric Z-disks and
      endothelial/endocardial cell integrity, partly through regulating F-actin
      networks in zebrafish. The similar expression profiles of tln1 and integrin
      beta1b (itgb1b) and synergistic function of the 2 genes revealed that itgb1b is a
      potential partner for tln1 in the stabilization of cardiac Z-disks and vessel
      lumens. Taken together, the results of this work suggest that Tln1-mediated
      Itgbeta1b plays a crucial role in maintaining cardiac sarcomeric Z-disks and
      endothelial/endocardial cell integrity in zebrafish and may also help to gain
      molecular insights into congenital heart diseases.

PMID- 26310273
TI  - Myopia in young patients with type 1 diabetes mellitus.
AB  - INTRODUCTION: This study aimed to evaluate the proportion of young patients with
      type 1 diabetes mellitus (T1DM) who have myopia, as well as the risk factors
      associated with myopia in this group. METHODS: In this cross-sectional study,
      patients aged < 21 years with T1DM for >= 1 year underwent a comprehensive eye
      examination. Presence of parental myopia, and average hours of near-work and
      outdoor activity were estimated using a questionnaire. Annualised glycosylated
      haemoglobin (HbA1c), defined as the mean of the last three HbA1c readings taken
      over the last year, was calculated. Multivariate analysis using genetic,
      environmental and diabetes-related factors was done to evaluate risk factors
      associated with myopia. RESULTS: Of the 146 patients (mean age 12.5 +/- 3.6
      years) recruited, 66.4% were Chinese and 57.5% were female. Myopia (i.e.
      spherical equivalent [SE] of -0.50 D or worse) was present in 96 (65.8%)
      patients. The proportion of patients with myopia increased from 25.0% and 53.6%
      in those aged < 7.0 years and 7.0-9.9 years, respectively, to 59.2% and 78.4% in
      those aged 10.0-11.9 years and >= 12.0 years, respectively. Higher levels of SE
      were associated with lower parental myopia (p = 0.024) and higher annualised
      HbA1c (p = 0.011). CONCLUSION: Compared to the background population, the
      proportion of myopia in young patients with T1DM was higher in those aged < 10
      years but similar in the older age group. Myopia was associated with a history of
      parental myopia. Environmental risk factors and poor glycaemic control were not
      related to higher myopia risk.

PMID- 26310274
TI  - Downregulation of ubiquitin-associated protein 2-like with a short hairpin RNA
      inhibits human glioma cell growth in vitro.
AB  - Ubiquitin-associated protein 2-like (UBAP2L), which contains a ubiquitin
      associated (UBA) domain near its N-terminus, has been indicated in the
      pathogenesis of several human cancers, including multiple myeloma, hepatocellular
      carcinoma and malignant ovarian tumors. However, the role of UBAP2L in human
      glioma remains unknown. In the present study, UBAP2L was widely expressed in
      multiple glioma cell lines. To further examine the effects of UBAP2L on glioma
      growth, lentivirus-mediated short hairpin RNA (shRNA) was employed to knockdown
      UBAP2L expression in the glioblastoma cell lines. Depletion of UBAP2L
      significantly inhibited the proliferation and colony formation ability, as
      determined by MTT and colony formation assays. Cell cycle analysis showed that
      UBAP2L knockdown induced G0/G1 phase arrest in U251 and U373 cells, while S phase
      arrest was induced in A172 cells. These results suggest that UBAP2L has a key
      role in glioma cell growth, and may act as an oncogene to promote malignant
      glioma development. 

PMID- 26310275
TI  - CRP 1846C>T Genetic Polymorphism Is Associated with Lymph Node Metastasis and/or
      Severe Lymphatic Invasion in Endometrial Cancer.
AB  - Endometrial cancer (EC) rates are rising in Japan. Lymph node (LN) metastasis is
      an important prognostic factor in EC, and its risk is increased with higher tumor
      grade, deep myometrial invasion, larger tumor size, and lymphovascular space
      invasion (LVSI). Current methodologies to assess these factors are unreliable. We
      previously showed the association between C-reactive protein (CRP) 1846C>T
      (rs1205) polymorphism and LN metastasis in esophageal, non-small cell lung, and
      breast cancers. The CRP gene is located on chromosome 1q21-q23, and the
      polymorphism in the noncoding region (1846C>T) of this gene decreases serum CRP
      levels. We investigated the relationship between CRP 1846C>T genetic polymorphism
      and LN metastasis or LVSI in 130 EC patients using polymerase chain reaction
      restriction fragment length polymorphism. The CRP 1846C/T genotype was C/C in 11
      patients, C/T in 58 patients and T/T in 61 patients. The patients were divided
      into two groups based on their CRP 1846 genotypes: "C/C" and "C/T + T/T". Nine
      (7%) and 18 (13%) patients, all with the polymorphism, had LN metastasis and
      moderate or prominent lymphatic invasion, respectively. LN metastasis and/or
      severe lymphatic invasion were observed in the C/T + T/T group, while patients
      with the C/C genotype had no LN metastases or severe lymphatic invasion.
      Univariate and multivariate logistic regression models revealed that the C/T +
      T/T patients had a significant likelihood of developing LN metastasis and/or
      severe lymphatic invasion. Our results suggest that CRP genetic polymorphism is a
      novel risk predictor of LN metastasis and/or lymphatic invasion in EC. 

PMID- 26310276
TI  - Neutrophil-macrophage interplay in atherosclerosis: protease-mediated cytokine
      processing versus NET release.

PMID- 26310277
TI  - Using the Internet to Support Exercise and Diet: A Stratified Norwegian Survey.
AB  - BACKGROUND: Internet is used for a variety of health related purposes. Use
      differs and has differential effects on health according to socioeconomic status.
      OBJECTIVE: We investigated to what extent the Norwegian population use the
      Internet to support exercise and diet, what kind of services they use, and
      whether there are social disparities in use. We expected to find differences
      according to educational attainment. METHODS: In November 2013 we surveyed a
      stratified sample of 2196 persons drawn from a Web panel of about 50,000
      Norwegians over 15 years of age. The questionnaire included questions about using
      the Internet, including social network sites (SNS), or mobile apps in relation to
      exercise or diet, as well as background information about education, body image,
      and health. The survey email was opened by 1187 respondents (54%). Of these, 89
      did not click on the survey hyperlink (declined to participate), while another 70
      did not complete the survey. The final sample size is thus 1028 (87% response
      rate). Compared to the Norwegian census the sample had a slight under
      representation of respondents under the age of 30 and with low education. The
      data was weighted accordingly before analyses. RESULTS: Sixty-nine percent of
      women and 53% of men had read about exercise or diet on the Internet (chi(2)=
      25.6, P<.001). More people with higher education (71%, chi(2)=19.1, P<.001),
      reported this. The same gender difference was found for using Internet-based
      interventions with 20% of women compared to14% of men reporting having used these
      interventions (chi(2)=7.9, P= .005), for having posted a status about exercise or
      diet on Facebook or other SNS (23% vs 12%, chi(2)=18.8, P<.001), and for having
      kept an online exercise or diet journal (21% vs 15%, chi(2)=7.0, P=.008).
      Evaluations of own physical appearance accounted for some of the gender
      differences in using online exercise or diet journals. Seven percent of the total
      sample reported having used electronic communication to ask professionals about
      exercise or diet, while a few more had discussed online with peers (10%). Asking
      professionals online was more common amongst those with only primary education
      (13%, chi(2)<10.5, P=.005).  CONCLUSIONS: Gender and education are related to how
      the Internet is used to support health behaviors. We should be aware of the
      potential role of the Internet in accelerating social disparities in health, and
      continue to monitor population use. For Internet- and mobile-based interventions
      to support health behaviors, this study provides information relevant to
      tailoring of delivery media and components to user.

PMID- 26310278
TI  - Skin Biopsy, the Allergists' Tool: How to Interpret a Report.
AB  - Inflammatory dermatoses are frequently encountered by the allergist, and
      histologic evaluation achieved through skin biopsy can be of tremendous value
      clinically. There is no substitute for a thorough history and physical exam;
      however, the skin biopsy is a simple, in-office procedure with little risk of
      complication that can provide invaluable information when a diagnosis is
      uncertain. Histopathologically, many inflammatory eruptions can look similar or
      overlap, but information provided by the dermatopathologist can help the
      clinician render or refine the clinical diagnosis and guide management. This
      review will discuss descriptive elements contained in the pathology report to
      provide a framework that can be used by the allergist to comfortably and
      confidently diagnose inflammatory dermatologic conditions. 

PMID- 26310279
TI  - A Population-Based Examination of the Surgical Outcomes for Patients with
      Esophageal Sarcoma.
AB  - BACKGROUND: Esophageal sarcoma (ES) is a rare malignancy. The literature is
      limited to small case series and reports. This study used a population data set
      to study the characteristics, treatments, surgical outcomes, and prognostic
      factors for survival among ES patients. METHODS: The study identified 178 ES
      cases (0.3 %) and 63,548 esophageal carcinoma (EC) cases (99.7 %) including
      adenocarcinoma and squamous cell carcinoma using the Surveillance, Epidemiology,
      and End Results (SEER) Registry (1973-2011). Characteristics and therapeutics
      were compared between ES and EC. Survival data were analyzed using Kaplan-Meier
      estimation. Uni- and multivariate Cox proportional hazard models determined
      predictors of 5-year overall survival (OS). RESULTS: Compared with the EC
      patients, the ES patients were more likely to be women, to have localized tumors,
      and to undergo surgery but less likely to receive radiation (p < 0.001). The most
      common histologies were carcinosarcoma, leiomyosarcoma, and gastrointestinal
      stromal tumor (GIST). The 5-year OS for the ES patients was 38 % compared with 17
      % for the EC patients (p < 0.001). The median survival period for the ES and EC
      surgical patients with locoregional disease was respectively 50 and 24 months.
      The ES patients with nonmetastatic disease who received surgery had better OS
      than those who did not (37 vs. 14 %; p < 0.0001). In the multivariate analysis,
      age and advanced stage conferred worse OS, whereas GIST histology and surgery
      were favorable predictors for OS. CONCLUSION: The ES patients were more likely to
      have localized disease, to be treated with surgery, and to have better OS than
      the EC patients. The survival benefit of surgery suggests that surgery should be
      the primary treatment for ES patients with resectable disease, particularly those
      with GIST.

PMID- 26310280
TI  - Impact of Consensus Guidelines by the Society of Surgical Oncology and the
      American Society for Radiation Oncology on Margins for Breast-Conserving Surgery
      in Stages 1 and 2 Invasive Breast Cancer.
AB  - BACKGROUND: This study aimed to evaluate the impact that the release of consensus
      guidelines for margins in breast-conserving surgery (BCS) had on re-excision
      rates. METHODS: A retrospective review examined a prospectively maintained
      database of patients who had operable invasive breast cancer treated with BCS at
      the authors' institution. The patients were divided into two groups: (1) those
      with a diagnosis determined from 1 July 2011 to 31 July 2013 (before release of
      the guidelines) and (2) those with a diagnosis determined from 1 February 2014 to
      31 July 2014 (after release of the guidelines). The groups were evaluated with
      respect to patient and tumor characteristics, re-excision rates, and reasons for
      re-excision. RESULTS: A total of 846 cases of BCS were managed: 597 in group 1
      and 249 in group 2. Re-excision rates were significantly reduced after release of
      the consensus guidelines (p = 0.03). Re-excisions were performed for 115 (19 %)
      of 597 patients in group 1 and 32 (13 %) of 249 patients in group 2. After
      release of the guidelines, re-excisions were performed for positive margins, as
      defined by the consensus statement, in 25 (78 %) of 32 cases. The two groups did
      not differ significantly in terms of age, tumor size, grade, nodal status,
      estrogen receptor status, progesterone receptor status, or human epidermal growth
      factor receptor 2 status. Group 1 had more tumors of mixed ductal and lobular
      histology than group 2, and group 2 had more lobular tumors than group 1 (p =
      0.02). CONCLUSIONS: The consensus guidelines on margins for BCS were applied for
      78 % of the patients who underwent re-excision and resulted in a significant
      reduction in re-excision rates.

PMID- 26310281
TI  - Nuclear PROX1 is Associated with Hypoxia-Inducible Factor 1alpha Expression and
      Cancer Progression in Esophageal Squamous Cell Carcinoma.
AB  - BACKGROUND: Transcription factor prospero homeobox 1 (PROX1) has been identified
      as a master regulator of lymphangiogenesis associated with metastasis. Although
      PROX1 expression has been investigated in several cancers, its clinical
      significance remains controversial and needs further validation. In this study,
      we investigated the clinical and functional significance of PROX1 and PROX1
      regulator hypoxia-inducible factor 1alpha (HIF1alpha) in esophageal squamous cell
      carcinoma (ESCC). METHODS: A total of 117 samples from ESCC patients were
      analyzed for PROX1, HIF1alpha, and E-cadherin expression by immunohistochemistry;
      correlation with clinicopathological characteristics was determined. PROX1
      function was evaluated in PROX1 small interfering RNA (siRNA)-transfected human
      ESCC cells in vitro by assessing cell proliferation and migration. RESULTS: PROX1
      expression was higher in ESCC than in normal tissues. Patients with higher PROX1
      expression (n = 26) had increased nuclear accumulation of HIF1alpha (p = 0.004)
      and more advanced metastasis, both lymph node (N factor; p = 0.09) and
      hematogenous (M factor; p = 0.04), than those with lower PROX1 expression (n =
      91). In addition, high PROX1 and HIF1alpha expression correlated with low levels
      of E-cadherin, an epithelial cell marker. Analysis of overall and cancer-specific
      survival indicated that elevated PROX1 expression was significantly correlated
      with poor prognosis (p = 0.0064). PROX1 downregulation in ESCC cells inhibited
      cellular proliferation and migration (p < 0.05). Hypoxia restored PROX1 levels
      that were reduced by PROX1-specific siRNA. CONCLUSION: Our data suggest that high
      expression of PROX1 in ESCC could be used as an indicator of poor prognosis, and
      that PROX1 is a promising candidate molecular target for ESCC treatment.

PMID- 26310282
TI  - Reply to: Fatih Canan "The relationship between internet addiction and eating
      disorders".

PMID- 26310283
TI  - Concurrent validity of the PROMIS(r) pediatric global health measure.
AB  - PURPOSE: To evaluate the concurrent validity of the PROMIS Pediatric Global
      Health measure (PGH-7), child-report and parent-proxy versions. METHODS: Surveys
      were administered via home computer on two separate occasions (December, 2011 and
      August/September, 2012) to a convenience sample of 4636 children 8-17 years old
      and 2609 parents who participated in a national Internet panel. Data analysis
      included: (1) evaluations of differences in PGH-7 scores between groups defined
      by sociodemographics, clinical characteristics, and access to health care; (2)
      associations with 15 PROMIS pediatric measures; and (3) correlations with two
      health-related quality-of-life instruments, the KIDSCREEN-10 and PedsQL-15.
      RESULTS: PGH-7 scores were lower for children with chronic conditions, Hispanic
      ethnicity, low socioeconomic status, and barriers to accessing health care. The
      PGH-7 showed excellent convergent and discriminant validity with PROMIS pediatric
      measures of physical, mental, and social health. The PGH-7 was strongly
      correlated with the KIDSCREEN-10, which assesses positive health, and moderately
      correlated with the PedsQL-15, which assesses problems with a child's health.
      CONCLUSIONS: The PGH-7 measures global health, summarizing a child's physical,
      mental, and social health into a single score. These properties make it a useful
      clinical, population health, and research tool for applications that require an
      efficient, precise, and valid summary measure of a children's self-reported
      health status. Future research should prospectively evaluate the PGH-7's capacity
      to detect change that results from alterations in clinical status,
      transformations of the healthcare delivery system, and children's health
      development.

PMID- 26310284
TI  - Smoking status and health-related quality of life: a longitudinal study in young
      adults.
AB  - PURPOSE: The possibility that tobacco use affects health-related quality of life
      (HRQoL) has attracted interest. However, a lack of prospective evidence weakens
      the case for a causal relationship. The aim was to examine the longitudinal
      relationship between change in smoking status and change in HRQoL in young
      adults. METHODS: We conducted a population-based cohort study with data collected
      in 2004-2006 (aged 26-36) and 2009-2011 (aged 31-41). Exposure was change in self
      reported smoking status during follow-up. Outcomes were changes in physical and
      mental HRQoL measured by SF-12. RESULTS: For physical HRQoL (n = 2080), quitters
      had a 2.12 (95 % confidence interval (CI) 0.73, 3.51) point improvement than
      continuing smokers, whereas former smokers who resumed smoking had a 2.08 (95 %
      CI 0.21, 3.94) point reduction than those who maintained cessation. Resumed
      smokers were 39 % (95 % CI 10, 75 %) more likely to have a clinically significant
      (>5 point) reduction of physical HRQoL than former smokers who maintained
      cessation. In contrast, quitters were 43 % (95 % CI 3, 98 %) more likely to have
      a clinically significant (>5 point) improvement in physical HRQoL than continuing
      smokers. Change in smoking status was not significantly associated with change in
      mental HRQoL (n = 1788). CONCLUSIONS: Smoking by young adults was cross
      sectionally associated with lower physical HRQoL and longitudinally associated
      with reductions in physical HRQoL. The expectation of short- to medium-term gains
      in physical HRQoL as well as long-term health benefits may help motivate young
      adult smokers to quit.

PMID- 26310285
TI  - Whole-brain radiation fails to boost intracerebral gefitinib concentration in
      patients with brain metastatic non-small cell lung cancer: a self-controlled,
      pilot study.
AB  - PURPOSE: Whole-brain radiation therapy (WBRT) is generally considered as an
      efficient strategy to improve blood-brain barrier (BBB) permeability by damaging
      BBB structure and is therefore, used as a promising pretreatment of chemotherapy.
      However, the impact of radiotherapy on leaky BBB is still controversial for the
      reason that BBB of metastatic brain tumor lesion had been breached by tumor
      metastasizing. Herein, we conducted a self-controlled study to evaluate the
      effect of WBRT on the permeability of BBB in non-small cell lung cancer (NSCLC)
      patients with brain metastases (BM). METHOD: A prospective self-controlled
      research was performed. Radiation-naive NSCLC patients with BM were enrolled and
      treated with gefitinib for 2 weeks, and then concurrently combined with WBRT for
      2 weeks. Plasma and cerebrospinal fluid (CSF) before and after WBRT were
      collected on day 15 and 29 after the initiation of gefitinib treatment. The
      concentrations of gefitinib in these samples were measured by HPLC. RESULTS:
      Three patients were enrolled and evaluated. The concentrations of gefitinib in
      plasma and CSF pre-WBRT were comparable to those of post-WBRT. Consequently, no
      significant change was noted in the CSF-to-plasma ratios of gefitinib before and
      after WBRT (2.79 +/- 1.47 vs. 2.35 +/- 1.74 %, p = 0.123). CONCLUSIONS: The WBRT
      may not affect the BBB permeability by determining the concentration of gefitinib
      in NSCLC patients with BM.

PMID- 26310286
TI  - Surgical Treatment of Dextroversion, Isolated Persistent Left Superior Vena Cava
      Draining Into the Left Atrium.
AB  - We report a rare case of dextroversion accompanied with atrial septal defect
      (ASD), persistent left superior vena cava with absent right superior vena cava in
      a four-year-old male. A polytetrafluoroethylene (PTFE) graft as an extracardiac
      conduit was used to connect the persistent left superior vena cava (PLSVC) with
      the right atrial appendage.

PMID- 26310287
TI  - Creation of a cerebellar diameter reference standard and its clinical application
      to the detection of cerebellar hypoplasia unique to trisomy 18.
AB  - AIM: We created a new reference standard focusing on the hemispheric
      anteroposterior cerebellar diameter (APCD) in addition to the transverse
      cerebellar diameter (TCD) and discussed whether or not the cerebellar measurement
      was useful for the detection of trisomy 18 (T18). MATERIAL AND METHODS: In 150
      normal fetuses between 14 and 36 weeks of gestational age (GA), the TCD and APCD
      were prospectively measured. In 26 cases with T18, the value was compared with
      the control. RESULTS: At <22 weeks of gestation, the TCD reference standard was
      calculated as follows: TCD = (1.027 * GA) - 0.674 (R(2) = 0.97, P < 0.001). The
      reference standard of the APCD was calculated as follows: APCD = (0.682 * GA) -
      3.925 (R(2) = 0.73, P < 0.001). In eight cases with T18, the TCD was below the
      5th percentile value in 7/8 (88%) cases and the APCD was below the 5th percentile
      value in 8/8 (100%) cases. At >22 weeks of gestation, the reference standard of
      the TCD was calculated as follows: TCD = (1.603 * GA) - 13.216 (R(2) = 0.92, P <
      0.001). The reference standard of the APCD was calculated as follows: APCD =
      (0.859 * GA) - 7.30 (R(2) = 0.84, P < 0.001). In 18 cases with T18, the TCD was
      below the 5th percentile value in 14/18 (78%) cases and the APCD was below the
      5th percentile value in 18/18 (100%) cases. CONCLUSION: APCD reference standard,
      divided by the gestational age of more or less than 22 weeks, might be useful to
      diagnose T18.

PMID- 26310288
TI  - Estimating the population local wavelet spectrum with application to non
      stationary functional magnetic resonance imaging time series.
AB  - Functional magnetic resonance imaging (fMRI) is a dynamic four-dimensional
      imaging modality. However, in almost all fMRI analyses, the time series elements
      of this data are assumed to be second-order stationary. In this paper, we
      examine, using time series spectral methods, whether such stationary assumptions
      can be made and whether estimates of non-stationarity can be used to gain
      understanding into fMRI experiments. A non-stationary version of replicated
      stationary time series analysis is proposed that takes into account the
      replicated time series that are available from nearby voxels in a region of
      interest (ROI). These are used to investigate non-stationarities in both the ROI
      itself and the variations within the ROI. The proposed techniques are applied to
      simulated data and to an anxiety-inducing fMRI experiment.

PMID- 26310289
TI  - A systematic review and meta-analysis of randomized controlled trials of
      endovascular thrombectomy compared with best medical treatment for acute ischemic
      stroke.
AB  - BACKGROUND: Acute ischemic strokes involving occlusion of large vessels usually
      recanalize poorly following treatment with intravenous thrombolysis. Recent
      studies have shown higher recanalization and higher good outcome rates with
      endovascular therapy compared with best medical management alone. A systematic
      review and meta-analysis investigating the benefits of all randomized controlled
      trials of endovascular thrombectomy where at least 25% of patients were treated
      with a thrombectomy device for the treatment of acute ischemic stroke compared
      with best medical treatment have yet to be performed. AIM: To perform a
      systematic review and a meta-analysis evaluating the effectiveness of
      endovascular thrombectomy compared with best medical care for treatment of acute
      ischemic stroke. SUMMARY OF REVIEW: Our search identified 437 publications, from
      which eight studies (totaling 2423 patients) matched the inclusion criteria.
      Overall, endovascular thrombectomy was associated with improved functional
      outcomes (modified Rankin Scale 0-2) [odds ratio 1.56 (1.32-1.85), P < 0.00001].
      There was a tendency toward decreased mortality [odds ratio 0.84 (0.67-1.05), P =
      0.12], and symptomatic intracerebral hemorrhage was not increased [odds ratio
      1.03 (0.71-1.49), P = 0.88] compared with best medical management alone. The odds
      ratio for a favorable functional outcome increased to 2.23 (1.77-2.81, P <
      0.00001) when newer generation thrombectomy devices were used in greater than 50%
      of the cases in each trial. CONCLUSIONS: There is clear evidence for improvement
      in functional independence with endovascular thrombectomy compared with standard
      medical care, suggesting that endovascular thrombectomy should be considered the
      standard effective treatment alongside thombolysis in eligible patients.

PMID- 26310291
TI  - Functionalization of Carbonaceous Nanodots from Mn(II) -Coordinating Functional
      Knots.
AB  - Transition metal (TM)-induced functionalization has been expected to be powerful
      for the modification of carbonaceous nanodots (CDs) for many years. Although some
      attempts have been made, relevant research evolutions are at a standstill. In
      this work, a coordination-carbonization protocol to gain Mn(II) -functionalized
      CDs (MCDs) was innovatively employed, and the modification of CDs based on metal
      coordinating functional knots was realized. By investigating the structural and
      photophysical properties, coordinating conformation of functional knots was
      confirmed and considered to be correlated with excitation-independent
      photoluminescence as well as large Stokes shift of MCDs. Moreover, potential
      applications of MCDs have been extended from common bioimaging and fluorescent
      inks to new areas, such as chemosensors for volatile organic compounds and
      anticorrosion fluorescent films. 

PMID- 26310290
TI  - Anther and pollen development: A conserved developmental pathway.
AB  - Pollen development is a critical step in plant development that is needed for
      successful breeding and seed formation. Manipulation of male fertility has proved
      a useful trait for hybrid breeding and increased crop yield. However, although
      there is a good understanding developing of the molecular mechanisms of anther
      and pollen anther development in model species, such as Arabidopsis and rice,
      little is known about the equivalent processes in important crops. Nevertheless
      the onset of increased genomic information and genetic tools is facilitating
      translation of information from the models to crops, such as barley and wheat;
      this will enable increased understanding and manipulation of these pathways for
      agricultural improvement.

PMID- 26310292
TI  - Self-assembled DNA nanoclews for the efficient delivery of CRISPR-Cas9 for genome
      editing.
AB  - CRISPR-Cas9 represents a promising platform for genome editing, yet means for its
      safe and efficient delivery remain to be fully realized. A novel vehicle that
      simultaneously delivers the Cas9 protein and single guide RNA (sgRNA) is based on
      DNA nanoclews, yarn-like DNA nanoparticles that are synthesized by rolling circle
      amplification. The biologically inspired vehicles were efficiently loaded with
      Cas9/sgRNA complexes and delivered the complexes to the nuclei of human cells,
      thus enabling targeted gene disruption while maintaining cell viability. Editing
      was most efficient when the DNA nanoclew sequence and the sgRNA guide sequence
      were partially complementary, offering a design rule for enhancing delivery.
      Overall, this strategy provides a versatile method that could be adapted for
      delivering other DNA-binding proteins or functional nucleic acids. 

PMID- 26310294
TI  - Solid-phase synthesis of graphene quantum dots from the food additive citric acid
      under microwave irradiation and their use in live-cell imaging.
AB  - The work demonstrated that solid citric acid, one of the most common food
      additives, can be converted to graphene quantum dots (GQDs) under microwave
      heating. The as-prepared GQDs were further characterized by various analytical
      techniques like transmission electron microscopy, atomic force microscopy, X-ray
      diffraction, X-ray photoelectron spectroscopy, Fourier transform infrared
      spectroscopy, fluorescence and UV-visible spectroscopy. Cytotoxicity of the GQDs
      was evaluated using HeLa cells. The result showed that the GQDs almost did not
      exhibit cytotoxicity at concentrations as high as 1000 ug mL(-1). In addition, it
      was found that the GQDs showed good solubility, excellent photostability, and
      excitation-dependent multicolor photoluminescence. Subsequently, the multicolor
      GQDs were successfully used as a fluorescence light-up probe for live-cell
      imaging.

PMID- 26310293
TI  - Defects in tRNA Anticodon Loop 2'-O-Methylation Are Implicated in Nonsyndromic X
      Linked Intellectual Disability due to Mutations in FTSJ1.
AB  - tRNA modifications are crucial for efficient and accurate protein synthesis, and
      modification defects are frequently associated with disease. Yeast trm7Delta
      mutants grow poorly due to lack of 2'-O-methylated C32 (Cm32 ) and Gm34 on
      tRNA(Phe) , catalyzed by Trm7-Trm732 and Trm7-Trm734, respectively, which in turn
      results in loss of wybutosine at G37 . Mutations in human FTSJ1, the likely TRM7
      homolog, cause nonsyndromic X-linked intellectual disability (NSXLID), but the
      role of FTSJ1 in tRNA modification is unknown. Here, we report that tRNA(Phe)
      from two genetically independent cell lines of NSXLID patients with loss-of
      function FTSJ1 mutations nearly completely lacks Cm32 and Gm34 , and has reduced
      peroxywybutosine (o2yW37 ). Additionally, tRNA(Phe) from an NSXLID patient with a
      novel FTSJ1-p.A26P missense allele specifically lacks Gm34 , but has normal
      levels of Cm32 and o2yW37 . tRNA(Phe) from the corresponding Saccharomyces
      cerevisiae trm7-A26P mutant also specifically lacks Gm34 , and the reduced Gm34
      is not due to weaker Trm734 binding. These results directly link defective 2'-O
      methylation of the tRNA anticodon loop to FTSJ1 mutations, suggest that the
      modification defects cause NSXLID, and may implicate Gm34 of tRNA(Phe) as the
      critical modification. These results also underscore the widespread conservation
      of the circuitry for Trm7-dependent anticodon loop modification of eukaryotic
      tRNA(Phe) . 

PMID- 26310298
TI  - Epidemiology and definition of inappropriate sinus tachycardia.
AB  - Inappropriate sinus tachycardia (IST) is a clinical syndrome lacking formal
      diagnostic criteria. It is generally defined as an elevated resting heart rate
      (HR; >90-100 bpm) with an exaggerated response to physical or emotional stress
      and a clearly sinus mechanism. Clinical manifestations are broad from a complete
      lack of symptoms to incapacitating incessant tachycardia. Now understood to be
      relatively prevalent, it is observed to have a generally benign prognosis, though
      symptoms may persist for years. Whether IST is a single discrete entity or a
      heterogeneous condition with overlap to other syndromes such as postural
      orthostatic tachycardia syndrome remains a matter of debate. 

PMID- 26310299
TI  - Catheter ablation of inappropriate sinus tachycardia.
AB  - Catheter ablation for inappropriate sinus tachycardia (IST) is recommended for
      patients symptomatic for palpitations and refractory to other treatments. The
      current approach consists in sinus node modification (SNM), achieved by ablation
      of the cranial part of the sinus node to eliminate faster sinus rates while
      trying to preserve chronotropic competence. This approach has a limited efficacy,
      with a very modest long-term clinical success. To overcome this, proper patient
      selection is crucial and an epicardial approach should always be considered. This
      brief review will discuss the current role and limitations of catheter ablation
      in the management of patients with IST. 

PMID- 26310300
TI  - Phased multipolar radiofrequency pulmonary vein isolation is as effective and
      safe as conventional irrigated point-to-point ablation. A prospective randomised
      1-year implantable cardiac monitoring device follow-up trial.
AB  - PURPOSE: Pulmonary vein isolation (PVI) is conventionally performed using 3D
      electroanatomical mapping to guide point-to-point ablation. The Pulmonary Vein
      Ablation Catheter (PVAC)(r) is a phased multipolar ablation (PMRA) catheter
      designed for rapid PVI using radiological anatomical information. Comparison of
      these methods of PVI using continuous beat-to-beat monitoring was undertaken.
      METHODS: Fifty patients with drug-refractory, symptomatic paroxysmal atrial
      fibrillation (PAF) were recruited. Patients all had REVEAL(r) XT ILR or a DDDRP
      permanent pacemaker (PPM) inserted prior to PVI. PPM was programmed to monitoring
      mode (ODO). Patients were randomised 1:1 to undergo PVI with either point-to
      point irrigated radiofrequency ablation (Conv) or PMRA technology. Follow-up was
      performed at 0, 3, 6, 9, and 12 months using Holter downloads to assess
      arrhythmia burden. Outcomes were examined following a 3-month blanking period.
      RESULTS: The AF burden pre-ablation, at 3-month and at 12-month post-ablations,
      was not significantly different (pre-ablation AF burdens (mean +/- SE) Conv 16.6
      +/- 5.0%, PVAC 17.0 +/- 5.6 %, 3 months Conv 4.0 +/- 1.6 %, PVAC 4.7 +/- 1.5%, 12
      months Conv 4.3 +/- 2.3%, PVAC 3.8 +/- 1.5%). In both groups, there was a
      significant reduction in AF burden from pre-ablation (at 3 months p = 0.01, p =
      0.04, at 12 months p = 0.04, p = 0.03 for Conv and PMRA groups, respectively).
      Overall success rate for zero AF recurrence at 12 months was 54%. CONCLUSION:
      PMRA PVI is comparable to conventional technology for AF extinction at 1 year.
      The PMRA is as safe as conventional technology but enables the operator to
      perform the procedure faster. Device monitored success rates were lower than
      other studies not utilising such intensive monitoring confirming that sporadic
      ECG monitoring is not sufficient to detect all AF recurrence. TRIAL REGISTRATION:
      NCT01095770. URL: https://clinicaltrials.gov/ct2/show/NCT01095770.

PMID- 26310301
TI  - Paenibacillus insulae sp. nov., isolated from soil.
AB  - A Gram-stain-positive, motile, endospore-forming, and strictly aerobic rod-shaped
      bacterium designated DS80(T) was isolated from an island soil. The strain DS80(T)
      grew at temperatures between 15 and 40 degrees C (optimum = 30 degrees C) and at
      pH values ranging from 5.0 to 9.0 (optimum = 7.0). The phylogenetic analysis
      based on the comparisons of the 16S rRNA gene sequences showed that the isolate
      was affiliated to the genus Paenibacillus and was mostly related to Paenibacillus
      assamensis GPTSA11(T) (with the sequence similarity of 96.33%) and Paenibacillus
      urinalis 5402403(T)(95.48%). The G+C content of the genomic DNA was 44.0 mol% and
      the major fatty acids were anteiso-C15:0, iso-C15:0, iso-C16:0, and C16:1
      omega11c. Strain DS80(T) contained MK-7 as the major menaquinone, and
      phosphatidylglycerol, phosphatidylethanolamine, and diphosphatidylglycerol as the
      major polar lipids. The peptidoglycan contained a major amount of meso
      diaminopimelic acid. The chemotaxonomic profile of strain DS80(T) was consistent
      with that of Paenibacillus. However, the phenotypic properties clearly separated
      the strain from other species of the genus. Accordingly, a new species,
      Paenibacillus insulae sp. nov., is proposed (type strain =DS80(T) =JCM 17278(T)
      =KCTC 13833(T)). 

PMID- 26310302
TI  - Chujaibacter soli gen. nov., sp. nov., isolated from soil.
AB  - A Gram-staining-negative, aerobic, non-flagellated, rod-shaped bacterial strain,
      KIS55-21(T), was isolated from a soil sample from Chuja Island, Jeju Province,
      Republic of Korea. Strain KIS55-21(T) grew optimally at pH 7.0, at 28-30 degrees
      C and in the presence of 0% (w/v) NaCl. Neighbor-joining and maximum-likelihood
      trees based on the 16S rRNA gene sequences revealed that strain KIS55-21(T) fell
      within the family Xanthomonadaceae and was closely related to Metallibacterium
      scheffleri DKE(T). Strain KIS55-21(T) exhibited the highest 16S rRNA gene
      sequence similarity (92.6%) to that of M. scheffleri DKE(T), with similarities of
      less than 92.0% to those of the genera Dokdonella, Rhodanobacter, Aquimonas, and
      Frateuria. Strain KIS55-21(T) contained ubiquinone-8 (Q-8) as the predominant
      ubiquinone, iso-C17:0, summed feature 9 (iso-C17:1 omega9c and/or C16:0 10
      methyl), anteiso-C17:0 and C16:0 as the major fatty acids, and
      phosphatidylethanolamine, aminophospholipid, phosphatidylglycerol,
      diphosphatidylglycerol, and phosphatidylmonomethylethanolamine as the main polar
      lipids. The DNA G+C content of strain KIS55-21(T) was 65.9 mol%. Differential
      phenotypic and chemotaxonomic properties and phylogenetic data of strain KIS55
      21(T) demonstrated that this strain is distinguishable from closely related
      genera within the family Xanthomonadaceae. On the basis of the data presented,
      strain KIS55-21(T) is considered to represent a novel genus and species, for
      which the name Chujaibacter soli gen. nov., sp. nov. is proposed. The type strain
      is KIS55-21(T) (=KACC 16971(T) =DSM 28578(T)). 

PMID- 26310303
TI  - Characterization of bacterial diversity associated with deep sea ferromanganese
      nodules from the South China Sea.
AB  - Deep sea ferromanganese (FeMn) nodules contain metallic mineral resources and
      have great economic potential. In this study, a combination of culture-dependent
      and culture-independent (16S rRNA genes clone library and pyrosequencing) methods
      was used to investigate the bacterial diversity in FeMn nodules from Jiaolong
      Seamount, the South China Sea. Eleven bacterial strains including some moderate
      thermophiles were isolated. The majority of strains belonged to the phylum
      Proteobacteria; one isolate belonged to the phylum Firmicutes. A total of 259
      near full-length bacterial 16S rRNA gene sequences in a clone library and 67,079
      valid reads obtained using pyrosequencing indicated that members of the
      Gammaproteobacteria dominated, with the most abundant bacterial genera being
      Pseudomonas and Alteromonas. Sequence analysis indicated the presence of many
      organisms whose closest relatives are known manganese oxidizers, iron reducers,
      hydrogen-oxidizing bacteria and methylotrophs. This is the first reported
      investigation of bacterial diversity associated with deep sea FeMn nodules from
      the South China Sea. 

PMID- 26310304
TI  - Identification of Psk2, Skp1, and Tub4 as trans-acting factors for uORF
      containing ROK1 mRNA in Saccharomyces cerevisiae.
AB  - Rok1, a DEAD-box RNA helicase, is involved in rRNA processing and the control of
      cell cycle progression in Saccharomyces cerevisiae. Rok1 protein expression is
      cell cycle-regulated, declining at G1/S and increasing at G2. The downregulation
      of Rok1 expression in G1/S phase is mediated by the inhibitory action of two
      upstream open reading frames (uORFs) in the ROK1 5'-untranslated region (5'UTR).
      We identified Psk2 (PAS kinase), Skp1 (kinetochore protein) and Tub4 (gamma
      tubulin protein) as ROK1 5'UTR-interacting proteins using yeast three-hybrid
      system. A deletion analysis of PSK2 or inactivation of temperature-sensitive
      alleles of SKP1 and TUB4 revealed that Rok1 protein synthesis is repressed by
      Psk2 and Skp1. This repression appeared to be mediated through the ROK1 uORF1. In
      contrast, Tub4 plays a positive role in regulating Rok1 protein synthesis and
      likely after the uORF1-mediated inhibitory regulation. These results suggest that
      5'UTR-interacting proteins, identified using three hybrid screening, are
      important for uORF-mediated regulation of Rok1 protein expression. 

PMID- 26310305
TI  - Roles of RpoS in Yersinia pseudotuberculosis stress survival, motility, biofilm
      formation and type VI secretion system expression.
AB  - RpoS (sigma(S)), the stationary phase/stress sigma factor, controls the
      expression of a large number of genes involved in cellular responses to a variety
      of stresses. However, the role of RpoS appears to differ in different bacteria.
      While RpoS is an important regulator of flagellum biosynthesis, it is associated
      with biofilm development in Edwardsiella tarda. Biofilms are dense communities
      formed by bacteria and are important for microbe survival under unfavorable
      conditions. The type VI secretion system (T6SS) discovered recently is reportedly
      associated with several phenotypes, ranging from biofilm formation to stress
      sensing. For example, Vibrio anguillarum T6SS was proposed to serve as a sensor
      for extracytoplasmic signals and modulates RpoS expression and stress response.
      In this study, we investigated the physiological roles of RpoS in Yersinia
      pseudotuberculosis, including bacterial survival under stress conditions,
      flagella formation, biofilm development and T6SS expression. We found that RpoS
      is important in resistance to multiple stressors-including H2O2, acid, osmotic
      and heat shock-in Y. pseudotuberculosis. In addition, our study showed that RpoS
      not only modulates the expression of T6SS but also regulates flagellum formation
      by positively controlling the flagellar master regulatory gene flhDC, and affects
      the formation of biofilm on Caenorhabditis elegans by regulating the synthesis of
      exopolysaccharides. Taken together, these results show that RpoS plays a central
      role in cell fitness under several adverse conditions in Y. pseudotuberculosis. 

PMID- 26310306
TI  - The effect of dietary bovine colostrum on respiratory syncytial virus infection
      and immune responses following the infection in the mouse.
AB  - Human respiratory syncytial virus (hRSV) is the most common cause of respiratory
      tract infection among young children because of immature T cell immunity of them
      against hRSV. CD8 T cells play a pivotal role in clearing hRSV and preventing
      subsequent infection. We examined the effects of dietary bovine colostrum on
      virus infection and CD8 T cell responses following hRSV infection in the mouse
      model. Mice received bovine colostrum for 14 days prior to hRSV challenge, and
      lung indexes (severity of symptom) and lung virus titers were analyzed. In
      addition, the activation of CD8 T cells in the bronchoalveolar lavage fluids
      (BALFs) of mice receiving bovine colostrum were compared with those in the BALFs
      of mice receiving phosphate-buffered saline (PBS) or ribavirin, post virus
      challenge. The severity of infection and lung virus titers were reduced in the
      mice receiving bovine colostrum, compared to those receiving PBS. Moreover CD8 T
      cell responses were selectively enhanced in the former. Our results suggest that
      dietary bovine colostrum exerts the effects to inhibit hRSV and ameliorate the
      symptom by hRSV infection, and enhances the CD8 T cell response during the hRSV
      infection. 

PMID- 26310307
TI  - Association Between Local Pediatric Vaccination Rates and Patterns of
      Pneumococcal Disease in Adults.
AB  - BACKGROUND: Pneumococcal conjugate vaccine (PCV) is now recommended for use in
      adults in the United States. Because vaccination of children with PCVs protects
      adults from the targeted serotypes, local variations in PCV uptake among children
      could influence disease patterns in adults. METHODS: We obtained ZIP code-level
      data on invasive pneumococcal disease (IPD) from an active population-based
      surveillance system in Connecticut (study interval, 1998-2009) and ZIP code-level
      data on immunization with at least 3 or at least 4 doses of 7-valent PCV (PCV7)
      from the state immunization registry. We fit logistic regression models to
      estimate the proportion of IPD cases among adults aged >40 years that were caused
      by PCV7-targeted serotypes. Covariates included ZIP code-level socioeconomic
      indicators (eg, percentage of the population that was black and income per
      capita), the percentage of the population that received 3 or 4 doses of PCV7
      (mean centered), and a linear spline to control for the average rate of decline
      across all ZIP codes. RESULTS: ZIP codes that had a higher proportion of children
      that did not complete the 4-dose PCV7 series had a higher proportion of adult IPD
      cases caused by PCV7 serotypes. CONCLUSIONS: Local variations in PCV uptake (and
      receipt of the booster dose) might influence the effectiveness of PCVs in
      preventing pneumococcal disease in adults.

PMID- 26310308
TI  - Persistent HIV Type 1 Seronegative Status Is Associated With Lower CD8+ T-Cell
      Activation.
AB  - We leveraged data from the Preexposure Prophylaxis Initiative (iPrEx), a global
      trial of preexposure chemoprophylaxis against human immunodeficiency virus type 1
      (HIV-1) infection, to compare T-cell activation between those who remained
      negative for HIV-1 and those who became infected during the trial. The frequency
      of CD38(+)HLA-DR(+) CD8(+) T cells was greater in those who seroconverted,
      relative to the frequency in those who remained uninfected (1.30% vs 0.82%,
      respectively; P = .005). This translated to an odds ratio of 4.26 (95% confidence
      interval, 1.54-11.78) for the association between CD8(+) T-cell activation and
      infection with HIV-1. T-cell activation may be a biomarker for elevated HIV-1
      infection risk. 

PMID- 26310309
TI  - Programmatic Implications of Acute and Early HIV Infection.
AB  - Human immunodeficiency virus (HIV) infection includes acute, early, chronic, and
      late stages. Acute HIV infection lasts approximately 3 weeks and early HIV
      infection, which includes acute HIV infection, lasts approximately 7 weeks. Many
      testing and blood screening algorithms detect HIV antibodies about 3 weeks after
      HIV infection. Incidence estimates are based on results of modeling, cohort
      studies, surveillance, and/or assays. Viral load is the key modifiable risk
      factor for HIV transmission and peaks during acute and early HIV infection.
      Empirical evidence characterizing the impact of acute and early HIV infection on
      the spread of the HIV epidemic are limited. Time trends of HIV prevalence
      collected from concentrated and generalized epidemics suggest that acute and
      early HIV infection may have a limited role in population HIV transmission.
      Collectively, these data suggest that acute and early HIV infection is relatively
      short and does not currently require fundamentally different programmatic
      approaches to manage the HIV/AIDS epidemic in most settings. Research and
      surveillance will inform which epidemic contexts and phases may require tailored
      strategies for these stages of HIV infection. 

PMID- 26310310
TI  - Kinin B1 Receptor Inhibition With BI113823 Reduces Inflammatory Response,
      Mitigates Organ Injury, and Improves Survival Among Rats With Severe Sepsis.
AB  - BACKGROUND: This study examined the therapeutic effects of an orally active
      nonpeptide kinin B1 receptor antagonist, BI113823, in a clinically relevant
      experimental model of polymicrobial sepsis in rats. METHODS: Sepsis was induced
      by cecal ligation and puncture (CLP). Animals received treatment with either
      vehicle or BI113823. The experiment was terminated in the first set of animals 15
      hours after CLP. Seven-day survival following CLP was determined in the second
      set of animals. RESULTS: Compared with vehicle treatment, administration of
      BI113823 reduced neutrophil and macrophage infiltration, reduced cytokine
      production, attenuated intestinal mucosal hyperpermeability, prevented
      hemodynamic derangement, and improved cardiac output. Furthermore, administration
      of BI113823 reduced inducible nitric oxide synthase expression and the injury
      score in the lung and attenuated nuclear factor KB activation and apoptosis in
      the liver. Treatment with BI113823 also reduced plasma levels of cardiac
      troponin, aspartate aminotransferase, alanine aminotransferase, urea, and
      lactate, as well as proteinuria. Finally, administration of BI113823 improved the
      7-day survival rate following CLP in rats. CONCLUSIONS: Administration of
      BI113823 reduced systemic and tissue inflammatory responses, prevented
      hemodynamic derangement, attenuated multiorgan injury, and improved overall
      survival.

PMID- 26310311
TI  - A systematic review of the influence of rice characteristics and processing
      methods on postprandial glycaemic and insulinaemic responses.
AB  - Rice is an important staple food for more than half of the world's population.
      Especially in Asian countries, rice is a major contributor to dietary glycaemic
      load (GL). Sustained consumption of higher-GL diets has been implicated in the
      development of chronic diseases such as type 2 diabetes mellitus. Given that a
      reduction in postprandial glycaemic and insulinaemic responses is generally seen
      as a beneficial dietary change, it is useful to determine the variation in the
      range of postprandial glucose (PPG) and insulin (PPI) responses to rice and the
      primary intrinsic and processing factors known to affect such responses.
      Therefore, we identified relevant original research articles on glycaemic
      response to rice through a systematic search of the literature in Scopus, Medline
      and SciFinder databases up to July 2014. Based on a glucose reference value of
      100, the observed glycaemic index values for rice varieties ranged from 48 to 93,
      while the insulinaemic index ranged from 39 to 95. There are three main factors
      that appear to explain most of the variation in glycaemic and insulinaemic
      responses to rice: (1) inherent starch characteristics (amylose:amylopectin ratio
      and rice cultivar); (2) post-harvest processing (particularly parboiling); (3)
      consumer processing (cooking, storage and reheating). The milling process shows a
      clear effect when compared at identical cooking times, with brown rice always
      producing a lower PPG and PPI response than white rice. However, at longer
      cooking times normally used for the preparation of brown rice, smaller and
      inconsistent differences are observed between brown and white rice. 

PMID- 26310312
TI  - Bridging the gap between in vitro and in vivo: Dose and schedule predictions for
      the ATR inhibitor AZD6738.
AB  - Understanding the therapeutic effect of drug dose and scheduling is critical to
      inform the design and implementation of clinical trials. The increasing
      complexity of both mono, and particularly combination therapies presents a
      substantial challenge in the clinical stages of drug development for oncology.
      Using a systems pharmacology approach, we have extended an existing PK-PD model
      of tumor growth with a mechanistic model of the cell cycle, enabling simulation
      of mono and combination treatment with the ATR inhibitor AZD6738 and ionizing
      radiation. Using AZD6738, we have developed multi-parametric cell based assays
      measuring DNA damage and cell cycle transition, providing quantitative data
      suitable for model calibration. Our in vitro calibrated cell cycle model is
      predictive of tumor growth observed in in vivo mouse xenograft studies. The model
      is being used for phase I clinical trial designs for AZD6738, with the aim of
      improving patient care through quantitative dose and scheduling prediction. 

PMID- 26310314
TI  - Optimizing parental involvement in caring for preterm infants.

PMID- 26310313
TI  - Susceptibility loci in lung cancer and COPD: association of IREB2 and FAM13A with
      pulmonary diseases.
AB  - Genome-wide association studies have identified loci at 15q25 (IREB2) and 4q22
      (FAM13A), associated with lung cancer (LC) and chronic obstructive pulmonary
      disease (COPD). The aim of our research was to determine the association of IREB2
      and FAM13A SNPs with LC and severe/very severe COPD patients. We examined IREB2
      variants (rs2568494, rs2656069, rs10851906, rs13180) and FAM13A (rs1903003,
      rs7671167, rs2869967) among 1.141 participants (468 LC, 149 COPD, 524 smoking
      controls). The frequency of the minor IREB2 rs2568494 AA genotype, was higher in
      LC vs controls (P = 0.0081, OR = 1.682). The FAM13A rs2869967 was associated with
      COPD (minor CC genotype: P = 0.0007, OR = 2.414). The rs1903003, rs7671167 FAM13A
      variants confer a protective effect on COPD (both P < 0.002, OR < 0.405).
      Haplotype-based tests identified an association of the IREB2 AAAT haplotype with
      LC (P = 0.0021, OR = 1.513) and FAM13A TTC with COPD (P = 0.0013, OR = 1.822).
      Cumulative genetic risk score analyses (CGRS), derived by adding risk alleles,
      revealed that the risk for COPD increased with the growing number of the FAM13A
      risk alleles. OR (95% CI) for carriers of >=5 risk alleles reached 2.998 (1.8 to
      4.97) compared to the controls. This study confirms that the IREB2 variants
      contribute to an increased risk of LC, whereas FAM13A predisposes to increased
      susceptibility to COPD. 

PMID- 26310315
TI  - Unplanned extubation in NICU patients: are we speaking the same language?

PMID- 26310317
TI  - Transcutaneous bilirubin levels in newborns <35 weeks' gestation.

PMID- 26310316
TI  - Medical and ethical challenges in the case of a prenatally undiagnosed massive
      congenital brain tumor.
AB  - Fetal and neonatal brain tumors are rare. Prenatal ultrasound aids early tumor
      detection. Nonetheless, we encountered a preterm neonate born at 32 weeks
      gestation with a massive supratentorial glioma, which was undetected on
      ultrasound at 19-6/7 weeks gestation. The patient presented at birth with
      unanticipated massive macrocephaly. Resuscitation and stabilization were
      difficult, but the medical team felt that futility of care was not established
      and opted to transfer the baby to an academic center for further imaging and
      specialist consultations. Diagnosis of an extensive, inoperable tumor was
      confirmed and support withdrawn. Postmortem histologic examination and
      immunohistochemical stains identified the majority of tumor cells as glial in
      origin. This case report illustrates well how a severe and potentially fatal
      anomaly, which remained undetected prenatally, presented the medical team and
      family with multiple medical, ethical and emotional challenges at birth;
      decisions regarding futility of care in the neonatal transport setting are
      difficult. 

PMID- 26310318
TI  - A combined pre-clinical meta-analysis and randomized confirmatory trial approach
      to improve data validity for therapeutic target validation.
AB  - Biomedical research suffers from a dramatically poor translational success. For
      example, in ischemic stroke, a condition with a high medical need, over a
      thousand experimental drug targets were unsuccessful. Here, we adopt methods from
      clinical research for a late-stage pre-clinical meta-analysis (MA) and randomized
      confirmatory trial (pRCT) approach. A profound body of literature suggests NOX2
      to be a major therapeutic target in stroke. Systematic review and MA of all
      available NOX2(-/y) studies revealed a positive publication bias and lack of
      statistical power to detect a relevant reduction in infarct size. A fully powered
      multi-center pRCT rejects NOX2 as a target to improve neurofunctional outcomes or
      achieve a translationally relevant infarct size reduction. Thus stringent
      statistical thresholds, reporting negative data and a MA-pRCT approach can ensure
      biomedical data validity and overcome risks of bias. 

PMID- 26310320
TI  - Ionic Transport through Chemically Functionalized Hydrogen Peroxide-Sensitive
      Asymmetric Nanopores.
AB  - We describe the fabrication of a chemical-sensitive nanofluidic device based on
      asymmetric nanopores whose transport characteristics can be modulated upon
      exposure to hydrogen peroxide (H2O2). We show experimentally and theoretically
      that the current-voltage curves provide a suitable method to monitor the H2O2
      mediated change in pore surface characteristics from the electronic readouts. We
      demonstrate also that the single pore characteristics can be scaled to the case
      of a multipore membrane whose electric outputs can be readily controlled. Because
      H2O2 is an agent significant for medical diagnostics, the results should be
      useful for sensing nanofluidic devices. 

PMID- 26310319
TI  - Effect of Berberine on promoting the excretion of cholesterol in high-fat diet
      induced hyperlipidemic hamsters.
AB  - BACKGROUND: Berberine (BBR), as a new medicine for hyperlipidemia, can reduce the
      blood lipids in patients. Mechanistic studies have shown that BBR activates the
      extracellular-signal regulated kinase pathway by stabilizing low-density
      lipoprotein receptor mRNA. However, aside from inhibiting the intestinal
      absorption of cholesterol, the effects of BBR on other metabolic pathways of
      cholesterol have not been reported. This study aimed to investigate the action of
      BBR on the excretion of cholesterol in high-fat diet-induced hyperlipidemic
      hamsters. METHODS: Golden hamsters were fed a high-fat diet (HFD) for 6 weeks to
      induce hyperlipidemia, followed by oral treatment with 50 and 100 mg/kg/day of
      BBR or 10 and 30 mg/kg/day of lovastatin for 10 days, respectively. The levels of
      total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol
      (LDL-C), transaminases, and total bile acid in the serum, liver, bile and feces
      were measured using an enzyme-linked immunosorbent assay. The cholesterol (as
      well as coprostanol) levels in the liver, bile and feces were determined by gas
      chromatography-mass spectrometry. RESULTS: The HFD hamsters showed significantly
      hyperlipidemic characteristics compared with the normal hamsters. Treatment with
      BBR for 10 days reduced the serum TC, TG and LDL-C levels in HFD hamsters by 44
      70, 34-51 and 47-71%, respectively, and this effect was both dose- and time
      dependent. Initially, a large amount of cholesterol accumulated in the
      hyperlipidemic hamster livers. After BBR treatment, reductions in the liver
      cholesterol were observed by day 3 and became significant by day 7 at both doses
      (P < 0.001). Meanwhile, bile cholesterol was elevated by day 3 and significantly
      increased at day 10 (P < 0.001). BBR promoted cholesterol excretion from the
      liver into the bile in hyperlipidemic hamsters but not in normal hamsters, and
      these results provide a link between the cholesterol-lowering effect of BBR with
      cholesterol excretion into the bile. CONCLUSIONS: We conclude that BBR
      significantly promoted the excretion of cholesterol from the liver to the bile in
      hyperlipidemic hamsters, which led to large decreases in the serum TC, TG and LDL
      C levels. Additionally, compared with lovastatin, the BBR treatment produced no
      obvious side effects on the liver function.

PMID- 26310321
TI  - The efficacy and acceptability of psychological interventions for depression:
      where we are now and where we are going.
AB  - Depression is an eminently treatable disorder, although estimates of treatment
      efficacy have been inflated by publication bias. Patients with less severe
      depressions respond to even nonspecific interventions, whereas patients with more
      severe depressions require treatments that mobilize specific mechanisms. The
      cognitive and behavior therapies can be as efficacious as medications in the
      treatment of severe depression and have an enduring effect that medications lack.
      Medications may interfere with those enduring effects when added in combination
      and may prolong the life of the underlying episode when used alone. Thus the
      cognitive behavioral interventions might be the optimal first-line treatments for
      depression. 

PMID- 26310322
TI  - Critically appraised topic on adverse food reactions of companion animals (1):
      duration of elimination diets.
AB  - BACKGROUND: Restrictive (i.e. elimination)-provocation dietary trials remain the
      standard of care to diagnose cutaneous adverse food reactions (CAFRs) in dogs and
      cats. There is currently no consensus on the duration of elimination diet trials
      that would permit the highest sensitivity of diagnosis of CAFR in companion
      animals. RESULTS: The search for, and review and analysis of the best evidence
      available as of December 14, 2014 suggests that, by 5 weeks in dogs and 6 weeks
      in cats after starting an elimination diet, more than 80 % of patients had
      achieved a remission of clinical signs of CAFR. Increasing the diet trial
      duration to 8 weeks leads to a complete remission in more than 90 % of dogs and
      cats with CAFR. CONCLUSIONS: For diagnosing CAFRs in more than 90 % of dogs and
      cats, elimination diet trials should last at least 8 weeks.

PMID- 26310323
TI  - Magnetic resonance imaging anatomy of the rabbit brain at 3 T.
AB  - BACKGROUND: Rabbits are widely accepted as an animal model in neuroscience
      research. They also represent very popular pet animals, and, in selected clinical
      cases with neurological signs, magnetic resonance imaging (MRI) may be indicated
      for imaging the rabbit brain. Literature on the normal MRI anatomy of the rabbit
      brain and associated structures as well as related reference values is sparse.
      Therefore, it was the purpose of this study to generate an MRI atlas of the
      normal rabbit brain including the pituitary gland, the cranial nerves and major
      vessels by the use of a 3 T magnet. RESULTS: Based on transverse, dorsal and
      sagittal T2-weighted (T2w) and pre- and post-contrast 3D T1-weighted (T1w)
      sequences, 60 intracranial structures were identified and labeled. Typical
      features of a lissencephalic brain type were described. In the 5 investigated
      rabbits, on T1w images a crescent-shaped hyperintense area caudodorsally in the
      pituitary gland most likely corresponded to a part of the neurohypophysis. The
      optic, trigeminal, and in part, the facial, vestibulocochlear and trochlear
      nerves were identified. Mild contrast enhancement of the trigeminal nerve was
      present in all rabbits. Absolute and relative size of the pituitary gland,
      midline area of the cranial and caudal cranial fossa and height of the tel- and
      diencephalon, 3rd and 4th ventricles were also determined. CONCLUSIONS: These
      data established normal MRI appearance and measurements of the rabbit brain.
      Results provide reference for research studies in rabbits and, in rare instances,
      clinical cases in veterinary medicine.

PMID- 26310324
TI  - [Tenolysis of the flexor tendons in the hand].
AB  - BACKGROUND: Properly gliding flexor tendons is mandatory for the normal
      functioning of the finger and thumb. Any damage to tendons, tendon sheath or
      adjacent tissue can lead to the formation of adhesions that inhibit the normal
      gliding function. If adhesions limit the digital function and adequate hand
      therapy does not provide further progress, then surgical intervention should be
      considered. AIM: The authors' strategy and treatment algorithm for flexor
      tenolysis are presented in the context of the current literature. METHODS: There
      is no absolute indication for flexor tenolysis. The decision should be made in a
      motivated patient who has access to adequate postoperative hand therapy. It
      should be based on healed fractures and osteotomies, mature soft tissue coverage,
      intact tendons and gliding tissues, and a full range of passive flexion, and
      preferably extension of the affected joints. The principle of flexor tenolysis is
      the consequent resection of all adhesive tissue around the tendon inside and
      outside the tendon sheath, with preservation of as many pulley sections as
      possible. Therefore, extensive approaches are frequently necessary. Arthrolysis
      and the resolution of unfavorable scars, the resection of scarred lumbricals, and
      pulley reconstruction are additional procedures that are frequently performed.
      RESULTS: In the literature, improvement in the range of motion is between 59 and
      84 %. Good and excellent functional results are reported in 60-80 % of the cases.
      Nevertheless, in selected cases, functional deterioration occurs. Flexor tendon
      ruptures after tenolysis were observed in 0-8 % of the patients. DISCUSSION: With
      regard to complications such as secondary tendon ruptures, loss of pulleys, and
      scar formation, flexor tenolysis is part of a reconstructive ladder that includes
      further procedures. In the case of failure or complications, salvage procedures
      such as arthrodesis, amputation, and ray resection or staged flexor tendon
      reconstruction including tendon grafting are recommended. After successful flexor
      tenolysis long-term hand therapy for at least 3-6 months is mandatory to maintain
      the intraoperative gain of function.

PMID- 26310326
TI  - [Health economic evaluation of AIDS response].
AB  - During the past over 20 years of AIDS response in China, different fields from
      the international society and domestic sources provide significant amounts of
      resources for China's AIDS response. The investment, distribution and use of
      these resources and their effect has become the concern of the society. The
      health economic evaluation method is used to scientifically answer these
      questions, which is also the motivation of the evaluation studies. Based on
      several studies on health economic evaluation of AIDS response in this issue,
      concepts and issues related to this area are summarized. It is important for the
      readers to make a point of health economics evaluation, and it is also of great
      importance to know its limitations to provide the basis for future proper use of
      AIDS health economic evaluation results. 

PMID- 26310325
TI  - The transcription factor ERG increases expression of neurotransmitter receptors
      on prostate cancer cells.
AB  - BACKGROUND: The TMPRSS2-ERG gene fusion occurs in about half of prostate cancer
      (PCa) cases and results in overexpression of the transcription factor ERG.
      Overexpression of ERG has many effects on cellular function. However, how these
      changes enhance cell growth and promote tumor development is unclear. METHODS: To
      investigate the role of ERG, LNCaP and PC3 cells were transfected with ERG and
      gene expression and metabolic profile were analyzed. RESULTS: Our data show that
      expression of ERG induces overexpression of many nicotinicacetylcholine receptors
      (nAChRs). In addition, metabolic profiling by LC-MS/MS revealed elevated
      production of several neurotransmitters in cells expressing ERG. Consistently,
      treatment of ERG-expressing cells with nicotine induced elevated calcium influx,
      GSK3beta (Ser9) phosphorylation and cell proliferation. Finally, we show that PCa
      patientswho are smokers have larger tumors if their tumors are TMPRSS2-ERG gene
      fusion positive. CONCLUSION: Collectively, our data suggest that ERG sensitizes
      prostate tumor cells to neurotransmitter receptor agonists like nicotine.

PMID- 26310327
TI  - [Perfluoroalkyl substances: emerging environmental contaminants involving
      potential health risk].
AB  - Perfluoroalkyl substances (PFASs) have been distributed in environment and human
      body worldwide. Due to their bioaccumulative and multiple organ toxic, these
      compounds have raised more and more attention in recent years. The precursors of
      PFASs can be metabolized to PFASs both in environment and human body, which makes
      an important contribution to human body burdens. Apart from transformation into
      PFASs, some of these precursors themselves or their metabolic intermediates also
      have toxicity effects, such as estrogen-like properties, protein binding,
      cytotoxicity and so on, and there might be a potential harmful impact on human
      health. In this paper, the toxicity and biotransformation of PFASs and their
      precursors were introduced briefly. 

PMID- 26310328
TI  - [Comparing the safety of vaccination on vastus lateralis muscle and deltoid
      muscle of infants with haemophilus influenzae type b conjugate vaccine].
AB  - OBJECTIVE: To compare the safety of haemophilus influenzae type b (Hib) vaccine
      vaccination on vastus lateralis muscle and deltoid muscle of infant. METHODS: A
      total of 408 3-4 months old infants were divided into vastus lateralis muscle
      group and deltoid muscle group in Beijing, 2014. They were divided into the
      vastus lateralis muscle group (204) and deltoid muscle group (204) by extracting
      random number. Each observation object was given 3 doses of Hib vaccine according
      to the program. Collected systemic and local reactions after vaccination and
      calculated the incidence of adverse reactions. RESULTS: A total of 61 infants
      were quitted during the study, 1 132 doses were observed. The total reactions
      incidence of Vastus lateralis muscle group and Deltoid muscle group were 33.0%
      (186/564) and 27.6% (157/568) with no statistical differences (chi2 = 3.818, P =
      0.059). The two groups incidence at the same day of vaccination (day 0) which the
      highest were 23.2% (131/564) and 20.6% (117/568), then declined with time (linear
      trend test vastus lateralis muscle group chi2 = 36.600, P < 0.001,deltoid muscle
      group chi2 = 29.947, P < 0.001), day 1 were 20.4% (115/564) and 17.6% (100/568),
      day 2 were 16.0% (90/564) and 13.4% (76/568), day 3 were 10.3% (58/564) and 10.6%
      (60/568), day 4-7 were 11.2% (63/564) and 11.3% (64/568). No serious adverse
      events (SAE) were reported during the study. The local reactions incidence of two
      groups were 7.1% (40/564) and 7.7% (44/568)with no statistical differences (chi2
      = 0.176, P = 0.675). The systemic reactions incidence of two groups were 25.9%
      (146/564) and 20.6% (117/568) with obvious statistical differences (chi2 = 4.437,
      P = 0.035). The fever incidence of vastus lateralis muscle group (11.5% (65/564))
      was higher than Deltoid muscle group (4.4% (25/568)) with obvious statistical
      differences (chi2 = 4.868, P = 0.027). The 1st dose incidence of fever and
      abnormal crying of vastus lateralis muscle group (fever 11.3% (23/204), abnormal
      crying 19.1% (39/204)) was higher than deltoid muscle group (fever 4.4% (9/204),
      abnormal crying 11.8% (24/204)) and the 2nd dose of diarrhea of deltoid muscle
      group (11.6% (22/190)) was higher than vastus lateralis muscle group (5.9%
      (11/187)) with obvious statistical differences (fever chi2 = 15.288, P < 0.001,
      abnormal crying chi2 = 4.224, P = 0.040, diarrhea chi2 = 3.829, P = 0.046).
      CONCLUSION: Both vastus lateralis muscle group and deltoid muscle group had lower
      incidence of adverse reactions after vaccination. No serious adverse events were
      associated with vaccination. Vastus lateralis muscle vaccination as well as
      deltoid muscle vaccination demonstrated safe.

PMID- 26310329
TI  - [Evaluation of safety of haemophilus influenza type b(Hib) conjugate vaccine in
      postmarketing based on the immunization information management system].
AB  - OBJECTIVE: To analyze the occurrence feature of adverse events following
      immunization (AEFI) of Hib conjugate vaccine (HibCV) and to evaluate the safety
      of HibCV in postmarketing. METHODS: 2008-2013 HibCV AEFI data were collected
      through national AEFI information management system, which were downloaded in
      March 18, 2014.The demographic information and inoculation quantity of HibCV were
      from Immunization information management system in Jiangsu province. The
      incidence rate and 95% CI value of AEFI, common vaccine reaction and rare vaccine
      reaction following immunization of HibCV were calculated. The differences in the
      incidence rate of common vaccine reaction and rare vaccine reaction among sex,
      months of age, and number of injections were compared by means of (chi2 tests.
      RESULTS: A total of 6.16 million doses of vaccine were administered in Jiangsu
      province during 2008-2013, and 4 718 vaccinees reported having adverse event, for
      a rate of 76.60/100 000 (95% CI: 74.42/100 000-78.79/100 000). The incidence rate
      of common vaccine reaction and rare vaccine reaction was 71.10/100 000 (95% CI:
      68.99/100 000-73.20/100 000) and 5.16/100 000 (95% CI: 4.60/100 000-5.73/100
      000), respectively. The main symptoms of common vaccine reactions were fever,
      swelling, indurations and gastrointestinal reactions. The incidence rates of them
      were 40.54/100 000, 35.09/100 000, 12.94/100 000 and 0.36/100 000 in turn. The
      main symptoms of rare vaccine reactions were anaphylactic rashes and angioedema,
      the incidence rates of which were 4.77/100 000 and 0.15/100 000 respectively.
      91.39% (4 002/4 379) of common vaccine reactions and 88.36% (281/318) of rare
      vaccine reactions happened within 1 d after vaccination. Anaphylactic shock (3
      cases) and laryngeal edema (1 case) all happened within 1 d after vaccination.
      The incidence rate of common vaccine reactions among boys (79.72/100 000, 2 641/3
      313 071) was higher than that of girls (61.07/100 000, 1 738/2 846 001) (chi2 =
      74.92, P < 0.001). The incidence rate of common vaccine reactions among children
      aged >= 12 month-old (86.82/100 000, 2 200/2 533 949) was higher than that among
      children aged 2-11 month-old (60.11/100 000, 2 179/3 625 123) (chi2 = 149.79, P <
      0.001). The incidence rate of common vaccine reactions in children vaccinated the
      first dose (78.93/100 000, 2 666/3 377 614) was higher than that in children
      vaccinated the second or third or fourth dose (61.59/100 000, 1 713/2 781 458)
      (chi2 = 64.59, P < 0.001). The incidence rate of rare vaccine reactions in
      children vaccinated the first dose (6.69/100 000, 226/3 377 614) was higher than
      that in children vaccinated the second or third or fourth dose (3.31/100 000,
      92/2 781 458) (chi2 = 33.82, P < 0.001). CONCLUSION: The safety of HibCV among
      children was relative good. However, the surveillance should still focus on the
      anaphylactoid reactions of anaphylactic shock and laryngeal edema after HibCV
      immunization.

PMID- 26310330
TI  - [Susceptibility of human influenza A (H3N2) viruses to neuraminidase inhibitors
      isolated during 2011-2012 in China].
AB  - OBJECTIVE: To analyze the susceptibility of influenza A (H3N2) viruses to
      neuraminidase inhibitors during 2011-2012 in Mainland China. METHODS: All the
      tested viruses were obtained from the Chinese National Influenza Surveillance
      Network, which covers 31 provinces in mainland China, including 408 network
      laboratories and 554 sentinel hospitals. In total 1 903 viruses were selected
      with isolation date from January 1, 2011 to December 31, 2012 in Mainland China,
      among these viruses, 721 were confirmed to be influenza A (H3N2) virus by Chinese
      National Influenza Center and tested for the susceptibility to oseltamivir and
      zanamivir using chemiluminescence-based assay. The neuraminidase inhibitor
      sensitive reference virus A/Washington/01/2007 (119E) and oseltamivir resistant
      virus A/Texas/12/2007 (E119V) were used as control in this study. The t -test was
      used to compare the difference of NAI susceptibility of viruses isolated from
      different years. RESULTS: The half maximal inhibitory concentration (IC50) of
      A/Washington/01/2007 for oseltamivir and zanamivir was (0.10 +/- 0.02) and (0.30
      +/- 0.05) nmol/L, respectively. The IC50 of A/Texas/12/2007 for oseltamivir and
      zanamivir was (4.27 +/- 1.60) and (0.20 +/- 0.03) nmol/L, respectively. Among the
      721 influenza A (H3N2) viruses, 132 influenza A (H3N2) viruses were isolated in
      2011 and 589 influenza A (H3N2) viruses were isolated in 2012. The IC50 for
      oseltamivir ranged from 0.04 to 0.62 nmol/L for viruses isolated in 2011 and
      ranged from 0.02 to 0.95 nmol/L for viruses in 2012, and the IC50 of all the
      viruses tested was within 10-fold IC50 (1.0 nmol/L) of the neuraminidase
      inhibitor sensitive reference virus A/Washington/01/2007. The IC50 of zanamivir
      ranged from 0.12 to 0.80 nmol/L for viruses in 2011 and ranged from 0.04 to 0.72
      nmol/L for viruses in 2012, and was within 10-fold IC50 (3.0 nmol/L) of the
      neuraminidase inhibitor sensitive reference virus A/Washington/01/2007.
      CONCLUSION: The influenza A(H3N2) viruses isolated during 2011-2012 in Mainland
      China were tested to be sensitive to oseltamivir and zanamivir.

PMID- 26310331
TI  - [Effect evaluation of a 2 dose varicella vaccine immunization strategy
      implemented to control outbreaks in school and kindergarten settings].
AB  - OBJECTIVE: To evaluate the effect of outbreaks control in school settings after a
      2 dose varicella vaccine immunization strategy implemented in Beijing. METHODS:
      Epidemiological data of varicella outbreaks in school and kindergarten settings,
      which were reported by all 16 districts (county) during 2007-2013 according to
      the technical management norms of Beijing, was collected. The first dose and
      second dose varicella vaccine coverage rate of eligible children after the 2 dose
      varicella vaccine immunization strategy implementation were estimated through
      BJIIMS. Based on above we analyzed the changes of outbreak quantity, case
      quantity and the distribution characteristics between the pre-adjustment era
      (2007-2011 years) and late adjustment era (2013) of the 2 dose immunization
      strategy. RESULTS: In pre-adjustment era (2007-2011 years), an average of 74 (95%
      CI: 60-89) outbreaks was reported and 964 (95% CI: 812-1 116) cases were involved
      per year. In late adjustment era (2013): Outbreaks (35) declined 52.7%, involved
      cases (371) declined 61.5%; Outbreaks epidemic duration shortened from 22 days of
      pre-adjustment era to 18 days; Outbreaks involved 10-24 cases declined 64.7%
      (from 34 to 12); Outbreaks involved >= 25 cases declined 71.4% (from 7 to 2);
      Outbreaks of different school type as well as different regions without exception
      declined dramatically. Cumulative one-dose vaccine coverage in children of 2-6 yr
      of age was 89.6% (812 859/907 579), and cumulative second-dose vaccine coverage
      in children of 4-7 yr of age was 44.3% (289 764/647 732). CONCLUSION:
      Implementation of a 2 dose varicella vaccine immunization strategy effectively
      controlled outbreaks in school and kindergarten settings.

PMID- 26310332
TI  - [A study on the health economic evaluations of prevention of mother-to-child HIV
      transmission in Dehong prefecture, Yunnan province, China from 2004 to 2013].
AB  - OBJECTIVE: To conduct health economic evaluation of the prevention of mother-to
      child HIV among pregnant women in Dehong prefecture, Yunnan province, China from
      2004 to 2013. METHODS: Data on cost were collected mainly from the annual
      prevention of mother-to-child transmission (PMTCT) reporting system of Dehong
      prefecture, and supplemented by HIV PMTCT-related resource allocation data from
      local health bureau. Effectiveness indexes were from local continuous HIV
      surveillance system and annual reported data. Cost-effectiveness and cost-utility
      analysis were used to conduct the health economic evaluation. RESULTS: From 2004
      to 2013, 283980 pregnant women were screened for HIV, 2 059 were detected as
      positive, and the HIV positive rate was 0.73%. The total cost of the PMTCT
      program was 14 227 000 RMB after discounting, and the unit cost of positive case
      finding was 4 200 RMB. A total of 26 cases of adults and 325 infants were avoided
      HIV infection, and the cost-effectiveness ratio (CER) was 40 500 RMB/case. The
      total obtained quality adjusted life years (QALY) from the program was 8 911.5,
      each one of which cost 1 600 RMB/QALY. If the feeding pattern were breast
      feeding, CER would be 42 800 RMB/case and each one of QALY would cost 2 200 RMB.
      CONCLUSION: Based on the cost-effectiveness and cost-utility analysis, the HIV
      PMTCT of Dehong prefecture had economic value, which indicates that continued
      investment is needed to strengthen local HIV PMTCT work.

PMID- 26310333
TI  - [Allocation analysis of central government AIDS special funding in priority sites
      of HIV/AIDS prevention and control].
AB  - OBJECTIVE: To analyze the allocation and trend of central government AIDS special
      funding in 4 priority sites of HIV/AIDS prevention and control across calendar
      years. METHODS: Information about the allocation of central government special
      AIDS funding and cumulative HIV/AIDS survivor numbers of Z city, D prefecture, L
      prefecture and D prefecture were collected until 2013. Data were collected from
      2004-2013 for Z city and D prefecture, and data from 2009-2013 were collected for
      L and Y prefecture. Funding allocation among all working areas and their trend
      over time were analyzed. RESULTS: From 2004-2013, the total amount of special
      funding in Z prefecture was 110.15 million RMB. The largest three areas of
      allocation were key population response (29%, 3 190/11 015), surveillance and
      testing (23%, 2 535/11 015) and human resource (13%, 1 498/11 015). The least
      area of allocation was follow-up and prevention of discordant couple transmission
      (2%, 251/11 015). The total amount of special funding in D prefecture from 2004
      2013 was 109.77 million RMB. The largest three areas of allocation were treatment
      and care (25%, 2 691/10 977), follow-up and prevention of discordant couple
      transmission (17%, 1 843/10 977) and surveillance and testing (15%, 1 656/10
      977). The least area was blood safety (1%, 135/10 977). From 2009 to 2013, the
      total amount of special funding in L prefecture was 55 million RMB. The largest
      three areas of allocation were surveillance and testing (60%, 3 298/5 500), high
      risk population intervention (14%, 768/5 500) and follow up and prevention of
      discordant couple transmission (12%, 675/5 500). The least area was blood safety
      (0.1%, 8/5 500). From 2009-2013, the total amount of special funding in Y
      prefecture was 55 million RMB and the largest three areas of allocation were
      project management and others (28%, 1 527/5 500), key population response (19%, 1
      046/5 500) and high risk population intervention (17%, 922/5 500). The least area
      of special funding was blood safety (2%, 106/5 500). Among three HIV/AIDS
      epidemic related key areas (surveillance and testing, follow-up and prevention of
      discordant couple transmission, treatment and care), 2004-2013, allocated funds
      were between 2.96-3.36, 0-0.37, 0.37-1.97 million RMB in Z city; 0.64-2.35, 0.00
      3.00, 2.00-4.70 million RMB in D prefecture; 2009-2013, allocated funds were
      between 2.67-8.85, 0.41-2.39, 0.35-1.84 million RMB in L prefecture, 1.18-2.84,
      0.70-1.05, 0.46-0.89 million RMB in Y prefecture. CONCLUSION: The allocation
      patterns of central government AIDS special funding among key working areas were
      different across 4 different sites; in each individual site, the trend of special
      funding allocation was stable among HIV epidemic related key areas over calendar
      years.

PMID- 26310334
TI  - [A cost-utility study on HIV/AIDS 'one-stop service' pilot at county level].
AB  - OBJECTIVE: To conduct a cost utility study on the HIV/AIDS 'one-stop service' at
      county level. METHODS: Financial records and questionnaires were used to collect
      the information about the resource allocation and the effectiveness of antivirus
      treatment (ART) during the two period which were January 2012-June 2013 and July
      2013-December 2013 in the three pilot counties providing 'one-stop service'.
      Treeage Pro 2009 was used to build the Markov model to simulate the evolution of
      5 different HIV statuses, including HIV infection, AIDS, HIV infection receiving
      ART, AIDS receiving ART and death. And compared the cost-utility ratios between
      current ART process and 'one-stop service' process. National and local epidemic
      data and literature review were used to provide the parameters in the model,
      including prior probabilities of each status, transferring probabilities among
      each status, health utility values and investments of each status and discount
      rate. RESULTS: The expenditures related with 'one-stop service' in the three
      counties were 2 627 339, 209 969, and 191 658 RMB, respectively between July and
      December, 2013. The average periods from HIV infection confirmation to ART
      initiation was reduced from 8 weeks to 18, 10 and 16 days, respectively. The
      percentage of receiving ART within 30 d among those qualified were increased from
      46.7% (63/135) to 64.3% (45/70) in county A, from 40.0% (16/40) to 69.4% (25/36)
      in county B, and from 9.5% (4/42) to 50.0% (19/38) in county C. If current
      process was applied, the CUR in three counties would be 10 391.89 RMB/quality
      adjusted life years (QALY), 6 271.42 RMB/QALY and 3 515.94 RMB/QALY, and these
      would be 10 825.08 RMB/QALY, 8 522.30 RMB/QALY and 10 414.65 RMB/QALY with
      application of 'one-stop service'. CONCLUSION: 'one-stop service' could decrease
      the interval between HIV infection confirmation and ART initiation and increase
      the percentage of receiving ART among people living with HIV(PLHIV), more QALYs
      would be obtained with more resources invested.

PMID- 26310335
TI  - [Impacts of antiretroviral treatment on drug use and high risk sexual behaviors
      among HIV-positive MMT clients].
AB  - OBJECTIVE: To explore the impacts of antiretroviral treatment on drug use and
      high risk sexual behaviors among HIV-positive MMT clients. METHODS: A cross
      sectional study was conducted in patients undergoing ART (ART-experienced) and
      patients not undergoing ART (ART-naive) attending MMT in 5 clinics in Yunnan
      Honghe and Dehong prefectures in 2014. A questionnaire was designed to collect
      socio-demographic characteristics, ART and MMT information and sexual and drug
      use behaviors within 3 months before the investigation was conducted. Logistic
      regression analysis was conducted to identify the predictors for drug use and
      risky sexual behaviors. RESULTS: A total of 328 cases were included in the
      analysis, among which 202 were ART-experienced and 126 were ART-naIve. Among 152
      respondents who were sexually active, 61 (40.1%) reported having unprotected sex
      (UPS) with their regular partners in the prior 3 months. A total of 57.6%
      (189/328) of the respondents used drugs in the prior 3 months. Multiple logistic
      regression analysis revealed that younger than 35 years old (OR = 3.57, 95% CI:
      1.23-10.37), fertility desire (OR = 4.47, 95% CI: 1.49-13.41), partner being HIV
      positive (OR = 4.62, 95% CI: 1.80-11.86), length of MMT attendance less than 5
      years (OR = 2.92, 95% CI: 1.14-7.53), agreed that it was necessary to use condom
      no matter the viral load is high or low (OR = 0.14, 95% CI: 0.04-0.51) were
      protective factors of UPS in the prior 3 months. Multiple logistic regression
      analysis revealed that being Han (OR = 0.46, 95% CI: 0.24-0.89), feeling having
      good health status (OR = 0.39, 95% CI: 0.18-0.85), being enrolled in ART (OR =
      0.32, 95% CI: 0.17-0.60) were protective factors for drug use in the prior three
      months, having contact with drug using friends (OR = 4.41, 95% CI: 2.31-8.29),
      having experience of missing an MMT dose (OR = 3.47, 95% CI: 1.92-6.29), and not
      satisfied with current MMT dose (OR = 13.92, 95% CI: 3.24-59.93) were risk
      factors for drug use during the prior three months. CONCLUSION: ART was not
      associated with risky sexual behavior and drug use in the prior 3 months in this
      population. Future interventions should promote ART among this population, and
      provide education at the same time to prevent the emergence of cross infections
      and drug-resistant strains.

PMID- 26310336
TI  - [A study on the risk and its determinants of HIV transmission by syringe sharing
      among HIV-positive drug users].
AB  - OBJECTIVE: To understand the risks and associated factors of HIV transmission by
      sharing syringes among HIV-positive drug users. METHOD: The survey was conducted
      among HIV-positive injecting drug users (IDUs-HIV+) who received HIV counseling,
      testing and treatment in Changsha city Infectious Disease Hospital and Hengyang
      city No.3 People's Hospital from July 2012 to May 2013 to understand their socio
      demographic characteristics, HIV prevalence and syringe sharing. A total of 503
      IDUs-HIV+ were involved in and provided the contact list of 2 460 drug users who
      had the syringe sharing experience over one month with IDUs-HIV+. 420 IDUs-HIV+
      among 503 were defined as infection sources due to sharing syringe with at least
      one drug user. Among them, 234 HIV-negative persons were in control group, and
      186 HIV-positive were in cased group. A total of 1 220 drug users were followed
      up among 2 460 and defined as vulnerable population. The HIV transmission rate
      was calculated based on the HIV prevalence among vulnerable population. Based on
      the result of HIV transmission to vulnerable population from 420 infection
      sources, case-control study and the multivariate logistic regression analysis
      were adopted to explore the associated factors of HIV transmission among IDUs
      HIV+. RESULTS: As the sources of HIV transmission, 420 IDUs-HIV+ had an average
      duration of (4.5 +/- 1.2) years for drug use. As a susceptible population, 1 220
      drug users sharing syringes with the 420 IDUs-HIV+ had an average duration of
      (1.1 +/- 0.5) years for drug use. There were 238 HIV-positive persons among 1 220
      vulnerable drug users, with a transmission rate of 0.57. In the case-control
      study, the proportion of male subjects was 87.1% (162/186) in the case group,
      which was higher than that in the control group (77.8%, 182/234). The proportion
      of subjects who received support after knowing their HIV infection status was
      51.1% (95/186) in the case group, which was lower than that in the control group
      (79.5%, 186/234). The proportion of subjects sharing syringes every time of using
      drugs was 47.8% (89/186) in the case group, which was higher than that in the
      control group (36.8%, 86/234). The proportion of subjects having AIDS awareness
      was 21.0% (39/186) in the case group, which was lower than that in the control
      group (64.5%, 151/234); the proportion of subjects having close contact with HIV
      positive persons for more than 106 days was 60.2% (112/186) in the case group,
      which was higher than that in the control group (31.6%, 74/234). The proportion
      of subjects maintaining the original drug use method after being infected with
      HIV was 50.5% (94/186) in the case group, which was higher than that in the
      control group (16.7%, 39/234) (all P values < 0.05). The multivariate logistic
      regression analysis was carried out to analyse high correlate factors of HIV
      transmission by sources of transmission, and the AIDS awareness, duration of
      contact between sources of transmission and vulnerable population, access to
      support following confirmed HIV infection were protective factors, OR (95% CI)
      values were 0.155 (0.104-0.262), 0.170 (0.106-0.253), and 0.306 (0.189-0.450),
      respectively; while the frequency of syringe sharing and continuous drug use
      after being infected with HIV were risk factors, and the OR (95% CI) values were
      3.06 (1.77-5.29), and 3.54 (2.16-5.80), respectively. CONCLUSION: HIV
      transmission by IDUs-HIV+ might be contained by raising AIDS awareness, providing
      comprehensive psychological support, conducting needle exchange and methadone
      maintenance treatment and reducing syringe sharing.

PMID- 26310337
TI  - [The survival and development conditions of community-based organizations for
      HIV/AIDS prevention and control among men who have sex with men in three Chinese
      cities].
AB  - OBJECTIVE: To investigate the survival and development conditions of community
      based organizations (CBOs) for HIV/AIDS prevention and control among men who have
      sex with men (MSM) in Chinese cities including Shanghai, Hangzhou, Chongqing.
      METHODS: This study employed both qualitative (focus groups) and quantitative
      (questionnaire survey) methods to obtain information from 15 MSM CBOs in three
      Chinese cities. RESULTS: The mean work time of the 15 CBOs for HIV/AIDS
      prevention and control among MSM was 6.7 years (2.1-11.3 years), and the majority
      of their funds was from international cooperation projects (80 447 000 RMB,
      73.0%) from 2006 to 2013. The survival cost of MSM CBOs apart from expenditure of
      activities was 2 240-435 360 RMB per year. As it was shown in the graph, the
      survival and development of MSM CBOs was closely related to the development of
      international cooperation projects. There was a few small size MSM CBOs taking
      part in the prevention and control of HIV/AIDS and their work content was limited
      before 2006. From 2006 to 2008, some international cooperation projects were
      launched in China, such as the China Global Fund AIDS project and the China-Gates
      Foundation HIV Prevention Cooperation program. As a result, the number of MSM
      CBOs was increased sharply, and both the scale and 2012, the performance of these
      programs further promote the establishment of new MSM CBOs and the development of
      all MSM CBOs with regard to the work places, full-time staffs, work contents,
      work patterns and the specific targeted population. After 2012, most
      international cooperation programs were completed and the local department of
      disease prevention and control continued to cooperate with MSM CBOs. However, the
      degree of support funds from the local department was different among different
      regions. Where the funds were below the half of program funds, the development of
      MSM CBOs ceased and work slowed down. Besides, there were still some constraints
      for the survival and development of MSM CBOs, such as insufficient funds, no
      legitimate identity, the outflow of talents and the unsustainable development.
      CONCLUSION: The survival and development of MSM CBOs was closely related to the
      development of international cooperation projects in China. Some departments of
      disease prevention and control took over the cooperation with MSM CBOs when the
      international cooperation projects were completed. Given the survival cost of MSM
      CBOs and the constraints of MSM CBOs development, it needs further investigation
      on how to ensure the local departments of disease prevention and control to take
      over the cooperation with MSM CBOs and how to cooperate with MSM CBOs.

PMID- 26310338
TI  - [Analysis of perfluoroalkyl substances and their precursors in eighteen market
      milk].
AB  - OBJECTIVE: To explore the level of perfluoroalkyl substances (PFASs) and their
      precursors in 18 market milk samples of China. METHOD: The 18 milk samples were
      selected in 8 provinces of China, including Ningxia, Neimeng, Beijing, Tianjin,
      Hebei, Shanxi, Chongqing, and Guangdong. 8 PFASs and 11 PFAS precursors were
      measured by ultra-high performance liquid chromatography-tandem quadruple mass
      spectrometry (UPLC-MS/MS). The dietary exposure assessment was made. RESULTS:
      Three PFASs were detected in milk samples which were PFOA, PFUdA, and PFOS. The
      numbers of detected samples were 5, 12, and 14, respectively. Their concentration
      ranges were < Limit of determination (LOD)-431.94 pg/ml, < LOD -15.95 pg/ml and <
      LOD -126.98 pg/ml, respectively. Three PFAS precursors were also found above the
      detection limits, namely, 4:2 FTS, 6:2 FTS, and 6:2 diPAP. Only one sample was
      detected 4:2 FTS at the concentration of 3.75 pg/ml. The detected samples of 6:2
      FTS and 6:2 diPAP were 12 and 3. Their concentration ranges were < LOD -2.49
      pg/ml and < LOD -24.56 pg/ml, respectively. The ranges estimated daily intake of
      PFOA and PFOS of the detected samples were 2.49 * 10-3-405.89 * 10-3 ng . kg-1 .
      d-1 and 36.10 * 10-3-119.32 * 10-3 ng . kg-1 . d-1. CONCLUSION: Our results
      suggested that there were different contamination levels of PFASs and their
      precursors in the 18 market milk produced from different regions in china. The
      estimated daily intake of PFASs from the milk in our study were far below the
      tolerable daily intake set by European Union (PFOS: 150 ng . kg-1 . d-1, PFOA: 1
      500 ng . kg-1 . d-1).

PMID- 26310339
TI  - [Analysis of perfluoroalkyl substances precursors in human milk from 12 provinces
      of China].
AB  - OBJECTIVE: To explore the level of perfluoroalkyl substances (PFASs) precursors
      in Chinese human milk samples. METHODS: The human milk samples were collected
      during the performance of Stockholm convention on survey of human milk in China
      in 2007. Based on the geographical location and dietary habits, China was divided
      into the south area and north area which 6 provinces were chosen from each area
      and there were 12 provinces in all. In each province, one urban site and two
      rural sites were selected to collect 80-110 samples. Mothers were randomly
      selected in each site to collect their breast milk. There were 1 237 individual
      human milk samples in all. For each province, the individual samples from the
      urban areas and the rural areas were pooled separately resulting in 24 pooled
      human milk samples. 11 PFAS precursors were measured in pooled samples by ultra
      high performance liquid chromatography-tandem quadruple mass spectrometry (UPLC
      MS/MS). The dietary exposure assessment of newborns was made. RESULTS: Three PFAS
      precursors were found above the detection limits, namely, 6:2 FTS, FHUEA, and 6:2
      diPAP. Their concentration ranges were < Limit of determination (LOD) -47.46
      pg/ml, < LOD -70.68 pg/ml and < LOD -35.08 pg/ml, respectively. The highest total
      PFAS precursor concentration 77.70 pg/ml was found in urban area samples from
      Shannxi Province. Rural area samples from Hubei had the lowest total PFAS
      precursor concentration, which was below the LOD. There were significant
      differences between rural and urban areas in many provinces, such as Shannxi
      (rural: 1.51 pg/ml; urban: 77.70 pg/ml), Shanghai (rural: 1.13 pg/ml; urban:
      71.88 pg/ml), Jiangxi (rural: 65.39 pg/ml; urban: 0.55 pg/ml) and so on. The
      ranges estimated daily intake of 6:2 FTS, FHUEA and 6:2 diPAP of the samples from
      12 provinces were 0.05-4.51, 1.13-6.72 and 1.15-3.34 ng . kg-1 . d-1. CONCLUSION:
      The results suggested the human exposure of PFAS precursors in China and the
      potential health impact of postnatal exposure through breastfeeding to infants.
      The level of PFAS precursors showed differences in regions, rural and urban
      places.

PMID- 26310340
TI  - [Clinical characteristics of hospitalized severe acute respiratory illnesses
      (SARI) in children and risk factors analysis of severe illness: results from SARI
      patients under 15-year-old of sentinel surveillance in 10 cities, China].
AB  - OBJECTIVE: To investigate clinical and epidemiological characteristics of
      hospitalized severe acute respiratory illnesses (SARI) patients under 15 years
      old registered by sentinel hospitals at 10 cities and risk factors analysis of
      severe illness. METHODS: The objects of this study were 2 937 SARI patients under
      15 years old registered by sentinel surveillance in internal wards, pediatrics
      wards and intensive care units (ICU) of 10 sentinel hospitals in 10 cities during
      the period from December 2009 to June 2014. We also collected case report form
      (CRF) of them and their throat swabs for influenza testing. The inclusion
      criteria was hospitalized patients who were admitted by surveillance departments,
      registered by SARI surveillance system, under 15 years old, meeting SARI case
      definition and with complete CRF. Rank-sum test was used to compare the
      difference of age, the duration including from onset to admission, hospital stay
      and from onset to discharging/death between mild illness and severe illness. Chi
      square test was used to compare the difference of demographic characteristics,
      influenza psoitive rate, vaccination rate of influenza, chronic medical
      conditions and clinical characteristics between mild illness and severe illness.
      Logistic regression was used to analysis risk factors associated with severe
      illness by two stratifications from SARI surveillance protocol (< 2 years old and
      >= 2 years old). RESULTS: Among 2 937 SARI patients under 15 years old, 97.7% (2
      872/2 937) was mild illnesses, and 2.3% (65/2 937) was severe illnesses. 78.8% (2
      315/2 937) was under 5 years old. The median ages of severe illness and mild
      illness were 0.4 and 2.0 years old (U = -6.23, P < 0.001). The proportions of
      severe illness and mild illness with at least one chronic medical condition were
      32.3% (21/65) and 8.4% (240/2 872) (chi2 = 45.03, P < 0.001). The positive rate
      of influenza virus was 6.5% (190/2 937), which was 6.5% (186/2 858) for mild
      illness and 6.2% (4/65) for severe illness (chi2 = 0.08, P = 0.961). The
      proportion of seasonal influenza vaccination was 1.5% (42/2 853), which was 1.5%
      (42/2 788) for mild illness and higher than that for severe illness (0) (chi2 =
      6.09, P = 0.048). For under 2 years old patients, age < 11 months and with at
      least one chronic medical condition were risk factors for severe SARI illness,
      and the risk for SARI patients who was 12-23 months and without medical condition
      was 14.71 (5.35-40.44) and 5.61 (2.96-10.63). For >= 2 years old patients, age,
      with at least one chronic medical condition and seasonal influenza vaccination
      history have no association with severe illness, OR (95% CI) was 0.92 (0.80
      1.05), 0.67 (0.09-5.05) and 0.85 (0.31-2.35), respectively. CONCLUSION: Most of
      SARI patients registered by 10 urban sentinel hospitals were patients under 5
      years old. Age < 11 months and with at least chronic medical conditions were
      possible risk factors of severe illness of SARI patients.

PMID- 26310341
TI  - [Investigation on under-reported deaths in Xuanwei Yunnan province, during 2011
      2013].
AB  - OBJECTIVE: To evaluate the completeness of the death registration system, so as
      to understand the death patterns in Xuanwei. METHODS: The investigation on under
      reported deaths was conducted in 30 villages selected with a multi-stage random
      sampling strategy. Participants were asked about changes of their family members
      (family members born or dead) during past 3 years with door to door visit. Then,
      death cases obtained in our investigation were matched with those from routine
      death registration system and under-reported rate of deaths during 2011-2013 was
      calculated employing capture-recapture method. RESULTS: Total under-reported rate
      of deaths was 31.88%. For people aged between 0-14, 15-39, 40-69 and 60 above,
      under-reported rates of death were 33.35%, 34.93%, 29.10%, and 32.88%,
      respectively. And they were 31.72% and 32.02% for males and females,
      respectively. There was no significant difference shown in under-reported rates
      among deaths in different age groups (chi2 = 7.24, P = 0.065) and genders (chi2 =
      0.06, P = 0.803). The under-reported rates in high-mortality, medium-mortality
      and low-mortality regions were 17.48%, 38.01%, and 36.22%, respectively with a
      significant difference (chi2 = 213.25, P < 0.001). Death in local regions with
      mortality rate higher than 600.00/10(5), between 400.00/105 and 600.00/105 and
      lower than 400.00/105 were adjusted with under-reported rates in three regions
      above respectively. The total adjusted morality rate in Xuanwei during 2011-2013
      was 776.47/105. For males and females, they were 918.73/105 and 617.46/105,
      respectively. CONCLUSION: Overall under-reported rate of death was high in death
      registration system in Xuanwei. It was necessary to adjust mortality data
      reported with under-reported rate of death to estimate death patterns in this
      area.

PMID- 26310342
TI  - [Regulation of alpha-tocopherol on NFkappaB and Nrf2 signaling pathway at early
      stage of N-nitrosomethylbenzylamine?induced human esophageal cell
      carcinogenesis].
AB  - OBJECTIVE: To investigate the regulation of alpha-Tocopherol on NFkappaB and Nrf2
      signaling pathway at early stage of N-nitrosomethylbenzylamine (NMBzA)-induced
      human esophageal carcinogenesis. METHODS: Human normal esophageal HET-1A cells
      were treated with NMBzA at 50 umol/L, 100 umol/L for 24 h to intimate the
      initiation of esophageal carcinogenesis. For intervention groups, HET-1A cells
      were pre-treated with alpha-T at 25, 50, 100 umol/L for 3 h and then co-treated
      with NMBzA (100 umol/L) for 24 h. In comparison with HET-1A cells, human
      esophageal cancer EC109 cells were treated with alpha-T at corresponding
      concentrations. Cells treated with 0.1% DMSO were used as negative control.
      Immunofluorence staining was used for the determination of distribution and
      activation of NFkappaB p65 and Nrf2 in the cell. Real time PCR and Western blot
      were used to determine the expression levels of target genes including cyclinD1,
      KI67, proliferating cell nuclear antigen (PCNA), cyclo-oxygen-ase 2 (COX2), 5LOX,
      HO-1, NQO1 and GCLC. Flow cytometry was utilized to analyze the reactive oxygen
      species contents in the cells. RESULTS: As compared to the control group (1.00 +/
      0.08), the expression of CyclinD1 (2.99 +/- 0.15), KI67 (2.35 +/- 0.38) and PCNA
      (2.46 +/- 0.25) in HET-1A were all markedly increased by NMBzA treatment (F
      values were 97.23, 65.28, 34.62, P < 0.001). Also, the proportion of cells with
      nucleus translocation of NFkappaB p65 (71.0%, 98/138) or Nrf2 (36.3%, 49/135)
      were significantly increased (chi2 values were 194.71, 133.72, P < 0.001), and
      the expression of COX2 (3.22 +/- 0.17), 5LOX (2.87 +/- 0.12) as well as HO-1
      (1.87 +/- 0.22), NQO1 (2.14 +/- 0.08), GCLC (2.63 +/- 0.41) at protein levels
      were elevated (F values were 72.35, 43.87, 69.23, 71.34, 85.79, P values were
      0.013, 0.015, 0.010, 0.011, 0.002). Under the treatment with 50 umol/L alpha-T,
      comparing with the control group(59.1%,65/110),the nuclear translocation of
      NFkappaB p65 (77.7%, 8/104) was clearly inhibited (chi2 = 148.1, P < 0.001), and
      protein expression levels of COX2 (0.74 +/- 0.19) and 5LOX (0.42 +/- 0.13) were
      decreased (F values were 56.31, 73.25, P values were 0.003, 0.001). However, no
      changes on Nrf2 signaling pathway were observed; alpha-T showed little impact on
      NFkappaB or Nrf2 pathway in EC109 cells. CONCLUSIONS: At the early stage of NMBz
      induced esophageal cancer, alpha-T could block the initiation of carcinogenesis
      through suppressing the activation of NFkappaB signaling pathway. It might be the
      major mechanism by which alpha-T is potentially chemopreventive to esophageal
      cancer. During the progression of esophageal cancer, the cells may acquire the
      adaptive functions to accommodate oxidative stress via activating Nrf2 pathway.

PMID- 26310343
TI  - [Development of gas chromatography-mass spectrometry for determination of fatty
      acid esters of chloropropanols in milk powder and the pollution level of infant
      formula].
AB  - OBJECTIVE: To establish a method for determination of fatty acid esters of
      chloropropanols (chloropropanols esters) in milk powder by isotope dilution-gas
      chromatography-mass spectrometry (GC-MS), and to acquire the pollution level of
      chloropropanols esters in infant formula and evaluate the dietary exposure risk
      of chloropropanols esters in infant formula for infants. METHODS: A total of 111
      infant formula samples were collected from supermarkets in Beijing, and the
      infant formula with no chloropropanols esters detected was served as the blank
      sample. The samples were ultrasonically extracted with hexane, followed by ester
      bond cleavage reaction with sodium methylate-methanol and purification by matrix
      solid-supported liquid-liquid extraction, then being derivatived with heptafluoro
      butyrylimidazol. After extracted by sodium chloride solution, the derivatives
      were determined by GC-MS. The concentration of chloropropanols esters were
      quantified using the deuterium chloropropanols esters as the internal standards.
      The accuracy of the method was assessed by the recoveries of the blank spiked
      samples, and the relative standard deviations (RSD) of the recoveries represent
      the precision of the method. The contamination level of chloropropanols esters
      and the intake amount of the infant formula of the 6-month infant were used to
      estimate the dietary exposure assessment, and x (95% CI) and P97.5 of the
      contamination level of chloropropanols esters were used to represent the average
      dietary exposure and the high-end dietary exposure. RESULTS: The satisfied linear
      correlations in the range of 0.010-0.800 mg/L was acquired for 3-MCPD esters, 2
      MCPD esters, 1,3-DCP esters and 2,3-DCP esters with coefficient correlations of
      0.999 9, 0.999 8, 0.999 5 and 0.999 6, respectively. The limits of detection
      (LOD) and the limits of quantitation (LOQ) for 3-MCPD esters, 2-MCPD esters, 1,3
      DCP esters and 2,3-DCP esters were 0.005, 0.005, 0.015, 0.015 mg/kg, and 0.015,
      0.015, 0.045, 0.045 mg/kg. The average recoveries of the four chloropropanols
      esters spiked at 0.025, 0.050 and 0.100 mg/kg in blank matrix were in a range
      from 80.3% to 111.9%, with relative standard deviations (RSD) less than 11.4%. Of
      the 111 infant formula samples, the detection rates and the contamination levels
      of 3-MCPD esters and 2-MCPD esters were 77.5% (86/111), 11.7% (13/111) with the
      contamination levels in the range of ND-0.230 mg/kg and ND-0.039 mg/kg,
      respectively, and chi (95% CI) and P97.5 of 3-MCPD esters and 2-MCPD esters were
      0.020 (0.003-0.113) and 0.006 (0.005-0.025) mg/kg, 0.113 and 0.025 mg/kg,
      respectively. 1,3-DCP esters and 2,3-DCP esters were not detected in the 111
      samples. x (95% CI) and P75 of the six-month old infants to 3-MCPD esters were
      0.304 (0.038-1.735) and 1.735 ug . kg-1 . d-1, respectively, which accounted for
      15.2% and 86.7% of the PMTDI (2 ug . kg-1 . d-1) of 3-MCPD. CONCLUSION: This GC
      MS method was accurate and rugged for the determination of chloropropanols esters
      in milk powder. Based on the exposure assessment results, the health risk of
      chloropropanols esters for infants caused by the intake of infant formula was
      acceptable.

PMID- 26310344
TI  - [Re-examination sampling methods of national immunization survey for national
      immunization program vaccines coverage at the township level by the national
      level in 2013, China].
AB  - OBJECTIVE: To review the re-examination sampling method and procedure of national
      immunization survey for the national immunization program vaccines coverage at
      the township level by the national level in 2013, China. METHODS: According to
      the result of immunization coverage at the township level through self-assessment
      by county, all townships were stratified by whether a township with >= 90%
      immunization coverage for the second dose of measles-containing vaccines (MCV2),
      and a township was urban or rural. After then, 2 townships for each province were
      randomly sampled from those strata through the surveyselect procedure of the
      statistics analysis system 9.2 (SAS 9.2). RESULTS: 64 townships were randomly
      sampled from 32 provincial units for the re-examination, i.e. an urban township
      and a rural township each province, of which there were 38 townships with >= 90%
      MCV2 coverage and 26 townships with < 90% MCV2 coverage. There were 24 urban
      townships, 2 rural townships with < 90% MCV2 coverage and 8 urban townships, 30
      rural townships with >= 90% MCV2 coverage, respectively. CONCLUSIONS: Based on
      the information of the self-assessment result of immunization coverage survey by
      counties, Stratified randomized sampling were employed for the re-examination
      through the Surveyselect procedure of statistics analysis system (SAS) to
      implement the sampling procedure. This can enhance the sampling efficiency,
      ensure the randomness of the sample, and make the survey much more representative
      and comparable.

PMID- 26310345
TI  - [Genotyping of Mycobacterium tuberculosis isolates circulating in Qinghai
      province by spoligotyping].

PMID- 26310346
TI  - [Research on acute non-viral respiratory tract infection pathogens spectrum of
      four hundred influenza-like cases].

PMID- 26310347
TI  - [Molecular typing and clinical epidemiological profile of human adenovirus
      infection among children with severe acute respiratory infection].

PMID- 26310348
TI  - [Analysis of sentinel HIV-1 prevalences and incidences among pregnant women in
      Yunnan province during 2001-2010].

PMID- 26310349
TI  - [Survey on birth defects related knowledge among women of childbearing age in
      Tibetan autonomous region].

PMID- 26310350
TI  - [Investigation and response for the first case of group X meningococcal disease
      in Zhejiang province].

PMID- 26310351
TI  - [Google Flu Trends--the initial application of big data in public health].
AB  - Google Flu Trends (GFT) was the first application of big data in the public
      health field. GFT was open online in 2009 and attracted worldwide attention
      immediately. However, GFT failed catching the 2009 pandemic H1N1 and kept
      overestimating the intensity of influenza-like illness in the 2012-2014 season in
      the United States. GFT model has been updated for three times since 2009, making
      its prediction bias controlled. Here, we summarized the mechanism GFT worked, the
      strategy GFT used to update, and its influence on public health. 

PMID- 26310352
TI  - Correlation between upper limb function and oral health impact in stroke
      survivors.
AB  - [Purpose] The aim of the present study was to evaluate the relationship between
      upper limb impairment and oral health impact in individuals with hemiparesis
      stemming from a stroke. [Subjects and Methods] The study subjects were conducted
      with a sample of 27 stroke survivors with complete or partial hemiparesis with
      brachial or crural predominance. The 14-item short version of the Oral Health
      Impact Profile was used to evaluate perceptions of oral health. The Brazilian
      version of the Stroke Specific Quality of Life Scale was used to evaluate
      perceptions regarding quality of life. [Results] A statistically significant
      association was found between the upper extremity function subscale of the SSQOL
      Brazil and the impact of oral health evaluated using the OHIP-14, with a strong
      correlation found for the physical pain subscale, moderate correlations with the
      functional limitation, psychological discomfort, physical disability, social
      disability and social handicap subscales as well as a weak correlation with the
      psychological disability subscale. Analyzing the OHIP-14 scores with regard to
      the impact of oral health on quality of life, the most frequent classification
      was weak impact, with small rates of moderate and strong impact. [Conclusion]
      Compromised upper limb function and self-perceived poor oral health, whether due
      to cultural resignation or functional disability, exert a negative impact on the
      quality of life of individuals with hemiparesis stemming from a stroke. 

PMID- 26310354
TI  - Digital ischaemia following inadvertent arterial cannulation of a peripherally
      inserted central catheter in a very low birth weight infant.

PMID- 26310353
TI  - Butein sensitizes HeLa cells to cisplatin through the AKT and ERK/p38 MAPK
      pathways by targeting FoxO3a.
AB  - Drug resistance remains a major challenge in cancer therapy. Butein, a
      polyphenolic compound, has been shown to exhibit anticancer activity through the
      inhibition of the activation of the protein kinase B (PKB/AKT) and mitogen
      activated protein kinase (MAPK) pathways, which are two pathways known to be
      involved in resistance to cisplatin. Hence, we hypotheiszed that butein may be a
      chemosensitizer to cisplatin. In the present study, we demonstrated that butein
      synergistically enhanced the growth inhibitory and apoptosis-inducing effects of
      cisplatin on HeLa cells. Moreover, the combination of butein and cisplatin led to
      G1 phase arrest. We then aimed to explore the underlying mechanisms. We found
      that butein inhibited the activation of AKT, extracellular signal-regulated
      kinase (ERKs) and p38 kinases in the presence of cisplatin. The use of the AKT
      inhibitor, LY294002, in combination with cisplatin, induced an increase in
      apoptosis compared to treatment with cisplatin alone, although this effect was
      not as prominent as that exerted by butein in combination with cisplatin. Of
      note, the inhibition of ERK or p38 MAPK by U0126 or SB203580, respectively,
      decreased the apoptosis induced by cisplatin; however, enhanced apoptotic effects
      were observed with the use of ERK/p38 MAPK inhibitor in combination with butein.
      These data suggest that the AKT and ERK/p38 MAPK pathways are involved in the
      synergistic effects of butein and cisplatin. Furthermore, co-treatment with
      butein and cisplatin promoted the nuclear translocation and expression of
      forkhead box O3a (FoxO3 or FoxO3a). FoxO3a may be the key molecule on which these
      pathways converge and is thus implicated in the synergistic effects of butein and
      cisplatin. This was further confirmed by the RNAi-mediated suppression of FoxO3a.
      FoxO3a target genes involved in cell cycle progression and apoptosis were also
      investigated, and combined treatment with butein and cisplatin resulted in the
      downregulation of cyclin D1 and Bcl-2 and the upregulation of p27 and Bax. In
      addition, the combination of both agents markedly inhibited tumor growth and
      increased the expression of FoxO3a in mouse tumor xenograft models of cervical
      cancer. Taken together, to the best of our knowledge, our results reveal for the
      first time that butein sensitizes cervical cancer cells to cisplatin in vitro and
      in vivo, and these effects of butien may be related to the inhibition of the
      activation of the AKT and ERK/p38 MAPK pathways by targeting FoxO3a. 

PMID- 26310355
TI  - Therapeutic Effects of Melatonin On Liver And Kidney Damages In Intensive
      Exercise Model of Rats.
AB  - Extensive exercise induces inflammatory reactions together with high production
      of free radicals and subsequent liver and kidney tissues damage. This study was
      designed to investigate for effects of melatonin on liver and kidney tissues in
      the extensive exercise exposed rats and non-exercised rats. In this research, 24
      male Sprague-Dawley rats were divided into four groups. For exercise rat model,
      the rats were exposed to slow pace running with the velocity of 10 m/min for 5
      minutes for five days just before the study. And for last ten days after
      adaptation period, the exercise was improved as 15 min with the speed of 20 m/min
      and intra-peritoneal melatonin injection has been performed to the melatonin
      treated groups with the dose of 10 mg/kg. Biochemical results revealed a decrease
      in the parameters of kidney and liver enzymes in exercise-group and an increase
      in the parameters of serum, liver and kidney enzymes in the group that melatonin
      exercise-group. As for histological analysis, while it is observed that there are
      cellular degenerations in the liver and kidney tissues with exercise application,
      a decrease has been observed in these degenerations in the group that melatonin
      was applied. At the end of the research, it has been determined that exercise
      application causes some damages on liver and kidney, and these damages were
      ameliorated with melatonin treatment. 

PMID- 26310356
TI  - In vitro DNA binding studies of antiretroviral drug nelfinavir using ethidium
      bromide as fluorescence probe.
AB  - Understanding the interaction of small molecules with DNA has become an active
      research area at the interface between biology and chemistry. In the present
      work, we investigated the mode of interaction of nelfinavir (NFV) with herring
      sperm DNA (hs DNA) under physiological conditions using various biophysical
      techniques. Analysis of UV-absorption and fluorescence spectra indicates the
      formation of complex between NFV and hs DNA. According to the fluorescence
      results, the binding constant (K) between NFV and hs DNA was found to be 3.30 *
      10(4)LM(-1). The calculated thermodynamic parameters (DeltaH degrees  and DeltaS
      degrees ) suggested that hydrogen bonding plays a major role in binding between
      them. Phosphate group binding studies revealed that there was no electrostatic
      interactions occurred between NFV and hs DNA. Circular dichroism (CD) and DNA
      melting curve were employed to measure the conformational change of hs DNA in the
      presence of NFV, which verified the minor groove binding mode. These results were
      further supported by viscosity measurements and competitive displacement assay
      study using Hoechst 33258. According to the sequence specificity experiments, NFV
      binds to A-T rich region of hs DNA.

PMID- 26310357
TI  - Consensus Meeting on "Uric Acid and Cardiovascular Risk" held at University Magna
      Graecia, Catanzaro, Italy, May 2014. Publication of the Proceedings as a special
      issue in the International Journal of Cardiology.
AB  - Introduction to a special supplement issue on the importance of uric acid in
      cardiovascular disorders. 

PMID- 26310358
TI  - Terminal modification of polymeric micelles with pi-conjugated moieties for
      efficient anticancer drug delivery.
AB  - High drug loading content is the critical factor to polymeric micelles for
      efficient chemotherapy. Small molecules of cinnamic acid, 7-carboxymethoxy
      coumarin and chrysin with different pi-conjugated moieties were immobilized on
      the terminal hydroxyl groups of PCL segments in mPEG-PCL micelles to improve drug
      loading content via the evocation of pi-pi stacking interaction between
      doxorubicin (DOX) and polymeric micelles. The modification of pi-conjugated
      moieties enhanced the capability of crystallization of mPEG-PCL block copolymers.
      The drug loading content increased dramatically from 12.9% to 25.5% after
      modification. All the three modified mPEG-PCL micelles were nontoxic to cells.
      Chrysin modified polymeric micelles exhibited the most efficient anticancer
      activity. The in vivo anticancer activity of 10 mg/kg DOX dose of chrysin
      modified micelle formulation for twice injections was comparable to that of 5
      mg/kg dose of free DOX.HCl for four injections under the circumstance of same
      total DOX amount. The systemic toxicity of DOX loaded chrysin modified micelles
      was significantly reduced. This research provided a facile strategy to achieve
      polymeric micelles with high drug loading content and efficient anticancer
      activity both in vitro and in vivo. 

PMID- 26310359
TI  - Tumor-specific penetrating peptides-functionalized hyaluronic acid-d-alpha
      tocopheryl succinate based nanoparticles for multi-task delivery to invasive
      cancers.
AB  - Poor site-specific delivery and incapable deep-penetration into tumor are the
      intrinsic limitations to successful chemotherapy. Here, the tumor-homing
      penetrating peptide tLyP-1-functionalized nanoparticles (tLPTS/HATS NPs),
      composed of two modularized amphiphilic conjugates of tLyP-1-PEG-TOS (tLPTS) and
      TOS-grafted hyaluronic acid (HATS), had been fabricated for tumor-targeted
      delivery of docetaxel (DTX). The prepared tLPTS/HATS NPs had about 110 nm in mean
      diameter, high drug encapsulation efficiency (93%), and sustained drug release
      behavior. In vitro studies demonstrated that the tLPTS/HATS NPs exhibited
      enhanced intracellular delivery and much better anti-invasion ability,
      cytotoxicity, and apoptosis against both invasive PC-3 and MDA-MB-231 cells as
      compared to the non-tLyP-1-functionalized HATS NPs. The remarkable penetrability
      and inhibitory effect on both PC-3 and MDA-MB-231 multicellular tumor spheroids
      were also identified for the tLPTS/HATS NPs. In vivo biodistribution imaging
      demonstrated the tLPTS/HATS NPs possessed much more lasting accumulation and
      extensive distribution throughout tumor regions than the HATS NPs. The higher in
      vivo therapeutic efficacy with lower systemic toxicity of the tLPTS/HATS NPs was
      also verified by the PC-3 xenograft model in athymic nude mice. These results
      suggested that the designed novel tLPTS/HATS NPs were endowed with tumor
      recognition, internalization, penetration, and anti-invasion, and thus might be a
      promising anticancer drug delivery vehicle for targeted cancer therapy. 

PMID- 26310360
TI  - Gene regulation of lipid and phospholipid metabolism in Atlantic cod (Gadus
      morhua) larvae.
AB  - The mechanism of essentiality of dietary phospholipid (PL) for larval fish is not
      clear. The main objective of the present study was to determine if the PL
      requirement of Atlantic cod larvae was due to any genetic impairment caused by
      functional immaturity. Cod larvae were sampled at 1, 3, 8, 13, 17, 18, 30, 42 and
      60 days post hatch (dph) for transcriptome analysis using a recently developed
      microarray. The fatty acid profile and gene expression levels of cod larvae at 17
      dph were compared after feeding differently enriched rotifers, which contained
      different DHA levels in PL. No significant differences (p<0.05) were found for
      the two rotifer diets in the overall gene expression level of cod larvae, their
      growth and survival, and their DHA levels in total lipid and PL fraction. The
      fatty acid data suggested that dietary EPA was elongated to DPA by cod larvae,
      and a threshold DHA level in PL to maintain membrane fluidity and other functions
      may exist. There appeared to be no major effect of development on the expression
      of key genes of PL biosynthesis suggesting no genetic constrain in early
      developmental stages. Our overall data suggested that besides the possible
      limited de novo PC synthesis ability in the intestine, other metabolic
      constraints should also be considered, especially the possible low input of bile
      PC as a result of immature liver. Further studies are needed to elucidate the
      gene expression level and enzyme activity in the PL biosynthesis pathways for
      specific tissue or cells.

PMID- 26310361
TI  - Abcb1 gene expression pattern and function of copper detoxification in Fujian
      oyster, Crassostrea angulata.
AB  - Oysters are considered hyper-accumulators of Cu, but the molecular mechanism by
      which they maintain Cu cell homeostasis is still unclear. ATP-binding cassette
      protein subfamily B member 1 (ABCB1, P-glycoprotein) can transport a variety of
      substrates across the cell membrane in aquatic animals. In this study, to provide
      insight into the roles of ABCB1 in resistance against Cu in oysters, complete
      cDNA of abcb1 gene in Crassostrea angulata was cloned and analyzed. The complete
      sequence of C. angulata ABCB1 showed high identity to ABCB1 from other bivalves
      and contained some classical motifs of ABCB transport proteins. Abcb1 was mainly
      expressed in the apical epithelial cell of gills and epithelia of mantles. Abcb1
      expression and Cu accumulation were also studied in control oysters and oysters
      exposed to Cu (30, 100, 300 MUg/L Cu, 1-15 days). Cu accumulation in the gill and
      mantle were measured after abcb1 gene interference. The complete sequence of C.
      angulata ABCB1 showed high identity to ABCB1 from other bivalves and contained
      some classical motifs of ABCB transport proteins. The mRNA transcript of abcb1
      showed hypersensitivity to Cu exposure. A concentration-dependent highest abcb1
      mRNA level (up to 5.61-fold to the control) in the gill and mantle existed across
      all Cu exposure concentrations after 3 days of Cu exposure. The gill and mantle
      Cu concentration were significantly higher after the abcb1 mRNA interference.
      According to these results, it is here speculated that ABCB1 may underlie cell
      protection against Cu in C. angulata.

PMID- 26310362
TI  - Look for good and never give up: A novel attention training treatment for
      childhood anxiety disorders.
AB  - Attention bias modification training (ABMT) is a promising treatment for anxiety
      disorders. Recent evidence suggests that attention training towards positive
      stimuli, using visual-search based ABMT, has beneficial effects on anxiety and
      attention biases in children. The present study extends this prior research using
      distinctive techniques designed to increase participant learning, memory
      consolidation, and treatment engagement. Fifty-nine clinically anxious children
      were randomly assigned to the active treatment condition (ATC) (N = 31) or
      waitlist control condition (WLC) (N = 28). In the ATC, children completed 12
      treatment sessions at home on computer in which they searched matrices for a
      pleasant or calm target amongst unpleasant background pictures, while also
      engaging in techniques designed to consolidate learning and memory for these
      search strategies. No contact was made with children in the WLC during the wait
      period. Diagnostic, parent- and child-reports of anxiety and depressive symptoms,
      externalising behaviour problems and attention biases were assessed pre- and post
      condition and six-months after treatment. Children in the ATC showed greater
      improvements on multiple clinical measures compared to children in the WLC. Post
      treatment gains improved six-months after treatment. Attention biases for angry
      and happy faces did not change significantly from pre-to post-condition. However,
      larger pre-treatment attention bias towards threat was associated with greater
      reduction in anxiety at post-treatment. Also, children who showed greater
      consolidation of learning and memory strategies during treatment achieved greater
      improvement in global functioning at post-treatment. Attention training towards
      positive stimuli using enhanced visual-search procedures appears to be a
      promising treatment for childhood anxiety disorders.

PMID- 26310363
TI  - Relationships among adaptive and maladaptive emotion regulation strategies and
      psychopathology during the treatment of comorbid anxiety and alcohol use
      disorders.
AB  - Both maladaptive and adaptive emotion regulation strategies have been linked with
      psychopathology. However, previous studies have largely examined them separately,
      and little research has examined the interplay of these strategies cross
      sectionally or longitudinally in patients undergoing psychological treatment.
      This study examined the use and interplay of adaptive and maladaptive emotion
      regulation strategies in 81 patients receiving cognitive-behavioral interventions
      for comorbid alcohol use and anxiety disorders. Patients completed measures of
      emotion regulation strategy use and symptoms of psychopathology pre- and post
      treatment. Cross-sectionally, higher use of maladaptive strategies (e.g., denial)
      was significantly related to higher psychopathology pre- and post-treatment,
      whereas higher use of adaptive strategies (e.g., acceptance) only significantly
      related to lower psychopathology post-treatment. Prospectively, changes in
      maladaptive strategies, but not changes in adaptive strategies, were
      significantly associated with post-treatment psychopathology. However, for
      patients with higher pre-treatment maladaptive strategy use, gains in adaptive
      strategies were significantly associated with lower post-treatment
      psychopathology. These findings suggest that psychological treatments may
      maximize efficacy by considering patient skill use at treatment outset. By better
      understanding a patient's initial emotion regulation skills, clinicians may be
      better able to optimize treatment outcomes by emphasizing maladaptive strategy
      use reduction predominately, or in conjunction with increasing adaptive skill
      use. 

PMID- 26310364
TI  - The risk of diabetes development in long-term observation of patients with acute
      hyperglycaemia during myocardial infarction.
AB  - BACKGROUND: Acute hyperglycemia in patients with myocardial infarction is an
      unfavorable predictive factor. However, there are limited data regarding the
      relationship between acute hyperglycemia and the incidence of new onsets diabetes
      in long-term observation. AIM: We studied the relationship between admission
      glycemia in patients with myocardial infarction and the future development of
      diabetes. METHODS: In 190 patients admitted during 2004-2007 years with
      myocardial infarction diabetes was excluded on the basis of oral glucose
      tolerance test (OGTT) performed at the end of hospitalization. Patients were
      divided into three groups according to admission glucose level: G1 <7.8 mmol/l
      (<140 mg/dl); G2: 7.8-11.0 mmol/l (140-199 mg/dl); G3 >=11.1 mmol/l (>=200
      mg/dl). RESULTS: The groups consisted of 80 (42.1%), 94 (49.5%) and 16 (8.4%)
      patients, respectively for G1, G2 and G3. The mean age was 61.3+/-11.3 years. ST
      segment elevation myocardial infarction (STEMI) was diagnosed in 158 patients
      (83.2%) and non-ST-segment elevation myocardial infarction (NSTEMI) in 32
      patients (16.8%). A total of 15 cases (7.9% of the study group) of newly
      diagnosed diabetes mellitus were registered during a mean follow-up of 48.2+/
      13.9 months. Higher incidence of new diabetes diagnosis was noticed in patients
      with higher glucose level on admission (5.0% vs. 7.4% vs. 25.0%, p=0.0249).
      Regression analysis showed two independent risk factors of diabetes development
      in observational period: admission glucose level considered as continuous
      variable with OR 1.2 (95% CI 1.0-1.4, p=0.03) and occurrence of IGT with OR 3.6
      (95% CI 1.0-12.0, p=0.04). CONCLUSIONS: Patients with acute hyperglycemia during
      myocardial infarction are more likely to have diabetes in future. This group of
      patients requires a close monitoring of glucose metabolism after myocardial
      infarction.

PMID- 26310365
TI  - [History and perspectives of the monocyte-macrophage system].
AB  - The macrophage cell system was identified by Metchnikoff on the basis of its
      phagocytic ability. Later on, the reticulohistiocytic system was defined as being
      composed of antigen-presenting reticulum cells and macrophages. Van Furth
      proposed that the mononuclear phagocyte system includes all tissue macrophages as
      well as antigen-presenting cells and blood monocytes as their precursors. Recent
      findings have shown that blood monocytes are not just transient forms involved in
      the recruitment of macrophages but that different dendritic and monocytic
      subpopulations can be observed in blood. In tissue, self-renewing macrophages
      derived from the yolk sac as well as monocyte-derived dendritic cells and
      monocyte-derived macrophages can be distinguished. Due to their plasticity and
      polarization, under inflammatory conditions monocyte-derived macrophages may be
      beneficial for the reestablishment of homeostasis or may contribute to mostly
      chronic diseases. Because of their ubiquitous distribution, monocytes and
      macrophages are increasingly considered to be possible therapeutic targets. 

PMID- 26310367
TI  - Physiological parameters and protective energy dissipation mechanisms expressed
      in the leaves of two Vitis vinifera L. genotypes under multiple summer stresses.
AB  - Photosynthetic performances and energy dissipation mechanisms were evaluated on
      the anisohydric cv. Sangiovese and on the isohydric cv. Montepulciano (Vitis
      vinifera L.) under conditions of multiple summer stresses. Potted vines of both
      cultivars were maintained at 90% and 40% of maximum water availability from fruit
      set to veraison. One week before veraison, at predawn and midday, main gas
      exchange and chlorophyll fluorescence parameters, chlorophyll content,
      xanthophyll pool and cycle and catalase activity were evaluated. Under water
      deficit and elevated irradiance and temperature, contrary to cv. Montepulciano
      and despite a significant leaf water potential decrease, Sangiovese's leaves kept
      their stomata more open and continued to assimilate CO2 while also showing higher
      water use efficiency. Under these environmental conditions, in comparison with
      the isohydric cv. Montepulciano, the protective mechanisms of energy dissipation
      exerted by the anisohydric cv. Sangiovese were: (i) higher stomatal conductance
      and thermoregulation linked to higher transpiration rate; (ii) greater ability at
      dissipating more efficiently the excess energy via the xanthophylls cycle
      activity (thermal dissipation) due to higher VAZ pool and greater increase of de
      epoxidation activity. 

PMID- 26310368
TI  - Dasatinib Modulates Invasive and Migratory Properties of Canine Osteosarcoma and
      has Therapeutic Potential in Affected Dogs.
AB  - BACKGROUND: This investigation sought to elucidate the relationship between
      hepatocyte growth factor (HGF)-induced metastatic behavior and the tyrosine
      kinase inhibitors (TKIs) crizotinib and dasatinib in canine osteosarcoma (OS).
      Preliminary evidence of an apparent clinical benefit from adjuvant therapy with
      dasatinib in four dogs is described. METHODS: The inhibitors were assessed for
      their ability to block phosphorylation of MET; reduce HGF-induced production of
      matrix metalloproteinase (MMP); and prevent invasion, migration, and cell
      viability in canine OS cell lines. Oral dasatinib (0.75 mg/kg) was tested as an
      adjuvant therapy in four dogs with OS. RESULTS: Constitutive phosphorylation of
      MET was detected in two cell lines, and this was unaffected by 20-nM incubation
      with either dasatinib or crizotinib. Incubation of cell lines with HGF (MET
      ligand) increased cell migration and invasion in both cell lines and increased
      MMP-9 activity in one. Dasatinib suppressed OS cell viability and HGF-induced
      invasion and migration, whereas crizotinib reduced migration and MMP-9 production
      but did not inhibit invasion or viability. CONCLUSIONS: Invasion, migration, and
      viability of canine OS cell lines are increased by exogenous HGF. HGF induces
      secretion of different forms of MMP in different cell lines. The HGF-driven
      increase in viability and metastatic behaviors we observed are more uniformly
      inhibited by dasatinib. These observations suggest a potential clinical benefit
      of adjuvant dasatinib treatment for dogs with OS.

PMID- 26310369
TI  - Expression of DNA Damage Response Molecules PARP1, gammaH2AX, BRCA1, and BRCA2
      Predicts Poor Survival of Breast Carcinoma Patients.
AB  - BACKGROUND: Poly(ADP-ribose) polymerase 1 (PARP1), gammaH2AX, BRCA1, and BRCA2
      are conventional molecular indicators of DNA damage in cells and are often
      overexpressed in various cancers. In this study, we aimed, using
      immunohistochemical detection, whether the co-expression of PARP1, gammaH2AX,
      BRCA1, and BRCA2 in breast carcinoma (BCA) tissue can provide more reliable
      prediction of survival of BCA patients. MATERIALS AND METHODS: We investigated
      immunohistochemical expression and prognostic significance of the expression of
      PARP1, gammaH2AX, BRCA1, and BRCA2 in 192 cases of BCAs. RESULTS: The expression
      of these four molecules predicted earlier distant metastatic relapse, shorter
      overall survival (OS), and relapse-free survival (RFS) by univariate analysis.
      Multivariate analysis revealed the expression of PARP1, gammaH2AX, and BRCA2 as
      independent poor prognostic indicators of OS and RFS. In addition, the combined
      expressional pattern of BRCA1, BRCA2, PARP1, and gammaH2AX (CSbbph) was an
      additional independent prognostic predictor for OS (P < .001) and RFS (P < .001).
      The 10-year OS rate was 95% in the CSbbph-low (CSbbph scores 0 and 1) subgroup,
      but that was only 35% in the CSbbph-high (CSbbph score 4) subgroup. CONCLUSION:
      This study has demonstrated that the individual and combined expression patterns
      of PARP1, gammaH2AX, BRCA1, and BRCA2 could be helpful in determining an accurate
      prognosis for BCA patients and for the selection of BCA patients who could
      potentially benefit from anti-PARP1 therapy with a combination of genotoxic
      chemotherapeutic agents.

PMID- 26310370
TI  - Quantification of Regional Breast Density in Four Quadrants Using 3D MRI-A Pilot
      Study.
AB  - PURPOSE: This study presented a three-dimensional magnetic resonance (MR)-based
      method to separate a breast into four quadrants for quantitative measurements of
      the quadrant breast volume (BV) and density. METHODS: Breast MR images from 58
      healthy women were studied. The breast and the fibroglandular tissue were
      segmented by using a computer-based algorithm. A breast was divided into four
      quadrants using two perpendicular planes intersecting at the nipple or the nipple
      centroid line. After the separation, the BV, the fibroglandular tissue volume,
      and the percent density (PD) were calculated. The symmetry of the quadrant BV in
      the left and right breasts separated by using the nipple alone, or the nipple
      centroid line, was compared. RESULTS: The quadrant separation made on the basis
      of the nipple-centroid line showed closer BVs in four quadrants than using the
      nipple alone. The correlation and agreement for the BV in corresponding quadrants
      of the left and the right breasts were improved after the nipple-centroid
      reorientation. Among the four quadrants, PD was the highest in the lower outer
      and the lowest in the upper outer (significant than the other three) quadrants (P
      < .05). CONCLUSIONS: We presented a quantitative method to divide a breast into
      four quadrants. The reorientation based on the nipple-centroid line improved the
      left to right quadrant symmetry, and this may provide a better standardized
      method to measure quantitative quadrant density. The cancer occurrence rates are
      known to vary in different sites of a breast, and our method may provide a tool
      for investigating its association with the quantitative breast density.

PMID- 26310371
TI  - Percutaneous Transthoracic Lung Biopsy: Comparison Between C-Arm Cone-Beam CT and
      Conventional CT Guidance.
AB  - BACKGROUND: C-arm cone-beam computed tomography (CBCT) is a comparatively novel
      modality for guiding percutaneous transthoracic lung biopsies (PTLBs), and
      despite its potential advantages over conventional computed tomography (CCT), a
      head-to-head comparison of the two techniques has yet to be reported in the
      literature. This study aims to evaluate the diagnostic value and safety of CBCT
      guided PTLB compared to CCT-guided biopsy, with cases performed in a single
      hospital. METHODS: A total of 104 PTLB patients were retrospectively analyzed in
      this study. 35 PTLBs were performed under CBCT guidance, and 69 PTLBs were
      performed under CCT guidance. Diagnostic accuracy, sensitivity, and specificity
      for malignancy as well as procedure time, radiation dose of patients, and
      complication rate in the two groups were compared. RESULTS: Total procedure time
      was significantly lower in the CBCT group (32 +/- 11 minutes) compared to the CCT
      group (38 +/- 9.7 minutes; P = .009), especially among patients >=70 years of age
      (CBCT: 33 +/- 12 minutes, CCT: 42 +/- 13, P = .022). For lesions in the lower
      lobes, the CBCT-guided group received significantly reduced effective radiation
      dose (2.9 +/- 1.6 mSv) than CCT-guided patients (3.7 +/- 0.80; P = .042).
      Diagnostic accuracy, sensitivity, and specificity for malignancy were comparable
      between the two groups, as were post-biopsy complication rates. CONCLUSION: CBCT
      guidance significantly reduces the procedure time and radiation exposure for
      PTLBs compared with CCT, and should be considered in clinical settings that may
      be difficult or time-consuming to perform under CCT.

PMID- 26310372
TI  - Correlation Between Clinical-Pathologic Factors and Long-Term Follow-Up in Young
      Breast Cancer Patients.
AB  - OBJECTIVE: Diagnosis of breast cancer in young patients (<=35) correlates with a
      worse prognosis compared to their older counterparts (>35). The aim of this study
      is to evaluate the relevance of clinical-pathologic factors and prognosis in
      young (<=35) breast cancer patients. METHODS: One hundred thirty-two patients of
      operable breast cancer who were younger than 35 are analyzed in this study. They
      were treated in our hospital between January 2006 and December 2012. Patients are
      classified into four molecular subtypes based on the immunohistochemical profiles
      of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth
      factor receptor 2 (HER2), and Ki-67. Clinical and pathologic factors have been
      combined to define a specific classification of three risk levels to evaluate the
      prognosis of these young women. RESULTS: Patients whose ages are less than 30
      have poorer prognosis than patients whose ages are between 31 and 35. The status
      of lymph nodes post-surgery seems to be the only factor related to patient age in
      young patients. The patients in level of ER+ or PR+ and HER2-/+ status have the
      worst prognosis in hormone receptor-positive breast cancer. Group 3 in risk
      factor grouping has the poorer prognosis than the other two groups. CONCLUSIONS:
      Patient age and axillary lymph nodes post-surgery are the independent and
      significant predictors of distant disease-free survival, local recurrence-free
      survival, and overall survival. The absence of PR relates to poor prognosis. The
      risk factor grouping provides a useful index to evaluate the risk of young breast
      cancer to identify subgroups of patients with a better prognosis.

PMID- 26310373
TI  - Circulating Levels of PAI-1 and SERPINE1 4G/4G Polymorphism Are Predictive of
      Poor Prognosis in HCC Patients Undergoing TACE.
AB  - Although several molecular markers have been proposed as prognostic of disease
      progression in Hepatocellular carcinoma (HCC), predictive markers of response to
      treatment are still unsatisfactory. Here, we propose a genetic polymorphism as a
      potential predictive factor of poor prognosis in HCC patients treated with
      transcatheter arterial chemoembolization (TACE). In particular, we show that the
      guanosine insertion/deletion polymorphism in the promoter region of SERPINE1 gene
      at the -675 bp position, named 4G/4G, predicts poor prognosis in a cohort of 75
      patients with HCC undergoing TACE. By a combination of ELISA and SERPINE1
      promoter study, we found that the presence of elevated plasma levels of
      plasminogen activator inhibitor-1 (PAI-1) in patients with 4G/4G genotype is
      significantly associated with reduced overall survival compared to patients with
      5G/5G or 4G/5G genotype in HCC patients after TACE. Our analysis provided
      evidence that variation in SERPINE1 gene plays a role in defining the outcome in
      patients treated with TACE. In addition to a poor disease outcome, the 4G/4G
      variant represents an unfavorable predictive factor for response to chemotherapy
      as well. 

PMID- 26310374
TI  - Detection of a Distinctive Genomic Signature in Rhabdoid Glioblastoma, A Rare
      Disease Entity Identified by Whole Exome Sequencing and Whole Transcriptome
      Sequencing.
AB  - We analyzed the genome of a rhabdoid glioblastoma (R-GBM) tumor, a very rare
      variant of GBM. A surgical specimen of R-GBM from a 20-year-old woman was
      analyzed using whole exome sequencing (WES), whole transcriptome sequencing
      (WTS), single nucleotide polymorphism array, and array comparative genomic
      hybridization. The status of gene expression in R-GBM tissue was compared with
      that of normal brain tissue and conventional GBM tumor tissue. We identified 23
      somatic non-synonymous small nucleotide variants with WES. We identified the BRAF
      V600E mutation and possible functional changes in the mutated genes, ISL1 and
      NDRG2. Copy number alteration analysis revealed gains of chromosomes 3, 7, and 9.
      We found loss of heterozygosity and focal homozygous deletion on 9q21, which
      includes CDKN2A and CDKN2B. In addition, WTS revealed that CDK6, MET, EZH2, EGFR,
      and NOTCH1, which are located on chromosomes 7 and 9, were over-expressed,
      whereas CDKN2A/2B were minimally expressed. Fusion gene analysis showed 14
      candidate genes that may be functionally involved in R-GBM, including TWIST2, and
      UPK3BL. The BRAF V600E mutation, CDKN2A/2B deletion, and EGFR/MET copy number
      gain were observed. These simultaneous alterations are very rarely found in GBM.
      Moreover, the NDRG2 mutation was first identified in this study as it has never
      been reported in GBM. We observed a unique genomic signature in R-GBM compared to
      conventional GBM, which may provide insight regarding R-GBM as a distinct disease
      entity among the larger group of GBMs. 

PMID- 26310375
TI  - Clinical Significance of IGFBP-3 Methylation in Patients with Early Stage Gastric
      Cancer.
AB  - BACKGROUND: IGFBP-3 is a multifunctional protein that inhibits growth and induces
      apoptosis of cancer cells. Hypermethylation of the promoter represses expression
      of the IGFBP-3 gene. We undertook this study to assess the impact of IGFBP-3
      methylation on survival of early stage gastric cancer patients. METHODS: Of the
      482 tissue samples from gastric cancer patients who underwent curative surgery,
      IGFBP-3 methylation was tested in 138 patients with stage IB/II gastric cancer.
      We also analyzed IGFBP-3 methylation in 26 gastric cancer cell lines. IGFBP-3
      methylation was evaluated by methylation-specific polymerase chain reaction
      (MethyLight). Statistical analyses, all two-sided, were performed to investigate
      the prognostic effects of methylation status of the IGFBP-3 promoter on various
      clinical parameters. RESULTS: Hypermethylation of IGFBP-3 was observed in 26
      (19%) of the 138 stage IB/II gastric cancer patients. Clinicopathological factors
      such as age, Lauren classification, sex, tumor infiltration, lymph node
      metastasis, and histologic grade did not show a statistically significant
      association with the methylation status of the IGFBP-3 promoter. Patients with a
      hypermethylated IGFBP-3 promoter had similar 8-year disease-free survival
      compared with those without a hypermethylated IGFBP-3 promoter (73% vs 75%, P =
      .78). In subgroup analyses, females, but not males, seemed to have poorer
      prognosis for DFS and OS in the subset of patients with IGFBP-3 methylation as
      compared with those without IGFBP-3 methylation (8-year DFS: 55.6% vs 71.6%, P =
      .3694 and 8-year overall survival: 55.6% vs 68.4%, P = .491, respectively) even
      with no statistical significance. CONCLUSIONS: The status of IGFBP-3 methylation
      as measured by methylation-specific polymerase chain reaction proposed the modest
      role for predicting survival in specific subgroups of patients with early-stage
      gastric cancer who undergo curative surgery. However, this needs further
      investigation.

PMID- 26310376
TI  - Cyclin-Dependent Kinase 5 (CDK5) Controls Melanoma Cell Motility, Invasiveness,
      and Metastatic Spread-Identification of a Promising Novel therapeutic target.
AB  - Despite considerable progress in recent years, the overall prognosis of
      metastatic malignant melanoma remains poor, and curative therapeutic options are
      lacking. Therefore, better understanding of molecular mechanisms underlying
      melanoma progression and metastasis, as well as identification of novel
      therapeutic targets that allow inhibition of metastatic spread, are urgently
      required. The current study provides evidence for aberrant cyclin-dependent
      kinase 5 (CDK5) activation in primary and metastatic melanoma lesions by
      overexpression of its activator protein CDK5R1/p35. Moreover, using melanoma in
      vitro model systems, shRNA-mediated inducible knockdown of CDK5 was found to
      cause marked inhibition of cell motility, invasiveness, and anchorage-independent
      growth, while at the same time net cell growth was not affected. In vivo, CDK5
      knockdown inhibited growth of orthotopic xenografts as well as formation of lung
      and liver colonies in xenogenic injection models mimicking systemic metastases.
      Inhibition of lung metastasis was further validated in a syngenic murine melanoma
      model. CDK5 knockdown was accompanied by dephosphorylation and overexpression of
      caldesmon, and concomitant caldesmon knockdown rescued cell motility and
      proinvasive phenotype. Finally, it was found that pharmacological inhibition of
      CDK5 activity by means of roscovitine as well as by a novel small molecule CDK5
      inhibitor, N-(5-isopropylthiazol-2-yl)-3-phenylpropanamide, similarly caused
      marked inhibition of invasion/migration, colony formation, and anchorage
      independent growth of melanoma cells. Thus, experimental data presented here
      provide strong evidence for a crucial role of aberrantly activated CDK5 in
      melanoma progression and metastasis and establish CDK5 as promising target for
      therapeutic intervention. 

PMID- 26310377
TI  - Preparation, In Vivo Administration, Dose-Limiting Toxicities, and Antineoplastic
      Activity of Cytochalasin B.
AB  - An effective and inexpensive protocol for producing cytochalasins A and B is
      being disclosed to propose a viable method by which to examine the in vivo
      antineoplastic activity of these congeners in preclinical tumor-bearing mammalian
      models. In addition, we determine the maximum tolerated doses of cytochalasin B
      using multiple routes and formulations, characterize the tissue distribution of
      intravenous bolus cytochalasin B, and assess the in vivo antineoplastic activity
      of cytochalasin B in comparison in doxorubicin in Balb/c mice challenged
      intradermally with M109 murine lung carcinoma. We also examine the effects of
      cytochalasin B against several other murine neoplastic cell lines (Lewis lung,
      LA4, B16F10, and M5076). Finally, we examine a potential mechanism of the
      antimetastatic activity of cytochalasin B by observing the effects of the agent
      on the secretion of N-acetylglucosaminidase (GlcNACase) by B16BL6 and B16F10
      murine melanomas in vitro. The results of the study can be summarized as follows:
      1) Cytochalasin B can be safely administered intravenously, intraperitoneally,
      and subcutaneously in murine models, with the maximum tolerated dose of all
      routes of administration being increased by liposome encapsulation. 2)
      Cytochalasin B can significantly inhibit the growth of tumors in mice challenged
      with M109, Lewis lung, LA4, B16F10, or M5076, producing long-term survival
      against lung carcinomas and adenocarcinomas (M109, Lewis lung, and LA4) and
      B16F10 melanoma, but not M5076 sarcoma. These effects were comparable to
      intraperitoneally administered doxorubicin. 4) Low concentrations of cytochalasin
      B inhibit the secretion of GlcNACase, indicating that cytochalasin B may inhibit
      metastatic progression by mechanisms not directly associated with its influence
      on cell adhesion and motility. 

PMID- 26310378
TI  - Characterization and Clinical Implication of Th1/Th2/Th17 Cytokines Produced from
      Three-Dimensionally Cultured Tumor Tissues Resected from Breast Cancer Patients.
AB  - OBJECTIVES: Several cytokines secreted from breast cancer tissues are suggested
      to be related to disease prognosis. We examined Th1/Th2/Th17 cytokines produced
      from three-dimensionally cultured breast cancer tissues and related them with
      patient clinical profiles. METHODS: 21 tumor tissues and 9 normal tissues
      surgically resected from breast cancer patients were cultured in thermoreversible
      gelatin polymer-containing medium. Tissue growth and Th1/Th2/Th17 cytokine
      concentrations in the culture medium were analyzed and were related with hormone
      receptor expressions and patient clinical profiles. RESULTS: IL-6 and IL-10 were
      expressed highly in culture medium of both cancer and normal tissues. However,
      IFN-gamma, TNF-alpha, IL-2, and IL-17A were not detected in the supernatant of
      the three-dimensionally cultured normal mammary gland and are seemed to be
      specific to breast cancer tissues. The growth abilities of hormone receptor
      negative cancer tissues were significantly higher than those of receptor-positive
      tissues (P=0.0383). Cancer tissues of stage >=IIB patients expressed
      significantly higher TNF-alpha levels as compared with those of patients with
      stage <IIB (P=0.0096). CONCLUSIONS: The tumor tissues resected from breast cancer
      patients can grow in the three-dimensional thermoreversible gelatin polymer
      culture system and produce Th1/Th2/Th17 cytokines. Hormone receptor-positive
      cancer tissues showed less growth ability. TNF-alpha is suggested to be a
      biomarker for the cancer stage.

PMID- 26310379
TI  - Enhancement of the Immunostimulatory Functions of Ex Vivo-Generated Dendritic
      Cells from Early-Stage Colon Cancer Patients by Consecutive Exposure to Low Doses
      of Sequential-Kinetic-Activated IL-4 and IL-12. A Preliminary Study.
AB  - Dendritic cells (DCs), specialized antigen-presenting cells bridging innate and
      adaptive immunity, play a crucial role in determining specific immune response to
      tumors. Because of their potent immunoregulatory capacities, DCs have been
      exploited in anticancer vaccination, with limited success thus far. This pilot
      study compared low-dose interleukin (IL)-4 and IL-12 prepared by sequential
      kinetic activation (SKA) with standard doses of the same recombinant human
      cytokines on functional activity of ex vivo-generated monocyte-derived (Mo) DCs
      from colon carcinoma patients and normal subjects. MoDCs were exposed to medium
      alone, SKA-IL-4 (0.5 fg/ml), or SKA-IL-12 (2 fg/ml), alone or consecutively
      combined, in parallel with rhIL-4 (50 ng/ml) and rhIL-12 (1 ng/ml). Primary
      allogeneic one-way mixed lymphocyte reaction (MLR) was the end point to assess in
      vitro T-lymphocyte proliferation in response to MoDCs, and secreted IL-12p70 and
      interferon-gamma in MLR supernatants measured by ELISA to assay for T-helper 1
      promoting MoDC phenotype. No single agent enhanced the compromised
      allostimulatory activity of MoDCs from colon cancer patients, unlike healthy
      donors. However, MoDCs from nonmetastatic colon cancer patients, after sequential
      exposure to SKA-IL-4 (48 hours) and SKA-IL-12 (24 hours), displayed increased T
      cell stimulatory capacity by MLR and acquired driving T-helper 1 polarization
      activity, although less markedly than the effects induced by recombinant human
      cytokines or found in normal subjects. These results point to an immunomodulatory
      capacity of low-dose SKA-IL-4 and SKA-IL-12 and encourage further investigation
      to provide clues for the rational development of new and more effective
      immunotherapeutic strategies against cancer. 

PMID- 26310380
TI  - Preoperative C-Reactive Protein/Albumin Ratio Predicts Prognosis of Patients
      after Curative Resection for Gastric Cancer.
AB  - BACKGROUND: An elevated preoperative C-reactive protein/albumin (CRP/Alb) ratio
      has been reported to be associated with a poor prognosis for hepatocellular
      carcinoma. The aim of the present study was to investigate the prognostic value
      of the preoperative CRP/Alb ratio and compare it with other systemic inflammatory
      response markers in patients with gastric cancer (GC). METHODS: A retrospective
      study was performed in 455 patients with GC undergoing curative resection. We
      investigated the correlations between the preoperative CRP/Alb ratio and overall
      survival (OS). Kaplan-Meier and Cox regression models were used to assess
      independent prognostic factors. The area under the curve was used to compare the
      prognostic value of different markers. RESULTS: On multivariate analysis, the
      CRP/Alb ratio were independently associated with OS in patients with GC (hazard
      ratio: 1.626; 95% confidence interval: 1.191-2.219; P = .002), along with age (P
      = .003), preoperative body weight loss (P = .001), tumor location (P = .008),
      metastatic lymph node ratio (P < .001), and seventh tumor-nodes-metastasis stage
      (American Joint Committee on Cancer) (P = .007). However, several other systemic
      inflammation-based prognostic scores (neutrophil lymphocyte ratio, platelet
      lymphocyte ratio and systemic immune-inflammation index, Glasgow Prognostic
      Score, modified Glasgow prognostic score, and high-sensitivity modified Glasgow
      prognostic score) were not. In addition, the CRP/Alb ratio had a higher area
      under the curve value (0.625) compared with several other systemic inflammation
      based prognostic scores (P < .001). CONCLUSION: The preoperative CRP/Alb ratio, a
      system inflammation-based prognostic score, is a superior predictor of OS in
      patients undergoing curative resection for GC and may help to identify the high
      risk patients for treatment decisions.

PMID- 26310381
TI  - Impaired neural reward processing in children and adolescents with reactive
      attachment disorder: A pilot study.
AB  - Reactive attachment disorder (RAD) is characterized by markedly disturbed and
      developmentally inappropriate social relatedness due to parental maltreatment.
      RAD patients often display a high number of comorbid attention
      deficit/hyperactivity disorder (ADHD) symptoms, and certain RAD symptoms are
      difficult to discriminate from ADHD. One of the core characteristics of ADHD is a
      decrease in neural reward processing due to dopamine dysfunction. The aim of the
      present study was to determine whether the brain activity involved in reward
      processing in RAD patients is impaired in comparison with ADHD patients and
      typically developed controls. Five RAD patients, 17 typically developed (TD)
      controls and 17 ADHD patients aged 10-16 years performed tasks with high and low
      monetary reward while undergoing functional magnetic resonance imaging. ADHD
      patients were tested before and after 3 months treatment with osmotic release
      oral system-methylphenidate. Before treatment, ADHD patients showed that striatal
      and thalamus activities only in the tasks with low monetary reward were lower
      than TD controls. RAD patients showed decrease in activity of the caudate,
      putamen and thalamus during both the high and low monetary reward conditions in
      comparison with all the other groups. In RAD patients, the activity of the
      putamen was associated with the severity of posttraumatic stress and overt
      dissociation. Reward sensitivity was markedly decreased in children and
      adolescents with RAD, as evidenced by a diminished neural response during reward
      perception. This suggests that dopaminergic dysfunction exists in these patients,
      and may inform future dopaminergic treatment strategies for RAD. 

PMID- 26310382
TI  - Toxicological evaluation of ametryn effects in Wistar rats.
AB  - Sao Paulo state, Brazil, is one of the main areas of sugar cane planting in the
      world. Extensive use of ametryn, a triazine herbicide, in sugar cane agriculture
      and the properties of this herbicide suggest it could be present in the
      environment as a potential contaminant of soil, surface water, groundwater, and
      river sediment. In order to clarify the mechanism through which ametryn could be
      toxic, an in vivo study with Wistar rats was conducted using hematological,
      biochemical, molecular, morphological and genotoxic approaches. For this purpose,
      two sub-lethal ametryn concentrations (15 mg and 30 mg/kg/day) were administered
      to 42 rats divided into three groups (n=12) by gavage during 56 days, whereupon
      blood, liver and bone marrow were collected. The results showed ametryn genotoxic
      activity by in vivo micronuclei testing. This event probably occurred as
      consequence of oxidative stress induction demonstrated by GSTM1 transcript levels
      increase (indicating complexation between ametryn and/or metabolites with GSH)
      and by SOD activity decrease. Also, Mn-SOD transcripts were increased, probably
      avoiding mtDNA damage caused by EROS. These mechanisms displayed hepatic stellate
      cell (HSCs) activation because two major biomarkers were regulated, connexin and
      cadherin. N-cad transcripts were increased on both exposed groups while E-cad
      decreased in the T1 group, indicating epithelial-to-mesenchymal transition. In
      addition, Cx43 transcripts were decreased suggesting an increase in collagen
      content. Volumetric proportion of sinusoids was significantly decreased in T1
      group and no significant alteration in hepatocyte volume was observed, indicating
      an increase in the space of Disse, due to fibrosis. Hepatocyte nuclei showed
      significant decrease in diameter and volume. Few hematological alterations were
      found. We emphasize the importance of other approaches, such as cell death and
      proliferation assays, so that ametryn toxicity can better be understood.

PMID- 26310383
TI  - Slow recovery of tropical old-field rainforest regrowth and the value and
      limitations of active restoration.
AB  - There is current debate about the potential for secondary regrowth to rescue
      tropical forests from an otherwise inevitable cascade of biodiversity loss due to
      land clearing and scant evidence to test how well active restoration may
      accelerate recovery. We used site chronosequences to compare developmental
      trajectories of vegetation between self-organized (i.e., spontaneous) forest
      regrowth and biodiversity plantings (established for ecological restoration, with
      many locally native tree species at high density) in the Australian wet tropics
      uplands. Across 28 regrowth sites aged 1-59 years, some structural attributes
      reached reference rainforest levels within 40 years, whereas wood volume and most
      tested components of native plant species richness (classified by species'
      origins, family, and ecological functions) reached less than 50% of reference
      rainforest values. Development of native tree and shrub richness was particularly
      slow among species that were wind dispersed or animal dispersed with large (>10
      mm) seeds. Many species with animal-dispersed seeds were from near-basal
      evolutionary lineages that contribute to recognized World Heritage values of the
      study region. Faster recovery was recorded in 25 biodiversity plantings of 1-25
      years in which wood volume developed more rapidly; native woody plant species
      richness reached values similar to reference rainforest and was better
      represented across all dispersal modes; and species from near-basal plant
      families were better (although incompletely) represented. Plantings and regrowth
      showed slow recovery in species richness of vines and epiphytes and in overall
      resemblance to forest in species composition. Our results can inform decision
      making about when and where to invest in active restoration and provide strong
      evidence that protecting old-growth forest is crucially important for sustaining
      tropical biodiversity. 

PMID- 26310384
TI  - Alkaline flocculation of Phaeodactylum tricornutum induced by brucite and
      calcite.
AB  - Alkaline flocculation holds great potential as a low-cost harvesting method for
      marine microalgae biomass production. Alkaline flocculation is induced by an
      increase in pH and is related to precipitation of calcium and magnesium salts. In
      this study, we used the diatom Phaeodactylum tricornutum as model organism to
      study alkaline flocculation of marine microalgae cultured in seawater medium.
      Flocculation started when pH was increased to 10 and flocculation efficiency
      reached 90% when pH was 10.5, which was consistent with precipitation modeling
      for brucite or Mg(OH)2. Compared to freshwater species, more magnesium is needed
      to achieve flocculation (>7.5mM). Zeta potential measurements suggest that
      brucite precipitation caused flocculation by charge neutralization. When calcium
      concentration was 12.5mM, flocculation was also observed at a pH of 10. Zeta
      potential remained negative up to pH 11.5, suggesting that precipitated calcite
      caused flocculation by a sweeping coagulation mechanism.

PMID- 26310385
TI  - Successful radiotherapy for repeated recurrent uterine clear cell adenocarcinoma.
AB  - Uterine clear cell adenocarcinoma (UCCA) is rare and resistant to treatment. We
      report a UCCA patient who responded to radiotherapy on each relapse. The first
      relapse was detected in the vaginal wall after the first course of postoperative
      adjuvant chemotherapy. Radiotherapy was conducted. Recurrent tumors were detected
      in the left lung after 5 months and in the right lung after 8 months. Partial
      resection of the lungs was performed. After 5 months, relapse was detected in the
      left pulmonary apex. Stereotactic radiotherapy was conducted. After 7 months,
      relapse was detected in the left pulmonary apex outside the irradiation field,
      and stereotactic radiotherapy was performed. During the subsequent 36-month
      follow-up, there has been no relapse. Although UCCA is resistant to treatment,
      radiotherapy is effective in some cases, as demonstrated in this patient. Even
      when relapse is repeated, radiotherapy may be considered as a treatment option if
      the recurrent focus is localized. 

PMID- 26310386
TI  - Stop and look! Evidence for a bias towards virtual navigation response strategies
      in children with ADHD symptoms.
AB  - Studies in children show that the development of spatial competence emerges
      between seven and eight years of age. Multiple memory systems (hippocampus
      dependent spatial and caudate nucleus-dependent response learning) are involved
      in parallel processing of information during navigation. As a hippocampus
      dependent spatial strategy also relies on frontoparietal executive control and
      working memory networks that are impaired in ADHD, we predicted that children
      will be more likely to adopt a response strategy as they exhibit ADHD symptoms.
      We tested 285 healthy children on a virtual radial-arm maze paradigm in order to
      test this hypothesis. We found that children displaying at least one ADHD symptom
      were more likely to have a perfect performance on a probe trial, which suggests
      that they did not rely on environmental landmarks. Children with ADHD symptoms
      may primarily rely on caudate nucleus-dependent response learning strategies at
      the expense of hippocampus-dependent spatial strategies. Repetition and reward
      based learning strategies, which are hallmarks of response learning, may be most
      effective in children exhibiting ADHD symptoms. 

PMID- 26310387
TI  - Lumbar paraspinal muscle transverse area and symmetry in dogs with and without
      degenerative lumbosacral stenosis.
AB  - OBJECTIVES: To investigate whether dogs with degenerative lumbosacral stenosis
      have decreased lumbar paraspinal muscle transverse area and symmetry compared
      with control dogs. MATERIALS AND METHODS: Retrospective cross-sectional study
      comparing muscles in transverse T2-weighted magnetic resonance images for nine
      dogs with and nine dogs without degenerative -lumbosacral stenosis. Mean
      transverse area was measured for the lumbar multifidus and sacrocaudalis dorsalis
      lateralis muscles bilaterally and the L7 vertebral body at the level of the
      caudal endplate. Transverse areas of both muscle groups relative to L7 and
      asymmetry indices were compared between study populations using independent t
      tests. RESULTS: Mean muscle-to-L7 transverse area ratios were significantly
      smaller in the degenerative lumbosacral stenosis group compared with those in the
      control group in both lumbar multifidus (0.84 +/-0.26 versus 1.09 +/-0.25;
      P=0.027) and sacrocaudalis dorsalis lateralis (0.5 +/-0.15 versus 0.68 +/-0.12;
      P=0.005) muscles. Mean asymmetry indices were higher for both muscles in the
      group with degenerative lumbosacral stenosis than in the control group, but
      highly variable and the difference was not statistically significant. CLINICAL
      SIGNIFICANCE: These findings suggest that dogs with degenerative lumbosacral
      stenosis have decreased lumbar paraspinal muscle mass that may be a cause or
      consequence of the -syndrome. Understanding altered paraspinal muscle
      characteristics may improve understanding of the -pathophysiology and management
      options for degenerative lumbosacral stenosis.

PMID- 26310388
TI  - Improving the efficiency of estimation in the additive hazards model for
      stratified case-cohort design with multiple diseases.
AB  - The case-cohort study design has often been used in studies of a rare disease or
      for a common disease with some biospecimens needing to be preserved for future
      studies. A case-cohort study design consists of a random sample, called the
      subcohort, and all or a portion of the subjects with the disease of interest. One
      advantage of the case-cohort design is that the same subcohort can be used for
      studying multiple diseases. Stratified random sampling is often used for the
      subcohort. Additive hazards models are often preferred in studies where the risk
      difference, instead of relative risk, is of main interest. Existing methods do
      not use the available covariate information fully. We propose a more efficient
      estimator by making full use of available covariate information for the additive
      hazards model with data from a stratified case-cohort design with rare (the
      traditional situation) and non-rare (the generalized situation) diseases. We
      propose an estimating equation approach with a new weight function. The proposed
      estimators are shown to be consistent and asymptotically normally distributed.
      Simulation studies show that the proposed method using all available information
      leads to efficiency gain and stratification of the subcohort improves efficiency
      when the strata are highly correlated with the covariates. Our proposed method is
      applied to data from the Atherosclerosis Risk in Communities study.

PMID- 26310389
TI  - Impact of leadership styles adopted by head nurses on job satisfaction: a
      comparative study between governmental and private hospitals in Jordan.
AB  - BACKGROUND: Previous studies demonstrated that leadership styles are the basis of
      daily interactions between leaders and employees and facilitate and enhance work
      processes. AIM: This study aimed to explore how the leadership styles of nurse
      leaders affect job satisfaction among working nurses. METHODS: Quantitative,
      descriptive and comparative methods were used. Three main Ministry of Health
      hospitals in different areas of Jordan and three private hospitals in Amman were
      selected. RESULTS: Among the leadership styles measured by the Multi-factor
      Leadership Questionnaire 5X, transformational leadership had been used by head
      nurse managers in both settings more than transactional leadership and passive
      avoidant leadership. The level of job satisfaction among nursing staff was higher
      in public hospitals than in private hospitals in this study. A positive
      relationship was found between the overall score for transformational leadership
      and job satisfaction (r = 0.374**). The overall transactional leadership score
      correlated positively with job satisfaction (r = 0.391**). Conversely, the
      overall correlation between passive-avoidant leadership and job satisfaction was
      negative (r = -0.240). CONCLUSION: The increased development of transformational
      leadership behaviours increases nurses' job satisfaction and thus contributes to
      an increased retention of nurses. IMPLICATIONS FOR NURSING MANAGEMENT: The
      ability of hospitals to address the leadership styles of head nurses and their
      impacts on job satisfaction will be strengthened.

PMID- 26310390
TI  - Posterior vs. anterior circulation infarction: demography, outcomes, and
      frequency of hemorrhage after thrombolysis.
AB  - BACKGROUND: Intravenous thrombolysis is considered to be the standard specific
      reperfusion therapy in acute ischemic stroke in both anterior and posterior
      cerebral circulation. AIMS: Our aim was to evaluate the 90-day outcome and rate
      of intracranial hemorrhage after recombinant tissue plasminogen activator
      administration in posterior circulation stroke and to compare the intracranial
      hemorrhage risk for posterior circulation stroke and anterior circulation stroke.
      METHODS: The set consisted of 877 consecutive acute ischemic stroke patients (777
      anterior circulation stroke; 100 posterior circulation stroke) who underwent
      intravenous thrombolysis with recombinant tissue plasminogen activator in a
      standard dose of 0.9 mg/kg. The role of following factors was assessed:
      presenting characteristics, intracranial hemorrhage classification according to
      ECASS I, mortality, and 90-day clinical outcome assessed using the modified
      Rankin scale. RESULTS: Good clinical outcomes (modified Rankin scale 0-2) were
      noted in 59% of posterior circulation stroke patients, with a mortality rate of
      19%. Intracerebral hemorrhage was significantly less frequent in posterior
      circulation stroke than in anterior circulation stroke patients (5.1 vs. 17.2%; P
      = 0.002). The risk of large hemorrhage (parenchymal hematoma 1 and 2) was 5.2
      times higher in anterior circulation stroke patients (P = 0.007). The following
      additional statistically significant differences were found between posterior
      circulation stroke and anterior circulation stroke patients: median age, male
      gender, presence of atrial fibrillation, hyperlipidemia, median time to
      treatment, and median blood glucose level on admission. CONCLUSIONS: Our study
      suggests that posterior circulation stroke is associated with a lower risk of
      intracranial hemorrhage than anterior circulation stroke is.

PMID- 26310391
TI  - MiR-124 exerts tumor suppressive functions on the cell proliferation, motility
      and angiogenesis of bladder cancer by fine-tuning UHRF1.
AB  - UHRF1, an epigenetic factor, is implicated in various cellular processes of
      tumorigenesis. However, the modulation of UHRF1 expression in human bladder
      cancer at post-transcriptional levels remains unclear. Here, we report that miR
      124 suppresses expression of UHRF1 to affect the progression of human bladder
      cancer through competitive binding of the same region of its 3'-UTR. We show that
      compared with corresponding normal tissues, UHRF1 is upregulated and miR-124 is
      downregulated in bladder cancer tissues, demonstrating an inverse correlation of
      miR-124 and UHRF1. Quantitative PCR and western blot assay demonstrated that over
      expression of miR-124 resulted in the suppression of UHRF1. Furthermore,
      luciferase assay revealed that miR-124 could control the fate of target gene
      UHRF1 mRNA by binding 3'-UTR. The rescue experiment confirmed that miR-124
      exerted its biological functions by targeting UHRF1. miR-124 over-expression
      significantly attenuated cellular proliferation, migration, invasion and
      vasculogenic mimicry in vitro, and tumor growth in vivo. UHRF1 siRNA showed
      significant inhibitory effects on bladder cancer cells. Collectively, our study
      demonstrates that miR-124 can impair the proliferation or metastasis of human
      bladder cancer cells by down-regulation of UHRF1. 

PMID- 26310392
TI  - Effects of Attention Deficit Hyperactivity Disorder and Stimulant Medication on
      Concussion Symptom Reporting and Computerized Neurocognitive Test Performance.
AB  - Effects of attention deficit hyperactivity disorder (ADHD) and stimulant
      medications on concussion measures are unclear. The objectives of this study were
      to (i) examine consistency of performance in an unmedicated ADHD group and a
      control group on concussion measures, (ii) assess performance differences between
      the two groups, and (iii) assess the effect of stimulant medication on
      performance in the ADHD group. College-aged participants (22 ADHD and 22 matched
      controls) were administered a symptom checklist and a computerized neurocognitive
      test (CNS Vital Signs, CNSVS) 3 times (1 week apart): Sessions 1 and 2 were
      unmedicated for all participants; Session 3 was medicated for the ADHD group. The
      reliability of the measures (intraclass correlation coefficients, ICC2,1) was
      consistent for both groups. When unmedicated, the ADHD group performed worse than
      controls on psychomotor speed [F(1,40) = 15.19, p < 0.001], and worse than when
      medicated on reaction time [F(1,39) = 6.34, p = 0.02]. The ADHD group performed
      better and comparable with controls when medicated. Clinicians should take
      medication status into account when interpreting scores.

PMID- 26310393
TI  - A Comparison of the Stability and Reactivity of Diamido- and Diaminocarbene
      Copper Alkoxide and Hydride Complexes.
AB  - The mononuclear N-heterocyclic carbene (NHC) copper alkoxide complexes [(6
      NHC)CuOtBu] (6-NHC = 6-MesDAC (1), 6-Mes (2)) have been prepared by addition of
      the free carbenes to the tetrameric tert-butoxide precursor [Cu(OtBu)]4, or by
      protonolysis of [(6-NHC)CuMes] (6-NHC = 6-MesDAC (3), 6-Mes (4)) with tBuOH. In
      contrast to the relatively stable diaminocarbene complex 2, the diamidocarbene
      derivative 1 proved susceptible to both thermal and hydrolytic ring-opening
      reactions, the latter affording [(6-MesDAC)Cu(OC(O)CMe2C(O)N(H)Mes)(CNMes)] (6).
      The intermediacy of [(6-MesDAC)Cu(OH)] in this reaction was supported by the
      generation of Cu2O as an additional product. Attempts to generate an isolable
      copper hydride complex of the type [(6-MesDAC)CuH] by reaction of 1 with Et3SiH
      resulted instead in migratory insertion to generate [(6-MesDAC-H)Cu(P(p-tolyl)3)]
      (9) upon trapping by P(p-tolyl)3. Migratory insertion was also observed during
      attempts to prepare [(6-Mes)CuH], with [(6-Mes-H)Cu(6-Mes)] (10) isolated,
      following a reaction that was significantly slower than in the 6-MesDAC case. The
      longer lifetime of [(6-Mes)CuH] allowed it to be trapped stoichiometrically by
      alkyne, and also employed in the catalytic semi-reduction of alkynes and
      hydrosilylation of ketones.

PMID- 26310394
TI  - Chiral cyclopentadienyl iridium(III) complexes promote enantioselective
      cycloisomerizations giving fused cyclopropanes.
AB  - The cyclopentadienyl (Cp) group is a very important ligand for many transition
      metal complexes which have been applied in catalysis. The availability of chiral
      cyclopentadienyl ligands (Cp(x) ) lags behind other ligand classes, thus
      hampering the investigation of enantioselective processes. We report a library of
      chiral Cp(x) Ir(III) complexes equipped with an atropchiral Cp scaffold. A robust
      complexation procedure reliably provides Cp(x) Ir(III) complexes with tunable
      counterions. In a proof-of-concept application, the iodide-bearing members are
      shown to be highly selective for enyne cycloisomerization reactions. The
      dehydropiperidine-fused cyclopropane products are formed in good yields and
      enantioselectivities. 

PMID- 26310395
TI  - A prediction model to estimate completeness of electronic physician claims
      databases.
AB  - OBJECTIVES: Electronic physician claims databases are widely used for chronic
      disease research and surveillance, but quality of the data may vary with a number
      of physician characteristics, including payment method. The objectives were to
      develop a prediction model for the number of prevalent diabetes cases in fee-for
      service (FFS) electronic physician claims databases and apply it to estimate
      cases among non-FFS (NFFS) physicians, for whom claims data are often incomplete.
      DESIGN: A retrospective observational cohort design was adopted. SETTING: Data
      from the Canadian province of Newfoundland and Labrador were used to construct
      the prediction model and data from the province of Manitoba were used to
      externally validate the model. PARTICIPANTS: A cohort of diagnosed diabetes cases
      was ascertained from physician claims, insured resident registry and
      hospitalisation records. A cohort of FFS physicians who were responsible for the
      diagnosis was ascertained from physician claims and registry data. PRIMARY AND
      SECONDARY OUTCOME MEASURES: A generalised linear model with a gamma distribution
      was used to model the number of diabetes cases per FFS physician as a function of
      physician characteristics. The expected number of diabetes cases per NFFS
      physician was estimated. RESULTS: The diabetes case cohort consisted of 31,714
      individuals; the mean cases per FFS physician was 75.5 (median = 49.0). Sex and
      years since specialty licensure were significantly associated (p < 0.05) with the
      number of cases per physician. Applying the prediction model to NFFS physician
      registry data resulted in an estimate of 18,546 cases; only 411 were observed in
      claims data. The model demonstrated face validity in an independent data set.
      CONCLUSIONS: Comparing observed and predicted disease cases is a useful and
      generalisable approach to assess the quality of electronic databases for
      population-based research and surveillance.

PMID- 26310396
TI  - Examining the role of Scotland's telephone advice service (NHS 24) for managing
      health in the community: analysis of routinely collected NHS 24 data.
AB  - OBJECTIVES: To examine the type, duration and outcome of the symptoms and health
      problems Scotland's nurse-led telephone advice service (NHS 24) is contacted
      about and explore whether these vary by time of contact and patient
      characteristics. DESIGN: Analysis of routinely collected NHS 24 data. SETTING:
      Scotland, UK. PARTICIPANTS: Users of NHS 24 during 2011. MAIN OUTCOME MEASURES:
      Proportion of the type, duration and outcome of the symptoms and health problems
      NHS 24 is contacted about. RESULTS: 82.6% of the calls were made out-of-hours and
      17.4% in-hours. Abdominal problems accounted for the largest proportion of calls
      (12.2%) followed by dental (6.8%) and rash/skin problems (6.0%). There were
      differences in the type of problems presented in-hours and out-of-hours. Most
      problems (62.9%) had lasted <24 h before people contacted NHS 24. Out-of-hours
      calls tended to be for problems of shorter duration. Problems reported out-of
      hours most commonly resulted in advice to visit an out-of-hours centre and in
      hours advice to contact a general practitioner. Most of the service users were
      female and from more affluent areas. Use of the service declined with age in
      those over 35 years. The characteristics of users varied according to when NHS 24
      was contacted. The number of calls made by an individual in the year ranged from
      1 to 866, although most users (69.2%) made only one call. The type of problem
      presented varied by age and deprivation, but was broadly similar by gender,
      rural/urban status and geographic area. Call outcomes also varied by user
      characteristics. CONCLUSIONS: This is the first study to examine how the public
      uses NHS 24. It has identified the patterns of problems which the service must be
      equipped to deal with. It has also provided important information about who uses
      the service and when. This information will help future planning and development
      of the service.

PMID- 26310397
TI  - Changes in cardiovascular health score and atherosclerosis progression in middle
      aged and older persons in China: a cohort study.
AB  - OBJECTIVES: The American Heart Association (AHA) proposed a definition of 4
      cardiovascular health behaviours and 3 health factors. On the basis of the 7
      metrics, the cardiovascular health score (CHS) was used to estimate individual
      level changes in cardiovascular health status. The aim of this study was to
      investigate whether changes in CHS (?CHS) at different time-points are associated
      with atherosclerosis progression in middle-aged and older persons. DESIGN:
      Prospective cohort study in China. SETTINGS: We defined 8 groups (<=-4, -3, -2, 
      1, 0, 1, 2 and >= 3) according to ?CHS. The impact of ?CHS on the change of
      brachial-ankle pulse wave velocity (?baPWV) and atherosclerosis progression was
      analysed. PARTICIPANTS: A total of 3951 individuals met the inclusion criteria
      (>= 40 years old; no history of stroke, transient ischaemic attack or myocardial
      infarction) and had complete information. RESULTS: ?baPWV decreased gradually
      (126.46 +/- 355.91, 78.4 +/- 343.81, 69.6 +/- 316.27, 49.59 +/- 287.57, 57.07 +/-
      261.17, 40.45 +/- 264.27, 37.45 +/- 283.26 and 21.66 +/- 264.17 cm/s,
      respectively) with increasing ?CHS (p for trend<0.05). Multivariate linear
      regression analysis suggested a negative relationship between these 2 variables,
      which persisted after adjustment for other risk factors. Each increase in CHS was
      associated with a reduced baPWV for 15.22 cm/s (B value -15.22, p<0.001).
      CONCLUSIONS: ?CHS were negatively related to ?baPWV, which proved to be an
      independent predictor of the progression of atherosclerosis in middle-aged and
      older persons. TRIAL REGISTRATION NUMBER: Kailuan study (ChiCTR-TNC-11001489).

PMID- 26310399
TI  - Conflict-of-interest disclosure at medical journals in Japan: a nationwide survey
      of the practices of journal secretariats.
AB  - OBJECTIVES: Medical journals in Japan generally have appropriate policies
      regarding disclosure of conflicts of interest (COI). However, COI management
      depends on the staff members of each journal's editorial secretariat. This
      study's objectives were to find out (A) whether COI disclosure and the journal's
      role in it are clearly understood by the journal's secretariat staff, (B) how
      much experience the editorial secretariat has in actually handling issues related
      to disclosure and (C) what kind of help or support they need. SETTING AND DESIGN:
      In January 2014, questionnaires were sent to the editorial secretariats of
      journal-publishing societies belonging to the Japanese Association of Medical
      Sciences (JAMS). PARTICIPANTS: The response rate was 100%, and the respondents
      represented 121 journals published by the 118 JAMS member societies (at the time
      of the survey). PRIMARY AND SECONDARY OUTCOME MEASURES: Information was collected
      on the history of COI policies and on how those policies were implemented. At the
      end of the questionnaire, there was an open-ended call for comments. RESULTS:
      Compulsory COI disclosure began between 2010 and 2013 for 60.3% of the journals
      (73/121). Handling of COI issues was not uniform: 17.4% (21/121) of respondents
      do not pursue cases of dubious disclosure, and 47.9% (58/121) do not require COI
      disclosures from editorial board members. Very few of the editorial secretariats
      had clearly-stated consequences for violations of COI-disclosure policy (33/121,
      27.3%), and only 28.9% offered COI education (35/121). Respondents' comments
      indicated that uniform, easily-searchable guidance regarding COI policies and
      implementation would be welcome. CONCLUSIONS: Although commitment is widespread,
      policy implementation is inconsistent and COI experience is lacking. Clear, easy
      to-use guidelines are desired by many societies. The JAMS is to be commended for
      supporting this country-wide investigation; other countries and regions are
      encouraged to perform similar investigations to respond to needs regarding COI
      management.

PMID- 26310398
TI  - Association of worker characteristics and early reimbursement for physical
      therapy, chiropractic and opioid prescriptions with workers' compensation claim
      duration, for cases of acute low back pain: an observational cohort study.
AB  - OBJECTIVE: To assess the association between early reimbursement for
      physiotherapy, chiropractic and opioid prescriptions for acute low back pain
      (LBP) with disability claim duration. DESIGN: Observational cohort study. SETTING
      AND PARTICIPANTS: From a random sample of 6665 claims for acute, uncomplicated
      LBP approved by the Ontario Workplace Safety and Insurance Board (WSIB) in 2005,
      we analysed 1442 who remained on full benefits at 4 weeks after claim approval.
      PRIMARY OUTCOME MEASURE: Our primary outcome was WSIB claim duration. RESULTS: We
      had complete data for all but 3 variables, which had <15% missing data, and we
      included missing data as a category for these factors. Our time-to-event analysis
      was adjusted for demographic, workplace and treatment factors, but not injury
      severity, although we attempted to include a sample with very similar, less
      severe injuries. Regarding significant factors and treatment variables in our
      adjusted analysis, older age (eg, HR for age >= 55 vs <25=0.52; 99% CI 0.36 to
      0.74) and WSIB reimbursement for opioid prescription in the first 4 weeks of a
      claim (HR=0.68; 99% CI 0.53 to 0.88) were associated with longer claim duration.
      Higher predisability income was associated with longer claim duration, but only
      among persistent claims (eg, HR for active claims at 1 year with a predisability
      income >$920 vs <=$480/week=0.34; 99% CI 0.17 to 0.68). Missing data for union
      membership (HR=1.27; 99% CI 1.01 to 1.59), and working for an employer with a
      return-to-work programme were associated with fewer days on claim (HR=1.78; 99%
      CI 1.45 to 2.18). Neither reimbursement for physiotherapy (HR=1.01; 99% CI 0.86
      to 1.19) nor chiropractic care (HR for active claims at 60 days=1.15; 99% CI 0.94
      to 1.41) within the first 4 weeks was associated with claim duration. Our meta
      analysis of 3 studies (n=51,069 workers) confirmed a strong association between
      early opioid use and prolonged claim duration (HR=0.57, 95% CI 0.48 to 0.69; low
      certainty evidence). CONCLUSIONS: Our analysis found that early WSIB
      reimbursement for physiotherapy or chiropractic care, in claimants fully off work
      for more than 4 weeks, was not associated with claim duration, and that early
      reimbursement for opioids predicted prolonged claim duration. Well-designed
      randomised controlled trials are needed to verify our findings and establish
      causality between these variables and claim duration.

PMID- 26310400
TI  - E-cigarette use in Canada: prevalence and patterns of use in a regulated market.
AB  - OBJECTIVE: Canada is among the few countries in which e-cigarettes containing
      nicotine are prohibited. To date, there is little evidence on the prevalence and
      patterns of use of e-cigarettes in markets with product bans. The current study
      examines e-cigarette use among a sample of non-smokers and smokers in Canada.
      DESIGN: Online cross-sectional survey. SETTING: Conducted in October 2013 using a
      commercial panel of Canadians from Global Market Insite, Inc (GMI). PARTICIPANTS:
      In total, 1095 Canadians were included in the analysis: 311 non-smokers aged 16
      24 years (younger non-smokers), 323 smokers aged 16-24 years (younger smokers)
      and 461 smokers 25 years and older (older smokers). PRIMARY AND SECONDARY OUTCOME
      MEASURES: E-cigarette ever and current use, types of products used, and reasons
      for use. RESULTS: Approximately 79% of younger non-smokers, 82% of younger
      smokers and 81% of older smokers were aware of e-cigarettes. Ever trial of e
      cigarettes was reported by 10% of younger non-smokers, 42% of younger smokers and
      27% of older smokers. Moreover, current use of an e-cigarette, which was defined
      as use in the last 30 days, was reported by 0.3% of younger non-smokers, 18% of
      younger smokers and 10% of older smokers. Among those who had ever tried an e
      cigarette, approximately 10% of younger non-smokers, 46% of younger smokers and
      43% of older smokers reported trying an e-cigarette that contained nicotine. The
      most popular e-cigarette flavours were fruit followed by menthol, and the most
      common reason for using e-cigarettes was to help them quit smoking. CONCLUSIONS:
      In the context of previous research, it appears that the prevalence of e
      cigarette trial has increased in Canada. Although a considerable proportion of
      non-smokers have tried e-cigarettes, current use is almost entirely concentrated
      among smokers. Further research should be conducted to monitor e-cigarette use by
      Canadians.

PMID- 26310401
TI  - Environmental tobacco smoke and the risk of eczema symptoms among school children
      in South Africa: a cross-sectional study.
AB  - OBJECTIVE: The aim of this study was to investigate the association between
      eczema ever (EE) and current eczema symptoms (ES) in relation to exposure to
      environmental tobacco smoke (ETS). DESIGN: A cross-sectional study using the
      International Study of Asthma and Allergies in Childhood questionnaire. SETTING:
      16 schools were randomly selected from two neighbourhoods situated in Ekurhuleni
      Metropolitan Municipality, Gauteng Province, South Africa. PARTICIPANTS: From a
      total population of 3764 school children aged 12-14 years, 3468 completed the
      questionnaire (92% response rate). A total of 3424 questionnaires were included
      in the final data analysis. PRIMARY OUTCOME: The prevalence of EE and current ES
      was the primary outcome in this study. RESULTS: Data were analysed using
      Multilevel Logistic Regression Analysis (MLRA). The likelihood of EE was
      increased by exposure to ETS at home (OR 1.30 95% CI 1.01 to 1.67) and at school
      (OR 1.26 95% CI 1.00 to 1.60). The likelihood of EE was lower for males (OR 0.66
      95% CI 0.51 to 0.84). The likelihood of ES was increased by ETS at home (OR 1.93
      95% CI 1.43 to 2.59) and school (1.44 95% CI 1.09 to 1.90). The likelihood of ES
      was again lower for males (OR 0.56 95% CI 0.42 to 0.76). Smoking by mother/female
      guardian increased the likelihood of EE and ES, however, this was not significant
      in the multivariate analysis. CONCLUSIONS: Symptoms of eczema were positively
      associated with exposure to ETS at home and school. The results support the
      hypothesis that ETS is an important factor in understanding the occurrence of
      eczema.

PMID- 26310403
TI  - Fibreoptics in anaesthesia and intensive care.

PMID- 26310404
TI  - Revalidation for anaesthetists: will it be effective, evidence-based and
      practical?

PMID- 26310402
TI  - Laser capture microdissection as a tool to evaluate human papillomavirus
      genotyping and methylation as biomarkers of persistence and progression of anal
      lesions.
AB  - INTRODUCTION: Anal squamous cell carcinoma is preceded by persistent infection
      with high-risk human papillomavirus (HPV) and the cancer precursor, high-grade
      squamous intraepithelial lesion (HSIL). Detection of specific HPV genotypes and
      HPV-related biomarkers may be an option for primary anal screening. However, more
      data on the natural history of HPV-related anal lesions are required. The
      outcomes from this study will enhance our understanding of the clinical and
      biological behaviour of HPV-related anal lesions and inform the development of
      future HPV genotype and/or biomarker screening tests. METHODS AND ANALYSIS: HIV
      negative and HIV-positive men who have sex with men, aged 35 years and over,
      recruited from community-based settings in Sydney, Australia, attend 6 clinic
      visits over 3 years. At the first 5 visits, participants undergo a digital
      anorectal examination, an anal swab for HPV genotyping and anal cytology, and
      high-resolution anoscopy with directed biopsy of any visible abnormalities that
      are suggestive of any abnormality suspicious of SIL. Tissue sections from
      participants diagnosed with histologically confirmed HSIL at the baseline clinic
      visit will undergo laser capture microdissection, HPV detection and genotyping,
      and quantitation of CpG methylation in baseline and follow-up biopsies.
      Histological and cytological findings in combination with HPV genotyping data
      will be used to identify persistent HSIL. HSIL will be stratified as non
      persistent and persistent based on their status at 12 months. The performance of
      HPV genotype and methylation status in predicting disease persistence at 12
      months will be assessed, along with associations with HIV status and other
      covariates such as age. ETHICS AND DISSEMINATION: The St Vincent's Hospital
      Ethics Committee granted ethics approval for the study. Written informed consent
      is obtained from all individuals before any study-specific procedures are
      performed. Findings from this study will be disseminated to participants and the
      community through study newsletters, and through peer-reviewed publications and
      international conferences.

PMID- 26310405
TI  - Goals of therapy: should we ask what our patients really want?

PMID- 26310406
TI  - Cognitive function, quality of life and mental health in survivors of our-of
      hospital cardiac arrest: a review.
AB  - There is growing interest in the long-term outcomes of patients surviving out-of
      hospital cardiac arrest (OHCA). This paper aims to summarise the available
      literature on the long-term cognitive, health-related quality of life (QoL) and
      mental health outcomes of survivors of OHCA. Between 30% and 50% of survivors of
      OHCA experience cognitive deficits for up to several years post-discharge.
      Deficits of attention, declarative memory, executive function, visuospatial
      abilities and verbal fluency are commonly reported. Survivors of OHCA appear to
      report high rates of mental illness, with up to 61% experiencing anxiety, 45%
      experiencing depression and 27% experiencing post-traumatic stress. Fatigue
      appears to be a commonly reported long-term outcome for survivors of OHCA.
      Investigations of long-term QoL for these patients have produced mixed findings.
      Carers of survivors of OHCA report high rates of depression, anxiety and post
      traumatic stress, with insufficient social and financial support. The
      heterogeneous range of instruments used to assess cognitive function and QoL
      prevent any clear conclusions being drawn from the available literature. The
      potential biases inherent in this patient population and the interaction between
      QoL, cognitive performance and mental health warrant further investigation, as
      does the role of post-discharge support services in improving long-term patient
      outcomes. 

PMID- 26310407
TI  - Prospective observational study of emergency airway management in the critical
      care environment of a tertiary hospital in Melbourne.
AB  - The objective of this study is to describe the population of patients receiving
      emergency airway management outside operating theatres at our institution, a
      tertiary referral centre in Melbourne. A registry of all patients receiving
      emergency airway management in the emergency department, ICU and on the wards as
      part of Medical Emergency Response teams' care, was prospectively collected.
      There were 128 adults and one paediatric patient requiring emergency airway
      management recruited to the study. Data for analysis included patient
      demographics, pre-oxygenation and apnoeic oxygenation, staff, drugs, details of
      laryngoscopic attempts, adjuncts, airway manoeuvres, complications sustained and
      method of confirmation of endotracheal tube placement. Over a 12-month period,
      there were 139 intubations of 129 patients, requiring a total of 169 attempts.
      Respiratory failure was the most common indication for intubation. Intubation was
      successful on the first episode of laryngoscopy in 116 (83.5%) patients.
      Complications occurred in 48 patients. In the cohort of patients without
      respiratory failure, nasal cannulae apnoeic oxygenation significantly reduced the
      incidence of hypoxaemia (0 out of 31 [0.0%] versus 10 out of 60 [16.7%], P=0.016;
      absolute risk reduction 16.7%; number needed to treat: 6). Waveform capnography
      was used to confirm endotracheal tube placement in 133 patients and there were
      four episodes of oesophageal intubation, all of which were recognised
      immediately. In the critical care environment of our institution, emergency
      airway management is achieved with a first-attempt success rate that is
      comparable to overseas data. Nasal cannulae apnoeic oxygenation appears to
      significantly reduce the risk of hypoxaemia in patients without respiratory
      failure and the use of waveform capnography eliminates episodes of unrecognised
      oesophageal intubation. 

PMID- 26310408
TI  - Efficacy of an enteral feeding protocol for providing nutritional support after
      paediatric cardiac surgery.
AB  - Enteral nutrition (EN) is considered to be a more appropriate method than
      parenteral feeding for providing nutrition to critically ill children. However,
      children who undergo cardiac surgery are at high risk of postoperative
      gastrointestinal complications during EN. The purpose of this study was to
      demonstrate the safety and efficacy of our EN feeding protocol after paediatric
      cardiac surgery through comparison between a single-centre prospective case
      series and historical cases. Forty-seven children who were admitted to the ICU
      after cardiac surgery were enrolled ('post group'). Data for these children were
      compared with a similar cohort of children who were admitted before the
      implementation of the feeding protocol (n=62; 'pre group'). The incidence of
      complications including vomiting, necrotising enterocolitis and hypoglycaemia;
      the time until the initiation of EN; and the changes in calories provided were
      compared between the groups. The frequency of vomiting was significantly lower in
      the post group than in the pre group (36.2% versus 58.0%, P=0.038), and
      necrotising enterocolitis did not occur in either group. The time until the
      initiation of EN and the total calories provided did not differ significantly;
      however, in the post group the proportion of energy provided by parenteral
      nutrition was significantly smaller (P <0.001), and provided by EN was
      significantly larger (P=0.003), than in the pre group. The frequency of
      hypoglycaemia was similar in both groups. This study showed that our EN protocol
      resulted in adjustments to calories provided via EN versus parenteral nutrition
      after paediatric cardiac surgery, and reduced the frequency of vomiting. 

PMID- 26310409
TI  - Factors associated with vancomycin nephrotoxicity in the critically ill.
AB  - Vancomycin is a glycopeptide antibiotic commonly used in the management of
      methicillin-resistant Staphylococcus aureus infection. The recent increase in
      prevalence of methicillin-resistant Staphylococcus aureus with reduced
      susceptibility to vancomycin has prompted experts to advocate for higher target
      trough serum concentrations. This study aimed to evaluate the potential
      consequences of more aggressive vancomycin therapy, by examining the association
      between higher serum concentrations and acute kidney injury (AKI) in a population
      of critically ill patients. We collected data for all patients who received
      vancomycin over a five-year period and evaluated the prevalence of new-onset AKI
      using the Risk, Injury, Failure, Loss and End-stage (RIFLE) kidney disease
      criteria. One-hundred and fifty-nine patients provided complete data, with 8.8%
      manifesting new onset AKI while receiving vancomycin. The median age was 57 (44
      to 68) years, while the median trough serum concentration was 16 (10 to 19) mg/l.
      Multivariate logistic regression analysis identified mean trough concentration
      (OR=1.174, P=0.024), APACHE II score (OR=1.141, P=0.012) and simultaneous
      aminoglycoside prescription (OR=18.896, P=0.002) as significant predictors of
      AKI. These data suggest higher trough vancomycin serum concentrations are
      associated with greater odds of AKI in the critically ill. 

PMID- 26310410
TI  - Impact of increasing overnight intensive care unit registrar staffing on duration
      of intubation of elective cardiac surgery patients.
AB  - It is unclear whether increases to overnight junior medical staffing levels can
      improve ICU patient outcomes. We conducted a retrospective cohort study before
      and after the introduction of a third overnight ICU registrar at a 24-bed
      metropolitan ICU in February 2012. We hypothesised that this change would be
      associated with decreased intubation time for elective cardiac surgery patients
      and an increase in the proportion of these patients being extubated during the
      overnight period. All elective cardiac surgery patients were included from two
      temporally matched six-month periods (May to October) in 2011 and 2012. The
      primary outcome was median duration of intubation, and the secondary outcome was
      proportion of patients extubated during the 'overnight' period (2200 to 0700). A
      total of 142 and 188 patients were included in the control and intervention
      cohorts, respectively. Median (IQR) intubation time was 8.7 (6.6 to 14.5) hours
      in the control cohort and 8.2 (6.0 to 13.4) hours in the intervention cohort,
      with no significant difference between groups (P=0.40). The proportion of
      elective cardiac surgery patients extubated during the overnight period was
      similar, 54.2% in the control group compared to 50.0% in intervention group
      (P=0.45). In our unit, increasing overnight ICU registrar staffing levels was not
      associated with a significant reduction in duration of intubation for elective
      cardiac surgery patients or a reduction in the proportion of these patients
      extubated overnight. This is likely due to factors other than medical staffing
      levels influencing timing of extubation of these patients. 

PMID- 26310411
TI  - The utility of a Personal Values Report for medical decision-making.
AB  - Our aim was to determine if a patient's Personal Values Report (PVR) has a
      positive impact on a doctor's decisions regarding treatment. We conducted a
      prospective cohort study delivering a short, web-based hypothetical case-centred
      questionnaire to intensive care doctors practising in Australia and New Zealand.
      One hundred and twenty-four intensive care consultants and registrars agreed to
      participate in an online questionnaire in two routine mailings between November
      2013 and February 2014. We evaluated the effect of a PVR on clinical decision
      making in a case-based scenario. In addition, participants rated the utility of
      the PVR on their decision-making process. Participants were presented with a
      difficult scenario in a frail elderly man where death was almost inevitable
      without aggressive support but survival with severe disability was possible with
      significant intervention. Most doctors (52.4%) elected to continue ventilation
      and admit to ICU. After the PVR was made available, only 8.1% of doctors
      continued to choose to admit the patient to the ICU. In all cases where admission
      to the ICU was chosen after seeing the PVR, the admission to the ICU was stated
      to be to permit family to arrive before withdrawing support (an approach which
      was consistent with the values stated in the PVR). One hundred and twenty-one of
      the 124 participants (97.6%) agreed or strongly agreed that the PVR helped them
      get an understanding of the patient's wishes, whereas none of the participants
      (0%) were unsure, disagreed or strongly disagreed with this statement. The
      remaining 2.4% did not answer the question. It is surmised that PVRs pre-written
      by patients are potentially an effective and valuable tool for use in helping
      doctors make decisions regarding patient care. 

PMID- 26310412
TI  - Iron-restricted erythropoiesis and risk of red blood cell transfusion in the
      intensive care unit: a prospective observational study.
AB  - Intravenous (IV) iron can decrease transfusion requirements in selected patients
      with low, normal and moderately elevated ferritin. Whether the syndrome of iron
      restricted erythropoiesis (IRE), diagnosed by iron studies, identifies critically
      ill patients at risk for subsequent red blood cell (RBC) transfusion, and hence,
      provides a simple method to determine response to IV iron therapy, is uncertain.
      We aimed to describe the characteristics of patients with IRE on admission to
      intensive care and determine the optimal variables to identify patients at risk
      of RBC transfusion who may benefit from early administration of IV iron. The
      study included 201 consecutive ICU admissions from a single 23-bed combined
      medical/surgical ICU. The prevalence of IRE on admission to ICU, defined
      according to ferritin <300 ug/l and transferrin saturation <20%, was 26.2% (95%
      CI 19.9 to 32.4). The proportion of patients with IRE subsequently receiving RBC
      transfusion was significantly lower than the proportion of patients without IRE
      receiving RBC transfusion (absolute mean difference 18.9% [95% CI 4.7 to 33.1, P
      <0.001]). IRE was not independently associated with risk of transfusion on
      multivariate analysis, however, a prognostic model with three risk factors (RBC
      transfusion prior to ICU admission, Hb <100 g/l and ICU length of stay >3 days),
      had good discrimination and calibration for predicting transfusion (receiver
      operator curve area under the curve 0.87 [95% CI 0.79 to 0.94, P=0.88], Hosmer
      Lemeshow 6.21; P=0.1). Excluding iron overload and using simple prognostic
      criteria to identify patients at high risk of RBC transfusion may be a preferable
      strategy for identifying critically ill patients who may benefit from IV iron. 

PMID- 26310413
TI  - Fluid administration, vasopressor use and patient outcomes in a group of high
      risk cardiac surgical patients receiving postoperative goal-directed haemodynamic
      therapy: a pilot study.
AB  - The role of goal-directed therapy in high-risk cardiac surgical patients has not
      been determined. This study sought to observe the effect of a postoperative
      standardised haemodynamic protocol (SHP) on the administration of fluid and
      vasoactive drugs after high-risk cardiac surgery. This was an interventional
      pilot study. In 2010 to 2011, the SHP was introduced to the ICU at Wellington
      Regional Hospital, Wellington, New Zealand, for the perioperative management of
      patients undergoing high-risk cardiac surgery. A pulmonary artery catheter was
      inserted in the patients in the study group and fluids and supportive medications
      were provided in the ICU according to a protocol that targeted a cardiac index >=
      2 l/min/m2, mixed venous oxygen saturation >= 60% and a mean arterial pressure of
      65 to 75 mmHg. Data from 40 consecutive high-risk cardiac surgical patients
      assigned to this protocol were compared with a matched cohort of 40 consecutive
      high-risk cardiac surgical patients receiving 'usual care' in 2009. Baseline
      characteristics were similar in the two groups. There was no significant
      difference in the duration of noradrenaline infusion in the SHP cohort compared
      to historical controls (median [IQR] 18.5 hours [31.63] versus 18 hours [18.3];
      P=0.35), despite patients receiving more fluid in their first 12 hours in the ICU
      (mean 4687 ml [SD +/- 2284 ml] versus 1889 ml [SD +/- 1344 ml]; P <0.001). The
      SHP cohort had a higher rate of reintubation (4 in 37 [10.8%] versus 0 in 40
      [0%]; P=0.049). The SHP delivered significantly more fluid, but did not reduce
      the duration of noradrenaline infusion, compared to usual care.

PMID- 26310414
TI  - Central venous-to-arterial carbon dioxide gradient as a marker of occult tissue
      hypoperfusion after major surgery.
AB  - The central venous-arterial carbon dioxide tension gradient ('CO2gap') has been
      shown to correlate with cardiac output and tissue perfusion in septic shock.
      Compared to central venous oxygen saturation (SCVO2), the CO2gap is less
      susceptible to the effect of hyperoxia and may be particularly useful as an
      adjunctive haemodynamic target in the perioperative period. This study
      investigated whether a high CO2gap was associated with an increased systemic
      oxygen extraction (O2ER >0.3) or occult tissue hypoperfusion in 201 patients in
      the immediate postoperative period. The median CO2gap of all patients was 8 mmHg
      (IQR 6 to 9), and a large CO2gap was very common (> 6mmHg in 139 patients [69%],
      95% CI 63 to 75; >5 mmHg in 170 patients [85%], 95% CI 79 to 89). A CO2 gap >5
      mmHg had a higher sensitivity (93%) and negative predictive value (74%) than a
      CO2gap >6 mmHg in excluding occult tissue hypoperfusion. Of the four variables
      that were predictive of an increased O2ER in the multivariate analysis-CO2gap,
      arterial pH, haemoglobin and arterial lactate concentrations-the CO2gap (odds
      ratio 4.41 per mmHg increment, 95% CI 1.7 to 11.2, P=0.002) was most important
      and explained about 34% of the variability in the risk of occult tissue
      hypoperfusion. In conclusion, a normal CO2 gap (<5 mmHg) had a high sensitivity
      and negative predictive value in excluding inadequate systemic oxygen delivery
      and may be useful as an adjunct to other haemodynamic targets in avoiding occult
      tissue hypoperfusion in the perioperative setting when high inspired oxygen
      concentrations are used.

PMID- 26310415
TI  - Infraclavicular axillary vein cannulation using ultrasound in a mechanically
      ventilated general intensive care population.
AB  - Central venous catheter (CVC) insertion is commonly undertaken in the ICU. The
      use of ultrasound (US) to facilitate CVC insertion is standard and is supported
      by guidelines. Because the subclavian vein cannot be insonated where it underlies
      the clavicle, its use as a CVC site is now less common. The axillary vein,
      however, can be seen on US just distal to the subclavian vein and placement of a
      CVC at this site gives a result which is functionally indistinguishable from a
      subclavian CVC. We evaluated placement of US-guided axillary CVCs in mechanically
      ventilated intensive care patients. Data were collected for 125 consecutive US
      guided axillary CVC procedures in ventilated patients in an adult intensive care
      setting. All lines were inserted using real-time US guidance with an out-of-plane
      technique. One hundred and twenty-five procedures occurred in 119 patients.
      Successful line placement was achieved in 117 out of 125 (94%) procedures.
      Complications included four procedures that required repeating due to catheter
      malposition and one arterial puncture. The median number of attempts per
      procedure was one (IQR 1 to 2). Thirty-nine (31%) patients had a body mass index
      of 30 or above, 43 (34%) patients had a coagulopathy and 70 (56%) patients had
      significant ventilator dependence (FiO2 of 0.5 or above, or positive end
      expiratory pressure 10 cmH20 or above). The technique of US-guided axillary CVC
      access can be undertaken successfully in ventilated intensive care patients, even
      in challenging circumstances. Taken together with existing work on the utility
      and safety of this technique, we suggest that it be adopted more widely in the
      intensive care population. 

PMID- 26310416
TI  - Measurement of peak aortic jet velocity in the perioperative period-machine
      variability: implications for assessment of aortic stenosis severity.
AB  - Variation in echocardiography machines and probes are not well described in the
      perioperative period. We aimed to compare the estimation of severity of aortic
      stenosis with transthoracic echocardiography (TTE) using two semi-portable
      ultrasound machines. Experienced cardiac anaesthetists performed a limited
      transthoracic echocardiogram with two different semi-portable ultrasound machines
      in patients with known aortic stenosis. The peak aortic jet velocity with
      continuous-wave Doppler and the time taken to obtain an acceptable envelope were
      recorded. The Sonosite M Turbo often underestimated the peak jet velocities
      (median jet velocity [IQR] 2.25 m/s [1.95 to 3.4] versus 3.85 m/s (3 to 4.2); P
      <0.001) and required more time to get a satisfactory envelope than the GE Vivid
      I. There was no statistically or clinically significant difference between the
      velocities obtained from the Vivid I and those measured on the patient's formal
      cardiology preoperative transthoracic echocardiogram (median [IQR]: 3.95 m/s [3.0
      to 4.7]; P=0.3). However, the velocities obtained by the M Turbo were
      significantly lower than those obtained by the formal preoperative transthoracic
      echocardiogram (P <0.001). With the expansion of transthoracic echocardiography
      amongst anaesthetists, underestimation of the peak aortic jet velocity can
      significantly underestimate the severity of aortic stenosis with potentially
      lethal clinical consequences. Semi-portable ultrasound machines with
      echocardiographic capability are not necessarily equivalent and can result in
      underestimation of severity of aortic stenosis. 

PMID- 26310417
TI  - Anti-seizure prophylaxis in critically ill patients with traumatic brain injury
      in an intensive care unit.
AB  - The objectives of this prospective observational study were to determine the
      proportion of patients with traumatic brain injury who received effective anti
      seizure prophylaxis. The study was conducted in a tertiary level ICU of a major
      trauma referral centre between February 2012 and August 2013. A total of 2361
      patients were admitted to the ICU in this study period, of whom125 patients
      (index) with traumatic head injury were included in this study. The patients had
      a mean age of 45 years (SD=19), a mean score on the Glasgow Coma Scale of 9
      (SD=4), a mean injury severity score of 27 (SD=13) and a mean APACHE III score of
      55 (SD=27). Only 13.6 % (17 of 125) of patients were given anti-seizure
      prophylaxis and phenytoin levels were measured in 9.6% (12 of 125). Although all
      12 patients achieved an effective concentration for phenytoin therapy (>40
      umol/l) after the loading dose, no patient had their target concentration
      consistently maintained in the recommended therapeutic range (40 to 80 umol/l)
      throughout the seven-day monitoring period. There was wide fluctuation in
      phenytoin levels in the patients in this study. Twenty-two (18%) of the index
      patients had post-traumatic seizures, indicating a high prevalence for this
      study. Poor compliance with guidelines could possibly explain this phenomenon.
      Future studies are needed to look at the dosing and monitoring of phenytoin
      and/or alternative anti-seizure prophylaxis in patients with traumatic brain
      injury. 

PMID- 26310418
TI  - Revalidation: implications for Australian anaesthetists.
AB  - In early 2015, the Medical Board of Australia commissioned research into
      international revalidation models and what might be applicable for Australia.
      This review examines the implications for Australian anaesthetists. What problem
      is revalidation seeking to address? What is happening in similar countries? Is
      there an issue with Australian anaesthetists' performance? Isn't continuing
      professional development enough? Could the Medical Board target known high-risk
      doctors? What is the evidence for the benefit of revalidation? How is and how
      should the profession be involved? Revalidation has been introduced in other
      developed countries. It commonly involves continuing professional development,
      feedback from colleagues, co-workers and patients, clinical audit and peer
      review. Although its evidence base is limited, the General Medical Council in the
      United Kingdom is evaluating its revalidation system, which should provide useful
      guidance for other countries. Australian anaesthetists and their professional
      organisations must remain informed about, and engaged in, the national debate
      about revalidation, to ensure that any new process is workable for Australian
      anaesthesia practice. 

PMID- 26310419
TI  - A new ultrasound-guided dorsal penile nerve block technique for circumcision in
      children.

PMID- 26310420
TI  - Is there a place for bolus terlipressin use on the ward in postoperative
      hypotension not responding to fluid resuscitation?

PMID- 26310421
TI  - Current sedation practice for patients undergoing endobronchial ultrasound
      examination: a prospective cohort study.

PMID- 26310422
TI  - Functional and quality-of-life outcomes in older survivors of an Australian
      intensive care unit.

PMID- 26310423
TI  - Successful Maastricht Category 5 kidney donation after uncontrolled in-hospital
      cardiac arrest.

PMID- 26310424
TI  - Workforce shortages, heavy workloads and sudden deaths of anaesthetists in China.

PMID- 26310425
TI  - Drug labelling, compliance and system redesign.

PMID- 26310426
TI  - Lead poisoning in Australia associated with privately imported Ayurvedic
      complementary medicine.

PMID- 26310428
TI  - Neonatal Meckel diverticulum: Obstruction due to a short mesodiverticular band.
AB  - This is the first report of symptomatic Meckel diverticulum in a newborn, in
      which direct compression by a short mesodiverticular band (MDB) caused intestinal
      obstruction. A short MDB can cause intestinal obstruction due to direct
      compression. There are two mechanisms by which Meckel diverticulum with MDB can
      cause intestinal obstruction: internal hernia and direct compression. Onset of
      intestinal obstruction due to direct compression by a short MDB might be earlier
      than that for internal hernia with long MDB. 

PMID- 26310427
TI  - GMPPB-Associated Dystroglycanopathy: Emerging Common Variants with Phenotype
      Correlation.
AB  - Mutations in GDP-mannose pyrophosphorylase B (GMPPB), a catalyst for the
      formation of the sugar donor GDP-mannose, were recently identified as a cause of
      muscular dystrophy resulting from abnormal glycosylation of alpha-dystroglycan.
      In this series, we report nine unrelated individuals with GMPPB-associated
      dystroglycanopathy. The most mildly affected subject has normal strength at 25
      years, whereas three severely affected children presented in infancy with
      intellectual disability and epilepsy. Muscle biopsies of all subjects are
      dystrophic with abnormal immunostaining for glycosylated alpha-dystroglycan. This
      cohort, together with previously published cases, allows preliminary genotype
      phenotype correlations to be made for the emerging GMPPB common variants c.79G>C
      (p.D27H) and c.860G>A (p.R287Q). We observe that c.79G>C (p.D27H) is associated
      with a mild limb-girdle muscular dystrophy phenotype, whereas c.860G>A (p.R287Q)
      is associated with a relatively severe congenital muscular dystrophy typically
      involving brain development. Sixty-six percent of GMPPB families to date have one
      of these common variants. 

PMID- 26310429
TI  - Call for integrated approach to death education in UK medical schools.

PMID- 26310430
TI  - Risk of developing Parkinson's disease among patients with asthma: a nationwide
      longitudinal study.
AB  - BACKGROUND: A cross-sectional retrospective study suggested a link between
      allergic diseases and Parkinson's disease. However, the temporal association
      between asthma and Parkinson's disease remains unknown. METHODS: From the Taiwan
      National Health Insurance Research Database, 10 455 patients who were diagnosed
      with asthma between 1998 and 2008 and aged >=45 years and 41 820 age- and sex
      matched controls were selected for our study and observed until the end of 2011.
      Those who developed Parkinson's disease during the follow-up period were
      identified. We also examined the asthma severity, as indicated by the frequency
      of admission (times per year) for asthma exacerbation, and the risk of subsequent
      Parkinson's disease. RESULTS: Patients with asthma had an increased risk of
      developing Parkinson's disease (hazard ratio [HR]: 3.10, 95% confidence interval
      [CI]: 2.20-4.36) after we adjusted for demographic data, health system use,
      medical comorbidities, and medication use. Sensitivity tests yielded consistent
      findings after we excluded observations on the first year (HR: 2.90, 95% CI: 2.04
      4.13) and first 3 years (HR: 2.46, 95% CI: 1.64-3.69). Patients with asthma who
      had more frequent admissions (times per year) during the follow-up period
      exhibited a greater risk of subsequent Parkinson's disease (>2: HR: 16.42, 95%
      CI: 5.88-45.91; 1-2: 12.69, 95% CI: 5.03-31.71; 0-1: HR: 2.92, 95% CI: 1.91
      4.49). CONCLUSION: Patients with asthma had an elevated risk of developing
      Parkinson's disease later in life, and we observed a dose-dependent relationship
      between greater asthma severity and a higher risk of subsequent Parkinson's
      disease.

PMID- 26310431
TI  - Microbiome change by symbiotic invasion in lichens.
AB  - Lichens are obligate symbioses between fungi and green algae or cyanobacteria.
      Most lichens resynthesize their symbiotic thalli from propagules, but some
      develop within the structures of already existing lichen symbioses. Diploschistes
      muscorum starts as a parasite infecting the lichen Cladonia symphycarpa and
      gradually develops an independent Diploschistes lichen thallus. Here we studied
      how this process influences lichen-associated microbiomes and photobionts by
      sampling four transitional stages, at sites in Sweden and Germany, and
      characterizing their microbial communities using high-throughput 16S rRNA gene
      and photobiont-specific ITS rDNA sequencing, and fluorescence in situ
      hybridization. A gradual microbiome shift occurred during the transition, but
      fractions of Cladonia-associated bacteria were retained during the process of
      symbiotic reorganization. Consistent changes observed across sites included a
      notable decrease in the relative abundance of Alphaproteobacteria with a
      concomitant increase in Betaproteobacteria. Armatimonadia, Spartobacteria and
      Acidobacteria also decreased during the infection of Cladonia by Diploschistes.
      The lichens differed in photobiont specificity. Cladonia symphycarpa was
      associated with the same algal species at all sites, but Diploschistes muscorum
      had a flexible strategy with different photobiont combinations at each site. This
      symbiotic invasion system suggests that partners can be reorganized and selected
      for maintaining potential roles rather than depending on particular species.

PMID- 26310433
TI  - Enhanced tactile acuity through mental states.
AB  - Bodily training typically evokes behavioral and perceptual gains, enforcing
      neuroplastic processes and affecting neural representations. We investigated the
      effect on somatosensory perception of a three-day Zen meditation exercise, a
      purely mental intervention. Tactile spatial discrimination of the right index
      finger was persistently improved by only 6 hours of mental-sensory focusing on
      this finger, suggesting that intrinsic brain activity created by mental states
      can alter perception and behavior similarly to external stimulation. 

PMID- 26310432
TI  - What is the role of curvature on the properties of nanomaterials for biomedical
      applications?
AB  - The use of nanomaterials for drug delivery and theranostics applications is a
      promising paradigm in nanomedicine, as it brings together the best features of
      nanotechnolgy, molecular biology, and medicine. To fully exploit the synergistic
      potential of such interdisciplinary strategy, a comprehensive description of the
      interactions at the interface between nanomaterials and biological systems is not
      only crucial, but also mandatory. Routine strategies to engineer nanomaterial
      based drugs comprise modifying their surface with biocompatible and targeting
      ligands, in many cases resorting to modular approaches that assume additive
      behavior. However, emergent behavior can be observed when combining confinement
      and curvature. The final properties of functionalized nanomaterials become
      dependent not only on the properties of their constituents but also on the
      geometry of the nano-bio interface, and on the local molecular environment.
      Modularity no longer holds, and the coupling between interactions, chemical
      equilibrium, and molecular organization has to be directly addressed in order to
      design smart nanomaterials with controlled spatial functionalization envisioning
      optimized biomedical applications. Nanoparticle's curvature becomes an integral
      part of the design strategy, enabling to control and engineer the chemical and
      surface properties with molecular precision. Understanding how nanoparticle size,
      morphology, and surface chemistry are interrelated will put us one step closer to
      engineering nanobiomaterials capable of mimicking biological structures and their
      behaviors, paving the way into applications and the possibility to elucidate the
      use of curvature by biological systems. WIREs Nanomed Nanobiotechnol 2016, 8:334
      354. doi: 10.1002/wnan.1365 For further resources related to this article, please
      visit the WIREs website.

PMID- 26310434
TI  - Gold nanoparticle-mediated (GNOME) laser perforation: a new method for a high
      throughput analysis of gap junction intercellular coupling.
AB  - The present report evaluates the advantages of using the gold nanoparticle
      mediated laser perforation (GNOME LP) technique as a computer-controlled cell
      optoperforation to introduce Lucifer yellow (LY) into cells in order to analyze
      the gap junction coupling in cell monolayers. To permeabilize GM-7373 endothelial
      cells grown in a 24 multiwell plate with GNOME LP, a laser beam of 88 MUm in
      diameter was applied in the presence of gold nanoparticles and LY. After 10 min
      to allow dye uptake and diffusion through gap junctions, we observed a LY
      positive cell band of 179 +/- 8 MUm width. The presence of the gap junction
      channel blocker carbenoxolone during the optoperforation reduced the LY-positive
      band to 95 +/- 6 MUm. Additionally, a forskolin-related enhancement of gap
      junction coupling, recently found using the scrape loading technique, was also
      observed using GNOME LP. Further, an automatic cell imaging and a subsequent semi
      automatic quantification of the images using a java-based ImageJ-plugin were
      performed in a high-throughput sequence. Moreover, the GNOME LP was used on cells
      such as RBE4 rat brain endothelial cells, which cannot be mechanically scraped as
      well as on three-dimensionally cultivated cells, opening the possibility to
      implement the GNOME LP technique for analysis of gap junction coupling in
      tissues. We conclude that the GNOME LP technique allows a high-throughput
      automated analysis of gap junction coupling in cells. Moreover this non-invasive
      technique could be used on monolayers that do not support mechanical scraping as
      well as on cells in tissue allowing an in vivo/ex vivo analysis of gap junction
      coupling.

PMID- 26310435
TI  - Life form-specific gradients in compound-specific hydrogen isotope ratios of
      modern leaf waxes along a North American Monsoonal transect.
AB  - The use of hydrogen isotope ratios (delta(2)H) of sedimentary n-alkanes from leaf
      waxes has become an important tool for reconstructing paleoenvironmental and
      ancient hydrologic conditions. Studies of modern plant waxes can elucidate
      driving ecological mechanisms behind geologic deposits. Here, we used a transect
      across the North American Monsoon region of the western USA from Tucson, Arizona
      to Salt Lake City, Utah to study variations in leaf wax delta(2)H among co
      occurring plants. Three co-occurring life forms were selected: perennial shrub
      (rabbit brush, Chrysothamnus nauseosus; sagebrush, Artemisia tridentata); tree
      (Gambel's oak tree, Quercus gambelii); and annual (sunflower, Helianthus annuus).
      Our results showed that the distributions and abundances of n-alkanes in
      perennial plants were similar across all sites and generally did not vary with
      environmental conditions (e.g., precipitation and temperature). In contrast,
      variations in n-alkane delta(2)H were significantly correlated with the fraction
      of the annual precipitation coming during the summer monsoon period. We use a
      modified Craig-Gordon model to speculate on the possible drivers of the delta(2)H
      values of leaf wax n-alkanes of plants across the region. The model results
      suggest that the most likely explanation for variation in wax delta(2)H values
      was a combination of seasonal source water usage and subsequent environmental
      conditions. 

PMID- 26310436
TI  - Vitamin D supplementation for the prevention of childhood acute respiratory
      infections: a systematic review of randomised controlled trials.
AB  - Results from recent trials assessing the effect of vitamin D supplementation on
      the prevention of childhood acute respiratory infections (ARI) have been
      inconsistent. In the present study, we determined whether vitamin D
      supplementation prevents ARI in healthy children and repeated infections in
      children with previous ARI. We conducted a systematic literature search using
      MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. The
      search included only randomised controlled clinical trials (RCT) comparing
      vitamin D supplementation with either placebo or no intervention in children
      younger than 18 years of age. We identified seven RCT and found that the summary
      estimates were not statistically significantly associated with a reduction in the
      risk of ARI (relative risk (RR) 0.79, 95% CI 0.55, 1.13), all-cause mortality (RR
      1.18, 95% CI 0.71, 1.94), or the rate of hospital admission due to respiratory
      infection in healthy children (RR 0.95, 95% CI 0.72, 1.26). However, in children
      previously diagnosed with asthma, vitamin D supplementation resulted in a 74%
      reduction in the risk of asthma exacerbation (RR 0.26, 95% CI 0.11, 0.59; test of
      heterogeneity, I 2= 0.0%). Our findings indicate a lack of evidence supporting
      the routine use of vitamin D supplementation for the prevention of ARI in healthy
      children; however, they suggest that such supplementation may benefit children
      previously diagnosed with asthma. Due to the heterogeneity of the included
      studies and possible publication biases related to this field, these results
      should be interpreted with caution.

PMID- 26310437
TI  - Evidence for a Finite-Temperature Insulator.
AB  - In superconductors the zero-resistance current-flow is protected from dissipation
      at finite temperatures (T) by virtue of the short-circuit condition maintained by
      the electrons that remain in the condensed state. The recently suggested finite-T
      insulator and the "superinsulating" phase are different because any residual
      mechanism of conduction will eventually become dominant as the finite-T insulator
      sets-in. If the residual conduction is small it may be possible to observe the
      transition to these intriguing states. We show that the conductivity of the high
      magnetic-field insulator terminating superconductivity in amorphous indium-oxide
      exhibits an abrupt drop, and seem to approach a zero conductance at T < 0.04 K.
      We discuss our results in the light of theories that lead to a finite-T
      insulator. 

PMID- 26310438
TI  - Spindle-to-cortex communication in cleaving, polyspermic Xenopus eggs.
AB  - Mitotic spindles specify cleavage planes in early embryos by communicating their
      position and orientation to the cell cortex using microtubule asters that grow
      out from the spindle poles during anaphase. Chromatin also plays a poorly
      understood role. Polyspermic fertilization provides a natural experiment in which
      aster pairs from the same spindle (sister asters) have chromatin between them,
      whereas asters pairs from different spindles (nonsisters) do not. In frogs, only
      sister aster pairs induce furrows. We found that only sister asters recruited two
      conserved furrow-inducing signaling complexes, chromosome passenger complex (CPC)
      and Centralspindlin, to a plane between them. This explains why only sister pairs
      induce furrows. We then investigated factors that influenced CPC recruitment to
      microtubule bundles in intact eggs and a cytokinesis extract system. We found
      that microtubule stabilization, optimal starting distance between asters, and
      proximity to chromatin all favored CPC recruitment. We propose a model in which
      proximity to chromatin biases initial CPC recruitment to microtubule bundles
      between asters from the same spindle. Next a positive feedback between CPC
      recruitment and microtubule stabilization promotes lateral growth of a plane of
      CPC-positive microtubule bundles out to the cortex to position the furrow. 

PMID- 26310439
TI  - Modulation of receptor dynamics by the regulator of G protein signaling Sst2.
AB  - G protein-coupled receptor (GPCR) signaling is fundamental to physiological
      processes such as vision, the immune response, and wound healing. In the budding
      yeast Saccharomyces cerevisiae, GPCRs detect and respond to gradients of
      pheromone during mating. After pheromone stimulation, the GPCR Ste2 is removed
      from the cell membrane, and new receptors are delivered to the growing edge. The
      regulator of G protein signaling (RGS) protein Sst2 acts by accelerating GTP
      hydrolysis and facilitating pathway desensitization. Sst2 is also known to
      interact with the receptor Ste2. Here we show that Sst2 is required for proper
      receptor recovery at the growing edge of pheromone-stimulated cells. Mathematical
      modeling suggested pheromone-induced synthesis of Sst2 together with its
      interaction with the receptor function to reestablish a receptor pool at the site
      of polarized growth. To validate the model, we used targeted genetic
      perturbations to selectively disrupt key properties of Sst2 and its induction by
      pheromone. Together our results reveal that a regulator of G protein signaling
      can also regulate the G protein-coupled receptor. Whereas Sst2 negatively
      regulates G protein signaling, it acts in a positive manner to promote receptor
      retention at the growing edge. 

PMID- 26310440
TI  - Structural organization of nuclear lamins A, C, B1, and B2 revealed by
      superresolution microscopy.
AB  - The nuclear lamina is a key structural element of the metazoan nucleus. However,
      the structural organization of the major proteins composing the lamina is poorly
      defined. Using three-dimensional structured illumination microscopy and
      computational image analysis, we characterized the supramolecular structures of
      lamin A, C, B1, and B2 in mouse embryo fibroblast nuclei. Each isoform forms a
      distinct fiber meshwork, with comparable physical characteristics with respect to
      mesh edge length, mesh face area and shape, and edge connectivity to form faces.
      Some differences were found in face areas among isoforms due to variation in the
      edge lengths and number of edges per face, suggesting that each meshwork has
      somewhat unique assembly characteristics. In fibroblasts null for the expression
      of either lamins A/C or lamin B1, the remaining lamin meshworks are altered
      compared with the lamin meshworks in wild-type nuclei or nuclei lacking lamin B2.
      Nuclei lacking LA/C exhibit slightly enlarged meshwork faces and some shape
      changes, whereas LB1-deficient nuclei exhibit primarily a substantial increase in
      face area. These studies demonstrate that individual lamin isoforms assemble into
      complex networks within the nuclear lamina and that A- and B-type lamins have
      distinct roles in maintaining the organization of the nuclear lamina. 

PMID- 26310441
TI  - Apolar and polar transitions drive the conversion between amoeboid and
      mesenchymal shapes in melanoma cells.
AB  - Melanoma cells can adopt two functionally distinct forms, amoeboid and
      mesenchymal, which facilitates their ability to invade and colonize diverse
      environments during the metastatic process. Using quantitative imaging of single
      living tumor cells invading three-dimensional collagen matrices, in tandem with
      unsupervised computational analysis, we found that melanoma cells can switch
      between amoeboid and mesenchymal forms via two different routes in shape space-
      an apolar and polar route. We show that whereas particular Rho-family GTPases are
      required for the morphogenesis of amoeboid and mesenchymal forms, others are
      required for transitions via the apolar or polar route and not amoeboid or
      mesenchymal morphogenesis per se. Altering the transition rates between
      particular routes by depleting Rho-family GTPases can change the morphological
      heterogeneity of cell populations. The apolar and polar routes may have evolved
      in order to facilitate conversion between amoeboid and mesenchymal forms, as
      cells are either searching for, or attracted to, particular migratory cues,
      respectively.

PMID- 26310442
TI  - A comprehensive model to predict mitotic division in budding yeasts.
AB  - High-fidelity chromosome segregation during cell division depends on a series of
      concerted interdependent interactions. Using a systems biology approach, we built
      a robust minimal computational model to comprehend mitotic events in dividing
      budding yeasts of two major phyla: Ascomycota and Basidiomycota. This model
      accurately reproduces experimental observations related to spindle alignment,
      nuclear migration, and microtubule (MT) dynamics during cell division in these
      yeasts. The model converges to the conclusion that biased nucleation of
      cytoplasmic microtubules (cMTs) is essential for directional nuclear migration.
      Two distinct pathways, based on the population of cMTs and cortical dyneins,
      differentiate nuclear migration and spindle orientation in these two phyla. In
      addition, the model accurately predicts the contribution of specific classes of
      MTs in chromosome segregation. Thus we present a model that offers a wider
      applicability to simulate the effects of perturbation of an event on the
      concerted process of the mitotic cell division. 

PMID- 26310443
TI  - Loss of endogenous Nfatc1 reduces the rate of DMBA/TPA-induced skin
      tumorigenesis.
AB  - Immunosuppressive therapies using calcineurin inhibitors, such as cyclosporine A,
      are associated with a higher incidence of squamous cell carcinoma formation in
      mice and humans. Calcineurin is believed to suppress tumorigenesis in part
      through Nfatc1, a transcription factor expressed primarily in hair follicle bulge
      stem cells in mice. However, mice overexpressing a constitutively active Nfatc1
      isoform in the skin epithelium developed increased spontaneous skin squamous cell
      carcinomas. Because follicular stem cells can contribute to skin tumorigenesis,
      whether the endogenous expression of Nfatc1 inhibits or enhances skin
      tumorigenesis is unclear. Here we show that loss of the endogenous expression of
      Nfatc1 suppresses the rate of DMBA/TPA-induced skin tumorigenesis. Inducible
      deletion of Nfatc1 in follicular stem cells before tumor initiation significantly
      reduces the rate of tumorigenesis and the contribution of follicular stem cells
      to skin tumors. We find that skin tumors from mice lacking Nfatc1 display reduced
      Hras codon 61 mutations. Furthermore, Nfatc1 enhances the expression of genes
      involved in DMBA metabolism and increases DMBA-induced DNA damage in
      keratinocytes. Together these data implicate Nfatc1 in the regulation of skin
      stem cell-initiated tumorigenesis via the regulation of DMBA metabolism. 

PMID- 26310444
TI  - Modeling the roles of protein kinase Cbeta and eta in single-cell wound repair.
AB  - Wounded cells such as Xenopus oocytes respond to damage by assembly and closure
      of an array of actin filaments and myosin-2 controlled by Rho GTPases, including
      Rho and Cdc42. Rho and Cdc42 are patterned around wounds in a characteristic
      manner, with active Rho concentrating in a ring-like zone inside a larger, ring
      like zone of active Cdc42. How this patterning is achieved is unknown, but Rho
      and Cdc42 at wounds are subject to regulation by other proteins, including the
      protein kinases C. Specifically, Cdc42 and Rho activity are enhanced by PKCbeta
      and inhibited by PKCeta. We adapt a mathematical model of Simon and coworkers to
      probe the possible roles of these kinases. We show that PKCbeta likely affects
      the magnitude of positive Rho-Abr feedback, whereas PKCeta acts on Cdc42
      inactivation. The model explains both qualitative and some overall quantitative
      features of PKC-Rho GTPase regulation. It also accounts for the previous,
      peculiar observation that ~ 20% of cells overexpressing PKCeta display zone
      inversions--that is, displacement of active Rho to the outside of the active
      Cdc42.

PMID- 26310445
TI  - Experimental testing of a new integrated model of the budding yeast Start
      transition.
AB  - The cell cycle is composed of bistable molecular switches that govern the
      transitions between gap phases (G1 and G2) and the phases in which DNA is
      replicated (S) and partitioned between daughter cells (M). Many molecular details
      of the budding yeast G1-S transition (Start) have been elucidated in recent
      years, especially with regard to its switch-like behavior due to positive
      feedback mechanisms. These results led us to reevaluate and expand a previous
      mathematical model of the yeast cell cycle. The new model incorporates Whi3
      inhibition of Cln3 activity, Whi5 inhibition of SBF and MBF transcription
      factors, and feedback inhibition of Whi5 by G1-S cyclins. We tested the accuracy
      of the model by simulating various mutants not described in the literature. We
      then constructed these novel mutant strains and compared their observed
      phenotypes to the model's simulations. The experimental results reported here led
      to further changes of the model, which will be fully described in a later
      article. Our study demonstrates the advantages of combining model design,
      simulation, and testing in a coordinated effort to better understand a complex
      biological network. 

PMID- 26310446
TI  - Late steps in cytoplasmic maturation of assembly-competent axonemal outer arm
      dynein in Chlamydomonas require interaction of ODA5 and ODA10 in a complex.
AB  - Axonemal dyneins are multisubunit enzymes that must be preassembled in the
      cytoplasm, transported into cilia by intraflagellar transport, and bound to
      specific sites on doublet microtubules, where their activity facilitates
      microtubule sliding-based motility. Outer dynein arms (ODAs) require assembly
      factors to assist their preassembly, transport, and attachment to cargo (specific
      doublet A-tubule sites). In Chlamydomonas, three assembly factors--ODA5, ODA8,
      and ODA10--show genetic interactions and have been proposed to interact in a
      complex, but we recently showed that flagellar ODA8 does not copurify with ODA5
      or ODA10. Here we show that ODA5 and ODA10 depend on each other for stability and
      coexist in a complex in both cytoplasmic and flagellar extracts.
      Immunofluorescence and immuno-electron microscopy reveal that ODA10 in flagella
      localizes strictly to a proximal region of doublet number 1, which completely
      lacks ODAs in Chlamydomonas. Studies of the in vitro binding of ODAs to axonemal
      doublets reveal a role for the ODA5/ODA10 assembly complex in cytoplasmic
      maturation of ODAs into a form that can bind to doublet microtubules.

PMID- 26310447
TI  - The interaction of Galpha13 with integrin beta1 mediates cell migration by
      dynamic regulation of RhoA.
AB  - Heterotrimeric G protein Galpha13 is known to transmit G protein-coupled receptor
      (GPCR) signals leading to activation of RhoA and plays a role in cell migration.
      The mechanism underlying the role of Galpha13 in cell migration, however, remains
      unclear. Recently we found that Galpha13 interacts with the cytoplasmic domain of
      integrin beta3 subunits in platelets via a conserved ExE motif. Here we show that
      a similar direct interaction between Galpha13 and the cytoplasmic domain of the
      integrin beta1 subunit plays a critical role in beta1-dependent cell migration.
      Point mutation of either glutamic acid in the Galpha13-binding (767)EKE motif in
      beta1 or treatment with a peptide derived from the Galpha13-binding sequence of
      beta1 abolished Galpha13-beta1 interaction and inhibited beta1 integrin-dependent
      cell spreading and migration. We further show that the Galpha13-beta1 interaction
      mediates beta1 integrin-dependent Src activation and transient RhoA inhibition
      during initial cell adhesion, which is in contrast to the role of Galpha13 in
      mediating GPCR-dependent RhoA activation. These data indicate that Galpha13 plays
      dynamic roles in both stimulating RhoA via a GPCR pathway and inhibiting RhoA via
      an integrin signaling pathway. This dynamic regulation of RhoA activity is
      critical for cell migration on beta1 integrin ligands. 

PMID- 26310448
TI  - The function and dynamics of the apical scaffolding protein E3KARP are regulated
      by cell-cycle phosphorylation.
AB  - We examine the dynamics and function of the apical scaffolding protein
      E3KARP/NHERF2, which consists of two PDZ domains and a tail containing an ezrin
      binding domain. The exchange rate of E3KARP is greatly enhanced during mitosis
      due to phosphorylation at Ser-303 in its tail region. Whereas E3KARP can
      substitute for the function of the closely related scaffolding protein
      EBP50/NHERF1 in the formation of interphase microvilli, E3KARP S303D cannot.
      Moreover, the S303D mutation enhances the in vivo dynamics of the E3KARP tail
      alone, whereas in vitro the interaction of E3KARP with active ezrin is unaffected
      by S303D, implicating another factor regulating dynamics in vivo. A-Raf is found
      to be required for S303 phosphorylation in mitotic cells. Regulation of the
      dynamics of EBP50 is known to be dependent on its tail region but modulated by
      PDZ domain occupancy, which is not the case for E3KARP. Of interest, in both
      cases, the mechanisms regulating dynamics involve the tails, which are the most
      diverged region of the paralogues and probably evolved independently after a gene
      duplication event that occurred early in vertebrate evolution. 

PMID- 26310449
TI  - Prehension Kinematics, Grasping Forces, and Independent Finger Control in Mildly
      Affected Patients with Essential Tremor.
AB  - Although the pathophysiology of essential tremor (ET), one of the most common
      movement disorders, is not fully understood, evidence increasingly points to
      cerebellar involvement. To confirm this connection, we assessed the everyday hand
      and finger movements of patients with ET, as these movements are known to be
      affected in cerebellar diseases. In 26 mildly affected patients with ET (compared
      to age- and gender-matched controls), kinematic and finger force parameters were
      assessed in a precision grip. In a second task, independent finger movements were
      recorded. The active finger had to press and release against a force-sensitive
      keypad while the other fingers stayed inactive. Finally, control of grip force to
      movement-induced, self-generated load changes was studied. Transport and shaping
      components during prehension were significantly impaired in patients with ET
      compared to controls. No significant group differences were observed in
      independent finger movements and grip force adjustments to self-generated load
      force changes. However, in the latter two tasks, more severely affected ET
      patients performed worse than less affected. Although observed deficits in hand
      and finger movement tasks were small, they are consistent with cerebellar
      dysfunction in ET. Findings need to be confirmed in future studies examining more
      severely affected ET patients. 

PMID- 26310451
TI  - Differences in Clinicopathology of Early Gastric Carcinoma between Proximal and
      Distal Location in 438 Chinese Patients.
AB  - Early gastric carcinoma (EGC) in Chinese patients remains poorly understood and
      endoscopic therapy has not been well established. Here, we compared endoscopic
      and clinicopathologic features between early proximal gastric carcinoma (PGC, n =
      131) and distal gastric carcinoma (DGC, n = 307) in consecutive 438 EGCs
      diagnosed with the WHO criteria. By endoscopy, PGCs showed protruding and
      elevated patterns in 61.9%, while depressed and excavated patterns in 33.6%,
      which were significantly different from those (32.6% and 64.5%) in DGCs. PGCs
      were significantly smaller (1.9 cm in average, versus 2.2 cm in DGCs), invaded
      deeper (22.9% into SM2, versus 13% in DGCs), but had fewer (2.9%, versus 16.7% in
      DGCs) lymph node metastases. Papillary adenocarcinoma was significantly more
      frequent (32.1%, versus 12.1% in DGCs), as were mucinous and neuroendocrine
      carcinomas, carcinoma with lymphoid stroma (6.9%, versus 1.6% in DGCs); but
      poorly cohesive carcinoma was significantly less frequent (5.3%, versus 35.8% in
      DGCs). The overall 5-year survival rate was 92.9% in EGCs, and PGC patients
      showed shorter (42.4 months, versus 48.3 in DGCs) survival. Papillary and
      micropapillary adenocarcinomas and nodal metastasis were independent risk factors
      for worse survival in EGCs. EGCs in Chinese were heterogeneous with significant
      differences in endoscopy and clinicopathology between PGC and DGC. 

PMID- 26310453
TI  - High Energy Density Aqueous Electrochemical Capacitors with a KI-KOH Electrolyte.
AB  - We report a new electrochemical capacitor with an aqueous KI-KOH electrolyte that
      exhibits a higher specific energy and power than the state-of-the-art nonaqueous
      electrochemical capacitors. In addition to electrical double layer capacitance,
      redox reactions in this device contribute to charge storage at both positive and
      negative electrodes via a catholyte of IOx-/I- couple and a redox couple of
      H2O/Had, respectively. Here, we, for the first time, report utilizing IOx-/I-
      redox couple for the positive electrode, which pins the positive electrode
      potential to be 0.4-0.5 V vs Ag/AgCl. With the positive electrode potential
      pinned, we can polarize the cell to 1.6 V without breaking down the aqueous
      electrolyte so that the negative electrode potential could reach -1.1 V vs
      Ag/AgCl in the basic electrolyte, greatly enhancing energy storage. Both mass
      spectroscopy and Raman spectrometry confirm the formation of IO3- ions (+5) from
      I- (-1) after charging. Based on the total mass of electrodes and electrolyte in
      a practically relevant cell configuration, the device exhibits a maximum specific
      energy of 7.1 Wh/kg, operates between -20 and 50  degrees C, provides a maximum
      specific power of 6222 W/kg, and has a stable cycling life with 93% retention of
      the peak specific energy after 14,000 cycles.

PMID- 26310452
TI  - A Bayesian cost-effectiveness analysis of a telemedicine-based strategy for the
      management of sleep apnoea: a multicentre randomised controlled trial.
AB  - BACKGROUND: Compliance with continuous positive airway pressure (CPAP) therapy is
      essential in patients with obstructive sleep apnoea (OSA), but adequate control
      is not always possible. This is clinically important because CPAP can reverse the
      morbidity and mortality associated with OSA. Telemedicine, with support provided
      via a web platform and video conferences, could represent a cost-effective
      alternative to standard care management. AIM: To assess the telemedicine impact
      on treatment compliance, cost-effectiveness and improvement in quality of life
      (QoL) when compared with traditional face-to-face follow-up. METHODS: A
      randomised controlled trial was performed to compare a telemedicine-based CPAP
      follow-up strategy with standard face-to-face management. Consecutive OSA
      patients requiring CPAP treatment, with sufficient internet skills and who agreed
      to participate, were enrolled. They were followed-up at 1, 3 and 6 months and
      answered surveys about sleep, CPAP side effects and lifestyle. We compared CPAP
      compliance, cost-effectiveness and QoL between the beginning and the end of the
      study. A Bayesian cost-effectiveness analysis with non-informative priors was
      performed. RESULTS: We randomised 139 patients. At 6 months, we found similar
      levels of CPAP compliance, and improved daytime sleepiness, QoL, side effects and
      degree of satisfaction in both groups. Despite requiring more visits, the
      telemedicine group was more cost-effective: costs were lower and differences in
      effectiveness were not relevant. CONCLUSIONS: A telemedicine-based strategy for
      the follow-up of CPAP treatment in patients with OSA was as effective as standard
      hospital-based care in terms of CPAP compliance and symptom improvement, with
      comparable side effects and satisfaction rates. The telemedicine-based strategy
      had lower total costs due to savings on transport and less lost productivity
      (indirect costs). TRIAL REGISTER NUMBER: NCT01716676.

PMID- 26310454
TI  - Prevalence, repairs and complications of hypospadias: an Australian population
      based study.
AB  - OBJECTIVE: To investigate hypospadias' prevalence and trends, rate of surgical
      repairs and post-repair complications in an Australian population. METHODS:
      Hypospadias cases were identified from all live-born infants in New South Wales,
      Australia, during the period 2001-2010, using routinely collected birth and
      hospital data. Prevalence, trends, surgical procedures or repairs, hospital
      admissions and complications following surgery were evaluated. Risk factors for
      reoperation and complications were assessed using multivariate logistic
      regression. RESULTS: There were 3186 boys with hypospadias in 2001-2010. Overall
      prevalence was 35.1 per 10,000 live births and remained constant during the study
      period. Proportions of anterior, middle, proximal and unspecified hypospadias
      were 41.3%, 26.2%, 5.8% and 26.6%, respectively. Surgical procedures were
      performed in 1945 boys (61%), with 1718 primary repairs. The overall post-surgery
      complication rate involving fistulas or strictures was 13%, but higher (33%) for
      proximal cases. Complications occurred after 1 year post-repair in 52.3% of cases
      and up to 5 years. Boys with proximal or middle hypospadias were at increased
      risk of reoperation or complications, but age at primary repair did not affect
      the outcome. CONCLUSION: One in 285 infants were affected with hypospadias, 60%
      required surgical repair or correction and one in eight experienced
      complications. The frequency of late complications would suggest that clinical
      review should be maintained for >1 year post-repair.

PMID- 26310455
TI  - Solar PAR and UVR modify the community composition and photosynthetic activity of
      sea ice algae.
AB  - The effects of increased photosynthetically active radiation (PAR) and
      ultraviolet radiation (UVR) on species diversity, biomass and photosynthetic
      activity were studied in fast ice algal communities. The experimental set-up
      consisted of nine 1.44 m(2) squares with three treatments: untreated with natural
      snow cover (UNT), snow-free (PAR + UVR) and snow-free ice covered with a UV
      screen (PAR). The total algal biomass, dominated by diatoms and dinoflagellates,
      increased in all treatments during the experiment. However, the smaller biomass
      growth in the top 10-cm layer of the PAR + UVR treatment compared with the PAR
      treatment indicated the negative effect of UVR. Scrippsiella complex (mainly
      Scrippsiella hangoei, Biecheleria baltica and Gymnodinium corollarium) showed UV
      sensitivity in the top 5-cm layer, whereas Heterocapsa arctica ssp. frigida and
      green algae showed sensitivity to both PAR and UVR. The photosynthetic activity
      was highest in the top 5-cm layer of the PAR treatment, where the biomass of the
      pennate diatom Nitzschia frigida increased, indicating the UV sensitivity of this
      species. This study shows that UVR is one of the controlling factors of algal
      communities in Baltic Sea ice, and that increased availability of PAR together
      with UVR exclusion can cause changes in algal biomass, photosynthetic activity
      and community composition. 

PMID- 26310456
TI  - Transcriptional suppression of CTP:phosphoethanolamine cytidylyltransferase by 25
      hydroxycholesterol is mediated by nuclear factor-Y and Yin Yang 1.
AB  - Pcyt2 (CTP:phosphoethanolamine cytidylyltransferase) is the rate-limiting enzyme
      in mammalian PE (phosphatidylethanolamine) biosynthesis. Previously, we reported
      that Pcyt2 mRNA levels increased in several types of cells after serum
      starvation, an effect that could be suppressed by supplementation with low
      density lipoprotein or 25-HC (25-hydroxycholesterol). Transcription of Hmgcr,
      which encodes 3-hydroxy-3-methylglutaryl-CoA reductase, is also suppressed by 25
      HC in the same dose-dependent manner. Nevertheless, a sterol-regulatory element
      was not detected in the Pcyt2 promoter region. The important element for
      transcriptional control of Pcyt2 by 25-HC (1.25 MUM) was determined to reside
      between -56 and -36 on the basis of analysis with several Pcyt2 promoter deletion
      luciferase reporters in NIH 3T3 cells. Using the yeast one-hybrid system, we
      found that NF-Y (nuclear factor-Y) binds at C(-37)CAAT(-41) and YY1 (Yin Yang1)
      binds at C(-42)AT(-40) in the Pcyt2 promoter. Endogenous NF-Y and YY1 bind
      clearly and competitively to these sites and are important for basal Pcyt2
      transcription. Moreover, NF-Y binds to the Hmgcr promoter at C(-14)CA(-12) in gel
      shift analysis, and suppression of the basal luciferase activity of the Hmgcr
      promoter-reporter construct (-30/+61) by 25-HC was abolished when C(-14)CA(-12)
      was mutated. Furthermore, transcriptional suppression of Pcyt2 by 25-HC was
      reduced following knockdown targeting of NF-YA or YY1. ChIP analysis revealed
      that 25-HC inhibited the interaction between NF-Y and RNA polymerase II on the
      Pcyt2 and Hmgcr promoters. On the basis of these results, we conclude that NF-Y
      and YY1 are important for the basal transcription of Pcyt2 and that NF-Y is
      involved in the inhibitory effects of 25-HC on Pcyt2 transcription.

PMID- 26310457
TI  - Intersubjective Interaction Between Deaf Parents/Deaf Infants During the Infant's
      First 18 Months.
AB  - This study is part of a larger longitudinal project with the aim of focusing
      early social interaction and development of mentalizing ability in 12 deaf
      infants, including the interaction between the infants and their deaf parents.
      The aim of the present paper is to describe early social interaction and moments
      of intersubjectivity between the deaf infants and their deaf parents during the
      first 18 months of the infant's life. The study is focused on the dyadic
      interaction rather than on the behaviors of the infant and the caregiver
      separately. In the analysis, the Intersubjective Developmental Theory Model
      (Loots, Devise, & Sermijn, 2003) and the definitions of moments of
      intersubjectivity (Loots, Devise, & Jacquet, 2005) were used. The findings show
      that the participating infants follow a typical developmental trajectory of
      intersubjectivity, both with regard to developmental stages and age. This
      development is supported by a visual, simultaneous way of communicating by gaze
      rather than having constant eye contact. Parents use complex visual communication
      skills in maintaining joint attention and also expect the infant to grasp the
      meaning of the interaction by use of gaze contact. 

PMID- 26310458
TI  - Effects of the Dietary omega3:omega6 Fatty Acid Ratio on Body Fat and
      Inflammation in Zebrafish (Danio rerio).
AB  - The diets of populations in industrialized nations have shifted to dramatically
      increased consumption of omega6 polyunsaturated fatty acids (PUFA), with a
      corresponding decrease in the consumption of omega3 PUFA. This dietary shift may
      be related to observed increases in obesity, chronic inflammation, and
      comorbidities in the human population. We examined the effects of omega3:omega6
      fatty acid ratios in the context of constant total dietary lipid on the growth,
      total body fat, and responses of key inflammatory markers in adult zebrafish
      (Danio rerio). Zebrafish were fed diets in which the omega3:omega6 PUFA ratios
      were representative of those in a purported ancestral diet (1:2) and more
      contemporary Western diets (1:5 and 1:8). After 5 mo, weight gain (fat free mass)
      of zebrafish was highest for those that received the 1:8 ratio treatment, but
      total body fat was lowest at this ratio. Measured by quantitative real-time RT
      PCR, mRNA levels from liver samples of 3 chronic inflammatory response genes (C
      reactive protein, serum amyloid A, and vitellogenin) were lowest at the 1:8
      ratio. These data provide evidence of the ability to alter zebrafish growth and
      body composition through the quality of dietary lipid and support the application
      of this model to investigations of human health and disease related to fat
      metabolism. 

PMID- 26310459
TI  - Electrocardiographic Characterization of Cardiac Hypertrophy in Mice that
      Overexpress the ErbB2 Receptor Tyrosine Kinase.
AB  - Electrocardiography is an important method for evaluation and risk stratification
      of patients with cardiac hypertrophy. We hypothesized that the recently developed
      transgenic mouse model of cardiac hypertrophy (ErbB2(tg)) will display distinct
      ECG features, enabling WT (wild type) mice to be distinguished from transgenic
      mice without using conventional PCR genotyping. We evaluated more than 2000 mice
      and developed specific criteria for genotype determination by using cageside ECG,
      during which unanesthetized mice were manually restrained for less than 1 min.
      Compared with those from WT counterparts, the ECG recordings of ErbB2(tg) mice
      were characterized by higher P- and R-wave amplitudes, broader QRS complexes,
      inverted T waves, and ST interval depression. Pearson's correlation matrix
      analysis of combined WT and ErbB2(tg) data revealed significant correlation
      between heart weight and the ECG parameters of QT interval (corrected for heart
      rate), QRS interval, ST height, R amplitude, P amplitude, and PR interval. In
      addition, the left ventricular posterior wall thickness as determined by
      echocardiography correlated with ECG-determined ST height, R amplitude, QRS
      interval; echocardiographic left ventricular mass correlated with ECG-determined
      ST height and PR interval. In summary, we have determined phenotypic ECG criteria
      to differentiate ErbB2(tg) from WT genotypes in 98.8% of mice. This inexpensive
      and time-efficient ECG-based phenotypic method might be applied to differentiate
      between genotypes in other rodent models of cardiac hypertrophy. Furthermore,
      with appropriate modifications, this method might be translated for use in other
      species. 

PMID- 26310460
TI  - Effect of Chronic Uremia on the Cell Surface Expression of B7 Family
      Costimulatory Molecules in an HLA-A2 Transgenic Mouse Model of Chronic Kidney
      Disease.
AB  - Uremia due to chronic kidney disease (CKD) in humans is associated with immune
      dysfunction, increased susceptibility to infections, immune-activation-associated
      inflammation, and poor responses to vaccines. The pathophysiologic basis of these
      immune defects is hypothesized to be associated with a wide range of immunologic
      abnormalities, including an inability to sufficiently express the B7 family (B7
      1, CD80; B7-2, CD86) of T-cell costimulatory molecules. However, testing the
      hypothesis that a state of chronic uremia contributes to attenuated expression of
      CD80 or CD86 has been difficult because few animal models faithfully recapitulate
      the immune defects observed in human CKD patients. We used a humanized mouse in a
      model of surgically induced renal failure and secondary chronic uremia to
      evaluate the effect of uremia on the expression of these markers. In a manner
      that resembles the changes observed in CKD patients, surgically induced CKD in
      mice resulted in decreased costimulatory CD86 expression compared with that in
      sham-operated controls. Immunodeficiency was functionally demonstrated in this
      mouse model by documenting an attenuated immune response to a cholera-toxin-based
      hepatitis B vaccine. This model will be useful for investigating the mechanisms
      involved in chronic uremia-associated immunodeficiency, poor response to
      vaccination, and problems associated with immunization of CKD patients. 

PMID- 26310461
TI  - Acute and Chronic Airway Disease After Human Respiratory Syncytial Virus
      Infection in Cotton Rats (Sigmodon hispidus).
AB  - Infection with respiratory syncytial virus (RSV) generally presents as a mild,
      upper airway disease in human patients but may cause severe lower airway disease
      in the very young and very old. Progress toward understanding the mechanisms of
      RSV pathogenesis has been hampered by a lack of relevant rodent models. Mice, the
      species most commonly used in RSV research, are resistant to upper respiratory
      infection and do not recapitulate the pattern of virus spread in the human host.
      To address the need for better rodent models of RSV infection, we have
      characterized the acute and chronic pathology of RSV infection of a relatively
      permissive host, cotton rats (Sigmodon hispidus). We demonstrate that virus
      delivered to the upper airway results in widespread RSV replication in the
      ciliated respiratory epithelial cells of the nasal cavity and, to a lesser
      extent, of the lung. Although acute inflammation is relatively mild and rapidly
      eliminated after viral clearance, chronic, eosinophilic lung pathology persists.
      These data support the use of cotton rats as a robust rodent model of human RSV
      disease, including the association between RSV pneumonia and subsequent
      development of allergic asthma. 

PMID- 26310462
TI  - Spontaneous Dilated Cardiomyopathy and Right-Sided Heart Failure as a
      Differential Diagnosis for Hepatosis Dietetica in a Production Pig.
AB  - An experimentally naive 37.7-kg Yorkshire-crossbred gilt died unexpectedly 2 d
      after arrival. Necropsy revealed severe dilated cardiomyopathy characterized
      grossly by markedly dilated ventricles and thinned ventricular walls and
      interventricular septum. Histologically there was multifocal myofiber attenuation
      and patchy loss of myofiber cross striations. The liver contained submassive to
      massive, diffuse hepatic centrilobular hemorrhage and degeneration. These lesions
      supported a diagnosis of dilated cardiomyopathy with right heart failure and
      secondary hepatic degeneration due to marked acute passive congestion. To our
      knowledge, this case is the first report of spontaneous dilated cardiomyopathy in
      swine and represents a potential diagnostic challenge regarding the
      differentiation of the cardiac-associated liver lesion from hepatosis dietetica.
      The diagnosis of dilated cardiomyopathy and right-sided heart failure was
      supported by the character of the hepatic lesion, absence of typical gross or
      histologic lesions of mulberry heart disease, and normal selenium levels. 

PMID- 26310463
TI  - Age- and Sex-Associated Effects on Acute-Phase Proteins in Gottingen Minipigs.
AB  - Gottingen minipigs are a useful model for diseases having an inflammatory
      component, and the associated use of acute-phase proteins (APP) as biomarkers of
      inflammation warrants establishment of their reference ranges. The objective of
      this study was to establish reference values for selected APP in Gottingen
      minipigs and to investigate the effects of age, sex, and various stimuli on these
      ranges. Serum concentrations of C-reactive protein (CRP), serum amyloid A (SAA),
      haptoglobin, pig major acute-phase protein (PMAP), albumin, and porcine alpha-1
      acid glycoprotein (PAGP) were evaluated in 4 age groups (6, 16, 24 and 40-48 wk)
      of male and female Gottingen minipigs. In addition, minipigs were tested under 2
      housing conditions, after acute LPS challenge, and after diet-induced obesity
      with and without mild diabetes. Changing the pigs to a new environment induced
      significant increases in CRP, PMAP, haptoglobin and PAGP and a decrease in
      albumin. An acute LPS stimulus increased CRP, PMAP, haptoglobin, and SAA; PAGP
      was unchanged and albumin decreased. Obese pigs with and without diabetes showed
      increases in CRP and PAGP, albumin decreased, and haptoglobin and SAA were
      unchanged. PMAP was increased only in obese pigs without diabetes. In conclusion,
      reference values for CRP, PMAP, haptoglobin, SAA, PAGP and albumin were
      established for male and female Gottingen minipigs of different ages. These APP
      were influenced by age and sex, underlining the importance of considering these
      factors when designing and interpreting studies including aspects of
      inflammation. In addition, an APP response was verified after both acute and
      chronic stimuli. 

PMID- 26310465
TI  - Solitary Osteochondroma in a Ring-Tailed Lemur (Lemur catta).
AB  - A 20-y-old, male, ring-tailed lemur (Lemur catta) presented with a large, firm
      mass on the proximal caudolateral left femur. The animal displayed no clinical
      signs associated with the mass. Radiographs revealed a mineralized mass
      protruding from the femur, with an intact femoral cortex. Histopathology
      diagnosed osteochondroma in view of the presence of a peripheral layer of
      cartilage with progressive endochondral ossification and typical remodeling of
      bony trabeculae. The mass grew quickly after the initial biopsy, and a second
      surgery to debulk 95% of the tumor was performed. Histopathologic features of the
      larger samples were similar to those of the initial biopsies, with the cartilage
      layer being discontinuous and development of bone from some borders progressing
      directly from a periost-like layer. Nineteen months after the second surgery, the
      mass had regrown and extended further proximally on the femur toward the
      epiphysis, but the animal remained asymptomatic, and additional debulking was not
      attempted. This report is the first description of an osteochondroma in a
      prosimian and describes unique behavior of the tumor compared with
      osteochondromas found in humans, dogs, and cats. 

PMID- 26310464
TI  - Diffraction-Enhanced Computed Tomographic Imaging of Growing Piglet Joints by
      Using a Synchrotron Light Source.
AB  - The objective of this project was to develop and test a new technology for
      imaging growing joints by means of diffraction-enhanced imaging (DEI) combined
      with CT and using a synchrotron radiation source. DEI-CT images of an explanted 4
      wk-old piglet stifle joint were acquired by using a 40-keV beam. The series of
      scanned slices was later 'stitched' together, forming a 3D dataset. High
      resolution DEI-CT images demonstrated fine detail within all joint structures and
      tissues. Striking detail of vasculature traversing between bone and cartilage, a
      characteristic of growing but not mature joints, was demonstrated. This report
      documents for the first time that DEI combined with CT and a synchrotron
      radiation source can generate more detailed images of intact, growing joints than
      can currently available conventional imaging modalities. 

PMID- 26310466
TI  - New-Onset Diabetes Mellitus After Transplantation in a Cynomolgus Macaque (Macaca
      fasicularis).
AB  - A 5.5-y-old intact male cynomolgus macaque (Macaca fasicularis) presented with
      inappetence and weight loss 57 d after heterotopic heart and thymus
      transplantation while receiving an immunosuppressant regimen consisting of
      tacrolimus, mycophenolate mofetil, and methylprednisolone to prevent graft
      rejection. A serum chemistry panel, a glycated hemoglobin test, and urinalysis
      performed at presentation revealed elevated blood glucose and glycated hemoglobin
      (HbA1c) levels (727 mg/dL and 10.1%, respectively), glucosuria, and ketonuria.
      Diabetes mellitus was diagnosed, and insulin therapy was initiated immediately.
      The macaque was weaned off the immunosuppressive therapy as his clinical
      condition improved and stabilized. Approximately 74 d after discontinuation of
      the immunosuppressants, the blood glucose normalized, and the insulin therapy was
      stopped. The animal's blood glucose and HbA1c values have remained within normal
      limits since this time. We suspect that our macaque experienced new-onset
      diabetes mellitus after transplantation, a condition that is commonly observed in
      human transplant patients but not well described in NHP. To our knowledge, this
      report represents the first documented case of new-onset diabetes mellitus after
      transplantation in a cynomolgus macaque. 

PMID- 26310467
TI  - [Challenges faced by public health research organization in the context of
      translational research].
AB  - Translational research in public health (TRPH) increasingly attracted attention.
      Focus of TRPH is not only patients, it also emphasizes to promote health for all
      society and whole population. Therefore, TRPH is more complicated, involves multi
      disciplines and multi-sectors. This paper analyzed the conception, features of
      TRPH, and challenges faced by research organization of public health. 

PMID- 26310468
TI  - [Focus on the feeding behaviors inducing obesity and their regulation
      strategies].
AB  - Obesity has become a worldwide public health concern. In particular, obesity
      caused by excessive energy intake was widespread which has strong causal
      relationship with food preference behaviors. In this review, we would briefly
      talk about characteristics of feeding behaviors inducing obesity, as well as the
      possible neurophysiological mechanisms involved in food preference formation and
      development. Meantime, we would introduce some regulation strategies to deal with
      obesity which mainly based on the current feeding behaviors of the obese. 

PMID- 26310469
TI  - [A cross-sectional study on health management service for hypertension and
      diabetes, Sichuan province, 2014].
AB  - OBJECTIVE: To investigate the quantity, quality and effect of health management
      service project for patients with hypertension and diabetes in basic public
      health service project of Sichuan province. METHODS: 44 health clinics or
      community health service center, 22 counties and 11 cities was extracted by
      method of multistage stratified sampling on March, 2014. In each institution we
      sampled 10 resident health record of hyperpietic and 10 of diabetic. Number of
      managed patients was recorded to calculate the rate of health management.
      Telephone survey was used to judge the accuracy and standardability of services
      the patients received according to the national basic public health service
      specifications. We compared the satisfaction rate and blood pressure/blood sugar
      control rate of patients which had accurate record to which had not, and which
      got normative services to which didn't. RESULTS: 33.8% (69 680/206 154) of the
      hyperpietics and 24.0% (25 562/106 508) of the diabetics were managed. 81.16%
      (702/865) of the records were with accurate information. 74.36% (522/702) of the
      patients received normative services. Blood pressure was well controlled in
      86.92% (299/344) of the hyperpietics, and FPG was well controlled in 85.46%
      (288/337) of the diabetics. The satisfaction rate was 94.58% (698/738). The
      satisfaction rate of patients which had accurate record was 98.69% (677/686), but
      of which had not was just 40.38% (21/52) (chi2 = 320.52, P < 0.001). The
      satisfaction rate of patients which got normative services was 99.22% (508/512),
      and of which did not get was 97.13% (169/174) (chi2 = 2.92, P = 0.087).
      CONCLUSION: The quality of managed chronic patients was well, and got obvious
      effect. Measures need to implement for increasing the management rate, accuracy
      and standardability of health management services for hyperpietic and diabetic.

PMID- 26310470
TI  - [Relationship between the clustering of risk factors and the prevalence of
      hypertension among planned pregnancy couples in Chongqing].
AB  - OBJECTIVE: To investigate relationship between the clustering of risk factors and
      the prevalence of hypertension among planned pregnancy couples in Chongqing.
      METHODS: From April to December 2013, proportional multi-stage stratified cluster
      randomized sampling method was used to collect 11 953 pairs of planned pregnancy
      couples from 19 districts (counties) in Chongqing for questionnaire, physical
      examination and blood glucose test. Univariate and multivariate statistical
      methods were used to describe the correlation between risk factors clustering of
      hypertension, prevalence of hypertension was standardized by the 6th census data
      of Chongqing city. RESULTS: The standardized prevalence of hypertension of
      planned pregnancy couples in Chongqing was 15.6% (95% CI: 15.1%-16.0%), while the
      standardized prevalence of husbands was 16.7% (95% CI: 16.0%-17.4%), and of wives
      14.2% (95% CI: 13.6%-14.9%). The three highest proportion of risk factors
      surveyed were the economic pressures (95.1%, 22 732/23 906), family history
      (24.9%, 5 950/23 906), overweight and obesity (22.3%, 5 341/23 906). Husband
      group, the risk of men with family history, overweight, obesity, smoking, alcohol
      consumption, with economic pressure were higher than those who without family
      history, normal weight, no smoking, no drinking, no economic pressure by
      2.49(1.88-3.31), 1.85(1.68-2.03), 1.29(1.22-1.37), 1.16(1.11-1.23), 1.09 (1.03
      1.16) times. Wife group, the risk of women with family history, high blood sugar,
      alcohol, with economic pressure were higher than those who without family
      history, blood sugar normal, no drinking, no economic pressure by 3.07(2.43
      3.89), 2.92(2.52-3.38), 1.28(1.12-1.49), 1.21(1.05-1.39), 2.52(1.40-4.53) times.
      With the increased number of accumulation hypertension risk factors, the
      prevalence and hypertension associated OR value increased among husbands and
      wives. Husband with the aggregation number from 2 to 5 had the OR value (OR =
      3.45, 95% CI: 1.41-8.46), (OR = 5.68, 95% CI: 2.32-13.93), (OR = 9.61, 95% CI:
      3.92-23.59), (OR = 15.20, 95% CI: 6.10-37.87); Wife with the aggregation number
      from 2 to 4 had the OR value (OR = 3.85, 95% CI: 1.41-10.52), (OR = 6.18, 95% CI:
      2.23-17.15), (OR = 9.30, 95% CI: 3.15-27.48). CONCLUSION: Family history,
      overweight, obesity, smoking, alcohol consumption, excessive economic pressure
      were the major risk factors for hypertension among planned pregnancy couples in
      Chongqing. With the increase of the risk factors items numbers, the risk of
      hypertension increases.

PMID- 26310471
TI  - [The effects of exposure to the famine during early life with elevated resting
      heart rate in the adult].
AB  - OBJECTIVE: To investigate the association between exposure to the famine during
      early life and elevated resting heart rate (RHR) in adulthood. METHOD: From June
      2006 to October 2007, the employees of kailuan group who took part in the health
      examination were selected. Of those, 18 619 cases who was born during October 1,
      1956 to September 30, 1964 in Hebei province were finally included in the
      analysis based on the inclusion and exclusion criteria. All the subjects were
      received questionnaire survey, smoking and drinking, physical examination, Lab
      examination and the measurement of RHR. The subjects of famine exposure group (3
      190 cases) were born from October 1, 1959 to September 30, 1961, semi-exposure
      group (3 851 cases) were born from October 1, 1958 to September 30, 1959 and from
      October 1, 1961 to September 30, 1962, control group (11 578 cases) were born
      from October 1, 1956 to September 30, 1958 and from October 1, 1962 to September
      30, 1964. The RHR and the detection rate of elevated RHR were compared among the
      three groups. The Multivariate logistic regression model was used to analyze the
      association between of exposure to famine during early life and elevated RHR in
      adulthood. RESULTS: The RHR level was higher in famine exposure group and semi
      exposed group than control group, which were (74.34 +/- 9.71), (74.41 +/- 9.48)
      and (73.90 +/- 9.45) beat per minute (bpm) (P values were 0.003 and 0.020,
      respectively). In all of the subjects. The results of multivariate logistic
      regression showed that exposure of famine during early life increased the risk of
      elevated RHR in adulthood after adjustment for age, gender and other confounders
      (OR = 1.10, 95% CI: 1.01-1.21). In men, exposure of famine during early life also
      increased the risk of elevated RHR in adulthood (OR = 1.15, 95% CI: 1.04-1.28);
      In women, there was no association between the famine exposure and elevated RHR
      (OR = 0.92, 95% CI: 0.74-1.14). CONCLUSION: Exposure of famine during early life
      increases the risk of elevated RHR in adulthood. This negative effect existed
      mainly in the male.

PMID- 26310472
TI  - [Association between ambient air pollution and stroke mortality in Wuhan, China:
      A time-series analysis].
AB  - OBJECTIVE: Using time-series analyses to determine the association between
      ambient air pollution and stroke mortality in Jiang'an District of Wuhan, China
      from 2003 to 2010. METHODS: Data on daily stroke mortality for the period 2003
      January 1 to 2010 December 31 was obtained from Jiang'an District Center for
      Disease Control and Prevention, Wuhan and data on relevant air pollution and
      meteorological factors from the local municipal environmental monitoring center
      and meteorology bureau of Wuhan, respectively. Application of a time-series
      analysis in generalized additive model was applied to evaluate the association
      between air pollution and stroke mortality. RESULTS: Annual average
      concentrations of PM10, SO(2) and NO(2) during the study period were (115.0 +/-
      60.0), (50.2 +/- 33.7), and (57.6 +/- 25.3) ug/m3 respectively. The total stroke
      death was 9 204, including 4 495 women, and 7 628 people aged over 65-years old.
      In single-pollutant model, a 10 ug/m3 increase in previous day (lag 1 d) ambient
      pollutants was associated with 0.67% (95% CI: 0.25%-1.10%) excess risk in stroke
      mortality for PM10, 0.87% (95% CI: 0.13%-1.63%) excess risk for SO(2) and 2.07%
      (95% CI: 1.08%-3.07%) excess risk for NO(2), respectively. When co-pollutants
      were involved into the models, only NO(2) remained strongly associated with
      stroke mortality (beta = 2.07, 95% CI: 1.08-3.07, P < 0.001). A 10 ug/m3,
      increase of NO(2) in lag 1 d was associated with 1.77% (95% CI: 0.54%-3.01%),
      2.27% (95% CI: 0.98%-3.57%) and 2.00% (95% CI: 0.59%-3.43%) excess risk in stroke
      mortality, respectively, after adjusting for PM10, SO(2)th PM10 and SO(2) e
      specific and gender-specific analyses showed that the association between ambient
      air pollution and stroke mortality was stronger in the elderly (>= 65 years old)
      people and women. A 10 ug/m, increase of PM10, SO(2) NO(2) in lag 1 d was
      associated with excess stroke mortality of 0.97% (95% CI: 0.37%-1.57%), 1.73%
      (95% CI: 0.69%-2.78%) and 2.98% (95% CI: 1.59%-4.39%) for women, respectively and
      0.94% (95% CI: 0.47%-1.42%), 1.06% (95% CI: 0.23%-1.90%) and 2.50% (95% CI: 1.40%
      3.62%) for the elderly people (> 65 years old), respectively. CONCLUSION: PM10
      and gaseous pollutants (SO(2), NO(2)) were significant risk factors for acute
      stroke death, and people aged over 65-years old and women were more susceptible
      to the effect of ambient pollutants on stroke mortality.

PMID- 26310473
TI  - [Varicella breakthrough infection and vaccine effectiveness with 1-dose
      varicella].
AB  - OBJECTIVE: To evaluate the breakthrough varicella infection rate and varicella
      vaccine effectiveness (VE) among children who received 1-dose varicella vaccine.
      METHODS: A total of 57 180 subjects for the consecutive 4-year birth cohorts were
      selected from the local children born between 2007 and 2010 in Yinzhou District,
      Ninghai County and Yuyao City. And they were followed up for varicella from 2008
      to 2013. The recipients of the vaccinations were identified through Ningbo
      Immunization Information System and data on breakthrough infections among the
      recipients were collected by using China Information System for Disease Control
      and Prevention. The breakthrough varicella rate and the VE were calculated and
      the trends of them were described from 2008 to 2013 among 4-year birth cohorts.
      The cumulative incidence of varicella was compared between vaccinated and
      unvaccinated children among the consecutive 4-year birth cohorts. RESULTS: The
      rate of varicella vaccine coverage, vaccine cumulative incidence among the
      cohorts was 96.74% (55 317/57 180) and 0.56% (321/57 180). The breakthrough
      varicella infection for 4-year birth cohorts was 0.44% (244/55 317), and for each
      birth cohort was 0.95% (142/14 928), 0.44% (61/13 855), 0.22% (29/13 433) and
      0.09% (12/13 101), respectively. It was on the rise from 2008 to 2013 and the
      2007 birth cohort of it increased fastest from 0.04% (6/14 928) in 2007 to 0.32%
      (48/14 834) in 2013. The vaccine cumulative incidence of these who vaccinated 1
      dose varicella (the breakthrough varicella infection) was lower than these who
      were unvaccinated (the incidence: 6.25% (37/592), 3.52% (15/426), 3.69% (17/461)
      and 2.08% (8/384)) by each birth cohort (chi2= 130.27, P < 0.001 for 2007 birth
      cohort; chi2= 74.11, P < 0.001 for 2008 birth cohort; chi2= 162.80, P < 0.001 for
      2009 birth cohort; chi2= 100.01, P < 0.001 for 2010 birth cohort). The vaccine
      effectiveness for 4-year birth cohorts was 89.33% (95% CI: 86.7%-92.1%) and for
      each birth corhort was 84.78% (95% CI: 77.94%-89.50%), 86.82% (95% CI: 77.82%
      92.95%), 93.99% (95% CI: 89.27%-96.81%) and 95.60% (95% CI: 89.18%-98.21%),
      respectively. The effectiveness of each birth cohort declinedgradually from 2008
      to 2013 and the 2009 birth cohort of it decreased fastest from 98.86% in 2010 to
      66.83% in 2013. CONCLUSIONS: The 1-dose varicella vaccine effectiveness was good,
      but breakthrough varicella infection rate was on the rise with time and the VE
      declined gradually from 2008 to 2013.

PMID- 26310474
TI  - [Epidemiological characteristics of norovirus variant of GII.4 Sydney and the
      outbreaks caused by norovirus variant of GII.4 Sydney in Guangdong province, 2012
      2014].
AB  - OBJECTIVE: To analyze epidemiological characteristics of norovirus variant of
      GII.4 Sydney from January 2012 to June 2014 in sentinel hospitals of Guangdong
      province, as well as the outbreaks caused by norovirus variant of GII.4 Sydney.
      METHODS: During January 2012 to June 2014, a total of 10 750 fecal samples were
      obtained from 22 hospitals of surveillance sites in Guangdong province. Those
      samples were sent to the local municipal CDCs for extracting and detecting
      norovirus nucleic acid. Then, all the positive samples were delivered to
      Guangdong provincial CDC that used Random Number Method to draw 855 positive
      samples for norovirus genotyping, and 690 samples were successfully sequenced.
      Chi-square tests were used to compare norovirus infection status of diarrhea
      cases in different age groups as well as during different periods.
      Epidemiological data of 13 outbreaks which were caused by norovirus variant of
      GII.4 Sydney from January 2012 to June 2014 were collected from the Public Health
      Emergency Management Information System of Guangdong Province, and the
      epidemiological characteristics were analyzed. RESULTS: The norovirus variant of
      GII.4 Sydney was first detected in August 2012 and the detection rate was 13/15
      in November 2012. During November 2012 to January 2013 (period T1), the norovirus
      positive rate of each month was 23.8% (100/421), 15.9% (61/383) and 19.2%
      (95/495), respectively. During November 2013 to January 2014 (period T2), the
      norovirus positive rate of each month was 17.0% (90/529), 8.7% (37/426) and 11.2%
      (46/409), respectively which were significantly lower than that of period T1
      (chi2 alue was 6.65, 9.93 and 10.74. P value was 0.010, 0.002, and 0.001,
      respectively). In period T1, the norovirus positive rate of people ages 15 and
      older was 26.3% (143/543) and the rate of people under 15 was 14.9% (113/756)
      (chi2 = 2.90, P < 0.001). In period T2, the norovirus positive rate of people
      ages 15 and older was 10.1% (52/516) and the rate of people under 15 (14.3%
      (121/848)) (chi2= 5.09, P = 0.024). The foodborne transmission was the infection
      source for ten of thirteen outbreaks. CONCLUSION: The norovirus variant of GII.4
      Sydney was first detected in August 2012. The epidemic began to occur in the
      community since November 2012, and the strength of the epidemic declined 1 year
      later. The foodborne transmission was the main infection sources for the
      outbreaks caused by norovirus variant of GII.4 Sydney.

PMID- 26310475
TI  - [The burden of infectious disease and changing pattern from in 1990 and 2010,
      China].
AB  - OBJECTIVE: To investigate the burden of infectious disease of the Chinese
      population in 1990 and 2010 and changing pattern in the past 20 years. METHODS:
      Results of the Global Burden of Disease Study 2010 (GBD 2010) were used to
      demonstrate the burden of infectious disease of the Chinese population in 1990
      and 2010 and changing pattern from 1990 to 2010 by gender and age groups,
      including indicators of incidence, mortality, years of life lost due to premature
      mortality (YLL), years lived with disability (YLD), disability-adjusted life
      years (DALY), and their age-standardized rates using data of the 2010 National
      Census as a standard population. RESULTS: In 1990 incidence, standardized
      incidence rate, mortality, standardized mortality rate, DALY, standardized DALY
      rate, YLL, standardized YLL rate, YLD, and standardized YLD rate of infectious
      disease in China were 3 067 469 200 cases, 242 669.34 cases/100 000, 824 300
      cases, 72.27 cases/100 000, 58 937 700 person-years (PYRS), 3 992.85 PYRS/100
      000, 46 504 100 PYRS, 2 932.99 PYRS/100 000, 12 433 600 PYRS, and 1 059.86
      PYRS/100 000, respectively. All the aboved indicators were declined from 1990 to
      2010, in 2010 they were 3 065 985 800 cases, 224 351.66 cases/100 000, 388 600
      cases, 30.74 cases/100 000, 19 492 200 PYRS, 1 440.75 PYRS/100 000, 12 045 700
      PYRS, 891.87 PYRS/100 000, 7 446 500 PYRS, and 548.89 PYRS/100 000, respectively.
      When 2010's indicators were compared to those in 1990, the rates of increase of
      incidence, incidence rate, mortality, mortality rate, DALY, DALY rate, YLL, YLL
      rate, YLD, and YLD rate were 56.84%, -9.85%, -33.07%, -61.54%, -27.68%, -58.42%, 
      32.46%, -61.17%, -16.75%, and -52.13% for 50-69 age group; for >= 70 age group,
      57.90%, -5.86%, 7.41%, -36.12%, -5.00%, -43.51%, -5.14%, -43.59%, -4.52%, and 
      43.2%. CONCLUSIONS: The burden of infectious disease of the Chinese population
      was declined from 1990 to 2010; however, the incidence of infectious disease was
      increased in >= 50 age groups.

PMID- 26310476
TI  - [Analysis of factors associated with antiretroviral therapy intiation and its
      timeliness among HIV sero-discordant couples in high HIV prevalence regions,
      China].
AB  - OBJECTIVE: To analyze factors associated with antiretroviral therapy (ART)
      initiation and its timeliness among HIV sero-discordant couples in high HIV
      prevalence regions in China. METHODS: Data from the national HIV epidemiology and
      treatment databases by Dec 31, 2013 were used to collect HIV serodiscordant
      couples' baseline and follow-up informations in 40 counties which had reported
      200 HIV cases cumulatively from Yunnan, Guangxi, Sichuan, Henan, and Xinjiang.
      Positive couples were divided into ART group and Non-ART group based on their ART
      initiation status. Sero-discordant couples that were reported between January 1,
      2012 and October 31, 2013 and initiated ART treatment by 2013, were classified
      into two categories: 'having initiated ART within two months of receiving their
      HIV diagnosis', and not accessing timely treatment as 'having not initiated ART
      within two months of receiving their HIV diagnosis'. Multivariate logistic
      regressions were used to analyze potential factors associated with ART initiation
      and serodiscordant couples' timeliness to treatment. Odds ratios (95% confidence
      internal) were used to measure the associations. RESULTS: A total of 10 213 HIV
      positive individuals were included in this study, among whom 73.9% (7 550/10 213)
      were males and 26.1% (2 663/10 213) were females, 66.4% (6 780/10 213) had
      initiated ART and 33.6% (3 433/10 213) had not. There were 1 733 serodiscordant
      couples who were reported during January 1, 2012 to October 31, 2013 had
      initiated ART. Among those 64.9% (1 125/1 733) had successfully initiated ART
      within two months of receiving their HIV diagnosis and 35.1% (608/1 733) had not.
      Multivariate logistic regression analysis showed that those being male were
      0.81(0.71-0.92) less likely to initiate ART, as compared with those being female.
      Those being Yi ethnicity were 0.29(0.25-0.35) less likely to initiate ART, as
      compared with those being Han ethnicity. Those being Uygur ethnicity were 1.57
      (1.28-1.93) times more likely to initiate ART, as compared with those being Han
      ethnicity. Those engaging the other jobs were 0.85(0.75-0.96) less likely to
      initiate ART, as compared with those being peasant. Those being diagnosed in
      medical institutions were 0.61 (0.53-0.71) less likely to initiate ART, as
      compared with those being diagnosed in VCT. Those having CD4+ T cells of 250-349,
      350-550 and > 550 were 0.75 (0.64-0.89), 0.17 (0.14-0.19), 0.10 (0.08-0.11) less
      likely to initiate ART, respectively, as compared with those having CD4+ T cells
      of < 250. Those having duration of follow-up of 13-36 months and >= 37 months
      were 0.55(0.48-0.63) and 0.32 (0.28-0.37) less likely to initiate ART
      respectively, as compared with those having duration of follow-up of <= 12
      months. Multivariate logistic regression analysis showed that those being Yi and
      Uygur ethnicity were 0.63 (0.44-0.91) and 0.40(0.29-0.56) less likely to initiate
      ART timely respectively, as compared with those being Han ethnicity. Those being
      infected through injecting drug use were 0.64 (0.47-0.86) less likely to initiate
      ART timely, as compared with those being infected through heterosexual
      intercourse. Those being diagnosed in other institutions were 0.58(0.43-0.78)
      less likely to initiate ART timely, as compared with those being diagnosed in
      VCT. Those having CD4+T cells of 250-349, 350-550 and > 550 were 0.75(0.56-1.00),
      0.44(0.34-0.58), and 0.31(0.22-0.45) less likely to initiate ART timely
      respectively, as compared with those having CD4+ T cells of < 250. CONCLUSION:
      Being males, being Yi ethnicity, engaging other jobs, being diagnosed in medical
      institutions, having high CD4+ T cells and having long duration of follow-up were
      risk factors for initiating ART among serodiscordant couples.Being Yi and Uygur
      ethnicity, being infected through injecting drug use, and having CD4+ T cells
      were risk factors for initiating ART timely among serodiscordant couples.

PMID- 26310477
TI  - [Impact on prevalence of schitosomiasis after runs of Three Gorges Reservoir
      Project in the section of Anhui province].
AB  - OBJECTIVE: To investigate the changes of water level and the distribution of
      snails in Anhui province before and after runs of the Three Gorges Reservoir
      Project, and to determine the relationship between the two factors and
      schistosomiasis transmission. METHODS: The hydrologic data of Datong hydrologic
      station and the data of snail status and schistosomiasis morbidity in Anhui
      Province were collected. The data from 1991 to 2002 and 2003 to 2012 were
      considered as before and after the impoundment of the Three Gorges Reservoir
      Project. Based on the prevalence of schistosomiasis, the cases of people and
      cattle were speculated, and the average infection rate of people and cattle were
      calculated. The t-test was used to compare the difference of snail area and the
      density of living snails before and after the impoundment of the Three Gorges
      Project. The pearson method was used to analyze the relationship between water
      level and snail area. The spearman method was used to analyze the relationship
      between the water level and the distribution of snails. RESULTS: From 1991 to
      2012, the range of the highest water level, the lowest water level, the
      difference between the highest and lowest water level, the mean in the abundant
      water seasons, the mean in the dry water seasons, and the difference between the
      abundant water seasons and the dry water seasons was 11.40-16.30, 3.68-5.20, 6.70
      12.12, 9.92-14.40, 4.77-7.64 and 4.13-8.93 m, respectively. The snail areas was
      (28 613 +/- 362) hm2 and (29 477 +/- 918) hm2 (t = -3.00, P = 0.007), the density
      of living snails was 1.51 (1.15-2.43) and 0.43 (0.29-1.10) snails/0.11 m2 (H =
      4.28, P < 0.001) before and after the impoundment of the Three Gorges Project,
      respectively. The average infection rate of people and cattle was 1.68% (99 482/5
      935 147) and 4.62% (13 923/3 011 33), and the average number of acute
      schistosomiasis cases was 328, before the impoundment of the Three Gorges
      Project; 0.60% (39 747/6 649 380), 1.65% (1 291/783 224) and 71 after the
      impoundment of the Three Gorges Reservoir Project, respectively. The snail areas
      had negative correlation with the highest water level, the difference between the
      highest and lowest water level, the mean in the abundant water seasons (r value
      was -0.514, -0.509 and -0.477; P value was 0.014, 0.015 and 0.025, respectively).
      The infection rate of people had positive correlation with the highest water
      level, the difference between the highest and lowest water level, the mean in the
      abundant water seasons (r value was 0.532, 0.587 and 0.446; P value was 0.011,
      0.004 and 0.038, respectively). The infection rate of cattle had positive
      correlation with the highest water level, the difference between the highest and
      lowest water level (r value was 0.507 and 0.553; P value was 0.016 and 0.008,
      respectively). The number of acute schistosomiasis cases had positive correlation
      with the highest water level, the difference between the highest and lowest water
      level (r value was 0.481 and 0.486; P value was 0.023 and 0.022, respectively).
      CONCLUSION: Following the runs of the Three Gorges Reservoir Project, the change
      of water level in the section of Anhui Province affected the distribution of
      snails and the infection of people and cattle to some extent. The snail areas
      showed an upward trend, and the density of living snails, the infection rate of
      people and cattle showed a downward trend. The runs of Three Gorges Reservoir
      Project has certain role to reduce flood and helpful for schistosomiasis control.

PMID- 26310478
TI  - [Long-term effect of cadmium exposure on residents' renal dysfunction: An
      epidemiologic study].
AB  - OBJECTIVE: To study long-term effect on renal function exposed to environmental
      cadmium. METHODS: Stratified random sampling and cluster sampling method of
      epidemiological investigations were carried out in northern Guangdong province
      between April, 2011 and August, 2012. A total of 167 residents who lived in high
      cadmium exposure area for more than 15 years, aged above 40 were selected in
      exposed group. Moreover, A total of 145 residents who had similar living and
      economic conditions and lived in local for more than 15 years, aged above 40 were
      selected in control group. We used health questionnaires and medical examinations
      in order to acquire their health status. Home-harvested rice and vegetables were
      collected using quartering method for detection of cadmium level. Urine specimens
      of residents were collected for detection of cadmium level and creatinine as well
      as renal dysfunction biomarkers, namely, N-acetyl-beta-D-glucosamidase (NAG),
      beta2-microglobulin (beta2-MG), and retinol binding protein(RBP), respectively.
      The analysis of spearman rank correlation and multiple regression were used to
      investigate the relationships between age, urinary cadmium levels and renal
      injury biomarkers. RESULTS: The cadmium levels in rice and vegetables of exposed
      group were 0.75 and 0.10 mg/kg, both were significantly higher than 0.07 and 0.01
      mg/kg in the control group (Z values were -6.32 and -7.84, all P values < 0.001).
      The urinary cadmium level of exposed group was 8.29 ug/g . cr, which was higher
      than that of the control group 2.03 ug/g . cr with significant difference (Z
      value was -11.39, P < 0.001). After stratified the total population by age, the
      urinary cadmium level in 40-49 years, 50-59 years and >= 60 years subgroups were
      7.22, 8.71, and 13.10 ug/g . cr, which both were significantly higher than 1.80,
      2.04, and 2.05 ug/g . cr in the control group (Z values were -5.22, -7.41, and 
      7.14, all P values < 0.001). After stratified the total population by gender, the
      urinary cadmium level of male and female were 5.12 and 12.36 ug/g . cr, which
      both were significantly higher than 1.79 and 2.16 ug/g . cr in the control group
      (Z values were -7.68 and -9.03, all P values < 0.001). Comparing the differences
      of renal dysfunction biomarkers (NAG, beta2-MG, RBP) between two groups. The
      level of urinary beta2-MG and RBP of exposed group were 0.21 and 0.04 ug/g . cr,
      which were higher than 0.05 and 0.00 ug/g . cr of the control group with
      significant difference (Z value was -7.08 and -9.65, all P values < 0.001).
      Pearson correlation analysis showed that NAG, beta2-MG and RBP were positively
      correlated with urinary cadmium and age, the correlation coefficients were 0.57,
      0.49, 0.21 and 0.22, 0.26, 0.23 respectively (all P values < 0.001). After
      adjusting the effect of age, it was appeared that urinary cadmium levels
      contributed most to the alteration of NAG, beta2-MG and RBP, the standardized
      regression coefficients were 0.57, 0.49 and 0.20 (all P values < 0.001), and
      suggested that the cadmium body burden was one of the most important factors for
      renal dysfunction. CONCLUSION: Residents, who had cadmium contaminated rice and
      vegetables for a long time, would take the risk of increasing body burden of
      cadmium and urinary early biomarkers of renal tubular injury that referred to
      occurrence of renal dysfunction.

PMID- 26310479
TI  - [Relationship between environmental tobacco smoke and lung cancer risk among
      nonsmokers in China: A meta-analysis].
AB  - OBJECTIVE: To investigate the relationship between the environmental tobacco
      smoke (ETS) and lung cancer by Meta-analysis. METHODS: We used "lung cancer/lung
      neoplasm", "non-smoking/non-smoker", "China/Chinese", "case-control/case
      control", "risk factor", "environmental tobacco smoke/passive smoking" as key
      words, to search papers in databases including Chinese BioMedical Literature
      (CBM), China National Knowledge Internet (CNKI), Wanfang, Vip Citation Databases
      (VIP), PubMed and Web of Science databases, and collected the case-control
      studies on ETS and lung cancer among Chinese non-smokers from January 1999 to
      December 2013. A total of 129 research papers were collected. RevMan 5.2 software
      was used to calculate combined odds radio (OR) and 95% CI. RESULTS: Qualified 18
      literatures were included, total cases 6 145 and controls 8 132. Consolidated
      results showed that ETS exposure could increase the risk of lung cancer, combined
      OR (95% CI) = 1.52 (1.42-1.64). Stratified analysis showed that ETS exposure was
      found to be significantly associated with an increasing risk of the lung cancer
      on non-smoking women and men, and combined OR (95% CI) were 1.58 (1.42-1.75) and
      1.34 (1.08-1.65), respectively; the ETS exposure from family or the working
      environment could increase the risk of lung cancer, and combined OR (95% CI) were
      1.48 (1.20-1.82) and 1.38 (1.13-1.69) respectively; childhood exposure and adult
      exposure were no significant statistical significance, and combined OR (95% CI)
      were 1.37 (0.98-1.91), and 1.34 (0.97-1.85) respectively. CONCLUSION:
      Environmental tobacco smoke exposure was a significant risk factor of lung cancer
      among non-smokers in China.

PMID- 26310480
TI  - [A meta-analysis of body mass index and the risk of lung cancer in the Chinese
      population].
AB  - OBJECTIVE: To investigate the association between obesity and the risk of lung
      cancer and evaluate a dose-response relationship between body mass index (BMI)
      and incidence risk of lung cancer in the Chinese population. METHODS: A
      systematic literature search for BMI and incidence risk of lung cancer in the
      Chinese population, as well as through the reference lists of retrieved articles.
      The literature databases including Chinese National Knowledge Infrastructure,
      Wanfang, PubMed, Embase and Google Scholar. Time range was from the founding of
      each database to September 2014 and a total of 93 research papers were collected.
      Meta-analysis was conducted to calculate pooled odds ratio and corresponding 95%
      CI. Generalized least-squares regression methods were used to make a dose
      response meta-analysis between BMI and incidence risk of lung cancer. RESULTS:
      Seven studies were included in the meta-analysis, with a number of 2 351 lung
      cancer cases. Results showed that obesity was inversely associated with lung
      cancer incidence (OR = 0.68, 95% CI: 0.59-0.79) (heterogeneity test: I2 = 0, P =
      0.594). The association did not change with stratification by study design, sex,
      smoking status, BMI measurement method and study population. A linear dose
      response association between BMI and risk of lung cancer was visually
      significant, and lung cancer risk would be reduced 21% for per 5 kg/m2 BMI
      increase (OR = 0.79, 95% CI: 0.71-0.89) (heterogeneity test: q = 22.43, P =
      0.002). CONCLUSION: The results of this meta-analysis indicated that higher BMI
      was a protective factor against lung cancer, but smoking may play a stronger role
      as a confounding factor for the most important role with lung cancer incidence.

PMID- 26310481
TI  - [The study of the exposure time of the pneumoconiosis and the outcome of
      suspected pneumoconiosis in Qingpu district of Shanghai in 2002-2013].

PMID- 26310482
TI  - [Analysis on epidemiology of pneumoconiosis disease in Urumqi, 1994-2013].

PMID- 26310483
TI  - [Advance in application of syndromic surveillance for detection of emerging
      infectious diseases and outbreak alerts].
AB  - Over the past decade, syndromic surveillance, as supplementation of disease
      surveillance, has provided possibility of early alert in a real-time way for
      detection of emerging infectious diseases and outbreaks of widespread infectious
      diseases, resulting in improvement in sensitivity of outbreak detection and
      public health alert capacity. This tool has been highly valued and widely used in
      the world, and effective implementation has been observed in China. Upon abundant
      literature search, the authors reviewed the progress and advance of syndromic
      surveillance in early alert of emerging infectious diseases and outbreaks, and
      analyzed the problem met in the current situation in China when implementing
      syndromic surveillance in local facilities, which are high cost, lack of medical
      information platform, lack of real-time digital alert system and lack of a
      comprehensive information exchange platform. The authors suggested that syndromic
      surveillance should be implemented considering the local situation and performed
      in a more effective way in the current situation. Syndromic surveillance has to
      be integrated into the conventional public health surveillance systems and
      advanced laboratory networks. Digital information system is urgently needed to
      achieve real-time alert. 

PMID- 26310484
TI  - [Research on exposure to polycyclic aromatic hydrocarbons during pregnancy and
      risk of preterm birth].
AB  - Polycyclic aromatic hydrocarbons (PAH) are a group of toxic pollutants existing
      in the environment widely, and can be taken into the body through various ways
      containing the digestive tract, respiratory tract and so on. Pregnant women and
      newborn infants are important and susceptive populations. Relevant study
      evidences indicate that exposure to PAH during pregnancy may be a important risk
      factor of preterm delivery, but the special mechanism isn't very clear and may be
      related with DNA damage, oxidative stress, systemic inflammation, endocrine
      disruption and so on. This paper reviewed related contents including the
      influences and evaluation methods of exposure to PAH during pregnancy, increasing
      risk and potential mechanism for preterm delivery of exposure to PAH during
      pregnancy. 

PMID- 26310485
TI  - YangZheng XiaoJi exerts anti-tumour growth effects by antagonising the effects of
      HGF and its receptor, cMET, in human lung cancer cells.
AB  - BACKGROUND: Hepatocyte growth factor (HGF) is a cytokine that has a profound
      effect on cancer cells by stimulating migration and invasion and acting as an
      angiogenic factor. In lung cancer, the factor also plays a pivotal role and is
      linked to a poor outcome in patients. In particular, HGF is known to work in
      combination with EGF on lung cancer cells. In the present study, we investigated
      the effect of a traditional Chinese medicine reported in cancer therapies, namely
      YangZheng XiaoJi (YZXJ) on lung cancer and on HGF mediated migration and invasion
      of lung cancer cells. METHODS: Human lung cancer cells, SKMES1 and A549 were used
      in the study. An extract from the medicine was used. Cell migration was
      investigated using the EVOS and by ECIS. Cell-matrix adhesion and in vitro
      invasion were assessed. In vivo growth of lung cancer was tested using an in vivo
      xenograft tumour model and activation of the HGF receptor in lung tumours by an
      immunofluorescence method. RESULTS: Both lung cancer cells increased their
      migration in response to HGF and responded to YZXJ by reducing their speed of
      migration. YZXJ markedly reduced the migration and in vitro invasiveness induced
      by HGF. It worked synergistically with PHA665752 and SU11274, HGF receptor
      inhibitors on the lung cancer cells both on HGF receptor activation and on cell
      functions. A combination of HGF and EGF resulted in a greater increase in cell
      migration, which was similarly inhibited by YZXJ, and in combination with the HGF
      receptor and EGF receptor inhibitors. In vivo, YZXJ reduced the rate of tumour
      growth and potentiated the effects of PHA665752 on tumour growth. It was further
      revealed that YZXJ significantly reduced the degree of phosphorylation of the HGF
      receptor in lung tumours. CONCLUSION: YZXJ has a significant role in reducing the
      migration, invasion and in vivo tumour growth of lung cancer and acts to inhibit
      the migratory and invasive effects induced by HGF and indeed by HGF/EGF. This
      effect is likely attributed to the inhibition of the HGF receptor activation.
      These results indicate that YZXJ has a therapeutic role in lung cancer and that
      combined strategy with methods to block HGF and EGF should be considered.

PMID- 26310486
TI  - The 100 most-cited articles on cardiovascular diseases from Mainland China.
AB  - BACKGROUND: China, as a rapidly developing country with the largest population of
      cardiologist in the world, has an increasing importance in the field of
      cardiology. However, the quantity and quality of research production in the field
      of cardiology is unclear. AIMS: To analyze the characteristics of the high-level
      articles published on cardiovascular diseases in Mainland China, and to provide
      information about achievements and development in cardiovascular research.
      METHODS: We searched the Science Citation Index Expanded for citations of
      cardiovascular articles originating in mainland China from 2004 to 2015. For the
      100 most frequently cited articles (T100), we evaluated the number of citations,
      publication time, province of origin, journal, impact factor, topic or
      subspecialty of the research, and publication type. RESULTS: The most frequently
      cited article received 703 citations at the most, while 50 at the least (mean
      91.6 citations per article). T100 originated from 16 provinces, the plurality (n
      = 34) being from the Beijing. Sixty-seven percent were published during 2006
      2009. The publications were in 29 different journals of which Circulation
      published the most (n = 14). Leading general medical journals Journal of the
      American Medical Association (n = 1), Lancet (n = 0) and New England Journal of
      Medicine (n = 0) featured only 1 published article, despite their extremely high
      impact factors. Of the T100 articles, there were 50 basic researches, 44 clinical
      researches, 5 meta-analyses and 1 review article. Clinical researches had the
      highest mean citations (mean 102.6 citations per article). CONCLUSIONS: This
      study provides a historical perspective on the scientific progress, and the
      trends in cardiovascular medicine in Mainland China.

PMID- 26310487
TI  - Mutation analysis of the genes associated with anterior segment dysgenesis,
      microcornea and microphthalmia in 257 patients with glaucoma.
AB  - Genetic factors have an important role in the development of glaucoma; however,
      the exact genetic defects remain to be identified in the majority of patients.
      Glaucoma is frequently observed in patients with anterior segment dysgenesis
      (ASD), microcornea or microphthalmia. The present study aimed to detect the
      potential mutations in the genes associated with ASD, microcornea and
      microphthalmia in 257 patients with glaucoma. Variants in 43 of the 46 genes,
      which are associated with ASD, microcornea or microphthalmia, were available in
      whole-exome sequencing. Candidate variants in the 43 genes were selected
      following multi-step bioinformatic analysis and were subsequently confirmed by
      Sanger sequencing. Confirmed variants were further validated by segregation
      analysis and analysis of controls. Overall, 70 candidate variants were selected
      from whole-exome sequencing, of which 53 (75.7%) were confirmed by Sanger
      sequencing. In total, 27 of the 53 were considered potentially pathogenic based
      on bioinformatic analysis and analysis of controls. Of the 27, 6 were identified
      in BEST1, 4 in EYA1, 3 in GDF6, 2 in BMP4, 2 in CRYBA4, 2 in HCCS, and 1 in each
      of CRYAA, CRYGC, CRYGD, COL4A1, FOXC1, GJA8, PITX2 and SHH. The 27 variants were
      detected in 28 of 257 (10.9%) patients, including 11 of 125 patients with primary
      open-angle glaucoma and 17 of 132 patients with primary angle-closure glaucoma.
      Variants in these genes may be a potential risk factor for primary glaucoma.
      Careful clinical observation and analysis of additional patients in different
      populations are expected to further these findings. 

PMID- 26310488
TI  - MRI for discriminating metastatic ovarian tumors from primary epithelial ovarian
      cancers.
AB  - AIMS: To find specific magnetic resonance imaging (MRI) features to differentiate
      metastatic ovarian tumors from primary epithelial ovarian cancers. METHODS:
      Eleven cases with metastatic ovarian tumors and 26 cases with primary malignant
      epithelial ovarian cancers were retrospectively studied. All features such as
      patient characteristics, MRI findings and biomarkers were evaluated. The
      differences including laterality, configuration, uniformity of locules, diffusion
      weighted imaging (DWI) signal of solid components and enhancement of solid
      portions between metastatic ovarian tumors and primary epithelial ovarian cancers
      were compared by Fisher's exact test. Median age of patients, the maximum
      diameter of lesions and biomarkers were compared by the Mann-Whitney test.
      RESULTS: Patients with metastatic ovarian tumors were younger than patients with
      primary epithelial ovarian cancers in the median age (P = 0.015). Patients with
      bilateral tumors in metastatic ovarian tumors were more than those of primary
      epithelial ovarian cancers (P = 0.032). The maximum diameter of lesions in
      metastatic ovarian tumors was smaller than that of primary epithelial ovarian
      cancers (P = 0.005). The locules in metastatic ovarian tumors were more uniform
      than those of primary epithelial ovarian cancers (P = 0.024). The enhancement of
      solid portions in metastatic ovarian tumors showed more moderate than that of
      primary epithelial ovarian cancers (P = 0.037). There was no statistically
      significant difference between the two groups in configuration, DWI signal of
      solid components and ascites. Biomarkers such as CA125 and human epididymis
      protein 4 (HE4) in metastatic ovarian tumors showed less elevated than that of
      primary epithelial ovarian cancers. CONCLUSIONS: Significant differences between
      metastatic ovarian tumors and primary epithelial ovarian cancers were found in
      the median age of patients, laterality, the maximum diameter of lesions,
      uniformity of locules, enhancement patterns of solid portions and biomarkers.
      Metastatic ovarian tumors usually presented in the younger patients, smaller
      sized, more bilateral lesions, more uniform of locules, more moderate enhancement
      of solid portions, and less elevated levels of CA125 and HE4 than those of
      primary epithelial ovarian cancers.

PMID- 26310489
TI  - Correlations between female breast density and biochemical markers.
AB  - [Purpose] The aim of this study was to identify biochemical markers related to
      breast density. The study was performed with 200 patients who received
      mammography and biochemical marker testing between March 1, 2014 to October 1,
      2014. [Subjects and Methods] Following the American College of Radiology, Breast
      Imaging Reporting and Data System (ACR BI-RADS), breast parenchymal pattern
      density from mammography was categorized into four grades: grade 1, almost
      entirely fat; grade 2, fibroglandular densities; grade 3, heterogeneously dense;
      and grade 4, extremely dense. Regarding biochemical markers, subjects underwent
      blood and urine tests after a 12-h fast. We analyzed correlations among breast
      density, general characteristics, and biochemical markers. [Results] Breast
      density-related factors were age, height, weight, body mass index (BMI),
      hematocrit, MCH, RDW, AST, ALT, ALP, uric acid, gammaGT, triglycerides, total
      cholesterol, HDL-cholesterol, and LDL-cholesterol. [Conclusion] The results can
      be used as basic and comparative data for the prevention and early control of
      breast cancer. 

PMID- 26310490
TI  - Optimising utilisation of kidneys from very young deceased donors: the technique
      of en bloc kidney transplantation.
AB  - Kidneys of paediatric deceased donors were previously considered suboptimal for
      older recipients. An 18-month-old deceased donor was made available via
      Singapore's Medical (Therapy, Education and Research) Act. To the best of our
      knowledge, she is the youngest local donor. We herein report a case of successful
      kidney transplantation, using the en bloc technique, to a 15-year-old girl with
      renal failure secondary to bilateral cystic dysplastic kidney. 

PMID- 26310491
TI  - A crystalline low molecular weight cyclic organoboron compound for efficient
      solid state lithium ion transport.
AB  - We report the synthesis of a crystalline cyclic organoboron compound that shows
      an anomalous Li-ion conduction behaviour with specific composition and method of
      insertion of a Li salt. The enhanced ionic conductivity of crystalline boric
      ester/LiTFSI prepared by the grinding method should be due to the formation of
      regulated ion-conduction channels scaffolded by boron-anion interaction. 

PMID- 26310492
TI  - A tree-like Bayesian structure learning algorithm for small-sample datasets from
      complex biological model systems.
AB  - BACKGROUND: There are increasing efforts to bring high-throughput systems biology
      techniques to bear on complex animal model systems, often with a goal of learning
      about underlying regulatory network structures (e.g., gene regulatory networks).
      However, complex animal model systems typically have significant limitations on
      cohort sizes, number of samples, and the ability to perform follow-up and
      validation experiments. These constraints are particularly problematic for many
      current network learning approaches, which require large numbers of samples and
      may predict many more regulatory relationships than actually exist. RESULTS:
      Here, we test the idea that by leveraging the accuracy and efficiency of
      classifiers, we can construct high-quality networks that capture important
      interactions between variables in datasets with few samples. We start from a
      previously-developed tree-like Bayesian classifier and generalize its network
      learning approach to allow for arbitrary depth and complexity of tree-like
      networks. Using four diverse sample networks, we demonstrate that this approach
      performs consistently better at low sample sizes than the Sparse Candidate
      Algorithm, a representative approach for comparison because it is known to
      generate Bayesian networks with high positive predictive value. We develop and
      demonstrate a resampling-based approach to enable the identification of a viable
      root for the learned tree-like network, important for cases where the root of a
      network is not known a priori. We also develop and demonstrate an integrated
      resampling-based approach to the reduction of variable space for the learning of
      the network. Finally, we demonstrate the utility of this approach via the
      analysis of a transcriptional dataset of a malaria challenge in a non-human
      primate model system, Macaca mulatta, suggesting the potential to capture
      indicators of the earliest stages of cellular differentiation during
      leukopoiesis. CONCLUSIONS: We demonstrate that by starting from effective and
      efficient approaches for creating classifiers, we can identify interesting tree
      like network structures with significant ability to capture the relationships in
      the training data. This approach represents a promising strategy for inferring
      networks with high positive predictive value under the constraint of small
      numbers of samples, meeting a need that will only continue to grow as more high
      throughput studies are applied to complex model systems.

PMID- 26310493
TI  - Interleukin-1 Receptor-Associated Kinase 1/4 as a Novel Target for Inhibiting
      Neointimal Formation After Carotid Balloon Injury.
AB  - AIM: Interleukin-1 receptor-associated kinase 1 (IRAK1) and IRAK4 play essential
      roles in the induction of inflammatory gene products. We aimed to investigate the
      effect of the inhibition of IRAK1 and IRAK4 kinase activities on neointimal
      formation in rats with carotid artery balloon injuries using the IRAK1/4
      inhibitor N-(2-Morpholinylethyl)-2-(3-nitrobenzoylamido)-benzimidazole, a cell
      permeable benzimidazole compound. METHODS: Wistar rats and vascular smooth muscle
      cells (VSMCs) isolated from the thoracic aortas were used. Toll-like receptor 4
      (TLR4)-mediated nuclear factor kappa B (NFkappaB) signaling pathway was revealed
      by microarrays analysis. In addition, the differential expression of the TLR4
      pathway genes, including TLR4, IRAK1, IkappaBalpha, and interleukin-1beta (IL
      1beta), was confirmed by quantitative real-time polymerase chain reaction.
      Immunohistochemical staining, elastic-van Gieson and Masson staining, 5-ethynyl
      2'-deoxyuridine staining, enzyme-linked immunosorbent assay, transwell migration
      assay and western blotting were also contributed for relevant detection. RESULTS:
      The expression of TLR4 protein gradually increased at days 1, 3, 7, and 21 after
      balloon injury compared with the uninjured group. The dual inhibition of IRAK1
      and IRAK4 attenuated neointimal formation and fibrotic remodeling after injury in
      vivo and suppressed VSMC proliferation and migration in vitro. The production of
      mediators such as tumor necrosis factor-alpha and IL-1beta in injured arteries
      were also reduced by the inhibition of IRAK1 and IRAK4. The expression of
      NFkappaB p65- and F4/80-positive cells in inhibitor rats were fewer than those in
      control rats at day 7, while IRAK1 expression was markedly higher at day 3 in
      inhibitor rats. Furthermore, western blotting analysis revealed that the IRAK1/4
      inhibitor suppressed the IRAK1 and IRAK4 kinase activities and the activation of
      the TLR4-mediated NFkappaB pathway in vivo and in vitro. CONCLUSIONS: This study
      suggested that IRAK1/4 could serve as a potential therapeutic target to suppress
      neointimal formation in carotid arteries after balloon injury through the
      TLR4/NFkappaB signaling pathway.

PMID- 26310494
TI  - Measuring Procedure and Maximal Hyperemia in the Assessment of Fractional Flow
      Reserve for Superficial Femoral Artery Disease.
AB  - AIM: The optimal fractional flow reserve (FFR) measurement method for superficial
      femoral artery (SFA) lesions remains to be established. We clarified the optimal
      measuring procedure for FFR for SFA lesions and investigated the necessary dose
      of papaverine for inducing maximal hyperemia in SFA lesions. METHODS: Forty-eight
      patients with SFA lesions who underwent measurement of peripheral FFR (pFFR:
      distal mean pressure divided by proximal mean pressure) after endovascular
      treatment by the contralateral femoral crossover approach were prospectively
      enrolled. In the pFFR measurement, a guide sheath was placed on top of the common
      iliac bifurcation and pressure equalization was performed. After advancing the
      pressure wire distal to the SFA lesion, sequential papaverine administration
      selectively to the affected common iliac artery was performed. RESULTS: There
      were no symptoms, electrocardiogram changes, and significant pressure drops at
      the guide sheath tip with increasing papaverine dose. pFFR changes following 20,
      30, and 40 mg of papaverine were 0.87+/-0.10, 0.84+/-0.10, and 0.84+/-0.10,
      respectively (P<0.001). Although not significantly different, pFFR decreased more
      in several patients at 30 mg of papaverine than at 20 mg. The pFFR at 40 mg of
      papaverine was almost similar to that at 30 mg of papaverine. The necessary
      papaverine dose was not changed according to sex and number of run-off vessels.
      CONCLUSIONS: The contralateral femoral crossover approach is useful in FFR
      measurement for SFA lesions, and maximal hyperemia is induced by 30 mg of
      papaverine.

PMID- 26310495
TI  - Profound hypotony maculopathy in a first episode of bilateral idiopathic acute
      anterior uveitis.
AB  - BACKGROUND: We report a case of a HLA-B27 negative patient presenting with
      severe, bilateral, idiopathic acute anterior uveitis with acute hypotony and
      hypotony maculopathy as their first uveitic episode. CASE PRESENTATION: Within a
      week of onset of her first episode of acute anterior uveitis, a 45 year-old
      Caucasian lady developed profound ocular hypotony with unrecordable intraocular
      pressures, reduced vision and choroidal folds. All investigations were negative.
      Uveitic hypotony responded slowly to corticosteroids--intravenous, oral and
      topical--with normalization of intraocular pressure and resolution of choroidal
      folds after two months. Anterior uveitis and hypotony have not returned with six
      months of follow-up. CONCLUSION: Bilateral, profound hypotony maculopathy may
      present acutely in idiopathic acute anterior uveitis, may be slow to respond to
      treatment and should be considered as a cause of vision loss in patients with
      this condition.

PMID- 26310496
TI  - Optimizing immunosuppression: who can do more with less?

PMID- 26310497
TI  - Providing context to the implementation of health promoting schools: A case
      study.
AB  - PURPOSE: Issues related to program context are important components of population
      health interventions and particularly among complex, adaptive initiatives in
      schools. Health Promoting Schools (HPS) is a global approach to support early
      development of healthy behaviors among children and youth. The purpose of this
      study was to explicate the practical and contextual processes that influenced
      implementation of HPS in schools in Nova Scotia (Canada). METHODS: Using a case
      study approach, data was collected using interviews (n=14) with principals,
      teachers and parents, observations collected during school visits and document
      review in five diverse schools. RESULTS: Case study schools reported a variety of
      HPS practices and three key themes emerged that provided context to the processes
      that facilitated their implementation. The results suggest that although school
      characteristics (theme 1), like staff allocation, physical location and
      resources, are important, these barriers can be mitigated by building
      organizational capacity (theme 2) and establishing a supportive school community
      culture (theme 3). CONCLUSIONS: The study provided insight to the variability in
      implementation by describing how contextual barriers were experienced and
      mitigated by schools. Establishing a broad system to support HPS, with
      collaboration across health and education sectors, could help to progress
      adoption, implementation and sustainability of HPS.

PMID- 26310498
TI  - Matching study areas using Google Street View: A new application for an emerging
      technology.
AB  - Google Street View (GSV) can be used as an effective tool to conduct virtual
      neighborhood audits. We expand on this research by exploring the utility of a GSV
      based neighborhood audit to measure and match target and comparison study areas.
      We developed a GSV-based inventory to measure characteristics of retail alcohol
      stores and their surrounding neighborhoods. We assessed its reliability and
      assessed the utility of GSV-based audits for matching target and comparison study
      areas. We found that GSV-based neighborhood audits can be a useful, reliable, and
      cost-effective tool for matching target and comparison study areas when archival
      data are insufficient and primary data collection is prohibitive. We suggest that
      researchers focus on characteristics that are easily visible on GSV and are
      relatively stable over time when creating future GSV-based measuring and matching
      tools. Dividing the study area into small segments may also provide more accurate
      measurements and more precise matching. 

PMID- 26310499
TI  - Folding and binding energy of a calmodulin-binding cell antiproliferative
      peptide.
AB  - We carry out a computational study of a calmodulin-binding peptide shown to be
      effective in reducing cell proliferation. We find several folded states for two
      short variants of different length of the peptide and determine the location of
      the binding site on calmodulin, the binding free energy for the different
      conformers and structural details that play a role in optimal binding. Binding to
      a hydrophobic pocket in calmodulin occurs via an anchoring phenylalanine residue
      of the natively disordered peptide, and is enhanced when a neighbouring
      hydrophobic residue acts as a co-anchor. The shorter sequence possesses better
      binding to calmodulin, which is encouraging in terms of the development of non
      peptide analogues as therapeutic agents. 

PMID- 26310500
TI  - Changes in Payer Mix and Physician Reimbursement After the Affordable Care Act
      and Medicaid Expansion.
AB  - Although uncompensated care for hospital-based care has fallen dramatically since
      the implementation of the Affordable Care Act and Medicaid expansion, the changes
      in hospital physician reimbursement are not known. We evaluated if payer mix and
      physician reimbursement by encounter changed between 2013 and 2014 in an academic
      hospitalist practice in a Medicaid expansion state. This was a retrospective
      cohort study of all general medicine inpatient admissions to an academic
      hospitalist group in 2013 and 2014. The proportion of encounters by payer and
      reimbursement/inpatient encounter were compared in 2013 versus 2014. A
      sensitivity analysis determined the relative contribution of different factors to
      the change in reimbursement/encounter. Among 37 540 and 40 397 general medicine
      inpatient encounters in 2013 and 2014, respectively, Medicaid encounters
      increased (17.3% to 30.0%, P < .001), uninsured encounters decreased (18.4% to
      6.3%, P < 0.001), and private payer encounters also decreased (14.1% to 13.3%, P
      = .001). The median reimbursement/encounter increased 4.2% from $79.98/encounter
      in 2013 to $83.36/encounter in 2014 (P < .001). In a sensitivity analysis,
      changes in length of stay, proportions in encounter type by payer, payer mix, and
      reimbursement for encounter type by payer accounted for -0.7%, 0.8%, 2.0%, and
      2.3% of the reimbursement change, respectively. From 2013 to 2014, Medicaid
      encounters increased, and uninsured and private payer encounters decreased within
      our hospitalist practice. Reimbursement/encounter also increased, much of which
      could be attributed to a change in payer mix. Further analyses of physician
      reimbursement in Medicaid expansion and non-expansion states would further
      delineate reimbursement changes that are directly attributable to Medicaid
      expansion.

PMID- 26310501
TI  - More Health Expenditure, Better Economic Performance? Empirical Evidence From
      OECD Countries.
AB  - Recent economic downturns have led many countries to reduce health spending
      dramatically, with the World Health Organization raising concerns over the
      effects of this, in particular among the poor and vulnerable. With the provision
      of appropriate health care, the population of a country could have better health,
      thus strengthening the nation's human capital, which could contribute to economic
      growth through improved productivity. How much should countries spend on health
      care? This study aims to estimate the optimal health care expenditure in a
      growing economy. Applying the experiences of countries from the Organization for
      Economic Co-Operation and Development (OECD) over the period 1990 to 2009, this
      research introduces the method of system generalized method of moments (GMM) to
      derive the design of the estimators of the focal variables. Empirical evidence
      indicates that when the ratio of health spending to gross domestic product (GDP)
      is less than the optimal level of 7.55%, increases in health spending effectively
      lead to better economic performance. Above this, more spending does not equate to
      better care. The real level of health spending in OECD countries is 5.48% of GDP,
      with a 1.87% economic growth rate. The question which is posed by this study is a
      pertinent one, especially in the current context of financially constrained
      health systems around the world. The analytical results of this work will allow
      policymakers to better allocate scarce resources to achieve their macroeconomic
      goals. 

PMID- 26310502
TI  - An approach to plan and evaluate the location of radiotherapy services and its
      application in the New South Wales, Australia.
AB  - This paper proposes an integrated modelling approach for location planning of
      radiotherapy treatment services based on cancer incidence and road network-based
      accessibility. Previous research efforts have established travel distance/time
      barriers as a key factor affecting access to cancer treatment services, as well
      as epidemiological studies have shown that cancer incidence rates vary with
      population demography. Our study is built on the evidence that the travel
      distances to treatment centres and demographic profiles of the accessible regions
      greatly influence the uptake of cancer radiotherapy (RT) services. An integrated
      service planning approach that combines spatially-explicit cancer incidence
      projections, and the placement of new RT services based on road network based
      accessibility measures have never been attempted. This research presents a novel
      approach for the location planning of RT services, and demonstrates its viability
      by modelling cancer incidence rates for different age-sex groups in New South
      Wales, Australia based on observed cancer incidence trends; and estimations of
      the road network-based access to current NSW treatment centres. Using three
      indices (General Efficiency, Service Availability and Equity), we show how the
      best location for a new RT centre may be chosen when there are multiple competing
      locations. 

PMID- 26310503
TI  - Severe Jaccoud's arthropathy in systemic lupus erythematosus.
AB  - Jaccoud's arthropathy (JA) is a clinical situation nowadays present mostly in
      systemic lupus erythematosus (SLE). It is characterized by the presence of joint
      deformities such as "swan neck," ulnar deviation and "Z-thumb" resembling
      rheumatoid arthritis (RA) but that are passively correctable and without bone
      erosion on plain radiographs. From our cohort of SLE patients with JA, we
      selected a subgroup with a more severe form of this arthropathy and looked at
      their clinical and laboratory profile as well as studied the magnetic resonance
      imaging (MRI) findings or ultrasound (US) obtained from the hand with most
      evident deformities. Seven SLE patients with a severe form of JA were identified.
      All seven patients have "swan neck," ulnar deviation and "Z-thumb" deformities.
      Two out of seven had "mutilans-type JA" and four had fixed deformities in the
      metacarpophalangeal (MCP) joints. The MRI of the hand with more evident deformity
      clinically performed in six cases and US performed in one case showed mild
      synovitis in five and moderate synovitis in two patients, mild flexor
      tenosynovitis in six and severe tenosynovitis in one. Only two small bone
      erosions were observed in the second and third MCP joints of one patient with
      moderate synovitis. Severe JA compromises the functional capacity of the joints
      and imposes the risk of misdiagnosis of RA. With the improvement of the survival
      rate of SLE and the lack of specific prophylactic or therapeutical measures for
      JA, it is reasonable to assume that more and more cases of severe JA are going to
      be identified. 

PMID- 26310504
TI  - Design of Phenylalanine-Containing Elastin-Derived Peptides Exhibiting Highly
      Potent Self-Assembling Capability.
AB  - In this study, we developed a series of Phe-containing elastin-derived peptide
      analogs, (Phe-Pro-Gly-Val-Gly)n (n = 1-5) and analyzed their reversible
      coacervation properties. Compared to the native elastin-derived repeating peptide
      sequence ((Val-Pro-Gly-Val-Gly)10), one of the Phecontaining 5-mer repeating
      peptide sequences ((Phe-Pro-Gly-Val-Gly)5) clearly exhibited stronger
      coacervation properties. The coacervation of (Phe-Pro-Gly-Val-Gly)5 is nearly the
      same as that of polypeptides (Val-Pro-Gly-Val-Gly)n (n > 40). Although large
      molecular weights (>10,000 Da) are generally required for the coacervation of
      elastin-derived peptides, (Phe-Pro-Gly-Val-Gly)5 exhibited reversible
      coacervation properties despite its low molecular weight (MW = 2,305 Da). High
      performance liquid chromatography (HPLC) and circular dichroism (CD) analysis
      revealed that (Phe-Pro-Gly-Val-Gly)5 has high hydrophobicity and an ordered
      structure with a type II beta-turn, which contributes to the strong coacervation
      ability of the peptide. In addition, (Phe-Pro-Gly-Val-Gly)5 exhibited an
      effective particle size distribution (60-70 nm) at body temperature (37 degrees
      C) and a dispersed small particle size similar to that of the monomer peptides at
      low temperatures. These properties, along with its small size and simple design,
      render the peptide suitable for use in biomaterials, including drug-delivery
      carriers.

PMID- 26310505
TI  - Relationship between 28-year food consumption trends and the 10-year global risk
      of death due to cardiovascular diseases in the adult Warsaw population.
AB  - BACKGROUND: Diet plays an important role in the aetiology of cardiovascular (CV)
      disease. SCORE risk charts are popular and simple tools for the assessment of the
      global risk of CV death. AIM: To evaluate food consumption trends in the adult
      Warsaw population in 1984-2012 and to establish their relationship to the 10-year
      global risk of death due to CV diseases. METHODS: Nutrient intake and CV risk
      factors were assessed in independent representative samples of the Warsaw
      population in the Pol-MONICA projects (in 1984, 1988, 1993, and 2001) and the WAW
      KARD project (in 2012). Overall, these surveys included 3404 men and 3446 women
      aged 35-64 years. The global CV risk was calculated using the SCORE risk chart
      for high-risk European regions. On the basis of the collected data, trends of
      dietary intakes and the SCORE risk values in the years 1984-2012 were estimated
      by linear and nonlinear regressions and correlations. RESULTS: Over the period of
      28 years (1984-2012), a significant decrease in the SCORE risk (by 20% in men and
      by 35% in women) was seen, accompanied by significant changes in the dietary
      habits of the Warsaw population. Declining trends (an exponential model) were
      noted for total energy, total fat, cholesterol, and added animal fat intake.
      Intake of saturated fatty acids decreased until 2001 and increased thereafter (a
      second degree polynomial regression model). These changes in the dietary habits
      of the Warsaw population correlated with the SCORE risk values. Significant
      correlations were noted for total energy, total fat, and dietary cholesterol
      intake in both sexes, and animal fat and saturated fatty acid intake in men, with
      the correlation coefficients ranging from 0.85 to 0.98. CONCLUSIONS: A
      significant reduction in the SCORE risk was seen in the Warsaw population in 1984
      2012, which was associated with positive dietary changes. However, an unexpected
      decrease and reversal of the favourable trends in the structure of fat
      consumption occurred in the last decade.

PMID- 26310506
TI  - Gold-conjugated green tea nanoparticles for enhanced anti-tumor activities and
      hepatoprotection--synthesis, characterization and in vitro evaluation.
AB  - Green tea (GT)-based chemoprevention has shown promising results in various
      cancer models. However, the effective dose may not be far from the toxic dose
      because of inefficient systemic delivery and limited bio-availability of GT
      polyphenols. We have used GT polyphenols to successfully reduce gold to
      corresponding gold nanoparticles (NPs) in a single step; a process that fulfils
      all criteria of green nanotechnology as no "man-made" chemical other than gold
      acids are used. GT and (-) - epigallocatechin-3-gallate (EGCG) conjugated gold
      NPs (diameters <50 nm), showed remarkable stability, significantly rapid cellular
      uptake and excellent in vitro anti-oxidant activities. These NPs were observed to
      be selectively toxic towards cancer cells (Ehrlich's Ascites Carcinoma and MCF-7)
      while showing absolutely no lethality towards normal primary mouse hepatocytes.
      In cancer cells, NPs altered the redox status and limited Nrf2 activation by
      almost 50%. These NPs significantly decreased nuclear translocation of NF-kappaB,
      coupled with decreased phosphorylation of IKB and down-regulation of NF-kappaB
      dependent anti-apoptotic proteins Bcl2 and Akt in a dose-dependent manner,
      triggering onset of apoptosis. Culturing normal hepatocytes with tumor
      conditioned media prompted apoptosis by increasing reactive oxygen species (ROS)
      and depleting the anti-oxidant defense mechanism of hepatocytes. Pre-treatment
      with NPs protected hepatocytes from tumor-induced cellular damage by scavenging
      excess ROS, increasing the levels of reduced glutathione and anti-oxidant
      enzymes. There was evidence of decreased Bax/Bcl2 ratio and active Caspase 3
      levels in these hepatocytes, indicating apoptosis escape. Nanoformulations of GT
      based polyphenols might serve as an operative platform for effective delivery,
      increased bio-availability, enhanced effects and minimal chemotherapy-associated
      toxicities. 

PMID- 26310507
TI  - Homozygous Desmocollin-2 Mutations and Arrhythmogenic Cardiomyopathy.
AB  - Dominant mutations in desmocollin-2 (DSC2) gene cause arrhythmogenic
      cardiomyopathy (ACM), a progressive heart muscle disease characterized by
      ventricular tachyarrhythmias, heart failure, and risk of juvenile sudden death.
      Recessive mutations are rare and are associated with a cardiac or cardiocutaneous
      phenotype. Here, we evaluated the impact of a homozygous founder DSC2 mutation on
      clinical expression of ACM. An exon-by-exon analysis of the DSC2 coding region
      was performed in 94 ACM index patients. The c.536A>G (p.D179G) mutation was
      identified in 5 patients (5.3%), 4 of which resulted to be homozygous carriers.
      The 5 subjects shared a conserved haplotype, strongly indicating a common
      founder. Genetic and clinical investigation of probands' families revealed that
      p.D179G homozygous carriers displayed severe forms of biventricular
      cardiomyopathy without hair or skin abnormalities. The only heterozygous proband,
      who carried an additional variant of unknown significance in alphaT-catenin gene,
      showed a mild form of ACM without left ventricular involvement. All heterozygous
      family members were clinically asymptomatic. In conclusion, this is the first
      homozygous founder mutation in DSC2 gene identified among Italian ACM probands.
      Our findings provide further evidence of the occurrence of recessive DSC2
      mutations in patients with ACM predominantly presenting with biventricular forms
      of the disease. 

PMID- 26310509
TI  - Alterations in the serum biomarkers belonging to different metabolic systems of
      fish (Oreochromis niloticus) after Cd and Pb exposures.
AB  - The serum of vertebrates including human gives sufficient data about the current
      health status of organism in concern. Biomarkers have gained importance in
      evaluation of data from biological monitoring studies. In this study, freshwater
      fish Oreochromis niloticus were individually exposed Cd or Pb using acute (10MUM,
      2 d) and chronic (20MUM, 20 d) exposure protocols to investigate the alterations
      in serum parameters (ALP, ALT, AST, LDH, lipase, glucose, protein, cholesterol
      and triglyceride) and response of the endocrine system functioning in different
      axis, namely HPI (cortisol), HPT (TSH, T3, T4), gonadal (LH, FSH) and prolactin.
      Data showed that except LH, the levels of all hormones decreased significantly
      following exposure to Cd and Pb both in acute and chronic exposures. In acute
      exposures, the activity of ALP and levels of cholesterol and triglyceride
      decreased significantly following both Cd and Pb exposures, while glucose levels
      increased only after Cd exposure. In chronic exposures, both metal exposures
      caused significant decreases in ALP activity and levels of cholesterol and
      triglyceride, though there were increases in glucose level after Cd exposure and
      AST, ALT and LDH levels after Pb exposure. Data emphasized the importance of
      biomarker selection and multiparameter usage of relevant systems in
      ecotoxicological research to achieve proper evaluation of environmental data. 

PMID- 26310508
TI  - Effects of 2,2',4,4'-tetrabromodiphenyl ether (BDE47) on the enzymes of phase I
      (CYP2B1/2) and phase II (SULT1A and COMT) metabolism, and differences in the
      action of parent BDE-47 and its hydroxylated metabolites, 5-OH-BDE-47 and 6-OH
      BDE47, on steroid secretion by luteal cells.
AB  - In this study we determined the effects of BDE-47 on the expression and activity
      of phase I (CYP2B1/2) and phase II (SULT1A and COMT) enzymes, and assessed the
      actions of BDE-47 and its metabolites on luteal steroidogenesis. Luteal cells
      collected during early (ELP), middle (MLP) and late (LLP) luteal phase were
      exposed to BDE-47 (0.5, 25, and 50ng/ml) or metabolites (2.5, 5 and 25ng/ml). BDE
      47 decreased CYP2B1/2 activity and expression but had no effect on SULT1A or
      COMT. BDE-47 exerted a stimulatory action on estrogen secretion in MLP and an
      inhibitory in LLP, but had no effect on progesterone secretion. 5-OH-BDE-47 and 6
      OH-BDE-47 decreased progesterone, but had no effect on estrogen secretion.
      CONCLUSIONS: The inhibitory effect of BDE-47 on CYP2B1/2 suggests the possibility
      of BDE-47 accumulation in the corpus luteum; by affecting steroid secretion and
      steroidogenesis enzymes, BDE-47 and its metabolites can be responsible for
      shortening luteal phase.

PMID- 26310510
TI  - Reframing the concept of alternative livelihoods.
AB  - Alternative livelihood project (ALP) is a widely used term for interventions that
      aim to reduce the prevalence of activities deemed to be environmentally damaging
      by substituting them with lower impact livelihood activities that provide at
      least equivalent benefits. ALPs are widely implemented in conservation, but in
      2012, an International Union for Conservation of Nature resolution called for a
      critical review of such projects based on concern that their effectiveness was
      unproven. We focused on the conceptual design of ALPs by considering their
      underlying assumptions. We placed ALPs within a broad category of livelihood
      focused interventions to better understand their role in conservation and their
      intended impacts. We dissected 3 flawed assumptions about ALPs based on the
      notions of substitution, the homogenous community, and impact scalability.
      Interventions based on flawed assumptions about people's needs, aspirations, and
      the factors that influence livelihood choice are unlikely to achieve conservation
      objectives. We therefore recommend use of a sustainable livelihoods approach to
      understand the role and function of environmentally damaging behaviors within
      livelihood strategies; differentiate between households in a community that have
      the greatest environmental impact and those most vulnerable to resource access
      restrictions to improve intervention targeting; and learn more about the social
      ecological system within which household livelihood strategies are embedded.
      Rather than using livelihood-focused interventions as a direct behavior-change
      tool, it may be more appropriate to focus on either enhancing the existing
      livelihood strategies of those most vulnerable to conservation-imposed resource
      access restrictions or on use of livelihood-focused interventions that establish
      a clear link to conservation as a means of building good community relations.
      However, we recommend that the term ALP be replaced by the broader term
      livelihood-focused intervention. This avoids the implicit assumption that
      alternatives can fully substitute for natural resource-based livelihood
      activities. 

PMID- 26310511
TI  - Resistance status of ticks (Acari; Ixodidae) to amitraz and cypermethrin
      acaricides in Isoka District, Zambia.
AB  - This study was designed to obtain data on the farmer's approach to tick control
      and to determine whether Rhipicephalus appendiculatus Neuman, Amblyomma
      variegatum (Fabricius), and Rhipicephalus (Boophilus) microplus (Canestrini) were
      resistant to amitraz and cypermethrin acaricides, in Isoka District, Zambia.
      Prevailing tick control practices were documented by administering a semi
      structured questionnaire to 80 randomly selected smallholder livestock farmers
      from four agricultural camps (Longwe, Kantenshya, Kapililonga, and Ndeke) in
      Isoka District. Modified larval packet test (LPT) bioassay experiments were used
      to determine the resistance status of the common tick species against amitraz and
      cypermethrin acaricides. Fifty percent of respondents practiced chemical tick
      control with amitraz (27 %) and cypermethrin (23 %) being the acaricides in use,
      and were applied with knapsack sprayers. Less than 3 l of spray wash per animal
      was used which was considerably lower than the recommended delivery rate of 10 l
      of spray wash per animal. No significant susceptibility change to amitraz at 95 %
      confidence level was observed in R. appendiculatus and A. variegatum against
      amitraz. However, a significant change in the susceptibility of R. (Bo.)
      microplus tested with amitraz was detected at 95 % confidence. The test
      population had a lower susceptibility (LD50 0.014 %; LD90 0.023 %) than the
      reference population (LD50 0.013 %; LD90 0.020 %). The results indicated that
      resistance to amitraz was developing in R. (Bo.) microplus. For cypermethrin, no
      significant susceptibility change at 95 % confidence was observed in any of the
      three species and thus resistance to this chemical was not observed. 

PMID- 26310512
TI  - Brain angioarchitecture and intussusceptive microvascular growth in a murine
      model of Krabbe disease.
AB  - Defects of the angiogenic process occur in the brain of twitcher mouse, an
      authentic model of human Krabbe disease caused by genetic deficiency of lysosomal
      beta-galactosylceramidase (GALC), leading to lethal neurological dysfunctions and
      accumulation of neurotoxic psychosine in the central nervous system. Here,
      quantitative computational analysis was used to explore the alterations of brain
      angioarchitecture in twitcher mice. To this aim, customized ImageJ routines were
      used to assess calibers, amounts, lengths and spatial dispersion of CD31(+)
      vessels in 3D volumes from the postnatal frontal cortex of twitcher animals. The
      results showed a decrease in CD31 immunoreactivity in twitcher brain with a
      marked reduction in total vessel lengths coupled with increased vessel
      fragmentation. No significant changes were instead observed for the spatial
      dispersion of brain vessels throughout volumes or in vascular calibers. Notably,
      no CD31(+) vessel changes were detected in twitcher kidneys in which psychosine
      accumulates at very low levels, thus confirming the specificity of the effect.
      Microvascular corrosion casting followed by scanning electron microscopy
      morphometry confirmed the presence of significant alterations of the functional
      angioarchitecture of the brain cortex of twitcher mice with reduction in
      microvascular density, vascular branch remodeling and intussusceptive
      angiogenesis. Intussusceptive microvascular growth, confirmed by histological
      analysis, was paralleled by alterations of the expression of intussusception
      related genes in twitcher brain. Our data support the hypothesis that a marked
      decrease in vascular development concurs to the onset of neuropathological
      lesions in twitcher brain and suggest that neuroinflammation-driven
      intussusceptive responses may represent an attempt to compensate impaired
      sprouting angiogenesis. 

PMID- 26310513
TI  - The efficacy of erythropoietin mouthwash in prevention of oral mucositis in
      patients undergoing autologous hematopoietic SCT: a double-blind, randomized,
      placebo-controlled trial.
AB  - Oral mucositis (OM) as a complication of high-dose chemotherapy is frequently
      occurred in hematopoietic stem cell transplantation (HSCT) settings.
      Erythropoietin (EPO) has anti-inflammatory, antioxidant and wound-healing
      properties and therefore could have an important role in the prevention of OM. We
      conducted a double-blind, randomized, placebo-controlled trial to evaluate the
      EPO mouthwash effect on OM incidence and severity in 80 patients with non
      Hodgkin's lymphoma, Hodgkin disease (HD) or multiple myeloma, undergoing
      autologous hematopoietic stem cell transplantation. Patients received either EPO
      mouthwash (50 IU/ml, 15 ml four times a day) (n = 40) or placebo (n = 40) from
      the starting day of high-dose chemotherapy until day +14 after transplantation or
      until the day of discharge from the hospital, whichever occurred first. OM was
      evaluated daily for 21 days after transplantation or until resolution of OM
      according to World Health Organization oral toxicity scale. The incidence of OM
      (grades 1-4) in the EPO mouthwash group and control group was significantly
      different (27.5% vs 77.5%, p < 0.001). The mean +/- SD of two other parameters of
      OM including maximum intensity OM score (0.60 +/- 1.06 vs 1.67 +/- 1.27) and
      average intensity OM score (0.47 +/- 0.80 vs 1.28 +/- 0.86) was significantly
      lower in the intervention group (p < 0.001). Moreover, the mean +/- SD duration
      of OM was also significantly shorter among the EPO mouthwash recipients (1.92 +/-
      3.42 days vs 5.42 +/- 3.86 days, P < 0.001). Also, the duration of neutropenic
      fever was significantly shorter in the intervention group (2.12 +/- 2.42 days vs
      3.95 +/- 4.01 days, p = 0.016). It is concluded that EPO mouthwash can reduce the
      incidence and duration of OM. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 26310514
TI  - Robot-assisted radical cystectomy.
AB  - Robot-assisted radical cystectomy (RARC) has rapidly penetrated the field of
      urology since its inception in 2003. Several observational studies, retrospective
      reports, and three randomized controlled trials (RCT) have preliminarily
      demonstrated the safety and efficacy of (RARC). Additionally, results from the
      RAZOR RCT will be available in 2016-2017 to better substantiate the use of
      (RARC).

PMID- 26310515
TI  - Stop codon recognition in the early-diverged protozoans Giardia lamblia and
      Trichomonas vaginalis.
AB  - Two classes of polypeptide release factors (RFs) are responsible for maintaining
      accuracy in translation termination; however, their detailed mechanism of action
      and evolutionary history of these factors remain elusive. The structure and
      function of RFs vary in bacteria and eukaryotes, a fact that is suggestive of
      evolutionary changes in the translation termination system. Giardia lamblia
      (Diplomonada) and Trichomonas vaginalis (Parabasalia) are considered as early
      diverged eukaryotes. The class II release factor, eRF3, of Giardia (Gl-eRF3)
      appears to have only one domain that corresponds to EF-1alpha and lacks the N
      terminal domain, similar to that of eRF3 of other organisms. In the present
      study, we show that the chimeric molecules Gl/Sc eRF1 and Tv/Sc eRF1, which are
      composed of the N-terminal domain of Gl-eRF1 or Tv-eRF1, fused to the core domain
      (M and C domain) of Saccharomyces cerevisiae eRF1 (Sc-eRF1), resulting in loss of
      the RF properties of the N-terminal domain. This suggests that the conformation
      of eRF1 for stop codon recognition in Giardia and Trichomonas varies from the
      eRF1s of other eukaryotes, including ciliates and yeast. Further studies using
      intra-N-terminal chimeras of eRF1 indicated that the combination of the GTS loop
      and NIKS motif from Gl-eRF1 and the Y-C-F motif from Sc-eRF1within the N terminal
      domain of hybrid eRF1 could restore UGA, but not UAG and UGA recognition. In
      contrast, the combination of the GTS loop and the NIKS motif of Sc-eRF1 and the Y
      C-F motif of Gl-eRF1 could restore UAG and UAA recognition, but not UGA
      recognition. Thus, these results confirm the findings of previous studies that
      three motifs in eRF1 are necessary for discrimination of the three bases of stop
      codons. The NIKS motif is responsible for recognition of the first two bases of
      UAA and UAG, and the Y-C-F motif identifies the second base of UGA by Gl-eRF1.
      Amino acid residue substitutions in Gl/Sc-eRF1 by corresponding residues of Sc
      eRF1 could change and even restore RF activity, further suggesting different
      conformation of eRF1 are used for stop codon recognition in Giardia and in
      Saccharomyces. 

PMID- 26310516
TI  - Environmental carcinogenesis - 100th anniversary of creating cancer.
AB  - Asbestos is an environmental carcinogen, and asbestos-related diseases represent
      a global-scale environmental issue. Mesothelioma is an aggressive, malignant
      tumor that initially progresses along the surfaces of the pleura and peritoneum
      that is chiefly attributed to asbestos exposure. X-rays are commonly used for
      tumor screening in populations at risk for developing this cancer. We previously
      reported that the N-terminal of mesothelin may be a useful blood marker for early
      diagnosis method for mesothelioma and since then developed an N-terminal of
      mesothelin ELISA kit in collaboration with IBL Co., Ltd. and confirmed its
      utility as a diagnostic system for mesothelioma. Recently, we performed a large
      scale research screening for mesothelioma and showed that it is a good model for
      early diagnosis in at-risk populations. The year 2015 is the 100th anniversary of
      Yamagiwa's great work on coaltar-induced carcinogenesis by formative stimulation
      in 1915 and the 10th year since 2005, "Kubota shock", people recognized that
      asbestos induces mesothelioma. We dedicate this review to this memorial year for
      environmental carcinogenesis. 

PMID- 26310517
TI  - Cerebrovascular correlates of vitamin D deficiency in older adults living near
      the Equator: results from the Atahualpa Project.
AB  - All studies attempting to find an association between vitamin D deficiency and
      cerebrovascular diseases have been conducted at latitudes far away from the
      Equator, where living conditions, cardiovascular risk factors, and sunshine
      exposure are different from tropical regions. We aimed to assess cerebrovascular
      correlates of vitamin D deficiency in community-dwelling older adults living in
      Atahualpa, a village located in rural coastal Ecuador. Out of 267 individuals
      enrolled in the neuroimaging substudy of the Atahualpa Project, 220 (82%) signed
      the informed consent. Mean age of participants was 70.9 +/- 7.8 years, and 126
      (57%) were women. Fifty-four (25%) persons have vitamin D levels <20 ng/ml, 47
      (21%) had ischemic strokes, and 53 (24%) had moderate-to-severe white matter
      hyperintensities of presumed vascular origin. Exposure effect models constructed
      with vitamin D deficiency as the exposure, white matter hyperintensities and
      ischemic stroke as the outcomes, and confounders--age, gender, body mass index,
      physical activity, blood pressure, fasting glucose, total cholesterol, ionized
      calcium, phosphorus, intact parathormone, and serum creatinine--as independent
      variables revealed a significant association of vitamin D deficiency with white
      matter hyperintensities (P = 0.006) but not with ischemic strokes (P = 0.359).
      This study shows an association of vitamin D deficiency with diffuse subcortical
      brain damage in older adults living in a tropical region. Lack of awareness of
      the importance of vitamin D deficiency might be one of the factors influencing
      the high prevalence of white matter hyperintensities of presumed vascular origin
      in underserved Latin American populations.

PMID- 26310518
TI  - A Designed TiO2 /Carbon Nanocomposite as a High-Efficiency Lithium-Ion Battery
      Anode and Photocatalyst.
AB  - Herein, a peapod-like TiO2 /carbon nanocomposite has successfully been
      synthesized by a rational method for the first time. The novel nanostructure
      exhibits a distinct feature of TiO2 nanoparticles encapsulated inside and the
      carbon fiber coating outside. In the synthetic process, H2 Ti3 O7 nanotubes serve
      as precursors and templates, and glucose molecules act as the green carbon
      source. With the alliciency of hydrogen bonding between H2 Ti3 O7 and glucose, a
      thin polymer layer is hydrothermally assembled and subsequently converted into
      carbon fibers through calcinations under an inert atmosphere. Meanwhile, the
      precursors of H2 Ti3 O7 nanotubes are transformed into the TiO2 nanoparticles
      encapsulated in carbon fibers. The achieved unique nanocomposites can be used as
      excellent anode materials in lithium-ion batteries (LIBs) and photocatalytic
      reagents in the degradation of rhodamine B. Due to the synergistic effect derived
      from TiO2 nanoparticles and carbon fibers, the obtained peapod-like TiO2 /carbon
      cannot only deliver a high specific capacity of 160 mAh g(-1) over 500 cycles in
      LIBs, but also perform a much faster photodegradation rate than bare TiO2 and
      P25. Furthermore, owing to the low cost, environmental friendliness as well as
      abundant source, this novel TiO2 /carbon nanocomposite will have a great
      potential to be extended to other application fields, such as specific catalysis,
      gas sensing, and photovoltaics.

PMID- 26310519
TI  - A Rhizobium radiobacter Histidine Kinase Can Employ Both Boolean AND and OR Logic
      Gates to Initiate Pathogenesis.
AB  - The molecular logic gates that regulate gene circuits are necessarily intricate
      and highly regulated, particularly in the critical commitments necessary for
      pathogenesis. We now report simple AND and OR logic gates to be accessible within
      a single protein receptor. Pathogenesis by the bacterium Rhizobium radiobacter is
      mediated by a single histidine kinase, VirA, which processes multiple small
      molecule host signals (phenol and sugar). Mutagenesis analyses converged on a
      single signal integration node, and finer functional analyses revealed that a
      single residue could switch VirA from a functional AND logic gate to an OR gate
      where each of two signals activate independently. Host range preferences among
      natural strains of R. radiobacter correlate with these gate logic strategies.
      Although the precise mechanism for the signal integration node requires further
      analyses, long-range signal transmission through this histidine kinase can now be
      exploited for synthetic signaling circuits.

PMID- 26310521
TI  - Peer and near-peer OSCE examiners.

PMID- 26310520
TI  - Impact of centralized diagnostic review on quality of initial staging in Hodgkin
      lymphoma: experience of the German Hodgkin Study Group.
AB  - Accurate clinical staging is crucial for adequate risk-adapted treatment in
      Hodgkin lymphoma (HL) to prevent patients from under- or over-treatment. Within
      the latest German Hodgkin Study Group trial generation, diagnostic findings such
      as histopathology, computerized tomography imaging and clinical risk factors were
      re-evaluated by expert panels. Here, we retrospectively analysed 5965 patients
      and identified 399 in who major discordant findings changed their first-line
      treatment allocation. Histopathology review did not confirm the initial diagnosis
      of HL in 87 patients. Treatment allocation was revised in 312 of the remaining
      5878 patients: 176 were assigned to a higher and 128 to a lower risk group,
      respectively; the correct treatment group remained unclear in 8 patients. Cases
      of revised treatment allocation accounted for 9.8%, 6.0%, 0.8%, and 14.8% of
      patients initially assigned to the HD13, HD14, HD15 trials and stage IA
      lymphocyte-predominant HL project, respectively. Most revisions were due to wrong
      application of clinical stage (20.5% of 312 patients with revised treatment
      group), histological subtype (9.0%) or the risk factors >=3 involved areas
      (46.8%) or large mediastinal mass (9.3%). In conclusion, centralized review by
      experienced experts changed risk-adapted first-line treatment in a relevant
      proportion of HL patients. Quality control measures clearly improve the accuracy
      of treatment and should be implemented in clinical practice. 

PMID- 26310522
TI  - Origins of the Indenofluorene Project: Serendipity and Other Surprises.

PMID- 26310523
TI  - Geological connectivity drives microbial community structure and connectivity in
      polar, terrestrial ecosystems.
AB  - Landscape heterogeneity impacts community assembly in animals and plants, but it
      is not clear if this ecological concept extends to microbes. To examine this
      question, we chose to investigate polar soil environments from the Antarctic and
      Arctic, where microbes often form the major component of biomass. We examined
      soil environments that ranged in connectivity from relatively well-connected
      slopes to patchy, fragmented landforms that comprised isolated frost boils. We
      found landscape connectedness to have a significant correlation with microbial
      community structure and connectivity, as measured by co-occurrence networks.
      Soils from within fragmented landforms appeared to exhibit less local
      environmental heterogeneity, harboured more similar communities, but fewer
      biological associations than connected landforms. This effect was observed at
      both poles, despite the geographical distances and ecological differences between
      them. We suggest that microbial communities inhabiting well-connected landscape
      elements respond consistently to regional-scale gradients in biotic and edaphic
      factors. Conversely, the repeated freeze thaw cycles that characterize fragmented
      landscapes create barriers within the landscape and act to homogenize the soil
      environment within individual frost boils and consequently the microbial
      communities. We propose that lower microbial connectivity in the fragmented
      landforms is a function of smaller patch size and continual disturbances
      following soil mixing.

PMID- 26310524
TI  - Non Steroidal Anti Inflammatory Drugs As Gatekeepers Of Colon Carcinoma Highlight
      New Scenarios Beyond Cyclooxygenases Inhibition.
AB  - Epidemiological data suggest that Non Steroidal Anti Inflammatory Drugs (NSAIDs)
      and Cyclooxygenase 2 (COX2) inhibitors (COXibs) can exert chemopreventive and
      antitumour effects in many human neoplasia. This is particularly true in colon
      cancer (CC), where the regular assumption of these molecules has been shown to
      exert chemopreventive and chemotherapeutic effects. Since the late '90s, there
      has been a progressive increase in experimental evidence, indicating that in CC
      the antiproliferative effects of NSAIDs and COXibs could be both dependent on and
      independent of COXs inhibition, and that these effects do not necessarily exclude
      each other. This review will examine some of these COX-independent cellular
      pathways, with a focus on those involved in the inhibition of CC cells
      proliferation through transcription factors crosstalk. 

PMID- 26310525
TI  - Exploring the concept of need in people with very severe chronic obstructive
      pulmonary disease: a qualitative study.
AB  - BACKGROUND: Despite apparent unmet needs, people with chronic obstructive
      pulmonary disease (COPD) rarely ask for help. We explored the concept of need
      from the perspective of patients, their family carers and professionals. METHODS:
      We recruited inpatients at two National Health Service (NHS) Lothian hospitals to
      a structured, holistic review of care needs delivered at home by a respiratory
      nurse 4 weeks postdischarge. Using semistructured interviews and group
      discussions, review notes and field-notes we explored the views of patients,
      carers and professionals on perceptions of need and the actions requested. Data
      were analysed thematically using Bradshaw's classification of need. RESULTS: 14
      patients, 3 carers, 28 professionals provided 36 interviews and 2 discussion
      groups. Few needs were identified by our intervention and few actions planned.
      Professionals identified 'normative' needs some of which had been addressed
      during routine discharge planning. Other needs (physical/psychological
      limitations, social/financial concerns, existential issues) were 'felt' by
      patients and carers but articulated in response to the researcher's questions
      rather than actively 'expressed'. Patients often did not wish any action to
      address the problems, preferring care from family members rather than formal
      agencies. Many spoke of the over-arching importance of retaining a sense of
      independence and autonomy, considering themselves as ageing rather than ill.
      CONCLUSIONS: In contrast to professionally-defined 'normative' needs, patients
      rarely perceived themselves as needy, accepting their 'felt' needs as the result
      of a disability to which they had now adapted. Sensitive approaches that foster
      independence may enable patients to 'express' needs that are amenable to help
      without disturbing the adaptive equilibrium they have achieved. TRIAL
      REGISTRATION NUMBER: NCT01650480.

PMID- 26310526
TI  - Bifunctional enhancement of oxygen reduction reaction activity on Ag catalysts
      due to water activation on LaMnO3 supports in alkaline media.
AB  - Ag is considered to be one of the best candidates for oxygen reduction reaction
      electrocatalysts in alkaline media for application in various electrochemical
      energy devices. In this study, we demonstrate that water activation is a key
      factor in enhancing the ORR activity in alkaline media, unlike in acid
      environments. Ag supported on LaMnO3 having a high oxophilicity showed a markedly
      higher ORR activity than that on carbon with inert surfaces. Through various
      electrochemical tests, it was revealed that the origin of the enhanced ORR
      activity of Ag/LaMnO3 is the bifunctional effect mainly due to the water
      activation at the interface between Ag and LaMnO3. Furthermore, the ligand effect
      due to the charge transfer from Mn to Ag leads to the enhancement of both oxygen
      activation on Ag and water activation on Mn sites, and hence, an improvement in
      the ORR activity of Ag/LaMnO3. On the other hand, the strain effect based on the
      fine structure variation in the lattice was negligible. We therefore suggest that
      the employment of a co-catalyst or support with highly oxophilic nature and the
      maximization of the interface between catalyst and support should be considered
      in the design of electrocatalysts for the ORR in alkaline media. 

PMID- 26310527
TI  - Assessment of patient-reported outcome measures in the surgical treatment of
      patients with gastric cancer.
AB  - BACKGROUND: Gastric cancer is responsible for 10 % of all cancer-related deaths
      worldwide. With improved operative techniques and neo-adjuvant therapy, survival
      rates are increasing. Outcomes of interest are shifting to quality of life (QOL),
      with many different tools available. The aim of this study was to assess which
      patient-reported outcome measures (PROMs) are used to measure QOL after a
      gastrectomy for cancer. METHODS: A comprehensive search was conducted for
      original articles investigating QOL after gastrectomy. Two authors independently
      selected relevant articles, conducted clinical appraisal and extracted data (P.J.
      and J.S.). RESULTS: Out of 3414 articles, 26 studies were included, including a
      total of 4690 patients. These studies included ten different PROMs, which could
      be divided into generic, symptom-specific and disease-specific questionnaires.
      The EORTC and the FACT questionnaires use an oncological overall QOL module and
      an organ-specific module. Only one validation study regarding the use of the
      EORTC after surgery for gastric cancer was available, demonstrating good
      psychometric properties and clinical validity. CONCLUSIONS: A great variety of
      PROMs are being used in the measurement of QOL after surgery for gastric cancer.
      A questionnaire with a general module along with a disease-specific module for
      the assessment of QOL seems most desirable, such as the EORTC and the FACT with
      their specific modules. Both are developed in different treatment modalities,
      such as in surgical patients. EORTC is the most widely used questionnaire and
      therefore allows for comparison of new studies to existing data. Future studies
      are needed to assess content validity in surgical gastric cancer patients.

PMID- 26310528
TI  - The six-minute walk test as a measure of postoperative recovery after colorectal
      resection: further examination of its measurement properties.
AB  - INTRODUCTION: Patients, clinicians and researchers seek an easy, reproducible and
      valid measure of postoperative recovery. The six-minute walk test (6MWT) is a low
      cost measure of physical function, which is a relevant dimension of recovery. The
      aim of the present study was to contribute further evidence for the validity of
      the 6MWT as a measure of postoperative recovery after colorectal surgery.
      METHODS: This study involved a sample of 174 patients enrolled in three previous
      randomized controlled trials. Construct validity was assessed by testing the
      hypotheses that the distance walked in 6 min (6MWD) at 4 weeks after surgery is
      greater (1) in younger versus older patients, (2) in patients with higher
      preoperative physical status versus lower, (3) after laparoscopic versus open
      surgery, (4) in patients without postoperative complications versus with
      postoperative complications; and that 6MWD (5) correlates cross-sectionally with
      self-reported physical activity as measured with a questionnaire (CHAMPS).
      Statistical analysis was performed using linear regression and Spearman's
      correlation. The COnsensus-based Standards for the selection of health
      Measurement INstruments (COSMIN) checklist was used to guide the formulation of
      hypotheses and reporting of results. RESULTS: One hundred and fifty-one patients
      who completed the 6MWT at 4 weeks after surgery were included in the analysis.
      All hypotheses tested for construct validity were supported by the data. Older
      age, poorer physical status, open surgery and occurrence of postoperative
      complications were associated with clinically relevant reduction in 6MWD (>19 m).
      There was a moderate positive correlation between 6MWD and patient-reported
      physical activity (r = 0.46). CONCLUSIONS: This study contributes further
      evidence for the construct validity of the 6MWT as a measure of postoperative
      recovery after colorectal surgery. Results from this study support the use of the
      6MWT as an outcome measure in studies evaluating interventions aimed to improve
      postoperative recovery.

PMID- 26310529
TI  - Diagnostic efficacy of endoscopic ultrasound-guided needle sampling for upper
      gastrointestinal subepithelial lesions: a meta-analysis.
AB  - BACKGROUND: An increasing number of studies have been conducted on the use of
      endoscopic ultrasound (EUS)-guided needle sampling for upper gastrointestinal
      subepithelial lesions (SEL). However, reported diagnostic efficacy varies
      greatly. OBJECTIVE: To summarize up current evidences on the diagnostic efficacy
      of EUS-guided needle sampling for upper GI SEL. METHOD: A reproducible strategy
      was used to search four databases. Search results were evaluated for eligibility,
      and the quality of eligible studies was assessed by QUADAS-2. Pooled efficacy of
      EUS-guided needle sampling in upper GI SEL was calculated. Procedure-related
      complications, diagnostic errors, and independent factors related to a higher
      success rate were also recorded and analyzed. RESULTS: Seventeen studies,
      comprising 978 attempts of EUS-guided needle sampling, were included in a meta
      analysis. Pooled diagnostic rate of EUS-guided needle sampling was 59.9 %, with a
      heterogeneity I (2) of 55.2 %. Subgroup analysis showed no difference in
      diagnostic rate among fine needle aspiration (FNA), trucut needle biopsy (TCB),
      and fine needle biopsy (FNB), or among 19-, 22-, and 25-G needles. Subgroup
      analysis and meta-regression suggested that the cell block method might be
      correlated with a higher diagnostic rate. Few severe complications were reported.
      Diagnosis errors were rare. CONCLUSION: EUS-guided needle sampling is a safe, but
      only moderately effective method for pathology diagnosis of upper GI SEL. Choice
      of FNA/TCB/FNB, or 19 G/22 G/25 G does not seem to alter the overall diagnostic
      rate.

PMID- 26310530
TI  - Laparoscopic splenic hilar lymph node dissection for proximal gastric cancer
      using integrated three-dimensional anatomic simulation software.
AB  - BACKGROUND: Laparoscopic lymph node (LN) dissection along the distal splenic
      artery (Station No. 11d) and around the splenic hilum (Station No. 10) remains
      challenging even for skilled surgeons. The major reason for the difficulty is the
      complex, multifarious anatomy of the splenic vessels. The latest integrated three
      dimensional (3D) simulations may facilitate this procedure. METHODS: Usefulness
      of 3D simulation was investigated during 20 laparoscopic total gastrectomies with
      splenic hilar LN dissection while preserving the spleen and pancreas (LTG + PSP)
      or with splenectomy (LTG + S). Clinical information acquired by 3D simulation and
      the consistency of the virtual and real images were evaluated. Furthermore,
      clinical data of these patients were compared with that of the patients who
      underwent the same surgery before the introduction of 3D simulation (n = 10), to
      clarify its efficacy. RESULTS: The vascular architecture and morphologic
      characteristics were clearly demonstrated in 3D simulation, with sufficient
      consistency. The median durations of 14 LTG + PSP and 6 LTG + S operations were
      318 and 322 min, respectively. The estimated blood losses were 18 and 38 g,
      respectively. There were no deaths. One postoperative peritoneal abscess (grade
      II according to Clavien-Dindo) was recorded. A comparison of clinical parameters
      between surgeries without or with 3D simulation showed no differences in
      operation time, blood loss, or complication rate; however, the number of
      retrieved No. 10 LNs has significantly increased in cases with the use of 3D
      simulation (p = 0.006). CONCLUSIONS: This kind of surgery is not easy to perform,
      but the latest 3D computed tomography simulation technology has made it possible
      to reduce the degree of difficulty and also to enhance the quality of surgery,
      potentially leading to widespread use of these techniques.

PMID- 26310531
TI  - Microcomplications in laparoscopic cholecystectomy: impact on duration of surgery
      and costs.
AB  - BACKGROUND: In the era of cost-constrained health care, optimal resource
      utilisation becomes fundamental in daily clinical practice. Currently, processes
      during surgery are poorly defined and workflows need to be scrutinised. This
      investigation aimed at identifying interruptions of surgical workflow and
      quantifying their impact on the duration of surgery and costs. METHODS:
      Interruptions of surgical workflow were defined as microcomplications (MC) and
      divided into the following subgroups: communication-related (CR), instrument
      changes (IC), missing instruments (MI), instrument failure (IF), waiting for a
      senior surgeon (SS), anaesthesia-related (AR) and position changes (PC). Audio
      video records of laparoscopic cholecystectomies were reviewed regarding type,
      frequency and duration of MC. Risk factors for MC were investigated in a
      multivariable linear regression analysis. The costs of MC due to intraoperative
      delay were calculated. RESULTS: Twenty audio-video records of laparoscopic
      cholecystectomies with a total duration of 28.9 h were reviewed. The median
      frequency of MC was 95 events/h with an overall duration of 452 min,
      corresponding to a delay of 15.6 min/h. Most frequent causes for MC were CR (32
      events/h) and IC (54 events/h), leading to a total delay of 6.5 min/h for CR and
      4.5 min/h for IC, respectively. MI and IF were less frequent (2.0 and 5.4
      events/h), but single events lasted longer, resulting in a total delay of 1.4
      min/h in MI and 2.1 min/h in IF. Intraoperative delays due to SS, AR or PC were
      rare. Multivariable regression analysis revealed previous abdominal surgery and
      cholecystitis as risk factors for a longer duration of MC (p = 0.004; p = 0.046).
      Based on OR minute costs of ? 31.98, the delay due to MC led to additional costs
      of ? 499/h. CONCLUSIONS: MC cause relevant intraoperative delay and increased
      costs. Step-by-step protocols for a laparoscopic cholecystectomy may lead to a
      reduction in MC and should be further evaluated.

PMID- 26310532
TI  - Laparoscopic common bile duct exploration using V-Loc suture with insertion of
      endobiliary stent.
AB  - BACKGROUND: The treatment of concomitant gallbladder (GB) and common bile duct
      (CBD) stones is still variable, without a standard treatment protocol. Endoscopic
      retrograde cholangiopancreatography followed by laparoscopic cholecystectomy is
      widely being used, but laparoscopic common bile duct exploration (LCBDE) is also
      being widely performed. We present our method of LCBDE, with anterograde
      insertion of an endobiliary stent and primary closure of the CBD using
      unidirectional barbed suture. METHODS: From November 2013 to March 2015, LCBDE
      was performed on 15 consecutive patients. Chart review was performed to analyze
      demographic data and perioperative data. After dissection of the GB from the
      liver bed, the CBD is dissected and a choledochotomy is made. A choledochoscope
      is inserted in the CBD, and using various methods, CBD stones are extracted. An
      endobiliary stent is inserted, and the CBD is closed using unidirectional barbed
      sutures. RESULTS: Mean age of the patients was 64.7 +/- 12.5 years. Of the 15
      patients, six patients (40 %) were male and nine patients (60 %) were female. The
      average operation time and postoperative stay were 90.7 +/- 32.5 min and 4.3 +/-
      1.2 days, respectively. There were no significant complications such as
      postoperative bleeding, bile leakage, or biliary stricture. CONCLUSIONS: LCBDE
      using barbed V-Loc suture with insertion of endobiliary stent is a safe, feasible
      treatment modality that is easily reproducible. Our preliminary results show a
      zero complication rate, with an acceptable operation time.

PMID- 26310533
TI  - Hemorrhage control for laparoscopic hepatectomy: technical details and predictive
      factors for intraoperative blood loss.
AB  - BACKGROUND: Controlling bleeding during laparoscopic hepatectomy (LH) is
      technically demanding, but reportedly associated with less estimated blood loss
      (EBL) than open surgery. The present study aimed to describe and evaluate
      hemorrhage control techniques during LH and identify predictors of high
      intraoperative EBL. METHODS: The data of 438 consecutive patients undergoing LH
      between 1995 and 2012 were reviewed. Bleeding control was facilitated by the
      proper use of hemostatic devices and surgical maneuvers unique to LH and by
      preserving intra-abdominal pressure. EBL was evaluated among three groups of 146
      patients in each group: 1995-2006 (group A), 2006-2009 (group B), and 2009-2012
      (group C). We also sought factors that predicted EBL >=800 mL. RESULTS: Mean EBL
      decreased overtime from groups A to C: group A, 378 +/- 619 mL; group B, 293 +/-
      391 mL; groups C, 257 +/- 366 mL; P = 0.127. Transfusion rate was 6.7 % in group
      A, 5.5 % in group B, and 4.8 % in group C (P = 0.743). Hypertension (odds ratio
      (OR) 2.82, 95 % confidence interval CI 1.37-5.78; P = 0.006), preoperative
      chemotherapy (OR 2.55, 95 % CI 1.26-5.31; P = 0.009), resection of
      posterosuperior segments (OR 3.73, 95 % CI 1.33-12.17; P = 0.012), and major
      hepatectomy (OR 4.21, 95 % CI 1.64-13.02; P < 0.001) independently predicted high
      EBL. CONCLUSIONS: Improvements in bleeding control techniques over time have
      reduced EBL during LH. The use of these techniques and an understanding of the
      predictive factors for high EBL will help surgeons improve outcomes after LH.

PMID- 26310534
TI  - Transanal total mesorectal excision for rectal cancer: a preliminary report.
AB  - BACKGROUND: Currently, the majority cases of the novel down-to-up transanal total
      mesorectal excision (TaTME) were performed in a hybrid approach with conventional
      laparoscopic assistance because of less operative difficulty. However, although
      cases are limited, the successes of TaTME in a pure approach (without
      laparoscopic assistance) indicate that the costly and less mini-invasive hybrid
      TaTME could be potentially avoided. METHODS: In the present single institutional,
      prospective study, we attempted to demonstrate the safety and feasibility of this
      approach in rectal cancer by evaluating the short-term results of our first 20
      TaTME cases. For the majority of cases, we adopted a strategy that laparoscopic
      assistance was not introduced unless it was required during the planned pure
      TaTME procedure. RESULTS: A total of 20 patients (12 males and 8 females) were
      analyzed in this study, including 11 cases (55 %) of pure TaTME and 9 cases (45
      %) of hybrid TaTME. Overall, the median operative time was 200 min (range 70
      420), along with a median estimated blood loss of 50 ml (range 20-800). Morbidity
      rate was 20 % (one urethral injury, two urinary retentions, one anastomotic
      hemorrhage and one mild anastomotic leak). The median number of harvested lymph
      nodes was 12 (range 1-20). All specimens were intact in mesorectum without
      positive distal and circumferential resection margins. Among the 15 patients who
      were preoperatively scheduled to undertake pure TaTME, four patients (26.7 %)
      required converting to laparoscopic assistance. Moreover, among these 15
      patients, the results of the comparative analysis between female and male
      subgroups favor the former, suggesting easier operation in them. CONCLUSION: This
      preliminary study demonstrates that TaTME in rectal cancer is safe and feasible.
      The strategy of not introducing laparoscopic assistance unless it is required
      while performing the planned pTaTME should be cautiously explored. Further
      studies with larger sample size and longer follow-up are warranted.

PMID- 26310535
TI  - Laparoscopic management of liver metastases from uveal melanoma.
AB  - BACKGROUND: Although uveal melanoma is a rare disease, its metastasis to the
      liver is associated with a poor survival. The aim of this study is to analyze the
      survival after surgical treatment of uveal melanoma metastases to the liver.
      METHODS: Within 15 years, 44 patients with uveal melanoma metastases to the liver
      were managed at a single center. Medical records were reviewed to identify
      patients who underwent surgical treatment of their liver disease. Clinical and
      oncologic results were compared to those patients who were managed otherwise. T
      test, Chi-square test, and Kaplan-Meier survival analyses were performed.
      RESULTS: There were 16 patients who underwent surgical treatment (laparoscopic
      liver resection, n = 2 and laparoscopic radiofrequency ablation, n = 14),
      compared to 28 patients who received systemic therapy. The groups were similar
      regarding demographics and size of primary tumor. The interval between diagnoses
      of primary tumor and liver metastases was longer for the surgical group (58 vs 22
      months, respectively, p = 0.010). Although the dominant liver tumor size was
      similar, the average number of liver tumors was 4 in the surgical group and 10 in
      the systemic therapy group (p < 0.0001). The median survival after diagnosis of
      liver metastases was 35 months in the surgical group and 15 months in the
      systemic therapy group (p <= 0.0001). Five-year survival was zero in the systemic
      therapy group and 22 % in the surgical group. CONCLUSIONS: This study shows that
      surgical treatment of liver metastases in selected patients with uveal melanoma,
      who have limited liver tumor burden and a long interval to metastases
      development, may result in long-term survival.

PMID- 26310537
TI  - Thermal crosstalk in 3-dimensional RRAM crossbar array.
AB  - High density 3-dimensional (3D) crossbar resistive random access memory (RRAM) is
      one of the major focus of the new age technologies. To compete with the ultra
      high density NAND and NOR memories, understanding of reliability mechanisms and
      scaling potential of 3D RRAM crossbar array is needed. Thermal crosstalk is one
      of the most critical effects that should be considered in 3D crossbar array
      application. The Joule heat generated inside the RRAM device will determine the
      switching behavior itself, and for dense memory arrays, the temperature
      surrounding may lead to a consequent resistance degradation of neighboring
      devices. In this work, thermal crosstalk effect and scaling potential under
      thermal effect in 3D RRAM crossbar array are systematically investigated. It is
      revealed that the reset process is dominated by transient thermal effect in 3D
      RRAM array. More importantly, thermal crosstalk phenomena could deteriorate
      device retention performance and even lead to data storage state failure from LRS
      (low resistance state) to HRS (high resistance state) of the disturbed RRAM cell.
      In addition, the resistance state degradation will be more serious with
      continuously scaling down the feature size. Possible methods for alleviating
      thermal crosstalk effect while further advancing the scaling potential are also
      provided and verified by numerical simulation. 

PMID- 26310536
TI  - The stability and change of etiological influences on depression, anxiety
      symptoms and their co-occurrence across adolescence and young adulthood.
AB  - BACKGROUND: Depression and anxiety persist within and across diagnostic
      boundaries. The manner in which common v. disorder-specific genetic and
      environmental influences operate across development to maintain internalizing
      disorders and their co-morbidity is unclear. This paper investigates the
      stability and change of etiological influences on depression, panic, generalized,
      separation and social anxiety symptoms, and their co-occurrence, across
      adolescence and young adulthood. METHOD: A total of 2619 twins/siblings
      prospectively reported symptoms of depression and anxiety at mean ages 15, 17 and
      20 years. RESULTS: Each symptom scale showed a similar pattern of moderate
      continuity across development, largely underpinned by genetic stability. New
      genetic influences contributing to change in the developmental course of the
      symptoms emerged at each time point. All symptom scales correlated moderately
      with one another over time. Genetic influences, both stable and time-specific,
      overlapped considerably between the scales. Non-shared environmental influences
      were largely time- and symptom-specific, but some contributed moderately to the
      stability of depression and anxiety symptom scales. These stable, longitudinal
      environmental influences were highly correlated between the symptoms.
      CONCLUSIONS: The results highlight both stable and dynamic etiology of depression
      and anxiety symptom scales. They provide preliminary evidence that stable as well
      as newly emerging genes contribute to the co-morbidity between depression and
      anxiety across adolescence and young adulthood. Conversely, environmental
      influences are largely time-specific and contribute to change in symptoms over
      time. The results inform molecular genetics research and transdiagnostic
      treatment and prevention approaches.

PMID- 26310538
TI  - Heart rate response to regadenoson: Making the case for its value in clinical
      practice.

PMID- 26310539
TI  - Maternal prepregnancy obesity and cause-specific stillbirth.
AB  - BACKGROUND: In high-income countries, maternal obesity is one of the most
      important modifiable causes of stillbirth, yet the pathways underpinning this
      association remain unclear. OBJECTIVE: We estimated the association between
      maternal prepregnancy body mass index (BMI) and the risk of stillbirth defined by
      pathophysiologic contributors or causes. DESIGN: Using a case-cohort design, we
      randomly sampled 1829 singleton deliveries from a cohort of 68,437 eligible
      deliveries at Magee-Womens Hospital in Pittsburgh, Pennsylvania (2003-2010), and
      augmented it with all remaining cases of stillbirth for a total of 658 cases.
      Stillbirths were classified based on probable cause(s) of death (maternal medical
      conditions, obstetric complications, fetal abnormalities, placental diseases, and
      infection). A panel of clinical experts reviewed medical records, placental
      tissue slides and pathology reports, and fetal postmortem reports of all
      stillbirths. Causes of fetal death were assigned by using the Stillbirth
      Collaborative Research Network Initial Causes of Fetal Death protocol from the
      Eunice Kennedy Shriver National Institute of Child Health and Human Development.
      Proportional hazards models were used to estimate the BMI-stillbirth association
      after adjustment for confounders. RESULTS: The rate of stillbirth among lean,
      overweight, obese, and severely obese women was 7.7, 10.6, 13.9, and 17.3 per
      1000 live-born and stillborn infants, respectively. Adjusted stillbirth HRs (95%
      CIs) were 1.4 (1.1, 1.8) for overweight, 1.8 (1.3, 2.4) for obese, and 2.0 (1.5,
      2.8) for severely obese women, respectively, compared with lean women;
      associations strengthened when limited to antepartum stillbirths. Obesity and
      severe obesity were associated with stillbirth resulting from placental diseases,
      hypertension, fetal anomalies, and umbilical cord abnormalities. BMI was not
      related to stillbirth caused by placental abruption, obstetric conditions, or
      infection. CONCLUSIONS: Multiple mechanisms appear to link obesity to stillbirth.
      Interventions to reduce stillbirth among obese mothers should consider targeting
      stillbirth due to hypertension and placental diseases-the most common causes of
      fetal death in this at-risk group.

PMID- 26310540
TI  - Latent iron deficiency at birth influences auditory neural maturation in late
      preterm and term infants.
AB  - BACKGROUND: In utero latent iron deficiency has been associated with abnormal
      neurodevelopmental outcomes during childhood. Its concomitant effect on auditory
      neural maturation has not been well studied in late preterm and term infants.
      OBJECTIVE: The objective was to determine whether in utero iron status is
      associated with auditory neural maturation in late preterm and term infants.
      DESIGN: This prospective cohort study was performed at Sir Ganga Ram Hospital,
      New Delhi, India. Infants with a gestational age >=34 wk were eligible unless
      they met the exclusion criteria: craniofacial anomalies, chromosomal disorders,
      hemolytic disease, multiple gestation, third-trimester maternal infection,
      chorioamnionitis, toxoplasmosis, other infections, rubella, cytomegalovirus
      infection, and herpes simplex virus infections (TORCH), Apgar score <5 at 5 min,
      sepsis, cord blood not collected, or auditory evaluation unable to be performed.
      Sixty consecutive infants with risk factors for iron deficiency, such as small
      for gestational age and maternal diabetes, and 30 without risk factors for iron
      deficiency were enrolled. Absolute wave latencies and interpeak latencies,
      evaluated by auditory brainstem response within 48 h after birth, were measured
      and compared between infants with latent iron deficiency (serum ferritin <=75
      ng/mL) and infants with normal iron status (serum ferritin >75 ng/mL) at birth.
      RESULTS: Twenty-three infants had latent iron deficiency. Infants with latent
      iron deficiency had significantly prolonged wave V latencies (7.10 +/- 0.68
      compared with 6.60 +/- 0.66), III-V interpeak latencies (2.37 +/- 0.64 compared
      with 2.07 +/- 0.33), and I-V interpeak latencies (5.10 +/- 0.57 compared with
      4.72 +/- 0.56) compared with infants with normal iron status (P < 0.05). This
      difference remained significant on regression analyses after control for
      confounders. No difference was noted between latencies I and III and interpeak
      latencies I-III. CONCLUSION: Latent iron deficiency is associated with abnormal
      auditory neural maturation in infants at >=34 wk gestational age. This trial was
      registered at clinicaltrials.gov as NCT02503397.

PMID- 26310542
TI  - Decreased Na(+) influx lowers hippocampal neuronal excitability in a mouse model
      of neonatal influenza infection.
AB  - Influenza virus infection is one of common infectious diseases occurring
      worldwide. The human influenza virus can infect the central nervous system and
      cause brain dysfunctions affecting cognition and spatial memory. It has been
      previously shown that infection with the influenza viral protein within the
      hippocampus decreases Ca(2+) influx and reduces excitatory postsynaptic currents.
      However, the neuronal properties of animals surviving neonatal infection have not
      been investigated. Using a mouse model of neonatal influenza infection, we
      performed thorough electrophysiological analyses of hippocampal
      neurotransmission. We found that animals surviving the infection exhibited
      reduced spontaneous transmission with no significant defects in evoked
      neurotransmission. Interestingly, the hippocampus of the infected group conducted
      synaptic transmission with less fidelity upon repeated stimulations and failed to
      generate action potentials faithfully upon step current injections primarily due
      to reduced Na(+) influx. The reversal potential for the Na(+) current was
      hyperpolarized and the activation of Na(+) channels was slower in the infected
      group while the inactivation process was minimally disturbed. Taken together, our
      observations suggest that neonatally infected offsprings exhibit noticeable
      deficits at rest and severe failures when higher activity is required. This study
      provides insight into understanding the cellular mechanisms of influenza
      infection-associated functional changes in the brain. 

PMID- 26310541
TI  - Risk of non-hematologic cancer in individuals with high-count monoclonal B-cell
      lymphocytosis.
AB  - It is unknown whether individuals with monoclonal B-cell lymphocytosis (MBL) are
      at risk for adverse outcomes associated with chronic lymphocytic leukemia (CLL),
      such as the risk of non-hematologic cancer. We identified all locally residing
      individuals diagnosed with high-count MBL at Mayo Clinic between 1999 and 2009
      and compared their rates of non-hematologic cancer with that of patients with CLL
      and two control cohorts: general medicine patients and patients who underwent
      clinical evaluation with flow cytometry but who had no hematologic malignancy.
      After excluding individuals with prior cancers, there were 107 high-count MBL
      cases, 132 CLL cases, 589 clinic controls and 482 flow cytometry controls. With
      4.6 years median follow-up, 14 (13%) individuals with high-count MBL, 21 (4%)
      clinic controls (comparison MBL P<0.0001), 18 (4%) flow controls (comparison MBL
      P=0.0001) and 16 (12%) CLL patients (comparison MBL P=0.82) developed non
      hematologic cancer. On multivariable Cox regression analysis, individuals with
      high-count MBL had higher risk of non-hematologic cancer compared with flow
      controls (hazard ratio (HR)=2.36; P=0.04) and borderline higher risk compared
      with clinic controls (HR=2.00; P=0.07). Patients with high-count MBL appear to be
      at increased risk for non-hematologic cancer, further reinforcing that high-count
      MBL has a distinct clinical phenotype despite low risk of progression to CLL. 

PMID- 26310543
TI  - Seribantumab, an Anti-ERBB3 Antibody, Delays the Onset of Resistance and Restores
      Sensitivity to Letrozole in an Estrogen Receptor-Positive Breast Cancer Model.
AB  - Heregulin-driven ERBB3 signaling has been implicated as a mechanism of resistance
      to cytotoxic and antiendocrine therapies in preclinical breast cancer models. In
      this study, we evaluated the effects of seribantumab (MM-121), a heregulin
      blocking anti-ERBB3 monoclonal antibody, alone and in combination with the
      aromatase inhibitor letrozole, on cell signaling and tumor growth in a
      preclinical model of postmenopausal estrogen receptor-positive (ER(+)) breast
      cancer. In vitro, heregulin treatment induced estrogen receptor phosphorylation
      in MCF-7Ca cells, and long-term letrozole-treated (LTLT-Ca) cells had increased
      expression and activation levels of EGFR, HER2, and ERBB3. Treatment with
      seribantumab, but not letrozole, inhibited basal and heregulin-mediated ERBB
      receptor phosphorylation and downstream effector activation in letrozole
      sensitive (MCF-7Ca) and -refractory (LTLT-Ca) cells. Notably, in MCF-7Ca-derived
      xenograft tumors, cotreatment with seribantumab and letrozole had increased
      antitumor activity compared with letrozole alone, which was accompanied by
      downregulated PI3K/MTOR signaling both prior to and after the development of
      resistance to letrozole. Moreover, the addition of an MTOR inhibitor to this
      treatment regimen did not improve antitumor activity and was not well tolerated.
      Our results demonstrate that heregulin-driven ERBB3 signaling mediates resistance
      to letrozole in a preclinical model of ER(+) breast cancer, suggesting that
      heregulin-expressing ER(+) breast cancer patients may benefit from the addition
      of seribantumab to antiendocrine therapy.

PMID- 26310544
TI  - Recent Advances in Dendrimer Research for Cardiovascular Diseases.
AB  - Dendrimers, as a type of artificially synthesized polymers, have been
      increasingly attracting attention in many research fields, including the material
      and medical sciences, due to their unique characteristics that include their
      highly branched and well-defined molecular architecture, multivalency and tunable
      chemical compositions. These advantages make dendrimers potential carriers for
      the delivery of therapeutic and diagnostic agents. Herein, we review the recent
      advances in dendrimer research for the prevention and treatment of cardiovascular
      diseases, with special focus on their applications as carriers for drug and gene
      delivery, as contrast agents, and as potential new drugs. 

PMID- 26310545
TI  - Emergency department management of skin and soft tissue abscesses.

PMID- 26310546
TI  - Urinary nerve growth factor and a variable solifenacin dosage in patients with an
      overactive bladder.
AB  - INTRODUCTION AND HYPOTHESIS: We evaluated changes in urinary nerve growth factor
      (NGF) and NGF/creatinine (NGF/Cr) levels after increasing the dosage of
      solifenacin in overactive bladder patients. METHODS: The study groups included 59
      overactive bladder (OAB) patients and 20 healthy subjects as controls. We
      measured NGF at baseline for the patients and controls, and used the Overactive
      Bladder Awareness Tool (OAB-V8) to evaluate urinary symptoms. All patients
      received a treatment of solifenacin 5 mg for 6 weeks. The responders to treatment
      served as group 1 and nonresponders received solifenacin 10 mg for an additional
      6 weeks. Responders and nonresponders to the 10-mg treatment were defined as
      groups 2 and 3 respectively. NGF was measured after each treatment using the
      ELISA method and normalized by the urinary creatinine levels (NGF/Cr). RESULTS:
      There were 21, 22 and 16 patients in groups 1, 2, and 3 respectively. At
      baseline, the NGF and NGF/Cr levels were higher in groups 1, 2, and 3 compared
      with the controls. After the solifenacin 5 mg treatment, the NGF and NGF/Cr
      levels of group 1 individuals decreased to those of the control level. After
      increasing the dosage of solifenacin to 10 mg in group 2, the NGF and NGF/Cr
      levels decreased to normal levels. In group 3 (patients who did not responded to
      any treatment), these levels remained unchanged. CONCLUSIONS: Our results suggest
      that urinary NGF could be a potential biomarker for monitoring the treatment of
      symptoms in OAB patients who are treated with solifenacin.

PMID- 26310547
TI  - [The development history of the subspecialty of pediatric endocrinology and
      metabolism in China].

PMID- 26310548
TI  - [To further improve the diagnosis and management of central precocious puberty].

PMID- 26310549
TI  - [The future perspectives of clinical diagnosis and management of genetic
      diseases: lessons learned from the current status of Prader-Willi syndrome in
      China].

PMID- 26310550
TI  - [Consensus statement For the diagnosis and treatment of central precocious
      puberty (2015)].

PMID- 26310551
TI  - [Consensus on the diagnosis and treatment of Pediatric Prader-Willi syndrome
      (2015)].

PMID- 26310552
TI  - [Seven patients of argininemia with spastic tetraplegia as the first and major
      symptom and prenatal diagnosis of two fetuses with high risk].
AB  - OBJECTIVE: Argininemia is a rare disorder of urea cycle defect. The clinical
      manifestations of this disorder are similar to those of cerebral palsy so that
      the diagnosis is usually much delayed. This study aimed to investigate the
      phenotypes and genotypes of seven Chinese patients suffering from argininemia.
      METHOD: Three boys and four girls with spastic tetraplegia were diagnosed as
      argininemia by blood aminoacids analysis and ARG1 gene study. Patients were given
      a protein-restricted diet, citrulline, sodium benzoate, and other treatment
      intervention. The mother of Patient 5 and 6 accepted genetic counseling and
      underwent prenatal diagnosis by amniocentesis. RESULT: Seven patients presented
      with progressive spastic tetraplegia and poor physical growth from the age of 1
      month to 4 years. Argininemia was found at the age of 1 year and 10 months to 12
      years. Five patients had mental retardations. Three had seizures. Their blood
      arginine elevated (86.66 to 349.83 umol/L, normal controls 5 to 25 umol/L). Liver
      dysfunction was found in six patients. Five patients had elevated blood ammonia
      levels. In four patients, cerebral atrophy was observed by cranial magnetic
      resonance imaging. Nine mutations in the ARG1 gene were identified from 7
      patients. Only two mutations, c.703G > A in exon 7 and c.32T > C in exon 1 had
      been reported. c.34G > T, c.53G > A, c.67delG, c.232dupG, c.374C > T, c.539G > C
      and c.646-649delCTCA, were novel mutations of ARG1. A homozygous mutation c.703G
      > A was found in the amniocytes of Patient 5's mother, indicating that the fetus
      was affected by argininemia. Induced abortion was performed. c.53G > A from
      Patient 6 was not found in the amniocytes of her mother, indicating that the
      fetus was not affected by hepatocyte arginase deficiency. The result was
      confirmed by postnatal mutation analysis of cord blood and the normal blood
      arginine of the newborn. CONCLUSION: Argininemia is one of the few treatable
      causes of pediatric spastic paralysis. In this study, seven Chinese patients with
      spastic tetraplegia were detected by blood aminoacids analysis and confirmed by
      molecular analysis. Seven novel mutations on ARG1 gene were identified. Prenatal
      diagnosis of the fetus of a family was performed by amniocytes ARG1 gene
      analysis.

PMID- 26310553
TI  - [Clinical and genetic analysis for a Joubert syndrome family with CC2D2A gene
      mutations].
AB  - OBJECTIVE: To confirm the genetic diagnosis for providing services for genetic
      counseling and prenatal diagnosis, we analyzed the clinical and genetic data of a
      pedigree which is clinically diagnosed as Joubert syndrome. METHOD: A Joubert
      syndrome pedigree was enrolled as subject of this study from our hospital's
      outpatients in 2013. Following the medical history collection of the proband and
      the suffering fetus, target sequence capture and the next-generation sequencing
      technology were used for the proband and the suffering fetus to find the
      causative genes and sanger sequencing for the members of the pedigree to check
      and verify if the inherited mutations are in accordance with the Mendelian
      inheritance. Combining the clinical symptoms and signs with the total testing
      results, we analyzed the Joubert syndrome pedigree clinically and genetically.
      RESULT: The proband showed abnormal respiratory patterns (neonatal tachypnea) and
      hypertonia without abnormal eye movements, and reflected the molar tooth sign on
      the magnetic resonance imaging. And afterwards the patient developed hypotonia,
      ataxia, growth and intellectual disability accompanied by congenital
      blepharoptosis. There were no any symptoms and signs of liver, kidney and
      eyesight abnormalities so far. The affected fetus showed hydrocephalus by the
      auxiliary examination during the second trimesters of pregnancy without any
      appearance deformities. Both the proband and the affected fetus carried a
      missense mutation of CC2D2A gene c.2999A > T (p.Glu1000Val) from their father and
      carried the deletion of exon 20-21 on the same gene. Both variations were
      confirmed to be the Mendelian genetic compound heterozygous pattern. Whereas, the
      missense mutations c.2999A > T (p.Glu1000Val) on the CC2D2A gene have been proved
      to be inherited from the proband's father and the proband as well as the affected
      fetus. However, the proband's mother was normal at this locus of CC2D2A gene. The
      missense mutations c.2999A >T (p.Glu1000Val) have been confirmed to accord with
      Mendelian inheritance. CONCLUSION: The Joubert syndrome patient may show
      hypertonia in the early postnatal days as a result of hydrocephalus during the
      second and third trimesters of pregnancy besides manifesting hypotonia, ataxia,
      growth and intellectual disability markedly with age accompanied by the
      congenital blepharoptosis and revealing the molar tooth sign on the magnetic
      resonance imaging, considering the medical history and the whole testing results,
      the compound heterozygous mutations of c.2999A > T (p.Glu1000Val) and deletion of
      exon 20-21 of CC2D2A gene in the pedigree may be the causal gene mutations.

PMID- 26310554
TI  - [Analysis of clinical features of 6 patients with infantile type glycogen storage
      disease type II].
AB  - OBJECTIVE: To summarize clinical features and diagnosis of Chinese infantile
      patients with glycogen storage disease type II (GSD II). METHOD: Six infant
      patients with GSD II diagnosed from January 2012 to June 2014 in the Department
      of Pediatrics, Peking University First Hospital were enrolled into this study.
      Clinical information of the 6 patients, including clinical manifestation, blood
      biochemistry, chest X-ray, echocardiogram, electrocardiogram, acid alpha
      glucosidase (GAA) activity and GAA gene mutation analysis by direct sequencing of
      polymerase chain reaction (PCR) product were reviewed. RESULT: Of the 6 patients,
      five were female and one was male, five of whom were classic infantile type while
      the other one was atypical. The age of onset ranged from birth to 3-month-old.
      All patients had varying degrees of generalized muscle weakness, hypotonia and
      development retardation or retrogression. Other common findings were feeding
      difficulties in two patients, tongue weakness in two patients, respiratory
      distress in four patients, macroglossia in one patient, and hepatomegaly in two
      patients. Left ventricular hypertrophy and cardiomegaly were obvious in all the
      six patients. All six patients were found to have a enlarged heart in physical
      examination, and three patients who underwent a chest X-ray examination had an
      enlarged heart shadow. Four patients who had an echocardiography were found to
      have myocardial hypertrophy. The electrocardiogram in three patients showed short
      PR intervals and high voltage. The creatine kinase (CK) levels were three to
      seven times elevated. The mildest elevated CK was 441 IU/L, and the highest CK
      level was 1 238 U/L. Assay of GAA enzyme activity in whole blood showed
      significantly reduced activity (1.3 nmol/ (spot.d) to 2 nmol/(spot.d)) in the
      patients tested. Gene sequencing in 4 patients showed 8 pathogenic mutations,
      including 6 missense mutations, one nonsense mutation and one frameshift
      mutation. The missense mutations were c.998C > A (p.Thr333Lys), c.1280T > C
      (p.Met427Thr), c.1760T > C (p.Leu587Pro), c.1924G > T (p.Val642Phe), c.2012T > A
      (p.Met671Lys) and c.2105G > A (p.Arg702His). The nonsense mutation was c2662G > T
      (p.Glu888X), and the frameshift mutation was c2812_2813delTG (p.Cys938fs). The 5
      classic infantile patients died at the age of 7 to 22 months. The atypical
      infantile patient was 2 years and five months old according to our latest follow
      up. CONCLUSION: Infantile GSD II had similar motor manifestations and cardiac
      involvements, blood biochemical test, imaging findings, enzyme assays, though
      there were slight differences. The probability of GSD II should be taken into
      consideration if an infant has both muscular disease and cardiac involvement.

PMID- 26310555
TI  - [Longitudinal study on infantile nocturnal sleep-wake pattern developmental
      trajectory with Actiwatch].
AB  - OBJECTIVE: To understand the infantile nocturnal sleep-wake pattern developmental
      trajectory with Actiwatch, which would benefit the clinical assessment of
      infantile sleep. METHOD: This study was a longitudinal study conducted between 7
      Oct, 2009-30 Oct, 2011 in 10 hospitals of 9 cities of China ( Beijing, Xi'an,
      Qingdao, Wuhan, Changsha, Chongqing, Huzhou, Xiamen and Liuzhou). Actiwatch was
      used to track the sleep-wake pattern development trajectory of healthy infants in
      the first year of life in the home setting. Participating infants were followed
      up at 10th day and 28th day during the first month, and then monthly from the
      second to the sixth month after birth, and then at ninth and twelve months of age
      respectively. Meanwhile, infantile sleep was observed continuously for about 60
      hours at each visit. According to the characteristics of repeated measurement
      data of this study, two-level random effect model was adopted to analyze the
      trend of infantile nocturnal sleep-wake parameters changing with age, and the
      gender difference. RESULT: A total of 473 healthy infants were included in this
      study, among whom 246 (52.0%) were boys, and 227 (48.0%) were girls; 355 (75.1%)
      infants completed the whole year follow-up survey. With infants' age increasing,
      the latency of infants' nighttime sleep onset decreased from 66.8 minutes on 10th
      day to 15.5-18.7 minutes at 6-12 months of age. The number of night wakes also
      decreased with age, while uninterrupted sleep periods lengthened with age. On the
      10th day, there were 3.0 times of nightwaking on average, and the longest
      continuous sleeping interval lasted for 227.6 minutes on average. At 12-month of
      age, infants could sleep continuously for 350.9 minutes at most on average, while
      the number of nightwaking decreased to 1.6 times per night on average. Generally,
      nighttime sleep efficiency increased from 66.3% on the 10th day to 86.3% at 12
      month of age. The differences of sleep-wake patterns between boys and girls
      presented as boys' nocturnal longest uninterrupted sleep period was 19 minutes
      shorter(266.6 vs. 285.6 min), and the average nighttime sleep efficiency was 2.2%
      lower (74.2% vs. 76.4%) compared with girls respectively. And the differences of
      sleep efficiency between boys and girls reduced gradually along with the growth.
      CONCLUSION: During the first 6 months after birth, infantile sleep-wake pattern
      undergo obvious change. The capability of sleep-onset and uninterrupted sleep
      improved with age, and the sleep efficiency increased.

PMID- 26310556
TI  - [Suppressive effect of hydrogen sulfide donor on endothelin-1 production in aorta
      of atherosclerotic rats].
AB  - OBJECTIVE: To examine the effect of H2S donor, sodium hydrosulfide (NaHS), on ET
      1 level in plasma and aorta in rats with atherosclerosis (AS). METHOD: Thirty
      male rats, weighting 200-220 g, were randomly divided into AS, AS+NaHS and
      control groups, n = 10 in each group.Rats were given a single dose of vitamin D3
      (700 000 U/kg) in the first three days and fed with a high-cholesterol diet for 8
      weeks to induce AS. Rats in AS+NaHS group were intraperitoneally injected with an
      H2S donor NaHS, at a dose of 56 umol/(kg.d) for 8 weeks. At the end of the
      experiment for 8 weeks, all the rats were sacrificed. The plasma was collected
      and the aorta and coronary tissues were isolated. The atherosclerotic lesions in
      both aorta and coronary arteries were detected using oil red O method. H2S
      concentration in plasma was determined with sulfide-sensitive electrode method.
      ET-1 levels in plasma and aorta were calculated by radioimmunoassay kit and the
      localization of ET-1 in the aorta was detected by immunohistochemistry. Plasma
      nitric oxide synthase (NOS), endothelial NOS (eNOS), inducible NOS (iNOS) were
      detected with colorimetry. RESULT: AS plaque area in root of aorta of rats in AS
      group, AS+NaHS group and control group were (11.6+/-3.3)%, (1.6+/-1.1)%, (0.0+/
      0.1)% respectively. The difference in AS plaque area in root of aorta among the
      three groups was statistically significant (F=97.675, P < 0.05). AS plaque area
      in coronary artery of rats in AS group, AS+NaHS group and control group were
      (21.4+/-5.7)%, (4.8+/-2.5)%, (0.0+/-0.0)% respectively. The difference in AS
      plaque area in coronary artery among the three groups was statistically
      significant (F=97.519, P < 0.05). Plasma H2S level in rats of AS group ((22.0+/
      3.1) umol/L) was significantly lower than that of control group ((27.9+/-1.0)
      umol/L) and AS+NaHS group ((33.3+/-6.2) umol/L, all P < 0.05). Compared with
      control group ((70.0+/-10.7) ng/L), plasma ET-1 in rats of AS group ((89.6+/
      14.2) ng/L) and AS+NaHS group ((93.1+/-15.5) ng/L, P both < 0.05) were increased.
      However, there was no significant difference in plasma ET-1 content in rats
      between AS+NaHS group and AS group (P > 0.05). Compared with control group
      ((3.8+/-1.2) ng/g), ET-1 content in aorta in rats of AS group ((11.9+/-4.9) ng/g)
      and AS+NaHS group ((8.2+/-2.5) ng/g, both P < 0.05) were increased, and ET-1
      content in aorta in rats of AS+NaHS group was decreased compared with AS group (P
      < 0.05). Immunochemistry results showed that ET expression in cytoplasm in aortic
      endothelial cells in rats of AS group was strengthened, while ET expression in
      rats of control group and AS+NaHS group was weak. NOS activity of rats in control
      group, AS group and AS+NaHS group was (25.4+/-5.6), (51.8+/-10.0) and (27.6+/
      6.5) U/ml, eNOS activity (15.3+/-6.2), (4.5+/-2.7) and (8.7+/-3.9) U/ml, and iNOS
      activity (9.9+/-4.0), (47.3+/-10.7) and (19.0+/-5.2) U/ml,
      respectively.Differences among the three groups were statistically significant
      (NOS activity: F=37.231, P < 0.05, eNOS activity: F=14.600, P < 0.05, and iNOS
      activity: F=72.131, P < 0.05). CONCLUSION: H2S donor NaHS reduced the AS plaque
      in AS rats. The mechanisms might involve the protective effect of H2S on the
      vascular endothelial cell, decreasing ET-1 production in aortal endothelium of
      atherosclerotic rats.

PMID- 26310557
TI  - [Effects of urokinase type plasminogen activator and plasminogen activator
      inhibitor-1 expressions on the formation of aneurysm of perimembranous
      ventricular septal defect].
AB  - OBJECTIVE: The exact mechanisms of defect closure in patients with perimembranous
      ventricular septal defect (PMVSD) remain unknown. We hypothesized that the
      expression of urokinase type plasminogen activator (uPA) and plasminogen
      activator inhibitor-1 (PAI-1) may mediate extracellular matrix (ECM) remodeling
      in aneurysms. METHOD: Seven normal heart tricuspid septal leaflet and 33
      aneurysms were collected in Shanghai Renji Hospital and Shanghai Children's
      Medical Center from January 2008 to June 2010. Immunohistochemical expression of
      uPA and PAI-1 in 4 normal heart valvular tissues and 15 aneurysms was detected
      with immunohistochemical methods. The expression of uPA and PAI-1 mRNA in 3
      normal heart valvular tissues and 7 aneurysms was studied by real time
      fluorescent PCR; the protein expression of uPA and PAI-1 in 4 normal heart
      valvular tissues and 11 aneurysms was tested with Western blotting. RESULT: The
      surface of the aneurysms were completely covered by endothelial cells. Two types
      of granulation tissue, myxoid and fibrous, were associated with the aneurismal
      formation. uPA were recognized predominantly in valvar interstitial cells (VICs)
      which located mainly in regions adjacent to the endothelium and smooth muscle
      cells of blood vessels. PAI-1 was found in both VICs which located mainly in
      granulation tissue and endothelial cells. Nine aneurysms expressed a higher uPA
      activity than 4 normal valvular tissues ((74.6+/-11.8)% vs. (49.5+/-7.4)%; t =
      3.87, P = 0.003) and six aneurysms expressed a low uPA activity ((10.3+/-3.1)%
      vs. (49.5+/-7.4)%; t=11.78, P=0.000) and a high PAI-1 activity ((55.2+/-1.7)% vs.
      (50.8+/-3.8)%; t=2.55, P=0.034) using immunohistochemical methods. uPA / PAI-1
      ratio of protein expression tested by Western blot was 0.88+/-0.22 in four normal
      heart vavular tissues; five aneurysms expressed high uPA activity and low PAI-1
      activity and uPA/PAI-1 ratio was 4.26+/-2.04; while the other 6 cases expressed
      low uPA activity and high PAI-1 activity and uPA/PAI-1 ratio was 0.30+/-0.07; the
      difference among the three groups was statistically significant (P<0.05). The
      rate of uPA/PAI-1 in relative copy of mRNA expression among normal heart valvular
      tissue, high uPA expressed aneurysms and low uPA expressed aneurysms are also
      significantly different (2.14+/-0.17 vs. 0.45+/-0.04; 2.14+/-0.17 vs. 4.38+/
      1.41, P<0.05) respectively. CONCLUSION: The expression of uPA and PAI-1 in VICs
      suggests that interactions among these molecules contribute to the aneurysm
      formation and development. This provides a potential mechanism for defect closure
      in patients with PMVSD.

PMID- 26310558
TI  - [The etiological and clinical characteristics of hospitalized children with hand,
      foot and mouth disease in Beijing in 2013].
AB  - OBJECTIVE: To investigate the etiology of hand, foot and mouth disease (HFMD) in
      Beijing during 2013, and study the clinical characteristics of HFMD caused by the
      main serotypes of enterovirus in the study. METHOD: Clinical data and 128 stool
      samples were collected from 128 hospitalized children with HFMD in Beijing Ditan
      Hospital during 2013. One step RT-PCR method was used for enterovirus genotyping
      to investigate the etiology of HFMD. Clinical characteristics of HFMD caused by
      the main serotypes of enterovirus were analyzed. And VP1 segments of the main
      virus were amplified to construct phylogenetic tree for the phylogenetic
      analysis. RESULT: A total of 128 hospitalized children with HFMD were included.
      HFMD was more likely developed in children under 2 years of age (81.6%, 102/125);
      11 different enteroviruses were genotyped, with a total enterovirus positive rate
      of 76.6% (98/128); the positive rate of coxsackievirus A6 (CA6), 43.0% ( 55/128),
      was the highest, followed by enterovirus 71 (EV71), accounting for 14.8%
      (19/128). HFMD caused by CA6 was atypical, the rashes of which involved the
      perioral, trunk, limbs, face and neck (47%, 26/55), besides the common parts. Of
      the 55 cases caused by CA6, 6 children had clinical manifestations of nervous
      system involvement, one of whom even displayed type 2 respiratory failure. Mental
      status change more likely to occur in EV71-infected children than in CA6-infected
      ones (42% (8/19) vs. 11% (6/55) (chi(2)=7.041, P=0.008)); 13 children displayed
      onychomadesis, including 12 CA6 cases (23%, 12/53) and 1 CA10 cases (17%, 1/6),
      in the convalescence of hand, foot and mouth disease, and the correlation between
      onychomadesis and CA6 infection was significant (chi(2)=9.297, P=0.002).
      Phylogenetic analysis of 33 CA6 VP1 showed that the CA6 isolates of this study
      were highly similar to that of Taiwan and the nucleotide similarity was 95.91%
      98.89%. CONCLUSION: CA6 was the major pathogen of hospitalized children with
      hand, foot and mouth disease in Beijing during 2013, followed by EV71. The rashes
      caused by CA6 involved a wide range of skin sites and patients with CA6 infection
      displayed manifestations of neurological involvement or pulmonary edema similar
      to EV71 infection. Mental status change more likely occurred in EV71-infected
      children when neurological system was involved.?.

PMID- 26310559
TI  - [Six cases of Brucella infection in children and review of literatures].
AB  - OBJECTIVE: To present six cases of Brucella infection in children, analyze the
      characteristics of the disease, diagnostic and therapeutic process. METHOD: The
      clinical manifestations, laboratory test results and diagnostic process of 6
      confirmed cases of brucellosis seen between 2011-2012 were retrospectively
      analyzed and domestic and foreign literature was reviewed. RESULT: All the 6
      children had a history of either exposure to, travelling to endemic area, or
      consuming infected lamb/beef. After the relevant examinations for these children,
      either positive etiologic or serologic evidence of brucellosis infection was
      obtained. The main clinical manifestation was fever in all cases, the peak body
      temperature was 37.5-38.0  degrees C in 3 cases, 38.1-39.0  degrees C in 2 cases,
      39.1-41  degrees C in 1 case. Except for 1 case whose fever type was undulant
      fever, all the rest had irregular fever.Joint pain existed in 3 cases, orchitis
      in 1 case, cervical lymphadenopathy in 3 cases, hepatosplenomegaly in 2 cases,
      and impaired liver function in 4 cases. The Brucella agglutination test was
      positive in 5 cases. The blood culture was positive for all cases. In 4 cases the
      sulfamethoxazle and rifampicin were used for treatment, 1 case was treated with
      rifampicin and erythromycin, parents of 1 case refused to use the drug. The
      "brucellosis in children" was used to search literature at Wanfang database,
      Pubmed database for literature of recent 10 years, and a total of 13 articles
      including 15 cases were retrieved. All the patients had fever, 6 cases had joint
      swelling and pain, 10 cases had hepatosplenomegaly, 6 cases had cervical
      lymphadenopathy, 4 cases were complicated with central nervous system infection.
      Brucella agglutination test was positive in 9 cases and blood culture was
      positive for Brucella infection in all cases. CONCLUSION: Childhood Brucella
      infections are usually presented with various clinical manifestations, and are
      often accompanied by symptoms of systemic infection. For fever of unknown origin,
      one should include tests associated with brucellosis and pay special attention to
      differential diagnosis against other diseases.

PMID- 26310560
TI  - [Recent progress toward the diagnosis and clinical management of congenital
      hyperinsulinism].

PMID- 26310561
TI  - [Progress in diagnosis and treatment of cardiovascular syndromes with congenital
      heart disease in children].

PMID- 26310562
TI  - [Glucocorticoid therapy of progressive muscular dystrophy: the current state and
      progress].

PMID- 26310563
TI  - RNAi-mediated knockdown of vascular endothelial growth factor inhibits
      vascularization and tumor growth in renal cell carcinoma.
AB  - In the present study, we aimed to examine the effects of the knockdown of
      vascular endothelial growth factor (VEGF) by RNA interference (RNAi) on
      vascularization and tumor growth in renal cell carcinoma (RCC). For this purpose,
      a lentiviral vector expressing VEGF-shRNA was constructed and transfected into
      293T cells. The efficiency of RNAi was determined by infecting human 786-O RCC
      cells with viral particles and measuring the VEGF mRNA levels by reverse
      transcription-quantitative polymerase chain reaction (RT-qPCR). The effect of
      transfection with VEGF-shRNA on the secreted VEGF levels was also examined and
      the inhibitory effects on vascularization were also examined using a chick
      chorioallantoic membrane (CAM) assay. An RCC xenograft model was established in
      nude mice by implanting 786-O cells to form subcutaneous tumors. VEGF expression
      was observed by immunohistochemical (IHC) staining of the xenograft tumors. The
      tumor volume and tumor inhibition rate were also recorded. The apoptosis of the
      cancer cells was measured by TUNEL assay and the efficiency of tumor inhibition
      was estimated. The interference rate of VEGF-shRNA was 72.2% in the 786-O cells.
      Our results revealed that VEGF mRNA expression, the secreted VEGF level in the
      786-O cells and the total vessel length were markedly reduced in the VEGF-shRNA
      transfected cells compared with the controls (all P<0.05). Compared with the
      controls, injections of lentivirus expressing VEGF-shRNA significantly inhibited
      tumor growth, and reduced tumor mass and VEGF expression in the tumor tissue (all
      P<0.05). The apoptotic index in the treatment group was significantly higher than
      that in the controls (both P<0.05). Thus, our data indicate that the inhibition
      of VEGF expression by RNAi reduces VEGF mRNA levels, and inhibits angiogenesis
      and tumor growth in RCC, providing a future treatment option for RCC. 

PMID- 26310564
TI  - Hypothalamic Nesfatin-1 Stimulates Sympathetic Nerve Activity via Hypothalamic
      ERK Signaling.
AB  - Nesfatin-1 acts on the hypothalamus and regulates the autonomic nervous system.
      However, the hypothalamic mechanisms of nesfatin-1 on the autonomic nervous
      system are not well understood. In this study, we found that
      intracerebroventricular (ICV) administration of nesfatin-1 increased the
      extracellular signal-regulated kinase (ERK) activity in rats. Furthermore, the
      activity of sympathetic nerves, in the kidneys, liver, and white adipose tissue
      (WAT), and blood pressure was stimulated by the ICV injection of nesfatin-1, and
      these effects were abolished owing to pharmacological inhibition of ERK. Renal
      sympathoexcitatory and hypertensive effects were also observed with nesfatin-1
      microinjection into the paraventricular hypothalamic nucleus (PVN). Moreover,
      nesfatin-1 increased the number of phospho (p)-ERK1/2-positive neurons in the PVN
      and coexpression of the protein in neurons expressing corticotropin-releasing
      hormone (CRH). Pharmacological blockade of CRH signaling inhibited renal
      sympathetic and hypertensive responses to nesfatin-1. Finally, sympathetic
      stimulation of WAT and increased p-ERK1/2 levels in response to nesfatin-1 were
      preserved in obese animals such as rats that were fed a high-fat diet and leptin
      receptor-deficient Zucker fatty rats. These findings indicate that nesfatin-1
      regulates the autonomic nervous system through ERK signaling in PVN-CRH neurons
      to maintain cardiovascular function and that the antiobesity effect of nesfatin-1
      is mediated by hypothalamic ERK-dependent sympathoexcitation in obese animals. 

PMID- 26310565
TI  - Evaluation of the Correlation Between Childhood Asthma and Helicobacter pylori in
      Kashan.
AB  - BACKGROUND: Asthma is a chronic inflammatory air-way disease with increasing
      prevalence rate during the recent years. There are studies about the relationship
      between asthma and infectious diseases, including the association between asthma
      and Helicobacter pylori. According to the latest studies, there is an
      epidemiological correlation between asthma prevalence and prevalence of H.
      pylori. OBJECTIVES: The aim of this research was to study the correlation between
      H. pylori and asthma by biopsy in five to eighteen year-old children who had
      undergone endoscopy at Shahid Beheshti Hospital. PATIENTS AND METHODS: Three
      hundred children (5 to 18 years old) undergoing endoscopy owing to gastro
      intestinal problems at Shahid Beheshti Hospital were observed for childhood
      asthma using the Gina 2010 questionnaire which included 24 questions with "yes"
      and "no" answers to identify asthmatic patients with five positive answers. Next,
      the patients were referred to an allergy and asthma specialist for clinical
      examinations, spirometry and post bronchodilator test (Post BD). RESULTS: Among
      138 H. pylori positive patients, eight cases (5.8 %) were asthmatic while of the
      162 H. pylori negative patients 28 (17.3%) were asthmatic. This difference was
      statistically significant (P Value = 0.002). The correlation between H. pylori
      and asthma was studied after controlling the confounding variables including,
      gender, age and family history. The results obtained for the above-mentioned
      variables were significant (P Values of 0.004, 0.005 and 0.002, and Odd-Ratio
      Mantel Haenszel (ORMH) of 3.38, 3.24 and 4.06, respectively). CONCLUSIONS: Our
      findings showed that there is an inverse correlation between H. pylori and
      asthma. Performing more studies with larger sample sizes is necessary to confirm
      these results.

PMID- 26310566
TI  - Taping of the elbow extensor muscle in chronic stroke patients: comparison
      between before and after three-dimensional motion analysis.
AB  - [Purpose] This study aimed to observe the effect of kinesio taping on the quality
      of movement of each arm during a reaching task in patients with right-sided
      hemiparetic stroke. [Subjects and Methods] Sixteen right-handed participants who
      had had a right-sided hemiparetic stroke were requested to perform a reaching
      task with each arm, with and without kinesio taping. A three-dimensional motion
      analysis system was used to measure peak angular velocity, time to reach peak
      angular velocity, and movement units during elbow motion. [Results] In the right
      arm, movements during the reaching task with kinesio taping were faster,
      smoother, and more efficient than those without kinesio taping. The peak angular
      velocity increased, and the time to reach peak angular velocity decreased.
      Movement units decreased significantly. However, in the untaped arm, the movement
      was slower, rougher, and less efficient. [Conclusion] Kinesio taping provided a
      positive effect on the reaching movement of the taped arm of right-handed persons
      who had had a right-sided hemiparetic stroke. 

PMID- 26310567
TI  - Sequential Simulation (SqS): an innovative approach to educating GP receptionists
      about integrated care via a patient journey--a mixed methods approach.
AB  - BACKGROUND: An evaluation of an effective and engaging intervention for educating
      general practice (GP) receptionists about integrated care and the importance of
      their role within the whole system was conducted. METHODS: Workshops took place
      in North West London, one of England's 14 'Integrated Care Pioneers.' Three
      training days featuring Sequential Simulations (SqS) were held. Forty GP
      receptionists attended on each day, as well as 5-6 patients and 8-9 healthcare
      professionals. The SqS developed was from a collection of patient stories, the
      key scene of which featured a GP receptionist. The scenes were designed to show
      the consequences for the patient of professionals working in silos. This provided
      the focus for facilitated table discussions. The discussants suggested ways in
      which an unfortunate series of events could have been dealt with differently.
      These suggestions were then incorporated in a re-designed SqS. Evaluation was
      conducted through questionnaires, field notes and analysis of video material.
      Descriptive statistics and thematic analysis were applied. RESULTS: Ninety three
      participants responded to the questionnaire out of 131 attendees. All (93/93)
      respondents reported that the event was a powerful learning experience and that
      they had gained confidence in improving patient care. 98 % (91/93) reported that
      their knowledge of integrated care had improved. The simulation was rated highly
      as a learning experience [60 % (57/93) - excellent, 39 % (37/93) good]. Further
      evidence of educational benefit was expressed through comments such as: 'The
      simulations really got me thinking about the patient as a human with many
      problems and situations.' CONCLUSION: SqS is an innovative and practical way of
      presenting current care pathways and health care scenarios in order to create a
      shared focus, engage the emotions of the participants and bring the principles of
      integrated care to life. Facilitated table discussions are an opportunity to see
      events from multiple perspectives, share reactions and ideas, and practise co
      producing service reforms with patients. We believe this approach is a useful way
      of preparing front-line staff to participate in integrated care.

PMID- 26310568
TI  - Loss of tapasin correlates with diminished CD8(+) T-cell immunity and prognosis
      in colorectal cancer.
AB  - BACKGROUND: Tapasin is a crucial component of the major histocompatibility (MHC)
      class I antigen presentation pathway. Defects in this pathway can lead to tumor
      immune evasion. The aim of this study was to test whether tapasin expression
      correlates with CD8(+) cytotoxic T lymphocyte (CTL) infiltration of colorectal
      cancer (CRC) and overall survival. METHODS: A next-generation tissue microarray
      (ngTMA) of 198 CRC patients with full clinicopathological information was
      included in this study. TMA slides were immunostained for tapasin, MHC I and CD8.
      Marker expression was analyzed with immune-cell infiltration, patient survival
      and TNM-staging. RESULTS: A reduction of tapasin expression strongly correlated
      with venous invasion (AUC 0.682, OR 2.7, p = 0.002; 95% CI 1.7-5.0), lymphatic
      invasion (AUC 0.620, OR 2.0, p = 0.005; 95 % CI 1.3-3.3), distant metastasis (AUC
      0.727, OR 2.9, p = 0.004; 95% CI 1.4-5.9) and an infiltrative tumor border
      configuration (AUC 0.621, OR 2.2, p = 0.017; 95% CI 1.2-4.4). Further, tapasin
      expression was associated with CD8(+) CTL infiltration (AUC 0.729, OR 5.4, p <
      0.001; 95% CI 2.6-11), and favorable overall survival (p = 0.004, HR 0.6, 95% CI
      0.42-0.85). CONCLUSIONS: Consistent with published functional data showing that
      tapasin promotes antigen presentation, as well as tumor immune recognition and
      destruction by CD8(+) CTLs, a reduction in tapasin expression is associated with
      tumor progression in CRC.

PMID- 26310569
TI  - Nurses' accuracy and self-perceived ability using the Emergency Severity Index
      triage tool: a cross-sectional study in four Swiss hospitals.
AB  - BACKGROUND: The Emergency Severity Index (ESI) is an English language emergency
      department patient triage tool. After translation, it has been adapted for use to
      triage patients in growing numbers of emergency departments in non-English
      speaking countries. Few reports of the proficiency of triage nurses to score an
      ESI exist. We sought to determine accuracy, inter-rater reliability, and
      subjective confidence of triage nurses at four hospitals to determine an ESI from
      standardized ESI scenarios. METHODS: Triage nurses assigned an ESI score to each
      of 30 standard ESI (ESI Implementation Handbook Version 4) translated teaching
      case scenarios. Accuracy and Inter-rater reliability (Krippendorff's alpha) of
      the ESI scoring was measured. Nurses' subjective confidence applying the ESI
      algorithm was obtained by a Likert scale. RESULTS: Sixty-nine nurses from four
      EDs participated in the study. They scored 59.6 % of the case scenarios
      correctly. Inter-rater reliability was 0.78 (Krippendorff's alpha). Most (54/69,
      78 %) felt confident in their ability to apply the ESI. CONCLUSIONS: Low accuracy
      of ESI score assignment was observed when nurses scored an ESI for 30 standard
      written case scenarios, translated into nurses' native language, despite a good
      inter-rater reliability and high nurse confidence in their ability to apply the
      ESI. Although feasible, using standard written case scenarios to determine ESI
      triage scoring effectiveness may not be the optimum means to rate nurses' triage
      skills.

PMID- 26310570
TI  - Impact of Caregiver Type for 3-Year-Old Children on Subsequent Between-Meal
      Eating Habits and Being Overweight From Childhood to Adulthood: A 20-Year Follow
      up of the Ibaraki Children's Cohort (IBACHIL) Study.
AB  - BACKGROUND: Because of the increasing number of mothers who continue to work
      after childbirth, participation in childcare has diversified. However, the impact
      of the main caregiver on children's habits has not been determined. We sought to
      examine the effect of caregiver differences on childhood habituation of between
      meal eating and body mass index (BMI). METHODS: The Ibaraki Children's Cohort
      Study involved 4592 Japanese children whose parents answered health
      questionnaires at age 3. Follow-up questionnaires were distributed to parents
      when children were 6 and 12 years old and to study subjects directly when they
      were 22 years old. We compared prevalence of between-meal eating and overweight
      as well as mean BMI at ages 6, 12, and 22 years, by their main daytime caregiver
      at age 3. RESULTS: Compared to children cared for by mothers, those cared for by
      grandparents had a higher prevalence of between-meal eating before dinner for
      boys and girls at ages 6 and 12 years. At age 22 years, boys cared for by
      grandparents had a higher prevalence of overweight than those cared for by
      mothers (18.5% versus 11.2%, P = 0.037), but no such difference was noted in
      girls. However, both boys and girls cared for by grandparents had higher mean BMI
      over time than those cared for by mothers (coefficient = 0.47 kg/m(2) for boys
      and coefficient = 0.35 kg/m(2) for girls). CONCLUSIONS: Being cared for by
      grandparents at age 3 was associated with subsequent between-meal eating habits,
      being overweight, and increased mean BMI from childhood to adulthood.

PMID- 26310571
TI  - RNA sequencing from human neutrophils reveals distinct transcriptional
      differences associated with chronic inflammatory states.
AB  - BACKGROUND: The transcriptional complexity of mammalian cells suggests that they
      have broad abilities to respond to specific environmental stimuli and physiologic
      contexts. These abilities were not apparent a priori from the structure of
      mammalian genomes, but have been identified through detailed transcriptome
      analyses. In this study, we examined the transcriptomes of cells of the innate
      immune system, human neutrophils, using RNA sequencing (RNAseq). METHODS: We
      sequenced poly-A RNA from nine individual samples corresponding to specific
      phenotypes: three children with active, untreated juvenile idiopathic arthritis
      (JIA)(AD), three children with the same disease whose disease was inactive on
      medication (CRM), and three children with cystic fibrosis (CF). RESULTS: We
      demonstrate that transcriptomes of neutrophils, typically considered non-specific
      in their responses and functions, display considerable specificity in their
      transcriptional repertoires dependent on the pathologic context, and included
      genes, gene isoforms, and long non-coding RNA transcripts. Furthermore, despite
      the small sample numbers, these findings demonstrate the potential of RNAseq
      approaches to biomarker development in rheumatic diseases. CONCLUSIONS: These
      data demonstrate the capacity of cells previously considered non-specific in
      function to adapt their transcriptomes to specific biologic contexts. These data
      also provide insight into previously unrecognized pathological pathways and show
      considerable promise for elucidating disease and disease-state specific
      regulatory networks.

PMID- 26310572
TI  - Conformational heterogeneity of the Roc domains in C. tepidum Roc-COR and
      implications for human LRRK2 Parkinson mutations.
AB  - Ras of complex proteins (Roc) is a Ras-like GTP-binding domain that always occurs
      in tandem with the C-terminal of Roc (COR) domain and is found in bacteria,
      plants and animals. Recently, it has been shown that Roco proteins belong to the
      family of G-proteins activated by nucleotide (nt)-dependent dimerization (GADs).
      We investigated the RocCOR tandem from the bacteria Chlorobium tepidum with site
      directed spin labelling and pulse EPR distance measurements to follow
      conformational changes during the Roco G-protein cycle. Our results confirm that
      the COR domains are a stable dimerization device serving as a scaffold for the
      Roc domains that, in contrast, are structurally heterogeneous and dynamic
      entities. Contrary to other GAD proteins, we observed only minor structural
      alterations upon binding and hydrolysis of GTP, indicating significant
      mechanistic variations within this protein class. Mutations in the most prominent
      member of the Roco family of proteins, leucine-rich repeat (LRR) kinase 2
      (LRRK2), are the most frequent cause of late-onset Parkinson's disease (PD).
      Using a stable recombinant LRRK2 Roc-COR-kinase fragment we obtained detailed
      kinetic data for the G-protein cycle. Our data confirmed that dimerization is
      essential for efficient GTP hydrolysis and PD mutations in the Roc domain result
      in decreased GTPase activity. Previous data have shown that these LRRK2 PD
      mutations are located in the interface between Roc and COR. Importantly,
      analogous mutations in the conserved C. tepidum Roc/COR interface significantly
      influence the structure and nt-induced conformational changes of the Roc domains.

PMID- 26310573
TI  - PGC-1alpha limits angiotensin II-induced rat vascular smooth muscle cells
      proliferation via attenuating NOX1-mediated generation of reactive oxygen
      species.
AB  - AngII (angiotensin II)-induced excessive ROS (reactive oxygen species) generation
      and proliferation of VSMCs (vascular smooth muscle cells) is a critical
      contributor to the pathogenesis of atherosclerosis. PGC-1alpha [PPARgamma
      (peroxisome-proliferator-activated receptor gamma) co-activator-1alpha] is
      involved in the regulation of ROS generation, VSMC proliferation and energy
      metabolism. The aim of the present study was to investigate whether PGC-1alpha
      mediates AngII-induced ROS generation and VSMC hyperplasia. Our results showed
      that the protein content of PGC-1alpha was negatively correlated with an increase
      in cell proliferation and migration induced by AngII. Overexpression of PGC
      1alpha inhibited AngII-induced proliferation and migration, ROS generation and
      NADPH oxidase activity in VSMCs. Conversely, Ad-shPGC-1alpha (adenovirus-mediated
      PGC-1alpha-specific shRNA) led to the opposite effects. Furthermore, the
      stimulatory effect of Ad-shPGC-1alpha on VSMC proliferation was significantly
      attenuated by antioxidant and NADPH oxidase inhibitors. Analysis of several key
      subunits of NADPH oxidase (Rac1, p22(phox), p40(phox), p47(phox) and p67(phox))
      and mitochondrial ROS revealed that these mechanisms were not responsible for the
      observed effects of PGC-1alpha. However, we found that overexpression of PGC
      1alpha promoted NOX1 degradation through the proteasome degradation pathway under
      AngII stimulation and consequently attenuated NOX1 (NADPH oxidase 1) expression.
      These alterations underlie the inhibitory effect of PGC-1alpha on NADPH oxidase
      activity. Our data support a critical role for PGC-1alpha in the regulation of
      proliferation and migration of VSMCs, and provide a useful strategy to protect
      vessels against atherosclerosis.

PMID- 26310574
TI  - Folic acid promotes the myogenic differentiation of C2C12 murine myoblasts
      through the Akt signaling pathway.
AB  - Folic acid is a water-soluble vitamin in the B-complex group, and an exogenous
      intake is required for health, growth and development. As a precursor to co
      factors, folic acid is required for one-carbon donors in the synthesis of DNA
      bases and other essential biomolecules. A lack of dietary folic acid can lead to
      folic acid deficiency and can therefore result in several health problems,
      including macrocytic anemia, elevated plasma homocysteine levels, cardiovascular
      disease, birth defects, carcinogenesis, muscle weakness and difficulty in
      walking. Previous studies have indicated that folic acid exerts a positive effect
      on skeletal muscle functions. However, the precise role of folic acid in skeletal
      muscle cell differentiation remains poorly understood. Thus, in the present
      study, we examined the effects of folic acid on neo-myotube maturation and
      differentiation using C2C12 murine myoblasts. We found that folic acid promoted
      the formation of multinucleated myotubes, and increased the fusion index and
      creatine kinase (CK) activity in a concentration-dependent manner. In addition,
      western blot analysis revealed that the expression levels of the muscle-specific
      marker, myosin heavy chain (MyHC), as well as those of the myogenic regulatory
      factors (MRFs), MyoD and myogenin, were increased in the folic acid-treated
      myotubes during myogenic differentiation. Folic acid also promoted the activation
      of the Akt pathway, and this effect was inhibited by treatment of the C2C12 cells
      with LY294002 (Akt inhibitor). Blocking of the Akt pathway with a specific
      inhibitor revealed that it was necessary for mediating the stimulatory effects of
      folic acid on muscle cell differentiation and fusion. Taken together, our data
      suggest that folic acid promotes the differentiation of C2C12 cells through the
      activation of the Akt pathway. 

PMID- 26310575
TI  - Optical anisotropy and strong H-aggregation of poly(3-alkylthiophene) in a
      surface monolayer.
AB  - Slab optical waveguide absorption spectra reveal that surface segregated
      monolayers of a vertically oriented poly(3-buthylthiophene) derivative have large
      optical anisotropy, and that confinement of the polymer chains in the isolated
      monolayer causes strong H-aggregation. 

PMID- 26310576
TI  - Trichosporon inkin biofilms produce extracellular proteases and exhibit
      resistance to antifungals.
AB  - The aim of this study was to determine experimental conditions for in vitro
      biofilm formation of clinical isolates of Trichosporon inkin, an important
      opportunistic pathogen in immunocompromised patients. Biofilms were formed in
      microtitre plates in three different media (RPMI, Sabouraud and CLED), with
      inocula of 104, 105 or 106 cells ml- 1, at pH 5.5 and 7.0, and at 35 and 28 
      degrees C, under static and shaking conditions for 72 h. Growth kinetics of
      biofilms were evaluated at 6, 24, 48 and 72 h. Biofilm milieu analysis were
      assessed by counting viable cells and quantification of nucleic acids released
      into biofilm supernatants. Biofilms were also analysed for proteolytic activity
      and antifungal resistance against amphotericin B, caspofungin, fluconazole,
      itraconazole and voriconazole. Finally, ultrastructural characterization of
      biofilms formed in microtitre plates and catheter disks was performed by scanning
      electron microscopy. Greater biofilm formation was observed with a starter
      inoculum of 106 cells ml- 1, at pH 7.0 at 35  degrees C and 80 r.p.m., in both
      RPMI and Sabouraud media. Growth kinetics showed an increase in both viable cells
      and biomass with increasing incubation time, with maximum production at 48 h.
      Biofilms were able to disperse viable cells and nucleic acids into the
      supernatant throughout the developmental cycle. T. inkin biofilms produced more
      protease than planktonic cells and showed high tolerance to amphotericin B,
      caspofungin and azole derivatives. Mature biofilms were formed by different
      morphotypes, such as blastoconidia, arthroconidia and hyphae, in a strain
      specific manner. The present article details the multicellular lifestyle of T.
      inkin and provides perspectives for further research. 

PMID- 26310578
TI  - Pharmacological Treatment in Upper Gastrointestinal Bleeding.
AB  - Acute upper gastrointestinal bleeding (AUGIB) is a common medical emergency.
      Bleeding peptic ulcers account for the majority of causes in patients presenting
      with AUGIB, whereas variceal bleeding in cirrhotic patients represents a more
      severe form of bleeding. Endoscopic therapy is the mainstay of treatment in
      patients with active bleeding, as it achieves hemostasis and improves patient
      outcomes. Pharmacotherapy is an important adjunct to endoscopic hemostasis. In
      the management of patients with bleeding peptic ulcers, acid suppression after
      endoscopic hemostasis reduces rates of further bleeding and interventions. In
      patients with stable hemodynamics awaiting endoscopy, acid suppression starts
      ulcer healing and downstages stigmata of bleeding, thereby reducing the need for
      endoscopic therapy. In managing patients with variceal bleeding, early
      administration of vasoactive drugs lowers splanchnic blood flow, promotes
      hemostasis, and makes subsequent endoscopic treatment easier. The use of
      vasoactive agents and antibiotics have both been shown to reduce mortality. In
      this review article, strategies of acid suppression therapy for peptic ulcer
      bleeds, vasoactive agents, and antibiotics for variceal bleeding, together with
      recent evidence on the use of tranexamic acid in gastrointestinal bleeding, are
      discussed. 

PMID- 26310577
TI  - Study protocol: a randomized controlled trial investigating the effects of a
      psychosexual training program for adolescents with autism spectrum disorder.
AB  - BACKGROUND: Previous research shows that adolescents with autism spectrum
      disorder (ASD) run several risks in their psychosexual development and that these
      adolescents can have limited access to reliable information on puberty and
      sexuality, emphasizing the need for specific guidance of adolescents with ASD in
      their psychosexual development. Few studies have investigated the effects of
      psychosexual training programs for adolescents with ASD and to date no randomized
      controlled trials are available to study the effects of psychosexual
      interventions for this target group. METHODS/DESIGN: The randomized controlled
      trial (RCT) described in this study protocol aims to investigate the effects of
      the Tackling Teenage Training (TTT) program on the psychosexual development of
      adolescents with ASD. This parallel clinical trial, conducted in the South-West
      of the Netherlands, has a simple equal randomization design with an intervention
      and a waiting-list control condition. Two hundred adolescents and their parents
      participate in this study. We assess the participants in both conditions using
      self-report as well as parent-report questionnaires at three time points during 1
      year: at baseline (T1), post-treatment (T2), and for follow-up (T3). DISCUSSION:
      To our knowledge, the current study is the first that uses a randomized
      controlled design to study the effects of a psychosexual training program for
      adolescents with ASD. It has a number of methodological strengths, namely a large
      sample size, a wide range of functionally relevant outcome measures, the use of
      multiple informants, and a standardized research and intervention protocol. Also
      some limitations of the described study are identified, for instance not making a
      comparison between two treatment conditions, and no use of blinded observational
      measures to investigate the ecological validity of the research results. TRIAL
      REGISTRATION: Dutch Trial Register NTR2860. Registered on 20 April 2011.

PMID- 26310579
TI  - Blimp-1/PRDM1 regulates the transcription of human CS1 (SLAMF7) gene in NK and B
      cells.
AB  - CS1 (CRACC/CD319/SLAMF7) is a member of SLAM (Signaling Lymphocyte Activation
      Molecule) family receptors and is expressed on NK cells, a subset of CD8(+) T
      lymphocytes, activated monocytes, mature dendritic cells and activated B cells.
      In NK cells, CS1 signaling induces cytolytic function of NK cells against targets
      whereas in B cells CS1 induces proliferation and autocrine cytokine production.
      CS1 is upregulated in multiple myeloma cells and contributes to clonogenic growth
      and tumorigenicity. However, the mechanism of CS1 upregulation is unknown. In
      this study, we analyzed the transcriptional regulation of human CS1 gene in NK
      and B cells. The promoter region of CS1 contains a Blimp-1/PRDM1 binding site and
      relative luciferase activities of successive deletion mutants of CS1 promoter
      were different between Blimp-1/PRDM1-positive and Blimp-1/PRDM1-negative cells.
      Proximal region of CS1 promoter contains a CAAT box and atypical TATA-box that
      might result in common transcription initiation at -29 nucleotides upstream of
      the ATG translation start codon. Electrophoretic Mobility Shift Assay (EMSA) and
      Chromatin Immunoprecipitation (ChIP) assays revealed Blimp-1/PRDM1 binds to the
      CS1 promoter region. Mutating the Blimp-1/PRDM1 site at -750 to -746 decreased
      the transcriptional activity of CS1 promoter implicating a trans-activating
      function of Blimp-1/PRDM1 in human CS1 gene regulation. The finding that Blimp
      1/PRDM1 enhances transcription of CS1 gene in multiple myeloma cells may help in
      developing novel strategies for therapeutic intervention in multiple myeloma.

PMID- 26310580
TI  - Studying respiratory rhythm generation in a developing bird: Hatching a new
      experimental model using the classic in vitro brainstem-spinal cord preparation.
AB  - It has been more than thirty years since the in vitro brainstem-spinal cord
      preparation was first presented as a method to study automatic breathing
      behaviors in the neonatal rat. This straightforward preparation has led to an
      incredible burst of information about the location and coordination of several
      spontaneously active microcircuits that form the ventrolateral respiratory
      network of the brainstem. Despite these advances, our knowledge of the mechanisms
      that regulate central breathing behaviors is still incomplete. Investigations
      into the nature of spontaneous breathing rhythmicity have almost exclusively
      focused on mammals, and there is a need for comparative experimental models to
      evaluate several unresolved issues from a different perspective. With this in
      mind, we sought to develop a new avian in vitro model with the long term goal to
      better understand questions associated with the ontogeny of respiratory rhythm
      generation, neuroplasticity, and whether multiple, independent oscillators drive
      the major phases of breathing. The fact that birds develop in ovo provides
      unparalleled access to central neuronal networks throughout the prenatal period -
      from embryo to hatchling - that are free from confounding interactions with
      mother. Previous studies using in vitro avian models have been strictly limited
      to the early embryonic period. Consequently, the details and even the presence of
      brainstem derived breathing-related rhythmogenesis in birds have never been
      described. In the present study, we used the altricial zebra finch (Taeniopygia
      guttata) and show robust spontaneous motor outflow through cranial motor nerve
      IX, which is first detectable on embryonic day four and continues through
      prenatal and early postnatal development without interruption. We also show that
      brainstem oscillations change dramatically over the course of prenatal
      development, sometimes within hours, which suggests rapid maturational
      modifications in growth and connectivity. We propose that this experimental
      preparation will be useful for a variety of studies aimed at testing the
      biophysical and synaptic properties of neurons that participate in the unique
      spatiotemporal patterns of avian breathing behaviors, especially in the context
      of early development. 

PMID- 26310581
TI  - Functional interaction between COL4A1/COL4A2 and SMAD3 risk loci for coronary
      artery disease.
AB  - OBJECTIVE: The COL4A1/COL4A2 region on chromosome 13q34 is a highly replicated
      locus for coronary artery disease (CAD). In the normal arterial wall, type IV
      collagen acts to inhibit smooth muscle cell proliferation. Its production is in
      part a function of TGFbeta signaling, but the specific regulatory mechanisms,
      especially in humans, have not been defined. Our aim was to decipher TGFbeta
      signaling components important in the regulation of COL4A1 and COL4A2 and
      determine whether these components showed genetic interaction with the
      COL4A1/COL4A2 locus for CAD association. METHODS AND RESULTS: Experiments were
      performed in primary human aortic smooth muscle cells and HT1080 fibroblasts.
      Pharmacological inhibition of the TGFbeta1 receptor and subsequent SMAD protein
      phosphorylation by treatment with an ALK5 inhibitor prevented the increase in
      COL4A1/COL4A2 mRNA (p < 0.001) and protein expression in response to TGFbeta1
      stimulation. In contrast, inhibition of the non-canonical TGFbeta signaling
      pathways was without effect. siRNA mediated knockdown of SMAD3 and SMAD4
      abolished the stimulatory effects of TGFbeta1 on COL4A1/COL4A2 (p < 0.001)
      whereas SMAD2 knockdown had no effect. In luciferase reporter assays, neither
      SMAD3 overexpression nor TGFbeta1 treatment altered COL4A1 or COL4A2 promoter
      activity, supportive of more complex regulation of type IV collagen gene
      expression by the TGFbeta/SMAD3 signaling pathway. Epistasis analysis in 5 CAD
      case/control cohorts revealed that SMAD3 and COL4A1/COL4A2 display statistical
      interaction for CAD association. CONCLUSIONS: These findings demonstrate that
      SMAD3 is a necessary factor for TGFbeta-mediated stimulation of mRNA and protein
      expression of type IV collagen genes in human vascular smooth muscle cells.
      Epistasis analyses further supports the hypothesis that the SMAD3-dependent
      regulation of COL4A1/COL4A2 may be of functional significance for CAD
      pathogenesis.

PMID- 26310582
TI  - Diffusion-weighted imaging of breast tumours at 3 Tesla and 7 Tesla: a
      comparison.
AB  - OBJECTIVES: To compare bilateral diffusion-weighted MR imaging (DWI) at 3 T and 7
      T in the same breast tumour patients. METHODS: Twenty-eight patients were
      included in this IRB-approved study (mean age 56 +/- 16 years). Before contrast
      enhanced imaging, bilateral DWI with b = 0 and 850 s/mm(2) was performed in 2:56
      min (3 T) and 3:48 min (7 T), using readout-segmented echo planar imaging (rs
      EPI) with a 1.4 * 1.4 mm(2) (3 T)/0.9 * 0.9 mm(2) (7 T) in-plane resolution.
      Apparent diffusion coefficients (ADC), signal-to-noise (SNR) and contrast-to
      noise ratios (CNR) were assessed. RESULTS: Twenty-eight lesions were detected (18
      malignant, 10 benign). CNR and SNR were comparable at both field strengths (p >
      0.3). Mean ADC values at 7 T were 4-22% lower than at 3 T (p <= 0.03). An ADC
      threshold of 1.275 * 10(-3) mm(2)/s resulted in a diagnostic specificity of 90%
      at both field strengths. The sensitivity was 94% and 100% at 3 T and 7 T,
      respectively. CONCLUSION: 7-T DWI of the breast can be performed with 2.4-fold
      higher spatial resolution than 3 T, without significant differences in SNR if
      compared to 3 T. KEY POINTS: * 7 T provides a 2.4-fold higher resolution in
      breast DWI than 3 T * 7 T DWI has a high diagnostic accuracy comparable to that
      at 3 T * At 7 T malignant lesions had 22 % lower ADC than at 3 T (p < 0.001).

PMID- 26310583
TI  - Quantitative DCE-MRI for prediction of pathological complete response following
      neoadjuvant treatment for locally advanced breast cancer: the impact of breast
      cancer subtypes on the diagnostic accuracy.
AB  - OBJECTIVES: To assess whether DCE-MRI pharmacokinetic (PK) parameters obtained
      before and during chemotherapy can predict pathological complete response (pCR)
      differently for different breast cancer groups. METHODS: Eighty-four patients who
      received neoadjuvant chemotherapy for locally advanced breast cancer were
      retrospectively included. All patients underwent two DCE-MRI examinations, one
      before (EX1) and one during treatment (EX2). Tumours were classified into
      different breast cancer groups, namely triple negative (TNBC), HER2+ and ER+/HER2
      , and compared with the whole population (WP). PK parameters Ktrans and Ve were
      extracted using a two-compartment Tofts model. RESULTS: At EX1, Ktrans predicted
      pCR for WP and TNBC. At EX2, maximum diameter (Dmax) predicted pCR for WP and
      ER+/HER2-. Both PK parameters predicted pCR in WP and TNBC and only Ktrans for
      the HER2+. pCR was predicted from relative difference (EX1 - EX2)/EX1 of Dmax and
      both PK parameters in the WP group and only for Ve in the TNBC group. No PK
      parameter could predict response for ER+/HER-. ROC comparison between WP and
      breast cancer groups showed higher but not statistically significant values for
      TNBC for the prediction of pCR CONCLUSIONS: Quantitative DCE-MRI can better
      predict pCR after neoadjuvant treatment for TNBC but not for the ER+/HER2- group.
      KEY POINTS: * DCE-MRI-derived pharmacokinetic parameters can predict response
      status of neoadjuvant chemotherapy treatment. * Ktrans can better predict pCR for
      the triple negative group. * No pharmacokinetic parameter could predict response
      for the ER+/HER2- group.

PMID- 26310585
TI  - Different Neurologic Aspects of Nutritional B12 Deficiency in Infancy.
AB  - The objective of this study is to evaluate neurologic problems caused by
      nutritional vitamin B12 deficiency in infancy. Twenty-four cases between 2 and 18
      months of age with neurologic symptoms and/or signs and diagnosed as nutritional
      vitamin B12 deficiency were analyzed. The most common symptoms were developmental
      retardation, afebrile seizures, and involuntary movements. The mean vitamin B12
      levels were lower in patients with both neurologic and extraneurologic
      involvement when compared to those with only neurologic symptoms. All of the
      cases were treated with vitamin B12. In patients with severe deficiencies,
      involuntary movements were observed during vitamin B12 treatment using
      cyanocobalamin form. At the 1-year follow-up, all but 3 patients were considered
      neurodevelopmentally normal. The 3 patients that did not fully recover, on
      admission, had the lowest vitamin B12 levels. It is of great importance to
      prevent, diagnose, and treat vitamin B12 deficiency promptly to prevent the long
      term neurologic problems. 

PMID- 26310584
TI  - Assessment of normal left atrial appendage anatomy and function over gender and
      ages by dynamic cardiac CT.
AB  - OBJECTIVES: The aim of this study was to evaluate variations in anatomy and
      function according to age and gender using cardiac computed tomography (CT) in a
      large prospective cohort of healthy patients. BACKGROUND: The left atrial
      appendage (LAA) is considered the most frequent site of intracardiac thrombus
      formation. However, variations in normal in vivo anatomy and function according
      to age and gender remain largely unknown. METHODS: Three-dimensional (3D) cardiac
      reconstructions of the LAA were performed from CT scans of 193 consecutive
      patients. Parameters measured included LAA number of lobes, anatomical position
      of the LAA tip, angulation measured between the proximal and distal portions,
      minimum (iVolmin) and maximum (iVolmax) volumes indexed to body surface area
      (BSA), and ejection fraction (LAAEF). Relationship with age was assessed for each
      parameter. RESULTS: We found that men had longer and wider LAAs. The iVolmin and
      iVolmax increased by 0.23 and 0.19 ml per decade, respectively, while LAAEF
      decreased by 2% per decade in both sexes. CONCLUSIONS: Although LAA volumes
      increase, LAAEF decreases with age in both sexes. KEY POINTS: * Variations in
      normal left atrial appendage in vivo anatomy and function remain largely unknown.
      * Cardiac CT is reliable for left atrial appendage volume measurements. *
      Although LAA volumes increase, LAAEF decreases with age in both sexes.

PMID- 26310587
TI  - Methicillin-resistant Staphylococcus aureus: treatment with cultures of not drug
      resistant Staphylocuccus epidermidis.
AB  - The colonization and infection with methicillin-resistant Staphylococcus aureus
      is a major health problem in hospitals and long-term care facilities. Although
      bacteriaemias with MRSA (methicillin-resistant Staphylococcus aureus) can be
      treated with vancomycin and other reserve antibiotics, 20% of patients cannot be
      successfully cured. Inpatients colonized with MRSA are isolated in hospitals
      according to the guidelines of the Robert-Koch-Institute, althouth in long-term
      care facilities these patients are not urgently isolated. Active decolonization
      measures are taken to eradicate colonization with MRSA. In order to reduce MRSA
      colonization, it could be possible to administer cultures of Staphylococcus
      epidermidis which have no anbitiotic resistance, so that physiological genes
      could be conferred from Staphylococcus epidermis to MRSA bacteria.

PMID- 26310586
TI  - Combined oral contraceptives: the risk of myocardial infarction and ischemic
      stroke.
AB  - BACKGROUND: Combined oral contraceptives (COCs) have been associated with an
      increased risk of arterial thrombosis, i.e. myocardial infarction or ischemic
      stroke. However, as these diseases are rare in young women and as many types of
      combined oral contraception exist, the magnitude of the risk and the effect of
      different hormonal contents of COC preparations remain unclear. OBJECTIVES: To
      estimate the risk of myocardial infarction or ischemic stroke in users compared
      with non-users of different types, doses and generations of combined oral
      contraception. SEARCH METHODS: We searched electronic databases (MEDLINE (1966 to
      July 08, 2015), EMBASE (1980 to July 08, 2015), Popline (1970 to July 08, 2015)
      and LILACS (1985 to July 08, 2015) for eligible studies, without language
      restrictions. SELECTION CRITERIA: We included observational studies that
      recruited women in the reproductive age group (18 to 50 years) and compared the
      risk of myocardial infarction or ischemic stroke between users and non-users of
      COCs. DATA COLLECTION AND ANALYSIS: Two review authors independently selected
      relevant studies and extracted data. We pooled relative risks ()(combined odds
      ratios and one incidence rate ratio) and 95% confidence intervals (CIs) for
      myocardial infarction or ischemic stroke in users versus non-users of COCs.We
      combined the outcomes of myocardial infarction and ischemic stroke and also
      analysed these outcomes separately. Analyses were stratified according to
      estrogen dose and progestagen type. MAIN RESULTS: In total, we identified 1298
      publications through the search strategy. We included 28 publications reporting
      on 24 studies. COC users were at increased risk of myocardial infarction or
      ischemic stroke compared with non-users: relative risk (RR) 1.6 (95% CI 1.3
      1.9).These RRs were similar for myocardial infarction (1.6, 95% CI 1.2 to 2.1)
      and ischemic stroke (1.7, 95% CI 1.5 to 1.9). The risks did not vary clearly
      according to the generation of progestagen or according to progestagen type. When
      we stratified preparations according to estrogen dose, the risk of myocardial
      infarction or ischemic stroke seemed to increase with higher doses of estrogen.
      AUTHORS' CONCLUSIONS: This meta-analysis showed that the risk of myocardial
      infarction or ischemic stroke was 1.6-fold increased in women using COCs . The
      risk was highest for pills with > 50 microgram estrogen. When combined with the
      results of studies on the risk of venous thrombosis in COC users, it seems that
      the COC pill containing levonorgestrel and 30 MUg of estrogen is the safest oral
      form of hormonal contraception.

PMID- 26310588
TI  - Epicardial adipose tissue and coronary artery calcium predict incident myocardial
      infarction and death in HIV-infected patients.
AB  - BACKGROUND: Epicardial adipose tissue (EAT) and coronary artery calcium (CAC)
      have been associated with incident coronary artery disease (CAD) and all-cause
      mortality in the general population. Their prognostic impact in HIV is unknown.
      METHODS: Observational study of 843 consecutive HIV-infected patients receiving
      antiretroviral therapy for at least 6 months. Risk stratification was performed
      with coronary artery calcium (CAC) scoring and EAT screening. Patients were
      followed for CAD and all-cause mortality for a median of 2.8 years accounting for
      a total of 2572 patient-year follow-up. RESULTS: Mean patient age was 50 +/- 8
      years and 69% were men. At baseline EAT was associated with male gender, age,
      waist circumference, visceral adipose tissue, and lipodystrophy, while CAC score
      >= 100 was associated with male gender, age and total cholesterol. During follow
      up 33 patients suffered an event (15 incident myocardial infarctions and 18
      deaths); the EAT volume was larger and the CAC score was higher in patients with
      events (p = 0.038 and p = 0.001 respectively). Multivariable regression analyses
      demonstrated that the upper tertile of EAT (>= 93 cc; OR 2.15, 95% CI 1.06 -
      4.39, p = 0.034), and CAC score >= 100 (OR 3.37, 95% CI 1.49 - 7.60, p = 0.003)
      were independent predictors of events after adjusting for age and sex.
      CONCLUSIONS: In this observational cohort of HIV patients, EAT and CAC were
      independent predictors of hard outcomes after a median follow-up of approximately
      3 years.

PMID- 26310590
TI  - Early physical health conditions and school readiness skills in a prospective
      birth cohort of U.S. children.
AB  - RATIONALE: Extant research identifies associations between early physical health
      disparities and impaired functioning in adulthood, but limited research examines
      the emergence of these associations in the early years of children's lives.
      OBJECTIVE: This study draws on data from the Early Childhood Longitudinal Study
      Birth Cohort (ECLS-B; N = 5900) to assess whether a host of early health
      indicators measured from birth to age five are associated with children's
      cognitive and behavioral skills at age five. RESULTS: After adjusting for child
      and family characteristics, results revealed that children's neonatal risks
      (prematurity or low birth weight) and reports of poor health and hospitalizations
      were associated with lower cognitive skills, and neonatal risks and poor health
      predicted lower behavioral functioning at age five. Some of the association
      between neonatal risks and school readiness skills were indirect, functioning
      through children's poor health and hospitalization. Analyses further found that
      associations between early physical health and children's school readiness skills
      were consistent across subgroups defined by family income and child
      race/ethnicity, suggesting generalizability of results. CONCLUSIONS: Findings
      emphasize the need for more interdisciplinary research, practice, and policy
      related to optimizing child well-being across domains of physical health and
      development in the early years of life.

PMID- 26310589
TI  - Safety and efficiency of outpatient versus emergency department-based coronary CT
      angiography for evaluation of patients with potential ischemic chest pain.
AB  - BACKGROUND: While coronary CT angiography (coronary CTA) may be comparable to
      standard care in diagnosing acute coronary syndrome (ACS) in emergency department
      (ED) chest pain patients, it has traditionally been obtained prior to ED
      discharge and a strategy of delayed outpatient coronary CTA following an ED visit
      has not been evaluated. OBJECTIVE: To investigate the safety of discharging
      stable ED patients and obtaining outpatient CCTA. METHODS: At two urban Canadian
      EDs, patients up to 65 years with chest pain but no findings indicating presence
      of ACS were further evaluated depending upon time of presentation: (1) ED-based
      coronary CTA during normal working hours, (2) or outpatient coronary CTA within
      72 hours at other times. All data were collected prospectively. The primary
      outcome was the proportion of patients who had an outpatient coronary CTA ordered
      and had a predefined major adverse cardiac event (MACE) between ED discharge and
      outpatient CT; secondary outcome was the ED length of stay in both groups.
      RESULTS: From July 1, 2012 to June 30, 2014, we enrolled 521 consecutive
      patients: 350 with outpatient CT and 171 with ED-based CT. Demographics and risk
      factors were similar in both cohorts. No outpatient CT patients had a MACE prior
      to coronary CTA. (0.0%, 95% CI 0 to 0.9%) The median length of stay for ED-based
      evaluation was 6.6 hours (interquartile range 5.4 to 8.3 hours) while the
      outpatient group had a median length of stay of 7.0 hours (IQR 6.0 to 9.8 hours,
      n.s.). CONCLUSIONS: In ED chest pain patients with a low risk of ACS, performing
      coronary CTA as an outpatient may be a safe strategy.

PMID- 26310591
TI  - Children's self reported discomforts as participants in clinical research.
AB  - INTRODUCTION: There is little empirical evidence on children's subjective
      experiences of discomfort during clinical research procedures. Therefore,
      Institutional Review Boards have limited empirical information to guide their
      decision-making on discomforts for children in clinical research. To get more
      insight into what children's discomforts are during clinical research procedures,
      we interviewed a group of children on this topic and also asked for suggestions
      to reduce possible discomforts. MATERIALS AND METHODS: Forty-six children (aged 6
      18) participating in clinical research studies (including needle-related
      procedures, food provocation tests, MRI scans, pulmonary function tests,
      questionnaires) were interviewed about their experiences during the research
      procedures. Thematic analysis was used to analyze the interviews. RESULTS: The
      discomforts of the interviewed children could be divided into two main groups:
      physical and mental discomforts. The majority experienced physical discomforts
      during the research procedures: pain, shortness of breath, nausea, itchiness, and
      feeling hungry, which were often caused by needle procedures, some pulmonary
      procedures, and food provocation tests. Mental discomforts included anxiousness
      because of anticipated pain and not knowing what to expect from a research
      procedure, boredom and tiredness during lengthy research procedures and waiting,
      and embarrassment during Tanner staging. Children's suggestions to reduce the
      discomforts of the research procedures were providing distraction (e.g. watching
      a movie or listening to music), providing age-appropriate information and
      shortening the duration of lengthy procedures. DISCUSSION: Our study shows that
      children can experience various discomforts during research procedures, and it
      provides information about how these discomforts can be reduced according to
      them. Further research is needed with larger samples to study the number of
      children that experience these mentioned discomforts during research procedures
      in a quantitative way.

PMID- 26310592
TI  - The persistence of predictors of wellbeing among refugee youth eight years after
      resettlement in Melbourne, Australia.
AB  - This short report assesses the predictors of subjective health and happiness
      among a cohort of refugee youth over their first eight years in Australia. Five
      waves of data collection were conducted between 2004 (n = 120) and 2012-13 (n =
      51) using mixed methods. Previous schooling, self-esteem, moving house in the
      previous year, a supportive social environment, stronger ethnic identity and
      perceived discrimination were significant predictors of wellbeing after adjusting
      for demographic and pre-migration factors. When compared with a previous analysis
      of this cohort over their first three years of settlement, experiences of social
      exclusion still have a significant impact on wellbeing eight years after arriving
      in Australia. This study contributes to mounting evidence in support of policies
      that discourage discrimination and promote social inclusion and cultural
      diversity and which underpin the wellbeing of resettled refugee youth. 

PMID- 26310593
TI  - Which part of community social capital is related to life satisfaction and self
      rated health? A multilevel analysis based on a nationwide mail survey in Japan.
AB  - This paper aims to clarify the association between various social capital
      components at the municipal level (community social capital) and two quality-of
      life factors at the individual level [individual self-rated life satisfaction and
      self-rated health (SRH)] based on data from a nationwide social capital survey
      that the authors carried out in 2013 in Japan (N = 3406 in 99 municipalities).
      The survey covers residents in Japan between the ages of 20 and 79 years. We
      focus on both contextual social capital and household income inequality in terms
      of the Gini coefficient at the municipality level since, to the best of our
      knowledge, no paper has explicitly dealt with municipalities in Japan as the
      units of contextual social capital and the Gini. Our analyses show that the
      subjective life satisfaction of individuals, after controlling for socioeconomic
      status and health at the individual level, is associate with both an income gap
      and social capital at the municipal level. Every component of community social
      capital in this study except for generalized reciprocity, both cognitive
      (generalized trust, particularized trust, and particularized reciprocity), and
      structural (three types of group participation and daily contacts with neighbors,
      friends/acquaintances, and colleagues), and the Gini coefficient on earned income
      were associated with self-rated life satisfaction at the individual level with
      statistical significance. However, SRH is associated only with cognitive social
      capital at the community level. SRH has no significant association with
      structural components of community social capital or with a community income gap
      in terms of the Gini coefficient on personal income. Judging from the results of
      estimates in the study, most of the components of community social capital at the
      municipal level seem to play an important role in enhancing self-rated life
      satisfaction. Life satisfaction may be associated with the broad atmosphere of
      the municipal level where one resides, while SRH is associated with cognitive
      social capital rather than structural social capital. However, the difference in
      the impact of contextual social capital between the two QOL indices may indicate
      the importance of considering a proper contextual level that is suitable for the
      outcome. 

PMID- 26310594
TI  - The age profile of the location decision of Australian general practitioners.
AB  - The unbalanced distribution of general practitioners (GPs) across geographic
      areas has been acknowledged as a problem in many countries around the world.
      Quantitative information regarding GPs' location decision over their lifecycle is
      essential in developing effective initiatives to address the unbalanced
      distribution and retention of GPs. This paper describes the age profile of GPs'
      location decision and relates it to individual characteristics. I use the
      Medicine in Australia: Balancing Employment and Life (MABEL) survey of doctors
      (2008-2012) with a sample size of 5810 male and 5797 female GPs. I employ a mixed
      logit model to estimate GPs' location decision. The results suggest that younger
      GPs are more prepared to go to rural and remote areas but they tend to migrate
      back to urban areas as they age. Coming from a rural background increases the
      likelihood of choosing rural areas, but with heterogeneity: While male GPs from a
      rural background tend to stay in rural and remote areas regardless of age, female
      GPs from a rural background are willing to migrate to urban areas as they age.
      GPs who obtain basic medical degrees overseas are likely to move back to urban
      areas in the later stage of their careers. Completing a basic medical degree at
      an older age increases the likelihood of working outside major cities. I also
      examine factors influencing GPs' location transition patterns and the results
      further confirm the association of individual characteristics and GPs' location
      age profile. The findings can help target GPs who are most likely to practise and
      remain in rural and remote areas, and tailor policy initiatives to address the
      undesirable distribution and movement of GPs according to the identified
      heterogeneous age profile of their location decisions. 

PMID- 26310595
TI  - Induction, consolidation, and maintenance therapies with arsenic as a single
      agent for acute promyelocytic leukaemia in a 11-year follow-up.
AB  - The aim of this study was to evaluate the effect of arsenic trioxide as a single
      agent in acute promyelocytic leukaemia cases for induction, consolidation, and
      maintenance therapy in a long-term, 11-year follow-up. We studied 60 patients
      with acute promyelocytic leukaemia. Sixty percent of the patients were aged
      between 12 and 24 years. Arsenic trioxide was infused at a 0.15 mg/kg daily dose
      until complete remission was achieved. After 2 weeks of rest, arsenic trioxide
      was infused daily for 28 days as a consolidation therapy. Then, arsenic infusions
      were given every 3-4 months for 14 days for 2 years, and the patients were
      followed until relapse or death. The rates of complete remission, disease-free
      survival, overall survival, and drug toxicity were evaluated. The morphologic
      complete remission was observed in 55 out of the 60 patients. The most common
      causes of a remission failure were early mortality because of the APL
      differentiation syndrome and the lack of response to arsenic treatment. The mean
      follow-up was 90 months. The primary outcomes for males and females were a mean
      disease-free survival of 101 and 97 months, respectively, and a mean overall
      survival of 103 and 101 months, respectively. From the 55 cases with remission,
      three patients died (late mortality). Of the 60 patients, 85% are still alive.
      Arsenic trioxide was generally well tolerated. The long-term follow-up of
      patients with APL, treated with arsenic alone as induction, consolidation, and
      maintenance therapy, shows high cure rates and excellent outcomes. Copyright (c)
      2015 John Wiley & Sons, Ltd.

PMID- 26310596
TI  - Alcohol Use Predicts Number of Sexual Partners for Female but not Male STI Clinic
      Patients.
AB  - This study tested the hypothesis that greater alcohol involvement will predict
      number of sexual partners to a greater extent for women than for men, and that
      the hypothesized sex-specific, alcohol-sexual partner associations will hold when
      controlling for alternative sex-linked explanations (i.e., depression and drug
      use). We recruited 508 patients (46 % female, 67 % African American) from a
      public sexually transmitted infections (STI) clinic. Participants reported number
      of sexual partners, drinks per week, maximum drinks per day, frequency of heavy
      drinking; they also completed the AUDIT-C and a measure of alcohol problems. As
      expected, men reported more drinking and sexual partners. Also as expected, the
      association between alcohol use and number of partners was significant for women
      but not for men, and these associations were not explained by drug use or
      depression. A comprehensive prevention strategy for women attending STI clinics
      might include alcohol use reduction.

PMID- 26310597
TI  - Prospective study of patterns of surgical management in adults with primary
      cutaneous melanoma at high risk of spread, in Queensland, Australia.
AB  - BACKGROUND: Knowledge of variation in diagnosis and surgery in high-risk primary
      melanoma patients is limited. We assessed frequency and determinants of
      diagnostic procedures, wide local excision (WLE) and sentinel lymph node biopsy
      (SLNB). METHODS: People in Queensland newly diagnosed with melanoma, clinical
      stage 1b or 2, were recruited prospectively. Patient information was collected
      from questionnaires and pathology records. Differences in surgical procedures in
      relation to host and tumor characteristics were assessed. RESULTS: In 787
      participants, primary melanoma was diagnosed by surgical excision (74%), shave
      (14%), punch (12%) or incisional (1%) biopsy. General practitioners (GPs)
      diagnosed 80%. Diagnostic procedure differed by remoteness of residence, health
      sector, treating doctor's specialty and melanoma site and thickness. 766 patients
      had WLE, 86% by surgeons. Of 134 residual melanomas, 13 (10%) were <= 1 mm at
      diagnosis but > 1 mm at WLE, mostly after shave biopsy. SLNB was performed in 261
      (33%) patients. SLNB was more common in those under 50, in remoter locations or
      treated by GP initially, and less common with head and neck melanoma. CONCLUSION:
      Diagnostic and surgical procedures for primary melanoma vary substantially and
      partial biopsy can influence initial tumor microstaging. Patient, tumor and
      doctor characteristics influence SLNB practice.

PMID- 26310599
TI  - Intralocus sexual conflict, adaptive sex allocation, and the heritability of
      fitness.
AB  - Intralocus sexual conflict arises when selection favours alternative fitness
      optima in males and females. Unresolved conflict can create negative between-sex
      genetic correlations for fitness, such that high-fitness parents produce high
      fitness progeny of their same sex, but low-fitness progeny of the opposite sex.
      This cost of sexual conflict could be mitigated if high-fitness parents bias sex
      allocation to produce more offspring of their same sex. Previous studies of the
      brown anole lizard (Anolis sagrei) show that viability selection on body size is
      sexually antagonistic, favouring large males and smaller females. However, sexual
      conflict over body size may be partially mitigated by adaptive sex allocation:
      large males sire more sons than daughters, whereas small males sire more
      daughters than sons. We explored the evolutionary implications of these phenomena
      by assessing the additive genetic (co)variance of fitness within and between
      sexes in a wild population. We measured two components of fitness: viability of
      adults over the breeding season, and the number of their progeny that survived to
      sexual maturity, which includes components of parental reproductive success and
      offspring viability (RS(V) ). Viability of parents was not correlated with adult
      viability of their sons or daughters. RS(V) was positively correlated between
      sires and their offspring, but not between dams and their offspring. Neither
      component of fitness was significantly heritable, and neither exhibited negative
      between-sex genetic correlations that would indicate unresolved sexual conflict.
      Rather, our results are more consistent with predictions regarding adaptive sex
      allocation in that, as the number of sons produced by a sire increased, the adult
      viability of his male progeny increased. 

PMID- 26310600
TI  - Response to Braghiroli et al., regarding our study "Accuracy of a novel auto-CPAP
      device to evaluate the residual apnea-hypopnea index in patients with obstructive
      sleep apnea".

PMID- 26310601
TI  - Auto-CPAP: saving money as a single tool for OSA.

PMID- 26310602
TI  - Systematic analysis of the polyphenol metabolome using the Phenol-Explorer
      database.
AB  - SCOPE: The Phenol-Explorer web database details 383 polyphenol metabolites
      identified in human and animal biofluids from 221 publications. Here, we exploit
      these data to characterize and visualize the polyphenol metabolome, the set of
      all metabolites derived from phenolic food components. METHODS AND RESULTS:
      Qualitative and quantitative data on 383 polyphenol metabolites as described in
      424 human and animal intervention studies were systematically analyzed. Of these
      metabolites, 301 were identified without prior enzymatic hydrolysis of biofluids,
      and included glucuronide and sulfate esters, glycosides, aglycones, and O-methyl
      ethers. Around one-third of these compounds are also known as food constituents
      and corresponded to polyphenols absorbed without further metabolism. Many ring
      cleavage metabolites formed by gut microbiota were noted, mostly derived from
      hydroxycinnamates, flavanols, and flavonols. Median maximum plasma concentrations
      (C(max)) of all human metabolites were 0.09 and 0.32 MUM when consumed from foods
      or dietary supplements, respectively. Median time to reach maximum plasma
      concentration in humans (T(max)) was 2.18 h. CONCLUSION: These data show the
      complexity of the polyphenol metabolome and the need to take into account
      biotransformations to understand in vivo bioactivities and the role of dietary
      polyphenols in health and disease.

PMID- 26310603
TI  - Novel reporter system to monitor early stages of the hepatitis B virus life
      cycle.
AB  - A recombinant hepatitis B virus (HBV) expressing NanoLuc (NL) (HBV/NL) was
      produced by cotransfecting a plasmid containing a 1.2-fold HBV genome carrying
      the NL gene with a plasmid bearing a packaging-defective 1.2-fold HBV genome into
      a human hepatoma cell line, HepG2. We found that NL activity in HBV/NL-infected
      primary hepatocytes or sodium taurocholate cotransporting polypeptide-transduced
      human hepatocyte-derived cell lines increased linearly for several days after
      infection and was concordant with HBV RNA levels in the cells. Treatment of the
      virus-infected cells with HBV inhibitors reduced NL activity in a dose-dependent
      manner. Detection of HBV/NL infection, monitored by NL activity, was highly
      sensitive and less expensive than detection using the conventional method to
      evaluate HBV infection. In addition, because we also studied host factors, this
      system is applicable not only for studying the HBV life cycle, but also for
      exploring agent(s) that regulate HBV proliferation. 

PMID- 26310604
TI  - Benzylic Functionalization of Anthrones via the Asymmetric Ring Opening of
      Oxabicycles Utilizing a Fourth-Generation Rhodium Catalytic System.
AB  - While anthrones exist as privileged scaffolds in bioactive molecules, the
      enantioselective functionalization of anthrones is surprisingly scarce in the
      literature, with no asymmetric transition metal catalyzed example to date.
      Herein, we report the first asymmetric transition metal catalyzed benzylic
      functionalization of anthrones through the rhodium(I) catalyzed desymmetrization
      of oxabicycles. As previously developed rhodium(I) systems were found to be
      unsuitable for this substrate, a new robust fourth-generation [Rh(cod)OH]2 based
      catalytic system was developed to address synthetic challenges in this protocol. 

PMID- 26310605
TI  - Rapid detection of Bacillus anthracis by gamma phage amplification and lateral
      flow immunochromatography.
AB  - New, rapid point-of-need diagnostic methods for Bacillus anthracis detection can
      enhance civil and military responses to accidental or deliberate dispersal of
      anthrax as a biological weapon. Current laboratory-based methods for clinical
      identification of B. anthracis require 12 to 120h, and are confirmed by plaque
      assay using the well-characterized gamma typing phage, which requires an
      additional minimum of 24h for bacterial culture. To reduce testing time, the
      natural specificity of gamma phage amplification was investigated in combination
      with lateral flow immunochromatography (LFI) for rapid, point-of-need B.
      anthracis detection. Phage-based LFI detection of B. anthracis Sterne was
      validated over a range of bacterial and phage concentrations with optimal
      detection achieved in as little as 2h from the onset of amplification with a
      threshold sensitivity of 2.5*10(4)cfu/mL. The novel use of gamma phage
      amplification detected with a simple, inexpensive LFI assay provides a rapid,
      sensitive, highly accurate, and field-deployable method for diagnostic ID of B.
      anthracis in a fraction of the time required by conventional techniques, and
      without the need for extensive laboratory culture. 

PMID- 26310607
TI  - Kinetically Tunable Photostability of Fluorogen-Activating Peptide-Fluorogen
      Complexes.
AB  - Ease of genetic encoding, labeling specificity, and high photostability are the
      most sought after qualities in a fluorophore for biological detection.
      Furthermore, many applications can gain from the fluorogenic nature of
      fluoromodules and the ability to turn on the same fluoromodules multiple times.
      Fluorogen-activating peptides (FAPs) bind noncovalently to their cognate
      fluorogens and exhibit enhanced photostability. Herein, the photostabilities of
      malachite green (MG)-binding and thiazole-orange-binding FAPs are compared under
      limiting- and excess-fluorogen conditions to establish distinct mechanisms for
      photostability that correspond to the dissociation rate of the FAP-fluorogen
      complex. FAPs with slow dissociation show evidence of dye encapsulation and
      protection from photo or environmental degradation and single-step bleaching at
      the single molecule level, whereas those with rapid dissociation show repeated
      cycles of binding and enhanced photostability by exchange of bleached fluorogen
      with a new dye. A combination of generalizable selection pressure based on
      bleaching, flow cytometry, and site-specific amino acid mutagenesis is used to
      obtain a modified FAP with enhanced photostability, due to rapid dissociation of
      the MG fluorogen. These studies shed light on the basic mechanisms by which
      noncovalent association can effect photostable labeling, and demonstrate novel
      reagents for photostable and intermittent labeling of biological targets. 

PMID- 26310606
TI  - Quantitative proteomic analysis reveals maturation as a mechanism underlying
      glucocorticoid resistance in B lineage ALL and re-sensitization by JNK
      inhibition.
AB  - Glucocorticoid (GC) resistance is a continuing clinical problem in childhood
      acute lymphoblastic leukaemia (ALL) but the underlying mechanisms remain unclear.
      A proteomic approach was used to compare profiles of the B-lineage ALL GC
      sensitive cell line, PreB 697, and its GC-resistant sub-line, R3F9, pre- and post
      dexamethasone exposure. PAX5, a transcription factor critical to B-cell
      development was differentially regulated in the PreB 697 compared to the R3F9
      cell line in response to GC. PAX5 basal protein expression was less in R3F9
      compared to its GC-sensitive parent and confirmed to be lower in other GC
      resistant sub-lines of Pre B 697 and was associated with a decreased expression
      of the PAX5 transcriptional target, CD19. Gene set enrichment analysis showed
      that increasing GC-resistance was associated with differentiation from preB-II to
      an immature B-lymphocyte stage. GC-resistant sub-lines were shown to have higher
      levels of phosphorylated JNK compared to the parent line and JNK inhibition
      caused re-sensitization to GC. Exploiting this maturation may be key to
      overcoming GC resistance and targeting signalling pathways linked to the
      maturation state, such as JNK, may be a novel approach. 

PMID- 26310608
TI  - Strategies to improve BCG vaccine efficacy.

PMID- 26310609
TI  - Rare combination of congenital heart disease and pulmonary alveolar proteinosis.
AB  - Here, we describe a case of total anomalous pulmonary venous return with
      coarctation of the aorta that was diagnosed as pulmonary alveolar proteinosis at
      autopsy in a male infant. Surgical repair was performed at 1 day of age, but the
      infant died on postoperative day 51 due to respiratory insufficiency without any
      evidence of pulmonary venous obstruction. He had been unexpectedly diagnosed with
      pulmonary alveolar proteinosis and pulmonary hypoplasia on autopsy. Congenital
      pulmonary alveolar proteinosis is a serious condition with a high mortality rate,
      which should be considered in the differential diagnosis in patients with a
      clinical picture of pulmonary venous obstruction, because most patients are
      unable to survive without proper treatment. In this report, we address specific
      issues that should be discussed in such cases based on our recent experience.

PMID- 26310610
TI  - What Do We Learn from the Molecular Self-Assembly Process?

PMID- 26310611
TI  - Duelling 'CyanoHABs': unravelling the environmental drivers controlling dominance
      and succession among diazotrophic and non-N2 -fixing harmful cyanobacteria.
AB  - Eutrophication often manifests itself by increased frequencies and magnitudes of
      cyanobacterial harmful algal blooms (CyanoHABs) in freshwater systems. It is
      generally assumed that nitrogen-fixing cyanobacteria will dominate when nitrogen
      (N) is limiting and non-N2 fixers dominate when N is present in excess. However,
      this is rarely observed in temperate lakes, where N2 fixers often bloom when N is
      replete, and non-fixers (e.g. Microcystis) dominate when N concentrations are
      lowest. This review integrates observations from previous studies with insights
      into the environmental factors that select for CyanoHAB groups. This information
      may be used to predict how nutrient reduction strategies targeting N, phosphorus
      (P) or both N and P may alter cyanobacterial community composition. One
      underexplored concern is that as N inputs are reduced, CyanoHABs may switch from
      non-N2 fixing to diazotrophic taxa, with no net improvement in water quality.
      However, monitoring and experimental observations indicate that in eutrophic
      systems, minimizing both N and P loading will lead to the most significant
      reductions in total phytoplankton biomass without this shift occurring, because
      successional patterns appear to be strongly driven by physical factors, including
      temperature, irradiance and hydrology. Notably, water temperature is a primary
      driver of cyanobacterial community succession, with warming favouring non
      diazotrophic taxa. 

PMID- 26310612
TI  - Efficacy and safety of botulinum toxin type A for treatment of Frey's syndrome:
      evidence from 22 published articles.
AB  - Frey's syndrome (FS) is an unavoidable sequela following the surgery of the
      parotid gland. Although several treatment methods are available, their efficacy
      is short term or accompanied by unacceptable complications. In the past two
      decades, botulinum toxin type A (BTXA) has been widely used to treat FS. Although
      several systematic reviews have been reported recently, they were conflicting and
      with obvious deficiencies. Thus, we performed an objectively systematic review to
      determine whether BTXA is an effective and safe treatment for FS. A literature
      retrieval covering PubMed, Web of Science, Ovid, Embase and Cochrane library was
      performed on 16 January, 2015. Proportion meta-analysis and corresponding 95%
      confidence interval (CI) were performed to evaluate the efficacy and safety of
      BXTA in treatment of FS. A total of 499 records were retrieved and 22 articles
      with 23 studies were included after scrutiny by two independent authors.
      Statistical analyses regarding the effective rate, incidence of complications
      were used to estimate the efficacy and safety of BTXA. Our results suggested that
      the effective rate of BTXA for treatment of FS is 98.5% (95% CI = 0.971-0.994)
      and the incidence of complication is 3.6% (95% CI = 0.017-0.061). In conclusion,
      our study supports that BTXA produces meaningful benefits on the treatment of
      patients with FS. However, owing to lack of strong evidence, future studies with
      well-designed inclusion criteria and multicenter randomized controlled trials are
      needed to give more credible evidence, if possible.

PMID- 26310613
TI  - Resonance artefacts in modern pressure monitoring systems.
AB  - Resonance in pressure monitoring catheters is a well-known problem which was
      studied several years ago. Current piezoelectric devices have mechanical
      properties providing a resonance frequency and damping factor that theoretically
      assure resonance-free data. However, in particular cases, the coupling between
      the device, the catheter, and the vascular compliance of the patient could
      introduce artefacts in clinical settings leading to wrong pressure waveforms and
      values displayed in the monitor. In this research work we study a laboratory
      model of a clinical setting to evaluate in which cases the compound (catheter and
      device) could cause resonances in an unacceptable range. The classical pop-test
      is expanded for analysing the effect of the catheter. Results indicate that the
      presence of different catheters may alter significantly the acquired signal, up
      to an unacceptable level. Particular care should be used in the selection of the
      appropriate catheter. In particular, smaller diameters introduce higher damping
      coefficient that could help in avoiding undesired oscillations. 

PMID- 26310614
TI  - Potential analgesic effects of a novel N-acylethanolamine acid amidase inhibitor
      F96 through PPAR-alpha.
AB  - Pharmacological blockade of N-acylethanolamine acid amidase (NAAA) activity is an
      available approach for inflammation and pain control through restoring the
      ability of endogenous PEA. But the recently reported NAAA inhibitors suffer from
      the chemical and biological unstable properties, which restrict functions of NAAA
      inhibition in vivo. It is still unrevealed whether systematic inhibition of NAAA
      could modulate PEA-mediated pain signalings. Here we reported an oxazolidinone
      imide compound 3-(6-phenylhexanoyl) oxazolidin-2-one (F96), which potently and
      selectively inhibited NAAA activity (IC50 = 270 nM). Intraperitoneal (i.p.)
      injection of F96 (3-30 mg/kg) dose-dependently reduced ear edema and restored PEA
      levels of ear tissues in 12-O-Tetradecanoylphorbol-13-acetate (TPA) induced ear
      edema models. Furthermore, F96 inhibited acetic acid-induced writhing and
      increased spared nerve injury induced tactile allodynia thresholds in a dose
      dependent manner. Pharmacological effects of F96 (10 mg/kg, i.p.) on various
      animal models were abolished in PPAR-alpha(-/-) mice, and were prevented by PPAR
      alpha antagonist MK886 but not by canabinoid receptor type 1 (CB1) antagonist
      Rimonabant nor canabinoid receptor type 2 (CB2) antagonist SR144528. Zebrafish
      embryos experiments showed better security and lower toxicity for F96 than
      ibuprofen. These results revealed that F96 might be useful in treating
      inflammatory and neuropathic pain by NAAA inhibition depending on PPAR-alpha
      receptors. 

PMID- 26310615
TI  - Diagnosis and Management of Spinal Metastasis of Glioblastoma.
AB  - BACKGROUND: When patients with cranial glioblastoma develop weakness, a rare
      differential diagnosis is spinal metastases. METHODS: Chart and literature
      reviews were performed. RESULTS: The reported patient had delayed onset spinal
      drop metastasis that was only detected by magnetic resonance imaging (MRI). A 48
      year-old patient had supratentorial glioblastoma, treated with radiotherapy (RT)
      and concurrent temozolomide followed by six cycles of adjuvant temozolomide. Four
      years after completion of all treatments (62 months from initial presentation),
      he developed low backache and weakness in both legs. Positron emission
      tomography/computed tomography scans demonstrated intracranial recurrence only.
      Spinal drop metastases were detected only by MRI scan. Local spinal RT 40 Gy in
      20 fractions with concurrent and maintenance temozolomide were given. Because of
      disease progression after nine cycles of temozolomide, systemic therapy was
      changed to bevacizumab, which greatly improved his symptoms for 4 months before
      deterioration of mental status. He is still alive with disease at 22 months after
      diagnosis of spinal metastases (84 months from initial glioblastoma diagnosis).
      CONCLUSIONS: MRI is the diagnostic imaging of choice for spinal metastases. This
      illustrative case of delayed-onset spinal metastases shows unusual slow
      progression. Local RT, temozolomide, and targeted therapy may improve survival.
      This illustrative case is the first report of bevacizumab as a second-line
      therapy in drop metastasis of glioblastoma.

PMID- 26310617
TI  - Bioavailability Enhancement of Rizatriptan Benzoate by Oral Disintegrating Strip:
      In vitro and In vivo Evaluation.
AB  - Oral disintegrating strips containing rizatriptan benzoate, a selective 5-hydroxy
      tryptamine receptor agonist with anti migraine property, was developed using
      polyvinyl alcohol, sodium alginate and hydroxyl propyl methylcellulose as the
      base materials. The analytical and bioanalytical methods were developed and
      validated using HPLC (PDA and flouroscence detectors). The dissolution study
      performed on the strips revealed that all the five formulations, release the drug
      within eight minutes. Under ICH accelerated stability conditions, strips were
      stable at 40 degrees C and 75% humidity for eight weeks. Furthermore,
      pharmacokinetic properties of oral strip were compared with rizatriptan benzoate
      marketed tablet. Oral disintegrating strip and tablet showed significantly higher
      bioavailability. Oral strip exhibited better pharmacokinetic parameters than
      rizatriptan marketed tablet. The Tmax, Cmax, AUC and t1/2 for oral strip were
      found to be 1.00 h, 64.13+/-19.46 ng/mL, 352.00+/-71.57 ng/mL/h and 3.09+/-1.03 h
      respectively, whereas, tablet showed 1.5 h, 38.00+/-13.43 ng/mL, 210.38+/-
      40.37ng/mL/h and 1.66+/-0.31 h respectively. These findings confirm that the
      rizatriptan benzoate oral disintegrating strip is potentially a useful tool for
      an effective treatment of migraine with improved bioavailability, rapid onset of
      action and with increased patient compliance. 

PMID- 26310618
TI  - Targeting Mechanism of a Novel Liver-targeting Interferon IFN-CSP Involves Liver
      Heparan Sulfate Proteoglycan.
AB  - BACKGROUND: In our previous study, a novel liver-targeting interferon (IFN-CSP)
      combining IFN alpha2b with plasmodium region I-plus peptide was successfully
      designed and prepared with Escherichia coli expression systems. The purified IFN
      CSP showed anti-HBV activity and liver-targeting potentiality. The present
      investigation was designed to investigate the molecular mechanisms responsible
      for liver-targeting of IFN-CSP. METHODS: The binding site of IFN-CSP in
      hepatocytes was assayed by immunofluorescent staining. The correspondence of HSPG
      distribution and the pattern of IFN-CSP binding in liver tissue were determined
      using a confocal laser scanning microscope. Both the hepatocytes and liver tissue
      were using as model to investigate the effect of enzyme and soluble
      glycosaminoglycan on IFN-CSP binding using flow cytometry and fluorescence
      microscope. RESULTS: Studies of hepatocytes demonstrated that the localization of
      IFN-CSP in hepatocytes was the plasma membrane. Studies of liver tissue slices
      showed that IFN-CSP bound to liver tissue in a pattern similar to the
      distribution of heparan sulfate proteoglycan (HSPG) immunoreactivity.
      Pretreatment of hepatocytes and liver slices with heparinase reduced the binding
      of IFN-CSP to HepG2.2.15 cells and liver slices. Coincubation of IFN-CSP with
      heparin markedly inhibited IFNCSP binding to HepG2.2.15 cells and liver slices.
      CONCLUSION: These results indicate that the molecular mechanisms responsible for
      IFN-CSP targeting involve binding to HSPG of hepatocytes and liver.

PMID- 26310619
TI  - DEVELOPMENT AND CHARACTERIZATION OF GLUCOSE SENSITIVE HYDROGELS FOR THE TREATMENT
      OF DIABETES MELLIT.
AB  - Development of stimuli-sensitive hydrogels for the delivery of drug involves the
      development of matrices that are glucose-sensitive and have strong sensing
      properties so that the developed system can sense the level of glucose and
      release the medicament in response to blood glucose level. In the present study
      an attempt has been made to develop a glucose sensitive hydrogel system which
      modulates the release of an anti-diabetic drug in response to the blood glucose
      level in the body. The hydrogel system was prepared by gas foaming technique
      using chitosan and polyvinyl alcohol (PVA) as polymer and glutaraldehyde as cross
      linking agent. Metformin was used as a drug candidate because of its short
      biological half life (6.25+/-0.5 hrs). The prepared glucose sensitive hydrogel
      system has characterized using different parameters. It was observed that
      hydrogel swelled and deswelled reversibly depending on the pH and glucose
      sensitivity of the medium and has suitable mechanical properties. In-vitro
      results showed that the enzymatically immobilized hydrogel was sensitive to both
      pH and glucose for effective release of drug. It was found that higher the
      concentration of glucose in the medium, higher the amount of drug released from
      the hydrogel. In vivo results showed that glucose oxidase leads to reduction in
      blood glucose level in response to variable glucose concentration in the body
      thus achieving the desired therapeutic levels in the body . The present study
      showed that glucose sensitive hydrogels not only are efficient in controlling the
      physiological blood glucose level but also provide for a sustained and controlled
      release of drugs having short biological half life.

PMID- 26310616
TI  - Health-related quality of life in patients with pediatric onset of end-stage
      renal disease: state of the art and recommendations for clinical practice.
AB  - Health-related quality of life (HRQoL) is increasingly recognized as a key
      outcome in both clinical and research settings in the pediatric population with
      end-stage renal disease (ESRD). This review aims to: (1) summarize the current
      knowledge on HRQoL and socioprofessional outcomes and (2) provide strategies for
      incorporation of HRQoL assessment into clinical practice. Studies report that
      pediatric patients with ESRD have significantly lower HRQoL scores compared with
      children with other chronic diseases. Patients treated by dialysis are at
      particularly high risk for impaired HRQoL. Furthermore, patients more often have
      impaired neurocognitive functioning and lower academic achievement. Important
      determinants of impaired HRQoL include medical factors (i.e., receiving dialysis,
      disabling comorbidities, cosmetic side effects, stunted growth), sociodemographic
      factors (i.e., female gender, non-Western background) and psychosocial factors
      (i.e., noneffective coping strategies). Contrary to the situation in childhood,
      adult survivors of pediatric ESRD report a normal mental HRQoL. Despite this
      subjective feeling of well-being, these patients have on average experienced
      significantly more difficulties in completing their education, developing
      intimate relationships, and securing employment. Several medical and psychosocial
      strategies may potentially improve HRQoL in children with ESRD. Regular
      assessment of HRQoL and neurocognitive functioning in order to identify areas in
      which therapies and interventions may be required should be part of standard
      clinical care.

PMID- 26310620
TI  - Comparative Inhibition Study of Compounds Identified in the Methanolic Extract of
      Apamarga Kshara Against Trichomonas vaginalis Carbamate Kinase (TvCK): An
      Enzoinformatics Approach.
AB  - In the present study, we have identified ten compounds, namely dodecanol acid,
      myristic acid, neophytadiene, palmitic acid, heptadecanoic acid, linoleic acid,
      elaidic acid, 3-7-dimethyl acid, stearic acid and methyl eicos acid, of the
      methanolic extract of Apamarga Kshara by GC-MS analysis. Apamarga Kshara has been
      reported to be active against cervical erosion. Major causal organism for
      cervical erosion is Trichomonas vaginalis. However, there is a paucity of
      information about the mechanism of action and inhibitory effect of the
      biologically active natural compounds presented in A. Kshara against this
      organism (T. vaginalis). Therefore, present investigation was conducted to
      observe possible interactions of these compounds on T. vaginalis carbamate kinase
      using molecular docking software 'AutoDock 4.2.' Identification of the amino acid
      residues crucial for the interaction between T. vaginalis carbamate kinase and
      these natural compounds is of due scientific interest. The study will aid in
      efficacious and safe clinical use of the above-mentioned compounds.

PMID- 26310621
TI  - Administration of Tranexamic Acid Reduces Postoperative Blood Loss in Calcaneal
      Fractures: A Randomized Controlled Trial.
AB  - The present randomized controlled trial was undertaken to evaluate the effect of
      tranexamic acid (TXA) on reducing postoperative blood loss in calcaneal
      fractures. A total of 90 patients with a unilateral closed calcaneal fracture
      were randomized to the TXA (n = 45) and control (n = 45) groups. The
      corresponding groups received 15 mg/kg body weight of TXA or placebo (0.9% sodium
      chloride solution) intravenously before the skin incision was made. Open
      reduction and internal fixation was performed for all patients and selective bone
      grafting was performed. The patients were examined 3 months after surgery. The
      intraoperative and postoperative blood loss, blood test results, and wound
      complications were compared between the 2 groups. The complications of TXA were
      also investigated. No statistically significant differences were found in the
      baseline characteristics between the TXA and control groups. Also, no significant
      difference was noted in the intraoperative blood loss between the 2 groups.
      However, in the TXA group, the postoperative blood loss during the first 24 hours
      was significantly lower than that in the control group (110.0 +/- 160.0 mL versus
      320.0 +/- 360.0 mL; p < .001). The incidence of wound complications was also
      reduced compared with that in the control group (7.3% versus 23.8%; p = .036). No
      significant difference was found in the incidence of thromboembolic events or
      adverse drug reactions between the 2 groups. We concluded that preoperative
      single-dose TXA can effectively reduce postoperative blood loss and wound
      complications in patients with calcaneal fractures and that no significant side
      effects developed compared with the control group. 

PMID- 26310622
TI  - Synonymous variants in HTRA1 implicated in AMD susceptibility impair its capacity
      to regulate TGF-beta signaling.
AB  - High-temperature requirement A1 (HTRA1) is a secreted serine protease reported to
      play a role in the development of several cancers and neurodegenerative diseases.
      Still, the mechanism underlying the disease processes largely remains
      undetermined. In age-related macular degeneration (AMD), a common cause of vision
      impairment and blindness in industrialized societies, two synonymous
      polymorphisms (rs1049331:C>T, and rs2293870:G>T) in exon 1 of the HTRA1 gene were
      associated with a high risk to develop disease. Here, we show that the two
      polymorphisms result in a protein with altered thermophoretic properties upon
      heat-induced unfolding, trypsin accessibility and secretion behavior, suggesting
      unique structural features of the AMD-risk-associated HTRA1 protein. Applying
      MicroScale Thermophoresis and protease digestion analysis, we demonstrate direct
      binding and proteolysis of transforming growth factor beta1 (TGF-beta1) by normal
      HTRA1 but not the AMD-risk-associated isoform. As a consequence, both HTRA1
      isoforms strongly differed in their ability to control TGF-beta mediated
      signaling, as revealed by reporter assays targeting the TGF-beta1-induced serpin
      peptidase inhibitor (SERPINE1, alias PAI-1) promoter. In addition, structurally
      altered HTRA1 led to an impaired autocrine TGF-beta signaling in microglia, as
      measured by a strong down-regulation of downstream effectors of the TGF-beta
      cascade such as phosphorylated SMAD2 and PAI-1 expression. Taken together, our
      findings demonstrate the effects of two synonymous HTRA1 variants on protein
      structure and protein interaction with TGF-beta1. As a consequence, this leads to
      an impairment of TGF-beta signaling and microglial regulation. Functional
      implications of the altered properties on AMD pathogenesis remain to be
      clarified. 

PMID- 26310623
TI  - Intravitreal delivery of a novel AAV vector targets ON bipolar cells and restores
      visual function in a mouse model of complete congenital stationary night
      blindness.
AB  - Adeno-associated virus (AAV) effectively targets therapeutic genes to
      photoreceptors, pigment epithelia, Muller glia and ganglion cells of the retina.
      To date, no one has shown the ability to correct, with gene replacement, an
      inherent defect in bipolar cells (BCs), the excitatory interneurons of the
      retina. Targeting BCs with gene replacement has been difficult primarily due to
      the relative inaccessibility of BCs to standard AAV vectors. This approach would
      be useful for restoration of vision in patients with complete congenital
      stationary night blindness (CSNB1), where signaling through the ON BCs is
      eliminated due to mutations in their G-protein-coupled cascade genes. For
      example, the majority of CSNB1 patients carry a mutation in nyctalopin (NYX),
      which encodes a protein essential for proper localization of the TRPM1 cation
      channel required for ON BC light-evoked depolarization. As a group, CSNB1
      patients have a normal electroretinogram (ERG) a-wave, indicative of
      photoreceptor function, but lack a b-wave due to defects in ON BC signaling.
      Despite retinal dysfunction, the retinas of CSNB1 patients do not degenerate. The
      Nyx(nob) mouse model of CSNB1 faithfully mimics this phenotype. Here, we show
      that intravitreally injected, rationally designed AAV2(quadY-F+T-V) containing a
      novel 'Ple155' promoter drives either GFP or YFP_Nyx in postnatal Nyx(nob) mice.
      In treated Nyx(nob) retina, robust and targeted Nyx transgene expression in ON
      BCs partially restored the ERG b-wave and, at the cellular level, signaling in ON
      BCs. Our results support the potential for gene delivery to BCs and gene
      replacement therapy in human CSNB1. 

PMID- 26310624
TI  - Impaired hepcidin expression in alpha-1-antitrypsin deficiency associated with
      iron overload and progressive liver disease.
AB  - Liver disease due to alpha-1-antitrypsin deficiency (A1ATD) is associated with
      hepatic iron overload in a subgroup of patients. The underlying cause for this
      association is unknown. The aim of the present study was to define the genetics
      of this correlation and the effect of alpha-1-antitrypsin (A1AT) on the
      expression of the iron hormone hepcidin. Full exome and candidate gene sequencing
      were carried out in a family with A1ATD and hepatic iron overload. Regulation of
      hepcidin expression by A1AT was studied in primary murine hepatocytes. Cells co
      transfected with hemojuvelin (HJV) and matriptase-2 (MT-2) were used as a model
      to investigate the molecular mechanism of this regulation. Observed familial
      clustering of hepatic iron overload with A1ATD suggests a genetic cause, but
      genotypes known to be associated with hemochromatosis were absent. Individuals
      homozygous for the A1AT Z-allele with environmental or genetic risk factors such
      as steatosis or heterozygosity for the HAMP non-sense mutation p.Arg59* presented
      with severe hepatic siderosis. In hepatocytes, A1AT induced hepcidin mRNA
      expression in a dose-dependent manner. Experiments in overexpressing cells show
      that A1AT reduces cleavage of the hepcidin inducing bone morphogenetic protein co
      receptor HJV via inhibition of the membrane-bound serine protease MT-2. The acute
      phase protein A1AT is an inducer of hepcidin expression. Through this mechanism,
      A1ATD could be a trigger of hepatic iron overload in genetically predisposed
      individuals or patients with environmental risk factors for hepatic siderosis. 

PMID- 26310625
TI  - F-box protein 7 mutations promote protein aggregation in mitochondria and inhibit
      mitophagy.
AB  - The mutations of F-box protein 7 (FBXO7) gene (T22M, R378G and R498X) are
      associated with a severe form of autosomal recessive juvenile-onset Parkinson's
      disease (PD) (PARK 15). Here we demonstrated that wild-type (WT) FBXO7 is a
      stress response protein and it can play both cytoprotective and neurotoxic roles.
      The WT FBXO7 protein is vital to cell mitophagy and can facilitate mitophagy to
      protect cells, whereas mutant FBXO7 inhibits mitophagy. Upon stress, the
      endogenous WT FBXO7 gets up-regulated, concentrates into mitochondria and forms
      FBXO7 aggregates in mitochondria. However, FBXO7 mutations aggravate deleterious
      FBXO7 aggregation in mitochondria. The FBXO7 aggregation and toxicity can be
      alleviated by Proline, glutathione (GSH) and coenzyme Q10, whereas deleterious
      FBXO7 aggregation in mitochondria can be aggravated by prohibitin 1 (PHB1), a
      mitochondrial protease inhibitor. The overexpression of WT FBXO7 could lead to
      FBXO7 protein aggregation and dopamine neuron degeneration in transgenic
      Drosophila heads. The elevated FBXO7 expression and aggregation were identified
      in human fibroblast cells from PD patients. FBXO7 can also form aggregates in
      brains of PD and Alzheimer's disease. Our study provides novel pathophysiologic
      insights and suggests that FBXO7 may be a potential therapeutic target in FBXO7
      linked neuron degeneration in PD. 

PMID- 26310626
TI  - A novel mouse model for ataxia-telangiectasia with a N-terminal mutation displays
      a behavioral defect and a low incidence of lymphoma but no increased oxidative
      burden.
AB  - Ataxia-telangiectasia (A-T) is a rare multi-system disorder caused by mutations
      in the ATM gene. Significant heterogeneity exists in the underlying genetic
      mutations and clinical phenotypes. A number of mouse models have been generated
      that harbor mutations in the distal region of the gene, and a recent study
      suggests the presence of residual ATM protein in the brain of one such model.
      These mice recapitulate many of the characteristics of A-T seen in humans, with
      the notable exception of neurodegeneration. In order to study how an N-terminal
      mutation affects the disease phenotype, we generated an inducible Atm mutant
      mouse model (Atm(tm1Mmpl/tm1Mmpl), referred to as A-T [M]) predicted to express
      only the first 62 amino acids of Atm. Cells derived from A-T [M] mutant mice
      exhibited reduced cellular proliferation and an altered DNA damage response, but
      surprisingly, showed no evidence of an oxidative imbalance. Examination of the A
      T [M] animals revealed an altered immunophenotype consistent with A-T. In
      contrast to mice harboring C-terminal Atm mutations that disproportionately
      develop thymic lymphomas, A-T [M] mice developed lymphoma at a similar rate as
      human A-T patients. Morphological analyses of A-T [M] cerebella revealed no
      substantial cellular defects, similar to other models of A-T, although mice
      display behavioral defects consistent with cerebellar dysfunction. Overall, these
      results suggest that loss of Atm is not necessarily associated with an oxidized
      phenotype as has been previously proposed and that loss of ATM protein is not
      sufficient to induce cerebellar degeneration in mice. 

PMID- 26310627
TI  - A Rich-Club Organization in Brain Ischemia Protein Interaction Network.
AB  - Ischemic stroke involves multiple pathophysiological mechanisms with complex
      interactions. Efforts to decipher those mechanisms and understand the evolution
      of cerebral injury is key for developing successful interventions. In an
      innovative approach, we use literature mining, natural language processing and
      systems biology tools to construct, annotate and curate a brain ischemia
      interactome. The curated interactome includes proteins that are deregulated after
      cerebral ischemia in human and experimental stroke. Network analysis of the
      interactome revealed a rich-club organization indicating the presence of a
      densely interconnected hub structure of prominent contributors to disease
      pathogenesis. Functional annotation of the interactome uncovered prominent
      pathways and highlighted the critical role of the complement and coagulation
      cascade in the initiation and amplification of injury starting by activation of
      the rich-club. We performed an in-silico screen for putative interventions that
      have pleiotropic effects on rich-club components and we identified estrogen as a
      prominent candidate. Our findings show that complex network analysis of disease
      related interactomes may lead to a better understanding of pathogenic mechanisms
      and provide cost-effective and mechanism-based discovery of candidate
      therapeutics. 

PMID- 26310628
TI  - Genotype-phenotype characteristics and baseline natural history of heritable
      neuropathies caused by mutations in the MPZ gene.
AB  - We aimed to characterize genotype-phenotype correlations and establish baseline
      clinical data for peripheral neuropathies caused by mutations in the myelin
      protein zero (MPZ) gene. MPZ mutations are the second leading cause of Charcot
      Marie-Tooth disease type 1. Recent research makes clinical trials for patients
      with MPZ mutations a realistic possibility. However, the clinical severity varies
      with different mutations and natural history data on progression is sparse. We
      present cross-sectional data to begin to define the phenotypic spectrum and
      clinical baseline of patients with these mutations. A cohort of patients with MPZ
      gene mutations was identified in 13 centres of the Inherited Neuropathies
      Consortium - Rare Disease Clinical Research Consortium (INC-RDCRC) between 2009
      and 2012 and at Wayne State University between 1996 and 2009. Patient phenotypes
      were quantified by the Charcot-Marie-Tooth disease neuropathy score version 1 or
      2 and the Charcot-Marie-Tooth disease paediatric scale outcome instruments.
      Genetic testing was performed in all patients and/or in first- or second-degree
      relatives to document mutation in MPZ gene indicating diagnosis of Charcot-Marie
      Tooth disease type 1B. There were 103 patients from 71 families with 47 different
      MPZ mutations with a mean age of 40 years (range 3-84 years). Patients and
      mutations were separated into infantile, childhood and adult-onset groups. The
      infantile onset group had higher Charcot-Marie-Tooth disease neuropathy score
      version 1 or 2 and slower nerve conductions than the other groups, and severity
      increased with age. Twenty-three patients had no family history of Charcot-Marie
      Tooth disease. Sixty-one patients wore foot/ankle orthoses, 19 required walking
      assistance or support, and 10 required wheelchairs. There was hearing loss in 21
      and scoliosis in 17. Forty-two patients did not begin walking until after 15
      months of age. Half of the infantile onset patients then required ambulation aids
      or wheelchairs for ambulation. Our results demonstrate that virtually all MPZ
      mutations are associated with specific phenotypes. Early onset (infantile and
      childhood) phenotypes likely represent developmentally impaired myelination,
      whereas the adult-onset phenotype reflects axonal degeneration without antecedent
      demyelination. Data from this cohort of patients will provide the baseline data
      necessary for clinical trials of patients with Charcot-Marie-Tooth disease caused
      by MPZ gene mutations. 

PMID- 26310629
TI  - Chronic Activation of Innate Immunity Correlates With Poor Prognosis in Cancer
      Patients Treated With Oncolytic Adenovirus.
AB  - Despite many clinical trials conducted with oncolytic viruses, the exact tumor
      level mechanisms affecting therapeutic efficacy have not been established.
      Currently there are no biomarkers available that would predict the clinical
      outcome to any oncolytic virus. To assess the baseline immunological phenotype
      and find potential prognostic biomarkers, we monitored mRNA expression levels in
      31 tumor biopsy or fluid samples from 27 patients treated with oncolytic
      adenovirus. Additionally, protein expression was studied from 19 biopsies using
      immunohistochemical staining. We found highly significant changes in several
      signaling pathways and genes associated with immune responses, such as B-cell
      receptor signaling (P < 0.001), granulocyte macrophage colony-stimulating factor
      (GM-CSF) signaling (P < 0.001), and leukocyte extravasation signaling (P <
      0.001), in patients surviving a shorter time than their controls. In
      immunohistochemical analysis, markers CD4 and CD163 were significantly elevated
      (P = 0.020 and P = 0.016 respectively), in patients with shorter than expected
      survival. Interestingly, T-cell exhaustion marker TIM-3 was also found to be
      significantly upregulated (P = 0.006) in patients with poor prognosis.
      Collectively, these data suggest that activation of several functions of the
      innate immunity before treatment is associated with inferior survival in patients
      treated with oncolytic adenovirus. Conversely, lack of chronic innate
      inflammation at baseline may predict improved treatment outcome, as suggested by
      good overall prognosis. 

PMID- 26310630
TI  - Combination Therapy With Reovirus and Anti-PD-1 Blockade Controls Tumor Growth
      Through Innate and Adaptive Immune Responses.
AB  - Oncolytic reovirus can be delivered both systemically and intratumorally, in both
      preclinical models and in early phase clinical trials. Reovirus has direct
      oncolytic activity against a variety of tumor types and antitumor activity is
      directly associated with immune activation by virus replication in tumors. Immune
      mechanisms of therapy include both innate immune activation against virally
      infected tumor cells, and the generation of adaptive antitumor immune responses
      as a result of in vivo priming against tumor-associated antigens. We tested the
      combination of local oncolytic reovirus therapy with systemic immune checkpoint
      inhibition. We show that treatment of subcutaneous B16 melanomas with a
      combination of intravenous (i.v.) anti-PD-1 antibody and intratumoral (i.t.)
      reovirus significantly enhanced survival of mice compared to i.t. reovirus (P <
      0.01) or anti-PD-1 therapy alone. In vitro immune analysis demonstrated that
      checkpoint inhibition improved the ability of NK cells to kill reovirus-infected
      tumor cells, reduced T(reg) activity, and increased the adaptive CD8(+) T-cell
      dependent antitumor T-cell response. PD-1 blockade also enhanced the antiviral
      immune response but through effector mechanisms which overlapped with but also
      differed from those affecting the antitumor response. Therefore, combination with
      checkpoint inhibition represents a readily translatable next step in the clinical
      development of reovirus viroimmunotherapy.

PMID- 26310631
TI  - Inhibition of Aggregation of Mutant Huntingtin by Nucleic Acid Aptamers In Vitro
      and in a Yeast Model of Huntington's Disease.
AB  - Elongated polyglutamine stretch in mutant huntingtin (mhtt) correlates well with
      the pathology of Huntington's disease (HD). Inhibition of aggregation of mhtt is
      a promising strategy to arrest disease progression. In this work, specific, high
      affinity RNA aptamers were selected against monomeric mhtt (51Q-htt). Some of
      them inhibited its aggregation in vitro by stabilizing the monomer. They also
      recognized 103Q-htt but not 20Q-htt (nonpathogenic length). Inhibition of
      aggregation corresponded with reduced leakage of a fluorescent probe from
      liposomes and diminished oxidative stress in RBCs. The presence of aptamers was
      able to rescue the sequestration of the glycolytic enzyme glyceraldehyde-3
      phosphate dehydrogenase (GAPDH) by aggregated mhtt. Some of the aptamers were
      able to enhance the partitioning of mhtt in the soluble fraction in a yeast model
      of HD. They were also able to rescue endocytotic defect due to aggregation of
      mhtt. The beneficial effect of a combination of aptamers was enhanced with
      improvement in cell survival. Since HD is a monogenic autosomal dominant
      disorder, aptamers may be developed as a viable strategy to slow down the
      progress of the disease. Since they are nonimmunogenic and nontoxic, aptamers may
      emerge as strong candidates to reduce protein-protein interaction and hence
      protein aggregation in protein misfolding disorders in general. 

PMID- 26310632
TI  - A biospectroscopic analysis of human prostate tissue obtained from different time
      periods points to a trans-generational alteration in spectral phenotype.
AB  - Prostate cancer is the most commonly-diagnosed malignancy in males worldwide;
      however, there is marked geographic variation in incidence that may be associated
      with a Westernised lifestyle. We set out to determine whether attenuated total
      reflection Fourier-transform infrared (ATR-FTIR) or Raman spectroscopy combined
      with principal component analysis-linear discriminant analysis or variable
      selection techniques employing genetic algorithm or successive projection
      algorithm could be utilised to explore differences between prostate tissues from
      differing years. In total, 156 prostate tissues from transurethral resection of
      the prostate procedures for benign prostatic hyperplasia from 1983 to 2013 were
      collected. These were distributed to form seven categories: 1983-1984 (n = 20),
      1988-1989 (n = 25), 1993-1994 (n = 21), 1998-1999 (n = 21), 2003-2004 (n = 21),
      2008-2009 (n = 20) and 2012-2013 (n = 21). Ten-MUm-thick tissue sections were
      floated onto Low-E (IR-reflective) slides for ATR-FTIR or Raman spectroscopy. The
      prostate tissue spectral phenotype altered in a temporal fashion. Examination of
      the two categories that are at least one generation (30 years) apart indicated
      highly-significant segregation, especially in spectral regions containing DNA and
      RNA bands (~1,000-1,490 cm(-1)). This may point towards alterations that have
      occurred through genotoxicity or through epigenetic modifications.
      Immunohistochemical studies for global DNA methylation supported this. This study
      points to a trans-generational phenotypic change in human prostate. 

PMID- 26310633
TI  - Structural Changes and Proton Transfer in Cytochrome c Oxidase.
AB  - In cytochrome c oxidase electron transfer from cytochrome c to O2 is linked to
      transmembrane proton pumping, which contributes to maintaining a proton
      electrochemical gradient across the membrane. The mechanism by which cytochrome c
      oxidase couples the exergonic electron transfer to the endergonic proton
      translocation is not known, but it presumably involves local structural changes
      that control the alternating proton access to the two sides of the membrane. Such
      redox-induced structural changes have been observed in X-ray crystallographic
      studies at residues 423-425 (in the R. sphaeroides oxidase), located near heme a.
      The aim of the present study is to investigate the functional effects of these
      structural changes on reaction steps associated with proton pumping. Residue
      Ser425 was modified using site-directed mutagenesis and time-resolved
      spectroscopy was used to investigate coupled electron-proton transfer upon
      reaction of the oxidase with O2. The data indicate that the structural change at
      position 425 propagates to the D proton pathway, which suggests a link between
      redox changes at heme a and modulation of intramolecular proton-transfer rates. 

PMID- 26310634
TI  - Quantitative Neuropeptidome Analysis Reveals Neuropeptides Are Correlated with
      Social Behavior Regulation of the Honeybee Workers.
AB  - Neuropeptides play vital roles in orchestrating neural communication and
      physiological modulation in organisms, acting as neurotransmitters,
      neuromodulators, and neurohormones. The highly evolved social structure of
      honeybees is a good system for understanding how neuropeptides regulate social
      behaviors; however, much knowledge on neuropeptidomic variation in the age
      related division of labor remains unknown. An in-depth comparison of the brain
      neuropeptidomic dynamics over four time points of age-related polyethism was
      performed on two strains of honeybees, the Italian bee (Apis mellifera ligustica,
      ITb) and the high royal jelly producing bee (RJb, selected for increasing royal
      jelly production for almost four decades from the ITb in China). Among the 158
      identified nonredundant neuropeptides, 77 were previously unreported,
      significantly expanding the coverage of the honeybee neuropeptidome. The fact
      that 14 identical neuropeptide precursors changed their expression levels during
      the division of labor in both the ITb and RJb indicates they are highly related
      to task transition of honeybee workers. These observations further suggest the
      two lines of bees employ a similar neuropeptidome modification to tune their
      respective physiology of age polyethism via regulating excretory system,
      circadian clock system, and so forth. Noticeably, the enhanced level of
      neuropeptides implicated in regulating water homeostasis, brood pheromone
      recognition, foraging capacity, and pollen collection in RJb signify the fact
      that neuropeptides are also involved in the regulation of RJ secretion. These
      findings gain novel understanding of honeybee neuropeptidome correlated with
      social behavior regulation, which is potentially important in neurobiology for
      honeybees and other insects. 

PMID- 26310635
TI  - Performance management versus bullying and harassment: an educator perspective.

PMID- 26310637
TI  - [Break new grounds for the future and the process of innovating: celebrating the
      65th anniversary of Chinese Journal of Pediatrics].

PMID- 26310638
TI  - [For a grander sight to the next level: celebrating the 65th anniversary of
      Chinese Journal of Pediatrics].

PMID- 26310636
TI  - Proximal muscle weakness as a result of osteomalacia associated with celiac
      disease: a case report.
AB  - A 24-year-old woman suffering from back and hip pain with difficulty in walking
      was reported. She had proximal muscle weakness. Laboratory findings led to the
      diagnosis of osteomalacia. Positivity of antibodies strengthened suspicion of
      celiac disease. In patients with proximal muscle weakness, osteomalacia should be
      considered in differential diagnosis even in a young woman. INTRODUCTION: A 24
      year-old woman suffering from back pain, bilateral hip pain, and difficulty in
      walking was reported. Her symptoms had started in the first trimester of
      pregnancy. METHODS: In her physical examination, proximal muscle weakness and
      waddling gait pattern were determined. Her lumbar spine and hip MRI revealed no
      obvious pathological findings. Electromyography showed a myophatic pattern.
      RESULTS: Physical examination, normal values of creatine kinase, and muscle
      biopsy were supplied to exclude the diagnosis of primer muscle diseases.
      Laboratory findings led to the diagnosis of osteomalacia with normal renal
      function. Gastrointestinal symptoms and positivity of anti-gliadin and anti
      endomysium antibodies strengthened the suspicion of celiac disease as a cause of
      the osteomalacia. The diagnosis of celiac disease was confirmed with duodenal
      mucosal biopsy. CONCLUSION: In patients with proximal muscle weakness and
      waddling gait pattern, osteomalacia should be considered in differential
      diagnosis even in a young woman and underlying disease should be investigated.

PMID- 26310639
TI  - [Analysis of articles published in Chinese Journal of Pediatrics from 2005 to
      2014].
AB  - OBJECTIVE: To explore the status of articles published in Chinese Journal of
      Pediatrics from 2005 to 2014. METHOD: All the articles published in Chinese
      Journal of Pediatrics from 2005 to 2014 were searched at Wanfang Medical Online
      database. The total number and citations of articles, authors, agency, single
      article citation, internet downloads, columns, fund and Mesh were analyzed. The
      end of searching period was January 2015. RESULT: From 2005 to 2014, 2814
      articles were published in Chinese Journal of Pediatrics, 235 to 380 articles per
      year. A total of 1 596 articles were cited, the citation rate was 56.16%, total
      number of citation was 15 428. Among single article citations, of the top 20
      articles, 55% (11/20) were those published in the Standard/Protocol/Guide column.
      Of the top 20 papers most frequently downloaded on internet, 100% were articles
      published in the Standard/Protocol/Guide column. During the recent 10 years, the
      source of the papers published in the journal covered 31 provinces,
      municipalities and autonomous regions. The column that published the largest
      number of articles was Original Article (911, 32.05%), followed by Case Report
      (336,11.82%) and Review (245, 8.62%). Of the total number of articles published
      in the journal, 747 were supported by fund, which accounted for 26%. The articles
      supported by national fund accounted for 8%. CONCLUSION: Articles published in
      Chinese Journal of Pediatrics had high-quality and can reflect the development
      and research progress in pediatric medicine. It is one of the most important
      information resources in pediatric academic fields in China.

PMID- 26310640
TI  - [Standard for diagnosis and management of Helicobacter pylori infection in
      Chinese children].

PMID- 26310641
TI  - [Guidelines for Helicobacter pylori infection in children in China].

PMID- 26310642
TI  - [European Society for Pediatric Gastroenterology, Hepatology, and
      Nutrition/European Society for Pediatric Infectious Diseases evidence-based
      guidelines for the management of acute gastroenteritis in children in Europe:
      update 2014].

PMID- 26310643
TI  - [Tight junction protein expression of gastric mucosa and its significance in
      children with Helicobacter pylori infection].
AB  - OBJECTIVE: To understand the junction protein expression of gastric mucosa
      including occlusal proteins (occludin), closed protein-4 (claudin-4), zonula
      occluden-1(ZO-1), epithelial cadherin (E-cadherin), and beta ring protein (beta
      catenin) and the clinical significance in children with Helicobacter pylori (Hp)
      infection. METHOD: Seventy patients in whom gastric endoscopy was performed
      because of nausea, vomiting, abdominal pain, bloating, acid reflux, melena, and
      other gastrointestinal symptoms were enrolled in this study from Dec. 2010 to
      Apr. 2013 in our hospital. Informed consent was signed by their parents, and the
      study was in accordance with the principles of medical ethics. Hp positivity was
      confirmed if both respiratory urea test (RUT) and Hp were positive by gastric
      mucosal pathology. Gastric mucosal samples from 70 patients were enrolled in this
      study, 23 of them were Hp negative, 47 of them were Hp positive (24 cases without
      peptic ulcer, 23 cases with peptic ulcer). The mRNA levels and protein expression
      of tight junction protein of gastric mucosa were measured by RT-PCR and Western
      blot respectively. The location and semi quantitative content of E-cadherin and
      beta-catenin in gastric mucosa were detected by immunohistochemical staining
      method. RESULT: The mRNA level of E-cadherin, beta-catenin, ZO-1 in the Hp
      positive group regardless of peptic ulcer was significantly lower than that in
      the Hp negative group. Hp positive without peptic ulcer group were 0.0008,
      0.0040, 0.0014, respectively; Hp positive with peptic ulcer group were 0.0010,
      0.0090, 0.0013, respectively; Hp negative group were 0.0137, 0.0423, 0.0198,
      respectively (F values were 36.956, 39.893, 38.962, respectively, all P<0.05).
      The expression of claudin-4 mRNA in Hp positive group with peptic ulcer increased
      significantly, the difference among Hp positive group with peptic ulcer, Hp
      positive group without peptic ulcer and Hp negative group was statistically
      significant (0.1438 vs. 0.0926 vs. 0.0789) (F value was 11.964, P<0.05), while
      the difference of occludin mRNA levels among the three groups was not
      statistically significant.Immunohistochemistry results showed that the score of E
      cadherin, beta-catenin positive cell in the Hp positive patients were also
      significantly lower than that in the Hp negative group (t values were 3.981 and
      2.340, all P<0.05, respectively). Western blot results showed that the protein
      levels of beta-catenin in Hp positive group with peptic ulcer were significantly
      lower than that in Hp negative group, while the protein levels of E-cadherin in
      Hp positive patients regardless of peptic ulcer were decreased significantly in
      Hp negative group. CONCLUSION: Our results revealed that the tight junction
      protein E-cadherin, beta-catenin, ZO-1 expression of gastric mucosa were
      decreased in children with Hp infection, while claudin-4 expression was increased
      in Hp positive patients with peptic ulcer, suggesting that damage to gastric
      epithelial barrier function may be the main pathogenesis of Hp associated gastric
      diseases in children.

PMID- 26310644
TI  - [Vitamin D deficiency and risk factors in children with Crohn's disease].
AB  - OBJECTIVE: To observe the relationship between vitamin D status and seasons,
      disease activity, disease location, growth and steroid treatment in children with
      Crohn's disease (CD). To search for the risk factors of vitamin D deficiency in
      CD children. To discuss the role of vitamin D in the pathogenesis and treatments
      of CD. METHOD: Sixty CD children (63.3% male) and 121 sex- and age-matched
      healthy subjects were enrolled. Data including growth, clinical characteristics,
      time for vitamin D blood test, erythrocyte sedimentation rate, C reactive
      protein, serum 25(OH)D concentration and steroid treatments were collected. The
      relationship between vitamin D status and disease activity, disease location,
      growth and steroid treatments in children with CD were analized. RESULT: The
      serum concentration of 25(OH)D was 57.2(22.3-246.0) nmol/L, which was
      significantly lower than that of controls (67.3 (57.3-78.4) nmol/L) (Z=-5.009,
      P=0.000). Hypovitaminosis D was most prevalent during the winter and spring
      (November to April, 46.8(31.8-83.4) nmol/L) rather than summer and autumn (May to
      October, 63.3(22.3-246.0) nmol/L, Z=-1.994, P=0.046). Univariate logistic
      regression demonstrated that factors increasing the risk of vitamin D deficiency
      in Crohn's disease were: age over 10 years (OR=4.571, 95% CI: 1.452-14.389),
      small intestine involved diseases (OR=5.211, 95% CI: 1.278-21.237), high C
      reactive protein levels (>=8 mg/L) (OR=4.500, 95% CI: 1.094-18.503) and steroid
      therapy (OR=4.297, 95% CI: 1.413-13.068). Among those risk factors, all but age
      were determined to be risks of vitamin D deficiency by further multivariate
      logistic regression. There was no significant correlation between vitamin D
      deficiency and gender, disease duration, stricture, penetration, perianal disease
      (fistula, ulcer or abscess), white blood cell counts, hemoglobin, platelet
      counts, erythrocyte sedimentation rate, serum albumin levels, pediatric Crohn's
      disease activity index and nutrition therapy (P>0.05). CONCLUSION:
      Hypovitaminosis D was prevalent in children with CD. Serum concentration of
      vitamin D was associated with season. Steroid treatment, small intestine involved
      disease and high C reactive protein (more than 8 mg/L) are risk factors of
      vitamin D deficiency in CD children.

PMID- 26310645
TI  - [Virulence genes and clinical features of Clostridium difficile-associated
      diarrhea in children].
AB  - OBJECTIVE: Clostridium difficile is an obligate anaerobic Gram-positive bacillus,
      it can cause Clostridium difficile-associated diarrhea (CDAD). This study aimed
      to investigate the virulence genes and clinical features of CDAD in children by
      gene detection. METHOD: From May 2012 to January 2013, the 121 inpatients in
      Beijing Children's Hospital who suffered from diarrhea after antibiotics
      treatment were detected for Clostridium difficile virulence genes including the
      five genes for pathogenic loci (tcdA, tcdB, tcdC, tcdD, tcdE) and the genes for
      binary toxin CDT (cdtA and cdtB) using polymerase chain reaction (PCR) in order
      to research the clinical features of CDAD, and analyze target products by
      sequencing. RESULTS: In the 121 children with diarrhea, 60 (49.6%) were toxin B
      positive,including 12 toxin A-positive and toxin B-positive (A+B+), 48 toxin A
      negative but toxin B-positive (A-B+). The toxin A-positive but toxin B-negative
      (A+B-) specimens or binary toxin (cdtA and cdtB)-positive specimens were not
      detected. Of 60 tcdB-positive specimens, tcdC, tcdD and tcdE positive specimens
      were 24 (40%), 25 (42%), 24 (40%), respectively. The sequencing results of tcdA,
      tcdB, tcdC, tcdD, and tcdE gene were consistent with the reference sequence. In
      the 60 children with CDAD, infants (<=3 years) accounted for 62% (37/60). The
      duration of diarrhea was 3-77 days, and 42 (70%) cases had acute diarrhea; 39
      (65%) patients had fever, 40 (67%) had anemia, 36 (60%) had abnormal white blood
      cell count, 30 (50%) had hypoalbuminemia, 25 (42%) had elevated C-reactive
      protein (CRP). The level of CRP in positive group was significantly higher
      compared to the negative group (45.0(16.0,89.0) mg/L vs. 19.0(14.5,41.5) mg/L, Z=
      2.008, P=0.045). The level of plasma albumin in positive group was significantly
      lower compared to the negative group (35.3(29.7,39.8) g/L vs. 38.5(33.9,41.5)
      g/L, Z=-2.610, P=0.009). There were no significant differences in gender, age,
      duration of diarrhea, hospital staytime, time of using antibiotics and laboratory
      test between A+B+ group and A-B+ group (all P>0.05). CONCLUSION: The main
      virulence genotype of Clostridium difficile was toxin A-negative but toxin B
      positive in this research. The clinical features of CDAD in children were acute
      diarrhea with fever. Laboratory examination showed that white blood cell count
      was abnormal, CRP was increased, hemoglobin and plasma albumin were reduced.

PMID- 26310646
TI  - [Suggestions on the diagnostic criteria of childhood obstructive sleep apnea
      hypopnea syndrome].
AB  - OBJECTIVE: To evaluate the sleep architecture and hypoxia and clinical features
      of habitual snoring children with an obstructive sleep apnea-hypopnea index
      (OAHI) 1 to 5. METHOD: The polysomnographic data of 267 children aged from 2 to
      16 years with habitual snoring were analyzed retrospectively, and the clinical
      features were analyzed in 108 of the children. The recruited children were
      divided into primary snoring group (PS group, OAHI<=1), obstructive sleep apnea
      hypopnea syndrome (OSAHS) group (1<OAHI<=5 and obstructive apnea index<=1),
      lowest oxygen saturation (LSpO2<=0.92) and OSAHS group (OAHI>5 or dostructive
      apnea index>1, LSpO2<0.92). RESULT: The oxygen desaturation index of the
      intermediate OSAHS group (3.8+/-0.4) was significantly higher than that of PS
      group (1.6+/-0.1) (chi2=34.5, P<0.01). The LSpO2 of intermediate OSAHS group was
      significantly lower than that of PS group (89(87,91) vs. 93(91,94), chi2=40.2,
      P<0.01). Comparing to the PS group, the non-rapid eye movement 1 ratio (N1%) was
      significantly higher (19.0+/-1.2 vs. 14.2+/-0.1, chi2=14.1, P<0.01), and the non
      rapid eye movement 3 ratio (N3%) was significantly lower (24.4+/-1.0 vs. 29.0+/
      1.1, P<0.01) in the intermediate OSAHS group. The pediatric questionnaire score
      intermediate OSAHS group was higher than PS (0.41+/-0.19 vs. 0.28+/-0.14,
      chi2=8.52, P=0.01). The adenoids-nasopharynx ratio was higher than that of PS
      group (0.70+/-0.07 vs. 0.62+/-0.10, chi2=8.96, P=0.01). The hypertrophy of tonsil
      was higher than PS group (2(1,2) vs. 1(1,2), chi2=7.95, P<0.05). CONCLUSION:
      Hypoxia and abnormal sleep structure are present in HS children with an OAHI of 1
      to 5, and they also have the clinical features of OSAHS.

PMID- 26310647
TI  - [Allergic bronchopulmonary aspergillosis: a report of four cases with literature
      review].
AB  - OBJECTIVE: To understand the clinical characteristics of allergic
      bronchopulmonary aspergillosis (ABPA) so as to diagnose and treat the disease
      earlier. METHOD: A retrospective study was conducted on ABPA patients diagnosed
      in the Second Department of Respiratory Medicine, Beijing Children's Hospital
      Affiliated to Capital Medical University from April 2010 to March 2014. The
      literature of children's ABPA retrieved from the databases at home and abroad in
      recent 10 years were analyzed. RESULT: (1) Among the 4 cases of ABPA, cystic
      fibrosis (CF) and asthma were diagnosed in 2 and 1 cases, respectively. Cough was
      present in 3 patients, recurrent wheezing in 2 and chest tightness in 1 case. CT
      scans showed central bronchiectasis in all 4 cases, while 1 patient had migratory
      shadows. All cases had elevated serum total IgE, immediate cutaneous reaction to
      aspergillus fumigatus; A. fumigatus-specific IgE and IgG were positive in 4
      cases. The diagnosis of the 4 cases was confirmed according to the history,
      radiologic investigations and laboratory findings. All of them were improved
      after the treatment with glucocorticosteroid and antifungal agents (voriconazole
      or itraconazole). (2) We retrieved articles on the ABPA in the databases at home
      and abroad published in the recent 10 years, there were 22 foreign reports and
      only one case in domestic report. Among the 22 foreign cases, 16 patients were
      CF, 3 were asthmatics. ABPA was diagnosed as the initial presentation in only one
      case with CF. CONCLUSION: In asthmatics or the patients with allergic disease, if
      there are highly elevated serum total IgE, central bronchiectasis or recurrent
      atelectasis in chest imaging, the patients should be further investigated for
      ABPA. The diagnosed cases of ABPA should be screened for CF routinely.

PMID- 26310648
TI  - [Epidemiologic characteristics and the relationship with disease severity of
      respiratory syncytial virus genotypes from children with lower respiratory tract
      infection in the southern Zhejiang province].
AB  - OBJECTIVE: To investigate the epidemiological characteristics of respiratory
      syncytial virus (RSV) subtypes and genotypes in southern Zhejiang province, and
      to determine whether RSV genotypes are correlated with the disease severity of
      lower respiratory tract infection (LRTI). METHOD: Nasopharyngeal secretions (NPS)
      from children under 5 years of age who were hospitalized with LRTI during 5
      consecutive seasons from July 1, 2009 to June 30, 2014 were collected. RSV
      antigen was determined using direct immunofluorescence (DIF). Two hundred strains
      of RSV were randomly selected from each epidemic season. RNA was extracted and
      identified as subtype A or B by using reverse transcription-polymerase chain
      reaction (RT-PCR), and randomly selected strains of the full length attachment
      (G) genes of both subtype A and subtype B were amplified by PCR and sequencing.
      Clinical data were collected, and the disease severity between different
      genotypes were compared simultaneously. RESULT: Of the total 1 000 randomly
      selected RSV positive samples, 462 (46.2%) and 538 (53.8%) samples were
      identified as subtype A and B, respectively. It was found that subtype B
      predominated in the 2009-2010 and 2012-2014 epidemic seasons and subtype A in
      2010-2012 epidemic seasons. A total of 112 strains of complete sequences of G
      genes were obtained, including four subtype A genotypes NA1, NA4, GA2 and ON1,
      and six subtype B genotypes BA8-10, BA-C, CB1, and GB2. Phylogenetic analysis
      revealed that 39/52 (75.0%) subtype A strains were classified as NA1 genotype,
      followed by ON1 genotype (10/52,19.2%) and 44/60 (73.3%) subtype B strains were
      classified as BA9 genotype, followed by BA8 genotype (6/60,10.0%). BA9 was the
      predominant genotype among subtype B except 2010-2011 epidemic season, while NA1
      was the predominant genotype among subtype A except 2013-2014 epidemic season.
      Only ON1 and BA9 genotypes were checked out during 2013-2014 epidemic season.
      There was statistically significant difference in the average severity score of
      illness in 39 cases infected with NA1 genotype (4.154) and 44 cases of BA9
      genotype (3.341) (U=642.500, P<0.05). Furthermore, in the rate of oxygen uptake,
      the percentage of those infected with NA1 genotype (33.3%) was higher than those
      infected with BA9 genotype (13.6%) (chi2=4.544, P<0.05). However, there were no
      significant difference in the age, clinical symptoms, the percentage of intensive
      care unit admission, length of hospitalization and the outcome of the disease
      between NA1 and BA9 infection. CONCLUSION: The shift of predominant RSV subtype
      from 2009 to 2014 were B-A-A-B-B in the southern areas of Zhejiang province.
      Multiple genotypes co-circulated during five RSV epidemic seasons. NA1 and BA9
      genotypes were the predominant genotypes of subtype A and B, respectively.
      Compared with infection with BA9 genotype, NA1 genotype infection was associated
      with more severe disease and proportion of patients needed oxygen therapy was
      higher.

PMID- 26310649
TI  - [A patient with eosinophilic gastroenteritis presenting with acute pancreatitis].

PMID- 26310650
TI  - [Interpretations of consensus guidelines of ECCO/ESPGHAN on the medical
      management of pediatric Crohn's disease].

PMID- 26310651
TI  - [Update for the diagnosis and resistant associated gene of Clostridium
      difficile].

PMID- 26310652
TI  - [Application of dried blood spot method in screening Gaucher's disease].

PMID- 26310653
TI  - [Propranolol as a possible new pharmacologic treatment of retinopathy of
      prematurity].

PMID- 26310655
TI  - Curcumin induces the apoptosis of A549 cells via oxidative stress and MAPK
      signaling pathways.
AB  - Curcumin has been found to exhibit anticancer activity and certain studies have
      shown that curcumin triggers the apoptosis of human A549 lung adenocarcinoma
      cells. However, the mechanism underlying curcumin-mediated apoptosis is not
      completely understood. The present study was designed to investigate the effect
      of curcumin on the induction of apoptosis and apoptosis-related factors in human
      A549 lung adenocarcinoma cells. Treatment of A549 cells with curcumin caused a
      concentration-dependent inhibition of cell growth and an increase in apoptosis,
      as confirmed by THE MTT assay, flow cytometry and morphology analysis. Curcumin
      treatment of A549 cells induced a loss of the mitochondrial membrane potential
      and increased cytosolic cytochrome c. Furthermore, curcumin-induced apoptosis was
      accompanied by changes in intracellular oxidative stress-related enzymes,
      including decreased intracellular reactive oxygen species levels, increased
      superoxide dismutase and decreased malondialdehyde and 4-hydroxynonenal. In
      addition, induction of apoptosis was also accompanied by phosphorylation and
      activation of mitogen-activated protein kinase signaling pathway factors c-Jun N
      terminal kinase, p38 and extracellular signal-regulated kinase. 

PMID- 26310656
TI  - First description of B chromosomes in the Hyphessobrycon (Characiformes,
      Characidae) genus: a hypothesis for the extra element of Hyphessobryconeques
      Steindachner, 1882.
AB  - The Hyphessobrycon are allocated in the incertae sedis group of the Characidae
      family, one of the genera with more species of the group. The chromosomes of some
      species of Hyphessobrycon are known, and the diploid number most common for genus
      is 2n = 50 chromosomes. The aims of this study were to examine the karyotype
      macrostructure in the Hyphessobryconeques Steindachner, 1882, and show a new
      origin hypothesis for B chromosomes. The diploid number observed for
      Hyphessobryconeques was 2n = 52 chromosomes, and a karyotype formulae of 12m +
      18sm + 8st + 14a, with FN (fundamental number) = 90 for both sexes. Only two
      females showed one B chromosome. The heterochromatin was observed mainly on
      centromeric regions, and in the long arm of the B chromosome. In this paper, the
      relationship of the B chromosome of Hyphessobryconeques with an occasional
      chromosome rearrangement was discussed. 

PMID- 26310657
TI  - Mycobacterium tuberculosis beta-gentiobiosyl diacylglycerides signal through the
      pattern recognition receptor Mincle: total synthesis and structure activity
      relationships.
AB  - Mycobacterium tuberculosis H37Ra produces a range of immunogenic beta
      gentiobiosyl diacylglycerides. We report the total synthesis of several candidate
      structures and show that these compounds signal weakly through mouse, but not
      human, Mincle. Structure-activity relationships reveal a striking dependence upon
      acyl chain length for gentiobiosyl diacylglyceride signalling through Mincle.
      Significantly, a truncated beta-glucosyl diglyceride was shown to provide potent
      signalling through both human and mouse Mincle and could activate murine bone
      marrow derived dendritic cells. 

PMID- 26310661
TI  - Controlling intermolecular aurophilicity in emissive dinuclear Au(I) materials
      and their luminescent response to ammonia vapour.
AB  - The concept that hydrogen bonding cations can reduce the coulombic repulsion
      inherent to anionic gold species and thereby trigger aurophilicity is realized
      with three new photoluminescent compounds of the form [Q]2[Au2(i-mnt)2] (i-mnt =
      (CN)2C[double bond, length as m-dash]CS2(2-), Q = 3,5-dimethylpyrazolium,
      piperidinium). These compounds illustrate unprecedented supramolecular
      aurophilicity between the anions, the emission of which is significantly red
      shifted compared to zero-dimensional analogues, a direct result of the aurophilic
      network. The piperidinium salt exhibits a vapochromic/luminescent response to
      ammonia, inducing a change in colour of the reflectance and emission from red to
      yellow. These results demonstrate the ability to rationally control the formation
      of supramolecular metallophilic networks via the incorporation of hydrogen
      bonding cations. 

PMID- 26310658
TI  - Applying proprioceptive neuromuscular facilitation stretching: optimal
      contraction intensity to attain the maximum increase in range of motion in young
      males.
AB  - [Purpose] Proprioceptive neuromuscular facilitation (PNF) stretching is known to
      be effective in increasing joint ROM. The PNF stretching technique first induces
      an isometric contraction in the muscles to be stretched, but no agreement
      concerning the optimal contraction intensity has yet been reached. The purpose of
      the present study was to examine the effect of contraction intensity on ROM while
      applying PNF stretching. [Subjects and Methods] Sixty male subjects were randomly
      assigned to one of four groups (three experimental groups and one control group).
      Each experimental group applied one of three contraction intensities (100%, 60%,
      and 20%) defined by the MVIC ratio, and the control group did not receive any
      intervention during the experiment. PNF stretching was applied to left knee
      extensors to compare changes in the knee joint flexion angle. [Results] The
      results showed that the changes in ROM were larger for the 60% and 100% groups
      compared with the 20% group. The changes in ROM were lowest in the control group.
      [Conclusion] The present results indicate that while applying the PNF stretching,
      it is not necessary to apply the maximum intensity of muscle contraction.
      Moderate isometric contraction intensities may be optimal for healthy young
      males, while a sufficient effect can be obtained even with a low contraction
      intensity. 

PMID- 26310662
TI  - Ambulatory Blood Pressure Variability Increases Over a 10-Year Follow-Up in
      Community-Dwelling Older People.
AB  - BACKGROUND: Greater ambulatory blood pressure variability (ABPV) is associated
      with end-organ damage and increased mortality. Age-related changes in the
      cardiovascular and autonomic nervous systems make age-associated increases in
      ABPV likely. Cross-sectional studies support this hypothesis, showing greater
      ABPV among older compared to younger adults. The only longitudinal study to
      examine changes in ABPV, however, found ABPV decreased over 5 years follow-up.
      This unexpected observation probably reflected the highly selected nature of the
      study participants. METHODS: In this longitudinal study, we assessed changes in
      ABPV over 10 years in a community-cohort of older people. In addition, we
      examined the extent to which ABPV was predicted by demographics, cardiovascular
      risk factors, and medication. Clinical examination and 24-hour ambulatory blood
      pressure monitoring were carried out at baseline and at 10 years follow-up in 83
      people, median age 70 years. ABPV was calculated using SD and coefficient of
      variation (Cv). Three time periods were examined: daytime, nighttime, and 24
      hours. RESULTS: Daytime and 24-hour, systolic and diastolic, SD, and Cv were
      significantly greater at follow-up than at baseline (P < 0.001 in all cases).
      Mean BP did not change. CONCLUSIONS: Multilevel modeling showed follow-up
      interval had a significant, positive effect on SD and Cv (P < 0.004), independent
      of age, sex, and medication.ABPV increased over a 10-year follow-up despite
      stable mean BP. ABPV may therefore be an additional target for treatment in older
      people. Future studies should examine what degree of ABPV is harmful and if
      control of ABPV reduces adverse outcome.

PMID- 26310663
TI  - The Association of Pediatric Obesity With Nocturnal Non-Dipping on 24-Hour
      Ambulatory Blood Pressure Monitoring.
AB  - BACKGROUND: Obesity has been linked with abnormal nocturnal dipping of blood
      pressure (BP) in adults, which in turn is associated with poor cardiovascular
      outcomes. There are few data regarding abnormal dipping status in the obese
      pediatric population. The goal of this study was to further describe the
      relationship between obesity and non-dipping status on ambulatory blood pressure
      monitor (ABPM) in children. METHODS: We conducted a cross-sectional study using a
      database of patients aged 5-21 years who had undergone 24-hour ABPM at Seattle
      Children's Hospital from January 2008 through May 2014. Subjects were grouped by
      body mass index (BMI) into lean (BMI 15th-85th percentile) and obese (BMI >95th
      percentile) groups. RESULTS: Compared to lean subjects (n = 161), obese subjects
      (n = 247) had a prevalence ratio (PR) for non-dipping of 2.15, adjusted for race
      (95% confidence interval (CI) = 1.25-3.42). Increasing severity of obesity was
      not further associated with nocturnal non-dipping. Nocturnal non-dipping was not
      associated with left ventricular hypertrophy (PR = 1.01, 95% CI = 0.71-1.44).
      CONCLUSIONS: These results suggest that in children, just as in adults, obesity
      is related to a relatively decreased dipping in nocturnal BP.

PMID- 26310665
TI  - Breast bruises and breast cancer.

PMID- 26310664
TI  - Multiple physical and mental health comorbidity in adults with intellectual
      disabilities: population-based cross-sectional analysis.
AB  - BACKGROUND: Adults with intellectual disabilities have increased early mortality
      compared with the general population. However, their extent of multimorbidity
      (two or more additional conditions) compared with the general population is
      unknown, particularly with regards to physical ill-health, as are associations
      between comorbidities, neighbourhood deprivation, and age. METHODS: We analysed
      primary health-care data on 1,424,378 adults registered with 314 representative
      Scottish practices. Data on intellectual disabilities, 32 physical, and six
      mental health conditions were extracted. We generated standardised prevalence
      rates by age-groups, gender, and neighbourhood deprivation, then calculated odds
      ratio (OR) and 95 % confidence intervals (95 % CI) for adults with intellectual
      disabilities compared to those without, for the prevalence, and number of
      condition. RESULTS: Eight thousand fourteen (0.56 %) had intellectual
      disabilities, of whom only 31.8 % had no other conditions compared to 51.6 %
      without intellectual disabilities (OR 0.26, 95 % 0.25-0.27). The intellectual
      disabilities group were significantly more likely to have more conditions, with
      the biggest difference found for three conditions (10.9 % versus 6.8 %; OR 2.28,
      95 % CI 2.10-2.46). Fourteen physical conditions were significantly more
      prevalent, and four cardiovascular conditions occurred less frequently, as did
      any cancers, and chronic obstructive pulmonary diseases. Five of the six mental
      health conditions were significantly more prevalent. For the adults with
      intellectual disabilities, no gradient was seen in extent of multimorbidity with
      increasing neighbourhood deprivation; indeed findings were similar in the most
      affluent and most deprived areas. Co-morbidity increased with age but is highly
      prevalent at all ages, being similar at age 20-25 to 50-54 year olds in the
      general population. CONCLUSIONS: Multi-morbidity burden is greater, occurs at
      much earlier age, and the profile of health conditions differs, for adults with
      intellectual disabilities compared with the general population. There is no
      association with neighbourhood deprivation; people with intellectual disabilities
      need focussed services irrespective of where they live, and at a much earlier age
      than the general population. They require specific initiatives to reduce
      inequalities.

PMID- 26310666
TI  - Enhanced secretion of a methyl parathion hydrolase in Pichia pastoris using a
      combinational strategy.
AB  - BACKGROUND: Although Pichia pastoris has been successfully used to produce
      various recombinant heterologous proteins, the efficiency varies. In this study,
      we used methyl parathion hydrolase (MPH) from Ochrobactrum sp. M231 as an example
      to study the effect of protein amino acid sequence on secretion from P. pastoris.
      RESULTS: The results indicated that the protein N-terminal sequence, the
      endoplasmic reticulum (ER) retention signal (KKXX) at the protein C-terminus, and
      the acidic stability of the protein could affect its secretion from P. pastoris.
      Mutations designed based on these sequence features markedly improved secretion
      from P. pastoris. In addition, we found that the secretion properties of a
      protein can be cumulative when all of the above strategies are combined. The
      final mutant (CHBD-DQR) designed by combining all of the strategies greatly
      improved secretion and the secreted MPH activity of CHBD-DQR was enhanced up to
      195-fold compared with wild-type MPH without loss of catalytic efficiency.
      CONCLUSIONS: These results demonstrate that the secretion of heterologous
      proteins from P. pastoris could be improved by combining changes in multiple
      protein sequence features.

PMID- 26310668
TI  - Growth-inhibitory and chemosensitizing effects of microRNA-31 in human
      glioblastoma multiforme cells.
AB  - The constitutive activation of signal transducer and activator of transcription 3
      (STAT3) contributes to resistance to temozolomide (TMZ) in glioblastoma
      multiforme (GBM). The aim of this study was to explore the biological role of
      microRNA-31 (miR-31) in GBM, particularly its role in the regulation of TMZ
      chemosensitivity. For this purpose, the human GBM cell lines, U251 and U87, were
      transfected with a miR-31 precursor (pre-miR-31), and cell proliferation,
      apoptosis and STAT3 phosphorylation were then assessed. To evaluate the effects
      of miR-31 on TMZ cytotoxicity, the cells were transfected with pre-miR-31 and
      exposed to 100 uM TMZ for 72 h prior to cell proliferation and apoptosis
      analysis. A constitutively active STAT3 mutant was co-transfected with pre-miR-31
      into the cells to confirm the mediating role of STAT3 signaling. The enforced
      expression of miR-31 significantly reduced cell proliferation and induced
      mitochondrial apoptosis, as manifested by the loss of mitochondrial membrane
      potential and the increase in caspase-9 and caspase-3 activity. The
      phosphorylation level of STAT3 was significantly decreased by the overexpression
      of miR-31. The co-delivery of the constitutively active STAT3 mutant blocked the
      tumor suppressive effects of miR-31. In addition, miR-31 overexpression
      significantly enhanced the cytotoxic effects of TMZ on the GBM cells, as
      evidenced by the accelerated suppression of cell proliferation and the induction
      of apoptosis. The chemosensitizing effects of miR-31 were significantly impaired
      by the expression of the constitutively active STAT3 mutant. Taken together, our
      results indicate that miR-31 triggers mitochondrial apoptosis and potentiates TMZ
      cytotoxicity in GBM cells largely through the suppression of STAT3 activation.
      Thus, the restoration of miR-31 expression may be of therapeutic beenefit in the
      treatment of GBM. 

PMID- 26310667
TI  - Left ventricular mechanical dysfunction in diet-induced obese mice is exacerbated
      during inotropic stress: a cine DENSE cardiovascular magnetic resonance study.
AB  - BACKGROUND: Obesity is a risk factor for cardiovascular disease. There is
      evidence of impaired left ventricular (LV) function associated with obesity,
      which may relate to cardiovascular mortality, but some studies have reported no
      dysfunction. Ventricular function data are generally acquired under resting
      conditions, which could mask subtle differences and potentially contribute to
      these contradictory findings. Furthermore, abnormal ventricular mechanics
      (strains, strain rates, and torsion) may manifest prior to global changes in
      cardiac function (i.e., ejection fraction) and may therefore represent more
      sensitive markers of cardiovascular disease. This study evaluated LV mechanics
      under both resting and stress conditions with the hypothesis that the LV
      mechanical dysfunction associated with obesity is exacerbated with stress and
      manifested at earlier stages of disease compared to baseline. METHODS: C57BL/6J
      mice were randomized to a high-fat or control diet (60 %, 10 % kcal from fat,
      respectively) for varying time intervals (n = 7 - 10 subjects per group per time
      point, 100 total; 4 - 55 weeks on diet). LV mechanics were quantified under
      baseline (resting) and/or stress conditions (40 MUg/kg/min continuous infusion of
      dobutamine) using cine displacement encoding with stimulated echoes (DENSE) with
      7.4 ms temporal resolution on a 7 T Bruker ClinScan. Peak strain, systolic strain
      rates, and torsion were quantified. A linear mixed model was used with Benjamini
      Hochberg adjustments for multiple comparisons. RESULTS: Reductions in LV peak
      longitudinal strain at baseline were first observed in the obese group after 42
      weeks, with no differences in systolic strain rates or torsion. Conversely,
      reductions in longitudinal strain and circumferential and radial strain rates
      were seen under inotropic stress conditions after only 22 weeks on diet.
      Furthermore, stress cardiovascular magnetic resonance (CMR) evaluation revealed
      supranormal values of LV radial strain and torsion in the obese group early on
      diet, followed by later deficits. CONCLUSIONS: Differences in left ventricular
      mechanics in obese mice are exacerbated under stress conditions. Stress CMR
      demonstrated a broader array of mechanical dysfunction and revealed these
      differences at earlier time points. Thus, it may be important to evaluate cardiac
      function in the setting of obesity under stress conditions to fully elucidate the
      presence of ventricular dysfunction.

PMID- 26310669
TI  - Release of insulin from PLGA-alginate dressing stimulates regenerative healing of
      burn wounds in rats.
AB  - Burn wound healing involves a complex set of overlapping processes in an
      environment conducive to ischaemia, inflammation and infection costing $7.5
      billion/year in the U.S.A. alone, in addition to the morbidity and mortality that
      occur when the burns are extensive. We previously showed that insulin, when
      topically applied to skin excision wounds, accelerates re-epithelialization and
      stimulates angiogenesis. More recently, we developed an alginate sponge dressing
      (ASD) containing insulin encapsulated in PLGA [poly(D,L-lactic-co-glycolic acid)]
      microparticles that provides a sustained release of bioactive insulin for >20
      days in a moist and protective environment. We hypothesized that insulin
      containing ASD accelerates burn healing and stimulates a more regenerative, less
      scarring healing. Using heat-induced burn injury in rats, we show that burns
      treated with dressings containing 0.04 mg insulin/cm(2) every 3 days for 9 days
      have faster closure, a higher rate of disintegration of dead tissue and decreased
      oxidative stress. In addition, in insulin-treated wounds, the pattern of
      neutrophil inflammatory response suggests faster clearing of the burned dead
      tissue. We also observe faster resolution of the pro-inflammatory macrophages. We
      also found that insulin stimulates collagen deposition and maturation with the
      fibres organized more like a basket weave (normal skin) than aligned and cross
      linked (scar tissue). In summary, application of ASD-containing insulin-loaded
      PLGA particles on burns every 3 days stimulates faster and more regenerative
      healing. These results suggest insulin as a potential therapeutic agent in burn
      healing and, because of its long history of safe use in humans, insulin could
      become one of the treatments of choice when repair and regeneration are critical
      for proper tissue function.

PMID- 26310670
TI  - Randomized Trial to Evaluate Tandospirone in Geographic Atrophy Secondary to Age
      Related Macular Degeneration: The GATE Study.
AB  - PURPOSE: To determine the safety and efficacy of AL-8309B (tandospirone) in the
      management of patients with geographic atrophy (GA) secondary to age-related
      macular degeneration (AMD) and obtain standardized data on GA lesion growth
      progression. DESIGN: Prospective, controlled, double-masked, randomized,
      multicenter phase 3 clinical trial. METHODS: setting: Forty-eight clinical sites.
      PATIENTS: Patients with GA associated with AMD were enrolled. All patients were
      followed for a minimum of 30 months, and up to 36 months. intervention
      procedures: Patients were randomized (1:1:1) to receive AL-8309B ophthalmic
      solution 1.0%, 1.75%, or vehicle, administered as a twice-daily topical ocular
      drop. MAIN OUTCOME MEASURES: The primary efficacy endpoint was mean annualized
      lesion enlargement from baseline as assessed with fundus autofluorescence (FAF)
      imaging. RESULTS: A total of 768 eyes of 768 patients were enrolled and treated
      with AL-8309B 1.0% (n = 250), AL-8309B 1.75% (n = 258), or vehicle (n = 260). An
      increase in mean lesion size was observed in both the AL-8309B and vehicle
      treatment groups, and growth rates were similar in all treatment groups.
      Annualized lesion growth rates were 1.73, 1.76, and 1.71 mm(2) for AL-8309B 1.0%,
      AL-8309B 1.75%, and vehicle, respectively. CONCLUSIONS: AL-8309B 1.0% and 1.75%
      did not affect lesion growth in eyes with GA secondary to AMD. There were no
      clinically relevant safety issues identified for AL-8309B. The large natural
      history dataset from this study is a valuable repository for future comparisons.

PMID- 26310671
TI  - Graphene/sulfur hybrid nanosheets from a space-confined "sauna" reaction for high
      performance lithium-sulfur batteries.
AB  - A space-confined "sauna" reaction system is introduced for the simultaneous
      reduction and functionalization of graphene oxide to unique graphene-sulfur
      hybrid nanosheets, in which thin layers of amorphous sulfur are tightly anchored
      on the graphene sheet via strong chemical bonding. Upon being used as the cathode
      material in lithium-sulfur batteries, the as-synthesized composite shows an
      excellent electrochemical performance. 

PMID- 26310672
TI  - Acidification triggers Andes hantavirus membrane fusion and rearrangement of Gc
      into a stable post-fusion homotrimer.
AB  - The hantavirus membrane fusion process is mediated by the Gc envelope
      glycoprotein from within endosomes. However, little is known about the specific
      mechanism that triggers Gc fusion activation, and its pre- and post-fusion
      conformations. We established cell-free in vitro systems to characterize
      hantavirus fusion activation. Low pH was sufficient to trigger the interaction of
      virus-like particles with liposomes. This interaction was dependent on a pre
      fusion glycoprotein arrangement. Further, low pH induced Gc multimerization
      changes leading to non-reversible Gc homotrimers. These trimers were resistant to
      detergent, heat and protease digestion, suggesting characteristics of a stable
      post-fusion structure. No acid-dependent oligomerization rearrangement was
      detected for the trypsin-sensitive Gn envelope glycoprotein. Finally,
      acidification induced fusion of glycoprotein-expressing effector cells with non
      susceptible CHO cells. Together, the data provide novel information on the Gc
      fusion trigger and its non-reversible activation involving lipid interaction,
      multimerization changes and membrane fusion which ultimately allow hantavirus
      entry into cells. 

PMID- 26310673
TI  - Partner HIV serostatus disclosure and determinants of serodiscordance among
      prevention of mother to child transmission clients in Nigeria.
AB  - BACKGROUND: Serodiscordance exists when the known HIV result of one member of a
      couple pair is positive while that of his/her partner is negative. In sub-Saharan
      Africa, in stable long-term couple partnerships (married or cohabiting),
      serodiscordance is a growing source of HIV-transmissions. This study aimed to
      ascertain across Nigeria, serodiscordance prevalence, partner HIV status
      disclosure and explore associations between suspected determinants and
      serodiscordance among PMTCT enrolled HIV positive pregnant women and their
      partners. METHODS: A retrospective Quality of Care performance evaluation was
      conducted in July 2013 among 544 HIV positive pregnant enrolees of PMTCT services
      in 62 comprehensive facilities across 5 of Nigeria's 6 geo-political zones. Data
      of client-partner pairs were abstracted from pre-existing medical records and
      analysed using chi-square statistics and logistic regression. RESULTS: A total of
      544 (22%) of 2499 clients with complete partner details were analysed. Clients'
      age ranged from 15 to 50 years with a mean of 30 years. Serodiscordant prevalence
      was 52% and chi-square test suggests no significant difference between
      serodiscordant and seroconcordant clients and their partners (p = 0.265).
      Serodiscordant rates were closely associated trend wise with national HIV sero
      prevalence rates and the median CD4+ count was 425 ul/mm(3) (IQR: 290-606
      ul/mm(3)). Similar proportion of clients (99%) received testing and agreed to
      disclose status to their partners. Yet, there was no association between clients
      agreement to disclose HIV status to their partners and these partners getting
      tested and receiving results (p = 0.919). Significantly, 87% of clients in
      concordant HIV positive relationships appeared to be symptomatic (WHO clinical
      stage 3 or 4) compared to 13% clients in HIV-discordant relationships (p <
      0.003). Client's age and CD4+ count did not aptly predict serodiscordance (Wald =
      0.011 and 0.436 respectively). However, the WHO clinical staging appeared to be a
      better predictor of serodiscordance and concordance than other variables (Wald =
      3.167). CONCLUSIONS: The results suggest that clinical staging (WHO) could be a
      better predictor of client- partner pair discordant or concordant HIV serostatus.
      Early partner testing and notification can avert seroconversion, hence properly
      designed and mainstreamed interventions that target serodiscordant couples are
      essential.

PMID- 26310674
TI  - Morphological distribution of testis cancer from Cancer Incidence in Five
      Continents Vol. X.

PMID- 26310675
TI  - From radial head to radiocapitellar to total elbow replacement: A case report.
AB  - INTRODUCTION: Radiocapitellar arthroplasty represents a possible treatment option
      for isolated osteoarthritis of the radial column. We report the first case of
      early failure of this procedure. PRESENTATION OF CASE: We present the case of a
      41-year old male who sustained a terrible triad injury to his right elbow and
      subsequently underwent radial head arthroplasty. Due to overstuffing of the
      radial head prosthesis, capitellar erosion occurred and radiocapitellar
      arthroplasty was thus performed. Only one year later, conversion of the
      radiocapitellar replacement to total elbow arthroplasty was required as a result
      of progressive ulnohumeral osteoarthritis. DISCUSSION: According to the currently
      limited clinical data, radiocapitellar arthroplasty provides satisfactory
      results. However, biomechanical analysis shows that available prostheses do not
      sufficiently reproduce the radiocapitellar anatomy. The design of the prosthesis
      might thus have contributed to the rapid progression of ulnohumeral erosion
      following radiocapitellar arthroplasty although the poor outcome may also be
      attributed to the trauma itself along with the inadequate initial treatment.
      CONCLUSIONS: The indication for radiocapitellar arthroplasty warrants careful
      consideration given the results of biomechanical analysis and the early failure
      due to progressive ulnohumeral erosion seen in the present case.

PMID- 26310676
TI  - Intrinsic and extrinsic determinants of central nervous system axon outgrowth
      into alginate-based anisotropic hydrogels.
AB  - Appropriate target reinnervation and functional recovery after spinal cord injury
      depend on longitudinally directed regrowth of injured axons. Anisotropic alginate
      based capillary hydrogels (ACH) support peripheral nervous system derived axon
      growth, which is accompanied by glial supporting cell migration into the ACH. The
      aim of the present study was to analyze central nervous system (CNS) derived
      (entorhinal cortex, spinal cord slice cultures) axon regrowth into ACH containing
      linearly aligned capillaries of defined capillary sizes without and with gelatin
      constituent. Anisotropic ACH were prepared by ionotropic gel formation using
      Ba(2+), Cu(2+), Sr(2+), or Zn(2+) ions resulting in gels with average capillary
      diameters of 11, 13, 29, and 89MUm, respectively. Postnatal rat entorhinal cortex
      or spinal cord slice cultures were placed on top of 500MUm thick ACH. Seven days
      later axon growth and astroglial migration into the ACH were determined. Axon
      density within capillaries correlated positively with increasing capillary
      diameters, whereas longitudinally oriented axon outgrowth diminished with
      increasing capillary diameter. Axons growing into the hydrogels were always
      accompanied by astrocytes strongly suggesting that respective cells are required
      to mediate CNS axon elongation into ACH. Overall, midsize capillary diameter ACH
      appeared to be the best compromise between axon density and orientation. Taken
      together, ACH promote CNS axon ingrowth, which is determined by the capillary
      diameter and migration of slice culture derived astroglia into the hydrogel.
      STATEMENT OF SIGNIFICANCE: Biomaterials are investigated as therapeutic tools to
      bridge irreversible lesions following traumatic spinal cord injury. The goal is
      to develop biomaterials, which promote longitudinally oriented regeneration of as
      many injured axons as possible as prerequisite for substantial functional
      recovery. Optimal parameters of the biomaterial have yet to be defined. In the
      present study we show that increasing capillary diameters within such hydrogels
      enhanced central nervous system axon regeneration at the expense of longitudinal
      orientation. Axon ingrowth into the hydrogels was only observed in the presence
      of glial supporting cells, namely astrocytes. This suggests that alginate-based
      hydrogels need to be colonized with respective cells in order to facilitate axon
      ingrowth.

PMID- 26310677
TI  - Early Lessons From a Worldwide, Multicenter, Followup Study of the Recalled
      Articular Surface Replacement Hip System.
AB  - BACKGROUND: Adverse local tissue reactions (ALTRs) around hip arthroplasties are
      an important reason for failure of metal-on-metal (MoM) hip implants. Little is
      known about capsular dehiscence patterns as ALTRs decompress from the hip into
      the surrounding tissue planes; these patterns may also influence the onset and
      severity of patient symptoms. QUESTIONS/PURPOSES: Through a multicenter study
      approach, we asked: (1) Is ALTR location related to the surgical approach used
      for arthroplasty in patients who underwent hip arthroplasty (resurfacing or THA)
      with a single, recalled hip arthroplasty system? (2) Do ALTR severity and
      location affect patient-reported outcomes in these patients? (3) Is ALTR severity
      different between patients who received the resurfacing version of this component
      (Articular Surface Replacement [ASR]) and those who received the THA implant in
      this system (ASR XL)? METHODS: In a multicenter prospective study of patients who
      had undergone surgery with use of the ASR and ASR XL hip system (DePuy
      Orthopaedics, Warsaw, IN, USA), 288 patients (333 hips) from two centers had a
      metal artifact reduction sequence MRI of the hip performed at a mean time of 6
      years postsurgery. Procedures included 166 hips (50%) with ASR resurfacing and
      167 hips (50%) with ASR XL THA performed between 2004 and 2010. One hundred
      twenty-nine hips (39%) had been operated on using a direct lateral approach and
      204 using a posterior approach (61%). The EQ-5D, Harris hip score, UCLA activity
      score, and visual analog scale pain score were obtained for each patient. ALTRs
      were classified using the Anderson ALTR grading system, and the location,
      synovial thickness, and diameter of the ATLRs were assessed. The relationship
      between ALTR location and surgical approach as well as for ALTR severity and
      patient-reported outcomes were evaluated, and logistic regression was used to
      identify predictors for moderate-to-severe ALTRs. RESULTS: Moderate or severe
      ALTRs were identified in 79 hips (24%); 41 of these hips had been operated on
      using the direct lateral approach and 38 using the posterior approach. In
      patients in whom the lateral approach was used, 83% had an anterior ALTR.
      Similarly, 71% of patients in the posterior approach group had posterior ALTRs.
      There were no differences in patient-reported outcome measures between patients
      with moderate-to-severe ALTRs and those with no ALTR findings on MRI (p > 0.09).
      Use of ASR XL was an independent risk factor for moderate-to-severe ALTRs (odds
      ratio, 2.8; 95% confidence interval, 1.4-5.5 p = 0.004) and patients with ASR XL
      also had a thicker synovium (median ASR XL = 3.6 mm [1.2-10.6 mm], median ASR =
      2.6 mm [1.2-10.7 mm], p < 0.001) and larger maximal ALTR diameter (median ASR XL
      = 47.6 mm [14-109.70 mm], median ASR = 38.4 [17.2-118.0 mm], p = 0.02) than
      patients treated with ASR. CONCLUSIONS: The location of ALTRs can be predicted
      based on the previous surgical approach to the hip. Patients with ASR XL are more
      likely to develop moderate-to-severe ALTRs compared with ASR patients. An
      extensive range of patient-reported outcome measures may not identify all
      patients with ALTRs further supporting the use of MRI as a screening measure for
      ALTRs. LEVEL OF EVIDENCE: Level II, therapeutic study.

PMID- 26310678
TI  - CORR Insights((r)): D-amino acid inhibits biofilm but not new bone formation in
      an ovine model.

PMID- 26310679
TI  - CORR Insights((r)): Should High-grade Extraosseous Osteosarcoma Be Treated With
      Multimodality Therapy Like Other Soft Tissue Sarcomas?

PMID- 26310680
TI  - Implant Design Variations in Reverse Total Shoulder Arthroplasty Influence the
      Required Deltoid Force and Resultant Joint Load.
AB  - BACKGROUND: Reverse total shoulder arthroplasty (RTSA) is widely used; however,
      the effects of RTSA geometric parameters on joint and muscle loading, which
      strongly influence implant survivorship and long-term function, are not well
      understood. By investigating these parameters, it should be possible to
      objectively optimize RTSA design and implantation technique. QUESTIONS/PURPOSES:
      The purposes of this study were to evaluate the effect of RTSA implant design
      parameters on (1) the deltoid muscle forces required to produce abduction, and
      (2) the magnitude of joint load and (3) the loading angle throughout this motion.
      We also sought to determine how these parameters interacted. METHODS: Seven
      cadaveric shoulders were tested using a muscle load-driven in vitro simulator to
      achieve repeatable motions. The effects of three implant parameters-humeral
      lateralization (0, 5, 10 mm), polyethylene thickness (3, 6, 9 mm), and
      glenosphere lateralization (0, 5, 10 mm)-were assessed for the three outcomes:
      deltoid muscle force required to produce abduction, magnitude of joint load, and
      joint loading angle throughout abduction. RESULTS: Increasing humeral
      lateralization decreased deltoid forces required for active abduction (0 mm: 68%
      +/- 8% [95% CI, 60%-76% body weight (BW)]; 10 mm: 65% +/- 8% [95% CI, 58%-72 %
      BW]; p = 0.022). Increasing glenosphere lateralization increased deltoid force (0
      mm: 61% +/- 8% [95% CI, 55%-68% BW]; 10 mm: 70% +/- 11% [95% CI, 60%-81% BW]; p =
      0.007) and joint loads (0 mm: 53% +/- 8% [95% CI, 46%-61% BW]; 10 mm: 70% +/- 10%
      [95% CI, 61%-79% BW]; p < 0.001). Increasing polyethylene cup thickness increased
      deltoid force (3 mm: 65% +/- 8% [95% CI, 56%-73% BW]; 9 mm: 68% +/- 8% [95% CI,
      61%-75% BW]; p = 0.03) and joint load (3 mm: 60% +/- 8% [95% CI, 53%-67% BW]; 9
      mm: 64% +/- 10% [95% CI, 56%-72% BW]; p = 0.034). CONCLUSIONS: Humeral
      lateralization was the only parameter that improved joint and muscle loading,
      whereas glenosphere lateralization resulted in increased loads. Humeral
      lateralization may be a useful implant parameter in countering some of the
      negative effects of glenosphere lateralization, but this should not be considered
      the sole solution for the negative effects of glenosphere lateralization.
      Overstuffing the articulation with progressively thicker humeral polyethylene
      inserts produced some adverse effects on deltoid muscle and joint loading.
      CLINICAL RELEVANCE: This systematic evaluation has determined that glenosphere
      lateralization produces marked negative effects on loading outcomes; however, the
      importance of avoiding scapular notching may outweigh these effects. Humeral
      lateralization's ability to decrease the effects of glenosphere lateralization
      was promising but further investigations are required to determine the effects of
      combined lateralization on functional outcomes including range of motion.

PMID- 26310681
TI  - CORR Insights((r)): Which Fixation Device is Preferred for Surgical Treatment of
      Intertrochanteric Hip Fractures in the United States? A Survey of Orthopaedic
      Surgeons.

PMID- 26310682
TI  - CORR Insights((r)): What Are Risk Factors for Intraoperative Humerus Fractures
      During Revision Reverse Shoulder Arthroplasty and Do They Influence Outcomes?

PMID- 26310683
TI  - CORR Insights((r)): does cup-cage reconstruction with oversized cups provide
      initial stability in THA for osteoporotic acetabular fractures?

PMID- 26310684
TI  - [Evaluation of inappropriate prescriptions on patients over 65 years old in a
      third level hospital].

PMID- 26310685
TI  - Are there reliable indicators predicting post-operative complications in acute
      appendicitis?
AB  - PURPOSE: To clarify the predictors of post-operative complications of pediatric
      acute appendicitis. METHODS: The medical records of 485 patients with acute
      appendicitis operated on between January 2006 and November 2014 were
      retrospectively reviewed. Age, sex, preoperative WBC, CRP, and appendix maximum
      short diameter on diagnostic imaging (AMSD) were compared retrospectively with
      the complications group (Group C) vs the non-complication group (Group NC) by
      Student's T test, Fisher exact test and Multivariate analysis. Regression
      analysis with p less than 0.01 was considered significant. We analyzed the most
      recent 314 laparoscopic appendectomy patients similarly. RESULTS: Complications
      were found in 29 of the 485 appendectomies (6.0%). Comparing Group C to Group NC,
      preoperative WBC (*10(3)/MUl) 16.4 +/- 5.6 vs 14.1 +/- 4.1 (p < 0.01), CRP
      (mg/dl) 8.3 +/- 7.1 vs 3.3 +/- 4.6 (p < 0.01), AMSD (mm) was 12.1 +/- 3.7 vs 9.9
      +/- 2.8 (p < 0.01). The CRP was significantly different by Multivariate analysis,
      but the WBC and AMSD wasn't. The results following laparoscopic appendicectomy
      data were identical. CONCLUSION: Preoperative WBC, CPR and AMSD all indicated an
      increased risk of complications. If WBC (/MUl) >16,500, CRP >3.1 mg/dl and AMSD
      >11.4 mm, complications increased sixfold.

PMID- 26310687
TI  - Experts split on 21st Century Cures Act.

PMID- 26310686
TI  - A validation of the pain interference index in adults with long-standing pain.
AB  - BACKGROUND: Chronic pain is a major health problem and more knowledge is needed
      regarding the interference of pain on behaviors in different life domains.
      Clinically useful and statistically sound pain interference measures are highly
      important. Studies on youths have shown that the Pain Interference Index (PII) is
      a reliable and valid instrument that is sensitive to change following behavioral
      treatment. This measure may also have utility for adults, but no study has so far
      evaluated the statistical properties of the PII for long-standing pain in adults.
      METHODS: Data were collected from 239 consecutive adults with non-specific
      chronic pain referred to a tertiary pain clinic. We investigated the factor
      structure of items using a principal component analysis. Cronbach's alpha was
      calculated to assess internal consistency. The questionnaire's ability to predict
      levels of, e.g., disability was analyzed by means of regression analyses.
      RESULTS: Analyses illustrated the adequacy of a one-factor solution with six
      items. Cronbach's alpha (0.85) suggested a satisfactory internal consistency
      among items. The PII explained significant amounts of variance in pain
      disability, physical, and mental health-related quality of life and depression,
      suggesting concurrent criteria validity. CONCLUSION: The PII is a brief
      questionnaire with reliable and valid statistical properties to assess pain
      interference in adults. Other studies support the reliability and validity of PII
      for use with youths, and now the PII can be used to analyze the influence of pain
      on behaviors across age groups. Potentially, the PII can also be used as an
      outcome measure in clinical trials.

PMID- 26310688
TI  - Early promise for infant RSV vaccine development.

PMID- 26310689
TI  - Lung function trajectories differ in patients with COPD.

PMID- 26310690
TI  - Endoscopic endonasal resection of esthesioneuroblastoma: A single center
      experience of 24 patients.
AB  - OBJECTIVE: Esthesioneuroblastoma (ENB) is an uncommon malignant tumor. During the
      past decade, endoscopic approaches have been gradually applied in treating skull
      base tumors. However, the experience in using this approach to treat ENB is still
      limited. Kadish staging and Dulguerov staging are common methods used for ENB
      staging, but it remains unclear as to which method is better. In this study, we
      reviewed our experiences with endoscopic surgeries for ENB and analyzed the
      prognostic roles of the two staging methods. METHODS: A total of 24 patients with
      ENB treated with only endoscopic endonasal surgery between January 2001 and March
      2012 were included. Overall survival (OS) and disease-free survival (DFS) were
      analyzed using the Kaplan-Meier method and early and advanced stages were
      compared using the log-rank test. The prognostic roles of the two staging methods
      were also analyzed. RESULTS: Amongst the 24 patients, 19 patients presented with
      newly diagnosed ENB, and 5 patients presented with recurrent disease. The three
      year OS and DFS rates were 82% and 70.8%, respectively. Four patients (16.6%)
      died from recurrence of the tumor. Dulguerov staging predicted OS with
      significant differences (P=0.042), whereas Kadish staging predicted DFS with
      significant differences (P=0.020) between the early and advanced stages.
      CONCLUSIONS: The present study showed experiences that purely endoscopic
      endonasal surgery for ENB showed successful survival results with remarkably
      decreased complications. Dulguerov staging and Kadish staging play different
      prognostic roles in patients treated with purely endoscopic endonasal resection
      based on various end points.

PMID- 26310691
TI  - The Presence and Consequence of Nonalbuminuric Chronic Kidney Disease in Patients
      With Type 1 Diabetes.
AB  - OBJECTIVE: This study investigated the prevalence of nonalbuminuric chronic
      kidney disease in type 1 diabetes to assess whether it increases the risk of
      cardiovascular and renal outcomes as well as all-cause mortality. RESEARCH DESIGN
      AND METHODS: This was an observational follow-up of 3,809 patients with type 1
      diabetes from the Finnish Diabetic Nephropathy Study. All patients were
      Caucasians and thoroughly examined at baseline. Their mean age was 37.6 +/- 11.8
      years and duration of diabetes 21.2 +/- 12.1 years. Follow-up data on
      cardiovascular and renal outcomes and mortality were retrieved from registers.
      During 13 years of median follow-up, 378 developed end-stage renal disease, 415
      suffered an incident cardiovascular event, and 406 died. RESULTS: At baseline, 78
      (2.0%) had nonalbuminuric chronic kidney disease. This was associated with older
      age, female sex, history of retinal laser treatment, cardiovascular events, and
      the number of antihypertensive drugs in use, but not with blood pressure levels
      or specific antihypertensive agents. Nonalbuminuric chronic kidney disease did
      not increase the risk of albuminuria (hazard ratio [HR] 2.0 [95% CI 0.9-4.4]) or
      end-stage renal disease (HR 6.4 [0.8-53.0]) but did increase the risk of
      cardiovascular events (HR 2.0 [1.4-3.5]) and all-cause mortality (HR 2.4 [1.4
      3.9]). The highest risk of cardiovascular and renal end points was observed in
      the patients with albuminuria. CONCLUSIONS: Nonalbuminuric chronic kidney disease
      is not a frequent finding in patients with type 1 diabetes, but when present, it
      is associated with an increased risk of cardiovascular morbidity and all-cause
      mortality but not with renal outcomes.

PMID- 26310692
TI  - Safety and Efficacy of Omarigliptin (MK-3102), a Novel Once-Weekly DPP-4
      Inhibitor for the Treatment of Patients With Type 2 Diabetes.
AB  - OBJECTIVE: This study was conducted to determine the optimal dose of
      omarigliptin, a once-weekly (q.w.) dipeptidyl peptidase IV (DPP-4) inhibitor, for
      the treatment of patients with type 2 diabetes and evaluate the long-term safety
      of that dose. RESEARCH DESIGN AND METHODS: In a multicenter, double-blind, 12
      week, dose-range finding study, 685 oral antihyperglycemic agent-naive or washed
      out subjects with type 2 diabetes were randomized to one of five once-weekly
      doses of omarigliptin (0.25 mg, 1 mg, 3 mg, 10 mg, or 25 mg) or placebo. The
      primary efficacy end point was change from baseline in HbA1c, and secondary end
      points were 2-h postmeal glucose (PMG) and fasting plasma glucose (FPG). Analysis
      included all patients who received at least one dose of the study medication.
      Subjects who completed the base study were eligible to enter a 66-week extension
      study. RESULTS: Once-weekly treatment for 12 weeks with omarigliptin provided
      dose-related reductions in HbA1c, 2-h PMG, and FPG. At week 12, the omarigliptin
      25-mg dose provided the greatest glycemic efficacy. The placebo-adjusted least
      squares mean reductions from baseline in HbA1c, 2-h PMG, and FPG were -0.72% (
      7.8 mmol/mol), -2.5, and -1.3 mmol/L, respectively (all P < 0.001). The incidence
      of adverse events was similar across dose groups, with a low incidence of
      symptomatic hypoglycemia and no effect on body weight. Omarigliptin was generally
      well-tolerated throughout the base and extension studies. CONCLUSIONS:
      Omarigliptin 25 mg q.w., compared with placebo, provided significant glucose
      lowering and was generally well tolerated for up to 78 weeks in patients with
      type 2 diabetes.

PMID- 26310693
TI  - Anti-PD1 Pembrolizumab Can Induce Exceptional Fulminant Type 1 Diabetes.

PMID- 26310694
TI  - Brokering the Research-Practice Gap: A typology.
AB  - Despite widespread recognition of a research-practice gap in multiple service
      sectors, less is known about how pre-existing communication channels facilitate
      the flow of information between researchers and practitioners. In the current
      study, we applied an existing typology of brokerage developed by Gould and
      Fernandez (Sociol Methodol 19:89-126, 1989) to examine what types of brokerage
      facilitate information spread between researchers and educational practitioners.
      Specifically, we conducted semi-structured interviews with 19 school
      administrators and staff in two public school districts regarding their
      experiences searching for information about instructional, health, and social
      skills programs. Using deductive content analysis, we found evidence of all five
      types of brokerage identified by Gould and Fernandez (1989). However, only three
      types of brokerage-gatekeepers, representatives, and liaisons-were involved in
      the flow of information between school administrators and researchers. Moreover,
      information transfer often occurred in longer chains that involved multiple,
      distinct types of brokerage. We conclude with the broad implications of our
      findings for narrowing the research-practice gap by improving researchers'
      dissemination efforts and practitioners' search for information.

PMID- 26310695
TI  - Limited efficacy of HLA-haploidentical peripheral blood stem cell infusion in
      treatment of elderly patients with acute myelogenous leukaemia.

PMID- 26310696
TI  - Surgical site infection impact of pelvic exenteration procedure.
AB  - BACKGROUND: We sought to investigate morbidity and infectious complications
      following pelvic exenteration (PEx) and compare infectious complications of
      patients undergoing PEx and conventional rectal resections. METHODS: The NSQIP
      database was utilized to examine the clinical data of patients undergoing
      elective rectal resections during 2005-2013. Multivariate regression analysis was
      used to compare postoperative complications of patients who underwent PEx and
      proctectomy procedure. RESULTS: We sampled a total of 7,950 patients who
      underwent rectal resection. Of these, 303 (3.8%) patients underwent pelvic
      exenteration. Mortality, morbidity, and infectious complications of patients who
      underwent pelvic exenteration were 1.7%, 65.7%, and 42.6%, respectively. Patients
      who underwent PEx had a significantly higher rate of morbidity (AOR: 2.01, P <
      0.01), overall infectious complications (AOR: 1.49, P < 0.01), hemorrhagic
      complications (AOR: 3.36, P < 0.01), and surgical site infections (SSI) (AOR:
      1.23, P = 0.04) compared to patients who underwent proctectomy. Return to
      operation room (AOR: 4.99, P < 0.01), obesity (AOR: 1.43, P < 0.01), disseminated
      cancer (AOR: 1.30, P = 0.01) were significantly associated with SSI
      complications. CONCLUSION: Postoperative morbidity and infectious complication
      are significantly higher after PEx procedure. Return to operation room, obesity,
      and disseminated cancer are strongly associated with surgical site infections
      complications in rectal surgery. Specific consideration to infectious
      complications is recommended for these patients.

PMID- 26310698
TI  - Pollen limitation and its influence on natural selection through seed set.
AB  - Stronger pollen limitation should increase competition among plants, leading to
      stronger selection on traits important for pollen receipt. The few explicit tests
      of this hypothesis, however, have provided conflicting support. Using the
      arithmetic relationship between these two quantities, we show that increased
      pollen limitation will automatically result in stronger selection (all else
      equal) although other factors can alter selection independently of pollen
      limitation. We then tested the hypothesis using two approaches. First, we
      analysed the published studies containing information on both pollen limitation
      and selection. Second, we explored how natural selection measured in one Ontario
      population of Lobelia cardinalis over 3 years and two Michigan populations in 1
      year relates to pollen limitation. For the Ontario population, we also explored
      whether pollinator-mediated selection is related to pollen limitation. Consistent
      with the hypothesis, we found an overall positive relationship between selection
      strength and pollen limitation both among species and within L. cardinalis.
      Unexpectedly, this relationship was found even for vegetative traits among
      species, and was not found in L. cardinalis for pollinator-mediated selection on
      nearly all trait types. 

PMID- 26310697
TI  - The Trp53 delta proline (Trp53DeltaP) mouse exhibits increased genome instability
      and susceptibility to radiation-induced, but not spontaneous, tumor development.
AB  - The tumor suppressor TP53 can initiate a plethora of anti-proliferative effects
      to maintain genomic integrity under conditions of genotoxic stress. The N
      terminal proline-rich domain (PRD) of TP53 is important in the regulation of TP53
      activity and stability. A common polymorphism at codon 72 in this region has been
      associated with altered cancer risk in humans. The Trp53DeltaP mouse, which
      carries a germline homozygous deletion of a region of the PRD, does not develop
      spontaneous tumors in a mixed 129/Sv and C57BL/6 genetic background, but is
      highly susceptible to a broad range of tumor types following total body exposure
      to 4 Gy gamma (gamma) radiation. This contrasts with the tumor spectrum in Trp53
      null (-/-) mice, which mainly develop thymic lymphomas and osteosarcomas.
      Analysis of genomic instability in tissues and cells from Trp53DeltaP mice
      demonstrated elevated basal levels of aneuploidy, but this is not sufficient to
      drive spontaneous tumorigenesis, which requires an additional DNA damage
      stimulus. Levels of genomic instability did not increase significantly in
      Trp53DeltaP mice following irradiation exposure, suggesting that other radiation
      effects including tissue inflammation, altered metabolism or autophagy, may play
      an important role. The Trp53DeltaP mouse is a novel model to dissect the
      mechanisms of tumor development induced by radiation exposure. (c) 2015 Wiley
      Periodicals, Inc.

PMID- 26310699
TI  - Oxidoreductases provide a more generic response to metallic stressors (Cu and Cd)
      than hydrolases in soil fungi: new ecotoxicological insights.
AB  - The present study investigates the effect of metals on the secretion of enzymes
      from 12 fungal strains maintained in liquid cultures. Hydrolases (acid
      phosphatase, beta-glucosidase, beta-galactosidase, and N-acetyl-beta
      glucosaminidase) and ligninolytic oxidoreductases (laccase, Mn, and lignin
      peroxidases) activities, as well as biomass production, were measured in culture
      fluids from fungi exposed to Cu or Cd. Our results showed that all fungi secreted
      most of the selected hydrolases and that about 50% of them produced a partial
      oxidative system in the absence of metals. Then, exposure of fungi to metals led
      to the decrease in biomass production. At the enzymatic level, Cu and Cd modified
      the secretion profiles of soil fungi. The response of hydrolases to metals was
      contrasted and complex and depended on metal, enzyme, and fungal strain
      considered. By contrast, the metals always stimulated the activity of
      ligninolytic oxidoreductases in fungal strains. In some of them, oxidoreductases
      were specifically produced following metal exposure. Fungal oxidoreductases
      provide a more generic response than hydrolases, constituting thus a
      physiological basis for their use as biomarkers of metal exposure in soils.

PMID- 26310701
TI  - Phytoremediation of carbamazepine and its metabolite 10,11-epoxycarbamazepine by
      C3 and C4 plants.
AB  - The anticonvulsant drug carbamazepine is considered as an indicator of sewage
      water pollution: however, its uptake by plants and effect on metabolism have not
      been sufficiently documented, let alone its metabolite (10,11
      epoxycarbamazepine). In a model system of sterile, hydroponically cultivated Zea
      mays (as C4 plant) and Helianthus annuus (as C3 plant), the uptake and effect of
      carbamazepine and 10,11-epoxycarbamazepine were studied in comparison with those
      of acetaminophen and ibuprofen. Ibuprofen and acetaminophen were effectively
      extracted from drug-supplemented media by both plants, while the uptake of more
      hydrophobic carbamazepine was much lower. On the other hand, the carbamazepine
      metabolite, 10,11-epoxycarbamazepine, was, unlike sunflower, willingly taken up
      by maize plants (after 96 h 88 % of the initial concentration) and effectively
      stored in maize tissues. In addition, the effect of the studied pharmaceuticals
      on the plant metabolism (enzymes of Hatch-Slack cycle, peroxidases) was followed.
      The activity of bound peroxidases, which could cause xylem vessel lignification
      and reduction of xenobiotic uptake, was at the level of control plants in maize
      leaves contrary to sunflower. Therefore, our results indicate that maize has the
      potential to remove 10,11-epoxycarbamazepine from contaminated soils. 

PMID- 26310700
TI  - Environmental microbiology as a mosaic of explored ecosystems and issues.
AB  - Microbes are phylogenetically (Archaea, Bacteria, Eukarya, and viruses) and
      functionally diverse. They colonize highly varied environments and rapidly
      respond to and evolve as a response to local and global environmental changes,
      including those induced by pollutants resulting from human activities. This
      review exemplifies the Microbial Ecology EC2CO consortium's efforts to explore
      the biology, ecology, diversity, and roles of microbes in aquatic and continental
      ecosystems. 

PMID- 26310702
TI  - Performance of a pilot demonstration-scale hybrid constructed wetland system for
      on-site treatment of polluted urban river water in Northwestern China.
AB  - Hybrid constructed wetland (HCW) systems have been used to treat various
      wastewaters across the world. However, large-scale applications of HCWs are
      scarce, particularly for on-site improvement of the water quality of highly
      polluted urban rivers in semi-arid regions. In this study, a large pilot-scale
      HCW system was constructed to improve the water quality of the Zaohe River in
      Xi'an, China. With a total area of about 8000 m(2), the pilot HCW system,
      composed of different configurations of surface and subsurface flow wetlands, was
      operated for 2 years at an average inflow volume rate of 362 m(3)/day. Local
      Phragmites australis and Typha orientalis from the riverbank were planted in the
      HCW system. Findings indicate a higher treatment efficiency for organics and
      suspended solids than nutrients. The inflow concentrations of 5-day biochemical
      oxygen demand (BOD5), chemical oxygen demand (COD), suspended solids (SS), total
      nitrogen (TN), NH3-N, and total phosphorus (TP) were 125.6, 350.9, 334.2, 38.5,
      27.2, and 3.9 mg/L, respectively. Average removal efficiencies of 94.4, 74.5,
      92.0, 56.3, 57.5, and 69.2%, respectively, were recorded. However, the pollutant
      removal rates were highly seasonal especially for nitrogen. Higher removals were
      recorded for all pollutants in the autumn while significantly lower removals were
      recorded in the winter. Plant uptake and assimilation accounted for circa 19-29
      and 16-23% of the TN and TP removal, respectively. Moreover, P. australis
      demonstrated a higher nutrient uptake ability and competitive potential. Overall,
      the high efficiency of the pilot HCW for improving the water quality of such a
      highly polluted urban river provided practical evidence of the applicability of
      the HCW technology for protecting urban water environments.

PMID- 26310703
TI  - Potential toxicity of environmentally relevant perfluorooctane sulfonate (PFOS)
      concentrations to yellow-legged gull Larus michahellis embryos.
AB  - Perfluooctane sulfonate (PFOS) is considered an emerging pollutant because of its
      wide distribution in both aquatic and terrestrial ecosystems, as well as its
      potential toxicity to living organisms. Although PFOS environmental levels and
      the adverse effects on classical model organisms in toxicological studies are
      well known, including developmental alterations and alteration of oxidative
      status, its toxicity to free-living species has been seldom investigated. The aim
      of this study was to assess the potential toxicity of environmental levels of
      PFOS to yellow-legged gull (Larus michahellis) embryos under field experimental
      conditions. In a within-clutch experimental design, we injected two PFOS
      concentrations (100 ng PFOS/g egg weight and 200 ng PFOS/g egg weight) in ovo
      soon after laying. Eggs were collected when they reached the cracking stage. We
      investigated the effects of PFOS treatment, laying order and sex on both
      morphological and biochemical endpoints of embryos. Specifically, we assessed
      changes in embryo body mass and tarsus length, as well as in liver and brain
      mass. Moreover, the imbalance of oxidative status was evaluated in both liver and
      brain from embryos by measuring total antioxidant capacity (TAC) and total
      oxidant status (TOS), while the levels of protein carbonyl content (PCO) and DNA
      fragmentation were measured as oxidative and genetic damage endpoints,
      respectively. The concentrations of PFOS we tested did not significantly alter
      the morphological endpoints, independently of laying order and sex. Similarly,
      embryo oxidative status and oxidative and genetic damage were not significantly
      affected by PFOS in ovo exposure. These findings suggest that current
      environmental PFOS levels do not affect early development of yellow-legged gull
      embryos. 

PMID- 26310704
TI  - Temporal trends and risk assessment of polychlorinated biphenyls and heavy metals
      in a solid waste site in Taizhou, China.
AB  - The solid wastes generated during the production of chemicals are important
      sources of polychlorinated biphenyls (PCBs) and heavy metals. However, few
      studies have been conducted regarding long-term monitoring of the risks and
      states of PCBs and heavy metal pollution from these sources. Herein, we reported
      the concentrations and risks posed by these pollutants at a chemical solid waste
      storage site in Taizhou, China, based on data collected before (in 2006) and
      after clearing the solid waste (in 2013). We examined the concentrations of 24
      PCBs, including ten dioxin-like-PCB (DL-PCB) congeners (PCB77, 105, 114, 118,
      123, 126, 156, 167, 169, and 189). Our data showed that the mean ?24PCB
      concentrations in the soil, water, and plant samples were 6902.90 ng/g, 1637.58
      ng/L, and 33.95 ng/g, respectively, in 2013. Furthermore, Cr was the most
      prevalent contaminant. The hazard quotient (HQ) values showed that Pb posed the
      highest risk in the soil samples, followed by Hg. The results of the reporter
      gene assay showed that soil extracts from S1, S2, S3, S4, S5, S6, and S9
      exhibited potential estrogenic activities. A comparison of the data showed that
      the PCB pollution in some sites of this area was still serious. The data provided
      here are fundamentally useful for policy makers to regulate this type of storage
      site.

PMID- 26310705
TI  - An integrated optimization method for river water quality management and risk
      analysis in a rural system.
AB  - In this study, an interval-stochastic-based risk analysis (RSRA) method is
      developed for supporting river water quality management in a rural system under
      uncertainty (i.e., uncertainties exist in a number of system components as well
      as their interrelationships). The RSRA method is effective in risk management and
      policy analysis, particularly when the inputs (such as allowable pollutant
      discharge and pollutant discharge rate) are expressed as probability
      distributions and interval values. Moreover, decision-makers' attitudes towards
      system risk can be reflected using a restricted resource measure by controlling
      the variability of the recourse cost. The RSRA method is then applied to a real
      case of water quality management in the Heshui River Basin (a rural area of
      China), where chemical oxygen demand (COD), total nitrogen (TN), total phosphorus
      (TP), and soil loss are selected as major indicators to identify the water
      pollution control strategies. Results reveal that uncertainties and risk
      attitudes have significant effects on both pollutant discharge and system
      benefit. A high risk measure level can lead to a reduced system benefit; however,
      this reduction also corresponds to raised system reliability. Results also
      disclose that (a) agriculture is the dominant contributor to soil loss, TN, and
      TP loads, and abatement actions should be mainly carried out for paddy and dry
      farms; (b) livestock husbandry is the main COD discharger, and abatement measures
      should be mainly conducted for poultry farm; (c) fishery accounts for a high
      percentage of TN, TP, and COD discharges but a has low percentage of overall net
      benefit, and it may be beneficial to cease fishery activities in the basin. The
      findings can facilitate the local authority in identifying desired pollution
      control strategies with the tradeoff between socioeconomic development and
      environmental sustainability. 

PMID- 26310706
TI  - Detoxification effects of phytonutrients against environmental toxicants and
      sharing of clinical experience on practical applications.
AB  - According to the Food and Health Bureau and Trade and Industry Department of the
      Hong Kong Government, 90 % of the total food supply in Hong Kong was imported
      from the Mainland China. In addition, the hidden or illegal use of prohibited
      pesticides, food adulteration (e.g., using industrial salt in food processing,
      using gutter oil as cooking oil), and pollutions were periodically reported by
      the media. Excessive exposure to toxic heavy metals or persistent organic
      pollutants (POPs) from diet or environmental is inevitable amid industrialization
      and pollution. Understanding of the detoxification ability among nutrients in
      plant-based food (i.e., phytonutrients in green tea, onion, garlic, coriander,
      and turmeric) offers therapeutic and preventive effects against the poisoning
      effects due to these pollutants. Oxidative stress and pro-inflammatory actions
      are the common mechanisms for heavy metals or POPs toxicities, while
      phytonutrients counteracts these cellular insults by anti-oxidation, upregulation
      of anti-inflammatory pathways, and chelation.

PMID- 26310707
TI  - Screening of phthalate esters in 47 branded perfumes.
AB  - In the last few years, the use of phthalates in perfumes has gained attention
      because these chemicals are sometimes added intentionally as a solvent and a
      fixative. Five phthalate esters, dimethyl phthalate (DMP), diethyl phthalate
      (DEP), dibutyl phthalate (DBP), benzyl butyl phthalate (BBP), and diethyl hexyl
      phthalate (DEHP), were measured in 47 branded perfumes using headspace solid
      phase microextraction (SPME) followed by gas chromatography-mass spectrometry (GC
      MS). The results revealed considerable amounts of phthalate in all 47 brands with
      detection frequencies > limit of quantitation in the following order: DEP (47/47)
      > DMP (47/47) > BBP (47/47) > DEHP (46/47) > DBP (23/45). Of the 47 brands, 68.1,
      72.3, 85.1, 36.2, and 6.7 % had DEP, DMP, BBP, DEHP, and DBP levels,
      respectively, above their reported threshold limits. Of these phthalates, DEP was
      found to have the highest mean value (1621.625 ppm) and a maximum of 23,649.247
      ppm. The use of DEP in the perfume industry is not restricted because it does not
      pose any known health risks for humans. DMP had the second highest level detected
      in the perfumes, with a mean value of 30.202 ppm and a maximum of 405.235 ppm.
      Although DMP may have some uses in cosmetics, it is not as commonly used as DEP,
      and again, there are no restrictions on its use. The levels of BBP were also
      high, with a mean value of 8.446 ppm and a maximum of 186.770 ppm. Although the
      EU banned the use of BBP in cosmetics, 27 of the tested perfumes had BBP levels
      above the threshold limit of 0.1 ppm. The mean value of DEHP found in this study
      was 5.962 ppm, and a maximum was 147.536 ppm. In spite of its prohibition by the
      EU, 7/28 perfumes manufactured in European countries had DEHP levels above the
      threshold limit of 1 ppm. The DBP levels were generally low, with a mean value of
      0.0305 ppm and a maximum value of 0.594 ppm. The EU banned the use of DBP in
      cosmetics; however, we found three brands that were above the threshold limit of
      0.1 ppm, and all were manufactured in European countries. The results of this
      study are alarming and definitely need to be brought to the attention of the
      public and health regulators. Although some phthalate compounds are still used in
      cosmetics, many scientists and environmental activists have argued that
      phthalates are endocrine-disrupting chemicals that have not been yet proven to be
      safe for any use, including cosmetics. Phthalates may also have different degrees
      of estrogenic modes of action. Furthermore, we should not dismiss the widespread
      use of phthalates in everyday products and exposure to these chemicals from
      sources such as food, medications, and other personal care products.

PMID- 26310708
TI  - Microwave-hydrothermal method for the synthesis of composite materials for
      removal of arsenic from water.
AB  - Composite material Zr-doped TiO2, suitable for the removal of arsenic from water,
      was synthetized with fast and simple microwave-hydrothermal method. Obtained
      material, Zr-TiO2, had uniform size and composition with zirconium ions
      incorporated into crystal structure of titanium dioxide. Synthetized composite
      material had large specific surface area and well-developed micropore and
      mesopore structure that was responsible for fast adsorption of As(III) and As(V)
      from water. The influence of pH on the adsorption capacity of arsenic was
      studied. The kinetics and isotherm experiments were also performed. The treatment
      of natural water sample containing high concentration of arsenic with composite
      material Zr-TiO2 was efficient. The concentration of arsenic was reduced to the
      value recommended by WHO. 

PMID- 26310709
TI  - A multilevel analysis of factors influencing the flow efficiency of the cataract
      surgery process in hospitals.
AB  - PURPOSE: To detect factors contributing to variation in cataract surgery
      processes. METHODS: A multilevel study was conducted to compare the process of
      cataract surgery between hospitals in Belgium. The main data were collected
      through non-participative observations and time measurements in four hospitals.
      Surgeons (n = 16) performing cataract surgery in the selected region and their
      patients (n = 274) undergoing cataract surgery were observed. Flow efficiency is
      measured in the operating room (OR) as time for preparation, surgery, exit and
      turnover. RESULTS: Flow efficiency in the OR can be negatively influenced by the
      severity of the cataract [+2.778 (1.139) min in preparation time (p < 0.05);
      +4.616 (1.786) min in surgery time when severe cataract (p < 0.05)] and the
      presence of special-cause variation [+2.832 (1.893) min preparation time (p <
      0.05); +2.503 (1.277) min surgery time (p < 0.05); +1.181 (0.350) min exit time
      (p <= 0.001)]. Administering topical analgesia instead of peribulbar [+13.548
      (4.436) min preparation time (p <= 0.001)], retrobulbar [+3.856 (1.548) min
      surgery time (p <= 0.05)] or general analgesia [+5.617 (2.536) min surgery time
      (p < 0.05); +5.175 (0.817) min exit time (p <= 0.001)] enhances flow efficiency.
      The experience of surgeons (>15 years) impacts flow efficiency [+12.838 (5.922)
      min surgery time when low experience]. The volume of cataracts performed annually
      per surgeon did not have a significant impact on flow efficiency. The use of
      specialized scrub nurses [-7.146 (3.099) min preparation time (p <= 0.05); -2.116
      (0.586) min turnover time (p <= 0.05)] and the eye clinic design [-1.742 (0.686)
      min exit time (p < 0.05); 2.296 (1.034) min turnover time (p <= 0.05)] benefit
      flow efficiency. CONCLUSION: Controllable and uncontrollable factors with
      clinical and organizational causes influencing flow efficiency in the cataract
      process were found. These factors can be taken into account in the management of
      the healthcare process.

PMID- 26310710
TI  - Sulforaphane inhibits damage-induced poly (ADP-ribosyl)ation via direct
      interaction of its cellular metabolites with PARP-1.
AB  - SCOPE: The isothiocyanate sulforaphane, a major breakdown product of the broccoli
      glucosinolate glucoraphanin, has frequently been proposed to exert
      anticarcinogenic properties. Potential underlying mechanisms include a zinc
      release from Kelch-like ECH-associated protein 1 followed by the induction of
      detoxifying enzymes. This suggests that sulforaphane may also interfere with
      other zinc-binding proteins, e.g. those essential for DNA repair. Therefore, we
      explored the impact of sulforaphane on poly (ADP-ribose)polymerase-1 (PARP-1),
      poly (ADP-ribosyl)ation (PARylation), and DNA single-strand break repair (SSBR)
      in cell culture. METHODS AND RESULTS: Immunofluorescence analyses showed that
      sulforaphane diminished H2 O2 -induced PARylation in HeLa S3 cells starting from
      15 MUM despite increased lesion induction under these conditions. Subcellular
      experiments quantifying the damage-induced incorporation of (32) P-ADP-ribose by
      PARP-1 displayed no direct impact of sulforaphane itself, but cellular
      metabolites, namely the glutathione conjugates of sulforaphane and its
      interconversion product erucin, reduced PARP-1 activity concentration
      dependently. Interestingly, this sulforaphane metabolite-induced PARP-1
      inhibition was prevented by thiol compounds. PARP-1 is a stimulating factor for
      DNA SSBR-rate and we further demonstrated that 25 MUM sulforaphane also delayed
      the rejoining of H2 O2 -induced DNA strand breaks, although this might be partly
      due to increased lesion frequencies. CONCLUSION: Sulforaphane interferes with
      damage-induced PARylation and SSBR, which implies a sulforaphane-dependent
      impairment of genomic stability.

PMID- 26310712
TI  - Formal total synthesis of (+)-cortistatins A and J.
AB  - An efficient formal total synthesis of (+) cortistatins A and J has been
      accomplished, by exploiting a highly diastereoselective intramolecular [4+3]
      cycloaddition of epoxy enolsilanes as the key reaction to construct rings B and C
      of the cortistatins in one step. 

PMID- 26310711
TI  - Effects of ADAM10 upregulation on progression, migration, and prognosis of
      nasopharyngeal carcinoma.
AB  - A disintegrin and metalloprotease 10 (ADAM10) is a typical member of the ADAMs
      family, which has been reported to be upregulated in various types of cancers and
      contribute to cancer progression and metastasis. However, little is known about
      the role of ADAM10 in nasopharyngeal carcinoma (NPC). The purpose of this study
      is to explore ADAM10 expression status and its biological functions in NPC. We
      first examined the expression of ADAM10 in NPC tissues and cell lines by
      immunohistochemistry, Western blotting, PCR, and immunofluorescence analysis. We
      observed that ADAM10 was significantly elevated in NPC and its expression level
      was correlated with T classification (P = 0.044), distant metastasis (P = 0.016),
      TNM clinical stage (P = 0.013), and proliferation marker Ki-67 expression (P =
      0.001). Patients with NPC with high expression of ADAM10 had shorter overall
      survival rates. In addition, knockdown of ADAM10 by RNAi was found to inhibit the
      CNE-2 cell proliferation and migration. Our findings hinted that overexpression
      of ADAM10 promotes the progression and migration of NPC, which makes it a
      potential therapeutic target for the treatment of tumor metastases in NPC. 

PMID- 26310713
TI  - Mechanistic model and analysis of doxorubicin release from liposomal
      formulations.
AB  - Reliable and predictive models of drug release kinetics in vitro and in vivo are
      still lacking for liposomal formulations. Developing robust, predictive release
      models requires systematic, quantitative characterization of these complex drug
      delivery systems with respect to the physicochemical properties governing the
      driving force for release. These models must also incorporate changes in release
      due to the dissolution media and methods employed to monitor release. This paper
      demonstrates the successful development and application of a mathematical
      mechanistic model capable of predicting doxorubicin (DXR) release kinetics from
      liposomal formulations resembling the FDA-approved nanoformulation DOXIL(r) using
      dynamic dialysis. The model accounts for DXR equilibria (e.g. self-association,
      precipitation, ionization), the change in intravesicular pH due to ammonia
      release, and dialysis membrane transport of DXR. The model was tested using a Box
      Behnken experimental design in which release conditions including extravesicular
      pH, ammonia concentration in the release medium, and the dilution of the
      formulation (i.e. suspension concentration) were varied. Mechanistic model
      predictions agreed with observed DXR release up to 19h. The predictions were
      similar to a computer fit of the release data using an empirical model often
      employed for analyzing data generated from this type of experimental design.
      Unlike the empirical model, the mechanistic model was also able to provide
      reasonable predictions of release outside the tested design space. These results
      illustrate the usefulness of mechanistic modeling to predict drug release from
      liposomal formulations in vitro and its potential for future development of in
      vitro - in vivo correlations for complex nanoformulations. 

PMID- 26310714
TI  - Gait velocity and walking distance to predict community walking after stroke.
AB  - Gait speed and walking distance were evaluated as predictors for levels of
      community walking after stroke. In this study, 103 stroke survivors were
      identified as limited (n = 67) or independent community walkers (n = 36). Ten
      meter and six min walk tests were used to measure gait speed and walking
      distance, respectively. The discriminative properties of gait speed and walking
      distance for community walking were investigated using receiver operating
      characteristic curves. Cut-off values of 0.87 m/s for community walking gait
      speed for walking distance had positive predictive values of 65% and 55%,
      respectively. The negative predictive value ranged from 89% for gait speed to 79%
      for walking distance. Gait speed and walking distance showed significant
      differences between limited and independent community walking. Gait speed was
      more significantly related to community walking than walking distance. The
      results of this study suggest that gait speed is a better predictor for community
      walking than walking distance in moderately affected post-stroke survivors. 

PMID- 26310715
TI  - Cytokine-induced killer cells as immunotherapy for solid tumors: current evidence
      and perspectives.
AB  - Cytokine-induced killer (CIK) cells are ex vivo expanded T lymphocytes endowed
      with potent MHC-independent antitumor activity. CIK cells are emerging as
      promising therapeutic approach in the field of cancer adoptive immunotherapy,
      with biologic features favoring their transferability into clinical applications.
      Aim of this review is to present the biologic characteristic of CIK cells,
      discussing the main preclinical findings and initial clinical applications in the
      field of solid tumors. 

PMID- 26310716
TI  - Japanese family with congenital factor VII deficiency.
AB  - Congenital factor VII (FVII) deficiency is a rare bleeding disorder with
      autosomal recessive inheritance. The present female patient was diagnosed with
      congenital FVII deficiency because of low hepaplastin test (HPT), although
      vitamin K was given. Heterozygous p.A191T mutation was detected in the peripheral
      blood, and the same mutation was also found in the mother and sister. To the best
      of our knowledge, this is the fourth reported case of p.A191T mutation of FVII in
      the literature and the first to be reported in Japan. FVII coagulation activity
      (FVII:C) in asymptomatic heterozygous carriers is mildly reduced. Therefore, some
      patients may not be accurately diagnosed with congenital FVII deficiency. In
      infants with low HPT without vitamin K deficiency, congenital FVII deficiency
      should be considered.

PMID- 26310717
TI  - Exploratory Research on Time- and Space-Resolved Spectroscopy and Chemistry.
AB  - Exploratory Research on Time- and Space-Resolved Spectroscopy and Chemistry. 

PMID- 26310718
TI  - Closing the gaps on the viral photosystem-I psaDCAB gene organization.
AB  - Marine photosynthesis is largely driven by cyanobacteria, namely Synechococcus
      and Prochlorococcus. Genes encoding for photosystem (PS) I and II reaction centre
      proteins are found in cyanophages and are believed to increase their fitness. Two
      viral PSI gene arrangements are known, psaJF->C->A->B->K->E->D and psaD->C->A->B.
      The shared genes between these gene cassettes and their encoded proteins are
      distinguished by %G + C and protein sequence respectively. The data on the psaD
      >C->A->B gene organization were reported from only two partial gene cassettes
      coming from Global Ocean Sampling stations in the Pacific and Indian oceans. Now
      we have extended our search to 370 marine stations from six metagenomic projects.
      Genes corresponding to both PSI gene arrangements were detected in the Pacific,
      Indian and Atlantic oceans, confined to a strip along the equator (30 degrees N
      and 30 degrees S). In addition, we found that the predicted structure of the
      viral PsaA protein from the psaD->C->A->B organization contains a lumenal loop
      conserved in PsaA proteins from Synechococcus, but is completely absent in viral
      PsaA proteins from the psaJF->C->A->B->K->E->D gene organization and most
      Prochlorococcus strains. This may indicate a co-evolutionary scenario where
      cyanophages containing either of these gene organizations infect cyanobacterial
      ecotypes biogeographically restricted to the 30 degrees N and 30 degrees S
      equatorial strip. 

PMID- 26310720
TI  - A New Fluorescent "Off-On" Sensor for Al(3+) Derived from L-alanine and
      Salicylaldehyde.
AB  - The condensation product of L-alanine and salicylaldehyde was synthesised and
      characterised which was found to be selective fluorescent "on" sensor for Al(3+)
      ion with the detection limit 10(-6) M. The sensor is free of interferences from
      metal ions - Na(+), K(+), Ca(2+), Mn(2+), Co(2+), Ni(2+), Cu(2+), Pb(2+), Cd(2+),
      Hg(2+) and Fe(3+). The Fluorescence and the UV/visible spectral data reveals a
      1:1 interaction between the sensor and Al(3+) ion with binding constant 10(4.5).
      The DFT and TDDFT calculations confirm the structures of the sensor and the
      sensor-Al(3+) complex. 

PMID- 26310719
TI  - Advances in molecular-based personalized non-small-cell lung cancer therapy:
      targeting epidermal growth factor receptor and mechanisms of resistance.
AB  - Molecularly targeted therapies, directed against the features of a given tumor,
      have allowed for a personalized approach to the treatment of advanced non-small
      cell lung cancer (NSCLC). The reversible epidermal growth factor receptor (EGFR)
      tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib had undergone turbulent
      clinical development until it was discovered that these agents have preferential
      activity in patients with NSCLC harboring activating EGFR mutations. Since then,
      a number of phase 3 clinical trials have collectively shown that EGFR-TKI
      monotherapy is more effective than combination chemotherapy as first-line therapy
      for EGFR mutation-positive advanced NSCLC. The next generation of EGFR-directed
      agents for EGFR mutation-positive advanced NSCLC is irreversible TKIs against
      EGFR and other ErbB family members, including afatinib, which was recently
      approved, and dacomitinib, which is currently being tested in phase 3 trials. As
      research efforts continue to explore the various proposed mechanisms of acquired
      resistance to EGFR-TKI therapy, agents that target signaling pathways downstream
      of EGFR are being studied in combination with EGFR TKIs in molecularly selected
      advanced NSCLC. Overall, the results of numerous ongoing phase 3 trials involving
      the EGFR TKIs will be instrumental in determining whether further gains in
      personalized therapy for advanced NSCLC are attainable with newer agents and
      combinations. This article reviews key clinical trial data for personalized NSCLC
      therapy with agents that target the EGFR and related pathways, specifically based
      on molecular characteristics of individual tumors, and mechanisms of resistance. 

PMID- 26310721
TI  - Pulp-dentin Regeneration: Current State and Future Prospects.
AB  - The goal of regenerative endodontics is to reinstate normal pulp function in
      necrotic and infected teeth that would result in reestablishment of protective
      functions, including innate pulp immunity, pulp repair through mineralization,
      and pulp sensibility. In the unique microenvironment of the dental pulp, the
      triad of tissue engineering would require infection control, biomaterials, and
      stem cells. Although revascularization is successful in resolving apical
      periodontitis, multiple studies suggest that it alone does not support pulp
      dentin regeneration. More recently, cell-based approaches in endodontic
      regeneration based on pulpal mesenchymal stem cells (MSCs) have demonstrated
      promising results in terms of pulp-dentin regeneration in vivo through autologous
      transplantation. Although pulpal regeneration requires the cell-based approach,
      several challenges in clinical translation must be overcome-including aging
      associated phenotypic changes in pulpal MSCs, availability of tissue sources, and
      safety and regulation involved with expansion of MSCs in laboratories.
      Allotransplantation of MSCs may alleviate some of these obstacles, although the
      long-term stability of MSCs and efficacy in pulp-dentin regeneration demand
      further investigation. For an alternative source of MSCs, our laboratory
      developed induced MSCs (iMSCs) from primary human keratinocytes through
      epithelial-mesenchymal transition by modulating the epithelial plasticity genes.
      Initially, we showed that overexpression of DeltaNp63alpha, a major isoform of
      the p63 gene, led to epithelial-mesenchymal transition and acquisition of stem
      characteristics. More recently, iMSCs were generated by transient knockdown of
      all p63 isoforms through siRNA, further simplifying the protocol and resolving
      the potential safety issues of viral vectors. These cells may be useful for
      patients who lack tissue sources for endogenous MSCs. Further research will
      elucidate the level of potency of these iMSCs and assess their
      transdifferentiation capacities into functional odontoblasts when transplanted
      into the root canal microenvironment. 

PMID- 26310722
TI  - Dental Occlusal Changes Induce Motor Cortex Neuroplasticity.
AB  - Modification to the dental occlusion may alter oral sensorimotor functions.
      Restorative treatments aim to restore sensorimotor functions; however, it is
      unclear why some patients fail to adapt to the restoration and remain with
      sensorimotor complaints. The face primary motor cortex (face-M1) is involved in
      the generation and control of orofacial movements. Altered sensory inputs or
      motor function can induce face-M1 neuroplasticity. We took advantage of the
      continuous eruption of the incisors in Sprague-Dawley rats and used intracortical
      microstimulation (ICMS) to map the jaw and tongue motor representations in face
      M1. Specifically, we tested the hypothesis that multiple trimming of the right
      mandibular incisor, to keep it out of occlusal contacts for 7 d, and subsequent
      incisor eruption and restoration of occlusal contacts, can alter the ICMS-defined
      features of jaw and tongue motor representations (i.e., neuroplasticity). On days
      1, 3, 5, and 7, the trim and trim-recovered groups had 1 to 2 mm of incisal
      trimming of the incisor; a sham trim group had buccal surface trimming with no
      occlusal changes; and a naive group had no treatment. Systematic mapping was
      performed on day 8 in the naive, trim, and sham trim groups and on day 14 in the
      trim-recovered group. In the trim group, the tongue onset latency was shorter in
      the left face-M1 than in the right face-M1 (P < .001). In the trim-recovered
      group, the number of tongue sites and jaw/tongue overlapping sites was greater in
      the left face-M1 than in the right face-M1 (P = 0.0032, 0.0016, respectively),
      and the center of gravity was deeper in the left than in the right face-M1 (P =
      0.026). Therefore, incisor trimming and subsequent restoration of occlusal
      contacts induced face-M1 neuroplasticity, reflected in significant disparities
      between the left and right face-M1 in some ICMS-defined features of the tongue
      motor representations. Such neuroplasticity may reflect or contribute to
      subjects' ability to adapt their oral sensorimotor functions to an altered dental
      occlusion. 

PMID- 26310723
TI  - Bone Aging by Advanced Glycation End Products: A Multiscale Mechanical Analysis.
AB  - The quality and quantity of mandibular bone are essential prerequisites for
      osseointegrated implants. Only the Hounsfield unit on preoperative computed
      tomography is currently used as a clinical index. Nevertheless, a considerable
      mismatch occurs between bone quality and the Hounsfield unit. Loss of bone
      toughness during aging has been accepted based on empirical evidence, but this
      concept is unlikely evidence based at the level of mechanical properties.
      Nonenzymatic bone matrix cross-links associated with advanced glycation end
      products predominate as a consequence of aging. Thus, loss of tissue integrity
      could diminish the bone toughening mechanism. Here, we demonstrate an impaired
      bone toughening mechanism caused by mimicking aging in rabbits on a methionine
      rich diet, which enabled an enhanced nonenzymatically cross-linked bone matrix. A
      3-point bending test revealed a greater reduction in femoral fracture resistance
      in rabbits on a methionine-rich diet, despite higher maximum and normalized
      breaking forces (287.3 N and 88.1%, respectively), than in rabbits on a normal
      diet (262.2 N and 79.7%, respectively). In situ nanoindentation on mandibular
      cortical bone obtained from rabbits on a methionine-rich diet did not enable
      strain rate-dependent stiffening and consequent large-dimensional recovery during
      rapid loading following constant displacement after a rapid-load indentation test
      as compared with those in rabbits on a normal diet. Such nanoscale structure
      function relationships dictate resistance to cracking propagation at the material
      level and allow for the overall bone toughening mechanism to operate under large
      external stressors. The strain-dependent stiffening was likely associated with
      strain-energy transfer to the superior cross-linked bone matrix network of the
      normal diet, while the reduction in the enzymatically cross-linked matrix in bone
      samples from rabbits on a methionine-rich diet likely diminished the intrinsic
      bone toughening mechanism. The present study also provides a precise protocol for
      evaluating bone mechanical properties at the material level based on observations
      from a series of nanoindentation experiments. 

PMID- 26310724
TI  - Discovery of gamma-Mangostin as an Amyloidogenesis Inhibitor.
AB  - Transthyretin (TTR) is a homotetrameric protein involved in human hereditary
      amyloidoses. The discovery and development of small molecules that inhibit the
      amyloid fibril formation of TTR is one of the therapeutic strategies for these
      diseases. Herein, we discovered that gamma-mangostin (gamma-M) is an effective
      inhibitor against the amyloid fibril formation of V30M amyloidogenic TTR. In
      vitro binding assays revealed that gamma-M was the most potent of the selected
      xanthone derivatives, and it bound to the thyroxine (T4)-binding sites and
      stabilized the TTR tetramer. X-ray crystallographic analysis revealed the
      diagonal binding mode of gamma-M and the two binding sites of chloride ions at
      the T4-binding site. One of the chloride ions was replaced with a water molecule
      in the alpha-mangostin complex, which is a methylated derivative of gamma-M. The
      stronger inhibitory potency of gamma-M could be explained by the additional
      hydrogen bonds with the chloride ion. The present study establishes gamma-M as a
      novel inhibitor of TTR fibrillization. 

PMID- 26310727
TI  - Expectations Among Academic Clinicians of Inpatient Imaging Turnaround Time: Does
      it Correlate with Satisfaction?
AB  - RATIONALE AND OBJECTIVES: Imaging report turnaround time (RTAT) is an important
      measure of radiology performance and has become the leading priority in customer
      satisfaction surveys conducted among nonradiologists, who may not be familiar
      with the imaging workflow. Our aim was to assess physicians' expected RTAT for
      commonly ordered studies and determine if satisfaction correlates with met
      expectations. MATERIALS AND METHODS: Retrospective review of inpatient imaging
      was conducted at a single academic institution, and RTAT for 18,414 studies was
      calculated. Examinations were grouped by study type, priority, and time of day. A
      cross-sectional survey instrument was completed by 48 internal medicine and
      surgery resident physicians with questions regarding RTAT and their level of
      satisfaction with various examinations. RESULTS: Actual RTAT ranged from 1.6 to
      26.0 hours, with chest radiographs and computed tomographies generally faster
      than magnetic resonance images and ultrasounds. Urgent (STAT) examinations and
      those ordered during business hours have shorter RTAT. The time for image
      interpretation largely contributed to the RTAT because of the lack of night-time
      radiology coverage. Referring physician expectations were consistently shorter
      than actual RTAT, ranging from 30 minutes to 24 hours. Overall satisfaction
      scores were inversely correlated with RTAT, with a strong correlation to the time
      from study order to imaging (r(2) = 0.63) and a weak correlation to the image
      interpretation time (r(2) = 0.17). Satisfaction scores did not correlate with
      whether the actual RTAT met expectations (r(2) = 0.06). CONCLUSIONS: Referring
      physician satisfaction is likely multifactorial. Although RTAT has been reported
      as a priority, shortening turnaround time alone may not directly improve
      clinician satisfaction.

PMID- 26310725
TI  - Epidemiology of Methicillin-Resistant Staphylococcus aureus Bloodstream
      Coinfection Among Adults With Candidemia in Atlanta, GA, 2008-2012.
AB  - BACKGROUND: Patients with candidemia are at risk for other invasive infections,
      such as methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection
      (BSI). OBJECTIVE: To identify the risk factors for, and outcomes of, BSI in
      adults with Candida spp. and MRSA at the same time or nearly the same time.
      DESIGN: Population-based cohort study. SETTING: Metropolitan Atlanta, March 1,
      2008, through November 30, 2012. PATIENTS: All residents with Candida spp. or
      MRSA isolated from blood. METHODS: The Georgia Emerging Infections Program
      conducts active, population-based surveillance for candidemia and invasive MRSA.
      Medical records for patients with incident candidemia were reviewed to identify
      cases of MRSA coinfection, defined as incident MRSA BSI 30 days before or after
      candidemia. Multivariate logistic regression was performed to identify factors
      associated with coinfection in patients with candidemia. RESULTS: Among 2,070
      adult candidemia cases, 110 (5.3%) had coinfection within 30 days. Among these
      110 coinfections, MRSA BSI usually preceded candidemia (60.9%; n=67) or occurred
      on the same day (20.0%; n=22). The incidence of coinfection per 100,000
      population decreased from 1.12 to 0.53 between 2009 and 2012, paralleling the
      decreased incidence of all MRSA BSIs and candidemia. Thirty-day mortality was
      similarly high between coinfection cases and candidemia alone (45.2% vs 36.0%,
      P=.10). Only nursing home residence (odds ratio, 1.72 [95% CI, 1.03-2.86])
      predicted coinfection. CONCLUSIONS: A small but important proportion of patients
      with candidemia have MRSA coinfection, suggesting that heightened awareness is
      warranted after 1 major BSI pathogen is identified. Nursing home residents should
      be targeted in BSI prevention efforts.

PMID- 26310729
TI  - Heroism in Syria.

PMID- 26310728
TI  - Microbial synthesis of Pd/Fe3O4, Au/Fe3O4 and PdAu/Fe3O4 nanocomposites for
      catalytic reduction of nitroaromatic compounds.
AB  - Magnetically recoverable noble metal nanoparticles are promising catalysts for
      chemical reactions. However, the chemical synthesis of these nanocatalysts
      generally causes environmental concern due to usage of toxic chemicals under
      extreme conditions. Here, Pd/Fe3O4, Au/Fe3O4 and PdAu/Fe3O4 nanocomposites are
      biosynthesized under ambient and physiological conditions by Shewanella
      oneidensis MR-1. Microbial cells firstly transform akaganeite into magnetite,
      which then serves as support for the further synthesis of Pd, Au and PdAu
      nanoparticles from respective precursor salts. Surface-bound cellular components
      and exopolysaccharides not only function as shape-directing agent to convert some
      Fe3O4 nanoparticles to nanorods, but also participate in the formation of PdAu
      alloy nanoparticles on magnetite. All these three kinds of magnetic
      nanocomposites can catalyze the reduction of 4-nitrophenol and some other
      nitroaromatic compounds by NaBH4. PdAu/Fe3O4 demonstrates higher catalytic
      activity than Pd/Fe3O4 and Au/Fe3O4. Moreover, the magnetic nanocomposites can be
      easily recovered through magnetic decantation after catalysis reaction.
      PdAu/Fe3O4 can be reused in at least eight successive cycles of 4-nitrophenol
      reduction. The biosynthesis approach presented here does not require harmful
      agents or rigorous conditions and thus provides facile and environmentally benign
      choice for the preparation of magnetic noble metal nanocatalysts. 

PMID- 26310730
TI  - FDA vulnerability revealed.

PMID- 26310731
TI  - We must build resilience into our communities.

PMID- 26310743
TI  - Hurricane Katrina's psychological scars revealed.

PMID- 26310744
TI  - North Pacific 'blob' stirs up fisheries management.

PMID- 26310745
TI  - Minnesota bog study turns up the heat on peat.

PMID- 26310746
TI  - Biohackers gear up for genome editing.

PMID- 26310747
TI  - Ecologists embrace their urban side.

PMID- 26310748
TI  - How cities can beat the heat.

PMID- 26310749
TI  - The growing global battle against blood-sucking ticks.

PMID- 26310750
TI  - Water and climate: Recognize anthropogenic drought.

PMID- 26310754
TI  - Neuroanatomy: Forgotten findings of brain lymphatics.

PMID- 26310755
TI  - Food production: Cut food waste to help feed world.

PMID- 26310756
TI  - Europe: Lifelong learning for all in biomedicine.

PMID- 26310757
TI  - Offsets: Conservation served by flexibility.

PMID- 26310758
TI  - History: Physicist's death changed war policy.

PMID- 26310759
TI  - Yoichiro Nambu (1921-2015).

PMID- 26310760
TI  - Materials science: Superlattice substitution.

PMID- 26310761
TI  - Particle physics: Positrons ride the wave.

PMID- 26310762
TI  - Photonics: A stable narrow-band X-ray laser.

PMID- 26310763
TI  - The disruption of multiplanet systems through resonance with a binary orbit.
AB  - Most exoplanetary systems in binary stars are of S-type, and consist of one or
      more planets orbiting a primary star with a wide binary stellar companion.
      Planetary eccentricities and mutual inclinations can be large, perhaps forced
      gravitationally by the binary companion. Earlier work on single planet systems
      appealed to the Kozai-Lidov instability wherein a sufficiently inclined binary
      orbit excites large-amplitude oscillations in the planet's eccentricity and
      inclination. The instability, however, can be quenched by many agents that induce
      fast orbital precession, including mutual gravitational forces in a multiplanet
      system. Here we report that orbital precession, which inhibits Kozai-Lidov
      cycling in a multiplanet system, can become fast enough to resonate with the
      orbital motion of a distant binary companion. Resonant binary forcing results in
      dramatic outcomes ranging from the excitation of large planetary eccentricities
      and mutual inclinations to total disruption. Processes such as planetary
      migration can bring an initially non-resonant system into resonance. As it does
      not require special physical or initial conditions, binary resonant driving is
      generic and may have altered the architecture of many multiplanet systems. It can
      also weaken the multiplanet occurrence rate in wide binaries, and affect planet
      formation in close binaries. 

PMID- 26310764
TI  - Multi-gigaelectronvolt acceleration of positrons in a self-loaded plasma
      wakefield.
AB  - Electrical breakdown sets a limit on the kinetic energy that particles in a
      conventional radio-frequency accelerator can reach. New accelerator concepts must
      be developed to achieve higher energies and to make future particle colliders
      more compact and affordable. The plasma wakefield accelerator (PWFA) embodies one
      such concept, in which the electric field of a plasma wake excited by a bunch of
      charged particles (such as electrons) is used to accelerate a trailing bunch of
      particles. To apply plasma acceleration to electron-positron colliders, it is
      imperative that both the electrons and their antimatter counterpart, the
      positrons, are efficiently accelerated at high fields using plasmas. Although
      substantial progress has recently been reported on high-field, high-efficiency
      acceleration of electrons in a PWFA powered by an electron bunch, such an
      electron-driven wake is unsuitable for the acceleration and focusing of a
      positron bunch. Here we demonstrate a new regime of PWFAs where particles in the
      front of a single positron bunch transfer their energy to a substantial number of
      those in the rear of the same bunch by exciting a wakefield in the plasma. In the
      process, the accelerating field is altered--'self-loaded'--so that about a
      billion positrons gain five gigaelectronvolts of energy with a narrow energy
      spread over a distance of just 1.3 metres. They extract about 30 per cent of the
      wake's energy and form a spectrally distinct bunch with a root-mean-square energy
      spread as low as 1.8 per cent. This ability to transfer energy efficiently from
      the front to the rear within a single positron bunch makes the PWFA scheme very
      attractive as an energy booster to an electron-positron collider.

PMID- 26310765
TI  - Atomic inner-shell laser at 1.5-angstrom wavelength pumped by an X-ray free
      electron laser.
AB  - Since the invention of the first lasers in the visible-light region, research has
      aimed to produce short-wavelength lasers that generate coherent X-rays; the
      shorter the wavelength, the better the imaging resolution of the laser and the
      shorter the pulse duration, leading to better temporal resolution in probe
      measurements. Recently, free-electron lasers based on self-amplified spontaneous
      emission have made it possible to generate a hard-X-ray laser (that is, the
      photon energy is of the order of ten kiloelectronvolts) in an angstrom-wavelength
      regime, enabling advances in fields from ultrafast X-ray spectrosopy to X-ray
      quantum optics. An atomic laser based on neon atoms and pumped by a soft-X-ray
      (that is, a photon energy of less than one kiloelectronvolt) free-electron laser
      has been achieved at a wavelength of 14 nanometres. Here, we use a copper target
      and report a hard-X-ray inner-shell atomic laser operating at a wavelength of 1.5
      angstroms. X-ray free-electron laser pulses with an intensity of about 10(19)
      watts per square centimetre tuned to the copper K-absorption edge produced
      sufficient population inversion to generate strong amplified spontaneous emission
      on the copper Kalpha lines. Furthermore, we operated the X-ray free-electron
      laser source in a two-colour mode, with one colour tuned for pumping and the
      other for the seed (starting) light for the laser. 

PMID- 26310766
TI  - Substitutional doping in nanocrystal superlattices.
AB  - Doping is a process in which atomic impurities are intentionally added to a host
      material to modify its properties. It has had a revolutionary impact in altering
      or introducing electronic, magnetic, luminescent, and catalytic properties for
      several applications, for example in semiconductors. Here we explore and
      demonstrate the extension of the concept of substitutional atomic doping to
      nanometre-scale crystal doping, in which one nanocrystal is used to replace
      another to form doped self-assembled superlattices. Towards this goal, we show
      that gold nanocrystals act as substitutional dopants in superlattices of cadmium
      selenide or lead selenide nanocrystals when the size of the gold nanocrystal is
      very close to that of the host. The gold nanocrystals occupy random positions in
      the superlattice and their density is readily and widely controllable, analogous
      to the case of atomic doping, but here through nanocrystal self-assembly. We also
      show that the electronic properties of the superlattices are highly tunable and
      strongly affected by the presence and density of the gold nanocrystal dopants.
      The conductivity of lead selenide films, for example, can be manipulated over at
      least six orders of magnitude by the addition of gold nanocrystals and is
      explained by a percolation model. As this process relies on the self-assembly of
      uniform nanocrystals, it can be generally applied to assemble a wide variety of
      nanocrystal-doped structures for electronic, optical, magnetic, and catalytic
      materials. 

PMID- 26310767
TI  - Western US intermountain seismicity caused by changes in upper mantle flow.
AB  - Understanding the causes of intraplate earthquakes is challenging, as it requires
      extending plate tectonic theory to the dynamics of continental deformation.
      Seismicity in the western United States away from the plate boundary is clustered
      along a meandering, north-south trending 'intermountain' belt. This zone
      coincides with a transition from thin, actively deforming to thicker, less
      tectonically active crust and lithosphere. Although such structural gradients
      have been invoked to explain seismicity localization, the underlying cause of
      seismicity remains unclear. Here we show results from improved mantle flow models
      that reveal a relationship between seismicity and the rate change of 'dynamic
      topography' (that is, vertical normal stress from mantle flow). The associated
      predictive skill is greater than that of any of the other forcings we examined.
      We suggest that active mantle flow is a major contributor to seismogenic
      intraplate deformation, while gravitational potential energy variations have a
      minor role. Seismicity localization should occur where convective changes in
      vertical normal stress are modulated by lithospheric strength heterogeneities.
      Our results on deformation processes appear consistent with findings from other
      mobile belts, and imply that mantle flow plays a significant and quantifiable
      part in shaping topography, tectonics, and seismic hazard within intraplate
      settings. 

PMID- 26310768
TI  - The DNA of a nation.

PMID- 26310770
TI  - Questioning evidence of group selection in spiders.

PMID- 26310771
TI  - Group selection versus group adaptation.

PMID- 26310772
TI  - Pruitt & Goodnight reply.

PMID- 26310773
TI  - Pheromone binding proteins enhance the sensitivity of olfactory receptors to sex
      pheromones in Chilo suppressalis.
AB  - Sexual communication in moths offers a simplified scenario to model and
      investigate insect sensory perception. Both PBPs (pheromone-binding proteins) and
      PRs (pheromone receptors) are involved in the detection of sex pheromones, but
      the interplay between them still remains largely unknown. In this study, we have
      measured the binding affinities of the four recombinant PBPs of Chilo
      suppressalis (CsupPBPs) to pheromone components and analogs and characterized the
      six PRs using the Xenopus oocytes expression system. Interestingly, when the
      responses of PRs were recorded in the presence of PBPs, we measured in several
      combinations a dramatic increase in signals as well as in sensitivity of such
      combined systems. Furthermore, the discrimination ability of appropriate
      combinations of PRs and PBPs was improved compared with the performance of PBPs
      or PRs alone. Besides further supporting a role of PBPs in the pheromone
      detection and discrimination, our data shows for the first time that appropriate
      combinations of PRs and PBPs improved the discrimination ability of PBPs or PRs
      alone. The variety of responses measured with different pairing of PBPs and PRs
      indicates the complexity of the olfaction system, which, even for the relatively
      simple task of detecting sex pheromones, utilises a highly sophisticated
      combinatorial approach. 

PMID- 26310774
TI  - Continuous and reversible tuning of the disorder-driven superconductor-insulator
      transition in bilayer graphene.
AB  - The influence of static disorder on a quantum phase transition (QPT) is a
      fundamental issue in condensed matter physics. As a prototypical example of a
      disorder-tuned QPT, the superconductor-insulator transition (SIT) has been
      investigated intensively over the past three decades, but as yet without a
      general consensus on its nature. A key element is good control of disorder. Here,
      we present an experimental study of the SIT based on precise in-situ tuning of
      disorder in dual-gated bilayer graphene proximity-coupled to two superconducting
      electrodes through electrical and reversible control of the band gap and the
      charge carrier density. In the presence of a static disorder potential, Andreev
      paired carriers formed close to the Fermi level in bilayer graphene constitute a
      randomly distributed network of proximity-induced superconducting puddles. The
      landscape of the network was easily tuned by electrical gating to induce
      percolative clusters at the onset of superconductivity. This is evidenced by
      scaling behavior consistent with the classical percolation in transport
      measurements. At lower temperatures, the solely electrical tuning of the disorder
      induced landscape enables us to observe, for the first time, a crossover from
      classical to quantum percolation in a single device, which elucidates how thermal
      dephasing engages in separating the two regimes. 

PMID- 26310775
TI  - Effects of 22 Novel CYP2D6 Variants Found in the Chinese Population on the
      Bufuralol and Dextromethorphan Metabolisms In Vitro.
AB  - Cytochrome P450 2D6 (CYP2D6) is a highly polymorphic enzyme that metabolizes a
      large number of therapeutic drugs. To date, more than 100 CYP2D6 allelic variants
      have been reported. Among these variants, we recently identified 22 novel
      variants in the Chinese population. The aim of this study was to functionally
      characterize the enzymatic activity of these variants in vitro. A baculovirus
      mediated expression system was used to express wild-type CYP2D6.1 and other
      variants (CYP2D6.2, CYP2D6.10 and 22 novel CYP2D6 variants) at high levels. Then,
      the insect microsomes containing expressed CYP2D6 proteins were incubated with
      bufuralol or dextromethorphan at 37 degrees C for 20 or 25 min., respectively.
      After termination, the metabolites were extracted and used for the detection with
      high-performance liquid chromatography. Among the 24 CYP2D6 variants tested, two
      variants (CYP2D6.92 and CYP2D6.96) were found to be catalytically inactive. The
      remaining 22 variants exhibited significantly decreased intrinsic clearance
      values for bufuralol 1'-hydroxylation and 20 variants showed significantly lower
      intrinsic clearance values for dextromethorphan O-demethylation than those of the
      wild-type CYP2D6.1. Our in vitro results suggest that most of the variants
      exhibit significantly reduced catalytic activities compared with the wild-type,
      and these data provide valuable information for personalized medicine in Chinese
      and other Asian populations.

PMID- 26310776
TI  - Daily Estimation of Ground-Level PM2.5 Concentrations over Beijing Using 3 km
      Resolution MODIS AOD.
AB  - Estimating exposures to PM2.5 within urban areas requires surface PM2.5
      concentrations at high temporal and spatial resolutions. We developed a mixed
      effects model to derive daily estimations of surface PM2.5 levels in Beijing,
      using the 3 km resolution satellite aerosol optical depth (AOD) calibrated daily
      by the newly available high-density surface measurements. The mixed effects model
      accounts for daily variations of AOD-PM2.5 relationships and shows good
      performance in model predictions (R(2) of 0.81-0.83) and cross-validations (R(2)
      of 0.75-0.79). Satellite derived population-weighted mean PM2.5 for Beijing was
      51.2 MUg/m(3) over the study period (Mar 2013 to Apr 2014), 46% higher than
      China's annual-mean PM2.5 standard of 35 MUg/m(3). We estimated that more than
      19.2 million people (98% of Beijing's population) are exposed to harmful level of
      long-term PM2.5 pollution. During 25% of the days with model data, the population
      weighted mean PM2.5 exceeded China's daily PM2.5 standard of 75 MUg/m(3).
      Predicted high-resolution daily PM2.5 maps are useful to identify pollution "hot
      spots" and estimate short- and long-term exposure. We further demonstrated that a
      good calibration of the satellite data requires a relatively large number of
      ground-level PM2.5 monitoring sites and more are still needed in Beijing. 

PMID- 26310777
TI  - Augmentation of ferulic acid-induced vasorelaxation with aging and its structure
      importance in thoracic aorta of spontaneously hypertensive rats.
AB  - Aging deteriorates vascular functions such as vascular reactivity and stiffness.
      Thus far, various reports suggest that bioactive compounds can improve vascular
      functions. However, few age-related studies of natural bioactive compounds are
      available. The present study attempted to evaluate age-related vasorelaxation of
      bioactive cinnamic acids, caffeic acid, and ferulic acid using aged rat thoracic
      aorta. Vasorelaxation was evaluated in thoracic aorta from both 8, 18, and 40
      weeks old Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR)
      respectively. The result indicated that caffeic acid possessed the vasorelaxation
      regardless of aging in WKY and SHR. Moreover, the vasorelaxation of ferulic acid
      enhanced with aging in SHR. The vasorelaxation behavior was acted in an
      endothelium-independent manner. To access structure importance of enhanced
      vasorelaxation, analogues of ferulic acid were tested. In 40 weeks old SHR, 3,4
      dimethoxycinnamic acid and coniferyl alcohol exhibited equivalent vasorelaxation
      activity with ferulic acid, providing the structural importance of methoxy
      modified 3-position on the phenyl ring and 2-propenoic moiety. These results
      firstly demonstrated that enhanced vasorelaxation of ferulic acid with aging and
      3,4-dimethoxycinnamic acid and coniferyl alcohol, along with ferulic acid, might
      exhibit the therapeutic potential of vasoactive power with aging. 

PMID- 26310778
TI  - Swim-up of tammar wallaby (Macropus eugenii) spermatozoa in Biggers, Whitter and
      Whittingham (BWW) medium: maximisation of sperm motility, minimisation of
      impairment of sperm metabolism and induction of sperm hyperactivation.
AB  - A variety of media were compared for their ability to sustain the motility of
      tammar wallaby spermatozoa over an 8-h period following swim-up from coagulated
      semen. The study demonstrated that a modified Tyrode's solution, Biggers, Whitter
      and Whittingham medium (BWW) was significantly better than any of the other
      assessed media in supporting wallaby sperm motility. After 8h of incubation in
      BWW, motility was maintained at 79.3+/-9.3%, with 77.0+/-10.4% rapid and 65.7+/
      8.7% progressively motile spermatozoa. By contrast, motility was <10% at the same
      8-h time point in all of the other media assessed. After 2h of incubation in BWW,
      tammar spermatozoa consumed more oxygen than their counterparts in PBS (52.0+/
      2.7 vs 75.0+/-6.6MUL per 108 spermatozoa per 2h; P<0.001). Motility was not
      enhanced in any of these media by the addition of 5mM N-acetyl-D-glucosamine, the
      major energy substrate in wallaby semen. However, addition of dibutyryl cAMP and
      pentoxifylline in BWW resulted in the extremely rapid induction of hyperactivated
      motility in the entire sperm population. This burst of hyperactivated motility
      was entirely dependent on calcium in BWW and significantly inhibited by
      calmidazolium, a calmodulin inhibitor. A set of computer-assisted sperm analysis
      parameters were identified that permitted the accurate quantification of
      hyperactivation rates in this species. This is the first comparative analysis of
      media for harvesting and incubating marsupial spermatozoa and the first record of
      hyperactivated motility in any marsupial species.

PMID- 26310780
TI  - Aenictushoelldobleri sp. n., a new species of the Aenictusceylonicus group
      (Hymenoptera, Formicidae) from China, with a key to the Chinese members of the
      group.
AB  - Aenictus is the most species-rich genus of army ants in the subfamily Dorylinae
      and one of the most species rich ant genera in China and the world. In this
      paper, a new species of the Aenictusceylonicus group, Aenictushoelldobleri sp.
      n., is described and illustrated based on the worker caste. The new species
      occurs in the subtropical forests of south-east China and is morphologically most
      similar to Aenictushenanensis Li & Wang, 2005 and Aenictuswudangshanensis Wang,
      2006. Aenictushoelldobleri sp. n. can be distinguished from both species by the
      shape of the subpetiolar process. The new species also resembles
      AenictuslifuiaeTerayama 1984 and Aenictusthailandianus Terayama & Kubota, 1993
      but clearly differs in various features of the cuticular sculpture. A key to the
      Chinese species of the Aenictusceylonicus group based on the worker caste is
      provided, which may help to reassess and clarify the taxonomic status of the
      abundant Chinese records of the true Aenictusceylonicus (Mayr, 1866), a species
      which almost certainly does not occur in China. Several new locality records are
      given, among them the first record of Aenictuswatanasiti Jaitrong & Yamane, 2013
      from China. 

PMID- 26310779
TI  - Shen-Kang protects 5/6 nephrectomized rats against renal injury by reducing
      oxidative stress through the MAPK signaling pathways.
AB  - Chronic kidney disease (CKD) is a worldwide public health concern with limited
      treatment options. The incidence of CDK is increasing and the disease is
      associated with a poor quality of life and a high financial cost of treatment.
      Shen-Kang (SK), a traditional Chinese herbal medicine, has been used clinically
      in the treatment of renal diseases for decades. This study was carried out to
      validate the therapeutic effects of SK on renal injury induced by 5/6
      nephrectomy, as well as its effects on the apoptosis of proximal tubule
      epithelial cells (HK-2 cells), in an aim to elucidate its mechanisms of action.
      For this purpose, an animal model of renal injury was created by subjecting rats
      to a 5/6 nephrectomy. The rats in the sham-operated and model groups received
      distilled water, while the rats in the SK and enalapril (EN) groups were treated
      with SK or EN. The levels of blood urea nitrogen (BUN) and serum creatinine (SCr)
      were measured. Kidney tissues obtained from the rats were stained with
      hematoxylin and eosin. HK-2 cells were employed to investigate the effects of SK
      on the apoptosis of renal proximal tubule epithelial cells induced by treatment
      with hydrogen peroxide (H2O2). In addition, cell viability was measured by MTT
      assay. Apoptotic events were monitored by western blot analysis, flow cytometric
      analysis and nuclear morphological anlaysis. The levels of intracellular reactive
      oxygen species (ROS) were measured by flow cytometric analysis with
      dihydroethidium staining. The results revealed that the administration of SK to
      5/6 nephrectomized rats for 1 week significantly decreased the levels of SCr and
      BUN. The morphological observations of the kidneys also indicated the
      amelioration of damage to renal tissue. Treatment of the HK-2 cells with SK
      significantly protected the cells from H2O2-induced apoptosis, as indicated by an
      increase in cell viability, the decrease in the cleavage of poly(ADP-ribose)
      polymerase (PARP) and fewer condensed nuclei. H2O2-induced ROS production was
      also attenuated by treatment with SK. Of note, the increase in the levels of
      phosphorylated extracellular signal-regulated kinase (ERK) and phosphorylated p38
      which occurred in response to exposure to H2O2 was inhibited by treatment with
      SK. No changes were observed in the levels of phosphorylated JNK under the same
      treatment conditions. Thus, the mitogen-activated protein kinase (MAPK) signaling
      pathways play an essential role in the development of CKD. SK alleviated renal
      injury in rats induced by 5/6 nephrectomy and prevented the H2O2-induced
      apoptosis of HK-2 cells through the MAPK signaling pathways. 

PMID- 26310781
TI  - Effect of Hemodialysis on 7-Year Clinical Outcomes After Sirolimus-Eluting Stent
      Implantation.
AB  - BACKGROUND: Hemodialysis (HD) patients are reported to show poor clinical
      outcomes after percutaneous coronary intervention (PCI) with sirolimus-eluting
      stent (SES) compared with non-HD patients and their long-term prognosis remains
      unclear. METHODS AND RESULTS: We prospectively enrolled 489 consecutive patients
      undergoing PCI with SES and performed a retrospective analysis focusing on HD
      patients. Median follow-up was 7.0 years (interquartile range, 4.2-7.9) and the
      follow-up rate was 100%. At the 7-year follow-up, the cumulative incidences of
      all-cause death, target lesion revascularization (TLR) and major adverse cardiac
      events (MACE) were significantly higher in HD patients than in non-HD patients
      (HD vs. non-HD=34.7% vs. 9.6%, 42.6% vs. 10.2% and 75.3% vs. 24.4%, respectively;
      log-rank P<0.001). Cox-proportional hazard analysis revealed that independent
      predictors of all-cause death were HD (hazard ratio [HR] 2.88, 95% confidence
      interval [CI]: 1.39-6.00), insulin-treated diabetes mellitus (HR 2.19, 95% CI:
      1.17-4.11), heart failure (HR 2.58, 95% CI: 1.25-5.32) and older age (HR 1.06/1
      age, 95% CI: 1.02-1.10). Moreover, HD was an independent predictor of TLR (HR
      3.63, 95% CI: 1.85-7.11) and MACE (HR 3.54, 95% CI: 2.19-5.73). CONCLUSIONS: In
      the present study, Japanese HD patients undergoing PCI with SES showed poorer
      long-term clinical outcomes than non-HD patients. HD was a strong predictor of
      long-term adverse events after SES implantation.

PMID- 26310782
TI  - Impact of novel balloon catheter on static balloon atrial septostomy with double
      balloon technique in infants with congenital heart disease.
AB  - BACKGROUND: The aim of this study was to investigate the feasibility of static
      balloon atrial septostomy (BAS) with the double balloon technique for infants.
      TMP PED balloon catheter, newly designed for static BAS in small children, was
      used in 3 infants. The balloon catheter has a low profile, short and round
      shoulder, and smooth deflation without slippage. METHODS AND RESULTS: Three
      infants (transposition of the great arteries, n=2; pulmonary atresia with intact
      ventricular septum, n=1) underwent static BAS with double balloon for restrictive
      interatrial communication between December 2014 and March 2015. Hemodynamic and
      echocardiographic assessment was done before and after the procedure. Pressure
      gradient between left and right atrium decreased from 6, 7 and 9 mmHg to 2, 2 and
      1 mmHg, respectively. Oxygen saturation in systemic artery increased from 72, 68
      and 73% to 78, 70 and 79%, respectively. Maximum defect diameter increased from
      3.5, 3.0 and 3.3 mm to 6.6*5.2, 9.0*6.2 and 8.1*5.1 mm, respectively. No
      complication was recorded. CONCLUSIONS: Static BAS with double balloon technique
      using the novel TMP PED balloon catheter was safe and effective in producing
      sufficient interatrial communication for 8-20 weeks in infants. Static BAS is a
      promising procedure to create interatrial communication in infants.

PMID- 26310783
TI  - Coronary Imaging Modalities for Forecasting the "Eruption of the Volcano".

PMID- 26310785
TI  - Dicobalt phosphide nanoparticles encased in boron and nitrogen co-doped graphitic
      layers as novel non-precious metal oxygen reduction electrocatalysts in alkaline
      media.
AB  - Dicobalt phosphide nanoparticles encased in boron and nitrogen co-doped graphitic
      layers (BNC/Co2P) were fabricated using a one-step pyrolysis method, which
      exhibited outstanding electrocatalytic ORR performance comparable to commercial
      Pt/C towards the oxygen reduction reaction via a four-electron pathway in
      alkaline solution with long-term stability and excellent methanol tolerance. 

PMID- 26310784
TI  - Whole-body vibration-induced muscular reflex: Is it a stretch-induced reflex?
AB  - [Purpose] Whole-body vibration (WBV) can induce reflex responses in muscles. A
      number of studies have reported that the physiological mechanisms underlying this
      type of reflex activity can be explained by reference to a stretch-induced
      reflex. Thus, the primary objective of this study was to test whether the WBV
      induced muscular reflex (WBV-IMR) can be explained as a stretch-induced reflex.
      [Subjects and Methods] The present study assessed 20 healthy males using surface
      electrodes placed on their right soleus muscle. The latency of the tendon reflex
      (T-reflex) as a stretch-induced reflex was compared with the reflex latency of
      the WBV-IMR. In addition, simulations were performed at 25, 30, 35, 40, 45, and
      50 Hz to determine the stretch frequency of the muscle during WBV. [Results] WBV
      IMR latency (40.5 +/- 0.8 ms; 95% confidence interval [CI]: 39.0-41.9 ms) was
      significantly longer than T-reflex latency (34.6 +/- 0.5 ms; 95% CI: 33.6-35.5
      ms) and the mean difference was 6.2 ms (95% CI of the difference: 4.7-7.7 ms).
      The simulations performed in the present study demonstrated that the frequency of
      the stretch signal would be twice the frequency of the vibration. [Conclusion]
      These findings do not support the notion that WBV-IMR can be explained by
      reference to a stretch-induced reflex. 

PMID- 26310786
TI  - Tectonic-1 contributes to the growth and migration of prostate cancer cells in
      vitro.
AB  - Tectonic-1 (TCTN1) is an upstream gene involved in embryonic development. The aim
      of the present study was to investigate the effect of the TCTN1 gene on the
      viability and migration of prostate cancer cells. Lentivirus-mediated short
      hairpin RNA (shRNA) was constructed to silence the expression of TCTN1 in PC-3
      and DU145 prostate cancer cells. Cell viability and proliferation were measured
      using MTT and colony formation assays, and the distribution of cells in phases of
      the cell cycle was determined using flow cytometry. Cell migration was detected
      using a Transwell assay. The results demonstrated that TCTN1 was widely expressed
      in several human prostate cancer cell lines. Knockdown of the TCTN1 gene by RNA
      interference markedly suppressed cell viability and colony formation in the PC-3
      and DU145 cell lines. Cell cycle progression was also arrested by TCTN1
      silencing. In addition, knockdown of the TCTN1 gene led to the inhibition of cell
      migration in the two cell lines. These findings confirmed the direct association
      between the TCTN1 gene and prostate cancer growth in vitro. With further
      understanding and clinical investigation, this indicates the potential for future
      development of a novel marker for early detection and gene therapy for prostate
      cancer. 

PMID- 26310787
TI  - Dutch family physicians' awareness of cognitive impairment among the elderly.
AB  - BACKGROUND: Dementia is often not formally diagnosed in primary care. To what
      extent this is due to family physicians' (FPs) watchful waiting, reluctance to
      diagnose or to their unawareness of the presence of cognitive impairment is
      unclear. The objective of this study was to assess FPs' awareness of cognitive
      impairment by comparing their evaluation of the absence or presence of cognitive
      impairment in older patients without an established diagnosis of dementia, with a
      reference test of cognitive functioning. In addition, we assessed which patient
      characteristics were associated with con- and discordance between FPs' evaluation
      of cognition and results of the reference test. METHODS: The design was a nested
      diagnostic study. FPs (n = 29) of 15 primary care practices classified the
      cognitive status of all their patients >= 65 years of age (n = 7865) into four
      categories, based on recollection and medical records. All patients categorized
      as 'possible cognitive impairment or dementia' and a sample of patients
      categorized as 'no signs of cognitive impairment' randomly selected to match age
      and gender were offered to receive a reference test of cognitive function (the
      CAMCOG) to verify the FPs' label. This reference test could yield three outcomes:
      no cognitive impairment, amnestic mild cognitive impairment (aMCI) or dementia.
      Reference test results were weighted back to the original samples to provide
      estimates for the correct categorization of elderly as 'possible cognitive
      impairment or dementia' (positive predictive value [PPV]) and 'no signs of
      cognitive impairment' (negative predictive value [NPV]). Cognitive functioning
      was not assessed for patients evaluated by FPs as 'probable dementia' and
      'unknown or no recent contact'. Characteristics associated with the con- or
      discordance of the FPs' classification and the reference test were assessed using
      logistic regression. RESULTS: Complete reference test results were obtained from
      318 elderly. FPs labeled 8.3 % of elderly 'possible cognitive impairment or
      dementia'. The PPV of this label for a CAMCOG score suggestive of dementia or
      aMCI was 47.1 % (95 %-confidence interval: 43.5 - 62.4 %). FPs labeled 83.7 % 'no
      signs of cognitive impairment'. The 1-NPV of this label for a CAMCOG score
      suggestive of dementia or aMCI was 12.5 % (95 %-CI 8.2 - 16.8 %). FPs labeled 3.6
      % as 'probable dementia' and 4.5 % as 'unknown or no recent contact'. The odds
      that FPs' suspicion of cognitive impairment were confirmed by the CAMCOG were
      higher if persons were ADL dependent (OR 2.24 [95 %-CI 1.16 - 4.35]). The odds of
      FPs being unaware of the presence of cognitive impairment were higher in the
      older elderly (OR 1.15 [95 %-CI 1.09 - 1.23] per year). CONCLUSION: Evaluation of
      FPs' classification of the global cognitive function of elderly without a firm
      diagnosis of dementia showed both over- and unawareness of the presence of
      cognitive impairment. FPs were more often unaware of cognitive impairment in the
      older elderly.

PMID- 26310788
TI  - Do holes in long-lasting insecticidal nets compromise their efficacy against
      pyrethroid resistant Anopheles gambiae and Culex quinquefasciatus? Results from a
      release-recapture study in experimental huts.
AB  - BACKGROUND: Resistance of malaria vectors to pyrethroids threatens the
      effectiveness of long-lasting insecticidal nets (LLINs) as a tool for malaria
      control. Recent experimental hut and observational studies in Benin show that
      pyrethroid resistance reduces the insecticidal effect and personal protection of
      LLINs especially when they become torn. The World Health Organization has
      proposed a threshold for when nets are "too torn" at 1,000 cm(2) for rectangular
      holes and 790 cm(2) for round holes. This study examines whether there is a
      threshold above which LLINs no longer reduce malaria transmission. METHODS:
      Intact and artificially-holed LLINs under three months old and untreated nets
      were tested by releasing mosquitoes from a susceptible Anopheles gambiae colony,
      a pyrethroid-resistant An. gambiae population and a resistant Culex
      quinquefasciatus population in closed experimental huts in Southern Benin, West
      Africa. The efficacy of LLINs and untreated nets was evaluated in terms of
      protection against blood feeding, insecticidal effect and potential effect on
      malaria transmission. RESULTS: Personal protection by both LLINs and untreated
      nets decreased exponentially with increasing holed surface area, without evidence
      for a specific threshold beyond which LLINs could be considered as ineffective.
      The insecticidal effect of LLINs was lower in resistant mosquitoes than in
      susceptible mosquitoes, but holed surface area had little or no impact on the
      insecticidal effect of LLINs. LLINs with 22,500 cm(2) holed surface area and
      target insecticide content provided a personal protection of 0.60 (95 % CI 0.44
      0.73) and a low insecticidal effect of 0.20 (95 % CI 0.12-0.30) against resistant
      An. gambiae. Nevertheless, mathematical models suggested that if 80 % of the
      population uses such nets, they could still prevent 94 % (95 % CI 89-97 %) of
      transmission by pyrethroid-resistant An. gambiae. CONCLUSIONS: Even though
      personal protection by LLINs against feeding mosquitoes is strongly reduced by
      holes, the insecticidal effect of LLINs is independent of the holed surface area,
      but strongly dependent on insecticide resistance. Badly torn nets that still
      contain insecticide have potential to reduce malaria transmission. The
      relationship between LLIN integrity and efficacy needs to be understood in order
      to guide LLIN distribution policy.

PMID- 26310789
TI  - How do species, population and active ingredient influence insecticide
      susceptibility in Culicoides biting midges (Diptera: Ceratopogonidae) of
      veterinary importance?
AB  - BACKGROUND: Culicoides biting midges are biological vectors of internationally
      important arboviruses of livestock and equines. Insecticides are often employed
      against Culicoides as a part of vector control measures, but systematic
      assessments of their efficacy have rarely been attempted. The objective of the
      present study is to determine baseline susceptibility of multiple Culicoides
      vector species and populations in Europe and Africa to the most commonly used
      insecticide active ingredients. Six active ingredients are tested: three that are
      based on synthetic pyrethroids (alpha-cypermethrin, deltamethrin and permethrin)
      and three on organophosphates (phoxim, diazinon and chlorpyrifos-methyl).
      METHODS: Susceptibility tests were conducted on 29,064 field-collected
      individuals of Culicoides obsoletus Meigen, Culicoides imicola Kieffer and a
      laboratory-reared Culicoides nubeculosus Meigen strain using a modified World
      Health Organization assay. Populations of Culicoides were tested from seven
      locations in four different countries (France, Spain, Senegal and South Africa)
      and at least four concentrations of laboratory grade active ingredients were
      assessed for each population. RESULTS: The study revealed that insecticide
      susceptibility varied at both a species and population level, but that broad
      conclusions could be drawn regarding the efficacy of active ingredients.
      Synthetic pyrethroid insecticides were found to inflict greater mortality than
      organophosphate active ingredients and the colony strain of C. nubeculosus was
      significantly more susceptible than field populations. Among the synthetic
      pyrethroids, deltamethrin was found to be the most toxic active ingredient for
      all species and populations. CONCLUSIONS: The data presented represent the first
      parallel and systematic assessment of Culicoides insecticide susceptibility
      across several countries. As such, they are an important baseline reference to
      monitor the susceptibility status of Culicoides to current insecticides and also
      to assess the toxicity of new active ingredients with practical implications for
      vector control strategies.

PMID- 26310791
TI  - Interface engineering for ternary blend polymer solar cells with a
      heterostructured near-IR dye.
AB  - Ternary-blend polymer solar cells can be effectively improved by incorporating a
      heterostructured near-IR dye, which has a hexyl group compatible with the polymer
      and a benzyl group compatible with the fullerene. Because of the compatibility
      with both materials, the heterostructured dye can be loaded up to 15 wt% and
      hence can boost the photocurrent generation by 30%. 

PMID- 26310790
TI  - Increased myocardial extracellular volume in active idiopathic systemic capillary
      leak syndrome.
AB  - BACKGROUND: The Systemic Capillary Leak Syndrome (SCLS) is a rare disorder of
      unknown etiology presenting as recurrent episodes of shock and peripheral edema
      due to leakage of fluid into soft tissues. Insights into SCLS pathogenesis are
      few due to the scarcity of cases, and the etiology of vascular barrier disruption
      in SCLS is unknown. Recent advances in cardiovascular magnetic resonance (CMR)
      allow for the quantitative assessment of the myocardial extracellular volume
      (ECV), which can be increased in conditions causing myocardial edema. We
      hypothesized that measurement of myocardial ECV may detect myocardial vascular
      leak in patients with SCLS. METHODS: Fifty-six subjects underwent a standard CMR
      examination at the NIH Clinical Center from 2009 until 2014: 20 patients with
      acute intermittent SCLS, six subjects with chronic SCLS, and 30 unaffected
      controls. Standard volumetric measurements; late gadolinium enhancement imaging
      and pre- and post-contrast T1 mapping were performed. ECV was calculated by
      calibration of pre- and post-contrast T1 values with blood hematocrit. RESULTS:
      Demographics and cardiac parameters were similar in both groups. There was no
      significant valvular disorder in either group. Subjects with chronic SCLS had
      higher pre-contrast myocardial T1 compared to healthy controls (T1: 1027 +/- 44
      v. 971 +/- 41, respectively; p = 0.03) and higher myocardial ECV than patients
      with acute intermittent SCLS or controls: 33.8 +/- 4.6, 26.9 +/- 2.6, 26 +/- 2.4,
      respectively; p = 0.007 v. acute intermittent; P = 0.0005 v. controls). When
      patients with chronic disease were analyzed together with five patients with
      acute intermittent disease who had just experienced an acute SCLS flare, ECV
      values were significantly higher than in subjects with acute intermittent SCLS in
      remission or age-matched controls and (31.2 +/- 4.6 %, 26.5 +/- 2.7 %, 26 +/- 2.4
      %, respectively; p = 0.01 v. remission, p = 0.001 v. controls). By contrast, T1
      values did not distinguish these three subgroups (1008 +/- 40, 978 +/- 40, 971 +/
      41, respectively, p = 0.2, active v. remission; p = 0.06 active v. controls).
      Abundant myocardial edema without evidence of acute inflammation was detected in
      cardiac tissue postmortem in one patient. CONCLUSIONS: Patients with active SCLS
      have significantly higher myocardial ECV than age-matched controls or SCLS
      patients in remission, which correlated with histopathological findings in one
      patient.

PMID- 26310792
TI  - Selection and characterization of novel DNA aptamers specifically recognized by
      Singapore grouper iridovirus-infected fish cells.
AB  - Singapore grouper iridovirus (SGIV) is a major viral pathogen of grouper
      aquaculture, and has caused heavy economic losses in China and South-east Asia.
      In this study, we generated four ssDNA aptamers against SGIV-infected grouper
      spleen (GS) cells using SELEX (systematic evolution of ligands by exponential
      enrichment) technology. Four aptamers exhibited high affinity to SGIV-infected GS
      cells, in particular the Q2 aptamer. Q2 had a binding affinity of 12.09 nM, the
      highest of the four aptamers. These aptamers also recognized SGIV-infected
      tissues with high levels of specificity. Protease treatment and flow cytometry
      analysis of SGIV-infected cells revealed that the target molecules of the Q3, Q4
      and Q5 aptamers were trypsin-sensitive proteins, whilst the target molecules of
      Q2 might be membrane lipids or surface proteins that were not trypsin-sensitive.
      The generated aptamers appeared to inhibit SGIV infection in vitro. Aptamer Q2
      conferred the highest levels of protection against SGIV and was able to inhibit
      SGIV infection in a dose-dependent manner. In addition, Q2 was efficiently
      internalized by SGIV-infected GS cells and localized at the viral assembly sites.
      Our results demonstrated that the four novel aptamers we generated were specific
      for SGIV-infected cells and could potentially be applied as rapid molecular
      diagnostic test reagents or therapeutic drugs targeting SGIV. 

PMID- 26310794
TI  - Are we there yet?

PMID- 26310793
TI  - Disparities in cardiovascular disease among Caribbean populations: a systematic
      literature review.
AB  - BACKGROUND: Cardiovascular diseases (CVD) are the predominant cause of death
      globally. The large health disparities in the distribution of the burden of
      disease seen in developed and developing countries are of growing concern.
      Central to this concern is the poor outcome which is seen disproportionately in
      socially disadvantaged groups and racial/ethnic minorities. The aim of the study
      was to conduct a systematic literature review to investigate the nature of
      cardiovascular disease health disparities among Afro-Caribbean origin populations
      and identify current knowledge gaps. METHODS: A systematic literature review
      including a detailed search strategy was developed to search MEDLINE and other
      research databases. Using an a priori protocol peer-reviewed publications and
      grey literature articles were retrieved and screened and relevant data extracted
      by two independent review authors. Thematic analysis was done according to CVD
      outcomes and measures of disparity including age, sex, ethnicity and
      socioeconomic status. RESULTS: The search retrieved 665 articles of which 22 met
      the inclusion criteria. Most studies were conducted in the United Kingdom and
      centered on the prevalence of CVD by ethnicity, age and sex. An important sub
      theme identified was the disparities in health service utilization/hospital
      admission. Coronary Heart Disease (CHD) and Peripheral Arterial Disease (PAD)
      were less prevalent among Afro-Caribbeans compared to Caucasian and South East
      Asian ethnic groups. The prevalence of CHD ranged from 0-7% in Afro-Caribbean to
      2-22% in Caucasians. Strokes were more common among Afro-Caribbeans. There are
      inadequate data on morbidity and mortality from CVD, particularly across the
      socio-economic gradient, in Afro-Caribbean populations. CONCLUSIONS: There are
      important differences in morbidity and mortality from CVD across ethnic groups.
      Important knowledge gaps remain in understanding the social determinants of these
      disparities in CVD. More research exploring these gaps by varying disparity
      indicators needs to be undertaken.

PMID- 26310795
TI  - Depolarising bipolarity: Clinical considerations.

PMID- 26310796
TI  - The mixed features of DSM-5.

PMID- 26310798
TI  - Enantioselective Synthesis of Various Cyanohydrins Using Covalently Immobilized
      Preparations of Hydroxynitrile Lyase from Prunus dulcis.
AB  - The carrier-based and carrier-free (cross-linked enzyme aggregate) covalent
      immobilizations of Prunus dulcis hydroxynitrile lyase were investigated. The
      immobilized preparations were tested for enantioselective carbon-carbon bond
      formation activity in the biphasic medium. Of the tested preparations, only cross
      linked enzyme aggregate of P. dulcis hydroxynitrile lyase (PdHNL-CLEA) achieved
      the synthesis of (R)-mandelonitrile with 93% yield and 99% enantiopurity. PdHNL
      CLEA was also used in the synthesis of various (R)-cyanohydrins from
      corresponding aldehydes/ketones and hydrocyanic acid. When 4-methoxybenzaldehyde,
      4-methyl benzaldehyde, and 4-hydroxybenzaldehyde were used as substrates, the
      yield-enantiomeric excess of corresponding (R)-cyanohydrins were obtained as 95
      95, 85-79, and 2-25%, respectively, after 96 h at pH 4.0 and 5  degrees C. For
      acetophenone, 4-fluoroacetophenone, 4-chloroacetophenone, 4-bromoacetophenone,
      and 4-iodoacetophenone, the yield-enantiomeric excess of corresponding (R)
      cyanohydrins were 1-99, 20-84, 11-95, 5-99, and 3-24%, respectively at the same
      conditions. The results demonstrate PdHNL-CLEA can be effectively used in the
      synthesis of (R)-mandelonitrile.

PMID- 26310799
TI  - Driver behavior following an automatic steering intervention.
AB  - The study investigated driver behavior toward an automatic steering intervention
      of a collision mitigation system. Forty participants were tested in a driving
      simulator and confronted with an inevitable collision. They performed a naive
      drive and afterwards a repeated exposure in which they were told to hold the
      steering wheel loosely. In a third drive they experienced a false alarm
      situation. Data on driving behavior, i.e. steering and braking behavior as well
      as subjective data was assessed in the scenarios. Results showed that most
      participants held on to the steering wheel strongly or counter-steered during the
      system intervention during the first encounter. Moreover, subjective data
      collected after the first drive showed that the majority of drivers was not aware
      of the system intervention. Data from the repeated drive in which participants
      were instructed to hold the steering wheel loosely, led to significantly more
      participants holding the steering wheel loosely and thus complying with the
      instruction. This study seems to imply that without knowledge and information of
      the system about an upcoming intervention, the most prevalent driving behavior is
      a strong reaction with the steering wheel similar to an automatic steering reflex
      which decreases the system's effectiveness. Results of the second drive show some
      potential for countermeasures, such as informing drivers shortly before a system
      intervention in order to prevent inhibiting reactions. 

PMID- 26310797
TI  - Fistula tract curettage and the use of biological dermal plugs improve high
      transsphincteric fistula healing in an animal model.
AB  - PURPOSE: The treatment of high transsphincteric fistula is a complex procedure,
      which may be associated with the risk of recurrence and fecal incontinence. In
      this study, we used an animal model to compare different types of sphincter
      preserving treatments for transsphincteric fistula. METHODS: Sixteen female New
      Zealand rabbits, weighing 2.8-4.8 kg underwent a surgical creation of high
      transsphincteric fistula. After 6 weeks, magnetic resonance imaging (MRI) was
      performed in order to confirm fistula formation and measure the fistula diameter.
      The rabbits were divided into three groups. Group 1 received no plug treatment
      (control). Autologous dermal graft and acellular dermal matrix were used as a
      plug in groups 2 and 3, respectively. Five weeks after treatment, fistula tract
      healing was determined by measuring the largest fistula diameter with MRI. All
      rabbits were euthanized and the anorectum excised en bloc for histopathological
      examination. RESULTS: According to the MRI findings, all groups showed
      significant healing after the treatment (p < 0.05). The healing rate of fistula
      diameters after treatment was 40, 66, and 29% in the control, dermal graft, and
      acellular dermal matrix groups, respectively. In terms of negative healing
      parameters such as neutrophil, eosinophil, lymphocyte, and plasmocyte
      accumulation, dermal graft and acellular dermal matrix groups showed
      significantly lower results than those in the control group (p < 0.05).
      CONCLUSION: According to MRI and histopathological results, fistula tract
      curettage and fistula orifice closure improved transsphincteric anal fistula
      healing. Additionally, in this study, plug treatment favoring autologous dermal
      graft resulted in better healing.

PMID- 26310800
TI  - Determining the effective location of a portable changeable message sign on
      reducing the risk of truck-related crashes in work zones.
AB  - Truck-related crashes contribute to a significant percentage of vehicle crashes
      in the United States, which often result in injuries and fatalities. The amount
      of truck miles traveled has increased dramatically with the growing rate of
      freight movement. Regarding truck crashes in the highway work zones, many studies
      indicated that there was a significant increase in crash severity when a truck
      crash occurred in work zones. To mitigate the risk of truck crashes in work
      zones, a portable changeable message sign (PCMS) was frequently utilized in
      addition to standard temporary traffic control signs and devices required by the
      Manual on Uniform Traffic Control Devices. To justify the use of a PCMS in work
      zones, there is a need to study the effective location of a PCMS deployed in a
      work zone by measuring the changes of truck and passenger car speed profiles. The
      difference of speed changes between trucks and passenger cars was considered as
      one of the major reasons which caused truck-related crashes in work zones.
      Therefore, reducing the difference of speed changes between trucks and passenger
      cars could potentially improve safety in work zones. The outcomes of this study
      will provide required knowledge for traffic engineers to effectively utilize the
      PCMS in work zones with the purpose of reducing truck-related crashes. In
      addition, the success of this study will provide a roadmap to investigate the
      effective deployment of other temporary traffic control devices on mitigating the
      risk of truck-related crashes in work zones. 

PMID- 26310801
TI  - A quantitative approach to assessing the efficacy of occupant protection
      programs: A case study from Montana.
AB  - Quantitative evaluation of vehicle occupant protection programs is critical for
      ensuring efficient government resource allocation, but few methods exist for
      conducting evaluation across multiple programs simultaneously. Here we present an
      analysis of occupant protection efficacy in the state of Montana. This approach
      relies on seat belt compliance rates as measured by the National Occupant
      Protection Usage Survey (NOPUS). A hierarchical logistic regression model is used
      to estimate the impacts of four Montana Department of Transportation (MDT)-funded
      occupant protection programs used in the state of Montana, following adjustment
      for a suite of potential confounders. Activity from two programs, Buckle Up
      coalitions and media campaigns, are associated with increased seat belt use in
      Montana, whereas the impact of another program, Selective Traffic Enforcement, is
      potentially masked by other program activity. A final program, Driver's
      Education, is not associated with any shift in seat belt use. This method allows
      for a preliminary quantitative estimation of program impacts without requiring
      states to obtain any new seat belt use data. This approach provides states a
      preliminary look at program impacts, and a means for carefully planning future
      program allocation and investigation. 

PMID- 26310802
TI  - New WHO recommendations to improve the outcomes of preterm birth.

PMID- 26310803
TI  - Chest compression duration influences outcome between integrated load
      distributing band and manual CPR during cardiac arrest.
AB  - BACKGROUND: The Circulation Improving Resuscitation Care (CIRC) Trial found
      equivalent survival in adult out-of-hospital cardiac arrest (OHCA) patients who
      received integrated load-distributing band CPR (iA-CPR) compared to manual CPR (M
      CPR). We hypothesized that as chest compression duration increased, iA-CPR
      provided a survival benefit when compared to M-CPR. METHODS: A pre-planned
      secondary analysis of OHCA of presumed cardiac etiology from the randomized CIRC
      trial. Chest compressions duration was defined as the total number of minutes
      spent on compressions during resuscitation and identified from transthoracic
      impedance and accelerometer data recorded by the EMS defibrillator. Logistic
      regression was used to model the interaction between treatment and duration of
      chest compressions and was covariate-adjusted for trial site, patient age,
      witnessed arrest, and initial shockable rhythm. Primary outcome was survival to
      hospital discharge. RESULTS: We enrolled 4231 subjects and of those, 2012 iA-CPR
      and 2002 M-CPR had complete outcome and duration of chest compressions data.
      While covariate-adjusted odds ratio for survival to hospital discharge was 1.86
      in favor of iA-CPR (95% CI 1.16-3.0), there was an interaction between duration
      and study arm. When this was factored into the multivariate equation, the odds
      ratio for survival to hospital discharge showed a significant benefit for iA-CPR
      vs. M-CPR for chest compression duration greater than 16.5 min. CONCLUSION: After
      adjusting for compression duration and duration-treatment interaction, iA-CPR
      showed a significant benefit for survival to hospital discharge vs. M-CPR in
      patients with OHCA if chest compression duration was longer than 16.5 min.

PMID- 26310804
TI  - Comparative Analysis and Functional Characterization of HC-AFW1 Hepatocarcinoma
      Cells: Cytochrome P450 Expression and Induction by Nuclear Receptor Agonists.
AB  - Enzymatic conversion of most xenobiotic compounds is accomplished by hepatocytes
      in the liver, which are also an important target for the manifestation of the
      toxic effects of foreign compounds. Most cell lines derived from hepatocytes lack
      important toxifying or detoxifying enzymes or are defective in signaling pathways
      that regulate expression and activity of these enzymes. On the other hand, the
      use of primary human hepatocytes is complicated by scarce availability of cells
      and high interdonor variability. Thus, analyses of drug metabolism and
      hepatotoxicity in vitro are a difficult task. The cell line HC-AFW1 was isolated
      from a pediatric hepatocellular carcinoma and so far has been used for
      tumorigenicity and chemotherapy resistance studies. Here, a comprehensive
      characterization of xenobiotic metabolism in HC-AFW1 cells is presented along
      with studies on the functionality of the most important transcriptional
      regulators of drug-metabolizing enzymes. Results from HC-AFW1 cells were compared
      with commercially available HepaRG cells and cultured primary human hepatocytes.
      Data show that the nuclear receptors and xenosensors AHR (aryl hydrocarbon
      receptor), CAR (constitutive androstane receptor), PXR (pregnane-X-receptor),
      NRF2 [nuclear factor (erythroid-derived 2)-like 2], and PPARalpha (peroxisome
      proliferator-activated receptor alpha) are functional in HC-AFW1 cells,
      comparable to HepaRG and primary cells. HC-AFW1 cells possess considerable
      activities of different cytochrome P450 enzymes, which, however, are lower than
      corresponding enzyme activities in HepaRG cells or primary hepatocytes. In
      summary, HC-AFW1 are a new promising tool for studying the mechanisms of the
      regulation of drug metabolism in human liver cells in vitro. 

PMID- 26310805
TI  - Algoriella xinjiangensis gen. nov., sp. nov., a new psychrotolerant bacterium of
      the family Flavobacteriaceae.
AB  - An aerobic, Gram-stain negative, non-spore-forming and psychrotolerant bacterium,
      designated strain XJ109(T), was isolated from a sewage water sample collected
      from Xinjiang Uigur Autonomous Region, China. Phylogenetic analysis based on 16S
      rRNA gene sequence indicated that strain XJ109(T) represents a novel member of
      the family Flavobacteriaceae. The strain showed 95.5 % similarity with the 16S
      rRNA gene sequence of Empedobacter brevis LMG 4011(T), 95.4% with Chishuiella
      changwenlii BY4(T), 95.3% with Empedobacter falsenii NF 993(T) and 92.3% with
      Weeksella virosa DSM 16922(T). Strain XJ109(T) showed the common phenotypic and
      chemotaxonomic characteristics of the family Flavobacteriaceae, containing
      menaquinone-6 (MK-6) as the predominant respiratory quinone and iso-C17:0 3OH and
      iso-C15:0 as the major fatty acids. The polar lipid profile consisted of
      phosphatidylethanolamine, one unidentified phospholipid and two unidentified
      lipids. The genomic DNA G+C content was 38.0 mol%. Strain XJ109(T) was positive
      for catalase and oxidase activities, and it was observed to grow at 4-30  degrees
      C (optimal 16-20  degrees C), pH 6.5-10.0 (optimal 7.0-7.5) and in media
      containing 0-2.0% (w/v) NaCl (optimal 0.5 %). On the basis of the polyphasic
      evidence presented, strain XJ109(T) is considered to represent a novel genus and
      species of the family Flavobacteriaceae, for which the name Algoriella
      xinjiangensis gen. nov., sp. nov. is proposed. The type strain is XJ109(T)
      (=CGMCC 1.10229(T)=JCM 16590(T)).

PMID- 26310806
TI  - Predicting protein function via downward random walks on a gene ontology.
AB  - BACKGROUND: High-throughput bio-techniques accumulate ever-increasing amount of
      genomic and proteomic data. These data are far from being functionally
      characterized, despite the advances in gene (or gene's product proteins)
      functional annotations. Due to experimental techniques and to the research bias
      in biology, the regularly updated functional annotation databases, i.e., the Gene
      Ontology (GO), are far from being complete. Given the importance of protein
      functions for biological studies and drug design, proteins should be more
      comprehensively and precisely annotated. RESULTS: We proposed downward Random
      Walks (dRW) to predict missing (or new) functions of partially annotated
      proteins. Particularly, we apply downward random walks with restart on the GO
      directed acyclic graph, along with the available functions of a protein, to
      estimate the probability of missing functions. To further boost the prediction
      accuracy, we extend dRW to dRW-kNN. dRW-kNN computes the semantic similarity
      between proteins based on the functional annotations of proteins; it then
      predicts functions based on the functions estimated by dRW, together with the
      functions associated with the k nearest proteins. Our proposed models can predict
      two kinds of missing functions: (i) the ones that are missing for a protein but
      associated with other proteins of interest; (ii) the ones that are not available
      for any protein of interest, but exist in the GO hierarchy. Experimental results
      on the proteins of Yeast and Human show that dRW and dRW-kNN can replenish
      functions more accurately than other related approaches, especially for sparse
      functions associated with no more than 10 proteins. CONCLUSION: The empirical
      study shows that the semantic similarity between GO terms and the ontology
      hierarchy play important roles in predicting protein function. The proposed dRW
      and dRW-kNN can serve as tools for replenishing functions of partially annotated
      proteins.

PMID- 26310807
TI  - 9-cis-retinoic acid improves sensitivity to platelet-derived growth factor-BB via
      RXRalpha and SHP-1 in diabetic retinopathy.
AB  - Diabetic retinopathy (DR) is one of the most common complications of diabetes
      mellitus. But few efficient therapeutic methods have been reported. This study
      discussed the functions of 9-cis-retinoic acid (9-cis-RA) in sensitizing retinal
      pericytes to platelet-derived growth factor (PDGF)-BB. Using streptozotocin (STZ)
      induced diabetic mice and high glucose-treated bovine retinal pericytes (BRPC),
      we analyzed the impacts of 9-cis-RA by detecting cell apoptosis via DNA
      fragmentation assay and detecting related factors through adenovirus or
      lentivirus infection and western blot. Results showed that in retinas of STZ
      induced diabetic mice, 9-cis-RA significantly inhibited expression of SHP-1 (P <
      0.01), thus promoting p-AKT and p-ERK1/2, which reflected the improved
      sensitivity to PDGF-BB. In BRPC, 9-cis-RA also improved sensitivity to PDGF-BB
      and suppressed cell apoptosis (P < 0.01) via down-regulating SHP-1. Further
      mechanism analyses showed that the efficient functioning of 9-cis-RA relied on
      the existence of its receptor, retinoic X receptor alpha (RXRalpha), independent
      of the previous reported protein kinase C delta (PKCdelta)/SHP-1 axis. Because 9
      cis-RA could not inhibit SHP-1 or improve sensitivity to PDGF-BB when RXRalpha
      was knocked down, while it still suppressed SHP-1 after overexpression of
      PKCdelta. Taken together, these results indicated the vital roles of 9-cis-RA in
      improving sensitivity to PDGF-BB of retinal pericytes in DR, and provided basic
      evidences of new therapeutic targets like RXRalpha for further DR treatment.

PMID- 26310808
TI  - Local Anti-miR Delivery: The Latest in the Arsenal of Drug-Eluting Stents.

PMID- 26310809
TI  - Relax: It's Not All About Degradation.

PMID- 26310810
TI  - Carotid Ultrasound Phenotypes Are Biologically Distinct.

PMID- 26310811
TI  - Metabolic Flexibility and Dysfunction in Cardiovascular Cells.

PMID- 26310812
TI  - The impact of sarcopenia on survival and complications in surgical oncology: A
      review of the current literature.
AB  - Sarcopenia is the subclinical loss of skeletal muscle and strength and has been
      extensively studied in both the cancer and surgical literature. Specifically,
      sarcopenia has gained significant recognition as an important prognostic factor
      for both complications and survival in cancer patients. Herein, we review the
      current literature to date highlighting the specific impact of sarcopenia in
      patients undergoing oncologic procedures.

PMID- 26310813
TI  - Cryptotanshinone, a novel tumor angiogenesis inhibitor, destabilizes tumor
      necrosis factor-alpha mRNA via decreasing nuclear-cytoplasmic translocation of
      RNA-binding protein HuR.
AB  - Cryptotanshinone (CT), one major lipophilic component isolated from Salvia
      miltiorrhiza Bunge, has shown to possess chemopreventive properties against
      various types of cancer cells. In this study, CT was shown to be a potent anti
      angiogenic agent in zebrafish, and mouse models and could limit tumor growth by
      inhibiting tumor angiogenesis. We further found that CT could inhibit the
      proliferation, migration, angiogenic sprouting, and tube formation of HUVECs. In
      addition, we demonstrated that CT could lower the level of TNF-alpha due to the
      destabilization of TNF-alpha mRNA, which associated with regulating 3'
      untranslated region (3'-UTR) of TNF-alpha and preventing the translocation of RNA
      binding protein, HuR, from the nucleus to the cytoplasm. Moreover, the underlying
      mechanism responsible for the regulation in angiogenesis by CT was partially
      related to the suppression of NF-kappaB, and STAT3 activity. Based on the
      abilities of CT in targeting tumor cells, inhibiting angiogenesis, and destroying
      tumor vasculature, CT is worthy of further investigation for preventive, and
      therapeutic purposes in cancer. (c) 2015 Wiley Periodicals, Inc.

PMID- 26310814
TI  - The role of HOXC6 in prostate cancer development.
AB  - BACKGROUND: Homeobox (HOX) genes, which are involved in organ development and
      homeostasis, have been shown to be involved in normal prostate- and PCa
      development. In this study, we investigate the expression levels of the HOX A-D
      genes in PCa. The functional relevance and potential of HOX gene as biomarkers
      are explored. METHODS: We evaluated HOX gene expression in prostate tissues of
      different grade and stage and related the outcome to clinical parameters. We
      analyzed AR regulation and function of HOXC6 in PCa cell lines. We developed a
      urine-based HOXC6 mRNA assay for diagnostic purposes. RESULTS: HOXC6 was one of
      the most upregulated HOX genes in all primary, metastasized, and castration
      resistant PCa. HOXC6 upregulation was specific to the epithelial component of
      PCa, and HOXC6 was shown to be involved in epithelial cell proliferation. HOXC6
      expression was not influenced by androgens nor by treatments targeting the AR
      signaling pathway. HOXC6 expression was not related to a prognosis after radical
      prostatectomy, that is, biochemical or local recurrence. We successfully
      developed an assay for HOXC6 mRNA detection in urine and confirmed that HOXC6
      levels are higher in PCa patients. CONCLUSIONS: HOXC6 has a role in all PCa
      stages, particularly in PCa cell proliferation. Due to its stable expression,
      HOXC6 is a novel candidate biomarker for PCa not only in early detection but also
      for monitoring of progression or response to therapy.

PMID- 26310815
TI  - Hypoxia: a key player in antitumor immune response. A Review in the Theme:
      Cellular Responses to Hypoxia.
AB  - The tumor microenvironment is a complex system, playing an important role in
      tumor development and progression. Besides cellular stromal components,
      extracellular matrix fibers, cytokines, and other metabolic mediators are also
      involved. In this review we outline the potential role of hypoxia, a major
      feature of most solid tumors, within the tumor microenvironment and how it
      contributes to immune resistance and immune suppression/tolerance and can be
      detrimental to antitumor effector cell functions. We also outline how hypoxic
      stress influences immunosuppressive pathways involving macrophages, myeloid
      derived suppressor cells, T regulatory cells, and immune checkpoints and how it
      may confer tumor resistance. Finally, we discuss how microenvironmental hypoxia
      poses both obstacles and opportunities for new therapeutic immune interventions. 

PMID- 26310816
TI  - Deep proteomic profiling of vasopressin-sensitive collecting duct cells. I.
      Virtual Western blots and molecular weight distributions.
AB  - The mouse mpkCCD cell line is a continuous cultured epithelial cell line with
      characteristics of renal collecting duct principal cells. This line is widely
      used to study epithelial transport and its regulation. To provide a data resource
      useful for experimental design and interpretation in studies using mpkCCD cells,
      we have carried out "deep" proteomic profiling of these cells using three levels
      of fractionation (differential centrifugation, SDS-PAGE, and HPLC) followed by
      tandem mass spectrometry to identify and quantify proteins. The analysis of all
      resulting samples generated 34.6 gigabytes of spectral data. As a result, we
      identified 6,766 proteins in mpkCCD cells at a high level of stringency. These
      proteins are expressed over eight orders of magnitude of protein abundance. The
      data are provided to users as a public data base
      (https://helixweb.nih.gov/ESBL/Database/mpkFractions/). The mass spectrometry
      data were mapped back to their gel slices to generate "virtual Western blots" for
      each protein. For most of the 6,766 proteins, the apparent molecular weight from
      SDS-PAGE agreed closely with the calculated molecular weight. However, a
      substantial fraction (>15%) of proteins was found to run aberrantly, with much
      higher or much lower mobilities than predicted. These proteins were analyzed to
      identify mechanisms responsible for altered mobility on SDS-PAGE, including high
      or low isoelectric point, high or low hydrophobicity, physiological cleavage,
      residence in the lysosome, posttranslational modifications, and expression of
      alternative isoforms due to alternative exon usage. Additionally, this analysis
      identified a previously unrecognized isoform of aquaporin-2 with apparent
      molecular mass <20 kDa. 

PMID- 26310817
TI  - Deep proteomic profiling of vasopressin-sensitive collecting duct cells. II.
      Bioinformatic analysis of vasopressin signaling.
AB  - Vasopressin controls osmotic water transport in the renal collecting duct through
      regulation of aquaporin-2 (AQP2). We carried out bioinformatic analysis of
      quantitative proteomic data from the accompanying article to investigate the
      mechanisms involved. The experiments used stable isotope labeling by amino acids
      in cell culture in cultured mpkCCD cells to quantify each protein species in each
      of five differential-centrifugation (DC) fractions with or without the
      vasopressin analog 1-desamino-8-d-arginine-vasopressin (dDAVP). The mass
      spectrometry data and parallel Western blot experiments confirmed that dDAVP
      addition is associated with an increase in AQP2 abundance in the 17,000-g pellet
      and a corresponding decrease in the 200,000-g pellet. Remarkably, all subunits of
      the cytoplasmic ribosome also increased in the 17,000-g pellet in response to
      dDAVP (P < 10(-34)), with a concomitant decrease in the 200,000-g pellet.
      Eukaryotic translation initiation complex 3 (eIF3) subunits underwent parallel
      changes (P < 10(-6)). These findings are consistent with translocation of
      assembled ribosomes and eIF3 complexes into the rough endoplasmic reticulum in
      response to dDAVP. Conversely, there was a systematic decrease in small GTPase
      abundances in the 17,000-g fraction. In contrast, most proteins, including
      protein kinases, showed no systematic redistribution among DC fractions. Of the
      521 protein kinases coded by the mouse genome, 246 were identified, but many
      fewer were found to colocalize with AQP2 among DC fractions. Bayes' rule was used
      to integrate the new colocalization data with prior data to identify protein
      kinases most likely to phosphorylate aquaporin-2 at Ser(256) (Camk2b > Camk2d >
      Prkaca) and Ser(261) (Mapk1 = Mapk3 > Mapk14). 

PMID- 26310819
TI  - Postoperative pain control in cats: clinical trials with pre-emptive lidocaine
      epidural co-administered with morphine or methadone.
AB  - Objectives The aim of the study was to evaluate the effectiveness of epidural
      lidocaine in combination with either methadone or morphine for postoperative
      analgesia in cats undergoing ovariohysterectomy. Methods Under general
      anesthesia, 24 cats that underwent ovariohysterectomy were randomly allocated
      into three treatment groups of eight each. Treatment 1 included 2% lidocaine (4.0
      mg/kg); treatment 2 included lidocaine and methadone (4.0 mg/kg and 0.3 mg/kg,
      respectively); and treatment 3 included lidocaine and morphine (4.0 mg/kg and 0.1
      mg/kg, respectively). All drugs were injected in a total volume of 0.25 ml/kg via
      the lumbosacral route in all cats. During the anesthetic and surgical periods,
      the physiologic variables (respiratory and heart rate, arterial blood pressure
      and rectal temperature) were measured at intervals of time zero, 10 mins, 20
      mins, 30 mins, 60 mins and 120 mins. After cats had recovered from anesthesia, a
      multidimensional composite pain scale was used to assess postoperative analgesia
      2, 4, 8, 12, 18 and 24 h after epidural. Results The time to first rescue
      analgesic was significantly ( P <0.05) prolonged in cats that received both
      lidocaine and methadone or lidocaine and morphine treatments compared with those
      that received lidocaine treatment alone. All cats that received lidocaine
      treatment alone required rescue analgesic within 2 h of epidural injections. All
      treatments produced significant cardiovascular and respiratory changes but they
      were within an acceptable range for healthy animals during the surgical period.
      Conclusions and relevance The two combinations administered via epidural allowed
      ovariohysterectomy with sufficient analgesia in cats, and both induced prolonged
      postoperative analgesia.

PMID- 26310820
TI  - Seven-day storage of pneumatically dissected Descemet's endothelial grafts with
      and without Dua's layer.
AB  - PURPOSE: To evaluate the efficacy of big-bubble (BB) technique in separating
      Dua's layer together with the Descemet's membrane endothelial (DE) graft and the
      effect of 7-day storage of the prepared tissues on the endothelial cells. METHOD:
      This is an experimental study in which 21 human corneo-scleral tissues unsuitable
      for transplantation were used. Grafts were mounted on artificial chamber;
      epithelial side-up with BB technique was used to detach the DE graft. The
      resultant tissues were stored in tissue culture medium for 7 days. Dua's layer
      presence, endothelial cell density (ECD), endothelial cell loss and viability
      were assessed after the dissection and at 7 days after storage. RESULTS: Complete
      detachment of DE grafts was achieved in 20 cases (95.24%). Histological analysis
      revealed Dua's layer presence in 14 cases (70%). The mean ECD for the corneas
      before dissection was 2375 +/- 338 cells/mm(2) with significant reduction to 2200
      +/- 319 cells/mm(2) (p < 0.00001) with endothelial cell loss of 7.3 +/- 3.5% and
      non-viable cells of 6.5 +/- 2.5% at the end of the 7-day storage. On comparing
      the dissected DE grafts with Dua's layer versus those without at 1 day after
      dissection and at 7 days after storage, we found no statistically significant
      changes in endothelial cell loss (p = 0.387; p = 0.836 respectively) and non
      viable cells percentage (p = 0.180; p = 0.260, respectively). CONCLUSION: Big
      bubble technique is reproducible in dissecting DE grafts with minimal damage to
      the endothelial cells. The percentage of endothelial cell loss and non-viable
      cells is similar in the DE grafts with/without Dua's layer after 7-day storage.

PMID- 26310818
TI  - Prostaglandin E2 activates the mTORC1 pathway through an EP4/cAMP/PKA- and
      EP1/Ca2+-mediated mechanism in the human pancreatic carcinoma cell line PANC-1.
AB  - Obesity, a known risk factor for pancreatic cancer, is associated with
      inflammation and insulin resistance. Proinflammatory prostaglandin E2 (PGE2) and
      elevated insulin-like growth factor type 1 (IGF-1), related to insulin
      resistance, are shown to play critical roles in pancreatic cancer progression. We
      aimed to explore a potential cross talk between PGE2 signaling and the IGF
      1/Akt/mammalian target of rapamycin complex 1 (mTORC1) pathway in pancreatic
      cancer, which may be a key to unraveling the obesity-cancer link. In PANC-1 human
      pancreatic cancer cells, we showed that PGE2 stimulated mTORC1 activity
      independently of Akt, as evaluated by downstream signaling events. Subsequently,
      using pharmacological and genetic approaches, we demonstrated that PGE2-induced
      mTORC1 activation is mediated by the EP4/cAMP/PKA pathway, as well as an
      EP1/Ca(2+)-dependent pathway. The cooperative roles of the two pathways were
      supported by the maximal inhibition achieved with the combined pharmacological
      blockade, and the coexistence of highly expressed EP1 (mediating the Ca(2+)
      response) and EP2 or EP4 (mediating the cAMP/PKA pathway) in PANC-1 cells and in
      the prostate cancer line PC-3, which also robustly exhibited PGE2-induced mTORC1
      activation, as identified from a screen in various cancer cell lines.
      Importantly, we showed a reinforcing interaction between PGE2 and IGF-1 on mTORC1
      signaling, with an increase in IL-23 production as a cellular outcome. Our data
      reveal a previously unrecognized mechanism of PGE2-stimulated mTORC1 activation
      mediated by EP4/cAMP/PKA and EP1/Ca(2+) signaling, which may be of great
      importance in elucidating the promoting effects of obesity in pancreatic cancer.
      Ultimately, a precise understanding of these molecular links may provide novel
      targets for efficacious interventions devoid of adverse effects. 

PMID- 26310821
TI  - Conditional Ultrasound Sensitivity of Poly[(N-isopropylacrylamide)-co-(vinyl
      imidazole)] Microgels for Controlled Lipase Release.
AB  - Triggering the release of cargo from a polymer network by ultrasonication as an
      external, noninvasive stimulus can be an interesting concept for on-demand
      release. Here, it is shown that, in pH- and thermosensitive microgels, the
      ultrasound sensitivity of the polymer network depends on the external conditions.
      Crosslinked poly[(N-isopropylacrylamide)-co-(vinyl imidazole)] microgels showed a
      volume phase transition temperature (VPTT) of 25-50  degrees C, which increases
      with decreasing pH. Above the VPTT the polymer chains are collapsed, while below
      VPTT they are extended. Only in the case of maximum observed swelling, where the
      polymer chains are expanded, the microgels are mechanically fragmented through
      ultrasonication. In contrast, when the polymer chains are partially collapsed it
      is not possible to manipulate the microgels by ultrasound. Additionally, the
      ultrasound-induced on-demand release of wheat germ lipase from the microgels
      could be demonstrated successfully. The principle of conditional ultrasound
      sensitivity is likely to be general and can be used for selection of matrix-cargo
      combinations.

PMID- 26310822
TI  - Aspalathin improves glucose and lipid metabolism in 3T3-L1 adipocytes exposed to
      palmitate.
AB  - SCOPE: Saturated-free fatty acids, such as palmitate, are associated with insulin
      resistance. This study aimed to establish if an aspalathin-enriched green rooibos
      extract (GRE) and, its major flavanoid, aspalathin (ASP) could contribute
      significantly to the amelioration of experimentally induced insulin resistance in
      3T3-L1 adipocytes. METHODS AND RESULTS: 3T3-L1 adipocytes were cultured in DMEM
      containing 0.75 mM palmitate for 16 h to induce insulin resistance before
      treatment for 3 h with GRE (10 MUg/mL) or ASP (10 MUM). GRE and ASP reversed the
      palmitate-induced insulin resistance. At a protein level GRE and ASP suppressed
      nuclear factor kappa beta (NF-kappaB), insulin receptor substrate one (serine
      307) (IRS1 (Ser (307) )) and AMP-activated protein kinase phosphorylation and
      increased serine/threonine kinase AKT (AKT) activation, while only GRE increased
      glucose transporter four (Glut4) protein expression. Peroxisome proliferator
      activated receptor alpha and gamma (PPARalpha and gamma), and carnitine
      palmitoyltransferase one (CPT1) expression were increased by ASP alone.
      CONCLUSION: Together these effects offer a plausible explanation for the
      ameliorative effect of GRE and ASP on insulin-resistance, an underlying cause for
      obesity and type 2 diabetes.

PMID- 26310824
TI  - An immunological view of chemotherapy.

PMID- 26310823
TI  - Identification of a novel actin-dependent signal transducing module allows for
      the targeted degradation of GLI1.
AB  - The Down syndrome-associated DYRK1A kinase has been reported as a stimulator of
      the developmentally important Hedgehog (Hh) pathway, but cells from Down syndrome
      patients paradoxically display reduced Hh signalling activity. Here we find that
      DYRK1A stimulates GLI transcription factor activity through phosphorylation of
      general nuclear localization clusters. In contrast, in vivo and in vitro
      experiments reveal that DYRK1A kinase can also function as an inhibitor of
      endogenous Hh signalling by negatively regulating ABLIM proteins, the actin
      cytoskeleton and the transcriptional co-activator MKL1 (MAL). As a final effector
      of the DYRK1A-ABLIM-actin-MKL1 sequence, we identify the MKL1 interactor Jumonji
      domain demethylase 1A (JMJD1A) as a novel Hh pathway component stabilizing the
      GLI1 protein in a demethylase-independent manner. Furthermore, a Jumonji-specific
      small-molecule antagonist represents a novel and powerful inhibitor of Hh signal
      transduction by inducing GLI1 protein degradation in vitro and in vivo. 

PMID- 26310825
TI  - Pharmacokinetics of Memantine after a Single and Multiple Dose of Oral and Patch
      Administration in Rats.
AB  - Memantine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist
      used to treat Alzheimer's disease. We investigated memantine pharmacokinetics
      after oral, IV and patch administration in rats, and compared memantine
      pharmacokinetics after multiple- or single-dose oral and transdermal
      administration. Venous blood was collected at preset intervals in single- and
      multiple-dose studies. Non-compartmental pharmacokinetics was analysed for all
      formulations. The oral, IV and patch memantine doses were 10 mg/kg, 2 mg/kg and
      8.21 +/- 0.89 mg/kg, respectively. The maximum plasma concentration was lower and
      the half-life longer after patch administration than oral and IV administration.
      Memantine bioavailability was 41 and 63% for oral and patch administration,
      respectively. Steady state was achieved around 24 hr for oral and patch
      administration. The mean AUC increased after oral or patch administration from
      single to multiple dose. The memantine patch formulation displayed a longer
      duration of action and lower peak plasma concentration. However, drug exposure
      was similar to the oral formulation at each dose. Additionally, the memantine
      patch formulation displayed a smaller interindividual variability and lower
      accumulation than the oral formulation. 

PMID- 26310826
TI  - Patient Outcomes and Spinal Cord Stimulation: A Retrospective Case Series
      Evaluating Patient Satisfaction, Pain Scores, and Opioid Requirements.
AB  - INTRODUCTION: Spinal cord stimulators (SCS) are used to treat various chronic
      pain states. Establishing patient outcomes in terms of pain control, opioid
      medication use, and overall satisfaction is vital in maintaining SCS's role in
      clinical practice. METHODS: All patients who underwent SCS implantation between
      January 2001 and December 2011 at a tertiary academic pain medicine center were
      included if he or she underwent permanent cervical or thoracolumbar dorsal column
      SCS implantation and age was 18 or greater. For the 199 patients who met
      inclusion criteria, data were collected retrospectively. Preimplant information
      included indication for implantation, Numeric Rating Scale (NRS) score, and dose
      in oral morphine equivalents (OME). Postimplant NRS score was recorded at 6
      months and 1 year. OME requirement and patient satisfaction were determined at 1
      year postimplantation. RESULTS: This data set showed an overall decrease in OME
      requirements and NRS scores at both 6 months and 1 year. These differences were
      statistically significant (P < 0.01) compared to preimplantation values.
      Additionally, 84.27% of patients were satisfied with their implants at 1 year.
      Patient outcomes were analyzed further in respect to implant indication; groups
      included failed back surgery syndrome (FBSS), complex regional pain syndrome
      (CRPS), angina, and other. For all groups, there were statistically significant
      (P < 0.01) decreases in NRS scores at 6 months and 1 year. In the FBSS and CRPS
      groups, statistically significant (P < 0.02) decreases in OME usage existed.
      CONCLUSION: Retrospective review of patients with spinal cord stimulators
      revealed OME reduction at 1 year for those patients in the FBSS and CRPS groups;
      patient satisfaction at 1 year and NRS score reduction at 6 months and 1 year
      were statistically significant for all groups.

PMID- 26310827
TI  - Tumor Growth Inhibition via Occlusion of Tumor Vasculature Induced by N
      Terminally PEGylated Retargeted Tissue Factor tTF-NGR.
AB  - tTF-NGR retargets the extracellular domain of tissue factor via a C-terminal
      peptide GNGRAHA, a ligand of the surface protein aminopeptidase N (CD13) and upon
      deamidation of integrin alphavbeta3, to tumor vasculature. tTF-NGR induces tumor
      vascular infarction with consecutive antitumor activity against xenografts and
      selectively inhibits tumor blood flow in cancer patients. Since random PEGylation
      resulted in favorable pharmacodynamics of tTF-NGR, we performed site-directed
      PEGylation of PEG units to the N-terminus of tTF-NGR to further improve the
      antitumor profile of the molecule. Mono-PEGylation to the N-terminus did not
      change the procoagulatory activity of the tTF-NGR molecule as measured by Factor
      X activation. Experiments to characterize pharmacokinetics in mice showed a more
      than 1 log step higher mean area under the curve of PEG20k-tTF-NGR over tTF-NGR.
      Acute (24 h) tolerability upon intravenous application for the mono-PEGylated
      versus non-PEGylated tTF-NGR compounds was comparable. PEG20k-tTF-NGR showed
      clear antitumor efficacy in vivo against human tumor xenografts when systemically
      applied. However, site-directed mono-PEGylation to the N-terminus does not
      unequivocally improve the therapeutic profile of tTF-NGR. 

PMID- 26310828
TI  - Role of HIV-1 Envelope Glycoproteins Conformation and Accessory Proteins on ADCC
      Responses.
AB  - The role of antibody Fc-mediated effector functions in controlling or preventing
      infections by human immunodeficiency type 1 (HIV-1) and simian immunodeficiency
      (SIV) viruses has been recently highlighted in multiple studies. One of those
      effector functions, antibody-dependent cellular cytotoxicity (ADCC) was suggested
      as correlating with decreased HIV-1 acquisition risk in the recent Thai RV144
      vaccine trial. RV144-elicited antibodies with potent ADCC activity were recently
      found to recognize HIV envelope (Env) epitopes exposed upon Env-CD4 interaction.
      However, HIV-1 efficiently limits the exposure of those epitopes by strongly
      downregulating CD4 by both Nef and Vpu accessory proteins, as well as indirectly
      preventing the accumulation of Env at the cell surface by Vpu-mediated BST-2
      antagonism. These accessory proteins were thus proposed to play a critical role
      in decreasing the susceptibility of HIV-infected cells to elimination by ADCC. In
      this review we will summarize these recent findings and discuss the critical role
      that HIV-1 envelope glycoproteins conformation plays on ADCC responses, how these
      responses can be measured in the laboratory, the role of HIV-1-transmission on
      ADCC responses and how this knowledge can be used to develop new strategies aimed
      at targeting HIV-1-infected cells.

PMID- 26310829
TI  - Adenosine deaminase regulates Treg expression in autologous T cell-dendritic cell
      cocultures from patients infected with HIV-1.
AB  - Regulatory T cells have an important role in immune suppression during HIV-1
      infection. As regulatory T cells produce the immunomodulatory molecule adenosine,
      our aim here was to assess the potential of adenosine removal to revert the
      suppression of anti-HIV responses exerted by regulatory T cells. The experimental
      setup consisted of ex vivo cocultures of T and dendritic cells, to which
      adenosine deaminase, an enzyme that hydrolyzes adenosine, was added. In cells
      from healthy individuals, adenosine hydrolysis decreased CD4(+)CD25(hi)
      regulatory T cells. Addition of 5'-N-ethylcarboxamidoadenosine, an adenosine
      receptor agonist, significantly decreased CD4(+)CD25(lo) cells, confirming a
      modulatory role of adenosine acting via adenosine receptors. In autologous
      cocultures of T cells with HIV-1-pulsed dendritic cells, addition of adenosine
      deaminase led to a significant decrease of HIV-1-induced CD4(+)CD25(hi) forkhead
      box p3(+) cells and to a significant enhancement of the HIV-1-specific CD4(+)
      responder T cells. An increase in the effector response was confirmed by the
      enhanced production of CD4(+) and CD8(+) CD25(-)CD45RO(+) memory cell generation
      and secretion of Th1 cytokines, including IFN-gamma and IL-15 and chemokines MIP
      1alpha/CCL3, MIP-1beta/CCL4, and RANTES/CCL5. These ex vivo results show, in a
      physiologically relevant model, that adenosine deaminase is able to enhance HIV-1
      effector responses markedly. The possibility to revert regulatory T cell-mediated
      inhibition of immune responses by use of adenosine deaminase, an enzyme that
      hydrolyzes adenosine, merits attention for restoring T lymphocyte function in HIV
      1 infection. 

PMID- 26310830
TI  - Regulation and trafficking of the HLA-E molecules during monocyte-macrophage
      differentiation.
AB  - HLA-E is a nonclassical HLA-class I molecule whose best known role is to protect
      from the natural killer cells. More recently, an additional function more similar
      to that of classical HLA-class I molecules, i.e., antigen presentation to T
      cells, is emerging. However, much remains to be explored about the intracellular
      trafficking of the HLA-E molecules. With the use of 3 different cellular
      contexts, 2 monocytic cell lines, U937 and THP1, and peripheral blood monocytes,
      we show here a remarkable increase of HLA-E during monocyte-macrophage
      differentiation. This goes independently from the classical HLA-class I, the main
      source of HLA-E-specific peptides, which is found strongly up-regulated upon
      differentiation of peripheral blood monocytes but not at all in the case of U937
      and THP1 cell lines. Although in all cases, there was a moderate increase of HLA
      E expressed in the cell surface, lysis by natural killer cells is comparably
      restored by an anti-NKG2A antibody in untreated as well as in PMA-differentiated
      U937 cells. Instead, the great majority of the HLA-E is retained in the vesicles
      of the autophagy-lysosome network, where they colocalize with the microtubule
      associated protein light chain 3, as well as with the lysosomal-associated
      membrane protein 1. We conclude that differently from the classical HLA-class I
      molecules, the primary destination of the newly synthesized HLA-E molecules in
      macrophages is, rather than the cell membrane, the intracellular autophagy
      lysosomal vesicles where they are stored and where they can encounter the
      exogenous antigens. 

PMID- 26310831
TI  - Pellino-3 promotes endotoxin tolerance and acts as a negative regulator of TLR2
      and TLR4 signaling.
AB  - Development of endotoxin tolerance in macrophages during sepsis reprograms Toll
      like receptor 4 signaling to inhibit proinflammatory cytokines without
      suppressing anti-inflammatory and antimicrobial mediators and protects the host
      from excessive inflammation and tissue damage. However, endotoxin tolerance
      renders septic patients immunocompromised and unable to control secondary
      infections. Although previous studies have revealed the importance of several
      negative regulators of Toll-like receptor signaling in endotoxin tolerance, the
      role of Pellino proteins has not been addressed. The present report shows that
      the induction of endotoxin tolerance in vivo in mice and in vitro in human
      monocytes and THP-1 and MonoMac-6 macrophages increases the expression of Pellino
      3. Overexpression of Pellino-3 in human embryonic kidney 293/Toll-like receptor 2
      or 293/Toll-like receptor 4/myeloid differentiation factor-2 cells inhibited Toll
      like receptor 2/4-mediated activation of nuclear factor-kappaB and induction of
      CXCL-8 mRNA, and Pellino-3 ablation increased these responses. Pellino-3
      deficient THP-1 cells had elevated Toll-like receptor 2/4-driven tumor necrosis
      factor-alpha, interleukin-6 mRNA, and Toll-like receptor 4-driven CCL5 gene
      expression in response to Toll-like receptor agonists and heat-killed Escherichia
      coli and Staphylococcus aureus, cytokines controlled by the MyD88 and Toll
      interleukin-1R domain-containing protein inducing interferon-beta-mediated
      pathways, respectively. In addition, deficiency in Pellino-3 slightly increased
      phagocytosis of heat-killed bacteria. Transfected Pellino-3 inhibited nuclear
      factor-kappaB activation driven by overexpression of MyD88, TIR domain-containing
      adapter inducing interferon-beta, interleukin-1R-associated kinase-1, and tumor
      necrosis factor receptor activator of nuclear factor-kappaB-binding kinase-1, TGF
      beta-activated kinase 1, and tumor necrosis factor receptor-associated factor-6,
      and inhibited interleukin-1R-associated kinase 1 modifications and tumor necrosis
      factor receptor activator of nuclear factor-kappaB-binding kinase 1
      phosphorylation. Finally, Pellino-3 ablation in THP-1 decreased the extent of
      endotoxin tolerization. Thus, Pellino-3 is involved in endotoxin tolerance and
      functions as a negative regulator of Toll-like receptor 2/4 signaling. 

PMID- 26310833
TI  - YKL-40/CHI3L1 drives inflammation on the road of tumor progression.
AB  - Inflammation plays a vital role at different stages of tumor progression. The
      development of tumors is affected by inflammatory mediators produced by the tumor
      and the host. YKL-40/chitinase-3-like-1 protein is often up-regulated in
      inflammation-associated diseases. With the use of chronic inflammatory disease
      systems, we describe the role of YKL-40/chitinase-3-like-1 protein in enhancing
      the inflammatory response and its implications in tumorigenesis. We also discuss
      how pre-existing inflammation enhances tumor growth and metastasis. In this mini
      review, we highlight the effect of YKL-40/chitinase-3-like-1 protein-associated
      inflammation in promoting tumor progression. 

PMID- 26310832
TI  - Staurosporine resistance in inflammatory neutrophils is associated with the
      inhibition of caspase- and proteasome-mediated Mcl-1 degradation.
AB  - Apoptosis resistance in activated neutrophils is known to be associated with
      collateral damage of surrounding tissue, as well as immune and organ dysfunction.
      Thus, the safe removal of neutrophils by apoptosis induction represents a
      prerequisite for the resolution of inflammation. Here, we report that intrinsic
      apoptosis resistance in human neutrophils, isolated from severely injured
      patients, is based on enhanced stabilization of antiapoptotic myeloid cell
      leukemia 1 and subsequent impairment of downstream apoptotic pathways. Whereas
      extrinsic apoptosis induction by the activation of Fas death receptor on
      inflammatory neutrophils was accompanied by caspase- and proteasome-mediated
      myeloid cell leukemia 1 degradation, intrinsic apoptosis induction by
      staurosporine led to a significant stabilization of myeloid cell leukemia 1
      protein, which impeded on truncated forms of B cell lymphoma 2-associated X
      protein and B cell lymphoma 2 homology domain 3-interacting domain death
      translocation and subsequent cytochrome c release from the mitochondria. We show
      further that profound inhibition of myeloid cell leukemia 1 degradation is based
      on the inhibition of caspases and sustained activation of kinases involved in
      cell survival, such as Akt. Accordingly, impeded myeloid cell leukemia 1
      phosphorylation on Ser159 by glycogen synthase kinase 3 and protein
      ubiquitination has been demonstrated. Inhibition of myeloid cell leukemia 1
      activity markedly increased sensitivity to staurosporine-induced cell death.
      Altogether, these results provide new insights into the mechanisms underlying
      myeloid cell leukemia 1-mediated apoptosis resistance to staurosporine under
      inflammatory situations and should be considered for the development of novel
      therapeutic strategies. 

PMID- 26310834
TI  - Computational DNA hole spectroscopy: A new tool to predict mutation hotspots,
      critical base pairs, and disease 'driver' mutations.
AB  - We report on a new technique, computational DNA hole spectroscopy, which creates
      spectra of electron hole probabilities vs. nucleotide position. A hole is a site
      of positive charge created when an electron is removed. Peaks in the hole
      spectrum depict sites where holes tend to localize and potentially trigger a base
      pair mismatch during replication. Our studies of mitochondrial DNA reveal a
      correlation between L-strand hole spectrum peaks and spikes in the human mutation
      spectrum. Importantly, we also find that hole peak positions that do not coincide
      with large variant frequencies often coincide with disease-implicated mutations
      and/or (for coding DNA) encoded conserved amino acids. This enables combining
      hole spectra with variant data to identify critical base pairs and potential
      disease 'driver' mutations. Such integration of DNA hole and variance spectra
      could ultimately prove invaluable for pinpointing critical regions of the vast
      non-protein-coding genome. An observed asymmetry in correlations, between the
      spectrum of human mtDNA variations and the L- and H-strand hole spectra, is
      attributed to asymmetric DNA replication processes that occur for the leading and
      lagging strands. 

PMID- 26310835
TI  - Fracture Mechanism and Toughness Optimization of Macroscopic Thick Graphene Oxide
      Film.
AB  - Combined high strength and toughness of film materials are rather important for
      their industrial applications. As a new class of films, graphene oxide films
      (GOFs) attract intense attention in many applications but are frequently
      divergent, inconsistent, and poorly reproducible in their mechanical properties.
      In this study, we first demonstrate that different chemical compositions and
      assembly structures probably are responsible for the difference in elongations
      between cast GOFs and filtration GOFs. Comprehensive analysis of the morphologies
      and mechanical properties indicates that the enhanced elongation of the thick
      cast GOFs is mainly attributed to the presence of a unique skin-wrinkles-skin
      structure, which more easily forms in cast GOFs than in filtration counterparts.
      On the basis of this finding, we attempt to optimize the strength-toughness
      performance of the cast GOFs by adjusting their structures. With an appropriate
      thickness of 12.5 MUm, the GOFs can achieve an ultrahigh toughness up to 4.37 MJ
      m(-3), which is even comparable to the polymer-toughening graphene/GO-based paper
      like materials. Such an optimization of the mechanical properties from the
      perspective of skin-wrinkles-skin structure appears to be a universal approach
      that could be extended to a variety of other film materials. 

PMID- 26310836
TI  - Effectiveness of ethinylestradiol/drospirenone for premenstrual symptoms in
      Japanese patients with dysmenorrhea: Open-label pilot study.
AB  - AIM: A combined oral contraceptive containing ethinylestradiol 20 ug plus
      drospirenone 3 mg (EE20 + DRSP) in a 24/4 regimen has been shown to alleviate the
      symptoms of premenstrual syndrome and premenstrual dysphoric disorder. This study
      was conducted to evaluate the efficacy of EE20 + DRSP in Japanese patients with
      premenstrual symptoms. MATERIAL AND METHODS: A multicenter, prospective, open
      label, single-arm, phase IV study was performed in Japanese women with
      dysmenorrhea and premenstrual symptoms. They were treated with EE20 + DRSP to
      alleviate the symptoms of dysmenorrhea for six treatment cycles. Premenstrual
      symptoms were evaluated using a Premenstrual Symptoms Questionnaire at baseline
      and after three and six cycles of EE20 + DRSP. The degree of dysmenorrhea was
      also evaluated using a visual analog scale at baseline and after one, three, and
      six cycles of EE20 + DRSP. RESULTS: Forty-eight patients were treated with EE20 +
      DRSP. Most of the premenstrual symptoms were alleviated significantly by three
      and six cycles of EE20 + DRSP treatment. EE20 + DRSP treatment significantly
      improved the severity of premenstrual symptoms. We also confirmed the
      effectiveness of EE20 + DRSP for the treatment for dysmenorrhea. CONCLUSION: This
      study showed that EE20 + DRSP could be a useful treatment strategy for
      premenstrual symptoms in Japanese women.

PMID- 26310837
TI  - Simultaneous beat-to-beat assessment of arterial blood pressure and quality of
      cardiopulmonary resuscitation in out-of-hospital and in-hospital settings.
AB  - OBJECTIVE: The current recommendation for depth and rate of chest compression
      (CC) during cardiopulmonary resuscitation (CPR) is based on limited hemodynamic
      data recorded during human CPR. We have evaluated the possible association
      between CC depth and rate and continuously measured arterial blood pressure
      during adult CPR. METHODS: This prospective study included data from 104 patients
      resuscitated inside or outside hospital. Adequate data on continuously measured
      invasive arterial blood pressure (BP) and the quality of CPR from a defibrillator
      capable recording CPR quality parameters was successful in 39 patients. We used
      logistic regression and mixed effects modeling to identify CC depths and rates
      associated with systolic blood pressure (SBP) >= 85 mm Hg and diastolic blood
      pressure (DBP) >= 30 mm Hg. RESULTS: We analyzed 41,575 compression-BP pairs. The
      values for blood pressure varied greatly between the patients. SBP varied from 25
      to 225 mm Hg and DBP from 2 to 59 mm Hg. CC rate 100-120/min and CC depth >= 60
      mm (without mattress deflection correction) was associated with DBP >= 30 mm Hg
      in both femoral (OR 1.14; 95% CI 1.03, 1.26; p<0.05) and radial (OR 4.70; 95% CI
      3.92, 5.63; p<0.001) recordings. For any given subject there was a weak upward
      trend in blood pressure as CC depth increased. CONCLUSION: Deeper CC does not
      equal higher BP in every patient. The heterogeneity of patients creates a
      challenge to find the optimal way to resuscitate patients individually. CLINICAL
      TRIAL REGISTRATION: Clinicaltrials.gov NCT00951704.

PMID- 26310838
TI  - The Clinical Impact of Ventilator-Associated Events: A Prospective Multi-Center
      Surveillance Study.
AB  - OBJECTIVE: The Centers for Disease Control and Prevention (CDC) has developed an
      approach to ventilator-associated events (VAE) surveillance. Using these methods,
      this study was performed to investigate VAE incidences and to test whether VAEs
      are associated with poorer outcomes in China. DESIGN: A 4-month, prospective
      multicenter surveillance study between April and July 2013. SETTING: Our study
      included 15 adult intensive care units (ICUs) of 15 hospitals in China. PATIENTS:
      Patients admitted to ICUs during the study period METHODS: Patients on mechanical
      ventilation (MV) were monitored for VAEs: ventilator-associated conditions
      (VACs), infection-related ventilator-associated complications (IVACs), and
      possible or probable ventilator-associated pneumonia (VAP). Patients with and
      without VACs were compared with regard to duration of MV, ICU length of stay
      (LOS), overall hospital LOS, and mortality rate. RESULTS: During the study
      period, 2,356 of the 5,256 patients admitted to ICUs received MV for 8,438
      ventilator days. Of these patients, 636 were on MV >2 days. VACs were identified
      in 94 cases (4.0%; 11.1 cases per 1,000 ventilator days), including 31 patients
      with IVACs and 16 with possible VAP but none with probable VAP. Compared with
      patients without VACs, patients with VACs had longer ICU LOS (by 6.2 days),
      longer duration on MV (by 7.7 days), and higher hospital mortality rate (50.0% vs
      27.3%). The mortality rate attributable to VACs was 11.7%. Compared with those
      with VACs alone, patients with IVACs had longer duration on MV and increased ICU
      LOS but no higher mortality rates. CONCLUSIONS: In China, surveillance of VACs
      and IVACs is able to identify MV patients with poorer outcomes. However,
      surveillance of possible and probable VAP can be problematic.

PMID- 26310839
TI  - Thymic stromal lymphopoietin-induced interleukin-17A is involved in the
      development of IgE-mediated atopic dermatitis-like skin lesions in mice.
AB  - Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with
      elevated levels of allergen-specific IgE. Although thymic stromal lymphopoietin
      (TSLP) and interleukin-17A (IL-17A) have been considered as important factors in
      allergic diseases, their relationships in AD have not been fully defined. Here,
      we show the contribution of TSLP-induced IL-17A responses to IgE-mediated AD-like
      skin lesions. BALB/c mice passively sensitized by intraperitoneal injections of
      ovalbumin (OVA)-specific IgE monoclonal antibody (mAb) were challenged with OVA
      applied to the skin six times. Treatment with anti-TSLP mAb during the second to
      sixth challenges inhibited IgE-mediated AD-like skin lesions and IL-17A
      production in lymph nodes. Furthermore, the increased number of IL-17A-producing
      CD4(+) and gammadelta T cells in lymph nodes and neutrophilic inflammation in the
      skin were reduced by anti-TSLP mAb. These findings prompted us to examine the
      roles of IL-17A. Treatment with anti-IL-17A mAb suppressed the AD-like skin
      lesions and neutrophilic inflammation; anti-Gr-1 mAb also inhibited them.
      Furthermore, treatment with CXCR2 antagonist reduced the AD-like skin lesions and
      neutrophilic inflammation accompanied by the reduction of IL-17A production; the
      increased CXCR2 expression in the epidermal cells was suppressed by anti-TSLP
      mAb. Meanwhile, these treatments, except for anti-Gr-1 mAb, inhibited the
      increased mast cell accumulation in the skin. Collectively, the mechanism of IgE
      mediating IL-17A-producing CD4(+) and gammadelta T cells through TSLP by repeated
      antigen challenges is involved in AD-like skin lesions associated with skin
      inflammation, such as neutrophil and mast cell accumulation; TSLP may regulate
      CXCR2 signalling-induced IL-17A production. 

PMID- 26310840
TI  - Preoperative and surgical factors associated with postoperative intensive care
      unit admission following operative treatment for degenerative lumbar spine
      disease.
AB  - PURPOSE: Evaluate the factors associated with postoperative ICU admission in
      patients undergoing surgical management of degenerative lumbar spine disease.
      METHODS: Patients undergoing surgery for degenerative lumbar spine disease were
      enrolled into a prospective registry over a 2-year period. Preoperative variables
      (age, gender, ASA grade, ODI%, CAD, HTN, MI, CHF, DM, BMI, depression, anxiety)
      and surgical variables (instrumentation, arthrodesis, estimated blood loss,
      length of surgery) were collected prospectively. Postoperative ICU admission
      details were retrospectively determined from the electronic medical record.
      Student's t test (continuous variables) and Chi-square test (categorical
      variables) were used to determine the association of each preoperative and
      surgical variable with ICU admission. RESULTS: 808 Patients (273 laminectomy, 535
      laminectomy and fusion) were evaluated. Forty-one (5.1%) patients were found to
      have postoperative ICU admissions. Reasons for admission included blood loss
      (12.2%), cardiac (29.3%), respiratory (19.5%), neurologic (31.7%), and other
      (7.3%). For preoperative variables, female gender (P < 0.001), history of CAD (P
      = 0.003), history of MI (P = 0.008), history of CHF (P = 0.001), age (P = 0.025),
      and ASA grade (P = 0.008) were significantly associated with ICU admission. For
      surgical variables, estimated blood loss (P < 0.001) and length of surgery (P <
      0.001) were significantly associated with ICU admission. CONCLUSIONS: Age, female
      gender, ASA grade, cardiac comorbidities, intraoperative blood loss, and length
      of surgery were associated with increased risk of postoperative ICU admission.
      Knowledge of these factors can aid surgeons in patient selection and preoperative
      discussion with patients about potential need for unexpected admission to the
      ICU.

PMID- 26310841
TI  - Multimodality intraoperative neuromonitoring in extreme lateral interbody fusion.
      Transcranial electrical stimulation as indispensable rearview.
AB  - PURPOSE: To optimize intraoperative neuromonitoring during extreme lateral
      interbody fusion (XLIF) by adding transcranial electrical stimulation with motor
      evoked potential (TESMEP) to previously described monitoring using spontaneous
      EMG (sEMG) and peripheral stimulation (triggered EMG: tEMG). METHODS: Twenty
      three patients with degenerative lumbar scoliosis had XLIF procedures and were
      monitored using sEMG, tEMG and TESMEP. Spontaneous and triggered muscle activity,
      and the MEP of 5 ipsilateral leg muscles, 2 contralateral leg muscles and 1 arm
      muscle were monitored. RESULTS: During XLIF surgery decreased MEP amplitudes were
      measured in 9 patients and in 6 patients sEMG was documented. In 4 patients, both
      events were described. In 30 % of the cases (n = 7), the MEP amplitude decreased
      immediately after breaking of the table and even before skin incision. After
      reduction of the table break, the MEP amplitudes recovered to baseline. In two
      patients, the MEP amplitude deteriorated during distraction of the psoas with the
      retractor, while no events were reported using sEMG and tEMG. Repositioning of
      the retractor led to recovery of the MEP. CONCLUSIONS: Monitoring the complete
      nervous system during an XLIF procedure is found to be helpful since nerve roots,
      lumbar plexus as well as the intradural neural structures may be at risk. TESMEP
      has additional value to sEMG and tEMG during XLIF procedure: (1) it informed
      about otherwise unnoticed events, and (2) it confirmed and added information to
      events measured using sEMG.

PMID- 26310842
TI  - Construct and predictive validity of the German Orebro questionnaire short form
      for psychosocial risk factor screening of patients with low back pain.
AB  - PURPOSE: Recognizing patients at risk of developing chronic low back pain is
      essential for targeted interventions. One of the best researched screening
      instruments for this purpose is the Orebro Musculoskeletal Pain Questionnaire
      (OMSPQ). This work addresses psychometric properties of the German OMSPQ short
      form and its construct and prognostic validity. METHODS: Analyses are based on a
      cluster-randomized trial assessing a risk tailored intervention for patients
      consulting for low back pain in 35 general practices. A total of 360 patients
      consulting for acute and sub-acute back pain, aged 20-60 years, were included.
      All patients received a 10-item German short version of the OMSPQ, and other
      generic instruments (Graded Chronic Pain Scale, Patient Health Questionnaire
      Depression, Hannover Functional Ability Questionnaire, Fear-Avoidance Beliefs
      Questionnaire). The construct validity was assessed based on the factorial
      structure of the items and correlations with generic instruments. The area under
      the curve (AUC), sensitivity and specificity were calculated as measures of
      prognostic validity. RESULTS: OMSPQ items belonging to the same subscale
      correlated highest among each other. The internal consistency of the OMSPQ items
      was 0.80 (Cronbach's alpha). The factorial structure corresponds with theoretic
      expectations. OMSPQ subscales on pain related disability, depression, and fear
      avoidance beliefs correlated highest with their counterpart generic scales. The
      AUC for three OMSPQ-based prediction models ranged from 0.77 to 0.81.
      CONCLUSIONS: Our results support a satisfactory factorial and prognostic validity
      of the German short OMSPQ. The instrument may guide the provision of targeted
      interventions. Further research should link it to targeted treatments.

PMID- 26310843
TI  - Do surgical expectations change depending on first time surgery or reoperation? A
      prospective cohort study in lumbar spine surgery.
AB  - PURPOSE: To assess whether patients undergoing lumbar spine surgery for the first
      time (Group 1) had different expectations from those undergoing lumbar spine
      surgery for a failed previous procedure (Group 2). METHODS: A prospective study
      that included 77 patients. A set of self-reported questionnaires was pre
      operatively administered including VAS, Oswestry Disability Index (ODI), Zung
      Depression Scale and the NASS lumbar spine questionnaire (expectations scale).
      RESULTS: Fifty-six patients in Group 1 and 21 patients in Group 2. Both groups
      had high expectations with regard to the surgical procedure (n.s.). Depressed
      patients, despite being more disabled than non-depressed according to ODI (p
      0.001), had similar expectations than non-depressed patients (n.s.). CONCLUSION:
      Patients' expectations remained very high despite having had a failed previous
      surgery for the same procedure.

PMID- 26310844
TI  - Activation of the aryl hydrocarbon receptor by a component of cigarette smoke
      reduces germ cell proliferation in the human fetal ovary.

PMID- 26310845
TI  - Direct profiling of the phospholipid composition of adult Caenorhabditis elegans
      using whole-body imaging mass spectrometry.
AB  - A protocol for the direct analysis of the phospholipid composition in the whole
      body of adult soil nematode, Caenorhabditis elegans (C. elegans), was developed,
      which combined freeze-cracking of the exoskeletal cuticle and matrix-assisted
      laser desorption/ionization-imaging mass spectrometry (MALDI-IMS). Biomolecules
      in the m/z range from 700 to 900 were more effectively detected in the freeze
      cracked than from simple frozen adult nematode bodies. Different distribution of
      biomolecules was observed in a nematode body when the matrix was applied with a
      sublimation deposition method. The whole-body IMS technique was applied on
      genetically deficient mutant C. elegans to combine whole-body lipidomics and
      genetics, by comparing the fatty acid compositions, especially of the
      phosphatidylcholine (PC) species, between the wild-type and fat-1 mutants, which
      lack the gene encoding an n-3 fatty acid desaturase. A significant reduction of
      PC(20:5/20:5) and PC(20:4/20:5) and a marked increase of PC(20:4/20:4),
      PC(20:3/20:4), and PC(20:3/20:3) were detected in the fat-1 mutants in positive
      ion mode. In addition, phospholipid compositions other than PCs were analyzed in
      negative ion mode. A loss of a possible phosphatidylinositol (PI) with 18:0/20:5
      and a compensative accumulation of putative PI(18:0/20:4) were detected in the
      fat-1 mutants. In conclusion, the whole-body MALDI-IMS technique is useful for
      the profiling of multiple biomolecules in C. elegans in both intra- and inter
      individual levels. 

PMID- 26310846
TI  - Feasibility of ultra-trace determination of bromine and iodine in honey by ICP-MS
      using high sample mass in microwave-induced combustion.
AB  - This work demonstrates the feasibility of ultra-trace determination of halogens
      in biological samples by inductively coupled plasma mass spectrometry (ICP-MS)
      after decomposition by microwave-induced combustion (MIC). The conventional MIC
      method was improved to allow the combustion of samples with mass higher than that
      used in previous works in order to achieve better limits of detection (LODs). The
      applicability of the proposed method for ultra-trace determination of bromine and
      iodine in organic samples was demonstrated here using honey. It was possible to
      decompose up to 1000 mg of honey using microcrystalline cellulose as a combustion
      aid and polyethylene film for sample wrapping. After combustion, analytes were
      absorbed using 50 mmol L(-1) NH4OH and recoveries for Br and I were between 99
      and 104 %, and relative standard deviations were lower than 5 %. Microwave
      assisted alkaline dissolution (MA-AD) was also evaluated for honey sample
      preparation using NH4OH or tetramethylammonium hydroxide solutions. However, the
      LODs for the MA-AD method were unsuitable because the high carbon content in
      digests required a dilution step prior to the analysis by ICP-MS. The LODs
      obtained by MIC were improved from 1143 to 34 ng g(-1) for Br and from 571 to 6.0
      ng g(-1) for I, when compared to the MA-AD method. Furthermore, it was possible
      to decompose up to eight samples simultaneously in 30 min (including the cooling
      step) with very low reagent consumption and consequently lower generation of
      effluents, making MIC method well suited for routine ultra-trace determination of
      Br and I in honey. Graphical Abstract A high mass of honey was efficiently
      digested by MIC for subsequent Br and I determination by ICP-MS. 

PMID- 26310847
TI  - Novel roles for LIX1L in promoting cancer cell proliferation through ROS1
      mediated LIX1L phosphorylation.
AB  - Herein, we report the characterization of Limb expression 1-like, (LIX1L), a
      putative RNA-binding protein (RBP) containing a double-stranded RNA binding
      motif, which is highly expressed in various cancer tissues. Analysis of MALDI
      TOF/TOF mass spectrometry and RNA immunoprecipitation-sequencing of interacting
      proteins and the microRNAs (miRNAs) bound to LIX1L revealed that LIX1L interacts
      with proteins (RIOK1, nucleolin and PABPC4) and miRNAs (has-miRNA-520a-5p, -300, 
      216b, -326, -190a, -548b-3p, -7-5p and -1296) in HEK-293 cells. Moreover, the
      reduction of phosphorylated Tyr(136) (pTyr(136)) in LIX1L through the homeodomain
      peptide, PY136, inhibited LIX1L-induced cell proliferation in vitro, and PY136
      inhibited MKN45 cell proliferation in vivo. We also determined the miRNA-targeted
      genes and showed that was apoptosis induced through the reduction of pTyr(136).
      Moreover, ROS1, HCK, ABL1, ABL2, JAK3, LCK and TYR03 were identified as candidate
      kinases responsible for the phosphorylation of Tyr(136) of LIX1L. These data
      provide novel insights into the biological significance of LIX1L, suggesting that
      this protein might be an RBP, with implications for therapeutic approaches for
      targeting LIX1L in LIX1L-expressing cancer cells. 

PMID- 26310848
TI  - Educational inequalities in smoking over the life cycle: an analysis by cohort
      and gender.
AB  - OBJECTIVES: The study investigates the life cycle patterns of educational
      inequalities in smoking according to gender over three successive generations.
      METHODS: Based on retrospective smoking histories collected by the nationwide
      French Health Barometer survey 2010, we explored educational inequalities in
      smoking at each age, using the relative index of inequality. RESULTS: Educational
      inequalities in smoking increase across cohorts for men and women, corresponding
      to a decline in smoking among the highly educated alongside progression among the
      lower educated. The analysis also shows a life cycle evolution: for all cohorts
      and for men and women, inequalities are considerable during adolescence, then
      start declining from 18 years until the age of peak prevalence (around 25), after
      which they remain stable throughout the life cycle, even tending to rise for the
      most recent cohort. CONCLUSIONS: This analysis contributes to the description of
      the "smoking epidemic" and highlights adolescence and late adulthood as life
      cycle stages with greater inequalities.

PMID- 26310851
TI  - Toxicological Sciences: Measuring the True Impact of the Journal.

PMID- 26310849
TI  - Mangosenone F, A Furanoxanthone from Garciana mangostana, Induces Reactive Oxygen
      Species-Mediated Apoptosis in Lung Cancer Cells and Decreases Xenograft Tumor
      Growth.
AB  - Mangosenone F (MSF), a natural xanthone, was isolated form Carcinia mangotana,
      and a few studies have reported its glycosidase inhibitor effect. In this study
      we investigated the anti lung cancer effect of MSF both in vitro and in vivo. MSF
      inhibited cancer cell cytotoxicity and induced and induced apoptosis via reactive
      oxygen species (ROS) generation in NCI-H460. MSF treatment also showed in
      pronounced release of apoptogenic cytochrome c from the mitochondria to the
      cytosol, downregulation of Bcl-2 and Bcl-xL, and upregulation of Bax, suggesting
      that caspase-mediated pathways were involved in MSF-induced apoptosis. ROS
      activation of the mitogen-activated protein kinase signaling pathway was shown to
      play a predominant role in the apoptosis mechanism of MSF. Compared with
      cisplatin treatment, MSF treatment showed significantly increased inhibition of
      the growth of NCI-H460 cells xenografted in nude mice. Together, these results
      indicate the potential of MSF as a candidate natural anticancer drug by promoting
      ROS production.

PMID- 26310852
TI  - At the Crossroads of Nanotoxicology in vitro: Past Achievements and Current
      Challenges.
AB  - The exponential growth in the employment of nanomaterials (NMs) has given rise to
      the field of nanotoxicology; which evaluates the safety of engineered NMs.
      Initial nanotoxicological studies were limited by a lack of both available
      materials and accurate biodispersion characterization tools. However, the years
      that followed were marked by the development of enhanced synthesis techniques and
      characterization technologies; which are now standard practice for
      nanotoxicological evaluation. Paralleling advances in characterization,
      significant progress was made in correlating specific physical parameters, such
      as size, morphology, or coating, to resultant physiological responses. Although
      great strides have been made to advance the field, nanotoxicology is currently at
      a crossroads and faces a number of obstacles and technical limitations not
      associated with traditional toxicology. Some of the most pressing and influential
      challenges include establishing full characterization requirements,
      standardization of dosimetry, evaluating kinetic rates of ionic dissolution,
      improving in vitro to in vivo predictive efficiencies, and establishing safety
      exposure limits. This Review will discuss both the progress and future directions
      of nanotoxicology: highlighting key previous research successes and exploring
      challenges plaguing the field today. 

PMID- 26310853
TI  - Comparison of measurement methods with a mixed effects procedure accounting for
      replicated evaluations (COM3PARE): method comparison algorithm implementation for
      head and neck IGRT positional verification.
AB  - PURPOSE: Comparison of imaging measurement devices in the absence of a gold
      standard comparator remains a vexing problem; especially in scenarios where
      multiple, non-paired, replicated measurements occur, as in image-guided
      radiotherapy (IGRT). As the number of commercially available IGRT presents a
      challenge to determine whether different IGRT methods may be used
      interchangeably, an unmet need conceptually parsimonious and statistically robust
      method to evaluate the agreement between two methods with replicated
      observations. Consequently, we sought to determine, using an previously reported
      head and neck positional verification dataset, the feasibility and utility of a
      Comparison of Measurement Methods with the Mixed Effects Procedure Accounting for
      Replicated Evaluations (COM3PARE), a unified conceptual schema and analytic
      algorithm based upon Roy's linear mixed effects (LME) model with Kronecker
      product covariance structure in a doubly multivariate set-up, for IGRT method
      comparison. METHODS: An anonymized dataset consisting of 100 paired coordinate
      (X/ measurements from a sequential series of head and neck cancer patients imaged
      near-simultaneously with cone beam CT (CBCT) and kilovoltage X-ray (KVX) imaging
      was used for model implementation. Software-suggested CBCT and KVX shifts for the
      lateral (X), vertical (Y) and longitudinal (Z) dimensions were evaluated for
      bias, inter-method (between-subject variation), intra-method (within-subject
      variation), and overall agreement using with a script implementing COM3PARE with
      the MIXED procedure of the statistical software package SAS (SAS Institute, Cary,
      NC, USA). RESULTS: COM3PARE showed statistically significant bias agreement and
      difference in inter-method between CBCT and KVX was observed in the Z-axis (both
      p - value<0.01). Intra-method and overall agreement differences were noted as
      statistically significant for both the X- and Z-axes (all p - value<0.01). Using
      pre-specified criteria, based on intra-method agreement, CBCT was deemed
      preferable for X-axis positional verification, with KVX preferred for
      superoinferior alignment. CONCLUSIONS: The COM3PARE methodology was validated as
      feasible and useful in this pilot head and neck cancer positional verification
      dataset. COM3PARE represents a flexible and robust standardized analytic
      methodology for IGRT comparison. The implemented SAS script is included to
      encourage other groups to implement COM3PARE in other anatomic sites or IGRT
      platforms.

PMID- 26310854
TI  - The associations between daily spring pollen counts, over-the-counter allergy
      medication sales, and asthma syndrome emergency department visits in New York
      City, 2002-2012.
AB  - BACKGROUND: Many types of tree pollen trigger seasonal allergic illness, but
      their population-level impacts on allergy and asthma morbidity are not well
      established, likely due to the paucity of long records of daily pollen data that
      allow analysis of multi-day effects. Our objective in this study was therefore to
      determine the impacts of individual spring tree pollen types on over-the-counter
      allergy medication sales and asthma emergency department (ED) visits. METHODS:
      Nine clinically-relevant spring tree pollen genera (elm, poplar, maple, birch,
      beech, ash, sycamore/London planetree, oak, and hickory) measured in Armonk, NY,
      were analyzed for their associations with over-the-counter allergy medication
      sales and daily asthma syndrome ED visits from patients' chief complaints or
      diagnosis codes in New York City during March 1st through June 10th, 2002-2012.
      Multi-day impacts of pollen on the outcomes (0-3 days and 0-7 days for the
      medication sales and ED visits, respectively) were estimated using a distributed
      lag Poisson time-series model adjusting for temporal trends, day-of-week,
      weather, and air pollution. For asthma syndrome ED visits, age groups were also
      analyzed. Year-to-year variation in the average peak dates and the 10th-to-90th
      percentile duration between pollen and the outcomes were also examined with
      Spearman's rank correlation. RESULTS: Mid-spring pollen types (maple, birch,
      beech, ash, oak, and sycamore/London planetree) showed the strongest significant
      associations with both outcomes, with cumulative rate ratios up to 2.0 per 0-to
      98th percentile pollen increase (e.g., 1.9 [95% CI: 1.7, 2.1] and 1.7 [95% CI:
      1.5, 1.9] for the medication sales and ED visits, respectively, for ash). Lagged
      associations were longer for asthma syndrome ED visits than for the medication
      sales. Associations were strongest in children (ages 5-17; e.g., a cumulative
      rate ratio of 2.6 [95% CI: 2.1, 3.1] per 0-to-98th percentile increase in ash).
      The average peak dates and durations of some of these mid-spring pollen types
      were also associated with those of the outcomes. CONCLUSIONS: Tree pollen peaking
      in mid-spring exhibit substantive impacts on allergy, and asthma exacerbations,
      particularly in children. Given the narrow time window of these pollen peak
      occurrences, public health and clinical approaches to anticipate and reduce
      allergy/asthma exacerbation should be developed.

PMID- 26310855
TI  - A randomized study of local anesthesia for pain control during intra-articular
      corticosteroid injection in children with arthritis.
AB  - BACKGROUND: Intra-articular corticosteroid injections (IACI) are routinely used
      by pediatric rheumatologists in the treatment of chronic arthritis. Frequently,
      topical anesthetics are used to control procedural pain, but their relative
      efficacy has not been reported. In this study, we evaluated the level of pain
      associated with different anesthetic methods, Numby(r) 900 Iontophoretic Drug
      Delivery System, or EMLA(r) cream, with or without subcutaneous buffered
      lidocaine (SQBL), during IACI of the knee in children with arthritis. METHODS: We
      conducted a prospective study of patients, ages 4 to 21 years old, followed at
      three pediatric rheumatology centers who were undergoing IACI of a knee joint.
      Patients were randomized into two treatment groups: 1) topical anesthetic only
      (EMLA(r) or Numby(r) (E/N)), or 2) topical anesthetic (E/N) and SQBL. Pain was
      assessed at baseline, during topical anesthetic placement, and following the IACI
      (post-procedure). The Faces Pain Scale-Revised (FPS-R), the Face, Leg, Activity,
      Cry, Consolability (FLACC) behavioral scale and the parental global assessment
      (PGA) (0 = best experience, 10 = worst experience) were determined. RESULTS:
      Sixty-three patients (44 females) with a median [IQR] age of 10.8 [IQR = (8.2
      14.4)] years (range 4.7-20 years) with active knee arthritis were consented. FPS
      R post-procedure (P = 0.03), FLACC (P = 0.02) and PGA (P = 0.01) scores were
      significantly lower in females treated with E/N plus SQBL compared to patients
      treated with E/N only. Females in the E/N only group had a significant worsening
      of their baseline pain (p < 0.0004) and a greater magnitude of change in their
      baseline FPS-R scores (p < 0.001) from the procedure compared to females in the
      E/N plus SQBL group who had no worsening of their baseline pain. No significant
      change in pain level or PGA score was found among males in either treatment
      group. Pain scores overall were similar to the oligoarthritis patients, a more
      homogeneous group of patients. Both EMLA(r) (n = 33) and Numby(r) (n = 29) were
      equally well tolerated with no significant difference in median FPS-R
      administration scores overall. CONCLUSION: Our results suggest that a topical
      anesthetic plus SQBL is more effective for injection pain control than topical
      anesthesia only. Further studies addressing pain and anxiety will help determine
      the optimal method of pain control for IACI.

PMID- 26310856
TI  - Climate suitability for European ticks: assessing species distribution models
      against null models and projection under AR5 climate.
AB  - BACKGROUND: There is increasing evidence that the geographic distribution of tick
      species is changing. Whilst correlative Species Distribution Models (SDMs) have
      been used to predict areas that are potentially suitable for ticks, models have
      often been assessed without due consideration for spatial patterns in the data
      that may inflate the influence of predictor variables on species distributions.
      This study used null models to rigorously evaluate the role of climate and the
      potential for climate change to affect future climate suitability for eight
      European tick species, including several important disease vectors. METHODS: We
      undertook a comparative assessment of the performance of Maxent and Mahalanobis
      Distance SDMs based on observed data against those of null models based on null
      species distributions or null climate data. This enabled the identification of
      species whose distributions demonstrate a significant association with climate
      variables. Latest generation (AR5) climate projections were subsequently used to
      project future climate suitability under four Representative Concentration
      Pathways (RCPs). RESULTS: Seven out of eight tick species exhibited strong
      climatic signals within their observed distributions. Future projections intimate
      varying degrees of northward shift in climate suitability for these tick species,
      with the greatest shifts forecasted under the most extreme RCPs. Despite the high
      performance measure obtained for the observed model of Hyalomma lusitanicum, it
      did not perform significantly better than null models; this may result from the
      effects of non-climatic factors on its distribution. CONCLUSIONS: By comparing
      observed SDMs with null models, our results allow confidence that we have
      identified climate signals in tick distributions that are not simply a
      consequence of spatial patterns in the data. Observed climate-driven SDMs for
      seven out of eight species performed significantly better than null models,
      demonstrating the vulnerability of these tick species to the effects of climate
      change in the future.

PMID- 26310858
TI  - Synthesis of Structurally Diverse 2,3-Fused Indoles via Microwave-Assisted AgSbF6
      Catalysed Intramolecular Difunctionalization of o-Alkynylanilines.
AB  - 2,3-Fused indoles are found in numerous natural products and drug molecules.
      Although several elegant methods for the synthesis of this structural motif have
      been reported, long reaction times and harsh conditions are sometimes required,
      and the yields tend to be low. Herein, we report a microwave method for
      straightforward access to various types of 2,3-fused indoles via AgSbF6-catalysed
      intramolecular difunctionalization of o-alkynylanilines. AgSbF6 played a role in
      both the hydroamination step and the imine-formation step. This method, which
      exhibited excellent chemoselectivity (no ring-fused 1,2-dihydroquinolines were
      formed), was used for formal syntheses of the natural products conolidine and
      ervaticine and the antihistamine drug latrepirdine. 

PMID- 26310857
TI  - Arsenic trioxide rewires mantle cell lymphoma response to bortezomib.
AB  - Although most of the mantle cell lymphoma (MCL) patients initially responded well
      to bortezomib (BTZ), the dose-dependent toxicities have greatly limited the
      application of BTZ to MCL. To investigate the efficacy and mechanism of arsenic
      trioxide (ATO) with BTZ in inducing apoptosis of MCL cells, two MCL cell lines,
      along with primary cells from MCL patients (n = 4), were used. Additionally, the
      NOD-SCID mice xenograft model of Jeko-1 cells was established to study the anti
      MCL mechanisms in an in vivo setting. ATO treatment highly improved BTZ capacity
      to inhibit proliferation and induce apoptosis of MCL cells. Furthermore, the
      interaction of Noxa and Mcl-1 leads Bak to release from Mcl-1 or from Bcl-xl,
      which could further activate Bak and Bax and then induce cell apoptosis. We also
      found that when lower doses of BTZ were used in combination with ATO, more
      effective proapoptotic effects in both the cell lines and the primary cells were
      obtained compared to the effects of BTZ used alone at higher doses.
      Simultaneously, the combination of these two drugs delayed the tumor growth in
      mice more effectively than BTZ alone. The cooperative anti-MCL effects of this
      combination therapy both in vitro and in vivo strongly provided a new strategy to
      the clinical treatment of MCL.

PMID- 26310859
TI  - Suppressive effects of the NADPH oxidase inhibitor apocynin on intestinal
      tumorigenesis in obese KK-A(y) and Apc mutant Min mice.
AB  - Obesity is a risk factor for colorectal cancer. The accumulation of abdominal fat
      tissue causes abundant reactive oxygen species production through the activation
      of NADPH oxidase due to excessive insulin stimulation. The enzyme NADPH oxidase
      catalyzes the production of reactive oxygen species and evokes the initiation and
      progression of tumorigenesis. Apocynin is an NADPH oxidase inhibitor that blocks
      the formation of the NADPH oxidase complex (active form). In this study, we
      investigated the effects of apocynin on the development of azoxymethane-induced
      colonic aberrant crypt foci in obese KK-A(y) mice and on the development of
      intestinal polyps in Apc mutant Min mice. Six-week-old KK-A(y) mice were injected
      with azoxymethane (200 MUg/mouse once per week for 3 weeks) and given 250 mg/L
      apocynin or 500 mg/L apocynin in their drinking water for 7 weeks. Six-week-old
      Min mice were also treated with 500 mg/L apocynin for 6 weeks. Treatment with
      apocynin reduced the number of colorectal aberrant crypt foci in KK-A(y) mice by
      21% and the number of intestinal polyps in Min mice by 40% compared with
      untreated mice. Both groups of mice tended to show improved oxidation of serum
      low-density lipoprotein and 8-oxo-2'-deoxyguanosine adducts in their adipose
      tissues. In addition, the inducible nitric oxide synthase mRNA levels in polyp
      tissues decreased. Moreover, apocynin was shown to suppress nuclear factor-kappaB
      transcriptional activity in vitro. These results suggest that apocynin and other
      NADPH oxidase inhibitors may be effective colorectal cancer chemopreventive
      agents. 

PMID- 26310860
TI  - Anti-biofilm activity of ultrashort cinnamic acid peptide derivatives against
      medical device-related pathogens.
AB  - The threat of antimicrobial resistance has placed increasing emphasis on the
      development of innovative approaches to eradicate multidrug-resistant pathogens.
      Biofilm-forming microorganisms, for example, Staphylococcus epidermidis and
      Staphylococcus aureus, are responsible for increased incidence of biomaterial
      infection, extended hospital stays and patient morbidity and mortality. This
      paper highlights the potential of ultrashort tetra-peptide conjugated to
      hydrophobic cinnamic acid derivatives. These peptidomimetic molecules demonstrate
      selective and highly potent activity against resistant biofilm forms of Gram
      positive medical device-related pathogens. 3-(4-Hydroxyphenyl)propionic)-Orn-Orn
      Trp-Trp-NH2 displays particular promise with minimum biofilm eradication
      concentration (MBEC) values of 125 ug/ml against methicillin sensitive (ATCC
      29213) and resistant (ATCC 43300) S. aureus and activity shown against biofilm
      forms of Escherichia coli (MBEC: 1000 ug/ml). Kill kinetics confirms complete
      eradication of established 24-h biofilms at MBEC with 6-h exposure. Reduced cell
      cytotoxicity, relative to Gram-positive pathogens, was proven via tissue culture
      (HaCaT) and haemolysis assays (equine erythrocytes). Existing in nature as part
      of the immune response, antimicrobial peptides display great promise for
      exploitation by the pharmaceutical industry in order to increase the library of
      available therapeutic molecules. Ultrashort variants are particularly promising
      for translation as clinical therapeutics as they are more cost-effective, easier
      to synthesise and can be tailored to specific functional requirements based on
      the primary sequence allowing factors such as spectrum of activity to be varied.

PMID- 26310861
TI  - Long-term outcome in pyridoxine-responsive infantile epilepsy.
AB  - BACKGROUND: Dose regimens of pyridoxine (vitamin B6) for treatment of infantile
      spasms have varied from 200 mg/d to 300 mg/kg/d. Only two long-term outcome
      studies of the treated patients are available. METHODS: We asked all pediatric
      neurologists treating pediatric epilepsy in Finland if they had seen patients
      with pyridoxine-responsive infantile epilepsy. Five children with infantile
      spasms and hypsarrhythmia and one with focal epilepsy were reported as pyridoxine
      responders. Data on clinical presentation and outcome were collected from patient
      charts. RESULTS: All B6 responders had un-known aetiology. Two patients were
      studied for pyridoxal 5'-phosphate oxidase (PNPO) deficiency and showed negative
      results. Ages at seizure onset ranged from 4 to 7 months. The maintenance dose of
      oral pyridoxine was 150 mg/day. Response occurred within 1-to 14 days (mean 5
      days). Two patients were treated with concomitant antiepileptic drugs. Duration
      of pyridoxine therapy varied from 6 weeks to 4 years (mean 26 months). Four
      patients had later seizure recurrence: one at 15 months with motor seizures
      (stopped by valproate), another two in adolescence with focal epilepsy and one at
      20 years with unclassified epilepsy. Intelligence was normal in five patients and
      one had a mild mental deficiency. Follow-up ranged from 8.5 to 24 years.
      CONCLUSIONS: Rare patients with infantile epilepsy but not pyridoxine dependency
      may respond to smaller doses of pyridoxine than reported before. Long-term
      cognitive outcome appears to be good but late seizure recurrence (in adolescence
      or in adulthood) occur. So far it is unknown if the response was determined by
      genetic traits or disease-related factors.

PMID- 26310862
TI  - Failure of an ICD to Deliver Antitachycardia Therapy against Recurrent, Sustained
      Ventricular Tachycardia: What's the Mechanism?

PMID- 26310864
TI  - Young adults' experiences of their parents caring for a relative with dementia.
AB  - AIM: The aim of the present study was to explore the experiences and perceptions
      young adults had of family members who are caring for a relative with dementia.
      METHODS: An exploratory qualitative study with semi-structured interviews was
      carried out and data were collected from 24 young adults recruited through
      purposive sampling. The participants had to have a close relative who was caring
      for an elderly family member with dementia. A content analysis approach was used
      for the verbatim transcription. RESULTS: The findings showed that caring for a
      relative with dementia was perceived as a time-consuming, exhausting and long
      term task. The participants experienced stress and strain, although they were not
      the primary caregivers. Despite their negative perceptions of the task, they were
      willing to take on the responsibility of becoming a primary caregiver in the
      future. However, they intended to seek assistance in meeting their caregiving
      roles and responsibilities. Seeing how their close relative cared for a dependent
      older adult led them to reflect on what they would become in the future.
      Interestingly, although the participants expected their future offspring to take
      care of them when they became old, they did not want to be a burden to their
      children. CONCLUSION: Young adults are the caregivers of tomorrow. Knowing their
      perspective on caregiving is important if health professionals are to help them
      evolve into a caregiving role. It has implications for realizing the goal of
      aging in place. Geriatr Gerontol Int 2016; 16: 873-879.

PMID- 26310865
TI  - Use of the life table to compare mortality in ethnic groups in Amsterdam, the
      Netherlands.
AB  - BACKGROUND: The life table is a valid and frequently used instrument to compare
      the mortality of migrant groups. Most analyses are limited to an overview and
      give only life expectancy; however, further analysis of the life table can give
      more insight into differences in patterns of mortality between groups. METHODS: A
      thorough life table analysis was applied to the mortality data of seven ethnic
      groups by age and gender. RESULTS: Life expectancy is systematically higher in
      migrants compared with the Dutch citizens of Amsterdam. However, between birth
      and the age of 40 the probability of death is higher among non-western migrants
      compared with citizens of western origin. The number of deaths is small among the
      young. This results in very small differences in survival between the groups;
      from birth up to the age of 40 the survival rate is 98.7% for citizens of western
      origin and 98.3% for citizens of non-western origin. In all seven ethnic groups
      over 90.7% of babies, male and female, survive up to the age of 60. In all female
      groups the survival is better than in male groups. Males and females aged 0 to 40
      from Antillean origin are the only exception. CONCLUSION: Life expectancy is
      generally higher in non-western than in western groups. Differences in survival
      between ethnic groups are small up to middle age.

PMID- 26310866
TI  - Periodontitis promotes the proliferation and suppresses the differentiation
      potential of human periodontal ligament stem cells.
AB  - The aim of the present study was to investigate the periodontitis-associated
      changes in the number, proliferation and differentiation potential of human
      periodontal ligament stem cells (PDLSCs). Cultures of human periodontal ligament
      cells (PDLCs) were established from healthy donors and donors with periodontitis.
      The numbers of stem cell were characterized using flow cytometry. PDLSCs were
      isolated from the PDLCs by immunomagnetic bead selection. Colony-forming
      abilities, osteogenic and adipogenic potential, gene expression of cementoblast
      phenotype, alkaline phosphatase activity and in vivo differentiation capacities
      were then evaluated. Periodontitis caused an increase in the proliferation of
      PDLSCs and a decrease in the commitment to the osteoblast lineage. This is
      reflected by changes in the expression of osteoblast markers. When transplanted
      into immunocompromised mice, PDLSCs from the healthy donors exhibited the
      capacity to produce cementum PDL-like structures, whereas, the inflammatory
      PDLSCs transplants predominantly formed connective tissues. In conclusion, the
      data from the present study suggest that periodontitis affects the proliferation
      and differentiation potential of human PDLSCs in vitro and in vivo. 

PMID- 26310867
TI  - Aspirin plus ticlopidine prevented experimental endocarditis due to Enterococcus
      faecalis and Streptococcus gallolyticus.
AB  - Enterococcus faecalis and Streptococcus gallolyticus cause infective endocarditis
      (IE), which can originate from the continuous release or translocation of low
      bacterial numbers into the bloodstream. In this context, IE cannot be prevented
      with antibiotics. We previously demonstrated that aspirin plus ticlopidine
      protected rats from IE due to S. gordonii and Staphylococcus aureus. Here we
      showed that aspirin plus ticlopidine significantly reduced vegetation weight and
      protected 73 and 64% rats (P < 0.005) from IE due to E. faecalis and S.
      gallolyticus, respectively. These results further support the potential use of
      aspirin plus ticlopidine for a global prevention of IE in high-risk patients. 

PMID- 26310868
TI  - Acute liver failure due to zinc phosphide containing rodenticide poisoning:
      Clinical features and prognostic indicators of need for liver transplantation.
AB  - Zinc phosphide (ZnP) containing rodenticide poisoning is a recognized cause of
      acute liver failure (ALF) in India. When standard conservative measures fail, the
      sole option is liver transplantation. Records of 41 patients admitted to a single
      centre with ZnP-induced ALF were reviewed to identify prognostic indicators for
      requirement of liver transplantation. Patients were analyzed in two groups: group
      I (n = 22) consisted of patients who either underwent a liver transplant (n = 14)
      or died without a transplant (n = 8); group II (n = 19) comprised those who
      survived without liver transplantation. International normalized ratio (INR) in
      group I was 9 compared to 3 in group II (p < 0.001). Encephalopathy occurred only
      in group I. Model for End-Stage Liver Disease (MELD) score in group I was 41
      compared to 24 in group II (p < 0.001). MELD score of 36 (sensitivity of 86.7 %,
      specificity of 90 %) or a combination of INR of 6 and encephalopathy (sensitivity
      of 100 %, specificity of 83 %) were the best indicators of mortality. Such
      patients should undergo urgent liver transplantation. 

PMID- 26310869
TI  - The Impact of Cigarette Plain Packaging on Health Warning Salience and
      Perceptions: Implications for Public Health Policy.
AB  - The study employed a mixed methods design using focus group interviews with 6
      student groups and self-administered questionnaires with 1239 students. The
      participants were nonsmoking, current smokers, and quit-smoking teenagers from
      secondary schools and colleges. Focus group revealed that although nonsmoking
      teenagers perceived fear appeals to warning messages, current smokers did not
      perceive fear appeals to health. Black and white backgrounds of the cigarette
      package were chosen as the best color for plain packaging. However, most
      participants suggested various pictorials and a bigger size of pictorial warnings
      for greater and more effective fear appeal. Odds ratio showed that males had 2.43
      times the odds to perceive intention not to smoke. Teenagers who had never smoked
      and those who had quit smoking had 13.27 and 3.61 times the odds, respectively,
      to perceive intention not to smoke. 

PMID- 26310870
TI  - Evaluation of the Vietnamese A6 Mortality Reporting System: All-Cause Mortality.
AB  - There has been no systematic evaluation of Viet Nam's A6 mortality reporting
      system. An evaluation was undertaken in 3 provinces in Viet Nam. Deaths
      identified in the A6 system were compared with deaths identified by an
      independent consensus panel to determine the percentage completeness of the A6
      system. Verbal autopsies (VAs) were conducted for all identified deaths from the
      consensus panels, and the sensitivity and positive predictive value of the A6
      system was assessed. The sensitivity of the A6 system varied depending on the
      cause of death, with the sensitivity of the system being excellent for injury
      (sensitivity = 75.4%), cancer (sensitivity = 66.9%), and circulatory diseases
      (sensitivity = 63.1%). The A6 mortality reporting system performs well in
      relation to its completeness and classification of 3 leading causes of death
      namely, circulatory disease, cancer, and injury. With further enhancements and
      ongoing support from government and donor agencies, the A6 system will be a
      valuable resource.

PMID- 26310871
TI  - Reproductive Health CHOICES for Young Adults with Sickle Cell Disease or Trait:
      Randomized Controlled Trial Outcomes over Two Years.
AB  - Interventions to assist reproductive health decision-making in populations
      affected by sickle cell disease (SCD) or trait (SCT) lack proven efficacy over
      time. Our aim was to compare effects of CHOICES, a Web-based multimedia education
      program on implementing informed reproductive plans, and usual care education (e
      Book) on reproductive knowledge, intention, and behavior over 24 months. We
      randomized 234 participants with SCD (n = 138) or SCT (n = 96) (age 18-35 years,
      35 % male, 94 % African American) to CHOICES and e-Book groups. Participants
      completed a sickle cell-specific reproductive measure before and four times after
      the intervention (6, 12, 18 and 24 months). Compared to the e-Book group the
      CHOICES group had significantly more improvement in knowledge over time (p =
      .004) but not intention (p = .18) or behavior (p = .69). At baseline, 114 (48.7
      %) participants reported having partners who would not put the couple at risk for
      their children inheriting SCD. Of the 116 (49.6 %) at-risk participants, a higher
      poroportion of those who were in the CHOICES group chose partners that reduced
      their risk by the last visit than the e-Book group (p = .04). Study findings
      provide important insights for designing a national trial of the CHOICES
      intervention focusing on subjects whose partner status puts them at risk for
      having a child with SCD.

PMID- 26310872
TI  - Increased exposure to acute thermal stress is associated with a non-linear
      increase in recombination frequency and an independent linear decrease in fitness
      in Drosophila.
AB  - BACKGROUND: Meiotic recombination rate has long been known to be phenotypically
      plastic. How plastic recombination evolves and is maintained remains
      controversial; though a leading model for the evolution of plastic recombination
      rests on the tenet that organismal fitness and recombination frequency are
      negatively correlated. Motivated by the mounting evidence that meiotic
      recombination frequencies increase in response to stress, here we test for a
      negative correlation between fitness and recombination frequency. Specifically,
      the fitness-associated recombination model (FAR) predicts that if stress
      increases meiotic recombination frequency, then increasing exposure to stressful
      conditions will yield an increasing magnitude of the recombinational response,
      while concomitantly decreasing fitness. RESULTS: We use heat shock as a stressor
      to test this prediction in Drosophila melanogaster. We find that increased
      exposure to heat shock conditions is associated with a non-linear increase in
      meiotic recombination frequency. We also find an independent effect of heat shock
      on organismal fitness, with fitness decreasing with increased duration of thermal
      stress. CONCLUSIONS: Our results thus support the foundation of the FAR model for
      the evolution of plastic recombination. Our data also suggest that modulating
      recombination frequency is one mechanism by which organisms can rapidly respond
      to environmental cues and confer increased adaptive potential to their offspring.

PMID- 26310873
TI  - Pattern-induced expectation bias in visual anticipation of action outcomes.
AB  - When anticipating an opponent's action intention, athletes may rely on both
      kinematic and contextual cues. Here we show that patterns of previous action
      outcomes (i.e., a contextual cue) bias visual anticipation of action outcome in
      subsequent trials. In two video-based experiments, skilled players and novices
      were presented with volleyball attacks stopping 360ms (Exp. 1) or 280ms (Exp. 2)
      before an attacker's hand-ball-contact and they were asked to predict the type of
      attack (smash or lob). Attacks were presented block-wise with six attacks per
      block. The fifth trial served as target trial where we presented identical
      attacks to control kinematic cues. We varied the outcomes of the preceding four
      attacks under three conditions: lobs only, smashes only or an alternating pattern
      of attack outcomes. In Exp. 1, skilled players but not novices were less accurate
      and responded later in target trials that were incongruent vs. congruent with
      preceding patterns. In Exp. 2, where the task was easier, another group of
      novices demonstrated a similar congruence effect for accuracy but not response
      time. Collectively, findings indicate that participants tended to preferentially
      expect the continuation of an attack pattern, while possibly attaching less
      importance to kinematic cues. Thus, overreliance on pattern continuation may be
      detrimental to anticipation in situations an action's outcome does not correspond
      to the pattern. From a methodological viewpoint, comparison of novices'
      performance in Exp. 1 and 2 suggests that task difficulty may be critical as to
      whether contextual cue effects can be identified in novices. 

PMID- 26310874
TI  - Resveratrol induces chemosensitization to 5-fluorouracil through up-regulation of
      intercellular junctions, Epithelial-to-mesenchymal transition and apoptosis in
      colorectal cancer.
AB  - 5-Fluorouracil (5-FU), a common chemotherapeutic agent used for the treatment of
      colorectal cancer (CRC), by itself has inadequate response rates; highlighting
      the need for novel and improved treatment regimens for these patients.
      Resveratrol, a naturally-occurring polyphenol, has been linked with
      chemosensitizing potential and anticancer properties; however, the underlying
      mechanisms for these effects remain poorly understood. The effect of resveratrol
      in parental CRC cell lines (HCT116, SW480) and their corresponding isogenic 5-FU
      chemoresistant derived clones (HCT116R, SW480R) was examined by MTT assays,
      intercellular junction formation and apoptosis by electron- and immunoelectron
      microscopy, nuclear factor-kappaB (NF-kappaB) and NF-kappaB regulated gene
      products by western blot analysis in a 3D-alginate microenvironment. Resveratrol
      blocked the proliferation of all four CRC cell lines and synergized the invasion
      inhibitory effects of 5-FU. Interestingly, resveratrol induced a transition from
      5-FU-induced formation of microvilli to a planar cell surface, which was
      concomitant with up-regulation of desmosomes, gap- and tight junctions (claudin
      2) and adhesion molecules (E-cadherin) expression in HCT116 and HCT116R cells.
      Further, resveratrol significantly attenuated drug resistance through inhibition
      of epithelial-mesenchymal transition (EMT) factors (decreased vimentin and slug,
      increased E-cadherin) and down-regulation of NF-kappaB activation and its
      translocation to the nucleus and abolished NF-kappaB-regulated gene end-products
      (MMP-9, caspase-3). Moreover, this suppression was mediated through inhibition of
      IkappaBalpha kinase and IkappaBalpha phosphorylation and degradation. Our results
      demonstrate that resveratrol can potentiate the anti-tumor effects of 5-FU on CRC
      cells by chemosensitizing them, inhibiting an EMT phenotype via up-regulation of
      intercellular junctions and by down-regulation of NF-kappaB pathway. 

PMID- 26310875
TI  - ABO Blood Type and Response of Activated Partial Thromboplastin Time to
      Dabigatran in Nonvalvular Atrial Fibrillation Patients.
AB  - BACKGROUND: The association between ABO blood type and the activated partial
      thromboplastin time (aPTT) under dabigatran therapy in nonvalvular atrial
      fibrillation (NVAF) patients is unclear. METHODS AND RESULTS: Between 2011 March
      and 2015 May, data on ABO blood type and aPTT under dabigatran were obtained for
      396 NVAF patients (baseline aPTT, 166). The prevalence of blood type O tended to
      increase or significantly increase according to baseline aPTT, aPTT under
      dabigatran, and their difference (?aPTT) (P=0.054, 0.001, and 0.012,
      respectively). CONCLUSIONS: In these NVAF patients, a high aPTT value under
      dabigatran therapy was associated with blood type O.

PMID- 26310876
TI  - Increased platelet inhibition after switching from maintenance clopidogrel to
      prasugrel in Japanese patients with stable coronary artery disease.
AB  - BACKGROUND: The pharmacodynamic effects of changing from standard-dose
      clopidogrel to low-dose (3.75 mg) prasugrel in Japanese patients are largely
      unknown. METHODS AND RESULTS: A total of 53 consecutive Japanese patients with
      stable coronary artery disease (CAD) who received aspirin and clopidogrel were
      enrolled. Clopidogrel was switched to 3.75 mg prasugrel. At day 14, prasugrel was
      switched to 75 mg clopidogrel. Platelet reactivity was measured using the
      VerifyNow assay at baseline, day 14, and day 28. VerifyNow P2Y12 reaction units
      (PRU) >208 was defined as high on-treatment platelet reactivity (HPR). The
      prevalence of HPR (18.9% vs. 41.5% vs. 44.2%, P<0.001) and the PRU level (154.3+/
      54.2 vs. 196.2+/-55.5 vs. 194.6+/-55.8, P<0.001) were significantly lower on
      prasugrel maintenance therapy compared with the clopidogrel therapy before and
      after switching. The CYP2C19 genotypes that account for the 3 phenotypes (ie,
      extensive metabolizer, intermediate metabolizer, and poor metabolizer) had a
      significant impact on platelet reactivity with clopidogrel (174.9+/-54.0 vs.
      193.1+/-56.5 vs. 240.6+/-25.4 PRU, P<0.001) but not prasugrel (147.0+/-51.9 vs.
      147.5+/-58.3 vs. 184.4+/-38.3 PRU, P=0.15). CONCLUSIONS: Low-dose prasugrel
      achieves stronger platelet inhibition than clopidogrel in Japanese patients with
      stable CAD.

PMID- 26310877
TI  - Predictors of smoking reduction outcomes in a sample of 287 patients with
      schizophrenia spectrum disorders.
AB  - Many studies have investigated whether a type of antipsychotics or type of
      adjuvant is associated with smoking reduction in patients with schizophrenia.
      However, there has been no study exploring a comprehensive range of factors
      related to smoking reduction in schizophrenia patients. We analyzed a dataset of
      287 smoking patients with schizophrenia who participated in an 8-week open-label
      study with high- (n = 90) or low-dose nicotine dermal patches (n = 132) or
      bupropion (n = 65). A logistic regression model and a linear mixed model were
      used to explore factors associated with the outcomes of smoking cessation and
      reduction, i.e., the number of cigarettes smoked and the level of nicotine
      dependence. The total cessation rate was 6.3 % (18/287). There were no
      significant predictors of cessation. The time effect of reduction was significant
      during the program (p = 0.001). Type of antipsychotics (p = 0.018), readiness to
      quit (p = 0.014), baseline number of cigarettes smoked per day (p = 0.001), and
      nicotine dependence level (p = 0.001) were significantly associated with smoking
      reduction. Patients on first-generation antipsychotics (n = 129) or clozapine (n
      = 70) reduced their smoking more than those on non-clozapine second-generation
      antipsychotics (n = 74). Patients in the preparation stage (n = 97) or in the
      contemplation (n = 70) reduced their smoking more than those in the
      precontemplation stage (n = 120). The mechanisms of tobacco addiction need to be
      better understood for further development of effective cessation programs in
      patients with schizophrenia.

PMID- 26310879
TI  - The Impact of Sexual Arousal on Sexual Risk-Taking and Decision-Making in Men and
      Women.
AB  - Sexual arousal has emerged as an important contextual feature in sexual
      encounters that can impact safer-sex decision-making. We conducted two
      experiments that investigated the effects of sexual arousal among male and female
      participants. Experiment 1 (N = 144) examined the impact of sexual around on
      sexual health decision-making. Sexually explicit and neutral video clips as well
      as hypothetical romantic scenarios were used to evaluate the effects of sexual
      arousal on sexual risk-taking intentions. Men and women who reported higher
      levels of sexual arousal also displayed greater intentions to participate in
      risky sexual behavior (e.g., unprotected sex with a new sex partner). Experiment
      2 (N = 122) examined the impact of sexual arousal on general risk-taking, using
      the same videos clips as in Experiment 1 and a modified version of a computerized
      Blackjack card game. Participants were offered a chance to make either a risky
      play or a safe play during ambiguous conditions. Increased sexual arousal in
      Experiment 2 was associated with impulsivity and a greater willingness to make
      risky plays in the Blackjack game. These findings suggest that, in situations
      where there are strong sexually visceral cues, both men and women experiencing
      strong sexual arousal may have lower inhibitions and may experience impaired
      decision-making. This phenomenon may have an impact during sexual encounters and
      may contribute to a failure to use appropriate prophylactic protection. 

PMID- 26310878
TI  - Depression, Compulsive Sexual Behavior, and Sexual Risk-Taking Among Urban Young
      Gay and Bisexual Men: The P18 Cohort Study.
AB  - Young gay, bisexual, and other men who have sex with men (YMSM) are at increased
      likelihood of experiencing depression and engaging in condomless sexual
      behaviors. The goal of the current investigation was to examine the relationship
      between negative mood and compulsive sexual behavior (CSB) and to assess for
      their individual and combined influence on sexual risk-taking behavior among a
      diverse sample of YMSM in New York City (the P18 Cohort Study). We first analyzed
      sociodemographic, depressive symptoms, CSB, and sexual risk-taking from the cross
      sectional data of 509, 18- or 19-year-old YMSM recruited using non-probability
      sampling. We found a significant positive correlation between CSB and depression
      and between CSB and frequency of condomless anal sex acts reported over the last
      30 days. Multivariate results found that the presence of both depression and CSB
      contributed to elevated sexual risk-taking among these urban YMSM. Clinical
      implications include the importance of assessing for CSB when depression is
      present and vice versa in order to improve HIV prevention. Informed by minority
      stress theory and syndemic theory, our results suggest that interventions focused
      on the health of YMSM recognize that mental health and social context all
      interact to increase physical health vulnerability vis-a-vis sexual behaviors,
      depression, and CSB. Thus, HIV prevention and intervention programs need to
      incorporate mental health components and services that address these needs.

PMID- 26310880
TI  - Effects of Experimenter Contact, Setting, Inquiry Mode, and Race on Women's Self
      Report of Sexual Attitudes and Behaviors: An Experimental Study.
AB  - Factors related to the research context, such as inquiry mode, setting, and
      experimenter contact, may affect participants' comfort with and willingness to
      disclose certain sexual attitudes or admit to engaging in sensitive sexual
      behaviors. In this study, 255 female undergraduates (42.7 % non-White) completed
      a survey containing measures of sexual behavior and attitudes. The level of
      experimenter contact (high vs. low contact), setting (in lab vs. out of lab), and
      inquiry mode (pencil-and-paper vs. computer) were manipulated and participants
      were randomly assigned to conditions. We hypothesized that low-contact, out-of
      lab, computer conditions would be associated with more liberal sexual attitudes
      and higher rates of reported sexual behaviors than high-contact, in-lab, and
      paper-and-pencil conditions, respectively. Further, we hypothesized that effects
      would be moderated by race, such that differences would be greater for non-White
      participants because of concerns that reporting socially undesirable behavior
      might fuel racial stereotypes. For attitudinal measures, White participants
      endorsed more liberal attitudes toward sex in high-contact conditions and non
      White participants endorsed more liberal attitudes in low-contact conditions. For
      behavioral measures, non-White participants reported more behaviors on pencil-and
      paper surveys than on computers. White participants demonstrated no significant
      mode-related differences or reported more sexual behaviors in computer conditions
      than paper-and-pencil conditions. Overall, results suggest that experimenter
      contact and mode significantly impact sexual self-report and this impact is often
      moderated by race.

PMID- 26310881
TI  - Highly robust transparent and conductive gas diffusion barriers based on tin
      oxide.
AB  - Transparent and electrically conductive gas diffusion barriers are reported. Tin
      oxide (SnOx ) thin films grown by atomic layer deposition afford extremely low
      water vapor transmission rates (WVTR) on the order of 10(-6) g (m(2) day)(-1) ,
      six orders of magnitude better than that established with ITO layers. The
      electrical conductivity of SnOx remains high under damp heat conditions (85 
      degrees C/85% relative humidity (RH)), while that of ZnO quickly degrades by more
      than five orders of magnitude. 

PMID- 26310883
TI  - Upscaling transport of a reacting solute through a peridocially converging
      diverging channel at pre-asymptotic times.
AB  - In this study we extend the Spatial Markov model, which has been successfully
      used to upscale conservative transport across a diverse range of porous media
      flows, to test if it can accurately upscale reactive transport, defined by a
      spatially heterogeneous first order degradation rate. We test the model in a well
      known highly simplified geometry, commonly considered as an idealized pore or
      fracture structure, a periodic channel with wavy boundaries. The edges of the
      flow domain have a layer through which there is no flow, but in which diffusion
      of a solute still occurs. Reactions are confined to this region. We demonstrate
      that the Spatial Markov model, an upscaled random walk model that enforces
      correlation between successive jumps, can reproduce breakthrough curves measured
      from microscale simulations that explicitly resolve all pertinent processes. We
      also demonstrate that a similar random walk model that does not enforce
      successive correlations is unable to reproduce all features of the measured
      breakthrough curves. 

PMID- 26310882
TI  - Risk of Nonspine Fractures in Older Adults with Sarcopenia, Low Bone Mass, or
      Both.
AB  - OBJECTIVES: To test the hypothesis that men and women with low bone mineral
      density (BMD) and sarcopenia have a higher risk of fracture than those with only
      one or neither conditions. DESIGN: The Osteoporotic Fractures in Men Study and
      the Study of Osteoporotic Fractures in women are prospective observational
      studies with a mean follow up of 9 (2000-2012) and 8 years (1997-2009),
      respectively. SETTING: U.S. clinical centers. PARTICIPANTS: Men (n = 5,544; mean
      age 73.7) and women (n = 1,114; mean age 77.6) aged 65 and older, able to walk
      without assistance, and without bilateral hip replacement. MEASUREMENTS:
      Sarcopenia was defined as low appendicular lean mass plus slowness or weakness
      and low BMD according to the World Health Organization definition of a T-score
      less than -1.0. Participants were classified as having normal BMD and no
      sarcopenia (3,367 men, 308 women), sarcopenia only (79 men, 48 women), low BMD
      only (1,986 men, 626 women), and low BMD and sarcopenia (112 men, 132 women).
      RESULTS: Men with low BMD and sarcopenia (hazard ratio (HR)=3.79, 95% confidence
      interval (CI)=2.65-5.41) and men with low BMD only (HR=1.67, 95% CI=1.45-1.93)
      but not men with sarcopenia only (HR=1.14, 95% CI=0.62-2.09) had greater risk of
      fracture than men with normal BMD and no sarcopenia. Women with low BMD and
      sarcopenia (HR=2.27, 95% CI=1.37-3.76) and women with low BMD alone (HR=2.62, 95%
      CI=1.74-3.95), but not women with only sarcopenia, had greater risk of fracture
      than women with normal BMD and no sarcopenia. CONCLUSION: Men with low BMD and
      sarcopenia are at especially high risk of fracture. Sarcopenia alone did not
      increase fracture risk in either group.

PMID- 26310884
TI  - Effects of virtual reality-based bilateral upper-extremity training on brain
      activity in post-stroke patients.
AB  - [Purpose] This study investigated the therapeutic effects of virtual reality
      based bilateral upper-extremity training on brain activity in patients with
      stroke. [Subjects and Methods] Eighteen chronic stroke patients were divided into
      two groups: the virtual reality-based bilateral upper-extremity training group (n
      = 10) and the bilateral upper-limb training group (n = 8). The virtual reality
      based bilateral upper-extremity training group performed bilateral upper
      extremity exercises in a virtual reality environment, while the bilateral upper
      limb training group performed only bilateral upper-extremity exercise. All
      training was conducted 30 minutes per day, three times per week for six weeks,
      followed by brain activity evaluation. [Results] Electroencephalography showed
      significant increases in concentration in the frontopolar 2 and frontal 4 areas,
      and significant increases in brain activity in the frontopolar 1 and frontal 3
      areas in the virtual reality-based bilateral upper-extremity training group.
      [Conclusion] Virtual reality-based bilateral upper-extremity training can improve
      the brain activity of stroke patients. Thus, virtual reality-based bilateral
      upper-extremity training is feasible and beneficial for improving brain
      activation in stroke patients. 

PMID- 26310885
TI  - Comparative evaluation of the antibacterial and physical properties of
      conventional glass ionomer cement containing chlorhexidine and antibiotics.
AB  - OBJECTIVE: To evaluate the antimicrobial efficacy and compressive strength of
      conventional glass ionomer cement (GIC) containing chlorhexidine and antibiotics
      at varying concentrations. MATERIALS AND METHODS: Chlorhexidine diacetate and
      antibiotics (ciprofloxacin, metronidazole, and minocycline) were incorporated
      into GIC Fuji IX at 1.5% and 3% w/w ratio to form the experimental groups. The
      experimental GIC specimens were placed on brain heart infusion agar plates
      inoculated with Streptococcus mutans, and the area of inhibition was measured
      after 48 h. The 24-h compressive strength of the set specimens was evaluated
      using a Universal Testing Machine. RESULTS: The control group demonstrated no
      zone of inhibition. All experimental groups showed inhibition against S. mutans
      (P < 0.05), with larger zones of inhibition found in the higher concentration
      groups. Compressive strength at the end of 24 h decreased in the experimental
      groups as compared to the control group (P < 0.05), but no difference was found
      between the experimental groups (P > 0.05). CONCLUSION: The present study
      demonstrated that experimental GICs containing chlorhexidine diacetate and
      antibiotics were effective in inhibiting S. mutans, and incorporation of 1.5% ABX
      was optimal to give the appropriate antibacterial and physical properties.

PMID- 26310886
TI  - The TFG-TEC oncoprotein induces transcriptional activation of the human beta
      enolase gene via chromatin modification of the promoter region.
AB  - Recurrent chromosome translocations are the hallmark of many human cancers. A
      proportion of human extraskeletal myxoid chondrosarcomas (EMCs) are associated
      with the characteristic chromosomal translocation t(3;9)(q11-12;q22), which
      results in the formation of a chimeric protein in which the N-terminal domain of
      the TRK-fused gene (TFG) is fused to the translocated in extraskeletal
      chondrosarcoma (TEC; also called CHN, CSMF, MINOR, NOR1, and NR4A3) gene. The
      oncogenic effect of this translocation may be due to the higher transactivation
      ability of the TFG-TEC chimeric protein; however, downstream target genes of TFG
      TEC have not yet been identified. The results presented here, demonstrate that
      TFG-TEC activates the human beta-enolase promoter. EMSAs, ChIP assays, and
      luciferase reporter assays revealed that TFG-TEC upregulates beta-enolase
      transcription by binding to two NGFI-B response element motifs located upstream
      of the putative transcription start site. In addition, northern blot,
      quantitative real-time PCR, and Western blot analyses showed that overexpression
      of TFG-TEC up-regulated beta-enolase mRNA and protein expression in cultured cell
      lines. Finally, ChIP analyses revealed that TFG-TEC controls the activity of the
      endogenous beta-enolase promoter by promoting histone H3 acetylation. Overall,
      the results presented here indicate that TFG-TEC triggers a regulatory gene
      hierarchy implicated in cancer cell metabolism. This finding may aid the
      development of new therapeutic strategies for the treatment of human EMCs. (c)
      2015 Wiley Periodicals, Inc.

PMID- 26310887
TI  - Tubulocystic renal cell carcinoma is an entity that is immunohistochemically and
      genetically distinct from papillary renal cell carcinoma.
AB  - AIMS: Some studies have suggested that tubulocystic carcinoma may be related to
      papillary renal cell carcinoma. We sought to compare and contrast the molecular
      and immunohistochemical profiles of tubulocystic carcinoma with those of
      papillary renal cell carcinoma. METHODS AND RESULTS: Twelve cases of pure
      tubulocystic renal cell carcinoma were subjected to fluorescence in-situ
      hybridization assessment of chromosomal number for chromosomes 7 and 17, and for
      TFE3 translocation. Immunohistochemical labelling for AMACR, p63, cytokeratin 7,
      PAX8, cytokeratin 20 and carbonic anhydrase IX was assessed in all tumours. No
      tumour showed gains of chromosomes 7 or 17, or TFE3 translocation by fluorescence
      in-situ hybridization. Immunohistochemistry revealed all tumours to be non
      reactive with antibodies against p63 and cytokeratin 20. Conversely, the antibody
      against AMACR gave a positive reaction in the neoplastic cells of all tumours.
      Four tumours showed focal labelling with antibody against carbonic anhydrase IX,
      and five tumours showed focally positive reactions with antibody against
      cytokeratin 7. Recurrence and metastatic disease were not found for the patients
      with available follow-up information. CONCLUSIONS: Pure tubulocystic renal cell
      carcinoma is an indolent tumour with a good prognosis. Our data support the
      distinction of this neoplasm as a separate entity.

PMID- 26310888
TI  - Serum albumin and muscle measures in a cohort of healthy young and old
      participants.
AB  - Consensus on clinically valid diagnostic criteria for sarcopenia requires a
      systematical assessment of the association of its candidate measures of muscle
      mass, muscle strength, and physical performance on one side and muscle-related
      clinical parameters on the other side. In this study, we systematically assessed
      associations between serum albumin as a muscle-related parameter and muscle
      measures in 172 healthy young (aged 18-30 years) and 271 old participants (aged
      69-81 year) from the European MYOAGE study. Muscle measures included relative
      muscle mass, i.e., total- and appendicular lean mass (ALM) percentage, absolute
      muscle mass, i.e., ALM/height(2) and total lean mass in kilograms, handgrip
      strength, and walking speed. Muscle measures were standardized and analyzed in
      multivariate linear regression models, stratified by age. Adjustment models
      included age, body composition, C-reactive protein and lifestyle factors. In
      young participants, serum albumin was positively associated with lean mass
      percentage (p = 0.007) and with ALM percentage (p = 0.001). In old participants,
      serum albumin was not associated with any of the muscle measures. In conclusion,
      the association between serum albumin and muscle measures was only found in
      healthy young participants and the strongest for measures of relative muscle
      mass.

PMID- 26310889
TI  - Safety and efficacy of combination therapy with low-dose gemcitabine, paclitaxel,
      and sorafenib in patients with cisplatin-resistant urothelial cancer.
AB  - Various regimens including molecular targeted agents have been examined in
      patients with cisplatin (CDDP)-resistant urothelial cancer (UC). However, some
      studies have been stopped owing to the development of severe adverse events. The
      main aim of this study was to examine the anticancer effects, changes in the
      quality of life (QoL), and safety of combined therapy of low-dose gemcitabine,
      paclitaxel, and sorafenib (LD-GPS) in patients with CDDP-resistant UC. Twenty
      patients were treated with gemcitabine (700 mg/m(2) on day 1), paclitaxel (70
      mg/m(2) on day 1), and sorafenib (400 mg/day on days 8-22). QoL and pain relief
      were evaluated using the short-form survey (SF)-36 for bodily pain and the visual
      analog scale (VAS). VAS scores were significantly decreased by both the second-
      and third-line therapies (P = 0.012 and 0.028, respectively). The bodily pain
      score from the SF-36 survey was also significantly (P = 0.012) decreased.
      Complete responses, partial responses, and stable disease were found in 0 (0.0
      %), 1 (5.0 %), and 13 patients (65 %), respectively. The median (interquartile
      range) period of overall survival after starting of this therapy was 7 (5-11)
      months. Three patients (15.0 %) stopped therapy because of grade 3 fatigue and
      hand-foot reactions. LD-GPS therapy was well tolerated by patients with CDDP
      resistant UC. QoL was maintained, and improvements in their pain levels were
      found after treatment; pain relief was detected after third-line therapy. We
      suggest that this treatment regimen is worthy of consideration as second- and
      third-line therapy for patients with CDDP-resistant UC. 

PMID- 26310890
TI  - Structure-activity study of quinazoline derivatives leading to the discovery of
      potent EGFR-T790M inhibitors.
AB  - We have developed a series of 6, 7-disubstituted-4-(arylamino) quinazoline
      derivatives that functioned as irreversible EGFR inhibitors, and these compounds
      exhibited excellent enzyme inhibition potency. As compared with afatinib, some of
      them showed significantly enhanced activities towards H1975 cells (EGFR-T790M).
      Furthermore, the optimized compounds 7q and 8f also demonstrated good
      pharmacokinetic profiles, oral bioavailability as well as excellent in vivo
      efficacy in H1975 and HCC827 xenografts at a non-toxic dose. Based on the
      improved safety and efficacy against EGFR-T790M resistance, 7q and 8f are
      promising candidates for further studies.

PMID- 26310891
TI  - Discovery of indole-based tetraarylimidazoles as potent inhibitors of urease with
      low antilipoxygenase activity.
AB  - A series of tetraarylimidazoles (5A-5O) were prepared by one pot four component
      condensation reactions of 2-arylindole-3-carbaldehydes, substituted anilines,
      benzil and ammonium acetate in acetic acid. The synthesized compounds exhibited
      potent antiurease activity with IC50 values ranging from 0.12 +/- 0.06 MUM to
      29.12 +/- 0.18 MUM as compared with thiourea. However, low inhibition profiles
      were observed for lipoxygenase. The data show that tetraarylimidazoles containing
      a substituted 2-penylindole have emerged as a new class of potent inhibitors of
      urease enzyme.

PMID- 26310892
TI  - Design, synthesis, and structure-activity relationship studies of novel
      thienopyrrolidone derivatives with strong antifungal activity against Aspergillus
      fumigates.
AB  - In order to further enhance the anti-Aspergillus efficacy of our previously
      discovered antifungal lead compounds (I), two series of novel azoles featuring
      thieno[2,3-c]pyrrolidone and thieno[3,2-c]pyrrolidone nuclei were designed and
      evaluated for their in vitro activity on the basis of the binding mode of
      albaconazole using molecular docking, along with SARs of antifungal triazoles.
      Most of target compounds exhibited excellent activity against Candida and
      Cryptococcus spp., with MIC values in the range of 0.0625 MUg/ml to 0.0156
      MUg/ml. The thieno[3,2-c]pyrrolidone unit was more suited for improving activity
      against Aspergillus spp. The most potent compound, 18a, was selected for further
      development due to its significant in vitro activity against Aspergillus spp.
      (MIC = 0.25 MUg/ml), as well as its high metabolic stability in human liver
      microsomes.

PMID- 26310893
TI  - Synthesis and inhibitory effects of novel pyrimido-pyrrolo-quinoxalinedione
      analogues targeting nucleoproteins of influenza A virus H1N1.
AB  - The influenza nucleoprotein (NP) is a single-strand RNA-binding protein and the
      core of the influenza ribonucleoprotein (RNP) particle that serves many critical
      functions for influenza replication. NP has been considered as a promising anti
      influenza target. A new class of anti-influenza compounds, nucleozin and
      analogues were reported recently in several laboratories to inhibit the synthesis
      of influenza macromolecules and prevent the cytoplasmic trafficking of the
      influenza RNP. In this study, pyrimido-pyrrolo-quinoxalinedione (PPQ) analogues
      as a new class of novel anti-influenza agents are reported. Compound PPQ-581 was
      identified as a potential anti-influenza lead with EC50 value of 1 MUM for
      preventing virus-induced cytopathic effects. PPQ produces similar anti-influenza
      effects as nucleozin does in influenza-infected cells. Treatment with PPQ at the
      beginning of H1N1 infection inhibited viral protein synthesis, while treatment at
      later times blocked the RNP nuclear export and the appearance of cytoplasmic RNP
      aggregation. PPQ resistant H1N1 (WSN) viruses were isolated and found to have a
      NPS377G mutation. Recombinant WSN carrying the S377G NP is resistant to PPQ in
      anti-influenza and RNA polymerase assays. The WSN virus with the NPS377G mutation
      also is devoid of the PPQ-mediated RNP nuclear retention and cytoplasmic
      aggregation. The NPS377G expressing WSN virus is not resistant to the reported NP
      inhibitors nucleozin. Similarly, the nucleozin resistant WSN viruses are not
      resistant to PPQ, suggesting that PPQ targets a different site from the nucleozin
      binding site. Our results also suggest that NP can be targeted through various
      binding sites to interrupt the crucial RNP trafficking, resulting in influenza
      replication inhibition.

PMID- 26310894
TI  - Piperazine scaffold: A remarkable tool in generation of diverse pharmacological
      agents.
AB  - Piperazine is one of the most sought heterocyclics for the development of new
      drug candidates. This ring can be traced in a number of well established,
      commercially available drugs. Wide array of pharmacological activities exhibited
      by piperazine derivatives have made them indispensable anchors for the
      development of novel therapeutic agents. The review herein highlights the
      therapeutic significance of piperazine derivatives. Various therapeutically
      active piperazine derivatives developed by several chemists are reported here. 

PMID- 26310895
TI  - Quinazolinedione SIRT6 inhibitors sensitize cancer cells to chemotherapeutics.
AB  - The NAD(+)-dependent sirtuin SIRT6 is highly expressed in human breast, prostate,
      and skin cancer where it mediates resistance to cytotoxic agents and prevents
      differentiation. Thus, SIRT6 is an attractive target for the development of new
      anticancer agents to be used alone or in combination with chemo- or radiotherapy.
      Here we report on the identification of novel quinazolinedione compounds with
      inhibitory activity on SIRT6. As predicted based on SIRT6's biological functions,
      the identified new SIRT6 inhibitors increase histone H3 lysine 9 acetylation,
      reduce TNF-alpha production and increase glucose uptake in cultured cells. In
      addition, these compounds exacerbate DNA damage and cell death in response to the
      PARP inhibitor olaparib in BRCA2-deficient Capan-1 cells and cooperate with
      gemcitabine to the killing of pancreatic cancer cells. In conclusion, new SIRT6
      inhibitors with a quinazolinedione-based structure have been identified which are
      active in cells and could potentially find applications in cancer treatment.

PMID- 26310896
TI  - Role of substituents in cyclodextrin derivatives for enantioselective gas
      chromatographic separation of chiral terpenoids in the essential oils of Mentha
      spicata.
AB  - Enantioselective GC-FID and enantioselective GC-MS have been utilized under
      temperature gradient mode with differently substituted heptakis- and octakis
      cyclodextrins to achieve the resolution of chiral terpenoids in the essential oil
      of indigenously grown cultivars of Mentha spicata. Modified cyclodextrins were
      derivatized in GC column for the separation of chiral terpenoids. A 2,3-diethyl-6
      tert-butyldimethylsilyl-beta-cyclodextrin doped into 14%
      cyanopropylphenyl/86%dimethylpolysiloxane (TBDE-beta-CD) showed good
      enantioselectivity for all the studied chiral compounds excluding carvone.
      Carvone enantiomers were well resolved in 2,3-diacetoxy-6-tert-butyldimethylsilyl
      beta-cyclodextrin column (TBDA-beta-CD) with enantioseparation (Es) of 1.006. A
      TBDE-beta-CD provides maximum enantiomeric separation for beta-pinene (Es 1.038),
      sabinene (Es 1.051), limonene (Es 1.045), isomenthone (Es 1.029) and alpha
      terpineol (Es 1.014). Furthermore, enantiomer elution order reversal was observed
      for sabinene, menthone, terpinen-4-ol and menthol while changing from beta- to
      gamma-cyclodextrin phase. Carvone exhibits enantiomer elution order reversal by
      changing substituents i.e., methyl to acetyl at 2- & 3- position of the
      cyclodextrin derivative. Chiral constituents such as (+)-isomenthone, (-)
      menthone, (1R,2S,5R)-(-)-menthol and (4S)-(+)-piperitone exist as a single
      enantiomer with >99% excess. Existence of (R)-(+)-limonene and (S)-(+)-carvone
      enantiomers has been proven first time in M. spicata essential oils and can be
      used as the marker for Indian origin. 

PMID- 26310897
TI  - Quantitative bioanalysis of antibody-conjugated payload in monkey plasma using a
      hybrid immuno-capture LC-MS/MS approach: Assay development, validation, and a
      case study.
AB  - Antibody drug conjugates (ADCs) are complex molecules composed of two
      pharmacologically distinct components, the cytotoxic payload and the antibody.
      The measurement of the payload molecules that are attached to the antibody in
      vivo is important for the evaluation of the safety and efficacy of ADCs, and can
      also provide distinct information compared to the antibody-related analytes.
      However, analyzing the antibody-conjugated payload is challenging and in some
      cases may not be feasible. The in vivo change in drug antibody ratio (DAR), due
      to deconjugation, biotransformation or other clearance phenomena, generates
      unique and additional challenges for ADC analysis in biological samples. Here, we
      report a novel hybrid approach with immuno-capture of the ADC, payload cleavage
      by specific enzyme, and LC-MS/MS of the cleaved payload to quantitatively measure
      the concentration of payload molecules still attached to the antibody via linker
      in plasma. The ADC reference material used for the calibration curve is not
      likely to be identical to the ADC measured in study samples due to the change in
      DAR distribution over the PK time course. The assay clearly demonstrated that
      there was no bias in the measurement of antibody-conjugated payload for ADC with
      varying DAR, which thus allowed accurate quantification even when the DAR
      distribution dynamically changes in vivo. This hybrid assay was fully validated
      based on a combination of requirements for both chromatographic and ligand
      binding methods, and was successfully applied to support a GLP safety study in
      monkeys. 

PMID- 26310898
TI  - Validation of an assay for quantification of free normetanephrine, metanephrine
      and methoxytyramine in plasma by high performance liquid chromatography with
      coulometric detection: Comparison of peak-area vs. peak-height measurements.
AB  - BACKGROUND: Measurements of plasma concentrations of free normetanephrine (NMN),
      metanephrine (MN) and methoxytyramine (MTY) constitute the most diagnostically
      accurate screening test for pheochromocytomas and paragangliomas. The aim of this
      article is to present the results from a validation of an analytical method
      utilizing high performance liquid chromatography with coulometric detection (HPLC
      CD) for quantifying plasma free NMN, MN and MTY. Additionally, peak integration
      by height and area and the use of one calibration curve for all batches or
      individual calibration curve for each batch of samples was explored as to
      determine the optimal approach with regard to accuracy and precision. METHODS:
      The method was validated using charcoal stripped plasma spiked with solutions of
      NMN, MN, MTY and internal standard (4-hydroxy-3-methoxybenzylamine) with the
      exception of selectivity which was evaluated by analysis of real plasma samples.
      Calibration curve performance, accuracy, precision and recovery were determined
      following both peak-area and peak-height measurements and the obtained results
      were compared. The most accurate and precise method of calibration was evaluated
      by analyzing quality control samples at three concentration levels in 30
      analytical runs. RESULTS: The detector response was linear over the entire tested
      concentration range from 10 to 2000pg/mL with R(2)>=0.9988. The LLOQ was 10pg/mL
      for each analyte of interest. To improve accuracy for measurements at low
      concentrations, a weighted (1/amount) linear regression model was employed, which
      resulted in inaccuracies of -2.48 to 9.78% and 0.22 to 7.81% following peak-area
      and peak-height integration, respectively. The imprecisions ranged from 1.07 to
      15.45% and from 0.70 to 11.65% for peak-area and peak-height measurements,
      respectively. The optimal approach to calibration was the one utilizing an
      individual calibration curve for each batch of samples and peak-height
      measurements. It was characterized by inaccuracies ranging from -3.39 to +3.27%
      and imprecisions from 2.17 to 13.57%. CONCLUSIONS: The established HPLC-CD method
      enables accurate and precise measurements of plasma free NMN, MN and MTY with
      reasonable selectivity. Preparing calibration curve based on peak-height
      measurements for each batch of samples yields optimal accuracy and precision.

PMID- 26310899
TI  - The Role of MicroRNAs in the Chemoresistance of Breast Cancer.
AB  - Preclinical Research Breast cancer is the most prevalent malignancy in women with
      more than 1.3 million new cases every year worldwide. Chemotherapy is a critical
      therapeutic strategy for breast cancer, while chemoresistance remains a major
      obstacle to treatment success. In the past two decades, significant progress has
      been achieved in understanding drug resistance in breast cancer, involving drug
      efflux, alterations in DNA repair pathways, suppression of apoptosis as well as
      epithelial-mesenchymal transition, and cancer stem cells. However, more effective
      therapeutic targets and novel biomarkers are still urgently needed to improve the
      overall survival and refine the therapeutic strategy for breast cancer patients.
      MicroRNAs (miRNAs) play crucial roles in cellular processes, such as cell
      differentiation, proliferation, and apoptosis. The recent discovery of miRNAs in
      malignancy has provided new directions for research on mechanisms underlying
      response to chemotherapy. Furthermore, several studies have documented that
      selected miRNAs, such as miR-200c and miR-34a, may influence response to
      chemotherapy in several tumor types, including breast cancer. The use of miRNAs
      as therapeutic targets to overcome chemoresistance is currently under
      investigation. In this review, we summarize the roles of miRNAs in
      chemoresistance through multiple molecular mechanisms, and highlight the
      potential diagnostic and therapeutic applications of miRNAs in overcoming breast
      cancer chemoresistance.

PMID- 26310900
TI  - Comparison of Loading Efficiency between Hyperbranched Polymers and Cross-Linked
      Nanogels at Various Branching Densities.
AB  - The effect of branching point structures and densities is studied between azido
      containing hyperbranched polymers and cross-linked nanogels on their loading
      efficiency of alkynyl-containing dendron molecules. Hyperbranched polymers that
      contained "T"-shaped branching linkage from which three chains radiated out and
      cross-linked nanogels that contained "X"-shaped branching linkage with four
      radiating chains are synthesized in microemulsion using either atom transfer
      radical polymerization (ATRP) or conventional radical polymerization (RP)
      technique. Both polymers have similar density of azido groups in the structure
      and exhibit similar hydrodynamic diameter in latexes before purification.
      Subsequent copper-catalyzed azide-alkyne cycloaddition reactions between these
      polymers and alkynyl-containing dendrons in various sizes (G1-G3) demonstrate an
      order of dendron loading efficiencies (i.e., final conversion of alkynyl
      containing dendron) as hyperbranched polymers > nanogels synthesized by ATRP >
      nanogels synthesized by RP. Decreasing the branching density or using smaller
      dendron molecules increases the click efficiency of both polymers. When G2
      dendrons with a molecular weight of 627 Da are used to click with the
      hyperbranched polymers composed of 100% inimer, a maximum loading efficiency of
      G2 in the loaded hyperbranched polymer is 58% of G2 by weight. These results
      represent the first comparison between hyperbranched polymers and cross-linked
      nanogels to explore the effect of branching structures on their loading
      efficiencies. 

PMID- 26310901
TI  - The effect of pars plana vitrectomy and nuclear cataract on oxygen saturation in
      retinal vessels, diabetic and non-diabetic patients compared.
AB  - PURPOSE: To determine the effect of pars plana vitrectomy (PPV) on oxygen
      saturation in retinal vessels in patients with diabetes and non-diabetes after a
      1-year follow-up. METHODS: This was a prospective consecutive interventional case
      series in 82 eyes in 82 patients. The sample consisted of 25 patients with non
      proliferative diabetic retinopathy with macular oedema based on vitreoretinal
      traction or epiretinal membrane (ERM) and 57 non-diabetic patients with macular
      hole and ERM. Automatic retinal oximetry (Oxymap Inc.) was used on all patients
      24 hr prior to PPV, and it was also used 7 and 52 weeks after PPV (classic 20G or
      sutureless 23G). We analysed the data according to subgroup diagnosis and lens
      status. RESULTS: Arterial saturation increased significantly from 96.4 +/- 2.9%
      at baseline to 96.6 +/- 3.4% at week 7 and 97.3 +/- 3.4% at week 52 (p < 0.0001;
      Friedman test). Vein saturation also increased significantly from 63.5 +/- 7.9%
      at baseline to 66.1 +/- 7.7% and 67.0 +/- 7.2% at weeks 7 and 52 (p < 0.0001;
      Friedman test). The value of the arteriovenous (A-V) difference decreased
      significantly after vitrectomy from 32.8 +/- 7.5% at baseline to 30.5 +/- 7.5%
      and 30.3 +/- 7.0% at weeks 7 and 52 (p < 0.0001; Friedman test). The subgroup
      analysis revealed that in patients with diabetes, there were no statistically
      significant changes in oxygen saturation in blood vessels or in the A-V
      difference after PPV. After vitrectomy, retinal vessel diameter reduced by about
      3.5% in both groups of patients. Further, the analysis revealed that
      opacification of the lens leads to a decrease in oxygen saturation in contrast to
      a clear lens and pseudophakic IOLs. CONCLUSION: Oxygen saturation is higher in
      the retinal veins and arteries after PPV in patients with non-diabetes, and this
      lasts for at least 52 weeks. In contrast, in patients with diabetes, there is no
      increase in oxygen saturation in the retinal vessels after vitrectomy. After
      vitrectomy, retinal vessel diameter reduced in both groups of patients. Further,
      the nuclear cataract progression has substantial effect on oximetry results.
      Patients with nuclear cataract exhibited an increase in saturation in both
      arteries and veins, but the A-V difference remained the same.

PMID- 26310902
TI  - Captive Care, Raising, and Breeding of the Veiled Chameleon (Chamaeleo
      calyptratus).
AB  - Squamate reptiles comprise approximately one-third of all living amniotes. In
      most of these species, it is difficult to study gastrulation and neurulation
      because the embryos are at a late stage of development at the time of
      oviposition. This is not the case, however, in veiled chameleons (Chamaeleo
      calyptratus), which are increasingly being used as a model organism to study
      these and other developmental and evolutionary phenomena. Originating from the
      Arabian Peninsula, veiled chameleons are arboreal specialists that possess
      extensive morphological specializations for climbing. They naturally inhabit
      semitropical habitats, but they also have an almost 30-yr history of being bred
      in captivity. Veiled chameleons breed readily and do not require a period of
      cooling to induce the reproductive cycle, and females can produce ~45-90 eggs
      multiple times per year. Thus, compared with other reptiles, relatively few
      animals are needed to maintain a productive breeding colony. Herein, we present
      the conditions, equipment, and techniques required for proper husbandry and
      breeding of veiled chameleons within a laboratory environment. 

PMID- 26310903
TI  - The Veiled Chameleon (Chamaeleo calyptratus Dumeril and Dumeril 1851): A Model
      for Studying Reptile Body Plan Development and Evolution.
AB  - Vertebrate model organisms have facilitated the discovery and exploration of
      morphogenetic events and developmental pathways that underpin normal and
      pathological embryological events. In contrast to amniotes such as Mus musculus
      (Mammalia) and Gallus gallus (Aves), our understanding of early patterning and
      developmental events in reptiles (particularly nonavians) remains weak. Squamate
      reptiles (lizards, snakes, and amphisbaenians) comprise approximately one-third
      of all living amniotes. But studies of early squamate development have been
      limited because, in most members of this lineage, embryo development at the time
      of oviposition is very advanced (limb bud stages and older). In many cases,
      squamates give birth to fully developed offspring. However, in the veiled
      chameleon (Chamaeleo calyptratus), embryos have progressed only to a primitive
      pregastrula stage at the time of oviposition. Furthermore, the body plan of the
      veiled chameleon is highly specialized for climbing in an arboreal environment.
      It possesses an entire suite of skeletal and soft anatomical modifications,
      including cranioskeletal ornamentation, lingual anatomy and biomechanics for
      projection, autopodial clefting for grasping, adaptations for rapid integumental
      color changes, a prehensile tail with a lack of caudal autotomy, the loss of the
      tympanum in the middle ear, and the acquisition of turreted eyes. Thus, C.
      calyptratus is an important model organism for studying the role of ecological
      niche specialization, as well as genetic and morphological evolution within an
      adaptive framework. More importantly, this species is easily bred in captivity,
      with only a small colony (<10 individuals) needed to obtain hundreds of embryos
      every year. 

PMID- 26310904
TI  - Sb Nanoparticles Encapsulated in a Reticular Amorphous Carbon Network for
      Enhanced Sodium Storage.
AB  - Sb nanoparticles encapsulated in 3D reticular carbon network (denoted Sb@3D RCN)
      film are prepared by the electrostatic spray deposition technique followed by a
      heat treatment. When used as a binder-free anode for a Na-ion battery, it shows
      excellent long-life cyclability. The unique reticular, porous, and core-shell
      structure of Sb@3D RCN contributes significantly to the excellent sodium storage
      performance. 

PMID- 26310905
TI  - A Bio-Inspired, Catalytic E -> Z Isomerization of Activated Olefins.
AB  - Herein, Nature's flavin-mediated activation of complex (poly)enes has been
      translated to a small molecule paradigm culminating in a highly (Z)-selective,
      catalytic isomerization of activated olefins using (-)-riboflavin (up to 99:1
      Z/E). In contrast to the prominent Z -> E isomerization of the natural system, it
      was possible to invert the directionality of the isomerization (E -> Z) by
      simultaneously truncating the retinal scaffold, and introducing a third olefin
      substituent to augment A1,3-strain upon isomerization. Consequently, conjugation
      is reduced in the product chromophore leading to a substrate/product combination
      with discrete photophysical signatures. The operationally simple isomerization
      protocol has been applied to a variety of enone-derived substrates and showcased
      in the preparation of the medically relevant 4-substituted coumarin scaffold. A
      correlation of sensitizer triplet energy (ET) and reaction efficiency, together
      with the study of additive effects and mechanistic probes, is consistent with a
      triplet energy transfer mechanism. 

PMID- 26310906
TI  - Regulation of autophagy by coordinated action of mTORC1 and protein phosphatase
      2A.
AB  - Autophagy is a cellular catabolic process critical for cell viability and
      homoeostasis. Inhibition of mammalian target of rapamycin (mTOR) complex-1
      (mTORC1) activates autophagy. A puzzling observation is that amino acid
      starvation triggers more rapid autophagy than pharmacological inhibition of
      mTORC1, although they both block mTORC1 activity with similar kinetics. Here we
      find that in addition to mTORC1 inactivation, starvation also causes an increase
      in phosphatase activity towards ULK1, an mTORC1 substrate whose dephosphorylation
      is required for autophagy induction. We identify the starvation-stimulated
      phosphatase for ULK1 as the PP2A-B55alpha complex. Treatment of cells with
      starvation but not mTORC1 inhibitors triggers dissociation of PP2A from its
      inhibitor Alpha4. Furthermore, pancreatic ductal adenocarcinoma cells, whose
      growth depends on high basal autophagy, possess stronger basal phosphatase
      activity towards ULK1 and require ULK1 for sustained anchorage-independent
      growth. Taken together, concurrent mTORC1 inactivation and PP2A-B55alpha
      stimulation fuel ULK1-dependent autophagy. 

PMID- 26310907
TI  - Efficacy and safety of bio-chemotherapy with dacarbazine plus interleukin-2 in
      patients with unresectable malignant melanoma.
AB  - AIM: This study retrospectively evaluated the toxicity and efficacy of
      dacarbazine (DTIC) with low-dose subcutaneous interleukin-2 (IL-2) for patients
      with advanced melanoma. METHOD: Patients with unresectable malignant melanoma
      received bio-chemotherapy DTIC (330 mg/m(2) , every 3 weeks ) and IL-2 18 MIU
      (million international units) in divided doses by subcutaneous injection three
      times a week for 4 weeks. Treatment was performed for six cycles or until disease
      progression or unbearable toxicity. RESULTS: From October 2006 to November 2013,
      up to 31 patients (17 men; 14 women) were enrolled. Their median age was 48 years
      (range, 22-81 years). Subtypes of melanoma included 11 (35.4%) acral lentiginous,
      nodular, 1 (3.2%) superficial spreading, 10 (32.2%) mucosal and 5 (16.1%) others.
      The response rate was 19.3%, including 3.2% with a complete response, 16.1% with
      a partial response and 6.3% with stable disease. The median progression-free
      survival time was 3.5 months (95% CI: 3.0-3.9 months). The median overall
      survival time was 8.6 months (95% CI: 4.1-10.9 months). The 1-year survival rate
      was 39% and the 5-year survival rate was 10%. CONCLUSIONS: Our data demonstrated
      that low-dose subcutaneous IL-2 plus DTIC has modest efficacy and may produce
      long-term survival in small proportion of patients. Furthermore, the treatment is
      well tolerated by patients.

PMID- 26310909
TI  - Feasibility of Contralateral Oblique Fluoroscopy-guided Cervical Interlaminar
      Steroid Injections.
AB  - BACKGROUND: Cervical epidural steroid injection (CESI), given in conjunction with
      local anesthetics, is a common remedy for cervical radicular pain and is
      generally performed under c-arm fluoroscopic guidance, computed tomography (CT),
      or ultrasound. Interlaminar procedures, such as CESI, typically rely on
      anteroposterior and lateral (APL) views during needle placement. However, lateral
      views may be obscured by body habitus in certain individuals. Swimmer's view or
      contralateral oblique (CLO) view may be used to avoid this. OBJECTIVE: Our intent
      was to assess technical success and procedural risk in patients subjected to
      image-guided CESI procedures with CLO c-arm fluoroscopy. METHODS: A total of 186
      of patients were enrolled and randomly assigned to 1 of 3 groups undergoing image
      guided CESI via (1) CT, (2) c-arm fluoroscopy CLO, and (3) c-arm fluoroscopy APL.
      Complication rates and technical success were assessed, basing the latter on
      image reviews to confirm the presence of epidural contrast. RESULTS: All image
      guided CESI procedures utilizing CT and CLO fluoroscopy proved technically
      successful. In the CT group, epidural needle tip and contrast dispersion were
      clearly visible at all levels of study. In the CLO subset, needle tip visibility
      was unclear in isolated instances at levels C6-7 and C7-T1 (1 patient each
      level). In APL procedures, needle tip was regularly obscured by shoulder anatomy
      at levels C6-7 (26 of 41 patients) and C7-T1 (15 of 16 patients), and contrast
      dispersion was often uncertain. CONCLUSION: CLO fluoroscopy-guided CESI is
      feasible and safe, comparing favorably with CT-guided CESI.

PMID- 26310908
TI  - Strategies for combining immunotherapy with radiation for anticancer therapy.
AB  - Radiation therapy controls local disease but also prompts the release of tumor
      associated antigens and stress-related danger signals that primes T cells to
      promote tumor regression at unirradiated sites known as the abscopal effect. This
      may be enhanced by blocking inhibitory immune signals that modulate immune
      activity through a variety of mechanisms. Indeed, abscopal responses have
      occurred in patients with lung cancer or melanoma when given anti-CTLA4 antibody
      and radiation. Other approaches involve expanding and reinfusing T or NK cells or
      engineered T cells to express receptors that target specific tumor peptides.
      These approaches may be useful for immunocompromised patients receiving
      radiation. Preclinical and clinical studies are testing both immune checkpoint
      based strategies and adoptive immunotherapies with radiation. 

PMID- 26310910
TI  - The substrate matters in the Raman spectroscopy analysis of cells.
AB  - Raman spectroscopy is a powerful analytical method that allows deposited and/or
      immobilized cells to be evaluated without complex sample preparation or labeling.
      However, a main limitation of Raman spectroscopy in cell analysis is the
      extremely weak Raman intensity that results in low signal to noise ratios.
      Therefore, it is important to seize any opportunity that increases the intensity
      of the Raman signal and to understand whether and how the signal enhancement
      changes with respect to the substrate used. Our experimental results show clear
      differences in the spectroscopic response from cells on different surfaces. This
      result is partly due to the difference in spatial distribution of electric field
      at the substrate/cell interface as shown by numerical simulations. We found that
      the substrate also changes the spatial location of maximum field enhancement
      around the cells. Moreover, beyond conventional flat surfaces, we introduce an
      efficient nanostructured silver substrate that largely enhances the Raman signal
      intensity from a single yeast cell. This work contributes to the field of
      vibrational spectroscopy analysis by providing a fresh look at the significance
      of the substrate for Raman investigations in cell research. 

PMID- 26310911
TI  - FABP4 reversed the regulation of leptin on mitochondrial fatty acid oxidation in
      mice adipocytes.
AB  - Fatty acid binding protein 4 (FABP4), plays key role in fatty acid transportation
      and oxidation, and increases with leptin synergistically during adipose
      inflammation process. However, the regulation mechanism between FABP4 and leptin
      on mitochondrial fatty acid oxidation remains unclear. In this study, we found
      that FABP4 reduced the expression of leptin, CPT-1 and AOX1 in mice adipocytes.
      Conversely, FABP4 was down-regulated in a time-dependent manner by leptin
      treatment. Additionally, forced expression of FABP4 attenuated the expression of
      PGC1-alpha, UCP2, CPT-1, AOX1 and COX2 compared with leptin incubation. Moreover,
      mitochondrial membrane potential, fatty acid oxidation enzyme medium-chain acyl
      CoA dehydrogenase (MCAD), long-chain acyl-CoA dehydrogenase (LCAD) and Cyt C
      levels were reduced in response to the overexpression of FABP4. These reductions
      correspond well with the reduced release of free fatty acid and the inactivation
      of mitochondrial complexes I and III by FABP4 overexpression. Furthermore,
      addition of the Akt/mTOR pathway-specific inhibitor (MK2206) blocked the
      mitochondrial fatty acid oxidation and respiration factors, whereas interference
      of FABP4 overcame these effects. Taken together, FABP4 could reverse the
      activation of the leptin-induced mitochondrial fatty acid oxidation, and the
      inhibition of Akt/mTOR signal pathway played a key role in this process. 

PMID- 26310912
TI  - Willingness of reproductive-aged women in a Nigerian community to accept human
      papillomavirus vaccination for their children.
AB  - AIM: The aim of this study was to determine the willingness of reproductive-aged
      women in a Nigerian community to allow human papillomavirus (HPV) vaccination in
      their children and the associated factors with this decision. MATERIAL AND
      METHODS: A multistage household survey of 1002 women who participated in the HPV
      Vaccine and Cervical Cancer Prevention Survey from 26 August to 29 September 2012
      at Ibadan North Local Government Area, Mokola Ibadan, Nigeria. Descriptive,
      bivariate and multivariable analyses were performed, and statistical significance
      was set at 95% confidence level (CI). RESULTS: There was high willingness (88.6%)
      to vaccinate, and this attitude was associated with previous history of genital
      discharge or sores (adjusted odds ratio, 1.91; 95%CI, 1.05-3.45), and knowledge
      that cervical cancer is preventable (adjusted odds ratio, 1.67; 95%CI, 1.07
      2.59). On the likely acceptability of Nigerian HPV vaccine policy, about two
      thirds strongly agreed to its incorporation into the routine immunization program
      (66.9%), it being free (66.7%) and mandatory (64.3%), amongst other factors. The
      commonest concerns raised were cost/expenses (10.2%), that it might encourage
      promiscuity (9.9%), or stimulate early sexual debut (6.7%), and fear of
      infertility (6.3%). CONCLUSION: This study found that the majority of Nigerian
      women are willing to vaccinate their children against HPV infection and would
      prefer free universal HPV vaccination with regulation to ensure better uptake.
      The concerns expressed would need to be addressed by policy-makers to increase
      its acceptability.

PMID- 26310913
TI  - Targeted Assessment for Prevention of Healthcare-Associated Infections: A New
      Prioritization Metric.
AB  - OBJECTIVE: To develop a method for calculating the number of healthcare
      associated infections (HAIs) that must be prevented to reach a HAI reduction goal
      and identifying and prioritizing healthcare facilities where the largest
      reductions can be achieved. SETTING: Acute care hospitals that report HAI data to
      the Centers for Disease Control and Prevention's National Healthcare Safety
      Network. METHODS :The cumulative attributable difference (CAD) is calculated by
      subtracting a numerical prevention target from an observed number of HAIs. The
      prevention target is the product of the predicted number of HAIs and a
      standardized infection ratio goal, which represents a HAI reduction goal. The CAD
      is a numeric value that if positive is the number of infections to prevent to
      reach the HAI reduction goal. We calculated the CAD for catheter-associated
      urinary tract infections for each of the 3,639 hospitals that reported such data
      to National Healthcare Safety Network in 2013 and ranked the hospitals by their
      CAD values in descending order. RESULTS: Of 1,578 hospitals with positive CAD
      values, preventing 10,040 catheter-associated urinary tract infections at 293
      hospitals (19%) with the highest CAD would enable achievement of the national 25%
      catheter-associated urinary tract infection reduction goal. CONCLUSION: The CAD
      is a new metric that facilitates ranking of facilities, and locations within
      facilities, to prioritize HAI prevention efforts where the greatest impact can be
      achieved toward a HAI reduction goal.

PMID- 26310914
TI  - Navigation-specific neural coding in the visual system of Drosophila.
AB  - Drosophila melanogaster are a good system in which to understand the minimal
      requirements for widespread visually guided behaviours such as navigation, due to
      their small brains (adults possess only 100,000 neurons) and the availability of
      neurogenetic techniques which allow the identification of task-specific cell
      types. Recently published data describe the receptive fields for two classes of
      visually responsive neurons (R2 and R3/R4d ring neurons in the central complex)
      that are essential for visual tasks such as orientation memory for salient
      objects and simple pattern discriminations. What is interesting is that these
      cells have very large receptive fields and are very small in number, suggesting
      that each sub-population of cells might be a bottleneck in the processing of
      visual information for a specific behaviour, as each subset of cells effectively
      condenses information from approximately 3000 visual receptors in the eye, to
      fewer than 50 neurons in total. It has recently been shown how R1 ring neurons,
      which receive input from the same areas as the R2 and R3/R4d cells, are necessary
      for place learning in Drosophila. However, how R1 neurons enable place learning
      is unknown. By examining the information provided by different populations of
      hypothetical visual neurons in simulations of experimental arenas, we show that
      neurons with ring neuron-like receptive fields are sufficient for defining a
      location visually. In this way we provide a link between the type of information
      conveyed by ring neurons and the behaviour they support. 

PMID- 26310915
TI  - Dental pain and self-care: a cross-sectional study of people with low socio
      economic status residing in rural India.
AB  - CONTEXT: Self-care is one of the ways in which people without access to
      professional care can actively engage in managing their oral health problems.
      AIM: To find out the prevalence of dental pain and the type of self-care remedies
      utilised for pain relief by people with low socio-economic status residing in
      Kollipara mandal, Guntur district, Andhra Pradesh. SETTINGS AND DESIGN: This was
      a cross-sectional population-based study. METHODS AND MATERIAL: A multistage
      simple random-sampling technique was adopted to obtain an appropriate sample. A
      questionnaire, which consisted of sections on socio-economic and demographic
      variables, dental pain, pain characteristics and self-care remedies utilised to
      combat dental pain, was used to collect data. Statistical analysis used the chi
      square test and descriptive statistics. RESULTS: The survey covered a total
      population of 630 individuals. The mean age of the population was 32.8+/-16.7
      years. Among the total study subjects, 44.1% were male and 55.9% were female. The
      prevalence of dental pain reported during the preceding 6 months was 28.3%.
      Subjects who experienced dental pain reported the home remedies and self-care
      methods that they utilised to get relief from the pain. They more frequently
      reported using over-the-counter medication (49.6%) for pain relief. CONCLUSIONS:
      This study provides an insight into the type and usage of self-care in relief of
      dental pain. Pain sufferers used a variety of self-care methods to deal with
      their problems.

PMID- 26310916
TI  - The Arabidopsis immune regulator SRFR1 dampens defences against herbivory by
      Spodoptera exigua and parasitism by Heterodera schachtii.
AB  - Plants have developed diverse mechanisms to fine tune defence responses to
      different types of enemy. Cross-regulation between signalling pathways may allow
      the prioritization of one response over another. Previously, we identified
      SUPPRESSOR OF rps4-RLD1 (SRFR1) as a negative regulator of ENHANCED DISEASE
      SUSCEPTIBILITY1 (EDS1)-dependent effector-triggered immunity against the
      bacterial pathogen Pseudomonas syringae pv. tomato strain DC3000 expressing
      avrRps4. The use of multiple stresses is a powerful tool to further define gene
      function. Here, we examined whether SRFR1 also impacts resistance to a
      herbivorous insect in leaves and to a cyst nematode in roots. Interestingly,
      srfr1-1 plants showed increased resistance to herbivory by the beet army worm
      Spodoptera exigua and to parasitism by the cyst nematode Heterodera schachtii
      compared with the corresponding wild-type Arabidopsis accession RLD. Using
      quantitative real-time PCR (qRT-PCR) to measure the transcript levels of
      salicylic acid (SA) and jasmonate/ethylene (JA/ET) pathway genes, we found that
      enhanced resistance of srfr1-1 plants to S. exigua correlated with specific
      upregulation of the MYC2 branch of the JA pathway concurrent with suppression of
      the SA pathway. In contrast, the greater susceptibility of RLD was accompanied by
      simultaneously increased transcript levels of SA, JA and JA/ET signalling pathway
      genes. Surprisingly, mutation of either SRFR1 or EDS1 increased resistance to H.
      schachtii, indicating that the concurrent presence of both wild-type genes
      promotes susceptibility. This finding suggests a novel form of resistance in
      Arabidopsis to the biotrophic pathogen H. schachtii or a root-specific regulation
      of the SA pathway by EDS1, and places SRFR1 at an intersection between multiple
      defence pathways. 

PMID- 26310917
TI  - N-Substitution dependent stereoselectivity switch in palladium catalyzed
      hydroalkynylation of ynamides: a regio and stereoselective synthesis of
      ynenamides.
AB  - A highly general palladium catalysed regioselective hydroalkynylation of ynamides
      for versatile enamide building blocks with an alkyne tether is achieved with an N
      substitution dependent stereoselectivity switch under very mild reaction
      conditions. 

PMID- 26310918
TI  - Chemical Disruption of Wnt-dependent Cell Fate Decision-making Mechanisms in
      Cancer and Regenerative Medicine.
AB  - Cell-to-cell signaling molecules such as the Wnt proteins that directly influence
      the expression of cell-type specific transcriptional programs are essential for
      tissue generation in metazoans. The mechanisms supporting cellular responses to
      these molecules represent potential points of intervention for directing cell
      fate outcomes in therapeutic contexts. Small molecules that modulate Wnt-mediated
      cellular responses have proven to be powerful probes for Wnt protein function in
      diverse biological settings including cancer, development, and regeneration.
      Whereas efforts to develop these chemicals as therapeutic agents have dominated
      conversation, the unprecedented modes-of-action associated with these molecules
      and their implications for drug development deserve greater examination. In this
      review, we will discuss how medicinal chemistry efforts focused on first in class
      small molecules targeting two Wnt pathway components--the polytopic Porcupine
      (Porcn) acyltransferase and the cytoplasmic Tankyrase (Tnks) poly-ADP-ribosylases
      -have contributed to our understanding of the druggable genome and expanded the
      armamentarium of chemicals that can be used to influence cell fate decision
      making.

PMID- 26310920
TI  - Potential Relevance of Melatonin Against Some Infectious Agents: A Review and
      Assessment of Recent Research.
AB  - Melatonin, a tryptophan-derived neurohormone found in animals, plants, and
      microbes, participates in various biological and physiological functions. Among
      other properties, numerous in vitro or in vivo studies have reported its
      therapeutic potential against many parasites, bacteria and viruses. In this
      concern, melatonin was found to be effective against many parasites such as
      Plasmodium, Toxoplasma gondii, and Trypansoma cruzi, via various mechanisms such
      as modulation of calcium level and/or host immune system. Likewise, a recent
      investigation has reported in vitro activity of melatonin against Leishmania
      infantum promastigotes which is the causative agent of fascinating visceral
      Leishmaniasis. This review was initially undertaken to summarize some facts about
      certain physiological and therapeutic effects of melatonin. It also reviews the
      effects and action mechanisms of melatonin in bacterial and viral infection
      besides biology of different parasites which may provide a promising strategy for
      control of many diseases of public health importance. 

PMID- 26310919
TI  - Synthetic Small Molecule Inhibitors of Hh Signaling As Anti-Cancer
      Chemotherapeutics.
AB  - The hedgehog (Hh) pathway is a developmental signaling pathway that is essential
      to the proper embryonic development of many vertebrate systems. Dysregulation of
      Hh signaling has been implicated as a causative factor in the development and
      progression of several forms of human cancer. As such, the development of small
      molecule inhibitors of Hh signaling as potential anti-cancer chemotherapeutics
      has been a major area of research interest in both academics and industry over
      the past ten years. Through these efforts, synthetic small molecules that target
      multiple components of the Hh pathway have been identified and advanced to
      preclinical or clinical development. The goal of this review is to provide an
      update on the current status of several synthetic small molecule Hh pathway
      inhibitors and explore the potential of several recently disclosed inhibitory
      scaffolds. 

PMID- 26310921
TI  - 38(th) EUROPEAN SOCIETY OF NEURORADIOLOGY Diagnostic and Interventional ANNUAL
      MEETING.

PMID- 26310922
TI  - Identification of agents effective against multiple toxins and viruses by host
      oriented cell targeting.
AB  - A longstanding and still-increasing threat to the effective treatment of
      infectious diseases is resistance to antimicrobial countermeasures. Potentially,
      the targeting of host proteins and pathways essential for the detrimental effects
      of pathogens offers an approach that may discover broad-spectrum anti-pathogen
      countermeasures and circumvent the effects of pathogen mutations leading to
      resistance. Here we report implementation of a strategy for discovering broad
      spectrum host-oriented therapies against multiple pathogenic agents by multiplex
      screening of drugs for protection against the detrimental effects of multiple
      pathogens, identification of host cell pathways inhibited by the drug, and
      screening for effects of the agent on other pathogens exploiting the same
      pathway. We show that a clinically used antimalarial drug, Amodiaquine,
      discovered by this strategy, protects host cells against infection by multiple
      toxins and viruses by inhibiting host cathepsin B. Our results reveal the
      practicality of discovering broadly acting anti-pathogen countermeasures that
      target host proteins exploited by pathogens. 

PMID- 26310923
TI  - [Perioperative transesophageal echocardiography in non-cardiac surgery. Update].
AB  - AIM: The aim of this article is to impart knowledge concerning focused
      transesophageal echocardiographic examination (TEE) for non-cardiac surgery which
      is an essential part of perioperative monitoring. It allows a rapid
      echocardiographic examination without interference with the surgical field or
      under limited transthoracic examination conditions. New recommendations for a
      comprehensive perioperative TEE examination with expanded standard views and the
      recently published consensus statement for a shortened baseline examination were
      crucial for this study. MATERIAL AND METHODS: The background is the peer-reviewed
      literature from PubMed. RESULTS: Apart from cardiac surgery TEE has two main
      applications: firstly, the evaluation of patients developing acute life
      threatening hemodynamic instability in the operating room, in the emergency room
      or in the intensive care unit (ICU). Secondly, TEE is used as planned
      intraoperative monitoring when severe hemodynamic, pulmonary or neurological
      complications are expected because of the type of surgery or due to the
      cardiopulmonary medical history of the patient. In 2013 a total of 11 relevant
      standard views were defined for the basic perioperative TEE examination in non
      cardiac surgery. These 11 views should be performed for each patient. Appropriate
      extension to a comprehensive examination may be necessary if complex pathology is
      obvious. DISCUSSION: Even in non-cardiac surgery TEE is an important tool
      allowing clarification of a life-threatening perioperative hemodynamic
      instability within a few minutes. Furthermore, the hemodynamic management of high
      risk patients can be facilitated. Appropriate qualification and continuous
      training are necessary in order to assure the competence of the examiner.

PMID- 26310924
TI  - Measurement of specific IgE antibodies to Ses i 1 improves the diagnosis of
      sesame allergy.
AB  - BACKGROUND: The number of reported cases of allergic reactions to sesame seeds
      (Sesamum indicum) has increased significantly. The specific IgE tests and skin
      prick tests presently available for diagnosis of sesame allergy are all based on
      crude sesame extract and are limited by their low clinical specificity. Thus,
      oral food challenge (OFC) is still the gold standard in the diagnosis. OBJECTIVE:
      The aim was to identify the allergen components useful to diagnose sesame
      allergic children with the goal to reduce the number of OFCs needed. METHODS:
      Ninety-two sesame-sensitized children were consecutively enrolled and diagnosed
      based on OFC or convincing history. Specific IgE to purified native 11S globulin
      (nSes i 11S), 7S globulin (nSes i 7S), 2S albumin (nSes i 2S), and two
      recombinant 2S albumins (rSes i 1 and rSes i 2) was measured by ELISA and/or
      ImmunoCAP (rSes i 1/streptavidin application). RESULTS: Based on area under curve
      (AUC) values from receiver operating characteristic (ROC) analysis, rSes i 1 was
      shown to have the best diagnostic performance of the allergen components in
      ELISA. The experimental rSes i 1 ImmunoCAP test had larger AUC (0.891; 95% CI,
      0.826-0.955) compared to the commercially available sesame ImmunoCAP (0.697; 95%
      CI, 0.589-0.805). The clinical sensitivity and specificity for the rSes i 1
      ImmunoCAP test at optimal cut-off (3.96 kUA /L) were 86.1% and 85.7%,
      respectively. CONCLUSION AND CLINICAL RELEVANCE: Sensitization to Ses i 1 is
      strongly associated with clinical sesame allergy. Measurement of specific IgE to
      rSes i 1 could reduce the numbers of OFCs needed.

PMID- 26310925
TI  - Lamivudine-Induced Skin Rash Remains an Underdiagnosed Entity in HIV: A Case
      Series from a Single Center.
AB  - BACKGROUND: Hypersensitivity reaction to antiretroviral treatment (ART) poses
      potential threats in maintenance of treatment. Lamivudine (3TC), is rare to cause
      rash. We are reporting 23 cases of 3TC-induced rash. METHODS: An observational
      study conducted in the antiretroviral treatment center of a tertiary care
      hospital of North India from Feb 2009-Dec 2013 to record 3TC-induced rash. These
      were then recommended to start ART without 3TC and were followed up at 1-, 2-,
      and at 4-week intervals to monitor the toxicity, if any, with alternate therapy.
      RESULTS: We observed 3TC-induced skin rash in 23 HIV-infected individuals (0.7%),
      out of 3213 HIV-infected individuals initiated on first line ART (zidovudine
      [ZDV]/tenofovir [TDF] + 3TC +nevirapine [NVP]/efavirenz [EFV] during the study
      period of 5 years [Feb 2009-Dec 2013]). The mean age of these 23 individuals was
      37.5 +/- 12.8 (17-60) years. Lamivudine rash was more common in women than men (F
      = 19, M = 4), with an overall mean age of 37.5 +/- 12.8 (17-60) years. It was
      generalized, erythematous, maculopapular eruptions associated with intense
      itching with no associated mucosal involvement. Lamivudine was substituted with
      TDF in 19, didanosine (ddl) in 3 and abacavir (ABC) in 1 individual. Mean
      duration of follow-up is 11.1 +/- 12.8 (3-42) months. CD4 count was repeated at 3
      months and showed significant improvement (P = 0.002). CONCLUSION: Lamivudine
      induced rash was found at a frequency of 0.7%. The correct and early recognition
      that the rash is due to 3TC, would save unnecessary substitution to a different
      class of drugs.

PMID- 26310926
TI  - Methylprednisolone attenuates lipopolysaccharide-induced Fractalkine expression
      in kidney of Lupus-prone MRL/lpr mice through the NF-kappaB pathway.
AB  - BACKGROUND: Fractalkine (FKN) is involved in the occurrence and development of
      human lupus nephritis. It is known to be upregulated by lipopolysaccharide (LPS)
      as a stimulus in vivo. MRL/lpr mice have been used as an in vivo model to study
      lupus nephritis. Methylprednisolone (MP) is used widely in the clinical treatment
      of progressive glomerular diseases such as lupus nephritis. The aim of this study
      is to explore the mechanism of LPS induced FKN expression and to determine
      whether other molecular mechanisms contribute to the signaling pathway of MP
      action in MRL/lpr mice. METHODS: Forty-eight female MRL/lpr mice at 12 weeks of
      age were randomly distributed into six groups. Each group received various
      treatments for 8 weeks by receiving twice weekly intraperitoneal injections of
      (1) MP (MP-treated mice), of (2) SC-514 (SC-514-induced mice), of (3) normal
      saline and a single injection of LPS (LPS-induced mice), of (4) MP and a single
      injection of LPS (LPS + MP mice), of (5) SC-514 and a single injection of LPS
      (LPS + SC mice) and of (6) normal saline (control mice). One-way ANOVA was used
      for data analysis and P value <0.05 was considered statistically significantly.
      RESULTS: The expression of FKN and NF-kappaB p65 mRNA was detected by qPCR. The
      expression of FKN protein and the activation of NF-kappaB p65 were detected by
      immunohistochemistry and western blots respectively. The expression of FKN in the
      kidney of LPS induced mice was significantly increased and this was mediated by
      increased expression of NF-kappaB p65 and an increase in NF-kappaB phospho-p65.
      MP reduced proteinuria and ameliorated the renal damage in MRL/lpr mice. MP as
      well as the NF-kappaB inhibitor, SC-514, inhibited the LPS-induced increase of
      expression of FKN and the activation of NF-kappaB. CONCLUSIONS: The results
      indicate that MP attenuates LPS-induced FKN expression in kidney of MRL/lpr mice
      through the NF-kappaB pathway.

PMID- 26310927
TI  - Automated analysis of color tissue Doppler velocity recordings of the fetal
      myocardium using a new algorithm.
AB  - BACKGROUND: Tissue Doppler imaging (TDI) can be used to assess fetal cardiac
      function and it has been shown to detect changes associated with hypoxia in
      animal models. However, the analysis is cumbersome and time consuming. The main
      objective of this study was to evaluate the feasibility of a new algorithm
      developed for the automated analysis of color TDI velocity recordings of the
      fetal myocardium. Furthermore, we wanted to assess the effect of different sizes
      of region of interests (ROI) on the measurement of cardiac cycle time intervals
      and myocardial velocities at different gestations. METHODS: This study included
      analysis of 261 TDI velocity traces obtained from 17 fetal echocardiographic
      examinations performed longitudinally on five pregnant women. Cine-loops of fetal
      cardiac four chamber view were recorded with color overlay in TDI mode and stored
      for off-line analysis. ROIs of different sizes were placed at the level of the
      atrioventricular plane in the septum and in the right and left ventricular walls
      of the fetal heart. An automated algorithm was then used for the analysis of
      velocity traces. RESULTS: Out of the total 261 velocity traces, it was possible
      to analyze 203 (78 %) traces with the automated algorithm. It was possible to
      analyze 93 % (81/87) of traces recorded from the right ventricular wall, 82 %
      (71/87) from the left ventricular wall and 59 % (51/87) from the septum. There
      was a trend towards decreasing myocardial velocities with increasing ROI length.
      However, the cardiac cycle time intervals were similar irrespective of which ROI
      size was used. CONCLUSIONS: An automated analysis of color TDI fetal myocardial
      velocity traces seems feasible, especially for measuring cardiac cycle time
      intervals, and has the potential for clinical application.

PMID- 26310928
TI  - Carbohydrate antigen 19-9 is a useful prognostic marker in esophagogastric
      junction adenocarcinoma.
AB  - The incidence rate of esophagogastric junction (EGJ) adenocarcinoma has been
      rapidly increasing worldwide. Carcinoembryonic antigen (CEA) and carbohydrate
      antigen 19-9 (CA19-9) are major serum tumor markers in gastrointestinal cancers.
      However, the role of these markers in EGJ adenocarcinoma has not been thoroughly
      investigated. A total of 211 patients with EGJ adenocarcinoma who underwent
      surgery or endoscopic submucosal dissection at two academic institutions,
      Kumamoto University Hospital or Kyushu University Hospital between January 1996
      and March 2014, were eligible for this study. Serum CEA and CA19-9 were examined
      within 1 month before resection. The cut-off values for CEA and CA19-9 were set
      at 5.0 ng/mL and 37 U/mL, respectively. The clinicopathological features and
      prognostic roles of the markers were examined using univariate and multivariate
      analyses. The positive ratios for preoperative CEA (>5.0 ng/mL) and CA19-9 (>37
      U/mL) were 20.3% and 12.9%, respectively. The positive ratio of CEA and CA19-9
      was significantly higher in patients with tumors invading muscular or deeper
      layers (P = 0.002 and <0.001, respectively). Cox proportional hazards model
      revealed that CA19-9 positivity, but not CEA positivity, was an independent
      prognostic factor in patients with EGJ adenocarcinoma for cancer-specific
      survival (multivariate hazard ratio [HR] = 3.89, 95% confidence interval [CI]
      1.41-10.33; P = 0.010) and overall survival (multivariate HR = 2.43, 95% CI 1.03
      5.35; P = 0.043). Preoperative serum CA19-9 is a useful prognostic marker in
      patients with EGJ adenocarcinoma.

PMID- 26310929
TI  - Surface Plasmon Enhanced Sensitive Detection for Possible Signature of Majorana
      Fermions via a Hybrid Semiconductor Quantum Dot-Metal Nanoparticle System.
AB  - In the present work, we theoretically propose an optical scheme to detect the
      possible signature of Majorana fermions via the optical pump-probe spectroscopy,
      which is very different from the current tunneling measurement based on
      electrical methods. The scheme consists of a metal nanoparticle and a
      semiconductor quantum dot coupled to a hybrid semiconductor/superconductor
      heterostructures. The results show that the probe absorption spectrum of the
      quantum dot presents a distinct splitting due to the existence of Majorana
      fermions. Owing to surface plasmon enhanced effect, this splitting will be more
      obvious, which makes Majorana fermions more easy to be detectable. The technique
      proposed here open the door for new applications ranging from robust manipulation
      of Majorana fermions to quantum information processing based on Majorana
      fermions. 

PMID- 26310930
TI  - The disruption of mitochondrial axonal transport is an early event in
      neuroinflammation.
AB  - BACKGROUND: In brain inflammatory diseases, axonal damage is one of the most
      critical steps in the cascade that leads to permanent disability. Thus,
      identifying the initial events triggered by inflammation or oxidative stress that
      provoke axonal damage is critical for the development of neuroprotective
      therapies. Energy depletion due to mitochondrial dysfunction has been postulated
      as an important step in the damage of axons. This prompted us to study the
      effects of acute inflammation and oxidative stress on the morphology, transport,
      and function of mitochondria in axons. METHODS: Mouse cerebellar slice cultures
      were challenged with either lipopolysaccharide (LPS) or hydrogen peroxide (H2O2)
      ex vivo for 24 h. Axonal mitochondrial morphology was evaluated by transmission
      electron microscopy (TEM) and mitochondrial transportation by time-lapse imaging.
      In addition, mitochondrial function in the cerebellar slice cultures was analyzed
      through high-resolution respirometry assays and quantification of adenosine
      triphosphate (ATP) production. RESULTS: Both conditions promoted an increase in
      the size and complexity of axonal mitochondria evident in electron microscopy
      images, suggesting a compensatory response. Such compensation was reflected at
      the tissue level as increased respiratory activity of complexes I and IV and as a
      transient increase in ATP production in response to acute inflammation. Notably,
      time-lapse microscopy indicated that mitochondrial transport (mean velocity) was
      severely impaired in axons, increasing the proportion of stationary mitochondria
      in axons after LPS challenge. Indeed, the two challenges used produced different
      effects: inflammation mostly reducing retrograde transport and oxidative stress
      slightly enhancing retrograde transportation. CONCLUSIONS: Neuroinflammation
      acutely impairs axonal mitochondrial transportation, which would promote an
      inappropriate delivery of energy throughout axons and, by this way, contribute to
      axonal damage. Thus, preserving axonal mitochondrial transport might represent a
      promising avenue to exploit as a therapeutic target for neuroprotection in brain
      inflammatory diseases like multiple sclerosis.

PMID- 26310931
TI  - Intraoperative localization of the marginal mandibular nerve: a landmark study.
AB  - BACKGROUND: Identification and preservation of the marginal mandibular nerve
      (MMN) remains an important step in otolaryngology procedures. Current
      publications place the MMN at least 1 cm below the mandible. This study will
      evaluate the accuracy of the method of determining the surgical location of this
      branch of the facial nerve in vivo. METHODS: MMN were examined in 52 consecutive
      otolaryngology patients. Using a validated landmarking scheme, distances were
      measured from the inferior edge of the mandible and the lowest point of the
      nerve. A comparison of 33 nerves pairs was undertaken. Effect of patient's age
      was analysed. RESULTS: Eighty five nerves were landmarked. The mean position of
      the nerve was 0.2-3.4 mm higher than the margin of the mandible. There were no
      significant difference in position with respect to age and left versus right
      comparisons. CONCLUSION: The marginal mandibular nerve (MMN) is significantly
      higher than previously published. The location of the nerve on the right does not
      correlate with the left. Location of the nerve does not correlate with patient's
      age.

PMID- 26310932
TI  - Retinoid X receptor alpha enhances human cholangiocarcinoma growth through
      simultaneous activation of Wnt/beta-catenin and nuclear factor-kappaB pathways.
AB  - Retinoid X receptor alpha (RXRalpha) plays important roles in the malignancy of
      several cancers such as human prostate tumor, breast cancer, and thyroid tumor.
      However, its exact functions and molecular mechanisms in cholangiocarcinoma
      (CCA), a chemoresistant carcinoma with poor prognosis, remain unclear. In this
      study we found that RXRalpha was frequently overexpressed in human CCA tissues
      and CCA cell lines. Downregulation of RXRalpha led to decreased expression of
      mitosis-promoting factors including cyclin D1and cyclin E, and the proliferating
      cell nuclear antigen, as well as increased expression of cell cycle inhibitor
      p21, resulting in inhibition of CCA cell proliferation. Furthermore, RXRalpha
      knockdown attenuated the expression of cyclin D1 through suppression of Wnt/beta
      catenin signaling. Retinoid X receptor alpha upregulated proliferating cell
      nuclear antigen expression through nuclear factor-kappaB (NF-kappaB) pathways,
      paralleled with downregulation of p21. Thus, the Wnt/beta-catenin and NF-kappaB
      pathways account for the inhibition of CCA cell growth induced by RXRalpha
      downregulation. Retinoid X receptor alpha plays an important role in
      proliferation of CCA through simultaneous activation of Wnt/beta-catenin and NF
      kappaB pathways, indicating that RXRalpha might serve as a potential molecular
      target for CCA treatment. 

PMID- 26310933
TI  - Easy parallel screening of reagent stability, quality control, and metrology in
      solid phase peptide synthesis (SPPS) and peptide couplings for microarrays.
AB  - Evaluating the stability of coupling reagents, quality control (QC), and surface
      functionalization metrology are all critical to the production of high quality
      peptide microarrays. We describe a broadly applicable screening technique for
      evaluating the fidelity of solid phase peptide synthesis (SPPS), the stability of
      activation/coupling reagents, and a microarray surface metrology tool. This
      technique was used to assess the stability of the activation reagent 1-{[1-(Cyano
      2-ethoxy-2-oxo-ethylidenaminooxy)dimethylamino
      morpholinomethylene]}methaneaminiumHexafluorophosphate (COMU) (Sigma-Aldrich, St.
      Louis, MO, USA) by SPPS of Leu-Enkephalin (YGGFL) or the coupling of commercially
      synthesized YGGFL peptides to (3-aminopropyl)triethyoxysilane-modified glass
      surfaces. Coupling efficiency was quantitated by fluorescence signaling based on
      immunoreactivity of the YGGFL motif. It was concluded that COMU solutions should
      be prepared fresh and used within 5 h when stored at ~23  degrees C and not
      beyond 24 h if stored refrigerated, both in closed containers. Caveats to gauging
      COMU stability by absorption spectroscopy are discussed. Commercial YGGFL
      peptides needed independent QC, due to immunoreactivity variations for the same
      sequence synthesized by different vendors. This technique is useful in evaluating
      the stability of other activation/coupling reagents besides COMU and as a
      metrology tool for SPPS and peptide microarrays.

PMID- 26310934
TI  - The reading room: Exploring the use of literature as a strategy for integrating
      threshold concepts into nursing curricula.
AB  - In addition to acquiring a solid foundation of clinical knowledge and skills,
      nursing students making the transition from lay person to health professional
      must adopt new conceptual understandings and values, while at the same time
      reflecting on and relinquishing ill-fitting attitudes and biases. This paper
      presents creative teaching ideas that utilise published narratives and explores
      the place of these narratives in teaching threshold concepts to nursing students.
      Appreciating nuance, symbolism and deeper layers of meaning in a well-drawn story
      can promote emotional engagement and cause learners to care deeply about an
      issue. Moreover, aesthetic learning, through the use of novels, memoirs and
      picture books, invites learners to enter into imagined worlds and can stimulate
      creative and critical thinking. This approach can also be a vehicle for
      transformative learning and for enhancing students' understanding and
      internalisation of threshold concepts that are integral to nursing. Guided
      engagement with the story by an effective educator can help learners to examine
      taken-for-granted assumptions, differentiate personal from professional values,
      remember the link between the story and the threshold concept and re-examine
      their own perspectives; this can result in transformative learning. In this
      paper, we show how threshold concepts can be introduced and discussed with
      nursing students via guided engagement with specific literature, so as to prompt
      meaningful internalised learning. 

PMID- 26310935
TI  - CHA2 DS2 VASc Score as a Predictor of Cardiovascular Events in Ambulatory
      Patients without Atrial Fibrillation.
AB  - BACKGROUND: New evidence suggests that the CHA(2)DS(2)VASc (congestive heart
      failure, hypertension [HTN], age, diabetes, stroke, vascular disease, and female
      gender) score may be a reliable tool to predict the risk of thromboembolic events
      in patients without documented atrial fibrillation (AF). METHODS: We performed a
      prospective cohort study of outpatients without AF or flutter, who were not using
      oral anticoagulation. Clinical characteristics were assessed and patients were
      stratified according to the CHA(2)DS(2)VASc score. We evaluated the incidence of
      major adverse cardiac outcomes and its relation to the CHA(2)DS(2)VASc score
      during the follow-up. RESULTS: Four hundred sixty-eight patients without AF were
      enrolled with a mean follow-up of 12 +/- 6 months. Age was 64.9 +/- 11.3 years.
      The prevalence of HTN was 88.4%, diabetes 37.6%, heart failure 26.3%, and
      vascular disease 61.7%. Overall, CHA(2)DS(2)VASc score was 3.4 +/- 1.4. There
      were 15 major adverse cardiac outcomes during 12.2 months of follow-up (overall
      incidence of 3.2 per 100 person-years). We found significant differences in
      relation to gender, age, previous stroke, and follow-up length in patients with
      and without adverse outcomes. The CHA(2)DS(2)VASc score was higher in those with
      adverse outcomes (4.2 +/- 1.7 vs 3.4 +/- 1.4; P = 0.035). Patients with a
      CHA(2)DS(2)VASc >=6 had a relative risk for adverse outcomes of 4.2 (95%
      confidence interval: 1.27-13.90). CONCLUSIONS: In our population, CHA(2)DS(2)VASc
      score predicts major adverse cardiac outcomes, including stroke and death, in a
      cohort of patients without AF.

PMID- 26310936
TI  - Effect of an acute increase in central blood volume on cerebral hemodynamics.
AB  - Systemic blood distribution is an important factor involved in regulating
      cerebral blood flow (CBF). However, the effect of an acute change in central
      blood volume (CBV) on CBF regulation remains unclear. To address our question, we
      sought to examine the CBF and systemic hemodynamic responses to microgravity
      during parabolic flight. Twelve healthy subjects were seated upright and exposed
      to microgravity during parabolic flight. During the brief periods of
      microgravity, mean arterial pressure was decreased (-26 +/- 1%, P < 0.001),
      despite an increase in cardiac output (+21 +/- 6%, P < 0.001). During
      microgravity, central arterial pulse pressure and estimated carotid sinus
      pressure increased rapidly. In addition, this increase in central arterial pulse
      pressure was associated with an arterial baroreflex-mediated decrease in heart
      rate (r = -0.888, P < 0.0001) and an increase in total vascular conductance (r =
      0.711, P < 0.001). The middle cerebral artery mean blood velocity (MCA Vmean)
      remained unchanged throughout parabolic flight (P = 0.30). During microgravity
      the contribution of cardiac output to MCA Vmean was gradually reduced (P < 0.05),
      and its contribution was negatively correlated with an increase in total vascular
      conductance (r = -0.683, P < 0.0001). These findings suggest that the acute
      loading of the arterial and cardiopulmonary baroreceptors by increases in CBV
      during microgravity results in acute and marked systemic vasodilation.
      Furthermore, we conclude that this marked systemic vasodilation decreases the
      contribution of cardiac output to CBF. These findings suggest that the arterial
      and cardiopulmonary baroreflex-mediated peripheral vasodilation along with
      dynamic cerebral autoregulation counteracts a cerebral overperfusion, which
      otherwise would occur during acute increases in CBV. 

PMID- 26310937
TI  - Influence of acute and chronic streptozotocin-induced diabetes on the rat tendon
      extracellular matrix and mechanical properties.
AB  - Diabetes is a major risk factor for tendinopathy, and tendon abnormalities are
      common in diabetic patients. The purpose of the present study was to evaluate the
      effect of streptozotocin (60 mg/kg)-induced diabetes and insulin therapy on
      tendon mechanical and cellular properties. Sprague-Dawley rats (n = 40) were
      divided into the following four groups: nondiabetic (control), 1 wk of diabetes
      (acute), 10 wk of diabetes (chronic), and 10 wk of diabetes with insulin
      treatment (insulin). After 10 wk, Achilles tendon and tail fascicle mechanical
      properties were similar between groups (P > 0.05). Cell density in the Achilles
      tendon was greater in the chronic group compared with the control and acute
      groups (control group: 7.8 +/- 0.5 cells/100 MUm(2), acute group: 8.3 +/- 0.4
      cells/100 MUm(2), chronic group: 10.9 +/- 0.9 cells/100 MUm(2), and insulin
      group: 9.2 +/- 0.8 cells/100 MUm(2), P < 0.05). The density of proliferating
      cells in the Achilles tendon was greater in the chronic group compared with all
      other groups (control group: 0.025 +/- 0.009 cells/100 MUm(2), acute group: 0.019
      +/- 0.005 cells/100 MUm(2), chronic group: 0.067 +/- 0.015, and insulin group:
      0.004 +/- 0.004 cells/100 MUm(2), P < 0.05). Patellar tendon collagen content was
      ~32% greater in the chronic and acute groups compared with the control or insulin
      groups (control group: 681 +/- 63 MUg collagen/mg dry wt, acute group: 938 +/- 21
      MUg collagen/mg dry wt, chronic: 951 +/- 52 MUg collagen/mg dry wt, and insulin
      group: 596 +/- 84 MUg collagen/mg dry wt, P < 0.05). In contrast, patellar tendon
      hydroxylysyl pyridinoline cross linking and collagen fibril organization were
      unchanged by diabetes or insulin (P > 0.05). Our findings suggest that 10 wk of
      streptozotocin-induced diabetes does not alter rat tendon mechanical properties
      even with an increase in collagen content. Future studies could attempt to
      further address the mechanisms contributing to the increase in tendon problems
      noted in diabetic patients, especially since our data suggest that hyperglycemia
      per se does not alter tendon mechanical properties. 

PMID- 26310938
TI  - Role played by NaV 1.7 channels on thin-fiber muscle afferents in transmitting
      the exercise pressor reflex.
AB  - Voltage-gated sodium channels (NaV) 1.7 are highly expressed on the axons of
      somatic afferent neurons and are thought to play an important role in the
      signaling of inflammatory pain. NaV 1.7 channels are classified as tetrodotoxin
      (TTX)-sensitive, meaning that they are blocked by TTX concentrations of less than
      300 nM. These findings prompted us to determine in decerebrated, unanesthetized
      rats, the role played by NaV 1.7 channels in the transmission of muscle afferent
      input evoking the exercise pressor reflex. We first showed that the exercise
      pressor reflex, which was evoked by static contraction of the triceps surae
      muscles, was reversibly attenuated by application of 50 nM TTX, but not 5 nM TTX,
      to the L4-L5 dorsal roots (control: 21 +/- 1 mmHg, TTX: 8 +/- 2 mmHg, recovery:
      21 +/- 3 mmHg; n = 6; P < 0.01). We next found that the peak pressor responses to
      contraction were significantly attenuated by dorsal root application of 100 nM
      Ssm6a, a compound that is a selective NaV 1.7 channel inhibitor. Removal of Ssm6a
      restored the reflex to its control level (control: 19 +/- 3 mmHg, Ssm6a: 10 +/- 1
      mmHg, recovery: 19 +/- 4 mmHg; n = 6; P < 0.05). Compound action potentials
      recorded from the L4 and L5 dorsal roots and evoked by single-pulse stimulation
      of the sciatic nerve showed that both TTX and Ssm6a attenuated input from group
      III, as well as group IV afferents. We conclude that NaV 1.7 channels play a role
      in the thin-fiber muscle afferent pathway evoking the exercise pressor reflex. 

PMID- 26310939
TI  - Principles of the prolactin/vasoinhibin axis.
AB  - The hormonal family of vasoinhibins, which derive from the anterior pituitary
      hormone prolactin, are known for their inhibiting effects on blood vessel growth,
      vasopermeability, and vasodilation. As pleiotropic hormones, vasoinhibins act in
      multiple target organs and tissues. The generation, secretion, and regulation of
      vasoinhibins are embedded into the organizational principle of an axis, which
      integrates the hypothalamus, the pituitary, and the target tissue
      microenvironment. This axis is designated as the prolactin/vasoinhibin axis.
      Disturbances of the prolactin/vasoinhibin axis are associated with the
      pathogenesis of retinal and cardiac diseases and with diseases occurring during
      pregnancy. New phylogenetical, physiological, and clinical implications are
      discussed. 

PMID- 26310941
TI  - Effect of health Baduanjin Qigong for mild to moderate Parkinson's disease.
AB  - AIM: The present study investigated the effectiveness of Baduanjin Qigong on
      symptoms related to gait, functional mobility and sleep in Parkinson disease (PD)
      patients. METHODS: A total of 100 patients (age 67.53 +/- 8.56 years, range 55-80
      years) with mild to moderate PD were randomly assigned to two groups.
      Participants in the Baduanjin Qigong group (BQG) received a Baduanjin Qigong
      program, consisting of four 45-min sessions each week and daily walking 30 min
      for 6 months. Participants in the control group were carried out daily walking
      for 30 min. Pre- and post-intervention testing was carried out to assess sleep
      quality, fatigue, functional mobility and gait performance in these participants.
      RESULTS: After the 6-month Baduanjin Qigong intervention, the BQG showed sleep
      quality improvements in the Unified Parkinson's Disease Rating Scale score (P =
      0.049), Parkinson's Disease Sleep Scale-2 (PDSS-2) total score (P = 0.039), Motor
      Symptoms at Night (PDSS-2) score (P = 0.039), PD Symptoms at Night (PDSS-2) score
      (P = 0.029), Disturbed Sleep (PDSS-2) score (P = 0.037). The BQG showing
      functional mobility capacity greater improvements in the Berg Balance Scale (P =
      0.041) and 6-minute walk test (P = 0.042), and greater decrease in the Timed Up &
      Go (s; P = 0.046). The BQG showing gait function increased in the gait speed
      (m/s; P = 0.011). However, this was not the case for the control group, which
      remained at the same level as pretest performance. CONCLUSIONS: BQG improved the
      gait performance, functional mobility and sleep quality in older adults with PD
      at the 6-month follow up. It is as an alternative home exercise program for older
      adults in rehabilitation for PD. Geriatr Gerontol Int 2016; 16: 911-919.

PMID- 26310940
TI  - Blockade of CD40 ligand for intercellular communication reduces hypertension,
      placental oxidative stress, and AT1-AA in response to adoptive transfer of CD4+ T
      lymphocytes from RUPP rats.
AB  - Preeclampsia (PE) is associated with altered immune activation during pregnancy.
      We have previously shown that adoptive transfer of CD4(+) T cells from the
      reduced uterine perfusion pressure (RUPP) rat model of PE increases blood
      pressure, oxidative stress (ROS), and inflammation in normal pregnant recipient
      rats. The objective of this study was to determine if blockade of communication
      via the CD40-CD40 ligand (CD40L) interaction between placental ischemia-induced
      CD4(+) T cells with endogenous normal pregnant (NP) cells would improve
      pathophysiology that was previously observed in NP recipient rats of RUPP CD4(+)
      T cells. Splenic CD4(+) T lymphocytes were magnetically separated, incubated with
      2.5 MUg/ml anti-CD40 ligand (alphaCD40L) overnight, and transferred into NP rats
      on day 12 of gestation (NP+RUPP CD4(+) T+anti-CD40L). On day 19 of gestation,
      blood pressure (MAP), blood, and tissues were collected. MAP was 99 +/- 2 in NP
      (n = 13), 116 +/- 4 in NP+RUPP CD4(+) T cells (n = 7; P < 0.01); MAP only
      increased to 104 +/- 2 in NP+RUPP CD4(+) T cells+CD40L (n = 24) (P < 0.05 vs.
      NP+RUPP CD4(+) T cells). Mechanisms of hypertension in response to RUPP CD4(+) T
      cells include endothelin-1 (ET-1), ROS, and angiotensin II type I receptor (AT1
      AA) were analyzed. Inhibition of CD40L binding reduced placental ET-1 to 2.3-fold
      above NP rats and normalized placental ROS from 318.6 +/- 89 in NP+RUPP CD4(+) T
      cells (P < 0.05) to 118.7 +/- 24 in NP+RUPP CD4(+) T+anti-CD40L (P < 0.05). AT1
      AA was also normalized with inhibition of CD40L. These data suggest that
      placental ischemia-induced T-cell communication via the CD40L is one important
      mechanism leading to much of the pathophysiology of PE. 

PMID- 26310942
TI  - Pinellia ternata lectin exerts a pro-inflammatory effect on macrophages by
      inducing the release of pro-inflammatory cytokines, the activation of the nuclear
      factor-kappaB signaling pathway and the overproduction of reactive oxygen
      species.
AB  - Pinellia ternata (PT) is a widely used traditional Chinese medicine. The raw
      material has a throat-irritating toxicity that is associated with the PT lectin
      (PTL). PTL is a monocot lectin isolated from the tubers of PT, which exhibits
      mouse peritoneal acute inflammatory effects in vivo. The present study aimed to
      investigate the pro-inflammatory effect of PTL on macrophages. PTL (50 ug/ml)
      stimulated macrophages enhanced the chemotactic activity of neutrophils. PTL (50,
      100, 200 and 400 ug/ml) significantly elevated the production of cytokines [tumor
      necrosis factor-alpha (TNF-alpha) , interleukin (IL)-1beta and IL-6]. PTL (25, 50
      and 100 ug/ml) induced intracellular reactive oxygen species (ROS)
      overproduction. PTL also caused transfer of p65 from the macrophage cytoplasm to
      the nucleus and activated the nuclear factor-kappaB (NF-kappaB) signaling
      pathway. Scanning electron microscope images revealed severe cell swelling and
      membrane integrity defection of macrophages following PTL (100 ug/ml)
      stimulation, which was also associated with inflammation. PTL had pro
      inflammatory activity, involving induced neutrophil migration, cytokine release,
      ROS overproduction and the activation of the NF-kappaB signaling pathway, which
      was associated with the activation of macrophages. 

PMID- 26310943
TI  - Treatment outcomes and their determinants in HIV patients on Anti-retroviral
      Treatment Program in selected health facilities of Kembata and Hadiya zones,
      Southern Nations, Nationalities and Peoples Region, Ethiopia.
AB  - BACKGROUND: Ethiopia has been providing free Antiretroviral Treatment (ART) since
      2005 for HIV/AIDS patients. ART improves survival time and quality of life of HIV
      patients but ART treatment outcomes might be affected by several factors.
      However, factors affecting treatment outcomes are poorly understood in Ethiopia.
      Hence, this study assesses treatment outcomes and its determinants for HIV
      patients on ART in selected health facilities of Kembata and Hadiya zones.
      METHODS: A retrospective cohort study was conducted on 730 adult HIV/AIDS
      patients who enrolled antiretroviral therapy from 2007 to 2011 in four selected
      health facilities of Kembata and Hadiya zones of Southern Ethiopia. Study
      subjects were sampled from the health facilities based on population proportion
      to size. Data was abstracted using data extraction format from medical records.
      Kaplan-Meier survival function was used to estimate survival probability. Cox
      proportional hazards regression model was used to identify factors associated
      with time to death. RESULT: Median age of patients was 32.4 years with Inter
      Quartile Range (IQR) [15, 65]. The female to male ratio of the study
      participants' was 1.4:1. Median CD4 count significantly increased during the last
      four consecutive years of follow up. A total of 92 (12.6%) patients died,
      106(14.5%) were lost to follow-up, and 109(15%) were transferred out. Sixty three
      (68%) deaths occurred in the first 6 months of treatment. The median survival
      time was 25 months with IQR [9, 43]. After adjustment for confounders, WHO
      clinical stage IV [HR 2.42; 95% CI, 1.19, 5.86], baseline CD4 lymphocyte counts
      of 201 cell/mm(3) and 350 cell/mm(3) [HR 0.20; 95 % CI; 0.09-0.43], poor regimen
      adherence [HR 2.70 95% CI: 1.4096, 5.20], baseline hemoglobin level of 10 gm/dl
      and above [HR 0.23; 95% CI: 0.14, 0.37] and baseline functional status of
      bedridden [HR 3.40; 95% CI: 1.61, 7.21] were associated with five year survival
      of HIV patients on ART. CONCLUSION: All people living with HIV/AIDS should
      initiate ART as early as possible. Initiation of ART at the early stages of the
      disease, before deterioration of the functional status of the patients and before
      the reduction of CD4 counts and hemoglobin levels with an intensified health
      education on adherence to ART regimen is recommended.

PMID- 26310944
TI  - Improvement in Hemodynamics After Methylene Blue Administration in Drug-Induced
      Vasodilatory Shock: A Case Report.
AB  - INTRODUCTION: The purpose of this study is to describe a case where methylene
      blue improved hemodynamics in a poisoned patient. CASE REPORT: This is a single
      case report where a poisoned patient developed vasodilatory shock following
      ingestion of atenolol, amlodipine, and valsartan. Shock persisted after multiple
      therapies including vasopressors, high-dose insulin, hemodialysis, and 20%
      intravenous fat emulsion. Methylene blue (2 mg/kg IV over 30 min) was
      administered in the ICU with temporal improvement as measured by pulmonary artery
      catheter hemodynamic data pre- and post-methylene blue administration. Within 1 h
      of methylene blue administration, systemic vascular resistance improved (240 dyn
      s/cm5 increased to 1204 dyn s/cm5), and vasopressor requirements decreased with
      maintenance of mean arterial pressure 60 mmHg. DISCUSSION: Methylene blue may
      improve hemodynamics in drug-induced vasodilatory shock and should be considered
      in critically ill patients poisoned with vasodilatory medications refractory to
      standard therapies.

PMID- 26310945
TI  - Host genetic diversity influences the severity of Pseudomonas aeruginosa
      pneumonia in the Collaborative Cross mice.
AB  - BACKGROUND: Pseudomonas aeruginosa is one of the top three causes of
      opportunistic infections in humans. Patients with a compromised immune system,
      due to immunosuppressive therapies or underlying diseases such as cancer, AIDS or
      the hereditary disease cystic fibrosis, are at risk of developing P. aeruginosa
      infection. However, clinical evidence indicates extremely variable outcomes of P.
      aeruginosa infections in individuals at risk, suggesting that host multi-complex
      genetic traits may influence the severity of this opportunistic infection. Here,
      we have used an innovative experimental model to dissect whether host genetic
      background, such as those found in the outbred population, could influence the
      risk of morbidity and mortality to P. aeruginosa pneumonia. RESULTS: A highly
      genetically-diverse mouse resource population, Collaborative Cross (CC) mice, was
      infected with a clinical strain of P. aeruginosa and subsequently monitored for
      mortality, mean survival time, and morbidity, change in body weight for seven
      days post infection. Disease phenotypes ranged from complete resistance and
      recovery of body weight to lethal disease. Initial variables, including body
      weight, age and gender, have limited influence on P. aeruginosa outcome,
      emphasizing the role of host genetic background in defining the risk of morbidity
      and mortality. When broad-sense heritability of phenotypic traits was evaluated,
      it confirmed the influence of genetic profile rather than environmental factors
      among the CC lines during P. aeruginosa infection. CONCLUSION: This innovative
      model system can potentially reproduce the variables responses of disease
      severity observed in humans during P. aeruginosa pneumonia. Our results
      demonstrated that a widely-marked differential response to P. aeruginosa airway
      infection in term of morbidity and mortality, is mainly affected by host genetic
      factors, as multiple genetic loci or polymorphic variations.

PMID- 26310946
TI  - Corrigendum.

PMID- 26310947
TI  - Twist-drill craniotomy for the treatment of chronic subdural hematomas and the
      use of the pre-coronal suture entry point.

PMID- 26310949
TI  - StratBAM: A Discrete-Event Simulation Model to Support Strategic Hospital Bed
      Capacity Decisions.
AB  - The ability to accurately measure and assess current and potential health care
      system capacities is an issue of local and national significance. Recent joint
      statements by the Institute of Medicine and the Agency for Healthcare Research
      and Quality have emphasized the need to apply industrial and systems engineering
      principles to improving health care quality and patient safety outcomes. To
      address this need, a decision support tool was developed for planning and
      budgeting of current and future bed capacity, and evaluating potential process
      improvement efforts. The Strategic Bed Analysis Model (StratBAM) is a discrete
      event simulation model created after a thorough analysis of patient flow and data
      from Geisinger Health System's (GHS) electronic health records. Key inputs
      include: timing, quantity and category of patient arrivals and discharges; unit
      level length of care; patient paths; and projected patient volume and length of
      stay. Key outputs include: admission wait time by arrival source and receiving
      unit, and occupancy rates. Electronic health records were used to estimate
      parameters for probability distributions and to build empirical distributions for
      unit-level length of care and for patient paths. Validation of the simulation
      model against GHS operational data confirmed its ability to model real-world data
      consistently and accurately. StratBAM was successfully used to evaluate the
      system impact of forecasted patient volumes and length of stay in terms of
      patient wait times, occupancy rates, and cost. The model is generalizable and can
      be appropriately scaled for larger and smaller health care settings. 

PMID- 26310948
TI  - A Soft Computing Approach to Kidney Diseases Evaluation.
AB  - Kidney renal failure means that one's kidney have unexpectedly stopped
      functioning, i.e., once chronic disease is exposed, the presence or degree of
      kidney dysfunction and its progression must be assessed, and the underlying
      syndrome has to be diagnosed. Although the patient's history and physical
      examination may denote good practice, some key information has to be obtained
      from valuation of the glomerular filtration rate, and the analysis of serum
      biomarkers. Indeed, chronic kidney sickness depicts anomalous kidney function
      and/or its makeup, i.e., there is evidence that treatment may avoid or delay its
      progression, either by reducing and prevent the development of some associated
      complications, namely hypertension, obesity, diabetes mellitus, and
      cardiovascular complications. Acute kidney injury appears abruptly, with a rapid
      deterioration of the renal function, but is often reversible if it is recognized
      early and treated promptly. In both situations, i.e., acute kidney injury and
      chronic kidney disease, an early intervention can significantly improve the
      prognosis. The assessment of these pathologies is therefore mandatory, although
      it is hard to do it with traditional methodologies and existing tools for problem
      solving. Hence, in this work, we will focus on the development of a hybrid
      decision support system, in terms of its knowledge representation and reasoning
      procedures based on Logic Programming, that will allow one to consider
      incomplete, unknown, and even contradictory information, complemented with an
      approach to computing centered on Artificial Neural Networks, in order to weigh
      the Degree-of-Confidence that one has on such a happening. The present study
      involved 558 patients with an age average of 51.7 years and the chronic kidney
      disease was observed in 175 cases. The dataset comprise twenty four variables,
      grouped into five main categories. The proposed model showed a good performance
      in the diagnosis of chronic kidney disease, since the sensitivity and the
      specificity exhibited values range between 93.1 and 94.9 and 91.9-94.2 %,
      respectively.

PMID- 26310950
TI  - A Semi-Automatic Coronary Artery Segmentation Framework Using Mechanical
      Simulation.
AB  - CVD (cardiovascular disease) is one of the biggest threats to human beings
      nowadays. An early and quantitative diagnosis of CVD is important in extending
      lifespan and improving people's life quality. Coronary artery stenosis can
      prevent CVD. To diagnose the degree of stenosis, the inner diameter of coronary
      artery needs to be measured. To achieve such measurement, the coronary artery is
      segmented by using a method that is based on morphology and the continuity
      between computed tomography image slices. A centerline extraction method based on
      mechanical simulation is proposed. This centerline extraction method can figure
      out a basic framework of the coronary artery by simulating pixel dots of the
      artery image into mass points. Such mass points have tensile forces, with which
      the outer pixel dots can be drawn to the center. Subsequently, the centerline of
      the coronary artery can be outlined by using the local line-fitting method.
      Finally, the nearest point method is adopted to measure the inner diameter.
      Experimental results showed that the methods proposed in this paper can precisely
      extract the centerline of the coronary artery and can accurately measure its
      inner diameter, thereby providing a basis for quantitative diagnosis of coronary
      artery stenosis. 

PMID- 26310951
TI  - Kinetic modeling of AS(III) and AS(V) adsorption by a novel tetravalent manganese
      feroxyhyte.
AB  - HYPOTHESIS: The purpose of the present work is the development of a kinetic model
      for the adsorption of As(III) and As(V) onto tetravalent manganese feroxyhyte
      (delta-Fe0.75Mn0.25OOH), which have been recently proved to be very efficient
      adsorbent for the particular species. EXPERIMENTS: In this respect equilibrium
      and adsorption kinetic experiments onto this type of adsorbent for As(III) and
      As(V) were performed. Two sizes of adsorbate particles are tested in order to
      acquire better insight to the adsorption process. RESULTS: The adsorption kinetic
      curves cannot be described by the well-known adsorption kinetic models so a
      detailed model that takes into account the structure of the adsorbent particle is
      developed. The model parameters were extracted by the requirement of agreement
      between model and experimental results. The batch model developed here is
      necessary for the development of models for fixed bed adsorption devices in order
      to exploit the commercial prospects of the particular adsorbent. This work
      constitutes the first attempt of kinetic study and adsorption model development
      for the specific very promising adsorbent.

PMID- 26310952
TI  - Photocatalytic oxidation desulfurization of model diesel over
      phthalocyanine/La0.8Ce0.2NiO3.
AB  - A series highly efficient and stable metallophthalocyanine/La0.8Ce0.2NiO3
      (ML/LCNO) photocatalysts were prepared by a facile sol-gel and immersion method.
      The as-prepared samples were characterized by X-ray diffraction (XRD), X-ray
      photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), TEM, N2
      adsorption-desorption, and UV-Vis. The results revealed that LCNO calcined at 700
      degrees C possessed a perovskite structure with porous, and phthalocyanine not
      only adsorbed on the surface but also loaded in the pores of the LCNO oxide. The
      photocatalytic activities of the samples were evaluated by the photocatalytic
      oxidation of dibenzothiophene (DBT) under simulated sunlight irradiation. It was
      found that either macrocyclic structure or center metal of phthalocyanine had
      great influences on the photocatalytic activity of ML/LCNO. The oxidative
      reactivity of the different macrocycles was found in the order of
      MPc/LCNO>MTAP/LCNO>MPTpz/LCNO; which of different center metals was
      CoL/LCNO>FeL/LCNO>MnL/LCNO>NiL/LCNO>CuL/LCNO. The catalysts were reused several
      times with a slight decrease in activity. Furthermore, this kinetics of
      photocatalytic oxidation of DBT indicated that the reaction was a pseudo-first
      order reaction. 

PMID- 26310953
TI  - [Awareness survey of Healthcare Number System pros and cons according to medical
      doctors in Japan].
AB  - OBJECTIVES: After bills to launch the Social Security and Tax Number System were
      enacted in 2013, health and political officials have considered the Healthcare
      Number System (the System). However, little is known about doctors' awareness and
      concerns about the System. This study aimed to measure how many doctors disagree
      with the System, examine the doctors' characteristics, and analyze the benefits
      and harms of the System that they identified. METHODS: A cross-sectional survey
      was conducted of doctors via the Internet. The participants were selected from a
      convenience sample of a panel of doctors based on stratified sampling including
      four groups: working at a hospital and <45 years; working at a hospital and >=45
      years; working at a clinic and <45 years; and working at a clinic and >=45 years.
      The main outcome was how many doctors agreed or disagreed with the System. The
      prevalence was calculated for each group, and their characteristics were examined
      using multivariable logistic regression analysis. The responses to open-ended
      questions concerning the Systems' benefits and harms were analyzed using
      qualitative content analysis. RESULTS: There were 562 respondents (68%). By
      group, 16/143 (11%), 25/138 (18%), 31/132 (23%), and 43/149 (29%) doctors,
      respectively, thought that the System was unnecessary. The variables that
      correlated with the main outcome were age (per 5 years; odds ratio [95%
      confidence interval], 1.14 [1.01-1.29]) and type of medical facility (working at
      a clinic; 1.99 [1.30-3.08]). The doctors identified that unifying information
      could decrease administrative duties, facilitate inter-facility collaboration,
      and prevent inappropriate medical consultations. This could result in decreased
      healthcare costs and personalized healthcare. However, the doctors also
      identified that integrating information and dealing with big data could increase
      information leakage and information management, cause over-monitoring of doctors,
      and enable the inappropriate use of integrated information. This could result in
      deteriorating healthcare. Since some information should not be integrated, the
      System raises ethical considerations about privacy. CONCLUSION: Among the doctors
      surveyed here, 10-30% thought the System was unnecessary. These respondents
      tended to be older and work at a clinic. The System could decrease the cost of
      healthcare and enable personalized healthcare but could also increase information
      leakage and information management, cause over-monitoring of doctors, and enable
      the inappropriate use of integrated information. Prior to System introduction, we
      should facilitate consensus-building about protecting and utilizing personal
      information as well as consider the related ethical issues, and doctors'
      characteristics and concerns.

PMID- 26310954
TI  - [Creating a "Health Promotion Checklist for Residents" Attempt to promote healthy
      activities].
AB  - OBJECTIVE: To create a "Health Promotion Checklist for Residents" to help promote
      healthy habits among local residents. METHODS: First, we investigated items for a
      health promotion checklist in the Health Japan 21 (2(nd) edition) and other
      references. Next, we conducted a questionnaire survey including these checklist
      items in August 2012. The study subjects were randomly selected Hatsukaichi city
      residents aged >=20 years. Anonymous survey forms explaining this study were
      mailed to the investigated subjects and recovered in return envelopes. Data were
      compared by sex and age group. RESULTS: We created a checklist comprising a 23
      item health promotion evaluation index with established scoring. There were 33
      questions regarding health checkups; cancer screenings; dental checkups, blood
      pressure; glycated hemoglobin or blood glucose; dyslipidemia; body mass index;
      number of remaining teeth; breakfast, vegetable, fruit, and salt intake; nutrient
      balance; exercise; smoking; drinking; sleep; stress; and mental state. There were
      also questions on outings, community involvement, activities to improve health,
      and community connections. The questions were classified into six categories:
      health management, physical health, dietary and exercise habits, indulgences,
      mental health, and social activities. Of the 4,002 distributed survey forms,
      1,719 valid responses were returned (recovery rate, 43.0%). The mean score by
      category was 1.69 (N=1,343) for health management, 6.52 (N=1,444) for physical
      health, 12.97 (N=1,511) for dietary and exercise habits, and 2.29 (N=1,518) for
      indulgences, all of which were higher for women, and 5.81 (N=1,469) for mental
      health, which was higher for men. The health management scores were higher among
      subjects in their 40s and 50s. The physical health score increased gradually with
      age from the 70 s and older to the 20 s, whereas the dietary and exercise habits
      increased gradually from the 20 s to the 70 s and older. The 20 s had high scores
      for indulgences, while mental health was low for the 20 s and 30 s and gradually
      increased from the 40 s to the 70 s and older. The social activities score (1.93;
      N=1,539) tended to be higher in the 40 s and older. CONCLUSION: Here we created
      and attempted to validate a checklist that promotes healthy habits nd found that
      subjects were able to use it to examine their living habits.

PMID- 26310955
TI  - [Factors associated with perceived effectiveness of health promotion messages
      among Japanese adults Focus on socioeconomic status].
AB  - OBJECTIVES: Responses and receptiveness to messages advocating health promotion
      are expected to vary according to differences in personal characteristics. To
      increase communication effectiveness, this study examined the differences in
      perceptions of the effectiveness of messages among Japanese adults by
      socioeconomic status and other characteristics. METHODS: A structured
      questionnaire survey was administered to residents aged 30-59 randomly selected
      in two cities (Yamaguchi and Iwakuni) of Yamaguchi prefecture. The questionnaire
      consisted of items on sociodemographic characteristics including sex, age,
      marital status, education, and household income; the perceived effectiveness of
      health messages; and other factors. The subjects were shown different messages on
      several themes (smoking cessation, cancer screening, weight gain) and asked to
      select those that they considered most effective. The associations between
      perception and subjects' sociodemographic characteristics were analyzed. RESULTS:
      A total of 445 subjects responded (response rate, 37.1%). The negative messages
      (health effects of risk behaviors) were generally perceived as the most
      effective. Sex, age, marital status, education, and income were significantly
      associated with the perceived effectiveness of health messages: higher income was
      significantly associated with secondhand smoke in the case of smoking cessation,
      lower income was associated with addiction in the case of drinking restraints,
      lower education and middle income were associated with affection, and lower
      income was associated with own expense in the case of cancer screening.
      CONCLUSION: Despite some differences among the health themes, personal
      characteristics including age, sex, and marital and socioeconomic status were
      associated with the perceived effectiveness of health messages, and our results
      suggest that health communication may be made more effective by consideration of
      the sociodemographic characteristics of target populations and subjects.

PMID- 26310956
TI  - [Characteristics of elderly people registering with emergency contacts systems
      Case study of "elderly monitoring key ring"].
AB  - OBJECTIVES: Here we investigated the characteristics of users of an emergency
      system that tracks elderly people, known as the "elderly monitoring key ring."
      The relevance of a spreading policy or strategy and the user characteristics were
      investigated to develop programs conducted by local governments to manage
      unidentified elderly people with dementia. METHODS: A questionnaire was conducted
      in July 2013 in a district of the Ota Ward in Tokyo. The questionnaire was
      administered to residents >65 years of age (N=7,608), of which 5,166 (67.9%)
      responded. Fully completed responses (N=4,475) were analyzed with binomial
      logistic regression analysis using "monitoring key rings" as the dependent
      variable and simultaneously inputted sex, age, living arrangement, social
      isolation, Instrumental Activities of Daily Living (IADL), and complaints of
      memory loss as independent variables. Interviews were also conducted in August
      2014 of the staff members (N=12) of six community comprehensive support centers
      in the Ota Ward. RESULTS: The logistic regression analysis results indicated that
      women used the monitoring key rings 1.64 times more often than men, late elderly
      used it 4.39 times more often than early elderly, elderly living alone used it
      2.14 times more often than elderly not living alone, non-isolated people used it
      1.36 times more often than isolated people, IADL non-independent people used it
      1.50 times more often than independent people, and people with complaints of
      memory loss used it 1.37 times more often than those without such complaints. On
      the other hand, the results of interviews indicated that elderly people living
      alone, those with worries, and relatively young and healthy elderly people were
      targets. The main targets of community comprehensive support centers were elderly
      individuals living alone and early elderly individuals. The utilization rate of
      elderly people living alone was high; however, that of early elderly people was
      low. They recognized that people registered with the system tended to have high
      anxiety, be relatively young and highly independent, and register after learning
      about the system from their peers or through neighborhood associations.
      CONCLUSION: Individuals who were female, late elderly, elderly living alone, non
      isolated, IADL non-independent, or had complaints of memory loss were most likely
      to be registered with the key ring. The circumstance of registration which
      community comprehensive support centers recognize related to the low utilization
      rate of elderly people who are isolated. In the future, the system should be
      introduced to socially isolated as well as relatively young elderly people.

PMID- 26310957
TI  - The evidence base for transition is bigger than you might think.

PMID- 26310958
TI  - 'It's just a fluid level'.

PMID- 26310959
TI  - Treated Behavioral Symptoms and Mortality in Medicare Beneficiaries in Nursing
      Homes with Alzheimer's Disease and Related Dementias.
AB  - OBJECTIVES: To assess changes in behavioral symptoms associated with Alzheimer's
      disease and related dementias (ADRDs) after antipsychotic (AP) or antidepressant
      (AD) treatment and to estimate the effect of treatment response on mortality
      risk. DESIGN: Retrospective cohort study using 2006-2009 Medicare administrative
      and prescription drug claims data linked to Minimum Data Set 2.0. SETTING: Long
      stay (>=101 days) nursing home residents. PARTICIPANTS: Continuously enrolled fee
      for-service Medicare beneficiaries who had ADRDs, initiated (no use in prior 6
      months) AP (n = 2,035) or AD (n = 1,661) treatment during or after one or more
      behavioral symptoms (verbally abusive, physically abusive, socially inappropriate
      or disruptive behavior) presented, and had reassessment of behavioral symptoms
      after 3 consecutive months of the initiated treatment. MEASUREMENTS: Behavioral
      symptom change was measured according to score (range 0-9, based on number and
      frequency of symptoms) change between baseline and reassessment (improved, <0;
      unchanged, 0; worsened, >0). Survival analyses were conducted on time to death
      after reassessment, comparing residents whose symptoms improved with those whose
      symptoms remained unchanged or worsened. RESULTS: APs and ADs were comparable in
      treatment effectiveness, as evidenced by more than 85% of the behavioral symptom
      episodes in each cohort improving or remaining stable. Mortality risk was lower
      in both cohorts (AP: adjusted hazard ratio (aHRAP ) = 0.93, 95% confidence
      interval (CI) = 0.81-1.07; AD: aHRAD = 0.82, 95% CI = 0.70-0.97) for residents
      whose symptoms improved than for those whose symptoms unchanged or worsened.
      CONCLUSION: ADs may be reasonable pharmacological alternatives to APs in clinical
      management of ADRD-related behavioral symptoms. Initial treatment response may
      alter medication-associated mortality risk. Further study is needed to confirm
      findings using other data and behavioral symptom-specific instruments.

PMID- 26310960
TI  - The Influence of Math Anxiety, Math Performance, Worry, and Test Anxiety on the
      Iowa Gambling Task and Balloon Analogue Risk Task.
AB  - Multiple studies have shown that performance on behavioral decision-making tasks,
      such as the Iowa Gambling Task (IGT) and Balloon Analogue Risk Task (BART), is
      influenced by external factors, such as mood. However, the research regarding the
      influence of worry is mixed, and no research has examined the effect of math or
      test anxiety on these tasks. The present study investigated the effects of
      anxiety (including math anxiety) and math performance on the IGT and BART in a
      sample of 137 undergraduate students. Math performance and worry were not
      correlated with performance on the IGT, and no variables were correlated with
      BART performance. Linear regressions indicated math anxiety, physiological
      anxiety, social concerns/stress, and test anxiety significantly predicted
      disadvantageous selections on the IGT during the transition from decision making
      under ambiguity to decision making under risk. Implications for clinical
      evaluation of decision making are discussed.

PMID- 26310961
TI  - Examination of a Bifactor Model of Obsessive-Compulsive Symptom Dimensions.
AB  - Although obsessive-compulsive (OC) symptoms are observed along four dimensions
      (contamination, responsibility for harm, order/symmetry, and unacceptable
      thoughts), the structure of the dimensions remains unclear. The current study
      evaluated a bifactor model of OC symptoms among those with and without obsessive
      compulsive disorder (OCD). The goals were (a) to evaluate if OC symptoms should
      be conceptualized as unidimensional or whether distinct dimensions should be
      interpreted and (b) to use structural equation modeling to examine the
      convergence of the OC dimensions above and beyond a general dimension with
      related criteria. Results revealed that a bifactor model fit the data well and
      that OC symptoms were influenced by a general dimension and by four dimensions.
      Measurement invariance of the bifactor model was also supported among those with
      and without OCD. However, the general OC dimension accounted for only half of the
      variability in OC symptoms, with the remaining variability accounted for by
      distinct dimensions. Despite evidence of multidimensionality, the dimensions were
      unreliable after covarying for the general OC dimension. However, the four
      dimensions did significantly converge with a latent OC spectrum factor above and
      beyond the general OC dimension. The implications of these findings for
      conceptualizing the structure of OCD are discussed.

PMID- 26310962
TI  - Increased mitochondrial ATP production capacity in brain of healthy mice and a
      mouse model of isolated complex I deficiency after isoflurane anesthesia.
AB  - We reported before that the minimal alveolar concentration (MAC) of isoflurane is
      decreased in complex I-deficient mice lacking the NDUFS4 subunit of the
      respiratory chain (RC) (1.55 and 0.81% at postnatal (PN) 22-25 days and 1.68 and
      0.65% at PN 31-34 days for wildtype (WT) and CI-deficient KO, respectively). A
      more severe respiratory depression was caused by 1.0 MAC isoflurane in KO mice
      (respiratory rate values of 86 and 45 at PN 22-25 days and 69 and 29 at PN 31-34
      days for anesthetized WT and KO, respectively). Here, we address the idea that
      isoflurane anesthesia causes a much larger decrease in brain mitochondrial ATP
      production in KO mice thus explaining their increased sensitivity to this
      anesthetic. Brains from WT and KO mice of the above study were removed
      immediately after MAC determination at PN 31-34 days and a mitochondria-enriched
      fraction was prepared. Aliquots were used for measurement of maximal ATP
      production in the presence of pyruvate, malate, ADP and creatine and, after
      freeze-thawing, the maximal activity of the individual RC complexes in the
      presence of complex-specific substrates. CI activity was dramatically decreased
      in KO, whereas ATP production was decreased by only 26% (p < 0.05). The
      activities of CII, CIII, and CIV were the same for WT and KO. Isoflurane
      anesthesia decreased the activity of CI by 30% (p < 0.001) in WT. In sharp
      contrast, it increased the activity of CII by 37% (p < 0.001) and 50% (p < 0.001)
      and that of CIII by 37% (p < 0.001) and 40% (p < 0.001) in WT and KO,
      respectively, whereas it tended to increase that of CIV in both WT and KO.
      Isoflurane anesthesia increased ATP production by 52 and 69% in WT (p < 0.05) and
      KO (p < 0.01), respectively. Together these findings indicate that isoflurane
      anesthesia interferes positively rather than negatively with the ability of CI
      deficient mice brain mitochondria to convert their main substrate pyruvate into
      ATP.

PMID- 26310963
TI  - Mannose receptor-mediated delivery of moss-made alpha-galactosidase A efficiently
      corrects enzyme deficiency in Fabry mice.
AB  - Enzyme replacement therapy (ERT) is an effective treatment for several lysosomal
      storage disorders (LSDs). Intravenously infused enzymes are taken up by tissues
      through either the mannose 6-phosphate receptor (M6PR) or the mannose receptor
      (MR). It is generally believed that M6PR-mediated endocytosis is a key mechanism
      for ERT in treating LSDs that affect the non-macrophage cells of visceral organs.
      However, the therapeutic efficacy of MR-mediated delivery of mannose-terminated
      enzymes in these diseases has not been fully evaluated. We tested the
      effectiveness of a non-phosphorylated alpha-galactosidase A produced from moss
      (referred to as moss-aGal) in vitro and in a mouse model of Fabry disease.
      Endocytosis of moss-aGal was MR-dependent. Compared to agalsidase alfa, a
      phosphorylated form of alpha-galactosidase A, moss-aGal was more preferentially
      targeted to the kidney. Cellular localization of moss-aGal and agalsidase alfa in
      the heart and kidney was essentially identical. A single injection of moss-aGal
      led to clearance of accumulated substrate in the heart and kidney to an extent
      comparable to that achieved by agalsidase alfa. This study suggested that mannose
      terminated enzymes may be sufficiently effective for some LSDs in which non
      macrophage cells are affected, and that M6P residues may not always be a
      prerequisite for ERT as previously considered. 

PMID- 26310964
TI  - Behavioural and emotional problems, intellectual impairment and health-related
      quality of life in patients with organic acidurias and urea cycle disorders.
AB  - BACKGROUND: Organic acidurias (OADs) and urea cycle disorders (UCDs) are inborn
      metabolic disorders with a risk for acute and chronic metabolic decompensation
      resulting in impairments of the central nervous system and other organ systems.
      So far, there is no systematic study of intellectual functioning,
      behavioural/emotional problems and health-related quality of life (HRQoL), and
      how these domains are connected. METHODS: Data of 152 patients with OADs (n =
      100) and UCDs (n = 52) from the European Registry and Network of intoxication
      type Metabolic Diseases (E-IMD) using standardized instruments were compared with
      normative data. RESULTS: Behavioural/emotional problems are increased in OADs or
      UCDs patients by a factor of 2.5 (3.0), in female asymptomatic carriers of X
      linked inherited UCD ornithine transcarbamylase deficiency (fasOTCD) by a factor
      of 1.5. All groups show similar patterns of behavioural/emotional problems, not
      different from epidemiological data. Mental disability (IQ <= 70) was found in
      31% of OAD, 43% of UCD, but not in fasOTCD subjects. HRQoL was decreased in the
      physical domain, but in the normal range. Behavioural/emotional problems were
      significantly associated with intellectual functioning (OR = 6.24, 95%CI: 1.39
      27.99), but HRQoL was independent from both variables. CONCLUSIONS: Patients with
      OADs and UCDs show increased frequencies of mental disability and
      behavioural/emotional problems. Profiles of behavioural/emotional problems were
      similar to epidemiological data. Intellectual disability and
      behavioural/emotional problems were strongly associated. Patients' HRQoL was in
      the normal range, possibly compensated by coping strategies of their families.
      Diagnostics and clinical care of OAD/UCD patients should be improved regarding
      behavioural/emotional, intellectual and quality of life aspects.

PMID- 26310965
TI  - Complex reference value distributions and partitioned reference intervals across
      the pediatric age range for 14 specialized biochemical markers in the CALIPER
      cohort of healthy community children and adolescents.
AB  - BACKGROUND: The CALIPER program has previously reported a comprehensive database
      of pediatric reference intervals for 63 biochemical and immunochemical markers.
      Here, covariate-stratified reference intervals were determined for a number of
      special assays not previously reported. METHODS: A total of 1917 healthy children
      and adolescents were recruited and serum concentrations of 14 biochemical markers
      were measured using the Abbott Architect ci4100 system. Age and gender partitions
      were statistically determined, outliers removed and reference intervals
      calculated using CSLI C28-A3 guidelines. RESULTS: Many analytes showed dynamic
      changes in concentration requiring at least 3 age partitions. Unique intervals
      were required within the first year of life for: pancreatic amylase, C-peptide,
      ceruloplasmin, insulin, beta-2-microglobulin, cystatin C, dehydroepiandrosterone
      sulfate (DHEA-S), and alpha-1-glycoprotein. Cholinesterase, cholinesterase
      dibucaine number, and immunoglobulin E required only 2 age partitions and alpha-1
      antitrypsin required only one. Anti-CCP and anti-TPO levels were below the
      detection limit of the assay. Some analytes including insulin and DHEA-S required
      additional gender partitions for specific age groups. CONCLUSIONS: Complex
      profiles were observed for endocrine and special chemistry markers, requiring
      establishment of age- and gender-specific reference intervals. These updated
      reference intervals will allow improved laboratory assessment of pediatric
      patients but should be validated for each analytical platform and local
      population as recommended by CLSI.

PMID- 26310966
TI  - Stress Response of Veterinary Students to Gynaecological Examination of Horse
      Mares - Effects of Simulator-Based and Animal-Based Training.
AB  - Invasive procedures in animals are challenging for veterinary students who may
      perceive a gynaecological examination of mares as stressful. Simulator-based
      training may reduce stress. In this study, students received equine gynaecology
      training 4 times either on horses (group H; n = 14) or a teaching simulator
      (group SIM; n = 13). One day and 14 days thereafter, their diagnostic skills were
      tested on horses (skills tests 1 and 2). During the skills tests, the students'
      stress response was analysed by heart rate, heart rate variability (HRV)
      parameters SDRR (standard deviation of beat-to-beat [RR] interval) and RMSSD
      (root-mean-square of successive RR differences), and salivary cortisol. In
      addition, students answered a questionnaire on their perceived stress.
      Sympathetic activation with increased heart rate (p < 0.001) occurred in both
      skills tests. In test 1, this increase was more pronounced in SIM than in H
      students (time * group p < 0.01). HRV decreased in students of both groups (p <
      0.001). In skills test 1, this decrease was more pronounced for SIM than for H
      students (between groups and time * group p < 0.01 for SDRR and p < 0.05 for
      RMSSD). High cortisol concentrations before the skills tests may indicate an
      anticipatory stress response. Subjective stress perception of students was higher
      in skills test 1 vs 2 (p < 0.01). In skills test 2, H students felt more stressed
      than SIM students (p < 0.01). Self-assessment thus differed from physiological
      stress parameters. In conclusion, gynaecological examination of mares evoked a
      moderate stress response in veterinary students, which was more evident after
      simulator-based than animal-based training. 

PMID- 26310967
TI  - Respiratory Tract Amyloidosis. State-of-the-Art Review with a Focus on Pulmonary
      Involvement.
AB  - Amyloidosis is a constellation of disease entities characterized by abnormal
      extracellular deposition and accumulation of protein and protein derivatives,
      which show apple-green birefringence when stained with Congo red and viewed under
      polarized light. Amyloid can infiltrate virtually all organ systems and can
      display multiple and diverse imaging findings. Pathologically, respiratory
      involvement occurs in 50 % of patients with amyloidosis, and its clinical signs
      and symptoms vary depending on whether the disease is systemic or localized. The
      four main patterns of respiratory tract involvement are tracheobronchial, nodular
      parenchymal, diffuse alveolar septal, and lymphatic. Imaging findings of
      amyloidosis are nonspecific and vary in each pattern; knowledge about the disease
      impairment type is thus very important, and amyloidosis should be considered in
      the differential diagnosis of other very common diseases, such as infectious
      diseases, neoplasms, and vasculitis. This literature review describes the main
      clinical and imaging manifestations of amyloidosis, focusing on respiratory tract
      involvement and differential diagnosis.

PMID- 26310968
TI  - A cost-effectiveness analysis of two different repositioning strategies for the
      prevention of pressure ulcers.
AB  - AIMS: To assess the cost effectiveness of two repositioning strategies and inform
      the 2014 National Institute for Health and Care Excellence clinical guideline
      recommendations on pressure ulcer prevention. BACKGROUND: Pressure ulcers are
      distressing events, caused when skin and underlying tissues are placed under
      pressure sufficient to impair blood supply. They can have a substantial impact on
      quality of life and have significant resource implications. Repositioning is a
      key prevention strategy, but can be resource intensive, leading to variation in
      practice. This economic analysis was conducted to identify the most cost
      effective repositioning strategy for the prevention of pressure ulcers. DESIGN:
      The economic analysis took the form of a cost-utility model. METHODS: The
      clinical inputs to the model were taken from a systematic review of clinical
      data. The population in the model was older people in a nursing home. The
      economic model was developed with members of the guideline development group and
      included costs borne by the UK National Health Service. Outcomes were expressed
      as costs and quality adjusted life years. CONCLUSION: Despite being marginally
      more clinically effective, alternating 2 and 4 hourly repositioning is not a cost
      effective use of UK National Health Service resources (compared with 4 hourly
      repositioning) for this high risk group of patients at a cost-effectiveness
      threshold of L20,000 per quality adjusted life years. These results were used to
      inform the clinical guideline recommendations for those who are at high risk of
      developing pressure ulcers.

PMID- 26310969
TI  - Epilepsy surgery in the United States: Analysis of data from the National
      Association of Epilepsy Centers.
AB  - OBJECTIVE: To examine trends in epilepsy-related surgical procedures performed at
      major epilepsy centers in the US between 2003 and 2012, and in the service
      provision infrastructure of epilepsy centers over the same time period. METHODS:
      We analyzed data from the National Association of Epilepsy Centers' (NAEC) annual
      surveys. The total annual figures, annual average figures per center and annual
      rates of each surgical procedure based on US population numbers for that year
      were calculated. Additional information on center infrastructure and manpower was
      also examined. RESULTS: The number of the NAEC's level 3 and level 4 epilepsy
      centers submitting annual survey reports increased from 37 centers in 2003 to 189
      centers in 2012. The average reported number of Epilepsy Monitoring Unit (EMU)
      beds per center increased from 7 beds in 2008 to 8 beds in 2012. Overall annual
      EMU admission rates doubled between 2008 and 2012 but the average number of EMU
      admissions and epilepsy surgeries performed per center declined over the same
      period. The annual rate of anterior temporal lobectomies (ATL) for mesial
      temporal sclerosis (MTS) declined by >65% between 2006 and 2010. The annual rate
      of extratemporal surgery exceeded that of ATL for MTS from 2008 onwards, doubled
      between 2007 and 2012 and comprised 38% of all resective surgeries in 2012. Vagus
      nerve stimulator implant rates consistently increased year on year and exceeded
      resective surgeries in 2011 and 2012. CONCLUSION: The last decade has seen a
      major change in the US epilepsy surgery landscape. Temporal lobectomies,
      particularly for MTS, have declined despite an increase in EMU admissions. On the
      other hands, case complexity correspondingly increased as evidenced by more
      extratemporal surgery, intracranial recordings and palliative procedures.

PMID- 26310970
TI  - Knowledge, attitude and behavioral determinants of tobacco use among 13-15 year
      old school children.
AB  - BACKGROUND: The epidemic of tobacco use is one of the greatest threats to global
      health today. Tobacco attributable deaths in India currently range from 800,000
      to 900,000 per year. Adolescents are among the most vulnerable group to start
      tobacco use. Information on tobacco use among the youth is necessary to establish
      control measures against it. OBJECTIVES: To assess the knowledge, attitude, and
      behavioral determinants of tobacco use among high school students (age13-15
      years) in Bangalore. MATERIALS AND METHOD: A cross-sectional study was conducted
      over a period of 3 weeks in the month of September 2012. A structured, pretested
      questionnaire was administered randomly to 500 high school students in Bangalore
      to assess the knowledge, attitude, and behavioral determinants of tobacco use.
      RESULTS: Majority of the study population [94.4% (472/500)] believed that smoking
      is definitely harmful to our health. Also, 39.0% of the participants of age 13
      years believed that smoking does not help in socializing and 92.2% of study
      subjects had negative attitude toward starting the habit. Most of them (83.9%)
      had a negative perception about smokers that they lack confidence. However, less
      than 1% of the study population had a habit of smoking at this young age.
      CONCLUSION: Awareness of the harmful effects of smoking was high among the study
      population. The study provides insight into the factors to consider while
      planning adolescent anti-smoking programs in this and similar settings.

PMID- 26310973
TI  - The Effect of Melatonin on Behavioral, Molecular, and Histopathological Changes
      in Cuprizone Model of Demyelination.
AB  - Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central
      nervous system. The protective effects of melatonin (MLT) on various
      neurodegenerative diseases, including MS, have been suggested. In the present
      study, we examined the effect of MLT on demyelination, apoptosis, inflammation,
      and behavioral dysfunctions in the cuprizone toxic model of demyelination.
      C57BL/6J mice were fed a chaw containing 0.2 % cuprizone for 5 weeks and received
      two doses of MLT (50 and 100 mg/kg) intraperitoneally for the last 7 days of
      cuprizone diet. Administration of MLT improved motor behavior deficits induced by
      cuprizone diet. MLT dose-dependently decreased the mean number of apoptotic cells
      via decreasing caspase-3 and Bax as well as increasing Bcl-2 levels. In addition,
      MLT significantly enhanced nuclear factor-kappaB activation and decreased heme
      oxygenase-1 level. However, MLT had no effect on interleukin-6 and myelin protein
      production. Our data revealed that MLT improved neurological deficits and
      enhanced cell survival but was not able to initiate myelin production in the
      cuprizone model of demyelination. These findings may be important for the design
      of potential MLT therapy in demyelinating disorders, such as MS.

PMID- 26310974
TI  - Solvent Effects on kp in Organic Media?: Statement to the Response.
AB  - A recent response on a publication from our team investigating solvent effects on
      propagation rate coefficients is commented. Among other issues, we point to the
      fact that the response interprets only a subset of the data provided in our
      original contribution. 

PMID- 26310972
TI  - Organotypic Spinal Cord Culture: a Proper Platform for the Functional Screening.
AB  - Recent improvements in organotypic slice culturing and its accompanying
      technological innovations have made this biological preparation increasingly
      useful ex vivo experimental model. Among organotypic slice cultures obtained from
      various central nervous regions, spinal cord slice culture is an absorbing model
      that represents several unique advantages over other current in vitro and in vivo
      models. The culture of developing spinal cord slices, as allows real-time
      observation of embryonic cells behaviors, is an instrumental platform for
      developmental investigation. Importantly, due to the ability of ex vivo models to
      recapitulate different aspects of corresponding in vivo conditions, these models
      have been subject of various manipulations to derive disease-relevant slice
      models. Moreover spinal cord slice cultures represent a potential platform for
      screening of different pharmacological agents and evaluation of cell
      transplantation and neuroregenerative materials. In this review, we will focus on
      studies carried out using the ex vivo model of spinal cord slice cultures and
      main advantages linked to practicality of these slices in both normal and
      neuropathological diseases and summarize them in different categories based on
      application.

PMID- 26310971
TI  - The Deleterious Effects of Oxidative and Nitrosative Stress on Palmitoylation,
      Membrane Lipid Rafts and Lipid-Based Cellular Signalling: New Drug Targets in
      Neuroimmune Disorders.
AB  - Oxidative and nitrosative stress (O&NS) is causatively implicated in the
      pathogenesis of Alzheimer's and Parkinson's disease, multiple sclerosis, chronic
      fatigue syndrome, schizophrenia and depression. Many of the consequences stemming
      from O&NS, including damage to proteins, lipids and DNA, are well known, whereas
      the effects of O&NS on lipoprotein-based cellular signalling involving
      palmitoylation and plasma membrane lipid rafts are less well documented. The aim
      of this narrative review is to discuss the mechanisms involved in lipid-based
      signalling, including palmitoylation, membrane/lipid raft (MLR) and n-3
      polyunsaturated fatty acid (PUFA) functions, the effects of O&NS processes on
      these processes and their role in the abovementioned diseases. S-palmitoylation
      is a post-translational modification, which regulates protein trafficking and
      association with the plasma membrane, protein subcellular location and functions.
      Palmitoylation and MRLs play a key role in neuronal functions, including
      glutamatergic neurotransmission, and immune-inflammatory responses.
      Palmitoylation, MLRs and n-3 PUFAs are vulnerable to the corruptive effects of
      O&NS. Chronic O&NS inhibits palmitoylation and causes profound changes in lipid
      membrane composition, e.g. n-3 PUFA depletion, increased membrane permeability
      and reduced fluidity, which together lead to disorders in intracellular signal
      transduction, receptor dysfunction and increased neurotoxicity. Disruption of
      lipid-based signalling is a source of the neuroimmune disorders involved in the
      pathophysiology of the abovementioned diseases. n-3 PUFA supplementation is a
      rational therapeutic approach targeting disruptions in lipid-based signalling.

PMID- 26310975
TI  - First-in-Man Dose-Escalation Study of the Selective BRAF Inhibitor RG7256 in
      Patients with BRAF V600-Mutated Advanced Solid Tumors.
AB  - BACKGROUND: BRAF mutations are a validated target for cancer therapy. A second
      generation BRAF inhibitor with an improved preclinical safety profile (RG7256)
      was evaluated in a first-in-man study in order to determine the safety, efficacy,
      pharmacokinetics and pharmacodynamics in patients with BRAF V600-mutated advanced
      solid tumors. PATIENTS AND METHODS: Patients received RG7256 orally over 8 dose
      levels from 200 mg once a day (QD) to 2400 mg twice a day (BID) (50-, 100- and
      150-mg tablets) using a classic 3 + 3 dose escalation design. RESULTS: In total,
      45 patients were enrolled; most (87 %) had advanced melanoma (94 % BRAF V600E).
      RG7256 was rapidly absorbed, with limited accumulation and dose-proportional
      increase in exposure up to 1950 mg BID. The maximal tolerated dose (MTD) was not
      reached. The most common drug-related adverse events (AEs) were dyspepsia (20 %),
      dry skin (18 %), rash (18 %), fatigue (16 %) and nausea (13 %), mainly grade 1.
      Three patients (7 %) developed cutaneous squamous cell carcinoma.
      Photosensitivity, arthralgia and increased liver enzyme levels were each observed
      in only one patient each. Of 44 evaluable patients, 14 (32 %) had a partial
      response (melanoma and thyroid cancer). At high dose levels (>1200 mg BID), 10 of
      16 (63 %) patients had a partial response. A decrease in maximum standardized
      uptake value (SUVmax) on FDG-PET of >=25 % was observed in 19 of 37 patients. On
      treatment reductions in pERK were documented in eight of ten paired tumor
      samples. CONCLUSIONS: RG7256 has a favorable safety profile compared to other
      BRAF inhibitors while maintaining clinical activity, and MTD was not reached. The
      excessive pill burden needed to provide the desired exposure, and thus concerns
      about patient compliance, limited further development of this agent. Study
      Identifier: ClinicalTrials.gov (NCT01143753).

PMID- 26310976
TI  - Effects of long-term ambient ozone exposure on biomass and wood traits in poplar
      treated with ethylenediurea (EDU).
AB  - This is the longest continuous experiment where ethylenediurea (EDU) was used to
      protect plants from ozone (O3). Effects of long-term ambient O3 exposure (23 ppm
      h AOT40) on biomass of an O3 sensitive poplar clone (Oxford) were examined after
      six years from in-ground planting. Trees were irrigated with either water or 450
      ppm EDU. Above (-51%) and below-ground biomass (-47%) was reduced by O3 although
      the effect was significant only for stem and coarse roots. Ambient O3 decreased
      diameter of the lower stem, and increased moisture content along the stem of not
      protected plants (+16%). No other change in the physical wood structure was
      observed. A comparison with a previous assessment in the same experiment
      suggested that O3 effects on biomass partitioning to above-ground organs depend
      on the tree ontogenetic stage. The root/shoot ratios did not change, suggesting
      that previous short-term observations of reduced allocation to tree roots may be
      overestimated. 

PMID- 26310977
TI  - Silver nanoparticle dissolution in the presence of ligands and of hydrogen
      peroxide.
AB  - Dissolution of silver nanoparticles (AgNP with carbonate or citrate coating,
      total Ag 1-5 MUM) was examined in the presence of the ligands cysteine, chloride
      and fulvic acids and of the oxidant hydrogen peroxide (H2O2) at low
      concentrations at pH 7.5. Dissolved Ag was separated from AgNP by
      ultrafiltration. Cysteine in the concentration range 0.2-5 MUM resulted in an
      initial increase of dissolved Ag within few hours. Chloride (up to 0.1 mM) and
      fulvic acids (up to 15 mg L(-1)) had little effect on the dissolution of AgNP
      within hours to days. In contrast, very rapid dissolution within 1-2 h of both
      carbonate and citrate coated AgNP was observed in the presence of H2O2 in the
      concentration range 0.1-10 MUM, under dark or light conditions. The high
      efficiency of H2O2 in dissolving AgNP is likely to be of importance in toxic
      effects of AgNP to algae, as H2O2 is produced and released into solution by
      algae. 

PMID- 26310978
TI  - Experimental determination of diagnostic window of cardiac troponins in the
      development of chronic anthracycline cardiotoxicity and estimation of its
      predictive value.
AB  - BACKGROUND: Cardiac troponins (cTns) seem to be more sensitive for the detection
      of anthracycline cardiotoxicity than the currently recommended method of
      monitoring LV systolic function. However, the optimal timing of blood sampling
      remains unknown. Hence, the aims of the present study were to determine the
      precise diagnostic window for cTns during the development of chronic
      anthracycline cardiotoxicity and to evaluate their predictive value. METHODS:
      Cardiotoxicity was induced in rabbits with daunorubicin (3mg/kg, weekly, for 8
      weeks). Blood samples were collected 2-168 h after the 1st, 5th and 8th drug
      administrations, and concentrations of cTns were determined using highly
      sensitive assays: hs cTnT (Roche) and hs cTnI (Abbott). RESULTS: The plasma
      levels of cTns progressively increased with the rising number of chemotherapy
      cycles. While only a mild non-significant increase in both cTn levels occurred
      after the first daunorubicin dose, a significant rise was observed after the 5th
      and 8th administrations. Two hours after these administrations, a significant
      increase occurred with a peak between 4-6h and a decline until 24h. Discrete cTn
      release continued even after cessation of the therapy. While greater variability
      of cTn levels was observed around the peak concentrations, the values did not
      correspond well with the severity of LV systolic dysfunction. Unlike AMI in
      cardiotoxicity, cTn elevations may be better associated with cumulative dose and
      concentrations at steady state than cmax. CONCLUSIONS: To the best of our
      knowledge, this is the first study to precisely describe the diagnostic window
      and predictive value of cTns in anthracycline cardiotoxicity.

PMID- 26310979
TI  - Cost-effectiveness of home versus clinic-based management of chronic heart
      failure: Extended follow-up of a pragmatic, multicentre randomized trial cohort -
      The WHICH? study (Which Heart Failure Intervention Is Most Cost-Effective &
      Consumer Friendly in Reducing Hospital Care).
AB  - OBJECTIVE: To assess the long-term cost-effectiveness of two multidisciplinary
      management programs for elderly patients hospitalized with chronic heart failure
      (CHF) and how it is influenced by patient characteristics. METHODS: A trial-based
      analysis was conducted alongside a randomized controlled trial of 280 elderly
      patients with CHF discharged to home from three Australian tertiary hospitals.
      Two interventions were compared: home-based intervention (HBI) that involved home
      visiting with community-based care versus specialized clinic-based intervention
      (CBI). Bootstrapped incremental cost-utility ratios were computed based on
      quality-adjusted life-years (QALYs) and total healthcare costs. Cost
      effectiveness acceptability curves were constructed based on incremental net
      monetary benefit (NMB). We performed multiple linear regression to explore which
      patient characteristics may impact patient-level NMB. RESULTS: During median
      follow-up of 3.2 years, HBI was associated with slightly higher QALYs (+0.26
      years per person; p=0.078) and lower total healthcare costs (AU$ -13,100 per
      person; p=0.025) mainly driven by significantly reduced duration of all-cause
      hospital stay (-10 days; p=0.006). At a willingness-to-pay threshold of AU$
      50,000 per additional QALY, the probability of HBI being better-valued was 96%
      and the incremental NMB of HBI was AU$ 24,342 (discounted, 5%). The variables
      associated with increased NMB were HBI (vs. CBI), lower Charlson Comorbidity
      Index, no hyponatremia, fewer months of HF, fewer prior HF admissions <1 year and
      a higher patient's self-care confidence. HBI's net benefit further increased in
      those with fewer comorbidities, a lower self-care confidence or no hyponatremia.
      CONCLUSIONS: Compared with CBI, HBI is likely to be cost-effective in elderly CHF
      patients with significant comorbidity.

PMID- 26310980
TI  - Jailed balloon protection and rescue balloon jailing techniques set the field for
      safer bifurcation provisional stenting.

PMID- 26310981
TI  - Mickey Mouse in the cath lab.

PMID- 26310982
TI  - Improve-it: Full disclosures?

PMID- 26310983
TI  - Ventricular tachycardia associated with mid-ventricular obstructive hypertrophic
      cardiomyopathy and apical aneurysm.

PMID- 26310984
TI  - Intrathecal fentanyl blockade of afferent neural feedback from skeletal muscle
      during exercise in heart failure patients: Influence on circulatory power and
      pulmonary vascular capacitance.
AB  - BACKGROUND: Secondary pulmonary hypertension is common in heart failure (HF)
      patients. We hypothesized that inhibition of feedback from locomotor muscle group
      III/IV neurons contributes to reduced pulmonary vascular pressures independent of
      changes in cardiac function during exercise in HF. METHODS: 9 HF patients (ages,
      60 +/- 2; EF, 26.7 +/- 1.9%; New York Heart Association classes, I-III) and 9
      age/gender matched controls (ages, 63 +/- 2) completed five-minutes of constant
      load cycling (65% Workloadpeak) with intrathecal fentanyl or placebo on
      randomized separate days. Mean arterial pressure (MAP), heart rate (HR), end
      tidal partial pressure of CO2 (PETCO2), and oxygen consumption (VO2) were
      measured at rest and exercise. Non-invasive surrogates for cardiac power
      (circulatory power, CircP=VO2 * MAP), stroke volume (oxygen pulse,
      O2pulse=VO2/HR), and pulmonary arterial pressure (GXCAP=O2pulse * PETCO2) were
      calculated. RESULTS: At rest and end-exercise, differences between fentanyl
      versus placebo were not significant for CircP in HF or controls. Differences
      between fentanyl versus placebo for GXCAP were not significant at rest in HF or
      controls. At end-exercise, GXCAP was significantly higher with fentanyl versus
      placebo in HF (691 +/- 59 versus 549 +/- 38 mL/beat * mmHg), but not controls
      (536 +/- 59 versus 474 +/- 43 mL/beat * mmHg). Slopes (rest to end-exercise) for
      GXCAP were significantly higher with fentanyl versus placebo in HF (95.1 +/- 9.8
      versus 71.6 +/- 6.0 mL/beat * mmHg), but not controls (74.3 +/- 9.5 versus 60.8
      +/- 6.5 mL/beat * mmHg). CircP slopes did not differ between fentanyl versus
      placebo in HF or controls (p>0.05). CONCLUSION: We conclude that feedback from
      locomotor muscle group III/IV neurons may evoke increases in pulmonary vascular
      pressures independent of changes in cardiac function during exercise in HF.

PMID- 26310985
TI  - Plasma immature form of surfactant protein type B correlates with prognosis in
      patients with chronic heart failure. A pilot single-center prospective study.
AB  - BACKGROUND: Gas exchange abnormalities are part of the heart failure (HF)
      syndrome and growing interest raised on possible biomarkers of alveolar-capillary
      unit damage. The present pilot single-center study sought to investigate the
      prognostic values of circulating surfactant protein type B (SP-B) in a cohort of
      systolic HF patients. METHODS: One hundred and fifty-one HF stable outpatients
      and 37 healthy subjects underwent a full clinical assessment, including pulmonary
      function and lung diffusion for carbon monoxide (DLco), maximal cardiopulmonary
      exercise test and measurements for both circulating immature and mature forms of
      SP-B. Study end-points were hospitalization due to HF worsening and
      cardiovascular mortality. RESULTS: Immature SP-B, but not the mature form, was
      significantly higher in HF patients than in controls and was independently
      related to DLco, peak oxygen uptake and ventilatory efficiency. During the follow
      up (median: 995 days; interquartile range: 739-1247 days), 97 patients
      experimented at least one HF hospitalization and 9 died for cardiovascular
      causes. At univariate analysis immature SP-B levels were significantly related to
      both cardiovascular death (p=0.033) and HF hospitalization (p<0.001). At
      multivariate analysis, immature SP-B levels remained independently associated to
      HF hospitalization (hazard ratio: 2.304; 95% confidence interval 1.858-3.019;
      p<0.001). CONCLUSIONS: Present data confirm a strong relationship between
      circulating immature SP-B levels, gas exchange abnormalities and exercise
      limitations in stable HF as well as they are consistent with the use of immature
      SP-B in HF clinical risk assessment. Larger prospective studies are needed to
      confirm its prognostic role as well as to evaluate whether immature SP-B plasma
      concentration varies in response to specific treatment.

PMID- 26310986
TI  - Bicuspid aortic valve aortopathy in adults: Incidence, etiology, and clinical
      significance.
AB  - Bicuspid aortic valve is the most common congenital heart defect and is
      associated with an aortopathy manifested by dilatation of the ascending thoracic
      aorta. The clinical consequences of this aortopathy are the need for periodic
      monitoring of aortic diameters, elective prophylactic surgical aortic repair, and
      the occurrence of aortic dissection or rupture. This review describes the current
      knowledge of BAV aortopathy in adults, including incidence, pathophysiologic
      insights into its etiology, contemporary hypothesis-generating observations into
      its complications, and recommendations for monitoring and intervention. 

PMID- 26310987
TI  - Mechanistic link between nonalcoholic fatty liver disease and cardiometabolic
      disorders.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a chronic condition characterized by
      fat accumulation combined with low-grade inflammation in the liver. A large body
      of clinical and experimental data shows that increased flux of free fatty acids
      from increased visceral adipose tissue can lead to NAFLD related with insulin
      resistance. Thus, individuals with obesity, insulin resistance, and dyslipidemia
      are at the greatest risk of developing NAFLD. Conversely, NAFLD is one of the
      phenotypes of insulin resistance or metabolic syndrome. Many researchers have
      discovered a close association between NAFLD and insulin resistance, and focused
      on the role of NAFLD in the development of type 2 diabetes. Further, substantial
      evidence has suggested the association between NAFLD and cardiovascular disease
      (CVD). In the current review, we provide a plausible mechanistic link between
      NAFLD and CVD and the potential of the former as a therapeutic target based on
      pathophysiology. We also discuss in detail about the role of insulin resistance,
      oxidative stress, low-grade inflammation, abnormal lipid metabolism, gut
      microbiota, changes of biomarkers, and genetic predisposition in the pathological
      linking between NAFLD and cardiometabolic disorders. 

PMID- 26310988
TI  - Vagal atrial fibrillation: What is it and should we treat it?
AB  - Vagal atrial fibrillation (AF) remains an under-recognised entity, affecting
      younger patients often with structurally normal hearts. Although there remains no
      universal definition or diagnostic criteria, in this review we describe
      recognised triggers and associated features, including a well-established
      association with athletic training. We explore potential mechanisms, including
      the role of the autonomic nervous system and ganglionated plexi in initiating and
      maintaining arrhythmia. We discuss the limited evidence base addressing the
      question of progression to persistent AF, and debate the merits of anti
      arrhythmic treatment, as well as uncertainty regarding the risk of stroke.
      Differences in suggested pharmacological therapy are highlighted and as is the
      emerging promise of radiofrequency catheter ablation as a therapeutic option. As
      we recognise the emerging burden of vagal AF, we hope to explore the important
      similarities and differences crucial to developing our understanding of the
      disorder, and highlight some significant questions which remain unanswered. 

PMID- 26310989
TI  - How firm is the evidence for miniaturized extracorporeal circulation versus
      conventional cardiopulmonary bypass for coronary revascularization? A trial
      sequential analysis.

PMID- 26310990
TI  - mRNA-Producing Pseudo-nucleus System.
AB  - A pseudo-eukaryotic nucleus (PEN) system consisting of a gene-containing DNA
      hydrogel encapsulated in a liposome is fabricated. Owing to the structural
      characteristics of gene-containing DNA hydrogel, mRNA transcription efficiency is
      promoted 2.57-fold. Through the use of PEN as a platform for mRNA delivery to the
      cytosol, prolonged protein translation is achieved. 

PMID- 26310991
TI  - Restrictive eating in anorexia nervosa: Examining maintenance and consequences in
      the natural environment.
AB  - OBJECTIVE: This study examined negative and positive affect in relation to
      restrictive eating episodes (i.e., meals/snacks perceived as restrictive) and
      whether restrictive eating was associated with likelihood of subsequent eating
      disorder behaviors (i.e., additional restrictive eating, binge eating, vomiting,
      laxative use, weighing, exercising, meal skipping, drinking fluids to curb
      appetite, body checking). METHOD: Women with anorexia nervosa (N = 118) completed
      a 2-week ecological momentary assessment protocol. RESULTS: For both restrictive
      and nonrestrictive eating, negative affect significantly increased from
      prebehavior to the time of the behavior but remained stable thereafter, while
      positive affect remained stable from prebehavior to the time of the behavior but
      decreased significantly thereafter. Across time, negative affect was
      significantly lower and positive affect was significantly greater in restrictive
      than nonrestrictive episodes. Engagement in restrictive eating was associated
      with an increased likelihood of subsequent restrictive eating, laxative use, and
      body checking, but not other behaviors. Engagement in nonrestrictive eating was
      associated with a decreased likelihood of subsequent restrictive eating, binge
      eating, vomiting, laxative use, weighing, meal skipping, drinking fluids to curb
      appetite, and body checking. DISCUSSION: Despite similar patterns of affect
      across eating episodes over time, results suggest affect may be involved in the
      maintenance of restrictive eating in anorexia nervosa since restrictive episodes
      were associated with lower negative and greater positive affect across time
      compared to nonrestrictive episodes. Further, while restrictive episodes
      increased the likelihood of only three subsequent eating disorder behaviors,
      nonrestrictive episodes were protective since they decreased likelihood of all
      but one behavior.

PMID- 26310992
TI  - Two Peptides from Soy beta-Conglycinin Induce a Hypocholesterolemic Effect in
      HepG2 Cells by a Statin-Like Mechanism: Comparative in Vitro and in Silico
      Modeling Studies.
AB  - Two peptides from soybean beta-conglycinin, i.e., YVVNPDNDEN (peptide 2) and
      YVVNPDNNEN (peptide 3), are known to be absorbed by human enterocytes. The former
      is a fragment of LRVPAGTTFYVVNPDNDENLRMIA (peptide 1), previously shown to
      increase the low-density lipoprotein (LDL) uptake and degradation in hepatocytes.
      Research carried out in silico on their interactions with the catalytic site of 3
      hydroxy-3-methylglutaryl CoA reductase (HMGCoAR) demonstrated that they behave as
      competitive inhibitors of HMGCoAR activity with a statin-like mechanism,
      confirmed by direct inhibition experiments. Research in HepG2 cells aimed at
      investigating the effects of these peptides on cholesterol metabolism showed that
      compared to mock treatment peptide 2 at 350 MUM up-regulates the mature SREBP2
      protein level by 134.0 +/- 10.5%, increases the LDLR protein level by 152.0 +/-
      20.0%, and enhances the HMGCoAR protein production by 171 +/- 29.9%, whereas
      peptide 3 up-regulates the mature SREBP2 protein level by 158.0 +/- 9.2%,
      increases the LDL level 164.0 +/- 17.9%, and induces a HMGCoAR protein increase
      by 170 +/- 50.0%. 

PMID- 26310993
TI  - Updated cannulation technique for tissue plasminogen activator injection into
      peripapillary retinal vein for central retinal vein occlusion.
AB  - PURPOSE: To update the surgical technique in which a vitrectomy is performed and
      a retinal branch vein is cannulated and infused with recombinant tissue
      plasminogen activator (RTPA) to treat central retinal vein occlusion (CRVO) in
      patients who present with very low visual acuity (VA). METHODS: Twelve
      consecutive patients (12 eyes) with CRVO and low VA (logMAR >1.00) at
      presentation were treated using this method. RESULTS: Cannulation of a
      peripapillary retinal vein and stable injection of RTPA was successfully
      performed without surgery-related complications in all 12 eyes. At 12 months
      after surgery, 8 of the 12 patients (67%) experienced at least one line of
      improvement in best corrected visual acuity; 6 of the 12 (50%) improved >=5 lines
      and 2 (17%) improved >=8 lines. After additional grid laser and/or
      subconjunctival or intravitreal corticosteroids, the mean decrease in central
      foveal thickness was 260 MUm, and the mean total macular volume decreased from
      12.10 mm(3) to 9.24 mm(3) . Four patients received panretinal photocoagulation to
      treat either iris neovascularization (n = 2) or neovascularization of the retina
      and/or disc (n = 2). CONCLUSION: Administration of RTPA via a peripapillary vein
      using this updated technique provides an alternative or additional treatment
      option for patients with very low VA after CRVO.

PMID- 26310994
TI  - Effect of different hand positions on trunk and shoulder kinematics and reaction
      forces in sitting pivot transfer.
AB  - [Purpose] The purpose of this study was to compare the changes in trunk and
      shoulder angles, and reaction forces under the two hands elicited by different
      hand base of support positions during sitting pivot transfer. [Subjects and
      Methods] Eighteen unimpaired subjects performed independent sitting pivot
      transfer. Subjects performed sitting pivot transfer between an initial seat to a
      target seat by only using their hands positioned at the same height as and lower
      than the seat position. Trunk and shoulder kinematics, and reaction forces on the
      trailing and leading hands were calculated. Mean peak joint angles and forces
      were compared between the hand positions using the pared t-test for the lift
      phase of the transfer. [Results] There were significant increases in the trunk
      angles of forward and lateral flexion, even though rotation decreased while
      transferring in the lower hand position. Increased shoulder flexion,
      anterior/posterior forces and reduced lateral forces were also shown.
      [Conclusion] Placing the hands of the supporting arms lower than the seat
      position during sitting pivot transfer was identified as having biomechanical
      advantages. Therefore, the lower hand position can be recommended as an effective
      and safe method for sitting pivot transfer by patients with spinal cord injury
      and can be utilized as a reference data for considering the appropriate height of
      aids for a wheelchair. 

PMID- 26310995
TI  - Lipid-bilayer-assisted two-dimensional self-assembly of DNA origami
      nanostructures.
AB  - Self-assembly is a ubiquitous approach to the design and fabrication of novel
      supermolecular architectures. Here we report a strategy termed 'lipid-bilayer
      assisted self-assembly' that is used to assemble DNA origami nanostructures into
      two-dimensional lattices. DNA origami structures are electrostatically adsorbed
      onto a mica-supported zwitterionic lipid bilayer in the presence of divalent
      cations. We demonstrate that the bilayer-adsorbed origami units are mobile on the
      surface and self-assembled into large micrometre-sized lattices in their lateral
      dimensions. Using high-speed atomic force microscopy imaging, a variety of
      dynamic processes involved in the formation of the lattice, such as fusion,
      reorganization and defect filling, are successfully visualized. The surface
      modifiability of the assembled lattice is also demonstrated by in situ decoration
      with streptavidin molecules. Our approach provides a new strategy for preparing
      versatile scaffolds for nanofabrication and paves the way for organizing
      functional nanodevices in a micrometer space. 

PMID- 26310996
TI  - Alphavirus-based vaccines in melanoma: rationale and potential improvements in
      immunotherapeutic combinations.
AB  - Immune checkpoint blockade has formally demonstrated the clinical benefit of
      immunotherapy against melanoma. New immunotherapeutic modalities are currently
      explored to improve the management of relapsing/refractory patients. Potent
      antitumor vaccines would have the advantage to promote long-lasting tumor control
      while limiting autoimmunity. Alphavirus vectors and nonreplicating particles
      offer versatile platforms to deliver antigen expression and immunize against
      cancer. They have shown promising preclinical results and initial proof of
      clinical activity in melanoma. The growing number of clinically available
      immunomodulatory agents provides a tremendous opportunity to exploit and revisit
      anticancer vaccines in the setting of powerful immunotherapeutic combinations.
      Accelerating the evaluation of alphavirus-based vaccines in patients with immune
      sensitive, but still very deadly malignancies, such as melanoma, is thus
      extremely important. 

PMID- 26310997
TI  - Preferred Presentation of the Visual Analog Scale for Measurement of
      Postoperative Pain.
AB  - BACKGROUND: The aim of this study was to evaluate differences in pain scores with
      different visual analog scale (VAS) presentations and to compare those
      differences with a numeric rating scale. We also asked the patients for
      preference of the different methods. METHODS: Prior to the trial, we performed
      power calculations to estimate a preferred sample size, and 62 postoperative
      patients supplied a complete set of data to the study. Inclusion criteria were
      newly operated patients within the first 5 days after surgery. Every patient
      included was with 1-minute intervals and presented with one of the following 100
      mm VAS lines: VAS horizontal with or without stop lines at the endings, or VAS
      vertical with or without stop lines. They also completed a numeric rating scale
      (NRS). RESULTS: We did not find differences in pain scores between the four VAS
      measures. The NRS had slightly higher pain scores than VAS, especially at low
      levels of pain. Patients preferred the NRS as compared to the VAS, and when
      choosing between the four different VAS presentations, they preferred the
      horizontal VAS with stop lines at the ends. CONCLUSION: For daily clinical
      practice for guiding postoperative analgesic treatment, the NRS seems to be a
      good option measuring pain reliably with good patient understanding and
      acceptance. For pain research, where there may be more time to explain the method
      and when a scale with more data points may be preferred, a VAS horizontal
      including stop lines at the ends can be recommended.

PMID- 26310998
TI  - Siliceous spicules enhance fracture-resistance and stiffness of pre-colonial
      Amazonian ceramics.
AB  - Pottery was a traditional art and technology form in pre-colonial Amazonian
      civilizations, widely used for cultural expression objects, utensils and as
      cooking vessels. Abundance and workability of clay made it an excellent choice.
      However, inferior mechanical properties constrained their functionality and
      durability. The inclusion of reinforcement particles is a possible route to
      improve its resistance to mechanical and thermal damage. The Amazonian
      civilizations incorporated freshwater tree sponge spicules (cauixi) into the clay
      presumably to prevent shrinkage and crack propagation during drying, firing and
      cooking. Here we show that isolated siliceous spicules are almost defect-free
      glass fibres with exceptional mechanical stability. After firing, the spicule
      Young's modulus increases (from 28 +/- 5 GPa to 46 +/- 8 GPa) inferring a
      toughness increment. Laboratory-fabricated ceramic models containing different
      inclusions (sand, glass-fibres, sponge spicules) show that mutually-oriented
      siliceous spicule inclusions prevent shrinkage and crack propagation leading to
      high stiffness clays (E = 836 +/- 3 MPa). Pre-colonial amazonian potters were the
      first civilization known to employ biological materials to generate composite
      materials with enhanced fracture resistance and high stiffness in the history of
      mankind. 

PMID- 26310999
TI  - Images of pheochromocytoma in adrenal glands.
AB  - Pheochromocytomas are relatively rare tumors of the adrenal medulla. A wide
      spectrum of imaging findings has been described. The aim of this article is to
      describe the multimodality imaging features of pheochromocytomas including
      diagnostic pearls that can help differentiate them from other adrenal lesions and
      pitfalls to avoid. 

PMID- 26311001
TI  - Comparison of Environmental MRSA Levels on High-Touch Surfaces in Contact
      Isolation and Noncontact Isolation Patient Rooms.
AB  - Environmental samples were collected from 100 hospital rooms, 32 noncontact
      rooms, and 68 contact isolation rooms. We isolated 202 and 1,830 MRSA colonies in
      noncontact and contact isolation rooms, respectively. The study identified MRSA
      isolates in hospital rooms of patients without colonization or infection with
      MRSA. Infect. Control Hosp. Epidemiol. 2015;36(12):1472-1475. 

PMID- 26311000
TI  - Zygote intrafallopian tube transfer versus intrauterine cleavage or blastocyst
      stage transfer after intracytoplasmic sperm injection cycles in patients with
      repeated implantation failure: A prospective follow-up study.
AB  - AIM: This study aimed to compare the outcomes between zygote intrafallopian
      transfer (ZIFT) with intrauterine day-3 (cleavage stage) embryo transfer and
      intrauterine day-5 (blastocyst stage) embryo transfer in patients undergoing
      intracytoplasmic sperm injection. MATERIAL AND METHODS: This prospective study
      was performed at Royan Institute, Tehran, Iran, between January 2012 and January
      2014. Two hundred fifty women with more than three unexplained implantation
      failures were divided non-randomly into three groups according to embryonic age
      and methods used as follows: (i) intrauterine cleavage-stage embryo transfer (n =
      100); (ii) intrauterine blastocyst-stage embryo transfer (n = 50); and (iii) ZIFT
      (n = 100). Implantation, clinical pregnancy, miscarriage and live birth rates
      were our main outcomes. RESULTS: Patients' characteristics and ovarian response
      were comparable among the three groups. Implantation rate (56.1% vs 27.9%) was
      significantly higher in the blastocyst group as compared to the ZIFT group;
      however, clinical pregnancy rate (38% vs 23%) was not statistically significantly
      different between the two groups, but due to the significantly higher miscarriage
      rate (34.7% vs 5.3%) in the ZIFT group, the live birth rate was significantly
      higher in the blastocyst group (P = 0.04). No significant differences were found
      between the cleavage-stage and blastocyst-stage groups in terms of implantation,
      clinical pregnancy, miscarriage and live birth rates. CONCLUSION: We do not
      recommend the use of the ZIFT procedure for patients with repeated implantation
      failures. It seems that replication of cleavage- or blastocyst-stage embryo
      transfer is more efficient and affordable.

PMID- 26311002
TI  - Differential effects of protein phosphatases in the recycling of metabotropic
      glutamate receptor 5.
AB  - The major excitatory neurotransmitter Glutamate acts on both ionotropic and
      metabotropic glutamate receptors (mGluRs) in the central nervous system. mGluR5,
      a member of the group I mGluR family is widely expressed throughout the brain and
      plays important roles in a variety of neuronal processes including various forms
      of synaptic plasticity. This receptor is also involved in various
      neuropsychiatric disorders, viz., Fragile X syndrome, autism etc. It has been
      reported that mGluR5 undergoes desensitization and subsequently internalization
      on ligand exposure in various cell types. However, the downstream events after
      the internalization and the molecular players involved in the post-endocytic
      events of this receptor have not been studied. In the present study, we find that
      subsequent to internalization mGluR5 enters the recycling compartment. After that
      the receptor recycles back to the cell surface. We also show here that the
      recycling of mGluR5 is dependent on protein phosphatases. Our data suggest that
      mGluR5 recycling is completely dependent on the activity of PP2A whereas, PP2B
      has partial effect on this process. Thus our study suggests that mGluR5 recycles
      back to the cell surface after ligand-dependent internalization and protein
      phosphatases that have been implicated in various forms of synaptic plasticity
      have differential effects on the recycling of mGluR5. 

PMID- 26311003
TI  - Effects of CB1 receptor agonism and antagonism on behavioral fear and
      physiological stress responses in adult intact, ovariectomized, and estradiol
      replaced female rats.
AB  - There is growing interest in the development of cannabis-based therapies for the
      treatment of fear and anxiety disorders. There are a few studies, but none in
      females, of the effects of the highly selective cannabinoid receptor type 1 (CB1)
      agonist, arachidonyl 2'-chlorethylamide (ACEA), on behavioral fear. In experiment
      1 involving gonadally-intact females, ACEA (either 0.1 or 0.01 mg/kg) was without
      effect in the elevated plus maze (EPM), and the lower dose decreased anxiety in
      the open field test (OFT). AM251 increased anxiety in the EPM and decreased
      locomotor activity in the OFT. Twenty-four hours after fear conditioning, neither
      ACEA nor AM251 affected generalized fear or conditioned fear recall. AM251 and
      0.1 mg/kg ACEA impaired, and 0.01 mg/kg ACEA enhanced, within-session fear
      extinction. AM251 increased plasma corticosterone concentrations after the fear
      extinction session, whereas ACEA was without effect. Based on evidence that
      estradiol may moderate the effects of CB1 receptor signaling in females,
      experiment 2 involved ovariectomized (OVX) rats provided with 10-MUg 17beta
      Estradiol and compared with OVX rats without hormone replacement (oil vehicle).
      Irrespective of hormone treatment, AM251 increased anxiety in the EPM, whereas
      ACEA (0.01 mg/kg) was without effect. Neither hormone nor drug altered anxiety in
      the OFT, but estradiol increased and AM251 decreased distance traveled. After
      fear conditioning, AM251 decreased generalized fear. Neither hormone nor drug had
      any effect on recall or extinction of conditioned fear, however, ACEA and AM251
      increased fear-induced plasma corticosterone concentrations. Further, when
      results with intact rats were compared with those from OVX rats, gonadal status
      did not moderate the effects of either AM251 or ACEA, although OVX displayed
      greater anxiety and fear than did intact rats. Thus, the effects of CB1 receptor
      antagonism and agonism in adult female rats do not depend on ovarian estradiol.

PMID- 26311004
TI  - Impact of traumatic dental injury on the quality of life of young children: a
      case-control study.
AB  - There are no longitudinal studies that assess the impact of traumatic dental
      injury (TDI) on the oral health-related quality of life (OHRQoL) of preschool
      children. To investigate the impact of TDI on OHRQoL among preschool children, a
      population-based case-control study was carried out with a representative sample
      of 335 children, 3-5 years of age, enrolled at public and private preschools in
      the city of Campina Grande, Brazil. The case group and the control group were
      matched for age, gender, type of preschool and monthly household income at a
      ratio of 1:4 (67 cases and 286 controls). Impact on the OHRQoL of children was
      assessed through administration of the Early Childhood Oral Health Impact Scale
      (ECOHIS). The occurrence of TDI was determined through clinical examinations
      performed by three calibrated dentists. Data analysis involved descriptive
      statistics, McNemar's test, the chi-square test with linear trend and conditional
      logistic regression analysis [P<=0.05; 95% confidence interval (95% CI)]. The
      most frequent responses were 'felt pain' (19.4%) and 'difficulty eating' (16.4%).
      The prevalence of TDI was 37.3% in the case group and 33.9% in the control group.
      No statistically significant differences were found between case and control
      groups regarding the presence of TDI (odds ratio=1.16; 95% CI: 0.66-2.02). TDI
      had no impact on the quality of life of preschool children.

PMID- 26311005
TI  - Muscle sparing thoracotomy for esophageal cancer: a comparison with
      posterolateral thoracotomy.
AB  - PURPOSE: The aim of this study was to investigate whether muscle sparing
      thoracotomy (MST) improved postoperative chest pain and an impairment of the
      postoperative pulmonary function in comparison with posterolateral thoracotomy
      (PLT). METHODS: Twenty-four patients with esophageal cancer who underwent PLT
      from September 2006 to August 2008 and 30 patients who underwent MST from
      September 2008 to August 2010 were selected as subjects of this study.
      Postoperative acute and chronic chest pain and the recovery of the pulmonary
      function were retrospectively compared between the two groups. RESULTS: The
      frequency of the additional use of analgesics was on days 3, 6, and 7 (mean 0.4
      vs. 1.2, p = 0.027, 0.4 vs. 1.5, p = 0.007, and 0.2 vs. 1.2, p = 0.009,
      respectively) in the early postoperative period. The number of patients requiring
      analgesics at 1 and 3 months after surgery was significantly lower in the MST
      group than in the PLT group (13.3 vs. 58.3 %, p = 0.002, 10.0 vs. 50.0 %, p =
      0.001, respectively). The postoperative vital capacity, expressed as a percentage
      of the preoperative value, 3 and 12 months after surgery was significantly higher
      in the MST group than in the PLT group (86.0 vs. 73.8 %, p = 0.028, 93.2 vs. 76.9
      %, p = 0.002, respectively). CONCLUSION: Compared with PLT, MST might, therefore,
      reduce postoperative chest pain and offer a better recovery of pulmonary function
      in patients with esophageal cancer.

PMID- 26311006
TI  - Idiopathic pseudoaneurysm: a rare cause of parotid mass.
AB  - A 77-year-old woman presented with a pulsatile blue-tinged mass over the left
      parotid, present for 5 years, and slowly enlarging. The size of the mass
      fluctuated during this period and there was no associated pain. The patient
      reported no history of surgery or trauma. Vascular lesions are rarely encountered
      within parotid glands in adults. MRI with contrast demonstrated a soft tissue
      lesion; despite the presence of feeding vessels it was thought unlikely to be an
      arterial venous malformation or aneurysmal change. The appearance was thought to
      be in keeping with an enlarged lymph node or sebaceous cyst. Fine-needle
      aspiration was obtained using ultrasound guidance and yielded bloody fluid. The
      lesion was closely related to the superficial temporal artery and a diagnosis of
      a thrombosed pseudoaneurysm was made. The vessel had thrombosed and the decision
      was made to enact a watchful waiting policy. The patient will be monitored in the
      outpatient setting. 

PMID- 26311007
TI  - Successful acute and late management of a chemical burn with primary implantation
      of Boston type 1 keratoprosthesis.
AB  - A 29-year-old woman presented to our clinic 1 month after an accidental chemical
      burn with concentrated sulfuric acid, involving her entire face including eyes
      and neck. She received treatment for her ocular and facial burns, and
      subsequently underwent Boston type 1 keratoprosthesis in her right eye after 1
      year. One week postoperatively, she was diagnosed with advanced disc damage, and
      was started on topical antiglaucoma medication. Visual field testing was only
      possible at 2 months postoperative, once visual acuity improved. Subsequently,
      progression of visual field defect was noted on Humphrey visual field 10-2,
      needing implantation of an Ahmed glaucoma valve in her right eye. Two years after
      the Boston type 1 keratoprosthesis implantation, the patient's best-corrected
      visual acuity was stable at 20/100; intraocular pressure was digitally normal
      with a stable visual field. 

PMID- 26311008
TI  - Fatal Pneumocystis jirovecii pneumonia in a HIV-negative adult.
AB  - Pneumocystis jirovecii is responsible for P. jirovecii pneumonia (PJP) in
      immunocompromised individuals, with a recent rise of cases noted in non-HIV
      patients. A middle-aged man presented with new-onset cough, fever, hypoxia and
      tachypnoea. He was on a tapering course of dexamethasone for amiodarone-induced
      thyrotoxicosis. He developed worsening airspace disease necessitating mechanical
      ventilation. Bronchoalveolar lavage (BAL) fluid was positive for P. jirovecii and
      he was managed with trimethoprim/sulfamethoxazole and pentamidine, but succumbed
      to cardiorespiratory arrest. One-third of PJP cases occur in non-HIV patients,
      and have a higher morbidity and mortality. Most immunocompromised patients
      typically exhibit PJP during a corticosteroid taper. The accurate dose, duration
      or frequency of steroid use in not well established. Diagnosis of PJP in this
      population is more challenging due to lower BAL yield with alternate modalities
      such as serum/BAL beta-d-glucan and PCR enhancing the yield. Further studies are
      needed to highlight PJP prophylaxis in patients with steroid use. 

PMID- 26311009
TI  - Nodular mucinosis misdiagnosed as non-responsive secondary syphilis.
AB  - A previously healthy 24-year-old man presented with an erythematous, non-pruritic
      and painless papulonodular skin rash affecting the trunk, upper arms (excluding
      palms), neck, face, forehead and scalp. He had a penile ulcer for the past 2
      weeks, almost healed at the time of observation. The patient tested positive for
      syphilis and HIV-1; he claimed being negative for HIV 6 months earlier. As the
      palms were not affected, we performed a skin biopsy for the differential
      diagnosis between secondary lues and acute HIV seroconversion reaction.
      Benzathine penicillin (2,400,000 units) was administrated and antiretroviral
      therapy started. Although the skin biopsy was compatible with secondary syphilis,
      there was no change in the skin rash 3 weeks after the first penicillin
      administration. Another 2 doses of penicillin were given but 4 weeks later the
      rash persisted. A second biopsy revealed a mucinous skin infiltration, compatible
      with nodular mucinosis.

PMID- 26311010
TI  - Levamisole-contaminated cocaine: a hairy affair.
AB  - Levamisole-contaminated cocaine can induce severe systemic vasculitis. The
      diagnosis can be challenging, especially when substance abuse is uncertain. We
      present the case of a 42-year-old woman suffering from vasculitis due to
      levamisole-contaminated cocaine, who persistently denied substance abuse.
      Symptoms included ulcerating skin lesions, arthralgia and myalgia, and the
      occurrence of an ileal intussusception. The definitive diagnosis was made using
      hair testing for toxins. She recovered through cocaine abstinence, but re
      exposure resulted in a severe relapse with glomerulonephritis. Importantly, at
      time of the relapse, the patient became positive for both myeloperoxidase
      antineutrophil cytoplasmic antibody (ANCA) and proteinase 3-ANCA. Cocaine
      levamisole-induced vasculitis poses a great clinical challenge. The proper
      diagnostic strategy and therapy is still controversial. We highlight our
      diagnostic and therapeutic considerations, including hair testing for definitive
      proof of exposure. 

PMID- 26311011
TI  - Malrotation of the gut harbouring midgut volvulus in an adult with situs inversus
      totalis: a clinical delay and treatment dilemma.
AB  - A 22-year-old man experiencing infrequent episodes of abdominal pain, distension,
      non-bilious vomiting and constipation, was diagnosed with malrotation of the gut.
      He was treated conservatively over the past 10 years. He was referred to our
      hospital owing to recent aggravation of symptoms. He had no signs of peritonitis.
      On imaging, malrotation of the gut, with midgut volvolus and situs inversus
      totalis, was found. Diagnosis was confirmed during laparotomy. A large sac was
      present to the right of midline. Detorsion of the sac was performed and the sac
      was opened. The duodenum and caecum were found in the left upper abdomen adherent
      to the lateral abdominal wall. Adhesiolysis was performed and extrinsic
      compression at the duodenum relieved. The large bowel was placed on the right
      side and small bowel was placed on the left. Appendectomy and feeding jejunostomy
      were performed. Thorough analysis (clinicoradiological) is necessary before
      considering conservative management in patients known to harbour a congenital
      anomaly of the gut. 

PMID- 26311012
TI  - Cleidocranial dysostosis.

PMID- 26311013
TI  - Colonic tumour presenting as discrete upper abdominal mass.

PMID- 26311014
TI  - A light bulb moment: an unusual cause of foreign body aspiration in children.
AB  - A 15-month-old girl developed persistent cough with no associated history of
      foreign body aspiration. Chest X-ray showed a U-shaped radiopaque foreign body,
      which was initially thought to be a hairpin, in the right main bronchus. Rigid
      bronchoscopy was performed and the foreign body turned out to be a light-emitting
      diode (LED) bulb. In this article, we report our experience of LED bulb
      aspiration in children, with the view to raise the awareness of clinicians about
      this potentially life-threatening emergency. 

PMID- 26311015
TI  - Effusive-constrictive tuberculous pericarditis in the setting of penetrating
      abdominal trauma.
AB  - Tuberculous pericarditis is rare in developed nations and is most commonly
      associated with effusive-constrictive pericarditis. We present the case of a 33
      year-old man with a self-inflicted mid-abdominal stab wound. The patient
      underwent an exploratory laparotomy, revealing a grade IV pancreatic transection
      and injuries to the portal vein, right renal vein, inferior vena cava and the
      superior mesenteric vein. Repair of the vessels was performed and a
      pancreaticojejunostomy with a gastrojejunostomy was created for the pancreatic
      injury. The patient's hospital course was complicated by tuberculous effusive
      constrictive pericarditis requiring emergent median sternotomy with opening of
      the pericardial sac and eventual expiration. The final cultures from the
      pericardial fluid demonstrated tuberculosis. 

PMID- 26311016
TI  - Pulmonary tumour thrombotic microangiopathy as a cause of new-onset pulmonary
      hypertension in a patient with metastatic low-grade serous ovarian cancer.
AB  - A 78-year-old woman with metastatic low-grade serous ovarian cancer presented
      with rapidly progressive exertional dyspnoea and hypoxia, and was found to have
      new-onset severe pulmonary hypertension (PH) by right heart catheterisation. A
      diagnosis of pulmonary tumour thrombotic microangiopathy (PTTM) was made at
      autopsy. PTTM is a rare complication of advanced cancer that often presents as
      rapidly progressive PH or acute hypoxic respiratory failure. Widespread tumour
      cell emboli in the pulmonary arteries and arterioles are hypothesised to induce
      fibrocellular subintimal proliferation and microthrombi, leading to increased
      pulmonary vascular resistance and PH. PTTM arising from serous ovarian cancer is
      exceedingly rare, with only two previously reported cases. A discussion of the
      pathophysiology, diagnosis and management of PTTM is presented. 

PMID- 26311017
TI  - Efficacy and safety of once-monthly paliperidone palmitate long-acting injection
      in an elderly patient with schizophrenia.
AB  - We present detailed data on the efficacy and safety profile of paliperidone
      palmitate once-monthly long acting injectable (PP1M-LAI) in the treatment of
      schizophrenia in an elderly Caucasian woman. PP1M-LAI was initiated with starting
      doses of 150 and 100 mg on treatment days 1 and 8, respectively. Subsequent 100
      mg doses of PP1M-LAI were then administered at 4-weekly intervals. The primary
      efficacy variable was the change in Positive and Negative Syndrome Scale (PANSS)
      total score from baseline. Safety assessment variables included assessment of
      treatment emergent adverse events, clinical laboratory tests, vital sign
      measurements, ECG, Calgary Depression Scale for Schizophrenia (CDSS), mini-mental
      status examination, Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia
      Rating Scale (BARS), Simpson-Angus Scale for the Assessment of Extrapyramidal
      Side Effects (SAS) and WHO Quality of Life-BREF (WHO-QOL-BREF). The
      aforementioned variables were all monitored for changes from baseline over a
      period of 28 weeks. A reduction of PANSS total score was noted over the 28 weeks,
      demonstrating the efficacy of PP1M-LAI for the treatment of schizophrenia in our
      patient. Improvements were also noted in the BARS score, SAS score and WHO-QOL
      BREF. Negative findings were observed with regard to several pre-established
      safety variables such as blood glucose levels, prolactin levels, QTC intervals
      and weight. Overall, the addition of PP1M-LAI to the treatment regime improved
      the control of psychotic symptoms. However, iatrogenic consequences arising from
      the use of PP1M-LAI need to be considered and balanced against the primary
      efficacy of the medication.

PMID- 26311018
TI  - Genomics of crop wild relatives: expanding the gene pool for crop improvement.
AB  - Plant breeders require access to new genetic diversity to satisfy the demands of
      a growing human population for more food that can be produced in a variable or
      changing climate and to deliver the high-quality food with nutritional and health
      benefits demanded by consumers. The close relatives of domesticated plants, crop
      wild relatives (CWRs), represent a practical gene pool for use by plant breeders.
      Genomics of CWR generates data that support the use of CWR to expand the genetic
      diversity of crop plants. Advances in DNA sequencing technology are enabling the
      efficient sequencing of CWR and their increased use in crop improvement. As the
      sequencing of genomes of major crop species is completed, attention has shifted
      to analysis of the wider gene pool of major crops including CWR. A combination of
      de novo sequencing and resequencing is required to efficiently explore useful
      genetic variation in CWR. Analysis of the nuclear genome, transcriptome and
      maternal (chloroplast and mitochondrial) genome of CWR is facilitating their use
      in crop improvement. Genome analysis results in discovery of useful alleles in
      CWR and identification of regions of the genome in which diversity has been lost
      in domestication bottlenecks. Targeting of high priority CWR for sequencing will
      maximize the contribution of genome sequencing of CWR. Coordination of global
      efforts to apply genomics has the potential to accelerate access to and
      conservation of the biodiversity essential to the sustainability of agriculture
      and food production.

PMID- 26311019
TI  - Identifying preventable readmissions: an achievable goal or waiting for Godot?

PMID- 26311020
TI  - Development of the Quality Improvement Minimum Quality Criteria Set (QI-MQCS): a
      tool for critical appraisal of quality improvement intervention publications.
AB  - OBJECTIVE: Valid, reliable critical appraisal tools advance quality improvement
      (QI) intervention impacts by helping stakeholders identify higher quality
      studies. QI approaches are diverse and differ from clinical interventions. Widely
      used critical appraisal instruments do not take unique QI features into account
      and existing QI tools (eg, Standards for QI Reporting Excellence) are intended
      for publication guidance rather than critical appraisal. This study developed and
      psychometrically tested a critical appraisal instrument, the QI Minimum Quality
      Criteria Set (QI-MQCS) for assessing QI-specific features of QI publications.
      METHODS: Approaches to developing the tool and ensuring validity included a
      literature review, in-person and online survey expert panel input, and
      application to empirical examples. We investigated psychometric properties in a
      set of diverse QI publications (N=54) by analysing reliability measures and item
      endorsement rates and explored sources of disagreement between reviewers.
      RESULTS: The QI-MQCS includes 16 content domains to evaluate QI intervention
      publications: Organisational Motivation, Intervention Rationale, Intervention
      Description, Organisational Characteristics, Implementation, Study Design,
      Comparator Description, Data Sources, Timing, Adherence/Fidelity, Health
      Outcomes, Organisational Readiness, Penetration/Reach, Sustainability, Spread and
      Limitations. Median inter-rater agreement for QI-MQCS items was kappa 0.57 (83%
      agreement). Item statistics indicated sufficient ability to differentiate between
      publications (median quality criteria met 67%). Internal consistency measures
      indicated coherence without excessive conceptual overlap (absolute mean interitem
      correlation=0.19). The critical appraisal instrument is accompanied by a user
      manual detailing What to consider, Where to look and How to rate. CONCLUSIONS: We
      developed a ready-to-use, valid and reliable critical appraisal instrument
      applicable to healthcare QI intervention publications, but recognise scope for
      continuing refinement.

PMID- 26311021
TI  - H2 oxidation versus organic substrate oxidation in non-heme iron mediated
      reactions with H2O2.
AB  - Herein we show that species generated upon reaction of alpha-[Fe(CF3SO3)2(BPMCN)]
      (BPMCN = N,N'-bis(2-pyridylmethyl)-trans-1,2-diaminocyclohexane) with H2O2
      (putatively [Fe(V)(O)(OH)(BPMCN)]) is able to efficiently oxidize H2 to H2O even
      in the presence of organic substrates, while species formed in the presence of
      acetic acid (putatively [Fe(V)(O)(OAc)(BPMCN)]) prefer organic substrate
      oxidation over H2 activation. Mechanistic implications have been analysed with
      the aid of computational methods. 

PMID- 26311022
TI  - Bottom-up Fabrication of Graphene on Silicon/Silica Substrate via a Facile Soft
      hard Template Approach.
AB  - In this work, a novel soft-hard template method towards the direct fabrication of
      graphene films on silicon/silica substrate is developed via a tri-constituent
      self-assembly route. Using cetyl trimethyl ammonium bromide (CTAB) as a soft
      template, silica (SiO2) from tetramethoxysilane as a hard template, and pyrene as
      a carbon source, the self-assembly process allows the formation of a sandwich
      like SiO2/CTAB/pyrene composite, which can be further converted to high quantity
      graphene films with a thickness of ~1 nm and a size of over 5 MUm by thermal
      treatment. The morphology and thickness of the graphene films can be effectively
      controlled through the adjustment of the ratio of pyrene to CTAB. Furthermore, a
      high nonlinear refractive index n2 of ~10(-12) m(2) W(-1) is measured from
      graphene/silica hybrid film, which is six orders of magnitude larger than that of
      silicon and comparable to the graphene from chemical vapor deposition process. 

PMID- 26311024
TI  - [Stem cells in orthopaedics].
AB  - Sharing new ideas and approaches is needed to advance basic scientific research
      as well as the clinical application of stem cells. In this newsletter we present
      the current knowledge in stem cell research and therapy within the field of
      orthopaedics, presenting the definitions, types and sources of the stem cells.
      The second part of this newsletter focuses on the clinical application of stem
      cells in the therapy of tissues with very limited capacity for self-regeneration;
      this includes tendons and ligaments, particularly found in rotator cuff rupture.
      The sever problems associated with articular cartilage repair have lead to the
      need for the development of clinical research, with the aim of finding efficient
      clinical applications of stem cell therapy in cartilage defects and
      osteoarthritis. However in addition to this, such therapy could be used for the
      regeneration of bone, as in bone defect repair. The clinical outcome of stem cell
      therapy is a promising option for the treatment of cartilage, bone and tendon
      defects; however an increased sample size and additional long-term prospective
      randomised studies are needed to confirm these preliminary results. 

PMID- 26311023
TI  - Characterization of Pesticide Exposure in a Sample of Pregnant Women in Ecuador.
AB  - Few studies have detailed the prenatal pesticide exposure levels of women
      employed in or residing near large-scale agricultural industries. This study
      reports pesticide metabolite levels during and shortly after pregnancy in a pilot
      study of workers in Ecuador. Urine samples were collected for 16 rose workers and
      10 nonagricultural workers enrolled into the study in early pregnancy. We
      measured six nonspecific organophosphatedialkylphosphate (DAP) pesticide
      metabolites, two alkylenebis-dithiocarbamate pesticide metabolites [ethylene
      thiourea (ETU) and propylene thiourea (PTU)], 3,5,6-trichloro-2-pyridinol (TCPy),
      malathion dicarboxylic acid, and two pyrethroid metabolites (2,2-dimethylcyclo
      propanecarboxylic acid and 3-phenooxybenzoic acid). We collected 141 urine
      samples (mean: 5.4 per woman). We observed high detection frequencies for five
      DAP metabolites and ETU, PTU, and TCPy. We report elevated levels of ETU in the
      entire sample (median 4.24 ng/mL, IQR 2.23, 7.18), suggesting other possible non
      occupational pathways of exposure. We found no statistical differences in
      pesticide levels by current employment status, although the highest pesticide
      levels were among rose workers. We observed within-woman correlation in TCPy and
      PTU levels, but not in ETU or DAP levels. The present study is the first to
      characterize prenatal pesticide exposure levels among working women in Ecuador.
      Limitations include a small sample size and use of a convenience sample.
      Strengths include a longitudinal design and multiple urine samples per woman.
      Results provide an initial characterization of prenatal pesticide exposure levels
      and how these levels vary over pregnancy in a community impacted by agricultural
      industry and will inform further studies in the region. 

PMID- 26311025
TI  - [Histological evaluation of biomaterials administration in vivo on the cartilage,
      bone and skin healing].
AB  - Our aim was to show the benefits and limitations of histological assessment of
      healing supported by implantable biomaterials. We reviewed and showed photographs
      of the histological and immunohistochemical methods applicable for the assessment
      of desirable and undesirable effects of biomaterials on the healing of hard and
      soft tissues. Currently used methods for evaluating the microscopic effects of
      bioengineered materials on the recipient tissue are reviewed. For
      histopathological analysis, semiquantitative scoring systems can be used.
      Alternatively, the main tissue constituents may be quantified using continuous
      variables giving the numerical densities of cells, lengths of microvessels or
      connective tissue fibres, area surfaces, area and volumes fractions, or
      clustering and colocalization of microscopic objects. Using systematic uniform
      random sampling strategies at the level of tissue blocks, sections, and image
      fields leads to a reasonable low variability of the quantitative results. 

PMID- 26311026
TI  - [Spirituality and ethics in psychosomatic medicine].
AB  - A patient has to cope with an illness on a physical, mental and spiritual level.
      There exists a difference between religiousness and spirituality even though the
      approach has a common foundation. Nonreligious spirituality relates to an inner
      experience, transcendent states of consciousness, meaningfulness, responsibility,
      sympathy, ethics, humanisation, faith. We encounter the spiritual point of view
      in humanistic psychotherapy, pastoral medicine, work of hospital chaplains, New
      Age, psychotherapies with religious and alternative aspects, transpersonal
      psychotherapy, psycho-spiritual crises, unusual states of consciousness, in
      meditation, Yoga, relaxation, kinesiology, ethicotherapy, reincarnation therapy,
      positive motivation, holotropic breathing, etc. There is description of different
      degrees of spiritual development, rational and irrational feeling of
      spirituality, Quantum Physics, spiritual intelligence, neuro-theology,
      physiological change, effects on improving adaptation during stress, drugs
      addiction, etc. Spirituality in relation with ethics is discussed in terms of
      socio-biology, evolution, emotions, aggressivity, genetics and social influence.
      The work analyses the effect of stressful situations on the deterioration of
      moral attitudes: during lack of time, obedience to authority and order. It is
      described how temperament and personality disorders can affect perception of
      spirituality, guilt feeling and conscience. Stressful situations, lack of time,
      relying only on the auxiliary objective methods leads to alienation of physician
      with a patient. Spirituality can partially improve the doctor-patient
      relationship, communication and sense of responsibility. 

PMID- 26311027
TI  - [miRNA as a new marker of diabetes mellitus and pancreatic carcinoma
      progression].
AB  - Pancreatic cancer is a disease with increasing incidence and high (and nearly
      unchanged) lethality that is caused mainly due to its late diagnosis. Risk
      factors for neoplastic transformation are especially chronic pancreatitis,
      diabetes mellitus, but also obesity and smoking. The search for suitable early
      markers becomes a key element of research in this area. Such markers could be
      microRNAs, short single-stranded RNA molecules functioning as regulators of
      translation. This article serves as a review of contemporary evidence of microRNA
      in diabetes mellitus and pancreatic cancer. 

PMID- 26311028
TI  - [First experiences with preimplantation genetic screening of chromosomal
      aberrations using oligonucleotide-based array comparative genomic hybridization].
AB  - Preimplantation genetic diagnosis (PGD) is a complex approach for detecting
      genetic abnormalities in early-stage embryos using genetic or molecular
      cytogenetic methods. Recently, single cell genomic methods based on DNA
      microarrays have been used for PGD. In the presented paper, we discuss and
      demonstrate the possibility to detect copy number variation (CNVs) in
      trophectoderm cells biopsied from 5-day embryos using 60-mer oligonucleotide
      based array-CGH with CytoSure 8 * 15K Aneuploidy Array. Whereas this microarray
      platform was originally designed for analysis of unamplified DNA derived from
      many cells, the new methods, developed for single-cell genomics, allow the
      application of oligo arrays technology in preimplanation genetic diagnosis.
      Preclinical validation of single cell array-CGH was made by analysis of 30
      positive and negative controls. Validation process included whole genome
      amplification of DNA from 5-10 cells with normal karyotype and from samples with
      known aneuploidies and structural aberrations. Subsequently, we analyzed the
      whole genome profiles in 118 embryos; aneuploidies of chromosomes were observed
      in 26.7%; segmental imbalances were proved in 6.8% of embryos. Our first
      experience confirmed that this oligonucleotide-based array technique enables high
      resolution preimplantation aneuploidy screening of all the 23 chromosome pairs
      and sensitive preimplantation diagnosis of segmental imbalances such as
      deletions, duplications and amplifications. 

PMID- 26311029
TI  - [Preparedness of health system in Israel for mass emergencies].
AB  - The vast number of outbreaks of tension on the planet shows that it is impossible
      to underestimate the preparation level of population protection in emergencies.
      The possibility of a terrorist attack, including the use of particularly toxic or
      biological substances cannot be excluded or totally prevented at this point. In
      fact, there may not only be a terrorist attack. Rampant population migration
      increases the risk of the transmission of infectious diseases, even to
      considerable distances from the states where the epidemiological situation might
      not be completely under control. The current state of the Czech healthcare system
      in terms of preparedness for mass emergencies is insufficient and requires prompt
      correction, though not through hastily adopted measures. Ideally, looking into
      the success of the Israeli preparedness system, where the public has been exposed
      to high levels of threat from a variety of causes for decades, could greatly aid
      the Czech Republic in moving forward effectively. The number of victims of
      terrorist attacks there outpaces 10000, a fact that shows Israel is experienced
      in responding to emergency incidents. 

PMID- 26311030
TI  - [History of insulin production in Czechoslovakia].
AB  - The aim of the article is an effort to capture the history of insulin production
      in Czechoslovakia. Information has been obtained mainly from two Czech journals:
      "Casopis lekaru ceskych" (published since 1862) and "Prakticky lekar" (published
      since 1921). At first, imported insulin in the form of insulin injections or
      substances from which insulin was prepared appeared at the market in
      Czechoslovakia. During years 1923-1945, insulin was produced by five companies,
      since 1945 only by one company "Leciva". 

PMID- 26311031
TI  - [Professor J.Hall's merit on the development of Prague Medical Faculty].
AB  - Hall was a remarkable personality among professors in Prague Medical Faculty. He
      was an extremely capable organizer and founder of the successful institutions
      that made Prague Medical Faculty famous. In 1844 he founded the University
      Journal, in 1845 he initiated the establishment of a laboratory for chemical and
      clinical examination in the general hospital, in 1847 he opened the University
      outpatient clinic, the first in the Austrian monarchy. He was an excellent
      teacher; however, his publications activity was small. Professor Hall belongs to
      the principal representatives of the so-called Prague Medical School. 

PMID- 26311032
TI  - [Cutaneous polyarteritis nodosa: A rare cause of chronic ulcers].
AB  - Cutaneous polyarteritis nodosa, a special form of polyarteritis nodosa (PAN)
      without systemic involvement, is classified as one of the ANCA-negative
      vasculitides of small and medium-sized vessels. It is a very rare disease with
      unknown etiology and occurs more commonly in women over the age of 40. Typical
      skin lesions are subcutaneous nodules, livedo racemosa, and ulcerations. We
      report the case of a 46-year-old woman presenting to our outpatient department
      who reported having very painful ulcerations of the lower legs with unknown
      origin for 6 months.

PMID- 26311033
TI  - [Clotrimazol in combination with other active ingredients].

PMID- 26311034
TI  - In Utero Exposure to a Cardiac Teratogen Causes Reversible Deficits in Postnatal
      Cardiovascular Function, But Altered Adaptation to the Burden of Pregnancy.
AB  - Congenital heart defects (CHD) are the most common birth anomaly and while many
      resolve spontaneously by 1 year of age, the lifelong burden on survivors is
      poorly understood. Using a rat model of chemically induced CHD that resolve
      postnatally, we sought to characterize the postnatal changes in cardiac function,
      and to investigate whether resolved CHD affects the ability to adapt to the
      increased the cardiovascular (CV) burden of pregnancy. To generate rats with
      resolved CHD, pregnant rats were administered distilled water or dimethadione
      (DMO) [300 mg/kg b.i.d. on gestation day (gd) 9 and 10] and pups delivered
      naturally. To characterize structural and functional changes in the heart,
      treated and control offspring were scanned by echocardiography on postnatal day
      4, 21, and 10-12 weeks. Radiotelemeters were implanted for continuous monitoring
      of hemodynamics. Females were mated and scanned by echocardiography on gd12 and
      gd18 during pregnancy. On gd18, maternal hearts were collected for structural and
      molecular assessment. Postnatal echocardiography revealed numerous structural and
      functional differences in treated offspring compared with control; however, these
      resolved by 10-12 weeks of age. The CV demand of pregnancy revealed differences
      between treated and control offspring with respect to mean arterial pressure, CV
      function, cardiac strain, and left ventricular gene expression. In utero exposure
      to DMO also affected the subsequent generation. Gd18 fetal and placental weights
      were increased in treated F2 offspring. This study demonstrates that in utero
      chemical exposure may permanently alter the capacity of the postnatal heart to
      adapt to pregnancy and this may have transgenerational effects.

PMID- 26311036
TI  - Radial alignment of c-channel nanorods in 3D porous TiO2 for eliciting enhanced
      Li storage performance.
AB  - A c-channel formed inside stacked (001) planes in rutile TiO2 exhibits the lowest
      energy barrier for Li migration. Based on this rationale, we proposed a three
      dimensional TiO2 sphere comprised of radially assembled c-channel specialized
      nanorods in order to maximize Li storage. 

PMID- 26311035
TI  - Molecular composition and ultrastructure of Jurassic paravian feathers.
AB  - Feathers are amongst the most complex epidermal structures known, and they have a
      well-documented evolutionary trajectory across non-avian dinosaurs and basal
      birds. Moreover, melanosome-like microbodies preserved in association with fossil
      plumage have been used to reconstruct original colour, behaviour and physiology.
      However, these putative ancient melanosomes might alternatively represent
      microorganismal residues, a conflicting interpretation compounded by a lack of
      unambiguous chemical data. We therefore used sensitive molecular imaging,
      supported by multiple independent analytical tests, to demonstrate that the
      filamentous epidermal appendages in a new specimen of the Jurassic paravian
      Anchiornis comprise remnant eumelanosomes and fibril-like microstructures,
      preserved as endogenous eumelanin and authigenic calcium phosphate. These results
      provide novel insights into the early evolution of feathers at the sub-cellular
      level, and unequivocally determine that melanosomes can be preserved in fossil
      feathers. 

PMID- 26311037
TI  - Surface plasmon resonance based on molecularly imprinted nanoparticles for the
      picomolar detection of the iron regulating hormone Hepcidin-25.
AB  - BACKGROUND: Molecularly imprinted polymer (MIP) technique is a powerful mean to
      produce tailor made synthetic recognition sites. Here precipitation
      polymerization was exploited to produce a library of MIP nanoparticles (NPs)
      targeting the N terminus of the hormone Hepcidin-25, whose serum levels correlate
      with iron dis-metabolisms and doping. Biotinylated MIP NPs were immobilized to
      NeutrAvidinTM SPR sensor chip. The response of the MIP NP sensor to Hepcidin-25
      was studied. FINDINGS: Morphological analysis showed MIP NPs of 20-50 nm; MIP NP
      exhibited high affinity and selectivity for the target analyte: low nanomolar Kds
      for the interaction NP/Hepcidin-25, but none for the NP/non regulative Hepcidin
      20. The MIP NP were integrated as recognition element in SPR allowing the
      detection of Hepcidin-25 in 3 min. Linearity was observed with the logarithm of
      Hepcidin-25 concentration in the range 7.2-720 pM. LOD was 5 pM. The response for
      Hepcidin-20 was limited. Hepcidin-25 determination in real serum samples spiked
      with known analyte concentrations was also attempted. CONCLUSION: The integration
      of MIP NP to SPR allowed the determination of Hepcidin-25 at picomolar
      concentrations in short times outperforming the actual state of art. Optimization
      is still needed for real sample measurements in view of future clinical
      applications.

PMID- 26311038
TI  - Factors associated with seizure occurrence and long-term seizure control in
      pediatric brain arteriovenous malformation: a retrospective analysis of 89
      patients.
AB  - BACKGROUND: Few studies have examined seizures in pediatric brain arteriovenous
      malformation. In our study, risk factors associated with seizure occurrence and
      long-term seizure control outcomes after different treatments in pediatric
      arteriovenous malformation patients were investigated. METHODS: A retrospective
      analysis was conducted with clinical data from a cohort of 89 pediatric brain
      arteriovenous malformation patients acquired between 2008 and 2013. Univariate
      and multivariate analyses were used to assess risk factors associated with
      seizure incidence. Patients who presented with seizure before treatment were
      evaluated using the Engel classification during the follow-up period. RESULTS: A
      higher risk of seizure occurrence was observed in large size and unruptured brain
      arteriovenous malformations using multivariate logistic regression analysis (p <
      0.05). A total of 22 children, who presented with seizure before the
      interventions, were included in subsequent analysis. During a mean follow-up
      period of 2.3 years after the intervention, 12 (55 %) of these children were
      classified as Engel class I after treatment. CONCLUSIONS: Seizures were the most
      common symptom in unruptured bAVMs. Size of the brain arteriovenous malformation
      is highly significant to seizure occurrence. Patients with cerebral hemorrhage
      are prone to having an acute seizure occurrence. The different therapies examined
      all improved seizure control to varying degrees.

PMID- 26311039
TI  - An N-terminal antibody promotes the transformation of amyloid fibrils into
      oligomers and enhances the neurotoxicity of amyloid-beta: the dust-raising
      effect.
AB  - BACKGROUND: Senile plaques consisting of amyloid-beta (Abeta) are the major
      pathological hallmark of Alzheimer's disease (AD) and have been the primary
      therapeutic target. Immunotherapies, which are designed to remove brain Abeta
      deposits, increased levels of soluble Abeta and accelerated brain atrophy in some
      clinical trials, suggesting that the solubilization of Abeta deposition might
      facilitate the formation of more toxic Abeta oligomers and enhance neurotoxicity.
      METHODS: The capacity of antibodies against different epitopes of Abeta to
      disaggregate preformed Abeta fibrils was investigated. The co-incubation of
      antibodies and Abeta fibrils was then tested for neurotoxicity both in vitro and
      in vivo. RESULTS: After the incubation of preformed Abeta fibrils with the N
      terminal antibody 6E10, the fibrils were decreased, while the oligomers, mostly
      dimers and trimers, were significantly increased. However, no such effects were
      observed for antibodies targeting the middle domain (4G8) and C-terminus of Abeta
      (8G7). The co-incubates of preformed Abeta fibrils with 6E10 were more
      neurotoxic, both in vitro and in vivo, than the co-incubates with 4G8 and 8G7.
      CONCLUSIONS: Our results indicate that the antibody targeting the N-terminus of
      Abeta promoted the transformation of Abeta from fibrils into oligomers and
      increased neurotoxicity. Immunotherapies should take into consideration the
      enhanced neurotoxicity associated with the solubilization of Abeta deposits by
      antibodies against the Nterminus of Abeta.

PMID- 26311040
TI  - Hepatotropic viruses as etiological agents of acute liver failure and related
      outcomes among children in India: a retrospective hospital-based study.
AB  - BACKGROUND: Acute liver failure (ALF) is marked by a sudden loss of hepatic
      function and is associated with a high mortality rate in children. The etiology
      of ALF is shown to vary geographically. This study assessed the frequency of
      hepatotropic viruses as etiological agents of ALF in Indian children. METHODS:
      This retrospective study enrolled children aged 0-18 years with confirmed ALF
      admitted to Christian Medical College, Vellore and King Edward Memorial Hospital
      and Research Center, Pune between January 2003 and December 2005. The frequency
      of hepatotropic viruses as etiological agents in children with ALF aged <=18
      years was calculated with 95% confidence interval (CI). Descriptive analyses of
      demographic characteristics, clinical signs and symptoms of ALF, choice of
      treatment and outcomes were performed. RESULTS: Of 76 children enrolled, 54 were
      included in the per-protocol analyses. Mean age of children with ALF was 5.43
      years (standard deviation = 3.62); 51.9% (28/54) were female. The percentage of
      children positive for anti-hepatitis A virus (HAV) IgM and hepatitis B surface
      antigen was 65.9% (27/41; 95% CI 49.4-79.9) and 15.9% (7/44; 95% CI 6.6-30.1),
      respectively. The final cause of ALF was HAV (36.3%) followed by hepatitis B
      virus (HBV; 8.8%). Before and during admission, encephalopathy was observed in
      77.8% (42/54) and 63.0% (34/54) of children, respectively. A high number of
      children (46/54; 85.2%) required intensive care and ALF was fatal in 24.1%
      (13/54). The proportion of deaths due to HAV and HBV was 18.5% (5/27) and 57.1%
      (4/7), respectively. CONCLUSIONS: HAV and HBV were the most common etiological
      agents of ALF in Indian children. Primary prevention by vaccination against HAV
      and HBV in young children may be useful in the prevention of ALF due to viral
      hepatitis in India.

PMID- 26311041
TI  - Enhancement of the anti-inflammatory activity of temporin-1Tl-derived
      antimicrobial peptides by tryptophan, arginine and lysine substitutions.
AB  - Temporin-1Tl (TL) is a 13-residue frog antimicrobial peptide (AMP) exhibiting
      potent antimicrobial and anti-inflammatory activity. To develop novel AMP with
      improved anti-inflammatory activity and antimicrobial selectivity, we designed
      and synthesized a series of TL analogs by substituting Trp, Arg and Lys at
      selected positions. Except for Escherichia coli and Staphylococcus epidermidis,
      all TL analogs exhibited retained or increased antimicrobial activity against
      seven bacterial strains including three methicillin-resistant Staphylococcus
      aureus strains compared with TL. TL-1 and TL-4 showed a little increase in
      antimicrobial selectivity, while TL-2 and TL-3 displayed slightly decreased
      antimicrobial selectivity because of their about twofold increased hemolytic
      activity. All TL analogs demonstrated greatly increased anti-inflammatory
      activity, evident by their higher inhibition of the production tumor necrosis
      factor-alpha (TNF-alpha) and nitric oxide and the mRNA expression of inducible
      nitric oxide synthase and TNF-alpha in lipopolysaccharide (LPS)-stimulated
      RAW264.7 macrophage cells, compared with TL. Taken together, the peptide anti
      inflammatory activity is as follows: TL-2 ~ TL-3 ~ TL-4 > TL-1 > TL. In addition,
      LPS binding ability of the peptides corresponded with their anti-inflammatory
      activity. These results apparently suggest that the anti-inflammatory activity of
      TL analogs is associated with the direct binding ability between these peptides
      and LPS. Collectively, our designed TL analogs possess improved anti-inflammatory
      activity and retain antimicrobial activity without a significant increase in
      hemolysis. Therefore, it is evident that our TL analogs constitute promising
      candidates for the development of peptide therapeutics for gram-negative
      bacterial infection.

PMID- 26311042
TI  - A comprehensive repertoire of prokaryotic species identified in human beings.
AB  - The compilation of the complete prokaryotic repertoire associated with human
      beings as commensals or pathogens is a major goal for the scientific and medical
      community. The use of bacterial culture techniques remains a crucial step to
      describe new prokaryotic species. The large number of officially acknowledged
      bacterial species described since 1980 and the recent increase in the number of
      recognised pathogenic species have highlighted the absence of an exhaustive
      compilation of species isolated in human beings. By means of a thorough
      investigation of several large culture databases and a search of the scientific
      literature, we built an online database containing all human-associated
      prokaryotic species described, whether or not they had been validated and have
      standing in nomenclature. We list 2172 species that have been isolated in human
      beings. They were classified in 12 different phyla, mostly in the Proteobacteria,
      Firmicutes, Actinobacteria, and Bacteroidetes phyla. Our online database is
      useful for both clinicians and microbiologists and forms part of the Human
      Microbiome Project, which aims to characterise the whole human microbiota and
      help improve our understanding of the human predisposition and susceptibility to
      infectious agents. 

PMID- 26311043
TI  - Impact of board-certificated physiatrists on rehabilitation outcomes in elderly
      patients after hip fracture: An observational study using the Japan
      Rehabilitation Database.
AB  - AIM: To clarify the impact on rehabilitation outcomes of board-certificated
      physiatrists (BCP) as the physicians with primary responsibility for elderly
      patients in convalescent rehabilitation wards after hip fracture. METHODS: The
      present retrospective observational study used 2005-2013 data from the Japan
      Rehabilitation Database. We identified in-hospital patients with hip fracture
      admitted to rehabilitation wards. After applying exclusion criteria, 824 patients
      were eligible. The primary outcome was functional independence measure instrument
      efficiency. RESULTS: BCP were responsible for the care of 46% of patients with
      hip fracture. Patients who were managed by a BCP had significantly higher mean
      functional independence measure efficiency than patients who were not, both
      before and after adjustment by inverse propensity-score weighting (0.37 vs 0.26;
      P = 0.04 and 0.39 vs 0.26; P < 0.01, respectively). Additionally, the mean length
      of stay was significantly shorter in patients who were managed by BCP than in
      those who were not, both before and after inverse propensity-score weighting (65
      vs 71 days, P = 0.04 and 64 vs 69 days, P < 0.01, respectively). CONCLUSIONS: Our
      data suggest that the participation of BCP is associated with good rehabilitation
      outcomes in patients with hip fracture at convalescent rehabilitation wards.
      Geriatr Gerontol Int 2016; 16: 963-968.

PMID- 26311044
TI  - Abstracts from Muscle Study Group Meeting: Experimental Therapeutics Across the
      Spectrum of Neuromuscular Disease Snowbird Ski & Summer Resort Snowbird, UT,
      September 19-21, 2015.

PMID- 26311045
TI  - Human placental extract exerts hair growth-promoting effects through the GSK
      3beta signaling pathway in human dermal papilla cells.
AB  - Human placental extract (HPE) is widely used in Korea to relieve fatigue.
      However, its effects on human dermal papilla cells (hDPCs) remain unknown. In the
      present study, in an effort to develop novel therapies to promote hair growth, we
      screened HPE. We demonstrate that HPE has hair growth-promoting activities and
      induces beta-catenin expression through the inhibition of glycogen synthase
      kinase-3beta (GSK-3beta) by phosphorylation in hDPCs. Treatment with HPE
      significantly increased the viability of the hDPCs in a concentration-dependent
      manner, as shown by bromodeoxyuridine (BrdU) assay. HPE also significantly
      increased the alkaline phosphatase (ALP) expression levels. The increased beta
      catenin levels and the inhibition of GSK-3beta (Ser9) by phosphorylation
      suggested that HPE promoted the hair-inductive capacity of hDPCs. We compared the
      effects of treatment with HPE alone and treatment with HPE in conjunction with
      minoxidil (MXD). We found that HPE plus MXD effectively inhibited GSK-3beta by
      phosphorylation (Ser9) in the hDPCs. Moreover, we demonstrated that HPE was
      effective in inducing root hair elongation in rat vibrissa hair follicles, and
      that treatment with HPE led to a delay in catagen progression. Overall, our
      findings suggest that HPE promotes hair growth and may thus provide the basis of
      a novel therapeutic strategy for the clinical treatment of hair loss. 

PMID- 26311046
TI  - A role for the dehydrogenase DHRS7 (SDR34C1) in prostate cancer.
AB  - Several microarray studies of prostate cancer (PCa) samples have suggested
      altered expression of the "orphan" enzyme short-chain dehydrogenase/reductase
      DHRS7 (retSDR4, SDR34C1). However, the role of DHRS7 in PCa is largely unknown
      and the impact of DHRS7 modulation on cancer cell properties has not yet been
      studied. Here, we investigated DHRS7 expression in normal human prostate and PCa
      tissue samples at different tumor grade using tissue microarray and
      immunovisualization. Moreover, we characterized the effects of siRNA-mediated
      DHRS7 knockdown on the properties of three distinct human prostate cell lines. We
      found that DHRS7 protein expression decreases alongside tumor grade, as judged by
      the Gleason level, in PCa tissue samples. The siRNA-mediated knockdown of DHRS7
      expression in the human PCa cell lines LNCaP, BPH1, and PC3 significantly
      increased cell proliferation in LNCaP cells as well as cell migration in all of
      the investigated cell lines. Furthermore, cell adhesion was decreased upon DHRS7
      knockdown in all three cell lines. To begin to understand the mechanisms
      underlying the effects of DHRS7 depletion, we performed a microarray study with
      samples from LNCaP cells treated with DHRS7-specific siRNA. Several genes
      involved in cell proliferation and adhesion pathways were found to be altered in
      DHRS7-depleted LNCaP cells. Additionally, genes of the BRCA1/2 pathway and the
      epithelial to mesenchymal transition regulator E-cadherin were altered following
      DHRS7 knockdown. Based on these results, further research is needed to evaluate
      the potential role of DHRS7 as a tumor suppressor and whether its loss-of
      function promotes PCa progression and metastasis. 

PMID- 26311047
TI  - Harlequin Skin Changes Caused by Extreme Rectal Pain.

PMID- 26311048
TI  - A Rare Cause of Periodic Vomiting With Hematemesis in a 36-Year-Old Man.

PMID- 26311049
TI  - The upregulated alpha-catulin expression was involved in head-neck squamous cell
      carcinogenesis by promoting proliferation, migration, invasion, and epithelial to
      mesenchymal transition.
AB  - Rho signaling component, alpha-catulin, is a cytoskeletal linker protein and
      plays an important role in apoptotic and senescence resistance, cytoskeletal
      reorganization, mobility, invasion, and epithelial to mesenchymal transition
      (EMT) of cancer cells. Here, we transfected alpha-catulin-expressing plasmid into
      head and neck squamous cell carcinoma (HNSCC) cell and examined the phenotypes
      and relevant molecules. alpha-catulin expression was detected on tissue
      microarray containing squamous epithelium, dysplasia, and cancer of head and neck
      by immunohistochemistry. It was found that alpha-catulin overexpression resulted
      in faster growth, migration and invasion, lower apoptosis, G2/M progression, and
      EMT than the mock and control (P < 0.05). alpha-catulin overexpression increased
      the expression of Cyclin E1, cdc2, survivin, Bcl-2, MMP-2, MMP-9, and N-cadherin
      but decreased the expression of Caspase-3 and E-cadherin by real-time PCR (P <
      0.05). alpha-catulin expression was stronger in primary cancers than those in
      normal squamous epithelium and dysplasia (P < 0.05), but not correlated with
      aggressive behaviors or adverse prognosis of HNSCC patients (P > 0.05).
      Multivariate survival analysis showed that distant metastasis and TNM staging
      were independent prognostic factors for overall survival of the HNSCC patients (P
      < 0.05). These data indicated that upregulated expression of alpha-catulin
      protein might have impact on the tumorigenesis of HNSCC possibly by reducing
      apoptosis, enhancing proliferation, cell cycle progression, migration, invasion,
      and EMT. It might be regarded as a potential marker for head and neck
      carcinogenesis or a target of gene therapy for HNSCCs. 

PMID- 26311050
TI  - PEBP4 promoted the growth and migration of cancer cells in pancreatic ductal
      adenocarcinoma.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most common malignancies in
      the world. Numerous studies have linked the activation of AKT to the progression
      of PDAC. Phosphatidylethanolamine-binding protein 4 (PEBP4) has been reported to
      be upregulated in various cancer types. However, its expression pattern and
      biological functions in PDAC are unknown. In this study, it was found that the
      messenger RNA (mRNA) and protein level of PEBP4 was elevated in PDAC samples.
      Forced expression of PEBP4 in PDAC cell lines promoted cell growth and migration,
      while downregulation of PEBP4 in PDAC cells by RNA interference (RNAi) inhibited
      the growth, migration, and metastasis of the cancer cells. PEBP4 interacted with
      AKT and promoted the phosphorylation of serine 473 in AKT. Collectively, this
      study suggested that PEBP4 might promote the progression of PDAC through
      activating AKT signaling and PEBP4 might be a promising therapeutic target for
      PDAC treatment. 

PMID- 26311051
TI  - Association of the functional BCL-2 rs2279115 genetic variant and small cell lung
      cancer.
AB  - As a well-known oncogene, B cell lymphoma-2 (BCL-2) can promote cancer cell
      survival through preventing their apoptosis. Several functional BCL-2 single
      nucleotide polymorphisms (SNPs), such as rs2279115, rs1801018, and rs1564483,
      have been identified and might contribute to cancer susceptibility. However, the
      involvement of these SNPs in small cell lung cancer (SCLC) was still unclear. As
      a result, we investigated associations between these three genetic variants and
      SCLC risk in a case-control design. Genotypes were determined in two independent
      case-control sets consisted of 520 SCLC patients and 1040 controls from two
      medical centers. Odds ratios (ORs) and 95 % confidence intervals (CIs) were
      calculated utilizing unconditional logistic regression. We found that only BCL-2
      rs2279115 genetic variant significantly contributed to decreased SCLC risk in
      Chinese Han populations, with the rs2279115 A allele as the protective allele.
      Stratified analyses of association between BCL2 rs2279115 SNP and SCLC risk
      indicated that the functional polymorphism was only significantly associated with
      decreased risk of the limited stage SCLC but not the extensive stage disease. Our
      results indicate that the BCL-2 rs2279115 genetic variant was associated with
      SCLC risk in Chinese populations and support the hypothesis that SNPs in
      regulatory regions of oncogenes might contribute to cancer susceptibility. 

PMID- 26311052
TI  - Long non-coding RNA MALAT1 modulates radiosensitivity of HR-HPV+ cervical cancer
      via sponging miR-145.
AB  - Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a lncRNA
      playing oncogenic role in several cancers, including cervical cancer. However,
      its role in radiosensitivity of cervical cancer is not yet well understood. This
      study explored the role of MALAT1 in radiosensitivity of high-risk human
      papillomavirus (HR-HPV)-positive cervical cancer and whether there is a ceRNA
      mechanism which participated in its regulation over radiosensitivity. Based on
      tissue samples from 50 cervical cancer cases and 25 healthy controls, we found
      MALAT1 expression was significantly higher in radioresistant than in
      radiosensitive cancer cases. In addition, MALAT1 and miR-145 expression inversely
      changed in response to irradiation in HR-HPV+ cervical cancer cells. By using
      clonogenic assay and flow cytometry analysis of cell cycle distribution and
      apoptosis, we found CaSki and Hela cells with knockdown of MALAT1 had
      significantly lower colony formation, higher ratio of G2/M phase block and higher
      ratio of cell apoptosis. By performing RNA-binding protein immunoprecipitation
      (RIP) assay and RNA pull-down assay, we confirmed that miR-145 and MALAT1 were in
      the same Ago2 complex and there was a reciprocal repression between them. Then,
      we explored the function of MALAT1-miR-145 in radiosensitivity of cervical
      cancers cells and demonstrated that si-MALAT1 and miR-145 had some level of
      synergic effect in reducing cancer cell colony formation, cell cycle regulation,
      and inducing apoptosis. These findings provide an important clue about microRNA
      lncRNA interaction in the mechanism of radioresistance of cervical cancer. 

PMID- 26311053
TI  - Spiritual Coping: A Gateway to Enhancing Family Communication During Cancer
      Treatment.
AB  - The researchers examined the spiritual coping, family communication, and family
      functioning of 95 participants in 34 families by an online survey. Multilevel
      linear regression was used to test whether individuals' and families' higher
      endorsement of more use of spiritual coping strategies to deal with a member's
      cancer would be associated with higher scores on family communication and family
      functioning, and whether better communication would also be associated with
      higher family functioning scores. Results revealed that spiritual coping was
      positively associated with family communication, and family communication was
      positively associated with healthier family functioning. The researchers provide
      suggestions for further research. 

PMID- 26311054
TI  - The Tzu Chi Silent Mentor Program: Application of Buddhist Ethics to Teach
      Student Physicians Empathy, Compassion, and Self-Sacrifice.
AB  - The Buddhist Tzu Chi Silent Mentor Program promotes the donation of one's body to
      science as a selfless act by appealing to the Buddhist ethics of compassion and
      self-sacrifice. Together, faculty, families, and donors help medical students to
      learn the technical, spiritual, emotional, and psychological aspects of medicine.
      Students assigned to each "Silent Mentor" visit the family to learn about the
      donor's life. They see photos and hear family members' stories. Afterwards,
      students write a brief biography of the donor which is posted on the program
      website, in the medical school, and on the dissection table. In this paper, we:
      (1) summarize the Silent Mentor Program; (2) describe findings from an assessment
      of medical students who recently completed a new version of the program in
      Malaysia; and (3) explore how healthcare settings could benefit from this
      innovative program. 

PMID- 26311055
TI  - Patient assessment within the context of healthcare delivery packages: A
      comparative analysis.
AB  - BACKGROUND: Due to an increased focus on productivity and cost-effectiveness,
      many countries across the world have implemented a variety of tools for
      standardizing diagnostics and treatment. In Denmark, healthcare delivery packages
      are increasingly used for assessment of patients. A package is a tool for
      creating coordination, continuity and efficient pathways; each step is pre
      booked, and the package has a well-defined content within a predefined category
      of diseases. The aim of this study was to investigate how assessment processes
      took place within the context of healthcare delivery packages. METHODS: The study
      used a constructivist Grounded Theory approach. Ethnographic fieldwork was
      carried out in three specialized units: a mental health unit and two multiple
      sclerosis clinics in Southern Denmark, which all used assessment packages.
      Several types of data were sampled through theoretical sampling. Participant
      observation was conducted for a total of 126h. Formal and informal interviews
      were conducted with 12 healthcare professionals and 13 patients. Furthermore,
      audio recordings were made of 9 final consultations between physicians and
      patients; 193min of recorded consultations all in all. Lastly, the medical
      records of 13 patients and written information about packages were collected. The
      comparative, abductive analysis focused on the process of assessment and the work
      made by all the actors involved. In this paper, we emphasized the work of
      healthcare professionals. RESULTS: We constructed five interrelated categories:
      1. "Standardized assessing", 2. "Flexibility", which has two sub-categories, 2.1.
      "Diagnostic options" and 2.2. "Time and organization", and, finally, 3.
      "Resisting the frames". The process of assessment required all participants to
      perform the predefined work in the specified way at the specified time.
      Multidisciplinary teamwork was essential for the success of the process. The
      local organization of the packages influenced the assessment process, most
      notably the pre-defined scope of relevant diseases targeted by the package. The
      inflexible frames of the assessment package could cause resistance among
      clinicians. Moreover, expert knowledge was an important factor for the efficiency
      of the process. Some types of organizational work processes resulted in many
      patients being assessed, but without being diagnosed with at package-relevant
      disease. CONCLUSION: Limiting the grounds for using specialist knowledge in
      structured health care delivery may affect specialists' sense of professional
      autonomy and can result in professionals employing strategies to resist the
      frames of the packages. Finally, when organizing healthcare delivery packages, it
      seems important to consider how to make the optimal use of specialist knowledge.

PMID- 26311056
TI  - Citrate pharmacokinetics at high levels of circuit citratemia during coupled
      plasma filtration adsorption.
AB  - BACKGROUND: The heparin requirement for coupled plasma filtration adsorption
      (CPFA) is usually high. Heparin administration often cannot be adherent to
      prescription, leading to a premature clotting of circuit and an insufficient
      volume of treated plasma. Regional citrate anticoagulation (RCA) could be an
      attractive alternative; however, no data are available on citrate
      pharmacokinetics at high levels of circuit citratemia. METHODS: Fifteen septic
      shock patients with acute kidney injury undergoing CPFA with RCA at target
      circuit citratemia of 6 mmol/L were treated with CPFA-haemofiltration in pure
      predilution (CPFA-HF predilution group, n = 5 patients), or predilution
      haemodiafiltration (CPFA-HDF predilution group, n = 5 patients) or pre- and
      postdilution haemofiltration (CPFA-HF pre/postdilution group, n = 5 patients).
      Citrate pharmacokinetics was carried out through its determination in systemic
      and circuit blood, and effluent at time 0, 0.2, 1, 3, 6 and 9 h. RESULTS: The
      systemic concentrations of citrate in the CPFA-HF predilution group significantly
      increased over the sessions (from basal level of 0.21 to 0.76 mmol/L at 3 h),
      whereas they did not change in CPFA-HDF predilution and CPFA-HF pre/postdilution
      groups. Circuit plasma citrate concentrations (from 3 to 8 mmol/L) correlated
      strongly with circuit iCa++ levels (Spearman R = -0.7022, P < 0.01). Sieving
      coefficients of citrate were near the unit in all three groups and unrelated to
      blood and infusion flow rates in predilution. However, the amount of citrate
      removed by effluent was ~40% for the CPFA-HF predilution group and reached 60%
      for both the CPFA-HDF predilution and CPFA-HF pre/postdilution groups (P < 0.05).
      As for the efficiency of plasmafiltration, the plasmafiltrate volume (from 17 to
      20 mL/kg/day) was not significantly different among the groups. CONCLUSIONS:
      These results demonstrated that in refractory septic shock patients on CPFA at
      circuit citratemia of 6 mmol/L both HDF predilution and HF pre/postdilution were
      the best dialysis modalities to maintain a normal systemic citratemia through a
      high rate of citrate loss in the effluent.

PMID- 26311057
TI  - Urine biomarkers of kidney injury among adolescents in Nicaragua, a region
      affected by an epidemic of chronic kidney disease of unknown aetiology.
AB  - BACKGROUND: An epidemic of chronic kidney disease (CKD) of non-traditional
      aetiology has been recently recognized by health authorities as a public health
      priority in Central America. Previous studies have identified strenuous manual
      work, agricultural activities and residence at low altitude as potential risk
      factors; however, the aetiology remains unknown. Because individuals are
      frequently diagnosed with CKD in early adulthood, we measured biomarkers of
      kidney injury among adolescents in different regions of Nicaragua to assess
      whether kidney damage might be initiated during childhood. METHODS: Participants
      include 200 adolescents aged 12-18 years with no prior work history from four
      different schools in Nicaragua. The location of the school served as a proxy for
      environmental exposures and geographic locations were selected to represent a
      range of factors that have been associated with CKD in adults (e.g. altitude,
      primary industry and CKD mortality rates). Questionnaires, urine dipsticks and
      kidney injury biomarkers [interleukin-18, N-acetyl-d-glucosaminidase (NAG),
      neutrophil gelatinase-associated lipocalin (NGAL) and albumin-creatinine ratio]
      were assessed. Biomarker concentrations were compared by school using linear
      regression models. RESULTS: Protein (3.5%) and glucose (1%) in urine measured by
      dipstick were rare and did not differ by school. Urine biomarkers of tubular
      kidney damage, particularly NGAL and NAG, showed higher concentrations in those
      schools and regions within Nicaragua that were defined a priori as having
      increased CKD risk. Painful urination was a frequent self-reported symptom.
      CONCLUSIONS: Although interpretation of these urine biomarkers is limited because
      of the lack of population reference values, results suggest the possibility of
      early kidney damage prior to occupational exposures in these adolescents.

PMID- 26311058
TI  - Sodium restriction potentiates the renoprotective effects of combined vitamin D
      receptor activation and angiotensin-converting enzyme inhibition in established
      proteinuric nephropathy.
AB  - Background: Renin-angiotensin-aldosterone system (RAAS) blockade provides
      renoprotective effects in chronic kidney disease (CKD); yet progressive renal
      function loss remains common. Dietary sodium restriction potentiates the
      renoprotective effects of RAAS blockade. Vitamin D receptor activator (VDRA)
      treatment reduces proteinuria, inflammation and fibrosis, but whether these
      effects depend on sodium intake has not been studied. We hypothesized that the
      renoprotective effects of VDRA treatment, with or without RAAS blockade, are
      modulated by sodium intake. Methods: Six weeks after the induction of adriamycin
      nephrosis in Wistar rats, i.e. with established proteinuria, animals were treated
      with the VDRA paricalcitol, lisinopril, the combination, or vehicle; each
      treatment was given during either a high- (2% NaCl) or a low-sodium (0.05% NaCl)
      diet for 6 weeks. We assessed proteinuria, blood pressure, renal macrophage
      accumulation and renal expression of the pre-fibrotic marker alpha-smooth muscle
      actin (alpha-SMA) at the end of the treatment. Results: Both paricalcitol and
      lisinopril individually, as well as in combination, reduced proteinuria and
      glomerular and interstitial inflammation during a low-sodium diet, but not during
      a high-sodium diet. All interventions also reduced focal glomerulosclerosis and
      interstitial expression of alpha-SMA during the low-sodium diet, while similar
      trends were observed during the high-sodium diet. The renoprotective effects of
      paricalcitol were not accompanied by blood pressure reduction. As proteinuria was
      already abolished by lisinopril during the low-sodium diet, the addition of
      paricalcitol had no further effect on proteinuria or downstream inflammatory or
      pre-fibrotic changes. Conclusion: The renoprotective effects of the VDRA
      paricalcitol are blood pressure independent but do depend on dietary sodium
      status. The combination of RAAS blockade, dietary sodium restriction and VDRA may
      be a promising intervention to further retard renal function loss in CKD.

PMID- 26311059
TI  - Development and Implementation of Autoverification Rules for ELISA Results of HBV
      Serological Markers.
AB  - Autoverification is a process of using computer-based rules to verify clinical
      laboratory test results without manual review. But to date, there are few
      published articles on the use of autoverification over the course of years in a
      clinical laboratory. In our study, we firstly described the development and
      implementation of autoverification rules for enzyme-linked immunosorbent assay
      (ELISA) results of hepatitis B virus (HBV) serological markers in a clinical
      immunology laboratory. We designed the autoverification rules for HBV by using
      Boolean logic on five clinically used serological markers in accordance with the
      framework of AUTO-10A, issued by the American Clinical Laboratory Standards
      Institute in 2006. The rules were written into the laboratory information system
      (LIS) and installed in the computer, so we could use the LIS to screen the test
      results. If the results passed the autoverification rules, they could be sent to
      doctors immediately. To evaluate the autoverification rules, we applied the real
      time data of 11,585 patients with the autoverification rules. The
      autoverification rate of the five HBV serological markers was 79.5%. Furthermore,
      the turnaround time (TAT) was reduced by 38% (78 minutes vs. 126 minutes). The
      error rate was nearly eliminated. These results show that using LIS with
      autoverification rules can shorten TAT, enhance efficiency, and reduce manual
      review errors. 

PMID- 26311060
TI  - Mammalian Genotyping Using Acoustic Droplet Ejection for Enhanced Data
      Reproducibility, Superior Throughput, and Minimized Cross-Contamination.
AB  - Genetically engineered animal models are major tools of a drug discovery pipeline
      because they facilitate understanding of the molecular and biochemical basis of
      disease. These highly complex models of human disease often require increasingly
      convoluted genetic analysis. With growing needs for throughput and consistency,
      we find that traditional aspiration-and-dispense liquid-handling robots no longer
      have the required speed, quality, or reproducibility.We present an adaptation and
      installation of an acoustic droplet ejection (ADE) liquid-handling system for
      ultra-high-throughput screening of genetically engineered models. An ADE system
      is fully integrated with existing laboratory processes and platforms to
      facilitate execution of PCR and quantitative PCR (qPCR) reactions. Such a
      configuration permits interrogation of highly complex genetic models in a variety
      of backgrounds. Our findings demonstrate that a single ADE system replaces 8-10
      traditional liquid-handling robots while increasing quality and
      reproducibility.We demonstrate significant improvements achieved by transitioning
      to an ADE device: extremely low detectable cross-contamination in PCR and qPCR
      despite extensive use, greatly increased data reproducibility (large increases in
      data quality and Cq consistency), lowered reaction volumes for large cost
      savings, and nearly a magnitude increase in speed per instrument. We show several
      comparisons between traditional- and ADE-based pipetting for a qPCR-based
      workflow. 

PMID- 26311061
TI  - A Liquid-Handling Robot for Automated Attachment of Biomolecules to Microbeads.
AB  - Diagnostics, drug delivery, and other biomedical industries rely on cross-linking
      ligands to microbead surfaces. Microbead functionalization requires multiple
      steps of liquid exchange, incubation, and mixing, which are laborious and time
      intensive. Although automated systems exist, they are expensive and cumbersome,
      limiting their routine use in biomedical laboratories. We present a small, bench
      top robotic system that automates microparticle functionalization and streamlines
      sample preparation. The robot uses a programmable microcontroller to regulate
      liquid exchange, incubation, and mixing functions. Filters with a pore diameter
      smaller than the minimum bead diameter are used to prevent bead loss during
      liquid exchange. The robot uses three liquid reagents and processes up to 10(7)
      microbeads per batch. The effectiveness of microbead functionalization was
      compared with a manual covalent coupling process and evaluated via flow cytometry
      and fluorescent imaging. The mean percentages of successfully functionalized
      beads were 91% and 92% for the robot and manual methods, respectively, with less
      than 5% bead loss. Although the two methods share similar qualities, the
      automated approach required approximately 10 min of active labor, compared with 3
      h for the manual approach. These results suggest that a low-cost, automated
      microbead functionalization system can streamline sample preparation with minimal
      operator intervention. 

PMID- 26311063
TI  - Factors influencing big-bubble formation during deep anterior lamellar
      keratoplasty in keratoconus.
AB  - PURPOSE: To investigate recipient and operative factors that can influence the
      rate of achieving a bare Descemet's membrane (DM) during deep anterior lamellar
      keratoplasty (DALK) for keratoconus. MATERIALS: In this retrospective comparative
      study, a total of 290 (153 right) consecutive eyes from 257 (179 male)
      keratoconus-affected patients who underwent DALK with the big-bubble technique
      were enrolled. Univariate analyses and multiple logistic regressions were used to
      investigate factors including patient age and sex, family history of keratoconus,
      history of contact lens wear or vernal keratoconjunctivitis, the presence of
      Vogt's striae or superficial stromal opacities, keratometric readings, corneal
      diameter, central and peripheral corneal thickness, anterior chamber depth,
      vitreous length, and trephination size, which could predict achievement of a bare
      DM. RESULTS: The surgery was completed as a DALK in 289 of 290 eyes, and a bare
      DM was successfully achieved in 229 (79.2%) eyes. The recipient sex and
      trephination size significantly influenced the success rate of big-bubble
      formation. Females had decreased odds of achieving a bare DM by 0.44 times
      (p=0.02). For each 0.1 mm increase in the trephination size, the odds of a
      successful big-bubble formation increased by 1.36 times (p=0.03). Other
      investigated factors did not significantly influence the rate of achieving a bare
      DM. CONCLUSIONS: The rate of successful big-bubble formation was 79.2% in
      keratoconus. Among the different factors, recipient sex and trephination size
      significantly influenced this rate. Females had a lower probability of big-bubble
      formation, and a large trephination size was associated with an increase in the
      probability of achieving a bare DM.

PMID- 26311064
TI  - En face optical coherence tomography angiography for corneal neovascularisation.
AB  - BACKGROUND/AIM: Recently, there has been an increasing clinical need for
      objective evaluation of corneal neovascularisation, a condition which cause
      significant ocular morbidity. We describe the use of a rapid, non-invasive 'en
      face' optical coherence tomography angiography (OCTA) system for the assessment
      of corneal neovascularisation. METHODS: Consecutive patients with abnormal
      corneal neovascularisation were scanned using a commercially available AngioVue
      OCTA system (Optovue, Fremont, California, USA) with the split-spectrum amplitude
      decorrelation angiography algorithm, using an anterior segment lens adapter. Each
      subject had four scans in each eye by a trained operator and two independent
      masked assessors analysed all images. Main outcome measures were scan quality
      (signal strength, image quality), area of neovascularisation and repeatability of
      corneal vascular grade. RESULTS: We performed OCTA in 20 patients (11 men, 9
      women, mean age 49.27+/-17.23 years) with abnormal corneal neovascularisation.
      The mean area of corneal neovascularisation was 0.57+/-0.30 mm(2) with a mean
      neovascularisation grade of 3.5+/-0.2 in the OCTA scans. We found the OCTA to
      produce good quality images of the corneal vessels (signal strength: 36.95+/
      13.97; image quality score 2.72+/-1.07) with good repeatability for assessing
      neovascularisation grade (kappa=0.84). CONCLUSIONS: In this preliminary clinical
      study, we describe a method for acquiring angiography images with 'en face'
      views, using an OCTA system adapted for the evaluation of corneal
      neovascularisation. Further studies are required to compare the scans to other
      invasive angiography techniques for the quantitative evaluation of abnormal
      corneal vessels.

PMID- 26311062
TI  - Characterization of multinucleated giant cells in synovium and subchondral bone
      in knee osteoarthritis and rheumatoid arthritis.
AB  - BACKGROUND: Multinucleated giant cells have been noticed in diverse arthritic
      conditions since their first description in rheumatoid synovium. However, their
      role in the pathogenesis of osteoarthritis (OA) or rheumatoid arthritis (RA)
      still remains broadly unknown. We aimed to study the presence and characteristics
      of multinucleated giant cells (MGC) both in synovium and in subchondral bone
      tissues of patients with OA or RA. METHODS: Knee synovial and subchondral bone
      samples were from age-matched patients undergoing total joint replacement for OA
      or RA, or non-arthritic post mortem (PM) controls. OA synovium was stratified by
      histological inflammation grade using index tissue sections. Synovitis was
      assessed by Krenn score. Histological studies employed specific antibodies
      against macrophage markers or cathepsin K, or TRAP enzymatic assay. RESULTS:
      Inflamed OA and RA synovia displayed more multinucleated giant cells than did non
      inflamed OA and PM synovia. There was a significant association between MGC
      numbers and synovitis severity. A TRAP negative/cathepsin K negative Langhans
      like subtype was predominant in OA, whereas both Langhans-like and TRAP
      positive/cathepsin K-negative foreign-body-like subtypes were most commonly
      detected in RA. Plasma-like and foam-like subtypes also were observed in OA and
      RA synovia, and the latter was found surrounding adipocytes. TRAP
      positive/cathepsin K positive osteoclasts were only identified adjacent to
      subchondral bone surfaces. TRAP positive osteoclasts were significantly increased
      in subchondral bone in OA and RA compared to PM controls. CONCLUSIONS:
      Multinucleated giant cells are associated with synovitis severity, and
      subchondral osteoclast numbers are increased in OA, as well as in RA. Further
      research targeting multinucleated giant cells is warranted to elucidate their
      contributions to the symptoms and joint damage associated with arthritis.

PMID- 26311065
TI  - Changes in higher-order aberrations of intraocular lenses with intrascleral
      fixation.
AB  - AIM: To determine the higher-order aberrations of intraocular lenses (IOLs) that
      are extended and fixed intrasclerally. METHODS: A computer-aided design system
      was used to calculate the length of an IOL when it was fixed to the sclera 2 mm
      posterior to the limbus in a Gullstrand eye model. An acrylic single-piece
      (SA60AT) or 2 three-piece IOLs (VA-60BBR; X-60) were fixed at lengths of 13, 14,
      15 and 16 mm. A wavefront analyser was used to measure the higher-order
      aberrations within the central 3.0 and 5.2 mm optic diameters. RESULTS: The
      length of the IOL with the intrascleral fixation was calculated to be 13.9-14.9
      mm in the eye model. The astigmatic aberration of the three-piece VA-60BBR and X
      60 IOLs increased significantly with an extension of the IOLs within the central
      5.2 mm (both p<0.001) but not that of the single-piece SA60AT IOL. The coma
      aberration of the VA-60BBR IOL increased significantly within the central 5.2 mm
      with an increase in the extension (p=0.001) but not that of the SA60AT and X-60
      IOLs. The astigmatic and coma aberrations were significantly greater within the
      central 5.2 mm than within the central 3.0 mm for all IOLs (p<0.05). The
      cylindrical power increased from 0.034 D to 0.082 D with extensions from 13 to 16
      mm. CONCLUSIONS: When three-piece IOLs are extended widely for intrascleral
      fixation, the astigmatic and coma aberrations increase but the degree of change
      should not alter the postoperative vision appreciably.

PMID- 26311066
TI  - Rhizoma Paridis Saponins Induces Cell Cycle Arrest and Apoptosis in Non-Small
      Cell Lung Carcinoma A549 Cells.
AB  - BACKGROUND: As a traditional Chinese medicine herb, Chonglou (Paris polyphylla
      var. chensiins) has been used as anticancer medicine in China in recent decades,
      as it can induce cell cycle arrest and apoptosis in numerous cancer cells. The
      saponins extract from the rhizoma of Chonglou [Rhizoma Paridis saponins (RPS)] is
      known as the main active component for anticancer treatment. However, the
      molecular mechanism of the anticancer effect of RPS is unknown. MATERIAL AND
      METHODS: The present study evaluated the effect of RPS in non-small-cell lung
      cancer (NSCLC) A549 cells using the 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyl
      tetrazolium bromide (MTT) assay and flow cytometry. Subsequently, the expression
      of several genes associated with cell cycle and apoptosis were detected by
      reverse transcription-quantitative polymerase chain reaction (qRT-PCR) and
      Western blotting. RESULTS: RPS was revealed to inhibit cell growth, causing a
      number of cells to accumulate in the G 1 phase of the cell cycle, leading to
      apoptosis. In addition, the effect was dose-dependent. Moreover, the results of
      qRT-PCR and Western blotting showed that p53 and cyclin-dependent kinase 2 (CDK2)
      were significantly downregulated, and that BCL2, BAX, and p21 were upregulated,
      by RPS treatment. CONCLUSIONS: We speculated that the RPS could act on a pathway,
      including p53, p21, BCL2, BAX, and CDK2, and results in G1 cell cycle arrest and
      apoptosis in NSCLC cells.

PMID- 26311067
TI  - A simple procedure for directly obtaining haplotype sequences of diploid genomes.
AB  - BACKGROUND: Almost all genome sequencing projects neglect the fact that diploid
      organisms contain two genome copies and consequently what is published is a
      composite of the two. This means that the relationship between alternate alleles
      at two or more linked loci is lost. We have developed a simplified method of
      directly obtaining the haploid sequences of each genome copy from an individual
      organism. RESULTS: The diploid sequences of three groups of cattle samples were
      obtained using a simple sample preparation procedure requiring only a microscope
      and a haemocytometer. Samples were: 1) lymphocytes from a single Angus steer; 2)
      sperm cells from an Angus bull; 3) lymphocytes from East African Zebu (EAZ)
      cattle collected and processed in a field laboratory in Eastern Kenya. Haploid
      sequence from a fosmid library prepared from lymphocytes of an EAZ cow was used
      for comparison. Cells were serially diluted to a concentration of one cell per
      microlitre by counting with a haemocytometer at each dilution. One microlitre
      samples, each potentially containing a single cell, were lysed and divided into
      six aliquots (except for the sperm samples which were not divided into aliquots).
      Each aliquot was amplified with phi29 polymerase and sequenced. Contigs were
      obtained by mapping to the bovine UMD3.1 reference genome assembly and scaffolds
      were assembled by joining adjacent contigs that were within a threshold distance
      of each other. Scaffolds that appeared to contain artefacts of CNV or repeats
      were filtered out leaving scaffolds with an N50 length of 27-133 kb and a 88-98 %
      genome coverage. SNP haplotypes were assembled with the Single Individual
      Haplotyper program to generate an N50 size of 97-201 kb but only ~27-68 % genome
      coverage. This method can be used in any laboratory with no special equipment at
      only slightly higher costs than conventional diploid genome sequencing. A
      substantial body of software for analysis and workflow management was written and
      is available as supplementary data. CONCLUSIONS: We have developed a set of
      laboratory protocols and software tools that will enable any laboratory to obtain
      haplotype sequences at only modestly greater cost than traditional mixed diploid
      sequences.

PMID- 26311069
TI  - Pseudomonas aeruginosa essentials: an update on investigation of essential genes.
AB  - Pseudomonas aeruginosa is the leading cause of nosocomial infections,
      particularly in immunocompromised, cancer, burn and cystic fibrosis patients.
      Development of novel antimicrobials against P. aeruginosa is therefore of the
      highest importance. Although the first reports on P. aeruginosa essential genes
      date back to the early 2000s, a number of more sensitive genomic approaches have
      been used recently to better define essential genes in this organism. These
      analyses highlight the evolution of the definition of an 'essential' gene from
      the traditional to the context-dependent. Essential genes, particularly those
      indispensable under the clinically relevant conditions, are considered to be
      promising targets of novel antibiotics against P. aeruginosa. This review
      provides an update on the investigation of P. aeruginosa essential genes. Special
      focus is on recently identified P. aeruginosa essential genes and their
      exploitation for the development of antimicrobials. 

PMID- 26311068
TI  - Loss of Weight in Obese Older Adults: A Biomarker of Impending Expansion of
      Multimorbidity?
AB  - OBJECTIVES: To determine whether weight loss in older adults may be a marker of
      impending burden of multimorbidity regardless of initial weight, testing the
      hypotheses that obesity but not overweight in elderly adults is associated with
      greater number of diseases than normal weight and that obese older adults who
      lose weight over time have the greatest burden of multimorbidity. DESIGN:
      Longitudinal cohort study (Invecchiare in Chianti Study). SETTING: Community.
      PARTICIPANTS: Individuals aged 60 and older at baseline followed for an average
      of 4 years (N = 1,025). MEASUREMENTS: Multimorbidity was measured as number of
      diagnosed diseases. Baseline body mass index (BMI) was categorized as normal
      weight (<25.0 kg/m(2)), overweight (25.0-29.9 kg/m(2)), and obese (>=30.0
      kg/m(2)). Loss of weight was defined as decrease over time in BMI of at least
      0.15 kg/m(2) per year. Age, sex, and education were covariates. RESULTS: Baseline
      obesity was cross-sectionally associated with high multimorbidity and greater
      longitudinal increase of multimorbidity than normal weight (P = .005) and
      overweight (P < .001). Moreover, obese participants who lost weight over follow
      up had a significantly greater increase in multimorbidity than other
      participants, including obese participants who maintained or gained weight over
      time (P = .005). In nonobese participants, changes in weight had no effect on
      changes in multimorbidity over time. Sensitivity analyses confirmed that one
      specific disease did not drive the association and that competing mortality did
      not bias the association. CONCLUSION: Loss of weight in obese older persons is a
      strong biomarker of impending expansion of multimorbidity. Older obese
      individuals who lose weight should receive thoughtful medical attention.

PMID- 26311070
TI  - Growth restriction and gender influence cerebral oxygenation in preterm neonates.
AB  - OBJECTIVE: To investigate the effect of fetal growth restriction and gender on
      cerebral oxygenation in preterm neonates during the first 3 days of life. DESIGN:
      Case-control study. SETTING: Neonatal Intensive Care Unit of the Wilhelmina
      Children's Hospital, The Netherlands. PATIENTS: 68 (41 males) small for
      gestational age (SGA) (birth weight <10th percentile) and 136 (82 males)
      appropriate for gestational age (AGA) (birth weight 20th-80th percentile)
      neonates, matched for gender, gestational age, ventilatory and blood pressure
      support. METHODS: Regional cerebral oxygen saturation (rScO2) and cerebral
      fractional tissue oxygen extraction (cFTOE) as measured by near-infrared
      spectroscopy throughout the first 72 h of life were compared between SGA and AGA
      neonates. The effect of gender was also explored within these comparisons.
      RESULTS: SGA neonates demonstrated higher rScO2 (71% SEM 0.2 vs 68% SEM 0.2) and
      lower cFTOE (0.25 SEM 0.002 vs 0.29 SEM 0.002) than AGA neonates. There was an
      independent effect of gender on rScO2 and cFTOE, resulting in the finding that
      SGA males displayed highest rScO2 and lowest cFTOE (73% SEM 0.3 respectively 0.24
      SEM 0.003). AGA males and SGA females showed comparable rScO2 (69% SEM 0.2 vs 69%
      SEM 0.4) and cFTOE (0.28 SEM 0.002 vs 0.28 SEM 0.004). AGA females showed lowest
      rScO2 and highest cFTOE (66% SEM 0.2 respectively 0.30 SEM 0.002). CONCLUSIONS:
      Growth restriction and gender influence cerebral oxygenation and oxygen
      extraction in preterm neonates throughout the first 3 days of life.

PMID- 26311071
TI  - Evidence for accelerated tauopathy in the retina of transgenic P301S tau mice
      exposed to repetitive mild traumatic brain injury.
AB  - Chronic traumatic encephalopathy (CTE) is associated with repetitive mild
      traumatic brain injury (mTBI) in the context of contact and collision sports, but
      not all exposed individuals develop this condition. In addition, experiments in
      animal models in several laboratories have shown that non-transgenic mice do not
      develop tauopathy after exposure to repetitive mTBI schedules. It is thus
      reasonable to assume that genetic factors may play an etiological role in the
      development of CTE. More than 40 mutations in the tau gene are known to confer
      proneness to aggregation and are thought to cause neurodegenerative diseases
      including frontotemporal degeneration (FTD). Transgenic mice harboring these
      mutations can be used to ask the question whether repetitive mTBI can accelerate
      onset and course of tauopathy or worsen the outcomes of transgenic disease. In
      this study, we exposed mice harboring the tau P301S transgene associated with FTD
      to repetitive mTBI schedules by impact acceleration (IA) that we have previously
      characterized. We explored the progression of tauopathy in the retina and
      neocortex based on density of neuronal profiles loaded with tau pS422, a marker
      of advanced tau hyperphosphorylation. We found that the density of tau pS422 (+)
      retinal ganglion cells (RGCs) increased twenty fold with one mTBI hit, a little
      over fifty fold with four mTBI hits and sixty fold with 12 mTBI hits. The
      severity of mTBI burden (number of hits) was a significant factor in tauopathy
      outcome. On the other hand, we found no association between repetitive mTBI and
      density of pS422 (+) neuronal profiles in neocortex, a region that is not
      featured by significant TAI in our repetitive mTBI model. We observed similar,
      but less prominent, trends in tauopathy-prone transgenic mice harboring all 6
      isoforms of wild-type human tau without mouse tau. Our findings indicate that
      repetitive mTBI accelerates tauopathy under diverse genetic conditions
      predisposing to tau aggregation and suggest a vulnerability-stress model in
      understanding some cases of acquired neurodegenerative disease after repetitive
      mTBI. 

PMID- 26311072
TI  - Long term exposure to antiangiogenic therapy, bevacizumab, induces osteonecrosis.
AB  - PURPOSE: Bevacizumab, a monoclonal VEGF-A antibody, has been identified as an
      aetiology of osteonecrosis of the femoral head. Long exposure to anti VEGF
      therapy induced chronic hypoperfusion of normal tissues. Osteonecrosis is a
      musculo-skeletal disease secondary to cellular death of bone component mainly
      induced by corticosteroids, alcohol use, or connective tissue disorders. METHODS:
      The medical records of patients with metastatic colorectal carcinoma receiving
      Bevacizumab between January 2006 and November 2013 were retrospectively reviewed
      and we had looked for osteonecrosis. Every disorder of musculoskeletal mobility
      were examined by orthopaedist and evaluated by imaging. RESULTS: We report on
      osteonecrosis of humeral and femoral head in patient with metastatic colon
      adenocarcinoma receiving a long-term exposure to anti angiogenic based treatment
      (>6 months), lack of other factors predisposing to osteonecrosis. These
      observations, according to literature, suggests that long exposure to anti VEGF
      A, Bevacizumab, promote bone hypoperfusion and may induced osteonecrosis either
      on the femoral head or the humeral head with an incidence of 4 out of 1000
      patients. CONCLUSIONS: With an incidence of 4 out of 1000 patients osteonecrosis
      is a rare side effect of anti-angiogenic agent. With the increasing utilisation
      and duration of exposure of anti-VEGF therapy some rare side effect due to
      chronic ischemia may appear. The clinician should be aware about uncommon
      symptoms.

PMID- 26311073
TI  - Reactivity of a Nickel(II) Bis(amidate) Complex with meta-Chloroperbenzoic Acid:
      Formation of a Potent Oxidizing Species.
AB  - Herein, we report the formation of a highly reactive nickel-oxygen species that
      has been trapped following reaction of a Ni(II) precursor bearing a macrocyclic
      bis(amidate) ligand with meta-chloroperbenzoic acid (HmCPBA). This compound is
      only detectable at temperatures below 250 K and is much more reactive toward
      organic substrates (i.e., C-H bonds, C=C bonds, and sulfides) than previously
      reported well-defined nickel-oxygen species. Remarkably, this species is formed
      by heterolytic O-O bond cleavage of a Ni-HmCPBA precursor, which is concluded
      from experimental and computational data. On the basis of spectroscopy and DFT
      calculations, this reactive species is proposed to be a Ni(III) -oxyl compound.

PMID- 26311074
TI  - Alzheimer's disease: rare variants with large effect sizes.
AB  - Recent advances in sequencing technology and novel genotyping arrays (focused on
      low-frequency and coding variants) have made it possible to identify novel coding
      variants with large effect sizes and also novel genes (TREM2, PLD3, UNC5C, and
      AKAP9) associated with Alzheimer's disease (AD) risk. The major advantages of
      these studies over the classic genome-wide association studies (GWAS) include the
      identification of the functional variant and the gene-driven association. In
      addition to the large effect size, these studies make it possible to model these
      variants and genes using cell and animal systems. On the other hand, the
      underlying population-variability of these very low allele frequency variants
      poses a great challenge to replicating results. Studies that include very large
      datasets (>10,000 cases and controls) and combine sequencing and genotyping
      approaches will lead to the identification of novel genes for Alzheimer's
      disease. 

PMID- 26311076
TI  - Methylation of the DCLK1 promoter region in circulating free DNA and its
      prognostic value in lung cancer patients.
AB  - INTRODUCTION: The possibility of detection of suppressor genes methylation in
      circulating free DNA (cf-DNA) of cancer patients and the lack of methylation in
      healthy individuals makes this epigenetic alternation an ideal diagnostic marker
      of neoplastic processes. Moreover, hypermethylation in several genes promoter was
      described as a biomarker of lung cancer. Methylation in the gene encoding
      doublecortin-like kinase 1 (DCLK1) is observed in patients with colorectal cancer
      and cholangiocarcinoma. However, there are no studies concerning DCLK1
      methylation in lung cancer patients. The aims of the study was to evaluate the
      frequency of DCLK1 promoter methylation in cf-DNA of lung cancer patients and of
      healthy persons as well as the usefulness of this test for predicting the lung
      cancer course. MATERIALS AND METHODS: DCLK1 methylation status was evaluated in
      DNA isolated from peripheral blood plasma from 65 lung cancer patients and 95
      healthy individuals. After DNA bisulfitation, DCLK1 methylation was determined
      using the qMSP-PCR technique. Moreover, the presence of DCLK1 methylation was
      correlated with the overall survival (OS) probability of lung cancer patients.
      RESULTS: DCLK1 promoter methylation was detected in 32 lung cancer patients (49.2
      %) and 8 healthy individuals (8.4 %). The methylation of the region before
      transcription start site (TSS) and the region after TSS of DCLK1 gene was
      detected in 28 and 11 patients, respectively. In seven cases (10.8 %), the DCLK1
      promoter methylation in both regions was reported simultaneously. The methylation
      was observed slightly frequently in patients with small cell lung cancer (75 % of
      SCLC patients). The median overall survival of patients with DCLK1 promoter
      methylation was lower than that of patients without DCLK1 gene modification (p =
      <0.001, HR = 4.235). CONCLUSIONS: The evaluation of DCLK1 promoter region
      methylation may be useful in both early diagnosis and prediction of the course of
      lung cancer.

PMID- 26311078
TI  - Bone marrow trephine biopsy involvement by lymphoma: pattern of involvement and
      concordance with flow cytometry, in 10 years from a single institution.
AB  - PURPOSE: To evaluate the features of bone marrow (BM) biopsy involvement by
      lymphoma, pattern of infiltration, morphological analysis and flow cytometry were
      reviewed at all lymphoma patients over a period of 10 years. METHODS/PATIENTS:
      413 cases were included in the study if BM biopsy slides were available. Only 356
      patients had both BM trephine biopsy and flow cytometry. RESULTS: The most
      frequent subtype was diffuse large B cell (31.2%), followed by follicular
      lymphoma (18.9%). The predominant pattern was mixed (nodular-interstitial)
      (9.2%). Morphological marrow infiltration was found in 138 cases, and flow
      cytometry identified 117 cases with BM involvement. A concordance between the two
      methods was detected in 305 cases (85.7%). There was discordance in 51 cases
      (14.3%): morphology positive/FC negative in 33 cases and morphology negative/FC
      positive in 18. CONCLUSIONS: Flow cytometry is slightly more useful in detecting
      involvement when the BM is affected, but this finding is not conclusive.

PMID- 26311077
TI  - The effect of slice thickness on target and organs at risk volumes, dosimetric
      coverage and radiobiological impact in IMRT planning.
AB  - PURPOSE: Dose-volume histogram (DVH) has become an important tool for evaluation
      of radiation outcome as reflected from many clinical protocols. While dosimetric
      accuracy in treatment planning system (TPS) is well quantified, the variability
      in volume estimation is uncertain due to reconstruction algorithm that is
      investigated in this study. In addition, the impact of dose distribution and
      tumor control probability (TCP) were also investigated with CT slice thickness
      for IMRT planning. MATERIALS AND METHODS: A water phantom containing various
      objects with accurately known volume ranging from 1 to 100 cm(3) was scanned with
      1, 2, 3, 5, and 10 mm slice thickness. The CT data sets were sent to Eclipse TPS
      for contour delineation and volume estimation. The data were compared with known
      volume for the estimation of error in the volume of each structure. IMRT Plans
      were generated on phantom containing four objects with different slice thickness
      (1-5 mm) to calculate TCP. ICRU-83-recommended dose points such as D 2%, D 50%, D
      98%, as well as homogeneity and conformity index were also calculated. RESULTS:
      The variability of volumes with CT slice thickness was significant especially for
      small volume structures. A maximum error of 92% was noticed for 1 cm(3) volume of
      object with 10 mm slice thickness, whereas it was ~19% for 1 mm slice thickness.
      For 2 and 3 cm(3) objects, the maximum error of 99% was noticed with 10 mm slice
      thickness and ~60% with 5 mm. The differences are smaller for larger volumes with
      a cutoff at about 20 cm(3). The calculated volume of the objects is a function of
      reconstruction algorithm and slice thickness. The PTV mean dose and TCP decreased
      with increasing slice thickness. Maximum variation of ~5% was noticed in mean
      dose and ~2% in TCP with change in slice thickness from 1 to 5 mm. The relative
      decrease in target volume receiving 95% of the prescribed dose is ~5% with change
      in slice thickness from 1 to 5 mm. The homogeneity index increases up to 163% and
      conformity index decreases by 4% between 1 and 5 mm slice thickness, producing
      highly inhomogeneous and least conformal treatment plan. CONCLUSIONS: Estimation
      of a volume is dependent on CT slice thickness and the contouring algorithm in a
      TPS. During commissioning of TPS and for all clinical protocols, evaluation of
      volume should be included to provide the limit of accuracy in DVH from TPS,
      especially for small objects. A smaller slice thickness provides superior
      dosimetry with improved TCP. Thus, the smallest possible slice thickness should
      be used for IMRT planning, especially when smaller structures are present.

PMID- 26311079
TI  - Clinical target volume in postoperative radiotherapy for gastric cancer:
      identification of major difficulties and controversies.
AB  - PURPOSE: To identify the main difficulties in postoperative clinical target
      volume (CTV) delineation in gastric cancer (GC). METHODS: Before and after a
      training course, 20 radiation oncology residents were asked to delineate the CTV
      for the postoperative GC case on four computed tomography scans: dome of the
      diaphragm, anterior abdominal wall, duodenal stump and porta hepatis level, and
      to determine the lower CTV border. CTV volume was reconstructed from requested
      planar contours. Area of intersection (AI) for each requested scan and volume of
      intersection (VI), defined as the overlap of delineated area/volume with
      respective reference area (RA)/reference volume (RV) proposed by the senior
      radiation oncologist, were computed. The degree of agreement between the
      reference and participants' contours was quantified using the Concordance Index
      (CI): AI/RA * 100% or VI/RV * 100%. The lower CTV border was analyzed separately.
      Pre- and post-training CIs were compared. A questionnaire investigated the
      difficulties with contouring. RESULTS: Mean CI value was the lowest for the dome
      of the diaphragm (24% pre-training, 35 % post-training) and for the duodenal
      stump (49% pre-training, 61% post-training). Mean CI for the CTV volume was 49%
      pre-training and 59% post-training, p = 0.39. Mean distance from the reference to
      the participants' lower CTV borders was 2.73 cm pre-training and 2.0 cm post
      training, p = 0.71. In a questionnaire, 75% of respondents indicated the elective
      nodal area as the main difficulty. CONCLUSIONS: Delineation of the dome of the
      diaphragm and the duodenal stump, as yet not recognized as the source of
      variation, should be addressed in the international consensus guidelines and
      clarified.

PMID- 26311075
TI  - Activation of Neuropeptide Y Receptors Modulates Retinal Ganglion Cell Physiology
      and Exerts Neuroprotective Actions In Vitro.
AB  - Neuropeptide Y (NPY) is expressed in mammalian retina but the location and
      potential modulatory effects of NPY receptor activation remain largely unknown.
      Retinal ganglion cell (RGC) death is a hallmark of several retinal degenerative
      diseases, particularly glaucoma. Using purified RGCs and ex vivo rat retinal
      preparations, we have measured RGC intracellular free calcium concentration
      ([Ca2+]i) and RGC spiking activity, respectively. We found that NPY attenuated
      the increase in the [Ca2+]i triggered by glutamate mainly via Y1 receptor
      activation. Moreover, (Leu31, Pro34)-NPY, a Y1/Y5 receptor agonist, increased the
      initial burst response of OFF-type RGCs, although no effect was observed on RGC
      spontaneous spiking activity. The Y1 receptor activation was also able to
      directly modulate RGC responses by attenuating the NMDA-induced increase in RGC
      spiking activity. These results suggest that Y1 receptor activation, at the level
      of inner or outer plexiform layers, leads to modulation of RGC receptive field
      properties. Using in vitro cultures of rat retinal explants exposed to NMDA, we
      found that NPY pretreatment prevented NMDA-induced cell death. However, in an
      animal model of retinal ischemia-reperfusion injury, pretreatment with NPY or
      (Leu31, Pro34)-NPY was not able to prevent apoptosis or rescue RGCs. In
      conclusion, we found modulatory effects of NPY application that for the first
      time were detected at the level of RGCs. However, further studies are needed to
      evaluate whether NPY neuroprotective actions detected in retinal explants can be
      translated into animal models of retinal degenerative diseases.

PMID- 26311080
TI  - Predictive performance of Vancomycin population pharmacokinetic models in Iranian
      patients underwent hematopoietic stem cell transplantation.
AB  - OBJECTIVE: Many hematopoietic stem cell transplantation (HSCT) patients receive
      vancomycin empirically during febrile neutropenia. There are several models for
      estimation of vancomycin pharmacokinetic parameters and calculation of initial
      dosing regimen accordingly. However, the performance of these methods in HSCT
      patients remained to be evaluated. The aim of the study was to determine which of
      the vancomycin population pharmacokinetic methods best fit Iranian HSCT patients.
      METHODS: In order to evaluate predicted performance of seven vancomycin
      population pharmacokinetic models, the pharmacokinetic parameters of patients
      were estimated using each model's equations. Then the predicted steady-state
      trough vancomycin concentration was calculated based on each model's parameters
      and using a formula based on Sawchuk-Zaske method. The predicted steady-state
      trough vancomycin concentration and the real measured concentrations were
      compared to see which method was the most precise and least biased using mean
      squared error (MSE) and mean prediction error (ME) respectively. FINDINGS: Forty
      six patients (65% men) were included in the study. Calculated metrics showed a
      range of 38% under-prediction bias with Rodvold to 34% over-prediction bias with
      Matzke and Burton models. Birt and revised Burton methods showed no significant
      bias (ME [95% confidence interval (CI)]: -0.067 [-0.235-0.101] and 0.066 [-0.105
      0.238]). Birt and revised Burton were not different significantly considering MSE
      (95% CI) of 0.385 (0.227-0.544) and 0.401 (0.255-0.546), respectively.
      Comparisons of precision with naive predictors revealed a delta MSE (95% CI) of 
      0.128 (-1.379-1.890) for Birt and 0.026 (-0.596-0.940) for revised Burton models.
      CONCLUSION: Although the Birt and Burton revised methods performed well, none of
      the studied models showed acceptable performance to be implemented as a routine
      method for initial dose calculation in HSCT patients. A vancomycin
      pharmacokinetic model specific for this high-risk subpopulation of Iranian
      patients should be designed and validated.

PMID- 26311081
TI  - The Halls Creek Community Families Program: Elements of the role of the child
      health nurse in development of a remote Aboriginal home visiting peer support
      program for families in the early years.
AB  - OBJECTIVE: To undertake an evaluation of elements of the role of the child health
      nurse in the development of peer support for Aboriginal families with young
      children in a remote setting. DESIGN: The Halls Creek Community Families Program
      uses expertise of peer support workers to support parents of young families. In
      stage one, participatory action research was used. The program facilitator, who
      was a child health nurse, undertook action learning sets where issues were
      explored relating to home visiting strategies to families. Additionally, the
      facilitator maintained a reflective practice diary. Outcomes contributed to stage
      two, where an independent researcher evaluated program changes.This report
      relates to stage one, which used descriptive qualitative data from interviews
      with peer support workers and community support agencies, and the facilitator's
      reflective diary. Data were analysed by thematic analysis, focusing on elements
      of the role of the facilitator in program development. SETTING: A remote
      Aboriginal community in the Kimberley region of Western Australia. PARTICIPANTS:
      Eight peer support workers and five health and welfare professionals from
      community support agencies. MAIN OUTCOME MEASURES: This study measures changes in
      participants' understanding of the role and scope of practice of the child health
      nurse facilitator, thereby supporting improved support for Aboriginal families
      with young children. RESULTS: Thematic analysis identified three major changes in
      understanding the child health nurse facilitator role: working in partnership,
      communication strategies and education and organisational strategies. CONCLUSION:
      Findings suggest empowering benefits for Aboriginal peer support workers from the
      facilitating role of the child health nurse.

PMID- 26311082
TI  - Prenatal diagnosis of total arhinia by MRI.
AB  - Congenital arhinia is the absence of an external nose, nasal cavities and
      olfactory apparatus, and extremely rare. It occurs during the early gestational
      stage and may be a result of maldevelopment of the paired nasal placodes
      embryologically. Total arhinia is often associated with other craniofacial
      abnormalities. Early detection may be helpful for the parents and physician.
      However, fewer than 40 patients with arhinia have been reported so far, and most
      of them were diagnosed after birth. To our knowledge, this is the first case
      diagnosed by fetal MRI during the second trimester of pregnancy, and confirmed by
      pathological examination. 

PMID- 26311083
TI  - Field versus laboratory experiments to evaluate the fate of azoxystrobin in an
      amended vineyard soil.
AB  - This study reports the effect that adding spent mushroom substrate (SMS) to a
      representative vineyard soil from La Rioja region (Spain) has on the behaviour of
      azoxystrobin in two different environmental scenarios. Field dissipation
      experiments were conducted on experimental plots amended at rates of 50 and 150 t
      ha(-1), and similar dissipation experiments were simultaneously conducted in the
      laboratory to identify differences under controlled conditions. Azoxystrobin
      dissipation followed biphasic kinetics in both scenarios, although the initial
      dissipation phase was much faster in the field than in the laboratory
      experiments, and the half-life (DT50) values obtained in the two experiments were
      0.34-46.3 days and 89.2-148 days, respectively. Fungicide residues in the soil
      profile increased in the SMS amended soil and they were much higher in the top
      two layers (0-20 cm) than in deeper layers. The persistence of fungicide in the
      soil profile is consistent with changes in azoxystrobin adsorption by unamended
      and amended soils over time. Changes in the dehydrogenase activity (DHA) of soils
      under different treatments assayed in the field and in the laboratory indicated
      that SMS and the fungicide had a stimulatory effect on soil DHA. The results
      reveal that the laboratory studies usually reported in the literature to explain
      the fate of pesticides in amended soils are insufficient to explain azoxystrobin
      behaviour under real conditions. Field studies are necessary to set up efficient
      applications of SMS and fungicide, with a view to preventing the possible risk of
      water contamination.

PMID- 26311084
TI  - Comparison of the efficiencies of attached- versus suspended-growth SBR systems
      in the treatment of recycled paper mill wastewater.
AB  - The complexity of residual toxic organics from biologically treated effluents of
      pulp and paper mills is a serious concern. To date, it has been difficult to
      choose the best treatment technique because each of the available options has
      advantages and drawbacks. In this study, two different treatment techniques using
      laboratory-scale aerobic sequencing batch reactors (SBRs) were tested with the
      same real recycled paper mill effluent to evaluate their treatment efficiencies.
      Two attached-growth SBRs using granular activated carbon (GAC) with and without
      additional biomass and a suspended-growth SBR were used in the treatment of real
      recycled paper mill effluent at a chemical oxygen demand (COD) level in the range
      of 800-1300 mg/L, a fixed hydraulic retention time of 24 h and a COD:N:P ratio of
      approximately 100:5:1. The efficiency of this biological treatment process was
      studied over a 300-day period. The six most important wastewater quality
      parameters, namely, chemical oxygen demand (COD), turbidity, ammonia (expressed
      as NH3-N), phosphorus (expressed as PO4(3)-P), colour, and suspended solids (SS),
      were measured to compare the different treatment techniques. It was determined
      that these processes were able to almost completely and simultaneously eliminate
      COD (99%) and turbidity (99%); the removals of NH3-N (90-100%), PO4(3)-P (66
      78%), colour (63-91%), and SS (97-99%) were also sufficient. The overall
      performance results confirmed that an attached-growth SBR system using additional
      biomass on GAC is a promising configuration for wastewater treatment in terms of
      performance efficiency and process stability under fluctuations of organic load.
      Hence, this hybrid system is recommended for the treatment of pulp and paper mill
      effluents. 

PMID- 26311085
TI  - Perspectives of phytoremediation using water hyacinth for removal of heavy
      metals, organic and inorganic pollutants in wastewater.
AB  - The development of eco-friendly and efficient technologies for treating
      wastewater is one of the attractive research area. Phytoremediation is considered
      to be a possible method for the removal of pollutants present in wastewater and
      recognized as a better green remediation technology. Nowadays the focus is to
      look for a sustainable approach in developing wastewater treatment capability.
      Water hyacinth is one of the ancient technology that has been still used in the
      modern era. Although, many papers in relation to wastewater treatment using water
      hyacinth have been published, recently removal of organic, inorganic and heavy
      metal have not been reviewed extensively. The main objective of this paper is to
      review the possibility of using water hyacinth for the removal of pollutants
      present in different types of wastewater. Water hyacinth is although reported to
      be as one of the most problematic plants worldwide due to its uncontrollable
      growth in water bodies but its quest for nutrient absorption has provided way for
      its usage in phytoremediation, along with the combination of herbicidal control,
      integratated biological control and watershed management controlling nutrient
      supply to control its growth. Moreover as a part of solving wastewater treatment
      problems in urban or industrial areas using this plant, a large number of useful
      byproducts can be developed like animal and fish feed, power plant energy
      (briquette), ethanol, biogas, composting and fiber board making. In focus to the
      future aspects of phytoremediation, the utilization of invasive plants in
      pollution abatement phytotechnologies can certainly assist for their sustainable
      management in treating waste water. 

PMID- 26311086
TI  - Neighbourhood-scale urban forest ecosystem classification.
AB  - Urban forests are now recognized as essential components of sustainable cities,
      but there remains uncertainty concerning how to stratify and classify urban
      landscapes into units of ecological significance at spatial scales appropriate
      for management. Ecosystem classification is an approach that entails quantifying
      the social and ecological processes that shape ecosystem conditions into logical
      and relatively homogeneous management units, making the potential for ecosystem
      based decision support available to urban planners. The purpose of this study is
      to develop and propose a framework for urban forest ecosystem classification
      (UFEC). The multifactor framework integrates 12 ecosystem components that
      characterize the biophysical landscape, built environment, and human population.
      This framework is then applied at the neighbourhood scale in Toronto, Canada,
      using hierarchical cluster analysis. The analysis used 27 spatially-explicit
      variables to quantify the ecosystem components in Toronto. Twelve ecosystem
      classes were identified in this UFEC application. Across the ecosystem classes,
      tree canopy cover was positively related to economic wealth, especially income.
      However, education levels and homeownership were occasionally inconsistent with
      the expected positive relationship with canopy cover. Open green space and
      stocking had variable relationships with economic wealth and were more closely
      related to population density, building intensity, and land use. The UFEC can
      provide ecosystem-based information for greening initiatives, tree planting, and
      the maintenance of the existing canopy. Moreover, its use has the potential to
      inform the prioritization of limited municipal resources according to ecological
      conditions and to concerns of social equity in the access to nature and
      distribution of ecosystem service supply. 

PMID- 26311087
TI  - The effect of simple nitrogen fertilizer recommendation strategies on product
      carbon footprint and gross margin of wheat and maize production in the North
      China Plain.
AB  - Overuse of nitrogen (N) fertilizer constitutes the major issue of current crop
      production in China, exerting a substantial effect on global warming through
      massive emission of greenhouse gas (GHG). Despite the ongoing effort, which
      includes the promotion of technologically sophisticated N management schemes,
      farmers' N rates maintain at excessive rates. Therefore the current study tests
      three simple and easily to apply N fertilizer recommendation strategies, which
      could be implemented on large scale through the existing agricultural advisory
      system of China, at comparatively low cost. Building on a detailed crop
      production dataset of 65 winter wheat (WW) and summer maize (SM) producing farm
      households of the North China Plain, scenario analysis is applied. The effects of
      the three N strategies under constant and changing yield levels on product carbon
      footprint (PCF) and gross margin (GM) are determined for the production condition
      of every individual farm household. The N fixed rate strategy realized the
      highest improvement potential in PCF and GM in WW; while the N coefficient
      strategy performed best in SM. The analysis furthermore revealed that improved N
      management has a significant positive effect on PCF, but only a marginal and
      insignificant effect on GM. On the other side, a potential 10% yield loss would
      have only a marginal effect on PCF, but a detrimental effect on farmers' income.
      With farmers currently applying excessive N rates as "cheap insurance" against
      potential N limitation, it will be of vital importance to avoid any yield
      reductions (caused by N limitation) and respective severe financial losses, when
      promoting and implementing advanced fertilization strategies. To achieve this, it
      is furthermore recommended to increase the price of fertilizer, improve the
      agricultural extensions system, and recognize farmers' fertilizer related
      decision-making processes as key research areas. 

PMID- 26311088
TI  - Increased prevalence of diabetes mellitus and the metabolic syndrome in patients
      with primary aldosteronism of the German Conn's Registry.
AB  - DESIGN: Abnormalities in glucose homeostasis have been described in patients with
      primary aldosteronism (PA) but most studies show inconsistent results. Therefore,
      we aimed to compare the prevalence of type 2 diabetes mellitus and metabolic
      syndrome (MetS) in newly diagnosed PA patients to a matched control cohort of the
      background population. METHODS: In total, 305 PA patients of the prospective
      German Conn's Registry were compared to the population-based Study of Health In
      Pomerania (SHIP1; n=2454). A 1:1 match regarding sex, age, and BMI resulted in
      269 matched pairs regarding type 2 diabetes and 183 matched pairs regarding MetS.
      Of the total, 153 PA patients underwent oral glucose tolerance testing (OGTT) at
      diagnosis and 38 PA patients were reevaluated at follow-up. RESULTS: Type 2
      diabetes and MetS were significantly more frequent in PA patients than in the
      control population (17.2% vs 10.4%, P=0.03; 56.8% vs 44.8%, P=0.02 respectively).
      Also, HbA1c levels were higher in PA patients than in controls (P<0.01). Of the
      total, 35.3% of non-diabetic PA patients showed an abnormal OGTT (1/4 newly
      diagnosed type 2 diabetes and 3/4 impaired glucose tolerance). PA patients with
      an abnormal OGTT at baseline presented with significantly improved 2 h OGTT
      glucose (P=0.01) at follow-up. We detected a negative correlation between 2 h
      OGTT glucose levels and serum potassium (P<0.01). CONCLUSIONS: Type 2 diabetes
      and MetS are more prevalent in patients with PA than in controls matched for sex,
      age, BMI, and blood pressure. This may explain in part the increased
      cardiovascular disease morbidity and mortality in PA patients.

PMID- 26311089
TI  - Screw needle cytology of thyroid nodules is associated with a lower non
      diagnostic rate compared to fine needle aspiration.
AB  - BACKGROUND: Fine needle aspiration (FNA) cytology is the method of choice to
      exclude malignancy in thyroid nodules. A major limitation of thyroid FNA is the
      relatively high rate (13-17%) of non-diagnostic samples. The aim of this study is
      to determine the diagnostic yield of a screw needle compared to the conventional
      FNA. METHODS: We retrospectively analysed thyroid nodule cytology of all patients
      that underwent thyroid nodule fine needle or screw needle aspiration between July
      2007 and July 2012 in a single academic medical centre. Cytology results were
      categorized according to the Bethesda classification system. RESULTS: In total,
      644 punctures of thyroid nodules from 459 patients were available for analysis.
      The screw needle was used 531 times, and the conventional fine needle 113 times.
      The percentage of non-diagnostic cytology was significantly lower in the screw
      needle samples than in the fine needle samples (3% vs 17%, P<0.001). CONCLUSION:
      This study shows a significantly better diagnostic performance of the screw
      needle compared to the conventional fine needle in cytology of thyroid nodules.

PMID- 26311090
TI  - Oxidative stress and antioxidant levels in patients with anorexia nervosa: A
      systematic review and exploratory meta-analysis.
AB  - OBJECTIVE: To systematically review and meta-analyze oxidative stress and
      antioxidant markers in anorexia nervosa (AN). METHODS: Electronic PubMed search
      from database inception until 12/31/2013. Out of 1062 hits, 29 studies comparing
      oxidative stress/antioxidant markers between patients with AN and healthy
      controls (HCs) with a total of 1,729 participants (AN = 895, HCs = 834) were
      eligible. Data about oxidative stress and antioxidant markers, independent of
      their source, were extracted. We calculated random effects standardized mean
      differences (SMDs) as effect size measures for outcomes reported in >=5 studies;
      others were summarized descriptively. RESULTS: Compared to HCs, AN patients
      showed significantly higher apolipoprotein B (ApoB) levels (studies = 7; n = 551;
      SMD = 0.75; p = .0003, I(2)  = 74%), with higher age being associated with higher
      ApoB (Coefficient: 0.61 +/- 0.15, p < .0001), whereas BMI (p = .15) and
      measurement method (p = .70) did not moderate the results. Serum albumin levels
      were similar between AN and HCs (studies = 13; n = 509; SMD =-0.19; 95%CI: -0.62
      to 0.24; p = .38; I(2)  = 81%), with neither age (p = .84) nor BMI (p = .52)
      being significant moderators. Lower superoxide dismutase levels were reported in
      2 studies, while findings for vitamin A and its metabolites were inconclusive. In
      single studies, patients with AN had significantly higher catalase and nitric
      oxide (NO) parameter levels (platelet NO, exhaled NO and nitrites), such as lower
      glutathione and free cysteine levels, compared to HCs. DISCUSSION: AN appears to
      be associated with some markers of increased oxidative stress. Additional
      research is needed to discern whether oxidative stress is a potential cause or
      effect of AN, and whether treatments improving oxidative stress could be useful
      in AN.

PMID- 26311091
TI  - Effects of Dietary Genistein on Plasma and Liver Lipids, Hepatic Gene Expression,
      and Plasma Metabolic Profiles of Hamsters with Diet-Induced Hyperlipidemia.
AB  - Male hamsters were fed one of the following three diets for 6 weeks (n = 15):
      normal-fat diet (NFD), high-fat diet (HFD), or HFD + 2 g/kg genistein; the
      effects of dietary genistein on hyperlipidemia were investigated using
      traditional and (1)H NMR metabonomic approaches. At 6 weeks, compared with the
      hamsters in the NFD group, those in the HFD group had higher plasma and liver
      lipids (P < 0.05). Hyperlipidemia was alleviated in the genistein group, with
      lower plasma cholesterol (9.11 +/- 0.40 vs 12.4 +/- 0.37 mmol/L), triglyceride
      (8.07 +/- 1.08 vs 14.7 +/- 1.18 mmol/L), LDL cholesterol (2.69 +/- 0.20 vs 4.48
      +/- 0.27 mmol/L), malondialdehyde (7.77 +/- 1.64 vs 14.0 +/- 1.15 MUmol/L), and
      liver cholesterol (20.9 +/- 1.01 vs 29.9 +/- 2.76 MUmol/g) than those in the HFD
      group (P < 0.05). Expression of hepatic LDL receptor and estrogen receptors alpha
      and beta mRNA in the genistein group were significantly up-regulated, compared
      with those of the HFD group (P < 0.05). In the (1)H NMR metabonomic analysis,
      both the small and macromolecular plasma metabolite profiles differed among the
      three groups, and the metabolic profile of the genistein group was shifted toward
      that of the NFD group. These results extend our understanding of the beneficial
      effects of genistein on hyperlipidemia. 

PMID- 26311092
TI  - Current Trends in Management of Atlantoaxial Dislocation.
AB  - Atlantoaxial dislocation (AAD), often caused by trauma, tumors or congenital
      malformations, is a challenging disorder of the craniocervical junction. Because
      of its deep location and intricate anatomic structure, the craniocervical
      junction is always a difficult region for spine surgery. With recent developments
      in medical science, great progress has been made in the diagnosis and treatment
      of AAD such that more instructive clinical classifications and efficacious
      treatment strategies, various novel operation techniques including innovative
      posterior or transoral anterior reduction, and novel fixation instruments are now
      widely used in clinical practice for managing AAD. However, surgeons continue to
      face more special characteristics and difficulty in carrying out upper cervical
      surgery than they encounter in other regions of the spine. Consequently, this
      high risk surgery should only be performed by extremely skilled and experienced
      surgeons and only when stringent indications have been met. Therefore, the aim of
      this course is to assist surgeons who are dealing with AAD by providing
      comprehensive information about AAD, including related anatomy, classification,
      clinical manifestations and diagnosis, imaging examinations and surgical
      techniques, thus decreasing the occurrence of complications and improving the
      level of diagnosis and treatment. 

PMID- 26311093
TI  - Guideline for Diagnostic and Treatment of Osteonecrosis of the Femoral Head.
AB  - There is a new knowledge for clinical presentations and findings of imagine in
      patients with osteonecrosis of the femoral head (ONFH) in recent more than ten
      years. According to clinical data in Chinese huge patients with ONFH, the
      guideline for diagnosis and treatment of ONFH has been put forward by Chinese
      specialists. The newer contents of guideline include the definition for
      predisposing risk factors of ONFH, the new knowledge for clinical manifestations,
      the new interpretation for changes of imagine, important differential diagnosis.
      Based on the supplementary and revision for widely used staging and
      classification system, the new Chinese staging and classification system have
      been established. The advantages of Chinese staging and classification system
      accord with clinical and pathological features, it could be predicted the
      prognosis, and clinical applications are convenient. The guideline gives a brief
      account of principles for treatment selection and treatment methods for
      enhancement of diagnosis and treatment for ONFH. 

PMID- 26311095
TI  - Cortical Bone Trajectory for Lumbar Pedicle Screw Placement: A Review of
      Published Reports.
AB  - There have been a number of developments in screw design and implantation
      techniques over recent years, including proposal of an alternative trajectory for
      screw fixation aimed at increasing purchase of pedicle screws in higher density
      bone. Cortical bone trajectory (CBT) screw insertion follows a lateral path in
      the transverse plane and caudocephalad path in the sagittal plane. This technique
      has been advocated because it is reportedly less invasive, improves screw-bone
      purchase and reduces neurovascular injury; however, these claims have not been
      supported by robust clinical evidence. The available evidence was therefore
      reviewed to assess the relative merits of CBT and highlight areas for further
      research. To this end, a search of relevant published studies reporting
      biomechanical, morphometric or clinical outcomes after use of CBT screws in
      patients with spinal pathologies was performed via six electronic databases. 

PMID- 26311096
TI  - Role of Curcumin in Common Musculoskeletal Disorders: a Review of Current
      Laboratory, Translational, and Clinical Data.
AB  - The Indian spice turmeric, in which the active and dominant biomolecule is
      curcumin, has been demonstrated to have significant medicinal properties,
      including anti-inflammatory and anti-neoplastic effects. This promise is
      potentially very applicable to musculoskeletal disorders, which are common causes
      of physician visits worldwide. Research at the laboratory, translational and
      clinical levels that supports the use of curcumin for various musculoskeletal
      disorders, such as osteoarthritis, osteoporosis, musculocartilaginous disorders,
      and sarcoma is here in comprehensively summarized. Though more phase I-III trials
      are clearly needed, thus far the existing data show that curcumin can indeed
      potentially be useful in treatment of the hundreds of millions worldwide who are
      afflicted by these musculoskeletal disorders. 

PMID- 26311094
TI  - Clinical Guideline for Treatment of Symptomatic Thoracic Spinal Stenosis.
AB  - Thoracic spinal stenosis is a relatively common disorder causing paraplegia in
      the population of China. Until nowadays, the clinical management of thoracic
      spinal stenosis is still demanding and challenging with lots of questions
      remaining to be answered. A clinical guideline for the treatment of symptomatic
      thoracic spinal stenosis has been created by reaching the consensus of Chinese
      specialists using the best available evidence as a tool to aid practitioners
      involved with the care of this disease. In this guideline, many fundamental
      questions about thoracic spinal stenosis which were controversial have been
      explained clearly, including the definition of thoracic spinal stenosis, the
      standard procedure for diagnosing symptomatic thoracic spinal stenosis,
      indications for surgery, and so on. According to the consensus on the definition
      of thoracic spinal stenosis, the soft herniation of thoracic discs has been
      excluded from the pathological factors causing thoracic spinal stenosis. The
      procedure for diagnosing thoracic spinal stenosis has been quite mature, while
      the principles for selecting operative procedures remain to be improved. This
      guideline will be updated on a timely schedule and adhering to its
      recommendations should not be mandatory because it does not have the force of
      law. 

PMID- 26311097
TI  - Isthmus-guided Cortical Bone Trajectory Reduces Postoperative Increases in Serum
      Creatinine Phosphokinase Concentrations.
AB  - OBJECTIVE: This study aimed to determine whether an isthmus-guided cortical bone
      trajectory (CBT) technique provides better clinical outcomes than the original
      cortical bone trajectory CBT technique for screw fixation. METHODS: A consecutive
      series of 21 patients with lumbar spondylolisthesis who had undergone CBT screw
      fixation using the original technique from June 2012 to February 2013 and 33 who
      had undergone the isthmus-guided technique from March 2013 to August 2014 was
      retrospectively reviewed. The number of screws inserted, interbody fusion and
      screw misplacements, amount of blood loss, and creatinine phosphokinase (CPK)
      ratios (postoperative day 1 CPK/preoperative CPK) were reviewed to evaluate
      clinical outcomes and compared between the original and isthmus-guided CBT
      techniques. RESULTS: Postoperative serum CPK concentrations were significantly
      lower with the isthmus-guided than the original CBT technique (P < 0.05). There
      were no significant differences in age, blood loss, or number of screws,
      vertebral interbody fusions and patients with history of previous decompression
      surgery at the same level. There was a trend to higher incidence of screw
      misplacement with the original than the isthmus-guided CBT technique; this
      difference was not significant (P = 0.53). There were no major intraoperative
      complications. In all the CBT procedures performed in our institution, almost
      half (47%) the screw misplacements have occurred at the level of L5 , and most on
      the right side. CONCLUSIONS: Right-handed operators should take care inserting
      screws on the right side. From the viewpoint of screw misplacement, isthmus
      guided CBT provides superior or equivalent safety to the original CBT technique.

PMID- 26311098
TI  - Role of Intraoperative Disc Contrast Injection in Determining the Segment
      Responsible for Cervical Spinal Cord Injury without Radiographic Abnormalities.
AB  - OBJECTIVE: To determine the features of discs in spinal cord injury without
      radiographic abnormality (SCIWORA) by intraoperative disc contrast injection
      (IODCI) and to subsequently treat the responsible discs operatively. METHODS:
      From January 2007 to December 2011, 16 adult cases of cervical SCIWORA were
      enrolled in this study. The average preoperative Japanese Orthopaedic Association
      (JOA) score was 9.1 +/- 1.8. Although preoperative imaging showed no obvious
      fracture or dislocation, spinal cord compression was evident in all cases. High
      spinal cord signals on MRI T2WI and cervical disc degeneration were present in
      all cases and swollen soft tissue anterior to the cervical spine in nine cases.
      All patients underwent anterior cervical surgeries for spinal cord compression,
      IODCI being performed after exposure of suspicious discs. Patients with only one
      ruptured disc underwent anterior cervical discectomy and fusion; those with more
      complex injuries underwent anterior cervical corpectomy and fusion with fixation
      of the ruptured segment. JOA scores, X-rays and CT scans were checked at
      specified intervals over an average of 24.4 months. RESULTS: Of 32 discs
      suspected preoperatively of being injured, 19 were identified as ruptured by
      IODCI. Anterior annulus fibrosus rupture was proved in 11 patients whereas the
      anterior longitudinal ligament was intact in all. JOA scores at 2 weeks, 3 months
      and last follow-up postoperatively were 13.3 +/- 1.5, 14.5 +/- 1.6 and 15.1 +/-
      1.5 respectively. The recovery rates were 53.2%, 68.3% and 75.9%, respectively.
      CONCLUSION: IODCI helps to determine the segment responsible for cervical
      SCIWORA.

PMID- 26311099
TI  - Unilateral Hemilaminectomy for Intradural Lesions.
AB  - OBJECTIVE: Unilateral hemilaminectomy (UHIL), an alternative surgical approach to
      intradural lesions, involves a unilateral approach to meningeal opening that
      provides an adequate window for tumor extraction while leaving most of the
      vertebral structures intact. The techniques and results of a modified
      hemilaminectomy technique with spinal endoscopy is discussed and limited
      unilateral hemilaminectomy for intradural tumors (UHIT) evaluated prospectively.
      METHODS: Relevant clinical variables, operative reports, histological findings,
      pre- and post-operative imaging, and follow-up data for 11 consecutive patients
      (five males, six females; mean age 63.36 +/- 20.69 years) who underwent modified
      hemilaminectomy over a 3 year time period were analyzed. Contrast-enhanced MRI
      was used to demonstrate the side, size and location of the suspected tumor or
      intradural lesion and CT to evaluate the bone anatomy. Post-operative MRI and CT
      allowed evaluation of anatomy following resection. RESULTS: Lesions included
      meningiomas (n = 2), neuromas (n = 3), and metastases, cysts or gliomas (n = 6).
      Pre-operative indications in order of incidence included cord compression,
      claudication, lower back pain, radiculopathy, paraplegia, weakness, incontinence,
      and generalized neuro-deterioration. There were no major complications, and no
      spinal deformity or instability at final follow up (mean, 13 months; range, 3-36
      months). CONCLUSION: Our data suggest that there is a place for the UHIT
      approach. This minimally invasive approach is useful for resecting all intradural
      tumors. UHIL is a useful minimally invasive technique for resecting intradural
      spinal tumors with maximal preservation of musculoligamentous attachments and
      posterior bony elements and should be considered an improvement on currently
      employed techniques.

PMID- 26311100
TI  - Intra-articular Adjuvant Analgesics following Knee Arthroscopy: Comparison
      between Single and Double Dose Dexmedetomidine and Ropivacaine A Multicenter
      Prospective Double-blind Trial.
AB  - OBJECTIVE: Knee arthroscopy is a commonly performed orthopedic procedure. Post
      operatively, adequate pain relief reduces the surgical stress response and
      patient's morbidity and facilitates rehabilitation. The analgesic effect of
      dexmedetomidine (2 MUg/kg body weight) as an adjunct to ropivacaine in knee
      arthroscopic knee procedures was studied to determine whether this would achieve
      longer post-operative analgesia and whether the study dosage of dexmedetomidine
      was safe and free of adverse effects. PATIENTS AND METHODS: In a multicenter
      prospective double blind trial of sixty patients undergoing knee arthroscopic
      procedures, patients were randomly assigned to three groups: Group R, receiving
      intra-articular ropivacaine (20 mL); Group D1 (18 mL ropivacaine, dexmedetomidine
      1 MUg/kg body weight); and Group D2 (18 mL ropivacaine, dexmedetomidine 2
      MUg/kg). RESULTS: Group D2 had significantly lower pain scores for the first 12
      postoperative hours than Group D1 and Group R. Time to first analgesic
      requirement was longest in Group D2 (757.30 +/- 207.68 min), followed by Group D1
      (433.2 +/- 54.3 min) and Group R (311.80 +/- 61.56 min); these differences were
      significant (P < 0.05). Total analgesic requirement was significantly lower in
      Group D2 (82.50 +/- 48.05 mg; P < 0.05). Intensity of pain was significantly less
      in Group D2 in the third (P < 0.01) and sixth hours (P < 0.05). CONCLUSION: Intra
      articular dexmedetomidine (2 MUg/kg) has superior analgesic efficacy, delayed the
      first postoperative requirement for analgesia and decreasing the need for
      postoperative analgesics with no major adverse effects.

PMID- 26311101
TI  - Fixation of Metacarpal Shaft Fractures: Biomechanical Comparison of
      Intramedullary Nail Crossed K-Wires and Plate-Screw Constructs.
AB  - OBJECTIVES: Metacarpal (MC) fractures are very common, accounting for 18% of all
      fractures distal to the elbow. Many MC fractures can be treated non-operatively;
      however, some are treated most effectively with surgical stabilization, for which
      there are multiple methods. It was postulated that plates would have a
      significantly higher (P < 0.05) load to failure than crossed K(XK)-wires and that
      intramedullary metacarpal nails (IMNs) and XK-wires would have equivalent load to
      failure. METHODS: Mid-diaphyseal transverse fractures were created in 36
      synthetic metacarpals and stabilized using nails, XK-wires or non-locking plates.
      Three-point bending was performed with continuous recording of load and
      displacement. Statistical analysis was performed using single factor ANOVA and
      Scheffe's test. Statistical significance was defined as P < 0.05. RESULTS:
      Biomechanical testing revealed significant differences between groups in load-to
      failure. Average load to failure was significantly greater in the plate (1669 +/-
      322 N) than the XK-wire (146 +/- 56 N) or IMN (110 +/- 43 N) groups. The loads to
      failure of the K-wires and nails were equivalent. Plates were 11 and 15 times
      stronger in three-point bending than the K-wires and nails, respectively. There
      was no statistically significant difference between strengths of the K-wires and
      nails. CONCLUSIONS: Although plates are the most stable means of fixation of
      midshaft metacarpal fractures, if minimally-invasive techniques are indicated,
      intramedullary nails may provide equivalent stability as commonly-used XK-wires.
      Although some studies have shown favorable clinical outcomes with IMNs,
      additional clinical correlation of these biomechanical results to fracture
      healing and outcomes is needed.

PMID- 26311102
TI  - Effects of Cemented Hip Stem Pre-heating on Stem Push-out Strength.
AB  - OBJECTIVE: To determine the effect on ultimate push-out load and cement-stem
      surface shear strength of thermally manipulating the cobalt-chromium-molybdenum
      (CoCrMo) alloy stems of bone cement-stem constructs. METHODS: Satin-finished
      CoCrMo alloy stems were allocated to the following three groups with the
      predetermined temperatures: T24, ambient (24  degrees C); T37, body (37  degrees
      C); and T44, pre-heated stem (>44  degrees C). They were then inserted into hand
      mixed high viscosity bone cement. Ultimate push-out load to failure was assessed
      with a servo hydraulic testing machine and the surface shear strength calculated.
      Data were compared among groups using the Kruskal-Wallis with Dunn's test. A P
      value of less than 0.05 was considered statistically significant. RESULTS:
      According to Kruskal-Wallis analysis, ultimate push-out load and surface shear
      strength differed significantly between the groups (P = 0.001). The T37 and T44
      groups had higher ultimate push-out loads and surface shear strengths than the
      T24 group (P = 0.04 and 0.001, respectively). However, there was no statistically
      significant difference in these two variables between the T37 and T44 groups (P =
      0.08). CONCLUSIONS: Pre-heating CoCrMo alloy stems enhance the ultimate push-out
      load and surface shear strength in vitro. The suggested temperature is 37 
      degrees C. This technique is recommended for hip arthroplasty procedures.

PMID- 26311103
TI  - Reconstruction of Segmental Stability of Goat Cervical Spine with Poly (D, L
      lactic acid) Cage.
AB  - OBJECTIVES: To compare the characteristics of inter body fusion after using an
      established poly (D, L-lactic acid) (PDLLA) cage, a titanium cage or autologous
      tricortical iliac crest graft in a goat cervical spine model in vivo. METHODS:
      Twenty-four goats were assigned to three groups: PDLLA cage group (n = 8),
      titanium alloy cage group (n = 8) and autologous iliac bone group (n = 8), and
      underwent C3-4 discectomy and fusion with the allocated procedure. Radiography
      was performed pre- and post-operatively and after 1, 2, 4, 8 and 12 weeks and
      disc space height (DSH), intervertebral angle (IVA), and lordosis angle (LA)
      measured at these time points. After 12 weeks, the goats were killed and fusion
      sites removed. Biomechanical testing was performed in flexion, extension, axial
      rotation, and lateral bending to determine the stiffness and range of motion
      (ROM). All specimens were also assessed histomorphologically. RESULTS: The IVA of
      PDLLA cage four weeks postoperatively and DSH eight and twelve weeks
      postoperatively were significantly greater than that of autologous iliac bone
      graft (P < 0.05). The LA values did not differ significantly between groups. The
      stiffness of both types of cages for axial rotation and lateral bending, and ROM
      for every movement, were significantly greater than that of the autologous iliac
      bone graft group (P < 0.05). PDLLA and titanium cages did not differ
      significantly (P > 0.05). Radiographic and histomorphological assessment showed
      better fusion in the cage than the autologous bone groups. CONCLUSION: The PDLLA
      cage can provide good intervertebral distract ability and enough biomechanical
      stability for cervical fusion.

PMID- 26311104
TI  - Effects of Ezrin and Heat Shock Protein 70 on Apoptosis and Proliferation of
      Human Osteosarcoma Cells.
AB  - OBJECTIVE: To investigate the influence of knocking down ezrin expression in
      combination with heat shock protein (HSP)-induced immune killing on the apoptosis
      and proliferation of mouse osteosarcoma cells. METHODS: The HSP70 and ezrin-shRNA
      DNA fragments cloned into the expression vector pGFP-V-RS and the expression
      vectors pGFP-V-RS-shRNA and pGFP-V-RS-shRNA-HSP70 constructed and transfected
      into MG63 cell line, where their status was observed by fluorescent microscopy.
      Expression of ezrin and HSP70 was determined by RT-PCR and western blot. Changes
      in cell apoptosis and proliferation were assessed by flow cytometry and MTS and
      changes in expression of apoptosis and cell cycle-related proteins by western
      blot. Specific cytotoxic T lymphocytes (CTLs) were induced by HSP70 and its
      lethal effect on target MG63 tumor cells analyzed by MTS assay. RESULTS: The
      specific vector simultaneously downregulated ezrin and upregulated HSP70.
      Compared with ezrin knockdown alone, simultaneous HSP70 overexpression partially
      recovered the promoted cellular apoptosis and proliferation suppression by
      induced by ezrin knockdown; however, the apoptosis rate of MG63 cells was
      significantly greater than that of a negative control. In addition, ezrin-shRNA
      and ezrin-shRNA/HSP70 promoted expression of Bax. However, expression of these
      agents reduces Bcl-2 and Cyclin D1. The cytotoxic effects of CTLs on target MG63
      tumor cells were significantly greater in the CTL + IL-2 + HSP70 group than the
      CTL + IL-2 group. CONCLUSIONS: Simultaneously knocking down ezrin and
      overexpressing HSP70 promotes apoptosis and inhibits proliferation of
      osteosarcoma cells and HSP70 induces CTL, enhancing the lethal effect on tumor
      cells.

PMID- 26311105
TI  - Bilateral Vertebral Artery Injury in a Patient with Upper Cervical Spine
      Fractures Leading to Fatal Vertebrobasilar Infarction: A Case Report.

PMID- 26311106
TI  - Total Femur Replacement for Treatment of Chondrosarcoma Involving the Entire
      Femur.

PMID- 26311107
TI  - Treatment of Ankle Fractures with Open Reduction Internal Fixation via Improved
      Posterolateral Incision.

PMID- 26311108
TI  - Developed and evaluated a multiplex mRNA profiling system for body fluid
      identification in Chinese Han population.
AB  - In forensic casework, identification the cellular origin from a biological sample
      is crucial to the case investigation and reconstruction in crime scene. DNA/RNA
      co-extraction for STR typing and human body fluids identification has been
      proposed as an efficient and comprehensive assay for forensic analysis. Several
      cell-specific messenger RNA (mRNA) markers for identification of the body fluids
      have been proposed by previous studies. In this study, a novel multiplex mRNA
      profiling system included 19 markers was developed and performed by reverse
      transcription endpoint polymerase chain reaction (RT-PCR). The multiplex combined
      3 housekeeping gene markers and 16 cell-specific markers that have been used to
      identify five types of human body fluids: peripheral blood, semen, saliva,
      vaginal secretions and menstrual blood. The specificity, sensitivity, stability
      and detectability of the mixture were explored in our study. Majority of the cell
      specific mRNA markers showed high specificity, although cross-reactivity was
      observed sporadically. Specific profiling for per body fluid was obtained.
      Moreover, the interpretation guidelines for inference of body fluid types were
      performed according to the A. Lindenbergh et al. The scoring guidelines can be
      applied to any RNA multiplex, which was based on six different scoring categories
      (observed, observed and fits, sporadically observed and fits, not observed,
      sporadically observed, not reliable, and non-specific due to high input). The
      simultaneous extraction of DNA showed positive full or partial profiling results
      of all samples. It demonstrated that the approach of combined STR-profiling and
      RNA profiling was suitable and reliable to detect the donor and origin of human
      body fluids in Chinese Han population. 

PMID- 26311109
TI  - Nonradiating anapole modes in dielectric nanoparticles.
AB  - Nonradiating current configurations attract attention of physicists for many
      years as possible models of stable atoms. One intriguing example of such a
      nonradiating source is known as 'anapole'. An anapole mode can be viewed as a
      composition of electric and toroidal dipole moments, resulting in destructive
      interference of the radiation fields due to similarity of their far-field
      scattering patterns. Here we demonstrate experimentally that dielectric
      nanoparticles can exhibit a radiationless anapole mode in visible. We achieve the
      spectral overlap of the toroidal and electric dipole modes through a geometry
      tuning, and observe a highly pronounced dip in the far-field scattering
      accompanied by the specific near-field distribution associated with the anapole
      mode. The anapole physics provides a unique playground for the study of
      electromagnetic properties of nontrivial excitations of complex fields,
      reciprocity violation and Aharonov-Bohm like phenomena at optical frequencies. 

PMID- 26311110
TI  - Effects of combined aerobic and resistance training on the glycolipid metabolism
      and inflammation levels in type 2 diabetes mellitus.
AB  - [Purpose] To investigate the effects of combined aerobic and resistance training
      on glycolipid metabolism and inflammation levels in type 2 diabetes mellitus
      patients. [Subjects and Methods] Forty-two diabetes patients were randomized to
      the conventional therapy group (n = 20) or intensive therapy group (n = 22). The
      control group contained 20 healthy people. The conventional therapy group
      received routine drug therapy and diet control, while the intensive therapy group
      additionally underwent combined aerobic and resistance training for 12 weeks. The
      oral glucose tolerance test and cardiopulmonary exercise testing were performed.
      Toll-like receptor 4 and NF-kappaBp65 protein and mRNA expressions were
      determined by qPCR and western blotting. ELISA was used to determine the
      expression levels of interleukin-18, interleukin-33, pentraxin-related protein 3,
      and human cartilage glycoprotein 39. [Results] After exercise training, the
      intensive therapy group had significantly lower postprandial blood glucose,
      postprandial insulin, and glycated hemoglobin level and insulin resistance index
      than the conventional therapy group. The intensive therapy group had
      significantly lower toll-like receptor 4 and NF-kappaBp65 protein and mRNA
      expressions, and serum interleukin-18 levels but significantly higher serum
      interleukin-33 levels. [Conclusion] Combined aerobic and resistance training can
      improve glycolipid metabolism and reduce low-grade inflammation in patients with
      diabetes mellitus patients. 

PMID- 26311111
TI  - Percutaneous Radiofrequency Lesion of the Superior Cervical Sympathetic Ganglion
      in Patients with Tinnitus.
AB  - OBJECTIVE: The aim of this study was to determine the efficacy of radiofrequency
      lesioning of the superior cervical sympathetic ganglion for patients with
      tinnitus. STUDY DESIGN: This is a retrospective long-term clinical review of
      patients with tinnitus treated with a blockade of the superior cervical
      sympathetic ganglion. SETTING: The human subjects were 366 consecutive patients
      who came to the DC Klinieken in Almere and Amsterdam from January 2010 to January
      2014 for consultations on their tinnitus that persisted for 1 month or longer.
      SUBJECTS AND METHODS: Data were recorded from patients whose charts were reviewed
      retrospectively to identify the patients who were treated with a blockade of the
      superior cervical sympathetic ganglion for tinnitus. An independent observer
      conducted a long-term follow-up assessment of the therapy by telephone interview.
      RESULTS: Relief of tinnitus at 7-week follow-up was achieved in 64% of the
      patients treated with a radiofrequency lesion of the superior cervical
      sympathetic ganglion after a positive test blockade of this structure. Two years
      after the treatment, the maintenance of a tinnitus relief occurred in almost 40%
      of the patients with a follow-up period of two years or longer. CONCLUSIONS: A
      radiofrequency lesion of the superior cervical sympathetic ganglion may be a
      useful alternative for patients with tinnitus not responding to conventional
      therapy.

PMID- 26311112
TI  - Renal depletion of myo-inositol is associated with its increased degradation in
      animal models of metabolic disease.
AB  - Renal depletion of myo-inositol (MI) is associated with the pathogenesis of
      diabetic nephropathy in animal models, but the underlying mechanisms involved are
      unclear. We hypothesized that MI depletion was due to changes in inositol
      metabolism and therefore examined the expression of genes regulating de novo
      biosynthesis, reabsorption, and catabolism of MI. We also extended the analyses
      from diabetes mellitus to animal models of dietary-induced obesity and
      hypertension. We found that renal MI depletion was pervasive across these three
      distinct disease states in the relative order: hypertension (-51%)>diabetes
      mellitus (-35%)>dietary-induced obesity (-19%). In 4-wk diabetic kidneys and in
      kidneys derived from insulin-resistant and hypertensive rats, MI depletion was
      correlated with activity of the MI-degrading enzyme myo-inositol oxygenase
      (MIOX). By contrast, there was decreased MIOX expression in 8-wk diabetic
      kidneys. Immunohistochemistry localized the MI-degrading pathway comprising MIOX
      and the glucuronate-xylulose (GX) pathway to the proximal tubules within the
      renal cortex. These findings indicate that MI depletion could reflect increased
      catabolism through MIOX and the GX pathway and implicate a common pathological
      mechanism contributing to renal oxidative stress in metabolic disease.

PMID- 26311113
TI  - A mouse model of Townes-Brocks syndrome expressing a truncated mutant Sall1
      protein is protected from acute kidney injury.
AB  - It has been postulated that developmental pathways are reutilized during repair
      and regeneration after injury, but functional analysis of many genes required for
      kidney formation has not been performed in the adult organ. Mutations in SALL1
      cause Townes-Brocks syndrome (TBS) and nonsyndromic congenital anomalies of the
      kidney and urinary tract, both of which lead to childhood kidney failure. Sall1
      is a transcriptional regulator that is expressed in renal progenitor cells and
      developing nephrons in the embryo. However, its role in the adult kidney has not
      been investigated. Using a mouse model of TBS (Sall1TBS), we investigated the
      role of Sall1 in response to acute kidney injury. Our studies revealed that Sall1
      is expressed in terminally differentiated renal epithelia, including the S3
      segment of the proximal tubule, in the mature kidney. Sall1TBS mice exhibited
      significant protection from ischemia-reperfusion injury and aristolochic acid
      induced nephrotoxicity. This protection from acute injury is seen despite the
      presence of slowly progressive chronic kidney disease in Sall1TBS mice. Mice
      containing null alleles of Sall1 are not protected from acute kidney injury,
      indicating that expression of a truncated mutant protein from the Sall1TBS
      allele, while causative of congenital anomalies, protects the adult kidney from
      injury. Our studies further revealed that basal levels of the preconditioning
      factor heme oxygenase-1 are elevated in Sall1TBS kidneys, suggesting a mechanism
      for the relative resistance to injury in this model. Together, these studies
      establish a functional role for Sall1 in the response of the adult kidney to
      acute injury.

PMID- 26311115
TI  - The fibroblast growth factor receptor mediates the increased FGF23 expression in
      acute and chronic uremia.
AB  - Serum FGF23 is markedly elevated in chronic kidney disease and has been
      associated with poor long-term outcomes. FGF23 expression is increased by
      activation of the FGF receptor 1 (FGFR1) in rats with normal renal function and
      in vitro in bone-derived osteoblast-like cells. We studied the regulation of
      FGF23 by FGFR1 in vivo in acute and chronic uremia in mice and rats. Folic acid
      induced acute kidney injury increased calvaria FGF23 mRNA and serum FGF23 and
      parathyroid hormone (PTH) levels at 6 h. The FGFR1 receptor inhibitor PD173074
      prevented the folic acid-induced increase in both FGF23 mRNA and serum levels but
      had no effect on serum PTH levels. A more prolonged uremia due to an adenine high
      phosphorus diet for 14 days resulted in high levels of FGF23 mRNA and serum FGF23
      and PTH. PD173074 decreased serum FGF23 and mRNA levels with no effect on PTH in
      the adenine high phosphorus-induced uremic rats. Therefore, a derangement in
      FGF23 regulation starts early in the course of acute kidney injury, is in part
      independent of the increase in serum PTH, and involves activation of FGFR1. It is
      possible that FGFR1 in the osteocyte is activated by locally produced canonical
      FGFs, which are increased in uremia. This is the first demonstration that
      activation of FGFR1 is essential for the high levels of FGF23 in acute and
      chronic experimental uremia. 

PMID- 26311116
TI  - The sunshine act and medical publications: Guidance from professional medical
      associations.
AB  - OBJECTIVE: To review guidance from professional medical associations to
      physicians on the Sunshine Act, with a focus on industry support for medical
      publications. METHODS: Using 'Sunshine Act' as a search term, we searched PubMed
      (dates February 2013 to November 2014) and the 'grey literature' using Google and
      Google Scholar. Online information was extracted from websites of pre-identified
      professional medical associations. RESULTS: Some professional medical
      associations have published peer-reviewed recommendations, position statements or
      general advice on their websites and in journals around the Sunshine Act.
      Associations also provided broad online educational resources for physicians.
      There was universal agreement between peer-reviewed publications, including
      guidelines, for the need for full transparency and disclosure of industry
      support. Surveys by some professional associations showed variance in opinion on
      the forecasted impact of the Sunshine Act on physician-industry relationships.
      There was scarce information specifically related to reporting requirements for
      industry-supported medical publications. CONCLUSIONS: There is a shortage of
      information for physicians from professional associations regarding the Sunshine
      Act and support for medical publications. Due to the lack of clear guidance
      regarding support for publications, there are presently varying interpretations
      of the Sunshine Act. The literature debates the potential impact of the Sunshine
      Act and expresses some concerns that physician-enabled innovation in drug
      development may be hindered.

PMID- 26311114
TI  - Molecular mechanisms of ischemic preconditioning in the kidney.
AB  - More effective therapeutic strategies for the prevention and treatment of acute
      kidney injury (AKI) are needed to improve the high morbidity and mortality
      associated with this frequently encountered clinical condition. Ischemic and/or
      hypoxic preconditioning attenuates susceptibility to ischemic injury, which
      results from both oxygen and nutrient deprivation and accounts for most cases of
      AKI. While multiple signaling pathways have been implicated in renoprotection,
      this review will focus on oxygen-regulated cellular and molecular responses that
      enhance the kidney's tolerance to ischemia and promote renal repair. Central
      mediators of cellular adaptation to hypoxia are hypoxia-inducible factors (HIFs).
      HIFs play a crucial role in ischemic/hypoxic preconditioning through the
      reprogramming of cellular energy metabolism, and by coordinating adenosine and
      nitric oxide signaling with antiapoptotic, oxidative stress, and immune
      responses. The therapeutic potential of HIF activation for the treatment and
      prevention of ischemic injuries will be critically examined in this review. 

PMID- 26311117
TI  - Overexpression Of Hepatocyte Nuclear Factor-1beta Predicting Poor Prognosis Is
      Associated With Biliary Phenotype In Patients With Hepatocellular Carcinoma.
AB  - Hepatocyte nuclear factor-1beta (HNF-1B) is involved in the hepatobiliary
      specification of hepatoblasts to cholangiocytes during liver development, and is
      strongly expressed throughout adult biliary epithelium. The aim of this study was
      to examine the expression of HNF-1B in different pathologic subtypes of primary
      liver cancer, including hepatocellular carcinoma (HCC) and cholangiocarcinoma
      (ICC), and the relationship between HNF-1B expression, clinicopathological
      features and prognosis. We retrospectively investigated 2 cohorts of patients,
      including 183 HCCs and 69 ICCs. The expression of HNF-1B was examined by
      immunohistochemistry. We found that HNF-1B expression was associated with
      pathological subtype of primary tumor, and HNF-1B expression in HCC tissue may be
      associated with the change of phenotype on recurrence. The HNF-1B expression was
      positively correlated with biliary/HPC (hepatic progenitor cell) markers
      expression. Further, multivariable analysis showed that HNF-1B expression was an
      independent prognostic factor for both overall survival and disease-free survival
      of HCC patients. However, no correlation between HNF-1B expression and survival
      was found in ICC patients. In summary, HCC with high HNF-1B expression displayed
      biliary phenotype and tended to show poorer prognosis. HNF-1B-positive malignant
      cells could be bipotential cells and give rise to both hepatocytic and
      cholangiocytic lineages during tumorigenesis. 

PMID- 26311118
TI  - Incidence and risk factors for recurrent spontaneous preterm birth: A
      retrospective cohort study in Japan.
AB  - AIM: The aim of this study was to assess the incidence and risk factors for
      recurrent spontaneous preterm birth (PTB) in Japan. MATERIAL AND METHODS: A
      retrospective cohort study was conducted at five tertiary perinatal centers in
      Osaka, Japan from 2008 through 2012. Perinatal data were collected from medical
      records of women with a singleton gestation and a previous spontaneous PTB.
      Exclusion criteria were first-trimester spontaneous abortion, first antenatal
      visit beyond 14 weeks of gestation, and previous PTB with medical indications,
      placenta previa, abruptio placenta, multiple pregnancy, fetal anomaly, and
      antepartum fetal demise. The associations between recurrent spontaneous PTB and
      perinatal factors were evaluated by logistic regression analysis. RESULTS: Of 547
      women with a previous spontaneous PTB, 89 (16.3%) suffered a recurrent
      spontaneous PTB. The risk factors for recurrence included multiple previous
      spontaneous PTB (adjusted odds ratio [aOR]: 2.26; 95% confidence interval [CI]:
      1.19-4.30; P = 0.013), no previous term birth (aOR: 2.08; 95%CI: 1.24-3.49; P =
      0.005), and interpregnancy interval < 12 months (aOR: 2.13; 95%CI: 1.17-3.85; P =
      0.013). CONCLUSION: Approximately one in six women with a previous spontaneous
      PTB suffered a recurrent spontaneous PTB. Multiple previous spontaneous PTB, no
      previous term birth, and short interpregnancy interval were independent risk
      factors for recurrence.

PMID- 26311119
TI  - Is it appropriate to use fixed assay cut-offs for estimating seroprevalence?
AB  - Population seroprevalence can be estimated from serosurveys by classifying
      quantitative measurements into positives (past infection/vaccinated) or negatives
      (susceptible) according to a fixed assay cut-off. The choice of assay cut-offs
      has a direct impact on seroprevalence estimates. A time-resolved fluorescence
      immunoassay (TRFIA) was used to test exposure to human parvovirus 4 (HP4).
      Seroprevalence estimates were obtained after applying the diagnostic assay cut
      off under different scenarios using simulations. Alternative methods for
      estimating assay cut-offs were proposed based on mixture modelling with component
      distributions for the past infection/vaccinated and susceptible populations.
      Seroprevalence estimates were compared to those obtained directly from the data
      using mixture models. Simulation results showed that when there was good
      distinction between the underlying populations all methods gave seroprevalence
      estimates close to the true one. For high overlap between the underlying
      components, the diagnostic assay cut-off generally gave the most biased
      estimates. However, the mixture model methods also gave biased estimates which
      were a result of poor model fit. In conclusion, fixed cut-offs often produce
      biased estimates but they also have advantages compared to other methods such as
      mixture models. The bias can be reduced by using assay cut-offs estimated
      specifically for seroprevalence studies. 

PMID- 26311120
TI  - The presentation of lymph nodes in Hashimoto's thyroiditis on ultrasound.
AB  - BACKGROUND: Comprehensive neck ultrasound (US) examination has become an
      essential component of preoperative workup for patients with thyroid cancer.
      Regional cervical lymph nodes may be involved in cases of Hashimoto's thyroiditis
      (HT). This study seeks to examine the sonographic pattern of lymph nodes in
      patients with HT. METHODS: This is a retrospective study looking at patients with
      confirmed diagnoses of HT on final surgical pathology who underwent preoperative
      comprehensive neck US. We compared preoperative ultrasound for patients with HT
      to euthyroid patients with goiter. Data collected included number, size and
      ultrasonographic features of cervical lymph nodes. RESULTS: We included a total
      of 417 patients: 202 patients with HT in the study group, and 215 patients with
      goiter and euthyroid status in the control group. Patients with HT had a higher
      number of total cervical lymph nodes than the control group (2.00+/-2.35 vs.
      0.76+/-1.36 mm; P<0.0001), most notably in cervical levels III and IV (P<0.05 for
      both). CONCLUSIONS: HT seems to be associated with an ultrasonographic pattern of
      increased number of enlarged cervical lymph nodes, particularly in levels III,
      and IV.

PMID- 26311121
TI  - Heterogeneity of (18)F-FDG PET combined with expression of EGFR may improve the
      prognostic stratification of advanced oropharyngeal carcinoma.
AB  - The Ang's risk profile (based on p16, smoking and cancer stage) is a well-known
      prognostic factor in oropharyngeal squamous cell carcinoma (OPSCC). Whether
      heterogeneity in (18)F-fluorodeoxyglucose (FDG) positron emission tomographic
      (PET) images and epidermal growth factor receptor (EGFR) expression could provide
      additional information on clinical outcomes in advanced-stage OPSCC was
      investigated. Patients with stage III-IV OPSCC who completed primary therapy were
      eligible. Zone-size nonuniformity (ZSNU) extracted from pretreatment FDG PET
      scans was used as an index of image heterogeneity. EGFR and p16 expression were
      examined by immunohistochemistry. Disease-specific survival (DSS) and overall
      survival (OS) served as outcome measures. Kaplan-Meier estimates and Cox
      proportional hazards regression models were used for survival analysis. A
      bootstrap resampling technique was applied to investigate the stability of
      outcomes. Finally, a recursive partitioning analysis (RPA)-based model was
      constructed. A total of 113 patients were included, of which 28 were p16
      positive. Multivariate analysis identified the Ang's profile, EGFR and ZSNU as
      independent predictors of both DSS and OS. Using RPA, the three risk factors were
      used to devise a prognostic scoring system that successfully predicted DSS in
      both p16-positive and -negative cases. The c-statistic of the prognostic index
      for DSS was 0.81, a value which was significantly superior to both AJCC stage
      (0.60) and the Ang's risk profile (0.68). In patients showing an Ang's high-risk
      profile (N = 77), the use of our scoring system clearly identified three distinct
      prognostic subgroups. It was concluded that a novel index may improve the
      prognostic stratification of patients with advanced-stage OPSCC.

PMID- 26311123
TI  - Delayed proximal middle cerebral artery thrombosis after middle cranial base
      meningioma resection: a lesson to learn.

PMID- 26311122
TI  - Sleep Disturbances in Patients With Advanced Cancer in Different Palliative Care
      Settings.
AB  - CONTEXT: Information regarding sleep disturbances in the population with advanced
      cancer is meager. OBJECTIVES: To assess the prevalence of sleep disturbances and
      possible correlations with associated factors in a large number of patients with
      advanced cancer admitted to different palliative care settings. METHODS: This was
      an observational study performed in different settings of palliative care. A
      consecutive sample of patients with advanced cancer was prospectively assessed
      for a period of six months. Epidemiological and clinical data, treatments
      received in the last month, Karnofsky status, Edmonton Symptom Assessment System
      scores, and concomitant medical treatment were recorded. Patients were
      administered the Athens Insomnia Scale and the Hospital Anxiety and Depression
      Scale (HADS). RESULTS: A total of 820 patients were surveyed. Mean age was 69.7
      years (SD 12.7), and 429 patients were males. Consistent sleep disturbances
      (moderate to maximum) were found in 60.8% of patients. Aged patients were less
      likely to have sleep disturbances, whereas a poor Karnofsky level was
      significantly associated with sleep problems. Breast, gastrointestinal, head and
      neck, lung, and prostate cancers were associated with sleep problems. Patients
      who had a secondary school or undergraduate education had less sleep
      disturbances. Hormone therapy and use of opioids and corticosteroids were
      positively associated with sleep disturbances, and there was a positive
      correlation of HADS-Anxiety and HADS-Depression scores with sleep disturbances.
      CONCLUSION: More than 60% of palliative care patients have relevant sleep
      disturbances. Several factors associated with sleep disorders have been
      identified and should prompt physicians to make a careful examination and
      subsequent treatment of these disturbances.

PMID- 26311124
TI  - Ordinary stoichiometry of extraordinary microorganisms.
AB  - All life on Earth seems to be made of the same chemical elements in relatively
      conserved proportions (stoichiometry). Whether this stoichiometry is conserved in
      settings that differ radically in physicochemical conditions (extreme
      environments) from those commonly encountered elsewhere on the planet provides
      insight into possible stoichiometries for putative life beyond Earth. Here, we
      report measurements of elemental stoichiometry for extremophile microbes from hot
      springs of Yellowstone National Park (YNP). Phototrophic and chemotrophic
      microbes were collected in locations spanning large ranges of temperature (24 
      degrees C to boiling), pH (1.6-9.6), redox (0.1-7.2 mg L(-1) dissolved oxygen),
      and nutrient concentrations (0.01-0.25 mg L(-1) NO2-, 0.7-12.9 mg L(-1) NO3-,
      0.01-42 mg L(-1) NH4 (+), 0.003-1.1 mg L(-1) P mostly as phosphate). Despite
      these extreme conditions, the microbial cells sampled had a major and trace
      element stoichiometry within the ranges commonly encountered for microbes living
      in the more moderate environments of lakes and surface oceans. The cells did have
      somewhat high C:P and N:P ratios that are consistent with phosphorus (P)
      limitation. Furthermore, chemotrophs and phototrophs had similar compositions
      with the exception of Mo content, which was enriched in cells derived from
      chemotrophic sites. Thus, despite the extraordinary physicochemical and
      biological diversity of YNP environments, life in these settings, in a
      stoichiometric sense, remains much the same as we know it elsewhere.

PMID- 26311125
TI  - Copper nanoparticles/compounds impact agronomic and physiological parameters in
      cilantro (Coriandrum sativum).
AB  - The environmental impacts of Cu-based nanoparticles (NPs) are not well
      understood. In this study, cilantro (Coriandrum sativum) was germinated and grown
      in commercial potting mix soil amended with Cu(OH)2 (Kocide and CuPRO), nano
      copper (nCu), micro-copper (MUCu), nano-copper oxide (nCuO), micro-copper oxide
      (MUCuO) and ionic Cu (CuCl2) at either 20 or 80 mg Cu per kg. In addition to seed
      germination and plant elongation, relative chlorophyll content and micro and
      macroelement concentrations were determined. At both concentrations, only nCuO,
      MUCuO, and ionic Cu, showed statistically significant reductions in germination.
      Although compared with control, the relative germination was reduced by ~50% with
      nCuO at both concentrations, and by ~40% with MUCuO, also at both concentrations,
      the difference among compounds was not statistically significant. Exposure to
      MUCuO at both concentrations and nCu at 80 mg kg(-1) significantly reduced (p<=
      0.05) shoot elongation by 11% and 12.4%, respectively, compared with control.
      Only MUCuO at 20 mg kg(-1) significantly reduced (26%) the relative chlorophyll
      content, compared with control. None of the treatments increased root Cu, but all
      of them, except MUCuO at 20 mg kg(-1), significantly increased shoot Cu (p<=
      0.05). Micro and macro elements B, Zn, Mn, Ca, Mg, P, and S were significantly
      reduced in shoots (p<= 0.05). Similar results were observed in roots. These
      results showed that Cu-based NPs/compounds depress nutrient element accumulation
      in cilantro, which could impact human nutrition. 

PMID- 26311126
TI  - Characterization Through Multilocus Sequence Analysis of Borrelia turdi Isolates
      from Portugal.
AB  - Borrelia turdi is a spirochete from the Borrelia burgdorferi complex, first
      reported in Japan, that has been increasingly detected in Europe. This
      genospecies is mostly associated with avian hosts and their ornithophilic ticks
      such as Ixodes frontalis. In this study, we isolated B. turdi from five I.
      frontalis feeding on Turdus merula, Turdus philomelos, Parus major and
      Troglodytes troglodytes, and one Ixodes ricinus feeding on a T. merula in
      Portugal. These isolates were genetically characterised according to their 5S-23S
      rRNA intergenic spacer, 16S rRNA and through typing of seven housekeeping genes
      (multilocus sequence typing). Multilocus sequence analyses revealed that the
      strains isolated in our study, although belonging to B. turdi genospecies, are
      not identical to the B. turdi reference strain Ya501. Instead, our strains are
      separated into a clear defined group, suggesting that the European samples
      diverged genetically from the strain originally detected in Japan. Population
      analysis of 5S-23S rRNA sequences can further resolve subpopulations within B.
      turdi, but more samples from a large geographical scale and host range would be
      needed to assess potential phylogeographical patterns within this genospecies.

PMID- 26311127
TI  - Structure of Manila Clam (Ruditapes philippinarum) Microbiota at the Organ Scale
      in Contrasting Sets of Individuals.
AB  - Marine invertebrate microbiota has a key function in host physiology and health.
      To date, knowledge about bivalve microbiota is poorly documented except public
      health concerns. This study used a molecular approach to characterize the
      microbiota associated with the bivalve Manila clam (Ruditapes philippinarum) by
      determining (1) the difference among organs either or not under the influence of
      host habitat, (2) small-scale variability of microbiota, and (3) the experimental
      response of the Manila clam microbiota submitted to different lateral
      transmissions. These questions were investigated by sampling two groups of
      individuals living in contrasting habitats and carrying out a transplant
      experiment. Manila clam microbiota (i.e., bacterial community structure) was
      determined at organ-scale (gills, gut, and a pool of remaining tissues) by
      capillary electrophoresis DNA fingerprinting (CE fingerprinting). The Manila clam
      microbiota structure differed among organs indicating a selection of Manila clam
      microbiota at organ scale. Habitat strongly influenced gill and gut microbiota.
      In contrast, microbiota associated with remaining tissues was similar between
      group individuals suggesting that these communities are mostly autochthonous,
      i.e., Manila clam specific. Transplant experiment showed that improving living
      condition did not induce any change in microbiota associated with remaining
      tissues. In contrast, the reduction in individual habitat quality led to
      individuals in declining health as strongly suggested by the increase in
      phagocytosis activity and decrease in condition index together with the change in
      internal organ microbiota. This study provides a first description of the Manila
      clam holobiont which can withstand disturbance and respond opportunistically to
      improved environmental conditions. 

PMID- 26311129
TI  - Mechanism of altruism approach to blood donor recruitment and retention: a review
      and future directions.
AB  - Why do people donate blood? Altruism is the common answer. However, altruism is a
      complex construct and to answer this question requires a systematic analysis of
      the insights from the biology, economics and psychology of altruism. I term this
      the mechanism of altruism (MOA) approach and apply it here for understanding
      blood donor motivation. The answer also has enormous implications for the type of
      interventions we choose to adopt as a society. A MOA approach so far shows that
      blood donors are a mixture of (i) warm-glow givers (donation is emotionally
      rewarding) and (ii) reluctant altruists (cooperate rather than defect when free
      riding is high). Donors also show 'saintly sinning' with the extra 'moral
      currency' form blood donation allowing them to be less generous in other
      contexts. The MOA approach suggests why financial incentives, in terms of
      gifts/lottery tickets, are effective and suggests a number of novel interventions
      for donor recruitment: 'voluntary reciprocal altruism' and 'charitable
      incentivisation'. The MOA approach also highlights the need for an intervention
      developed specifically for recipients to allow them to show their gratitude to
      donors and for society to celebrate blood donation. It is suggests a 'Monument to
      Blood Donors' will achieve this. The approach suggests a number of novel research
      questions into (i) donor self-selection effects, (ii) conditional cooperation and
      (iii) construct overlap with Theory of Planned Behaviour (e.g. affective
      attitudes and warm-glow). The MOA offers a powerful way to understand blood donor
      motivations around altruism and develop theoretically driven interventions. 

PMID- 26311128
TI  - Plaque-associated lipids in Alzheimer's diseased brain tissue visualized by
      nonlinear microscopy.
AB  - By simultaneous coherent anti-Stokes Raman scattering (CARS) and 2-photon
      fluorescence microscopy of Thioflavin-S stained Alzheimer's diseased human brain
      tissues, we show evidence of lipid deposits co-localizing with fibrillar beta
      amyloid (Abeta) plaques. Two lipid morphologies can be observed; lamellar
      structures and coalescing macro-aggregates of sub-micron sizes to ~25 MUm. No
      significant lipid deposits were observed in non-fibrillar, diffuse plaques
      identified by Abeta immuno-staining. CARS microscopy of unlabeled samples
      confirms the lamellar and macro-aggregate lipid morphologies. The composition of
      the plaques was analyzed by CARS microspectroscopy and Raman microscopy;
      vibrational signatures of lipids with long acyl chains co-localize with the beta
      sheet vibrations. The lipid fluidity was evaluated from the CARS spectra,
      illustrating that the lipid composition/organization varies throughout the
      plaques. Altogether this indicates close amyloid-lipid interplay in fibrillar
      Abeta plaques, rendering them more dynamic compositions than previously believed
      and, hence, potential sources of toxic oligomers. 

PMID- 26311130
TI  - [Balloon dilation of the Eustachian tube in pediatric chronic obstructive
      Eustachian tube dysfunction patients].
AB  - OBJECTIVE: Balloon dilation of the Eustachian tube has recently been introduced
      as a novel and minimally invasive method for treating chronic obstructive
      Eustachian tube dysfunction. For the first time worldwide, we assessed the role
      of this technique in a large cohort of children with Eustachian tube dysfunction
      that did not respond to other treatments and in whom a tumor could be ruled out
      as the cause. STUDY DESIGN: This study is a retrospective analysis. METHODS: We
      retrospectively analyzed the medical records of 66 children (mean age 8.12 years,
      range 4-14 years) who underwent balloon dilation of the Eustachian tube using the
      Bielefeld balloon catheter. RESULTS: There were no complications during surgery.
      Clinical symptoms improved in more than 80% of the patients. No patient reported
      a deterioration of symptoms. Of the participating parents, over 80% were very
      satisfied or satisfied with the treatment outcome. CONCLUSION: Balloon dilation
      is a rapid, simple, and safe method for treatment of both adults and children
      with Eustachian tube dysfunction that does not respond to other treatments.
      Further studies, ideally multicenter studies, are required in order to optimize
      the definition of existing and potential new indications for this treatment
      approach, as well as to establish this treatment in the management of children
      with refractory chronic Eustachian tube dysfunction.

PMID- 26311131
TI  - Damage evaluation in graphene underlying atomic layer deposition dielectrics.
AB  - Based on micro-Raman spectroscopy (MURS) and X-ray photoelectron spectroscopy
      (XPS), we study the structural damage incurred in monolayer (1L) and few-layer
      (FL) graphene subjected to atomic-layer deposition of HfO2 and Al2O3 upon
      different oxygen plasma power levels. We evaluate the damage level and the
      influence of the HfO2 thickness on graphene. The results indicate that in the
      case of Al2O3/graphene, whether 1L or FL graphene is strongly damaged under our
      process conditions. For the case of HfO2/graphene, MURS analysis clearly shows
      that FL graphene is less disordered than 1L graphene. In addition, the damage
      levels in FL graphene decrease with the number of layers. Moreover, the FL
      graphene damage is inversely proportional to the thickness of HfO2 film.
      Particularly, the bottom layer of twisted bilayer (t-2L) has the salient features
      of 1L graphene. Therefore, FL graphene allows for controlling/limiting the degree
      of defect during the PE-ALD HfO2 of dielectrics and could be a good starting
      material for building field effect transistors, sensors, touch screens and solar
      cells. Besides, the formation of Hf-C bonds may favor growing high-quality and
      uniform-coverage dielectric. HfO2 could be a suitable high-K gate dielectric with
      a scaling capability down to sub-5-nm for graphene-based transistors. 

PMID- 26311132
TI  - EDITORIAL: Advances in Pharmaceutical Biotechnology.

PMID- 26311133
TI  - Editorial: Toward Personalized Treatment for Acute Myeloid Leukemia.

PMID- 26311134
TI  - Kinetic resolution of alkyne-substituted quaternary oxindoles via copper
      catalysed azide-alkyne cycloadditions.
AB  - The synthesis and kinetic resolution of quaternary oxindoles through copper
      catalysed azide-alkyne cycloadditions is presented. Selectivity factors (s) up to
      22.1 +/- 0.5 are reported. Enantioenriched alkynes and triazoles were obtained in
      >=80% enantiomeric excess (e.e.). 

PMID- 26311135
TI  - Rapid genetic divergence in response to 15 years of simulated climate change.
AB  - Genetic diversity may play an important role in allowing individual species to
      resist climate change, by permitting evolutionary responses. Our understanding of
      the potential for such responses to climate change remains limited, and very few
      experimental tests have been carried out within intact ecosystems. Here, we use
      amplified fragment length polymorphism (AFLP) data to assess genetic divergence
      and test for signatures of evolutionary change driven by long-term simulated
      climate change applied to natural grassland at Buxton Climate Change Impacts
      Laboratory (BCCIL). Experimental climate treatments were applied to grassland
      plots for 15 years using a replicated and spatially blocked design and included
      warming, drought and precipitation treatments. We detected significant genetic
      differentiation between climate change treatments and control plots in two
      coexisting perennial plant study species (Festuca ovina and Plantago lanceolata).
      Outlier analyses revealed a consistent signature of selection associated with
      experimental climate treatments at individual AFLP loci in P. lanceolata, but not
      in F. ovina. Average background differentiation at putatively neutral AFLP loci
      was close to zero, and genomewide genetic structure was associated neither with
      species abundance changes (demography) nor with plant community-level responses
      to long-term climate treatments. Our results demonstrate genetic divergence in
      response to a suite of climatic environments in reproductively mature populations
      of two perennial plant species and are consistent with an evolutionary response
      to climatic selection in P. lanceolata. These genetic changes have occurred in
      parallel with impacts on plant community structure and may have contributed to
      the persistence of individual species through 15 years of simulated climate
      change at BCCIL. 

PMID- 26311136
TI  - Embolisation of vascular renal tumour: an effective step to reduce peri-operative
      bleeding.

PMID- 26311137
TI  - The ominous side of a coronary fistula.

PMID- 26311138
TI  - Temporomandibular pain and jaw dysfunction at different ages covering the
      lifespan--A population based study.
AB  - BACKGROUND: Temporomandibular pain and jaw dysfunction can have a negative effect
      on daily life, but these conditions are not well recognized in the health care
      systems. The general aim was to examine the cross-sectional prevalence of
      frequent temporomandibular pain and jaw dysfunction in men and women across the
      lifespan. METHODS: The analysis was based on data from 137,718 individuals (mean
      age 35 years, SD 22.7) who answered three questions (3Q/TMD) included in the
      digital health declaration in the Public Dental Health care in the county of
      Vasterbotten, Sweden; Q1: 'Do you have pain in your temple, face, jaw or jaw
      joint once a week or more?'; Q2: 'Does it hurt once a week or more when you open
      your mouth or chew?'; and Q3: 'Does your jaw lock or become stuck once a week or
      more?' RESULTS: The prevalence of frequent temporomandibular pain (Q1) was 5.2%
      among women and 1.8% among men (p < 0.0001). The prevalence of frequent pain on
      jaw movement (Q2) was 2.5% among women and 0.9% among men (p < 0.0001). The
      prevalence of frequent locking of the jaw (Q3) was 2.7% among women and 1.2%
      among men (p < 0.0001). CONCLUSIONS: The study shows that the cross-sectional
      prevalence of temporomandibular pain and jaw dysfunction varies during the
      lifespan. For men and women, respectively, symptoms increase during adolescence,
      peak in middle age and then gradually diminish. The prevalence of these symptoms
      is significantly higher among women except from the first and last decades of a
      100-year lifespan.

PMID- 26311139
TI  - Different clinicopathologic features and favorable outcomes of patients with
      stage III left-sided colon cancer.
AB  - BACKGROUND: We evaluated the clinicopathologic features and outcomes of Taiwanese
      patients with right-sided versus left-sided colon cancer according to various
      cancer stages. METHODS: A total of 1095 patients with primary colorectal cancer
      (CRC) undergoing surgery at a single-institution were enrolled. We analyzed
      patient differences in terms of clinicopathologic features, overall survival (OS)
      and cancer-specific survival (CSS) of right- versus left-sided colon cancer.
      RESULTS: Right-sided colon cancers were noted in 249 (22.7%) patients, and left
      sided colon cancers were noted in 846 (77.3%) patients. Right-sided colon cancers
      were found to be significantly larger (P = 0.003) and poorly differentiated (P <
      0.001), while also exhibiting advanced depth of tumor invasion (P = 0.002) and
      advanced UICC/AJCC stage (P = 0.016). Patients with right-sided colon cancers had
      both poorer OS and CSS than those with left-sided colon cancers (P = 0.021 and
      0.023, respectively). However, analysis by various stages revealed significant OS
      and CSS differences (P = 0.002 and 0.002, respectively) between right-sided and
      left-sided colon cancers only in stage III patients. CONCLUSIONS: This study
      demonstrated poorer OS and CSS in patients with right-sided versus those with
      left-sided colon cancers, but significant differences were noted only in stage
      III patients.

PMID- 26311140
TI  - Assessing Differences in Risk Perceptions About Obesity Among "Normal-Weight" and
      "Overweight" Adolescents--A Qualitative Study.
AB  - OBJECTIVES: To assess the differences in risk perceptions of overweight/obese and
      normal-weight adolescents about obesity and associated risk factors. DESIGN:
      Qualitative study using focus group discussions (FGDs). SETTINGS: Five randomly
      selected schools from the South Indian city of Hyderabad. PARTICIPANTS: Seventy
      nine adolescents (ages 11-14 years) participated in 10 FGDs (5 each with
      overweight/obese and normal-weight groups). PHENOMENON OF INTEREST: Whether
      obesity-related risk perceptions differ with actual weight status or not.
      ANALYSIS: FGDs were recorded, transcribed, and manually coded for thematic
      analysis. Results were presented according to 6 themes. At each stage of coding
      and analysis, reports were read independently by 2-3 researchers and the inter
      coder reliability was high (ratio of number of agreements against the sum of
      agreements plus disagreements was over 90%). RESULTS: Adolescents across the
      groups had limited understanding of nutrition during adolescence as well as
      causes and consequences of obesity. The optimistic bias that they were less
      vulnerable compared to others to the risks of obesity was evident from
      perceptions of overweight groups. While overweight adolescents argued that
      obesity was hereditary, the normal-weight participants perceived "faulty food
      habits" and laziness as the reasons. Adolescents across the groups considered
      fruits and vegetables as healthy foods. CONCLUSIONS AND IMPLICATIONS: There were
      clear differences in perceptions of adolescents of different weight status.
      Employing the risk perception analysis framework, this study identified the
      following adolescent traits: responsive, avoidance, and indifference, which may
      be useful for developing nutrition communication programs.

PMID- 26311141
TI  - Demand for long acting contraceptive methods among married HIV positive women
      attending care at public health facilities at Bahir Dar City, Northwest Ethiopia.
AB  - BACKGROUND: The use of long acting contraceptive methods (LACMs) is one of the
      strategies for preventing mother-to-child transmission (MTCT) of HIV. Studies
      noted that significant proportion of unintended pregnancy among HIV positive
      women was due to contraceptive failure mainly of short term contraceptives. This
      highlights the need to use most effective types of modern contraception, long
      acting contraceptive. However, studies conducted on demand for long acting
      contraceptive methods in this particular group of people are scarce in Ethiopia.
      This study aimed to assess demand for long acting contraceptive methods and
      associated factors among married reproductive age women attending care at
      Antiretroviral treatment (ART) clinics in public health institutions at Bahir Dar
      City, Northwest Ethiopia. METHODS: Institution-based cross-sectional study was
      conducted among 654 systematically selected women attending care in ART clinics
      in public health facilities at Bahir Dar city from March to April, 2014. A
      structured and pretested interviewer administered questionnaire was used to
      collect data. Data were entered using EPI info version 3.5.3 and then exported to
      SPSS version 16 for analysis. Descriptive statistics were used to describe the
      socio-demographic and economic characteristics of the study participants.
      Logistic regression analyses were employed to identify factors associated with
      demand for long acting contraceptive methods. Odds ratios with 95 % CI were used
      to assess the presence and strength of association. RESULTS: A total of 654
      respondents have participated in the study (response rate 99. 09 %). The demand
      for long acting contraceptive methods was 36.7 % (95 % CI: 33.2 %, 40.6 %). The
      odds of demand for LACMs among HIV positive women who were living in urban were
      three times [AOR = 3.05, 95 % CI: 1.34, 6.89] higher than those who were living
      in rural. The odds of demand for LACMs among the respondents who were in
      elementary educational level were two times [AOR = 2.31, 95 % CI: 1.34, 3.99]
      more likely as compared to those who had no formal education. HIV positive women
      who had four or more alive children were almost four times [AOR = 3.86, 95 % CI:
      1.62, 9.20] more likely to have demand for LACMs than those who had one child or
      had no child at all. Those who had desire to give birth after 2 years were nearly
      six times more likely [AOR = 5.68, 95 % CI: 3.05, 11.58] to have demand for LACMs
      and women who had no birth intension were eight times more likely [AOR = 7.78, 95
      % CI: 4.15, 14.58] to have demand for LACMs as compared to those who had
      intention to have birth within 2 years. Women who had past experience on LACMs
      had six times more likely [AOR = 6.35, 95 % CI: 4.09, 9.87] to have demand for
      LACMs than those who hadn't any experience. The odds of demand for long acting
      contraceptive methods among HIV positive women who had heard myths about LACMs
      was 55 % less [AOR = 0.45, 95 % CI: 0.29, 0.68] than those women who hadn't heard
      myths. CONCLUSIONS: Demand for long acting contraceptive methods in this study
      was low. There was high unmet need for LACMs. Myths about LACMs were common in
      the community and were the major barriers for the promotion and utilization of
      the methods. Demand creation on LACMs and bringing attitudinal change related to
      myths through provision of information, education and communication are
      recommended. Moreover, giving greater attention for rural residents is important.

PMID- 26311142
TI  - Quality of life after surgical decompression for a space-occupying middle
      cerebral artery infarct: A cohort study.
AB  - BACKGROUND: In patients with a space-occupying middle cerebral artery (MCA)
      infarct surgical decompression reduces the risk of death, but increases the
      chance of survival with severe disability. We assessed quality of life (QoL),
      symptoms of depression, and caregiver burden at long-term follow-up. METHODS:
      Patients treated in two academic centres between 2007 and 2012 were included.
      Follow-up was at least six months. Patients and caregivers were interviewed
      separately. QoL was assessed with a visual analogue scale and the 36-item Short
      Form health survey (SF-36); depression with the Hospital Anxiety and Depression
      Scale; and caregiver burden with the Caregiver Strain Index. RESULTS: Twenty five
      patients were enrolled, of whom seven had an infarct in the dominant hemisphere.
      After a median follow-up of 26 months (IQR 11-46) the median SF-36 mental
      component score was 54.4 (IQR 45-60), indicating a mental QoL comparable to that
      in the general population. The median SF-36 physical component score was 32.7
      (IQR 22-38), indicating a worse physical QoL. Dominance of the hemisphere did not
      influence QoL. 79 % of patients and 65 % of caregivers would, in retrospect,
      again choose for surgery. 26 % of patients had signs of depression and 64 % of
      caregivers were substantially burdened in their daily life. CONCLUSIONS: Mental
      QoL after surgical decompression for space-occupying MCA infarct is comparable to
      that in the general population, whereas physical QoL is worse. Dominance of the
      hemisphere did not influence QoL. The majority of caregivers experience
      substantial burden. Most patients and caregivers stand by their decision for
      hemicraniectomy.

PMID- 26311143
TI  - Frequency, nature and outcomes of hospital admissions in centenarians in an area
      of North-East England.
AB  - AIMS: There are few data on the use of hospital services by centenarians living
      in the UK. In the present study, we recorded the frequency, nature and outcomes
      of hospital admissions in centenarians in an area of North-East England. METHODS:
      Data regarding hospital attendance in centenarians in Northumberland and North
      Tyneside, covered by one National Health Service Trust, were collected. For the
      years 2010-2013, demographics, frequency of admission and length of hospital stay
      data were collected. Medical notes for those admitted in 2011 were reviewed, and
      data extracted relating to diagnosis, medications and past medical history.
      RESULTS: Across the 4 years of the study, there were 349 hospital attendances of
      centenarians. A total of 264 of these attendances resulted in admission with an
      overnight stay. In 2011, there were 107 attendances, 75 of which (in 54 unique
      patents) resulted in admission and an overnight stay. The unique patients
      admitted represented 41.5% of the centenarians living in the catchment area. The
      most common primary reason for admission in centenarians was respiratory tract
      infection, though falls were a primary or secondary reason for admission in 41.3%
      of centenarians. There were 11 in-hospital deaths in 2011, and a further seven
      deaths within 30 days of discharge. The median number of medications taken on
      admission and discharge was six. CONCLUSIONS: Almost half of the centenarians
      living in the catchment area were admitted to hospital during 2011. Over 25% of
      admissions either died in hospital or within 30 days of discharge. Geriatr
      Gerontol Int 2016; 16: 969-975.

PMID- 26311144
TI  - Correlation between mass and volume of collected blood with positivity of blood
      cultures.
AB  - BACKGROUND: The collection of blood cultures is an extremely important method in
      the management of patients with suspected infection. Microbiology laboratories
      should monitor blood culture collection. METHODS: Over an 8-month period we
      developed a prospective, observational study in an adult Intensive Care Unit
      (ICU). We correlated the mass contained in the blood vials with blood culture
      positivity and we also verified the relationship between the mass of blood and
      blood volume collected for the diagnosis of bloodstream infection (BSI), as well
      as we explored factors predicting positive blood cultures. RESULTS: We evaluated
      345 patients with sepsis, severe sepsis or septic shock for whom blood culture
      bottles were collected for the diagnosis of BSI. Of the 55 patients with BSI,
      40.0% had peripheral blood culture collection only. BSIs were classified as
      nosocomial in 34.5%. In the multivariate model, the blood culture mass (in grams)
      remained a significant predictor of positivity, with an odds ratio 1.01 (i.e.,
      for each additional 1 mL of blood collected there was a 1% increase in
      positivity; 95% CI 1.01-1.02, p = 0.001; Nagelkerke R Square [R(2)] = 0.192). For
      blood volume collected, the adjusted odds ratio was estimated at 1.02 (95% CI:
      1.01-1.03, p < 0.001; R(2) = 0.199). For each set of collected blood cultures
      beyond one set, the adjusted odds ratio was estimated to be 1.27 (95% CI: 1.14
      1.41, p < 0.001; R(2) = 0.221). CONCLUSIONS: Our study was a quality improvement
      project that showed that microbiology laboratories can use the weight of blood
      culture bottles to determine if appropriate volume has been collected to improve
      the diagnosis of BSI.

PMID- 26311145
TI  - Optimizing testing methods and collection of reference data for differentiating
      critical illness polyneuropathy from critical illness MYOPATHIES.
AB  - INTRODUCTION: In severe acute quadriplegic myopathy in intensive care unit (ICU)
      patients, muscle fibers are electrically inexcitable; in critical illness
      polyneuropathy, the excitability remains normal. Conventional electrodiagnostic
      methods do not provide the means to adequately differentiate between them. In
      this study we aimed to further optimize the methodology for the study of
      critically ill ICU patients and to create a reference database in healthy
      controls. METHODS: Different electrophysiologic protocols were tested to find
      sufficiently robust and reproducible techniques for clinical diagnostic
      applications. RESULTS: Many parameters show large test-retest variability within
      the same healthy subject. Reference values have been collected and described as a
      basis for studies of weakness in critical illness. CONCLUSIONS: Using the ratio
      of neCMAP/dmCMAP (response from nerve and direct muscle stimulation), refractory
      period, and stimulus-response curves may optimize the electrodiagnostic
      differentiation of patients with critical illness myopathy from those with
      critical illness polyneuropathy.

PMID- 26311146
TI  - Transforming growth factor-beta1 regulates human renal proximal tubular
      epithelial cell susceptibility to natural killer cells via modulation of the
      NKG2D ligands.
AB  - Transforming growth factor-beta (TGF-beta) has a significant role in the response
      to injury and tissue repair, and it has been detected in various cell types.
      However, the mechanism by which it regulates the response to ischemia-reperfusion
      injury (IRI) and manipulates natural killer (NK) cells is not well understood. In
      the present study, TGF-beta modulated NK cell function, thereby promoting
      recovery from renal IRI. Human renal proximal tubular epithelial cells (HK-2)
      treated with TGF-beta exhibited increased surface and intracellular expression of
      the NK group 2 member D (NKG2D) ligand MICA. This increased surface expression of
      MICA inhibited NK cell cytotoxicity to the HK-2 cells. In addition, an enzyme
      linked immunosorbent assay revealed that TGF-beta treatment evidently increased
      the amount of soluble MICA released into the culture supernatant from HK-2 cells.
      Taken together, these findings suggest that TGF-beta-induced release of soluble
      MICA leads to downregulation of NKG2D, thereby preventing NK cell-mediated
      cytotoxicity toward renal proximal tubular epithelial cells in renal IRI, which
      in turn improves the survival of these cells. 

PMID- 26311147
TI  - Anti-Mullerian hormone, the holy grail for fertility counselling in the general
      population?

PMID- 26311148
TI  - Ovarian reserve assessment in users of oral contraception seeking fertility
      advice on their reproductive lifespan.
AB  - STUDY QUESTION: To what extent does oral contraception (OC) impair ovarian
      reserve parameters in women who seek fertility assessment and counselling to get
      advice on whether their remaining reproductive lifespan is reduced? SUMMARY
      ANSWER: Ovarian reserve parameters defined by anti-Mullerian hormone (AMH),
      antral follicle count (AFC) and ovarian volume were found to be significantly
      decreased by 19% (95% CI 9.1-29.3%), 18% (95% CI 11.2-24.8%) and 50% (95% CI 45.1
      53.7%) among OC users compared with non-users. WHAT IS KNOWN ALREADY: AMH and AFC
      have proved to be reliable predictors of ovarian ageing. In women, AMH declines
      with age and data suggest a relationship with remaining reproductive lifespan and
      age at menopause. OC may alter parameters related to ovarian reserve assessment
      but the extent of the reduction is uncertain. STUDY DESIGN, SIZE, DURATION: A
      cross-sectional study of 887 women aged 19-46 attending the Fertility Assessment
      and Counselling Clinic (FACC) from 2011 to 2014 comparing ovarian reserve
      parameters in OC users with non-OC users. PARTICIPANTS/MATERIALS, SETTING,
      METHODS: The FAC Clinic was initiated to provide individual fertility assessment
      and counselling. All women were examined on a random cycle day by a fertility
      specialist. Consultation included; transvaginal ultrasound (AFC, ovarian volume,
      pathology), a full reproductive history and AMH measurement. Women were grouped
      into non-users and users of OC (all combinations of estrogen-progestin products
      and the contraceptive vaginal ring). Non-users included women with an
      intrauterine device (IUD) or no hormonal contraception. MAIN RESULTS AND THE ROLE
      OF CHANCE: Of the 887 women, 244 (27.5%) used OC. In a linear regression analyses
      adjusted for age, ovarian volume was 50% lower (95% CI 45.1-53.7%), AMH was 19%
      lower (95% CI 9.1-29.3%), and AFC was 18% lower (95% CI 11.2-24.8%) in OC users
      compared with non-users. Comparison of AMH at values of <10 pmol/l OC was found
      to have a significant negative influence on AMH (OR 1.6, 95% CI 1.1; 2.4, P =
      0.03). Furthermore, we found a significant decrease in antral follicles sized 5-7
      mm (P < 0.001) and antral follicles sized 8-10 mm (P < 0.001) but an increase in
      antral follicles sized 2-4 mm (P = 0.008) among OC users. The two groups (OC
      users versus non-users) were comparable regarding age, BMI, smoking and maternal
      age at menopause. LIMITATIONS, REASON FOR CAUTION: The study population comprised
      women attending the FAC Clinic. Recruitment was based on self-referral, which
      could imply a potential selection bias. Ovarian reserve was examined at a random
      cycle day. However, both AMH and AFC can be assessed independently of the
      menstrual cycle. The accuracy in predicting residual reproductive lifespan is
      still needed in both users and non-users of OC. WIDER IMPLICATIONS OF THE
      FINDINGS: OC has a major impact on the ovarian volume, and a moderate impact on
      AFC and AMH with a shift towards the smaller sized antral follicle subclasses.
      The most evident reduction occurs in the antral follicles of 5-7 and 8-10 mm with
      the highest number of AMH secreting granulosa cells. It is essential to be aware
      of the impact of OC use on ovarian reserve parameters when guiding OC users on
      their fertility status and reproductive lifespan. STUDY FUNDING/COMPETING
      INTERESTS: The FAC Clinic was established in 2011 as part of the ReproHigh
      collaboration. This study received funding through the Capital Region Research
      Fund and by EU-regional funding. There are no competing interests. TRIAL
      REGISTRATION NUMBER: The biobank connected to FAC Clinic is approved by the
      Scientific Ethical Committee (H-1-2011-081).

PMID- 26311149
TI  - A simple risk stratification model that predicts 1-year postoperative mortality
      rate in patients with solid-organ cancer.
AB  - This study aimed to construct a scoring system developed exclusively from the
      preoperative data that predicts 1-year postoperative mortality in patients with
      solid cancers. A total of 20,632 patients who had a curative resection for solid
      organ cancers between 2007 and 2012 at Chang Gung Memorial Hospital Linkou
      Medical Center were included in the derivation cohort. Multivariate logistic
      regression analysis was performed to develop a risk model that predicts 1-year
      postoperative mortality. Patients were then stratified into four risk groups (low
      , intermediate-, high-, and very high-risk) according to the total score (0-43)
      form mortality risk analysis. An independent cohort of 16,656 patients who
      underwent curative cancer surgeries at three other hospitals during the same
      study period (validation cohort) was enrolled to verify the risk model. Age,
      gender, cancer site, history of previous cancer, tumor stage, Charlson
      comorbidity index, American Society of Anesthesiologist score, admission type,
      and Eastern Cooperative Oncology Group performance status were independently
      predictive of 1-year postoperative mortality. The 1-year postoperative mortality
      rates were 0.5%, 3.8%, 14.6%, and 33.8%, respectively, among the four risk groups
      in the derivation cohort (c-statistic, 0.80), compared with 0.9%, 4.2%, 14.6%,
      and 32.6%, respectively, in the validation cohort (c-statistic, 0.78). The risk
      stratification model also demonstrated good discrimination of long-term survival
      outcome of the four-tier risk groups (P < 0.01 for both cohorts). The risk
      stratification model not only predicts 1-year postoperative mortality but also
      differentiates long-term survival outcome between the risk groups.

PMID- 26311151
TI  - Parsing Physiological Functions of Erythropoietin One Domain at a Time.
AB  - A domain of erythropoietin (EPO), separate from the domain involved in red blood
      cell development, has been identified. This region of EPO has anti-inflammatory
      and neuroprotective effects. Use of a peptide sequence from this region provides
      the potential for an effective therapeutic without effects on erythropoiesis.

PMID- 26311150
TI  - Cannabinoids and Schizophrenia: Risks and Therapeutic Potential.
AB  - A convergence of evidence shows that use of Cannabis sativa is associated with
      increased risk of developing psychotic disorders, including schizophrenia, and
      earlier age at which psychotic symptoms first manifest. Cannabis exposure during
      adolescence is most strongly associated with the onset of psychosis amongst those
      who are particularly vulnerable, such as those who have been exposed to child
      abuse and those with family histories of schizophrenia. Schizophrenia that
      develops after cannabis use may have a unique clinical phenotype, and several
      genetic polymorphisms may modulate the relationship between cannabis use and
      psychosis. The endocannabinoid system has been implicated in psychosis both
      related and unrelated to cannabis exposure, and studying this system holds
      potential to increase understanding of the pathophysiology of schizophrenia.
      Anandamide signaling in the central nervous system may be particularly important.
      Delta(9)-Tetrahydrocannabinol in cannabis can cause symptoms of schizophrenia
      when acutely administered, and cannabidiol (CBD), another compound in cannabis,
      can counter many of these effects. CBD may have therapeutic potential for the
      treatment of psychosis following cannabis use, as well as schizophrenia, possibly
      with better tolerability than current antipsychotic treatments. CBD may also have
      anti-inflammatory and neuroprotective properties. Establishing the role of CBD
      and other CBD-based compounds in treating psychotic disorders will require
      further human research.

PMID- 26311152
TI  - Impact of DBP on histology and expression of HSP 70 in gill and liver tissue of
      Cyprinus carpio.
AB  - Di-n-butyl phthalate (DBP) widely used plasticizer in the plastic industry,
      affects regulation of the endocrine system and causes toxicity in animals. In the
      present study, the aim was to study the toxic effects/damages of DBP exposure
      using Hsp70 levels and histopathological changes in Carp liver and gill. Hsp70
      expression levels were assessed as specific biomarker of in vivo ecotoxicological
      stress. Carp (Cyprinus carpio) were exposed to sub-lethal concentration of DBP
      (di-n-butyl phthalate, 1 mg/L) for 4, 24 and 96 h. Gill and liver tissues were
      evaluated histopathologically and RNA quantifications for Hsp70 expression levels
      were carried out using a two-step real-time RT-PCR. In liver, a rapid but non
      significant increase in mRNA levels in the first 4 h was observed. mRNA levels
      significantly increased up to 2-3 fold after 24 and 96 h (p < 0.05). However,
      irregular mRNA level changes were also recorded: Gill specific and time-dependent
      regulation of Hsp70 expression were 4-5 fold inhibition after 4 and 24 h (p <
      0.05), then increased up to 4 fold after 96 h (p < 0.05). Histopathological
      findings support altered transcription results as: Epithelial lifting,
      hyperplasia, fusion of secondary lamellae, telangiectasis, passive hyperemia and
      hydropic degeneration. Significant alterations of Hsp70 levels were likely due to
      a tissue specific response against chemical stress, cellular damage and lesions
      due to DBP. Carp was found to be a suitable experimental model for toxicology,
      and Hsp70 mRNA levels are reliable, specific biomarkers. 

PMID- 26311154
TI  - Molecular cloning, characterization and expression analysis of 3-hydroxy-3
      methylglutaryl coenzyme A reductase gene from Centella asiatica L.
AB  - 3-Hydroxy-3-methylglutaryl-CoA reductases (HMGR) plays an important role in
      catalyzing the first committed step of isoprenoid biosynthesis in the mevelonic
      (MVA) pathway (catalyzes the conversion of HMG-CoA to MVA) in plants. The present
      manuscript reports the full length cDNA cloning of HMGR (CaHMGR, GenBank
      accession number: KJ939450.2) and its characterization from Centella asiatica.
      Sequence analysis indicated that the cDNA was of 1965 bp, which had an open
      reading frame of 1617 bp and encoded a protein containing 539 amino-acids with a
      mol wt of 57.9 kDa. A BLASTp search against non-redundant (nr) protein sequence
      showed that C. asiatica HMGR (CaHMGR) has 65-81% identity with HMGRs from
      different plant species and multi-alignment comparison analysis showed the
      presence of two motif each corresponding to HMG-CoA-binding and NADP(H)-binding.
      The Conserved Domain Database analysis predicted that CaHMGR belongs to Class I
      hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase. Three-dimensional modeling
      confirmed the novelty of CaHMGR with a spatial structure similar to Homo sapiens
      (PDB id: 1IDQ8_A). Tissue Expression analysis indicates that CaHMGR is ubiquitous
      albeit differentially expressed among different tissues analysed, Strong
      expression was recorded in the nodes and leaves and low in the roots. The present
      investigation confirmed that nodes are vital to terpenoid synthesis in C.
      asiatica. Thus, the cloning of full length CDS, characterization and structure
      function analysis of HMGR gene in Centella facilitate to understand the HMGR's
      functions and regulatory mechanisms involved in mevalonate pathway in C. asiatica
      at genetic level.

PMID- 26311153
TI  - Anticarcinogenic action of quercetin by downregulation of phosphatidylinositol 3
      kinase (PI3K) and protein kinase C (PKC) via induction of p53 in hepatocellular
      carcinoma (HepG2) cell line.
AB  - Protein kinase C (PKC) is a key regulator of cell growth and differentiation in
      mammalian cells and hyperactivation of PKC is believed to play an important role
      in tumor progression. PKC is downstream to signaling protein of
      phosphatidylinositol 3-Kinase (PI3K), a known up-regulator of cell proliferation
      and survival. Accumulation of reactive oxygen species (ROS) triggers oxidative
      stress in the tumor microenvironment, leading to the hyperactivation of various
      oxidative stress-stimulated signaling molecules. Quercetin (QUE) is a naturally
      occurring dietary flavonoid having antioxidant properties. QUE is reported to
      show antitumor activity both in vitro and in vivo; however, the molecular
      mechanism is yet to be thoroughly explored. HepG2 cells display cellular
      functions similar to the normal hepatocytes with high degree of morphological and
      functional differentiation, therefore HepG2 cell line is chosen as the suitable
      model for drug targeting. Present study is aimed to establish the signaling
      pathway involved in the anticarcinogenic action of QUE in HepG2 cell line. HepG2
      cells were treated with different doses of QUE. Protein level and gene expression
      were analysed by Western blotting and RT-PCR, respectively. PKC activity was
      measured by non-radioactive-tagged phosphorylation. Results showed downregulation
      of expression of PI3K, PKC, COX-2 and ROS caused by QUE. Additionally, QUE
      enhanced the expression of p53 and BAX in HepG2 cells. Overall, results of the
      current study suggested that QUE elicited anticarcinogenic action by upregulation
      of p53 and BAX in HepG2 cells via downregulation of ROS, PKC, PI3K and COX-2,
      confirming our earlier report on the animal model. 

PMID- 26311156
TI  - Wide complex tachycardia after bupropion overdose.
AB  - Here we describe a wide complex tachycardia after bupropion overdose that was
      responsive to sodium bicarbonate. This rhythm was likely secondary to bupropion
      induced sodium channel blockade and corrected QT interval (QTc) prolongation. It
      is critical for the emergency medicine physician to recognize that a wide complex
      rhythm in a patient with bupropion overdose may be secondary to sodium channel
      toxicity and prolonged QTc as this rhythm may be responsive to sodium
      bicarbonate. Identifying this rhythm as purely ventricular tachycardia can lead
      to the administration of medications such as amiodarone that may further prolong
      QTc and contribute to sodium channel blockade, exacerbating bupropion-induced
      cardiotoxicity.

PMID- 26311155
TI  - Mindfulness-based cognitive therapy (MBCT) for multiple chemical sensitivity
      (MCS): Results from a randomized controlled trial with 1 year follow-up.
AB  - OBJECTIVE: Multiple chemical sensitivity (MCS) is a medically unexplained
      condition characterized by symptoms from multiple organ systems following the
      perception of common odorants. The condition can cause severe functional
      impairment for afflicted individuals. The aim of this study was to assess the
      effects of mindfulness-based cognitive therapy (MBCT) for individuals with MCS.
      METHODS: The intention-to-treat sample (ITT) included 69 individuals who had been
      randomized to either MBCT or treatment as usual (TAU). The primary outcome
      measure was the Quick Environmental Exposure and Sensitivity Inventory (QEESI),
      which measures the following aspects of MCS: impact of MCS on daily life,
      symptoms, and reactions following chemical exposures. Secondary outcome measures
      included the Brief Illness Perception Questionnaire (BIPQ) and the anxiety and
      depression subscales of the symptom checklist 92 (SCL-92). Participants were
      assessed at baseline and post treatment, and at follow-up periods of 6- and 12
      months. RESULTS: We found no effect of MBCT on the primary outcome, nor did we
      find an effect on levels of depression or anxiety. We did, however, find positive
      changes in illness perceptions, which were sustained at 12-month follow-up.
      Dropout rates were low, suggesting MBCT was well received and regarded as an
      acceptable intervention by individuals with MCS. CONCLUSIONS: Overall, these
      results suggest that MBCT does not change overall illness status in individuals
      with MCS, but that MBCT positively changes emotional and cognitive
      representations. Possible explanations for these results are discussed.

PMID- 26311157
TI  - The jellyfish buffet: jellyfish enhance seabird foraging opportunities by
      concentrating prey.
AB  - High levels of jellyfish biomass have been reported in marine ecosystems around
      the world, but understanding of their ecological role remains in its infancy.
      Jellyfish are generally thought to have indirect negative impacts on higher
      trophic-level predators, through changes in lower trophic pathways. However, high
      densities of jellyfish in the water column may affect the foraging behaviour of
      marine predators more directly, and the effects may not always be negative. Here,
      we present novel observations of a diving seabird, the thick-billed murre,
      feeding on fish aggregating among the long tentacles of large jellyfish, by using
      small video loggers attached to the birds. We show that the birds encountered
      large jellyfish, Chrysaora melanaster, during most of their dives, commonly fed
      on fish associated with jellyfish, and appeared to specifically target jellyfish
      with a high number of fish aggregating in their tentacles, suggesting the use of
      jellyfish may provide significant energetic benefits to foraging murres. We
      conclude that jellyfish provide feeding opportunities for diving seabirds by
      concentrating forage fish, and that the impacts of jellyfish on marine ecosystems
      are more complex than previously anticipated and may be beneficial to seabirds. 

PMID- 26311158
TI  - Escaping peril: perceived predation risk affects migratory propensity.
AB  - Although migratory plasticity is increasingly documented, the ecological drivers
      of plasticity are not well understood. Predation risk can influence migratory
      dynamics, but whether seasonal migrants can adjust their migratory behaviour
      according to perceived risk is unknown. We used electronic tags to record the
      migration of individual roach (Rutilus rutilus), a partially migratory fish, in
      the wild following exposure to manipulation of direct (predator presence/absence)
      and indirect (high/low roach density) perceived predation risk in experimental
      mesocosms. Following exposure, we released fish in their lake summer habitat and
      monitored individual migration to connected streams over an entire season.
      Individuals exposed to increased perceived direct predation risk (i.e. a live
      predator) showed a higher migratory propensity but no change in migratory timing,
      while indirect risk (i.e. roach density) affected timing but not propensity
      showing that elevated risk carried over to alter migratory behaviour in the wild.
      Our key finding demonstrates predator-driven migratory plasticity, highlighting
      the powerful role of predation risk for migratory decision-making and dynamics. 

PMID- 26311159
TI  - Stressful colours: corticosterone concentrations in a free-living songbird vary
      with the spectral composition of experimental illumination.
AB  - Organisms have evolved under natural daily light/dark cycles for millions of
      years. These cycles have been disturbed as night-time darkness is increasingly
      replaced by artificial illumination. Investigating the physiological consequences
      of free-living organisms in artificially lit environments is crucial to determine
      whether nocturnal lighting disrupts circadian rhythms, changes behaviour, reduces
      fitness and ultimately affects population numbers. We make use of a unique, large
      scale network of replicated field sites which were experimentally illuminated at
      night using lampposts emanating either red, green, white or no light to test
      effect on stress hormone concentrations (corticosterone) in a songbird, the great
      tit (Parus major). Adults nesting in white-light transects had higher
      corticosterone concentrations than in the other treatments. We also found a
      significant interaction between distance to the closest lamppost and treatment
      type: individuals in red light had higher corticosterone levels when they nested
      closer to the lamppost than individuals nesting farther away, a decline not
      observed in the green or dark treatment. Individuals with high corticosterone
      levels had fewer fledglings, irrespective of treatment. These results show that
      artificial light can induce changes in individual hormonal phenotype. As these
      effects vary considerably with light spectrum, it opens the possibility to
      mitigate these effects by selecting street lighting of specific spectra. 

PMID- 26311160
TI  - Hatching late in the season requires flexibility in the timing of song learning.
AB  - Most songbirds learn their songs from adult tutors, who can be their father or
      other male conspecifics. However, the variables that control song learning in a
      natural social context are largely unknown. We investigated whether the time of
      hatching of male domesticated canaries has an impact on their song development
      and on the neuroendocrine parameters of the song control system. Average age
      difference between early- and late-hatched males was 50 days with a maximum of 90
      days. Song activity of adult tutor males decreased significantly during the
      breeding season. While early-hatched males were exposed to tutor songs for on
      average the first 99 days, late-hatched peers heard adult song only during the
      first 48 days of life. Remarkably, although hatching late in the season
      negatively affected body condition, no differences between both groups of males
      were found in song characteristics either in autumn or in the following spring.
      Similarly, hatching date had no effect on song nucleus size and circulating
      testosterone levels. Our data suggest that late-hatched males must have undergone
      accelerated song development. Furthermore, the limited tutor song exposure did
      not affect adult song organization and song performance. 

PMID- 26311161
TI  - Local expression of AP/AngIV/IRAP and effect of AngIV on glucose-induced
      epithelial transport in human jejunal mucosa.
AB  - BACKGROUND: Recently it was shown that the classic renin-angiotensin system (RAS)
      is locally expressed in small intestinal enterocytes and exerts autocrine control
      of glucose transport. The aim of this study was to investigate if key components
      for the Angiotensin III (AngIII) and IV (AngIV) formation enzymes and the AngIV
      receptor, insulin-regulated aminopeptidase (IRAP), are present in the healthy
      jejunal mucosa. A second aim was to investigate AngIV effects on glucose-induced
      mucosal transport in vitro. MATERIAL AND METHODS: Enteroscopy with mucosal biopsy
      sampling was performed in healthy volunteers. ELISA, Western blotting and
      immunohistochemistry were used to assess the protein levels and localization. The
      functional effect of AngIV was examined in Ussing chambers. RESULTS: The
      substrate Angiotensin II, the enzymes aminopeptidases-A, B, M as well as IRAP
      were detected in the jejunal mucosa. Immunohistochemistry localized the enzymes
      to the apical brush-border membrane whereas IRAP was localized in the subapical
      cytosolic compartment in the enterocyte. AngIV increased the glucose-induced
      electrogenic transport in vitro. CONCLUSION: The present study indicates the
      presence of substrates and enzymes necessary for AngIV formation as well as the
      receptor IRAP in the jejunal mucosa. The functional data suggest that AngIV
      regulates glucose uptake in the healthy human small intestine.

PMID- 26311162
TI  - Cystatin C as a potential predictor of osteoprotegerin levels in healthy men, a
      cross-sectional, observational study.
AB  - BACKGROUND: The aim of the present study is to evaluate serum osteoprotegerin
      (OPG) and soluble receptor activator of nuclear factor kappaB ligand (sRANKL)
      levels in a randomly selected male cohort over 50 years of age and its
      association with cystatin C, a cysteine proteinase inhibitor that decreases
      formation of osteoclasts by interfering at a late stage of pre-osteoclast
      differentiation, apart from being a marker of renal function independent of
      gender, muscle mass and age; in addition to known predictors such as age, sex
      hormones, vitamin D, bone mineral density (BMD) and biochemical markers of bone
      turnover. METHODS: We determined serum OPG and sRANKL levels and examined its
      relationship with cystatin C, age, osteocalcin, C-terminal telopeptides of type-I
      collagen, procollagen type 1 amino-terminal propeptide, 25-hydroxyvitamin D,
      parathyroid hormone, total 17beta-estradiol (E2), total testosterone and L1-L4
      (LS) and femur neck (FN) BMD data available from 194 (age, range: 51-81 years)
      randomly selected ambulatory men belonging to the HunMen cohort. RESULTS: OPG
      correlated significantly with age (Spearman's rho (r) = 0.359, p < 0.001),
      cystatin C (r = 0.298, p < 0.001), E2 (r = 0.160, p = 0.028) and free
      testosterone index (FTI) (r = -0.230, p = 0.001). Compared to the middle-aged
      (age: <= 59 years, n = 98), older men (age > 59 years, n = 96) had significantly
      higher serum OPG (4.6 pmol/L vs. 5.4 pmol/L; p < 0.001), and lower sRANKL (0.226
      pmol/L vs. 0.167 pmol/L; p = 0.048) levels. The older men showed a significant
      correlation between serum OPG levels and cystatin C (Spearman's rho = 0.322, p =
      0.002), and E2 (Spearman's rho = 0.211, p = 0.043). Including cystatin C and E2
      in a regression model showed that cystatin C (standard regression coefficient
      (beta) = 0.345; p = 0.002) was the only significant predictor of serum OPG levels
      in the older men. CONCLUSIONS: The results of this study demonstrated that in
      addition to age (which was the stronger predictor), other modifiable factors such
      as cystatin C, FTI and E2 were also significant predictors of OPG, and that the
      association between cystatin C and OPG was more evident with increased age (older
      age group). As such, cystatin C is a significant predictor of OPG independently
      of age, FTI and E2.

PMID- 26311163
TI  - Making the Oxford Hip and Knee Scores meaningful at the patient level through
      normative scoring and registry data.
AB  - OBJECTIVES: The Oxford Hip and Knee Scores (OHS, OKS) have been demonstrated to
      vary according to age and gender, making it difficult to compare results in
      cohorts with different demographics. The aim of this paper was to calculate
      reference values for different patient groups and highlight the concept of
      normative reference data to contextualise an individual's outcome. METHODS: We
      accessed prospectively collected OHS and OKS data for patients undergoing lower
      limb joint arthroplasty at a single orthopaedic teaching hospital during a five
      year period. T-scores were calculated based on the OHS and OKS distributions.
      RESULTS: Data were obtained from 3203 total hip arthroplasty (THA) patients and
      2742 total knee arthroplasty (TKA) patients. The mean age of the patient was 68.0
      years (sd 11.3, 58.4% women) in the THA group and in 70.2 (sd 9.4; 57.5% women)
      in the TKA group. T-scores were calculated for age and gender subgroups by
      operation. Different T-score thresholds are seen at different time points pre and
      post surgery. Values are further stratified by operation (THA/TKA) age and
      gender. CONCLUSIONS: Normative data interpretation requires a fundamental shift
      in the thinking as to the use of the Oxford Scores. Instead of reporting actual
      score points, the patient is rated by their relative position within the group of
      all patients undergoing the same procedure. It is proposed that this form of
      transformation is beneficial (a) for more appropriately comparing different
      patient cohorts and (b) informing an individual patient how they are progressing
      compared with others of their age and gender. Cite this article: Bone Joint Res
      2015;4:137-144.

PMID- 26311164
TI  - Altitudes of residential areas affect salt intake in a rural area in Japan: a
      Shimane CoHRE Study.
AB  - There is increasing evidence of an association between residential environments
      and hypertension. As shown in our previous study, the inconvenience of the
      locations of residential areas may be one of the factors influencing the blood
      pressures of inhabitants. Salt intake is one of the likely mediators between
      inconvenience and hypertension. Therefore, in this study, we evaluated the
      association between the altitudes of residential areas and salt intake in a rural
      Japanese region because altitude may be one of the proxies for inconvenience. In
      this cross-sectional study, 1016 participants living in a mountainous region in
      Japan were recruited during health examinations. The altitude of each
      participant's residence was estimated using a geographic information system.
      Subjects were divided into quartile groups according to the altitudes of their
      residences. To evaluate salt intake, we employed the 24-h salt intake estimation
      of Kawano et al. (e24-h salt intake) and the urinary sodium-to-potassium ratio
      (uNa/K). Linear regression analyses indicated that altitude was an independent
      factor influencing both e24-h salt intake and uNa/K after adjustments for age,
      sex, body mass index, physical activity, alcohol consumption, triglycerides and
      county of residence. The same result was observed when the subjects who did not
      take antihypertensive medications were analyzed (N=633). The present study
      indicated that altitude of residence had a significant positive influence on salt
      intake in a rural area of Japan. 

PMID- 26311165
TI  - Parity as a factor affecting the white-coat effect in pregnant women: the BOSHI
      study.
AB  - Parity has previously been reported to affect the difference in blood pressure
      (BP) measured in the office and at home, also known as the white-coat effect,
      during pregnancy. The objective of this study was to identify possible factors
      that cause the white-coat effect during pregnancy, focusing on parity. In total,
      530 pregnant women (31.3+/-4.7 years old) who delivered at a maternal clinic were
      eligible for the study. The association between parity and the white-coat effect
      (clinic BP compared with home BP) was investigated for each trimester of
      pregnancy by multivariate analysis of covariance adjusted for age, body mass
      index, family history of hypertension and smoking habits. The magnitudes of the
      white-coat effect for systolic BP in the first, second and third trimesters were
      4.1+/-9.8, 3.4+/-7.1 and 1.8+/-6.0 mm Hg, respectively and those for diastolic BP
      were 3.8+/-7.4, 1.6+/-5.8 and 2.4+/-4.9 mm Hg, respectively. Parity was
      significantly and negatively associated with the white-coat effect for systolic
      BP in the first trimester of pregnancy (nulliparous women: 5.07+/-0.61 mm Hg and
      multiparous women: 2.78+/-0.74 mm Hg, P=0.02) as well as for diastolic BP in the
      second and third trimesters of pregnancy. Age, body mass index, family history of
      hypertension and smoking were not significantly associated with the white-coat
      effect in any trimester of pregnancy. Parity may have an influence on the white
      coat effect in pregnancy; however, the observed effect, on average 1-2 mm Hg, was
      small.

PMID- 26311166
TI  - Morning hypertension and night non-dipping in patients with diabetes and chronic
      kidney disease.
AB  - Morning hypertension (HTN) and nocturnal non-dipping (ND) are closely associated
      with target organ damage and cardiovascular events. However, their importance in
      diabetics with advanced renal disease is unclear. We evaluated the relationships
      of morning HTN and ND with estimated glomerular filtration rate (eGFR) and
      proteinuria, and determined the risk of morning HTN and ND according to presence
      of diabetes mellitus (DM) and chronic kidney disease (CKD) stage. A total of 1312
      patients, including 439 with diabetes, were prospectively recruited at 21 centers
      in Korea. All patients had HTN and an eGFR of 15-89 ml min(-1) per 1.73 m(2).
      Ambulatory 24-h blood pressure was assessed. The rates of morning HTN (25.2% vs.
      13.6%, P<0.001) and ND (58.2% vs. 48.2%, P=0.002) were higher in diabetics than
      in non-diabetics. eGFR was correlated with ND in all patients (P<0.05) and with
      morning HTN only in non-diabetics (P=0.005). Proteinuria was related to ND in all
      patients (P<0.05) and to morning HTN only in diabetics (P=0.001). In a regression
      analysis, the risk of morning HTN was 2.093 (95% confidence interval (95% CI):
      1.070-4.094) for the DMCKD2 group, 1.634 (95% CI: 1.044-2.557) for the CKD3-4
      only group and 2.236 (95% CI: 1.401-3.570) for the DMCKD3-4 group compared with
      the CKD2-only group. The risk of ND was high for stage 3-4 CKD: 1.581 (95% CI:
      1.180-2.120) for non-diabetics and 1.842 (95% CI: 1.348-2.601) for diabetics.
      Diabetics showed higher rates of morning HTN, ND and uncontrolled sustained HTN
      compared with non-diabetics with CKD of the same stages. 

PMID- 26311167
TI  - Transcriptome profiling during a natural host-parasite interaction.
AB  - BACKGROUND: Infection outcome in some coevolving host-pathogens is characterised
      by host-pathogen genetic interactions, where particular host genotypes are
      susceptible only to a subset of pathogen genotypes. To identify candidate genes
      responsible for the infection status of the host, we exposed a Daphnia magna host
      genotype to two bacterial strains of Pasteuria ramosa, one of which results in
      infection, while the other does not. At three time points (four, eight and 12 h)
      post pathogen exposure, we sequenced the complete transcriptome of the hosts
      using RNA-Seq (Illumina). RESULTS: We observed a rapid and transient response to
      pathogen treatment. Specifically, at the four-hour time point, eight genes were
      differentially expressed. At the eight-hour time point, a single gene was
      differentially expressed in the resistant combination only, and no genes were
      differentially expressed at the 12-h time point. CONCLUSIONS: We found that
      pathogen-associated transcriptional activity is greatest soon after exposure.
      Genome-wide resistant combinations were more likely to show upregulation of
      genes, while susceptible combinations were more likely to be downregulated,
      relative to controls. Our results also provide several novel candidate genes that
      may play a pivotal role in determining infection outcomes.

PMID- 26311168
TI  - Donghicola tyrosinivorans sp. nov., a tyrosine-degrading bacterium isolated from
      seawater.
AB  - A Gram-stain-negative, non-motile, aerobic bacterium, strain 13-93-B1T, was
      isolated from seawater off Jeju Island, Republic of Korea, and was subjected to
      polyphasic taxonomic study. Cells formed ivory colonies and were ovoid to rod
      shaped. The strain was catalase-positive, oxidase-negative and grew optimally at
      30  degrees C, in the presence of 1-2 % (w/v) NaCl and at pH 7.0-7.5. It did not
      synthesize bacteriochlorophyll a. Neighbour-joining, maximum-likelihood and
      maximum-parsimony phylogenetic trees based on 16S rRNA gene sequences revealed
      that strain 13-93-B1T clustered with the type strain Donghicola eburneus SW-277T
      (97.0 % 16S rRNA gene sequence similarity). DNA-DNA hybridization between strain
      13-93-B1T and D. eburneus KCTC 12735T was 33.1 +/- 1.4 % (35.2 +/- 2.8 % in a
      reciprocal experiment). The predominant cellular fatty acid was summed feature 8
      (C18 : 1omega7c/C18 : 1omega6c; 76.9 %). The major respiratory quinone was
      ubiquinone Q-10 and polar lipids detected in strain 13-93-B1T were
      phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, an
      unidentified aminolipid and unidentified lipids. The DNA G+C content of strain 13
      93-B1T was 60.4 mol%. Based on the phenotypic, chemotaxonomic and phylogenetic
      data presented, strain 13-93-B1T is considered to represent a novel species of
      the genus Donghicola, for which the name Donghicola tyrosinivorans sp. nov. is
      proposed. The type strain is 13-93-B1T ( = DSM 100212T = KCTC 42571T).

PMID- 26311169
TI  - Association Between Visuospatial Ability and Vestibular Function in the Baltimore
      Longitudinal Study of Aging.
AB  - OBJECTIVES: To investigate the relationship between vestibular loss associated
      with aging and age-related decline in visuospatial function. DESIGN: Cross
      sectional analysis within a prospective cohort study. SETTING: Baltimore
      Longitudinal Study of Aging (BLSA). PARTICIPANTS: Community-dwelling BLSA
      participants with a mean age of 72 (range 26-91) (N = 183). MEASUREMENTS:
      Vestibular function was measured using vestibular-evoked myogenic potentials.
      Visuospatial cognitive tests included Card Rotations, Purdue Pegboard, Benton
      Visual Retention Test, and Trail-Making Test Parts A and B. Tests of executive
      function, memory, and attention were also considered. RESULTS: Participants
      underwent vestibular and cognitive function testing. In multiple linear
      regression analyses, poorer vestibular function was associated with poorer
      performance on Card Rotations (P = .001), Purdue Pegboard (P = .005), Benton
      Visual Retention Test (P = 0.008), and Trail-Making Test Part B (P = .04).
      Performance on tests of executive function and verbal memory were not
      significantly associated with vestibular function. Exploratory factor analyses in
      a subgroup of participants who underwent all cognitive tests identified three
      latent cognitive abilities: visuospatial ability, verbal memory, and working
      memory and attention. Vestibular loss was significantly associated with lower
      visuospatial and working memory and attention factor scores. CONCLUSION:
      Significant consistent associations between vestibular function and tests of
      visuospatial ability were observed in a sample of community-dwelling adults.
      Impairment in visuospatial skills is often one of the first signs of dementia and
      Alzheimer's disease. Further longitudinal studies are needed to evaluate whether
      the relationship between vestibular function and visuospatial ability is causal.

PMID- 26311170
TI  - Oxidative stress associated with pathological lesions in the liver of rats
      experimentally infected by Fasciola hepatica.
AB  - The aim of this study was to analyze the antioxidant status and oxidative profile
      in serum and liver of rats experimentally infected with Fasciola hepatica and its
      relationship with pathological findings. Twenty-four rats were divided into two
      groups: group A consisted of 12 healthy rats and group B of 12 rats infected
      orally with 20 metacercaria of F. hepatica. At days 20 and 150 post-infection
      (PI), blood and liver samples of six animals from each group were collected. The
      protein oxidation (AOPP technique: advanced oxidation protein products) and
      antioxidants (FRAP technique: ferric reducing antioxidant power) levels were
      measured in serum and liver. Furthermore, nitrite/nitrate (NOx) levels and lipid
      peroxidation (TBARS technique: thiobarbituric acid reactive substances) were
      measured in liver. AOPP and FRAP levels were increased (P < 0.05) in serum and
      liver of infected animals in acute and chronic infection when compared with
      healthy animals. The same occurred with TBARS and NOx levels in the liver (P <
      0.05). Histopathology revealed periportal fibrous hepatitis, composed of an
      abundant inflammatory infiltrate in portal spaces on infected animals, as well as
      bile duct hyperplasia. The results found seem to be related to the host free
      radical production demonstrated in serum samples and liver due to the parasite
      infection. 

PMID- 26311171
TI  - Effect of thiram and of a hydrocarbon mixture on freshwater macroinvertebrate
      communities in outdoor stream and pond mesocosms: II. Biological and ecological
      trait responses and leaf litter breakdown.
AB  - Higher-tier ecological risk assessment of chemicals often relies upon studies in
      dynamic and/or static mesocosms. Physico-chemical and hydrological properties of
      each type of mesocosm result in specific chemicals fate, community functioning,
      and potential recovery. In the present study, macroinvertebrate abundance- and
      biomass-weighted biological and ecological trait matrices were used to assess the
      effects of a dithiocarbamate fungicide, thiram (35 and 170 ug l(-1)), and of a
      petroleum middle distillate (0.01, 0.4, 2 and 20 mg l(-1)) in outdoor stream and
      pond mesocosms. Trait sensitivity was characterized using functional diversity
      indices and trait modality distributions to assess the influence of the type of
      experimental systems and the ability of traits to disentangle chemical-induced
      effects from temporal and stochastic variations. In addition, leaf litter
      breakdown was used as an integrative functional endpoint. Regardless to the
      substance, treatments had a direct effect on the functional structure of benthic
      macroinvertebrate communities in streams but not in ponds, suggesting that global
      functional responses to chemicals are system-specific. Although both substances
      had an effect in streams, differences were noticed in the nature of the affected
      traits suggesting that chemical mode of action plays a role in functional
      alterations. This was illustrated by the link between negative effects of
      chemical exposure on detritivorous taxa and reduced litter breakdown rate in
      streams. Therefore, characterisation of macroinvertebrate biological traits
      associated with the measurement of a functional process such as litter breakdown
      may provide a comprehensive understanding of the effects occurring in mesocosms
      exposed to organic chemicals.

PMID- 26311172
TI  - N-Methylpyrrolidone Hydroperoxide/Cs2 CO3 as an Excellent Reagent System for the
      Hydroxy-Directed Diastereoselective Epoxidation of Electron-Deficient Olefins.
AB  - This report introduces N-methylpyrrolidone hydroperoxide (NMPOOH)/base as an
      excellent reagent system for hydroxy-directed syn selective epoxidation of
      electron-deficient olefins, characterized by high diastereoselectivity, short
      reaction times and remarkable chemoselectivity, especially in presence of
      oxidatively labile nitrogen or sulfur atoms. NMPOOH also proves efficient in the
      oxidation of electron-deficient aromatic aldehydes, in the removal of
      oxazolidinone chiral auxiliary, and in the functionalization of alkenes and
      alkynes, showing wide application potential. 

PMID- 26311173
TI  - The metabolism of (R)-3-hydroxybutyrate is regulated by the enhancer-binding
      protein PA2005 and the alternative sigma factor RpoN in Pseudomonas aeruginosa
      PAO1.
AB  - A variety of soil-dwelling bacteria produce polyhydroxybutyrate (PHB), which
      serves as a source of energy and carbon under nutrient deprivation. Bacteria
      belonging to the genus Pseudomonas do not generally produce PHB but are capable
      of using the PHB degradation product (R)-3-hydroxybutyrate [(R)-3-HB] as a growth
      substrate. Essential to this utilization is the NAD+-dependent dehydrogenase BdhA
      that converts (R)-3-HB into acetoacetate, a molecule that readily enters central
      metabolism. Apart from the numerous studies that had focused on the biochemical
      characterization of BdhA, there was nothing known about the assimilation of (R)-3
      HB in Pseudomonas, including the genetic regulation of bdhA expression. This
      study aimed to define the regulatory factors that govern or dictate the
      expression of the bdhA gene and (R)-3-HB assimilation in Pseudomonas aeruginosa
      PAO1. Importantly, expression of the bdhA gene was found to be specifically
      induced by (R)-3-HB in a manner dependent on the alternative sigma factor RpoN
      and the enhancer-binding protein PA2005.This mode of regulation was essential for
      the utilization of (R)-3-HB as a sole source of energy and carbon. However, non
      induced levels of bdhA expression were sufficient for P. aeruginosa PAO1 to grow
      on ( +/- )-1,3-butanediol, which is catabolized through an (R)-3-HB intermediate.
      Because this is, we believe, the first report of an enhancer-binding protein that
      responds to (R)-3-HB, PA2005 was named HbcR for (R)-3-hydroxybutyrate catabolism
      regulator. 

PMID- 26311174
TI  - Detection of satellite cells during skeletal muscle wound healing in rats: time
      dependent expressions of Pax7 and MyoD in relation to wound age.
AB  - The study was focused on time-dependent expressions of paired-box transcription
      factor 7 (Pax7) and myoblast determination protein (MyoD) during skeletal muscle
      wound healing. An animal model of skeletal muscle contusion was established in 40
      Sprague-Dawley male rats. Samples were taken at 1, 3, 5, 7, 9, 13, 17, and 21
      days after injury, respectively (five rats in each posttraumatic interval). Five
      rats were employed as control. By morphometric analysis, the data based on the
      number of Pax7(+)/MyoD(-), Pax7(+)/MyoD(+), and Pax7(-)/MyoD(+) cells were highly
      correlated with the wound age. Pax7 and MyoD expressions were upregulated after
      injury by Western blot and quantitative real-time PCR assays. The relative
      quantity of Pax7 protein peaked at 5 days after injury, which was >1.13, and
      decreased thereafter. Similarly, the relative quantity of MyoD mRNA expression
      peaked at 3 days after injury, which was >2.59. The relative quantity of Pax7
      protein >0.73 or mRNA expression >2.38 or the relative quantity of MyoD protein
      >1.33 suggested a wound age of 3 to 7 days. The relative quantity of MyoD mRNA
      expression >2.02 suggested a wound age of 1 to 7 days post-injury. In conclusion,
      the expressions of Pax7 and MyoD are upregulated in a time-dependent manner
      during skeletal muscle wound healing, suggesting that Pax7 and MyoD may be
      potential markers for wound age estimation in skeletal muscle.

PMID- 26311175
TI  - The Influence of Biomedical Information and Childhood History on Sentencing.
AB  - A recent trend in court is for defense attorneys to introduce brain scans and
      other forms of biomedical information (BI) into criminal trials as mitigating
      evidence. The present study investigates how BI, when considered in combination
      with a defendant's childhood information (CI), can influence the length of a
      defendant's sentence. We hypothesized that certain combinations of BI and CI
      result in shorter sentences because they suggest that the defendant poses less of
      a threat to society. Participants were asked to read accounts of the trial of a
      murder suspect and, based on the information therein, recommend a sentence as if
      they were the judge. The defendant was diagnosed with psychopathy, but biomedical
      information regarding that diagnosis was included or excluded depending on the BI
      condition. The defendant was further described as growing up in either a loving
      or abusive family. The results showed that, if BI was present in the trial
      account, the defendant from an abusive family was perceived as less of a threat
      to society and received a shorter recommended sentence than if the defendant had
      been from a loving family. If BI was absent from the account, the pattern was
      reversed: the defendant from a loving family was perceived as less of a threat to
      society and received a shorter recommended sentence than if he had been from an
      abusive family. Implications for the use of BI and CI in court trials are
      discussed, as well as their relationship to free will and the function of
      punishment as retribution and utility.

PMID- 26311176
TI  - An Exploration into Fern Genome Space.
AB  - Ferns are one of the few remaining major clades of land plants for which a
      complete genome sequence is lacking. Knowledge of genome space in ferns will
      enable broad-scale comparative analyses of land plant genes and genomes, provide
      insights into genome evolution across green plants, and shed light on genetic and
      genomic features that characterize ferns, such as their high chromosome numbers
      and large genome sizes. As part of an initial exploration into fern genome space,
      we used a whole genome shotgun sequencing approach to obtain low-density coverage
      (~0.4X to 2X) for six fern species from the Polypodiales (Ceratopteris,
      Pteridium, Polypodium, Cystopteris), Cyatheales (Plagiogyria), and Gleicheniales
      (Dipteris). We explore these data to characterize the proportion of the nuclear
      genome represented by repetitive sequences (including DNA transposons,
      retrotransposons, ribosomal DNA, and simple repeats) and protein-coding genes,
      and to extract chloroplast and mitochondrial genome sequences. Such initial
      sweeps of fern genomes can provide information useful for selecting a promising
      candidate fern species for whole genome sequencing. We also describe variation of
      genomic traits across our sample and highlight some differences and similarities
      in repeat structure between ferns and seed plants. 

PMID- 26311177
TI  - Enzyme engineering in biomimetic compartments.
AB  - The success of a directed evolution approach to creating custom-made enzymes
      relies in no small part on screening as many clones as possible. The
      miniaturisation of assays into pico to femtoliter compartments (emulsion
      droplets, vesicles or gel-shell beads) makes directed evolution campaigns
      practically more straightforward than current large scale industrial screening
      that requires liquid handling equipment and much manpower. Several recent
      experimental formats have established protocols to screen more than 10 million
      compartments per day, representing unprecedented throughput at low cost. This
      review introduces the emerging approaches towards making biomimetic man-made
      compartments that are poised to be adapted by a wider circle of researchers. In
      addition to cost and time saving, control of selection pressures and conditions,
      the quantitative readout that reports on every library members and the ability to
      develop strategies based on these data will increase the degrees of freedom in
      designing and testing strategies for directed evolution experiments. 

PMID- 26311178
TI  - Emergence of invariant representation of vocalizations in the auditory cortex.
AB  - An essential task of the auditory system is to discriminate between different
      communication signals, such as vocalizations. In everyday acoustic environments,
      the auditory system needs to be capable of performing the discrimination under
      different acoustic distortions of vocalizations. To achieve this, the auditory
      system is thought to build a representation of vocalizations that is invariant to
      their basic acoustic transformations. The mechanism by which neuronal populations
      create such an invariant representation within the auditory cortex is only
      beginning to be understood. We recorded the responses of populations of neurons
      in the primary and nonprimary auditory cortex of rats to original and
      acoustically distorted vocalizations. We found that populations of neurons in the
      nonprimary auditory cortex exhibited greater invariance in encoding vocalizations
      over acoustic transformations than neuronal populations in the primary auditory
      cortex. These findings are consistent with the hypothesis that invariant
      representations are created gradually through hierarchical transformation within
      the auditory pathway. 

PMID- 26311179
TI  - Modulation of error-sensitivity during a prism adaptation task in people with
      cerebellar degeneration.
AB  - Cerebellar damage can profoundly impair human motor adaptation. For example, if
      reaching movements are perturbed abruptly, cerebellar damage impairs the ability
      to learn from the perturbation-induced errors. Interestingly, if the perturbation
      is imposed gradually over many trials, people with cerebellar damage may exhibit
      improved adaptation. However, this result is controversial, since the
      differential effects of gradual vs. abrupt protocols have not been observed in
      all studies. To examine this question, we recruited patients with pure cerebellar
      ataxia due to cerebellar cortical atrophy (n = 13) and asked them to reach to a
      target while viewing the scene through wedge prisms. The prisms were computer
      controlled, making it possible to impose the full perturbation abruptly in one
      trial, or build up the perturbation gradually over many trials. To control visual
      feedback, we employed shutter glasses that removed visual feedback during the
      reach, allowing us to measure trial-by-trial learning from error (termed error
      sensitivity), and trial-by-trial decay of motor memory (termed forgetting). We
      found that the patients benefited significantly from the gradual protocol,
      improving their performance with respect to the abrupt protocol by exhibiting
      smaller errors during the exposure block, and producing larger aftereffects
      during the postexposure block. Trial-by-trial analysis suggested that this
      improvement was due to increased error-sensitivity in the gradual protocol.
      Therefore, cerebellar patients exhibited an improved ability to learn from error
      if they experienced those errors gradually. This improvement coincided with
      increased error-sensitivity and was present in both groups of subjects,
      suggesting that control of error-sensitivity may be spared despite cerebellar
      damage. 

PMID- 26311180
TI  - Interactions between target location and reward size modulate the rate of
      microsaccades in monkeys.
AB  - We have studied how rewards modulate the occurrence of microsaccades by
      manipulating the size of an expected reward and the location of the cue that sets
      the expectations for future reward. We found an interaction between the size of
      the reward and the location of the cue. When monkeys fixated on a cue that
      signaled the size of future reward, the frequency of microsaccades was higher if
      the monkey expected a large vs. a small reward. When the cue was presented at a
      site in the visual field that was remote from the position of fixation, reward
      size had the opposite effect: the frequency of microsaccades was lower when the
      monkey was expecting a large reward. The strength of pursuit initiation also was
      affected by reward size and by the presence of microsaccades just before the
      onset of target motion. The gain of pursuit initiation increased with reward size
      and decreased when microsaccades occurred just before or after the onset of
      target motion. The effect of the reward size on pursuit initiation was much
      larger than any indirect effects reward might cause through modulation of the
      rate of microsaccades. We found only a weak relationship between microsaccade
      direction and the location of the exogenous cue relative to fixation position,
      even in experiments where the location of the cue indicated the direction of
      target motion. Our results indicate that the expectation of reward is a powerful
      modulator of the occurrence of microsaccades, perhaps through attentional
      mechanisms. 

PMID- 26311181
TI  - A positive feedback at the cellular level promotes robustness and modulation at
      the circuit level.
AB  - This article highlights the role of a positive feedback gating mechanism at the
      cellular level in the robustness and modulation properties of rhythmic activities
      at the circuit level. The results are presented in the context of half-center
      oscillators, which are simple rhythmic circuits composed of two reciprocally
      connected inhibitory neuronal populations. Specifically, we focus on rhythms that
      rely on a particular excitability property, the postinhibitory rebound, an
      intrinsic cellular property that elicits transient membrane depolarization when
      released from hyperpolarization. Two distinct ionic currents can evoke this
      transient depolarization: a hyperpolarization-activated cation current and a low
      threshold T-type calcium current. The presence of a slow activation is specific
      to the T-type calcium current and provides a slow positive feedback at the
      cellular level that is absent in the cation current. We show that this slow
      positive feedback is required to endow the network rhythm with physiological
      modulation and robustness properties. This study thereby identifies an essential
      cellular property to be retained at the network level in modeling network
      robustness and modulation. 

PMID- 26311182
TI  - Self-selected conscious strategies do not modulate motor cortical output during
      action observation.
AB  - The human motor system is active not only when actions are performed but also
      when they are observed. Experimenters often manipulate aspects of the action or
      context to examine factors that influence this "mirror" response. However, little
      is known about the role of the observer's own top-down intentions and motivation.
      In this exploratory study, we investigated whether observers are able to exert
      conscious control over their mirror response, when they are explicitly instructed
      to either increase or decrease mirroring. Transcranial magnetic stimulation (TMS)
      was used to elicit motor-evoked potentials (MEPs) in a thumb abductor muscle as
      participants (n = 13) watched a video of a hand squeezing a rubber ball. The size
      of these MEPs, relative to the size of MEPs elicited during fixation cross
      observation, was taken as an index of mirroring. In an initial block of trials,
      participants were instructed to merely observe the actions presented. After the
      first block, the concept of mirroring was explained to the participants, and in
      the second and third blocks participants were instructed to either increase or
      decrease their mirror response. We did not instruct them about how to achieve
      this increase or decrease. Our results showed no difference in either
      facilitation or absolute motor excitability (i.e., nonnormalized MEP size)
      between the three blocks, indicating that individuals do not seem to be able to
      exert control over motor excitability during action observation, at least in the
      absence of a specific and maintained strategy. 

PMID- 26311183
TI  - Morphology and function of three VIP-expressing amacrine cell types in the mouse
      retina.
AB  - Amacrine cells (ACs) are the most diverse class of neurons in the retina. The
      variety of signals provided by ACs allows the retina to encode a wide range of
      visual features. Of the 30-50 AC types in mammalian species, few have been
      studied in detail. Here, we combine genetic and viral strategies to identify and
      to characterize morphologically three vasoactive intestinal polypeptide
      expressing GABAergic AC types (VIP1-, VIP2-, and VIP3-ACs) in mice. Somata of
      VIP1- and VIP2-ACs reside in the inner nuclear layer and somata of VIP3-ACs in
      the ganglion cell layer, and they show asymmetric distributions along the
      dorsoventral axis of the retina. Neurite arbors of VIP-ACs differ in size (VIP1
      ACs ~ VIP3-ACs > VIP2-ACs) and stratify in distinct sublaminae of the inner
      plexiform layer. To analyze light responses and underlying synaptic inputs, we
      target VIP-ACs under 2-photon guidance for patch-clamp recordings. VIP1-ACs
      depolarize strongly to light increments (ON) over a wide range of stimulus sizes
      but show size-selective responses to light decrements (OFF), depolarizing to
      small and hyperpolarizing to large stimuli. The switch in polarity of OFF
      responses is caused by pre- and postsynaptic surround inhibition. VIP2- and VIP3
      ACs both show small depolarizations to ON stimuli and large hyperpolarizations to
      OFF stimuli but differ in their spatial response profiles. Depolarizations are
      caused by ON excitation outweighing ON inhibition, whereas hyperpolarizations
      result from pre- and postsynaptic OFF-ON crossover inhibition. VIP1-, VIP2-, and
      VIP3-ACs thus differ in response polarity and spatial tuning and contribute to
      the diversity of inhibitory and neuromodulatory signals in the retina. 

PMID- 26311184
TI  - Predictive coding in autism spectrum disorder and attention deficit hyperactivity
      disorder.
AB  - Predictive coding has been proposed as a framework to understand neural processes
      in neuropsychiatric disorders. We used this approach to describe mechanisms
      responsible for attentional abnormalities in autism spectrum disorder (ASD) and
      attention deficit hyperactivity disorder (ADHD). We monitored brain dynamics of
      59 children (8-15 yr old) who had ASD or ADHD or who were control participants
      via high-density electroencephalography. We performed analysis at the scalp and
      source-space levels while participants listened to standard and deviant tone
      sequences. Through task instructions, we manipulated top-down expectation by
      presenting expected and unexpected deviant sequences. Children with ASD showed
      reduced superior frontal cortex (FC) responses to unexpected events but increased
      dorsolateral prefrontal cortex (PFC) activation to expected events. In contrast,
      children with ADHD exhibited reduced cortical responses in superior FC to
      expected events but strong PFC activation to unexpected events. Moreover, neural
      abnormalities were associated with specific control mechanisms, namely,
      inhibitory control in ASD and set-shifting in ADHD. Based on the predictive
      coding account, top-down expectation abnormalities could be attributed to a
      disproportionate reliance (precision) allocated to prior beliefs in ASD and to
      sensory input in ADHD. 

PMID- 26311185
TI  - Adenosine-mediated modulation of ventral horn interneurons and spinal motoneurons
      in neonatal mice.
AB  - Neuromodulation allows neural networks to adapt to varying environmental and
      biomechanical demands. Purinergic signaling is known to be an important
      modulatory system in many parts of the CNS, including motor control circuitry. We
      have recently shown that adenosine modulates the output of mammalian spinal
      locomotor control circuitry (Witts EC, Panetta KM, Miles GB. J Neurophysiol 107:
      1925-1934, 2012). Here we investigated the cellular mechanisms underlying this
      adenosine-mediated modulation. Whole cell patch-clamp recordings were performed
      on ventral horn interneurons and motoneurons within in vitro mouse spinal cord
      slice preparations. We found that adenosine hyperpolarized interneurons and
      reduced the frequency and amplitude of synaptic inputs to interneurons. Both
      effects were blocked by the A1-type adenosine receptor antagonist DPCPX. Analysis
      of miniature postsynaptic currents recorded from interneurons revealed that
      adenosine reduced their frequency but not amplitude, suggesting that adenosine
      acts on presynaptic receptors to modulate synaptic transmission. In contrast to
      interneurons, recordings from motoneurons revealed an adenosine-mediated
      depolarization. The frequency and amplitude of synaptic inputs to motoneurons
      were again reduced by adenosine, but we saw no effect on miniature postsynaptic
      currents. Again these effects on motoneurons were blocked by DPCPX. Taken
      together, these results demonstrate differential effects of adenosine, acting via
      A1 receptors, in the mouse spinal cord. Adenosine has a general inhibitory action
      on ventral horn interneurons while potentially maintaining motoneuron
      excitability. This may allow for adaptation of the locomotor pattern generated by
      interneuronal networks while helping to ensure the maintenance of overall motor
      output. 

PMID- 26311186
TI  - Predicting plasticity: acute context-dependent changes to vocal performance
      predict long-term age-dependent changes.
AB  - Understanding the factors that predict and guide variation in behavioral change
      can lend insight into mechanisms of motor plasticity and individual differences
      in behavior. The performance of adult birdsong changes with age in a manner that
      is similar to rapid context-dependent changes to song. To reveal mechanisms of
      vocal plasticity, we analyzed the degree to which variation in the direction and
      magnitude of age-dependent changes to Bengalese finch song could be predicted by
      variation in context-dependent changes. Using a repeated-measures design, we
      found that variation in age-dependent changes to the timing, sequencing, and
      structure of vocal elements ("syllables") was significantly predicted by
      variation in context-dependent changes. In particular, the degree to which the
      duration of intersyllable gaps, syllable sequencing at branch points, and
      fundamental frequency of syllables within spontaneous [undirected (UD)] songs
      changed over time was correlated with the degree to which these features changed
      from UD song to female-directed (FD) song in young-adult finches (FDyoung). As
      such, the structure of some temporal features of UD songs converged over time
      onto the structure of FDyoung songs. This convergence suggested that the FDyoung
      song could serve as a stable target for vocal motor plasticity. Consequently, we
      analyzed the stability of FD song and found that the temporal structure of FD
      song changed significantly over time in a manner similar to UD song. Because FD
      song is considered a state of heightened performance, these data suggest that age
      dependent changes could reflect practice-related improvements in vocal motor
      performance. 

PMID- 26311187
TI  - Intradermal endothelin-1 excites bombesin-responsive superficial dorsal horn
      neurons in the mouse.
AB  - Endothelin-1 (ET-1) has been implicated in nonhistaminergic itch. Here we used
      electrophysiological methods to investigate whether mouse superficial dorsal horn
      neurons respond to intradermal (id) injection of ET-1 and whether ET-1-sensitive
      neurons additionally respond to other pruritic and algesic stimuli or spinal
      superfusion of bombesin, a homolog of gastrin-releasing peptide (GRP) that
      excites spinal itch-signaling neurons. Single-unit recordings were made from
      lumbar dorsal horn neurons in pentobarbital-anesthetized C57BL/6 mice. We
      searched for units that exhibited elevated firing after id injection of ET-1 (1
      MUg/MUl). Responsive units were further tested with mechanical stimuli, bombesin
      (spinal superfusion, 200 MUg.ml(-1).min(-1)), heating, cooling, and additional
      chemicals [histamine, chloroquine, allyl isothiocyanate (AITC), capsaicin]. Of 40
      ET-1-responsive units, 48% responded to brush and pinch [wide dynamic range
      (WDR)] and 52% to pinch only [high threshold (HT)]. Ninety-three percent
      responded to noxious heat, 50% to cooling, and >70% to histamine, chloroquine,
      AITC, and capsaicin. Fifty-seven percent responded to bombesin, suggesting that
      they participate in spinal itch transmission. That most ET-1-sensitive spinal
      neurons also responded to pruritic and algesic stimuli is consistent with
      previous studies of pruritogen-responsive dorsal horn neurons. We previously
      hypothesized that pruritogen-sensitive neurons signal itch. The observation that
      ET-1 activates nociceptive neurons suggests that both itch and pain signals may
      be generated by ET-1 to result in simultaneous sensations of itch and pain,
      consistent with observations that ET-1 elicits both itch- and pain-related
      behaviors in animals and burning itch sensations in humans. 

PMID- 26311190
TI  - Effect of drought stress on the development of endosperm starch granules and the
      composition and physicochemical properties of starches from soft and hard wheat.
AB  - BACKGROUND: The objectives of this study were to: (1) observe the effects of
      drought stress (DS) on the structural development of endosperm starch granules;
      (2) investigate the effects of DS on composition and physicochemical properties
      of starches; and (3) compare the different responses to DS between soft and hard
      wheat. RESULTS: DS resulted in large A-type starch granules at 12 d after
      anthesis (DAA) and a high percentage of B-type starch granules at 18 DAA in
      endosperm cells of the two wheat cultivars. DS decreased the 1000-grain weight,
      total starch and amylose contents, and amylose-to-amylopectin ratio of both
      starches. DS also decreased the percentage of B-type starch granules in NM13 and
      increased the number of hollows on the surface of A-type starch granules in XM33.
      DS further increased the swelling power and affected pasting properties of both
      starches. DS also significantly enhanced the hydrolysis degrees of starches by
      pancreatic alpha-amylase, Aspergillus niger amyloglucosidase, and HCl in NM13. DS
      altered the contents of rapidly digestible, slowly digestible, and resistant
      starches in native, gelatinised, and retrograded starches. CONCLUSION: Overall,
      DS can affect the development of endosperm starch granules and the
      physicochemical properties of starches, thus affecting the qualities of the final
      wheat products. (c) 2015 Society of Chemical Industry.

PMID- 26311188
TI  - Imaging fictive locomotor patterns in larval Drosophila.
AB  - We have established a preparation in larval Drosophila to monitor fictive
      locomotion simultaneously across abdominal and thoracic segments of the isolated
      CNS with genetically encoded Ca(2+) indicators. The Ca(2+) signals closely
      followed spiking activity measured electrophysiologically in nerve roots. Three
      motor patterns are analyzed. Two comprise waves of Ca(2+) signals that progress
      along the longitudinal body axis in a posterior-to-anterior or anterior-to
      posterior direction. These waves had statistically indistinguishable
      intersegmental phase delays compared with segmental contractions during forward
      and backward crawling behavior, despite being ~10 times slower. During these
      waves, motor neurons of the dorsal longitudinal and transverse muscles were
      active in the same order as the muscle groups are recruited during crawling
      behavior. A third fictive motor pattern exhibits a left-right asymmetry across
      segments and bears similarities with turning behavior in intact larvae, occurring
      equally frequently and involving asymmetry in the same segments. Ablation of the
      segments in which forward and backward waves of Ca(2+) signals were normally
      initiated did not eliminate production of Ca(2+) waves. When the brain and
      subesophageal ganglion (SOG) were removed, the remaining ganglia retained the
      ability to produce both forward and backward waves of motor activity, although
      the speed and frequency of waves changed. Bilateral asymmetry of activity was
      reduced when the brain was removed and abolished when the SOG was removed. This
      work paves the way to studying the neural and genetic underpinnings of
      segmentally coordinated motor pattern generation in Drosophila with imaging
      techniques. 

PMID- 26311189
TI  - Normalization in human somatosensory cortex.
AB  - Functional magnetic resonance imaging (fMRI) was used to measure activity in
      human somatosensory cortex and to test for cross-digit suppression. Subjects
      received stimulation (vibration of varying amplitudes) to the right thumb
      (target) with or without concurrent stimulation of the right middle finger
      (mask). Subjects were less sensitive to target stimulation (psychophysical
      detection thresholds were higher) when target and mask digits were stimulated
      concurrently compared with when the target was stimulated in isolation. fMRI
      voxels in a region of the left postcentral gyrus each responded when either digit
      was stimulated. A regression model (called a forward model) was used to separate
      the fMRI measurements from these voxels into two hypothetical channels, each of
      which responded selectively to only one of the two digits. For the channel tuned
      to the target digit, responses in the left postcentral gyrus increased with
      target stimulus amplitude but were suppressed by concurrent stimulation to the
      mask digit, evident as a shift in the gain of the response functions. For the
      channel tuned to the mask digit, a constant baseline response was evoked for all
      target amplitudes when the mask was absent and responses decreased with
      increasing target amplitude when the mask was concurrently presented. A
      computational model based on divisive normalization provided a good fit to the
      measurements for both mask-absent and target + mask stimulation. We conclude that
      the normalization model can explain cross-digit suppression in human
      somatosensory cortex, supporting the hypothesis that normalization is a canonical
      neural computation. 

PMID- 26311192
TI  - Mechanisms of change during group metacognitive therapy for repetitive negative
      thinking in primary and non-primary generalized anxiety disorder.
AB  - Repetitive negative thinking (RNT) is a transdiagnostic process that serves to
      maintain emotional disorders. Metacognitive theory suggests that positive and
      negative metacognitive beliefs guide the selection of RNT as a coping strategy
      which, in turn, increases psychological distress. The aim of this study was to
      test the indirect effect of metacognitive beliefs on psychological distress via
      RNT. Patients (N=52) with primary and non-primary generalized anxiety disorder
      attended a brief, six-week group metacognitive therapy program and completed
      measures of metacognitive beliefs, RNT, and symptoms at the first and final
      treatment sessions, and at a one-month follow-up. Prospective indirect effects
      models found that negative metacognitive beliefs (but not positive metacognitive
      beliefs) had a significant indirect effect on psychological distress via RNT. As
      predicted by metacognitive theory, targeting negative metacognitions in treatment
      appears to reduce RNT and, in turn, emotional distress. Further research using
      alternative measures at multiple time points during therapy is required to
      determine whether the absence of a relationship with positive metacognitive
      beliefs in this study was a consequence of (a) psychometric issues, (b) these
      beliefs only being relevant to a subgroup of patients, or (c) a lack of awareness
      early in treatment. 

PMID- 26311191
TI  - The Relationship Between Psychological Distress, Negative Cognitions, and
      Expectancies on Problem Drinking: Exploring a Growing Problem Among University
      Students.
AB  - Few studies have sought to understand the concurrent relationship between
      cognitive and affective processes on alcohol use and negative alcohol-related
      consequences, despite both being identified as predictive risk factors in the
      college population. More research is needed to understand the relationships
      between identified factors of problem drinking among this at-risk population. The
      purpose of this study was to test if the relationship between psychological
      distress and problem drinking among university students (N = 284; M-age = 19.77)
      was mediated by negative affect regulation strategies and positive alcohol
      related expectancies. Two latent mediation models of problem drinking were tested
      using structural equation modeling (SEM). The parsimonious three-path mediated
      latent model was supported by the data, as evidenced by several model fit
      indices. Furthermore, the alternate saturated model provided similar fit to the
      data, but contained several direct relationships that were not statistically
      significant. The relationship between psychological distress and problem drinking
      was mediated by an extended contributory chain, including negative affect
      regulation and positive alcohol-related expectancies. Implications for prevention
      and treatment, as well as future directions, are discussed. 

PMID- 26311193
TI  - Self-reported hearing loss and manual audiometry: A rural versus urban
      comparison.
AB  - OBJECTIVE: To examine whether self-reported hearing difficulty is an accurate
      measure of hearing loss compared with standard hearing screening with pure tone
      audiometry in rural and urban communities. DESIGN: Convenience sampling. SETTING:
      Urban and rural areas of Western Australia. PARTICIPANTS: A total of 2090
      participants (923 men; 1165 women; 2 unknown) aged 20-100 years presenting for
      community-based hearing screening in urban (982) and rural (1090) areas.
      INTERVENTIONS: Self-reported hearing difficulty assessed with the Hearing
      Handicap Inventory for the Elderly - Screening questionnaire. Hearing loss
      defined as average hearing thresholds >25 dB in the better ear using screening
      audiometry conducted at 500, 1000, 2000 and 4000 Hz. MAIN OUTCOME MEASURES: Nil.
      RESULTS: The Hearing Handicap Inventory for the Elderly - Screening was sensitive
      (>=60 years = 76.69%; <60 years = 71.67%) but not specific (>=60 years = 45.15%;
      <60 years = 49.63%) for identifying hearing loss. The <60 age group had a hearing
      loss prevalence of 25.6%, and a false-positive rate of 67.12% compared with a
      prevalence of 69.12% and false-positive rate of 29.77% for the >=60 age group.
      For all ages, rural participants were more likely to have a disabling hearing
      loss (odds ratio 2.04 (95% confidence interval, 1.55-2.67); chi(2)(1) = 27.28; P
      < 0.001), but there were no significant differences in hearing aid uptake.
      CONCLUSIONS: Patients in rural areas presenting for hearing screenings are more
      likely to suffer hearing loss than adults in urban areas. We suggest rural health
      practitioners incorporate a self-reported hearing loss questionnaire into health
      check-ups for adults, particularly patients aged >=60 years due to the high
      prevalence of hearing loss in this group.

PMID- 26311194
TI  - Impacts of BDE209 addition on Pb uptake, subcellular partitioning and gene
      toxicity in earthworm (Eisenia fetida).
AB  - Lead (Pb) and decabromodiphenyl ether (BDE209) are the mainly co-existed
      contaminants at e-waste recycling sites. The potential toxicity of Pb (250 MUg g(
      1)) to earthworm Eisenia fetida in the presence of BDE209 (1, 10 and 100 MUg g(
      1)) was determined during 14-d incubation period. Compared to Pb treatment alone,
      the co-exposure with 1 MUg g(-1) BDE209 barely affected Pb uptake, subcellular
      partitioning and gene expression; however, histopathological changes in
      earthworms' body wall (epidermal, circular and longitudinal muscles) demonstrated
      that 10 and 100 MUg g(-1) BDE209 additions enhanced Pb uptake and altered its
      subcellular partitioning, indicating that Pb redistributed from fractions E (cell
      debris) and D (metal-rich granules) to fraction C (cytosols); Additionally,
      BDE209 supply significantly inhibited (p<0.05) the induction of SOD (superoxide
      dismutase) and CAT (catalase) gene expressions (maximum down-regulation 59% for
      SOD gene at Pb+100 MUg g(-1) BDE209 and 89% for CAT gene at Pb+10 MUg g(-1)
      BDE209), while facilitated (p<0.05) Hsp90 (heat shock protein 90) gene expression
      with maximum induction rate of 120% after exposure to Pb+10 MUg g(-1) BDE209.
      These findings illustrate the importance of considering environmental BDE209 co
      exposure when assessing Pb bioaccumulation and toxicity in multi-contaminated
      soil ecosystems.

PMID- 26311195
TI  - Transformation of organic matters in animal wastes during composting.
AB  - The transformation of organic matters in swine, cow and chicken manures was
      compared and evaluated using elemental analysis, FTIR, (13)C NMR,
      pyrolysis/GC/MS, Biolog and multiple fluorochrome over 60 days composting. The
      results revealed that cow manure exhibited the greatest C/N and aromaticity,
      whereas chicken manure exhibited the highest nitrogen and sulfur contents. O
      alkyl-C was predominant carbon structure in the three manures. Alkyl-C and
      carboxyl-C were decomposed dramatically in initial 10 days, and mineralization of
      O-alkyl-C dominated the curing stage. During pyrolysis of chicken, cow, and swine
      manures, the majority products were fatty acids, phenols and cholestene
      derivatives, respectively, however, phenols and cholestene derivatives were
      strongly reduced in the mature manures. Furthermore, microorganisms in the raw
      cow, chicken and swine manure demonstrated the highest degradation capabilities
      for carbohydrates, lipids and amino acids, respectively. Spatial differences in
      the contents of solid organics in the manure particles were negligible through
      detection by multiple staining methods during composting. 

PMID- 26311196
TI  - The Relationship Between Self-Compassion and Well-Being: A Meta-Analysis.
AB  - BACKGROUND: Self-compassion describes a positive and caring attitude of a person
      toward her- or himself in the face of failures and individual shortcomings. As a
      result of this caring attitude, individuals high in self-compassion are assumed
      to experience higher individual well-being. The present meta-analysis examines
      the relationship between self-compassion and different forms of well-being.
      METHOD: The authors combined k = 79 samples, with an overall sample size of N =
      16,416, and analyzed the central tendencies of effect sizes (Pearson correlation
      coefficients) with a random-effect model. RESULTS: We found an overall magnitude
      of the relationship between self-compassion and well-being of r = .47. The
      relationship was stronger for cognitive and psychological well-being compared to
      affective well-being. Sample characteristics and self-esteem were tested as
      potential moderators. In addition, a subsample of studies indicated a causal
      effect of self-compassion on well-being. CONCLUSIONS: The results clearly
      highlight the importance of self-compassion for individuals' well-being. Future
      research should further investigate the relationship between self-compassion and
      the different forms of well-being, and focus on the examination of possible
      additional moderators.

PMID- 26311197
TI  - ESCRTs are everywhere.
AB  - The ESCRT proteins are an ancient system that buds membranes and severs membrane
      necks from their inner face. Three "classical" functions of the ESCRTs have
      dominated research into these proteins since their discovery in 2001: the
      biogenesis of multivesicular bodies in endolysosomal sorting; the budding of HIV
      1 and other viruses from the plasma membrane of infected cells; and the membrane
      abscission step in cytokinesis. The past few years have seen an explosion of
      novel functions: the biogenesis of microvesicles and exosomes; plasma membrane
      wound repair; neuron pruning; extraction of defective nuclear pore complexes;
      nuclear envelope reformation; plus-stranded RNA virus replication compartment
      formation; and micro- and macroautophagy. Most, and perhaps all, of the functions
      involve the conserved membrane-neck-directed activities of the ESCRTs, revealing
      a remarkably widespread role for this machinery through a broad swath of cell
      biology. 

PMID- 26311198
TI  - Family Caregivers and Consumer Health Information Technology.
AB  - Health information technology has been embraced as a strategy to facilitate
      patients' access to their health information and engagement in care. However, not
      all patients are able to access, or are capable of using, a computer or mobile
      device. Although family caregivers assist individuals with some of the most
      challenging and costly health needs, their role in health information technology
      is largely undefined and poorly understood. This perspective discusses challenges
      and opportunities of engaging family caregivers through the use of consumer
      oriented health information technology. We compile existing evidence to make the
      case that involving family caregivers in health information technology as desired
      by patients is technically feasible and consistent with the principles of patient
      centered and family-centered care. We discuss how more explicit and purposeful
      engagement of family caregivers in health information technology could advance
      clinical quality and patient safety by increasing the transparency, accuracy, and
      comprehensiveness of patient health information across settings of care. Finally,
      we describe how clarifying and executing patients' desires to involve family
      members or friends through health information technology would provide family
      caregivers greater legitimacy, convenience, and timeliness in health system
      interactions, and facilitate stronger partnerships between patients, family
      caregivers, and health care professionals. 

PMID- 26311199
TI  - Reducing Implicit Bias Through Curricular Interventions.

PMID- 26311200
TI  - Disparities in the Use of Internet and Telephone Medication Refills among
      Linguistically Diverse Patients.
AB  - BACKGROUND: Health systems are increasingly implementing remote telephone and
      Internet refill systems to enhance patient access to medication refills. Remote
      refill systems may provide an effective approach for improving medication non
      adherence, but more research is needed among patients with limited English
      proficiency with poor access to remote refill systems. OBJECTIVE: To compare the
      use of remote medication refill systems among limited-English-proficiency (LEP)
      and English-proficient (EP) patients with chronic conditions. METHODS: Cross
      sectional survey in six languages/dialects (English, Cantonese, Mandarin, Korean,
      Vietnamese, and Spanish) of 509 adults with diabetes, hypertension, or
      hyperlipidemia. Primary study outcomes were self-reported use of 1) Internet
      refills, 2) telephone refills, and 3) any remote refill system. LEP was measured
      by patient self-identification of a primary language other than English and a
      claims record of use of an interpreter. Other measures were age, gender,
      education, years in the U.S., insurance, health status, chronic conditions, and
      number of prescribed medications. Analyses included multivariable logistic
      regression weighted for survey non-response. RESULTS: Overall, 33.1 % of patients
      refilled their medications by telephone and 31.6 % by Internet. Among LEP
      patients (n = 328), 31.5 % refilled by telephone and 21.2 % by Internet, compared
      with 36.7 % by telephone and 52.7 % by Internet among EP patients (n = 181).
      Internet refill by language groups were as follows: English (52.7 %), Cantonese
      (34.9 %), Mandarin (17.4 %), Korean (16.7 %), Vietnamese (24.4 %), and Spanish
      (12.6 %). Compared to EP patients, LEP patients had lower use of any remote
      refill system (adjusted odds ratio [AOR] 0.18; p < 0.001), CONCLUSIONS: LEP
      patients are significantly less likely than EP patients to use any remote
      medication refill system. Increased reliance on current systems for remote
      medication refills may increase disparities in health outcomes affecting LEP
      patients with poor access to telephone and Internet medication refills.

PMID- 26311201
TI  - Assessing specific deterrence effects of increased speeding penalties using four
      measures of recidivism.
AB  - Traffic law enforcement sanctions can impact on road user behaviour through
      general and specific deterrence mechanisms. The manner in which specific
      deterrence can influence recidivist behaviour can be conceptualised in different
      ways. While any reduction in speeding will have road safety benefits, the ways in
      which a 'reduction' is determined deserves greater methodological attention and
      has implications for countermeasure evaluation more generally. The primary aim of
      this research was to assess the specific deterrent impact of penalty increases
      for speeding offences in Queensland, Australia, in 2003 on two cohorts of drivers
      detected for speeding prior to and after the penalty changes were investigated.
      Since the literature is relatively silent on how to assess recidivism in the
      speeding context, the secondary research aim was to contribute to the literature
      regarding ways to conceptualise and measure specific deterrence in the speeding
      context. We propose a novel way of operationalising four measures which reflect
      different ways in which a specific deterrence effect could be conceptualised: (1)
      the proportion of offenders who re-offended in the follow up period; (2) the
      overall frequency of re-offending in the follow up period; (3) the length of
      delay to re-offence among those who re-offended; and (4) the average number of re
      offences during the follow up period among those who re-offended. Consistent with
      expectations, results suggested an absolute deterrent effect of penalty changes,
      as evidenced by significant reductions in the proportion of drivers who re
      offended and the overall frequency of re-offending, although effect sizes were
      small. Contrary to expectations, however, there was no evidence of a marginal
      specific deterrent effect among those who re-offended, with a significant
      reduction in the length of time to re-offence and no significant change in the
      average number of offences committed. Additional exploratory analyses
      investigating potential influences of the severity of the index offence, offence
      history, and method of detection revealed mixed results. Access to additional
      data from various sources suggested that the main findings were not influenced by
      changes in speed enforcement activity, public awareness of penalty changes, or
      driving exposure during the study period. Study limitations and recommendations
      for future research are discussed with a view to promoting more extensive
      evaluations of penalty changes and better understanding of how such changes may
      impact on motorists' perceptions of enforcement and sanctions, as well as on
      recidivist behaviour. 

PMID- 26311202
TI  - A random parameters probit model of urban and rural intersection crashes.
AB  - Intersections are hazardous locations and many studies have been conducted to
      identify the factors contributing to the frequency and severity of intersection
      crashes. However, little attention has been devoted to investigating the
      differences between crashes at urban and rural intersections, which have
      different road, traffic and environmental characteristics. By applying a random
      parameters probit model to the data from the Canadian Province of Alberta between
      2008 and 2012, we find that urban intersection crashes are more likely to be
      associated with hit and run behaviours, roads with higher traffic volume, wet
      surfaces, four lanes and skewed intersections, and crashes on weekdays and off
      peak hours, whereas rural crashes are likely to be associated with increases in
      fatalities and injuries, roads with higher speed limits, special road features,
      exit and entrance terminals, gravel, curvature and two lanes, crashes during
      weekends, peak hours and night-time, run-off-road crashes, and police visit to
      crash scene. Hence, road safety professionals in urban and rural areas should
      consider these differences when designing and implementing counter-measures to
      improve intersection safety, especially their safety audits and reviews,
      enforcement activities and education campaigns, to target the more vulnerable
      times and locations in the different areas. 

PMID- 26311204
TI  - Preparative separation of bioactive constitutes from Zanthoxylum planispinum
      using linear gradient counter-current chromatography.
AB  - Counter-current chromatography is a chromatographic technique with a support-free
      liquid stationary phase. In the present study, a successful application of linear
      gradient counter-current chromatographic method for preparative isolation of
      bioactive components from the crude ethanol extract of Zanthoxylum planispinum
      was presented. The application of n-hexane/ethyl acetate/methanol/water
      quaternary solvents, in terms of "HEMWat" or "Arizona" solvent families, in
      gradient elution mode was evaluated. Results indicated that slightly proportional
      changes of biphasic liquid systems provided the possibility of gradient elution
      in counter-current chromatography, maintaining stationary phase retention in the
      column. With the selected quaternary solvent systems composed of n-hexane/ethyl
      acetate/methanol/water (2:1:2:1 and 3:2:3:2, v/v), and optimized gradient
      programs, in total seven fractions were separated in 4.5 h. Most of the purified
      compounds could be obtained at the milligram level with over 80% purity. The
      present study indicated that the linear gradient counter-current chromatographic
      approach possessed unique advantages in terms of separation efficiency,
      exhibiting great potential for the comprehensive separation of complex natural
      extracts. 

PMID- 26311203
TI  - Efficient expression of full-length antibodies in the cytoplasm of engineered
      bacteria.
AB  - Current methods for producing immunoglobulin G (IgG) antibodies in engineered
      cells often require refolding steps or secretion across one or more biological
      membranes. Here, we describe a robust expression platform for biosynthesis of
      full-length IgG antibodies in the Escherichia coli cytoplasm. Synthetic heavy and
      light chains, both lacking canonical export signals, are expressed in specially
      engineered E. coli strains that permit formation of stable disulfide bonds within
      the cytoplasm. IgGs with clinically relevant antigen- and effector-binding
      activities are readily produced in the E. coli cytoplasm by grafting antigen
      specific variable heavy and light domains into a cytoplasmically stable framework
      and remodelling the fragment crystallizable domain with amino-acid substitutions
      that promote binding to Fcgamma receptors. The resulting cytoplasmic IgGs-named
      'cyclonals'-effectively bypass the potentially rate-limiting steps of membrane
      translocation and glycosylation.

PMID- 26311205
TI  - Photoshopping the selfie: Self photo editing and photo investment are associated
      with body dissatisfaction in adolescent girls.
AB  - OBJECTIVE: Social media engagement by adolescent girls is high. Despite its
      appeal, there are potential negative consequences for body dissatisfaction and
      disordered eating from social media use. This study aimed to examine, in a cross
      sectional design, the relationship between social media use in general, and
      social media activities related to taking "selfies" and sharing specifically,
      with overvaluation of shape and weight, body dissatisfaction, and dietary
      restraint. METHOD: Participants were 101 grade seven girls (M(age)  = 13.1, SD =
      0.3), who completed self-report questionnaires of social media use and body
      related and eating concerns measures. RESULTS: Results showed that girls who
      regularly shared self-images on social media, relative to those who did not,
      reported significantly higher overvaluation of shape and weight, body
      dissatisfaction, dietary restraint, and internalization of the thin ideal. In
      addition, among girls who shared photos of themselves on social media, higher
      engagement in manipulation of and investment in these photos, but not higher
      media exposure, were associated with greater body-related and eating concerns,
      including after accounting for media use and internalization of the thin ideal.
      DISCUSSION: Although cross-sectional, these findings suggest the importance of
      social media activities for body-related and eating concerns as well as potential
      avenues for targeted social-media-based intervention.

PMID- 26311206
TI  - Effects of ankle balance taping with kinesiology tape for a patient with chronic
      ankle instability.
AB  - [Purpose] To report the effects of ankle balance taping for a patient with
      chronic ankle instability (CAI). [Subject] A 33-year-old man with a 10 year
      history of chronic ankle stability. [Methods] ABT with kinesiology tape was
      performed for 2 months (average, 16 h/day) around the right ankle. [Results] At
      the end of two months, no ankle instability was noted when ascending and
      descending the stairs, jumping, turning, operating the pedals while driving, and
      lifting heavy objects. [Conclusion] The repeated use of kinesiology tape in ankle
      balance taping may be an effective treatment for recovering the ankle stability
      of patients with chronic ankle instability. 

PMID- 26311208
TI  - Evidence-based recommendations on storing and handling specimens for analyses of
      insect microbiota.
AB  - Research on insect microbiota has greatly expanded over the past decade, along
      with a growing appreciation of the microbial contributions to insect ecology and
      evolution. Many of these studies use DNA sequencing to characterize the diversity
      and composition of insect-associated microbial communities. The choice of
      strategies used for specimen collection, storage, and handling could introduce
      biases in molecular assessments of insect microbiota, but such potential
      influences have not been systematically evaluated. Likewise, although it is
      common practice to surface sterilize insects prior to DNA extraction, it is not
      known if this time-consuming step has any effect on microbial community analyses.
      To resolve these methodological unknowns, we conducted an experiment wherein
      replicate individual insects of four species were stored intact for two months
      using five different methods-freezing, ethanol, dimethyl sulfoxide (DMSO),
      cetrimonium bromide (CTAB), and room-temperature storage without preservative-and
      then subjected to whole-specimen 16S rRNA gene sequencing to assess whether the
      structure of the insect-associated bacterial communities was impacted by these
      different storage strategies. Overall, different insect species harbored markedly
      distinct bacterial communities, a pattern that was highly robust to the method
      used to store samples. Storage method had little to no effect on assessments of
      microbiota composition, and the magnitude of the effect differed among the insect
      species examined. No single method emerged as "best," i.e., one consistently
      having the highest similarity in community structure to control specimens, which
      were not stored prior to homogenization and DNA sequencing. We also found that
      surface sterilization did not change bacterial community structure as compared to
      unsterilized insects, presumably due to the vastly greater microbial biomass
      inside the insect body relative to its surface. We therefore recommend that
      researchers can use any of the methods tested here, and base their choice
      according to practical considerations such as prior use, cost, and availability
      in the field, although we still advise that all samples within a study be handled
      in an identical manner when possible. We also suggest that, in large-scale
      molecular studies of hundreds of insect specimens, surface sterilization may not
      be worth the time and effort involved. This information should help researchers
      design sampling strategies and will facilitate cross-comparisons and meta
      analyses of microbial community data obtained from insect specimens preserved in
      different ways. 

PMID- 26311209
TI  - Traumatic Stress during Population-wide Exposure to Trauma in Israel: Gender as a
      Moderator of the Effects of Marital Status and Social Support.
AB  - The 'tend-and-befriend' approach (Taylor et al., ) posits that in times of
      stress, women in particular may tend to their loved ones and seek out social
      support as a coping mechanism. Two corollaries of this model are that when
      confronted with a situation of extreme stress, marriage may be more of a
      protective factor for men, as central beneficiaries of their wives 'tending' or
      nurturing response, and social support from a wider network may be more of a
      protective factor for women, as part of women's 'befriending' response to stress.
      Using a sample of 508 Israelis (M = 47 years; 48% women) under the real condition
      of a population under missile attacks, we investigated the latter two corollaries
      of the tend-and-befriend model, hypothesizing that marriage would buffer against
      symptoms of traumatic stress for men in particular and that social support would
      buffer against symptoms of traumatic stress for women in particular. Our findings
      revealed gender differences affirming both hypotheses and offering interpretive
      evidence in support of the tend-and-befriend model based on a gender-informed
      field study of responses to traumatic stress in real time. Copyright (c) 2015
      John Wiley & Sons, Ltd.

PMID- 26311207
TI  - Emotionally exhausting factors in general practitioners' work.
AB  - BACKGROUND: Emotional exhaustion is central in burnout syndrome and signals its
      development. General practitioners' (GP) work is emotionally challenging but
      research on these aspects is lacking. OBJECTIVE: To study the prevalence of
      emotional exhaustion among GPs and to evaluate how their characteristics and work
      experiences are associated with emotional exhaustion. DESIGN AND METHODS: A
      questionnaire survey was carried out among GPs in Finland in 2011 in which
      questions were posed regarding their experience of emotional exhaustion and items
      related to their work experiences and professional identity. A statement "I feel
      burnt out from my job" (never, seldom, sometimes, quite often, or often) enquired
      about emotional exhaustion. Those responding quite often or often were
      categorized as emotionally exhausted. RESULTS: Among the GPs, 68% responded
      (165/244). Of the respondents, 18% were emotionally exhausted. Emotional
      exhaustion was associated with older age, longer working history, experiences of
      having too much work, fear and reports of having committed a medical error, low
      tolerance of uncertainty in their work, and feeling alone at work. No differences
      in positive work experiences were found. In logistic regression analysis working
      experience > 5 years (OR 4.1, 95% CI 1.6-10.8; p = 0.0036) and feeling alone at
      work (OR 2.9, 95% CI 1.2-7.1; p = 0.020) predicted emotional exhaustion, having
      committed a medical error in the past three months predicted it marginally
      significantly (OR 2.4, 95% CI 1.0-5.9, p = 0.057), whereas tolerating uncertainty
      well protected against it (OR 0.2, 95% CI 0.09-0.7; p = 0.0098). CONCLUSIONS:
      Emotional exhaustion among GPs was common and associated with longer working
      history, having committed a medical error, and feelings of isolation at work. GPs
      should receive more support throughout their careers.

PMID- 26311210
TI  - Pregnancy outcomes among mothers aged 15 years or less.
AB  - AIM: The aim of this study was to determine pregnancy outcomes among early
      adolescent women (aged <= 15 years) compared with those in late adolescence (16
      19 years) and adults aged 20-30 years. MATERIAL AND METHODS: A retrospective
      cohort study was conducted on singleton pregnancies with maternal age <=15 years
      (early adolescent), 16-19 years (late adolescent), and 20-30 years (adult). The
      primary outcomes for comparison were the rates of preterm birth, low birthweight,
      growth restriction and cesarean section. RESULTS: A total of 33 777 pregnancies,
      298 early adolescent, 4456 late adolescent, and 29 023 adults, were enrolled.
      Most baseline characteristics were comparable but rates of pregnancy complicated
      by medical diseases were significantly higher in the adults, especially diabetes
      mellitus and chronic hypertension. When compared to the adult group, the early
      adolescent group had significantly higher rates of preterm birth (31.9% vs 14.5%,
      P < 0.001), growth restriction (11.7% vs 7.1%, P = 0.002), low birthweight (28.9%
      vs 14.7%, P < 0.001), while maternal morbidity, such as pre-eclampsia and
      placenta previa, was similar. Likewise, most of the main outcomes in early
      adolescents were also significantly higher than those in late adolescents, but
      with lesser degrees. Interestingly, the primary cesarean rate was significantly
      lower in early adolescent women (6.7% vs 12.3%, P = 0.005). CONCLUSION: Early
      adolescent pregnancy was associated with higher risks of adverse pregnancy
      outcomes, in particular preterm birth and growth restriction, though most
      maternal morbidity was comparable with that in the control groups. Cesarean rate
      was significantly lower in early adolescent mothers. This information should be
      provided to women and their families.

PMID- 26311212
TI  - Corrigendum: Preferential enhancement of laser-driven carbon ion acceleration
      from optimized nanostructured surfaces.

PMID- 26311213
TI  - Clarifying the anatomy of hearts with concordant ventriculo-arterial connections
      but abnormally related arterial trunks.
AB  - Hearts in which the arterial trunks arise from the morphologically appropriate
      ventricles, but in a parallel manner, rather than the usual spiralling
      arrangement, have long fascinated anatomists. These rare entities, for quite some
      time, were considered embryological impossibilities, but ongoing experience has
      shown that they can be found in various segmental combinations. Problems still
      exist about how best to describe them, as the different variants are often
      described with esoteric terms, such as anatomically corrected malposition or
      isolated ventricular inversion. In this review, based on our combined clinical
      and morphological experience, we demonstrate that the essential feature of all
      hearts described in this manner is a parallel arrangement of the arterial trunks
      as they exit from the ventricular mass. We show that the relationship of the
      arterial roots needs to be described in terms of the underlying ventricular
      topology, rather than according to the arrangement of the atrial chambers. We
      then discuss the importance of determining atrial arrangement on the basis of the
      morphology of the appendages, following the precepts as set out in the so-called
      "morphological method" and distinguished according to the extent of the pectinate
      muscles relative to the atrioventricular junctions as opposed to basing diagnosis
      on the venoatrial connections. We show that, when approached in this manner, the
      various combinations can be readily diagnosed in the clinical setting and
      described in straightforward way. 

PMID- 26311211
TI  - Variation in the Serotonin Transporter Gene and Alcoholism: Risk and Response to
      Pharmacotherapy.
AB  - SLC6A4, the gene encoding the serotonin transporter protein (5-HTT), has been
      extensively examined as a risk factor for alcohol dependence (AD). More recently,
      variability in the transporter gene was identified to be a potential moderator of
      treatment response to serotonergic medications such as ondansetron and
      sertraline. There is an insertion-deletion polymorphism in the promoter region (5
      HTTLPR) of the SLC6A4, with the most common alleles being a 14-repeat short (S)
      allele and a 16-repeat long (L) allele. The S allele has often been associated
      with AD. By contrast, the L allele has been associated with pharmacological
      responsiveness in some individuals with AD. Differences in clinical phenotype may
      determine the utility of the 5-HTTLPR polymorphism as a moderator of
      pharmacological interventions for AD. We review the AD typology and disease onset
      in the context of pharmacogenetic and genomic studies that examine the utility of
      5-HTTLPR in improving treatment outcomes. 

PMID- 26311214
TI  - Proteinuria is associated with sleep apnea in chronic kidney disease.
AB  - BACKGROUND: The prevalence and severity of sleep apnea (SA) in the chronic kidney
      disease (CKD) population is not well characterized. Recent studies have yielded
      highly variable prevalence rates due to cohort heterogeneity and interstudy
      inconsistencies in defining SA. This study sought to determine the association of
      SA with CKD by recruiting a uniform cohort to undertake overnight polysomnography
      (PSG). METHODS: A total of 141 male Chinese CKD patients, ages 40-60 years,
      underwent overnight PSG to delineate the prevalence and severity of SA and
      nocturnal hypoxemia (NH). Body mass index (BMI), neck girth, estimated glomerular
      filtration rate, urinary protein excretion and Epworth sleepiness scale (ESS)
      score were collected at baseline to determine associative factors. RESULTS: The
      prevalence rates of SA and NH were 35.5 and 10.6%, respectively, in this study
      population [mean (+/-SD) age 51.44 +/- 6.05 years; BMI 26.05 +/- 4.22 kg/m(2)].
      The adjusted odds ratios (ORs) for SA by BMI and proteinuria were 1.18 [95%
      confidence interval (CI) 1.02, 1.37; P <= 0.05] and 1.57 (95% CI 1.12, 2.46; P <=
      0.05), respectively. The adjusted ORs for the median cohort oxygen desaturation
      index (ODI) by BMI and proteinuria were 1.23 (95% CI 1.05, 1.45; P <= 0.05) and
      1.75 (95% CI 1.12, 2.76; P <= 0.05). However, no significant correlation between
      the prevalence and severity of SA and NH with progressive renal deterioration was
      observed. Furthermore, no significant mean difference in the apnea-hypopnea index
      and ODI was observed for an ESS above and below 10. CONCLUSIONS: SA is prevalent
      in CKD patients and strongly correlated with BMI and proteinuria, but not with
      renal function. The ESS is an investigative tool that lacks discriminatory power
      in patients with renal insufficiency. Therefore clinical vigilance for SA is
      paramount when attending to CKD patients with significant proteinuria.

PMID- 26311215
TI  - Trends in dialysis modality choice and related patient survival in the ERA-EDTA
      Registry over a 20-year period.
AB  - BACKGROUND: Although previous studies suggest similar patient survival for
      peritoneal dialysis (PD) and haemodialysis (HD), PD use has decreased worldwide.
      We aimed to study trends in the choice of first dialysis modality and relate
      these to variation in patient and technique survival and kidney transplant rates
      in Europe over the last 20 years. METHODS: We used data from 196 076 patients
      within the European Renal Association-European Dialysis and Transplant
      Association (ERA-EDTA) Registry who started renal replacement therapy (RRT)
      between 1993 and 2012. Trends in the incidence rate and prevalence on Day 91
      after commencing RRT were quantified with Joinpoint regression. Crude and
      adjusted hazard ratios (HRs) for 5-year dialysis patient and technique survival
      were calculated using Cox regression. Analyses were repeated using propensity
      score matching to control for confounding by indication. RESULTS: PD prevalence
      dropped since 2007 and HD prevalence stabilized since 2009. Incidence rates of PD
      and HD decreased from 2000 and 2009, respectively, while the incidence of kidney
      transplantation increased from 1993 onwards. Similar 5-year patient survival for
      PD versus HD patients was found in 1993-97 [adjusted HR: 1.02, 95% confidence
      interval (95% CI): 0.98-1.06], while survival was higher for PD patients in 2003
      07 (HR: 0.91, 95% CI: 0.88-0.95). Both PD (HR: 0.95, 95% CI: 0.91-1.00) and HD
      technique survival (HR: 0.93, 95% CI: 0.87-0.99) improved in 2003-07 compared
      with 1993-97. CONCLUSIONS: Although initiating RRT on PD was associated with
      favourable patient survival when compared with starting on HD treatment, PD was
      often not selected as initial dialysis modality. Over time, we observed a
      significant decline in PD use and a stabilization in HD use. These observations
      were explained by the lower incidence rate of PD and HD and the increase in pre
      emptive transplantation.

PMID- 26311217
TI  - Effects of non-pharmacological interventions on urinary citrate levels: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Hypocitraturia is a known risk factor for nephrolithiasis, present in
      20-60% of stone-forming patients. The administration of citrate or other alkali
      preparations has been demonstrated to benefit hypocitraturic stone formers.
      Dietary modifications that include citrate-containing fluids can be an
      alternative option to pharmacological agents. We aimed to systematically review,
      summarize and quantify available evidence on the effects of non-pharmacological
      interventions on urinary citrate and nephrolithiasis. METHODS: Manual and
      electronic database searches (MEDLINE/PubMed, Embase, Cochrane Library, Scopus,
      Scielo, LILACS) were performed for studies published up to July 2014. Two
      reviewers independently identified studies for inclusion and extracted data on
      study characteristics, outcomes and quality assessments. We included controlled
      studies with non-pharmacological interventions that assessed urinary citrate
      levels or nephrolithiasis pre- and post-intervention. Meta-analysis was performed
      by random effects and subgrouped by the type of intervention, and heterogeneity
      was analysed by I(2). RESULTS: Of the 427 studies identified, 13 studies were
      included (18 samples), involving 358 participants with a mean age of 43 +/- 11.0
      years across the studies. Interventions were grouped as commercial fruit juices,
      soft drinks, calcium-/magnesium-rich mineral water, high-fiber diet, low-animal
      protein diet and plant extract. Almost half of the studies (6/13; 8/18 samples)
      reported effects in non-stone formers. Two studies included stone formers and non
      stone formers. Commercial fruit juice interventions showed high I(2) (88.1%, P =
      0.000) and an increase in citraturia levels ( 95% confidence interval) of 167.2
      (65.4; 269) mg/day. Other types of intervention did not show important
      heterogeneity; however, pooled estimates were not significant. CONCLUSION: Our
      review indicates that further larger scale trials are required to analyze whether
      non-pharmacological interventions can increase urinary citrate levels and act in
      kidney stone prevention.

PMID- 26311216
TI  - Comparative outcomes of predominant facility-level use of ferumoxytol versus
      other intravenous iron formulations in incident hemodialysis patients.
AB  - BACKGROUND: Ferumoxytol was first approved for clinical use in 2009 solely based
      on data from trial comparisons with oral iron on biochemical anemia efficacy end
      points. To compare the rates of important patient outcomes (infection,
      cardiovascular events and death) between facilities predominantly using
      ferumoxytol versus iron sucrose (IS) or ferric gluconate (FG) in patients with
      end-stage renal disease (ESRD)-initiating hemodialysis (HD). METHODS: Using the
      United States Renal Data System, we identified all HD facilities that switched
      (almost) all patients from IS/FG to ferumoxytol (July 2009-December 2011). Each
      switching facility was matched with three facilities that continued IS/FG use.
      All incident ESRD patients subsequently initiating HD in these centers were
      studied and assigned their facility exposure. They were followed for all-cause
      mortality, cardiovascular hospitalization/death or infectious
      hospitalization/death. Follow-up ended at kidney transplantation, switch to
      peritoneal dialysis, transfer to another facility, facility switch to another
      iron formulation and end of database (31 December 2011). Cox proportional hazards
      regression was then used to estimate adjusted hazard ratios [HR (95% confidence
      intervals)]. RESULTS: In July 2009-December 2011, 278 HD centers switched to
      ferumoxytol; 265 units (95.3%) were matched with 3 units each that continued to
      use IS/FG. Subsequently, 14 206 patients initiated HD, 3752 (26.4%) in
      ferumoxytol and 10 454 (73.6%) in IS/FG centers; their characteristics were very
      similar. During 6433 person-years, 1929 all-cause, 726 cardiovascular and 191
      infectious deaths occurred. Patients in ferumoxytol (versus IS/FG) facilities
      experienced similar all-cause [0.95 (0.85-1.07)], cardiovascular [0.99 (0.83
      1.19)] and infectious mortality [0.88 (0.61-1.25)]. Among 5513 Medicare (Parts A
      + B) beneficiaries, cardiovascular events [myocardial infarction, stroke and
      cardiovascular death; 1.05 (0.79-1.39)] and infectious events
      [hospitalization/death; 0.96 (0.85-1.08)] did not differ between the iron
      exposure groups. CONCLUSIONS: In incident HD patients, ferumoxytol showed similar
      short- to mid-term safety profiles with regard to cardiovascular, infectious and
      mortality outcomes compared with the more commonly used intravenous iron
      formulations IS and FG.

PMID- 26311218
TI  - Turnover of type III collagen reflects disease severity and is associated with
      progression and microinflammation in patients with IgA nephropathy.
AB  - BACKGROUND: Renal fibrosis is the hallmark of progression to end-stage kidney
      disease. Non-invasive biomarkers of renal fibrosis could serve as specific end
      points in clinical trials and improve monitoring and stratification of patients
      with chronic kidney disease (CKD). To address this, we measured markers of
      collagen type III turnover in urine and serum of IgA nephropathy (IgAN) patients.
      METHODS: We measured the collagen type III pro-peptide (Pro-C3), representing
      production, and a neo-epitope fragment (C3M), representing a specific degradation
      fragment of collagen type III, in urine and serum samples from two cohorts of
      IgAN patients using newly developed enzyme-linked immunosorbent assays. RESULTS:
      With increasing CKD stage, urinary C3M gradually decreased (mean C3M/creatinine:
      17.3 ng/mg in CKD stage 1, 3.5 ng/mg in CKD stage 5) whereas urinary Pro-C3
      gradually increased (mean Pro-C3/creatinine: 4.1 ng/mg in CKD stage 1, 20.8 ng/mg
      in CKD stage 5). The urinary Pro-C3/C3M ratio, a measure of collagen type III
      turnover, significantly increased in advanced CKD stages. Serum C3M was not
      related to CKD stage but was associated with microinflammation. Urinary C3M was
      significantly lower in patients whose CKD stage subsequently progressed compared
      with those who did not progress. CONCLUSIONS: Our results suggest that the
      combination of urinary markers of collagen type III turnover, in particular the
      urinary Pro-C3/C3M ratio, is a potential novel, non-invasive diagnostic and
      prognostic tool to specifically monitor extracellular matrix (ECM) remodelling in
      kidney fibrosis.

PMID- 26311220
TI  - Pyrosequencing analysis of bacterial communities in biofilms from different pipe
      materials in a city drinking water distribution system of East China.
AB  - Biofilms in drinking water distribution systems (DWDSs) could cause several types
      of problems, such as the deterioration of water quality, corrosion of pipe walls,
      and potential proliferation of opportunistic pathogens. In this study, ten
      biofilm samples from different pipe materials, including ductile cast iron pipe
      (DCIP), gray cast iron pipe (GCIP), galvanized steel pipe (GSP), stainless steel
      clad pipe (SSCP), and polyvinyl chloride (PVC), were collected from an actual
      DWDS to investigate the effect of pipe material on bacterial community. Real-time
      quantitative polymerase chain reaction (qPCR) and culture-based method were used
      to quantify bacteria. 454 pyrosequencing was used for bacterial community
      analysis. The results showed that the numbers of total bacteria and culturable
      heterotrophic bacteria from iron pipes were higher than that in PVC, while the
      numbers of Shigella and vibrios were low in biofilms from iron pipes. Bacterial
      community analysis showed that Hyphomicrobium or Desulfovibrio were the
      predominant microorganism in iron pipes, whereas Sphingomonas or Pseudomonas were
      dominant in other types of pipe. This study revealed differences in bacterial
      communities in biofilms among different pipe materials, and the results were
      useful for pipeline material selection in DWDSs. 

PMID- 26311221
TI  - CYP287A1 is a carotenoid 2-beta-hydroxylase required for deinoxanthin
      biosynthesis in Deinococcus radiodurans R1.
AB  - The carotenoid deinoxanthin is a crucial resistance factor against various
      stresses in the radiation-resistant bacterium Deinococcus radiodurans. Disruption
      of the gene dr2473 encoding the cytochrome P450 CYP287A1 led to the accumulation
      of 2-deoxydeinoxanthin in D. radiodurans, demonstrating that CYP287A1 is a novel
      beta-carotene 2-hydroxylase. The dr2473 knockout mutant was shown to be more
      sensitive to UV radiation and oxidative stress than the wild-type strain D.
      radiodurans R1, indicating that the C2 alcohol of deinoxanthin is important for
      antioxidant activity. 

PMID- 26311219
TI  - Hox miRNA regulation within the Drosophila Bithorax complex: Patterning behavior.
AB  - The study of Drosophila Hox genes, located in the Antennapedia complex (ANT-C)
      and Bithorax complex (BX-C), has provided fundamental insights into mechanisms of
      how the segments of the animal body plan are specified. Notably, even though the
      analysis of the BX-C formally began over a century ago, surprises continue to
      emerge regarding its regulation and function. Even simply the gene content of the
      BX-C has been regularly revised in past years, especially with regard to non
      coding RNAs (ncRNAs), including microRNAs. In this perspective, we review the
      history of studies of non-coding transcription in the BX-C, and highlight recent
      studies of its miRNAs that provide new insights into their tissue-specific roles
      in Hox gene regulation. In particular, we have demonstrated unexpected importance
      of endogenous BX-C miRNAs to restrict the spatial accumulation of Hox proteins
      and their TALE cofactors in the ventral nerve cord, and link this to aberrant
      neural differentiation and reproductive behavior. These findings open new
      directions on studying Hox miRNA function, and we speculate that further
      understanding of their roles in insect models may provide new leads for studying
      the enigmatic biological functions of analogous miRNAs located in vertebrate Hox
      clusters. 

PMID- 26311222
TI  - Erratum to: Selective capture of transcribed sequences in the functional gene
      analysis of microbial pathogens.

PMID- 26311223
TI  - Ethnicity-Dependent and -Independent Heterogeneity in Healthy Normal Breast
      Hierarchy Impacts Tumor Characterization.
AB  - Recent reports of widespread genetic variation affecting regulation of gene
      expression raise the possibility of significant inter-individual differences in
      stem-progenitor-mature cell hierarchy in adult organs. This has not been explored
      because of paucity of methods to quantitatively assess subpopulation of normal
      epithelial cells on individual basis. We report the remarkable inter-individual
      differences in differentiation capabilities as documented by phenotypic
      heterogeneity in stem-progenitor-mature cell hierarchy of the normal breast.
      Ethnicity and genetic predisposition are partly responsible for this
      heterogeneity, evidenced by the finding that CD44+/CD24- and PROCR+/EpCAM- multi
      potent stem cells were elevated significantly in African American women compared
      with Caucasians. ALDEFLUOR+ luminal stem/progenitor cells were lower in BRCA1
      mutation carriers compared with cells from healthy donors (p = 0.0014). Moreover,
      tumor and adjoining-normal breast cells of the same patients showed distinct
      CD49f+/EpCAM+ progenitor, CD271+/EpCAM- basal, and ALDEFLUOR+ cell profiles.
      These inter-individual differences in the rate of differentiation in the normal
      breast may contribute to a substantial proportion of transcriptome, epigenome,
      and signaling pathway alterations and consequently has the potential to
      spuriously magnify the extent of documented tumor-specific gene expression.
      Therefore, comparative analysis of phenotypically defined subpopulations of
      normal and tumor cells on an individual basis may be required to identify cancer
      specific aberrations. 

PMID- 26311224
TI  - Expression profile of COL2A1 and the pseudogene SLC6A10P predicts tumor
      recurrence in high-grade serous ovarian cancer.
AB  - Tumor recurrence, following initial response to adjuvant chemotherapy, is a major
      problem in women with high-grade serous ovarian cancer (HGSOC). Microarray
      analysis of primary tumors has identified genes that may be useful in risk
      stratification/overall survival, but are of limited value in predicting the >70%
      rate for tumor recurrence. In this study, we performed RNA-Seq analysis of
      primary and recurrent HGSOC to first identify unique differentially expressed
      genes. From this dataset, we selected 21 archetypical coding genes and one
      noncoding RNA, based on statistically significant differences in their expression
      profile between tumors, for validation by qPCR in a larger cohort of 110 ovarian
      tumors (71 primary and 39 recurrent) and for testing association of specific
      genes with time-to-recurrence (TTR). Kaplan-Meier tests revealed that high
      expression of collagen type II, alpha 1 (COL2A1) was associated with delayed TTR
      (HR = 0.47, 95% CI: 0.27-0.82, p = 0.008), whereas low expression of the
      pseudogene, solute carrier family 6 member 10 (SLC6A10P), was associated with
      longer TTR (HR = 0.53, 95% CI: 0.30-0.93, p = 0.027). Notably, TTR was
      significantly delayed for tumors that simultaneously highly expressed COL2A1 and
      lowly expressed SLC6A10P (HR = 0.21, 95% CI: 0.082-0.54, p = 0.0011), an
      estimated median of 95 months as compared to an estimated median of 16 months for
      subjects expressing other levels of COL2A1 and SLC6A10P. Thus, evaluating
      expression levels of COL2A1 and SLC6A10P at primary surgery could be beneficial
      for clinically managing recurrence of HGSOC.

PMID- 26311226
TI  - Robotic adrenalectomy: the jury is still out.
AB  - A minimally-invasive approach is the gold standard for surgical management of the
      majority of adrenal masses. While laparoscopy has traditionally been used,
      robotic adrenalectomy is becoming increasingly utilized. This article discusses a
      recent systematic review and meta-analysis from European Urology that analyzed
      evidence comparing laparoscopic and robotic adrenalectomy. Robotic adrenalectomy
      is associated with lower blood loss, length of stay and fewer complications
      compared to laparoscopic adrenalectomy; however information on efficacy and cost
      are not addressed. Ultimately, well-done randomized controlled trials (RCTs) are
      necessary to determine the benefits and cost of robotics in adrenal surgery. 

PMID- 26311225
TI  - Effects of CYP2C19 Polymorphism on Endothelial Function, Arterial Stiffness and
      Inflammation in Coronary Artery Disease Patients Under Clopidogrel Treatment.
AB  - BACKGROUND: Clopidogrel's ability to inhibit platelet function determined its
      clinical usefulness. The role of CYP2C19*2 genotype on antiplatelet treatment is
      recently under question. Arterial wall properties and inflammation are key
      players in atherosclerosis development. Hence, we evaluated the impact of
      CYP2C19*2 genetic polymorphism on endothelial function, arterial stiffness and
      inflammation in coronary artery disease (CAD) patients receiving clopidogrel
      treatment. METHODS AND RESULTS: In this study we enrolled 408 consecutive
      patients with stable CAD under dual antiplatelet therapy (clopidogrel 75mg/day,
      aspirin 100mg/day), 30 days after percutaneous coronary intervention. Measurement
      of flow-mediated dilation (FMD) of the brachial artery was used to evaluate
      endothelial function. Carotid-femoral pulse wave velocity (PWV) and augmentation
      index (AIx) was measured to estimate arterial stiffness. Real time polymerase
      chain reaction was used for the genotyping of CYP2C19*2. Levels of tumor necrosis
      factor alpha (TNF-a) and interleukin 6 (IL-6) were measured with ELISA. We found
      no difference in basic clinical and demographic characteristics nor in FMD, PWV,
      AIx and inflammatory status (p=NS for all) between CYP2C19 homozygotes for the
      wild type; carriers of reduced function allele and homozygotes for the reduced
      function allele. CONCLUSION: CYP2C19*2 loss of action polymorphism causes no
      impact on vascular function and inflammatory status in stable CAD patients
      receiving clopidogrel treatment.

PMID- 26311227
TI  - Molecular biomarkers screened by next-generation RNA sequencing for non-sentinel
      lymph node status prediction in breast cancer patients with metastatic sentinel
      lymph nodes.
AB  - BACKGROUND: Non-sentinel lymph node (NSLN) status prediction with molecular
      biomarkers may make some sentinel lymph node (SLN) positive breast cancer
      patients avoid the axillary lymph node dissection, but the available markers
      remain limited. METHODS: SLN positive patients with and without NSLN invasion
      were selected, and genes differentially expressed or fused in SLN metastasis were
      screened by next-generation RNA sequencing. RESULTS: Six candidates (all ER/PR+,
      HER2-, Ki-67 <20%) with metastatic SLNs selected from 305 patients were equally
      categorized as NSLN negative and positive. We identified 103 specifically
      expressed genes in the NSLN negative group and 47 in the NSLN positive group.
      Among them, FABP1 (negative group) and CYP2A13 (positive group) were the only 2
      protein-encoding genes with expression levels in the 8th to 10th deciles. Using a
      false discovery rate threshold of <0.05, 62 up-regulated genes and 98 down
      regulated genes were discovered in the NSLN positive group. Furthermore, 10 gene
      fusions were identified in this group with the most frequently fused gene being
      IGLL5. CONCLUSIONS: The biomarkers screened in present study may broaden our
      understanding of the mechanisms of breast cancer metastasis to the lymph nodes
      and contribute to the axillary surgery selection for SLN positive patients.

PMID- 26311228
TI  - Are there different predictors of analgesic response between antidepressants and
      anticonvulsants in painful diabetic neuropathy?
AB  - BACKGROUND: To investigate baseline demographics and disease characteristics as
      predictors of the analgesic effect of duloxetine and pregabalin on diabetic
      peripheral neuropathic pain (DPNP). METHODS: Based on data from the COMBO-DN
      study, a multinational clinical trial in DPNP, the potential impact of baseline
      characteristics on pain relief after 8-week monotherapy with 60 mg/day duloxetine
      or 300 mg/day pregabalin was assessed using analyses of covariance. Subgroups of
      interest were characterized regarding their baseline characteristics and efficacy
      outcomes. RESULTS: A total of 804 patients were evaluated at baseline. A
      significant interaction with treatment was observed in the mood symptom subgroups
      with a larger pain reduction in duloxetine-treated patients having no mood
      symptoms [Hospital Anxiety and Depression Scale (HADS) depression or anxiety
      subscale score <11; -2.33 (duloxetine); -1.52 (pregabalin); p = 0.024]. There
      were no significant interactions between treatment for subgroups by age (<65 or
      >=65 years), gender, baseline pain severity [Brief Pain Inventory Modified Short
      Form (BPI-MSF) average pain <6 or >=6], diabetic neuropathy duration (<=2 or >2
      years), baseline haemoglobin A1c (HbA1c) (<8% or >=8%), presence of comorbidities
      and concomitant medication use. CONCLUSIONS: Our analyses suggest that the
      efficacy of duloxetine and pregabalin for initial 8-week treatment in DPNP was
      consistent across examined subgroups based on demographics and disease
      characteristics at baseline except for the presence of mood symptoms. Duloxetine
      treatment appeared to be particularly beneficial in DPNP patients having no mood
      symptoms.

PMID- 26311229
TI  - Greedy replica exchange algorithm for heterogeneous computing grids.
AB  - Replica exchange molecular dynamics (REMD) has become a valuable tool in studying
      complex biomolecular systems. However, its application on distributed computing
      grids is limited by the heterogeneity of this environment. In this study, we
      propose a REMD implementation referred to as greedy REMD (gREMD) suitable for
      computations on heterogeneous grids. To decentralize replica management, gREMD
      utilizes a precomputed schedule of exchange attempts between temperatures. Our
      comparison of gREMD against standard REMD suggests four main conclusions. First,
      gREMD accelerates grid REMD simulations by as much as 40 %. Second, gREMD
      increases CPU utilization rates in grid REMD by up to 60 %. Third, we argue that
      gREMD is expected to maintain approximately constant CPU utilization rates and
      simulation wall-clock times with the increase in the number of replicas. Finally,
      we show that gREMD correctly implements the REMD algorithm and reproduces the
      conformational ensemble of a short peptide sampled in our previous standard REMD
      simulations. We believe that gREMD can find its place in large-scale REMD
      simulations on heterogeneous computing grids.

PMID- 26311230
TI  - Mechanistic insights into small molecule activation induced by ligand
      cooperativity in PCcarbeneP nickel pincer complexes: a quantum chemistry study.
AB  - Mechanisms for the activation of water, ammonia, and other small molecules by the
      PCcarbeneP nickel pincer complex were studied computationally with the aid of
      density functional theory. The calculation results indicate that the strongly
      donating, nucleophilic carbene center can engage in a variety of heterolytic
      splitting of E-H (E=H, C, N, O) bonds, some of which are reversible. The cleavage
      of E-H bonds across the Ni=C bond represents a new mode of bond activation by
      ligand cooperativity in nickel pincer complex. On the basis of the calculations,
      we also demonstrate that reversible H2 activation across the Ir=C bond via the
      PCcarbeneP iridium pincer complex was observed in the experiments, while other E
      H (E=C, N, O) bonds were not activated. Our calculations are in good agreement
      with experimental observations and could provide new insights into ligand
      cooperativity in nickel pincer complexes.

PMID- 26311231
TI  - Telephone interpreter discrepancies: videotapes of Hmong medication
      consultations.
AB  - BACKGROUND: Over 25 million people in the USA have limited English proficiency
      (LEP). Interpreters are often used to facilitate communication with health care
      providers. Little is currently known about interpreter quality. OBJECTIVE: To
      explore the quality of telephone interpretation during medication consultations
      between Hmong clients and their pharmacists. METHODS: This descriptive study
      analyzed transcripts from videos of consultations between six triads of Hmong
      patients, pharmacy students and interpreters. Analysis was divided into two
      segments: (1) pharmacy: communication from student pharmacist the interpreter to
      patient and (2) patient: communication from patient to interpreter to student
      pharmacist. Researchers coded transcripts separately then compared codes. KEY
      FINDINGS: The six encounters yielded 496 communications with 275 discrepancies
      including omissions, additions, and word substitutions. Pharmacy to patient
      communications included, 45% (118/262) of omissions, 27.5% (72/262) of
      substitutions, and 15.6% (41/262) of additions. The patient to provider
      communications included, 8.1% (19/234) of omissions, 6.0% (14/234) of
      substitutions, and 4.2% (10/234) of word additions. Some omissions, additions,
      and substitutions in the pharmacy to patient communications were classified as
      potentially clinically relevant. Significantly, substantial discrepancies between
      the student pharmacists' comments and the interpretation to patients had
      potential for hindering relationship building between patients and their
      providers. CONCLUSIONS: Pharmacists may assume that the presence of an
      interpreter ensures accurate communication from pharmacist to patient and from
      patient to pharmacist. This study confirms that those assumptions may not be
      valid. These findings highlight the need to improve pharmacy education and
      interventions to improve pharmacist communication with LEP patients.

PMID- 26311232
TI  - Effects of different three-dimensional electrodes on epiretinal electrical
      stimulation by modeling analysis.
AB  - BACKGROUND: Epiretinal prostheses have been greatly successful in helping restore
      the vision of patients blinded by retinal degenerative diseases. The design of
      stimulating electrodes plays a crucial role in the performance of epiretinal
      prostheses. The objective of this study was to investigate, through computational
      modeling analysis, the effects on the excitation of retinal ganglion cells (RGCs)
      when different three-dimensional (3-D) electrodes were placed in the epiretinal
      space. METHODS: 3-D finite element models of retinal electrical stimulation were
      created in COMSOL using a platinum microelectrode, a vitreous body, multi-layered
      retinal tissue, and retinal pigment epithelium (RPE). Disk and non-planar
      electrodes with different 3-D structures were used in the epiretinal electrical
      stimulation. In addition, a multi-RGC model including ionic mechanisms was
      constructed in NEURON to study the excitability of RGCs in response to epiretinal
      electrical stimulation by different types of electrodes. Threshold current,
      threshold charge density, and the activated RGC area were the three key factors
      used to evaluate the stimulating electrode's performance. RESULTS: As the
      electrode-retina distance increased, both threshold current and threshold charge
      density showed an approximately linear relationship. Increasing the disk
      electrode's diameter resulted in an increase in threshold current and a decrease
      in threshold charge density. Non-planar electrodes evoked different activation
      responses in RGCs than the disk electrode. Concave electrodes produced superior
      stimulation localization and electrode safety while convex electrodes performed
      relatively poorly. CONCLUSIONS: Investigation of epiretinal electrical
      stimulation using different 3-D electrodes would further the optimization of
      electrode design and help improve the performance of epiretinal prostheses. The
      combination of finite element analysis in COMSOL and NEURON software provides an
      efficient way to evaluate the influences of various 3-D electrodes on epiretinal
      electrical stimulation. Non-planar electrodes had larger threshold currents than
      disk electrodes. Of the five types of electrodes, concave hemispherical
      electrodes may be the ideal option, considering their superior stimulation
      localization and electrode safety.

PMID- 26311233
TI  - Hypoglycemic effects of Grifola frondosa (Maitake) polysaccharides F2 and F3
      through improvement of insulin resistance in diabetic rats.
AB  - Our laboratory has previously demonstrated that Grifola frondosa polysaccharides
      (GFPs) showed hypoglycemic effects. This study aimed to investigate which
      polysaccharide-enriched fractions of GFPs were the main active constituents, and
      to disclose their hypoglycemic mechanism. F2 and F3 were obtained from GFPs and
      their hypoglycemic effects were investigated. Fasting serum glucose (FSG) levels,
      fasting serum insulin (FSI) levels and a homeostasis model assessment of insulin
      resistance (HOMA-IR) were measured, and the hepatic mRNA levels of insulin
      receptor (IR), insulin receptor substrate-1 (IRS-1), protein tyrosine phosphatase
      1B (PTP1B), phosphatidylinositol 3-kinase (PI3K) and Akt/protein kinase B (PKB)
      were determined by a quantitative polymerase chain reaction (qPCR). The activity
      of IR and IRS-1 were determined by an enzyme-linked immunosorbent assay (ELISA),
      and their phospho-protein levels were analyzed with western blotting. F2 and F3
      significantly decreased the levels of FSG, FSI and HOMA-IR compared with a
      diabetic control group (P < 0.05). F2 and F3 increased the activity and mRNA
      levels of IR, and the latter also increased the mRNA levels of IRS-1. As for the
      protein levels of phospho-IR and IRS-1, both F2 and F3 increased the protein
      levels of IR (Try 1361), but decreased IRS-1 (Ser307). In the PI3K/Akt pathway,
      F3 increased the mRNA levels of PI3K and Akt, however, F2 inhibited PTP1B
      expression. F2 and F3 are presumed to cause an improvement in insulin resistance,
      triggered by the reactivation of IR and IRS-1. 

PMID- 26311234
TI  - Are label-free investigations the best approach to drug discovery?

PMID- 26311235
TI  - Metabolic dysfunctions in multiple sclerosis: implications as to causation, early
      detection, and treatment, a case control study.
AB  - BACKGROUND: Biochemical changes associated with multiple sclerosis (MS), and its
      various clinical forms have not been characterized well. Therefore, we
      investigated the biochemistry of MS in relation to its natural history using
      targeted lipidomics platforms. METHODS: Cross-sectional serum samples from 24
      secondary progressive (SPMS), 100 relapsing remitting (RRMS), 19 primary
      progressive MS (PPMS), and 55 age-matched control subjects were analyzed by flow
      injection tandem mass spectrometry for very long chain fatty acid (VLCFA)
      containing phosphatidyl ethanolamines (PtdEtn), plasmalogen ethanolamines
      (PlsEtn) and for novel anti-inflammatory gastrointestinal tract acids (GTAs).
      Changes in analyte levels relative to healthy controls were correlated with the
      disease stage and disease duration. RESULTS: RRMS subjects having <13 years
      disease duration had elevated levels (p < 0.05) of anti-inflammatory metabolites
      (GTAs) and normal levels (p > 0.05) of mitochondrial stress biomarkers (VLCFA
      PtdEtn), compared to controls. SPMS subjects had statistically similar levels of
      anti-inflammatory metabolites (GTAs), elevated mitochondrial stress metabolites
      (VLCFA-PtdEtn) and elevated peroxisomal metabolites (PlsEtn) compared to controls
      (p < 0.05). RRMS subjects with > = 13 years disease duration exhibited metabolic
      profiles intermediate between short-duration RRMS and SPMS, based on statistical
      significance. Therefore, RRMS cohort appear to comprise of two metabolically
      distinct subpopulations. The key clinical discriminator of these two groups was
      disease duration. PPMS patients exhibited metabolic profiles distinct from RRMS
      and SPMS. CONCLUSIONS: These data indicate that inflammation and mitochondrial
      stress are intricately involved in the etiology of MS and that progression in MS
      can potentially be monitored using serum metabolic biomarkers.

PMID- 26311236
TI  - Aortopulmonary collateral artery in prenatal exposure to carbamazepine -
      endovascular therapy and technical considerations: a case report.
AB  - INTRODUCTION: Aortopulmonary collateral arteries are an uncommon variant of
      alternative blood supply in cases of complex congenital heart disease. Although
      surgery may still be the classic approach for this condition, mini-invasive
      endovascular occlusion has been recently attempted as an alternative less
      traumatic procedure. Children born to women with epilepsy are at increased risk
      of congenital malformations. CASE PRESENTATION: A cardiovascular malformation in
      a 6-year-old white boy with prenatal exposure to carbamazepine is described. At
      birth, he underwent atrial-ventricular septal defects repair. At 6 years of age,
      he was diagnosed to have an aberrant aortopulmonary artery from the descending
      aorta. He presented with recurrent respiratory infections and no cardiovascular
      signs, but there was associated right upper lobe hyperperfusion. Collateral
      percutaneous plug embolization was performed because of risk for
      cardiorespiratory infections, pulmonary hypertension and atrioventricular
      dilatation. The post-releasing control showed a complete occlusion of the
      aberrant artery. A chest radiogram and computed tomography showed normalization
      of vascular pattern of his right lung at 9-months follow-up. No complications and
      no respiratory infections in the first follow-up year were observed. A good
      growth gain was obtained. CONCLUSIONS: Plug embolization in an aortopulmonary
      collateral artery is an interesting alternative to surgery and is suitable for
      children with minor congenital heart disease and without severe respiratory
      and/or cardiovascular symptoms. Management and long-term pediatric
      multidisciplinary follow-up is recommended. Prenatal exposure to carbamazepine
      could be considered in the pathogenesis and diagnosis of the malformation.

PMID- 26311237
TI  - Temporal fossa defects: techniques for injecting hyaluronic acid filler and
      complications after hyaluronic acid filler injection.
AB  - Facial changes with aging include thinning of the epidermis, loss of skin
      elasticity, atrophy of muscle, and subcutaneous fat and bony changes, all which
      result in a loss of volume. As temporal bones become more concave, and the
      temporalis atrophies and the temporal fat pad decreases, volume loss leads to an
      undesirable, gaunt appearance. By altering the temporal fossa and upper face with
      hyaluronic acid filler, those whose specialty is injecting filler can achieve a
      balanced and more youthful facial structure. Many techniques have been described
      to inject filler into the fossa including a "fanned" pattern of injections,
      highly diluted filler injection, and the method we describe using a three
      injection approach. Complications of filler in the temporal fossa include
      bruising, tenderness, swelling, Tyndall effect, overcorrection, and chewing
      discomfort. Although rare, more serious complications include infection, foreign
      body granuloma, intravascular necrosis, and blindness due to embolization into
      the ophthalmic artery. Using reversible hyaluronic acid fillers, hyaluronidase
      can be used to relieve any discomfort felt by the patient. Injectors must be
      aware of the complications that may occur and provide treatment readily to avoid
      morbidities associated with filler injection into this sensitive area. 

PMID- 26311238
TI  - Selective Connexin43 Inhibition Prevents Isoproterenol-Induced Arrhythmias and
      Lethality in Muscular Dystrophy Mice.
AB  - Duchenne muscular dystrophy (DMD) is caused by an X-linked mutation that leads to
      the absence of dystrophin, resulting in life-threatening arrhythmogenesis and
      associated heart failure. We targeted the gap junction protein connexin43 (Cx43)
      responsible for maintaining cardiac conduction. In mild mdx and severe mdx:utr
      mouse models of DMD, and human DMD tissues, Cx43 was found to be pathologically
      mislocalized to lateral sides of cardiomyocytes. In addition, overall Cx43
      protein levels were markedly increased in mouse and human DMD heart tissues
      examined. Electrocardiography on isoproterenol challenged mice showed that both
      models developed arrhythmias and died within 24 hours, while wild-type mice were
      free of pathology. Administering peptide mimetics to inhibit lateralized Cx43
      function prior to challenge protected mdx mice from arrhythmogenesis and death,
      while mdx:utr mice displayed markedly improved ECG scores. These findings suggest
      that Cx43 lateralization contributes significantly to DMD arrhythmogenesis and
      that selective inhibition may provide substantial benefit. 

PMID- 26311239
TI  - 1alpha,25-Dihydroxyvitamin D3 prevents the differentiation of human lung
      fibroblasts via microRNA-27b targeting the vitamin D receptor.
AB  - Pulmonary fibroblasts have key roles in the formation and maintenance of lung
      structure and function, and are involved in tissue repair and remodeling.
      Transforming growth factor-beta1 (TGF-beta1) induces differentiation of
      fibroblasts into myofibroblasts, the key effector cells in fibrotic states, which
      are characterized by the expression of alpha-smooth muscle actin (alpha-SMA)
      markers. 1alpha,25-Dihydroxyvitamin D3 [1,25(OH)2D3] has been implicated in
      regulating differentiation, and the vitamin D receptor (VDR) may be a regulator
      of TGF-beta signaling. In addition, there is presently only limited information
      regarding microRNA (miRNA) regulation of lung fibroblast differentiation. To
      determine the role of 1,25(OH)2D3 in regulating the differentiation of
      fibroblasts induced by TGF-beta1 and the functional importance of miR-27b, cell
      culture systems, cell transfection and the 3' untranslated region (3'UTR)
      luciferase assay were employed. 1,25(OH)2D3 inhibited differentiation and
      downregulated miR-27b expression in human lung fibroblasts induced by TGF-beta1.
      In addition, human lung fibroblasts were transfected with miR-27b mimic or miR
      27b inhibitor, and demonstrated that the overexpression of miR-27b decreased the
      VDR protein expression and increased the expression of alpha-SMA, while reducing
      levels of miR-27b had opposing effects. Finally, the luciferase reporter assays
      were performed to confirm that miR-27b directly targeted VDR 3'UTR. Taken
      together, these results suggest that 1,25(OH)2D3 inhibits lung fibroblast
      differentiation induced by TGF-beta1 via miR-27b targeting VDR 3'UTR, which may
      be used as a novel treatment strategy in differentiation pathways. 

PMID- 26311240
TI  - Antibiotic prescribing practices for patients with fever in the transition from
      presumptive treatment of malaria to 'confirm and treat' in Zambia: a cross
      sectional study.
AB  - OBJECTIVES: To evaluate antibiotic use among patients presenting to primary
      healthcare facilities with febrile illness in Zambia. METHODS: We analysed data
      from a 2011 nationwide cross-sectional health facility survey of routine malaria
      case management in Zambia. Patient consultation observation and medical record
      charts were used to calculate the proportion of febrile patients who were
      prescribed antibiotics, stratified by symptoms, health workers' diagnosis and
      malaria test results. Logistic regression was used to identify factors affecting
      antibiotic prescribing behaviour. RESULTS: Of 872 patients presenting with fever,
      651 (74.6%) were tested for malaria. Among those tested, 608 (93.4%) had
      analysable results; 230 (37.8%) had positive results. Antibiotics were prescribed
      to 69/230 (30.0%), 247/378 (65.3%) and 132/221 (59.7%) of those who tested
      positive, negative and those 'not tested', respectively. Furthermore, antibiotics
      were prescribed to 36/59 (61.0%) and 242/322 (75.1%) of those diagnosed with
      diarrhoea and upper respiratory tract infection (URTI), respectively. Among
      patients prescribed any antibiotic, concurrent antimalarial prescribing occurred
      in 66/69 (95.6%), 32/247 (12.9%) and 19/132 (14.4%) for those with positive
      results, negative results and 'not tested', respectively. Respiratory symptoms,
      diagnosis of URTI, malaria or skin disease and level of health care in the health
      delivery system were associated with antibiotic prescribing. CONCLUSIONS: Testing
      positive for malaria or receiving a malaria diagnosis was associated with reduced
      antibiotic prescribing, while testing negative, not being tested or a diagnosis
      of URTI resulted in higher rates of antibiotic prescribing. There is a need for
      improving diagnostic capacity for non-malaria causes of febrile illness at
      healthcare delivery points and limiting antibiotic use to patients with definite
      bacterial infections.

PMID- 26311241
TI  - Gremlin1 and chronic pancreatitis: a new clinical target and biomarker?

PMID- 26311242
TI  - Comprehensive Geriatric Assessment is a useful predictive tool for postoperative
      delirium after gastrointestinal surgery in old-old adults.
AB  - AIM: To determine whether carrying out the Comprehensive Geriatric Assessment
      before operations would be useful for predicting complications, particularly
      postoperative delirium (POD), in old-old patients. METHODS: A total of 517
      patients aged 75 years and older, who underwent radical surgery for
      gastrointestinal cancer at Osaka University Hospital, were recruited for this
      observational study. The Comprehensive Geriatric Assessment components and
      assessment of performance status were carried out before surgery, and a record of
      postoperative complications including POD was made prospectively until discharge
      from hospital. The following morphological and clinical measurements were also
      obtained from the medical records: age, sex, disease type, previous history,
      comorbid lifestyle-related diseases, POD, postoperative complications, operative
      method, duration of operation, hemorrhage volume, blood transfusion volume,
      method of anesthesia, body mass index and blood tests. RESULTS: POD appeared in
      24.0% of the 517 patients who underwent surgery. Barthel Index, Mini-Mental State
      Examination, instrumental activities of daily living and Geriatric Depression
      Scale results were associated with the incidence of POD, and the Barthel Index,
      Mini-Mental State Examination and Instrumental Activities of Daily Living results
      were extracted as independent factors associated with the development of POD
      after adjusting for traditional risk factors for postoperative complications and
      performance status. CONCLUSIONS: The Comprehensive Geriatric Assessment before
      gastrointestinal surgery can be a useful tool for predicting the development of
      POD in old-old patients. Geriatr Gerontol Int 2016; 16: 1036-1042.

PMID- 26311244
TI  - Generation and Efficacy Evaluation of a Recombinant Pseudorabies Virus Variant
      Expressing the E2 Protein of Classical Swine Fever Virus in Pigs.
AB  - Classical swine fever (CSF) is an economically important infectious disease of
      pigs caused by classical swine fever virus (CSFV). Pseudorabies (PR), which is
      caused by pseudorabies virus (PRV), is another important infectious disease of
      pigs and other animals. Coinfections of pigs with PRV and CSFV occur occasionally
      in the field. The modified live vaccine Bartha-K61 strain has played an important
      role in the control of PR in many countries, including China. Since late 2011,
      however, increasing PR outbreaks caused by an emerging PRV variant have been
      reported in Bartha-K61-vaccinated swine populations on many farms in China.
      Previously, we generated a gE/gI-deleted PRV (rPRVTJ-delgE) based on this PRV
      variant, which was shown to be safe and can provide rapid and complete protection
      against lethal challenge with the PRV variant in pigs. Here, we generated a new
      recombinant PRV variant expressing the E2 gene of CSFV (rPRVTJ-delgE/gI-E2) and
      evaluated its immunogenicity and efficacy in pigs. The results showed that rPRVTJ
      delgE/gI-E2 was safe for pigs, induced detectable anti-PRV and anti-CSFV
      neutralizing antibodies, and provided complete protection against the lethal
      challenge with either the PRV TJ strain or the CSFV Shimen strain. The data
      indicate that rPRVTJ-delgE/gI-E2 is a promising candidate bivalent vaccine
      against PRV and CSFV coinfections. 

PMID- 26311243
TI  - Pharmacokinetic Herb-Drug Interactions: Insight into Mechanisms and Consequences.
AB  - Herbal medicines are currently in high demand, and their popularity is steadily
      increasing. Because of their perceived effectiveness, fewer side effects and
      relatively low cost, they are being used for the management of numerous medical
      conditions. However, they are capable of affecting the pharmacokinetics and
      pharmacodynamics of coadministered conventional drugs. These interactions are
      particularly of clinically relevance when metabolizing enzymes and xenobiotic
      transporters, which are responsible for the fate of many drugs, are induced or
      inhibited, sometimes resulting in unexpected outcomes. This article discusses the
      general use of herbal medicines in the management of several ailments, their
      concurrent use with conventional therapy, mechanisms underlying herb-drug
      interactions (HDIs) as well as the drawbacks of herbal remedy use. The authors
      also suggest means of surveillance and safety monitoring of herbal medicines.
      Contrary to popular belief that "herbal medicines are totally safe," we are of
      the view that they are capable of causing significant toxic effects and altered
      pharmaceutical outcomes when coadministered with conventional medicines. Due to
      the paucity of information as well as sometimes conflicting reports on HDIs, much
      more research in this field is needed. The authors further suggest the need to
      standardize and better regulate herbal medicines in order to ensure their safety
      and efficacy when used alone or in combination with conventional drugs. 

PMID- 26311245
TI  - Applied Protein and Molecular Techniques for Characterization of B Cell Neoplasms
      in Horses.
AB  - Mature B cell neoplasms cover a spectrum of diseases involving lymphoid tissues
      (lymphoma) or blood (leukemia), with an overlap between these two presentations.
      Previous studies describing equine lymphoid neoplasias have not included analyses
      of clonality using molecular techniques. The objective of this study was to use
      molecular techniques to advance the classification of B cell lymphoproliferative
      diseases in five adult equine patients with a rare condition of monoclonal
      gammopathy, B cell leukemia, and concurrent lymphadenopathy (lymphoma/leukemia).
      The B cell neoplasms were phenotypically characterized by gene and cell surface
      molecule expression, secreted immunoglobulin (Ig) isotype concentrations, Ig
      heavy-chain variable (IGHV) region domain sequencing, and spectratyping. All five
      patients had hyperglobulinemia due to IgG1 or IgG4/7 monoclonal gammopathy.
      Peripheral blood leukocyte immunophenotyping revealed high proportions of IgG1-
      or IgG4/7-positive cells and relative T cell lymphopenia. Most leukemic cells
      lacked the surface B cell markers CD19 and CD21. IGHG1 or IGHG4/7 gene expression
      was consistent with surface protein expression, and secreted isotype and Ig
      spectratyping revealed one dominant monoclonal peak. The mRNA expression of the B
      cell-associated developmental genes EBF1, PAX5, and CD19 was high compared to
      that of the plasma cell-associated marker CD38. Sequence analysis of the IGHV
      domain of leukemic cells revealed mutated Igs. In conclusion, the protein and
      molecular techniques used in this study identified neoplastic cells compatible
      with a developmental transition between B cell and plasma cell stages, and they
      can be used for the classification of equine B cell lymphoproliferative disease. 

PMID- 26311246
TI  - Immunization with Pneumococcal Surface Protein K of Nonencapsulated Streptococcus
      pneumoniae Provides Protection in a Mouse Model of Colonization.
AB  - Current vaccinations are effective against encapsulated strains of Streptococcus
      pneumoniae, but they do not protect against nonencapsulated Streptococcus
      pneumoniae (NESp), which is increasing in colonization and incidence of
      pneumococcal disease. Vaccination with pneumococcal proteins has been assessed
      for its ability to protect against pneumococcal disease, but several of these
      proteins are not expressed by NESp. Pneumococcal surface protein K (PspK), an
      NESp virulence factor, has not been assessed for immunogenic potential or host
      modulatory effects. Mammalian cytokine expression was determined in an in vivo
      mouse model and in an in vitro cell culture system. Systemic and mucosal mouse
      immunization studies were performed to determine the immunogenic potential of
      PspK. Murine serum and saliva were collected to quantitate specific antibody
      isotype responses and the ability of antibody and various proteins to inhibit
      epithelial cell adhesion. Host cytokine response was not reduced by PspK. NESp
      was able to colonize the mouse nasopharynx as effectively as encapsulated
      pneumococci. Systemic and mucosal immunization provided protection from
      colonization by PspK-positive (PspK(+)) NESp. Anti-PspK antibodies were recovered
      from immunized mice and significantly reduced the ability of NESp to adhere to
      human epithelial cells. A protein-based pneumococcal vaccine is needed to provide
      broad protection against encapsulated and nonencapsulated pneumococci in an era
      of increasing antibiotic resistance and vaccine escape mutants. We demonstrate
      that PspK may serve as an NESp target for next-generation pneumococcal vaccines.
      Immunization with PspK protected against pneumococcal colonization, which is
      requisite for pneumococcal disease. 

PMID- 26311247
TI  - Ricinus communis L. stem bark extracts regulate ovarian cell functions and
      secretory activity and their response to Luteinising hormone.
AB  - Ricinus communis L. has ethnopharmacological contraceptive reputation but its
      stem bark has unexplored mechanisms of action in female reproductive system. In
      the present study, the effect of methanolic and aqueous extracts from the stem
      bark of the plant was examined on basic porcine ovarian granulosa cell functions
      and its response to Luteinising hormone (LH)-the upstream hormonal regulator.
      Systemic treatment of methanolic and aqueous extracts stimulated cell
      proliferation (proliferating cell nuclear antigen, PCNA) and also promoted cell
      apoptosis (caspase-3). Aqueous extract has inverted the stimulatory effect of LH
      on PCNA but not on caspase-3. Methanolic extract stimulated as well as inhibited
      progesterone release and stimulated testosterone secretion. Whereas aqueous
      extract inhibited both steroid releases and suppressed the stimulatory effect of
      LH on progesterone release and promoted the inhibitory effect of LH on
      testosterone release. In conclusion, the present study unveils the mechanism of
      action of R. communis stem bark in in vitro condition. These suggest its possible
      contraceptive efficacy by exerting its regulatory role over LH and on basic
      ovarian cell functions and secretion activity. 

PMID- 26311248
TI  - Ex vivo generation of dendritic cells from cryopreserved, post-induction
      chemotherapy, mobilized leukapheresis from pediatric patients with
      medulloblastoma.
AB  - Generation of patient-derived, autologous dendritic cells (DCs) is a critical
      component of cancer immunotherapy with ex vivo-generated, tumor antigen-loaded
      DCs. An important factor in the ability to generate DCs is the potential impact
      of prior therapies on DC phenotype and function. We investigated the ability to
      generate DCs using cells harvested from pediatric patients with medulloblastoma
      for potential evaluation of DC-RNA based vaccination approach in this patient
      population. Cells harvested from medulloblastoma patient leukapheresis following
      induction chemotherapy and granulocyte colony stimulating factor mobilization
      were cryopreserved prior to use in DC generation. DCs were generated from the
      adherent CD14+ monocytes using standard procedures and analyzed for cell
      recovery, phenotype and function. To summarize, 4 out of 5 patients (80%) had
      sufficient monocyte recovery to permit DC generation, and we were able to
      generate DCs from 3 out of these 4 patient samples (75%). Overall, we
      successfully generated DCs that met phenotypic requisites for DC-based cancer
      therapy from 3 out of 5 (60%) patient samples and met both phenotypic and
      functional requisites from 2 out of 5 (40%) patient samples. This study
      highlights the potential to generate functional DCs for further clinical
      treatments from refractory patients that have been heavily pretreated with
      myelosuppressive chemotherapy. Here we demonstrate the utility of evaluating the
      effect of the currently employed standard-of-care therapies on the ex vivo
      generation of DCs for DC-based clinical studies in cancer patients.

PMID- 26311250
TI  - Brachybacterium hainanense sp. nov., isolated from noni (Morinda citrifolia L.)
      branch.
AB  - A Gram-stain-positive bacterial strain, designated as NR2T, isolated from noni
      (Morinda citrifolia L.) branch was investigated using a polyphasic taxonomic
      approach. The cells were small coccoid to ovoid, non-spore-forming and motile.
      Phylogenetic analysis based on 16S rRNA gene sequences showed that the strain was
      a representative of a member of the genus Brachybacterium, to which the most
      closely related neighbours were Brachybacterium squillarum M-6-3T (97.90 %
      similarity), Brachybacterium faecium DSM 4810T (97.50 %), Brachybacterium sacelli
      LMG 20345T (97.41 %), Brachybacterium phenoliresistens phenol-AT (97.36 %),
      Brachybacterium nesterenkovii DSM 9573T (97.36 %) and Brachybacterium rhamnosum
      LMG 19848T (97.32 %). The polar lipid profile of strain NR2T consisted of
      diphosphatidylglycerol, phosphatidylglycerol, unknown phospholipids and unknown
      glycolipids. The predominant respiratory quinone was MK-8, with MK-9 and MK-7 as
      minor components. The major fatty acids were anteiso-C15 : 0 and iso-C15 : 0.
      Strain NR2T was clearly distinguishable from the type strains of related species
      on the basis of phylogenetic analysis, DNA-DNA hybridization, fatty acid
      composition data analysis and a range of physiological and comparison of
      biochemical characteristics. It is evident from the genotypic and phenotypic data
      that strain NR2T represents a novel species of the genus Brachybacterium, for
      which the name Brachybacterium hainanense sp. nov. is proposed. The type strain
      is NR2T ( = DSM 29535T = CICC 10874T).

PMID- 26311249
TI  - Investigating a signature of temozolomide resistance in GBM cell lines using
      metabolomics.
AB  - Glioblastoma multiforme (GBM) is the most common form of malignant glioma.
      Current therapeutic approach to treat this malignancy involves a combination of
      surgery, radiotherapy and chemotherapy with temozolomide. Numerous mechanisms
      contributing to inherent and acquired resistance to this chemotherapeutic agent
      have been identified and can lead to treatment failure. This study undertook a
      metabolomics-based approach to characterize the metabolic profiles observed in
      temozolomide-sensitive and temozolomide-resistant GBM cell lines as well as in a
      small sub-set of primary GBM tumors. This approach was also utilized to explore
      the metabolic changes modulated upon cell treatment with temozolomide and
      lomeguatrib, an MGMT inhibitor with temozolomide-sensitizing potential.
      Metabolites previously explored for their potential role in chemoresistance
      including glucose, citrate and isocitrate demonstrated elevated levels in
      temozolomide-resistant GBM cells. In addition, a signature of metabolites
      comprising alanine, choline, creatine and phosphorylcholine was identified as up
      regulated in sensitive GBM cell line across different treatments. These results
      present the metabolic profiles associated with temozolomide response in selected
      GBM models and propose interesting leads that could be leveraged for the
      development of therapeutic or diagnostic tools to impact temozolomide response in
      GBMs. 

PMID- 26311251
TI  - CspC regulates the expression of the glyoxylate cycle genes at stationary phase
      in Caulobacter.
AB  - BACKGROUND: The Cold Shock proteins are RNA binding proteins involved in various
      cellular processes, including adaptation to low temperature, nutritional stress,
      cell growth and stationary phase. They may have an impact on gene expression by
      interfering with RNA stability and acting as transcription antiterminators.
      Caulobacter crescentus cspC is an essential gene encoding a stationary phase
      induced protein of the Cold Shock Protein family and this work had as goal
      investigating the basis for the requirement of this gene for survival at this
      phase. In this work we investigate the role of CspC in C. crescentus stationary
      phase and discuss the molecular mechanisms that could be involved. RESULTS: The
      expression of cspC increased significantly at stationary phase in complex media
      and in glucose depletion, indicating a putative role in responding to carbon
      starvation. Global transcriptional profiling experiments comparing cspC and the
      wild type strain both at exponential and stationary phases as well as comparing
      exponential and stationary phase in wild type strain were carried out by DNA
      microarray analysis. The results showed that the absence of cspC affected the
      transcription of 11 genes at exponential phase and 60 genes at stationary phase.
      Among the differentially expressed genes it is worth noting those encoding
      respiratory enzymes and genes for sulfur metabolism, which were upregulated, and
      those encoding enzymes of the glyoxylate cycle, which were severely downregulated
      in the mutant at stationary phase. mRNA decay experiments showed that the aceA
      mRNA, encoding isocitrate lyase, was less stable in the cspC mutant, indicating
      that this effect was at least partially due to posttranscriptional regulation.
      These observations were supported by the observed arrested growth phenotype of
      the cspC strain when grown in acetate as the sole carbon source, and by the
      upregulation of genes for assimilatory sulfate reduction and methionine
      biosynthesis. CONCLUSIONS: The stationary phase-induced RNA binding protein CspC
      has an important role in gene expression at this phase, and is necessary for
      maximal expression of the glyoxylate cycle genes. In the case of aceA, its
      downregulation may be attributed to the shorter half-life of the mRNA in the cspC
      mutant, indicating that one of the possible regulatory mechanisms is via altering
      RNA stabilization.

PMID- 26311252
TI  - The behavioral and cultural stratigraphic contexts of the lithic assemblages from
      Schoningen.
AB  - Within the various archaeological horizons in Schoningen, the presence of
      hominins is repeatedly demonstrated by the recovery of stone artifacts, broken
      bones, and bones with cut marks. The Spear Horizon, 13 II-4, with its ca. 1500
      stone artifacts and ca. 12,000 faunal remains, represents by far the richest
      archaeological layers in Schoningen. Systematic waterscreening over a period of
      15 years has fostered the recovery of numerous small flakes that otherwise would
      have remained undetected. Based on the stone artifacts published by H. Thieme and
      the lithic artifacts recovered from the ongoing excavations of the University of
      Tubingen and the Archaeological Heritage Office of Lower Saxony since 2008, we
      present here the main aspects of these lithic assemblages. The main features of
      the lithic assemblages recovered from the different find horizons and
      concentrations provide a consistent signature, suggesting a robust and repetitive
      technological strategy. The assemblages, which are made of local, high quality
      flint, lack handaxes and are clearly not related to the Acheulean. Intensely
      retouched scrapers, as well as denticulates, notched pieces, and points on thick
      flakes, angular debris, and non-anthropogenic thermal spalls are the most
      numerous retouched forms. The assemblages also contain a smaller number of
      thinner forms. Reduction sequences are short and Levallois technology is absent.
      Although some of the retouched forms are reminiscent of the Middle Paleolithic,
      the relatively non-standardized short reduction sequences technically oriented
      toward the production of thick and broad flakes are consistent with a
      classification in the late Lower Paleolithic.

PMID- 26311253
TI  - Computed modeling of alternating electric fields therapy for recurrent
      glioblastoma.
AB  - Tumor treating fields (TTFields) are alternating electric fields frequency tuned
      to 200 kHz for the treatment of recurrent glioblastoma. We report a patient
      treated with TTFields and determined the distribution of TTFields intracranially
      by computerized simulation using co-registered postgadolinium T1-weighted, T2,
      and MP RAGE images together with pre-specified conductivity and relative
      permittivity values for various cerebral structures. The distribution of the
      electric fields within the brain is inhomogeneous. Higher field intensities were
      aggregated near the ventricles, particularly at the frontal and occipital horns.
      The recurred tumor was found distant from the primary glioblastoma and it was
      located at a site of relatively lower electric field intensity. Future
      improvement in TTFields treatment may need to take into account the inhomogeneity
      of the electric field distribution within the brain.

PMID- 26311255
TI  - The Effects of Organization Design and Patient Perceptions of Care on Switching
      Behavior and Reliance on a Health Care System Across Time.
AB  - Sustaining ongoing relationships with patients is a strategic, clinically
      relevant goal of health care systems. This study develops and tests a conceptual
      model that aims to account for the influence of organization design, perceptions
      of quality of patient care, and other patient-level factors on the extent to
      which patients sustain reliance on a health care system. We use a longitudinal
      survey design and structural equation modeling to predict increases or decreases
      in patient reliance on the Department of Veterans Affairs health care system
      across a 4-year period for Veterans with Parkinson's Disease. Our findings show
      that specialized and integrated clinical practices have a positive association
      with the quality of patient care. Health care systems may be able to foster long
      term relations with patients and improve service quality by allocating resources
      to form integrated, specialized, disease-specific centers of care designed for
      patients with chronic illnesses.

PMID- 26311254
TI  - Feasibility of Cowpea chlorotic mottle virus-like particles as scaffold for
      epitope presentations.
AB  - BACKGROUND & METHODS: Within the last decade Virus-Like Particles (VLPs) have
      increasingly received attention from scientists for their use as a carrier of
      (peptide) molecules or as scaffold to present epitopes for use in subunit
      vaccines. To test the feasibility of Cowpea chlorotic mottle virus (CCMV)
      particles as a scaffold for epitope presentation and identify sites for epitope
      fusion or insertion that would not interfere with virus-like-particle formation,
      chimeric CCMV coat protein (CP) gene constructs were engineered, followed by
      expression in E. coli and assessment of VLP formation. Various constructs were
      made encoding a 6x-His-tag, or selected epitopes from Influenza A virus [IAV]
      (M2e, HA) or Foot and Mouth Disease Virus [FMDV] (VP1 and 2C). The epitopes were
      either inserted 1) in predicted exposed loop structures of the CCMV CP protein,
      2) fused to the amino- (N) or carboxyl-terminal (C) ends, or 3) to a N-terminal
      24 amino acid (aa) deletion mutant (N?24-CP) of the CP protein. RESULTS: High
      levels of insoluble protein expression, relative to proteins from the entire cell
      lysate, were obtained for CCMV CP and all chimeric derivatives. A straightforward
      protocol was used that, without the use of purification columns, successfully
      enabled CCMV CP protein solubilization, reassembly and subsequent collection of
      CCMV CP VLPs. While insertions of His-tag or M2e (7-23 aa) into the predicted
      external loop structures did abolish VLP formation, high yields of VLPs were
      obtained with all fusions of His-tag or various epitopes (13- 27 aa) from IAV and
      FMDV at the N- or C-terminal ends of CCMV CP or N?24-CP. VLPs derived from CCMV
      CP still encapsulated RNA, while those from CCMV CP-chimera containing a
      negatively charged N-terminal domain had lost this ability. The usefulness and
      rapid ease of exploitation of CCMV VLPs for the production of potential subunit
      vaccines was demonstrated with the synthesis of chimeric CCMV VLPs containing
      selected sequences from the GN and GC glycoproteins of the recently emerged
      Schmallenberg orthobunyavirus at both termini of the CP protein. CONCLUSIONS:
      CCMV VLPs can be successfully exploited as scaffold for epitope fusions up to 31
      aa at the N- and C-terminus, and at a N-terminal 24 amino acid (aa) deletion
      mutant (N?24-CP) of the CP protein.

PMID- 26311256
TI  - Characterization of NAD salvage pathways and their role in virulence in
      Streptococcus pneumoniae.
AB  - NAD is a necessary cofactor present in all living cells. Some bacteria cannot de
      novo synthesize NAD and must use the salvage pathway to import niacin or
      nicotinamide riboside via substrate importers NiaX and PnuC, respectively.
      Although homologues of these two importers and their substrates have been
      identified in other organisms, limited data exist in Streptococcus pneumoniae,
      specifically, on its effect on overall virulence. Here, we sought to characterize
      the substrate specificity of NiaX and PnuC in Str. pneumoniae TIGR4 and the
      contribution of these proteins to virulence of the pathogen. Although binding
      affinity of each importer for nicotinamide mononucleotide may overlap, we found
      NiaX to specifically import nicotinamide and nicotinic acid, and PnuC to be
      primarily responsible for nicotinamide riboside import. Furthermore, a pnuC
      mutant is completely attenuated during both intranasal and intratracheal
      infections in mice. Taken together, these findings underscore the importance of
      substrate salvage in pneumococcal pathogenesis and indicate that PnuC could
      potentially be a viable small-molecule therapeutic target to alleviate disease
      progression in the host. 

PMID- 26311257
TI  - Epiretinal proliferation in lamellar macular holes and full-thickness macular
      holes: clinical and surgical findings.
AB  - PURPOSE: To report the clinical findings and surgical outcomes of lamellar
      macular holes (LMH) with or without lamellar hole-associated epiretinal
      proliferation (LHEP), and those of full-thickness macular holes (FTMH) presenting
      with LHEP. METHODS: From 2009 to 2013, consecutive cases of surgically treated
      LMH, and all FTMH cases with LHEP were reviewed, given a follow-up time over 1
      year. RESULTS: In the LMH group (43 cases), those with LHEP (19 cases) had
      significantly thinner bases and larger openings than those without (24 cases).
      The rate of disrupted IS/OS line was higher in the LHEP subgroup preoperatively
      (68.4 % vs 37.5 %), but similar between subgroups postoperatively (36.8 % and
      33.3 %). The preoperative and postoperative visual acuity showed no significant
      difference between two subgroups. In the FTMH group (13 cases), the average hole
      size was 219.2 +/- 92.1 MUm. Permanent or transient spontaneous hole closure was
      noted in 69.2 % of cases. An intact IS-OS line was found in only 23 % of cases at
      the final follow-up. CONCLUSION: In the LMH group, LHEP was associated with a
      more severe defect but didn't affect surgical outcomes. In the FTMH group,
      spontaneous hole closure was frequently noted. Despite small holes, disruption of
      IS-OS line was common after hole closure.

PMID- 26311259
TI  - Reliability of a new modified tear breakup time method: methodological and
      statistical issues.

PMID- 26311258
TI  - Dark adaptation-induced changes in rod, cone and intrinsically photosensitive
      retinal ganglion cell (ipRGC) sensitivity differentially affect the pupil light
      response (PLR).
AB  - PURPOSE: Our purpose was to explore pupil light response (PLR) with respect to
      the change in sensitivity of photoreceptors during various dark adaptation phases
      and to determine the optimal duration of dark adaptation time before the PLR.
      METHODS: The PLR was recorded in 15 healthy subjects and three patients with
      neural or retinal vision loss after 1-sec blue and red light stimuli of 1, 10,
      and 100 cd/m(2). The PLR was repeated nine times at different checkpoints during
      the 40-minute dark adaptation. The transient contraction amplitude, sustained
      contraction amplitude, and relative sustained contraction ratio of the PLR were
      analyzed. RESULTS: The increase in the transient contraction amplitude during the
      entire dark adaptation process was significant (changing up to 45.1 %) in the
      initial phase of dark adaptation under different stimulus conditions. The changes
      in the sustained contraction amplitude and the relative sustained contraction
      ratio were substantial (changing up to 71.0 % and 37.2 % from 1 to 20 minutes of
      dark adaptation, respectively) under high-intensity blue illumination. The
      inflection point of the contraction curves in the dark adaptation was 15 or 20
      minutes. The patients' PLR results changed in a similar manner. CONCLUSIONS: The
      changes in the sensitivity of different photoreceptors occurred at different
      rates, and the contraction amplitude of the PLR was significantly affected by the
      dark adaptation duration. So 20 minutes of dark adaptation before PLR testing was
      suggested to achieve a consistent and stable pupil response. The dark adaptation
      effect should be put into consideration when comparing the results from different
      phases of the PLR test.

PMID- 26311260
TI  - Reliability of a new modified tear breakup time method: introduction of dry tear
      breakup time.

PMID- 26311261
TI  - Long-term efficacy of abatacept in pediatric patients with idiopathic uveitis: a
      case series.
AB  - BACKGROUND: Non-infectious uveitis represents one of the most common causes of
      blindness, even at pediatric age; in particular, idiopathic chronic uveitis can
      pose significant difficulties during treatment, due to a partial response to TNF
      alpha antagonists. To date, very few case series exist describing the treatment
      of idiopathic uveitis not adequately controlled by TNF-alpha antagonists. The aim
      of our study is to describe the role of abatacept in achieving remission in
      patients with idiopathic uveitis previously treated with TNF-alpha antagonists,
      and to assess how long abatacept efficacy is maintained during follow-up. The
      treatment's safety profile and tolerability were also specifically investigated.
      METHODS: Three patients affected with chronic idiopathic uveitis, who have been
      treated with abatacept due to loss of efficacy of TNF-alpha antagonists, were
      reviewed. Details of the demographic and clinical characteristics were recorded,
      and a summary of the medical history was obtained. Patients were regularly
      reviewed in the ophthalmology and rheumatology clinics. Assessment of their
      ocular condition was characterized according to the Standardization of Uveitis
      Nomenclature (SUN) group. RESULTS: In our patients, abatacept was able to induce
      remission and to discontinue systemic corticosteroids after a mean of 30 weeks;
      the drug maintained its efficacy through a long follow-up period (42, 33, and 18
      months respectively), with an excellent safety profile. CONCLUSION: Our small
      case series seems to suggest abatacept to be a promising therapy in children
      affected with chronic idiopathic uveitis not adequately controlled by TNF-alpha
      antagonists.

PMID- 26311263
TI  - Historic change in catchment land use and metal loading to Sydney estuary,
      Australia (1788-2010).
AB  - Sydney estuary has a long history of environmental degradation and is one of the
      most modified water ways in Australia due to a highly urbanised catchment (~77 %)
      and a high population (4.6 million). The objectives of the present study were to
      map historical land use change from European settlement (1788) to 2010 to
      determine catchment evolutionary pathways and to estimate catchment loading
      (total suspended solids, Cu, Pb and Zn) to the estuary over this period. Land use
      distribution in Sydney catchment, determined for seven time horizons over this
      period, indicated that a substantial increase in residential land use through
      subdivision of large estates and an increase in road area resulted in a marked
      increase in metal loading to Sydney estuary between 1892 and 1936. The decline in
      industrial activity from a maximum in 1978 (3.9 %) to 1.8 % in 2010 and the
      introduction of unleaded fuel during this time was accompanied by reduction in
      metal loading to the estuary. Land use time horizon maps enabled the creation of
      novel, ternary diagrams to represent temporal evolution in catchment land use.
      The 15 sub-catchments of Sydney estuary were combined into three major catchment
      categories, i.e., urban, dense urban and commercial. Present-day annual discharge
      of stormwater from the Sydney catchment was calculated to be 466,000 ML and
      annual loadings of total suspended sediment (TSS), Cu, Pb and Zn in tonnes were
      49,239, 27, 37 and 57, respectively. Stormwater has superseded industry as the
      main source of anthropogenic metals to this estuary in recent times.

PMID- 26311262
TI  - Recessive Stargardt disease phenocopying hydroxychloroquine retinopathy.
AB  - PURPOSE: To describe a series of patients with Stargardt disease (STGD1)
      exhibiting a phenotype usually associated with hydroxychloroquine (HCQ)
      retinopathy on spectral domain-optical coherence tomography (SD-OCT). METHODS:
      Observational case series from Columbia University Medical Center involving eight
      patients with genetically-confirmed STGD1. Patients selected for the study
      presented no history of HCQ use. Horizontal macular SD-OCT scans and accompanying
      488-nm autofluorescence (AF) images, color fundus photographs, and full-field
      electroretinograms were analyzed. RESULTS: All study patients exhibited an abrupt
      thinning of the parafoveal region or disruption of the outer retinal layers on SD
      OCT resembling the transient HCQ retinopathy phenotype. Funduscopy and AF imaging
      revealed variations of bull's eye maculopathy (BEM). Five patients exhibited
      local fleck-like deposits around the lesion. Genetic screening confirmed two
      disease-causing ABCA4 mutations in five patients and one mutation in three
      patients. CONCLUSIONS: A transient SD-OCT phenotype ascribed to patients with HCQ
      retinopathy is associated with an early subtype of STGD1. This finding may also
      present with HCQ retinopathy-like BEM lesions on AF imaging and funduscopy. A
      possible phenotypic overlap is unsurprising, given certain shared mechanistic
      disease processes between the two conditions. A thorough work-up, including
      screening of genes that are causal in retinal dystrophies associated with foveal
      sparing, may prevent misdiagnosis of more ambiguous cases.

PMID- 26311264
TI  - Assessment of the restoration measures in a man-made reservoir: do oligochaete
      communities respond to the improvement of water quality?
AB  - Studies were carried out in a man-made reservoir that was undergoing restoration
      using selective hypolimnetic withdrawal (Plawniowice reservoir, Southern Poland).
      The aim of the research was to assess the changes in the composition of
      oligochaete fauna in relation to water quality and to estimate whether indices
      based on oligochaetes may be useful in the assessment of a reservoir's recovery
      from eutrophication. Samples were collected in the first, fifth, and eighth year
      of the restoration during the summer stratification at 22 sites along six
      transects that covered depths from 2 to 15 m. The results of the survey indicated
      an improvement in some physical and chemical water parameters in respect to those
      during the period prior to the restoration measures. The present study showed an
      increase in the oligochaete diversity and a decrease in their abundance
      accompanied by a shift toward a larger share of taxa that are characteristic of
      mesotrophic and oligotrophic conditions. This study detected slow changes in the
      values of the trophic indices based on oligochaetes toward mesotrophic
      conditions. Discriminant analysis, performed using stepwise forward selection,
      demonstrated a good separation of samples from 2004 and 2011 according to trophic
      condition (TC) and biotic quality index (BQI) indices. The present data shows
      that metrics based on Oligochaeta may be useful for detecting changes in the
      trophic status.

PMID- 26311265
TI  - Seasonal variation of nutrient loads in treated wastewater effluents and
      receiving water bodies in Sedibeng and Soshanguve, South Africa.
AB  - The discharge of inadequately treated wastewater effluent presents a major threat
      to the aquatic environment and public health worldwide. As a water-scarce
      country, South Africa is facing an alarming situation since most of its
      wastewater discharges are not meeting the permissible limit. The aim of this
      study was to assess the physicochemical quality of treated wastewater effluents
      and their impact on receiving water bodies. During the study period, pH,
      temperature, free chlorine residue (Cl(-)), dissolved oxygen (DO), nitrate (NO3 (
      1)), orthophosphate (PO4 (-3)) and chemical oxygen demand (COD) were measured in
      order to ascertain whether the selected wastewater systems in Sedibeng and
      Soshanguve complied with the South African and World Health Organization
      standards during wet and dry seasons. These parameters were analysed for samples
      collected from raw wastewater influent, treated wastewater effluent and receiving
      water bodies. The study was carried out between August 2011 and May 2012, and
      samples were collected on a weekly basis during both seasons. The physicochemical
      quality of effluents did not comply with the regulatory limits set by South
      Africa in terms of pH in Meyerton, Rietgat and Sandspruit (pH 7.6 to 8.1); free
      chlorine in Sandspruit (0.27 +/- 0.05 mg/L); nitrate in Leeuwkuil and Rietgat
      (2.1 and 3.8 mg/L, respectively) during the wet season; orthophosphate in
      Meyerton during the wet season and in Sandspruit during the dry season (1.3 mg
      PO4 (-3) as P/L and 1.1 mg PO4 (-3) as P/L, respectively); and chemical oxygen
      demand in Rietgat during the dry season and in Sandspruit during the wet season
      (75.5 and 35 mg/L, respectively). Furthermore, the quality of the receiving water
      bodies did not comply with the South African standards recommended for pH,
      chemical oxygen demand and orthophosphate and DO (5 mg/L) in Rietgat during the
      wet season. The geometric mean of the water quality index values ranged between
      32.4 and 36.9 for the effluent samples and between 38.1 and 65.7 for the
      receiving water bodies. These findings revealed that the receiving water bodies
      were classified as having "poor" quality status, except Leeuwkuil receiving water
      body (Vaal River) and Sandspruit upstream (Sandspruit stream). The dry season
      showed a relatively lower water quality index. This situation might be attributed
      to the higher amount of organic matter and lower microbial activities in the
      receiving water bodies. This study suggests that wastewater effluents and
      receiving water systems should be monitored regularly to ensure best practices
      with regard to nutrient treatment and discharge of wastewater.

PMID- 26311266
TI  - Enrichment of arsenic in the Quaternary sediments from Ankaleshwar industrial
      area, Gujarat, India: an anthropogenic influence.
AB  - Arsenic (As) contamination of sediments and waters is known from Bengal and other
      parts of eastern and central India. However, there is paucity of reports that
      document occurrence of As in Quaternary sediments from western India. In this
      paper, we report the enrichment of As in the Quaternary sediments of Ankaleshwar
      area in the western Indian state of Gujarat. Twenty-five surface and five profile
      samples were analyzed that indicated spatial and vertical distribution of As in
      the sediments. The As content of fine size fractions (<63 MUm) compared with
      upper continental crust (UCC) and standard shale indicates anomalous As
      enrichment that is supported by moderate to high geo-accumulation index (Igeo) as
      well as pollution index (Pi). Enrichment of As is seen in surface sediments from
      the industrial and urban land use regions, followed by oil field and agricultural
      land suggesting strong influence of anthropogenic factors. Although the arsenic
      concentration decreases with depth, the relatively higher values of As coupled
      with Igeo and Pi index values suggest downward migration of metal that is likely
      to contaminate groundwater. This calls for urgent remediation so that the ill
      effects of As contamination can be minimized.

PMID- 26311267
TI  - Determination of the personal, indoor and outdoor exposure levels of inorganic
      gaseous pollutants in different microenvironments in an industrial city.
AB  - We measured SO2, NO2 and O3 concentrations during the summer and winter in
      Kocaeli, Turkey. The sampling was carried out indoors and outdoors at homes,
      schools and offices. Personal samplers were also used to determine personal
      exposures to these pollutants. High NO2 and SO2 concentrations were observed in
      outdoor samples collected close to locations characterized by heavy urban
      traffic. Concentrations of O3, on the other hand, were higher in rural areas
      around the city due to ozone distillation. For both sampling periods, the
      concentrations of outdoor SO2 and O3 were higher than for indoor and personal
      samples; however, the NO2 concentrations were higher in indoor and personal
      samples, indicating that outdoor sources significantly contribute to indoor SO2
      and O3 levels and that indoor NO2 concentrations are primarily modulated by
      sources within buildings. Seasonal variations in pollutant concentrations showed
      statistically significant differences. Indoor and outdoor concentrations of NO2
      and SO2 measured in the winter were higher than the levels measured in the
      summer; O3 concentrations, on the other hand, exhibited the opposite trend.
      Active-to-passive concentration ratios for NO2, SO2 and O3 were 0.99, 1.08 and
      1.16, respectively; the corresponding outdoor ratios were 0.95, 0.99 and 1.00. 

PMID- 26311268
TI  - Distribution and risk assessment of hydrocarbons (aliphatic and PAHs),
      polychlorinated biphenyls (PCBs), and pesticides in surface sediments from an
      agricultural river (Durance) and an industrialized urban lagoon (Berre lagoon),
      France.
AB  - The distributions of organic pollutants (like hydrocarbons, polychlorinated
      biphenyls (PCBs), and pesticides) and the risks on the ecosystem were studied in
      the Durance River and the Berre lagoon (France). High levels of aliphatic
      hydrocarbons were observed in all stations (1399 to 11,202 MUg kg(-1) dw). The n
      alkanes were mainly from terrigenous origin confirmed by the values of different
      ratios calculated (carbon preference index (CPI), natural n-alkanes ratio (NAR),
      terrigenous/aquatic ratio (TAR), and ratio of low molecular weight to high
      molecular weight (LMW/HMW)). Total polycyclic aromatic hydrocarbon (PAH)
      concentrations in the surface sediments of the Durance River and Berre lagoon are
      57-1528 and 512-863 MUg kg(-1) dw, respectively. Several ratios between parent
      polycyclic aromatic hydrocarbons showed that the sources of hydrocarbons in the
      sediments were generally more pyrolytic than petrogenic. The sum of seven PCB
      contents ranged from 0.03 to 13.13 MUg kg(-1) dw. Higher levels of PCBs were
      detected in sediments from the northern parts of the Berre lagoon (stations B1
      and B3). Total pesticides contents ranged from 0.02 to 7.15 MUg kg(-1) dw. Among
      these compounds, ?DDE and ?DDT contents ranged, respectively, from 0.35 to 1.65
      and from 0.37 to 1.52 MUg kg(-1) dw. However, PAH and PCB levels are not high
      enough to be a threat to aquatic organisms and human beings. Total PAH levels
      were below the effects range low (ERL) of 3500 MUg kg(-1) dw. For PCBs, only two
      stations (B1 and B3) are higher than the effect range median (ERM) of 180 MUg kg(
      1) dw. For endrin (pesticide), the concentrations are between the ERL (0.02 MUg
      kg(-1) dw) and the ERM (45 MUg kg(-1) dw).

PMID- 26311269
TI  - Exploring spatial patterns of farmland transactions and farmland use changes.
AB  - Strong economic incentives stimulate the conversion of farmland to non-farm uses
      possessing higher economic benefits, and rising land values can result in further
      conversions in the surrounding areas. However, previous studies focused
      exclusively on the analysis of attribute data, without concern for location or
      geographic information. Our study focuses on the application of spatial analysis
      method by exploring the magnitude and patterns of farmland use changes and
      farmland transactions in Tainan County in southwestern Taiwan. The results show
      that farmland use changes and transactions appear to cluster in specific
      locations-near urban planning areas, industrial parks, and science parks.
      Clustered farmland use changes indicate both excessive development of some
      farmland and possible protection of other farmland, while clustered farmland
      transactions indicate potential pressure for future conversion to non-farming
      uses. Overall, the spatial analyses indicate (without necessarily implying a
      cause-and-effect relationship) that the greater the farmland use change, the
      greater the number of farmland transactions. This approach to exploring the
      spatial patterns in and the interaction between farmland use change and farmland
      transactions can be applied to other regions facing increasing competition for
      farmland conversions and may be a useful tool for monitoring both urban expansion
      and increased farmland transactions. These occurrences should be closely
      monitored by governments to avoid excessive loss of farmland. 

PMID- 26311271
TI  - Drug Oxidation by Cytochrome P450BM3 : Metabolite Synthesis and Discovering New
      P450 Reaction Types.
AB  - There is intense interest in late-stage catalytic C-H bond functionalization as
      an integral part of synthesis. Effective catalysts must have a broad substrate
      range and tolerate diverse functional groups. Drug molecules provide a good test
      of these attributes of a catalyst. A library of P450BM3 mutants developed from
      four base mutants with high activity for hydrocarbon oxidation produced human
      metabolites of a panel of drugs that included neutral (chlorzoxazone,
      testosterone), cationic (amitriptyline, lidocaine) and anionic (diclofenac,
      naproxen) compounds. No single mutant was active for all the tested drugs but
      multiple variants in the library showed high activity with each compound. The
      high conversions enabled full product characterization that led to the discovery
      of the new P450 reaction type of oxidative decarboxylation of an alpha-hydroxy
      carboxylic acid and the formation a protected imine from an amine, offering a
      novel route to alpha-functionalization of amines. The substrate range and varied
      product profiles suggest that this library of enzymes is a good basis for
      developing late-stage C-H activation catalysts.

PMID- 26311270
TI  - Multimorbidity and Risk of Mild Cognitive Impairment.
AB  - OBJECTIVES: To determine the association between multiple chronic conditions and
      risk of incident mild cognitive impairment (MCI) and dementia. DESIGN:
      Prospective cohort study. SETTING: Olmsted County, Minnesota. PARTICIPANTS:
      Cognitively normal individuals (N = 2,176) enrolled in the Mayo Clinic Study of
      Aging (MCSA). MEASUREMENTS: Participants were randomly selected from the
      community, evaluated by a physician, and underwent neuropsychometric testing at
      baseline and at 15-month intervals to assess diagnoses of MCI and dementia.
      Information on International Classification of Diseases, Ninth Revision codes for
      chronic conditions in the 5 years before enrollment was electronically captured
      using the Rochester Epidemiology Project medical records linkage system.
      Multimorbidity was defined as having two or more chronic conditions, and the
      association between multimorbidity and MCI and dementia was examined using Cox
      proportional hazards models. RESULTS: Of 2,176 cognitively normal participants
      (mean age +/- standard deviation 78.5 +/- 5.2; 50.6% male), 1,884 (86.6%) had
      multimorbidity. The risk of MCI or dementia was higher in persons with
      multimorbidity (hazard ratio (HR) = 1.38, 95% confidence interval (CI) = 1.05
      1.82) than in those with one or no chronic condition. The HR was of greater
      magnitude in persons with four or more conditions (HR = 1.61, 95% CI = 1.21-2.13)
      than in those with two or three conditions (HR = 1.03, 95% CI = 0.76-1.39) and
      for men with multimorbidity(HR = 1.53, 95% CI = 1.01-2.31) than for women with
      multimorbidity (HR = 1.20, 95% CI = 0.83-1.74), compared to those with one or no
      chronic condition. CONCLUSION: In older adults, having multiple chronic
      conditions is associated with greater risk of MCI and dementia. This is
      consistent with the hypothesis that multiple etiologies may contribute to MCI and
      late-life dementia. Preventing chronic diseases may be beneficial in delaying or
      preventing MCI and dementia.

PMID- 26311272
TI  - Degradation of the anticancer drug erlotinib during water chlorination: Non
      targeted approach for the identification of transformation products.
AB  - Erlotinib is a highly potent tyrosine kinase inhibitor used in the treatment of
      the most common type of lung cancer. Due to its recent introduction, very scarce
      information is available on its occurrence, environmental fate and toxicological
      effects on aquatic organisms. During chlorination processes normally carried out
      in wastewater treatment plants and in the pretreatment of hospital effluents,
      chlorinated transformation products can be formed with an enhanced toxicity
      relative to the parent compound. Thus, the reactivity of the cytostatic drug
      erlotinib in free chlorine-containing water was investigated for the first time
      in the present work. A non-targeted screening approach based on the use of
      differential profiling tools was applied in order to reveal its potential
      transformation products. Structural elucidation of the detected transformation
      products was performed by ultra-performance liquid chromatography coupled to high
      resolution hybrid quadrupole-Orbitrap tandem mass spectrometry. The proposed
      approach allowed detecting a total of nineteen transformation products, being
      eighteen of them described for the first time in this work, which demonstrates
      its potential in environmental analysis. Among them, six compounds presented
      chlorine atoms in their structures, which may be of major concern. Other
      transformation products involved hydroxylation and oxidation reactions. Time
      course profiles of erlotinib and its transformation products were followed in
      real wastewater samples under conditions that simulate wastewater disinfection.
      Although the structures of these transformation products could not be positively
      confirmed due to lack of standards, their chemical formulas and product ions can
      be added to databases, which will allow their screening in future monitoring
      studies. 

PMID- 26311273
TI  - Metallic iron for environmental remediation: A review of reviews.
AB  - This article critically evaluates recent review articles on using metallic iron
      (Fe(0)) for environmental remediation in order to provide insight for more
      efficient Fe(0)-based systems. The presentation is limited to peer-reviewed
      articles published during 2014 and 2015, excluding own contributions, dealing
      mostly with granular Fe(0). A literature search was conducted up to June 15th
      2015 using Science Direct, SCOPUS, Springer and Web of Science databases. The
      search yielded eight articles that met the final inclusion criteria. The
      evaluation clearly shows that seven articles provide a narrative description of
      processes occurring in the Fe(0)/H20 system according to the concept that Fe(0)
      is a reducing agent. Only one article clearly follows a different path,
      presenting Fe(0) as a generator of adsorbing (hydroxides, oxides) and reducing
      (Fe(II), H/H2) agents. The apparent discrepancies between the two schools are
      identified and extensively discussed based on the chemistry of the Fe(0)/H20
      system. The results of this evaluation indicate clearly that research on 'Fe(0)
      for environmental remediation' is in its infancy. Despite the current paucity of
      reliable data for the design of efficient Fe(0)-based systems, this review
      demonstrates that sensible progress could be achieved within a short period of
      time, specific recommendations to help guide future research are suggested. 

PMID- 26311274
TI  - Extreme weather events: Should drinking water quality management systems adapt to
      changing risk profiles?
AB  - Among the most widely predicted and accepted consequences of global climate
      change are increases in both the frequency and severity of a variety of extreme
      weather events. Such weather events include heavy rainfall and floods, cyclones,
      droughts, heatwaves, extreme cold, and wildfires, each of which can potentially
      impact drinking water quality by affecting water catchments, storage reservoirs,
      the performance of water treatment processes or the integrity of distribution
      systems. Drinking water guidelines, such as the Australian Drinking Water
      Guidelines and the World Health Organization Guidelines for Drinking-water
      Quality, provide guidance for the safe management of drinking water. These
      documents present principles and strategies for managing risks that may be posed
      to drinking water quality. While these principles and strategies are applicable
      to all types of water quality risks, very little specific attention has been paid
      to the management of extreme weather events. We present a review of recent
      literature on water quality impacts of extreme weather events and consider
      practical opportunities for improved guidance for water managers. We conclude
      that there is a case for an enhanced focus on the management of water quality
      impacts from extreme weather events in future revisions of water quality guidance
      documents. 

PMID- 26311275
TI  - Cumulative Evidence That Mesenchymal Stem Cells Promote Healing of Perianal
      Fistulas of Patients With Crohn's Disease--Going From Bench to Bedside.

PMID- 26311276
TI  - TPMT Testing Before Starting Azathioprine or Mercaptopurine: Surely Just Do It?

PMID- 26311277
TI  - MicroRNAs as Therapeutic Targets in Colitis and Colitis-Associated Cancer: Tiny
      Players With a Giant Impact.

PMID- 26311278
TI  - Education Becomes Social: The Intersection of Social Media and Medical Education.

PMID- 26311279
TI  - Sensitization to milk, egg and peanut from birth to 18 years: A longitudinal
      study of a cohort at risk of allergic disease.
AB  - BACKGROUND: Longitudinal data on the natural history of food sensitization beyond
      early childhood are scarce. We aimed to investigate the natural history of milk,
      egg and peanut sensitization from infancy to 18 years and assess whether early
      food sensitization predicted adolescent food allergy. METHODS: Sensitization to
      cow's milk, hen's egg and peanut was measured by skin prick testing at ages 6
      months, 1, 2, 12 and 18 years in a high-risk allergy birth cohort (n = 620).
      Generalized additive models investigated interactions with sex, eczema and
      aeroallergen sensitization in infancy. Logistic regression assessed the
      relationships between early food sensitization and adolescent sensitization and
      probable food allergy up to 18 years. RESULTS: The prevalence of egg and peanut
      sensitization peaked at 12 months, while milk sensitization peaked at both 1 and
      12 years. Boys with early eczema had the highest prevalences of milk and egg
      sensitization throughout follow-ups. However, neither sex nor eczema influenced
      the prevalence of peanut sensitization over time. New onset food sensitization
      beyond the age of 2 was observed in 7% of participants. Food sensitization at 12
      months was associated with increased risk of adolescent food sensitization and
      adolescent probable food allergy, with sensitization to more than one food
      allergen had the strongest predictor. CONCLUSIONS: Food sensitization prevalence
      is highest in infancy and declines after 12 months of age. Boys with early-life
      eczema have the highest prevalence of milk and egg sensitization. Food
      sensitization at 12 months can predict children at greater risk of adolescent
      sensitization and probable food allergy at 12 and 18 years.

PMID- 26311280
TI  - Mode of delivery after obstetric anal sphincter injury.
AB  - OBJECTIVE: To assess the effect of vaginal delivery and caesarean section on
      faecal symptoms and structure and function of anal sphincter in women who
      sustained obstetric anal sphincter injuries (OASIS) in their previous pregnancy
      and were advised about the mode of delivery based on faecal incontinence
      symptoms, anal manometry and endoanal ultrasound. STUDY DESIGN: It is a
      descriptive study on a cohort of women who had OASIS from 2006 to 2013. They were
      assessed after OASIS and during subsequent pregnancy with a questionnaire,
      endoanal ultrasound and anal manometry. Vaginal delivery was recommended to
      asymptomatic women with normal investigations. Elective caesarean section was
      recommended to women with faecal symptoms, anal sphincter defects of more than 30
      degrees  or low resting or incremental anal pressures. All women were reassessed
      after subsequent delivery. RESULTS: Fifty women who had pregnancies after OASIS,
      were seen after OASIS, during subsequent pregnancy and after the second delivery.
      15 women had faecal symptoms after OASIS. The external, internal and combined
      anal sphincter defects were seen in 13, 11 and 9 women respectively. Low resting
      and incremental pressure were seen in 15 and 11 women respectively. Caesarean
      section was done in 22 women and 28 women delivered vaginally. Worsening of
      faecal symptoms and reduction in anal pressures were not observed in planned
      vaginal delivery or elective caesarean section groups. Faecal symptoms were worse
      with reduced anal pressures in three women from the planned caesarean section
      group. One of the women had a vaginal delivery and two women had emergency
      caesarean section at 7cm and 10cm dilatation. There were no new sphincter defects
      or recurrent OASIS in any of the women in the study group. CONCLUSION: Decision
      about the mode of delivery of pregnancy after OASIS based on symptoms, anal
      manometry and endoanal ultrasound helps in preserving the anal sphincter function
      and avoiding unnecessary caesarean sections. Further follow-up of these patients
      is essential to evaluate the long-term effects of this decision.

PMID- 26311281
TI  - Understanding the genetic architecture of complex traits using the function
      valued approach.

PMID- 26311282
TI  - An introduction to synthetic biology in plant systems: ERASynBio/OpenPlant summer
      school for early career researchers, September 2014.

PMID- 26311283
TI  - Anne Osbourn.

PMID- 26311284
TI  - Identification and expression analysis of a heat-shock protein 70 gene in
      Polycelis sp.
AB  - Heat-shock protein 70 (HSP70) is ubiquitously found in a variety of organisms and
      plays an important role in cytoprotection, environmental monitoring, and disease
      resistance. In this study, the full-length complementary DNA (cDNA) of hsp70 from
      planarian Polycelis sp. was first cloned using rapid amplification of cDNA ends
      (RACE). The expression levels of Pyhsp70 were analyzed in the presence of various
      stressors by real-time PCR, and its temporal-spatial expression patterns were
      also examined in both intact and regenerative animals by whole-mount in situ
      hybridization. The results show that (1) the deduced amino acid sequence of
      Pyhsp70 includes three typical HSP70 family signature motifs and is highly
      conserved during evolution; (2) Pyhsp70 expression is induced by prolonged
      starvation, tissue damage, and ionic liquid but inhibited by high or low
      temperatures; and (3) Pyhsp70 mRNA is mainly expressed in the head peripheral
      region and in the regenerating blastema during regeneration. These results
      suggest that the highly expressed Pyhsp70 gene may contribute to enhance
      cytoprotection and tolerance against stress-induced molecular damage, and the
      migration of neoblasts to the wound, which might also be involved in the
      proliferation and differentiation of neoblasts. Our work provides basic data for
      the study of stress responses and regenerative mechanism in freshwater
      planarians. 

PMID- 26311285
TI  - Clinical supervision of allied health professionals in country South Australia: A
      mixed methods pilot study.
AB  - INTRODUCTION: Recent times have witnessed dramatic changes in health care with
      overt recognition for quality and safety to underpin health care service
      delivery. In addition to systems-wide focus, the importance of supporting and
      mentoring people delivering the care has also been recognised. This can be
      achieved through quality clinical supervision. In 2010, Country Health South
      Australia Local Health Network developed a holistic allied health clinical
      governance structure, which was implemented in 2011. OBJECTIVE: This research
      reports on emergent findings from the evaluation of the clinical governance
      structure, which included mandating clinical supervision for all allied health
      staff. METHODS: A mixed method approach was chosen with evaluation of the impact
      of clinical supervision undertaken by a psychometrically sound instrument
      (Manchester Clinical Supervision Scale 26-item version), collected through an
      anonymous online survey and qualitative data collected through semistructured
      interviews and focus groups. RESULTS: Overall, 189 allied health professionals
      responded to the survey. Survey responses indicated allied health professionals
      recognised the importance of and valued receiving clinical supervision (normative
      domain), had levels of trust and rapport with, and were supported by supervisors
      (restorative domain) and positively affected their delivery of care and
      improvement in skills (formative domain). Qualitative data identified enablers
      such as profession specific gains, improved opportunities and consistency for
      clinical supervision and barriers such as persistent organisational issues, lack
      of clarity (delineation of roles) and communication issues. CONCLUSION: The
      findings from this research highlight that while clinical supervision has an
      important role to play, it is not a panacea for all the ills of the health care
      system.

PMID- 26311286
TI  - Displaced Posterior Cruciate Ligament Avulsion Fractures: A Retrospective
      Comparative Study Between Open Posterior Approach and Arthroscopic Single-Tunnel
      Suture Fixation.
AB  - PURPOSE: To retrospectively compare the clinical outcomes of displaced tibial
      side posterior cruciate ligament (PCL) avulsion fractures treated with open
      reduction and screw fixation versus arthroscopic suture fixation. METHODS: From
      2005 to 2013, all displaced PCL tibial-side avulsion fractures treated surgically
      initially by an open posterior approach and later by arthroscopic-assisted suture
      fixation-were retrospectively reviewed. The cases with radiographic evidence of
      greater than 3 mm of displacement and/or grade II or III laxity on the posterior
      drawer test were included in the study group. The associated injuries were duly
      treated. A conservative rehabilitation protocol was followed until radiologic
      fracture union occurred. The patients' clinicoradiologic assessment data at 1
      year of follow-up were used for comparison between the open and arthroscopic
      groups. RESULTS: Forty-seven patients were available with 1 year of follow-up: 27
      in the open group and 20 in the arthroscopic group. More than 90% of patients in
      both groups rated their knee function as normal or nearly normal. At 1 year of
      follow-up, knee function in terms of the Lysholm score (mean of 95.3 with 95%
      confidence interval [CI] 92.85 to 97.75 in open group and mean of 94.8 with 95%
      CI 91.38 to 98.22 in arthroscopic group; P = .812), Tegner activity level (mean
      of 6.8 with 95% CI 6.16 to 7.44 in open group and mean of 7.0 with 95% CI 6.44 to
      7.66 in arthroscopic group, P = .677), International Knee Documentation Committee
      evaluation, and 1-leg hop test was comparable in both groups. The postoperative
      arthrometric laxity measurements with a KT-2000 arthrometer (MEDmetric, San
      Diego, CA) were better in the arthroscopic group, with 0 to 3 mm of laxity in 85%
      of cases in the arthroscopic group versus 74% in the open group. Avulsed fracture
      fragments were usually united by 3 months after surgery. No significant
      complication was noted. CONCLUSIONS: Both arthroscopic and open methods of
      treatment for PCL tibial-side avulsion injuries resulted in comparably good
      clinical outcomes, radiologic healing, and stable knees at short-term follow-up.
      LEVEL OF EVIDENCE: Level III, retrospective comparative study.

PMID- 26311287
TI  - Sodium tanshinone II A sulfonate ameliorates microcirculatory disturbance of
      small intestine by attenuating the production of reactie oxygen species in rats
      with sepsis.
AB  - OBJECTIVE: To examine whether sodium tanshinone II A sulfonate (STS), the main
      effective component of Salvia miltiorrhiza is effective in relieving the
      microcirculatory disturbance of small intestine by suppressing the production of
      reactive oxygen species (ROS) in rats with sepsis. METHODS: A rat model of sepsis
      was induced by cecal ligation and puncture (CLP). Rats (n =40) were randomly
      divided into 4 groups: sham-operated group (sham, n =10), sepsis group (CLP, n
      =10), STS treatment group (STS, n =10) and ROS scavenger dimethylthiourea (DMTU,
      n =10) group. Animals in the STS group were injected with STS (1 mg/kg) for 10
      min through the right external jugular vein after the CLP operation, and animals
      in the CLP group were given the same volume of normal saline after the CLP
      operation. Animals in the DMTU group were intraperitoneally injected with 5 mL/kg
      of 20% DMTU 1 h before CLP. The histopathologic changes in the intestinal tissues
      and changes of mesenteric microcirculation were observed. The levels of ROS in
      intestinal tissues from each group were qualitatively evaluated using a
      fluorescent microscope. The expressions of apoptosis signal-regulating kinase
      (ASK1), phosphorylated ASK1 (phospho-ASK1), p38 mitogen-activated protein kinases
      (p38 MAPK), phosphorylated p38 MAPK (phospho-p38 MAPK) and tissue factor (TF)
      were determined by Western blotting. RESULTS: It was shown that there were
      obvious microcirculatory disturbance (P <0.05) and tissue injuries in intestinal
      tissues after CLP operation. The levels of ROS production, phospho-ASK1, phospho
      p38 MAPK and TF were increased. Both STS and DMTU suppressed ROS, phospho-ASK1,
      phospho-p38 MAPK and TF production, and ameliorated the microcirculatory
      disturbance and tissues injury (P <0.01). CONCLUSION: STS can ameliorate the
      microcirculatory disturbance of the small intestine by attenuating the production
      of ROS in rats with sepsis.

PMID- 26311288
TI  - The standardization of acupuncture treatment for radiation-induced xerostomia: A
      literature review.
AB  - OBJECTIVE: To assess the relative standardization of acupuncture protocols for
      radiation-induced xerostomia. METHODS: A literature search was carried out up to
      November 10, 2012 in the databases PubMed/MEDLINE, EMBASE and China National
      Knowledge Infrastruction with the terms: radiation-induced xerostomia,
      acupuncture, acupuncture treatment, and acupuncture therapy. Five ancient Chinese
      classic acupuncture works were also reviewed with the keywords "dry mouth,
      thirst, dry tongue, dry eyes and dry lips" to search the effective acupuncture
      points for dry mouth-associated symptoms in ancient China. RESULTS: Twenty-two
      full-text articles relevant to acupuncture treatment for radiation-induced
      xerostomia were included and a total of 48 acupuncture points were searched in
      the 5 ancient Chinese classic acupuncture works, in which the most commonly used
      points were Chengjiang (CV24), Shuigou (GV 26), Duiduan (GV 27), Jinjin (EX-HN
      12), and Yuye (EX-HN 13) on head and neck, Sanjian (LI 3), Shangyang (LI 1),
      Shaoshang (LU 11), Shaoze (SI 1), Xialian (LI 8) on hand, Fuliu (KI 7), Dazhong
      (KI 4), Zuqiaoyin (GB 44), Taichong (LR 3), Zhaohai (KI 6) on foot, Burong (ST
      19), Zhangmen (LR 13), Tiantu (CV 22), Qimen (LR 14) on abdomen, Feishu (BL 13),
      Danshu (BL 19), Xiaochaogshu (BL 27), Ganshu (BL 18) on back, Shenmen (TF 4),
      Shen (CO10, Kidney), Yidan (CO11, Pancreas) and Pi (CO13, Spleen) on ear.
      CONCLUSION: There were considerable heterogeneities in the current acupuncture
      treatment protocols for radiation-induced xerostomia. Based on the results of the
      review and the personal perspectives, the authors provide a recommendation for
      manual acupuncture protocols in treating radiationinduced xerostomia patients
      with head and neck cancer.

PMID- 26311289
TI  - Adherence to Anticoagulant Therapy in Pediatric Patients Hospitalized With
      Pulmonary Embolism or Deep Vein Thrombosis: A Retrospective Cohort Study.
AB  - OBJECTIVES: The American College of Chest Physicians recommends anticoagulant
      therapy for at least 3 months in children hospitalized for venous
      thromboembolism. The objectives of the study were to evaluate the medication
      utilization patterns and predictors of adherence to anticoagulant therapy in
      pediatric population. METHODS: Texas Medicaid medical and prescription claims
      from September 1, 2007 to December 12, 2012 were extracted for children (<18
      years) hospitalized for pulmonary embolism (PE) or deep vein thrombosis (DVT).
      The index date was defined as the date of the first prescription of an
      anticoagulant given within 14 days of discharge. Proportion of days covered
      (>=80% vs <80%) was used to assess adherence to anticoagulants while controlling
      for demographics, cause of hospitalization, history of nonsteroidal anti
      inflammatory drug use, anticoagulant use, malignancy, drug type, and Charlson
      comorbidity index (CCI). KEY FINDINGS: The patients (n = 60) had a mean (+/-
      standard deviation [SD]) age of 14.2 (+/-4.8) years, were primarily female
      (56.7%), African American (55.0%), enoxaparin users (58.3%), and had a mean (+/
      SD) CCI of 18.3 (+/-37.7). The mean (+/-SD) adherence rates for warfarin and
      enoxaparin were 85.5% (+/-22.7%) and 78.7% (+/-27.8%), respectively. Overall,
      66.7% were adherent (>=80%) to anticoagulant therapy. Logistic regression showed
      that increasing age was significantly associated with adherence to anticoagulant
      therapy, after controlling for other covariates (odds ratio = 1.5, 95% confidence
      interval = 1.13-1.85). CONCLUSION: Nearly one-third of the pediatric patients on
      anticoagulant therapy after discharge from PE or DVT were still nonadherent.
      Further research is needed to highlight the factors responsible for nonadherence
      in pediatric patients.

PMID- 26311291
TI  - Stepped gradients on polymeric monolithic columns by photoinitiated grafting.
AB  - The surface of polymethacrylate monoliths was functionalized by a post
      polymerization modification, by means of a novel photo-initiated graft procedure
      where the charged monomer, sulfopropyl methacrylate, was controllably grafted
      stepwise, i.e. with incremental graft energies. The grafting approach was
      optimized using scanning capacitively coupled contactless conductivity detection.
      The effect of the localized ion exchange capacity and resultant gradient
      stationary phase upon ion-exchange chromatographic retention, selectivity, and
      performance was investigated, and compared to a homogeneously grafted (isotropic)
      column. The gradient column provided reduced peak widths at half height for both
      cationic analytes, with a reduction of 34 and 33%, respectively, when compared to
      the isotropic column. 

PMID- 26311290
TI  - Optical control of NMDA receptors with a diffusible photoswitch.
AB  - N-methyl-D-aspartate receptors (NMDARs) play a central role in synaptic
      plasticity, learning and memory, and are implicated in various neuronal
      disorders. We synthesized a diffusible photochromic glutamate analogue,
      azobenzene-triazole-glutamate (ATG), which is specific for NMDARs and functions
      as a photoswitchable agonist. ATG is inactive in its dark-adapted trans-isoform,
      but can be converted into its active cis-isoform using one-photon (near UV) or
      two-photon (740 nm) excitation. Irradiation with violet light photo-inactivates
      ATG within milliseconds, allowing agonist removal on the timescale of NMDAR
      deactivation. ATG is compatible with Ca(2+) imaging and can be used to optically
      mimic synaptic coincidence detection protocols. Thus, ATG can be used like
      traditional caged glutamate compounds, but with the added advantages of NMDAR
      specificity, low antagonism of GABAR-mediated currents, and precise temporal
      control of agonist delivery. 

PMID- 26311292
TI  - Subacute combined degeneration of the spinal cord in an adolescent male with
      avoidant/restrictive food intake disorder: A clinical case report.
AB  - Avoidant/restrictive food intake disorder (ARFID) is a potentially lethal eating
      disorder. This case example of a male, G, aged 17 years with ARFID illustrates
      the multiplicity of health problems related to nutritional deficiencies which may
      develop in an adolescent of normal weight. Of particular concern was the
      diagnosis of subacute combined degeneration (SCD) of the spinal cord and the real
      possibility that G may have irreversible damage to his spinal cord. To our
      knowledge, this is the first reported case of a patient with SCD of the spinal
      cord due to ARFID. The adolescent was found to be deficient in Vitamin A, E, K,
      D, B12, and folate. Management required vitamin replacement, initial nasogastric
      feeding and the slow introduction of a varied diet. This patient will require
      long term rehabilitation. Medical practitioners need to be attuned to abnormal
      eating patterns in children and adolescents and refer for specialist care early.

PMID- 26311293
TI  - Use of PocketMaker Microkeratome for Creation of Corneal Pocket for Foldable
      Keratoprosthesis KeraKlear Implantation - Case Series.
AB  - PURPOSE: To describe a surgical method for corneal pocket creation for KeraKlear
      keratoprosthesis implantation by PocketMaker microkeratome. METHODS: We implanted
      keratoprosthesis KeraKlear in 3 patients. In all cases, we used a microkeratome
      PocketMaker to create a corneal pocket, where the incision was made at a depth of
      300 um with a vibrating diamond blade. RESULTS: Although corneas have been
      extensively opaque and vascularized, in all three cases we successfully performed
      suction of the microkeratome system and created a corneal pocket without any
      difficulties. Subsequent keratoprosthesis implantations were performed without
      any problems. CONCLUSION: The technique is simple, relatively cheap, and the
      creation of the corneal pocket is possible even in patients with vascularized and
      opaque cornea.

PMID- 26311294
TI  - Bad vessels beware! Semaphorins will sort you out!

PMID- 26311295
TI  - Acute hypercarbia increases the lower limit of cerebral blood flow autoregulation
      in a porcine model.
AB  - OBJECTIVES: In the present study, our objective was to determine if hypercarbia
      would alter cerebral blood flow (CBF) autoregulation and reduce the ability of
      cerebrovascular reactivity monitoring to identify the lower limit of
      cerebrovascular autoregulation (LLA). METHODS: Anaesthetised juvenile pigs were
      assigned between two groups: normocarbia (control group, n = 10) or hypercarbia
      [high carbon dioxide (CO2) group, n = 8]. Normocarbia subjects were maintained
      with an arterial CO2 of 40 Torr, while the hypercarbia subjects had an increase
      of inspired CO2 to achieve an arterial pCO2 of >80 Torr. Gradual hypotension was
      induced by continuous haemorrhage from a catheter in the femoral vein, and the
      LLA was determined by monitoring cortical laser Doppler flux (LDF). Vascular
      reactivity monitoring was performed using the pressure reactivity index (PRx) and
      haemoglobin volume index (HVx). RESULTS: There were no sustained differences in
      ICP between groups. Autoregulation was present in both groups, despite elevation
      in pCO2.The control group had an average LLA of 45 mmHg (95% CI: 43-47 mmHg) and
      the high CO2 group had a LLA of 75 mmHg (95% CI: 73-77 mmHg). The detected LLA
      for each subject correlated with the level of pCO2 (spearman R = 0.8243, P <
      0.0001). Both the PRx and HVx accurately detected the LLA despite the presence of
      hypercarbia. DISCUSSION: Hypercarbia without acidosis increases the observed LLA
      independent of alterations in ICP. Elevations in CO2 can impair cerebrovascular
      autoregulation, but if there is a sufficient increase in blood pressure above the
      CO2 altered LLA, then autoregulation persists.

PMID- 26311296
TI  - List of primary types of the larentiine moth species (Lepidoptera: Geometridae)
      described from Indonesia - a starting point for biodiversity assessment of the
      subfamily in the region.
AB  - BACKGROUND: The Indonesian geometrid moth fauna is rich and diverse, yet it is
      poorly studied. This is particularly the case for the second largest geometrid
      subfamily Larentiinae which comprises moths with predominantly high mountainous
      distribution in the tropics. The present study provides a first inventory of the
      primary type specimens of larentiine moth species (Lepidoptera: Geometridae)
      described from Indonesia. NEW INFORMATION: The list of species described from
      Indonesia is arranged alphabetically by the tribe, genus, and species, and
      presents data on 251 species and subspecies. For each species type status, type
      locality, depository, and a full reference to the original description are
      listed. Synonyms with Indonesian type localities are included. The study
      indicates a large part of the Indonesian geometrid fauna belong to the tribe
      Eupitheciini.

PMID- 26311297
TI  - Ratio of fetal anteroposterior to transverse cerebellar diameter for detection of
      the cerebellar hypoplasia in the second trimester and comparison with trisomy 18.
AB  - AIM: Cerebellar hypoplasia, particularly, trisomy 18, represents a chromosomal
      abnormality. However, morphological assessment of the fetal cerebellum is yet to
      be established. The purpose of this study was to produce reference values for the
      fetal transverse cerebellar diameter (TCD), anteroposterior cerebellar diameter
      (APCD) and the ratio of APCD to TCD (APCD/TCD ratio) in normal fetuses, compared
      with cases of trisomy 18. METHODS: This retrospective study included 266 normal
      singleton pregnancies resulting in term delivery at our institution from 2012
      2013. Patients had received ultrasound examinations in the second trimester. TCD
      and APCD measurements were performed and then APCD/TCD ratio was calculated.
      Consequently, three cases of trisomy 18 were compared with reference values.
      RESULTS: Gestational age correlated with TCD (rs  = 0.766, P < 0.0001) and APCD
      (rs  = 0.61, P < 0.0001), but not with APCD/TCD ratio (rs  = 0.070, P = 0.252).
      The median APCD/TCD ratio was 0.52 and the standard deviation was 0.05. In cases
      of trisomy 18, all TCD measurements were located within normal ranges. In
      contrast, both the APCD and APCD/ TCD ratio displayed lower values than that of
      normal fetuses. CONCLUSIONS: This study showed that not only TCD but also APCD
      correlated with gestational age, and APCD/TCD ratio indicated a fixed value
      (almost 0.5) in normal fetuses. Furthermore, APCD and APCD/TCD ratio were deemed
      useful indicators for cerebellar hypoplasia. In particular, the APCD/TCD ratio
      proved more convenient, without requiring individual evaluation of TCD and APCD.

PMID- 26311298
TI  - RE: The Effect on Melanoma Risk of Genes Previously Associated With Telomere
      Length.

PMID- 26311299
TI  - Response.

PMID- 26311300
TI  - Erratum: XI-006 induces potent p53-independent apoptosis in Ewing sarcoma.

PMID- 26311301
TI  - Stent graft implantation in an aortic pseudoaneurysm associated with a fractured
      Cheatham-Platinum stent in aortic coarctation.
AB  - We report a case of aortic pseudoaneurysm associated with a fractured bare
      Cheatham-Platinum stent following stenting for aortic coarctation. These
      complications were recognised 6 years after the implantation procedure and were
      successfully managed by percutaneous stent graft implantation. Staged approach
      for stent dilatation might prevent development of aortic pseudoaneurysms. In
      addition, careful follow-up is warranted after stenting for aortic coarctation,
      particularly in patients with recognised aortic wall injury. 

PMID- 26311302
TI  - Induction of tolerance and prolongation of islet allograft survival by syngeneic
      hematopoietic stem cell transplantation in mice.
AB  - BACKGROUNDS: Syngeneic or autologous hematopoietic stem cells transplantation
      (HSCT) has been proposed to treat autoimmune diseases because of its
      immunosuppressive and immunomodulatory effects, which can also contribute to
      posttransplant antirejection therapy. In this study, we explored the tolerogenic
      effect of syngeneic HSCT on prolonging islet allograft survival. METHODS: C57BL/6
      mice received syngeneic HSCT plus preconditioning with sublethal irradiation.
      Then islets of BALB/c mice were transplanted into the renal subcapsular of
      C57BL/6 mice after chemically induced into diabetes. RESULTS: HSCT mice exhibited
      improved islet allograft survival and increased serum insulin compared to control
      mice. Islet allografts of HSCT mice displayed lower level lymphocyte infiltration
      and stronger insulin staining than control mice. T cells of HSCT mice
      proliferated poorly in response to allogeneic splenocytes compared to control
      mice. Mice appeared reversed interferon-gamma (IFN-gamma)/interleukin-4 (IL-4)
      ratio to a Th2 immune deviation after syngeneic HSCT. The percentage of CD8(+) T
      cells was lower, while percentage of CD4(+)CD25(+)Foxp3(+) T regulatory cells
      (Tregs) was higher in HSCT mice than control mice. HSCT mice showed higher
      percentage of CTLA-4(+) T cells and expression of CTLA-4 mRNA than control mice.
      Targeting of CTLA-4 by intraperitoneal injection of anti-CTLA-4 mAb abrogated the
      effect of syngeneic HSCT on prolonging islet allograft survival, inhibiting
      activity of T cells in response to alloantigen, promoting Th1 to Th2 immune
      deviation and up regulating CD4(+)CD25(+)Foxp3(+) Tregs. CONCLUSIONS: Syngeneic
      HSCT plus preconditioning of sublethal irradiation induces tolerance and improves
      islet allograft survival in fully mismatched mice model. Th1 to Th2 immune
      deviation, increased CD4(+)CD25(+)Foxp3(+) Tregs and up-regulation of CTLA-4
      maybe contribute to the tolerogenic effect induced by syngeneic HSCT.

PMID- 26311303
TI  - A sea anemone-like CuO/Co3O4 composite: an effective catalyst for electrochemical
      water splitting.
AB  - A facile unipolar pulse electrodeposition combined with the thermal oxidation
      method was applied for fabrication of CuO/Co3O4 composites on carbon electrode
      for water electrolysis, and it was found that the sea anemone-like one with a 3D
      hierarchical structure formed at -0.8 V exhibited excellent performance for water
      electrolysis at a low overpotential with high stability. 

PMID- 26311304
TI  - Homogeneous nucleation and microstructure evolution in million-atom molecular
      dynamics simulation.
AB  - Homogeneous nucleation from an undercooled iron melt is investigated by the
      statistical sampling of million-atom molecular dynamics (MD) simulations
      performed on a graphics processing unit (GPU). Fifty independent instances of
      isothermal MD calculations with one million atoms in a quasi-two-dimensional cell
      over a nanosecond reveal that the nucleation rate and the incubation time of
      nucleation as functions of temperature have characteristic shapes with a nose at
      the critical temperature. This indicates that thermally activated homogeneous
      nucleation occurs spontaneously in MD simulations without any inducing factor,
      whereas most previous studies have employed factors such as pressure, surface
      effect, and continuous cooling to induce nucleation. Moreover, further
      calculations over ten nanoseconds capture the microstructure evolution on the
      order of tens of nanometers from the atomistic viewpoint and the grain growth
      exponent is directly estimated. Our novel approach based on the concept of
      "melting pots in a supercomputer" is opening a new phase in computational
      metallurgy with the aid of rapid advances in computational environments. 

PMID- 26311305
TI  - Looking forward, looking back: capturing drought in flagrante delicto and
      uncovering its broader consequences for forest ecosystems.

PMID- 26311306
TI  - Validation for histology-driven diagnosis in non-small cell lung cancer using hsa
      miR-205 and hsa-miR-21 expression by two different normalization strategies.
AB  - Targeted therapy of non-small cell lung cancer (NSCLC) demands a more accurate
      tumor classification that is crucial for patient selection in personalized
      treatment. MicroRNAs constitute a promising class of biomarkers and a helpful
      tool for the distinction between lung adenocarcinoma (AC) and squamous cell lung
      carcinoma (SCC). The aim of this study was to evaluate the impact of two
      different normalization strategies, using U6 snRNA and hsa-miR-103 as reference
      genes, on hsa-miR-205 and hsa-miR-21 expression levels, in terms of the
      classification of subtypes of NSCLC. By means of a quantitative real-time
      polymerase chain reaction (qRT-PCR) microRNA expression levels were evaluated in
      a classification set of 98 surgically resected NSCLC fresh-frozen samples, and
      validated findings in an independent set of 42 NSCLC samples. The microRNA
      expression levels were exploited to develop a diagnostic test using two data
      normalization strategies. The performance of microRNA profiling in different
      normalization methods was compared. We revealed the microRNA-based qRT-PCR tests
      to be appropriate measures for distinguishing between AC and SCC (the concordance
      of histologic diagnoses and molecular methods greater than 88%). Performance
      evaluation of microRNA tests, based on the two normalization strategies, showed
      that the procedure using hsa-miR-103 as reference target has a slight advantage
      (sensitivity 83.33 and 100% in classification and validation set, respectively)
      compared to U6 snRNA. Molecular tests based on microRNA expression allow a
      reliable classification of subtypes for NSCLC and can constitute a useful
      diagnostic strategy in patient selection for targeted therapy. 

PMID- 26311307
TI  - Improving postoperative pain management in children by providing regular training
      and an updated pain therapy concept.
AB  - BACKGROUND: In recent years, children's hospitals have increasingly implemented
      postoperative pain management protocols to reduce postoperative pain and improve
      patient satisfaction. The effectiveness and long-term sustainability of such
      protocols have rarely been studied. Therefore, we conducted a prospective
      intervention study to assess the impact of regular training and improvement of
      clinical processes on the quality of postoperative pain management. METHODS: We
      conducted an initial assessment of the status quo of postoperative pain
      management (Audit 1) followed by repeated training and improvement of clinical
      processes (analgesic pocket card, parents' brochure, modification of the patient
      chart, bimonthly advanced trainings sessions) and a follow-up review after 3
      years (Audit 2). We used a data entry form, a patient survey, and an anonymous
      questionnaire for the nursing staff as measurement tools. RESULTS: Our analysis
      included a total of 93 and 85 patients in the initial and final audits. The
      return rates of the nursing staff questionnaire were 83% (Audit 1) and 77% (Audit
      2). The training and process improvements resulted in significant improvement in
      the administration of analgesics for pain requiring treatment, the control of
      pain measurement after the administration of analgesics and the use of non
      pharmacological pain therapies. The patients reported faster administration of
      analgesics for acute pain and improved pain relief following the intervention.
      CONCLUSIONS: Repeated training and improvement of clinical processes can
      significantly improve the long-term quality of postoperative pain management in
      children with a tolerable amount of effort on the part of health care
      professionals and institutions.

PMID- 26311308
TI  - Major hepatectomy for complex liver trauma.
AB  - The liver is the most frequently injured intraperitoneal organ, despite its
      relatively protected location. The liver consisting of a relatively fragile
      parenchyma contained within the Glisson capsule, which is thin and does not
      provide it with great protection. The management of hepatic trauma has undergone
      a paradigm shift over the past several decades with significant improvement in
      outcomes. Shifting from mandatory operation to selective nonoperative treatment,
      and, presently, to nonoperative treatment with selective operation. Operative
      management emphasizes packing, damage control, and utilization of interventional
      radiology, such as angiography and embolization. Because of the high morbidity
      and mortality, liver resection seems to have a minimal role in the management of
      hepatic injury in many reports, but in a specialized referral center, like our
      institute, surgical treatment becomes, in many cases, the only life-saving
      treatment. Innovations in liver transplant surgery, living liver donation, and
      the growth of specialized liver surgery teams have changed the way that surgeons
      and hepatic resection are done. 

PMID- 26311310
TI  - Endothelial-specific deficiency of Junctional Adhesion Molecule-C promotes vessel
      normalisation in proliferative retinopathy.
AB  - In proliferative retinopathies, like proliferative diabetic retinopathy and
      retinopathy of prematurity (ROP), the hypoxia response is sustained by the
      failure of the retina to revascularise its ischaemic areas. Non-resolving retina
      ischaemia/hypoxia results in upregulation of pro-angiogenic factors and
      pathologic neovascularisation with ectopic, fragile neovessels. Promoting
      revascularisation of the retinal avascular area could interfere with this vicious
      cycle and lead to vessel normalisation. Here, we examined the function of
      endothelial junctional adhesion molecule-C (JAM-C) in the context of ROP.
      Endothelial-specific JAM-C-deficient (EC-JAM-C KO) mice and littermate JAM-C
      proficient (EC-JAM-C WT) mice were subjected to the ROP model. An increase in
      total retinal vascularisation was found at p17 owing to endothelial JAM-C
      deficiency, which was the result of enhanced revascularisation and vessel
      normalisation, thereby leading to significantly reduced avascular area in EC-JAM
      C KO mice. In contrast, pathologic neovessel formation was not affected by
      endothelial JAM-C deficiency. Consistent with improved vessel normalisation, tip
      cell formation at the interface between vascular and avascular area was higher in
      EC-JAM-C KO mice, as compared to their littermate controls. Consistently, JAM-C
      inactivation in endothelial cells resulted in increased spreading on fibronectin
      and enhanced sprouting in vitro in a manner dependent on beta1-integrin and on
      the activation of the small GTPase RAP1. Together, endothelial deletion of JAM-C
      promoted endothelial cell sprouting, and consequently vessel normalisation and
      revascularisation of the hypoxic retina without altering pathologic
      neovascularisation. Thus, targeting endothelial JAM-C may provide a novel
      therapeutic strategy for promoting revascularisation and vessel normalisation in
      the treatment of proliferative retinopathies. 

PMID- 26311311
TI  - Remote cerebellar haemorrhage from site of craniotomy: A report of two cases.
AB  - Remote cerebellar haemorrhage (RCH) is a rare complication of neurosurgical
      procedures seldom requiring intervention. We report two cases of RCH. The first
      unilateral RCH is asymptomatic, the other is bilateral and associated with
      supratentorial haemorrhage and hydrocephalus requiring intervention. We propose
      multiple foci of haemorrhage as an adverse prognostic marker in RCH. 

PMID- 26311309
TI  - Weak conservation of structural features in the interfaces of homologous
      transient protein-protein complexes.
AB  - Residue types at the interface of protein-protein complexes (PPCs) are known to
      be reasonably well conserved. However, we show, using a dataset of known 3-D
      structures of homologous transient PPCs, that the 3-D location of interfacial
      residues and their interaction patterns are only moderately and poorly conserved,
      respectively. Another surprising observation is that a residue at the interface
      that is conserved is not necessarily in the interface in the homolog. Such
      differences in homologous complexes are manifested by substitution of the
      residues that are spatially proximal to the conserved residue and structural
      differences at the interfaces as well as differences in spatial orientations of
      the interacting proteins. Conservation of interface location and the interaction
      pattern at the core of the interfaces is higher than at the periphery of the
      interface patch. Extents of variability of various structural features reported
      here for homologous transient PPCs are higher than the variation in homologous
      permanent homomers. Our findings suggest that straightforward extrapolation of
      interfacial nature and inter-residue interaction patterns from template to target
      could lead to serious errors in the modeled complex structure. Understanding the
      evolution of interfaces provides insights to improve comparative modeling of PPC
      structures. 

PMID- 26311312
TI  - Anatomy of a negative feedback loop: the case of IkappaBalpha.
AB  - The magnitude, duration and oscillation of cellular signalling pathway responses
      are often limited by negative feedback loops, defined as an 'activator-induced
      inhibitor' regulatory motif. Within the NFkappaB signalling pathway, a key
      negative feedback regulator is IkappaBalpha. We show here that, contrary to
      current understanding, NFkappaB-inducible expression is not sufficient for
      providing effective negative feedback. We then employ computational simulations
      of NFkappaB signalling to identify IkappaBalpha molecular properties that are
      critical for proper negative feedback control and test the resulting predictions
      in biochemical and single-cell live-imaging studies. We identified nuclear import
      and nuclear export of IkappaBalpha and the IkappaBalpha-NFkappaB complex, as well
      as the free IkappaBalpha half-life, as key determinants of post-induction
      repression of NFkappaB and the potential for subsequent reactivation. Our work
      emphasizes that negative feedback is an emergent systems property determined by
      multiple molecular and biophysical properties in addition to the required
      'activator-induced inhibitor' relationship. 

PMID- 26311313
TI  - Connectivity, passability and heterogeneity interact to determine fish population
      persistence in river networks.
AB  - The movement of fish in watersheds is frequently inhibited by human-made
      migration barriers such as dams or culverts. The resulting lack of connectivity
      of spatial subpopulations is often cited as a cause for observed population
      decline. We formulate a matrix model for a spatially distributed fish population
      in a watershed, and we investigate how location and other characteristics of a
      single movement barrier impact the asymptotic growth rate of the population. We
      find that while population growth rate often decreases with the introduction of a
      movement obstacle, it may also increase due to a 'retention effect'. Furthermore,
      obstacle mortality greatly affects population growth rate. In practice, different
      connectivity indices are used to predict population effects of migration
      barriers, but the relation of these indices to population growth rates in
      demographic models is often unclear. When comparing our results with the
      dentritic connectivity index, we see that the index captures neither the
      retention effect nor the influences of obstacle mortality. We argue that
      structural indices cannot entirely replace more detailed demographic models to
      understand questions of persistence and extinction. We advocate the development
      of novel functional indices and characteristics. 

PMID- 26311314
TI  - Mechanical homeostasis of a DOPA-enriched biological coating from mussels in
      response to metal variation.
AB  - Protein-metal coordination interactions were recently found to function as
      crucial mechanical cross-links in certain biological materials. Mussels, for
      example, use Fe ions from the local environment coordinated to DOPA-rich proteins
      to stiffen the protective cuticle of their anchoring byssal attachment threads.
      Bioavailability of metal ions in ocean habitats varies significantly owing to
      natural and anthropogenic inputs on both short and geological spatio-temporal
      scales leading to large variations in byssal thread metal composition; however,
      it is not clear how or if this affects thread performance. Here, we demonstrate
      that in natural environments mussels can opportunistically replace Fe ions in the
      DOPA coordination complex with V and Al. In vitro removal of the native DOPA
      metal complexes with ethylenediaminetetraacetic acid and replacement with either
      Fe or V does not lead to statistically significant changes in cuticle
      performance, indicating that each metal ion is equally sufficient as a DOPA cross
      linking agent, able to account for nearly 85% of the stiffness and hardness of
      the material. Notably, replacement with Al ions also leads to full recovery of
      stiffness, but only 82% recovery of hardness. These findings have important
      implications for the adaptability of this biological material in a dynamically
      changing and unpredictable habitat. 

PMID- 26311315
TI  - Predicting cortical bone adaptation to axial loading in the mouse tibia.
AB  - The development of predictive mathematical models can contribute to a deeper
      understanding of the specific stages of bone mechanobiology and the process by
      which bone adapts to mechanical forces. The objective of this work was to
      predict, with spatial accuracy, cortical bone adaptation to mechanical load, in
      order to better understand the mechanical cues that might be driving adaptation.
      The axial tibial loading model was used to trigger cortical bone adaptation in
      C57BL/6 mice and provide relevant biological and biomechanical information. A
      method for mapping cortical thickness in the mouse tibia diaphysis was developed,
      allowing for a thorough spatial description of where bone adaptation occurs.
      Poroelastic finite-element (FE) models were used to determine the structural
      response of the tibia upon axial loading and interstitial fluid velocity as the
      mechanical stimulus. FE models were coupled with mechanobiological governing
      equations, which accounted for non-static loads and assumed that bone responds
      instantly to local mechanical cues in an on-off manner. The presented formulation
      was able to simulate the areas of adaptation and accurately reproduce the
      distributions of cortical thickening observed in the experimental data with a
      statistically significant positive correlation (Kendall's tau rank coefficient
      tau = 0.51, p < 0.001). This work demonstrates that computational models can
      spatially predict cortical bone mechanoadaptation to a time variant stimulus.
      Such models could be used in the design of more efficient loading protocols and
      drug therapies that target the relevant physiological mechanisms. 

PMID- 26311316
TI  - The role of passive avian head stabilization in flapping flight.
AB  - Birds improve vision by stabilizing head position relative to their surroundings,
      while their body is forced up and down during flapping flight. Stabilization is
      facilitated by compensatory motion of the sophisticated avian head-neck system.
      While relative head motion has been studied in stationary and walking birds,
      little is known about how birds accomplish head stabilization during flapping
      flight. To unravel this, we approximate the avian neck with a linear mass-spring
      damper system for vertical displacements, analogous to proven head stabilization
      models for walking humans. We corroborate the model's dimensionless natural
      frequency and damping ratios from high-speed video recordings of whooper swans
      (Cygnus cygnus) flying over a lake. The data show that flap-induced body
      oscillations can be passively attenuated through the neck. We find that the
      passive model robustly attenuates large body oscillations, even in response to
      head mass and gust perturbations. Our proof of principle shows that bird-inspired
      drones with flapping wings could record better images with a swan-inspired
      passive camera suspension. 

PMID- 26311317
TI  - Dendrimers as an Effective Nanocarrier in Cardiovascular Disease.
AB  - In the last two decades, dendrimers have proven their capabilities in drug
      delivery, physical stabilization of the drug, solubility enhancement of the
      poorly soluble drugs and gene delivery. Several key features of dendrimers such
      as excellent control over molecular structure, nanoscopic size, availability of
      multiple functional groups at the periphery and narrow polydispersity index
      distinguish them as a superior choice over available polymers. The diversity of
      bio-actives loaded in dendrimers due to covalent and non-covalent interactions,
      such as hydrogen bonding and hydrophobic interaction contribute to the physical
      forces for binding of bioactives. The key advantage of drug-loaded dendrimers is
      the delayed and sustained-release of bioactives because of the encapsulation of
      the drug in the hydrophobic cavities of the dendrimer that acts as a sink to
      retain the drug molecules for extended duration. Because of these features
      researchers are particularly excited about the potential application of
      dendrimers as a versatile carrier for drug delivery. Collectively, this review
      focuses on detailed note on the delivery and improved solubility of poorly
      soluble anti-cardiovascular bioactives, nitric oxide (NO) donor for anti
      thrombosis, gene delivery and delivery of receptor agonists for cardio-protective
      action of the receptors using dendrimers. 

PMID- 26311318
TI  - MicroRNA-10b promotes migration and invasion through Hoxd10 in human gastric
      cancer.
AB  - BACKGROUND: This study aims to investigate the effect of miR-10b overexpression
      on cancer cell proliferation, migration, invasion, and Hoxd10 expression.
      METHODS: The effect of miR-10b on proliferation, migration, and invasion of MKN
      28, BGC-823, and SGC-7901 cells and the expression of Hoxd10 protein in SGC-7901
      and BGC-823 cells were detected following transfection of miR-10b inhibitor or
      Negative Control B. Expression of Hoxd10 protein in 436 paraffin-embedded cancer
      tissues was also investigated. RESULTS: miR-10b was significantly upregulated in
      AGS, MKN-28, BGC-823, HCG-27, SGC-7901, and MKN-45 cell lines, miR-10b inhibitor
      significantly inhibited proliferation and migration of MKN-45, BGC-823 and SGC
      7901 cells 48 h after transfection, while Hoxd10 protein in these cells lines had
      increased 72 h after transfection. Hoxd10 was highly expressed in gastric cancer
      and correlated with size of tumor, Lauren classification, depth of invasion,
      lymph node and distant metastasis, Tumor-Node-Metastasis (TNM) stage, and
      prognosis. CONCLUSIONS: miR-10b promotes migration and invasion through Hoxd10 in
      human gastric cancer cell lines and may play an important role in tumorigenesis,
      progression, and prognosis.

PMID- 26311319
TI  - Life-threatening coronary disease is prevalent in patients with stenosing carotid
      artery disease.
AB  - BACKGROUND: Atherosclerosis affects several vascular trees systemically and
      though surgical plaque removal diminishes the risk of stroke in patients with
      carotid stenosis, they still face a risk of other atherothrombotic complications
      like myocardial infarction and premature death. AIMS AND/OR HYPOTHESIS: This
      study was designed to reveal the long-term risk of death and atherothrombotic
      events following carotid endarterectomy. METHODS: Eighty-nine previously (1997
      2000) endarterectomized carotid patients (56-92 years) were followed up to 15.2
      years. Causes of death, cardiovascular events (stroke, transient ischemic attack,
      acute myocardial infarction), comorbidities, and medications were recorded and
      analyzed by Cox regression analysis. Four population controls and four controls
      with coronary disease (n = 712) were selected for each case from a population
      cohort for age- and gender-matched analysis. RESULTS: At the end of follow-up, 41
      (44.6%) patients had died and 48 were alive. Ten patients (24,4%) died due to
      acute myocardial infarction and one (2,4%) due to stroke. Nineteen (21%) patients
      had an acute myocardial infarction, 12 (13%) had a stroke, 13 (15%) had a
      transient ischemic attack, and 5 (6%) had other atherothrombotic events. The risk
      of death was 5.7-fold in diabetics (P < 0.001) and 3.9-fold in smokers (P <
      0.001). Patients who did not use statins had 5.0-fold, and irregular users 3.3
      fold risk of death compared with active users (P = 0.005 and P = 0.001,
      respectively). The major factors associated with acute myocardial infarction were
      diabetes (6.0-fold risk, P = 0.004), bilateral carotid disease (3.5-fold risk, P
      = 0.014), and lack of statin use (4.4-fold risk, P = 0.038). Compared with
      population controls, carotid patients had a 4.4-fold risk of acute myocardial
      infarction (P = 0.002). CONCLUSIONS: Endarterectomized carotid patients have a
      high risk of acute myocardial infarction and death, and need an intensified
      cardiovascular disease-risk-lowering treatment. Although asymptomatic, the
      evaluation of prognostically significant myocardial ischemia should be considered
      in these high-risk patients. Eventually, a clinical trial is needed to address
      whether carotid patients would benefit from early intervention.

PMID- 26311320
TI  - Which Factors Influence Self-Efficacy in Patients with Chronic Inflammatory
      Polyarthritis?
AB  - OBJECTIVES: Patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or
      unspecified polyarthritis (UA) deal with several symptoms such as joint
      stiffness, pain, physical limitations and fatigue. Self-efficacy is about
      patients' beliefs and abilities to handle the symptoms and implications of having
      arthritis. Patients' self-efficacy is also a phenomenon that nurses may affect
      through patient education. Therefore, the aim of the present study was to
      investigate the factors that predict self-efficacy in patients with chronic
      inflammatory polyarthritis. METHODS: The participants (n = 132) were recruited
      from St Olavs University Hospital in central Norway from 2008 to 2010, and
      consisted of adult patients with RA, PsA or UA. We performed secondary analyses
      on data collected in a randomized controlled trial studying the long-term effects
      of nurse-led patient education. We carried out bivariate and multivariate linear
      regression analyses. The predictor variables consisted of baseline data on
      demographics, disease characteristics (diagnosis, disease duration, disease
      activity, use of disease-modifying anti-rheumatic drugs, pain and tiredness) and
      psychological variables (well-being, psychological distress and patient
      activation). The dependent variables were self-efficacy over other symptoms and
      self-efficacy over for pain after one year. RESULTS: The analyses showed that
      female gender and patient activation predicted higher self-efficacy over other
      symptoms, whereas female gender and better well-being predicted higher self
      efficacy over pain. CONCLUSION: To strengthen arthritis patients' self-efficacy,
      nurses need to focus on patients' well-being and activation. Nurses also need to
      be aware of possible gender differences regarding patients' self-efficacy.
      Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 26311321
TI  - Making MTM implementable and sustainable in community pharmacy: Is it time for a
      different game plan?
AB  - Although the literature has demonstrated positive patient outcomes from
      medication therapy management (MTM), implementing it in community pharmacy
      continues to be met with significant barriers. To make MTM implementation more
      attainable, scalable, and sustainable in community pharmacies, this paper puts
      out a call for the need to identify the proportion of patients who clinically
      qualify for various levels of intensity of MTM services. This paper presents
      three proposed levels of MTM: adherence management (lowest level of MTM
      intensity), interventions on drug-related problems (mid-level MTM intensity), and
      disease state management (highest level of intensity). It is hypothesized that
      the lowest levels of MTM intensity would be sufficient to address medication
      problems in the vast majority of patients and require fewer MTM skills and
      resources, while the highest levels of MTM intensity (requiring the most skills
      and resources) would address medication problems in the smallest number of
      patients whose medication problems could not resolved with lower-intensity MTM.
      Future research in this area will involve testing previously designed instruments
      to determine why patients are not adhering to their medication regimen, following
      patients who have already had their adherence managed with medication
      synchronization, and tracking patients who will require higher levels of pharmacy
      services. 

PMID- 26311322
TI  - Revisiting the taxonomical classification of Porcine Circovirus type 2 (PCV2):
      still a real challenge.
AB  - BACKGROUND: PCV2 has emerged as one of the most devastating viral infections of
      swine farming, causing a relevant economic impact due to direct losses and
      control strategies expenses. Epidemiological and experimental studies have
      evidenced that genetic diversity is potentially affecting the virulence of PVC2.
      The growing number of PCV2 complete genomes and partial sequences available at
      GenBank questioned the accepted PCV2 classification. METHODS: Nine hundred
      seventy five PCV2 complete genomes and 1,270 ORF2 sequences available from
      GenBank were subjected to recombination, PASC and phylogenetic analyses and
      results were used for comparison with previous classification scheme. RESULTS:
      The outcome of these analyses favors the recognition of four genotypes on the
      basis of ORF2 sequences, namely PCV2a, PCV2b, PCV2c and PCV2d-mPCV2b. To deal
      with the difficulty of founding an unambiguous classification and accounting the
      impossibility to define a p-distance cut-off, a set of reference sequences that
      could be used in further phylogenetic studies for PCV2 genotyping was
      established. Being aware that extensive phylogenetic analyses are time-consuming
      and often impracticable during routine diagnostic activity, ORF2 nucleotide
      positions adequately conserved in the reference sequences were identified and
      reported to allow a quick genotype differentiation. CONCLUSIONS: Globally, the
      present work provides an updated scenario of PCV2 genotypes distribution and,
      based on the limits of the previous classification criteria, proposes new rapid
      and effective schemes for differentiating the four defined PCV2 genotypes.

PMID- 26311323
TI  - Growth kinetics of Cu6Sn5 intermetallic compound at liquid-solid interfaces in
      Cu/Sn/Cu interconnects under temperature gradient.
AB  - The growth behavior of intermetallic compounds (IMCs) at the liquid-solid
      interfaces in Cu/Sn/Cu interconnects during reflow at 250  degrees C and 280 
      degrees C on a hot plate was investigated. Being different from the symmetrical
      growth during isothermal aging, the interfacial IMCs showed clearly asymmetrical
      growth during reflow, i.e., the growth of Cu6Sn5 IMC at the cold end was
      significantly enhanced while that of Cu3Sn IMC was hindered especially at the hot
      end. It was found that the temperature gradient had caused the mass migration of
      Cu atoms from the hot end toward the cold end, resulting in sufficient Cu atomic
      flux for interfacial reaction at the cold end while inadequate Cu atomic flux at
      the hot end. The growth mechanism was considered as reaction/thermomigration
      controlled at the cold end and grain boundary diffusion/thermomigration
      controlled at the hot end. A growth model was established to explain the growth
      kinetics of the Cu6Sn5 IMC at both cold and hot ends. The molar heat of transport
      of Cu atoms in molten Sn was calculated as + 11.12 kJ/mol at 250  degrees C and +
      14.65 kJ/mol at 280  degrees C. The corresponding driving force of
      thermomigration in molten Sn was estimated as 4.82 * 10(-19) N and 6.80 * 10(-19)
      N. 

PMID- 26311324
TI  - The augmentation of O-GlcNAcylation reduces glyoxal-induced cell injury by
      attenuating oxidative stress in human retinal microvascular endothelial cells.
AB  - It has recently been reported that O-linked beta-N-acetyl glucosamine (O-GlcNAc)
      modification (a simple intracellular serine (Ser)/threonine (Thr)-linked
      monosaccharide) in human retinal microvascular endothelial cells (HRECs) is
      related to diabetic retinopathy (DR). During O-GlcNAcylation, O-GlcNAc is added
      to Ser and Thr residues. As the generation of reactive oxygen species (ROS) is
      one of the characteristics of advanced glycation end product (AGE) injury, and
      the most important key pathogenic factor of DR, in the present study, we aimed to
      investigate the association between O-GlcNAcylation and ROS generation in order
      to ascertain whether O-GlcNAcylation mitigates cellular injury through the
      generation of ROS. For this purpose, HRECs were divided into 4 groups as follows:
      HRECs treated with normal glucose (5 mM), HRECs treated with glyoxal (500 uM),
      glyoxal-treated HRECs also treated with 200 uM PUGNAc, and glyoxal-treated HRECs
      infected with O-GlcNAc transferase (OGT) siRNA. We detected increased O-GlcNAc
      levels and increased ROS production in the glyoxal-treated HRECs. The cellular
      redox status was determined by cellular ROS staining and by measuring the
      expression levels of the antioxidant genes, superoxide dismutase (SOD) and
      glutathione peroxidase (GPX). While the augmentation of O-GlcNAcylation following
      treatment with PUGNAc significantly attenuated the production of ROS (p<0.01) and
      increased the expression levels of SOD and GPX, the reduction of O-GlcNAcylation
      following infection with OGT siRNA, exacerbated the production of ROS (p<0.01)
      and decreased the expression of antioxidant genes. The effects of O-GlcNAcylation
      on the viability of HRECs were significant (p<0.01), particularly in the hydrogen
      peroxide (H2O2)-treated HRECs. Treatment with PUGNAc reduced glyoxal-induced cell
      apoptosis and transfection with OGT siRNA increased HREC apoptosis; these results
      were confirmed by flow cytometry and by the assessment of mitochondrial membrane
      potential. The augmentation of O-GlcNAcylation exerted cytoprotective effects on
      the HRECs by reducing the generation of ROS, increasing the expression of
      antioxidant genes, preventing the dissipation of mitochondrial membrane potential
      and preventing HREC apoptosis. Therefore, it can be concluded that O
      GlcNAcylation plays a role in the early developmental process of DR. 

PMID- 26311325
TI  - Improving medication adherence in stroke patients through Short Text Messages
      (SMS4Stroke)-study protocol for a randomized, controlled trial.
AB  - BACKGROUND: Stroke is a major cause of morbidity and mortality, especially in low
      and middle income countries. Medical management is the mainstay of therapy to
      prevent recurrence of stroke. Current estimates are that only 1 in 6 patients
      have perfect adherence to medication schedules. Using SMS (Short Messaging
      Service) as reminders to take medicines have been used previously for diseases
      such as diabetes and HIV with moderate success. We aim to explore the
      effectiveness and acceptability of SMS in increasing adherence to medications in
      patients with stroke. METHODS: This will be a randomized, controlled, assessor
      blinded single center superiority trial. Adult participants with access to a cell
      phone and a history of stroke longer than 1 month on multiple risk modifying
      medications will be selected from Neurology and Stroke Clinic. They will be
      randomized into two parallel groups in a 1:1 ratio via block technique with one
      group receiving the standard of care as per institutional guidelines while the
      parallel group receiving SMS reminders for each dose of medicine in addition to
      the standard of care. In addition intervention group will receive messages for
      lifestyle changes, medication information, risk factors and motivation for
      medication adherence. These will bemodeled on Social Cognitive Theory and Health
      Belief Model and will be categorized by Michies Taxonomy of Behavioral Change
      Communication. Patient compliance to medicines will be measured at baseline and
      then after 2 months in each group by using the Morisky Medication Adherence
      Scale. The change in compliance to medication regimen after the intervention and
      the difference between the two groups will be used to determine the effectiveness
      of SMS reminders as a tool to increase medication compliance. The acceptability
      of the SMS will be determined by a tool designed for this study whose attributes
      are based Rogers Diffusion of innovation theory. A sample size of 86 participants
      in each arm will be sufficient to detect a difference of 1 point on the MMAS with
      a power of 90 % and significance level of 5 % between the two groups; using an
      attrition rate of 15 %, 200 participants in all will be randomized. DISCUSSION:
      The SMS for Stroke Study will provide evidence for feasibility and effectiveness
      of SMS in improving post stroke medication adherence in an LMIC setting. TRIAL
      REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT01986023 11 /11/2013.

PMID- 26311327
TI  - What is good publication practice, what is ISMPP, and why you should care.

PMID- 26311326
TI  - The effects of human Wharton's jelly cell transplantation on the intervertebral
      disc in a canine disc degeneration model.
AB  - INTRODUCTION: Cell-based therapy was a promising treatment method for disc
      degenerative diseases. Wharton's jelly cell (WJC) has been explored to cure
      various human diseases, while it still remains unknown about this MSC for disc
      repair. In our prior work, WJCs could differentiate into nucleus pulposus (NP)
      like cells by co-culturing with NP cells in vitro. Thence, the aim of this study
      was further to investigate the survival and function of WJCs in vivo after
      transplantation into degenerated canine discs. METHOD: WJCs were isolated from
      human umbilical cords and labeled with EGFP. The degeneration of L4-5, L5-6, and
      L6-7 discs of beagles was induced by aspirating the NP tissues. Four weeks after
      the operation, the injured discs were left to be no treatment at L4-5 (DS group),
      injected with 0.9 % saline at L5-6 (FS group), and transplanted with EGFP-labeled
      WJCs at L6-7 (TS group). In all animals, the intact disc L3-4 served as a control
      (CS group). The animals were followed up for 24 weeks after initial operation.
      Spine imaging was evaluated at 4, 8, 12, and 24 weeks, respectively. Histologic,
      biomechanics and gene expression analyses were performed at 24 weeks.
      Immunohistochemistry for aggrecan, types II collagen, SOX-9 was employed to
      investigate the matrix formation in the NP. RESULTS: The TS group showed a
      significantly smaller reduction in the disc height and T2-weighted signal
      intensity, and a better spinal segmental stability than DS and FS groups.
      Histologic assay demonstrated that WJCs were specifically detected in TS group at
      24 weeks and the discs of TS group maintained a relatively well preserved
      structure as compared to the discs of DS and FS groups. Furthermore, real-time
      PCR and immunohistochemistry demonstrated that expressions of disc matrix genes,
      aggrecan, type II collagen, and SOX-9, were up-regulated in TS group compared to
      DS and FS groups. CONCLUSION: WJCs could not only survive in the degenerate IVDs,
      but also promote the disc matrix formation of aggrecan and type II collagen in
      the degenerate IVDs. It may have value in cell-based therapy for degenerative
      disc disease.

PMID- 26311328
TI  - Publication planning: promoting an ethics of transparency and integrity in
      biomedical research.
AB  - Biomedical research should include plans to communicate complete and accurate
      results to the scientific community and the public in a timely manner. All too
      often, however, such planning is lacking until after data have been generated. We
      developed a collaborative professional statement following review of the indexed
      biomedical literature and relevant professional society guidelines. Planning for
      publications before, during and after biomedical research studies are conducted
      promotes the timely dissemination of accurate and comprehensive results.
      Effective publication planning accounts for the work of all contributors,
      encourages full transparency and contributes to overall scientific integrity.
      Although the most obvious contribution of publication planning is to result
      dissemination, the best planning may also help improve the overall quality of
      research study design and the overall integrity of study conduct by keeping the
      final audience in the forefront of the investigators' attention. Publication
      planning can help biomedical researchers achieve and maintain high standards of
      transparency and integrity. Table 1 below highlights briefly some of the aspects
      to be included in a publication plan.

PMID- 26311329
TI  - Lower limb lymphatic flow and venous leg ulcers formation and healing.

PMID- 26311330
TI  - Risk factors for delayed healing in venous leg ulcers: a review of the
      literature.

PMID- 26311331
TI  - [Peri-interventional management of acute endovascular stroke treatment].
AB  - Due to the ground breaking consistent evidence that supports the effect of
      endovascular stroke treatment (EST), many acute care hospitals and stroke centers
      will have to be prepared to provide this treatment in an optimal way within the
      coming years. In addition to the intervention itself, patient preparation,
      stabilization and monitoring during the treatment as well as the aftercare
      represent significant challenges and have mostly not yet been sufficiently
      investigated. Under these aspects, the questions of optimal sedation and airway
      management have received the highest attention. Based on retrospective study
      results it already seems to be justified, respecting certain criteria, to prefer
      EST with the patient under conscious sedation (CS) in comparison to general
      anesthesia (GA) and to only switch to GA in cases of emergency until this
      question has been clarified by prospective studies. This and other aspects of
      peri-interventional management, such as logistics, monitoring, blood pressure,
      ventilation settings, postprocedural steps of intensive or stroke unit care and
      imaging follow-up are summarized in this overview. The clinical and radiological
      selection of patients and thus the decision for intervention or technical aspects
      of the intervention itself will not be part of this article. 

PMID- 26311332
TI  - [Atrial appendage occlusion in atrial fibrillation? Con].

PMID- 26311333
TI  - Differences of oral health conditions between adults and older adults: A census
      in a Southern Brazilian city.
AB  - AIM: To assess differences in the oral diseases/conditions between adults and
      older adults. METHODS: A cross-sectional study was carried out with all adults
      and older adults in Luzerna, South Brazil (n = 569). Clinical data included use
      of and need for dental prostheses; number of decayed, missing and filled teeth;
      and temporomandibular disorder. Differences between adults and older adults were
      evaluated using chi(2) -tests. Associations between independent variables and the
      use of and need for dental prostheses were determined using Poisson regression
      analyses (P < 0.05). RESULTS: Increased number of decayed, missing and filled
      teeth, use of and need for dental prostheses, higher use of complete dentures,
      and fewer temporomandibular disorder signs and symptoms were observed in older
      adults. After adjustments, lower social class (P = 0.001) and unmarried status (P
      = 0.05) were associated with greater need for prosthetic rehabilitation. Women (P
      = 0.02), older individuals (P < 0.001) and those of lower socioeconomic status (P
      = 0.001) had a higher risk of using prostheses. CONCLUSION: A significant
      difference of oral conditions between adults and older adults was observed. The
      frequency of use of and need for dental prostheses was higher for older adults,
      although they had reported lower frequency of temporomandibular disorder. Women,
      married and individuals of higher socioeconomic status showed better oral health
      conditions. Geriatr Gerontol Int 2016; 16: 1014-1020.

PMID- 26311334
TI  - Adhesion of MRC-5 and A549 cells on poly(dimethylsiloxane) surface modified by
      proteins.
AB  - PDMS is a very popular material used for fabrication of Lab-on-a-Chip systems for
      biological applications. Although PDMS has numerous advantages, it is a highly
      hydrophobic material, which inhibits adhesion and proliferation of the cells.
      PDMS surface modifications are used to enrich growth of the cells. However, due
      to the fact that each cell type has specific adhesion, it is necessary to
      optimize the parameters of these modifications. In this paper, we present an
      investigation of normal (MRC-5) and carcinoma (A549) human lung cell adhesion and
      proliferation on modified PDMS surfaces. We have chosen these cell types because
      often they are used as models for basic cancer research. To the best of our
      knowledge, this is the first presentation of this type of investigation. The
      combination of a gas-phase processing (oxygen plasma or ultraviolet irradiation)
      and wet chemical methods based on proteins' adsorption was used in our
      experiments. Different proteins such as poly-l-lysine, fibronectin, laminin,
      gelatin, and collagen were incubated with the activated PDMS samples. To compare
      with other works, here, we also examined how ratio of prepolymer to curing agent
      (5:1, 10:1, and 20:1) influences PDMS hydrophilicity during further
      modifications. The highest adhesion of the tested cells was observed for the
      usage of collagen, regardless of PDMS ratio. However, the MRC-5 cell line
      demonstrated better adhesion than A549 cells. This is probably due to the
      difference in their morphology and type (normal/cancer). 

PMID- 26311335
TI  - Paper-Based Electrochemical Cell Coupled to Mass Spectrometry.
AB  - On-line coupling of electrochemistry (EC) to mass spectrometry (MS) is a powerful
      approach for identifying intermediates and products of EC reactions in situ. In
      addition, EC transformations have been used to increase ionization efficiency and
      derivatize analytes prior to MS, improving sensitivity and chemical specificity.
      Recently, there has been significant interest in developing paper-based
      electroanalytical devices as they offer convenience, low cost, versatility, and
      simplicity. This report describes the development of tubular and planar paper
      based electrochemical cells (P-EC) coupled to sonic spray ionization (SSI) mass
      spectrometry (P-EC/SSI-MS). The EC cells are composed of paper sandwiched between
      two mesh stainless steel electrodes. Analytes and reagents can be added directly
      to the paper substrate along with electrolyte, or delivered via the SSI
      microdroplet spray. The EC cells are decoupled from the SSI source, allowing
      independent control of electrical and chemical parameters. We utilized P-EC/SSI
      MS to characterize various EC reactions such as oxidations of cysteine, dopamine,
      polycyclic aromatic hydrocarbons, and diphenyl sulfide. Our results show that P
      EC/SSI-MS has the ability to increase ionization efficiency, to perform online EC
      transformations, and to capture intermediates of EC reactions with a response
      time on the order of hundreds of milliseconds. The short response time allowed
      detection of a deprotonated diphenyl sulfide intermediate, which experimentally
      confirms a previously proposed mechanism for EC oxidation of diphenyl sulfide to
      pseudodimer sulfonium ion. This report introduces paper-based EC/MS via
      development of two device configurations (tubular and planar electrodes), as well
      as discusses the capabilities, performance, and limitations of the technique.

PMID- 26311336
TI  - Weight-based discrimination: an ubiquitary phenomenon?
AB  - BACKGROUND: Despite strong indications of a high prevalence of weight-related
      stigmatization in individuals with obesity, limited attention has been given to
      the role of weight discrimination in examining the stigma obesity. Studies, up to
      date, rely on a limited basis of data sets and additional studies are needed to
      confirm the findings of previous studies. In particular, data for Europe are
      lacking, and are needed in light of a recent ruling of the European Court of
      Justice that addressed weight-based discrimination. METHODS: The data were
      derived from a large representative telephone survey in Germany (n=3003). The
      dependent variable, weight-based discrimination, was assessed with a one-item
      question. The lifetime prevalence of weight discrimination across different
      sociodemographic variables was determined. Logistic regression models were used
      to assess the association of independent and dependent variables. A sub-group
      analysis was conducted analyzing all participants with a body mass index ?25 kg
      m(-)(2). RESULTS: The overall prevalence of weight-based discrimination was 7.3%.
      Large differences, however, were observed regarding weight status. In normal
      weight and overweight participants the prevalence was 5.6%, but this number
      doubled in participants with obesity class I (10.2%), and quadrupled in
      participants with obesity class II (18.7%) and underweight (19.7%). In
      participants with obesity class III, every third participant reported accounts of
      weight-based discrimination (38%). In regression models, after adjustment, the
      associations of weight status and female gender (odds ratio: 2.59, P<0.001)
      remained highly significant. CONCLUSIONS: Discrimination seems to be an
      ubiquitary phenomenon at least for some groups that are at special risk, such as
      heavier individuals and women. Our findings therefore emphasize the need for
      research and intervention on weight discrimination among adults with obesity,
      including anti-discrimination legislation.

PMID- 26311338
TI  - Lessons learned in Andrology: revelations on a road less traveled.

PMID- 26311339
TI  - Mycoplasma and ureaplasma infection and male infertility: a systematic review and
      meta-analysis.
AB  - The relationship between mycoplasma and ureaplasma infection and male infertility
      has been studied widely; however, results remain controversial. This meta
      analysis investigated the association between genital ureaplasmas (Ureaplasma
      urealyticum, Ureaplasma parvum) and mycoplasmas (Mycoplasma hominis, Mycoplasma
      genitalium), and risk of male infertility. Differences in prevalence of
      ureaplasma and mycoplasma infection between China and the rest of the world were
      also compared. Study data were collected from PubMed, Embase and the China
      National Knowledge Infrastructure. Summary odds ratio (OR) with 95% confidence
      interval (CI) was applied to assess the relationship. Heterogeneity testing and
      publication bias testing were also performed. A total of 14 studies were used:
      five case-control studies with 611 infertile cases and 506 controls featuring U.
      urealyticum infection, and nine case-control studies with 2410 cases and 1223
      controls concerning M. hominis infection. Two other infection (U. parvum and M.
      genitalium) were featured in five and three studies, respectively. The meta
      analysis results indicated that U. parvum and M. genitalium are not associated
      with male infertility. However, a significant relationship existed between U.
      urealyticum and M. hominis and male infertility. Comparing the global average
      with China, a significantly higher positive rate of U. urealyticum, but a
      significantly lower positive rate of M. hominis, was observed in both the
      infertile and control groups in China. 

PMID- 26311337
TI  - MicroRNAs as regulators of metabolic disease: pathophysiologic significance and
      emerging role as biomarkers and therapeutics.
AB  - The prevalence of overweight and obesity in developed and developing countries
      has greatly increased the risk of insulin resistance and type 2 diabetes
      mellitus. It is evident from human and animal studies that obesity alters
      microRNA (miRNA) expression in metabolically important organs, and that miRNAs
      are involved in changes to normal physiology, acting as mediators of disease.
      miRNAs regulate multiple pathways including insulin signaling, immune-mediated
      inflammation, adipokine expression, adipogenesis, lipid metabolism, and food
      intake regulation. Thus, miRNA-based therapeutics represent an innovative and
      attractive treatment modality, with non-human primate studies showing great
      promise. In addition, miRNA measures in plasma or bodily fluids may be used as
      disease biomarkers and predictors of metabolic disease in humans. This review
      analyzes the role of miRNAs in obesity and insulin resistance, focusing on the
      miR-17/92, miR-143-145, miR-130, let-7, miR-221/222, miR-200, miR-223, miR-29 and
      miR-375 families, as well as miRNA changes by relevant tissue (adipose, liver and
      skeletal muscle). Further, the current and future applications of miRNA-based
      therapeutics and diagnostics in metabolic disease are discussed. 

PMID- 26311340
TI  - An integrated approach with vardenafil orodispersible tablet and cognitive
      behavioral sex therapy for treatment of erectile dysfunction: a randomized
      controlled pilot study.
AB  - Erectile Dysfunction is considered a multifactorial disease, where organic and
      psychological aspects are often interconnected. In a randomized controlled pilot
      study, we compared the efficacy of combined vardenafil orodispersible tablet
      (VARD) and cognitive-behavioral sex therapy (CBST) vs. VARD alone in improving
      sexual symptoms in both male and female partners. Thirty male patients with
      erectile dysfunction, and their partners were randomly assigned with a 2 : 1
      ratio, to two different arms and treated for 10 weeks with VARD (Group A; n = 19)
      or VARD+CBST (Group B; n = 11). International Index of Erectile Dysfunction (IIEF
      15), Female Sexual Function Index (FSFI) and Index of Sexual Satisfaction (ISS)
      were, respectively, administered to male, female, and both partners at times (T)
      0, 1 (+5 weeks of therapy) and 2 (+10 weeks of therapy). Groups A and B were
      similar in their sociodemographic and clinical characteristics. Pre-treatment
      (T0) test scores did not significantly differ among the groups. In both group A
      and B, the IIEF-Erectile Function domain showed a significant improvement from T0
      to T1 (p = 0.005 and p < 0.0001 vs. T0, respectively) and from T0 to T2 only in
      group B (p = 0.013). In group A, FSFI and both male and female ISS did not show
      any significant change at T1 and T2 vs. T0. In group B, a significant improvement
      at final time-point in FSFI and male and female ISS scores was reported (p <
      0.05, T2 vs. T0 in all scores). The results of our study suggest that both VARD
      alone and VARD+CBST improved erectile function, however, only VARD+CBST improved
      couple sexual satisfaction and female sexual function. 

PMID- 26311341
TI  - Restoration of erectile function with intracavernous injections of endothelial
      progenitor cells after bilateral cavernous nerve injury in rats.
AB  - Endothelial progenitor cells (EPCs) are bone marrow-derived endothelial cells
      capable of circulating, proliferating, and differentiating into mature
      endothelial cells. Circulating EPCs can be directly recruited to some extent at
      sites of injury, and their administration could accelerate repair or
      endothelialization of the damaged tissue. We investigated the effects of
      intracavernous injections of EPCs into the corpora cavernosa of rats with
      erectile dysfunction (ED) caused by bilateral cavernous nerve (CN) injury.
      Overall, 24 male Sprague-Dawley rats were randomized into three groups: sham
      surgery, vehicle-only, or EPC treatment. Rats in the EPC treatment and vehicle
      only groups were subjected to bilateral CN injury before injection of EPCs or
      vehicle, respectively, into the corpora cavernosa. Four weeks after surgery,
      erectile function was assessed by measuring maximum intracavernosal pressure
      (ICP), change in ICP, area under the ICP curve, and ratio of change in ICP and
      mean arterial pressure (MAP; DeltaICP/MAP). Penile tissue was
      histomorphometrically analyzed for the expression of neural nitric oxide synthase
      (nNOS), neurofilament-1 (NF-1), von Willebrand factor (vWF), endothelial NOS
      (eNOS), and smooth muscle cell content. Maximum ICP and all other functional
      parameters of erectile function were significantly reduced in the vehicle-only
      group vs. the sham and EPC treatment groups (all p < 0.001). Smooth muscle cell
      content was decreased in the vehicle-only vs. the sham and EPC treatment groups
      (both p < 0.01). Expressions of vWF and eNOS in the dorsal artery were
      significantly higher in the EPC treatment than the vehicle-only group (p < 0.05).
      In conclusion, EPC treatment restored erectile function in a rat model of
      bilateral CN injury through recruitment of EPCs toward the dorsal artery and
      preservation of smooth muscle cells in the corpus cavernosum. These findings
      elucidate the therapeutic potential of EPCs for treating ED in humans. 

PMID- 26311342
TI  - Nicotine elevates sperm motility and induces Pfn1 promoter hypomethylation in
      mouse testis.
AB  - Many studies have addressed the hazardous role of cigarette smoking on male
      fertility, but the exact molecular mechanisms involved in the impairments caused
      by nicotine remain unclear. To evaluate the detrimental effects of nicotine
      exposure on spermatogenesis, two-dimensional gel electrophoresis and mass
      spectrometry analysis were performed to screen and identify differentially
      expressed proteins from the testes of mice exposed to nicotine daily. Data mining
      analysis indicated that the 15 identified proteins were mainly involved in actin
      cytoskeleton regulation and in the tricarboxylic acid cycle, which are related to
      cell motility. Further investigation of a central regulatory factor in the
      cytoskeleton regulation, profilin 1 (PFN1), revealed that nicotine-induced Pfn1
      over-expression in mouse testes, specifically in elongated spermatids, by Pfn1
      promoter hypomethylation. Interestingly, elevated sperm motility parameters were
      observed in nicotine-treated mice. We assume that nicotine-induced PFN1 over
      expression in mouse spermatids may promote actin polymerization and ultimately
      enhance sperm motility. 

PMID- 26311343
TI  - Rapamycin (Sirolimus) alters mechanistic target of rapamycin pathway regulation
      and microRNA expression in mouse meiotic spermatocytes.
AB  - Mechanistic target of rapamycin (mTOR) is a signal transduction pathway that
      modulates translation initiation in several animals including mammals.
      Rapamaycin, an allosteric inhibitor of mTOR pathway, is often used as an
      immunosuppressive drug following kidney transplantation and causes gonadal
      dysfunction and defects in spermatogenesis. The molecular mechanism behind
      rapamycin-mediated testicular dysfunction is not known. We have therefore
      explored the contribution of rapamycin in mTOR regulation and microRNA (miRNA)
      expression in mouse spermatocytes, the intermediate stage of spermatogenesis,
      where meiosis takes place. In the present study, we optimized the isolation of
      highly pure and viable spermatocytes by flow sorting, treated them with
      rapamycin, and investigated the expression of mTOR and downstream effector
      molecules. Western blot and immunocytochemical analysis confirm that rapamycin
      treatment suppresses mTOR and phopsphorylated P70S6 kinase activities in
      spermatocytes, but not that of phosphorylated 4E-binding protein 1. Also,
      rapamycin treatment modulates the expression of several spermatocyte-specific
      miRNAs. To complement these finding an in vivo study was also performed. In
      silico prediction of target genes of these miRNAs and their functional pathway
      analysis revealed that, several of them are involved in crucial biological
      process, cellular process and catalytic activities. miRNA-transcription factor
      (TF) network analysis enlisted different TFs propelling the transcription
      machineries of these miRNAs. In silico prediction followed by quatitative real
      time PCR revealed two of these TFs namely, PU.1 and CCCTC binding factor (CTCF)
      are down and upregulated, respectively, which may be the reason of the altered
      expression of miRNAs following rapamycin treatment. In conclusion, for the first
      time, the present study provides insight into how rapamycin regulates mTOR
      pathway and spermatocyte-specific miRNA expression which in turn, regulate
      expression of target genes post-transcriptionally. 

PMID- 26311344
TI  - Genetic factors derived from the MRL/MpJ mouse function to maintain the integrity
      of spermatogenesis after heat exposure.
AB  - MRL/MpJ mice possess highly heat-shock-resistant spermatocytes (HRS) in
      comparison with C57BL/6 mice. This resistance depends on the MRL/MpJ-type loci at
      the 81 cM region of Chromosome (Chr) 1 and the 40 cM region of Chr 11. To
      evaluate the functions of these loci in detail, we examined the histopathological
      changes resulting from experimental cryptorchidism or transient scrotal heat
      stress (SHS) in the testes of C57BL/6-based congenic strains (B6.MRLc1,
      B6.MRLc11, and B6.MRLc1c11) carrying the MRL/MpJ-derived loci responsible for
      HRS. Among cryptorchid testes from congenic strains, those in B6.MRLc1c11 mice
      showed the highest heat resistance, indicating that the genetic interactions
      between MRL/MpJ-derived HRS loci on Chrs 1 and 11 may be important for
      maintaining spermatogenesis under continuous testicular hyperthermia. In
      contrast, immediately after SHS induction, germ cell loss via apoptosis was
      inhibited in B6.MRLc11 and B6.MRLc1c11 mice, similar to that in MRL/MpJ mice.
      However, this HRS phenotype was not observed in C57BL/6 or B6.MRLc1 mice after
      SHS induction. Furthermore, testicular calcification owing to long-term damage by
      SHS induction was inhibited in all congenic strains in comparison with that in
      C57BL/6 mice, indicating that each MRL/MpJ-derived locus on Chrs 1 and 11 acted
      independently to facilitate the recovery of heat-induced testicular damage by
      inhibiting calcification. B6.MRLc11 and B6.MRLc1c11 mice showed greater recovery
      in spermatogenesis than B6.MRLc1 mice 60 days after SHS induction. Therefore, the
      MRL/MpJ-derived HRS locus on Chr 11 might play an important role in recovery from
      heat stress damage. On the basis of these results, we concluded that MRL/MpJ
      derived loci on Chrs 1 and 11 cooperatively or independently regulate testicular
      heat sensitivity depending on the various heat stresses. 

PMID- 26311345
TI  - E2F1 controls germ cell apoptosis during the first wave of spermatogenesis.
AB  - Cell cycle control during spermatogenesis is a highly complex process owing to
      the control of the mitotic expansion of the spermatogonial cell population and
      following meiosis, induction of DNA breaks during meiosis and the high levels of
      physiological germ-cell apoptosis. We set out to study how E2F1, a key controller
      of cell cycle, apoptosis, and DNA damage responses, functions in the developing
      and adult testis. We first analyzed the expression pattern of E2f1 during post
      natal testis development using RNA in situ hybridization, which showed a
      differential expression pattern of E2f1 in the adult and juvenile mouse testes.
      To study the function of E2f1, we took advantage of the E2F1(-/-) mouse line,
      which was back-crossed to C57Bl/6J genetic background. E2f1 loss led to a severe
      progressive testicular atrophy beginning at the age of 20 days. Spermatogonial
      apoptosis during the first wave of spermatogenesis was decreased. However,
      already in the first wave of spermatogenesis an extensive apoptosis of
      spermatocytes was observed. In the adult E2F1(-/-) testes, the atrophy due to
      loss of spermatocytes was further exacerbated by loss of spermatogonial stem
      cells. Surprisingly, only subtle changes in global gene expression array
      profiling were observed in E2F1(-/-) testis at PND20. To dissect the changes in
      each testicular cell type, an additional comparative analysis of the array data
      was performed making use of previously published data on transcriptomes of the
      individual testicular cell types. Taken together, our data indicate that E2F1 has
      a differential role during first wave of spermatogenesis and in the adult testis,
      which emphasizes the complex nature of cell cycle control in the developing
      testis. 

PMID- 26311346
TI  - Pseudoclavibacter terrae sp. nov. isolated from rhizosphere soil of Ophiopogon
      japonicus.
AB  - Strain THG-MD12T, a Gram-reaction-positive, aerobic, non-motile, rod-shaped
      bacterium was isolated from rhizosphere soil of Ophiopogon japonicus in PR China.
      THG-MD12T was closely related to members of the genus Pseudoclavibacter and
      showed the highest 16S rRNA gene sequence similarities with Pseudoclavibacter
      helvolus KCTC 19531T (98.8 %) and Pseudoclavibacter chungangensis KCTC 22691T
      (96.9 %). DNA-DNA hybridization showed 41.9 +/- 2.1 % and 12.4 +/- 0.9 % DNA
      reassociation with P. helvolus KCTC 19531T and P. chungangensis KCTC 22691T,
      respectively. Chemotaxonomic analyses revealed that strain THG-MD12T possesses
      menaquinone-9 as the predominant respiratory quinone, 2,4-diaminobutyric acid as
      the diamino acid in the peptidoglycan and anteiso-C15 : 0, iso-C16 : 0, C16 : 0
      and anteiso-C17 : 0 as the major fatty acids. The polar lipid profile was found
      to consist of diphosphatidylglycerol, phosphatidylglycerol, two unknown
      glycolipids and two unknown lipids. These data corroborated the affiliation of
      THG-MD12T to the genus Pseudoclavibacter. Thus, the isolate represents a novel
      species, for which the name Pseudoclavibacter terrae sp. nov. is proposed, with
      THG-MD12T as the type strain ( = CCTCC AB 2015124T = KCTC 39562T).

PMID- 26311347
TI  - Cardiovascular response to short-term fasting in menstrual phases in young women:
      an observational study.
AB  - BACKGROUND: Menstrual cycle-related symptoms are an important health issue for
      many women, and some may affect cardiac autonomic regulation. In the present
      study, we evaluated the cardiovascular and physiological stress response to 12-h
      short-term fasting in the menstrual phases of healthy young women. METHODS: We
      performed a randomized crossover study. Subjects were seven female university
      students (age: 22.3 +/- 1.0 years). The experiments comprised four sessions: meal
      intake in the follicular phase, meal intake in the luteal phase, fasting in the
      follicular phase, and fasting in the luteal phase. All subjects participated in a
      total of four experimental sessions during two successive phases (follicular and
      luteal phase in the same menstrual cycle, or luteal phase and follicular phase in
      the next menstrual cycle) according to a randomized crossover design. R-R
      intervals were continuously recorded before and after meals, and power spectral
      analysis of heart rate variability was performed. Other physiological data were
      obtained before and 20, 40, 60, and 80 min after meal intake or after the
      corresponding time point of meal intake (fasting in the follicular or luteal
      phase). RESULTS: Heart rate decreased during fasting in the follicular and luteal
      phases. High frequency power increased during fasting in the follicular and
      luteal phases. In addition, salivary cortisol concentrations decreased during
      fasting in the luteal phase. CONCLUSIONS: In the present study, short-term
      fasting resulted in higher parasympathetic activity and lower cortisol levels in
      the luteal phase in these young women. These results indicate a possibility to
      produce an anti-stress effect in the luteal phase, which may reduce menstrual
      symptoms.

PMID- 26311348
TI  - Prospectively-followed pregnancies in patients with inflammatory arthritis taking
      biological drugs: an Italian multicentre study.
AB  - OBJECTIVES: Information on new drugs does not include their possible effects on
      pregnancy because pregnant women are excluded from clinical trials. Although not
      classified as teratogenic in animals, limited data is available on biological
      anti-rheumatic agents and their safety in human pregnancy. The aim of the study
      is to evaluate the safety of biological drugs in pregnant patients with chronic
      arthritis. METHODS: Pregnancy outcome and maternal disease variations were
      prospectively followed in six Italian Rheumatology Centres. Patients exposed to
      biological agents during the periconceptional period or during pregnancy were
      included in the study. The occurrence of congenital malformations as well as the
      obstetric and neonatal outcomes were assessed. RESULTS: Between 1999 and 2013 we
      identified 79 exposed pregnancies in 67 women affected by different rheumatic
      diseases with peripheral chronic arthritis. At the time of the start of
      pregnancy, 56 patients were taking etanercept, 13 adalimumab, 3 infliximab, 2
      each certolizumab-pegol and rituximab, 1 each golimumab, anakinra and abatacept.
      Biological treatment was stopped after a mean of 41 days since documented
      pregnancy. Live births were reported in 66% of pregnancies. The rate of
      spontaneous pregnancy loss was 20%. Only one congenital malformation was
      reported. CONCLUSIONS: TNF-alpha inhibitors can be considered safe in the
      periconception period, representing a possible therapeutic choice also in young
      women affected by an aggressive form of chronic arthritis and hoping for a
      pregnancy. Reports of exposure during 2nd/3rd trimester are still limited and
      suggest caution. Experience with abatacept, tocilizumab, anakinra and rituximab
      in pregnancy is insufficient.

PMID- 26311349
TI  - Impact assessment of agricultural driven stressors on benthic macroinvertebrates
      using simulated data.
AB  - Agricultural land use poses a significant threat to the ecological integrity of
      rivers in Europe. Particularly in the Mediterranean, water abstraction and
      nutrient application are anthropogenic pressures that have a significant impact
      on aquatic habitats and biodiversity. In this article, we assessed the effects of
      agricultural management practices on benthic macroinvertebrates in a large river
      basin of central Greece using simulated data based on the application of SWAT
      (Soil Water Assessment Tool) model. Physicochemical and hydrological output
      variables of the model were used as predictors of the ASPT (Average Score Per
      Taxon) metric based on a correlated component regression analysis (CCR) built on
      empirical data. The estimation of ASPT was performed for the wet and dry seasons
      within a 20-year period for a total of 47 subbasins under the baseline conditions
      and after implementing three management scenarios that reduced: a) irrigation
      water applied to crops by 30%, b) chemical fertilization applied to crops by 30%
      and c) both irrigation and fertilization by 30%. The results revealed that
      application of the reduced irrigation resulted to a slight increase of the
      simulated dissolved inorganic nitrogen concentration (DIN), which in turn
      decreased the mean ASPT in 21 of the 47 subbasins implying a negative effect on
      the macroinvertebrate communities. On the contrary, the reduction of
      fertilization as well as the combined scenario decreased both the simulated DIN
      and phosphate concentration causing an increase of the mean ASPT for a total of
      40 of the 47 subbasins. Based on these results, we suggest that the best
      management option is a combined practice of deficit irrigation and fertilization
      reduction since it improved water quality, increased ASPT values and saved a
      considerable amount of water. Overall, this work demonstrates a simple
      methodology that can efficiently assess the effects of agricultural management
      practices on biotic indicators. 

PMID- 26311352
TI  - Modulation of a Molecular pi-Electron System in a Purely Organic Conductor that
      Shows Hydrogen-Bond-Dynamics-Based Switching of Conductivity and Magnetism.
AB  - New important aspects of the hydrogen-bond (H-bond)-dynamics-based switching of
      electrical conductivity and magnetism in an H-bonded, purely organic conductor
      crystal have been discovered by modulating its tetrathiafulvalene (TTF)-based
      molecular pi-electron system by means of partial sulfur/selenium substitution.
      The prepared selenium analogue also showed a similar type of phase transition,
      induced by H-bonded deuterium transfer followed by electron transfer between the
      H-bonded TTF skeletons, and the resulting switching of the physical properties;
      however, subtle but critical differences due to sulfur/selenium substitution were
      detected in the electronic structure, phase transition nature, and switching
      function. A molecular-level discussion based on the crystal structures shows that
      this chemical modification of the TTF skeleton influences not only its own pi
      electronic structure and pi-pi interactions within the conducting layer, but also
      the H-bond dynamics between the TTF pi skeletons in the neighboring layers, which
      enables modulation of the interplay between the H-bond and pi electrons to cause
      such differences. 

PMID- 26311350
TI  - Skipper genome sheds light on unique phenotypic traits and phylogeny.
AB  - BACKGROUND: Butterflies and moths are emerging as model organisms in genetics and
      evolutionary studies. The family Hesperiidae (skippers) was traditionally viewed
      as a sister to other butterflies based on its moth-like morphology and darting
      flight habits with fast wing beats. However, DNA studies suggest that the family
      Papilionidae (swallowtails) may be the sister to other butterflies including
      skippers. The moth-like features and the controversial position of skippers in
      Lepidoptera phylogeny make them valuable targets for comparative genomics.
      RESULTS: We obtained the 310 Mb draft genome of the Clouded Skipper (Lerema
      accius) from a wild-caught specimen using a cost-effective strategy that
      overcomes the high (1.6 %) heterozygosity problem. Comparative analysis of Lerema
      accius and the highly heterozygous genome of Papilio glaucus revealed differences
      in patterns of SNP distribution, but similarities in functions of genes that are
      enriched in non-synonymous SNPs. Comparison of Lepidoptera genomes revealed
      possible molecular bases for unique traits of skippers: a duplication of electron
      transport chain components could result in efficient energy supply for their
      rapid flight; a diversified family of predicted cellulases might allow them to
      feed on cellulose-enriched grasses; an expansion of pheromone-binding proteins
      and enzymes for pheromone synthesis implies a more efficient mate-recognition
      system, which compensates for the lack of clear visual cues due to the
      similarities in wing colors and patterns of many species of skippers.
      Phylogenetic analysis of several Lepidoptera genomes suggested that the position
      of Hesperiidae remains uncertain as the tree topology varied depending on the
      evolutionary model. CONCLUSION: Completion of the first genome from the family
      Hesperiidae allowed comparative analyses with other Lepidoptera that revealed
      potential genetic bases for the unique phenotypic traits of skippers. This work
      lays the foundation for future experimental studies of skippers and provides a
      rich dataset for comparative genomics and phylogenetic studies of Lepidoptera.

PMID- 26311351
TI  - Ya-fish (Schizothorax prenanti) spexin: identification, tissue distribution and
      mRNA expression responses to periprandial and fasting.
AB  - Spexin (SPX) is a novel peptide which was known for its role in physiological
      homeostasis. A recent study has confirmed that SPX plays an important role in the
      feeding regulation. However, the reports about SPX are very limited. In the
      present study, we characterized the structure, distribution and mRNA expression
      responses to feeding status of SPX in Ya-fish (Schizothorax prenanti). The full
      length cDNA of Ya-fish SPX was 1330 base pairs (bp), which encoded 106 amino acid
      residues. These residues contained a 31-amino acid signal peptide region and a 14
      amino acid mature peptide. The sequence alignment demonstrated that the Ya-fish
      SPX showed high conservation with other species. Our data revealed that SPX was
      widely expressed in all test tissues. The highest expression of SPX mRNA was
      observed in Ya-fish forebrain. Compared with the Ya-fish SPX mRNA expression in
      the forebrain between the preprandial and postprandial groups, the fed group was
      prominently increased than unfed groups after a meal, while the unfed group at 1
      and 3 h substantially decreased than preprandial groups (P < 0.01). In addition,
      SPX mRNA expression in forebrain was significantly decreased (P < 0.01) during
      fasting for a week and sharply increased (P < 0.01) after refeeding on the 7th
      day, and then return to normal level on the 9th day. These results point toward
      that SPX mRNA expression is regulated by metabolic status or feeding conditions
      in Ya-fish.

PMID- 26311353
TI  - Dairy Consumption and Risk of Frailty in Older Adults: A Prospective Cohort
      Study.
AB  - OBJECTIVES: To examine the association between consumption of dairy products and
      risk of frailty in community-dwelling older adults. DESIGN: Prospective cohort
      study. SETTING: General population from the older cohort of the Study on
      Nutrition and Cardiovascular Risk in Spain. PARTICIPANTS: Community-dwelling
      adults aged 60 and older free of frailty at baseline (N = 1,871). MEASUREMENTS:
      From 2008 to 2010, food consumption was assessed using a validated diet history.
      Participants were examined again in 2012 to assess incident frailty, defined as
      at least three of the five Fried criteria (exhaustion, weakness, low physical
      activity, slow walking speed, unintentional weight loss). Adjusted odds ratios
      (OR) for the main confounders were obtained using logistic regression. RESULTS:
      During follow-up, 134 new cases of frailty were identified. Participants
      consuming seven or more servings per week of low-fat milk and yogurt had lower
      incidence of frailty (OR = 0.52; 95% confidence interval (CI) = 0.29-0.90; P for
      trend = .03) than those consuming less than one serving per week. Specifically,
      consumers of seven or more servings per week of low-fat milk and yogurt had less
      risk of slow walking speed (OR = 0.64, 95% CI = 0.44-0.92, P trend = .01) and of
      weight loss (OR = 0.54, 95% CI = 0.33-0.87, P trend = .02). Consuming seven or
      more servings per week of whole milk or yogurt (OR = 1.53, 95% CI = 0.90-2.60, P
      trend = .10) or of cheese (OR = 0.91, 95% CI = 0.52-1.61; P trend = .61) was not
      associated with incident frailty. CONCLUSION: Higher consumption of low-fat milk
      and yogurt was associated with lower risk of frailty and, specifically, of slow
      walking speed and weight loss. Current recommendations to prevent frailty include
      protein supplementation; thus, although experimental research is needed,
      increasing the consumption of low-fat yogurt and milk might prevent frailty in
      older adults.

PMID- 26311354
TI  - Changing perspective: The role of vestibular signals.
AB  - Social interactions depend on mechanisms such as the ability to take another
      person's viewpoint, i.e. visuo-spatial perspective taking. However, little is
      known about the sensorimotor mechanisms underpinning perspective taking. Because
      vestibular signals play roles in mental rotation and spatial cognition tasks and
      because damage to the vestibular cortex can disturb egocentric perspective,
      vestibular signals stand as important candidates for the sensorimotor foundations
      of perspective taking. Yet, no study merged natural full-body vestibular
      stimulations and explicit visuo-spatial perspective taking tasks in virtual
      environments. In Experiment 1, we combined natural vestibular stimulation on a
      rotatory chair with virtual reality to test how vestibular signals are processed
      to simulate the viewpoint of a distant avatar. While they were rotated,
      participants tossed a ball to a virtual character from the viewpoint of a distant
      avatar. Our results showed that vestibular signals influence perspective taking
      in a direction-specific way: participants were faster when their physical body
      rotated in the same direction as the mental rotation needed to take the avatar's
      viewpoint. In Experiment 2, participants realized 3D object mental rotations,
      which did not involve perspective taking, during the same whole-body vestibular
      stimulation. Our results demonstrated that vestibular stimulation did not affect
      3D object mental rotations. Altogether, these data indicate that vestibular
      signals have a direction-specific influence on visuo-spatial perspective taking
      (self-centered mental imagery), but not a general effect on mental imagery.
      Findings from this study suggest that vestibular signals contribute to one of the
      most crucial mechanisms of social cognition: understanding others' actions. 

PMID- 26311355
TI  - beta-catenin alteration is rare in hepatocellular carcinoma with steatohepatitic
      features: immunohistochemical and mutational study.
AB  - Hepatocellular carcinoma (HCC) with steatohepatitic features (steatohepatitic
      HCC, SH-HCC) is a histological subset of HCC, highly associated with metabolic
      disease and underlying steatohepatitis. Although it has distinct
      clinicopathologic characteristics, little is known about the immunophenotype or
      genetic characteristics of SH-HCC. We conducted an immunohistochemical analysis
      on a tissue microarray containing 197 HCCs (70 SH-HCCs and 127 conventional HCCs
      (C-HCCs)), focusing on proteins associated with genetic subtypes of HCC and those
      associated with non-alcoholic fatty liver disease (NAFLD) or NAFLD-associated
      HCC. We also investigated CTNNB1 mutations in 84 HCCs (31 SH-HCCs and 53 C-HCCs)
      to better characterize the SH-HCC. When compared to C-HCC, SH-HCC was
      characterized by a significantly lower incidence of nuclear accumulation of beta
      catenin (5.7 vs. 25.2 %, p < 0.001) and by a lower incidence of overexpression (H
      score = 300) of glutamine synthetase (4.3 vs. 26.0 %, p < 0.001). Multivariate
      logistic regression analysis revealed that the low rate of nuclear beta-catenin
      accumulation in SH-HCC was independent of background etiology, including
      underlying steatohepatitis (p < 0.001). In accordance with the
      immunohistochemical results, CTNNB1 mutations were less frequent in SH-HCC than C
      HCC (3.1 vs. 20.8 %, p < 0.048). Other notable findings included the ubiquitous
      expression of sonic hedgehog ligand in typical SH-HCC (100 %) and the less
      frequent expression of progenitor markers, such as SALL4 and EpCAM, in SH-HCC.
      These results indicate that SH-HCC as a subtype is not only characterized by
      morphology but also by distinct phenotypic and genetic traits.

PMID- 26311357
TI  - The Changing Epidemiology of Pediatric Endocarditis.
AB  - The epidemiology of infective endocarditis (IE) appears to be related to changes
      in the management of children with congenital heart disease (CHD) and the virtual
      disappearance of rheumatic heart disease. To better understand these changes, we
      divide the history into: I. The pre-surgical era, II. The early years of CHD
      surgical intervention, correlated with introduction of antibiotics, III. The
      modern era of cardiac interventions. Microbiologic changes include an early
      predominance of viridans streptococci and an overtaking by staphylococci.
      Additionally, there have been advances in imaging that allow earlier detection of
      IE and a reduction in IE-related mortality.

PMID- 26311358
TI  - Osteoarticular Infections in Children.
AB  - For a child with a suspected bone or joint infection, knowledge of the workup and
      initial therapy is important to provide quality care. Fever and pain are
      hallmarks of a pediatric osteoarticular infection, although occasionally the
      signs and symptoms can be more subtle. The use of C-reactive protein to diagnose
      and validate effective management of treatment has become standard. Multiple
      reports confirm the success of much shorter intravenous (IV) courses than
      traditionally taught. The ideal IV and oral antibiotic duration, as well as
      defining the markers indicating need for surgical intervention, are questions yet
      to be answered. 

PMID- 26311359
TI  - The effects of stress and affiliation on social decision-making: Investigating
      the tend-and-befriend pattern.
AB  - The prevalence of psychosocial stress in Western societies is constantly on the
      rise. Its influence on social decision-making, however, remains poorly
      understood. Whereas, it is known that stress triggers psychological and
      physiological defense mechanisms, indications of such patterns in social
      decisions are ambivalent. We sought to elucidate the underlying mechanisms of
      stress-induced social decisions. We recruited 145 men, who were individually
      exposed to either a psychosocial stressor or a control condition, while primed
      with affiliation by interacting either with members of an in- or an out-group. We
      found that stressed participants were less trusting and engaged in less costly
      punishment compared to the non-stressed control group. Interacting with out-group
      members led to less reciprocity and more spiteful punishment. There was no
      interaction between stress and the affiliation conditions in any of the used
      social-decision-making paradigms. Lastly, while stress-reactive cortisol levels
      had no effect on trust behavior, higher baseline cortisol was correlated with
      greater trust. Our findings suggest that previous ambiguities in data reported on
      the influence of stress on social decisions, namely tend-and-befriend behavior
      may have arisen through critical social confounds in the induction of stress.
      When controlling for potential social confounds, stress may trigger fight-or
      flight behavior as indicated by increased social anxiety. These findings
      highlight the considerable context-dependence of psychosocial stress and its
      effects on social behavior. 

PMID- 26311360
TI  - Latent trait cortisol (LTC) during pregnancy: Composition, continuity, change,
      and concomitants.
AB  - Individual differences in the activity of the hypothalamic pituitary adrenal
      (HPA) axis are often operationalized using summary measures of cortisol that are
      taken to represent stable individual differences. Here we extend our
      understanding of a novel latent variable approach to latent trait cortisol (LTC)
      as a measure of trait-like HPA axis function during pregnancy. Pregnant women
      (n=380) prospectively collected 8 diurnal saliva samples (4 samples/day, 2 days)
      within each trimester. Saliva was assayed for cortisol. Confirmatory factor
      analyses were used to fit LTC models to early morning and daytime cortisol. For
      individual trimester data, only the daytime LTC models had adequate fit. These
      daytime LTC models were strongly correlated between trimesters and stable over
      pregnancy. Daytime LTC was unrelated to the cortisol awakening response and the
      daytime slope but strongly correlated with the area under the curve from ground.
      The findings support the validity of LTC as a measure of cortisol during
      pregnancy and suggest that it is not affected by pregnancy-related changes in HPA
      axis function. 

PMID- 26311356
TI  - Prevention of Recurrent Staphylococcal Skin Infections.
AB  - Staphylococcus aureus infections pose a significant health burden. The emergence
      of community-associated methicillin-resistant S aureus has resulted in an
      epidemic of skin and soft tissue infections (SSTI), and many patients experience
      recurrent SSTI. As S aureus colonization is associated with subsequent infection,
      decolonization is recommended for patients with recurrent SSTI or in settings of
      ongoing transmission. S aureus infections often cluster within households, and
      asymptomatic carriers serve as reservoirs for transmission; therefore, a
      household approach to decolonization is more effective than measures performed by
      individuals alone. Novel strategies for the prevention of recurrent SSTI are
      needed. 

PMID- 26311361
TI  - Risk of familial classical Hodgkin lymphoma by relationship, histology, age, and
      sex: a joint study from five Nordic countries.
AB  - We aimed to provide the familial risk of classical Hodgkin lymphoma (HL) by
      relationship, histology, age at diagnosis, and sex. A cohort of 57,475 first
      degree relatives of 13,922 HL patients diagnosed between 1955 and 2009 in 5
      European countries was observed for HL incidence. The overall lifetime cumulative
      risk (CR) of HL in first-degree relatives of a patient with HL was 0.6%, which
      represents a threefold (standardized incidence ratio [SIR], 3.3; 95% confidence
      interval [CI], 2.8-3.9) increased risk over the general population risk. The risk
      in siblings (6.0-fold; 95% CI, 4.8- to 7.4-fold) was significantly higher than in
      parents and/or children (2.1-fold; 95% CI, 1.6- to 2.6-fold). Very high lifetime
      risk of HL was found for those with multiple affected first-degree relatives (13
      fold; 95% CI, 2.8- to 39-fold) and for same-sex twins (57-fold; 95% CI, 21- to
      125-fold). We found high familial risks between some concordant histologic
      subtypes of HL such as lymphocyte-rich (81-fold; 95% CI, 30- to 177-fold) and
      nodular sclerosis (4.6-fold; 95% CI, 2.9- to 7.0-fold) and also between some
      discordant subtypes. The familial risk in sisters (9.4-fold; 95% CI, 5.9- to 14
      fold) was higher than in brothers (4.5-fold; 95% CI, 2.9- to 6.7-fold) or unlike
      sex siblings (5.9-fold; 95% CI, 4.3- to 8.1-fold). The lifetime risk of HL was
      higher when first-degree relatives were diagnosed at early ages (before age 30
      years). This study provides tangible absolute risk estimates for relatives of HL
      patients, which can be used as a sex-, age-, and family history-based risk
      calculator for classical HL by oncologists and genetic counselors.

PMID- 26311366
TI  - Fifty-Fifth Annual Meeting of the Society for Psychophysiological Research:
      Westin Hotel, Seattle, Washington, USA September 30-October 4, 2015 Website:
      www.sprweb.org.

PMID- 26311367
TI  - The Present as the Past's Future: Past Presidents Panel.

PMID- 26311363
TI  - Cardiac rupture delayed for a week in an asymptomatic child following blunt
      trauma.
AB  - A two-year-old child was hit by a car outside his home and was immediately taken
      to hospital. There were no external injuries present over the body except two
      small abrasions on the occipital region of head. A computed tomography scan of
      the head was performed which revealed no cranio-cerebral injury. He was
      discharged from the hospital within few hours apparently well. The child was
      absolutely asymptomatic for a week, after which he suddenly died while playing at
      home. Autopsy revealed left ventricular free wall rupture and pericardial
      haematoma. This case report discusses the rare incidence of delayed cardiac
      rupture due to blunt trauma resulting in haemorrhagic tamponade in an
      asymptomatic child. 

PMID- 26311362
TI  - MLL leukemia induction by genome editing of human CD34+ hematopoietic cells.
AB  - Chromosomal rearrangements involving the mixed-lineage leukemia (MLL) gene occur
      in primary and treatment-related leukemias and confer a poor prognosis. Studies
      based primarily on mouse models have substantially advanced our understanding of
      MLL leukemia pathogenesis, but often use supraphysiological oncogene expression
      with uncertain implications for human leukemia. Genome editing using site
      specific nucleases provides a powerful new technology for gene modification to
      potentially model human disease, however, this approach has not been used to re
      create acute leukemia in human cells of origin comparable to disease observed in
      patients. We applied transcription activator-like effector nuclease-mediated
      genome editing to generate endogenous MLL-AF9 and MLL-ENL oncogenes through
      insertional mutagenesis in primary human hematopoietic stem and progenitor cells
      (HSPCs) derived from human umbilical cord blood. Engineered HSPCs displayed
      altered in vitro growth potentials and induced acute leukemias following
      transplantation in immunocompromised mice at a mean latency of 16 weeks. The
      leukemias displayed phenotypic and morphologic similarities with patient leukemia
      blasts including a subset with mixed phenotype, a distinctive feature seen in
      clinical disease. The leukemic blasts expressed an MLL-associated transcriptional
      program with elevated levels of crucial MLL target genes, displayed heightened
      sensitivity to DOT1L inhibition, and demonstrated increased oncogenic potential
      ex vivo and in secondary transplant assays. Thus, genome editing to create
      endogenous MLL oncogenes in primary human HSPCs faithfully models acute MLL
      rearranged leukemia and provides an experimental platform for prospective studies
      of leukemia initiation and stem cell biology in a genetic subtype of poor
      prognosis leukemia. 

PMID- 26311368
TI  - Transdiagnostic and Disorder-Specific Processes in Anxiety and Depression:
      Evidence from Psychophysiology.

PMID- 26311369
TI  - Affective Neurolinguistics: How Emotion Modulates Basic Language Processing.

PMID- 26311371
TI  - Adaptive Control: Neurocomputational Substrates and Implications for
      Neuropsychiatric Disease.

PMID- 26311372
TI  - Index to Abstract Descriptors.

PMID- 26311373
TI  - Auditory Predictions Induced by Extracted Sensorial Rules and by Intentional
      Actions.

PMID- 26311374
TI  - Equal, But Not the Same: Why Participant Diversity Matters in the Study of
      Physiology-Behavior Associations.

PMID- 26311375
TI  - Using Biobehavioral Profiles to Decrease Heterogeneity, Improve Specificity and
      Prediction of Risk.

PMID- 26311376
TI  - Brain Systems for Action Perception in Understanding Co-Speech Gesture And Signed
      Languages.

PMID- 26311377
TI  - Midline Frontal ERPS and Theta Phase Alignment.

PMID- 26311378
TI  - Potential Mechanisms for the Development and Maintenance of Threat Sensitivity In
      Anxiety.

PMID- 26311379
TI  - Altered States: Undergraduate-Driven EEG/ERP Research on Attention, Cognition,
      and Emotion.

PMID- 26311380
TI  - Psychophysiological Research in China and Japan.

PMID- 26311381
TI  - Emotion and Language in Interaction - Why and How Context Matters.

PMID- 26311382
TI  - Society for Psychophysiological Research, Abstracts for the Fifty-Fifth Annual
      Meeting, Westin Hotel, Seattle, Washington, USA, September 30-October 4, 2015.

PMID- 26311383
TI  - Psychophysiology Measures in Women's Health Research: Challenges and Creative
      Solutions.

PMID- 26311384
TI  - Predictive Coding Supports Sound Source Segregation.

PMID- 26311386
TI  - A Multi-Faceted Electrophysiological Lens on the Dynamics of Language
      Comprehension.

PMID- 26311385
TI  - Toward A Mechanistic Approach to Mindfulness Meditation Training.

PMID- 26311388
TI  - The Cognitive Neuroscience of Working Memory: Dynamics of Attention, Distraction,
      and Interference.

PMID- 26311387
TI  - Brain Stimulation to Enhance Processing Of Pleasant Stimuli: Evidence Across Two
      Methods and Three Measures.

PMID- 26311389
TI  - Mobile Brain/Body Imaging (MOBI), A New Field of Psychophysiological Research.

PMID- 26311390
TI  - Perturbative harmonic modulation of longitudinal electron-spin magnetization for
      short T(1) determination.
AB  - Longitudinally detected T1 measurement scheme (LOD-T1) is studied in detail. In
      contrast to the original work on LOD-T1, using high power microwave pulses, this
      work deals with general and practically frequent cases in which perfect inversion
      of the electron-spin magnetization is not feasible due to the effect of
      relaxation during microwave pulses. Theoretical studies, numerical simulations,
      and experiments reveal a pair of separate contributions of the dynamics of the
      longitudinal magnetization to the LOD signal, namely, the periodic modulation and
      the relaxation contributions. The latter alone which is of interest can be
      extracted to give relaxation curves. In addition, it is shown that T1 information
      can be obtained even when the available microwave power is so low that the
      electron magnetization can only be perturbatively modulated, at the cost of
      reduced sensitivity. To overcome this, a modified pulse sequence is proposed. In
      this new method, the pulse excitations are repeated during half a period of the
      resonance of the longitudinal detection circuit. The method is called the
      perturbative harmonic modulation method for longitudinally detected T1
      measurement (HM-LOD-T1). HM-LOD-T1 experiments are demonstrated in 2,2-diphenyl-1
      picrylhydrazyl (DPPH). 

PMID- 26311391
TI  - Integration in a nurse practitioner-led mental health service in rural Australia.
AB  - OBJECTIVE: Integration of mental health services is a prominent Australian mental
      health policy goal; however, there is little detail in the literature of how
      integrated mental health services are established or function. This study aimed
      to describe a nurse practitioner-led primary healthcare rural mental health
      service and evidence of how the service was integrated with other services and
      the community. DESIGN: This pragmatic exploratory study used case study
      methodology and analysed documents, quantitative data and qualitative data from
      individual and group semi-structured interviews and a 'stakeholder meeting'. The
      study was part of a formal evaluation of this nurse practitioner service.
      SETTING: Rural New South Wales. PARTICIPANTS: Twenty-one service providers and
      stakeholders. INTERVENTIONS: Introduction of a nurse practitioner led mental
      health service. MAIN OUTCOME MEASURES: Not applicable. RESULTS: Purposely sampled
      participants were interviewed. Documentary evidence included briefing notes,
      minutes and progress reports and provided important background information. Non
      identifiable aggregated client data were analysed. Thematic analysis of the
      qualitative data produced a description of how and why the service was
      established, a description of the service and its impact and three analytic
      themes providing evidence of integration. Challenges to integrating this service
      are also discussed. CONCLUSIONS: The service was highly regarded. It addressed
      the drug and alcohol and mental health needs of a vulnerable rural community. The
      inception and implementation of the service were community driven, led by a
      number of agencies supported by a steering committee and underpinned by a
      Partnership Agreement. The service demonstrated key features of integration
      alongside experiencing challenges in optimising integration with acute mental
      health services.

PMID- 26311392
TI  - Systematic analysis of gene expression pattern in has-miR-197 over-expressed
      human uterine leiomyoma cells.
AB  - INTRODUCTION: Our previous study showed that the expression of miR-197 in
      leiomyoma was down-regulated compared with myometrium. Further, miR-197 has been
      identified to affect uterine leiomyoma cell proliferation, apoptosis, and
      metastasis ability, though the responsible molecular mechanism has not been well
      elucidated. In this study, we sought to determine the expression patterns of miR
      197 targeted genes and to explore their potential functions, participating
      Pathways and the networks that are involved in the biological behavior of human
      uterine leiomyoma. METHODS: After transfection of human uterine leiomyoma cells
      with miR-197, we confirmed the expression level of miR-197 using quantitative
      real-time PCR (qRT-PCR), and we detected the gene expression profiles after miR
      197 over-expression through DNA microarray analysis. Further, we performed GO and
      Pathway analysis. The dominantly dys-regulated genes, which were up- or down
      regulated by more than 10-fold, compared with parental cells, were confirmed
      using qRT-PCR technology. RESULT: Compared with the control group, miR-197 was up
      regulated by 30-fold after miR-197 lentiviral transfection. The microarray data
      showed that 872 genes were dys-regulated by more than 2-fold in human uterine
      leiomyoma cells after miR-197 overexpression, including 537 up-regulated and 335
      down-regulated genes. The GO analysis indicated that the dys-regulated genes were
      primarily involved in response to stimuli, multicellular organ processes, and the
      signaling of biological progression. Further, Pathway analysis data showed that
      these genes participated in regulating several signaling Pathways, including the
      JAK/STAT signaling Pathway, the Toll-like receptor signaling Pathway, and
      cytokine-cytokine receptor interaction. The qRT-PCR results confirmed that 17 of
      the 66 selected genes, which were up- or down-regulated more than 10-fold by miR
      197, were consistent with the microarray results, including tumorigenesis-related
      genes, such as DRT7, SLC549, SFMBT2, FLJ37956, FBLN2, C10orf35, HOXD12, CACNG7,
      and LOC100134279. CONCLUSION: Our study explored gene expression patterns after
      miR-197 overexpression and confirmed 17 dominantly dys-regulated genes, which
      could expand the insights into the function of miR-197 and the molecular
      mechanisms during the development and progression of uterine leiomyomas. This
      study might afford new clues for understanding the pathogenesis of uterine
      leiomyomas, and it could likely provide a unique method for diagnosing or
      predicting prognosis in the clinical treatment of leiomyoma.

PMID- 26311393
TI  - Orbito-frontal cortex and thalamus volumes in obsessive-compulsive disorder
      before and after pharmacotherapy.
AB  - In the present study, we focused on the key brain regions, OFC and thalamus, to
      investigate the roles of antiobsessional agents on volume changes of these brain
      regions after 12 weeks of anti-obsessional treatment in patients with obsessive
      compulsive disorder (OCD). Fourteen patients with OCD and the same number of
      healthy controls were included in the study. At baseline, the volumes of the OFC
      and thalamus were compared by using magnetic resonance imaging (MRI) between
      groups. The volumes of OFC and thalamus were evaluated before and after the anti
      obsessional drug treatment solely in the patient group. Our study revealed that
      thalamus volumes were reduced statistically significantly throughout the
      treatment period. However, we found that OFC volumes did not change statistically
      significantly throughout the treatment period. In summary, our study found that
      anti-obsessional drug treatment had an effect on thalamus volumes throughout the
      treatment period for both sides but not on OFC volumes. However, future studies
      with larger sample are required.

PMID- 26311394
TI  - Discriminative multi-task feature selection for multi-modality classification of
      Alzheimer's disease.
AB  - Recently, multi-task based feature selection methods have been used in multi
      modality based classification of Alzheimer's disease (AD) and its prodromal
      stage, i.e., mild cognitive impairment (MCI). However, in traditional multi-task
      feature selection methods, some useful discriminative information among subjects
      is usually not well mined for further improving the subsequent classification
      performance. Accordingly, in this paper, we propose a discriminative multi-task
      feature selection method to select the most discriminative features for multi
      modality based classification of AD/MCI. Specifically, for each modality, we
      train a linear regression model using the corresponding modality of data, and
      further enforce the group-sparsity regularization on weights of those regression
      models for joint selection of common features across multiple modalities.
      Furthermore, we propose a discriminative regularization term based on the intra
      class and inter-class Laplacian matrices to better use the discriminative
      information among subjects. To evaluate our proposed method, we perform extensive
      experiments on 202 subjects, including 51 AD patients, 99 MCI patients, and 52
      healthy controls (HC), from the baseline MRI and FDG-PET image data of the
      Alzheimer's Disease Neuroimaging Initiative (ADNI). The experimental results show
      that our proposed method not only improves the classification performance, but
      also has potential to discover the disease-related biomarkers useful for
      diagnosis of disease, along with the comparison to several state-of-the-art
      methods for multi-modality based AD/MCI classification.

PMID- 26311395
TI  - Abnormal prefrontal cortex resting state functional connectivity and severity of
      internet gaming disorder.
AB  - Internet Gaming Disorder (IGD) among adolescents has become an important public
      concern and gained more and more attention internationally. Recent studies
      focused on IGD and revealed brain abnormalities in the IGD group, especially the
      prefrontal cortex (PFC). However, the role of PFC-striatal circuits in pathology
      of IGD remains unknown. Twenty-five adolescents with IGD and 21 age- and gender
      matched healthy controls were recruited in our study. Voxel-based morphometric
      (VBM) and functional connectivity analysis were employed to investigate the
      abnormal structural and resting-state properties of several frontal regions in
      individuals with online gaming addiction. Relative to healthy comparison
      subjects, IGD subjects showed significant decreased gray matter volume in PFC
      regions including the bilateral dorsolateral prefrontal cortex (DLPFC),
      orbitofrontal cortex (OFC), anterior cingulate cortex (ACC) and the right
      supplementary motor area (SMA) after controlling for age and gender effects. We
      chose these regions as the seeding areas for the resting-state analysis and found
      that IGD subjects showed decreased functional connectivity between several
      cortical regions and our seeds, including the insula, and temporal and occipital
      cortices. Moreover, significant decreased functional connectivity between some
      important subcortical regions, i.e., dorsal striatum, pallidum, and thalamus, and
      our seeds were found in the IGD group and some of those changes were associated
      with the severity of IGD. Our results revealed the involvement of several PFC
      regions and related PFC-striatal circuits in the process of IGD and suggested IGD
      may share similar neural mechanisms with substance dependence at the circuit
      level.

PMID- 26311396
TI  - Semantic congruency and the (reversed) Colavita effect in children and adults.
AB  - When presented with auditory, visual, or bimodal audiovisual stimuli in a
      discrimination task, adults tend to ignore the auditory component in bimodal
      stimuli and respond to the visual component only (i.e., Colavita visual dominance
      effect). The same is true for older children, whereas young children are
      dominated by the auditory component of bimodal audiovisual stimuli. This suggests
      a change of sensory dominance during childhood. The aim of the current study was
      to investigate, in three experimental conditions, whether children and adults
      show sensory dominance when presented with complex semantic stimuli and whether
      this dominance can be modulated by stimulus characteristics such as semantic
      (in)congruency, frequency of bimodal trials, and color information. Semantic
      (in)congruency did not affect the magnitude of the auditory dominance effect in 6
      year-olds or the visual dominance effect in adults, but it was a modulating
      factor of the visual dominance in 9-year-olds (Conditions 1 and 2). Furthermore,
      the absence of color information (Condition 3) did not affect auditory dominance
      in 6-year-olds and hardly affected visual dominance in adults, whereas the visual
      dominance in 9-year-olds disappeared. Our results suggest that (a) sensory
      dominance in children and adults is not restricted to simple lights and sounds,
      as used in previous research, but can be extended to semantically meaningful
      stimuli and that (b) sensory dominance is more robust in 6-year-olds and adults
      than in 9-year-olds, implying a transitional stage around this age. 

PMID- 26311397
TI  - The effect of fine and grapho-motor skill demands on preschoolers' decoding
      skill.
AB  - Previous correlational research has found indications that fine motor skills
      (FMS) link to early reading development, but the work has not demonstrated
      causality. We manipulated 51 preschoolers' FMS while children learned to decode
      letters and nonsense words in a within-participants, randomized, and
      counterbalanced single-factor design with pre- and posttesting. In two
      conditions, children wrote with a pencil that had a conical shape fitted to the
      end filled with either steel (impaired writing condition) or polystyrene (normal
      writing condition). In a third control condition, children simply pointed at the
      letters with the light pencil as they learned to read the words (pointing
      condition). Results indicate that children learned the most decoding skills in
      the normal writing condition, followed by the pointing and impaired writing
      conditions. In addition, working memory, phonemic awareness, and grapho-motor
      skills were generally predictors of decoding skill development. The findings
      provide experimental evidence that having lower FMS is disadvantageous for
      reading development. 

PMID- 26311399
TI  - Identification of the chemical constituents of Chinese medicine Yi-Xin-Shu
      capsule by molecular feature orientated precursor ion selection and tandem mass
      spectrometry structure elucidation.
AB  - The incomplete identification of the chemical components of traditional Chinese
      medicinal formula has been one of the bottlenecks in the modernization of
      traditional Chinese medicine. Tandem mass spectrometry has been widely used for
      the identification of chemical substances. Current automatic tandem mass
      spectrometry acquisition, where precursor ions were selected according to their
      signal intensity, encounters a drawback in chemical substances identification
      when samples contain many overlapping signals. Compounds in minor or trace
      amounts could not be identified because most tandem mass spectrometry information
      was lost. Herein, a molecular feature orientated precursor ion selection and
      tandem mass spectrometry structure elucidation method for complex Chinese
      medicine chemical constituent analysis was developed. The precursor ions were
      selected according to their two-dimensional characteristics of retention times
      and mass-to-charge ratio ranges from herbal compounds, so that all precursor ions
      from herbal compounds were included and more minor chemical constituents in
      Chinese medicine were identified. Compared to the conventional automatic tandem
      mass spectrometry setups, the approach is novel and can overcome the drawback for
      chemical substances identification. As an example, 276 compounds from the Chinese
      Medicine of Yi-Xin-Shu capsule were identified. 

PMID- 26311398
TI  - Hyaluronan modulates TRPV1 channel opening, reducing peripheral nociceptor
      activity and pain.
AB  - Hyaluronan (HA) is present in the extracellular matrix of all body tissues,
      including synovial fluid in joints, in which it behaves as a filter that buffers
      transmission of mechanical forces to nociceptor nerve endings thereby reducing
      pain. Using recombinant systems, mouse-cultured dorsal root ganglia (DRG) neurons
      and in vivo experiments, we found that HA also modulates polymodal transient
      receptor potential vanilloid subtype 1 (TRPV1) channels. HA diminishes heat, pH
      and capsaicin (CAP) responses, thus reducing the opening probability of the
      channel by stabilizing its closed state. Accordingly, in DRG neurons, HA
      decreases TRPV1-mediated impulse firing and channel sensitization by bradykinin.
      Moreover, subcutaneous HA injection in mice reduces heat and capsaicin
      nocifensive responses, whereas the intra-articular injection of HA in rats
      decreases capsaicin joint nociceptor fibres discharge. Collectively, these
      results indicate that extracellular HA reduces the excitability of the ubiquitous
      TRPV1 channel, thereby lowering impulse activity in the peripheral nociceptor
      endings underlying pain. 

PMID- 26311401
TI  - Research on the Diffusion Law of Oncomelania Along with the Flow Through a Side
      weir.
AB  - Schistosomiasis is a parasitic disease mostly found in areas along the Changjiang
      River, Oncomelanias is the only intermediate host of schistosomiasis. Oncomelania
      entering into farmland or the residential zones through the flood discharge or
      irrigation system is the main reason of spreading schistosomiasis. Therefore it
      is most essential and effective way to control diffusion of oncomelanias along
      with flow for preventing epidemic of schistosomiasis disease. In order to
      simulate the flood discharge when the river dike break or the flow from main to
      branch channel, a side-weir flow system is set up in this paper, And furtherly
      the flow characteristic is studied by experiment and mathematical modeling,
      Finally the research on the diffusion law of oncomelania along with side-weir
      flow is carried out using the experimental test. The results show that
      oncomelanias do not equally distribute at floodplain areas, but place where flow
      velocity is small, i.e. in the vortex areas during oncomelanias moving along with
      side-weir flow. The settling positions of oncomelanias are obtained, Which lay a
      good foundation for eliminating oncomelanias. 

PMID- 26311402
TI  - Combination of amniotic epithelial cells with NDGA promotes the survival of
      transplanted AECs in spinal cord-injured rats.
AB  - Our previous research has shown that seeding amniotic epithelial cells (AECs) in
      chemically extracted acellular muscle scaffold (CEAMC) better promotes the
      functional recovery of spinal cord injury (SCI) than scaffold alone. However, the
      massive death of transplanted cells, which is related to early inflammatory
      response, is still a problem in cell therapy. Our previous study proved that
      nordihydroguaiaretic acid (NDGA) inhibits inflammation after SCI. In this study,
      we tested a strategy of combining the early administration of NDGA and the
      transplantation of AEC-seeded CEAMC to treat SCI. The results showed that simply
      increasing the number of surviving AECs had no significant benefits in SCI
      therapy, but NDGA administration ameliorated transplanted AEC survival
      demonstrating the potential value of NDGA in the cellular transplantation
      treatment of SCI. 

PMID- 26311400
TI  - State of the art systematic review of bone disease in anorexia nervosa.
AB  - OBJECTIVE: Low bone mineral density (BMD) is a known consequence of anorexia
      nervosa (AN) and is particularly concerning during adolescence, a critical time
      for bone accrual. A comprehensive synthesis of available data regarding impaired
      bone health, its determinants, and associated management strategies in AN is
      currently lacking. This systematic review aims to synthesize information from key
      physiologic and prospective studies and trials, and provide a thorough
      understanding of impaired bone health in AN and its management. METHOD: Search
      terms included "anorexia nervosa" AND "bone density" for the period 1995-2015,
      limited to articles in English. Papers were screened manually based on journal
      impact factor, sample size, age of participants, and inclusion of a control
      group. When necessary, we included seminal papers published before 1995. RESULTS:
      AN leads to low BMD, impaired bone quality and increased fracture risk. Important
      determinants are low lean mass, hypogonadism, IGF-1 deficiency, and alterations
      in other hormones that impact bone health. Weight gain and menses restoration are
      critical for improving bone outcomes in AN. Physiologic estrogen replacement as
      the transdermal patch was shown to increase bone accrual in one study in
      adolescent females with AN; however, residual deficits persist. Bisphosphonates
      are potentially useful in adults with AN. DISCUSSION: To date, evidence suggests
      that the safest and most effective strategy to improve bone health in AN is
      normalization of weight with restoration of menses. Pharmacotherapies that show
      promise include physiologic estradiol replacement (as the transdermal estradiol
      patch), and in adults, bisphosphonates. Further studies are necessary to
      determine the best strategies to normalize BMD in AN.

PMID- 26311403
TI  - Fauna Europaea: Mollusca - Bivalvia.
AB  - Fauna Europaea provides a public web-service with an index of scientific names
      (including important synonyms) 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 the Mollusca-Bivalvia, data from 5 families
      (Margaritiferidae, Unionidae, Sphaeriidae, Cyrenidae, Dreissenidae) containing 55
      species are included in this paper. European freshwater bivalves belong to the
      Orders Unionoida and Cardiida. All the European unionoids are included in the
      superfamily Unionoidea, the freshwater mussels or naiads. The European cardiids
      belong to the following three superfamilies: Cardioidea, Cyrenoidea and
      Dreissenoidea. Among the Unionoidea there are the most imperilled animal groups
      on the planet while the Cardioidea includes the cosmopolitan genus Pisidium, the
      Cyrenoidea the Asiatic clam (Corbiculafluminea) and the Dreissenoidea the famous
      invasive zebra mussel (Dreissenapolymorpha). Basic information is summarized on
      their taxonomy and biology. Tabulations include a complete list of the current
      estimated families, genera and species. 

PMID- 26311404
TI  - Intrauterine adhesion after transvaginal ultrasound-guided radiofrequency
      myolysis.
AB  - Transvaginal ultrasound-guided radiofrequency myolysis offers an alternative to
      surgery for symptomatic uterine myomas, with encouraging efficacy and safety,
      suggesting low complication rates. This case study describes the first reported
      intrauterine adhesion after transvaginal ultrasound-guided radiofrequency
      myolysis. Women who desire further pregnancy should be warned about the
      particular risk of intrauterine adhesion of radiofrequency myolysis. 

PMID- 26311405
TI  - Shared mental healthcare and somatization: changes in patient symptoms and
      disability.
AB  - AIM: To describe the symptoms and functional changes in patients with high levels
      of somatization who were referred to an outpatient, multidisciplinary, shared
      mental healthcare (SMHC) service that primarily offered cognitive behavioural
      therapy. Second, we wished to compare the levels of somatization in this
      outpatient clinical sample with previously published community norms. BACKGROUND:
      Somatization is common in primary care, and it can lead to significant
      impairment, disproportionate resource use, and poses a challenge for management.
      METHODS: All the patients (18+ years, n=508) who attended three or more treatment
      sessions in SMHC primary care over a seven-year period were eligible for
      inclusion to this pre-post study. Self-report measures included the Patient
      Health Questionnaire's somatic symptom severity scale (PHQ-15) and the World
      Health Organization Disability Assessment Schedule (WHODAS II). Normative
      comparisons were used to assess the degree of symptoms and functional changes.
      FINDINGS: Clinically significant levels of somatization before treatment were
      common (n=138, 27.2%) and were associated with a significant reduction in somatic
      symptom severity (41.3% reduction; P<0.001) and disability (44% reduction;
      P<0.001) after treatment. Patients' levels of somatic symptom severity and
      disability approached but did not quite reach the community sample norms
      following treatment. Multidisciplinary short-term SMHC was associated with
      significant improvement in patient symptoms and disability, and shows promise as
      an effective treatment for patients with high levels of somatization. Including a
      control group would allow more confidence regarding the conclusions about the
      effectiveness of SMHC for patients impaired by somatization.

PMID- 26311406
TI  - A low-phase-noise 18 GHz Kerr frequency microcomb phase-locked over 65 THz.
AB  - Laser frequency combs are coherent light sources that simultaneously provide
      pristine frequency spacings for precision metrology and the fundamental basis for
      ultrafast and attosecond sciences. Recently, nonlinear parametric conversion in
      high-Q microresonators has been suggested as an alternative platform for optical
      frequency combs, though almost all in 100 GHz frequencies or more. Here we report
      a low-phase-noise on-chip Kerr frequency comb with mode spacing compatible with
      high-speed silicon optoelectronics. The waveguide cross-section of the silicon
      nitride spiral resonator is designed to possess small and flattened group
      velocity dispersion, so that the Kerr frequency comb contains a record-high
      number of 3,600 phase-locked comb lines. We study the single-sideband phase noise
      as well as the long-term frequency stability and report the lowest phase noise
      floor achieved to date with -130 dBc/Hz at 1 MHz offset for the 18 GHz Kerr comb
      oscillator, along with feedback stabilization to achieve frequency Allan
      deviations of 7 * 10(-11) in 1 s. The reported system is a promising compact
      platform for achieving self-referenced Kerr frequency combs and also for high
      capacity coherent communication architectures. 

PMID- 26311407
TI  - OPA1-related disorders: Diversity of clinical expression, modes of inheritance
      and pathophysiology.
AB  - Mutations in the Optic Atrophy 1 gene (OPA1) were first identified in 2000 as the
      main cause of Dominant Optic Atrophy, a disease specifically affecting the
      retinal ganglion cells and the optic nerve. Since then, an increasing number of
      symptoms involving the central, peripheral and autonomous nervous systems, with
      considerable variations of age of onset and severity, have been reported in OPA1
      patients. This variety of phenotypes is attributed to differences in the effects
      of OPA1 mutations, to the mode of inheritance, which may be mono- or bi-allelic,
      and eventually to somatic mitochondrial DNA mutations. The diversity of the
      pathophysiological mechanisms involved in OPA1-related disorders is linked to the
      crucial role played by OPA1 in the maintenance of mitochondrial structure, genome
      and function. The neurological expression of these disorders highlights the
      importance of mitochondrial dynamics in neuronal processes such as
      dendritogenesis, axonal transport, and neuronal survival. Thus, OPA1-related
      disorders may serve as a paradigm in the wider context of neurodegenerative
      syndromes, particularly for the development of novel therapeutic strategies
      against these diseases. 

PMID- 26311408
TI  - Vascular dysfunction in the pathogenesis of Alzheimer's disease--A review of
      endothelium-mediated mechanisms and ensuing vicious circles.
AB  - Late-onset dementia is a major health concern in the ageing population.
      Alzheimer's disease (AD) accounts for the largest proportion (65-70%) of dementia
      cases in the older population. Despite considerable research effort, the
      pathogenesis of late-onset AD remains unclear. Substantial evidence suggests that
      the neurodegenerative process is initiated by chronic cerebral hypoperfusion
      (CCH) caused by ageing and cardiovascular conditions. CCH causes reduced oxygen,
      glucose and other nutrient supply to the brain, with direct damage not only to
      the parenchymal cells, but also to the blood-brain barrier (BBB), a key mediator
      of cerebral homeostasis. BBB dysfunction mediates the indirect neurotoxic effects
      of CCH by promoting oxidative stress, inflammation, paracellular permeability,
      and dysregulation of nitric oxide, a key regulator of regional blood flow. As
      such, BBB dysfunction mediates a vicious circle in which cerebral perfusion is
      reduced further and the neurodegenerative process is accelerated. Endothelial
      interaction with pericytes and astrocytes could also play a role in the process.
      Reciprocal interactions between vascular dysfunction and neurodegeneration could
      further contribute to the development of the disease. A comprehensive overview of
      the complex scenario of interacting endothelium-mediated processes is currently
      lacking, and could prospectively contribute to the identification of adequate
      therapeutic interventions. This study reviews the current literature of in vitro
      and ex vivo studies on endothelium-mediated mechanisms underlying vascular
      dysfunction in AD pathogenesis, with the aim of presenting a comprehensive
      overview of the complex network of causative relationships. Particular emphasis
      is given to vicious circles which can accelerate the process of neurovascular
      degeneration. 

PMID- 26311409
TI  - Coronal tibiofemoral subluxation in knee osteoarthritis.
AB  - OBJECTIVE: To analyze knees in varying stages of osteoarthritis (OA) for the
      presence of coronal tibiofemoral (CTF) subluxation and to determine if CTF
      subluxation severity is related to knee OA worsening. METHODS: We retrospectively
      evaluated CTF subluxation and limb alignment in 113 patients with different
      stages of knee OA who were being considered for an arthroplasty procedure. Knee
      OA was classified as "mild" or "severe" according to Kellgren-Lawrence scale. CTF
      subluxation was measured in the study groups and in 40 knees of healthy controls
      using software developed specifically on the basis of Iterative Closest Point
      mathematical algorithm. RESULTS: Mean CTF subluxation in "mild OA" and "severe
      OA" groups was 3.5% (+/-2) and 3.5 % (+/-5) of the tibial plateau, respectively.
      For both the mild and severe OA groups, CTF subluxation was significantly
      increased compared to the 1.4% (+/-1) CTF subluxation in the control group, (p <
      0.0001) and (p = 0.012), respectively. However, there was no significant
      difference in CTF subluxation between the mild OA and severe OA groups (p =
      0.75). Limb varus malalignment in mild OA and severe OA groups was 3.6 degrees 
      (+/-2.2) and 5.3 degrees  (+/-2.6), respectively. Both significantly increased
      comparing to the 1 degrees  (+/-0.7) control group alignment (p < 0.0001). Varus
      malalignment in the severe OA group was significantly increased comparing to the
      mild OA group (p = 0.0003). CONCLUSIONS: CTF subluxation is a radiographic
      finding related to knee OA which occurs mainly in the early stages of the
      osteoarthritic process and stagnates as OA progresses.

PMID- 26311410
TI  - Water: Promising Opportunities For Tunable All-dielectric Electromagnetic
      Metamaterials.
AB  - We reveal an outstanding potential of water as an inexpensive, abundant and bio
      friendly high-refractive-index material for creating tunable all-dielectric
      photonic structures and metamaterials. Specifically, we demonstrate thermal,
      mechanical and gravitational tunability of magnetic and electric resonances in a
      metamaterial consisting of periodically positioned water-filled reservoirs. The
      proposed water-based metamaterials can find applications not only as cheap and
      ecological microwave devices, but also in optical and terahertz metamaterials
      prototyping and educational lab equipment. 

PMID- 26311411
TI  - Myoferlin plays a key role in VEGFA secretion and impacts tumor-associated
      angiogenesis in human pancreas cancer.
AB  - Pancreatic ductal adenocarcinoma is one of the most deadly forms of cancers with
      no satisfactory treatment to date. Recent studies have identified myoferlin, a
      ferlin family member, in human pancreas adenocarcinoma where its expression was
      associated to a bad prognosis. However, the function of myoferlin in pancreas
      adenocarcinoma has not been reported. In other cell types, myoferlin is involved
      in several key plasma membrane processes such as fusion, repair, endocytosis and
      tyrosine kinase receptor activity. In this study, we showed that myoferlin
      silencing in BxPC-3 human pancreatic cancer cells resulted in the inhibition of
      cell proliferation in vitro and in a significant reduction of the tumor volume in
      chick chorioallantoic membrane assay. In addition to be smaller, the tumors
      formed by the myoferlin-silenced cells showed a marked absence of functional
      blood vessels. We further demonstrated that this effect was due, at least in
      part, to an inhibition of VEGFA secretion by BxPC-3 myoferlin-silenced cells.
      Using immunofluorescence and electron microscopy, we linked the decreased VEGFA
      secretion to an impairment of VEGFA exocytosis. The clinical relevance of our
      results was further strengthened by a significant correlation between myoferlin
      expression in a series of human pancreatic malignant lesions and their angiogenic
      status evaluated by the determination of the blood vessel density. 

PMID- 26311412
TI  - Retinoid roles in blocking hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a major health issue in many countries. The
      prognosis of HCC is still poor due to its high recurrence rate and its resistance
      to chemotherapy. Retinoids have long been known to have a connection with liver
      diseases, including HCC. Many experimental and clinical investigations have
      demonstrated associations between retinoids and hepatic disease, including the
      loss of retinoid activity in HCC cell lines and decreased hepatic retinoid stores
      and altered retinoid signaling in patients with cirrhosis and HCC. Based on these
      findings, preclinical and clinical investigations of retinoid effects on HCC have
      been undertaken. Recently, clinical trial results for the use of a synthetic
      retinoid, acyclic retinoid (ACR), to prevent HCC recurrence were published. In
      addition, extensive experimental studies on the action of retinoids in liver
      disease, including chronic viral hepatitis and non-alcoholic fatty liver disease
      (NAFLD), which lead to HCC have been performed. In the first section of this
      review, we will summarize the effectiveness and roles of retinoid for treating
      liver disease and blocking HCC. Subsequently, we will focus on ACR actions in
      blocking HCC. 

PMID- 26311414
TI  - Classical imaging findings in spinal subdural hematoma - "Mercedes-Benz" and
      "Cap" signs.

PMID- 26311413
TI  - Insights into electron leakage in the reaction cycle of cytochrome P450 BM3
      revealed by kinetic modeling and mutagenesis.
AB  - As a single polypeptide, cytochrome P450 BM3 fuses oxidase and reductase domains
      and couples each domain's function to perform catalysis with exceptional activity
      upon binding of substrate for hydroxylation. Mutations introduced into the enzyme
      to change its substrate specificity often decrease coupling efficiency between
      the two domains, resulting in unproductive consumption of cofactors and formation
      of water and/or reactive species. This phenomenon can correlate with leakage, in
      which P450 BM3 uses electrons from NADPH to reduce oxygen to water and/or
      reactive species even without bound substrate. The physical basis for leakage is
      not yet well understood in this particular member of the cytochrome P450 family.
      To clarify the relationship between leakage and coupling, we used simulations to
      illustrate how different combinations of kinetic parameters related to substrate
      free consumption of NADPH and substrate hydroxylation can lead to either minimal
      effects on coupling or a dramatic decrease in coupling as a result of leakage. We
      explored leakage in P450 BM3 by introducing leakage-enhancing mutations and
      combining these mutations to assess whether doing so increases leakage further.
      The variants in this study provide evidence that while a transition to high spin
      may be vital for coupled hydroxylation, it is not required for enhanced leakage;
      substrate binding and the consequent shift in spin state are not necessary as a
      redox switch for catalytic oxidation of NADPH. Additionally, the variants in this
      study suggest a tradeoff between leakage and stability and thus evolvability, as
      the mutations we investigated were far more deleterious than other mutations that
      have been used to change substrate specificity. 

PMID- 26311415
TI  - Onset of optimal P2Y12-ADP receptor blockade after ticagrelor and prasugrel
      intake in Non-ST elevation acute coronary syndrome.
AB  - Pretreatment with a loading dose (LD) of clopidogrel or ticagrelor before
      percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) is
      supported by the guidelines, but debated following a recent meta-analysis on
      clopidogrel pretreatment and the ACCOAST trial. In this trial prasugrel
      pretreatment failed to reduce ischaemic events. The timing of optimal platelet
      reactivity (PR) inhibition of ticagrelor and prasugrel in non ST-elevation ACS
      (NSTE ACS) is yet undetermined. In the present study, we aimed to investigate the
      delay required to reach optimal PR inhibition in NSTE ACS following a LD of
      ticagrelor or prasugrel. Consecutive patients undergoing PCI for NSTE ACS were
      randomised in this monocentre study. The Vasodilator-phosphoprotein index (VASP)
      was used to measure PR before the LD and then at 30 minutes, 1, 2, 4 and 24 hours
      (h) post-LD. Optimal PR inhibition was defined as a VASP < 50%. We randomised 24
      patients to ticagrelor or prasugrel LD. One hour after the LD, 29% of patients
      had a VASP > 50% (ticagrelor and prasugrel: 25 vs 33%; p=0.7). Optimal PR
      inhibition was obtained 2 h after the LD in both groups (12/12 with ticagrelor
      and 11/12 with prasugrel). At that time, the mean VASP index was 19 +/- 16%
      (95%CI: 12-25). Maximal PR inhibition was reached after 4 h: 11 +/- 10% (95%CI: 6
      15). In NSTE ACS undergoing PCI a LD of ticagrelor or prasugrel given during the
      procedure provides optimal P2Y12-ADP receptor blockade in 2 h and maximal
      inhibition within 4 h.

PMID- 26311416
TI  - Understanding the relative importance of global dengue risk factors.
AB  - Dengue is a mosquito-transmitted viral infection of major international public
      health concern. Global environmental and socio-economic change has created ideal
      conditions for the global expansion of dengue transmission. Innovative modelling
      tools help in understanding the global determinants of dengue risk and the
      relative impact of environmental and socio-economic factors on dengue
      transmission and spread. While climatic factors may act as a limiting factor on
      the global scale, other processes may play a dominant role at the local level.
      Understanding the spatial scales at which environmental and socio-economic
      factors dominate can help to target appropriate dengue control and prevention
      strategies. 

PMID- 26311417
TI  - Assessing geriatric vulnerability for post emergency department adverse outcomes:
      challenges abound while progress is slow.

PMID- 26311418
TI  - Re: Saving the critically injured trauma patient.

PMID- 26311419
TI  - Rats (Rattus norvegicus) flexibly retrieve objects' non-spatial and spatial
      information from their visuospatial working memory: effects of integrated and
      separate processing of these features in a missing-object recognition task.
AB  - After being trained to find a previous missing object within an array of four
      different objects, rats received occasional probe trials with such test arrays
      rotated from that of their respective three-object study arrays. Only animals
      exposed to each object's non-spatial features consistently paired with both its
      spatial features (feeder's relative orientation and direction) in the first
      experiment or with only feeder's relative orientation in the second experiment
      (Fixed Configuration groups) were adversely affected by probe trial test array
      rotations. This effect, however, was less persistent for this group in the second
      experiment but re-emerged when objects' non-spatial features were later rendered
      uninformative. Animals that had both types of each object's features randomly
      paired over trials but not between a trial's study and test array (Varied
      Configuration groups) were not adversely affected on probe trials but improved
      their missing-object recognition in the first experiment. These findings suggest
      that the Fixed Configuration groups had integrated each object's non-spatial with
      both (in Experiment 1) or one (in Experiment 2) of its spatial features to
      construct a single representation that they could not easily compare to any
      object in a rotated probe test array. The Varied Configuration groups must
      maintain separate representations of each object's features to solve this task.
      This prevented them from exhibiting such adverse effects on rotated probe trial
      test arrays but enhanced the rats' missing-object recognition in the first
      experiment. We discussed how rats' flexible use (retrieval) of encoded
      information from their visuospatial working memory corresponds to that of humans'
      visuospatial memory in object change detection and complex object recognition
      tasks. We also discussed how foraging-specific factors may have influenced each
      group's performance in this task. 

PMID- 26311422
TI  - Anti-Inflammatory and Pro-Resolving Effects of N-3 PUFA in Cancers: Structures
      and Mechanisms.
AB  - As an important hallmark in cancer progress, inflammation attracts more and more
      interests in recent years. Lots of evidences support the positive effect of n-3
      PUFA in inflammation-associated diseases, the supplement of these fatty acids is
      thought to be promising in the prevention and treatment of cancers. In this
      review, we summarize some current knowledge of the mechanisms by which n-3 PUFA
      are thought to attenuate cancer associated inflammation, and we also introduce
      the current situation of n-3 PUFA in clinic. 

PMID- 26311420
TI  - Surveillance for early stages of colon cancer: potentials for optimizing follow
      up protocols.
AB  - BACKGROUND: Although several meta-analyses showed the positive effects of follow
      up on the prognosis of colon cancer (CC), international guidelines are not in
      accordance on appropriate tests and their time frequency to optimize
      surveillance. Furthermore, stratified strategies based upon risk grading have not
      been implemented. This approach may be useful to rationalize resources. METHODS:
      From 2006, all patients operated for an early stage CC (I, IIA, IIB) according to
      the 7th edition of the AJCC-2010 classification entered in a prospective
      surveillance program in accordance to our local guidelines. Patients who
      underwent surgical resection after 2009 have been excluded to guarantee at least
      a 5-year follow-up. Classic histopathologic prognostic factors such as grade, T
      and N status, lymphatic and vascular invasion were assessed. Moreover, tumor
      budding and tumor-to-stroma proportion were evaluated. RESULTS: We had complete
      records of 196 patients. Distribution was as follows: 65 (33.2%) in stage I, 122
      (62.2%) in stage IIA, and 9 (4.6%) in stage IIB. Eleven patients (5.6%) had a
      disease recurrence (local or distant). The median recurrence time was 20 months
      (range 6-48). Nine patients (82%) had recurrence with 24 months, and 91% were
      asymptomatic and detected by ultrasound or CT scan. According to the log-rank
      test, the risk factors with significant effect on the disease-free survival (DFS)
      were the number of lymph nodes <12 (p = 0.027) and the vascular invasion (p =
      0.021), while for the overall (OS), only the vascular invasion was significant (p
      = 0.043). By the univariate and multivariate analyses, DSF was significantly
      lower in patients with less than 12 nodes removed, with vascular invasion, and
      with left of double cancer. OS was negatively affected only by vascular invasion
      despite the hazard ratios were similar to DSF. Stage IIB was associated with a
      threefold-increased risk of reduced OS and DSF. CONCLUSIONS: Stages I and IIA
      appear to behave similarly and should be considered as true early stages. The
      detection of fibrosis and budding do not seem to add valuable information for
      prognosis. In early CC stages, the surveillance program should be maximized
      within the first two years.

PMID- 26311423
TI  - Characterization and Immunological Evaluation of Low-Molecular- Weight Alginate
      Derivatives.
AB  - Alginate is a naturally occurring acidic linear polysaccharide obtained from
      marine brown seaweed. Low molecular weight structurally diverse derivatives and
      oligosaccharides derived from alginate have shown various tremendous biological
      and pharmacological activities. It has been demonstrated that immuno-inflammation
      is involved in many prevalent human diseases, such as cancer, severe infection
      and neurodegeneration. Given the activities of marine natural products in the
      regulation of immune responses, increasing efforts are being made toward the
      development of lowmolecular- weight natural compounds that aid in the prevention
      and treatment of immune- and inflammatory-related diseases. In this review, we
      describe the development of chemical modification and molecular depolymerization
      methods that modify the physicochemical and biological characteristics of
      alginate. Additionally, current progress in research on immuno-inflammatory, anti
      neurodegenerative and anti-tumor activities of alginate derivatives is
      highlighted. 

PMID- 26311421
TI  - Compartmentalization of membrane trafficking, glucose transport, glycolysis,
      actin, tubulin and the proteasome in the cytoplasmic droplet/Hermes body of
      epididymal sperm.
AB  - Discovered in 1909 by Retzius and described mainly by morphology, the cytoplasmic
      droplet of sperm (renamed here the Hermes body) is conserved among all mammalian
      species but largely undefined at the molecular level. Tandem mass spectrometry of
      the isolated Hermes body from rat epididymal sperm characterized 1511 proteins,
      43 of which were localized to the structure in situ by light microscopy and two
      by quantitative electron microscopy localization. Glucose transporter 3 (GLUT-3)
      glycolytic enzymes, selected membrane traffic and cytoskeletal proteins were
      highly abundant and concentrated in the Hermes body. By electron microscope gold
      antibody labelling, the Golgi trafficking protein TMED7/p27 localized to
      unstacked flattened cisternae of the Hermes body, as did GLUT-3, the most
      abundant protein. Its biogenesis was deduced through the mapping of protein
      expression for all 43 proteins during male germ cell differentiation in the
      testis. It is at the terminal step 19 of spermiogenesis that the 43
      characteristic proteins accumulated in the nascent Hermes body. 

PMID- 26311424
TI  - The Role of Berberine in the Multi-Target Treatment of Senile Dementia.
AB  - Dementia is an acquired progressive cognitive dysfunction, affecting the content
      of consciousness rather than the level of consciousness. Most dementia is senile
      dementia, accounting for the majority of dementia. The most important and common
      form of senile dementia is refractory dementia, which includes Alzheimer's
      disease (AD) and vascular dementia (VD). Due to the diversity and uncertainty of
      the pathogenic mechanism of VD and AD, no significantly effective drug currently
      exists. Berberine is a natural isoquinoline alkaloid extracted from Coptis
      chinensis that has a wide range of pharmacological effects. studies in recent
      years have also found that berberine can additionally treat senile dementia by
      affecting neurotransmitter, anti-oxidative stress, metabolism and other multi
      target pathways. Multi-target treatment of senile dementia by berberine is a
      potential avenue of study for senile dementia treatment. 

PMID- 26311425
TI  - Neuroprotection of Coenzyme Q10 in Neurodegenerative Diseases.
AB  - Coenzyme Q10 (CoQ10) is a component of electron transport chain and acts as an
      antioxidant. It is also used for preventing neurodegeneration against
      mitochondrial deficiency and oxidative stress. Therefore, CoQ10 has received
      increasing attention as therapeutic and preventive intervention for
      neurodegenerative diseases. This review article focuses mainly on the structure
      of CoQ10, the function of CoQ10 and the relationship between mitochondrial
      impairment, oxidative stress and neurodegenerative diseases. In addition, the
      effects of CoQ10 on Alzheimer's disease, Parkinson's disease, and Huntington's
      disease are also discussed. Finally, future perspectives regarding development of
      successful treatment for neurodegenerative diseases are proposed. 

PMID- 26311427
TI  - Potential Roles of Selenium and Selenoproteins in the Prevention of Alzheimer's
      Disease.
AB  - Alzheimer's disease is a devastating and invariably fatal neurodegenerative brain
      disorder with no cure. AD is characterized by two pathological protein deposits,
      the senile plaques composed mainly of amyloid-beta (Abeta) peptide and the
      neurofibrillary tangles which are bundles of paired helical filaments (PHF) of
      protein tau. In addition, oxidative stress, disorders in signal transduction and
      metal ions dyshomeostasis also play significant roles in the development of AD. A
      large body of studies suggests that selenium (Se), either as Se-containing
      compounds or as selenoproteins, may be beneficial in reducing Alzheimer's
      pathology. Se is involved in most of the molecular pathways that are important in
      the progression of AD. We reviewed the literature regarding Se and AD and
      discussed the roles and mechanisms of Se in AD, as well as the potential of Se in
      AD prevention. 

PMID- 26311426
TI  - Relationships Between Mitochondria and Neuroinflammation: Implications for
      Alzheimer's Disease.
AB  - Mitochondrial dysfunction and neuroinflammation occur in Alzheimer's disease
      (AD). The causes of these pathologic lesions remain uncertain, but links between
      these phenomena are increasingly recognized. In this review, we discuss data that
      indicate mitochondria or mitochondrial components may contribute to
      neuroinflammation. While mitochondrial dysfunction could cause neuroinflammation,
      neuroinflammation could also cause mitochondrial dysfunction. However, based on
      the systemic nature of AD mitochondrial dysfunction as well as data from
      experiments we discuss, the former possibility is perhaps more likely. If
      correct, then manipulation of mitochondria, either directly or through
      manipulations of bioenergetic pathways, could prove effective in reducing
      metabolic dysfunction and neuroinflammation in AD patients. We also review some
      potential approaches through which such manipulations may be achieved. 

PMID- 26311428
TI  - Organoselenium Small Molecules and Chromium(III) Complexes for Intervention in
      Chronic Low-grade Inflammation and Type 2 Diabetes.
AB  - There is growing evidence to suggest that chronic, low-grade inflammation occurs
      in abdominal obesity, insulin resistance, type 2 diabetes mellitus and related
      complications, and that proinflammatory cytokines play an important role in the
      onset and progression of type 2 diabetes. These findings consequently provide new
      opportunities for the use of anti-inflammatory strategies to correct the
      metabolic disorders. Discovery of new synthetic bioactive small molecules to
      interfere with chronic, low-grade inflammation and type 2 diabetes has attracted
      considerable attention in medicinal chemistry. To date, a number of
      organoselenium small molecules and chromium(III) complexes have been shown to
      have the potential to alleviate chronic low-grade inflammation and type 2
      diabetes, including ebselen, selenomethionine, chromium picolinate, chromium
      dinicocysteinate, chromium phenylalaninate, trinuclear chromium propionate,
      chromium histidinate, chromium nicotinate, etc. Here, we review recent advances
      in development of organoselenium small molecules and chromium(III) complexes to
      intervene in chronic low-grade inflammation and type 2 diabetes, and discuss
      their mode of action, potential molecular mechanisms and toxicity. 

PMID- 26311429
TI  - The Molecular Mechanisms and Rational Design of Anti-Diabetic Vanadium Compounds.
AB  - Vanadium compounds are promising anti-diabetic agents. Although BEOV was not able
      to succeed in phase II clinical trial, great progresses have been made in the
      past three decades on the discovery and development of anti-diabetic vanadium
      compounds. A vast of knowledge has been obtained on the molecular mechanisms of
      both the pharmacological and toxicological effects of vanadium complexes. It has
      been revealed that vanadium compounds exert insulin enhancement effects and cell
      protection via a multiple mechanism involving inhibition of PTP1B, activation of
      PPARs- AMPK signaling, regulation of unfolded protein responses (UPRs), and
      stimulation of antioxidant enzymes, while vanadium-induced oxidative stress and
      inflammatory response could primarily be attributed to vanadium toxicity. Based
      on the present results concerning the relationship between structures, biological
      activities and biochemical properties, the rationale for future design of anti
      diabetic vanadium compounds has been discussed. 

PMID- 26311430
TI  - Gold(III) Complexes in the Oncological Preclinical Arena: From Aminoderivatives
      to Peptidomimetics.
AB  - In the last decade, we have been developing some gold(III) derivatives showing
      interesting antitumor properties and reduced systemic and renal toxicity,
      compared to the clinically-established reference drug cisplatin. Starting from
      the rationale at the base of our investigations, this review has been divided
      into two sections, with respect to our patented first- (aminoderivatives) and
      secondgeneration (peptidomimetics) potential drugs. Every section describes the
      in vitro and in vivo anticancer activity of the compounds, chosen as models,
      towards different types of tumor. In particular, we summarize the results
      achieved so far, in particular taking into account the latest in-depth studies
      related to their activity, mechanism of action and toxicological profile. Taken
      together, our data could open up new prospects for further advanced preclinical
      pharmacological testing. 

PMID- 26311431
TI  - Intravenous thrombolysis and intra-arterial interventions in acute ischemic
      stroke: Italian Stroke Organisation (ISO)-SPREAD guidelines.

PMID- 26311432
TI  - Small-conductance calcium-activated potassium (SK) channels in the amygdala
      mediate pain-inhibiting effects of clinically available riluzole in a rat model
      of arthritis pain.
AB  - BACKGROUND: Arthritis pain is an important healthcare issue with significant
      emotional and affective consequences. Here we focus on potentially beneficial
      effects of activating small-conductance calcium-activated potassium (SK) channels
      in the amygdala, a brain center of emotions that plays an important role in
      central pain modulation and processing. SK channels have been reported to
      regulate neuronal activity in the central amygdala (CeA, output nucleus). We
      tested the effects of riluzole, a clinically available drug for the treatment of
      amyotrophic lateral sclerosis, for the following reasons. Actions of riluzole
      include activation of SK channels. Evidence in the literature suggests that
      riluzole may have antinociceptive effects through an action in the brain but not
      the spinal cord. Mechanism and site of action of riluzole remain to be
      determined. Here we tested the hypothesis that riluzole inhibits pain behaviors
      by acting on SK channels in the CeA in an arthritis pain model. RESULTS: Systemic
      (intraperitoneal) application of riluzole (8 mg/kg) inhibited audible
      (nocifensive response) and ultrasonic (averse affective response) vocalizations
      of adult rats with arthritis (5 h postinduction of a kaolin-carrageenan
      monoarthritis in the knee) but did not affect spinal withdrawal thresholds, which
      is consistent with a supraspinal action. Stereotaxic administration of riluzole
      into the CeA by microdialysis (1 mM, concentration in the microdialysis fiber, 15
      min) also inhibited vocalizations, confirming the CeA as a site of action of
      riluzole. Stereotaxic administration of a selective SK channel blocker (apamin, 1
      uM, concentration in the microdialysis fiber, 15 min) into the CeA had no effect
      by itself but inhibited the effect of systemic riluzole on vocalizations. Off
      site administration of apamin into the basolateral amygdala (BLA) as a placement
      control or stereotaxic application of a selective blocker of large-conductance
      calcium-activated potassium (BK) channels (charybdotoxin, 1 uM, concentration in
      the microdialysis fiber, 15 min) into the CeA did not affect the inhibitory
      effects of systemically applied riluzole. CONCLUSIONS: The results suggest that
      riluzole can inhibit supraspinally organized pain behaviors in an arthritis model
      by activating SK, but not BK, channels in the amygdala (CeA but not BLA).

PMID- 26311433
TI  - A general exit strategy of monoheme cytochromes c and c2 in electron transfer
      complexes?
AB  - Using our previously reported maps of the electrostatic surface of horse heart
      ferri- and ferro-cyt c, comparisons were made between the complementary
      electrostatic surfaces of three cyt c peroxidase-cyt c complexes and the
      photosynthetic reaction center-cyt c complex, considering both iron oxidation
      states. The results obtained were consistent with a sliding mechanism for the
      electron shuttle on the surface of the protein complexes, promoted by the change
      in iron oxidation state. This mechanism was found to be in agreement with
      theoretical and NMR studies reported in the literature. Importantly, the analysis
      also provided a rationale for recognition of nonproductive associations. As we
      have previously reported the same conclusion on examination of redox partners of
      cyt c in the mitochondrial respiratory pathway, our hypothesis is that the
      proposed mechanism could represent a general exit strategy of monoheme cyts c and
      c2 in electron transfer complexes.

PMID- 26311434
TI  - Quantum walk coherences on a dynamical percolation graph.
AB  - Coherent evolution governs the behaviour of all quantum systems, but in nature it
      is often subjected to influence of a classical environment. For analysing quantum
      transport phenomena quantum walks emerge as suitable model systems. In
      particular, quantum walks on percolation structures constitute an attractive
      platform for studying open system dynamics of random media. Here, we present an
      implementation of quantum walks differing from the previous experiments by
      achieving dynamical control of the underlying graph structure. We demonstrate the
      evolution of an optical time-multiplexed quantum walk over six double steps,
      revealing the intricate interplay between the internal and external degrees of
      freedom. The observation of clear non-Markovian signatures in the coin space
      testifies the high coherence of the implementation and the extraordinary degree
      of control of all system parameters. Our work is the proof-of-principle
      experiment of a quantum walk on a dynamical percolation graph, paving the way
      towards complex simulation of quantum transport in random media. 

PMID- 26311436
TI  - Are functional traits a good predictor of global change impacts on tree species
      abundance dynamics in a subtropical forest?
AB  - Significant changes in the composition of tree species have been observed in
      various forests worldwide. We hypothesised that these changes might result from
      variable sensitivities of species to global change, and species sensitivities
      might be quantified, using functional traits. Employing long-term (1978-2010)
      species abundance data of 48 tree species from a permanent subtropical forest
      plot, where multiple global change factors have been observed, including soil
      drying, we examined the relationships between temporal trends in abundance and
      suits of functional traits. We found that species with high photosynthesis rates,
      leaf phosphorus and nitrogen concentrations, specific leaf area, hydraulic
      conductivity, turgor loss point and predawn leaf water potential had increased in
      abundance, while species with opposite trait patterns had decreased. Our results
      demonstrate that functional traits underlie tree species abundance dynamics in
      response to drought stress, thus linking traits to compositional shifts in this
      subtropical forest under global changes.

PMID- 26311435
TI  - Digoxin inhibits PDGF-BB-induced VSMC proliferation and migration through an
      increase in ILK signaling and attenuates neointima formation following carotid
      injury.
AB  - The increased proliferation and migration of vascular smooth muscle cells (VSMCs)
      are key events in the development of artery restenosis following percutaneous
      coronary intervention. Digoxin has long been used in the treatment of heart
      failure and has been shown to inhibit the proliferation of cancer cells through
      multiple pathways. However, the potential role of digoxin in the regulation of
      VSMC proliferation and migration and its effectiveness in the treatment of
      cardiovascular diseases, such as restenosis, remains unexplored. In the present
      study, we demonstrate that digoxin-induced growth inhibition is associated with
      the downregulation of CDK activation and the restoration of p27Kip1 levels in
      platelet-derived growth factor (PDGF)-stimulated VSMCs. In addition, we found
      that digoxin restored the PDGF-BB-induced inhibition of integrin linked kinase
      (ILK) expression and prevented the PDGF-BB-induced activation of glycogen
      synthase kinase (GSK)-3beta. Furthermore, digoxin inhibited adhesion molecule and
      extracellular matrix relative protein expression. Finally, we found that digoxin
      significantly inhibited neointima formation, accompanied by a decrease in cell
      proliferation following vascular injury in rats. These effects of digoxin were
      shown to be mediated, at least in part, through an increase in ILK/Akt signaling
      and a decrease in GSK-3beta signaling in PDGF-BB-stimulated VSMCs. In conclusion,
      our data demonstrate that digoxin exerts an inhibitory effect on the PDGF-BB
      induced proliferation, migration and phenotypic modulation of VSMCs, and prevents
      neointima formation in rats. These observations indicate the potential
      therapeutic application of digoxin in the treatment of cardiovascular diseases,
      such as restenosis. 

PMID- 26311437
TI  - A routine tool with far-reaching influence: Australian midwives' views on the use
      of ultrasound during pregnancy.
AB  - BACKGROUND: Ultrasound is a tool of increasing importance in maternity care.
      Midwives have a central position in the care of pregnant women. However, studies
      regarding their experiences of the use of ultrasound in this context are limited.
      The purpose of this study was to explore Australian midwives' experiences and
      views of the role of obstetric ultrasound particularly in relation to clinical
      management of complicated pregnancy, and situations where maternal and fetal
      health interests conflict. METHODS: A qualitative study was undertaken in
      Victoria, Australia in 2012, based on six focus group discussions with midwives
      (n = 37) working in antenatal and intrapartum care, as part of the CROss-Country
      Ultrasound Study (CROCUS). Data were analysed using qualitative content analysis.
      RESULTS: One overarching theme emerged from the analysis: Obstetric ultrasound--a
      routine tool with far-reaching influence, and it was built on three categories.
      First, the category'Experiencing pros and cons of ultrasound' highlighted that
      ultrasound was seen as having many advantages; however, it was also seen as
      contributing to increased medicalisation of pregnancy, to complex and sometimes
      uncertain decision-making and to parental anxiety. Second, 'Viewing ultrasound as
      a normalised and unquestioned examination' illuminated how the use of ultrasound
      has become normalised and unquestioned in health care and in wider society.
      Midwives were concerned that this impacts negatively on informed consent
      processes, and at a societal level, to threaten acceptance of human variation and
      disability. Third, 'Reflecting on the fetus as a person in relation to the
      pregnant woman' described views on that ultrasound has led to increased
      'personification' of the fetus, and that women often put fetal health interests
      ahead of their own. CONCLUSIONS: The results reflect the significant influence
      ultrasound has had in maternity care and highlights ethical and professional
      challenges that midwives face in their daily working lives concerning its use.
      Further discussion about the use of ultrasound is needed, both among health
      professionals and in the community, in order to protect women's rights to
      informed decision-making and autonomy in pregnancy and childbirth and to curb
      unnecessary medicalisation of pregnancy. Midwives' experiences and views play an
      essential role in such discussions.

PMID- 26311438
TI  - [MRI/PET for the detection of bone metastases. The new gold standard?].

PMID- 26311439
TI  - [Utility of coronal oblique slices in cervical spine MRI: Improved detection of
      the neuroforamina].
AB  - BACKGROUND AND OBJECTIVES: Angulated projections are standard in conventional
      radiography of the cervical spine, but rarely used in magnetic resonance imaging
      (MRI). As neuroforaminal pathology plays an important role in the etiology of
      radicular syndromes and may influence an operative approach, the utility of
      coronal oblique slices in MRI is explored. MATERIALS AND METHODS: In a
      retrospective setting, 25 consecutive patients with neurologically diagnosed
      cervical monoradiculopathy were identified. T2-weighted sagittal, coronal
      oblique, and transversal slice orientations were anonymized. Two radiologists and
      two neurosurgeons independently assessed the cases. Criteria were site, cause,
      and grading of the neuroforaminal stenosis and the level of confidence on a 100
      point visual analog scale (VAS). We computed interrater agreement, sensitivity,
      and t tests. RESULTS: Using only one slice orientation, the sensitivity in
      detecting the relevant neuroforamen was 0.40 for transversal, 0.68 for sagittal,
      and 0.64 for coronal oblique scans. A combination of the different angulations
      increased sensitivity and in 4 cases only the coronal oblique scans proved
      diagnostic. The readers felt significantly more confident in attributing the
      cause of the pathology on coronal oblique planes (a mean of 72 VAS points, p =
      0.0003 vs 58 (sagittal) vs 64 (transversal)). Interrater agreement was
      significantly better for experienced (kappa 0. 48) than for inexperienced readers
      (0.32, p = 0.02). CONCLUSIONS: Adding coronal oblique planes in cervical spine
      MRI increases sensitivity and confidence in attributing the cause of
      neuroforaminal pathology. They are regarded as useful by all the readers.

PMID- 26311442
TI  - Syllabic tone articulation influences the identification and use of words during
      Chinese sentence reading: Evidence from ERP and eye movement recordings.
AB  - In two experiments, we examined the contribution of articulation-specific
      features to visual word recognition during the reading of Chinese. In spoken
      Standard Chinese, a syllable with a full tone can be tone-neutralized through
      sound weakening and pitch contour change, and there are two types of two
      character compound words with respect to their articulation variation. One type
      requires articulation of a full tone for each constituent character, and the
      other requires a full- and a neutral-tone articulation for the first and second
      characters, respectively. Words of these two types with identical first
      characters were selected and embedded in sentences. Native speakers of Standard
      Chinese were recruited to read the sentences. In Experiment 1, the individual
      words of a sentence were presented serially at a fixed pace while event-related
      potentials were recorded. This resulted in less-negative N100 and anterior N250
      amplitudes and in more-negative N400 amplitudes when targets contained a neutral
      tone. Complete sentences were visible in Experiment 2, and eye movements were
      recorded while participants read. Analyses of oculomotor activity revealed
      shorter viewing durations and fewer refixations on-and fewer regressive saccades
      to-target words when their second syllable was articulated with a neutral rather
      than a full tone. Together, the results indicate that readers represent
      articulation-specific word properties, that these representations are routinely
      activated early during the silent reading of Chinese sentences, and that the
      representations are also used during later stages of word processing.

PMID- 26311443
TI  - FGF-2 Stimulates the Growth of Tenogenic Progenitor Cells to Facilitate the
      Generation of Tenomodulin-Positive Tenocytes in a Rat Rotator Cuff Healing Model.
AB  - BACKGROUND: Fibroblast growth factor (FGF)-2 has the potential to enhance tendon
      to-bone healing after rotator cuff (RC) injury. HYPOTHESIS: FGF-2 stimulates
      tenogenic differentiation of progenitors to improve the biomechanical strength
      and histological appearance of repaired RCs in rats. STUDY DESIGN: Controlled
      laboratory study. METHODS: Adult male Sprague-Dawley rats (N = 156) underwent
      unilateral surgery to repair the supraspinatus tendon to insertion sites. The FGF
      2-treated group (gelatin hydrogel containing 5 MUg of FGF-2) and a control group
      (gelatin hydrogel only) were compared to investigate the effects of FGF-2 at 2,
      4, 6, 8, and 12 weeks postoperatively. Biomechanical testing was performed at 6
      and 12 weeks. Semiquantitative histological analysis and immunohistochemical
      analysis for the proliferating cell nuclear antigen (PCNA) were performed, and
      the expression of tendon-related markers, including Scleraxis (Scx) and
      Tenomodulin (Tnmd), was monitored by real-time reverse transcription polymerase
      chain reaction (RT-PCR) and in situ hybridization. SRY-box containing gene 9
      (Sox9) expression was monitored by RT-PCR and immunohistochemical analysis. At 2
      and 4 weeks, immunohistochemical analysis for mesenchymal stem cell (MSC) markers
      was also performed. RESULTS: The FGF-2-treated group demonstrated a significant
      improvement in mechanical strength at 6 and 12 weeks and significantly higher
      histological scores than the control group at >=4 weeks. The average incidence of
      PCNA-positive cells was significantly higher at 2 and 4 weeks, and more cells
      expressing MSC markers were detected at the insertion site in the FGF-2-treated
      group. The expression level of Scx increased significantly in the FGF-2-treated
      group from 4 to 8 weeks, while the Tnmd level increased significantly from 4 to
      12 weeks postoperatively. The localization of Tnmd overlapped with the locations
      of reparative tissues accompanying collagen fibers with an aligned orientation.
      Sox9 expression was significantly upregulated at 4 weeks in the FGF-2-treated
      group. CONCLUSION: FGF-2 promotes growth of the tenogenic progenitor cells, which
      participate in tendon-to-bone healing, resulting in biomechanical and
      histological improvement of the repaired RC. CLINICAL RELEVANCE: These findings
      provide clues regarding the clinical development of regenerative repair
      strategies for RC injury.

PMID- 26311444
TI  - Why Do Osteochondral Allografts Survive? Comparative Analysis of Cartilage
      Biochemical Properties Unveils a Molecular Basis for Durability.
AB  - BACKGROUND: Transplantation of osteochondral allografts (OCAs) freshly preserved
      for >=30 days has proven to be a reliable technique for cartilage resurfacing.
      However, the prolonged storage of allografts comes at the expense of chondrocyte
      viability, which declines precipitously after 14 days under refrigeration.
      Despite this, radiographic data indicate that most allograft cartilage remains
      stable for years after implantation. The apparent durability of partially
      devitalized cartilage begs the question of how the extracellular matrix is
      maintained. HYPOTHESIS: Compared with patients' defect cartilage, replacement
      OCAs freshly preserved for 36 days on average contain significantly lower levels
      of cartilage matrix-destructive metalloproteinases, which may contribute to the
      long-term stability of implanted grafts. STUDY DESIGN: Descriptive laboratory
      study. METHODS: Chondrocyte density was determined by the cell yield from
      digested cartilage and by double-strand DNA content quantified with PicoGreen
      assay. Chondrocyte viability was estimated by staining enzymatically isolated
      chondrocytes with calcein AM and ethidium homodimer-2. Cartilage proteoglycan
      (PG) content was analyzed with dimethylmethylene blue assay. The in vitro 48-hour
      release of PG-depleting metalloproteinases including matrix metalloproteinase
      (MMP)-1, -3, -13, and ADAMTS-5 from cartilage was examined with Western blotting.
      The data were compared between diseased cartilage from patients and samples from
      matched grafts. The relative amount of MMP-3 to its endogenous inhibitor, tissue
      inhibitor of MMP-1 (TIMP-1), was also determined with Western blotting. RESULTS:
      Chondrocyte density decreased linearly with allograft storage time and declined
      by an average of 43%. PG content decreased while the percentage of nonviable
      chondrocytes increased with storage time, with the former showing less linearity.
      However, PG content remained in the normal range and was significantly higher
      than that in patients' defect cartilage. Correspondingly, significantly less PG
      depleting metalloproteinases and a much lower MMP-3/TIMP-1 ratio were detected in
      allograft cartilage than in patients' diseased cartilage. CONCLUSION: These
      findings indicated that, at the time of implantation, fresh-preserved OCAs
      contained significantly lower levels of PG-depleting metalloproteinases compared
      with patients' defect cartilage, which might contribute to their long-term
      stability in vivo. CLINICAL RELEVANCE: The comparatively low expression of
      cartilage-dissolving metalloproteinases in human OCAs freshly preserved over 30
      days offers support to the long-term durability of implanted grafts. Based on
      study data that showed similarity in the response to inflammatory cytokines
      between patients' cartilage and OCA cartilage, strategies that can alleviate
      inflammation may provide extra benefit for the survival of implanted grafts. In
      terms of the practice of graft preservation, agents that can keep balance between
      the ATP supply and demand or stabilize the cell membrane or inhibit the
      activation of metalloproteinases may significantly improve cell viability in
      fresh-preserved OCAs with a storage time longer than 5 weeks.

PMID- 26311445
TI  - Autograft Versus Allograft Anterior Cruciate Ligament Reconstruction: A
      Prospective, Randomized Clinical Study With a Minimum 10-Year Follow-up.
AB  - BACKGROUND: The use of allografts for anterior cruciate ligament (ACL)
      reconstruction in young athletes is controversial. No long-term results have been
      published comparing tibialis posterior allografts to hamstring autografts.
      PURPOSE: To evaluate the long-term results of primary ACL reconstruction using
      either an allograft or autograft. STUDY DESIGN: Randomized controlled trial;
      Level of evidence, 1. METHODS: From June 2002 to August 2003, patients with a
      symptomatic ACL-deficient knee were randomized to receive either a hamstring
      autograft or tibialis posterior allograft. All allografts were from a single
      tissue bank, aseptically processed, and fresh-frozen without terminal
      irradiation. Graft fixation was identical in all knees. All patients followed the
      same postoperative rehabilitation protocol, which was blinded to the therapists.
      Preoperative and postoperative assessments were performed via examination and/or
      telephone and Internet-based questionnaire to ascertain the functional and
      subjective status using established knee metrics. The primary outcome measures
      were graft integrity, subjective knee stability, and functional status. RESULTS:
      There were 99 patients (100 knees); 86 were men, and 95% were active-duty
      military. Both groups were similar in demographics and preoperative activity
      level. The mean and median ages of both groups were identical at 29 and 26 years,
      respectively. Concomitant meniscal and chondral pathologic abnormalities,
      microfracture, and meniscal repair performed at the time of reconstruction were
      similar in both groups. At a minimum of 10 years (range, 120-132 months) from
      surgery, 96 patients (97 knees) were contacted (2 patients were deceased, and 1
      was unable to be located). There were 4 (8.3%) autograft and 13 (26.5%) allograft
      failures that required revision reconstruction. In the remaining patients whose
      graft was intact, there was no difference in the mean Single Assessment Numeric
      Evaluation, Tegner, or International Knee Documentation Committee scores.
      CONCLUSION: At a minimum of 10 years after ACL reconstruction in a young athletic
      population, over 80% of all grafts were intact and had maintained stability.
      However, those patients who had an allograft failed at a rate over 3 times higher
      than those with an autograft.

PMID- 26311446
TI  - Baseline symptom severity predicts serotonin transporter change during
      psychotherapy in patients with major depression.
AB  - AIMS: The role of the serotonin transporter (SERT) in the pathophysiology of
      depression is unclear and only a few follow-up studies exist. Our aim was to
      measure changes in SERT availability during psychodynamic psychotherapy in
      patients with major depression over a follow-up time of 12 or 18 months. METHODS:
      The patients were studied with iodine-123 labelled 2beta-carbomethoxy-3beta-(4
      iodophenyl) serial single-photon emission tomography imaging and clinical rating
      scales of symptoms. RESULTS: Changes in SERT availability had no correlation with
      the change of symptoms, but the change of SERT availability during psychotherapy
      in the midbrain was predicted by the baseline severity of the clinical symptoms
      measured by the Symptom Checklist Depression Scale and the Symptom Checklist
      Global Severity Index. With cut-off values applied, it was found that SERT
      availabilities increased in patients with high baseline symptoms, and decreased
      in patients with low baseline symptoms. CONCLUSIONS: Together with our earlier
      finding of decreased SERT in patients with depression, these results indicate a
      state-dependent and possibly a compensatory role of decreased SERT availability
      in depression.

PMID- 26311447
TI  - Happy Birthday Albert Eschenmoser.

PMID- 26311448
TI  - [Practical guidance for termination of pregnancy at 8 to 16 weeks gestation with
      mifepristone and misoprostol].

PMID- 26311449
TI  - [Appropriate delivery mode and timing of termination for pregnancy with low birth
      weight infants].
AB  - OBJECTIVES: To investigate the delivery mode and perinatal outcomes of low birth
      weight infants in mainland China, and to explore the appropriate delivery mode
      and timing of delivery. METHODS: Clinical data of 103 678 babies delivered from
      Jan 1(st) to Dec 31(th), 2011 in 39 hospitals in mainland China were analyzed
      retrospectively. The 39 hospitals located in 7 administrative regions, including
      Northeast, Northwest, North, Central, East, South and Southwest China. RESULT:
      (1) The average birth weight of the newborns was (3 263 +/- 540) g. Among them, 7
      474 cases were diagnosed low birth weight infants, with the incidence of 7.209%
      (7 474/103 678). There were 2.328% (2 214/95 116) full-term low birth weight
      infants and 61.434% (5 260/8 562) preterm low birth weight infants. (2) From week
      28 to week 36, the cesarean section rate of low birth weight infants increased
      with the increasing of gestational weeks. The cesarean section rate of full-term
      low birth weight infants were 61.14% (1 139/1 863), which was higher than that of
      normal birth weight infants (52.947%, 45 108/85 195). The differences were
      statistically significant (P < 0.01). (3) The constitution of the indication of
      cesarean section showed that social factor and maternal factor were 10.73% (443/4
      128) and 48.91% (2 019/4 128) for low birth weight infants, respectively. While
      for the normal birth weight infants, they were 27.70% (12 495/45 108) and 38.60%
      (17 412/45 108), respectively. There was statistically significant difference (P
      < 0.01). (4) The emergency cesarean section rate of full-term low birth weight
      infants was 41.09% (468/1 139), which was higher than that of normal birth weight
      infants (31.09%, 14 024/45 108). The difference was statistically significant (P
      < 0.01). (5) The rates of stillbirth, neonatal asphyxia and the mortality of full
      term low birth weight infants were 2.36% (44/1 863), 6.12% (114/1 863), and 3.17%
      (59/1 863), respectively. Those of normal birth weight infants were 0.11% (94/85
      195), 1.41% (1 201/85 195), and 0.14% (119/85 195), respectively. The differences
      were statistically significant (P < 0.01). (6) The stillbirth rate and mortality
      of low birth weight infants born by cesarean delivery were significantly lower
      than those born by vaginal delivery. The rate of neonatal asphyxia (17.95%) and
      other morbidity (3.61%) among low birth weight infants born by cesarean section
      in week 28 to week 33(+6) were significantly lower than those born by vaginal
      delivery (30.09%, 6.62%, respectively). (7) With the increase of gestational age,
      the incidence of neonatal asphyxia and stillbirth decreased. The incidence of
      neonatal asphyxia (39.22%) and stillbirth (23.28%) was most seen in 28 to 29
      gestational weeks, which decreased to 9.08% and 2.88% in 34 gestation weeks.
      CONCLUSIONS: Low birth weight is one of the leading causes of adverse perinatal
      outcomes and cesarean section. To decrease the incidence of low birth weight,
      individualized management should be performed according to the gestational age
      and fetal condition. Extending the gestational age to at least 34 weeks may avoid
      iatrogenic preterm labor and improve the neonatal survival rate.

PMID- 26311450
TI  - [Analysis of clinical outcome and impact factors of twin-to-twin transfusion
      syndrome with anterior placenta treated by fetoscopic laser photocoagulation].
AB  - OBJECTIVE: To analyze the clinical outcome and impact factors of twin-to-twin
      transfusion syndrome (TTTS) with anterior placenta treated by fetoscopic
      selective laser coagulation of placental vessels (SLCPV). METHODS: Ten cases of
      TTTS with anterior placenta and 8 cases with posterior placenta were treated by
      SLCPV in Shengjing Hospital from July 2011 to April 2014. Clinical data were
      analyzed retrospectively. Some cases were at Quintero stage II or higher stage,
      others were at Quintero stage I but with cardiovascular score >= 5 according to
      the scoring system of Children's Hospital of Philadelphia. The anterior placenta
      cases were treated by curve fetoscopy and the posterior placenta cases were
      treated by straight fetoscopy. RESULTS: (1) Of all the 18 cases, the mean
      gestational age at SLCPV was 24.1 weeks (17(+5) to 27(+4) weeks). There were 2
      cases at Quintero stage I, 4 at stage II and 12 at stage III. The mean
      gestational age of anterior placenta cases at SLCPV was 25.2 weeks (22 to 27(+4)
      weeks), with 2 cases at Quintero stage I, 2 cases at stage II and 6 at stage III;
      5 cases had preterm prelabour rupture of the membranes (PPROM) and 1 case had
      maternal intestinal obstruction after the operation; the average operation time
      was 40 minutes. Of the posterior placenta cases, the mean gestational age at
      SLCPV was 22.7 weeks (17(+5) to 27(+4) weeks); 2 cases were at Quintero stage II
      and 6 cases at stage III. PPROM happened in one case; one case had maternal
      enterobacter cloacae septicemia; the average operation time was 28 minutes. All
      the 18 cases could tolerate the operations. There was no intraoperative
      complication. (2) One anterior placenta case had maternal intestinal obstruction
      and miscarriage; and one posterior placenta case had enterobacter cloacae
      septicemia. Karyotype analyses of the all the twins were normal. (3) 17 cases
      delivered already, including all the 10 anterior placenta cases and 7 posterior
      placenta cases. One infant had corpus callosum agenesis, but its co-twin was
      normal. The average gestational age at delivery for anterior placenta cases was
      32.6 weeks (24 to 37(+1) weeks), an was 28.2 weeks (25(+6) to 36(+2) weeks) for
      posterior placenta cases. The fetuses survival rate was 13/17 (one case was still
      in pregnancy) for at least one twin, and 10/17 for both twins. Both twins
      survival rates were 5/10, 5/7 for anterior placenta cases and posterior placenta
      cases, respectively. At least one twin survival rates were 8/10, 5/7 for the two
      groups respectively. CONCLUSION: SLCPV is suitable for the treatment of TTTS, no
      matter the placenta is on the anterior wall or posterior wall. The treatment had
      good outcomes, but more PPROM happened in the anterior placenta cases, which may
      be associated with operation time and the range of operation.

PMID- 26311451
TI  - [Maternal and fetal outcomes with aortic dissection in pregnant patients with
      Marfan syndrome].
AB  - OBJECTIVE: To evaluate the clinical characteristics of aortic dissection in
      pregnant patients with Marfan syndrome and the maternal and fetal outcomes in
      cardiovascular surgery. METHODS: Seven pregnant women with Marfan syndrome with
      aortic dissection were identified, who were treated in Beijing Anzhen Hospital
      Affiliated to Capital Medical University between January 2012 and September 2014.
      Patient charts were reviewed for cardiovascular surgery, occurrence of
      complications, clinical features and the maternal and fetal outcomes. RESULTS:
      (1) Among 7 patients, 4 cases were diagnosed as type A aortic dissection and 3
      were cases diagnosed as type B aortic dissection. The diagnosis mainly depends on
      CT angiography. New York Heart Association (NYHA) classify into 5 of level II, 1
      of level III, 1 of leveI IV. Except for 1 patient with cardiac tamponade lead to
      heart failure, the remaining 6 cases had no complications. (2) Three patients
      underwent heart surgery with cardiopulmonary bypass in second trimester and two
      patients underwent heart surgery in third trimester. Two patients terminated
      pregnancy before heart surgery (one of whom underwent artificial abortion, one of
      whom underwent cesarean section in second trimester). (3) The methods of
      cardiovascular surgeries were as follow: 3 of Bentall+Sun', 1 of Bentall+Sun'+
      right coronary artery bypass grafting, 1 of Bentall, 1 of the whole chest aorta
      replacement surgery, and 1 of femoral artery catheter chest aorta with membrane
      mesh stent implantation. The diameter of aortic roots measured during operation
      were 5 cm in 2 cases, 7 cm in 2 cases and 10 cm in 2 cases respectively. Among
      the 7 cases, 3 were conducted cesarean sections during cardiovascular surgery, 1
      was terminated pregnancy due to intrauterine fetal death after cardiovascular
      surgery, and 1 was conducted cesarean section due to severe early-onset
      preeclampsia at 30 weeks of pregnancy after cardiovascular surgery. (4) Among the
      7 cases, 3 were conducted cesarean sections during cardiovascular surgery, the
      order of which was implemented cesarean section under general anesthesia firstly
      and then operated cardiovascular surgery with cardiopulmonary bypass and
      heparinization. Two were conducted cardiovascular surgery after termination of
      pregnancy by early artificial abortion operation or hysterotomy. 1 was conducted
      Bentall surgery at 18 weeks of pregnancy, after that the patient was receiving
      warfarin until the fetal brain hemorrhage was examined by ultrasound at 31 weeks
      of pregnancy; the patient was conducted cesarean section due to intrauterine
      fetal death. 1 was conducted heart surgery at 24 weeks of pregnancy and continue
      the pregnancy to 30 weeks, was conducted cesarean section due to severe early
      onset preeclampsia at 30 weeks of pregnancy. (5) Among 7 patients, three patients
      underwent heart surgery with cardiopulmonary bypass combined with cesarean
      section. Two patients terminated pregnancy after heart surgery. Two patients
      terminated pregnancy before heart surgery. Six patients were alive and one
      patient died of multiple organ failure. (6) 3 cases of newborn with birth body
      mass between 1 080 to 1 490 g.1 case of birth died after 14 d. 2 cases for
      newborns were alive without exception. CONCLUSION: Aortic dissection poses
      serious risk for pregnant women with Marfan syndrome and the fetus, and the
      mortality rates for both the mother and the fetus are high. Early diagnosis and
      appropriate treatment should be based on maternal and fetal conditions (such as
      aortic dissection, gestational age). When fetus is mature, cardiovascular surgery
      should be carried out with cesarean section. A multi-disciplinary team between
      obstetric and cardiovascular surgery is crucial to the outcome of these critical
      patients.

PMID- 26311452
TI  - [Expression of interleukin-37 in placenta and its relationship with the
      pathogenesis of severe preeclampsia].
AB  - OBJECTIVE: To investigate the expression of interleukin-37 (IL-37) in placenta
      tissue and its relationship with the pathogenesis of severe preeclampsia.
      METHODS: All the patients were recruited in Qilu Hospital of Shangdong University
      from November 2012 to November 2013. Among them, thirty patients with severe
      preeclampsia were assigned to the preeclampsia group, and thirty-one healthy
      pregnant women were assigned to the control group. Immunohistochemistry of SP was
      used to detect the IL-37 protein expression in placenta tissue of the two groups.
      The expression level of IL-37 in placenta tissue of the two groups was detected
      by western blot. Besides, reverse transcription (RT)-PCR was used to detect the
      expression of IL-37 mRNA. The correlation between the expression of IL-37 mRNA
      and the delivery gestational age, body mass index (BMI) was analyzed. RESULTS:
      (1) IL-37 were detected in the placenta of both the preeclampsia group and the
      control group, and the expression site mainly located in the syncytiotrophoblast,
      with a small amount in cytotrophoblast. (2) The expression levels of IL-37
      protein in the preeclampsia group and the control group were 0.59 +/- 0.39 and
      0.88 +/- 0.22, respectively. The IL-37 mRNA levels in the preeclampsia group and
      the control group were 0.55 +/- 0.17 and 1.11 +/- 0.21, respectively. Both
      decreased significantly when compared to the control group (P < 0.05). (3)
      Significant correlation between the expression of IL-37 mRNA and the delivery
      gestational weeks (r = 0.209, P > 0.05) was seen neither in the preeclampsia
      group nor in the control group (r = -0.053, P > 0.05). In the severe preeclampsia
      group, the pregnant women's BMI had no significant correlation with IL-37 mRNA
      expression of placenta tissue (r = 0.102, P > 0.05), neither did the control
      group(r = -0.115, P > 0.05). CONCLUSION: IL-37 expression is significantly lower
      in severe preeclampsia placenta tissue than that in the normal pregnant women,
      which may play a protective role in the course of severe preeclampsia.

PMID- 26311453
TI  - [Impact of androgen level on body adipose tissue content and distribution in
      middle life women].
AB  - OBJECTIVE: To investigate the relationship between androgen level and body
      adipose tissue content and distribution via a cross sectional survey in healthy
      women aged 40 to 60 years. METHODS: A total of 222 women were divided into 4
      groups according menstruation status, i.e. reproductive stage, early
      perimenopausal stage, late perimenopausal stage and postmenopausal stage. Serum
      level of dehydroepiandrosterone (DHEA), total testosterone (TT) and sex hormone
      binding globulin (SHBG) were measured. Free androgen index (FAI) was calculated.
      Body adipose tissue content and distribution were measured by dual-energy X-ray
      absorptiometry. RESULTS: In women aged 40 to 60 years, DHEA, TT and FAI level of
      reproductive stage women was (12.3 +/- 4.1) nmol/L, (0.56 +/- 0.22) nmol/L and
      1.15 (quartile: 0.71 to 1.85), respectively. DHEA, TT and FAI level of early
      perimenopausal stage women was (12.0 +/- 3.4) nmol/L, (0.56 +/- 0.24) nmol/L and
      1.37 (quartile: 0.89 to 1.61), respectively. DHEA, TT and FAI level of late
      perimenopausal stage women was (14.2 +/- 4.7) nmol/L, (0.62 +/- 0.18) nmol/L and
      1.38 (quartile: 1.12 to 1.63). DHEA, TT and FAI level of postmenopausal stage
      women was (11.6 +/- 3.5) nmol/L, (0.45 +/- 0.22) nmol/L and 0.94 (quartile: 0.47
      to 1.49). DHEA, TT and FAI level of perimenopausal stage women was comparable
      with those of reproductive stage women (P > 0.05), however, TT and FAI level of
      postmenopausal women was significantly lower than those of reproductive stage
      women (P = 0.001, 0.014). The total adipose percentage of reproductive stage
      women, early perimenopausal stage women, late perimenopausal stage women and
      postmenopausal stage women were (35 +/- 6)%, (35 +/- 5)%, (37 +/- 4)% and (37 +/-
      5)%. The adipose percentage in "android" area of reproductive stage women, early
      perimenopausal stage women, late perimenopausal stage women and postmenopausal
      stage women were (43 +/- 5)%, (43 +/- 4)%, (47 +/- 5)% and (46 +/- 5)%. The total
      adipose percentage was similar in 4 groups (P = 0.312). Compared with
      reproductive stage women, adipose percentage of "android" area increased in late
      perimenopausal and postmenopausal women (P = 0.026). Women with higher FAI level
      presented higher adipose tissue content and higher percentage of centrally
      distributed adipose tissue (r = 0.28, P = 0.003). CONCLUSIONS: Body adipose
      tissue tends to distribute centrally from perimenopausal stage. Androgen level is
      related to body adipose tissue content and distribution, but may not be the main
      reason of changes of fat distribution in middle life women.

PMID- 26311454
TI  - [Clinical study of anti-Mullerian hormone in prediction of ovarian aging].
AB  - OBJECTIVE: To explore the serum anti-Mullerian hormone (AMH) level in women of
      childbearing age with normal menstrual cycles. METHODS: A total of 1 423 women
      with regular menstrual cycles were selected and divided into 5 groups according
      to their ages, i.e. <= 25, 26-30, 31-35, 36-40, >= 41 years. Their serum levels
      of AMH were measured, and the relationship between AMH and age was analyzed.
      RESULTS: The serum AMH levels of 5 groups according to ages (<= 25, 26-30, 31-35,
      36-40, >= 41 years) were 3.62, 3.10, 2.27, 1.07, 0.45 ug/L, respectively. The
      comparison of serum AMH levels in different age groups had significant difference
      (P < 0.01). Serum AMH level declined with increasing age, and dropped
      significantly after 36. The serum AMH level and age showed a negative correlation
      with significant difference (r = -0.374, P < 0.01). Quadratic regression of
      logAMH proximally reflected the relationship between AMH and age. CONCLUSION: AMH
      determination for women of childbearing age could provide reference for the
      evaluation of ovarian function.

PMID- 26311455
TI  - [Investigation of the change of adiponectin level with menopause status in middle
      aged women and its relationship with androgen].
AB  - OBJECTIVE: To investigate the change of adiponectin level with menopause status
      in women aged 40 to 65, and its relationship with androgen. METHODS: A cross
      sectional study included woman (aged from 40 to 65) who were in hospital for
      routine check-up at the Sun Yat-sen Memorial Hospital from August to October in
      2013. All subjects underwent laboratory examinations of adiponectin, sex hormone
      binding globulin (SHBG), dehydroepiandrosterone-sulfate (DHEA-S), total
      testosterone (TT), collected anthropometric measurements and then calculated free
      androgen index (FAI) and body mass index (BMI). According to their menstrual
      status, the subjects were divided into 4 groups: premenopausal group with 119
      subjects, perimenopausal group with 60 subjects, early postmenopausal group with
      62 subjects, late postmenopausal group with 64 subjects. RESULTS: (1) Adiponectin
      levels declined to its lowest level in menopausal transition and gradually
      becoming higher after menopause, which showed a U-shaped trajectory. When
      compared adiponectin levels in late postmenopausal group [(13 +/- 5) mg/L] with
      those in perimenopausal [(8 +/- 6) mg/L] or early postmenopausal group [(9 +/- 6)
      mg/L], it all showed significantly difference (P < 0.05). (2) Both the
      adiponectin levels were negatively correlated with waistline in the 4 groups
      (premenopausal group, r = -0.276; perimenopausal group, r = -0.334; early
      postmenopausal group, r = -0.211; late postmenopausal group, r = -0.218; all P <
      0.05). Levels of adiponectin were positively correlated with SHBG (r = 0.536, P <
      0.05) and negatively with FAI (r = -0.363, P < 0.05) in menopausal transition,
      while in late postmenopausal group, negatively correlated with level of DHEA-S (r
      = -0.450, P < 0.05). When adjusted for age, BMI and waistline, the above
      correlations still exist. CONCLUSIONS: Adiponectin levels declined to its lowest
      level in menopausal transition and gradually becoming higher after menopause,
      which showed a U-shaped trajectory during the sequential menopause status
      transition in middle aged women. Low level of adiponectin in menopausal
      transition is closely associated with the relative excess androgen occurred
      during this stage.

PMID- 26311456
TI  - [Agreement between colposcopic diagnosis with 2011 international terminology of
      colposcopy and cervical pathology in cervical lesions].
AB  - OBJECTIVE: To evaluate the agreement between colposcopic diagnosis with 2011
      colposcopic terminology of the International Federation for Cervical Pathology
      and Colposcopy (IFCPC) and cervical pathology in cervical lesions. METHODS: A
      retrospective cohort study was performed, which included 376 patients who
      underwent colposcopy with 2011 international terminology of colposcopy at
      Obstetrics and Gynecology Hospital of Fudan University from September 2014 to
      November 2014. With conization or cervical biopsy pathology as the gold standard,
      the agreement between colposcopic diagnosis and pathologic diagnosis was
      calculated and correlations between variables were analyzed. RESULTS: With 2011
      international terminology of colposcopy, agreement of colposcopic diagnosis and
      cervical pathology was 60.9% (229/376) perfectly matched, and the strength of
      agreement with weighted Kappa statistic was 0.401 (P < 0.01), and agreement
      within one grade was 97.6% (367/376), which were improved compared with
      traditional methods. Colposcopic diagnosis were 19.9% (75/376) overestimated and
      19.1% (72/376) underestimated. There were no significant difference between
      agreements in various grade lesions (chi(2) = 1.996, P = 0.573). Positive
      predictive value of high grade colposcopy or more was 84.4%, the negative
      predictive value of low grade colposcopy or less was 88.8%, whereas false
      positives were 3.5% and false negatives were 39.3%. A linear trend among three
      types of transformation zone and patient ages was found (chi(2) = 45.910, P <
      0.01), whereas lesion sizes were not linearly correlated with lesion degrees
      (chi(2) = 0.690, P = 0.406). In grade 1, grade 2 and nonspecific findings, thin
      acetowhite epithelium, dense acetowhite epithelium and Lugol's non-staining were
      most frequent, the Youden indexes of each were 0.170, 0.373 and 0.145, 0.069
      respectively. Positive predictive value of some other findings (such as fine
      mosaic) and two new signs (inner border sign and ridge sign) were 100.0%. There
      were no significant difference between agreements in examiners with different
      levels of experience (chi(2) = 1.197, P = 0.550). CONCLUSIONS: Compared to
      traditional methods (such as Reid index), 2011 international terminology of
      colposcopy could improve the agreement between colposcopic diagnosis and
      pathologic diagnosis, without significant differences by the severity of lesion
      and the level of examiners' experience. Common findings were classified
      reasonably, and some signs were highly reliable, which is important for guiding
      biopsy. However, the reproducibility of transformation zone types and the
      implication of lesion size need to be further discussed.

PMID- 26311457
TI  - [Production and mechanism of CCL5 by macrophages in U14 cervical cancer-bearing
      mice during infection].
AB  - OBJECTIVE: To investigate the production and mechanism of chemokine (C-C motif)
      ligand 5 (CCL5) by macrophages in U14 cervical cancer-bearing mice during
      infection. METHODS: The U14 cervical cancer cells were injected in C57BL/6 mice
      to induce tumor-bearing condition. Lipopolysaccharide (LPS) was injected into
      C57BL/6 mice to induce infection. The protein expression of CCL5 in the serum and
      the CCL5 mRNA expression in inflammatory cells were measured by ELISA and
      fluorescence quantitative-PCR in four groups. Macrophages were induced in the
      tumor conditioned medium (TCM) which extracted from mice serum. The protein
      expression levels of CCL5, prostaglandin E2 (PGE2) and cyclic adenosine
      monophosphate (cAMP) in the medium and CCL5, PGE2 and cAMP mRNA expression in the
      macrophages were detected in different groups. In order to determine whether the
      inhibition was related to PGE2, selective cyclooxygenase 2(COX-2) inhibitor NS398
      was used to reverse this phenomenon and protein kinase A (PKA) inhibitor H89
      demonstrated the mechanism through blocking cAMP/PKA signaling pathway. RESULTS:
      (1) The protein and mRNA level of CCL5 in tumor-bearing mice were respectively
      (151 +/- 35) pg/ml and 1.0, which were lower than those in the tumor-free mice
      (691 +/- 85) pg/ml and 4.5 +/- 0.8, there were significant difference between
      them (all P < 0.05). The protein and mRNA level of PGE2 in tumor-bearing mice
      were (1 198 +/- 83) pg/ml and 5.8 +/- 0.8, which were higher than those in the
      tumor-free mice (187 +/- 25) pg/ml and 1.0, the difference were significant (all
      P < 0.05). The protein and mRNA level of CCL5 in tumor-free + LPS mice were (4
      049 +/- 141) pg/ml and 31.5 +/- 2.0, which were higher than those in the tumor
      bearing + LPS mice (1 951 +/- 71) pg/ml and 12.1 +/- 2.8, the difference were
      also significant (P < 0.05). The protein and mRNA level of PGE2 in tumor-free +
      LPS mice were (676 +/- 70) pg/ml and 3.4 +/- 0.4, which were lower than those in
      tumor-bearing + LPS mice (2 550 +/- 382) pg/ml and 11.6 +/- 0.9, the difference
      were also significant (all P < 0.05). (2) Macrophages were cultured in vitro
      using TCM derived from mice. The protein and mRNA level of CCL5 in tumor-bearing
      mice TCM were respectively (1 626 +/- 177) pg/ml and 28.6 +/- 1.2, which were
      higher than those in the tumor-free mice TCM [(27 +/- 3) pg/ml and 1.0], there
      were significant difference (P < 0.05). The protein and mRNA level of PGE2 in
      tumor-bearing mice TCM were (790 +/- 156) pg/ml and 1.7 +/- 0.3, which were
      higher than those in the tumor-free mice TCM [(448 +/- 115) pg/ml, 1.0], the
      difference were significant (all P < 0.05). The protein and mRNA level of cAMP in
      tumor-bearing mice TCM were (164 +/- 30) pg/ml and 1.6 +/- 0.3, which weres
      higher than those in the tumor-free mice TCM [(118 +/- 25) pg/ml,1.0], the
      difference were significant (all P < 0.05). The protein and mRNA level of CCL5 in
      tumor-free + LPS mice TCM were (10 475 +/- 742) pg/ml and 212.0 +/- 5.7, which
      were higher than those in the tumor-bearing + LPS mice TCM [(6 375 +/- 530)
      pg/ml, 142.3 +/- 2.5], the difference were significant (all P < 0.05). The
      protein and mRNA level of PGE2 in tumor-free + LPS mice TCM were (2 438 +/- 95)
      pg/ml and 4.3 +/- 0.7, which weres lower than those in the tumor-bearing + LPS
      mice TCM [(3 441 +/- 163) pg/ml, 5.9 +/- 0.3], the difference were significant
      (all P < 0.05). The protein and mRNA level of cAMP in tumor-free + LPS mice TCM
      were (340 +/- 13) pg/ml and 4.1 +/- 0.4, which were lower than those in the tumor
      bearing + LPS mice TCM [(542 +/- 42) pg/ml, 5.4 +/- 0.5], the difference were
      significant (all P < 0.05). (3) Using COX-2 inhibitor NS398 in the tumor-bearing
      + LPS mice, the protein and mRNA level of CCL5, PGE2 and cAMP were (7 691 +/-
      269) pg/ml and 159.0 +/- 8.9, (2 820 +/- 152) pg/ml and 4.9 +/- 0.3, (465 +/- 8)
      pg/ml and 4.3 +/- 0.4, respectively, and there were significant difference (all P
      < 0.05), compared to before treatment. Using PKA inhibitor H89 in the tumor
      bearing + LPS mice, the protein and mRNA level of CCL5, PGE2 and cAMP were (8 375
      +/- 520) pg/ml and 177.0 +/- 8.8, (2 650 +/- 35) pg/ml and 4.7 +/- 0.4, (368 +/-
      13) pg/ml and 3.1 +/- 0.7, respectively, and there were significant difference
      (all P < 0.05), compared to before treatment. CONCLUSION: TCM of U14 cells
      activated macrophages to release PGE2 could inhibit the expression of CCL5 levels
      by cAMP/PKA signaling pathway.

PMID- 26311458
TI  - Bubble CPAP for pneumonia: perils of stopping trials early.

PMID- 26311459
TI  - The Polycystin-1, Lipoxygenase, and alpha-Toxin Domain Regulates Polycystin-1
      Trafficking.
AB  - Mutations in polycystin-1 (PC1) give rise to autosomal dominant polycystic kidney
      disease, an important and common cause of kidney failure. Despite its medical
      importance, the function of PC1 remains poorly understood. Here, we investigated
      the role of the intracellular polycystin-1, lipoxygenase, and alpha-toxin (PLAT)
      signature domain of PC1 using nuclear magnetic resonance, biochemical, cellular,
      and in vivo functional approaches. We found that the PLAT domain targets PC1 to
      the plasma membrane in polarized epithelial cells by a mechanism involving the
      selective binding of the PLAT domain to phosphatidylserine and L-alpha
      phosphatidylinositol-4-phosphate (PI4P) enriched in the plasma membrane. This
      process is regulated by protein kinase A phosphorylation of the PLAT domain,
      which reduces PI4P binding and recruits beta-arrestins and the clathrin adaptor
      AP2 to trigger PC1 internalization. Our results reveal a physiological role for
      the PC1-PLAT domain in renal epithelial cells and suggest that phosphorylation
      dependent internalization of PC1 is closely linked to its function in renal
      development and homeostasis.

PMID- 26311461
TI  - Confluentimicrobium naphthalenivorans sp. nov., a naphthalene-degrading bacterium
      isolated from sea-tidal-flat sediment, and emended description of the genus
      Confluentimicrobium Park et al. 2015.
AB  - A Gram-staining-negative, aerobic and moderately halophilic bacterium, designated
      strain NS6T, was isolated from sea-tidal-flat sediment of the South Sea in Korea.
      Cells were motile rods with a single flagellum showing positive catalase and
      oxidase activities. Strain NS6T grew at 15-40  degrees C (optimum, 30  degrees
      C), at pH 6.0-9.0 (optimum, pH 7.0-7.5) and in the presence of 1-5 % (w/v) NaCl
      (optimum, 2 %). Ubiquinone-10 was identified as the only isoprenoid quinone and
      summed feature 8 (comprising C18 : 1omega7c/omega6c), C19 : 0 cyclo omega8c, C16
      : 0 and C10 : 0 3-OH were the major fatty acids. Strain NS6T contained
      phosphatidylglycerol, sulfoquinovosyldiacylglycerol, an unidentified amino lipid
      and an unidentified lipid as the major polar lipids. An unidentified phospholipid
      and three unidentified lipids were also detected as the minor polar lipids. The
      G+C content of the genomic DNA was 64.5 mol%. Strain NS6T was most closely
      related to Confluentimicrobium lipolyticum SSK1-4T with a 96.8 % 16S rRNA gene
      sequence similarity, and the phylogenetic analysis based on 16S rRNA gene
      sequences showed that strain NS6T formed a tight phylogenetic lineage with C.
      lipolyticum SSK1-4T. The physiological, chemotaxonomic and phylogenetic
      properties suggest that strain NS6T represents a novel species of the genus
      Confluentimicrobium, for which the name Confluentimicrobium naphthalenivorans sp.
      nov. is proposed. The type strain is NS6T ( = KCTC 18418T = JCM 30828T). An
      emended description of the genus Confluentimicrobium is also proposed.

PMID- 26311462
TI  - Risk Factors for Postoperative Infections After Dental Implant Placement: A Case
      Control Study.
AB  - PURPOSE: To determine possible risk factors for postoperative infections after
      implant surgery, explain their effects on the occurrence of such infections, and
      assess the relation between postoperative infections and early implant failure.
      PATIENTS AND METHODS: A case-and-control study was performed. Postoperative
      infections were defined as purulent drainage or fistula in the operated region
      with pain or tenderness, localized swelling, redness, and heat or fever before
      prosthetic loading. Bivariate and multivariate analyses of the data were
      performed. RESULTS: Eighty-eight outpatients (22 patients in the infection group
      and 66 controls) were selected. Male gender and submerged healing were
      meaningfully associated to the development of postoperative infections (bivariate
      analysis). Healing type and location were the independent variables included in
      the final logistic regression model. Postoperative infections during the
      osseointegration period considerably increased the risk of early failure (odds
      ratio = 78.0; 95% confidence interval, 9.12 to 666.90). CONCLUSIONS: Patients
      undergoing dental implant placement in the mandible with submerged healing are
      more prone to postoperative infections. This complication is relevant because it
      is associated with a considerable and almost 80-fold increase in the risk of
      early implant failure.

PMID- 26311460
TI  - Uremic Toxicity of Advanced Glycation End Products in CKD.
AB  - Advanced glycation end products (AGEs), a heterogeneous group of compounds formed
      by nonenzymatic glycation reactions between reducing sugars and amino acids,
      lipids, or DNA, are formed not only in the presence of hyperglycemia, but also in
      diseases associated with high levels of oxidative stress, such as CKD. In chronic
      renal failure, higher circulating AGE levels result from increased formation and
      decreased renal clearance. Interactions between AGEs and their receptors,
      including advanced glycation end product-specific receptor (RAGE), trigger
      various intracellular events, such as oxidative stress and inflammation, leading
      to cardiovascular complications. Although patients with CKD have a higher burden
      of cardiovascular disease, the relationship between AGEs and cardiovascular
      disease in patients with CKD is not fully characterized. In this paper, we review
      the various deleterious effects of AGEs in CKD that lead to cardiovascular
      complications and the role of these AGEs in diabetic nephropathy. We also discuss
      potential pharmacologic approaches to circumvent these deleterious effects by
      reducing exogenous and endogenous sources of AGEs, increasing the breakdown of
      existing AGEs, or inhibiting AGE-induced inflammation. Finally, we speculate on
      preventive and therapeutic strategies that focus on the AGE-RAGE axis to prevent
      vascular complications in patients with CKD. 

PMID- 26311463
TI  - Resuscitation of a dead cardiomyocyte.
AB  - Although cardiac resuscitation can revive the whole body, the mechanisms are
      unclear. To this end, we propose that reviving a dead/dysfunctional cardiomyocyte
      will shed light on resuscitation mechanisms and pave the way to treat cardiac
      myopathies. The degradation of the myocyte cytoskeleton by the proteasome system
      which involves calpains, ubiquitin, caspases and matrix metalloproteases is the
      main focus of this review. The activation of calpains beyond the calpastatin
      mediated inhibition due to extensive calcium harbor can lead to titin
      degradation, damage to the sarcomere and contractile dysfunction. The ubiquitin
      proteasome system can disturb the protein homeostasis within the cell and
      generate a dysfunctional myocyte. The matrix metalloproteases disrupt the
      collagen/elastin ratio and connexins to generate arrhythmias. The concept of
      cardiac resuscitation stems from protecting the myocyte cytoskeleton and keeping
      the protein homeostasis intact through management of the degradation machinery.
      In this regard, proteasome inhibitors for the degradation machinery have an
      elegant space. Recently exosomes have been identified potentially, as carriers of
      microRNAs or proteins that can modify the target cells. Exosomes loaded with the
      inhibitor "cargo" which comprises microRNAs, siRNAs or proteins to inhibit the
      degradation machinery can be a method of choice for cardiac resuscitation-a
      process difficult to execute. 

PMID- 26311464
TI  - Iminoboronate Formation Leads to Fast and Reversible Conjugation Chemistry of
      alpha-Nucleophiles at Neutral pH.
AB  - Bioorthogonal reactions that are fast and reversible under physiological
      conditions are in high demand for biological applications. Herein, it is shown
      that an ortho boronic acid substituent makes aryl ketones rapidly conjugate with
      alpha-nucleophiles at neutral pH. Specifically, 2-acetylphenylboronic acid and
      derivatives were found to conjugate with phenylhydrazine with rate constants of
      10(2) to 10(3) M(-1) s(-1) , comparable to the fastest bioorthogonal conjugations
      known to date. (11) B NMR analysis revealed the varied extent of iminoboronate
      formation of the conjugates, in which the imine nitrogen forms a dative bond with
      boron. The iminoboronate formation activates the imines for hydrolysis and
      exchange, rendering these oxime/hydrazone conjugations reversible and dynamic
      under physiological conditions. The fast and dynamic nature of the iminoboronate
      chemistry should find wide applications in biology.

PMID- 26311465
TI  - Anhedonia in pigs? Effects of social stress and restraint stress on sucrose
      preference.
AB  - The fact that consumption of normally palatable foods is affected by stress in
      both humans and rats suggests a means to assess hedonic reaction in non-verbal
      animals. However, little is known about anhedonia and stress in productive
      animals such as pigs. Thus we examined the separate effects of social stress and
      restraint stress in 42-day old pigs on the preference for dilute sucrose
      solutions over water. Pigs in the social stress group (SS) were mixed with
      unfamiliar animals from separate pens for two 20 minute periods (Experiment 1).
      Pigs in the restraint stress group (RS) were immobilized three times a day, for 3
      min periods, on 3 consecutive days (Experiment 2). Consumption of dilute sucrose
      solutions and water was examined after these stress manipulations and in the
      unstressed control groups (CG). Pigs were tested in pairs (12 control and 12
      experimental) with a choice between water and sucrose solutions (at either 0.5%
      or 1%) during 30 min sessions. In both experiments CG pigs showed higher intakes
      of 0.5% and 1% sucrose solutions over water. Neither SS nor RS pigs consumed more
      0.5% sucrose than water, but both groups did consume more 1% sucrose than water.
      Both social stress and restraint stress reduced sucrose preference at low
      concentrations but not at higher concentrations suggesting that stress may limit
      food consumption in pigs unless a palatable feed is present. In addition, the
      results suggest that stress reduces the hedonic impact of dilute sucrose.
      Therefore, sucrose preference may be a useful test for the presence of stress and
      anhedonia in pigs.

PMID- 26311467
TI  - The role of objects and effects in action imitation: Comparing the imitation of
      object-related actions vs. gestures in 18-month-old infants.
AB  - This study aimed to systematically investigate 18-month-old infants' imitation of
      object-related actions compared to motorically similar gestures. An additional
      goal of the study was to examine the role of action effects on infants' imitation
      of target actions. One group of infants (n=17) observed object-related actions
      and gestures leading to salient effects (sounds or visual resp. social effects),
      and the other group (n=16) watched the same actions without effects. Furthermore,
      this study examined whether infants show a consistent imitation ability for
      object-related actions and gestures. First, the present study showed that 18
      month-old infants imitated object-related actions more frequently than gestures.
      Second, the presence of an effect significantly increased the imitation rate of
      object-related actions; however, this difference was not found for gestures.
      Third, indications for a general imitation ability were found as results on an
      individual level showed that object-related action imitation significantly
      correlated with gesture imitation. Implications of the results for theory and
      future studies are discussed with a focus on the role of objects and effects in
      18-month-old infants' action imitation. 

PMID- 26311466
TI  - Fgf15 regulates thalamic development by controlling the expression of proneural
      genes.
AB  - The establishment of the brain structural complexity requires a precisely
      orchestrated interplay between extrinsic and intrinsic signals modulating
      cellular mechanisms to guide neuronal differentiation. However, little is known
      about the nature of these signals in the diencephalon, a complex brain region
      that processes and relays sensory and motor information to and from the cerebral
      cortex and subcortical structures. Morphogenetic signals from brain organizers
      regulate histogenetic processes such as cellular proliferation, migration, and
      differentiation. Sonic hedgehog (Shh) in the key signal of the ZLI, identified as
      the diencephalic organizer. Fgf15, the mouse gene orthologous of human, chick,
      and zebrafish Fgf19, is induced by Shh signal and expressed in the diencephalic
      alar plate progenitors during histogenetic developmental stages. This work
      investigates the role of Fgf15 signal in diencephalic development. In the absence
      of Fgf15, the complementary expression pattern of proneural genes: Ascl1 and
      Nng2, is disrupted and the GABAergic thalamic cells do not differentiate; in
      addition dorsal thalamic progenitors failed to exit from the mitotic cycle and to
      differentiate into neurons. Therefore, our findings indicate that Fgf15 is the
      Shh downstream signal to control thalamic regionalization, neurogenesis, and
      neuronal differentiation by regulating the expression and mutual segregation of
      neurogenic and proneural regulatory genes.

PMID- 26311468
TI  - Maternal depression and the learning-promoting effects of infant-directed speech:
      Roles of maternal sensitivity, depression diagnosis, and speech acoustic cues.
AB  - The hypothesis that the associative learning-promoting effects of infant-directed
      speech (IDS) depend on infants' social experience was tested in a conditioned
      attention paradigm with a cumulative sample of 4- to 14-month-old infants.
      Following six forward pairings of a brief IDS segment and a photographic slide of
      a smiling female face, infants of clinically depressed mothers exhibited evidence
      of having acquired significantly weaker voice-face associations than infants of
      non-depressed mothers. Regression analyses revealed that maternal depression was
      significantly related to infant learning even after demographic correlates of
      depression, antidepressant medication use, and extent of pitch modulation in
      maternal IDS had been taken into account. However, after maternal depression had
      been accounted for, maternal emotional availability, coded by blind raters from
      separate play interactions, accounted for significant further increments in the
      proportion of variance accounted for in infant learning scores. Both maternal
      depression and maternal insensitivity negatively, and additively, predicted poor
      learning. 

PMID- 26311469
TI  - Maturational and situational determinants of reaching at its onset.
AB  - At 3 months of age, reaching behavior was measured in a group of 10 girls and 10
      boys born at term. The assessments were carried out on the average 2 days after
      reaching onset. Reaching kinematics was measured in both supine and reclined
      positions. Girls reached more than boys, had straighter reaching trajectories and
      movements of shorter durations as well as fewer movement units. The reclined
      position gave rise to straighter trajectories in both girls and boys. Several
      anthropometric parameters were measured. Girls had less length and volume of the
      forearm than boys but similar upper arm volumes. There was a weak relation
      between kinematic and anthropometric variables. 

PMID- 26311471
TI  - Novel agents for castration-resistant prostate cancer: Early experience and
      beyond.
AB  - Androgen deprivation therapy is the initial treatment for men with advanced
      prostate cancer. Almost all these patients eventually develop progressive
      castration-resistant prostate cancer despite an initial favorable response.
      Docetaxel was the first agent to show a survival benefit in patients with
      castration-resistant prostate cancer. After cancer progression on docetaxel,
      patients with castration-resistant prostate cancer had few therapeutic options. A
      better understanding of the mechanisms of resistance to androgen deprivation
      therapy has led to the development of novel agents with distinct mechanisms of
      action. Prospective, large-scale clinical trials have shown overall survival
      benefits with the hormonal agents abiraterone acetate and enzalutamide, the
      immunotherapeutic agent sipuleucel T, the chemotherapeutic agent cabazitaxel, and
      bone-targeted Ra-223. Although these agents provided clinical benefit, treatment
      for castration-resistant prostate cancer remains a major clinical challenge. We
      recognize many questions, such as methods to select patients for specific
      treatments, optimal sequencing and drug combinations, and means to overcome drug
      resistance. There is an urgent need to answer these questions and to establish
      better treatment strategies. The development of biomarkers that are predictive of
      treatment results is also required. The present article reviews new castration
      resistant prostate cancer treatments, and discusses possible resistant mechanisms
      as well as potential drug combinations and optimal sequencing.

PMID- 26311470
TI  - RNAseq analysis of Aspergillus fumigatus in blood reveals a just wait and see
      resting stage behavior.
AB  - BACKGROUND: Invasive aspergillosis is started after germination of Aspergillus
      fumigatus conidia that are inhaled by susceptible individuals. Fungal hyphae can
      grow in the lung through the epithelial tissue and disseminate hematogenously to
      invade into other organs. Low fungaemia indicates that fungal elements do not
      reside in the bloodstream for long. RESULTS: We analyzed whether blood represents
      a hostile environment to which the physiology of A. fumigatus has to adapt. An in
      vitro model of A. fumigatus infection was established by incubating mycelium in
      blood. Our model allowed to discern the changes of the gene expression profile of
      A. fumigatus at various stages of the infection. The majority of described
      virulence factors that are connected to pulmonary infections appeared not to be
      activated during the blood phase. Three active processes were identified that
      presumably help the fungus to survive the blood environment in an advanced phase
      of the infection: iron homeostasis, secondary metabolism, and the formation of
      detoxifying enzymes. CONCLUSIONS: We propose that A. fumigatus is hardly able to
      propagate in blood. After an early stage of sensing the environment, virtually
      all uptake mechanisms and energy-consuming metabolic pathways are shut-down. The
      fungus appears to adapt by trans-differentiation into a resting mycelial stage.
      This might reflect the harsh conditions in blood where A. fumigatus cannot take
      up sufficient nutrients to establish self-defense mechanisms combined with
      significant growth.

PMID- 26311472
TI  - Metabolites identification of bioactive licorice compounds in rats.
AB  - Licorice (Glycyrrhiza uralensis Fisch.) is one of the most popular herbal
      medicines worldwide. This study aims to identify the metabolites of seven
      representative bioactive licorice compounds in rats. These compounds include
      22beta-acetoxyl glycyrrhizin (1), licoflavonol (2), licoricidin (3),
      licoisoflavanone (4), isoglycycoumarin (5), semilicoisoflavone B (6), and 3
      methoxy-9-hydroxy-pterocarpan (7). After oral administration of 250mg/kg of 1 or
      40mg/kg of 2-7 to rats, a total of 16, 43 and 31 metabolites were detected in the
      plasma, urine and fecal samples, respectively. The metabolites were characterized
      by HPLC/DAD/ESI-MS(n) and LC/IT-TOF-MS analyses. Particularly, two metabolites of
      1 were unambiguously identified by comparing with reference standards, and 22beta
      acetoxyl glycyrrhizin-6"-methyl ester (1-M2) is a new compound. Compound 1 could
      be readily hydrolyzed to eliminate the glucuronic acid residue. The phenolic
      compounds (4-7) mainly undertook phase II metabolism (glucuronidation or
      sulfation). Most phenolic compounds with an isoprenyl group (chain or cyclized, 2
      5) could also undertake hydroxylation reaction. This is the first study on in
      vivo metabolism of these licorice compounds.

PMID- 26311473
TI  - Determination of designer doping agent--2-ethylamino-1-phenylbutane--in dietary
      supplements and excretion study following single oral supplement dose.
AB  - The quantitative analysis of a new designer doping agent, 2-ethylamino-1
      phenylbutane (EAPB) and its metabolite, 2-amino-1-phenylbutane (APB) in urine
      samples, and the determination of EAPB in dietary supplement samples, have been
      presented. The main purpose of the present study was to develop simple and
      reliable gas chromatography-mass spectrometry method (GC-MS) for excretion study
      following a single oral administration of dietary supplements containing EAPB.
      Three analytical methods for the determination of EAPB in urine and supplement
      samples, and APB in urine samples using the GC-MS system, have been validated.
      The method of the determination of EAPB in supplement samples was applied to
      analyze seventeen dietary supplements, CRAZE and DETONATE. Two other methods were
      used to determine the urinary excretion profile of EAPB and APB in the case of
      three healthy volunteers and, on further investigation, it was applied to the
      anti-doping control in sport. Quantification was obtained on the basis of the
      ions at m/z 86, 58 and 169, monitored for EAPB, APB and diphenylamine (used as an
      internal standard), respectively. The limits of detection and quantification were
      2.4 and 7.3MUg/g for EAPB in the case of supplement analysis, 2.9 and 8.8ng/mL
      for EAPB in the case of urine analysis, and 3.2 and 9.7ng/mL for APB. The other
      validation parameters as linearity, precision and trueness have been also
      investigated with the acceptable results. The extraction yield of all presented
      methods was above 69%. EAPB was detected in fourteen analyzed supplements (not
      included EAPB in their labels) and its content varied between 1.8 and 16.1mg/g.
      Following oral administration of three supplements with EAPB to one male and two
      female volunteers, the parent compound of EAPB and its metabolite were monitored
      and the excretion parameters as the maximum concentration of the analyte in urine
      (2.2-4.2MUg/mL for EAPB; 1.1-5.1MUg/mL for APB) and the time for the maximum
      height of the excretion peak (2-8h and 22h in one case for EAPB; 20-22h and 4h in
      one case for APB) have been indicated. EAPB and APB were detected at the level
      above 50ng/mL (50% of the minimum required performance level for stimulants in
      the anti-doping control in-competition in sport) in the urine up to 46-106h and
      58-120h, respectively. Additionally, the result of the anti-doping control during
      swimming competition of one athlete, whose urine sample was analyzed for
      stimulants and narcotics, has been presented. The qualitative and quantitative
      analyses of new designer agents in urine samples and the excretion studies of
      these substances are of a great importance in the anti-doping control in sport.
      Moreover, the presentation of detection examples of these agents in supplements
      that haven't got included an information about them in the labeling, make
      athletes (and other supplement customers) more and more aware of the risk of the
      supplement use and possible health and doping consequences.

PMID- 26311474
TI  - Inference Under a Wright-Fisher Model Using an Accurate Beta Approximation.
AB  - The large amount and high quality of genomic data available today enable, in
      principle, accurate inference of evolutionary histories of observed populations.
      The Wright-Fisher model is one of the most widely used models for this purpose.
      It describes the stochastic behavior in time of allele frequencies and the
      influence of evolutionary pressures, such as mutation and selection. Despite its
      simple mathematical formulation, exact results for the distribution of allele
      frequency (DAF) as a function of time are not available in closed analytical
      form. Existing approximations build on the computationally intensive diffusion
      limit or rely on matching moments of the DAF. One of the moment-based
      approximations relies on the beta distribution, which can accurately describe the
      DAF when the allele frequency is not close to the boundaries (0 and 1).
      Nonetheless, under a Wright-Fisher model, the probability of being on the
      boundary can be positive, corresponding to the allele being either lost or fixed.
      Here we introduce the beta with spikes, an extension of the beta approximation
      that explicitly models the loss and fixation probabilities as two spikes at the
      boundaries. We show that the addition of spikes greatly improves the quality of
      the approximation. We additionally illustrate, using both simulated and real
      data, how the beta with spikes can be used for inference of divergence times
      between populations with comparable performance to an existing state-of-the-art
      method. 

PMID- 26311475
TI  - A Coalescent Model for a Sweep of a Unique Standing Variant.
AB  - The use of genetic polymorphism data to understand the dynamics of adaptation and
      identify the loci that are involved has become a major pursuit of modern
      evolutionary genetics. In addition to the classical "hard sweep" hitchhiking
      model, recent research has drawn attention to the fact that the dynamics of
      adaptation can play out in a variety of different ways and that the specific
      signatures left behind in population genetic data may depend somewhat strongly on
      these dynamics. One particular model for which a large number of empirical
      examples are already known is that in which a single derived mutation arises and
      drifts to some low frequency before an environmental change causes the allele to
      become beneficial and sweeps to fixation. Here, we pursue an analytical
      investigation of this model, bolstered and extended via simulation study. We use
      coalescent theory to develop an analytical approximation for the effect of a
      sweep from standing variation on the genealogy at the locus of the selected
      allele and sites tightly linked to it. We show that the distribution of
      haplotypes that the selected allele is present on at the time of the
      environmental change can be approximated by considering recombinant haplotypes as
      alleles in the infinite-alleles model. We show that this approximation can be
      leveraged to make accurate predictions regarding patterns of genetic polymorphism
      following such a sweep. We then use simulations to highlight which sources of
      haplotypic information are likely to be most useful in distinguishing this model
      from neutrality, as well as from other sweep models, such as the classic hard
      sweep and multiple-mutation soft sweeps. We find that in general, adaptation from
      a unique standing variant will likely be difficult to detect on the basis of
      genetic polymorphism data from a single population time point alone, and when it
      can be detected, it will be difficult to distinguish from other varieties of
      selective sweeps. Samples from multiple populations and/or time points have the
      potential to ease this difficulty. 

PMID- 26311476
TI  - Endocrine-Disrupting Chemicals and Oil and Natural Gas Operations: Potential
      Environmental Contamination and Recommendations to Assess Complex Environmental
      Mixtures.
AB  - BACKGROUND: Hydraulic fracturing technologies, developed over the last 65 years,
      have only recently been combined with horizontal drilling to unlock oil and gas
      reserves previously deemed inaccessible. Although these technologies have
      dramatically increased domestic oil and natural gas production, they have also
      raised concerns for the potential contamination of local water supplies with the
      approximately 1,000 chemicals that are used throughout the process, including
      many known or suspected endocrine-disrupting chemicals. OBJECTIVES: We discuss
      the need for an endocrine component to health assessments for drilling-dense
      regions in the context of hormonal and antihormonal activities for chemicals
      used. METHODS: We discuss the literature on a) surface and groundwater
      contamination by oil and gas extraction operations, and b) potential human
      exposure, particularly in the context of the total hormonal and antihormonal
      activities present in surface and groundwater from natural and anthropogenic
      sources; we also discuss initial analytical results and critical knowledge gaps.
      DISCUSSION: In light of the potential for environmental release of oil and gas
      chemicals that can disrupt hormone receptor systems, we recommend methods for
      assessing complex hormonally active environmental mixtures. CONCLUSIONS: We
      describe a need for an endocrine-centric component for overall health assessments
      and provide information supporting the idea that using such a component will help
      explain reported adverse health trends as well as help develop recommendations
      for environmental impact assessments and monitoring programs.

PMID- 26311477
TI  - Revisiting the incremental effects of context on word processing: Evidence from
      single-word event-related brain potentials.
AB  - The amplitude of the N400-an event-related potential (ERP) component linked to
      meaning processing and initial access to semantic memory-is inversely related to
      the incremental buildup of semantic context over the course of a sentence. We
      revisited the nature and scope of this incremental context effect, adopting a
      word-level linear mixed-effects modeling approach, with the goal of probing the
      continuous and incremental effects of semantic and syntactic context on multiple
      aspects of lexical processing during sentence comprehension (i.e., effects of
      word frequency and orthographic neighborhood). First, we replicated the classic
      word-position effect at the single-word level: Open-class words showed reductions
      in N400 amplitude with increasing word position in semantically congruent
      sentences only. Importantly, we found that accruing sentence context had
      separable influences on the effects of frequency and neighborhood on the N400.
      Word frequency effects were reduced with accumulating semantic context. However,
      orthographic neighborhood was unaffected by accumulating context, showing robust
      effects on the N400 across all words, even within congruent sentences.
      Additionally, we found that N400 amplitudes to closed-class words were reduced
      with incrementally constraining syntactic context in sentences that provided only
      syntactic constraints. Taken together, our findings indicate that modeling word
      level variability in ERPs reveals mechanisms by which different sources of
      information simultaneously contribute to the unfolding neural dynamics of
      comprehension. 

PMID- 26311478
TI  - Spectroscopic analysis of aluminum chloride phthalocyanine in binary
      water/ethanol systems for the design of a new drug delivery system for
      photodynamic therapy cancer treatment.
AB  - This study evaluated the behavior of aluminum chloride phthalocyanine in a binary
      water/ethanol mixture using electronic absorption spectroscopy and static and
      time-resolved fluorescence spectroscopy. The electronic absorption spectra,
      resonance light scattering and fluorescence quenching of aluminum chloride
      phthalocyanine in water/ethanol mixtures were studied at several concentrations.
      The electronic absorption spectra and fluorescence quenching changed
      significantly at approximately 50% water (v/v). Below 50% water, the dimerization
      constant values were negative (-2609.2 M(-1) and -506.5 M(-1) at 30% and 40% of
      water, respectively), indicating that the formation of aggregates under these
      conditions is not favored. However, at 50% water, the dimerization constant value
      was estimated to be 559.7 M(-1), which indicates the presence of dimers. Above
      60% water, the aggregation process was responsible for the balance between large
      complexes (such as trimers, tetramers or oligomers) formed in the medium under
      these conditions. The appearance of new absorption bands at 387 nm and 802 nm and
      their bathochromic shift relative to the monomer bands suggested that some J-type
      aggregates form. These results are relevant to understanding the behavior and use
      of aluminum chloride phthalocyanine in the design of new drug delivery systems
      for clinical application in photodynamic therapy as a new approach to treat skin
      cancer.

PMID- 26311479
TI  - Spectroscopic, microchemical and petrographic analyses of plasters from ancient
      buildings in Lamezia Terme (Calabria, Southern Italy).
AB  - This work shows the results of the spectroscopic, microchemical and petrographic
      study carried out on six plasters coming from three important residential
      buildings of the 18th century, located in Lamezia Terme (Catanzaro, Southern
      Italy). To study the provenance of the raw materials used to make the plasters,
      one sample of limestone and two samples of sand were also collected from the
      quarries near Lamezia Terme and compared with the historical plasters. Samples
      were studied by polarized optical microscopy (OM), X-ray powder diffraction
      (XRPD), scanning electron microscopy (SEM) with energy dispersive X-ray
      spectroscopy (EDS) and Raman spectroscopy. The results of these analyses allowed
      to determine the mineralogical, petrographical and chemical characteristics of
      the plasters, identify the pigments used for their coloration and provide useful
      information about the building techniques, the raw materials employed and the
      production technology of plasters during the 18th century in Lamezia Terme. SEM
      EDS microanalysis also revealed the presence of gold and silver on the surface of
      two samples. 

PMID- 26311480
TI  - A simple ratiometric and colorimetric chemosensor for the selective detection of
      fluoride in DMSO buffered solution.
AB  - A derivative of squaramide (cyclobuta[b]quinoxaline-1, 2(3H, 8H)-dione) has been
      synthesized for the ratiometric and colorimetric sensing of F(-) in aqueous
      solution in competitive fashion. With F(-), probe 1 showed a highly selective
      naked-eye detectable color change along with a characteristic UV-Vis absorbance
      over other tested ions, which probably originates from the deprotonation occurred
      between 1 and F(-), as proved by the (1)H NMR titration experiments and DFT
      calculations. 

PMID- 26311481
TI  - Sleep quality among internally displaced Georgian adolescents and population
      based controls.
AB  - Sleep problems in children and adolescents are a significant public health
      concern and may be linked to a variety of psychoemotional difficulties. This
      study aimed to evaluate sleep quality and associated factors in conflict-affected
      Georgian adolescents after 9 months of forced displacement. Thirty-three
      internally displaced adolescents (mean age 11.4 years) and 33 adolescents (mean
      age 10.8 years) from the general population completed the Epworth Sleepiness
      Scale and the Children's Depression Inventory (CDI). Parents completed the
      Children's Sleep-Wake Scale and provided information on their socioeconomic
      status (SES) and the adolescents' sleep behavior, academic performance, and peer
      social relationships. The groups differed significantly in sleep quality, peer
      relationships, SES, and CDI scores. In the internally displaced group, the only
      significant predictor of sleep quality was SES, which increased the predictive
      capacity of the model (demographic and psychosocial variables) by 20% in the
      hierarchical analyses. The most significant predictor in the non-internally
      displaced group was CDI. This research indicates that displacement may affect
      sleep quality and psychosocial functioning. The importance of family SES as a
      contributing factor to displaced adolescents' poor sleep quality is highlighted.
      An integrated approach designed to improve the psychosocial environment of
      internally displaced adolescents is needed for their protection.

PMID- 26311482
TI  - Expectation prior to human papilloma virus vaccination: 11 to 12-Year-old girls'
      written narratives.
AB  - Expectations prior to needle-related procedures can influence individuals'
      decision making and compliance with immunization programmes. To protect from
      human papilloma virus (HPV) and cervical cancer, the immunization needs to be
      given before sexual debut raising interest for this study's aim to investigate
      how 11 to 12-year-old girls narrate about their expectations prior to HPV
      vaccination. A total of 27 girls aged 11 to 12 years participated in this
      qualitative narrative study by writing short narratives describing their
      expectations. The requirement for inclusion was to have accepted HPV vaccination.
      Data were subjected to qualitative content analysis. Findings showed the
      following expectations: going to hurt, going to be scared and going to turn out
      fine. The expectations were based on the girls' previous experiences, knowledge
      and self-image. The latent content revealed that the girls tried to transform
      uneasiness to confidence. The conclusion drawn from this study is that most girls
      of this age seem confident about their ability to cope with possible
      unpleasantness related to vaccinations. However, nurses need to find strategies
      to help those children who feel uneasy about needle-related procedures.

PMID- 26311483
TI  - Anxiety, depression, and quality of life in Iranian mothers of children with
      autism spectrum disorder.
AB  - Autism spectrum disorder (ASD) is being more recognized and diagnosed in
      developing as well as developed countries. We aimed to investigate the frequency
      of anxiety, depression, and quality of life in mothers of children with ASD in
      Iranian families. We conducted a descriptive cross-sectional study on demographic
      data and mental health characteristics of 127 mothers of children with ASD.
      Mothers of children with ASD had high levels of anxiety (72.4%), depression
      (49.6%), and low scores of health-related quality of life (HRQOL). There was
      strong association between the child's age and the severity of mother's
      depression and QOL. Duration since diagnosis of ASD positively correlated with
      maternal depression. Anxiety, depression, and low HRQOL are more common in
      Iranian mothers with autistic children in our study. Our findings have
      implications for further investigation in mental health status of mothers of
      children with ASD, and providing educational support and interventional
      strategies may improve the mental health status of the entire family.

PMID- 26311484
TI  - Association between risk behaviors and adiposity indicators in adolescents from
      Southern Brazil: A methodological approach.
AB  - The aim of this study was to analyze the association between risk behaviors and
      adiposity indicators in adolescents and to discuss some methodological aspects
      related to this relationship. We evaluated 1,321 adolescents (55.2% female) aged
      10-16 years. Relative body fat (%fat) by measurement of triceps and subscapular
      skinfold thickness and waist circumference (WC) were used as total and central
      adiposity indicators, respectively. Physical inactivity, time spent in front of
      the TV, the consumption of soda and/or chocolate, alcohol, and tobacco smoking
      were analyzed as risk behaviors. Information about the socioeconomic status
      (categorized into three levels) and nutritional status of the mother (overweight
      or normal weight) were used as adjustment factors in the analyses of prevalence
      ratio (PR) of the outcomes and their associated 95% confidence intervals (95%
      CI). The chi-square test and Poisson regression were used for statistical
      analyses. Low associations were found between risk behaviors and adiposity
      indicators. Tobacco smoking was the most positively correlated behavior with
      adiposity in girls (%fat: PR = 1.61; 95% CI = 1.04-2.47; WC: PR = 1.90; 95% CI =
      1.17-3.08) and in adolescents whose mothers were normal weight (%fat: PR = 2.31;
      95% CI = 1.33-4.03; WC: PR: 2.31; CI: 1.19-4.46). Additionally, as an important
      methodological issue, we highlighted the assessment of risk behaviors in
      adolescents as crucial to producing more robust evidence on the subject. Of the
      investigated behaviors, we concluded that tobacco smoking is the behavior most
      associated with adiposity indicators.

PMID- 26311485
TI  - The effects of massage therapy on physical growth and gastrointestinal function
      in premature infants: A pilot study.
AB  - To promote the growth and development of premature infants, effective and tender
      care is required in neonatal intensive care units (NICUs). The purpose of this
      study was to test the potential effects of massage therapy on increasing physical
      growth and promoting gastrointestinal function in premature infants. Twenty
      subjects were divided into two groups in the NICU of one general hospital located
      in South Korea. The experimental group (n = 10) were given massage therapy and
      the control group (n = 10) received routine care. Massage therapy was performed
      twice daily for 14 days, for 15 minutes per session. In the physical growth,
      height and chest circumference were significantly increased in the experimental
      group. In assessing gastrointestinal function, frequency of pre-feed gastric
      residual was significantly decreased and numbers of bowel movements were
      significantly increased in the experimental group. This study showed massage
      therapy has the potential effects on increasing physical growth and
      gastrointestinal function in premature infants. The massage in the NICU might be
      utilized as a part of developmental care, but more research needs to be done.
      NICU nurses need to be trained in massage therapy techniques to provide more
      effective clinical care for premature infants.

PMID- 26311486
TI  - Socio-demographic correlates of parents' participation in care of a hospitalized
      child: A perspective from a developing country.
AB  - Studies on parents' participation in care of a hospitalized child are rare and
      have not sufficiently addressed the factors prompting parents' participation in
      their child's care. This study investigated the relative contributions and
      predictive value of parents' and children's demographics on parents'
      participation in care. A convenience sample of 294 parents participated from four
      major hospitals in a metropolitan area in Amman. Parents completed two sets of
      measures, a socio-demographic form and the Arabic version of the Index of Parent
      Participation/Hospitalized Child. A series of bivariate analyses were completed
      to investigate associations between socio-demographic variables and parents'
      participation in care. The multiple regression analysis identified four variables
      as the optimal set of predictors for parent participation in the care of a
      hospitalized child: hospital experience, type of illness, child's age and type of
      hospital. The importance of interpreting these findings in a cultural context is
      discussed.

PMID- 26311487
TI  - Clinical indicators of ineffective airway clearance in children with acute
      respiratory infection.
AB  - The identification of clinical indicators with good predictive ability allows the
      nurse to minimize the existing variability in clinical situations presented by
      the patient and to accurately identify the nursing diagnosis, which represents
      the true clinical condition. The purpose of this study was to analyze the
      accuracy of NANDA-I clinical indicators of the nursing diagnosis ineffective
      airway clearance (IAC) in children with acute respiratory infection. This was a
      prospective cohort study conducted with a group of 136 children and followed for
      a period of time ranging from 6 to 10 consecutive days. For data analysis, the
      measures of accuracy were calculated for clinical indicators, which presented
      statistical significance in a generalized estimated equation model. IAC was
      present in 91.9% of children in the first assessment. Adventitious breath sounds
      presented the best measure of accuracy. Ineffective cough presented a high value
      of sensitivity. Changes in respiratory rate, wide-eyed, diminished breath sounds,
      and difficulty vocalizing presented high positive predictive values. In
      conclusion, adventitious breath sounds showed the best predictive ability to
      diagnose IAC in children with respiratory acute infection.

PMID- 26311488
TI  - Mice in an enriched environment learn more flexibly because of adult hippocampal
      neurogenesis.
AB  - We here show that living in a stimulus-rich environment (ENR) improves water maze
      learning with respect to specific key indicators that in previous loss-of
      function experiments have been shown to rely on adult hippocampal neurogenesis.
      Analyzing the strategies employed by mice to locate the hidden platform in the
      water maze revealed that ENR facilitated task acquisition by increasing the
      probability to use effective search strategies. ENR also enhanced the animals'
      behavioral flexibility, when the escape platform was moved to a new location.
      Treatment with temozolomide, which is known to reduce adult neurogenesis,
      abolished the effects of ENR on both acquisition and flexibility, while leaving
      other aspects of water maze learning untouched. These characteristic effects and
      interdependencies were not seen in parallel experiments with voluntary wheel
      running (RUN), a second pro-neurogenic behavioral stimulus. Since the
      histological assessment of adult neurogenesis is by necessity an end-point
      measure, the levels of neurogenesis over the course of the experiment can only be
      inferred and the present study focused on behavioral parameters as analytical
      endpoints. Although the correlation of physical activity with precursor cell
      proliferation and of learning and the survival of new neurons is well
      established, how the specific functional effects described here relate to dynamic
      changes in the stem cell niche remains to be addressed. Nevertheless, our
      findings support the hypothesis that adult neurogenesis is a critical mechanism
      underlying the beneficial effects of leading an active live, rich in experiences.

PMID- 26311489
TI  - The long-lasting love affair between the budding yeast Saccharomyces cerevisiae
      and the Epstein-Barr virus.
AB  - The Epstein-Barr gammaherpesvirus (EBV) is the first oncogenic virus discovered
      in human. Indeed, EBV has been known for more than 50 years to be tightly
      associated with certain human cancers. As such, EBV has been the subject of
      extensive studies aiming at deciphering various aspects of its biological cycle,
      ranging from the regulation of its genome replication and maintenance to the
      induction of its lytic cycle, including the mechanisms that allow its immune
      evasion or that are related to its tumorogenicity. For more than 30 years the
      budding yeast Saccharomyces cerevisiae has fruitfully contributed to a number of
      these studies. The aim of this article is to review the various aspects of EBV
      biology for which yeast has been instrumental, and to propose new possible
      applications for these yeast-based assays, as well as the creation of further
      yeast models dedicated to EBV. This review article illustrates the tremendous
      potential of S. cerevisiae in integrated chemobiological approaches for the
      biomedical research. 

PMID- 26311490
TI  - Iranian nurses' professional competence in spiritual care in 2014.
AB  - BACKGROUND: The holistic approach views the human as a bio-psycho-socio-spiritual
      being. Evidence suggests that among these dimensions, the spiritual one is
      largely ignored in healthcare settings. OBJECTIVES: This study aimed to evaluate
      Iranian nurses' perceived professional competence in spiritual care, the
      relationship between perceived competence and nurses' personal characteristics,
      and barriers to provide spiritual care. RESEARCH DESIGN: A cross-sectional study
      was conducted in the year 2014. Participants and research context: The study
      population consisted of nurses working in teaching hospitals in Kashan city.
      Using a stratified, systematic random method, 250 samples were selected from a
      total of 1400 nurses. An indigenous instrument was used to assess the nurses'
      competencies in spiritual care. Ethical considerations: A research ethics
      committee approved the study. All the participants were briefed on the study
      aims, were assured of the confidentiality of their personal information, and
      signed a written informed consent. RESULTS: Among a total of 250 nurses, 239
      answered the questionnaire completely, and in total, 23%, 51%, and 26% had poor,
      moderate, and favorable competence in spiritual care, respectively. No
      significant differences were found between the mean competence scores of
      spiritual care in terms of gender, marital status, employment status, and level
      of qualification. Significant difference was found between nurses' overall score
      of competence in spiritual care and receiving training on spiritual care, nurses'
      position, and the ward they worked in. DISCUSSION: Confirming the findings of the
      international literature, this study puts light on the situation of nurses'
      perceived competence and barriers to providing spiritual care in Iran as an
      eastern and Islamic context. CONCLUSION: Three-quarters of the nurses had
      moderate or unfavorable competence in spiritual care. Due to the crucial role of
      spiritual care in quality of care and patient satisfaction, nurses should be
      trained and supported to provide spiritual care.

PMID- 26311491
TI  - Recent advances in the study of active endogenous retrovirus envelope
      glycoproteins in the mammalian placenta.
AB  - Endogenous retroviruses (ERVs) are a component of the vertebrate genome and
      originate from exogenous infections of retroviruses in the germline of the host.
      ERVs have coevolved with their hosts over millions of years. Envelope
      glycoproteins of endogenous retroviruses are often expressed in the mammalian
      placenta, and their potential function has aroused considerable research
      interest, including the manipulation of maternal physiology to benefit the fetus.
      In most mammalian species, trophoblast fusion in the placenta is an important
      event, involving the formation of a multinucleated syncytiotrophoblast layer to
      fulfill essential fetomaternal exchange functions. The key function in this
      process derives from the envelope genes of endogenous retroviruses, namely
      syncytins, which show fusogenic properties and placenta-specific expression. This
      review discusses the important role of the recognized endogenous retrovirus
      envelope glycoproteins in the mammalian placenta. 

PMID- 26311492
TI  - Investigation of the genotype III to genotype I shift in Japanese encephalitis
      virus and the impact on human cases.
AB  - Japanese encephalitis is a mosquito borne disease and is the leading cause of
      viral encephalitis in the Asia-Pacific area. The causative agent, Japanese
      encephalitis virus (JEV) can be phylogenetically classified into five genotypes
      based on nucleotide sequence. In recent years, genotype I (GI) has displaced
      genotype III (GIII) as the dominant lineage, but the mechanisms behind this
      displacement event requires elucidation. In an earlier study, we compared host
      variation over time between the two genotypes and observed that GI appears to
      have evolved to achieve more efficient infection in hosts in the replication
      cycle, with the tradeoff of reduced infectivity in secondary hosts such as
      humans. To further investigate this phenomenon, we collected JEV surveillance
      data on human cases and, together with sequence data, and generated genotype/case
      profiles from seven Asia-Pacific countries and regions to characterize the
      GI/GIII displacement event. We found that, when comprehensive and consistent
      vaccination and surveillance data was available, and the GIII to GI shift
      occurred within a well-defined time period, there was a statistically significant
      drop in JEV human cases. Our findings provide further support for the argument
      that GI is less effective in infecting humans, who represent a dead end host.
      However, experimental investigation is necessary to confirm this hypothesis. The
      study highlights the value of alternative approaches to investigation of
      epidemics, as well as the importance of effective data collection for disease
      surveillance and control. 

PMID- 26311493
TI  - Do Talkativeness and Vocal Loudness Correlate With Laryngeal Pathology? A Study
      of the Vocal Overdoer/Underdoer Continuum.
AB  - OBJECTIVES: Assess the correlation between self-rating scales of talkativeness
      and loudness with various types of voice disorders. DESIGN: This is a
      retrospective study. METHODS: A total of 974 patients were analyzed. The cohort
      study included 430 consecutive patients presenting to the senior author with
      voice complaints from December 1995 to December 1998. The case-control study
      added 544 consecutive patients referred to the same examiner from January 1988 to
      December 1998 for vocal fold examination before thyroid, parathyroid, and carotid
      surgery. Patient responses on seven-point Likert self-rating scales of
      talkativeness and loudness were compared with laryngeal disease. RESULTS: Mucosal
      lesions clearly associated with vibratory trauma are strongly associated with a
      high self-rating of talkativeness. Laryngeal deconditioning disorders were
      associated with a low self-rating of talkativeness. CONCLUSIONS: Use of a simple
      self-rating scale of vocal loudness and talkativeness during history taking can
      reliably orient the examiner to the types of voice disorders likely to be
      diagnosed subsequently during vocal capability testing and visual laryngeal
      examination. The high degree of talkativeness and loudness seen in vocal
      overdoers correlates well with mucosal disorders such as nodules, polyps,
      capillary ectasia, epidermoid inclusion cysts, and hemorrhage. A lower degree of
      talkativeness correlates with muscle deconditioning disorders such as vocal fold
      bowing, atrophy, presbyphonia, and vocal fatigue syndrome.

PMID- 26311494
TI  - Comparative Efficacy and Safety of Laparoscopic Greater Curvature Plication and
      Laparoscopic Sleeve Gastrectomy: A Meta-analysis.
AB  - Laparoscopic greater curvature plication (LGCP) is considered to have evolved
      from less invasive laparoscopic sleeve gastrectomy (LSG). In the present meta
      analysis, we compared these two procedures in terms of efficacy and safety. We
      searched PubMed, Embase, and the Cochrane Library from database inception until
      April 2015. Excess weight loss (%EWL), resolution of obesity-related
      comorbidities, adverse events, operation time, and postoperative hospital stay
      were evaluated using the software Review Manager 5.3. The following four studies
      were eligible for inclusion: one randomized controlled trial and three non
      randomized controlled trials involving 299 patients. Our meta-analysis
      demonstrated a significantly greater %EWL after LSG than LGCP at the follow-up
      time points of 3 months (Z = 2.26, p = 0.02), 6 months (Z = 4.49, p < 0.00001),
      and 12 months (Z = 6.99, p < 0.00001). The difference in the resolution of
      diabetes mellitus between these two approaches did not reach statistical
      significance (p = 0.66). According to the pooled data, LGCP was associated with
      more adverse events than was LSG (p = 0.01). The operation time (p = 0.54) and
      postoperative hospital stay (p = 0.44) were comparable between the two groups.
      LGCP is inferior to LSG not only in terms of providing effective weight loss but
      also in terms of safety.

PMID- 26311495
TI  - Reply to: What Causes Late Perforation of the Jejuno-jejunal Anastomosis After
      Roux-en-Y Gastric Bypass Surgery?

PMID- 26311496
TI  - An exploratory qualitative investigation of psychosocial determinants of parental
      decisions to support sport participation for youth with a mobility impairment.
AB  - INTRODUCTION: Parents of youth with a mobility impairment (MI) have an important
      influence on their children's sport participation. The current study consists of
      an exploratory qualitative investigation of the relevance of HAPA for
      understanding parental support behaviours for youth with MI's sport
      participation. METHODS: Parents of youth athletes (Mage=11.10; SD=2.77) and non
      athletes (Mage=11.50; SD=3.84) participated in semi-structured interviews with
      question development guided by the Health Action Process Approach (HAPA).
      RESULTS: Constructs from HAPA were expressed as relevant to parental decisions,
      with differing subthemes emerging based upon parental group (i.e. parents of non
      athletes or parents of athletes). Other constructs that emerged included
      barriers, facilitators, and resources. DISCUSSION: Constructs from the
      motivational phase of HAPA were relevant for parents of athletes and non
      athletes, while the volitional phase demonstrated utility for understanding the
      views of parents of athletes. Differences between the patterns of responses of
      both groups were apparent in how the constructs were expressed. Findings identify
      key areas for research, as well as practical applications. For example, future
      programs can target parental positions on specific HAPA constructs (e.g. risk
      perceptions) where differences were found between both groups of parents in order
      to promote parental decisions that support their children's sport participation.

PMID- 26311497
TI  - PAQR3 modulates cholesterol homeostasis by anchoring Scap/SREBP complex to the
      Golgi apparatus.
AB  - Cholesterol biosynthesis is regulated by transcription factors SREBPs and their
      escort protein Scap. On sterol depletion, Scap/SREBP complex is transported from
      endoplasmic reticulum (ER) to the Golgi apparatus where SREBP is activated. Under
      cholesterol sufficient condition, Insigs act as anchor proteins to retain
      Scap/SREBP in the ER. However, the anchor protein of Scap/SREBP in the Golgi is
      unknown. Here we report that a Golgi-localized membrane protein progestin and
      adipoQ receptors 3 (PAQR3) interacts with Scap and SREBP and tethers them to the
      Golgi. PAQR3 promotes Scap/SREBP complex formation, potentiates SREBP processing
      and enhances lipid synthesis. The mutually exclusive interaction between Scap and
      PAQR3 or Insig-1 is regulated by cholesterol level. PAQR3 knockdown in liver
      blunts SREBP pathway and decreases hepatic cholesterol content. Disrupting the
      interaction of PAQR3 with Scap/SREBP by a synthetic peptide inhibits SREBP
      processing and activation. Thus, PAQR3 regulates cholesterol homeostasis by
      anchoring Scap/SREBP to the Golgi and disruption of such function reduces
      cholesterol biosynthesis. 

PMID- 26311498
TI  - Octyl-modified magnetic graphene as a sorbent for the extraction and simultaneous
      determination of fragrance allergens, musks, and phthalates in aqueous samples by
      gas chromatography with mass spectrometry.
AB  - An effective, simple, and low-cost sample preparation method based on dispersive
      SPE followed by GC with MS is developed for the multianalyte determination of
      fragrance allergens, musks, and phthalates, at sub-ppb levels. The extraction
      procedure is based on a novel magnetic graphene sorbent, which is functionalized
      with octylamine, taking advantage of the functionalization's hydrophobic
      properties and pi-pi interactions with the analytes. Two alkyl amines, the
      octylamine and octadecylamine are studied to introduce alkyl chains in the basal
      plane of graphene. Magnetic graphene- octadecylamine is proved to be highly
      hydrophobic to such a degree that is hard to disperse in the bulk aqueous
      matrixes. Because of this behavior, its extraction efficiency for the target
      analytes is low. The synthesis and applicability of the magnetic graphene
      octylamine as more favored sorbent are optimized in terms of the most determining
      experimental conditions. The detection and quantification limits, which are
      calculated based on S/N ratio of 3 and 10, respectively, ranged from 0.29 to 3.2
      ng L(-1) and from 0.89 to 9.6, respectively. The dispersive SPE is successfully
      applied to routine analysis for the determination of the target analytes in
      samples from municipal treatment plant of Ioannina (Greece), from Pamvotis Lake
      and baby bathwater. The reproducibility of the spiked biological treatment plant
      water sample is evaluated and the relative standard deviation values range
      between 2.1 and 9.4%. 

PMID- 26311499
TI  - Medical comorbidity and medical complications associated with binge-eating
      disorder.
AB  - OBJECTIVE: The purpose of this review is to provide an overview of possible
      medical complications of binge-eating disorder (BED). METHOD: Literature on BED,
      both in obese and nonobese patients, was reviewed. RESULTS: A growing literature
      suggests that BED independently may increase the likelihood of developing
      components of the metabolic syndrome, and that LOC eating in children may
      contribute to weight gain and metabolic disturbances. Limited evidence suggests
      that other organ systems may be affected by BED as well. DISCUSSION: Additional
      prospective studies are needed. Although the results of the available studies are
      not definitive and provide somewhat mixed results, there does appear to be a
      clear suggestion of an increased risk for the development of components of the
      metabolic syndrome in adults and children.

PMID- 26311500
TI  - Protocol-directed weaning from mechanical ventilation in neurological patients: a
      randomised controlled trial and subgroup analyses based on consciousness.
AB  - OBJECTIVES: To assess whether a weaning protocol reduces the mechanical
      ventilation (MV) duration compared to physician's judgement-based weaning in
      neurological patients and to determine whether patient consciousness influences
      this reduction. METHODS: A randomised controlled trial was conducted in a
      neurological intensive care unit (NCU) of a tertiary hospital; 144 patients
      requiring MV for more than 24 hours were randomly allocated to protocol-directed
      (intervention) (n = 71) or physician-directed (control) group (n = 73). RESULTS:
      The intervention group displayed a significantly shorter median weaning time than
      the control group (2.00 vs 5.07 days, P < 0.05). The median MV duration tended to
      be shorter in the intervention group (10.8 vs 14.2 days, P = 0.106). The median
      length of NCU stay was 19.0 and 26.1 days in the intervention and control groups,
      respectively (P = 0.063). The median NCU cost was 9.26 * 10(4) and 12.24 * 10(4)
      Y in the intervention and control groups, respectively (P = 0.059). The
      unsuccessful weaning, ventilator-associated pneumonia (VAP) and mortality rates
      were similar between the groups. Among conscious patients, the median weaning
      time (2.00 vs 7.00 days, P < 0.05) and the median MV duration (8.8 vs 18.0 days,
      P = 0.017) were significantly reduced in the intervention group. Among
      unconscious patients, the intervention group displayed a reduced median weaning
      time (1.00 vs 3.10 days, P < 0.05), but not median MV duration (11.6 vs 11.1
      days, P = 0.702), compared to the control group. CONCLUSION: Protocol-directed
      weaning reduces weaning time, MV duration, length of NCU stay and NCU cost in
      neurological patients, and these effects are more significant in conscious
      patients than in unconscious patients.

PMID- 26311501
TI  - The failing human heart is characterized by decreased numbers of telocytes as
      result of apoptosis and altered extracellular matrix composition.
AB  - Telocytes (TCs) are a novel type of interstitial cells only recently described.
      This study aimed at characterizing and quantifying TCs and telopodes (Tps) in
      normal and diseased hearts. We have been suggested that TCs are influenced by the
      extracellular matrix (ECM) composition. We used transmission electron microscopy
      and c-kit immunolabelling to identify and quantify TCs in explanted human hearts
      with heart failure (HF) because of dilated, ischemic or inflammatory
      cardiomyopathy. LV myectomy samples from patients with aortic stenosis with
      preserved ejection fraction and samples from donor hearts which could not be used
      for transplantation served as controls. Quantitative immunoconfocal analysis
      revealed that 1 mm(2) of the normal myocardium contains 14.9 +/- 3.4 TCs and 41.6
      +/- 5.9 Tps. As compared with the control group, the number of TCs and Tps in HF
      decreased more than twofold. There were no differences between HF and control in
      the number of Ki67-positive TCs. In contrast, terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labelling-positive TCs increased threefold in
      diseased hearts as compared to control. Significant inverse correlations were
      found between the amount of mature fibrillar collagen type I and the number of
      TCs (r = -0.84; P < 0.01) and Tps (r = -0.85; P < 0.01). The levels of degraded
      collagens showed a significant positive relationship with the TCs numbers. It is
      concluded that in HF the number of TCs are decreased because of higher rates of
      TCs apoptosis. Moreover, our results indicate that a close relationship exists
      between TCs and the ECM protein composition such that the number of TCs and Tps
      correlates negatively with the amount of mature fibrillar collagens and
      correlates positively with degraded collagens.

PMID- 26311502
TI  - Managing inadequate antidepressant response in depressive illness.
AB  - INTRODUCTION OR BACKGROUND: Depression frequently fails to respond to initial
      treatment. SOURCES OF DATA: Predominantly meta-analyses and RCTs but supplemented
      where necessary by additional data and the authors' clinical experience. AREAS OF
      AGREEMENT: A systematic assessment to identify remedial causes of poor response
      should be followed by planned sequential treatment trials. Joint decision making
      by the patient and clinician is essential. Strategies with the strongest support
      are antidepressant augmentation with lithium or second generation antipsychotics
      and adding cognitive behavioural treatment. Electroconvulsive therapy is highly
      effective in resistant depression but there is a high relapse rate when treatment
      ends. AREAS OF CONTROVERSY: Some pharmacological strategies have inconsistent
      data (e.g. antidepressant combinations, T3 augmentation) or limited preliminary
      data (e.g. ketamine, antidepressant augmentation with pramipexole). The efficacy
      of vagus nerve stimulation, deep brain stimulation and repetitive transcranial
      magnetic stimulation is unclear. GROWING POINTS: A greater understanding of the
      causes of depression may assist the development of more effective treatments.
      AREAS TIMELY FOR DEVELOPING RESEARCH: Role of glutamate antagonists and
      psychological treatments, other than cognitive behavioural therapy, as adjunctive
      treatments.

PMID- 26311503
TI  - Management of hip fracture.
AB  - INTRODUCTION: Hip fracture poses a significant global challenge both to
      healthcare systems and to patients themselves. We outline the management of this
      injury, highlight areas where the evidence is deficient and discuss research
      efforts towards improving the quality of the evidence base. SOURCES OF DATA: We
      searched MEDLINE, PubMed and the Cochrane Library, using the core search terms
      'hip fracture' and 'proximal femoral fracture'. In addition we reviewed national
      treatment guidelines for hip fracture care and references from relevant articles.
      Only articles published in English from inception to March 2015 were included.
      AREAS OF AGREEMENT: Modern hip fracture management should consist of a
      coordinated multidisciplinary approach with orthogeriatrician input, early
      surgery, adequate analgesia and liaison with related services to facilitate safe
      supported discharge. AREAS OF CONTROVERSY: The optimum thromboprophylaxis to
      reduce venous thromboembolism remains a topic for debate. The use of bone cement
      has received much attention recently with concerns about its safety in the
      frailest of hip fracture patients. GROWING POINTS: An increasing understanding of
      the severity and impact of sustaining a hip fracture upon quality of life. AREAS
      TIMELY FOR DEVELOPING RESEARCH: Strategies to improve postoperative mobility,
      postoperative nutrition and the role of home-based rehabilitation. There is a
      need to identify the optimum analgesic regimes and assessment tools for hip
      fracture patients with cognitive impairment.

PMID- 26311504
TI  - Advances in radionuclide imaging of cardiac sarcoidosis.
AB  - INTRODUCTION: Radionuclide imaging for the diagnosis and monitoring of cardiac
      involvement in sarcoidosis has advanced significantly in recent years. SOURCES OF
      DATA: This article is based on published clinical guidelines, literature review
      and our collective clinical experience. AREAS OF AGREEMENT: Gallium-67
      scintigraphy is among the diagnostic criteria for cardiac involvement in systemic
      sarcoidosis, and it is strongly associated with response to treatment. However,
      fluorine-18, 2-fluoro-deoxyglucose (FDG) positron emission tomography (PET) is
      now preferred both for diagnosis and for assessing prognosis. AREAS OF
      CONTROVERSY: Most data are from small observational studies that are potentially
      biased. GROWING POINTS: Quantitative imaging to assess changes in disease
      activity in response to treatment may lead to FDG-PET having an important routine
      role in managing cardiac sarcoidosis. AREAS TIMELY FOR DEVELOPING RESEARCH:
      Larger prospective studies are required, particularly to assess the effectiveness
      of radionuclide imaging in improving clinical management and outcome.

PMID- 26311505
TI  - New vascular plant records for the Canadian Arctic Archipelago.
AB  - The Canadian Arctic Archipelago is a vast region of approximately 1,420,000
      km(2), with a flora characterized by low species diversity, low endemicity, and
      little influence by alien species. New records of vascular plant species are
      documented here based on recent fieldwork on Victoria and Baffin Islands;
      additional records based on recent literature sources are mentioned. This paper
      serves as an update to the 2007 publication Flora of the Canadian Arctic
      Archipelago, and brings the total number of vascular plants for the region to 375
      species and infraspecific taxa, an increase of 7.7%. Three families
      (Amaranthaceae, Juncaginaceae, Pteridaceae) and seven genera (Cherleria L.,
      Cryptogramma R. Br., Platanthera Rich., Sabulina Rchb., Suaeda Forssk. ex J.F.
      Gmel., Triglochin L., Utricularia L.) are added to the flora, and one genus is
      deleted (Minuartia L.). Five species are first records for Nunavut
      (Arenarialongipedunculata Hulten, Cryptogrammastelleri (S.G. Gmel.) Prantl,
      Puccinelliabanksiensis Consaul, Saxifragaeschscholtzii Sternb.,
      Utriculariaochroleuca R.W. Hartm.). 

PMID- 26311506
TI  - First trimester interleukin-6 levels help to predict adverse pregnancy outcomes
      in both thyroid autoantibody positive and negative patients.
AB  - AIM: The aim of the present study is to compare pregnancy outcomes among patients
      with and without thyroid antibodies and/or subclinical hypothyroidism and
      investigate whether there is an association between first trimester maternal
      plasma interleukin-6 (IL-6) levels and adverse pregnancy outcomes. METHODS: A
      case-control study was carried out including 83 pregnant women (40 thyroid
      antibody positive and 43 healthy controls). The predictive value of first
      trimester maternal plasma IL-6 levels on adverse pregnancy outcomes were
      investigated. The optimal cut-off points of IL-6 for determining maternal and
      fetal outcomes were evaluated by receiver operating characteristic analyses.
      RESULTS: Compared with the control, median IL-6 levels were significantly higher
      in thyroid antibody positive pregnancies (median 1.58 vs 1.63 pg/mL; P = 0.047).
      IL-6 levels were found to be significantly higher in women who had suffered a
      miscarriage (P = 0.002), preterm delivery (P < 0.001), intrauterine growth
      restriction (P = 0.047), preterm premature rupture of membranes (P = 0.043) and
      overall prenatal complications (P < 0.001). A statistically significant negative
      correlation between gestational week at birth and IL-6 levels was also determined
      among all participants involved in the study (r = -0.385, P < 0.001). CONCLUSION:
      IL-6 levels are significantly increased in thyroid antibody positive patients and
      predictive for future adverse outcomes, irrespective of thyroid autoimmunity.
      Increased first trimester IL-6 levels independently predict adverse pregnancy
      outcomes, regardless of subclinical hypothyroidism.

PMID- 26311508
TI  - Statin-modified dendritic cells regulate humoral immunity in experimental
      autoimmune myasthenia gravis.
AB  - We previously demonstrated that atorvastatin induced immature dendritic cells
      (DCs) derived from spleen in vitro. Administration of these tolerogenic DCs led
      to amelioration of experimental autoimmune myasthenia gravis (EAMG). The
      protective effect was mainly mediated by inhibited cellular immune response,
      including up-regulated regulatory T cells and shifted Th1/Th17 to Th2 cytokines.
      The present study employed atorvastatin-modified bone marrow-derived DCs (AT
      BMDCs) to explore the effect of tolerogenic DCs on humoral immune response of
      EAMG and further elucidate the underlying mechanisms. Our data showed that AT
      BMDCs reduced the quantity and the relative affinity of pathogenic antibodies,
      suppressed germinal center response, decreased follicular helper T cells and IL
      21, and increased regulatory B cells. These results suggest that AT-BMDCs
      ameliorate EAMG by regulating humoral immune response, thus providing new
      insights into therapeutic approaches of myasthenia gravis and other autoimmune
      diseases. 

PMID- 26311509
TI  - Wnt5a inhibits K(+) currents in hippocampal synapses through nitric oxide
      production.
AB  - Hippocampal synapses play a key role in memory and learning processes by inducing
      long-term potentiation and depression. Wnt signaling is essential in the
      development and maintenance of synapses via several mechanisms. We have
      previously found that Wnt5a induces the production of nitric oxide (NO), which
      modulates NMDA receptor expression in the postsynaptic regions of hippocampal
      neurons. Here, we report that Wnt5a selectively inhibits a voltage-gated K(+)
      current (Kv current) and increases synaptic activity in hippocampal slices.
      Further supporting a specific role for Wnt5a, the soluble Frizzled receptor
      protein (sFRP-2; a functional Wnt antagonist) fully inhibits the effects of
      Wnt5a. We additionally show that these responses to Wnt5a are mediated by
      activation of a ROR2 receptor and increased NO production because they are
      suppressed by the shRNA-mediated knockdown of ROR2 and by 7-nitroindazole, a
      specific inhibitor of neuronal NOS. Together, our results show that Wnt5a
      increases NO production by acting on ROR2 receptors, which in turn inhibit Kv
      currents. These results reveal a novel mechanism by which Wnt5a may regulate the
      excitability of hippocampal neurons. 

PMID- 26311510
TI  - The use of megaprosthesis in the treatment of periprosthetic knee fractures.
AB  - PURPOSE: The optimum treatment for periprosthetic fractures in the region of the
      distal femur is undefined. Although internal fixation for prostheses which are
      stable is commonly utilised, this can lead to very prolonged morbidity and
      failure of the fracture to unite. Where the prosthesis is either loose or
      infected, revision surgery is required and a 'tumour type' prosthesis can be
      successfully utilised. METHODS: The outcome of 27 patients treated by an
      endoprosthetic replacement for periprosthetic fracture of the distal femur
      between 1988 and 2013 are reported. Two cases were treated by two-stage revision
      due to persistent infection. Clinical outcomes were assessed by Knee Society
      score and Knee Society pain scores. RESULTS: All 27 patients mobilised rapidly in
      the post-operative period and infection where present was eradicated by the
      technique. There have been no cases of further revision in the patients where
      clinical follow-up is available. Knee Society scores following treatment averaged
      88 and pain scores 43 at six months post-operatively. Eight patients have died
      during the long study period reflecting the age of the study population.
      CONCLUSIONS: The use of a tumour-type endoprosthesis in situations of comminuted
      periprosthetic fractures associated with a loose prosthesis shows favourable
      results with low complication rates and rapid mobilisation.

PMID- 26311511
TI  - Periprosthetic acetabular fractures.
AB  - PURPOSE: The aim of this article is to propose a diagnostic and therapeutic
      algorithm for the acetabular periprosthetic fractures. METHODS: This article
      explores the current literature on the epidemiology, causes and classification of
      periprosthetic acetabular fractures. Integrating data with the experience of the
      authors, it offers a guide to diagnosis and possible therapeutic strategies.
      RESULTS: Intra-operative fractures can occur during rasping, reaming or implant
      impaction, and they must be treated immediately if the component(s) is (are)
      unstable. Post-operative fractures can be due to major trauma (acute fractures)
      or minor forces in bone osteolysis; it is possible to plan reconstruction and
      fixation according to fracture characteristics. Treatment choice depends upon
      fracture site and implant stability. CONCLUSIONS: Periprosthetic acetabular
      fractures are uncommon complications that can occur intra-operatively or post
      operatively, and a reconstructive surgeon must be able to manage the procedure.
      Accurate planning and reconstruction implant are necessary to achieve good cup
      stability.

PMID- 26311512
TI  - Supracondylar humeral fractures in children: current concepts for management and
      prognosis.
AB  - Supracondylar humeral fractures are the most common elbow fractures in children
      and represent 3 % of all paediatric fractures. The most common cause is a fall
      onto an outstretched hand with the elbow in extension, resulting in an extension
      type fracture (97-99 % of cases). Currently, the Gartland classification is used,
      which has treatment implications. Diagnosis is based on plain radiographs, but
      accurate imaging could be limited due to patient pain. Based on fracture type,
      the definitive treatment could be either non-operative (type I) or operative
      (type III/IV); however, when handling type II fractures controversy remains.
      Neither pin configuration have shown higher efficacy over the other.
      Complications are ~1 %, the most common being pin migration, with compartment
      syndrome as the most devastating. Overall, functional outcomes are good, and
      physical therapy does not appear to be necessary.

PMID- 26311513
TI  - Crosstalk between epithelial-mesenchymal transition and castration resistance
      mediated by Twist1/AR signaling in prostate cancer.
AB  - Although invasive and metastatic progression via the epithelial-mesenchymal
      transition (EMT) and acquisition of resistance to castration are both critical
      steps in prostate cancer, the molecular mechanism of this interaction remains
      unclear. In this study, we aimed to elucidate the interaction of signaling
      between castration resistance and EMT, and to apply this information to the
      development of a novel therapeutic concept using transforming growth factor-beta
      (TGF-beta) inhibitor SB525334 combined with androgen-deprivation therapy against
      prostate cancer using an in vivo model. This study revealed that an EMT inducer
      (TGF-beta) induced full-length androgen receptor (AR) and AR variant expression.
      In addition, a highly invasive clone showed augmented full-length AR and AR
      variant expression as well as acquisition of castration resistance. Conversely,
      full-length AR and AR as well as Twist1 and mesenchymal molecules variant
      expression were up-regulated in castration-resistant LNCaP xenograft. Finally,
      TGF-beta inhibitor suppressed Twist1 and AR expression as well as prostate cancer
      growth combined with castration. Taken together, these results demonstrate that
      Twist1/AR signaling was augmented in castration resistant as well as mesenchymal
      phenotype prostate cancer, indicating the molecular mechanism of mutual and
      functional crosstalk between EMT and castration resistance, which may play a
      crucial role in prostate carcinogenesis and progression. 

PMID- 26311514
TI  - Evacuation of Intensive Care Units During Disaster: Learning From the Hurricane
      Sandy Experience.
AB  - OBJECTIVE: Data on best practices for evacuating an intensive care unit (ICU)
      during a disaster are limited. The impact of Hurricane Sandy on New York City
      area hospitals provided a unique opportunity to learn from the experience of ICU
      providers about their preparedness, perspective, roles, and activities. METHODS:
      We conducted a cross-sectional survey of nurses, respiratory therapists, and
      physicians who played direct roles during the Hurricane Sandy ICU evacuations.
      RESULTS: Sixty-eight health care professionals from 4 evacuating hospitals
      completed surveys (35% ICU nurses, 21% respiratory therapists, 25% physicians-in
      training, and 13% attending physicians). Only 21% had participated in an ICU
      evacuation drill in the past 2 years and 28% had prior training or real-life
      experience. Processes were inconsistent for patient prioritization, tracking,
      transport medications, and transport care. Respondents identified communication
      (43%) as the key barrier to effective evacuation. The equipment considered most
      helpful included flashlights (24%), transport sleds (21%), and oxygen tanks and
      respiratory therapy supplies (19%). An evacuation wish list included walkie
      talkies/phones (26%), lighting/electricity (18%), flashlights (10%), and portable
      ventilators and suction (16%). CONCLUSIONS: ICU providers who evacuated
      critically ill patients during Hurricane Sandy had little prior knowledge of
      evacuation processes or vertical evacuation experience. The weakest links in the
      patient evacuation process were communication and the availability of practical
      tools. Incorporating ICU providers into hospital evacuation planning and
      training, developing standard evacuation communication processes and tools, and
      collecting a uniform dataset among all evacuating hospitals could better inform
      critical care evacuation in the future.

PMID- 26311515
TI  - An equation to estimate the difference between theoretically predicted and SDS
      PAGE-displayed molecular weights for an acidic peptide.
AB  - The molecular weight (MW) of a protein can be predicted based on its amino acids
      (AA) composition. However, in many cases a non-chemically modified protein shows
      an SDS PAGE-displayed MW larger than its predicted size. Some reports linked this
      fact to high content of acidic AA in the protein. However, the exact relationship
      between the acidic AA composition and the SDS PAGE-displayed MW is not
      established. Zebrafish nucleolar protein Def is composed of 753 AA and shows an
      SDS PAGE-displayed MW approximately 13 kDa larger than its predicted MW. The
      first 188 AA in Def is defined by a glutamate-rich region containing ~35.6% of
      acidic AA. In this report, we analyzed the relationship between the SDS PAGE
      displayed MW of thirteen peptides derived from Def and the AA composition in each
      peptide. We found that the difference between the predicted and SDS PAGE
      displayed MW showed a linear correlation with the percentage of acidic AA that
      fits the equation y = 276.5x - 31.33 (x represents the percentage of acidic AA,
      11.4% <= x <= 51.1%; y represents the average DeltaMW per AA). We demonstrated
      that this equation could be applied to predict the SDS PAGE-displayed MW for
      thirteen different natural acidic proteins. 

PMID- 26311516
TI  - Large hemangiopericytoma of the pelvis--towards a multidisciplinary approach.
AB  - BACKGROUND: In 1942, Stout described tumors which derive from Zimmerman's
      pericytes and suggested the term hemangiopericytoma (HPC). These tumors, which
      are often highly vascularized, pose difficulties in the surgical management
      regarding blood loss and complete resection. Therefore, preoperative management
      seems to be an essential part in dealing with these issues. CASE PRESENTATION: We
      present a 70-year-old female patient with a large HPC in the pelvis. Preoperative
      embolization of the tumor was performed, and 2 weeks after the intervention, we
      completely resected the tumor with minimal blood loss. CONCLUSION: In which cases
      do we need preoperative treatment, especially emboliziation of
      hemangiopericytomas/solid fibrous tumors (SFT)? Although preoperative
      embolizations of tumors are now commonly undertaken, as for now, neither a clear
      statement nor a standardized approach has been given or developed. The purpose of
      this article is to provide our experience with preoperative embolization and to
      start a new discussion concerning a standardized approach.

PMID- 26311518
TI  - Erratum. Nurses' perceived and actual level of diabetes mellitus knowledge:
      results of a cluster analysis.

PMID- 26311519
TI  - Erratum. Factors affecting nursing staff in practicing spiritual care.

PMID- 26311517
TI  - Fatty acid binding protein deletion suppresses inflammatory pain through
      endocannabinoid/N-acylethanolamine-dependent mechanisms.
AB  - BACKGROUND: Fatty acid binding proteins (FABPs) serve as intracellular carriers
      that deliver endocannabinoids and N-acylethanolamines to their catabolic enzymes.
      Inhibition of FABPs reduces endocannabinoid transport and catabolism in cells and
      FABP inhibitors produce antinociceptive and anti-inflammatory effects in mice.
      Potential analgesic effects in mice lacking FABPs, however, have not been tested.
      FINDINGS: Mice lacking FABP5 and FABP7, which exhibit highest affinities for
      endocannabinoids, possessed elevated levels of the endocannabinoid anandamide and
      the related N-acylethanolamines palmitoylethanolamide and oleoylethanolamide.
      There were no compensatory changes in the expression of other FABPs or in
      endocannabinoid-related proteins in the brains of FABP5/7 knockout mice. These
      mice exhibited reduced nociception in the carrageenan, formalin, and acetic acid
      tests of inflammatory and visceral pain. The antinociceptive effects in FABP5/7
      knockout mice were reversed by pretreatment with cannabinoid receptor 1,
      peroxisome proliferator-activated receptor alpha, and transient receptor
      potential vanilloid 1 receptor antagonists in a modality specific manner. Lastly,
      the knockout mice did not possess motor impairments. CONCLUSIONS: This study
      demonstrates that mice lacking FABPs possess elevated levels of N
      acylethanolamines, consistent with the idea that FABPs regulate the
      endocannabinoid and N-acylethanolamine tone in vivo. The antinociceptive effects
      observed in the knockout mice support a role for FABPs in regulating nociception
      and suggest that these proteins should serve as targets for the development of
      future analgesics.

PMID- 26311520
TI  - Erratum. Exploring risk factors for depression among older men residing in Macau.

PMID- 26311521
TI  - Retraction statement: Manuka honey vs. hydrogel - a prospective, open label,
      multicentre, randomised controlled trial to compare desloughing efficacy and
      healing outcomes in venous ulcers.
AB  - The following article from Journal of Clinical Nursing, 'Manuka honey vs.
      hydrogel - a prospective, open label, multicentre, randomised controlled trial to
      compare desloughing efficacy and healing outcomes in venous ulcers' by Georgina
      Gethin and Seamus Cowman published online on 25 August 2008 in Wiley Online
      Library (wileyonlinelibrary.com) and in Volume 18, pp. 466-474, has been
      retracted by agreement between the journal Editor-in-Chief, the authors and John
      Wiley & Sons, Ltd. The retraction has been agreed due to errors in the data
      analysis which affect the article's findings.

PMID- 26311522
TI  - Retraction statement: Investigating factors associated with nurses' attitudes
      towards perinatal bereavement care: a study in Shandong and Hong Kong.
AB  - The above article from Journal of Clinical Nursing, 'Investigating factors
      associated with nurses' attitudes towards perinatal bereavement care: a study in
      Shandong and Hong Kong' by Chan, M. F., Lou, F.-l., Cao, F.-l., Li, P., Liu, L.
      and Wu, L. H. published online on 6 July 2009 in Wiley Online Library
      (wileyonlinelibrary.com) and in Volume 18, pp. 2344-2354, has been retracted by
      agreement between the authors, the journal Editor in Chief and John Wiley & Sons
      Ltd. The retraction has been agreed following an investigation carried out by the
      National University of Singapore due to major overlap with a previously published
      article: Chan MF, Lou F-l, Arthur DG, Cao F-l, Wu LH, Li P, Sagara-Rosemeyer M,
      Chung LYF & Lui L (2008) Investigating factors associate to nurses' attitudes
      towards perinatal bereavement care. Journal of Clinical Nursing 17: 509-518. doi:
      10.1111/j.1365-2702.2007.02007.x.

PMID- 26311523
TI  - Phylogenetic analysis of HCV subgenotypes in patients from Sichuan province in
      China based on the NS5B region.
AB  - The classification of hepatitis C virus (HCV) genotypes is of clinical importance
      as it may help to predict drug therapy responses and estimate treatment duration.
      The classical method of HCV subgenotype classification is whole genome sequencing
      (WGS). However, the high cost and time-consuming nature of WGS limits its usage
      in clinical practice. A number of studies have been conducted to confirm whether
      specific regions of HCV could replace WGS in the classification of HCV
      subgenotypes. In the present study, we used the HCV database to select HCV
      sequences from different countries. The neighbor-joining method was used to
      construct phylogenetic trees based on different regions of HCV (core, E1, E2 and
      NS5B), to confirm which region could replace WGS in subgenotype classification.
      Our results indicated that the core, E1 and E2 regions could not be used to
      classify the HCV subgenotype correctly (core failed to recognize subgenotypes c
      and a, E1 failed to discriminate between subgenotypes a and b, and E2 failed to
      identify subgenotypes a and c). The NS5B region provided the correct subgenotype
      classification. The HCV samples (n=153) collected from patients in Sichuan
      province, (Southwest China) were sequenced and classified based on the NS5B
      region. The results indicated that the major subgenotype of HCV in patients from
      Sichuan was 1b (51.6%, n=79); other subgenotypes included 3b (30.1%, n=46), 3a
      (7.8%, n=12), 6a (8.5%, n=13), 2a (n=2) and 6n (n=1). The data from our analysis
      may prove to be helpful in future epidemiological investigations of HCV, and may
      aid in the prevention and clinical treatment of HCV. 

PMID- 26311524
TI  - Redefining metamorphosis in spiny lobsters: molecular analysis of the phyllosoma
      to puerulus transition in Sagmariasus verreauxi.
AB  - The molecular understanding of crustacean metamorphosis is hindered by small
      sized individuals and inability to accurately define molt stages. We used the
      spiny lobster Sagmariasus verreauxi where the large, transparent larvae enable
      accurate tracing of the transition from a leaf-shaped phyllosoma to an
      intermediate larval-juvenile phase (puerulus). Transcriptomic analysis of larvae
      at well-defined stages prior to, during, and following this transition show that
      the phyllosoma-puerulus metamorphic transition is accompanied by vast
      transcriptomic changes exceeding 25% of the transcriptome. Notably, genes
      previously identified as regulating metamorphosis in other crustaceans do not
      fluctuate during this transition but in the later, morphologically-subtle
      puerulus-juvenile transition, indicating that the dramatic phyllosoma-puerulus
      morphological shift relies on a different, yet to be identified metamorphic
      mechanism. We examined the change in expression of domains and gene families,
      with focus on several key genes. Our research implies that the separation in
      molecular triggering systems between the phyllosoma-puerulus and puerulus
      juvenile transitions might have enabled the extension of the oceanic phase in
      spiny lobsters. Study of similar transitions, where metamorphosis is uncoupled
      from the transition into the benthic juvenile form, in other commercially
      important crustacean groups might show common features to point on the
      evolutionary advantage of this two staged regulation. 

PMID- 26311525
TI  - Exploring the role of interleukin-22 in neurological and autoimmune disorders.
AB  - Interleukin-22 (IL-22) is a member of the IL-10 cytokine family that has recently
      gained attention in regard to its recognized pathogenic role in neurological and
      autoimmune disorders. The pathological involvement of IL-22 has been linked to
      Th17 cells that are involved in its production. Its biological activity results
      from its ability to bind to a heterodimeric receptor consisting of IL-22 receptor
      1 (IL-22R1) and IL-10R2. Emerging evidence has identified IL-22 involvement in
      neurological diseases and autoimmune disorders such as Guillain-Barre Syndrome
      (GBS), multiple sclerosis (MS), Alzheimer's disease (AD), encephalitis,
      inflammatory myopathies, myasthenia gravis (MG), systemic lupus erythematosus
      (SLE), rheumatoid arthritis (RA), Sjogren's syndrome (SS), psoriasis and Crohn's
      disease (CD). However, the biological activity of IL-22 is variable resulting in
      protective or pathogenic effects in different disease states. As such, the
      development of therapeutic targeting strategies to modify the biological activity
      of IL-22 is being explored as a promising interventional approach to treat
      neurological and autoimmune diseases. 

PMID- 26311526
TI  - PATHOS: a phase II/III trial of risk-stratified, reduced intensity adjuvant
      treatment in patients undergoing transoral surgery for Human papillomavirus (HPV)
      positive oropharyngeal cancer.
AB  - BACKGROUND: Human papillomavirus-positive oropharyngeal squamous cell carcinoma
      is increasing in incidence worldwide. Current treatments are associated with high
      survival rates but often result in significant long-term toxicities. In
      particular, long-term dysphagia has a negative impact on patient quality of life
      and health. The aim of PATHOS is to determine whether reducing the intensity of
      adjuvant treatment after minimally invasive transoral surgery in this favourable
      prognosis disease will result in better long-term swallowing function whilst
      maintaining excellent disease-specific survival outcomes. METHODS/DESIGN: The
      study is a multicentre phase II/III randomised controlled trial for patients with
      biopsy-proven Human papillomavirus-positive oropharyngeal squamous cell cancer
      staged T1-T3 N0-N2b with a primary tumour that is resectable via a transoral
      approach. Following transoral surgery and neck dissection, patients are allocated
      into three groups based on pathological risk factors for recurrence. Patients in
      the low-risk pathology group will receive no adjuvant treatment, as in standard
      practice. Patients in the intermediate-risk pathology group will be randomised to
      receive either standard dose post-operative radiotherapy (control) or reduced
      dose radiotherapy. Patients in the high-risk pathology group will be randomised
      to receive either post-operative chemoradiotherapy (control) or radiotherapy
      alone. The primary outcome of the phase II study is patient reported swallowing
      function measured using the MD Anderson Dysphagia Inventory score at 12 months
      post-treatment. If the phase II study is successful, PATHOS will proceed to a
      phase III non-inferiority trial with overall survival as the primary endpoint.
      DISCUSSION: PATHOS is a prospective, randomised trial for Human papillomavirus
      positive oropharyngeal cancer, which represents a different disease entity
      compared with other head and neck cancers. The trial aims to demonstrate that
      long-term dysphagia can be lessened by reducing the intensity of adjuvant
      treatment without having a negative impact on clinical outcome. The study will
      standardise transoral surgery and post-operative intensity-modulated radiotherapy
      protocols in the UK and develop a gold-standard swallowing assessment panel. An
      associated planned translational research programme, underpinned by tumour
      specimens and sequential blood collected as part of PATHOS, will facilitate
      further empirical understanding of this new disease and its response to
      treatment. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov
      identifier NCT02215265 .

PMID- 26311527
TI  - Association between walking ability and trunk and lower-limb muscle atrophy in
      institutionalized elderly women: a longitudinal pilot study.
AB  - BACKGROUND: The aim of this study was to investigate the association between
      walking ability and muscle atrophy in the trunk and lower limbs. METHODS:
      Subjects in this longitudinal study were 21 elderly women who resided in nursing
      homes. The thicknesses of the following trunk and lower-limb muscles were
      measured using B-mode ultrasound: rectus abdominis, external oblique, internal
      oblique, transversus abdominis, erector spinae, lumbar multifidus, psoas major,
      gluteus maximus, gluteus medius, gluteus minimus, rectus femoris, vastus
      lateralis, vastus intermedius, biceps femoris, gastrocnemius, soleus, and
      tibialis anterior. Maximum walking speed was used to represent walking ability.
      Maximum walking speed and muscle thickness were assessed before and after a 12
      month period. RESULTS: Of the 17 measured muscles of the trunk and lower limbs,
      age-related muscle atrophy in elderly women was greatest in the erector spinae,
      rectus femoris, vastus lateralis, vastus intermedius, and tibialis anterior
      muscles. Correlation coefficient analyses showed that only the rate of thinning
      of the vastus lateralis was significantly associated with the rate of decline in
      maximum walking speed (r = 0.518, p < 0.05). CONCLUSIONS: This longitudinal study
      suggests that reduced walking ability may be associated with muscle atrophy in
      the trunk and lower limbs, especially in the vastus lateralis muscle, among frail
      elderly women.

PMID- 26311528
TI  - Platelet activation is less enhanced in the new balloon expandable Edwards Sapien
      3 valve compared to its predecessor model (Edwards Sapien XT).
AB  - Stroke and thromboembolic events after transfemoral aortic valve replacement
      (TAVR) continue to be a problem. The aim of our study was to compare platelet
      aggregation (Agg) and platelet activation (PA) observed with two different
      catheter valves, the ESV-XT and the newer ESV-3 valve in patients (pts)
      undergoing TAVR on dual antiplatelet therapy (DAPT). A total of 174 patients with
      severe aortic stenosis and high surgical risk successfully underwent TAVR (60 ESV
      XT; 114 ESV-3). Platelet Agg and PA (CD62P expression) were evaluated before and
      the following three days after TAVR under DAPT. Platelet Agg was inhibited to the
      same extent in both valve types and there was no significant difference in
      platelet drop between both valve types between day 0 and day 3 [ESV-XT vs ESV-3:
      median (25th-75th percentile): platelet count (x1000): 55 (42-74) vs 61(42-93),
      p=0.280]. However, there was an enhanced CD62P expression directly after TAVR
      with the ESV-XT compared to the ESV-3 [CD62P (MIF): 7.4 (6.8-8.6) vs 6.6 (6-7.9),
      p=0.014]. Surface expression of platelet CD62P was associated with the occurrence
      of residual aortic regurgitation (AR) and was significantly higher in patients
      with residual AR [CD62P (mild AR) vs CD 62P (no or trace AR): 7.9 (7.3-9.1) vs
      7.1 (6.4-8.0), p < 0.001)]. PA was significantly enhanced in patients with the
      ESV-XT compared to the ESV-3 valve and was associated with the amount of residual
      AR which was significantly reduced by ESV-3. This may have implications for
      thromboembolic events following TAVR procedure. 

PMID- 26311529
TI  - Living legend in surgery: Professor Masatoshi Makuuchi.

PMID- 26311530
TI  - High rate of microbleed formation following primary intracerebral hemorrhage.
AB  - BACKGROUND: We sought to investigate the frequency of microbleed development
      following intracerebral hemorrhage in a predominantly African-American population
      and to identify predictors of new microbleed formation. AIMS AND/OR HYPOTHESIS:
      To investigate the frequency and predictors of new microbleeds following
      intracerebral hemorrhage. METHODS: The DECIPHER study was a prospective,
      longitudinal, magnetic resonance-based cohort study designed to evaluate
      racial/ethnic differences in risk factors for microbleeds and to evaluate the
      prognostic impact of microbleeds in this intracerebral hemorrhage population. We
      evaluated new microbleed formation in two time periods: from baseline to 30 days
      and from 30 days to year 1. RESULTS: Of 200 subjects enrolled in DECIPHER, 84 had
      magnetic resonance imaging at all required time points to meet criteria for this
      analysis. In the baseline to day 30 analysis, 11 (13.1%) had new microbleeds,
      compared with 25 (29.8%) in the day 30 to year 1 analysis. Logistic regression
      analysis demonstrated that baseline number of microbleeds [odds ratio 1.05 (95%
      confidence interval 1.01, 1.08), P = 0.01] was associated with new microbleed
      formation at 30 days. A logistic regression model predicting new microbleed at
      one-year included baseline number of microbleeds [odds ratio 1.05 (1.00, 1.11), P
      = 0.046], baseline age [odds ratio 1.05 (1.00, 1.10), P = 0.04], and white matter
      disease score [odds ratio 1.18 (0.96, 1.45). P = 0.115]. Overall, 28 of 84
      (33.3%) intracerebral hemorrhage subjects formed new microbleeds at some point in
      the first year post-intracerebral hemorrhage. CONCLUSIONS: We found that one
      third of intracerebral hemorrhage subjects in this cohort surviving one-year
      developed new microbleeds, which suggests a dynamic and rapidly progressive
      vasculopathy. Future studies are needed to examine the impact of new microbleed
      formation on patient outcomes.

PMID- 26311532
TI  - Multi-spectroscopic and molecular modeling investigation of the interactions
      between prantschimgin and matrix metalloproteinase 9 (MMP9).
AB  - The binding of prantschimgin (PRAN) to matrix metalloproteinase 9 (MMP9) was
      investigated using multiple techniques. Fluorescence spectroscopy showed that
      PRAN could quench the MMP9 fluorescence spectra. Changes in the UV/vis and
      Fourier transform infrared (FTIR) spectra were observed upon ligand binding,
      along with a significant degree of tryptophan fluorescence quenching on complex
      formation. The interaction of PRAN with MMP9 has also been studied using
      molecular docking and molecular dynamics (MD) simulation. The binding models
      demonstrated aspects of PRAN's conformation, active site interaction, important
      amino acids and hydrogen bonding. Computational mapping of the possible binding
      site of PRAN revealed that the ligand is bound in a large hydrophobic cavity of
      MMP9. The MD simulation results suggested that this ligand can interact with the
      protein, with little affecting the secondary structure. The results not only lead
      to a better understanding of interactions between PRAN and MMP9, but also provide
      useful data about the influence of PRAN on the structural conformation. The data
      provided in this study will be useful for designing a new agonist of MMP9 with
      the desired activity.

PMID- 26311531
TI  - Application of a BOSS-Gaussian interface for QM/MM simulations of Henry and
      methyl transfer reactions.
AB  - Hybrid quantum mechanics and molecular mechanics (QM/MM) computer simulations
      have become an indispensable tool for studying chemical and biological phenomena
      for systems too large to treat with QM alone. For several decades, semiempirical
      QM methods have been used in QM/MM simulations. However, with increased
      computational resources, the introduction of ab initio and density function
      methods into on-the-fly QM/MM simulations is being increasingly preferred. This
      adaptation can be accomplished with a program interface that tethers independent
      QM and MM software packages. This report introduces such an interface for the
      BOSS and Gaussian programs, featuring modification of BOSS to request QM energies
      and partial atomic charges from Gaussian. A customizable C-shell linker script
      facilitates the interprogram communication. The BOSS-Gaussian interface also
      provides convenient access to Charge Model 5 (CM5) partial atomic charges for
      multiple purposes including QM/MM studies of reactions. In this report, the BOSS
      Gaussian interface is applied to a nitroaldol (Henry) reaction and two methyl
      transfer reactions in aqueous solution. Improved agreement with experiment is
      found by determining free-energy surfaces with MP2/CM5 QM/MM simulations than
      previously reported investigations using semiempirical methods.

PMID- 26311533
TI  - HSS revisited: multi-channel processes mediate trophic control across a
      productivity gradient.
AB  - Classical food web theory holds that energy channels are regulated by top-down
      control with increasing productivity, arising from within-channel processes.
      However, these hypotheses do not consider the existence of parallel energy
      channels linked by shared resource pools and which can fuel generalist predators,
      imposing trophic control arising from multi-channel processes. Using 23 large
      marine food webs, we show that food web responses to increasing productivity are
      consistent with the apparent trophic cascade hypothesis (ATCH) - with rising
      productivity predators derive an increasing fraction of their diet from
      increasingly productive bottom-up controlled detritus channels, thereby
      subsidising predator biomass, and in turn strengthening top-down control in
      parallel grazing channels. These results testify to a fundamental role of
      detritus channels specifically and multi-channel processes in general in
      mediating food web response to productivity and demonstrate that the ATCH
      provides an alternative explanation for classical predictions of top-down
      control.

PMID- 26311534
TI  - Ethnic enclaves and risk of psychiatric disorders among first- and second
      generation immigrants in Sweden.
AB  - PURPOSE: Some non-Western immigrant groups in Europe have elevated risk of
      psychosis relative to native-born. It is hypothesized that neighborhood ethnic
      density moderates this risk. Immigration to Sweden has increased substantially
      recently, particularly from the Middle East. This study examined the relationship
      between neighborhood ethnic density (i.e., living in an immigrant enclave) and
      risk of psychotic and affective disorders among three groups: Iraqi immigrants,
      immigrants from other nations, and native-born Swedes. METHODS: Individuals aged
      15-60, without prevalent psychopathology, were drawn from Swedish population
      based registries and followed from 2005 to 2010 (N = 950,979). Multi-level
      logistic regression was used to examine the association between neighborhood
      ethnic composition and incident psychopathology. RESULTS: Cumulative incidence of
      psychopathology was greater in Iraqi enclaves relative to predominantly Swedish
      neighborhoods (6.3 vs. 4.5%). Iraqis living in enclaves did not have
      significantly greater risk of psychosis (Odds Ratio (OR): 1.66, 95% Confidence
      Interval (CI) 0.92-2.97) or affective disorders (OR: 1.04, 95%CI 0.85-1.27)
      relative to those in predominantly Swedish neighborhoods. There was no increased
      risk of psychosis (OR: 0.93, p > 0.05) or affective disorders (OR: 0.93, p >
      0.05) for other immigrants living in an enclave. Swedes living in an enclave had
      elevated risk of both psychosis (OR: 1.37, p < 0.05) and affective disorders (OR:
      1.14, p < 0.05) relative to those in predominantly Swedish neighborhoods. Second
      generation Iraqis had higher risk of psychotic but not affective disorders
      relative to first-generation. CONCLUSIONS: Neighborhood ethnic density does not
      moderate risk of psychopathology for immigrants in Sweden. Findings regarding
      Swedes are consistent with social drift.

PMID- 26311536
TI  - Actinoplanes luteus sp. nov., isolated from soil.
AB  - A novel filamentous bacterial strain, A-T 5190T, which developed irregular
      sporangia at the end of sporangiophores on substrate mycelia, was isolated from
      dry evergreen forest soil collected in Thailand. The 16S rRNA gene sequence and
      phylogenetic analysis indicated that strain A-T 5190T belonged to the genus
      Actinoplanes and was related most closely to Actinoplanes palleronii NBRC 14916T
      (98.88 % similarity) and Actinoplanes rectilineatus NBRC 13941T (98.54 %). DNA
      DNA relatedness values between strain A-T 5190T and its closest relatives were
      below 70 %. The cell-wall peptidoglycan contained meso-diaminopimelic acid. The
      whole-cell sugars contained rhamnose, ribose, galactose and xylose. The
      predominant menaquinone was MK-9(H4). The diagnostic phospholipids were
      phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol and
      phosphatidylinositol. The predominant cellular fatty acids were unsaturated fatty
      acid C17 : 1 and branched fatty acids iso-C16 : 0, iso-C15 : 0 and anteiso-C17 :
      0. The G+C content of the genomic DNA was 71.9 mol%. Evidence from phenotypic,
      chemotaxonomic and genotypic studies indicate that strain A-T 5190T represents a
      novel species of the genus Actinoplanes, for which the name Actinoplanes luteus
      sp. nov. is proposed. The type strain is A-T 5190T ( = BCC 41582T = NBRC
      109644T).

PMID- 26311535
TI  - Structural analysis of fungus-derived FAD glucose dehydrogenase.
AB  - We report the first three-dimensional structure of fungus-derived glucose
      dehydrogenase using flavin adenine dinucleotide (FAD) as the cofactor. This is
      currently the most advanced and popular enzyme used in glucose sensor strips
      manufactured for glycemic control by diabetic patients. We prepared recombinant
      nonglycosylated FAD-dependent glucose dehydrogenase (FADGDH) derived from
      Aspergillus flavus (AfGDH) and obtained the X-ray structures of the binary
      complex of enzyme and reduced FAD at a resolution of 1.78 A and the ternary
      complex with reduced FAD and D-glucono-1,5-lactone (LGC) at a resolution of 1.57
      A. The overall structure is similar to that of fungal glucose oxidases (GOxs)
      reported till date. The ternary complex with reduced FAD and LGC revealed the
      residues recognizing the substrate. His505 and His548 were subjected for site
      directed mutagenesis studies, and these two residues were revealed to form the
      catalytic pair, as those conserved in GOxs. The absence of residues that
      recognize the sixth hydroxyl group of the glucose of AfGDH, and the presence of
      significant cavity around the active site may account for this enzyme activity
      toward xylose. The structural information will contribute to the further
      engineering of FADGDH for use in more reliable and economical biosensing
      technology for diabetes management. 

PMID- 26311537
TI  - Gestational age at initial exposure to in utero inflammation influences the
      extent of diaphragm dysfunction in preterm lambs.
AB  - BACKGROUND AND OBJECTIVE: In utero infection may critically influence diaphragm
      development and predispose preterm infants to postnatal respiratory failure. We
      aimed to determine how frequency and gestational age (GA) at time of intra
      amniotic (IA) lipopolysaccharide (LPS) exposure affects preterm diaphragm
      function. METHODS: Pregnant ewes received IA injections of saline or 10-mg LPS at
      7 days or 21 days or weekly injections 21, 14 and 7 days before delivery at 121
      day GA. Foetal lambs were killed with pentobarbitone (150 mg/kg; intravenous).
      Diaphragm contractile function was measured in vitro. Muscle fibre type,
      activation of protein synthesis and degradation pathways, pro-inflammatory
      signalling and oxidative stress were evaluated using immunofluorescence staining,
      RT-qPCR, ELISA, Western blotting and biochemical assay. RESULTS: In utero LPS
      exposure significantly impaired diaphragm contractile function. LPS exposure 7
      days before delivery caused maximum specific twitch and tetanic forces 30% lower
      than controls. When the initial LPS exposure occurred 21 days before delivery
      maximum specific forces were 40% lower than controls. Earlier LPS exposure also
      prolonged twitch contraction time, increased fatigue resistance and elevated
      protein carbonyl content. Despite increased white blood cell counts and
      interleukin-6 mRNA expression following weekly LPS exposure, there were no
      significant differences in contractile properties between exposure 21 days before
      delivery and repeated LPS groups suggesting that frequency of inflammatory
      exposure does not influence the severity of contractile dysfunction. CONCLUSIONS:
      GA at time of initial LPS exposure, rather than frequency of exposure, determines
      the extent of inflammation-induced diaphragm dysfunction.

PMID- 26311538
TI  - Depression and stress amongst undergraduate medical students.
AB  - BACKGROUND: The demands placed on medical trainees pose a challenge to personal
      wellbeing, leading to burnout and erosion of empathy. However, it is unclear at
      what point in medical education this decline begins. Although many schools have
      begun to design and implement wellness programs for their students, the medical
      education community's experience in evaluating their impact is limited. METHODS:
      The authors designed a wellness needs assessment of all medical students at the
      Albert Einstein College of Medicine in order to assess students' health
      behaviors, stress and depressive symptoms. The online survey was administered to
      all medical students from the classes of 2014 and 2015 at the beginning of their
      first year of medical school and again at the end of their third year. Chi-square
      and T-tests were run comparing the survey responses of the two classes. RESULTS:
      There was a significant increase in perceived stress from an average of 5.51 in
      the first year to 6.49 in the third year (p = .0001). The number of students at
      risk for depression, defined as a CES-D score greater than 16, was 94 (28.4%) in
      the first year and 131 (39.0%) in their third year (p = .004). CONCLUSIONS: This
      study demonstrates a significant increase in the proportion of students at risk
      for depression in their third year as compared to the first year as well as an
      increase in perceived stress. In response to these findings, the authors took a
      multi-disciplinary approach in the development of a comprehensive program to
      address student wellness, including efforts to address issues specific to the
      clinical clerkships. This program is unique in that its design, inception and
      ongoing evaluation have taken the needs of an entire medical school class into
      account.

PMID- 26311539
TI  - The impact of next-generation sequencing technologies on HLA research.
AB  - In the past decade, the development of next-generation sequencing (NGS) has paved
      the way for whole-genome analysis in individuals. Research on the human leukocyte
      antigen (HLA), an extensively studied molecule involved in immunity, has
      benefitted from NGS technologies. The HLA region, a 3.6-Mb segment of the human
      genome at 6p21, has been associated with more than 100 different diseases,
      primarily autoimmune diseases. Recently, the HLA region has received much
      attention because severe adverse effects of various drugs are associated with
      particular HLA alleles. Owing to the complex nature of the HLA genes, classical
      direct sequencing methods cannot comprehensively elucidate the genomic makeup of
      HLA genes. Thus far, several high-throughput HLA-typing methods using NGS have
      been developed. In HLA research, NGS facilitates complete HLA sequencing and is
      expected to improve our understanding of the mechanisms through which HLA genes
      are modulated, including transcription, regulation of gene expression and
      epigenetics. Most importantly, NGS may also permit the analysis of HLA-omics. In
      this review, we summarize the impact of NGS on HLA research, with a focus on the
      potential for clinical applications. 

PMID- 26311540
TI  - Joint effect of the SMN2 and SERF1A genes on childhood-onset types of spinal
      muscular atrophy in Serbian patients.
AB  - Spinal muscular atrophy (SMA) is caused by functional loss of the survival of
      motor neuron 1 (SMN1) gene. Despite genetic homogeneity, phenotypic variability
      indicates the involvement of disease modifiers. SMN1 is located in 5q13.2
      segmental duplication, enriched in genes and prone to unequal rearrangements,
      which results in copy number polymorphism (CNP). We examined the influence of CNP
      of 5q13.2 genes and their joint effect on childhood-onset SMA phenotype.
      Multiplex ligation-dependent probe amplification (MLPA) was used to construct
      5q13.2 alleles and assess copy number of the SMN2, small EDRK-rich factor 1A
      (SERF1A) and NLR family apoptosis inhibitory protein (NAIP) genes in 99 Serbian
      patients with SMN1 homozygous absence (23-type I, 37-type II and 39-mild type
      III) and 122 patients' parents. Spearman rank test was performed to test
      correlation of individual genes and SMA type. Generalized linear models and
      backward selection were performed to obtain a model explaining phenotypic
      variation with the smallest set of variables. 5q13.2 alleles most commonly
      associated with type I harbored large-scale deletions, while those detected in
      types II and III originated from conversion of SMN1 to SMN2. Inverse correlation
      was observed between SMN2, SERF1A and NAIP CNP and SMA type (P=2.2e-16, P=4.264e
      10, P=2.722e-8, respectively). The best minimal model describing phenotypic
      variability included SMN2 (P<2e-16), SERF1A (P<2e-16) and their interaction
      (P=0.02628). SMN2 and SERF1A have a joint modifying effect on childhood-onset SMA
      phenotype. 

PMID- 26311541
TI  - Setleis syndrome due to inheritance of the 1p36.22p36.21 duplication: evidence
      for lack of penetrance.
AB  - Setleis syndrome, focal facial dermal dysplasia type III (FFDD3, MIM #227260), is
      characterized by scar-like bitemporal lesions and other ocular and facial
      dysmorphic features. The syndrome results from recessive mutations in the TWIST2
      gene, encoding a basic helix-loop-helix transcription factor or de novo genomic
      duplication or triplication, which include 1.3 Mb at 1p36.22p36.21, or other yet
      undefined lesions, emphasizing the syndrome's genetic heterogeneity. Recently,
      three patients were reported with 1p36.22p36.21 duplications/triplication that
      had the characteristic FFDD3 features and developmental delay or intellectual
      disabilities. Here, we describe a male with this microduplication, and the
      typical FFDD3 phenotype, but normal intelligence. Notably, his duplication was
      inherited from his father who did not have any FFDD3 manifestations, indicating
      lack of penetrance of the 1p36.22p36.21 microduplication. These findings
      emphasize phenotypic heterogeneity of the 1p36.22p36.21 copy number variant and
      the importance of screening the parents of patients with the 1p36.22p36.21 copy
      number variant to determine whether the duplication/triplication is de novo or
      inherited, for informed reproductive and genetic counseling. 

PMID- 26311542
TI  - Haemophilus influenzae: using comparative genomics to accurately identify a
      highly recombinogenic human pathogen.
AB  - BACKGROUND: Haemophilus influenzae is an opportunistic bacterial pathogen that
      exclusively colonises humans and is associated with both acute and chronic
      disease. Despite its clinical significance, accurate identification of H.
      influenzae is a non-trivial endeavour. H. haemolyticus can be misidentified as H.
      influenzae from clinical specimens using selective culturing methods, reflecting
      both the shared environmental niche and phenotypic similarities of these species.
      On the molecular level, frequent genetic exchange amongst Haemophilus spp. has
      confounded accurate identification of H. influenzae, leading to both false
      positive and false-negative results with existing speciation assays. RESULTS:
      Whole-genome single-nucleotide polymorphism data from 246 closely related global
      Haemophilus isolates, including 107 Australian isolate genomes generated in this
      study, were used to construct a whole-genome phylogeny. Based on this phylogeny,
      H. influenzae could be differentiated from closely related species. Next, a H.
      influenzae-specific locus, fucP, was identified, and a novel TaqMan real-time PCR
      assay targeting fucP was designed. PCR specificity screening across a panel of
      clinically relevant species, coupled with in silico analysis of all species
      within the order Pasteurellales, demonstrated that the fucP assay was 100 %
      specific for H. influenzae; all other examined species failed to amplify.
      CONCLUSIONS: This study is the first of its kind to use large-scale comparative
      genomic analysis of Haemophilus spp. to accurately delineate H. influenzae and to
      identify a species-specific molecular signature for this species. The fucP assay
      outperforms existing H. influenzae targets, most of which were identified prior
      to the next-generation genomics era and thus lack validation across a large
      number of Haemophilus spp. We recommend use of the fucP assay in clinical and
      research laboratories for the most accurate detection and diagnosis of H.
      influenzae infection and colonisation.

PMID- 26311544
TI  - Development of a Rhodium(II)-Catalyzed Chemoselective C(sp(3) )-H Oxygenation.
AB  - We report the first example of Rh(II) -catalyzed chemoselective double C(sp(3) )
      H oxygenation, which can directly transform various toluene derivatives into
      highly valuable aromatic aldehydes with great chemoselectivity and practicality.
      The critical combination of catalyst Rh(OAc)2 , oxidant Selectfluor, and solvents
      of TFA/TFAA promises the successful delivery of the oxidation with satisfactory
      yields. A possible mechanism involving a unique carbene-Rh complex is proposed,
      and has been supported by both experiments and theoretical calculations.

PMID- 26311543
TI  - Medicare Utilization and Expenditures Around Incident Dementia in a Multiethnic
      Cohort.
AB  - BACKGROUND: Few studies have examined patterns of health care utilization and
      costs during the period around incident dementia. METHODS: Participants were
      drawn from the Washington Heights-Inwood Columbia Aging Project, a multiethnic,
      population-based, prospective study of cognitive aging of Medicare beneficiaries
      in a geographically defined area of northern Manhattan. Medicare utilization and
      expenditure were examined in individuals with clinically diagnosed dementia from
      2 years before until 2 years after the initial diagnosis. A sample of non
      demented individuals who were matched on socio-demographic and clinical
      characteristics at study enrollment was used as controls. Multivariable
      regression analysis estimated effects on Medicare utilization and expenditures
      associated with incident dementia. RESULTS: During the 2 years before incident
      dementia, rates of inpatient admissions and outpatient visits were similar
      between dementia patients and non-demented controls, but use of home health and
      skilled nursing care and durable medical equipment were already higher in
      dementia patients. Results showed a small but significant excess increase
      associated with incident dementia in inpatient admissions but not in other areas
      of care. In the 2 years before incident dementia, total Medicare expenditures
      were already higher in dementia patients than in non-demented controls. But we
      found no excess increases in Medicare expenditures associated with incident
      dementia. CONCLUSIONS: Demand for medical care already is increasing and costs
      are higher at the time of incident dementia. There was a small but significant
      excess risk of inpatient admission associated with incident dementia.

PMID- 26311545
TI  - [Consensus on prevention of adhesions for the obstetric and gynecologic surgery:
      Chinese experts' opinion (version 2015)].

PMID- 26311546
TI  - [Attention to some problems of pelvic floor reconstruction surgery in pelvic
      organ prolapse].

PMID- 26311547
TI  - [Efficiency of single incision adjustable mini sling, Ajust, for the treatment of
      stress urinary incontinence combined with advanced pelvic organ prolapse in eldly
      women].
AB  - OBJECTIVE: To estimate the efficiency of the single incision adjustable mini
      sling, Ajust, in the treatment of stress urinary incontinence (SUI) concomitant
      with advanced pelvic organ prolapse (POP) in eldly women. METHODS: From Dec. 2013
      to Jul. 2014, 58 patients who had been diagnosed as SUI combined with advanced
      POP underwent both single incision adjustable mini sling and reductive surgery
      for advanced POP in the First Affiliated Hospital, General Hospital of People's
      Liberation Army. Fifty-eight patients were assessed to evaluate the safety and
      efficiency at 2, 6, 12 months postoperatively. The primary outcomes include
      objective and subjective cure rate, Ajust sling related complications, ralues of
      urinary distress inventory (UDI-6), incontinence impact questionnaire short form
      (IIQ-7) and patient global impression of change (PGI-C). RESULTS: There was no
      case of leakage tested by cough test, so the objective cure rate for anti
      incontinence had been achived to 100% (58/58) at a mean 12 months follow-up.
      There were 91% (53/58) of the patients' PGI-C score reached 5, and 9% (5/58) of
      the patients' PGI-C score reached 4. No case underwent the reoperation. There was
      no case of hematoma, bladder perforation, urethral injury, groin pain, as well as
      pain in the puncture point during the perioperative period of time. The values of
      UDI-6 and IIQ-7 declined significantly postoperatively (P < 0.01). CONCLUSIONS:
      The single incision mini sling, Ajust, presents satisfactory objective and
      subjective cure rate in the treatment of mild and moderate SUI combined with
      severe POP in the eldly womem. The advantages of this mini sling includes mini
      invasiveness, simple to use, rare complications and less urinary retention rate.
      It is a procedure worth recommending in the clinical treatment of mild to
      moderate SUI.

PMID- 26311548
TI  - [POP-Q indication points, Aa and Ba, involve in diagnosis and prognosis of occult
      stress urinary incontinence complicated with pelvic organ prolapse].
AB  - OBJECTIVE: To investigate the correlation between pelvic organ prolapse
      quantitation (POP-Q) indication points and the incidence of occult stress urinary
      incontinence (OSUI) and its impact on prognosis. METHODS: Retrospective study
      medical records of 93 patients with pelvic organ prolapse (POP) staged at III-IV,
      of which underwent pelvic reconstruction operations with Prolift system from Jan.
      2007 to Sept. 2012. None of these patients had clinical manifestations of stress
      urinary incontinence (SUI) before surgery, and in which 44 patients were included
      in study group (POP complicated with OSUI) because they were identified with
      OSUI, another 49 patients as control group (simple POP). Follow-up and collecting
      datas including POP-Q, stress test, urodynamic recordings, incidence of de novo
      SUI, statistic analyzing by logistic regression and receiver operating
      characteristic curve (ROC). RESULTS: (1) The study group had a much higher
      incidence of 30% (13/44) on de novo SUI than that of control group (4%, 2/49; P <
      0.01). (2) Vaginal delivery (OR = 5.327, 95% CI: 1.120-25.347), constipation (OR
      = 5.789, 95% CI: 1.492-22.459), preoperative OSUI (OR = 13.695, 95% CI: 2.980
      62.944), anterior vaginal wall prolapse (OR = 6.115, 95% CI: 1.231-30.379) were
      identified as dependent risk factors for de novo SUI by logistic regression
      analysis. (3) For POP patients that complicated with OSUI, we chose a cutoff
      value of +1.5 cm for Aa point as the threshold to predicting incidence of de novo
      SUI according to ROC curve, area under the curve (AUC) was 0.889 (P < 0.05), the
      sensitivity reached 88.9% and specificity was 73.9%. According to ROC curve of Ba
      point, a cutoff value of +2.5 cm was chosen as the threshold to predicting
      incidence of de novo SUI post-operation, it had a sensitivity of 66.7% and
      specificity of 82.6%, AUC was 0.766 (P < 0.05). CONCLUSIONS: Pre-operative OSUI
      is a dependent risk factor of de novo SUI for advanced POP patients. Aa and Ba
      points are correlated with preoperative OSUI, and it is worthy to be considered
      as a risk predictor on forecasting the incidence of de novo SUI post pelvic
      reconstruction surgery.

PMID- 26311549
TI  - [Postpartum pelvic floor rehabilitation on prevention of female pelvic floor
      dysfunction: a multicenter prospective randomized controlled study].
AB  - OBJECTIVE: To study the postpartum pelvic floor rehabilitation on the improvement
      of pelvic floor electrical physiological indexes and the prevention of female
      pelvic floor dysfunction in China. METHODS: A multicenter prospective randomized
      controlled study was carried out. From October 2011, postpartum women in five
      provinces were randomly assigned into treatment group and control group. The
      women in treatment group received electrical stimulation and biofeedback
      treatment. The women in control group performed pelvic floor muscle exercise at
      home. When 6 months and 12 months after delivery, comparing two groups of
      patients with pelvic floor electrical physiological indexes and pelvic organ
      prolapse quantitation measurements (POP-Q), to evaluate the effect of postpartum
      pelvic floor rehabilitation on the prevention of pelvic floor dysfunction. Pelvic
      floor impact questionnaire short form (PFIQ-7) and pelvic organ
      prolapse/incontinence sexual questionnaire-12 (PISQ-12) were used to evaluate the
      influence on quality of life and sexual life. RESULTS: Until June 2013, 324 women
      were participated, 124 in control group, 200 in treatment group. According to the
      baseline results, there was statistical significance in the results of pelvic
      floor electrical physiological indexes between the treatment and control groups
      in postpartum 6 months and 12 months; the proportion above level III of type I
      and type II muscle fibers strength in the treatment group, it was from 41.5%
      (83/200) and 40.5% (81/200) to 76.3% (145/190) and 79.5% (151/190) in postpartum
      6 weeks and postpartum 6 months, increased to 80.6% (58/72) and 80.6% (58/72) in
      postpartum 12 months, improved significantly comparing with the control group (P
      < 0.01). According to Point Aa, treatment group and control group in the
      postpartum 6 weeks was (-2.2 +/- 0.7) versus (-2.4 +/- 0.6) cm, in postpartum 12
      months (- 2.5 +/- 1.1) versus (- 2.7 +/- 0.6) cm, the improvement in treatment
      group was statistically significant (P < 0.01). And the other points were not
      significantly different (P > 0.05). There was no significant difference in the
      questionnaires in quality of life and quality of sexual life (P > 0.05).
      CONCLUSION: Neuromuscular electrical stimulation and biofeedback therapy in the
      early postpartum period could obviously improve pelvic floor electrical
      physiological indexes, and is beneficial to prevent the pelvic floor dysfunction.

PMID- 26311550
TI  - [Comparison of levator ani muscles in three-dimensional MRI-based models in women
      with and without pelvic organ prolapse at rest].
AB  - OBJECTIVE: Comparison of the levator ani muscles in three-dimensional (3D) MRI
      based models in women with and without pelvic organ prolapse at rest to analyze
      the morphological characteristics of levator ani muscles in women with POP.
      METHODS: Twenty-five women with POP and 22 women with normal pelvic support were
      selected from Nanfang Hospital of Southern Medical University. Axial, sagittal,
      and coronal T2-weighted pelvic magnetic resonance scans were obtained with the
      women in the supine position.The 3D models were reconstructed from the source
      images. Morphological changes was compared within the two groups of levator ani
      muscles, and the 3D models were measured to determine the levator ani muscle
      volume (LVOL), levator plate angle (LPA), levator hiatus width (LH-W) and length
      (LH-L), distance between symphysis and levator sling muscle (LSG). RESULTS: There
      were no puborectalis avulsions in control, in POP, 3 cases of avulsions just in
      left, 3 cases of avulsions just in right, 7 cases in bilateral. The shape of
      iliococcygeus were all dome-shaped in control, 11 cases were U-shaped and 14
      cases were dome-shaped in POP. The shape of levator hiatus were 7 cases of U
      shape, 12 cases of V-shape, 3 cases of irregular in control; 5 cases of U-shape,
      4 cases of V-shape, 16 cases of irregular in POP. POP versus control: LH-L: (68.0
      +/- 8.9) versus (61.6 +/- 7.2) mm (P < 0.05); LH-W: (41.4 +/- 3.9) versus (38.0
      +/- 3.2) mm (P < 0.05); LSG-L: (29.6 +/- 7.4) versus (24.6 +/- 3.7) mm (P <
      0.05); LSG-R: (28.4 +/- 6.8) versus (23.9 +/- 3.2) mm (P < 0.05); LPA: (51.0 +/-
      11.3) degrees  versus (40.6 +/- 6.3) degrees  (P < 0.05); LVOL: (23.7 +/- 5.8)
      versus (24.6 +/- 5.0) cm3 (P > 0.05). CONCLUSIONS: It is possible to assess the
      morphologic changes of levator ani by using 3D MRI models objectively, our 3D
      data demonstrate larger in LVOL, LPA, LH-W, LH-L, LSG, and the changes in shape.
      It is helpful to diagnose and assess the specific situation of patients POP in
      clinic.

PMID- 26311551
TI  - [Comparison of the effect of three beta-thalassemia prenatal screening strategies
      using in Guangdong province].
AB  - OBJECTIVE: To compare the effect of three beta-thalassemia prenatal screening
      strategies in Guangdong province. METHODS: A total of 13 284 hospital-delivered
      couples and 13 369 newborns were recruited from 91 hospitals in 21 counties or
      districts of Guangdong province from June to December 2012. Mean cell volume
      (MCV), mean corpuscular hemoglobin (MCH) and hemoglobin A2 (Hb A2) were tested
      for all the couples, and all the couples and newborns were detected by 17 types
      of beta-globin gene mutations. The effect of three beta-thalassemia prenatal
      screening strategies were compared as following: (1) MCV/MCH with Hb A2 serial
      screening (SS): Hb A2 was tested if the woman's MCV < 82 fl and (or) MCH < 27 pg.
      If the woman's Hb A2 > 3.5, it meant positive. And if the woman was beta
      thalassemia carrier and her husband's Hb A2 > 3.5, it meant couple positive. (2)
      MCV/MCH with Hb A2 parallel screening (PS): if the woman's MCV < 82 fl and (or)
      MCH < 27 pg and (or) Hb A2 > 3.5 pg, it meant couple positive. And the husband
      would be tested for beta-globin gene mutations if the woman was beta-thalassemia
      carrier. (3) MCV/MCH with Hb A2 serial screening for couples (SSC): if one of the
      couple or both of them had MCV < 82 fl and (or) MCH < 27 pg, the couple would be
      tested for Hb A2, and if one of the couple got Hb A2 > 3.5, it meant couple
      positive. RESULTS: (1) For the SS strategy, the sensitivity was 92.69% (583/629);
      the specificity was 99.87% (12 638/12 655); the positive predictive value was
      97.17% (583/600); and the negative predictive value was 99.64% (12 638/12 684).
      The results of beta-globin gene mutations tested showed that the rate of beta
      thalassemia carriers was 4.74% (629/13 284) in the 13 284 pregnant women, and it
      was 4.29% (570/13 284) in their husbands. (2) The SS strategy detected 27 (0.20%,
      27/13 284) beta-thalassemia carrier couples. For the SS strategy detecting beta
      thalassemia carrier couples, the missed diagnosis rate was 11.11% (3/27); the
      sensitivity was 88.89% (24/27); the specificity was 100.00% (27/27); the positive
      predictive value was 100.00% (24/24); and the negative predictive value was
      99.98% (13 257/13 260). (3) When using the SS strategy for 13 369 offsprings,
      there were 582 beta-thalassemia carriers (4.35%, 582/13369), including 578
      (99.31%, 578/582) minor beta-thalassemia, 3 (0.52%, 3/582) intermedia beta
      thalassemia and 1 (0.17%, 1/582) major beta-thalassemia. The SS strategy detected
      25 fetuses who needed beta-thalassemia prenatal diagnosis. (4) For the PS
      strategy, the sensitivity was 98.09% (617/629); the specificity was 88.73% (11
      229/12 655); the positive predictive value was 30.20% (617/2 043); and the
      negative predictive value was 99.89% (11 229/11 241). (5) When using the PS
      strategy for the beta-thalassemia carrier couples, the sensitivity was 100.00%
      (27/27); the specificity was 95.55% (12 667/13 257); the positive predictive
      value was 4.38% (27/617); and the negative predictive value was 100.0% (12 667/12
      667). (6) The PS strategy detected 28 fetuses who needed beta-thalassemia
      prenatal diagnosis in 13 369 offsprings. (7) For the SSC strategy, the
      sensitivity was 93.80% (590/629); the specificity was 95.75% (12 117/12 655); the
      positive predictive value was 52.30% (590/1 128); and the negative predictive
      value was 99.68% (12 117/12 156). When the SSC strategy was used for the
      husbands, the sensitivity was 92.28% (526/570); the specificity was 95.27% (12
      112/12 714);the positive predictive value was 46.63% (526/1 128); and the
      negative predictive value was 99.64% (12 112/12 156). (8) When the SSC strategy
      was used in beta-thalassemia carrier couples, the sensitivity was 100.00%
      (27/27); the specificity was 91.69% (12 156/13 257); the positive predictive
      value was 2.39% (27/1 128); and the negative predictive value was 100.00% (12
      156/12 156). (9) The SSC strategy detected 28 fetuses who needed beta-thalassemia
      prenatal diagnosis. CONCLUSIONS: All the three beta-thalassemia prenatal
      screening strategies had good effect in clinical practice and public health.
      While in the high-prone area of beta-thalassemia, MCV/MCH with Hb A2 parallel
      screening and MCV/MCH with Hb A2 serial screening for couples stratigies were
      better.

PMID- 26311552
TI  - [Expression of Gas6 in placenta and decidua tissues and its relationship with the
      pathogenesis of preeclampsia].
AB  - OBJECTIVE: To investigate the expression of growth arrest-specific protein 6
      (Gas6) in the placenta and decidua tissues and its relationship with the
      pathogenesis of preeclampsia. METHODS: All the patients were recruited in Qilu
      Hospital of Shangdong University from October 2013 to June 2014. Among them,
      thirty-two women with early-onset severe preeclampsia who received cesarean
      section were assigned to the preeclampsia group, and thirty healthy pregnant
      women who received cesarean section were defined as the control group. Blood
      glucose, blood lipids, platelet count, D-dimer levels and other clinical
      indicators of the two groups were detected. Immunohistochemistry of SP was
      conducted to identify the localization of Gas6 protein in the placenta and
      decidua tissues. And reverse transcription (RT)-PCR was performed for
      quantitative analysis of Gas6 RNA expression in placentas. The correlations
      between placental Gas6 mRNA levels with clinical indicators were analyzed.
      RESULTS: (1) The gestational age at delivery, blood pressure, serum albumin,
      platelet count and birth weight of fetuses showed statistically significant
      differences between the two groups (P < 0.05). (2) The Gas6 protein expressed in
      the cytoplasm and nucleus of the syncytiotrophoblasts and decidual cells in the
      placenta and decidual tissues of the two groups. (3) The Gas6 mRNA expression
      elevated significantly in the placenta of preeclampsia group (0.60 +/- 0.38) when
      compared to that of the control group (0.34 +/- 0.22; P < 0.05). (4) The
      expression of Gas6 mRNA was positively related with body mass index, diastolic
      blood pressure, systolic blood pressure, free fatty acids and creatinine (P <
      0.05), while it was negatively associated with serum albumin (P < 0.05).
      CONCLUSION: The high expression of Gas6 in the placenta and decidua tissues may
      be related to the pathogenesis of severe preeclampsia.

PMID- 26311553
TI  - [Significance of circadian gene Period2 expression in epithelial ovarian cancer
      and the effect of gene overexpression on growth of ovarian cancer xenografts in
      nude mice].
AB  - OBJECTIVE: To study the significance of circadian gene Period2 expression in
      epithelial ovarian cancer tissues and the effect of gene overexpression on the
      growth of ovarian cancer xenografts in nude mice. METHODS: Twenty-two cases of
      ovarian cancer paraffin specimens in the First Hospital of Shanxi Medical
      University (ovarian cancer group) were chosed during Jau. 2010 to Dec. 2013,
      including 8 cases of stage I, 8 cases of stage II, and 6 cases of stage III,
      while 6 cases of benign ovarian epithelial tumor paraffin specimens were selected
      as control (benign tumor group). Period2 gene were detected by real-time
      quantitative PCR and western blot methods in different stages of ovarian cancer
      tumor tissues. Established the ovarian cancer xenografts in nude mice with
      ovarian cancer cell line SKOV3, and they were divided into 3 groups (n = 8),
      including the recombinant plasmid group, empty plasmid group and control group.
      Using gene transfection technique to transfer Period2 gene into tumor tissues,
      tested the expression of Period2 mRNA in tumor tissues by real-time quantitative
      PCR after transfection into all nude mice, monitored the transplant tumor growth
      and calculating the tumor inhibition rate, detected the antiapoptotic gene BRE,
      apoptosis related tumor necrosis factor receptor (TNFR1) and tumor suppressor
      gene NIX in tumor tissues by real-time PCR and western blot in different groups.
      RESULTS: (1) The expression level of Period2 mRNA in tumor tissues among ovarian
      cancer group stage I, II and III were respectively 2.59 +/- 0.50, 0.47 +/- 0.08
      and 0.42 +/- 0.08, but benign tumor group was 6.59 +/- 1.05. The expression level
      of Period2 protein in ovarian cancer group stage I, II and III were respectively
      0.835 +/- 0.087, 0.412 +/- 0.035 and 0.199 +/- 0.031, while benign tumor group
      was 0.874 +/- 0.094. The expression level of Period2 mRNA and protein in benign
      tumor group was higher than those in ovarian cancer group stage I, II or III (P <
      0.01). With ovarian cancer stage increased, the expression of Period2 mRNA and
      protein were decreased or absent (P < 0.05). (2) Two weeks after transfection,
      the expression level of Period2 mRNA in recombinant plasmid group tumor tissue
      was significantly higher than those in the empty plasmid group or the control
      group (6.11 +/- 0.56 vs 0.50 +/- 0.09 vs 0.44 +/- 0.08, respectively; P < 0.01),
      the transplanted tumor volume of recombinant plasmid group was significantly less
      than those in empty plasmid group or the control group [(486 +/- 70) mm(3) vs
      (835 +/- 106) mm(3) vs (846 +/- 110) mm(3), respectively; P < 0.01], the tumor
      inhibition rate of the recombination plasmid group was as high as 42.9%, that was
      significantly higher than those in the empty plasmid group and the control group
      (3.8% and 0, respectively; P < 0.05). (3) The expression level of BRE mRNA and
      protein in transplanted tumor tissues in the recombinant plasmid group were
      significantly lower than those in empty plasmid group and the control group; the
      expression level of TNFR1 and NIX were significantly higher than those in the
      empty plasmid group and the control group (all P < 0.05). CONCLUSIONS: Period2
      mRNA and protein expression are absent in ovarian cancer of advanced stage.
      Transfection and stable expression of Period2 gene could slow down the growth of
      ovarian cancer, and the tumor inhibition rate could be significantly increased.
      Period2 gene may promote ovarian cancer cells apoptosis through inhibition of BRE
      gene expression and promoting TNFR1, NIX gene expression to exert anti-tumor
      effect.

PMID- 26311554
TI  - [Identification and characterization of stem cells in an ovarian cancer cell line
      and examination their drug resistance].
AB  - OBJECTIVE: To isolate side population (SP) cells from an established ovarian
      cancer (OC) cell line, characterize these cells, and examine their drug
      resistance. METHODS: SP and non-SP (NSP) cells were isolated by fluorescence
      activated cell sorting (FACS), and cultured in differential conditions, then
      detected their SP ratio to compare their capability of differentiation and self
      renewal. Moreover, SP and NSP cell tumorigenesis was examined by subcutaneous and
      intraperitoneal injection of these cells to nonobes ediabetic (NOD)-severe
      combined immundeficient (SCID) mice. Drug resistance to cisplatin was examined by
      cell counting kit-8 (CCK-8). RESULTS: SP cells could be isolated stablly and
      insistently. There was (4.81 +/- 0.43)% of SP cells in the established OC cell
      line and (4.89 +/- 0.33)% of SP cells after cultured the isolated SP cells in
      differentiation condition, and there was no significant different between these
      two quantities (P > 0.05). However, after cultured the NSP cells, there was only
      (0.10 +/- 0.03)% of SP cells which was significantly lower than that contained in
      the OC cell line (P < 0.01). In the tumorigenesis assay 1.0 * 10(3) SP cells were
      injected subcutaneously and formed the xenografted tumors in 6 weeks (3/3), and
      1.0 * 10(4) NSP cells were injected subcutaneously and did not form xenografted
      tumors in 12 weeks (0). The tumorigenic capability of SP cells was higher than
      that of NSP cells (P < 0.01). Both the original and the xenografted tumors were
      low differentiated serous cystadenocarcinomas and expressed the ovarian serous
      cystadenocarcinomas CA125 marker after stained by HE and immunohistochemistry.
      Simultaneously, the SP cells were also capable to form tumors as shown by
      intraperitoneal injection. In the drug resistance assay shown that the 50%
      inhibitory concentration (IC50) of the SP and NSP cells were respectively (2.33
      +/- 0.14) ug/ml and (1.60 +/- 0.04) ug/ml (P < 0.05). After treated the unsorted
      OC cells with cisplatin, the quantity of SP cells increased to (40.10 +/- 4.22)%
      and there was significant difference, when compared to the untreated cells which
      was (4.81 +/- 0.43)% (P < 0.01). The SP cells survival rate was (58.7 +/- 3.3)%
      when treated with cisplatin at its IC50 dose, and the rate decreased to (7.2 +/-
      1.3)% (P < 0.01) when verapamil was present. CONCLUSIONS: The SP cells could be
      isolated from the established OC cell line. They had the capacities of self
      renewal, differentiation, and tumorigenesis, and the new tumor demonstrated the
      original tumor's phenotype. The SP cells also had stem cells' biological
      characteristics and is resistant to cisplatin.

PMID- 26311556
TI  - Decline in US heart disease slows in younger adults, study finds.

PMID- 26311555
TI  - Thermodynamic Proxies to Compensate for Biases in Drug Discovery Methods.
AB  - PURPOSE: We propose a framework with simple proxies to dissect the relative
      energy contributions responsible for standard drug discovery binding activity.
      METHODS: We explore a rule of thumb using hydrogen-bond donors, hydrogen-bond
      acceptors and rotatable bonds as relative proxies for the thermodynamic terms. We
      apply this methodology to several datasets (e.g., multiple small molecules
      profiled against kinases, Mycobacterium tuberculosis (Mtb) high throughput
      screening (HTS) and structure based drug design (SBDD) derived compounds, and FDA
      approved drugs). RESULTS: We found that Mtb active compounds developed through
      SBDD methods had statistically significantly larger PEnthalpy values than HTS
      derived compounds, suggesting these compounds had relatively more hydrogen bond
      donor and hydrogen bond acceptors compared to rotatable bonds. In recent FDA
      approved medicines we found that compounds identified via target-based approaches
      had a more balanced enthalpic relationship between these descriptors compared to
      compounds identified via phenotypic screens CONCLUSIONS: As it is common to
      experimentally optimize directly for total binding energy, these computational
      methods provide alternative calculations and approaches useful for compound
      optimization alongside other common metrics in available software and databases.

PMID- 26311557
TI  - The effect of maternal obesity on the expression and functionality of placental P
      glycoprotein: Implications in the individualized transplacental digoxin treatment
      for fetal heart failure.
AB  - INTRODUCTIONS: Placental P-glycoprotein (P-gp) plays a significant role in
      controlling digoxin transplacental rate. Investigations on P-gp regulation in
      placenta of women with different pregnant pathology are of great significance to
      the individualized transplacental digoxin treatment for fetal heart failure
      (FHF). This study aimed to explore the effect of maternal obesity on the
      expression and functionality of placental P-gp both in human and in mice.
      METHODS: Placenta tissues from obese and lean women were collected. Female C57BL
      mice were fed with either a normal chow diet or a high-fat diet for 12 weeks
      before mating and throughout pregnancy. Maternal plasma glucose, HDL-C, LDL-C,
      TC, TGs, insulin, IL-1beta, IL-6 and TNF-alpha concentrations was detected.
      Placental ABCB1/Abcb1a/Abcb1b/IL-1beta/IL-6/TNF-alpha mRNA and P-gp/IL-1beta/IL
      6/TNF-alpha protein expression were determined by real-time quantitative PCR and
      western-blot, respectively. Maternal plasma and fetal-unit digoxin concentrations
      were detected by a commercial kit assay. RESULTS: Both ABCB1 gene mRNA and
      protein expression of obesity group was significantly lower than that of control
      group in human. The high-fat dietary intervention resulted in an overweight
      phenotype, a significant increased Lee's index, higher levels of plasma glucose,
      HDL-C, LDL-C, insulin and TGs, increased peri-renal and peri-reproductive gland
      adipose tissue weight, and larger size of adipose cell. Compared with control
      group at the same gestational day (E12.5, E15.5, E17.5), placental Abcb1a mRNA
      and P-gp expression of obese group were significantly decreased in mice, while
      digoxin transplacental rates were significantly increased. Higher maternal plasma
      IL-1beta/TNF-alpha concentrations and placental IL-1beta/TNF-alpha expression
      were observed in obesity groups in comparison with control group at the same
      gestational age. CONCLUSIONS: Maternal obesity could inhibit placental P-gp
      expression and its functionality both in human and in mice, which might be
      resulted from a heightened inflammatory response.

PMID- 26311558
TI  - Evaluation of a multi-fiber exchange solid-phase microextraction system and its
      application to on-site sampling.
AB  - Until recently, multiple solid-phase microextraction fibers could not be
      automatically desorbed in a single gas chromatographic sequence without manual
      intervention from an operator. This drawback had been a critical issue,
      particularly during the analysis of numerous on-site samples taken with various
      fiber assemblies. Recently, a Multi-Fiber Exchange system, designed to overcome
      this flaw found in other commercially available autosamplers, was released. In
      the current research, a critical evaluation of the Multi-Fiber Exchange system
      performance in terms of storage stability and long-term operation is presented.
      It was established in the course of our research that the Multi-Fiber Exchange
      system can operate continuously and precisely for multiple extraction/injection
      cycles. However, when the effect of residence time of commercial fibers on the
      Multi-Fiber Exchange tray was evaluated, results showed that among the evaluated
      fiber coatings, Carboxen/polydimethylsiloxane was the only coating capable of
      efficient storage on the tray for up to 24 h after field sampling without
      suffering significant loss of analytes (<=10% for benzene, toluene, ethylbenzene,
      o-xylene, decane, and limonene). Additionally, the system capability for high
      throughput analysis was demonstrated by the unattended desorption of multiple
      fibers after on-site sampling of toluene, indoor air levels, in a polymer
      synthesis lab. 

PMID- 26311559
TI  - Objective Assessment of Facial Rejuvenation After Massive Weight Loss.
AB  - BACKGROUND: While the literature is replete with articles about body contouring
      after bariatric surgery, little information exists regarding the outcomes of
      facelift following massive weight loss (MWL). A case report and a technique
      article are the only sources available addressing this issue. This pilot study
      objectively examines the effects of MWL in the cervicofacial region and results
      after facelift. METHODS: A retrospective review of seven patients who underwent
      facelift after MWL (>100 pounds) was performed. Patient's change in appearance
      was objectively evaluated using an apparent age model. Forty blinded reviewers
      assessed pre- and postoperative photographs of seven MWL and eleven non-MWL
      female patients. The reviewers estimated the apparent age for each subject.
      Reduction in apparent age was calculated by comparing patient's apparent age
      against actual age. RESULTS: The preoperative apparent age of MWL patients was
      5.1 years older than their actual age (p < 0.02) compared to the increased
      preoperative apparent age of 1.2 years in non-MWL subjects (p > 0.05); suggesting
      MWL patients appear older than their actual age. Post-operatively, the apparent
      age reduction in MWL patients was 6.0 years; and their apparent age after surgery
      was 0.9 year less than their actual age (p > 0.05). In contrast, the control
      group exhibited an apparent age reduction of 5.4 years and a postoperative
      apparent age 4.2 years younger than their actual age (p < 0.01). Apparent age
      reduction was not significantly different for the two groups (p > 0.05). Age,
      BMI, and follow-up were similar between groups (p > 0.05). CONCLUSIONS: MWL may
      accelerate apparent cervicofacial aging. Facelift following MWL enhances
      cervicofacial appearance and significantly reduces apparent age. We hope this
      study stimulates further interest in the study of facial esthetics in this
      increasing population. 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- 26311560
TI  - The Modification of Five-Flap Z-Plasty for Web Contracture.
AB  - BACKGROUND: Web contractures are fairly commonly encountered in those who have
      suffered from burn injury or other trauma. Numerous local flaps have been adopted
      previously. The five-flap Z-plasty is one that has been used frequently. To
      release the scar as much as possible, based on the traditional design, we
      developed a modified technique of the five-flap Z-plasty to reconstruct the
      axillary and elbow web contractures. Hence, the length of the axis of the
      cicatrix could be much lengthened. METHODS: Twenty patients (12 females and 8
      males, 7 to 48 years-old) with 27 web contractures were arranged for the
      operation using the new flap. The contractures were formed on by burn injury in
      17 patients, surgery in 2 patients, and traumatic cicatrix in 1 case. All
      patients were operated on using a modified five-flap Z-plasty to reach the aim of
      maximum contracture relaxation. RESULTS: All flaps survived well. No flap tip
      necrosis occurred. Good function was gained in all patients postoperatively by
      the one year average follow-up. There was no recurrence. The contracture band was
      freed satisfactorily. CONCLUSION: The technique is very easy to execute and can
      be used both in web and linear contractures. With the virtue of extending the
      length of the scar axis to a higher degree compared to the traditional method, we
      suggest this modified five-flap Z-plasty application. LEVEL OF EVIDENCE IV: This
      journal requires that authors assign a level of evidence to each article. For a
      full description of these Evidence-Based Medicine ratings, please refer to the
      Table of Contents or the online Instructions to Authors www.springer.com/00266.

PMID- 26311561
TI  - Is the SMAS Flap Facelift Safe? A Comparison of Complications Between the Sub
      SMAS Approach Versus the Subcutaneous Approach With or Without SMAS Plication in
      Aesthetic Rhytidectomy at an Academic Institution.
AB  - BACKGROUND: For treating the aging face, a facelift is the surgical standard. A
      variety of techniques have been described. The purpose of the current study is to
      evaluate the safety of the sub-SMAS facelift compared to the subcutaneous
      facelift with or without SMAS plication. METHODS: A retrospective chart review
      was conducted on all patients who underwent facelift surgery between 2003 and
      2011. Patients included in the study were seeking elective improvement of facial
      appearance. All charts were reviewed to identify the presence of hematoma,
      seroma, deep venous thrombosis, skin loss, unfavorable scar, wound infection, or
      motor and sensory deficit following the operation. The primary outcome was
      overall complication rate. RESULTS: A total of 229 facelifts were included; 143
      patients underwent a subcutaneous facelift with or without SMAS plication and 86
      underwent a sub-SMAS facelift. For the subcutaneous facelifts, 88% of the
      patients were female with a mean age of 62 years. For the sub-SMAS dissections,
      88% of the patients were female with a mean age of 59 years. The overall
      complication rate was 29.4% (n = 42) for patients who underwent a subcutaneous
      facelift compared to 24.4% (n = 21) for patients with a sub-SMAS facelift (p =
      0.4123). Analysis of each individual complication failed to yield any
      statistically significant difference between the two groups. CONCLUSIONS: In the
      present study, sub-SMAS facelift complication rates were not statistically
      different compared to those of subcutaneous facelift with or without SMAS
      plication. These data suggest that sub-SMAS dissection can be performed with
      similar safety compared to the traditional subcutaneous facelift, with the
      potential additional advantage of the SMAS flap elevation. LEVEL OF EVIDENCE IV:
      This journal requires that authors assign a level of evidence to each article.
      For a full description of these Evidence-Based Medicine ratings, please refer to
      the Table of Contents or the online Instructions to Authors
      www.springer.com/00266.

PMID- 26311562
TI  - Prevalence, Long-term Development, and Predictors of Psychosocial Consequences of
      False-Positive Mammography among Women Attending Population-Based Screening.
AB  - BACKGROUND: Cancer screening aims to detect cancer at an asymptomatic stage,
      although side effects from screening also occur. We investigated the prevalence,
      longitudinal development, and predictors of psychosocial consequences of false
      positive breast cancer screening. METHODS: Three hundred ninety-nine women with
      false-positive screening mammography responded to the Consequences of Screening
      Breast Cancer (COS-BC) questionnaire immediately after a negative diagnosis (free
      from breast cancer) following recall examination(s) (baseline), and 6 and 12
      months later. Age-matched controls (n = 499) with a negative mammogram responded
      to the COS-BC at the same occasions. Five COS-BC scales (Sense of dejection,
      Anxiety, Behavioral, Sleep, and Existential values) were used as outcome
      measures. RESULTS: Women with false-positive mammography had consistently higher
      prevalence of all five consequences compared with controls (P < 0.001). The
      prevalences decreased between baseline and 6 months (P < 0.001) but were stable
      between 6 and 12 months (P >= 0.136). Early recall profoundly predicted long-term
      consequences for all five outcomes (OR, 3.05-10.31), along with dissatisfaction
      with information at recall (OR, 2.28-2.56), being foreign-born (OR, 2.35-3.71),
      and lack of social support (OR, 1.13-1.25). CONCLUSION: This 1-year longitudinal
      study shows that women experience psychosocial consequences of false-positive
      screening mammography. Early recall should be performed cautiously, and provision
      of information as well as social support may reduce psychosocial consequences.
      IMPACT: Although delivery of population-based screening reduces breast cancer
      mortality, it also raises the issue of its impact on the psychosocial well-being
      of healthy women. Our findings identify predictors that can be targeted in future
      efforts to reduce the side effects of mammographic screening.

PMID- 26311563
TI  - Incidence and risk factors for symptomatic heart failure after catheter ablation
      of atrial fibrillation and atrial flutter.
AB  - AIMS: To determine the incidence and risk factors for development of symptomatic
      heart failure (HF) following catheter ablation for atrial fibrillation (AF) and
      atrial flutter. METHODS AND RESULTS: We prospectively enrolled consecutive
      patients undergoing pulmonary vein isolation (PVI) or cavotricuspid isthmus (CTI)
      ablation between November 2013 and June 2014. Post-discharge symptoms were
      assessed via telephone follow-up and clinic visits. The primary outcome was
      symptomatic HF requiring treatment with new/increased diuretic dosing. Secondary
      outcomes were prolonged index hospitalization and readmission for HF <=30 days.
      Univariate and multivariable logistic regressions were used to assess the
      relationship between patient/procedural characteristic and post-ablation HF.
      Among 111 PVI patients [median age 62.0 years; left ventricular ejection fraction
      (LVEF) 55%], 29 patients (26.1%) developed symptomatic HF, 6 patients (5.4%)
      required prolonged index hospitalization, and 8 patients (7.2%) were readmitted
      for HF. In univariate analyses, persistent AF [odds ratio (OR) 2.97, P = 0.02],
      AF at start of the procedure (OR 2.99, P = 0.01), additional ablation lines (OR
      11.07, P < 0.0001), and final left atrial pressure (OR 1.10 per 1 mmHg increase,
      P = 0.02) were associated with HF development. Peri-procedural diuresis, net
      fluid balance, and LVEF were not correlated. In multivariable analyses, only
      additional ablation lines (ORadj 9.17, P = 0.007) were independently associated
      with post-ablation HF. Six patients (16.7%) developed HF after CTI ablation.
      CONCLUSION: A 26.1% of patients undergoing PVI and 16.7% of patients undergoing
      CTI ablation developed symptomatic HF when prospectively and uniformly assessed.
      12.6% of patients experienced prolonged index hospitalizations or readmission for
      management of HF within 1 week after PVI. Improved understanding of risk factors
      for post-ablation HF may be critical in developing strategies to address during
      AF ablation.

PMID- 26311564
TI  - Role of inflammation in benign prostatic hyperplasia development among Han
      Chinese: A population-based and single-institutional analysis.
AB  - OBJECTIVES: To explore whether asymptomatic inflammatory prostatitis is
      associated with prostatic enlargement beyond that of benign prostatic hyperplasia
      patients without asymptomatic inflammatory prostatitis, and whether asymptomatic
      inflammatory prostatitis affects long-term outcomes of transurethral resection of
      the prostate. METHODS: The present study involved 106 benign prostatic
      hyperplasia patients who underwent transurethral resection of the prostate.
      Clinical and pathological parameters were compared between those with benign
      prostatic hyperplasia associated with asymptomatic inflammatory prostatitis and
      those with benign prostatic hyperplasia alone. RESULTS: A total of 55 patients
      (52%) were found to have benign prostatic hyperplasia and asymptomatic
      inflammatory prostatitis, whereas 51 patients (48%) had benign prostatic
      hyperplasia alone. The prostate volume of the benign prostatic
      hyperplasia/asymptomatic inflammatory prostatitis group was significantly larger
      than the benign prostatic hyperplasia alone group: 68.1 cm3 (interquartile range
      45.7-86.3) versus 44.1 cm3 (interquartile range 30.9-72.1), P = 0.036. In terms
      of histopathological analysis, benign prostatic hyperplasia/asymptomatic
      inflammatory prostatitis patients were more likely to show mild (53%), focal
      (67%) and stromal (40%) prostatic inflammation in our study. Furthermore,
      statistically significant differences of International Prostate Symptom Score
      were found 3 years after transurethral resection of the prostate, with benign
      prostatic hyperplasia/asymptomatic inflammatory prostatitis patients reporting
      higher (worse) scores than benign prostatic hyperplasia alone patients (P =
      0.025). CONCLUSIONS: Chronic prostatic inflammatory process might progressively
      conduce to benign prostatic hyperplasia development, which can also result in
      prostate enlargement and worsen long-term postoperative International Prostate
      Symptom Scores. Multicenter studies with larger cohorts and longer follow-up
      periods are required to confirm these findings.

PMID- 26311565
TI  - Cytoreductive surgery and perioperative intraperitoneal chemotherapy for
      peritoneal carcinomatosis in the elderly.
AB  - BACKGROUND: Peritoneal carcinomatosis is life-threatening without cytoreductive
      surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC). Only a few
      studies in the literature addressed the relationship between age and outcomes of
      peritonectomy. This study was designed to review the clinical outcomes in elderly
      patients who underwent CRS and PIC. METHODS: This is a retrospective study of
      prospectively collected data of 611 consecutive patients with peritoneal
      carcinomatosis who underwent CRS and PIC by the same surgical team at St George
      Hospital in Sydney, Australia, between January 1996 and December 2013. Patients
      were divided into two groups; group 1 (<65 years old, n = 487) and group 2 (>= 65
      years old, n = 124). Subgroup analysis was performed in patients who were >=75
      years old (n = 20). A significant difference was defined as p < 0.05. RESULTS:
      There was no significant statistical difference in terms of mean total hospital
      stay, intensive care unit stay, high dependency unit stay and complication rates.
      Postoperative mortality was 2 and 3 % in groups 1 and 2, respectively. Overall
      survival did not reach a statistical significance between the two groups. In
      subgroup analysis, patients showed similar morbidity results to patients who were
      <65 years old. CONCLUSIONS: CRS and PIC can be safely done in the elderly. Age
      alone should not be the single exclusion criterion but rather taken into
      consideration along with other factors to determine the suitability of elderly
      patients.

PMID- 26311566
TI  - Medicine preparation errors in ten Spanish neonatal intensive care units.
AB  - This study assessed the rate of errors in intravenous medicine preparation at the
      bedside in neonatal intensive care units vs the preparation error rate in a
      hospital pharmacy service. We conducted a prospective observational study between
      June and September 2013. Ten Spanish neonatal intensive care units and one
      hospital pharmacy service participated in the study. Two types of preparation
      errors were considered: calculation errors and accuracy errors. A total of 522
      samples were collected: 238 of vancomycin, 139 of gentamicin, 39 of phenobarbital
      and 88 of caffeine citrate preparations. Of these, 444 samples were collected by
      nurses in neonatal intensive care units, and 60 were provided by the hospital
      pharmacy service. Overall, 18 samples were excluded from the analysis. We
      detected calculation errors in 6/444 (1.35%) and accuracy errors in 243/444
      (54.7%) samples from the neonatal intensive care units. In contrast, in samples
      from the hospital pharmacy service, no calculation errors were detected, but
      there were accuracy errors in 23/60 (38.3%) samples. CONCLUSION: While
      calculation errors can be eliminated using protocols based on standard drug
      concentrations, accuracy error rates depend on several variables that affect both
      neonatal intensive care units and hospital pharmacy services. WHAT IS KNOWN:
      Medication use is associated with a risk of errors and adverse events. Medication
      errors are more frequent and have more severe consequences in paediatric
      patients. Lack of knowledge of drug pharmacokinetics and pharmacodynamics in
      relation to physiological immaturity makes neonates more vulnerable to medication
      errors. WHAT IS NEW: Calculation errors are avoided using concentration standard
      preparation protocols. Accuracy in the preparation process depends mainly on the
      degree to which commercial drug preparations meet current legal requirements and
      the syringes and preparation techniques used.

PMID- 26311567
TI  - Congenital extrahepatic portosystemic shunt: an underdiagnosed but treatable
      cause of hepatopulmonary syndrome.
AB  - Congenital extrahepatic portosystemic shunt (CEPS) is a rare malformation of the
      mesenteric vasculature, which may lead to severe complications. In this report,
      we describe a case series of three children with type II CEPS (presenting as
      hypoxemia) and hepatopulmonary syndrome (HPS). The first patient was a 4-year-old
      male who did not receive any specific treatment and subsequently died of brain
      abscess 5 years after the diagnosis. The second patient was a 10-year-old female
      with a 5-year history of cyanosis and dyspnea on exertion. She had partial
      regression of hypoxemia and improved exercise tolerance at 8 months after a
      surgical shunt closure. The third patient was a 4-year-old male with a 3-year
      history of cyanosis and decreased exercise tolerance. He had full regression of
      hypoxemia at 3 months after a transcatheter shunt closure. CONCLUSION: These
      results indicate that CEPS may present in children with unexplained hypoxemia,
      which may lead to devastating clinical consequences. Closure of portosystemic
      shunts may result in resolution of HPS in type II CEPS and the length of period
      for resolution varies depending on the severity of HPS. WHAT IS KNOWN: Congenital
      extrahepatic portosystemic shunt (CEPS) is a rare cause of hepatopulmonary
      syndrome (HPS). There have been few reports in the literature about the
      management and outcome of HPS in children with CEPS. WHAT IS NEW: CEPS may
      present in children with unexplained hypoxemia, which may lead to devastating
      clinical consequences. Closure of portosystemic shunts may result in resolution
      of HPS in type II CEPS.

PMID- 26311568
TI  - Distal humerus prosthetic hemiarthroplasty: midterm results.
AB  - Treatment of comminuted distal humeral fractures remains challenging. Open
      reduction-internal fixation remains the preferred treatment, but is not always
      feasible. In selected cases with non-reconstructable or highly comminuted
      fractures, total elbow arthroplasty has been used, however, also with relatively
      high complication and failure rates. Distal humerus prosthetic hemiarthroplasty
      (DHA) may be an alternative in these cases. The purpose of this study was to
      report the midterm results of six patients that were treated by DHA for acute and
      salvage treatment of non-reconstructable fractures of the distal humerus. All six
      patients were treated by DHA for acute and salvage treatment of non
      reconstructable fractures of the distal humerus. Medical records were reviewed,
      and each patient was seen in the office. Mean follow-up was 54 months (range 21
      76 months). Implant survival was 100 %. Three were pain free and three had mild
      or moderate residual pain. Average flexion-extension arc was 95.8 degrees  (range
      70 degrees -115 degrees ) and average pronation-supination arc was 165 degrees 
      (range 150 degrees -180 degrees ). In three, there was some degree of
      instability, which was symptomatic in one. One had motoric and sensory sequelae
      of a partially recovered traumatic ulnar nerve lesion. According to the Mayo
      Elbow Performance Score, there were three excellent, one good and two poor
      results. Four were satisfied with the final result, and two were not. In this
      case series of six patients with DHA for non-reconstructable distal humerus
      fractures, favorable midterm follow-up results were seen; however, complications
      were also observed. 

PMID- 26311569
TI  - Survey of Foundation Year 1 doctors caring for the dying; what do they see, do
      and need to perform this role, following removal of the Liverpool Care Pathway?

PMID- 26311570
TI  - Patients' experiences of a new integrated breathlessness support service for
      patients with refractory breathlessness: Results of a postal survey.
AB  - BACKGROUND: We developed a new single point of access to integrated palliative
      care, respiratory medicine and physiotherapy: the breathlessness support service
      for patients with advanced disease and refractory breathlessness. This study
      aimed to describe patients' experiences of the service and identify the aspects
      valued. DESIGN: We attempted to survey all patients who had attended and
      completed the 6-week breathlessness support service intervention by sending them
      a postal questionnaire to self-complete covering experience, composition,
      effectiveness of the BSS and about participation in research. Data were analysed
      using descriptive statistics and thematic analysis of free text comments.
      RESULTS: Of the 70 postal questionnaires sent out, 25 (36%) returned. A total of
      21 (84% (95% confidence interval: 69%-98%)) responding patients reported that
      they definitely found the breathlessness support service helpful and 13 (52% (95%
      confidence interval: 32%-72%)) rated the breathlessness support service as
      excellent. A total of 21 (84% (95% confidence interval: 69%-98%)) patients
      reported that the breathlessness support service helped with their management of
      their breathlessness along with additional symptoms and activities (e.g. mood and
      mobility). Four key themes were identified: (1) personalised care, (2) caring
      nature of the staff, (3) importance of patient education to empower patients and
      (4) effectiveness of context-specific breathlessness interventions. These were
      specific aspects that patients valued. CONCLUSION: Patients' satisfaction with
      the breathlessness support service was high, and identified as important to this
      was a combination of personalised care, nature of staff, education and
      empowerment, and use of specific interventions. These components would be
      important in any future breathlessness service.

PMID- 26311571
TI  - Longitudinal changes and predictors of prolonged grief for bereaved family
      caregivers over the first 2 years after the terminally ill cancer patient's
      death.
AB  - BACKGROUND: A significant minority of bereaved caregivers experience prolonged
      grief. However, few longitudinal studies have examined prolonged grief,
      especially in an Asian context. AIM: We explored longitudinal changes and factors
      predicting prolonged grief in bereaved caregivers of terminally ill Taiwanese
      cancer patients. DESIGN: Observational, prospective, and longitudinal. Prolonged
      grief symptoms were measured with the PG-13 at 6, 13, 18, and 24 months postloss.
      SETTING/PARTICIPANTS: A convenience sample of 493 caregivers (83.3% participation
      rate) of terminally ill cancer patients was recruited from a medical center in
      Taiwan. RESULTS: The prevalence of prolonged grief decreased significantly over
      time from the patient's death (7.73%, 1.80%, 2.49%, and 1.85% at 6, 13, 18, and
      24 months postloss, respectively, p < 0.05 at all times in reference to 6 months
      postloss). Caregivers' likelihood of prolonged grief was significantly higher if
      they had severe preloss depressive symptoms, negatively perceived their
      relative's dying situation, and were poorly prepared for the patient's death.
      However, the likelihood of prolonged grief decreased significantly with greater
      perceived concurrent social support and subjective caregiving burden right before
      the patient's death. CONCLUSION: Prolonged grief in bereavement diminished over
      time and was predicted by modifiable factors before, during, and after
      bereavement. To facilitate bereavement adjustment and avoid prolonged grief,
      healthcare professionals should develop and provide at-risk caregivers with
      effective interventions starting when patients are still alive to improve their
      dying experience, to facilitate preparedness for the patient's forthcoming death,
      to alleviate caregivers' preloss depressive symptoms, and to enhance their
      perceived postloss social support.

PMID- 26311572
TI  - Scientific Evaluation of Pharmacological Treatment of Osteoarthritis in the Canon
      of Medicine.
AB  - Osteoarthritis is the most common articular disease worldwide. Nonetheless,
      common osteoarthritis treatments are either not effective or associated with side
      effects. Now the materials derived from plants have found a relevant place in
      drug discovery. Until the mid-18th century, osteoarthritis in all medical schools
      worldwide had been managed as general arthritis. Avicenna, the famous scholar of
      Iranian traditional medicine has provided a long list of herbs that have been
      used traditionally to treat arthritis. To gain this worthy list, we searched his
      most famous medical masterpiece: Canon of Medicine Some of these materials are
      investigated and employed by modern medicine. However, it is difficult to ignore
      that still more of these naturally occurring materials could be of use in modern
      medicine not only to prevent osteoarthritis progression but also osteoarthritis
      management as natural anti-inflammatory drugs. 

PMID- 26311573
TI  - Effectiveness of a Pilot Mindfulness Program in Volunteers of a Breast Cancer
      Association.
AB  - It has been usually observed that medical and health personnel, volunteers, and
      social workers who work with cancer and chronic patients may have higher rates of
      compassion fatigue and symptoms of anxiety and depression. The purpose of this
      study was to examine the benefits of a pilot mindfulness program in a sample of 7
      volunteers of a foundation that supports women with breast cancer. The variables
      analyzed were depression, anxiety, compassion fatigue, work stress, and negative
      and positive affect. The results showed that the mindfulness program had a
      positive impact, reducing the symptoms of anxiety and depression and increasing
      emotional well-being. Participants also reported that the program helped them be
      more relaxed, identify their emotions, enjoy their time and environment better,
      increasing the value of life, and facilitate communication among the volunteers.
      The program produced positive changes in participants, powering personal areas
      and increasing emotional well-being. 

PMID- 26311575
TI  - Effect of Micronized Purified Flavonoid Fraction Therapy on Endothelin-1 and TNF
      alpha Levels in Relation to Antioxidant Enzyme Balance in the Peripheral Blood of
      Women with Varicose Veins.
AB  - OBJECTIVE: The aetiology of varicose veins involves various factors and
      pathomechanisms including endothelial cell activation or dysfunction, venous
      hypertension, vein wall hypoxia, shear stress disturbances, inflammatory reaction
      activation or free radical production. To improve our understanding of the
      mechanisms of potential pharmacological interventions for chronic venous disease,
      we evaluated the influence of micronized purified flavonoid fraction (MPFF) on
      the relationship between antioxidant enzyme balance, endothelin-1 (ET-1) and
      tumour necrosis factor-alpha (TNF-alpha) levels. MATERIAL AND METHODS: Blood
      samples were obtained from 89 women with primary varicose veins; 34 were treated
      with MPFF and 55 did not receive any phlebotropic drug treatment. For the
      evaluation of the blood antioxidant enzyme balance, catalase (CAT) and superoxide
      dismutase (SOD) activity was assessed and the CAT/SOD ratio was calculated.
      RESULTS: Patients taking MPFF had significantly lower ET-1 levels than those not
      taking MPFF [median (25-75th quartile): 24.2 (22.30-27.87) vs 37.62 (24.9-44.58)
      pg.ml-1; p <0.05]. In those taking MPFF, a higher CAT/SOD ratio [39.8 (24.7-72.6)
      vs 28.8 (16.3-57.7); p<0.05] and a lower TNF-alpha concentration [6.82 (4.42
      13.39) vs 12.94 (6.01-27.33) pg.ml<sup>-1</sup>; p<0.05] was also observed. In
      women not taking MPFF, ET-1 levels increased with the CAT/SOD ratio. In those
      taking MPFF, the ET-1 level was stable at approximately 25.0 pg.ml<sup>-1</sup>!
      up to a CAT/SOD ratio of 100. TNF-alpha level increased continuously with an
      increasing CAT/SOD ratio; however, the highest levels of TNF-alpha were observed
      in women not taking MPFF. CONCLUSION: We demonstrate the ability of MPFF to
      effectively lower the levels of ET-1 and TNF-alpha in patients with chronic
      venous disease. Further investigations are needed to define the therapeutic
      potential of MPFF including the potential effect on chronic subclinical
      inflammation, antioxidant imbalance and vascular dysfunction during the
      development of chronic venous disease.

PMID- 26311574
TI  - Identification and Treatment of Patients with Homozygous Familial
      Hypercholesterolaemia: Information and Recommendations from a Middle East
      Advisory Panel.
AB  - We present clinical practice guidelines for the diagnosis and treatment of
      homozygous familial hypercholesterolaemia (HoFH) in the Middle East region. While
      guidelines are broadly applicable in Europe, in the Middle East we experience a
      range of confounding factors that complicate disease management to a point
      whereby the European guidance cannot be applied without significant modification.
      Specifically, for disease prevalence, the Middle East region has an established
      epidemic of diabetes and metabolic syndrome that can complicate treatment and
      mask a clinical diagnosis of HoFH. We have also a high incidence of
      consanguineous marriages, which increase the risk of transmission of recessive
      and homozygous genetic disorders. This risk is further augmented in autosomal
      dominant disorders such as familial hypercholesterolaemia (FH), in which a range
      of defective genes can be transmitted, all of which contribute to the phenotypic
      expression of the disease. In terms of treatment, we do not have access to
      lipoprotein apheresis on the same scale as in Europe, and there remains a
      significant reliance on statins, ezetimibe and the older plasma exchange methods.
      Additionally, we do not have widespread access to anti-apolipoprotein B therapies
      and microsomal transfer protein inhibitors. In order to adapt existing global
      guidance documents on HoFH to the Middle East region, we convened a panel of
      experts from Oman, Saudi Arabia, UAE, Iran and Bahrain to draft a regional
      guidance document for HoFH. We also included selected experts from outside the
      region. This panel statement will form the foundation of a detailed appraisal of
      the current FH management in the Middle Eastern population and thereby provide a
      suitable set of guidelines tailored for the region. 

PMID- 26311576
TI  - Assessment of dose-effect and therapeutic time window in preclinical studies of
      rhEGF and GHRP-6 coadministration for stroke therapy.
AB  - BACKGROUND: Stroke continues to be a leading cause of mortality and morbidity
      worldwide, and novel therapeutic options for ischaemic stroke are urgently
      needed. In this context, drug combination therapies seem to be a viable approach,
      which has not been fully explored in preclinical studies. OBJECTIVES: In this
      work, we assessed the dose-response relationship and therapeutic time window, in
      global brain ischaemia, of a combined therapeutic approach of recombinant human
      epidermal growth factor (EGF) and growth hormone-releasing peptide-6 (GHRP-6).
      METHODS: Mongolian gerbils underwent 15 minutes occlusion of both common carotid
      arteries. Four different doses of rhEGF, GHRP-6 and these combined agents were
      intraperitoneally administered immediately after the onset of reperfusion. Having
      identified a better response with both agents, rhEGF+GHRP-6 were administered at
      2, 4, 6, 8 or 24 hours after the onset of reperfusion to assess the time window
      of effectiveness. Animals were evaluated daily for neurological deficits. Three
      days post-occlusion, the animals were sacrificed and 2,3,5-triphenyltetrazolium
      chloride was used to quantify infarcted tissues. RESULTS: The coadministration of
      rhEGF and GHRP-6 at doses of 100 and 600 MUg/kg, respectively, administered up to
      4 hours following the ischaemic insult, significantly improved survival and
      neurological outcome, and reduced infarct volume compared with vehicle treatment.
      These results are considered as an additional proof of concept as supporting a
      combined therapeutic approach and justify the further development of this
      preclinical research.

PMID- 26311577
TI  - Fine particulate matter components and mortality in Greater Houston: Did the risk
      reduce from 2000 to 2011?
AB  - Fine particulate matter (less than 2.5MUm in aerodynamic diameter; PM2.5)
      pollution poses a major environmental threat in Greater Houston due to rapid
      economic growth and the numerous PM2.5 sources including ports, vehicles, and the
      largest petrochemical industry in the United States (U.S.). Our objectives were
      to estimate the short-term associations between the PM2.5 components and
      mortality during 2000-2011, and evaluate whether these associations have changed
      over time. A total of 333,317 deaths were included in our assessment, with an
      average of 76 deaths per day. We selected 17 PM2.5 components from the U.S.
      Environmental Protection Agency's Chemical Speciation Network, and then applied
      Poisson regression models to assess the associations between the PM2.5 components
      and mortality. Additionally, we repeated our analysis for two consecutive
      periods: 2000-2005 and 2006-2011. Interquartile range increases in ammonium
      (0.881MUg/m(3)), nitrate (0.487MUg/m(3)), sulfate (2.245MUg/m(3)), and vanadium
      (0.004MUg/m(3)) were associated with an increased risk in mortality of 0.69% (95%
      confidence interval (CI): 0.26, 1.12%), 0.38% (95% CI: 0.11, 0.66%), 0.61% (95%
      CI: 0.15, 1.06%), and 0.58% (95% CI: 0.12, 1.04%), respectively. Seasonal
      analysis suggested that the associations were strongest during the winter months.
      The association between PM2.5 mass and mortality decreased during 2000-2011,
      however, the PM2.5 components showed no notable changes in mortality risk over
      time. Our study indicates that the short-term associations between PM2.5 and
      mortality differ across the PM2.5 components and suggests that future air
      pollution control measures should not only focus on mass but also pollutant
      sources. 

PMID- 26311578
TI  - Quantification of human infection risk caused by rotavirus in surface waters from
      Cordoba, Argentina.
AB  - Fecal contamination of water is a worrying problem because it is associated with
      the transmission of enteric pathogenic microorganisms that can cause many
      infectious diseases. In this study, an environmental survey was conducted to
      assess the level of viral contamination by viable enterovirus and rotavirus
      genome in two recreational rivers (Suquia and Xanaes) of Cordoba, Argentina.
      Quantitative microbial risk assessment (QMRA) was calculated to estimate the risk
      of rotavirus infection. Water sampling was carried out during a one-year period,
      the presence of total and fecal coliforms was determined and water samples were
      then concentrated for viral determination. Cell culture and indirect
      immunofluorescence were applied for enterovirus detection and RT-qPCR for
      rotavirus quantification. Coliform bacteria levels found in Suquia River often
      far exceeded the guideline limits for recreational waters. The Xanaes exhibited a
      lower level of bacterial contamination, frequently within the guideline limits.
      Enterovirus and rotavirus were frequently detected in the monitoring rivers
      (percentage of positive samples in Suquia: 78.6% enterovirus, 100% rotavirus; in
      Xanaes: 87.5% enterovirus, 18.7% rotavirus). Rotavirus was detected at a media
      concentration of 5.7*10(5) genome copies/L (gc/L) in the Suquia and 8.5*10(0)gc/L
      in the Xanaes. QMRA revealed high risk of rotavirus infection in the Suquia, at
      sampling points with acceptable and non-acceptable bacteria numbers. The Xanaes
      showed significantly lower health risk of rotavirus infection but it proved to be
      a public health hazard. The viral occurrence was not readily explained by the
      levels of bacteria indicators, thus viral monitoring should be included to
      determine microbiological water quality. These findings provide the first data of
      QMRA for recreational waters in Argentina and reveal the need for public
      awareness of the health implications of the use of the river waters. 

PMID- 26311579
TI  - Epidemiological study for the assessment of health risks associated with
      graywater reuse for irrigation in arid regions.
AB  - Graywater reuse is rapidly gaining popularity as a viable source of reclaimed
      water, mainly for garden irrigation and toilet flushing. The purpose of this
      study was to determine, by epidemiological survey, the risk for gastroenteritis
      symptoms associated with graywater reuse. The study comprised a weekly health
      questionnaire answered by both graywater users and non-graywater users (control
      group) regarding their health status over a period of 1year, and periodic
      sampling for graywater quality. Participants were also asked to respond to a one
      time lifestyle questionnaire to assess their level of exposure to graywater or
      potable water used in garden irrigation. Graywater quality was typical and
      comparable to previous studies, with average fecal coliform concentration of
      10(3)CFU 100ml(-1). A Cox Proportional Hazards model indicated a somewhat higher
      health risk for the control group (P<0.05), suggesting that there was practically
      no difference in the prevalence of water-related diseases between users of
      graywater and potable water. Since the concentration of pathogens in the current
      study was higher than that suggested by quantitative microbial risk assessment
      (QMRA), yet there was no difference in the prevalence of water-related diseases
      between control and graywater users, it was postulated that QMRA is conservative
      and can safely be used toward the establishment of regulations governing
      graywater reuse. 

PMID- 26311580
TI  - Effects of an antihistamine on carbon and nutrient recycling in streams.
AB  - In stream ecosystems, microbes and macroinvertebrates consume leaf litter
      deposited from the riparian vegetation, and thereby recycle resources tied up in
      the litter. Several environmental variables influence rates of this recycling,
      but it is not well known if common pharmaceuticals, such as antihistamines,
      originating from wastewater effluent, have additional impacts. Exposure to dilute
      concentrations of antihistamines may adversely influence aquatic detritivorous
      invertebrates, because invertebrates use histamines for neurotransmission,
      resulting in hampered recycling of resource tied up in leaf detritus. In this
      study, we therefore investigated if the antihistamine fexofenadine, at a
      concentration of 2000ngl(-1), alters rates of leaf litter decomposition in stream
      microcosms. Stonefly larvae (n=10, per microcosm), together with natural
      microbial communities, served as main decomposer organisms on alder leaf litter.
      First, we used 30 microcosms containing fexofenadine, while the other 30 served
      as non-contaminated controls, and of each 30 microcosms, 14 contained stonefly
      larvae and microbes, while the remaining 16 contained only microbes. We found, in
      contrast to our hypothesis, that fexofenadine had no effect on leaf litter
      decomposition via impacts on the stonefly larvae. However, independent on if
      stoneflies were present or not, concentrations of organic carbon (TOC) and
      nitrogen (N) were strongly affected, with 20-26 and 24-31% lower concentrations
      of TOC and N, respectively, in the presence of fexofenadine. Second, in a scaled
      down follow-up experiment, we found that microbial activity increased by 85%,
      resulting in a 10% decrease in pH, in the presence of fexofenadine. While the
      antihistamine concentration we used is higher than those thus far found in the
      field (1-10ngl(-1)), it is still 100 times lower than the predicted no-effect
      concentration for fexofenadine. As such, our results indicate that low MUg l(-1)
      levels of antihistamines can have an effect on carbon and nutrient recycling in
      aquatic system. 

PMID- 26311582
TI  - Solubilization of herbicides by single and mixed commercial surfactants.
AB  - The solubilization capabilities of micellar solutions of three single
      surfactants, two alcohol alkoxylates B048 and B266, and the tallow alkyl
      ethoxylated amine ET15, and their equimolar mixed solutions toward the herbicides
      flurtamone (FL), metribuzin (MTZ) and mesotrione (MST) were investigated. The
      solubilization capacity was quantified in terms of the molar solubilization ratio
      (MSR), critical micellar concentration (CMC), micelle-water partition coefficient
      (Kmc), binding constant (K1), number of aggregation (Nagg) and Stern-Volmer
      constant (Ksv). The herbicides were greatly solubilized into different loci of
      the micelles: FL within the inner hydrophobic core, MST at the micelle/water
      interface and MTZ in the palisade region. Equimolar binary surfactant mixtures
      did not improve the solubilization of herbicides over those of single components,
      with the exception of MTZ by the B266/ET15 system which enhanced solubilization
      by 10-20%. This enhanced solubilization of MTZ was due to an increased number of
      micelles that arise from both the intermediate Nagg relative to that of the
      single surfactants and the lower CMC. The use of Ksv values was a better
      predictor of the solubilization of polar molecules within binary mixtures of
      these surfactants than the interaction parameter beta(M) from regular solution
      theory (RST). The results herein suggest that the use of mixed surfactant systems
      for the solubilization of polar molecules in environmental remediation
      technologies may be very limited in scope, without clear advantages over the use
      of single surfactant systems. 

PMID- 26311581
TI  - Review on environmental alterations propagating from aquatic to terrestrial
      ecosystems.
AB  - Terrestrial inputs into freshwater ecosystems are a classical field of
      environmental science. Resource fluxes (subsidy) from aquatic to terrestrial
      systems have been less studied, although they are of high ecological relevance
      particularly for the receiving ecosystem. These fluxes may, however, be impacted
      by anthropogenically driven alterations modifying structure and functioning of
      aquatic ecosystems. In this context, we reviewed the peer-reviewed literature for
      studies addressing the subsidy of terrestrial by aquatic ecosystems with special
      emphasis on the role that anthropogenic alterations play in this water-land
      coupling. Our analysis revealed a continuously increasing interest in the
      coupling of aquatic to terrestrial ecosystems between 1990 and 2014 (total: 661
      studies), while the research domains focusing on abiotic (502 studies) and biotic
      (159 studies) processes are strongly separated. Approximately 35% (abiotic) and
      25% (biotic) of the studies focused on the propagation of anthropogenic
      alterations from the aquatic to the terrestrial system. Among these studies,
      hydromorphological and hydrological alterations were predominantly assessed,
      whereas water pollution and invasive species were less frequently investigated.
      Less than 5% of these studies considered indirect effects in the terrestrial
      system e.g. via food web responses, as a result of anthropogenic alterations in
      aquatic ecosystems. Nonetheless, these very few publications indicate far
      reaching consequences in the receiving terrestrial ecosystem. For example, bottom
      up mediated responses via soil quality can cascade over plant communities up to
      the level of herbivorous arthropods, while top-down mediated responses via
      predatory spiders can cascade down to herbivorous arthropods and even plants.
      Overall, the current state of knowledge calls for an integrated assessment on how
      these interactions within terrestrial ecosystems are affected by propagation of
      aquatic ecosystem alterations. To fill these gaps, we propose a scientific
      framework, which considers abiotic and biotic aspects based on an
      interdisciplinary approach. 

PMID- 26311583
TI  - Long-term sub-lethal effects of low concentration commercial herbicide
      (glyphosate/pelargonic acid) formulation in Bryophyllum pinnatum.
AB  - Potential long-term (~7months) sub-lethal impacts of soil-applied low levels of
      Roundup herbicide formulation were investigated in a greenhouse environment using
      the vegetative clones of succulent non-crop plant model, Bryophyllum pinnatum
      (Lam.) Oken. An eleven day LC50 (concentration that killed 50% of the plants) was
      found to be 6.25% (~1.25mg glyphosate/mL and 1.25mg pelargonic acid/mL combined),
      and complete mortality occurred at 12.5%, of the field application rate (i.e.,
      ~20mg glyphosate/mL and 20mg pelargonic acid/mL as active ingredients). While sub
      lethal Roundup (1-5%) exposures led to hormesis-characterized by a significant
      increase in biomass and vegetative reproduction, higher concentrations (>=6.25%)
      were toxic. A significant interaction between Roundup concentrations and leaf
      biomass was found to influence the F1 plantlets' biomass. Biomass asymmetry
      generally increased with increasing Roundup concentrations, indicating that
      plants were more stressed at higher Roundup treatments but within the low-dose
      regime (<=5% of the as-supplied formulation). While leaf apex region demonstrated
      higher reproduction with lower biomass increase, leaf basal area showed lower
      reproduction with greater biomass increase, in plantlets. The results suggest
      long-term exposures to drifted low levels of Roundup in soil may promote biomass
      and reproduction in B. pinnatum. 

PMID- 26311584
TI  - Modeling suspended sediment transport and assessing the impacts of climate change
      in a karstic Mediterranean watershed.
AB  - Mediterranean semi-arid watersheds are characterized by a climate type with long
      periods of drought and infrequent but high-intensity rainfalls. These factors
      lead to the formation of temporary flow tributaries which present flashy
      hydrographs with response times ranging from minutes to hours and high erosion
      rates with significant sediment transport. Modeling of suspended sediment
      concentration in such watersheds is of utmost importance due to flash flood
      phenomena, during which, large quantities of sediments and pollutants are carried
      downstream. The aim of this study is to develop a modeling framework for
      suspended sediment transport in a karstic watershed and assess the impact of
      climate change on flow, soil erosion and sediment transport in a hydrologically
      complex and intensively managed Mediterranean watershed. The Soil and Water
      Assessment Tool (SWAT) model was coupled with a karstic flow and suspended
      sediment model in order to simulate the hydrology and sediment yield of the
      karstic springs and the whole watershed. Both daily flow data (2005-2014) and
      monthly sediment concentration data (2011-2014) were used for model calibration.
      The results showed good agreement between observed and modeled values for both
      flow and sediment concentration. Flash flood events account for 63-70% of the
      annual sediment export depending on a wet or dry year. Simulation results for a
      set of IPCC "A1B" climate change scenarios suggested that major decreases in
      surface flow (69.6%) and in the flow of the springs (76.5%) take place between
      the 2010-2049 and 2050-2090 time periods. An assessment of the future ecological
      flows revealed that the frequency of minimum flow events increases over the
      years. The trend of surface sediment export during these periods is also
      decreasing (54.5%) but the difference is not statistically significant due to the
      variability of the sediment. On the other hand, sediment originating from the
      springs is not affected significantly by climate change. 

PMID- 26311586
TI  - Long Term Results of Visual Field Progression Analysis in Open Angle Glaucoma
      Patients Under Treatment.
AB  - PURPOSE: To evaluate visual field progression with trend and event analysis in
      open angle glaucoma patients under treatment. MATERIALS AND METHODS: Fifteen year
      follow-up results of 408 eyes of 217 glaucoma patients who were followed at Adnan
      Menderes University, Department of Ophthalmology between 1998 and 2013 were
      analyzed retrospectively. Visual field data were collected for Mean Deviation
      (MD), Visual Field Index (VFI), and event occurrence. RESULTS: There were 146
      primary open-angle glaucoma (POAG), 123 pseudoexfoliative glaucoma (XFG) and 139
      normal tension glaucoma (NTG) eyes. MD showed significant change in all
      diagnostic groups (p<0.001). The difference of VFI between first and last
      examinations were significantly different in POAG (p<0.001), and XFG (p<0.003)
      but not in NTG. VFI progression rates were -0.3, -0.43, and -0.2 % loss/year in
      treated POAG, XFG, and NTG, respectively. The number of empty triangles were
      statistically different between POAG-NTG (p=0.001), and XFG-NTG (p=0.002) groups.
      The number of half-filled (p=0.002), and full-filled (p=0.010) triangles were
      significantly different between XFG-NTG groups. CONCLUSION: Functional long-term
      follow-up of glaucoma patients can be monitored with visual field indices. We
      herein report our fifteen year follow-up results in open angle glaucoma.

PMID- 26311585
TI  - Assessing human exposure and odor detection during showering with crude 4
      (methylcyclohexyl)methanol (MCHM) contaminated drinking water.
AB  - In 2014, crude (4-methylcyclohexyl)methanol (MCHM) spilled, contaminating the
      drinking water of 300,000 West Virginians and requiring "do not use" orders to
      protect human health. When the spill occurred, known crude MCHM physicochemical
      properties were insufficient to predict human inhalation and ingestion exposures.
      Objectives are (1) determine Henry's Law Constants (HLCs) for 4-MCHM isomers at
      7, 25, 40, and 80 degrees C using gas chromatography; (2) predict air
      concentrations of 4-MCHM and methyl-4-methylcyclohexanecarboxylate (MMCHC) during
      showering using an established shower model; (3) estimate human ingestion and
      inhalation exposure to 4-MCHM and MMCHC; and (4) determine if predicted air 4
      MCHM exceeded odor threshold concentrations. Dimensionless HLCs of crude cis- and
      trans-4-MCHM were measured to be 1.42*10(-4)+/-6% and 3.08*10(-4)+/-3% at 25
      degrees C, respectively, and increase exponentially with temperature as predicted
      by the van't Hoff equation. Shower air concentrations for cis- and trans-4-MCHM
      are predicted to be 0.089 and 0.390ppm-v respectively after 10min, exceeding the
      US EPA's 0.01ppm-v air screening level during initial spill conditions. Human
      exposure doses were predicted using measured drinking water and predicted shower
      air concentrations and found to greatly exceed available guidance levels in the
      days directly following the spill. Odors would be rapidly detected by 50% of
      individuals at aqueous concentrations below analytical gas chromatographic
      detection limits. MMCHC, a minor odorous component (0.935%) of crude MCHM, is
      also highly volatile and therefore is predicted to contribute to inhalation
      exposures and odors experienced by consumers. 

PMID- 26311587
TI  - Body mass index and socioeconomic position are associated with 9-year
      trajectories of multimorbidity: A population-based study.
AB  - Multimorbidity is a growing public health problem and is more common in women
      than men. However, little is known about multimorbidity trajectories, in terms of
      the accumulation of disease over time, or about the determinants of these
      trajectories. We sought to identify lifestyle and socioeconomic factors related
      to multimorbidity trajectories in mid-aged women. Participants were from the
      Australian Longitudinal Study on Women's Health, a nationally representative
      population-based study. We included 4865 women born 1946-51, without chronic
      disease in 1998, followed triennially for 12 years. We used latent class growth
      analysis to identify 9-year multimorbidity trajectories and multinomial
      regression to calculate relative risk ratios (RRRs) for associations between
      baseline lifestyle and socioeconomic factors and trajectories. We identified five
      multimorbidity trajectories: 'no morbidity, constant'; 'low morbidity, constant';
      'moderate morbidity, constant'; 'no morbidity, increasing'; and 'low morbidity,
      increasing'. Overweight and obesity were associated with an increased risk of the
      'no morbidity, increasing' (RRR 1.70, 95% CI 1.16 to 2.50 and 2.69, 95% CI 1.69
      to 4.28, respectively) and the 'low morbidity, increasing' (RRR 2.57, 95% CI 1.56
      to 4.24 and 4.28, 95% CI 2.41 to 7.60, respectively) trajectories, as compared to
      the 'no morbidity, constant' group. Low education and difficulty managing on
      income were also associated with trajectories of poorer health. Among mid-aged
      women, overweight/obesity and lower socioeconomic status are major risk factors
      for trajectories characterised by accumulation of chronic disease. These
      highlight key target areas for preventive approaches aimed at reducing the risk
      of accumulation of morbidities in mid-aged women.

PMID- 26311588
TI  - A single-arm phase II trial of combined chemotherapy with S-1, oral leucovorin,
      and bevacizumab in heavily pre-treated patients with metastatic colorectal
      cancer.
AB  - BACKGROUND: The mean 5-6-month survival after failed standard chemotherapy for
      metastatic colorectal cancer (mCRC) necessitates more effective treatments for
      refractory mCRC. For untreated mCRC, S-1 + oral leucovorin (SL) therapy offers
      promising results without severe toxicity. The ML18147 trial demonstrated that
      bevacizumab (Bev) prolongs overall survival after mCRC progression. We conducted
      a single-centre phase-II trial to evaluate the safety and efficacy of SL/Bev
      combination chemotherapy as mCRC salvage therapy. METHODS: Major eligibility
      criteria were confirmed adenocarcinoma diagnosis; age >20 years; Eastern
      Cooperative Oncology Group performance status, 0-2; and progression after
      administration/intolerance of/to approved drugs for mCRC. (5-FU, oxaliplatin,
      irinotecan, Bev, and anti-EGFR antibody, if KRAS wild-type). S-1 (80-120 mg/body)
      and leucovorin (25 mg) were orally administered in a 1-week-on/1-week-off
      schedule. Bev (5 mg/kg) was administered on day 1 of every 2-week cycle. The
      primary endpoint was disease control rate (DCR). RESULTS: A total of 31 patients
      were enrolled. DCR was 65% [95% confidence interval (CI), 48-100%] and the
      response rate was 7% (95% CI, 0.7-22%). One patient showing partial response to
      SL/Bev had a BRAF-mutant tumor. Median progression-free survival and overall
      survivals were 5.3 [95% CI, 2.1-9.3] and 9.9 [95% CI, 7.4-NA] months,
      respectively. The most-frequent grade-3/4 adverse events were mucositis (26%) and
      diarrhea (11%), which were manageable by dose reduction/interruption.
      CONCLUSIONS: SL/Bev showed impressive activity in refractory mCRC and was
      tolerable, suggesting its potential as an alternative chemotherapy for refractory
      mCRC. TRIAL REGISTRATION: This study has been registered in University Hospital
      Medical Information Network (UMIN) Clinical Trials Registry ( ID UMIN000009083 )
      on 11 October 2012.

PMID- 26311589
TI  - Efficiently photo-charging lithium-ion battery by perovskite solar cell.
AB  - Electric vehicles using lithium-ion battery pack(s) for propulsion have recently
      attracted a great deal of interest. The large-scale practical application of
      battery electric vehicles may not be realized unless lithium-ion batteries with
      self-charging suppliers will be developed. Solar cells offer an attractive option
      for directly photo-charging lithium-ion batteries. Here we demonstrate the use of
      perovskite solar cell packs with four single CH3NH3PbI3 based solar cells
      connected in series for directly photo-charging lithium-ion batteries assembled
      with a LiFePO4 cathode and a Li4Ti5O12 anode. Our device shows a high overall
      photo-electric conversion and storage efficiency of 7.80% and excellent cycling
      stability, which outperforms other reported lithium-ion batteries, lithium-air
      batteries, flow batteries and super-capacitors integrated with a photo-charging
      component. The newly developed self-chargeable units based on integrated
      perovskite solar cells and lithium-ion batteries hold promise for various
      potential applications. 

PMID- 26311590
TI  - The MR2: A multi-racial, mega-resolution database of facial stimuli.
AB  - Faces impart exhaustive information about their bearers, and are widely used as
      stimuli in psychological research. Yet many extant facial stimulus sets have
      substantially less detail than faces encountered in real life. In this paper, we
      describe a new database of facial stimuli, the Multi-Racial Mega-Resolution
      database (MR2). The MR2 includes 74 extremely high resolution images of European,
      African, and East Asian faces. This database provides a high-quality, diverse,
      naturalistic, and well-controlled facial image set for use in research. The MR2
      is available under a Creative Commons license, and may be accessed online.

PMID- 26311591
TI  - Organic Charge Carriers for Perovskite Solar Cells.
AB  - The photovoltaic field is currently experiencing the "perovskite revolution".
      These materials have been known for decades, but only recently have they been
      applied in solid-state solar cells to obtain outstanding power conversion
      efficiencies. Given that the variety of perovskites used so far is limited, a lot
      of attention has been devoted to the development of suitable organic charge
      transport materials to improve device performance. In this article, we will focus
      on the most promising materials able to transport electrons or holes from a
      structural point of view. Thereby, we focus on organic materials owing to their
      ease of preparation and manipulation, and this is nicely combined with the
      potential tuning of their properties through chemical synthesis. 

PMID- 26311592
TI  - Hepatology and Nephrology: Nimbus.

PMID- 26311593
TI  - Nephrohepatology: Managing the Nexus of Liver and Kidney Interactions.

PMID- 26311595
TI  - Glomerular Diseases Associated With Hepatitis B and C.
AB  - Infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) are prevalent
      worldwide. In this review, we discuss the epidemiology, pathogenesis, clinical
      manifestations, and treatment of HBV- and HCV-related glomerulonephritis (GN).
      The most common histopathologic presentation of HBV-GN is HBV-associated
      membranous nephropathy, which usually manifests clinically with varying grades of
      proteinuria and microscopic hematuria. The pathogenesis is likely to be immune
      complex mediated; however, other host and viral factors have been implicated. The
      treatment of HBV-GN revolves around antiviral therapy. Various histologic types
      of glomerular diseases are reported in association with HCV infection, the most
      frequent being Type 1 membranoproliferative glomerulonephritis, usually in the
      context of Type 2 mixed cryoglobulinemia. The pathogenesis of HCV-GN can be
      attributed to glomerular deposition of cryoglobulins or noncryoglobulin-immune
      complexes. Cryoglobulins typically comprised immunoglobulin Mkappa with
      rheumatoid factor activity. Clinically, patients may present with proteinuria,
      microscopic hematuria, hypertension, and acute nephritic and/or nephrotic
      syndrome. The treatment of HCV-GN, especially cryoglobulinemic
      membranoproliferative glomerulonephritis, encompasses various options including
      contemporary antiviral therapy with or without conventional and novel
      immunomodulatory agents. 

PMID- 26311594
TI  - GFR Estimating Equations and Liver Disease.
AB  - It is important to accurately assess the glomerular filtration rate (GFR) of
      patients with liver disease to deliver care and allocate organs for
      transplantation in a way that improves outcomes. The most commonly used methods
      to estimate GFR in this population are based on creatinine, which is biased by
      these patients' low creatinine production and potentially by elevated serum
      bilirubin and decreased albumin levels. None of the creatinine-based estimated
      glomerular filtration rate (eGFR) equations have been specifically modified for a
      population with liver disease, and even measurement of a 24-hour creatinine
      clearance has limitations. In liver disease, all creatinine-based estimates of
      GFR overestimate gold standard-measured GFR, and the degree of overestimation is
      highest at lower measured GFR values and in more severe liver disease. Cystatin C
      based eGFR has shown promise in general population studies by demonstrating less
      bias than creatinine-based eGFR and improved association with clinically
      important outcomes, but results in the liver disease population have been mixed,
      and further studies are necessary. Ultimately, specific eGFR equations for liver
      disease or novel methods for estimating GFR may be necessary. However, for now,
      the limitations of currently available methods need to be appreciated to
      understand kidney function in liver disease. 

PMID- 26311596
TI  - Current Management of Chronic Hepatitis B and C in Chronic Kidney Disease.
AB  - The landscape of therapeutic options for hepatitis B and C has changed
      drastically over the course of 2 decades. There are now novel, effective, well
      tolerated, oral antiviral agents being used to successfully control chronic
      hepatitis B (HBV) infections and cure chronic hepatitis C (HCV) infections.
      However, patients with CKD were rarely included in the Phase II and III
      randomized trials for these medications. This paucity of data and the high
      prevalence of comorbidities associated with CKD pose distinct challenges to
      physicians treating chronic hepatitis B virus and hepatitis C virus infections in
      the setting of kidney insufficiency/failure. Thus, this review will attempt to
      summarize the current data regarding novel antiviral therapies for HBV and HCV in
      the CKD population. 

PMID- 26311597
TI  - Hyponatremia in Cirrhosis--Pathogenesis, Treatment, and Prognostic Significance.
AB  - Cirrhosis is characterized by systemic and splanchnic vasodilation that leads to
      excessive nonosmotic secretion of vasopressin (antidiuretic hormone).
      Hyponatremia is a common electrolyte abnormality in advanced liver disease that
      results from the impaired ability of the kidney to excrete solute-free water that
      leads to "dilutional" hyponatremia-water retention disproportionate to the
      retention of sodium. Hyponatremia in liver diseases carries the prognostic
      burden, correlates with the severity of cirrhosis, and, in recent studies, has
      also been implicated in the pathogenesis of hepatic encephalopathy. The current
      treatment options are limited to conventional therapies like fluid restriction,
      and the outcomes are unsatisfactory. Although currently available vasopressin (V2
      receptors) antagonists have been shown to increase serum sodium concentrations
      and improve ascites control, their role in the treatment of hyponatremia in liver
      disease patients remains questionable because of adverse effect profiles, high
      cost, and poor data on long-term mortality benefits. More information is needed
      to argue the benefits vs risks of short-term use of vaptans for correction of
      hyponatremia especially just hours-to-days before liver transplant. 

PMID- 26311598
TI  - Acute Kidney Injury in Liver Disease: Role of Biomarkers.
AB  - Acute kidney injury (AKI) is a common complication in patients with advanced
      cirrhosis and is associated with significant mortality. The most common
      etiologies of AKI in this setting are prerenal azotemia, acute tubular necrosis,
      and hepatorenal syndrome. Despite the overall poor outcomes of patients with
      cirrhosis and AKI, potentially efficacious therapies exist but must be tailored
      to the specific AKI etiology. Unfortunately, determining the etiology of AKI in
      the setting of cirrhosis is notoriously difficult. Many of the standard
      diagnostic tools, such as urine microscopy and the fractional excretion of
      sodium, have traditionally been ineffective. Novel biomarkers of kidney tubular
      injury may be able to assist with differential diagnosis and the appropriate
      targeting of treatments by distinguishing structural from functional causes of
      AKI. In recent studies, both urinary neutrophil gelatinase-associated lipocalin
      and interleukin-18 have shown the ability to distinguish hepatorenal syndrome
      from prerenal azotemia and acute tubular necrosis. In addition, multiple
      biomarkers, including neutrophil gelatinase-associated lipocalin and interleukin
      18, have demonstrated the ability to independently predict both progression of
      AKI and mortality. Critically, recent research also indicated that commonly
      available tests, fractional excretion of sodium and proteinuria, may also be able
      to distinguish etiologies of AKI in cirrhosis, but diagnostic cutoffs must be re
      conceptualized specifically to this unique AKI setting. 

PMID- 26311599
TI  - What a Nephrologist Needs to Know About Acute Liver Failure.
AB  - Although relatively rare in the United States, acute liver failure (ALF) is
      associated with very high rates of morbidity and mortality. A leading cause of
      morbidity and mortality is cerebral edema and intracranial hypertension.
      Hypothermia, osmotic diuretics, and hyperosmolar therapy are commonly used to
      manage these complications; however, when these are ineffective, renal
      replacement therapy may be needed for volume management. Acute kidney injury is a
      common complication of ALF and may arise from a number of etiologies, including
      hepatorenal syndrome and acute tubular necrosis. Acute kidney injury is most
      common in patients who develop ALF because of acetaminophen toxicity or ischemia.
      With regard to renal replacement therapy, we will review specific considerations
      relevant to the management of the patient with ALF. 

PMID- 26311600
TI  - Albumin Dialysis for Liver Failure: A Systematic Review.
AB  - Albumin dialysis is the best-studied extracorporeal nonbiologic liver support
      system as a bridge or destination therapy for patients with liver failure
      awaiting liver transplantation or recovery of liver function. We performed a
      systematic review to examine the efficacy and safety of 3 albumin dialysis
      systems (molecular adsorbent recirculating system [MARS], fractionated plasma
      separation, adsorption and hemodialysis [Prometheus system], and single-pass
      albumin dialysis) in randomized trials for supportive treatment of liver failure.
      PubMed, Ovid, EMBASE, Cochrane's Library, and ClinicalTrials.gov were searched.
      Two authors independently screened citations and extracted data on patient
      characteristics, quality of reports, efficacy, and safety end points. Ten trials
      (7 of MARS and 3 of Prometheus) were identified (620 patients). By meta-analysis,
      albumin dialysis achieved a net decrease in serum total bilirubin level relative
      to standard medical therapy of 8.0 mg/dL (95% confidence interval [CI], -10.6 to 
      5.4) but not in serum ammonia or bile acids. Albumin dialysis achieved an
      improvement in hepatic encephalopathy relative to standard medical therapy with a
      risk ratio of 1.55 (95% CI, 1.16-2.08) but had no effect survival with a risk
      ratio of 0.95 (95% CI, 0.84-1.07). Because of inconsistency in the reporting of
      adverse events, the safety analysis was limited but did not demonstrate major
      safety concerns. Use of albumin dialysis as supportive treatment for liver
      failure is successful at removing albumin-bound molecules, such as bilirubin and
      at improving hepatic encephalopathy. Additional experience is required to guide
      its optimal use and address safety concerns. 

PMID- 26311602
TI  - Simultaneous Liver-Kidney Transplant: Too Many or Just Enough?
AB  - For liver transplant candidates with advanced kidney dysfunction, simultaneous
      liver-kidney (SLK) transplantation is an important option. As the incidence of
      severe kidney dysfunction has increased over the past decade, so have the numbers
      of SLK transplants. This has engendered controversy within the transplant
      community because SLK transplants draw deceased donor kidneys from the kidney
      transplant candidate pool. Because kidney recovery after liver transplant alone
      (LTA) is difficult to predict, indications for SLK are not precisely defined.
      Candidates with hepatorenal syndrome can have kidney recovery after as much as 12
      weeks on dialysis, whereas those with CKD may have early ESRD after LTA because
      of perioperative events and calcineurin inhibitor exposure. Although large
      observational studies generally show slightly improved survival in SLK recipients
      compared with LTA, inferences from these studies are limited by selection biases.
      Therefore, a true survival benefit of SLK in candidates without ESRD is still
      unproved. Although selection practices vary, generally LTA candidates have more
      kidney dysfunction because of hepatorenal syndrome and acute kidney injury,
      whereas SLK candidates have less severe liver disease and more CKD or ESRD. The
      debate over appropriate SLK is primarily one of the optimal kidney utilization vs
      the best interests of individual liver transplant candidates. 

PMID- 26311601
TI  - Kidney Failure and Liver Allocation: Current Practices and Potential
      Improvements.
AB  - In February 2002, the United Network for Organ Sharing implemented a system for
      prioritizing candidates for liver transplantation that was based on the risk of
      90-day mortality as determined by the Model for End-Stage Liver Disease (MELD)
      score. As the MELD score is driven in part by serum creatinine as a marker of
      kidney function, the prevalence of kidney dysfunction and failure in patients
      with end-stage liver disease at the time of listing and at transplantation has
      steadily risen. In this review, we discuss current practices in liver
      transplantation in patients with kidney dysfunction focusing briefly on the
      decision to perform simultaneous liver-kidney transplantation. We then discuss
      pitfalls to the current practices of liver transplantation in patients with
      kidney dysfunction. We conclude by discussing potential improvements to current
      practices including the use of the MELD-Na score, alternatives to creatinine and
      creatinine-based equation for estimating kidney function, and the use of
      intraoperative kidney replacement therapy during liver transplantation. 

PMID- 26311603
TI  - Chronic Kidney Disease and Related Long-Term Complications After Liver
      Transplantation.
AB  - Liver transplantation is the standard of care for patients with decompensated
      cirrhosis. Liver transplantation recipients have excellent short-term and long
      term outcomes including patient and graft survival. Since the adoption of model
      for end-stage liver disease (MELD)-based allocation policy, the incidence of post
      transplant end stage renal disease has risen significantly. Occurrence of Stage 4
      chronic kidney disease and end stage renal disease substantially increases the
      risk of post-transplant deaths. Because majority of late post-transplant
      mortality is due to nonhepatic post-transplant comorbidities, personalized care
      directed toward risk factor modification may further improve post-transplant
      survival. 

PMID- 26311604
TI  - Neuroanatomical correlates of personality in chimpanzees (Pan troglodytes):
      Associations between personality and frontal cortex.
AB  - Converging empirical data suggests that a set of largely consistent personality
      traits exist in both human and nonhuman primates; despite these similarities,
      almost nothing is known concerning the neurobiological basis of these traits in
      nonhuman primates. The current study examined associations between chimpanzee
      personality traits and the grey matter volume and asymmetry of various frontal
      cortex regions in 107 captive chimpanzees. Chimpanzees rated as higher on
      Openness and Extraversion had greater bilateral grey matter volumes in the
      anterior cingulate cortex. Further, chimpanzee rated as higher on Dominance had
      larger grey volumes in the left anterior cingulate cortex and right Prefrontal
      Cortex (PFC). Finally, apes rated higher on Reactivity/Unpredictability had
      higher grey matter volumes in the right mesial PFC. All associations survived
      after applying False Discovery Rate (FDR) thresholds. Results are discussed in
      terms of current neuroscientific models of personality which suggest that the
      frontal cortex, and asymmetries in this region, play an important role in the
      neurobiological foundation of broad dispositional traits. 

PMID- 26311605
TI  - Cognitive neuroscience neuroimaging repository for the adult lifespan.
AB  - With recent advances in neuroimaging technology, it is now possible to image
      human brain function in vivo, which revolutionized the cognitive neuroscience
      field. However, like any other newly developed technique, the acquisition of
      neuroimaging data is costly and logistically challenging. Furthermore, studying
      human cognition requires acquiring a large amount of neuroimaging data, which
      might not be feasible to do by every researcher in the field. Here, we describe
      our group's efforts to acquire one of the largest neuroimaging datasets that aims
      to investigate the neural substrates of age-related cognitive decline, which will
      be made available to share with other investigators. Our neuroimaging repository
      includes up to 14 different functional images for more than 486 subjects across
      the entire adult lifespan in addition to their 3 structural images. Currently,
      data from 234 participants have been acquired, including all 14 functional and 3
      structural images, which is planned to increased to 375 participants in the next
      few years. A complete battery of neuropsychological tests was also administered
      to all participants. The neuroimaging and accompanying psychometric data will be
      available through an online and easy-to-use data sharing website.

PMID- 26311606
TI  - Connected brains and minds--The UMCD repository for brain connectivity matrices.
AB  - We describe the USC Multimodal Connectivity Database
      (http://umcd.humanconnectomeproject.org), an interactive web-based platform for
      brain connectivity matrix sharing and analysis. The site enables users to
      download connectivity matrices shared by other users, upload matrices from their
      own published studies, or select a specific matrix and perform a real-time graph
      theory-based analysis and visualization of network properties. The data shared on
      the site span a broad spectrum of functional and structural brain connectivity
      information from humans across the entire age range (fetal to age 89),
      representing an array of different neuropsychiatric and neurodegenerative disease
      populations (autism spectrum disorder, ADHD, and APOE-4 carriers). An analysis
      combining 7 different datasets shared on the site illustrates the diversity of
      the data and the potential for yielding deeper insight by assessing new
      connectivity matrices with respect to population-wide network properties
      represented in the UMCD. 

PMID- 26311607
TI  - Complex sensorimotor transformation processes required for response selection are
      facilitated by the striatum.
AB  - Both fronto-parietal networks and the basal ganglia play an important role in
      action cascading. It is well-known that cortical structures mediate sensorimotor
      transformation for this purpose. The striatum receives extensive input from those
      cortical structures and has been shown to be modulated by the predictability of
      cortical input. Until today, it has however remained unclear whether the
      processing of spatial codes or even sensorimotor transformation processes for the
      purpose of action cascading involve the striatum. We therefore examined this
      question by means of fMRI using a stop-change task that varied the predictability
      as well as the complexity of sensorimotor transformations required for correct
      responding in the context of action cascading. On the behavioral level, we found
      that the complexity of sensorimotor transformation processes only prolonged
      reaction times when the requirement for this transformation was predictable. fMRI
      results matched this effect showing enhanced activity of the caudate in case a
      complex sensorimotor transformation could be anticipated. Irrespective of the
      complexity of the required transformations, the putamen was furthermore involved
      in the prediction of imminent action cascading demands. Taken together, our
      findings give rise to a conceptual advance regarding basal ganglia function by
      showing that the anticipation and, more importantly, processing of complex
      sensorimotor transformation processes involves the striatum. 

PMID- 26311608
TI  - A subset of ocular adnexal marginal zone lymphomas may arise in association with
      IgG4-related disease.
AB  - We previously suggested a relationship between ocular immunoglobulin (Ig)G4
      related disease (IgG4-RD) and marginal zone lymphomas (MZLs). However, the
      cytokine background associated with these disorders and whether it differs
      between ocular adnexal MZLs with (IgG4-associated MZL) and without (IgG4-negative
      MZL) numerous IgG4(+) plasma cells are unknown. In this study, we identified the
      mRNA expression pattern of Th2 and regulatory T-cell (Treg) cytokines in IgG4-RD
      and in IgG4-associated MZL and IgG4-negative MZL using real-time polymerase chain
      reaction analysis. Ocular IgG4-RD and IgG4-associated MZL exhibited significantly
      higher expression ratios of interleukin (IL)-4/beta-actin, IL-10/beta-actin, IL
      13/beta-actin, transforming growth factor (TGF) beta1/beta-actin, and FOXP3/beta
      actin than did IgG4-negative MZL (p < 0.05). This finding further supports our
      prior observations that a significant subset of ocular MZLs arises in the setting
      of IgG4-RD. Furthermore, the presence of a different inflammatory background in
      IgG4-negative MZLs suggests that IgG4-associated MZLs may have a different
      pathogenesis. 

PMID- 26311609
TI  - Association of the relative change in weight and body mass index with lung
      function in teenagers and adults with cystic fibrosis: Influence of gender and
      diabetes.
AB  - BACKGROUND: Nutritional status is a prognostic factor in cystic fibrosis.
      Prevention of nutritional impairment and weigh loss are major clinical objectives
      because they are associated with worsening of lung function and increased
      mortality. OBJECTIVE: To identify a potential relationship of clinical nutrition
      parameters, and their relative changes, with lung function (FEV1%) in a cohort of
      adolescent and adult patients with CF. METHODS: A retrospective analysis of 64
      patients older than 14years. Weight, height, BMI, and lung function data were
      collected at a period of disease stability, both in the year of the first
      abnormal oral glucose tolerance test (OGTT) and in the previous year. Relative
      changes in weight and BMI, and their relationship with FEV1%, were determined by
      linear regression and ANOVA tests; influence of gender and diabetes was also
      assessed. RESULTS: Mean age of the series (28 females and 36 males) was
      26.8years. Normal glucose tolerance (NGT) was found in 26.7%, while 18.3% had
      diabetes without impaired fasting glucose (CFRD without FPG). Mean BMI was 20.32,
      with a mean weight of 53.53kg; 32.8% had BMI<18.5, and only 4.7% were overweight.
      Overall, a positive relative change in weight (>=6%) was associated with an
      increase in FEV1% (9.31%), as compared to those with a greater weight loss (at
      least 2%), who had a 12.09% fall in FEV1. Patients with CFRD without FPG had
      poorer lung function if they had a negative relative change in weight by at least
      2% as compared to NGT. CONCLUSIONS: In patients with CF, a relative weight gain
      is positively associated to FEV1%, while a relative weight loss of at least 2%
      has a significant negative impact on lung function.

PMID- 26311610
TI  - Pancytopenia in the first trimester: An indicator of hidden hyperthyroidism.
AB  - Pancytopenia in the first trimester is very rare. A 33-year-old multiparous woman
      presented with nausea, loss of appetite, and bodyweight loss of 7.4 kg at 9(1/7)
      weeks of gestation due to hyperemesis gravidarum. Her laboratory data
      demonstrated pancytopenia involving white blood cell count of 3500/MUL, a
      hemoglobin level of 9.8 g/dL, and a platelet count of 10.5 * 10(4)/MUL. An
      extensive investigation into the causes of the pancytopenia detected true
      hyperthyroidism: thyroid-stimulating hormone, <0.02 MUU/mL; free
      triiodothyronine, 11.25 pg/mL; free thyroxine, 4.74 ng/dL; and anti-thyroid
      stimulating hormone receptor antibodies, 12.2 IU/L. Propylthiouracil was started
      at a dose of 300 mg/day at 10(5/7) weeks of gestation, which resulted in the
      normalization of her blood parameters and concomitant improvements in her free
      triiodothyronine and free thyroxine levels at 12(0/7) weeks of gestation.
      Pancytopenia in the first trimester might be indicative of hidden
      hyperthyroidism.

PMID- 26311611
TI  - Erratum to: Angiotensin-converting enzyme inhibitors of Bothrops jararaca snake
      venom affect the structure of mice seminiferous epithelium.
AB  - [This corrects the article DOI: 10.1186/s40409-015-0030-y.]. 

PMID- 26311612
TI  - Sensitivity of a rapid point of care assay for early HIV antibody detection is
      enhanced by its ability to detect HIV gp41 IgM antibodies.
AB  - BACKGROUND: Anti-HIV-1 IgM antibody is an important immunoassay target for early
      HIV antibody detection. OBJECTIVES: The objective of this study is to determine
      if the early HIV antibody sensitivity of the 60s INSTI test is due to detection
      of anti-HIV-1 IgM in addition to IgG. STUDY DESIGN: To demonstrate HIV gp41 IgM
      antibody capture by the INSTI HIV-1 gp41 recombinant antigen, an HIV-IgM ELISA
      was conducted with commercial HIV-1 seroconversion samples. To demonstrate that
      the INSTI dye-labelled Protein A-based colour developer (CD) has affinity to
      human IgM, commercial preparations of purified human immunoglobulins (IgM, IgD,
      IgA, IgE, and IgG) were blotted onto nitrocellulose (NC) and probed with the CD
      to observe spot development. To determine that INSTI is able to detect anti-HIV-1
      IgM antibody, early seroconversion samples, were tested for reduced INSTI test
      spot intensity following IgM removal. RESULTS: The gp41-based HIV-IgM ELISA
      results for 6 early seroconversion samples that were INSTI positive determined
      that the assay signal was due to anti-HIV-1 IgM antibody capture by the
      immobilised gp41 antigen. The dye-labelled Protein-A used in the INSTI CD
      produced distinct spots for purified IgM, IgA, and IgG blotted on the NC
      membrane. Following IgM removal from 21HIV-1 positive seroconversion samples with
      known or undetermined anti-HIV-1 IgM levels that were western blot negative or
      indeterminate, all samples had significantly reduced INSTI test spot intensity.
      CONCLUSIONS: The INSTI HIV-1/HIV-2 Antibody Test is shown to detect anti-HIV-1
      IgM antibodies in early HIV infection which enhances its utility in early HIV
      diagnosis.

PMID- 26311613
TI  - Comparison of Two Successive Earthquake Awareness Campaigns in Israel: Improved
      Methodology or a Cumulative Effect?
AB  - OBJECTIVES: An effective way to reduce casualties from earthquakes is to increase
      population preparedness. During 2011 to 2013, Israeli authorities executed 3
      national-level earthquake awareness campaigns. We aimed to assess the impact of
      these campaigns on the populace and the ability of the campaigns to produce a
      cumulative effect throughout the study period. METHODS: Two surveys were
      conducted 2 weeks after the end of the first campaign and the third campaign in a
      similar randomly selected representative sample. RESULTS: Exposure to the
      campaign proved to be a significant factor in increasing the knowledge of the
      respondents, giving a knowledge advantage of 1.5 times to respondents exposed to
      the campaign. However, the period of assessment proved to be an even more
      significant factor, with knowledge in 2013 being 2.3 times that in 2011.
      Additionally, a gap of up to 40% between the levels of trust and the perceived
      responsibility of respective authorities in the times of earthquake was found.
      CONCLUSIONS: This study found an improvement in public knowledge regarding
      earthquake preparedness over the 3 years of the study. This may mean that an
      awareness campaign does not stand by itself, but should be part of an integrated
      long-term process in order to have a lasting effect on the population.

PMID- 26311614
TI  - When community reintegration is not the best option: interethnic violence and the
      trauma of parental loss in South Sudan.
AB  - The magnitude of violence and human loss in conflict settings often exceeds the
      caring capacity of traditional support systems for orphans. The aim of this study
      is to understand the developmental context for children experiencing armed
      conflict, parental loss, extreme poverty, violence and social exclusion in a
      setting affected by interethnic violence. This article challenges the received
      wisdom that community reintegration is always better than institutional
      provision. Using a case study employing interviews, focus groups, workshops and
      observations, we examined how children's experiences of armed violence and
      parental loss affected their mental well-being, and their relationships within
      their community. Emerging findings such as experienced violence and psychological
      distress were further investigated using a cross-sectional survey design to
      explore the generalisability or transferability of theories or conclusions drawn
      from qualitative data. Findings showed that parental loss had a major impact on
      children's lives in the context of armed violence. Four main outcomes of
      orphanhood emerged: (i) facing the situation and evading harm (feelings of
      rejection and stigmatisation); (ii) trauma exposure and mental health effects
      (associations of orphanhood with adverse mental health outcomes and the number
      and type of experienced trauma); (iii) dealing with psychological distress
      (seeking caring connections and decreased feelings of isolation); and (iv)
      education and acceptance (increasing knowledge, skills and attitude and being
      respected in their community). We discuss the role that contexts such as armed
      violence, parental loss and social exclusion play for children's mental well
      being and their implications for psychosocial interventions and orphan care in
      humanitarian settings. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 26311615
TI  - Early-life house dust mite allergens, childhood mite sensitization, and
      respiratory outcomes.

PMID- 26311616
TI  - A Novel Methodology to Synthesize Highly Conductive Anion Exchange Membranes.
AB  - Alkaline polyelectrolyte fuel cell now receives growing attention as a promising
      candidate to serve as the next generation energy-generating device by enabling
      the use of non-precious metal catalysts (silver, cobalt, nickel et al.). However,
      the development and application of alkaline polyelectrolyte fuel cell is still
      blocked by the poor hydroxide conductivity of anion exchange membranes. In order
      to solve this problem, we demonstrate a methodology for the preparation of highly
      OH(-) conductive anion exchange polyelectrolytes with good alkaline tolerance and
      excellent dimensional stability. Polymer backbones were grafted with flexible
      aliphatic chains containing two or three quaternized ammonium groups. The highly
      flexible and hydrophilic multi-functionalized side chains prefer to aggregate
      together to facilitate the formation of well-defined hydrophilic-hydrophobic
      microphase separation, which is crucial for the superior OH(-) conductivity of 69
      mS/cm at room temperature. Besides, the as-prepared AEMs also exhibit excellent
      alkaline tolerance as well as improved dimensional stability due to their
      carefully designed polymer architecture, which provide new directions to pursue
      high performance AEMs and are promising to serve as a candidate for fuel cell
      technology. 

PMID- 26311617
TI  - COMPARISON BETWEEN MAGNETIC RESONANCE IMAGING ESTIMATES OF EXTRACRANIAL
      CEREBROSPINAL FLUID VOLUME AND PHYSICAL MEASUREMENTS IN HEALTHY DOGS.
AB  - Dosages for myelography procedures in dogs are based on a hypothetical
      proportional relationship between bodyweight and cerebrospinal fluid (CSF)
      volume. Anecdotal radiographic evidence and recent studies have challenged the
      existence of such a defined relationship in dogs. The objectives of this
      prospective cross-sectional study were to describe CSF volumes using magnetic
      resonance imaging (MRI) in a group of clinically healthy dogs, measure the
      accuracy of MRI CSF volumes, and compare MRI CSF volumes with dog physical
      measurements. A sampling perfection with application optimized contrast using
      different flip-angle evolution MRI examination of the central nervous system was
      carried out on 12 healthy, male mongrel dogs, aged between 3 and 5 years with a
      bodyweight range of 7.5-35.0 kg. The images were processed with image analysis
      freeware (3D Slicer) in order to calculate the volume of extracranial CSF.
      Cylindrical phantoms of known volume were included in scans and used to calculate
      accuracy of MRI volume estimates. The accuracy of MRI volume estimates was 99.8%.
      Extracranial compartment CSF volumes ranged from 20.21 to 44.06 ml. Overall
      volume of the extracranial CSF increased linearly with bodyweight, but the
      proportional volume (ml/bodyweight kilograms) of the extracranial CSF was
      inversely proportional to bodyweight. Relative ratios of volumes in the cervical,
      thoracic, and lumbosacral regions were constant. Findings indicated that the
      current standard method of using body weight to calculate dosages of myelographic
      contrast agents in dogs may need to be revised. 

PMID- 26311618
TI  - Health Anxiety in Preadolescence--Associated Health Problems, Healthcare
      Expenditure, and Continuity in Childhood.
AB  - Epidemiological data on the distribution, persistence, and clinical correlates of
      health anxiety (HA) in childhood are scarce. We investigated continuity of HA
      symptoms and associated health problems and medical costs in primary health
      services in a general population birth cohort. HA symptoms were assessed in 1886
      Danish 11-12 year old children (48 % boys) from the Copenhagen Child Cohort using
      the Childhood Illness Attitude Scales (CIAS) together with information on socio
      demographics and the child's somatic and mental status and healthcare
      expenditure. Non-parametric statistics and regression analysis were used to
      compare groups with low (n = 184), intermediate (n = 1539), and high (n = 161) HA
      symptom scores. The association between HA symptoms assessed at age 5-7 years and
      HA symptoms at ages 11-12 years was examined by Stuart-Maxwell test. HA symptoms
      were significantly associated with emotional disorders and unspecific somatic
      complaints, but not with chronic physical conditions. In regression analyses
      controlling for gender and physical comorbidity, healthcare expenditure peaked in
      children with the highest HA symptom score, that is these children used on
      average approximately 150 Euro more than children with the lowest score during
      the 2-year period preceding inclusion. HA symptoms at age 5-7 years were
      significantly associated with HA symptoms at age 11-12 years. We conclude that HA
      symptoms, including hypochondriacal fears and beliefs, were non-trivial in
      preadolescents; they showed continuity from early childhood and association with
      emotional disorders, unspecific somatic complaints, and increased healthcare
      expenditure. Further research in the clinical significance of childhood HA is
      required. 

PMID- 26311619
TI  - Comorbid Development of Disruptive Behaviors from age 11/2 to 5 Years in a
      Population Birth-Cohort and Association with School Adjustment in First Grade.
AB  - Comorbidity is frequent among disruptive behaviors (DB) and leads to mental
      health problems during adolescence and adulthood. However, the early
      developmental origins of this comorbidity have so far received little attention.
      This study investigated the developmental comorbidity of three DB categories
      during early childhood: hyperactivity-impulsivity, non-compliance, and physical
      aggression. Joint developmental trajectories of DB were identified based on
      annual mother interviews from age 11/2 to 5 years, in a population-representative
      birth-cohort (N = 2045). A significant proportion of children (13 % to 21 %,
      depending on the type of DB) consistently displayed high levels of hyperactivity
      impulsivity, non-compliance, or physical aggression from age 11/2 to 5 years.
      Developmental comorbidity was frequent, especially for boys: 10 % of boys and 3.7
      % of girls were on a stable trajectory with high levels of symptoms for the three
      categories of DB. Significant associations were observed between preschool joint
      trajectories of DB and indicators of DB and school adjustment assessed by
      teachers in first grade. Preschoolers who maintained high levels of hyperactivity
      impulsivity, non-compliance, and physical aggression, displayed the highest
      number of DB symptoms in first grade for all categories according to their
      teacher. They were also among the most disadvantaged of their class for school
      adjustment indicators. Thus, DB manifestations and developmental comorbidity of
      DB are highly prevalent in infancy. Early childhood appears to be a critical
      period to prevent persistent and comorbid DB that leads to impairment at the very
      beginning of school attendance and to long-term serious health and social
      adjustment problems. 

PMID- 26311621
TI  - Psychometric evaluation of self-report measures of binge-eating symptoms and
      related psychopathology: A systematic review of the literature.
AB  - OBJECTIVE: Binge eating is a symptom common to bulimia nervosa, anorexia nervosa
      (binge/purge subtype), and binge eating disorder. There are many self-report
      measures available to aid the assessment of eating disorders symptoms, but there
      has not yet been a systematic review of the literature to identify the most valid
      and reliable measures for use in assessment and treatment of binge eating.
      METHOD: A systematic review of the psychometric properties of self-report
      measures that assess binge eating symptoms and psychopathology was conducted. Two
      independent raters assessed the psychometric properties of each measure using a
      standardized quality analysis tool. RESULTS: Of the 2,927 studies identified, 72
      studies met the inclusion criteria and described the psychometric properties of
      29 different self-report measures, and nine specific subscales within these.
      Results from the quality analysis tool utilized in this study indicated that none
      of the included measures currently meet all nine criteria of adequate
      psychometric properties. DISCUSSION: Most of the included measures had evidence
      for some adequate psychometric properties. Two measures received six out of nine
      positive ratings for the assessed psychometric properties, the BITE and the BULIT
      R, and thus appear to be the measures with the most evidence of their validity
      and reliability. Overall, our findings implicate a need for further investigation
      of the psychometric properties of the available self-report questionnaires in
      this field.

PMID- 26311620
TI  - Electron microscopy of human fascia lata: focus on telocytes.
AB  - From the histological point of view, fascia lata is a dense connective tissue.
      Although extracellular matrix is certainly the most predominant fascia's feature,
      there are also several cell populations encountered within this structure. The
      aim of this study was to describe the existence and characteristics of fascia
      lata cell populations viewed through a transmission electron microscope. Special
      emphasis was placed on telocytes as a particular interstitial cell type, recently
      discovered in a wide variety of tissues and organs such as the heart, skeletal
      muscles, skin, gastrointestinal tract, uterus and urinary system. The conducted
      study confirmed the existence of a telocyte population in fascia lata samples.
      Those cells fulfil main morphological criteria of telocytes, namely, the presence
      of very long, thin cell processes (telopodes) extending from a relatively small
      cell body. Aside from telocytes, we have found fibroblasts, mast cells and cells
      with features of myofibroblastic differentiation. This is the first time it has
      been shown that telocytes exist in human fascia. Currently, the exact role of
      those cells within the fascia is unknown and definitely deserves further
      attention. One can speculate that fascia lata telocytes likewise telocytes in
      other organs may be involved in regeneration, homeostasis and intracellular
      signalling. 

PMID- 26311622
TI  - Missense mutations in sodium channel SCN1A and SCN2A predispose children to
      encephalopathy with severe febrile seizures.
AB  - OBJECTIVE: Acute encephalopathy with biphasic seizures and late reduced diffusion
      (AESD) is a childhood encephalopathy following severe febrile seizures. The
      pathogenesis of AESD is considered to be fever-induced seizure susceptibility and
      excitotoxicity, which may be caused by sodium channel dysfunction in some cases.
      Here we studied whether mutations in genes encoding sodium channels, SCN1A and
      SCN2A, predispose children to AESD. METHODS: We recruited 92 AESD patients in a
      nationwide survey of acute encephalopathy in Japan from 2008 to 2011. We
      collected their genomic DNA samples, and sequenced the entire coding region of
      SCN1A and SCN2A. RESULTS: Five out of 92 patients (5.4%) had missense mutations
      either in SCN1A or SCN2A. After a preceding infection with fever, all the
      patients showed status epilepticus at the onset. Hemiconvulsion-hemiplegia was
      recognized in three patients during the acute/subacute phase. One patient had
      taken theophylline for the treatment of bronchial asthma just before the onset of
      AESD. Familial history was not remarkable except one patient with a SCN1A
      mutation (G1647S) whose mother had a similar episode of AESD in her childhood. A
      different substitution (G1674R) at the same amino acid position, as well as two
      other SCN1A mutations found in this study, had previously been reported in Dravet
      syndrome. Another SCN1A mutation (R1575C) had been detected in other types of
      acute encephahlitis/encephalopathy. One patient had SCN2A mutation, F328V, which
      had previously been reported in Dravet syndrome. Another SCN2A mutation, I172V,
      was novel. None of the patients were diagnosed with Dravet syndrome or genetic
      (generalized) epilepsy with febrile seizure plus in the following-up period.
      CONCLUSIONS: Mutations in SCN1A and SCN2A are a predisposing factor of AESD.
      Altered channel activity caused by these mutations may provoke seizures and
      excitotoxic brain damage.

PMID- 26311623
TI  - Mock communities highlight the diversity of host-associated eukaryotes.
AB  - Host-associated microbes are ubiquitous. Every multicellular eukaryote, and even
      many unicellular eukaryotes (protists), hosts a diverse community of microbes.
      High-throughput sequencing (HTS) tools have illuminated the vast diversity of
      host-associated microbes and shown that they have widespread influence on host
      biology, ecology and evolution (McFall-Ngai et al. ). Bacteria receive most of
      the attention, but protists are also important components of microbial
      communities associated with humans (Parfrey et al. ) and other hosts. As HTS
      tools are increasingly used to study eukaryotes, the presence of numerous and
      diverse host-associated eukaryotes is emerging as a common theme across
      ecosystems. Indeed, HTS studies demonstrate that host-associated lineages account
      for between 2 and 12% of overall eukaryotic sequences detected in soil, marine
      and freshwater data sets, with much higher relative abundances observed in some
      samples (Ramirez et al. ; Simon et al. ; de Vargas et al. ). Previous studies in
      soil detected large numbers of predominantly parasitic lineages such as
      Apicomplexa, but did not delve into their origin [e.g. (Ramirez et al. )]. In
      this issue of Molecular Ecology, Geisen et al. () use mock communities to show
      that many of the eukaryotic organisms detected by environmental sequencing in
      soils are potentially associated with animal hosts rather than free-living. By
      isolating the host-associated fraction of soil microbial communities, Geisen and
      colleagues help explain the surprisingly high diversity of parasitic eukaryotic
      lineages often detected in soil/terrestrial studies using high-throughput
      sequencing (HTS) and reinforce the ubiquity of these host-associated microbes. It
      is clear that we can no longer assume that organisms detected in bulk
      environmental sequencing are free-living, but instead need to design studies that
      specifically enumerate the diversity and function of host-associated eukaryotes.
      Doing so will allow the field to determine the role host-associated eukaryotes
      play in soils and other environments and to evaluate hypotheses on assembly of
      host-associated communities, disease ecology and more. 

PMID- 26311624
TI  - Resveratrol: beneficial or not? Opposite effects of resveratrol on hypoxia
      dependent PAI-1 expression in tumour and primary cells.

PMID- 26311627
TI  - Protection by beta-Hydroxybutyric acid against insulin glycation, lipid
      peroxidation and microglial cell apoptosis.
AB  - BACKGROUND: Diabetes mellitus is characterized jointly by hyperglycemia and
      hyperinsulinemia that make insulin more prone to be glycated and evolve insulin
      advanced glycation end products (Insulin- AGE). Here, we report the effect of
      beta-hydroxy butyrate (BHB) (the predominant ketone body) on the formation of
      insulin-AGE, insulin glycation derived liposomal lipid peroxidation and insulin
      AGE toxicity in microglial cells. METHODS: The inhibitory effect of BHB was
      monitored as a result of insulin incubation in the presence of glucose or
      fructose using AGE-dependent fluorescence, Tyr fluorescence as well as
      anilinonaphthalenesulfonate (ANS) andthioflavin T (ThT) binding, and circular
      dichroism (CD) investigations. To study lipid peroxidation induced by insulin
      glycation, thiobarbituric acid (TBA) assay and thiobarbituric acid reactive
      substance (TBARS) monitoring were used. The effect of insulin-AGE on microglial
      viability was investigated by 3-(4, 5 dimethylthiazol-2-yl)-2, 5
      diphenyltetrazoliumbromide (MTT) cell assay and Annexin V/propidium iodide (PI)
      staining. RESULTS: Here we are reporting the inhibitory effect of BHB on insulin
      glycation and generation of insulin-AGE as a possible explanation for insulin
      resistance. Moreover, the protective effect of BHB on consequential glycation
      derived liposomal lipid peroxidation as a causative event in microglial apoptosis
      is reported. CONCLUSION: The reduced insulin fibril formation, structural inertia
      to glycation involved conformational changes, anti-lipid peroxidation effect, and
      increasing microglia viability indicated the protective effect of BHB that
      disclose insight on the possible preventive effect of BHB on Alzheimer's disease.

PMID- 26311625
TI  - Retinoid-xenobiotic interactions: the Ying and the Yang.
AB  - The literature provides compelling evidence pointing to tight metabolic
      interactions between retinoids and xenobiotics. These are extensive and important
      for understanding xenobiotic actions in the body. Within the body, retinoids
      affect xenobiotic metabolism and actions and conversely, xenobiotics affect
      retinoid metabolism and actions. This article summarizes data that establish the
      importance of retinoid-dependent metabolic pathways for sustaining the body's
      responses to xenobiotic exposure, including the roles of all-trans- and 9-cis
      retinoic acid for protecting mammals from harmful xenobiotic effects and for
      ensuring xenobiotic elimination from the body. This review will also consider
      molecular mechanisms underlying xenobiotic toxicity focusing on how this may
      contribute to retinoid deficiency and disruption of normal retinoid homeostasis.
      Special attention is paid to xenobiotic molecular targets (nuclear receptors,
      regulatory proteins, enzymes, and transporters) which affect retinoid metabolism
      and signaling. 

PMID- 26311628
TI  - Acute Stroke or Transient Ischemic Attack Treated with Aspirin or Ticagrelor and
      Patient Outcomes (SOCRATES) trial: rationale and design.
AB  - RATIONALE: The risk of recurrent ischemia is high in the acute period after
      ischemic stroke and transient ischemic attack. Aspirin is recommended by
      guidelines for this indication, but more intensive antiplatelet therapy may be
      justified. AIMS: We aim to evaluate whether ticagrelor, a potent antiplatelet
      agent that blocks the P2Y12 receptor without requiring metabolic activation,
      reduces the risk of major vascular events compared with aspirin when
      randomization occurs within 24 h after symptom onset of a nonsevere ischemic
      stroke or high-risk transient ischemic attack. DESIGN: Acute Stroke or Transient
      Ischemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes
      (SOCRATES) is a randomized, double-blind, event-driven trial and will include an
      estimated 13,600 participants randomized in 33 countries worldwide to collect 844
      primary events. STUDY OUTCOMES: The primary endpoint is the composite of stroke
      (ischemic or hemorrhagic), myocardial infarction, and death. Time to the first
      primary endpoint will be compared in the treatment groups during 90-day follow
      up, with major hemorrhage serving as the primary safety endpoint. Participants
      will be followed for an additional 30 days after the randomized treatment period.
      DISCUSSION: The SOCRATES trial fulfills an important clinical need by evaluating
      a potent antiplatelet agent as a superior alternative to current standard of care
      in patients presenting acutely with ischemic stroke or transient ischemic attack.

PMID- 26311629
TI  - Preliminary clinical investigation of cataract surgery with a noncontact
      femtosecond laser system.
AB  - BACKGROUND AND OBJECTIVE: Femtosecond laser-assisted cataract surgery (FLACS) is
      rapidly gaining popularity due to the improved consistency and predictability for
      capsulorhexis. This study aimed to investigate the preliminary clinical outcomes
      of FLACS with a noncontact femtosecond laser system. PATIENTS AND METHODS: This
      prospective study enrolled 25 eyes in the trial group underwent FLACS (LLS-fs 3D,
      LENSAR, USA), and 29 eyes in the control group underwent conventional cataract
      surgery (Stellaris, Bausch & Lomb, USA). The phacoemulsification time, energy,
      and complications during operation were recorded. Postoperative refraction at 1
      day, 1 week, 1 and 3 months, the capsulorhexis size and corneal endothelial
      density at 1 and 3 months were also measured. RESULTS: Compared to the control
      group, reduction in phacoemulsification time was 51.5% (P = 0.02), and in overall
      energy, 65.1% (P = 0.02) in the trial group. In the trial group and the control
      group, total time of cataract procedure was 10.04 +/- 1.37 minutes, 10.52 +/-
      1.92 minutes, respectively (P = 0.31); the absolute difference between attempted
      and achieved capsulorhexis diameter at 1 month was 192.9 +/- 212.0 um, 626.9 +/-
      656.6 um, respectively (P = 0.04), and at 3 months, 256.6 +/- 181.9 um, 572.1 +/-
      337.0 um, respectively (P= 0.03); the absolute difference between attempted and
      achieved spherical equivalent at 3 months was 0.16 +/- 0.16 D, 0.74 +/- 0.65 D,
      respectively (P < 0.01); mean corneal endothelial cell loss at 1 month was 15.6%
      and 14.2%, respectively (P = 0.77), and at 3 months, 2.9%, 4.2%, respectively (P
      = 0.50). CONCLUSIONS: With the noncontact femtosecond laser system, FLACS can
      significantly improve the accuracy and repeatability of capsulorhexis, reduce the
      phacoemulsification time and overall energy, and enhance the predictability and
      stability of postoperative refraction.

PMID- 26311630
TI  - Luminescence study of Eu(3+) doped Li6 Y(BO3 )3 phosphor for solid-state
      lighting.
AB  - In this study, Li6 Y1-x Eux (BO3 )3 phosphor was successfully synthesized using a
      modified solid-state diffusion method. The Eu(3+) ion concentration was varied at
      0.05, 0.1, 0.2, 0.5 and 1 mol%. The phosphor was characterized for phase purity,
      morphology, luminescent properties and molecular transmission at room
      temperature. The XRD pattern suggests a result closely matching the standard
      JCPDS file (#80-0843). The emission and excitation spectra were followed to
      discover the luminescence traits. The excitation spectra indicate that the
      current phosphor can be efficiently excited at 395 nm and at 466 nm (blue light)
      to give emission at 595 and 614 nm due to the (5) D0  -> (7) Fj transition of
      Eu(3+) ions. Concentration quenching was observed at 0.5 mol% Eu(3+) in the Li6
      Y1-x Eux (BO3 )3 host lattice. Strong red emission with CIE chromaticity
      coordinates of phosphor is x = 0.63 and y = 0.36 achieved with dominant red
      emission at 614 nm the (5) D0  -> (7)  F2 electric dipole transition of Eu(3+)
      ions. The novel Li6 Y1-x Eux (BO3 )3 phosphor may be a suitable red-emitting
      component for solid-state lighting using double-excited wavelengths, i.e. near-UV
      at 395 nm and blue light at 466 nm. Copyright (c) 2015 John Wiley & Sons, Ltd. 

PMID- 26311631
TI  - An efficient system for intracellular delivery of beta-lactam antibiotics to
      overcome bacterial resistance.
AB  - The "Golden era" of antibiotics is definitely an old story and this is especially
      true for intracellular bacterial infections. The poor intracellular
      bioavailability of antibiotics reduces the efficency of many treatments and
      thereby promotes resistances. Therefore, the development of nanodevices coupled
      with antibiotics that are capable of targeting and releasing the drug into the
      infected-cells appears to be a promising solution to circumvent these
      complications. Here, we took advantage of two natural terpenes (farnesyl and
      geranyl) to design nanodevices for an efficient intracellular delivery of
      penicillin G. The covalent linkage between the terpene moieties and the
      antibiotic leads to formation of prodrugs that self-assemble to form
      nanoparticles with a high drug payload between 55-63%. Futhermore, the addition
      of an environmentally-sensitive bond between the antibiotic and the terpene led
      to an efficient antibacterial activity against the intracellular pathogen
      Staphylococcus aureus with reduced intracellular replication of about 99.9%
      compared to untreated infected cells. Using HPLC analysis, we demonstrated and
      quantified the intracellular release of PenG when this sensitive-bond (SB) was
      present on the prodrug, showing the success of this technology to deliver
      antibiotics directly into cells. 

PMID- 26311632
TI  - A Hollow Foldecture with Truncated Trigonal Bipyramid Shape from the Self
      Assembly of an 11-Helical Foldamer.
AB  - The creation of self-assembling microscale architectures that possess new and
      useful physical properties remains a significant challenge. Herein we report that
      an 11-helical foldamer self-assembles in a controlled manner to form a series of
      3D foldectures with unusual three-fold symmetrical shapes that are distinct from
      those generated from 12-helical foldamers. The foldamer packing motif was
      revealed by powder X-ray diffraction technique, and provides an important link
      between the molecular-level symmetry and the microscale morphologies. The utility
      of foldectures with hollow interiors as robust and well-defined supramolecular
      hosts was demonstrated for inorganic, organic, and even protein guests. This work
      will pave the way for the design of functional foldectures with greater 3D shape
      diversity and for the development of biocompatible delivery vehicles and
      containment vessels. 

PMID- 26311634
TI  - Latent variable modeling and its implications for institutional review board
      review: variables that delay the reviewing process.
AB  - BACKGROUND: To investigate the factors related to approval after review by an
      Institutional Review Board (IRB), the structure equation model was used to
      analyze the latent variables 'investigators', 'vulnerability' and 'review
      process' for 221 proposals submitted to our IRB. METHODS: The vulnerability
      factor included vulnerable cases, and studies that involved drug tests and
      genetic analyses. The principal investigator (PI) factor included the license
      level of the PI and whether they belonged to our institution. The review factor
      included administration time, total review time, and revision frequency. The
      revision frequency and total review time influenced the efficiency of review.
      RESULTS: The latent variable of reviewing was the most important factor mediating
      the PIs and vulnerability to IRB review approval. The local PIs moderated with
      genetic study and revision frequency had an impact on the review process and
      mediated non-approval. CONCLUSIONS: Better guidance of the investigators and
      reviewers might improve the efficiency with which IRBs function.

PMID- 26311635
TI  - [Guidelines for diagnosis and treatment of intrahepatic cholestasis of pregnancy
      (2015)].

PMID- 26311636
TI  - [Review and further explain the new "guidelines for diagnosis and treatment of
      intrahepatic cholestasis of pregnancy (2015)"].

PMID- 26311637
TI  - [Carrying out programming strategies for postpartum family planning, the new
      challenge to maternal and child health care service in China].

PMID- 26311638
TI  - [Correlation of the expressions of advanced glycation end products and its
      receptor in serum and placenta with the pathogenesis of preeclampsia].
AB  - OBJECTIVE: To investigate the correlation of the expressions of advanced
      glycation end products (AGE) and the receptor for advanced glycation end products
      (RAGE) in serum and placenta with the pathogenesis of preeclampsia. METHODS: From
      December 2013 to June 2014, 32 women with severe preeclampsia who received
      cesarean section in the Affiliated Hospital of Qingdao University were recruited
      in the study, defined as the severe preeclampsia group. 30 healthy pregnant women
      who received cesarean section in the same hospital were recruited as the control
      group. ELISA was used to measure the maternal serum AGE, soluble receptor for
      advanced glycation end products (sRAGE) and tumor necrosis factor-alpha (TNF
      alpha) in these women. Furthermore, ELISA was also used to measure AGE and TNF
      alpha in the placenta. The localizations of AGE and RAGE protein in placentas
      were detected by immunohistochemical SP method. RAGE and TNF-alpha mRNA
      expression in placentas were measured by real-time quantitative PCR. AGE, RAGE
      and TNF-alpha protein expression in placentas were measured by western blot,
      respectively. RESULTS: (1) The serum levels of AGE, sRAGE and TNF-alpha in the
      severe preeclampsia group were (538 +/- 75), (367 +/- 86) and (322 +/- 40) ng/L,
      respectively. They were significantly higher than those in the control group
      [(454 +/- 50), (286 +/- 35) and (270 +/- 35) ng/L, respectively] (P < 0.05). The
      levels of AGE showed positive correlation with the levels of TNF-alpha (r =
      0.588, P < 0.05), while the levels of sRAGE showed no correlation with TNF-alpha
      (r = -0.041, P > 0.05). (2) In the severe preeclampsia group, the levels of AGE
      and TNF-alpha in placentas were (500 +/- 82) and (334 +/- 57) ng/L, which were
      higher than those in the control group [(431 +/- 74) and (263 +/- 46) ng/L,
      respectively] (P < 0.05). The levels of AGE showed positive correlation with the
      levels of TNF-alpha (r = 0.406, P < 0.05). (3) AGE and RAGE protein mainly
      located in the syncytiotrophoblasts, macrophages and vascular endothelial cells
      in the placentas of the two groups. AGE expressed mainly in the cytoplasm, and
      RAGE expressed in the cytoplasm and cell membranes. (4) RAGE and TNF-alpha mRNA
      expression in the placentas of the severe preeclampsia group were 12.6 +/- 4.6
      and 10.4 +/- 2.4, which were significantly higher than those in the control group
      (0.9 +/- 0.4 and 3.5 +/- 0.9, P < 0.01). (5) The expressions of AGE, RAGE and TNF
      alpha protein in placentas of the severe preeclampsia group were 0.68 +/- 0.06,
      0.82 +/- 0.08 and 0.76 +/- 0.08. All were significantly higher than those of the
      control group (0.46 +/- 0.05, 0.42 +/- 0.09 and 0.52 +/- 0.07; P < 0.01).
      CONCLUSIONS: The levels of AGE and RAGE in serum and placentas elevated in the
      severe preeclampsia group, and the expression of TNF-alpha also elevated. These
      indicated that AGE and RAGE might be involved in the systemic inflammatory
      response and local inflammatory response in placentas, and then caused the
      preeclampsia.

PMID- 26311639
TI  - [Clinical research of transvaginal repair of cesarean scar diverticulum].
AB  - OBJECTIVE: To explore the clinical effect of transvaginal repair of cesarean scar
      diverticulum (CSD). METHODS: Totally 64 patients of CSD in the First Maternity
      and Infant Hospital, Tongji University between Mar. 2013 and Sept. 2014 underwent
      transvaginal repair of CSD were reviewed retrospectively and followed. RESULT:
      All the patients had a prolonged period, and the duration was (14.8 +/- 3.5)
      days; all the patients were received the transvaginal repair of CSD, there was no
      intra-operative complications, the procedures were successfully performed in all
      patients. The mean operation time was (67 +/- 12) minutes, the mean blood loss
      was (53 +/- 32) ml, and the mean length of hospital stay was (4.0 +/- 1.1) days.
      All patients were followed after the operation, the duration of menstruation was
      (8.1 +/- 3.5) days shorter in average, which was statistically significant (P <
      0.01); the operation effective rate was 94% (60/64) to assess the clinic syptoms,
      the operation effective rate was 95% (61/64) for anatomic assessment. The
      distance of the CSD from the serosa became thicker after surgery significantly,
      the distance was thicker (3.4 +/- 0.4) mm compared with preoperation (P < 0.01).
      CONCLUSIONS: Transvaginal repair of CSD offers minimal invasiveness, good
      exposure and accurate resection. It is worth to be popularized in the treatment
      of patients with CSD.

PMID- 26311640
TI  - [Efficacy and safety of mifepristone combined with misoprostol for termination of
      pregnancy between 8 and 16 weeks of gestation].
AB  - OBJECTIVE: To assess the efficacy and safety of mifepristone combined with oral
      or vaginal misoprostol for termination of pregnancy between 8 and 16 weeks of
      gestation. METHODS: This was a randomized, multi-center, open clinical trial. A
      total of 625 women at 8-16 weeks of gestation were randomized to receive 200 mg
      oral mifepristone followed by either oral misoprostol 400 ug every 3 hours or
      vaginal misoprostol 400 ug every 6 hours for a maximum of 4 doses 36-48 hours
      later. There were 417 women in oral group with 198 at 8-9 weeks and 219 at 10-16
      weeks, while 208 women in vaginal group with 99 at 8-9 weeks and 109 at 10-16
      weeks. The outcome measures were the success abortion rate, induction to abortion
      interval, the amount of bleeding, reoccurrence of menstruation and adverse
      events. RESULTS: Abortion rate was significantly higher in vaginal group [98.1%
      (202/206)] than that in oral group [94.0% (390/415), P = 0.023]; concerning
      termination of pregnancy at 8-9 weeks and 10-16 weeks respectively, there were no
      significant differences between oral and vaginal groups (P = 0.156, P = 0.073).
      The induction to abortion interval was no significant difference in oral and
      vaginal group in different gestational weeks (P = 0.238, P = 0.273). The average
      induction to abortion interval was (4.1 +/- 6.6) hours and (6.0 +/- 4.5) hours
      respectively in terminating 8-9 weeks and 10-16 weeks of gestation. Concerning
      the amount of bleeding within 2 hours of placenta expulsion, there was
      significant difference between oral group [(63 +/- 46) ml] and vaginal group [(55
      +/- 45) ml] in terminating 8-9 weeks of gestation (P = 0.047), while there was no
      significant difference between groups in terminating 10-16 weeks of gestation
      [oral group (76 +/- 52) ml versus vaginal group (76 +/- 61) ml, P = 0.507]. The
      reoccurrence of menstruation was about 37 days in both oral and vaginal groups.
      Two cases of incomplete abortion were serious adverse events (SAE) relating to
      treatment. The common adverse events (AE) of nausea and vomiting were
      significantly higher in oral group [57.2% (239/417), 36.3% (151/417)] than those
      in vaginal group [45.4% (94/208), 26.1% (54/208); P = 0.005, 0.011]. CONCLUSION:
      Oral or vaginal misoprostol combined with mifepristone, is effective and safe for
      termination of pregnancy between 8 and 16 weeks of gestation.

PMID- 26311641
TI  - [Mechanism of 17beta-estrogen on intracellular free calcium regulation in smooth
      muscle cells at the endometrial-myometrial interface in uteri with adenomyosis].
AB  - OBJECTIVE: To investigate the regulation mechanism of estrogen on the free
      calcium of smooth muscle cells at the endometrial-myometrial interface (EMI) in
      uteri with adenomyosis. METHODS: From September 2011 to November 2012, 59 uterine
      myometrial specimens were obtained from 59 cases underwent hysterectomy,
      including 28 adenomyosis patients as adenomyosis (ADS) group and 31 patients with
      cervical intraepithelial neoplasia III as control group. EMI smooth muscle cells
      were cultured and loaded with calcium ion fluorescent probe fluo-4/AM. After
      treated with trisphosphate (IP3) receptor antagonist, blocker of sarcoplasmic
      reticulum calcium-adenosine triphosphate (ATP), depleted agent of the ryanodine
      receptor-operated Ca(2+), inhibitor of L-type calcium channel, inhibitor of Na(+)
      Ca(2+) exchanger, the labeled cells were stimulated with estrogen. The changes of
      intracellular Ca(2+) fluorescence intensity were detected by laser scanning
      microscopy. The changes of intracellular Ca(2+) concentration was indicated by
      ?F[Ca(2+)](i). RESULTS: (1) Under normal calcium conditions, after the
      stimulation of estrogen, intracellular Ca(2+) fluorescence intensity in ADS group
      and control group both increased than those without estrogen. The ?F[Ca(2+)](i)
      in ADS group was 384 +/- 26, and in the control group ?F[Ca(2+)](i) was 235 +/-
      20. The ?F[Ca(2+)](i) in ADS group was higher than that in the control (P <
      0.01). Without calcium conditions, the ?F[Ca(2+)](i) in ADS group was 207 +/- 17,
      and in the control group ?F[Ca(2+)](i) was 221 +/- 19. The ?F[Ca(2+)](i) in ADS
      group was almost the same with the increase in the control (P = 0.731). The
      ?F[Ca(2+)](i) in ADS group was significantly decreased compared with the calcium
      condition (P < 0.01). However, there was no significant difference in the control
      between with and without calcium conditions (P = 0.060). (2) After treated with
      IP3 receptor antagonist, blocker of sarcoplasmic reticulum calcium-ATP, depleted
      agent of the ryanodine receptor-operated Ca(2+), the ?F[Ca(2+)]i in both groups
      were significantly reduced (P < 0.05), the increase in ADS group was
      significantly higher than that in the control (P < 0.05). (3)After treated with
      inhibitor of L-type calcium channel, the ?F[Ca(2+)](i) in ADS group was 211 +/-
      19, while in the control group ?F[Ca(2+)](i) was 203 +/- 16, and there was no
      significantly increased intracellular Ca(2+) in both groups (P > 0.05). But, the
      ?F[Ca(2+)](i) in ADS group was significantly reduced after treatment compared to
      before treatment, (211 +/- 19 vs 384 +/- 28; P = 0.001). The increase in control
      group was almost the same with before (203 +/- 16 vs 234 +/- 22, P = 0.141). (4)
      After treated with inhibitor of Na(+)-Ca(2+) exchanger, the ?F[Ca(2+)](i) in ADS
      group was 357 +/- 24 and in the control ?F[Ca(2+)](i)was 209 +/- 19. The increase
      in ADS group was significant higher than that in the control (P = 0.000).
      Compared with ?F[Ca(2+)](i) on the condition without treating with inhibitor of
      Na(+)-Ca(2+) exchanger, ?F[Ca(2+)](i) was 363 +/- 21 in ADS group and
      ?F[Ca(2+)](i) was 237 +/- 20 in control group after treatment. When compared with
      before treatment, there was no significant difference in both groups (P > 0.05).
      CONCLUSIONS: The increase of intracellular Ca(2+) induced by estrogen at EMI
      smooth muscle cells in adenomyosis patients was mostly from the release of
      arcoplasmic reticulum, and also from the Ca(2+) influx controlled by L-type
      calcium channel. The increase of Ca(2+) inducing abnormal contraction of EMI
      muscle may have relationship with the development of adenomyosis.

PMID- 26311642
TI  - [Clinical analysis of patients underwent hysterectomy for stage I cervical cancer
      or high grade cervical intraepithelial neoplasia with vaginal intraepithelial
      neoplasia].
AB  - OBJECTIVE: To analyse the necessity of colposcopic directed biopsy to vaginal
      intraepithelial neoplasia (VAIN) before hysterectomy due to early stage cervical
      cancer (stage I) or high grade cervical intraepithelial neoplasia (CIN). METHODS:
      A total of 669 patients who underwent a hysterectomy due to early stage cervical
      cancer (stage I) and CIN III in Beijing Obstetrics and Gynecology Hospital,
      Capital Medical University, from January 1, 2009 to December 31, 2013 and
      followed up, 99 patients with VAIN were enrolled. The clinical data and following
      up the prognosis were prospectively analyzed retrospectively. RESULTS: The
      occurrence rate of VAIN before and after hysterectomy due to cervical dysplasia
      was 14.8% (99/669), the occurrence rate and the grade of VAIN showed that
      significantly increased from CIN III to cervical cancer stage I (P < 0.05); Only
      15 patients enrolled had undergone vaginal wall biopsy by colposcopy pre
      hysterectomy, including 11 patients who were diagnosed with VAIN II-III and
      underwent vagina extended resection during the hysterectomy. The 5 year
      recurrence rate of vaginal stump VAIN after hysterectomy was 12.1% (12/99) and
      the progression rate was 4.0% (4/99), the recurrent rate was 2.0% (2/99).
      CONCLUSIONS: For all the patients who are planning to undergo hysterectomy due to
      stage I cervical cancer and CIN III, routine upper side of the vagina wall
      colposcopic-directed biopsy prehysterectomy is strongly recommended. All the
      patients after hysterectomy due to cervical dysplasia should be followed up
      regularly within 3 years after hysterectomy.

PMID- 26311643
TI  - [Protective effect of estrogen on acute lung injury after hemorrhagic shock in
      pregnant rabbit].
AB  - OBJECTIVE: The paper is an attentative effort to evaluate the reaction and
      mechanism of estrogen on pregnant rabbits with acute lung injury caused by
      hemorrhagic shock. METHODS: Sixty pregnant New Zealand white rabbits were
      randomly divided into 6 groups, with 10 rabbits in each group, namely normal
      control group (NG group, with anesthesia only), estrogen group (E(2)G group, with
      additional estrogen injection at 60 min) and the other four hemorrhagic shock
      groups underwent hemorrhagic shock (i.e. E(2)SG, FSG, SBSG, E(2)SBSG group; mean
      blood pressure- 40 mmHg (1 mmHg = 0.133 kPa) by phlebotomy for 15 min. After
      maintenance of the pressure for 45 min, the rabbits were treated with E(2) (0.37
      mg/kg), fructose injection (5%, 2 ml/kg), the p38 mitogen-activated protein
      kinases (p38MAPK) inhibitor SB-203580 (2 mg/kg) or E(2) plus SB-203580. Tumor
      necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6) were measured at
      different time points (0 min, 60 min, 80 min and 260 min), lung tissue methane
      dicarboxylic aldehyde (MDA) level, lung tissue myeloperoxidase (MOP), superoxide
      dismutase (SOD) activity, lung tissue dry weight/wet weight (DW/WW) value were
      measured after the experiment was finished, pulmonary pathology of the rabbits
      was observed. RESULT: (1) Serum TNF-alpha level of NG group and E(2)SG group were
      not significantly different compared with the other four groups at the 0 min and
      60 min. At 80 min and 260 min of experiment, serum TNF-alpha level of all the
      four shock groups were increased, E(2)SG group [(172.4 +/- 16.0) and (216.7 +/-
      18.6) ng/L], FSG group [(171.6 +/- 9.1) and (263.9 +/- 7.8) ng/L], SBSG group
      [(172.8 +/- 7.2) and (300.6 +/- 4.8) ng/L], E(2)SBSG group [(167.9 +/- 4.8 ) and
      (261.8 +/- 9.6) ng/L], and significantly higher than NG group and E(2)G group,
      separately (P < 0.05). (2) Serum IL-6 level of NG group and E(2)SG group were not
      significantly different compared with the other four groups at the 0 min, 60 min
      and 80 min. At 260 min, the serum IL-6 level [(98.3 +/- 0.9) and (110.4 +/- 1.8)
      ng/L; (120.9 +/- 2.3) and (109.8 +/- 2.6) ng/L] of the four shock groups (E(2)SG,
      FSG, SBSG, E(2)SBSG group) were significantly higher than NG group and E(2)G
      group (P < 0.05). (3) Lung tissue MDA level [(2.20 +/- 0.12), (2.57 +/- 0.11),
      (3.17 +/- 0.08), (2.75 +/- 1.09) nmol/mg] and MPO activity [(4.45 +/- 0.25),
      (6.65 +/- 0.56), (9.55 +/- 0.30), (6.78 +/- 0.11) U/mg] of the four shock groups
      (E(2)SG, FSG, SBSG, E(2)SBSG group) were higher than NG group and E(2)G group (P
      < 0.05). (4) Lung tissue SOD activity [(51.8 +/- 1.8), (40.2 +/- 1.5), (30.0 +/-
      1.7), (41.2 +/- 2.0) U/mg] was significantly higher in the four shock groups
      (E(2)SG, FSG, SBSG, E(2)SBSG group) compared with NG group and E(2)G group (P <
      0.05). (5) Lung tissue DW/WW value (0.143 +/- 0.008, 0.127 +/- 0.008, 0.109 +/-
      0.006, 0.125 +/- 0.008) was significantly lower in the four shock groups (E(2)SG,
      FSG, SBSG, E(2)SBSG group) compared with NG group and E(2)G group (P < 0.05). (6)
      Lung tissue of the rabbits in NG group and E(2)G group is basically normal
      without obvious pathology changes. Lung tissue pathological damage of rabbits was
      observed in the four shock groups, and the pathological damage of rabbits in SBSG
      group was most serious. CONCLUSION: Estrogen can reduce acute lung injury of
      pregnant rabbits with hemorrhagic shock, the p38MAPK pathway plays a critical
      role in mediating the salutary effects of E(2) on shock-induced acute lung
      injury.

PMID- 26311644
TI  - [Effect of 1,3-O,N spiroheterocyclic inhibitors of heparanase on the growth of
      HeLa cells].
AB  - OBJECTIVE: To provide the theoretical supportting for targeted heparanase (HPA)
      inhibition of cervical cancer through observing the anti-proliferative effect of
      the HPA inhibitor on HeLa cell line of cervical cancer. METHODS: The two series
      of 13 kinds of novel HPA inhibitors were synthesized and optimized. Heparan
      degrading enzyme assay kit was used to test the effect of the inhibitors on the
      inhibition of HPA enzyme activity. Methyl thiazolyl tetrazolium (MTT) method and
      scratch test were used to observe the anti-proliferative and the migration effect
      of the inhibitors on HeLa cells. Flow cytometry was performed to determine the
      cell cycles and apoptosis. The expression of HPA was evaluated by reverse
      transcription (RT)-PCR, western blot and immunocytochemistry. RESULTS: All tested
      inhibitors could inhibit the activity of HPA enzyme [the range of 50% inhibiting
      concentration (IC50) values from 4.47 to 47.19 umol/L] and the growth of HeLa
      cells (the range of IC50 values from 48.16 to 96.64 umol/L). Among them, No.16
      compound exhibits the strongest inhibition against the growth of HeLa, which
      could arrest the cell into G0/G1 and G2/M phases. The rate of cell apoptosis in
      the group treated with 50 umol/L No.16 for 48 hours [(11.9 +/- 1.2)%] was
      significantly higher than that [(6.6 +/- 1.8)%] in untreated group (P = 0.013).
      Real time PCR and western blot showed that expression levels of HPA mRNA (1.23 +/
      0.46) and protein (0.46 +/- 0.31) significantly decreased in the treated group
      as compared with the levels of HPA mRNA (3.43 +/- 0.45) and protein (1.30 +/-
      0.58) in the untreated group (both P < 0.05). Immunocytochemistry also showed
      that the treatment of No.16 significantly reduced the average optical density
      (0.39 +/- 0.04) of HPA immuostaining signal compared with that in the control
      group (0.50 +/- 0.09; P = 0.026). CONCLUSION: Novel 1,3-O,N spiroheterocyclic HPA
      inhibitors could inhibit the proliferation of HeLa cells, inhibit the HPA enzyme
      activity in different degree, and downregulate the expression of HPA protein.

PMID- 26311645
TI  - The unified ICE-CBF pathway provides a transcriptional feedback control of
      freezing tolerance during cold acclimation in Arabidopsis.
AB  - During cold acclimation, C-repeat binding factors (CBFs) activate downstream
      targets, such as cold-regulated genes, leading to the acquisition of freezing
      tolerance in plants. Inducer of CBF expression 1 (ICE1) plays a key role by
      activating CBF3 expression in shaping the cold-induced transcriptome. While the
      ICE1-CBF3 regulon constitutes a major cold acclimation pathway, gene regulatory
      networks governing the CBF signaling are poorly understood. Here, we demonstrated
      that ICE1 and its paralog ICE2 induce CBF1, CBF2, and CBF3 by binding to the gene
      promoters. ICE2, like ICE1, was ubiquitinated by the high expression of
      osmotically responsive gene 1 (HOS1) E3 ubiquitin ligase. Whereas ICE2-defective
      ice2-2 mutant did not exhibit any discernible freezing-sensitive phenotypes, ice1
      2 ice2-2/+ plant, which is defective in ICE1 and has a heterozygotic ice2
      mutation, exhibited significantly reduced freezing tolerance. Accordingly, all
      three CBF genes were markedly down-regulated in the ice1-2 ice2-2/+ plant,
      indicating that ICE1 and ICE2 are functionally redundant with different
      implementations in inducing CBF genes. Together with the negative regulation of
      CBF3 by CBF2, we propose that the unified ICE-CBF pathway provides a
      transcriptional feedback of freezing tolerance to sustain plant development and
      survival during cold acclimation.

PMID- 26311646
TI  - BDNF promotes the growth of human neurons through crosstalk with the Wnt/beta
      catenin signaling pathway via GSK-3beta.
AB  - Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal
      growth; however, the downstream regulatory mechanisms remain unclear. In this
      study, we investigated whether BDNF exerts its neurotrophic effects through the
      Wnt/beta-catenin signaling pathway in human embryonic spinal cord neurons in
      vitro. We found that neuronal growth (soma size and average neurite length) was
      increased by transfection with a BDNF overexpression plasmid. Western blotting
      and real-time quantitative PCR showed that expression of the BDNF pathway
      components TrkB, PI3K, Akt and PLC-gamma was increased by BDNF overexpression.
      Furthermore, the Wnt signaling factors Wnt, Frizzled and Dsh and the downstream
      target beta-catenin were upregulated, whereas GSK-3beta was downregulated. In
      contrast, when BDNF signaling was downregulated with BDNF siRNA, the growth of
      neurons was decreased. Furthermore, BDNF signaling factors, Wnt pathway
      components and beta-catenin were all downregulated, whereas GSK-3beta was
      upregulated. This suggests that BDNF affects the growth of neurons in vitro
      through crosstalk with Wnt signaling, and that GSK-3beta may be a critical factor
      linking these two pathways. To evaluate this possibility, we treated neurons with
      6-bromoindirubin-3'-oxime (BIO), a small molecule GSK-3beta inhibitor. BIO
      reduced the effects of BDNF upregulation/downregulation on soma size and average
      neurite length, and suppressed the impact of BDNF modulation on the Wnt signaling
      pathway. Taken together, our findings suggest that BDNF promotes the growth of
      neurons in vitro through crosstalk with the Wnt/beta-catenin signaling pathway,
      and that this interaction may be mediated by GSK-3beta. 

PMID- 26311647
TI  - NICE recommends tighter blood sugar control in diabetes to reduce risk of
      complications.

PMID- 26311648
TI  - Identification and Characterization of the Major Chemical Constituents in Fructus
      Akebiae by High-Performance Liquid Chromatography Coupled with Electrospray
      Ionization-Quadrupole-Time-of-Flight Mass Spectrometry.
AB  - Fructus Akebiae (FA), the dry fruit of Akebia quinata (THUNB.) DECNE., possesses
      potent antidepressant properties. Owing to the structural complexity, high
      polarity and thermal lability in plants, it is difficult and time-consuming to
      analyze the major chemical constituents by traditional strategies that involve
      extraction, isolation, purification and identification by chemical manipulations
      and spectroscopic methods. In this study, a high-performance liquid
      chromatography coupled with electrospray ionization-quadrupole-time-of-flight
      mass spectrometry (HPLC-ESI-Q-TOF-MS-MS) method was established for quickly
      identifying the chemical constituents in the extract of Fructus Akebiae. The main
      saponin components in the extract of Fructus Akebiae were detected with the HPLC
      ESI-Q-TOF-MS-MS in negative-ion mode. These components were further analyzed by
      MS(2) spectra, and compared with the corresponding reference substances and
      literature data. Nineteen saponins in the extract of Fructus Akebiae were well
      separated in one run. The new method is accurate and rapid. It can be used to
      identify the main chemical constituents in the extract of Fructus Akebiae and can
      be suitable for the quality control of Fructus Akebiae. 

PMID- 26311649
TI  - Views of general practitioners on providing contraceptive advice and long-acting
      reversible contraception at the 6-week postnatal visit: a qualitative study.
AB  - BACKGROUND: Increased uptake of long-acting reversible contraception (LARC)
      postpartum could prevent more unintended pregnancies and short inter-birth
      intervals. General practitioners (GPs) play a pivotal role in providing
      postpartum contraception at the 6-week postnatal visit. AIM: To explore how GPs
      view their role in delivering postpartum contraception at the 6-week visit and on
      providing LARC at this time. METHODS: In-depth, semi-structured interviews with a
      purposive sample of 13 GPs in Edinburgh and the surrounding region in Scotland.
      The interviews were audio recorded, transcribed and thematically analysed.
      RESULTS: All GPs confirmed that contraception was routinely discussed at the
      postpartum visit, although this was usually the last item covered. Most felt that
      while 6-weeks postpartum was adequate for most women to commence contraception,
      it was often too late for young mothers (aged under 20 years) or women from
      deprived areas. GPs provided prescriptions for oral contraception at this visit,
      but insertion of a contraceptive implant required a further appointment. For
      intrauterine contraception, women typically required two additional visits to the
      GP (for counselling and then insertion) or were referred to a local sexual health
      service. Some GPs saw their role as the main provider of postpartum
      contraception, whereas others felt they complemented the actions of midwives and
      health visitors. CONCLUSIONS: This study demonstrated that although contraception
      is discussed at a routine 6-week postpartum visit with a GP, there are delays for
      women wishing to commence LARC that create scope for unintended pregnancy.
      Strategies to facilitate access to LARC postpartum should be explored.

PMID- 26311650
TI  - Genes with Restricted Introgression in a Field Cricket (Gryllus firmus/Gryllus
      pennsylvanicus) Hybrid Zone Are Concentrated on the X Chromosome and a Single
      Autosome.
AB  - Characterizing the extent of genomic differentiation between recently diverged
      lineages provides an important context for understanding the early stages of
      speciation. When such lineages form discrete hybrid zones, patterns of
      differential introgression allow direct estimates of which genome regions are
      likely involved in speciation and local adaptation. Here we use a backcross
      experimental design to construct a genetic linkage map for the field crickets
      Gryllus firmus and Gryllus pennsylvanicus, which interact in a well-characterized
      hybrid zone in eastern North America. We demonstrate that loci with major allele
      frequency differences between allopatric populations are not randomly distributed
      across the genome. Instead, most are either X-linked or map to a few small
      autosomal regions. Furthermore, the subset of those highly differentiated markers
      that exhibit restricted introgression across the cricket hybrid zone are also
      concentrated on the X chromosome (39 of 50 loci) and in a single 7-cM region of
      one autosome. Although the accumulation on the sex chromosome of genes
      responsible for postzygotic barriers is a well-known phenomenon, less attention
      has been given to the genomic distribution of genes responsible for prezygotic
      barriers. We discuss the implications of our results for speciation, both in the
      context of the role of sex chromosomes and also with respect to the likely causes
      of heterogeneous genomic divergence. Although we do not yet have direct evidence
      for the accumulation of ecological, behavioral, or fertilization prezygotic
      barrier genes on the X chromosome, faster-X evolution could make these barriers
      more likely to be X-linked. 

PMID- 26311652
TI  - Study of the association between the donors and recipients angiotensin-converting
      enzyme insertion/deletion gene polymorphism and the acute renal allograft
      rejection.
AB  - BACKGROUND: Angiotensin converting enzyme (ACE) is involved in various
      pathophysiological conditions including renal function. ACE levels are under
      genetic control. OBJECTIVES: This study was designed to investigate the
      association between the donors and recipients ACE-I/D gene polymorphism and risk
      of acute rejection outcome in renal allograft recipients. PATIENTS AND METHODS:
      ACE-I/D polymorphism was determined in 200 donor-recipient pairs who had been
      referred to Afzalipour hospital in Kerman. ACE-I/D polymorphism was detected
      using polymerase chain reaction (PCR). Acute rejection (AR) during at least six
      months post-transplantation was defined as a 20% increase in creatinine level
      from the postoperative baseline in the absence of other causes of graft
      dysfunction which responded to antirejection therapy. RESULTS: The observed
      allele frequencies were II 9.8%, ID 35.6% and DD 44.4% in donors and II 9.8%, ID
      35.1% and DD 52.7% in recipients. There were no significant association between
      ACE genotypes and AR episodes (ORID=0.96 [0.18-5.00] and ORDD: 1.24 [0.25-6.07]
      for the donors) and (ORID: 0.29 [0.06-1.45] and ORDD: 0.75 [0.19-2.90] for the
      recipients). CONCLUSIONS: It seems that donor and recipient ACE-I/D genotype
      might not be a risk factor for acute renal allograft rejection. However, due to
      conflicting results from this and other studies, multicenter collaborative
      studies with more participants and concomitant evaluation of ACE polymorphism
      with other polymorphisms in renin-angiotensin system (RAS) are suggested to
      determine whether ACE genotypes are significant predictors of renal allograft
      rejection.

PMID- 26311651
TI  - High-Throughput Cloning of Temperature-Sensitive Caenorhabditis elegans Mutants
      with Adult Syncytial Germline Membrane Architecture Defects.
AB  - The adult Caenorhabditis elegans hermaphrodite gonad consists of two mirror
      symmetric U-shaped arms, with germline nuclei located peripherally in the distal
      regions of each arm. The nuclei are housed within membrane cubicles that are open
      to the center, forming a syncytium with a shared cytoplasmic core called the
      rachis. As the distal germline nuclei progress through meiotic prophase, they
      move proximally and eventually cellularize as their compartments grow in size.
      The development and maintenance of this complex and dynamic germline membrane
      architecture are relatively unexplored, and we have used a forward genetic screen
      to identify 20 temperature-sensitive mutations in 19 essential genes that cause
      defects in the germline membrane architecture. Using a combined genome-wide SNP
      mapping and whole genome sequencing strategy, we have identified the causal
      mutations in 10 of these mutants. Four of the genes we have identified are
      conserved, with orthologs known to be involved in membrane biology, and are
      required for proper development or maintenance of the adult germline membrane
      architecture. This work provides a starting point for further investigation of
      the mechanisms that control the dynamics of syncytial membrane architecture
      during adult oogenesis. 

PMID- 26311653
TI  - Tragacanth gum as a natural polymeric wall for producing antimicrobial
      nanocapsules loaded with plant extract.
AB  - Tragacanth gum as a biocompatible and biodegradable polymer with good properties
      including emulsifying, viscosity and cross-linking ability can be used as the
      wall material in encapsulation of different compounds, specifically plant
      extracts. In this paper, for the first time, Tragacanth gum was used to produce
      nanocapsules containing plant extract through microemulsion method. The effect of
      different parameters on the average size of prepared nanocapsules in presence of
      aluminum and calcium chloride through ultrasonic and magnetic stirrer was
      investigated. The high efficient nanocapsules were prepared with spherical shape
      and smooth surface. The average size of nanocapsules prepared through ultrasonic
      using aluminum chloride (22nm) was smaller than other products. The structure of
      prepared nanocapsules was studied by FT-IR spectroscopy. Antimicrobial activity
      of different nanocapsules against Escherichia coli, Staphylococcus aureus and
      Candida albicans was investigated by shake flask method during their release
      showed 100% microbial reduction after 12h stirring. 

PMID- 26311654
TI  - Evaluation of telehealth service for patients with congestive heart failure in
      the north of Israel.
AB  - AIMS: This research was conducted to evaluate the impact of a telehealth service
      on re-hospitalization of patients with congestive heart failure at New York Heart
      Association II-IV. METHODS AND RESULTS: The telehealth service for congestive
      heart failure patients was designed to follow the patients after their daily
      weighing and to provide a response in cases of non-compliance or deviation from
      baseline weight. A weighing scale was installed in the patient's house together
      with a communication module connected to the telemedicine control centre through
      a telephone line. The control centre is staffed by skilled nurses whose responses
      to patients are guided by programmed algorithm. Over a year, we evaluated the
      changes in the frequency of hospital admission and of primary care visits, and
      quality of life of 141 individuals who were eligible for the telehealth service
      for congestive heart failure. A decline was noted in the average number of
      hospitalizations per patient (from 4.7 to 2.6, p < 0.001). Scores of parameters
      of quality of life were improved (average score for first through fourth
      quarterly administration: 64, 50, 16, 16, p < 0.001 by the Minnesota Living with
      Heart Failure Questionnaire). CONCLUSIONS: During the year of use in telehealth
      service for congestive heart failure parameters of hospitalization were improved,
      together with parameters of quality of life.

PMID- 26311655
TI  - Burden and spectrum of infectious disease in Germany 2009-2014: a multicentre
      study from Berlin's Municipal Hospitals.
AB  - PURPOSE: This study aimed at assessing the burden and spectrum of infectious
      diseases (ID) in a Metropolitan population in Germany. METHODS: A discharge
      database using ICD-10 codes enabled the identification of hospitalizations with
      infection-related diagnoses. All hospital admissions between 2009 and 2014 were
      analysed from 9 municipal hospitals serving approximately one-third of an urban
      population of 3.5 million people. RESULTS: We identified 114,168 admissions with
      a primary (first-listed) ID diagnosis and 220,483 admissions with any-listed ID
      diagnosis, accounting for 8.9 % [95 % confidence interval (CI) 8.9-9.0 %] and
      17.2 % (95 % CI 17.1-17.3) of all 1,284,559 admissions, respectively. Annually,
      439,837 bed-days (range 413,707-488,520) were occupied by patients with an ID
      diagnosis, utilizing 22.8 % of total bed capacity. The median length of stay for
      patients with primary ID diagnosis and secondary ID diagnosis was 6 days (IQR 3
      11) and 10 days (IQR 5-19), respectively. The most common diagnosis across all
      age groups was "pneumonia" (22.8 and 16.2 % of ID admissions as primary and
      secondary diagnosis, respectively). In-hospital mortality was 6.8 % (95 % CI 6.6
      6.9) and 8.9 % (95 % CI 8.7-9.1) for ID as primary and secondary diagnosis,
      respectively. CONCLUSION: Infectious diseases contribute significantly to the
      overall burden of disease in a health system caring for an urban German
      population. In view of the magnitude of ID's contribution, establishing more
      specialists in ID medicine and adjusting the reimbursements for managing
      infection-related admissions should be made a public health priority in Germany.

PMID- 26311656
TI  - A high-throughput method for predicting drug effects on gut transit time using
      larval zebrafish.
AB  - INTRODUCTION: Zebrafish are an attractive vertebrate model due to their small
      size, transparency through organogenesis, and high fecundity. The zebrafish
      gastrointestinal (GI) tract is similar to the mammalian GI tract in gene
      expression, nervous system control, and response to chemical challenges. GI
      intolerance is a common preclinical finding and can be a serious clinical safety
      concern. Mammalian GI liability tests are conducted at the expense of time, test
      article, and labor. We developed a high-throughput method to predict mammalian GI
      safety issues using larval zebrafish. METHODS: Fluorescent food is fed to larval
      zebrafish (7 days post fertilization). After feeding, larvae are placed
      individually into wells of a 96-well plate and dosed with test compounds.
      Fluorescence is measured from the bottom of the wells repeatedly over the course
      of 24h and thus fecal accumulation is tracked over time. The area under the curve
      is compared between treated and vehicle-treated groups. RESULTS: Drugs with
      established clinical GI effects significantly impacted zebrafish GI transit time
      as measured by this method; tegaserod and metoclopramide accelerated transit
      time, while atropine and amitriptyline slowed transit time. This method is
      sensitive enough to reflect dose-level associated effects as demonstrated using
      atropine. Using a suite of 24 compounds with known (positive or negative)
      mammalian GI effects, we characterized this method as having a high positive
      predictive value. DISCUSSION: Here we present an efficient assay for predicting
      mammalian GI transit liabilities using larval zebrafish. With this assay, an
      investigator can evaluate dozens of compounds in a single day using very little
      amount of each test article. As such, safe drug candidates can be prioritized for
      mammalian testing, which expedites the discovery process and provides 3 Rs
      impact.

PMID- 26311657
TI  - Opponent's comments.

PMID- 26311658
TI  - Opponent's comments.

PMID- 26311660
TI  - Postprandial effects of consuming a staggered meal on gut peptide and glycemic
      responses in obese women and men.
AB  - Eating slowly by staggering a meal may reduce energy intake. Our aim was to
      examine the effect of eating a portion of beans 15min before the rest of the
      meal, on gastrointestinal (GI) peptides, glucose and insulin concentrations and
      subsequent energy intake in obese adults. This was a randomised crossover design
      study with 28 obese subjects. Participants consumed a standardised breakfast on
      test days followed by test meals: (1) control meal containing 86g (0.5 cup) of
      beans, and (2) staggered meal in which 86g (0.5 cup) of beans were consumed 15min
      before the rest of the meal. Blood obtained prior to and at 30, 60, and 120min
      following the meals was analysed for acylated ghrelin, unacylated ghrelin,
      glucagon-like peptide-1 (GLP-1), peptide YY, oxyntomodulin, glucose and insulin.
      Feelings of hunger and satiety were assessed using analog visual scales. Energy
      intake following the test meal was obtained by computer assisted dietary recalls.
      Mixed model statistical analysis of data showed time effects for unacylated
      ghrelin, GLP-1, glucose, insulin, hunger and fullness, however, meal effects were
      not shown for any of the parameters. GLP-1 area under the curve from baseline to
      120min (AUC0-120) decreased by 19% (P=0.024) and that of glucose increased by 7%
      (P=0.046) following the staggered compared to the control bean meal. Energy
      intake subsequent to the test meals did not differ between treatments. In
      conclusion, lengthening meal times by staggering eating did not benefit hormonal,
      metabolic or appetite control in obese individuals.

PMID- 26311661
TI  - The protective role of body appreciation against media-induced body
      dissatisfaction.
AB  - This study aimed to examine the protective role of positive body image against
      negative effects produced by viewing thin-idealised media. University women
      (N=68) completed trait measures of body appreciation and media protective
      strategies. At a subsequent session, participants viewed 11 thin-ideal
      advertisements. Body dissatisfaction was assessed before and after advertisement
      exposure, and state measures of self-objectification, appearance comparison, and
      media protective strategies were completed. Results indicated that body
      appreciation predicted less change in body dissatisfaction following exposure,
      such that participants with low body appreciation experienced increased body
      dissatisfaction, while those with high body appreciation did not. Although state
      appearance comparison predicted increased body dissatisfaction, neither state
      self-objectification nor appearance comparison accounted for body appreciation's
      protective effect. Trait and state media protective strategies positively
      correlated with body appreciation, but also did not account for body
      appreciation's protective effect. The results point to intervention targets and
      highlight future research directions. 

PMID- 26311662
TI  - Cationic micelle based vaccine induced potent humoral immune response through
      enhancing antigen uptake and formation of germinal center.
AB  - Nanoparticles have been proven to be an effective vaccine delivery system that
      can boost immune responses to subunit vaccines. Herein, we developed and
      characterized a cationic polymeric polyethylene glycol2000-poly epsilon
      caprolactone2000-polyethylenimine2000 (mPEG2000-PCL2000-g-PEI2000) micelle as a
      potent vaccine delivery system to boost the immune response in vivo. The micelles
      that we developed exhibited great antigen-loading capability and minimal
      cytotoxicity in vitro. Meanwhile, micelles facilitated OVA antigen uptake by
      dendritic cells both in vitro and in vivo. More importantly, a micelle-formulated
      OVA vaccine could significantly promote anti-OVA antibody production by 190-fold
      and potently enhance T cell proliferation and the secretion of IL-5 and IFN
      gamma. We attributed these effects to its ability to promote antigen uptake,
      antigen deposition, and germinal center formation. In conclusion, the mPEG2000
      PCL2000-PEI2000 micelle that we developed has potential as potent vaccine
      delivery system to induce Th2 immune response. 

PMID- 26311663
TI  - Competitors as accomplices: seaweed  competitors hide corals from predatory  sea
      stars.
AB  - Indirect biotic effects arising from multispecies interactions can alter the
      structure and function of ecological communities--often in surprising ways that
      can vary in direction and magnitude. On Pacific coral reefs, predation by the
      crown-of-thorns sea star, Acanthaster planci, is associated with broad-scale
      losses of coral cover and increases of macroalgal cover. Macroalgal blooms
      increase coral-macroalgal competition and can generate further coral decline.
      However, using a combination of manipulative field experiments and observations,
      we demonstrate that macroalgae, such as Sargassum polycystum, produce
      associational refuges for corals and dramatically reduce their consumption by
      Acanthaster. Thus, as Acanthaster densities increase, macroalgae can become coral
      mutualists, despite being competitors that significantly suppress coral growth.
      Field feeding experiments revealed that the protective effects of macroalgae were
      strong enough to cause Acanthaster to consume low-preference corals instead of
      high-preference corals surrounded by macroalgae. This highlights the context
      dependent nature of coral-algal interactions when consumers are common.
      Macroalgal creation of associational refuges from Acanthaster predation may have
      important implications for the structure,function and resilience of reef
      communities subject to an increasing number of biotic disturbances.

PMID- 26311664
TI  - Bacteriocin-mediated competition in cystic  fibrosis lung infections.
AB  - Bacteriocins are toxins produced by bacteria to kill competitors of the same
      species. Theory and laboratory experiments suggest that bacteriocin production
      and immunity play a key role in the competitive dynamics of bacterial strains.
      The extent to which this is the case in natural populations,especially human
      pathogens, remains to be tested. We examined the role of bacteriocins in
      competition using Pseudomonas aeruginosa strains infecting lungs of humans with
      cystic fibrosis (CF). We assessed the ability of different strains to kill each
      other using phenotypic assays, and sequenced their genomes to determine what
      bacteriocins (pyocins) they carry. We found that(i) isolates from later infection
      stages inhibited earlier infecting strains less,but were more inhibited by
      pyocins produced by earlier infecting strains and carried fewer pyocin types;
      (ii) this difference between early and late infections appears to be caused by a
      difference in pyocin diversity between competing genotypes and not by loss of
      pyocin genes within a lineage overtime; (iii) pyocin inhibition does not explain
      why certain strains outcompete others within lung infections; (iv) strains
      frequently carry the pyocin-killing gene, but not the immunity gene, suggesting
      resistance occurs via other unknown mechanisms. Our results show that, in
      contrast to patterns observed in experimental studies, pyocin production does not
      appear to have a major influence on strain competition during CF lung infections.

PMID- 26311665
TI  - The ecology of microscopic life in  household dust.
AB  - We spend the majority of our lives indoors; yet, we currently lack a
      comprehensive understanding of how the microbial communities found in homes vary
      across broad geographical regions and what factors are most important in shaping
      the types of microorganisms found inside homes. Here, we investigated the fungal
      and bacterial communities found in settled dust collected from inside and outside
      approximately 1200 homes located across the continental US, homes that represent
      a broad range of home designs and span many climatic zones. Indoor and outdoor
      dust samples harboured distinct microbial communities, but these differences were
      larger for bacteria than for fungi with most indoor fungi originating outside the
      home. Indoor fungal communities and the distribution of potential allergens
      varied predictably across climate and geographical regions; where you live
      determines what fungi live with you inside your home. By contrast, bacterial
      communities in indoor dust were more strongly influenced by the number and types
      of occupants living in the homes. In particular, the female : male ratio and
      whether a house had pets had a significant influence on the types of bacteria
      found inside our homes highlighting that who you live with determines what
      bacteria are found inside your home.

PMID- 26311666
TI  - Regressive evolution of the arthropod  tritocerebral segment linked to functional
      divergence of the Hox gene labial.
AB  - The intercalary segment is a limbless version of the tritocerebral segment and is
      present in the head of all insects, whereas other extant arthropods have retained
      limbs on their tritocerebral segment (e.g. the pedipalp limbs in spiders). The
      evolutionary origin of limb loss on the intercalary segment has puzzled
      zoologists for over a century. Here we show that an intercalary segment-like
      phenotype can be created in spiders by interfering with the function of the Hox
      gene labial. This links the origin of the intercalary segment to a functional
      change in labial. We show that in the spider Parasteatoda tepidariorum the labial
      gene has two functions: one function in head tissue maintenance that is conserved
      between spiders and insects, and a second function in pedipalp limb promotion and
      specification, which is only present in spiders. These results imply that labial
      was originally crucial for limb formation on the tritocerebral segment, but that
      it has lost this particular subfunction in the insect ancestor, resulting in limb
      loss on the intercalary segment. Such loss of a subfunction is away to avoid
      adverse pleiotropic effects normally associated with mutations in developmental
      genes, and may thus be a common mechanism to accelerate regressive evolution.

PMID- 26311667
TI  - Rapid eco-evolutionary responses in  perturbed phytoplankton communities.
AB  - Biodiversity currently faces unprecedented threats owing to species extinctions.
      Ecologically, compensatory dynamics can ensure stable community biomass following
      perturbation. However, whether there is a contribution of genetic diversity to
      community responses is an outstanding question. To date, the contribution of
      evolutionary processes through genotype shifts has not been assessed in naturally
      co-occurring multi-species communities in the field. We examined the mechanisms
      contributing to the response of a lake phytoplankton community exposed to either
      a press or pulse acidification perturbation in lake mesocosms. To assess
      community shifts in the ecological response of morphospecies, we identified taxa
      microscopically. We also assessed genotype shifts by sequencing the ITS2 region
      of ribosomal DNA. We observed ecological and genetic contributions to community
      responses. The ecological response was attributed to compensatory morphospecies
      dynamics and occurred primarily in the Pulse perturbation treatment. In the Press
      treatments, in addition to compensatory dynamics, we observed evidence for
      genotype selection in two species of chlorophytes, Desmodesmus cuneatus and an
      unidentified Chlamydomonas. Our study demonstrates that while genotype selection
      may be rare, it is detectable and occurs especially when new environmental
      conditions are maintained for long enough to force selection processes on
      standing variation.

PMID- 26311668
TI  - High effectiveness of tailored flower strips  in reducing pests and crop plant
      damage.
AB  - Providing key resources to animals may enhance both their biodiversity and the
      ecosystem services they provide. We examined the performance of annual flower
      strips targeted at the promotion of natural pest control in winter wheat. Flower
      strips were experimentally sown along 10 winter wheat fields across a gradient of
      landscape complexity (i.e. proportion non-crop area within 750 m around focal
      fields) and compared with 15 fields with wheat control strips. We found strong
      reductions in cereal leaf beetle(CLB) density (larvae: 40%; adults of the second
      generation: 53%) and plant damage caused by CLB (61%) in fields with flower
      strips compared with control fields. Natural enemies of CLB were strongly
      increased in flower strips and in part also in adjacent wheat fields. Flower
      strip effects on natural enemies, pests and crop damage were largely independent
      of landscape complexity(8-75% non-crop area). Our study demonstrates a high
      effectiveness of annual flower strips in promoting pest control, reducing CLB
      pest levels below the economic threshold. Hence, the studied flower strip offers
      a viable alternative to insecticides. This highlights the high potential of
      tailored agri-environment schemes to contribute to ecological intensification and
      may encourage more farmers to adopt such schemes.

PMID- 26311669
TI  - Self-discrimination in the tendrils  of the vine Cayratia japonica is mediated 
      by physiological connection.
AB  - Although self-discrimination has been well documented, especially in animals,
      self-discrimination in plants has been identified in only a few cases, such as
      self-incompatibility in flowers and root discrimination. Here, were port a new
      form of self-discrimination in plants: discrimination by vine tendrils. We found
      that tendrils of the perennial vine Cayratia japonica were more likely to coil
      around neighbouring non-self plants than neighbouring self plants in both
      experimental and natural settings. The higher level of coiling around a
      physiologically severed self plant compared with that around a physiologically
      connected self plant suggested that self-discrimination was mediated by
      physiological coordination between the tendril and the touched plant as reported
      for self-discrimination in roots. The results highlight the importance of self
      discrimination for plant competition not only underground,but also above-ground.

PMID- 26311670
TI  - Sickness behaviour associated with  non-lethal infections in wild primates.
AB  - Non-lethal parasite infections are common in wildlife, but there is little
      information on their clinical consequences. Here, we pair infection data from a
      ubiquitous soil-transmitted helminth, the whipworm (genus Trichuris), with
      activity data from a habituated group of wild red colobus monkeys (Procolobus
      rufomitratus tephrosceles) in Kibale National Park, Uganda. We use mixed-effect
      models to examine the relationship between non-lethal parasitism and red colobus
      behaviour. Our results indicate that red colobus increased resting and decreased
      more energetically costly behaviours when shedding whipworm eggs in faeces.
      Temporal patterns of behaviour also changed, with individuals switching behaviour
      less frequently when whipworm-positive. Feeding frequency did not differ, but red
      colobus consumption of bark and two plant species from the genus Albizia, which
      are used locally in traditional medicines, significantly increased when animals
      were shedding whipworm eggs. These results suggest self-medicative plant use,
      although additional work is needed to verify this conclusion. Our results
      indicate sickness behaviours, which are considered an adaptive response by hosts
      during infection. Induction of sickness behaviour in turn suggests that these
      primates are clinically sensitive to non-lethal parasite infections.

PMID- 26311671
TI  - Orchid phylogenomics and multiple  drivers of their extraordinary 
      diversification.
AB  - Orchids are the most diverse family of angiosperms, with over 25 000 species,more
      than mammals, birds and reptiles combined. Tests of hypotheses to account for
      such diversity have been stymied by the lack of a fully resolved broad-scale
      phylogeny. Here,we provide such a phylogeny, based on 75 chloroplast genes for 39
      species representing all orchid subfamilies and 16 of 17 tribes, time-calibrated
      against 17 angiosperm fossils. Asupermatrix analysis places an additional 144
      species based on three plastid genes. Orchids appear to have arisen roughly 112
      million years ago (Mya); the subfamilies Orchidoideae and Epidendroideae diverged
      from each other at the end of the Cretaceous; and the eight tribes and three
      previously unplaced subtribes of the upper epidendroids diverged rapidly from
      each other between 37.9 and 30.8 Mya. Orchids appear to have undergone one
      significant acceleration of net species diversification in the orchidoids, and
      two accelerations and one deceleration in the upper epidendroids. Consistent with
      theory, such accelerations were correlated with the evolution of pollinia, the
      epiphytic habit, CAM photosynthesis, tropical distribution (especially in
      extensive cordilleras),and pollination via Lepidoptera or euglossine bees. Deceit
      pollination appears to have elevated the number of orchid species by one-half but
      not via acceleration of the rate of net diversification. The highest rate of net
      species diversification within the orchids (0.382 sp sp(-1) My(-1)) is 6.8 times
      that at the Asparagales crown.

PMID- 26311672
TI  - The brain uses extrasomatic information  to estimate limb displacement.
AB  - A fundamental problem faced by the brain is to estimate whether a touched object
      is rigidly attached to a ground reference or is movable. A simple solution to
      this problem would be for the brain to test whether pushing on the object with a
      limb is accompanied by limb displacement. The mere act of pushing excites large
      populations of mechanoreceptors, generating a sensory response that is only
      weakly sensitive to limb displacement if the movements are small, and thus can
      hardly be used to determine the mobility of the object. In the mechanical world,
      displacement or deformation of objects frequently co-occurs with microscopic
      fluctuations associated with the frictional sliding of surfaces in contact or
      with micro-failures inside an object. In this study,we provide compelling
      evidence that the brain relies on these microscopic mechanical events to estimate
      the displacement of the limb in contact with an object, and hence the mobility of
      the touched object. We show that when pressing with a finger on a stiff surface,
      fluctuations that resemble the mechanical response of granular solids provoke a
      sensation of limb displacement. Our findings suggest that when acting on an
      external object, prior knowledge about the sensory consequences of interacting
      with the object contributes to proprioception.

PMID- 26311673
TI  - Introgressive hybridization facilitates  adaptive divergence in a recent 
      radiation of monkeyflowers.
AB  - A primary goal in evolutionary biology is to identify the historical events that
      have facilitated the origin and spread of adaptations. When these adaptations
      also lead to reproductive isolation, we can learn about the evolutionary
      mechanisms contributing to speciation. We reveal the complex history of the gene
      MaMyb2 in shaping flower colour divergence within a recent radiation of monkey
      flowers.In the Mimulus aurantiacus species complex, red-flowered M. a. ssp.
      puniceus and yellow-flowered M. a. ssp. australis are partially isolated because
      of differences in pollinator preferences. Phylogenetic analyses based on genome
      wide variation across the complex suggest two origins of red flowers from a
      yellow-flowered ancestor: one in M. a. ssp. puniceus and one in M. a.
      ssp.flemingii. However, in both cases, red flowers are caused by cis-regulatory
      mutations in the gene MaMyb2. Although this could be due to distinct mutations in
      each lineage, we show that the red allele in M. a. ssp. puniceus did not evolve
      de novo or exist as standing variation in its yellow-flowered ancestor. Rather,
      our results suggest that a single red MaMyb2 allele evolved during the radiation
      of M. aurantiacus that was subsequently transferred to the yellow-flowered
      ancestor of M. a. ssp. puniceus via introgressive hybridization. Because gene
      flow is still possible among taxa, we conclude that introgressive hybridization
      can be a potent driver of adaptation at the early stages of divergence that can
      contribute to the origins of biodiversity.

PMID- 26311675
TI  - eComment. Pain scales: a tool for assessing post-thoracotomy pain. Is it enough?

PMID- 26311677
TI  - eComment. Complexity of coronary artery disease and outcomes after complete
      revascularization with long segmental reconstruction of the left anterior
      descending artery.

PMID- 26311678
TI  - eComment. The dilemma of coronary endarterectomy.

PMID- 26311679
TI  - eComment. Bowel ischaemia after cardiac surgery.

PMID- 26311680
TI  - eComment. New onset atrial fibrillation induced by adenosine.

PMID- 26311681
TI  - eComment. Is the problem the duration of mechanical ventilation or how it is
      performed?

PMID- 26311682
TI  - eComment. Could we further prevent bronchopleural fistulas after pneumonectomy?

PMID- 26311683
TI  - eComment. Postoperative mechanical ventilation for patients undergoing
      pneumonectomy.

PMID- 26311684
TI  - eComment. Tracheobronchial trauma in lung transplantation: ethical
      considerations.

PMID- 26311687
TI  - Umboniibacter roseus sp. nov., isolated from coastal seawater.
AB  - A Gram-reaction-negative, non-motile, strictly aerobic, dark pink-pigmented and
      rod-shaped bacterial isolate, designated 14-121-B13T, was isolated from surface
      seawater off the coast of the South Sea at Namhae-gun, Republic of Korea. Cells
      were catalase- and oxidase-positive and required NaCl for growth. Strain 14-121
      B13T grew optimally at 30  degrees C, in the presence of 2 % (w/v) NaCl and at pH
      7.5-8.0.Neighbour-joining, maximum-likelihood and maximum-parsimony phylogenetic
      trees based on 16S rRNA gene sequences showed that strain 14-121-B13T clustered
      with the type strain of Umboniibacter marinipuniceus, with which it exhibited
      96.7 % sequence similarity. The DNA G+C content of strain 14-121-B13T was 48.9
      mol%. The major cellular fatty acids were summed feature 3 (C16 : 1omega7c and/or
      C16 : 1omega6c) and C16 : 0. The major respiratory quinone was ubiquinone Q-7 and
      the polar lipids detected in strain 14-121-B13T were diphosphatidylglycerol,
      phosphatidylglycerol, phosphatidylethanolamine, an unidentified aminolipid,
      unidentified phospholipids, unidentified aminophospholipids and unidentified
      lipids. Based on the phenotypic, chemotaxonomic and phylogenetic data presented,
      strain 14-121-B13T is considered to represent a novel species of the genus,
      Umboniibacter for which the name Umboniibacter roseus sp. nov. is proposed. The
      type strain is 14-121-B13T ( = DSM 29882T = KCTC 42467T).

PMID- 26311688
TI  - Vaccine mandates in the US are doing more harm than good.

PMID- 26311689
TI  - Hazard Patterns Associated With Co-sleepers.
AB  - We conducted a retrospective review of incidents associated with co-sleepers. A
      total of 26 incidents (6 deaths and 20 injuries) were reported to the Consumer
      Product Safety Commission. Of these, 5 deaths were caused by asphyxia, and 1 was
      attributed to sudden infant death syndrome (SIDS). The mean age at death was 3.1
      months. Two-thirds of deaths had known risk factors for SIDS. Of the 20 injuries,
      entrapment (60%) and suffocation (35%) hazards were most common. Almost half of
      the injuries occurred after the co-sleeper was improperly assembled. Infant
      deaths and injuries associated with co-sleepers are infrequent. Most deaths were
      associated with other SIDS risk factors. Many deaths and injuries were associated
      with improper use or assembly of the co-sleeper. It is important for
      pediatricians to advise parents not to use previously owned co-sleepers or to use
      co-sleepers in any way other than what is specifically stated in the product
      instructions to avoid infant injury or death.

PMID- 26311690
TI  - Vascular biomarkers derived from dynamic contrast-enhanced MRI predict response
      of vestibular schwannoma to antiangiogenic therapy in type 2 neurofibromatosis.
AB  - BACKGROUND: Antiangiogenic therapy of vestibular schwannoma (VS) in type 2
      neurofibromatosis can produce tumor shrinkage with response rates of 40%-60%.
      This study examines the predictive value of parameter-derived MRI in this
      setting. METHODS: Twelve patients with 20 VSs were recruited. Each had at least
      one rapidly growing tumor. Patients were treated with bevacizumab, 5 mg/kg every
      2 weeks. Patients with stable or reduced VS volume were maintained at 2.5-5 mg
      every 4 weeks after 6 months. Those who failed treatment had their bevacizumab
      discontinued. Dynamic contrast-enhanced (DCE) MRI performed prior to treatment
      using a high temporal resolution technique, and data were analyzed to allow
      measurement of contrast transfer coefficient (K(trans)), vascular fraction
      (v(p)), extravascular-extracellular fraction (v(e)). Relaxation rate (R1(N)) was
      measured using a variable flip angle technique. Apparent diffusional coefficient
      (ADC) was calculated from diffusion-weighted imaging. The predictive power of
      microvascular parameters and ADC were examined using logistic regression
      modeling. RESULTS: Responding tumors were larger (P < .001), had lower R1(N) (P <
      .001), and higher K(trans) (P < .05) and ADC (P < .01). They showed increases in
      R1(N) (P < .01) and reduction of K(trans) (P < .01) and ADC (P < .01). Modeling
      to predict response demonstrated significant independent predictive power for
      R1(N) (Beta = - 0.327, P < .001), and K(trans) (Beta = 0.156, P < .05). Modeling
      to predict percentage change in tumor volume at 90 days identified baseline tumor
      volume (Beta = 5.503, P < .05), R1(N) (Beta = - 5.844, P < .05), and K(trans)
      (Beta = 5.622, P < .05) as independent significant predictors. CONCLUSIONS: In
      patients with type 2 neurofibromatosis, biomarkers from DCE-MRI are predictive of
      VS volume response to inhibition of vascular endothelial growth factor
      inhibition.

PMID- 26311691
TI  - The challenge of unreported and unprogrammed deworming for soil-transmitted
      helminth control programs.
AB  - Soil-transmitted helminthiasis (STH) affects more than one billion people
      worldwide. WHO aims to control STH as a public health problem by providing
      periodic anthelminthic treatment to >=75% of all at-risk children. Tracking
      progress toward this 2020 goal relies on accurate reporting of drug coverage. For
      STH, this is difficult because an unknown-but substantial-proportion of deworming
      occurs outside nationally-administered STH control programs, so-called
      'unprogrammed deworming.' Further, coordination of intersectoral efforts needed
      to administer drugs to different risk groups-and to report coverage to WHO-is
      inadequate. This paper describes these challenges and offers suggestions to
      overcome them. 

PMID- 26311692
TI  - [To attach importance of basic research in Muller cell of diabetic retinopathy].
AB  - Retina is the classic "neurovascular coupling" tissue, and coordinate the
      bioactivity of neurobiology and retinal blood flow. Muller glia cells span the
      entire thickness of the tissue, and ensheath all retinal neurons and
      microvascular of the retina. This morphological relationship is reflected by a
      multitude of functional interactions between neurons and blood-retinal barrier,
      and play fundamental roles in diabetic retinopathy. However, in recent studies,
      the mechanisms of Muller glia cells in retinal neurodegeneration and
      microcirculatory abnormalities of diabetic retinopathy are underestimating.
      Therefore, the present article reaffirms the interrelationship between Muller
      glia cells and diabetic retinopathy to draw the attentions of researchers. 

PMID- 26311693
TI  - [The association of variable number of tandem repeats polymorphism in the
      endothelial nitric oxide synthase gene and diabetic retinopathy].
AB  - OBJECTIVE: To investigate the association between the variable number of tandem
      repeats (VNTR) polymorphism 4a/b in the endothelial nitric oxide synthase (eNOS)
      gene and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus.
      METHODS: cross-sectional study. A total of 278 type 2 diabetes patients were
      recruited, of whom 130 had DR, and 148 had diabetes without retinopathy (DWR). Of
      the 130 patients with DR, 34 had proliferative DR (PDR) and 96 had non
      proliferative DR (NPDR). A number of 223 volunteers without diabetes from the
      same area were recruited as the control group. PCR and agarose gel
      electrophoresis methods were adopted to determine the 4a/b polymorphism genotypes
      of the eNOS gene. Statistical analysis was performed using the R statistical
      analysis package. Genotype distribution was compared using the chi(2) test.
      Numerical data were examined by Student t test. Genotypes and allele frequencies
      between cases and controls were compared using the chi(2) test or Fisher's exact
      test. Odd ratios (OR) and 95% confidence intervals (CI) were calculated according
      to the Woolf's equation. RESULTS: The frequencies of minor alleles (a) were 10.8%
      and 11.5% in the DR and DWR group, respectively. There were no statistical
      differences between the two groups (chi(2) = 0.07, P = 0.789). Also there were no
      statistical differences (chi(2) = 0.88; P = 0.643) in the distributions of the
      genotypes between DR group (bb 78.5%, ab 21.5%, aa 0.0%) and DWR group (bb 77.7%,
      ab 21.6%, aa 0.7%). Statistical differences were found in the frequencies of
      alleles, and the distributions of genotypes between diabetes group and the
      control group (chi(2) = 8.75, 10.39, P = 0.003, 0.006). However, after adjustment
      for age, blood pressure, cholesterol concentration, blood-fat and so on, it
      became insignificant (chi(2) = 0.97, 1.25, P = 3.224, 0.812). In the multiple
      regressions model including clinic factors such as the age of onset of diabetes,
      urinary albumin, insulin using, creatinine, glycated hemoglobin and fast glucose,
      no evidence showed that eNOS gene VNTR 4a/b was associated with diabetic
      retinopathy (OR = 0.37, 95% CI: 0.15-0.95). CONCLUSION: There was no significant
      association between eNOS gene VNTR 4a/b polymorphism and diabetic retinopathy
      (DR) in patients with type 2 diabetes mellitus.

PMID- 26311694
TI  - [Targeting VEGF siRNA transfection by new polymeric liposomes to inhibit retinal
      neovascularization].
AB  - OBJECTIVE: To formulate and evaluate polymeric liposomes (PL) nanoparticles as a
      novel non-viral gene delivery. To explore its applicability and feasibility as a
      non-viral vector for gene transportation. METHOD: Experimental study. To
      construct the orongoxygen induced retinopathy (OIR) mouse (C57BL/6J) model on the
      basis of improved Smith's methods. Western blot was used to measure VEGF protein
      expression in retinal tissue at P17 and P22. HE staining and fluorescein-dextran
      angiography of retinal vascular were performed to observe the morphologic
      alterations of retinal neovascularization. Frozen-section was used to show the
      membrane translocation of PL. RESULTS: In fluorescence angiograms, irregular
      neovascularization and fluoresce leakage were observed in OIR model. The results
      of Western blot showed that VEGF protein in retinal tissues were significantly
      different among groups (F = 158.207, P = 0.000) at P17 and P22 (F = 25.695, P =
      0.000). The protein level was lower in both PL (0.70 +/- 0.03) and Lipo group
      (0.66 +/- 0.04) at P17 (P = 0.092), and the lower level was presented at P22 in
      PL group (0.50 +/- 0.03) than in Lipo group (0.53 +/- 0.05) (P < 0.05). HE
      staining were performed to observe the significantly improvements of retinal
      neovascularization in PL (28.0 +/- 3.44) and Lipo group (24.50 +/- 3.06) at P17.
      Moreover, inhibitory effects maintained at P22 in PL group (11.70 +/- 3.09) as HE
      staining showed. Fluorescein angiography of retinal vascular showed retinal non
      perfusion and neovascularization areas were smaller in both PL and Lipo group at
      P17. Frozen-section examination showed the property of membrane translocation.
      GFP expression could be seen in vitreous cavity just at first day post
      intravitreal administration in PL and Lipo group, which could reach their peaks
      in external retina nearby RPE layer at P17, remaining at P22 in PL group.
      CONCLUSION: The PL performed excellent ability of membrane translocation and it
      was a kind of slow steady released gene vector.

PMID- 26311695
TI  - [The mediation of HIF-1alpha siRNA to the leukocyte adhesion and myeloid cell's
      activity in rat's retina under early stage of diabetic retinopathy].
AB  - OBJECTIVE: To investigate the mediation of HIF-1alpha siRNA to the leukocyte
      adhesion and myeloid cell's activity in rat's retina at early stage of diabetic
      retinopathy. METHODS: Experimental study. HIF-1alpha specific siRNA expression
      vector pSUPERH1-siHIF1alpha was constructed by gene recombination. The rat
      diabetic model was induced by intraperitoneal injection of streptozotocin. After
      2 months of diabetes induction, 27 diabetic rats were randomly chosen and
      assigned to 3 groups, including diabetes and phosphate buffered saline (PBS)
      vitreous injection group (group B), diabetes and pSUPERH1-siHIF1alpha vitreous
      transfect group (group C) and diabetes and pSUPER-retro vitreous transfect group
      (group D). Each group had 9 rats. Nine age matched health rats were chosen as
      control group (group A). Retinal leukostasis was quantified with acridine orange
      leukocyte fluorography. Retinal myeloid cell activity was measured by enzyme
      linked immunosorbent assay of myeloperoxidase (MPO). The differences of the mean
      values among the four groups were analyzed by one-factor analysis of variance.
      The multiple comparisons of the mean values among the four groups were analyzed
      by LSD-t analysis. RESULTS: According to the results of the acridine orange
      leukocyte fluorography, the numbers of leukocyte adhesion in the four groups were
      (47.00 +/- 3.60), (155.33 +/- 9.01), (76.00 +/- 9.05), (142.66 +/- 10.26),
      respectively. The differences among them were significant (F = 116.25, P = 0.00).
      The number of leukocyte adhesion in the group C was significantly lower than that
      in group B (LSD-t test, P = 0.00, 95% CI: 3.56-95.10). The levels of retinal MPO
      in the four groups were (17.24 +/- 1.13), (31.32 +/- 2.53), (21.35 +/- 1.06),
      (31.33 +/- 1.26) ug/L, respectively. The differences among them were significant
      (F = 58.68, P = 0.00). The level of retinal MPO in the group C was significantly
      lower than that in group B (LSD-t test, P = 0.00, 95% CI: 6.92-13.01).
      CONCLUSIONS: HIF-1alpha siRNA may play a role in the mediation of the leukocyte
      adhesion and myeloid cell's activity in rat's retina at early stage of diabetic
      retinopathy in vivo.

PMID- 26311696
TI  - [Retina penetration of subconjunctival ranibizumab injection in the rabbit eye].
AB  - OBJECTIVE: To investigate whether ranibizumab can penetrate into the retina after
      subconjunctival injection in a rabbit model. METHODS: Experimental study. Fifty
      six New Zealand rabbits were randomly divided into four groups: control group
      (3), saline subconjunctival injection group (3), ranibizumab intravitreal
      injection group (25) and ranibizumab subconjunctival injection group (25). Each
      rabbit received single injection in right eye. Ranibizumab's location and
      concentrations in the retina and aqueous humor were determined by
      immunofluorescence staining and ELISA at 1, 2, 4, 8, 12 weeks after injection.
      The comparison of ranibizumab concentration data was analyzed by t-test. RESULTS:
      The concentrations of aqueous humor in intravitreal injection group, determined
      by ELISA, were (389.67 +/- 22.55), (319.33 +/- 17.93), (22.67 +/- 3.06), (9.67 +/
      1.53) and (7.33 +/- 2.18) mg/L at 1, 2, 4, 8, 12 weeks respectively.
      Concentrations of subconjunctival injection group were (53.67 +/- 3.21), (12.67
      +/- 3.06), (8.33 +/- 1.53), (2.66 +/- 2.08) mg/L at 1,2,4,8 weeks and had a
      statistical difference compared with intravitreal injection group at each time
      point (t = 32.96, 38.39, 7.67, 11.07, P < 0.05). But there was no detection at 12
      weeks. Similar in retina immunofluorescence staining results, the ranibizumab
      positive signals were detected in all the time points except the last one in
      subconjunctival injection group. CONCLUSION: Subconjunctival ranibizumab
      injection may be able to penetrate into retina.

PMID- 26311697
TI  - [Analysis of the NDP gene in a Chinese family with X-linked recessive Norrie
      disease].
AB  - OBJECTIVE: The purpose of the current research was to investigate the NDP (Norrie
      disease protein) gene in one Chinese family with Norrie disease (ND) and to
      characterize the related clinical features. METHODS: Clinical data of the proband
      and his family members were collected. Complete ophthalmic examinations were
      carried out on the proband. Genomic DNA was extracted from peripheral blood
      leukocytes of 35 family members. Molecular analysis of the NDP gene was performed
      by polymerase chain reaction and direct sequencing of all exons and flanking
      regions. RESULTS: A hemizygous NDP missense mutation c.362G > A (p.Arg121Gln) in
      exon 3 was identified in the affected members, but not in any of the unaffected
      family individuals. CONCLUSIONS: The missense mutation c.362G > A in NDP is
      responsible for the Norrie disease in this family. This discovery will help
      provide the family members with accurate and reliable genetic counseling and
      prenatal diagnosis.

PMID- 26311698
TI  - [Ophthalmic manifestations in acquired immune deficiency syndrome patients with
      cryptococcal meningitis].
AB  - OBJECTIVE: Analysis ophthalmic manifestations in acquired immune deficiency
      syndrome (AIDS) patients with cryptococcal meningitis. METHODS: Retrospective
      study. Forty AIDS patients (including 32 men and 8 women) with cryptococcal
      meningitis were studied. The age of the patients varied from 11 to 67 years,
      average on (38 +/- 12) years (mean +/- standard deviation). All the patients
      underwent detailed ocular examinations including corrected visual acuity, eye
      movement, intraocular pressure, slit lamp microscope, indirect ophthalmoscope and
      color fundus photography. The CD4(+) T cell count was evaluated and Lumbar
      puncture was done to examine the cerebral spinal fluid (CSF). Eighteen patients
      were followed up for a period between 2 weeks to 4 years. Four patients died
      during hospitalization. The remaining 18 patients failed to be followed up due to
      moving away. RESULTS: Binocular diplopia were present in 3 patients. It showed
      Binocular or monocular abducens nerve palsy. Papilledema were found in 37 eyes of
      19 cases. One person had unilateral papilledema. Among 19 cases, 24 eyes of 12
      cases were accompanied with peripapillary hemorrhages and 7 cases of 13 eyes
      without peripapillary hemorrhages. Optic atrophy occurs in 6 cases of 12 eyes and
      multifocal choroiditis in 2 cases of 4 eyes. Twenty-seven eyes of 14 patients had
      normal fundus or cytomegalovirus retinitis (CMVR) only. CONCLUSIONS: AIDS
      patients with cryptococcal meningitis merger may be accompanied by a variety of
      eye complications. Papilledema are the most common manifestations.

PMID- 26311699
TI  - [Contributions of human rods and cones pathway to different components of
      oscillatory potentials in time and frequency domain].
AB  - OBJECTIVE: To investigate the contributions of human rods and cones pathway to
      different components of oscillatory potentials (OP) in time and frequency domain.
      METHODS: Case-control study. Twenty subjects were divided into two groups, normal
      groups (NG) and cones pathway abnormal groups (CAG). All eyes were investigated
      by dark-adapted (DA) and light-adapted (LA) 3.0 ERG recommended by ISCEV. Data
      were output into the computer and processed and analyzed by the software
      Matlab7.0. First, to extract the OP by filter, then to get the frequency
      amplitude relationship by FFT, after that the relationship was fitted by
      equations and lastly we statistic and analyze the parameters gotten from the
      equations. RESULTS: Compared with normal group [(48.63 +/- 4.29), (158.00 +/-
      32.75), (69.27 +/- 30.31), (38.5 +/- 15.28) uV], the amplitudes of the first two
      components of dark-adapted OP in the CAG [(4.12 +/- 3.20), (71.25 +/- 25.43),
      (48.96 +/- 20.05), (36.84 +/- 14.26) uV] were significant decreased (t = 16.68,
      5.77, P < 0.01). Frequency domain of LA and DA OP in the two groups was comprised
      with two components (harmonic and subharmonic). Compared with normal group,
      harmonic components of CAG were dramatic decreased (t = 2.72, P < 0.05; Z = 
      2.24, P < 0.05). The value of subharmonic component in CAG was lowest in DA OP
      compared with NG (t = 4.20, P < 0.005). CONCLUSIONS: Cones and rods pathway all
      contributed to the DA and LA OP Cones pathway mainly contributes to the earlier
      and faster components of OP while the rods pathway to the later and slower
      components.

PMID- 26311700
TI  - [Research advance of retinal pathological angiogenesis related to ATM protein
      kinase].
AB  - Ataxia-telangiectasia mutated (ATM) gene could cause ataxia telangiectasia which
      is an autosomal recessive disease. The ATM protein kinase encoded by the ATM gene
      mainly distributed in nucleus as a master regulator of the DNA damage response
      and apoptosis via cell signaling pathways. The ATM kinase plays a key role in the
      pathogenesis of cellular senescence and tumor genesis. Recently, some studies
      have indicated that ATM protein kinase is involved in pathological
      neovascularization, suggesting that it could be a novel potential therapeutic
      target in diseases associated with pathological angiogenesis. 

PMID- 26311701
TI  - [Exome sequencing in the research of genetic eye diseases].
AB  - There are a variety of genetic eye diseases. In the past years, many methods such
      as linkage analysis and association analysis have been used to study these
      diseases and lots of achievements have been made. With the development of the
      second-generation sequencing technology, DNA sequencing has become much more
      efficient and cheaper. Exome trapping, combining with the second-generation
      sequencing technology, has become efficient and accurate means to sequence DNA
      and screen disease-causing genes. This review outlines the research progresses in
      eye inherited diseases, the methodological characteristics of second-generation
      sequencing and exome trapping and their applications in genetic eye diseases. 

PMID- 26311702
TI  - Monte Carlo simulation of secondary radiation exposure from high-energy photon
      therapy using an anthropomorphic phantom.
AB  - The development of intensity-modulated radiotherapy treatments delivering large
      amounts of monitor units (MUs) recently raised concern about higher risks for
      secondary malignancies. In this study, optimised combinations of several variance
      reduction techniques (VRTs) have been implemented in order to achieve a high
      precision in Monte Carlo (MC) radiation transport simulations and the calculation
      of in- and out-of-field photon and neutron dose-equivalent distributions in an
      anthropomorphic phantom using MCNPX, v.2.7. The computer model included a Varian
      Clinac 2100C treatment head and a high-resolution head phantom. By means of the
      applied VRTs, a relative uncertainty for the photon dose-equivalent distribution
      of <1 % in-field and 15 % in average over the rest of the phantom could be
      obtained. Neutron dose equivalent, caused by photonuclear reactions in the linear
      accelerator components at photon energies of approximately >8 MeV, has been
      calculated. Relative uncertainty, calculated for each voxel, could be kept below
      5 % in average over all voxels of the phantom. Thus, a very detailed neutron dose
      distribution could be obtained. The achieved precision now allows a far better
      estimation of both photon and especially neutron doses out-of-field, where
      neutrons can become the predominant component of secondary radiation. 

PMID- 26311703
TI  - 2240 IRRADIATED PERSONAL DOSEMETERS FOR THE IC2014 EURADOS INTERCOMPARISON AT
      SEIBERSDORF.
AB  - The Dosimetry Laboratory Seibersdorf was the irradiation laboratory for the
      IC2014 EURADOS intercomparison for individual monitoring. One hundred and twelve
      whole-body dosimetry systems with 30 dosemeters per dosimetry system participated
      in the intercomparison. In total, 2240 personal dosemeters were irradiated in
      photon reference radiation fields on the ISO water slab phantom in terms of
      personal dose equivalent Hp(10) and Hp(0.07). Two nuclide irradiation systems
      ((137)Cs and (60)Co gamma radiation) and a 320-kV X-ray radiation unit were used.
      The irradiation plan consisted of nine irradiation set-ups with five different
      ISO/IEC photon radiation qualities (S-Cs, S-Co, RQR 7, W-80 and W-150) and two
      different angles of radiation incidence (0 degrees  and 60 degrees ). Reference
      dose equivalent values were in the range of ~1-500 mSv. Reference values were
      based on air kerma rate traceable to primary standard calibrations and
      appropriate conversion coefficients resulting in total expanded measurement
      uncertainties <6 %. 

PMID- 26311704
TI  - Factors associated with GPs' knowledge of their patients' socio-economic
      circumstances: a multilevel analysis.
AB  - BACKGROUND: To determine appropriate management for individual patients, GPs are
      supposed to use their knowledge of the patient's socio-economic circumstances.
      OBJECTIVE: To analyse factors associated with GPs' knowledge of these
      circumstances. METHODS: Observational survey of GPs who were internship
      supervisors in the Paris metropolitan area. Each of 52 volunteer GPs completed a
      self-administered questionnaire about their own characteristics and randomly
      selected 70 patients from their patient list. Their knowledge was analysed as the
      agreement between the patients' and GPs' responses to questions about the
      patients' socio-economic characteristics in questionnaires completed by both
      groups. The association between agreement and the GPs' characteristics was
      analysed with a multilevel model adjusted for age, sex and the duration of the GP
      patient relationship. RESULTS: Agreement varied according to the socio-economic
      characteristics considered (from 51% to 90%) and between GPs. Globally, the GPs
      overestimated their patients' socio-economic level. GP characteristics associated
      with better agreement were sex (female), long consultations, the use of paper
      records or an automatic reminder system and participation in continuing medical
      education and in meetings to discuss difficult cases. CONCLUSION: Knowledge of
      some patient characteristics, such as their complementary health insurance
      coverage or perceived financial situation, should be improved because their
      overestimation may lead to care that is too expensive and thus result in the
      patients' abandonment of the treatment. Besides determining ways to help GPs to
      organize their work more effectively, it is important to study methods to help
      doctors identify their patients' social-economic circumstances more accurately in
      daily practice.

PMID- 26311705
TI  - Collaboration and communication in colorectal cancer care: a qualitative study of
      the challenges experienced by patients and health care professionals.
AB  - BACKGROUND: Colorectal cancer is becoming a chronic condition. This has
      significant implications for the delivery of health care and implies the
      involvement of a range of health care professionals (HCPs) from different
      settings to ensure the needed quality and continuity of care. OBJECTIVES: To
      explore the challenges that patients and HCPs experience in the course of
      colorectal cancer care and the perceived consequences caused by these challenges.
      METHODS: Ten semi-structured focus groups were conducted including patients
      receiving treatment for colorectal cancer, representatives of patient support
      groups, physicians and other non-physician HCPs from different health care
      settings. Participants were asked to share their experiences regarding colorectal
      cancer care. All data were audio- and videotaped, transcribed verbatim and
      thematically analysed using qualitative content analysis. RESULTS: Patients and
      HCPs (total N = 47) experienced collaboration and communication as well as
      exchange of information between HCPs as challenging. Particularly communication
      and information exchange with GPs appeared to be lacking. The difficulties
      identified restricted a well-working coordination of care and seemed to cause
      inappropriate health care. CONCLUSION: Colorectal cancer care seems to require an
      effective, well-working collaboration and communication between the different
      HCPs involved ensuring the best possible care to suit patients' individual needs.
      However, the perceived challenges and consequences of our participants seem to
      restrict the delivery of the needed quality of care. Therefore, it seems crucial
      (i) to include all HCPs involved, especially the GP, (ii) to support an efficient
      and standardized exchange of health-related information and (iii) to focus on the
      patients' entire pathway of care.

PMID- 26311706
TI  - Diagnosis and management of type 1 diabetes in adults: summary of updated NICE
      guidance.

PMID- 26311707
TI  - Effects of Chios mastic gum on cholesterol and glucose levels of healthy
      volunteers: A prospective, randomized, placebo-controlled, pilot study (CHIOS
      MASTIHA).
AB  - BACKGROUND: Chios mastic gum (CMG) possesses anti-oxidant, anti-inflammatory,
      anti-atheromatic, lipid- and glucose-lowering properties. We evaluated the
      effects of CMG on cholesterol and fasting plasma glucose (FPG) levels of healthy
      volunteers. DESIGN: A prospective, randomized, placebo-controlled, pilot study.
      METHODS: One hundred and seventy nine volunteers with total cholesterol levels
      >200 mg/dl were randomized to four groups. Finally, 156 volunteers completed the
      follow-up period and were analysed: (1) control group (C, n = 23), receiving
      placebo; (2) total mastic (TM, n = 72) receiving daily a total dose of 1 g of
      crude CMG (330 mg capsules, tid); (3) polymer-free mastic (PFM, n = 33),
      receiving daily a total dose of 1 g of polymer free mastic (330 mg caps, tid);
      and (4) powder mastic (PM, n = 28), receiving daily a total dose of 2 g of crude
      CMG. RESULTS: After eight weeks, the TM group reduced total cholesterol by 11.5
      mg/dl (p < 0.05) and FPG by 4.5 mg/dl (p < 0.05) adjusted for age, gender, BMI
      and baseline characteristics. The effect was stronger in overweight and obese
      patients (BMI > 25), with an estimated mean reduction of total cholesterol by
      13.5 mg/dl (p < 0.05) and FPG by 5.1 mg/dl (p < 0.05). Administration of PFM and
      PM resulted in no statistically significant alteration. No effect was observed on
      LDL, HDL, triglycerides, uric acid and CRP. No gastrointestinal, liver or renal
      adverse events were recorded. CONCLUSIONS: CMG has a significant lowering effect
      on total cholesterol and glucose levels of healthy volunteers, with excellent
      tolerance and no detectable side effects, especially in overweight and obese
      individuals.

PMID- 26311708
TI  - Manganese phytotoxicity: new light on an old problem.
AB  - BACKGROUND: Manganese (Mn) is an essential micronutrient that is phytotoxic under
      certain edaphic and climatic conditions. Multiple edaphic factors regulate Mn
      redox status and therefore its phytoavailability, and multiple environmental
      factors including light intensity and temperature interact with Mn phytotoxicity.
      The complexity of these interactions coupled with substantial genetic variation
      in Mn tolerance have hampered the recognition of Mn toxicity as an important
      stress in many natural and agricultural systems. SCOPE: Conflicting theories have
      been advanced regarding the mechanism of Mn phytotoxicity and tolerance. One line
      of evidence suggests that Mn toxicity ocurrs in the leaf apoplast, while another
      suggests that toxicity occurs by disruption of photosynthetic electron flow in
      chloroplasts. These conflicting results may at least in part be attributed to the
      light regimes employed, with studies conducted under light intensities
      approximating natural sunlight showing evidence of photo-oxidative stress as a
      mechanism of toxicity. Excessive Mn competes with the transport and metabolism of
      other cationic metals, causing a range of induced nutrient deficiencies.
      Compartmentation, exclusion and detoxification mechanisms may all be involved in
      tolerance to excess Mn. The strong effects of light, temperature, precipitation
      and other climate variables on Mn phytoavailability and phytotoxicity suggest
      that global climate change is likely to exacerbate Mn toxicity in the future,
      which has largely escaped scientific attention. CONCLUSIONS: Given that Mn is
      terrestrially ubiquitous, it is imperative that the heightened risk of Mn
      toxicity to both managed and natural plant ecosystems be factored into evaluation
      of the potential impacts of global climate change on vegetation. Large inter- and
      intraspecific genetic variation in tolerance to Mn toxicity suggests that
      increased Mn toxicity in natural ecosystems may drive changes in community
      composition, but that in agroecosystems crops may be developed with greater Mn
      tolerance. These topics deserve greater research attention.

PMID- 26311709
TI  - Secondary phloem diversity and evolution in Bignonieae (Bignoniaceae).
AB  - BACKGROUND AND AIMS: Phloem evolution has been explored in the literature across
      very broad scales, either for vascular plants as a whole or for major plant
      groups, such as the monocotyledons or the former dicotyledons. However, it has
      never been examined in a way that would elucidate evolutionary shifts leading to
      the diversification of phloem in single lineages. Therefore, the present study
      explores in detail the patterns of phloem evolution in the tribe Bignonieae
      (Bignoniaceae). This group represents a particularly good model for phloem
      studies since it is known to have a very conspicuous and diverse phloem. METHODS:
      A total of 19 phloem characters were coded in 56 species from all 21 genera
      currently recognized in the tribe Bignonieae, accounting for phloem wedge growth
      and for all the anatomical cell diversity encountered in the phloem. Phloem
      evolution was explored by reconstructing ancestral character states using maximum
      likelihood assumptions with a time-calibrated molecular phylogeny for the group.
      Directionality and the effect of phylogenetic transformations in the current
      variation of quantitative traits and evolutionary correlations of selected
      discrete phloem traits were also tested under a maximum-likelihood approach. KEY
      RESULTS: Individual phloem features are quite diverse in the tribe, but generally
      conserved within smaller clades. Contrasting phloem patterns were found when
      comparing major groups, with certain lineages having the phloem marked by a
      background of phloem fibres where all other cells are embedded, tangentially
      arranged sieve tubes and sieve-tubecentric parenchyma. In contrast, other
      lineages exhibited a scarcely fibrous phloem, regularly stratified phloem, sieve
      tube elements in radial or diffuse arrangement, and diffuse parenchyma. We found
      signals of directional evolution in fibre abundance and number of sieve areas,
      which increased in the 'Fridericia and allies extended clade' and decreased in
      the 'Multiples of four extended clade', resulting in no signal of directionality
      when the whole Bignonieae was considered. In contrast, no indication of
      directional evolution was found for the axial parenchyma, either in single clades
      within Bignonieae or in the entire tribe. Positive correlation was found between
      sieve element length and both sieve plate type and the presence of a storied
      structure. Correlated evolution was also found between fibre abundance and
      several traits, such as sieve tube arrangement, sieve plate type, parenchyma
      arrangement, ray lignification and number of companion cells. CONCLUSIONS: The
      secondary phloem of Bignonieae is extremely diverse, with sister lineages
      exhibiting distinct phloem anatomies derived from contrasting patterns of
      evolution in fibre abundance. Fibre abundance in the tribe has diversified in
      correlation with sieve tube arrangement, sieve tube morphology, number of
      companion cells and parenchyma type. The results challenge long-standing
      hypotheses regarding general trends in cell abundance and morphological cell
      evolution within the phloem, and demonstrate the need to expand studies in phloem
      anatomy both at a narrow taxonomic scale and at a broad one, such as to families
      and orders.

PMID- 26311710
TI  - Orchid conservation: making the links.
AB  - Orchidaceae, one of the largest families of flowering plants, present particular
      challenges for conservation, due in great part to their often complex
      interactions with mycorrhizal fungi, pollinators and host trees. In this
      Highlight, we present seven papers focusing on orchids and their interactions and
      other factors relating to their conservation. 

PMID- 26311712
TI  - Characterization of the Left-Sided Substrate in Arrhythmogenic Right Ventricular
      Cardiomyopathy.
AB  - BACKGROUND: The correlates of left ventricular (LV) substrate in arrhythmogenic
      right ventricular (RV) cardiomyopathy are largely unknown. METHODS AND RESULTS:
      Thirty-two patients with arrhythmogenic RV cardiomyopathy (47+/-14 years; 6
      women) were included. RV and LV dysplasia were defined from multidetector
      computed tomography and cardiac magnetic resonance imaging. Arrhythmias were
      characterized as right-sided or left-sided on 12-lead ECG recordings at baseline
      and during isoproterenol testing. In 14 patients, the imaging substrate was
      compared with voltage mapping and local abnormal ventricular activity. Imaging
      abnormalities were found in 32 (100%) and 21 (66%) patients on the RV and LV,
      respectively, intramyocardial fat on multidetector computed tomography being the
      most sensitive feature. LV involvement related to none of the Task Force
      criteria. Right-sided arrhythmias were more frequent than left-sided arrhythmias
      (P=0.003) although the latter were more frequent in case of LV involvement
      (P=0.02). The agreement between low voltage and fat on multidetector computed
      tomography was high on the RV when using either endocardial unipolar or
      epicardial bipolar data (kappa=0.82 and kappa=0.78, respectively) but lower on
      the LV (kappa=0.54 for epicardial bipolar). LV local abnormal ventricular
      activity was found in all patients with LV involvement, and none of the others.
      The density of local abnormal ventricular activity within fat areas was similar
      between the RV and LV (P=0.57). CONCLUSIONS: LV substrate is frequent in
      arrhythmogenic RV cardiomyopathy, but poorly identified by current diagnostic
      strategies. Left-sided arrhythmias are more frequent in case of LV involvement.
      LV fat hosts the same density of local abnormal ventricular activity as RV fat,
      but is less efficiently detected by voltage mapping. These results support the
      need for alternative diagnostic strategies to identify LV dysplasia.

PMID- 26311713
TI  - Surgical clipping versus endovascular coiling for elderly patients presenting
      with subarachnoid hemorrhage.
AB  - BACKGROUND: The comparative effectiveness of the two treatment options (surgical
      clipping and endovascular coiling) for ruptured cerebral aneurysms has not been
      studied in real-world practice in the USA. We investigated the association
      between the treatment method for ruptured cerebral aneurysms and outcomes.
      METHODS: We performed a retrospective cohort study of elderly patients who
      underwent treatment for ruptured cerebral aneurysms from 2007 to 2012 using a
      100% sample of Medicare fee-for-service claims data. An instrumental variable
      analysis was used to control for unmeasured confounding and to create pseudo
      randomization on the treatment method. In sensitivity analysis, controlling only
      for measured confounding, we used propensity score conditioning and inverse
      probability weighting with mixed effects to account for clustering at the
      Hospital Referral Region (HRR) level. RESULTS: During the study period 3210
      patients underwent treatment for ruptured cerebral aneurysms and met the
      inclusion criteria. Of these, 1206 (37.6%) had surgical clipping and 2004 (62.4%)
      had endovascular coiling. Instrumental variable analysis demonstrated no
      difference between coiling and clipping in 1-year postoperative mortality (OR
      1.04; 95% CI 0.70 to 1.54), likelihood of discharge to rehabilitation (OR 1.07;
      95% CI 0.72 to 1.58), or 30-day readmission rate (OR 1.44; 95% CI 0.70 to 1.87).
      However, clipping was associated with 2.7 days longer length of stay (LOS) (95%
      CI 0.45 to 4.99). The same associations were present in propensity score adjusted
      and inverse probability weighted models. CONCLUSIONS: In a cohort of Medicare
      patients, we did not demonstrate a difference in mortality, rate of discharge to
      rehabilitation, and readmissions between clipping and coiling of ruptured
      cerebral aneurysms. Clipping was associated with a slightly longer LOS.

PMID- 26311714
TI  - Treatment of experimental aneurysms with a new liquid embolic agent and a
      retrievable stent: proof of concept and feasibility study.
AB  - BACKGROUND: Occlusion of canine bifurcation and sidewall aneurysms was undertaken
      with a new liquid embolic agent (PHIL 35) assisted by a high-density partially
      retrievable stent (FRED) with preservation of the carotid artery. METHODS: Three
      dogs were used as acute preparations for development of the technique and two
      were used for chronic studies lasting 90 days. In one animal we intentionally did
      not completely fill the aneurysm to determine the long-term results of incomplete
      treatment. The degree of occlusion, carotid artery compromise, and dislodgement
      and/or migration of embolic material in treated aneurysms were assessed. RESULTS:
      All aneurysms planned for complete obliteration were totally occluded
      successfully. By design, we partially occluded one aneurysm. In this aneurysm,
      angiography performed at 30 days revealed less filling, but at 90 days it had
      persistent small residual filling. We did not detect any distal embolization
      during the injection and no angiographic occlusions, change in configuration, or
      delayed migration of the embolic material were found. In the inspected stent, no
      foreign material was noted. In four animals we successfully removed the stent
      with preservation of the integrity of the carotid artery. In the fifth we
      intentionally left both stents deployed. CONCLUSIONS: We have developed a new
      treatment for cerebral aneurysms using a combination of a retrievable stent and a
      new liquid embolic agent.

PMID- 26311715
TI  - Fuming about e-cigarettes and harm.

PMID- 26311716
TI  - Surveillance endoscopy is associated with improved outcomes of oesophageal
      adenocarcinoma detected in patients with Barrett's oesophagus.
AB  - BACKGROUND: The effectiveness of surveillance endoscopy in patients with
      Barrett's oesophagus (BE) for reducing oesophageal adenocarcinoma (EAC)-related
      mortality in patients with BE is unclear. METHODS: This is a cohort study of
      patients with BE diagnosed in the National Veterans Affairs hospitals during 2004
      2009 excluding those with conditions that affect overall survival. We identified
      those diagnosed with EAC after BE diagnosis through 2011 and conducted chart
      reviews to identify BE surveillance programme, and indication for EAC diagnosis,
      verify diagnosis, stage, therapy and cause of death. We examined the association
      between surveillance indication for EAC diagnosis with or without surveillance
      programme and EAC stage and treatment receipt in logistic regression models, and
      with time to death or cancer-related death using a Cox proportional hazards
      regression model. RESULTS: Among 29 536 patients with BE, 424 patients developed
      EAC during a mean follow-up of 5.0 years. A total of 209 (49.3%) patients with
      EAC were in BE surveillance programme and were diagnosed as a result of
      surveillance endoscopy. These patients were more likely to be diagnosed at an
      early stage (stage 0 or 1: 74.7% vs 56.2, p<0.001), survived longer (median 3.2
      vs 2.3 years; p<0.001) and have lower cancer-related mortality (34.0% vs 54.0%,
      p<0.0001) and had a trend to receive oesophagectomy (51.2% vs 42.3%; p=0.07) than
      215 patients diagnosed by non-BE surveillance endoscopy (17.2% of whom were BE
      surveillance failure). BE surveillance endoscopy was associated with a decreased
      risk of cancer-related death (HR 0.47, 0.35 to 0.64), which was largely explained
      by the early stage of EAC at the time of diagnosis. Similarly, the adjusted
      mortality for patients with cancer in a prior surveillance programme for overall
      death was 0.63 (0.47 to 0.84) compared with patients with cancer not in a
      surveillance programme. CONCLUSIONS: Surveillance endoscopy among patients with
      BE is associated with significantly better EAC outcomes including cancer-related
      mortality compared with other non-surveillance endoscopy.

PMID- 26311718
TI  - Airborne Asbestos Exposures from Warm Air Heating Systems in Schools.
AB  - The aim of this study was to investigate the concentrations of airborne asbestos
      that can be released into classrooms of schools that have amosite-containing
      asbestos insulation board (AIB) in the ceiling plenum or other spaces,
      particularly where there is forced recirculation of air as part of a warm air
      heating system. Air samples were collected in three or more classrooms at each of
      three schools, two of which were of CLASP (Consortium of Local Authorities
      Special Programme) system-built design, during periods when the schools were
      unoccupied. Two conditions were sampled: (i) the start-up and running of the
      heating systems with no disturbance (the background) and (ii) running of the
      heating systems during simulated disturbance. The simulated disturbance was
      designed to exceed the level of disturbance to the AIB that would routinely take
      place in an occupied classroom. A total of 60 or more direct impacts that
      vibrated and/or flexed the encapsulated or enclosed AIB materials were applied
      over the sampling period. The impacts were carried out at the start of the
      sampling and repeated at hourly intervals but did not break or damage the AIB.
      The target air volume for background samples was ~3000 l of air using a static
      sampler sited either below or ~1 m from the heater outlet. This would allow an
      analytical sensitivity (AS) of 0.0001 fibres per millilitre (f ml(-1)) to be
      achieved, which is 1000 times lower than the EU and UK workplace control limit of
      0.1 f ml(-1). Samples with lower volumes of air were also collected in case of
      overloading and for the shorter disturbance sampling times used at one site. The
      sampler filters were analysed by phase contrast microscopy (PCM) to give a rapid
      determination of the overall concentration of visible fibres (all types) released
      and/or by analytical transmission electron microscopy (TEM) to determine the
      concentration of asbestos fibres. Due to the low number of fibres, results were
      reported in terms of both the calculated concentration and the statistically
      relevant limits of quantification (LOQ), which are routinely applied. The PCM
      fibre concentrations were all below the LOQ but analytical TEM showed that few of
      the fibres counted in the background samples were asbestos. The background TEM
      asbestos concentrations for the individual samples analysed from all three
      schools were at or below the AS, with a pooled average below the LOQ (<0.00005 f
      ml(-1)). At the two CLASP schools, there was no significant increase in the
      airborne amosite concentration in the classrooms during simulated disturbance
      conditions. At the third school, four of the five classrooms sampled gave
      measurable concentrations of amosite by TEM during simulated disturbance
      conditions. The highest concentration of amosite fibres countable by PCM was
      0.0043 f ml(-1) with a pooled average of 0.0019 f ml(-1). The air sampling
      strategy was effective and worked well and the results provide further important
      evidence to inform the sampling and management of asbestos in schools. 

PMID- 26311717
TI  - Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis.
AB  - OBJECTIVE: Accumulating evidence links the intestinal microbiota and colorectal
      carcinogenesis. Fusobacterium nucleatum may promote colorectal tumour growth and
      inhibit T cell-mediated immune responses against colorectal tumours. Thus, we
      hypothesised that the amount of F. nucleatum in colorectal carcinoma might be
      associated with worse clinical outcome. DESIGN: We used molecular pathological
      epidemiology database of 1069 rectal and colon cancer cases in the Nurses' Health
      Study and the Health Professionals Follow-up Study, and measured F. nucleatum DNA
      in carcinoma tissue. Cox proportional hazards model was used to compute hazard
      ratio (HR), controlling for potential confounders, including microsatellite
      instability (MSI, mismatch repair deficiency), CpG island methylator phenotype
      (CIMP), KRAS, BRAF, and PIK3CA mutations, and LINE-1 hypomethylation (low-level
      methylation). RESULTS: Compared with F. nucleatum-negative cases, multivariable
      HRs (95% CI) for colorectal cancer-specific mortality in F. nucleatum-low cases
      and F. nucleatum-high cases were 1.25 (0.82 to 1.92) and 1.58 (1.04 to 2.39),
      respectively, (p for trend=0.020). The amount of F. nucleatum was associated with
      MSI-high (multivariable odd ratio (OR), 5.22; 95% CI 2.86 to 9.55) independent of
      CIMP and BRAF mutation status, whereas CIMP and BRAF mutation were associated
      with F. nucleatum only in univariate analyses (p<0.001) but not in multivariate
      analysis that adjusted for MSI status. CONCLUSIONS: The amount of F. nucleatum
      DNA in colorectal cancer tissue is associated with shorter survival, and may
      potentially serve as a prognostic biomarker. Our data may have implications in
      developing cancer prevention and treatment strategies through targeting GI
      microflora by diet, probiotics and antibiotics.

PMID- 26311721
TI  - Impact of Glucose Meter Error on Glycemic Variability and Time in Target Range
      During Glycemic Control After Cardiovascular Surgery.
AB  - BACKGROUND: We retrospectively studied the impact of glucose meter error on the
      efficacy of glycemic control after cardiovascular surgery. METHOD: Adult patients
      undergoing intravenous insulin glycemic control therapy after cardiovascular
      surgery, with 12-24 consecutive glucose meter measurements used to make insulin
      dosing decisions, had glucose values analyzed to determine glycemic variability
      by both standard deviation (SD) and continuous overall net glycemic action
      (CONGA), and percentage glucose values in target glucose range (110-150 mg/dL).
      Information was recorded for 70 patients during each of 2 periods, with different
      glucose meters used to measure glucose and dose insulin during each period but no
      other changes to the glycemic control protocol. Accuracy and precision of each
      meter were also compared using whole blood specimens from ICU patients. RESULTS:
      Glucose meter 1 (GM1) had median bias of 11 mg/dL compared to a laboratory
      reference method, while glucose meter 2 (GM2) had a median bias of 1 mg/dL. GM1
      and GM2 differed little in precision (CV = 2.0% and 2.7%, respectively). Compared
      to the period when GM1 was used to make insulin dosing decisions, patients whose
      insulin dose was managed by GM2 demonstrated reduced glycemic variability as
      measured by both SD (13.7 vs 21.6 mg/dL, P < .0001) and CONGA (13.5 vs 19.4
      mg/dL, P < .0001) and increased percentage glucose values in target range (74.5
      vs 66.7%, P = .002). CONCLUSIONS: Decreasing glucose meter error (bias) was
      associated with decreased glycemic variability and increased percentage of values
      in target glucose range for patients placed on intravenous insulin therapy
      following cardiovascular surgery.

PMID- 26311720
TI  - Accuracy and Injection Force of the Gla-300 Injection Device Compared With Other
      Commercialized Disposable Insulin Pens.
AB  - BACKGROUND: To deliver insulin glargine 300 U/mL (Gla-300), the widely used
      SoloSTAR((r)) pen has been modified to allow for accurate and precise delivery of
      required insulin units in one-third of the volume compared with insulin glargine
      100 U/mL, while improving usability. Here we compare the accuracy and injection
      force of 3 disposable insulin pens: Gla-300 SoloSTAR((r)), FlexPen((r)), and
      KwikPenTM. METHODS: For the accuracy assessment, 60 of each of the 3 tested
      devices were used for the delivery of 3 different doses (1 U, half-maximal dose,
      and maximal dose), which were measured gravimetrically. For the injection force
      assessment, 20 pens of each of the 3 types were tested twice at half-maximal and
      once at maximal dose, at an injection speed of 6 U/s. RESULTS: All tested pens
      met the International Organization for Standardization (ISO) requirements for
      dosing accuracy, with Gla-300 SoloSTAR showing the lowest between-dose variation
      (greatest reproducibility) at all dose levels. Mean injection force was
      significantly lower for Gla-300 SoloSTAR than for the other 2 pens at both half
      maximal and maximal doses (P < .0271). CONCLUSION: All tested pens were accurate
      according to ISO criteria, and the Gla-300 SoloSTAR pen displayed the greatest
      reproducibility and lowest injection force of any of the 3 tested devices.

PMID- 26311722
TI  - Doctors face compulsory system to declare gifts and hospitality from drug
      companies.

PMID- 26311719
TI  - MicroRNA-143 Activation Regulates Smooth Muscle and Endothelial Cell Crosstalk in
      Pulmonary Arterial Hypertension.
AB  - RATIONALE: The pathogenesis of pulmonary arterial hypertension (PAH) remains
      unclear. The 4 microRNAs representing the miR-143 and miR-145 stem loops are
      genomically clustered. OBJECTIVE: To elucidate the transcriptional regulation of
      the miR-143/145 cluster and the role of miR-143 in PAH. METHODS AND RESULTS: We
      identified the promoter region that regulates miR-143/145 microRNA expression in
      pulmonary artery smooth muscle cells (PASMCs). We mapped PAH-related signaling
      pathways, including estrogen receptor, liver X factor/retinoic X receptor,
      transforming growth factor-beta (Smads), and hypoxia (hypoxia response element),
      that regulated levels of all pri-miR stem loop transcription and resulting
      microRNA expression. We observed that miR-143-3p is selectively upregulated
      compared with miR-143-5p during PASMC migration. Modulation of miR-143 in PASMCs
      significantly altered cell migration and apoptosis. In addition, we found high
      abundance of miR-143-3p in PASMC-derived exosomes. Using assays with pulmonary
      arterial endothelial cells, we demonstrated a paracrine promigratory and
      proangiogenic effect of miR-143-3p-enriched exosomes from PASMC. Quantitative
      polymerase chain reaction and in situ hybridization showed elevated expression of
      miR-143 in calf models of PAH and in samples from PAH patients. Moreover, in
      contrast to our previous findings that had not supported a therapeutic role in
      vivo, we now demonstrate a protective role of miR-143 in experimental pulmonary
      hypertension in vivo in miR-143-/- and anti-miR-143-3p-treated mice exposed to
      chronic hypoxia in both preventative and reversal settings. CONCLUSIONS: MiR-143
      3p modulated both cellular and exosome-mediated responses in pulmonary vascular
      cells, whereas inhibition of miR-143-3p blocked experimental pulmonary
      hypertension. Taken together, these findings confirm an important role for the
      miR-143/145 cluster in PAH pathobiology.

PMID- 26311723
TI  - Analysis of distribution and severity of inflammation in patients with
      osteoarthitis compared to rheumatoid arthritis by ICG-enhanced fluorescence
      optical imaging and musculoskeletal ultrasound: a pilot study.
AB  - BACKGROUND: In rheumatoid arthritis (RA), hand synovitis appears especially in
      wrist, metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. In
      hand osteoarthritis (OA), potential inflammatory changes are mainly present in
      PIP and distal interphalangeal (DIP) joints. Joint inflammation can be visualised
      by fluorescence optical imaging (FOI) and musculoskeletal ultrasound (US).
      OBJECTIVE: Comparison of the amount and distribution of inflammatory signs in
      wrist and finger joints of the clinically dominant hand in patients with OA and
      RA by FOI and gray-scale (GSUS) and power Doppler US (PDUS). METHODS: FOI and
      GSUS/PDUS were performed in 1.170 joints (wrists, MCP, PIP, DIP) in 90 patients
      (67 RA, 23 OA). Joint inflammation was graded by a semiquantitative score (0-3)
      for each imaging method. RESULTS: GSUS/PDUS showed wrist and MCP joints mostly
      affected in RA. DIP joints were graded higher in OA. In FOI, RA and OA featured
      inflammatory changes in the respective joint groups depending on the phase of
      fluorescence dye flooding. CONCLUSIONS: US and FOI detected inflammation in both
      RA and OA highlighting the inflammatory component in the course of OA. The
      different inflammatory patterns and various shapes of fluorescence enhancement in
      FOI may offer opportunities to distinguish and determine the inflammatory status
      in both diseases.

PMID- 26311724
TI  - Relation of Smoking With Total Mortality and Cardiovascular Events Among Patients
      With Diabetes Mellitus: A Meta-Analysis and Systematic Review.
AB  - BACKGROUND: The prevalence of smoking in diabetic patients remains high, and
      reliable quantification of the excess mortality and morbidity risks associated
      with smoking is important for diabetes management. We performed a systematic
      review and meta-analysis of prospective cohort studies to evaluate the relation
      of active smoking with risk of total mortality and cardiovascular events among
      diabetic patients. METHODS AND RESULTS: We searched Medline and Embase databases
      through May 2015, and multivariate-adjusted relative risks were pooled by using
      random-effects models. A total of 89 cohort studies were included. The pooled
      adjusted relative risk (95% confidence interval) associated with smoking was 1.55
      (1.46-1.64) for total mortality (48 studies with 1,132,700 participants and
      109,966 deaths), and 1.49 (1.29-1.71) for cardiovascular mortality (13 studies
      with 37,550 participants and 3163 deaths). The pooled relative risk (95%
      confidence interval) was 1.44 (1.34-1.54) for total cardiovascular disease (16
      studies), 1.51 (1.41-1.62) for coronary heart disease (21 studies), 1.54 (1.41
      1.69) for stroke (15 studies), 2.15 (1.62-2.85) for peripheral arterial disease
      (3 studies), and 1.43 (1.19-1.72) for heart failure (4 studies). In comparison
      with never smokers, former smokers were at a moderately elevated risk of total
      mortality (1.19; 1.11-1.28), cardiovascular mortality (1.15; 1.00-1.32),
      cardiovascular disease (1.09; 1.05-1.13), and coronary heart disease (1.14; 1.00
      1.30), but not for stroke (1.04; 0.87-1.23). CONCLUSIONS: Active smoking is
      associated with significantly increased risks of total mortality and
      cardiovascular events among diabetic patients, whereas smoking cessation is
      associated with reduced risks in comparison with current smoking. The findings
      provide strong evidence for the recommendation of quitting smoking among diabetic
      patients.

PMID- 26311725
TI  - A Phase II Trial of the Multitargeted Tyrosine Kinase Inhibitor Lenvatinib
      (E7080) in Advanced Medullary Thyroid Cancer.
AB  - PURPOSE: Positive results of phase I studies evaluating lenvatinib in solid
      tumors, including thyroid cancer, prompted a phase II trial in advanced medullary
      thyroid carcinoma (MTC). EXPERIMENTAL DESIGN: Fifty-nine patients with
      unresectable progressive MTC per Response Evaluation Criteria In Solid Tumors
      (RECIST) v1.0 within the prior 12 months received lenvatinib (24-mg daily, 28-day
      cycles) until disease progression, unmanageable toxicity, withdrawal, or death.
      Prior anti-VEGFR therapy was permitted. The primary endpoint was objective
      response rate (ORR) by RECIST v1.0 and independent imaging review. RESULTS:
      Lenvatinib ORR was 36% [95% confidence interval (CI), 24%-49%]; all partial
      responses. ORR was comparable between patients with (35%) or without (36%) prior
      anti-VEGFR therapy. Disease control rate (DCR) was 80% (95% CI, 67%-89%); 44% had
      stable disease. Among responders, median time to response (TTR) was 3.5 months
      (95% CI, 1.9-3.7). Median progression-free survival (PFS) was 9.0 months (95% CI,
      7.0-not evaluable). Common toxicity criteria grade 3/4 treatment-emergent adverse
      events included diarrhea (14%), hypertension (7%), decreased appetite (7%),
      fatigue, dysphagia, and increased alanine aminotransferase levels (5% each). Ret
      proto-oncogene status did not correlate with outcomes. Low baseline levels of
      angiopoietin-2, hepatocyte growth factor, and IL8 were associated with tumor
      reduction and prolonged PFS. High baseline levels of VEGF, soluble VEGFR3, and
      platelet-derived growth factor BB, and low baseline levels of soluble Tie-2, were
      associated with tumor reduction. CONCLUSIONS: Lenvatinib had a high ORR, high
      DCR, and a short TTR in patients with documented progressive MTC. Toxicities were
      managed with dose modifications and medications.

PMID- 26311726
TI  - Trauma research--a field without a home base.

PMID- 26311727
TI  - Does molecular monitoring matter in early-stage breast cancer?
AB  - Serial monitoring of circulating tumor DNA predicts recurrence after treatment
      for localized breast cancer (Garcia-Murillas et al., this issue). 

PMID- 26311728
TI  - Mutation tracking in circulating tumor DNA predicts relapse in early breast
      cancer.
AB  - The identification of early-stage breast cancer patients at high risk of relapse
      would allow tailoring of adjuvant therapy approaches. We assessed whether
      analysis of circulating tumor DNA (ctDNA) in plasma can be used to monitor for
      minimal residual disease (MRD) in breast cancer. In a prospective cohort of 55
      early breast cancer patients receiving neoadjuvant chemotherapy, detection of
      ctDNA in plasma after completion of apparently curative treatment-either at a
      single postsurgical time point or with serial follow-up plasma samples-predicted
      metastatic relapse with high accuracy [hazard ratio, 25.1 (confidence interval,
      4.08 to 130.5; log-rank P < 0.0001) or 12.0 (confidence interval, 3.36 to 43.07;
      log-rank P < 0.0001), respectively]. Mutation tracking in serial samples
      increased sensitivity for the prediction of relapse, with a median lead time of
      7.9 months over clinical relapse. We further demonstrated that targeted capture
      sequencing analysis of ctDNA could define the genetic events of MRD, and that MRD
      sequencing predicted the genetic events of the subsequent metastatic relapse more
      accurately than sequencing of the primary cancer. Mutation tracking can therefore
      identify early breast cancer patients at high risk of relapse. Subsequent
      adjuvant therapeutic interventions could be tailored to the genetic events
      present in the MRD, a therapeutic approach that could in part combat the
      challenge posed by intratumor genetic heterogeneity. 

PMID- 26311729
TI  - Pronounced species divergence in corticospinal tract reorganization and
      functional recovery after lateralized spinal cord injury favors primates.
AB  - Experimental and clinical studies suggest that primate species exhibit greater
      recovery after lateralized compared to symmetrical spinal cord injuries. Although
      this observation has major implications for designing clinical trials and
      translational therapies, advantages in recovery of nonhuman primates over other
      species have not been shown statistically to date, nor have the associated repair
      mechanisms been identified. We monitored recovery in more than 400 quadriplegic
      patients and found that functional gains increased with the laterality of spinal
      cord damage. Electrophysiological analyses suggested that corticospinal tract
      reorganization contributes to the greater recovery after lateralized compared
      with symmetrical injuries. To investigate underlying mechanisms, we modeled
      lateralized injuries in rats and monkeys using a lateral hemisection, and
      compared anatomical and functional outcomes with patients who suffered similar
      lesions. Standardized assessments revealed that monkeys and humans showed greater
      recovery of locomotion and hand function than did rats. Recovery correlated with
      the formation of corticospinal detour circuits below the injury, which were
      extensive in monkeys but nearly absent in rats. Our results uncover pronounced
      interspecies differences in the nature and extent of spinal cord repair
      mechanisms, likely resulting from fundamental differences in the anatomical and
      functional characteristics of the motor systems in primates versus rodents.
      Although rodents remain essential for advancing regenerative therapies, the
      unique response of the primate corticospinal tract after injury reemphasizes the
      importance of primate models for designing clinically relevant treatments. 

PMID- 26311730
TI  - IgH sequences in common variable immune deficiency reveal altered B cell
      development and selection.
AB  - Common variable immune deficiency (CVID) is the most common symptomatic primary
      immune deficiency, affecting ~1 in 25,000 persons. These patients suffer from
      impaired antibody responses, autoimmunity, and susceptibility to lymphoid
      cancers. To explore the cellular basis for these clinical phenotypes, we
      conducted high-throughput DNA sequencing of immunoglobulin heavy chain gene
      rearrangements from 93 CVID patients and 105 control subjects and sorted naive
      and memory B cells from 13 of the CVID patients and 10 of the control subjects.
      The CVID patients showed abnormal VDJ rearrangement and abnormal formation of
      complementarity-determining region 3 (CDR3). We observed a decreased selection
      against antibodies with long CDR3s in memory repertoires and decreased variable
      gene replacement, offering possible mechanisms for increased patient
      autoreactivity. Our data indicate that patient immunodeficiency might derive from
      both decreased diversity of the naive B cell pool and decreased somatic
      hypermutation in memory repertoires. The CVID patients also exhibited an abnormal
      clonal expansion of unmutated B cells relative to the controls. Although impaired
      B cell germinal center activation is commonly viewed as causative in CVID, these
      data indicate that CVID B cells diverge from controls as early as the pro-B
      stage, cell and suggest possible explanations for the increased incidence of
      autoimmunity, immunodeficiency, and lymphoma CVID patients. 

PMID- 26311731
TI  - A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary
      neuroendocrine tumor-initiating cells in vivo.
AB  - The high-grade pulmonary neuroendocrine tumors, small cell lung cancer (SCLC) and
      large cell neuroendocrine carcinoma (LCNEC), remain among the most deadly
      malignancies. Therapies that effectively target and kill tumor-initiating cells
      (TICs) in these cancers should translate to improved patient survival. Patient
      derived xenograft (PDX) tumors serve as excellent models to study tumor biology
      and characterize TICs. Increased expression of delta-like 3 (DLL3) was discovered
      in SCLC and LCNEC PDX tumors and confirmed in primary SCLC and LCNEC tumors. DLL3
      protein is expressed on the surface of tumor cells but not in normal adult
      tissues. A DLL3-targeted antibody-drug conjugate (ADC), SC16LD6.5, comprised of a
      humanized anti-DLL3 monoclonal antibody conjugated to a DNA-damaging
      pyrrolobenzodiazepine (PBD) dimer toxin, induced durable tumor regression in vivo
      across multiple PDX models. Serial transplantation experiments executed with
      limiting dilutions of cells provided functional evidence confirming that the lack
      of tumor recurrence after SC16LD6.5 exposure resulted from effective targeting of
      DLL3-expressing TICs. In vivo efficacy correlated with DLL3 expression, and
      responses were observed in PDX models initiated from patients with both limited
      and extensive-stage disease and were independent of their sensitivity to standard
      of-care chemotherapy regimens. SC16LD6.5 effectively targets and eradicates DLL3
      expressing TICs in SCLC and LCNEC PDX tumors and is a promising first-in-class
      ADC for the treatment of high-grade pulmonary neuroendocrine tumors. 

PMID- 26311732
TI  - Genetic consequences of cladogenetic vs. anagenetic speciation in endemic plants
      of oceanic islands.
AB  - Adaptive radiation is a common mode of speciation among plants endemic to oceanic
      islands. This pattern is one of cladogenesis, or splitting of the founder
      population, into diverse lineages in divergent habitats. In contrast, endemic
      species have also evolved primarily by simple transformations from progenitors in
      source regions. This is anagenesis, whereby the founding population changes
      genetically and morphologically over time primarily through mutation and
      recombination. Gene flow among populations is maintained in a homogeneous
      environment with no splitting events. Genetic consequences of these modes of
      speciation have been examined in the Juan Fernandez Archipelago, which contains
      two principal islands of differing geological ages. This article summarizes
      population genetic results (nearly 4000 analyses) from examination of 15 endemic
      species, involving 1716 and 1870 individuals in 162 and 163 populations (with
      amplified fragment length polymorphisms and simple sequence repeats,
      respectively) in the following genera: Drimys (Winteraceae), Myrceugenia
      (Myrtaceae), Rhaphithamnus (Verbenaceae), Robinsonia (Asteraceae, Senecioneae)
      and Erigeron (Asteraceae, Astereae). The results indicate that species
      originating anagenetically show high levels of genetic variation within the
      island population and no geographic genetic partitioning. This contrasts with
      cladogenetic species that show less genetic diversity within and among
      populations. Species that have been derived anagenetically on the younger island
      (1-2 Ma) contain less genetic variation than those that have anagenetically
      speciated on the older island (4 Ma). Genetic distinctness among cladogenetically
      derived species on the older island is greater than among similarly derived
      species on the younger island. An important point is that the total genetic
      variation within each genus analysed is comparable, regardless of whether
      adaptive divergence occurs. 

PMID- 26311733
TI  - Long-term ecology resolves the timing, region of origin and process of
      establishment for a disputed alien tree.
AB  - Alien plants are a pervasive environmental problem, particularly on islands where
      they can rapidly transform unique indigenous ecosystems. However, often it is
      difficult to confidently determine whether a species is native or alien,
      especially if establishment occurred before historical records. This can present
      a management challenge: for example, should such taxa be eradicated or left alone
      until their region of origin and status are clarified? Here we show how combining
      palaeoecological and historical records can help resolve such dilemmas, using the
      tree daisy Olearia lyallii on the remote New Zealand subantarctic Auckland
      Islands as a case study. The status of this tree as native or introduced has
      remained uncertain for the 175 years since it was first discovered on the
      Auckland Islands, and its appropriate management is debated. Elsewhere, O.
      lyallii has a highly restricted distribution on small sea bird-rich islands
      within a 2 degrees  latitudinal band south of mainland New Zealand. Analysis of
      palaeoecological and historical records from the Auckland Islands suggest that O.
      lyallii established there c. 1807 when these islands were first exploited by
      European sealers. Establishment was facilitated by anthropogenic burning and
      clearing and its subsequent spread has been slow, limited in distribution and
      probably human-assisted. Olearia lyallii has succeeded mostly in highly disturbed
      sites which are also nutrient enriched from nesting sea birds, seals and sea
      spray. This marine subsidy has fuelled the rapid growth of O. lyallii and allowed
      this tree to be competitive against the maritime communities it has replaced.
      Although endemic to the New Zealand region, our evidence suggests that O. lyallii
      is alien to the Auckland Islands. Although such 'native' aliens can pose unique
      management challenges on islands, in this instance we suggest that ongoing
      monitoring with no control is an appropriate management action, as O. lyallii
      appears to pose minimal risk to ecological integrity. 

PMID- 26311734
TI  - Diversity and population structure of a dominant deciduous tree based on
      morphological and genetic data.
AB  - Knowledge of the genetic diversity and structure of tree species across their
      geographic ranges is essential for sustainable use and management of forest
      ecosystems. Acer grosseri Pax., an economically and ecologically important maple
      species, is mainly distributed in North China. In this study, the genetic
      diversity and population differentiation of 24 natural populations of this
      species were evaluated using sequence-related amplified polymorphism markers and
      morphological characters. The results show that highly significant differences
      occurred in 32 morphological traits. The coefficient of variation of 34
      characters was 18.19 %. Principal component analysis indicated that 18 of 34
      traits explained 60.20 % of the total variance. The phenotypic differentiation
      coefficient (VST) was 36.06 % for all morphological traits. The Shannon-Wiener
      index of 34 morphological characters was 6.09, while at the population level, it
      was 1.77. The percentage of polymorphic bands of all studied A. grosseri
      populations was 82.14 %. Nei's gene diversity (He) and Shannon's information
      index (I) were 0.35 and 0.50, respectively. Less genetic differentiation was
      detected among the natural populations (GST = 0.20, PhiST = 0.10). Twenty-four
      populations of A. grosseri formed two main clusters, which is consistent with
      morphological cluster analysis. Principal coordinates analysis and STRUCTURE
      analysis supported the UPGMA-cluster dendrogram. There was no significant
      correlation between genetic and geographical distances among populations. Both
      molecular and morphological data suggested that A. grosseri is rich in genetic
      diversity. The high level of genetic variation within populations could be
      affected by the biological characters, mating system and lifespan of A. grosseri,
      whereas the lower genetic diversity among populations could be caused by
      effective gene exchange, selective pressure from environmental heterogeneity and
      the species' geographical range. 

PMID- 26311735
TI  - Managing Loss and Change: Grief Interventions for Dementia Caregivers in a CBT
      Based Trial.
AB  - Dementia caregivers often experience loss and grief related to general caregiver
      burden, physical, and mental health problems. Through qualitative content
      analysis, this study analyzed intervention strategies applied by therapists in a
      randomized-controlled trial in Germany to assist caregivers in managing losses
      and associated emotions. Sequences from 61 therapy sessions that included
      interventions targeting grief, loss, and change were transcribed and analyzed. A
      category system was developed deductively, and the intercoder reliability was
      satisfactory. The identified grief intervention strategies were recognition and
      acceptance of loss and change,addressing future losses,normalization of grief,
      and redefinition of the relationship Therapists focused on identifying
      experienced losses, managing associated feelings, and fostering acceptance of
      these losses. A variety of cognitive-behavioral therapy-based techniques was
      applied with each strategy. The findings contribute to understanding how dementia
      caregivers can be supported in their experience of grief and facilitate the
      development of a manualized grief intervention.

PMID- 26311736
TI  - Dog-appeasing pheromone collars reduce sound-induced fear and anxiety in beagle
      dogs: a placebo-controlled study.
AB  - The objective of the study was to assess the effects of a dog-appeasing pheromone
      (DAP) collar in reducing sound-induced fear and anxiety in a laboratory model of
      thunderstorm simulation. Twenty-four beagle dogs naive to the current test were
      divided into two treatment groups (DAP and placebo) balanced on their fear score
      in response to a thunderstorm recording. Each group was then exposed to two
      additional thunderstorm simulation tests on consecutive days. Dogs were video
      assessed by a trained observer on a 6-point scale for active, passive and global
      fear and anxiety (combined). Both global and active fear and anxiety scores were
      significantly improved during and following thunder compared with placebo on both
      test days. DAP significantly decreased global fear and anxiety across 'during'
      and 'post' thunder times when compared with baseline. There was no significant
      improvement in the placebo group from baseline on the test days. In addition, the
      DAP group showed significantly greater use of the hide box at any time with
      increased exposure compared with the placebo group. The DAP collar reduced the
      scores of fear and anxiety, and increased hide use in response to a thunder
      recording, possibly by counteracting noise-related increased reactivity. 

PMID- 26311737
TI  - Licochalcone A induces autophagy through PI3K/Akt/mTOR inactivation and autophagy
      suppression enhances Licochalcone A-induced apoptosis of human cervical cancer
      cells.
AB  - The use of dietary bioactive compounds in chemoprevention can potentially
      reverse, suppress, or even prevent cancer progression. However, the effects of
      licochalcone A (LicA) on apoptosis and autophagy in cervical cancer cells have
      not yet been clearly elucidated. In this study, LicA treatment was found to
      significantly induce the apoptotic and autophagic capacities of cervical cancer
      cells in vitro and in vivo. MTT assay results showed dose- and time-dependent
      cytotoxicity in four cervical cancer cell lines treated with LicA. We found that
      LicA induced mitochondria-dependent apoptosis in SiHa cells, with decreasing Bcl
      2 expression. LicA also induced autophagy effects were examined by identifying
      accumulation of Atg5, Atg7, Atg12 and microtubule-associated protein 1 light
      chain 3 (LC3)-II. Treatment with autophagy-specific inhibitors (3-methyladenine
      and bafilomycin A1) enhanced LicA-induced apoptosis. In addition, we suggested
      the inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of
      mTOR pathway by LicA. Furthermore, the inhibition of PI3K/Akt by LY294002/si-Akt
      or of mTOR by rapamycin augmented LicA-induced apoptosis and autophagy. Finally,
      the in vivo mice bearing a SiHa xenograft, LicA dosed at 10 or 20 mg/kg
      significantly inhibited tumor growth. Our findings demonstrate the
      chemotherapeutic potential of LicA for treatment of human cervical cancer. 

PMID- 26311738
TI  - A novel pathogenic germline mutation in the adenomatous polyposis coli gene in a
      Chinese family with familial adenomatous coli.
AB  - Familial adenomatous polyposis (FAP) is an autosomal dominant disease manifesting
      as colorectal cancer in middle-aged patients. Mutations of the adenomatous
      polyposis coli (APC) gene contribute to both FAP and sporadic or familial
      colorectal carcinogenesis. Here we describe the identification of the causative
      APC gene defects associated with FAP in a Chinese pedigree. All patients with FAP
      were diagnosed by their combination of clinical features, family history,
      colonoscopy, and pathology examinations. Blood samples were collected and genomic
      DNA was extracted. Mutation analysis of APC was conducted by targeted next
      generation sequencing, long-range PCR and Sanger sequencing. A novel mutation in
      exon 14-15(c.1936-2148 del) and intron 14 of the APC gene was demonstrated in all
      FAP patients and was absent in unaffected family members. This novel deletion
      causing FAP in Chinese kindred expands the germline mutation spectrum of the APC
      gene in the Chinese population. 

PMID- 26311739
TI  - Phase II study of docetaxel, cisplatin, and fluorouracil in patients with
      distantly metastatic penile cancer as first-line chemotherapy.
AB  - PURPOSE: Patients with distantly metastatic (M1) penile squamous carcinoma have
      extremely poor prognosis and few prospective clinical trials evaluating systemic
      treatment have ever been performed for this population. METHODS: Patients (aged
      >= 18 years) with histologically confirmed, distantly metastatic, measurable
      penile squamous carcinoma were enrolled. They were treated with docetaxel 75
      mg/m2 (day1), cisplatin 70 mg/m2 (day1), and fluorouracil 500 mg/m2/d (days 1 to
      5) every 3 weeks as first line chemotherapy. The primary endpoint was objective
      response rate (ORR). RESULTS: 39 patients received chemotherapy with a median of
      four cycles (range two to six). The median follow-up time was 11 months. 15
      patients had a confirmed objective response (38.5%, 95% CI 23.36-55.38), all of
      which were partial responses. The median progression-free survival (PFS) was 3
      months (95% CI 2.92-3.09), and the median overall survival (OS) was 7 months (95%
      CI 5.99-8.03). Toxicity was manageable and the most frequently recorded adverse
      events of grade 3 or higher were neutropenia (13 of 39; 33%), nausea/vomiting (7
      of 39;18%). There was no treatment-related death. CONCLUSION: The palliative
      regimen of docetaxel, fluorouracil, and cisplatin induced moderate responses and
      can be used as a choice for the treatment of patients with distantly metastatic
      penile cancer. However, efforts to improve efficacy and minimize toxicity for
      this regimen should be made in the future.

PMID- 26311740
TI  - MiR-21 mediates sorafenib resistance of hepatocellular carcinoma cells by
      inhibiting autophagy via the PTEN/Akt pathway.
AB  - Sorafenib resistance remains a major obstacle for the effective treatments of
      hepatocellular carcinoma (HCC). Recent studies indicate that activated Akt
      contributes to the acquired resistance to sorafenib, and miR-21 dysregulates
      phosphatase and tensin homolog (PTEN), which inhibits Akt activation. Sorafenib
      resistant HCC cells were shown to be refractory to sorafenib-induced growth
      inhibition and apoptosis. Akt and its downstream factors were highly activated
      and/or upregulated in sorafenib-resistant cells. Inhibition of autophagy
      decreased the sensitivity of sorafenib-resistant cells to sorafenib, while its
      induction had the opposite effect. Differential screening of miRNAs showed higher
      levels of miR-21 in sorafenib-resistant HCC cells. Exposure of HCC cells to
      sorafenib led to an increase in miR-21 expression, a decrease in PTEN expression
      and sequential Akt activation. Transfection of miR-21 mimics in HCC cells
      restored sorafenib resistance by inhibiting autophagy. Anti-miR-21
      oligonucleotides re-sensitized sorafenib-resistant cells by promoting autophagy.
      Inhibition of miR-21 enhances the efficacy of sorafenib in treating sorafenib
      resistant HCC tumors in vivo. We conclude that miR-21 participates in the
      acquired resistance of sorafenib by suppresing autophagy through the Akt/PTEN
      pathway. MiR-21 could serve as a therapeutic target for overcoming sorafenib
      resistance in the treatment of HCC. 

PMID- 26311741
TI  - Sphingosine kinase 1 is a reliable prognostic factor and a novel therapeutic
      target for uterine cervical cancer.
AB  - Sphingosine kinase 1 (SPHK1), an oncogenic kinase, has previously been found to
      be upregulated in various types of human malignancy and to play a crucial role in
      tumor development and progression. Although SPHK1 has gained increasing
      prominence as an important enzyme in cancer biology, its potential as a
      predictive biomarker and a therapeutic target in cervical cancer remains unknown.
      SPHK1 expression was examined in 287 formalin-fixed, paraffin-embedded cervical
      cancer tissues using immunohistochemistry, and its clinical implications and
      prognostic significance were analyzed. Cervical cancer cell lines including HeLa
      and SiHa were treated with the SPHK inhibitors SKI-II or FTY720, and effects on
      cell survival, apoptosis, angiogenesis, and invasion were examined. Moreover, the
      effects of FTY720 on tumor growth were evaluated using a patient-derived
      xenograft (PDX) model of cervical cancer. Immunohistochemical analysis revealed
      that expression of SPHK1 was significantly increased in cervical cancer compared
      with normal tissues. SPHK1 expression was significantly associated with tumor
      size, invasion depth, FIGO stage, lymph node metastasis, and lymphovascular
      invasion. Patients with high SPHK1 expression had lower overall survival and
      recurrence-free survival rates than those with low expression. Treatment with
      SPHK inhibitors significantly reduced viability and increased apoptosis in
      cervical cancer cells. Furthermore, FTY720 significantly decreased in vivo tumor
      weight in the PDX model of cervical cancer. We provide the first convincing
      evidence that SPHK1 is involved in tumor development and progression of cervical
      cancer. Our data suggest that SPHK1 might be a potential prognostic marker and
      therapeutic target for the treatment of cervical cancer. 

PMID- 26311742
TI  - Diabetes and Abdominal Aortic Aneurysm Growth.
AB  - We performed a systematic literature search and a meta-analysis to assess the
      association between diabetes mellitus (DM) and abdominal aortic aneurysm (AAA)
      growth. Databases including MEDLINE and EMBASE were searched through June 2015
      using PubMed and OVID. For each study, data regarding AAA growth rates in both
      the DM and the non-DM groups were used to generate standardized mean differences
      (SMDs) and 95% confidence intervals (CIs). Our search identified 19 relevant
      studies including data on 9777 patients with AAA. Pooled analyses demonstrated a
      statistically significant slower growth rates in DM patients than in non-DM
      patients (unadjusted SMD, -0.32; 95% CI, -0.40 to -0.24; P < .00001; adjusted
      SMD, -0.29; 95% CI, -0.417 to -0.18; P < .00001). Despite possible publication
      bias in favor of DM based on funnel plot asymmetry, even adjustment of the
      asymmetry did not alter the beneficial effect of DM. In conclusion, on the basis
      of a meta-analysis of data on a total of 9777 patients (19 studies) identified
      through a systematic literature search, we confirmed the association of DM with
      slower growth rates of AAA.

PMID- 26311744
TI  - Can big data help us close an epilepsy care gap?

PMID- 26311743
TI  - Identification of the DEAD box RNA helicase DDX3 as a therapeutic target in
      colorectal cancer.
AB  - Identifying druggable targets in the Wnt-signaling pathway can optimize
      colorectal cancer treatment. Recent studies have identified a member of the RNA
      helicase family DDX3 (DDX3X) as a multilevel activator of Wnt signaling in cells
      without activating mutations in the Wnt-signaling pathway. In this study, we
      evaluated whether DDX3 plays a role in the constitutively active Wnt pathway that
      drives colorectal cancer. We determined DDX3 expression levels in 303 colorectal
      cancers by immunohistochemistry. 39% of tumors overexpressed DDX3. High
      cytoplasmic DDX3 expression correlated with nuclear beta-catenin expression, a
      marker of activated Wnt signaling. Functionally, we validated this finding in
      vitro and found that inhibition of DDX3 with siRNA resulted in reduced TCF4
      reporter activity and lowered the mRNA expression levels of downstream TCF4
      regulated genes. In addition, DDX3 knockdown in colorectal cancer cell lines
      reduced proliferation and caused a G1 arrest, supporting a potential oncogenic
      role of DDX3 in colorectal cancer. RK-33 is a small molecule inhibitor designed
      to bind to the ATP-binding site of DDX3. Treatment of colorectal cancer cell
      lines and patient-derived 3D cultures with RK-33 inhibited growth and promoted
      cell death with IC50 values ranging from 2.5 to 8 MUM. The highest RK-33
      sensitivity was observed in tumors with wild-type APC-status and a mutation in
      CTNNB1. Based on these results, we conclude that DDX3 has an oncogenic role in
      colorectal cancer. Inhibition of DDX3 with the small molecule inhibitor RK-33
      causes inhibition of Wnt signaling and may therefore be a promising future
      treatment strategy for a subset of colorectal cancers. 

PMID- 26311745
TI  - Greater motor progression in patients with Parkinson disease who carry LRRK2 risk
      variants.
AB  - OBJECTIVES: In a longitudinal follow-up study, we compared the clinical features
      and motor progression of patients with Parkinson disease (PD) who are carriers of
      the leucine-rich repeat kinase 2 (LRRK2) gene risk variants with patients who are
      noncarriers. METHODS: We prospectively evaluated a cohort of patients with PD for
      their clinical characteristics, disease severity, and LRRK2 genotype. Carriers of
      risk variants (G2385R, R1628P, S1647T) and noncarriers were classified
      separately. A longitudinal, linear mixed model analysis of motor score
      progression was performed to compare motor progression between the 2 groups.
      Motor score progression was defined as the difference between Unified Parkinson's
      Disease Rating Scale motor score at baseline and follow-up scores. RESULTS: A
      total of 184 patients (122 risk variant carriers and 62 noncarriers) were
      evaluated and followed up for up to 6.5 years. No differences in demographics and
      baseline disease characteristics were found. In the longitudinal, linear mixed
      model analysis, risk variant carriers experienced greater rate of motor
      progression than noncarriers after 4 years from the date of diagnosis (p <=
      0.018). CONCLUSIONS: PD LRRK2 risk variant carriers showed greater motor
      progression after 4 years of disease duration compared with noncarrier patients,
      suggesting that these risk variants may facilitate neurodegeneration with
      increasing disease duration.

PMID- 26311747
TI  - Recurrent stroke in childhood cancer survivors.
AB  - OBJECTIVE: To estimate the rates and predictors of recurrent stroke among
      survivors of pediatric cancer who have had a first stroke. METHODS: The Childhood
      Cancer Survivor Study is a retrospective cohort study with longitudinal follow-up
      that enrolled 14,358 survivors (<21 years old at diagnosis; diagnosed 1970-1986;
      survived >=5 years after cancer diagnosis) and followed them prospectively since
      1994. We surveyed 443 survivors who reported a first stroke to identify recurrent
      stroke, and estimated recurrent stroke rates >=5 years after cancer diagnosis.
      RESULTS: Among 329 respondents (74% response rate), 271 confirmed a first stroke
      at a median age of 19 years (range 0-53), and 70 reported a second stroke at a
      median age of 32 years (range 1-56). In a multivariable Cox proportional hazards
      model, independent predictors of recurrent stroke included cranial radiation
      therapy (CRT) dose of >=50 Gy (vs none, hazard ratio [HR] 4.4; 95% confidence
      interval [CI] 1.4-13.7), hypertension (HR 1.9; 95% CI 1.0-3.5), and older age at
      first stroke (HR 6.4; 95% CI 1.8-23; for age >=40 vs age 0-17 years). The 10-year
      cumulative incidence of late recurrent stroke was 21% (95% CI 16%-27%) overall,
      and 33% (95% CI 21%-44%) for those treated with >=50 Gy of CRT. CONCLUSION:
      Survivors of childhood cancer, particularly those previously treated with high
      dose cranial radiation, have a high risk of recurrent stroke for decades after a
      first stroke. Although these strokes are mostly occurring in young adulthood,
      hypertension, an established atherosclerotic risk factor, independently predicts
      recurrent stroke in this population.

PMID- 26311746
TI  - Temporal course and pathologic basis of unawareness of memory loss in dementia.
AB  - OBJECTIVE: To characterize the natural history and neuropathologic basis of
      unawareness of memory loss in late-life dementia. METHODS: Analyses are based on
      2,092 older persons from 3 longitudinal clinical-pathologic cohort studies who
      had no memory or cognitive impairment at baseline. Annual evaluations included
      clinical classification of dementia plus self-rating and performance testing of
      memory. At death, there was a uniform neuropathologic examination to quantify 7
      dementia-related pathologies. RESULTS: In the full group, memory ratings were
      modestly correlated with memory performance (intercepts r = 0.26, p < 0.001;
      slopes r = 0.23, p < 001) and so we regressed each person's memory performance on
      their memory ratings, and the residuals provided longitudinal indicators of
      memory awareness. In a subset of 239 persons who developed dementia, episodic
      memory awareness was stable until a mean of 2.6 years before dementia onset (95%
      credible interval -2.7, -1.6); thereafter, memory awareness declined rapidly
      (mean annual change -0.32, 95% credible interval -0.37, -0.28). Older age at
      baseline was associated with later onset of memory unawareness. In a subset of
      385 persons who died and underwent neuropathologic examination, transactive
      response DNA-binding protein 43 (TDP-43) pathology, tau tangles, and gross
      cerebral infarcts were related to decline in memory awareness. In the absence of
      these pathologies, no decline in memory awareness was evident. Results were
      similar in subgroups with and without dementia. CONCLUSIONS: Awareness of memory
      impairment typically begins to decline about 2-3 years before dementia onset and
      is associated with postmortem evidence of TDP-43 pathology, tangles, and gross
      cerebral infarcts.

PMID- 26311749
TI  - Iron chelation therapy to prevent the manifestations of aceruloplasminemia.

PMID- 26311748
TI  - Association of Lp-PLA2-A and early recurrence of vascular events after TIA and
      minor stroke.
AB  - OBJECTIVE: To determine the association of lipoprotein-associated phospholipase
      A2 (Lp-PLA2) measured in the acute period and the short-term risk of recurrent
      vascular events in patients with TIA or minor stroke. METHODS: We measured Lp
      PLA2 activity (Lp-PLA2-A) in a subset of 3,201 participants enrolled in the
      CHANCE (Clopidogrel in High-Risk Patients with Acute Non-disabling
      Cerebrovascular Events) trial. Participants with TIA or minor stroke were
      enrolled within 24 hours of symptom onset and randomized to single or dual
      antiplatelet therapy. In the current analysis, the primary outcome was defined as
      the composite of ischemic stroke, myocardial infarction, or death within 90 days.
      RESULTS: The composite endpoint occurred in 299 of 3,021 participants (9.9%). The
      population average Lp-PLA2-A level was 209 +/- 59 nmol/min/mL (95% confidence
      interval [CI] 207-211). Older age, male sex, and current smoking were associated
      with higher Lp-PLA2-A levels. Lp-PLA2-A was significantly associated with the
      primary endpoint (adjusted hazard ratio 1.07, 95% CI 1.01-1.13 for every 30
      nmol/min/mL increase). Similar results were seen for ischemic stroke alone.
      Adjustment for low-density lipoprotein cholesterol attenuated the association
      between Lp-PLA2-A and the primary endpoint (adjusted hazard ratio 1.04, 95% CI
      0.97-1.11 for every 30 nmol/min/mL increase). CONCLUSIONS: Higher levels of Lp
      PLA2-A in the acute period are associated with increased short-term risk of
      recurrent vascular events.

PMID- 26311750
TI  - Prednisone/prednisolone and deflazacort regimens in the CINRG Duchenne Natural
      History Study.
AB  - OBJECTIVE: We aimed to perform an observational study of age at loss of
      independent ambulation (LoA) and side-effect profiles associated with different
      glucocorticoid corticosteroid (GC) regimens in Duchenne muscular dystrophy (DMD).
      METHODS: We studied 340 participants in the Cooperative International
      Neuromuscular Research Group Duchenne Natural History Study (CINRG-DNHS). LoA was
      defined as continuous wheelchair use. Effects of prednisone or prednisolone
      (PRED)/deflazacort (DFZ), administration frequency, and dose were analyzed by
      time-varying Cox regression. Side-effect frequencies were compared using chi(2)
      test. RESULTS: Participants treated >=1 year while ambulatory (n = 252/340)
      showed a 3-year median delay in LoA (p < 0.001). Fourteen different regimens were
      observed. Nondaily treatment was common for PRED (37%) and rare for DFZ (3%). DFZ
      was associated with later LoA than PRED (hazard ratio 0.294 +/- 0.053 vs 0.490 +/
      0.08, p = 0.003; 2-year difference in median LoA with daily administration, p <
      0.001). Average dose was lower for daily PRED (0.56 mg/kg/d, 75% of recommended)
      than daily DFZ (0.75 mg/kg/d, 83% of recommended, p < 0.001). DFZ showed higher
      frequencies of growth delay (p < 0.001), cushingoid appearance (p = 0.002), and
      cataracts (p < 0.001), but not weight gain. CONCLUSIONS: Use of DFZ was
      associated with later LoA and increased frequency of side effects. Differences in
      standards of care and dosing complicate interpretation of this finding, but
      stratification by PRED/DFZ might be considered in clinical trials. This study
      emphasizes the necessity of a randomized, blinded trial of GC regimens in DMD.
      CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that GCs are
      effective in delaying LoA in patients with DMD.

PMID- 26311752
TI  - Predicting frequent ED use by people with epilepsy with health information
      exchange data.
AB  - OBJECTIVES: To describe (1) the predictability of frequent emergency department
      (ED) use (a marker of inadequate disease control and/or poor access to care), and
      (2) the demographics, comorbidities, and use of health services of frequent ED
      users, among people with epilepsy. METHODS: We obtained demographics,
      comorbidities, and 2 years of encounter data for 8,041 people with epilepsy from
      a health information exchange in New York City. Using a retrospective cohort
      design, we explored bivariate relationships between baseline characteristics
      (year 1) and subsequent frequent ED use (year 2). We then built, evaluated, and
      compared predictive models to identify frequent ED users (>=4 visits year 2),
      using multiple techniques (logistic regression, lasso, elastic net, CART
      [classification and regression trees], Random Forests, AdaBoost, support vector
      machines). We selected a final model based on performance and simplicity.
      RESULTS: People with epilepsy who, in year 1, were adults (rather than children
      or seniors), male, Manhattan residents, frequent users of health services, users
      of multiple health systems, or had medical, neurologic, or psychiatric
      comorbidities, were more likely to frequently use the ED in year 2. Predictive
      techniques identified frequent ED visitors with good positive predictive value
      (approximately 70%) but poor sensitivity (approximately 20%). A simple strategy,
      selecting individuals with 11+ ED visits in year 1, performed as well as more
      sophisticated models. CONCLUSIONS: People with epilepsy with 11+ ED visits in a
      year are at highest risk of continued frequent ED use and may benefit from
      targeted intervention to avoid preventable ED visits. Future work should focus on
      improving the sensitivity of predictions.

PMID- 26311753
TI  - Eradication and elimination: facing the challenges, tempering expectations.

PMID- 26311754
TI  - Political, social and technical risks in the last stages of disease eradication
      campaigns.
AB  - Eradication of a disease is one of the greatest gifts any generation can give to
      subsequent ones, but most attempts have failed. The biggest challenges occur in
      the final stages of eradication and elimination campaigns. These include falling
      public support as a disease becomes less common; the emergence of groups who do
      not support eradication; spiralling costs; and the evolution of drug, vaccine or
      insecticide resistance. Mass campaigns become less effective as the disease
      fragments and modelling becomes less reliable. Optimism bias is the biggest risk
      to any eradication campaign and the long endgame must be planned for from the
      beginning. 

PMID- 26311755
TI  - From 'control to elimination': a strategic change to win the end game.
AB  - Strategies for elimination evolve from early use of available tools, to
      elaboration of control strategies, through to 'elimination.' Onchocerciasis
      control in Africa demonstrates this evolution. Early strategies used vector
      control but later used mass distribution of ivermectin. Elimination in Africa
      though was not thought to be possible; however, with excellent coverage of
      ivermectin distribution it was demonstrated that treatment could be stopped on
      the Senegal Mali border stimulating a new policy of elimination of transmission
      where possible. This new policy must not be business as usual but will require
      redefining treatment areas, improving quality of data, and flexibility of
      strategies to fit the new paradigm. 

PMID- 26311751
TI  - Long-term outcomes of generalized tonic-clonic seizures in a childhood absence
      epilepsy trial.
AB  - OBJECTIVE: To determine incidence and early predictors of generalized tonic
      clonic seizures (GTCs) in children with childhood absence epilepsy (CAE).
      METHODS: Occurrence of GTCs was determined in 446 children with CAE who
      participated in a randomized clinical trial comparing ethosuximide, lamotrigine,
      and valproate as initial therapy for CAE. RESULTS: As of June 2014, the cohort
      had been followed for a median of 7.0 years since enrollment and 12% (53) have
      experienced at least one GTC. The median time to develop GTCs from initial
      therapy was 4.7 years. The median age at first GTC was 13.1 years. Fifteen (28%)
      were not on medications at the time of their first GTC. On univariate analysis,
      older age at enrollment was associated with a higher risk of GTCs (p=-0.0009), as
      was the duration of the shortest burst on the baseline EEG (p=0.037). Failure to
      respond to initial treatment (p<0.001) but not treatment assignment was
      associated with a higher rate of GTCs. Among patients initially assigned to
      ethosuximide, 94% (15/16) with GTCs experienced initial therapy failure
      (p<0.0001). A similar but more modest effect was noted in those initially treated
      with valproate (p=0.017) and not seen in those initially treated with
      lamotrigine. CONCLUSIONS: The occurrence of GTCs in a well-characterized cohort
      of children with CAE appears lower than previously reported. GTCs tend to occur
      late in the course of the disorder. Children initially treated with ethosuximide
      who are responders have a particularly low risk of developing subsequent GTCs.

PMID- 26311756
TI  - Lymphatic filariasis among children and adolescents: spatial identification via
      socio-environmental indicators to define priority areas for elimination.
AB  - BACKGROUND: The occurrence of lymphatic filariasis (LF) and its transmission
      dynamics among children and adolescents are still not clearly elucidated. The aim
      of this study was to describe the spatial distribution of microfilaremia and its
      relationship with socio-environmental variables, thereby identifying areas at
      greater risk of transmission. METHODS: An ecological study was conducted, in
      which the analysis unit was formed by districts of the municipality of Jaboatao
      dos Guararapes in the state of Pernambuco, Brazil. The data source was a
      parasitological survey. Inadequate sewage disposal, number of people in the
      household and income of between 0.5 and 1 minimum salary were used to construct
      the socio-environmental indicator. The districts were then grouped according to
      the indicator into three risk strata, using the k-means clustering technique.
      RESULTS: In the study, 96/8670 (1.1%) of the population were found to present
      microfilaremia. The high-risk stratum had a mean prevalence rate of 1.9% and a
      risk of 2.56 (p<0.05), in relation to the low-risk stratum. The middle stratum
      grouped the households that presented an intermediate risk of transmission, with
      a prevalence rate of 1.92%. CONCLUSIONS: The indicator used is a promising tool
      that enables the precise measurement of the relationship between social
      deprivation and the prevalence of filarial infection among children. Thus, it can
      be used to plan control and elimination actions.

PMID- 26311760
TI  - Multivariate fMRI Approaches to Flexible Sensorimotor Maps in Parietal Cortex.

PMID- 26311759
TI  - The porcine sperm reservoir in relation to the function of hyaluronan.
AB  - The oviduct plays a role in successful animal reproduction not only in
      spermatozoa and ova transport to the fertilization site but also by affording a
      microenvironment for fertilization and early embryonic development. The sperm
      reservoir (SR) is restricted in the uterotubal junction (UTJ) and caudal isthmus.
      Billions of porcine spermatozoa are distributed to the female reproductive tract
      during/after insemination, and small amounts of them are stored for about 36-40
      hours in the SR, which maintains sperm viability in the pre-ovulation period
      through its surface epithelium and production of fluid. The SR regulates the
      release of spermatozoa so that only a small population moves towards the
      fertilization site (ampulla) to decrease polyspermy. This review attempts to
      provide information about the structure and function of the porcine SR, its
      intraluminal content (hyaluronan, HA), and the influences of HA on porcine
      spermatozoa in vivo. In pigs, the spermatozoa are stored in a mucous-like fluid
      within the UTJ and caudal isthmus in the pre-ovulation period. The oviduct fluid
      contains sulfated glycosaminoglycans (GAGs) and non-sulfated GAGs, i.e., HA. It
      is interesting to note that HA is synthesized by hyaluronan synthase-3 (HAS-3),
      and its receptor, CD44, is found in the epithelium of the porcine SR site.
      Additionally, sperm capacitation does not occur in vivo in the SR during the pre-
      and peri-ovulation periods, but spermatozoa in the SR will attempt to capacitate
      if exposed to bicarbonate. However, capacitation in the SR will rise in the post
      ovulation period, indicating the role of HA in modulating sperm capacitation
      after ovulation. All data support the understanding that the porcine SR ensures
      the viability of fertile spermatozoa and maintains the non-capacitated status
      during the pre-ovulation period. This basic knowledge about the SR is believed to
      be useful to advance sperm preparation procedures for in vitro fertilization
      (IVF) and improve the preservation process of porcine semen. 

PMID- 26311761
TI  - Second Language Feedback Reduces the Hot Hand Fallacy, But Why?

PMID- 26311763
TI  - Does the Brain Extrapolate the Position of a Transient Moving Target?
AB  - When an object moves in the visual field, its motion evokes a streak of activity
      on the retina and the incoming retinal signals lead to robust oculomotor commands
      because corrections are observed if the trajectory of the interceptive saccade is
      perturbed by a microstimulation in the superior colliculus. The present study
      complements a previous perturbation study by investigating, in the head
      restrained monkey, the generation of saccades toward a transient moving target
      (100-200 ms). We tested whether the saccades land on the average of antecedent
      target positions or beyond the location where the target disappeared. Using
      target motions with different speed profiles, we also examined the sensitivity of
      the process that converts time-varying retinal signals into saccadic oculomotor
      commands. The results show that, for identical overall target displacements on
      the visual display, saccades toward a faster target land beyond the endpoint of
      saccades toward a target moving slower. The rate of change in speed matters in
      the visuomotor transformation. Indeed, in response to identical overall target
      displacements and durations, the saccades have smaller amplitude when they are
      made in response to an accelerating target than to a decelerating one. Moreover,
      the motion-related signals have different weights depending upon their timing
      relative to the target onset: early signals are more influential in the
      specification of saccade amplitude than later signals. We discuss the
      "predictive" properties of the visuo-saccadic system and the nature of this
      location where the saccades land, after providing some critical comments to the
      "hic-et-nunc" hypothesis (Fleuriet and Goffart, 2012). SIGNIFICANCE STATEMENT:
      Complementing the work of Fleuriet and Goffart (2012), this study is a
      contribution to the more general scientific research aimed at understanding how
      ongoing action is dynamically and adaptively adjusted to the current
      spatiotemporal aspects of its goal. Using the saccadic eye movement as a probe,
      we provide results that are critical for investigating and understanding the
      neural basis of motion extrapolation and prediction.

PMID- 26311762
TI  - An Engineered Metal Sensor Tunes the Kinetics of Synaptic Transmission.
AB  - The Ca(2+) sensor synaptotagmin-1 (syt-1) regulates neurotransmitter release by
      interacting with anionic phospholipids. Here we test the idea that the intrinsic
      kinetics of syt-membrane interactions determine, in part, the time course of
      synaptic transmission. To tune the kinetics of this interaction, we grafted
      structural elements from the slowest isoform, syt-7, onto the fastest isoform,
      syt-1, resulting in a chimera with intermediate kinetic properties. Moreover, the
      chimera coupled a physiologically irrelevant metal, Sr(2+), to membrane fusion in
      vitro. When substituted for syt-1 in mouse hippocampal neurons, the chimera
      slowed the kinetics of synaptic transmission. Neurons expressing the chimera also
      evinced rapid and efficient Sr(2+) triggered release, in contrast to the weak
      response of neurons expressing syt-1. These findings reveal presynaptic sensor
      membrane interactions as a major factor regulating the speed of the release
      machinery. Finally, the chimera failed to clamp the elevated spontaneous fusion
      rate exhibited by syt-1 KO neurons, indicating that the metal binding loops of
      syt-1 regulate the two modes of release by distinct mechanisms. SIGNIFICANCE
      STATEMENT: In calcium, synaptotagmin-1 triggers neurotransmitter release by
      interacting with membranes. Here, we demonstrate that intrinsic properties of
      this interaction control the time course of synaptic transmission. We engineered
      a "chimera" using synaptotagmin-1 and elements of a slower isoform, synaptotagmin
      7. When expressed in neurons, the chimera slowed the rate of neurotransmitter
      release. Furthermore, unlike native synaptotagmin-1, the chimera was able to
      function robustly in the presence of strontium-a metal not present in cells. We
      exploited this ability to show that a key function of synaptotagmin-1 is to
      penetrate cell membranes. This work sheds light on fundamental mechanisms of
      neurotransmitter release.

PMID- 26311764
TI  - COX-2-Derived Prostaglandin E2 Produced by Pyramidal Neurons Contributes to
      Neurovascular Coupling in the Rodent Cerebral Cortex.
AB  - Vasodilatory prostaglandins play a key role in neurovascular coupling (NVC), the
      tight link between neuronal activity and local cerebral blood flow, but their
      precise identity, cellular origin and the receptors involved remain unclear. Here
      we show in rats that NMDA-induced vasodilation and hemodynamic responses evoked
      by whisker stimulation involve cyclooxygenase-2 (COX-2) activity and activation
      of the prostaglandin E2 (PgE2) receptors EP2 and EP4. Using liquid chromatography
      electrospray ionization-tandem mass spectrometry, we demonstrate that PgE2 is
      released by NMDA in cortical slices. The characterization of PgE2 producing cells
      by immunohistochemistry and single-cell reverse transcriptase-PCR revealed that
      pyramidal cells and not astrocytes are the main cell type equipped for PgE2
      synthesis, one third expressing COX-2 systematically associated with a PgE2
      synthase. Consistent with their central role in NVC, in vivo optogenetic
      stimulation of pyramidal cells evoked COX-2-dependent hyperemic responses in
      mice. These observations identify PgE2 as the main prostaglandin mediating
      sensory-evoked NVC, pyramidal cells as their principal source and vasodilatory
      EP2 and EP4 receptors as their targets. SIGNIFICANCE STATEMENT: Brain function
      critically depends on a permanent spatiotemporal match between neuronal activity
      and blood supply, known as NVC. In the cerebral cortex, prostaglandins are major
      contributors to NVC. However, their biochemical identity remains elusive and
      their cellular origins are still under debate. Although astrocytes can induce
      vasodilations through the release of prostaglandins, the recruitment of this
      pathway during sensory stimulation is questioned. Using multidisciplinary
      approaches from single-cell reverse transcriptase-PCR, mass spectrometry, to ex
      vivo and in vivo pharmacology and optogenetics, we provide compelling evidence
      identifying PgE2 as the main prostaglandin in NVC, pyramidal neurons as their
      main cellular source and the vasodilatory EP2 and EP4 receptors as their main
      targets. These original findings will certainly change the current view of NVC.

PMID- 26311765
TI  - TRPM2, a Susceptibility Gene for Bipolar Disorder, Regulates Glycogen Synthase
      Kinase-3 Activity in the Brain.
AB  - Bipolar disorder (BD) is a psychiatric disease that causes mood swings between
      manic and depressed states. Although genetic linkage studies have shown an
      association between BD and TRPM2, a Ca(2+)-permeable cation channel, the nature
      of this association is unknown. Here, we show that D543E, a mutation of Trpm2
      that is frequently found in BD patients, induces loss of function. Trpm2
      deficient mice exhibited BD-related behavior such as increased anxiety and
      decreased social responses, along with disrupted EEG functional connectivity.
      Moreover, the administration of amphetamine in wild-type mice evoked a notable
      increase in open-field activity that was reversed by the administration of
      lithium. However, the anti-manic action of lithium was not observed in the Trpm2(
      /-) mice. The brains of Trpm2(-/-) mice showed a marked increase in
      phosphorylated glycogen synthase kinase-3 (GSK-3), a key element in BD-like
      behavior and a target of lithium. In contrast, activation of TRPM2 induced the
      dephosphorylation of GSK-3 via calcineurin, a Ca(2+)-dependent phosphatase.
      Importantly, the overexpression of the D543E mutant failed to induce the
      dephosphorylation of GSK-3. Therefore, we conclude that the genetic dysfunction
      of Trpm2 causes uncontrolled phosphorylation of GSK-3, which may lead to the
      pathology of BD. Our findings explain the long-sought etiologic mechanism
      underlying the genetic link between Trpm2 mutation and BD. SIGNIFICANCE
      STATEMENT: Bipolar disorder (BD) is a mental disorder that causes changes in mood
      and the etiology is still unknown. TRPM2 is highly associated with BD; however,
      its involvement in the etiology of BD is still unknown. We show here that TRPM2
      plays a central role in causing the pathology of BD. We found that D543E, a
      mutation of Trpm2 frequently found in BD patients, induces the loss of function.
      Trpm2-deficient mice exhibited mood disturbances and impairments in social
      cognition. TRPM2 actively regulates the phosphorylation of GSK-3, which is a main
      target of lithium, a primary medicine for treating BD. Therefore, abnormal
      regulation of GSK-3 by hypoactive TRPM2 mutants accounts for the pathology of BD,
      providing the possible link between BD and TRPM2.

PMID- 26311766
TI  - Processing of Own Hand Visual Feedback during Object Grasping in Ventral Premotor
      Mirror Neurons.
AB  - Mirror neurons (MNs) discharge during action execution as well as during
      observation of others' actions. Our own actions are those that we have the
      opportunity to observe more frequently, but no study thus far to our knowledge
      has addressed the issue of whether, and to what extent, MNs can code own hand
      visual feedback (HVF) during object grasping. Here, we show that MNs of the
      ventral premotor area F5 of macaque monkeys are particularly sensitive to HVF
      relative to non-MNs simultaneously recorded in the same penetrations.
      Importantly, the HVF effect is more evident on MN activity during hand-object
      interaction than during the hand-shaping phase. Furthermore, the increase of MN
      activity induced by HVF and others' actions observed from a subjective
      perspective were positively correlated. These findings indicate that at least
      part of ventral premotor MNs can process the visual information coming from own
      hand interacting with objects, likely playing a role in self-action monitoring.
      SIGNIFICANCE STATEMENT: We show that mirror neurons (MNs) of area F5 of the
      macaque, in addition to encoding others' observed actions, are particularly
      sensitive, relative to simultaneously recorded non-MNs, to the sight of the
      monkey's own hand during object grasping, likely playing a role in self-action
      monitoring.

PMID- 26311767
TI  - Parvalbumin+ Neurons and Npas1+ Neurons Are Distinct Neuron Classes in the Mouse
      External Globus Pallidus.
AB  - Compelling evidence suggests that pathological activity of the external globus
      pallidus (GPe), a nucleus in the basal ganglia, contributes to the motor symptoms
      of a variety of movement disorders such as Parkinson's disease. Recent studies
      have challenged the idea that the GPe comprises a single, homogenous population
      of neurons that serves as a simple relay in the indirect pathway. However, we
      still lack a full understanding of the diversity of the neurons that make up the
      GPe. Specifically, a more precise classification scheme is needed to better
      describe the fundamental biology and function of different GPe neuron classes. To
      this end, we generated a novel multicistronic BAC (bacterial artificial
      chromosome) transgenic mouse line under the regulatory elements of the Npas1
      gene. Using a combinatorial transgenic and immunohistochemical approach, we
      discovered that parvalbumin-expressing neurons and Npas1-expressing neurons in
      the GPe represent two nonoverlapping cell classes, amounting to 55% and 27% of
      the total GPe neuron population, respectively. These two genetically identified
      cell classes projected primarily to the subthalamic nucleus and to the striatum,
      respectively. Additionally, parvalbumin-expressing neurons and Npas1-expressing
      neurons were distinct in their autonomous and driven firing characteristics,
      their expression of intrinsic ion conductances, and their responsiveness to
      chronic 6-hydroxydopamine lesion. In summary, our data argue that parvalbumin
      expressing neurons and Npas1-expressing neurons are two distinct functional
      classes of GPe neurons. This work revises our understanding of the GPe, and
      provides the foundation for future studies of its function and dysfunction.
      SIGNIFICANCE STATEMENT: Until recently, the heterogeneity of the constituent
      neurons within the external globus pallidus (GPe) was not fully appreciated. We
      addressed this knowledge gap by discovering two principal GPe neuron classes,
      which were identified by their nonoverlapping expression of the markers
      parvalbumin and Npas1. Our study provides evidence that parvalbumin and Npas1
      neurons have different topologies within the basal ganglia.

PMID- 26311768
TI  - A Distinct Population of Microglia Supports Adult Neurogenesis in the
      Subventricular Zone.
AB  - Microglia are involved in synaptic pruning both in development and in the mature
      CNS. In this study, we investigated whether microglia might further contribute to
      circuit plasticity by modulating neuronal recruitment from the neurogenic
      subventricular zone (SVZ) of the adult mouse striatum. We found that microglia
      residing in the SVZ and adjacent rostral migratory stream (RMS) comprise a
      morphologically and antigenically distinct phenotype of immune effectors. Whereas
      exhibiting characteristics of alternatively activated microglia, the SVZ/RMS
      microglia were clearly distinguished by their low expression of purinoceptors and
      lack of ATP-elicitable chemotaxis. Furthermore, the in vivo depletion of these
      microglia hampered the survival and migration of newly generated neuroblasts
      through the RMS to the olfactory bulb. SVZ and RMS microglia thus appear to
      comprise a functionally distinct class that is selectively adapted to the support
      and direction of neuronal integration into the olfactory circuitry. Therefore,
      this unique microglial subpopulation may serve as a novel target with which to
      modulate cellular addition from endogenous neural stem and progenitor cells of
      the adult brain. SIGNIFICANCE STATEMENT: Microglial cells are a specialized
      population of macrophages in the CNS, playing key roles as immune mediators. As
      integral components in the CNS, the microglia stand out for using the same
      mechanisms, phagocytosis and cytochemokine release, to promote homeostasis,
      synaptic pruning, and neural circuitry sculpture. Here, we addressed microglial
      functions in the subventricular zone (SVZ), the major postnatal neurogenic niche.
      Our results depict microglia as a conspicuous component of SVZ and its anterior
      extension, the rostral migratory stream, a pathway used by neuroblasts during
      their transit toward olfactory bulb layers. In addition to other unique
      populations residing in the SVZ niche, microglia display distinct
      morphofunctional properties that boost neuronal progenitor survival and migration
      in the mammalian brain.

PMID- 26311770
TI  - Processing and Integration of Contextual Information in Monkey Ventrolateral
      Prefrontal Neurons during Selection and Execution of Goal-Directed Manipulative
      Actions.
AB  - The prefrontal cortex (PFC) is deemed to underlie the complexity, flexibility,
      and goal-directedness of primates' behavior. Most neurophysiological studies
      performed so far investigated PFC functions with arm-reaching or oculomotor
      tasks, thus leaving unclear whether, and to which extent, PFC neurons also play a
      role in goal-directed manipulative actions, such as those commonly used by
      primates during most of their daily activities. Here we trained two macaques to
      perform or withhold grasp-to-eat and grasp-to-place actions, depending on the
      combination of two subsequently presented cues: an auditory go/no-go cue
      (high/low tone) and a visually presented target (food/object). By varying the
      order of presentation of the two cues, we could segment and independently
      evaluate the processing and integration of contextual information allowing the
      monkey to make a decision on whether or not to act, and what action to perform.
      We recorded 403 task-related neurons from the ventrolateral prefrontal cortex
      (VLPFC): unimodal sensory-driven (37%), motor-related (21%), unimodal sensory-and
      motor (23%), and multisensory (19%) neurons. Target and go/no-go selectivity
      characterized most of the recorded neurons, particularly those endowed with motor
      related discharge. Interestingly, multisensory neurons appeared to encode a
      behavioral decision independently from the sensory modality of the stimulus
      allowing the monkey to make it: some of them reflected the decision to act or
      refraining from acting (56%), whereas others (44%) encoded the decision to
      perform (or withhold) a specific action (e.g., grasp-to-eat). Our findings
      indicate that VLPFC neurons play a role in the processing of contextual
      information underlying motor decision during goal-directed manipulative actions.
      SIGNIFICANCE STATEMENT: We demonstrated that macaque ventrolateral prefrontal
      cortex (VLPFC) neurons show remarkable selectivity for different aspects of the
      contextual information allowing the monkey to select and execute goal-directed
      manipulative actions. Interestingly, a set of these neurons provide multimodal
      representations of the intended goal of a forthcoming action, encoding a
      behavioral decision (e.g., grasp-to-eat) independently from the sensory
      information allowing the monkey to make it. Our findings expand the available
      knowledge on prefrontal functions by showing that VLPFC neurons play a role in
      the selection and execution of goal-directed manipulative actions resembling
      those of common primates' foraging behaviors. On these bases, we propose that
      VLPFC may host an abstract "vocabulary" of the intended goals pursued by primates
      in their natural environment.

PMID- 26311769
TI  - Bexarotene-Activated Retinoid X Receptors Regulate Neuronal Differentiation and
      Dendritic Complexity.
AB  - Bexarotene-activated retinoid X receptors (RXRs) ameliorate memory deficits in
      Alzheimer's disease mouse models, including mice expressing human apolipoprotein
      E (APOE) isoforms. The goal of this study was to gain further insight into
      molecular mechanisms whereby ligand-activated RXR can affect or restore cognitive
      functions. We used an unbiased approach to discover genome-wide changes in RXR
      cistrome (ChIP-Seq) and gene expression profile (RNA-Seq) in response to
      bexarotene in the cortex of APOE4 mice. Functional categories enriched in both
      datasets revealed that bexarotene-liganded RXR affected signaling pathways
      associated with neurogenesis and neuron projection development. To further
      validate the significance of RXR for these functions, we used mouse embryonic
      stem (ES) cells, primary neurons, and APOE3 and APOE4 mice treated with
      bexarotene. In vitro data from ES cells confirmed that bexarotene-activated RXR
      affected neuronal development at different levels, including proliferation of
      neural progenitors and neuronal differentiation, and stimulated neurite
      outgrowth. This effect was validated in vivo by demonstrating an increased number
      of neuronal progenitors after bexarotene treatment in the dentate gyrus of APOE3
      and APOE4 mice. In primary neurons, bexarotene enhanced the dendritic complexity
      characterized by increased branching, intersections, and bifurcations. This
      effect was confirmed by in vivo studies demonstrating that bexarotene
      significantly improved the compromised dendritic structure in the hippocampus of
      APOE4 mice. We conclude that bexarotene-activated RXRs promote genetic programs
      involved in the neurogenesis and development of neuronal projections and these
      results have significance for the improvement of cognitive deficits. SIGNIFICANCE
      STATEMENT: Bexarotene-activated retinoid X receptors (RXRs) ameliorate memory
      deficits in Alzheimer's disease mouse models, including mice expressing human
      apolipoprotein E (APOE) isoforms. The goal of this study was to gain further
      insight into molecular mechanisms whereby ligand-activated RXR can affect or
      restore cognitive functions. We used an unbiased approach to discover genome-wide
      changes in RXR cistrome (ChIP-Seq) and gene expression profile (RNA-Seq) in
      response to bexarotene in the cortex of APOE4 mice. Functional categories
      enriched in both datasets revealed that liganded RXR affected signaling pathways
      associated with neurogenesis and neuron projection development. The significance
      of RXR for these functions was validated in mouse embryonic stem cells, primary
      neurons, and APOE3 and APOE4 mice treated with bexarotene.

PMID- 26311771
TI  - Spatiotemporal Profile of Voltage-Sensitive Dye Responses in the Visual Cortex of
      Tree Shrews Evoked by Electric Microstimulation of the Dorsal Lateral Geniculate
      and Pulvinar Nuclei.
AB  - The primary visual cortex (V1) receives its main thalamic drive from the dorsal
      lateral geniculate nucleus (dLGN) through synaptic contacts terminating primarily
      in cortical layer IV. In contrast, the projections from the pulvinar nucleus to
      the cortex are less clearly defined. The pulvinar projects predominantly to layer
      I in V1, and layer IV in extrastriate areas. These projection patterns suggest
      that the pulvinar nucleus most strongly influences (drives) activity in cortical
      areas beyond V1. Should this hypothesis be true, one would expect the
      spatiotemporal responses evoked by pulvinar activation to be different in V1 and
      extrastriate areas, reflecting the different connectivity patterns. We
      investigated this issue by analyzing the spatiotemporal dynamics of cortical
      visual areas' activity following thalamic electrical microstimulation in tree
      shrews, using optical imaging and voltage-sensitive dyes. As expected, electrical
      stimulation of the dLGN induced fast and local responses in V1, as well as in
      extrastriate and contralateral cortical areas. In contrast, electrical
      stimulation of the pulvinar induced fast and local responses in extrastriate
      areas, followed by weak and diffuse activation in V1 and contralateral cortical
      areas. This study highlights spatiotemporal cortical activation characteristics
      induced by stimulation of first (dLGN) and high-order (pulvinar) thalamic nuclei.
      SIGNIFICANCE STATEMENT: The pulvinar nucleus represents the main extrageniculate
      thalamic visual structure in higher-order mammals, but its exact role remains
      enigmatic. The pulvinar receive prominent inputs from virtually all visual
      cortical areas. Cortico-thalamo-cortical pathways through the pulvinar nuclei may
      then provide a complementary route for corticocortical information flow. One step
      toward the understanding of the role of transthalamic corticocortical pathways is
      to determine the nature of the signals transmitted between the cortex and the
      thalamus. By performing, for the first time, high spatiotemporal mesoscopic
      imaging on tree shrews (the primate's closest relative) through the combination
      of voltage-sensitive dye recordings and brain stimulation, we revealed clear
      evidence of distinct thalamocortical functional connectivity pattern originating
      from the geniculate nucleus and the pulvinar nuclei.

PMID- 26311772
TI  - The Contingency of Cocaine Administration Accounts for Structural and Functional
      Medial Prefrontal Deficits and Increased Adrenocortical Activation.
AB  - The prelimbic region (PL) of the medial prefrontal cortex (mPFC) is implicated in
      the relapse of drug-seeking behavior. Optimal mPFC functioning relies on synaptic
      connections involving dendritic spines in pyramidal neurons, whereas prefrontal
      dysfunction resulting from elevated glucocorticoids, stress, aging, and mental
      illness are each linked to decreased apical dendritic branching and spine density
      in pyramidal neurons in these cortical fields. The fact that cocaine use induces
      activation of the stress-responsive hypothalamo-pituitary-adrenal axis raises the
      possibility that cocaine-related impairments in mPFC functioning may be
      manifested by similar changes in neuronal architecture in mPFC. Nevertheless,
      previous studies have generally identified increases, rather than decreases, in
      structural plasticity in mPFC after cocaine self-administration. Here, we use 3D
      imaging and analysis of dendritic spine morphometry to show that chronic cocaine
      self-administration leads to mild decreases of apical dendritic branching,
      prominent dendritic spine attrition in PL pyramidal neurons, and working memory
      deficits. Importantly, these impairments were largely accounted for in groups of
      rats that self-administered cocaine compared with yoked-cocaine- and saline
      matched counterparts. Follow-up experiments failed to demonstrate any effects of
      either experimenter-administered cocaine or food self-administration on
      structural alterations in PL neurons. Finally, we verified that the cocaine self
      administration group was distinguished by more protracted increases in
      adrenocortical activity compared with yoked-cocaine- and saline-matched controls.
      These studies suggest a mechanism whereby increased adrenocortical activity
      resulting from chronic cocaine self-administration may contribute to regressive
      prefrontal structural and functional plasticity. SIGNIFICANCE STATEMENT: Stress,
      aging, and mental illness are each linked to decreased prefrontal plasticity.
      Here, we show that chronic cocaine self-administration in rats leads to
      decrements in medial prefrontal structural and functional plasticity. Notably,
      these impairments were largely accounted for in rats that self-administered
      cocaine compared with yoked counterparts. Moreover, we verified previous reports
      showing that adrenocortical output is augmented by cocaine administration and is
      more protracted in rats that were permitted to receive the drug contingently
      instead of passively. These studies suggest that increased adrenocortical
      activity resulting from cocaine self-administration may contribute to regressive
      prefrontal structural and functional plasticity.

PMID- 26311773
TI  - Detection of p75NTR Trimers: Implications for Receptor Stoichiometry and
      Activation.
AB  - The p75 neurotrophin receptor (p75(NTR)) is a multifunctional receptor that
      participates in many critical processes in the nervous system, ranging from
      apoptosis to synaptic plasticity and morphological events. It is a member of the
      tumor necrosis factor receptor (TNFR) superfamily, whose members undergo trimeric
      oligomerization. Interestingly, p75(NTR) interacts with dimeric ligands (i.e.,
      proneurotrophins or mature neurotrophins), but several of the intracellular
      adaptors that mediate p75(NTR) signaling are trimeric (i.e., TNFR-associated
      factor 6 or TRAF6). Consequently, the active receptor signaling unit remains
      uncertain. To identify the functional receptor complex, we evaluated its
      oligomerization in vitro and in mice brain tissues using a combination of
      biochemical techniques. We found that the most abundant homotypic arrangement for
      p75(NTR) is a trimer and that monomers and trimers coexist at the cell surface.
      Interestingly, trimers are not required for ligand-independent or ligand
      dependent p75(NTR) activation in a growth cone retraction functional assay.
      However, monomers are capable of inducing acute morphological effects in neurons.
      We propose that p75(NTR) activation is regulated by its oligomerization status
      and its levels of expression. These results indicate that the oligomeric state of
      p75(NTR) confers differential responses and offers an explanation for the diverse
      and contradictory actions of this receptor in the nervous system. SIGNIFICANCE
      STATEMENT: The p75 neurotrophin receptor (p75(NTR)) regulates a wide range of
      cellular functions, including apoptosis, neuronal processes remodeling, and
      synaptic plasticity. The goal of our work was to inquire whether oligomers of the
      receptor are required for function. Here we report that p75(NTR) predominantly
      assembles as a trimer, similar to other tumor necrosis factor receptors.
      Interestingly, monomers and trimers coexist at the cell surface, but trimers are
      not required for p75(NTR) activation in a functional assay. However, monomers are
      capable of inducing acute morphological effects in neurons. Identification of the
      oligomerization state of p75(NTR) begins to provide insights to the mechanisms of
      signal initiation of this noncatalytic receptor, as well as to develop
      therapeutic interventions to diminish its activity.

PMID- 26311774
TI  - A Retinotopic Basis for the Division of High-Level Scene Processing between
      Lateral and Ventral Human Occipitotemporal Cortex.
AB  - In humans, there is a repeated category-selective organization across the lateral
      and ventral surfaces of the occipitotemporal cortex. This apparent redundancy is
      often explained as a feedforward hierarchy, with processing within lateral areas
      preceding the processing within ventral areas. Here, we tested the alternative
      hypothesis that this structure better reflects distinct high-level
      representations of the upper (ventral surface) and lower (lateral surface)
      contralateral quadrants of the visual field, consistent with anatomical
      projections from early visual areas to these surfaces in monkey. Using complex
      natural scenes, we provide converging evidence from three independent functional
      imaging and behavioral studies. First, population receptive field mapping
      revealed strong biases for the contralateral upper and lower quadrant within the
      ventral and lateral scene-selective regions, respectively. Second, these same
      biases were observed in the position information available both in the magnitude
      and multivoxel response across these areas. Third, behavioral judgments of a
      scene property strongly represented within the ventral scene-selective area
      (open/closed), but not another equally salient property (manmade/natural), were
      more accurate in the upper than the lower field. Such differential representation
      of visual space poses a substantial challenge to the idea of a strictly
      hierarchical organization between lateral and ventral scene-selective regions.
      Moreover, such retinotopic biases seem to extend beyond these regions throughout
      both surfaces. Thus, the large-scale organization of high-level extrastriate
      cortex likely reflects the need for both specialized representations of
      particular categories and constraints from the structure of early vision.
      SIGNIFICANCE STATEMENT: One of the most striking findings in fMRI has been the
      presence of matched category-selective regions on the lateral and ventral
      surfaces of human occipitotemporal cortex. Here, we focus on scene-selective
      regions and provide converging evidence for a retinotopic explanation of this
      organization. Specifically, we demonstrate that scene-selective regions exhibit
      strong biases for different portions of the visual field, with the lateral region
      representing the contralateral lower visual field and the ventral region the
      contralateral upper visual field. These biases are consistent with the retinotopy
      found in the early visual areas that lie directly antecedent to category
      selective areas on both surfaces. Furthermore, these biases extend beyond scene
      selective cortex and provide a retinotopic basis for the large-scale organization
      of occipitotemporal cortex.

PMID- 26311775
TI  - Inhibition-Induced Forgetting Results from Resource Competition between Response
      Inhibition and Memory Encoding Processes.
AB  - Response inhibition is a key component of executive control, but its relation to
      other cognitive processes is not well understood. We recently documented the
      "inhibition-induced forgetting effect": no-go cues are remembered more poorly
      than go cues. We attributed this effect to central-resource competition, whereby
      response inhibition saps attention away from memory encoding. However, this
      proposal is difficult to test with behavioral means alone. We therefore used fMRI
      in humans to test two neural predictions of the "common resource hypothesis": (1)
      brain regions associated with response inhibition should exhibit greater resource
      demands during encoding of subsequently forgotten than remembered no-go cues; and
      (2) this higher inhibitory resource demand should lead to memory encoding regions
      having less resources available during encoding of subsequently forgotten no-go
      cues. Participants categorized face stimuli by gender in a go/no-go task and,
      following a delay, performed a surprise recognition memory test for those faces.
      Replicating previous findings, memory was worse for no-go than for go stimuli.
      Crucially, forgetting of no-go cues was predicted by high inhibitory resource
      demand, as quantified by the trial-by-trial ratio of activity in neural "no-go"
      versus "go" networks. Moreover, this index of inhibitory demand exhibited an
      inverse trial-by-trial relationship with activity in brain regions responsible
      for the encoding of no-go cues into memory, notably the ventrolateral prefrontal
      cortex. This seesaw pattern between the neural resource demand of response
      inhibition and activity related to memory encoding directly supports the
      hypothesis that response inhibition temporarily saps attentional resources away
      from stimulus processing. SIGNIFICANCE STATEMENT: Recent behavioral experiments
      showed that inhibiting a motor response to a stimulus (a "no-go cue") impairs
      subsequent memory for that cue. Here, we used fMRI to test whether this
      "inhibition-induced forgetting effect" is caused by competition for neural
      resources between the processes of response inhibition and memory encoding. We
      found that trial-by-trial variations in neural inhibitory resource demand
      predicted subsequent forgetting of no-go cues and that higher inhibitory demand
      was furthermore associated with lower concurrent activation in brain regions
      responsible for successful memory encoding of no-go cues. Thus, motor inhibition
      and stimulus encoding appear to compete with each other: when more resources have
      to be devoted to inhibiting action, less are available for encoding sensory
      stimuli.

PMID- 26311776
TI  - Reduced Cortical Activity Impairs Development and Plasticity after Neonatal
      Hypoxia Ischemia.
AB  - Survivors of preterm birth are at high risk of pervasive cognitive and learning
      impairments, suggesting disrupted early brain development. The limits of
      viability for preterm birth encompass the third trimester of pregnancy, a
      "precritical period" of activity-dependent development characterized by the onset
      of spontaneous and evoked patterned electrical activity that drives neuronal
      maturation and formation of cortical circuits. Reduced background activity on
      electroencephalogram (EEG) is a sensitive marker of brain injury in human preterm
      infants that predicts poor neurodevelopmental outcome. We studied a rodent model
      of very early hypoxic-ischemic brain injury to investigate effects of injury on
      both general background and specific patterns of cortical activity measured with
      EEG. EEG background activity is depressed transiently after moderate hypoxia
      ischemia with associated loss of spindle bursts. Depressed activity, in turn, is
      associated with delayed expression of glutamate receptor subunits and
      transporters. Cortical pyramidal neurons show reduced dendrite development and
      spine formation. Complementing previous observations in this model of impaired
      visual cortical plasticity, we find reduced somatosensory whisker barrel
      plasticity. Finally, EEG recordings from human premature newborns with brain
      injury demonstrate similar depressed background activity and loss of bursts in
      the spindle frequency band. Together, these findings suggest that abnormal
      development after early brain injury may result in part from disruption of
      specific forms of brain activity necessary for activity-dependent circuit
      development. SIGNIFICANCE STATEMENT: Preterm birth and term birth asphyxia result
      in brain injury from inadequate oxygen delivery and constitute a major and
      growing worldwide health problem. Poor outcomes are noted in a majority of very
      premature (<25 weeks gestation) newborns, resulting in death or life-long
      morbidity with motor, sensory, learning, behavioral, and language disabilities
      that limit academic achievement and well-being. Limited progress has been made to
      develop therapies that improve neurologic outcomes. The overall objective of this
      study is to understand the effect of early brain injury on activity-dependent
      brain development and cortical plasticity to develop new treatments that will
      optimize repair and recovery after brain injury.

PMID- 26311777
TI  - Trans-Modulation of the Somatostatin Type 2A Receptor Trafficking by Insulin
      Regulated Aminopeptidase Decreases Limbic Seizures.
AB  - Within the hippocampus, the major somatostatin (SRIF) receptor subtype, the sst2A
      receptor, is localized at postsynaptic sites of the principal neurons where it
      modulates neuronal activity. Following agonist exposure, this receptor rapidly
      internalizes and recycles slowly through the trans-Golgi network. In epilepsy, a
      high and chronic release of somatostatin occurs, which provokes, in both rat and
      human tissue, a decrease in the density of this inhibitory receptor at the cell
      surface. The insulin-regulated aminopeptidase (IRAP) is involved in vesicular
      trafficking and shares common regional distribution with the sst2A receptor. In
      addition, IRAP ligands display anticonvulsive properties. We therefore sought to
      assess by in vitro and in vivo experiments in hippocampal rat tissue whether IRAP
      ligands could regulate the trafficking of the sst2A receptor and, consequently,
      modulate limbic seizures. Using pharmacological and cell biological approaches,
      we demonstrate that IRAP ligands accelerate the recycling of the sst2A receptor
      that has internalized in neurons in vitro or in vivo. Most importantly, because
      IRAP ligands increase the density of this inhibitory receptor at the plasma
      membrane, they also potentiate the neuropeptide SRIF inhibitory effects on
      seizure activity. Our results further demonstrate that IRAP is a therapeutic
      target for the treatment of limbic seizures and possibly for other neurological
      conditions in which downregulation of G-protein-coupled receptors occurs.
      SIGNIFICANCE STATEMENT: The somatostatin type 2A receptor (sst2A) is localized on
      principal hippocampal neurons and displays anticonvulsant properties. Following
      agonist exposure, however, this receptor rapidly internalizes and recycles
      slowly. The insulin-regulated aminopeptidase (IRAP) is involved in vesicular
      trafficking and shares common regional distribution with the sst2A receptor. We
      therefore assessed by in vitro and in vivo experiments whether IRAP could
      regulate the trafficking of this receptor. We demonstrate that IRAP ligands
      accelerate sst2A recycling in hippocampal neurons. Because IRAP ligands increase
      the density of sst2A receptors at the plasma membrane, they also potentiate the
      effects of this inhibitory receptor on seizure activity. Our results further
      demonstrate that IRAP is a therapeutic target for the treatment of limbic
      seizures.

PMID- 26311779
TI  - Temporal Structure of Neuronal Activity among Cortical Neuron Subtypes during
      Slow Oscillations in Anesthetized Rats.
AB  - Slow-wave oscillations, the predominant brain rhythm during sleep, are composed
      of Up/Down cycles. Depolarizing Up-states involve activity in layer 5 (L5) of the
      neocortex, but it is unknown how diverse subtypes of neurons within L5
      participate in generating and maintaining Up-states. Here we compare the in vivo
      firing patterns of corticopontine (CPn) pyramidal cells, crossed-corticostriatal
      (CCS) pyramidal cells, and fast-spiking (FS) GABAergic neurons in the rat frontal
      cortex, with those of thalamocortical neurons during Up/Down cycles in the
      anesthetized condition. During the transition from Down- to Up-states, increased
      activity in these neurons was highly temporally structured, with spiking
      occurring first in thalamocortical neurons, followed by cortical FS cells, CCS
      cells, and, finally, CPn cells. Activity in some FS, CCS, and CPn neurons
      occurred in phase with Up-nested gamma rhythms, with FS neurons showing phase
      delay relative to pyramidal neurons. These results suggest that thalamic and
      cortical pyramidal neurons are activated in a specific temporal sequence during
      Up/Down cycles, but cortical pyramidal cells are activated at a similar gamma
      phase. In addition to Up-state firing specificity, CCS and CPn cells exhibited
      differences in activity during cortical desynchronization, further indicating
      projection- and state-dependent information processing within L5. SIGNIFICANCE
      STATEMENT: Patterned activity in neocortical electroencephalograms, including
      slow waves and gamma oscillations, is thought to reflect the organized activity
      of neocortical neurons that comprises many specialized neuron subtypes. We found
      that the timing of action potentials during slow waves in individual cortical
      neurons was correlated with their laminar positions and axonal targets. Within
      gamma cycles nested in the slow-wave depolarization, cortical pyramidal cells
      fired earlier than did interneurons. At the start of slow-wave depolarizations,
      activity in thalamic neurons receiving inhibition from the basal ganglia occurred
      earlier than activity in cortical neurons. Together, these findings reveal a
      temporally ordered pattern of output from diverse neuron subtypes in the frontal
      cortex and related thalamic nuclei during neocortical oscillations.

PMID- 26311778
TI  - Pathways for Emotions: Specializations in the Amygdalar, Mediodorsal Thalamic,
      and Posterior Orbitofrontal Network.
AB  - The primate amygdala projects to posterior orbitofrontal cortex (pOFC) directly
      and possibly indirectly through a pathway to the magnocellular mediodorsal
      thalamic nucleus (MDmc), which may convey signals about the significance of
      stimuli. However, because MDmc receives input from structures in addition to the
      amygdala and MDmc projects to areas in addition to pOFC, it is unknown whether
      amygdalar pathways in MDmc innervate pOFC-bound neurons. We addressed this issue
      using double- or triple-labeling approaches to identify pathways and key cellular
      and molecular features in rhesus monkeys. We found that amygdalar terminations
      innervated labeled neurons in MDmc that project to pOFC. Projection neurons in
      MDmc directed to pOFC included comparatively fewer "core" parvalbumin neurons
      that project focally to the middle cortical layers and more "matrix" calbindin
      neurons that project expansively to the upper cortical layers. In addition, a
      small and hitherto unknown pathway originated from MDmc calretinin neurons and
      projected to pOFC. Further, whereas projection neurons directed to MDmc and to
      pOFC were intermingled in the amygdala, none projected to both structures. Larger
      amygdalar neurons projected to MDmc and expressed the vesicular glutamate
      transporter 2 (VGLUT2), which is found in highly efficient "driver" pathways. In
      contrast, smaller amygdalar neurons directed to pOFC expressed VGLUT1 found in
      modulatory pathways. The indirect pathway from the amygdala to pOFC via MDmc may
      provide information about the emotional significance of events and, along with a
      parallel direct pathway, ensures transfer of signals to all layers of pOFC.
      SIGNIFICANCE STATEMENT: The amygdala-the brain's center for emotions-is strongly
      linked with the orbital cortex, a region associated with social interactions.
      This study provides evidence that a robust pathway from the amygdala reaches
      neurons in the thalamus that link directly with the orbital cortex, forming a
      tight tripartite network. The dual pathways from the amygdala to the orbital
      cortex and to the thalamus are distinct by morphology, neurochemistry, and
      function. This tightly linked network suggests the presence of fool-proof avenues
      for emotions to influence high-order cortical areas associated with affective
      reasoning. Specific nodes of this tripartite network are disrupted in psychiatric
      diseases, divorcing areas that integrate emotions and thoughts for decisions and
      flexible behavior.

PMID- 26311782
TI  - Computation of Object Size in Visual Cortical Area V4 as a Neural Basis for Size
      Constancy.
AB  - Even when we view an object from different distances, so that the size of its
      projection onto the retina varies, we perceive its size to be relatively
      unchanged. In this perceptual phenomenon known as size constancy, the brain uses
      both distance and retinal image size to estimate the size of an object. Given
      that binocular disparity, the small positional difference between the retinal
      images in the two eyes, is a powerful visual cue for distance, we examined how it
      affects neuronal tuning to retinal image size in visual cortical area V4 of
      macaque monkeys. Depending on the imposed binocular disparity of a circular patch
      embedded in random dot stereograms, most neurons adjusted their preferred size in
      a manner consistent with size constancy. They preferred larger retinal image
      sizes when stimuli were stereoscopically presented nearer and preferred smaller
      retinal image sizes when stimuli were presented farther away. This disparity
      dependent shift of preferred image size was not affected by the vergence angle, a
      cue for the fixation distance, suggesting that different V4 neurons compute
      object size for different fixation distances rather than that individual neurons
      adjust the shift based on vergence. This interpretation was supported by a simple
      circuit model, which could simulate the shift of preferred image size without any
      information about the fixation distance. We suggest that a population of V4
      neurons encodes the actual size of objects, rather than simply the size of their
      retinal images, and that these neurons thereby contribute to size constancy.
      SIGNIFICANCE STATEMENT: We perceive the size of an object to be relatively stable
      despite changes in the size of its retinal image that accompany changes in
      viewing distance. This phenomenon, called size constancy, is accomplished by
      combining retinal image size and distance information in our brain. We
      demonstrate that a large population of V4 neurons changes their size tuning
      depending on the perceived distance of a visual stimulus derived from binocular
      disparity. They prefer larger or smaller retinal image sizes when stimuli are
      stereoscopically presented nearer or farther away, respectively. This property
      makes V4 neurons suitable for encoding the actual size of objects, not simply the
      retinal image sizes, and providing a possible mechanism for perceptual size
      constancy.

PMID- 26311780
TI  - Defects of Lipid Synthesis Are Linked to the Age-Dependent Demyelination Caused
      by Lamin B1 Overexpression.
AB  - Lamin B1 is a component of the nuclear lamina and plays a critical role in
      maintaining nuclear architecture, regulating gene expression and modulating
      chromatin positioning. We have previously shown that LMNB1 gene duplications
      cause autosomal dominant leukodystrophy (ADLD), a fatal adult onset demyelinating
      disease. The mechanisms by which increased LMNB1 levels cause ADLD are unclear.
      To address this, we used a transgenic mouse model where Lamin B1 overexpression
      is targeted to oligodendrocytes. These mice showed severe vacuolar degeneration
      of the spinal cord white matter together with marked astrogliosis, microglial
      infiltration, and secondary axonal damage. Oligodendrocytes in the transgenic
      mice revealed alterations in histone modifications favoring a transcriptionally
      repressed state. Chromatin changes were accompanied by reduced expression of
      genes involved in lipid synthesis pathways, many of which are known to play
      important roles in myelin regulation and are preferentially expressed in
      oligodendrocytes. Decreased lipogenic gene expression resulted in a significant
      reduction in multiple classes of lipids involved in myelin formation. Many of
      these gene expression changes and lipid alterations were observed even before the
      onset of the phenotype, suggesting a causal role. Our findings establish, for the
      first time, a link between LMNB1 and lipid synthesis in oligodendrocytes, and
      provide a mechanistic framework to explain the age dependence and white matter
      involvement of the disease phenotype. These results have implications for disease
      pathogenesis and may also shed light on the regulation of lipid synthesis
      pathways in myelin maintenance and turnover. SIGNIFICANCE STATEMENT: Autosomal
      dominant leukodystrophy (ADLD) is fatal neurological disorder caused by increased
      levels of the nuclear protein, Lamin B1. The disease is characterized by an age
      dependent loss of myelin, the fatty sheath that covers nerve fibers. We have
      studied a mouse model where Lamin B1 level are increased in oligodendrocytes, the
      cell type that produces myelin in the CNS. We demonstrate that destruction of
      myelin in the spinal cord is responsible for the degenerative phenotype in our
      mouse model. We show that this degeneration is mediated by reduced expression of
      lipid synthesis genes and the subsequent reduction in myelin enriched lipids.
      These findings provide a mechanistic framework to explain the age dependence and
      tissue specificity of the ADLD disease phenotype.

PMID- 26311783
TI  - Oncostatin M Confers Neuroprotection against Ischemic Stroke.
AB  - Cell-surface receptors provide potential targets for the translation of bench
      side findings into therapeutic strategies; however, this approach for the
      treatment of stroke is disappointing, at least partially due to an incomplete
      understanding of the targeted factors. Previous studies of oncostatin M (OSM), a
      member of the gp130 cytokine family, have been limited, as mouse models alone may
      not strongly resemble the human condition enough. In addition, the precise
      function of OSM in the CNS remains unclear. Here, we report that human OSM is
      neuroprotective in vivo and in vitro by recruiting OSMRbeta in the setting of
      ischemic stroke. Using gain- and loss-of-function approaches, we demonstrated
      that decreased neuronal OSMRbeta expression results in deteriorated stroke
      outcomes but that OSMRbeta overexpression in neurons is cerebroprotective.
      Moreover, administering recombinant human OSM to mice before the onset of I/R
      showed that human OSM can be protective in rodent models of ischemic stroke.
      Mechanistically, OSM/OSMRbeta activate the JAK2/STAT3 prosurvival signaling
      pathway. Collectively, these data support that human OSM may represent a
      promising drug candidate for stroke treatment. SIGNIFICANCE STATEMENT: OSM, a
      member of the gp130 cytokine family, regulates neuronal function and survival.
      OSM engages a second receptor, either LIFRalpha or OSMRbeta, before recruiting
      gp130. However, it is not clear whether OSM/OSMRbeta signaling is involved in
      neuroprotection in the setting of ischemic stroke. Recent studies show that,
      compared with mouse disease models, the OSM receptor system in rats more closely
      resembles that in humans. In the present study, we use genetic manipulations of
      OSMRbeta in both mouse and rat stroke models to demonstrate that OSMRbeta in
      neurons is critical for neuronal survival during cerebral ischemic/reperfusion.
      Interestingly, administration of human OSM also leads to improved stroke
      outcomes. Therefore, OSM may represent a promising drug candidate for stroke
      treatment.

PMID- 26311785
TI  - Author-Initiated Retraction: Anderson et al., Precision in visual working memory
      reaches a stable plateau when individual item limits are exceeded.
AB  - At the request of the authors, The Journal of Neuroscience is retracting
      "Precision in Visual Working Memory Reaches a Stable Plateau When Individual Item
      Limits Are Exceeded" by David E. Anderson, Edward K. Vogel, and Edward Awh, which
      appeared on pages 1128-1138 of the January 19, 2011 issue.

PMID- 26311784
TI  - IGF-1R Reduction Triggers Neuroprotective Signaling Pathways in Spinal Muscular
      Atrophy Mice.
AB  - Spinal muscular atrophy (SMA) is a neuromuscular disease characterized by the
      selective loss of spinal motor neurons due to the depletion of the survival of
      motor neuron (SMN) protein. No therapy is currently available for SMA, which
      represents the leading genetic cause of death in childhood. In the present study,
      we report that insulin-like growth factor-1 receptor (Igf-1r) gene expression is
      enhanced in the spinal cords of SMA-like mice. The reduction of expression,
      either at the physiological (through physical exercise) or genetic level,
      resulted in the following: (1) a significant improvement in lifespan and motor
      behavior, (2) a significant motor neuron protection, and (3) an increase in SMN
      expression in spinal cord and skeletal muscles through both transcriptional and
      posttranscriptional mechanisms. Furthermore, we have found that reducing IGF-1R
      expression is sufficient to restore intracellular signaling pathway activation
      profile lying downstream of IGF-1R, resulting in both the powerful activation of
      the neuroprotective AKT/CREB pathway and the inhibition of the ERK and JAK
      pathways. Therefore, reducing rather than enhancing the IGF-1 pathway could
      constitute a useful strategy to limit neurodegeneration in SMA. SIGNIFICANCE
      STATEMENT: Recent evidence of IGF-1 axis alteration in spinal muscular atrophy
      (SMA), a very severe neurodegenerative disease affecting specifically the motor
      neurons, have triggered a renewed interest in insulin-like growth factor-1 (IGF
      1) pathway activation as a potential therapeutic approach for motor neuron
      diseases. The present study challenges this point of view and brings the
      alternative hypothesis that reducing rather than enhancing the IGF-1 signaling
      pathway exerts a neuroprotective effect in SMA. Furthermore, the present data
      substantiate a newly emerging concept that the modulation of IGF-1 receptor
      expression is a key event selectively determining the activation level of
      intracellular pathways that lie downstream of the receptor. This aspect should be
      considered when designing IGF-1-based treatments for neurodegenerative diseases.

PMID- 26311781
TI  - Myelin Proteolipid Protein Complexes with alphav Integrin and AMPA Receptors In
      Vivo and Regulates AMPA-Dependent Oligodendrocyte Progenitor Cell Migration
      through the Modulation of Cell-Surface GluR2 Expression.
AB  - In previous studies, stimulation of ionotropic AMPA/kainate glutamate receptors
      on cultured oligodendrocyte cells induced the formation of a signaling complex
      that includes the AMPA receptor, integrins, calcium-binding proteins, and,
      surprisingly, the myelin proteolipid protein (PLP). AMPA stimulation of cultured
      oligodendrocyte progenitor cells (OPCs) also caused an increase in OPC migration.
      The current studies focused primarily on the formation of the PLP-alphav integrin
      AMPA receptor complex in vivo and whether complex formation impacts OPC migration
      in the brain. We found that in wild-type cerebellum, PLP associates with alphav
      integrin and the calcium-impermeable GluR2 subunit of the AMPA receptor, but in
      mice lacking PLP, alphav integrin did not associate with GluR2. Live imaging
      studies of OPC migration in ex vivo cerebellar slices demonstrated altered OPC
      migratory responses to neurotransmitter stimulation in the absence of PLP and
      GluR2 or when alphav integrin levels were reduced. Chemotaxis assays of purified
      OPCs revealed that AMPA stimulation was neither attractive nor repulsive but
      clearly increased the migration rate of wild-type but not PLP null OPCs. AMPA
      receptor stimulation of wild-type OPCs caused decreased cell-surface expression
      of the GluR2 AMPA receptor subunit and increased intracellular Ca(2+) signaling,
      whereas PLP null OPCs did not reduce GluR2 at the cell surface or increase Ca(2+)
      signaling in response to AMPA treatment. Together, these studies demonstrate that
      PLP is critical for OPC responses to glutamate signaling and has important
      implications for OPC responses when levels of glutamate are high in the
      extracellular space, such as following demyelination. SIGNIFICANCE STATEMENT:
      After demyelination, such as occurs in multiple sclerosis, remyelination of axons
      is often incomplete, leading to loss of neuronal function and clinical
      disability. Remyelination may fail because oligodendrocyte precursor cells (OPCs)
      do not completely migrate into demyelinated areas or OPCs in lesions may not
      mature into myelinating oligodendrocytes. We have found that the myelin
      proteolipid protein is critical to regulating OPC migratory responses to the
      neurotransmitter glutamate through modulation of cell-surface expression of the
      calcium-impermeable GluR2 subunit of the AMPA glutamate receptor and increased
      intercellular Ca(2+) signaling. Altered glutamate homeostasis has been reported
      in demyelinated lesions. Therefore, understanding how OPCs respond to glutamate
      has important implications for treatment after white matter injury and disease.

PMID- 26311786
TI  - Phylogenetic analysis of three orf virus strains isolated from different
      districts in Shandong Province, East China.
AB  - Orf virus (ORFV) is the causative agent of contagious ecthyma, which is a
      zoonotic disease that affects sheep, goats, wild small ruminants and humans.
      Shandong Province in East China is one of the main producing areas in China for
      sheep and goats. Here, we conducted epidemiological surveys in different areas in
      this Province, isolated three orf virus strains, SDLC, SDTA and SDJN, from goat
      flocks and then analyzed the genetic evolution of these strains. The ORFV011,
      ORFV059, ORFV109, ORFV110 and ORFV127 genes of these three strains were
      amplified, sequenced and analyzed. Phylogenetic analysis showed that ORFV011 of
      the SDLC and SDTA strains cluster together with the Gansu, Liaoning, Shanxi,
      Nantou, Hoping and FJ-YX strains, while SDJN clusters with the FJ-GS and FJ-GO
      strains. ORFV059 of the SDLC and SDTA strains cluster together with the FJ-YX
      strain, while SDJN clusters with the FJ-GS and FJ-GO strains. ORFV059 and ORFV127
      of these three strains were similar to those of the OV-SA00 strain. The results
      suggested that SDLC, SDTA and SDJN originated from Fujian Province and formed a
      complex group of viruses in Shandong Province. As the role of ORFV127 gene
      responsible for the immune evasion of ORFV, the pathogenesis of these three virus
      strains may similar to that of OV-SA00. These three strains first isolated in
      Shandong Province are novel ORFV strains, and the data reported here will be
      helpful for further research about ORFV and its comprehensive prevention and
      control. 

PMID- 26311787
TI  - Effects of oral orbifloxacin on fecal coliforms in healthy cats: a pilot study.
AB  - The study objective was to determine the effect of oral orbifloxacin (ORB) on
      antimicrobial susceptibility and composition of fecal coliforms in cats. Nine
      cats were randomized to two groups administered a daily oral dose of 2.5 and 5.0
      mg ORB/kg for 7 days and a control group (three cats per group). Coliforms were
      isolated from stool samples and were tested for susceptibilities to ORB and 5
      other drugs. ORB concentration in feces was measured using high-performance
      liquid chromatography (HPLC). The coliforms were undetectable after 2 days of ORB
      administration, and their number increased in most cats after termination of the
      administration. Furthermore, only isolates of Escherichia coli were detected in
      all cats before administration, and those of Citrobacter freundii were detected
      after termination of the administration. E. coli isolates exhibited high ORB
      susceptibility [Minimum inhibitory concentration (MIC), <=0.125 ug/ml] or
      relatively low susceptibility (MIC, 1-2 ug/ml) with a single gyrA mutation. C.
      freundii isolates largely exhibited intermediate ORB susceptibility (MIC, 4
      ug/ml), in addition to resistance to ampicillin and cefazolin, and harbored qnrB,
      but not a gyrA mutation. HPLC revealed that the peaks of mean concentration were
      61.3 and 141.0 ug/g in groups receiving 2.5 and 5.0 mg/kg, respectively. Our
      findings suggest that oral ORB may alter the total counts and composition of
      fecal coliform, but is unlikely to yield highly fluoroquinolone-resistant mutants
      of E. coli and C. freundii in cats, possibly because of the high drug
      concentration in feces. 

PMID- 26311790
TI  - Speech at the closing ceremony of Nordic School of Public Health.

PMID- 26311789
TI  - Making history: the public health legacy of Nordic School of Public Health NHV.

PMID- 26311791
TI  - Aspects from the Deans on the Nordic School of Public Health.

PMID- 26311792
TI  - How to create and terminate a school of public health.
AB  - The famous preamble to the Constitution of the World Health Organization (WHO)
      from 1948, stating that health is not only the absence of disease, has been one
      of the most influential political statements of our time. The follow-up, reaching
      a position where health is viewed as instrumental to a good life and not as a
      goal in itself, as set out in the Ottawa Charter of 1986, has likewise been of
      the utmost importance for the global development of public health, as well as
      developing the concept of health promotion. The focus on public health sparked by
      the WHO was paralleled by expansion of the academic interest in the topic,
      beginning in the USA and successively adopted around the world. In the Nordic
      countries the pioneering of an academic platform for public health studies and
      research began in 1953. This was later followed by a stepwise expansion to a full
      academic institution with postgraduate studies, work-related training, research
      and development. From the start, the resultant institution called the Nordic
      School of Public Health (NHV) was a joint Nordic project financed by the Nordic
      governments. The NHV became a leader in public health studies in Nordic countries
      and also a role model for the development of an academic community. A large
      campus and a select and erudite staff, together with thousands of students, paved
      the way for the NHV having a major impact on public health policy in Nordic
      countries. One effect of this was increasing awareness of the need for systematic
      policy supporting public health research and, with this, the founding of
      institutions of public health in all of the separate Nordic countries.
      Ironically, the impact made by the NHV in spreading the idea of public health as
      an important part of academic study has made the NHV superfluous. It is true that
      courses and programmes in public health are now available at most universities in
      the five Nordic countries, but they are directed at young students fresh from
      high school. There is no institution that offers a broad and high-quality
      postgraduate education and training in public health, adapted to the special
      needs of mid-career professionals in a multi-professional and internordic
      setting. With the NHV closing, a research institute focusing public health in a
      Nordic context will disappear, as will an internationally leading School of
      Public Health, a centre of excellence and relevance in public health, which has
      evaluated, assessed and promoted the goals and evaluated the success of the
      Nordic welfare societies. 

PMID- 26311793
TI  - On education and pedagogic development at NHV.
AB  - The role and development of the Nordic School of Public Health (NHV) during its
      60 year existence with special emphasis on the pedagogical basis (Scandinavian
      pedagogy) of courses, the student population, cross-borders incorporation of
      staff and professional and institution identity-creation through storytelling. 

PMID- 26311794
TI  - Epidemiology and statistics at the Nordic School of Public Health: Teaching and
      research 1979-2014.
AB  - The Nordic School of Public Health (NHV) was jointly founded in 1953 by the
      Nordic countries. Until 1979, the school provided ad hoc courses on public health
      topics, using external teachers drawn mainly from the Nordic countries. At the
      time, the permanent staff of the school was small. In 1979, it began a Master's
      degree programme and a few academic positions were established and filled, to
      support these courses. The programme included four main areas: Epidemiology,
      Social Medicine, Environmental Health and Health Services Administration.
      Epidemiology was compulsory in all Master of Public Health (MPH) exams, but there
      were a handful of optional courses that could be substituted for the other
      subjects.This paper tells the story of Epidemiology at NHV from about 1980, up
      until closure of the school in 2014. The original MPH model ran until 1995.
      Nursing Science entered NHV from about 1985 and worked mainly with qualitative
      research that often focused on individual patients. The new methods attracted
      nurses, midwives, psychologists and other groups that previously had been less
      represented in NHV. Being quantitative and population oriented, Epidemiology lost
      its unique position as a mandatory subject for the MPH examination. In addition
      the 'New Public Health' proposed by the World Health Organisation (WHO) that
      advocated health promotion and the philosophy of salutogenesis became a challenge
      for the programme in epidemiology: pathogenesis no longer was of primary
      interest. From 1995, the MPH format changed repeatedly and a DrPH programme was
      begun. For the last 8 years of its existence, NHV offered a reasonably
      comprehensive, basic course in Epidemiology.Throughout the years, epidemiology
      training and research at NHV were very traditional. In being a relatively free
      institution in terms of academic choices, NHV should have contributed to the
      development and innovation of epidemiology in public health. For several reasons,
      this did not happen. 

PMID- 26311795
TI  - NHV and child public health.
AB  - One of the main interests of the Nordic School of Public Health (NHV) in both
      education and research was child public health, i.e. an area based on the broad
      World Health Organisation (WHO) health ideology and on public health methods,
      while concentrating on the special needs and characteristics of children. The
      fields of study and action, training, research and service, had the ultimate task
      to consider the health of children in their full social, economic and political
      context. Regular courses on child public health were offered as part of the
      general program in Public Health from 1979 until the closing down of the school,
      named: Social Paediatrics; Child Health; Child Public Health; and finally,
      Measuring Children's Health - A Public Health Perspective. Numerous national,
      Nordic and international conferences were held, and several textbooks were
      written and edited. A major research project, NordChild, was initiated as a cross
      sectional postal study of a random sample of children aged 2-17 years from the
      five Nordic countries, performed in 1984, 1996 and 2011. So far, 10 doctoral
      theses and more than 130 other publications from the studies have been produced.
      Furthermore, the Nordic Network on Research of Refugee Children was created, and
      a special interest has been devoted to indicators for children's health, both
      internationally, nationally and locally, which has been demonstrated in major EU
      projects as well as locally in Sweden and Greenland. 

PMID- 26311796
TI  - Health services management and research at Nordic School of Public Health.
AB  - In Anglo-Saxon countries the subject of health services research has long been an
      important academic theme. In the Nordic countries, however, this research and
      training area has been limited and partly hidden by integration into various
      other sections at universities and colleges. In this respect the Nordic School of
      Public Health was an exception, as the provision of managerial skills to
      healthcare professionals and persons working with public health was the backbone
      of the school during all 60 years. A variety of research in health services
      management, as well as publications of text books, accompanied the presented
      courses. Several of the scholars have earned important positions in international
      networks and editorial boards, as well as in boards for assessments of research
      grants. In the near future, this academic field will require alternative support.

PMID- 26311797
TI  - Nordic School of Public Health NHV and its legacy in global health.
AB  - This article describes the legacy of the Nordic School of Public Health NHV (NHV)
      in global health. We delineate how this field developed at NHV and describe
      selected research and research training endeavours with examples from Vietnam and
      Nepal as well as long-term teaching collaborations such as BRIMHEALTH (Baltic RIM
      Partnership for Public HEALTH) in the Baltic countries and Arkhangelsk
      International School of Public Health in Russia. 

PMID- 26311798
TI  - Health Promotion: A developing focus area over the years.
AB  - In 1953 when the Nordic School of Public Health was founded, the aim of public
      health programmes was disease prevention more than health promotion. This was not
      unusual, since at this time health usually was seen as the opposite of disease
      and illness. However, with the Ottawa Charter of 1986, the World Health
      Organization made a crucial change to view health not as a goal in itself but as
      the means to a full life. In this way, health promotion became a first priority
      and fundamental action for the modern society. This insight eventually reached
      NHV and in 2002 - 50 years after the foundation - an associate professorship was
      established with a focus on health promotion. Nevertheless, the concept of health
      promotion had been integrated with or mentioned in courses run prior to the new
      post. Subsequently, a wide spectrum of courses in health promotion was
      introduced, such as 'Empowerment for Child and Adolescent Health Promotion',
      'Salutogenesis--from theory to practice' and 'Health, Stress and Coping'. More
      than half of all doctoral theses undertaken at NHV during these years had health
      promotion as their theme. As a derivative, the Nordic Health Promotion Research
      Network (NHPRN) was established in 2007 with bi-annual meetings at NHV.

PMID- 26311799
TI  - The Nordic Health Promotion Research Network (NHPRN).
AB  - The Nordic Health Promotion Research Network (NHPRN) was established in 2007 at
      the Nordic School of Public Health (NHV). This article aims to describe the
      foundation of the NHPRN, the development and the present status of the work of
      NHPRN. The NHPRN consists of about 50 senior and junior researchers from all
      Nordic countries. It is a working network that aims to develop the theoretical
      understanding of health promotion, to create research cooperation in health
      promotion from a Nordic perspective and to extend the scope of health promotion
      through education. Network members meet biannually to discuss and further develop
      research within the field and are also responsible for the Nordic conference on
      Health Promotion, organized every 3 years. The NHV hosted the network between
      2007 and 2014; and the World Health Organisation (WHO) will assume this role in
      2015. 

PMID- 26311800
TI  - Healthy ageing, narrative method and research ethics.
AB  - The purpose of this article is to describe research and teaching activities
      related to healthy ageing, narrative methods and research ethics at the Nordic
      School of Public Health NHV during 1999 - 2012. Healthy ageing was conceived in
      terms of The World Health Organization's (WHO) model of active ageing and of
      quality of life defined as a sense of well-being, meaning and value. Qualitative
      research on ageing and health conducted at NHV showed how elderly people
      themselves experience health and what they perceive to be health promoting.
      Narrative method was one the qualitative methods used in research at NHV. By
      adopting holistic and categorical content analysis the life stories of elderly
      Finnish migrants, the stories of home-dwelling persons about falls, and working
      persons' stories of alcohol use were studied. The courses on research ethics took
      their point of departure in a model that describes the role of scientific,
      economic, aesthetic and ethical values in research. 

PMID- 26311801
TI  - Method development at Nordic School of Public Health NHV: Phenomenology and
      Grounded Theory.
AB  - BACKGROUND: Qualitative methods such as phenomenology and grounded theory have
      been valuable tools in studying public health problems. AIM: A description and
      comparison of these methods. RESULTS: Phenomenology emphasises an inside
      perspective in form of consciousness and subjectively lived experiences, whereas
      grounded theory emanates from the idea that interactions between people create
      new insights and knowledge. Fundamental aspects of phenomenology include life
      world, consciousness, phenomenological reduction and essence. Significant
      elements in grounded theory are coding, categories and core categories, which
      develop a theory. CONCLUSIONS: There are differences in the philosophical
      approach, the name of the concept and the systematic tools between the methods.
      Thus, the phenomenological method is appropriate when studying emotional and
      existential research problems, and grounded theory is a method more suited to
      investigate processes.

PMID- 26311802
TI  - Contribution of the Nordic School of Public Health to the public mental health
      research field: a selection of research initiatives, 2007-2014.
AB  - The field of public mental health has been defined by an expert group convened by
      the Nordic School of Public Health (NHV) as encompassing the experience,
      occurrence, distribution and trajectories of positive mental health and mental
      health problems and their determinants; mental health promotion and prevention of
      mental disorders; as well as mental health system policies, governance and
      organization. The mental health priorities of the Nordic Council of Ministers in
      2010 signalled a mutual Nordic exchange of knowledge in the following thematic
      areas: child and adolescent mental health; working life and mental health; mental
      health in older people; strengthening the role of primary care in mental health
      service provision; stronger involvement of users and carers; and reduction of use
      of coercion in psychiatric care. Efforts to realize these priorities included
      commissioning the Nordic Research Academy for Mental Health, an NHV-based network
      of research institutions with a common interest in mental health research across
      the Nordic countries, to develop, organize and follow-up projects on public
      mental health. The research initiatives included mental health policy analysis,
      register-based research and research focused on the users' perspective in a
      Nordic context, as well as EU-level research policy analysis. The public mental
      health research conducted at the NHV highlighted the complexity of mental health
      and emphasized that the broad determinants of mental health need to be
      increasingly addressed in both public health research and practice. For example,
      health promotion actions, improved access to health care, a healthy alcohol
      policy and prevention of suicides and violence are all needed to reduce the life
      expectancy gap - a red flag indicator of public health inequalities. By
      exchanging knowledge and best practice, the collaboration between the Nordic
      countries contributes to the welfare of the region. The expertise and traditions
      developed at the NHV are of significant importance in this work. 

PMID- 26311803
TI  - Pharmacoepidemiology at Nordic School of Public Health NHV: Examples from 1999 to
      2014.
AB  - BACKGROUND: Pharmacoepidemiology is a branch of public health and had a place at
      the Nordic School of Public Health. Courses, Master's theses and Doctorates of
      Public Health (DrPH) in Pharmacoepidemiology were a relatively minor, but still
      important part of the school's activities. METHODS: This paper gives a short
      background, followed by some snapshots of the activities at NHV, and then some
      illustrative case-studies. These case-studies list their own responsible co
      authors and have separate reference lists. RESULTS: In the Nordic context, NHV
      was a unique provider of training and research in pharmacoepidemiology, with
      single courses to complete DrPH training, as well as implementation of externally
      funded research projects. CONCLUSIONS: With the closure of NHV at the end of
      2014, it is unclear if such a comprehensive approach towards pharmacoepidemiology
      will be found elsewhere in the Nordic countries.

PMID- 26311804
TI  - Disability from a public health perspective.
AB  - At the Nordic School of Public Health (NHV), methods to alleviate problems with
      disability have been seen as an important part of actions to support public
      health. A programme for universal design was started in 2006. Some issues of
      public health perspectives on disability are presented in this paper, based on
      discussions from a PhD course held at the NHV. During the course, the students
      presented papers in which they reflected on the relationship between disability
      and public health. These essays were collected and published in 2012 at NHV. 

PMID- 26311805
TI  - A new theme within public health science for increased life quality.
AB  - In 2006 the Nordic Council of Ministers concluded that there was need for
      education and training in how to plan and design society to enable people to live
      active, independent, and full lives without adding supplementary, segregating
      adjustments or expensive specialised solutions, especially for the elderly or
      persons with disabilities. The universal design (UD) concept became a public
      health issue for all Nordic countries. The first academic educational-training
      initiative in universal design was initiated at the Nordic School of Public
      Health (NHV) in 2006. Thereafter, a number of UD courses were held for
      professionals mainly from the Nordic countries who worked with development and
      creation of the public arena. In 2011 the first diploma programme in universal
      design was established at NHV. A new field in public health research was also
      established and a number of publications in scientific journals, presentations at
      Nordic and international conferences, together with seminars and workshops have
      established a solid ground for further development of the field in the Nordic
      countries. 

PMID- 26311806
TI  - From a student with love.

PMID- 26311807
TI  - Nordic School of Public Health may close, but not Nordic public health
      collaboration.

PMID- 26311808
TI  - Higher Plasma Phospholipid n-3 PUFAs, but Lower n-6 PUFAs, Are Associated with
      Lower Pulse Wave Velocity among Older Adults.
AB  - BACKGROUND: Higher intake of polyunsaturated fatty acids (PUFAs) and higher
      circulating PUFAs are associated with lower cardiovascular disease (CVD) risk.
      The positive influence of PUFAs might be via lowering arterial stiffness,
      resulting in a better CVD risk profile; however, studies investigating
      circulating PUFAs in relation to arterial stiffness in a general population are
      limited. OBJECTIVE: We investigated the associations of plasma phospholipid n-3
      (omega-3) and n-6 PUFAs and fish oil intake with arterial stiffness. METHODS: We
      used data from a subgroup of the Age, Gene/Environment Susceptibility-Reykjavik
      (AGES-Reykjavik) Study (n = 501, 75.0 +/- 4.96 y, 46% men), a population-based
      study of community-dwelling older adults. Plasma phospholipid PUFAs were measured
      by GC at baseline, and fish oil intake was assessed at 3 time points: early life
      (ages 14-19 y), midlife (ages 40-50 y), and late life (ages 66-96 y, AGES
      Reykjavik baseline) with the use of a validated food-frequency questionnaire.
      Arterial stiffness was determined as carotid-femoral pulse wave velocity (cf-PWV)
      with the use of an electrocardiogram after a mean follow-up of 5.2 +/- 0.3 y.
      Regression coefficients (95% CIs), adjusted for demographics, follow-up time,
      risk factors, cholesterol, triglycerides, and serum vitamin D, were calculated by
      linear regression per SD increment in PUFAs. RESULTS: Plasma total n-3 PUFAs,
      eicosapentaenoic acid, and docosahexaenoic acid were associated with lower cf-PWV
      [beta (95% CI): -0.036 (-0.064, -0.008); -0.031 (-0.059, -0.003); -0.036 (-0.064,
      -0.009), respectively]. In contrast, plasma total n-6 PUFAs and linoleic acid
      were associated with higher cf-PWV [0.035 (0.009, 0.061) and 0.034 (0.008,
      0.059)]. Regular fish oil consumption at early-, mid-, and late-life was not
      associated with cf-PWV. CONCLUSIONS: Our results show a positive association
      between plasma n-6 PUFAs and arterial stiffness, and suggest that higher
      concentrations of plasma long-chain n-3 PUFAs are associated with less arterial
      stiffness and therein may be one of the mechanisms underlying the association
      between plasma n-3 PUFAs and lower CVD risk.

PMID- 26311809
TI  - Fecal Microbial Community Structure Is Stable over Time and Related to Variation
      in Macronutrient and Micronutrient Intakes in Lactating Women.
AB  - BACKGROUND: The fecal microbiota has been characterized in some adult
      populations, but little is known about its community structure during lactation.
      OBJECTIVES: We characterized the maternal fecal microbiome during lactation and
      explored possible mediating factors such as nutrition. METHODS: Fecal samples
      were collected from 20 lactating women from 2 d to 6 mo postpartum, and bacterial
      taxa were characterized with the use of high-throughput sequencing. Bacterial
      community structure (at each taxonomic level) and relations between bacterial
      taxa and environmental and dietary variables were visualized and analyzed with
      the use of stacked bar charts, principal component analysis, and multivariate
      analyses such as nonmetric multidimensional scaling and canonical correlation
      analysis. RESULTS: Complex bacterial community structure was somewhat similar to
      those previously published for other adult populations (although there were some
      notable differences), and there were no clear associations with time postpartum
      or anthropometric or environmental variables. However, Spearman rank correlations
      suggested that increased intake of pantothenic acid, riboflavin, vitamin B-6, and
      vitamin B-12 were related to increased relative abundance of Prevotella (r =
      0.45, 0.39, 0.34, and 0.24, respectively; P <= 0.01) and decreased relative
      abundance of Bacteroides (r = -0.55, -0.46, -0.32, and -0.35, respectively; P <=
      0.01). Intakes of copper, magnesium, manganese, and molybdenum were positively
      associated with Firmicutes (r = 0.33, 0.38, 0.44, and 0.51, respectively; P <=
      0.01) and negatively associated with Bacteroidetes (r = -0.38, -0.44, -0.48, and 
      0.53, respectively; P <= 0.01). Overall, data consistently suggest that increased
      consumption of a more nutrient- and calorie-rich diet was positively associated
      with relative abundance of Firmicutes. CONCLUSIONS: The fecal microbiome of
      lactating women is relatively stable in the postpartum period and somewhat
      similar to that of other adult populations. Variation in dietary constituents may
      be related to that of relative abundance of individual bacterial taxa. Controlled
      dietary intervention studies will be required to determine whether these
      associations are causal in nature.

PMID- 26311810
TI  - Low-Dose Creatine Supplementation Lowers Plasma Guanidinoacetate, but Not Plasma
      Homocysteine, in a Double-Blind, Randomized, Placebo-Controlled Trial.
AB  - BACKGROUND: Creatine synthesis from guanidinoacetate consumes ~50% of s
      adenosylmethionine (SAM)-derived methyl groups, accounting for an equivalent
      proportion of s-adenosylhomocysteine (SAH) and total homocysteine (tHcys)
      synthesis. Dietary creatine inhibits the synthesis of guanidinoacetate, thereby
      lowering plasma tHcys in rats. OBJECTIVE: We tested the hypotheses that creatine
      supplementation lowers plasma guanidinoacetate, increases blood SAM, lowers blood
      SAH, and lowers plasma tHcys. METHODS: Bangladeshi adults were randomly assigned
      to receive 1 of 4 treatments for 12 wk: placebo (n = 101), 3 g/d creatine (Cr; n
      = 101), 400 MUg/d folic acid (FA; n = 153), or 3 g/d creatine plus 400 MUg/d
      folic acid (Cr+FA; n = 103). The outcomes of plasma guanidinoacetate and tHcys,
      as well as whole blood SAM and SAH, were analyzed at baseline and week 12 by
      HPLC. Treatment effects of creatine supplementation were examined with the use of
      the group comparisons of Cr vs. placebo and Cr+FA vs. FA. RESULTS: Plasma
      guanidinoacetate declined by 10.6% (95% CI: 4.9, 15.9) in the Cr group while
      increasing nonsignificantly in the placebo group (3.7%; 95% CI: -0.8, 8.5)
      (Pgroup difference = 0.0002). Similarly, plasma guanidinoacetate declined by 9.0%
      (95% CI: 3.4, 14.2) in the Cr+FA group while increasing in the FA group (7.0%;
      95% CI: 2.0, 12.2) (Pgroup difference < 0.0001). Plasma tHcys declined by 23.4%
      (95% CI: 19.5, 27.1) and 21.0% (95% CI: 16.4, 25.2) in the FA and Cr+FA groups,
      respectively (Pgroup difference = 0.41), with no significant changes in the
      placebo or Cr groups (Pgroup difference = 0.35). A decrease in guanidinoacetate
      over time was associated with a decrease in tHcys over time in the Cr+FA group
      (beta = 0.30; 95% CI: 0.17, 0.43; P < 0.0001). CONCLUSIONS: Our findings indicate
      that whereas creatine supplementation downregulates endogenous creatine
      synthesis, this may not on average lower plasma tHcys in humans. However, tHcys
      did decrease in those participants who experienced a decline in plasma
      guanidinoacetate while receiving creatine plus folic acid supplementation. This
      trial was registered at clinicaltrials.gov as NCT01050556.

PMID- 26311811
TI  - Dietary Whey and Casein Differentially Affect Energy Balance, Gut Hormones,
      Glucose Metabolism, and Taste Preference in Diet-Induced Obese Rats.
AB  - BACKGROUND: Dietary whey and casein proteins decrease food intake and body weight
      and improve glycemic control; however, little is known about the underlying
      mechanisms. OBJECTIVE: We determined the effects of dietary whey, casein, and a
      combination of the 2 on energy balance, hormones, glucose metabolism, and taste
      preference in rats. METHODS: In Expt. 1, Obesity Prone CD (OP-CD) rats were fed a
      high-fat control diet (33% fat energy) for 8 wk, and then randomly assigned to 4
      isocaloric dietary treatments (n = 12/group): the control treatment (CO; 14%
      protein energy from egg white), the whey treatment (WH; 26% whey + 14% egg
      white), the casein treatment (CA; 26% casein + 14% egg white), or the whey plus
      casein treatment (WHCA; 13% whey + 13% casein + 14% egg white) for 28 d.
      Measurements included food intake, energy expenditure, body composition,
      metabolic hormones, glucose tolerance and key tissue markers of glucose and
      energy metabolism. In Expt. 2, naive OP-CD rats were randomly assigned to 3
      groups (n = 8/group). During an 8 d conditioning period, each group received on
      alternate days either the CO or WH, CO or CA, or CO or WHCA. Subsequently,
      preferences for the test diets were assessed on 2 consecutive days with food
      intake measurements at regular intervals. RESULTS: In Expt. 1, food intake was
      decreased by 17-37% for the first 14 d in the WH and CA rats, and by 18-34% only
      for the first 4 d in the WHCA compared with the CO rats. Fat mass decreased by 21
      28% for the WH rats and 17-33% for the CA rats from day 14 onward, but by 30%
      only on day 28 in WHCA rats, relative to CO rats. Thus, food intake, body weight,
      and fat mass decreased more rapidly in WH and CA rats than in WHCA rats. Energy
      expenditure in WH rats decreased for the first 4 d compared with CA and WHCA
      rats, and for the first 7 d compared with the CO rats. Circulating leptin,
      glucose-dependent insulinotropic polypeptide, interleukin 6, and glucose
      concentrations were lower in WH, CA, and WHCA rats than in CO rats. Plasma
      glucagon-like peptide 1 concentrations were greater in WH than in CA or WHCA
      rats. The improvements in glucose tolerance were greater in WH than in WHCA rats.
      The plasma membrane glucose transporter 4 (GLUT4)-to-total GLUT4 ratio in
      skeletal muscle was greater in CA and WHCA rats than in CO rats; other markers of
      glucose and energy metabolism in the adipose and cardiac tissues did not differ.
      In Expt. 2, during 4 conditioning trials, daily food intake was decreased in WH,
      CA, and WHCA rats by 26-37%, 30-43%, and 23-33%, respectively, compared with CO
      rats. Preferences for WH and CA rats were 45% and 31% lower, respectively, than
      those for CO rats, but that for WHCA rats did not differ. CONCLUSION: Together,
      these data demonstrate that in obese rats, whey, casein, and their combination
      improve energy balance through differential effects on food intake, taste
      preference, energy expenditure, glucose tolerance, and gut hormone secretion.

PMID- 26311812
TI  - Polymer micelle formulations of proteasome inhibitor carfilzomib for improved
      metabolic stability and anticancer efficacy in human multiple myeloma and lung
      cancer cell lines.
AB  - Carfilzomib (CFZ) is a second-generation proteasome inhibitor drug approved for
      the treatment of multiple myeloma. Contrary to its excellent antimyeloma
      activity, CFZ has shown only limited efficacy in patients with solid
      malignancies. This lack of efficacy has been attributed in part to rapid
      degradation of CFZ in the body, possibly hindering the ability of CFZ to access
      the proteasome target in solid tumors. We hypothesized that polymer micelles, a
      currently Food and Drug Administration-approved nanoparticle drug delivery
      formulation, may protect CFZ from metabolic degradation and thus expand the
      clinical utility of the drug as an anticancer agent. To test our hypothesis, we
      prepared CFZ-entrapped polymer micelle particles with various compositions and
      drug release profiles and examined the extent of the CFZ metabolism in vitro
      using mouse liver homogenates. We also assessed the cytotoxic activities of the
      CFZ-entrapped micelle formulations in human cancer cell lines derived from B
      lymphocytes (RPMI-8226) and the lung (H460). Our data indicated that polymer
      micelle-based formulations can improve metabolic stability and cytotoxic effects
      of CFZ compared with free CFZ in human cancer cell lines tested. Taken together,
      these results suggest that polymer micelles may have potential as a delivery
      system for CFZ with an extended therapeutic utility for nonhematologic
      malignancies in the future. 

PMID- 26311814
TI  - Medication beliefs mediate the association between medical mistrust and
      antiretroviral adherence among African Americans living with HIV/AIDS.
AB  - Medical mistrust is a significant barrier to medication adherence among African
      Americans living with HIV. In this study 380 African American people receiving
      antiretroviral therapy (ART) in a southern US city completed computerized
      measures at a community-based research site. Multiple mediation modeling showed
      that medical provider mistrust was associated with medication beliefs and ART
      adherence. Also, medication beliefs predicted adherence. The indirect effects of
      medical mistrust on adherence via medication beliefs was significant; the
      indirect effect was significant for medication concerns beliefs, but not
      medication necessity beliefs. Medication concerns beliefs therefore mediate the
      association between medical mistrust and ART adherence.

PMID- 26311813
TI  - Altered protein S-glutathionylation identifies a potential mechanism of
      resistance to acetaminophen-induced hepatotoxicity.
AB  - Acetaminophen (APAP) is the most commonly used over-the-counter analgesic.
      However, hepatotoxicity induced by APAP is a major clinical issue, and the
      factors that define sensitivity to APAP remain unclear. We have previously
      demonstrated that mice nulled for glutathione S-transferase Pi (GSTP) are
      resistant to APAP-induced hepatotoxicity. This study aims to exploit this
      difference to delineate pathways of importance in APAP toxicity. We used mice
      nulled for GSTP and heme oxygenase-1 oxidative stress reporter mice, together
      with a novel nanoflow liquid chromatography-tandem mass spectrometry methodology
      to investigate the role of oxidative stress, cell signaling, and protein S
      glutathionylation in APAP hepatotoxicity. We provide evidence that the
      sensitivity difference between wild-type and Gstp1/2(-/-) mice is unrelated to
      the ability of APAP to induce oxidative stress, despite observing significant
      increases in c-Jun N-terminal kinase and extracellular signal-regulated kinase
      phosphorylation in wild-type mice. The major difference in response to APAP was
      in the levels of protein S-glutathionylation: Gstp1/2(-/-) mice exhibited a
      significant increase in the number of S-glutathionylated proteins compared with
      wild-type animals. Remarkably, these S-glutathionylated proteins are involved in
      oxidative phosphorylation, respiratory complexes, drug metabolism, and
      mitochondrial apoptosis. Furthermore, we found that S-glutathionylation of the
      rate-limiting glutathione-synthesizing enzyme, glutamate cysteine ligase, was
      markedly increased in Gstp1/2(-/-) mice in response to APAP. The data demonstrate
      that S-glutathionylation provides an adaptive response to APAP and, as a
      consequence, suggest that this is an important determinant in APAP
      hepatotoxicity. This work identifies potential novel avenues associated with cell
      survival for the treatment of chemical-induced hepatotoxicity. 

PMID- 26311815
TI  - The fear of dying and occurrence of posttraumatic stress symptoms after an acute
      coronary syndrome: A prospective observational study.
AB  - The purpose of the study was to investigate whether experiencing fear of dying
      after acute coronary syndrome predicts later posttraumatic stress symptoms. We
      enrolled 90 patients hospitalized with main diagnosis of acute coronary syndrome
      and assessed baseline characteristics. One month after discharge, we collected
      the Posttraumatic Stress Scale. A total of 24 patients (26.7%) developed
      posttraumatic stress symptoms 1 month after the acute coronary syndrome event.
      Patients with posttraumatic stress symptoms reported significantly greater fear
      of dying, helplessness, avoidance-focused coping, and severe anxiety. In our
      prospective study, fear of dying was associated with occurrence of posttraumatic
      stress symptoms in patients hospitalized with acute coronary syndrome.

PMID- 26311816
TI  - The importance of health(ism): A focus group study of lesbian, gay, bisexual,
      pansexual, queer and transgender individuals' understandings of health.
AB  - This study investigated understandings of health among lesbian, gay, bisexual,
      pansexual, queer and/or transgender people, who are under-represented in
      research. The study involved 12 focus groups in Aotearoa/New Zealand with 47
      participants who identified as lesbian, gay, bisexual, pansexual, queer and/or
      transgender and responded to an advert inviting participants without chronic
      illnesses. Three themes were inductively formulated: health is important because
      education and protection efforts are seen as required to preserve health, health
      is seen as holistic, and contextual factors are seen as creating health risks.
      These findings provide insights into how lesbian, gay, bisexual, pansexual, queer
      and/or transgender people's understandings of health draw upon notions of
      healthism.

PMID- 26311817
TI  - Eating tasty foods to cope, enhance reward, socialize or conform: What other
      psychological characteristics describe each of these motives?
AB  - Psychological characteristics associated with eating motives of the Palatable
      Eating Motives Scale (PEMS) were identified in 192 undergraduates. Coping was
      characterized by greater BMI, emotion-triggered eating, and eating concern and
      also by binge-eating and perceived stress reactivity in females. Reward
      Enhancement was characterized by greater BMI, anxiety- and depression-eating in
      females and by anger/frustration-eating in males. Conformity was strongly
      characterized by binge-eating and by failure-based stress and all eating disorder
      traits in females and by anger/frustration- and anxiety-eating in males. The sex
      divergent patterns of these traits across PEMS motives highlight the
      heterogeneity of hedonic eating. The traits may also be maintaining the motives,
      hence adresseing them should improve treatments for obesity, binge-eating, and
      foster healthier coping, reward, and psychosocial interactions.

PMID- 26311818
TI  - Validation of a brief form of the Perceived Neighborhood Social Cohesion
      questionnaire.
AB  - The aim of this study was the validation of a brief form of the Perceived
      Neighborhood Social Cohesion questionnaire using data from 5065 men from the
      "Cohort Study on Substance-Use Risk Factors." A 9-item scale covering three
      factors was proposed. Excellent indices of internal consistency were measured
      (alpha = .93). The confirmatory factor analyses resulted in acceptable fit
      indices supporting measurement invariance across French and German forms.
      Significant correlations were found between the brief form of the Perceived
      Neighborhood Social Cohesion questionnaire, and satisfaction and self-reported
      health, providing evidence of the concurrent validity of the scale. Perceived
      neighborhood social cohesion, and depression and suicide attempts were negatively
      associated, sustaining the protective effect of perceived social cohesion.

PMID- 26311819
TI  - An improved procedure for estimation of malignant breast cancer prevalence using
      partially rank ordered set samples with multiple concomitants.
AB  - Rank-based sampling designs are widely used in situations where measuring the
      variable of interest is costly but a small number of sampling units (set) can be
      easily ranked prior to taking the final measurements on them and this can be done
      at little cost. When the variable of interest is binary, a common approach for
      ranking the sampling units is to estimate the probabilities of success through a
      logistic regression model. However, this requires training samples for model
      fitting. Also, in this approach once a sampling unit has been measured, the extra
      rank information obtained in the ranking process is not used further in the
      estimation process. To address these issues, in this paper, we propose to use the
      partially rank-ordered set sampling design with multiple concomitants. In this
      approach, instead of fitting a logistic regression model, a soft ranking
      technique is employed to obtain a vector of weights for each measured unit that
      represents the probability or the degree of belief associated with its rank among
      a small set of sampling units. We construct an estimator which combines the rank
      information and the observed partially rank-ordered set measurements themselves.
      The proposed methodology is applied to a breast cancer study to estimate the
      proportion of patients with malignant (cancerous) breast tumours in a given
      population. Through extensive numerical studies, the performance of the estimator
      is evaluated under various concomitants with different ranking potentials (i.e.
      good, intermediate and bad) and tie structures among the ranks. We show that the
      precision of the partially rank-ordered set estimator is better than its
      counterparts under simple random sampling and ranked set sampling designs and,
      hence, the sample size required to achieve a desired precision is reduced.

PMID- 26311820
TI  - Validating self-reported mobile phone use in adults using a newly developed
      smartphone application.
AB  - OBJECTIVE: Interpretation of epidemiological studies on health effects from
      mobile phone use is hindered by uncertainties in the exposure assessment. We used
      a newly developed smartphone application (app) to validate self-reported mobile
      phone use and behaviour among adults. METHODS: 107 participants (mean age 41.4
      years) in the Netherlands either downloaded the software app on their smartphone
      or were provided with a study smartphone for 4 weeks. The app recorded the number
      and duration of calls, text messages, data transfer, laterality and hands-free
      use. Self-reported mobile phone use was collected before using the app and after
      6 months through an interviewer-administered questionnaire. RESULTS: The
      geometric mean ratios (GMR, 95% CI) and Spearman correlations (r) of self
      reported (after 6 months) versus recorded number and duration of calls were:
      GMR=0.65 (0.53 to 0.80), r=0.53; and GMR=1.11 (0.86 to 1.42), r=0.57
      respectively. Participants held the phone on average for 86% of the total call
      time near the head. Self-reported right side users held the phone for 70.7% of
      the total call time on the right side of the head, and left side users for 66.2%
      on the left side of the head. The percentage of total call time that the use of
      hands-free devices (headset, speaker mode, Bluetooth) was recorded increased with
      increasing frequency of reported hands-free device usage. DISCUSSION: The
      observed recall errors and precision of reported laterality and hands-free use
      can be used to quantify and improve radiofrequency exposure models based on self
      reported mobile phone use.

PMID- 26311821
TI  - Waterpipe tobacco and electronic cigarette use in a southeast London adult
      sample: a cross-sectional analysis.
AB  - BACKGROUND: Waterpipe tobacco and electronic cigarettes (e-cigarettes) share
      several features: rising popularity, use of product flavourings and concerns
      about marketing to youth. We sought to compare prevalence and predictors of
      waterpipe tobacco and e-cigarette use, and explore knowledge of waterpipe tobacco
      and support for interventions. METHODS: We used convenience sampling methods to
      conduct a cross-sectional survey among adults in the ethnically diverse southeast
      London area. Multivariate logistic regression identified predictors of waterpipe
      and e-cigarette use. Predictor variables were age, gender, ethnicity and current
      (past 30-day) cigarette use. RESULTS: Of 1176 respondents (23.0% aged 25-34
      years, 56.0% male, 57.4% white ethnicity and 30.4% current cigarette smokers),
      31.0% had tried waterpipe tobacco and 7.4% had tried e-cigarettes. Both products
      were significantly associated with younger age groups, non-white ethnicities and
      use of each other. Waterpipe tobacco was independently associated with
      consumption of cigarettes while e-cigarettes were not. Among those aware of
      waterpipe, a third answered incorrectly to knowledge questions. Among those self
      identified as coming from a traditional waterpipe-using community, two-thirds
      supported further legislative and health promotion waterpipe interventions.
      CONCLUSIONS: Waterpipe tobacco was common and more prevalent than e-cigarettes in
      this population. Interventions to prevent and control waterpipe are unlikely to
      marginalize traditional waterpipe-using communities.

PMID- 26311822
TI  - Development of a lifestyle intervention using the MRC framework for diabetes
      prevention in people with impaired glucose regulation.
AB  - BACKGROUND: We report development of a group-based lifestyle intervention, Let's
      Prevent, using the UK Medical Research Council (MRC) framework, and delivered by
      structured education to prevent type 2 diabetes mellitus (T2DM) in people with
      impaired glucose regulation (IGR) in a UK multi-ethnic population. METHODS:
      Diabetes Education and Self-Management for Ongoing and Newly Diagnosed (DESMOND)
      is the first national T2DM programme that meets National Institute for Health and
      Care Excellence criteria and formed the basis for Let's Prevent. An iterative
      cycle of initial development, piloting, collecting and collating qualitative and
      quantitative data, and reflection and modification, was used to inform and refine
      lifestyle intervention until it was fit for evaluation in a definitive randomized
      controlled trial (RCT). The programme encouraged IGR self-management using
      simple, non-technical language and visual aids. RESULTS: Qualitative and
      quantitative data suggested that intervention resulted in beneficial short-term
      behaviour change such as healthier eating patterns, improved health beliefs and
      greater participant motivation and empowerment. We also demonstrated that
      recruitment strategy and data collection methods were feasible for RCT
      implementation. CONCLUSIONS: Let's Prevent was developed following successful
      application of MRC framework criteria and the subsequent RCT will determine
      whether it is feasible, reliable and transferable from research into a real-world
      NHS primary healthcare setting. TRIAL REGISTRATION: ISRCTN80605705.

PMID- 26311823
TI  - Impact of homicide and traffic crashes on life expectancy in the largest Latin
      American country.
AB  - BACKGROUND: Brazil and Canada are on opposite poles of the spectrum for life
      expectancy in America. We identified factors underlying Brazil's lower life
      expectancy relative to Canada, with emphasis on the role of injury compared with
      other major causes. METHODS: We computed life expectancy at birth in Brazil and
      Canada in 2010 and identified the ages and causes of death responsible for the
      gap between both countries. The main outcome measure was the contribution of
      homicide and traffic accidents to the gap, compared with other causes of death.
      RESULTS: Relative to Canada, life expectancy was lower in Brazil by 8.2 years
      (men) and 5.2 years (women). Injury lowered life expectancy of men in Brazil by
      2.2 years, or more than a quarter of the gap, mainly due to homicide and traffic
      accidents between ages 20 and 64 years. Homicide and traffic accidents
      contributed more than all circulatory diseases combined. In women, circulatory
      disease was the most important cause of lower life expectancy. CONCLUSIONS: In
      2010, homicides and traffic accidents were the principal cause for short life
      expectancy of men in Brazil. Improving life expectancy in Brazil requires
      addressing the root causes of inequalities that drive illicit drug trade,
      violence and accidents.

PMID- 26311828
TI  - Evaluation of the 'Live Life Better Service', a community-based weight management
      service, for morbidly obese patients.
AB  - BACKGROUND: There is a limited evidence on the effectiveness of lifestyle
      interventions in achieving and maintaining a significant level of weight loss in
      morbidly obese patients. This study evaluated the impact on weight loss and
      psychological well-being of a community-based weight management service for
      morbidly obese patients [body mass index (BMI) >=35 with related co-morbidities
      or BMI >40] in Derbyshire county. METHODS: Five hundred and fifty-one
      participants entered the service since 2010, and 238 participants were still
      active within the service or had completed the 2-year intervention in April 2013.
      A one-group pre-post design was used to determine average weight loss (kg) and
      impact on mental health and well-being [using the validated clinical outcomes of
      routine evaluation-outcome measure (CORE-OM) questionnaire] among participants.
      Measurements were recorded at baseline, 12 weeks, 24 weeks, 1 year, 18 months and
      2 years, and significance (P <= 0.05) was determined using the paired sample t
      test. RESULTS: Statistically significant weight loss was recorded at each
      measurement point for those participants who remained engaged with the service
      (4.9 kg weight loss at 12 weeks to 18.2 kg at 2 years). There was a significant
      positive impact on psychological well-being demonstrated by CORE-OM score.
      CONCLUSIONS: Findings show clinically and statistically significant weight loss
      among participants with improvements in physical and mental health.

PMID- 26311829
TI  - A case of deep femoral artery aneurysm.
AB  - A 58-year-old man presented with paralysis and pain in the left leg, and a mass
      was found in his thigh. Because of the growth of the mass and the worsening of
      his symptoms, the patient visited our hospital. Multidetector computed tomography
      revealed a large deep femoral arterial (DFA) aneurysm. Surgical intervention was
      planned because of the large size of the aneurysm, the high risk of perforation
      and the worsening symptoms. Aneurysmectomy and revascularization of the distal
      DFA with an artificial blood vessel graft were performed. DFA aneurysms are
      extremely rare. These aneurysms have a high rate of rupture, and surgery plays an
      important role in their treatment. However, standard methods have not yet been
      established because of their rarity of DFA aneurysm. We describe a case of DFA
      aneurysm in a patient who was successfully treated with aneurysmectomy and
      revascularization with an artificial blood vessel graft. 

PMID- 26311830
TI  - Cocaine enhances HIV-1 gp120-induced lymphatic endothelial dysfunction in the
      lung.
AB  - Pulmonary complications are common in both AIDS patients and cocaine users. We
      addressed the cellular and molecular mechanisms by which HIV and cocaine may
      partner to induce their deleterious effects. Using primary lung lymphatic
      endothelial cells (L-LECs), we examined how cocaine and HIV-1 gp120, alone and
      together, modulate signaling and functional properties of L-LECs. We found that
      brief cocaine exposure activated paxillin and induced cytoskeletal rearrangement,
      while sustained exposure increased fibronectin (FN) expression, decreased Robo4
      expression, and enhanced the permeability of L-LEC monolayers. Moreover,
      incubating L-LECs with both cocaine and HIV-1 gp120 exacerbated
      hyperpermeability, significantly enhanced apoptosis, and further impaired in
      vitro wound healing as compared with cocaine alone. Our studies also suggested
      that the sigma-1 receptor (Sigma-1R) and the dopamine-4 receptor (D4R) are
      involved in cocaine-induced pathology in L-LECs. Seeking clinical correlation, we
      found that FN levels in sera and lung tissue of HIV(+) donors were significantly
      elevated as compared to HIV(-) donors. Our in vitro data demonstrate that cocaine
      and HIV-1 gp120 induce dysfunction and damage of lung lymphatics, and suggest
      that cocaine use may exacerbate pulmonary edema and fibrosis associated with HIV
      infection. Continued exploration of the interplay between cocaine and HIV should
      assist the design of therapeutics to ameliorate HIV-induced pulmonary disorders
      within the drug using population. 

PMID- 26311831
TI  - Temporal properties of inferior colliculus neurons to photonic stimulation in the
      cochlea.
AB  - Infrared neural stimulation (INS) may be beneficial in auditory prostheses
      because of its spatially selective activation of spiral ganglion neurons.
      However, the response properties of single auditory neurons to INS and the
      possible contributions of its optoacoustic effects are yet to be examined. In
      this study, the temporal properties of auditory neurons in the central nucleus of
      the inferior colliculus (ICC) of guinea pigs in response to INS were
      characterized. Spatial selectivity of INS was observed along the tonotopically
      organized ICC. Trains of laser pulses and trains of acoustic clicks were used to
      evoke single unit responses in ICC of normal hearing animals. In response to INS,
      ICC neurons showed lower limiting rates, longer latencies, and lower firing
      efficiencies. In deaf animals, ICC neurons could still be stimulated by INS while
      unresponsive to acoustic stimulation. The site and spatial selectivity of INS
      both likely shaped the temporal properties of ICC neurons. 

PMID- 26311832
TI  - A broadband acoustic stimulus is more likely than a pure tone to elicit a startle
      reflex and prepared movements.
AB  - A loud acoustic stimulus that elicits a startle reflex has long been used to
      study the neurophysiology of cortical and subcortical neural circuits. More
      recent investigations have shown that startle can act as an early trigger for
      prepared actions, suggesting a brainstem role in the preparation and initiation
      of actions. However, in order to attribute any startle-triggered voluntary
      responses to activation in subcortical structures it is necessary to measure a
      startle-related activity in these structures. The current study investigated the
      most effective stimulus for eliciting a detectible startle reflex. While more
      intense stimuli are more likely to elicit a startle reflex, the current study
      examined whether broadband noise is more likely than a pure tone to produce a
      startle at various intensities above 100 dB. Participants performed a button
      release reaction time task in response to either a 1 kHz tone or a broadband
      noise pulse with intensities ranging from 82 to 124 dB. Reaction time and EMG
      from the wrist extensors and the sternocleidomastoid (SCM) were measured. Results
      showed that startle-related SCM EMG was elicited more frequently by broadband
      noise compared to pure tones. The higher proportion of startle reflexes observed
      in SCM was associated with a higher incidence of the voluntary task being
      triggered early. A higher incidence of startle following broadband noise is
      attributed to the activation of a larger proportion of the basilar membrane;
      thus, a lower intensity broadband noise stimulus may be used to elicit startle
      reflex at a similar rate as a higher intensity pure tone. 

PMID- 26311833
TI  - Diastolic dysfunction precedes hypoxia-induced mortality in dystrophic mice.
AB  - Duchenne muscular dystrophy (DMD) is a progressive striated muscle disease that
      is characterized by skeletal muscle weakness with progressive respiratory and
      cardiac failure. Together respiratory and cardiac disease account for the
      majority of mortality in the DMD patient population. However, little is known
      regarding the effects of respiratory dysfunction on the dystrophic heart. The
      studies described here examine the effects of acute hypoxia on cardiac function.
      These studies demonstrate, for the first time, that a mouse model of DMD displays
      significant mortality following acute exposure to hypoxia. This mortality is
      characterized by a steady decline in systolic function. Retrospective analysis
      reveals that significant decreases in diastolic dysfunction, especially in the
      right ventricle, precede the decline in systolic pressure. The initial
      hemodynamic response to acute hypoxia in the mouse is similar to that observed in
      larger species, with significant increases in right ventricular afterload and
      decreases in left ventricular preload being observed. Significant increases in
      heart rate and contractility suggest hypoxia-induced activation of the
      sympathetic nervous system. These studies provide evidence that while hypoxia
      presents significant hemodynamic challenges to the dystrophic right ventricle,
      global cardiac dysfunction precedes hypoxia-induced mortality in the dystrophic
      heart. These findings are clinically relevant as the respiratory insufficiency
      evident in patients with DMD results in significant bouts of hypoxia. The results
      of these studies indicate that hypoxia may contribute to the acceleration of the
      heart disease in DMD patients. Importantly, hypoxia can be avoided through the
      use of ventilatory support. 

PMID- 26311834
TI  - Vasopressin receptors V1a and V2 are not osmosensors.
AB  - Herein, we investigated whether G protein-coupled signaling via the vasopressin
      receptors of the V1a and V2 subtypes (V1aR and V2R) could be obtained as a direct
      response to hyperosmolar challenges and/or whether hyperosmolar challenges could
      augment classical vasopressin-dependent V1aR signaling. The V1aR-dependent
      response was monitored indirectly via its effects on aquaporin 4 (AQP4) when
      heterologously expressed in Xenopus oocytes and V1aR and V2R function was
      directly monitored following heterologous expression in COS-7 cells. A tendency
      toward an osmotically induced, V1aR-mediated reduction in AQP4-dependent water
      permeability was observed, although osmotic challenges failed to mimic
      vasopressin-dependent V1aR-mediated internalization of AQP4. Direct monitoring of
      inositol phosphate (IP) production of V1aR-expressing COS-7 cells demonstrated an
      efficient vasopressin-dependent response that was, however, independent of
      hyperosmotic challenges. Similarly, the cAMP production by the V2R was unaffected
      by hyperosmotic challenges although, in contrast to the V1aR, the V2R displayed
      an ability to support alternative signaling (IP production) at higher
      concentration of vasopressin. V1aR and V2R respond directly to vasopressin
      exposure, but they do not have an ability to act as osmo- or volume sensors when
      exposed to an osmotic gradient in the absence or presence of vasopressin. 

PMID- 26311835
TI  - Activity of OP0595/beta-lactam combinations against Gram-negative bacteria with
      extended-spectrum, AmpC and carbapenem-hydrolysing beta-lactamases.
AB  - BACKGROUND: OP0595 is a diazabicyclooctane that (i) acts as a PBP2-active
      antibacterial, (ii) inhibits Class A and C beta-lactamases and (iii), like
      mecillinam, gives beta-lactamase-independent potentiation of beta-lactams
      targeting other PBPs. We tested its behaviour against beta-lactam-resistant
      Enterobacteriaceae and non-fermenters. METHODS: Organisms were UK clinical
      isolates; MICs were determined by CLSI agar dilution for OP0595 alone or combined
      at 1-4 mg/L with aztreonam, biapenem, cefepime or piperacillin. RESULTS: MICs of
      OP0595 for Escherichia coli, Enterobacter, Citrobacter and Klebsiella spp. were
      mostly 1-4 mg/L but values >4 mg/L were seen for minorities of isolates
      irrespective of other resistances, and for 50%-60% of those with ertapenem
      resistance involving porin loss plus ESBL or AmpC activity. OP0595 MICs for
      Serratia, Proteeae and non-fermenters mostly were >4 mg/L. When its MIC was <=4
      mg/L, OP0595's antibacterial activity dominated combination activity. For 'OP0595
      resistant' (MIC >4 mg/L) isolates with Class A or C beta-lactamases OP0595
      achieved strong potentiation of substrate beta-lactams, contingent on beta
      lactamase inhibition. beta-Lactamase-independent potentiation was evident with
      aztreonam, cefepime and piperacillin-less so for biapenem-for many OP0595
      resistant Enterobacteriaceae with Class B carbapenemases, which are not inhibited
      by OP0595. OP0595 acted solely as a beta-lactamase inhibitor for non-fermenters.
      CONCLUSIONS: OP0595 inhibited Enterobacteriaceae, not non-fermenters; its
      combinations had broad activity versus Enterobacteriaceae, largely contingent on
      OP0595's antibacterial activity but also on inhibition of Class A and C beta
      lactamases and on the beta-lactam-enhancer effect, which allowed activity against
      many OP0595-resistant metallo-beta-lactamase-producing Enterobacteriaceae. For
      non-fermenters OP0595 acted only as a beta-lactamase inhibitor.

PMID- 26311836
TI  - Quantifying the impact of drug combination regimens on TB treatment efficacy and
      multidrug resistance probability.
AB  - OBJECTIVES: TB patients' non-adherence to the multidrug treatment regimen is
      thought to be the main cause of the emergence of drug resistance. The purpose of
      this study was to quantify the impacts of two-drug combination regimens and non
      adherence to these regimens on treatment efficacy and drug resistance
      probability. METHODS: A drug treatment modelling strategy was developed by
      incorporating a pharmacokinetic/pharmacodynamic model into a bacterial population
      dynamic model to explore the dynamics of TB bacilli and evolution of resistance
      during multidrug combination therapy, with an emphasis on non-adherence. A Hill
      equation-based pharmacodynamic model was used to assess the bactericidal efficacy
      of single drugs and to estimate drug interactions. RESULTS: Non-adherence to the
      treatment regimen increased treatment duration by nearly 1.6- and 3.4-fold
      relative to compliance with treatment. Symptom-based intermittent treatment, a
      form of non-adherence, might lead to treatment failure and accelerated growth and
      evolution of resistant mutants, resulting in a dramatically higher probability of
      4.17 * 10(-3) (95% CI 2.10 * 10(-4)-1.28 * 10(-2)) for the emergence of MDR TB.
      Overall, determination of the optimal treatment regimen depended on the different
      types of medication adherence. CONCLUSIONS: Our model not only predicts
      evolutionary dynamics, but also quantifies treatment efficacy. More broadly, our
      model provides a quantitative framework for improving treatment protocols and
      establishing an emergence threshold of resistance that can be used to prevent
      drug resistance.

PMID- 26311837
TI  - Switching to anidulafungin from caspofungin in cancer patients in the setting of
      liver dysfunction is associated with improvement of liver function tests.
AB  - BACKGROUND: Anidulafungin does not undergo hepatic metabolism like the other
      echinocandins. Therefore, there is a perception that anidulafungin may be less
      hepatotoxic or less likely to exacerbate existing liver damage. This has not been
      substantiated in the literature. METHODS: We retrospectively reviewed all cancer
      patients in whom anidulafungin treatment was immediately preceded by treatment
      with caspofungin and there existed clinical or laboratory evidence of hepatic
      damage or dysfunction at M. D. Anderson Cancer Center from January 2010 to
      December 2013. RESULTS: Sixty-one patients were included in the study. Most
      patients had haematological malignancies (58, 95%), and the patients were
      administered hepatotoxic agents such as chemotherapeutic agents (47, 77%) and
      other medications (38, 62%) simultaneously. There were significant decreases in
      AST and ALT (P < 0.029 and P < 0.0017, respectively) between two timepoints
      (switch from caspofungin to anidulafungin and end of anidulafungin therapy). The
      median changes in AST, ALT and total bilirubin during anidulafungin therapy were 
      43 IU/L, -25 IU/L and -0.15 mg/dL, respectively. Over 70% of patients had
      favourable changes in hepatic enzymes or function, and values were stable and
      decreased at the end of anidulafungin therapy. On average, the percentage of
      patients with laboratory results meeting common terminology criteria for adverse
      events (CTCAE) grade >=2 at the time of switching to anidulafungin was decreased
      at the end of treatment. CONCLUSIONS: Median serum values and trajectory of
      hepatic enzymes and hepatotoxicity usually decreased after switching to
      anidulafungin treatment in patients with abnormal liver function tests.
      Anidulafungin could be useful in the management of cancer patients with
      hepatotoxicity occurring during caspofungin therapy.

PMID- 26311838
TI  - Loss of LPS is involved in the virulence and resistance to colistin of colistin
      resistant Acinetobacter nosocomialis mutants selected in vitro.
AB  - OBJECTIVES: Acinetobacter nosocomialis has increasingly been reported as an
      opportunistic pathogen causing nosocomial infections. Although it is more
      susceptible to all antimicrobial agents than Acinetobacter baumannii, MDR
      clinical isolates have also been described. In addition, several studies have
      shown a high percentage of resistance to colistin. Therefore, in the present
      study we investigated the mechanism of resistance to colistin in this
      microorganism. METHODS: Colistin-resistant strains were selected from the
      original colistin-susceptible A. nosocomialis strain following multi-step mutant
      selection. Comparative genomic and proteomic analyses of both colistin
      susceptible and colistin-resistant A. nosocomialis strains were performed. In
      addition, virulence was investigated using the Caenorhabditis elegans assay.
      RESULTS: The colistin-resistant mutants selected showed a lower resistance
      profile for other types of antibacterial agents together with a significant
      decrease in virulence. The LT50 (i.e. time required to kill 50% of the nematodes)
      for the colistin-susceptible strain (WT) was 7 days compared with 9 days for the
      colistin-resistant strain (256) (P < 0.0001). In the genomic studies, several
      mutations were observed in the lpxD genes, leading to the loss of LPS in the
      colistin-resistant strains. The proteomic studies showed several up- and down
      regulated proteins that may be involved in colistin resistance or in a decrease
      in the resistance profile for several antibiotics. CONCLUSIONS: This study shows
      that the mechanism of resistance to colistin by A. nosocomialis is mainly
      associated with the loss of LPS due to mutations in the lpxD gene, although
      changes in the expression of some proteins cannot be ruled out. In addition, the
      acquisition of colistin resistance is related to a decrease in virulence.

PMID- 26311839
TI  - Mutation profiling for detection of isoniazid resistance in Mycobacterium
      tuberculosis clinical isolates.
AB  - OBJECTIVES: Progress in the detection of drug-resistant TB has been underpinned
      by the development and implementation of new, reliable and rapid diagnostic
      tools. These rely mostly on the detection of specific mutations conferring
      resistance to anti-TB drugs. The aim of this study was to search for mutations
      associated with isoniazid resistance among Mycobacterium tuberculosis clinical
      isolates. METHODS: A collection of 150 M. tuberculosis strains, including 50 MDR,
      50 isoniazid-monoresistant and 50 pan-susceptible strains, was used. For all the
      strains, seven structural genes (katG, inhA, ahpC, kasA, ndh, nat and mshA) and
      two regulatory regions (mabA-inhA promoter and oxyR-ahpC intergenic region) were
      PCR amplified and sequenced in their entirety. RESULTS: Sixty-six distinct
      mutations were detected at all nine loci investigated, accounting for 109 (72.7%)
      of the strains tested. The number of strains with any mutation among the MDR,
      isoniazid-monoresistant and pan-susceptible groups was 49 (98%), 37 (74%) and 23
      (46%), respectively. Mutations in the katG gene predominated, with 29 different
      types distributed among 46 (92%) MDR, 31 (62%) isoniazid-monoresistant and 2 (4%)
      pan-susceptible strains. Twenty-nine and 19 mutations were found exclusively in
      MDR and isoniazid-monoresistant strains, respectively. CONCLUSIONS: This study
      revealed 17 mutations, previously unreported, that might be of potential use as
      new surrogate markers of isoniazid resistance. Their diagnostic accuracy needs to
      be confirmed on larger strain samples and from different geographical settings.
      For isoniazid resistance detection, molecular approaches should still be a
      complement to rather than a replacement for conventional drug susceptibility
      testing. This is supported by the lack of mutations in any of the nine genetic
      loci investigated in 18 isoniazid-resistant strains from this study.

PMID- 26311840
TI  - Combination of Candida biomarkers in patients receiving empirical antifungal
      therapy in a Spanish tertiary hospital: a potential role in reducing the duration
      of treatment.
AB  - OBJECTIVES: Initiation of empirical antifungal therapy for invasive candidiasis
      (IC) is usually based on clinical suspicion. Serological biomarkers have not yet
      been studied as a means of ruling out IC. We evaluated the potential role of two
      combined biomarkers in stopping unnecessary antifungals in patients at risk of IC
      in the ICU and in other wards. METHODS: This was a prospective observational
      study including adults starting empirical antifungal treatment for suspected IC,
      at Gregorio Maranon Hospital, Madrid (Spain). Patients were stratified according
      to admission department (ICU or other wards) and final diagnosis (no IC or proven
      or probable IC). Type of candidiasis (candidaemia or deep-seated candidiasis) was
      also considered. The Candida albicans germ tube antibody (CAGTA) test and the
      beta-d-glucan (BDG) test were performed on serum samples collected by
      venepuncture on days 0, 3 and 5 after starting empirical antifungal therapy.
      RESULTS: Sixty-three ICU patients and 37 non-ICU patients were included. High
      risk gastrointestinal surgery and sepsis in non-surgical patients were the main
      indications for empirical treatment (30% each). Patients had no IC (58%), proven
      IC (30%) or probable IC (12%). Overall, sensitivity and negative predictive value
      of the combination of both the CAGTA test and the BDG test were 97% for the
      entire population. The best performance was observed in ICU patients (sensitivity
      and negative predictive value of 100%). Among patients without IC, all biomarkers
      were negative in 31 patients. CONCLUSIONS: Serial determination of CAGTA/BDG
      during empirical antifungal therapy has a high sensitivity and negative
      predictive value. If properly confirmed, this strategy could be used to
      discontinue antifungal treatment in at least 31% of patients as a complementary
      tool in antifungal stewardship programmes.

PMID- 26311841
TI  - Growth in nurse prescribing of antibiotics: the Scottish experience 2007-13.
AB  - OBJECTIVES: The objective of this study was to retrospectively analyse patterns
      of primary care antibiotic prescribing by nurse prescribers in Scotland. METHODS:
      Data on dispensed antibiotic prescriptions written by nurse prescribers in 2007
      13 were obtained from the Prescribing Information System, a database of all NHS
      prescriptions dispensed in Scotland. RESULTS: Since 2007, there has been a steady
      increase in the volume of antibiotic prescribing in primary care undertaken by
      nurse prescribers. There was considerable variability in the frequency of
      antibiotic prescribing among nurses and across NHS regions. Since 2007, an
      increasing proportion of antibiotics prescribed by nurses are those recommended
      for first-line empirical treatment of infection, with a reduction in the
      proportion of broader-spectrum agents. Other measures of prescribing quality
      (duration of treatment of adult females with urinary tract infection and use of
      recommended doses) have improved since 2007. CONCLUSIONS: This paper is the
      first, to our knowledge, to present an analysis of data on antibiotic prescribing
      in primary care by nurse prescribers. Inappropriate prescribing is a problem and,
      given the impact that antibiotic prescribing has on antimicrobial resistance, it
      is important that the prescribing behaviour of nurses is explored. This is
      especially significant as this is a growing body of prescribers who predominately
      work in the community, where the majority of antibiotics are prescribed. This
      analysis showed that practice varies across NHS regions and between prescribers
      and although more information is needed to establish whether nurse prescribers
      are prescribing appropriately, some quality indicators may suggest that they are
      following best practice.

PMID- 26311842
TI  - Gradual increase in antibiotic concentration affects persistence of Klebsiella
      pneumoniae.
AB  - OBJECTIVES: Sublethal bactericidal antibiotics promote the formation of multidrug
      tolerant persisters. Clinically, serum drug concentration increases gradually and
      reaches the peak level with high killing efficiency some time after
      administration. This study aimed to investigate if the initial low antibiotic
      concentration would promote persister formation in Klebsiella pneumoniae, an
      increasingly important nosocomial pathogen. METHODS: Time-dependent killings of
      K. pneumoniae by different types of bactericidal antibiotics were conducted to
      determine the existence of multidrug-tolerant K. pneumoniae persisters. Killing
      experiments with antibiotic gradient feeding were then conducted for a K.
      pneumoniae laboratory strain (ATCC 10031) and a clinical isolate (YWSCU-03) by
      adding antibiotics step by step until the drug peak serum concentration was
      attained. RESULTS: Multidrug-tolerant persisters indeed existed in K. pneumoniae
      and the persistence decreased with increasing drug concentrations or prolonged
      treatments. Antibiotic gradient feeding, to simulate a gradual increase in serum
      drug concentration, not only significantly elevated the persistence of ATCC 10031
      and YWSCU-03, but also increased the frequency of drug-resistant mutant formation
      in YWSCU-03. CONCLUSIONS: After administration, the initial low serum drug
      concentration could promote the formation of multidrug-tolerant bacterial
      persisters, which could survive the lethal drug concentrations attained later and
      potentially render the antibiotic treatment fruitless. Therefore, antibiotic
      treatments should be based on the comprehensive analysis of, not only drug
      pharmacokinetics, but also the synergistic effect between pharmacokinetics and
      persister formation.

PMID- 26311844
TI  - Chemical fingerprints reveal clues to identity, heterozygosity, and relatedness.

PMID- 26311843
TI  - Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir
      experienced patients infected with diverse HIV-1 clades.
AB  - OBJECTIVES: The aim of this study was to characterize the prevalence and patterns
      of genotypic integrase inhibitor (INI) resistance in relation to HIV-1 clade.
      METHODS: The cohort comprised 533 INI-naive subjects and 255 raltegravir
      recipients with viraemia who underwent integrase sequencing in routine care
      across Europe, including 134/533 (25.1%) and 46/255 (18.0%), respectively, with
      non-B clades (A, C, D, F, G, CRF01, CRF02, other CRFs, complex). RESULTS: No
      major INI resistance-associated mutations (RAMs) occurred in INI-naive subjects.
      Among raltegravir recipients with viraemia (median 3523 HIV-1 RNA copies/mL),
      113/255 (44.3%) had one or more major INI RAMs, most commonly N155H (45/255,
      17.6%), Q148H/R/K + G140S/A (35/255, 13.7%) and Y143R/C/H (12/255, 4.7%). In
      addition, four (1.6%) raltegravir recipients showed novel mutations at recognized
      resistance sites (E92A, S147I, N155D, N155Q) and novel mutations at other
      integrase positions that were statistically associated with raltegravir exposure
      (K159Q/R, I161L/M/T/V, E170A/G). Comparing subtype B with non-B clades, Q148H/R/K
      occurred in 42/209 (20.1%) versus 2/46 (4.3%) subjects (P = 0.009) and G140S/A
      occurred in 36/209 (17.2%) versus 1/46 (2.2%) subjects (P = 0.005). Intermediate-
      to high-level cross-resistance to twice-daily dolutegravir was predicted in
      40/255 (15.7%) subjects, more commonly in subtype B versus non-B clades (39/209,
      18.7% versus 1/46, 2.2%; P = 0.003). A glycine (G) to serine (S) substitution at
      integrase position 140 required one nucleotide change in subtype B and two
      nucleotide changes in all non-B clades. CONCLUSIONS: No major INI resistance
      mutations occurred in INI-naive subjects. Reduced occurrence of Q148H/R/K +
      G140S/A was seen in non-B clades versus subtype B, and was explained by the
      higher genetic barrier to the G140S mutation observed in all non-B clades
      analysed.

PMID- 26311845
TI  - Pel is a cationic exopolysaccharide that cross-links extracellular DNA in the
      Pseudomonas aeruginosa biofilm matrix.
AB  - Biofilm formation is a complex, ordered process. In the opportunistic pathogen
      Pseudomonas aeruginosa, Psl and Pel exopolysaccharides and extracellular DNA
      (eDNA) serve as structural components of the biofilm matrix. Despite intensive
      study, Pel's chemical structure and spatial localization within mature biofilms
      remain unknown. Using specialized carbohydrate chemical analyses, we unexpectedly
      found that Pel is a positively charged exopolysaccharide composed of partially
      acetylated 1->4 glycosidic linkages of N-acetylgalactosamine and N
      acetylglucosamine. Guided by the knowledge of Pel's sugar composition, we
      developed a tool for the direct visualization of Pel in biofilms by combining Pel
      specific Wisteria floribunda lectin staining with confocal microscopy. The
      results indicate that Pel cross-links eDNA in the biofilm stalk via ionic
      interactions. Our data demonstrate that the cationic charge of Pel is distinct
      from that of other known P. aeruginosa exopolysaccharides and is instrumental in
      its ability to interact with other key biofilm matrix components. 

PMID- 26311847
TI  - Evolution of coexistence in a crowded microplate well.

PMID- 26311846
TI  - Single-molecule spectroscopy reveals how calmodulin activates NO synthase by
      controlling its conformational fluctuation dynamics.
AB  - Mechanisms that regulate the nitric oxide synthase enzymes (NOS) are of interest
      in biology and medicine. Although NOS catalysis relies on domain motions, and is
      activated by calmodulin binding, the relationships are unclear. We used single
      molecule fluorescence resonance energy transfer (FRET) spectroscopy to elucidate
      the conformational states distribution and associated conformational fluctuation
      dynamics of the two electron transfer domains in a FRET dye-labeled neuronal NOS
      reductase domain, and to understand how calmodulin affects the dynamics to
      regulate catalysis. We found that calmodulin alters NOS conformational behaviors
      in several ways: It changes the distance distribution between the NOS domains,
      shortens the lifetimes of the individual conformational states, and instills
      conformational discipline by greatly narrowing the distributions of the
      conformational states and fluctuation rates. This information was specifically
      obtainable only by single-molecule spectroscopic measurements, and reveals how
      calmodulin promotes catalysis by shaping the physical and temporal conformational
      behaviors of NOS. 

PMID- 26311848
TI  - The growing importance of mitochondrial calcium in health and disease.

PMID- 26311849
TI  - In situ structural analysis of Golgi intracisternal protein arrays.
AB  - We acquired molecular-resolution structures of the Golgi within its native
      cellular environment. Vitreous Chlamydomonas cells were thinned by cryo-focused
      ion beam milling and then visualized by cryo-electron tomography. These tomograms
      revealed structures within the Golgi cisternae that have not been seen before.
      Narrow trans-Golgi lumina were spanned by asymmetric membrane-associated protein
      arrays that had ~6-nm lateral periodicity. Subtomogram averaging showed that the
      arrays may determine the narrow central spacing of the trans-Golgi cisternae
      through zipper-like interactions, thereby forcing cargo to the trans-Golgi
      periphery. Additionally, we observed dense granular aggregates within cisternae
      and intracisternal filament bundles associated with trans-Golgi buds. These
      native in situ structures provide new molecular insights into Golgi architecture
      and function. 

PMID- 26311850
TI  - Validation of a New Recombinant Antibody Fragment (rFab)-Based Homogeneous Enzyme
      Immunoassay for the Highly Specific Detection of 6-Acetylmorphine in Urine.
AB  - The detection of 6-acetylmorphine (6-AM) in urine by immunoassay methods is
      challenging due to its short half-life and its similarity in structure to many
      commonly abused opiates that are often present at very high concentrations in
      urine. Current 6-AM homogeneous enzyme immunoassays use lyophilized reagents
      because of the instability of 6-AM in water or lack of the required specificity
      due to high cross-reactivity with morphine. A new 6-AM rFab-based homogeneous
      enzyme immunoassay (HEIA) has been developed with highly improved specificity.
      Using a cutoff concentration of 10 ng/mL, morphine or morphine glucuronides did
      not produce a positive signal up to 300,000 or 1,000,000 ng/mL, respectively.
      Assay imprecision (n = 80) was less than 1.5% using four replicates per day for
      20 days over the range 0-20 ng/mL. Cross-reactivity with structurally related or
      non-related compounds was assessed at concentrations up to 1,000,000 ng/mL.
      Interferences from endogenous compounds at +/-25% cutoff were also performed at
      the concentrations ranging from 100,000 to 500,000 ng/mL. The effect of varied pH
      values on assay performance at +/-25% cutoff was investigated; no false-positive
      or false-negative results were observed between pH 4 and -11. Based on the
      analysis of 149 authentic urine samples, the accuracy of the 6-AM HEIA compared
      with LC-MS-MS was 100%. These results demonstrated that rFab can be suitable for
      traditional HEIA with desired detection sensitivity and stability. 

PMID- 26311851
TI  - CD47 Receptor Globally Regulates Metabolic Pathways That Control Resistance to
      Ionizing Radiation.
AB  - Modulating tissue responses to stress is an important therapeutic objective.
      Oxidative and genotoxic stresses caused by ionizing radiation are detrimental to
      healthy tissues but beneficial for treatment of cancer. CD47 is a signaling
      receptor for thrombospondin-1 and an attractive therapeutic target because
      blocking CD47 signaling protects normal tissues while sensitizing tumors to
      ionizing radiation. Here we utilized a metabolomic approach to define molecular
      mechanisms underlying this radioprotective activity. CD47-deficient cells and
      cd47-null mice exhibited global advantages in preserving metabolite levels after
      irradiation. Metabolic pathways required for controlling oxidative stress and
      mediating DNA repair were enhanced. Some cellular energetics pathways differed
      basally in CD47-deficient cells, and the global declines in the glycolytic and
      tricarboxylic acid cycle metabolites characteristic of normal cell and tissue
      responses to irradiation were prevented in the absence of CD47. Thus, CD47
      mediates signaling from the extracellular matrix that coordinately regulates
      basal metabolism and cytoprotective responses to radiation injury.

PMID- 26311852
TI  - Biographical Feature: Gary V. Doern, Ph.D.

PMID- 26311853
TI  - Genomic Variability of Serial Human Isolates of Salmonella enterica Serovar
      Typhimurium Associated with Prolonged Carriage.
AB  - Salmonella enterica serovar Typhimurium is an important foodborne human pathogen
      that often causes self-limiting but severe gastroenteritis. Prolonged excretion
      of S. Typhimurium after the infection can lead to secondary transmissions.
      However, little is known about within-host genomic variation in bacteria
      associated with asymptomatic shedding. Genomes of 35 longitudinal isolates of S.
      Typhimurium recovered from 11 patients (children and adults) with culture
      confirmed gastroenteritis were sequenced. There were three or four isolates
      obtained from each patient. Single nucleotide polymorphisms (SNPs) were analyzed
      in these isolates, which were recovered between 1 and 279 days after the initial
      diagnosis. Limited genomic variation (5 SNPs or fewer) was associated with short-
      and long-term carriage of S. Typhimurium. None of the isolates was shown to be
      due to reinfection. SNPs occurred randomly, and the majority of the SNPs were
      nonsynonymous. Two nonsense mutations were observed. A nonsense mutation in flhC
      rendered the isolate nonmotile, whereas the significance of a nonsense mutation
      in yihV is unknown. The estimated mutation rate is 1.49 * 10(-6) substitution per
      site per year. S. Typhimurium isolates excreted in stools following acute
      gastroenteritis in children and adults demonstrated limited genomic variability
      over time, regardless of the duration of carriage. These findings have important
      implications for the detection of possible transmission events suspected by
      public health genomic surveillance of S. Typhimurium infections. 

PMID- 26311855
TI  - Performance of Xpert MTB/RIF Assay in Diagnosis of Pleural Tuberculosis by Use of
      Pleural Fluid Samples.
AB  - Prospectively, 162 pleural fluid samples from patients with probable tuberculous
      pleural effusion were tested by the Xpert MTB/RIF assay and the Bactec MGIT-960
      culture system. Of these, 43 (26.5%) were positive in the MGIT-960 culture, and
      23 (14.2%), in the Xpert MTB/RIF assay. The sensitivity and specificity of the
      Xpert MTB/RIF compared with the MGIT-960 culture were 54.8% and 100%,
      respectively. 

PMID- 26311854
TI  - It Is Not All about Single Nucleotide Polymorphisms: Comparison of Mobile Genetic
      Elements and Deletions in Listeria monocytogenes Genomes Links Cases of Hospital
      Acquired Listeriosis to the Environmental Source.
AB  - The control of food-borne outbreaks caused by Listeria monocytogenes in humans
      relies on the timely identification of food or environmental sources and the
      differentiation of outbreak-related isolates from unrelated ones. This study
      illustrates the utility of whole-genome sequencing for examining the link between
      clinical and environmental isolates of L. monocytogenes associated with an
      outbreak of hospital-acquired listeriosis in Sydney, Australia. Comparative
      genomic analysis confirmed an epidemiological link between the three clinical and
      two environmental isolates. Single nucleotide polymorphism (SNP) analysis showed
      that only two SNPs separated the three human outbreak isolates, which differed by
      19 to 20 SNPs from the environmental isolates and 71 to >10,000 SNPs from
      sporadic L. monocytogenes isolates. The chromosomes of all human outbreak
      isolates and the two suspected environmental isolates were syntenic. In contrast
      to the genomes of background sporadic isolates, all epidemiologically linked
      isolates contained two novel prophages and a previously unreported clustered
      regularly interspaced short palindromic repeat (CRISPR)-associated (Cas) locus
      subtype sequence. The mobile genetic element (MGE) profile of these isolates was
      distinct from that of the other serotype 1/2b reference strains and sporadic
      isolates. The identification of SNPs and clonally distinctive MGEs strengthened
      evidence to distinguish outbreak-related isolates of L. monocytogenes from
      cocirculating endemic strains. 

PMID- 26311856
TI  - Diffuse Lepromatous Leprosy Due to Mycobacterium lepromatosis in Quintana Roo,
      Mexico.
AB  - A 43-year-old woman of Mayan origin from Quintana Roo, Mexico, was diagnosed with
      diffuse lepromatous leprosy. The etiologic bacillus was determined to be
      Mycobacterium lepromatosis instead of Mycobacterium leprae. This case likely
      represents the first report of this leprosy form and its agent in the
      southeastern tip of Mexico. 

PMID- 26311857
TI  - Evaluation of Performance of Two Rapid Tests for Detection of HIV-1 and -2 in
      High- and Low-Prevalence Populations in Nigeria.
AB  - The availability of reliable human immunodeficiency virus types 1 and 2 (HIV-1/2)
      rapid tests in resource-limited settings represents an important advancement in
      the accurate diagnosis of HIV infection and presents opportunities for
      implementation of effective prevention and treatment interventions among
      vulnerable populations. A study of the potential target populations for future
      HIV vaccine studies examined the prevalence of HIV infections at six selected
      sites in Nigeria and evaluated the use of two rapid diagnostic tests (RDTs) for
      HIV. The populations included market workers at sites adjacent to military
      installations and workers at highway settlements (truck stops) who may have a
      heightened risk of HIV exposure. Samples from 3,187 individuals who provided
      informed consent were tested in parallel using the Determine (DT) and Stat-Pak
      (SP) RDTs; discordant results were subjected to the Uni-Gold (UG) RDT as a
      tiebreaker. The results were compared to those of a third-generation enzyme
      immunoassay screen with confirmation of repeat reactive samples by HIV-1 Western
      blotting. One participant was HIV-2 infected, yielding positive results on both
      RDTs. Using the laboratory algorithm as a gold standard, we calculated
      sensitivities of 98.5% (confidence interval [CI], 97.1 to 99.8%) for DT and 98.1%
      (CI, 96.7 to 99.6%) for SP and specificities of 98.7% (CI, 98.3 -99.1%) for DT
      and 99.8% (CI, 99.6 to 100%) for SP. Similar results were obtained when the sites
      were stratified into those of higher HIV prevalence (9.4% to 22.8%) versus those
      of lower prevalence (3.2% to 7.3%). A parallel two-test algorithm requiring both
      DT and SP to be positive resulted in the highest sensitivity (98.1%; CI, 96.7 to
      99.6%) and specificity (99.97%; CI, 99.9 to 100%) relative to those for the
      reference laboratory algorithm. 

PMID- 26311858
TI  - Comparison of Phenotypic and Genotypic Approaches to Capsule Typing of Neisseria
      meningitidis by Use of Invasive and Carriage Isolate Collections.
AB  - Neisseria meningitidis serogroup B (MnB) is a leading cause of bacterial
      meningitis; however, MnB is most commonly associated with asymptomatic carriage
      in the nasopharyngeal cavity, as opposed to the disease state. Two vaccines are
      now licensed for the prevention of MnB disease; a possible additional benefit of
      these vaccines could be to protect against disease indirectly by disrupting
      nasopharyngeal carriage (e.g., herd protection). To investigate this possibility,
      accurate diagnostic approaches to characterize MnB carriage isolates are
      required. In contrast to invasive meningococcal disease (IMD) isolates, which can
      be readily serogrouped, carriage isolates often lack capsule expression, making
      standard phenotypic assays unsuitable for strain characterization. Several
      antibody-based methods were evaluated for their abilities to serogroup isolates
      and were compared with two genotyping methods (real-time PCR [rt-PCR] and whole
      genome sequencing [WGS]) to identify which approach would most accurately
      ascertain the polysaccharide groups associated with carriage isolates. WGS and rt
      PCR were in agreement for 99% of IMD isolates, including those with coding
      sequences for MnB, MnC, MnW, and MnY, and the phenotypic methods correctly
      identified serogroups for 69 to 98% of IMD isolates. In contrast, only 47% of
      carriage isolates were groupable by genotypic methods, due to mutations within
      the capsule operon; of the isolates identified by genotypic methods, <=43% were
      serogroupable with any of the phenotypic methods tested. These observations
      highlight the difficulties in the serogrouping and capsular genogrouping of
      meningococcal carriage isolates. Based on our findings, WGS is the most suitable
      approach for the characterization of meningococcal carriage isolates. 

PMID- 26311859
TI  - Comparison of Diagnostic Accuracy of PCR Targeting the 47-Kilodalton Protein
      Membrane Gene of Treponema pallidum and PCR Targeting the DNA Polymerase I Gene:
      Systematic Review and Meta-analysis.
AB  - Treponema pallidum PCR (Tp-PCR) testing now is recommended as a valid tool for
      the diagnosis of primary or secondary syphilis. The objectives were to
      systematically review and determine the optimal specific target gene to be used
      for Tp-PCR. Comparisons of the performance of the two main targets are tpp47 and
      polA genes were done using meta-analysis. Three electronic bibliographic
      databases, representing abstract books from five conferences specialized in
      infectious diseases from January 1990 to March 2015, were searched. Search
      keywords included ("syphilis" OR "Treponema pallidum" OR "neurosyphilis") AND
      ("PCR" OR "PCR" OR "molecular amplification"). We included diagnostic studies
      assessing the performance of Tp-PCR targeting tpp47 (tpp47-Tp-PCR) or the polA
      gene (polA-Tp-PCR) in ulcers from early syphilis. All studies were assessed
      against quality criteria using the QUADAS-2 tool. Of 37 studies identified, 62.2%
      were judged at low risk of bias or applicability. Most used the U.S. Centers for
      Disease Control and Prevention (CDC) case definitions for primary or secondary
      (early) syphilis (89.2%; n = 33); 15 (40.5%) used darkfield microscopy (DFM). We
      did not find differences in sensitivity and specificity between the two Tp-PCR
      methods in the subgroup of studies using adequate reference tests. Among studies
      using DFM as the reference test, sensitivities were 79.8% (95% confidence
      intervals [CI], 72.7 to 85.4%) and 71.4% (46.0 to 88.0%) for tpp47-Tp-PCR and
      polA-Tp-PCR (P = 0.217), respectively; respective specificities were 95.3% (93.5
      to 96.6%) and 93.7% (91.8 to 95.2%) (P = 0.304). Our findings suggest that the
      two Tp-PCR methods have similar accuracy and could be used interchangeably. 

PMID- 26311860
TI  - Screening for Intermediately Vancomycin-Susceptible and Vancomycin
      Heteroresistant Staphylococcus aureus by Use of Vancomycin-Supplemented Brain
      Heart Infusion Agar Biplates: Defining Growth Interpretation Criteria Based on
      Gold Standard Confirmation.
AB  - BHI agars supplemented with vancomycin 4 (BHI-V4) and 3 (BHI-V3) mg/liter have
      been proposed for screening vancomycin intermediately susceptible Staphylococcus
      aureus (VISA) and heteroresistant (hVISA) phenotypes, respectively, but growth
      interpretation criteria have not been established. We reviewed the growth results
      (CFU) during population analysis profile-area under the curve (PAP-AUC) of
      consecutive methicillin-resistant Staphylococcus aureus (MRSA) blood isolates,
      which were saved intermittently between 1996 and 2012. CFU counts on BHI-V4 and
      BHI-V3 plates were stratified according to PAP-AUC interpretive criteria: <0.90
      (susceptible [S-MRSA]), 0.90 to 1.3 (hVISA), and >1.3 (VISA). CFU cutoffs that
      best predict VISA and hVISA were determined with the use of receiver operating
      characteristic (ROC) curves. Mu3, Mu50, and methicillin-susceptible S. aureus
      (MSSA) controls were included. We also prospectively evaluated manufacturer-made
      BHI-V3/BHI-V4 biplates for screening of 2010-2012 isolates. The PAP-AUC of 616
      clinical samples was consistent with S-MRSA, hVISA, and VISA in 550 (89.3%), 48
      (7.8%), and 18 (2.9%) instances, respectively. For VISA screening on BHI-V4, a
      cutoff of 2 CFU/droplet provided 100% sensitivity and 97.7% specificity. To
      distinguish VISA from hVISA, a cutoff of 16 CFU provided 83.3% sensitivity and
      94.7% specificity; the specificity was lowered to 89.5% with a 12-CFU cutoff. For
      detecting hVISA/VISA on BHI-V3, a 2-CFU/droplet cutoff provided 98.5% sensitivity
      and 93.8% specificity. These results suggest that 2-CFU/droplet cutoffs on BHI-V4
      and BHI-V3 best approximate VISA and hVISA gold standard confirmation,
      respectively, with minimal overlap in samples with borderline PAP-AUC.
      Simultaneous screening for VISA/hVISA on manufacturer-made BHI-V4/BHI-V3 biplates
      is easy to standardize and may reduce the requirement for PAP-AUC confirmation. 

PMID- 26311861
TI  - Prevalence, Risk Factors, and Transmission Dynamics of Extended-Spectrum-beta
      Lactamase-Producing Enterobacteriaceae: a National Survey of Cattle Farms in
      Israel in 2013.
AB  - Our objectives were to study the prevalence, risk factors for carriage, and
      transmission dynamics of extended-spectrum-beta-lactamase (ESBL)-producing
      Enterobacteriaceae (ESBLPE) in a national survey of cattle. This was a point
      prevalence study conducted from July to October 2013 in Israel. Stool samples
      were collected from 1,226 cows in 123 sections on 40 farms of all production
      types. ESBLPE were identified in 291 samples (23.7%): 287 contained Escherichia
      coli and 4 contained Klebsiella pneumoniae. The number of ESBLPE-positive cows
      was the highest in quarantine stations and on fattening farms and was the lowest
      on pasture farms (P = 0.03). The number of ESBLPE-positive cows was the lowest in
      sections containing adult cows (age, >25 months) and highest in sections
      containing calves (age, <4 months) (P < 0.001). Infrastructure variables that
      were significant risk factors for ESBLPE carriage included crowding, a lack of
      manure cleaning, and a lack of a cooling (P < 0.001 for each), all of which were
      more common in sections containing calves. Antimicrobial prophylaxis was given
      almost exclusively to calves and was associated with a high number of ESBLPE
      carriers (P < 0.001). The 287 E. coli isolates were typed into 106 repetitive
      extragenic palindromic (REP)-PCR types and mostly harbored blaCTX-M-1 or blaCTX-M
      9 group genes. The isolates on the six farms with >=15 isolates of ESBLPE were of
      4 to 7 different REP-PCR types, with one dominant type being harbored by about
      half of the isolates. Fourteen types were identified on more than one farm, with
      only six of the farms being adjacent to each other. The prevalence of ESBLPE
      carriage is high in calves in cowsheds where the use of antimicrobial prophylaxis
      is common. ESBLPE disseminate within cowsheds mainly by clonal spread, with
      limited intercowshed transmission occurring.

PMID- 26311862
TI  - Comparison of the Carba NP, Modified Carba NP, and Updated Rosco Neo-Rapid Carb
      Kit Tests for Carbapenemase Detection.
AB  - The accurate detection of carbapenemase-producing organisms is a major challenge
      for clinical laboratories. The Carba NP test is highly accurate but inconvenient,
      as it requires frequent preparation of fresh imipenem solution. The current study
      was designed to compare the Carba NP test to two alternative tests for accuracy
      and convenience. These were a modified Carba NP test that utilized intravenous
      (i.v.) imipenem-cilastatin, which is less expensive than reference standard
      imipenem powder, and an updated version of the Rosco Neo-Rapid Carb kit, which
      does not require the preparation of imipenem solution and has a shelf life of 2
      years. The comparison included 87 isolates that produced class A carbapenemases
      (including KPC-2, -3, -4, -5, -6, and -8, NMC-A, and SME type), 40 isolates that
      produced metallo-beta-lactamases (including NDM-1, GIM-1, SPM-1, IMP-1, -2, -7, 
      8, -18, and -27, and VIM-1, -2, and -7), 11 isolates that produced OXA-48, and
      one isolate that produced OXA-181. Negative controls consisted of 50 isolates
      that produced extended-spectrum beta-lactamases (ESBLs), AmpCs (including
      hyperproducers), K1, other limited-spectrum beta-lactamases, and porin and efflux
      mutants. Each test exhibited 100% specificity and high sensitivity (Carba NP,
      100%; Rosco, 99% using modified interpretation guidelines; and modified Carba NP,
      96%). A modified approach to interpretation of the Rosco test was necessary to
      achieve the sensitivity of 99%. If the accuracy of the modified interpretation is
      confirmed, the Rosco test is an accurate and more convenient alternative to the
      Carba NP test. 

PMID- 26311863
TI  - Is Shiga Toxin-Negative Escherichia coli O157:H7 Enteropathogenic or
      Enterohemorrhagic Escherichia coli? Comprehensive Molecular Analysis Using Whole
      Genome Sequencing.
AB  - The ability of Escherichia coli O157:H7 to induce cellular damage leading to
      disease in humans is related to numerous virulence factors, most notably the stx
      gene, encoding Shiga toxin (Stx) and carried by a bacteriophage. Loss of the Stx
      encoding bacteriophage may occur during infection or culturing of the strain.
      Here, we collected stx-positive and stx-negative variants of E. coli O157:H7/NM
      (nonmotile) isolates from patients with gastrointestinal complaints. Isolates
      were characterized by whole-genome sequencing (WGS), and their virulence
      properties and phylogenetic relationship were determined. Because of the presence
      of the eae gene but lack of the bfpA gene, the stx-negative isolates were
      considered atypical enteropathogenic E. coli (aEPEC). However, they had
      phenotypic characteristics similar to those of the Shiga toxin-producing E. coli
      (STEC) isolates and belonged to the same sequence type, ST11. Furthermore, EPEC
      and STEC isolates shared similar virulence genes, the locus of enterocyte
      effacement region, and plasmids. Core genome phylogenetic analysis using a gene
      by-gene typing approach showed that the sorbitol-fermenting (SF) stx-negative
      isolates clustered together with an SF STEC isolate and that one non-sorbitol
      fermenting (NSF) stx-negative isolate clustered together with NSF STEC isolates.
      Therefore, these stx-negative isolates were thought either to have lost the Stx
      phage or to be a progenitor of STEC O157:H7/NM. As detection of STEC infections
      is often based solely on the identification of the presence of stx genes, these
      may be misdiagnosed in routine laboratories. Therefore, an improved diagnostic
      approach is required to manage identification, strategies for treatment, and
      prevention of transmission of these potentially pathogenic strains. 

PMID- 26311864
TI  - Fluoroquinolone Resistance in Salmonella and the Utility of Pefloxacin Disk
      Diffusion [corrected].
AB  - Fluoroquinolone resistance is a serious and increasingly common problem in
      Salmonella. Two companion studies in this issue of the Journal of Clinical
      Microbiology (E. Deak, R. Skov, J. A. Hindler, and R. M. Humphries, J Clin
      Microbiol 53:3405-3410, 2015, http://dx.doi.org/10.1128/JCM.01393-15; R. Skov, E.
      Matuschek, M. Sjolund-Karlsson, J. Ahman, A. Petersen, M. Stegger, M. Torpdahl,
      and G. Kahlmeter, J Clin Microbiol 53:3411-3417, 2015,
      http://dx.doi.org/10.1128/JCM.01287-15) provide data to support the use of
      pefloxacin disk diffusion as a convenient and inexpensive surrogate laboratory
      method to detect fluoroquinolone resistance in Salmonella when the direct
      measurement of fluoroquinolone MICs is not feasible [corrected]. Recently updated
      CLSI and EUCAST susceptibility breakpoints will help to optimize clinical
      outcomes and reduce the likelihood of emergent resistance.

PMID- 26311865
TI  - Clinical Characteristics, Laboratory Identification, and In Vitro Antifungal
      Susceptibility of Yarrowia (Candida) lipolytica Isolates Causing Fungemia: a
      Multicenter, Prospective Surveillance Study.
AB  - Our case series showed that uncomplicated Yarrowia lipolytica fungemia might be
      treated with catheter removal alone. The Vitek 2 YST identification (ID) card
      system, matrix-assisted laser desorption ionization-time of flight mass
      spectrometry (MALDI-TOF MS), and internal transcribed spacer and 25S nuclear
      ribosomal DNA (nrDNA) gene sequencing provided reliable identification. All
      isolates had low MICs to voriconazole, echinocandins, and amphotericin B. 

PMID- 26311866
TI  - Multiplex Molecular Panels for Diagnosis of Gastrointestinal Infection: 
      Performance, Result Interpretation, and Cost-Effectiveness.
AB  - Gastrointestinal disease is a major cause of morbidity and mortality worldwide,
      especially among young children and immunocompromised patients. Diarrhea may
      result from infection with a variety of microbial pathogens, including bacteria,
      viruses, or parasites. Historically, the diagnosis of infectious diarrhea has
      been made using microscopy, antigen tests, culture, and real-time PCR. A
      combination of these traditional tests is often required due to the inability to
      distinguish between infectious etiologies based on the clinical presentation
      alone. Recently, several multiplex molecular assays have been developed for the
      detection of gastrointestinal pathogens directly from clinical stool samples.
      These panels allow for the detection and identification of up to 20 pathogens in
      as little as 1 h. This review will focus on the multiplex molecular panels that
      have received clearance from the FDA for the diagnosis of diarrheal disease and
      will highlight issues related to test performance, result interpretation, and
      cost-effectiveness of these new molecular diagnostic tools.

PMID- 26311867
TI  - Pathogen-Associated Molecular Pattern Recognition of Hepatitis C Virus
      Transmitted/Founder Variants by RIG-I Is Dependent on U-Core Length.
AB  - Despite the introduction of direct-acting antiviral (DAA) drugs against hepatitis
      C virus (HCV), infection remains a major public health concern because DAA
      therapeutics do not prevent reinfection and patients can still progress to
      chronic liver disease. Chronic HCV infection is supported by a variety of viral
      immune evasion strategies, but, remarkably, 20% to 30% of acute infections
      spontaneously clear prior to development of adaptive immune responses, thus
      implicating innate immunity in resolving acute HCV infection. However, the virus
      host interactions regulating acute infection are unknown. Transmission of HCV
      involves one or a few transmitted/founder (T/F) variants. In infected
      hepatocytes, the retinoic acid-inducible gene I (RIG-I) protein recognizes 5'
      triphosphate (5'ppp) of the HCV RNA and a pathogen-associated molecular pattern
      (PAMP) motif located within the 3' untranslated region consisting of poly-U/UC.
      PAMP binding activates RIG-I to induce innate immune signaling and type 1
      interferon antiviral defenses. HCV poly-U/UC sequences can differ in length and
      complexity, suggesting that PAMP diversity in T/F genomes could regulate innate
      immune control of acute HCV infection. Using 14 unique poly-U/UC sequences from
      HCV T/F genomes recovered from acute-infection patients, we tested whether RIG-I
      recognition and innate immune activation correlate with PAMP sequence
      characteristics. We show that T/F variants are recognized by RIG-I in a manner
      dependent on length of the U-core motif of the poly-U/UC PAMP and are recognized
      by RIG-I to induce innate immune responses that restrict acute infection. PAMP
      recognition of T/F HCV variants by RIG-I may therefore impart innate immune
      signaling and HCV restriction to impact acute-phase-to-chronic-phase transition.
      IMPORTANCE: Recognition of nonself molecular patterns such as those seen with
      viral nucleic acids is an essential step in triggering the immune response to
      virus infection. Innate immunity is induced by hepatitis C virus infection
      through the recognition of viral RNA by the cellular RIG-I protein, where RIG-I
      recognizes a poly-uridine/cytosine motif in the viral genome. Variation within
      this motif may provide an immune evasion strategy for transmitted/founder viruses
      during acute infection. Using 14 unique poly-U/UC sequences from HCV T/F genomes
      recovered from acutely infected HCV patients, we demonstrate that RIG-I binding
      and activation of innate immunity depend primarily on the length of the uridine
      core within this motif. T/F variants found in acute infection contained longer U
      cores within the motif and could activate RIG-I and induce innate immune
      signaling sufficient to restrict viral infection. Thus, recognition of T/F
      variants by RIG-I could significantly impact the transition from acute to chronic
      infection.

PMID- 26311870
TI  - Knockout of cGAS and STING Rescues Virus Infection of Plasmid DNA-Transfected
      Cells.
AB  - It is well known that plasmid DNA transfection, prior to virus infection,
      negatively affects infection efficiency. Here, we show that cytosolic plasmid DNA
      activates the cGAS/STING signaling pathway, which ultimately leads to the
      induction of an antiviral state of the cells. Using a transient one-plasmid
      clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system, we
      generated cGAS/STING-knockout cells and show that these cells can be infected
      after plasmid DNA transfection as efficiently as nontransfected cells. 

PMID- 26311868
TI  - Sinorhizobium meliloti Phage PhiM9 Defines a New Group of T4 Superfamily Phages
      with Unusual Genomic Features but a Common T=16 Capsid.
AB  - Relatively little is known about the phages that infect agriculturally important
      nitrogen-fixing rhizobial bacteria. Here we report the genome and cryo-electron
      microscopy structure of the Sinorhizobium meliloti-infecting T4 superfamily phage
      PhiM9. This phage and its close relative Rhizobium phage vB_RleM_P10VF define a
      new group of T4 superfamily phages. These phages are distinctly different from
      the recently characterized cyanophage-like S. meliloti phages of the PhiM12
      group. Structurally, PhiM9 has a T=16 capsid formed from repeating units of an
      extended gp23-like subunit that assemble through interactions between one subunit
      and the adjacent E-loop insertion domain. Though genetically very distant from
      the cyanophages, the PhiM9 capsid closely resembles that of the T4 superfamily
      cyanophage Syn9. PhiM9 also has the same T=16 capsid architecture as the very
      distant phage SPO1 and the herpesviruses. Despite their overall lack of
      similarity at the genomic and structural levels, PhiM9 and S. meliloti phage
      PhiM12 have a small number of open reading frames in common that appear to encode
      structural proteins involved in interaction with the host and which may have been
      acquired by horizontal transfer. These proteins are predicted to encode tail
      baseplate proteins, tail fibers, tail fiber assembly proteins, and glycanases
      that cleave host exopolysaccharide. IMPORTANCE: Despite recent advances in the
      phylogenetic and structural characterization of bacteriophages, only a small
      number of phages of plant-symbiotic nitrogen-fixing soil bacteria have been
      studied at the molecular level. The effects of phage predation upon beneficial
      bacteria that promote plant growth remain poorly characterized. First steps in
      understanding these soil bacterium-phage dynamics are genetic, molecular, and
      structural characterizations of these groups of phages. The T4 superfamily phages
      are among the most complex phages; they have large genomes packaged within an
      icosahedral head and a long, contractile tail through which the DNA is delivered
      to host cells. This phylogenetic and structural study of S. meliloti-infecting T4
      superfamily phage PhiM9 provides new insight into the diversity of this family.
      The comparison of structure-related genes in both PhiM9 and S. meliloti-infecting
      T4 superfamily phage PhiM12, which comes from a completely different lineage of
      these phages, allows the identification of host infection-related factors.

PMID- 26311869
TI  - Mechanism of Binding to Ebola Virus Glycoprotein by the ZMapp, ZMAb, and MB-003
      Cocktail Antibodies.
AB  - Cocktails of monoclonal antibodies (MAbs) that target the surface glycoprotein
      (GP) of Ebola virus (EBOV) are effective in nonhuman primate models and have been
      used under emergency compassionate-treatment protocols in human patients.
      However, the amino acids that form the detailed binding epitopes for the MAbs in
      the ZMapp, ZMAb, and the related MB-003 cocktails have yet to be identified.
      Other binding properties that define how each MAb functionally interacts with GP
      such as affinity, epitope conservation, and epitope accessibility-also remain
      largely unknown. To help define how each MAb interacts with GP, here we used
      comprehensive alanine-scanning mutagenesis (shotgun mutagenesis), neutralization
      escape, and whole virion binding to define each MAb's specific epitope, epitope
      accessibility, epitope conservation, and apparent affinity. Each of the six
      therapeutic MAbs binds nonidentical epitopes in the GP base, glycan cap, or mucin
      like domain. Their apparent affinity, epitope complementarity, and epitope
      accessibility helps explain why MAbs 4G7 and 13C6 are more protective than 2G4
      and 1H3. The mucin-like domain MAbs 6D8 and 13F6 bind with the strongest apparent
      affinity, helping to explain their effectiveness in vivo despite their inability
      to neutralize virus. IMPORTANCE: Ebola virus disease (EVD) can be caused by four
      different filovirus family members, including Ebola virus (EBOV), which infected
      10 times more people in western Africa over the last year than all previous EVD
      outbreaks combined, with a number of cases distributed across the globe by
      travelers. Cocktails of inhibitory monoclonal antibodies (MAbs), such as ZMAb, MB
      003, and in particular ZMapp, have demonstrated in animal models some of the most
      significant therapeutic potential for treating EVD, and in 2014, 15 patients were
      treated with ZMapp or ZMAb under compassionate-use protocols. Here, we have
      defined the epitope features for the most important therapeutic MAbs against EBOV
      developed to date. Defining the epitopes and binding characteristics for these
      MAbs, as well as the commonly used reference MAb KZ52, helps explain their
      breadth of reactivity against different ebolavirus species, predict viral evasion
      against these MAbs, and design new cocktails of MAbs with improved
      complementarity.

PMID- 26311871
TI  - L Particles Transmit Viral Proteins from Herpes Simplex Virus 1-Infected Mature
      Dendritic Cells to Uninfected Bystander Cells, Inducing CD83 Downmodulation.
AB  - Mature dendritic cells (mDCs) are known as the most potent antigen-presenting
      cells (APCs) since they are also able to prime/induce naive T cells. Thus, mDCs
      play a pivotal role during the induction of antiviral immune responses.
      Remarkably, the cell surface molecule CD83, which was shown to have costimulatory
      properties, is targeted by herpes simplex virus 1 (HSV-1) for viral immune
      escape. Infection of mDCs with HSV-1 results in downmodulation of CD83, resulting
      in reduced T cell stimulation. In this study, we report that not only infected
      mDCs but also uninfected bystander cells in an infected culture show a
      significant CD83 reduction. We demonstrate that this effect is independent of
      phagocytosis and transmissible from infected to uninfected mDCs. The presence of
      specific viral proteins found in these uninfected bystander cells led to the
      hypothesis that viral proteins are transferred from infected to uninfected cells
      via L particles. These L particles are generated during lytic replication in
      parallel with full virions, called H particles. L particles contain viral
      proteins but lack the viral capsid and DNA. Therefore, these particles are not
      infectious but are able to transfer several viral proteins. Incubation of mDCs
      with L particles indeed reduced CD83 expression on uninfected bystander DCs,
      providing for the first time evidence that functional viral proteins are
      transmitted via L particles from infected mDCs to uninfected bystander cells,
      thereby inducing CD83 downmodulation. IMPORTANCE: HSV-1 has evolved a number of
      strategies to evade the host's immune system. Among others, HSV-1 infection of
      mDCs results in an inhibited T cell activation caused by degradation of CD83.
      Interestingly, CD83 is lost not only from HSV-1-infected mDCs but also from
      uninfected bystander cells. The release of so-called L particles, which contain
      several viral proteins but lack capsid and DNA, during infection is a common
      phenomenon observed among several viruses, such as human cytomegalovirus (HCMV),
      Epstein-Barr virus, and HSV-1. However, the detailed function of these particles
      is poorly understood. Here, we provide for the first time evidence that
      functional viral proteins can be transferred to uninfected bystander mDCs via L
      particles, revealing important biological functions of these particles during
      lytic replication. Therefore, the transfer of viral proteins by L particles to
      modulate uninfected bystander cells may represent an additional strategy for
      viral immune escape.

PMID- 26311872
TI  - In Vitro Evidence Supports Membrane Alanyl Aminopeptidase N as a Receptor for a
      Plant Virus in the Pea Aphid Vector.
AB  - Insect-borne plant viruses cause significant agricultural losses and jeopardize
      sustainable global food production. Although blocking plant virus transmission
      would allow for crop protection, virus receptors in insect vectors are unknown.
      Here we identify membrane alanyl aminopeptidase N (APN) as a receptor for pea
      enation mosaic virus (PEMV) coat protein (CP) in the gut of the pea aphid,
      Acyrthosiphon pisum, using a far-Western blot method. Pulldown and
      immunofluorescence binding assays and surface plasmon resonance were used to
      confirm and characterize CP-APN interaction. PEMV virions and a peptide comprised
      of PEMV CP fused to a proline-rich hinge (-P-) and green fluorescent protein (CP
      P-GFP) specifically bound to APN. Recombinant APN expressed in Sf9 cells resulted
      in internalization of CP-P-GFP, which was visualized by confocal microscopy; such
      internalization is an expected hallmark of a functional gut receptor. Finally, in
      assays with aphid gut-derived brush border membrane vesicles, binding of CP-P-GFP
      competed with binding of GBP3.1, a peptide previously demonstrated to bind to APN
      in the aphid gut and to impede PEMV uptake into the hemocoel; this finding
      supports the hypothesis that GBP3.1 and PEMV bind to and compete for the same APN
      receptor. These in vitro data combined with previously published in vivo
      experiments (S. Liu, S. Sivakumar, W. O. Sparks, W. A. Miller, and B. C. Bonning,
      Virology 401:107-116, 2010, http://dx.doi.org/10.1016/j.virol.2010.02.009)
      support the identification of APN as the first receptor in a plant virus vector.
      Knowledge of this receptor will provide for technologies based on PEMV-APN
      interaction designed to block plant virus transmission and to suppress aphid
      populations. IMPORTANCE: A significant proportion of global food production is
      lost to insect pests. Aphids, in addition to weakening plants by feeding on their
      sap, are responsible for transmitting about half of the plant viruses vectored by
      insects. Growers rely heavily on the application of chemical insecticides to
      manage both aphids and aphid-vectored plant viral disease. To increase our
      understanding of plant virus-aphid vector interaction, we provide in vitro
      evidence supporting earlier in vivo work for identification of a receptor protein
      in the aphid gut called aminopeptidase N, which is responsible for entry of the
      plant virus pea enation mosaic virus into the pea aphid vector. Enrichment of
      proteins found on the surface of the aphid gut epithelium resulted in
      identification of this first aphid gut receptor for a plant virus. This discovery
      is particularly important since the disruption of plant virus binding to such a
      receptor may enable the development of a nonchemical strategy for controlling
      aphid-vectored plant viruses to maximize food production.

PMID- 26311873
TI  - Selective Removal of FG Repeat Domains from the Nuclear Pore Complex by
      Enterovirus 2A(pro).
AB  - Enteroviruses proteolyze nuclear pore complex (NPC) proteins (Nups) during
      infection, leading to disruption of host nuclear transport pathways and
      alterations in nuclear permeability. To better understand how enteroviruses exert
      these effects on nuclear transport, the mechanisms and consequences of Nup98
      proteolysis were examined. The results indicate that Nup98 is rapidly targeted
      for degradation following enterovirus infection and that this is mediated by the
      enterovirus 2A protease (2A(pro)). Incubation of bacterially expressed or in
      vitro-translated Nup98 with 2A(pro) results in proteolytic cleavage at multiple
      sites in vitro, indicating that 2A(pro) cleaves Nup98 directly. Site-directed
      mutagenesis of putative cleavage sites identified Gly374 and Gly552 as the sites
      of 2A(pro) proteolysis in Nup98 in vitro and in infected cells. Indirect
      immunofluorescence assays using an antibody that recognizes the N terminus of
      Nup98 revealed that proteolysis releases the N-terminal FG-rich region from the
      NPC. In contrast, similar analyses using an antibody to the C terminus indicated
      that this region is retained at the nuclear rim. Nup88, a core NPC component that
      serves as a docking site for Nup98, also remains at the NPC in infected cells.
      These findings support a model whereby the selective removal of Nup FG repeat
      domains leads to increased NPC permeability and inhibition of certain transport
      pathways, while retention of structural domains maintains the overall NPC
      structure and leaves other transport pathways unaffected. IMPORTANCE:
      Enteroviruses are dependent upon host nuclear RNA binding proteins for efficient
      replication. This study examines the mechanisms responsible for alterations in
      nuclear transport in enterovirus-infected cells that lead to the cytoplasmic
      accumulation of these proteins. The results demonstrate that the enterovirus 2A
      protease directly cleaves the nuclear pore complex (NPC) protein, Nup98, at amino
      acid positions G374 and G552 both in vitro and in infected cells. Cleavage at
      these positions results in the selective removal of the FG-containing N terminus
      of Nup98 from the NPC, while the C terminus remains associated. Nup88, a core
      component of the NPC that serves as a docking site for the C terminus of Nup98,
      remains associated with the NPC in infected cells. These findings help to explain
      the alterations in permeability and nuclear transport in enterovirus-infected
      cells and how NPCs remain functional for certain trafficking pathways despite
      significant alterations to their compositions.

PMID- 26311874
TI  - Inactivation of the Human Cytomegalovirus US20 Gene Hampers Productive Viral
      Replication in Endothelial Cells.
AB  - The human cytomegalovirus (HCMV) US12 gene family includes a group of 10
      contiguous genes (US12 to US21) encoding predicted seven-transmembrane-domain
      (7TMD) proteins that are nonessential for replication within cultured
      fibroblasts. Nevertheless, inactivation of some US12 family members affects virus
      replication in other cell types; e.g., deletion of US16 or US18 abrogates virus
      growth in endothelial and epithelial cells or in human gingival tissue,
      respectively, suggesting a role for some US12 proteins in HCMV cell tropism.
      Here, we provide evidence that another member, US20, impacts the ability of a
      clinical strain of HCMV to replicate in endothelial cells. Through the use of
      recombinant HCMV encoding tagged versions of the US20 protein, we investigated
      the expression pattern, localization, and topology of the US20-encoded protein
      (pUS20). We show that pUS20 is expressed as a partially glycosylated 7TMD protein
      which accumulates late in infection in endoplasmic reticulum-derived peripheral
      structures localized outside the cytoplasmic virus assembly compartment (cVAC).
      US20-deficient mutants generated in the TR clinical strain of HCMV exhibited
      major growth defects in different types of endothelial cells, whereas they
      replicated normally in fibroblasts and epithelial cells. While the attachment and
      entry phases in endothelial cells were not significantly affected by the absence
      of US20 protein, US20-null viruses failed to replicate viral DNA and express
      representative E and L mRNAs and proteins. Taken together, these results indicate
      that US20 sustains the HCMV replication cycle at a stage subsequent to entry but
      prior to E gene expression and viral DNA synthesis in endothelial cells.
      IMPORTANCE: Human cytomegalovirus (HCMV) is a major pathogen in newborns and
      immunocompromised individuals. A hallmark of HCMV pathogenesis is its ability to
      productively replicate in an exceptionally broad range of target cells, including
      endothelial cells, which represent a key target for viral dissemination and
      replication in the host, and to contribute to both viral persistence and
      associated inflammation and vascular diseases. Replication in endothelial cells
      depends on the activities of a set of viral proteins that regulate different
      stages of the HCMV replication cycle in an endothelial cell type-specific manner
      and thereby act as determinants of viral tropism. Here, we report the requirement
      of a HCMV protein as a postentry tropism factor in endothelial cells. The
      identification and characterization of HCMV endotheliotropism-regulating proteins
      will advance our understanding of the molecular mechanisms of HCMV-related
      pathogenesis and help lead to the design of new antiviral strategies able to
      exploit these functions.

PMID- 26311875
TI  - Differences in Processing Determinants of Nonstructural Polyprotein and in the
      Sequence of Nonstructural Protein 3 Affect Neurovirulence of Semliki Forest
      Virus.
AB  - The A7(74) strain of Semliki Forest virus (SFV; genus Alphavirus) is avirulent in
      adult mice, while the L10 strain is virulent in mice of all ages. It has been
      previously demonstrated that this phenotypic difference is associated with
      nonstructural protein 3 (nsP3). Consensus clones of L10 (designated SFV6) and
      A7(74) (designated A774wt) were used to construct a panel of recombinant viruses.
      The insertion of nsP3 from A774wt into the SFV6 backbone had a minor effect on
      the virulence of the resulting recombinant virus. Conversely, insertion of nsP3
      from SFV6 into the A774wt backbone or replacement of A774wt nsP3 with two copies
      of nsP3 from SFV6 resulted in virulent viruses. Unexpectedly, duplication of nsP3
      encoding sequences also resulted in elevated levels of nsP4, revealing that nsP3
      is involved in the stabilization of nsP4. Interestingly, replacement of nsP3 of
      SFV6 with that of A774wt resulted in a virulent virus; the virulence of this
      recombinant was strongly reduced by functionally coupled substitutions for amino
      acid residues 534 (P4 position of the cleavage site between nsP1 and nsP2) and
      1052 (S4 subsite residue of nsP2 protease) in the nonstructural polyprotein.
      Pulse-chase experiments revealed that A774wt and avirulent recombinant virus were
      characterized by increased processing speed of the cleavage site between nsP1 and
      nsP2. A His534-to-Arg substitution specifically activated this cleavage, while a
      Val1052-to-Glu substitution compensated for this effect by reducing the basal
      protease activity of nsP2. These findings provide a link between nonstructural
      polyprotein processing and the virulence of SFV. IMPORTANCE: SFV infection of
      mice provides a well-characterized model to study viral encephalitis. SFV also
      serves as a model for studies of alphavirus molecular biology and host-pathogen
      interactions. Thus far, the genetic basis of different properties of SFV strains
      has been studied using molecular clones, which often contain mistakes originating
      from standard cDNA synthesis and cloning procedures. Here, for the first time,
      consensus clones of SFV strains were used to map virulence determinants. Existing
      data on the importance of nsP3 for virulent phenotypes were confirmed, another
      determinant of neurovirulence and its molecular basis was characterized, and a
      novel function of nsP3 was identified. These findings provide links between the
      molecular biology of SFV and its biological properties and significantly increase
      our understanding of the basis of alphavirus-induced pathology. In addition, the
      usefulness of consensus clones as tools for studies of alphaviruses was
      demonstrated.

PMID- 26311876
TI  - A Nucleolar Protein, Ribosomal RNA Processing 1 Homolog B (RRP1B), Enhances the
      Recruitment of Cellular mRNA in Influenza Virus Transcription.
AB  - Influenza A virus (IAV) undergoes RNA transcription by a unique capped-mRNA
      dependent transcription, which is carried out by the viral RNA-dependent RNA
      polymerase (RdRp), consisting of the viral PA, PB1, and PB2 proteins. However,
      how the viral RdRp utilizes cellular factors for virus transcription is not
      clear. Previously, we conducted a genome-wide pooled short hairpin RNA (shRNA)
      screen to identify host factors important for influenza A virus replication.
      Ribosomal RNA processing 1 homolog B (RRP1B) was identified as one of the
      candidates. RRP1B is a nucleolar protein involved in ribosomal biogenesis. Upon
      IAV infection, part of RRP1B was translocated from the nucleolus to the
      nucleoplasm, where viral RNA synthesis likely takes place. The depletion of RRP1B
      significantly reduced IAV mRNA transcription in a minireplicon assay and in virus
      infected cells. Furthermore, we showed that RRP1B interacted with PB1 and PB2 of
      the RdRp and formed a coimmunoprecipitable complex with RdRp. The depletion of
      RRP1B reduced the amount of capped mRNA in the RdRp complex. Taken together,
      these findings indicate that RRP1B is a host factor essential for IAV
      transcription and provide a target for new antivirals. IMPORTANCE: Influenza
      virus is an important human pathogen that causes significant morbidity and
      mortality and threatens the human population with epidemics and pandemics every
      year. Due to the high mutation rate of the virus, antiviral drugs targeting viral
      proteins might ultimately lose their effectiveness. An alternative strategy that
      explores the genetic stability of host factors indispensable for influenza virus
      replication would thus be desirable. Here, we characterized the rRNA processing 1
      homolog B (RRP1B) protein as an important cellular factor for influenza A virus
      transcription. We showed that silencing RRP1B hampered viral RNA-dependent RNA
      polymerase (RdRp) activity, which is responsible for virus transcription and
      replication. Furthermore, we reported that RRP1B is crucial for RdRp binding to
      cellular capped mRNA, which is a critical step of virus transcription. Our study
      not only provides a deeper understanding of influenza virus-host interplay, but
      also suggests a potential target for antiviral drug development.

PMID- 26311877
TI  - Remote Activation of Host Cell DNA Synthesis in Uninfected Cells Signaled by
      Infected Cells in Advance of Virus Transmission.
AB  - Viruses modulate cellular processes and metabolism in diverse ways, but these are
      almost universally studied in the infected cell itself. Here, we study spatial
      organization of DNA synthesis during multiround transmission of herpes simplex
      virus (HSV) using pulse-labeling with ethynyl nucleotides and cycloaddition of
      azide fluorophores. We report a hitherto unknown and unexpected outcome of virus
      host interaction. Consistent with the current understanding of the single-step
      growth cycle, HSV suppresses host DNA synthesis and promotes viral DNA synthesis
      in spatially segregated compartments within the cell. In striking contrast,
      during progressive rounds of infection initiated at a single cell, we observe
      that infection induces a clear and pronounced stimulation of cellular DNA
      replication in remote uninfected cells. This induced DNA synthesis was observed
      in hundreds of uninfected cells at the extended border, outside the perimeter of
      the progressing infection. Moreover, using pulse-chase analysis, we show that
      this activation is maintained, resulting in a propagating wave of host DNA
      synthesis continually in advance of infection. As the virus reaches and infects
      these activated cells, host DNA synthesis is then shut off and replaced with
      virus DNA synthesis. Using nonpropagating viruses or conditioned medium, we
      demonstrate a paracrine effector of uninfected cell DNA synthesis in remote cells
      continually in advance of infection. These findings have significant
      implications, likely with broad applicability, for our understanding of the ways
      in which virus infection manipulates cell processes not only in the infected cell
      itself but also now in remote uninfected cells, as well as of mechanisms
      governing host DNA synthesis. IMPORTANCE: We show that during infection initiated
      by a single particle with progressive cell-cell virus transmission (i.e., the
      normal situation), HSV induces host DNA synthesis in uninfected cells, mediated
      by a virus-induced paracrine effector. The field has had no conception that this
      process occurs, and the work changes our interpretation of virus-host interaction
      during advancing infection and has implications for understanding controls of
      host DNA synthesis. Our findings demonstrate the utility of chemical biology
      techniques in analysis of infection processes, reveal distinct processes when
      infection is examined in multiround transmission versus single-step growth
      curves, and reveal a hitherto-unknown process in virus infection, likely relevant
      for other viruses (and other infectious agents) and for remote signaling of other
      processes, including transcription and protein synthesis.

PMID- 26311878
TI  - The Combination of the R263K and T66I Resistance Substitutions in HIV-1 Integrase
      Is Incompatible with High-Level Viral Replication and the Development of High
      Level Drug Resistance.
AB  - The R263K substitution in integrase has been selected in tissue culture with
      dolutegravir (DTG) and has been reported for several treatment-experienced
      individuals receiving DTG as part of salvage therapy. The R263K substitution
      seems to be incompatible with the presence of common resistance mutations
      associated with raltegravir (RAL), a different integrase strand transfer
      inhibitor (INSTI). T66I is a substitution that is common in individuals who have
      developed resistance against a different INSTI termed elvitegravir (EVG), but it
      is not known whether these two mutations might be compatible in the context of
      resistance against DTG or what impact the combination of these substitutions
      might have on resistance against INSTIs. E138K is a common secondary substitution
      observed with various primary resistance substitutions in RAL- and EVG-treated
      individuals. Viral infectivity, replicative capacity, and resistance against
      INSTIs were measured in cell-based assays. Strand transfer and 3' processing
      activities were measured biochemically. The combination of the R263K and T66I
      substitutions decreased HIV-1 infectivity, replicative capacity, and strand
      transfer activity. The addition of the E138K substitution partially compensated
      for these deficits and resulted in high levels of resistance against EVG but not
      against DTG or RAL. These findings suggest that the presence of the T66I
      substitution will not compromise the activity of DTG and may also help to prevent
      the additional generation of the R263K mutation. Our observations support the use
      of DTG in second-line therapy for individuals who experience treatment failure
      with EVG due to the T66I substitution. IMPORTANCE: The integrase strand transfer
      inhibitors (INSTIs) elvitegravir and dolutegravir are newly developed inhibitors
      against human immunodeficiency virus type 1 (HIV-1). HIV drug-resistant mutations
      in integrase that can arise in individuals treated with elvitegravir commonly
      include the T66I substitution, whereas R263K is a signature resistance
      substitution against dolutegravir. In order to determine how different
      combinations of integrase resistance mutations can influence the outcome of
      therapy, we report here the effects of the T66I, E138K, and R263K substitutions,
      alone and in combination, on viral replicative capacity and resistance to
      integrase inhibitors. Our results show that the addition of R263K to the T66I
      substitution diminishes viral replicative capacity and strand transfer activity
      while not compromising susceptibility to dolutegravir. This supports the use of
      dolutegravir in second-line therapy for patients failing elvitegravir therapy who
      harbor the T66I resistance substitution.

PMID- 26311879
TI  - Role of the DNA Sensor STING in Protection from Lethal Infection following
      Corneal and Intracerebral Challenge with Herpes Simplex Virus 1.
AB  - STING is a protein in the cytosolic DNA and cyclic dinucleotide sensor pathway
      that is critical for the initiation of innate responses to infection by various
      pathogens. Consistent with this, herpes simplex virus 1 (HSV-1) causes invariable
      and rapid lethality in STING-deficient (STING(-/-)) mice following intravenous
      (i.v.) infection. In this study, using real-time bioluminescence imaging and
      virological assays, as expected, we demonstrated that STING(-/-) mice support
      greater replication and spread in ocular tissues and the nervous system. In
      contrast, they did not succumb to challenge via the corneal route even with high
      titers of a virus that was routinely lethal to STING(-/-) mice by the i.v. route.
      Corneally infected STING(-/-) mice also showed increased periocular disease and
      increased corneal and trigeminal ganglia titers, although there was no difference
      in brain titers. They also showed elevated expression of tumor necrosis factor
      alpha (TNF-alpha) and CXCL9 relative to control mice but surprisingly modest
      changes in type I interferon expression. Finally, we also showed that HSV strains
      lacking the ability to counter autophagy and the PKR-driven antiviral state had
      near-wild-type virulence following intracerebral infection of STING(-/-) mice.
      Together, these data show that while STING is an important component of host
      resistance to HSV in the cornea, its previously shown immutable role in mediating
      host survival by the i.v. route was not recapitulated following a mucosal
      infection route. Furthermore, our data are consistent with the idea that HSV
      counters STING-mediated induction of the antiviral state and autophagy response,
      both of which are critical factors for survival following direct infection of the
      nervous system. IMPORTANCE: HSV infections represent an incurable source of
      morbidity and mortality in humans and are especially severe in neonatal and
      immunocompromised populations. A key step in the development of an immune
      response is the recognition of microbial components within infected cells. The
      host protein STING is important in this regard for the recognition of HSV DNA and
      the subsequent triggering of innate responses. STING was previously shown to be
      essential for protection against lethal challenge from intravenous HSV-1
      infection. In this study, we show that the requirement for STING depends on the
      infection route. In addition, STING is important for appropriate regulation of
      the inflammatory response in the cornea, and our data are consistent with the
      idea that HSV modulates STING activity through inhibition of autophagy. Our
      results elucidate the importance of STING in host protection from HSV-1 and
      demonstrate the redundancy of host protective mechanisms, especially following
      mucosal infection.

PMID- 26311880
TI  - Positive Selection in CD8+ T-Cell Epitopes of Influenza Virus Nucleoprotein
      Revealed by a Comparative Analysis of Human and Swine Viral Lineages.
AB  - Numerous experimental studies have demonstrated that CD8(+) T cells contribute to
      immunity against influenza by limiting viral replication. It is therefore
      surprising that rigorous statistical tests have failed to find evidence of
      positive selection in the epitopes targeted by CD8(+) T cells. Here we use a
      novel computational approach to test for selection in CD8(+) T-cell epitopes. We
      define all epitopes in the nucleoprotein (NP) and matrix protein (M1) with
      experimentally identified human CD8(+) T-cell responses and then compare the
      evolution of these epitopes in parallel lineages of human and swine influenza
      viruses that have been diverging since roughly 1918. We find a significant
      enrichment of substitutions that alter human CD8(+) T-cell epitopes in NP of
      human versus swine influenza virus, consistent with the idea that these epitopes
      are under positive selection. Furthermore, we show that epitope-altering
      substitutions in human influenza virus NP are enriched on the trunk versus the
      branches of the phylogenetic tree, indicating that viruses that acquire these
      mutations have a selective advantage. However, even in human influenza virus NP,
      sites in T-cell epitopes evolve more slowly than do nonepitope sites, presumably
      because these epitopes are under stronger inherent functional constraint.
      Overall, our work demonstrates that there is clear selection from CD8(+) T cells
      in human influenza virus NP and illustrates how comparative analyses of viral
      lineages from different hosts can identify positive selection that is otherwise
      obscured by strong functional constraint. IMPORTANCE: There is a strong interest
      in correlates of anti-influenza immunity that are protective against diverse
      virus strains. CD8(+) T cells provide such broad immunity, since they target
      conserved viral proteins. An important question is whether T-cell immunity is
      sufficiently strong to drive influenza virus evolution. Although many studies
      have shown that T cells limit viral replication in animal models and are
      associated with decreased symptoms in humans, no studies have proven with
      statistical significance that influenza virus evolves under positive selection to
      escape T cells. Here we use comparisons of human and swine influenza viruses to
      rigorously demonstrate that human influenza virus evolves under pressure to fix
      mutations in the nucleoprotein that promote escape from T cells. We further show
      that viruses with these mutations have a selective advantage since they are
      preferentially located on the "trunk" of the phylogenetic tree. Overall, our
      results show that CD8(+) T cells targeting nucleoprotein play an important role
      in shaping influenza virus evolution.

PMID- 26311881
TI  - Reorganization of Nuclear Pore Complexes and the Lamina in Late-Stage Parvovirus
      Infection.
AB  - Canine parvovirus (CPV) infection induces reorganization of nuclear structures.
      Our studies indicated that late-stage infection induces accumulation of nuclear
      pore complexes (NPCs) and lamin B1 concomitantly with a decrease of lamin A/C
      levels on the apical side of the nucleus. Newly formed CPV capsids are located in
      close proximity to NPCs on the apical side. These results suggest that
      parvoviruses cause apical enrichment of NPCs and reorganization of nuclear
      lamina, presumably to facilitate the late-stage infection. 

PMID- 26311882
TI  - Host Gene Expression Is Regulated by Two Types of Noncoding RNAs Transcribed from
      the Epstein-Barr Virus BamHI A Rightward Transcript Region.
AB  - In Epstein-Barr virus-infected epithelial cancers, the alternatively spliced
      BamHI A rightward transcripts (BARTs) are the most abundant viral polyadenylated
      RNA. The BART introns form the template for the production of 44 microRNAs
      (miRNAs), and the spliced and polyadenylated exons form nuclear non-protein
      coding RNAs. Analysis of host cell transcription by RNA-seq during latency in AGS
      cells identified a large number of reproducibly changed genes. Genes that were
      downregulated were enriched for BART miRNA targets. Bioinformatics analysis
      predicted activation of the myc pathway and downregulation of XBP1 as likely
      mediators of the host transcriptional changes. Effects on XBP1 activity were not
      detected in these cells; however, myc activation was confirmed through use of a
      myc-responsive luciferase reporter. To identify potential regulatory properties
      of the spliced, polyadenylated BART RNAs, a full-length cDNA clone of one of the
      BART isoforms was obtained and expressed in the Epstein-Barr virus (EBV)-negative
      AGS cells. The BART cDNA transcript remained primarily nuclear yet induced
      considerable and consistent changes in cellular transcription, as profiled by RNA
      seq. These transcriptional changes significantly overlapped the transcriptional
      changes induced during latent EBV infection of these same cells, where the BARTs
      are exclusively nuclear and do not encode proteins. These data suggest that the
      nuclear BART RNAs are functional long noncoding RNAs (lncRNAs). The abundant
      expression of multiple forms of noncoding RNAs that contribute to growth
      regulation without expression of immunogenic proteins would be an important
      mechanism for viral oncogenesis in the presence of a functional immune system.
      IMPORTANCE: Infection with Epstein-Barr virus (EBV) is nearly ubiquitous in the
      human population; however, it does contribute to the formation of multiple types
      of cancer. In immunocompromised patients, EBV causes multiple types of lymphomas
      by expressing viral oncogenes that promote growth and survival of infected B
      lymphocytes. EBV-positive gastric carcinoma does not require immune suppression,
      and the viral oncoproteins that are frequent targets for an immunological
      response are not expressed. This study demonstrates using transcriptional
      analysis that the expression of various classes of viral non-protein-coding RNAs
      likely contribute to the considerable changes in the host transcriptional profile
      in the AGS gastric cancer cell line. This is the first report to show that the
      highly expressed polyadenylated BamHI A rightward transcripts (BART) viral
      transcript in gastric carcinoma is in fact a functional viral long noncoding RNA.
      These studies provide new insight into how EBV can promote transformation in the
      absence of viral protein expression.

PMID- 26311883
TI  - Viral Polymerase-Helicase Complexes Regulate Replication Fidelity To Overcome
      Intracellular Nucleotide Depletion.
AB  - To date, the majority of work on RNA virus replication fidelity has focused on
      the viral RNA polymerase, while the potential role of other viral replicase
      proteins in this process is poorly understood. Previous studies used resistance
      to broad-spectrum RNA mutagens, such as ribavirin, to identify polymerases with
      increased fidelity that avoid misincorporation of such base analogues. We
      identified a novel variant in the alphavirus viral helicase/protease,
      nonstructural protein 2 (nsP2) that operates in concert with the viral polymerase
      nsP4 to further alter replication complex fidelity, a functional linkage that was
      conserved among the alphavirus genus. Purified chikungunya virus nsP2 presented
      delayed helicase activity of the high-fidelity enzyme, and yet purified
      replication complexes manifested stronger RNA polymerization kinetics. Because
      mutagenic nucleoside analogs such as ribavirin also affect intracellular
      nucleotide pools, we addressed the link between nucleotide depletion and
      replication fidelity by using purine and pyrimidine biosynthesis inhibitors. High
      fidelity viruses were more resistant to these conditions, and viral growth could
      be rescued by the addition of exogenous nucleosides, suggesting that mutagenesis
      by base analogues requires nucleotide pool depletion. This study describes a
      novel function for nsP2, highlighting the role of other components of the
      replication complex in regulating viral replication fidelity, and suggests that
      viruses can alter their replication complex fidelity to overcome intracellular
      nucleotide-depleting conditions. IMPORTANCE: Previous studies using the RNA
      mutagen ribavirin to select for drug-resistant variants have highlighted the
      essential role of the viral RNA-dependent RNA polymerase in regulating
      replication fidelity. However, the role of other viral replicase components in
      replication fidelity has not been studied in detail. We identified here an RNA
      mutagen-resistant variant of the nsP2 helicase/protease that conferred increased
      fidelity and yet could not operate in the same manner as high-fidelity
      polymerases. We show that the alphavirus helicase is a key component of the
      fidelity-regulating machinery. Our data show that the RNA mutagenic activity of
      compounds such as ribavirin is coupled to and potentiated by nucleotide depletion
      and that RNA viruses can fine-tune their replication fidelity when faced with an
      intracellular environment depleted of nucleotides.

PMID- 26311884
TI  - Genome-Wide Screen Reveals Valosin-Containing Protein Requirement for Coronavirus
      Exit from Endosomes.
AB  - Coronaviruses are RNA viruses with a large zoonotic reservoir and propensity for
      host switching, representing a real threat for public health, as evidenced by
      severe acute respiratory syndrome (SARS) and the emerging Middle East respiratory
      syndrome (MERS). Cellular factors required for their replication are poorly
      understood. Using genome-wide small interfering RNA (siRNA) screening, we
      identified 83 novel genes supporting infectious bronchitis virus (IBV)
      replication in human cells. Thirty of these hits can be placed in a network of
      interactions with viral proteins and are involved in RNA splicing, membrane
      trafficking, and ubiquitin conjugation. In addition, our screen reveals an
      unexpected role for valosin-containing protein (VCP/p97) in early steps of
      infection. Loss of VCP inhibits a previously uncharacterized degradation of the
      nucleocapsid N protein. This inhibition derives from virus accumulation in early
      endosomes, suggesting a role for VCP in the maturation of virus-loaded endosomes.
      The several host factors identified in this study may provide avenues for
      targeted therapeutics. IMPORTANCE: Coronaviruses are RNA viruses representing a
      real threat for public health, as evidenced by SARS and the emerging MERS.
      However, cellular factors required for their replication are poorly understood.
      Using genome-wide siRNA screening, we identified novel genes supporting
      infectious bronchitis virus (IBV) replication in human cells. The several host
      factors identified in this study may provide directions for future research on
      targeted therapeutics.

PMID- 26311885
TI  - Middle East Respiratory Syndrome Coronavirus nsp1 Inhibits Host Gene Expression
      by Selectively Targeting mRNAs Transcribed in the Nucleus while Sparing mRNAs of
      Cytoplasmic Origin.
AB  - The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) and
      severe acute respiratory syndrome CoV (SARS-CoV) represent highly pathogenic
      human CoVs that share a property to inhibit host gene expression at the
      posttranscriptional level. Similar to the nonstructural protein 1 (nsp1) of SARS
      CoV that inhibits host gene expression at the translational level, we report that
      MERS-CoV nsp1 also exhibits a conserved function to negatively regulate host gene
      expression by inhibiting host mRNA translation and inducing the degradation of
      host mRNAs. Furthermore, like SARS-CoV nsp1, the mRNA degradation activity of
      MERS-CoV nsp1, most probably triggered by its ability to induce an
      endonucleolytic RNA cleavage, was separable from its translation inhibitory
      function. Despite these functional similarities, MERS-CoV nsp1 used a strikingly
      different strategy that selectively targeted translationally competent host mRNAs
      for inhibition. While SARS-CoV nsp1 is localized exclusively in the cytoplasm and
      binds to the 40S ribosomal subunit to gain access to translating mRNAs, MERS-CoV
      nsp1 was distributed in both the nucleus and the cytoplasm and did not bind
      stably to the 40S subunit, suggesting a distinctly different mode of targeting
      translating mRNAs. Interestingly, consistent with this notion, MERS-CoV nsp1
      selectively targeted mRNAs, which are transcribed in the nucleus and transported
      to the cytoplasm, for translation inhibition and mRNA degradation but spared
      exogenous mRNAs introduced directly into the cytoplasm or virus-like mRNAs that
      originate in the cytoplasm. Collectively, these data point toward a novel viral
      strategy wherein the cytoplasmic origin of MERS-CoV mRNAs facilitates their
      escape from the inhibitory effects of MERS-CoV nsp1. IMPORTANCE: Middle East
      respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic human CoV that
      emerged in Saudi Arabia in 2012. MERS-CoV has a zoonotic origin and poses a major
      threat to public health. However, little is known about the viral factors
      contributing to the high virulence of MERS-CoV. Many animal viruses, including
      CoVs, encode proteins that interfere with host gene expression, including those
      involved in antiviral immune responses, and these viral proteins are often major
      virulence factors. The nonstructural protein 1 (nsp1) of CoVs is one such protein
      that inhibits host gene expression and is a major virulence factor. This study
      presents evidence for a strategy used by MERS-CoV nsp1 to inhibit host gene
      expression that has not been described previously for any viral protein. The
      present study represents a meaningful step toward a better understanding of the
      factors and molecular mechanisms governing the virulence and pathogenesis of MERS
      CoV.

PMID- 26311886
TI  - Bst2/Tetherin Is Induced in Neurons by Type I Interferon and Viral Infection but
      Is Dispensable for Protection against Neurotropic Viral Challenge.
AB  - In permissive mouse central nervous system (CNS) neurons, measles virus (MV)
      spreads in the absence of hallmark viral budding or neuronal death, with
      transmission occurring efficiently and exclusively via the synapse. MV infection
      also initiates a robust type I interferon (IFN) response, resulting in the
      synthesis of a large number of genes, including bone marrow stromal antigen 2
      (Bst2)/tetherin/CD317. Bst2 restricts the release of some enveloped viruses, but
      to date, its role in viral infection of neurons has not been assessed.
      Consequently, we investigated how Bst2 was induced and what role it played in MV
      neuronal infection. The magnitude of induction of neuronal Bst2 RNA and protein
      following IFN exposure and viral infection was notably higher than in similarly
      treated mouse embryo fibroblasts (MEFs). Bst2 synthesis was both IFN and Stat1
      dependent. Although Bst2 prevented MV release from nonneuronal cells, its
      deletion had no effect on viral pathogenesis in MV-challenged mice. Our findings
      underscore how cell-type-specific differences impact viral infection and
      pathogenesis. IMPORTANCE: Viral infections of the central nervous system can lead
      to debilitating disease and death. Moreover, it is becoming increasingly clear
      that nonrenewable cells, including most central nervous system neurons, combat
      neurotropic viral infections in fundamentally different ways than other rapidly
      dividing and renewable cell populations. Here we identify type I interferon
      signaling as a key inducer of a known antiviral protein (Bst2) in neurons.
      Unexpectedly, the gene is dispensable for clearance of neurotropic viral
      infection despite its well-defined contribution to limiting the spread of
      enveloped viruses in proliferating cells. A deeper appreciation of the importance
      of cell type heterogeneity in antiviral immunity will aid in the identification
      of unique therapeutic targets for life-threatening viral infections.

PMID- 26311887
TI  - Oligomerization of Mumps Virus Phosphoprotein.
AB  - The mumps virus (MuV) genome encodes a phosphoprotein (P) that is important for
      viral RNA synthesis. P forms the viral RNA-dependent RNA polymerase with the
      large protein (L). P also interacts with the viral nucleoprotein (NP) and self
      associates to form a homotetramer. The P protein consists of three domains, the N
      terminal domain (P(N)), the oligomerization domain (P(O)), and the C-terminal
      domain (P(C)). While P(N) is known to relax the NP-bound RNA genome, the roles of
      P(O) and P(C) are not clear. In this study, we investigated the roles of P(O) and
      P(C) in viral RNA synthesis using mutational analysis and a minigenome system. We
      found that P(N) and P(C) functions can be trans-complemented. However, this
      complementation requires P(O), indicating that P(O) is essential for P function.
      Using this trans-complementation system, we found that P forms parallel dimers
      (P(N) to P(N) and P(C) to P(C)). Furthermore, we found that residues R231, K238,
      K253, and K260 in P(O) are critical for P's functions. We identified P(C) to be
      the domain that interacts with L. These results provide structure-function
      insights into the role of MuV P. IMPORTANCE: MuV, a paramyxovirus, is an
      important human pathogen. The P protein of MuV is critical for viral RNA
      synthesis. In this work, we established a novel minigenome system that allows the
      domains of P to be complemented in trans. Using this system, we confirmed that
      MuV P forms parallel dimers. An understanding of viral RNA synthesis will allow
      the design of better vaccines and the development of antivirals.

PMID- 26311888
TI  - Characterization of the Interaction between the Matrix Protein of Vesicular
      Stomatitis Virus and the Immunoproteasome Subunit LMP2.
AB  - The matrix protein (M) of vesicular stomatitis virus (VSV) is involved in virus
      assembly, budding, gene regulation, and cellular pathogenesis. Using a yeast two
      hybrid system, the M globular domain was shown to interact with LMP2, a catalytic
      subunit of the immunoproteasome (which replaces the standard proteasome catalytic
      subunit PSMB6). The interaction was validated by coimmunoprecipitation of M and
      LMP2 in VSV-infected cells. The sites of interaction were characterized. A single
      mutation of M (I96A) which significantly impairs the interaction between M and
      LMP2 was identified. We also show that M preferentially binds to the inactive
      precursor of LMP2 (bearing an N-terminal propeptide which is cleaved upon LMP2
      maturation). Furthermore, taking advantage of a sequence alignment between LMP2
      and its proteasome homolog, PSMB6 (which does not bind to M), we identified a
      mutation (L45R) in the S1 pocket where the protein substrate binds prior to
      cleavage and a second one (D17A) of a conserved residue essential for the
      catalytic activity, resulting in a reduction of the level of binding to M. The
      combination of both mutations abolishes the interaction. Taken together, our data
      indicate that M binds to LMP2 before its incorporation into the immunoproteasome.
      As the immunoproteasome promotes the generation of major histocompatibility
      complex (MHC) class I-compatible peptides, a feature which favors the recognition
      and the elimination of infected cells by CD8 T cells, we suggest that M, by
      interfering with the immunoproteasome assembly, has evolved a mechanism that
      allows infected cells to escape detection and elimination by the immune system.
      IMPORTANCE: The immunoproteasome promotes the generation of MHC class I
      compatible peptides, a feature which favors the recognition and the elimination
      of infected cells by CD8 T cells. Here, we report on the association of vesicular
      stomatitis virus (VSV) matrix protein (M) with LMP2, one of the immunoproteasome
      specific catalytic subunits. M preferentially binds to the LMP2 inactive
      precursor. The M-binding site on LMP2 is facing inwards in the immunoproteasome
      and is therefore not accessible to M after its assembly. Hence, M binds to LMP2
      before its incorporation into the immunoproteasome. We suggest that VSV M, by
      interfering with the immunoproteasome assembly, has evolved a mechanism that
      allows infected cells to escape detection and elimination by the immune system.
      Modulating this M-induced immunoproteasome impairment might be relevant in order
      to optimize VSV for oncolytic virotherapy.

PMID- 26311889
TI  - Infectious Bursal Disease Virus VP3 Upregulates VP1-Mediated RNA-Dependent RNA
      Replication.
AB  - Genome replication is a critical step in virus life cycles. Here, we analyzed the
      role of the infectious bursal disease virus (IBDV) VP3, a major component of IBDV
      ribonucleoprotein complexes, on the regulation of VP1, the virus-encoded RNA
      dependent RNA polymerase (RdRp). Data show that VP3, as well as a peptide
      mimicking its C-terminal domain, efficiently stimulates the ability of VP1 to
      replicate synthetic single-stranded RNA templates containing the 3' untranslated
      regions (UTRs) from the IBDV genome segments. 

PMID- 26311890
TI  - Evolutionary Dynamics and Global Diversity of Influenza A Virus.
AB  - The increasing number of zoonotic infections caused by influenza A virus (IAV)
      subtypes of avian origin (e.g., H5N1 and H7N9) in recent years underscores the
      need to better understand the factors driving IAV evolution and diversity. To
      evaluate the current feasibility of global analyses to contribute to this aim, we
      evaluated information in the public domain to explore IAV evolutionary dynamics,
      including nucleotide substitution rates and selection pressures, using 14 IAV
      subtypes in 32 different countries over a 12-year period (2000 to 2011). Using
      geospatial information from 39,785 IAV strains, we examined associations between
      subtype diversity and socioeconomic, biodiversity, and agricultural indices. Our
      analyses showed that nucleotide substitution rates for 11 of the 14 evaluated
      subtypes tended to be higher in Asian countries, particularly in East Asia, than
      in Canada and the United States. Similarly, at a regional level, subtypes H5N1,
      H5N2, and H6N2 exhibited significantly higher substitution rates in East Asia
      than in North America. In contrast, the selection pressures (measured as ratios
      of nonsynonymous to synonymous evolutionary changes [dN/dS ratios]) acting on
      individual subtypes showed little geographic variation. We found that the
      strongest predictors for the detected subtype diversity at the country level were
      reporting effort (i.e., total number of strains reported) and health care
      spending (an indicator of economic development). Our analyses also identified
      major global gaps in IAV reporting (including a lack of sequences submitted from
      large portions of Africa and South America and a lack of geolocation information)
      and in broad subtype testing which, until addressed, will continue to hinder
      efforts to track the evolution and diversity of IAV around the world. IMPORTANCE:
      In recent years, an increasing number of influenza A virus (IAV) subtypes,
      including H5N1, H7N9, and H10N8, have been detected in humans. High fatality
      rates have led to an increased urgency to better understand where and how novel
      pathogenic influenza virus strains emerge. Our findings showed that mutational
      rates of 11 commonly encountered subtypes were higher in East Asian countries
      than in North America, suggesting that there may be a greater risk for the
      emergence of novel pathogenic strains in East Asia. In assessing the potential
      drivers of IAV subtype diversity, our analyses confirmed that reporting effort
      and health care spending were the best predictors of the observed subtype
      diversity at the country level. These findings underscore the need to increase
      sampling and reporting efforts for all subtypes in many undersampled countries
      throughout the world.

PMID- 26311891
TI  - Out of the Reservoir: Phenotypic and Genotypic Characterization of a Novel Cowpox
      Virus Isolated from a Common Vole.
AB  - The incidence of human cowpox virus (CPXV) infections has increased significantly
      in recent years. Serological surveys have suggested wild rodents as the main CPXV
      reservoir. We characterized a CPXV isolated during a large-scale screening from a
      feral common vole. A comparison of the full-length DNA sequence of this CPXV
      strain with a highly virulent pet rat CPXV isolate showed a sequence identity of
      96%, including a large additional open reading frame (ORF) of about 6,000
      nucleotides which is absent in the reference CPXV strain Brighton Red. Electron
      microscopy analysis demonstrated that the vole isolate, in contrast to the rat
      strain, forms A-type inclusion (ATI) bodies with incorporated virions, consistent
      with the presence of complete ati and p4c genes. Experimental infections showed
      that the vole CPXV strain caused only mild clinical symptoms in its natural host,
      while all rats developed severe respiratory symptoms followed by a systemic rash.
      In contrast, common voles infected with a high dose of the rat CPXV showed severe
      signs of respiratory disease but no skin lesions, whereas infection with a low
      dose led to virus excretion with only mild clinical signs. We concluded that the
      common vole is susceptible to infection with different CPXV strains. The spectrum
      ranges from well-adapted viruses causing limited clinical symptoms to highly
      virulent strains causing severe respiratory symptoms. In addition, the low
      pathogenicity of the vole isolate in its eponymous host suggests a role of common
      voles as a major CPXV reservoir, and future research will focus on the
      correlation between viral genotype and phenotype/pathotype in accidental and
      reservoir species. IMPORTANCE: We report on the first detection and isolation of
      CPXV from a putative reservoir host, which enables comparative analyses to
      understand the infection cycle of these zoonotic orthopox viruses and the
      relevant genes involved. In vitro studies, including whole-genome sequencing as
      well as in vivo experiments using the Wistar rat model and the vole reservoir
      host allowed us to establish links between genomic sequences and the in vivo
      properties (virulence) of the novel vole isolate in comparison to those of a
      recent zoonotic CPXV isolated from pet rats in 2009. Furthermore, the role of
      genes present only in a reservoir isolate can now be further analyzed. These
      studies therefore allow unique insights and conclusions about the role of the
      rodent reservoir in CPXV epidemiology and transmission and about the zoonotic
      threat that these viruses represent.

PMID- 26311892
TI  - Spatiotemporal Reconstruction of the Introduction of Hepatitis C Virus into
      Scotland and Its Subsequent Regional Transmission.
AB  - A more comprehensive understanding of hepatitis C virus (HCV) transmission
      dynamics could facilitate public health initiatives to reduce the prevalence of
      HCV in people who inject drugs. We aimed to determine how HCV sequences entered
      and spread throughout Scotland and to identify transmission hot spots. A Scottish
      data set with embedded demographic data was created by sequencing the NS5B of 125
      genotype 1a (Gt1a) samples and 166 Gt3a samples and analyzed alongside sequences
      from public databases. Applying Bayesian inference methods, we reconstructed the
      global origin and local spatiotemporal dissemination of HCV in Scotland. Scottish
      sequences mainly formed discrete clusters interspersed between sequences from the
      rest of the world; the most recent common ancestors of these clusters dated to
      1942 to 1952 (Gt1a) and 1926 to 1942 (Gt3a), coincident with global
      diversification and distribution. Extant Scottish sequences originated in
      Edinburgh (Gt1a) and Glasgow (Gt3a) in the 1970s, but both genotypes spread from
      Glasgow to other regions. The dominant Gt1a strain differed between Edinburgh
      (cluster 2 [C2]), Glasgow (C3), and Aberdeen (C4), whereas significant Gt3a
      strain specificity occurred only in Aberdeen. Specific clusters initially formed
      separate transmission zones in Glasgow that subsequently overlapped, occasioning
      city-wide cocirculation. Transmission hot spots were detected with 45% of samples
      from patients residing in just 9 of Glasgow's 57 postcode districts. HCV was
      introduced into Scotland in the 1940s, concomitant with its worldwide dispersal
      likely arising from global-scale historical events. Cluster-specific transmission
      hubs were identified in Glasgow, the key Scottish city implicated in HCV
      dissemination. This fine-scale spatiotemporal reconstruction improves
      understanding of HCV transmission dynamics in Scotland. IMPORTANCE: HCV is a
      major health burden and the leading cause of hepatocellular carcinoma. Public
      health needle exchange and "treatment as prevention" strategies targeting HCV are
      designed to reduce prevalence of the virus in people who inject drugs (PWID),
      potentially mitigating the future burden of HCV-associated liver disease.
      Understanding HCV transmission dynamics could increase the effectiveness of such
      public health initiatives by identifying and targeting regions playing a central
      role in virus dispersal. In this study, we examined HCV transmission in Scotland
      by analyzing the genetic relatedness of strains from PWID alongside data
      inferring the year individuals became infected and residential information at a
      geographically finer-scale resolution than in previous studies. Clusters of
      Scotland-specific strains were identified with regional specificity, and mapping
      the spread of HCV allowed the identification of key areas central to HCV
      transmission in Scotland. This research provides a basis for identifying HCV
      transmission hot spots.

PMID- 26311894
TI  - Cross-Species Infectivity of H3N8 Influenza Virus in an Experimental Infection in
      Swine.
AB  - Avian influenza A viruses have gained increasing attention due to their ability
      to cross the species barrier and cause severe disease in humans and other mammal
      species as pigs. H3 and particularly H3N8 viruses, are highly adaptive since they
      are found in multiple avian and mammal hosts. H3N8 viruses have not been isolated
      yet from humans; however, a recent report showed that equine influenza A viruses
      (IAVs) can be isolated from pigs, although an established infection has not been
      observed thus far in this host. To gain insight into the possibility of H3N8
      avian IAVs to cross the species barrier into pigs, in vitro experiments and an
      experimental infection in pigs with four H3N8 viruses from different origins
      (equine, canine, avian, and seal) were performed. As a positive control, an H3N2
      swine influenza virus A was used. Although equine and canine viruses hardly
      replicated in the respiratory systems of pigs, avian and seal viruses replicated
      substantially and caused detectable lesions in inoculated pigs without previous
      adaptation. Interestingly, antibodies against hemagglutinin could not be detected
      after infection by hemagglutination inhibition (HAI) test with avian and seal
      viruses. This phenomenon was observed not only in pigs but also in mice immunized
      with the same virus strains. Our data indicated that H3N8 IAVs from wild aquatic
      birds have the potential to cross the species barrier and establish successful
      infections in pigs that might spread unnoticed using the HAI test as diagnostic
      tool. IMPORTANCE: Although natural infection of humans with an avian H3N8
      influenza A virus has not yet been reported, this influenza A virus subtype has
      already crossed the species barrier. Therefore, we have examined the potential of
      H3N8 from canine, equine, avian, and seal origin to productively infect pigs. Our
      results demonstrated that avian and seal viruses replicated substantially and
      caused detectable lesions in inoculated pigs without previous adaptation.
      Surprisingly, we could not detect specific antibodies against hemagglutinin in
      any H3N8-infected pigs. Therefore, special attention should be focused toward
      viruses of the H3N8 subtype since they could behave as stealth viruses in pigs.

PMID- 26311893
TI  - Influences on the Design and Purification of Soluble, Recombinant Native-Like HIV
      1 Envelope Glycoprotein Trimers.
AB  - We have investigated factors that influence the production of native-like
      soluble, recombinant trimers based on the env genes of two isolates of human
      immunodeficiency virus type 1 (HIV-1), specifically 92UG037.8 (clade A) and
      CZA97.012 (clade C). When the recombinant trimers based on the env genes of
      isolates 92UG037.8 and CZA97.012 were made according to the SOSIP.664 design and
      purified by affinity chromatography using broadly neutralizing antibodies (bNAbs)
      against quaternary epitopes (PGT145 and PGT151, respectively), the resulting
      trimers are highly stable and they are fully native-like when visualized by
      negative-stain electron microscopy. They also have a native-like (i.e., abundant)
      oligomannose glycan composition and display multiple bNAb epitopes while
      occluding those for nonneutralizing antibodies. In contrast, uncleaved, histidine
      tagged Foldon (Fd) domain-containing gp140 proteins (gp140UNC-Fd-His), based on
      the same env genes, very rarely form native-like trimers, a finding that is
      consistent with their antigenic and biophysical properties and glycan
      composition. The addition of a 20-residue flexible linker (FL20) between the
      gp120 and gp41 ectodomain (gp41ECTO) subunits to make the uncleaved 92UG037.8
      gp140-FL20 construct is not sufficient to create a native-like trimer, but a
      small percentage of native-like trimers were produced when an I559P substitution
      in gp41ECTO was also present. The further addition of a disulfide bond (SOS) to
      link the gp120 and gp41 subunits in the uncleaved gp140-FL20-SOSIP protein
      increases native-like trimer formation to ~20 to 30%. Analysis of the disulfide
      bond content shows that misfolded gp120 subunits are abundant in uncleaved
      CZA97.012 gp140UNC-Fd-His proteins but very rare in native-like trimer
      populations. The design and stabilization method and the purification strategy
      are, therefore, all important influences on the quality of trimeric Env proteins
      and hence their suitability as vaccine components. IMPORTANCE: Soluble,
      recombinant multimeric proteins based on the HIV-1 env gene are current candidate
      immunogens for vaccine trials in humans. These proteins are generally designed to
      mimic the native trimeric envelope glycoprotein (Env) that is the target of virus
      neutralizing antibodies on the surfaces of virions. The underlying hypothesis is
      that an Env-mimetic protein may be able to induce antibodies that can neutralize
      the virus broadly and potently enough for a vaccine to be protective. Multiple
      different designs for Env-mimetic trimers have been put forth. Here, we used the
      CZA97.012 and 92UG037.8 env genes to compare some of these designs and determine
      which ones best mimic virus-associated Env trimers. We conclude that the most
      widely used versions of CZA97.012 and 92UG037.8 oligomeric Env proteins do not
      resemble the trimeric Env glycoprotein on HIV-1 viruses, which has implications
      for the design and interpretation of ongoing or proposed clinical trials of these
      proteins.

PMID- 26311896
TI  - First-borns have greater BMI and are more likely to be overweight or obese: a
      study of sibling pairs among 26,812 Swedish women.
AB  - BACKGROUND: A number of large studies have shown phenotypic differences between
      first-borns and later-borns among adult men. In this study, we aimed to assess
      whether birth order was associated with height and BMI in a large cohort of
      Swedish women. METHODS: Information was obtained from antenatal clinic records
      from the Swedish National Birth Register over 20 years (1991-2009). Maternal
      anthropometric data early in pregnancy (at approximately 10-12 weeks of
      gestation) were analysed on 13,406 pairs of sisters who were either first-born or
      second-born (n=26,812). RESULTS: Early in pregnancy, first-born women were of BMI
      that was 0.57 kg/m(2) (2.4%) greater than their second-born sisters (p<0.0001).
      In addition, first-borns had greater odds of being overweight (OR 1.29; p<0.0001)
      or obese (OR 1.40; p<0.0001) than second-borns. First-borns were also negligibly
      taller (+1.2 mm) than their second-born sisters. Of note, there was a
      considerable increase in BMI over the 18-year period covered by this study, with
      an increment of 0.11 kg/m(2) per year (p<0.0001). CONCLUSIONS: Our study
      corroborates other large studies on men, and the steady reduction in family size
      may contribute to the observed increase in adult BMI worldwide.

PMID- 26311895
TI  - Novel Reassortant Human-Like H3N2 and H3N1 Influenza A Viruses Detected in Pigs
      Are Virulent and Antigenically Distinct from Swine Viruses Endemic to the United
      States.
AB  - Human-like swine H3 influenza A viruses (IAV) were detected by the USDA
      surveillance system. We characterized two novel swine human-like H3N2 and H3N1
      viruses with hemagglutinin (HA) genes similar to those in human seasonal H3
      strains and internal genes closely related to those of 2009 H1N1 pandemic
      viruses. The H3N2 neuraminidase (NA) was of the contemporary human N2 lineage,
      while the H3N1 NA was of the classical swine N1 lineage. Both viruses were
      antigenically distant from swine H3 viruses that circulate in the United States
      and from swine vaccine strains and also showed antigenic drift from human
      seasonal H3N2 viruses. Their pathogenicity and transmission in pigs were compared
      to those of a human H3N2 virus with a common HA ancestry. Both swine human-like
      H3 viruses efficiently infected pigs and were transmitted to indirect contacts,
      whereas the human H3N2 virus did so much less efficiently. To evaluate the role
      of genes from the swine isolates in their pathogenesis, reverse genetics
      generated reassortants between the swine human-like H3N1 virus and the seasonal
      human H3N2 virus were tested in pigs. The contribution of the gene segments to
      virulence was complex, with the swine HA and internal genes showing effects in
      vivo. The experimental infections indicate that these novel H3 viruses are
      virulent and can sustain onward transmission in pigs, and the naturally occurring
      mutations in the HA were associated with antigenic divergence from H3 IAV from
      humans and swine. Consequently, these viruses could have a significant impact on
      the swine industry if they were to cause more widespread outbreaks, and the
      potential risk of these emerging swine IAV to humans should be considered.
      IMPORTANCE: Pigs are important hosts in the evolution of influenza A viruses
      (IAV). Human-to-swine transmissions of IAV have resulted in the circulation of
      reassortant viruses containing human-origin genes in pigs, greatly contributing
      to the diversity of IAV in swine worldwide. New human-like H3N2 and H3N1 viruses
      that contain a mix of human and swine gene segments were recently detected by the
      USDA surveillance system. The human-like viruses efficiently infected pigs and
      resulted in onward airborne transmission, likely due to the multiple changes
      identified between human and swine H3 viruses. The human-like swine viruses are
      distinct from contemporary U.S. H3 swine viruses and from the strains used in
      swine vaccines, which could have a significant impact on the swine industry due
      to a lack of population immunity. Additionally, public health experts should
      consider an appropriate assessment of the risk of these emerging swine H3 viruses
      for the human population.

PMID- 26311897
TI  - Response to 'Place of death in the population dying from diseases indicative of
      palliative care need: a cross-national population-level study in 14 countries'.

PMID- 26311898
TI  - Associations between fruit and vegetable consumption and depressive symptoms:
      evidence from a national Canadian longitudinal survey.
AB  - BACKGROUND: Several cross-sectional studies have demonstrated associations
      between diet quality, including fruit and vegetable consumption, and mental
      health. However, research examining these associations longitudinally, while
      accounting for related lifestyle factors (eg, smoking, physical activity) is
      scarce. METHODS: This study used data from the National Population Health Survey
      (NPHS), a large, national longitudinal survey of Canadians. The sample included
      8353 participants aged 18 and older. Every 2 years from 2002/2003 to 2010/2011,
      participants completed self-reports of daily fruit and vegetable consumption,
      physical activity, smoking and symptoms of depression and psychological distress.
      Using generalised estimating equations, we modelled the associations between
      fruit and vegetable consumption at each timepoint and depression at the next
      timepoint, adjusting for relevant covariates. RESULTS: Fruit and vegetable
      consumption at each cycle was inversely associated with next-cycle depression
      (beta=-0.03, 95% CI -0.05 to -0.01, p<0.01) and psychological distress (beta=
      0.03, 95% CI -0.05 to -0.02, p<0.0001). However, once models were adjusted for
      other health-related factors, these associations were attenuated (beta=-0.01, 95%
      CI -0.04 to 0.02, p=0.55; beta=-0.00, 95% CI -0.03 to 0.02, p=0.78 for models
      predicting depression and distress, respectively). CONCLUSIONS: These findings
      suggest that relations between fruit and vegetable intake, other health-related
      behaviours and depression are complex. Behaviours such as smoking and physical
      activity may have a more important impact on depression than fruit and vegetable
      intake. Randomised control trials of diet are necessary to disentangle the
      effects of multiple health behaviours on mental health.

PMID- 26311900
TI  - Minimally invasive surgical Jarvik 2000 off-pump implantation.
AB  - Therapy with mechanical ventricular assist devices (VADs) in severe heart
      failure, open to discussion decades ago, is now well established for temporary or
      long-term support. The typical VAD candidate is very compromised and may not have
      sufficient resources to tolerate major surgical insults and trauma. Therefore,
      device implantation through smaller, less traumatic incisions is a desirable
      goal. The median sternotomy decreases lung volumes and reduces thoracic motion
      with a significant decrease in functional residual capacity and total lung
      capacity months later. Minimally invasive cardiac surgery was devised to reduce
      morbidity because of its potentially less inflammatory response, reduced
      transfusion requirements and minimal scarring with consequent rapid
      rehabilitation to normal life activity. Additionally, avoiding cardiopulmonary
      circulatory support (CPB) even for a short period might reduce the release of
      inflammatory cytokines and their consequences, as most CPB-related damage happens
      within the first few minutes. We describe the tricks and traps of minimally
      invasive approach during VAD implantation, by associating mini-anterior left
      thoracotomy in the fifth intercostal space with a mini-anterior right thoracotomy
      in the second intercostal space, without the aid of CPB in paravertebral block
      regional analgesia combined with mild general anasthesia.

PMID- 26311899
TI  - Machine Learning-based Classification of Diffuse Large B-cell Lymphoma Patients
      by Their Protein Expression Profiles.
AB  - Characterization of tumors at the molecular level has improved our knowledge of
      cancer causation and progression. Proteomic analysis of their signaling pathways
      promises to enhance our understanding of cancer aberrations at the functional
      level, but this requires accurate and robust tools. Here, we develop a state of
      the art quantitative mass spectrometric pipeline to characterize formalin-fixed
      paraffin-embedded tissues of patients with closely related subtypes of diffuse
      large B-cell lymphoma. We combined a super-SILAC approach with label-free
      quantification (hybrid LFQ) to address situations where the protein is absent in
      the super-SILAC standard but present in the patient samples. Shotgun proteomic
      analysis on a quadrupole Orbitrap quantified almost 9,000 tumor proteins in 20
      patients. The quantitative accuracy of our approach allowed the segregation of
      diffuse large B-cell lymphoma patients according to their cell of origin using
      both their global protein expression patterns and the 55-protein signature
      obtained previously from patient-derived cell lines (Deeb, S. J., D'Souza, R. C.,
      Cox, J., Schmidt-Supprian, M., and Mann, M. (2012) Mol. Cell. Proteomics 11, 77
      89). Expression levels of individual segregation-driving proteins as well as
      categories such as extracellular matrix proteins behaved consistently with known
      trends between the subtypes. We used machine learning (support vector machines)
      to extract candidate proteins with the highest segregating power. A panel of four
      proteins (PALD1, MME, TNFAIP8, and TBC1D4) is predicted to classify patients with
      low error rates. Highly ranked proteins from the support vector analysis revealed
      differential expression of core signaling molecules between the subtypes,
      elucidating aspects of their pathobiology. 

PMID- 26311901
TI  - TARM1 Is a Novel Leukocyte Receptor Complex-Encoded ITAM Receptor That
      Costimulates Proinflammatory Cytokine Secretion by Macrophages and Neutrophils.
AB  - We identified a novel, evolutionarily conserved receptor encoded within the human
      leukocyte receptor complex and syntenic region of mouse chromosome 7, named T
      cell-interacting, activating receptor on myeloid cells-1 (TARM1). The
      transmembrane region of TARM1 contained a conserved arginine residue, consistent
      with association with a signaling adaptor. TARM1 associated with the ITAM adaptor
      FcRgamma but not with DAP10 or DAP12. In healthy mice, TARM1 is constitutively
      expressed on the cell surface of mature and immature CD11b(+)Gr-1(+) neutrophils
      within the bone marrow. Following i.p. LPS treatment or systemic bacterial
      challenge, TARM1 expression was upregulated by neutrophils and inflammatory
      monocytes and TARM1(+) cells were rapidly recruited to sites of inflammation.
      TARM1 expression was also upregulated by bone marrow-derived macrophages and
      dendritic cells following stimulation with TLR agonists in vitro. Ligation of
      TARM1 receptor in the presence of TLR ligands, such as LPS, enhanced the
      secretion of proinflammatory cytokines by macrophages and primary mouse
      neutrophils, whereas TARM1 stimulation alone had no effect. Finally, an
      immobilized TARM1-Fc fusion protein suppressed CD4(+) T cell activation and
      proliferation in vitro. These results suggest that a putative T cell ligand can
      interact with TARM1 receptor, resulting in bidirectional signaling and raising
      the T cell activation threshold while costimulating the release of
      proinflammatory cytokines by macrophages and neutrophils. 

PMID- 26311904
TI  - Differential Requirements for L-Citrulline and L-Arginine during
      Antimycobacterial Macrophage Activity.
AB  - Microbicidal NO production is reliant on inducible NO synthase-mediated L
      arginine metabolism in macrophages (MPhis). However, L-arginine supply can be
      restricted by arginase activity, resulting in inefficient NO output and
      inhibition of antimicrobial MPhi function. MPhis circumvent this by converting L
      citrulline to L-arginine, thereby resupplying substrate for NO production. In
      this article, we define the metabolic signature of mycobacteria-infected murine
      MPhis supplied L-arginine, L-citrulline, or both amino acids. Using liquid
      chromatography-tandem mass spectrometry, we determined that L-arginine
      synthesized from L-citrulline was less effective as a substrate for arginase
      mediated L-ornithine production compared with L-arginine directly imported from
      the extracellular milieu. Following Mycobacterium bovis bacillus Calmette-Guerin
      infection and costimulation with IFN-gamma, we observed that MPhi arginase
      activity did not inhibit production of NO derived from L-citrulline, contrary to
      NO inhibition witnessed when MPhis were cultured in L-arginine. Furthermore, we
      found that arginase-expressing MPhis preferred L-citrulline over L-arginine for
      the promotion of antimycobacterial activity. We expect that defining the
      consequences of L-citrulline metabolism in MPhis will provide novel approaches
      for enhancing immunity, especially in the context of mycobacterial disease.

PMID- 26311903
TI  - Polymorphic HLA-C Receptors Balance the Functional Characteristics of KIR
      Haplotypes.
AB  - The human killer cell Ig-like receptor (KIR) locus comprises two groups of KIR
      haplotypes, termed A and B. These are present in all human populations but with
      different relative frequencies, suggesting they have different functional
      properties that underlie their balancing selection. We studied the genomic
      organization and functional properties of the alleles of the inhibitory and
      activating HLA-C receptors encoded by KIR haplotypes. Because every HLA-C
      allotype functions as a ligand for KIR, the interactions between KIR and HLA-C
      dominate the HLA class I-mediated regulation of human NK cells. The C2 epitope is
      recognized by inhibitory KIR2DL1 and activating KIR2DS1, whereas the C1 epitope
      is recognized by inhibitory KIR2DL2 and KIR2DL3. This study shows that the
      KIR2DL1, KIR2DS1, and KIR2DL2/3 alleles form distinctive phylogenetic clades that
      associate with specific KIR haplotypes. KIR A haplotypes are characterized by
      KIR2DL1 alleles that encode strong inhibitory C2 receptors and KIR2DL3 alleles
      encoding weak inhibitory C1 receptors. In striking contrast, KIR B haplotypes are
      characterized by KIR2DL1 alleles that encode weak inhibitory C2 receptors and
      KIR2DL2 alleles encoding strong inhibitory C1 receptors. The wide-ranging
      properties of KIR allotypes arise from substitutions throughout the KIR molecule.
      Such substitutions can influence cell surface expression, as well as the avidity
      and specificity for HLA-C ligands. Consistent with the crucial role of inhibitory
      HLA-C receptors in self-recognition, as well as NK cell education and response,
      most KIR haplotypes have both a functional C1 and C2 receptor, despite the
      considerable variation that occurs in ligand recognition and surface expression. 

PMID- 26311902
TI  - The Blood Transcriptome of Experimental Melioidosis Reflects Disease Severity and
      Shows Considerable Similarity with the Human Disease.
AB  - Melioidosis, a severe human disease caused by the bacterium Burkholderia
      pseudomallei, has a wide spectrum of clinical manifestations ranging from acute
      septicemia to chronic localized illness or latent infection. Murine models have
      been widely used to study the pathogenesis of infection and to evaluate novel
      therapies or vaccines, but how faithfully they recapitulate the biology of human
      melioidosis at a molecular level is not known. In this study, mice were
      intranasally infected with either high or low doses of B. pseudomallei to
      generate either acute, chronic, or latent infection and host blood and tissue
      transcriptional profiles were generated. Acute infection was accompanied by a
      homogeneous signature associated with induction of multiple innate immune
      response pathways, such as IL-10, TREM1, and IFN signaling, largely found in both
      blood and tissue. The transcriptional profile in blood reflected the
      heterogeneity of chronic infection and quantitatively reflected the severity of
      disease. Genes associated with fibrosis and tissue remodeling, including matrix
      metalloproteases and collagen, were upregulated in chronically infected mice with
      severe disease. Transcriptional signatures of both acute and chronic melioidosis
      revealed upregulation of iNOS in tissue, consistent with the expression of IFN
      gamma, but also Arginase-1, a functional antagonist of the iNOS pathway, and was
      confirmed by immunohistochemistry. Comparison of these mouse blood datasets by
      pathway and modular analysis with the blood transcriptional signature of patients
      with melioidosis showed that many genes were similarly perturbed, including
      Arginase-1, IL-10, TREM1, and IFN signaling, revealing the common immune response
      occurring in both mice and humans. 

PMID- 26311906
TI  - Using shared genetic controls in studies of gene-environment interactions.
AB  - With the advent of modern genomic methods to adjust for population
      stratification, the use of external or publicly available controls has become an
      attractive option for reducing the cost of large-scale case-control genetic
      association studies. In this article, we study the estimation of joint effects of
      genetic and environmental exposures from a case-control study where data on
      genome-wide markers are available on the cases and a set of external controls
      while data on environmental exposures are available on the cases and a set of
      internal controls. We show that under such a design, one can exploit an
      assumption of gene-environment independence in the underlying population to
      estimate the gene-environment joint effects, after adjustment for population
      stratification. We develop a semiparametric profile likelihood method and related
      pseudolikelihood and working likelihood methods that are easy to implement in
      practice. We propose variance estimators for the methods based on asymptotic
      theory. Simulation is used to study the performance of the methods, and data from
      a multi-centre genome-wide association study of bladder cancer is further used to
      illustrate their application.

PMID- 26311905
TI  - PI3Kdelta Regulates the Magnitude of CD8+ T Cell Responses after Challenge with
      Listeria monocytogenes.
AB  - PI3Ks regulate diverse immune cell functions by transmitting intracellular
      signals from Ag, costimulatory receptors, and cytokine receptors to control cell
      division, differentiation, survival, and migration. In this study, we report the
      effect of inhibiting the p110delta subunit of PI3Kdelta on CD8(+) T cell
      responses to infection with the intracellular bacteria Listeria monocytogenes. A
      strong dependency on PI3Kdelta for IFN-gamma production by CD8(+) T cells in
      vitro was not recapitulated after Listeria infection in vivo. Inactivation of
      PI3Kdelta resulted in enhanced bacterial elimination by the innate immune system.
      However, the magnitudes of the primary and secondary CD8 +: T cell responses were
      reduced. Moreover, PI3Kdelta activity was required for CD8(+) T cells to provide
      help to other responding CD8(+) cells. These findings identify PI3Kdelta as a key
      regulator of CD8(+) T cell responses that integrates extrinsic cues, including
      those from other responding cells, to determine the collective behavior of CD8(+)
      T cell populations responding to infection. 

PMID- 26311907
TI  - The effectiveness of corticosteroid injection in the treatment of plantar
      fasciitis.
AB  - Plantar fasciitis is a common cause of heel pain in adults. Although it is
      usually a self-limiting condition, the pain may become prolonged and severe
      enough to cause significant distress and disruption to the patient's daily
      activities and work. PubMed and Cochrane Central Register of Controlled Trials
      databases were searched for randomised controlled trials (RCTs) and a total of
      ten RCTs were selected for evaluation. These RCTs involved the use of either
      palpation- or ultrasonography-guided corticosteroid injections in patients
      diagnosed with plantar fasciitis. All placebo-controlled RCTs showed a
      significant reduction in pain with the use of corticosteroid injections. Some
      studies also showed that corticosteroid injections yielded better results than
      other treatment modalities. However, it is evident from these studies that the
      effects of corticosteroid injections are usually short-term, lasting 4-12 weeks
      in duration. Complications such as plantar fascia rupture are uncommon, but
      physicians need to weigh the treatment benefits against such risks. 

PMID- 26311908
TI  - PILL Series. Vitamin D deficiency.
AB  - Vitamin D deficiency is common and may contribute to osteopenia, osteoporosis and
      falls risk in the elderly. Screening for vitamin D deficiency is important in
      high-risk patients, especially for patients who suffered minimal trauma
      fractures. Vitamin D deficiency should be treated according to the severity of
      the deficiency. In high-risk adults, follow-up serum 25-hydroxyvitamin D
      concentration should be measured 3-4 months after initiating maintenance therapy
      to confirm that the target level has been achieved. All patients should maintain
      a calcium intake of at least 1,000 mg for women aged <= 50 years and men <= 70
      years, and 1,300 mg for women > 50 years and men > 70 years. 

PMID- 26311909
TI  - Imaging of acute cholecystitis and cholecystitis-associated complications in the
      emergency setting.
AB  - Acute cholecystitis is a common cause of right upper quadrant pain in patients
      presenting at the emergency department. Early diagnosis and recognition of
      associated complications, though challenging, are essential for timely
      management. Imaging studies, including ultrasonography, computed tomography and
      magnetic resonance imaging, are increasingly utilised for the evaluation of
      suspected cases of cholecystitis. These investigations help in diagnosis,
      identification of complications and surgical planning. Imaging features of acute
      cholecystitis have been described in the literature and are variable, depending
      on the stage of inflammation. This article discusses the spectrum of
      cholecystitis-associated complications and their imaging manifestations. We also
      suggest a checklist for the prompt and accurate identification of complications
      in acute cholecystitis. 

PMID- 26311910
TI  - Implementation of an obstetric cell salvage service in a tertiary women's
      hospital.
AB  - INTRODUCTION: Intraoperative cell salvage (ICS) is an important aspect of patient
      blood management programmes. An ICS service was introduced at KK Women's and
      Children's Hospital, Singapore, from 2 May 2011 to 30 April 2013 to aid in the
      management of massive obstetric haemorrhage. METHODS: With support from the
      Ministry of Health's Healthcare Quality Improvement and Innovation Fund, a
      workgroup comprising obstetricians, anaesthetists and nursing staff was formed to
      develop training requirements, clinical guidelines and protocols for implementing
      ICS using the Haemonetics Cell Saver 5. Pregnant women with an anticipated blood
      loss of > 1,000 mL during Caesarean delivery, a baseline haemoglobin level of <
      10 g/dL, rare blood types and who had refused donor blood were recruited to the
      service after obtaining informed consent. RESULTS: A total of 11 women were
      recruited to the ICS service; the primary indications were placenta praevia and
      placenta accreta. Median blood loss in these 11 patients was 1,500 (range 400
      3,000) mL. In four patients, adequate autologous blood was collected to initiate
      processing and salvaged, processed blood was successfully reinfused (mean 381.3
      [range 223.0-700.0] mL). Median blood loss among these four patients was 2,000
      (range 2,000-3,000) mL. No adverse event occurred following autologous
      transfusion. Mean immediate postoperative haemoglobin level was 8.0 (range 7.1
      9.4) g/dL. CONCLUSION: The implementation of an obstetric ICS service in our
      institution was successful. Future studies should seek to address the cost
      effectiveness of ICS in reducing allogeneic blood utilisation.

PMID- 26311911
TI  - Infant lumbar and thoracic epidurals for abdominal surgeries: cases in a
      paediatric tertiary institution.
AB  - INTRODUCTION: There is strong evidence that epidural analgesia provides good
      postoperative pain relief in adults, but its use in infants is less established.
      In this retrospective study, we present our experience with managing infant
      epidural analgesia for abdominal surgeries in a tertiary paediatric institution.
      METHODS: The records of 54 infants who had received a thoracic or lumbar epidural
      as perioperative analgesia for abdominal surgeries were included. The mean age of
      the infants was 6.1 (standard deviation [SD] 3.8) months and their mean weight
      was 6.8 kg (SD 1.8). Most (63%) had an ASA (American Society of
      Anesthesiologists) status of 2 and all underwent elective gastrointestinal,
      urogenital, hepatobiliary or retroperitoneal surgeries. 20 catheters (37.0%) were
      inserted in the thoracic region and 33 (61.1%) in the lumbar region. RESULTS: A
      total of 52 (96.3%) catheters provided adequate intraoperative analgesia and 36
      (66.7%) provided effective analgesia for the postoperative period. Active
      management of epidural analgesia, such as through epidural top-ups and infusion
      rate adjustment, was necessary to optimise analgesia in 22 (44%) of the 50
      patients postoperatively. Reasons for premature catheter removal were mainly
      technical issues such as catheter disconnection, leakage and blockage.
      CONCLUSION: Our data suggests that in experienced hands, specialised settings and
      active management, the success rate of epidural analgesia in infants undergoing
      major abdominal surgeries is high and without major incident.

PMID- 26311912
TI  - The 'clamshell' approach to emergency department thoracotomy.

PMID- 26311913
TI  - Phaeochromocytoma presenting with pseudo-intestinal obstruction and lactic
      acidosis.
AB  - Phaeochromocytomas are rare neuroendocrine tumours with variable clinical signs
      and symptoms. Hypertension, tachycardia, sweating and headaches are cardinal
      manifestations. Although nausea and abdominal pain are the more common
      gastrointestinal features, rare gastrointestinal spectrums have been reported
      that can mimic abdominal emergencies. Metabolic effects of hypercatecholaminaemia
      are vast and one such rare presentation is lactic acidosis. We describe a case of
      phaeochromocytoma presenting with both intestinal pseudo-obstruction as well as
      lactic acidosis. This case report highlights the importance of having a high
      index of suspicion for and early recognition of the gastrointestinal and
      metabolic manifestations of phaeochromocytomas. 

PMID- 26311914
TI  - Vaginal metastasis presenting as postmenopausal bleeding.
AB  - Vaginal cancer is rare worldwide and represents 2% of all gynaecological cancers
      in Singapore. Primary vaginal malignancies are rare and vaginal metastases
      constitute the majority of vaginal malignancies. Most of these metastases arise
      from the cervix, endometrium or ovary, although they can also metastasise from
      distant sites such as the colon, breast and pancreas. We report a rare case of
      vaginal metastasis in a patient with previous gastric and rectal adenocarcinomas.
      An 89-year-old woman with a history of gastric and rectal malignancy presented
      with postmenopausal bleeding. A 2-cm vaginal tumour at the introitus was
      discovered upon examination. This case demonstrates the importance of performing
      a gynaecological examination during follow-up for patients with a history of
      malignancy. The prognosis for vaginal metastasis is poor, as it is often
      associated with disseminated disease. Depending on the extent of the lesions,
      radiotherapy or surgery can be considered. 

PMID- 26311915
TI  - Isolation of multidrug-resistant Salmonella in Singapore.
AB  - Multidrug-resistant Salmonella is a well-recognised problem worldwide, especially
      in developing countries such as India, where non-typhoidal Salmonella infections
      and enteric fever are endemic. Antimicrobial resistance, particularly to
      fluoroquinolones, is common and leads to the frequent use of alternative agents,
      such as azithromycin. We herein describe the first reported case of azithromycin
      resistant Salmonella gastroenteritis in a Singaporean patient. 

PMID- 26311916
TI  - Global-scale seasonally resolved black carbon vertical profiles over the Pacific.
AB  - [1] Black carbon (BC) aerosol loadings were measured during the High-performance
      Instrumented Airborne Platform for Environmental Research Pole-to-Pole
      Observations (HIPPO) campaign above the remote Pacific from 85 degrees N to 67
      degrees S. Over 700 vertical profiles extending from near the surface to max ~14
      km altitude were obtained with a single-particle soot photometer between early
      2009 and mid-2011. The data provides a climatology of BC in the remote regions
      that reveals gradients of BC concentration reflecting global-scale transport and
      removal of pollution. BC is identified as a sensitive tracer of extratropical
      mixing into the lower tropical tropopause layer and trends toward surprisingly
      uniform loadings in the lower stratosphere of ~1 ng/kg. The climatology is
      compared to predictions from the AeroCom global model intercomparison initiative.
      The AeroCom model suite overestimates loads in the upper troposphere/lower
      stratosphere (~10*) more severely than at lower altitudes (~3*), with bias
      roughly independent of season or geographic location; these results indicate that
      it overestimates BC lifetime.

PMID- 26311917
TI  - An experimental and theoretical view of energetic C60 cluster bombardment onto
      molecular solids.
AB  - Recent experimental measurements and calculations performed by molecular dynamics
      computer simulations indicate, for highly energetic C60 primary ions bombarding
      molecular solids, the emission of intact molecules is unique. An energy- and
      angle-resolved neutral mass spectrometer coupled with laser photoionization
      techniques was used to measure the polar angle distribution of neutral
      benzo[a]pyrene molecules desorbed by 20-keV [Formula: see text] primary ions and
      observed to peak at off-normal angles integrated over all possible emission
      energies. Similarly, computer simulations of 20-keV C60 projectiles bombarding a
      coarse-grained benzene system resulted in calculations of nearly identical polar
      angle distributions. Upon resolving the measured and calculated polar angle
      distributions, sputtered molecules with high kinetic energies are the primary
      contributors to the off-normal peak. Molecules with low kinetic energies were
      measured and calculated to desorb broadly peaked about the surface normal. The
      computer simulations suggest the fast deposition of energy from the C60 impact
      promotes the molecular emission by fluid-flow and effusive-type motions. The
      signature of off-normal emission angles is unique for molecules because
      fragmentation processes remove molecules that would otherwise eject near normal
      to the surface. Experimental measurements from a Ni {001} single crystal
      bombarded by 20-keV [Formula: see text] demonstrate the absence of this unique
      signature.

PMID- 26311918
TI  - A Note on Evaluation of Temporal Derivative of Hypersingular Integrals over Open
      Surface with Propagating Contour.
AB  - The short note concerns with elasticity problems involving singular and
      hypersingular integrals over open surfaces, specifically cracks, with the contour
      propagating in time. Noting that near a smooth part of a propagating contour the
      state is asymptotically plane, we focus on 1D hypersingular integrals and employ
      complex variables. By using the theory of complex variable singular and
      hypersingular integrals, we show that the rule for evaluation of the temporal
      derivative is the same as that for proper integrals. Being applied to crack
      problems the rule implies that the temporal derivative may be evaluated by
      differentiation under the integral sign.

PMID- 26311919
TI  - Activity performance problems of patients with cardiac diseases and their impact
      on quality of life.
AB  - [Purpose] To describe the functional consequences of patients with cardiac
      diseases and analyze associations between activity limitations and quality of
      life. [Subjects and Methods] Seventy subjects (mean age: 60.1+/-12.0 years) were
      being treated by Physical Medicine and Rehabilitation and Cardiology Departments
      were included in the study. Activity limitations and participation restrictions
      as perceived by the individual were measured by the Canadian Occupational
      Performance Measure (COPM). The Nottingham Extended Activities of Daily Living
      (NEADL) Scale was used to describe limitations in daily living activities. To
      detect the impact of activity limitations on quality of life the Nottingham
      Health Profile (NHP) was used. [Results] The subjects described 46 different
      types of problematic activities. The five most identified problems were walking
      (45.7%), climbing up the stairs (41.4%), bathing (30%), dressing (28.6%) and
      outings (27.1%). The associations between COPM performance score with all
      subgroups of NEADL and NHP; total, energy, physical abilities subgroups, were
      statistically significant. [Conclusion] Our results showed that patients with
      cardiac diseases reported problems with a wide range of activities, and that also
      quality of life may be affected by activities of daily living. COPM can be
      provided as a patient-focused outcome measure, and it may be a useful tool for
      identifying those problems. 

PMID- 26311920
TI  - The effects of four weeks aerobic training on saliva cortisol and testosterone in
      young healthy persons.
AB  - [Purpose] The purpose of this study was to evaluate the effect of 4 weeks
      moderate aerobic exercise on outcome measures of saliva stress hormones and
      lactate levels in healthy adult volunteers. [Subjects and Methods] Sixteen
      healthy students with an age range of 15-25 years participated in this study. The
      participants performed an exercise test of moderate intensity for 4 weeks, three
      times per week. The exercise was treadmill walking. Saliva concentrations of
      cortisol, testosterone and lactate dehydrogenase (LDH) were measured before and
      after the 4 weeks of moderate aerobic training using immunoassay techniques.
      [Results] After 4 weeks of exercise, there were significant increases in
      cortisol, free testosterone levels, and LDH activity along with a significant
      decrease in the ratios between testosterone and cortisol levels. No significant
      correlations were found among the studied parameters in the resting stage, a
      result which supports the positive effect of exercise on stress hormones
      following 4 weeks of training. [Conclusion] The results suggest that four weeks
      exercise of moderate intensity significantly affects the salivary stress hormones
      of young healthy volunteers. The data support the importance of salivary stress
      hormones as potential biological markers especially for older ages. However, more
      research is required to validate these biological markers which determine the
      host response to physical activity. 

PMID- 26311921
TI  - Effectiveness of a back care pillow as an adjuvant physical therapy for chronic
      non-specific low back pain treatment: a randomized controlled trial.
AB  - [Purpose] The aim of this study was to investigate the effect of a back care
      pillow (BCP) on pain, lumbar range of motion (LROM) and functional disability of
      patients with chronic non-specific low back pain (LBP). [Subjects and Methods]
      Fifty-two subjects who were aged between 20-69 years old, who presented with LBP
      of more than 3 months duration with a numerical rating scale (NRS) value of at
      least 4 were randomly assigned to treatment (BCP) and control (CON) groups.
      Participants in each group received six sessions of the 30 minutes treatment for
      two weeks. The BCP group was asked to wear the BCP during the daytime during the
      study period. Pain, lumbar ROM and functional disability were assessed before and
      after the 2-week treatment, and at the end of a 12-week follow up. [Results]
      After the 2-week treatment and 12-week follow up, all outcomes had improved in
      both groups; the BCP group had maintained the decrease in pain intensity and
      improved lumbar ROM in the extension position after the 12-week follow up, and
      showed better improvements in all outcomes at 2 weeks and after the 12-week
      follow up. [Conclusion] BCP combined with physical therapy had better pain,
      lumbar ROM and functional disability outcomes than physical therapy alone. 

PMID- 26311922
TI  - Association of physical activity and health status with intelligence quotient of
      high school students in Jeddah.
AB  - [Purpose] The present study investigated the relationships of physical activity
      and healthiness with the intelligence quotients of high school students in
      Jeddah. [Subjects and Methods] A total of 135 male and female students were
      randomly drawn from public and private secondary schools in Jeddah. A self
      designed questionnaire was distributed to the students that included demographic,
      physical activity, and health status sections. Body mass index measurement and an
      intelligence quotient test were carried out for all students. In addition,
      samples of blood were collected to estimate hemoglobin and serum iron. [Results]
      The highest proportions of males and females (39.1% and 51% respectively) had an
      intelligence quotient score of more than 75%. Moreover, the findings revealed
      that about 35% of the students were categorized as overweight obesity, and there
      was aninverse correlation between body mass index and physical activity. Students
      who shared physical education classes and exercising at and outside school showed
      a positive correlation with high IQ scores. Regarding hemoglobin and iron levels,
      there were significant correlations between their levels in blood and IQ.
      [Conclusion] The intelligence quotient of adolescent students is positively
      associated with physical activity and health status. 

PMID- 26311923
TI  - Physical activity and environmental influences on adrenal fatigue of Saudi
      adults: biochemical analysis and questionnaire survey.
AB  - [Purpose] This research work was performed to examine whether different levels of
      physical activity and environmental and social factors are associated with
      changes in adrenal hormones as markers of adrenal fatigue in Saudi adult
      volunteers. [Subjects and Methods] A total of 160 Saudi adults aged 15-22 years
      were included in this study. The adrenal fatigue score, sociodemographic
      attributes, and the level of physical activity were evaluated via pre-validated
      internet-based questionnaire surveys. Adrenal hormones such as ACTH and cortisol
      were measured using immunoassay techniques. [Results] Significant increases in
      the levels of ACTH and cortisol biomarkers were found in the participants with
      moderate to severe fatigue scores, poor environmental factors, and low physical
      activity. However, in physically active participants, significant decreases in
      ACTH and cortisol levels were found with remarkable improvement in adrenal
      fatigue status. The decrement in adrenal hormonal levels positively correlated
      (r= 0.976) with the improvement in adrenal fatigue status in the physically
      active participants. [Conclusion] Our results suggest that the level of physical
      activity and environmental and social factors differentially influence the
      adrenal fatigue status via changes in the levels of adrenal hormones. Also, ACTH
      and cortisol biomarkers may be useful as markers measuring the severity of
      adrenal fatigue. 

PMID- 26311924
TI  - Effects of early physiotherapy with respect to severity of pneumonia of elderly
      patients admitted to an intensive care unit: a single center study in Japan.
AB  - [Purpose] We performed early physiotherapy for elderly patients with pneumonia
      admitted to an intensive care unit (ICU), and examined the effects of this early
      physiotherapy on the severity of pneumonia. [Subjects and Methods] Patients for
      whom physiotherapy was started the day after admission to the ICU (acute phase)
      were assigned to the early intervention group and compared with patients in the
      standard intervention group. All patients were divided into three groups (Groups
      I, II, and III) based on the severity of pneumonia. We evaluated the ICU
      admission period, hospitalization period, and activities of daily living (ADL)
      before and after admission. [Results] With respect to the severity of pneumonia,
      Group II showed significant differences in the ICU admission period and rates of
      change in the operating range, cognitive domain, and Functional Independence
      Measure (FIM). Group III showed significant differences in the ICU admission
      period and rate of change in the cognitive domain (FIM item). The results were
      more favorable in the early intervention group than in the standard intervention
      group. [Conclusion] The ICU admission period was shorter and a reduction in the
      ADL level was prevented in Groups II, and III compared to Group I. This may have
      occurred because of the early rehabilitation. 

PMID- 26311925
TI  - Effect of virtual reality games on stroke patients' balance, gait, depression,
      and interpersonal relationships.
AB  - [Purpose] The purpose of the study was to determine the effects of training using
      virtual reality games on balance and gait ability, as well as the psychological
      characteristics of stroke patients, such as depression and interpersonal
      relationships, by comparing them with the effects of ergometer training.
      [Subjects] Forty stroke patients were randomly divided into a virtual reality
      group (VRG, N = 20) and an ergometer training group (ETG, N = 20). [Methods] VRG
      performed training using the Xbox Kinect. ETG performed training using an
      ergometer bicycle. Both groups received training 30 min per day, five times per
      week, for eight weeks. [Results] Both the VRG and ETG subjects exhibited a
      significant difference in weight distribution ratio on the paralyzed side and
      balance ability. Both the VRG and ETG patients showed significant improvement in
      psychological measures BDI and RCS, after the intervention, and the VRG sowed a
      more significant increase in BDI than the ETG. [Conclusion] According to the
      result of this study, virtual reality training and ergometer training were both
      effective at improving balance, gait abilities, depression, and interpersonal
      relationships among stroke patients. 

PMID- 26311926
TI  - The effects of a community-centered muscle strengthening exercise program using
      an elastic band on the physical abilities and quality of life of the rural
      elderly.
AB  - [Purpose] The purpose of this study was to examine the effects of a muscle
      strengthening exercise program using an elastic band on changes in the physical
      abilities and quality of life of the rural elderly. [Subjects] The subjects of
      this study were 46 elderly people (8 males, 38 females) aged 65 or older, who
      lived in a rural area and managed their daily lives independently. [Methods] The
      study's exercise program was conducted 16 times for 80 minutes each session over
      an eight-week period. This program consisted of several exercises to strengthen
      muscular endurance and improve balance ability based on exercises using Thera
      bands. The physical abilities of the subjects were divided into muscular
      endurance, upper-extremity flexibility, balance, and low-extremity agility. Each
      ability was measured to compare the effects of the exercise program. In addition,
      the Korean version of the World Health Organization Quality of Life (WHOQOL)-BREF
      questionnaire was used to examine changes in the subjects' quality of life.
      [Results] The subjects showed improvements in muscular endurance, balance, and
      low-extremity agility. They also exhibited an overall statistically significant
      improvement in quality of life scores after the exercise program. In terms of the
      main items, changes were observed in the areas of psychological relations, social
      relations, and environment. [Conclusion] The community-centered muscle
      strengthening exercise program using the elastic band was found to improve
      muscular endurance, balance, agility, and quality of life of rural elderly
      subjects. 

PMID- 26311927
TI  - Effects of experience-based group therapy on cognitive and physical functions and
      psychological symptoms of elderly people with mild dementia.
AB  - [Purpose] The purpose of this study was to investigate the effect of experience
      based group therapy consisting of cooking and physical activities for elderly
      people with mild dementia on their cognitive and physical function, as well as on
      their psychological symptoms. [Subjects] The subjects of this study were 12 older
      adults with mild dementia (3 males, 9 females; 76.75 +/- 3.61 years) who
      voluntarily consented to participate in the study. [Methods] In total, 12
      subjects received experience-based group therapy for 2 hours per session once per
      week, totaling 10 sessions. Cognitive function was evaluated using the Mini
      Mental State Examination-Korean (MMSE-K), and physical function was evaluated
      using the Geriatric Physical health condition measurement Tool (GPT). The
      Geriatric Depression Scale Korean Version (GDS-K) and Geriatric Quality of Life
      Dementia (GQOL-D) were used to measure psychological symptoms. [Results] There
      were significant differences between the MMSE-K, GPT, GDS-K, and GQOL-D scores of
      before and after group therapy. [Conclusion] In conclusion, it is regarded that
      cognitive function, physical function, and psychological health improved through
      experience-based group therapy. 

PMID- 26311928
TI  - The effects of prone bridge exercise on trunk muscle thickness in chronic low
      back pain patients.
AB  - [Purpose] This study aimed to investigate the effects of prone bridge exercise on
      trunk muscle thickness. [Subjects and Methods] Thirty-seven chronic low back pain
      patients participated in this study. Each participant was randomly assigned to
      one of three exercise groups, namely, a prone bridge exercise group, supine
      bridge exercise on a Swiss ball group, and supine bridge exercise group. The
      thicknesses of the transverse abdominis (TrA), internal oblique (IO), and
      external oblique (EO) were measured using ultrasound. [Results] After eight weeks
      of training, the three groups showed significant increases in the thicknesses of
      the TrA, IO, and EO. Among the groups, TrA and IO showed significantly different
      muscle thicknesses. [Conclusion] The prone bridge exercise significantly affected
      the thicknesses of the TrA, IO, and EO unlike the supine bridge exercises. Based
      on the results of this study, the prone bridge exercise is a more effective
      method to improve trunk stability than conventional supine bridge exercises. 

PMID- 26311929
TI  - A clinical study of the rotational alignment of the femoral component in total
      knee arthroplasty.
AB  - [Purpose] The reasons for femorotibial rotational malalignment after total knee
      arthroplasty (TKA) were analyzed to provide evidence for clinical knee joint
      surgery and to reduce complications. [Subjects and Methods] Ninety knees of 60
      patients were selected and randomly divided into two groups (n=30). For one
      group, rotational alignment of the femoral component was determined by the
      transepicondylar axis and TKA was performed. For the other group, rotational
      alignment of the femoral component was conducted through 3 degrees  external
      rotation of the posterior femoral condyles. Knee joint specimens were operated
      with TKA and various biomechanical indices were measured. [Results] The femoral
      epicondylar axis was a constant, reliable reference for femoral component
      rotational alignment. When the femoral component was rotated by 0 degrees  versus
      the epicondylar axis, the peak contact pressure on the patellofemoral joint was
      optimal. When the femoral component was arranged in parallel with Whiteside's
      line, the peak contact pressure on the patellofemoral joint varied largely. The
      patellofemoral contact areas of the two groups were similar. [Conclusion] Axial
      rotational alignment of the femoral component influenced the contact pressure of
      patellofemoral joints in TKA more significantly than external rotation of the
      femoral condyles. It is more reliable to use the femoral epicondylar axis as the
      reference for the rotational alignment of the femoral component. 

PMID- 26311930
TI  - The relationship between fracture and quality of life in Korean adults receiving
      treatment for osteoporosis based on the 2010 Korean Community Health Survey.
AB  - [Purpose] The purpose of this study was to investigate the relationship between
      fracture and quality of life in Korean adults receiving treatment for
      osteoporosis based on the 2010 Korean Community Health Survey (KCHS). [Subjects
      and Methods] This study utilized the raw data of the 2010 KCHS. In the survey,
      osteoporosis was assessed in 228,903 subjects, excluding 326 for whom there was
      insufficient data. There were 17,387 subjects with osteoporosis confirmed by a
      doctor's diagnosis and 9,419 of them were being treated for osteoporosis at the
      time of the survey. [Results] Among the patients being treated, those with
      fractures had a significantly lower QOL than patients who did not experience
      fractures. The lower QOL scores were caused by hip, vertebral and wrist
      fractures, and in all cases, QOL was significantly lower. Greater numbers of
      fractures significantly lowered QOL scores compared to participants without
      fractures. [Conclusion] Fractures in patients receiving treatment for
      osteoporosis have a direct impact on QOL. Among the different types of fractures,
      hip fractures resulted in the lowest scores. Therefore, to avoid additional
      fractures caused by inappropriate management of osteoporosis, we suggest that
      there is a need to improve fall related self-efficacy and prevention programs. 

PMID- 26311931
TI  - Effect of ankle kinesio taping on vertical jump with run-up and countermovement
      jump in athletes with ankle functional instability.
AB  - [Purpose] Limited research has been performed in spite of biomechanical
      evaluation of jump landing with kinesio taping. Therefore, the main objective of
      this study was to evaluate the effect of kinesio taping applied to athletes. In
      this study, the authors wished to investigate the effect of kinesio taping during
      a vertical jump with run-up and countermovement jump on ankle functional
      instability. [Subjects and Methods] Ten male athletes with ankle functional
      instability (FI) were recruited in this study from a college volleyball team.
      Each participant was requested to perform two tasks, the countermovement jump and
      vertical jump with run-up. Infrared high-speed cameras and force plates were used
      to assess the effect of ankle taping. [Results] The results showed that the peak
      ground reaction force in the sagittal plane during a vertical jump with run-up
      slowed down after kinesio taping and that the peak ankle plantar flexion moment
      in both types of jump also decreased. [Conclusion] In conclusion, this study
      proved the effect of kinesio taping on ankle functional instability, which was
      evaluated by measuring the vertical ground reaction force and peak plantar
      flexion moment. Its finding may allow us to provide some recommendations for
      athletes and trainers. 

PMID- 26311932
TI  - Clinical physical therapists research activity reality and barriers to their
      utilizing research findings.
AB  - [Purpose] This research study was performed to investigate the barriers to using
      the research findings of physical therapists on evidence-based practice.
      [Subjects] The subjects of this research were physical therapists employed by
      hospitals that agreed to cooperate with the research in B city. [Methods] A
      questionnaire made up of 6 research items, 8 physical therapist items, 6
      presentation items, and 8 setting items, for a total of 28 items, was
      distributed. The responses were scored so the higher result scores indicate a
      higher barrier level to using research findings. Differences in barrier levels
      related to the likelihood of therapists using research findings in their practice
      varied according to the general characteristics of the result as according to the
      t-test and ANOVA. Scheffe's test was used as a post hoc test. [Results] The
      analysis of 158 returned questionnaires revealed that there were significant
      relationships between the age, educational level, and professional satisfaction
      of the therapists and the barriers to using research finding. Significant
      relationships were also found between the items of "Research participation in
      clinical research", "Frequency of reading research articles", and "Support of
      manager to use research" and the barrier level. No relationship was demonstrated
      between the recognition level of evidence-based practice and the performance
      level with the barrier score to using research findings. [Conclusion] This study
      demonstrated that to improve the utilization of research findings, there is a
      need to provide therapists with continual education and opportunities to
      participate in research, and environments and ways in which the research results
      can be given practical applications. 

PMID- 26311933
TI  - The effect of single extremity-vibration on the serum sclerostin level.
AB  - [Purpose] Sclerostin is mechanosensitive protein that is produced exclusively by
      osteocytes. It was reported that the plasma sclerostin level increases in the
      10th minute after the application of Whole-Body Vibration. The aim of this study
      was to determine whether single extremity-vibration induces any change in the
      serum sclerostin level. [Subjects and Methods] Eight healthy young-adult
      volunteers were recruited for this pilot study. The participants sat on a chair
      with their left hip and knee joints flexed at 90 degrees. The lower leg was
      exposed to vibration: 40 Hz, 4 mm, 60 s. Blood samples were collected before and
      after the vibration. The serum sclerostin levels were blindly measured in dual
      controlled blood samples. [Results] The serum sclerostin level before vibration
      was 328.2+/-589.9 pg/ml, and it showed no significant change after vibration.
      [Conclusion] Unlike Whole-Body Vibration, Single-Extremity Vibration did not
      affect the serum sclerostin level significantly. This finding can be explained by
      the limited bone volume exposed to vibration. Bone volume exposed to vibration is
      less during Single-Extremity Vibration than during Whole-Body Vibration. 

PMID- 26311934
TI  - Effects of Hatha yoga exercise on plasma malondialdehyde concentration and
      superoxide dismutase activity in female patients with shoulder pain.
AB  - [Purpose] The purpose of this study was to analyze the effects of Hatha yoga
      exercise on plasma malondialdehyde (MDA) concentration and superoxide dismutase
      (SOD) activity in female patients with shoulder pain. [Subjects] Subjects
      comprised 20 female patients with shoulder pain. [Methods] Subjects were divided
      into 2 groups: a Hatha yoga exercise group (n = 10) and a control group that
      performed no exercise (n = 10). The subjects' body composition, plasma
      malondialdehyde concentrations, and superoxide dismutase activities were measured
      before and after a 16-week Hatha yoga exercise program. [Results] After the 16
      week Hatha yoga exercise program, the exercise group had significantly lower
      plasma MDA concentrations than the control group. In addition, the exercise group
      had significantly higher plasma SOD activity than the control group.
      [Conclusions] Hatha yoga exercise improves flexibility, muscle tone and strength,
      balance, and joint function. Our findings indicate that regular and continuous
      yoga exercise effectively improved body composition, decrease plasma MDA
      concentration, and increase plasma SOD activity in female patients with shoulder
      pain. 

PMID- 26311935
TI  - The effect of the correlation between the contraction of the pelvic floor muscles
      and diaphragmatic motion during breathing.
AB  - [Purpose] This study was conducted to investigate the effect of the correlation
      between the pelvic floor muscles (PFM) and diaphragmatic motion during breathing.
      [Subjects] The subjects of this study were 20 healthy female students who
      listened to an explanation of the study methods, purpose and agreed to
      participate in the experiment. [Methods] Radiograph equipment was used to examine
      diaphragmatic motion with contraction of the PFM during breathing, and a
      spirometer was used to examine lung vital capacity. [Results] The results
      revealed a significant change in the diaphragmatic motion and pulmonary function
      (FEV1, MVV). FEV1 and MVV showed significant differences when the PFM was
      contracted. Diaphragmatic motion showed a significant difference when the PFM was
      contracted. [Conclusion] Diaphragmatic motion and contraction of the PFM
      correlate with breathing. In addition, breathing is much more effective during
      contraction of the PFM. Therefore, PFM strengthening exercises should be included
      in respiratory rehabilitation programs. 

PMID- 26311936
TI  - Changes in corticospinal excitability with short-duration high-frequency
      electrical muscle stimulation: a transcranial magnetic stimulation study.
AB  - [Purpose] Afferent input caused by electrical stimulation of a peripheral nerve
      or a muscle modulates corticospinal excitability. However, a long duration of
      stimulation is required to induce these effects. The purpose of this study was to
      investigate the effect of short-duration high-frequency electrical muscle
      stimulation (EMS) on corticospinal excitability through the measurement of motor
      evoked potentials (MEP) in young healthy subjects. [Subjects] Eleven healthy
      right-handed subjects participated in this study. [Methods] EMS was applied to
      the abductor pollicis brevis (APB) muscle at 100 Hz with a pulse width of 100 MUs
      for 120 s. The intensity of stimulation was just below the motor threshold.
      Transcranial magnetic stimulation was applied over the motor cortex, and MEP were
      recorded from the APB before, and immediately, 10, and 20 min after EMS.
      [Results] In the APB muscle, the MEP amplitude significantly decreased after EMS,
      and this effect lasted for 20 min. [Conclusion] The excitability of the
      corticospinal tract decreased after short-duration high-frequency EMS, and the
      effect lasted for 20 min. These results suggest that even short duration EMS can
      change the excitability of the corticospinal tract. 

PMID- 26311938
TI  - Absolute reliability of shoulder joint horizontal adductor muscle strength
      measurements using a handheld dynamometer.
AB  - [Purpose] The aim of this study was to verify the absolute reliability of
      shoulder joint horizontal adductor muscle strength measurements using a handheld
      dynamometer (HHD). [Subjects and Methods] The subjects were 33 healthy college
      students. The measurements were made three times with the HHD fixed using a belt
      (BFHHD) or with the examiner's hand (conventional method; HFHHD). The absolute
      reliability of measurements was verified using Bland-Altman analysis, both in the
      all subjects group and a group of subjects showing measurements less than a fixed
      limit of 30 kgf. [Results] In the <30 kgf group, a systematic bias was not
      observed, and BFHHD values were greater than HFHHD values. BFHHD values in the
      all subjects group showed a systematic bias; the 3rd measurement value was less
      than the maximum value obtained during the 1st and 2nd measurements. [Conclusion]
      For obtaining an acceptable value during clinical measurements of horizontal
      adductor muscle strength, single measurements obtained using an HFHHD in the case
      of a <30 kgf group and the maximum value of two measurements obtained using a
      BFHHD are reliable. 

PMID- 26311937
TI  - The effects of respiratory muscle strengthening exercise using a sling on the
      amount of respiration.
AB  - [Purpose] The purpose of this study was to present aerobic exercise that can be
      performed together with respiratory muscle strength training and examine whether
      the vital capacity of individuals can be enhanced when respiratory muscle
      strength training is conducted together with aerobic exercise. [Subjects and
      Methods] The subjects were 10 male students and 8 female students. The sling
      exercise method was used to conduct three types of training to strengthen the
      muscles around the shoulder joints. A maximal respiratory quotient measurement
      device was used to measure the vital capacity of the subjects five times.
      [Results] There was a significant difference in each respiratory training time
      point compared with before the performance of respiratory training. [Conclusion]
      This study presented respiratory muscle strength training using a sling as a
      training method for respiratory training. 

PMID- 26311939
TI  - The effect of parity on pelvic floor muscle strength and quality of life in women
      with urinary incontinence: a cross sectional study.
AB  - [Purpose] The purpose of this study was to analyze the pelvic floor muscle (PFM)
      activity after vaginal birth, and the effect of parity on PFM strength and
      quality of life (QoL) in women with urinary incontinence. [Subjects and Methods]
      Patients (n=241) who gave birth vaginally and experienced urinary incontinence
      were divided into three groups: group 1 consisted of women having 1-3 children,
      group 2 consisted of women having 4-6 children, and group 3 consisted of women
      having more than 6 children. All patients underwent detailed examination of the
      PFM. The Turkish version of the self-administered Incontinence Quality of Life
      Instrument (I-QoL) questionnaire was used to evaluate the effects of stress
      urinary incontinence on participants' QoL. [Results] Comparison of PFM strengths
      showed a significant intergroup difference. Group 1 showed significantly higher
      PFM strength scores than those of groups 2 and 3. I-QoL scores related to stress
      incontinence showed a significant intergroup difference. As number of deliveries
      increased, quality of life decreased. Comparison of PFM strengths and I-QoL
      scores related to stress incontinence showed a significant intergroup difference.
      [Conclusion] Increasing the awareness of PFM training in women will reduce
      potential postpartum incontinence due to a weak PFM strength; and will increase
      quality of life. 

PMID- 26311940
TI  - Effectiveness of device-based therapy for conservative management of low back
      pain.
AB  - [Purpose] Device based therapy for low back pain (LBP) involves quantitative
      assessment of muscle strength, resistance and lumbar motion and tailoring the
      rehabilitation protocol based on this objective assessment. The purpose of this
      study was to determine the effectiveness of device based therapy for LBP.
      [Subjects and Methods] In this retrospective study, clinical data of 235 patients
      who underwent device-based physiotherapy for low back pain was reviewed. Pre and
      post-treatment outcome measures for pain (visual analogue scale or VAS score),
      disability (Oswestry disability index) and functional ability were compared to
      determine effectiveness of device-based physiotherapy at the end of 6 weeks of
      treatment. [Results] All outcome measures including VAS Score and mean Oswestry
      Disability Score showed significant improvement at the end of 6 weeks of device
      based physical therapy. Before treatment, 73% of patients had moderate to severe
      disability which reduced to 28% after treatment. [Conclusion] Device-based
      therapy is effective in relieving pain, improving function and reducing
      disability in patients with low back pain in the short term. Device-based therapy
      may help to objectively evaluate the function of the spine and paraspinal muscles
      and help the therapist tailor treatment accordingly. 

PMID- 26311941
TI  - Effect of the application of a metatarsal bar on pressure in the metatarsal bones
      of the foot.
AB  - [Purpose] The aim of this study was to determine the effect of application of a
      metatarsal bar on the pressure in the metatarsal bones of the foot using a foot
      analysis system (pressure on the forefoot, midfoot, and rearfoot). [Subjects and
      Methods] Forty female university students in their twenties were selected for
      this study, and an experiment was conducted with them as the subjects, before and
      after application of a metatarsal bar. The static foot regions were divided into
      the forefoot, midfoot, and rearfoot, and then the maximum, average, and low
      pressures exerted at each region were measured, along with the static foot
      pressure distribution ratio. 1) Static foot pressure: The tips of both feet were
      aligned to match the vertical and horizontal lines of the foot pressure measuring
      plate. The subjects were told to look toward the front and not to wear shoes. 2)
      Distribution ratio: The distribution ratio was measured in four regions (front,
      back, left, and right) using the same method as used for static foot pressure
      measurement. [Results] The results of this study showed that the maximum,
      average, and minimum static pressures in the forefoot were significantly
      decreased. The minimum static pressure in the midfoot was significantly
      increased, and the pressure in the other parts was significantly decreased. The
      maximum and average static pressures in the rearfoot were also significantly
      decreased. [Conclusion] As reduction of foot pressure with a metatarsal bar
      results in lowering of the arch and an increased contact surface, the foot
      pressure was dispersed. These results suggest that wearing shoes with a bar that
      can decrease the foot pressure is therapeutically helpful for patients with a
      diabetic foot lesion or rheumatoid arthritis. 

PMID- 26311942
TI  - Handgrip strength dominance is associated with difference in forearm muscle size.
AB  - [Purpose] It is unknown whether handgrip strength dominance is related to the
      size of the forearm flexor muscles. The purpose of the present study was to
      investigate the relationship between side-by-side differences in handgrip
      strength and forearm muscle thickness. [Subjects] Thirty-one young women (26
      right handed and 5 left handed) between the ages of 20 and 33 years volunteered
      to participate. [Methods] Two muscle thicknesses (forearm-ulna and forearm-radius
      muscle thicknesses) were measured using B-mode ultrasound at the anterior forearm
      on both sides of the body. Handgrip strength was also measured on both sides.
      [Results] The side-by-side difference in handgrip strength was 10.2% for the
      right-handed group, meaning the right hand was stronger. However, the left hand
      of the left-handed group was 7.8% stronger compared with their right hand. There
      was a significant positive correlation between side-by-side differences in
      handgrip strength and forearm-ulna muscle thickness (r = 0.765) and between
      handgrip strength and forearm-radius muscle thickness (r = 0.622). [Conclusion]
      Our results indicate that side-by-side differences in forearm muscle size may
      strongly contribute to handgrip strength dominance. 

PMID- 26311943
TI  - Effects of conventional neurological treatment and a virtual reality training
      program on eye-hand coordination in children with cerebral palsy.
AB  - [Purpose] The purpose of the study was to evaluate the effects of conventional
      neurological treatment and a virtual reality training program on eye-hand
      coordination in children with cerebral palsy. [Subjects] Sixteen children (9
      males, 7 females) with spastic diplegic cerebral palsy were recruited and
      randomly assigned to the conventional neurological physical therapy group (CG)
      and virtual reality training group (VRG). [Methods] Eight children in the control
      group performed 45 minutes of therapeutic exercise twice a week for eight weeks.
      In the experimental group, the other eight children performed 30 minutes of
      therapeutic exercise and 15 minutes of a training program using virtual reality
      twice a week during the experimental period. [Results] After eight weeks of the
      training program, there were significant differences in eye-hand coordination and
      visual motor speed in the comparison of the virtual reality training group with
      the conventional neurological physical therapy group. [Conclusion] We conclude
      that a well-designed training program using virtual reality can improve eye-hand
      coordination in children with cerebral palsy. 

PMID- 26311944
TI  - The effects of plantar flexor static stretching and dynamic stretching using an
      aero-step on foot pressure during gait in healthy adults: a preliminary study.
AB  - [Purpose] The aim of this study was to examine whether plantar flexor static
      stretching and dynamic stretching using an Aero-Step results in changes in foot
      pressure during gait in healthy adults. [Subjects] Eighteen normal adults were
      randomly allocated to either a dynamic stretching using an Aero-Step group
      (DSUAS) group (n = 8) or a static stretching (SS) group (n = 10). [Methods] The
      DSUAS and SS participants took part in an exercise program for 15 minutes.
      Outcome measures were foot plantar pressure, which was measured during the
      subject's gait stance phase; the asymmetric ratio of foot pressure for both feet;
      and the visual analogue scale (VAS) measured during the interventions. [Results]
      There were significant differences in the asymmetric ratio of foot pressure for
      both feet and VAS between the two groups after intervention. However, there were
      no significant differences in foot plantar pressure during the gait stance phase
      within both groups. [Conclusion] DSUSAS is an effective stretching method, as
      pain during it is lower than that with SS, which can minimize the asymmetric
      ratio of foot pressure for both feet during gait due to asymmetric postural
      alignment. 

PMID- 26311945
TI  - The effects of stretching exercise for upper trapezius on the asymmetric rate of
      bite force.
AB  - [Purpose] The purpose of this study was to observe the effects of stretching the
      upper trapezius muscle on the asymmetric rate of bite force. [Subjects] Forty
      seven female university students who had all their original teeth, had no
      disorders in the temporomandibular joints, and had never worn braces;
      participated in this study. [Methods] An occlusometer was used to measure biting
      forces. Subsequently, stretching exercises of the upper trapezius were performed.
      The subjects were divided into 3 groups at the start of the testing: the
      asymmetric rate of the first group was less than 10%; the asymmetric rate of the
      second group was between 10% and 20%; and the asymmetric rate of the third group
      was more than 20%. The stretching exercises were done on the dominant side of the
      upper trapezius. [Results] After the stretching exercises of the upper trapezius,
      the results showed that for the first group, whose asymmetric rate of biting
      force was less than 10%, there was a significant increase in asymmetric rate
      (from 5.1% to 10.3%). For the second group, whose asymmetric rate of biting force
      was measured to be between 10% and 20%, the asymmetric rate decreased from 14.7%
      to 14.3%, but the change was not statistically significant. For the third group,
      whose asymmetric rate of biting force was more than 20%, there was a significant
      decrease in asymmetric rate (from 27.8% to 12.6%). [Conclusion] We concluded that
      stretching exercises of the upper trapezius muscle had a direct effect on the
      asymmetric rate of biting force. 

PMID- 26311946
TI  - Test-retest reliability of expiratory abdominal compression with a handheld
      dynamometer in patients with prolonged mechanical ventilation.
AB  - [Purpose] The present study aimed to examine the test-retest reliability of
      expiratory abdominal compression with a handheld dynamometer in patients with
      prolonged mechanical ventilation. [Subjects and Methods] We recruited 18 patients
      with prolonged mechanical ventilation. All patients had impaired consciousness.
      The mode of the ventilator was synchronized intermittent mandatory ventilation.
      The abdomen above the navel was vertically compressed using a handheld
      dynamometer in synchronization with expiration. Expiratory abdominal compression
      was performed two times. We measured the tidal volume during expiratory abdominal
      compression. There was an interval of 5 minutes between the first and second
      measurements. Intraclass correlation coefficient (ICC) and Bland-Altman analysis
      were performed to examine the test-retest reliability of expiratory abdominal
      compression with a handheld dynamometer. [Results] The test-retest reliability of
      expiratory abdominal compression was excellent (ICC(1, 1): 0.987). Bland-Altman
      analysis showed that there was no fixed bias and no proportional bias.
      [Conclusion] The findings of this study suggest that expiratory abdominal
      compression with a handheld dynamometer is reliable and useful for patients with
      respiratory failure and prolonged mechanical ventilation. 

PMID- 26311947
TI  - Parameters affecting the tidal volume during expiratory abdominal compression in
      patients with prolonged tracheostomy mechanical ventilation.
AB  - [Purpose] The aim of this study was to clarify physical parameters affecting the
      tidal volume during expiratory abdominal compression in patients with prolonged
      tracheostomy mechanical ventilation. [Methods] Eighteen patients with prolonged
      mechanical ventilation were included in this study. Expiratory abdominal
      compression was performed on patients lying in a supine position. The abdomen
      above the navel was vertically compressed in synchronization with expiration and
      released with inspiration. We measured the tidal volume during expiratory
      abdominal compression. [Results] The mean tidal volume during expiratory
      abdominal compression was higher than that at rest (430.6 +/- 127.1 mL vs. 344.0
      +/- 94.3 mL). The tidal volume during expiratory abdominal compression was
      correlated with weight, days of ventilator support, dynamic compliance and
      abdominal expansion. Stepwise multiple regression analysis revealed that weight
      (beta = 0.499), dynamic compliance (beta = 0.387), and abdominal expansion (beta
      = 0.365) were factors contributing to the tidal volume during expiratory
      abdominal compression. [Conclusion] Expiratory abdominal compression increased
      the tidal volume in patients with prolonged tracheostomy mechanical ventilation.
      The tidal volume during expiratory abdominal compression was influenced by each
      of the pulmonary conditions and the physical characteristics. 

PMID- 26311948
TI  - Correlation between balance and gait according to pelvic displacement in stroke
      patients.
AB  - [Purpose] The purpose of this study was to investigate the correlations of
      balance and gait according to pelvic displacement in stroke patients. [Subjects]
      The subjects of this study were 58 stroke patients who had been admitted to a
      hospital. [Methods] A Global Postural System was used to measure pelvic
      displacement. To measure the balance ability, a Tetrax balance system was used to
      measure the weight distribution index and stability index. Gait ability was
      measured during the 10-Meter Walking Test and Figure-of-8 Walk Test. [Results]
      The results of this study showed that was significant positive correlation
      between the anterior superior iliac spine height difference in pelvic
      displacement and the weight distribution index and significant positive
      correlation between the posterior superior iliac spine height difference and the
      stability index in the normal position with the eyes closed. Statistically
      significant positive correlation also was found between the anterior superior
      iliac spine height difference and the straight and curved gait ability.
      [Conclusion] The increased pelvic displacement in stroke patients results in a
      decrease in balance ability and gait speed. This suggests that control of pelvic
      displacement is necessary before functional training for patients with stroke. 

PMID- 26311949
TI  - Effect of a virtual reality exercise program accompanied by cognitive tasks on
      the balance and gait of stroke patients.
AB  - [Purpose] This study aimed to assess the effect of a virtual reality exercise
      program accompanied by cognitive tasks on the balance and gait of stroke
      patients. [Subjects] Twenty stroke patients were randomly assigned to two groups
      10 to an experimental group that performed a virtual reality exercise program
      accompanied by cognitive tasks and 10 to a control group. The control group
      performed a proprioceptive neuromuscular facilitation exercise program. Balance
      was measured with the Berg Balance Scale. Gait was assessed using the Timed Up
      and Go Test. The paired t-test was used to compare groups before and after the
      experiment. The independent t-test was conducted to assess differences in the
      degree of change between the two groups before and after the experiment.
      [Results] Within-group comparison in the experimental group showed significant
      differences in the Berg Balance Scale and Timed Up and Go Test. In a comparison
      between groups, the differences in the Berg Balance Scale and Timed Up and Go
      Test in the experimental group appeared significant compared with the control
      group. [Conclusion] The results of the experiment indicate that a virtual reality
      exercise program accompanied by cognitive tasks has a positive effect on the
      balance and gait of stroke patients. 

PMID- 26311950
TI  - Measuring seated hip extensor strength using a handheld dynamometer: an
      examination of the reliability and validity of the protocol.
AB  - [Purpose] The purpose of this study was to examine the reliability and validity
      of measurements of hip extensor muscle strength using a handheld dynamometer
      (HHD) with subjects in a sitting position. In doing so, we also aimed to
      establish a modified method of measurement for patients with flexion contractures
      in the trunk and lower extremities. [Subjects and Methods] In 20 healthy males,
      hip extensor muscle strength was measured using a handheld dynamometer in
      sitting, prone, and standing positions by contracting the hip extensor muscle
      isometrically with the knee flexed at 90 degrees. For each position, we
      investigated the relative and absolute reliability and validity of the
      measurements, and compared muscle strength between the different positions.
      [Results] The reliability and validity of measurements were highest in the
      sitting position and higher in both the sitting and standing positions as
      compared with those in the prone position. [Conclusion] Our findings suggest that
      measurements taken in a sitting position are accurate in assessing hip extensor
      muscle strength and would be applicable to patients with flexion contractures in
      the trunk and lower extremities. 

PMID- 26311951
TI  - Perceived body discomfort and trunk muscle activity in three prolonged sitting
      postures.
AB  - [Purpose] This study aimed to investigate the perceived discomfort and trunk
      muscle activity in three different 1-hour sitting postures. [Subjects] A repeated
      measures design study was conducted on 10 healthy subjects. [Methods] Each
      subject sat for an hour in three sitting postures (i.e., upright, slumped, and
      forward leaning sitting postures). Subjects rated perceived body discomfort using
      Borg's CR-10 scale at the beginning and after 1 hour sitting. The
      electromyographic activity of the trunk muscle activity was recorded during the 1
      hour period of sitting. [Results] The forward leaning sitting posture led to
      higher Borg scores in the low back than those in the upright (p = 0.002) and
      slumped sitting postures (p < 0.001). The forward leaning posture was
      significantly associated with increased iliocostalis lumborum pars thoracis (ICL)
      and superficial lumbar multifidus (MF) muscle activity compared with the upright
      and slumped sitting postures. The upright sitting posture was significantly
      associated with increased internal oblique (IO)/transversus abdominis (TrA) and
      ICL muscle activity compared with the slumped sitting posture. [Conclusion] The
      sitting posture with the highest low back discomfort after prolonged sitting was
      the forward leaning posture. Sitting in an upright posture is recommended because
      it increases IO/TrA muscle activation and induces only relatively moderate ICL
      and MF muscle activation. 

PMID- 26311952
TI  - Exercise is associated with metabolism regulation and complications in Korean
      patients with type 2 diabetes.
AB  - [Purpose] The aim of the present study was to investigate the current evidence
      for the effect of exercise on glycemic control, the lipid profile, body
      composition, vascular health, and complications in Korean patients with type 2
      diabetes. [Subjects and Methods] The subjects were 1,263 patients receiving
      outpatient care at 13 general hospitals located in Seoul and Gyeonggido who were
      subjected to examinations in the areas of blood glucose management, complications
      management, and diabetes education between March 19 and May 29, 2013. The
      relations between exercise and various regulatory factors including patient's
      general and clinical characteristics, metabolic regulation, achievement of goals
      for metabolic regulation, and complication incidence in patients with type 2
      diabetes were investigated. [Results] Exercise management was associated with a
      decrease in systolic blood pressure, fasting glucose, postprandial glucose,
      hemoglobin A1c, total cholesterol, triglyceride, and low-density lipoprotein
      Regarding achievement of goals for metabolic regulation, significant odds ratios
      were observed for the effect of exercise treatment on blood pressure, fasting
      glucose, postprandial glucose, hemoglobin A1c, triglyceride, HDL in men, and BMI
      in patients with type 2 diabetes. Moreover, exercise management was associated
      with decreased occurrence of cerebrovasculopathy. [Conclusion] In conclusion,
      exercise induced metabolic regulation of glycemic control, the lipid profile, and
      body composition, as well as vascular health and complications, in Korean
      patients with type 2 diabetes. 

PMID- 26311953
TI  - Effect of shoulder girdle strengthening on trunk alignment in patients with
      stroke.
AB  - [Purpose] This study investigated the effect of shoulder girdle strengthening,
      particularly the scapular muscles, on poststroke trunk alignment. [Subjects and
      Methods] The study involved 30 patients with residual hemiparesis following
      cerebrovascular stroke. Patient assessment included measuring shoulder muscle
      peak torque, scapular muscles peak force, spinal lateral deviation angle, and
      motor functional performance. Patients were randomly allocated either to the
      control group or the study group and received an 18-session strengthening program
      including active resisted exercises for shoulder abductors and external rotators
      in addition to trunk control exercises. The study group received additional
      strengthening exercises for the scapular muscles. [Results] The two groups showed
      significant improvement in strength of all shoulder and scapular muscles, with
      higher improvement in the study group. Similarly, the lateral spinal deviation
      angles significantly improved in both groups, with significantly higher
      improvement in the study group. Transfer activity, sitting balance, upper limb
      functions, and hand movements significantly improved in the two groups, with
      higher improvement in the latter two functions in the study group. [Conclusion]
      Strengthening of shoulder girdle muscles, particularly scapular muscles, can
      significantly contribute to improving the postural alignment of the trunk in
      patients with poststroke hemiparesis. 

PMID- 26311954
TI  - Relationship between trunk stability during voluntary limb and trunk movements
      and clinical measurements of patients with chronic stroke.
AB  - [Purpose] The purposes of this study were to investigate differences between
      patients with chronic stroke and age matched healthy controls in trunk stability,
      by assessing the kinematics of the center of mass and moving body segments during
      voluntary limb and trunk movement, and the relationship between trunk stability
      and clinical measurements. [Subjects and Methods] Fifteen stroke patients and 15
      age- and gender-matched healthy subjects participated. Each subject performed
      flexion of the hip and shoulder of the non-paretic or matched side as fast as
      possible, as well as trunk flexion and extension at a self-selected speed. A
      Qualisys motion system was employed to track the kinematics of the trunk and
      limbs. [Results] Patients presented larger mediolateral displacement of the
      center of mass during all limb and trunk movements, and larger velocity of center
      of mass during hip flexion movement. Healthy subjects showed greater movement
      velocity during shoulder flexion, trunk flexion and extension. Patients' clinical
      measurements only correlated with movement characteristics during voluntary trunk
      motions. [Conclusion] Trunk stability in patients with chronic stroke was
      compromised during voluntary trunk as well as non-paretic limb movements, and the
      voluntary trunk movements reflected the trunk deficits measured using clinical
      measurements. Rehabilitation of patients with chronic stroke should include
      programs to improve trunk stability. 

PMID- 26311955
TI  - Associations between the settings of exercise habits and health-related outcomes
      in community-dwelling older adults.
AB  - [Purpose] The purpose of this study was to examine the associations between the
      settings of exercise habits and health-related outcomes in community-dwelling
      older adults. [Subjects] A total of 304 Japanese community-dwelling older adults
      (70.3 +/- 4.1 years; 113 males and 191 females) participated in this study.
      [Methods] Demographic characteristics, medical conditions, exercise habits, and
      health-related outcomes were assessed by face-to-face interviews and self
      reported questionnaires. Older adults who had exercise habits were classified
      into two groups: individual- and group-based exercise habits groups, and the
      health-related outcomes were compared between groups. [Results] The scores for
      the Geriatric Depression Scale, exercise self-efficacy, and dietary variety of
      older adults who had group-based exercise habits were better than those of older
      adults who had individual-based exercise habits. In addition, the exercise
      settings (individual- and group-based) were significantly associated with scores
      for the Geriatric Depression Scale (odds ratio = 0.76) and exercise self-efficacy
      (odds ratio = 1.26), even after adjusting for age and gender. [Conclusion] These
      results implied that habitual exercise in group settings may have an effective
      role in promoting exercise self-efficacy and mental health. 

PMID- 26311956
TI  - Ulnar nerve entrapment neuropathy at the elbow: relationship between the
      electrophysiological findings and neuropathic pain.
AB  - [Purpose] Ulnar nerve neuropathies are the second most commonly seen entrapment
      neuropathies of the upper extremities after carpal tunnel syndrome. In this
      study, we aimed to evaluate pain among ulnar neuropathy patients by the Leeds
      assessment of neuropathic symptoms and signs pain scale and determine if it
      correlated with the severity of electrophysiologicalfindings. [Subjects and
      Methods] We studied 34 patients with clinical and electrophysiological ulnar
      nerve neuropathies at the elbow. After diagnosis of ulnar neuropathy at the
      elbow, all patients underwent the Turkish version of the Leeds assessment of
      neuropathic symptoms and signs pain scale. [Results] The ulnar entrapment
      neuropathy at the elbow was classified as class-2, class-3, class-4, and class-5
      (Padua Distal Ulnar Neuropathy classification) for 15, 14, 4, and 1 patient,
      respectively. No patient included in class-1 was detected. According to Leeds
      assessment of neuropathic symptoms and signs pain scale, 24 patients scored under
      12 points. The number of patients who achieved more than 12 points was 10. Groups
      were compared by using the chi(2) test, and no difference was detected. There was
      no correlation between the Leeds assessment of neuropathic symptoms and signs
      pain scale and electromyographic findings. [Conclusion] We found that the
      severity of electrophysiologic findings of ulnar nerve entrapment at the elbow
      did not differ between neuropathic and non-neuropathic groups as assessed by the
      Leeds assessment of neuropathic symptoms and signs pain scale. 

PMID- 26311957
TI  - Identification of the affected lower limb and unaffected side motor functions as
      determinants of activities of daily living performance in stroke patients using
      partial correlation analysis.
AB  - [Purpose] This study aimed to clarify the independent impact of the affected
      upper and lower limb, trunk, and unaffected side motor functions on activities of
      daily living in stroke patients using partial correlation analysis. [Subjects and
      Methods] This retrospective study included 77 stroke patients. Motor functions
      were assessed using the Stroke Impairment Assessment Set, and the activities of
      daily living performance was assessed using the Barthel index or Functional
      Independence Measure. Further, simple and partial correlation analyses were
      conducted between each motor function and activities of daily living parameter.
      [Results] Simple correlation analysis identified significant positive
      correlations for each pair. In contrast, partial correlation analysis only
      identified significant positive correlations between the affected lower limb or
      unaffected side functions and the Barthel index or Functional Independence
      Measure. This discrepancy between the two tests was explained by the significant
      interaction between the affected upper and lower limb functions and between the
      trunk and unaffected side functions. [Conclusion] The present study identified
      the affected lower limb and unaffected side motor functions as the major
      determinants of activities of daily living performance in stroke patients. These
      findings suggest that rehabilitation programs can be improved by targeting these
      areas. 

PMID- 26311958
TI  - Effect of a 12-week aerobic training program on perceptual and affective
      responses in obese women.
AB  - [Purpose] The aim of this study was to observe the effect of self-selected
      intensity or imposed intensity during aerobic training on perceptual and
      affective responses in obese women. [Subjects] The study included 26 obese women
      aged 30-60 years. [Methods] The subjects were randomly divided into two groups,
      with 13 subjects in each group: self-selected intensity and imposed intensity
      (10% above ventilatory threshold) groups. All subjects completed an intervention
      program that lasted 12 weeks, with three exercise sessions a week. The rating of
      perceived exertion and affective responses (Feeling Scale and Felt Arousal Scale)
      were monitored in the first, sixth, and twelfth weeks. [Results] Significant
      differences were observed between groups in heart rate and rating of perceived
      exertion. The affective responses during exercise were more negative in the
      imposed intensity group. [Conclusion] Use of a self-selected exercise intensity
      can promote smaller negative affective responses during exercise and provide a
      sufficient stimulus for improvement in cardiorespiratory fitness. 

PMID- 26311959
TI  - Does aerobic exercise affect the hypothalamic-pituitary-adrenal hormonal response
      in patients with fibromyalgia syndrome?
AB  - [Purpose] The hypothalamic-pituitary-adrenal (HPA) axis in the etiopathogenesis
      of fibromyalgia is not clear. This study aimed to analyze the effects of a 6-week
      aerobic exercise program on the HPA axis in patients with fibromyalgia and to
      investigate the effects of this program on the disease symptoms, patients'
      fitness, disability, and quality of life. [Subjects and Methods] Fifty
      fibromyalgia patients were randomized to Group 1 (stretching and flexibility
      exercises at home for 6 weeks) and Group 2 (aerobic exercise three times a week
      and the same at-home exercises as Group 1 for 6 weeks). Serum levels of cortisol,
      adrenocorticotropic hormone, insulin-like growth factor-1, and growth hormone
      were analyzed at baseline and at the end of, and 1 hr after an exercise stress
      test. [Results] Group 2 showed better improvement in morning stiffness duration
      and pain. Growth hormone levels significantly increased after intervention and
      cortisol levels significantly decreased at time-time interaction in both groups.
      No significant differences in adrenocorticotropic hormone and insulin-like growth
      factor-1 were found. [Conclusion] The results of this study seem to support the
      hypothesis that there is a dysregulation of the HPA axis in patients with FM, and
      that a six-week exercise program can influence symptoms and affect the HPA axis
      hormones. 

PMID- 26311960
TI  - Is there a difference in the electromyographic activity of the pelvic floor
      muscles across the phases of the menstrual cycle?
AB  - [Purpose] To evaluate the electrical activity of the pelvic floor muscle in women
      during the follicular, ovulatory, and luteal phases of the menstrual cycle and
      its correlation with estradiol and total testosterone levels. [Subjects and
      Methods] This cross-sectional study involved 30 women with ovulatory menstrual
      cycles. Total testosterone and estradiol levels were measured and the muscle tone
      and maximum voluntary contraction of the pelvic floor muscles were evaluated
      using surface electromyography. [Results] Muscle tone was significantly lower
      during the follicular (21.1+/-3.3 MUV) and ovulatory (27.1+/-5.9 MUV) phases than
      the luteal phase (30.4+/-4.1 MUV). The maximum voluntary contraction was not
      different across phases. The estradiol level on the 7th day of the menstrual
      cycle showed a strong positive correlation with muscle tone and maximum voluntary
      contraction, and the testosterone level was positively correlated with muscle
      tone on the 21st day. [Conclusion] Women have better muscle tone during the
      luteal phase. The muscle tone and maximum voluntary contraction were strongly
      correlated with the estradiol level on the 7th day, and the muscle tone was
      correlated with the testosterone level on the 21st day of the menstrual cycle.
      These findings suggest that hormonal fluctuations during the menstrual cycle
      alter pelvic floor muscle activity. 

PMID- 26311961
TI  - Prevalence of low back pain and associated factors among farmers during the rice
      transplanting process.
AB  - [Purpose] The aim of this study was to investigate the prevalence of low back
      pain and associated factors in Thai rice farmers during the rice transplanting
      process. [Subjects and Methods] Three hundred and forty-four farmers, aged 20-59
      years old, were asked to answer a questionnaire modified from the Standard Nordic
      Questionnaire (Thai version). The questionnaire sought demographic, back-related,
      and psychosocial data. [Results] The results showed that the prevalence of low
      back pain was 83.1%. Farmers younger than 45 years old who worked in the field
      fewer than six days were more likely to experience low back pain than those who
      worked for at least six days. Farmers with high stress levels were more likely to
      have low back pain. [Conclusion] In the rice transplanting process, the low back
      pain experienced by the farmers was associated with the weekly work duration and
      stress. 

PMID- 26311962
TI  - Relationship between paraspinal muscle cross-sectional area and relative
      proprioceptive weighting ratio of older persons with lumbar spondylosis.
AB  - [Purpose] The purpose of this study was to examine the relationship between the
      paraspinal muscle cross-sectional area and the relative proprioceptive weighting
      ratio during local vibratory stimulation of older persons with lumbar spondylosis
      in an upright position. [Subjects] In all, 74 older persons hospitalized for
      lumbar spondylosis were included. [Methods] We measured the relative
      proprioceptive weighting ratio of postural sway using a Wii board while vibratory
      stimulations of 30, 60, or 240 Hz were applied to the subjects' paraspinal or
      gastrocnemius muscles. Back strength, abdominal muscle strength, and erector
      spinae muscle (L1/L2, L4/L5) and lumbar multifidus (L1/L2, L4/L5) cross-sectional
      areas were evaluated. [Results] The erector spinae muscle (L1/L2) cross-sectional
      area was associated with the relative proprioceptive weighting ratio during 60Hz
      stimulation. [Conclusion] These findings show that the relative proprioceptive
      weighting ratio compared to the erector spinae muscle (L1/L2) cross-sectional
      area under 60Hz proprioceptive stimulation might be a good indicator of trunk
      proprioceptive sensitivity. 

PMID- 26311963
TI  - Comparison of changes in tidal volume associated with expiratory rib cage
      compression and expiratory abdominal compression in patients on prolonged
      mechanical ventilation.
AB  - [Purpose] This study was designed to compare and clarify the relationship between
      expiratory rib cage compression and expiratory abdominal compression in patients
      on prolonged mechanical ventilation, with a focus on tidal volume. [Subjects and
      Methods] The subjects were 18 patients on prolonged mechanical ventilation, who
      had undergone tracheostomy. Each patient received expiratory rib cage compression
      and expiratory abdominal compression; the order of implementation was randomized.
      Subjects were positioned in a 30 degrees  lateral recumbent position, and a 2-kgf
      compression was applied. For expiratory rib cage compression, the rib cage was
      compressed unilaterally; for expiratory abdominal compression, the area directly
      above the navel was compressed. Tidal volume values were the actual measured
      values divided by body weight. [Results] Tidal volume values were as follows: at
      rest, 7.2 +/- 1.7 mL/kg; during expiratory rib cage compression, 8.3 +/- 2.1
      mL/kg; during expiratory abdominal compression, 9.1 +/- 2.2 mL/kg. There was a
      significant difference between the tidal volume during expiratory abdominal
      compression and that at rest. The tidal volume in expiratory rib cage compression
      was strongly correlated with that in expiratory abdominal compression.
      [Conclusion] These results indicate that expiratory abdominal compression may be
      an effective alternative to the manual breathing assist procedure. 

PMID- 26311964
TI  - The effects of backpack loads and spinal stabilization exercises on the dynamic
      foot pressure of elementary school children with idiopathic scoliosis.
AB  - [Purpose] The purpose of this study was to measure and observe the changes in
      dynamic plantar pressures when school children carried specific bag loads, and to
      determine whether improved physical balance after an eight-week spinal
      stabilization exercise program can influences plantar pressures. [Subjects] The
      subjects were 10 school students with Cobb angles of 10 degrees  or greater.
      [Methods] Gait View Pro 1.0 (Alfoots, Korea) was were based on to measure the
      pressure of the participants' feet. Spinal stabilization exercises used TOGU
      Multi-roll Functional (TOGU, Germany) training. Dynamic plantar pressures were
      measured with bag loads of 0% no bag and 15% of subjects' body weight. The
      independent t test was performed to analyze changes in plantar pressures.
      [Results] The plantar pressure measurements of bag load of 0% of subjects' body
      weight before and after the spinal stabilization exercise program were not
      significantly different, but those of two foot areas with a 15% load were
      statistically significant (mt5, 67.32+/-24.25 and 51.77+/-25.52 kPa; lat heel,
      126.00+/-20.46 and 102.08+/-23.87 kPa). [Conclusion] After performance of the
      spinal stabilization exercises subjects' overall plantar pressures were reduced,
      which may suggest that physical balance improved. 

PMID- 26311966
TI  - Effects of horseback riding exercise therapy on hormone levels in elderly
      persons.
AB  - [Purpose] The purpose of this study was to investigate the effect of riding
      exercise on hormone levels in normal elderly people who were taught horseback
      riding for 8 weeks. [Subjects] Subjects were classified into an exercise group
      (n=10) and control group (n=10). [Methods] The two groups, horseback riding
      exercise group of 10 and control group of 10, were each tested for 15 minutes, 3
      times, over 8 weeks. Post-exercise tests were implemented in both groups in the
      same way as pre-study tests. [Results] The horseback riding group showed a
      significant difference in the pre- and post-exercise serotonin and cortisol
      levels. Additionally, serotonin and cortisol levels showed significant
      differences between the two groups. [Conclusion] Serotonin and cortisol levels
      significantly increased in the experimental group, suggesting that horseback
      riding exercise is effective for improving the levels of these hormones. 

PMID- 26311965
TI  - Physical activity and lifestyle effects on bone mineral density among young
      adults: sociodemographic and biochemical analysis.
AB  - [Purpose] The purpose of this study was to assess the possible role of physical
      activities, calcium consumption and lifestyle factors in both bone mineral
      density and bone metabolism indices in 350 young adult volunteers. [Subjects and
      Methods] All volunteers were recruited for the assessment of lifestyle behaviors
      and physical activity traits using validated questioners, and bone mineral
      density (BMD), serum osteocalcin (s-OC), bone-specific alkaline phosphatase
      (BAP), and calcium were estimated using dual-energy X-ray absorptiometry
      analysis, and immunoassay techniques. [Results] Male participants showed a
      significant increase in BMD along with an increase in bone metabolism markers
      compared with females in all groups. However, younger subjects showed a
      significant increase in BMD, OC, BAP, and calcium compared with older subjects.
      Osteoporosis was more common in older subjects linked with abnormal body mass
      index and waist circumference. Bone metabolism markers correlated positively with
      BMD, physically activity and negatively with osteoporosis in all stages. Also,
      moderate to higher calcium and milk intake correlated positively with higher BMD.
      However, low calcium and milk intake along with higher caffeine, and carbonated
      beverage consumption, and heavy cigarette smoking showed a negative effect on the
      status of bone mineral density. Stepwise regression analysis showed that life
      style factors including physical activity and demographic parameters explained
      around 58-69.8% of the bone mineral density variation in young adults especially
      females. [Conclusion] body mass index, physical activity, low calcium
      consumption, and abnormal lifestyle have role in bone mineral density and
      prognosis of osteoporosis in young adults. 

PMID- 26311967
TI  - Effects of flexi-bar and non-flexi-bar exercises on trunk muscles activity in
      different postures in healthy adults.
AB  - [Purpose] The purpose of this study was to assess the effects of flexi-bar
      exercises and non-flexi-bar exercises on trunk muscle activity in different
      postures in healthy adults. [Subjects] Twenty healthy right-hand dominant adults
      (10 males and 10 females) were selected for this study. None of the participants
      had experienced any orthopedic problems in the spine or in the upper and lower
      extremities in the previous six months. [Methods] The subjects were instructed to
      adopt three exercise postures: posture 1, quadruped; posture 2, side-bridge; and
      posture 3, standing. Surface electromyography of selected trunk muscles was
      normalized to maximum voluntary isometric contraction. [Results] The external
      oblique, internal oblique, and erector spinae muscle activity showed significant
      differences between flexi-bar exercises and non-flexi-bar exercises. [Conclusion]
      The results of this study suggest that flexi-bar exercises are useful in the
      activation of trunk muscles. 

PMID- 26311968
TI  - Motor imagery training improves upper extremity performance in stroke patients.
AB  - [Purpose] The purpose of this study was to investigate whether motor imagery
      training has a positive influence on upper extremity performance in stroke
      patients. [Subjects and Methods] Twenty-four patients were randomly assigned to
      one of the following two groups: motor imagery (n = 12) or control (n = 12). Over
      the course of 4 weeks, the motor imagery group participated in 30 minutes of
      motor imagery training on each of the 18 tasks (9 hours total) related to their
      daily living activities. After the 4-week intervention period, the Fugl-Meyer
      Assessment-Upper Extremity outcomes and Wolf Motor Function Test outcomes were
      compared. [Results] The post-test score of the motor imagery group on the Fugl
      Meyer Assessment-Upper Extremity outcomes was significantly higher than that of
      the control group. In particular, the shoulder and wrist sub-items demonstrated
      improvement in the motor imagery group. [Conclusion] Motor imagery training has a
      positive influence on upper extremity performance by improving functional
      mobility during stroke rehabilitation. These results suggest that motor imagery
      training is feasible and beneficial for improving upper extremity function in
      stroke patients. 

PMID- 26311969
TI  - Benefits of short-term structured exercise in non-overweight women with
      polycystic ovary syndrome: a prospective randomized controlled study.
AB  - [Purpose] The short-term effects of structured exercise on the anthropometric,
      cardiovascular, and metabolic parameters of non-overweight women diagnosed with
      polycystic ovary syndrome were evaluated. [Subjects and Methods] Thirty women
      with a diagnosis of polycystic ovary syndrome were prospectively randomized to
      either a control group (n=16) or a training group (n=14) for a period of 8 weeks.
      Anthropometric, cardiovascular, and metabolic parameters and hormone levels were
      measured and compared before and after the intervention. [Results] Waist and hip
      measurements (anthropometric parameters); diastolic blood pressure; respiratory
      rate (cardiovascular parameters); levels of low-density lipoprotein cholesterol,
      total cholesterol, fasting glucose, and fasting insulin; and the homeostasis
      model assessment of insulin resistance index (metabolic parameters) were
      significantly lower in the training group after 8 weeks of exercise compared to
      the baseline values. After exercise, the training group had significantly higher
      oxygen consumption and high-density lipoprotein levels and significantly shorter
      menstrual cycle intervals. The corresponding values for controls did not
      significantly differ between the start and end of the 8-week experiment.
      [Conclusion] Short-term regular exercise programs can lead to improvements in
      anthropometric, cardiovascular, and metabolic parameters of non-overweight women
      with polycystic ovary syndrome. 

PMID- 26311970
TI  - Comparison of center-of-pressure displacement during sit-to-stand according to
      chair height in children with cerebral palsy.
AB  - [Purpose] In patients with cerebral palsy (CP), performance of the sit-to-stand
      (STS) task is influenced by an asymmetrical motor pattern. The purpose of this
      study was to analyze the effects of an elevated chair on STS performance in
      patients with CP. [Subjects and Methods] Nine CP patients performed STS from a
      height-adjustable instrumented chair at their natural speed, with the ankle at a
      90 degrees  angle to the floor. The center-of-pressure (COP) displacement was
      recorded under the feet. Each foot position was tested at two chair heights
      corresponding to 100% and 120% of the leg length. The extent and speed of COP
      were calculated. [Results] The anteroposterior speed and extent of COP were
      greater with the standard chair than with the elevated chair. The other
      parameters such as mediolateral speed, extent, and vertical speed of the COP were
      not different between the two chairs. [Conclusion] These findings suggest that
      the sway with STS performed from the elevated chair was lesser than that with STS
      performed from the standard chair. This information will be relevant to
      clinicians involved in the rehabilitation of CP patients and will help identify
      factors that influence STS performance. 

PMID- 26311971
TI  - Effects of ankle strengthening exercises combined with motor imagery training on
      the timed up and go test score and weight bearing ratio in stroke patients.
AB  - [Purpose] The purpose of the present study was to compare the effects of ankle
      strengthening exercises combined with motor imagery training and those of ankle
      strengthening exercises alone in stroke patients. [Subjects and Methods] Thirty
      stroke patients were randomly assigned to one of the following two groups:
      experimental group (15 patients) and control group (15 patients). The
      experimental group underwent motor imagery training for 15 minutes and ankle
      joint strengthening exercises for 15 minutes, while the control group underwent
      only ankle joint strengthening exercises for 30 minutes. Each session and
      training program was implemented four times a week for 4 weeks. The timed up and
      go (TUG) test score, affected-side weight bearing ratio, and affected-side
      front/rear weight bearing ratio were assessed. [Results] Both groups demonstrated
      improvement on the TUG test, and in the affected-side weight bearing ratios,
      affected-side front/rear weight bearing ratios, and balance errors. The
      experimental group demonstrated greater improvement than the control group in all
      variables. [Conclusion] Motor imagery training is an effective treatment method
      for improving static balance ability in stroke patients. 

PMID- 26311972
TI  - Effects of diaphragm respiration exercise on pulmonary function of male smokers
      in their twenties.
AB  - [Purpose] We investigated how diaphragm respiration exercises can affect
      pulmonary function in long-term male smokers in their twenties. [Subjects and
      Methods] Twenty-eight healthy males between 20 and 29 years of age were randomly
      divided into an experimental and a control group (14 members each). The
      experiment was conducted during 30 min sessions, 3 times a week for 4 weeks. The
      experimental group performed diaphragm respiration exercises and the control
      group performed exercises using MOTOmed. Pulmonary function (tidal volume,
      breathing capacity, inspiratory reserve volume, inspiratory capacity, and
      expiratory reserve volume) was evaluated and analyzed before and after the
      experiment. [Results] Our results revealed significant increases in tidal volume,
      inspiratory reserve volume, inspiratory capacity, and breathing capacity in the
      experimental group. These increases were greater in the experimental group than
      in the control group. [Conclusion] In our study, the experimental group which
      performed diaphragm respiration exercises showed a greater improvement in
      pulmonary function compared with the control group. It is hypothesized that
      greater improvement in pulmonary function is expected if diaphragm respiration
      exercises are implemented taking into account the age of the smokers. 

PMID- 26311973
TI  - Effects of static interventions on disuse atrophy of the rat soleus muscle at
      different sites along its longitudinal axis.
AB  - [Purpose] The purpose of our study was to verify the inhibitory effects of static
      intervention (heat load and muscle stretching) on disuse-related adaptation
      changes in the soleus muscle and to compare these effects across different sites
      along its longitudinal axis. [Subjects] Forty 8-week-old male Wistar rats.
      [Methods] The effects of heat load and/or muscle stretching in the rat soleus
      during hindlimb suspension were evaluated by measuring the cross-sectional area
      of the muscle fibers, succinate dehydrogenase activity, and number of capillaries
      in the proximal, middle, and distal regions. [Results] With no intervention the
      proximal region showed the highest reduction in the cross-sectional area, whereas
      the distal region showed the highest reduction in succinate dehydrogenase
      activity and the number of capillaries due to hindlimb suspension. These
      differences between the proximal and distal regions decreased with both
      interventions, and the effects were most pronounced with a combination of heat
      load and muscle stretching. [Conclusion] Differences in the muscle structure
      between the proximal and distal regions increased due to hindlimb suspension, and
      this heterogeneity associated with muscle disuse was inhibited by static
      intervention including heat load and muscle stretching. Furthermore, the
      combination of heat load and muscle stretching most reduced the heterogeneity. 

PMID- 26311974
TI  - Muscle activity, time to fatigue, and maximum task duration at different levels
      of production standard time.
AB  - [Purpose] This study investigated the variations in muscle fatigue, time to
      fatigue, and maximum task duration at different levels of production standard
      time. [Methods] Twenty subjects performed repetitive tasks at three different
      levels of production standard time corresponding to "normal", "hard" and "very
      hard". Surface electromyography was used to measure the muscle activity.
      [Results] The results showed that muscle activity was significantly affected by
      the production standard time level. Muscle activity increased twice in percentage
      as the production standard time shifted from hard to very hard (6.9% vs. 12.9%).
      The muscle activity increased over time, indicating muscle fatigue. The muscle
      fatigue rate increased for the harder production standard time (Hard: 0.105; Very
      hard: 0.115), which indicated the associated higher risk of work-related
      musculoskeletal disorders. Muscle fatigue was also found to occur earlier for
      hard and very hard production standard times. [Conclusion] It is recommended that
      the maximum task duration should not exceed 5.6, 2.9, and 2.2 hours for normal,
      hard, and very hard production standard times, respectively, in order to maintain
      work performance and minimize the risk of work-related musculoskeletal disorders.

PMID- 26311975
TI  - Effects of a 12-hour neuromuscular electrical stimulation treatment program on
      the recovery of upper extremity function in sub-acute stroke patients: a
      randomized controlled pilot trial.
AB  - [Purpose] This study investigated the effects of a 12-hour neuromuscular
      electrical stimulation program in the evening hours on upper extremity function
      in sub-acute stroke patients. [Subjects and Methods] Forty-five subjects were
      randomized to one of three groups: 12-hour neuromuscular electrical stimulation
      group (n=15), which received 12 hours of neuromuscular electrical stimulation and
      conventional rehabilitation for the affected upper extremity; neuromuscular
      electrical stimulation group (n=15), which received 30 min of neuromuscular
      electrical stimulation and conventional rehabilitation; and control group (n=15),
      which received conventional rehabilitation only. The Fugl-Meyer assessment,
      Action Research Arm Test, and modified Ashworth scale were used to evaluate the
      effects before and after intervention, and 4 weeks later. [Results] The
      improvement in the distal (wrist-hand) components of the Fugl-Meyer assessment
      and Action Research Arm Test in the 12-hour neuromuscular electrical stimulation
      group was more significant than that in the neuromuscular electrical stimulation
      group. No significant difference was found between the two groups in the proximal
      component (shoulder-elbow) of the Fugl-Meyer assessment. [Conclusion] The 12-hour
      neuromuscular electrical stimulation group achieved better improvement in upper
      extremity motor function, especially in the wrist-hand function. This alternative
      therapeutic approach is easily applicable and can be used in stroke patients
      during rest or sleep. 

PMID- 26311976
TI  - Reliability and validity of an ultrasound-based imaging method for measuring
      interspinous process distance in the lumbar spine using two different index
      points.
AB  - [Purpose] This study assessed the reliability and validity of an ultrasound-based
      imaging method for measuring the interspinous process distance in the lumbar
      spine using two different index points. [Subjects and Methods] Ten healthy males
      were recruited. Five physical therapy students participated in this study as
      examiners. The L2-L3 interspinous distance was measured from the caudal end of
      the L2 spinous process to the cranial end of the L3 spinous process (E-E
      measurement) and from the top of the L2 spinous process to the top of the L3
      spinous process (T-T measurement). Intraclass correlation coefficients were
      calculated to estimate the relative reliability. Validity was assessed using a
      model resembling the living human body. [Results] The reliability study showed no
      difference in intra-rater reliability between the two measurements. However, the
      E-E measurement showed higher inter-rater reliability than the T-T measurement
      (Intraclass correlation coefficients: 0.914 vs. 0.725). Moreover, the E-E
      measurement method had good validity (Intraclass correlation coefficients: 0.999
      and 95% confidence interval for minimal detectable change: 0.29 mm). [Conclusion]
      These results demonstrate the high reliability and validity of ultrasound-based
      imaging in the quantitative assessment of lumbar interspinous process distance.
      Of the two methods, the E-E measurement method is recommended. 

PMID- 26311977
TI  - Comparison of the effectiveness of balance training using a reaching task between
      a sitting position and a standing position in the elderly.
AB  - [Purpose] The purpose of this study was to compare the effectiveness of balance
      training using a reaching task between a sitting position and a standing position
      in the elderly. [Subjects and Methods] The study included 30 elderly women from D
      city. The subjects were divided into the following two groups, according to the
      training position: the sitting group (n = 15) and standing group (n = 15). Both
      groups performed training for 20 min, thrice a week for 8 weeks. The short form
      of the berg balance scale (SFBBS), timed 10-m walk test (10MWT), timed up & go
      test (TUG), and falls efficacy scale (FES) were used before and after training.
      [Results] SFBBS, 10MWT, and TUG values were significantly different between
      before and after training in both groups. However, FES values were significantly
      different in only the standing group. [Conclusion] Balance training in a standing
      position is helpful for improving activities that mainly use the lower
      extremities, such as gait, and training in a sitting position is somewhat helpful
      for improving balance ability. In addition, balance training in both positions
      can help overcome the fear of falling. 

PMID- 26311978
TI  - Effects of using an unstable inclined board on active and passive ankle range of
      motion in patients with ankle stiffness.
AB  - [Purpose] The present study assessed the effects of using an unstable inclined
      board on the active and passive ankle range of motion in patients with ankle
      stiffness. [Subjects] The study included 10 young female patients with ankle
      stiffness. [Methods] The patients were divided into the following two groups: a
      group that performed ankle dorsiflexion stretching exercises using a wooden
      inclined board and a group that performed stretching exercises using an air
      cushioned inclined board (unstable inclined board). Active and passive ankle
      dorsiflexion angles were measured bilaterally using a goniometer. [Results] Both
      inclined boards significantly increased active and passive ankle dorsiflexion.
      After performing ankle stretching exercises, active dorsiflexion significantly
      increased the unstable inclined board compared to that using the wooden inclined
      board. However, the passive dorsiflexion angles did not differ significantly
      between the two groups after ankle stretching exercises. [Conclusion] The use of
      an unstable inclined board might stimulate activation of the ankle dorsiflexors
      in addition to stretching muscle or tissue. Active ankle dorsiflexion was more
      effectively improved with stretching exercises using an unstable inclined board
      than with exercises using a wooden inclined board. 

PMID- 26311979
TI  - Comparison of lumbar spinal angle between normal body mass index and overweight
      young adults.
AB  - [Purpose] This study compared the upper and lower lumbar angles of normal body
      mass index and overweight young adults, and examined the relationships among body
      mass index, waist circumferences, and lumbar angles. [Subjects and Methods] Sixty
      participants aged 18-25 years were recruited and allocated to 2 groups (n=30 per
      group): normal body mass index (18.5-24.9 kg/m(2)) and overweight group (body
      mass index, >= 25.0 kg/m(2)). During lumbar angle measurement, the participants
      stood in a relaxed position with bare feet. The upper and lower lumbar angles of
      each participant were measured using a flexible ruler, and the angle calculated
      by the tangent method. The waist circumference was also measured. [Results] The
      mean lower lumbar angle in the overweight group was significantly greater than
      that of the normal body weight group. Moreover, only the lower lumbar angle was
      associated with a significant increase in the body mass index (r=0.28). Waist
      circumference showed no association with the lumbar angles. [Conclusion] This is
      the first study to suggest that increased body weight could cause lower lumbar
      angle deviation in young adults. Further studies should investigate individuals
      with symptomatic back pain or back dysfunction and the impact of body weight on
      lumbar spinal angles. 

PMID- 26311980
TI  - Effects of wearing rubber gloves on activities of the forearm and shoulder
      muscles during different dishwashing stages.
AB  - [Purpose] The present study examined the effects of wearing rubber gloves on the
      activities of the forearm and shoulder muscles during two dishwashing stages.
      [Subjects] This study included 10 young females. [Methods] The participants
      performed two dishwashing stages (washing and rinsing) with and without rubber
      gloves. The activities of the wrist flexor and upper trapezius muscles were
      measured using wireless electromyography. [Results] During the washing stage, the
      activities of the wrist flexor and upper trapezius muscles were significantly
      greater without gloves than with gloves when performing the same tasks. However,
      during the rinsing stage, the activities of these muscles did not differ
      significantly according to the use of gloves. [Conclusion] Dishwashers should
      wear gloves during the washing stage to prevent wrist and shoulder pain. 

PMID- 26311981
TI  - Myogenic cell response to muscle contraction with short electrical stimulation.
AB  - [Purpose] The present study aimed to determine the effects of short muscle
      strength exercise on hepatocyte growth factor expression and satellite cell
      activation. [Subjects] The study included 72 2-12-week-old male Sprague-Dawley
      rats. [Methods] The rat plantaris muscle was contracted with a 5-min electrical
      stimulation of the sciatic nerve, and then, the mRNA expressions of hepatocyte
      growth factor and myogenic regulatory factors in the plantaris muscle were
      determined, and the phosphorylation of the hepatocyte growth factor receptor (c
      Met) was examined. [Results] The mRNA expressions of hepatocyte growth factor and
      myogenic regulatory factors increased after a short muscle contraction compared
      to that un-contraction. Immunofluorescence analysis showed the expression of
      hepatocyte growth factor protein and the possibility that downstream biological
      changes occurred in the hepatocyte growth factor-bound c-Met. [Conclusion] Our
      results demonstrated that activation of satellite cells induced hepatocyte growth
      factor expression during muscle contraction with a short 5-min electrical
      stimulation, which simulates short muscle strength exercise in physical therapy.
      The present study provides evidence for the use of short muscle strength exercise
      in physical therapy. 

PMID- 26311982
TI  - Trunk and pelvic coordination at various walking speeds during an anterior load
      carriage task in subjects with and without chronic low back pain.
AB  - [Purpose] This study compared the coordination patterns of the trunk and pelvis
      in the transverse plane between healthy subjects and patients with chronic low
      back pain during an anterior load carriage task at various walking speeds.
      [Subjects] Ten healthy subjects and 10 patients with chronic low back pain
      performed an anterior carriage task with a load of 10% body weight at walking
      speeds of 3.5, 4.5, or 5.5 km/h. [Methods] The trunk and pelvic kinematics were
      measured by using a motion analysis system. During the anterior carriage task,
      the continuous relative phase differed significantly between groups with respect
      to walking speed. [Results] The continuous relative phase was more anti-phase in
      the chronic low back pain group than the control group. The inter-group
      continuous relative phase pattern was affected by walking at 5.5 km/h.
      [Conclusion] Compared to controls, subjects with chronic low back pain are unable
      to establish an in-phase between the trunk and pelvis from walking at 3.5 to 5.5
      km/h during an anterior carriage task. 

PMID- 26311983
TI  - Visual biofeedback exercises for improving body balance control after anterior
      cruciate ligament reconstruction.
AB  - [Purpose] To evaluate the effects of balance training after arthroscopic anterior
      cruciate ligament reconstruction. [Subjects and Methods] Sixteen patients (mean
      33 +/- 8 years old) who underwent anterior cruciate ligament reconstruction three
      months prior to participating in a one-month rehabilitation program. The control
      group included 15 people aged 34 +/- 4 years. Patients' functional level was
      evaluated according to the Lysholm knee score, and balance quality was
      ascertained by static and dynamic tests. A balance platform was used to measure
      the center of foot pressure deflection. Two dynamic balance tests evaluated time
      of task execution. [Results] Lysholm knee score improved significantly after
      rehabilitation. Balance in the sagittal plane with eyes closed improved
      significantly after rehabilitation. The average velocity of center of foot
      pressure swing in both the frontal and sagittal planes with eyes closed differed
      significantly from those of controls. Execution time required for the two dynamic
      tests decreased significantly after rehabilitation and were significantly better
      than those in the controls. [Conclusion] Maintaining static balance with eyes
      closed is very challenging after anterior cruciate ligament reconstruction.
      Maintaining balance in the sagittal plane is particularly difficult. A one-month
      rehabilitation program partially improves static and dynamic balance. 

PMID- 26311984
TI  - Effects of cervical self-stretching on slow vital capacity.
AB  - [Purpose] This study investigated the effects of self-stretching of cervical
      muscles, because the accessory inspiratory muscle is considered to improve
      pulmonary function. [Subjects] The subjects were 30 healthy university students
      19-21 years old who did not have any lung disease, respiratory dysfunction,
      cervical injury, or any problems upon cervical stretching. [Methods] Spirometry
      was used as a pulmonary function test to measure the slow vital capacity before
      and after stretching. The slow vital capacity of the experimental group was
      measured before and after cervical self-stretching. Meanwhile, the slow vital
      capacity of the control group, which did not perform stretching, was also
      measured before and after the intervention. [Results] The expiratory vital
      capacity, inspiratory reserve volume, and expiratory reserve volume of the
      experimental group increased significantly after the cervical self-stretching.
      [Conclusion] Self-stretching of the cervical muscle (i.e., the inspiratory
      accessory muscle) improves slow vital capacity. 

PMID- 26311985
TI  - Effects of horseback riding exercise therapy on background electroencephalograms
      of elderly people.
AB  - [Purpose] This study investigated the effect of horseback riding exercise on the
      background electroencephalograms of elderly people who performed horseback riding
      for 8 weeks. [Subjects] Twenty elderly people were divided into the horseback
      riding exercise and control group (n = 10 each). [Methods] The exercise was
      performed for 15 minutes, 3 times per week for 8 weeks. Electroencephalograms
      were analyzed. Post-exercise evaluation was performed after 8 weeks. [Results]
      After the horseback riding exercise, the relative slower alpha power index was
      active in the T3 and P4 domains but suppressed in the Fp1, Fp2, F3, F4, T4, and
      P3 domains. Moreover, the relative faster alpha power index was active in all
      domains of the horseback riding exercise group but was suppressed in all domains
      of the control group. There was a significant difference between groups in the F3
      domain. [Conclusion] The alpha power index increased significantly after
      horseback riding exercise, suggesting the exercise improved background
      electroencephalogram. 

PMID- 26311986
TI  - Effects of yoga exercises for headaches: a systematic review of randomized
      controlled trials.
AB  - [Purpose] To assess the evidence for the effectiveness of yoga exercises in the
      management of headaches. [Subjects and Methods] A search was conducted of six
      electronic databases to identify randomized controlled trials (RCTs) reporting
      the effects of yogic intervention on headaches published in any language before
      January 2015. Quality assessment was conducted using the Cochrane risk of bias
      tool. [Results] One potential trial was identified and included in this review.
      The quality critical appraisal indicated a moderate risk of bias. The available
      data could only be included as a narrative description. Headache intensity and
      frequency, anxiety and depression scores, and symptomatic medication use were
      significantly lower in the yoga group compared to the control group. [Conclusion]
      There is evidence from one RCT that yoga exercises may be beneficial for
      headaches. However, the findings should be interpreted with caution due to the
      small number of RCTs. Therefore, further rigorous methodological and high quality
      RCTs are required to investigate the hypothesis that yoga exercises alleviate
      headaches, and to confirm and further comprehend the effects of standardized yoga
      programs on headaches. 

PMID- 26311987
TI  - Facioscapulohumeral distrophy and physiotherapy: a literary review.
AB  - [Purpose] The purpose of this review was to critically evaluate the literature
      concerning the physiotherapy of facioscapulohumeral dystrophy, and to determine
      an effective protocol for physiotherapy treatments, which can be adapted to
      patient characteristics. [Methods] A bibliographic research was carried out of
      research papers held in the following databases: PUBMED, PEDRO, MEDLINE, EDS BASE
      INDEX. The inclusion criteria for acceptance of the studies to the review were
      randomized controlled trials (RCTs) concerning a sample no smaller than 10 people
      and a medium- or long-term report of the results achieved. [Results] Just six of
      the works satisfied the inclusion criteria, and just three of them were useful
      for the review. However, these studies were difficult to compare. [Conclusion] At
      present, there are few studies concerning facioscapulohumeral dystrophy in the
      literature, and the few that are available rule out the utility of the techniques
      used. Therefore, more RCTs of new treatment strategies are needed. 

PMID- 26311988
TI  - Effectiveness of therapeutic physical exercise in the treatment of patellofemoral
      pain syndrome: a systematic review.
AB  - [Purpose] The aim of this study was to analyze the effectiveness of conservative
      treatment of patellofemoral pain syndrome with physical exercise. [Subjects and
      Methods] A computer-based review conducted of four databases (PubMed, the
      Cochrane Library, PEDro, and the University Library) was completed based on the
      inclusion criteria of patellofemoral pain syndrome patients treated with physical
      exercise methods and examination with self-reported pain and/or functional
      questionnaires. [Results] The findings of ten clinical trials of moderate to high
      quality were evaluated to determine the effectiveness of physical exercise as
      conservative management for patellofemoral pain syndrome. [Conclusion] The
      intervention programs that were most effective in relieving pain and improving
      function in patellofemoral pain syndrome included proprioceptive neuromuscular
      facilitation stretching and strengthening exercises for the hip external rotator
      and abductor muscles and knee extensor muscles. 

PMID- 26311989
TI  - Comparison of quality of life according to community walking in stroke patients.
AB  - [Purpose] The aim of this study was to examine the quality of life of stroke
      patients according to their degree of community walking. [Subjects] This study
      utilized raw data from the sixth Korea National Health and Nutrition Examination
      Survey conducted in 2013 by the Korea Centers for Disease Control and Prevention.
      The subjects were noninstitutionalized stroke patients (n = 71) diagnosed by a
      doctor. [Methods] Trained surveyors visited households selected for the sample
      and conducted face-to-face interviews in conjunction with a structured
      questionnaire. The content of the interview included demographic data and the
      EuroQoL; EQ-5D-3L. Inferential statistical analysis took into account the
      clustering and stratification of the sample survey data as usually done in a
      complex survey design. A chi(2) test was performed to identify the quality of
      life distribution according to walking days during a typical week. Finally,
      logistic regression analysis was performed to identify the correlation between
      quality of life and walking days. [Results] Mobility, usual activities, and
      anxiety/depression differed significantly according to number of walking days
      during a normal week. No significant difference was found in the relationship
      between quality of life and days of walking during a normal week. [Conclusion]
      This study indicates that community walking every day is better than walking 1-3
      days a week or no walking in terms of the effect on quality of life. However, the
      extent to which community walking is good for improving quality of life is
      unclear. Further studies need to determine the optimal duration (days) of
      community walking. 

PMID- 26311990
TI  - The use of McConnell taping to correct abnormal biomechanics and muscle
      activation patterns in subjects with anterior knee pain: a systematic review.
AB  - [Purpose] The aim of this review was to present the available evidence for the
      effect of McConnell taping on knee biomechanics in individuals with anterior knee
      pain. [Methods] The PubMed, Medline, Cinahl, SPORTDiscus, PEDro and ScienceDirect
      electronic databases were searched from inception until September 2014.
      Experimental research on knee biomechanical or EMG outcomes of McConnell taping
      compared with no tape or placebo tape were included. Two reviewers completed the
      searches, selected the full text articles, and assessed the risk of bias of
      eligible studies. Authors were contacted for missing data. [Results] Eight
      heterogeneous studies with a total sample of 220 were included in this review.
      All of the studies had a moderate to low risk of bias. Pooling of data was
      possible for three outcomes: average knee extensor moment, average VMO/VL ratio
      and average VMO-VL onset timing. None of these outcomes revealed significant
      differences. [Conclusion] The evidence is currently insufficient to justify
      routine use of the McConnell taping technique in the treatment of anterior knee
      pain. There is a need for more evidence on the aetiological pathways of anterior
      knee pain, level one evidence, and studies investigating other potential
      mechanisms of McConnell taping. 

PMID- 26311991
TI  - Ankle inversion taping using kinesiology tape for treating medial ankle sprain in
      an amateur soccer player.
AB  - [Purpose] The purpose of this study was to report the effects of ankle inversion
      taping using kinesiology tape in a patient with a medial ankle sprain. [Subject]
      A 28-year-old amateur soccer player suffered a Grade 2 medial ankle sprain during
      a match. [Methods] Ankle inversion taping was applied to the sprained ankle every
      day for 2 months. [Results] His symptoms were reduced after ankle inversion
      taping application for 2 months. The self-reported function score, the reach
      distances in the Star Excursion Balance Test, and the weight-bearing ankle
      dorsiflexion were increased. [Conclusion] This study showed that ankle inversion
      taping using kinesiology tape may be an effective therapy for a patient with a
      medial ankle sprain. 

PMID- 26311992
TI  - Squat exercise to estimate knee megaprosthesis rehabilitation: a pilot study.
AB  - [Purpose] This study evaluated a specific rehabilitation protocol using a half
      squat after total knee reconstruction with distal femur megaprosthesis and tibial
      allograft-prosthesis composite. [Subject and Methods] Squat execution was
      recorded by a three-dimensional system before and after a specific rehabilitation
      program on a 28-year-old patient. Squat duration, body center of mass trajectory,
      and vertical range of motion were determined. Step width and joint angles and
      symmetry (hip flexion, extension, and rotation, knee flexion, and ankle dorsal
      and plantar flexion) were estimated. Knee and hip joint symmetry was computed
      using a bilateral cyclogram technique. [Results] After rehabilitation, the squat
      duration was longer (75%), step width was similar, and vertical displacement was
      higher. Hip flexion increased by over 20%, and ankle dorsiflexion diminished by
      14%. The knee had the highest symmetry gain (4.1-3.4%). Angle-angle plot
      subtended areas decreased from 108 degrees  to 40 degrees (2) (hip) and from 204
      degrees  to 85 degrees (2) (knee), showing improvement in movement symmetry.
      [Conclusion] We concluded that the squat is an effective multifactorial exercise
      to estimate rehabilitation outcomes after megaprosthesis, also considering that
      compressive and shear forces are minimal up to 60-70 degrees  of knee flexion. 

PMID- 26311993
TI  - Are we moving towards a new definition of essential medicines?

PMID- 26311994
TI  - Inhaled insulin: A "puff" than a "shot" before meals.
AB  - Diabetes is a metabolic disorder characterized by relative or absolute deficiency
      of insulin, resulting in hyperglycemia. The main treatment of diabetes relies on
      subcutaneous insulin administration by injection or continuous infusion to
      control glucose levels, besides oral hypoglycemic agents for type 2 diabetes.
      Novel routes of insulin administration are an area of research in the diabetes
      field as insulin injection therapy is burdensome and painful for many patients.
      Inhalational insulin is a potential alternative to subcutaneous insulin in the
      management of diabetes. The large surface area, good vascularization, immense
      capacity for solute exchange and ultra-thinness of the alveolar epithelium
      facilitates systemic delivery of insulin via pulmonary administration. Inhaled
      insulin has been recently approved by Food and Drug Administration (FDA). It is a
      novel, rapid-acting inhaled insulin with a pharmacokinetic profile that is
      different from all other insulin products and comparatively safer than the
      previous failed inhaled insulin (Exubera). 

PMID- 26311995
TI  - Comparison of anti-inflammatory effect of atorvastatin with rosuvastatin in
      patients of acute coronary syndrome.
AB  - OBJECTIVES: To compare anti-inflammatory effect of atorvastatin and rosuvastatin
      in patients of acute coronary syndrome. MATERIALS AND METHODS: The study was a
      prospective, open-labeled, randomized and single-center study conducted on 100
      patients of acute coronary syndrome. Patients were assigned to atorvastatin 40 mg
      daily or rosuvastatin 20 mg daily for 4 weeks. C-reactive protein (CRP) levels,
      lipid profiles, erythrocyte sedimentation rate (ESR) and adverse effects were
      measured at beginning and at the end of 4 weeks. RESULTS: Baseline parameters and
      clinical profile did not differ between the two groups. CRP levels significantly
      decreased from beginning to the end of 4 weeks in both atorvastatin and
      rosuvastatin groups (from 35.48 to 23.07 mg/l and from 35.88 to 19.91 mg/l
      respectively, both P < 0.001). However, there was significant difference between
      the levels of CRP in patients of the rosuvastatin group as compared to the
      atorvastatin group (19.91 +/- 6.32 vs 23.07 +/- 7.47, P < 0.05). In addition,
      both the drugs were associated with a reduction in total cholesterol, LDL levels
      and ESR at the end of 4 weeks as compared to the beginning (P < 0.001 for all
      comparisons). CONCLUSION: Both atorvastatin (40 mg) and rosuvastatin (20 mg) are
      effective in decreasing CRP and LDL cholesterol levels even in a short duration
      of 4 weeks. Rosuvastatin was found to be more effective in decreasing CRP levels.

PMID- 26311996
TI  - Inhibition by sildenafil of contractility of isolated non-pregnant human
      myometrium.
AB  - OBJECTIVE: To investigate the ability of sildenafil to inhibit the contractility
      of isolated non pregnant human myometrium. MATERIALS AND METHODS: The inhibitory
      effect of three concentrations (3, 10, and 30 uM) of sildenafil on 55 mM KCl
      induced contractility of isolated non-pregnant human myometrium was studied. The
      ability of the guanylyl cyclase inhibitor ODQ (10 uM), the adenylyl cyclase
      inhibitor MDL-12,330A (10 uM), the non-specific potassium channel blocker TEA (2
      mM), and the calcium-sensitive potassium (BKCa) channel blocker iberiotoxin (100
      nM) to reverse the inhibition of 10 uM sildenafil on KCl-induced myometrial
      contractility was also studied. RESULTS: Sildenafil produced a concentration
      dependent inhibition of KCl-induced myometrial contractility that was
      statistically significant at all three concentrations of sildenafil used. The
      inhibition by 10 uM sildenafil of KCl-induced myometrial contractility was not
      reversed by the concurrent administration of ODQ or MDL-12,330A. The inhibition
      of 10 uM sildenafil of myometrial contractility was partially reversed by
      concurrent administration of TEA and totally and significantly reversed by the
      concurrent administration of iberiotoxin. CONCLUSIONS: These results suggest that
      sildenafil inhibits the contractility of isolated non-pregnant human myometrium.
      The results suggest that sildenafil does so by opening BKCa channels.

PMID- 26311997
TI  - Effectiveness of vitamin D3 in severe persistent asthmatic patients: A double
      blind, randomized, clinical study.
AB  - OBJECTIVE: To assess the pulmonary function and quality of life in asthma
      patients receiving vitamin D3 supplementation with inhaled budesonide and
      formoterol. MATERIALS AND METHODS: This was a double blinded, randomized,
      comparative study. Patients were recruited as per the study criteria and
      randomized into two groups: usual care group (n = 69) patients received
      budesonide (800 MUg) with formoterol (24 MUg) and intervention care group (n =
      72) patients received vitamin D3 (1000 IU) supplementation along with budesonide
      (800 MUg) plus formoterol (24 MUg) for a period of 6 months. RESULTS: A total of
      140 patients completed the study. Significant within-group improvement and non
      significant between-group improvement is observed with respect to FEV1. In terms
      of health-related quality of life, within-group comparison revealed a significant
      (P < 0.05) improvement in all the domains of SGRQ. However, between-group
      comparisons showed statistically significant (P < 0.05) improvement in symptom,
      impact and total scores. CONCLUSION: On the basis of our findings, we conclude
      that supplementation of vitamin D3 is effective in improving the quality of life
      rather than pulmonary function in severe asthmatics. However, further studies are
      warranted to substantiate the present findings.

PMID- 26311998
TI  - The effects of A2B receptor modulators on vascular endothelial growth factor and
      nitric oxide axis in chronic cyclosporine nephropathy.
AB  - INTRODUCTION: To investigate the actions of adenosine A2B receptor modulators on
      VEGF and NO levels in CsA nephropathy. MATERIALS AND METHODS: Nephropathy was
      induced by administrating 25 mg/kg (s.c) of CsA for 5 weeks. The VEGF and NO
      levels were measured in kidney tissue. Serum creatinine, creatinine clearance,
      urinary albumin excretion, blood urea nitrogen, kidney pathology score were
      measured to assess renal function. The analysis of mRNA expression of A2B
      receptor and VEGF was performed. RESULTS: Administration of CsA for 5 weeks
      induced adverse renal function. The mRNA expression of VEGF was reduced in renal
      tissue after 5 weeks of CsA treatment. The renal VEGF and NO levels were also
      reduced in these animals. In vivo administration of A2B adenosine receptor
      agonist increased renal VEGF which was inhibited by a selective A2B AR antagonist
      (MRS1754) in CsA-treated animals. The increase in VEGF was associated with
      reversal of adverse renal functions. The effects of A2B AR modulators were
      prominent in CsA-treated animals compared with control animals suggesting CsA
      treatment may upregulate A2B ARs. The mRNA expression of A2B AR was increased
      after 5 weeks of CsA. CONCLUSIONS: A2B AR modulators may provide new therapeutic
      options to retard CsA nephropathy by mediating renal VEGF and NO.

PMID- 26311999
TI  - Identification and characterization of primate P-glycoprotein.

PMID- 26312000
TI  - Therapeutic drug monitoring of modified release once daily tacrolimus in de novo
      renal transplant with conversion to a twice daily generic in the stable period.

PMID- 26312001
TI  - Double trouble: Cyclosporine-induced thrombocytosis in a patient with
      methotrexate toxicity: Are they related?
AB  - Psoriasis is a common, chronic, disfiguring, inflammatory, and proliferative
      condition of the skin. It manifests with varying degrees of severity and can be
      treated with various immune modulators. This is a case report of a 57-year-old
      male patient of psoriasis on long-term oral methotrexate, who developed
      methotrexate toxicity when given an injection of methotrexate for unstable
      psoriasis. After recovery, the patient was started on cyclosporine 100 mg twice a
      day. After a week, he developed thrombocytosis, which reverted a week after
      cyclosporine was stopped. The patient is currently being managed with acitretin.
      The aim of this case report is to emphasize the various unpredictable adverse
      reactions encountered during treatment of psoriasis, especially when a
      combination or sequential treatment is used. There is a need for caution, as late
      sequelae of long-term administration of the systemic agents used in the treatment
      of psoriasis are still unknown. 

PMID- 26312002
TI  - Exercise-induced anaphylaxis and antileukotriene montelukast.
AB  - We report a rare case of exercise-induced anaphylaxis (EIA), occurring
      exclusively with exercise, without any other associated trigger, detected in the
      prodromal phase, and prevented from additional anaphylaxis episodes by treatment
      with cetirizine and 10 mg daily of antileukotriene montelukast to date. EIA is a
      syndrome in which patients experience a spectrum of the symptoms of anaphylaxis
      ranging from mild cutaneous signs to severe systemic manifestations such as
      hypotension, syncope, and even death after increased physical activity. Many
      people have triggers, such as, a variety of foods, various medications, alcohol,
      cold weather, humidity, and seasonal and hormonal changes along with exercise
      that cause the symptoms. Typically, either exercise or the specific trigger alone
      will rarely cause symptoms. It is differentiated from cholinergic urticaria by
      the absence of response to passive body warming and emotional stress. 

PMID- 26312003
TI  - Nebivolol-induced gynecomastia.
AB  - Adverse drug reactions play a substantial role in the etiology of gynecomastia.
      Gynecomastia as an adverse drug reaction, related to some cardiovascular drugs,
      has been reported in literature. Nebivolol is a third generation beta-blocker,
      and gynecomastia as an adverse effect on the consumption of this drug has not
      been reported in any article yet. We herein present the case of a 42-year-old
      male, who developed bilateral gynecomastia following nebivolol use and complete
      regression after discontinuation of nebivolol. Other reasons causing gynecomastia
      were excluded. Discontinuation of the responsible drug is quite sufficient with
      regard to the treatment of drug-induced gynecomastia, without any pharmacological
      or surgical treatment. 

PMID- 26312004
TI  - Intestinal pseudo-obstruction following oral baclofen: An unusual complication.
AB  - Baclofen is a gamma- aminobutyric acid B (GABA B) agonist used for the management
      of spasticity associated with spinal cord injury. Oral baclofen might cause
      constipation, but intestinal pseudo-obstruction is very rare. We report a 50-year
      old male with spasticity following cervical discectomy (C3-4) on oral baclofen
      for 6 months with intestinal pseudo-obstruction. He had undergone open suprapubic
      cystostomy for traumatic urethral injury, 45 days prior to the presentation and
      adhesive intestinal obstruction was also considered a possibility. However, there
      were no air fluid levels on abdominal radiographs and ultrasound abdomen was non
      contributory. Withdrawal of baclofen was therapeutic in this patient. This case
      is being reported to highlight the rare possibility of oral baclofen induced
      intestinal pseudo-obstruction. 

PMID- 26312005
TI  - Acalculous pyelonephritis and cholecystitis occurring simultaneously in a
      diabetic patient on sitagliptin therapy.
AB  - Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of anti-diabetic drugs.
      They control both fasting and postprandial hyperglycemia by inhibiting
      degradation of incretin hormones, such as, glucagon-like peptide-1(GLP-1) and
      glucose-dependent insulinotropic polypeptide (GIP). Sitagliptin is the first DPP
      4 inhibitor to be marketed in India. In addition to its glucose lowering effect,
      it also suppresses immunity resulting in various infections in a diabetes
      patient. Here, we describe the simultaneous development of two infections
      (acalculous pyelonephritis and cholecystitis) in a postmenopausal female patient,
      well-controlled on sitagliptin-based anti-diabetic therapy. 

PMID- 26312006
TI  - Complete resistance after maximal dose of rocuronium.
AB  - Rocuronium is a non-depolarizing neuromuscular blocking agent (NDNMBA), employed
      in the clinic as an adjunct to general anesthesia to facilitate tracheal
      intubation rapid sequence, and to provide skeletal muscle relaxation during
      surgery. Many cases of resistance to neuromuscular blocking agents (NMBAs) have
      been anecdotally reported. There are specific pathologic states, such as upper
      motor neuron lesions, severe thermal injuries, liver disease, renal failure,
      disuse atrophy, all of which show an increased resistance to the effects of
      nondepolarizing muscle relaxants. Also concurrent drug therapy can alter the
      efficacy of NMBAs such as some classes of antibiotics, furosemide, beta receptor
      agonists, phosphodiesterase inhibitors, calcium antagonists, respiratory
      stimulants but also ketamine, propofol and barbiturates at high concentrations.
      In this scenario we describe an unusual case of 20-years-old man who showed a
      complete resistance to rocuronium maybe due to a glucocorticoids concomitant
      therapy. 

PMID- 26312007
TI  - Life-threatening bradyarrhythmia with oral phenytoin overdose.
AB  - We report a case of a 41-year-old lady, who developed severe hypotension and
      sinus bradycardia, following oral consumption of 20 g of phenytoin and 500 mg of
      glibenclamide. She required high dose of inotropes and a temporary transvenous
      pacer for her hemodynamic instability. This life-threatening cardiotoxicity of
      phenytoin could have been due to its interaction with sulphonylurea. It is
      imperative to be aware of drug interactions, due to which, life-threatening
      cardiovascular manifestations following phenytoin toxicity can occur. 

PMID- 26312008
TI  - Prescription errors in cancer chemotherapy: Omissions supersede potentially
      harmful errors.

PMID- 26312009
TI  - Authors' reply.

PMID- 26312010
TI  - International conference on harmonization of technical requirements for
      registration of pharmaceuticals for human use.

PMID- 26312011
TI  - Naloxegol: First oral peripherally acting mu opioid receptor antagonists for
      opioid-induced constipation.
AB  - Opioid-induced constipation (OIC) is one of the most troublesome and the most
      common effects of opioid use leading to deterioration in quality of life of the
      patients and also has potentially deleterious repercussions on adherence and
      compliance to opioid therapy. With the current guidelines advocating liberal use
      of opioids by physicians even for non-cancer chronic pain, the situation is
      further complicated as these individuals are not undergoing palliative care and
      hence there cannot be any justification to subject these patients to the severe
      constipation brought on by opioid therapy which is no less debilitating than the
      chronic pain. The aim in these patients is to prevent the opioid-induced
      constipation but at the same time allow the analgesic activity of opioids. Many
      drugs have been used with limited success but the most specific among them were
      the peripherally acting mu opioid receptor antagonists (PAMORA). Methylnaltrexone
      and alvimopan were the early drugs in this group but were not approved for oral
      use in OIC. However naloxegol, the latest PAMORA has been very recently approved
      as the first oral drug for OIC. This article gives an overview of OIC, its
      current management and more specifically the development and approval of
      naloxegol, including pharmacokinetics, details of various clinical trials,
      adverse effects and its current status for the management of OIC. 

PMID- 26312012
TI  - Erratum: Stevens-Johnson syndrome caused by Cefepime: Erratum.
AB  - [This corrects the article on p. 35 in vol. 6, PMID: 25709351.]. 

PMID- 26312013
TI  - The Use of Peer Networks to Increase Communicative Acts of First Grade Students
      with Autism Spectrum Disorders.

PMID- 26312014
TI  - mTOR signaling in mice with dysfunctional cardiac ryanodine receptor ion channel.
AB  - Simultaneous substitution of three amino acid residues in the calmodulin binding
      domain (W3587A/L3591D/F3603A, ADA) of the cardiac ryanodine receptor ion channel
      (RyR2) impairs calmodulin inhibition of RyR2 and causes cardiac hypertrophy and
      early death of Ryr2ADA/ADA mice. To determine the physiological significance of
      growth promoting signaling molecules, the protein and phosphorylation levels of
      Ser/Thr kinase mTOR and upstream and downstream signaling molecules were
      determined in hearts of wild-type and Ryr2ADA/ADA mice. Phosphorylation of mTOR
      at Ser-2448, and mTOR downstream targets p70S6 kinase at Thr-389, S6 ribosomal
      protein at Ser-240/244, and 4E-BP1 at Ser-65 were increased. However, there was
      no increased phosphorylation of mTOR upstream kinases PDK1 at Ser-241, AKT at Thr
      308, AMPK at Thr-172, and ERK1/2 at Thr-202/Tyr204. To confirm a role for mTOR
      signaling in the development of cardiac hypertrophy, rapamycin, an inhibitor of
      mTOR, was injected into wild-type and mutant mice. Rapamycin decreased mouse
      heart-to-body weight ratio, improved cardiac performance, and decreased
      phosphorylation of mTOR and downstream targets p70S6K and S6 in 10-day-old
      Ryr2ADA/ADA mice but did not extend longevity. Taken together, the results link a
      dysfunctional RyR2 to an altered activity of signaling molecules that regulate
      cardiac growth and function.

PMID- 26312015
TI  - Long-Term Effects of Childhood Risk Factors on Cardiovascular Health During
      Adulthood.
AB  - The primary purpose of this article is to provide a broad overview of the
      research on the long-term effects of childhood risk factors on cardiovascular
      diseases (CVDs) during adulthood and to outline recommendations for prevention of
      CVDs based on evidence-based interventions (EBIs). CVDs are the leading cause of
      death and a major cause of disability in the United States and globally. Risk
      factors for CVDs are already identifiable in children and youth, and include both
      modifiable factors (e.g., unhealthy diet, physical inactivity, tobacco smoking),
      and factors that cannot be changed (e.g., age, heredity, sex). A fundamental
      issue has been the severity of the long-term effects of childhood risk factors
      (i.e., behavioral and intermediate risk factors) on subsequent cardiovascular
      health. It is clear from the empirical evidence that risk factors for CVDs can
      develop during childhood and adolescence. These risk factors in childhood have
      been linked to adverse health outcomes, including CVDs, during adulthood. The
      findings thus far suggest that, in order to be effective and reduce the risk of
      adulthood CVDs, intervention strategies should begin during childhood. The
      findings also underscore the importance of adopting a healthy lifestyle as early
      in life as possible.

PMID- 26312016
TI  - Three new species of the genus Aporcelaimoides Heyns, 1965 from Vietnam
      (Nematoda, Dorylaimida, Aporcelaimidae), with an updated taxonomy of the genus.
AB  - Three new species of Aporcelaimoides from natural habitats in Vietnam are
      studied, described and illustrated, including line drawings, LM and/or SEM
      pictures. Aporcelaimoidesbrevistylum sp. n. is characterized by its body 1.95
      2.90 mm long, lip region offset by deep constriction and 17-18 um broad, ventral
      side of mural odontostyle 11-14 um long with aperture occupying 62-71% of its
      length, neck 663-767 um long, pharyngeal expansion occupying 58-66% of total neck
      length, uterus a simple tube 85-182 um long, pars refringens vaginae absent, V =
      55-63, tail short and rounded (34-46 um, c = 49-76, c' = 0.6-0.8), spicules 67-86
      um long, and one ventromedian supplement out the range of spicules.
      Aporcelaimoidesminor sp. n. is distinguished in having body 2.09-2.61 mm long,
      lip region offset by deep constriction and 19-20 um broad, mural odontostyle 14
      16 um long at its ventral side with aperture occupying 73-84% of its length, neck
      579-649 um long, pharyngeal expansion occupying 57-66% of total neck length,
      uterus a simple tube 44-69 um long, pars refringens vaginae well developed, V =
      48-56, female tail very short, rounded conoid or truncate (14-26 um, c = 90-146,
      c' = 0.3-0.6), and male unknown. Aporcelaimoidessilvaticum sp. n. is
      characterized by its body 2.09-2.60 mm long, lip region offset by depression and
      17-18 um broad, mural odontostyle 11-12 um long at its ventral side with aperture
      occupying 60-66% of its length, neck 597-720 um long, pharyngeal expansion
      occupying 58-64% of total neck length, uterus a simple tube 128-243 um long, pars
      refringens vaginae well developed, V = 58-60, tail short and rounded (27-37 um, c
      = 67-94, c' = 0.6-0.7), spicules 64-75 um long, and two or three widely spaced
      ventromedian supplements bearing hiatus. The genus Aporcelaimoides is restored,
      its diagnosis emended, and three species of Sectonema, namely
      Sectonemaamazonicum, Sectonemahaguei and Sectonemamoderatum, transferred to it.
      An updated list of its species, a key to their identification and a tabular
      compendium with the most important morphometric features are also presented. 

PMID- 26312017
TI  - A new genus of water mites (Acari, Hydrachnidia, Wettinidae) from bromeliad
      phytotelmata in the Brazilian Atlantic rainforest.
AB  - Adults of Bromeliacaruscardoso gen. n., sp. n. are described from phytotelmata of
      Quesneliaarvensis (Vellozo) Mez. (Bromeliaceae) in the subtropical area of the
      Atlantic rainforest, Sao Paulo State, Brazil. The new genus Bromeliacarus is
      proposed and diagnosed, based primarily on the autapomorphic presence of 7-9
      pairs of acetabula flanking the gonopore. A possible relationship between
      Bromeliacarus and other Wettinidae are discussed. 

PMID- 26312018
TI  - A contribution to Asian Afidentula Kapur (Coleoptera, Coccinellidae,
      Epilachnini).
AB  - Two new species of Afidentula, Afidentuladentata sp. n. and
      Afidentulajinpingensis sp. n. are described from China. Afissasiamensis Dieke is
      moved to Afidentula comb. n.. All three species are described and illustrated,
      and a distribution map is given. A key to Asian species of Afidentula is updated.
      Diagnostic similarities and differences between Afidentula and Afidenta are
      discussed and illustrated. 

PMID- 26312019
TI  - Three new species and distributional records for Paramaronius Wittmer
      (Coleoptera, Cantharidae, Chauliognathinae).
AB  - Three new species of Paramaronius Wittmer from southeastern Brazil are described
      and illustrated: Paramaroniusserranus sp. n., Paramaroniusbrancuccii sp. n. and
      Paramaroniuscavipennis sp. n. Paramaroniusimpressipennis (Pic) is redescribed,
      with supplementary description of the female. This species is recorded from
      Northeastern Brazil for the first time and its distribution pattern is discussed.
      A distribution map of Paramaronius in South America is provided. An
      identification key to all known species of the genus as well as photographs are
      given. 

PMID- 26312020
TI  - A new species of Noblella (Amphibia, Anura, Craugastoridae) from the humid
      montane forests of Cusco, Peru.
AB  - A new species of Noblella is described from the humid montane forest of the
      Region Cusco in Peru. Specimens were collected at 2330-2370 m elevation in Madre
      Selva, near Santa Ana, in the province of La Convencion. The new species is
      readily distinguished from all other species of Noblella by having a broad,
      irregularly shaped, white mark on black background on chest and belly. The new
      species further differs from known Peruvian species of Noblella by the
      combination of the following characters: tympanic membrane absent, small
      tubercles on the upper eyelid and on dorsum, tarsal tubercles or folds absent,
      tips of digits not expanded, no circumferential grooves on digits, dark brown
      facial mask and lateral band extending from the tip of the snout to the inguinal
      region. The new species has a snout-to-vent length of 15.6 mm in one adult male
      and 17.6 mm in one adult female. Like other recently described species in the
      genus, this new Noblella inhabits high-elevation forests in the Andes and likely
      has a restricted geographic distribution. 

PMID- 26312021
TI  - A snail in the long tail: a new Plekocheilus species collected by the 'Comision
      Cientifica del Pacifico' (Mollusca, Gastropoda, Amphibulimidae).
AB  - Among the historical collection gathered by the 'Comision Cientifica del
      Pacifico' during 1862-1865, type material was found of one of the species
      described on the basis of the material collected shortly afterwards. Inspection
      of the types revealed that only one specimen may be considered as type material
      of Bulimusaristaceus Crosse, 1869; this specimen is now designated as the
      lectotype. The other specimens are described as a new species, Plekocheilus
      (Plekocheilus) cecepeus. 

PMID- 26312022
TI  - Description of a new species of Petrolisthes in the Indo-West Pacific with a
      redefinition of P.hastatus Stimpson, 1858 and resurrection of P.inermis (Heller,
      1862) (Crustacea, Anomura, Porcellanidae).
AB  - The porcellanid crab Petrolistheshastatus Stimpson, 1858, has been traditionally
      viewed as a highly variable species with a wide distribution in the West Pacific.
      For more than a century there has been taxonomic confusion of this species with
      morphologically similar taxa, some of which were synonymized with Stimpson's
      taxon. We redefine Petrolistheshastatus, resurrect Petrolisthesinermis as a valid
      species, discuss the status of Petrolisthestenkatei De Man, 1893, and describe a
      new species as Petrolistheselegantissimus from Indonesia. 

PMID- 26312023
TI  - Descriptions of two new species of Aelurillus Simon, 1884 (Araneae, Salticidae)
      from the Mediterranean, with the synonymization of A.steliosi Dobroruka, 2002.
AB  - Two Aelurillus species are described as new, Aelurillusalboclypeus sp. n. (??,
      from Turkey) and Aelurillusdeltshevi sp. n. (?, from Macedonia, Bulgaria and
      Azerbaijan). Aelurillussteliosi Dobroruka, 2002 is synonymized with
      Aelurillusleipoldae (Metzner, 1999). Additional distributions of the closely
      related species Aelurillusv-insignitus are provided for the region of study.
      Distributional maps are provided for the five species reported in this paper. 

PMID- 26312024
TI  - The spider family Filistatidae (Araneae) in Iran.
AB  - All species of Filistatidae occurring in Iran are surveyed. Zaituniaakhanii sp.
      n. is described on the basis of female specimens collected in Tehran province,
      and the previously unknown male of Sahastatasinuspersica Marusik, Zamani &
      Mirshamsi, 2014 is described for the first time. Also, the endogynes of the
      holotypes of Zaituniaalexandri Brignoli, 1982, Zaituniamedica Brignoli, 1982 and
      Zaituniapersica Brignoli, 1982 are illustrated. Including these results, the
      number of Iranian species of Filistatidae is increased to seven, which indicates
      the highest species-richness of this family in the Western Palaearctic. 

PMID- 26312025
TI  - Scleractinian corals (Fungiidae, Agariciidae and Euphylliidae) of Pulau Layang
      Layang, Spratly Islands, with a note on Pavonamaldivensis (Gardiner, 1905).
AB  - Layang-Layang is a small island part of an oceanic atoll in the Spratly Islands
      off Sabah, Malaysia. As the reef coral fauna in this part of the South China Sea
      is poorly known, a survey was carried out in 2013 to study the species
      composition of the scleractinian coral families Fungiidae, Agariciidae and
      Euphylliidae. A total of 56 species was recorded. The addition of three
      previously reported coral species brings the total to 59, consisting of 32
      Fungiidae, 22 Agariciidae, and five Euphylliidae. Of these, 32 species are new
      records for Layang-Layang, which include five rarely reported species, i.e., the
      fungiids Lithophyllonranjithi, Podabaciasinai, Sandalolithaboucheti, and the
      agariciids Leptoseriskalayaanensis and Leptoseristroglodyta. The coral fauna of
      Layang-Layang is poor compared to other areas in Sabah, which may be related to
      its recovery from a crown-of-thorns seastar outbreak in 2010, and its low habitat
      diversity, which is dominated by reef slopes consisting of steep outer walls.
      Based on integrative molecular and morphological analyses, a Pavona variety with
      small and extremely thin coralla was revealed as Pavonamaldivensis. Since
      specimens from Sabah previously identified as Pavonamaldivensis were found to
      belong to Pavonaexplanulata, the affinities and distinctions of Pavonamaldivensis
      and Pavonaexplanulata are discussed. 

PMID- 26312026
TI  - Lampropsdonghaensis sp. n. (Crustacea, Cumacea, Lampropidae), a new species from
      Korean waters.
AB  - A new species of Cumacea belonging to the genus Lamprops Sars was collected from
      the East Sea of Korea. This new species resembles Lampropscomatus Zimmer,
      Lampropscarinatus Hart, Lampropsflavus Harada, Lampropspumilio Zimmer,
      Lampropstomalesi Gladfelter, and Lampropsobfuscatus (Gladfelter) in lacking
      lateral oblique ridges on the carapace and lateral setae on the telson. The new
      species, however, is distinguished from its congeners by having a dorsal concave
      groove and a lateral rounded depressed area on pereonite 2. The new species is
      fully illustrated and compared with related species. A key to the world Lamprops
      species lacking lateral ridges on the carapace is also provided. 

PMID- 26312027
TI  - Review of the green lacewing genus Chrysacanthia Lacroix with a new species from
      Nigeria (Neuroptera, Chrysopidae).
AB  - The genus Chrysacanthia Lacroix (Chrysopidae: Belonopterygini) is reviewed and a
      new species is described from Nigeria. With the addition of the new species
      described herein, the genus contains four Old World species known from
      Madagascar, Nigeria, India, Thailand and China. 

PMID- 26312028
TI  - Review of the planthopper genus Neodurium Fennah, 1956 (Hemiptera, Fulgoromorpha,
      Issidae).
AB  - The planthopper genus Neodurium Fennah is reviewed and Neoduriumfennahi Chang &
      Chen, sp. n. (Hemiptera: Fulgoromorpha: Issidae) from China (Yunnan), is
      described and illustrated. A checklist of the species of Neodurium is given and a
      key provided for their separation. The female genitalia of Neodurium species are
      described for the first time. 

PMID- 26312029
TI  - New species and new records in Cerambycidae (Coleoptera) of the state of Bahia,
      Brazil.
AB  - Two new species are described from Bahia (Brazil): Coleoxestiabeckeri
      (Cerambycini), and Oncioderesobliqua (Onciderini). Nine species are recorded for
      the first time for Bahia (Brazil). Key to species of Oncioderes Martins &
      Galileo, 1990 is provided. Coleoxestiabeckeri is included in a previous key. 

PMID- 26312030
TI  - A new species of Monoliropus Mayer, 1903 (Crustacea, Amphipoda, Caprellidae) from
      Korean waters.
AB  - A new species of the genus Monoliropus belonging to the family Caprellidae was
      collected from the Yellow Sea, Korea. The new species differs from
      Monoliropusagilis Mayer, 1903, Monoliropuskazemii Momtazi & Sari, 2013, and
      Triprotellaamica Arimoto, 1970 as follows: 1) gnathopod 1 subrectangular; 2)
      pereonites 2-3 with acute triangular processes anterolaterally; 3) mandibular
      palp, apical article with four simple setae subdistally. The new species is fully
      illustrated and extensively compared with related species. This is the first
      record of the genus Monoliropus from Korean waters. A key to Monoliropus species
      is also given. 

PMID- 26312031
TI  - Two new cave-dwelling species of the millipede genus Paracortina Wang & Zhang,
      1993 from southern China (Diplopoda, Callipodida, Paracortinidae).
AB  - Two new species of the millipede genus Paracortina Wang & Zhang, 1993 are
      described. Both are presumed troglophiles: Paracortinazhangi sp. n. from a cave
      in Ceheng County, southwestern Guizhou Province and Paracortinayinae sp. n. from
      a cave in Longlin County, western Guangxi Zhuang Autonomous Region. A
      distribution map and a key to all 12 Paracortina species are also provided. 

PMID- 26312032
TI  - A new genus and species of dalodesmid millipede from New South Wales, Australia
      (Diplopoda, Polydesmida, Dalodesmidae).
AB  - Cernethiainopinata gen. n., sp. n. is described from highland New South Wales.
      Like other dalodesmids the new species has numerous sphaerotrichomes on the legs
      of adult males, but Cernethiainopinata sp. n. shares several character states
      with Tasmanian species in the genera Noteremus Mesibov, 2009, Paredrodesmus
      Mesibov, 2003 and Procophorella Mesibov, 2003, which lack sphaerotrichomes and
      have not yet been assigned to family within the suborder Dalodesmoidea. 

PMID- 26312033
TI  - Four new species of Pyropia (Bangiales, Rhodophyta) from the west coast of North
      America: the Pyropialanceolata species complex updated.
AB  - Recent molecular studies indicate that the Pyropialanceolata species complex on
      the west coast of North America is more speciose than previously thought. Based
      on extensive rbcL gene sequencing of representative specimens we recognize seven
      species in the complex, three of which are newly described: Pyropiamontereyensis
      sp. nov., Pyropiacolumbiensis sp. nov., and Pyropiaprotolanceolata sp. nov. The
      new species are all lanceolate, at least when young, and occur in the upper mid
      to high intertidal zone primarily in winter and early spring.
      Pyropiamontereyensis and Pyropiacolumbiensis are sister taxa that are distributed
      south and north of Cape Mendocino, respectively, and both occur slightly lower on
      the shore than Pyropialanceolata or Pyropiapseudolanceolata.
      Pyropiaprotolanceolata is known thus far only from Morro Rock and the Monterey
      Peninsula, California; it occurs basally to the other species in the complex in
      the molecular phylogeny. A fourth newly described species,
      Pyropiabajacaliforniensis sp. nov., is more closely related to Pyropianereocystis
      than to species in this complex proper. It is a thin species with undulate
      margins known only from Moss Landing, Monterey Bay, California, and northern Baja
      California; it also occurs in the high intertidal in spring. Porphyramumfordii, a
      high intertidal winter species that has frequently been confused with species in
      the Pyropialanceolata complex, has now been confirmed to occur from Calvert
      Island, British Columbia, to Pescadero State Park, California. 

PMID- 26312034
TI  - Bolanthusturcicus (Caryophyllaceae), a new species from Turkey.
AB  - A new species Bolanthusturcicus Koc & Hamzaoglu, sp. nov. was discovered on Hasan
      Mountain (Turkey, Aksaray province) where it grows on volcanic stony slopes and
      alpine steppe. its description, images, chorology and ecology, and threat
      category are provided in this article. It was compared with a closely related
      species, Bolanthusminuartioides (Jaub. & Spach) Hub.-Mor., Bolanthushuber
      morathii C.Simon, Bolanthusspergulifolius (Jaub. & Spach) Hub.-Mor.,
      Bolanthusfrankenioides (Boiss) Bark., Bolanthusmevlanae Aytac based on its
      general morphology and seed micromorphology. 

PMID- 26312035
TI  - Verbascumkurdistanicum (Scrophulariaceae), a new species from Hakkari, Turkey.
AB  - Verbascumkurdistanicum Firat (Scrophulariaceae), is described and illustrated as
      a new species that is located in Hakkari, Turkey. In this study, diagnostic
      morphological characters of this and closely related species (Verbascumoreophilum
      K.Koch and Verbascumpyramidatum M. Bieb) are discussed. Furthermore, distribution
      maps for the three taxa are provided. 

PMID- 26312036
TI  - Rhizophoramucronatavar.alokii - a new variety of mangrove species from the
      Andaman and Nicobar Islands, India (Rhizophoraceae).
AB  - Rhizophoramucronatavar.alokii (Rhizophoraceae), a new variety of Rhizophora from
      the Andaman and Nicobar Islands, India, is described and illustrated. The new
      variety is remarkable in having four stamens, laterally folded leaves, a short
      peduncle, thick leathery petals, and a four-sided ovary with a sessile style. A
      key for the species of Rhizophora of the Andaman and Nicobar Islands is also
      provided. 

PMID- 26312037
TI  - A revision of infrageneric classification in Astelia Banks & Sol. ex R.Br.
      (Asteliaceae).
AB  - Systematic investigations and phylogenetic analyses have indicated that Astelia,
      as currently circumscribed, is paraphyletic, with Collospermum nested within it.
      Further, AsteliasubgenusAstelia is polyphyletic, and Astelia subgenera
      Asteliopsis and Tricella are paraphyletic, as currently circumscribed. Revision
      of the subgeneric classification of Astelia is warranted to ensure classification
      accurately reflects the evolutionary history of these taxa. Collospermum is
      relegated to synonymy within Astelia. Astelia is dioecious or polygamodioecious,
      with a superior ovary, anthers dorsi- or basifixed, pistillodes or pistils that
      have a single short or poorly defined style, a 3 lobed stigma, and fleshy uni- or
      trilocular fruit with funicular hairs that are poorly to well developed.
      AsteliasubgenusCollospermum (Skottsb.) Birch is described. A key to Astelia
      sections is provided. Asteliahastata Colenso, Asteliamontana Seem., and
      Asteliamicrosperma Colenso pro parte are resurrected and the new combination
      Asteliasamoense (Skottsb.) Birch, comb. nov. is made. 

PMID- 26312038
TI  - Typification and taxonomic status re-evaluation of 15 taxon names within the
      species complex Cymbellaaffinis/tumidula/turgidula (Cymbellaceae,
      Bacillariophyta).
AB  - Specimens belonging to the Cymbellaaffinis / Cymbellatumidula / Cymbellaturgidula
      species complex have many taxonomic problems, due to their high morphological
      variability and lack of type designations. Fifteen taxon names of this complex,
      distributed in five species, were re-evaluated concerning their taxonomic status,
      and lectotypified based on original material. In addition to light microscopy,
      some material was analyzed by electron microscopy. Four new combinations are
      proposed in order to reposition infraspecific taxa. 

PMID- 26312039
TI  - A new species of Centaureasect.Pseudoseridia (Asteraceae) from north-eastern
      Turkey.
AB  - Centaureaziganensis Yuzb., M. Bona & I. Genc, a new species is described and
      illustrated from Gumushane province, NE Turkey. The new species grows in rocky
      places on the south face of Zigana Mountains, and is closely related to
      Centaureadrabifolioides, from which it differs mainly in stem, achene and
      phyllary appendage characters. Micromorphological structures of achenes and
      karyological features of Centaureaziganensis and Centaureadrabifolioides were
      examined in this study. 

PMID- 26312040
TI  - Revision of the fern genus Orthiopteris (Saccolomataceae) in Malesia and adjacent
      regions.
AB  - A taxonomic revision of the Old-World representatives of the fern genus
      Orthiopteris is presented. We recognize eight species, one of which is newly
      described (Orthiopterissamoensis), and five varieties, of which two are newly
      described (Orthiopteriscampyluravar.insularis and Orthiopteriscampyluravar.laxa).
      Orthiopterisacuminata, Orthiopteriscaudata, Orthiopterisminor and
      Orthiopteriskingii are all reduced to varieties of Orthiopteriscampylura. 

PMID- 26312041
TI  - Adiantumshastense, a new species of maidenhair fern from California.
AB  - A new species of Adiantum is described from California. This species is endemic
      to northern California and is currently known only from Shasta County. We
      describe its discovery after first being collected over a century ago and
      distinguish it from Adiantumjordanii and Adiantumcapillus-veneris. It is
      evergreen and is sometimes, but not always, associated with limestone. The range
      of Adiantumshastense Huiet & A.R.Sm., sp. nov., is similar to several other
      Shasta County endemics that occur in the mesic forests of the Eastern Klamath
      Range, close to Shasta Lake, on limestone and metasedimentary substrates. 

PMID- 26312042
TI  - Two new species of Hoya R.Br. (Apocynaceae, Asclepiadoideae) from Borneo.
AB  - Two new Hoya R.Br. species from Borneo are described and illustrated. The first,
      Hoyaruthiae Rodda was collected in Sabah on Bukit Baturong, a limestone outcrop.
      It is one of the few species in the genus to have clear exudate. It is compared
      with the morphologically related Hoyauncinata Teijsm. and Binn. The other,
      Hoyabakoensis Rodda, was collected in the kerangas forests of Bako National Park.
      It belongs to HoyasectionAcanthostemma (Bl.) Kloppenb., a section with numerous
      members in the Philippines but under-represented in Borneo. 

PMID- 26312043
TI  - Monograph of Coccinia (Cucurbitaceae).
AB  - This monograph deals with all 95 names described in the Cucurbitaceae genus
      Coccinia and recognizes 25 species. Taxonomic novelties are
      Cocciniaadoensisvar.aurantiaca (C.Jeffrey) Holstein, stat. nov.,
      Cocciniasessilifoliavar.variifolia (A.Meeuse) Holstein, stat. nov., and
      Cocciniaadoensisvar.jeffreyana Holstein, var. nov. For the 25 species 3157
      collections were examined, of which 2024 were georeferenced to produce
      distribution maps. All species are distributed in sub-Saharan Africa with one
      species, Cocciniagrandis, extending from Senegal in West Africa east to Indonesia
      and being naturalized on Pacific Islands, in Australia, the Caribbean, and South
      America. Coccinia species are dioecious creepers or climbers with simple or bifid
      tendrils that occupy a range of habitats from arid scrubland, woodlands to
      lowland rainforest and mist forest. The corolla of Coccinia species is
      sympetalous, usually pale yellow to orange, and 1 to 4.5 cm long. Pollination is
      by bees foraging for pollen or nectar. After pollination, the developing ovary
      often exhibits longitudinal mottling, which usually disappears during maturation.
      All species produce berries with a pericarp in reddish colors (orange-red through
      to scarlet red), hence the generic name. The globose to cylindrical fruits
      contain numerous grayish-beige flat to lenticular seeds. Chromosome numbers are
      2n = 20, 24, and 22 + XX/XY. Many Coccinia species are used for food, either as
      roasted tubers, greens as spinach, or the fruits as vegetables. Medicinal value
      is established in Cocciniagrandis, of which leaves and sap are used against
      diabetes. 

PMID- 26312044
TI  - A revision of Spondias L. (Anacardiaceae) in the Neotropics.
AB  - As part of an ongoing study of Anacardiaceae subfamily Spondioideae, the ten
      native and one introduced species of Spondias in the Neotropics are revised. The
      genus is circumscribed. Three new species, Spondiasadmirabilis,
      Spondiasexpeditionaria, and Spondiasglobosa, are described and illustrated; a key
      to the taxa found in the Neotropics and distribution maps are provided. The
      Paleotropical species and allied genera are reviewed. Diagnostic character sets
      include leaf architecture, habit, flower morphology, and gross fruit morphology.
      Notes on the ecology and economic botany of the species are provided. 

PMID- 26312045
TI  - Cornus*elwinortonii and Cornus*rutgersensis (Cornaceae), new names for two
      artificially produced hybrids of big-bracted dogwoods.
AB  - Big-bracted dogwoods (Cornus sp.) are well-known plants in North America and
      eastern Asia where they occur as wild, generally spring-flowering understory
      trees. They are also popular ornamental landscape plants, and many economically
      important cultivars are propagated and sold across North America, Europe, and
      Asia. Starting in the late 1960s, Elwin Orton of Rutgers University in New Jersey
      (USA) utilized three geographically disjunct species of dogwoods, Cornusflorida
      (eastern North America), Cornusnuttallii (western North America), and Cornuskousa
      (East Asia), in an extensive interspecific hybridization program. He was
      successful in developing the first-ever interspecific F1 hybrids of these
      species, several of which have become staple items in the ornamental nursery
      trade due to their enhanced ornamental qualities and resistance to diseases. The
      original F1 plants are still alive at Rutgers University. While they have been
      available for decades in horticultural commerce, the interspecific hybrid crosses
      were never formally described and their scientific hybrid names were never
      published. For the Cornuskousa * Cornusflorida hybrids, the name Cornus
      'rutgersensis' has been used on occasion in the horticultural trade, but without
      proper citation and description. Here, it is formally named Cornus*rutgersensis
      Mattera, T. Molnar, & Struwe, hybr. nov. For the Cornuskousa * Cornusnuttallii
      hybrids, no previous name has been used, and it is hereby named
      Cornus*elwinortonii Mattera, T. Molnar, & Struwe, hybr. nov. The need for
      providing scientific names for commonly used horticultural hybrids is discussed.
      Holotype material for both hybrid names was collected from the original F1
      hybrids for full documentation, typification, and description. The comparative
      intermediate development of leaves, inflorescence structures, and fruit types of
      the hybrids and their parents is discussed and illustrated. Etymology, phenology,
      and cultivation aspects of these hybrids and their cultivars including
      backcrosses to Cornuskousa are also presented. 

PMID- 26312046
TI  - Spiradiclislonganensis, a new species of Rubiaceae from China.
AB  - A new species of Spiradiclis (Rubiaceae) was found during our field trip to
      Guangxi, China, and is described here as Spiradiclislonganensis R. J. Wang. This
      species is readily distinguishable from other prostrate and decumbent species of
      the genus described previously by dense pubescence all over the plant, 5-20 small
      flowers per cymose, linear calyx lobes, and tubular corolla. The conservation
      status of VU was preliminarily assessed according to IUCN categories and
      criteria. 

PMID- 26312047
TI  - Stigmaphyllonpatricianum-firmenichianum (Malpighiaceae), a new species from
      Loyalty Islands, New Caledonia.
AB  - A new species of Stigmaphyllon (Malpighiaceae) is described:
      Stigmaphyllonpatricianum-firmenichianum Butaud. It is restricted to the coral
      islands of Ouvea, Lifou and Mare in the Loyalty Islands Province (New Caledonia)
      and is most similar to Stigmaphyllondiscolor (Gand.) C.E.Anderson, known from New
      Caledonia and Solomon Islands. Previously, plants now known as
      Stigmaphyllonpatricianum-firmenichianum were included in Stigmaphyllontaomense
      (Baker f.) C.E.Anderson, endemic to the northern part of Grande-Terre and Belep
      Islands (New Caledonia). A new circumscription of Stigmaphyllontaomense is
      proposed. The regional key for New Caledonian species of Stigmaphyllon is
      updated. 

PMID- 26312048
TI  - The Pteridaceae family diversity in Togo.
AB  - BACKGROUND: The Pteridaceae family is the largest fern family in Togo by its
      specific and generic diversity. Like all other families of ferns in the country,
      Pteridaceae are poorly studied and has no identification key. The objective of
      this study is to perform a taxonomic revision and list establishment of this
      family of leptosporangiate ferns in the light of current available knowledge
      about the family. Pteridaceae was also assessed in terms of its diversity and
      conservation status, this was conducted through the recent field data and the
      existing herbaria specimens. The current study permits to confirm the presence of
      Pteris similis Kuhn. which brought the number of Pteridaceae to 17 in Togo. NEW
      INFORMATION: This study provides first local scientific information about the
      fern flora of Togo. It confirmed the presence of Pterissimilis Kuhn. in Togo and
      brought the Pteridaceae family diversity to 17 species. A species identification
      key is provided for the easy identification of the Pteridaceae of Togo.

PMID- 26312049
TI  - Catalogue of type specimens of fungi and lichens deposited in the Herbarium of
      the University of Granada (Spain).
AB  - BACKGROUND: A catalogue of types from the Herbarium of the University of Granada
      has not previously been compiled. As a result, a search of these collections in
      order to compile digital images for preservation and publication yielded a large
      number of formerly unrecognized types. NEW INFORMATION: This dataset contains the
      specimen records from the catalogue of the nomenclature types of fungi and
      lichens in the Herbarium of the University of Granada, Spain. These herbarium
      specimens are included in the GDA and GDAC collections, acronyms from Index
      Herbariorum (Thiers 2014). At this time, the type collection of fungi and lichens
      contains 88 type specimens of 49 nominal taxa, most from Agaricales and the genus
      Cortinarius, described from the western Mediterranean, mainly Spain, by the
      following authors: V.Antonin, J.Ballara, A.Bidaud, G.F.Bills, M.Bon, C.Cano,
      M.Casares, G.Chevassut, M.Contu, F.Esteve-Raventos, R.Galan, L.Guzman-Davalos,
      R.Henry, E.Horak, R.Mahiques, G.Malencon, P.Moenne-Loccoz, G.Moreno, A.Ortega,
      F.Palazon, V.N.Suarez.-Santiago, A.Vezda, J.Vila, and M.Villareal. For each
      specimen, the locality indication, species name, observation date, collector,
      type status, related information, associated sequences, other catalogue numbers
      related to each type, and image URL are recorded. The dataset is associated with
      an image collection named "Coleccion de imagenes de los tipos nomenclaturales de
      hongos, liquenes, musgos y algas incluidos en el Herbario de la Universidad de
      Granada (GDA y GDAC)" (Vizoso and Quesada 2013) which is housed and accessible at
      the Global Biodiversity Information Facility in Spain (GBIF.ES) Hosting and
      Publishing Service "Biodiversity Image Portal of Spanish collections" and is also
      available at the Herbarium of University of Granada institutional web (Vizoso
      2014a, Vizoso 2014b). That image collection contains 113 images, of which 56
      correspond to the nomenclature types of 49 taxa (47 fungi, 2 lichens), the rest
      of the images in this collection correspond to documents and specimens or
      microscopy photographs which are included in the herbarium specimens of fungi.
      These complement and document the process of the typification.

PMID- 26312050
TI  - Displaying bias in sampling effort of data accessed from biodiversity databases
      using ignorance maps.
AB  - BACKGROUND: Open-access biodiversity databases including mainly citizen science
      data make temporally and spatially extensive species' observation data available
      to a wide range of users. Such data have limitations however, which include:
      sampling bias in favour of recorder distribution, lack of survey effort
      assessment, and lack of coverage of the distribution of all organisms. These
      limitations are not always recorded, while any technical assessment or scientific
      research based on such data should include an evaluation of the uncertainty of
      its source data and researchers should acknowledge this information in their
      analysis. The here proposed maps of ignorance are a critical and easy way to
      implement a tool to not only visually explore the quality of the data, but also
      to filter out unreliable results. NEW INFORMATION: I present simple algorithms to
      display ignorance maps as a tool to report the spatial distribution of the bias
      and lack of sampling effort across a study region. Ignorance scores are expressed
      solely based on raw data in order to rely on the fewest assumptions possible.
      Therefore there is no prediction or estimation involved. The rationale is based
      on the assumption that it is appropriate to use species groups as a surrogate for
      sampling effort because it is likely that an entire group of species observed by
      similar methods will share similar bias. Simple algorithms are then used to
      transform raw data into ignorance scores scaled 0-1 that are easily comparable
      and scalable. Because of the need to perform calculations over big datasets,
      simplicity is crucial for web-based implementations on infrastructures for
      biodiversity information. With these algorithms, any infrastructure for
      biodiversity information can offer a quality report of the observations accessed
      through them. Users can specify a reference taxonomic group and a time frame
      according to the research question. The potential of this tool lies in the
      simplicity of its algorithms and in the lack of assumptions made about the bias
      distribution, giving the user the freedom to tailor analyses to their specific
      needs.

PMID- 26312051
TI  - Preliminary data on pupal development, lifespan and fertility of Cynomyamortuorum
      (L., 1761) in Belgium (Diptera: Calliphoridae).
AB  - BACKGROUND: The calliphorid Cynomyamortuorum (L., 1761) is a species of forensic
      interest, present mainly in the Palaearctic Region. Nearly nothing is known about
      its life history. NEW INFORMATION: We provide here the first data regarding pupal
      weight evolution during the pupal stage, female fertility and life expectancy of
      the species. At 22 degrees C under a variable regime of temperatures, the egg-to
      adult development time was an average of 18.05 +/- 0.72 and 18.47 +/- 0.67 days
      for females and males, respectively, in the control group. The pupal stage
      represented 56.7% of the total development. The development time from egg to
      adult and the duration of the pupal stage were significantly longer for males
      than for females. The measurement of pupal weight at the start of the pupal
      period revealed that female pupae were significantly lighter than male pupae by
      nearly 20%. This difference between the sexes was also observed for the dry
      weight of adults. An average decrease of 8.75% was observed throughout the first
      8 days of the pupal stage, after which most adults started to emerge. The tested
      females produced an average of 176.13 +/- 66.62 eggs throughout the egg-laying
      period. The average lifespan after emergence was 12.10 +/- 4.09 days for females
      and 12.60 +/- 2.95 days for males, with a median of 12.50 days for both sexes.

PMID- 26312052
TI  - Biodiversity assessment among two Nebraska prairies: a comparison between
      traditional and phylogenetic diversity indices.
AB  - BACKGROUND: Conservation of the evolutionary diversity among organisms should be
      included in the selection of priority regions for preservation of Earth's
      biodiversity. Traditionally, biodiversity has been determined from an assessment
      of species richness (S), abundance, evenness, rarity, etc. of organisms but not
      from variation in species' evolutionary histories. Phylogenetic diversity (PD)
      measures evolutionary differences between taxa in a community and is gaining
      acceptance as a biodiversity assessment tool. However, with the increase in the
      number of ways to calculate PD, end-users and decision-makers are left wondering
      how metrics compare and what data are needed to calculate various metrics. NEW
      INFORMATION: In this study, we used massively parallel sequencing to generate
      over 65,000 DNA characters from three cellular compartments for over 60 species
      in the asterid clade of flowering plants. We estimated asterid phylogenies from
      character datasets of varying nucleotide quantities, and then assessed the effect
      of varying character datasets on resulting PD metric values. We also compared
      multiple PD metrics with traditional diversity indices (including S) among two
      endangered grassland prairies in Nebraska (U.S.A.). Our results revealed that PD
      metrics varied based on the quantity of genes used to infer the phylogenies;
      therefore, when comparing PD metrics between sites, it is vital to use comparable
      datasets. Additionally, various PD metrics and traditional diversity indices
      characterize biodiversity differently and should be chosen depending on the
      research question. Our study provides empirical results that reveal the value of
      measuring PD when considering sites for conservation, and it highlights the
      usefulness of using PD metrics in combination with other diversity indices when
      studying community assembly and ecosystem functioning. Ours is just one example
      of the types of investigations that need to be conducted across the tree of life
      and across varying ecosystems in order to build a database of phylogenetic
      diversity assessments that lead to a pool of results upon which a guide through
      the plethora of PD metrics may be prepared for use by ecologists and conservation
      planners.

PMID- 26312053
TI  - Tree Diversity and Dynamics of the Forest of Seu Nico, Vicosa, Minas Gerais,
      Brazil.
AB  - BACKGROUND: To understand future changes in community composition due to global
      changes, the knowledge about forest community dynamics is of crucial importance.
      To improve our understanding about processes and patterns involved in maintaining
      species rich Neotropical ecosystems, we provide here a dataset from the one
      hectare Forest of Seu Nico (FSN) Dynamics Plot from Southeastern Brazil. NEW
      INFORMATION: We report diameter at breast height, basal area and height
      measurements of 2868 trees and treelets identified from two census spanning over
      a nine-year period. Furthermore, soil properties and understory light
      availability of all 100 10 x 10m subplots from the one hectare FSN Dynamics Plot
      during the second census are given.

PMID- 26312054
TI  - A Preliminary Investigation of Reversing RML: From an RDF dataset to its Column
      Based data source.
AB  - BACKGROUND: A large percentage of scientific data with tabular structure are
      published on the Web of Data as interlinked RDF datasets. When we come to the
      issue of long-term preservation of such RDF-based digital objects, it is
      important to provide full support for reusing them in the future. In particular,
      it should include means for both players who have no familiarity with RDF data
      model and, at the same time, who by working only with the native format of the
      data still provide sufficient information. To achieve this, we need mechanisms to
      bring the data back to their original format and structure. NEW INFORMATION: In
      this paper, we investigate how to perform the reverse process for column-based
      data sources. In particular, we devise an algorithm, RML2CSV, and exemplify its
      implementation in transforming an RDF dataset into its CSV tabular structure,
      through the use of the same RML mapping document that was used to generate the
      set of RDF triples. Through a set of content-based criteria, we attempt a
      comparative evaluation to measure the similarity between the rebuilt CSV and the
      original one. The results are promising and show that, under certain assumptions,
      RML2CSV reconstructs the same data with the same structure, offering more
      advanced digital preservation services.

PMID- 26312055
TI  - Melampyrumsylvaticum as a pre-diapause host plant of the scarce fritillary
      (Euphydryasmaturna) in Finland.
AB  - BACKGROUND: The scarce fritillary Euphydryas (Hypodryas) maturna (L.) is included
      in the Habitats Directive's Annexes II and IV(a). Therefore, it is crucially
      important to be able to define the habitat and breeding places of E.maturna in a
      correct and unbiased way. NEW INFORMATION: Data on a previously unknown pre
      diapause main host plant, the small cow-wheat (Melampyrumsylvaticum L.), of
      Euphydryasmaturna in Finland is presented.

PMID- 26312057
TI  - Mental Rotation of Dynamic, Three-Dimensional Stimuli by 3-Month-Old Infants.
AB  - Mental rotation involves transforming a mental image of an object so as to
      accurately predict how the object would look if it were rotated in space. This
      study examined mental rotation in male and female 3-month-olds, using the stimuli
      and paradigm developed by Moore & Johnson (2008). Infants were habituated to a
      video of a 3-dimensional object rotating back and forth through a 240 degrees 
      angle around the vertical axis. After habituation, infants were tested both with
      videos of the same object rotating through the previously unseen 120 degrees 
      angle, and with the mirror image of that display. Unlike females, who fixated the
      test displays for approximately equal durations, males spent significantly more
      time fixating the familiar object than the mirror-image object. Because
      familiarity preferences like this emerge when infants are relatively slow to
      process a habituation stimulus, the data support the interpretation that mental
      rotation of dynamic 3-dimensional stimuli is relatively difficult-but possible
      for 3-month-old males. Interpretation of the sex differences observed in 3- and 5
      month-olds' performances is discussed.

PMID- 26312056
TI  - Proteomic analysis of quail calcified eggshell matrix: a comparison to chicken
      and turkey eggshell proteomes.
AB  - BACKGROUND: Eggshell mineralization in commercially important species such as
      chicken, turkey or quail is of interest as a general model of calcium carbonate
      biomineralization. Knowledge of proteins and molecular mechanisms in eggshell
      assembly may also pave the way to manipulation of thickness of the calcified
      layer or other features. Comparison of eggshell matrix proteomes of different
      species may contribute to a better understanding of the mineralization process.
      The recent publication of the quail genome sequence now enables the proteomic
      analysis of the quail shell matrix and this comparison with those of chicken and
      turkey. RESULTS: The quail eggshell proteome comprised 622 identified proteins,
      311 of which were shared with chicken and turkey eggshell proteomes. Forty-eight
      major proteins (iBAQ-derived abundance higher than 0.1 % of total identified
      proteome) together covered 94 % of total proteome mass. Fifteen of these are also
      among the most abundant proteins in chicken and turkey eggshell matrix. Only
      three proteins with a percentage higher than 1.0 % of the total had not
      previously been identified as eggshell matrix proteins. These were an
      uncharacterized member of the latexin family, an uncharacterized protease
      inhibitor containing a Kunitz domain, and gastric intrinsic factor. The most
      abundant proteins were ovocleidin-116, ovalbumin and ovocalyxin-36 representing
      approximately 31, 13 and 8 % of the total identified proteome, respectively. The
      major phosphoproteins were ovocleidin-116 and osteopontin. While osteopontin
      phosphorylation sites were predominantly conserved between chicken and quail
      sequences, conservation was less in ovocleidin-116. CONCLUSIONS: Ovocleidin-116
      and ovocalyxin-36 are among the most abundant eggshell matrix proteins in all
      three species of the family Phasianidae analyzed so far, indicating that their
      presently unknown function is essential for eggshell mineralization. Evidence for
      other chicken eggshell-specific proteins in quail was inconclusive. Therefore
      measurement of additional eggshell proteomes, especially from species of
      different families and preferentially from outside the order Galliformes, will be
      necessary.

PMID- 26312058
TI  - Towards implementing coordinated healthy lifestyle promotion in primary care: a
      mixed method study.
AB  - BACKGROUND: Primary care is increasingly being encouraged to integrate healthy
      lifestyle promotion in routine care. However, implementation has been suboptimal.
      Coordinated care could facilitate lifestyle promotion practice but more empirical
      knowledge is needed about the implementation process of coordinated care
      initiatives. This study aimed to evaluate the implementation of a coordinated
      healthy lifestyle promotion initiative in a primary care setting. METHODS: A
      mixed method, convergent, parallel design was used. Three primary care centres
      took part in a two-year research project. Data collection methods included
      individual interviews, document data and questionnaires. The General Theory of
      Implementation was used as a framework in the analysis to integrate the data
      sources. RESULTS: Multi-disciplinary teams were implemented in the centres
      although the role of the teams as a resource for coordinated lifestyle promotion
      was not fully embedded at the centres. Embedding of the teams was challenged by
      differences among the staff, patients and team members on resources, commitment,
      social norms and roles. CONCLUSIONS: The study highlights the importance of
      identifying and engaging key stakeholders early in an implementation process. The
      findings showed how the development phase influenced the implementation and
      embedding processes, which add aspects to the General Theory of Implementation.

PMID- 26312059
TI  - Integrating rheumatology care in the community: can shared care work?
AB  - INTRODUCTION: Singapore's rapidly ageing population and chronic disease burden at
      public hospital specialist clinics herald a silver tsunami. In Singapore, "right
      siting" aims to manage stable chronic disease in primary care at a lower cost. To
      improve the quality of rheumatology care, we created shared care between
      rheumatologist and family physician to reduce hospital visits. METHODS: Clinical
      practice improvement methodology was used to structure shared care of stable
      patients between hospital rheumatologists and eleven community family physicians;
      one ran a hospital clinic. A case manager coordinated the workflow. RESULTS:
      About 220 patients entered shared care over 29 months. Patients without hospital
      subsidies (private patients) and private family physicians independently
      predicted successful shared care, defined as one cycle of alternating care.
      DISCUSSION: Our shared care model incorporated a case manager, systematic
      workflows, patient selection criteria, willing family physician partners and
      rheumatologists in the absence of organizational integration. Health care
      affordability impacts successful shared care. Government subsidy hindered right
      siting to private primary care. CONCLUSIONS: Financing systems in Singapore, at
      health policy level, must allow transfer of hospital subsidies to primary care,
      both private and public, to make it more affordable than hospital care.
      Structural integration will create a seamless continuum between hospital and
      primary care.

PMID- 26312060
TI  - Matrix-Bound VEGF Mimetic Peptides: Design and Endothelial Cell Activation in
      Collagen Scaffolds.
AB  - Long term survival and success of artificial tissue constructs depend greatly on
      vascularization. Endothelial cell (EC) differentiation and vasculature formation
      are dependent on spatio-temporal cues in the extracellular matrix that
      dynamically interact with cells, a process difficult to reproduce in artificial
      systems. Here we present a novel bifunctional peptide that mimics matrix-bound
      vascular endothelial growth factor (VEGF) and can be used to encode spatially
      controlled angiogenic signals in collagen scaffolds. The peptide is comprised of
      a collagen mimetic domain that was previously reported to bind to type I collagen
      by a unique hybridization mechanism, and a VEGF mimetic domain with pro
      angiogenic activity. Circular dichroism and collagen binding studies confirm the
      triple helical structure and the collagen binding affinity of the collagen
      mimetic domain, and EC culture studies demonstrate the peptide's ability to
      induce endothelial cell morphogenesis and network formation as a matrix-bound
      factor in 2D and 3D collagen scaffolds. We also show spatial modification of
      collagen substrates with this peptide that allows localized EC activation and
      network formation. These results demonstrate that the peptide can be used to
      present spatially directed angiogenic cues in collagen scaffolds, which may be
      useful for engineering organized microvasculature.

PMID- 26312061
TI  - An overview of regional and local characteristics of aerosols in South Africa
      using satellite, ground, and modeling data.
AB  - We present a comprehensive overview of particulate air quality across the five
      major metropolitan areas of South Africa (Cape Town, Bloemfontein, Johannesburg
      and Tshwane (Gauteng Province), the Industrial Highveld Air Quality Priority Area
      (HVAPA), and Durban), based on a decadal (1 January 2000 to 31 December 2009)
      aerosol climatology from multiple satellite platforms and detailed analysis of
      ground-based data from 19 sites throughout Gauteng Province. Satellite analysis
      was based on aerosol optical depth (AOD) from MODIS Aqua and Terra (550 nm) and
      MISR (555 nm) platforms, Angstrom Exponent (alpha) from MODIS Aqua (550/865 nm)
      and Terra (470/660 nm), ultraviolet aerosol index (UVAI) from TOMS, and results
      from the Goddard Ozone Chemistry Aerosol Radiation and Transport (GOCART) model.
      At continentally influenced sites, AOD, alpha, and UVAI reach maxima (0.12-0.20,
      1.0-1.8, and 1.0-1.2, respectively) during austral spring (September-October),
      coinciding with a period of enhanced dust generation and the maximum integrated
      intensity of close-proximity and subtropical fires identified by MODIS Fire
      Information for Resource Management System (FIRMS). Minima in AOD, alpha, and
      UVAI occur during winter. Results from ground monitoring indicate that low-income
      township sites experience by far the worst particulate air quality in South
      Africa, with seasonally averaged PM10 concentrations as much as 136 % higher in
      townships that in industrial areas. We report poor agreement between satellite
      and ground aerosol measurements, with maximum surface aerosol concentrations
      coinciding with minima in AOD, alpha, and UVAI. This result suggests that
      remotely sensed data are not an appropriate surrogate for ground air quality in
      metropolitan South Africa.

PMID- 26312062
TI  - Serum Cytokeratin-18 Levels for Liver Fibrosis Prediction.

PMID- 26312063
TI  - Serum cytokine profiling analysis for zheng differentiation in chronic hepatitis
      B.
AB  - BACKGROUND: Liver-gallbladder dampness-heat (LGDH) and liver kidney yin
      deficiency (LKYD) syndromes are Chinese medicine (CM) zhengs in chronic hepatitis
      B (CHB) patients. This study aims to investigate the changes in cytokines and
      their profiles accompanied by different biological responses in LGDH and LKYD in
      CHB. METHODS: During 2010-2012, a total of 138 morning fasting venous blood
      samples were obtained from participants in Shuguang Hospital, Shanghai University
      of Traditional Chinese Medicine in Shanghai, China. First, serum samples from 20
      health controls (HCs) and 40 CHB patients (20 LGDH, 20 LKYD) were collected to
      detect the profiles of cytokines by multiplex biometric ELISA-based immunoassay.
      Random forest (RF) with a fivefold cross-validation was used to analyze the
      significant cytokines. Then the significant cytokines were validated using serum
      samples from an independent cohort of 60 CHB patients (30 LGDH, 30 LKYD) and 18
      HCs. RESULTS: There were different profiles of cytokines in LGDH and LKYD. Twenty
      three significantly differentially expressed cytokines were detected, among which
      three cytokines, interleukin (IL)-17, macrophage inflammatory protein (MIP)
      1alpha, and MIP-1beta, with the largest Gini scores were identified by RF, and
      further evaluated for their significant changes in serum levels. A receiver
      operator characteristic analysis revealed that the logistic regression panel
      could differentiate LGDH from LKYD (P < 0.001; AUC = 0.827). A functional pathway
      analysis showed that cytokine-cytokine receptor interaction, cytosolic DNA
      sensing pathway, and chemokine signaling pathway overlapped between LGDH and
      LKYD, whereas Toll-like receptor signaling pathway, intestinal immune network for
      IgA production, NOD-like receptor signaling pathway, and Jak-STAT signaling
      pathway were only enriched in LGDH. CONCLUSIONS: There were characteristic
      cytokines profiles in LGDH and LKYD with different inflammatory and immune
      responses. IL-17, MIP-1alpha, and MIP-1beta might be involved in the
      differentiation of LGDH and LKYD in CHB.

PMID- 26312064
TI  - Social Communication Effects of Peer-Mediated Recess Intervention for Children
      with Autism.
AB  - Children with ASD face enormous challenges in the area of social functioning.
      Research has shown that impairments in social functioning distinguish this
      population from both typically developing children and children with
      disabilities. This study incorporated several evidence-based social skills
      teaching procedures (i.e., direct instruction, priming, prompting, peer
      mediation, contingent reinforcement, and token economies) directly in the recess
      setting to increase appropriate social behaviors for four children with ASD (ages
      6-8). Elements of Peer Networks and Pivotal Response Training (two types of
      social skills intervention packages in the literature) were included. Results
      showed significant increases in social communication between focus children and
      their peers, as well as generalization of skills to non-intervention recesses.

PMID- 26312065
TI  - Microalgal lipid production using the hydrolysates of rice straw pretreated with
      gamma irradiation and alkali solution.
AB  - BACKGROUND: Lignocellulosic biomass has long been recognized as a potential
      sustainable source of sugars for biofuels. However, many physicochemical
      structural and compositional factors inhibit the enzymatic digestibility of the
      lignocellulosic biomass. In this study, efficient pretreatment method of rice
      straw (RS) was developed and the RS hydrolysate was applied in the cultivation of
      microalgae for lipid production. RESULTS: Gamma ray irradiation (GRI) and alkali
      solution were used for the pretreatment, and saccharification was carried out
      with lignocellulolytic enzymes. When RS was pretreated by combined GRI and alkali
      method, the glucose and xylose saccharification yield after enzymatic hydrolysis
      increased up to 91.65 and 98.84 %, respectively. The enzymatic hydrolysate from
      the RS pretreated with the combined method was used to cultivate Chlorella
      protothecoides for lipid production. The maximum concentrations of biomass and
      fatty acid methyl ester of cells were 6.51 and 2.95 g/L, respectively. The lipid
      content of C. protothecoides from RS hydrolysate was comparable to that from
      glucose, and the lipid composition was similar between different carbon sources.
      CONCLUSION: These results demonstrate that the combined pretreatment with gamma
      irradiation was highly effective in preparing hydrolysate, and the rice straw
      hydrolysate could be used as an alternative carbon source for microalgal lipid
      production for biofuel.

PMID- 26312067
TI  - Functional relationship of furfural yields and the hemicellulose-derived sugars
      in the hydrolysates from corncob by microwave-assisted hydrothermal pretreatment.
AB  - BACKGROUND: Corncob as one of the most suitable feedstock for the production of a
      variety of high-value-added chemicals is receiving increasing attention worldwide
      because of the characteristics of high carbohydrate (cellulose and
      hemicelluloses) contents and high energy densities. Furfural produced from
      hemicelluloses is a highly versatile and key feedstock used in the manufacture of
      a wide range of biofuel and important chemicals in different fields. Achieving
      high furfural yields from corncob combining green approaches and efficient
      equipment has the promising potential for biomass-to-biofuel technologies. To
      understand the dissolving mechanism of corncob sugars and reveal the relationship
      between the hydrolysate composition and furfural yields, a two-step approach was
      proposed using microwave-assisted hydrothermal pretreatment and subsequently
      heterogeneous catalytic process. RESULTS: Released hemicelluloses in the first
      stage were mainly in forms of monosaccharide, oligosaccharides, and water-soluble
      polysaccharide. Hydrolysates with the maximum xylose content (99.94 mg g(-1), 160
      degrees C, 90 min), the maximum xylobiose content (20.89 mg g(-1), 180  degrees
      C, 15 min), and the maximum total xylose content in monosaccharide and
      oligosaccharides (DP <= 6) (272.06 mg g(-1), 160  degrees C, 60 min) were further
      converted to furfural using tin-loaded montmorillonite as the catalyst in a
      biphasic system. The highest furfural yield (57.80 %) was obtained at 190 
      degrees C for 10 min from hydrolysates with the maximum xylose content. Moreover,
      controlled experiments showed that furfural yields from corncob hydrolysates were
      higher than those from the pure xylose solutions, and lower initial xylose
      concentration may be in favor of the furfural production. CONCLUSIONS: This work
      provides an efficient approach to produce furfural by a two-step process for the
      biomass-to-biofuel industry. Results indicated that the production of furfural
      from biomass raw materials can be controlled by the depolymerization degree of
      hemicelluloses.

PMID- 26312066
TI  - In situ micro-spectroscopic investigation of lignin in poplar cell walls
      pretreated by maleic acid.
AB  - BACKGROUND: In higher plant cells, lignin provides necessary physical support for
      plant growth and resistance to attack by microorganisms. For the same reason,
      lignin is considered to be a major impediment to the process of deconstructing
      biomass to simple sugars by hydrolytic enzymes. The in situ variation of lignin
      in plant cell walls is important for better understanding of the roles lignin
      play in biomass recalcitrance. RESULTS: A micro-spectroscopic approach combining
      stimulated Raman scattering microscopy and fluorescence lifetime imaging
      microscopy was employed to probe the physiochemical structure of lignin in poplar
      tracheid cell walls. Two forms of lignins were identified: loosely packed lignin,
      which had a long (4 ns) fluorescence lifetime and existed primarily in the
      secondary wall layers; and dense lignin, which had a short (0.5-1 ns)
      fluorescence lifetime and was present in all wall layers, including the cell
      corners, compound middle lamellae, and secondary wall. At low maleic acid
      concentration (0.025 and 0.05 M) pretreatment conditions, some of the dense
      lignin was modified to become more loosely packed. High acid concentration
      removed both dense and loosely packed lignins. These modified lignins reformed to
      make lignin-carbohydrate complex droplets containing either dense or loosely
      packed lignin (mostly from secondary walls) and were commonly observed on the
      cell wall surface. CONCLUSIONS: We have identified dense and loosely packed
      lignins in plant cell walls. During maleic acid pretreatment, both dense lignin
      droplets and loosely packed lignin droplets were formed. Maleic acid pretreatment
      more effectively removes loosely packed lignin in secondary walls which increases
      enzyme accessibility for digestion.

PMID- 26312068
TI  - Down-regulation of p-coumaroyl quinate/shikimate 3'-hydroxylase (C3'H) and
      cinnamate 4-hydroxylase (C4H) genes in the lignin biosynthetic pathway of
      Eucalyptus urophylla * E. grandis leads to improved sugar release.
AB  - BACKGROUND: Lignocellulosic materials provide an attractive replacement for food
      based crops used to produce ethanol. Understanding the interactions within the
      cell wall is vital to overcome the highly recalcitrant nature of biomass. One
      factor imparting plant cell wall recalcitrance is lignin, which can be
      manipulated by making changes in the lignin biosynthetic pathway. In this study,
      eucalyptus down-regulated in expression of cinnamate 4-hydroxylase (C4H, EC
      1.14.13.11) or p-coumaroyl quinate/shikimate 3'-hydroxylase (C3'H, EC 1.14.13.36)
      were evaluated for cell wall composition and reduced recalcitrance. RESULTS:
      Eucalyptus trees with down-regulated C4H or C3'H expression displayed lowered
      overall lignin content. The control samples had an average of 29.6 %, the C3'H
      reduced lines had an average of 21.7 %, and the C4H reduced lines had an average
      of 18.9 % lignin from wet chemical analysis. The C3'H and C4H down-regulated
      lines had different lignin compositions with average S/G/H ratios of
      48.5/33.2/18.3 for the C3'H reduced lines and 59.0/39.8/1.2 for the C4H reduced
      lines, compared to the control with 65.9/33.2/1.0. Both the C4H and C3'H down
      regulated lines had reduced recalcitrance as indicated by increased sugar release
      as determined using enzymatic conversion assays utilizing both no pretreatment
      and a hot water pretreatment. CONCLUSIONS: Lowering lignin content rather than
      altering sinapyl alcohol/coniferyl alcohol/4-coumaryl alcohol ratios was found to
      have the largest impact on reducing recalcitrance of the transgenic eucalyptus
      variants. The development of lower recalcitrance trees opens up the possibility
      of using alternative pretreatment strategies in biomass conversion processes that
      can reduce processing costs.

PMID- 26312069
TI  - Metabolic engineering of Bacillus subtilis for redistributing the carbon flux to
      2,3-butanediol by manipulating NADH levels.
AB  - BACKGROUND: Acetoin reductase (Acr) catalyzes the conversion of acetoin to 2,3
      butanediol (2,3-BD) with concomitant oxidation of NADH to NAD(+). Therefore,
      intracellular 2,3-BD production is likely governed by the quantities of rate
      limiting factor(s) Acr and/or NADH. Previously, we showed that a high level of
      Acr was beneficial for 2,3-BD accumulation. RESULTS: Metabolic engineering
      strategies were proposed to redistribute carbon flux to 2,3-BD by manipulating
      NADH levels. The disruption of NADH oxidase (YodC, encoded by yodC) by insertion
      of a formate dehydrogenase gene in Bacillus subtilis was more efficient for
      enhancing 2,3-BD production and decreasing acetoin formation than the disruption
      of YodC by the insertion of a Cat expression cassette. This was because the
      former resulted in the recombinant strain AFY in which an extra NADH regeneration
      system was introduced and NADH oxidase was disrupted simultaneously. On
      fermentation by strain AFY, the highest 2,3-BD concentration increased by 19.9 %
      while the acetoin titer decreased by 71.9 %, relative to the parental strain.
      However, the concentration of lactate, the main byproduct, increased by 47.2 %.
      To further improve carbon flux and NADH to 2,3-BD, the pathway to lactate was
      blocked using the insertional mutation technique to disrupt the lactate
      dehydrogenase gene ldhA. The resultant engineered strain B. subtilis AFYL could
      efficiently convert glucose into 2,3-BD with little acetoin and lactate
      accumulation. CONCLUSIONS: Through increasing the availability of NADH and
      decreasing the concentration of unwanted byproducts, this work demonstrates an
      important strategy in the metabolic engineering of 2,3-BD production by
      integrative recombinant hosts.

PMID- 26312070
TI  - Twelve-week randomized study to compare the effect of vildagliptin vs.
      glibenclamide both added-on to metformin on endothelium function in patients with
      type 2 diabetes and hypertension.
AB  - BACKGROUND: Vildagliptin, a DPP-4 inhibitor widely used for the treatment of type
      2 diabetes mellitus (T2DM), shows beneficial effects on endothelial function.
      This study aims to evaluate the effect of vildagliptin on endothelial function
      and arterial stiffness in patients with T2DM and hypertension. METHODS: Fifty
      over 35-year-old patients with T2DM and hypertension, without cardiovascular
      disease, will be randomly allocated to two groups: group 1 will receive
      vildagliptin added-on to metformin and group 2, glibenclamide added-on to
      metformin. Biochemical tests (glycemia, glycated hemoglobin, total cholesterol,
      high-density lipoprotein cholesterol, triglycerides, creatinine, alanine
      aminotransferase, ultrasensitive C-reactive protein, and microalbuminuria), 24-h
      non-invasive ambulatory blood pressure monitoring, and assessment of endothelial
      function and arterial stiffness will be performed in both groups before and after
      12 weeks of treatment. The endothelial function will be assessed by peripheral
      arterial tonometry, which measures the reactive hyperemia index (vasodilation),
      and arterial stiffness will be evaluated by applanation tonometry. All analysis
      will be performed using SPSS Statistical Software. For all analysis, a 2-sided P
      < 0.05 will be considered statistically significant. RESULTS: The study started
      in December 2013 and patient recruitment is programed until October 2015. The
      expected results are that vildagliptin will improve the endothelial function in
      patients with T2DM and hypertension compared to glibenclamide treatment,
      independently of glycemic control. CONCLUSIONS: It is expected that this DPP-4
      inhibitor will improve endothelial function in patients with T2 DM. TRIAL
      REGISTRATION: Clinical Trials NCT02145611, registered on 11 Jun 2013.

PMID- 26312072
TI  - Numerical Simulation and Clinical Verification of the Minimally Invasive Repair
      of Pectus Excavatum.
AB  - OBJECTIVE: In this article we proposed a modeling method by building an assembled
      model to simulate the orthopedic process of minimally invasive surgery for pectus
      excavatum and got the clinical verification, which aims to provide some
      references for clinic diagnoses, treatment, and surgery planning. METHODS: The
      anterior chest model of a 15-year-old patient was built based on his CT images;
      and his finite element model and the Nuss bar were created. Coupling of nodal
      displacement was used to connect bones with cartilages of the anterior chest.
      Turning the Nuss bar over is completed by rotating displacement of it. By
      comparing the numerical simulation outcomes with clinical surgery results, the
      numerical simulation results were verified. RESULTS: The orthopedic process of
      minimally invasive surgery of pectus excavatum was simulated by model
      construction and numerical analysis. The stress, displacement fields and
      distribution of the contact pressure between the Nuss bar and costal cartilages
      were analyzed. The relationship between correcting force and displacement was
      obtained. Compared with the of clinical results, the numerical simulation results
      were close to that of the actual clinical surgery in displacement field, and the
      final contact position of the Nuss bar and the costal cartilages. CONCLUSION:
      Compared with the rigid model, the assembled simulation model is in more
      conformity with the actual clinical practice. The larger curvature results in the
      maximum equivalent stress, which is the main reason for clinical pain. Soft
      tissues and muscles should be taken into account in the numerical simulation
      process.

PMID- 26312071
TI  - Increased expression of the interleukin-1 receptor-associated kinase (IRAK)-1 is
      associated with adipose tissue inflammatory state in obesity.
AB  - BACKGROUND: The emerging role of TLR2/4 as immuno-metabolic receptors points to
      key involvement of TLR/IL-1R/MyD88 pathway in obesity/type-2 diabetes (T2D). IL1R
      associated kinase (IRAK)-1 is a critical adapter protein (serine/threonine
      kinase) of this signaling pathway. The changes in adipose tissue expression of
      IRAK-1 in obesity/T2D remain unclear. We determined modulations in IRAK-1
      gene/protein expression in the subcutaneous adipose tissues from lean, overweight
      and obese individuals with or without T2D. METHODS: A total of 49 non-diabetic
      (22 obese, 19 overweight and 8 lean) and 42 T2D (31 obese, 9 overweight and 2
      lean) adipose tissue samples were obtained by abdominal subcutaneous fat pad
      biopsy and IRAK-1 expression was determined using real-time RT-PCR,
      immunohistochemistry, and confocal microscopy. IRAK-1 mRNA expression was
      compared with adipose tissue proinflammatory mediators (TNF-alpha, IL-6, IL-18),
      macrophage markers (CD68, CD11c, CD163), and plasma markers (CCL-5, C-reactive
      protein, adiponectin, and triglycerides). The data were analyzed using t test,
      Pearson's correlation, and multiple stepwise linear regression test. RESULTS: In
      non-diabetics, IRAK-1 gene expression was elevated in obese (P = 0.01) and
      overweight (P = 0.04) as compared with lean individuals and this increase
      correlated with body mass index (r = 0.45; P = 0.001) and fat percentage (r =
      0.36; P = 0.01). In diabetics, IRAK-1 mRNA expression was also higher in obese as
      compared with lean subjects (P = 0.012). As also shown by
      immunohistochemistry/confocal microscopy in non-diabetics and by
      immunohistochemistry in diabetics, IRAK-1 protein expression was higher in obese
      than overweight and lean adipose tissues. IRAK-1 gene expression correlated
      positively/significantly with mRNAs of TNF-alpha (r = 0.46; P = 0.0008), IL-6 (r
      = 0.30; P = 0.03) and IL-18 (r = 0.31; P = 0.028) in non-diabetics; and only with
      TNF-alpha (r = 0.32; P = 0.03) in diabetics. IRAK-1 expression also correlated
      positively/significantly with CD68 (r = 0.32; P = 0.02), CD11c (r = 0.30; P =
      0.03), and CD163 (r = 0.43; P = 0.001) in non-diabetics; and only with CD163 (r =
      0.34; P = 0.02) in diabetics. IRAK-1 mRNA levels also correlated with plasma
      markers including CCL-5 (r = 0.39; P = 0.02), C-reactive protein (r = 0.48; P =
      0.005), adiponectin (r = -0.36; P = 0.04), and triglycerides (r = 0.40; P = 0.02)
      in non-diabetics; and only with triglycerides (r = -0.36; P = 0.04) in diabetics.
      IRAK-1 expression related with TLR2 (r = 0.39; P = 0.007) and MyD88 (r = 0.36; P
      = 0.01) in non-diabetics; and MyD88 (r = 0.52; P = 0.0003) in diabetics.
      CONCLUSIONS: The elevated IRAK-1 expression in obese adipose tissue showed
      consensus with local/circulatory inflammatory signatures and represented as a
      tissue marker for metabolic inflammation. The data have clinical significance as
      interventions causing IRAK-1 suppression may alleviate meta-inflammation in
      obesity/T2D.

PMID- 26312073
TI  - Optimization of Extraction Process for Polysaccharide in Salvia Miltiorrhiza
      Bunge Using Response Surface Methodology.
AB  - This study was aimed to optimize the extraction process for Salvia miltiorrhiza
      Bunge polysaccharide using response surface methodology The results showed that
      four operating parameters including microwave power, microwave time and the
      particle size had notable effects on the polysaccharide extraction of Salvia
      miltiorrhiza Bunge. The effects could be ranked in decreasing order of importance
      as follows:. Microwave power > microwave time > the comminution degree. The
      optimal extraction parameters were determined as 573.83W of Microwave power and
      8.4min of microwave time and 67.51mesh of the comminution degree, resulting in
      the yield of Salvia miltiorrhiza Bunge polysaccharide of 101.161mg / g. The
      established regression model describing polysaccharide extraction from as a
      function of the three extraction parameters was highly significant (R 2 =
      0.9953). The predicted and experimental results were found to be in good
      agreement. Thus, the model can be applicable for the prediction of polysaccharide
      extraction from Salvia miltiorrhiza Bunge. 

PMID- 26312074
TI  - Imaging of Conductivity Changes of Excitable Tissues Based on Focused Passive
      Microwave.
AB  - AIMS: Modeling of ionic distribution fluctuations of excitable tissues based on
      data elicited using focused microwave radiometry. METHODOLOGY: Focused Microwave
      Radiometry implemented to carry out measurements of in depth body temperature
      distributions, may provide the capability of sensing local electrical
      conductivity fluctuations during the cycle of actions potentials in the case of
      brain excitable cell clusters. An analog beamformer consisting of a conductive
      inner-surface ellipsoidal cavity is used to focus the chaotic-black body
      radiation emerging from human tissues by providing convergence of the
      electromagnetic energy from one focus area where the phantom or subject is
      placed, to the other where the antennas of sensitive radiometric receivers are
      positioned. During the past 10 years numerous phantom, animal and human volunteer
      experiments have been performed with the focused radiometry imaging system. The
      results show that the detected changes of the output radiometric voltage are
      attributed to temperature and/or conductivity changes that occur locally
      concentrated at the areas of interest under measurement. Theoretical and
      experimental studies are continuously carried out at various frequency bands in
      conjunction with the use of matching materials placed around the human head or
      phantom to improve focusing and detection depth. It seems that the manipulation
      of the focusing area in the tissue in terms of detection depth and spatial
      resolution is feasible depending on the suitable combination of operation
      frequencies and matching material. In this paper, theoretical analysis of ion
      charge diffusion during the cycle of action potentials, propagating along the
      axons in case of measurements of specific cortical regions is presented. The ion
      charge diffusion modeling is based on electromagnetic diffusion analogies in the
      effort to explain the observed experimental results obtained under various
      psychophysiological conditions in the case of human volunteer measurements.
      RESULTS: By implementing an analysis based on the continuity equations of ionic
      charges it is concluded that the microwave radiometry output voltage is not
      affected by the temporal and spatial average fluctuations of Na(+), K(+), and Cl(
      ) ions of neural cell axons. CONCLUSION: The analysis of conductivity
      fluctuations in the central neural system in conjunction with the electromagnetic
      analysis of the system, leads to the interpretation of the previously acquired
      experimental data. The application of this technique with other brain functional
      mapping methods, may provide complementary knowledge to the understanding of the
      functional organization of psychophysiological processes.

PMID- 26312075
TI  - The Effect of Lightly Gripping a Cane on the Dynamic Balance Control.
AB  - The purpose of the current study was to investigate the effect of lightly
      gripping a cane on the Functional Reach Test (FRT) to evaluate dynamic balance.
      21 healthy men (19+/-1 years) were asked to perform the FRT three times. The
      standard FRT was performed in the first and third trials. In the second trial,
      participants in a light-grip group (n = 11) were told to lightly grip (but to not
      apply force for mechanical support) the cane during the FRT. Participants in a
      depend-on-cane group (n = 10) were told to perform the FRT while supporting their
      weight with the cane. FRT is improved by not only supporting a person's own
      weight with a cane but also just lightly gripping the cane. These findings would
      be helpful in the development of a useful application to improve the human
      movement using a haptic sensory supplementation for activities of daily living. 

PMID- 26312076
TI  - A Robustness Comparison of Two Algorithms Used for EEG Spike Detection.
AB  - Spikes and sharp waves recorded on scalp EEG may play an important role in
      identifying the epileptogenic network as well as in understanding the central
      nervous system. Therefore, several automatic and semi-automatic methods have been
      implemented to detect these two neural transients. A consistent gold standard
      associated with a high degree of agreement among neuroscientists is required to
      measure relevant performance of different methods. In fact, scalp EEG data can
      often be corrupted by a set of artifacts and are not always served as data of
      gold standard. For this reason, the use of intracerebral EEG data mixed with
      gaussian noise seems to best resemble the output of scalp EEG brain and serves as
      a consistent gold standard. In the present framework, we test the robustness of
      two important methods that have been previously used for the automatic detection
      of epileptiform transients (spikes and sharp waves). These methods are based
      respectively on Discrete Wavelet Transform (DWT) and Continuous Wavelet Transform
      (CWT). Our purpose is to elaborate a comparative study in terms of sensitivity
      and selectivity changes via the decrease of Signal to Noise Ratio (SNR), which is
      ranged from 10 dB up to -10 dB. The results demonstrate that, DWT approach turns
      to be more stable in terms of sensitivity, and it successfully follows the
      detection of relevant spikes with the decrease of SNR. However, CWT-based
      approach remains more stable in terms of selectivity, so that, it performs well
      in terms of rejecting false spikes compared to DWT approach. 

PMID- 26312077
TI  - Accelerometer-based Physical Activity Monitoring in Patients with Knee
      Osteoarthritis: Objective and Ambulatory Assessment of Actual Physical Activity
      During Daily Life Circumstances.
AB  - BACKGROUND: It is important to assess physical activity objectively during daily
      life circumstances, to understand the association between physical activity and
      diseases and to determine the effectiveness of interventions. Accelerometer-based
      physical activity monitoring seems a promising method and could potentially
      capture all four FITT (i.e. Frequency, Intensity, Time, Type) components of
      physical activity considered by the World Health Organization (WHO). AIM: To
      assess the four FITT components of physical activity with an accelerometer during
      daily life circumstances and compare with self-reported levels of physical
      activity in patients with knee osteoarthritis (OA) and a healthy control group.
      METHODS: Patients (n=30) with end-stage knee OA and age-matched healthy subjects
      (n=30) were measured. An ambulant tri-axial accelerometer was placed onto the
      lateral side of the upper leg. Physical activity was measured during four
      consecutive days. Using algorithm-based peak detection methods in Matlab,
      parameters covering the four FITT components were assessed. Self-reported
      physical activity was assessed using the Short questionnaire to assess health
      enhancing physical activity (SQUASH). RESULTS: Knee OA patients demonstrated
      fewer walking bouts (154 +/-79 versus 215 +/-65 resp.; p=0.002), step counts
      (4402 +/-2960 steps/day versus 6943 +/-2581 steps/day; p=0.001) and sit-to-stand
      (STS) transfers (37 +/-14 versus 44 +/-12; p=0.031) compared to controls. Knee OA
      patients demonstrated more time sitting (65 +/-15% versus 57 +/-10% resp.;
      p=0.029), less time walking (8 +/-4% versus 11 +/-4% resp.; p=0.014) and lower
      walking cadence (87 +/-11steps/min versus 99 +/- 8steps/min resp.; p<0.001).
      Accelerometer-based parameters of physical activity were moderately-strong
      (Pearsons's r= 0.28-0.49) correlated to self-reported SQUASH scores. CONCLUSION:
      A single ambulant accelerometer-based physical activity monitor feasibly captures
      the four FITT components of physical activity and provides more insight into the
      actual physical activity behavior and limitations of knee OA patients in their
      daily life.

PMID- 26312078
TI  - A Comparative Study on the Influence of Probe Placement on Quality Assurance
      Measurements in B-mode Ultrasound by Means of Ultrasound Phantoms.
AB  - To check or to prevent failures in ultrasound medical systems, some tests should
      be scheduled for both clinical suitability and technical functionality
      evaluation: among them, image quality assurance tests performed by technicians
      through ultrasound phantoms are widespread today and their results depend on
      issues related to scanner settings as well as phantom features and operator
      experience. In the present study variations on some features of the B-mode image
      were measured when the ultrasound probe is handled by the technician in a routine
      image quality test: ultrasound phantom images from two array transducers are
      processed to evaluate measurement dispersion in distance accuracy, high contrast
      spatial resolution and penetration depth when probe is handled by the operator.
      All measurements are done by means of an in-house image analysis software that
      minimizes errors due to operator's visual acuity and subjective judgment while
      influences of ultrasound transducer position on quality assurance test results
      are estimated as expanded uncertainties on parameters above (measurement
      reproducibility at 95 percent confidence level): depending on the probe model,
      they ranged from +/-0.1 to +/-1.9 mm in high contrast spatial resolution, from +/
      0.1 to +/-5.5 percent in distance measurements error and from +/-1 to +/-10 mm in
      maximum depth of signal visualization. Although numerical results are limited to
      the two examined probes, they confirm some predictions based on general working
      principles of diagnostic ultrasound systems: (a) measurements strongly depend on
      settings as well on phantoms features, probes and parameters investigated; (b)
      relative uncertainty due to probe manipulation on spatial resolution can be very
      high, i.e. from 10 to more than 30 percent; 

PMID- 26312079
TI  - Evaluation of Glycemia Control Achieved by Glargine and Lispro Versus Detemir and
      Aspart Insulin Regimes in Type 2 Diabetics Undergoing Surgery.
AB  - There is paucity of scientific literature regarding the clinical outcome of long
      lasting basal insulin and rapid acting mealtime insulin regimes in surgical
      situations although employed in non-surgical situations. This study has evaluated
      the clinical outcome of two subcutaneous split-mixed Glargine+Lispro and
      Detemir+Aspart insulin regimes in type 2 diabetics undergoing surgery. 

PMID- 26312080
TI  - Effects of Bileaflet Mechanical Mitral Valve Rotational Orientation on Left
      Ventricular Flow Conditions.
AB  - We studied left ventricular flow patterns for a range of rotational orientations
      of a bileaflet mechanical heart valve (MHV) implanted in the mitral position of
      an elastic model of a beating left ventricle (LV). The valve was rotated through
      3 angular positions (0, 45, and 90 degrees) about the LV long axis. Ultrasound
      scans of the elastic LV were obtained in four apical 2-dimensional (2D) imaging
      projections, each with 45 degrees of separation. Particle imaging velocimetry was
      performed during the diastolic period to quantify the in-plane velocity field
      obtained by computer tracking of diluted microbubbles in the acquired ultrasound
      projections. The resulting velocity field, vorticity, and shear stresses were
      statistically significantly altered by angular positioning of the mechanical
      valve, although the results did not show any specific trend with the valve
      angular position and were highly dependent on the orientation of the imaging
      plane with respect to the valve. We conclude that bileaflet MHV orientation
      influences hemodynamics of LV filling. However, determination of 'optimal' valve
      orientation cannot be made without measurement techniques that account for the
      highly 3-dimensional (3D) intraventricular flow. 

PMID- 26312082
TI  - Editorial "Role of Iatrogenic Factors in Dentistry" "An Ounce of Prevention Worth
      a Pound of Care".

PMID- 26312081
TI  - Blunt Thoracic Aortic Injuries: New Perspectives in Management.
AB  - Blunt thoracic aortic injuries (BTAIs) present a great challenge because of their
      potentially fatal outcomes. Recent advancements in their management have proved
      to be beneficial in terms of various parameters, including mortality and
      complications. Endovascular repair is now the treatment of choice in most centres
      and is continuously replacing the traditional open surgical method. We present a
      mini-review of the most recent relevant literature that briefly describes the
      major shifts in the diagnosis and treatment of BTAIs and compares the outcomes of
      the conventional surgical approach to those of the endovascular method for the
      definitive repair of these injuries. Although both the reviewed literature and
      the most recently published guidelines are in support of the use of the
      endovascular approach, as short and midterm results are promising, its long-term
      outcomes still remain in question. 

PMID- 26312083
TI  - Iatrogenic Damage to the Periodontium Caused by Radiation and Radiotherapy.
AB  - The radio-sensitivity of a tissue or organ is measured by its response to
      irradiation. Loss of moderate numbers of cells does not affect the function of
      most organs. However, with loss of large numbers of cells, all affected organisms
      display a clinical result. The severity of this change depends on the dosage and
      thus the extent of cell loss. Moderate doses to a localized area may lead to
      repairable damage. Comparable doses to a whole organism may result in death from
      damage to the most sensitive systems in the body. 

PMID- 26312084
TI  - Iatrogenic Damage to the Periodontium Caused by Removable Prosthodontic Treatment
      Procedures: An Overview.
AB  - As the number of aged people in the world is growing, the need to provide
      patients with tooth alternate through removable partial dentures is equally
      growing. There are adversarial effects that should be kept in mind which might
      disturb the remaining teeth; specially, the abutments and the supporting tissues.
      These effects might spread to the muscles of mastication and also to the
      supporting periodontal tissues. Thus, we should plan removable partial dentures
      (RPDs) without mutilation to the adjacent teeth or the underlying tissues. 

PMID- 26312085
TI  - Iatrogenic Damage to the Periodontium Caused by Exodontic Treatment Procedures:
      An Overview.
AB  - Dentists encounter a wide range of hard-tissue injuries in practice. Dental
      extractions are one of the most common procedures in dentistry and may lead to
      several complications, including oral sinus complications, osteitis, infection,
      dysesthesia, pain, and bleeding. 

PMID- 26312086
TI  - Iatrogenic Damage to the Periodontium Caused by Implants and Implant Treatment
      Procedures.
AB  - A dental implant (also known as an endosseous implant or fixture) is a surgical
      component that interfaces with the bone of the jaw or skull to support a dental
      prosthesis such as a crown, bridge, denture, facial prosthesis or to act as an
      orthodontic anchor.Well planned, comprehensive treatment plans lead to successful
      implant treatment and patient satisfaction, which are the eventual long-term
      objectives. Probability of implant success can be put at jeopardy by absolute and
      relative risk factors. 

PMID- 26312087
TI  - Iatrogenic Damage to the Periodontium Caused by Periodontal Treatment Procedures.
AB  - Periodontitis is an inflammatory disease affecting the periodontium i.e. the
      tissues that surround and support the teeth. Periodontitis manifests as
      progressive loss of the alveolar bone around the teeth, and if left untreated,
      can cause loosening and subsequent loss of teeth. Periodontitis is initiated by
      microorganisms that adhere to and grow on the tooth's surfaces, besides an over 
      aggressive immune response against these microorganisms. The primary goal of
      periodontal therapy is to preserve the natural dentition by accomplishing and
      preserving a healthy functional periodontium. Many treatment modalities have been
      introduced to improve the therapeutic result of periodontal treatment which may
      also damage the periodontiumiatrogenically. 

PMID- 26312088
TI  - Iatrogenic Factors Affecting the Periodontium: An Overview.
AB  - The principal reason of gingival inflammation is bacterial plaque, along with
      other predisposing factors. These predisposing factors are calculus,
      malocclusion, faulty restorations, complications associated with orthodontic
      therapy, self- inflicted injuries, use of tobacco & radiation therapy. The
      contributing factors to gingival inflammation & periodontal destruction are
      deficient dental restorations and prosthesis. Inadequate dental procedures that
      add to the weakening of the periodontal tissues are referred to as iatrogenic
      factors. 

PMID- 26312089
TI  - Iatrogenic Damage to the Periodontium Caused by Laser: An Overview.
AB  - Lasers have been used in dentistry since 1994 to treat a number of dental
      problems. A variety of lasers are now available for use in dentistry. Once stated
      as an intricate technology with restricted usage in clinical dentistry, there is
      a growing awareness of the usefulness of lasers in the armamentarium of the
      modern dental practice, where they can be used as an adjunct or alternative to
      various long-standing approaches. 

PMID- 26312090
TI  - Iatrogenic Damage to the Periodontium Caused by Endodontic Treatment Procedures:
      An Overview.
AB  - The tooth, the pulp tissue within it and its supporting structures should be
      viewed as one biologic unit. The interrelationship of these structures influences
      each other during health, function and disease. The interrelationship between
      periodontal and endodontic diseases has aroused much speculation, confusion and
      controversy. The endodontium and periodontiumare closely related and disease or
      damage of one tissue may lead to the involvement of the other. 

PMID- 26312091
TI  - Iatrogenic Damage to Periodontium by Restorative Treatment Procedures: An
      Overview.
AB  - The regenerative capability found in most other tissues is not possessed by
      teeth. Hence, enamel or dentin once lost as a result of caries, trauma, wear, and
      restorative materials must be replaced to restore form and function. Teeth
      require preparation to receive restorations, and these preparations must be based
      on fundamental principles from which basic criteria can be developed to help
      predict the success of restorative treatment. 

PMID- 26312092
TI  - Iatrogenic Damage to the Periodontium by Chemicals and Dental Materials.
AB  - The toxicity and tissue reactions to dental materials are receiving more
      attention as a wide variety of materials are used and as federal agencies
      demonstrate more concern in this area. A further indication of the importance of
      the interaction of materials and tissues is the development of recommended
      standard practices and tests for the biological interaction of materials. 

PMID- 26312093
TI  - Iatrogenic Damage to the Periodontium Caused by Orthodontic Treatment Procedures:
      An Overview.
AB  - In orthodontic treatment, teeth are moved in to new positions and relationships
      and the soft tissue and underlying bone are altered to accommodate changes in
      esthetics and function. Function is more important than esthetics. The speciality
      of orthodontics has in addition to its benefits, complications as well as risks
      associated with its procedures. However the benefits outweigh the risks &
      complications in most of the treatment cases. Few of the unwanted side effects
      associated with treatment are tooth discolorations, enamel decalcification,
      periodontal complications like open gingival embrasures, root resorption,
      allergic reactions to nickel & chromium as well as treatment failure in the form
      of relapse. 

PMID- 26312094
TI  - Improving Composite Resin Performance Through Decreasing its Viscosity by
      Different Methods.
AB  - The aim of this work was to present the different current methods of decreasing
      viscosity of resin composite materials such as (using flowable composites,
      lowering the viscosity of the monomer mixture, heating composites and applying
      sonic vibration) and furnish dentists with a basis that can provide criteria for
      choosing one or another to suit their therapeutic requirements. The four
      discussed methods proved that lowering composite viscosity improves its handling
      and facilitates its application to cavities with complicated forms, decreasing
      time for procedure and improving marginal adaptation. Other properties improved
      by decreasing composite resin viscosity were controversial between the four
      methods and affected by other factors such as composite brand and light cure
      unit. 

PMID- 26312095
TI  - The Effect of Flapless and Full-thickness Flap Techniques on Implant Stability
      During the Healing Period.
AB  - PURPOSE: When soft tissue flaps are reflected for implant placement, the blood
      supply from the periosteum to the bone is disrupted. The aim of this study was to
      compare the effects of the flapless (FL) and full-thickness flap (FT) techniques
      on implant stability. Methods : Nine patients received 22 implants. The implants
      were placed using the FL technique on the contralateral side of the jaw; the FT
      technique was used as the control technique. Resonance frequency analysis (RFA)
      was performed at the time of implant placement and at 6 and 12 weeks after
      implant placement. RFA values were compared between the FL and FT groups and
      between time intervals in the same group. Results : The median (interquartile
      range [IQR]) RFA values at the time of implant placement were 75.00 (15.00) for
      the FL technique and 75.00 (9.00) for the FT technique. At 6 weeks, the median
      (IQR) values were 79 (3.30) for the FL technique and 80 (12.70) for the FT
      technique. At 12 weeks, the median (IQR) values were 82.3 (3.30) for the FL
      technique and 82.6 (8.00) for the FT technique. There were no significant
      differences between the 2 techniques at the time of implant placement, after 6
      weeks or after 12 weeks, with p values of 0.994, 0.789, and 0.959, respectively.
      There were significant differences between the RFA values at the time of implant
      placement and after 6 weeks for the FL technique (p=0.028) but not for the FT
      technique (p=0.091). There were also significant differences between the RFA
      values at 6 weeks and the RFA values at 12 weeks for the FL technique (p=0.007)
      and for the FT technique (p=0.003). Conclusion : Periosteum preservation during
      the FL procedure will speed up bone remodeling and result in early secondary
      implant stability as well as early loading.

PMID- 26312097
TI  - Cinnamon-induced Oral Mucosal Contact Reaction.
AB  - Contact stomatitis associated with consumption of cinnamon flavoring agents is a
      relatively uncommon disorder. Of relevance, both clinical features and the
      histopathologic findings of this condition are nonspecific, and, more
      importantly, may resemble some other inflammatory oral mucosa disorders,
      eventually making diagnosis difficult. Usually a patient exhibits a combination
      of white and erythematous patches of abrupt onset, accompanied by a burning
      sensation. To shed some light on this subject, a case of a 64-year-old woman with
      hypersensitivity contact reaction on the oral mucosa due to cinnamon mints is
      presented, with emphasis on differential diagnosis and the process for
      confirmation of the diagnosis. The treatment consists of discontinuing the use of
      cinnamon products. Clinicians will be able to recognize this disorder following a
      careful clinical examination and detailed history. This recognition is important
      in order to avoid invasive and expensive diagnostic procedures. 

PMID- 26312096
TI  - Dental Evidence in Forensic Identification - An Overview, Methodology and Present
      Status.
AB  - Forensic odontology is primarily concerned with the use of teeth and oral
      structures for identification in a legal context. Various forensic odontology
      techniques help in the identification of the human remains in incidents such as
      terrorists' attacks, airplane, train and road accidents, fires, mass murders, and
      natural disasters such as tsunamis, earth quakes and floods, etc. (Disaster
      Victim Identification-DVI). Dental structures are the hardest and well protected
      structures in the body. These structures resist decomposition and high
      temperatures and are among the last ones to disintegrate after death. The
      principal basis of the dental identification lies in the fact that no two oral
      cavities are alike and the teeth are unique to an individual. The dental evidence
      of the deceased recovered from the scene of crime/occurrence is compared with the
      ante-mortem records for identification. Dental features such as tooth morphology,
      variations in shape and size, restorations, pathologies, missing tooth, wear
      patterns, crowding of the teeth, colour and position of the tooth, rotations and
      other peculiar dental anomalies give every individual a unique identity. In
      absence of ante-mortem dental records for comparison, the teeth can help in the
      determination of age, sex, race/ethnicity, habits, occupations, etc. which can
      give further clues regarding the identity of the individuals. This piece of
      writing gives an overview of dental evidence, its use in forensic identification
      and its limitations. 

PMID- 26312098
TI  - Acute Respiratory Failure: Pathophysiological Basis From A Multidisciplinary
      Clinical Approach.

PMID- 26312100
TI  - Transfusion-Related Acute Lung Injured (TRALI): Current Concepts.
AB  - Transfusion-related acute lung injury (TRALI) is a life-threatening intervention
      that develops within 6 hours of transfusion of one or more units of blood, and is
      an important cause of morbidity and mortality resulting from transfusion. It is
      necessary to dismiss other causes of acute lung injury (ALI), like sepsis, acute
      cardiogenic edema, acute respiratory distress syndrome (ARDS) or bacterial
      infection. There are two mechanisms that lead to the development of this
      syndrome: immune-mediated and no immune- mediated TRALI. A common theme among the
      experimental TRALI models is the central importance of neutrophils in mediating
      the early immune response, and lung vascular injury. Central clinical symptoms
      are dyspnea, tachypnea, tachycardia, cyanosis and pulmonary secretions,
      altogether with other hemodynamic alterations, such as hypotension and fever.
      Complementary to these clinical findings, long-term validated animal models for
      TRALI should allow the determination of the cellular targets for TRALI-inducing
      alloantibodies as well as delineation of the underlying pathogenic molecular
      mechanisms, and key molecular mediators of the pathology. Diagnostic criteria
      have been established and preventive measures have been implemented. These
      actions have contributed to the reduction in the overallnumber of fatalities.
      However, TRALI still remains a clinical problem. Any complication suspected of
      TRALI should immediately be reported. 

PMID- 26312099
TI  - Pathophysiological Approaches of Acute Respiratory Distress syndrome: Novel Bases
      for Study of Lung Injury.
AB  - Experimental approaches have been implemented to research the lung damage related
      mechanism. These models show in animals pathophysiological events for acute
      respiratory distress syndrome (ARDS), such as neutrophil activation, reactive
      oxygen species burst, pulmonary vascular hypertension, exudative edema, and other
      events associated with organ dysfunction. Moreover, these approaches have not
      reproduced the clinical features of lung damage. Lung inflammation is a relevant
      event in the develop of ARDS as component of the host immune response to various
      stimuli, such as cytokines, antigens and endotoxins. In patients surviving at the
      local inflammatory states, transition from injury to resolution is an active
      mechanism regulated by the immuno-inflammatory signaling pathways. Indeed,
      inflammatory process is regulated by the dynamics of cell populations that
      migrate to the lung, such as neutrophils and on the other hand, the role of the
      modulation of transcription factors and reactive oxygen species (ROS) sources,
      such as nuclear factor kappaB and NADPH oxidase. These experimental animal models
      reproduce key components of the injury and resolution phases of human ALI/ARDS
      and provide a methodology to explore mechanisms and potential new therapies. 

PMID- 26312101
TI  - Pathophysiological Basis of Acute Respiratory Failure on Non-Invasive Mechanical
      Ventilation.
AB  - Noninvasive mechanical ventilation (NIMV) was created for patients who needed
      noninvasive ventilator support, this procedure decreases the complications
      associated with the use of endotracheal intubation (ETT). The application of NIMV
      has acquired major relevance in the last few years in the management of acute
      respiratory failure (ARF), in patients with hypoxemic and hypercapnic failure.
      The main advantage of NIMV as compared to invasive mechanical ventilation (IMV)
      is that it can be used earlier outside intensive care units (ICUs). The evidence
      strongly supports its use in patients with COPD exacerbation, support in weaning
      process in chronic obstructive pulmonary disease (COPD) patients, patients with
      acute cardiogenic pulmonary edema (ACPE), and Immunosuppressed patients. On the
      other hand, there is poor evidence that supports the use of NIMV in other
      pathologies such as pneumonia, acute respiratory distress syndrome (ARDS), and
      during procedures as bronchoscopy, where its use is still controversial because
      the results of these studies are inconclusive against the decrease in the rate of
      intubation or mortality. 

PMID- 26312102
TI  - Humidification on Ventilated Patients: Heated Humidifications or Heat and
      Moisture Exchangers?
AB  - The normal physiology of conditioning of inspired gases is altered when the
      patient requires an artificial airway access and an invasive mechanical
      ventilation (IMV). The endotracheal tube (ETT) removes the natural mechanisms of
      filtration, humidification and warming of inspired air. Despite the noninvasive
      ventilation (NIMV) in the upper airways, humidification of inspired gas may not
      be optimal mainly due to the high flow that is being created by the leakage
      compensation, among other aspects. Any moisture and heating deficit is
      compensated by the large airways of the tracheobronchial tree, these are poorly
      suited for this task, which alters mucociliary function, quality of secretions,
      and homeostasis gas exchange system. To avoid the occurrence of these events,
      external devices that provide humidification, heating and filtration have been
      developed, with different degrees of evidence that support their use. 

PMID- 26312103
TI  - Ventilator-Induced Lung Injury (VILI) in Acute Respiratory Distress Syndrome
      (ARDS): Volutrauma and Molecular Effects.
AB  - Acute Respiratory Distress Syndrome (ARDS) is a clinical condition secondary to a
      variety of insults leading to a severe acute respiratory failure and high
      mortality in critically ill patients. Patients with ARDS generally require
      mechanical ventilation, which is another important factor that may increase the
      ALI (acute lung injury) by a series of pathophysiological mechanisms, whose
      common element is the initial volutrauma in the alveolar units, and forming part
      of an entity known clinically as ventilator-induced lung injury (VILI). Injured
      lungs can be partially protected by optimal settings and ventilation modes, using
      low tidal volume (VT) values and high positive-end expiratory pressure (PEEP).
      The benefits in ARDS outcomes caused by these interventions have been confirmed
      by several prospective randomized controlled trials (RCTs) and are attributed to
      reduction in volutrauma. The purpose of this article is to present an approach to
      VILI pathophysiology focused on the effects of volutrauma that lead to lung
      injury and the 'mechanotransduction' mechanism. A more complete understanding
      about the molecular effects that physical forces could have, is essential for a
      better assessment of existing strategies as well as the development of new
      therapeutic strategies to reduce the damage resulting from VILI, and thereby
      contribute to reducing mortality in ARDS. 

PMID- 26312104
TI  - Noninvasive Mechanical Ventilation in Acute Respiratory Failure Patients: A
      Respiratory Therapist Perspective.
AB  - Physiotherapist in Chile and Respiratory Therapist worldwide are the
      professionals who are experts in respiratory care, in mechanical ventilation
      (MV), pathophysiology and connection and disconnection criteria. They should be
      experts in every aspect of the acute respiratory failure and its management, they
      and are the ones who in medical units are able to resolve doubts about
      ventilation and the setting of the ventilator. Noninvasive mechanical ventilation
      should be the first-line of treatment in acute respiratory failure, and the
      standard of care in severe exacerbations of chronic obstructive pulmonary
      disease, acute cardiogenic pulmonary edema, and in immunosuppressed patients with
      high levels of evidence that support the work of physiotherapist. Exist other
      considerations where most of the time, physicians and other professionals in the
      critical units do not take into account when checking the patient ventilator
      synchrony, such as the appropriate patient selection, ventilator selection, mask
      selection, mode selection, and the selection of a trained team in NIMV. The
      physiotherapist needs to evaluate bedside; if patients are properly connected to
      the ventilator and in a synchronously manner. In Chile, since 2004, the
      physioterapist are included in the guidelines as a professional resource in the
      ICU organization, with the same skills and obligations as those described in the
      literature for respiratory therapists. 

PMID- 26312105
TI  - Effect of Adalimumab on Work Ability Assessed in Rheumatoid Arthritis Disease
      Patients in Saudi Arabia (AWARDS).
AB  - OBJECTIVES: Rheumatoid arthritis (RA) is a chronic disabling disease that can
      jeopardize the ability of affected individuals to participate in paid work. Our
      objective was to evaluate the effectiveness of a 6-month course of tumor necrosis
      factor (TNF) antagonist (adalimumab) on work ability, overall health, and fatigue
      in RA patients. METHODS: Between October 2012 and February 2014, this
      prospective, observational study enrolled 63 consecutive patients with
      established adult RA at outpatient clinics in Makkah, Jeddah, Riyadh and Abha
      (Saudi Arabia). Patients received subcutaneous injections of adalimumab (40 mg
      every 2 weeks). Outcomes were measured at baseline and 6 months using the
      following tools: Work Productivity and Activity Impairment (WPAI), Health
      Assessment Questionnaire Disability Index (HAQ-DI), Fatigue Severity Scale (FSS),
      Visual Analog Scale for Fatigue (VAS-F), and work disability self-assessment.
      RESULTS: All outcomes showed improvements after 6 months of adalimumab therapy.
      Significant improvements from baseline were observed in absenteeism (64% +/-
      11.62 to 11.60% +/- 11.17 [p<0.0001]), presenteeism (62.15% +/- 20.11 to 34.92%
      +/- 20.61 [p<0.0001]), overall work impairment (69.08% +/- 18.86 to 40.73% +/-
      22.29 [p<0.0001]), overall activity impairment (68.46% +/- 18.58 to 36.46% +/-
      20.79 [p<0.0001]), HAQ score (1.69 +/- 0.57 to 0.81 +/- 0.61 [p<0.0001]), and FSS
      score (47.08 +/- 9.55 to 27.86 +/- 13.43 [p<0.0001]). CONCLUSION: A 6-month
      course of adalimumab improved work ability, fatigue, and overall health
      assessments in patients with established RA. Our findings encourage randomized
      controlled trials investigating the cost-effectiveness and long-term effects of
      TNF inhibitors on work disability.

PMID- 26312106
TI  - Sex Differences in the Effects of a Biological Drug for Rheumatoid Arthritis on
      Depressive State.
AB  - OBJECTIVE: Sex-specific medicine has attracted attention in recent years, but no
      report on rheumatoid arthritis (RA) has examined sex differences in the
      effectiveness of biologics on activities of daily living (ADL), quality of life
      (QOL), or depressive state. METHODS: The study subjects were 161 RA patients
      (female: 138; male: 23) attending regular doctor visits at our hospital. We
      compared the changes in disease activity, which was evaluated using the
      simplified disease activity index (SDAI), ADL (using the modified health
      assessment questionnaire; mHAQ), QOL (using short form-36; SF-36), and the
      Hamilton Depression Rating Scale (HAM-D) for RA patients between each sex over a
      six-month observation period while administering biologic treatment. RESULTS: The
      female patients reported significant improvements in the following metrics: SDAI:
      from 22.1 +/- 11.9 to 8.9 +/- 7.8 (p < 0.001); mHAQ: from 0.46 +/- 0.50 to 0.32
      +/- 0.45 (p < 0.001); and HAM-D: from 6.2 +/- 4.8 to 3.8 +/- 4.1 (p < 0.001).
      Moreover, all eight items of the SF-36 were significantly improved (p < 0.01). In
      contrast, the male patients improved on the SDAI (from 27.9 +/- 11.7 to 12.7 +/-
      8.6 (p < 0.001)), but we did not observe significant improvements in the mHAQ or
      HAM-D scores or in any items on the SF-36. CONCLUSION: Both male and female
      patients with RA improved when using a biological drug. Sex differences in the
      improvement of depressive state were observed.

PMID- 26312107
TI  - LETTER TO THE EDITOR Atypical Granulomatous Myositis and Pulmonary Sarcoidosis.

PMID- 26312108
TI  - In Vivo Bioluminescence Imaging - A Suitable Method to Track Mesenchymal Stromal
      Cells in a Skeletal Muscle Trauma.
AB  - Cell-based therapies have emerged during the last decade in various clinical
      fields. Especially mesenchymal stromal cells (MSCs) have been used in pre
      clinical and clinical applications in cardiovascular, neurodegenerative and
      musculoskeletal disorders. In order to validate survival and viability as well as
      possible engraftment of MSCs into the host tissue a live cell imaging technique
      is needed that allows non-invasive, temporal imaging of cellular kinetics as well
      as evaluation of cell viability after transplantation. In this study we used
      luciferase-based bioluminescence imaging (BLI) to investigate the survival of
      autologous MSCs transplanted into a severely crushed soleus muscle of the rats.
      Furthermore we compared local as well as intra-arterial (i.a.) administration of
      cells and analyzed if luciferase transduced MSCs depict the same characteristics
      in vitro as non-transduced MSCs. We could show that transduction of MSCs does not
      alter their in vitro characteristics, thus, transduced MSCs display the same
      differentiation, proliferation and migration capacity as non-transduced cells.
      Using BLI we could track MSCs transplanted into a crushed soleus muscle until day
      7 irrespective of local or i.a. APPLICATION: Hence, our study proves that
      luciferase-based BLI is a suitable method for in vivo tracking of MSCs in
      skeletal muscle trauma in rats.

PMID- 26312109
TI  - A Rare Case of Femoral Neuropathy Associated with Ilio-Psoas Bursitis After 10
      Years of Total Hip Arthroplasty.
AB  - We describe a case of femoral nerve palsy caused due to non-infective large
      iliopsoas bursitis after 10 years of cementless ceramic-on-metal THA. Bursectomy
      and exploration of femoral nerve were done to relieve the compressive symptoms of
      femoral nerve. Patient neurological symptoms were recovered within six months.
      Iliopsoas bursitis after THA can lead to anterior hip pain, lump in inguinal area
      or abdomen, limb swelling due to venous compression or more rarely neurovascular
      compressive symptoms depending on size and extension. Treating physician should
      be aware of this rare condition after THA in the absence of any radiographic
      findings so that prompt diagnosis and treatment can be carried out. 

PMID- 26312110
TI  - Polytrauma.

PMID- 26312111
TI  - Current Concepts in Orthopedic Management of Multiple Trauma.
AB  - Multiple trauma patients frequently present challenging clinical scenarios with
      musculoskeletal injuries being the most common indications for surgical
      procedures in these patients. Despite our substantial knowledge, a universally
      approved objective definition for "multiple trauma" is yet to be delineated.
      Several controversial aspects of economics, pathophysiology, animal models,
      diagnosis, management and outcome of patients with multiple trauma have recently
      been explored and although some progress has been made, it seems that the
      available evidence is still inconclusive in some occasions. This manuscript
      revisits several current concepts of multiple trauma that have been the focus of
      recent investigation. We aim to provide the reader with an updated perspective
      based on the most recently published literature in the field of multiple trauma. 

PMID- 26312113
TI  - Orthopaedic Timing in Polytrauma in a Second Level Emergency Hospital. An
      Overrated Problem?
AB  - The main concern for orthopaedic treatment in polytrauma has always been the same
      for almost forty years, which also regards "where" and "when" to proceed; correct
      surgical timing and correct interpretation of the DCO concept are still being
      debated. In the last few years, several attempts have been made to classify
      patients based on their clinical presentation and by trying to figure out which
      vital parameters are able to predict the patient's outcome. This study evaluated
      all patients who presented with code red at the Emergency Department of our
      Hospital, a level II trauma center. For every patient, the following
      characteristics were noted: sex, age, day of hospitalization, orthopaedic trauma,
      time to surgery, presence of an associated surgical condition in the fields of
      general surgery, thoracic surgery, neurosurgery and vascular surgery, cardiac
      frequency, blood pressure, oxygen saturation, Glasgow Coma Scale and laboratory
      data. All patients included were divided into subgroups based on orthopaedic
      surgical timing. Two other subgroups were also identified and analyzed in detail:
      deceased and weekend traumas. A total of 208 patients were included. Our primary
      goal was to identify a correlation between the mortality and surgical timing of
      the orthopaedic procedures; our secondary goal was to recognize, if present, a
      statistically relevant association between historical, clinical and laboratory
      data, and mortality rate, defining any possible risk factor. A correlation
      between mortality and orthopaedic surgical timing was not found. Analyzing
      laboratory data revealed an interesting correlation between mortality and: blood
      pressure, platelet count, cardiac frequency, hematocrit, hemoglobin and age. 

PMID- 26312112
TI  - Resuscitation of Polytrauma Patients: The Management of Massive Skeletal
      Bleeding.
AB  - The term 'severely injured patient' is often synonymous of polytrauma patient,
      multiply-injured patient or, in some settings, polyfractured patient. Together
      with brain trauma, copious bleeding is the most severe complication of
      polytrauma. Consequently hypotension develop. Then, the perfusion of organs may
      be compromised, with the risk of organ failure. Treatment of chest bleeding after
      trauma is essential and is mainly addressed via surgical manoeuvres. As in the
      case of lesions to the pelvis, abdomen or extremities, this approach demonstrates
      the application of damage control (DC). The introduction of sonography has
      dramatically changed the diagnosis and prognosis of abdominal bleeding. In stable
      patients, a contrast CT-scan should be performed before any x-ray projection,
      because, in an emergency situation, spinal or pelvic fractures be missed by
      conventional radiological studies. Fractures or dislocation of the pelvis causing
      enlargement of the pelvic cavity, provoked by an anteroposterior trauma, and in
      particular cases presenting vertical instability, are the most severe types and
      require fast stabilisation by closing the pelvic ring diameter to normal
      dimensions and by stabilising the vertical shear. Controversy still exists about
      whether angiography or packing should be used as the first choice to address
      active bleeding after pelvic ring closure. Pelvic angiography plays a significant
      complementary role to pelvic packing for final haemorrhage control. Apart from
      pelvic trauma, fracture of the femur is the only fracture provoking acute life
      threatening bleeding. If possible, femur fractures should be immobilised
      immediately, either by external fixation or by a sheet wrap around both
      extremities. 

PMID- 26312114
TI  - Pelvic Fractures in Paediatric Polytrauma Patients: Classification, Concomitant
      Injuries and Early Mortality.
AB  - PURPOSE OF THIS STUDY: To review the characteristics, concomitant injuries and
      mortality in children with polytrauma and associated pelvic fractures treated in
      a Level-I Trauma Centre. MATERIALS AND METHODS: Between December 2003 and
      November 2013, 49 children with an Injury Severity Score (ISS) of 16 or greater
      and a pelvic fracture met the inclusion criteria and were evaluated. The
      mortality, transfusion requirements and length of intensive care unit stay were
      correlated with the ISS, Abbreviated Injury Scale, concomitant limb and spine
      fractures, and type of pelvic ring injury (AO/OTA classification). RESULTS: The
      mean ISS at presentation was 31.4 (range 16 to 57). 19 (38.7%) patients sustained
      a Type A, 27 (55.1%) a Type B and 3 (6.2%) a Type C injury. Head and face trauma
      was present in 33 (67.3%) cases. Blood transfusion during the resuscitation
      process was necessitated in six (12.2%) patients. Thirty-eight (77.5%) patients
      were managed non-operatively for their pelvic injuries. The mean duration of
      hospital stay was 23.9 days (range 1 to 146 days). In this cohort of polytrauma
      paediatric patients there were five (10.2%) mortalities (all suffered an
      associated head trauma ) within 30 days from the initial injury. CONCLUSION:
      Severe head injury and a high ISS are significantly associated with mortality in
      children with pelvic fractures. These patients have a high incidence of
      concomitant spine and chest injuries Hemorrhage due to pelvic injuries is rare.
      Severe head injuries predict a longer ICU stay in this population.

PMID- 26312115
TI  - Methods and Guidelines for Venous Thromboembolism Prevention in Polytrauma
      Patients with Pelvic and Acetabular Fractures.
AB  - Sequential compression devices and chemical prophylaxis are the standard venous
      thromboembolism (VTE) prevention for trauma patients with acetabular and pelvic
      fractures. Current chemical pharmacological contemplates the use of heparins or
      fondaparinux. Other anticoagulants include coumarins and aspirin, however these
      oral agents can be challenging to administer and may need monitoring. When
      contraindications to anticoagulation in high-risk patients are present,
      prophylactic inferior vena cava filters can be an option to prevent pulmonary
      emboli. Unfortunately strong evidence about the most effective method, and the
      timing of their commencement, in patients with pelvic and acetabular fractures
      remains controversial. 

PMID- 26312116
TI  - Retained Sponge: A Rare Complication in Acetabular Osteosinthesis.
AB  - Retained sponges after a surgical treatment of polytrauma may cause a broad
      spectrum of clinical symptoms and present a difficult diagnostic problem. We
      report a case of retained surgical sponge in a 35-year-old man transferred from
      another hospital, that sustained a open acetabular fracture. The fracture was
      reduced through a limited ilio-inguinal approach. After 4 days, he presented
      massive wound dehiscence of the surgical approach. An abdominal CT scan showed,
      lying adjacent to the outer aspect of the left iliac crest, a mass of 10 cm,
      identified as probable foreign body. The possibility of this rare complication
      should be in the differential diagnosis of any postoperative patient who presents
      with pain, infection, or palpable mass. 

PMID- 26312117
TI  - Timing of Femoral Shaft Fracture Fixation Affects Length of Hospital Stay in
      Patients with Multiple Injuries.
AB  - PURPOSE: Appropriate timing of definitive fracture care in the setting of
      polytrauma remains controversial. The aim of this study is to determine whether
      timing of definitive fixation of femur fractures impacts subsequent length of
      hospital stay, a surrogate for postoperative morbidity, in patients with multi
      system trauma. METHODS: Secondary analysis of data from the National Trauma Data
      Bank (January 1, 2000 to December 31, 2004) was performed. Adult patients who:
      (1) had an open or closed femoral shaft fracture, (2) had an injury severity
      score (ISS) greater than or equal to 15, (3) and underwent definitive internal
      fixation were included. Time to fixation was divided into 5 time periods based on
      commonly used cut-off points from the literature: (1) 12 hours or less, (2)
      between 12 and 24 hours, (3) between 24 and 48 hours, (4) between 48 and 120
      hours, and (5) more than 120 hours. Because we consider length of stay a
      surrogate for adverse outcome causally affected by treatment time, the outcome
      variable was calculated as the duration of hospitalization following definitive
      treatment. Time to definitive fixation and its effect on post-treatment length of
      hospital stay was analyzed using median regression with inverse probability of
      treatment-weighting (IPTW) to control for confounding factors. RESULTS: Compared
      to fixation during the first 12 hours after admission, median length of hospital
      stay was significantly higher (2.77 days; 95% confidence interval, 0.54 to 4.72)
      when fixation occurred between 48 and 120 hours from admission. Among the other
      time intervals, only treatment between twelve to twenty-four hours after
      admission was shown to reduce length of stay (-0.61 days; 95% confidence
      interval, -1.53 to 0.42) versus the referent interval of the first 12 hours,
      though this result did not achieve statistical significance. In order to assess
      the impact of shorter recorded length of stay for deceased patients, sensitivity
      analysis was conducted excluding all patient that underwent definitive treatment
      and died. Results were nearly identical for the second analysis, showing a higher
      post-treatment length of stay estimated for the population treated between 48 and
      120 hours versus had they been treated within the first 12 hours from admission
      (2.53 days, 95% confidence interval, 0.27 to 4.13). CONCLUSION: Delayed fixation
      of femoral shaft fractures in patients with multiple injuries between 2-5 days
      may lead to an increase in adverse outcomes as evidenced by increased median
      length of hospital stay. This finding supports prior clinical reports of a
      perilous period where a "second hit" resulting from definitive internal fixation
      can occur. Whether there is an optimal window for fixation during which
      physiologic stress of fracture fixation does not adversely lengthen hospital stay
      should be the subject of future prospective study.

PMID- 26312118
TI  - Periarticular Fractures of the Knee in Polytrauma Patients.
AB  - Periarticular fractures around the knee are a challenge for the orthopaedic
      surgeon. When these fractures are presented in the context of a multiple trauma
      patient, they are even more difficult to manage because the treatment approach
      depends not only on the fracture itself, but also on the patient's general
      condition. These fractures, caused by high-energy trauma, present complex
      fracture patterns with severe comminution and major loss of articular congruity,
      and are often associated with vascular and nerve complications, particularly in
      the proximal tibia, due to its anatomical features with poor myocutaneous
      coverage. They are almost always accompanied by soft tissue injury. The
      management of polytrauma patients requires a multidisciplinary team and accurate
      systemic stabilization of the patient before undertaking orthopaedic treatment.
      These fractures are usually addressed sequentially, either according to the
      general condition of the patient or to the local characteristics of the lesions.
      In recent decades, various fixation methods have been proposed, but there is
      still no consensus as to the ideal method for stabilizing these fractures. In
      this paper, we describe the general characteristics of these fractures, the
      stabilization methods traditionally used and those that have been developed in
      recent years, and discuss the treatment sequences proposed as most suitable for
      the management of these injuries. 

PMID- 26312119
TI  - Management of the Floating Knee in Polytrauma Patients.
AB  - Ipsilateral fracture of the femur and tibia, or floating knee, is a rare injury
      that is found almost exclusively in polytrauma or high-energy trauma patients. It
      presents a combination of diaphyseal, metaphyseal and intra-articular fractures
      of the femur and tibia, with a high incidence of neurovascular, ligamentous and
      soft-tissue injuries. The functional outcome and, in some cases, the life, of
      such polytrauma patients depends largely on a correct therapeutic approach being
      taken. In general, the treatment decided upon will depend on the individual
      characteristics present, regarding aspects such as the patient's general
      condition, the fracture line and the state of the soft tissues. The treatment
      provided may be the same as when single fractures are presented, but it is often
      necessary to consider whether certain techniques or surgical approaches may
      interfere with other lines of treatment. It is essential at all times to take
      into consideration the associated injuries and complications before deciding upon
      a treatment strategy. Ligamentous injuries play an important role in these
      injuries, much more so than when fractures occur singly. Therefore, these
      injuries require management by an experienced multidisciplinary team. 

PMID- 26312120
TI  - Low Energy Trauma in Older Persons: Where to Next?
AB  - The global population is increasing rapidly with older persons accounting for the
      greatest proportion. Associated with this rise is an increased rate of injury,
      including polytrauma, for which low energy falls has become the main cause. The
      resultant growing impact on trauma resources represents a major burden to the
      health system. Frailty, with its related issues of cognitive dysfunction and
      sarcopenia, is emerging as the unifying concept that relates both to the initial
      event and subsequent outcomes. Strategies to better assess and manage frailty are
      key to both preventing injury and improving trauma outcomes in the older
      population and research that links measures of frailty to trauma outcomes will be
      critical to informing future directions and health policy. The introduction of
      "Geriatric Emergency Departments" and the development of "Fracture Units" for
      frail older people will facilitate increased involvement of Geriatricians in
      trauma care and aid in the education of other health disciplines in the core
      principles of geriatric assessment and management. Collectively these should lead
      to improved care and outcomes for both survivors and those requiring end of life
      decisions and palliation. 

PMID- 26312121
TI  - Multiple Infectious Complications in a Severely Injured Patient with Single
      Nucleotide Polymorphisms in Important Innate Immune Response Genes.
AB  - Trauma is a major public health problem worldwide. Infectious complications,
      sepsis, and multiple organ dysfunction syndrome (MODS) remain important causes
      for morbidity and mortality in patients who survive the initial trauma. There is
      increasing evidence for the role of genetic variation in the innate immune system
      on infectious complications in severe trauma patients. We describe a trauma
      patient with multiple infectious complications caused by multiple micro-organisms
      leading to prolonged hospital stay with numerous treatments. This patient had
      multiple single nucleotide polymorphisms (SNPs) in the MBL2, MASP2, FCN2 and TLR2
      genes, most likely contributing to increased susceptibility and severity of
      infectious disease. 

PMID- 26312122
TI  - Traumatic Floating Knee: A Review of a Multi-Centric Series of 172 Cases in
      Adult.
AB  - The traumatic floating knee in adults (FK) is a combined injury of the lower limb
      defined by ipsilateral fractures of the tibia and femur. The first publications
      emphasized the severity of injuries, the bad results after conservative
      treatment, the most severe functional outcome in case of articular fracture and
      the frequency of associated cruciate ligament injuries. The surgical management
      of FK has been highly modified according the improvement of the fracture fixation
      devices and the operative techniques. This retrospective multicentric
      observational study included 172 adults with a FK injury admitted in emergency in
      5 different level I or II trauma centers. All the patients data were collected on
      an anonymized database. Results were evaluated by the overall clinical
      Karlstrom's score at latest follow-up. Fracture union was assessed on X-rays when
      at least 3 out of 4 cortices were in continuity in two different radiological
      planes. A statistical analysis was performed by a logistic regression method.
      Despite some limitations, this study confirms the general and local severity of
      this high-energy trauma, mainly occurring in young people around the third
      decade. A special effort should lead to a better initial diagnosis of associated
      ligamentous injury: a tear of PCL can be suspected on a lateral-ray view and a
      testing of the knee should be systematically performed after fixation of the
      fracture under anesthesia. Secondary MRI assessment is sometimes difficult to
      interpret because of hardware artifacts. The timing of fracture fixation is
      discussed on a case by case basis. However, a first femoral fixation is
      recommended except in cases of tibia fracture with major soft tissue lesion or
      leg ischemia requiring the tibia fixation first. Also a tibia stabilized
      facilitates the reduction and fixation of a complex distal femur fracture. The
      dual nailing remains so far for us the best treatment in Fraser I FK. Further
      prospective studies are needed to validate treatment algorithms, best fixation
      techniques in order to decrease the rate of complication and improve the
      functional outcome of floating knee injuries. 

PMID- 26312123
TI  - Visual Acuity, Contrast Sensitivity and Color Vision Three Years After Iodine-125
      Brachytherapy for Choroidal and Ciliary Body Melanoma.
AB  - PURPOSE: To report visual acuity, contrast sensitivity and color vision prior to,
      1 year after, 2 years after and 3 years after iodine-125 brachytherapy for
      choroidal and ciliary body melanoma (CCM). DESIGN: Prospective interventional
      case series. PARTICIPANTS: Thirty-seven patients (37 eyes) with CCM. METHODS:
      Patients had best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS)
      visual acuity, Pelli-Robson contrast sensitivity and Hardy-Rand-Rittler color
      vision measurement; comprehensive ophthalmology examination; optical coherence
      tomography; and ultrasonography at baseline prior to, 1 year after, 2 years after
      and 3 years after I-125 brachytherapy. MAIN OUTCOME MEASURES: Visual acuity,
      contrast sensitivity and color vision prior to, 1 year after, 2 years after and 3
      years after brachytherapy. RESULTS: Nineteen (19) men and 18 women with mean age
      of 58 years (SD 13, range 30-78) prior to, 1 year after, 2 years after and 3
      years after brachytherapy had mean best-corrected visual acuity of 77 letters
      (20/32), 65 letters (20/50), 56 letters (20/80) and 47 letters (20/125); contrast
      sensitivity of 30, 26, 22 and 19 letters; color vision of 26, 20, 17 and 14 test
      figures, respectively. Decrease in visual acuity, contrast sensitivity and color
      vision was statistically significant from baseline at 1 year, 2 years, and 3
      years after brachytherapy. Decreased acuity at 3 years was associated with mid
      choroid and macula melanoma location, >= 4.1 mm melanoma height, radiation
      maculopathy and radiation optic neuropathy. CONCLUSION: 1, 2 and 3 years after
      brachytherapy, eyes with CCM had significantly decreased visual acuity, contrast
      sensitivity and color vision.

PMID- 26312124
TI  - Self-Reorientation Following Colorectal Cancer Treatment - A Grounded Theory
      Study.
AB  - After colorectal cancer (CRC) treatment, people reorganize life in ways that are
      consistent with their understanding of the illness and their expectations for
      recovery. Incapacities and abilities that have been lost can initiate a need to
      reorient the self. To the best of our knowledge, no studies have explicitly
      focused on the concept of self-reorientation after CRC treatment. The aim of the
      present study was therefore to explore self-reorientation in the early recovery
      phase after CRC surgery. Grounded theory analysis was undertaken, using the
      method presented by Charmaz. The present results explained self-reorientation as
      the individual attempting to achieve congruence in self-perception. A congruent
      self-perception meant bringing together the perceived self and the self that was
      mirrored in the near environs. The results showed that societal beliefs and
      personal explanations are essential elements of self-reorientation, and that it
      is therefore important to make them visible. 

PMID- 26312126
TI  - Effects of environment on human cytokine responses during childhood in the
      tropics: role of urban versus rural residence.
AB  - BACKGROUND: Environment may have a key role in the development of the immune
      system in childhood and environmental exposures associated with rural residence
      may explain the low prevalence of allergic and autoimmune diseases in the rural
      tropics. We investigated the effects of urban versus rural residence on the
      adaptive immune response in children living in urban and rural areas in a
      tropical region of Latin America. METHODS: We recruited school children in either
      rural communities in the Province of Esmeraldas or in urban neighborhoods in the
      city of Esmeraldas, Ecuador. We collected data on environmental exposures by
      questionnaire and on intestinal parasites by examination of stool samples.
      Peripheral blood leukocytes (PBLs) in whole blood were stimulated with
      superantigen, parasite antigens and aeroallergens and IFN-gamma, IL-5, IL-10, IL
      13, and IL-17 were measured in supernatants. RESULTS: We evaluated 440 school
      children; 210 living in rural communities and 230 in the city of Esmeraldas.
      Overall, urban children had greater access to piped water (urban 98.7 % vs. rural
      1.9 %), were more likely to have a household bathroom (urban 97.4 % vs. rural
      54.8 %), and were less likely to be infected with soil-transmitted helminth
      infections (urban 20.9 % vs. rural 73.5 %). Generally, detectable levels of
      cytokines were more frequent in blood from children living in urban than rural
      areas. Urban residence was associated with a significantly greater frequency of
      IL-10 production spontaneously (adjusted OR 2.56, 95 % CI 1.05-6.24) and on
      stimulation with Ascaris (adj. OR 2.5, 95 % CI 1.09-5.79) and house dust mite
      (adj. 2.24, 95 % CI 1.07-4.70) antigens. Analysis of effects of environmental
      exposures on SEB-induced IL-10 production within urban and rural populations
      showed that some environmental exposures indicative of poor hygiene (urban -
      higher birth order, A. lumbricoides infection; rural - no bathroom, more peri
      domiciliary animals, and living in a wood/bamboo house) were associated with
      elevated IL-10. CONCLUSIONS: In our study population, the immune response of
      children living in an urban environment was associated more frequently with the
      production of the immune regulatory cytokine, IL-10. Some factors related to poor
      hygiene and living conditions were associated with elevated IL-10 production
      within urban and rural populations.

PMID- 26312127
TI  - Consensus communication on early peanut introduction and the prevention of peanut
      allergy in high-risk infants.
AB  - The purpose of this brief communication is to highlight emerging evidence to
      existing guidelines regarding potential benefits of supporting early, rather than
      delayed, peanut introduction during the period of complementary food introduction
      in infants. This document should be considered as interim guidance based on
      consensus among the following organizations: American Academy of Allergy, Asthma
      & Immunology; American Academy of Pediatrics; American College of Allergy, Asthma
      & Immunology; Australasian Society of Clinical Immunology and Allergy; Canadian
      Society of Allergy and Clinical Immunology; European Academy of Allergy and
      Clinical Immunology; Israel Association of Allergy and Clinical Immunology;
      Japanese Society for Allergology; Society for Pediatric Dermatology; and World
      Allergy Organization. More formal guidelines regarding early-life, complementary
      feeding practices and the risk of allergy development will follow in the next
      year from the National Institute of Allergy and Infectious Diseases - sponsored
      Working Group and the European Academy of Allergy and Clinical Immunology. 

PMID- 26312128
TI  - Karyotype characteristics and polymorphism peculiarities of Chironomusbernensis
      Wulker & Klotzli, 1973 (Diptera, Chironomidae) from the Central Caucasus and
      Ciscaucasia.
AB  - Data about the karyotype characteristics, features of chromosomal polymorphism
      and larval morphology of populations of Chironomusbernensis Wulker & Klotzli,
      1973 (Diptera, Chironomidae) from the Central Caucasus (the northern macroslope)
      and Ciscaucasia are presented. The characteristics of the pericentromeric regions
      of the long chromosomes of this species from Caucasian populations were very
      similar to the ones from some European populations (from Poland and Italy), but
      differed from Swiss and Siberian populations. In the North Caucasian populations
      10 banding sequences were found: two in arms A, C, and E, and one in arms B, D,
      F, and G. Nine of them were already known for this species, and one, berC2, is
      described for the first time. Cytogenetic distances between all the studied
      populations of Chironomusbernensis show that close geographical location of all
      studied populations from the Central Caucasus and Ciscaucasia is reflected in
      their similar cytogenetic structure, but on the other hand, that they are more
      closely related to populations from Europe than to populations from Western
      Siberia. At the same time, all studied larvae from Caucasian populations have a
      four-bladed premandible, instead of a two-bladed one, as in the description of
      Chironomusbernensis from Switzerland (Wulker and Klotzli 1973, Polukonova 2005c).
      These peculiarities may indicate the relative isolation of the Caucasus from the
      viewpoint of microevolution. Further research on karyological and morphological
      characteristics of Chironomusbernensis from geographically distant regions is
      necessary as there is a possibility that the presently known species is actually
      polytypic and consists of several sibling species. 

PMID- 26312125
TI  - Ultrahigh field MRI in clinical neuroimmunology: a potential contribution to
      improved diagnostics and personalised disease management.
AB  - Conventional magnetic resonance imaging (MRI) at 1.5 Tesla (T) is limited by
      modest spatial resolution and signal-to-noise ratio (SNR), impeding the
      identification and classification of inflammatory central nervous system changes
      in current clinical practice. Gaining from enhanced susceptibility effects and
      improved SNR, ultrahigh field MRI at 7 T depicts inflammatory brain lesions in
      great detail. This review summarises recent reports on 7 T MRI in
      neuroinflammatory diseases and addresses the question as to whether ultrahigh
      field MRI may eventually improve clinical decision-making and personalised
      disease management. 

PMID- 26312129
TI  - Genetic integrity of four species of Leptidea (Pieridae, Lepidoptera) as sampled
      in sympatry in West Siberia.
AB  - In southern West Siberia, as many as four Leptidea Billberg, 1820 species are
      present sympatrically: Leptideaamurensis (Menetries, 1859), Leptideamorsei
      (Menetries, 1859), Leptideasinapis (Linnaeus, 1758) and Leptideajuvernica
      Williams, 1946. The two latter were recently recognised as nearly sibling species
      on morphological and molecular characters. Specimens intermediate as to their
      subtle diagnostic characters occurring in West Siberia and elsewhere were
      interpreted as resulted from limited introgression. This supposition was tested
      via populational morphological and molecular analysis of spring brood specimens
      of all the four species taken from a limited (4.5 * 0.2 km) area in the suburbs
      of Novosibirsk. The samples were analysed with respect to the genitalic
      morphology, external characters, three nuclear (CAD, H1 gene and ITS2) and one
      mitochondrial (COI) molecular markers, infection of the intracellular maternally
      inherited bacterial symbiont Wolbachia Hertig, 1836 and its wsp gene coding for a
      hypervariable surface protein. Interspecific variation of the nuclear CAD and
      ITS2 sequences and the mitochondrial COI gene in Leptideasinapis and
      Leptideajuvernica turned out concordant. The absence of molecular evidence of
      introgression suggests genetic integrity of these two species and allows their
      reliable identification by molecular characters. The genitalic (lengths of the
      saccus and valva) and external characters (wing pattern) of males overlap in
      Leptideasinapis and Leptideajuvernica, as identified by molecular markers and
      thus are not so helpful in actual species identification. Only the ductus bursae
      length showed no overlap and can be used for identification of females. The
      histone H1 gene appeared five times less variable over the four studied species
      than COI, and found to be identical in species Leptideasinapis and
      Leptideajuvernica. Wolbachia infection was found in all studied species. We
      identified three wsp variants of Wolbachia: 1) wsp-10 allele in
      Leptideaamurensis, Leptideasinapis, Leptideajuvernica; 2) a very similar wsp-687
      allele in Leptideasinapis; and 3) wsp-688, highly divergent to the previous ones,
      in Leptideamorsei. 

PMID- 26312131
TI  - Molecular cytogenetic studies in the ladybird beetle Henosepilachnaargus
      Geoffroy, 1762 (Coleoptera, Coccinellidae, Epilachninae).
AB  - The ladybird Henosepilachnaargus Geoffroy, 1762 has been cytogenetically studied.
      In addition we have conducted a review of chromosome numbers and the chromosomal
      system of sex determination available in the literature in species belonging to
      the genus Henosepilachna and in its closely related genus Epilachna. Chromosome
      number of Henosepilachnaargus was 2n=18, including the sex chromosome pair, a
      common diploid chromosome number within the tribe Epilachnini. The study of
      prophase I meiotic chromosomes showed the typical Xyp "parachute" bivalent as in
      the majority of species of Coccinellidae. C-banding and fluorescent staining with
      AT-specific DAPI fluorochrome dye have been carried out for the first time in H.
      argus. C-banding technique revealed that heterochromatic blocks are
      pericentromerically located and DAPI staining showed that this heterochromatin is
      AT rich. Fluorescence in situ hybridizations using rDNA and the telomeric TTAGG
      sequence as probes have been carried out. FISH using rDNA showed that the
      nucleolar organizing region is located on the short arm of the X chromosome. FISH
      with the telomeric sequence revealed that in this species telomeres of
      chromosomes are composed of the pentanucleotide TTAGG repeats. This is the first
      study on the telomeric sequences in Coccinellidae. 

PMID- 26312130
TI  - General trends of chromosomal evolution in Aphidococca (Insecta, Homoptera,
      Aphidinea + Coccinea).
AB  - Parallel trends of chromosomal evolution in Aphidococca are discussed, based on
      the catalogue of chromosomal numbers and genetic systems of scale insects by
      Gavrilov (2007) and the new catalogue for aphids provided in the present paper.
      To date chromosome numbers have been reported for 482 species of scale insects
      and for 1039 species of aphids, thus respectively comprising about 6% and 24% of
      the total number of species. Such characters as low modal numbers of chromosomes,
      heterochromatinization of part of chromosomes, production of only two sperm
      instead of four from each primary spermatocyte, physiological sex determination,
      "larval" meiosis, wide distribution of parthenogenesis and chromosomal races are
      considered as a result of homologous parallel changes of the initial genotype of
      Aphidococca ancestors. From a cytogenetic point of view, these characters
      separate Aphidococca from all other groups of Paraneoptera insects and in this
      sense can be considered as additional taxonomic characters. In contrast to
      available paleontological data the authors doubt that Coccinea with their very
      diverse (and partly primitive) genetic systems may have originated later then
      Aphidinea with their very specialised and unified genetic system. 

PMID- 26312132
TI  - Spreading of heterochromatin and karyotype differentiation in two Tropidacris
      Scudder, 1869 species (Orthoptera, Romaleidae).
AB  - Tropidacris Scudder, 1869 is a genus widely distributed throughout the
      Neotropical region where speciation was probably promoted by forest reduction
      during the glacial and interglacial periods. There are no cytogenetic studies of
      Tropidacris, and information allowing inference or confirmation of the
      evolutionary events involved in speciation within the group is insufficient. In
      this paper, we used cytogenetic markers in two species, Tropidacriscollaris
      (Stoll, 1813) and Tropidacriscristatagrandis (Thunberg, 1824), collected in
      different Brazilian biomes. Both species exhibited 2n=24,XX for females and
      2n=23,X0 for males. All chromosomes were acrocentric. There were some differences
      in the karyotype macrostructure, e.g. in the chromosome size. A wide
      interspecific variation in the chromosome banding (C-banding and CMA3/DAPI
      staining) indicated strong differences in the distribution of repetitive DNA
      sequences. Specifically, Tropidacriscristatagrandis had a higher number of bands
      in relation to Tropidacriscollaris. FISH with 18S rDNA revealed two markings
      coinciding with the NORs in both species. However, two analyzed samples of
      Tropidacriscollaris revealed a heterozygous condition for the rDNA site of S10
      pair. In Tropidacriscollaris, the histone H3 genes were distributed on three
      chromosome pairs, whereas in Tropidacriscristatagrandis, these genes were
      observed on 14 autosomes and on the X chromosome, always in terminal regions. Our
      results demonstrate that, although the chromosome number and morphology are
      conserved in the genus, Tropidacriscristatagrandis substantially differs from
      Tropidacriscollaris in terms of the distribution of repetitive sequences. The
      devastation and fragmentation of the Brazilian rainforest may have led to
      isolation between these species, and the spreading of these repetitive sequences
      could contribute to speciation within the genus. 

PMID- 26312133
TI  - Contributions to cytogenetics of Plectranthusbarbatus Andr. (Lamiaceae): a
      medicinal plant.
AB  - Accessions of Plectranthusbarbatus (Lamiaceae), a medicinal plant, were
      investigated using a cytogenetic approach and flow cytometry (FCM). Here, we
      describe for the first time details of the karyotype including chromosome
      morphology, physical mapping of GC rich bands (CMA3 banding), as well as the
      mapping of 45S and 5S rDNA sites. All accessions studied showed karyotypes with
      2n = 30 small metacentric and submetacentric chromosomes. The CMA3 banding and
      fluorescent in situ hybridization techniques revealed coincidence between CMA3
      bands and 45S rDNA sites (6 terminal marks) while for the 5S rDNA were observed 4
      subterminal marks no coincident with CMA3 marks. For nuclear genome size
      measurement, the FCM procedure provided histograms with G0/G1 peaks exhibiting CV
      between 2.0-4.9 and the mean values obtained for the species was 2C = 2.78 pg,
      with AT% = 61.08 and GC% = 38.92. The cytogenetic data obtained here present new
      and important information which enables the characterization of
      Plectranthusbarbatus. 

PMID- 26312134
TI  - The actinin family of actin cross-linking proteins - a genetic perspective.
AB  - Actinins are one of the major actin cross-linking proteins found in virtually all
      cell types and are the ancestral proteins of a larger family that includes
      spectrin, dystrophin and utrophin. Invertebrates have a single actinin-encoding
      ACTN gene, while mammals have four. Mutations in all four human genes have now
      been linked to heritable diseases or traits. ACTN1 mutations cause
      macrothrombocytopenia, a platelet disorder characterized by excessive bleeding.
      ACTN2 mutations have been linked to a range of cardiomyopathies, and ACTN4
      mutations cause a kidney condition called focal segmental glomerulosclerosis.
      Intriguingly, approximately 16 % of people worldwide are homozygous for a
      nonsense mutation in ACTN3 that abolishes actinin-3 protein expression. This
      ACTN3 null allele has undergone recent positive selection in specific human
      populations, which may be linked to improved endurance and adaptation to colder
      climates. In this review we discuss the human genetics of the ACTN gene family,
      as well as ACTN gene knockout studies in several model organisms. Observations
      from both of these areas provide insights into the evolution and cellular
      functions of actinins. 

PMID- 26312135
TI  - A physical association between the human mutY homolog (hMYH) and DNA
      topoisomerase II-binding protein 1 (hTopBP1) regulates Chk1-induced cell cycle
      arrest in HEK293 cells.
AB  - BACKGROUND: Human DNA topoisomerase II-binding protein 1 (hTopBP1) plays an
      important role in DNA replication and the DNA damage checkpoint pathway. The
      human mutY homolog (hMYH) is a base excision repair DNA glycosylase that excises
      adenines or 2-hydroxyadenines that are mispaired with guanine or 7,8-dihydro-8
      oxoguanine (8-oxoG). hTopBP1 and hMYH were involved in ATR-mediated Chk1
      activation, moreover, both of them were associated with ATR and hRad9 which known
      as checkpoint-involved proteins. Therefore, we investigated whether hTopBP1
      interacted with hMYH, and what the function of their interaction is. RESULTS: We
      documented the interaction between hTopBP1 and hMYH and showed that this
      interaction increased in a hydroxyurea-dependent manner. We also mapped the hMYH
      interacting region of hTopBP1 (residues 444-991). In addition, we investigated
      several cell cycle-related proteins and found that co-knockdown of hTopBP1 and
      hMYH significantly diminished cell cycle arrest due to compromised checkpoint
      kinase 1 (Chk1) activation. Moreover, we observed that hMYH was essential for the
      accumulation of hTopBP1 on damaged DNA, where hTopBP1 interacts with hRad9, a
      component of the Rad9-Hus1-Rad1 complex. The accumulation of hTopBP1 on chromatin
      and its subsequent interaction with hRad9 lead to cell cycle arrest, a process
      mediated by Chk1 phosphorylation and ataxia telangiectasia and Rad3-related
      protein (ATR) activation. CONCLUSIONS: Our results suggested that hMYH is
      necessary for the accumulation of hTopBP1 to DNA damage lesion to induce the
      association of hTopBP1 with 9-1-1 and that the interaction between hMYH and
      hTopBP1 is essential for Chk1 activation. Therefore, we suggest that the
      interaction between hMYH and hTopBP1 is crucial for activation of the ATR
      mediated cell cycle checkpoint.

PMID- 26312136
TI  - Large Deflection Shape Sensing of a Continuum Manipulator for Minimally-Invasive
      Surgery.
AB  - Shape sensing techniques utilizing Fiber Bragg grating (FBG) arrays can enable
      real-time tracking and control of dexterous continuum manipulators (DCM) used in
      minimally invasive surgeries. For many surgical applications, the DCM may need to
      operate with much larger curvatures than what current shape sensing methods can
      detect. This paper proposes a novel shape sensor, which can detect a radius of
      curvature of 15 mm for a 35 mm long DCM. For this purpose, we used FBG sensors
      along with nitinol wires as the supporting substrates to form a triangular cross
      section. For verification, we assembled the sensor inside the wall of the DCM.
      Experimental results indicate that the proposed sensor can detect the DCM's
      curvature with an average error of 3.14%.

PMID- 26312137
TI  - Novel Method to Improve Radiologist Agreement in Interpretation of Serial Chest
      Radiographs in the ICU.
AB  - OBJECTIVES: To determine whether a novel method and device, called a variable
      attenuation plate (VAP), which equalizes chest radiographic appearance and allows
      for synchronization of manual image windowing with comparison studies, would
      improve consistency in interpretation. MATERIALS AND METHODS: Research ethics
      board approved the prospective cohort pilot study, which included 50 patients in
      the intensive care unit (ICU) undergoing two serial chest radiographs with a VAP
      placed on each one of them. The VAP allowed for equalization of density and
      contrast between the patients' serial chest radiographs. Three radiologists
      interpreted all the studies with and without the use of VAP. Kappa and percent
      agreement was used to calculate agreement between radiologists' interpretations
      with and without the plate. RESULTS: Radiologist agreement was substantially
      higher with the VAP method, as compared to that with the non-VAP method. Kappa
      values between Radiologists A and B, A and C, and B and C were 46%, 55%, and 51%,
      respectively, which improved to 73%, 81%, and 66%, respectively, with the use of
      VAP. Discrepant report impressions (i.e., one radiologist's impression of
      unchanged versus one or both of the other radiologists stating improved or
      worsened in their impression) ranged from 24 to 28.6% without the use of VAP and
      from 10 to 16% with the use of VAP (chi (2) = 7.454, P < 0.01). Opposing views
      (i.e., one radiologist's impression of improved and one of the others stating
      disease progression or vice versa) were reported in 7 (12%) cases in the non-VAP
      group and 4 (7%) cases in the VAP group (chi (2) = 0.85, P = 0.54). CONCLUSION:
      Numerous factors play a role in image acquisition and image quality, which can
      contribute to poor consistency and reliability of portable chest radiographic
      interpretations. Radiologists' agreement of image interpretation can be improved
      by use of a novel method consisting of a VAP and associated software and has the
      potential to improve patient care.

PMID- 26312138
TI  - Corticosteroid Responsive Sarcoidosis with Multisystemic Involvement Years after
      Initial Diagnosis: A Lymphoma Mimicker on 18-FDG PET/CT.
AB  - Sarcoidosis is a chronic multisystemic inflammatory disease characterized by
      noncaseating epithelioid cell granulomas. 18-Fluorodeoxyglucose positron-emission
      tomography/computer tomography (FDG-PET/CT) is increasingly used in routine
      clinical practice to assess active sarcoidosis because it can detect active
      inflammatory granulomatous disease. However, active sarcoidosis lesions are
      observed to be hypermetabolic on FDG-PET/CT much like malignancies, which may
      lead to misinterpretation on imaging. In this case report, we present a rare case
      of sarcoidosis with multisystem involvement including lung, lymph nodes, bone,
      pleura, and soft tissue that mimicked lymphoma on FDG-PET/CT and responded to
      corticosteroid treatment. 

PMID- 26312139
TI  - Pilomyxoid Astrocytoma Occurring in the Third Ventricle.
AB  - Pilomyxoid astrocytoma (PMA) is a rare central nervous system tumor that has been
      included in the 2007 World Health Organization Classification of Tumors of the
      Central Nervous System. Due to its more aggressive behavior, PMA is classified as
      Grade II neoplasm by the World Health Organization. PMA predominantly affects the
      hypothalamic/chiasmatic region and occurs in children (mean age of occurrence =
      10 months). We report a case of a 24-year-old man who presented with headache,
      nausea, and vomiting. Brain CT and MRI revealed a mass occupying only the third
      ventricle. We performed partial resection. Histological findings, including
      monophasic growth with a myxoid background, and absence of Rosenthal fibers or
      eosinophilic granular bodies, as well as the strong positivity for glial
      fibrillary acidic protein were consistent with PMA. 

PMID- 26312140
TI  - Sonographic Hair-on-end Sign in Osteosarcoma.
AB  - This report is a case of osteosarcoma in a young female whose initial examination
      was sonography. This examination demonstrated a femoral tumor and included a
      unique finding corresponding to the radiographic hair-on-end sign of malignant
      new bone formation. 

PMID- 26312141
TI  - Back to Basics - 'Must Know' Classical Signs in Thoracic Radiology.
AB  - There are a few signs in radiology which are based on many common objects or
      patterns that we come across in our routine lives. The objective behind the
      association between such common objects and the corresponding pathologies is to
      make the reader understand and remember the disease process. These signs do not
      necessarily indicate a particular disease, but are usually suggestive of a group
      of similar pathologies which will facilitate in the narrowing down of the
      differential diagnosis. These signs can be seen in different imaging modalities
      like plain radiograph and computed tomography. In this essay, we describe 24
      classical radiological signs used in chest imaging, which would be extremely
      helpful in routine clinical practice not only for radiologists but also for chest
      physicians and cardiothoracic surgeons. 

PMID- 26312143
TI  - New insights into the pathogenesis and therapeutics of kidney fibrosis.

PMID- 26312142
TI  - Pulmonary Tumor Thrombotic Microangiopathy: Clinical, Radiologic, and Histologic
      Correlation.
AB  - Pulmonary tumor thrombotic microangiopathy (PTTM) is a clinicopathologic disease
      entity in which the tumor cells embolize to the pulmonary vasculature leading to
      a series of maladaptive reactions including the activation of coagulation and
      fibrocellular intimal thickening. The resultant stenosis of blood vessels leads
      to pulmonary hypertension and eventual death from cor pulmonale. In this report,
      we present a case of PTTM presenting as the initial manifestation of metastatic
      gastric carcinoma in a young man. Although unusual in its occurrence as the
      initial manifestation of gastric carcinoma, the case is illustrative in its
      clinical, radiological and histological presentation. 

PMID- 26312145
TI  - Macrophage heterogeneity, phenotypes, and roles in renal fibrosis.
AB  - Macrophages (MPhi) are highly heterogeneous cells that exhibit distinct
      phenotypic and functional characteristics depending on their microenvironment and
      the disease type and stage. MPhi are distributed throughout normal and diseased
      kidney tissue, where they have been recognized as key factors in renal fibrosis.
      Recent studies have identified switch of phenotype and diverse roles for MPhi in
      several murine models of kidney disease. In this review, we discuss macrophage
      heterogeneity and their involvement in renal fibrosis.

PMID- 26312144
TI  - What is the best way to measure renal fibrosis?: A pathologist's perspective.
AB  - Interstitial fibrosis is a hallmark structural correlate of progressive and
      chronic kidney disease. There remain many uncertainties about how to best measure
      interstitial fibrosis both in research settings and in evaluations of renal
      biopsies performed for management of individual patients. Areas of uncertainty
      include determination of the composition of the matrix in a fibrotic parenchyma,
      the definition of how the interstitium is involved by fibrosing injuries, the
      choice of histologic stains for evaluation of renal fibrosis, and the
      reproducibility and robustness of measures currently employed by pathologists,
      both with and without the assistance of computerized imaging and assessments. In
      this review, we address some of these issues while citing the key studies that
      illustrate these difficulties. We point to future approaches that may allow a
      more accurate and meaningful assessment of renal interstitial fibrosis.

PMID- 26312146
TI  - Toll-like receptor activation: from renal inflammation to fibrosis.
AB  - Toll-like receptors (TLRs) are a conserved family of pattern recognition
      receptors that play a fundamental role in the innate immune system by triggering
      proinflammatory signaling pathways in response to microbial pathogens through
      exogenous pathogen-associated molecular patterns or tissue injury through
      endogenous danger-associated molecular patterns. In the kidney, TLRs are widely
      expressed in a variety of cell types. Emerging evidence demonstrates the
      participation of TLRs in the activation of these cells during renal fibrosis.
      This review highlights the role of TLRs and their endogenous ligands in the
      pathogenesis of renal fibrosis using ureteral obstruction and diabetic
      nephropathy as models of chronic kidney disease.

PMID- 26312147
TI  - The FOXD1 lineage of kidney perivascular cells and myofibroblasts: functions and
      responses to injury.
AB  - Recent studies have identified a poorly appreciated yet extensive population of
      perivascular mesenchymal cells in the kidney, which are derived from metanephric
      mesenchyme progenitor cells during nephrogenesis at which time they express the
      transcription factor FOXD1. Some studies have called these resident fibroblasts,
      whereas others have called them pericytes. Regardless of nomenclature, many are
      partially integrated into the capillary basement membrane and contribute in
      important ways to the homeostasis of peritubular capillaries. Fate-mapping
      studies using conditional CreER recombinase-mediated tracing of discrete cell
      cohorts have identified these pericytes and resident fibroblasts as the major
      precursor population of interstitial myofibroblasts in animal models of kidney
      disease. Here, we will review the evidence that they are the major population of
      myofibroblast precursors, highlight some critical functions in homeostasis, and
      focus on the cell signaling pathways that are important to their differentiation
      into, and persistence as myofibroblasts.

PMID- 26312148
TI  - Macrophages promote renal fibrosis through direct and indirect mechanisms.
AB  - There is a close spatial and temporal relationship between macrophage
      accumulation and active renal fibrosis in human and experimental kidney disease.
      Different subtypes of macrophages have been identified. Pro-inflammatory M1-type
      macrophages can cause acute tissue injury, whereas pro-fibrotic M2-type
      macrophages can drive the fibrotic response during ongoing tissue injury.
      Macrophages induce fibrosis through the recruitment, proliferation, and
      activation of fibroblasts. In addition, there is accumulating evidence that
      supports a direct fibrotic role for macrophages via transition into
      myofibroblasts in a process termed macrophage-myofibroblast transition (MMT). Co
      expression of macrophage and myofibroblast antigens identifies the MMT process
      both in human and experimental fibrotic kidney disease. This co-expression
      identifies a bone marrow-derived monocyte/macrophage source for a substantial
      proportion of the myofibroblast population present during renal fibrosis. This
      postulated MMT pathway represents a new mechanism linking macrophage-rich acute
      inflammation with the progression to myofibroblast accumulation and renal
      fibrosis. Further studies are required to identify the molecular mechanisms
      regulating the MMT process, which macrophage populations can undergo MMT, and to
      define the functional contribution of MMT to active collagen deposition during
      renal fibrosis.

PMID- 26312149
TI  - Tipping the balance from angiogenesis to fibrosis in CKD.
AB  - Chronic progressive renal fibrosis leads to end-stage renal failure many patients
      with chronic kidney disease (CKD). Loss of the rich peritubular capillary network
      is a prominent feature, and seems independent of the specific underlying disease.
      The mechanisms that contribute to peritubular capillary regression include the
      loss of glomerular perfusion, as flow-dependent shear forces are required to
      provide the survival signal for endothelial cells. Also, reduced endothelial cell
      survival signals from sclerotic glomeruli and atrophic or injured tubule
      epithelial cells contribute to peritubular capillary regression. In response to
      direct tubular epithelial cell injury, and the inflammatory reaction that ensues,
      capillary pericytes dissociate from their blood vessels, also reducing
      endothelial cell survival. In addition, direct inflammatory injury of capillary
      endothelial cells, for instance in chronic allograft nephropathy, also
      contributes to capillary dropout. Chronic tissue hypoxia, which ensues from the
      rarefaction of the peritubular capillary network, can generate both an angiogenic
      and a fibrogenic response. However, in CKD, the balance is strongly tipped toward
      fibrogenesis. Understanding the underlying mechanisms for failed angiogenesis in
      CKD and harnessing endothelial-specific survival and pro-angiogenic mechanisms
      for therapy should be our goal if we are to reduce the disease burden from CKD.

PMID- 26312150
TI  - Searching novel diagnostic markers and targets for therapy of CKD.
AB  - Over the last decade, identification and characterization of novel markers of
      progression and targets for therapy of chronic kidney disease (CKD) have been
      challenging for the research community. Several promising candidates have
      emerged, mainly from experimental models of CKD that are yet to be investigated
      in clinical studies. The authors identified two candidate genes: periostin, an
      extracellular matrix protein involved in bone and dental development, and the
      discoidin domain receptor 1 (DDR1), a collagen-binding membrane receptor with
      tyrosine kinase activity. Both genes are inactive in adulthood under normal
      conditions but have been shown to be highly inducible following injury to
      glomerular or tubular epithelial cells. The objective of this review is to
      summarize recent evidence supporting the role of periostin and DDR1 as potential
      novel biomarkers and therapeutic targets in CKD.

PMID- 26312151
TI  - Key fibrogenic mediators: old players. Renin-angiotensin system.
AB  - Interstitial fibrosis represents the final common pathway of any form of
      progressive renal disease. The severity of tubular interstitial damage is highly
      correlated to the degree of decline of renal function, even better than the
      glomerular lesions do. Angiotensin II (Ang II), the main effector of the renin
      angiotensin system, is a critical promoter of fibrogenesis. It represents a nexus
      among glomerular capillary hypertension, barrier dysfunction, and renal tubular
      injury caused by abnormally filtered proteins. Transforming growth factor (TGF)
      beta1 and reactive oxygen species (ROS) are the key mediators of the pro-fibrotic
      effect of Ang II causing apoptosis and epithelial-to-mesenchymal transition of
      the renal tubular epithelium. Recent studies link fibrosis to changes of microRNA
      (miRNA) modulated by Ang II through TGF-beta1, unraveling that antifibrotic
      action of Ang II antagonism is attributable to epigenetic control of fibrosis
      associated genes. Other mechanisms of Ang II-induced fibrosis include ROS
      dependent activation of hypoxia-inducible factor-1. Finally, Ang II via
      angiotensin type 1 receptor regulates the activation and transdifferentiation of
      pericytes and fibrocytes into scar-forming myofibroblasts. Detachment and
      phenotypic changes of the former can lead to the loss of peritubular capillaries
      and also contribute to hypoxia-dependent fibrosis.

PMID- 26312152
TI  - Platelet-derived growth factors (PDGFs) in glomerular and tubulointerstitial
      fibrosis.
AB  - Renal fibrosis is the hallmark of chronic kidney disease progression and is
      characterized by an exaggerated wound-healing process with the production of
      renal scar tissue. It comprises both the glomerular and the tubulointerstitial
      compartments. Among the factors that contribute to kidney fibrosis, the members
      of the platelet-derived growth factor (PDGF) family are among the best
      characterized ones. They appear to be the key factors in driving renal fibrosis,
      independent of the underlying kidney disease. The PDGF family consists of four
      isoforms (PDGF-A, -B, -C, and -D) and two receptor chains (PDGFR-alpha and 
      beta), which are constitutively or inducibly expressed in most renal cells. These
      components have an irreplaceable role in kidney development by recruitment of
      mesenchymal cells to the glomerular and tubulointerstitial compartments. They
      further regulate multiple pathophysiologic processes including cell
      proliferation, cell migration, expression and accumulation of extracellular
      matrix, production and secretion of pro- and anti-inflammatory mediators,
      vascular permeability, and hemodynamics. This review provides a brief update on
      the role of different PDGF isoforms in the development of glomerulosclerosis and
      tubulointerstitial fibrosis, newly identified endogeneous PDGF antagonists, and
      resulting potential therapies.

PMID- 26312153
TI  - EGFR signaling in renal fibrosis.
AB  - Signaling through the epidermal growth factor receptor (EGFR) is involved in
      regulation of multiple biological processes, including proliferation, metabolism,
      differentiation, and survival. Owing to its aberrant expression in a variety of
      malignant tumors, EGFR has been recognized as a target in anticancer therapy.
      Increasingly, evidence from animal studies indicates that EGFR signaling is also
      implicated in the development and progression of renal fibrosis. The therapeutic
      value of EGFR inhibition has not yet been evaluated in human kidney disease. In
      this article, we summarize recent research into the role of EGFR signaling in
      renal fibrogenesis, discuss the mechanism by which EGFR regulates this process,
      and consider the potential of EGFR as an antifibrotic target.

PMID- 26312154
TI  - Fibrosis and renal aging.
AB  - Glomerulosclerosis and interstitial fibrosis increase in the aging kidney, and
      glomerular filtration rate (GFR) decreases with increasing age. Decreases in stem
      cell number and function contribute to renal aging. High-dose angiotensin
      receptor blocker (ARB) not only slows the progression of glomerular and vascular
      sclerosis in aging but can also induce regression of these processes
      independently of its hemodynamic actions. By using new interventions, such as
      peroxisome proliferator activator receptor gamma (PPARgamma) agonist, we can
      manipulate the process of renal aging by regulating stem cells and other
      mechanisms.

PMID- 26312155
TI  - Biomarkers in kidney fibrosis: are they useful?
AB  - With the escalating cost of monitoring and follow-up required in the care of
      patients with chronic kidney disease (CKD), biomarkers are increasingly being
      investigated for their utility in predicting patients most at risk of decline in
      renal function in order to rationalize and target care. Putative biomarkers have
      also emerged as treatment targets, with the potential to develop novel
      therapeutics. However, biomarker studies in CKD are largely derived from single
      sample collections in observational or nested case-control studies that are
      suboptimal in study design, analyses, and end points relevant to confirm the
      utility of specific biomarkers. It has been demonstrated that biomarker
      expression may be modified by declining kidney function. Hence, their value in
      predicting future kidney dysfunction is limited. Therefore, understanding the
      nature, mechanism of action, and how specific biomarkers interact with the CKD
      disease process is a crucial step in defining the potential for biomarkers to
      predict outcome, or alternatively, develop as a therapeutic target. Unlike
      conventional risk factors that, albeit partly, enable us to distinguish an
      individual at risk of cardiovascular disease, biomarkers in patients with CKD may
      not be required to be modifiable either directly or indirectly in the disease
      process or by therapy. Reproducibility and prospective validation remain major
      challenges for the burgeoning number of purported biomarkers in patients with
      CKD. It is highly likely a combination of conventional and novel biomarkers will
      be needed to accurately predict the risk of end-stage kidney disease. This review
      will focus on recently identified biomarkers and their utility in predicting
      progressive kidney fibrosis.

PMID- 26312156
TI  - Wnt/beta-catenin signaling and kidney fibrosis.
AB  - Wnt/beta-catenin signaling is an evolutionarily conserved, highly complex, key
      developmental pathway that regulates cell fate, organ development, tissue
      homeostasis, as well as injury and repair. Although relatively silent in normal
      adult kidney, Wnt/beta-catenin signaling is re-activated after renal injury in a
      wide variety of animal models and in human kidney disorders. Whereas some data
      point to a protective role of this signaling in healing and repair after acute
      kidney injury, increasing evidence suggests that sustained activation of Wnt/beta
      catenin is associated with the development and progression of renal fibrotic
      lesions. In kidney cells, Wnt/beta-catenin promotes the expression of numerous
      fibrosis-related genes such as Snail1, plasminogen activator inhibitor-1, and
      matrix metalloproteinase-7. Recent studies also indicate that multiple components
      of the renin-angiotensin system are the direct downstream targets of Wnt/beta
      catenin. Consistently, inhibition of Wnt/beta-catenin signaling by an assortment
      of strategies ameliorates kidney injury and mitigates renal fibrotic lesions in
      various models of chronic kidney disease, suggesting that targeting this
      signaling could be a plausible strategy for therapeutic intervention. In this
      mini review, we will briefly discuss the regulation, downstream targets, and
      mechanisms of Wnt/beta-catenin signaling in the pathogenesis of kidney fibrosis.

PMID- 26312157
TI  - Kick it up a notch: Notch signaling and kidney fibrosis.
AB  - Notch is a critical regulator of kidney development, but the pathway is mostly
      silenced once kidney maturation is achieved. Recent reports demonstrated
      increased expression of Notch receptors and ligands both in acute and chronic
      kidney injury. In vivo studies indicated that Notch activation might contribute
      to regeneration after acute kidney injury; on the other hand, sustained Notch
      expression is causally associated with interstitial fibrosis and
      glomerulosclerosis. This review will summarize the current knowledge on the role
      of the Notch signaling with special focus on kidney fibrosis.

PMID- 26312158
TI  - Role of HIPK2 in kidney fibrosis.
AB  - Homeodomain interacting protein kinase 2 (HIPK2) functions as either a co
      repressor or a co-activator of transcriptional regulators. Dysregulation of HIPK2
      is associated with cancer and neurological disease. Recently, we found that HIPK2
      is also an important driver of kidney fibrosis in the HIV-1 transgenic murine
      model, Tg26. HIPK2 protein levels are upregulated in the tubular epithelial cells
      of Tg26 mice as well as in kidney biopsies of patients with HIV-associated
      nephropathy, focal segmental glomerulosclerosis, diabetic nephropathy, and IgA
      nephropathy. We found that HIPK2 regulates pro-apoptotic, pro-fibrotic, and pro
      inflammatory pathways including p53, transforming growth factor beta (TGF-beta)
      SMAD family member 3 (Smad3), Notch, Wingless and INT-1 (Wnt)/beta-catenin, and
      nuclear factor kappa-light-chain-enhancer of activated B cells in renal tubular
      epithelial cells. Our data suggest that HIPK2 may be a potential target for
      antifibrotic therapy. As mice with germline deletion of HIPK2 do not exhibit any
      phenotypic change under basal conditions, we do not expect significant side
      effects with specific HIPK2 inhibitors. However, potential effects of HIPK2 on
      tumor growth should be considered because of its tumor suppressor effects.
      Therefore, further understanding of structure-function relationships and post
      translational modifications of HIPK2 are necessary to develop more specific drugs
      targeting the pro-fibrotic effects of HIPK2.

PMID- 26312159
TI  - AOPPs and the progression of kidney disease.
AB  - Advanced oxidation protein products (AOPPs) are the dityrosine-containing and
      crosslinking protein products formed during oxidative stress by reaction of
      plasma protein with chlorinated oxidants, and often carried by albumin in vivo.
      Accumulation of plasma and renal AOPPs is a common pathologic finding in chronic
      kidney disease (CKD) patients. Moreover, AOPP accumulation is an independent risk
      factor for cardiovascular events (CVDs) in CKD. Clinical and experimental studies
      indicate that AOPPs are involved in the structural changes of progressive
      nephropathies such as glomerulosclerosis, interstitial fibrosis, and tubular
      atrophy via the redox-dependent pathway. Mounting evidence supports the role of
      AOPPs as a new class of renal pathogenic mediators in the progression of CKD.
      This mini review describes the formation of AOPPs, the involvement of AOPPs in
      CKD pathogenesis, and the underlying mechanisms.

PMID- 26312160
TI  - Therapeutic implications of intratumor heterogeneity for TP53 mutational status
      in Burkitt lymphoma.
AB  - Therapeutic implications of intra-tumor heterogeneity are still undefined. In
      this study we report a genetic and functional analysis aimed at defining the
      mechanisms of chemoresistance in a 43-year old woman affected by stage IVB
      Burkitt lymphoma with bulky abdominal masses and peritoneal effusion. The
      patient, despite a transient initial response to chemotherapy with reduction of
      the bulky masses, rapidly progressed and died of her disease. Targeted TP53
      sequencing found that the bulky mass was wild-type whereas peritoneal fluid cells
      harbored a R282W mutation. Functional studies on TP53 mutant cells demonstrated
      an impaired p53-mediated response, resistance to ex vivo doxorubicin
      administration, overexpression of DNA damage response (DDR) activation markers
      and high sensitivity to pharmacologic DDR inhibition. These findings suggest that
      intra-tumor heterogeneity for TP53 mutational status may occur in MYC-driven
      cancers, and that DDR inhibitors could be effective in targeting hidden TP53
      mutant clones in tumors characterized by genomic instability and prone to intra
      tumor heterogeneity. 

PMID- 26312161
TI  - Integrated Simulation Framework for Toxicity, Dose Intensity, Disease
      Progression, and Cost Effectiveness for Castration-Resistant Prostate Cancer
      Treatment With Eribulin.
AB  - Quantitative model-based analyses are helpful to support decision-making in drug
      development. In oncology, disease progression/clinical outcome (DPCO) models have
      been used for early predictions of clinical outcome, but most of such approaches
      did not include adverse events or dose intensity. In addition, cost-effectiveness
      evaluations of investigational compounds are becoming increasingly important.
      Here, we developed an integrated model-based framework including relevant
      treatment effects for patients with castration-resistant prostate cancer treated
      with the anticancer agent eribulin. The framework included (i) a DPCO model
      relating prostate-specific antigen (PSA) dynamics to survival; (ii) models for
      adverse events including dose-limiting neutropenia and other graded toxicities;
      (iii) a model for Eastern Cooperative Oncology Group (ECOG) performance score;
      (iv) a model for dropout; (v) the consideration of cost effectiveness. The model
      allowed simulation of realistic treatment courses. Subsequently, simulations
      evaluating alternative treatment protocols or patient characteristics were
      performed in order to derive inferences on expected efficacy and cost
      effectiveness. 

PMID- 26312162
TI  - Disease Progression/Clinical Outcome Model for Castration-Resistant Prostate
      Cancer in Patients Treated With Eribulin.
AB  - Frameworks that associate cancer dynamic disease progression models with
      parametric survival models for clinical outcome have recently been proposed to
      support decision making in early clinical development. Here we developed such a
      disease progression clinical outcome model for castration-resistant prostate
      cancer (CRPC) using historical phase II data of the anticancer agent eribulin.
      Disease progression was captured using the dynamics of prostate-specific antigen
      (PSA). For clinical outcome, overall survival (OS) was used. The model for PSA
      dynamics comprised parameters for baseline PSA (23.2 ng/ml, relative standard
      error (RSE) 16.5%), growth rate (0.00879 day(-1), RSE 12.6%), drug effect (0.241
      ug.h.l(-1) day(-1), RSE 32.6%), and resistance development (0.0113 day(-1), RSE
      44.3%). OS was modeled according to a Weibull distribution. Predictors for
      survival included model-predicted PSA time to nadir (TTN), PSA growth rate,
      Eastern Cooperative Oncology Group (ECOG) score, and baseline PSA. The developed
      framework can be considered to support informative design and analysis of drugs
      developed for CRPC. 

PMID- 26312163
TI  - Using a Systems Pharmacology Model of the Blood Coagulation Network to Predict
      the Effects of Various Therapies on Biomarkers.
AB  - A number of therapeutics have been developed or are under development aiming to
      modulate the coagulation network to treat various diseases. We used a systems
      model to better understand the effect of modulating various components on blood
      coagulation. A computational model of the coagulation network was built to match
      in-house in vitro thrombin generation and activated Partial Thromboplastin Time
      (aPTT) data with various concentrations of recombinant factor VIIa (FVIIa) or
      factor Xa added to normal human plasma or factor VIII-deficient plasma.
      Sensitivity analysis applied to the model revealed that lag time, peak thrombin
      concentration, area under the curve (AUC) of the thrombin generation profile, and
      aPTT show different sensitivity to changes in coagulation factors' concentrations
      and type of plasma used (normal or factor VIII-deficient). We also used the model
      to explore how variability in concentrations of the proteins in coagulation
      network can impact the response to FVIIa treatment. 

PMID- 26312164
TI  - Model-Based Once-Daily Darunavir/Ritonavir Dosing Recommendations in Pediatric
      HIV-1-Infected Patients Aged >=3 to <12 Years.
AB  - An existing population pharmacokinetic model of darunavir in adults was updated
      using pediatric data from two studies evaluating weight-based, once-daily dosing
      of darunavir/ritonavir (ARIEL, NCT00919854 and DIONE, NCT00915655). The model was
      then used to provide once-daily dosing recommendations for darunavir/ritonavir in
      pediatric patients aged >=3 to <12 years. The final model comprised two
      compartments with first-order absorption and apparent clearance dependent on the
      concentration of alpha1-acid glycoprotein. The recommended darunavir/ritonavir
      once-daily dosing regimens in children aged >=3 to <12 years are: 35/7 mg/kg from
      10 to <15 kg, 600/100 mg from 15 to <30 kg, 675/100 mg from 30 to <40 kg, and
      800/100 mg for >=40 kg. These doses should result in exposures similar to the
      adult exposure after treatment with darunavir/ritonavir 800/100 mg once daily,
      while minimizing pill burden and allowing a switch from suspension to tablet(s)
      as early as possible. 

PMID- 26312165
TI  - IDEA: Integrated Drug Expression Analysis-Integration of Gene Expression and
      Clinical Data for the Identification of Therapeutic Candidates.
AB  - Cancer drug discovery is an involved process spanning efforts from several fields
      of study and typically requires years of research and development. However, the
      advent of high-throughput genomic technologies has allowed for the use of in
      silico, genomics-based methods to screen drug libraries and accelerate drug
      discovery. Here we present a novel approach to computationally identify drug
      candidates for the treatment of breast cancer. In particular, we developed a Drug
      Regulatory Score similarity metric to evaluate gene expression profile
      similarity, in the context of drug treatment, and incorporated time-to-event
      patient survival information to develop an integrated analysis pipeline:
      Integrated Drug Expression Analysis (IDEA). We were able to predict drug
      candidates that have been known and those that have not been known in the
      literature to exhibit anticancer effects. Overall, our method enables quick
      preclinical screening of drug candidates for breast cancer and other diseases by
      using the most important indicator of drug efficacy: survival. 

PMID- 26312166
TI  - Relationships Between Pharmacovigilance, Molecular, Structural, and Pathway Data:
      Revealing Mechanisms for Immune-Mediated Drug-Induced Liver Injury.
AB  - Immune-mediated drug-induced liver injury (IMDILI) can be devastating,
      irreversible, and fatal in the absence of successful transplantation surgery. We
      present a novel approach that combines the methods of pharmacoepidemiology with
      in silico molecular modeling to identify specific features in toxic ligands that
      are associated with clinical features of IMDILI. Specifically, from
      pharmacovigilance data multivariate logistic regression identified 18 drugs
      associated with IMDILI (P < 0.00015). Eleven of these drugs, along with their
      known and proposed metabolites, constituted a training set used to develop a four
      point pharmacophore model (sensitivity 75%; specificity 85%). Subsequently, this
      information was combined with information from immune-pathway reviews and genetic
      association studies and complemented with ligand-protein docking simulations to
      support a hypothesis implicating two putative targets within separate, possibly
      interacting, immune-system pathways: the major histocompatibility complex within
      the adaptive immune system and Toll-like receptors (TLRs), in particular TLR-7,
      which represent pattern recognition receptors of the innate immune system. 

PMID- 26312168
TI  - Interactions between donor Agreeableness and recipient characteristics in
      predicting charitable donation and positive social evaluation.
AB  - Agreeable people are more likely to display prosocial attitudes and helpful
      behavior in a broad range of situations. Here we show that this tendency
      interacts with the personal characteristics of interaction partners. In an online
      study (n = 284), participants were given the opportunity to report attitudes
      toward and make monetary donations to needy individuals who were described in
      dynamically generated biographies. Using a machine learning and multilevel
      modeling framework, we tested three potential explanations for the facilitatory
      influence of Agreeableness on charitable behavior. We find that Agreeableness
      preferentially increased donations and prosocial attitudes toward targets
      normatively rated as being more deserving. Our results advance understanding of
      person-by-situation interactions in the context of charitable behavior and
      prosocial attitudes. 

PMID- 26312169
TI  - In vitro biomechanical evaluation of internal fixation techniques on the canine
      lumbosacral junction.
AB  - Few biomechanical studies have evaluated the effect of internal stabilization
      techniques after decompressive surgery on the stability of the canine lumbosacral
      junction. The purpose of this canine cadaver study is to evaluate the stability
      of the canine lumbosacral (LS) spine in flexion and extension following
      laminectomy and discectomy and then stabilization with each of the three
      techniques: pins and polymethylmethacrylate (P/PMMA), two dorsal locking plates
      (SOP) or bilateral transarticular facet screws (FACET).Using a cantilever
      biomechanical system, bending moments were applied to the LS and range of motion
      (ROM) was recorded via a rotational potentiometer. With 3 Nm, the ROM (n = 4 in
      each group) for P/PMMA, SOP and FACET were 1.92 +/- 0.96 degrees , 2.56 +/- 0.55
      degrees and 3.18 +/- 1.14 degrees , respectively. With moments up to 35 Nm, the
      P/PMMA specimens appeared stable. Sacroiliac motion in the SOP and FACET groups
      invalidated further comparisons. Each of the stabilization techniques (P/PMMA,
      SOP, and FACET) significantly decreased the range of motion in flexion and
      extension for low bending moments. 

PMID- 26312170
TI  - Environmental influences on the Indo-Pacific octocoral Isis hippuris Linnaeus
      1758 (Alcyonacea: Isididae): genetic fixation or phenotypic plasticity?
AB  - As conspicuous modular components of benthic marine habitats, gorgonian (sea fan)
      octocorals have perplexed taxonomists for centuries through their shear
      diversity, particularly throughout the Indo-Pacific. Phenotypic incongruence
      within and between seemingly unitary lineages across contrasting environments can
      provide the raw material to investigate processes of disruptive selection. Two
      distinct phenotypes of the Isidid Isis hippurisLinnaeus, 1758 partition between
      differing reef environments: long-branched bushy colonies on degraded reefs, and
      short-branched multi/planar colonies on healthy reefs within the Wakatobi Marine
      National Park (WMNP), Indonesia. Multivariate analyses reveal phenotypic traits
      between morphotypes were likely integrated primarily at the colony level with
      increased polyp density and consistently smaller sclerite dimensions at the
      degraded site. Sediment load and turbidity, hence light availability, primarily
      influenced phenotypic differences between the two sites. This distinct
      morphological dissimilarity between the two sites is a reliable indicator of reef
      health; selection primarily acting on colony morphology, porosity through
      branching structure, as well as sclerite diversity and size. ITS2 sequence and
      predicted RNA secondary structure further revealed intraspecific variation
      between I. hippuris morphotypes relative to such environments (PhiST = 0.7683, P
      < 0.001). This evidence suggests-but does not confirm-that I. hippuris
      morphotypes within the WMNP are two separate species; however, to what extent and
      taxonomic assignment requires further investigation across its full geographic
      distribution. Incongruence between colonies present in the WMNP with tenuously
      described Isis alternatives (Isis reticulataNutting, 1910, Isis
      minorbrachyblastaZou, Huang & Wang, 1991), questions the validity of such
      assignments. Furthermore, phylogenetic analyses confirm early taxonomic
      suggestion that the characteristic jointed axis of the Isididae is in fact a
      convergent trait. Thus the polyphyletic nature of the Isididae lies in its type
      species I. hippuris, being unrelated to the rest of its family members. 

PMID- 26312171
TI  - Response of Microtermes mycophagus (Isoptera: Termitidae) to twenty one wood
      species.
AB  - The responses of termite species to bait depend upon the quality of the food used
      in the stations. Woods are the most common food sources for termites but
      different termite species behave differently to different wood species and types.
      The knowledge of the preference status of different wood species to a termite
      species helps in effective monitoring and baiting program. The current study was
      carried out to evaluate the preference of 21 wood species to the termite,
      Microtermes mycophagus in the field by no-choice and choice feeding tests. The
      results indicated silk cotton tree and sacred fig woods as the most preferred
      wood species with mean mass losses of 71.21 +/- 5.09% and 68.38 +/- 7.27% in no
      choice test and 95.02 +/- 1.65% and 91.69 +/- 2.07% in choice tests,
      respectively. White cedar was the least preferred wood species with mean mass
      losses of 7.49 +/- 1.64% and 13.92 +/- 1.89% in no choice and choice feeding
      tests, respectively. Based on present studies, sapwood of silk cotton tree and
      sacred fig may be used in effective monitoring and baiting program against M.
      mycophagus. 

PMID- 26312172
TI  - Understanding text-based persuasion and support tactics of concerned significant
      others.
AB  - The behavior of concerned significant others (CSOs) can have a measurable impact
      on the health and wellness of individuals attempting to meet behavioral and
      health goals, and research is needed to better understand the attributes of text
      based CSO language when encouraging target significant others (TSOs) to achieve
      those goals. In an effort to inform the development of interventions for CSOs,
      this study examined the language content of brief text-based messages generated
      by CSOs to motivate TSOs to achieve a behavioral goal. CSOs generated brief text
      based messages for TSOs for three scenarios: (1) to help TSOs achieve the goal,
      (2) in the event that the TSO is struggling to meet the goal, and (3) in the
      event that the TSO has given up on meeting the goal. Results indicate that there
      was a significant relationship between the tone and compassion of messages
      generated by CSOs, the CSOs' perceptions of TSO motivation, and their expectation
      of a grateful or annoyed reaction by the TSO to their feedback or support.
      Results underscore the importance of attending to patterns in language when CSOs
      communicate with TSOs about goal achievement or failure, and how certain
      variables in the CSOs' perceptions of their TSOs affect these characteristics. 

PMID- 26312173
TI  - Too much of a good thing? An observational study of prolific authors.
AB  - Introduction. Researchers' productivity is usually measured in terms of their
      publication output. A minimum number of publications is required for some medical
      qualifications and professional appointments. However, authoring an unfeasibly
      large number of publications might indicate disregard of authorship criteria or
      even fraud. We therefore examined publication patterns of highly prolific authors
      in 4 medical specialties. Methods. We analysed Medline publications from 2008-12
      using bespoke software to disambiguate individual authors focusing on 4 discrete
      topics (to further reduce the risk of combining publications from authors with
      the same name and affiliation). This enabled us to assess the number and type of
      publications per author per year. Results. While 99% of authors were listed on
      fewer than 20 publications in the 5-year period, 24 authors in the chosen areas
      were listed on at least 25 publications in a single year (i.e., >1 publication
      per 10 working days). Types of publication by the prolific authors varied but
      included substantial numbers of original research papers (not simply editorials
      or letters). Conclusions. Institutions and funders should be alert to unfeasibly
      prolific authors when measuring and creating incentives for researcher
      productivity. 

PMID- 26312174
TI  - Mental disorder recovery correlated with centralities and interactions on an
      online social network.
AB  - Recent research has established both a theoretical basis and strong empirical
      evidence that effective social behavior plays a beneficial role in the
      maintenance of physical and psychological well-being of people. To test whether
      social behavior and well-being are also associated in online communities, we
      studied the correlations between the recovery of patients with mental disorders
      and their behaviors in online social media. As the source of the data related to
      the social behavior and progress of mental recovery, we used PatientsLikeMe
      (PLM), the world's first open-participation research platform for the development
      of patient-centered health outcome measures. We first constructed an online
      social network structure based on patient-to-patient ties among 200 patients
      obtained from PLM. We then characterized patients' online social activities by
      measuring the numbers of "posts and views" and "helpful marks" each patient
      obtained. The patients' recovery data were obtained from their self-reported
      status information that was also available on PLM. We found that some node
      properties (in-degree, eigenvector centrality and PageRank) and the two online
      social activity measures were significantly correlated with patients' recovery.
      Furthermore, we re-collected the patients' recovery data two months after the
      first data collection. We found significant correlations between the patients'
      social behaviors and the second recovery data, which were collected two months
      apart. Our results indicated that social interactions in online communities such
      as PLM were significantly associated with the current and future recoveries of
      patients with mental disorders. 

PMID- 26312175
TI  - Parametric estimation of P(X > Y) for normal distributions in the context of
      probabilistic environmental risk assessment.
AB  - Estimating the risk, P(X > Y), in probabilistic environmental risk assessment of
      nanoparticles is a problem when confronted by potentially small risks and small
      sample sizes of the exposure concentration X and/or the effect concentration Y.
      This is illustrated in the motivating case study of aquatic risk assessment of
      nano-Ag. A non-parametric estimator based on data alone is not sufficient as it
      is limited by sample size. In this paper, we investigate the maximum gain
      possible when making strong parametric assumptions as opposed to making no
      parametric assumptions at all. We compare maximum likelihood and Bayesian
      estimators with the non-parametric estimator and study the influence of sample
      size and risk on the (interval) estimators via simulation. We found that the
      parametric estimators enable us to estimate and bound the risk for smaller sample
      sizes and small risks. Also, the Bayesian estimator outperforms the maximum
      likelihood estimators in terms of coverage and interval lengths and is,
      therefore, preferred in our motivating case study. 

PMID- 26312176
TI  - The effects of leaf litter nutrient pulses on Alliaria petiolata performance.
AB  - Nutrient pulses can facilitate species establishment and spread in new habitats,
      particularly when one species more effectively uses that nutrient pulse.
      Biological differences in nutrient acquisition between native and exotic species
      may facilitate invasions into a variety of habitats including deciduous forest
      understories. Alliaria petiolata (Bieb.) Cavara & Grande is an important invader
      of deciduous forest understories throughout much of North America. These
      understory communities contain many species which perform the majority of their
      growth and reproduction before canopy closure in spring. Because A. petiolata is
      a wintergreen biennial that can be active during autumn and winter, it may
      utilize nutrients released from decaying leaf litter before its competitors. To
      investigate this we manipulated the timing of leaf litter addition (fall or
      spring) and experimentally simulated the nutrient pulse from decaying leaves
      using artificial fertilizer. To determine whether A. petiolata affected the
      abundance of understory competitors, we also removed A. petiolata from one
      treatment. A. petiolata that received early nutrients exhibited greater growth.
      Treatments receiving fall leaf litter or artificial nutrients had greater A.
      petiolata adult biomass than plots receiving spring nutrient additions (leaf
      litter or artificial nutrients). However, fall leaf litter addition had no effect
      on the richness of competitor species. Thus, wintergreen phenology may contribute
      to the spread of A. petiolata through deciduous forest understories, but may not
      explain community-level impacts of A. petiolata in deciduous forests. 

PMID- 26312177
TI  - External morphology of eyes and Nebenaugen of caridean decapods-ecological and
      systematic considerations.
AB  - Most caridean decapods have compound eyes of the reflecting superposition kind,
      and additionally some possess an accessory eye-like organ of unknown function,
      also referred to as the nebenauge. We examined 308 caridean genera to assess the
      general morphology of the eye, rostrum length, eye diameter and the presence or
      absence and, when present, the diameter of the nebenauge. We have attempted to
      relate these data to ecological and taxonomic considerations. We consider there
      to be 6 distinct eye types based on the margin between the eyestalk and cornea.
      The presence of nebenaugen appears to be generally linked to an active lifestyle,
      as evidenced by the fact that species that have nebenaugen tend to have larger
      eyes and are more likely to have a distinct rostrum. We suggest that the
      inconsistencies in its presence/absence under both systematic and ecological
      lenses may indicate that when present it has various roles relating to
      behavioural and physiological rhythms. 

PMID- 26312178
TI  - Response of the rare biosphere to environmental stressors in a highly diverse
      ecosystem (Zodletone spring, OK, USA).
AB  - Within highly diverse ecosystems, the majority of bacterial taxa are present in
      low abundance as members of the rare biosphere. The rationale for the occurrence
      and maintenance of the rare biosphere, and the putative ecological role(s) and
      dynamics of its members within a specific ecosystem is currently debated. We
      hypothesized that in highly diverse ecosystems, a fraction of the rare biosphere
      acts as a backup system that readily responds to environmental disturbances. We
      tested this hypothesis by subjecting sediments from Zodletone spring, a sulfide-
      and sulfur-rich spring in Southwestern OK, to incremental levels of salinity (1,
      2, 3, 4, and 10% NaCl), or temperature (28 degrees , 30 degrees , 32 degrees ,
      and 70  degrees C), and traced the trajectories of rare members of the community
      in response to these manipulations using 16S rRNA gene analysis. Our results
      indicate that multiple rare bacterial taxa are promoted from rare to abundant
      members of the community following such manipulations and that, in general, the
      magnitude of such recruitment is directly proportional to the severity of the
      applied manipulation. Rare members that are phylogenetically distinct from
      abundant taxa in the original sample (unique rare biosphere) played a more
      important role in the microbial community response to environmental disturbances,
      compared to rare members that are phylogenetically similar to abundant taxa in
      the original sample (non-unique rare biosphere). The results emphasize the
      dynamic nature of the rare biosphere, and highlight its complexity and non
      monolithic nature. 

PMID- 26312179
TI  - Face matching in a long task: enforced rest and desk-switching cannot maintain
      identification accuracy.
AB  - In face matching, observers have to decide whether two photographs depict the
      same person or different people. This task is not only remarkably difficult but
      accuracy declines further during prolonged testing. The current study
      investigated whether this decline in long tasks can be eliminated with regular
      rest-breaks (Experiment 1) or room-switching (Experiment 2). Both experiments
      replicated the accuracy decline for long face-matching tasks and showed that this
      could not be eliminated with rest or room-switching. These findings suggest that
      person identification in applied settings, such as passport control, might be
      particularly error-prone due to the long and repetitive nature of the task. The
      experiments also show that it is difficult to counteract these problems. 

PMID- 26312180
TI  - Ichthyoplankton assemblage structure of springs in the Yangtze Estuary revealed
      by biological and environmental visions.
AB  - The ichthyoplankton assemblage structure in the Yangtze Estuary was analyzed
      based on four springs in 1999, 2001, 2004 and 2007 in order to provide detailed
      characterizations of the ichthyoplankton assemblage in springs, examine the long
      term dynamics of spring ichthyoplankton assemblages, and evaluate the influence
      of environmental factors on the spatial distribution and inter-annual variations
      of ichthyoplankton assemblages associated with the Yangtze Estuary. Forty-two
      ichthyoplankton species belonging to 23 families were collected. Engraulidae was
      the most abundant family, including six species and comprising 67.91% of the
      total catch. Only four species (Coilia mystus, Engraulis japonicus, Trachidermis
      fasciatus and Allanetta bleekeri) could be considered dominant, accounting for
      88.70% of total abundance. The structure of the ichthyoplankton spring assemblage
      persisted on an annual basis, with the dominant species reappearing consistently
      even though their abundance fluctuated from year to year. This inter-annual
      variation probably reflects variable environmental conditions influenced by
      jellyfish blooms, declining river flow, and overfishing. Canonical correspondence
      analysis indicated aspatial structure of the ichthyoplankton assemblage in three
      areas: (1) an inner assemblage dominated by C. mystus; (2) a central assemblage
      dominated by A. bleekeri and T. fasciatus; and (3) a shelf assemblage featuring
      E. japonicus. The observed ichthyoplankton assemblage structure appears to be
      strongly influenced by depth, salinity and suspended particulate matter
      gradients. 

PMID- 26312181
TI  - Irrigation and avifaunal change in coastal Northwest Mexico: has irrigated habit
      attracted threatened migratory species?
AB  - Irrigation in desert ecosystems can either reduce or increase species diversity.
      Groundwater pumping often lowers water tables and reduces natural wetlands,
      whereas canal irrigation often creates mesic habitat, resulting in great
      increases in avian diversity from irrigation. Here we compare a dataset of
      potential natural vegetation to recent datasets from areal and satellite imagery
      to show that 60% of the land in the coastal plain of southern Sonora and northern
      Sinaloa lying below 200 m elevation has been converted by irrigation to more
      mesic habitats. We then use the record of bird specimens in the world's museums
      from this same region of Mexico to examine the avian community before and after
      the development of extensive irrigation. In general these museum records show an
      increase in the abundance and diversity of breeding birds associated with mesic
      habitats. Although thorn forest birds have likely decreased in total numbers,
      most are common enough in the remaining thorn forest that collection records did
      not indicate their probable decline. Four migrants having most of their breeding
      ranges in the US or Canada, Yellow-billed Cuckoo, Cliff Swallow, Bell's Vireo,
      and Orchard Oriole, apparently have increased dramatically as breeders in
      irrigated habitats of NW Mexico. Because these species have decreased or even
      largely disappeared as breeding birds in parts of the US or Canada, further
      research should assess whether their increases in new mesic habitats of NW Mexico
      are linked to their declines as breeding birds in Canada and the US For Bell's
      Vireo recent specimens from Sinaloa suggest its new breeding population in NW
      Mexico may be composed partly of the endangered Least Bell's Vireo. 

PMID- 26312182
TI  - A specimen of Rhamphorhynchus with soft tissue preservation, stomach contents and
      a putative coprolite.
AB  - Despite being known for nearly two centuries, new specimens of the derived non
      pterodactyloid pterosaur Rhamphorhynchus continue to be discovered and reveal new
      information about their anatomy and palaeobiology. Here we describe a specimen
      held in the collections of the Royal Tyrrell Museum of Palaeontology, Alberta,
      Canada that shows both preservation and impressions of soft tissues, and also
      preserves material interpreted as stomach contents of vertebrate remains and,
      uniquely, a putative coprolite. The specimen also preserves additional evidence
      for fibers in the uropatagium. 

PMID- 26312183
TI  - Perivascular mast cells regulate vein graft neointimal formation and remodeling.
AB  - Objective. Emerging evidence suggests an important role for mast cells in vein
      graft failure. This study addressed the hypothesis that perivascular mast cells
      regulate in situ vascular inflammatory and proliferative responses and subsequent
      vein graft neointimal lesion formation, using an optimized local mast cell
      reconstitution method. Methods and Results. Neointimal hyperplasia was induced by
      insertion of a vein graft into the right carotid artery in wild type and mast
      cell deficient Kit(W-sh/W-sh) mice. In some experiments, mast cells were
      reconstituted systemically (tail vein injection of bone marrow-derived mast
      cells) or locally (directly into the right neck area) prior to vein grafting.
      Vein graft neointimal lesion formation was significantly (P < 0.05) reduced in
      Kit(W-sh/W-sh) mice. Mast cell deficiency reduced the number of proliferating
      cells, and inhibited L-selectin, CCL2, M-CSF and MIP-3alpha expression in the
      vein grafts. Local but not systemic mast cell reconstitution restored a
      perivascular mast cell population that subsequently promoted neointimal formation
      in mast cell deficient mice. Conclusion. Our data demonstrate that perivascular
      mast cells play a key role in promoting neointima formation by inducing local
      acute inflammatory and proliferative responses. These results suggest that ex
      vivo intraoperative targeting of mast cells may have therapeutic potential for
      the prevention of pathological vein graft remodeling. 

PMID- 26312184
TI  - A glacial survivor of the alpine Mediterranean region: phylogenetic and
      phylogeographic insights into Silene ciliata Pourr. (Caryophyllaceae).
AB  - Silene ciliata Pourr. (Caryophyllaceae) is a species with a highly disjunct
      distribution which inhabits the alpine mountains of the Mediterranean Basin. We
      investigated the phylogeny and phylogeography of the species to (a) clarify the
      long-suggested division of S. ciliata into two subspecies, (b) evaluate its
      phylogenetic origin and (c) assess whether the species' diversification patterns
      were affected by the Mediterranean relief. For this purpose, we collected DNA
      from 25 populations of the species that inhabit the mountains of Portugal, Spain,
      France, Italy, former Yugoslav Republic of Macedonia, Bulgaria and Greece and
      studied the plastid regions rbcL, rps16 and trnL. Major intraspecific variation
      was supported by all analyses, while the possibility of the existence of more
      varieties or subspecies was not favoured. Plastid DNA (cpDNA) evidence was in
      accordance with the division of S. ciliata into the two subspecies, one spreading
      west (Iberian Peninsula and Central Massif) and the other east of the Alps region
      (Italian and Balkan Peninsula). This study proposes that the species'
      geographically disconnected distribution has probably derived from vicariance
      processes and from the Alps acting as a barrier to the species' dispersal. The
      monophyletic origin of the species is highly supported. cpDNA patterns were shown
      independent of the chromosome evolution in the populations and could have
      resulted from a combination of geographic factors providing links and barriers,
      climatic adversities and evolutionary processes that took place during Quaternary
      glaciations. 

PMID- 26312185
TI  - The application of fractional Mel cepstral coefficient in deceptive speech
      detection.
AB  - The inconvenience operation of EEG P300 or functional magnetic resonance imaging
      (FMRI) will be overcome, when the deceptive information can be effectively
      detected from speech signal analysis. In this paper, the fractional Mel cepstral
      coefficient (FrCC) is proposed as the speech character for deception detection.
      The different fractional order can reveal various personalities of the speakers.
      The linear discriminant analysis (LDA) model (which has the ability of global
      optimal vector mapping) is introduced, and the performance of FrCC and MFCC in
      deceptive detection is compared when all the data are mapped to low dimensional.
      Then, the hidden Markov model (HMM) is introduced as a long-term signal analysis
      tool. Twenty-five male and 25 female participants are involved in the experiment.
      The results show that the clustering effect of optimal fractional order FrCC is
      better than that of MFCC. The average accuracy for male and female speaker is
      59.9% and 56.2%, respectively, by using the FrCC under the LDA model. When MFCC
      is used, the accuracy is reduced by 3.2% and 5.9%, respectively, for male and
      female. The accuracy can be increased to 71.0% and 70.2% for male and female
      speakers when HMM is used. Moreover, some individual accuracy is increased over
      20%, or even more than 85%, when FrCC is introduced. The results show that the
      deceptive information is indeed hidden in the speech signals. Therefore, speech
      based psychophysiology calculating may be a valuable research field. 

PMID- 26312186
TI  - Personality and intelligence: persistence, not self-directedness, cooperativeness
      or self-transcendence, is related to twins' cognitive abilities.
AB  - Background. A person-centered approach focusing on the interaction of an
      individual's temperament-character-life events is essential in the path of
      individuals' well-being. In this context, three character traits, Self
      directedness (e.g., self-acceptance, self-control, goal-directed behavior),
      Cooperativeness (e.g., social affiliation, social tolerance, empathy and
      helpfulness) and Self-transcendence (e.g., spiritual acceptance, transpersonal
      identification), measured using Cloninger's model of personality are suggested to
      help the individual to regulate and resolve the conflicts derived from her/his
      temperament combinations as a reaction to life events. However, if character is
      related to the individual's cognitive ability, then this association might limit
      any intervention that focuses on character development. We used data from the
      Child and Adolescent Twin Study in Sweden (CATSS) to investigate the relationship
      between personality and cognitive ability. Method. The sample consisted of 370 15
      year-old twins (159 girls/211 boys), 192 of whom screen-positive with various
      types of mental health problems. We used the Temperament and Character Inventory
      to measure personality and the Wechsler Intelligence Scales for Children (WISC
      IV) to measure intelligence. The relationship was investigated using correlation
      analyses using random-selected twins from each dyad and separately for
      monozygotic and dizygotic twins. Additional analyses investigated the genetic and
      environmental effects on personality and cognitive ability in this specific
      sample. Results. There were no significant correlations between the WISC-IV
      indices and any of the character traits (i.e., Self-directedness,
      Cooperativeness, and Self-transcendence). Persistence was significantly related,
      if weak, to four WISC-IV indices: Verbal Comprehension, Perceptual Reasoning,
      Working Memory, and the Full WISC-IV Scale. Post-hoc cross-twin/cross-trait
      analyses showed that the Persistence-cognitive ability correlation might depend
      on common genetic effects. The WISC-IV indices showed a relatively large genetic
      influence, while earlier findings about the etiology of temperament and character
      traits using the whole CATSS sample were replicated in this sub-sample of twins.
      Conclusions. The results indicate that what individuals make of themselves
      intentionally (i.e., their character) was not associated to intelligence.
      Persistence, a temperament dimension that measures heritable individual
      differences in eagerness of effort, ambition, perfectionism, and resistance to
      discouragement despite frustration and fatigue, was weakly linked to
      intelligence. Suggesting that, at least during adolescence, interventions
      targeting character development are not limited by the individual's intelligence.

PMID- 26312187
TI  - Neutering of cats and dogs in Ireland; pet owner self-reported perceptions of
      enabling and disabling factors in the decision to neuter.
AB  - Background. Failure among pet owners to neuter their pets results in increased
      straying and overpopulation problems. Variations in neutering levels can be
      explained by cultural differences, differences in economic status in rural and
      urban locations, and owner perceptions about their pet. There are also
      differences between male and female pet owners. There is no research pertaining
      to Irish pet owner attitudes towards neutering their pets. This paper identified
      the perceptions of a sample of Irish cat and dog owners that influenced their
      decisions on pet neutering. Methods. This study was conducted using social
      science (qualitative) methods, including an interview-administered survey
      questionnaire and focus group discussions. Data was coded and managed using Nvivo
      8 qualitative data analysis software. Results. Focus groups were conducted with
      43 pet (cats and dogs) owners. Two major categories relating to the decision to
      neuter were identified: (1) enabling perceptions in the decision to neuter
      (subcategories were: controlling unwanted pet behaviour; positive perceptions
      regarding pet health and welfare outcomes; perceived owner responsibility; pet
      function; and the influence of veterinary advice), and (2) disabling perceptions
      in the decision to neuter (subcategories were: perceived financial cost of
      neutering; perceived adequacy of existing controls; and negative perceptions
      regarding pet health and welfare outcomes). Discussion. Pet owner sense of
      responsibility and control are two central issues to the decision to neuter their
      pets. Understanding how pet owners feel about topics such as pet neutering, can
      help improve initiatives aimed at emphasising the responsibility of population
      control of cats and dogs. 

PMID- 26312188
TI  - Biological and ecological traits of marine species.
AB  - This paper reviews the utility and availability of biological and ecological
      traits for marine species so as to prioritise the development of a world database
      on marine species traits. In addition, the 'status' of species for conservation,
      that is, whether they are introduced or invasive, of fishery or aquaculture
      interest, harmful, or used as an ecological indicator, were reviewed because
      these attributes are of particular interest to society. Whereas traits are an
      enduring characteristic of a species and/or population, a species status may vary
      geographically and over time. Criteria for selecting traits were that they could
      be applied to most taxa, were easily available, and their inclusion would result
      in new research and/or management applications. Numerical traits were favoured
      over categorical. Habitat was excluded as it can be derived from a selection of
      these traits. Ten traits were prioritized for inclusion in the most comprehensive
      open access database on marine species (World Register of Marine Species), namely
      taxonomic classification, environment, geography, depth, substratum, mobility,
      skeleton, diet, body size and reproduction. These traits and statuses are being
      added to the database and new use cases may further subdivide and expand upon
      them. 

PMID- 26312189
TI  - Coalescent: an open-science framework for importance sampling in coalescent
      theory.
AB  - Background. In coalescent theory, computer programs often use importance sampling
      to calculate likelihoods and other statistical quantities. An importance sampling
      scheme can exploit human intuition to improve statistical efficiency of
      computations, but unfortunately, in the absence of general computer frameworks on
      importance sampling, researchers often struggle to translate new sampling schemes
      computationally or benchmark against different schemes, in a manner that is
      reliable and maintainable. Moreover, most studies use computer programs lacking a
      convenient user interface or the flexibility to meet the current demands of open
      science. In particular, current computer frameworks can only evaluate the
      efficiency of a single importance sampling scheme or compare the efficiencies of
      different schemes in an ad hoc manner. Results. We have designed a general
      framework (http://coalescent.sourceforge.net; language: Java; License: GPLv3) for
      importance sampling that computes likelihoods under the standard neutral
      coalescent model of a single, well-mixed population of constant size over time
      following infinite sites model of mutation. The framework models the necessary
      core concepts, comes integrated with several data sets of varying size,
      implements the standard competing proposals, and integrates tightly with our
      previous framework for calculating exact probabilities. For a given dataset, it
      computes the likelihood and provides the maximum likelihood estimate of the
      mutation parameter. Well-known benchmarks in the coalescent literature validate
      the accuracy of the framework. The framework provides an intuitive user interface
      with minimal clutter. For performance, the framework switches automatically to
      modern multicore hardware, if available. It runs on three major platforms
      (Windows, Mac and Linux). Extensive tests and coverage make the framework
      reliable and maintainable. Conclusions. In coalescent theory, many studies of
      computational efficiency consider only effective sample size. Here, we evaluate
      proposals in the coalescent literature, to discover that the order of efficiency
      among the three importance sampling schemes changes when one considers running
      time as well as effective sample size. We also describe a computational technique
      called "just-in-time delegation" available to improve the trade-off between
      running time and precision by constructing improved importance sampling schemes
      from existing ones. Thus, our systems approach is a potential solution to the
      "2(8) programs problem" highlighted by Felsenstein, because it provides the
      flexibility to include or exclude various features of similar coalescent models
      or importance sampling schemes. 

PMID- 26312190
TI  - Low relative error in consumer-grade GPS units make them ideal for measuring
      small-scale animal movement patterns.
AB  - Consumer-grade GPS units are a staple of modern field ecology, but the relatively
      large error radii reported by manufacturers (up to 10 m) ostensibly precludes
      their utility in measuring fine-scale movement of small animals such as insects.
      Here we demonstrate that for data collected at fine spatio-temporal scales, these
      devices can produce exceptionally accurate data on step-length and movement
      patterns of small animals. With an understanding of the properties of GPS error
      and how it arises, it is possible, using a simple field protocol, to use consumer
      grade GPS units to collect step-length data for the movement of small animals
      that introduces a median error as small as 11 cm. These small error rates were
      measured in controlled observations of real butterfly movement. Similar
      conclusions were reached using a ground-truth test track prepared with a field
      tape and compass and subsequently measured 20 times using the same methodology as
      the butterfly tracking. Median error in the ground-truth track was slightly
      higher than the field data, mostly between 20 and 30 cm, but even for the
      smallest ground-truth step (70 cm), this is still a signal-to-noise ratio of 3:1,
      and for steps of 3 m or more, the ratio is greater than 10:1. Such small errors
      relative to the movements being measured make these inexpensive units useful for
      measuring insect and other small animal movements on small to intermediate scales
      with budgets orders of magnitude lower than survey-grade units used in past
      studies. As an additional advantage, these units are simpler to operate, and
      insect or other small animal trackways can be collected more quickly than either
      survey-grade units or more traditional ruler/gird approaches. 

PMID- 26312191
TI  - Winter Aconite (Eranthis hyemalis) Lectin as a cytotoxic effector in the
      lifecycle of Caenorhabditis elegans.
AB  - The lectin found in the tubers of the Winter Aconite (Eranthis hyemalis) plant is
      an N-acetyl-D-galactosamine specific Type II Ribosome Inactivating Protein (RIP);
      Type II RIPs have shown anti-cancer properties, and hence have potential as
      therapeutic agents. Here we present a modified protocol for the extraction and
      purification of the E. hyemalis lectin (EHL) using affinity chromatography. De
      novo amino acid sequencing of EHL confirms its classification as a Type II
      Ribosome Inactivating Protein. The biocidal properties of EHL have been
      investigated against the nematode Caenorhabditis elegans. Arrested first stage
      larvae treated with EHL have shown some direct mortality, with surviving larvae
      subsequently showing a range of phenotypes including food avoidance, reduced
      fecundity, developmental delay and constitutive dauer larvae formation. Both
      inappropriate dauer larvae development and failure to locate to bacterial food
      source are consistent with the disruption of chemosensory function and the
      ablation of amphid neurons. Further investigation indicates that mutations that
      disrupt normal amphid formation can block the EHL-induced dauer larvae formation.
      In combination, these phenotypes indicate that EHL is cytotoxic and suggest a
      cell specific activity against the amphid neurons of C. elegans. 

PMID- 26312192
TI  - An empirical review: Characteristics of plant microsatellite markers that confer
      higher levels of genetic variation.
AB  - During microsatellite marker development, researchers must choose from a pool of
      possible primer pairs to further test in their species of interest. In many
      cases, the goal is maximizing detectable levels of genetic variation. To guide
      researchers and determine which markers are associated with higher levels of
      genetic variation, we conducted a literature review based on 6782 genomic
      microsatellite markers published from 1997-2012. We examined relationships
      between heterozygosity (H e or H o) or allele number (A) with the following
      marker characteristics: repeat type, motif length, motif region, repeat
      frequency, and microsatellite size. Variation across taxonomic groups was also
      analyzed. There were significant differences between imperfect and perfect repeat
      types in A and H e. Dinucleotide motifs exhibited significantly higher A, H e,
      and H o than most other motifs. Repeat frequency and motif region were positively
      correlated with A, H e, and H o, but correlations with microsatellite size were
      minimal. Higher taxonomic groups were disproportionately represented in the
      literature and showed little consistency. In conclusion, researchers should
      carefully consider marker characteristics so they can be tailored to the desired
      application. If researchers aim to target high genetic variation, dinucleotide
      motif lengths with large repeat frequencies may be best. 

PMID- 26312193
TI  - Plann: A command-line application for annotating plastome sequences.
AB  - PREMISE OF THE STUDY: Plann automates the process of annotating a plastome
      sequence in GenBank format for either downstream processing or for GenBank
      submission by annotating a new plastome based on a similar, well-annotated
      plastome. METHODS AND RESULTS: Plann is a Perl script to be executed on the
      command line. Plann compares a new plastome sequence to the features annotated in
      a reference plastome and then shifts the intervals of any matching features to
      the locations in the new plastome. Plann's output can be used in the National
      Center for Biotechnology Information's tbl2asn to create a Sequin file for
      GenBank submission. CONCLUSIONS: Unlike Web-based annotation packages, Plann is a
      locally executable script that will accurately annotate a plastome sequence to a
      locally specified reference plastome. Because it executes from the command line,
      it is ready to use in other software pipelines and can be easily rerun as a draft
      plastome is improved.

PMID- 26312194
TI  - Microsatellite markers for studies with the carnivorous plant Philcoxia minensis
      (Plantaginaceae).
AB  - PREMISE OF THE STUDY: Microsatellite markers were developed for the critically
      endangered carnivorous species Philcoxia minensis (Plantaginaceae) for further
      population genetic studies aiming at its conservation. METHODS AND RESULTS: We
      identified 29 clones containing 40 microsatellites from a genomic enriched
      library. A total of 27 primer pairs were developed and evaluated in 30
      individuals of a natural P. minensis population. Seventeen markers successfully
      presented amplification products within the expected size range, of which 12 were
      polymorphic. The expected and observed heterozygosities ranged from 0.03 to 0.65
      and from 0.00 to 0.77, respectively. Positive transferability with the related
      species P. bahiensis was observed for the same 17 markers. CONCLUSIONS: The 12
      polymorphic microsatellite markers are suitable for studies in genetic diversity
      and structure, mating system, and gene flow in P. minensis and also may be useful
      for similar issues regarding the related species P. bahiensis.

PMID- 26312195
TI  - Development and characterization of polymorphic microsatellite loci for Saxifraga
      egregia (Saxifragaceae).
AB  - PREMISE OF THE STUDY: Saxifraga egregia (Saxifragaceae) is a perennial herb that
      is endemic to the Qinghai-Tibet Plateau. We developed 12 polymorphic
      microsatellite loci for S. egregia to investigate its population genetics.
      METHODS AND RESULTS: Forty-eight pairs of microsatellite primers (including 36
      monomorphic loci) were isolated and characterized by magnetic bead enrichment.
      Twelve of these markers showed polymorphism, and the number of alleles per locus
      ranged from four to 14 across 50 individuals from three populations of S.
      egregia. No linkage disequilibrium was detected in any pair of loci. CONCLUSIONS:
      These polymorphic markers are expected to be helpful in further studies on the
      systematics and phylogeography of S. egregia in the Qinghai-Tibet Plateau.

PMID- 26312197
TI  - Development of microsatellite markers in Ilex kaushue (Aquifoliaceae), a
      medicinal plant species.
AB  - PREMISE OF THE STUDY: Microsatellite markers were developed for Ilex kaushue
      (Aquifoliaceae), a medicinal plant with extremely small wild populations that
      exists in fragmented habitats, to assess and protect its genetic diversity.
      METHODS AND RESULTS: Using 454 GS FLX Titanium sequencing, 16 microsatellite
      primer sets were isolated and characterized. Fifteen of these markers were
      polymorphic. The number of alleles per locus ranged from one to nine across 22
      individuals from both cultivated and wild populations. The observed and expected
      heterozygosity in these two populations ranged from 0.000 to 1.000 and from 0.000
      to 0.785, respectively. CONCLUSIONS: These markers will be useful in studies on
      genetic diversity of I. kaushue.

PMID- 26312196
TI  - A protocol for targeted enrichment of intron-containing sequence markers for
      recent radiations: A phylogenomic example from Heuchera (Saxifragaceae).
AB  - PREMISE OF THE STUDY: Phylogenetic inference is moving to large multilocus data
      sets, yet there remains uncertainty in the choice of marker and sequencing method
      at low taxonomic levels. To address this gap, we present a method for enriching
      long loci spanning intron-exon boundaries in the genus Heuchera. METHODS: Two
      hundred seventy-eight loci were designed using a splice-site prediction method
      combining transcriptomic and genomic data. Biotinylated probes were designed for
      enrichment of these loci. Reference-based assembly was performed using genomic
      references; additionally, chloroplast and mitochondrial genomes were used as
      references for off-target reads. The data were aligned and subjected to
      coalescent and concatenated phylogenetic analyses to demonstrate support for
      major relationships. RESULTS: Complete or nearly complete (>99%) sequences were
      assembled from essentially all loci from all taxa. Aligned introns showed a
      fourfold increase in divergence as opposed to exons. Concatenated analysis gave
      decisive support to all nodes, and support was also high and relationships mostly
      similar in the coalescent analysis. Organellar phylogenies were also well
      supported and conflicted with the nuclear signal. DISCUSSION: Our approach shows
      promise for resolving a recent radiation. Enrichment for introns is highly
      successful with little or no sequencing dropout at low taxonomic levels despite
      higher substitution and indel frequencies, and should be exploited in studies of
      species complexes.

PMID- 26312198
TI  - Development of nuclear and chloroplast microsatellite markers for the endangered
      conifer Callitris sulcata (Cupressaceae).
AB  - PREMISE OF THE STUDY: Microsatellite markers were developed for Callitris sulcata
      (Cupressaceae), an endangered conifer species in New Caledonia. METHODS AND
      RESULTS: Using sequencing by synthesis (SBS) of an RNA-Seq library, 15
      polymorphic nuclear and chloroplast microsatellite markers were developed. When
      evaluated with 48 individuals, these markers showed genetic variations ranging
      from two to 15 alleles and expected heterozygosity ranging from 0 to 0.881.
      CONCLUSIONS: These markers will be useful for examining the genetic diversity and
      structure of remaining wild populations and improving the genetic status of ex
      situ populations.

PMID- 26312199
TI  - Microsatellite markers for the Pilosella alpicola group (Hieraciinae, Asteraceae)
      and their cross-amplification in other Hieraciinae genera.
AB  - PREMISE OF THE STUDY: Microsatellite markers were developed for the Pilosella
      alpicola group (Asteraceae), comprising four closely related species distributed
      in subalpine areas of Europe. These species are believed to have diverged
      recently, but display contrasting cytogeographic patterns and variation in
      breeding systems, representing a promising model system for studying plant
      speciation, adaptation, and recent polyploidization. METHODS AND RESULTS: We
      developed 17 microsatellite markers for the P. alpicola group using 454
      sequencing. Sixteen markers were polymorphic, with the number of alleles per
      locus ranging from seven to 16 and observed and expected heterozygosity ranging
      from 0.45 to 0.84 and 0.72 to 0.92, respectively. Ten and five loci amplified in
      the related species, P. echioides and P. officinarum, respectively, but only two
      in Andryala and one in Hieracium s. str. CONCLUSIONS: The developed
      microsatellite markers have high potential to become useful tools to study
      microevolutionary processes in the P. alpicola group and related Pilosella
      species.

PMID- 26312200
TI  - Characterization of 13 microsatellite markers for Calochortus gunnisonii
      (Liliaceae) from Illumina MiSeq sequencing.
AB  - PREMISE OF THE STUDY: Microsatellite primers were designed for Calochortus
      gunnisonii (Liliaceae), a montane lily species of the central and southern Rocky
      Mountains, using next-generation DNA sequencing. The markers will be used to
      investigate population structure, genetic diversity, and demographic history.
      METHODS AND RESULTS: Thirteen polymorphic microsatellite loci were isolated from
      C. gunnisonii using Illumina MiSeq next-generation DNA sequencing and
      bioinformatic screening. The mean number of alleles per locus ranged from 4.15 to
      5.92 (avg. = 4.97). Observed and expected heterozygosity ranged from 0.077 to
      0.871 and 0.213 to 0.782, respectively. The primers were also tested for cross
      species amplification value with C. flexuosus, C. nuttallii, C. kennedyi var.
      kennedyi, and C. subalpinus. CONCLUSIONS: These primers will be useful for
      genetic and evolutionary studies across C. gunnisonii's range within the southern
      and central Rocky Mountains. Furthermore, these markers have proven valuable for
      cross-species amplifications within Calochortus.

PMID- 26312201
TI  - Quasi two day wave-related variability in the background dynamics and composition
      of the mesosphere/thermosphere and the ionosphere.
AB  - : Dissipating planetary waves in the mesosphere/lower thermosphere (MLT) region
      may cause changes in the background dynamics of that region, subsequently driving
      variability throughout the broader thermosphere/ionosphere system via mixing due
      to the induced circulation changes. We report the results of case studies
      examining the possibility of such coupling during the northern winter in the
      context of the quasi two day wave (QTDW)-a planetary wave that recurrently grows
      to large amplitudes from the summer MLT during the postsolstice period. Six
      distinct QTDW events between 2003 and 2011 are identified in the MLT using
      Sounding of the Atmosphere using Broadband Emission Radiometry temperature
      observations. Concurrent changes to the background zonal winds, zonal mean column
      O/N2 density ratio, and ionospheric total electron content (TEC) are examined
      using data sets from Thermosphere Ionosphere Mesosphere Energetics and Dynamics
      Doppler Interferometer, Global Ultraviolet Imager, and Global Ionospheric Maps,
      respectively. We find that in the 5-10 days following a QTDW event, the
      background zonal winds in the MLT show patterns of eastward and westward
      anomalies in the low and middle latitudes consistent with past modeling studies
      on QTDW-induced mean wind forcing, both below and at turbopause altitudes. This
      is accompanied by potentially related decreases in zonal mean thermospheric
      column O/N2, as well as to low-latitude TECs. The recurrent nature of the above
      changes during the six QTDW events examined point to an avenue for vertical
      coupling via background dynamics and chemistry of the thermosphere/ionosphere not
      previously observed. KEY POINTS: Dissipating planetary waves (PWs) in the MLT can
      drive background wind changesMixing from dissipating PWs drive
      thermosphere/ionosphere composition changesFirst observations of QTDW-driven
      variability from this mechanism.

PMID- 26312202
TI  - Novel way to investigate evolution of children refractory epilepsy by complexity
      metrics in massive information.
AB  - Epilepsy demands a major burden at global levels. Worldwide, about 1% of people
      suffer epilepsy and 30% of them (0.3%) are anticonvulsants resistant. Among them,
      some children epilepsies are peculiarly difficult to deal with as Doose syndrome
      (DS). Doose syndrome is a very complicated type of children cryptogenic
      refractory epilepsy (CCRE) which is traditionally studied by analysis of complex
      electrencephalograms (EEG) by neurologists. CCRE are affections which evolve in a
      course of many years and customarily, questions such as on which year was the kid
      healthiest (less seizures) and on which region of the brain (channel) the
      affection has been progressing more negatively are very difficult or even
      impossible to answer as a result of the quantity of EEG recorded through the
      patient's life. These questions can now be answered by the application of
      entropies to massive information contained in many EEG. CCRE can not always be
      cured and have not been investigated from a mathematical viewpoint as far as we
      are concerned. In this work, a set of 80 time series (distributed equally in four
      yearly recorded EEG) is studied in order to support pediatrician neurologists to
      understand better the evolution of this syndrome in the long term. Our
      contribution is to support multichannel long term analysis of CCRE by observing
      simple entropy plots instead of studying long rolls of traditional EEG graphs. A
      comparative analysis among aproximate entropy, sample entropy, our versions of
      multiscale entropy (MSE) and composite multiscale entropy revealed that our
      refined MSE was the most convenient complexity measure to describe DS.
      Additionally, a new entropy parameter is proposed and is referred to as bivariate
      MSE (BMSE). Such BMSE will provide graphical information in much longer term than
      MSE. 

PMID- 26312204
TI  - Analysis of ALK gene in 133 patients with breast cancer revealed polysomy of
      chromosome 2 and no ALK amplification.
AB  - ALK has emerged as a novel tumorigenic factor in several epithelial human
      cancers. Crizotinib, an ALK tyrosine kinase inhibitor, is currently approved to
      treat lung cancer patients exhibiting ALK gene rearrangements. Our goal was to
      determine the incidence of ALK aberrations in relation to different breast cancer
      types. Tissue micro-arrays were constructed of ER+/PR+/-/HER2- (n = 37), ER-/PR
      /HER2+ (n = 15), ER-/PR-/HER2- (n = 61) and ER+/PR+/HER2+ (n = 20) breast
      cancers; including 13 inflammatory breast carcinomas. FISH was performed using
      ALK break-apart and chromosome 2 centromere enumeration probes (CEP2). Neither
      ALK rearrangements nor amplification were identified in the 133 breast cancer
      cases evaluated. However, copy number gains (CNG) of ALK were identified in 82 of
      133 patients (62 %). The CEP2 analysis revealed polysomy of chromosome 2 in all
      HCNG and LCNG cases, indicating the CNG of ALK are due to polysomy of chromosome
      2, rather than true amplification of ALK. To conclude, we observed CNG of ALK
      secondary to chromosome 2 polysomy in a significant percentage of breast cancer
      cases, a phenomenon similar to polysomy 17. This study is one of the largest
      studies to have investigated ALK aberrations in breast cancer and the only study
      to include all subtypes. 

PMID- 26312203
TI  - Protective effect of Emblica-officinalis in arsenic induced biochemical
      alteration and inflammation in mice.
AB  - Exposure to arsenic in individuals has been found to be associated with immune
      related problems. In earlier studies, we have demonstrated that amla protects
      against arsenic induced oxidative stress and apoptosis in thymus and spleen of
      mice. In continuation to that the present study has therefore been focused to
      investigate the protective efficacy of amla in arsenic induced inflammation and
      immunotoxicity in mice. The results showed that arsenic treatment significantly
      increased serum urea levels (69 %), glucose levels (48 %) and triglyceride levels
      (66 %) as compared to controls. Mice exposed to arsenic exhibited significant
      increased in TNF-alpha (4.3-fold), serum Interleukin-1 beta (threefold),
      Interleukin-6 (3.8-fold) as compared to controls. Arsenic exposure increased the
      relative frequency of CD8+ (Tc) cells sub-population (18.9 %) and decreased CD4+
      (Th) cells (2.6 %). Arsenic exposure also significantly decreased T (CD3) and B
      (CD19) cells (21.1 %) as compared to controls. Simultaneously treatment with
      arsenic and amla significantly inhibited serum urea levels (47 %), glucose levels
      (50 %) and triglyceride levels (14 %). It also significantly decreased the TNF
      alpha (1.1-fold), levels of IL-1beta (1.6-fold), levels of Interleukin-6 (1.3
      fold) in serum as compared to those treated with arsenic alone. Simultaneously
      treatment with arsenic and amla restored the alterations in CD8+ and CD4+ cells
      and also recovered the damages in B and T sub cells population. Results of the
      present study clearly indicate that arsenic induced immunotoxicity linked with
      inflammation has been significantly protected through simultaneous treatment with
      arsenic and amla that was due to anti-inflammatory and antioxidant activity of
      amla. 

PMID- 26312205
TI  - Effect of dietary formic acid and astaxanthin on the survival and growth of
      Pacific white shrimp (Litopenaeus vannamei) and their resistance to Vibrio
      parahaemolyticus.
AB  - A 90-day feeding trial was conducted to evaluate the effects of formic acid (FA)
      and astaxanthin (AX) on growth, survival, immune parameters, and tolerance to
      Vibrio infection in Pacific white shrimp. The study was divided into two
      experiments. In experiment 1, postlarvae-12 were randomly distributed into six
      groups and then fed four times daily with six experimental diets contained 0.3 %
      FA, 0.6 % FA, 50 ppm AX, 0.3 % FA + 50 ppm AX, 0.6 % FA + 50 ppm AX, or none of
      these supplements (control diet). After 60 days of the feeding trials, the body
      weight of all treatment groups was not significantly different from the control
      group, although shrimp fed formic acid had significantly lower body weight than
      shrimp fed 50 ppm AX. However, the 0.6 % FA + 50 ppm AX group had a significantly
      higher survival rate (82.33 +/- 8.32 %) than the control group (64.33 +/- 10.12
      %). In experiment 2, Vibrio parahaemolyticus was added to each tank to obtain a
      final concentration of 10(4) colony-forming units/mL. Each treatment group
      received the aforementioned diets for another 30 days. At the end of this
      experiment, there was no difference in the weight gain among all experimental
      groups. However, the survival rate of shrimps whose diet included FA, AX, and
      their combination (in the range of 45.83-67.50 %) was significantly higher than
      the control group (20.00 +/- 17.32 %). FA-fed shrimps also had significantly
      lower total intestinal bacteria and Vibrio spp. counts, while immune parameters
      [total hemocyte count (THC), phagocytosis activity, phenoloxidase (PO) activity,
      and superoxide dismutase (SOD) activity] of AX-fed groups were significantly
      improved compared with the other groups. In conclusion, FA, AX, and their
      combination are useful in shrimp aquaculture. 

PMID- 26312206
TI  - Process modeling and bottleneck mining in online peer-review systems.
AB  - This paper is divided into three main parts. In the first part of the study, we
      captured, collected and formatted an event log describing the handling of reviews
      for proceedings of an international conference in Thailand. In the second part,
      we used several process mining techniques in order to discover process models,
      social, organizational, and hierarchical structures from the proceeding's event
      log. In the third part, we detected the deviations and bottlenecks of the peer
      review process by comparing the observed events (i.e., authentic dataset) with a
      pre-defined model (i.e., master map). Finally, we investigated the performance
      information as well as the total waiting time in order to improve the
      effectiveness and efficiency of the online submission and peer review system for
      the prospective conferences and seminars. Consequently, the main goals of the
      study were as follows: (1) to convert the collected event log into the
      appropriate format supported by process mining analysis tools, (2) to discover
      process models and to construct social networks based on the collected event log,
      and (3) to find deviations, discrepancies and bottlenecks between the collected
      event log and the master pre-defined model. The results showed that although each
      paper was initially sent to three different reviewers; it was not always possible
      to make a decision after the first round of reviewing; therefore, additional
      reviewers were invited. In total, all the accepted and rejected manuscripts were
      reviewed by an average of 3.9 and 3.2 expert reviewers, respectively. Moreover,
      obvious violations of the rules and regulations relating to careless or
      inappropriate peer review of a manuscript-committed by the editorial board and
      other staff-were identified. Nine blocks of activity in the authentic dataset
      were not completely compatible with the activities defined in the master model.
      Also, five of the activity traces were not correctly enabled, and seven
      activities were missed within the online submission system. On the other hand,
      dealing with the feedback (comments) received from the first and the third
      reviewers; the conference committee members and the organizers did not attend to
      those feedback/comments in a timely manner. 

PMID- 26312207
TI  - Enhanced oral bioavailability of vancomycin in rats treated with long-term
      parenteral nutrition.
AB  - Long-term parenteral nutrition (PN) can induce intestinal atrophy, leading to a
      loss of epithelial integrity in the small intestines. This change may alter the
      intestinal permeability of vancomycin (VCM), a non-absorbable antibiotic. The aim
      of the present study was to investigate the effect of PN on the pharmacokinetics
      of VCM in rats. VCM was intravenously (5 mg/kg) or intraduodenally (20 mg/kg)
      administered to control and PN rats, which were prepared by administration of PN
      for 9 days. After intravenous administration, there were no significant
      differences in any of the VCM pharmacokinetic parameters between the control and
      PN rats. However, after intraduodenal administration, the maximum concentration
      and area under the plasma concentration-time curve of VCM in PN rats was
      approximately 2.4- and 2.6-fold higher, respectively, than in the control rats;
      the calculated bioavailability was approximately 0.5 and 1.3 % in control and PN
      rats, respectively. These results indicated that PN administration did not affect
      VCM disposition, but enhanced VCM absorption; however, the enhanced oral VCM
      bioavailability was statistically, not clinically, significant. Therefore, while
      long-term PN administration may play a role in the enhancement of VCM
      bioavailability, this effect may be negligible without any complications. 

PMID- 26312208
TI  - Agrobacterium rhizogenes mediated hairy root induction in endangered Berberis
      aristata DC.
AB  - An efficient protocol for hairy root induction in Berberis aristata DC. was
      established using two different strains of Agrobacterium rhizogenes, MTCC 532 and
      2364 from IMTECH (Institute of Microbial Technology), Chandigarh, India. The
      strain 532 was more effective than strain 2364 in hairy root induction and in
      vitro grown callus (61.11 +/- 1.60 % transformation frequency) was found to be
      suitable explant in comparison to leaves (42.59 +/- 0.92 % transformation
      frequency) and nodal segments (34.25 +/- 0.92 % transformation frequency) of in
      vitro grown microshoots for hairy root induction. The presence of rol A and rol B
      genes during amplification confirmed the transgenic nature of hairy roots and
      transformed callus. Transformation frequency of callus was further enhanced (from
      61.11 +/- 1.60 % to 72.22 +/- 1.60 %; when infection time was 1 h) by using
      acetosyringone (100 uM) during co-cultivation period (48 h) on semisolid MS
      (Murashige and Skoog) medium. In conclusion, this study describes the protocol
      for hairy root induction which could further be useful for the production of
      berberin and may reduce the overharvesting of this endangered species from its
      natural habitat. 

PMID- 26312209
TI  - Luteolin inhibits progestin-dependent angiogenesis, stem cell-like
      characteristics, and growth of human breast cancer xenografts.
AB  - PURPOSE: Clinical trials and epidemiological evidence have shown that combined
      estrogen/progestin hormone replacement therapy, but not estrogen therapy alone,
      increases breast cancer risk in post-menopausal women. Previously we have shown
      that natural and synthetic progestins, including the widely used synthetic
      progestin medroxyprogesterone acetate (MPA), increase production of a potent
      angiogenic factor, vascular endothelial growth factor (VEGF), in human breast
      cancer cells, potentially providing an explanation for progestin's mechanism of
      action. Here, we tested the effects of luteolin (LU), a flavonoid commonly found
      in fruits and vegetables, on inhibiting progestin-dependent VEGF induction and
      angiogenesis in human breast cancer cells, inhibiting stem cell-like
      characteristics, as well as breast cancer cell xenograft tumor growth in vivo and
      expression of angiogenesis markers. METHODS: Viability of both T47-D and BT-474
      cells was measured using sulforhodamine B assays. Enzyme-linked immunosorbent
      assays were used to monitor VEGF secretion from breast cancer cells. Progestin
      dependent xenograft tumor growth was used to determine LU effects in vivo. CD31
      immunohistochemistry was used to determine blood-vessel density in xenograft
      tumors. CD44 expression, aldehyde dehydrogenase activity, and mammosphere
      formation assays were used to monitor stem cell-like characteristics of breast
      cancer cells. RESULTS: Luteolin treatment reduced breast cancer cell viability,
      progestin-dependent VEGF secretion from breast cancer cells, and growth of MPA
      dependent human breast cancer cell xenograft tumors in nude mice. LU treatment
      also decreased xenograft tumor VEGF expression and blood-vessel density.
      Furthermore, LU blocked MPA-induced acquisition of stem cell-like properties by
      breast cancer cells. CONCLUSIONS: Luteolin effectively blocks progestin-dependent
      human breast cancer tumor growth and the stem cell-like phenotype in human breast
      cancer cells.

PMID- 26312210
TI  - Acute renal allograft dysfunction due to cecal volvulus: a case report.
AB  - PURPOSE: Among kidney transplant recipients with acute kidney injury, the
      differential diagnosis must be broadened to include conditions such as rejection,
      immunocompromised host infections, anatomic pathologies, and recurrent or de novo
      glomerular diseases. In this case report, we describe an unusual cause of acute
      renal allograft injury due to external compression of the allograft ureter.
      METHODS: Retrospective review; case report. RESULTS: The patient developed acute
      kidney injury of the renal allograft due to external compression of the allograft
      ureter coincident with a cecal volvulus. The patient underwent lysis of
      adhesions, right hemicolectomy, and end ileostomy creation with resolution of
      acute kidney injury. CONCLUSIONS: Cecal volvulus is an uncommon cause of bowel
      obstruction and is often associated with adhesions following abdominal surgery.
      To our knowledge, cecal volvulus has not previously been reported as a direct
      contributor to acute kidney injury. This case highlights the need for a
      systematic approach to the patient with acute kidney injury and the special
      considerations involved in the diagnosis of renal failure in the kidney
      transplant population.

PMID- 26312211
TI  - Precipitation Extremes Under Climate Change.
AB  - The response of precipitation extremes to climate change is considered using
      results from theory, modeling, and observations, with a focus on the physical
      factors that control the response. Observations and simulations with climate
      models show that precipitation extremes intensify in response to a warming
      climate. However, the sensitivity of precipitation extremes to warming remains
      uncertain when convection is important, and it may be higher in the tropics than
      the extratropics. Several physical contributions govern the response of
      precipitation extremes. The thermodynamic contribution is robust and well
      understood, but theoretical understanding of the microphysical and dynamical
      contributions is still being developed. Orographic precipitation extremes and
      snowfall extremes respond differently from other precipitation extremes and
      require particular attention. Outstanding research challenges include the
      influence of mesoscale convective organization, the dependence on the duration
      considered, and the need to better constrain the sensitivity of tropical
      precipitation extremes to warming.

PMID- 26312212
TI  - Robot assisted adrenalectomy: a handy tool or glorified obsession?
AB  - Robotic surgery has recently expanded its horizon in urology apart from radical
      prostatectomy, one of them being adrenalectomy. Till now, laparoscopic
      adrenalectomy has established itself as the procedure of choice for benign
      adrenal disorders. Brandao et al. have recently accomplished a thorough
      systematic review and meta-analysis of nine trials comparing laparoscopic and
      robotic adrenalectomy. There was no significant difference between the two groups
      in terms of conversion rate [odds ratio (OR): 0.82; 95% CI, 0.39-1.75; P=0.61]
      and operative time (WMD: 5.88; 95% CI, -6.02 to 17.79; P=0.33). There was a
      significantly longer hospital stay in the conventional laparoscopic group (WMD: 
      0.43; 95% CI, -0.56 to -0.30; P<0.00001), as well as a higher estimated blood
      loss (WMD: -18.21; 95% CI, -29.11 to -7.32; P=0.001). There was also no
      statistically significant difference in terms of postoperative complication rate.
      The authors seem to support the use of robot for adrenalectomy. However, robotic
      surgery suffers from cost issues and some technical drawbacks that limit its use
      in routine practice. Larger and appropriately powered randomized controlled
      trials are needed to establish and justify its use for performing adrenalectomy. 

PMID- 26312213
TI  - Treatment of localized prostate cancer in elderly patients.
AB  - Prostate cancer is a disease of the elderly. According to National Cancer
      Institute, more than 56.7% of incident cases are diagnosed and more than 90% of
      cancer specific deaths occur in men greater than 65 years of age. Despite
      equivalent oncologic outcomes with treatment, primary local therapy is often
      deferred in elderly men with high-risk prostate cancer, in part due to concerns
      that post surgery quality of life (QOL) functional outcomes compare poorly to
      younger men. Our aim in this editorial is to discuss the functional and
      oncological outcomes in management of elderly with localized prostate cancer. 

PMID- 26312214
TI  - Prediction of ipsilateral and contralateral central lymph node metastasis in
      unilateral papillary thyroid carcinoma: a retrospective study.
AB  - BACKGROUND: Prophylactic central lymph node dissection (CLND) in patients with
      papillary thyroid carcinoma (PTC) remains controversial and predictive factors
      for central lymph node (CLN) metastasis in unilateral PTC cases are not well
      defined. The aims of this study were to evaluate the rate of ipsilateral and
      contralateral CLN metastasis and to determine the clinicopathologic factors
      predictive for ipsilateral and contralateral CLN metastasis in unilateral PTC
      cases. METHODS: We retrospectively reviewed 218 PTC patients with clinically
      negative-node neck who have received total thyroidectomy with bilateral CLND.
      Pearson chi(2) test or Fisher exact test and multivariate analysis were used to
      evaluate relationships between CLN metastasis and demographic factors such as
      age, sex and the clinicopathologic factors. RESULTS: Ipsilateral and
      contralateral CLN metastasis were present in 47.7% (104/218) and 13.3% (29/218),
      respectively. Multivariate analysis showed that tumor size (>1 cm) (P=0.016; OR,
      2.005) and age <45 years old (P=0.031; OR, 1.539) were the predictors of
      ipsilateral CLN metastasis, and prelaryngeal lymph node (LN) metastasis (P=0.028;
      OR, 2.970) and ipsilateral CLN metastasis (P<0.001; OR, 15.128) independently
      predicted contralateral CLN metastasis. CONCLUSIONS: CLN metastasis was common in
      PTC patients with clinically node-negative neck and the most common pattern of
      CLN metastasis was ipsilateral CLN metastasis. Prophylactic ipsilateral CLND may
      be an optional procedure and should be considered for patients with a tumor size
      >1 cm. Therapeutic bilateral CLND should be considered in patients with a tumor
      size >1 cm and especially, if there exists prelaryngeal LN or ipsilateral CLN
      metastasis on frozen section analysis.

PMID- 26312215
TI  - Undescended parathyroid adenomas as cause of persistent hyperparathyroidism.
AB  - BACKGROUND: Undescended glands are a rare cause of primary and secondary
      hyperparathyroidism (HPT), but they are more common, however, among patients with
      recurrent HPT or those who have undergone a failed initial cervical exploration.
      The currently development of more precise noninvasive imaging techniques has
      improved the results of preoperative diagnosis of these ectopic lesions. METHODS:
      The operative reports of patients undergoing parathyroidectomy at our institution
      were reviewed to identify patients with an undescended parathyroid gland
      adenomas. Demographic, clinical, imaging and surgical variables were recorded.
      RESULTS: Three patients were included: 2/598 parathyroidectomies performed for
      primary HPT and 1/93 performed for secondary HPT. One case is presented as jaw
      tumor syndrome (JTS). All the patients had undergone at least one operation
      before the definitive focused surgery and represented 6% of our parathyroid
      reoperations. No significant complications and no recurrences were observed in
      the long-term follow up. CONCLUSIONS: Accurate preoperative localization of these
      lesions was possible with noninvasive studies. High cure rate is possible through
      selective approach when accurate preoperative localization. Thorough knowledge of
      parathyroid embryology and meticulous surgical technique are essential,
      particularly in patients with previous unsuccessful explorations.

PMID- 26312216
TI  - A cost analysis of thyroid core needle biopsy vs. diagnostic surgery.
AB  - BACKGROUND: Twenty percent of thyroid fine needle aspiration (FNA) is
      indeterminate. Because 3 in 4 of these are actually benign, a method of
      clarifying the pathology could help patients to avoid diagnostic thyroidectomy.
      Recently, core needle biopsy (CNB) has been proven to be highly reliable for this
      purpose. However, there are no reports of any potential cost benefit provided by
      CNB. Here we analyzed the impact on management costs of CNB compared with
      traditional diagnostic surgery in indeterminate FNA. METHODS: Over 24 months, 198
      patients with thyroid indeterminate cytology underwent CNB at Ospedale
      Israelitico of Rome or diagnostic surgery at the Department of Surgery of
      Sapienza University of Rome. We tabulated costs of the medical instruments,
      operating theater, surgical team, patient recovery, and pathologic examination
      for each method. RESULTS: In CNB group, 42.4% of patients had benign lesions and
      avoided surgery, 20.8% was cancer, and the remaining 36.8% uncertain. The
      malignancy rate in CNB group was 26.4%, and mean cost of CNB per nodule was
      1,032?. In diagnostic surgery group, 24.7% had cancer and 75.3% had benign
      lesions, and mean expense for each thyroidectomy was 6,364?. In an ideal cohort
      of 100 patients with indeterminate FNA, the cost of CNB is 33.8% lower than that
      of diagnostic surgery. CONCLUSIONS: CNB can detect a large proportion of the
      benign thyroid nodules that are classified as indeterminate by FNA. These
      patients can avoid diagnostic thyroidectomy and hospitals can reduce their
      surgical costs by one-third.

PMID- 26312217
TI  - Giant juvenile fibroadenoma: a systematic review with diagnostic and treatment
      recommendations.
AB  - BACKGROUND: Currently, there is a lack of clear guidelines regarding evaluation
      and management of giant juvenile fibroadenomas. The purpose of this study was to
      conduct a systematic review of giant juvenile fibroadenomas and to evaluate the
      most common diagnostic and therapeutic modalities. METHODS: A systematic
      literature search of PubMed and MEDLINE databases was conducted in February 2014
      to identify articles related to giant juvenile fibroadenomas. Pooled outcomes are
      reported. RESULTS: Fifty-two articles (153 patients) met inclusion criteria. Mean
      age was 16.7 years old, with a mean lesion size of 11.2 cm. Most patients (86%)
      presented with a single breast mass. Imaging modalities included ultrasound in
      72.5% and mammography in 26.1% of cases. Tissue diagnosis was obtained using a
      core needle biopsy in 18.3% of cases, fine-needle aspiration (FNA) in 25.5%, and
      excisional biopsy in 11.1% of patients. Surgical treatment was implemented in
      98.7% of patients (mean time to treatment of 9.5 months, range, 3 days to 7
      years). Surgical intervention included excision in all cases, of which four were
      mastectomies. Breast reconstruction was completed in 17.6% of cases. There were
      no postoperative complications. CONCLUSIONS: Diagnosis and treatment of giant
      juvenile fibroadenoma is heterogeneous. There is a paucity of data to support
      observation and non-operative treatment. The most common diagnostic modalities
      include core needle or excisional biopsy. The mainstay of treatment is complete
      excision with an emphasis on preserving the developing breast parenchyma and
      nipple areolar complex. Breast reconstruction is uncommon, but may be necessary
      in certain cases.

PMID- 26312218
TI  - Clinicopathological review of pancreatoblastoma in adults.
AB  - Pancreatoblastoma (PB) is a rare malignant neoplasm of the pancreas with unknown
      etiology. It occurs mostly in the pediatric population with very rare documented
      cases in adults. This is a review of the case reports of the adult
      pancreatoblastoma in the literature. A total of 35 cases were identified and
      reviewed with the mean age of 41 years (range, 18-78 years) and the male sex
      accounted for 51.4% of the cases. Adult Pancreatoblastoma seem to have a
      predilection for the head of the pancreas which accounted for approximately 49%
      of the cases reviewed with an average size of 8 cm (range, 1.8-20 cm). The median
      follow up for patients was 15 months (range, 1-108 months) Metastatic disease and
      local infiltration of surrounding tissues is common with poor prognosis in adult
      patients. Preoperative diagnosis is difficult because of the unhelpful tumor
      markers in adults and the cellular heterogeneity of the tumor which makes fine
      needle aspiration cytology unreliable. Histopathological review of the tumor is
      essential for diagnosis. Pancreatoblastomas should be considered a differential
      diagnosis of solid and cystic pancreatic neoplasms. Surgical resection of the
      tumor is the treatment of choice with a variable combination with radiotherapy
      and chemotherapy. 

PMID- 26312219
TI  - Parathyroid cancer.
AB  - Parathyroid carcinoma is an exceedingly rare endocrine malignancy first described
      in 1933. It accounts for between 0.5% and 5% of all cases of primary
      hyperparathyroidism. Parathyroid carcinoma is unusual among endocrine
      malignancies, being more hormonally active than its benign counterpart.
      Parathyroid carcinoma poses a diagnostic challenge both clinically and
      histologically due to the lack of features which can definitively distinguish
      malignant from benign disease early in its clinical course. Here, we describe the
      clinical features of the disease, and present the current opinion on optimal
      management. Further, we analyse the most recent histological advances made to aid
      in the diagnosis and management of this rare, but potentially devastating,
      disease. 

PMID- 26312220
TI  - Giant benign phyllodes tumor with lactating changes in pregnancy: a case report.
AB  - BACKGROUND: Phyllodes tumor in pregnancy is extremely rare. We present the first
      case ever reported of a giant benign phyllodes tumor with lactating changes
      during pregnancy. PRESENTATION OF CASE: A 36-year-old female patient at the 32nd
      week of pregnancy presented with a huge mass in left breast for 5-6 months.
      Physical examination revealed a firm palpable 20 cm mass occupying the whole left
      breast. Ultrasound guided core needle biopsy demonstrated a fibroepithelial
      lesion suggestive of benign phyllodes tumor. She was scheduled for mastectomy
      three weeks after birth delivery. The microscopic examination of the resected
      specimen revealed the mass consisted mainly of lactating components with areas of
      hypercellular stroma and epithelial proliferation in leaf-like pattern. Finally,
      the pathological report confirmed a giant benign phyllodes tumor with lactating
      changes and frees all surgical margins. DISCUSSION: Phyllodes tumor in pregnancy
      is rare with just nine cases reported. It is unknown if the rapidly growing mass
      in pregnant patient is hormone-dependent. This is the first report of a giant
      benign phyllodes tumor with lactating changes in pregnant patient. In these large
      phyllodes tumors, heterogeneous stromal components are common. It is occasionally
      difficult to distinguish between benign phyllodes tumor with lactating changes
      and lactating adenoma. Because the surgical treatment and local recurrence rate
      are different between these two diseases, we need to clearly differentiate benign
      phyllodes tumors from other benign breast diseases. CONCLUSIONS: This case
      emphasizes the heterogeneity of giant phyllodes tumors. Therefore, it is
      important to thoroughly examine the resected specimen for possible additional
      components. The key point is that adequate and clear surgical margins in any
      phyllodes tumors must be achieved to reduce local recurrence.

PMID- 26312221
TI  - Calcitonin-negative neuroendocrine tumor of thyroid gland mimicking anaplastic
      carcinoma: an unusual entity.
AB  - Medullary thyroid cancer is the neuroendocrine tumor (NET) of thyroid with mostly
      both secreting calcitonin and immunohistochemically showing calcitonin
      positivity. Occasionally; NETs of thyroid may have little or no calcitonin
      expression. We present a case of serum calcitonin negative and
      immunohistochemically calcitonin-negative staining tumor with positive reaction
      to neuroendocrine markers synaptophysin and chromogranin-A. The patient's right
      vocal cord was paralytic and thyroid mass was huge with descending to thorax till
      hilar region. We discussed diagnostic difficulties and way of treatment about
      NETs of thyroid with the light of current literature with this case. 

PMID- 26312222
TI  - Unexpected cause of superior vena cava syndrome.

PMID- 26312223
TI  - Prof. Andrew D. Seidman: new opportunities for improving outcomes for breast
      cancer.

PMID- 26312224
TI  - Biomaterial aspects: A key factor in the longevity of implant overdenture
      attachment systems.
AB  - BACKGROUND: New attachment systems are released for mandibular two-implant
      overdentures often without evidence-based support. Biomaterial aspects are now
      the parameters considered when choosing the appropriate attachment. Studies
      regarding their properties remain scarce. PURPOSE: The purpose of this review was
      to help the clinician in selrcting the most adapted stud attachments according
      evidence-based dentistry. MATERIALS AND METHODS: An electronic search was
      conducted using specific databases (PubMed, Medline, and Elsevier libraries).
      Peer-reviewed articles published in English up to July 2014 were identified.
      Emphasis was given on the biomaterial aspects and technical complications. No
      hand search was added. RESULTS: The electronic search generated 115 full-text
      papers, of which 84 papers were included in the review. The majority were
      clinical and in vitro studies. Some review articles were also considered. Papers
      reported survival and failures of overdenture connection systems. Emphasis was
      laid on attachment deformation. CONCLUSION: Implant overdentures long-term follow
      up studies may provide useful guidelines for the clinician in selecting the type
      of attachment system and overdenture design. Locator attachments are more and
      more used, with lesser complications reported.

PMID- 26312225
TI  - Osteoporosis and jawbones in women.
AB  - Osteoporosis is a major health problem affecting one in three women over the age
      of 50 and may not be detected until fractures occur. Since osteoporotic fractures
      are a health burden worldwide, identifying subjects with a high risk of
      osteoporosis and preventing osteoporosis-related mortality and morbidity are a
      very important health strategy. Women show an estrogen-related bone loss starting
      at menopause, predominantly occurring in trabecular bone. Diagnosis of
      osteoporosis is usually based on the bone mineral density measurement, but this
      is not a practical and economical technique for early detection. Therefore,
      investigators are interested in the possibility of detecting osteoporosis from
      the panoramic radiographs. Mandibular cortical bone undergoes resorptive activity
      in osteoporotic patients, leading to a decreased thickness and more porous
      inferior border. Therefore, studies have demonstrated the usefulness of cortical
      width and shape, determined from panoramic radiographs, in identifying elderly
      individuals with undetected osteoporosis, especially postmenopausal women. In
      conclusion, postmenopausal women with C3 category, Mental Index (MI) <3 mm, and
      panoramic mandibular index (PMI) <0.3 may be considered for further osteoporosis
      investigation. 

PMID- 26312226
TI  - Botulinum toxin for the treatment of hyperfunctional lines of the forehead.
AB  - BACKGROUND: In the 21(st) century, we live longer and a more active life.
      However, while our adult longevity continues to extend, society does not welcome
      a tired and aged appearance. We wish to continue to look as young as possible.
      Most facial rejuvenation techniques such as surgery and injection of collagen,
      silicone, or autogenous fat do not address the fact that these lines are
      functional, i.e. they do not target the cause of hyperfunctional lines: the
      underlying facial mimetic musculature. AIM: To find the efficacy of Botulinum
      toxin for the treatment of hyperfunctional lines of the forehead. MATERIALS AND
      METHODS: The present study consisted of 25 subjects in the age group of 25-65
      years with forehead wrinkles, who visited the Department of Oral and
      Maxillofacial Surgery, CIDS, Virajpet. The materials used for Botulinum toxin
      treatment were Botulinum toxin A, a standard freezer, sterile saline solution,
      alcohol swabs, and insulin syringes with 30 gauge needles. RESULTS: Of the 25
      patients, 21 patients showed satisfactory improvement of their hyperfunctional
      facial lines within 72 h. Maximum improvement was noted in the age group of 25-40
      years, while the older age group of 50-65 years showed less improvement. Maximum
      improvement was seen in type 5 skin, followed by type 4 and type 3 skin. Type 2
      skin showed the least improvement. CONCLUSION: We conclude that Botulinum toxin A
      is a safe and efficacious method of nonsurgically eliminating hyperfunctional
      facial lines of the forehead in the aesthetic patient for a period of 4-6 months.

PMID- 26312227
TI  - Effect of copper-based fungicide (bordeaux mixture) spray on the total copper
      content of areca nut: Implications in increasing prevalence of oral submucous
      fibrosis.
AB  - BACKGROUND: Potentially malignant disorders like oral submucous fibrosis (OSMF)
      often precede oral squamous cell carcinoma (OSCC). The rate of transformation of
      OSMF to OSCC ranges from 3 to 19%. OSMF is etiologically related to chewing of
      areca nut (betel nut), and the high copper content in areca nut plays an
      important role in the pathogenesis of the disorder. Even though many studies
      estimated and confirmed increased copper levels in areca nuts, studies tracing
      the source of the increased copper content are scarce. Interestingly, on review
      of agricultural literature, it was found that most of the areca nut plantations
      in South India commonly use a copper-based fungicide, bordeaux mixture (BM). AIM:
      The aim of the study was to estimate and compare the copper content in areca nuts
      from plantations with and without copper-based fungicide usage. MATERIALS AND
      METHODS: Four areca nut plantations from Dakshina Kannada district, Karnataka
      (group A) and four plantations from Ernakulam district, Kerala (group B) were
      selected for the study. The plantations from Karnataka used copper-based
      fungicide regularly, whereas the latter were devoid of it. Areca nut samples of
      three different maturities (unripe, ripe, and exfoliated) obtained from all
      plantations were dehusked, ground, and subjected to atomic absorption
      spectrometry (AAS) for copper analysis. RESULTS: There was statistically
      significant difference in the copper content of areca nuts from both groups. The
      areca nuts from plantations treated with copper-based fungicide showed
      significantly higher copper levels in all maturity levels compared to their
      counterparts in the other group (P < 0.05). CONCLUSIONS: The high copper content
      in areca nut may be related to the copper-based fungicide treatment on the palms.
      These areca nuts with high copper content used in quid or commercial products may
      be responsible for the increasing prevalence of OSMF.

PMID- 26312228
TI  - Orthodontics as a prospective career choice among undergraduate dental students:
      A prospective study.
AB  - OBJECTIVES: The purposes of this study were to investigate the factors
      influencing the career choice of dental students and to identify the future life
      plans of the students at Prince Sattam Bin Abdulaziz University Dental College
      who had chosen orthodontics as their future specialty. MATERIALS AND METHODS: An
      epidemiological descriptive survey was conducted using a set of questionnaire
      among the second year to fourth year students at Prince Sattam Bin Abdulaziz
      University, Al Kharj, Saudi Arabia. Data were categorized by demographic
      variables and were analyzed with statistical methods using descriptive
      statistical analysis. RESULTS: The most important factor influencing the decision
      to pursue specialty in orthodontics was considering that "orthodontics is
      intellectually challenging" (23%), followed by "previous positive experience"
      (15%). The decision to become an orthodontist was made by 3.7% of the respondents
      in the first year of their course, 44.4% in the second year of their study, 11.1%
      during the third year of their study, 25.9% during the fourth year of their
      study, while none of them had made their decision during the final year of their
      dental school studies. Only one student (3.7) said he planned to work in a
      private college in an academic setting, five students (18.5%) had plans to do
      private practice, two students indicated that they would work for the Ministry of
      Health, while most students (40.7%) reported that they were planning to try a
      combination of all of the above. Six students (22.2%) remained undecided.
      CONCLUSIONS: Majority of the students who had chosen orthodontics as their future
      specialty of choice at Sattam Bin Abdulaziz University Dental College, Saudi
      Arabia had taken up this specialty as they felt that orthodontics was
      intellectually challenging.

PMID- 26312229
TI  - Oral health practices of state and non-state-funded licensed childcare centers in
      Wisconsin, USA.
AB  - OBJECTIVES: To determine whether there is a difference between state-funded
      childcare centers and non-state-funded centers in Wisconsin, USA, with regard to
      their oral health practices. MATERIALS AND METHODS: This is a cross-sectional
      study using an internet-based survey. The participants were licensed childcare
      centers in Wisconsin, USA. Of the 1265 eligible childcare centers invited
      (centers providing day time care to children aged 2-5), 322 chose to participate.
      The main outcome measures were the practice of tooth brushing as a routine
      classroom activity, any educational practice related to oral health, any
      screening and referral practice related to oral health issues, and any practice
      related to dental emergencies. Mediating variables were profit status, center
      location, center affiliation, years of operation, licensed capacity, and child to
      staff ratio. RESULTS: Of the 322 participating centers, 28 centers were
      classified as state-funded and 294 as non-state-funded. Logistic regression
      analysis revealed non-state-funded centers were three times [odds ratio (OR):
      3.01; 95% confidence interval (CI): 1.23, 7.41] more likely to have some kind of
      oral health practice and five times (OR: 5.18; 95% CI: 2.17, 12.50) more likely
      to provide oral health education. However, state-funded centers were five times
      (OR: 5.09; 95% CI: 1.99-13.06) more likely to have tooth brushing as a routine
      classroom activity. CONCLUSION: There is a difference between the oral health
      practices of licensed childcare centers in Wisconsin. An increase in oral health
      practices of state-funded centers is warranted and could make a significant
      difference in the oral health of young children.

PMID- 26312230
TI  - Comparison of the antimicrobial efficacy of chlorhexidine, sodium fluoride,
      fluoride with essential oils, alum, green tea, and garlic with lime mouth rinses
      on cariogenic microbes.
AB  - BACKGROUND: A number of natural mouth rinse formulations are being proposed as an
      alternative to the widely used chemical mouth rinses. OBJECTIVE: To evaluate and
      compare the antimicrobial efficacy of chlorhexidine (0.2%), sodium fluoride
      (0.05%), fluoride with essential oils (0.05%), alum (0.02 M), green tea, and
      garlic with lime mouth rinses against Streptococcus mutans, lactobacilli, and
      Candida albicans. MATERIALS AND METHODS: The three microbes were isolated from
      the saliva samples collected from children with severe early childhood caries.
      The zone of minimum inhibition was assessed using agar diffusion method. The data
      were statistically analyzed using SPSS software. RESULTS: Against S. mutans and
      lactobacilli, chlorhexidine mouth rinse was found to be the most effective as
      compared to sodium fluoride (P < 0.001, P < 0.001), fluoride with essential oils
      (P < 0.001, P < 0.001), alum (P < 0.001, P < 0.001), green tea (P < 0.001, P <
      0.001), and garlic with lime (P < 0.001, P < 0.001) mouth rinses, respectively.
      But against C. albicans, garlic with lime mouth rinse was found to be the most
      effective as compared to chlorhexidine (P < 0.001), sodium fluoride (P < 0.001),
      fluoride with essential oils (P < 0.001), alum (P < 0.001), and green tea (P <
      0.001) mouth rinses. Against S. mutans and lactobacilli, after chlorhexidine
      mouth rinse, garlic with lime mouth rinse was found to be significantly more
      effective than sodium fluoride (P = 0.053, P = 0.001), fluoride with essential
      oils (P < 0.001, P < 0.001), alum (P < 0.001, P < 0.001), and green tea (P <
      0.001, P < 0.001) mouth rinses. CONCLUSION: As a natural mouth rinse, garlic with
      lime mouth rinse was found to be the most promising. However, further studies are
      needed in this field.

PMID- 26312231
TI  - Estimation of plasma fibrinogen degradation products in oral submucous fibrosis:
      A clinico-pathological study.
AB  - BACKGROUND: Oral submucous fibrosis (OSF) is a disease of the oral mucosa
      characterized by excessive accumulation of subepithelial collagen, thereby
      resulting in severe limitation of mouth opening. In OSF, in response to
      inflammation, the body produces more fibrinogen and its degradation products. The
      plasma fibrinogen degradation products (FDP) have been reported to be early
      indicators of fibrin deposition. The present study was intended to ascertain the
      role of FDP in OSF. MATERIALS AND METHODS: A total of 40 subjects were included
      in the study. The subjects for the present study were selected from the
      Department of Oral Medicine and Radiology. The subjects were divided into two
      groups. The study group comprised 24 subjects diagnosed clinically and
      histopathologically as OSF and were further divided into three clinical and
      histological stages of OSF. The control group comprised 16 age- and gender
      matched healthy individuals. Five milliliters of venous blood was drawn from the
      antecubital fossa of all the participants. The blood samples were centrifuged at
      1000 rpm for 5 min to separate plasma, and the plasma FDP levels were assessed.
      RESULTS AND CONCLUSION: There was a significant difference in the plasma FDP
      levels between the study group and the control group. There was a significant
      linear increase of plasma FDP levels with an increase in severity of the clinical
      stage of OSF. Comparison with the histopathological grades of OSF also showed an
      increase in FDP levels with higher grades of OSF and there was a good correlation
      between the clinical staging and the histopathological grading of OSF.

PMID- 26312232
TI  - Assessment of the potential of Allium sativum oil as a new medicament for non
      vital pulpotomy of primary teeth.
AB  - OBJECTIVE: The objective of this study was to compare the clinical and
      radiographic effects of Allium sativum oil and formocresol in nonvital pulpotomy
      in primary teeth. MATERIALS AND METHODS: Twenty children ranging in age from 4 to
      8 years were included in the study. In every one of those children, pulpotomy was
      indicated for the primary molars. Pulpotomy procedure was performed and the
      radicular pulp tissue of one molar was capped with A. sativum oil in a cotton
      pellet while the other molar was capped with formocresol. The teeth were
      evaluated clinically and radiographically before and after 6 months using
      standard clinical and radiographic criteria. Statistically, these results
      revealed significant difference between the radiographic findings of nonvital
      pulpotomy in primary molars with the two medicaments. Statistical analysis was
      performed using independent t-test and paired t-test at the significance level of
      alpha = 0.05. RESULTS: A. sativum oil has potent antibacterial properties that
      enable it to combat intracanal microbes in the infected pulp of primary molars.
      Better results were obtained when A. sativum oil was used. CONCLUSION: A. sativum
      oil had more powerful effects than formocresol on the infected pulp of primary
      nonvital molars.

PMID- 26312233
TI  - Oral hygiene behavior, smoking, and perceived oral health problems among
      university students.
AB  - BACKGROUND: Behavioral aspects play a major role in the prevention of oral
      diseases. Moreover, not many people are aware of the relationship of smoking with
      potential oral diseases. Therefore, the aims of this study were to analyze oral
      hygiene behavior, smoking habits, and perceived oral health problems among a
      sample of university students in Al-Kharj, Saudi Arabia. MATERIALS AND METHODS: A
      self-administered questionnaire about oral hygiene behavior, smoking, and
      perceived oral health problems was developed. The questionnaires were mainly
      distributed in Medical, Dental, and Pharmacy colleges of the university.
      Questionnaires completed at other colleges were included under the term "other
      colleges." RESULTS: Overall, 380 questionnaires were returned. Majority of the
      students (92.4%) reported cleaning their teeth. Most of the students reported
      cleaning teeth once daily (48.7%). Just over a half (55.8%) reported having a
      dental check-up in the last 6 months, and a significantly higher number of dental
      students reported having a dental check-up (P < 0.05). Regarding smoking, the
      majority (63.4%) reported to have never smoked while 17.3% reported that they
      were smoking frequently. About 17.6% perceived oral health problems, including a
      significant proportion of those who reported frequent smoking. CONCLUSIONS: Oral
      hygiene behavior exhibited by the university students sample was similar.
      Majority cleaned their teeth, although only once. Smoking habit was not exhibited
      by the vast majority of students. Frequent smokers perceived oral health problems
      more than other students.

PMID- 26312234
TI  - Practicing quality nephropathology in a developing country; challenges and
      solutions.

PMID- 26312235
TI  - Colonization and antifungals susceptibility patterns of Candida species isolated
      from hospitalized patients in ICUs and NICUs.
AB  - BACKGROUND: Several studies have shown that there are an increasing in invasive
      candidiasis during 2-3 last decades. Although, Candida albicans is considered as
      the most common candidiasis agents, other non-albicans such as C. glabrata, C.
      krusei, C. parapsilosis, and C. tropicalis were raised as infectious agents.
      Resistance to fluconazole among non-albicans species is an important problem for
      clinicians during therapy and prophylaxis. OBJECTIVES: The aim of current study
      was to detect the Candida species from hospitalized neonatal and children in
      intensive care units (ICUs) and neonatal intensive care units (NICUs). In
      addition, the susceptibility of isolated agents were also evaluated against three
      antifungals. MATERIALS AND METHODS: In the present study 298 samples including 98
      blood samples, 100 urines and 100 swabs from oral cavity were inoculated on
      CHROMagar Candida. Initial detection was done according to the coloration
      colonies on CHROMagar Candida . Morphology on cornmeal agar, germ tube formation
      and growth at 45 degrees C were confirmed isolates. Amphotericin B, fluconazole
      and terbinafine (Lamisil) were used for the susceptibility tests using
      microdilution method. RESULTS: In the present study 21% and 34% of urines and
      swabs from oral cavity were positive for Candida species, respectively. The most
      common species was C. albicans (62.5%) followed by C. tropicalis (15.6%), C.
      glabrata (6.3%) and Candida species (15.6%). Our study indicated that the most
      tested species of Candida, 70.3% were sensitive to fluconazole at the
      concentration of <=8 MUg/mL. Whereas 9 (14.1%) of isolates were resistant to
      amphotericine B at >=8 MUg/mL. CONCLUSIONS: This study demonstrates the
      importance of species identification and antifungals susceptibility testing for
      hospitalized patients in ICUs and NICUs wards.

PMID- 26312236
TI  - The association between blood pressure level and serum uric acid concentration in
      hemodialysis patients.
AB  - BACKGROUND: High blood pressure is a common condition in hemodialysis patients.
      Uric acid, which is high in these patients due to decreased clearance, had been
      shown to positively correlate with blood pressure in animal studies. OBJECTIVES:
      The goal of this investigation was to evaluate the impact of high uric acid level
      on blood pressure in these patients. PATIENTS AND METHODS: Ninety-one patients,
      on three times weekly hemodialysis, were studied. Uric acid levels were measured
      just before and after hemodialysis along with blood pressures before, during and
      after each session. Data were analyzed by SPSS 15. A P value less than 0.05 was
      considered significant. RESULTS: 40 (44%) of patients had serum uric acid >=6
      mg/dl. Before dialysis 51 (61%) and 19 (21%) had high systolic blood and
      diastolic blood pressures respectively. Also, 50 (55%) were with wide pulse
      pressure and 63 (69%) had high mean arterial pressure (MAP). Additionally 62
      (68%) developed inter-dialysis hypotension. After measuring odds ratio for
      hyperuricemia in each group, we observed low risk of hypruricemia in the group
      with high systolic pressure (OR = 0.352; 95% CI: 0.147-0.844; P = 0.01), the high
      MAP group (OR = 0.382; 95% CI: 0.153-0.955; P = 0.03) and wide pulse pressure
      group (OR = 0.416; 95% CI: 0.177-0.975; P = 0.04). There was no association
      between high uric acid level and diastolic pressure (P = 0.11) and inter-dialysis
      hypotension (P = 0.33). No relationship was found between serum uric acid and
      KT/V (P = 0.2), normalized protein catabolic rate (nPCR) (P = 0.07) and body mass
      index (BMI) (P = 0.4). CONCLUSIONS: This study showed paradoxical association
      between high uric acid level and high systolic pressure, high MAP and wide pulse
      pressure and these effects were independent of dialysis duration, dialysis
      efficacy and nutrition, assuming that these relationships could be due to reverse
      epidemiology in dialysis patients.

PMID- 26312237
TI  - Clinical and biochemical investigation of male patients exhibiting membranous
      cytoplasmic bodies in biopsied kidney tissues; a pitfall in diagnosis of Fabry
      disease.
AB  - BACKGROUND: The existence of membranous cytoplasmic bodies in biopsied kidney
      tissues is one of the important findings when considering Fabry disease as the
      first choice diagnosis. However, there are possible acquired lysosomal diseases
      associated with pharmacological toxicity, although less attention has been paid
      to them. CASE PRESENTATION: We experienced 3 male patients presenting with
      proteinuria and specific pathological changes strongly suggesting Fabry disease.
      We sought detailed clinical and biochemical information to avoid a wrong
      diagnosis. The patients were examined clinically and pathologically, and plasma
      alpha-galactosidase A (GLA) activity and the globotriaosylsphingosine (lyso-Gb3)
      concentrations were measured. Electron microscopic examination revealed numerous
      membranous inclusion bodies in podocytes, and biochemical analysis revealed
      normal GLA activity and a normal lyso-Gb3 level in plasma, showing that they did
      not have Fabry disease. They suffered from hyperlipidemia, myeloma, or lupus
      nephritis. They had received pitavastatin calcium, clarithromycin, loxoprofen
      and/or prednisolone, and there was no medication history of cationic amphiphilic
      drugs. CONCLUSIONS: In this case series, the etiology of the inclusions was not
      clarified. However, these cases indicate that careful attention should be paid on
      diagnosis of patients exhibiting inclusion bodies in kidney cells, and it is
      important to confirm their past and present illnesses, and medication history as
      well as to measure the GLA activity and lyso-Gb3 level.

PMID- 26312238
TI  - Histiocytic sarcoma; case report of a rare disease in a kidney transplant
      recipient.
AB  - BACKGROUND: Histiocytic sarcoma (HS) is a rare hematologic neoplasm with a few
      hundred cases having been described to date. CASE PRESENTATION: We report the
      case of a 56-year-old woman with a history of hepatitis C infection and chronic
      kidney disease (CKD), submitted to a kidney transplant in 1984, under maintenance
      immunosuppression with prednisone and azathioprine. Patient presented with a
      relentlessly growing mass on her right front thorax. It was painless, smooth, and
      adherent to the deep muscle. Laboratory studies were unremarkable.
      Ultrasonography and computerized tomography (CT) scan revealed a highly
      vascularized heterogeneous mass (8*9 cm), with a necrotic centre. Positron
      emission tomography (PET) scan demonstrated multiple thoracic, abdominal, and
      pelvic nodules. Histology revealed a highly undifferentiated HS (vimentin, CD68,
      CD99, and CD4 positive). In spite of having started treatment with etoposide and
      thalidomide, no clinical response was achieved and the patient died three months
      later. CONCLUSIONS: To the authors' knowledge, this is the first described case
      of HS in a solid organ transplant patient.

PMID- 26312239
TI  - Early onset nephrotic syndrome with dysmorphic facies and microcephaly.

PMID- 26312241
TI  - The diversity of retinoid biology.

PMID- 26312240
TI  - FUNCTIONAL LIMITATIONS AND ADIPOKINES IN HIV-INFECTED OLDER ADULTS.
AB  - BACKGROUND: There is a significant increase in the number of HIV-infected older
      adults (HOA). This population may experience functional decline at a much younger
      age. Little is known about the relationship between functional limitations and
      systemic adipokines in HOA. OBJECTIVE: Our study aimed to evaluate the
      relationship between functional limitations and systemic adipokine levels in HOA
      population. DESIGN: Cross-sectional. SETTING: Academic hospital-based infectious
      disease clinic. PARTICIPANTS: The study investigated community-dwelling HIV
      infected adults >50 years old and compared this group with age, gender and BMI
      comparable healthy controls. MEASUREMENTS: We measured functional status, body
      composition and plasma concentrations of adipokines. RESULTS: Fifty-four HOA were
      studied (mean: age 57 years, BMI 29 kg/m2, CD4 604, duration of HIV 17 years) and
      compared with thirty-two age, gender and BMI comparable healthy controls. The HOA
      group showed significantly higher functional limitations compared to the age,
      gender and BMI comparable controls (p<0.05). Levels of adipokines were
      significantly different between the two groups (p<0.05). Multiple regression
      analyses indicated that adiponectin and visfatin were significantly correlated
      with several physical function measures after controlling for age, sex, and
      metabolic comorbidities. Adiponectin was negatively correlated with functional
      limitations, and this relationship was stronger in the control group compared to
      the HOA group. Conversely, visfatin was positively correlated with functional
      limitations only in the HOA group. CONCLUSION: HOA have significant functional
      limitations and alteration in adipokine levels compared to controls. Adiponectin
      and visfatin were associated with functional limitations. Visfatin was a
      correlate of physical function only in the HOA group. Prospective longitudinal
      studies could provide further insight on the role of adipokines in HIV-related
      functional decline.

PMID- 26312242
TI  - STRA6: role in cellular retinol uptake and efflux.
AB  - Distribution of vitamin A throughout the body is important to maintain retinoid
      function in peripheral tissues and to ensure optimal vision. A critical step of
      this process is the transport of vitamin A across cell membranes. Increasing
      evidence indicates that this process is mediated by a multidomian membrane
      protein that is encoded by the stimulated by retinoic acid 6 (STRA6) gene.
      Biochemical studies revealed that STRA6 is a transmembrane pore which transports
      vitamin A bidirectionally between extra- and intracellular retinoid binding
      proteins. Vitamin A accumulation in cells is driven by coupling of transport with
      vitamin A esterification. Loss-of-function studies in zebrafish and mouse models
      have unraveled the critical importance of STRA6 for vitamin A homeostasis of
      peripheral tissues. Impairment in vitamin A transport and uptake homeostasis are
      associated with diseases including type 2 diabetes and a microphthalmic syndrome
      known as Matthew Wood Syndrome. This review will discuss the advanced state of
      knowledge about STRA6's biochemistry, biology and association with disease. 

PMID- 26312243
TI  - Alcohol exposure in utero perturbs retinoid homeostasis in adult rats.
AB  - BACKGROUND: Maternal alcohol exposure and adult alcohol intake have been shown to
      perturb the metabolism of various micro- and macro-nutrients, including vitamin A
      and its derivatives (retinoids). Therefore, it has been hypothesized that the
      well-known detrimental consequences of alcohol consumption may be due to
      deregulations of the metabolism of such nutrients rather than to a direct effect
      of alcohol. Alcohol exposure in utero also has long-term harmful consequences on
      the health of the offspring with mechanisms that have not been fully clarified.
      Disruption of tissue retinoid homeostasis has been linked not only to abnormal
      embryonic development, but also to various adult pathological conditions,
      including cancer, metabolic disorders and abnormal lung function. We hypothesized
      that prenatal alcohol exposure may permanently perturb tissue retinoid
      metabolism, predisposing the offspring to adult chronic diseases. METHODS: Serum
      and tissues (liver, lung and prostate from males; liver and lung from females)
      were collected from 60-75 day-old sprague dawley rats born from dams that were:
      (I) fed a liquid diet containing 6.7% alcohol between gestational day 7 and 21;
      or (II) pair-fed with isocaloric liquid diet during the same gestational window;
      or (III) fed ad libitum with regular rat chow diet throughout pregnancy. Serum
      and tissue retinoid levels were analyzed by reverse-phase high-performance liquid
      chromatography (HPLC). Serum retinol-binding protein (RBP) levels were measured
      by western blot analysis, and liver, lung and prostate mRNA levels of lecithin
      retinol acyltransferase (LRAT) were measured by qPCR. RESULTS: Retinyl ester
      levels were significantly reduced in the lung of both males and females, as well
      as in the liver and ventral prostate of males born from alcohol-fed dams. Tissue
      LRAT mRNA levels remained unchanged upon maternal alcohol treatment. CONCLUSIONS:
      Prenatal alcohol exposure in rats affects retinoid metabolism in adult life, in a
      tissue- and sex-dependent manner. We propose that the alcohol-induced
      perturbations of vitamin A metabolism may predispose to detrimental consequnces
      on adult health.

PMID- 26312244
TI  - Obesity, the deadly quartet and the contribution of the neglected daily organ
      rest - a new dimension of un-health and its prevention.
AB  - The "deadly quartet": excessive weight, hypertension, impaired glucose
      homeostasis, and atherogenic dyslipidemia constitute a greater threat to health
      than the added effects of smoking and alcohol abuse. It is strongly associated
      with unrestricted consumption of processed, refined foods. Recent observations
      from experience in South East Asia shows that the interval between lifestyle
      changes and associated change in disease pattern is shorter than earlier
      believed. Recent experience from obesity studies in Africa demonstrates not only
      dramatic changes in health but also large social consequences from being
      overweight. Obesity is not only a result of overeating - dozens of other factors
      are known to contribute. Our palaeolithic forefathers and those living a similar
      lifestyle today are reported to rarely have diseases and to live a long life. One
      such group is the Hunzas, living in Northern Pakistan, are reported to live on a
      daily 1,800-calorie 99% plant-based diet, consisting in 73% of mostly
      unrefined/unprocessed carbohydrates, 17% fat and 10% protein. They, and most
      likely also our forefathers, do/did most likely only eat twice a day, at noon and
      early evening. Calorie-restriction (CR) and also fasting was early recommended
      and has been so during thousands of years - early Greek medicine and giants such
      as Hippocrates, Galenus and later also Paracelsus prescribed restrictions in
      eating and fasting. So did Middle Age physicians and other nutrition experts such
      as Louis Cornado. Today it is again practiced around the World. Overeating and
      heavy postprandial metabolism is a great burden to the body causing elevated
      levels in blood of endotoxin, increased inflammatory and oxidative stress,
      release of tumor necrosis factor-alpha, and other pro-inflammatory cytokines,
      increases in numbers of and activating of leukocytes, a reaction that is
      potentiated by the presence of large-chain fatty acids and sugars. Various
      metabolic, uremic, microbiota-derived and environmental poisons accumulate in
      large amounts in the adipose tissues. High levels of poisons in the adipose
      tissues decreases the turnover of fats in order to protect other organs. The
      content in adipose of POPs - altogether 17 dioxins/furans and 18 polychlorinated
      biphenyl congeners, has been reported to be 2-3 times higher in obese compared to
      lean persons. Daily fasting consisting in 16 to 18 hours of avoidance of calorie
      intake offers an interesting alternative. An attractive policy is to abstain from
      eating between 18:00 in the evening and 10:00 or 12:00 AM, a plan, which I
      personally have practiced during many years. 

PMID- 26312245
TI  - Intestinal microbial metabolism of phosphatidylcholine: a novel insight in the
      cardiovascular risk scenario.
AB  - Intestinal microbiota is a "dynamic organ" influencing host metabolism,
      nutrition, physiology and immune system. Among its several interactions, the role
      of a phosphatidylcholine metabolite derived by gut flora activity, i.e.,
      trimethylamine-N-oxide (TMAO), allows perceiving a novel insight in the
      cardiovascular risk scenario, being a strong predictor of this condition. Based
      on current reports, including the paper of Tang et al., we describe here: the
      possible role of intestinal microbiota in cardiovascular risk as well as
      potential interventions to reduce gut flora TMAO production by diet, probiotics
      and antibiotics. Finally, we highlight the possibility of evaluating, monitoring
      and modulating TMAO in order to use its serum levels as a marker of
      cardiovascular risk in the next future, when the need of controlled studies on
      large series will be satisfied. 

PMID- 26312246
TI  - Wading through the noise of "multi-omics" to identify prognostic biomarkers in
      hepatocellular carcinoma.
AB  - Multi-omics, the molecular analysis of genes, transcriptional RNA and proteins,
      allows researchers document the mechanism of action of a target gene. However
      multi-omics may result in an avalanche of information when used to screen a
      population. It is very difficult to discern a pattern or signal related to a
      disease or its progression. Differential multi-omics exploits our ability to see
      differences between subjects who are similar in all respects except for the
      outcome being tested. Twin studies are an example of this. Miao and colleagues
      compared two patients who had diverse outcomes following treatment of multi-focal
      hepatocellular carcinoma (HCC) to identify seven candidates as the responsible
      genes. In a larger cohort of patients with HCC they narrowed the field down to a
      single target down. By looking at progression of HCC, they isolated TTK, a
      protein kinase which disrupts the interaction of the tumour suppressor p53 with
      the oncogene MDM2. TTK-high tumours recurred 3 times faster than TTK-low tumours.

PMID- 26312247
TI  - Oesophagogastric junction stricture: a rare complication of chemotherapy for
      malignant lymphoma.

PMID- 26312248
TI  - Undifferentiated (embryonal) sarcoma of liver.

PMID- 26312249
TI  - Antibiotic regimens for treatment of infections due to multidrug-resistant Gram
      negative pathogens: An evidence-based literature review.
AB  - Evidences regarding the efficacy of different antibiotic regimens proposed for
      treatment of multidrug-resistant (MDR) Gram-negative pathogens have been
      reviewed. Available data in Scopus, Medline, EMBASE, the Cochrane central
      register of controlled trials, and Cochrane database of systematic reviews have
      been collected. Several antibiotic regimens are proposed for treatment of MDR
      Gram-negative infections (defined as nonsusceptibility to at least one agent in
      three or more antimicrobial categories). The most challenging issue is the
      treatment of carbapenem-resistant (CR) Gram-negative pathogens. A carbapenem plus
      either colistin or tigecycline was the most effective regimen for treatment of CR
      Gram-negative pathogens with low-level resistance (minimal inhibitory
      concentration [MIC] <= 8 mg/L). However, in high-level resistance (MIC > 8 mg/L),
      combination of colistin and tigecycline showed promising effect. 

PMID- 26312250
TI  - A review of pharmaceutical policies in response to economic crises and sanctions.
AB  - An economic crisis has been defined as a situation in which the scale of a
      country's economy becomes smaller in a period of time. Economic crises happen for
      various reasons, including economic sanctions. Economic crises in a country may
      affect national priorities for investment and expenditure and reduce available
      resources, and hence may affect the health care sector including access to
      medicines. We reviewed the pharmaceutical policies that the countries adopted in
      order to mitigate the potential negative effects on access to medicines. We
      reviewed published reports and articles after conducting a comprehensive search
      of the PubMed and the Google Scholar. After extracting relevant data from the
      identified articles, we used the World Health Organization (WHO) access to
      medicines framework as a guide for the categorization of the policies. We
      identified a total of 40 studies, of which 10 reported the national
      pharmaceutical policies adopted to reduce the negative impacts of economic crises
      on access to medicines in high-income and middle-income countries. We identified
      89 policies adopted in the 11 countries and categorized them into 12 distinct
      policy directions. Most of the policies focused on financial aspects of the
      pharmaceutical sector. In some cases, countries adopted policies that potentially
      had negative effects on access to medicines. Only Italy had adopted policies
      encompassing all four accesses to medicine factors recommended by the WHO. While
      the countries have adopted many seemingly effective policies, little evidence
      exists on the effectiveness of these policies to improve access to medicines at a
      time of an economic crisis. 

PMID- 26312251
TI  - Provision of pharmaceutical care in patients with limited English proficiency:
      Preliminary findings.
AB  - OBJECTIVE: Overcoming language and cultural barriers is becoming ever challenging
      for pharmacists as the patient population grows more ethnically diverse. To
      evaluate the current practices used by the pharmacists for communicating with
      patients with limited English proficiency (LEP) and to assess pharmacists'
      knowledge of, attitude toward, and satisfaction with accessing available services
      for supporting LEPs patients within their current practice settings. METHODS:
      Semi-structured interviews were conducted with five pharmacists employed in
      pharmacies representing multiple practice settings Queensland, Australia.
      Thematic analysis was primarily informed by the general inductive approach. NVivo
      software (QSR International Pty Ltd.) was used to manage the data. FINDINGS:
      Three interlinked themes emerged from the analysis of interview data: (1)
      Barriers to the provision of pharmaceutical care, (2) Strategies employed in
      dealing with LEP patients, and (3) Lack of knowledge about existing services.
      Pharmacists recognized their lack of skills in communicating with LEP patients to
      have potential negative consequences for the patient and discussed these in terms
      of uncertainty around eliciting patient information and the patient's
      understanding of their instructions and or advice. Current strategies were
      inconsistent and challenging for LEP patient care. While the use of informal
      interpreters was common, a significant degree of uncertainty surrounded their
      actual competency in conveying the core message. CONCLUSION: The present study
      highlights a significant gap in the provision of pharmaceutical care in patients
      with LEP. Strategies are needed to facilitate quality use of medicines among this
      patient group.

PMID- 26312252
TI  - Effect of Omega-3 fatty acids on blood pressure and serum lipids in continuous
      ambulatory peritoneal dialysis patients.
AB  - OBJECTIVE: Hypertension and hyperlipidemia are two major risk factors for
      cardiovascular disease in continuous ambulatory peritoneal dialysis (CAPD)
      patients. This study was designed to investigate the effect of omega-3 fatty
      acids on blood pressure (BP) and serum lipids in CAPD patients. METHODS: This
      study was a randomized double-blind clinical trial in which 90 CAPD patients were
      randomly assigned to either the omega-3 or the placebo group. Patients in omega-3
      group received 3 g/day omega-3 for 8 weeks, whereas patients in the control group
      received placebo. At baseline and at the end of 8 weeks, the patients' BP was
      controlled, and serum biochemistry was measured. FINDINGS: Mean systolic BP
      decreased (-22.2 +/- 14.2 mmHg) in the omega-3 group at the end of the study
      while in the placebo group increased (+0.5 +/- 30.2 mmHg) (P < 0.0001). Mean
      diastolic BP of the omega-3 group decreased more (-11.95 +/- 11.9 mmHg) comparing
      with the placebo group (-1.1 +/- 17.3 mmHg) (P = 0.001). There were no
      significant differences between the two groups in mean changes in serum
      triglyceride, and total, high-density lipoprotein, and low-density lipoprotein
      cholesterol. CONCLUSION: The results of this study indicate that omega-3 reduced
      BP significantly but had no effect on lipid profile in our CAPD patients.

PMID- 26312253
TI  - Premedication dilemmas, is Pregabalin the answer?
AB  - OBJECTIVE: Laryngoscopy and intubation are associated with sympathetic
      stimulation which can prove deleterious in patients with cardiovascular
      compromise; so, various methods have been tried to obtund this pressor response.
      In this study, we have assessed the efficacy of pregabalin in attenuating the
      pressor response to laryngoscopy and intubation. METHODS: This prospective
      randomized study included 80 patients with American Society of Anesthesiologists
      physical status grades I-II, in the age group of 18-60 years of age. The patients
      were randomized into two groups of 40 patients each. Group A received the placebo
      orally, 90 min prior to surgery. Group B received 150 mg of pregabalin orally, 90
      min prior to surgery. These patients were assessed in terms of sedation with
      Ramsay sedation scale (RSS). In the operation theatre, the heart rate (HR),
      systolic blood pressure, diastolic blood pressure, mean arterial pressure, and
      oxygen saturation recorded at baseline and 1, 3, 5, and 10 min after intubation.
      The rate pressure product (RPP) was calculated for these time intervals. In the
      postoperative period, patients were assessed for complications like dizziness,
      nausea, and blurred vision. Statistical analysis was performed using Chi-square
      and ANOVA tests. FINDINGS: The group receiving 150 mg of pregabalin as
      premedication was found to be adequately sedated at 1 h post-premedication with
      52% patients having a RSS score of 3 compared to 4% with the same RSS score in
      the placebo group (P < 0.0001). Hemodynamics was more stable post-intubation with
      significant stability in the HR (P = 0.002) and RPP (P = 0.004) in the pregabalin
      group. CONCLUSION: Pregabalin when given as a premedication provides adequate
      sedation and obtunds the pressor response seen with intubation.

PMID- 26312254
TI  - Medication errors in oral dosage form preparation for neonates: The importance of
      preparation technique.
AB  - OBJECTIVE: Considering the inability of neonates to swallow oral drugs in the
      form of solid tablets, the lack of appropriate dosage forms for infants, and the
      necessity to prepare some pills for neonates, the current study investigated
      dosage accuracy in drugs for neonates prepared from tablets by analyzing the
      concentrations of final products. METHODS: Captopril and spironolactone, oral
      dosage forms that are not suitable for infants, were chosen as the drug model for
      this study. Demographic characteristics of nurses providing medications and
      tablet preparation methods were documented in a random observational method. To
      determine concentrations of final solutions, 120 drug samples (60 captopril and
      60 spironolactone samples) prepared by Neonatal Intensive Care Unit nurses of the
      Children Cure and Health Hospital of Tabriz University of Medical Sciences were
      analyzed using high performance liquid chromatography (HPLC) and
      spectrophotometry. FINDINGS: There was a significant error rate in the
      concentration of captopril in prepared solutions compared with the ordered
      dosage. No differences were observed in the demographic characteristics of the
      nurses and the method of preparation between the two drugs. The only difference
      related to the preparation technique was that in most cases (70.8%), one whole
      spironolactone tablet was used, whereas in around 50% of samples in captopril
      group, half or a quarter of one captopril tablet was utilized for the intended
      dosage (P = 0.009). CONCLUSION: This research suggests that the use of a whole
      tablet instead of a divided tablet in the manual preparation of medication dosage
      forms for neonates is the most appropriate approach.

PMID- 26312255
TI  - Antimicrobial susceptibility pattern of extended-spectrum beta- lactamase
      producing Klebsiella pneumoniae clinical isolates in an Indian tertiary hospital.
AB  - OBJECTIVE: There is an increased prevalence of extended-spectrum beta-lactamase
      producing Klebsiella pneumoniae (ESBL-KP) worldwide including India, which is a
      major concern for the clinicians, especially in intensive care units and
      pediatric patients. This study aims to determine the prevalence of ESBL-KP and
      antimicrobial sensitivity profile to plan a proper hospital infection control
      program to prevent the spread of resistant strains. METHODS: KP isolates obtained
      from various clinical samples were evaluated to detect the production of ESBL by
      phenotypic methods. Antimicrobial susceptibility profile was also determined of
      all the isolates. FINDINGS: Of 223 nonduplicate isolates of K. pneumoniae, 114
      (51.1%) were ESBL producer and antimicrobial susceptibility profile showed the
      isolates were uniformly sensitive to imipenem and highly susceptible to beta
      lactamase inhibitor combination drugs (67-81%) and aminoglycosides (62-76%), but
      less susceptible to third generation cephalosporins (14-24%) and non-beta-lactam
      antibiotics such as nitrofurantoin (57%), fluoroquinolones (29-57%), piperacillin
      (19-23%), and aztreonam (15-24%). CONCLUSION: This study found that beta
      lactamase inhibitor combinations are effective in treatment of such infections
      due to ESBL-KP thus these drugs should be a part of the empirical therapy and
      carbapenems should be used when the antimicrobial susceptibility tests report
      resistance against inhibitors combinations.

PMID- 26312256
TI  - The efficacy of different doses of Midazolam added to Lidocaine for upper
      extremity Bier block on the sensory and motor block characteristics and
      postoperative pain.
AB  - OBJECTIVE: This study was designed to evaluate the effect of different doses of
      midazolam on anesthesia and analgesia quality when added to lidocaine during the
      intravenous regional anesthesia (IVRA). METHODS: One hundred and forty patients
      underwent hand surgery were randomly allocated into four groups to receive 3
      mg/kg lidocaine 2% diluted with saline to a total volume of 40 mL in the control
      Group L-C (n = 35), 30 MUg/kg midazolam plus 3 mg/kg lidocaine 2% diluted with
      saline to a total volume of 40 mL in the midazolam Group L-M1 (n = 35), 40 MUg/kg
      midazolam plus 3 mg/kg 2% lidocaine diluted with saline to a total volume of 40
      mL in the midazolam Group L-M2 (n = 35), and 50 MUg/kg midazolam plus 3 mg/kg
      lidocaine 2% diluted with saline to a total volume of 40 mL in the midazolam
      Group L-M3 (n = 35). Sensory and motor block and recovery times, tourniquet pain,
      intra-operative analgesic requirement, and visual analog scale (VAS) scores were
      recorded. FINDINGS: Onset time of sensory and motor block in L-M3 Group was
      shorter than the L-M2 and L-M1 and L-C Groups (P < 0.001). Furthermore, prolonged
      sensory (P = 0.005) and motor recovery time (P = 0.001) in L-M3 were longer than
      the other groups. Intra-operative VAS score and intra-operative fentanyl
      consumption in L-M3 were lower than the other groups (P < 0.001). The numbers of
      patients needed to pethidine in Group L-M3 were significantly less compared with
      the other groups (P = 0.035). VAS scores were significantly lower in Group L-M3
      in different time intervals in the postoperative period compared with the other
      groups (P < 0.001). CONCLUSION: Addition of 50 MUg/kg midazolam for IVRA (Group L
      M3) enhanced intra-operative analgesia and improved anesthesia quality better
      than other groups receiving lower midazolam doses as well as a control group.

PMID- 26312258
TI  - High resolution ion mobility-mass spectrometry for separation and identification
      of isomeric lipids.
AB  - Lipidomics is a particularly difficult analytical challenge due to the number and
      importance of isomeric species that are known or postulated in biological
      samples. Current separation and identification techniques are too often
      insufficiently powerful, slow or ambiguous. High resolution, low field ion
      mobility coupled to mass spectrometry is shown here to have sufficient
      performance to represent a new alternative for lipidomics. For the first time,
      drift-tube ion mobility separation of lipid isomers that differ only in position
      of the acyl chain, position of the double bond or double bond geometry is
      demonstrated. Differences in collision cross sections of less than 1% are
      sufficient for baseline separation. The same level of performance is maintained
      in complex biological mixtures. More than 130 high-precision reduced mobility and
      collision cross section values were also determined for a range of lipids. Such
      data can be the basis of a new lipidomics workflow, as the appropriate libraries
      are developed. 

PMID- 26312257
TI  - Outcome of treatment in patients with methamphetamine poisoning in an Iranian
      tertiary care referral center.
AB  - OBJECTIVE: Methamphetamine is the second most widely abused drug worldwide. We
      performed a study on the treatment outcome of acute methamphetamine intoxication
      in a referral tertiary care University hospital in Iran. METHODS: In this
      hospital-based, retrospective study which was carried out from 2012 to 2013,
      medical records of all patients aged 18 to 65 years who were admitted with a
      reliable history and clinical diagnosis of acute methamphetamine intoxication
      were abstracted and analyzed. Patients' data included gender, age, type and route
      of poisoning, clinical manifestations, duration of hospitalization, and the
      treatment outcome. ANOVA, Chi-square, and binary logistic regression statistical
      tests were used for data analysis. FINDINGS: A total of 129 patients with a mean
      age of 30.70 +/- 0.93 (mean +/- standard error), including 111 (86%) males, had
      been fully evaluated. Most of the patients had intentional poisoning (93.7%). In
      42.6% of patients, inhalation was the main route of exposure. Most of the
      patients had complete improvement without any complication (89.1%). Age (odds
      ratio [OR], 1.05; 95% confidence interval [95% CI] 1.006-1.099), suicide history
      (OR, 30.33; 95% CI 3.11-295.24), route of poisoning ([ingestion: OR, 0.21; 95% CI
      0.05-0.87], [inhalation: OR, 0.19; 95% CI 0.04-0.78]), and pulmonary system
      manifestations (OR 1.84; 95% CI 1.15-2.93) were predictive in patients outcome (P
      < 0.05). CONCLUSION: Methamphetamine poisoning was more common in males with
      intentional poisoning. Age, past history of suicide, route of poisoning, and
      pulmonary manifestations on admission could be considered as important predictive
      factors in patients' outcome.

PMID- 26312259
TI  - Determination of metal ion concentrations by SERS using 2,2'-bipyridyl complexes.
AB  - Surface enhanced Raman scattering (SERS) can generate characteristic spectral
      "fingerprints" from metal complexes, thus providing the potential for the
      development of methods of analysis for the identification and quantitation of a
      range of metal ions in solution. The advantages include sensitivity and the use
      of one ligand for several metals without the need for a specific chromophore.
      Aqueous solutions of Fe(II), Ni(II), Zn(II), Cu(II), Cr(III) and Cd(II) in the
      presence of excess 2,2'-bipyridyl (bipy) were analysed using SERS. Specific
      marker bands enabled the identification of each metal ion and the limit of
      detection for each metal ion was estimated. Two of the ions, Zn(II) and Cu(II),
      could be detected below the World Health Organisation's (WHO) recommended limits
      for drinking water at levels of 0.22 and 0.6 mg L(-1), respectively.

PMID- 26312260
TI  - Several hundred-fold enhanced fluorescence from single fluorophores assembled on
      silver nanoparticle-dielectric-metal substrate.
AB  - We observed over 400-fold enhanced fluorescence from single Cy5 molecules
      assembled on multilayer silver nanoparticle-dielectric-metal (PDM) substrate.
      This substantial enhancement is due to the near-field enhanced excitation,
      emission, and interaction of Cy5 with plasmonic nanostructures. Experimental
      observation is supported by finite-element method calculations. 

PMID- 26312261
TI  - Status of Diabetes Care: New Challenges, New Concepts, New Measures--Focusing on
      the Future!

PMID- 26312262
TI  - Natural Products From Marine Algae. Preface.

PMID- 26312263
TI  - Reply from the Author.

PMID- 26312264
TI  - Intraosseous access to the circulatory system: An under-appreciated option for
      rapid access.
AB  - In many emergency situations rapid vascular access is a priority, particularly in
      cases involving haemodynamic compromise. Traditional vascular access through the
      use of an intravenous cannula, although the preferred first line method, can in
      certain circumstances have a high rate of failure. A study by Minville et al
      (2006) showed that the success rate of first attempt venous cannulation can be as
      low as 76%. Repeated attempts at venous cannulation in patients with difficult
      vascular access wastes valuable time which in some situations could prove fatal.

PMID- 26312265
TI  - A re-assessment of Konarus Bamber, 2006 and sympatric leptocheliids from
      Australasia, and of Pseudoleptochelia Lang, 1973 (Crustacea: Peracarida:
      Tanaidacea).
AB  - Following recent revelations regarding males with subchelate chelipeds in the
      tanaidacean genus Parakonarus, a number of Australian leptocheliid taxa are re
      assessed, and their males and females variously re-allocated. To assist the
      interpretation of taxa with subchelate males, Heterotanais anomalus Sars is
      redescribed based on material from the Balearic Islands. The males of Konarus are
      now known to have a subchelate cheliped. The male (only) of Pseudoleptochelia
      bulbus from Melanesia is reassigned to Konarus cheiris, while Pseudoleptochelia
      bulbus sensu stricto is reassigned to Leptochelia together with its "minuta"-type
      male, as Leptochelia bulbus. Pseudoleptochelia straddi is rassigned to Konarus,
      together with its females from Queensland, Australia, which were previously
      assigned to Konarus cheiris. Pseudoleptocheliafairgo is confirmed as a member of
      Parakonarus, but material from Queensland is re-described as a new species. Other
      species previously assigned to Pseudoleptochelia are re-assessed: P. inermis, P.
      mercantilis and P. mortenseni sensu stricto are transferred to Leptochelia. The
      "small females" and males of P. mortenseni are transferred to Parakonarus as a
      new species. P. antarctica is provisionally reverted to Heterotanais, P.
      mergellinae to Leptochelia, and P. filum is tentatively transferred to
      Pseudonototanais. Pseudoleptochelia magna is synonymized with P. anomala.
      Pseudoleptochelia provincialis is tentatively transferred to Parakonarus.
      Pseudoleptochelia occiporta (females only) is reassigned to Leptochelia; the male
      of P. occiporta is considered to represent a species of Parakonarus.
      Pseudoleptocheliajuliae is reassigned to Parakonarus. Konarus, Makraleptochelia,
      Bassoleptochelia, Parakonarus and Pseudoleptochelia are placed in the new
      subfamily Konariinae. Generic relationships in this subfamily were confirmed by
      Principle Components Analysis. Catenarius is placed in the new subfamily
      Catenariinae.

PMID- 26312266
TI  - Two additional new species of Sphaerodactylus (Reptilia, Squamata, Gekkonoidea,
      Sphaerodactylidae) from the Honduran Bay Islands.
AB  - Recently, we described two new species of geckos of the genus Sphaerodactylus
      from the Bay Islands of Honduras. After further collections, and morphological
      and molecular analyses, we describe two additional species here. One of the new
      species belongs to the S. millepunctatus species group, which is centered in
      Middle America. The other new species belongs to the S. copei species group,
      which is centered in the Greater Antilles.

PMID- 26312267
TI  - A new species of Phyllodactylus (Reptilia, Squamata, Gekkonoidea,
      Phyllodactylidae) from Isla de Guanaja in the Honduran Bay Islands.
AB  - Morphological and molecular analyses of the Phyllodactylus populations on the
      Honduran Bay Islands of Guanaja, Roatan, and Utila demonstrate that the Guanaja
      population is best treated as a species distinct from the two other island
      populations. Thus, P. palmeus is restricted in distribution to Roatan and Utila
      islands and the Cayos Cochinos and a new species name is provided for the Guanaja
      Island population of the P palmeus species group.

PMID- 26312268
TI  - East African odontopygid millipedes 3: Two new genera; Lamelloramus and Aquattuor
      proposed to contain three new species (Diplopoda; Spirostreptida; Odontopygidae).
AB  - Two new genera and three new species in the millipede family Odontopygidae are
      described; Lamelloramus rhombi- formis, L. triangularis and Aquattuor
      denticulatus. All three species are found in the East Usambara Mountains.

PMID- 26312269
TI  - The Black Flies (Diptera: Simuliidae) of Iran.
AB  - Although Iran has a large geographic area encompassing 13 ecoregions, its
      simuliid fauna remains largely unexplored. To begin redressing this faunal gap,
      we reviewed literature records and coupled morphological and chromosomal
      identifications of material newly collected from 16 sites in Iran. Twenty-three
      nominal species are now recognized, including new country records for Simulium
      crassicaulum (Rubtsov) and Simulium alajense Rubtsov, and the southernmost world
      record for Simulium transcaspicum Enderlein. Multiple cytoforms of the Simulium
      aureum group, Simulium bezzii complex, and Simulium ornatum group were found.

PMID- 26312270
TI  - On the taxonomic validity of Pristimantis tepuiensis (Schluter & Rodder, 2007)
      and P. stegolepis (Schluter & Rodder, 2007), with remarks on the type series of
      P. guaiquinimensis (Schluter & Rodder, 2007).
AB  - The type series of Pristimantis guaiquinimensis (Schluter & Rodder, 2007), P.
      tepuiensis (Schluter & Rodder, 2007) and P. stegolepis (Schluter & Rodder, 2007)
      have been thoroughly examined. We highlight a number of discrepancies in the
      original descriptions that do not support the recognition of P. stegolepis and P.
      tepuiensis as valid species. We demonstrate that P. stegolepis should be
      considered ajunior synonym of P. vilarsi (Melin, 1941), and that P. tepuiensis
      should be considered a junior synonym of P. guaiquinimensis. We also point out
      that the sex of the holotype and paratype of P. guaiquinimensis have been wrongly
      determined.

PMID- 26312271
TI  - A new species of Centris (Xanthemisia) Moure, 1945 from South America with a
      synopsis of the known species of the subgenus in Colombia (Hymenoptera: Apidae:
      Centridini).
AB  - A synopsis of the species of Centris subgenus Xanthemisia Moure in Colombia is
      presented. The species identified are Centris ferruginea Lepeletier, C. lutea
      Friese and C. aureiventris, a new species from the Colombian Andes. Morphological
      characters of both sexes, distribution records and an identification key for the
      three species of the subgenus that occur in Colombia are provided.

PMID- 26312272
TI  - Vagabond but elusive: two newcomers to the Eastern Amazon (Araneae:
      Cithaeronidae; Prodidomidae).

PMID- 26312273
TI  - Synonymic notes on Palaearctic and Oriental Scydmaenus (Coleoptera:
      Staphylinidae: Scydmaeninae).

PMID- 26312274
TI  - The genus Buenoa Kirkaldy, 1904 (Hemiptera: Heteroptera: Nepomorpha:
      Notonectidae) in northern Brazil: inventory, new records, and new species.
AB  - The genus Buenoa contains 69 described species, 15 occurring in the North Region
      of Brazil. Here we present new records for the States of Para, Amazonas, Roraima,
      and Rond6nia. We examined 16 species: B. amnigenoidea Nieser, 1970, B.
      amnigenopsis Nieser, 1975, B. amnigenus White, 1879, B. exilidens Barbosa,
      Nessimian & Ferreira-Keppler, 2010, B. dilaticrus Barbosa, Nessimian & Ferreira
      Keppler, 2010, B. femoralis (Fieber, 1851), B. fuscipennis (Berg, 1879), B.
      incompta Truxal, 1953, B. konta Nieser & Pelli, 1994, B. macrotrichia Truxal,
      1953, B. platycnemis (Fieber, 1851), B. salutis Kirkaldy, 1904, B. tarsalis,
      Truxal, 1953, B. tibialis Truxal, 1957, B. truxali Nieser, 1968, and B. unguis
      Truxal, 1953; and a new species, B. deplanatylus Barbosa & Nessimian sp. nov. We
      found no material of four species with bibliographic records for the region: B.
      communis Truxal, 1953, B. pallens (Champion, 1901), B. pallipes (Fabricius,
      1803), and B. paranensis Jaczewski, 1928.

PMID- 26312275
TI  - Rediscovery and re-description of Ischnocnema nigriventris (Lutz, 1925) (Anura:
      Terrarana: Brachycephalidae).
AB  - Besides its brief original description in 1925 and information provided by one
      specimen collected in the 1980s, nothing else is known for Ischnocnema
      nigriventris (Lutz, 1925). Also, the poor preservation of the type series has
      hindered the association of this name with any known population of Ischnocnema.
      Fieldwork in Bertioga municipality, state of Sao Paulo, Brazil, revealed a
      population of Ischnocnema to which we were able to apply the name Ischnocnema
      nigriventris. We report this rediscovery, re-describe the species on the basis of
      the newly found specimens, and describe its mating call. Ischnocnema nigriventris
      is allocated to the Ischnocnema lactea species series and we propose a diagnosis
      based on a combination of morphological character states. The species is
      diagnosed by prominent conical tubercles on the upper eyelid, inguinal region and
      hidden areas of the hind limbs with yellow mottling in males and orange mottling
      in females, and by its advertisement call composed of two to four non-pulsed
      notes, the first one differentiated from the others by its lower intensity and
      different frequency. Ischnocnema nigriventris is only known from Parque das
      Neblinas (Bertioga municipality), Paranapiacaba (Santo Andre municipality), and
      Boraceia (Salesopolis municipality), localities in the state of Sao Paulo, Brazil

PMID- 26312276
TI  - A new species of the genus Achaemenothrombium (Acari: Achaemenothrombiidae) from
      Iran.
AB  - Achaemenothrombium dariusi Saboori, Wohltmann & Hakimitabar sp. nov. (Acari,
      Prostigmata: Trombidioidea) is described and illustrated from larvae
      ectoparasitic on Euxoafallax (Eversmann) (Lepidoptera: Noctuidae) from Sirch and
      Cheshmeh Bondar, Kerman province, Iran. It is the third species of this genus,
      which is recorded only from Iran. The status of this small family is discussed
      and a key to species of A chaemenothrombium (larvae) is presented.

PMID- 26312277
TI  - A new species of Satyrichthys (Teleostei: Peristediidae) from the Maldives
      Archipelago (Indian Ocean).
AB  - A new species of the genus Satyrichthys, Satyrichthys kikingeri sp. nov., is
      described from the Rasdhoo Atoll, Maldives Archipelago. The new species is placed
      in a group of Satyrichthys with at least three lip barbels and unequal parietal
      bones. It differs from its congeners in the combination of the following
      characters: (1) 3/3 lip and 1/0 chin barbels, (2) 15 fin rays in the second
      dorsal fin, 13 fin rays in the anal fin, (3) 25 bony plates in the dorsal, 29 in
      the upper lateral and 20 in the lower lateral rows, (4) 21st to 28th bony plates
      in the upper lateral row with forward directed spines and (5) parietal bones
      unequal in size on midline. Satyrichthys kikingeri sp. nov. is the first
      Satyrichthys species reported from the Republic of the Maldives.

PMID- 26312278
TI  - Ompok karunkodu, a new catfish (Teleostei: Siluridae) from southern India.
AB  - Ompok karunkodu, a new species of silurid catfish is described from the
      Amaravathi River, a right-hand tributary of the Kaveri [=Cauvery] River in Tamil
      Nadu, southern India. Ompok karunkodu can be distinguished from all congeners in
      the Indian subcontinent in having a markedly convex predorsal profile (vs. with a
      slight or distinct concavity in the supraethmoidal or supraoccipital region), and
      a unique combination of the following characters: prognathous lower jaw causing
      anterior profile of head to appear rounded when viewed laterally, maxillary
      barbel reaching to base of pectoral-fin spine, eye diameter 13.7% HL, head width
      13.0% SL, body depth at anus 14.2% SL, 65 anal-fin rays, caudal peduncle depth
      5.0% SL, caudal-fin length 12.6% SL, caudal fin with rounded lobes, 54 vertebrae,
      and dark midlateral stripe running along sides of body.

PMID- 26312279
TI  - Two new species of stoneflies (Plecoptera: Nemouridae) from Northeastern India
      with a checklist of the family in the Indian Subcontinent.
AB  - A new species of the genus Amphinemura (Plecoptera: Nemouridae: Amphinemurinae),
      A. baumanni sp. n. is described on the basis of five males collected in the
      Darjeeling District of West Bengal, India. A new species of the genus
      Sphaeronemoura (Amphinemurinae), S. siveci sp. n. is described on the basis of a
      single male collected in the West Garo Hills District of Meghalaya, India. A
      checklist of the family Nemouridae from the Indian Subcontinent is given with
      zoogeographical comments.

PMID- 26312280
TI  - A new species of Dialeurolobus (Hemiptera: Aleyrodidae) from Protea nitida in
      South Africa.
AB  - Dialeurolobus proteae sp. nov. is described from Protea nitida (Proteaceae) in
      South Africa, and from specimens intercepted on protea plants imported into the
      U.S.A. from South Africa. Its affinities to the other species of Dialeurolobus
      are discussed, and a diagnostic key is provided to identify the species of this
      genus.

PMID- 26312281
TI  - First species of the family Bogidiellidae Hertzog, 1936 (Crustacea: Amphipoda) in
      Chilean groundwaters: Patagongidiella wefkoi n. sp.
AB  - The first Chilean species of Bogidiellid amphipod, Patagongidiella wefkoi n. sp.,
      is described from freshwater springs in the Osorno Province, Los Lagos Region.
      The new taxon is characterized principally by the structure of the hypertrophied
      facial robust seta present on the peduncle of male uropod 1, and the modified
      dimorphic setae on the exopod of male pleopod 2. The new species is described and
      illustrated and its morphological relationships with the other species of this
      group are discussed.

PMID- 26312282
TI  - Second record of the West African hairy bush viper Atheris hirsuta Ernst & Rodel,
      2002 (Serpentes: Viperidae).

PMID- 26312283
TI  - A systematic review of the genus Constempellina Kieffer (Diptera: Chironomidae)
      from the Russian Far East, with description of a new species.
AB  - A new species of the genus Constempellina Brundin, 1947, C. tokunagai sp. n.,
      from the Russian Far East is described and figured as male, pupa and larva. The
      male and pupa of C. brevicosta (Edwards 1937) are redescribed and figured.
      Consequently, the generic diagnosis is emended. Keys to the males, pupae and
      larvae of Russian Constempellina are also given.

PMID- 26312284
TI  - Two new species and additional records of Lathrobium Gravenhorst (Coleoptera:
      Staphylinidae: Paederinae) from Guangxi, South China.
AB  - Material of the paederine genus Lathrobium Gravenhorst, 1802 from the Chinese
      province of Guangxi is examined. Five apterous species are identified, two of
      which are described as new to science: L. damingense Peng & Li sp. n. (Daming
      Shan) and L. hujiayaoi Peng & Li sp. n. (Maoer Shan). The female sexual
      characters of L. proprium Peng & Li are described and illustrated for the first
      time. With the newly described species in this paper, the Lathrobium fauna of
      Guangxi constitutes 9 species, that of the entire mainland China 168 species.

PMID- 26312285
TI  - Acrothoracican barnacles (Lithoglyptida) in Taiwan, including the taxonomic
      status of Balanodytes taiwanus Utinomi, 1950 and cryptic diversity of
      Auritoglyptes bicornis (Aurivillius, 1892).
AB  - We list five acrothoracican barnacles of the order Lithoglyptida currently found
      in Taiwanese waters, including two new records, Trypetesa habei Utinomi, 1962 and
      Berndtiapurpurea Utinomi, 1950 and a new undescribed species of the genus
      Lithoglyptes. We also investigate the morphology and molecular genetics of
      Balanodytes taiwanus Utinomi, from its type locality, Taiwan. The original
      description of B. taiwanus in Utinomi (1950a) reported the absence of caudal
      appendages. Re-examination of the somatic body of one of the syntype specimens
      (the other syntype only having an opercular bar remaining) of B. taiwanus
      deposited in the Seto Marine Laboratory in Japan, revealed the presence of caudal
      appendages. The morphology of our specimens collected in various locations in
      Taiwan fits the description in Utinomi (1950a) and all have caudal appendages.
      The diagnosis of Balanodytes Utinomi, 1950 is revised herein. The genus
      Armatoglyptes Kolbasov & Newman, 2005 is a nomen nudum and ajunior synonym of
      Balanodytes. Our results also show that the widespread species Lithoglyptes habei
      Tomlinson, 1963 is a junior synonym of B. taiwanensis. The molecular sequence
      divergencse of the 16S RNA and COI genes were studied for samples of another
      monotypic genus Auritoglyptes (A. bicornis) from different regions of Taiwan. It
      was shown that there are at least three phylogenetic clades in Taiwan, suggesting
      that Auritoglyptes represents a cryptic species complex.

PMID- 26312286
TI  - Nemaspela ladae sp. n., a new troglobitic nemastomatid (Opiliones, Dyspnoi,
      Nemastomatidae) from a Dinaric cave.
AB  - A new troglobitic Nemastomatidae from Mt. Romanija in Bosnia, is described and
      provisionally placed in the otherwise Caucasian genus Nemaspela Silhavy, 1966 for
      sharing morphological similarities. Nemaspela ladae sp. n. seems not closely
      related to the second troglobitic Balkan genus Hadzinia Silhavy, 1966, which
      shows closer relationship with Nemaspela femorecurvata Martens, 2006. New male
      specific characters shared by Hadzinia karamani (Hadzi, 1940) and several
      similar, still undescribed species, indicate Hadzinia as an independent lineage.
      The unusual distribution of the Hadzinia-Nemaspela complex might indicate its
      relictual status as elements of the paleo-European mainland fauna, which survived
      adverse climatic changes during the Pleistocene in southern refuges. Possible
      relation of this complex with the fossils Mitostoma gruberi Dunlop and Mitov,
      2009 from Bitterfeld and Baltic ambers is discussed. Further studies of the
      entire Hadzinia-Nemaspela complex and relatives are necessary to solve their
      phyletic and unusual zoogeographic connections.

PMID- 26312287
TI  - Annotated Checklist of the large branchiopod crustaceans of Idaho, Oregon and
      Washington, USA, with the "rediscovery" of a new species of Branchinecta
      (Anostraca: Branchinectidae).
AB  - We present a checklist of the large branchiopod crustaceans of Idaho, Oregon and
      Washington, USA. New distributional records are presented for most species,
      including the first records of Branchinecta constricta Rogers, 2006 and Lepidurus
      cryptus Rogers, 2001 from Idaho, the first record of B. oriena Belk & Rogers 2002
      from Oregon, the first record of B. mackini Dexter, 1956 and Artemiafranciscana
      Kellogg, 1906 co-occurring, and the first record of L. cryptus from Washington.
      Furthermore, we present the first record of Eulimnadia diversa Mattox, 1937 from
      west of the continental divide, which we interpret as an accidental introduction.
      In 1959, Lynch collected a new fairy shrimp species from Washington, deposited
      that material in the US National Museum, labeled "muddy fairy shrimp,
      Branchinecta lutulenta", but never described it. Numerous efforts have been made
      to rediscover extant populations since 1999. We rediscovered this species in
      2011, from two small pools from the vicinity of Lynch's original collection site,
      which appears to have been destroyed. Branchinecta lutulenta sp. nov. is most
      closely related to B. lindahli Packard, 1883 and B. oterosanvicentei Obregon
      Barboza et al., 2002. Branchinecta lutulenta sp. nov. is readily separable from
      all other Branchinecta species by the form of the male second antennal distal
      antennomere and the ornamentation of the female dorsum.

PMID- 26312288
TI  - Erythrocyte nuclear size as a better diagnostic character than cell size in the
      identification of live cryptic polyploid species.
AB  - It is well documented in anurans the cryptic condition of many species complexes
      involving polyploids. In these complexes the character that clearly
      differentiates them is the number of chromosome complements. The blood cells of
      amphibians conserve their nucleus, and so the erythrocyte size is correlated with
      the DNA content. We analyzed two cryptic-polyploid complexes occurring in the
      center of Argentina: Odontophrynus cordobae (2n)/O. americanus (4n) and
      Pleurodema kriegi (4n)/P. cordobae (8n). Our aim was evaluate the efficiency in
      the utilization of nuclear area with respect to cellular area of the erythrocytes
      to define the limits values for the identification of cryptic-polyploid species.
      We studied 110 individuals of Pleurodema and 116 individuals of Odontoprhynus.
      For each individual, we measured the cellular and nuclear length (L) and width
      (A) of 40 erythrocytes (Area = L*A*pi/4) and boundary values were calculated
      using distribution curves. In both complexes studied, the erythrometric
      parameters showed significant differences between related species. Moreover, in
      both complexes the nuclear area was more efficient for identifying the species
      (Pleurodema: 34.39 um2 (probability = 99.96%) and Odontophrynus: 24.02 um2
      (99.075%)) than the cell area (Pleurodema: 273.08 um2 (97.55%) y Odontophrynus:
      197.69 um2 (97.94%)). Greater efficiency found using nuclear area is novel and
      significant because most studies use only the cell area to differentiate
      polyploid complexes.

PMID- 26312289
TI  - The Campsicnemus popeye species group (Diptera: Dolichopodidae) from French
      Polynesia.
AB  - A new species-group (the popeye group) of the mega-diverse dolichopodid genus
      Campsicnemus from French Polynesia is described to include six new species: C.
      craigi Evenhuis, sp. nov.; C. elinae Evenhuis, sp. nov.; C. meyeri Evenhuis, sp.
      nov.; C. moorea Evenhuis, sp. nov.; C. pectinatus Evenhuis, sp. nov.; and C.
      popeye Evenhuis, sp. nov. Keys to Campsicnemus species groups in French Polynesia
      and to species in the C. popeye group are given.

PMID- 26312290
TI  - Simulium (Nevermannia) khunklangense, a new species of black fly (Diptera:
      Simuliidae) from Chiang Mai, Thailand.
AB  - Simulium (Nevermannia) khunklangense sp. nov. is described from females, males,
      pupae and larvae collected in Doi Inthanon National Park, Chiang Mai, Thailand.
      This new species is placed in the vernum species-group of the subgenus
      Nevermannia and is similar to S. (N.) chomthongense Takaoka & Srisuka described
      from Doi Inthanon National Park, Thailand, but is distinguished in the male by
      the number of enlarged upper-eye facets and the relative width of the hind
      basitarsus against the hind tibia and femur, and in the pupa by the short common
      basal stalk of the gill and the cocoon with an anterodorsal bulge or a short
      anterodorsal projection. Taxonomic notes are provided to separate this new
      species from five other known species of the vernum species-group, which share an
      accessory sclerite on the larval abdomen, a rare characteristics in this species
      group.

PMID- 26312291
TI  - A new species of Notosacantha Chevrolat (Coleoptera: Chrysomelidae: Cassidinae:
      Notosacanthini) from southern India.
AB  - Notosacantha bertounesquei sp. nov. is described from Kerala state in southern
      India. This new species belongs to the group of two large species hitherto known
      only from Sri Lanka. Checklist and key to Notosacantha species of Sri Lanka and
      southern India are provided.

PMID- 26312292
TI  - Two new species of the genus Xizicus, 1993 (Orthoptera: Tettigoniidae:
      Meconematinae) from Xizang, China.
AB  - In this paper two new species of the genus Xizicus from Xizang, China are
      described, Xizicus (Axizicus) spinocercus Jiao & Shi sp. nov. and Xizicus
      (Axizicus) xizangensis Jiao & Shi sp. nov. The type specimens are deposited in
      the Museum of Hebei University.

PMID- 26312293
TI  - On some taxonomically confused species of the genus Amphiesma Dumeril, Bibron &
      Dumeril, 1854 related to Amphiesma khasiense (Boulenger, 1890) (Squamata,
      Natricidae).
AB  - Three species of the genus Amphiesma Dumeril, Bibron & Dumeril, 1854 have long
      been confused in the literature, with each other and with other species of the
      genus. Amphiesma khasiense (Boulenger, 1890) has been considered to inhabit a
      large geographical region, extending from north-eastern India, east to Vietnam
      and southern Thailand. Amphiesma boulengeri (Gressitt, 1937) has been regarded as
      a species endemic to south-eastern China. Amphiesma inas (Laidlaw, 1901) has been
      recorded from West Malaysia, Thailand and Indonesia (Sumatra). A multivariate
      analysis of morphometric and meristic characters shows that these three species
      can be separated by combinations of characters in the scalation and pattern, the
      most obvious being the structure of the postocular streak. On the basis of our
      analysis and after comparison with name-bearing type specimens, Amphiesma
      khasiense is restricted to north-eastern India, Myanmar, western Yunnan Province
      of China, northern Laos and northern and western Thailand. Other populations from
      south-eastern China, Vietnam, other parts of Laos, Cambodia and central Thailand,
      which have been recorded in the literature as A. khasiense, A.johannis or
      Amphiesma modestum (Gunther, 1875), should be referred to Amphiesma boulengeri.
      Amphiesma inas (Laidlaw, 1901) is a valid species endemic to mountain ranges of
      southern Peninsular Thailand and West Malaysia. The mention of Amphiesma inas in
      Sumatra is erroneous, being based on the second known specimen of Amphiesma
      kerinciense David & Das, 2003, which is here redescribed. A key to species of the
      Amphiesma khasiense group and other species sharing a greyish-brown background
      without conspicuous dark and pale stripes, is provided.

PMID- 26312294
TI  - Description of two new species of the genus Tmesiphodimerus gen. n. (Coleoptera:
      Staphylinidae: Pselaphinae) from South Asia.
AB  - Tmesiphodimerus Coulon and Yin, new genus (Pselaphitae: Tmesiphorini) is proposed
      for T. sinensis Yin and Coulon, new species from Hainan, South China (type
      species), and T. malaysianus Coulon and Yin, new species from Perak, West
      Malaysia. The new taxa are described, with their major diagnostic features
      illustrated. The taxonomic placement of Tmesiphodimerus is discussed.

PMID- 26312295
TI  - A new species of the sponge-associated pontoniine shrimp genus Nippontonia Bruce
      & Bauer, 1997 (Decapoda, Caridea, Palaemonidae) from Sabah, Malaysia.
AB  - A sponge-associated species of the genus Nippontonia new to science is described
      from Semporna, Sabah, Malaysia. The only other species in the genus is also known
      to be a sponge-dweller. The new species can be distinguished from its con- gener
      by a suite of characters mainly of the anterior appendages.

PMID- 26312296
TI  - Chromosomes and their meiotic behavior in twelve species of the subfamily
      Harpactorinae (Hemiptera: Heteroptera: Reduviidae) from north India.
AB  - The chromosome complements and male meiosis of 12 species belonging to the
      subfamily Harpactorinae from north India have been described for the first time.
      All the species show twelve pairs of autosomes and X multiplicity with 9 species
      having X1X2X3Y and 3 species having X1X2Y sex mechanism. The general course of
      meiosis in all the presently studied species is fairly uniform. Autosomes show a
      high degree of decondensation and sex chromosomes are condensed during the
      diffuse stage. Single terminal chiasma per bivalent is seen in all except Sycanus
      croceovittatus Dohrn, which has two terminal chiasmata in one or two bivalents. A
      regular arrangement of chromosomes at metaphase I has been observed in 7 species,
      but in the rest, no definite pattern is recorded. In Euagoras erythrocephala
      Livingstone and Ravichandran, more than one type of arrangement is seen. At
      metaphase II, autosomes form a ring in the center of which lies the
      pseudomultivalent in all the species excepting Rhynocoris costalis (Stal). In
      Sycanus croceovittatus, a proper pseudotetravalent is lacking. Cytogenetic trends
      within the subfamily have been discussed in the light of newly added cytogenetic
      data of 12 species, which may later be used in tracing the evolution of
      chromosomes in Harpactorinae.

PMID- 26312297
TI  - The ANDEEP Tanaidacea (Crustacea: Peracarida) revisited II: the family
      Anarthruridae and family incertae sedis, with descriptions of three new species
      and the erection of a new genus.
AB  - Specimens collected during the ANDEEP I and II expeditions revealed three new
      species belonging to the family Anarthruridae and family incertae sedis. One new
      species of Anarthruridae, Ithyomus antarcticus n. sp. is described. Also
      described are two new species belonging to genera currently not assigned to a
      family; one in the genus Parafilitanais (P. denticulus n. sp.) and one in
      Pseudoarthrura (P. tuberculata n. sp.). The genus Cristatotanais is removed from
      Anarthruridae, while P. setoserrata is removed from Pseudoarthrura and elevated
      to genus rank under the name Selvagentanais gen. nov.

PMID- 26312298
TI  - A new species of Psilorhynchus (Teleostei: Psilorhynchidae) from the Chindwin
      basin of Manipur, India.
AB  - Psilorhynchus chakpiensis, new species, is described from the Chakpi River,
      Chindwin basin in Manipur, India. It is distinguished from its congeners by a
      combination of characters: a dome-shaped rostral cap with horizontally arranged
      pointed tubercles, 1-2 rows of prominent globular papillae behind the upper lip,
      three unbranched and nine branched dorsal-fin rays, 30-31 lateral-line scales,
      head width 74-83% HL, and characteristic colour bands on the dorsal and caudal
      fins. It is distinguished from all congeners in having a caudal-fin pattern
      consisting of two black bars, one incomplete bar near the base of the upper lobe,
      and a complete bar across the centre of the fin, traversing from the upper to the
      lower margin of the fin.

PMID- 26312299
TI  - New species and records of Anacroneuria (Plecoptera: Perlidae) from Rio de
      Janeiro State, Brazil.
AB  - Six species of Anacroneuria are recorded from Parque Nacional do Itatiaia and
      Bacia do Rio Macae, Rio de Janeiro State, Brazil including the description of a
      new species, A. itatiaiensis. Anacroneuria debilis (Pictet) is redescribed from
      newly collected specimens. Comments on other Anacroneuria species from Rio de
      Janeiro State, Brazil are also presented.

PMID- 26312300
TI  - Tropical insect collections and DNA extraction, using Rhodnius Stal 1859
      (Hemiptera: Heteroptera: Reduviidae: Triatominae).

PMID- 26312301
TI  - Discovery of Recent thecideide brachiopods (Order: Thecideida, Family:
      Thecideidae) in Sulawesi, Indonesian Archipelago, with implications for
      reproduction and shell size in the genus Ospreyella.
AB  - For the first time thecideide brachiopods have been discovered in the Indonesian
      Archipelago. All specimens were collected in a water depth of 30 m from an old
      shipwreck, the "Mutiara", which represents a remarkable habitat for these cryptic
      brachiopods despite its artificial nature. The thecidellinine species Minutella
      cf. minuta and the lacazelline species Ospreyella mutiara n. sp. are described
      and illustrated comprehensively, including their shell ontogeny. The inclusion of
      the new species O. mutiara in the genus Ospreyella Luter and Worheide, 2003 is
      based on results of an integrated approach combining morphological, ontogenetic
      and genetic studies. Relevant morphological characters diagnostic for Ospreyella
      are established. In addition, all Recent lacazelline brachiopod genera are
      confirmed as valid taxa using molecular methods. The small body size of 0.
      mutiara and the weakly developed brachidium in comparison to other Ospreyella
      species as a consequence of heterochrony is discussed in more detail. O. mutiara
      is the first species of the exclusively gonochoristic genus Ospreyella for which
      hermaphroditism is now documented.

PMID- 26312302
TI  - A new species of callianassid ghost shrimp of the genus Nihonotrypaea Manning &
      Tamaki, 1998 (Crustacea, Decapoda, Axiidea, Callianassidae) from southern part of
      the Russian coast of the Sea of Japan.
AB  - A new species of callianassid shrimp genus Nihonotrypaea Manning & Tamaki, 1998
      (Crustacea: Decapoda: Axiidea: Callianassidae) is described from the Peter the
      Great Bay, Primorye, Russian coast of the Sea of Japan. The species clearly
      differs from other representatives of the genus by unique armature of ventral
      margin of merus and different form of carpus of major cheliped in males and
      yellow-greenish coloration never observed in other species of the genus
      Nihonotrypaea.

PMID- 26312303
TI  - New species of Pseudosmittia Edwards, 1932 and new records of Allocladius
      Kieffer, 1913 (Diptera: Chironomidae, Orthocladiinae) from South America.
AB  - Three new species of Pseudosmittia Edwards from the Neotropical region, P.
      satheri, P. larga and P. trapezoidea, are described and figured as males.
      Allocladiusfortispinatus (Edwards), A. globosus Andersen et al. and A. quadrus
      Andersen et al. are redescribed on the basis of new material and their
      geographical distribution updated. A phylogenetic analysis was performed in order
      to assess the phylogenetic relationships of the new species. As a result, the
      species P. soetheri and P. larga are found to be sister species belonging to the
      angusta group. The species P. trapezoidea is the sister group of the clade ((P.
      propetropis (P. tropis--P. lamellata)) and belongs to the brevifurcata group
      sensu lato.

PMID- 26312304
TI  - The larvae of Altica koreana (Ogloblin) and A. viridicyanea (Baly) (Coleoptera:
      Chrysomelidae: Galerucinae: Alticini).
AB  - The first instar and mature larvae of Altica koreana (Ogloblin) and A.
      viridicyanea (Baly) are described and illustrated for the first time and compared
      with larvae of Altica caerulescens (Baly), A. cirsicola Ohno, and A. fragariae
      (Nakane). A key to the five related Altica species is also given.

PMID- 26312305
TI  - To the knowledge of cuckoo wasps (Hymenoptera: Chrysididae) of the Balearic
      Archipelago, Spain.
AB  - The Chrysididae of the Balearic Archipelago were studied by operating four
      Malaise traps in the Mallorca and Menorca Islands. Traps captured 98 individuals
      belonging to 19 species. Including all available data from literature, the number
      of species in this archipelago rise to 34. Hedychridium balearicum Strumia, sp.
      nov (Mallorca) is described and key to the Hedychridium monochroum species-group
      is given. Extrapolation from available data suggests the presence of about 58 to
      107 Chrysididae species in the Balearic Archipelago.

PMID- 26312306
TI  - Remarkable range extension of the previously monotypic braconid genus Wushenia
      Zettel (Hymenoptera: Braconidae: Cheloninae), with description of a second
      species from Australia.
AB  - The apparently rare chelonine wasp genus Wushenia Zettel was previously known
      only from a single species Wushenia nana Zettel, collected by Townes at 1150 m
      from Wushe, Taiwan in 1983. Here we describe a second species, Wushenia
      australiensis sp. nov. from coastal New South Wales, Australia. This second
      species extends the known distribution of the genus from the Oriental into the
      Australasian region, indicating either an extreme disjunct distribution or that
      Wushenia may also occur on the landmasses inbetween, e.g. the Philippines,
      Malaysia, Indonesia and/or Papua New Guinea. In addition to a detailed
      description of the new species, a re-diagnosis of the genus and type species, and
      a key to species are presented.

PMID- 26312307
TI  - A new species of Poliaspoides MacGillivray (Hemiptera, Diaspididae) on Bambusa
      siamensis (Poaceae) imported into Turkey.
AB  - The adult female and first-instar nymph of a new species of armoured scale
      insect, Poliaspoides bambusae sp.n. (Diaspididae), is described and illustrated.
      The new species was collected in Turkey on imported ornamental Bambusa siamensis
      (Poaceae) from an unknown source.

PMID- 26312308
TI  - A new species of lizard in the genus Caledoniscincus (Reptilia: Scincidae) from
      southern New Caledonia and a review of Caledoniscincus atropunctatus (Roux).
AB  - A new species of skink, Caledoniscincus notialis sp. nov., is described from the
      ultramafic ranges in southern New Caledonia. It is most similar to, and has
      previously been referred to Caledoniscincus atropunctatus (Roux), a species with
      a widespread distribution throughout the Grand Terre and Loyalty Islands. The new
      species is distinct genetically from all other Caledoniscincus and can be
      distinguished by a unique pattern of dorsal coloration in males. Its range
      extends over much of the extensive ultramafic block in the south of the island,
      including the Goro Plateau and the mountain ranges at the southern edge of the
      Chaine Centrale north to Mt. Humboldt. It occurs mainly in humid forest habitat,
      much of which is now present only as isolated fragments in southern New
      Caledonia. Its preference for a habitat that has undergone a significant
      reduction in area of extent in a region under pressure from a range of
      anthropogenic threats suggests this new species is of conservation concern, and
      could be ranked as Vulnerable under IUCN listing. The genetic relationships of a
      redefined Caledoniscincus atropunctatus identifies two major subgroups, one
      located mainly in the northern and central-east regions of Grand Terre and the
      other in the southern and central-west regions and also including the population
      on the Loyalty Islands.

PMID- 26312309
TI  - A new species of Elachistocleis (Anura: Microhylidae) from north-western
      Argentina.
AB  - Elachistocleis haroi sp. nov. is described from El Algarrobal, Jujuy province,
      north-western Argentina. The new species is diagnosed by the dorsal pattern of
      mid-longitudinal bright yellow stripe from the intraocular zone, surpassing the
      post-cephalic transverse skin fold, to vent; dorsum grayish brown mottled with a
      paravertebral symmetric pattern of dark spots resembling a pine tree; and a thin
      regular yellow line on the posterior surface of the thighs and tibiae. The
      advertisement call is a long trill with an average duration of 3.18 seconds,
      multipulsed with a mean dominant frequency of 4.56 kHz. The tadpole is
      characterized by the oral dermal flaps with papillae-like edges.

PMID- 26312310
TI  - Six new Dinotrema species (Hymenoptera, Braconidae) from Spain, with prescutellar
      pit and medially sculptured propodeum.
AB  - Descriptions of six new species of the genus Dinotrema from Spain with smooth or
      only medially sculptured propodeum are provided. The new species described are:
      D. achterbergi sp. nov., D. broadi sp. nov., D. enanum sp. nov., D. fischerianum
      sp. nov., D. munki sp. nov. and D. pappi sp. nov.

PMID- 26312311
TI  - A new genus and species of Planopinae (Xenarthra: Tardigrada) from the Miocene of
      Santa Cruz Province, Argentina.
AB  - Prepoplanops boleadorensis, a new genus and species of Planopinae (Xenarthra,
      Tardigrada), is described herein. The new taxon is based on a nearly complete
      specimen recovered from the Cerro Boleadoras Formation (Miocene, Rio Zeballos
      Group), in northwestern Santa Cruz Province, Argentina. The shape and length of
      the predentary region of the skull and the length of the diastema of Prepoplanops
      boleadorensis differ from those present in the species of Planops. The
      posterolateral opening of the mandibular canal and the position of the posterior
      margin of the mandibular symphysis differ from those of species of Prepotherium.
      In addition, Prepoplanops boleadorensis differs from Planops martini in the size
      of the humeral tuberosities, the development of the deltoid crest, the position
      of the distal margin of the humeral trochlea, the shape and position of the
      olecranon, the development of the femoral epicondyles, and the shape of the
      medial margins of the patellar trochlea and medial condyle. On the other hand, it
      differs from Prepotherium potens in the shape of the medial margin of the medial
      condyle. The recognition of Prepoplanops boleadorensis increases the diversity of
      Planopinae for the Miocene of Patagonia, Argentina.

PMID- 26312312
TI  - The larva of Psilopteryxpsorosa (Kolenati 1860) (Trichoptera: Limnephilidae) with
      notes on ecology and zoogeography.
AB  - The paper gives a description of the hitherto unknown larva of Psilopteryx
      psorosa (Kolenati 1860), subspecies bohemosaxonica Mey & Botosaneanu 1985
      (Trichoptera: Limnephilidae: Limnephilini, Chaetopterygina; Vshivkova et al.
      2007). Information on the morphology of the larva is given and the most important
      diagnostic features are illustrated. In the context of already available keys,
      the larva of P psorosa bohemosaxonica keys together with Pseudopsilopteryx
      zimmeri (McLachlan 1876), Chaetopteryxfusca Brauer 1857 and C. villosa (Fabricius
      1798). Psilopteryxpsorosa is not yet separable from P zimmeri but may be easily
      separated from the two Chaetopteryx species by the median fusion of setal groups
      sal at the first abdominal sternum in P psorosa which is lacking in C. fusca and
      C. villosa. With respect to distribution, P. psorosa bohemosaxonica is present in
      the Bohemian Forest and the Erzgebirge (Upper Austria, Czech Republic, and
      Germany). In addition, ecological characteristics are briefly discussed.

PMID- 26312313
TI  - Aradidae from Vietnam I. Two new genera of micropterous Mezirinae (Hemiptera:
      Heteroptera: Aradidae).
AB  - Two new micropterous genera and three species of micropterous Mezirinae are
      described and illustrated. Although of similar habitual appearance as the
      Oriental genus Hutanicoris Heiss 1993, the two new genera are distinguished at
      once by the unique structures of their metathoracic evaporatoria.

PMID- 26312314
TI  - Neotype designation for Sinonamuropteris ningxiaensis Peng, Hong et Zhang, 2005
      (Grylloblattida: Sinonamuropteridae).

PMID- 26312315
TI  - Complete nucleotide sequence and organization of the mitochondrial genome of
      Sirtheneaflavipes (Hemiptera: Reduviidae: Peiratinae) and comparison with other
      assassin bugs.
AB  - The complete sequence of the mitochondrial (mt) genome of the assassin bug,
      Sirtheneaflavipes (Stal), was determined. The circular genome is 15, 961 bp long
      and contains a standard gene complement, i.e., the large and small ribosomal RNA
      (rRNA) subunits, 22 transfer RNA (tRNA) genes, 13 protein-coding genes (PCGs),
      and the 1, 295 bp control region. The nucleotide composition of S. flavipes mt
      genome is 71.8% AT-rich, reflected in the predominance of AT-rich codons in PCGs.
      Compared with the other three reduviid species available in complete mt genomes,
      the genome architecture as well as the nucleotide composition, codon usage, and
      amino acid composition reflected high similarity. All PCGs use standard
      initiation codons (ATN); however, ND4L and ND1 started with GTG. Canonical TAA
      and TAG termination codons are found in nine PCGs, the remaining four (COIII,
      ND3, ND5, and ND]) have incomplete termination codons. All tRNAs have the typical
      clover-leaf structure, except the dihydrouridine (DHU) arm of tRNASer(AGN) forms
      a simple loop as seen in many other metazoans. Secondary structure models of the
      ribosomal RNA genes of S. flavipes are presented and are similar to those
      proposed for other insects. The structure of rrnL is more conservative than that
      of rrnS among sequenced assassin bugs. The monophyly of Reduviidae is highly
      supported by Bayesian inferences, and the Peiratinae presents a sister position
      to the Triatominae+ (Salyavatinae + Harpactorinae).

PMID- 26312316
TI  - Grandaustralis, a new genus and Grandaustralis boomerang, a new species of
      Cetoniinae (Coleoptera: Scarabaeidae) from Western Australia.
AB  - Grandaustralis new genus and Grandaustralis boomerang new species are described
      from Western Australia. Grandaustralis is placed in the tribe Schizorhinini
      (Coleoptera: Scarabaeidae: Cetoniinae).

PMID- 26312317
TI  - Taxonomy of the genus Kochogaster Kaminski et Ras, 2011 (Coleoptera:
      Tenebrionidae: Pedinini), with description of a second known species.
AB  - A second species of the genus Kochogaster Kaminski et Ras (K. gerardi sp. n.) is
      described from the surroundings of Garissa (Kenya). The taxonomic concept and
      phylogenetic relationships of Kochogaster are discussed. A distributional map is
      presented with complete faunistic data on the genus. Additionally, the original
      spelling of the name Anchophthalmus inuelleri Schimrosczyk, 2010 is emended to A.
      muellerae due the rules of the International Code of Zoological Nomenclature.

PMID- 26312318
TI  - Three new species of the genus Issikiopteryx Moriuti, 1973 (Lepidoptera:
      Lecithoceridae: Lecithocerinae) from China.
AB  - The genus Issikiopteryx Moriuti is further studied in China based on the
      specimens collected from Zhejiang, Guizhou and Tibet. Three new species are
      described: I. parelongata sp. nov., I. suiyangensis sp. nov. and I. nigeriflava
      sp. nov. Photographs of adults and genital structures are provided.

PMID- 26312319
TI  - Revision of the Rhyacophila stigmatica Species Group in Turkey with descriptions
      of three new species (Trichoptera, Rhyacophilidae).
AB  - The Rhyacophila stigmatica Species Group in Turkey is revised and three new
      species (Rhyacophila alaplica sp. n. from northwestern Turkey, and Rhyacophila
      caniliensis sp. n., and R. torulensis sp. n., both from northeastern Turkey) are
      described and illustrated. A redescription of R. zwickorum Malicky 1972 is given.
      A key to the Turkish males and females of the Group is provided.

PMID- 26312320
TI  - Two new species of Phyllocladus (Coleoptera: Pyrochroidae: Pyrochroinae) from
      China, with a key to males of the Chinese species.
AB  - Phyllocladus bilobatus, sp. nov., is described from three males taken in
      mountainous regions of western Hubei and northern Sichuan provinces in central
      China. All specimens were collected in mid-June at elevations ranging from 1950
      2000 meters. Phyllocladus cinnabarus, sp. nov., is described from a single male
      collected in Jiangkou County, northeastern Guizhou province, south-central China.
      An illustrated key to males of the four Chinese Phyllocladus is presented.

PMID- 26312321
TI  - Early development of fat snook, Centropomus parallelus (Poey 1860) (Teleostei,
      Centropomidae) from Southeastern Brazil.
AB  - Early development of fat snook, Centropomus parallelus (Poey 1860), is described
      based on embryos. and larvae obtained from rearing experiments and from specimens
      caught in the field, in Cananeia, southeastern Brazil, during December 1999
      January 2000. Larvae of common snook, C. undecimalis, were also collected to
      compare the pigmentation pattern and body shape. Eggs of C. parallelus were
      relatively small (0.65 to 0.70 mm in diameter), spherical, and usually with a
      single oil globule. Notochord length (NL) of newly hatched ranged between 1.1 mm
      to 1.4 mm. Notochord flexion began at 3.4 mm NL and was usually completed by 4.0
      mm SL. Larval and early juvenile of both species were very similar with tenuous
      distinction, however, some morphological and pigmentation characters were used to
      distinguish their early stages. The main differences were as follow: trend of
      lower values of the ratio of body depth to body length (BD/BL) for C. parallelus
      larger than 10.0 mm SL; absence of the post-temporal spine in C. undecimalis;
      absence of pigmentation along the dorsal midline of C. parallelus larvae by 2.6
      7.0 mm; and presence of a pair of dendritic melanophores posterior to the bases
      of pelvic fins in C. parallelus larger than 6.0.

PMID- 26312322
TI  - Adinopsis nippon, a new species of marsh-dwelling rove beetle (Coleoptera:
      Staphylinidae: Aleocharinae: Deinopsini) from Japan, with an annotated catalogue
      of Adinopsis species of the world.
AB  - Adinopsis nippon sp. n. is described from Japan and represents the first
      discovery of the genus Adinopsis in the temperate zone of the East Palearctic
      region. It is closely related to A. myllaenoides (Kraatz) known from North and
      South America and is placed in the myllaenoides species group. An annotated
      catalogue of the world species of Adinopsis is presented.

PMID- 26312323
TI  - The first troglobitic Pseudonannolene from Brazilian iron ore caves
      (Spirostreptida: Pseudonannolenidae).
AB  - Pseudonannolene spelaea n. sp. is the first strictly cave-dwelling species
      described for the family Pseudonannolenidae. It is found in iron ore caves in the
      Brazilian Amazon. The family Pseudonannolenidae is exclusively Neotropical and
      frequently found in caves of Brazil, from which 20 species are known. The new
      species is compared with its congeners and with related cave-dwelling species.
      The family Pseudonannolenidae is discussed, and comments are presented on the
      conservation status of the caves where the species is found, which potentially
      may be the target of anthropogenic impacts resulting from iron ore extraction.

PMID- 26312324
TI  - Occurrence of Xyleborus bispinatus (Coleoptera: Curculionidae: Scolytinae)
      Eichhoff in southern Florida.
AB  - Xyleborus bispinatus Eichhoff is reported from Florida for the first time. It was
      previously unrecognized and not distinguished from Xyleborusferrugineus (F.).
      There is no reason to believe at this point that it represents an introduction.
      Rather it is one of a group of widely distributed Neotropical species that are
      also found in southern Florida. Characters are discussed to allow it to be
      distinguished from X. ferrugineus and X. impressus Eichhoff.

PMID- 26312325
TI  - Taxonomic adjustments in the systematics of the southern African lacertid lizards
      (Sauria: Lacertidae).
AB  - Molecular phylogenetic analyses of southern African lacertid lizards (Eremiadini)
      using mitochondrial and nuclear markers revealed two examples of generic
      assignments incompatible with monophyletic clades. Australolacerta Arnold 1989, a
      genus endemic to South Africa and to which two isolated species have been
      referred, is paraphyletic at the generic level. In addition, the species
      Ichnotropis squamulosa Peters 1854 was found to be embedded within the genus
      Meroles. To resolve the paraphyly in Australolacerta we erect a new genus,
      Vhembelacerta Edwards, Branch, Herrel, Vanhooydonck, Measey, & Tolley, gen. nov.,
      to accommodate Lacerta rupicola FitzSimons 1933. To maintain a monophyletic
      Ichnotropis Peters 1854, Ichnotropis squamulosa Peters 1854 is transferred to
      Meroles Gray 1838, now named Meroles squamulosus comb. nov. Where necessary the
      genera affected by these actions are re-characterized.

PMID- 26312326
TI  - Six new species of Cernotina Ross, 1938 (Trichoptera: Polycentropodidae) from
      Brazil.
AB  - Six new species of Cernotina Ross are described from two Brazilian states:
      Cernotina anhanguera sp. nov., Cernotina bispicata sp. nov., and Cernotina
      falcata sp. nov. from Goias State (Cerrado biome) and Cernotina lanceolata sp.
      nov., Cernotina longispina sp. nov., and Cernotina sinuosa sp. nov. from Espirito
      Santo State (Atlantic Forest biome). In addition, we report the first record of
      Cernotina spinigera Flint 1971 from Goias State.

PMID- 26312327
TI  - A review of the genus Compterosmittia Saether, 1981 (Diptera: Chironomidae) from
      China.
AB  - The genus Compterosmittia Saether, 1981 from China is reviewed. Three new
      species, C. duodecima sp. n., C. lii sp. n. and C. procera sp. n. are described
      as adult males. C. nerius (Curran, 1930), C. oyabelurida (Sasa, Kawai et Ueno,
      1988) and C. togalimea (Sasa et Okazawa, 1992) are recorded from China for the
      first time and annotated; as a result the diagnosis for the genus is emended. A
      key to adult males of all known Compterosmittia is also presented.

PMID- 26312328
TI  - A new species and new records of Pachytullbergiidae and Tullbergiidae
      (Collembola: Onychiuroidea) from littoral of China, with notes on the variations
      of postantennal organ.
AB  - Sensiphorura oligoseta sp. nov. is described from the sand beach of Pacific coast
      of China. It is the second member of the genus and differs from S. marshalli
      Rusek, 1976 by the smaller apical vesicle on antennae, and fewer setae on
      abdominal tergites. Psanunophorura neocaledonica Thibaud & Weiner, 1997 and
      Mesaphorura yosii (Rusek, 1967) are also found to be widely distributed on the
      coast. Chinese specimens of P. neocaledonica are described, notes to variations
      of its postantennal organ are given.

PMID- 26312329
TI  - A new species of Furciseta (Diptera, Ctenostylidae) from the Brazilian Amazon.
AB  - Furciseta Aczel, 1956 [type species: F. plaumanni (Hennig, 1952)] was described
      as a monotypic genus from southern Brazil and is known only from the type
      material. Herein, F hyalipennis n. sp. is described and illustrated based on
      three males and one female collected in the Brazilian states of Amazonas and
      Maranhao. An illustrated key to the two known species is presented.

PMID- 26312330
TI  - Thraulodes bonito sp. nov. (Ephemeroptera: Leptophlebiidae) from Rio de Janeiro
      State, Southeastern Brazil.
AB  - A new species of Thraulodes Ulmer, 1920 is described from Rio de Janeiro. The
      species resembles the recently published Thraulodespelicanus Mariano and
      Froehlich, 2011 (in Mariano et al. 2011) due to the length and width of the
      penes. However, Thraulodes bonito sp. nov. differs from this and all other
      species of the genus by the wide penes, the triangular shape of the styliger
      plate with median projection short and apex rounded, the abdominal color pattern
      and the presence of 1-3 weakly marked cross veins basal to bullae. The new
      species is described based on male imagos, female subimagos and nymphs.

PMID- 26312331
TI  - First record of Beaded Lacewings (Neuroptera, Berothidae) from Colombia.
AB  - The family Berothidae is recorded for the first time in Colombia, with
      Spiroberotha sanctarosae Adams, 1989, collected from Tayrona National Park and
      Zambrano municipality, in Magdalena and Bolivar departments, respectively. The
      external morphology and male genitalia are illustrated, providing complementary
      information to the original description. A key to separate species of
      Spiroberotha, as well as a list of species of Central- and South American
      Berothidae are presented.

PMID- 26312333
TI  - Guerothrips moundi, gen. et sp.n. (Thysanoptera, Thripidae) from Chiapas, Mexico.
AB  - Guerothrips moundi gen. et sp. n., (Thripidae, Thripinae) is described from
      flowers of the herbaceus plant Waltheria indica (Sterculiaceae) found in
      Tapachula, Chiapas, Mexico. G. moundi is a member of the Frankliniella genus
      group, but is distinguished by the presence of sternal discal setae on the
      abdomen. The available specimens are all brachypterous.

PMID- 26312332
TI  - Two new species of Sericosura Fry & Hedgpeth, 1969 (Arthropoda: Pycnogonida:
      Ammotheidae) from a hydrothermal vent on the East Pacific Rise.
AB  - Between 17th October and 9th November 2009, the third leg of the Chinese DY115-21
      cruise on board the R/V Dayangyihao, confirmed two new hydrothermal fields near
      the equatorial East Pacific Rise. Five pycnogonid specimens were obtained by deep
      sea TV-grab from one of the new hydrothermal vents named 'Precious Stone
      Mountain' at 1.22 degrees N 101.49 degrees W. These specimens belonged to two new
      species of the obligately-vent-associated pycnogonid genus Sericosura. Three
      female specimens represent the new species Sericosura gemmaenonsis with large
      body size. One male and one female were of the second new species, Sericosura
      dentatus; the male specimen has a mid-dorsal femoral cement-gland-tube, like that
      of Sericosura dissita, while the female specimen has more finely-denticulate
      spines on the oviger strigilis than any other species of the genus.

PMID- 26312334
TI  - Zygonemella: the forgotten genus of the family Xyalidae (Nematoda).

PMID- 26312335
TI  - Classification of a clade of New World doves (Columbidae: Zenaidini).

PMID- 26312336
TI  - The advertisement call of Dendropsophus tritaeniatus (Bokermann, 1965) (Anura:
      Hylidae).

PMID- 26312337
TI  - The advertisement call of Phyllodytes gyrinaethes Peixoto, Caramaschi & Freire,
      2003 (Anura, Hylidae).

PMID- 26312338
TI  - Collaria columbiensis Carvalho, 1984, a newly recognized synonym of Collaria
      scenica (Stal, 1859) (Hemiptera: Heteroptera: Miridae).
AB  - The authors propose a new synonym between Collaria scenica (senior synonym) and
      Collaria columbiensis (junior synonym) based on external morphology and genitalia
      characteristics of male and female adults of both species. There was no
      significant difference found to believe that they are two different species.

PMID- 26312339
TI  - Contribution to the knowledge of Chinese Phasmatodea II: Review of the Dataminae
      Rehn & Rehn, 1939 (Phasmatodea: Heteropterygidae) of China, with descriptions of
      one new genus and four new species.
AB  - This paper deals with four genera and eight species of the subfamily Dataminae
      Rehn & Rehn, 1939 from China. One new genus and four new species, Hainanphasma
      cristata Ho gen. nov. spec. nov., H. diaoluoshanensis Ho spec. nov.,
      Pylaemenespui Ho spec. nov. and Pylaemenes shirakii Ho & Brock spec. nov., are
      described and illustrated. A new combination is proposed: Planispectrum
      hainanensis (Chen & He, 2008) comb. nov. is transferred from Pylaemenes Stal,
      1875 and its male and egg are described for the first time. The occurrence of
      Orestes mouhotii (Bates, 1865) in China is reconfirmed assessed by an adult
      specimen collected from Yunnan Province. Pylaemenes guangxiensis (Bi & Li, 1994)
      is reported for the first time from Vietnam outside the range of China. Keys to
      the genera and species of the Chinese Dataminae are given.

PMID- 26312340
TI  - An introduction to the systematics of Akodon orophilus Osgood, 1913 (Rodentia:
      Cricetidae) with the description of a new species.
AB  - The genus Akodon is one of the most species-rich rodent lineages in South
      America. In Peru, this genus contains 14 species subdivided in two groups:
      aerosus and boliviensis. Akodon orophilus Osgood, 1913 (Rodentia: Cricetidae) is
      a member of the Akodon aerosus group that inhabits the northern Peruvian montane
      forest, but is poorly characterized and its distribution is vaguely known. We
      review the status of the species based on morphology, morphometric and karyology,
      and compared with all members of the Akodon aerosus clade from Peruvian montane
      forests. As a result, we provide a complete redescription of A. orophilus,
      present new information on its natural history, restrict its distribution to the
      east of Rio Marai6n, and describe a new species of Akodon from Huanuco
      Department, central Peru, a population previously assigned to A. orophilus.

PMID- 26312341
TI  - Taxonomy of the genus Aporcelaimellus Heyns, 1965 (Nematoda, Dorylaimida,
      Aporcelaimidae).
AB  - The taxonomy of the genus Aporcelaimellus is revised and updated. A new
      definition is proposed, with several remarkable diagnostic characters: cuticle
      three-layered, especially distinguishable at caudal region, usually bearing a
      hyaline space between inner and intermediate layers at terminal portion of tail;
      cervical lacunae often present and well developed; oral aperture a dorso-ventral,
      hexagonal open slit; lip region showing bilateral symmetry and offset by a more
      or less distinct constriction; odontostyle short, robust and with wide aperture;
      uterus simple, bi- or tripartite; pars refringens vaginae present, well
      developed; tail similar in both sexes, short, rounded to conical with more or
      less rounded terminus; and ventromedian supplements 7-25 in number, separated,
      almost always with precloacal space (hiatus). A list of 28 valid species and
      their synonyms is provided as well as a key to their identification and a tabular
      compendium of their morphometrics. Aporcelainiellus faridpuriensis is considered
      to be a species inquirenda. Twenty-one species are regarded as incertae sedis: A.
      amplexor, A. budauniensis, A. canis, A. digicaudatus, Dorylaimus domus glauci, A.
      estonicus, A. gerlachi, A. goldeni, A. index, A. jairajpurii, A. monodelphus, A.
      nawabganjense, A. nivalis, A. paracentrocercus, A. paraobtusicaudatus, A.
      radicus,A. sacchari, A. seinhorsti, A. stilus, A. submissus and A. subsimilis.
      Two species are retained under other genera: A. bicuticulus under Labronema, and
      A. cocophilus under Aporcelaimus. Sixteen species are transferred to other
      genera: A. baqrii and A. odhneri to Crassolabium; A. dubius to Discolaimium as
      Discolaimium geraldi nom. n.; A. duhouxi to Labronema; A. glandus, A. heynsi, A.
      maitai and A. paraconicaudatus to Discolaimiun; A. insularis, A. jiaonanensis, A.
      kikereensis and A. propinquus to Aporcelinus; A. maximus to Aporcella; A.
      paracentrocercus apud Andrassy (1960) to Aporcelinus as Aporcelinus africanus sp.
      n.; A. saprophilus to Eudorylaimus; and A. tritici to Makatinus. Finally, A.
      concavus becomes a non-valid binomen.

PMID- 26312342
TI  - Two new species of Melanoplus Stal, 1873 (Orthoptera: Acrididae: Melanoplinae)
      from northeastern Mexico.
AB  - Two new species of the genus Melanoplus Stal 1873 are described. M. trachodes n.
      sp., and M. parvus n. sp., both of which are endemic to the cool-temperate
      mountains of the Eastern Sierra Madre (ESM) in northeastern Mexico. Their habitat
      represents a transition zone between the ESM and the semiarid High Plateau
      Biogeographic provinces. This transition zone is characterized by an elevation
      range from 1,900 to 3,400 m and unique ecological conditions, which give rise to
      a considerable number of endemisms.

PMID- 26312343
TI  - Revision of the Australian endemic ant genera Pseudonotoncus and Teratomyrmex
      (Hymenoptera: Formicidae: Formicinae).
AB  - The Australian endemic formicine ant genera Pseudonotoncus and Teratomyrmex are
      revised and their distributions and biologies reviewed. Both genera are limited
      to forested areas along the east coast of Australia. Pseudonotoncus is known from
      two species, P. eurysikos (new species) and P hirsutus (= P. turneri, new
      synonym), while Teratomyrmex is known from three species, T. greavesi, T.
      substrictus (new species) and T. tinae (new species). Distribution modelling was
      used to examine habitat preferences within the Pseudonotoncus species.

PMID- 26312344
TI  - Nepomorpha, Gerromorpha and Leptopodomorpha (Hemiptera: Heteroptera) of the
      Tuscan Archipelago (Italy).
AB  - This paper provides the first checklists for Nepomorpha (12 spp.), Gerromorpha
      (10 spp.) and Leptopodomopha (5 spp.) of the Tuscan Archipelago; summarizing and
      updating the knowledge for this area. The presence of the family Micronec- tidae
      is recorded for the first time in the Archipelago, as well as six species:
      Nepomorpha - Micronecta scholtzi (Fieber, 1860), Sigara selecta (Fieber, 1848),
      S. stagnalis (Leach, 1817), S. lateralis (Leach, 1817); Gerromorpha - Gerris
      asper (Fieber, 1860); Leptopodomorpha - Saldula palustris (Douglas, 1874);
      increasing the numbers of aquatic Heteroptera sensu lato from 21 to 27 species.
      The three infraorders are present in only four of the seven major islands of the
      Tuscan Archipelago (Capraia, Elba, Montecristo and Giglio). The Isle of Elba has
      been scarcely investigated until now: ten species are newly recorded for this
      island (doubling the number to 20 spp.), whilst another species has been first
      recorded for Giglio Island. The most remarkable finding is Gerris asper (Fieber,
      1860) on Elba, a species inhabiting marshy areas that is very rare to Italy.
      Notonecta glauca Linnaeus, 1758 is excluded from the fauna of the Tuscan
      Archipelago.

PMID- 26312345
TI  - The immature stages of Phylloicus lituratus (Trichoptera: Calamoceratidae) with
      new records of Phylloicus and Banyallarga species in northwestern Argentina and
      southern Bolivia.
AB  - Phylloicus lituratus Banks 1920 larva and pupa were associated. It is a new
      record for Argentina and represents the most austral record for the species. New
      records of other Calamoceratidae species are provided also from northwestern
      Argentina and southern Bolivia. Banyallarga (B.) argentinica Flint 1983 is
      recorded for the first time for Bolivia; B. (B.) loxana (Navds 1934) and B.(B.)
      yungensis Flint 1983 are both newly recorded from Salta province in northwestern
      Argentina. Illustrations of male genitalia of all species and of immature stages
      of P. lituratus are included. Presence of a Banyallarga larva in a leaf case
      suggests a need to change some larval keys used to identify the two endemic
      genera of Neotropical Calamoceratidae.

PMID- 26312346
TI  - Full title of manuscript: Five new species of the genus Hylaeus (Hymenoptera:
      Colletidae) from China.
AB  - Five new species, Hylaeus (Hylaeus) wuae sp. nov., H. (Hylaeus) napacus sp. nov.,
      H. (Hylaeus) neatifrons sp. nov., H. (Hylaeus) bimaculatus sp. nov. and Hylaeus
      (Prosopis) ikudomei sp. nov. are described and illustrated from Yunnan, China.
      The diagnosis of each species is provided. In addition, Hylaeus cardioscapus
      Cockerell, 1924 is recorded from China for the first time.

PMID- 26312347
TI  - New records of Pagurixus Melin, 1939 (Crustacea: Decapoda: Paguridae) from the
      Ryukyu Islands, southwestern Japan, with description of a new species.
AB  - Seven hermit crab species of the pagurid genus Pagurixus Melin, 1939 are reported
      on the basis of material recently collected from the northern and central islands
      of the Ryukyu Islands, southwestern Japan. Four species are new to the hermit
      crab fauna of the Ryukyu Islands: P. acanthocarpus Komai & Okuno, 2009; P.
      fasciatus Komai & Myorin, 2005; P. formosus Komai, 2010; and P. tweediei (Forest,
      1956). One species is described as new to science: P vicinus sp. nov. is closely
      similar to P. fasciatus in both morphology and coloration, but distinguished by
      the armature on the left cheliped and right second pereopod. Paguruxus
      carininanus Komai & Osawa, 2006 and P. pseliophorus Komai & Osawa, 2006, both
      previously known from the Ryukyu Islands, are here reported from new localities.

PMID- 26312348
TI  - Crangonidae and Glyphocrangonidae (Decapoda; Caridea) of the Southern Gulf of
      Mexico.
AB  - Distribution and abundance of species of Crangonidae and Glyphocrangonidae in the
      Mexican deep-waters of the Gulf of Mexico were analyzed through six research
      cruises onboard of the R/V Justo Sierra of the Universidad Nacional Autonoma de
      Mexico using an otter trawl in a depth range of 300-1200 m. We collected two and
      five species of the Crangonidae and Glyphocrangonidae families, respectively. We
      provide information about its depth and geographic distribution, abundance,
      frequency of occurrence and size structure. Glyphocrangon, composed of five
      species (G. aculeata, G. alispina, G. haematonotus, G. longleyi and G.
      spinicauda), was the most common and abundant component during the benthic trawls
      with a total of 1125 individuals. The family Crangonidae recorded only one genus
      and two species (Parapontocaris caribbaea and P vicina) with 21 individuals. A
      taxonomic key for these crangonid and glyphocrangonid shrimps of the Gulf of
      Mexico is also provided.

PMID- 26312349
TI  - Ivalia Jacoby--a flea beetle genus new to Australia (Coleoptera: Chrysomelidae:
      Galerucinae).
AB  - The genus Ivalia Jacoby, 1887 is recorded from Australia for the first time with
      descriptions of three new species, Ivalia reidi sp. nov., Ivalia iridescens sp.
      nov., and Ivalia lescheni sp. nov., from Queensland and New South Wales. A check
      list of 66 species of Ivalia and a key to the Australian species are provided.
      New replacement names proposed are Ivalia samuelsoni nom. nov. for Ivalia bella
      (Samuelson, 1966), a secondary homonym of Ivalia bella (Chen, 1934) and Ivalia
      gruevi nom. nov. for Ivalia castanea (Gruev, 1985a), a secondary homonym of
      Ivalia castanea (Samuelson, 1966).

PMID- 26312350
TI  - Taxonomic study of the genus Promalactis Meyrick, 1908 from Southeast Asia
      (Lepidoptera: Oecophoridae).
AB  - The genus Proinalactis Meyrick, 1908 is reviewed in Southeast Asia. Twenty-seven
      new species are described based on the specimens collected in Malaysia, Thailand,
      Brunei, Burma, Philippines. The new species include P. alveiformis sp. nov., P.
      angusta sp. nov., P. bruneiensis sp. nov., P. conicispinalis sp. nov., P.
      ellipsoidea sp. nov., P. exiliprocessa sp. nov., P. extumida sp. nov., P.
      fascisetacea sp. nov., P. flagellaris sp. nov., P. foraininulata sp. nov., P.
      fortijuxtalis sp. nov., P. lancea sp. nov., P. latuncata sp. nov., P.
      longisaccata sp. nov., P. lophacantha sp. nov., P. medispinata sp. nov., P.
      palmifolia sp. nov., P. pectinifera sp. nov., P.sectoralis sp. nov., P. semiovata
      sp. nov., P. sinualis sp. nov., P. spinosicostalis sp. nov., P. strena sp. nov.,
      P. superimposita sp. nov., P. truncatapicalis sp. nov., P. undulata sp. nov. and
      P. vulvida sp. nov. Promalactis parasuzukiella Wang, 2006 and P. simniliflora
      Wang, 2006 are recorded from Southeast Asia for the first time. Three species
      described by Lvovsky are fully redescribed. Images of adults and genitalia are
      provided, along with a check list of 71 species from Southeast Asia.

PMID- 26312351
TI  - Three new species of Aethes Billberg, 1820 (Lepidoptera: Tortricidae: Cochylini),
      with a list of the species from China.
AB  - The Chinese species of Aethes Billberg, 1820 are reviewed. Three species, A.
      acerba, sp. nov., A. semicircularis, sp. nov., and A. subcitreoflava, sp. nov.,
      are described, and A. fennicana (Hering, 1924) is newly recorded from China.
      Images of adults and genitalia of the new species and the newly recorded species
      are provided, along with a list, a key, and a distribution map to all the known
      Chinese species.

PMID- 26312352
TI  - Review of palaeozygopleurid gastropods (Palaeozygopleuridae, Gastropoda) from
      Devonian strata of the Perunica microplate (Bohemia), with a re-evaluation of
      their stratigraphic distribution, notes on their ontogeny, and descriptions of
      new taxa.
AB  - Review of all species of the family Palaeozygopleuridae Horny, 1955 (Gastropoda)
      known from the Perunica microplate (Bohemia) is presented with a description of
      three new species, Palaeozygopleura lukesi sp. nov., Cimrmaniela sveraki gen. et
      sp. nov. and Cimrmaniela smoljaki gen. et sp. nov. The stratigraphic
      distributions of the most of Bohemian palaeozygopleurid species are either
      corrected or refined, based on new records or modern stratigraphic studies. A
      complete list of the geographic occurrences of all known palaeozygopleurid
      gastropods from the Perunica microplate is also given together with notes on
      their ontogeny.

PMID- 26312353
TI  - A redescription of a rare axiid shrimp, Amakusaxius amakusanus (Miyake & Sakai,
      1967) (Crustacea: Decapoda: Axiidea) from new material collected off Taiwan.
AB  - Miyake & Sakai (1967) described a new species of axiid shrimp, Calocaris
      (Calastacus) amakusana, from a single female specimen lacking a major cheliped.
      Later, Sakai & de Saint Laurent, 1989 transferred this species to their new genus
      Acanthaxius. However, Sakai (2011) recently established a new monotypic genus
      Amakusaxius to accommodate Acanthaxius amakusana. Since the original description
      no additional specimen of this rare species has been reported and consequently an
      appraisal of A. amakusanus (Miyake & Sakai, 1967) has not been possible. Now six
      specimens including three males and three ovigerous females have been collected
      from Taiwan. This has enabled the diagnostic characters of the species to be
      fully evaluated. The presence of a postcervical median carina on the carapace,
      weak armature on the major cheliped, and the morphology of the uropod are
      characters that distinguish Amakusaxius from Acanthaxius. Consequently the
      monotypic genus Amakusaxius Sakai, 2011 is retained.

PMID- 26312354
TI  - New Calisto species from Cuba, with insights on the relationships of Cuban and
      Bahamian taxa (Lepidoptera, Nymphalidae, Satyrinae).
AB  - Three new species and a new subspecies of Calisto Hubner are described from Cuba,
      Calisto torrei sp. n. Nunez, Calisto dissimulatum sp. n. Nunez, Calisto aquilum
      sp. n. Nunez, and Calisto aquilum occidentalis ssp. n. Nunez. The immature stages
      of C. torrei and C. dissimulatum are also described. Notes on the distribution
      and biology of the species are given. All Cuban and Bahamian taxa form a
      monophyletic group which seems to have originated in northeastern Cuba spreading
      later to the west. DNA sequence data also allowed to recognize both Bahamian
      taxa, Calisto sibylla and Calisto apollinis stat. n., as distinct species, and to
      synonymize Calisto herophile parsonsi syn. n. under Calisto herophile.

PMID- 26312355
TI  - Taxonomic study of the cricket genus Valiatrella Gorochov (Gryllidae,
      Podoscirtinae) from China.
AB  - Four Valiatrella species, Valiatrella pulchra (Gorochov, 1985), Valiatrella
      sororia (Gorochov, 2002), Valiatrella laminaria Liu & Shi, 2007 and Valiatrella
      multiprotubera Liu & Shi, 2007, recorded from China are reviewed. A new species,
      Valiatrella persicifolius sp. nov., is described and illustrated.

PMID- 26312356
TI  - New species and records of the genus Trachypeplus Horvath (Hemiptera: Tingidae)
      from China.
AB  - This paper deals with the genus Trachypeplus from China. Nine species of
      Trachypeplus are treated in this paper, of which three species, namely
      Trachypeplus depressus sp. nov., Trachypeplus jingae sp. nov., and Trachypeplus
      parafulgoris sp. nov., are described as new. These nine species are photographed
      and keyed.

PMID- 26312357
TI  - Rediscovery of Sagittalarva inornata n. gen., n. comb. (Gilbert, 1890)
      (Perciformes: Labridae), a long-lost deepwater fish from the eastern Pacific
      Ocean: a case study of a forensic approach to taxonomy using DNA barcoding.
AB  - Some of the more valuable contributions of a standardized DNA sequence database
      (the DNA barcode) are matching specimens of different life stages and confirming
      the species identity of individuals from distant locations. These applications
      can facilitate the detective work required to solve difficult taxonomic problems.
      In this case, a match was made between the COI mtDNA sequence of an adult male
      wrasse recently caught at the tip of Baja California in Mexico in deep water (30
      100m) and sequences from a series of unusual larvae collected about 3500 km to
      the south, in the open ocean over the Galapagos Rift hydrothermal vents in 1985.
      The Baja adults fit the recent description of Halichoeres raisneri Baldwin &
      McCosker, 2001 from the Galapagos and Cocos Islands. However, another deepwater
      labrid is known from the same site and depth in Baja; it is the type locality for
      the century-old holotype and only specimen of the Cape Wrasse Pseudojulis
      inornatus Gilbert, 1890 (later as Pseudojuloides inornatus). Deepwater video
      images from the tip of Baja show wrasses identical to H. raisneri photographed in
      Galapagos but who also fit the description of Pseudojulis inornatus. This
      coincidence led to a closer investigation of the holotype with x-ray, which
      revealed unanticipated caniniform teeth (vs. incisiform in Pseudojuloides) and an
      error in the fin-ray count in the original description, both of which mistakenly
      separated Halichoeres raisneri. The two species now match in markings, meristics,
      and morphology as well as overlapping range and are therefore synonymized.
      Phenetic and phylogenetic trees using mtDNA and nuclear DNA sequences show the
      species is not close to any other lineage and does not group with the other
      julidine labrids of the New World or the Pseudojuloides or Halichoeres of the
      Indo-Pacific. The distinctive larval morphology, long, thin, and flattened with a
      sharply pointed black-tipped snout, resembles no other described labrid larvae
      and, without an available genus, the new genus Sagittalarva Victor, n. gen. and
      the new combination Sagittalarva inornata (Gilbert, 1890), n. gen., n. comb. are
      described.

PMID- 26312358
TI  - A giant foraminifer that converges to the feeding strategy of carnivorous
      sponges: Spiculosiphon oceana sp. nov. (Foraminifera, Astrorhizida).
AB  - The foraminifer Spiculosiphon oceana sp. nov. is a giant (>4 cm) agglutinated
      astrorhizid, which makes the second known species of this unusual genus and its
      first Mediterranean record. It has a peculiar stalked, capitate, monothalamous
      test. Bleach digestion and X-ray microanalysis indicated the test to be made
      exclusively of siliceous sponge spicules agglutinated in organic cement. The
      organism stands on a hollow, 4 cm long, 0.5 cm thick stalk built with highly
      selected, long and thin spicule fragments, tightly cemented together in parallel
      to the main axis of the stalk. The proximal end of the stalk is closed and
      slightly expanded into a bulb-like structure, designed to penetrate between the
      sand grains and maintaining the test upright while avoiding a permanent
      attachment to the substratum. The distal stalk end becomes a hollow, globe-like
      structure that contains the main protoplasm. The globelike region is built with
      loosely agglutinated and irregularly-shaped spicules, allowing extrusion of the
      pseudopodia through the cavities between the spicules. The globelike structure
      also serves as an anchoring basis, from which long and thin, solid tracts
      protrude radially to make a spherical crown that attains about 4 mm in total
      diameter. The radiating tracts are built with highly selected aciculate spicule
      fragments held together with a translucent organic cement. They provide skeletal
      support for the extension of a crown of pseudopodia into the water column. This
      arrangement is thought to enhance the chances of the pseudopodia to contact
      demersal planktonic prey. In summary, Spiculosiphon species collect and arrange
      sponge spicules with high selectivity to recreate a body morphology that strongly
      converges to that of some carnivorous sponges, which allows these predatory
      foraminifera to exploit a prey capturing strategy similar to that of the
      carnivorous sponges. This idea is also consistent with our report of an
      additional, yet undetermined, Spiculosiphon species occurring in the same
      sublittoral Mediterranean cave where carnivorous sponges were first discovered.

PMID- 26312360
TI  - Type specimens of Anthus berthelotii Bolle, 1862 (Aves: Motacillidae).

PMID- 26312359
TI  - Ephedraphis Hille Ris Lambers (Hemiptera: Aphididae), with a key to species and
      one new species from Mongolia.
AB  - The aphid genus Ephedraphis Hille Ris Lambers is reviewed. The genus is
      represented by four species, including Ephedraphis mongolica sp. n. on Ephedra
      sp. from Umnogovi Province, Mongolia. A key to the known species of Ephedraphis
      is provided. Diagnostic characters of all species are given. All specimens
      studied, including type specimens are deposited in the National Zoological Museum
      of China, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

PMID- 26312370
TI  - ATF5 is an essential protein in the centrosome.

PMID- 26312371
TI  - Reduction and transformation of fluorinated graphene induced by ultraviolet
      irradiation.
AB  - The effect of ultraviolet irradiation on fluorinated graphene (FG) dispersed in
      toluene was investigated for the first time. The chemical and physical
      characteristics of FG before and after ultraviolet irradiation were analyzed by
      UV-vis, FTIR, XPS,EDS, oxygen flask combustion (OFC), XRD, TGA, Raman, SEM, TEM
      and fluorescence spectroscopy. It is found that the F/C ratio initially decreases
      rapidly and then slowly with irradiation time, finally to 0.179 after irradiation
      for 48 h. The nature of partial C-F bonds transforms from covalent to "semi
      covalent" bonding in the process of irradiation. The restoration of new sp(2)
      clusters is fast at the early stage within 6 h of irradiation, promoting the
      structural rearrangement. The morphology of irradiated fluorinated graphene (iFG)
      is not significantly destroyed by ultraviolet while more overlapped sheets are
      formed due to quick defluorination. Photoluminescence (PL) properties show that
      "blue emission" located at 432 nm is enhanced due to the recovery of sp(2)
      domains. In particular, compared to non-aromatic solvents, there is a
      "synergistic effect" between aromatic solvents and ultraviolet in the
      defluorination process. FG is unstable and shows some structural transformations
      under ultraviolet irradiation, which can be used to tune its structure and
      properties. 

PMID- 26312372
TI  - [Dogs as a possible source of human Campylobacter infecfions].
AB  - OBJECTIVES: The aims of this study were to obtain current information on the
      prevalence and species representation of bacteria of the genus Campylobacter in
      dogs in Moravia and to evaluate the risk factors affecting their occurrence with
      respect to possible transmission to the human population. MATERIAL AND METHODS:
      Rectal swabs of dogs obtained in the routine practice of veterinarians in the
      South Moravian and Olomouc -regions were examined from May 2013 to December 2014.
      The basic tests were performed in laboratories of the State Veterinary Institute
      in Olomouc and the University of Veterinary and Pharmaceutical Sciences Brno. To
      detect Campylobacter spp., the samples were cultured on mCCDA (modified charcoal
      cefoperazone-deoxycholate agar). Suspected colonies were confirmed by MALDI-TOF
      MS (Biotyper Microflex, Bruker) or using specific PCR which allows to distinguish
      between the species C. jejuni, C. coli, C. lari and C. upsaliensis. A detailed
      history was obtained from questionnaires completed by the dog owners. RESULTS:
      From a total of 258 rectal swabs examined, 41 samples were positive (16 %). The
      most frequently detected species was C. jejuni, followed by C. upsaliensis a C.
      coli. There was only one sample of C. lari. The evaluation of the questionnaire
      data showed that the frequency of Campylobacter spp. and their species
      representation depended on the age of the animals, the composition of feed and
      the clinical signs of the disease. CONCLUSION: Young dogs on a homemade diet and
      with diarrhea may be considered a risk group in terms of possible transmission of
      Campylobacter infections from pets to humans. Households with young children are
      the most affected group in the Czech Republic and EU countries. As such, they
      should be given a high priority with respect to the basic hygiene rules if they
      breed dogs, especially puppies.

PMID- 26312373
TI  - [Prevalence and characteristics of MRSA strains isolated from pigs on farms, at
      slaughterhouses and in pork meat at retail sale in the Czech Republic].
AB  - OBJECTIVES: To detect and characterize strains of methicillin-resistant
      Staphylococcus aureus (MRSA) on pig farms, at slaughterhouses and meat samples at
      retail sale. MATERIAL AND METHODS: A total of 890 samples were examined in the
      years 2013-2015, comprising 59 samples from primary production (pig farms), 463
      swabs from processing plants (slaughterhouses) and 368 samples of pork meat and
      liver collected at retail sale. The culture method was used for the detection of
      MRSA. After homogenization, the samples were enriched in buffered peptone water
      at 37  degrees C for 18-24 hours and two-stage selective enrichment was
      performed. Five milliliters of PPV were transferred to Mueller-Hinton medium with
      addition of 6.5 % NaCl and after incubation at 37  degrees C for 18-24 hours, 1
      ml was inoculated into tryptone soy broth with cefoxitin and aztreonam. The
      suspension was plated onto Baird-Parker and BrillianceTM MRSA 2 agar on the next
      day. Suspected colonies were confirmed by PCR, the specific S. aureus fragment
      SA442, the mecA gene encoding resistance to methicillin and relation to the
      clonal complex CC398 were detected. Further, resistance test to a panel of 11
      antimicrobial agents using the disk diffusion method was performed. RESULTS:
      Within this study, 51 MRSA strains were obtained, of which 15 originated from
      live pigs, 31 isolates were from slaughterhouses and 5 were detected in retail
      samples. Forty-seven (92.2 %) MRSA strains belonged to the clonal complex CC398.
      Four non-CC398 isolates were obtained from two slaughterhouses and came from
      three farms. The strains often showed multiple resistance. In some MRSA isolates,
      resistance to erythromycin (36; 70.6 %), tetracycline (29; 56.9 %),
      fluoroquinolones (7; 13.7 %), co-trimoxazole (6; 11.8 %) and aminoglycosides (4;
      7.8 %) was detected. CONCLUSION: MRSA isolates of the clonal complex CC398
      dominate in foods of animal origin. These strains originate from livestock and
      are often characterized by multiple resistance to antimicrobials. The role of the
      food chain in the spread of LA-MRSA is not yet clearly understood.

PMID- 26312374
TI  - [Identification of zoonotic bacterial pathogens by the MALDI TOF MS method].
AB  - OBJECTIVE: To verify whether the MALDI TOF MS method can be used for rapid
      identification of selected zoonotic bacterial pathogens isolated from various
      types of materials in the real conditions of routine laboratory work. MATERIAL
      AND METHODS: Between August 2010 and April 2015, the Bruker's MALDI TOF MS system
      was used for 4,174 identifications of selected zoonotic bacterial pathogens
      (Salmonella spp., Campylobacter jejuni, Campylobacter coli, Listeria
      monocytogenes, Yersinia enterocolitica, Yersinia pseudotuberculosis, Francisella
      tularensis, Brucella melitensis, Brucella suis and Cronobacter sakazakii). The
      samples were prepared for the test by simply mixing a bacterial culture with a
      matrix on a steel target plate. The results were evaluated with a standard
      protocol of the system using the MALDI Biotyper software under operating
      conditions. RESULTS: In 74.8 % of the tested isolates of the above bacterial
      species, the identification scores ranged between 2 and 3, which is satisfactory
      for result interpretation in routine practice. Acceleration of identification of
      Campylobacter spp. and Listeria monocytogenes by testing suspicious cultures
      obtained directly from selective-diagnostic media decreased the identification
      scores in these cases. CONCLUSION: MALDI TOF MS is a suitable and rapid method
      for identification of the selected zoonotic bacterial pathogens.

PMID- 26312375
TI  - [Invasive Pasteurella multocida infections: Two clinical cases and literature
      review].
AB  - Pasteurella multocida is a common commensal of the gastrointestinal and
      respiratory tracts of animals, especially cats and dogs. It is transmitted to
      humans through contact with animals. Bite wound infection is the most common
      clinical manifestation. Systemic infections are unusual and mainly affect
      immunocompromised individuals. The article presents two cases of Pasteurella
      infection. Wound infection in a 75-year-old female following a bite from her pet
      cat was associated with bacteremia. The disease course was favorable with the
      initial clindamycin treatment despite in vitro resistance. The other patient was
      a 62-year-old female diagnosed with acute bacterial meningitis with multiple
      brain abscesses and transient expressive aphasia. She reported frequent contacts
      with pets and domestic animals without a recent bite. Hematogenous dissemination
      of the infection was suspected. Because of poor therapeutic response, cefotaxime
      was switched to chloramphenicol which was later switched to a combination of
      cefotaxime with ciprofloxacin due to anemia. Following 6 weeks of intravenous
      antibiotic therapy and another 10 weeks of oral ciprofloxacin therapy, magnetic
      resonance imaging showed normal results and the neurological defect resolved.
      Epidemiological, clinical and therapeutic aspects of Pasteurella infection are
      discussed and literature is reviewed. 

PMID- 26312376
TI  - [Bovine tuberculosis still not to be forgotten even in the Czech Republic].
AB  - Bovine tuberculosis is caused by two obligate pathogenic species, Mycobacterium
      bovis and M. caprae, that cause severe disease in animals and humans. The oral
      route of infection causing extrapulmonary forms of the disease in humans is more
      common than aerogenic infection causing pulmonary tuberculosis. Significant risk
      factors for the development of diseases in humans are mainly consuming
      insufficiently heat-treated milk or meat from infected animals. Since 2004, the
      Czech Republic has been listed among the EU countries that are officially free of
      bovine tuberculosis in cattle. In light of the increasing numbers of other animal
      species (esp. red deer and wild boars) infected with bovine tuberculosis in
      neighboring countries, it is necessary to draw attention to this situation. 

PMID- 26312377
TI  - Minimally Invasive Repair of Pectus Excavatum Without Bar Stabilizers Using Endo
      Close.
AB  - OBJECTIVES: Since the introduction of the Nuss technique for pectus excavatum
      (PE) repair, stabilization of the bar has been a matter of debate and a crucial
      point for the outcome, as bar dislocation remains one of the most frequent
      complications. Several techniques have been described, most of them including the
      use of a metal stabilizer, which, however, can increase morbidity and be
      difficult to remove. Our study compares bar stabilization techniques in two
      groups of patients, respectively, with and without the metal stabilizer. SUBJECTS
      AND METHODS: A retrospective study on patients affected by PE and treated by the
      Nuss technique from January 2012 to June 2013 at our institution was performed in
      order to evaluate the efficacy of metal stabilizers. Group 1 included patients
      who did not have the metal stabilizer inserted; stabilization was achieved with
      multiple (at least four) bilateral pericostal Endo CloseTM (Auto Suture, US
      Surgical; Tyco Healthcare Group, Norwalk, CT) sutures. Group 2 included patients
      who had a metal stabilizer placed because pericostal sutures could not be used
      bilaterally. We compared the two groups in terms of bar dislocation rate,
      surgical operative time, and other complications. Statistical analysis was
      performed with the Mann-Whitney U test and Fisher's exact test. RESULTS: Fifty
      seven patients were included in the study: 37 in Group 1 and 20 in Group 2. Two
      patients from Group 2 had a bar dislocation. Statistical analysis showed no
      difference between the two groups in dislocation rate or other complications.
      CONCLUSIONS: In our experience, the placement of a metal stabilizer did not
      reduce the rate of bar dislocation. Bar stabilization by the pericostal Endo
      Close suture technique appears to have no increase in morbidity or migration
      compared with the metal lateral stabilizer technique.

PMID- 26312378
TI  - CRB1-Related Maculopathy With Cystoid Macular Edema.

PMID- 26312379
TI  - Chemical Considerations for an Updated National Assessment of Brackish
      Groundwater Resources.
AB  - Brackish groundwater (BGW) is increasingly used for water supplies where fresh
      water is scarce, but the distribution and availability of such resources have not
      been characterized at the national scale in the United States since the 1960s.
      Apart from its distribution and accessibility, BGW usability is a function of the
      chemical requirements of the intended use, chemical characteristics of the
      resource, and treatment options to make the resource compatible with the use.
      Here, we discuss relations between these three chemical factors using national
      scale examples and local case studies. In a preliminary compilation of BGW data
      in the United States, five water types accounted for the major-ion composition of
      70% of samples. PHREEQC calculations indicate that 57-77% of samples were
      oversaturated with respect to barite, calcite, or chalcedony. In the study, 5-14%
      of samples had concentrations of arsenic, fluoride, nitrate, or uranium that
      exceeded drinking-water standards. In case studies of the potential use of BGW
      for drinking water, irrigation, and hydraulic fracturing, PHREEQC simulations of
      a hypothetical treatment process resembling reverse osmosis (RO) showed that BGW
      had the potential to form various assemblages of mineral deposits (scale) during
      treatment that could adversely affect RO membranes. Speciation calculations
      showed that most boron in the irrigation example occurred as boric acid, which
      has relatively low removal efficiency by RO. Results of this preliminary study
      indicate that effective national or regional assessments of BGW resources should
      include geochemical characterizations that are guided in part by specific use and
      treatment requirements.

PMID- 26312380
TI  - Lack of Healthy Food in Small-Size to Mid-Size Retailers Participating in the
      Supplemental Nutrition Assistance Program, Minneapolis-St. Paul, Minnesota, 2014.
AB  - INTRODUCTION: The US Department of Agriculture has stocking criteria for healthy
      foods among Supplemental Nutrition Assistant Program (SNAP)-authorized retailers.
      Increased access to healthy food could improve diet quality among SNAP
      participants, which has implications for chronic disease prevention. The
      objective of this study was to quantify healthy foods stocked in small-size to
      mid-size retailers who are authorized under SNAP but not under the Special
      Supplemental Nutrition Program for Women, Infants, and Children (WIC). METHODS:
      We used formative, cross-sectional data from a large policy evaluation to conduct
      secondary analyses. Store audits were conducted in 2014 in 91 randomly selected,
      licensed food stores in Minneapolis and St. Paul, Minnesota. Supermarkets and
      retailers participating in WIC, which are required to stock healthy foods, were
      excluded as were other stores not reasonably expected to stock staple foods, such
      as specialty stores or produce stands. Availability of milk, fruits, vegetables,
      and whole-grain-rich foods was assessed. RESULTS: The 91 stores studied were
      corner stores, food-gas marts, dollar stores, and pharmacies. More than half
      carried 1 or more varieties of fat-free or low-fat milk, fresh or canned fruit,
      and whole-grain-rich cereal. However, only one-third stocked 1 or more varieties
      of fresh vegetables and only one-quarter stocked whole-grain-rich products, such
      as whole-grain-rich bread (26%) or tortillas (21%) or brown rice (25%). Few
      stores stocked at least 2 varieties of each product. CONCLUSIONS: Many stores did
      not stock a variety of healthy foods. The US Department of Agriculture should
      change policies to improve minimum stocking requirements for SNAP-authorized
      retailers.

PMID- 26312381
TI  - Critical Elements of a School Report to Parents on Body Mass Index.
AB  - School-based body mass index (BMI) screening and reporting could have a positive
      impact on student health, but best practices for writing a report are unknown.
      Building on previous qualitative work, 8 focus groups were conducted with a
      diverse group of California parents (n = 79) to elicit feedback on report content
      and design. Results indicate that parents want a visually appealing, picture
      heavy report that clearly defines BMI, avoids stigmatizing language, and includes
      recommendations for appropriate actions whole families can take. Next steps
      involve using the final report in a statewide, randomized trial to determine the
      effectiveness of school-based BMI screening and reporting in reducing childhood
      obesity. 

PMID- 26312382
TI  - Assessing a Public Health Intervention for Children in Barbados, 2003-2008.
AB  - INTRODUCTION: In 2003, Barbados, a developing country with universal health care,
      launched the Barbados Strategic Plan for Health, a national intervention to
      promote public health. Teachers, health educators, and clinicians worked to
      improve children's health, with particular focus on asthma and diabetes. We
      studied this intervention by using data on preventable hospitalization, an
      indicator that assesses both the overall effectiveness of public health and
      access to primary health care. The purpose of this study was to assess the
      Barbados Strategic Plan for Health by measuring rates of preventable
      hospitalization among children. Few researchers have studied these
      hospitalizations for children, and only 1 study has done so in a developing
      country. METHODS: We calculated annual (2003-2008) population-based rates of
      preventable hospitalizations from birth through age 19, both summary and disease
      specific, for the 5 conditions that define the indicator for children: asthma,
      diabetes, gastroenteritis, urinary tract infection, and perforated appendix.
      RESULTS: Across the 6 years, the population rates of preventable hospitalizations
      increased 115.4% for boys and 67.2% for girls (both P < .001). Asthma accounted
      for much of the increase. Regression analysis indicated that the average annual
      increase in asthma hospitalization for boys was 0.45 per 1,000, an average annual
      increase of 20.6% of the baseline rate. These results suggest generally
      increasing rates of hospitalization for asthma for boys. There was no evidence of
      a corresponding rate trend for girls. CONCLUSION: Results suggest an opportunity
      to improve public health education and access to primary health care. Public
      health professionals in developing countries can use the approaches of this study
      to evaluate initiatives to improve child health.

PMID- 26312383
TI  - Effect of Family Income on the Relationship Between Parental Education and
      Sealant Prevalence, National Health and Nutrition Examination Survey, 2005-2010.
AB  - INTRODUCTION: We examined the association between sealant prevalence and parental
      education for different levels of family income, controlling for other
      covariates. METHODS: We combined data from 2005-2006, 2007-2008, and 2009-2010
      cycles of the National Health and Nutrition Examination Survey. The study sample
      was 7,090 participants aged 6 to 19 years. Explanatory variables, chosen on the
      basis of Andersen and Aday's framework of health care utilization, were
      predisposing variables - child's age, sex, race/ethnicity, and parental education
      (<high school diploma; high school diploma; >high school diploma); enabling
      variables - family income (<100% of the federal poverty level [FPL]; 100%-200% of
      the FPL; and >200% of the FPL), health insurance status, and regular source of
      medical care; and a need variable - future need for care (perceived child health
      status is excellent/very good, good, fair/poor). We conducted bivariate and
      multivariate analyses and included a term for interaction between education and
      income in the multivariate model. We report significant findings (P <= .05).
      RESULTS: Sealant prevalence was associated with all explanatory variables in
      bivariate and multivariate analyses. In bivariate analyses, higher parental
      education and family income were independently associated with higher sealant
      prevalence. In the multivariate analysis, higher parental education was
      associated with sealant prevalence among higher income children, but not among
      low-income children (<100% FPL). Sealant prevalence was higher among children
      with parental education greater than a high school diploma versus less than a
      high school diploma in families with income >=100% FPL. CONCLUSION: Our findings
      suggest that income modifies the association of parental education on sealant
      prevalence. Recognition of this relationship may be important for health
      promotion efforts.

PMID- 26312384
TI  - Adherence to and persistence with non-vitamin K-antagonist oral anticoagulants:
      does the number of pills per day matter?
AB  - Once daily dosing schedule is associated with increased adherence to and
      persistence with cardiovascular therapies. Such feature has been claimed
      responsible for the significantly lower (both temporary and permanent)
      discontinuation of oral anticoagulation with rivaroxaban (which is given once
      daily) compared to dabigatran (which is given twice daily) in a large, real-world
      dataset of patients with atrial fibrillation (AF) in the United States. While a
      cause-effect relationship between dosing schedule and adherence and persistence
      could not be established, the above finding supports nonetheless the preferential
      selection of the non vitamin-K-antagonists oral anticoagulant (NOAC) with the
      easiest and most convenient regimen. Given however, the differences in efficacy
      and safety observed with the various NOACs compared to warfarin in the phase III
      clinical trials in non-valvular AF, careful individualization of treatment should
      be pursued, being dosing schedule only one of the variables to be taken into
      account. Maximal effort instead, should be put in implementing measures to
      enhance patient's adherence to and persistence with treatment. 

PMID- 26312385
TI  - Omalizumab therapy for children and adolescents with severe allergic asthma.
AB  - Omalizumab, a therapeutic humanized monoclonal antibody specific for human IgE,
      was introduced in clinical practice more than a decade ago as an add-on therapy
      for moderate-to-severe allergic asthma in patients aged >=12 years. Omalizumab
      has been demonstrated to be effective in adults with uncontrolled persistent
      asthma, with an excellent safety profile. In simple terms, omalizumab works by
      inhibiting the allergic cascade, that is, by neutralization of the circulating
      free IgE. This leads to reduction in the quantity of cell-bound IgE,
      downregulation of high-affinity IgE receptors, and, eventually, prevention of
      mediator release from effector cells. Evidence is far less abundant on the role
      of omalizumab in pediatric asthma. Although efficacy and safety of omalizumab in
      children and adolescents with uncontrolled, persistent allergic asthma has been
      recognized as well, further studies are needed to clarify a number of open
      questions in this specific patient population. 

PMID- 26312386
TI  - Resistance to sunitinib in renal clear cell carcinoma results from sequestration
      in lysosomes and inhibition of the autophagic flux.
AB  - Metastatic renal cell carcinomas (mRCC) are highly vascularized tumors that are a
      paradigm for the treatment with antiangiogenesis drugs targeting the vascular
      endothelial growth factor (VEGF) pathway. The available drugs increase the time
      to progression but are not curative and the patients eventually relapse. In this
      study we have focused our attention on the molecular mechanisms leading to
      resistance to sunitinib, the first line treatment of mRCC. Because of the
      anarchic vascularization of tumors the core of mRCC tumors receives only
      suboptimal concentrations of the drug. To mimic this in vivo situation, which is
      encountered in a neoadjuvant setting, we exposed sunitinib-sensitive mRCC cells
      to concentrations of sunitinib below the concentration of the drug that gives 50%
      inhibition of cell proliferation (IC50). At these concentrations, sunitinib
      accumulated in lysosomes, which downregulated the activity of the lysosomal
      protease CTSB (cathepsin B) and led to incomplete autophagic flux. Amino acid
      deprivation initiates autophagy enhanced sunitinib resistance through the
      amplification of autolysosome formation. Sunitinib stimulated the expression of
      ABCB1 (ATP-binding cassette, sub-family B [MDR/TAP], member 1), which
      participates in the accumulation of the drug in autolysosomes and favor its
      cellular efflux. Inhibition of this transporter by elacridar or the
      permeabilization of lysosome membranes with Leu-Leu-O-methyl (LLOM) resensitized
      mRCC cells that were resistant to concentrations of sunitinib superior to the
      IC50. Proteasome inhibitors also induced the death of resistant cells suggesting
      that the ubiquitin-proteasome system compensates inhibition of autophagy to
      maintain a cellular homeostasis. Based on our results we propose a new
      therapeutic approach combining sunitinib with molecules that prevent lysosomal
      accumulation or inhibit the proteasome. 

PMID- 26312387
TI  - Preserved cutaneous silent period in cervical root avulsion.
AB  - OBJECTIVE: Brachial plexus injuries are usually severe and involve the entire
      brachial plexus, sometimes occurring with root avulsions. Imaging and
      electrodiagnostic studies are an essential part of the lesion evaluation;
      however, the results sometimes show a discrepancy. The cutaneous silent period
      (SP) is a spinal inhibitory reflex mediated by small-diameter A-delta nociceptive
      fibers. The aim of the study was to determine if cutaneous SP testing may serve
      as a useful aid in evaluation of brachial plexus injury and/or in the diagnosis
      of root avulsion. METHODS: In 19 patients with traumatic brachial plexus injury
      (15 males, age 18-62 years) we performed a clinical examination, CT myelography
      and neurophysiological testing. A needle EMG was obtained from muscles supplied
      by C5-T1 myotomes. Cutaneous SP was recorded after painful stimuli were delivered
      to the thumb (C6 dermatome), middle (C7) and little (C8) fingers while subjects
      maintained voluntary contraction of intrinsic hand muscles. RESULTS:
      Electrodiagnostic and imaging studies confirmed root avulsion (partial or total)
      maximally involving C5, C6 roots in 12 patients, whereas only in 4 of them the
      cutaneous SP was partially absent. In the remaining subjects, the cutaneous SP
      was preserved. CONCLUSION: In brachial plexopathy even with plurisegmental root
      avulsion, the cutaneous SP was mostly preserved. This method cannot be
      recommended as a reliable test for diagnosis of single root avulsion; however, it
      can provide a quick physiological confirmation of functional afferent A-delta
      fibers through damaged roots and/or trunks. The clinicians may add this test to
      the diagnosis of spinal cord dysfunction.

PMID- 26312388
TI  - [Fetal growth: the dilemma of multiple references].

PMID- 26312389
TI  - [HLA alleles association and recurrent spontaneous abortion in a Sao
      Luis/Maranhao population, in Brazilian Northeastern region].
AB  - PURPOSE: To investigate the association of the HLA-A, -B and -DRB1 alleles with
      the occurrence of Recurrent Spontaneous Abortion. METHODS: A case-control study
      of 200 women aged 18 to 35 years, consisting of a convenience sample of 100 women
      who had idiopathic recurrent spontaneous abortion and 100 women without abortion
      and with two or more children. Peripheral blood genomic DNA was extracted from
      500l of Buffy Coat stored at -20 degrees C. HLA typing was performed by the PCR
      SSOP method (Polymerase Chain Reaction - Specific Sequence of Oligonucleotides
      Probes, One Lambda(r), CA, USA). The regions of the amplified DNA were exon 2 and
      3 for the A and B loci and only exon 3 for the DRB1 locus. The HLA FUSIONTM
      program (One Lambda, Canoga Park, CA, USA, version 3.0) was used for HLA-A, HLA-B
      and HLA-DRB1 genotyping. Absolute frequencies and percentages and calculation of
      mean and standard deviation were used for standard statistical analysis. The
      qualitative variables were compared by the chi2 test with Yates correction or by
      Fisher's exact test. The odds ratio with the 95%CI was used for the comparisons,
      with the level of significance set at p<0.05. RESULTS: The frequency of the A*34
      allele was significantly higher in the case group compared to control (4.0 versus
      0.5%; p<0.05). Alleles A*24 (6.0 versus 12.5%; p<0.05) and B*35 (8.0 versus
      20.5%; p<0.05) were significantly less frequent in the case group. Among the
      class II alleles, DRB1*03 showed a slightly higher frequency in the case group
      (11.0 versus 5.5%, p = 0.056). CONCLUSIONS: It was shown that the HLA-A*34 allele
      is a risk factor for recurrent spontaneous abortion, while the HLA-A*24 and HLA
      B*35 alleles are associated with protection, and no allele of the DRB1 locus was
      associated with RSA.

PMID- 26312390
TI  - [Preterm birth susceptibility: investigation of behavioral, genetic, medical and
      sociodemographic factors].
AB  - PURPOSE: To investigate the association between genetic, behavioral, biological
      and medical risk factors and the occurrence of preterm birth. METHODS: A
      retrospective case-control study was conducted. The real-time polymerase chain
      reaction was used to analyze the influence of the rs12473815 polymorphism of the
      follicle stimulating hormone receptor gene (FSHR) and the rs1942836 polymorphism
      of the progesterone receptor gene (PGR). Other proposed risk factors were
      assessed using validated or specifically developed questionnaires and analysis of
      electronically recorded medical data. A total of 157 patients were included (45
      cases who went into labor before 37 weeks of pregnancy and 112 controls who went
      into labor after 37 and before 42 weeks of pregnancy). RESULTS: The genotypes CT
      of rs12473815 and CT and CC of rs1942836 were associated with a higher chance of
      premature delivery. There was an association between preterm birth and alcohol
      intake when consumption occurred 2 or more times per month. Low pre-pregnancy
      body mass index was a predictor of spontaneous preterm birth, while high body
      mass index reduced this likelihood. CONCLUSIONS: The results suggest that
      excessive alcohol intake, a low level of pre-pregnancy body mass and the risk
      alleles of rs12473815 and rs1942836 polymorphisms of the FSHR and PGR genes,
      respectively, influence the occurrence of preterm birth.

PMID- 26312391
TI  - [Sleep quality in overweight pregnant women].
AB  - PURPOSE: To compare sleep quality of overweight versus normal weight women in the
      second and third trimesters of pregnancy. METHODS: A cross-sectional study
      involving 223 women with 14 or more weeks of pregnancy, 105 of them overweight
      (pre-pregnancy body mass index - BMI - >=25.0 kg/m2) and 118 of normal weight
      (BMI 18.5-24.9 kg/m2), attending the prenatal care clinic. The Brazilian version
      of the Pittsburgh Sleep Quality Index (PSQI-BR) questionnaire was used to
      evaluate sleep quality. The Student t-test and the chi-square test were used to
      compare differences between groups and a p value <0.05 was considered
      statistically significant. RESULTS: Most of the participants (67.7%) were poor
      sleepers (total score >5); this proportion was significantly higher among
      overweight (80/105) versus normal weight (67/118) women (76.2 versus 56.8%,
      p=0,004). During the second trimester, this difference did not reach statistical
      significance (72.5 versus 53.7%, respectively, p=0.06) but mean total PSQI-BR
      scores were significantly higher among overweight participants (7.0+/-3.8 versus
      5.5+/-3.2, p=0.02). In the 2nd trimester, overweight women also had higher scores
      for sleep latency (1.4+/-1.0 versus 1.0+/-0.9, p=0.02) and subjective sleep
      quality (1.3+/-0.8 versus 0.8+/-0.8, p=0.02). In the third trimester, the
      proportion of women with poor sleep quality was significantly higher in the
      overweight group, but did not reach statistical significance (79.6 versus 60.8%,
      p=0.06). During this period, total mean scores were similar for women with and
      without excess weight (9.4+/-4.2 versus 8.3+/-4.6, p=0.2). However, overweight
      women had higher mean scores for sleep disturbance (2.3+/-0.7 versus 2.0+/-0.8,
      p=0.04). CONCLUSION: Overweight women had a poorer sleep quality than normal
      weight women in the second and third trimesters of pregnancy.

PMID- 26312392
TI  - Spatial distribution of pregnancy in adolescence and associations with
      socioeconomic and social responsibility indicators: State of Minas Gerais,
      Southeast of Brazil.
AB  - PURPOSE: To describe associations between pregnancy rates in adolescence and
      socioeconomic and social responsibility indicators in the municipalities of the
      State of Minas Gerais, Southeast of Brazil, in the year of 2010. METHODS:
      Ecological study using data from the Brazilian Live Birth Information System
      (SINASC). The percentage of live births to adolescent mothers (LBAM) for each
      municipality was calculated based on the quotient between number of born alive
      infants of mothers aged 10-19 years old and total number of live births in the
      year of 2010. Fully Bayesian models were used to obtain the percentages of LBAM
      adjusted for spatial effects and to assess possible associations with
      socioeconomic and social responsibility indicators. RESULTS: The crude percentage
      of LBAM for the total number of live births in the municipalities of Minas Gerais
      in 2010 ranged from 0 to 46.4%, with median percentage being 19.6% and the first
      and third quartiles being 15.6 and 23.1%, respectively. This study has
      demonstrated a close relationship between adolescent pregnancy and socioeconomic
      indicators. LBAM percentages were found to be higher in municipalities with low
      population density, low human development index and other low development
      indicators. CONCLUSION: The strong relationship between LBAM percentages and
      socioeconomic indicators suggests that adolescent pregnancy is more a social than
      a biological problem. Therefore, programs and actions should go beyond sexual
      education and information on preventive health methods.

PMID- 26312393
TI  - [Effect of the type of urinary incontinence on the quality of life of patients in
      the public healthcare system in Southeastern Brazil].
AB  - PURPOSE: To identify the impact of urinary incontinence (UI) on quality of life
      (QoL), to compare the scores of QoL domains in women with stress urinary
      incontinence (SUI), overactive bladder (OAB) and mixed incontinence (MUI) and to
      establish the association between the clinical type of UI and the impact on QoL.
      METHODS: Data of 181 incontinent women attended at a public hospital were
      collected regarding age, body mass index (BMI) and co-morbidities. King's Health
      Questionnaire (KHQ) was applied and patients were classified into two groups
      according to the self-assessment of incontinence impact. KHQ scores were compared
      by the Mann-Whitney test. Depending on their urinary symptoms, women were divided
      into SUI, OAB and MUI groups and their scores in the KHQ domains were compared by
      the Kruskal-Wallis and Dunn tests. The odds ratio (OR) of a woman reporting a
      worse effect of UI on QoL was estimated using the binary logistic model. The
      control variables were: age, BMI and number of co-morbidities. RESULTS: A
      significant difference was found between the two groups of self-assessment of UI
      impact for all KHQ domains. The MUI group showed worse scores than the SUI group
      for all domains, and OAB group, for limitation of physical and daily activities.
      There was a significant difference between the odds of the women in the SUI and
      MUI groups reporting worse effects of UI on QoL (OR=2.9; p=0.02). CONCLUSION: As
      reported at other reference services, MUI was the most commom type, and urinary
      loss had a moderate/major impact on QoL, affecting mainly role limitations
      domain. The adjusted analysis showed that women with MUI had almost three times
      greater odds of reporting worse impact on QoL than women with SUI.

PMID- 26312394
TI  - [Waiting time for the first colposcopic examination in women with abnormal
      Papanicolaou test].
AB  - PURPOSE: To evaluate the waiting times before obtaining the first colposcopic
      examination for women with abnormal Papanicolaou smears. METHODS: Retrospective
      cohort study conducted on patients who required a colposcopic examination to
      clarify an abnormal pap test, between 2002 January and 2008 August, in a
      metropolitan region of Brazil. The waiting times were defined as: Total Waiting
      Time (interval between the date of the pap test result and the date of the first
      colposcopic examination); Partial A Waiting Time (interval between the date of
      the pap test result and the date of referral); Partial B Waiting Time (interval
      between the date of referral and the date of the first colposcopic examination).
      Means, medians, relative and absolute frequencies were calculated. The Kruskal
      Wallis test and Pearson's chi-square test were used to determine statistical
      significance. RESULTS: A total of 1,544 women with mean of age of 34 years
      (SD=12.6 years) were analyzed. Most of them had access to colposcopic examination
      within 30 days (65.8%) or 60 days (92.8%) from referral. Mean Total Waiting Time,
      Partial A Waiting Time, and Partial B Waiting Time were 94.5 days (SD=96.8 days),
      67.8 days (SD=95.3 days) and 29.2 days (SD=35.1 days), respectively. CONCLUSION:
      A large part of the women studied had access to colposcopic examination within 60
      days after referral, but Total waiting time was long. Measures to reduce the
      waiting time for obtaining the first colposcopic examination can help to improve
      the quality of care in the context of cervical cancer control in the region, and
      ought to be addressed at the phase between the date of the pap test results and
      the date of referral to the teaching hospital.

PMID- 26312395
TI  - [Female breast cancer mortality in Brazil according to color].
AB  - PURPOSE: To describe the mortality of female breast cancer in Brazil according to
      color, in the years 2000 and 2010. METHODS: A descriptive study in which
      demographic data were obtained from the Brazilian Institute of Geography and
      Statistics (IBGE). The breast cancer death information in Brazil was collected
      from the Ministry of Health through the Mortality Information System (SIM). The
      crude mortality rates for female breast cancer were calculated according to color
      and age group, up to 49 years and >=50 years. The results obtained were
      distributed into five geographical regions of the country (North, Northeast,
      Midwest, South and Southeast). RESULTS: In Brazil, in women aged 50 or more, the
      highest crude mortality rates of breast cancer in 2000 were 62.6/100,000,
      46.0/100,000 and 29.7/100,000 among yellow, white and black women, respectively.
      In women under 50 years in 2000, the crude mortality ranged from 2.0/100,000
      among indigenous women to 6.8/100,000 among white women. After ten years, in
      women over 50 years, the crude mortality rate among yellow, white and black women
      was 21.5, 53.2 and 40.4 per 100,000, respectively. In the country's regions, the
      highest mortality rates of breast cancer were observed in white and black women
      from the South and Southeast. In the Northeast, mortality rates in black and
      brown women doubled in 2010. CONCLUSION: Breast cancer mortality rates show
      ethnic and geographical variations. However, it is not possible to exclude the
      possibility that large variations have occurred as a result of improvement in the
      quality of information on mortality in the country.

PMID- 26312396
TI  - Neurocognitive Outcome in Very Long-Term Survivors of Childhood Acute
      Lymphoblastic Leukemia After Treatment with Chemotherapy Only.
AB  - BACKGROUND: There is a concern regarding long-term cognitive late effects after
      treatment for acute lymphoblastic leukemia (ALL). The present study assessed
      neuropsychological function in very long-term childhood ALL survivors treated
      with chemotherapy only. We also investigated associations between neurocognitive
      performance and individual treatment load. PROCEDURE: One-hundred and twelve
      adult ALL survivors, diagnosed 1970-2002 before age 16 and treated with
      chemotherapy only, and 100 comparison peers underwent neuropsychological tests
      covering processing speed, executive functions, working memory, and verbal
      learning and memory. Individual cumulative doses of cytostatic agents were
      extracted from the medical records for each patient. RESULTS: Mean age at
      diagnosis for survivors was 6.3 years and mean follow-up time was 22.6 years.
      There was no difference in general intellectual ability between survivors and
      comparison peers. However, survivors performed significantly more poorly in the
      neurocognitive domains' processing speed (P = 0.003, Cohen's d 0.48), executive
      functions, and working memory (both P < 0.001, Cohen's d 0.81-0.95). Among
      survivors, the rates of poor neurocognitive performance (>1.5 SD below control
      mean) for processing speed was 22%, executive functions 31%, working memory 34%,
      and verbal learning and memory 16%. Comparing survivors with poor versus normal
      neurocognitive performance, we found no difference with respect to cumulative
      doses of any of the cytostatic agents, age at diagnosis, or gender. CONCLUSIONS:
      Very long-term survivors of childhood ALL treated exclusively with chemotherapy
      showed no impairment in general intellectual ability, but significantly poorer
      performance in several neurocognitive domains than comparison peers. However, no
      associations emerged between neurocognitive impairment and treatment burden.

PMID- 26312397
TI  - Comparison of extraction solvents and sorbents in the quick, easy, cheap,
      effective, rugged, and safe method for the determination of pesticide
      multiresidue in fruits by ultra high performance liquid chromatography with
      tandem mass spectrometry.
AB  - An improved analytical method was developed for the simultaneous quantification
      of several plant growth regulators and fungicides (carbendazim, pyrimethanil,
      metalaxyl, triadimefon, paclobutrazol, thiophanate, prochloraz, dimethomorph,
      difenoconazole, (4-chlorophenoxy)-acetic acid, (2,4-dichlorophenoxy)-acetic acid,
      thiadiazuron, forchlorfenuron and gibberellins) in fruits followed by ultra high
      performance liquid chromatography with tandem mass spectrometry. Samples were
      extracted and purified using a modified QuEChERS method. Different extraction
      solvents and sorbents in the QuEChERS method were compared. Optimum results were
      followed by the addition of 1% acetic acid in acetonitrile; C18 sorbent was added
      due to the acidic nature of several pesticides. The recoveries of the pesticides
      were in the range 73.7-118.4%, with relative standard deviations lower than
      16.63%. Limits of detection ranged from 0.1-1.0 MUg/kg. The method presented here
      is simple, rapid, sensitive and can be applied to large-scale monitoring programs
      to screen the presences of pesticides in fruits. 

PMID- 26312398
TI  - Helminth Parasites of Juvenile Green Turtles Chelonia mydas (Testudines:
      Cheloniidae) in Brazil.
AB  - The present study offers a parasitological analysis of juvenile individuals of
      the green turtle ( Chelonia mydas ) found on the Brazilian coast between 2004 and
      2011. Helminths were found in 90 out of 136 individuals (66.2%, CI = 57.7-74.0).
      In total, 29,411 helminths were collected, belonging to the families
      Brachycoeliidae, Cladorchiidae, Microscaphidiidae, Pronocephalidae, Rhytidodidae,
      and Spirorchiidae. Mean species richness was 4.74 (CI = 4.03-5.46), the mean
      intensity was 327 (CI = 223-489), and the mean abundance was 216 (CI = 146-339).
      This study also reports new geographical records for: Angiodictyum longum,
      Angiodictyum parallelum, Rameshwarotrema uterocrescens, Pyelosomum cochlear,
      Schizamphistomum scleroporum, Cymatocarpus solearis, and Neospirorchis sp. This
      is the first analysis of helminth composition in juveniles of green turtles. 

PMID- 26312399
TI  - Improvement of high-resolution fluorescence in situ hybridisation mapping on
      chromosomes of Brassica oleracea var. capitata.
AB  - The low resolution of chromosome-based Fluorescence in situ hybridisation (FISH)
      mapping is primarily due to the structure of the plant cell wall and cytoplasm
      and the compactness of regular chromosomes, which represent a significant
      obstacle to FISH. In order to improve spatial resolution and signal detection
      sensitivity, we provide a reproducible method to generate high-quality extended
      chromosomes that are ~13 times as long as their pachytene counterparts. We
      demonstrate that proteinase K used in this procedure is crucial for stretching
      pachytene chromosomes of Brassica oleracea in the context of a modified Carnoy's
      II fixative (6:1:3, ethanol:chloroform:acetic acid). The quality of super
      stretched chromosomes was assessed in several FISH experiments. FISH signals from
      both repetitive 5S rDNA and single-copy ARC1 on super-stretched chromosomes are
      brighter than those on other different types of chromosome due to enhanced
      accessibility to targets on stretched pachytene chromosomes. In conclusion, the
      resulting extended chromosomes are suitable for FISH mapping for repetitive DNA
      sequences and the localisation of a single-copy locus, and FISH performed on
      super-stretched chromosomes can achieve significantly higher sensitivity and
      spatial resolution than other chromosome-based FISH mapping techniques. 

PMID- 26312400
TI  - Clinical outcome in a Norwegian cohort of patients with chronic recurrent
      multifocal osteomyelitis.

PMID- 26312401
TI  - Magnesium as Novel Material for Active Plasmonics in the Visible Wavelength
      Range.
AB  - Investigating new materials plays an important role for advancing the field of
      nanoplasmonics. In this work, we fabricate nanodisks from magnesium and
      demonstrate tuning of their plasmon resonance throughout the whole visible
      wavelength range by changing the disk diameter. Furthermore, we employ a
      catalytic palladium cap layer to transform the metallic Mg particles into
      dielectric MgH2 particles when exposed to hydrogen gas. We prove that this
      transition can be reversed in the presence of oxygen. This yields plasmonic
      nanostructures with an extinction spectrum that can be repeatedly switched on or
      off or kept at any intermediate state, offering new perspectives for active
      plasmonic metamaterials. 

PMID- 26312402
TI  - Peripherally Inserted Central Catheter Use in Skilled Nursing Facilities: A Pilot
      Study.
AB  - OBJECTIVES: To describe patterns of use, care practices, and outcomes related to
      peripherally inserted central catheter (PICC) use in skilled nursing facilities
      (SNFs). DESIGN: Prospective cohort study. SETTING: Two community SNFs.
      PARTICIPANTS: Adult SNF residents with PICCs (N = 56). MEASUREMENTS: Information
      on indication for PICC use, device characteristics (e.g., lumens, gauge), and
      participant data (comorbidities, medications) were obtained from medical records.
      Care practices (e.g., frequency of flushing, dressing care) and problems related
      to PICCs were recorded. Major (central line-associated bloodstream infection,
      venous thromboembolism, catheter dislodgement) and minor (migration, dressing
      disruption, lumen occlusion, exit site infection) complications and process
      measures (flushing of PICC, assessment of necessity) were recorded. Bivariate
      analyses with t-tests, chi-square tests, or Fischer exact tests were used for
      continuous and categorical data. RESULTS: Participants were enrolled from two
      SNFs. The most common indication for PICC use was intravenous antibiotic
      delivery. The average PICC dwell time was 43 days, and most devices were single
      lumen PICCs. Major and minor complications were common and occurred in 11 (20%)
      and 18 (32%) participants, respectively. Occlusion (23%, n = 13), accidental
      dislodgement (12%, n = 7), and dressing disruption (11%, n = 6) were the
      commonest complications observed. Documentation regarding catheter care practices
      occurred in 41% of cases. CONCLUSION: Quality improvement efforts that seek to
      benchmark practice, identify gaps, and institute efforts to improve PICC care and
      practice in SNFs appear necessary.

PMID- 26312403
TI  - Circulating CD147 predicts mortality in advanced hepatocellular carcinoma.
AB  - BACKGROUND AND AIM: The glycoprotein CD147 has a role in tumor progression, is
      readily detectable in the circulation, and is abundantly expressed in
      hepatocellular carcinoma (HCC). Advanced HCC patients are a heterogeneous group
      with some individuals having dismal survival. The aim of this study was to
      examine circulating soluble CD147 levels as a prognostic marker in HCC patients.
      METHODS: CD147 was measured in 277 patients (110 HCC, 115 chronic liver disease,
      and 52 non-liver disease). Clinical data included etiology, tumor progression,
      Barcelona Clinic Liver Cancer (BCLC) stage, and treatment response. Patients with
      HCC were stratified into two groups based upon the 75th percentile of CD147
      levels (24 ng/mL). RESULTS: CD147 in HCC correlated inversely with poor survival
      (P = 0.031). Increased CD147 predicted poor survival in BCLC stages C and D (P =
      0.045), and CD147 levels >24 ng/mL predicted a significantly diminished 90-day
      and 180-day survival time (hazard ratio [HR] = 6.1; 95% confidence interval [CI]:
      2.1-63.2; P = 0.0045 and HR = 2.8; 95% CI: 1.2-12.6; P = 0.028, respectively). In
      BCLC stage C, CD147 predicted prognosis; levels >24 ng/mL were associated with a
      median survival of 1.5 months compared with 6.5 months with CD147 levels <=24
      ng/mL (P = 0.03). CD147 also identified patients with a poor prognosis
      independent from treatment frequency, modality, and tumor size. CONCLUSIONS:
      Circulating CD147 is an independent marker of survival in advanced HCC. CD147
      requires further evaluation as a potential new prognostic measure in HCC to
      identify patients with advanced disease who have a poor prognosis.

PMID- 26312404
TI  - Bryophyte communities as biomonitors of environmental factors in the Goujiang
      karst bauxite, southwestern China.
AB  - Bauxite mining on karst results in several ecological and environmental issues
      including heavy metal pollution, soil erosion and the destruction of vegetation.
      In turn, these may affect the distribution of plant communities and endanger
      human health. In general, bryophytes (mosses, liverworts and hornworts) are
      pioneer plants, lacking roots, vascular systems and well-developed cuticles. Due
      to their high sensitivity to the environment, they are often used to monitor air
      and soil pollution. A total of 25 bryophyte taxa from 19 genera and 9 families
      were recorded on Goujiang karst bauxite near the city of Zunyi in the Guizhou
      Province of southwestern China. Eleven principal bryophyte communities were
      identified, most of which consisted of only one species (monospecific
      assemblage), although the proportion of these single-species communities differed
      at the six locations. The levels of heavy metals also differed in soil from the
      six locations: iron, 8748.9-10,023MUg/g; zinc, 146.7-240.9MUg/g; copper, 24.6
      60.4MUg/g; and nickel, 35.6-95.1MUg/g. A canonical correspondence analysis (CCA)
      of the bryophyte communities and environmental variables revealed the effect of
      gradient (slope), altitude and heavy metals in the soil on the distribution of
      the principal bryophyte communities. More than 36% of bryophyte taxa identified
      reproduced asexually by gemmae, as gemmiferous bryophyte communities tolerate
      substrates with high levels of heavy metals more readily than non-gemmiferous
      communities do. The distribution of heavy metals in the soil is reflected in the
      distribution of the bryophyte communities. The distribution characteristics of
      the principal bryophyte communities and of the gemmiferous bryophyte communities
      are useful in monitoring heavy metal pollution in karst bauxite. 

PMID- 26312405
TI  - Mapping human health risks from exposure to trace metal contamination of drinking
      water sources in Pakistan.
AB  - The consumption of contaminated drinking water is one of the major causes of
      mortality and many severe diseases in developing countries. The principal
      drinking water sources in Pakistan, i.e. ground and surface water, are subject to
      geogenic and anthropogenic trace metal contamination. However, water quality
      monitoring activities have been limited to a few administrative areas and a
      nationwide human health risk assessment from trace metal exposure is lacking.
      Using geographically weighted regression (GWR) and eight relevant spatial
      predictors, we calculated nationwide human health risk maps by predicting the
      concentration of 10 trace metals in the drinking water sources of Pakistan and
      comparing them to guideline values. GWR incorporated local variations of trace
      metal concentrations into prediction models and hence mitigated effects of large
      distances between sampled districts due to data scarcity. Predicted
      concentrations mostly exhibited high accuracy and low uncertainty, and were in
      good agreement with observed concentrations. Concentrations for Central Pakistan
      were predicted with higher accuracy than for the North and South. A maximum 150
      200 fold exceedance of guideline values was observed for predicted cadmium
      concentrations in ground water and arsenic concentrations in surface water. In
      more than 53% (4 and 100% for the lower and upper boundaries of 95% confidence
      interval (CI)) of the total area of Pakistan, the drinking water was predicted to
      be at risk of contamination from arsenic, chromium, iron, nickel and lead. The
      area with elevated risks is inhabited by more than 74 million (8 and 172 million
      for the lower and upper boundaries of 95% CI) people. Although these predictions
      require further validation by field monitoring, the results can inform disease
      mitigation and water resources management regarding potential hot spots. 

PMID- 26312406
TI  - Redox processes in pore water of anoxic sediments with shallow gas.
AB  - The Ria de Vigo (NW Spain) has a high organic matter content and high rates of
      sedimentation. The microbial degradation of this organic matter has led to
      shallow gas accumulations of methane, currently distributed all along the ria.
      These peculiar characteristics favor the development of anoxic conditions that
      can determine the dynamics of iron and manganese. In order to study the role
      played by iron and manganese in the processes that take place in anoxic sediments
      with shallow gas, four gravity cores were retrieved in anoxic sediments of the
      Ria de Vigo in November 2012. Methane was present in two of them, below 90cm in
      the inner zone and below 200cm, in the outer zone. Pore water was collected and
      analyzed for vertical profiles of pH, sulfide, sulfate, iron and manganese
      concentrations. Sulfate concentrations decreased with depth but never reached the
      minimum detection limit. High sulfide concentrations were measured in all cores.
      The highest sulfide concentrations were found in the inner zone with methane and
      the lowest were in the outer zone without methane. Concentrations of iron and
      manganese reached maximum values in the upper layers of the sediment, decreasing
      with depth, except in the outer zone without gas, where iron and manganese
      concentration increased strongly toward the bottom of the sediment. In areas with
      shallow gas iron reduction, sulfate reduction and methane production processes
      coexist, showing that the traditional redox cascade is highly simplified and
      suggesting that iron may be involved in a cryptic sulfur cycle and in the
      oxidation of methane. 

PMID- 26312407
TI  - The role of anthropogenic and natural factors in shaping the geochemical
      evolution of groundwater in the Subei Lake basin, Ordos energy base, Northwestern
      China.
AB  - Groundwater resources are increasingly exploited for industrial and agricultural
      purposes in many arid regions globally, it is urgent to gain the impact of the
      enhanced anthropogenic pressure on the groundwater chemistry. The aim of this
      study was to acquire a comprehensive understanding of the evolution of
      groundwater chemistry and to identify the impact of natural and anthropogenic
      factors on the groundwater chemistry in the Subei Lake basin, Northwestern China.
      A total of 153 groundwater samples were collected and major ions were measured
      during the three campaigns (August and December 2013, May 2014). At present, the
      major hydrochemical facies in unconfined groundwater are Ca-Mg-HCO3, Ca-Na-HCO3,
      Na-Ca-HCO3, Na-HCO3, Ca-Mg-SO4 and Na-SO4-Cl types, while the main hydrochemical
      facies in confined groundwater are Ca-Mg-HCO3, Ca-Na-HCO3, Na-Ca-HCO3, Ca-HCO3
      and Na-HCO3 types. Relatively greater seasonal variation can be observed in the
      chemical constituents of confined groundwater than that of unconfined
      groundwater. Rock weathering predominates the evolution of groundwater chemistry
      in conjunction with the cation exchange, and the dissolution/precipitation of
      gypsum, halite, feldspar, calcite and dolomite are responsible for the chemical
      constituents of groundwater. Anthropogenic activities can be classified as: (1)
      groundwater overexploitation; (2) excessive application of fertilizers in
      agricultural areas. Due to intensive groundwater pumping, the accelerated
      groundwater mineralization resulted in the local changes in hydrochemical facies
      of unconfined groundwater, while the strong mixture, especially a large influx of
      downward leakage from the unconfined aquifer into the confined aquifer, played a
      vital role in the fundamental variation of hydrochemical facies in confined
      aquifer. The nitrate contamination is mainly controlled by the local
      hydrogeological settings coupled with the traditional flood irrigation. The
      deeper insight into geochemical evolution of groundwater obtained from this study
      can be beneficial to improving groundwater management for sustainable development
      in the rapidly industrialized areas. 

PMID- 26312408
TI  - Variability in ecosystem structure and functioning in a low order stream:
      Implications of land use and season.
AB  - Human activity can degrade the habitat quality for aquatic communities, which
      ultimately impacts the functions these communities provide. Disentangling the
      complex interaction between environmental and anthropogenic parameters as well as
      their alteration both along the stream channel, over the seasons, and finally
      their impact in the aquatic ecosystem represents a fundamental challenge for
      environmental scientists. Therefore, the present study investigates the
      implications of successive land uses (i.e., vineyard, urban area, highway and
      wastewater treatment plant (WWTP)) on structural and functional endpoints related
      to the ecosystem process of leaf litter breakdown during a winter and summer
      season in a five km stretch of a second-order stream in southern Germany. This
      sequence of the different land uses caused, among others, a downstream decline of
      the ecological status from "high" to "bad" judged based on the SPEARpesticides
      index together with significant shifts in the macroinvertebrate community
      composition, which coincided with substantial impairments (up to 100%) in the
      macroinvertebrate-mediated leaf decomposition. These effects, seem to be mainly
      driven by alterations in water quality rather than morphological modifications of
      the stream's habitat since the key shredder Gammarus was not in direct contact
      with the local habitat during in situ bioassays but showed similar response
      patterns than the other endpoints. While the relative effect size for most
      endpoints deviated considerably (sometimes above 2-fold) among seasons, the
      general response pattern pointed to reductions in energy supply for local and
      downstream communities. Although the present study focused on a single low-order
      stream with the main purpose of describing the impact of different land uses on
      various levels of biological organization, which limits the direct
      transferability and thus applicability of results to other stream ecosystems, the
      findings point to the need to develop adequate management strategies mitigating
      land use specific exposures during all seasons to protect ecosystem integrity. 

PMID- 26312409
TI  - Environmental fate of naproxen, carbamazepine and triclosan in wastewater,
      surface water and wastewater irrigated soil - Results of laboratory scale
      experiments.
AB  - Lab-scale photolysis, biodegradation and transport experiments were carried out
      for naproxen, carbamazepine and triclosan in soil, wastewater and surface water
      from a region where untreated wastewater is used for agricultural irrigation.
      Results showed that both photolysis and biodegradation occurred for the three
      emerging pollutants in the tested matrices as follows:
      triclosan>naproxen>carbamazepine. The highest photolysis rate for the three
      pollutants was obtained in experiments using surface water, while biodegradation
      rates were higher in wastewater and soil than in surface water. Carbamazepine
      showed to be recalcitrant to biodegradation both in soil and water; although
      photolysis occurred at a higher level than biodegradation, this compound was
      poorly degraded by natural processes. Transport experiments showed that naproxen
      was the most mobile compound through the first 30cm of the soil profile;
      conversely, the mobility of carbamazepine and triclosan through the soil was
      delayed. Biodegradation of target pollutants occurred within soil columns during
      transport experiments. Triclosan was not detected either in leachates or the soil
      in columns, suggesting its complete biodegradation. Data of these experiments can
      be used to develop more reliable fate-on-the-field and environmental risk
      assessment studies. 

PMID- 26312410
TI  - Antigenotoxic and Antimutagenic Activities of Probiotic Lactobacillus rhamnosus
      Vc against N-Methyl-N'-Nitro-N-Nitrosoguanidine.
AB  - The present study provides experimental evidence of in vivo reduction of
      genotoxic and mutagenic activities of potent carcinogen N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG) by the strain Lactobacillus rhamnosus Vc. In vitro
      studies revealed that coincubation of MNNG with viable cells of L. rhamnosus Vc
      resulted in the detoxification of the parent compound accompanied with reduction
      in genotoxicity (69%) and mutagenicity (61%) as evaluated by SOS-Chromotest and
      Ames test, respectively. Oral feeding of probiotic bacteria L. rhamnosus Vc
      (10(9) cfu) to Gallus gallus (chicks) for 30 days provided protection against
      MNNG-induced damage as evidenced from the significant decrease (P = 0.009) in
      glutathione S-transferase activity in the L. rhamnosus Vc+MNNG-treated chicks in
      comparison to the MNNG-treated chicks. Histopathology of colon and liver showed
      intact cells and mild inflammation in the L. rhamnosus Vc+MNNG-treated chicks,
      whereas heavy inflammation and degenerative changes were observed in MNNG-treated
      chicks. The results indicate that the probiotic L. rhamnosus Vc provided in vivo
      protection against MNNG-induced colon damage by detoxification of MNNG to less
      toxic metabolites.

PMID- 26312411
TI  - Comparative Study of the Effect of Glucosamine and Free Ammonium on 4
      Methylimidazole Formation.
AB  - The effect of glucosamine analogues (glucosamine and acetylglucosamine) and free
      ammonium on the formation of 4-methylimidazole (4-MeI) was investigated in the
      caramel model reaction systems. Methylglyoxal (MGO) was detected after
      derivatization by high-performance liquid chromatography with a diode array
      detector (HPLC-DAD). 4-MeI in the Maillard reaction was tested using a high
      performance cation exchange chromatography coupled with APCI-MS (HPCEC-MS). The
      levels of pyrazines tested by gas chromatography (GC) coupled with MS were
      applied to mark the condensation reaction between dicarbonyls and free ammonium.
      Results showed that the formation of 4-MeI and its precursor MGO was inhibited in
      glucosamine analogue model reaction systems. Besides, the results from pyrazines
      and brown intensity in glucosamine analogues model reaction systems indicated
      that glucosamine analogues mainly underwent the reaction of intra-intermolecular
      polymerization into melanoidins rather than the degradation reaction into MGO.
      Using glucosamine analogues to produce the caramel color with a low level of 4
      MeI was applicable. 

PMID- 26312412
TI  - Butyrate and Mucosal Inflammation: New Scientific Evidence Supports Clinical
      Observation.

PMID- 26312414
TI  - Exploiting Bacterial Pathways for BBB Crossing with PLGA Nanoparticles Modified
      with a Mutated Form of Diphtheria Toxin (CRM197): In Vivo Experiments.
AB  - Drugs can be targeted to the brain using polymeric nanoparticles (NPs) engineered
      on their surface with ligands able to allow crossing of the blood-brain barrier
      (BBB). This article aims to investigate the BBB crossing efficiency of polymeric
      poly lactide-co-glycolide (PLGA) NPs modified with a mutated form of diphtheria
      toxin (CRM197) in comparison with the results previously obtained using PLGA NPs
      modified with a glycopeptide (g7-NPs). Different kinds of NPs, covalently coupled
      PLGA with different fluorescent probes (DY405, rhodamine-B base and DY675) and
      different ligands (g7 and CRM197) were tested in vivo to assess their behavior
      and trafficking. The results highlighted the possibility to distinguish the
      different kinds of simultaneously administered NPs and to emphasize that CRM-197
      modified NPs and g7-NPs can cross the BBB at a similar extent. The analysis of
      BBB crossing and of the neuronal tropism of CRM197 modified NPs, along with their
      BBB crossing pathways were also developed. In vivo pharmacological studies
      performed on CRM197 engineered NPs, loaded with loperamide, underlined their
      ability as drug carriers to the CNS. 

PMID- 26312413
TI  - Current Concepts in Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis.
AB  - Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are
      chronic, cholestatic diseases of the liver with common clinical manifestations.
      Early diagnosis and treatment of PBC slows progression and decreases the need for
      transplant. However, one-third of patients will progress regardless of treatment.
      Bilirubin <1.0 and alkaline phosphatase <2.0 x the upper limit of normal at 1
      year after treatment appear to predict 10-year survival. Ursodeoxycholic acid
      (UDCA) is the recommended treatment for PBC, and recent studies with obeticholic
      acid showed promising results for UDCA non-responders. Unlike PBC, no therapy has
      been shown to alter the natural history of PSC. The recommended initial
      diagnostic test for PSC is magnetic resonance cholangiopancreatography, typically
      showing bile duct wall thickening, focal bile duct dilatation, and saccular
      dilatation of the intra- and/or extrahepatic bile ducts. Immunoglobulin 4
      associated cholangitis must be excluded when considering the diagnosis of PSC, to
      allow for proper treatment, and monitoring of disease progression. In addition to
      the lack of therapy, PSC is a pre-malignant condition and close surveillance is
      indicated. 

PMID- 26312415
TI  - Highly Porous (TiO2-SiO2-TeO2)/Al2O3/TiO2 Composite Nanostructures on Glass with
      Enhanced Photocatalysis Fabricated by Anodization and Sol-Gel Process.
AB  - Three-dimensional highly porous TiO2-4%SiO2-1%TeO2/Al2O3/TiO2 composite
      nanostructures (phi30-120 nm) directly fixed on glass substrates were fabricated
      by anodization of a superimposed Al/Ti layer sputter-deposited on glass and a sol
      gel process. The porous composite nanostructures exhibited enhanced
      photocatalytic performances in decomposing acetaldehyde gas under UV
      illumination, which can be mainly ascribed to the combination of their large
      surface areas (7750-14770 m(2)/m(2)), high porosities (34.2-45.6%), and
      transparency. Specially, the composite nanostructure with ~phi120 nm pores
      calcined at 500  degrees C showed the highest photocatalytic activity that is 6
      10 times higher than commercial P-25 TiO2 under the experimental conditions. 

PMID- 26312416
TI  - Photoinduced charge accumulation by metal ion-coupled electron transfer.
AB  - An oligotriarylamine (OTA) unit, a Ru(bpy)3(2+) photosensitizer moiety (Ru), and
      an anthraquinone (AQ) entity were combined to a molecular dyad (Ru-OTA) and a
      molecular triad (AQ-Ru-OTA). Pulsed laser excitation at 532 nm led to the
      formation of charge-separated states of the type Ru(-)-OTA(+) and AQ(-)-Ru-OTA(+)
      with lifetimes of <=10 ns and 2.4 MUs, respectively, in de-aerated CH3CN at 25 
      degrees C. Upon addition of Sc(OTf)3, very long-lived photoproducts were
      observed. Under steady-state irradiation conditions using a flux of (6.74 +/-
      0.21) * 10(15) photons per second at 450 nm, the formation of twofold oxidized
      oligotriarylamine (OTA(2+)) was detected in aerated CH3CN containing 0.02 M
      Sc(3+), as demonstrated unambiguously by comparison with UV-Vis absorption
      spectra obtained in the course of chemical oxidation with Cu(2+). Photodriven
      charge accumulation on the OTA unit of Ru-OTA and AQ-Ru-OTA is possible due to
      the lowering of the O2 reduction potential caused by the interaction of
      superoxide with the strong Lewis acid Sc(3+). The presence of the anthraquinone
      unit in AQ-Ru-OTA accelerates the rate-determining reaction step for charge
      accumulation by a factor of 10 compared to the Ru-OTA dyad. This is attributed to
      the formation of Sc(3+)-stabilized anthraquinone radical anion intermediates in
      the triad. Possible mechanistic pathways leading to charge accumulation are
      discussed. Photodriven charge accumulation is of key importance for solar fuels
      because their production will have to rely on multi-electron chemistry rather
      than single-electron reaction steps. Our study is the first to demonstrate that
      metal ion-coupled electron transfer (MCET) can be exploited to accumulate charges
      on a given molecular unit using visible light as an energy input. The approach of
      using a combination of intra- and intermolecular electron transfer reactions
      which are enabled by MCET is conceptually novel, and the fundamental insights
      gained from our study are relevant in the greater context of solar energy
      conversion. 

PMID- 26312417
TI  - Evaluation of protein extraction methods for enhanced proteomic analysis of
      tomato leaves and roots.
AB  - Proteomics is an outstanding area in science whose increasing application has
      advanced to distinct purposes. A crucial aspect to achieve a good proteome
      resolution is the establishment of a methodology that results in the best quality
      and wide range representation of total proteins. Another important aspect is that
      in many studies, limited amounts of tissue and total protein in the tissue to be
      studied are found, making difficult the analysis. In order to test different
      parameters, combinations using minimum amount of tissue with 4 protocols for
      protein extraction from tomato (Solanum lycopersicum L.) leaves and roots were
      evaluated with special attention to their capacity for removing interferents and
      achieving suitable resolution in bidimensional gel electrophoresis, as well as
      satisfactory protein yield. Evaluation of the extraction protocols revealed large
      protein yield differences obtained for each one. TCA/acetone was shown to be the
      most efficient protocol, which allowed detection of 211 spots for leaves and 336
      for roots using 500 ug of leaf protein and 800 ug of root protein per gel. 

PMID- 26312418
TI  - Disaggregases, molecular chaperones that resolubilize protein aggregates.
AB  - The process of folding is a seminal event in the life of a protein, as it is
      essential for proper protein function and therefore cell physiology.
      Inappropriate folding, or misfolding, can not only lead to loss of function, but
      also to the formation of protein aggregates, an insoluble association of
      polypeptides that harm cell physiology, either by themselves or in the process of
      formation. Several biological processes have evolved to prevent and eliminate the
      existence of non-functional and amyloidogenic aggregates, as they are associated
      with several human pathologies. Molecular chaperones and heat shock proteins are
      specialized in controlling the quality of the proteins in the cell, specifically
      by aiding proper folding, and dissolution and clearance of already formed protein
      aggregates. The latter is a function of disaggregases, mainly represented by the
      ClpB/Hsp104 subfamily of molecular chaperones, that are ubiquitous in all
      organisms but, surprisingly, have no orthologs in the cytosol of metazoan cells.
      This review aims to describe the characteristics of disaggregases and to discuss
      the function of yeast Hsp104, a disaggregase that is also involved in prion
      propagation and inheritance. 

PMID- 26312419
TI  - Mixed thermal convection: fundamental issues and analysis of the planar case.
AB  - This paper aims to renew interest on mixed thermal convection research and to
      emphasize three issues that arise from the present analysis: (i) a clear
      definition of the reference temperature in the Boussinesq approximation; (ii) a
      practical delimitation of the three convective modes, which are the forced
      convection (FC), mixed convection (MC) and natural (or free) convection (NC);
      (iii) and, finally, a uniform description of the set FC/MC/NC in the similarity
      framework. The planar case, for which analytical solutions are available, allows
      a detailed illustration of the answers here advanced to the above issues. 

PMID- 26312420
TI  - Prevalence and Fluconazole Susceptibility Profile of Candida spp. Clinical
      Isolates in a Brazilian Tertiary Hospital in Minas Gerais, Brazil.
AB  - Candidiasis has become an important concern for clinical practice, especially
      with the increasing incidence of immunocompromised patients. In this scenario,
      the development resistance to fluconazole presents a challenge for treating these
      opportunistic infections. The aim of this study was to evaluate some epidemiology
      features of Candida infections in a Brazilian University Hospital using data,
      previously unavailable. We observed that 44% of the 93 clinical isolates tested,
      belonged to Candida albicans species and 56% belonged to non-Candida albicans
      species (mainly Candida tropicalis and Candida glabrata). Most strains were
      isolated from urine samples where C. albicans was predominantly detected. 29
      strains presented a fluconazole resistance phenotype and of these, 22 were
      chemosensitised by FK506, a classical inhibitor of ABC transporters related to
      azoles resistance. These data suggest the probable role of efflux pumps in this
      resistance phenotype. Our study highlights the need for developing effective
      control measures for fungal infections, rational use of antifungal drugs and
      development of new molecules able to abrogate the active transport of
      antifungals.

PMID- 26312421
TI  - Structural Properties of the Brazilian Air Transportation Network.
AB  - The air transportation network in a country has a great impact on the local,
      national and global economy. In this paper, we analyze the air transportation
      network in Brazil with complex network features to better understand its
      characteristics. In our analysis, we built networks composed either by national
      or by international flights. We also consider the network when both types of
      flights are put together. Interesting conclusions emerge from our analysis. For
      instance, Viracopos Airport (Campinas City) is the most central and connected
      airport on the national flights network. Any operational problem in this airport
      separates the Brazilian national network into six distinct subnetworks. Moreover,
      the Brazilian air transportation network exhibits small world characteristics and
      national connections network follows a power law distribution. Therefore, our
      analysis sheds light on the current Brazilian air transportation infrastructure,
      bringing a novel understanding that may help face the recent fast growth in the
      usage of the Brazilian transport network. 

PMID- 26312422
TI  - Correlation between radiation dose and p53 protein expression levels in human
      lymphocytes.
AB  - The aim of this research was to evaluate the relationship between p53 protein
      levels and absorbed doses from in vitro irradiated human lymphocytes. For this,
      samples of blood from 23 donors were irradiated with 0.5; 1; 2; and 4 Gy from a
      Cobalt-60 source, and the percentages of lymphocytes expressing p53 were scored
      using Flow Cytometry. The subjects were divided into 3 groups, in accordance with
      the p53 levels expressed per radiation dose: low (Group I), high (Group II), and
      excessive levels (Group III). For all groups, the analyses showed that the p53
      expression levels increase with the absorbed dose. Particularly for groups I and
      II, the correlation between this protein expression and the dose follows the
      linear-quadratic model, such as for radioinduced chromosomal aberrations. In
      conclusion, our findings indicate possible applications of this approach in
      evaluating individual radiosensitivity prior to radiotherapeutical procedures as
      well as in medical surveillance of occupationally exposed workers. Furthermore,
      due to the rapidity of flow-cytometric analyses, the methodology here employed
      would play an important role in emergency responses to a large-scale radiation
      incident where many people may have been exposed. 

PMID- 26312423
TI  - Neutrotoxic effects of fructose administration in rat brain: implications for
      fructosemia.
AB  - Fructose accumulates in tissue and body fluids of patients affected by hereditary
      fructose intolerance (HFI), a disorder caused by the deficiency of aldolase B. We
      investigated the effect of acute fructose administration on the biochemical
      profile and on the activities of the Krebs cycle enzymes in the cerebral cortex
      of young rats. Rats received a subcutaneous injection of NaCl (0.9 %; control
      group) or fructose solution (5 MUmol/g; treated group). Twelve or 24 h after the
      administration, the animals were euthanized and the cerebral cortices were
      isolated. Peripheral blood (to obtain the serum) and cerebral spinal fluid (CSF)
      from the animals were also collected. It was observed that albumin levels were
      decreased and cholesterol levels were increased in CSF of animals 12 h after the
      administration of fructose. In addition, serum lactate levels were increased 12 h
      after the administration, as compared to control group. Furthermore, malate
      dehydrogenase activity was increased in cerebral cortex from treated group 24 h
      after the administration of this carbohydrate. Herein we demonstrate that
      fructose administration alters biochemical parameters in CSF and serum and
      bioenergetics parameters in the cerebral cortex. These findings indicate a
      possible role of fructose on brain alterations found in HFI patients. 

PMID- 26312424
TI  - Biochronostratigraphy and paleoenvironment analysis of Neogene deposits from the
      Pelotas Basin (well 2-TG-96-RS), Southernmost Brazil.
AB  - This paper presents the integration of micropaleontological (palynology and
      foraminifera) and isotopic (87Sr/86Sr) analysis of a selected interval from the
      well 2-TG-96-RS, drilled on the onshore portion of the Pelotas Basin, Rio Grande
      do Sul, Brazil. A total of eight samples of the section between 140.20 and 73.50
      m in depth was selected for palynological analysis, revealing diversified and
      abundant palynomorph associations. Species of spores, pollen grains and
      dinoflagellate cysts are the most common palynomorphs found. Planktic and benthic
      calcareous foraminifera were recovered from the lowest two levels of the section
      (140.20 and 134.30 m). Based on the stratigraphic range of the species of
      dinoflagellate cysts and sporomorphs, a span age from Late Miocene to Early
      Pliocene is assigned. The relative age obtained from the 87Sr/86Sr ratio in
      shells of calcareous foraminifers indicates a Late Miocene (Messinian)
      correspondence, corroborating the biostratigraphic positioning performed with
      palynomorphs. Paleoenvironmental interpretations based on the quantitative
      distribution of organic components (palynomorphs, phytoclasts and amorphous
      organic matter) throughout the section and on foraminiferal associations indicate
      a shallow marine depositional environment for the section. Two palynologicals
      intervals were recognized based on palynofacies analysis, related to middle to
      outer shelf (140.20 to 128.90 m) and inner shelf (115.75 to 73.50 m) conditions. 

PMID- 26312425
TI  - A new qualitative proof of a result on the real Jacobian conjecture.
AB  - Let F= (f, g) : R2 -> R2 be a polynomial map such that det DF(x) is different
      from zero for all x ? R2. We assume that the degrees of f and g are equal. We
      denote by f and G the homogeneous part of higher degree of f and g, respectively.
      In this note we provide a proof relied on qualitative theory of differential
      equations of the following result: If f and g do not have real linear factors in
      common, then F is injective.

PMID- 26312426
TI  - Alzheimer's Disease associated with Psychiatric Comorbidities.
AB  - Alzheimer's disease (AD) is the most common cause of dementia and has become a
      severe public health issue. It is estimated that globally, 35.6% of people have
      some form of dementia. This number is expected to double by 2030, and possibly
      even triple by 2050. The disease is associated with deficits in cognition/memory
      and a reduced ability in coping with everyday life. Moreover, patients can
      experience behavioral alterations such as mood swings, depression and
      hallucinations. Therefore, it is common to find the presence of neuropsychiatric
      comorbidities such as depression, schizophrenia and bipolar disorder during the
      course or development of AD. These disorders can become severe enough to
      interfere with the patients daily functioning, and can worsen the course of the
      disease. However, little is known about the causal relationship between
      psychiatric comorbidities and AD, or the reasons for the predisposition of some
      individuals to such disorders. Therefore, the purpose of this review is to
      clarify the causal relationship between depression, schizophrenia and bipolar
      disorder with AD. 

PMID- 26312427
TI  - Santonian dinocyst assemblages of the Santa Marta Formation, Antarctic Peninsula:
      Inferences for paleoenvironments and paleoecology.
AB  - To better understand the paleoenvironments of the lower-middle Santonian,
      dinocyst data were obtained from the Santa Marta Formation, Larsen Basin, James
      Ross Island, Antarctic Peninsula. This study provides the first available
      quantitative dinocyst data for the Santa Marta Formation, which should more
      clearly reflect detailed changes in paleoenvironments, as recorded by
      fluctuations in diversity and abundance. To record the Santonian dinocyst
      assemblages from the Larsen Basin, 30 samples from an outcrop of the Lachman
      Crags Member (LC section) were analyzed. These assemblages are dominated by
      peridiniacean dinocysts typical of the Isabelidinium flora. A lower-middle
      Santonian age was determined after the recognition of Odontochitina poriferaand
      Isabelidinium cretaceum zones. Cluster analysis based on quantitative data,
      yielded five dinocyst assemblages: Manumiella, Heterosphaeridium,
      Chlamydophorella, Isabelidinium and Odontochitina. Two Santonian blooms,
      Isabelidinium and Odontochitina,recognized in other regions were also recorded in
      the studied section. The stratigraphic distribution shows an alternation between
      the assemblages, distinguishing in the section six intervals. The high abundance
      of the Manumiella assemblage at the uppermost interval of the section represents
      the shallower setting, whereas the high abundance of Odontochitina at the middle
      part of the section represents the deepest setting. 

PMID- 26312428
TI  - Abdominal macrochaetae of female Hylesia oratex Dyar, 1913 (Insecta: Lepidoptera:
      Saturniidae): external morphology and medical significance.
AB  - The representatives of the genus Hylesia Hubner, [1820] are significant among the
      medically important Lepidoptera. Adult females use abdominal setae to wrap and
      protect the eggs that remain for months in nature. These setae, in contact with
      human skin, may cause allergic reactions including swelling, itching and local
      erythema, known as lepidopterism. The morphology of the abdominal scales and
      setae from the female H. oratex Dyar, 1913 is herein described and aspects
      related to their medical significance are discussed. Portions of each abdominal
      segment were examined through a scanning electron microscope. Two types of scales
      without medical importance, and two types of setae with medical importance,
      classified as "true setae" and "modified setae" were found. The true setae, which
      are slightly fusiform and have radially arranged lateral projections, are
      responsible for the allergic reactions caused by skin penetration. The modified
      setae, which are larger, curved, with the median enlarged and serrated margins,
      can be responsible for the release of chemical substances. This information
      provides a better understanding of the structure of the urticating setae, which
      are responsible for lepidopterism outbreaks in humans, and contributes towards
      the identification of the moth species involved. 

PMID- 26312429
TI  - Zircon ages delimit the provenance of a sand extrudite from the Botucatu
      Formation in the Parana volcanic province, Irai, Brazil.
AB  - Ion microprobe age determinations of 102 detrital zircon crystals from a sand
      extrudite, Cretaceous Parana volcanic province, set limits on the origin of the
      numerous sand layers present in this major flood basalt province. The zircon U-Pb
      ages reflect four main orogenic cycles: Mesoproterozoic (1155-962 Ma), latest
      Proterozoic-early Cambrian (808-500 Ma) and two Palaeozoic (Ordovician- 480 to
      450 Ma, and Permian to Lower Triassic- 296 to 250 Ma). Two additional small
      concentrations are present in the Neoarchean (2.8 to 2.6 Ga) and Paleoproterozoic
      (2.0 to 1.7 Ga). Zircon age peaks closely match the several pulses of igneous
      activity in the Precambrian Brazilian Shield and active orogeny in Argentina. A
      main delimitation of the origin of the sand is the absence of zircon ages from
      the underlying Cretaceous basalts, thus supporting an injectite origin of the
      sand as an extrudite that emanated from the paleoerg that constitutes the
      Botucatu Formation.

PMID- 26312430
TI  - Effects of primaquine and chloroquine on oxidative stress parameters in rats.
AB  - Primaquine and chloroquine are used for the treatment of malaria; evidence from
      the literature suggests that these drugs may induce oxidative stress. In this
      study we investigated the effects of primaquine and chloroquine on oxidative
      damage and DNA damage in brain, liver and kidney of rats after 7, 14 and 21 days
      of administration. Our results demonstrated that primaquine causes DNA damage in
      brain after 7, 14 and 21 days, and in liver after 7 and 14 days. Moreover,
      primaquine increases TBARS levels in the kidney and protein carbonyls in the
      brain after 14 days, and decreases protein carbonyls in the liver after 7 days.
      Whereas chloroquine causes DNA damage in the kidney after 7 and 14 days, and in
      the liver after 14 and 21 days, increases TBARS levels in the kidney after 7
      days, and decreases TBARS levels in the brain after 21 days. Moreover, decreases
      protein carbonyls in the liver after 7 and 14 days, and in the brain after 7 and
      21 days. However, chloroquine treatment for 14 days increases protein carbonyls
      in the brain and kidney. In conclusion, these results showed that prolonged
      treatment with antimalarial may adversely affect the DNA. 

PMID- 26312431
TI  - The re-emergency and persistence of vaccine preventable diseases.
AB  - The introduction of vaccination worldwide dramatically reduced the incidence of
      pathogenic bacterial and viral diseases. Despite the highly successful
      vaccination strategies, the number of cases among vaccine preventable diseases
      has increased in the last decade and several of those diseases are still endemic
      in different countries. Here we discuss some epidemiological aspects and possible
      arguments that may explain why ancient diseases such as, measles, polio,
      pertussis, diphtheria and tuberculosis are still with us. 

PMID- 26312432
TI  - Functional inhibition of PAR2 alleviates allergen-induced airway
      hyperresponsiveness and inflammation.
AB  - BACKGROUND: Proteinase-activated receptor 2 (PAR2 ) is a G protein-coupled
      receptor activated by trypsin-like serine proteinases. PAR2 activation has been
      associated with inflammation including allergic airway inflammation. We have also
      shown that PAR2 activation in the airways leads to allergic sensitization. The
      exact contribution of PAR2 in the development of eosinophilic inflammation and
      airway hyperresponsiveness (AHR) in sensitized individuals is not clear.
      OBJECTIVE: To investigate whether functional inhibition of PAR2 during allergen
      challenge of allergic mice would inhibit allergen-induced AHR and inflammation in
      mouse models of asthma. METHODS: Mice were sensitized and challenged with
      ovalbumin (OVA) or cockroach extract (CE). To investigate the role of PAR2 in the
      development of AHR and airway inflammation, we administered blocking anti-PAR2
      antibodies, or a cell permeable peptide inhibitor of PAR2 signalling, pepducin,
      i.n. before allergen challenges and then assessed AHR and airway inflammation.
      RESULTS: Administration of anti-PAR2 antibodies significantly inhibited OVA- and
      CE-induced AHR and airway inflammation. In particular, two anti-PAR2 antibodies,
      the monoclonal SAM-11 and polyclonal B5, inhibited AHR, airway eosinophilia, the
      increase of cytokines in the lung tissue and antigen-specific T cell
      proliferation, but had no effect on antigen-specific IgG and IgE levels. Pepducin
      was also effective in inhibiting AHR and airway inflammation in an OVA model of
      allergic airway inflammation. CONCLUSIONS AND CLINICAL RELEVANCE: Functional
      blockade of PAR2 in the airways during allergen challenge improves allergen
      induced AHR and inflammation in mice. Therefore, topical PAR2 blockade in the
      airways, through anti-PAR2 antibodies or molecules that interrupt PAR2
      signalling, has the potential to be used as a therapeutic option in allergic
      asthma.

PMID- 26312433
TI  - Design, synthesis and evaluation of thiohydantoin derivatives as potent
      topoisomerase I (Top1) inhibitors with anticancer activity.
AB  - DNA topoisomerase I is a potential chemotherapeutic target. Here, we designed and
      synthesized a library comprising of hydantoin and thiohydantoin derivatives and
      tested them against human and Leishmania Top1. One of the thiohydantoin compounds
      with substituted thiophenyl as the central moiety (compound 15) exhibited potent
      inhibition of human Top1 (HTop1) through stabilization of Top1-DNA cleavage
      complexes and showed selective anticancer activity against human cervical
      carcinoma (HeLa) and breast carcinoma (MCF-7) cell lines. Molecular modeling
      studies with HTop1 rationalized the inhibitory mechanism of compound 15.

PMID- 26312434
TI  - Recent developments regarding the use of thieno[2,3-d]pyrimidin-4-one derivatives
      in medicinal chemistry, with a focus on their synthesis and anticancer
      properties.
AB  - It is generally understood that the antitumor properties of synthetic
      heterocyclic compounds are among the most powerful properties that can be made
      use in medicinal chemistry. More specifically, their substantial cytotoxic
      effects against different types of human tumor cells, in addition to their roles
      as enzymes or receptors for various kinase inhibitors, make them critically
      important. In recent years, thieno[2,3-d]pyrimidin-4-one derivatives (TPs), which
      are analogs of quinazoline alkaloids, have frequently attracted the interest of
      medicinal chemistry researchers due to their promising anticancer properties. The
      present study is a review of the latest advances (i.e., since 2006) in TP
      derivative-related research, with a focus on how such derivatives are synthesized
      and on their anticancer activities. 

PMID- 26312435
TI  - Use of the Teres Major Muscle in Chimeric Subscapular System Free Flaps for Head
      and Neck Reconstruction.
AB  - IMPORTANCE: We present what we believe to be the first case series in which the
      teres major muscle is used as a free flap in head and neck reconstruction.
      OBJECTIVES: To describe our experience with the teres major muscle in free flap
      reconstruction of head and neck defects and to identify advantages of this
      approach. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review was performed
      at 2 tertiary care centers between February 1, 2007, and June 30, 2012. Data
      analysis was conducted from July 31, 2014, through December 1, 2014.
      INTERVENTION: Teres major muscle free flap for use in head and neck
      reconstruction. MAIN OUTCOMES AND MEASURES: Indications for use, complications,
      and outcomes including donor site morbidity. RESULTS: The teres major free flap
      was used in 11 patients as a component of chimeric subscapular system free flaps
      for a variety of complex head and neck defects. The teres major muscle was used
      to fill soft-tissue defects of the neck, face, and nasal cavity; it provided
      substantial soft-tissue volume but was less bulky than the latissimus dorsi
      muscle. The teres major muscle was also used to provide protection for vascular
      anastomoses and/or great vessels and to enhance soft-tissue coverage of the
      mandibular reconstruction plate. In addition, the muscle was selected as a
      substrate for skin grafting where inadequate neck skin remained. Flap survival
      occurred in 10 of 11 flaps (91%). Two flaps (18%) demonstrated venous congestion
      that was managed successfully. Two patients (18%) developed minor recipient-site
      complications (submental fistula and infection with recurrent wound dehiscence
      and plate exposure). All donor sites healed well, with chronic, mild shoulder
      pain noted in 2 patients (18%) and no postoperative seromas observed in any
      patient. CONCLUSIONS AND RELEVANCE: Addition of the teres major muscle to a
      subscapular system free flap is an option for reconstruction of a variety of
      complex head and neck defects, particularly when a moderate amount of soft tissue
      is required. In select cases, the teres major muscle may have advantages over the
      latissimus dorsi muscle.

PMID- 26312436
TI  - Triggerable Degradation of Polyurethanes for Tissue Engineering Applications.
AB  - Tissue engineered and bioactive scaffolds with different degradation rates are
      required for the regeneration of diverse tissues/organs. To optimize tissue
      regeneration in different tissues, it is desirable that the degradation rate of
      scaffolds can be manipulated to comply with various stages of tissue
      regeneration. Unfortunately, the degradation of most degradable polymers relies
      solely on passive controlled degradation mechanisms. To overcome this challenge,
      we report a new family of reduction-sensitive biodegradable elastomeric
      polyurethanes containing various amounts of disulfide bonds (PU-SS), in which
      degradation can be initiated and accelerated with the supplement of a biological
      product: antioxidant-glutathione (GSH). The polyurethanes can be processed into
      films and electrospun fibrous scaffolds. Synthesized materials exhibited robust
      mechanical properties and high elasticity. Accelerated degradation of the
      materials was observed in the presence of GSH, and the rate of such degradation
      depends on the amount of disulfide present in the polymer backbone. The polymers
      and their degradation products exhibited no apparent cell toxicity while the
      electrospun scaffolds supported fibroblast growth in vitro. The in vivo
      subcutaneous implantation model showed that the polymers prompt minimal
      inflammatory responses, and as anticipated, the polymer with the higher disulfide
      bond amount had faster degradation in vivo. This new family of polyurethanes
      offers tremendous potential for directed scaffold degradation to promote maximal
      tissue regeneration. 

PMID- 26312437
TI  - Why does moral reasoning not improve in medical students?

PMID- 26312438
TI  - An organocatalytic strategy for the stereoselective synthesis of C-galactosides
      with fluorine at the pseudoanomeric carbon.
AB  - The alpha-fluorination of alpha- and beta-C-ethanals of galactose using Jorgensen
      catalysts and NFSI was investigated. The crude reaction products were transformed
      to their primary alcohol or methylenated derivatives, which are versatile
      precursors to biologically interesting fluorinated glycomimetics. The alpha-C
      glycoside substrate gave moderate to high yields of fluorinated alpha-C
      glycosides with minor amounts of beta-C-glycoside analogues. The reactions on the
      beta-C-glycoside were lower yielding but gave exclusively fluorinated beta-C
      glycosides. For both alpha- and beta-C-glycoside substrates (R) and (S) catalyst
      showed complementary stereoselectivity. The preparation of difluorinated
      materials required the use of racemic catalyst as enantiomerically pure catalyst
      gave intractable mixtures of products. These results are in line with the results
      for simple achiral aldehydes, and suggest that stereochemistry in the reactions
      of these chiral, highly substituted, carbohydrate-derived aldehydes are
      controlled primarily by the chirality in the catalyst. 

PMID- 26312439
TI  - Acute skin reaction suggestive of pembrolizumab-induced radiosensitization.
AB  - The combination of localized radiotherapy and immune checkpoint inhibitors
      represents a promising therapeutic strategy for various cancers, including
      metastatic melanoma. Radiation therapy may enhance tumor antigen presentation and
      cytokine release, which may optimize the systemic antitumor immune response
      induced by these immunotherapeutic antibodies, with a potential delayed abscopal
      effect. However, clinical experience of using immune checkpoint inhibitors with
      concurrent radiotherapy remains scarce. We report here for the first time a case
      suggestive of acute skin radiosensitization induced by pembrolizumab, with a
      suggestive time relationship between the completion of ionizing radiation, drug
      administration, and rapid onset of the skin reaction. This suggests that
      radiation therapy may also interact rapidly with anti-programmed-death 1
      antibodies. Therefore, caution should be exercised when prescribing this
      combination therapy in advanced cancers. 

PMID- 26312440
TI  - The effects of carbamazepine on macroinvertebrate species: Comparing bivalves and
      polychaetes biochemical responses.
AB  - In the present study, the bivalve Scrobicularia plana and the polychaete Diopatra
      neapolitana were exposed to an increasing carbamazepine (CBZ) concentration
      gradient. Both species are among the most widely used bioindicators, and CBZ is
      one of the most commonly found drugs in the aquatic environment. After a chronic
      exposure (28 days), the results obtained revealed that CBZ induced biochemical
      alterations in both species. Our findings demonstrated that S. plana and D.
      neapolitana reduced the CBZ accumulation rate at higher CBZ concentrations,
      probably due to their capacity to decrease their feeding rates at stressful
      conditions. Nevertheless, this defence mechanism was not enough to prevent both
      species from oxidative stress. In fact, S. plana and D. neapolitana were not able
      to efficiently activate their antioxidant defence mechanisms which resulted in
      the increase of lipid peroxidation, especially at the highest CBZ concentrations.
      Comparing both species, it seems that S. plana was the most sensitive species
      since stronger biochemical alterations were observed in this species.

PMID- 26312441
TI  - Well-Defined Noble Metal Single Sites in Zeolites as an Alternative to Catalysis
      by Insoluble Metal Salts.
AB  - Insoluble precious metal chlorides in polymeric form (i.e., PtCl2, PdCl2, AuCl,
      RhCl3) are commonly used as catalysts for a plethora of organic reactions in
      solution. Here we show that only the minor soluble fraction of these precious
      metal chlorides (typically 5-30%) is catalytically active for the hydroamination,
      hydroalkoxylation, hydrosilylation, and cycloisomerization of alkynes and
      alkenes, and that the resting insoluble metal is catalytically useless. To
      circumvent this waste of precious metal and follow a rational design, we generate
      here well-dispersed Pt(II) and Pd(II) single sites on zeolite Y, with an
      exquisite control of the Lewis acidity, to catalyze different hydroaddition
      reactions to alkynes and alkenes with up to 10(4) catalytic cycles (at least 2
      orders of magnitude superior to precious metal chlorides) and with high isolated
      yields (82-99%, >15 examples). 

PMID- 26312442
TI  - Leishmaniasis: treatment updates and clinical practice guidelines review.
AB  - PURPOSE OF REVIEW: This review summarizes recent important and interesting
      articles investigating the challenging treatment of the parasitic infection,
      leishmaniasis. In addition, it compares and contrasts leishmaniasis clinical
      practice treatment guidelines. RECENT FINDINGS: Studies show that, in contrast to
      experience in India, visceral leishmaniasis in East Africa requires higher doses
      of liposomal amphotericin for effective treatment results and that pentavalent
      antimonial drugs remain efficacious. A retrospective study of visceral
      leishmaniasis in organ transplant patients suggests that there may be a role for
      secondary prophylaxis after treatment akin to HIV coinfection recommendations.
      The pros and cons of oral therapy with miltefosine, which cuts across
      leishmaniasis syndromes in its spectrum, are discussed. Cutaneous leishmaniasis
      clinical practice guidelines vary, although the recent European guidelines favor
      species-directed therapy. SUMMARY: Leishmaniasis remains a neglected tropical
      disease, with a need for additional clinical trials with better design and
      reported endpoints to lead evidence-based treatment recommendations--especially
      in cutaneous leishmaniasis and leishmaniasis in the immunocompromised host.

PMID- 26312444
TI  - The Influence of Absolute and Comparative Risk Perceptions on Cervical Cancer
      Screening and the Mediating Role of Cancer Worry.
AB  - This research investigates the interrelationships between cancer risk perceptions
      (absolute and comparative risk perceptions), cancer worry, and cervical cancer
      screening. Using a nationally representative survey data set (N = 2,304) from the
      2012 Health Information National Trends Survey Circle 1, we found that although
      neither absolute risk perceptions nor comparative risk perceptions exerted a
      direct impact on women's compliance with the cervical cancer screening
      recommendation (i.e., that women ages 21 to 65 obtain Pap smear every 3 years;
      U.S. Preventive Services Task Force, 2012 ), both types of risk perceptions had
      an indirect effect on cervical cancer screening through the mediation of cancer
      worry. These results suggest a primal role of affect in health decision making.
      Implications of the findings for cancer risk communication are discussed.

PMID- 26312445
TI  - Local infiltration analgesia is not improved by postoperative intra-articular
      bolus injections for pain after total hip arthroplasty.
AB  - BACKGROUND AND PURPOSE: The effect of postoperative intra-articular bolus
      injections after total hip arthroplasty (THA) remains unclear. We tested the
      hypothesis that intra-articular bolus injections administered every 6 hours after
      surgery during the first 24 hours would significantly improve analgesia after
      THA. PATIENTS AND METHODS: 80 patients undergoing THA received high-volume local
      infiltration analgesia (LIA; 200 mg ropivacaine and 30 mg ketorolac) followed by
      4 intra-articular injections with either ropivacaine (100 mg) and ketorolac (15
      mg) (the treatment group) or saline (the control group). The intra-articular
      injections were combined with 4 intravenous injections of either saline
      (treatment group) or 15 mg ketorolac (control group). All patients received
      morphine as patient-controlled analgesia (PCA). The primary outcome was
      consumption of intravenous morphine PCA and secondary outcomes were consumption
      of oral morphine, pain intensity, side effects, readiness for hospital discharge,
      length of hospital stay, and postoperative consumption of analgesics at 3, 6, and
      12 weeks after surgery. RESULTS: There were no statistically significant
      differences between the 2 groups regarding postoperative consumption of
      intravenous morphine PCA. Postoperative pain scores during walking were higher in
      the treatment group from 24-72 hours after surgery, but other pain scores were
      similar between groups. Time to readiness for hospital discharge was longer in
      the treatment group. Other secondary outcomes were similar between groups.
      INTERPRETATION: Postoperative intra-articular bolus injections of ropivacaine and
      ketorolac cannot be recommended as analgesic method after THA.

PMID- 26312446
TI  - Should medical students be taught ultrasonography?

PMID- 26312447
TI  - Vitreous in Age-Related Macular Degeneration Therapy--The Medium Is the Message.

PMID- 26312448
TI  - Illumination Techniques for Complex Pediatric Anterior Retinal Detachment and
      Associated Retrolental Plaque.

PMID- 26312449
TI  - The Tutoplast Approach: Preventing Conjunctival Erosion After Retisert
      Implantation.

PMID- 26312450
TI  - Correspondence.

PMID- 26312451
TI  - Reply: To PMID 25748280.

PMID- 26312452
TI  - Correspondence.

PMID- 26312453
TI  - Reply: To PMID 25545482.

PMID- 26312454
TI  - Byssogenesis in the juvenile pink heelsplitter mussel, Potamilus alatus
      (Bivalvia: Unionidae).
AB  - The North American pink heelsplitter (Potamilus alatus) differs from most
      freshwater mussels in China by the ability to secrete an ephemeral byssus during
      its juvenile stage. In the present study, light microscopy, scanning electron
      microscopy (SEM), and transmission electron microscopy (TEM) were used to
      investigate this ephemeral byssal structure, and amino acid composition was
      analyzed and compared with that of other species. The results revealed that the
      byssus consists of a long byssal thread and a few adhesive plaques which are
      randomly set up along the thread and assembled by petioles. There is a thin but
      distinctive cuticle with a continuous homogeneous matrix surrounding the byssal
      thread. Structural variation occurred when the byssal thread was differentially
      stretched. Four-stranded helical primary fasciculi, which form a stable rope-like
      structure, become evident after removal of the cuticle. The primary fasciculi
      consist of bundles of hundreds of parallel secondary fasciculi, each measuring
      about 5 MUm in diameter. All evidence indicates that the byssus of the pink
      heelsplitter has a significantly different macrostructure and microstructure than
      the permanent byssus of the marine mussel Mytilus. Byssogenesis ceases when
      juveniles exceed 30 mm in length, although it varies greatly even among juveniles
      of similar size. Byssus formation is influenced by substrate type. The unique
      characteristics of the byssus have important advantages for survival, transition,
      and aggregation during the early life history. This study not only provides first
      insight into the structure of the ephemeral byssus and its relationship to
      freshwater mussel development and growth, but also suggests possibilities for the
      synthesis of novel biopolymer materials particularly useful in freshwater
      ecosystems.

PMID- 26312456
TI  - A new member of troglobitic Carychiidae, Koreozospeum nodongense gen. et sp. n.
      (Gastropoda, Eupulmonata, Ellobioidea) is described from Korea.
AB  - A new genus of troglobitic Carychiidae Jeffreys, 1830 is designated from Nodong
      Cave, North Chungcheong Province, Danyang, South Korea. This remarkable find
      represents a great range extension and thus, a highly distant distribution of
      troglobitic Carychiidae in Asia. The Zospeum-like, carychiid snails were recently
      included, without a formal description, in records documenting Korean
      malacofauna. The present paper describes Koreozospeum Jochum & Prozorova, gen. n.
      and illustrates the type species, Koreozospeum nodongense Lee, Prozorova &
      Jochum, sp. n. using novel Nano-CT images, including a video, internal shell
      morphology, SEM and SEM-EDX elemental compositional analysis of the shell. 

PMID- 26312455
TI  - Towards a new conceptualization of depression in older adult cancer patients: a
      review of the literature.
AB  - OBJECTIVES: Identifying depression in older adults with cancer presents a set of
      unique challenges, as it combines the confounding influences of cancer and its
      treatment with the developmental changes associated with aging. This paper
      reviews the phenomenology of depression in older adults, and individuals
      diagnosed with cancer. METHOD: PsychInfo, PubMed, Web of Science, and Google
      Scholar databases were searched for English-language studies addressing the
      phenomenology, symptoms, or assessment of depression in older adults and those
      with cancer. RESULTS: The Diagnostic and Statistical Manual for Mental Disorders
      (DSM) criteria that appear to be relevant to both older adults and cancer
      patients are anhedonia, concentration difficulties, sleep disturbances,
      psychomotor retardation/agitation, and loss of energy. Possible alternative
      criteria that may be important considerations included constructs such as loss of
      purpose, loneliness, and irritability in older adults. Among cancer patients,
      tearfulness, social withdrawal, and not participating in treatment despite
      ability to do so were identified as potentially important symptoms. CONCLUSIONS:
      Current DSM criteria may not adequately assess depression in older cancer
      patients and alternative criteria may be important to inform the understanding
      and identification of depression in this population. Enhancing diagnostic
      accuracy of depression is important as both the over-diagnosis and under
      diagnosis is accompanied with significant costs. Thus, continued research
      exploring the phenomenology and identifying effective indicators of depression in
      older cancer patients is needed.

PMID- 26312457
TI  - Liver regeneration following experimental major hepatectomy with
      choledochojejunostomy.
AB  - BACKGROUND: Surgical treatment for perihilar cholangiocarcinoma frequently
      involves hepatectomy and extrahepatic bile duct resection with a
      choledochojejunostomy (CJ). Cholangitis owing to bilioenteric anastomosis is a
      common complication. The impact of CJ or regurgitating cholangitis on the liver
      regeneration process after major hepatectomy is unknown. METHODS: Rats underwent
      70 per cent hepatectomy (Hx group) or hepatectomy with CJ (Hx + CJ group). The
      intrahepatic inflammatory response, hepatic regeneration rate, and expression of
      regeneration-associated genes in the liver and blood were compared between these
      two groups. RESULTS: Levels of hepatobiliary markers in the blood were
      significantly higher 4 and 7 days after operation in the Hx + CJ group than the
      Hx group. Intrahepatic expression of inflammation-associated genes, such as
      interleukin 6 and tumour necrosis factor alpha, was also significantly higher in
      the Hx + CJ group on days 4 and 7. A progressive periportal inflammatory response
      was identified in the Hx + CJ group by histological examination. The hepatic
      regeneration rate was significantly lower in the Hx + CJ group than in the Hx
      group on day 2 (mean(s.d.) 14.2(6.3) versus 21.4(2.6) per cent; P = 0.013) and
      day 4 (32.4(5.3) versus 41.3(4.4) per cent; P = 0.004). Gene expression levels of
      hepatic regeneration-promoting factors such as hepatocyte growth factor were
      significantly lower in the Hx + CJ group than the Hx group on day 1. CONCLUSION:
      CJ perturbs early liver regeneration after hepatectomy. An excessive inflammatory
      response in the liver and suppression of liver regeneration-associated factors
      may play a role. Surgical relevance Patients with perihilar cholangiocarcinoma
      may need major hepatectomy with extrahepatic bile duct resection and
      choledochojejunostomy. This carries a substantial risk of postoperative
      complications including liver failure. A rat model of partial hepatectomy with
      choledochojejunostomy was established. The molecular mechanisms underlying liver
      regeneration, and perturbation of this process by duodenobiliary reflux via the
      choledochojejunostomy, are described. The results give insight into the
      pathophysiological events following major hepatectomy with extrahepatic bile duct
      resection and choledochojejunostomy. This may help to develop a treatment
      strategy to reduce postoperative liver failure.

PMID- 26312458
TI  - Short Channel Field-Effect-Transistors with Inkjet-Printed Semiconducting Carbon
      Nanotubes.
AB  - Short channel field-effect-transistors with inkjet-printed semiconducting carbon
      nanotubes are fabricated using a novel strategy to minimize material consumption,
      confining the inkjet droplet into the active channel area. This fabrication
      approach is compatible with roll-to-roll processing and enables the formation of
      high-performance short channel device arrays based on inkjet printing. 

PMID- 26312459
TI  - Operative vs. nonoperative treatment for comminuted proximal humeral fractures in
      elderly patients: a current meta-analysis.
AB  - OBJECTIVE: The aim of this study was to compare the effect of operative vs.
      nonoperative treatment for comminuted proximal humeral fractures in elderly
      patients regarding clinical results, complications, and additional surgeries.
      METHODS: Six electronic databases (Medline, Embase, Clinical, Ovid, Biosos, and
      Cochrane Central Register of Controlled Trials) were systematically searched to
      identify randomized controlled trials (RCTs). Eligible RCTs published between
      1960-2012 comparing operative vs. nonoperative treatment of comminuted proximal
      humeral fractures were included. Trial quality was assessed using the modified
      Jadad scale. Data from included studies were pooled with the use of fixed-effects
      and random-effects models with mean difference and risk ratios for continuous and
      dichotomous variables, respectively. Sensitivity analysis was performed to
      account for bias in patient selection. RESULTS: Six studies matched the selection
      criteria, reporting on 287 patients. One hundred fourty-four patients (50.17%)
      were managed nonoperatively, 20 patients (6.97%) underwent tension band fixation,
      55 patients (19.16%) were treated with locked plate, and 68 patients (23.69%)
      underwent hemiarthroplasty. Mean follow-up ranged from 12-50 months. Results
      showed no significant difference in post-treatment Constant scores and DASH
      scores, but conservative treatment showed superior results compared to operative
      treatment using EQ-5DTM. Compared with operative treatment, nonoperative
      treatment led to significantly fewer complications and additional surgeries.
      Findings from subgroup analyses remained consistent with these outcomes when
      compared to nonoperative treatment with tension band fixation, locked plate
      fixation, and hemiarthroplasty. CONCLUSION: Compared with operative treatment for
      closed comminuted proximal humeral fractures in elderly patients, conservative
      treatment can effectively reduce the risk of additional surgeries and
      complications. However, there is no statistical difference between operative and
      nonoperative treatment in terms of clinical outcomes.

PMID- 26312460
TI  - Is Coonrad-Morrey total elbow arthroplasty a viable option for treatment of
      distal humeral nonunions in the elderly?
AB  - OBJECTIVE: The purpose of this study was to evaluate the functional and
      radiological results of semiconstrained Coonrad-Morrey total elbow arthroplasty
      for distal humeral nonunions in the mid-term period. METHODS: Seven patients were
      treated with Coonrad-Morrey total elbow arthroplasty for distal humeral nonunion.
      All patients were female, and the mean age was 65.6 years (range: 64-68 years).
      Patients were followed for at least 5 years, and the mean follow-up time was 73
      months (range: 63-84 months). Anteroposterior and lateral radiographs at
      preoperative and early postoperative period of the joint replacement and latest
      follow-up were used to detect postoperative radiological changes in terms of
      loosening. The Mayo Elbow Performance Index (MEPI) and Q-DASH Score were used for
      functional evaluation. RESULTS: At the latest follow-up, joint stability had been
      achieved in all 7 patients. Six patients (85.7%) were pain free. The mean range
      of motion was 30 degrees  (range: 0-60 degrees ) preoperatively, and this
      improved to 90.7 degrees  (range: 60-110 degrees ) at the latest follow-up
      (p<0.05). Five patients (71.4%) had excellent or good outcomes on the MEPI. The
      mean Q-DASH Score was improved from 93.2 to 34.5 (p<0.01). Two humeral components
      had aseptic loosening, and 1 of them was revised. CONCLUSION: Semiconstrained
      total elbow arthroplasty can be a reliable choice of treatment if other internal
      fixation methods fail. Significant pain relief and improvements in elbow function
      and stability can be achieved with semiconstrained elbow arthroplasty in patients
      with distal humeral nonunion.

PMID- 26312461
TI  - Demographical, clinical, and psychological differences of patients who suffered
      hand injury accidentally and by punching glass.
AB  - OBJECTIVE: The aim of this study was to compare patients who were injured by
      punching glass with patients who were injured accidentally, according to
      demographical, clinical, and psychological parameters. METHODS: The Hand Injury
      Severity Score (HISS), the Duruoz Hand Index, the Quick Disabilities of the Arm,
      Shoulder and Hand scale (Q-DASH), the Impact of Event Scale-Revised (IES-R), the
      Adult Attention-Deficiency/Hyperactivity Scale (A-ADHS), the Borderline
      Personality Inventory (BPI), and the Beck Depression Inventory (BDI) were used
      for evaluating severity of the injury, functionality, impact of the injury on the
      patient, attention deficiency, patterns of borderline personality symptoms, and
      level of depression, respectively. RESULTS: Patients who were injured by punching
      glass were significantly younger and more likely to injure their dominant hand.
      The severity of injury and all psychological scales were significantly higher in
      patients who were injured by punching glass. CONCLUSION: Hand therapy specialists
      should be aware of potential problems in patients who were injured by punching
      glass.

PMID- 26312462
TI  - A comparison of the quality of online information about total knee arthroplasty
      available in Turkish and English: a cross-sectional study.
AB  - OBJECTIVE: The Internet has become one of the primary resources for patients to
      obtain health-related information. While the Internet continues to evolve in
      terms of coverage and technology, concerns regarding the quality of available
      information have arisen. We aimed to investigate the quality of health-related
      information on Turkish-language medical websites by comparing it to that of
      English-language medical websites, in which the subject has long been studied.
      METHODS: The English term "total knee prosthesis" and its Turkish translation,
      "total diz protezi," were searched in Google. The 1st 30 results were assessed
      using a validated tool, the LIDA (Minervation, Oxford, UK), which was designed
      for the scoring of health-related websites according to accessibility, usability,
      and reliability. RESULTS: The Turkish- and English-language websites were not
      significantly different in terms of accessibility, but the usability and
      reliability of Turkish websites were found to be significantly poorer. We found
      that the overall quality of information on Turkish websites was poor in
      comparison with that of English-language websites. CONCLUSION: In order to raise
      consciousness about this problem and improve the quality of health-related
      information, further studies on Turkish-language websites should be performed.
      Attempts should also be made in Turkish-language websites to develop website
      certification systems and/or encourage the dissemination of existing systems.

PMID- 26312463
TI  - Reduced patellofemoral and walking pain with mobile-bearing vs. fixed-bearing
      total knee replacements: a mid-term prospective analytic study.
AB  - OBJECTIVE: Total knee replacement (TKR) is the standard treatment for advanced
      stage knee osteoarthritis. The introduction of the mobile-bearing (MB) design has
      given rise to a series of theoretical advantages compared to fixed-bearing (FB)
      implants, although current literature does not reveal significant differences
      between the designs. The aim of this study was to estimate the clinical results
      of 2 cemented total knee prosthetic designs: an MB and an FB design. METHODS: A
      series of patients with similar clinical and radiographic characteristics were
      treated consecutively with 100 FB followed by 94 MB implants. Patients were
      evaluated radiographically and clinically. RESULTS: Statistically significant
      differences were found in terms of pain at 5 years in favor of MB prostheses
      (p=0.006). The "pain on ascending/descending stairs" category on the KSS score
      showed improvement at 5 years for the MB design (p=0.003). MB implants showed
      better results in terms of ability to ascend/descend stairs at five years
      (p=0.002). With regards to the patients' ability to walk, there were differences
      at 1 year (p=0.020) and at 5 years (p=0.021) in favor of MB implants. CONCLUSION:
      At a mean follow-up of 5 years, significant differences were observed in the MB
      prosthesis in terms of postoperative pain, ability to ascend/descend stairs, and
      patellofemoral pain.

PMID- 26312464
TI  - Efficacy of rapid recovery protocol for total knee arthroplasty: a retrospective
      study.
AB  - OBJECTIVE: Our aim was to compare the clinical results and cost-effectiveness of
      a rapid recovery protocol for total knee arthroplasty (TKA) with a current
      standard protocol. METHODS: The study included patients undergoing primary
      elective TKA with at least 6 months of follow-up. The rapid recovery protocol was
      applied to 96 patients (Group 1) and the standard protocol to 108 (Group 2). All
      patients underwent standard TKA. All pre-, peri-, and postoperative procedures in
      the treatment and follow-up of patients were appropriately standardized to the
      philosophies of the different treatment plans. The postoperative length of
      hospital stay, total financial cost, postoperative surgical infection, 6-month
      American Knee Society scores, and knee range of motion (ROM) were compared
      between the groups. RESULTS: A total of 169 patients were included. Group 1
      patients had significantly shorter postoperative length of hospital stay
      (p=0.021), significantly lower mean total financial cost (p=0.041), significantly
      lower infection rates (p=0.034), and significantly higher 6-month knee function
      scores (p=0.032). In comparison with Group 2, Group 1 knee flexion (p=0.04) and
      extension (p=0.48) ROM at 6 months postoperatively were both significantly
      improved. CONCLUSION: Application of the rapid recovery protocol to patients who
      underwent TKA reduced costs and infection rates and improved functional results.

PMID- 26312465
TI  - Impact of oxidative stress on early postoperative knee function and muscle injury
      biochemical markers: Is it possible to create an ischemic preconditioning effect
      in sequential ischemic surgical procedures?
AB  - OBJECTIVE: Simultaneous bilateral total knee arthroplasty (TKA) with prolonged
      tourniquet time has the potential to trigger ischemia-reperfusion injury, which
      can adversely affect knee function. Studies suggest that the magnitude of injury
      is less if it occurs following an ischemic event which takes place in another
      part of the body, known as ischemic preconditioning (IPC). The purpose of this
      study was to investigate the impact of oxidative stress on muscle injury and knee
      function and to elucidate if potential IPC effect can attenuate ischemia
      reperfusion injury metabolites and prevent poor functional outcomes in single
      stage bilateral TKA. METHODS: Thirty patients who underwent single-stage
      bilateral TKA under tourniquet were enrolled in the study. All procedures were
      initiated from the right limb. Upon completion of the procedure, the left
      tourniquet was inflated 20 minutes after the first tourniquet was deflated. The
      tourniquet time was noted. Pre- and postoperative levels of malondialdehyde
      (MDH), creatine kinase (CK), and lactate dehydrogenase (LDH) were evaluated. Knee
      function was assessed postoperatively at 1 month using WOMAC score. RESULTS:
      Postoperative levels of MDH, CK, and LDH were significantly increased in both
      extremities compared to preoperative levels. Serum MDH, CK, and LDH levels were
      not found to be correlated with tourniquet time for either extremity. Compared to
      the left extremity, the right extremity revealed increased postoperative
      oxidative stress, which was indicated by elevated serum MDH, CK, and LDH levels.
      Although tourniquet time and postoperative serum MDH, CK, and LDH levels were not
      found to be correlated with WOMAC index in either knee, the average change in
      WOMAC score at 1 month postoperatively was found to be higher in the left knee
      compared to the right. CONCLUSION: The biochemical and functional outcomes can be
      attributed to potential IPC effect. During bilateral TKA, a 20-minute interval
      between tourniquets can create IPC effect and attenuate the magnitude of ischemia
      reperfusion injury, preserving better functional outcomes.

PMID- 26312466
TI  - Immunohistochemical analysis of mechanoreceptors in transverse acetabular
      ligament and labrum: a prospective analysis of 35 cases.
AB  - OBJECTIVE: The labrum and transverse acetabular ligament (TAL) are classically
      described as distinct anatomical structures with abundant mechanoreceptors and
      free nerve fibers. They deepen the joint and act as natural barriers against
      dislocation, thus providing additional stability. We hypothesized that severe
      coxarthrosis leads to elimination of labrum and TAL mechanoreceptors. This study
      evaluated the microscopic anatomy of the labrum and TAL and specifically
      investigated the neurological status of these structures. METHODS: Labral and TAL
      specimens from 35 consecutive patients with coxarthrosis undergoing total hip
      arthroplasty were dissected into a total of 4 specimens per hip. Formaldehyde
      fixed specimens were evaluated for the presence of mechanoreceptors and free
      nerve endings by neurofilament protein and S-100 protein immunohistochemistry and
      microscopy. RESULTS: Mechanoreceptors were identified in the labral (2.3/high
      power field) but not TAL specimens, with a sharp delineation between the tissues.
      In contrast, both labrum and TAL showed good vascularity with abundant free nerve
      fibers within fibrous connective tissue (mean, 2.6 sensory fibers/ high power
      field vs 3.1/high power field, respectively). CONCLUSION: This study demonstrated
      that the TAL lacks mechanoreceptors. However, TAL and labrum free nerve fibers
      suggest potential roles as hip pain generators.

PMID- 26312467
TI  - Chevron osteotomy in patients with scheduled osteotomy of the medial malleolus.
AB  - OBJECTIVE: The aim of the present study was to evaluate intermediate-term
      outcomes of Chevron osteotomy for treatment of osteochondral lesions of the talus
      with mosaicplasty and to assess its effect on surgery and whether it reduces
      complications that might occur intraoperatively. METHODS: The present study
      included a total of 42 patients (31 men, 11 women) who underwent Chevron
      osteotomy of the medial malleolus and who had been followed for more than 2
      years. Mean age of the patients was 34 years (range: 18-54 years).
      Preoperatively, size of the lesions was measured in millimeters in the coronal
      and sagittal planes using magnetic resonance imaging (MRI). The angle between the
      osteotomy with the long axis of the tibia was measured on the coronal plane, the
      angle between the arms and the angle for the screws to be directed to the
      osteotomy line were measured on the sagittal plane on the postoperative images.
      Nonunion, malunion, and complications from the screws were evaluated from X-ray
      images taken at the final follow-up. RESULTS: Mean duration for follow-up was
      31.4 years (range: 24-46). On the X-ray images taken at the final follow-up, no
      distraction, migration of the distal part, or rotation was observed. Only 1
      patient experienced radiological non-union. Mean duration to union was 5.8 weeks
      (range: 4-14 weeks). Screws of 8 patients were removed at an average of 7.4
      months (range: 5-11 months). The angle between the osteotomy line and long axis
      of the tibia was 29.0 degrees +/-6.5 degrees , the angel between the osteotomy
      arms on the sagittal plane was 74.7 degrees +/-8.3 degrees , and the direction
      angle of the screws on the coronal plane was 85.7 degrees +/-5.9 degrees .
      CONCLUSION: Chevron osteotomy is an assistive surgical method used for treatment
      of osteochondral lesions located in the medial talar joint surface (TOL) which
      provides fast anatomical healing because it allows efficient fixation due to its
      geometry.

PMID- 26312468
TI  - Does lengthening after acute correction negatively affect bone healing during
      distraction osteogenesis?
AB  - OBJECTIVE: Lengthening after acute correction has a negative effect on bone
      healing during distraction osteogenesis. In this study, we investigated whether
      correcting an acute deformity prior to lengthening resulted in a negative effect
      on bone healing. METHODS: Patients with shortened femora were assigned to 3
      matched groups. Retrograde femoral nailing after distal metaphyseal-diaphyseal
      osteotomy was used in all cases. Group 1 (9 femora) included cases of lengthening
      >4 cm using intramedullary distraction devices after acute correction. Group 2
      (16 femora) included pure lengthening cases of >=4 cm using intramedullary
      distraction devices. Group 3 (13 femora) included cases of lengthening >=4 cm
      with lengthening and the retrograde nailing method (LORN) following acute
      correction. RESULTS: Healing indices and full weight-bearing times of patients
      were evaluated. Mean lengthening values were 6.6 (range: 4-14 cm), 5.7 (range: 4
      8 cm), and 5.2 cm (range: 4-6.5 cm) in Groups 1-3, respectively, and mean
      radiographic consolidation index and full weight-bearing times were 31.0+/-8.2,
      30.2+/-5.5, and 39.0+/-5.0 day/cm in Groups 1-3, respectively. The consolidation
      index was significantly better in the Groups 1 and 2 compared to that in Group 3,
      but no difference was detected between Groups 1 and 2. CONCLUSION: Acute
      correction had no negative effect on bone healing after distraction osteogenesis
      using new-generation intramedullary distraction devices. We suggest that the
      negative impact on healing and the prolonged consolidation index in patients
      undergoing LORN may be due to impaired periosteal blood supply due to fixator
      pins.

PMID- 26312469
TI  - Hydroxyapatite pins for external fixation: is there sufficient evidence to prove
      that coated pins are less likely to be replaced prematurely?
AB  - OBJECTIVE: Several clinical studies have reported that the use of hydroxyapatite-
      (HA) coated pins enhance external fixation. Although these studies have
      demonstrated higher extraction torques and lower rates of pin loosening with HA
      coating, there is little evidence to suggest that these biomechanical advantages
      translate to a lower rate of pin replacement prior to healing. The research
      question posed was "Is there sufficient evidence to prove that hydroxyapatite
      coating lowers the rate of pin replacement for external fixation?" METHODS: An
      electronic search of Medline (Ovid, 1946 - December Week 4 2011), Embase (Ovid,
      1980-2011 Week 52), and the Cochrane Central Register of Controlled Trials (Issue
      4 of 4, October 2011) was conducted to identify all randomized and quasi
      randomized controlled trials which compared HA-coated pins with non-coated pins
      for external fixation, with particular emphasis on the premature replacement of
      pins as a consequence of loosening. RESULTS: The combined search strategies
      retrieved 72 citations. Four randomized controlled trials (101 patients, 327 HA
      coated vs. 354 uncoated pins) were included in this review. None of the studies
      demonstrated a clear benefit between pin types with respect to premature
      replacement of pins prior to healing. CONCLUSION: This review did not find
      sufficient evidence to validate the preferential use of HA-coated pins over
      standard pins as a means of avoiding premature replacement of pins used for
      external fixation. The use of uncoated pins is justifiable, especially within the
      context of limited financial resources.

PMID- 26312470
TI  - Bonesetter interventions and consequences.
AB  - OBJECTIVE: Delaying the treatment of bone and tendon injuries may cause
      unmanageable complications. Bonesetters continue to cause delays in treatment.
      The purpose of this study was to analyze the medical outcomes of delay due to
      bonesetter intervention and factors affecting patient treatment preference.
      METHODS: Among outpatients treated at our clinic between January 2010-December
      2012, bonesetter-intervened patients were included, and patient demographics,
      clinical outcomes, and possible social factors were retrospectively analyzed.
      Clinical examinations and radiological screening measurements were used to
      evaluate outcomes. RESULTS: Of the 162 patients, 97 (59.8%) were male, and mean
      age was 27.5+/-9.4 years. Eighty-nine (54.9%) of the patients lived in a rural
      area, and 108 (66.7%) underwent surgery. Bonesetter preference was dictated
      primarily by elderly relatives (47.6%) or neighbors (33.3%). Patients with a
      primary school education and unemployed patients mostly preferred bonesetters
      (p=0.03 and p<0.01, respectively), the explanation for which was the long
      treatment period and concern of being disabled (p=0.04). Complication rate among
      patients who were evaluated at a hospital was 33.9%. CONCLUSION: Despite being
      medically unreliable and often times harmful, bonesetting is still accepted as an
      alternative treatment modality among uneducated patient and thus remains an
      ongoing problem in Turkey. Improvements in average education level and increased
      dissemination of accurate information via various media and non-governmental
      organizations will be effective in the correction and prevention of the afore
      mentioned complications regarding bonesetter interventions.

PMID- 26312471
TI  - Surgical light handles: a source of contamination in the surgical field.
AB  - OBJECTIVE: Total hip arthroplasty (THA) is a common and generally safe procedure;
      however, among the most devastating complications associated with THA is
      periprosthetic infection (PPI). The origin of bacteria causing PPI is not
      completely understood. The aims of the present study were to identify bacterial
      contamination of light handles with up-to-date culture methods and to determine
      the safety in using these handles in hip arthroplasty surgery. METHODS: A total
      of 36 surgical handles randomly selected from primary hip arthroplasty procedures
      were screened for bacterial contamination using 2 different culture methods,
      including 1 with high sensitivity. Two types of controls were used. Cultures were
      kept for up to 10 days, and retrieved bacteria were identified. RESULTS: Fifty
      percent of the light handles yielded positive cultures, demonstrating a bacterial
      presence on surgical light handles during hip arthroplasty. The most frequently
      identified bacteria were Staphylococcus epidermidis and Staphylococcus aureus.
      CONCLUSION: A large number of positive bacterial cultures were found in
      manipulated light handles during hip replacement surgery, representing a
      potential contamination source that could eventually lead to infection in hip
      arthroplasty.

PMID- 26312472
TI  - Biomechanical outcome of proximal femoral nail antirotation is superior to
      proximal femoral locking compression plate for reverse oblique intertrochanteric
      fractures: a biomechanical study of intertrochanteric fractures.
AB  - OBJECTIVE: Reverse obliquity intertrochanteric fractures are a challenge for
      orthopedic surgeons. The optimal internal fixation for repairing this type of
      unstable intertrochanteric fractures remains controversial. This study aimed to
      compare the biomechanical properties in axial load and cyclical axial load of
      proximal femoral nail antirotation (PFNA) and proximal femoral locking
      compression plate (PFLCP) for fixation of reverse obliquity intertrochanteric
      fractures. METHODS: Sixteen embalmed cadaver femurs were sawed to simulate
      reverse obliquity intertrochanteric fracture and instrumented with PFNA or PFLCP.
      Axial loads and axial cyclic loads were applied to the femoral head by an Instron
      tester. If the implant-femur constructs did not fail, axial failure load was
      added to the remaining implant-femur constructs. RESULTS: Mean axial stiffness
      for PFNA was 21.10% greater than that of PFLCP. Cyclic axial loading caused
      significantly less (p=0.022) mean irreversible deformation in PFNA (3.43 mm) than
      in PFLCP (4.34 mm). Significantly less (p=0.002) mean total deformation was
      detected in PFNA (6.16 mm) than in PFLCP (8.67 mm). CONCLUSION: For fixing
      reverse obliquity intertrochanteric fractures, PFNA is superior to PFLCP under
      axial load.

PMID- 26312473
TI  - Anatomical relations between anterior coracoscapular ligament and suprascapular
      neurovascular structures and a proposal for classification.
AB  - OBJECTIVE: Although suprascapular nerve entrapment is rare, the most common site
      of compression is the suprascapular notch. The anterior coracoscapular ligament
      (ACSL), which lies inferior to the superior transverse scapular ligament (STSL),
      may also be a cause of entrapment. We aimed to investigate the presence of ACSL
      and its relations to the suprascapular nerve and vessels. METHODS: We dissected
      50 shoulders of 26 cadavers. We excluded 2 shoulders due to previous shoulder
      surgery. We observed the course of the suprascapular nerve, artery, and vein(s),
      and examined whether they passed between STSL and ACSL or under ACSL. We
      classified the anatomical relations between neurovascular structures, STSL, and
      ACSL. In Type I, the suprascapular nerve passed between STSL and ACSL; in Type
      Iia, the suprascapular nerve and a single suprascapular vein passed between STSL
      and ACSL; in Type Iib, a suprascapular vein passed under ACSL and the
      suprascapular nerve passed between STSL and ACSL; in Type III, the suprascapular
      artery, vein, and nerve passed between STSL and ACSL. RESULTS: ACSL was present
      in 16 shoulders (32%). The suprascapular nerve passed between STSL and ACSL in
      all cases. We observed Type I, Type Iia, Type Iib, and Type III anatomical
      relations in 14%, 12%, 2%, and 4% of cases, respectively. CONCLUSION: Vascular
      structures that pass under STSL may cause suprascapular nerve entrapment.
      Presence of ACSL with vessel(s) passing under it and/or between it and STSL may
      increase the risk of nerve entrapment.

PMID- 26312474
TI  - Comparison of the effects of chronic intra-articular administration of tenoxicam,
      diclofenac, and methylprednisolone in healthy rats.
AB  - OBJECTIVE: Lyophilized drug manufacturing and intra-articular (IA) applications
      have increased to address gastrointestinal side effects resulting from chronic
      treatment with non-steroidal anti-inflammatory drugs (NSAIDs) for degenerative
      joint disease. Accordingly, we histologically examined joint and stomach tissues
      from rats to determine and compare the effects of long-term treatment with an IA
      corticosteroid (methylprednisolone acetate), lyophilized NSAID (tenoxicam), and
      non-lyophilized NSAID (diclofenac) following application to the knee joint.
      METHODS: One hundred Wistar albino rats were divided into 4 groups of 25 rats:
      control, methylprednisolone, tenoxicam, and diclofenac. Ten IA injections were
      administered at 1-week intervals. Rats were sacrificed at 48 h and 1, 2, 4, and 8
      weeks after the tenth injection. Histomorphologically, knee joint samples were
      examined for osteoarthritic changes and stomach tissue samples for gastric
      changes. RESULTS: Unlike methylprednisolone, diclofenac and tenoxicam caused
      increased fibrosis and fibroblast production; furthermore, chronic
      methylprednisolone use had no negative effects on the synovium or cartilage.
      CONCLUSION: Chronic tenoxicam and diclofenac use affects joints more negatively
      than chronic steroid treatment.

PMID- 26312475
TI  - Effect of intramuscular botulinum toxin-A in a rat rotator cuff repair model: an
      experimental study.
AB  - OBJECTIVE: Rotator cuff repair is associated with multiple complications,
      significant morbidity, and reintervention, which could be mitigated by
      postoperative chemodeneveration with botulinum toxin-A (BTX-A). This study
      evaluated the antinociceptive and paralytic effects of BTX-A on an experimental
      supraspinatus repair rat model and its effect on functional outcomes (running
      performance). METHODS: Thirty rats were grouped into the surgical repair group
      (group A), repair + intramuscular BTX-A group (group B), or control group (group
      C). At the end of the 3-month follow-up, running performance of the rats on a
      motorized treadmill was evaluated in four time periods (0-30 min, 30-60 min, 60
      90 min, and 90-110 min), and penalty points (i.e., number of shock stimuli per
      lane) were recorded. Afterwards, the supraspinatus muscles were removed and
      evaluated histologically. RESULTS: Regarding running performance, group B
      received significantly fewer penalty points than did group A (p<0.05). The
      penalty points received were not significantly different between groups B and C
      in the first three time periods, but were significantly higher in group B at the
      90-110-min interval than in group C. On necropsy, all repaired tendons were
      intact, with no sign of failure at the repair site. Histological evaluation
      revealed marked degeneration and necrosis of muscles in both repair groups, which
      was much less evident in group B. Groups A and B had less fatty infiltration than
      group C. CONCLUSION: BTX-A injections resulted in a better function based on
      running performance, probably due to decreased tissue tension at the repair site
      and less pain. Further studies on humans are needed to demonstrate this effect
      clinically.

PMID- 26312476
TI  - Cervical digits: a report of 3 cases.
AB  - The occurence of digit like structures around vertebral column is a rare and only
      one case in the cervical region has been reported before. Here we report three
      more cases of cervical digits with computed tomography and magnetic resonance
      imaging correlations as the first cases of the literature. 

PMID- 26312477
TI  - Bilateral internal pudendal artery-urethral fistula formation by pseudoaneurysm.
AB  - Posttraumatic fistula between the internal pudendal artery and urethra is rarely
      reported in the literature. We report a case of bilateral internal pudendal
      artery-urethral fistula formation by pseudoaneurysm, following a blunt pelvic
      trauma in which superselective angiography revealed the site of bleeding. The
      fistula was treated with superselective arterial embolization. 

PMID- 26312478
TI  - Spinal epidural cavernous angioma: two case reports and review of the literature.
AB  - Cavernous angiomas are vascular malformations that occur most frequently in the
      supratentorial area of the central nervous system (CNS). Spinal epidural
      occurrence is rare. This article describes 2 cases of spinal epidural cavernous
      angioma. The lesions were hypo- to isointense on T1-weighted magnetic resonance
      images (MRIs) and hyperintense on T2-weighted images. Both were enhanced
      homogenously with intravenous contrast. Total resection was achieved in both
      cases, and the lesions were histopathologically diagnosed as cavernous angiomas.
      The patients' symptoms regressed postsurgery. Although the MRI features of
      cavernous angiomas are well known, spinal epidural occurrence is rare and many
      differential diagnoses have similar clinical and imaging findings. It is
      important to definitively diagnose these lesions prior to surgery in order to
      prevent possible intraoperative complications such as massive bleeding and to
      maximize chances for complete resection. In addition to case descriptions, this
      article includes a thorough literature review to raise clinical awareness about
      this well-known but rare spinal entity. 

PMID- 26312479
TI  - Ultrasensitive and specific measurement of protease activity using functionalized
      photonic crystals.
AB  - Herein is presented a microsensor technology as a diagnostic tool for detecting
      specific matrix metalloproteinases (MMPs) at very low concentrations. MMP-2 and
      MMP-9 are detected using label free porous silicon (PSi) photonic crystals that
      have been made selective for a given MMP by filling the nanopores with synthetic
      polymeric substrates containing a peptide sequence for that MMP. Proteolytic
      cleavage of the peptide sequence results in a shift in wavelength of the main
      peak in the reflectivity spectrum of the PSi device, which is dependent on the
      amount of MMP present. The ability to detect picogram amounts of MMP-2 and MMP-9
      released by primary retinal pigment epithelial (RPE) cells and iris pigment
      epithelial (IPE) cells stimulated with lipopolysaccharide (LPS) is demonstrated.
      It was found that both cell types secrete higher amounts of MMP-2 than MMP-9 in
      their stimulated state, with RPE cells producing higher amounts of MMPs than IPE
      cells. The microsensor performance was compared to conventional protease
      detection systems, including gelatin zymography and enzyme linked immunosorbent
      assay (ELISA). It was found that the PSi microsensors were more sensitive than
      gelatin zymography; PSi microsensors detected the presence of both MMP-2 and MMP
      9 while zymography could only detect MMP-2. The MMP-2 and MMP-9 quantification
      correlated well with the ELISA. This new method of detecting protease activity
      shows superior performance to conventional protease assays and has the potential
      for translation to high-throughput multiplexed analysis. 

PMID- 26312480
TI  - Treatment-Induced Changes in Plasma Adiponectin Do Not Reduce Urinary Albumin
      Excretion in the Diabetes Prevention Program Cohort.
AB  - BACKGROUND AND OBJECTIVES: Molecular data suggests that adiponectin may directly
      regulate urinary albumin excretion. In the Diabetes Prevention Program (DPP) we
      measured adiponectin and albuminuria before and after intervention, and we
      previously reported increases in adiponectin with interventions. Here we have
      used the DPP dataset to test the hypothesis that treatment-related increases in
      adiponectin may reduce albuminuria in obesity. DESIGN, SETTING, PARTICIPANTS AND
      METHODS: We evaluated cross-sectional correlations between plasma adiponectin and
      urinary albumin excretion at baseline, and the relationship of treatment-related
      changes in adiponectin and albuminuria. Baseline and follow-up urine albumin to
      creatinine ratios (ACR (albumin to creatinine ratio)) and plasma adiponectin
      concentration were available in 2553 subjects. RESULTS: Adjusting for age, sex
      and race/ethnicity, we observed a statistically significant but weak inverse
      relationship between adiponectin and ACR at baseline (conditional Spearman's rho
      = (-) 0.04, p = 0.04). Although DPP treatments significantly increased plasma
      adiponectin, there were no treatment effects on ACR and no differences in ACR
      across treatment groups. There was a weak direct (not inverse) association
      between change in adiponectin and change in albuminuria (adjusted Spearman's rho
      = (+) 0.04, p = 0.03). CONCLUSIONS: In a large, well-characterized cohort of
      obese dysglycemic subjects we observed a weak inverse association between
      circulating adiponectin concentrations and urinary albumin excretion at baseline.
      Contrary to the hypothesized effect, treatment-related increases in plasma
      adiponectin were not associated with a reduction in ACR. The association of
      change in adiponectin with change in ACR should be assessed in populations with
      overt albuminuria before excluding a beneficial effect of increasing adiponectin
      to reduce ACR in obesity.

PMID- 26312481
TI  - Prediction of Functionally Important Phospho-Regulatory Events in Xenopus laevis
      Oocytes.
AB  - The African clawed frog Xenopus laevis is an important model organism for studies
      in developmental and cell biology, including cell-signaling. However, our
      knowledge of X. laevis protein post-translational modifications remains scarce.
      Here, we used a mass spectrometry-based approach to survey the phosphoproteome of
      this species, compiling a list of 2636 phosphosites. We used structural
      information and phosphoproteomic data for 13 other species in order to predict
      functionally important phospho-regulatory events. We found that the degree of
      conservation of phosphosites across species is predictive of sites with known
      molecular function. In addition, we predicted kinase-protein interactions for a
      set of cell-cycle kinases across all species. The degree of conservation of
      kinase-protein interactions was found to be predictive of functionally relevant
      regulatory interactions. Finally, using comparative protein structure models, we
      find that phosphosites within structured domains tend to be located at positions
      with high conformational flexibility. Our analysis suggests that a small class of
      phosphosites occurs in positions that have the potential to regulate protein
      conformation. 

PMID- 26312483
TI  - Correction: Genetic Evaluation of Dual-Purpose Buffaloes (Bubalus bubalis) in
      Colombia Using Principal Component Analysis.

PMID- 26312482
TI  - Improved Assay for Quantifying a Redox Form of Angiotensinogen as a Biomarker for
      Pre-Eclampsia: A Case-Control Study.
AB  - OBJECTIVE: Angiotensinogen exists in two distinct redox forms in plasma, the
      oxidized sulfhydryl-bridge form and the reduced, unbridged, free thiol form. The
      oxidized form of angiotensinogen compared to the free thiol form preferentially
      interacts with renin resulting in increased generation of angiotensin. The
      predictive potential of the ratio of free-thiol to oxidized angiotensinogen in
      the plasma for pre-eclampsia was first suggested by the Read group in ref 10. We
      propose an improved method for determining the ratio and validate the method in a
      larger cohort of pregnant women. METHODS: Plasma samples from 115 individuals
      with pre-eclampsia and from 55 healthy pregnant control subjects were collected
      sequentially over a 2 year period. Using two distinct enzyme-linked immunosorbent
      assays (ELISAs) the plasma levels of total and free thiol angiotensinogen were
      quantified. The oxidized angiotensinogen plasma level is derived by subtracting
      the level of free thiol, reduced angiotensinogen from the total angiotensinogen
      levels in the plasma. RESULTS: The relative proportion of free thiol
      angiotensinogen, expressed as a percentage of that observed with an in-house
      standard, is significantly decreased in pre-eclamptic patients (70.85% +/-
      29.49%) (mean +/- SD) as compared to healthy pregnant controls (92.98 +/- 24.93%)
      (mean +/- SD) p <= 0.0001. The levels of total angiotensinogen did not differ
      between the two groups. CONCLUSION: Patients with pre-eclampsia had substantially
      lower levels of free thiol angiotensinogen compared to healthy pregnant controls,
      whilst maintaining similar total angiotensinogen levels in the plasma. Hence,
      elevated levels of plasma oxidized angiotensinogen may be a contributing factor
      to hypertension in the setting of pre-eclampsia.

PMID- 26312484
TI  - Relationship between Sevoflurane Plasma Concentration, Clinical Variables and
      Bispectral Index Values during Cardiopulmonary Bypass.
AB  - BACKGROUND: Anesthetic administration is increasingly guided by
      electroencephalography (EEG)-based monitoring, such as the bispectral index
      (BIS). However, during cardiopulmonary bypass (CPB), factors other than the
      administered hypnotic agents may influence EEG signals, and their effects on BIS
      values are unknown. METHODS: This report is a secondary analysis of data from a
      prospective, controlled interventional study comparing the effect of sevoflurane
      administration guided by BIS monitoring (group SevoBIS) and constant
      administration of sevoflurane (group Sevo1.8Vol%) during CPB. Sevoflurane plasma
      concentration (SPC) was measured using gas chromatography. The relationships of
      BIS to SPC, CPB pump flow, arterial pressure, hematocrit, temperature, time on
      CPB, and patient characteristics were analysed. RESULTS: No association was
      observed between BIS values and SPC in group SevoBIS. In group Sevo1.8Vol%, a 40
      MUg ml-1 increase in SPC, which encompassed the entire range of observed values
      of the SPC in this analysis, was associated with a decrease of 3.6 (95%
      confidence interval (CI): 1.1-6.1) in BIS values (p = 0.005). Each increase in
      CPB time of 10 minutes was associated with an increase in BIS values of 0.25
      (95%CI: 0.11-0.39, p<0.001). Path analysis revealed that the BIS values of
      SevoBIS patients were 5.3 (95%CI: 3.2-7.5) units higher than those of Sevo1.8Vol%
      patients (p<0.001), which was the strongest effect on BIS values. Path analysis
      revealed a slope of 0.5 (95%CI: 0.3-0.7) BIS units per 1 degrees C body
      temperature (p<0.001). CONCLUSION: BIS monitoring is insensitive to clinically
      relevant changes in SPC in individual patients during CPB.

PMID- 26312486
TI  - Experimental Evidence on Iterated Reasoning in Games.
AB  - We present experimental evidence on two forms of iterated reasoning in games,
      i.e. backward induction and interactive knowledge. Besides reliable estimates of
      the cognitive skills of the subjects, our design allows us to disentangle two
      possible explanations for the observed limits in performed iterated reasoning:
      Restrictions in subjects' cognitive abilities and their beliefs concerning the
      rationality of co-players. In comparison to previous literature, our estimates
      regarding subjects' skills in iterated reasoning are quite pessimistic. Also, we
      find that beliefs concerning the rationality of co-players are completely
      irrelevant in explaining the observed limited amount of iterated reasoning in the
      dirty faces game. In addition, it is demonstrated that skills in backward
      induction are a solid predictor for skills in iterated knowledge, which points to
      some generalized ability of the subjects in iterated reasoning. 

PMID- 26312485
TI  - Exploring Genomic, Geographic and Virulence Interactions among Epidemic and Non
      Epidemic St. Louis Encephalitis Virus (Flavivirus) Strains.
AB  - St. Louis encephalitis virus (SLEV) is a re-emerging arbovirus in South America.
      In 2005, an encephalitis outbreak caused by SLEV was reported in Argentina. The
      reason for the outbreak remains unknown, but may have been related to virological
      factors, changes in vectors populations, avian amplifying hosts, and/or
      environmental conditions. The main goal of this study was to characterize the
      complete genome of epidemic and non-epidemic SLEV strains from Argentina.
      Seventeen amino acid changes were detected; ten were non-conservative and located
      in proteins E, NS1, NS3 and NS5. Phylogenetic analysis showed two major clades
      based on geography: the North America and northern Central America (NAnCA) clade
      and the South America and southern Central America (SAsCA) clade. Interestingly,
      the presence of SAsCA genotype V SLEV strains in the NAnCA clade was reported in
      California, Florida and Texas, overlapping with known bird migration flyways.
      This work represents the first step in understanding the molecular mechanisms
      underlying virulence and biological variation among SLEV strains. 

PMID- 26312487
TI  - Activation of p38 Mitogen-Activated Protein Kinase in Gaucher's Disease.
AB  - Gaucher's disease is caused by defects in acid beta-glucosidase 1 (GBA1) and has
      been also proposed as an inflammatory disease. GBA1 cleaves glucosylceramide to
      form ceramide, an established bioactive lipid, and defects in GBA1 lead to
      aberrant accumulation in glucosylceramide and insufficient formation of ceramide.
      We investigated if the pro-inflammatory kinase p38 is activated in Gaucher's
      disease, since ceramide has been proposed to suppress p38 activation. Three
      Gaucher's disease mouse models were employed, and p38 was found to be activated
      in lung and liver tissues of all Gaucher's disease mice. Most interestingly,
      neuronopathic Gaucher's disease type mice, but not non-neuronopathic ones,
      displayed significant activation of p38 and up-regulation of p38-inducible
      proinflammatory cytokines in brain tissues. In addition, all type of Gaucher's
      disease mice also showed increases in serum IL-6. As cellular signalling is
      believed to represent an in vivo inflammatory phenotype in Gaucher's disease,
      activation of p38 and possibly its-associated formation of proinflammatory
      cytokines were assessed in fibroblasts established from neuronopathic Gaucher's
      disease mice. In mouse Gaucher's disease cells, p38 activation and IL-6 formation
      by TNF-alpha treatment were enhanced as compared to those of wild type.
      Furthermore, human fibroblasts from Gaucher's disease patients also displayed
      increases in p38 activation and IL-6 formation as comparison to healthy
      counterpart. These results raise the potential that proinflammatory responses
      such as p38 activation and IL-6 formation are augmented in Gaucher's disease. 

PMID- 26312488
TI  - Effects of Deep Brain Stimulation on the Lived Experience of Obsessive-Compulsive
      Disorder Patients: In-Depth Interviews with 18 Patients.
AB  - Deep Brain Stimulation (DBS) is a relatively new, experimental treatment for
      patients suffering from treatment-refractory Obsessive Compulsive Disorder (OCD).
      The effects of treatment are typically assessed with psychopathological scales
      that measure the amount of symptoms. However, clinical experience indicates that
      the effects of DBS are not limited to symptoms only: patients for instance report
      changes in perception, feeling stronger and more confident, and doing things
      unreflectively. Our aim is to get a better overview of the whole variety of
      changes that OCD patients experience during DBS treatment. For that purpose we
      conducted in-depth, semi-structured interviews with 18 OCD patients. In this
      paper, we present the results from this qualitative study. We list the changes
      grouped in four domains: with regard to (a) person, (b) (social) world, (c)
      characteristics of person-world interactions, and (d) existential stance. We
      subsequently provide an interpretation of these results. In particular, we
      suggest that many of these changes can be seen as different expressions of the
      same process; namely that the experience of anxiety and tension gives way to an
      increased basic trust and increased reliance on one's abilities. We then discuss
      the clinical implications of our findings, especially with regard to properly
      informing patients of what they can expect from treatment, the usefulness of
      including CBT in treatment, and the limitations of current measures of treatment
      success. We end by making several concrete suggestions for further research. 

PMID- 26312489
TI  - Enzyme-Free Detection of Mutations in Cancer DNA Using Synthetic Oligonucleotide
      Probes and Fluorescence Microscopy.
AB  - BACKGROUND: Rapid reliable diagnostics of DNA mutations are highly desirable in
      research and clinical assays. Current development in this field goes
      simultaneously in two directions: 1) high-throughput methods, and 2) portable
      assays. Non-enzymatic approaches are attractive for both types of methods since
      they would allow rapid and relatively inexpensive detection of nucleic acids.
      Modern fluorescence microscopy is having a huge impact on detection of
      biomolecules at previously unachievable resolution. However, no straightforward
      methods to detect DNA in a non-enzymatic way using fluorescence microscopy and
      nucleic acid analogues have been proposed so far. METHODS AND RESULTS: Here we
      report a novel enzyme-free approach to efficiently detect cancer mutations. This
      assay includes gene-specific target enrichment followed by annealing to
      oligonucleotides containing locked nucleic acids (LNAs) and finally, detection by
      fluorescence microscopy. The LNA containing probes display high binding affinity
      and specificity to DNA containing mutations, which allows for the detection of
      mutation abundance with an intercalating EvaGreen dye. We used a second probe,
      which increases the overall number of base pairs in order to produce a higher
      fluorescence signal by incorporating more dye molecules. Indeed we show here that
      using EvaGreen dye and LNA probes, genomic DNA containing BRAF V600E mutation
      could be detected by fluorescence microscopy at low femtomolar concentrations.
      Notably, this was at least 1000-fold above the potential detection limit.
      CONCLUSION: Overall, the novel assay we describe could become a new approach to
      rapid, reliable and enzyme-free diagnostics of cancer or other associated DNA
      targets. Importantly, stoichiometry of wild type and mutant targets is conserved
      in our assay, which allows for an accurate estimation of mutant abundance when
      the detection limit requirement is met. Using fluorescence microscopy, this
      approach presents the opportunity to detect DNA at single-molecule resolution and
      directly in the biological sample of choice.

PMID- 26312491
TI  - Pediatric disaster preparedness and response and the nation's children's
      hospitals.
AB  - OBJECTIVE: Children account for 30 percent of the US population; as a result,
      many victims of disaster events are children. The most critically injured
      pediatric victims would be best cared for in a tertiary care pediatric hospital.
      The Children's Hospital Association (CHA) undertook a survey of its members to
      determine their level of readiness to respond to a mass casualty disaster.
      DESIGN: The Disaster Response Task Force constructed survey questions in October
      2011. SETTING AND PARTICIPANTS: The survey was distributed via e-mail to the
      person listed as an "emergency manager/disaster contact" at each association
      member hospital and was designed to take less than 15 minutes to complete. MAIN
      OUTCOME MEASURES: The survey sought to determine how children's hospitals address
      disaster preparedness, how prepared they feel for disaster events, and how CHA
      could support their efforts in preparedness. RESULTS: One hundred seventy-nine
      surveys were distributed with a 36 percent return rate. Seventy percent of
      respondent hospitals have a structure in place to plan for disaster response.
      There was a stronger level of confidence for hospitals in responding to local
      casualty events than for those responding to large-scale regional, national, and
      international events. Few hospitals appear to interact with nonmedical facilities
      with a high concentration of children such as schools or daycares. CONCLUSIONS:
      Little commonality exists among children's hospitals in approaches to disaster
      preparedness and response. Universally, respondents can identify a disaster
      response plan and routinely participate in drills, but the scale and scope of
      these plans and drills vary substantially.

PMID- 26312490
TI  - A Short Peptide That Mimics the Binding Domain of TGF-beta1 Presents Potent Anti
      Inflammatory Activity.
AB  - The transforming growth factor beta 1 (TGF-beta1) is a pleiotropic cytokine with
      multiple roles in development, wound healing, and immune regulation. TGF-beta1
      mediated immune dysfunction may lead to pathological conditions, such as
      inflammation. Chronic inflammatory process is characterized by a continuous
      release of pro-inflammatory cytokines, and the inhibition or the blockage of
      these cytokines signaling pathways are considered a target treatment. In this
      context, despite the high numbers of TGF-beta-targeted pathways, the inducible
      regulatory T cells (iTreg) to control inflammation seems to be a promising
      approach. Our aim was to develop novel peptides through phage display (PhD)
      technology that could mimic TGF-beta1 function with higher potency. Specific
      mimetic peptides were obtained through a PhD subtraction strategy from whole cell
      binding using TGF-beta1 recombinant as a competitor during elution step. We have
      selected a peptide that seems to play an important role on cellular
      differentiation and modulation of TNF-alpha and IL-10 cytokines. The synthetic
      pm26TGF-beta1 peptide tested in PBMC significantly down-modulated TNF-alpha and
      up-regulated IL-10 responses, leading to regulatory T cells (Treg) phenotype
      differentiation. Furthermore, the synthetic peptide was able to decrease
      leukocytes rolling in BALB/C mice and neutrophils migration during inflammatory
      process in C57BL/6 mice. These data suggest that this peptide may be useful for
      the treatment of inflammatory diseases, especially because it displays potent
      anti-inflammatory properties and do not exhibit neutrophils' chemoattraction. 

PMID- 26312492
TI  - Assessment of the accuracy of the Medical Response to Major Incidents (MRMI)
      course for interactive training of the response to major incidents and disasters.
AB  - BACKGROUND AND AIMS: The benefit of simulation models for interactive training of
      the response to major incidents and disasters has been increasingly recognized
      during recent years and a variety of such models have been reported. However,
      reviews of this literature show that the majority of these reports have been
      characterized by significant limitations regarding validation of the accuracy of
      the training related to given objectives. In this study, precourse and postcourse
      self-assessment surveys related to the specific training objectives, as an
      established method for curriculum validation, were used to validate the accuracy
      of a course in Medical Response to Major Incidents (MRMI) developed and organized
      by an international group of experts under the auspices of the European Society
      for Trauma and Emergency Surgery. METHODS: The studied course was an interactive
      course, where all trainees acted in their normal roles during two full-day
      simulation exercises with real time and with simultaneous training of the whole
      chain of response: scene, transport, the different functions in the hospital,
      communication, coordination, and command. The key component of the system was a
      bank of magnetized casualty cards, giving all information normally available as a
      base for decisions on triage and primary management. All treatments were
      indicated with attachments on the cards and consumed time and resources as in
      reality. The trainees' performance was recorded according to prepared protocols
      and a measurable result of the response could be registered. This study was based
      on five MRMI courses in four different countries with altogether 235 participants
      from 23 different countries. In addition to conventional course evaluations and
      recording of the performance during the 2 exercise days, the trainees' perceived
      competencies related to the specific objectives of the training for different
      categories of staff were registered on a floating scale 1-10 in self-assessment
      protocols immediately before and after the course. The results were compared as
      an indicator of to which extent the training fulfilled the given objectives.
      These objectives were set by an experienced international faculty and based on
      experiences from recent major incident and disasters. RESULTS: Comparison of
      precourse and postcourse self-assessments of the trainees' perceived knowledge
      and skills related to the given objectives for the training showed a significant
      increase in all the registered parameters for all categories of participating
      staff. The average increase was for prehospital staff 74 percent (p<0.001),
      hospital staff 65 percent (p<0.001), and staff in coordinating/administrative
      functions 81 percent (p<0.001). CONCLUSIONS: The significant differences in the
      trainees' self-assessment of perceived competencies between the precourse and
      postcourse surveys indicated that the methodology in the studied course model
      accurately responded to the specific objectives for the different categories of
      staff.

PMID- 26312493
TI  - Modernizing stockpiles of medical countermeasures against smallpox: Benefits,
      risks, and knowledge gaps.
AB  - OBJECTIVE: New smallpox medical countermeasures are entering the marketplace,
      offering the opportunity to modernize existing stockpiles. However, new smallpox
      countermeasures are developed under the animal rule, meaning that human efficacy
      data are lacking, and human safety data may be limited. Also, stockpile
      modernization would require prioritization of increasingly limited public funds.
      Approaches to address these issues are needed. METHODS: Smallpox vaccine data
      were gathered by literature search. The financial value of vaccination in the
      face of an outbreak was evaluated using a threatbased cost/benefit analysis
      model, involving i) estimation of the efficacy of new smallpox vaccines based on
      available clinical data on virus-neutralizing seroconversion in vaccinees, ii)
      estimation of the likelihood for a smallpox outbreak in Denmark, and iii)
      estimation of the expected life-saving effects of postevent vaccination. RESULTS:
      The authors estimated that i) the likelihood of a smallpox outbreak in Denmark is
      very low (one event in 200,000 years), ii) the expected efficacy of currently
      available and new vaccines is 95 and 75 percent, respectively, iii) the expected
      frequency of serious side effects from vaccination is between 100 and 10,000 fold
      lower for new than for existing vaccines, depending on modes of action.
      CONCLUSIONS: Despite the very low likelihood for a smallpox outbreak, the
      potentially large consequences combined with the protective effect of vaccination
      make maintenance of the smallpox vaccine stockpile justified and valuable. For
      vaccination in the face of a smallpox outbreak, a high efficacy rather than a
      lowered rate of adverse effects would maximize the number of lives saved.

PMID- 26312494
TI  - The Ebola Spatial Care PathTM: Accelerating point-of-care diagnosis, decision
      making, and community resilience in outbreaks.
AB  - OBJECTIVES: To present a vision where point-of-care testing (POCT) accelerates an
      Ebola Spatial Care PathTM (SCP) and future molecular diagnostics enable
      facilitated-access self-testing (FAST POC); to design an alternate care facility
      (ACF) for the SCP; to innovate an Ebola diagnostic center (DC); and to propel
      rapid POCT to the frontline to create resilience that stops future outbreaks.
      DESIGN: PubMed, literature, and web searches. Centers for Disease Control and
      Prevention (CDC), Food and Drug Administration (FDA), Medicine Without Frontiers,
      and World Health Organization (WHO) document analyses. Investigations in China,
      the Philippines, Thailand, and the United States. Review of SE Asia, US, and West
      Africa isolation-treatment centers. Innovation of a SCP, ACF, and DC suitable for
      American and other communities. OUTCOMES: The authors designed an ACF and DC to
      integrate SCP principles for urgent Ebola care. FDA emergency use authorizations
      for Ebola molecular diagnostics were discovered, but no portable, handheld, or
      self-contained molecular POC instruments are yet available, although feasible.
      The WHO initiated design criteria and an acceptance protocol for testing.
      Financial investment in POCT will downsize Ebola outbreaks. CONCLUSIONS: POCT is
      facilitating global health. Now, global health problems are elevating POCT to new
      levels of importance for accelerating diagnosis and evidence-based decision
      making during disease outbreaks. Authorities concur that rapid diagnosis has
      potential to stop disease spread. With embedded POCT, strategic SCPs planned by
      communities fulfill CDC recommendations. POC devices should consolidate multiplex
      test clusters supporting patients with Ebola in isolation. The ultimate future
      solution is FAST POC. New technologies offer minimally significant risks.
      Diagnostic centers in ACFs and transportable formats also will optimize Ebola
      SCPs.

PMID- 26312495
TI  - Proposal for a community-based disaster management curriculum for medical school
      undergraduates in Saudi Arabia.
AB  - OBJECTIVES: Health professional preparedness is a key element of disaster
      response; overall there is a need for increased disaster medicine training
      worldwide. The objective of this study was to design and develop a curriculum in
      community-based disaster medicine for Saudi Arabian medical undergraduates.
      METHODS: A structured five-step approach was used to develop a curriculum. Expert
      stakeholders from the Saudi Arabian and international disaster medicine
      communities were surveyed to determine objectives and content. Learning
      strategies were carefully considered to maximize participation and retention.
      Particular attention was paid to equipping learners with the teaching skills
      required to promote disaster preparedness in their local communities. CURRICULUM
      DESIGN: The course consists of 2 weeks of classroom activities followed by 8
      weeks of e-learning structured within five domains of disaster medicine. The
      curriculum introduces core principles in emergency medicine, public health, and
      disaster management. Simulations, experiential activities, case studies, and role
      playing activities are all used to promote higher levels of cognitive engagement.
      Special content addresses the adult-learning process, and students design their
      own community-based seminars in disaster preparedness. CONCLUSIONS: The
      curriculum is designed to promote learning in disaster medicine. Given the
      paucity of disaster medicine educators in the region, student graduates of this
      program would be able to improve disaster preparedness in Saudi Arabia by
      launching their own community-based disaster preparedness initiatives. The
      program could also be adapted for use throughout the Middle East.

PMID- 26312496
TI  - Exposures and symptoms among workers after an offsite train derailment and vinyl
      chloride release.
AB  - OBJECTIVE: In 2012 in New Jersey, a train derailment resulted in the puncture of
      a tanker car carrying liquid vinyl chloride under pressure, and a resulting
      airborne vinyl chloride plume drifted onto the grounds of a nearby refinery. This
      report details the investigation of exposures and symptoms among refinery
      workers. DESIGN AND SETTING: The investigation team met with refinery workers to
      discuss their experience after the derailment and provided workers a self
      administered survey to document symptoms and worker responses during the
      incident. Associations among categorical variables and experiencing symptoms were
      evaluated using Fisher's exact test. PARTICIPANTS: Twenty-six of 155 (17 percent)
      workers present at the refinery or driving on the access road the date the spill
      occurred completed the survey. MAIN OUTCOME MEASURE(S): Any self-reported symptom
      following exposure from the vinyl chloride release. RESULTS: Fifteen workers (58
      percent) reported >=1 symptom, most commonly headache (12, 46 percent). Three (12
      percent) reported using respiratory protection. No differences in reporting
      symptoms were observed by location during the incident or by the building in
      which workers sheltered. Workers who moved from one shelter to another during the
      incident (ie, broke shelter) were more likely to report symptoms (Fisher's exact
      test, p=0.03); however, there are only limited data regarding vinyl chloride
      concentrations in shelters versus outside. CONCLUSIONS: Breaking shelter might
      result in greater exposures, and managers and health and safety officers of
      vulnerable facilities with limited physical access should consider developing
      robust shelter-in-place plans and alternate emergency egress plans. Workers
      should consider using respiratory protection if exiting a shelter is necessary
      during a chemical incident.

PMID- 26312497
TI  - The simultaneous death of seven people due to the detonation of an antipersonnel
      landmine at the land borders of the European Union during peacetime.
AB  - This incident concerns the simultaneous death of seven people as a result of the
      accidental triggering of an antipersonnel landmine during peacetime. The victims
      were illegal migrants who attempted to cross the Greek-Turkish border zone and
      accidentally entered a demarcated minefield. This incident is presented because
      of its rarity and highlights the devastating consequences of the residual mines
      on the European Union eastern frontiers in peacetime. It also showcases the
      difficulties and risks that arise during the identification process in illegal
      migration issues. The victims' positions at the moment of explosion are indicated
      by the detailed forensic examination and comparison of the injuries' anatomical
      dispersion and their severity. 

PMID- 26312498
TI  - Organophosphorus-Tellurium Chemistry: From Fundamentals to Applications.

PMID- 26312499
TI  - Correction to "A Molecular Ruthenium Electrocatalyst for the Reduction of Carbon
      Dioxide to CO and Formate".

PMID- 26312500
TI  - An ancient Pygo-dependent Wnt enhanceosome integrated by Chip/LDB-SSDP.
AB  - TCF/LEF factors are ancient context-dependent enhancer-binding proteins that are
      activated by beta-catenin following Wnt signaling. They control embryonic
      development and adult stem cell compartments, and their dysregulation often
      causes cancer. beta-catenin-dependent transcription relies on the NPF motif of
      Pygo proteins. Here, we use a proteomics approach to discover the Chip/LDB-SSDP
      (ChiLS) complex as the ligand specifically binding to NPF. ChiLS also recognizes
      NPF motifs in other nuclear factors including Runt/RUNX2 and Drosophila ARID1,
      and binds to Groucho/TLE. Studies of Wnt-responsive dTCF enhancers in the
      Drosophila embryonic midgut indicate how these factors interact to form the Wnt
      enhanceosome, primed for Wnt responses by Pygo. Together with previous evidence,
      our study indicates that ChiLS confers context-dependence on TCF/LEF by
      integrating multiple inputs from lineage and signal-responsive factors, including
      enhanceosome switch-off by Notch. Its pivotal function in embryos and stem cells
      explain why its integrity is crucial in the avoidance of cancer. 

PMID- 26312501
TI  - Noise-induced plasticity of KCNQ2/3 and HCN channels underlies vulnerability and
      resilience to tinnitus.
AB  - Vulnerability to noise-induced tinnitus is associated with increased spontaneous
      firing rate in dorsal cochlear nucleus principal neurons, fusiform cells. This
      hyperactivity is caused, at least in part, by decreased Kv7.2/3 (KCNQ2/3)
      potassium currents. However, the biophysical mechanisms underlying resilience to
      tinnitus, which is observed in noise-exposed mice that do not develop tinnitus
      (non-tinnitus mice), remain unknown. Our results show that noise exposure
      induces, on average, a reduction in KCNQ2/3 channel activity in fusiform cells in
      noise-exposed mice by 4 days after exposure. Tinnitus is developed in mice that
      do not compensate for this reduction within the next 3 days. Resilience to
      tinnitus is developed in mice that show a re-emergence of KCNQ2/3 channel
      activity and a reduction in HCN channel activity. Our results highlight KCNQ2/3
      and HCN channels as potential targets for designing novel therapeutics that may
      promote resilience to tinnitus. 

PMID- 26312502
TI  - Progerin reduces LAP2alpha-telomere association in Hutchinson-Gilford progeria.
AB  - Hutchinson-Gilford progeria (HGPS) is a premature ageing syndrome caused by a
      mutation in LMNA, resulting in a truncated form of lamin A called progerin.
      Progerin triggers loss of the heterochromatic marker H3K27me3, and premature
      senescence, which is prevented by telomerase. However, the mechanism how progerin
      causes disease remains unclear. Here, we describe an inducible cellular system to
      model HGPS and find that LAP2alpha (lamina-associated polypeptide-alpha)
      interacts with lamin A, while its interaction with progerin is significantly
      reduced. Super-resolution microscopy revealed that over 50% of telomeres localize
      to the lamina and that LAP2alpha association with telomeres is impaired in HGPS.
      This impaired interaction is central to HGPS since increasing LAP2alpha levels
      rescues progerin-induced proliferation defects and loss of H3K27me3, whereas
      lowering LAP2 levels exacerbates progerin-induced defects. These findings provide
      novel insights into the pathophysiology underlying HGPS, and how the nuclear
      lamina regulates proliferation and chromatin organization. 

PMID- 26312505
TI  - Plasmodium falciparum malaria occurring four years after leaving an endemic area.
AB  - We present a case of a 52-year-old woman of Ghanaian origin who developed
      Plasmodium falciparum malaria 4 years after leaving Africa. She had not returned
      to an endemic area since. We hypothesize several possible scenarios to explain
      this infection, of which we believe recrudescence of P. falciparum is the most
      plausible. This occurred most likely as a consequence of waning immunity several
      years after leaving a high-transmission area. She recovered after a 3-day
      treatment with atovaquone/proguanil. 

PMID- 26312503
TI  - NUDT21-spanning CNVs lead to neuropsychiatric disease and altered MeCP2 abundance
      via alternative polyadenylation.
AB  - The brain is sensitive to the dose of MeCP2 such that small fluctuations in
      protein quantity lead to neuropsychiatric disease. Despite the importance of
      MeCP2 levels to brain function, little is known about its regulation. In this
      study, we report eleven individuals with neuropsychiatric disease and copy-number
      variations spanning NUDT21, which encodes a subunit of pre-mRNA cleavage factor
      Im. Investigations of MECP2 mRNA and protein abundance in patient-derived
      lymphoblastoid cells from one NUDT21 deletion and three duplication cases show
      that NUDT21 regulates MeCP2 protein quantity. Elevated NUDT21 increases usage of
      the distal polyadenylation site in the MECP2 3' UTR, resulting in an enrichment
      of inefficiently translated long mRNA isoforms. Furthermore, normalization of
      NUDT21 via siRNA-mediated knockdown in duplication patient lymphoblasts restores
      MeCP2 to normal levels. Ultimately, we identify NUDT21 as a novel candidate for
      intellectual disability and neuropsychiatric disease, and elucidate a mechanism
      of pathogenesis by MeCP2 dysregulation via altered alternative polyadenylation. 

PMID- 26312506
TI  - The many sides of Research Integrity: For Integrity in Nursing!

PMID- 26312504
TI  - Inducible depletion of adult skeletal muscle stem cells impairs the regeneration
      of neuromuscular junctions.
AB  - Skeletal muscle maintenance depends on motor innervation at neuromuscular
      junctions (NMJs). Multiple mechanisms contribute to NMJ repair and maintenance;
      however muscle stem cells (satellite cells, SCs), are deemed to have little
      impact on these processes. Therefore, the applicability of SC studies to
      attenuate muscle loss due to NMJ deterioration as observed in neuromuscular
      diseases and aging is ambiguous. We employed mice with an inducible Cre, and
      conditionally expressed DTA to deplete or GFP to track SCs. We found SC depletion
      exacerbated muscle atrophy and type transitions connected to neuromuscular
      disruption. Also, elevated fibrosis and further declines in force generation were
      specific to SC depletion and neuromuscular disruption. Fate analysis revealed SC
      activity near regenerating NMJs. Moreover, SC depletion aggravated deficits in
      reinnervation and post-synaptic morphology at regenerating NMJs. Therefore, our
      results propose a mechanism whereby further NMJ and skeletal muscle decline
      ensues upon SC depletion and neuromuscular disruption. 

PMID- 26312507
TI  - Child Health Surveillance: nurses perspective.
AB  - OBJECTIVE: to analyze conceptions of nurses on child health surveillance in
      family health units. METHOD: a qualitative study with thematic analysis of the
      data, based on the paradigm of Health Surveillance. Interviews were conducted
      with 13 nurses in a countryside city in the state of Sao Paulo. RESULTS: nurses
      conceived child health surveillance as an active monitoring, which should be
      comprehensive, identifying risks/vulnerabilities, through multidisciplinary and
      intersectoral actions that are dependent on maternal involvement. We found
      partial development of these assumptions in practice, due to difficulties such as
      lack of maternal involvement in the proposed actions, lack of time for discussion
      and adoption of measures in the units and disarticulation between levels and
      sectors of the city. CONCLUSION: a greater political and technical investment is
      needed to ensure the adoption of this model in different sectors and levels of
      care of the city.

PMID- 26312508
TI  - Rescuing the pleasure of playing of child with cancer in a hospital setting.
AB  - OBJECTIVE: to dimension spaces and people that act on playing of children with
      cancer in outpatient treatment. METHOD: qualitative research developed with the
      creative sensitive method. A total of twenty two family members of seven children
      with cancer in outpatient treatment at a public hospital in Rio de Janeiro
      participated of this research. Data were generated in the family members' homes,
      from September 2011 to May 2012. RESULTS: after the diagnosis of childhood
      cancer, there was a change of scene and in the people who interact and play with
      children. Hospital has a central place for it, since children discover the
      pleasure of playing in this setting. CONCLUSION: the health care professional,
      especially nurses, who work on hospital care needs, should develop the ability of
      facilitate playing and therefore, enable care that promotes childhood
      development.

PMID- 26312509
TI  - From real to ideal--the health (un)care of long-lived elders.
AB  - OBJECTIVE: to analyze similarities and dissimilarities in the meanings assigned
      to health care by long-lived elders and nursing professionals in a healthcare
      setting. METHOD: ethnographic qualitative research, based on the Spradley-McCurdy
      method and the interpretive anthropology of Geertz and Kleinman. The sample
      consisted of 20 key informants. Data were collected through participatory
      observation and ethnographic interviews from March to October 2013 and analyzed
      in domains, taxonomies and cultural themes. RESULTS: Six domains and cultural
      taxonomies emerged and revealed reasons, attributes, and resources in providing
      care in relationship to long-lived elders and nursing professionals; finally, the
      following cultural theme emerged: the real to the ideal - the health (un)care of
      long-lived elders. CONCLUSION: The study showed the distance between the desired
      and actual health care provided to aged people in the scenario studied.

PMID- 26312510
TI  - Elderly families of South of Brazil in the Health Strategy.
AB  - OBJECTIVE: to characterize families and health status of the elderly in the
      Family Health Strategy and to verify the association of family composition with
      sociodemographic characteristics and health of the elderly. METHOD: population
      based study with 215 families and 266 elderly, linked to the Family Health
      Strategy from a city of Rio Grande do Sul state. RESULTS: there was predominance
      of nuclear family composition, considered as the main source of informal support,
      families of female elderly (62.6%) and cardiovascular complication. The nuclear
      structure was significantly associated with female gender (PR = 0.77; p = 0.025)
      and smoking (PR = 1.35; p = 0.009). CONCLUSION: the results reinforce the need to
      maintain a network of formal and informal support to the elderly and their
      families to preserve the independence or to postpone the decline in functional
      capacity.

PMID- 26312511
TI  - Study of billing audits in a teaching hospital.
AB  - OBJECTIVES: to determine which component items of hospital bills, examined by
      nurse auditors, were adjusted the most during pre-analysis; to identify the
      impact upon revenue caused by the adjustments to bills analyzed by physician and
      nurse auditors; and to identify disallowances related to items checked by the
      audit team. METHOD: quantitative, exploratory, descriptive, single-case study.
      RESULTS: after analysis of 2,613 bills, it was found that the item most included
      by nurses was gas (90.5%) and the most excluded was inpatient drugs (41.2%).
      Hemodynamics materials, gases and equipment had the greatest impact on upward
      adjustments. Downward adjustments were the result of improper entries on bills
      and did not generate revenue losses. Of total disallowances, 52.24% were related
      to the pre-analysis of nurses and 47.76% to that of physicians. CONCLUSION: this
      study of the pre-analysis process provides input that enhances knowledge about
      hospital bill audits.

PMID- 26312512
TI  - The Informal Caregiver Burden Assessment Questionnaire: validation for Brazil.
AB  - OBJECTIVES: to analyze the dimensionality, convergent construct validity and
      internal consistency of the Informal Caregiver Burden Assessment Questionnaire
      (QASCI) after its semantic adaptation to Brazil. METHOD: this methodological
      study was developed with 132 informal caregivers of elders who are dependent of
      help for basic or instrumental activities of daily living, in a capital city in
      Northeast Brazil. Quality of life measures related to health, anxiety and
      depression were used in the analysis of the convergent construct validity of the
      QASCI. RESULTS: the results of the instrument construct validation evidenced
      statistically significant correlations with the three measures. The confirmatory
      factor analysis evidenced good adjustment of the theoretical model of seven
      factors (domains) of the version used in the group studied. Cronbach's alpha for
      the scale total was 0.92. CONCLUSION: the Brazilian version of the QASCI was
      considered to be valid and reliable for assessing the burden of informal elder
      caregivers.

PMID- 26312513
TI  - AIDS epidemic in the triple frontier: subsidies for professional practice.
AB  - OBJECTIVE: to analyze the AIDS epidemic trend from 1988 to 2012, in a tri-border
      area. METHOD: Ecological time-series study with data from the Department of
      informatics from the Brazilian Unified Health System (SUS). RESULTS: A total of
      1427 cases of AIDS were registered, and 82.1% were aged 20-49 years and 56% in
      males. The relationship man/woman went from 9/1 to 1/1 and increased the number
      of cases among individuals with more years of education, also, people aged more
      than 50 years old the age group from 20 to 34 years old. The most common exposure
      category was heterosexual, significantly higher among women; on the other hand,
      drug injection use was associated with male gender. CONCLUSION: seeking to
      embrace the changes in the epidemiological scenario of AIDS, nursing
      professionals should implement intervention strategies for people identified as
      the most vulnerable to HIV infection.

PMID- 26312514
TI  - Potentialities and weaknesses in the care network of people with HIV/AIDS.
AB  - OBJECTIVE: to understand the strengths and weaknesses in the care network of
      people with HIV/AIDS in a referral center in the state of Santa Catarina-SC.
      METHOD: participants were eight subjects and their care network, totaling 18
      participants. Data were collected through interviews and examined by content
      analysis, theoretically supported by symbolic interaction. RESULTS: the analysis
      resulted in the following categories: The network offering care to people with
      acquired immunodeficiency syndrome, and Facing Barriers in care, which reflect
      the strengths and weaknesses in the care network. The fi rst depicts the
      provision of emotional and humanized care, and the second a restricted network
      formed by health professionals and a family member. CONCLUSION: the professional
      care network is important, despite the increased number of assistances in a
      physical structure and amount of professionals who no longer meet the growing
      demand.

PMID- 26312515
TI  - Instrument for evaluation of sedentary lifestyle in patients with high blood
      pressure.
AB  - OBJECTIVE: this article describes the diagnostic accuracy of the International
      Physical Activity Questionnaire to identify the nursing diagnosis of sedentary
      lifestyle. METHOD: a diagnostic accuracy study was developed with 240 individuals
      with established high blood pressure. The analysis of diagnostic accuracy was
      based on measures of sensitivity, specificity, predictive values, likelihood
      ratios, efficiency, diagnostic odds ratio, Youden index, and area under the
      receiver-operating characteristic curve. RESULTS: statistical differences between
      genders were observed for activities of moderate intensity and for total physical
      activity. Age was negatively correlated with activities of moderate intensity and
      total physical activity. CONCLUSION: the analysis of area under the receiver
      operating characteristic curve for moderate intensity activities, walking, and
      total physical activity showed that the International Physical Activity
      Questionnaire present moderate capacity to correctly classify individuals with
      and without sedentary lifestyle.

PMID- 26312516
TI  - Nursing Terminology defines domestic violence against children and adolescents.
AB  - OBJECTIVE: Identification of terminology relating to nursing practices aimed at
      children and adolescents at risk of domestic violence. METHODS: bibliographic
      descriptive research which selected 40 articles from the Virtual Health Library
      on domestic violence against children and adolescents, its manifestations,
      causes, and consequences, in association with nursing procedures for its
      confrontation and prevention, and which also identified terminology via computer
      tools. RESULTS: 17,365 terms that, after standardization and uniformity
      procedures, resulted in a listing of 915 terms. CONCLUSION: The terminology
      selected focused on the individual biopsychic nexus and the historic
      manifestation of this phenomenon was partially identified in terms that appear
      less frequently in these articles, thereby explaining the contradiction between
      the formal identification logic of such terminology and the dialectic logic that
      recognizes the historic reasons for, and dynamicity of, such phenomena.

PMID- 26312517
TI  - Workers of CEASA: factors associated with fatigue and work ability.
AB  - OBJECTIVE: to investigate the socio-demographic characteristics, lifestyle and
      health conditions related to fatigue and the work ability. METHOD: a cross
      sectional study was conducted in 2011 and the sample was composed by 90 workers
      from the supply center of Campinas. Three questionnaires were used: Fatigue; Work
      ability index; and socio-demographic characteristics. RESULTS: in the univariate
      regression analysis, the variables associated with work ability were: education,
      use of medicine, stress, pain in the last six months and pain in the last week.
      In univariate regression analysis the variables associated with fatigue were:
      education, stress, sleepiness, pain in the last six months, pain in the last week
      and health problems. CONCLUSION: these results indicate the need for health
      promotion program implementation among these workers.

PMID- 26312518
TI  - Gateway to the diagnosis of tuberculosis among elders in Brazilian
      municipalities.
AB  - OBJECTIVE: to analyze the factors associated with the gateway of the health
      systems of Brazilian municipalities for the diagnosis of tuberculosis in older
      people. METHOD: survey study type, with a sample of 91 elders, in a population
      with 706 cases of tuberculosis. Data were collected by means of an instrument
      based on the Primary Care Assessment Tool (PCAT) adapted for tuberculosis care,
      emphasizing the gateway variable. Variables were categorized and compared between
      primary health care (PHC) and specialized care (SC) services. Bivariate analysis
      and the Chi-square association test were used. RESULTS: a statistically
      significant association (p = 0.0001) was found between the fi rst health service
      sought and the unit that diagnosed tuberculosis, showing better performance of
      specialized care services in the diagnosis. CONCLUSION: it is necessary to
      improve primary health care services to tackle delayed diagnosis of tuberculosis
      in older people.

PMID- 26312519
TI  - Drug addicts treatment motivations: perception of family members.
AB  - OBJECTIVE: to identify the reasons and motivations why family members search
      treatment for the drug addicted. METHOD: descriptive qualitative research,
      developed in 2012 and 2013, in a Drug Addicts Rehabilitation Unit of Parana
      State, Brazil. A total of 19 semi-structured interviews were conducted with the
      drug addicts' family members in treatment. The results were analyzed based on the
      Transtheoretical Model of Behavior Change and organized in thematic categories
      according with qualitative data analysis. RESULTS: the search for treatment for
      drug addicts occurred: in the pre-contemplation stage influenced by external
      factors; in the contemplation stage both for ambivalence and behavioral changes
      needs; in the action stage by awareness of drug addiction and also professional
      help needs; and in the maintenance stage because of the non-conservation of
      behavioral changes. CONCLUSION: an evaluation of motivational stages in the
      beginning of treatment is required for expansion of success possibilities in the
      rehabilitation process.

PMID- 26312520
TI  - Health promotion in supplementary health care: outsourcing, microregulation and
      implications for care.
AB  - OBJECTIVE: to analyze health promotion programs in the supplementary health care.
      METHODS: This was a multiple case study with a qualitative approach whose data
      were obtained from interviews with coordinators of providers contracted by the
      corporations of health insurance plans in Belo Horizonte, Minas Gerais. The data
      were submitted to Critical Discourse Analysis. RESULTS: Home care has been
      described as the main action in the field of health promotion transferred to the
      providers, followed by management of patients and cases, and the health
      education.groups. The existence of health promotion principles is questionable in
      all programs. Outsourcing is marked by a process with a division between cost and
      care management. Implications of this process occur within admission and
      interventions on the needs of the beneficiaries. CONCLUSIONS: Statements revealed
      rationalization of cost, restructuring of work, and reproduction of the dominant
      logic of capital accumulation by the health insurance companies.

PMID- 26312521
TI  - Body language in health care: a contribution to nursing communication.
AB  - OBJECTIVE: to classify body language used in nursing care, and propose "Body
      language in nursing care" as an analytical category for nursing communication.
      METHOD: quantitative research with the systematic observation of 21:43 care
      situations, with 21 members representing the nursing teams of two hospitals.
      Empirical categories: sound, facial, eye and body expressions. RESULTS: sound
      expressions emphasized laughter. Facial expressions communicated satisfaction and
      happiness. Eye contact with members stood out in visual expressions. The most
      frequent body expressions were head movements and indistinct touches. CONCLUSION:
      nursing care team members use body language to establish rapport with patients,
      clarify their needs and plan care. The study classified body language
      characteristics of humanized care, which involves, in addition to technical, non
      technical issues arising from nursing communication.

PMID- 26312522
TI  - Nursing guidance on bed baths to reduce anxiety.
AB  - OBJECTIVE: to evaluate the effectiveness of a nursing guidance protocol to reduce
      the anxiety of patients with acute coronary syndrome undergoing bed bath, and the
      correlation of vital signs with state-anxiety. METHOD: randomized clinical trial
      study. The sample consisted of 120 patients. The intervention group received a
      nursing guidance protocol about bed bath and the control group received the
      unit's routine information. The STAI-State scale was used to assess anxiety, and
      data were collected at three times: immediately after informing the patients
      about the bed bath; immediately after interventions; and immediately after the
      bath. RESULTS: the intervention group presented significantly lower state-anxiety
      compared to the control group (p<0.001) after the intervention. CONCLUSION: the
      nursing orientation was effective to reduce anxiety in patients with acute
      coronary syndrome undergoing bed bath.

PMID- 26312523
TI  - Anxiety and spirituality in university students: a cross-sectional study.
AB  - OBJECTIVE: to study anxiety and spirituality and the relationship between them in
      university students. METHOD: the State-Trait-Anxiety Inventory (STAI) and Pinto
      and Pais-Ribeiro Spirituality Scales were used for data collection. RESULTS: six
      hundred and sixty-nine students participated in the study, of whom 91.5% had
      moderate and high levels of trait anxiety and 92.9% of state anxiety; 93.8% had
      high spirituality scores. The multiple linear regression test showed a
      significant relationship between anxiety and the presence of physical discomfort,
      unusual body movements, and the need for treatment. Furthermore, higher levels of
      anxiety were associated with the female gender, the lack of leisure activities,
      and low levels of optimism in the spirituality scale. CONCLUSION: it is important
      to develop strategies for coping with anxiety, which in turn can be oriented
      toward protective factors such as spirituality.

PMID- 26312524
TI  - Cognitive stimulation for older people with Alzheimer's disease performed by the
      caregiver.
AB  - OBJECTIVE: to learn the influence of cognitive therapy at home, conducted by the
      caregivers of older people with Alzheimer's Disease. METHOD: a case study was
      developed with fi ve older people with Alzheimer's Disease and their caregivers.
      The stages of research development were: orientation with the caregivers;
      selection of older people and caregivers; approach of the study subjects at home;
      weekly meetings and reapplication of tests to follow up the cognitive function of
      the participants. RESULTS: in three months it was possible to identify improved
      cognition, verified by the result of the Mini-Mental State Examination (MMSE).
      The scores of the other tests (KATZ, LAWTON, CLOCK TEST and VFT) remained the
      same. CONCLUSION: this strategy can be considered a light technology of nursing
      care for older people with dementia. When providing this care with the support of
      a nurse, caregivers re feel less anxious and understand the disease better.

PMID- 26312525
TI  - Perceptions of adolescent students about drugs.
AB  - OBJECTIVE: To analyze the perceptions of adolescent public school students about
      drugs. METHOD: Qualitative approach of focus groups with 16 adolescent students.
      The data collected were analyzed by means of content analysis, leading to the
      following categories: meaning of drugs; living with drug use; opinions, beliefs
      and attitudes toward drug use; and preventing drug abuse in adolescence. RESULTS:
      The adolescent students know about some drugs, and associate their use with
      delinquent and criminal behavior. The students identified factors that lead to
      drug abuse, such as easy access, use by family and friends, idleness, dropping
      out of school and the characteristic vulnerability of adolescence. CONCLUSION:
      the results point to the need for educational activities in the context of where
      the adolescents live, including school, community and family environments, to
      support and to minimize their vulnerability.

PMID- 26312526
TI  - Anticipated directives and living will for terminal patients: an integrative
      review.
AB  - OBJECTIVE: characterizing the national and international scientific literature
      about the advanced directives of living will as applied to the terminally ill
      patient. METHOD: integrative review considering the articles published in Portal
      Capes, SciELO, LILACS, MEDLINE, Journal of Bioethics and Bioethikos, with the
      descriptors: Advanced directives, Wills regarding life and Advance Directives,
      Living Will and Terminally Ill, totaling 44 articles submitted to content
      analysis. RESULTS: three categories emerged: Students and professionals facing
      the advance directives of living will: Perceptions, opinions and practices;
      Patient's receptivity to the Advance Directives of Living Will; The family facing
      the advance directives of living will. CONCLUSION: the relevance of the topic
      became evident as a guarantee of respect for the dignity and autonomy of the
      patient, as well as to reduce ethical conflicts faced by families and health
      professionals facing care at the end of life.

PMID- 26312528
TI  - Drosophila as a model to study the role of glia in neurodegeneration.
AB  - Neurons and glia interact reciprocally. Glia perform many important functions in
      the development and proper functioning of the nervous system throughout different
      stages of life. Neurons also affect the development and function of glia.
      Neurodegenerative diseases are usually late-onset, progressive, and affect
      specific parts of the nervous system. Many neurodegenerative disorders have been
      extensively studied. However, the majority of the studies have focused on the
      events that occur in neurons. The events that occur in glia, and whether and how
      glia participate in the pathogenesis of these diseases, have not been as well
      studied. In this review, we will focus on how the fruit fly Drosophila
      melanogaster has been used as a model to study neuron-glia interactions in
      neurodegenerative disorders. We discuss how glia are affected in these models of
      human neurodegenerative disorders and how glia contribute to their pathogenesis.
      These studies have provided important insight into the mechanisms of diverse
      neurodegenerative disorders, and have suggested possibilities for early
      diagnosis. 

PMID- 26312529
TI  - More responsive, less reactive.

PMID- 26312530
TI  - Dementia in palliative care: a new era for the hospice.

PMID- 26312527
TI  - Replication-induced DNA damage after PARP inhibition causes G2 delay, and cell
      line-dependent apoptosis, necrosis and multinucleation.
AB  - PARP inhibitors have been approved for treatment of tumors with mutations in or
      loss of BRCA1/2. The molecular mechanisms and particularly the cellular
      phenotypes resulting in synthetic lethality are not well understood and varying
      clinical responses have been observed. We have investigated the dose- and time
      dependency of cell growth, cell death and cell cycle traverse of 4 malignant
      lymphocyte cell lines treated with the PARP inhibitor Olaparib. PARP inhibition
      induced a severe growth inhibition in this cell line panel and increased the
      levels of phosphorylated H2AX-associated DNA damage in S phase. Repair of the
      remaining replication related damage caused a G2 phase delay before entry into
      mitosis. The G2 delay, and the growth inhibition, was more pronounced in the
      absence of functional ATM. Further, Olaparib treated Reh and Granta-519 cells
      died by apoptosis, while U698 and JVM-2 cells proceeded through mitosis with
      aberrant chromosomes, skipped cytokinesis, and eventually died by necrosis. The
      TP53-deficient U698 cells went through several rounds of DNA replication and
      mitosis without cytokinesis, ending up as multinucleated cells with DNA contents
      of up to 16c before dying. In summary, we report here for the first time cell
      cycle-resolved DNA damage induction, and cell line-dependent differences in the
      mode of cell death caused by PARP inhibition. 

PMID- 26312531
TI  - What do you want?

PMID- 26312532
TI  - Patient experience of non-malignant ascites and its treatment: a qualitative
      study.
AB  - BACKGROUND: Ascites is an accumulation of serous fluid in the abdominal cavity.
      It can be caused by both malignant and non-malignant conditions and produces
      distressing symptoms. There have been no qualitative studies looking at the
      experiences of patients with non-malignant ascites. AIMS: To explore the
      experiences of patients living with non-malignant ascites and its management.
      Also, to explore the views of these patients about services available to them.
      METHOD: Phenomenological qualitative research study using digitally recorded semi
      structured interviews. SETTING AND PARTICIPANTS: Six adult patients with non
      malignant ascites who were receiving paracentesis to manage their symptoms in an
      acute hospital day unit. RESULTS: Participants experienced a wide variety of
      physical symptoms. They discussed how the ascites impacted on their social lives.
      They had views on diuretics, low sodium diet and paracentesis as methods of
      symptom management. Participants' confidence in staff performing paracentesis was
      a common finding, particularly as ultrasound was rarely used. While only some
      were suitable for liver transplant, all discussed their future care needs.
      CONCLUSION: Participants' experiences of non-malignant ascites are that it has a
      considerable effect on their quality of life. Patients like the system of day
      case admission for drainage, but question whether this is sustainable. Advanced
      practitioners can successfully provide a paracentesis service for these patients
      in hospitals and potentially this is transferable to hospices. Patients seemed
      happy to consider the option of semi-permanent drains and pumps as methods of
      managing ascites.

PMID- 26312533
TI  - Neuropathic pain in people with cancer (part 2): pharmacological and non
      pharmacological management.
AB  - The aim of this paper is to provide an overview of the management of neuropathic
      pain associated with cancer and to provide helpful clinical advice for nurses
      working with patients who may have neuropathic pain. While cancer pain is a mixed
      mechanism pain, this article will focus only on neuropathic pain management. The
      impact of neuropathic pain on patients' quality of life is great and while many
      patients recover from their cancer, a significant number continue to suffer from
      a neuropathic pain syndrome. Management of neuropathic pain is significantly
      different from management of nociceptive pain with respect to pharmacological and
      non-pharmacological strategies. Neuropathic pain is complex, and as such requires
      complex management using pharmacological as well as non-pharmacological
      approaches. Specific drugs for neuropathic pain may be effective for some
      patients, but not all; therefore, ongoing and comprehensive assessment and
      management are required. Furthermore, these patients may require trials of
      several drugs before they find one that works for them. It is important for
      nurses to understand neuropathic pain, its manifestation, impact on quality of
      life and management when nursing patients with neuropathic pain associated with
      cancer. 

PMID- 26312534
TI  - A Japanese booklet about palliative care for advanced dementia in nursing homes.
AB  - BACKGROUND: A Canadian guide for nursing home staff on comfort care for dementia
      has been translated and adapted for use in Japan. The present study piloted
      educational intervention for nursing home staff using the Japanese comfort care
      booklet. METHOD: Some 61 nursing home staff (nurses and other care workers)
      completed a session that included pre-assessment, a 30-minute seminar using the
      comfort care booklet, post-assessment, and a one-hour debriefing meeting. A
      Japanese version of the questionnaire on palliative care for advanced dementia
      (qPAD) scale was used to assess knowledge and attitudes toward palliative care
      for advanced dementia. RESULTS: The participants demonstrated a significant
      increase in knowledge (mean score, 14.3 to 15.1/23, t (60) = 2.35, p=0.011) and
      attitudes (43.8 to 45.2/60, t (60) = 2.51, p = 0.015) toward palliative care for
      advanced dementia from pre-assessment to post-assessment. CONCLUSION: The
      educational intervention using the Japanese comfort care booklet may have
      improved nursing home staff's perspectives on palliative care for advanced
      dementia.

PMID- 26312535
TI  - The effect of a care bundle on nursing staff when caring for the dying.
AB  - BACKGROUND: Most Australians die in acute hospital settings. Despite this,
      hospitals remain ill-equipped to care for dying patients with hospital deaths not
      uncommonly perceived as distressing by both patients and their families. As a
      quality improvement project, a care bundle for the dying was developed and
      piloted on two medical wards. The aim of this study was to examine whether or not
      the quality initiative had any effect on the ward nurse's attitudes and self
      assessed competency to care for dying patients. METHODS: A pre- and post-survey
      using self-administered questionnaires were given to nursing staff who
      voluntarily completed these before and after implementation of the caring for the
      dying bundle. RESULTS: Over the 6 months the bundle was piloted, 74.5% of people
      who died did so with the bundle in place. While this was seen as clinically
      useful by nearly half the nurses who responded, there was not a significant
      change in the staff's attitudes or self-assessed competency to care for dying
      patients. There was a minor change in the Thanatophobia Scale (pre 18.2: SD+/-9.0
      versus post 16.8: SD 7.8; P=0.53), the Self-efficacy in Palliative Care Scale for
      communication (pre 47.4: SD +/-17.4 versus post 54.7:SD+/-17.9; P=0.11) and
      patient management respectively (pre 54.3: SD +/-12.9 versus 59.1: SD +/-12.6;
      P=0.15). DISCUSSION: This work highlighted that at least in the short term, that
      a quality initiative had only a modest impact on nursing attitudes to caring for
      dying patients. However, as a collection of clinical tools grouped as a care
      bundle, a proportion of nursing staff acknowledged this initiative as useful.
      CONCLUSION: Further research is required to understand if such an initiative
      approach may, in the long term, positively impacts attitude. This is highly
      relevant given the increasing numbers of people likely to die in acute care.

PMID- 26312536
TI  - Palliative care in dementia: literature review of nurses' knowledge and attitudes
      towards pain assessment.
AB  - BACKGROUND: Pain is prevalent among older people, yet is often under-recognised
      and undertreated in people with dementia. The nurse has a central role in
      identifying and appropriately assessing pain in order to provide effective
      treatment. Research however suggests there are significant deficits in this area.
      AIM: To explore the evidence on nurses' knowledge and attitudes to pain
      assessment in older people with dementia. DESIGN: A systematic narrative review
      of peer-reviewed articles published between 2000 and 2014. DATA SOURCES: Seven
      electronic data bases (CINAHL, MEDLINE, PsycInfo, Wiley, Pubmed, ProQuest and
      OVID) were searched and articles focusing on nurses knowledge and attitudes on
      pain assessment towards people with dementia. METHODS: Research participants
      within the studies reviewed were to include registered nurses involved in the
      assessment and management of pain in older adults with dementia from across all
      healthcare settings (e.g. dementia units, nursing homes, community and acute
      settings). RESULTS: Data were systematically analysed from 11 papers. Using an
      inductive approach for thematic content analysis informed by the theory of
      planned behaviour, five themes were identified. These included: 1) Challenges in
      diagnosing pain in dementia 2) Inadequacies of pain assessment tools 3) Time
      constraints and workload pressures 4) Lack of interdisciplinary teamwork and
      communication 5) Training and education. CONCLUSION: Nurses play a key role in
      the effective management of pain through the use of pain assessment tools,
      behavioural observation, and analgesic choice. Pain assessment in dementia
      remains challenging for nurses due to the complexity and individualisation of
      pain behaviours. The accessibility of appropriate training, workforce stability
      and a standardised approach to pain assessment are key to the successful
      management of pain in older people with dementia.

PMID- 26312537
TI  - 'Do I have to have cancer to get better care?' Improving palliative care
      provision for frail older people.

PMID- 26312538
TI  - Research roundup.
AB  - Synopses of a selection of recently published research articles of relevance to
      palliative care. 

PMID- 26312539
TI  - Politics and palliative care: Antigua and Barbuda.
AB  - Dion Smyth's review of the internet for palliative nursing. 

PMID- 26312541
TI  - Laparoscopic Duhamel Procedure for Hirschsprung's Disease: Systematic Review and
      Meta-analysis.
AB  - INTRODUCTION: Since its introduction in 1956, the Duhamel procedure has been and
      remains one of the most widely performed for Hirschsprung's disease (HD). The
      most significant modification to this procedure has been the incorporation of
      laparoscopy, while the original principles of the method have been retained. This
      study compared long-term outcomes for open Duhamel (OD) and laparoscopic Duhamel
      (LD) procedures for HD, to identify any added advantage of the laparoscopic
      technique. MATERIALS AND METHODS: We undertook a systematic review of all studies
      published over a period of 20 years (1994-2014) that assessed functional outcomes
      for OD and/or LD procedures. Odds ratios were calculated for dichotomous
      variables, and mean difference values were calculated for continuous variables.
      RESULTS: From 11 articles 456 patients were included (253 OD, 203 LD), with no
      significant difference in age at surgery and length of follow-up (P > .05). The
      open group had a significantly greater incidence of soiling/incontinence (11%
      versus 4%; P = .02) and further surgery (25% versus 14%; P = .005), longer
      hospital stay (9.79 versus 7.3 days; P < .00001), and time to oral feed (4.05
      versus 3.27 days; P < .00001). Operative time was significantly longer in the
      laparoscopic group (3.83 versus 4.09 hours; P = .004). There was no significant
      difference in incidence of enterocolitis (15% versus 10%; P = .14) and
      constipation (23% versus 30%; P = .12). CONCLUSIONS: Our meta-analysis
      convincingly demonstrates the superiority of LD over OD pull-through for HD.
      Prospective, randomized control trials are required to overcome limitations in
      the current literature.

PMID- 26312540
TI  - Serological proteome analysis reveals new specific biases in the IgM and IgG
      autoantibody repertoires in autoimmune polyendocrine syndrome type 1.
AB  - OBJECTIVE: Autoimmune polyendocrine syndrome type 1 (APS 1) is caused by
      mutations in the AIRE gene that induce intrathymic T-cell tolerance breakdown,
      which results in tissue-specific autoimmune diseases. DESIGN: To evaluate the
      effect of a well-defined T-cell repertoire impairment on humoral self-reactive
      fingerprints, comparative serum self-IgG and self-IgM reactivities were analyzed
      using both one- and two-dimensional western blotting approaches against a broad
      spectrum of peripheral tissue antigens. METHODS: Autoantibody patterns of APS 1
      patients were compared with those of subjects affected by other autoimmune
      endocrinopathies (OAE) and healthy controls. RESULTS: Using a Chi-square test,
      significant changes in the Ab repertoire were found when intergroup patterns were
      compared. A singular distortion of both serum self-IgG and self-IgM repertoires
      was noted in APS 1 patients. The molecular characterization of these antigenic
      targets was conducted using a proteomic approach. In this context, autoantibodies
      recognized more significantly either tissue-specific antigens, such as pancreatic
      amylase, pancreatic triacylglycerol lipase and pancreatic regenerating protein
      1alpha, or widely distributed antigens, such as peroxiredoxin-2, heat shock
      cognate 71-kDa protein and aldose reductase. As expected, a well-defined self
      reactive T-cell repertoire impairment, as described in APS 1 patients, affected
      the tissue-specific self-IgG repertoire. Interestingly, discriminant IgM
      reactivities targeting both tissue-specific and more widely expressed antigens
      were also specifically observed in APS 1 patients. Using recombinant targets, we
      observed that post translational modifications of these specific antigens
      impacted upon their recognition. CONCLUSIONS: The data suggest that T-cell
      dependent but also T-cell-independent mechanisms are involved in the dynamic
      evolution of autoimmunity in APS 1.

PMID- 26312542
TI  - Current treatment recommendations and considerations for cryopyrin-associated
      periodic syndrome.
AB  - Cryopyrin-associated periodic syndrome (CAPS) encompasses a spectrum of three
      phenotypes of increasing severity. The syndrome is due to dominant mutations in
      NLRP3, which encodes a key component of the innate immunity that regulates the
      secretion of IL-1beta. CAPS manifests as systemic inflammation, which compromises
      quality of life and leads to serious complications and handicap. Anti-IL-1 drugs
      have shown remarkable efficacy in treating CAPS symptoms and have significantly
      changed patients' lives. They have acceptable safety profiles but do have some
      differences. We review three drugs that are currently marketed for CAPS, give
      additional information for the practical use of these drugs, and provide some
      recommendations for management. 

PMID- 26312543
TI  - High prevalence of cardiovascular co-morbidities in patients with symptomatic
      knee or hand osteoarthritis.
AB  - OBJECTIVES: To evaluate the frequency of cardiovascular events (CVEs) and
      metabolic syndrome (MetS) in patients with symptomatic knee or hand
      osteoarthritis (OA). METHOD: A cross-sectional study conducted by rheumatologists
      in a primary care setting. Consecutive symptomatic patients with primary knee or
      hand OA were included and patients with soft tissue conditions served as the
      control group. Hypertension, diabetes mellitus, obesity, dyslipidaemia, and CVEs
      consisting of myocardial infarction, angina, or cerebrovascular disease were
      recorded. RESULTS: A total of 254 OA patients (184 with knee OA and 70 with hand
      OA) and 254 control patients were included. The frequency of obesity was higher
      in all OA groups and hypertension was more frequent in knee OA. MetS was
      significantly more frequent in patients with OA as a whole group and in knee or
      hand OA groups separately (p < 0.001, p = 0.002, and p = 0.007, respectively, vs.
      control group), with odds ratio (OR) 2.4, 95% confidence interval (CI) 1.26-4.55
      in the OA group, OR 2.29, 95% CI 1.15-4.54 in the knee OA group, and OR 2.67, 95%
      CI 1.15-6.19 in the hand OA group. A higher prevalence of CVEs in the three OA
      groups was observed compared with the control group. CONCLUSIONS: A high
      frequency of MetS and CVEs was observed in OA patients in a primary care setting.

PMID- 26312544
TI  - Association between 25(OH)-vitamin D and testosterone levels: Evidence from men
      with chronic spinal cord injury.
AB  - OBJECTIVE: As an independent linear association between 25-hydroxyvitamin D
      (25(OH)D) and testosterone levels is controversial, this study aimed to explore
      this topic in men with chronic spinal cord injury (SCI), who exhibit a high
      prevalence of both androgen and vitamin D deficiency. DESIGN: Forty-nine men with
      chronic SCI consecutively admitted to a rehabilitation program underwent
      clinical/biochemical evaluations. RESULTS: Deficiency of 25(OH)D (<20 ng/mL) was
      found in 36 patients (73.5%). They exhibited significantly lower total
      testosterone and free testosterone levels, higher parathyroid hormone (PTH) and
      HOMA-IR, a poorer functional independence degree, and were engaged in poorer
      weekly leisure time physical activity (LTPA). Significant correlates of 25(OH)D
      levels were: total testosterone, free testosterone, PTH, functional independence
      degree and weekly LTPA. At the linear regression models, lower 25(OH)D levels
      were associated with both lower total and free testosterone after adjustment for
      age, smoking, alcohol consumption, comorbidities and HOMA-IR. However, after full
      adjustment, also including functional independence degree, BMI and LTPA, only the
      association of lower 25(OH)D with lower free testosterone was still significant.
      CONCLUSION: In men with SCI, 25(OH)D correlates with total and free testosterone
      and exhibits an independent linear association with free testosterone. Regardless
      of this independent link, hypovitaminosis D and androgen deficiency are markers
      of poor health, sharing common risk factors to take into account in the
      rehabilitative approach to patients with SCI.

PMID- 26312545
TI  - Wheezes and desert breezes: when asthma and valley fever collide.
AB  - OBJECTIVE: To evaluate interactive effects of pulmonary coccidioidomycosis and
      asthma. METHODS: We identified three groups of 33 age- and sex-matched patients:
      Group 1 (both asthma and coccidioidomycosis), Group 2 (asthma only), and Group 3
      (pulmonary coccidioidomycosis only). Predetermined end points included: rate of
      disseminated coccidioidomycosis, duration of symptoms and antifungal therapy,
      hospitalization, death, and escalation of asthma therapies. RESULTS: Baseline
      characteristics were similar across groups. Group 1 patients had worsening asthma
      outcomes (except forced expiratory volume in 1 s) with coccidioidomycosis. They
      required more asthma medications (median, 2.0 vs 0.0; p < 0.001), more
      corticosteroids (mean [SD], 0.9 [4.2] vs 0.3 [0.6]; p < 0.001), and more
      healthcare visits (mean [SD], 0.2 [0.4] vs 0.1 [0.3]; p = 0.03). Groups 1 and 3
      had no differences in coccidioidal end points, including rates of dissemination
      (1 vs 0; p > 0.99), symptom duration (mean, 15.2 vs 23.6 weeks; p = 0.24),
      antifungal treatment (n = 21 [63.6%] vs n = 24 [72.7%]; p = 0.60), and treatment
      duration (median, 26.5 vs 11 weeks; p = 0.09). Ten patients in Group 1 versus
      none in Group 3 required systemic corticosteroids for coccidioidomycosis (p <
      0.001). CONCLUSIONS: Active pulmonary coccidioidomycosis significantly worsens
      asthma outcomes. Asthma (or its treatment) does not worsen coccidioidal outcomes,
      despite increasing the likelihood of treatment with systemic corticosteroids.

PMID- 26312546
TI  - Presidential Address: My Time with the Parasites.

PMID- 26312547
TI  - Discontinuation of anticoagulant treatment: from clinical trials to medication
      persistence.
AB  - BACKGROUND: The new generation, non-vitamin K antagonist oral anticoagulants are
      used in an increasing frequency, partially replacing the vitamin K antagonists in
      several fields of anticoagulation. Efficacy of the preventive oral anticoagulant
      regime, however, may be compromised by patient non-compliance. METHODS: The
      authors analyzed treatment discontinuation frequencies in phase 3 trials of
      anticoagulant treatment in non-valvular atrial fibrillation in a frequentist
      random effect metaanalysis and in Bayesian multiple treatment network comparison.
      RESULTS: Frequency of discontinuations are heterogeneous and highly inconsistent
      (Chi2 test for heterogeneity p < 0.001, I2 test for inconsistency 95.1%).
      Discontinuations were the most frequent with dabigatran followed by rivaroxaban,
      warfarin, edoxaban and apixaban. Rivaroxaban were less frequently discontinued
      when compared to the two doses of dabigatran. (OR 0.80; 95% CI: 0.71-0.91 versus
      150 mg b.i.d., and OR: 0.77; 95% CI: 0.68-0.87 versus 110 mg b.i.d.). CONCLUSION:
      Important differences exist among the treatment adherence of different
      anticoagulant protocols. Discontinuation rates experienced during the clinical
      trials may predict the real life patient adherence.

PMID- 26312548
TI  - Relationship of creatine kinase to body composition, disease state, and longevity
      in ALS.
AB  - Our objective was to explore if creatine kinase (CK) levels correlate with
      survival in amyotrophic lateral sclerosis (ALS), and whether a correlation is
      independent of other well-studied predictors such as location of onset, gender,
      age, fat free mass, spasticity, cramps, and fasciculations. We analyzed data from
      80 ALS patients from a 48-week non-interventional longitudinal multicenter
      nutrition study with long term follow-up. The overall mean CK was 214 +/- 191.8
      U/l (range 22-1992 U/l). Forty-five percent of patients had at least one high CK
      value (> 200 U/l), and about half maintained a high CK value, but there was no
      trend over the study period. Male gender and extremity onset were significantly
      associated with high CK. In univariate analysis, age, bioelectric impedance
      spectroscopy (BIS) fat free mass, spasticity, and fasciculations were not
      associated with CK level. There was an association between CK and muscle cramps
      (p < 0.001). In survival analysis, low CK (<= 200 U/l) was associated with a
      longer overall survival (p = 0.02), when adjusting for location of onset, age,
      race, gender, BIS fat free mass, and study site. In conclusion, CK may be a
      useful marker for ALS survival, which has implications for clinical care and the
      design of future clinical trials. 

PMID- 26312550
TI  - Age, Creatinine and Ejection Fraction Score in Brazil: Comparison with InsCor and
      the EuroSCORE.
AB  - BACKGROUND: Risk scores for cardiac surgery cannot continue to be neglected.
      OBJECTIVE: To assess the performance of "Age, Creatinine and Ejection Fraction
      Score" (ACEF Score) to predict mortality in patients submitted to elective
      coronary artery bypass graft and/or heart valve surgery, and to compare it to
      other scores. METHODS: A prospective cohort study was carried out with the
      database of a Brazilian tertiary care center. A total of 2,565 patients submitted
      to elective surgeries between May 2007 and July 2009 were assessed. For a more
      detailed analysis, the ACEF Score performance was compared to the InsCor's and
      EuroSCORE's performance through correlation, calibration and discrimination
      tests. RESULTS: Patients were stratified into mild, moderate and severe for all
      models. Calibration was inadequate for ACEF Score (p = 0.046) and adequate for
      InsCor (p = 0.460) and EuroSCORE (p = 0.750). As for discrimination, the area
      under the ROC curve was questionable for the ACEF Score (0.625) and adequate for
      InsCor (0.744) and EuroSCORE (0.763). CONCLUSION: Although simple to use and
      practical, the ACEF Score, unlike InsCor and EuroSCORE, was not accurate for
      predicting mortality in patients submitted to elective coronary artery bypass
      graft and/or heart valve surgery in a Brazilian tertiary care center.

PMID- 26312549
TI  - AUTEN-67, an autophagy-enhancing drug candidate with potent antiaging and
      neuroprotective effects.
AB  - Autophagy is a major molecular mechanism that eliminates cellular damage in
      eukaryotic organisms. Basal levels of autophagy are required for maintaining
      cellular homeostasis and functioning. Defects in the autophagic process are
      implicated in the development of various age-dependent pathologies including
      cancer and neurodegenerative diseases, as well as in accelerated aging. Genetic
      activation of autophagy has been shown to retard the accumulation of damaged
      cytoplasmic constituents, delay the incidence of age-dependent diseases, and
      extend life span in genetic models. This implies that autophagy serves as a
      therapeutic target in treating such pathologies. Although several autophagy
      inducing chemical agents have been identified, the majority of them operate
      upstream of the core autophagic process, thereby exerting undesired side effects.
      Here, we screened a small-molecule library for specific inhibitors of MTMR14, a
      myotubularin-related phosphatase antagonizing the formation of autophagic
      membrane structures, and isolated AUTEN-67 (autophagy enhancer-67) that
      significantly increases autophagic flux in cell lines and in vivo models. AUTEN
      67 promotes longevity and protects neurons from undergoing stress-induced cell
      death. It also restores nesting behavior in a murine model of Alzheimer disease,
      without apparent side effects. Thus, AUTEN-67 is a potent drug candidate for
      treating autophagy-related diseases. 

PMID- 26312551
TI  - Assessment of Galectin-3 Polymorphism in Subjects with Chronic Chagas Disease.
AB  - BACKGROUND: Galectin-3, a beta-galactoside binding lectin, has been described as
      a mediator of cardiac fibrosis in experimental studies and as a risk factor
      associated with cardiovascular events in subjects with heart failure. Previous
      studies have evaluated the genetic susceptibility to Chagas disease in humans,
      including the polymorphisms of cytokine genes, demonstrating correlations between
      the genetic polymorphism and cardiomyopathy development in the chronic phase.
      However, the relationship between the galectin-3 single nucleotide polymorphism
      (SNP) and phenotypic variations in Chagas disease has not been evaluated.
      OBJECTIVE: The present study aimed to determine whether genetic polymorphisms of
      galectin-3 may predispose to the development of cardiac forms of Chagas disease.
      METHODS: Fifty-five subjects with Chagas disease were enrolled in this
      observational study. Real-time polymerase chain reaction (PCR) was used for
      genotyping the variants rs4644 and rs4652 of the galectin-3 gene. RESULTS: For
      the SNP rs4644, the relative risk for the cardiac form was not associated with
      the genotypes AA (OR = 0.79, p = 0.759), AC (OR = 4.38, p = 0.058), or CC (OR =
      0.39, p = 0.127). Similarly, for the SNP rs4652, no association was found between
      the genotypes AA (OR = 0.64, p = 0.571), AC (OR = 2.85, p = 0.105), or CC (OR =
      0.49, p = 0.227) and the cardiac form of the disease. CONCLUSION: Our results
      showed no association between the different genotypes for both SNPs of the
      galectin-3 gene and the cardiac form of Chagas disease.

PMID- 26312552
TI  - Efficacy of Patient Selection for Diagnostic Coronary Angiography in Suspected
      Coronary Artery Disease.
AB  - BACKGROUND: Guidelines recommend that in suspected stable coronary artery disease
      (CAD), a clinical (non-invasive) evaluation should be performed before coronary
      angiography. OBJECTIVE: We assessed the efficacy of patient selection for
      coronary angiography in suspected stable CAD. METHODS: We prospectively selected
      consecutive patients without known CAD, referred to a high-volume tertiary
      center. Demographic characteristics, risk factors, symptoms and non-invasive test
      results were correlated to the presence of obstructive CAD. We estimated the CAD
      probability based on available clinical data and the incremental diagnostic value
      of previous non-invasive tests. RESULTS: A total of 830 patients were included;
      median age was 61 years, 49.3% were males, 81% had hypertension and 35.5% were
      diabetics. Non-invasive tests were performed in 64.8% of the patients. At
      coronary angiography, 23.8% of the patients had obstructive CAD. The independent
      predictors for obstructive CAD were: male gender (odds ratio [OR], 3.95;
      confidence interval [CI] 95%, 2.70 - 5.77), age (OR for 5 years increment, 1.15;
      CI 95%, 1.06 - 1.26), diabetes (OR, 2.01; CI 95%, 1.40 - 2.90), dyslipidemia (OR,
      2.02; CI 95%, 1.32 - 3.07), typical angina (OR, 2.92; CI 95%, 1.77 - 4.83) and
      previous non-invasive test (OR 1.54; CI 95% 1.05 - 2.27). CONCLUSIONS: In this
      study, less than a quarter of the patients referred for coronary angiography with
      suspected CAD had the diagnosis confirmed. A better clinical and non-invasive
      assessment is necessary, to improve the efficacy of patient selection for
      coronary angiography.

PMID- 26312553
TI  - Adsorbing a PVDF polymer via noncovalent interactions to effectively tune the
      electronic and magnetic properties of zigzag SiC nanoribbons.
AB  - On the basis of first-principle computations, we first propose a simple and
      effective strategy through surface-adsorbing a poly(vinylidene fluoride) (PVDF)
      polymer via noncovalent interactions to tune the electronic and magnetic
      behaviors of zigzag SiC nanoribbons (zSiCNRs). It is revealed that depositing the
      strong electron-withdrawing PVDF polymer with a permanent dipole moment can
      induce the evident change of the electrostatic potential in the substrate
      zSiCNRs, like applying an electric field. As a result, this kind of noncovalent
      surface-modification by a polymer can break the magnetic degeneracy of zSiCNRs
      independent of the adsorption type and position, and sole ferromagnetic
      metallicity and even antiferromagnetic half-metallicity can be achieved.
      Moreover, all PVDF-modified zSiCNR systems can exhibit considerable adsorption
      energies in the range of -0.436 to -1.315 eV, indicating that these joint systems
      possess high structural stabilities. These intriguing findings will be
      advantageous for promoting excellent SiC-based nanomaterials in the applications
      of spintronics and multifunctional nanodevices in the near future. 

PMID- 26312554
TI  - Constraining Data Mining with Physical Models: Voltage- and Oxygen Pressure
      Dependent Transport in Multiferroic Nanostructures.
AB  - Development of new generation electronic devices necessitates understanding and
      controlling the electronic transport in ferroic, magnetic, and optical materials,
      which is hampered by two factors. First, the complications of working at the
      nanoscale, where interfaces, grain boundaries, defects, and so forth, dictate the
      macroscopic characteristics. Second, the convolution of the response signals
      stemming from the fact that several physical processes may be activated
      simultaneously. Here, we present a method of solving these challenges via a
      combination of atomic force microscopy and data mining analysis techniques.
      Rational selection of the latter allows application of physical constraints and
      enables direct interpretation of the statistically significant behaviors in the
      framework of the chosen physical model, thus distilling physical meaning out of
      raw data. We demonstrate our approach with an example of deconvolution of complex
      transport behavior in a bismuth ferrite-cobalt ferrite nanocomposite in ambient
      and ultrahigh vacuum environments. Measured signal is apportioned into four
      electronic transport patterns, showing different dependence on partial oxygen and
      water vapor pressure. These patterns are described in terms of Ohmic conductance
      and Schottky emission models in the light of surface electrochemistry.
      Furthermore, deep data analysis allows extraction of local dopant concentrations
      and barrier heights empowering our understanding of the underlying dynamic
      mechanisms of resistive switching. 

PMID- 26312555
TI  - New Butyrolactone Type Lignans from Arctii Fructus and Their Anti-inflammatory
      Activities.
AB  - Arctiidilactone (1), a novel rare butyrolactone lignan with a 6-carboxyl-2-pyrone
      moiety, and 11 new butyrolactone lignans (2-12) were isolated from the fruits of
      Arctium lappa L., together with 5 known compounds (13-17). Their structures were
      elucidated by interpretation of their spectroscopic data (1D and 2D NMR, UV, IR,
      ORD, and HRESIMS) and comparison to literature data. The absolute configurations
      of compounds 1-12 were determined by a combination of rotating-frame nuclear
      Overhauser effect spectroscopy (ROESY), circular dichroism (CD) spectroscopy, and
      Rh2(OCOCF3)4-induced CD spectroscopy. All of the compounds were tested for their
      anti-inflammatory properties in terms of suppressing the production of NO in
      lipopolysaccharide-induced BV2 cells. Compounds 1, 6, 8, and 10 exhibited
      stronger anti-inflammatory effects than the positive control curcumin,
      particularly 1, which exhibited 75.51, 70.72, and 61.17% inhibition at 10, 1, and
      0.1 MUM, respectively. 

PMID- 26312556
TI  - Analysis of Metrics for Molecular Sonotransfer in Vitro.
AB  - Ultrasound induced microbubble (MB) cavitation is used to significantly enhance
      cell membrane permeabilization, thereby allowing delivery of various therapeutic
      agents into cells. In order to monitor and quantitatively control the extent of
      cavitation the uniform dosimetry model is needed. In present study we have
      simultaneously performed quantitative evaluation of three main sonoporation
      factors: (1) MB concentration, (2) MB cavitation extent, and (3) doxorubicin
      (DOX) sonotransfer into Chinese hamster ovary cells. MB concentration measurement
      results and passively recorded MB cavitation signals were used for MB
      sonodestruction rate and spectral root-mean-square (RMS) calculations,
      respectively. Subsequently, time to maximum value of RMS and inertial cavitation
      dose (ICD) quantifications were performed for every acoustic pressure value. This
      comprehensive research has led not only to explanation of relation of ICD and MB
      sonodestruction rate but also to the development of a new sonoporation metric:
      the inverse of time to maximum value of RMS (1/time to maximum value of RMS). ICD
      and MB sonodestruction rate intercorrelation and correlation with DOX
      sonotransfer suggest inertial cavitation to be the key mechanism for cell
      sonoporation. All these metrics were successfully used for doxorubicin
      sonotransfer prediction (R(2) > 0.9, p < 0.01) and therefore shows feasibility to
      be applied for future dosimetric applications for ultrasound-mediated drug and
      gene delivery. 

PMID- 26312557
TI  - In Situ FT-IR Spectroscopic Studies of CO Adsorption on Fresh Mo2C/Al2O3
      Catalyst.
AB  - The surface sites of supported molybdenum carbide catalyst derived from different
      synthesis stages have been studied by in situ FT-IR spectroscopy using CO as the
      probe molecule. Adsorbed CO on the reduced passivated Mo2C/Al2O3 catalyst gives a
      main band at 2180 cm(-1), which can be assigned to linearly adsorbed CO on Mo(4+)
      sites. The IR results show that the surface of reduced passivated sample is
      dominated by molybdenum oxycarbide. However, a characteristic IR band at 2054 cm(
      1) was observed for the adsorbed CO on MoO3/Al2O3 carburized with CH4/H2 mixture
      at 1033 K (fresh Mo2C/Al2O3), which can be assigned to linearly adsorbed CO on
      Mo(delta+) (0 < delta < 2) sites of Mo2C/Al2O3. Unlike adsorbed CO on reduced
      passivated Mo2C/Al2O3 catalyst, the IR spectra of adsorbed CO on fresh Mo2C/Al2O3
      shows similarity to that on some of the group VIII metals (such as Pt and Pd),
      suggesting that fresh carbide resembles noble metals. To study the stability of
      Mo2C catalyst during H2 treatment and find proper conditions to remove the
      deposited carbon species, H2 treatment of fresh Mo2C/Al2O3 catalyst at different
      temperatures was conducted. Partial amounts of carbon atoms in Mo2C along with
      some surface-deposited carbon species can be removed by the H2 treatment even at
      450 K. Both the surface-deposited carbon species and carbon atoms in carbide can
      be extensively removed at temperatures above 873 K. 

PMID- 26312558
TI  - A Comprehensive Proteomics Analysis Reveals a Secretory Path- and Status
      Dependent Signature of Exosomes Released from Tumor-Associated Macrophages.
AB  - Exosomes are 30-120 nm-sized membrane vesicles of endocytic origin that are
      released into the extracellular environment and play roles in cell-cell
      communication. Tumor-associated macrophages (TAMs) are important constituents of
      the tumor microenvironment; thus, it is critical to study the features and
      complex biological functions of TAM-derived exosomes. Here, we constructed a TAM
      cell model from a mouse macrophage cell line, Ana-1, and performed comparative
      proteomics on exosomes, exosome-free media, and cells between TAMs and Ana-1.
      Proteomic analysis between exosome and exosome-free fractions indicated that the
      functions of exosome dominant proteins were mainly enriched in RNA processing and
      proteolysis. TAM status dramatically affected the abundances of 20S proteasome
      subunits and ribosomal proteins in their exosomes. The 20S proteasome activity
      assay strongly indicated that TAM exosomes possessed higher proteolytic activity.
      In addition, Ana-1- and TAM-derived exosomes have different RNA profiles, which
      may result from differential RNA processing proteins. Taken together, our
      comprehensive proteomics study provides novel views for understanding the
      complicated roles of macrophage-derived exosomes in the tumor microenvironment. 

PMID- 26312559
TI  - Highly Enhanced Gas Adsorption Properties in Vertically Aligned MoS2 Layers.
AB  - In this work, we demonstrate that gas adsorption is significantly higher in edge
      sites of vertically aligned MoS2 compared to that of the conventional basal plane
      exposed MoS2 films. To compare the effect of the alignment of MoS2 on the gas
      adsorption properties, we synthesized three distinct MoS2 films with different
      alignment directions ((1) horizontally aligned MoS2 (basal plane exposed), (2)
      mixture of horizontally aligned MoS2 and vertically aligned layers (basal and
      edge exposed), and (3) vertically aligned MoS2 (edge exposed)) by using rapid
      sulfurization method of CVD process. Vertically aligned MoS2 film shows about 5
      fold enhanced sensitivity to NO2 gas molecules compared to horizontally aligned
      MoS2 film. Vertically aligned MoS2 has superior resistance variation compared to
      horizontally aligned MoS2 even with same surface area exposed to identical
      concentration of gas molecules. We found that electrical response to target gas
      molecules correlates directly with the density of the exposed edge sites of MoS2
      due to high adsorption of gas molecules onto edge sites of vertically aligned
      MoS2. Density functional theory (DFT) calculations corroborate the experimental
      results as stronger NO2 binding energies are computed for multiple configurations
      near the edge sites of MoS2, which verifies that electrical response to target
      gas molecules (NO2) correlates directly with the density of the exposed edge
      sites of MoS2 due to high adsorption of gas molecules onto edge sites of
      vertically aligned MoS2. We believe that this observation extends to other 2D TMD
      materials as well as MoS2 and can be applied to significantly enhance the gas
      sensor performance in these materials. 

PMID- 26312560
TI  - Antiwetting Fabric Produced by a Combination of Layer-by-Layer Assembly and
      Electrophoretic Deposition of Hydrophobic Nanoparticles.
AB  - This work describes a nanoparticle coating method to produce durable antiwetting
      polyester fabric. Electrophoretic deposition is used for fast modification of
      polyester fabric with silica nanoparticles embedded in polymeric networks for
      high durability coatings. Typically, electrophoretic deposition (EPD) is utilized
      on electrically conductive substrates due to its dependence on an applied
      electrical field. EPD on nonconductive materials has been attempted but are
      limited by weak adhesion, cracks, and other irregularities. To resolve these
      issues, we coat polyester fabric with thin polymer layers using electrostatic
      self-assembly (layer-by-layer self-assembly). Next, silica nanoparticles are
      uniformly dispersed on the polymer layers. Finally, polymerically stabilized
      silica nanoparticles are deposited by EPD on the fabric, followed by heat
      treatment. The modified fabric shows high static contact angle and low contact
      angle hysteresis, while keeping its original color, flexibility, and air
      permeability. During a skin fiction resistance test, the hydrophobicity of the
      coating layer was maintained over 500 h. Furthermore, we also show that this
      approach facilitates patterned regions of wettability by modifying the electric
      field in EPD. 

PMID- 26312561
TI  - Correction: Resolving the anomalous infrared spectrum of the MeCN-HCl molecular
      cluster using ab Initio molecular dynamics.
AB  - Correction for 'Resolving the anomalous infrared spectrum of the MeCN-HCl
      molecular cluster using ab Initio molecular dynamics' by Nicolai Bork et al.,
      Phys. Chem. Chem. Phys., 2014, 16, 24685-24690. 

PMID- 26312565
TI  - LOX-1 boosts immunity.

PMID- 26312566
TI  - Regulation of T follicular helper cells by ICOS.

PMID- 26312567
TI  - A Hrd way for MHC-II expression.

PMID- 26312562
TI  - Dual enzyme-responsive "turn-on" fluorescence sensing systems based on in situ
      formation of 7-hydroxy-2-iminocoumarin scaffolds.
AB  - A new strategy for the simultaneous fluorogenic detection of two distinct enzyme
      activities namely hydrolase (amidase or esterase) and reductase is described.
      This innovative biosensing method is based on the powerful "covalent-assembly"
      principle that involves in situ synthesis of a fluorophore from a non-fluorescent
      caged precursor and through domino reactions triggered by the two analytes of
      interest. To establish this approach, penicillin G acylase (PGA) (or pig liver
      esterase (PLE)) and nitroreductase (NTR) were chosen as model enzymes, and
      original bis-O-protected 2,4-dihydroxycinnamonitrile derivatives acting as dual
      reactive probes readily convertible to highly fluorescent 7-hydroxy-2
      iminocoumarin scaffolds upon reacting with the two selected enzymes were
      synthesised. The two phenolic groups available within the core structure of these
      probes play a pivotal role in generating iminocoumarin scaffold through an
      intramolecular cyclisation reaction (hydroxyl group in C-2 position) and in
      enhancing its push-pull character (hydroxyl group in C-4 position). Their
      orthogonal and temporary protection with two different enzyme-labile masking
      groups is the cornerstone in the design of this novel class of fluorogenic "turn
      on" probes. Their evaluation using fluorescence-based in vitro assays and HPLC
      fluorescence/-MS analyses have enabled us both to demonstrate the claimed
      activation mechanism (in particular the specific order in which the two enzymes
      react with the probe) and to highlight the potential utility of these advanced
      chemical tools in multi-analyte sensing applications. 

PMID- 26312563
TI  - Significance of S100P as a biomarker in diagnosis, prognosis and therapy of
      opisthorchiasis-associated cholangiocarcinoma.
AB  - Cholangiocarcinoma (CCA) is a malignancy of bile duct with the difficulty in
      early diagnosis, poor prognosis and less alternation in therapy. S100P is a
      member of S100 family proteins and plays important roles in cancers. We
      investigated the S100P expression and its correlation with clinicopathology in 78
      cases of opisthorchiasis-associated CCA, and the effects of S100P knockdown with
      shRNA interference on the proliferation, cell cycle, migration, apoptosis and
      sensitivity to anti-cancer drug. Extremely high expression of S100P mRNA was
      detected in the CCA tumor tissues. The increased S100P protein expression was
      immunohistochemically confirmed and localized in the CCA cytoplasm and/or nuclei
      as well as in the hyperneoplasia and dysplasia bile ducts, but not in normal bile
      ducts. The intensity of immunostaining was correlated with survival, tumor stage
      and metastasis, and the high expression could be an independent prognostic
      factor. High levels of S100P were detected in the serum and bile fluid of CCA
      patients. The shRNA-mediated knockdown of S100P expression inhibited the
      proliferation in vitro and in vivo, and migration of CCA cells, arrested cell
      cycle with the up-regulated expression of cell cycle arrest related factors, p21,
      p27, GADD45A, and 14-3-3 zeta. S100P knockdown also promoted CCA cell apoptosis
      by up-regulating expression of apoptosis related factors, DR5, TRADD, caspase 3
      and BAX, and increased the sensitivity of CCA cells to the chemotherapeutic
      agents sunitinib and apigenin. Taken together, this study indicates that S100P
      might be a promising biomarker for the diagnosis, prognosis and therapy of CCA. 

PMID- 26312568
TI  - NIR light-directing self-organized 3D photonic superstructures loaded with
      anisotropic plasmonic hybrid nanorods.
AB  - Self-organized 3D photonic superstructures loaded with plasmonic hybrid nanorods
      were found to undergo structural transformation from body-centered cubic to
      simple cubic upon NIR-light irradiation resulting from the "photothermal effect"
      of gold nanorods. Furthermore, dynamic NIR light-directed red, green and blue
      reflections of the nanocomposites were demonstrated. 

PMID- 26312564
TI  - CCDC34 is up-regulated in bladder cancer and regulates bladder cancer cell
      proliferation, apoptosis and migration.
AB  - The coiled coil is a superhelical structural protein motif involved in a diverse
      array of biological functions, and the abnormal expression of the coiled-coil
      domain containing proteins has a direct link with the phenotype of tumor cell
      migration, invasion and metastasis. The aim of this study was to investigate the
      critical role of Coiled-coil domain-containing protein 34 (CCDC34) in bladder
      carcinogenesis, which has never been reported to date. Here, we found CCDC34
      expression was elevated in bladder cancer tissues and cell lines. The knockdown
      of CCDC34 via lentivirus-mediated siRNA significantly suppressed bladder cancer
      cells proliferation and migration, and induced cell cycle arrest at G2/M phase
      and increased apoptosis in vitro. In addition, CCDC34 knockdown suppressed
      bladder tumor growth in nude mice. Moreover, CCDC34 silencing decreased the
      phosphorylation of MEK, ERK1/2, JNK, p38 and Akt, and the expressions of c-Raf
      and c-Jun, indicating MAPK and AKT pathways (ERK/MAPK, p38/MAPK, JNK/MAPK and
      PI3K/Akt) might be involved in CCDC34 regulation of bladder cancer cell
      proliferation and migration. Our findings revealed for the first time a potential
      oncogenic role for CCDC34 in bladder carcinoma pathogenesis and it may serve as a
      biomarker or even a therapeutic target for bladder cancer. 

PMID- 26312569
TI  - Morphology-Dependent Electrochemical Properties of CuS Hierarchical
      Superstructures.
AB  - Hierarchical superstructures formed by self-assembled nanoparticles exhibit
      interesting electrochemical properties that can potentially be exploited in Li
      ion batteries (LIBs) as possible electrode materials. In this work, we tested two
      different morphologies of CuS superstructures for electrodes, namely, tubular
      dandelion-like and ball-like assemblies, both of which are composed of similar
      small covellite nanoparticles. These two CuS morphologies are characterized by
      their markedly different electrochemical performances, suggesting that their
      complex structures/morphologies influence the electrochemical properties. At 1.12
      A g(-1), the cells made with CuS tubular structures delivered about 420 mAh g(
      1), and at 0.56 A g(-1), the capacity was as high as about 500 mAh g(-1) with
      good capacity retention. Their ease of preparation and processing, together with
      good electrochemical performance, make CuS tubular dandelion-like clusters
      attractive for developing low-cost LIBs based on conversion reactions.

PMID- 26312570
TI  - A Highly Stable and Magnetically Recyclable Nanocatalyst System: Mesoporous
      Silica Spheres Embedded with FeCo/Graphitic Shell Magnetic Nanoparticles and Pt
      Nanocatalysts.
AB  - We have developed a highly stable and magnetically recyclable nanocatalyst system
      for alkene hydrogenation. The materials are composed of mesoporous silica spheres
      (MSS) embedded with FeCo/graphitic shell (FeCo/GC) magnetic nanoparticles and Pt
      nanocatalysts (Pt-FeCo/GC@MSS). The Pt-FeCo/GC@MSS have superparamagnetism at
      room temperature and show type IV isotherm typical for mesoporous silica, thereby
      ensuring a large enough inner space (surface area of 235.3 m(2)  g(-1), pore
      volume of 0.165 cm(3)  g(-1), and pore diameter of 2.8 nm) to undergo catalytic
      reactions. We have shown that the Pt-FeCo/GC@MSS system readily converts
      cyclohexene into cyclohexane, which is the only product isolated and Pt
      FeCo/GC@MSS can be seperated very quickly by an external magnetic field after the
      catalytic reaction is finished. We have demonstrated that the recycled Pt
      FeCo/GC@MSS can be reused further for the same hydrogenation reaction at least
      four times without loss in the initial catalytic activity.

PMID- 26312571
TI  - A Catalog of Genetic Syndromes in Childhood Cancer.
AB  - Genetic syndromes and pediatric cancers are rare, so instances of co-occurrence
      raise the question of whether the two conditions may be etiologically linked.
      Clear examples of causal association can be found in the cancer predisposition
      syndromes. This report contains the results of a systematic literature search
      using Ovid Medline for co-occurrence of genetic syndromes with 23 types of
      pediatric cancer. The results reflect known associations as well as many reports
      of infrequently observed co-occurrences. This compilation may suggest previously
      overlooked patterns, and the information could be used to identify gene pathways
      critical in the development of childhood cancers.

PMID- 26312572
TI  - D-Root: a system for cultivating plants with the roots in darkness or under
      different light conditions.
AB  - In nature roots grow in the dark and away from light (negative phototropism).
      However, most current research in root biology has been carried out with the root
      system grown in the presence of light. Here, we have engineered a device, called
      Dark-Root (D-Root), to grow plants in vitro with the aerial part exposed to the
      normal light/dark photoperiod while the roots are in the dark or exposed to
      specific wavelengths or light intensities. D-Root provides an efficient system
      for cultivating a large number of seedlings and easily characterizing root
      architecture in the dark. At the morphological level, root illumination shortens
      root length and promotes early emergence of lateral roots, therefore inducing
      expansion of the root system. Surprisingly, root illumination also affects shoot
      development, including flowering time. Our analyses also show that root
      illumination alters the proper response to hormones or abiotic stress (e.g. salt
      or osmotic stress) and nutrient starvation, enhancing inhibition of root growth.
      In conclusion, D-Root provides a growing system closer to the natural one for
      assaying Arabidopsis plants, and therefore its use will contribute to a better
      understanding of the mechanisms involved in root development, hormonal signaling
      and stress responses. 

PMID- 26312573
TI  - Prevalence of and Risk Factors for Elder Abuse and Neglect in the Community: A
      Population-Based Study.
AB  - OBJECTIVES: To estimate past-year prevalence and identify risk and protective
      factors of elder emotional abuse, physical abuse, and neglect. DESIGN: Cross
      sectional, population-based study using random-digit-dial sampling and direct
      telephone interviews. SETTING: New York State households. PARTICIPANTS:
      Representative (race, ethnicity, sex) sample (N = 4,156) of English- or Spanish
      speaking, community-dwelling, cognitively intact individuals aged 60 and older.
      MEASUREMENTS: The Conflict Tactics Scale was adapted to assess elder emotional
      and physical abuse. Elder neglect was evaluated according to failure of a
      responsible caregiver to meet an older adult's needs using the Duke Older
      Americans Resources and Services (OARS) scale. Caseness thresholds were based on
      mistreatment behavior frequencies and elder perceptions of problem seriousness.
      RESULTS: Past-year prevalence of elder emotional abuse was 1.9%, of physical
      abuse was 1.8%, and of neglect was 1.8%, with an aggregate prevalence of 4.6%.
      Emotional and physical abuse were associated with being separated or divorced,
      living in a lower-income household, functional impairment, and younger age.
      Neglect was associated with poor health, being separated or divorced, living
      below the poverty line, and younger age. Neglect was less likely in older adults
      of Hispanic ethnicity. CONCLUSION: Elder abuse and neglect are common problems,
      with divergent risk and protective factor profiles. These findings have direct
      implications for public screening and education and awareness efforts designed to
      prevent elder mistreatment.

PMID- 26312574
TI  - Proposal of a new diagnostic algorithm for hepatocellular carcinoma based on the
      Japanese guidelines but adapted to the Western world for patients under
      surveillance for chronic liver disease.
AB  - To date, despite many scientific evidences, the guidelines of the principal
      hepatological societies, such as the American Association for the Study of Liver
      Diseases, the European Association for the Study of the Liver, and the Asian
      Pacific Association for the Study of the Liver, do not recognize the diagnostic
      superiority of magnetic resonance imaging (MRI) over computed tomography in the
      diagnosis of hepatocellular carcinoma (HCC) and, for the most part, do not
      contemplate the use of hepatospecific contrast media, such as gadolinium
      ethoxybenzyl-diethylenetriamine pentaacetic acid (EOB). The aim of this paper was
      to analyze the recent results of EOB-MRI in the study of chronic liver disease
      and the differences between the American Association for the Study of Liver
      Diseases and the Japan Society of Hepatology guidelines, of which the latter
      represents the most consolidated experience on EOB-MRI use for HCC diagnosis.
      Finally, a new diagnostic algorithm for HCC in patients under surveillance for
      chronic liver disease was formulated, which contemplates the use of EOB. This new
      diagnostic algorithm is based on the Japan Society of Hepatology algorithm but
      goes beyond it by adapting it to the Western world, taking into account both the
      difference between the two and the latest results concerning the diagnosis of
      HCC. This new diagnostic algorithm for HCC is proposed in order to provide useful
      diagnostic tools to all those Western countries where the use of EOB (more
      expensive than extracellular contrast media) is widespread but in which common
      strategies to manage the nodules that this new contrast agent allows identifying
      have not been available to date.

PMID- 26312575
TI  - Nitrogen-Nitrogen Bonds Undermine Stability of N-Doped Graphene.
AB  - Two-dimensional alloys of carbon and nitrogen draw strong interest due to
      prospective applications in nanomechanical and optoelectronic devices. The
      stability of these chemical structures can vary greatly as a function of chemical
      composition and structure. The present study employs hybrid density functional
      theory and reactive molecular dynamics simulations to elucidate how many nitrogen
      atoms can be incorporated into the graphene sheet without destroying it. We
      conclude that (1) the C/N = 56:29 structure and all nitrogen-poorer structures
      maintain stability at 1000 K; (2) the stability suffers greatly in the presence
      of N-N bonds; and (3) distribution of electron density depends heavily on the
      structural pattern in the N-doped graphene. Our calculations support the
      experimental efforts aimed at production of highly N-doped graphene and generate
      important insights into the mechanisms of tuning graphene mechanical and
      optoelectronic properties. The theoretical prediction can be tested directly by
      chemical synthesis. 

PMID- 26312576
TI  - Effect of Growth Hormone Treatment on Fractures and Quality of Life in
      Postmenopausal Osteoporosis: A 10-Year Follow-Up Study.
AB  - CONTEXT: Growth hormone (GH) treatment increases bone mineral density (BMD) in
      women with postmenopausal osteoporosis. OBJECTIVE: The objective was to report
      bone data, fractures, and quality of life (QoL) in a 10-year follow-up of women
      who had received GH for 3 years and compared with controls followed in parallel.
      DESIGN AND SETTING: A follow-up of a double-blind, placebo-controlled study
      conducted at Sahlgrenska University Hospital was performed. PATIENTS: Eighty
      women aged between 50 and 70 years with osteoporosis and estrogen hormone
      replacement were studied and compared with an age-matched random population
      sample of women (n = 120) from the World Health Organization Monitoring of Trends
      and Determinants in Cardiovascular Disease project (Gothenburg, Sweden).
      INTERVENTIONS: Patients were randomized to GH 1.0 U or GH 2.5 U recombinant human
      GH or placebo sc daily during 3 years. All received calcium 750 mg and vitamin D
      400 U and were followed up during 10 years. MAIN OUTCOME MEASURES: BMD and bone
      mineral content were measured with dual-energy X-ray absorptiometry. QoL was
      estimated with the 36-item Short Form. RESULTS: GH increased BMD and bone mineral
      content dose dependently in all regions (P = .01, GH 1.0 U, and P = .0006, GH 2.5
      U vs placebo). After 10 years the number of fractures decreased from 56% to 28%
      (P = .0003) in patients evenly distributed between groups. In controls, fractures
      increased from 8% to 32% (P = .0008). QoL did not change during GH treatment or
      during the 10-year follow-up and did not differ compared with controls.
      CONCLUSION: GH treatment was beneficial for bone and fracture outcome after 10
      years but did not affect the QoL of the women with postmenopausal osteoporosis.

PMID- 26312577
TI  - Bivariate Genome-Wide Association Study Implicates ATP6V1G1 as a Novel
      Pleiotropic Locus Underlying Osteoporosis and Age at Menarche.
AB  - OBJECTIVE: Age at menarche (AAM) is determined by the overall duration of
      endocrine-tissue sex hormone exposure levels. Osteoporosis, the most common
      metabolic bone disease, is characterized primarily by reduced bone mineral
      density (BMD) and an increased risk of low trauma fractures. Bone was an
      endocrine organ regulating the synthesis and secretion of sex steroid hormones.
      The mutual dependence between bone and gonads underscore the importance of
      genetic approaches to identify novel pleiotropic genetic factors coregulating BMD
      and AAM. In this study, we performed a bivariate genome-wide association study
      (GWAS) to explore novel ethnic common loci and/or genes that may influence both
      AAM and BMD. METHODS: We analyzed genotyping data available for 826 unrelated
      Chinese subjects using genome-wide human genotyping arrays. After quality
      control, a total of 702 413 single-nucleotide polymorphisms (SNPs) were tested
      for association using a bivariate linear regression model. The interesting SNPs
      were replicated in three independent cohorts including 1728 unrelated Caucasians,
      709 African-Americans, and 408 Hispanic-Americans. RESULTS: We found four SNPs
      (rs10817638, rs7851259, rs10982287, and rs4979427), located upstream of the
      ATP6V1G1 gene, were bivariately associated with hip BMD-AAM (P = 4.90 * 10(-7), P
      = 1.07 * 10(-6), P = 1.28 * 10(-5), and P = 5.42 * 10(-5), respectively). These
      four SNPs were replicated in African-Americans, with corresponding values of P =
      1.95 * 10(-2), P = 3.18 * 10(-2), P = 2.57 * 10(-2), and P = 3.64 * 10(-2),
      respectively. rs10817638 and rs10982287 were further replicated in Caucasians (P
      = 1.76 * 10(-2) and P = 9.42 * 10(-3), respectively) and Hispanic-Americans (P =
      8.37 * 10(-3) and P = 1.52 * 10(-3), respectively). Meta-analyses yielded
      stronger association signals for rs10817638 and rs10982287 with combined values
      of P = 3.02 * 10(-9) and P = 3.49 * 10(-9), respectively. CONCLUSIONS: Our study
      implicated ATP6V1G1 as a novel pleiotropic gene underlying variation of both BMD
      and AAM. The findings enhance our knowledge of genetic associations between BMD
      and AAM and provide a rationale for subsequent functional studies of these
      implicated genes in the pathophysiology of diseases/traits, such as osteoporosis
      and AAM.

PMID- 26312578
TI  - Selective Arterial Calcium Stimulation With Hepatic Venous Sampling
      Differentiates Insulinoma From Nesidioblastosis.
AB  - CONTEXT: In adult patients with endogenous hyperinsulinemic hypoglycemia and
      negative or inconclusive noninvasive imaging, insulinoma and non-insulinoma
      pancreatogenous hypoglycemic syndrome (NIPHS) resulting from diffuse
      nesidioblastosis must be considered in the differential diagnosis. It is not
      known whether the biochemical results of selective arterial calcium stimulation
      (SACST) with hepatic venous sampling can differentiate insulinoma from diffuse
      nesidioblastosis. OBJECTIVE: To determine the specificity of SACST with hepatic
      venous sampling in differentiating insulinoma from diffuse nesidioblastosis.
      DESIGN: Retrospective review (January 1996 to March 2014). SETTING: Tertiary
      referral center. PATIENTS OR OTHER PARTICIPANTS: A total of 116 patients with
      biochemical evidence of endogenous hyperinsulinemic hypoglycemia and negative or
      inconclusive noninvasive imaging who were subsequently shown at surgery to have
      insulinoma (n = 42) or nesidioblastosis (n = 74) after undergoing SACST with
      hepatic venous sampling. INTERVENTION(S): SACST with hepatic venous sampling
      before pancreatic exploration. MAIN OUTCOME MEASURE(S): Receiver operating
      characteristic curves were generated from the biochemical results of SACST to
      determine the specificity of the maximum hepatic venous insulin concentration
      (mHVI) and the relative-fold increase in hepatic venous insulin concentration
      (rHVI) over baseline after calcium injection from the dominant artery in
      differentiating insulinoma from nesidioblastosis. RESULTS: The mHVI (21.5-fold; P
      < .001) and rHVI (3.9-fold; P < .001) were significantly higher in the insulinoma
      group compared to the nesidioblastosis group. The areas under the receiver
      operating characteristic curve for mHVI and rHVI were excellent (0.94; P < .0001)
      and good (0.83; P < .0001), respectively, for differentiating insulinoma from
      nesidioblastosis. mHVI cutoffs of > 91.5 and > 263.5 MUIU/mL were 95 and 100%
      specific for insulinoma, respectively. A 19-fold increase in rHVI over baseline
      was 99% specific for insulinoma. CONCLUSIONS: These data suggest that the mHVI
      and rHVI at SACST may be useful in differentiating insulinoma from
      nesidioblastosis with high specificity in patients with hyperinsulinemic
      hypoglycemia and negative or inconclusive noninvasive imaging.

PMID- 26312579
TI  - Increased Body Mass Index in Parent-Child Dyads Predicts the Offspring Risk of
      Meeting Bariatric Surgery Criteria.
AB  - CONTEXT: Obesity in children is a major public health concern. OBJECTIVE: This
      study examined the value of using parent-child dyads' adiposity status for
      predicting the individual's later eligibility for bariatric surgery (EBS).
      DESIGN, SETTING, AND PARTICIPANTS: The cohort consisted of 2647 individuals from
      the longitudinal Cardiovascular Risk in Young Finns Study. Baseline information
      included own and parental body mass index (BMI) in 1980 (children aged 3-18
      years), whereas adult follow-up assessment examined EBS 21-31 years later. MAIN
      OUTCOME MEASURE: EBS in adulthood was defined as: 1) BMI greater than 40 kg/m(2)
      or 2) BMI greater than 35 kg/m(2) with at least one of the following metabolic
      complications: type 2 diabetes, hypertension, or dyslipidemia. RESULTS: Addition
      of parents' BMI improved the prediction of adulthood EBS compared to the model
      including child's BMI, age, and sex (area under the curve values [95% confidence
      interval] (0.80 [0.74-0.85] vs 0.74 [0.68-0.81], P = .003). Obese children with
      an obese parent had a 21.2% chance of being EBS in adulthood. Compared to
      nonobese families, the risk ratio for EBS was 14.2 (95% confidence interval 8.0
      25.2, P < .001) in obese children with an obese parent. The absolute risk of EBS
      was 30.9% if both child and parent were obese on more than one childhood
      assessment compared to 15.2% if they were obese only once, or 2.1% if they were
      never obese (P < .05). CONCLUSIONS: These longitudinal data show that a
      combination of the child's and parents' BMI at baseline assessment is a useful
      predictive tool for assessing later EBS, and highlights the importance of
      accounting for parental BMI in the assessment of child obesity.

PMID- 26312580
TI  - Free 25(OH)D and Calcium Absorption, PTH, and Markers of Bone Turnover.
AB  - CONTEXT: It has been proposed that serum free 25-hydroxyvitamin D [25(OH)D] may
      better reflect vitamin D action than total 25(OH)D. An ELISA for serum free
      25(OH)D has recently become available, permitting direct assay. OBJECTIVE: To
      determine whether serum free 25(OH)D provides additional information in relation
      to calcium absorption and other biomarkers of vitamin D action compared to total
      serum 25(OH)D. SETTING: Ambulatory research setting in a teaching hospital.
      OUTCOME: Serum free 25(OH)D measured in a previously performed study of varied
      doses of vitamin D3 (placebo and 800, 2000, and 4000 IU) on calcium absorption,
      PTH, procollagen type 1 N-terminal propeptide, and C-terminal telopeptides of
      type I collagen. Free 25(OH)D was measured by ELISA. Calcium absorption was
      measured at baseline and at 10 weeks using stable dual calcium isotopes. RESULTS:
      Seventy-one subjects completed this randomized, placebo-controlled trial.
      Baseline group mean free and total 25(OH)D varied from 4.7 +/- 1.8 to 5.4 +/- 1.5
      pg/mL, and from 23.7 +/- 5.9 to 25.9 +/- 6.1 ng/mL, respectively. Participants
      assigned to the 4000-IU dose arm achieved free 25(OH)D levels of 10.4 pg/mL and
      total 25(OH)D levels of 40.4 ng/mL. Total and free 25(OH)D were highly correlated
      at baseline and after increasing vitamin D dosing (r = 0.80 and 0.85,
      respectively). Free 25(OH)D closely reflected changes in total 25(OH)D. PTH was
      similarly correlated at baseline and follow-up with total and free 25(OH)D. Serum
      C-terminal telopeptides of type I collagen had a moderate positive correlation
      with total and free 25(OH)D at follow-up. The serum 1,25-dihydroxyvitamin D
      change increased significantly with the change in 25(OH)D but not with the change
      in free 25(OH)D. CONCLUSION: There was no advantage from measuring free over
      total 25(OH)D in assessing the response of calcium absorption, PTH, and markers
      of bone turnover to vitamin D. Free 25(OH)D responded to increasing doses of
      vitamin D in a similar fashion to total 25(OH)D.

PMID- 26312581
TI  - Use of Antibiotics and Risk of Type 2 Diabetes: A Population-Based Case-Control
      Study.
AB  - CONTEXT AND OBJECTIVE: Evidence that bacteria in the human gut may influence
      nutrient metabolism is accumulating. We investigated whether use of antibiotics
      influences the risk of developing type 2 diabetes and whether the effect can be
      attributed to specific types of antibiotics. METHODS: We conducted a population
      based case-control study of incident type 2 diabetes cases in Denmark (population
      5.6 million) between January 1, 2000, and December 31, 2012. Data from the Danish
      National Registry of Patients, the Danish National Prescription Registry, and the
      Danish Person Registry were combined. RESULTS: The odds ratio (OR) associating
      type 2 diabetes with exposure to antibiotics of any type was 1.53 (95% confidence
      interval 1.50-1.55) with redemption of more than or equal to 5 versus 0-1
      prescriptions. Although no individual group of antibiotics was specifically
      associated with type 2 diabetes risk, slightly higher ORs for type 2 diabetes
      were seen with narrow-spectrum and bactericidal antibiotics (OR 1.55 and 1.48)
      compared to broad-spectrum and bacteriostatic types of antibiotics (OR 1.31 and
      1.39), respectively. A clear dose-response effect was seen with increasing
      cumulative load of antibiotics. The increased use of antibiotics in patients with
      type 2 diabetes was found up to 15 years before diagnosis of type 2 diabetes as
      well as after the diagnosis. CONCLUSIONS: Our results could support the
      possibility that antibiotics exposure increases type 2 diabetes risk. However,
      the findings may also represent an increased demand for antibiotics from
      increased risk of infections in patients with yet-undiagnosed diabetes.

PMID- 26312583
TI  - The Moderating Role of Age in Responses to Direct-to-Consumer Prescription Drug
      Advertising.
AB  - Age is an important factor that can influence processing of and response to
      health messages. Many studies examining evaluations of and responses to direct-to
      consumer prescription drug advertising (DTCA) have incorporated age as a
      predictor variable, moderating variable, or sample criterion. However, findings
      have been inconsistent. This study attempts to add clarity to this body of
      research by assessing age differences in the antecedent factors of various DTCA
      outcomes. A multigroup structural equation modeling analysis revealed several
      significant differences in variable relationships between older (50+) and younger
      (<50) adults. Overall, older adults exhibited greater complexity in their
      consideration of DTCA than younger adults in terms of the sheer number of
      significant relationships within the model. In particular, trust in mediated
      health information sources and trust in one's physician appeared to be more
      relevant predictors for older adults. Trust in DTCA was also distinguished as
      having an inverse relationship with behavioral intentions among older adults
      while showing a straightforward positive association with attention among younger
      adults. Further analysis indicated that health status accounted for some but not
      all of the age differences. It is suggested that younger adults are more open to
      seeking additional information following DTCA exposure, whereas older adults
      remain ambivalent. 

PMID- 26312582
TI  - Effects of Interrupting Children's Sedentary Behaviors With Activity on Metabolic
      Function: A Randomized Trial.
AB  - CONTEXT: Limited data suggest that interrupting sedentary behaviors with activity
      improves metabolic parameters in adults. OBJECTIVE: We tested whether
      interrupting sitting with short, moderate-intensity walking bouts improved
      glucose tolerance in children. DESIGN: Participants underwent two experimental
      conditions in random order on different days: continuous sitting for 3 hours or
      sitting interrupted by walking (3 min of moderate-intensity walking every 30
      min). Insulin, C-peptide, glucose, and free fatty acids were measured every 30
      minutes for 3 hours during an oral glucose tolerance test. Area under the curve
      (AUC) was calculated from hormone and substrate measurements. Children were given
      a buffet meal after each condition. SETTING: The study was conducted at the
      National Institutes of Health Hatfield Clinical Research Center. PARTICIPANTS:
      Twenty-eight normal-weight 7-11 year olds participated. MAIN OUTCOMES: Patterns
      of substrate/hormone secretion and AUC, as well as energy intake, were examined
      by experimental condition. RESULTS: Interrupting sitting resulted in a 32% lower
      insulin AUC (P < .001), 17% lower C-peptide AUC (P < .001), and 7% lower glucose
      AUC (P = .018) vs continuous sitting. Mixed model results indicated that insulin
      (P = .036) and free fatty acid concentrations (P = .009) were significantly lower
      in the interrupted vs the continuous sitting condition. Lunchtime buffet meal
      energy intake did not significantly differ between the conditions (975 +/- 387 vs
      963 +/- 309 kcal; P = .85). CONCLUSIONS: Interrupting sedentary time with brief
      moderate-intensity walking improved short-term metabolic function in non
      overweight children without increasing subsequent energy intake. These findings
      suggest that interrupting sedentary behavior may be a promising prevention
      strategy for reducing cardiometabolic risk in children.

PMID- 26312584
TI  - Preventing the transmission of mitochondrial DNA disorders using prenatal or
      preimplantation genetic diagnosis.
AB  - Mitochondrial disorders are among the most common inborn errors of metabolism; at
      least 15% are caused by mitochondrial DNA (mtDNA) mutations, which occur de novo
      or are maternally inherited. For familial heteroplasmic mtDNA mutations, the
      mitochondrial bottleneck defines the mtDNA mutation load in offspring, with an
      often high or unpredictable recurrence risk. Oocyte donation is a safe option to
      prevent the transmission of mtDNA disease, but the offspring resulting from
      oocyte donation are genetically related only to the father. Prenatal diagnosis
      (PND) is technically possible but usually not applicable because of limitations
      in predicting the phenotype. For de novo mtDNA point mutations, recurrence risks
      are low and PND can be offered to provide reassurance regarding fetal health. PND
      is also the best option for female carriers with low-level mutations
      demonstrating skewing to 0% or 100%. A fairly new option for preventing the
      transmission of mtDNA diseases is preimplantation genetic diagnosis (PGD), in
      which embryos with a mutant load below a mutation-specific or general expression
      threshold of 18% can be transferred. PGD is currently the best reproductive
      option for familial heteroplasmic mtDNA point mutations. Nuclear genome transfer
      and genome editing techniques are currently being investigated and might offer
      additional reproductive options for specific mtDNA disease cases. 

PMID- 26312585
TI  - Of "Obamacare" and "CalifornImmunization".

PMID- 26312586
TI  - A 7-Day-Old Infant with Jaundice and Thrombocytopenia.

PMID- 26312587
TI  - Clinical Evaluation of Chronic Cough in Children.
AB  - Cough is a common complaint in pediatrics, and accounts for many visits to the
      pediatrician for evaluation. Cough can be disruptive at school and interrupt
      sleep. In the evaluation of cough, it is important to differentiate between acute
      and chronic cough. Proper evaluation of specific or nonspecific cough through
      history, physical examination, and appropriate laboratory studies should be
      performed. Close observation of all patients to ensure therapeutic benefit is
      important, along with patient education.

PMID- 26312588
TI  - A 4-Week-Old Infant with Scalp Swelling in the Parietal Region.

PMID- 26312589
TI  - A Bony Mass in 2-Year-Old Boy.

PMID- 26312590
TI  - Dermatology: A Morphologic Approach to Differential Diagnosis.

PMID- 26312591
TI  - Pro-Con Debate: Protracted Bacterial Bronchitis as a Cause of Chronic Cough in
      Children.
AB  - Pro: Children with chronic cough present a diagnostic challenge. Protracted
      bacterial bronchitis (PBB) is a chronic, persistent bacterial infection of
      conducting airways defined by the presence of cough for longer than 4 weeks that
      resolves with antimicrobial therapy and without an alternative diagnosis. The
      diagnosis is made by the findings of increased bronchial secretions and edema of
      the lower airways on flexible bronchoscopy and positive cultures on
      bronchoalveolar lavage. It is speculated that an initial respiratory insult such
      as viral infection disrupts normal surface morphology and ciliary function, which
      leads to chronic self-perpetuating inflammation with the formation of bacterial
      biofilms, leading to PBB. PBB is often misdiagnosed as asthma, leading to
      inappropriate and excessive use of steroids. The importance of timely diagnosis
      should be emphasized due to the potential that PBB may be a precursor to chronic
      suppurative lung disease or bronchiectasis if left untreated; however, every
      patient should be adequately assessed to exclude other causes of chronic cough.
      Con: Clinical criteria for the diagnosis of PBB are nonspecific and may not
      distinguish it from other known causes of chronic cough, including viral
      infections. Benefits from antibiotic therapy (particularly prolonged therapy)
      have not been demonstrated. Respiratory conditions are the most common reason for
      antibiotic prescriptions during ambulatory visits in the United States, and many
      of these prescriptions are inappropriate and/or unnecessary. The proposed
      diagnostic criteria and recommendations for the treatment of PBB will lead to
      unnecessary overuse of antibiotics.

PMID- 26312592
TI  - Morphology-Based Diagnosis of Acneiform Eruptions.
AB  - Acne is the most common skin disease. Distinguishing between true acne vulgaris
      and the various acneiform eruptions is important yet sometimes challenging. Given
      the common nature of acne and acneiform eruptions, the pediatrician must be aware
      of these lesion patterns and possess the skills to effectively evaluate the
      pediatric presentation of these eruptions. This article discusses several of the
      most common acneiform eruptions, including neonatal acne and cephalic pustulosis,
      periorificial dermatitis (perioral dermatitis), facial angiofibromas, iatrogenic
      acneiform drug eruptions, and childhood rosacea.

PMID- 26312593
TI  - Differential Diagnosis of Linear Eruptions in Children.
AB  - A 3-year-old girl presented with a linear eruption on her leg for 2 months. She
      was otherwise healthy and well-appearing. Physical examination showed many small,
      erythematous, flat-topped papules coalescing into a linear erythematous plaque.
      At a follow-up visit 9 months later, the eruption had resolved, leaving
      postinflammatory hypopigmentation.When approaching a cutaneous eruption,
      appreciating the pattern of the lesions can be instrumental to arriving at the
      correct diagnosis. For this patient with the acute onset of a plaque on the leg,
      the differential diagnosis is narrowed by the linear distribution of the skin
      lesions. The differential diagnosis of linear eruptions in children includes
      lichen striatus, linear lichen planus, linear psoriasis, inflammatory linear
      verrucous epidermal nevus, incontinentia pigmenti, phytophotodermatitis, and
      allergic contact dermatitis. Of note, many of these conditions manifest in a
      linear manner as a result of cutaneous mosaicism, whereas others are caused by
      external agents contacting the skin.

PMID- 26312594
TI  - A Review of Annular Eruptions in Children.
AB  - Annular, or ring-like, skin lesions are a distinctive cutaneous morphology.
      Dermatologic diagnosis is based on morphology and distribution, and therefore the
      generation of a differential diagnosis based on these criteria can lead to proper
      identification of an eruption. For many dermatologic conditions, considering a
      differential that includes infection, immune phenomenon, neoplastic process,
      physical etiology, and idiopathic process will assure that one thinks broadly and
      is likely to reveal the best diagnosis. Several of these categories are covered
      in this review of annular eruptions in children.

PMID- 26312595
TI  - Blistering Disorders in Children.
AB  - Bullous disorders in children are challenging as they encompass a wide range of
      entities. The etiologies range from inherited to acquired disorders. Some of the
      more common acquired forms include allergic reactions, infections, autoimmune
      mediated conditions, and toxin-mediated conditions. Some eruptions are self
      limited, whereas others can be life-threatening. Obtaining a careful history,
      performing a detailed morphologic examination, recognizing when a skin scraping,
      biopsy, or culture is indicated, and having an understanding of the associated
      pathophysiology allows one to narrow the differential and ultimately arrive at
      the correct diagnosis. This review discusses the more commonly acquired bullous
      eruptions and how to differentiate them.

PMID- 26312596
TI  - Balancing student- and tutor-guidance in problem-based curricula - Response to
      "Is the PBL generation of medical students reliant on Dr Google?".

PMID- 26312597
TI  - Teriparatide Therapy and Reduced Postoperative Hospitalization for Postsurgical
      Hypoparathyroidism.
AB  - IMPORTANCE: Up to 20% of patients undergoing thyroidectomy develop hypocalcemia
      after surgery. Although usually transient, severe symptomatic hypocalcemia may
      occur. Teriparatide acetate (recombinant human parathyroid hormone 1-34) therapy
      can rapidly raise calcium levels. OBJECTIVE: To test the hypothesis that
      teriparatide therapy in patients with postthyroidectomy hypoparathyroidism would
      expedite relief of symptomatic hypocalcemia and reduce the duration of
      hospitalization compared with standard treatment. DESIGN, SETTING, AND
      PARTICIPANTS: Case series of all hospitalized patients 18 years or older treated
      with teriparatide for symptomatic postthyroidectomy hypocalcemia occurring
      immediately after thyroidectomy at Mayo Clinic, Rochester, Minnesota, between
      January 1, 2008, and June 30, 2014. A secondary analysis was performed with
      matched control and cohort groups having postthyroidectomy hypocalcemia of
      similar degree who received standard treatment only. Participants included 8
      hospitalized patients who received teriparatide therapy after 24 hours of
      standard treatment (cases) and eight control patients selected from a cohort of
      1193 thyroidectomies were matched for age, sex, body mass index, and nadir
      calcium levels. INTERVENTION: Teriparatide acetate therapy (20 ug twice daily)
      subcutaneously for 1 week, with the option of continuing at 20 ug/d for up to 3
      weeks. MAIN OUTCOMES AND MEASURES: Safety, symptom resolution, calcium
      supplementation, and duration of hospitalization. RESULTS: Among the 16 case and
      control patients the median nadir calcium level was 7.1 mg/dL in both groups.
      Most patients underwent thyroidectomy for thyroid cancer. Teriparatide therapy
      was safe, with no adverse events noted, and completely eliminated symptomatic
      hypocalcemia in all treated patients within 24 hours of initiation. Hospital
      discharge occurred at a median of 1.0 day (interquartile range, 1.0-1.0 day)
      after teriparatide therapy initiation among cases vs 2.5 days (interquartile
      range, 1.8-3.0 days) after the equivalent clinical point was reached in controls
      (P = .01). This value was 2.0 days in the source cohort (P = .02). On hospital
      discharge, patients had similar calcium levels. Six months after surgery, all
      patients treated with teriparatide showed partial or complete parathyroid
      recovery. Calcium supplementation and calcium levels were comparable between the
      groups. CONCLUSIONS AND RELEVANCE: In this pilot study, teriparatide therapy in
      patients with postthyroidectomy hypoparathyroidism was safe, rapidly eliminated
      hypocalcemic symptoms, and likely reduced the duration of hospitalization. Given
      the limitations of this small study, a large-scale randomized trial is needed to
      verify these results and to assess the long-term effect of teriparatide therapy
      on clinical outcomes.

PMID- 26312599
TI  - Pericytes are involved in the pathogenesis of cerebral autosomal dominant
      arteriopathy with subcortical infarcts and leukoencephalopathy.
AB  - OBJECTIVE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL), the most common inherited small-vessel disease, is
      associated with vascular aggregation of mutant Notch3 protein, dysfunction of
      cerebral vessels, and dementia. Pericytes, perivascular cells involved in
      microvascular function, express Notch3. Therefore, we hypothesize that these
      cells may play a role in the pathogenesis of CADASIL. METHODS: Two-, 7-, and 12
      month-old CADASIL mutant mice (TgNotch3(R169C) ) and wild-type controls were
      examined regarding Notch3 aggregation in pericytes, the coverage of cerebral
      vessels by pericytes, pericyte numbers, capillary density, blood-brain barrier
      (BBB) integrity, astrocytic end-feet, and the expression of astrocytic gap
      junction and endothelial adherens junction protein using immunostaining and
      Western blot analysis. In addition, we examined cerebrovascular CO2 reactivity
      using laser Doppler fluxmetry and in vivo microscopy. RESULTS: With increasing
      age, mutated Notch3 aggregated around pericytes and smooth muscle cells. Notch3
      aggregation caused significant reduction of pericyte number and coverage of
      capillaries by pericyte processes (p < 0.01). These changes were associated with
      detachment of astrocytic end-feet from cerebral microvessels, leakage of plasma
      proteins, reduction in expression of endothelial adherens junction protein, and
      reduced microvascular reactivity to CO2 . Smooth muscle cells were not affected
      by Notch3 accumulation. INTERPRETATION: Our results show that pericytes are the
      first cells affected by Notch3 aggregation in CADASIL mice. Pericyte pathology
      causes opening of the BBB and microvascular dysfunction. Therefore, protecting
      pericytes may represent a novel therapeutic strategy for vascular dementia.

PMID- 26312598
TI  - Association between vitamin D status and age-related macular degeneration by
      genetic risk.
AB  - IMPORTANCE: Deficient 25-hydroxyvitamin D (25[OH]D) concentrations have been
      associated with increased odds of age-related macular degeneration (AMD).
      OBJECTIVE: To examine whether this association is modified by genetic risk for
      AMD and whether there is an association between AMD and single-nucleotide
      polymorphisms of genes involved in vitamin D transport, metabolism, and genomic
      function. DESIGN, SETTING, AND PARTICIPANTS: Postmenopausal women (N = 913) who
      were participants of the Carotenoids in Age-Related Eye Disease Study (CAREDS)
      (aged 54 to <75 years) with available serum 25(OH)D concentrations (assessed
      October 1, 1993, to December 31, 1998), genetic data, and measures of AMD (n =
      142) assessed at CAREDS baseline from May 14, 2001, through January 31, 2004,
      were studied. MAIN OUTCOMES AND MEASURES: Prevalent early or late AMD was
      determined from graded, stereoscopic fundus photographs. Logistic regression was
      used to estimate odds ratios (ORs) and 95% CIs for AMD by the joint effects of
      25(OH)D (<12, >=12 to <20, >=20 to <30, and >=30 ng/mL) and risk genotype
      (noncarrier, 1 risk allele, or 2 risk alleles). The referent group was
      noncarriers with adequate vitamin D status (>=30 ng/mL). Joint effect ORs were
      adjusted for age, smoking, iris pigmentation, self-reported cardiovascular
      disease, self-reported diabetes status, and hormone use. Additive and
      multiplicative interactions were assessed using the synergy index (SI) and an
      interaction term, respectively. To examine the association between AMD and
      variants in vitamin D-related genes, age-adjusted ORs and 95% CIs were estimated
      using logistic regression. RESULTS: Among the 913 women, 550 had adequate levels
      of vitamin D (>=20 ng/mL), 275 had inadequate levels (>=12 to <20 mg/mL), and 88
      had deficient levels (<12 ng/mL). A 6.7-fold increased odds of AMD (95% CI, 1.6
      28.2) was observed among women with deficient vitamin D status (25[OH]D <12
      ng/mL) and 2 risk alleles for CFH Y402H (SI for additive interaction, 1.4; 95%
      CI, 1.1-1.7; P for multiplicative interaction = .25). Significant additive (SI,
      1.4; 95% CI, 1.1-1.7) and multiplicative interactions (P = .02) were observed for
      deficient women with 2 high-risk CFI (rs10033900) alleles (OR, 6.3; 95% CI, 1.6
      24.2). The odds of AMD did not differ by genotype of candidate vitamin D genes.
      CONCLUSIONS AND RELEVANCE: In this study, the odds of AMD were highest in those
      with deficient vitamin D status and 2 risk alleles for the CFH and CFI genotypes,
      suggesting a synergistic effect between vitamin D status and complement cascade
      protein function. Limited sample size led to wide CIs. Findings may be due to
      chance or explained by residual confounding.

PMID- 26312600
TI  - THE SURVEY OF WELL-BEING OF YOUNG CHILDREN: RESULTS OF A FEASIBILITY STUDY WITH
      AMERICAN INDIAN AND ALASKA NATIVE COMMUNITIES.
AB  - This study examined the feasibility of the Survey of Well-Being of Young Children
      (SWYC), a new screener for socioemotional and developmental problems and family
      risk in children birth to age 5 years, for use in American Indian and Alaska
      Native (AIAN) communities. A Community of Learning within the Tribal Early
      Childhood Research Center, composed of university researchers, tribal early
      childhood program staff and evaluators, and federal partners, utilized a
      community-based participatory research approach to guide this qualitative study.
      Thirty-two focus groups and 20 key informant interviews (N = 199) were conducted
      with staff from Head Start, Home Visiting, and Child Care programs;
      pediatricians; behavioral health providers; parents of young children; tribal
      leaders; and other stakeholders in seven diverse AIAN communities. Three themes
      emerged: (a) a strong need to screen early for socioemotional and developmental
      problems and family risk; (b) the importance of a carefully designed process for
      screening; and (c) the importance of examining the content of the SWYC for
      cultural fit specific to tribal communities. Findings support two
      recommendations: (a) the development of guidelines for using the SWYC in tribal
      early childhood settings and (b) a full-scale validation study to determine
      appropriate use with and norms for children in tribal communities. 

PMID- 26312601
TI  - Multicentre study of robotic intersphincteric resection for low rectal cancer.
AB  - BACKGROUND: There is a lack of information regarding the oncological safety of
      robotic intersphincteric resection (ISR) with coloanal anastomosis. The objective
      of this study was to compare the long-term feasibility of robotic compared with
      laparoscopic ISR. METHODS: Between January 2008 and May 2011, consecutive
      patients who underwent robotic or laparoscopic ISR with coloanal anastomosis from
      seven institutions were included. Propensity score analyses were performed to
      compare outcomes for groups in a 1 : 1 case-matched cohort. The primary endpoint
      was 3-year disease-free survival. RESULTS: A total of 334 patients underwent ISR
      with coloanal anastomosis, of whom 212 matched patients (106 in each group)
      formed the cohort for analysis. The overall rate of conversion to open surgery
      was 0.9 per cent in the robotic ISR group and 1.9 per cent in the laparoscopic
      ISR group. Nine patients (8.5 per cent) in the laparoscopic group and three (2.8
      per cent) in the robotic ISR group still had a stoma at last follow-up (P =
      0.075). Total mean hospital costs were significantly higher for robotic ISR (?
      12,757 versus ? 9223 for laparoscopic ISR; P = 0.037). Overall 3-year local
      recurrence rates were similar in the two groups (6.7 per cent for robotic and 5.7
      per cent for laparoscopic resection; P = 0.935). The combined 3-year disease-free
      survival rates were 89.6 (95 per cent c.i. 84.1 to 95.9) and 90.5 (85.4 to 96.6)
      per cent respectively (P = 0.298). CONCLUSION: Robotic ISR with coloanal
      anastomosis for rectal cancer has reasonable oncological outcomes, but is
      currently too expensive with no short-term advantages.

PMID- 26312602
TI  - Solution-Processed Cu2O and CuO as Hole Transport Materials for Efficient
      Perovskite Solar Cells.
AB  - Solution-processed Cu2 O and CuO are used as hole transport materials in
      perovskite solar cells. The cells show significantly enhanced open circuit
      voltage Voc, short-circuit current Jsc, and power conversion efficiency (PCE)
      compared with PEDOT cells. A PCE of 13.35% and good stability are achieved for
      Cu2O cells, making Cu2O a promising material for further application in
      perovskite solar cells.

PMID- 26312603
TI  - The Future of Graduate Medical Education: A Systems-Based Approach to Ensure
      Patient Safety.
AB  - In the past 15 years, there has been growing recognition that improving patient
      safety must be more systems based and sophisticated than the traditional approach
      of simply telling health care providers to "be more careful." Drawing from his
      own experience, the author discusses barriers to systems-based patient safety
      initiatives and emphasizes the importance of overcoming those barriers.
      Physicians may be slow to adopt standardized patient safety initiatives because
      of a resistance to standardization, but faculty in training institutions have a
      responsibility to model safe, effective, systems-based approaches to patient care
      in order to instill these values in the residents they teach. Importantly,
      graduate medical education (GME) is well positioned to influence not only how
      future physicians provide care to patients but also how today's physicians and
      health care systems improve patient safety and care. The necessary systems-based
      knowledge and skills are rooted in both understanding and proficiently
      identifying threats to patient safety, their underlying causes, the development
      and implementation of effective countermeasures, and the measurement of whether
      the threat has been successfully addressed. This knowledge and its application is
      notably absent in the operation of most institutions that sponsor GME training
      programs in terms of didactic instruction and everyday demonstrated proficiency.
      Most important of all, faculty must model the behavior and competencies that are
      desirable in future physicians and not fall into the trap of the "do as I say,
      not as I do" mentality, which can have a corrosive deleterious effect on the next
      generation of physicians.

PMID- 26312604
TI  - Providing Educational Content and Context for Training the Next Generation of
      Physicians in Quality Improvement.
AB  - Amid calls for graduate medical education (GME) to better prepare a workforce
      that can address growing challenges in health care quality and cost, institutions
      must find ways to more effectively educate and engage housestaff in quality
      improvement (QI) initiatives. Although the benefits for trainees and institutions
      alike can be significant, creating and maintaining successful strategies has
      proven challenging. Multiple barriers (e.g., variable backgrounds and needs of
      trainees) have clouded the educational and clinical effectiveness of many
      efforts. Recent findings suggest that trainee engagement in QI is lacking and
      that contextual support for practice-based learning and systems-based practice is
      often suboptimal.Meaningful GME reform must include changes in how institutions
      approach QI education, particularly in how they create appropriate learning
      environments for trainees. Institutions can achieve these goals and foster a
      positive QI culture by aligning housestaff QI teaching with institutional
      priorities in several ways. First, they can create common, institutional-level QI
      curricula to standardize expectations for learners across training levels and
      specialties. Second, they can engage housestaff in ongoing institutional QI
      efforts by encouraging these trainees to develop and execute QI projects or
      assemble QI-focused groups that include faculty and institutional leaders. Third,
      institutions can appoint housestaff to institutional QI committees and have
      housestaff groups review and endorse proposed QI initiatives to enhance
      operational decision making. Institutions can leverage the new Accreditation
      Council for Graduate Medical Education Clinical Learning Environment Review
      program to implement these strategies, measure progress, and realize important
      gains in housestaff QI education.

PMID- 26312605
TI  - A Statewide Strategy for Expanding Graduate Medical Education by Establishing New
      Teaching Hospitals and Residency Programs.
AB  - The graduate medical education (GME) system in the United States is in need of
      reform to ensure that the physician workforce being trained is able to meet the
      current and future health care needs of the population. However, GME funding to
      existing teaching hospitals and programs relies heavily on support from Medicare,
      which was capped in 1997. Thus, new, innovative models to expand GME are needed.
      To address physician shortages, especially in primary care and general surgery
      and in rural areas, the state of Georgia implemented a statewide initiative. They
      increased medical school enrollment by 600 students from 2000 to 2010 and
      committed to establishing new GME programs at new teaching hospitals to train 400
      additional residents by 2018. As increasing the capacity of GME programs likely
      increases the number of physicians practicing in the state, these efforts aim to
      encourage trainees to practice in Georgia. Although new teaching hospitals, like
      these, are eligible for new Medicare funding, this approach to expanding GME also
      incorporates state funding to cover the start-up costs associated with
      establishing a new teaching hospital and GME program.In this article, the authors
      provide background on the current state of GME funding in the United States and
      on the physician workforce and medical education system in Georgia. They then
      outline the steps taken to expand GME by establishing new teaching hospitals and
      programs. They conclude by sharing outcomes to date as well as challenges faced
      and lessons learned so that others can follow this novel model.

PMID- 26312606
TI  - Developing a Pipeline for the Community-Based Primary Care Workforce and Its
      Leadership: The Kraft Center for Community Health Leadership's Fellowship and
      Practitioner Programs.
AB  - PROBLEM: Community health centers (CHCs) face challenges recruiting and retaining
      primary care clinicians. Providing advanced training that enhances clinical
      skills within a public health framework, teaches leadership, protects time for
      scholarly activities, and focuses on the social mission may be a successful
      career development strategy. APPROACH: In July 2012, the Kraft Center for
      Community Health Leadership developed and implemented two 2-year programs to
      develop physician and nursing leaders with blended academic-community career
      paths and identities. The fellowship program for physicians and the practitioner
      program for early-career physicians and advanced practice nurses include mentored
      practice in a CHC; monthly learning days; completion of a community-based
      research project; and, for fellows, matriculation in an MPH program and
      engagement in a bimonthly leadership seminar. OUTCOMES: The first classes of 5
      fellows and 14 practitioners graduated in June 2014. All 5 fellowship graduates
      were offered full-time positions at the CHCs where they practiced, and 2 have
      accepted leadership positions at their CHCs. All 14 practitioner graduates remain
      in community health, 5 have accepted leadership positions, and 2 have obtained
      grants to support ongoing projects. NEXT STEPS: The authors are tracking
      graduates' career paths and the programs' impact on CHCs while modifying the
      programs on the basis of feedback; identifying elements of the programs that may
      be amenable to more cost-effective delivery; and exploring the potential for
      federal funding to support expansion of the practitioner program, and for the
      practitioner program to increase the return on investment provided by the
      National Health Service Corps.

PMID- 26312607
TI  - Desalting by crystallization: detection of attomole biomolecules in picoliter
      buffers by mass spectrometry.
AB  - Sensitive detection of biomolecules in small-volume samples by mass spectrometry
      is, in many cases, challenging because of the use of buffers to maintain the
      biological activities of proteins and cells. Here, we report a highly effective
      desalting method for picoliter samples. It was based on the spontaneous
      separation of biomolecules from salts during crystallization of the salts. After
      desalting, the biomolecules were deposited in the tip of the quartz pipet because
      of the evaporation of the solvent. Subsequent detection of the separated
      biomolecules was achieved using solvent assisted electric field induced
      desorption/ionization (SAEFIDI) coupled with mass spectrometry. It allowed for
      direct desorption/ionization of the biomolecules in situ from the tip of the
      pipet. The organic component in the assistant solvent inhibited the
      desorption/ionization of salts, thus assured successful detection of
      biomolecules. Proteins and peptides down to 50 amol were successfully detected
      using our method even if there were 3 * 10(5) folds more amount of salts in the
      sample. The concentration and ion species of the salts had little influence on
      the detection results. 

PMID- 26312613
TI  - Impact Evaluation of PRONTO Mexico: A Simulation-Based Program in Obstetric and
      Neonatal Emergencies and Team Training.
AB  - INTRODUCTION: Most maternal deaths in Mexico occur within health facilities,
      often attributable to suboptimal care and lack of access to emergency services.
      Improving obstetric and neonatal emergency care can improve health outcomes. We
      evaluated the impact of PRONTO, a simulation-based low-cost obstetric and
      neonatal emergency and team training program on patient outcomes. METHODS: We
      conducted a pair-matched hospital-based trial in Mexico from 2010 to 2013 with 24
      public hospitals. Obstetric and neonatal care providers participated in PRONTO
      trainings at intervention hospitals. Control hospitals received no intervention.
      Outcome measures included hospital-based neonatal mortality, maternal
      complications, and cesarean delivery. We fitted mixed-effects negative binomial
      regression models to estimate incidence rate ratios and 95% confidence intervals
      using a difference-in-differences approach, cumulatively, and at follow-up
      intervals measured at 4, 8, and 12 months. RESULTS: There was a significant
      estimated impact of PRONTO on the incidence of cesarean sections in intervention
      hospitals relative to controls adjusting for baseline differences during all 12
      months cumulative of follow-up (21% decrease, P = 0.005) and in intervals
      measured at 4 (16% decrease, P = 0.02), 8 (20% decrease, P = 0.004), and 12
      months' (20% decrease, P = 0.003) follow-up. We found no statistically
      significant impact of the intervention on the incidence of maternal
      complications. A significant impact of a 40% reduction in neonatal mortality
      adjusting for baseline differences was apparent at 8 months postintervention but
      not at 4 or 12 months. CONCLUSIONS: PRONTO reduced the incidence of cesarean
      delivery and may improve neonatal mortality, although the effect on the latter
      might not be sustainable. Further study is warranted to confirm whether obstetric
      and neonatal emergency simulation and team training can have lasting results on
      patient outcomes.

PMID- 26312614
TI  - Exercise on Progenitor Cells in Healthy Subjects and Patients with Type 1
      Diabetes.
AB  - PURPOSE: To evaluate the acute effect of aerobic exercise (AE) and resistance
      exercise (RE) on the release of endothelial progenitor cell (EPCs,
      CD34+/KDR+/CD45 dim) and vascular function in type 1 diabetes (T1DM). METHODS:
      Fourteen men with T1DM and 5 nondiabetic controls were randomly assigned to 40
      min AE (60% VO 2peak) and RE sessions (60% 1-RM). The study had a crossover
      design, and interventions were 1 wk apart. Venous occlusion plethysmography
      (blood flow, reactive hyperemia, and vascular resistance) and blood collection
      (EPC levels, flow cytometry) were done immediately before and after exercise
      sessions. RESULTS: Patients were 30.3 +/- 1.6 yr-old, HbA1c 7.7% +/- 0.2%;
      controls were 26.8 +/- 2.3 yr-old. Groups did not differ in EPC levels at
      baseline or in relation to exercise. Over time, exercise did not induce changes
      in patients with T1DM, whereas, in controls, EPCs were decreased after AE (
      10.7%, P = 0.017) and increased after RE (+12.2%, P = 0.004). Compared with
      baseline, blood flow increased and vascular resistance decreased after RE in both
      groups. Reactive hyperemia was increased 10 min after AE and RE sessions in
      patients with T1DM (36.5% and 42.0%, respectively) and in controls (35.4% and
      74.3%), but no group differences were observed between groups in response to
      exercise. CONCLUSIONS: Despite the increased vascular reactivity in both groups
      after both exercise sessions, EPCs were only influenced by exercise in controls.
      The unchanged number of EPCs in T1DM after exercise sessions might indicate a
      blunted endothelium regenerating capacity, revealing an early deterioration of
      the functional arterial characteristics not disclosed by only evaluating vascular
      functional variables.

PMID- 26312615
TI  - Acute Warm-up Effects in Submaximal Athletes: An EMG Study of Skilled Violinists.
AB  - BACKGROUND: Warm-up is commonly recommended for injury prevention and performance
      enhancement across all activities, yet this recommendation is not supported by
      evidence for repetitive submaximal activities such as instrumental music
      performance. PURPOSE: The objective of this study is to quantify the effects of
      cardiovascular, core muscle, and musical warm-ups on muscle activity levels,
      musical performance, and subjective experience in skilled violinists. METHODS:
      Fifty-five undergraduate, postgraduate, or professional violinists performed five
      randomly ordered 45-s musical excerpts of varying physical demands both before
      and after a randomly assigned 15-min, moderate-intensity cardiovascular, core
      muscle, musical (technical violin exercises), or inactive control warm-up
      protocol. Surface EMG data were obtained for 16 muscles of the trunk, shoulders,
      and right arm during each musical performance. Sound recording and perceived
      exertion (RPE) data were also obtained. Sound recordings were randomly ordered
      and rated for performance quality by blinded adjudicators. Questionnaire data
      regarding participant pain sites and fitness levels were used to stratify
      participants according to pain and fitness levels. Data were analyzed using two-
      and three-factor ANCOVA (surface EMG and sound recording) and Wilcoxon matched
      pairs tests (RPE). RESULTS: None of the three warm-up protocols had significant
      effects on muscle activity levels (P >= 0.10). Performance quality did not
      significantly increase (P >= 0.21). RPE significantly decreased (P < 0.05) after
      warm-up for each of the three experimental warm-ups; control condition RPE did
      not significantly decrease (P > 0.23). CONCLUSION: Acute physiological and
      musical benefits from cardiovascular, core muscle, and musical warm-ups in
      skilled violinists are limited to decreases in RPE. This investigation provides
      data from the performing arts in support of sports medical evidence suggesting
      that warm-up only effectively enhances maximal strength and power performance.

PMID- 26312616
TI  - Mental Fatigue Impairs Soccer-Specific Physical and Technical Performance.
AB  - PURPOSE: To investigate the effects of mental fatigue on soccer-specific physical
      and technical performance. METHODS: This investigation consisted of two separate
      studies. Study 1 assessed the soccer-specific physical performance of 12
      moderately trained soccer players using the Yo-Yo Intermittent Recovery Test,
      Level 1 (Yo-Yo IR1). Study 2 assessed the soccer-specific technical performance
      of 14 experienced soccer players using the Loughborough Soccer Passing and
      Shooting Tests (LSPT, LSST). Each test was performed on two occasions and
      preceded, in a randomized, counterbalanced order, by 30 min of the Stroop task
      (mentally fatiguing treatment) or 30 min of reading magazines (control
      treatment). Subjective ratings of mental fatigue were measured before and after
      treatment, and mental effort and motivation were measured after treatment.
      Distance run, heart rate, and ratings of perceived exertion were recorded during
      the Yo-Yo IR1. LSPT performance time was calculated as original time plus penalty
      time. LSST performance was assessed using shot speed, shot accuracy, and shot
      sequence time. RESULTS: Subjective ratings of mental fatigue and effort were
      higher after the Stroop task in both studies (P < 0.001), whereas motivation was
      similar between conditions. This mental fatigue significantly reduced running
      distance in the Yo-Yo IR1 (P < 0.001). No difference in heart rate existed
      between conditions, whereas ratings of perceived exertion were significantly
      higher at iso-time in the mental fatigue condition (P < 0.01). LSPT original time
      and performance time were not different between conditions; however, penalty time
      significantly increased in the mental fatigue condition (P = 0.015). Mental
      fatigue also impaired shot speed (P = 0.024) and accuracy (P < 0.01), whereas
      shot sequence time was similar between conditions. CONCLUSIONS: Mental fatigue
      impairs soccer-specific running, passing, and shooting performance.

PMID- 26312617
TI  - Opacification of the Intraocular Lens After Descemet Stripping Endothelial
      Keratoplasty.
AB  - PURPOSE: To report the incidence of opacification of the intraocular lens (IOL)
      after Descemet stripping endothelial keratoplasty (DSEK) in an academic
      ophthalmology clinic. METHODS: In this retrospective case series, all patients
      who underwent DSEK between 2003 and 2013 were included. In 2008, the first
      patient presented with reduced vision as a result of opacification of the IOL in
      our clinic. The period between DSEK surgery and diagnosis of IOL opacification,
      Snellen corrected distance visual acuity before and after the appearance of IOL
      opacification, IOL specifications, and incidence of IOL exchange were assessed.
      RESULTS: A total of 160 eyes were operated on. Opacification was seen in 8 eyes
      (5%) and was diagnosed between 4 and 24 months after DSEK (mean, 9.6; SD, 6.3;
      range, 4-24 months). The mean Snellen corrected distance visual acuity was 0.6
      (SD, 0.2; range, 0.2-0.8) before opacification and 0.3 (SD, 0.2; range, 0.02-0.6)
      after opacification of the IOL occurred. The IOL material was hydrophilic acrylic
      in all patients. In 4 eyes, IOL exchange was performed. CONCLUSIONS:
      Opacification of the IOL can be a vision-threatening late complication after DSEK
      and was seen in 8 of 160 eyes.

PMID- 26312618
TI  - Screening for Subclinical Keratoconus Using Swept-Source Fourier Domain Anterior
      Segment Optical Coherence Tomography.
AB  - PURPOSE: To discriminate between subclinical fellow eyes of patients with
      keratoconus (scKCE) and normal eyes (NE) using swept-source Fourier-domain
      anterior segment optical coherence tomography (SS-OCT). SETTING: University
      Medical Center Hamburg-Eppendorf, Germany. DESIGN: Retrospective cross-sectional
      study. METHODS: NE (both eyes with a KISA% Index <60; N = 213) and scKCE (KISA%
      Index <60, but an index of >100 in the fellow eye; N = 61) eyes were grouped
      according to the KISA% Index. Topography and tomography data were obtained by SS
      OCT (Casia SS1000) and reviewed retrospectively. Receiver operating
      characteristics were performed for Casia SS1000 integrated automated parameters
      and newly computed indices. Additionally, discriminant functions were calculated
      for the automated single parameters, the computed indices, and the combination of
      both. RESULTS: An accuracy >=0.7 was reached for 28 (8 automated and 20 newly
      computed parameters) of 785 parameters. Fourier analysis posterior higher-order
      irregular astigmatism revealed the highest accuracy with 0.81. By combining
      automated parameters with the newly computed indices in 1 discriminant function,
      an area under the curve of 0.92 with a corresponding accuracy of 0.85 was
      achieved. CONCLUSIONS: SS-OCT is able to discriminate between NE and scKCE with
      high accuracy. Automated single parameters and newly computed indices were
      combined to further improve this accuracy.

PMID- 26312619
TI  - Biomechanics of Corneal Ring Implants.
AB  - PURPOSE: To evaluate the biomechanics of corneal ring implants by providing a
      related mathematical theory and biomechanical model for the treatment of myopia
      and keratoconus. METHODS: The spherical dome model considers the inhomogeneity of
      the tunica of the eye, dimensions of the cornea, lamellar structure of the
      corneal stroma, and asphericity of the cornea. It is used in this study for
      calculating a strengthening factor sf for the characterization of different ring
      shaped corneal implant designs. The strengthening factor is a measure of the
      amount of strengthening of the cornea induced by the implant. RESULTS: For ring
      segments and incomplete rings, sf = 1.0, which indicates that these implants are
      not able to strengthen the cornea. The intracorneal continuous complete ring
      (MyoRing) has a strengthening factor of up to sf = 3.2. The MyoRing is,
      therefore, able to strengthen the cornea significantly. CONCLUSIONS: The result
      of the presented biomechanical analysis of different ring-shaped corneal implant
      designs can explain the different postoperative clinical results of different
      implant types in myopia and keratoconus.

PMID- 26312620
TI  - Recovery of the Corneal Stroma Associated With Rapid Reepithelialization Induced
      by the Fibronectin-Derived Peptide PHSRN in 2 Cases of Corneal Perforation Due to
      a Persistent Epithelial Defect.
AB  - PURPOSE: To report 2 cases of corneal perforation associated with a persistent
      epithelial defect (PED), which were treated with eye drops containing the
      fibronectin-derived peptide PHSRN (Pro-His-Ser-Arg-Asn). METHODS: A 67-year-old
      man and a 58-year-old man presented with corneal perforation associated with a
      PED caused by lagophthalmos. PHSRN eye drops were administered 4 times a day to
      both patients. RESULTS: Both patients experienced healing of the epithelial
      defect and closure of corneal perforation within 3 or 4 days after the onset of
      PHSRN treatment. Anterior segment optical coherence tomography also revealed
      recovery of corneal stromal thickness at the lesion site. CONCLUSIONS: PHSRN eye
      drops were effective for the treatment of corneal perforation due to the PED,
      with rapid reepithelialization being followed by full restoration of stromal
      thickness.

PMID- 26312621
TI  - Visual Outcomes and Graft Thickness in Microthin DSAEK--One-Year Results.
AB  - PURPOSE: To evaluate visual outcomes, endothelial graft thickness, and
      complications in microthin Descemet stripping automated endothelial keratoplasty
      (DSAEK). METHODS: A prospective interventional cohort of 130 eyes of 114
      consecutive patients underwent microthin DSAEK. Endothelial graft preparation
      included pachymetry-controlled stromal dehydration to reduce donor thickness
      between 550 and 530 MUm by a custom airflow device, before a single-pass
      microkeratome dissection with a uniform cutting head of 350 MUm to achieve
      microthin endothelial grafts (<130 MUm). Data on visual acuity, graft thickness,
      endothelial cell loss, and complication rates were analyzed. RESULTS: Pachymetry
      controlled donor preconditioning reduced donor thickness on average by 67 MUm
      (range 0-186, SD 44.7) from 590 MUm (range 485-806, SD 53) to 528 MUm (range 480
      620, SD 23), P < 0.01, and allowed graft preparation without any case of
      intraoperative graft loss or perforation. The resultant mean graft thickness was
      94 MUm (SD 25) intraoperatively, 94 MUm (SD 26) at 1 month, and 90 MUm (SD 19) at
      12 months. Of note, 98.2% of eyes without significant visual comorbidity achieved
      best-corrected Snellen acuity of 6/9 or more at 12 months. There was a 35.8% and
      41% reduction in endothelial cell density at 3 and 12 months, respectively.
      Postoperative graft detachment occurred in 5% of cases (1.7% in uncomplicated
      eyes). There was no graft loss during preparation, and none developed immune
      rejection during the study period. CONCLUSIONS: The microthin DSAEK procedure
      offers a simple and safe technique to prepare thin endothelial grafts with a low
      risk of graft wastage, low risk of postoperative detachment, and visual results
      that are comparable to those of other thin endothelial keratoplasty procedures.

PMID- 26312622
TI  - In vivo Confocal Microscopic Analysis of Limbal Stroma in Patients With Limbal
      Stem Cell Deficiency.
AB  - PURPOSE: Using in vivo confocal microscopy, we established that unique
      hyperreflective structures in the anterior limbal stroma of healthy individuals
      represent the limbal stromal niche. The aim of this study was to characterize the
      limbal stromal microarchitecture in patients with limbal stem cell deficiency
      (LSCD). METHODS: After obtaining informed consent, 10 patients with LSCD and 3
      with macular corneal dystrophy were recruited. In vivo confocal imaging of the
      limbus and cornea of the affected and normal eyes was performed using an HRT III
      laser scanning microscope, beyond the epithelium deep into the stroma. RESULTS:
      In the case of LSCD, the limbal epithelium was replaced by conjunctival
      epithelium. A large number of inflammatory and dendritic cells were identified
      along with blood vessels from the epithelium to deep stromal layers. The unique
      hyperreflective niche structures were replaced by homogenously bright fibrous
      structures in all eyes with total LSCD. In patients with partial LSCD, even the
      clinically defined normal limbus had fibrotic stroma. In a patient with focal
      LSCD, only the affected limbal stroma remained fibrotic, whereas the adjacent
      clinically normal limbus had the unique hyperreflective structures. Although the
      opaque corneal stroma appeared bright because of proteoglycan deposition, it was
      possible to identify the normal limbal epithelial and stromal architecture in
      macular corneal dystrophy. CONCLUSIONS: In the case of LSCD, the limbal stromal
      niche was replaced by bright fibrotic structures indicating persistence of damage
      several months after injury. Further studies are required to characterize the
      sequential events occurring in the anterior limbal stroma after injury using this
      noninvasive method.

PMID- 26312623
TI  - Age-Related Changes in Corneal Curvature and Shape: The Shahroud Eye Cohort
      Study.
AB  - PURPOSE: To determine 5-year changes in corneal curvature and asphericity in a
      population-based cohort study of 40 to 64 year olds in Iran. METHODS: This report
      is based on data from the first and second phases of the Shahroud Eye Cohort
      Study conducted in 2009 and 2014, respectively. In this report, Pentacam data
      from 3749 people were used. Extracted variables included the maximum and minimum
      simulated keratometry readings (Kmax and Kmin), the mean radius of sagittal
      curvature (MRSC) in the central 3- and 2-mm rings between 3 to 11 mm from the
      center, and the anterior and posterior asphericity in both study phases. In the
      analysis, repeated-measures analysis of variance was used with a significance
      level of 0.5. RESULTS: During the 5-year period of this survey, Kmax and Kmin
      increased by 0.38 +/- 1.95 diopters and 0.46 +/- 1.97 diopters, respectively.
      According to the mean radius of sagittal curvature indices, the cornea steepened
      in the center up to the 5- to 7-mm ring and flattened in the periphery. The
      increase in anterior and posterior asphericity was 0.15 +/- 0.14 and 0.09 +/-
      0.14, respectively (all P < 0.001). Women, compared to men, showed more change in
      Kmax, Kmin, and posterior asphericity (all P < 0.001), but not in anterior
      asphericity (P = 0.937). CONCLUSIONS: In 40 to 64 year olds, changes are in line
      with maintaining a prolate ellipsoid shape of the cornea. The corneal surface
      undergoes greater changes in women than in men. The anterior surface changes more
      than the posterior.

PMID- 26312624
TI  - Obtaining Lissamine Green 1% Solution for Clinical Use.
AB  - PURPOSE: With new compounding pharmacy laws, the only economically feasible
      approach to using lissamine is through dye-impregnated strips. This research aims
      to determine the concentration of lissamine that can be obtained using a single
      commercially available lissamine strip. With the optimal vital staining requiring
      1% concentration of lissamine, we sought to obtain this concentration using
      supplies in an ordinary ophthalmology clinic. METHODS: A standard curve was
      generated using compounded lissamine green 1% solution. Serial dilutions were
      made with 3 different diluents and measured using a spectrophotometer at a
      wavelength of 633 MUm. Combinations of the number of strips, amount of solvent,
      and absorption time were performed to obtain a 1% solution. Cost analyses were
      performed to select the most economical method. RESULTS: Single lissamine strips
      wetted with any of the diluents produced 0.17% +/- 0.05% (95% confidence
      interval) lissamine solution, a 5-fold weaker concentration than the optimal for
      vital staining. Combinations of 4 strips in 200 MUL (4 drops) for 1 minute and 2
      strips in 200 MUL for 5 minutes were found to reach concentrations of 1%. Cost
      analysis showed that the 2 strip/4 drops/5 minutes method costs $0.67 and the 4
      strips/4 drops/1 minute method $1.27. CONCLUSIONS: Use of a single lissamine
      strip leads to suboptimal concentrations for vital staining. With only the
      addition of disposable microcentrifuge tubes to the clinical setting,
      ophthalmologists can make 1% solutions of lissamine. This solution is both more
      economical and in compliance with both state and national compounding laws.

PMID- 26312625
TI  - Association of 4p14 TLR locus with antibodies to Helicobacter pylori.
AB  - A genome-wide association study among Europeans related polymorphisms of the Toll
      like receptor (TLR) locus at 4p14 and the Fcgamma receptor 2a locus at 1q23.3 to
      Helicobacter pylori serologic status. We replicated associations of 4p14 but not
      1q23.3 with anti-Helicobacter pylori antibodies in 1402 Finnish males.
      Importantly, our analysis clarified that the phenotype affected by 4p14 is
      quantitative level of these antibodies rather than association with
      seropositivity per se. In addition, we annotated variants at 4p14 as expression
      quantitative trait loci (eQTL) associated with TLR6/10 and FAM114A1. Our findings
      suggest that 4p14 polymorphisms are linked to host immune response to H. pylori
      infection but not to its acquisition. 

PMID- 26312626
TI  - Doctorate education and producing knowledge in nursing.

PMID- 26312627
TI  - A critical examination of developments in nursing doctoral education in the
      United States.
AB  - Graduate nursing education in the United States is undergoing major
      transformations, as a result of factors both within nursing and in the larger
      society. OBJECTIVE: In this paper the authors examine the trends and factors that
      are influencing the changes, especially in doctoral education, for both nurse
      scientist and advanced practice preparation. CONCLUSION: The paper provides a
      background that serves as context, it gives an overview of the PhD and the DNP
      degrees, focusing on the recent changes and identifying the most compelling
      issues and concerns, ending with a series of recommendations.

PMID- 26312628
TI  - Doctorate nursing degree in Spain.
AB  - Analytical and descriptive study of the process of change being experienced in
      the Spanish university system over the last decade (2005-2014). OBJECTIVE: To
      describe the structural changes occurring in Nursing Education in Spain, reaching
      access to doctoral studies from the European Convergence Process and the
      subsequent legislative development. METHODOLOGY: Bibliographical review of royal
      decrees and reference literature on the subject of study and descriptive analysis
      of the situation. RESULTS: Carries various changes suffered in the curricula of
      nursing education in the last decade, the legislation of the European Higher
      Education sets the guidelines for current studies of Masters and Doctorates.
      CONCLUSIONS: The implementation of the Master and Doctorate stages after a basic
      degree, which is now possible with the new legislation. A formal beginning made
      of scientific nursing in order to generate their own lines of research led by
      Doctors of nursing who can integrate in research groups under the same condition
      as other researcher, yet now, from the nursing discipline itself.

PMID- 26312629
TI  - Gaining a Doctorate in Nursing in Chile: a path not without its difficulties.
AB  - OBJECTIVE: to analyze in detail the current situation of doctorate training in
      Nursing in Chile. METHODOLOGY: through a historical and contextual analysis of
      the background to the development of postgraduate education in Nursing,
      especially at doctorate level. RESULTS: aspects that limit development were
      identified in national institutionalism of the sciences as well as in higher
      education and health institutions, especially the limited value placed on nursing
      as an area of knowledge in this country, the lack of clear institutional policies
      for postgraduate studies, as well as the postgraduate's re-inclusion into the
      academic and care area, with access to national research funds difficult. FINAL
      CONSIDERATIONS: access to grants and funds, together with recognition as an area
      of knowledge belonging on academic schedules, especially in health institutions,
      are the main challenges to consolidation. One aspect that would enable a more
      rapid advance is through national and international inter-institutional
      agreements, adding together potential, with access to funds for studies and
      academic and student internships, enabling joint research to go ahead.

PMID- 26312630
TI  - Nursing Doctorates in Brazil: research formation and theses production.
AB  - OBJECTIVE: to analyze the formation of nursing doctorates in Brazil, from theses
      production, disciplines and other strategies focusing on research offered by
      courses. METHOD: a descriptive and analytical study of the performance of 18
      doctoral courses in nursing, running from 1982 to 2010, and defended their theses
      between 2010-2012. RESULTS: 502 theses were defended in this period, most linked
      to the online research process of health and nursing care. There are gaps in the
      knowledge of theoretical and philosophical foundations of care, nursing history
      and ethics. There are also weaknesses in the methodological design of the theses,
      with a predominance of descriptive and/or exploratory studies. This was
      consistent with international standards set with regards to the proposition of
      research of disciplines and complementary strategies in forming the doctorate.
      CONCLUSION: despite the efforts and advances in research formation, it is
      essential to expand to more robust research designs with a greater impact on
      production knowledge that is incorporated into practice.

PMID- 26312631
TI  - Doctoral Theses from Nursing Postgraduate Programs in Brazil and their
      Association with the Millennium Development Goals.
AB  - OBJECTIVES: The Millennium Development Goals are centered around combatting
      poverty and other social evils all over the world. Thus, this study seeks to
      identify the Millennium Development Goals as an object of study in theses from
      Postgraduate Nursing Programs in Brazil scoring 5 (national excellence) and 6 or
      7 (international excellence), and evaluate the association between the score for
      the program and achieving the Millennium Development Goals. METHOD: Exploratory
      descriptive document research. Data were collected from the Notes on
      Indicators/Coordination for Higher Education Personnel Improvement for the 15
      Postgraduate Nursing Courses scoring between 5 and 7 in the three-year-period of
      2010/2012. RESULTS: of the 8 Millennium Development Objectives, 6 were dealt with
      in the theses. There was an association (Fisher's exact test p-value=0.0059)
      between the distribution of the theses and the program scores in relation to the
      Millennium Development Objectives (p-valor=0.0347)CONCLUSION: the doctoral theses
      were slightly related to the Millennium Development Objectives, covering the
      population's economic development, health conditions and quality of life. It is
      recommended that Postgraduate Programs in Nursing pay closer attention to the
      Millennium Development Objectives.

PMID- 26312632
TI  - Academic training of nursing professionals and its relevance to the workplace.
AB  - OBJECTIVE: to identify the training nursing professionals receive and its
      relevance to the workplace, as well as professional demand for continuous
      education. METHODOLOGY: this was a descriptive observational study using a
      questionnaire entitled "Training and Adaptation of the Nursing Professional to
      the Workplace" available at: http://enfermeriadocente.es for nursing
      professionals. RESULTS: 53.8% of nurses do not consider the training received to
      be relevant to the needs of the workplace and 94.2% reported that linking
      academic education to the workplace impacts on the quality of care provided.
      CONCLUSIONS: Nursing professionals think that continuous education needs to be
      adjusted to their jobs and careers. Education should be viewed as a continuum,
      which begins with training.

PMID- 26312633
TI  - Analysis of the changes and difficulties arising from kidney transplantation: a
      qualitative study.
AB  - OBJECTIVE: to identify the main gains and stressors perceived by the patient, one
      year subsequent to kidney transplantation. METHOD: a qualitative study, in which
      the data were obtained and analyzed through the Discourse of the Collective
      Subject and frequency counting, with the participation of 50 patients who had
      received kidney transplantation. RESULTS: the sample presented a mean age of 44+/
      12.8 years old, and a predominance of males (62%). The principal positive changes
      provided by the transplant were: return to activities; freedom/independence; well
      being and health; strengthening of the I; and closening of interpersonal
      relationships. The most-cited stressors were: fear; medication; excess of
      care/control; specific characteristics of the treatment; and failure to return to
      the social roles. CONCLUSION: kidney transplantation caused various positive
      changes in the patient's routine, with the return to activities of daily living
      being the most important gain, in the participants' opinion. In relation to the
      stressors, fear related to loss of the graft, and questions relating to the
      immunosuppressive medication were the main challenges to be faced following
      transplantation.

PMID- 26312634
TI  - Assessment of disinfection of hospital surfaces using different monitoring
      methods.
AB  - OBJECTIVE: to assess the efficiency of cleaning/disinfection of surfaces of an
      Intensive Care Unit. METHOD: descriptive-exploratory study with quantitative
      approach conducted over the course of four weeks. Visual inspection,
      bioluminescence adenosine triphosphate and microbiological indicators were used
      to indicate cleanliness/disinfection. Five surfaces (bed rails, bedside tables,
      infusion pumps, nurses' counter, and medical prescription table) were assessed
      before and after the use of rubbing alcohol at 70% (w/v), totaling 160 samples
      for each method. Non-parametric tests were used considering statistically
      significant differences at p<0.05. RESULTS: after the cleaning/disinfection
      process, 87.5, 79.4 and 87.5% of the surfaces were considered clean using the
      visual inspection, bioluminescence adenosine triphosphate and microbiological
      analyses, respectively. A statistically significant decrease was observed in the
      disapproval rates after the cleaning process considering the three assessment
      methods; the visual inspection was the least reliable. CONCLUSION: the
      cleaning/disinfection method was efficient in reducing microbial load and organic
      matter of surfaces, however, these findings require further study to clarify
      aspects related to the efficiency of friction, its frequency, and whether or not
      there is association with other inputs to achieve improved results of the
      cleaning/disinfection process.

PMID- 26312635
TI  - A Path Analysis of Latino Parental, Teenager and Cultural Variables in Teenagers'
      Sexual Attitudes, Norms, Self-Efficacy, and Sexual Intentions.
AB  - OBJECTIVE: to test a theoretical model based on the Parent-Based Expansion of the
      Theory of Planned Behavior examining relation between selected parental, teenager
      and cultural variables and Latino teenagers' intentions to engage in sexual
      behavior. METHOD: a cross-sectional correlational design based on a secondary
      data analysis of 130 Latino parent and teenager dyads. RESULTS: regression and
      path analysis procedures were used to test seven hypotheses and the results
      demonstrated partial support for the model. Parent familism and knowledge about
      sex were significantly associated with parents' attitudes toward sexual
      communication with their teenagers. Parent Latino acculturation was negatively
      associated with parents' self-efficacy toward sexual communication with their
      teenagers and positevely associated with parents' subjective norms toward sexual
      communication with their teenagers. Teenager knowledge about sex was
      significantly associated with higher levels of teenagers' attitudes and
      subjective norms about sexual communication with parents. Only the predictor of
      teenagers' attitudes toward having sex in the next 3 months was significantly
      associated with teenagers' intentions to have sex in the next 3 months.
      CONCLUSION: the results of this study provide important information to guide
      future research that can inform development of interventions to prevent risky
      teenager sexual behavior among Latinos.

PMID- 26312636
TI  - Presence and extent of the primary health care attributes among children
      hospitalized for pneumonia.
AB  - OBJECTIVE: to analyze the presence and extent of the primary health care
      attributes among children hospitalized for pneumonia. METHOD: observational and
      retrospective study with hospital-based case-control design, developed in three
      hospitals associated to the Brazilian Unified Health System, located in a city of
      the State of Sao Paulo, Brazil. The study included 690 children under five years
      old, with 345 cases and 345 controls. RESULTS: both groups scored high for access
      to health services. In contrast, high scores for attributes such as
      longitudinality and coordination of care were observed for the controls. Despite
      low scores, integrality and family counseling were also high for the controls.
      CONCLUSION: knowledge of the aspects involving the primary health care attributes
      and its provision for child care are very important because they have the
      potential to support professionals and managers of the Brazilian Unified Health
      System in the organization of health services.

PMID- 26312637
TI  - Perception of nursing students about couples' violence: knowledge, beliefs and
      professional role.
AB  - OBJECTIVES: to analyse the knowledge, beliefs and perception of the professional
      role that nursing students have, about exerted violence against women in
      relationships. METHOD: a descriptive qualitative study following the ecological
      model through 16 focus groups realized with 112 students from four nursing
      courses of four Spanish universities. RESULTS: the analytical categories were:
      knowledge, professional role, and beliefs about ones behaviour before the victim
      and the abuser. Students are unfamiliar with the characteristics of abuse,
      guidelines, protocols and screening questions and demand patterns for specific
      intervention. They do not identify their own professional role, be it delegated
      or specialized. Beliefs regarding their behaviour with the victim, not guided by
      professional criteria, perceive violence as a specific situation and disassociate
      the prevention of health care. They perceive the abuser as mentally ill,
      justifying the tolerance or delegation of performances. CONCLUSIONS: students
      define preconceived ideas about couples' violence. Speeches reproduce and
      reinforce stereotypical myths, values indicative of inadequate training for
      nursing studies which raises the need to fortify the competencies in relation to
      intimate couples' violence in the curriculum.

PMID- 26312638
TI  - Programmed home visits by nursing professionals to older adults: prevention or
      treatment?

PMID- 26312639
TI  - The family's experience of the child and/or teenager in palliative care:
      fluctuating between hope and hopelessness in a world changed by losses.
AB  - OBJECTIVES: to understand the family's experience of the child and/or teenager in
      palliative care and building a representative theoretical model of the process
      experienced by the family. METHODOLOGY: for this purpose the Symbolic
      Interactionism and the Theory Based on Data were used. Fifteen families with kids
      and/or teenagers in palliative care were interviewed, and data were collected
      through semi-structured interviews. RESULTS: after the comparative analysis of
      the data, a substantive theory was formed "fluctuating between hope and
      hopelessness in a world changed by losses", composed by: "having a life shattered
      ", "managing the new condition", "recognizing the palliative care" and
      "relearning how to live". Hope, perseverance and spiritual beliefs are
      determining factors for the family to continue fighting for the life of their
      child in a context of uncertainty, anguish and suffering, due to the medical
      condition of the child. Along the way, the family redefines values and integrates
      palliative care in their lives. CONCLUSION: staying with the child at home is
      what was set and kept hope of dreaming about the recovery and support of the
      child's life, but above all, what takes it away even though temporarily is the
      possibility of their child's death when staying within the context of the family.

PMID- 26312640
TI  - Impact of chromosome 12p13 variants on ischemic stroke risk.
AB  - BACKGROUND: In 2009, a genome-wide association study (GWAS) identified two
      variants (rs12425791 and rs11833579) near NINJ2 gene that confer susceptibility
      to stroke in Caucasian populations. Recently, a number of studies have been
      conducted to replicate this finding in Asian populations. However, the results
      are conflicting. Thus, we performed a quantitative analysis to summarize the
      evidence regarding the association between these two polymorphisms and ischemic
      stroke risk. METHODS: Pertinent studies were identified by searching PubMed and
      Embase through September 2014. Studies that reported odds ratio (OR) with 95%
      confidence interval (CI) for the association between these two polymorphisms and
      stroke risk were included. RESULTS: Eight independent publications, with 8626
      cases and 8046 controls for rs12425791 and 9142 cases and 8657 controls for
      rs11833579, were included. Overall, significantly increased ischemic stroke risk
      was associated with rs12425791 A allele when all studies were pooled into the
      meta-analysis (AA/GA vs. GG: OR = 1.08, 95% CI: 1.01-1.14). However, rs11833579
      was not associated with increased stroke risk in any genetic model. CONCLUSIONS:
      These findings indicate that rs12425791 G>A polymorphism may be a low-penetrance
      susceptibility marker of stroke in Asian populations and further studies are
      warranted to verify this association.

PMID- 26312641
TI  - Sonic hedgehog multimerization: a self-organizing event driven by post
      translational modifications?
AB  - Sonic hedgehog (Shh) is a morphogen active during vertebrate development and
      tissue homeostasis in adulthood. Dysregulation of the Shh signalling pathway is
      known to incite carcinogenesis. Due to the highly lipophilic nature of this
      protein imparted by two post-translational modifications, Shh's method of transit
      through the aqueous extracellular milieu has been a long-standing conundrum,
      prompting the proposition of numerous hypotheses to explain the manner of its
      displacement from the surface of the producing cell. Detection of high molecular
      weight complexes of Shh in the intercellular environment has indicated that the
      protein achieves this by accumulating into multimeric structures prior to release
      from producing cells. The mechanism of assembly of the multimers, however, has
      hitherto remained mysterious and contentious. Here, with the aid of high
      resolution optical imaging and post-translational modification mutants of Shh, we
      show that the C-terminal cholesterol and the N-terminal palmitate adducts
      contribute to the assembly of large multimers and regulate their shape. Moreover,
      we show that small Shh multimers are produced in the absence of any lipid
      modifications. Based on an assessment of the distribution of various dimensional
      characteristics of individual Shh clusters, in parallel with deductions about the
      kinetics of release of the protein from the producing cells, we conclude that
      multimerization is driven by self-assembly underpinned by the law of mass action.
      We speculate that the lipid modifications augment the size of the multimolecular
      complexes through prolonging their association with the exoplasmic membrane.

PMID- 26312642
TI  - psi-Bufarenogin, a lead compound of anti-cancer drug.

PMID- 26312644
TI  - Thoracoscopic Management of Patent Ductus Arteriosus and Vascular Rings in
      Infants and Children.
AB  - INTRODUCTION: Both patent ductus arteriosus (PDA) and vascular rings often
      require surgical treatment to prevent complications and alleviate symptoms,
      respectively. Management in infants and children has traditionally required an
      open thoracotomy. However, given the known advantages of the thoracoscopic
      approach, increased technical experience, and improved instrumentation, the
      minimally invasive technique to repair these thoracic vascular anomalies has
      grown in popularity. SUBJECTS AND METHODS: We report our experience with
      thoracoscopic PDA ligation and vascular ring division at a single institution.
      From October 1993 to March 2014, 78 patients underwent thoracoscopic PDA
      ligation, and 13 patients presented with vascular rings. Ages ranged from 2 days
      to 17 years (mean, 18 months), and weights ranged from 2 to 60 kg (mean, 8.5 kg)
      for the thoracoscopic PDA group, whereas ages ranged from 6 weeks to 13 years
      (mean, 19 months), and weights ranged from 3.6 to 38 kg (mean, 10 kg) for the
      thoracoscopic vascular ring division group. In the thoracoscopic PDA group, the
      mean operative time was 36 minutes. Complications consisted of one death not
      related to the procedure, one conversion to open for a torn ductus, one
      recurrence requiring re-operative thoracoscopic repair, and one residual PDA
      requiring cardiac catheterization with occlusion. In the vascular ring group, one
      procedure was unable to be completed thoracoscopically and was converted to open.
      In 2 cases, thoracoscopic exploration revealed no significant compression from
      the vascular ring, and dissection was stopped. CONCLUSIONS: Thoracoscopic closure
      of PDA and division of vascular rings are safe and effective techniques that
      minimize physiologic and cosmetic adverse effects.

PMID- 26312645
TI  - Five potential therapeutic agents as antidepressants: a brief review and future
      directions.
AB  - Despite the availability of numerous antidepressants, many patients with
      depression do not show adequate response. The therapeutic lag between drug
      administration and onset of clinical improvement observed with conventional
      antidepressants has led to a need for antidepressants with a novel mechanism of
      action. Recently, five such agents, including acetyl-L-carnitine, scopolamine,
      omega-3 polyunsaturated fatty acids, ketamine, and selective 5-HT7 serotonin
      receptor antagonists, have gained interest as potential antidepressants with
      enhanced symptom control, improved tolerability, and faster onset of action
      compared to conventional antidepressants. This review provides an update and
      critical examination of these five novel therapeutic agents as potential
      antidepressants. 

PMID- 26312646
TI  - Novel targets and stimulation paradigms for deep brain stimulation.
AB  - Deep brain stimulation (DBS) is an accepted therapy for appropriately selected
      patients with movement disorders and psychiatric disease. The recent advances in
      lead technology and the advent of novel stimulation parameters have spurred a
      number of improvements that will likely be implemented in the clinical setting.
      Although the mechanisms and biology of DBS remain poorly understood, the progress
      in our understanding of network level dysfunction has driven the introduction of
      a variety of new targets and approaches to the treatment of human disease. Here
      we summarize the recent advances in novel stimulation patterns and customized
      field shaping. We also review new targets, novel applications of DBS and the
      immediate and long-term horizon for this therapy. 

PMID- 26312648
TI  - Long-term remission of corticosteroid- and cyclophosphamide-resistant Henoch
      Schonlein purpura with rituximab.

PMID- 26312649
TI  - Agrobacterium-mediated transient MaFT expression in mulberry (Morus alba L.)
      leaves.

PMID- 26312650
TI  - Predictors of flourishing for adolescents with asthma.
AB  - OBJECTIVE: The purpose of this study was to examine well-being or flourishing of
      adolescents with asthma as well as factors influencing flourishing for these
      adolescents. METHODS: A secondary analysis of data collected for the 2011-2012
      National Survey of Children's Health was conducted. Flourishing of adolescents
      with and without asthma was compared. Parent coping and anger, child sex and age
      and child flourishing were examined for adolescents with asthma. RESULTS: Youth
      with asthma had lower flourishing than those without this disease. Positive
      parent coping was related to flourishing, while parent anger negatively
      influenced flourishing of adolescents with asthma. Interaction terms were
      significant, indicating that the aforementioned variables interacted with
      adolescent age and sex. CONCLUSIONS: Study results point to a complex
      relationship between parent- and adolescent-level factors and adolescent well
      being. Further research is needed to examine relations among flourishing and
      health outcomes in youth with asthma.

PMID- 26312647
TI  - Immunity and inflammation in status epilepticus and its sequelae: possibilities
      for therapeutic application.
AB  - Status epilepticus (SE) is a life-threatening neurological emergency often
      refractory to available treatment options. It is a very heterogeneous condition
      in terms of clinical presentation and causes, which besides genetic, vascular and
      other structural causes also include CNS or severe systemic infections, sudden
      withdrawal from benzodiazepines or anticonvulsants and rare autoimmune
      etiologies. Treatment of SE is essentially based on expert opinions and
      antiepileptic drug treatment per se seems to have no major impact on prognosis.
      There is, therefore, urgent need of novel therapies that rely upon a better
      understanding of the basic mechanisms underlying this clinical condition.
      Accumulating evidence in animal models highlights that inflammation ensuing in
      the brain during SE may play a determinant role in ongoing seizures and their
      long-term detrimental consequences, independent of an infection or auto-immune
      cause; this evidence encourages reconsideration of the treatment flow in SE
      patients. 

PMID- 26312651
TI  - On the road again after traumatic brain injury: driver safety and behaviour
      following on-road assessment and rehabilitation.
AB  - PURPOSE: To examine pre- and post-injury self-reported driver behaviour and
      safety in individuals with traumatic brain injury (TBI) who returned to driving
      after occupational therapy driver assessment and on-road rehabilitation. METHOD:
      A self-report questionnaire, administered at an average of 4.5 years after
      completing an on-road driver assessment, documenting pre- and post-injury crash
      rates, near-crashes, frequency of driving, distances driven, driving conditions
      avoided and navigation skills, was completed by 106 participants, who had either
      passed the initial driver assessment (pass group n = 74), or required driver
      rehabilitation, prior to subsequent assessments (rehabilitation group n = 32).
      RESULTS: No significant difference was found between pre- and post-injury crash
      rates. Compared to pre-injury, 36.8% of drivers reported limiting driving time,
      40.6% drove more slowly, 41.5% reported greater difficulty with navigating and
      20.0% reported more near-crashes. The rehabilitation group (with greater injury
      severity) was significantly more likely to drive less frequently, shorter
      distances, avoid: driving with passengers, busy traffic, night and freeway
      driving than the pass group. CONCLUSIONS: Many drivers with moderate/severe TBI
      who completed a driver assessment and rehabilitation program at least 3 months
      post-injury, reported modifying their driving behaviour, and did not report more
      crashes compared to pre-injury. On-road driver training and training in
      navigation may be important interventions in driver rehabilitation programs.
      IMPLICATIONS FOR REHABILITATION: Driver assessment and on-road retraining are
      important aspects of rehabilitation following traumatic brain injury. Many
      drivers with moderate/severe TBI, reported modifying their driving behaviour to
      compensate for ongoing impairment and continued to drive safely in the longer
      term. Navigational difficulties were commonly experienced following TBI,
      suggesting that training in navigation may be an important aspect of driver
      rehabilitation.

PMID- 26312652
TI  - Eye-tracking in amyotrophic lateral sclerosis: A longitudinal study of saccadic
      and cognitive tasks.
AB  - A relative preservation of eye movements is notable in ALS, but saccadic
      functions have not been studied longitudinally. ALS overlaps with FTD, typically
      involving executive dysfunction, and eye-tracking offers additional potential for
      the assessment of extramotor pathology where writing and speaking are both
      impaired. Eye-tracking measures (including anti-saccade, trail-making and visual
      search tasks) were assessed at six-monthly intervals for up to two years in a
      group of ALS (n = 61) and primary lateral sclerosis (n = 7) patients, compared to
      healthy age-matched controls (n = 39) assessed on a single occasion. Task
      performance was explored speculatively in relation to resting-state functional
      MRI (R-FMRI) network connectivity. Results showed that ALS patients were impaired
      on executive and visual search tasks despite normal basic saccadic function, and
      impairments in the PLS patients were unexpectedly often more severe. No
      significant progression was detected longitudinally in either group. No changes
      in R-FMRI network connectivity were identified in relation to patient
      performance. In conclusion, eye-tracking offers an objective means to assess
      extramotor cerebral involvement in ALS. The relative resistance of pure
      oculomotor function is confirmed, and higher-level executive impairments do not
      follow the same rate of decline as physical disability. PLS patients may have
      more cortical dysfunction than has been previously appreciated. 

PMID- 26312654
TI  - Social media use in emergency management.
AB  - OBJECTIVE: To identify and illustrate the range of strategies and tactics
      available for emergency managers using social media. DESIGN: This study uses
      content analysis of more than 80 related journal articles, research reports, and
      government documents as well as more than 120 newspaper articles, identified
      through LexisNexis search queries. RESULTS: Three strategies, information
      dissemination, monitoring real-time data, and engaging the public in a
      conversation and/or crowdsourcing, are available to emergency managers to augment
      communication practices via face-to-face contact and through traditional media
      outlets. Academic research has identified several message types disseminated
      during response operations.(1,2) Message types during other emergency phases have
      received less attention; however, news reporting and government reports provide
      best practices and inform this study. This article provides the foundation for a
      more complete typology of emergency management messages. Relatedly, despite
      limited attention in the academic research, monitoring social media feeds to
      accrue situational awareness and interacting with others to generate a
      conversation and/or to coordinate collective action also take place in various
      forms and are discussed. CONCLUSIONS: Findings integrate the fragmented body of
      knowledge into a more coherent whole and suggest that practitioners might
      maximize outcomes through a three-step process of information dissemination, data
      monitoring, and the direct engagement of diverse sets of actors to spur risk
      reduction efforts. However, these steps require time, personnel, and resources,
      which present obstacles for agencies operating under conditions of personnel and
      resource scarcity.

PMID- 26312655
TI  - A cross-sectional survey of patient needs in hospital evacuation.
AB  - To aid development of contingency plans, a cross-sectional survey of inpatient
      needs in the event of a total hospital evacuation within a few hours was
      undertaken. The hospital is a part of a tertiary care facility with a mixed
      surgical and medical population and a relatively large load of emergency
      medicine. A doctor or nurse on each ward registered patients' physical mobility,
      special needs complicating transportation (intensive care, labor, isolation,
      etc), and the lowest acceptable level of care after evacuation. Of the 760
      included patients, 57.8 percent could walk, 20.0 percent needed wheelchair, and
      22.2 percent needed transport on stretcher. Special needs were registered for
      18.2 percent of patients. Only 49.7 percent of patients needed to be evacuated to
      another hospital to continue care on an acceptable level, while 37.6 percent
      could be discharged to their own home, and 12.6 percent could be evacuated to a
      nursing home. Patients in psychiatric wards and high dependency units had
      distinctly different needs than patients in ordinary somatic wards. The
      differences between patients in surgical and nonsurgical wards were minor.
      Patient discharge seems to be a considerable capacity buffer in a hospital crisis
      situation. 

PMID- 26312656
TI  - Active shooter in educational facility.
AB  - The last decade has seen several of the most heinous acts imaginable committed
      against our educational facilities. In light of the recent shooting in Sandy Hook
      Elementary School in Monroe (Newtown), CT, which took the lives of 20 children
      and six employees, a new heightened sense of awareness for safety and security
      among our educational facilities was created.(1) The law enforcement and public
      safety community is now looking to work together with many of the educational
      representatives across the nation to address this issue, which affects the
      educational environment now and in the future. The US public and private
      elementary and secondary school systems' population is approximately 55.2 million
      students with an additional 19.1 million students attending a 2- and 4-year
      college or university. These same public and private school and degree-granting
      institutions employ approximately 7.6 million staff members who can be an
      enormous threshold of potential targets.(2) A terrorist's act, whether domestic,
      international, or the actions of a Lone Wolf against one of our educational
      facilities, would create a major rippling effect throughout our nation.
      Terrorists will stop at nothing to advance their ideology and they must continue
      to advance their most powerful tool-fear-to further their agenda and mission of
      destroying our liberty and the advanced civilization of the Western hemisphere.
      To provide the safety and security for our children and those who are employed to
      educate them, educational institutions must address this issue as well as nullify
      the possible threat to our national security. This thesis used official
      government reports and data interview methodologies to address various concerns
      from within our nation's educational system. Educational personnel along with
      safety and security experts identified, describe, and pinpointed the recommended
      measures that our educational institutions should include to secure our nation
      from within. These modifications of evaluating and updating their current
      emergency operations plan, if implemented correctly, will bring heightened
      awareness, as well as define roles and responsibilities, to everyone involved. In
      addition, these implementations will assist in coordinating and strengthening a
      multiagency partnership's among the public-safety community that will mitigate
      the risk to our student body, faculty, and staff, and strengthen our national
      security. 

PMID- 26312653
TI  - Metastasis of circulating tumor cells: favorable soil or suitable biomechanics,
      or both?
AB  - Metastasis is the end product of a multistep process where cancer cells
      disseminate and home themselves in distant organs. Tumor cell extravasation is a
      rare, inefficient and transient event in nature and makes its studies very
      difficult. Noteworthy, little is known about how cancer cells arrest, adhere and
      pass through the endothelium of capillaries. Moreover, the key events driving
      metastatic growth in specific organs are not well understood. Thus, although
      metastasis is the leading cause of cancer-related death, how cancer cells acquire
      their abilities to colonize distant organs and why they do so in specific
      locations remain central questions in the understanding of this deadly disease.
      In this review, we would like to confront 2 concepts explaining the efficiency
      and location of metastatic secondary tumors. While the "seed and soil" hypothesis
      states that metastasis occurs at sites where the local microenvironment is
      favorable, the "mechanical" concept argues that metastatic seeding occurs at
      sites of optimal flow patterns. In addition, recent evidence suggests that the
      primary event driving tumor cell arrest before extravasation is mostly controlled
      by blood circulation patterns as well as mechanical cues during the process of
      extravasation. In conclusion, the organ tropism displayed by cancer cells during
      metastatic colonization is a multi-step process, which is regulated by the
      delivery and survival of circulating tumor cells (CTCs) through blood
      circulation, the ability of these CTCs to adhere and cross the physical barrier
      imposed by the endothelium and finally by the suitability of the soil to favor
      growth of secondary tumors. 

PMID- 26312657
TI  - Filling the gap between disaster preparedness and response networks of urban
      emergency management: Following the 2013 Seoul Floods.
AB  - OBJECTIVE: To examine the gap between disaster preparedness and response networks
      following the 2013 Seoul Floods in which the rapid transmission of disaster
      information and resources was impeded by severe changes of interorganizational
      collaboration networks. DESIGN/SETTING/METHODOLOGY/APPROACH: This research uses
      the 2013 Seoul Emergency Management Survey data that were collected before and
      after the floods, and total 94 organizations involving in coping with the floods
      were analyzed in bootstrap independent-sample t-test and social network analysis
      through UCINET 6 and STATA 12. RESULTS: The findings show that despite the
      primary network form that is more hierarchical, horizontal collaboration has been
      relatively invigorated in actual response. Also, interorganizational
      collaboration networks for response operations seem to be more flexible grounded
      on improvisation to coping with unexpected victims and damages. CONCLUSIONS:
      Local organizations under urban emergency management are recommended to tightly
      build a strong commitment for joint response operations through full-size
      exercises at the metropolitan level before a catastrophic event. Also,
      interorganizational emergency management networks need to be restructured by
      reflecting the actual response networks to reduce collaboration risk during a
      disaster. ORIGINALITY/INNOVATIONS: This research presents a critical insight into
      inverse thinking of the view designing urban emergency management networks and
      provides original evidences for filling the gap between previously coordinated
      networks for disaster preparedness and practical response operations after a
      disaster.

PMID- 26312658
TI  - Medical interpreters and bilingual school staff: Potential disaster information
      conduits?
AB  - OBJECTIVES: Dissemination of trusted disaster information to limited English
      proficient (LEP) communities may mitigate the negative effects these higher risk
      communities experience in disasters. For immigrant communities, disaster messages
      may be perceived with skepticism, and fear of public officials may affect
      compliance with disaster messages. This study explores whether medical
      interpreters (MIs) and bilingual school staff (BSS) are already informal
      information sources for LEP communities, and could their connection to both
      public service organizations and LEP communities make them ideal efficient,
      trusted disaster information conduits for LEP communities. DESIGN: The authors
      conducted a mixed methods study, which included MI individual interviews, Latino
      community focus groups, an MI employer survey, and school administrator
      interviews. SETTING: To ensure diversity in the sample, data were collected in
      both Los Angeles and Seattle. RESULTS: MIs, MI employers, and schools are willing
      to communicate disaster information to LEP communities. MIs and BSS are connected
      to and share information with LEP communities. Latino LEP communities are eager
      for more disaster information and sources. CONCLUSIONS: The study adds to the
      evidence that a multipronged approach that includes collaborating with
      professionals linked to immigrant communities, such as MIs and BSS, could be an
      effective method of disaster information dissemination. Working with MIs and BSS
      as part of a wider dissemination strategy would promote a community-based
      interpersonal flow of information that would contribute to LEP community's trust
      in the message.

PMID- 26312659
TI  - A whole community approach to emergency management: Strategies and best practices
      of seven community programs.
AB  - OBJECTIVE: In 2011, the Federal Emergency Management Agency (FEMA) published the
      Whole Community Approach to Emergency Management: Principles, Themes, and
      Pathways for Action, outlining the need for increased individual preparedness and
      more widespread community engagement to enhance the overall resiliency and
      security of communities. However, there is limited evidence of how to build a
      whole community approach to emergency management that provides real-world,
      practical examples and applications. This article reports on the strategies and
      best practices gleaned from seven community programs fostering a whole community
      approach to emergency management. DESIGN: The project team engaged in informal
      conversations with community stakeholders to learn about their programs during
      routine monitoring activities, site visits, and during an in-person, facilitated
      workshop. A total of 88 community members associated with the programs examples
      contributed. Qualitative analysis was conducted. RESULTS: The findings
      highlighted best practices gleaned from the seven programs that other communities
      can leverage to build and maintain their own whole community programs. The
      findings from the programs also support and validate the three principles and six
      strategic themes outlined by FEMA. CONCLUSIONS: The findings, like the whole
      community document, highlight the importance of understanding the community,
      building relationships, empowering action, and fostering social capital to build
      a whole community approach.

PMID- 26312660
TI  - A decision support framework for characterizing and managing dermal exposures to
      chemicals during Emergency Management and Operations.
AB  - Emergency Management and Operations (EMO) personnel are in need of resources and
      tools to assist in understanding the health risks associated with dermal
      exposures during chemical incidents. This article reviews available resources and
      presents a conceptual framework for a decision support system (DSS) that assists
      in characterizing and managing risk during chemical emergencies involving dermal
      exposures. The framework merges principles of three decision-making techniques:
      1) scenario planning, 2) risk analysis, and 3) multicriteria decision analysis
      (MCDA). This DSS facilitates dynamic decision making during each of the distinct
      life cycle phases of an emergency incident (ie, preparedness, response, or
      recovery) and identifies EMO needs. A checklist tool provides key questions
      intended to guide users through the complexities of conducting a dermal risk
      assessment. The questions define the scope of the framework for resource
      identification and application to support decision-making needs. The framework
      consists of three primary modules: 1) resource compilation, 2) prioritization,
      and 3) decision. The modules systematically identify, organize, and rank relevant
      information resources relating to the hazards of dermal exposures to chemicals
      and risk management strategies. Each module is subdivided into critical elements
      designed to further delineate the resources based on relevant incident phase and
      type of information. The DSS framework provides a much needed structure based on
      contemporary decision analysis principles for 1) documenting key questions for
      EMO problem formulation and 2) a method for systematically organizing, screening,
      and prioritizing information resources on dermal hazards, exposures, risk
      characterization, and management. 

PMID- 26312661
TI  - The case of a boy with nevus of Ota, extensive Mongolian spot, nevus flammeus,
      nevus anemicus and cutis marmorata telangiectatica congenita: a unique instance
      of phacomatosis pigmentovascularis.
AB  - Phacomatosis pigmentovascularis is a rare, congenital condition characterized by
      a combination of cutaneous melanocytic lesions and vascular malformation. We
      discuss an entirely unique case of Phacomatosis pigmentovascularis with nevus of
      Ota, extensive Mongolian spot, nevus flammeus, nevus anemicus and cutis marmorata
      telangiectatica congenita, which may represent a heretofore undescribed variant
      of phacomatosis pigmentovascularis. 

PMID- 26312662
TI  - Dermatoscopic findings as a complementary tool in the differential diagnosis of
      the etiological agent of tinea capitis.
AB  - Tinea capitis is a scalp infection caused by fungi. In Brazil, the main causative
      agents are Microsporum canis and the Trichophyton tonsurans. Etiological
      diagnosis is based on suggestive clinical findings and confirmation depends on
      the fungus growth in culture. However, it is not always possible to perform this
      test due to lack of availability. We reveal the dermoscopic findings that enable
      distinction between the main causative agents of Tinea capitis, M. canis and T.
      tonsurans. The association of clinical and dermatoscopic findings in suspected
      Tinea capitis cases may help with the differential diagnosis of the etiological
      agent, making feasible the precocious, specific treatment. 

PMID- 26312663
TI  - A case of acquired tufted angioma in adulthood.
AB  - Tufted angioma is a rare vascular tumor whose name derives from its
      histopathological appearance, characterized by tufts of capillaries within the
      dermis. Its etiology and pathogenesis are uncertain. Tufted angioma typically
      occurs during infancy or early childhood and displays various clinical patterns.
      It may present as a subtle stain-like area that later thickens as a large plaque,
      infiltrated or dusky blue-purple lesion, or as an exophytic, firm, violaceous,
      cutaneous nodule. Medical treatment is not necessary for tufted angioma, given
      its benign nature and slow progression. Only clinical follow-up is therefore
      recommended.

PMID- 26312664
TI  - A case of malignant atrophic papulosis with cranial nerve and peripheral nerve
      impairment.
AB  - Malignant atrophic papulosisis is a rare, multisystem obliterative vasculopathy
      of unknown etiology, occasionally involving the cranial nerve. We describe the
      first case of malignant atrophic papulosisis with cranial nerve and peripheral
      nerve involvement in China. A 47-year-old woman presented to our hospital with
      atrophic porcelain white papules over the trunk and extremities, numbness in the
      right calf, vision decrease and impaired movement of the right eye. She was
      diagnosed with malignant atrophic papulosisis, based on characteristic symptoms
      and histopathologic examination. The patient was treated with dipyridamole and
      aspirin for 9 months, but later died of gastrointestinal hemorrhage. We reviewed
      currently available case reports on cranial nerve involvement in malignant
      atrophic papulosisis and emphasized the importance of skin biopsy in diagnosing
      this disease. 

PMID- 26312665
TI  - Anaphylaxis caused by stings from the Solenopsis invicta, lava-pes ant or red
      imported fire ant.
AB  - Ants are social insects with species of medical interest, such as the fire ants
      (Solenopsis sp.). The sting causes inflammation, vesicles and sterile pustules,
      which may cause allergic phenomena and even anaphylactic shock. We describe a
      patient who suffered a large number of stings and an episode of syncope with fall
      in blood pressure and complete regression of symptoms after resuscitation and
      medication for anaphylaxis. Considering the clinical manifestations and images of
      wheals and blisters on the patient's feet at the time of syncope, this report
      should serve as a warning for the diagnosis and treatment of this condition and
      even for counseling and prevention regarding patients exposed to this risk.

PMID- 26312666
TI  - Angioma serpiginosum: report of an unusual acral case and review of the
      literature.
AB  - We report the case of a 35-year-old woman with deep-red asymptomatic macules on
      the plantar and dorsal skin of the right great toe. Histopathologic findings were
      compatible with Angioma serpiginosum. Immunohistochemical stains for estrogens
      and progesterone receptors were negative. Dermoscopy showed an erythematous
      parallel ridge pattern with double rows of irregular dots and globules. We report
      an unusual case of angioma serpiginosum with acral volar skin involvement. The
      dermoscopic features described may aid in the diagnosis of AS in this specific
      skin area. Acral volar skin involvement must be included in the clinical spectrum
      of Angioma serpiginosum and in the differential diagnosis of acral vascular
      lesions.

PMID- 26312667
TI  - Clinical presentation of pili torti--Case report.
AB  - Pili torti also known as 'twisted hairs' (Latin: pili=hair; torti=twisted) is a
      rare, congenital or acquired clinical presentation, in which the hair shaft is
      flattened at irregular intervals and twisted 180o along its axis. It is
      clinically characterized by fragile, brittle, coarse and lusterless hairs, due to
      uneven light reflection on the twisted hair surface. Pili torti may be associated
      with neurological abnormalities and ectodermal dysplasias. There is no specific
      treatment for this condition, but it may improve spontaneously after puberty. We
      report a case of pili torti in a child who presented fragile, brittle, difficult
      to comb hair. The patient had no comorbidities.

PMID- 26312668
TI  - Atypical presentation of histoplasmosis in an immunocompromised patient.
AB  - We present a case of disseminated cutaneous histoplasmosis in a male patient,
      rural worker, HIV positive for 20 years, with a history of irregular use of
      antiretroviral therapy, T cell counts below 50 cells/mm3 and with good response
      to treatment with Itraconazole. We highlight importance of skin lesions in
      clarifying early diagnosis, since this co-infection often leads patients to
      death. 

PMID- 26312669
TI  - Microcystic adnexal carcinoma simulating scarring alopecia.
AB  - The microcystic adnexal carcinoma is a rare, locally aggressive malignant adnexal
      neoplasm associated with significant morbidity. It is often underdiagnosed due to
      clinical and histopathological resemblance with other cutaneous neoplasms and/or
      a combination of lack of familiarity associated with inadequate samples. We
      report a case with clinical hypothesis of scarring alopecia and histopathological
      diagnosis of microcystic adnexal carcinoma with favorable outcome in a follow-up
      of eleven years, after surgical treatment.

PMID- 26312670
TI  - Collision of malignant neoplasms of the skin: basosquamous cell carcinoma
      associated with melanoma.
AB  - Collision tumors are characterized by the coexistence of two cancers in the same
      anatomical site and its pathogenesis remains controversial. Although uncommon,
      the association of basal cell carcinoma and melanocytic nevus is the most common
      among combinations of skin tumors. Even rarer is the association of two malignant
      tumors. We report a case of tumor collision representing melanoma and
      basosquamous cell carcinoma, a combination not previously described in the
      literature, since there are no reported cases of melanoma with this type of basal
      cell carcinoma. 

PMID- 26312671
TI  - Combined acute interstitial pneumonitis and pancytopenia induced by low-dose
      methotrexate in a hemodialysis patient treated for bullous pemphigoid.
AB  - Methotrexate has been widely used for many years in the treatment of a variety of
      diseases. Acute pneumonitis and bone marrow suppression are very serious side
      effects in methotrexate treatment. A 48-year-old man with end-stage renal disease
      undergoing chronic hemodialysis developed combined acute pneumonitis and
      pancytopenia after a cumulative dose of 20 mg methotrexate for bullous
      pemphigoid. Continuous renal replacement therapy (CRRT) can efficiently decrease
      serum methotrexate concentration. A rapid improvement of clinical symptoms and
      resolution of pulmonary opacification were found after CRRT. Blood cell counts
      returned to normal after component blood transfusion and cytokine supportive
      therapy. Patients with impaired renal function are at high risk of methotrexate
      toxicity, and low-dose methotrexate should be prescribed with great caution.

PMID- 26312672
TI  - Cutaneous metastases from gastric adenocarcinoma 15 years after curative
      gastrectomy.
AB  - We report the case of a 38-year-old man, who developed cutaneous metastases in
      the left inguinal groove 15 years after curative gastrectomy for advanced gastric
      adenocarcinoma. Histopathologic examination revealed poorly differentiated
      adenocarcinoma cells. They were stained positive for villin, CDX-2, CKpan (AE1/
      AE3), CEA, CK8/18, CK19, CK7, EMA, Ki-67 (50%), and negative for S-100, CK20,
      CD34, GCDFP-15 and TTF-1. The patient underwent local excision, after the
      presence of other metastases was excluded. Nevertheless, local recurrence
      developed at the surgical bed one year later and PET/CT revealed metastases to
      lymph nodes, bone and skin. He died 2 years after the appearance of cutaneous
      metastases. We have reviewed the literature and described the immunohistochemical
      characteristics of cutaneous metastases from gastric adenocarcinoma. 

PMID- 26312673
TI  - Dapsone in the treatment of pemphigus vulgaris: adverse effects and its
      importance as a corticosteroid sparing agent.
AB  - Pemphigus vulgaris is an autoimmune disease characterized by suprabasal blisters
      with acantholysis, which has a fatal course in a large number of untreated
      patients. Systemic corticosteroid therapy is considered first-line therapy.
      Adjuvant treatment with the goal of sparing corticosteroids include, among
      others, dapsone. This drug is not without side effects and its use requires
      clinical and laboratory control. We present a patient with PV initially managed
      with suboptimal dose of prednisone, evolving into drug-induced hepatitis after
      introduction of dapsone. 

PMID- 26312674
TI  - HTLV-1-associated infective dermatitis and probable HTLV-1- associated myelopathy
      in an adolescent female.
AB  - Human T cell lymphotropic virus type 1 (HTLV-1)-associated infective dermatitis
      (ID) is a chronic, severe and recurrent eczema occurring during childhood in
      patients vertically infected with HTLV-1. HTLV-1-associated myelopathy/tropical
      spastic paraparesia (HAM/ TSP) is slow and progressive. We report the case of an
      adolescent female from a non-endemic area for HTLV-1 who presents ID and, most
      likely, associated HAM/TSP. 

PMID- 26312675
TI  - Dermatosis neglecta.
AB  - Dermatosis neglecta is the name of a skin condition characterized by papules and
      polygonal plaques, which are sometimes warty, brownish and hyperpigmented,
      adherent and symmetric, though removable with ethyl or isopropyl alcohol. It
      occurs due to inadequate skin cleansing causing accumulation of sebum, sweat,
      keratin and impurities. Its occurrence, though little reported, is frequent. The
      main differential diagnosis is the Terra firma-forme dermatosis. The treatment is
      simple, with exfoliation, moisturizing and even rubbing of alcohol. Causes of
      negligence on the patient's side, which can range from hygiene carelessness to
      psychiatric disorders, local hypersensitivity, limbs negligence or motor
      paralysis, should be investigated. We illustrate the case of dermatosis neglecta
      in a 45-years old patient admitted with pulmonary sepsis.

PMID- 26312676
TI  - Segmental Darier's disease: a presentation of difficult diagnosis.
AB  - Darier's disease is a rare autosomal dominant genodermatosis. It has an estimated
      prevalence of 1 in 55,000 to 100,000 individuals, regardless of gender. It is
      characterized by multiple keratotic papules on the seborrheic areas of the trunk,
      scalp, forehead and flexures, and the clinical picture is worsened by heat, sun
      exposure, perspiration and mechanical trauma. Histopathology observed loss of
      epithelial adhesion and abnormal keratinization. About 10% of cases present in
      the localized form of the disease. We report a case of segmental Darier's Disease
      Type I and discuss the main characteristics of this condition. 

PMID- 26312677
TI  - Severe Darier's disease in a psychiatric patient.
AB  - Darier's disease is characterized by dense keratotic lesions in the seborrheic
      areas of the body such as scalp, forehead, nasolabial folds, trunk and inguinal
      region. It is a rare genodermatosis, an autosomal dominant inherited disease that
      may be associated with neuropsichiatric disorders. It is caused by ATPA2 gene
      mutation, presenting cutaneous and dermatologic expressions. Psychiatric symptoms
      are depression, suicidal attempts, and bipolar affective disorder. We report a
      case of Darier's disease in a 48-year-old female patient presenting severe
      cutaneous and psychiatric manifestations. 

PMID- 26312678
TI  - Eccrine poroma and porocarcinoma on the same unusual location: report on two
      cases.
AB  - Eccrine poroma is a benign adnexal tumour of the uppermost portion of the
      intraepidermal eccrine sweat gland duct and acrosyringium. Eccrine porocarcinoma
      is the malignant phenotype arising from the intraepidermal portion of the eccrine
      sweat gland duct epithelium or from pre-existing eccrine poroma. Both commonly
      occur in the palms or sides of the feet; these areas have a high concentration of
      eccrine sweat glands. We describe two respective cases of benign and malignant
      eccrine poroma on the scrotum, which entailed good excisional results. 

PMID- 26312679
TI  - Leprosy type-I reaction episode mimicking facial cellulitis--the importance of
      early diagnosis.
AB  - Leprosy is an easily recognizable disease due to its dermato-neurological
      manifestations. It must be present in the physician's diagnostic repertoire,
      especially for those working in endemic areas. However, leprosy reaction is not
      always easily recognized by non-dermatologists, becoming one of the major
      problems in the management of patients with leprosy, as it presents clinical
      complications characterized by inflammatory process, accompanied by pain, malaise
      and sometimes the establishment or worsening of the patient's disabilities. We
      report the case of a patient with type-1 periorbital reaction admitted to the
      hospital, diagnosed and treated as facial cellulitis, whose late diagnosis may
      have contributed to the appearance or worsening of facial neuritis.

PMID- 26312680
TI  - Possibly drug-induced palpable migratory arciform erythema.
AB  - Palpable migratory arciform erythema is an entity of unknown etiology, with few
      published cases in the literature. The clinical and histopathological features of
      this disease are difficult to be distinguished from those of Jessner's
      lymphocytic infiltration of the skin, lupus erythematous tumidus and the deep
      erythema annulare centrifugum. We describe here the first two Brazilian cases of
      palpable migratory arciform erythema. The patients presented with infiltrated
      annular plaques and erythematous arcs without scales. These showed centrifugal
      growth before disappearing without scarring or residual lesions after a few days.
      They had a chronic course with repeated episodes for years. In addition, these
      cases provide evidence of a drug-induced etiology. 

PMID- 26312681
TI  - Scleredema associated with Sjogren's syndrome.
AB  - Scleredema adultorum of Buschke is a rare disorder characterized by diffuse
      swelling and non-pitting induration of the skin usually involving the face, neck,
      arms and upper trunk. It has been associated with previous infectious diseases,
      diabetes, paraproteinemia and, more rarely, malignant neoplasms or autoimmune
      disorders. We report the case of a 30-year-old man who presented with a 2-year
      history of scleredema. Further investigation led to the diagnosis of primary
      Sjogren's syndrome. The association between scleredema and autoimmune disorders
      has been rarely seen. To our knowledge, there are no other reports describing the
      association between primary Sjogren's syndrome and scleredema adultorum of
      Buschke. 

PMID- 26312682
TI  - Sporotrichosis in an unusual location--Case report.
AB  - Sporotrichosis is the most common subcutaneous mycosis. It is caused by the
      dimorphic fungus Sporothrix schenckii, and the infection is usually acquired by
      traumatic inoculation. We describe a case of sporotrichosis in an uncommon
      location with an unusual mode of transmission. A 49-year-old female patient who
      lived in an urban area of Rio de Janeiro presented with involvement of the left
      ear. No history of contact with soil, plants or animals was elicited. The
      suspected source of infection was a pair of handmade wooden earrings. The delay
      in the diagnosis and treatment resulted in higher morbidity, unsightly scarring
      and loss of ear lobe. 

PMID- 26312683
TI  - Eosinophilic ulcer of the tongue--Case report.
AB  - Eosinophilic ulcer of the oral mucosa is a rare, self-limiting, chronic and
      benign lesion of unknown pathogenesis that affects the oral mucosa. We present
      the case of a 65 year-old Caucasian female with a five month history of a painful
      ulcer on the lateral side of her tongue. The ulcer was not adhered to the
      underlying structures and there was no evidence of regional lymph node
      involvement. Laboratory examinations and X-rays revealed no abnormalities.
      Topical treatments had been performed without any improvement. Histopathological
      examination showed an ulcerated surface and mixed inflammatory infiltrate with
      several eosinophils extending into the mucosa and submucosa. No cellular atypia
      was observed. Based on the patient-s history and mucosal biopsy, a final
      diagnosis of eosinophilic ulcer of the oral mucosa was made.

PMID- 26312684
TI  - Wolf's isotopic response, presenting as lichen planus.
AB  - The term "Wolf's isotopic response" describes the occurrence of a new skin
      disorder at the site of another unrelated and already healed skin disease. In
      most cases, herpes zoster is the inicial disease. Different disorders may develop
      on the same site, most commonly granulomatous and lichenoid reactions,
      infiltration of hematologic diseases, skin tumors and infections. There are few
      related cases of lichen planus presenting as isotopic response. We report a case
      of a 74 year-old woman, with multiple itchy, rose-colored and shiny papules that
      developed at site of previously healed herpes zoster, on the right arm and
      shoulder. The pathogenesis of this phenomenon is still unknown and further
      studies are needed. 

PMID- 26312685
TI  - Proliferating pilomatricoma--Case report.
AB  - Proliferating pilomatricoma is proliferative, rare tumor variant of
      pilomatricoma. It is a benign neoplasm of hair matrix that can have potentially
      involve local recurrence. We report the case of a 60-year-old man who presented
      an asymptomatic nodule on the scalp. Histological exam demonstrated a basaloid
      epithelium at the periphery, filled with eosinophilic cornified material
      containing shadow cells. The tumor was excised and there was no evidence of
      recurrence one year later. 

PMID- 26312686
TI  - Type 2 segmental glomangioma--Case report.
AB  - Glomus tumors originate from modified perivascular muscle cells. The most common
      form is the solitary one. The multiple form may be associated with dominant
      genetic inheritance. We report a case of a patient with hemangiomatous lesions on
      the calcaneus and wrist since birth. In 6 years, there was progression of lesions
      throughout the body. Multiple glomangiomas are asymptomatic and more common in
      childhood. They can be confused with other vascular malformations.
      Histopathological diagnosis is essential. The case shows a type 2 segmental
      manifestation that can be explained by genetic mutation leading to the loss of
      heterozygosity. As the child grows, the lesions may disseminate due to mutation
      in distant parts of the skin. Literature shows few reports. The treatment is
      conservative. 

PMID- 26312687
TI  - Granulomatosis with polyangiitis, a new nomenclature for Wegener's Granulomatosis
      -Case report.
AB  - The granulomatosis with polyangiitis, initially known as Wegener's
      granulomatosis, is a small and medium vessels vasculitis. It's classic form
      presents a triad: necrotizing granuloma of respiratory tract, necrotizing
      cutaneous vasculitis and glomerulonephritis. This vasculitis has cytoplasmic
      antineutrophil antibodies as signal. This work illustrates a case, of
      multisystemic rare disease, in which the segment and treatment were considered
      satisfactory for symptoms remission. 

PMID- 26312688
TI  - Cutaneous histoplasmosis as a complication after anti-TNF use--Case report.
AB  - Anti-TNF agents are effective in the treatment of psoriasis. However, they render
      individuals more susceptible to infections. We report an atypical case of
      histoplasmosis in an immunosuppressed patient due to anti- TNF therapy. A patient
      who used anti-TNF for the treatment of psoriasis had had a lesion on the right
      eyebrow since discontinuation of the medication. The diagnostic hypothesis was
      basal cell carcinoma, but the histopathological examination was compatible with
      histoplasmosis. 

PMID- 26312689
TI  - Post-kala-azar dermal Leishmaniasis in two different clinical contexts.
AB  - In Brazil, visceral Leishmaniasis is caused by Leishmania chagasi. The
      development of cutaneous lesions in visceral leishmaniasis patients has been
      described in two different clinical contexts. Patients with compromised immunity
      can develop skin lesions as a direct consequence of a current visceral disease.
      Equally, patients with a history of kala-azar and progressive, immune improvement
      occasionally develop skin lesions as a consequence of immune reconstitution
      inflammatory syndrome. These cases manifest in similar fashion to the classic
      form of post-kala-azar dermal Leishmaniasis. We describe different cases that
      exemplify these two clinical presentations.

PMID- 26312690
TI  - Primary cutaneous follicle center lymphoma simulating basal-cell carcinoma on the
      nasal ala.
AB  - Primary cutaneous B-cell lymphomas (PCBCLs) constitute 25% of all primary
      cutaneous lymphomas. They present in the skin with no evidence of systemic or
      extracutaneous disease at the time of diagnosis, after adequate staging. Primary
      cutaneous B-cell lymphomas differ significantly from their nodal counterparts in
      relation to both clinical behavior and prognosis. The distinction between primary
      and secondary B-cell lymphomas is essential for defining prognosis/course of
      action. Such distinction is also very difficult to make, since primary and
      secondary B-cell lymphomas are clinically and histologically indistinguishable.
      We report the case of a patient with primary cutaneous follicle center lymphoma
      who underwent surgical excision. 

PMID- 26312691
TI  - Membranous lipodystrophy: case report and review of the literature.
AB  - Membranous lipodystrophy is a distinct type of membranocystic fat necrosis. It is
      associated with many local and systemic diseases, including vascular disorders.
      The histopathological changes which characterize this phenomenon are variably
      sized cysts in the fat lobules of the subcutaneous tissue, which are surrounded
      by eosinophilic membranes projecting into the cystic space. We report a case of
      secondary membranous lipodystrophy associated with both hypertension and venous
      insufficiency. 

PMID- 26312692
TI  - Bullous and hemorrhagic lichen sclerosus--Case report.
AB  - Lichen sclerosus is a chronic inflammatory disease, usually located in the
      genital area. The etiology of lichen sclerosus is multifactorial, with
      participation of genetic, autoimmune, infectious and hormonal factors. Bullous
      clinical form stems from hydropic degeneration of the basal membrane,
      constituting a less frequent variant of the disease. In this work, we report the
      case of a female patient, 55 years old, who in the last three years presented
      whitish plaques, with horny spikes, located on back and arms. Some of these
      lesions evolved with hemorrhagic blisters, which after histopathological
      examination confirmed the diagnosis of bullous and hemorrhagic lichen sclerosus.
      The patient was treated with high-potency topical corticosteroid for two months,
      resulting in remission of bullous and hemorrhagic lesions. 

PMID- 26312693
TI  - Drug-induced lupus with leukocytoclastic vasculitis: a rare expression associated
      with adalimumab.
AB  - TNF alpha antagonist-induced lupus-like syndrome is a rare condition which
      predominantly affects women (4:1). The average age of onset is 46-51 years. It
      occurs after exposure to TNF alpha antagonist and disappears after
      discontinuation of such agents. The pathogenic mechanism for development of the
      TNF alpha antagonist-induced lupus-like syndrome is not fully defined. It is
      believed that the medication induces apoptosis, leading to an accumulation of
      nucleosomal antigens of apoptotic cells. This would cause autoantibodies to be
      produced by susceptible individuals. The most common cutaneous manifestations
      include maculopapular exanthem, malar rash, alopecia, photosensitivity and, more
      rarely, vasculitis. Extracutaneous manifestations include: fever, weight loss,
      arthritis or arthralgia, myositis and hematological abnormalities. Antinuclear
      antibody may be positive in 80% of cases and anti-histone antibody is considered
      a disease marker for TNF alpha antagonist-induced lupus-like syndrome. Treatment
      corresponds to drug discontinuation. We report a rare case of sub-acute cutaneous
      lupus erythematosus with leukocytoclastic vasculitis induced by adalimumab in a
      42-year-old patient. 

PMID- 26312694
TI  - Anti-TNF-alpha and hydralazine drug-induced lupus.
AB  - Drug-induced lupus is a rare drug reaction featuring the same symptoms as
      idiopathic lupus erythematosus. Recently, with the introduction of new medicines
      in clinical practice, an increase in the number of illness-triggering implicated
      drugs has been reported, with special emphasis on anti-TNF-alpha drugs. In the up
      to-date list, almost one hundred medications have been associated with the
      occurrence of drug-induced lupus. The authors present two case reports of the
      illness induced respectively by hydralazine and infliximab, addressing the
      clinical and laboratorial characteristics, diagnosis, and treatment. 

PMID- 26312695
TI  - Frontal cutaneous meningioma--Case report.
AB  - Cutaneous meningiomas are rare tumors most commonly located on the scalp. We
      report the case of a 55-year-old male who presented with a 2 x 3 cm tumoral
      lesion on the forehead. The lesion was hard, adherent and covered by normal skin.
      Incisional biopsy revealed a proliferation of monomorphic round cells, organized
      in nests and focally forming pseudovascular spaces. Immunohistochemical study
      revealed positivity for epithelial antigen membrane and vimentin. Vascular
      markers, cytokeratins and S100 protein were negative. A brain CT scan did not
      show any evidence of intracranial meningioma. The authors describe the case of a
      cutaneous frontal meningioma in probable relation with previous cranioencephalic
      trauma.

PMID- 26312696
TI  - Cutaneous metastasis of a breast cancer diagnosed 13 years before.
AB  - Metastasis is defined as a neoplastic lesion originating from another primary
      tumor, with which it is no longer in contact. Cutaneous metastases result from
      lymphatic embolization, hematogenous or contiguous dissemination or also direct
      implantation during surgical procedures. In women, the tumor most likely to
      metastasize to skin is breast cancer, which may manifest as papulonodular
      neoplastic lesions. We report the case of a 66 years old female patient,
      presenting papulonodular lesions 13 years after the initial treatment with
      surgery and chemotherapy for a cancer of the left breast.

PMID- 26312697
TI  - Disseminated cutaneous atypical mycobacteriosis by M. chelonae after
      sclerotherapy of varicose veins in a immunocompetent patient: a case report.
AB  - Atypical mycobacteria are saprophytic organisms not transmitted from person to
      person, which affect mainly immunosuppressed but also immunocompetent
      individuals. We present a case of atypical mycobacteriosis after a vascular
      procedure, with widespread cutaneous lesions associated with polyarthralgia.
      Mycobacterium chelonae was identified by the polymerase chain reaction (PCR)
      method. The patient showed improvement after treatment with three antibiotics.
      Mycobacterium chelonae causes skin lesions after invasive procedures. The
      clinical form depends on the immune state of the host and on the entry points.
      The diagnosis is based essentially on culture and the mycobacteria is identified
      by PCR. We highlight the importance of investigating atypical mycobacteriosis
      when faced with granulomatous lesions associated with a history of invasive
      procedures. 

PMID- 26312698
TI  - Pre-tibial myxedema: treatment with intralesional corticosteroid.
AB  - The pretibial myxedema is a manifestation of Graves' disease characterized by
      accumulation of glycosaminoglycans in the reticular dermis. The dermopathy is
      self-limiting but in some cases may cause cosmetic and functional damage.
      Conventional treatment is use of topical steroids under occlusive dressing,
      however the intralesional application has shown good results. We present a case
      of pretibial myxedema treated with single injection of intralesional
      corticosteroid. 

PMID- 26312699
TI  - Follicular mucinosis: an important differential diagnosis of leprosy in an
      endemic area.
AB  - Primary follicular mucinosis is a rare dermatosis characterized by the
      accumulation of mucin in the follicular epithelium and sebaceous glands.
      Clinically, it is characterized by the presence of papules or well-circumscribed
      and infiltrated plaques. In this paper, we report the case of a female patient,
      seven years old, evolving for three months with an asymptomatic, erythematous and
      infiltrated plaque located in the chin region. The research of thermal, pain and
      tactile sensitivity was inconclusive. Histological findings confirmed the
      diagnosis of follicular mucinosis. There was regression of the lesion with the
      use of medium potency topical corticosteroids for 20 days. The pathogenesis of
      follicular mucinosis remains unknown, being in some cases associated with
      lymphoproliferative disorders. In endemic areas of leprosy, isolated and
      infiltrated follicular mucinosis lesions should be further differentiated from
      leprosy. 

PMID- 26312700
TI  - Multiple giant angiokeratoma of Fordyce on the shaft of the penis masquerading as
      keratoacanthoma.
AB  - The term 'angiokeratoma' includes a wide range of dermatological conditions of
      hyperkeratotic vascular disorders with a similar histologic combination of
      hyperkeratosis and superficial dermal vascular ectasia. Angiokeratomas can be
      classified into localized and systemic forms. Angiokeratoma of Fordyce (AKF) is a
      localized form of angiokeratoma, clinically characterized by 1- to 6-mm, black,
      blue, or dark red, dome-shaped papules located on the scrotum, shaft of penis,
      labia majora, clitoris, inner thigh, and lower abdomen. We describe herein a case
      of giant angiokeratoma of Fordyce on shaft of the penis in an elderly man,
      clinically masquerading as keratoacanthoma. 

PMID- 26312701
TI  - Multiple minute digitate hyperkeratosis--a peculiar entity.
AB  - Multiple minute digitate hyperkeratosis is a rare, non-follicular dermatosis,
      with fewer than 30 cases described worldwide. It can be either acquired or
      inherited in an autosomal dominant pattern. We describe the case of an 83-year
      old patient with life-long, multiple, digitate, milimetric lesions, and a
      positive family history for the same dermatosis. 

PMID- 26312702
TI  - Cellular neurothekeoma: case report and its (un) relation with nerve sheath
      myxoma.
AB  - Neurothekeoma is an uncommon, benign neoplasm presenting in young adults,
      primarily on the head and neck. It was initially related to nerve sheath myxoma
      but with the advent of immunohistochemistry, new insights into its cellular
      differentiation and origin have emerged, unlinking Neurothekeoma and nerve sheath
      myxoma. Herein we describe a 19-year-old male who had had a frontal, flesh
      colored, asymptomatic papule for 2 years. Histology showed a dermal fusocellular
      spindle cell tumor, including an eosinophilic cytoplasm with mild cellular
      pleomorphism and moderately dense fibrous stroma. IHQ was positive for CD10 and
      negative for S100 and Claudin-1. These findings were compatible with cellular
      Neurothekeoma. The lesion was completely extirpated and at the 6-month follow-up,
      the patient was asymptomatic and had experienced no recurrences.

PMID- 26312703
TI  - Cerebriform sebaceous nevus: a rare presentation.
AB  - A 13-year-old boy presented congenital, raised, yellowish colored plaques with
      fibroelastic consistency, which were velvety in appearance, alopecic, with
      clearly defined limits and sulci or well-marked meandering invaginations, a
      cerebriform appearance on the upper part of the right ear, accompanied by
      alopecia in the temporomandibular region-parietal. The lesion was asymptomatic.
      Histopathologic examination revealed acanthosis, hyperkeratosis, papillomatosis
      and follicular plugging in the epidermis. The upper dermis showed underdeveloped
      hair follicles with sebaceous glands, consistent with sebaceous nevus. There were
      no skeletal, cardiological, ophthalmological or neuropsychomotor changes; nor
      were there any records of relevant pathologies in the family history. The patient
      complained of his appearance, experiencing aesthetic and social issues. Following
      a diagnosis of cerebriform nevus sebaceous, complete excision was performed with
      excellent aesthetic results.

PMID- 26312704
TI  - Azathioprine-induced accelerated cutaneous and pulmonary nodulosis in a patient
      with rheumatoid arthritis.
AB  - We report the case of a 42-year-old female with a 5-year history of rheumatoid
      arthritis treated with Rituximab and Azathioprine. Three months after the
      initiation of Azathioprine, the patient started with dry cough and noted the
      rapid development of multiple subcutaneous nodules on her right leg. CT scan of
      the chest demonstrates pulmonary nodulosis. Skin biopsy was compatible with
      rheumatoid nodule. A diagnosis of "accelerated cutaneous and pulmonary nodulosis"
      was considered. Azathioprine was discontinued and Rituximab was restarted. Two
      months later, most of the subcutaneous nodules had disappeared. This is the
      second case report of accelerated rheumatoid nodulosis in association with
      Azathioprine treatment. 

PMID- 26312705
TI  - New drugs, new challenges for dermatologists: mucocutaneous ulcers secondary to
      everolimus.
AB  - Everolimus, a mammalian target of rapamycin inhibitor, is an emerging drug, which
      is being increasingly applied in oncology and solid organ transplantation. Oral
      ulcers are a frequent side effect associated with this immunosupressor. We report
      the case of a renal transplant recipient who developed disfiguring oral and
      perianal ulcers secondary to everolimus's toxicity. This is probably the first
      report of perianal involvement. Dermatologists need to be aware of the potential
      mucocutaneous adverse effects related to these new drugs that are becoming
      evermore common in our clinical practice. 

PMID- 26312706
TI  - The role of immunohistochemistry in the Muir-Torre Syndrome.
AB  - Muir-Torre Syndrome is defined by the coexistence of sebaceous skin tumors and
      internal malignancies. Mutations in the DNA mismatch repair genes are found in
      the inherited form of the disease, resulting in the absence of crucial enzymes
      involved with DNA replication process. This case describes a patient with
      sebaceous adenoma and colorectal carcinoma, meeting the criteria for Muir-Torre
      Syndrome. The immunohistochemical analysis of the skin lesion was an important
      tool to confirm the diagnosis, as it revealed nuclear negativity for MSH2 and
      MSH6. 

PMID- 26312707
TI  - Use of tumor necrosis factor alpha (TNF alpha) antagonists in a patient with
      psoriasis and Chagas disease.
AB  - There are several studies on the benefits of using TNFalpha antagonists in the
      treatment of psoriasis, but few studies addressing the interaction of these drugs
      with chronic infections. We report the case of a 52-year-old patient diagnosed
      with psoriasis refractory to traditional systemic agents, who was treated with
      biologic therapies. After one year of treatment with biologic agents, the patient
      was diagnosed with Chagas Disease. 

PMID- 26312708
TI  - Palmar and plantar lichen planus: a case report and review of the literature.
AB  - Palmoplantar lichen planus is an uncommon dermatosis. We present a case of 38
      year-old Caucasian male with a history of pruritic, scaly lesions on the right
      plantar foot. Physical examination revealed whitish plaques and numerous spiny
      hyperkeratotic papules and focal scaling. A biopsy demonstrated
      orthohyperkeratosis and acanthosis of the epidermis. Immunohistochemical staining
      revealed positivity within the epidermis and/or lichenoid infiltrate with CD3,
      CD8, CD45, CD68, myeloid histiod antigen, BCL2, p27, p53, HLA-DPDQDR,
      metallothionein and tissue inhibitor of metalloproteinases 1. The diagnosis of
      PPLP was thus confirmed; this case illustrates that PPLP should be considered in
      the differential diagnosis of uncommon foot dermatoses with a significant
      junctional inflammatory component. 

PMID- 26312709
TI  - Piloleiomyoma with segmental distribution--Case report.
AB  - Piloleiomyoma is an uncommon benign neoplasm arising from the erector pilorum
      muscle. It presents as reddish-brown papules or nodules, in general located on
      the limbs or trunk, often painful. The present paper describes a case of
      piloleiomyoma with segmental distribution on left trunk, with an important
      expression of pain. 

PMID- 26312710
TI  - Pityriasis lichenoides et varioliformis acuta after influenza vaccine.
AB  - The etiology of pityriasis lichenoides is unknown. One of the accepted theories
      admits that PL is an inflammatory response to extrinsic antigens such as
      infectious agents, drugs and vaccines. In recent medical literature, only the MMR
      vaccine (Measles, Mumps and Rubella) was associated with the occurrence of this
      disease. We present a case of a male, 12 year old healthy patient who, five days
      after Influenza vaccination, developed erythematous papules on the trunk, abdomen
      and limbs, some with adherent crusts and associated systemic symptoms. This case
      report is notable for describing the first case of pityriasis lichenoides et
      varioliformis acuta associated with the vaccine against Influenza.

PMID- 26312711
TI  - Actinic comedonal plaque-variant of Favre-Racouchot syndrome: report of two
      cases.
AB  - The actinic comedonal plaque is characterized by papules, cysts and comedones
      forming a yellowish plaque in areas of chronic sun exposure skin. There are few
      reports in literature about this entity, considered a rare and ectopic form of
      Favre-Racouchot Syndrome. We report two cases of lesions located on forearms and
      thorax. Favre-Racouchot Syndrome is a condition usually restricted to the
      periorbital area; however, there are reports of similar findings in atypical
      locations, such as forearms and chest, which are known as actinic comedonal
      plaque. Ultraviolet radiation exposure is the main factor involved in its
      pathogenesis. The objective of this study was to provide accurate knowledge of
      this dermatosis and stimulate dermatologists to provide a correct diagnosis of
      the condition. 

PMID- 26312712
TI  - Cutaneous polyarteritis nodosa.
AB  - Polyarteritis nodosa is a rare vasculitis in children characterized by
      necrotizing inflammation in small and medium size arteries. It is classified into
      systemic and cutaneous PAN according to the presence of systemic symptoms or
      visceral involvement. We describe the case of a 14-year-old girl with cutaneous
      Polyarteritis nodosa with an atypical clinical presentation. 

PMID- 26312713
TI  - Porokeratosis ptychotropica of the scrotum: dermoscopic evaluation of an atypical
      presentation.
AB  - Porokeratosis ptychotropica is a rare variant of porokeratosis that is
      classically located on the gluteal and perianal regions, seldom extending to the
      genitalia. The authors report an atypical presentation of porokeratosis
      ptychotropica and discuss the use of dermoscopy in evaluating this dermatosis.
      Dermoscopic findings, although not specific to this variant of porokeratosis, are
      helpful in the differential diagnosis of other genital disorders. Histopathology,
      through the visualization of multiple cornoid lamellae, prevails as the gold
      standard for the definite diagnosis of porokeratosis ptychotropica. 

PMID- 26312714
TI  - Linear psoriasis: case report on three year old child.
AB  - Atypical and unusual locations of psoriasis are very frequent. However, localized
      linear psoriasis is rare, with few cases described in the literature. It is
      characterized by a linear distribution of psoriasis lesions along Blaschko lines.
      We report the case of a three years old child, who presented unilateral
      erythematous scaly plaques arranged along Blaschko lines in the left hemithorax,
      with no associated symptoms and no lesions in other parts of the body. The
      differentiation of linear psoriasis from other linear dermatoses is not easy. The
      combination of a thorough history, a careful examination of the skin and
      histopathology are essential to ensure the correct diagnosis and appropriate
      treatment. 

PMID- 26312715
TI  - A case of generalized ostraceous psoriasis mimicking dermatitis neglecta.
AB  - Lithium has been implicated in the exacerbation of pre-existing psoriasis, in the
      induction of psoriasis on previously uninvolved skin of psoriasis patients, and
      in the triggering of psoriasis for the first time in patients without a personal
      or family history. Lithium-induced psoriasis (and its resistance to treatment) is
      one of the major reasons for noncompliance in patients treated with lithium. We
      describe a male patient who developed generalized ostraceous psoriasis whose
      clinical appearance mimicked dermatitis neglecta, 10 months after starting
      therapy with lithium. 

PMID- 26312716
TI  - Cheilitis granulomatosa associated with lupus erythematosus discoid and treated
      with methotrexate: report of a case.
AB  - We present the rare case of a 47-year-old patient, suffering from cheilitis
      granulomatosa and lupus erythematosus discoid: this association is really
      exceptional because only once reported in English literature. In addition, the
      treatment of cheilitis granulomatosa is a challenge for the dermatologist: the
      gold standard, represented by steroids, is in fact designed as a short-time
      option. Our report confirms the good efficacy of methotrexate as a steroid
      sparing agent.

PMID- 26312717
TI  - Complex nasal reconstruction after paracoccidioidomycosis infection--Case report.
AB  - Paracoccidioidomycosis is an infectious disease whose etiological agent belongs
      to the Paracoccidioides genus. Although it affects primarily the lungs, it can
      spread to other tissues, including the skin and mucous membranes. Despite the
      clinical treatment for this disease, scarring can produce sequelae, manifesting
      as anatomical and functional deformities of the face. We present a case of
      extensive, nasal unaesthetic and functional sequelae resulting from
      paracoccidioidomycosis, reconstructed using the paramedian forehead flap in three
      stages, through the regional unit principles. 

PMID- 26312718
TI  - Lower lip reconstruction with nasolabial flap--going back to basics.
AB  - Squamous cell carcinoma of the lower lip is frequent, and radical excision
      sometimes leads to complex defects. Many lip repair techniques are aggressive
      requiring general anesthesia and a prolonged post-operative period. The
      nasolabial flap, while a common flap for the repair of other facial defects, is
      an under-recognized option for the reconstruction of the lower lip. We describe
      the use of nasolabial flap for the repair of a large defect of the lower lip in a
      ninety year-old male, with good functional results and acceptable cosmetic
      outcome. We believe the nasolabial flap is a good alternative for intermediate-to
      large lower lip defects in patients with impaired general condition. 

PMID- 26312719
TI  - Serious stomatitis and esophagitis: a peculiar mucous reaction induced by
      pegylated liposomal doxorubicin.
AB  - Pegylated liposomal doxorubicin is an important antineoplastic agent with
      activity in a variety of solid tumors. It has a totally different profile of
      pharmacokinetics and toxicity compared with doxorubicin. It rarely causes side
      effects like cardiotoxicity or hair loss, but frequently results in many kinds of
      mucocutaneous reactions, including palmar-plantar erythrodysesthesia, diffuse
      follicular rash, intertrigo-like eruption, new formation of melanotic macules,
      stomatitis and radiation recall dermatitis. We present a rare case of multiple
      myeloma who immediately developed serious stomatitis and esophatitis associated
      with minor palmar-plantar erythrodysesthesia after a single course of pegylated
      liposomal doxorubicin. 

PMID- 26312720
TI  - Syphilis associated with paretic neurosyphilis mimicking Reiter's syndrome in HIV
      infected patients.
AB  - HIV/syphilis co-infection is common because both conditions affect similar risk
      groups. HIV interferes with the natural history of syphilis, which often has
      atypical clinical features and nervous system involvement in the early stage of
      disease. We report the case of an HIV-positive patient with secondary syphilis,
      scaling palmoplantar keratoderma, scrotal eczema, balanitis and urethritis
      mimicking Reiter's syndrome. Immunohistochemistry using polyclonal antibodies
      against Treponema pallidum revealed the presence of spirochetes, associated with
      the paretic form of parenchymal neurosyphilis. The patient was given crystalline
      penicillin, with complete resolution of dermatological and neurological symptoms,
      and no sequelae. 

PMID- 26312721
TI  - A case of secondary syphilis mimicking palmoplantar psoriasis in HIV infected
      patient.
AB  - Due to diverse clinical and histopathological presentations, diagnosis of
      secondary syphilis can occasionally prove challenging. Variable clinical
      presentations of secondary syphilis in HIV disease may result in an incorrect
      diagnosis and an inappropriate treatment regimen. Similarly, the histology of
      secondary syphilitic lesions may show considerable variation, depending on the
      clinical morphology of the eruption. We report a case of secondary syphilis in an
      HIV infected patient with cutaneous palmoplantar lesions simulating palmoplantar
      psoriasis. 

PMID- 26312722
TI  - Ehlers-Danlos Syndrome associated with cardiomyopathy hypertrophic obstructive.
AB  - Ehlers-Danlos syndrome is a rare clinical condition caused by a genetic change
      that results in the formation of structurally or functionally altered collagen.
      The clinical manifestations are varied, being the most obvious skin hypermotility
      and increased joint flexibility, although other systems - such as cardiovascular,
      respiratory and neurological - may also be affected. This paper presents the
      report of a patient who sought medical attention with complaints of atypical
      chest pain. Clinical evaluation enabled hypothetical diagnosis of hypertrophic
      obstructive cardiomyopathy and Ehlers-Danlos syndrome. Initial electrocardiogram,
      echocardiogram and 24 hours holter allowed the confirmation of the first
      hypothesis. A skin biopsy performed later associated clinical data and confirmed
      the second hypothesis. 

PMID- 26312723
TI  - Laugier-Hunziker syndrome--Case report.
AB  - Laugier-Hunziker syndrome is a rare, acquired disorder characterized by
      lenticular hyperpigmentation of the oral mucosa and longitudinal melanonychia. We
      present the case of a 63-year-old female with progressive, asymptomatic
      hyperpigmentation of buccal mucosa and a 7-year history of hyperpigmentation in
      several fingernails. Laugier-Hunziker syndrome was diagnosed based on the
      clinical features presented, dermoscopic findings and exclusion of underlying
      systemic diseases. Laugier-Hunziker syndrome is regarded as a diagnosis of
      exclusion. By identifying Laugier-Hunziker syndrome, other, more severe syndromes
      associated with hyperpigmentations can be excluded, namely Addison's disease and
      Peutz-Jeghers syndrome. 

PMID- 26312724
TI  - Rendu-Osler-Weber syndrome: dermatological approach.
AB  - The Rendu-Osler-Weber syndrome is a rare systemic fibrovascular dysplasia,
      recognized by mucocutaneous telangiectasias, arteriovenous malformations,
      epistaxis and family history. Recurrent bleeding, hypoxemia, congestive heart
      failure, portosystemic encephalopathy, and symptoms related to angiodysplasia of
      the central nervous system may occur. Since the treatment is based on supportive
      measures, early recognition is of utmost importance. This article reports the
      case of a 53-year-old male patient who presented telangiectasias on fingers, oral
      cavity and nasal mucosa for 10 years, with a history of recurrent epistaxis of
      varying severity since childhood. Mother, sister and daughter have similar
      lesions. 

PMID- 26312725
TI  - Stewart Treves Syndrome.
AB  - Stewart-Treves Syndrome is characterized by the presence of lymphangiosarcoma on
      limb extremities. Rare, it occurs in 0.5% of patients who have undergone radical
      mastectomy with axillary node dissection. The main cause is chronic lymphedema
      with endothelial and lymphatic differentiation, with no direct relationship to
      breast cancer. Seven years after a radical right-side mastectomy with lymph node
      dissection and adjuvant therapy, the patient developed a lesion on her right arm.
      The dermatological examination revealed an erythematous nodule with bleeding
      surface on chronic right forearm lymphedema. After the biopsy, a
      lymphangiosarcoma on chronic lymphedema was diagnosed. Infrequent, this syndrome
      is relevant because of its associated mortality. Early diagnosis is important to
      improve survival and reduce complications. 

PMID- 26312726
TI  - Stewart-Treves Syndrome of the Lower Extremity.
AB  - Stewart-Treves syndrome is a rare cutaneous angiosarcoma that develops in long
      standing chronic lymphedema. Though most commonly this angiosarcoma is a result
      of post mastectomy lymphoedema, it also develops in Milroy disease, idiopathic,
      congenital, traumatic and filarial lymphoedema. Despite the rarity of this
      syndrome and its poor prognosis, early diagnosis associated with radical surgery
      can provide improved survival. We report a case of angiosarcoma in the lower limb
      in a patient with chronic lymphedema associated with history of repeated
      erysipela episodes. 

PMID- 26312727
TI  - Solitary eccrine syringofibroadenoma--Case Report.
AB  - Eccrine syringofibroadenoma is a rare benign adnexal neoplasm derived from cells
      of the acrosyringium of eccrine sweat glands. ESFA usually manifests as a
      solitary nodule on the extremities of elderly patients, but it may also present
      as papules, nodules or plaques. Its clinical appearance is nonspecific and
      malignant neoplasms should be considered in the differential diagnosis. However,
      histopathological findings are typical. The main treatment is surgical excision.
      In order to illustrate a typical presentation of the tumor, we report a case of
      solitary eccrine syringofibroadenoma, including the surgical treatment used and
      its result.

PMID- 26312728
TI  - Late-onset of eruptive syringomas: a diagnostic challenge.
AB  - Syringoma is a benign, adnexal tumor of the eccrine sweat gland ducts. Eruptive
      syringomas are a rare variant, occurring before or during puberty in most cases.
      A 57-year-old man was observed in our department, with a 10-year history of
      multiple brownish papules (1-4mm in diameter), localized on the neck, shoulders,
      trunk and axillae. The clinical diagnosis was cutaneous mastocytosis.
      Histopathological examination from a papule in the trunk was compatible with the
      diagnosis of syringoma. The patient was treated with isotretinoin, without any
      improvement. The clinical diagnosis of eruptive syringoma is difficult and
      histological examination is crucial for its diagnosis. Long-term morbidity is not
      associated with syringomas; they are treated for cosmetic reasons with
      unsatisfactory results.

PMID- 26312729
TI  - Vemurafenib and cutaneous adverse events--report of five cases.
AB  - Vemurafenib is a selective inhibitor of V600E-mutant BRAF protein used to treat
      metastatic and unresectable melanoma. Clinical trials have shown increased
      overall survival and progression-free survival in patients treated with
      Vemurafenib. However, cutaneous adverse events are common during treatment. We
      report fi ve cases of metastatic melanoma with BRAF V600E positivity, treated
      with Vemurafenib and its cutaneous adverse events. Dermatologists and oncologists
      need to be aware of possible skin changes caused by this medication, which is
      increasingly employed in melanoma treatment. Monitoring of patients during
      therapy is important for early treatment of adverse cutaneous cutaneous adverse
      events, improvement in quality of life and adherence to treatment. 

PMID- 26312730
TI  - Nanomedicine Applications of Hybrid Nanomaterials Built from Metal-Ligand
      Coordination Bonds: Nanoscale Metal-Organic Frameworks and Nanoscale Coordination
      Polymers.

PMID- 26312731
TI  - A molecular theory for optimal blue energy extraction by electrical double layer
      expansion.
AB  - Electrical double layer expansion (CDLE) has been proposed as a promising
      alternative to reverse electrodialysis (RED) and pressure retarded osmosis (PRO)
      processes for extracting osmotic power generated by the salinity difference
      between freshwater and seawater. The performance of the CDLE process is sensitive
      to the configuration of porous electrodes and operation parameters for ion
      extraction and release cycles. In this work, we use a classical density
      functional theory (CDFT) to examine how the electrode pore size and
      charging/discharging potentials influence the thermodynamic efficiency of the
      CDLE cycle. The existence of an optimal charging potential that maximizes the
      energy output for a given pore configuration is predicted, which varies
      substantially with the pore size, especially when it is smaller than 2 nm. The
      thermodynamic efficiency is maximized when the electrode has a pore size about
      twice the ion diameter. 

PMID- 26312732
TI  - Nanoscale Confinement of All-Optical Magnetic Switching in TbFeCo--Competition
      with Nanoscale Heterogeneity.
AB  - Single femtosecond optical laser pulses, of sufficient intensity, are
      demonstrated to reverse magnetization in a process known as all-optical
      switching. Gold two-wire antennas are placed on the all-optical switching film
      TbFeCo. These structures are resonant with the optical field, and they create a
      field enhancement in the near-field which confines the area where optical
      switching can occur. The magnetic switching that occurs around and below the
      antenna is imaged using resonant X-ray holography and magnetic circular
      dichroism. The results not only show the feasibility of controllable switching
      with antenna assistance but also demonstrate the highly inhomogeneous nature of
      the switching process, which is attributed to the process depending on the
      material's heterogeneity. 

PMID- 26312734
TI  - Role of substituents on the reactivity and product selectivity in reactions of
      naphthalene derivatives catalyzed by the orphan thermostable cytochrome P450,
      CYP175A1.
AB  - The thermostable nature of CYP175A1 enzyme is of potential interest for the
      biocatalysis at ambient temperature or at elevated temperature under
      environmentally benign conditions. Although little is known about the substrate
      selectivity of this enzyme, the biocatalytic activities of CYP175A1 on different
      substituted naphthalenes have been studied in oxidative pathway, and the effect
      of the substituent on the reaction has been determined. The enzyme first acts as
      a peroxygenase to convert these substituted naphthalenes to the corresponding
      naphthols, which subsequently undergo in-situ oxidative dimerization to form dyes
      of different colors possibly by the peroxidase-type activity of CYP175A1. The
      product analyses and kinetic measurements suggested that the presence of electron
      releasing substituent (ERS) in the substrate enhanced the substrate conversion,
      whereas the presence of electron withdrawing substituent (EWS) in the substrate
      drastically reduced the substrate conversion. The position of the ERS in the
      substrate was also found to play an important role in the transformation of the
      substrate. The results further demonstrate that mutation of the Leu80 residue to
      Phe enhances the reactivity of the enzyme by favoring the substrate association
      in the active site. The observed rates of the enzymatic oxygenation reaction of
      the substituted naphthalenes followed the Hammett correlation of substituent
      effect, supporting aromatic electrophilic substitution mechanism catalyzed by the
      cytochrome P450 enzyme. 

PMID- 26312735
TI  - A new method of detecting changes in corneal health in response to toxic insults.
AB  - The size and arrangement of stromal collagen fibrils (CFs) influence the optical
      properties of the cornea and hence its function. The spatial arrangement of the
      collagen is still questionable in relation to the diameter of collagen fibril. In
      the present study, we introduce a new parameter, edge-fibrillar distance (EFD) to
      measure how two collagen fibrils are spaced with respect to their closest edges
      and their spatial distribution through normalized standard deviation of EFD
      (NSDEFD) accessed through the application of two commercially available
      multipurpose solutions (MPS): ReNu and Hippia. The corneal buttons were soaked
      separately in ReNu and Hippia MPS for five hours, fixed overnight in 2.5%
      glutaraldehyde containing cuprolinic blue and processed for transmission electron
      microscopy. The electron micrographs were processed using ImageJ user-coded
      plugin. Statistical analysis was performed to compare the image processed
      equivalent diameter (ED), inter-fibrillar distance (IFD), and EFD of the CFs of
      treated versus normal corneas. The ReNu-soaked cornea resulted in partly
      degenerated epithelium with loose hemidesmosomes and Bowman's collagen. In
      contrast, the epithelium of the cornea soaked in Hippia was degenerated or lost
      but showed closely packed Bowman's collagen. Soaking the corneas in both MPS
      caused a statistically significant decrease in the anterior collagen fibril, ED
      and a significant change in IFD, and EFD than those of the untreated corneas
      (p<0.05, for all comparisons). The introduction of EFD measurement in the study
      directly provided a sense of gap between periphery of the collagen bundles, their
      spatial distribution; and in combination with ED, they showed how the corneal
      collagen bundles are spaced in relation to their diameters. The spatial
      distribution parameter NSDEFD indicated that ReNu treated cornea fibrils were
      uniformly distributed spatially, followed by normal and Hippia. The EFD
      measurement with relatively lower standard deviation and NSDEFD, a characteristic
      of uniform CFs distribution, can be an additional parameter used in evaluating
      collagen organization and accessing the effects of various treatments on corneal
      health and transparency. 

PMID- 26312736
TI  - Design, synthesis and 1H NMR study of C3v-symmetric anion receptors with urethane
      NH as recognition group.
AB  - C3v-Symmetric anion receptors 3 and 4 with urethane groups were synthesized by
      using trindane triol as tripodal molecular framework. In (1)H NMR titration
      study, the receptors showed noticeable downfield shift/disappearance of the
      urethane-NH peak in presence of H2PO4(-) and F(-) due to the host-guest
      complexation occurred through multiple hydrogen bonding and/or the deprotonation
      of urethane-NH groups. Other tested anions such as Cl(-), Br(-), HSO4(-), and
      NO3(-) showed either no or negligible chemical shift of the urethane groups. The
      deprotonation event in 4 allowed selective detection of F(-) by perceptible color
      change from colorless to yellowish-red with the appearance of a new charge
      transfer absorption band at 450 nm.

PMID- 26312737
TI  - Microwave-assisted ultrafast synthesis of silver nanoparticles for detection of
      Hg2+.
AB  - Silver nanoparticles (AgNPs) were successfully prepared in aqueous solution by a
      one-pot procedure based on a rapid microwave-assisted green approach. L-Cysteine
      acted as a capping agent in the process of AgNP formation. The structural and
      morphological characteristics of the L-cysteine-capped AgNPs were investigated by
      the UV-vis, CD, FL, FTIR, XRD, TEM and EDX analysis. It was found that the well
      dispersed crystalline AgNPs were formed after irradiation for 90 s and had sphere
      like morphology. Such strategy may facilitate new ways to the synthesis of other
      metal nanoparticles, such as Au, Pt and Pd. In addition, the synthesized AgNPs
      were developed as a platform for the detection of Hg(2+) and showed a high
      sensitivity on the order of 1*10(-8) M. This sensing system could discriminate
      Hg(2+) from a wide range of cations (Ca(2+), Ba(2+), Mn(2+), etc.). The
      selectivity and sensitivity of AgNPs indicated its potential use as a sensor for
      Hg(2+) detection in the ecosystems.

PMID- 26312738
TI  - Development of new UV-vis spectroscopic microwave-assisted method for
      determination of glucose in pharmaceutical samples.
AB  - A new UV-Visible spectroscopic method assisted with microwave for the
      determination of glucose in pharmaceutical formulations was developed. In this
      study glucose solutions were oxidized by ammonium molybdate in the presence of
      microwave energy and reacted with aniline to produce a colored solution. Optimum
      conditions of the reaction including wavelength, temperature, and pH of the
      medium and relative concentration ratio of the reactants were investigated. It
      was found that the optimal wavelength for the reaction is 610 nm, the optimal
      reaction time is 80s, the optimal reaction temperature is 160 degrees C, the
      optimal reaction pH is 4, and the optimal concentration ratio aniline/ammonium
      molybdate solution was found to be 1:1. The limits of detection and
      quantification of the method are 0.82 and 2.75 ppm for glucose solution,
      respectively. The use of microwaves improved the speed of the method while the
      use of aniline improved the sensitivity of the method by shifting the wavelength.

PMID- 26312739
TI  - Theoretical and experimental NMR studies on muscimol from fly agaric mushroom
      (Amanita muscaria).
AB  - In this article we report results of combined theoretical and experimental NMR
      studies on muscimol, the bioactive alkaloid from fly agaric mushroom (Amanita
      muscaria). The assignment of (1)H and (13)C NMR spectra of muscimol in DMSO-d6
      was supported by additional two-dimensional heteronuclear correlated spectra (2D
      NMR) and gauge independent atomic orbital (GIAO) NMR calculations using density
      functional theory (DFT). The effect of solvent in theoretical calculations was
      included via polarized continuum model (PCM) and the hybrid three-parameter B3LYP
      density functional in combination with 6-311++G(3df,2pd) basis set enabled
      calculation of reliable structures of non-ionized (neutral) molecule and its NH
      and zwitterionic forms in the gas phase, chloroform, DMSO and water. GIAO NMR
      calculations, using equilibrium and rovibrationally averaged geometry, at B3LYP/6
      31G* and B3LYP/aug-cc-pVTZ-J levels of theory provided muscimol nuclear magnetic
      shieldings. The theoretical proton and carbon chemical shifts were critically
      compared with experimental NMR spectra measured in DMSO. Our results provide
      useful information on its structure in solution. We believe that such data could
      improve the understanding of basic features of muscimol at atomistic level and
      provide another tool in studies related to GABA analogs. 

PMID- 26312740
TI  - Melting Himalayan glaciers contaminated by legacy atmospheric depositions are
      important sources of PCBs and high-molecular-weight PAHs for the Ganges
      floodplain during dry periods.
AB  - Melting glaciers are natural redistributors of legacy airborne pollutants,
      affecting exposure of pristine proglacial environments. Our data shows that
      melting Himalayan glaciers can be major contributors of polychlorinated biphenyls
      (PCBs) and high-molecular-weight polycyclic aromatic hydrocarbons (PAHs) for
      surface water in the Gangetic Plain during the dry season. Glacial emissions can
      exceed in some cases inputs from diffuse sources within the catchment. We
      analyzed air, deposition and river water in several sections along the Ganges
      River and its major headwaters. The predominant glacial origin of these
      contaminants in the Himalayan reach was demonstrated using air-water fugacity
      ratios and mass balance analysis. The proportion of meltwater emissions compared
      to pollutant discharge at downstream sections in the central part of the Gangetic
      Plain was between 2 and 200%. By remobilizing legacy pollutants from melting
      glaciers, climate change can enhance exposure levels over large and already
      heavily impacted regions of Northern India. 

PMID- 26312741
TI  - Microplastic in three urban estuaries, China.
AB  - Estuarine Microplastics (MPs) are limited to know globally. By filtering
      subsurface water through 330 MUm nets, MPs in Jiaojiang, Oujiang Estuaries were
      quantified, as well as that in Minjiang Estuary responding to Typhoon Soulik.
      Polymer matrix was analyzed by Raman spectroscopy. MP (<5 mm) comprised more than
      90% of total number plastics. The highest MPs density was found in Minjiang,
      following Jiaojiang and Oujiang. Fibers and granules were the primary shapes,
      with no pellets found. Colored MPs were the majority. The concentrations of
      suspended microplastics determine their bioavailability to low trophic organisms,
      and then possibly promoting the transfer of microplastic to higher trophic
      levels. Polypropylene and polyethylene were the prevalent types of MPs analyzed.
      Economic structures in urban estuaries influenced on MPs contamination levels.
      Typhoon didn't influence the suspended MP densities significantly. Our results
      provide basic information for better understanding suspended microplastics within
      urban estuaries and for managerial actions. 

PMID- 26312742
TI  - Litter mercury deposition in the Amazonian rainforest.
AB  - The objective of this work was to assess the flux of atmospheric mercury
      transferred to the soil of the Amazonian rainforest by litterfall. Calculations
      were based on a large survey of published and unpublished data on litterfall and
      Hg concentrations in litterfall samples from the Amazonian region. Litterfall
      based on 65 sites located in the Amazon rainforest averaged 8.15 +/- 2.25 Mg ha(
      1) y(-1). Average Hg concentrations were calculated from nine datasets for fresh
      tree leaves and ten datasets for litter, and a median concentration of 60.5 ng Hg
      g(-1) was considered for Hg deposition in litterfall, which averaged 49 +/- 14
      MUg m(-2) yr(-1). This value was used to estimate that in the Amazonian
      rainforest, litterfall would be responsible for the annual removing of 268 +/- 77
      Mg of Hg, approximately 8% of the total atmospheric Hg deposition to land. The
      impact of the Amazon deforestation on the Hg biogeochemical cycle is also
      discussed. 

PMID- 26312743
TI  - Hexabromocyclododecane flame retardant in Antarctica: Research stations as
      sources.
AB  - Historical persistent organic pollutants (POPs) are banned from Antarctica under
      international treaty; but contemporary-use POPs can enter as additives within
      polymer and textile products. Over their useful lives these products may release
      additives in-situ. Indeed, we observed 226 and 109 ng/g dry weight (dw) of the
      total concentrations of alpha-, beta- and gamma-hexabromocyclododecane (HBCD) in
      indoor dust from McMurdo Station (U.S.) and Scott Station (New Zealand),
      respectively. Sewage sludge collected from wastewater treatment facilities at
      these stations exhibited ?HBCD of 45 and 69 ng/g dw, respectively. Contaminants
      originally within the bases may exit to the local outdoor environment via
      wastewaters. Near McMurdo, maximum ?HBCD levels in surficial marine sediments and
      aquatic biota (invertebrates and fish) were 2350 ng/g (total organic carbon
      basis) and 554 ng/g lipid weight, respectively. Levels declined with distance
      from McMurdo. Our results illustrate that Antarctic research stations serve as
      local HBCD sources to the pristine Antarctic environment. 

PMID- 26312744
TI  - Polymer-Controlled Morphosynthesis and Mineralization of Metal Carbonate
      Superstructures (?).
AB  - Different morphosynthesis strategies for various metal carbonate minerals such as
      CaCO3, BaCO3, CdCO3, MnCO3, and PbCO3 using double hydrophilic block copolymers
      (DHBCs) as crystal modifiers are presented. The influence of the DHBCs with
      different functionalities such as carboxyl, partially phosphonated, and
      phosphorylated groups on the crystallization and structure formation was
      investigated. Well-defined crystals with size range from mesoscale to microscale
      can be easily obtained. More complex higher-order superstructures such as hollow
      spheres and big spherules with controlled surface structures can also be
      assembled conveniently. The results show that polymer-controlled mineralization
      is a versatile tool toward crystal morphogenesis. A time-dependent self-assembly
      and growth of "sphere-to-rod-to-dumbbell-to-sphere" structures was observed in
      the case of BaCO3 under the control of DHBCs, adding to the already reported
      examples of CaCO3 and fluoroapatite. In addition, we found that the influence of
      the DHBCs while increasing the ionic strength was lost in case of CaCO3, implying
      that the strong selective interaction between the functional groups of DHBCs and
      crystals has electrostatic contributions. 

PMID- 26312745
TI  - Ab Initio Prediction of Piezoelectricity in Two-Dimensional Materials.
AB  - Two-dimensional (2D) materials present many unique materials concepts, including
      material properties that sometimes differ dramatically from those of their bulk
      counterparts. One of these properties, piezoelectricity, is important for micro-
      and nanoelectromechanical systems applications. Using symmetry analysis, we
      determine the independent piezoelectric coefficients for four groups of predicted
      and synthesized 2D materials. We calculate with density-functional perturbation
      theory the stiffness and piezoelectric tensors of these materials. We determine
      the in-plane piezoelectric coefficient d11 for 37 materials within the families
      of 2D metal dichalcogenides, metal oxides, and III-V semiconductor materials. A
      majority of the structures, including CrSe2, CrTe2, CaO, CdO, ZnO, and InN, have
      d11 coefficients greater than 5 pm/V, a typical value for bulk piezoelectric
      materials. Our symmetry analysis shows that buckled 2D materials exhibit an out
      of-plane coefficient d31. We find that d31 for 8 III-V semiconductors ranges from
      0.02 to 0.6 pm/V. From statistical analysis, we identify correlations between the
      piezoelectric coefficients and the electronic and structural properties of the 2D
      materials that elucidate the origin of the piezoelectricity. Among the 37 2D
      materials, CdO, ZnO, and CrTe2 stand out for their combination of large
      piezoelectric coefficient and low formation energy and are recommended for
      experimental exploration. 

PMID- 26312746
TI  - alpha-NaYb(Mn)F4:Er(3+)/Tm(3+)@NaYF4 UCNPs as "Band-Shape" Luminescent
      Nanothermometers over a Wide Temperature Range.
AB  - Novel flower-like alpha-NaYb(Mn)F4:Er(3+)/Tm(3+)@NaYF4 upconversion nanoparticles
      (UCNPs) as luminescent nanothermometers have been developed by combining liquid
      solid solution hydrothermal strategy with thermal decomposition strategy. Under
      980 nm excitation, they exhibit intense upconversion luminescence and temperature
      dependent upconversion luminescence over a wide temperature range. The influence
      of temperature on "band-shape" upconversion luminescence (UCL) spectra and the
      intensity of emission bands are analyzed and discussed in detail. We further
      successfully test and verify that intensity ratios REr of (2)H11/2 -> (4)I15/2
      and (4)S3/2 -> (4)I15/2 and RTm of (1)G4 -> (3)H5 and (3)H4 -> (3)H6 are
      sensitive to temperature, and the population of active ions follows Boltzmann
      type population distribution very well. These luminescent nanothermometers could
      be applied over a wide temperature range from 123 to 423 K with high sensitivity,
      which enable them to be excellent candidates for temperature sensors. 

PMID- 26312747
TI  - A Novel Prime and Boost Regimen of HIV Virus-Like Particles with TLR4 Adjuvant
      MPLA Induces Th1 Oriented Immune Responses against HIV.
AB  - HIV virus-like particles (VLPs) present the HIV envelope protein in its native
      conformation, providing an ideal vaccine antigen. To enhance the immunogenicity
      of the VLP vaccine, we sought to improve upon two components; the route of
      administration and the additional adjuvant. Using HIV VLPs, we evaluated sub
      cheek as a novel route of vaccine administration when combined with other
      conventional routes of immunization. Of five combinations of distinct prime and
      boost sequences, which included sub-cheek, intranasal, and intradermal routes of
      administration, intranasal prime and sub-cheek boost (IN+SC) resulted in the
      highest HIV-specific IgG titers among the groups tested. Using the IN+SC regimen
      we tested the adjuvant VesiVax Conjugatable Adjuvant Lipid Vesicles (CALV) +
      monophosphoryl lipid A (MPLA) at MPLA concentrations of 0, 7.5, 12.5, and 25
      MUg/dose in combination with our VLPs. Mice that received 12.5 or 25 MUg/dose
      MPLA had the highest concentrations of Env-specific IgG2c (20.7 and 18.4 MUg/ml
      respectively), which represents a Th1 type of immune response in C57BL/6 mice.
      This was in sharp contrast to mice which received 0 or 7.5 MUg MPLA adjuvant
      (6.05 and 5.68 MUg/ml of IgG2c respectively). In contrast to IgG2c, MPLA had
      minor effects on Env-specific IgG1; therefore, 12.5 and 25 MUg/dose of MPLA
      induced the optimal IgG1/IgG2c ratio of 1.3. Additionally, the percentage of
      germinal center B cells increased significantly from 15.4% in the control group
      to 31.9% in the CALV + 25 MUg MPLA group. These mice also had significantly more
      IL-2 and less IL-4 Env-specific CD8+ T cells than controls, correlating with an
      increased percentage of Env-specific central memory CD4+ and CD8+ T cells. Our
      study shows the strong potential of IN+SC as an efficacious route of
      administration and the effectiveness of VLPs combined with MPLA adjuvant to
      induce Env specific Th1-oriented HIV-specific immune responses. 

PMID- 26312748
TI  - Genetic Differentiation in Insular Lowland Rainforests: Insights from Historical
      Demographic Patterns in Philippine Birds.
AB  - Phylogeographic studies of Philippine birds support that deep genetic structure
      occurs across continuous lowland forests within islands, despite the lack of
      obvious contemporary isolation mechanisms. To examine the pattern and tempo of
      diversification within Philippine island forests, and test if common mechanisms
      are responsible for observed differentiation, we focused on three co-distributed
      lowland bird taxa endemic to Greater Luzon and Greater Negros-Panay: Blue-headed
      Fantail (Rhipidura cyaniceps), White-browed Shama (Copsychus luzoniensis), and
      Lemon-throated Leaf-Warbler (Phylloscopus cebuensis). Each species has two
      described subspecies within Greater Luzon, and a single described subspecies on
      Greater Negros/Panay. Each of the three focal species showed a common geographic
      pattern of two monophyletic groups in Greater Luzon sister to a third
      monophyletic group found in Greater Negros-Panay, suggesting that common or
      similar biogeographic processes may have produced similar distributions. However,
      studied species displayed variable levels of mitochondrial DNA differentiation
      between clades, and genetic differentiation within Luzon was not necessarily
      concordant with described subspecies boundaries. Population genetic parameters
      for the three species suggested both rapid population growth from small numbers
      and geographic expansion across Luzon Island. Estimates of the timing of
      population expansion further supported that these events occurred asynchronously
      throughout the Pleistocene in the focal species, demanding particular
      explanations for differentiation, and support that co-distribution may be
      secondarily congruent.

PMID- 26312750
TI  - Correction: Latent Autoimmune Diabetes in Adults in the United Arab Emirates:
      Clinical Features and Factors Related to Insulin-Requirement.

PMID- 26312749
TI  - Unraveling Comparative Anti-Amyloidogenic Behavior of Pyrazinamide and D
      Cycloserine: A Mechanistic Biophysical Insight.
AB  - Amyloid fibril formation by proteins leads to variety of degenerative disorders
      called amyloidosis. While these disorders are topic of extensive research,
      effective treatments are still unavailable. Thus in present study, two anti
      tuberculosis drugs, i.e., pyrazinamide (PYZ) and D-cycloserine (DCS), also known
      for treatment for Alzheimer's dementia, were checked for the anti-aggregation and
      anti-amyloidogenic ability on Abeta-42 peptide and hen egg white lysozyme.
      Results demonstrated that both drugs inhibit the heat induced aggregation;
      however, PYZ was more potent and decelerated the nucleation phase as observed
      from various spectroscopic and microscopic techniques. Furthermore, pre-formed
      amyloid fibrils incubated with these drugs also increased the PC12/SH-SY5Y cell
      viability as compare to the amyloid fibrils alone; however, the increase was more
      pronounced for PYZ as confirmed by MTT assay. Additionally, molecular docking
      study suggested that the greater inhibitory potential of PYZ as compare to DCS
      may be due to strong binding affinity and more occupancy of hydrophobic patches
      of HEWL, which is known to form the core of the protein fibrils. 

PMID- 26312751
TI  - Systemic EP4 Inhibition Increases Adhesion Formation in a Murine Model of Flexor
      Tendon Repair.
AB  - Flexor tendon injuries are a common clinical problem, and repairs are frequently
      complicated by post-operative adhesions forming between the tendon and
      surrounding soft tissue. Prostaglandin E2 and the EP4 receptor have been
      implicated in this process following tendon injury; thus, we hypothesized that
      inhibiting EP4 after tendon injury would attenuate adhesion formation. A model of
      flexor tendon laceration and repair was utilized in C57BL/6J female mice to
      evaluate the effects of EP4 inhibition on adhesion formation and matrix
      deposition during flexor tendon repair. Systemic EP4 antagonist or vehicle
      control was given by intraperitoneal injection during the late proliferative
      phase of healing, and outcomes were analyzed for range of motion, biomechanics,
      histology, and genetic changes. Repairs treated with an EP4 antagonist
      demonstrated significant decreases in range of motion with increased resistance
      to gliding within the first three weeks after injury, suggesting greater adhesion
      formation. Histologic analysis of the repair site revealed a more robust
      granulation zone in the EP4 antagonist treated repairs, with early polarization
      for type III collagen by picrosirius red staining, findings consistent with
      functional outcomes. RT-PCR analysis demonstrated accelerated peaks in F4/80 and
      type III collagen (Col3a1) expression in the antagonist group, along with
      decreases in type I collagen (Col1a1). Mmp9 expression was significantly
      increased after discontinuing the antagonist, consistent with its role in
      mediating adhesion formation. Mmp2, which contributes to repair site remodeling,
      increases steadily between 10 and 28 days post-repair in the EP4 antagonist
      group, consistent with the increased matrix and granulation zones requiring
      remodeling in these repairs. These findings suggest that systemic EP4 antagonism
      leads to increased adhesion formation and matrix deposition during flexor tendon
      healing. Counter to our hypothesis that EP4 antagonism would improve the healing
      phenotype, these results highlight the complex role of EP4 signaling during
      tendon repair. 

PMID- 26312752
TI  - High-Throughput All-Optical Analysis of Synaptic Transmission and Synaptic
      Vesicle Recycling in Caenorhabditis elegans.
AB  - Synaptic vesicles (SVs) undergo a cycle of biogenesis and membrane fusion to
      release transmitter, followed by recycling. How exocytosis and endocytosis are
      coupled is intensively investigated. We describe an all-optical method for
      identification of neurotransmission genes that can directly distinguish SV
      recycling factors in C. elegans, by motoneuron photostimulation and muscular
      RCaMP Ca2+ imaging. We verified our approach on mutants affecting synaptic
      transmission. Mutation of genes affecting SV recycling (unc-26 synaptojanin, unc
      41 stonin, unc-57 endophilin, itsn-1 intersectin, snt-1 synaptotagmin) showed a
      distinct 'signature' of muscle Ca2+ dynamics, induced by cholinergic motoneuron
      photostimulation, i.e. faster rise, and earlier decrease of the signal,
      reflecting increased synaptic fatigue during ongoing photostimulation. To
      facilitate high throughput, we measured (3-5 times) ~1000 nematodes for each
      gene. We explored if this method enables RNAi screening for SV recycling genes.
      Previous screens for synaptic function genes, based on behavioral or
      pharmacological assays, allowed no distinction of the stage of the SV cycle in
      which a protein might act. We generated a strain enabling RNAi specifically only
      in cholinergic neurons, thus resulting in healthier animals and avoiding lethal
      phenotypes resulting from knockdown elsewhere. RNAi of control genes resulted in
      Ca2+ measurements that were consistent with results obtained in the respective
      genomic mutants, albeit to a weaker extent in most cases, and could further be
      confirmed by opto-electrophysiological measurements for mutants of some of the
      genes, including synaptojanin. We screened 95 genes that were previously
      implicated in cholinergic transmission, and several controls. We identified genes
      that clustered together with known SV recycling genes, exhibiting a similar
      signature of their Ca2+ dynamics. Five of these genes (C27B7.7, erp-1, inx-8, inx
      10, spp-10) were further assessed in respective genomic mutants; however, while
      all showed electrophysiological phenotypes indicative of reduced cholinergic
      transmission, no obvious SV recycling phenotypes could be uncovered for these
      genes. 

PMID- 26312753
TI  - Different Mechanisms of Regulation of the Warburg Effect in Lymphoblastoid and
      Burkitt Lymphoma Cells.
AB  - BACKGROUND: The Warburg effect is one of the hallmarks of cancer and rapidly
      proliferating cells. It is known that the hypoxia-inducible factor 1-alpha
      (HIF1A) and MYC proteins cooperatively regulate expression of the HK2 and PDK1
      genes, respectively, in the Burkitt lymphoma (BL) cell line P493-6, carrying an
      inducible MYC gene repression system. However, the mechanism of aerobic
      glycolysis in BL cells has not yet been fully understood. METHODS AND FINDINGS:
      Western blot analysis showed that the HIF1A protein was highly expressed in
      Epstein-Barr virus (EBV)-positive BL cell lines. Using biochemical assays and
      quantitative PCR (Q-PCR), we found that-unlike in lymphoblastoid cell lines
      (LCLs)-the MYC protein was the master regulator of the Warburg effect in these BL
      cell lines. Inhibition of the transactivation ability of MYC had no influence on
      aerobic glycolysis in LCLs, but it led to decreased expression of MYC-dependent
      genes and lactate dehydrogenase A (LDHA) activity in BL cells. CONCLUSIONS: Our
      data suggest that aerobic glycolysis, or the Warburg effect, in BL cells is
      regulated by MYC expressed at high levels, whereas in LCLs, HIF1A is responsible
      for this phenomenon.

PMID- 26312754
TI  - The Effect of Thermophoresis on Unsteady Oldroyd-B Nanofluid Flow over Stretching
      Surface.
AB  - There are currently only a few theoretical studies on convective heat transfer in
      polymer nanocomposites. In this paper, the unsteady incompressible flow of a
      polymer nanocomposite represented by an Oldroyd-B nanofluid along a stretching
      sheet is investigated. Recent studies have assumed that the nanoparticle fraction
      can be actively controlled on the boundary, similar to the temperature. However,
      in practice, such control presents significant challenges and in this study the
      nanoparticle flux at the boundary surface is assumed to be zero. We have used a
      relatively novel numerical scheme; the spectral relaxation method to solve the
      momentum, heat and mass transport equations. The accuracy of the solutions has
      been determined by benchmarking the results against the quasilinearisation
      method. We have conducted a parametric study to determine the influence of the
      fluid parameters on the heat and mass transfer coefficients. 

PMID- 26312755
TI  - Distinct Actin and Lipid Binding Sites in Ysc84 Are Required during Early Stages
      of Yeast Endocytosis.
AB  - During endocytosis in S. cerevisiae, actin polymerization is proposed to provide
      the driving force for invagination against the effects of turgor pressure. In
      previous studies, Ysc84 was demonstrated to bind actin through a conserved N
      terminal domain. However, full length Ysc84 could only bind actin when its C
      terminal SH3 domain also bound to the yeast WASP homologue Las17. Live cell
      imaging has revealed that Ysc84 localizes to endocytic sites after Las17/WASP but
      before other known actin binding proteins, suggesting it is likely to function at
      an early stage of membrane invagination. While there are homologues of Ysc84 in
      other organisms, including its human homologue SH3yl-1, little is known of its
      mode of interaction with actin or how this interaction affects actin filament
      dynamics. Here we identify key residues involved both in Ysc84 actin and lipid
      binding, and demonstrate that its actin binding activity is negatively regulated
      by PI(4,5)P2. Ysc84 mutants defective in their lipid or actin-binding interaction
      were characterized in vivo. The abilities of Ysc84 to bind Las17 through its C
      terminal SH3 domain, or to actin and lipid through the N-terminal domain were all
      shown to be essential in order to rescue temperature sensitive growth in a strain
      requiring YSC84 expression. Live cell imaging in strains with fluorescently
      tagged endocytic reporter proteins revealed distinct phenotypes for the mutants
      indicating the importance of these interactions for regulating key stages of
      endocytosis. 

PMID- 26312757
TI  - Single layer lead iodide: computational exploration of structural, electronic and
      optical properties, strain induced band modulation and the role of spin-orbital
      coupling.
AB  - Graphitic like layered materials exhibit intriguing electronic structures and
      thus the search for new types of two-dimensional (2D) monolayer materials is of
      great interest for developing novel nano-devices. By using density functional
      theory (DFT) method, here we for the first time investigate the structure,
      stability, electronic and optical properties of monolayer lead iodide (PbI2). The
      stability of PbI2 monolayer is first confirmed by phonon dispersion calculation.
      Compared to the calculation using generalized gradient approximation, screened
      hybrid functional and spin-orbit coupling effects can not only predicts an
      accurate bandgap (2.63 eV), but also the correct position of valence and
      conduction band edges. The biaxial strain can tune its bandgap size in a wide
      range from 1 eV to 3 eV, which can be understood by the strain induced uniformly
      change of electric field between Pb and I atomic layer. The calculated imaginary
      part of the dielectric function of 2D graphene/PbI2 van der Waals type hetero
      structure shows significant red shift of absorption edge compared to that of a
      pure monolayer PbI2. Our findings highlight a new interesting 2D material with
      potential applications in nanoelectronics and optoelectronics. 

PMID- 26312756
TI  - Of Fighting Flies, Mice, and Men: Are Some of the Molecular and Neuronal
      Mechanisms of Aggression Universal in the Animal Kingdom?
AB  - Aggressive behavior is widespread in the animal kingdom, but the degree of
      molecular conservation between distantly related species is still unclear. Recent
      reports suggest that at least some of the molecular mechanisms underlying this
      complex behavior in flies show remarkable similarities with such mechanisms in
      mice and even humans. Surprisingly, some aspects of neuronal control of
      aggression also show remarkable similarity between these distantly related
      species. We will review these recent findings, address the evolutionary
      implications, and discuss the potential impact for our understanding of human
      diseases characterized by excessive aggression. 

PMID- 26312759
TI  - Correction: A shock tube study of the branching ratios of propene + OH reaction.
AB  - Correction for 'A shock tube study of the branching ratios of propene + OH
      reaction' by Jihad Badra et al., Phys. Chem. Chem. Phys., 2015, 17, 2421-2431. 

PMID- 26312758
TI  - Enriched Environment Protects the Optic Nerve from Early Diabetes-Induced Damage
      in Adult Rats.
AB  - Diabetic retinopathy is a leading cause of reduced visual acuity and acquired
      blindness. Axoglial alterations of the distal (close to the chiasm) optic nerve
      (ON) could be the first structural change of the visual pathway in streptozotocin
      (STZ)-induced diabetes in rats. We analyzed the effect of environmental
      enrichment on axoglial alterations of the ON provoked by experimental diabetes.
      For this purpose, three days after vehicle or STZ injection, animals were housed
      in enriched environment (EE) or remained in a standard environment (SE) for 6
      weeks. Anterograde transport, retinal morphology, optic nerve axons (toluidine
      blue staining and phosphorylated neurofilament heavy immunoreactivity),
      microglia/macrophages (ionized calcium binding adaptor molecule 1 (Iba-1)
      immunoreactivity), astrocyte reactivity (glial fibrillary acid protein
      immunostaining), myelin (myelin basic protein immunoreactivity), ultrastructure,
      and brain derived neurotrophic factor (BDNF) levels were assessed in non-diabetic
      and diabetic animals housed in SE or EE. No differences in retinal morphology or
      retinal ganglion cell number were observed among groups. EE housing which did not
      affect the STZ-induced weight loss and hyperglycemia, prevented a decrease in the
      anterograde transport from the retina to the superior colliculus, ON axon number,
      and phosphorylated neurofilament heavy immunoreactivity. Moreover, EE housing
      prevented an increase in Iba-1 immunoreactivity, and astrocyte reactivity, as
      well as ultrastructural myelin alterations in the ON distal portion at early
      stages of diabetes. In addition, EE housing avoided a decrease in BDNF levels
      induced by experimental diabetes. These results suggest that EE induced
      neuroprotection in the diabetic visual pathway. 

PMID- 26312760
TI  - Efficient Rh-catalyzed C-H borylation of arene derivatives under photochemical
      conditions.
AB  - Photocatalysis allows innovations in organic synthesis. Among the various
      catalytic reactions, CH-functionalizations offer valuable possibilities for the
      refinement of easily available building blocks. In this respect, catalytic
      borylation is of interest, too. So far, most of the catalytic borylation
      reactions are performed under thermal conditions at comparably high temperatures.
      Here, we describe a new synthetic route for efficient borylation reactions of
      arenes using a photocatalytic pathway. This novel approach allows the synthesis
      of a broad variety of borylated arenes and heteroarenes under mild conditions.
      Applying trans-[Rh(PMe3)2(CO)Cl] as an active photocatalyst and HBPin as an boron
      source, we achieved high TON. A catalytic cycle that relies on a Rh(I)-Rh(III)
      interconversion is proposed.

PMID- 26312761
TI  - Supported gold-palladium alloy nanoparticle catalyzed tandem oxidation routes to
      N-substituted anilines from non-aromatic compounds.
AB  - In the presence of a supported gold-palladium alloy nanoparticle catalyst (Au
      Pd/Al2O3), various kinds of N-substituted anilines can be synthesized from non
      aromatic compounds. The observed catalysis is truly heterogeneous, and Au
      Pd/Al2O3 can be reused without a significant loss of its catalytic performance. 

PMID- 26312762
TI  - Sulforaphane inhibits thyroid cancer cell growth and invasiveness through the
      reactive oxygen species-dependent pathway.
AB  - Sulforaphane (SFN), a natural compound derived from broccoli/broccoli sprouts,
      has been demonstrated to be used as an antitumor agent in different types of
      cancers. However, its antitumor effect in thyroid cancer remains largely unknown.
      The aim of the study was to investigate the therapeutic potential of SFN for
      thyroid cancer and explore the mechanisms underlying antitumor effects of SFN by
      in vitro and in vivo studies. Our data demonstrated that SFN significantly
      inhibited thyroid cancer cell proliferation in a dose- and time-dependent manner,
      induced G2/M phase cell cycle arrest and apoptosis, and inhibited thyroid cancer
      cell migration and invasion by suppressing epithelial-mesenchymal transition
      (EMT) process and expression of Slug, Twist, MMP-2 and -9. Mechanically, SFN
      inhibited thyroid cancer cell growth and invasiveness through repressing
      phosphorylation of Akt, enhancing p21 expression by the activation of Erk and p38
      signaling cascades, and promoting mitochondrial-mediated apoptosis via reactive
      oxygen species (ROS)-dependent pathway. Growth of xenograft tumors derived from
      thyroid cancer cell line FTC133 in nude mice was also significantly inhibited by
      SFN. Importantly, we did not find significant effect of SFN on body weight and
      liver function of mice. Collectively, we for the first time demonstrate that SFN
      is a potentially effective antitumor agent for thyroid cancer. 

PMID- 26312763
TI  - Immunoprofile from tissue microarrays to stratify familial breast cancer
      patients.
AB  - Familial breast cancer (BC) is a heterogeneous disease with variable prognosis.
      The identification of an immunoprofile is important to predict tumor behavior for
      the routine clinical management of familial BC patients. Using
      immunohistochemistry on tissue microarrays, we studied 95 familial BCs in order
      to analyze the expression of some biomarkers involved in different pathways. We
      used unsupervised hierarchical clustering analyses (HCA), performed using the
      immunohistochemical score data, to define an immunoprofile able to characterize
      these tumors. The analyses on 95 and then on a subset of 45 tumors with all
      biomarkers contemporarily evaluable, revealed the same biomarker and patient
      clusters. Focusing on the 45 tumors we identified a group of patients
      characterized by the low expression of estrogen receptor (P = 0.009),
      progesterone receptor (P < 0.001), BRCA1 (P = 0.005), nuclear Na+/H+ exchanger
      regulatory factor 1 (NHERF1) (P = 0.026) and hypoxia inducible factor-1 alpha (P
      < 0.001), and also by the higher expression of MIB1 (P = 0.043), cytoplasmic
      NHERF1 (P = 0.004), cytoplasmic BRCT-repeat inhibitor of hTERT expression (P =
      0.001), vascular endothelial growth factor (VEGF) (P = 0.024) and VEGF receptor-1
      (P = 0.029). This immunoprofile identified a more aggressive tumor phenotype
      associated also with a larger tumor size (P = 0.012) and G3 grade (P = 0.006),
      confirmed by univariate and multivariate analyses. In conclusion, the clinical
      application of HCA of immunohistochemical data could allow the assessment of
      prognostic biomarkers to be used simultaneously. The 10 protein expression panel
      might be used to identify the more aggressive tumor phenotype in familial BC and
      to direct patients towards a different clinical therapy. 

PMID- 26312764
TI  - Estrogen related receptor alpha (ERRalpha) a promising target for the therapy of
      adrenocortical carcinoma (ACC).
AB  - The pathogenesis of the adrenocortical cancer (ACC) involves integration of
      molecular signals and the interplay of different downstream pathways (i.e.
      IGFII/IGF1R, beta-catenin, Wnt, ESR1). This tumor is characterized by limited
      therapeutic options and unsuccessful treatments. A useful strategy to develop an
      effective therapy for ACC is to identify a common downstream target of these
      multiple pathways. A good candidate could be the transcription factor estrogen
      related receptor alpha (ERRalpha) because of its ability to regulate energy
      metabolism, mitochondrial biogenesis and signalings related to cancer
      progression. In this study we tested the effect of ERRalpha inverse agonist,
      XCT790, on the proliferation of H295R adrenocortical cancer cell line. Results
      from in vitro and in vivo experiments showed that XCT790 reduced H295R cell
      growth. The inhibitory effect was associated with impaired cell cycle progression
      which was not followed by any apoptotic event. Instead, incomplete autophagy and
      cell death by a necrotic processes, as a consequence of the cell energy failure,
      induced by pharmacological reduction of ERRalpha was evidenced. Our results
      indicate that therapeutic strategies targeting key factors such as ERRalpha that
      control the activity and signaling of bioenergetics processes in high-energy
      demanding tumors could represent an innovative/alternative therapy for the
      treatment of ACC. 

PMID- 26312765
TI  - Annexin A1 is involved in the acquisition and maintenance of a stem cell
      like/aggressive phenotype in prostate cancer cells with acquired resistance to
      zoledronic acid.
AB  - In this study, we have characterized the role of annexin A1 (ANXA1) in the
      acquisition and maintenance of stem-like/aggressive features in prostate cancer
      (PCa) cells comparing zoledronic acid (ZA)-resistant DU145R80 with their parental
      DU145 cells. ANXA1 is over-expressed in DU145R80 cells and its down-regulation
      abolishes their resistance to ZA. Moreover, ANXA1 induces DU145 and DU145R80
      invasiveness acting through formyl peptide receptors (FPRs). Also, ANXA1
      knockdown is able to inhibit epithelial to mesenchymal transition (EMT) and to
      reduce focal adhesion kinase (FAK) and metalloproteases (MMP)-2/9 expression in
      PCa cells. DU145R80 show a cancer stem cell (CSC)-like signature with a high
      expression of CSC markers including CD44, CD133, NANOG, Snail, Oct4 and ALDH7A1
      and CSC-related genes as STAT3. Interestingly, ANXA1 knockdown induces these
      cells to revert from a putative prostate CSC to a more differentiated phenotype
      resembling DU145 PCa cell signature. Similar results are obtained concerning some
      drug resistance-related genes such as ATP Binding Cassette G2 (ABCG2) and Lung
      Resistant Protein (LRP). Our study provides new insights on the role of ANXA1
      protein in PCa onset and progression. 

PMID- 26312766
TI  - Rhodomycin A, a novel Src-targeted compound, can suppress lung cancer cell
      progression via modulating Src-related pathways.
AB  - Src activation is involved in cancer progression and the interplay with EGFR.
      Inhibition of Src activity also represses the signalling pathways regulated by
      EGFR. Therefore, Src has been considered a target molecule for drug development.
      This study aimed to identify the compounds that target Src to suppress lung
      cancer tumourigenesis and metastasis and investigate their underlying molecular
      mechanisms. Using a molecular docking approach and the National Cancer Institute
      (NCI) compound dataset, eight candidate compounds were selected, and we evaluated
      their efficacy. Among them, rhodomycin A was the most efficient at reducing the
      activity and expression of Src in a dose-dependent manner, which was also the
      case for Src-associated proteins, including EGFR, STAT3, and FAK. Furthermore,
      rhodomycin A significantly suppressed cancer cell proliferation, migration,
      invasion, and clonogenicity in vitro and tumour growth in vivo. In addition,
      rhodomycin A rendered gefitinib-resistant lung adenocarcinoma cells more
      sensitive to gefitinib treatment, implying a synergistic effect of the
      combination therapy. Our data also reveal that the inhibitory effect of
      rhodomycin A on lung cancer progression may act through suppressing the Src
      related multiple signalling pathways, including PI3K, JNK, Paxillin, and p130cas.
      These findings will assist the development of anti-tumour drugs to treat lung
      cancer. 

PMID- 26312768
TI  - miR408 is involved in abiotic stress responses in Arabidopsis.
AB  - MicroRNAs (miRNAs) are small RNAs that regulate the expression of target genes
      post-transcriptionally; they are known to play major roles in development and
      responses to abiotic stress. miR408 is a highly conserved miRNA in plants that
      responds to the availability of copper and targets genes encoding copper
      containing proteins. It was recently recognized to be an important component of
      the HY5-SPL7 gene network that mediates a coordinated response to light and
      copper, illustrating its central role in the response of plants to the
      environment. Expression of miR408 is significantly affected by a variety of
      developmental and ?environmental conditions; however, its biological function is
      ?unknown. Involvement of miR408 in the abiotic stress response was investigated
      in Arabidopsis. Expression of miR408, as well as its target genes, was
      investigated in response to salinity, cold, oxidative stress, drought and osmotic
      stress. Analyses of transgenic plants with modulated miR408 expression revealed
      that higher miR408 expression leads to improved tolerance to salinity, cold and
      oxidative stress, but enhanced sensitivity to drought and osmotic stress.
      Cellular antioxidant capacity was enhanced in plants with elevated miR408
      expression, as manifested by reduced levels of reactive oxygen species and
      induced expression of genes associated with antioxidative functions, including
      Cu/Zn superoxide dismutases (CSD1 and CSD2) and glutathione-S-transferase (GST
      U25), as well as auxiliary genes: the copper chaperone CCS1 and the redox stress
      associated gene SAP12. Overall, the results demonstrate significant involvement
      of miR408 in abiotic stress responses, emphasizing the central function of miR408
      in plant survival. 

PMID- 26312767
TI  - Metastatic Low-Grade Gliomas in Children: 20 Years' Experience at St. Jude
      Children's Research Hospital.
AB  - BACKGROUND: Patients with low-grade gliomas (LGG), which are the most common
      childhood brain tumors, have excellent long-term survival. Dissemination of LGG
      is rare. Robust data on the incidence, presentation, patterns of dissemination,
      disease behavior, outcome, and best-management approaches do not exist. We
      describe 20 years of follow-up of children with metastatic LGG. PROCEDURE: Data
      collected during the period 1990-2010 were retrospectively reviewed for the
      following inclusion criteria: diagnosis of metastatic LGG, age younger than 21
      years at initial diagnosis, and magnetic resonance imaging of the brain and/or
      spine at diagnosis and/or follow-up. Patient demographics, pathology, treatment
      modalities, and outcome were reviewed. RESULTS: Of 599 patients with LGG, 38 (6%)
      had metastatic disease at either diagnosis or follow-up. Most tumors (87%) were
      located in the brain, and half of the patients had metastatic disease at
      presentation. The most common diagnosis was pilocytic astrocytoma (55%).
      Chemotherapy was the most common initial treatment modality. Median survival of
      the group was 6.2 years (range, 0.1-16.9 years). Fifteen (40%) patients died at a
      median of 6 years from diagnosis (range, 0.8-15 years). Overall survival at 5,
      10, and 15 years was 80.7 +/- 6.6%, 63.0 +/- 10.2%, and 50.9 +/- 16.0%,
      respectively. CONCLUSION: This study describes the longest follow-up of children
      with metastatic LGG. LGG is underestimated and entails major morbidity and
      mortality. Prospective studies are needed to learn the true incidence, study the
      biology, and determine the best approaches to diagnosis, treatment, and follow
      up.

PMID- 26312770
TI  - HMGB1 Turns Renal Tubular Epithelial Cells into Inflammatory Promoters by
      Interacting with TLR4 During Sepsis.
AB  - Our study was undertaken to investigate whether the inflammatory mediator high
      mobility group box 1 (HMGB1) can enter the renal tissue and urine and what is the
      functional change of renal tubular epithelial cells (TECs) interacting with HMGB1
      during sepsis. We found that the transcription levels of interleukin 1 (IL-1) and
      interleukin 6 (IL-6) mRNA in TECs increased significantly during sepsis and these
      processes can be blocked by splenectomy. We also found out HMGB1 accumulated in
      the renal tissue and entered urine during sepsis and toll-like receptor 4 (TLR4)
      was expressed by TECs. In vitro, we demonstrated that HMGB1 induced MAPK and NF
      kappaB activation and G1 cell cycle arrest in TECs. We also found that the mRNA
      transcription levels of IL-1, IL-6, and tissue inhibitor of metalloproteinases 2
      (TIMP2) increased significantly and the IL-1, IL-6, and TIMP2 can be secreted by
      TECs stimulated by HMGB1. In contrast, LPS RS can block all of the processes
      above in vitro. In vivo, the increase of the mRNA transcription level of TIMP2
      was also observed. These data indicate that HMGB1 accumulates in renal tissue and
      enters the urine and the interaction between HMGB1 and TLR4 turns TECs into
      inflammatory promoters during sepsis. 

PMID- 26312771
TI  - Industrial processing of condiments and seasonings and its implications for
      micronutrient fortification.
AB  - Opportunities exist for micronutrient fortification of condiments and seasonings
      to combat vitamin or mineral deficiencies. This paper reviews the available
      technologies for industrial processing of condiments and seasonings and their
      fortification with micronutrients. The industrial processes to manufacture
      commonly consumed condiments and seasonings, such as soy sauce, bouillon cubes,
      fish sauce, spices, and other relevant products, are described. The impact of
      processing on fortification is evaluated, considering both the type of vehicle
      and the fortificant used. The analyzed technologies represent effective
      strategies for mineral fortification, particularly with iodine and iron. However,
      fortification with vitamins has been more challenging, owing to sensory changes
      of the finished product and a poor stability of the fortificant when using
      certain vehicles. Therefore, more studies are needed in this area in
      collaboration with governments, the food industry, and vitamin suppliers. Despite
      the technical difficulties encountered, the current processing technologies for
      the production of condiments and seasonings can be adapted and refined to allow
      their successful fortification with micronutrients. 

PMID- 26312772
TI  - A Model of Consumer Response to Over-the-Counter Drug Advertising: Antecedents
      and Influencing Factors.
AB  - Given the importance of over-the-counter (OTC) drugs in the health care
      marketplace and lack of systematic research on OTC drug advertising (OTCA)
      effects, this study tested a theory-based, product category-specific OTCA effects
      model. Structural equation modeling analysis of data for 1 OTC drug category,
      analgesics, supported the proposed model, explaining the OTCA effect process from
      key consumer antecedents to ad involvement, from ad involvement to ad attention,
      from ad attention to cognitive responses, then to affective/evaluative responses,
      leading to the final behavioral outcome. Several noteworthy patterns also
      emerged: (a) Product involvement was directly linked to ad attention, rather than
      exerting an indirect influence through ad involvement; (b) ad attention was
      significantly related to both cognitive and affective/evaluative responses to
      different degrees, with stronger links to cognitive responses; and 

PMID- 26312773
TI  - Effect of resveratrol on experimental non-alcoholic fatty liver disease depends
      on severity of pathology and timing of treatment.
AB  - BACKGROUND AND AIM: Non-alcoholic steatohepatitis (NASH) is a leading cause of
      chronic liver disease with few therapeutic options. Resveratrol (RSV) prevents
      the development of steatosis in a number of experimental fatty liver (non
      alcoholic fatty liver [NAFL]) models, but the preventive or therapeutic effects
      on experimental NASH are not yet clarified, and clinical results on non-alcoholic
      fatty liver disease are ambiguous. Thus, we aimed to compare the RSV-mediated
      preventive and therapeutic effects on experimental NAFL and NASH. METHODS: We
      used a high-fat (HF) diet to generate a rat NAFL model and a high-fat, high
      cholesterol (HFC) diet to generate a rat NASH model. The preventive and
      therapeutic potential of RSV was tested by adding RSV to the HF and HFC diet from
      study start or after 1 week of the diets. Animals were sacrificed after 8 weeks
      with appropriate controls. Blood and liver were harvested for analysis, including
      measurement of RSV metabolites. RESULTS: Resveratrol reduced the development of
      histological steatosis (P = 0.03) and partly triglyceride accumulation (fold
      change reduced from 3.6 to 2.4, P = 0.08) in the male NAFL model, although
      effects were moderate. In NASH prevention, RSV reduced the accumulation of
      triglyceride in hepatic tissue (P < 0.01), while there was no effect on
      biochemical, histopathological, or transcriptional NASH changes. Further, RSV had
      no therapeutic effect on established NASH. We found RSV metabolites but no parent
      RSV in serum or liver tissue, confirming low bioavailability. CONCLUSIONS: These
      experimental findings suggest that a weak hepatic benefit of RSV treatment is
      seen in prevention of steatosis only.

PMID- 26312774
TI  - Noncanonical Stacking Geometries of Nucleobases as a Preferred Target for Solar
      Radiation.
AB  - Direct DNA absorption of UVB photons in a spectral range of 290-320 nm of
      terrestrial solar radiation is responsible for formation of cyclobutane
      pyrimidine dimers causing skin cancer. Formation of UVB-induced lesions is not
      random, and conformational features of their hot spots remain poorly understood.
      We calculated the electronic excitation spectra of thymine, cytosine, and adenine
      stacked dimers with ab initio methods in a wide range of conformations derived
      from PDB database and molecular dynamics trajectory of thymine-containing
      oligomer. The stacked dimers with reduced interbase distances in curved, hairpin
      like, and highly distorted DNA and RNA structures exhibit excitonic transitions
      red-shifted up to 0.6 eV compared to the B-form of stacked bases, which makes
      them the preferred target for terrestrial solar radiation. These results might
      have important implications for predicting the hot spots of UVB-induced lesions
      in nucleic acids. 

PMID- 26312775
TI  - Should the General Medical Council explore the use of digital badges?

PMID- 26312776
TI  - The Role of Shape and Heart Rate on the Performance of the Left Ventricle.
AB  - The left ventricle function is to pump the oxygenated blood through the
      circulatory system. Ejection fraction is the main noninvasive parameter for
      detecting heart disease (healthy >55%), and it is thought to be the main
      parameter affecting efficiency. However, the effects of other parameters on
      efficiency have yet to be investigated. We investigate the effect of heart rate
      and left ventricle shape by carrying out 3D numerical simulations of a left
      ventricle at different heart rates and perturbed geometries under constant,
      normal ejection fraction. The simulation using the immersed boundary method
      provide the 3D flow and pressure fields, which enable direct calculation of a new
      hemodynamic efficiency (H-efficiency) parameter, which does not depend on any
      reference pressure. The H-efficiency is defined as the ratio of flux of kinetic
      energy (useful power) to the total cardiac power into the left ventricle control
      volume. Our simulations show that H-efficiency is not that sensitive to heart
      rate but is maximized at around normal heart rate (72 bpm). Nevertheless, it is
      more sensitive to the shape of the left ventricle, which affects the H-efficiency
      by as much as 15% under constant ejection fraction.

PMID- 26312777
TI  - Treatment Effect and Corneal Light Scattering With 2 Corneal Cross-linking
      Protocols: A Randomized Clinical Trial.
AB  - IMPORTANCE: We describe and evaluate a complementary method to indirectly
      quantify the treatment effect of corneal cross-linking (CXL). Additional methods
      to indirectly quantify the treatment effect of CXL are needed. OBJECTIVE: To
      assess the spatial distribution and the time course of the increased corneal
      densitometry (corneal light backscatter) seen after CXL with riboflavin and UV-A
      irradiation. DESIGN, SETTING, AND PARTICIPANTS: Open-label randomized clinical
      trial of 43 patients (60 eyes) who were 18 to 28 years of age and had progressive
      keratoconus and a plan to be treated with CXL at Umea University Hospital, Umea,
      Sweden. The patients were randomized to receive conventional CXL (n = 30) using
      the Dresden protocol or CXL with mechanical compression of the cornea using a
      flat rigid contact lens sutured to the cornea during the treatment (CRXL) (n =
      30). All participants were followed up during a 6-month period from October 13,
      2009, through May 31, 2012. INTERVENTIONS: Corneal cross-linking according to the
      Dresden protocol or CRXL. MAIN OUTCOMES AND MEASURES: Change in corneal
      densitometry after CXL and CRXL for keratoconus. RESULTS: Of the original 60 eyes
      included, 4 had incomplete data. A densitometry increase was seen after both
      treatments that was deeper and more pronounced in the CXL group (difference
      between the groups at 1 month in the center layer, zone 0-2 mm, 5.02 grayscale
      units [GSU], 95% CI, 2.92-7.12 GSU; P < .001). This increase diminished with time
      but was still noticeable at 6 months (difference between the groups at 6 months
      in the center layer, zone 0-2 mm, 3.47 GSU; 95% CI, 1.72-5.23 GSU; P < .001) and
      was proportional to the reduction in corneal steepness (R = -0.45 and -0.56 for
      CXL and CRXL, respectively). CONCLUSIONS AND RELEVANCE: The degree of corneal
      light backscatter relates to the reduction in corneal steepness after cross
      linking and may become a relevant complement to other methods in evaluating the
      cross-linking effect, for example, when comparing different treatment regimens.
      TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02425150.

PMID- 26312778
TI  - Gaining insight into the catalysis by GH20 lacto-N-biosidase using small molecule
      inhibitors and structural analysis.
AB  - The synthesis of potent inhibitors for lacto-N-biosidases and X-ray structural
      characterization of these compounds in complex with BbLNBase is described. 

PMID- 26312779
TI  - Microarray analysis of pancreatic gene expression during biotin repletion in
      biotin-deficient rats.
AB  - Biotin is a B vitamin involved in multiple metabolic pathways. In humans, biotin
      deficiency is relatively rare but can cause dermatitis, alopecia, and perosis.
      Low biotin levels occur in individuals with type-2 diabetes, and supplementation
      with biotin plus chromium may improve blood sugar control. The acute effect on
      pancreatic gene expression of biotin repletion following chronic deficiency is
      unclear, therefore we induced biotin deficiency in adult male rats by feeding
      them a 20% raw egg white diet for 6 weeks. Animals were then randomized into 2
      groups: one group received a single biotin supplement and returned to normal chow
      lacking egg white, while the second group remained on the depletion diet. After 1
      week, pancreata were removed from biotin-deficient (BD) and biotin-repleted (BR)
      animals and RNA was isolated for microarray analysis. Biotin depletion altered
      gene expression in a manner indicative of inflammation, fibrosis, and defective
      pancreatic function. Conversely, biotin repletion activated numerous repair and
      anti-inflammatory pathways, reduced fibrotic gene expression, and induced
      multiple genes involved in pancreatic endocrine and exocrine function. A subset
      of the results was confirmed by quantitative real-time PCR analysis, as well as
      by treatment of pancreatic AR42J cells with biotin. The results indicate that
      biotin repletion, even after lengthy deficiency, results in the rapid induction
      of repair processes in the pancreas. 

PMID- 26312780
TI  - Micellar electrokinetic chromatography with short-end injection for rapid
      separation and simultaneous determination of aesculin, aesculetin, and
      phenylephrine in pharmaceutical preparations.
AB  - A fast micellar electrokinetic chromatography (MEKC) method for simultaneous
      assay of aesculin, aesculetin, and phenylephrine was developed and validated. The
      separation was carried out in a fused-silica capillary (50 MUm id, total length
      64.5 cm, effective length 8.5 cm) with UV detection at 210 nm, temperature 25
      degrees C and separation voltage -25 kV. The samples were loaded hydrodynamically
      at a pressure of -50 mbar for 6 s. The background electrolyte of pH 8.6 contained
      20 mM boric acid, 60 mM SDS, and 5% (v/v) of methanol. The calibration curves
      were linear in the range 10-500 MUg/mL for aesculin and aesculetin and 12.5-625
      MUg/mL for phenylephrine. The RSD values of corrected peak areas were 0.6-1.2% (n
      = 6) when determining 0.2 mg/mL of aesculin and aesculetin and 0.25 mg/mL of
      phenylephrine in prepared standard mixtures. The method was successfully applied
      to the assay of aesculin and phenylephrine in a pharmaceutical preparation (RSD 
      =  1.9-2.0%; n  =  3) and the robustness of the method for both, the
      determination of analytes and the system suitability test parameter values, was
      evaluated with the use of Plackett-Burman design.

PMID- 26312781
TI  - Converting Skin Fibroblasts into Hepatic-like Cells by Transient Programming.
AB  - Transplantation of hepatocytes is a promising therapy for end-stage liver
      disease, but the availability of functional cells currently precludes its
      clinical application. We now report a simple transient reprogramming approach to
      convert fibroblasts into hepatic-like cells. Human skin fibroblasts were treated
      with fish egg extracts to become the transiently remodeled cells (TRCs). After
      infected with retroviral EGFP, they were directly injected into the fetal monkey
      liver, where they underwent in situ differentiation in the hepatic niche. The
      hepatic-like cells were functional as shown by the synthesis of hepatic markers
      in vivo, including albumin, cytokeratin-18, and hepatic serum antigen. Similarly,
      when implanted in the mouse liver, the TRCs were differentiated into hepatic-like
      cells that synthesize albumin and CK18 and became completely integrated into the
      liver parenchyma. The potency of TRCs was mechanistically related to the
      activation of several signal pathways, which reactivate endogenous genes related
      to cell potency. This study demonstrates the feasibility of a simple and
      inexpensive epigenetic remodeling approach to convert human fibroblasts into
      therapeutic hepatic-like cells for the treatment of end-stage liver disease.

PMID- 26312782
TI  - Localization-guided surgery for breast cancer.

PMID- 26312783
TI  - Origin of Sub-Bandgap Electroluminescence in Organic Light-Emitting Diodes.
AB  - Sub-bandgap electroluminescence in organic light emitting diodes is a phenomenon
      in which the electroluminescence turn-on voltage is lower than the bandgap
      voltage of the emitter. Based on the results of transient electroluminescence
      (EL) and photoluminescence and electroabsorption spectroscopy measurements, it is
      concluded that in rubrene/C60 devices, charge transfer excitons are generated at
      the rubrene/C60 interface under sub-bandgap driving conditions, leading to the
      formation of triplet excitons, and sub-bandgap EL is the result of the subsequent
      triplet-triplet annihilation process. 

PMID- 26312784
TI  - Race, Health, and Politics.

PMID- 26312785
TI  - Letting Patients and Families Interpret Deathbed Phenomena for Themselves.
AB  - Nurses and other clinicians shouldn't explain away these often meaningful
      experiences. 

PMID- 26312786
TI  - Willful Blindness.

PMID- 26312787
TI  - Willful Blindness.

PMID- 26312788
TI  - Accelerated Nursing Programs.

PMID- 26312789
TI  - OSHA Gets Serious About Workplace Safety for Nurses.
AB  - New guidance on inspections in health care settings. 

PMID- 26312790
TI  - Food Companies Have Three Years to Eliminate Trans Fats.
AB  - A product intended to extend shelf life has been found to cause myriad health
      problems. 

PMID- 26312793
TI  - Kids and Marijuana Edibles: A Worrisome Trend Emerges.
AB  - Experts say states should mandate child-resistant packaging. 

PMID- 26312794
TI  - Work on Safe Staffing Guidelines Halted in the United Kingdom.
AB  - Establishing safe nurse staffing levels is no easier abroad than in the United
      States. 

PMID- 26312798
TI  - The Case for License Portability.
AB  - All RNs sit for the same exam, so why not agree on licensure requirements? 

PMID- 26312799
TI  - Nurses Come Together in Seoul to Discuss Common Issues and Challenges.

PMID- 26312806
TI  - Improving Pediatric Temperature Measurement in the ED.
AB  - OVERVIEW: ED care providers have long debated which of the various methods of
      temperature measurement of pediatric patients is best. While the efficacy and
      accuracy of temporal artery, tympanic membrane, axillary, and infrared
      temperature measurement have been studied, the gold standard has been rectal
      temperature measurement. But despite its accuracy, this method causes children
      with noninfectious complaints and their families unnecessary distress and adds
      significant time to the triage process. In response, a group of ED staff nurses
      at a multihospital health system conducted an evidence-based quality improvement
      project to determine the best practice for accurate temperature measurement in
      children younger than five years who presented to the ED. The project included an
      exhaustive literature search, a review of relevant studies, the development of a
      table of evidence, a presentation of the findings, and recommendations for
      practice change. This article describes the project and the adoption of temporal
      artery thermometry, a painless, noninvasive screening method that provided
      consistently accurate temperature measurement as well as increased patient and
      nurse satisfaction and a shorter triage process.

PMID- 26312807
TI  - Life in Amman.
AB  - Editor's note: This column chronicles the author's experience teaching abroad
      this past year. 

PMID- 26312808
TI  - Conflict Engagement: Creating Connection and Cultivating Curiosity.
AB  - This article is one in a series on conflict. It is part of an ongoing series on
      leadership coordinated by the American Organization of Nurse Executives (AONE;
      www.aone.org), highlighting topics of interest to nurse managers and emerging
      nurse leaders. The AONE provides leadership, professional development, advocacy,
      and research to advance nursing practice and patient care, promote nursing
      leadership excellence, and shape public policy for health care. 

PMID- 26312809
TI  - Teaching Crucial Knowledge vs. Helping Out on the Unit.
AB  - When a clinical instructor must weigh the duty to educate against urgent patient
      care needs. 

PMID- 26312814
TI  - Coming Home to Nursing.
AB  - A new profession provides an unexpected sense of belonging. 

PMID- 26312815
TI  - Effective capture of circulating tumor cells from a transgenic mouse lung cancer
      model using dendrimer surfaces immobilized with anti-EGFR.
AB  - The lack of an effective detection method for lung circulating tumor cells (CTCs)
      presents a substantial challenge to elucidate the value of CTCs as a diagnostic
      or prognostic indicator in lung cancer, particularly in nonsmall cell lung cancer
      (NSCLC). In this study, we prepared a capture surface exploiting strong
      multivalent binding mediated by poly(amidoamine) (PAMAM) dendrimers to capture
      CTCs originating from lung cancers. Given that 85% of the tumor cells from NSCLC
      patients overexpress epidermal growth factor receptor (EGFR), anti-EGFR was
      chosen as a capture agent. Following in vitro confirmation using the murine lung
      cancer cell lines (ED-1 and ED1-SC), cyclin E-overexpressing (CEO) transgenic
      mice were employed as an in vivo lung tumor model to assess specificity and
      sensitivity of the capture surface. The numbers of CTCs in blood from the CEO
      transgenic mice were significantly higher than those from the healthy controls
      (on average 75.3 +/- 14.9 vs 4.4 +/- 1.2 CTCs/100 MUL of blood, p < 0.005),
      indicating the high sensitivity and specificity of our surface. Furthermore, we
      found that the capture surface also offers a simple, effective method for
      monitoring treatment responses, as observed by the significant decrease in the
      CTC numbers from the CEO mice upon a treatment using a novel anti-miR-31 locked
      nucleic acid (LNA), compared to a vehicle treatment and a control-LNA treatment
      (p < 0.05). This in vivo evaluation study confirms that our capture surface is
      highly efficient in detecting in vivo CTCs and thus has translational potential
      as a diagnostic and prognostic tool for lung cancer. 

PMID- 26312820
TI  - Assessing Nursing Students' Knowledge of Genomic Concepts and Readiness for Use
      in Practice.
AB  - Nurses are expected to apply genomic concepts in clinical practice. This study
      evaluated undergraduate nursing students' genomic knowledge and attitudes about
      using this knowledge in practice. Using a pretest-posttest design, findings
      indicated that students' knowledge was poor, but improved over a semester with
      genomics content. Most students did not feel ready to use this knowledge in the
      clinical setting. These findings suggest the need for more genomic education in
      nursing curriculum.

PMID- 26312821
TI  - Honors Programs: Current Perspectives for Implementation.
AB  - The changing demographics of the nursing workforce, including large numbers of
      impending retirements, highlight the need for innovative programs to attract the
      next generation of nursing leaders, educators, and researchers. Nursing honors
      programs provide an enhanced educational experience for high-achieving and highly
      motivated students, developing them as future nursing leaders. This review
      describes the current perspectives, characteristics, and values of nursing honors
      programs, opportunities for implementation, and recommendations for integration
      within nursing education.

PMID- 26312822
TI  - Is Cognitive Test-Taking Anxiety Associated With Academic Performance Among
      Nursing Students?
AB  - The cognitive component of test anxiety was correlated with academic performance
      among nursing students. Modest but statistically significant lower examination
      grade T scores were observed for students with high compared with low levels of
      cognitive test anxiety (CTA). High levels of CTA were associated with reduced
      academic performance.

PMID- 26312823
TI  - Business Continuity Planning for Nursing Schools: Preparation for Potential
      Disasters.
AB  - Nursing schools are vulnerable to disasters, ranging from pandemics to weather
      emergencies, fires, and acts of terrorism. To ensure minimal disruptions to
      teaching, provision of care, research, and other critical missions, nursing
      faculty and administrative leaders should develop a business continuity plan. The
      business continuity plan can help faculty, students, and administration identify
      critical functions and alternative plans if an emergency occurs. We offer our
      experience as a guide for other nursing schools.

PMID- 26312824
TI  - Learning Teams and the Online Learner.

PMID- 26312825
TI  - AMPK/p53 Axis Is Essential for alpha-Lipoic Acid-Regulated Metastasis in Human
      and Mouse Colon Cancer Cells.
AB  - alpha-Lipoic acid (ALA) has an anticancer property of lung, cervix, and prostate
      cancer cells. However, direct evidence that ALA contributes to the development of
      colon cancer has not been fully elucidated. In addition, no previous studies have
      evaluated whether ALA may regulate malignant potential, such as adhesion,
      invasion, and colony formation of colon cancer cells. To address the
      aforementioned questions, we conducted in vitro ALA signaling studies using human
      (HT29) and mouse (MCA38) colon cancer cell lines. We observed that cell
      proliferation is reduced by ALA administration in a dose-dependent manner in
      human and mouse colon cancer cell lines. Specifically, 0.5 to 1 mM concentration
      of ALA significantly decreased cell proliferation when compared with control.
      Similarly, we found that ALA downregulates adhesion, invasion, and colony
      formation. Finally, we observed that ALA activates p53 and AMPK signaling
      pathways in human and mouse colon cancer cells. We found for the first time that
      ALA suppresses cell proliferation and malignant potential via p53 and AMPK
      signaling pathways in human and mouse colon cancer cells. These new and early
      mechanistic studies provide a causal role of ALA in colon cancer, suggesting that
      ALA might be a useful agent in the management or chemoprevention of colon cancer.

PMID- 26312826
TI  - A germline chromothripsis event stably segregating in 11 individuals through
      three generations.
AB  - PURPOSE: Parentally transmitted germ-line chromothripsis (G-CTH) has been
      identified in only a few cases. Most of these rearrangements were stably
      transmitted, in an unbalanced form, from a healthy mother to her child with
      congenital abnormalities probably caused by de novo copy-number changes of dosage
      sensitive genes. We describe a G-CTH transmitted through three generations in 11
      healthy carriers. METHODS: Conventional cytogenetic analysis, mate-pair
      sequencing, and polymerase chain reaction (PCR) were used to identify the
      chromosome rearrangement and characterize the breakpoints in all three
      generations. RESULTS: We identified an apparently balanced translocation t(3;5),
      later shown to be a G-CTH, in all individuals of a three-generation family. The G
      CTH stably segregated without occurrence of additional rearrangements; however,
      several spontaneous abortions were reported, possibly due to unbalanced
      transmission. Although seven protein-coding genes are interrupted, no clinical
      features can be definitively attributed to the affected genes. However, it can be
      speculated that truncation of one of these genes, encoding ataxia-telangiectasia
      and Rad3-related protein kinase (ATR), a key component of the DNA damage
      response, may be related to G-CTH formation. CONCLUSION: G-CTH rearrangements are
      not always associated with abnormal phenotypes and may be misinterpreted as
      balanced two-way translocations, suggesting that G-CTH is an underdiagnosed
      phenomenon.Genet Med 18 5, 494-500.

PMID- 26312827
TI  - Rapid progression and mortality of lysosomal acid lipase deficiency presenting in
      infants.
AB  - PURPOSE: The purpose of this study was to enhance understanding of lysosomal acid
      lipase deficiency (LALD) in infancy. METHODS: Investigators reviewed medical
      records of infants with LALD and summarized data for the overall population and
      for patients with and without early growth failure (GF). Kaplan-Meier survival
      analyses were conducted for the overall population and for treated and untreated
      patients. RESULTS: Records for 35 patients, 26 with early GF, were analyzed.
      Prominent symptom manifestations included vomiting, diarrhea, and steatorrhea.
      Median age at death was 3.7 months; estimated probability of survival past age 12
      months was 0.114 (95% confidence interval (CI): 0.009-0.220). Among patients with
      early GF, median age at death was 3.5 months; estimated probability of survival
      past age 12 months was 0.038 (95% CI: 0.000-0.112). Treated patients
      (hematopoietic stem cell transplant (HSCT), n = 9; HSCT and liver transplant, n =
      1) in the overall population and the early GF subset survived longer than
      untreated patients, but survival was still poor (median age at death, 8.6
      months). CONCLUSIONS: These data confirm and expand earlier insights on the
      progression and course of LALD presenting in infancy. Despite variations in the
      nature, onset, and severity of clinical manifestations, and treatment attempts,
      clinical outcome was poor.Genet Med 18 5, 452-458.

PMID- 26312829
TI  - Phosphate as a cardiovascular risk factor: effects on vascular and endothelial
      function.
AB  - BACKGROUND: Hyperphosphataemia is a risk factor for accelerated cardiovascular
      disease in chronic kidney disease. The mechanism is poorly understood; it is
      unclear whether phosphate has direct effects or effects mediated via
      calcification or FGF23. We investigated direct effects of phosphate on
      endothelial function using myography to study rat and human blood vessels. In
      addition we assessed the effects of phosphate loading on endothelial function in
      a clinical study. METHODS: Resistance vessels from patients with (n=12) and
      without (n=13) chronic kidney disease were incubated in normal or high phosphate.
      Vasoconstrictor and vasorelaxation responses were measured. Concentration
      response curves were constructed and comparisons made. Identical experiments were
      performed in rat mesenteric vessels with and without phosphodiesterase type 5
      inhibitor. A cross-over study was done in 19 healthy volunteers receiving
      phosphate supplements or binders and endothelial function measured by flow
      mediated dilatation (FMD). Primary outcome was percent change in FMD from
      baseline. FINDINGS: Nine to 13 vessels were used in each group. Endothelium
      dependent vasodilatation was impaired in high compared with normal phosphate in
      rat (mean maximum vasodilatation 64% [SE 9] vs 95 [1], p<0.001) and human vessels
      with (25.3 [11.1] vs 75.7 [13.6], p<0.001) and without chronic kidney disease
      (42.9 [12] vs 79.4 [8.2], p=0.003). In rat vessels, these effects were reversed
      by a phosphodiesterase type 5 inhibitor. In vivo in volunteers, endothelial
      function was reduced by phosphate loading (median maximum vasodilatation 3.38%
      [IQR 2.57-5.26] vs 8.4 [6.2-11.6], p<0.001); this effect was independent of serum
      phosphate concentration but associated with urinary phosphate excretion and serum
      FGF23 concentrations. INTERPRETATION: Prolonged exposure to phosphate is
      associated with endothelial dysfunction, a direct effect of phosphate, which
      might contribute to cardiovascular risk in chronic kidney disease. In a high
      phosphate environment, endothelial and vascular dysfunction is evident in blood
      vessels and in man exposed to prolonged oral phosphate loading. These effects
      might be mediated by disruption of the NO pathway. FUNDING: British Heart
      Foundation, Darlinda's Charity for Renal Research.

PMID- 26312830
TI  - Circulating plasma microRNAs as a screening method for detection of colorectal
      adenomas.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNA molecules. Reduced or
      increased levels of specific miRNAs are observed in colon and other cancers,
      supporting their role in carcinogenesis. Detection of colorectal polyps is the
      cornerstone of the Bowel Cancer Screening Programme in the UK. However, uptake of
      screening nationally remains under 60%. We aimed to see whether circulating
      plasma miRNAs can be used to screen for patients with colorectal polyps,
      adenomas, or both. METHODS: Blood samples were taken from patients from the Bowel
      Cancer Screening Programme (asymptomatic but faecal occult blood testing [FOBt]
      positive). Plasma RNA was extracted, target miRNAs (19a, 98, 146b, 186, 191,
      222*, 331-5p, 452, 625, 664, 1247) were identified on pooled case miRNA assay
      cards, and miRNA fraction was quantified by quantitative RT-PCR assay. Results
      were compared with endoscopy reports and with histology of any polyps identified
      and removed. Analysis was done with Excel (2011) and SPSS (version 20) software.
      FINDINGS: 210 patients were included (117 with polyps, 12 with cancer, 81 healthy
      controls [FOBt positive]). The miRNA panel showed significant differences in
      expression (on t testing) for patients compared with controls for those with
      polyps, cancer, or both (miR-19a, p=0.0184; miR-98, p=0.0206; miR-146b, p=0.0029;
      miR-186, p=0.0006; miR-62,5 p=0.0008), polyps (miR-19a, p=0.0233; miR-98,
      p=0.0224; miR-146b, p=0.003; miR-186, p=0.0004; miR-625, p=0.001), adenomas (miR
      19a, p=0.0339; miR-98, p=0.0266; miR-146b, p=0.0045; miR-186, p=0.0008; miR-625,
      p=0.0049), multiple adenomas (both sides of colon; miR-146b, p=0.0194; miR-186,
      p=0.0226; miR-625, p=0.0013), and right-sided adenomas (miR-98, p=0.031; miR
      146b, p=0.0076; miR-186, p=0.0041; miR-331-5p, p=0.0142; miR-625, p=0.0049).
      Receiver operating characteristic analysis showed sensitivity of 60% or more, and
      specificity of 86% or more for men with polyps, men with adenomas, all patients
      with haemorrhoids or diverticulosis and polyps, and all patients with
      haemorrhoids or diverticulosis and adenomas. INTERPRETATION: The target miRNAs
      that we identified showed significant differences in expression levels for
      patients with polyps and patients with adenomas from controls. Use of this panel
      has potential as a screening test. FUNDING: Bowel Disease Research Foundation.

PMID- 26312828
TI  - The genetic landscape of Alzheimer disease: clinical implications and
      perspectives.
AB  - The search for the genetic factors contributing to Alzheimer disease (AD) has
      evolved tremendously throughout the years. It started from the discovery of fully
      penetrant mutations in Amyloid precursor protein, Presenilin 1, and Presenilin 2
      as a cause of autosomal dominant AD, the identification of the E4 allele of
      Apolipoprotein E as a strong genetic risk factor for both early-onset and late
      onset AD, and evolved to the more recent detection of at least 21 additional
      genetic risk loci for the genetically complex form of AD emerging from genome
      wide association studies and massive parallel resequencing efforts. These
      advances in AD genetics are positioned in light of the current endeavor directing
      toward translational research and personalized treatment of AD. We discuss the
      current state of the art of AD genetics and address the implications and
      relevance of AD genetics in clinical diagnosis and risk prediction,
      distinguishing between monogenic and multifactorial AD. Furthermore, the
      potential and current limitations of molecular reclassification of AD to
      streamline clinical trials in drug development and biomarker studies are
      addressed.Genet Med 18 5, 421-430.

PMID- 26312831
TI  - Tumour metabolism in squamous cell carcinoma of the head and neck: an in-vitro
      study of the consequences of TP53 mutation and therapeutic implications.
AB  - BACKGROUND: Survival for squamous cell carcinoma of the head and neck (SCCHN) has
      not improved substantially in recent years. Since radiotherapy is a cornerstone
      of treatment, it is crucial to identify ways to augment its efficacy, for which
      tumour metabolism is an attractive target. p53 is a metabolic mediator, and TP53
      mutations are common in this disorder. We sought to investigate metabolic changes
      in SCCHN, to elucidate any correlation with TP53 status, and to determine whether
      targeted metabolic therapy might be used to potentiate the effects of radiation.
      METHODS: Extracellular acidification and oxygen consumptions rates, respective
      measures of glycolytic flux and mitochondrial respiration, were assayed in real
      time for a panel of wild-type (wt) and mutant (mut) TP53 SCCHN cell lines in an
      extracellular flux analyser (XF24, Seahorse Bioscience, Billerica, MA, USA)
      during specifically designed stress tests. Sensitivity to radiation with or
      without 25mM 2-deoxyglucose (glycolytic inhibitor) was evaluated in clonogenic
      assays. FINDINGS: MutTP53 SCCHN cell lines showed a distinct metabolic phenotype
      from that of wtTP53 cells: wtTP53 cells maintained metabolic diversity,
      displaying robust mitochondrial and glycolytic reserve capacities, whereas
      mutTP53 cells displayed glycolytic dependence with markedly reduced mitochondrial
      and glycolytic reserve, functioning near capacity under basal conditions. This
      metabolic shift, in turn, correlated with radiation response after administration
      of 2-deoxyglucose, which significantly (p<0.05) potentiated effects of radiation
      in mutTP53 but not wtTP53 cells. INTERPRETATION: TP53 mutation in SCCHN seems to
      correlate with a metabolic shift away from mitochondrial respiration towards
      glycolysis, resulting in sensitivity to the potentiating effects of glycolytic
      inhibition on radiation. Consequently, TP53 status could be applied clinically as
      a marker of metabolic phenotype in SCCHN, enabling a more tailored therapeutic
      approach, which would also specifically target the typically treatment-resistant
      disease associated with TP53 mutation. FUNDING: Cancer Research UK, Royal College
      of Surgeons of England.

PMID- 26312832
TI  - Microvascular and endothelial function for risk prediction in dengue: an
      observational study.
AB  - BACKGROUND: Dengue infection can result in a wide spectrum of disease. The
      defining feature of severe disease is increased capillary permeability, which can
      lead to hypovolaemic shock. Microvascular and endothelial dysfunction might
      underlie hypovolaemic shock, but they have not been assessed clinically. We aimed
      to investigate the use of microvascular assessment as a prognostic method in
      dengue. METHODS: This is an ongoing prospective observational study that aims to
      recruit 300 participants: children over the age of 3 years and adults presenting
      to two outpatient departments in Vietnam with fever of less than 72 h duration
      and suspected dengue, and patients admitted to hospital with warning signs or
      severe disease. Participants are being clinically assessed daily for 6 days, and
      2 weeks later. Microvascular imaging using sublingual sidestream darkfield
      imaging (SDF) and endothelial function testing using peripheral artery tonometry
      are being performed at enrolment, defervescence, and follow-up FINDINGS: To date,
      167 patients have been recruited (92 outpatient arm, 75 inpatient arm, median age
      27 years [IQR 21-33], 78 male [47%]). Dengue has been confirmed in 67 individuals
      in the outpatient arm, of whom 29 (43%) developed warning signs, three (4%)
      developed severe disease, and 35 had uncomplicated dengue; the other 25
      outpatients (27%) were diagnosed as other febrile illness. At enrolment, the
      reactive hyperaemic index, a marker of endothelial function, was lowest in the
      patients who went on to develop severe dengue (median 1.54, IQR 1.36-1.77)
      followed by those who developed warning signs (1.78, 1.43-2.36) and then
      uncomplicated dengue (2.18, 1.65-2.24). Initial SDF results showed a lower
      proportion of perfused vessels and mean flow index during the febrile phase of
      dengue compared with follow-up, and were worst in the severe group at
      defervescence. INTERPRETATION: This study of vascular function at serial
      timepoints in dengue is, to our knowledge, the first and most comprehensive. Our
      preliminary results suggest that microvascular and endothelial dysfunction are
      associated with severity of dengue, and occur before the appearance of severe
      clinical manifestations. These techniques might be useful in risk prediction in
      dengue. A limitation is that a formal sample size could not be calculated because
      no previous microvascular data in dengue exist. FUNDING: Wellcome Trust.

PMID- 26312833
TI  - Revascularisation of renal artery stenosis as a therapy for heart failure: an
      observational cohort study.
AB  - BACKGROUND: Heart failure contributes to 5% of all hospital admissions, and
      mortality is more than 50% at 4 years. 54% of patients with a left ventricular
      ejection fraction of less than 40% have renal artery stenosis. The potential
      benefit of revascularisation for heart failure is not established. We aimed to
      compare clinical outcomes for renal artery revascularisation with medical therapy
      for renal artery stenosis associated with heart failure as the first step towards
      validating revascularisation as a therapeutic option in heart failure. METHODS:
      In a prospective, longitudinal observational study at a single UK nephrology
      centre, we recruited patients with atherosclerotic renal artery stenosis (>50% as
      judged by CT, MR, or direct angiography). Endpoints were all-cause mortality and
      hospital admission for heart failure. Survival analyses were performed with Cox
      proportional hazard model adjusted for age, estimated glomerular filtration rate
      (eGFR), and cardiovascular comorbidities. Ethics approval was granted by South
      Manchester Research Ethics Committe. FINDINGS: 611 patients (152 [25%] with and
      459 [75%] without heart failure) were recruited. Mean age was 70 years (SD 9),
      348 (57%) were men, 183 (30%) had diabetes, and mean eGFR was 33 mL/min per 1.73
      m(2) (SD 19). Patients with and without heart failure were similar with to sex,
      diabetes, and eGFR. 367 participants (60%) died over a follow-up of a mean of 4.3
      years (SD 3.6). 87 patients without heart failure (19%) underwent
      revascularisation compared with 47 with heart failure (31%). The adjusted hazard
      ratio (HR) for death in heart failure compared with no heart failure was 1.9 (95%
      CI 1.5-2.5, p<0.0001). For patients without heart failure, the adjusted HR for
      death in revascularisation compared with receiving medical therapy was 0.8 (0.5
      1.1, p=0.16). For heart failure, the HR was 0.6 (0.3-0.9, p=0.01). The HR for
      hospital admission for heart failure in revascularised patients was 0.2 (0.0-1.1,
      p=0.06). INTERPRETATION: Revascularisation of renal artery stenosis in heart
      failure is associated with a substantial reduction in all-cause mortality and
      hospital admission, although such observational data might be complicated by
      hidden confounders. These findings are encouraging for the development of a
      randomised trial of renal artery revascularisation versus medical therapy in
      heart failure, and suggest that investigation for renal artery stenosis should be
      considered more frequently in heart failure clinics. FUNDING: None.

PMID- 26312834
TI  - Role of melanocortin signalling in the preference for dietary macronutrients in
      human beings.
AB  - BACKGROUND: Signalling though the melanocortin 4 receptor (MC4R), which is widely
      expressed in the hypothalamus, mediates food intake and macronutrient preference
      in rodents. Studies in patients with MC4R deficiency can provide insights into
      the role of this pathway in man. We investigated the role of melanocortin
      signalling in fat and sucrose preference in human beings by studying patients
      with loss of function mutations in MC4R. METHODS: We studied 24 obese patients
      with MC4R deficiency, and 80 healthy controls (40 obese, 40 lean). We used an ad
      libitum meal protocol consisting of three meals covertly manipulated to provide
      20% (low), 40% (medium), and 60% (high) fat content. We used the same procedure
      for meals manipulated to provide 8% (low), 26% (medium), and 54% (high) sucrose
      content. We measured food intake and rated liking for the meals with visual
      analogue scores. Data were analysed by ANOVA and Tukey's post-hoc tests or a
      linear mixed-effects model with an interaction term for study group and study
      meal when appropriate. FINDINGS: Although the liking of the three different fat
      meals did not differ between the three groups, patients with MC4R mutations
      consumed 95% more of the high fat meal than did lean controls and 65% more of the
      high fat meal than did obese controls (p=0.0222 for the interaction of group by
      meal). By contrast, although liking ratings for low and medium sucrose meals were
      comparable in the individuals with MC4R deficiency, liking ratings for the high
      sucrose meal were significantly reduced (p=0.0252 in linear mixed-effects model,
      intercept 57.8, MC4R group factor -26.2, factors in the model for MC4R-low
      sucrose 27.7, MC4R-medium sucrose 22.6). Similarly, patients with MC4R deficiency
      consumed less of all three sucrose meals than did healthy controls (p=0.0064).
      INTERPRETATION: Our study shows that the central melanocortin system has
      divergent effects on macronutrient preference and intake in human beings.
      FUNDING: Wellcome Trust, NIHR Cambridge Biomedical Research Centre, Bernard Wolfe
      Health Neuroscience Fund, NeuroFAST consortium, which is funded by the European
      Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no
      245009.

PMID- 26312835
TI  - Genetic variants associated with non-typhoidal Salmonella bacteraemia in African
      children.
AB  - BACKGROUND: Non-typhoidal Salmonella (NTS) causes invasive and frequently fatal
      disease in African children. Existing strategies to prevent, diagnose, and treat
      NTS disease are inadequate. An improved understanding of the biology of invasive
      Salmonella infection will facilitate the development of novel NTS control
      measures. Despite evidence in mice and man showing a clear role for host genetics
      in NTS susceptibility, there are no published studies investigating host genetic
      susceptibility to NTS in African populations. METHODS: We conducted a genome-wide
      association study (SNP Array 6.0, Affymetrix, CA, USA) of NTS bacteraemia in
      Kenyan children, with replication in Malawian children. We assessed the function
      of NTS-associated variants in an expression quantitative trait locus (eQTL)
      dataset of interferon gamma (IFNgamma) and lipopolysaccharide-stimulated
      monocytes from 432 healthy European adults. Serum IFNgamma (Bio-Plex immunoassay,
      Bio-Rad Laboratories, CA, USA) in Malawian NTS cases (n=106) during acute disease
      was correlated with genotype by linear regression. FINDINGS: After whole-genome
      imputation and quality control, 180 Kenyan cases and 2677 controls were included
      in an association analysis at 7 951 614 (additive model) and 4 669 537 (genotypic
      model) loci. After quality control, 143 Malawian cases and 336 controls were
      included in the replication analysis. An intronic variant in STAT4 was associated
      (recessive model) with NTS in both Kenyan and Malawian children (Kenya p=5.6 *
      10(-9), Malawi p=0.02, combined p=1.4 * 10(-9); odds ratio 7.2, 95% CI 3.8-13.5).
      The NTS-associated variant was an eQTL for STAT4 expression in IFNgamma
      stimulated monocytes (p=9.59 * 10(-6)), the NTS risk allele being associated with
      lower STAT4 expression. In Malawian children with NTS bacteraemia, the same NTS
      risk allele was associated with lower serum concentrations of IFNgamma (p=0.02)
      at presentation. INTERPRETATION: STAT4 is highly plausible as a susceptibility
      locus for invasive NTS disease. STAT4 mediates IFNgamma release in T cells and
      natural killer cells in response to interleukin 12 (IL12). Individuals with rare
      mutations elsewhere in the IL12-IFNgamma axis are at risk of disseminated NTS
      infection. We provide the first evidence, to our knowledge, of a host genetic
      determinant of NTS disease in African children, and of a STAT4 variant conferring
      susceptibility to an infectious disease in man. FUNDING: Wellcome Trust.

PMID- 26312836
TI  - Retinal development in albinism: a prospective study using optical coherence
      tomography in infants and young children.
AB  - BACKGROUND: Retinal development normally involves migration of the inner retinal
      layers away from the fovea, migration of the cone photoreceptors into the fovea,
      and elongation of the photoreceptors over time. This process is arrested
      prematurely in albinism. However, because retinal development continues at least
      until the age of 4 years, when development arrests in albinism is uncertain. In
      this study we outlined the time course of retinal development in children with
      albinism. METHODS: We studied 44 children with a diagnosis of albinism and 223
      control participants. All participants were aged between 0 and 6 years. We
      obtained 219 mixed cross-sectional and longitudinal optical coherence tomography
      examinations in the albinism group and compared them with 558 control
      examinations. Retinal layer segmentation was performed with ImageJ software.
      Generalised linear mixed regression modelling was used to analyse group
      differences in retinal development. FINDINGS: In the albinism group, inner
      retinal layer migration from the fovea was delayed and arrested prematurely,
      resulting in a significantly thicker central macular thickness than in the
      control group (p<0.0001). Whereas the central macular thickness increased with
      age in the control group, in the albinism group it initially decreased with age
      as a result of continuing regression of the inner retinal layers (p=0.041). The
      perifoveal retinal thickness was significantly decreased in albinism from a
      reduction of both inner (p<0.0001) and outer (p<0.0001) retinal layer
      thicknesses. There was evidence that the photoreceptor layers across the fovea
      were elongating in albinism, albeit at a reduced rate, compared with the control
      group. This difference was most apparent for the foveal photoreceptor inner
      segment (p=0.001). INTERPRETATION: Our findings show that perturbations exist in
      several aspects of retinal development including the migration and
      differentiation of the neuronal cells within the retina. We showed continuing
      regression of the inner retinal layers and elongation of the photoreceptor layers
      suggesting residual plasticity of the developing albino retina. This finding is
      important because treatment at the earliest stages of the condition might
      normalise retinal development and optimise vision. FUNDING: UK Medical Research
      Council (grant number MR/J004189/1), Ulverscroft Foundation, National Eye
      Research Centre, Nystagmus Network UK.

PMID- 26312837
TI  - The role of TP53 in miRNA loading onto AGO2 and in remodelling the miRNA-mRNA
      interaction network.
AB  - BACKGROUND: DNA damage transactivates tumour protein p53 (TP53)-regulated
      surveillance, crucial in suppressing tumorigenesis. TP53 mediates this process
      directly by transcriptionally modulating gene and microRNA (miRNA) expression and
      indirectly by regulating miRNA biogenesis. However, the role of TP53 in
      regulating miRNA-AGO2 loading and global changes in AGO2 binding to its gene
      targets in response to DNA damage are unknown. These processes might be novel
      mechanisms by which TP53 regulates miRNAs in response to DNA damage. METHODS: To
      show the network of miRNA-mRNA interactions that occur in response to DNA damage,
      we stimulated TP53 wild-type and null cell-lines with doxorubicin and performed
      RNA sequencing from total RNA (RNA-Seq) and AGO2-immunoprecipitated RNA (AGO2-RIP
      Seq). We used a combined AGO2 RIP-seq and AGO2 PAR-CLIP-seq (photoactivatable
      ribonucleoside-enhanced cross-linking and immunoprecipitation) approach to
      determine the exact sites of interaction between the AGO2-bound miRNAs and their
      mRNA targets. FINDINGS: TP53 directly associated with AGO2, and induced and
      reduced loading of a subset of miRNAs, including the lethal 7 (let-7) miRNA
      family members, onto AGO2 in response to DNA damage. Although mutated TP53
      maintained its capacity to interact with AGO2, it mediated unloading instead of
      loading of let-7 family miRNAs, thereby reducing their activity. We determined
      the miRNA-mRNA interaction networks involved in the response to DNA damage both
      in the presence and absence of TP53. Furthermore, we showed that miRNAs whose
      cellular abundance or differential loading onto AGO2 was regulated by TP53 were
      involved in an intricate network of regulatory feedback and feedforward circuits
      that fine-tuned gene expression levels in response to DNA damage to permit the
      repair of DNA damage or initiation of programmed cell death. INTERPRETATION:
      Control of AGO2 loading by TP53 is a new mechanism of miRNA regulation in
      carcinogenesis. FUNDING: UK Medical Research Council, Action Against Cancer.

PMID- 26312838
TI  - Effect of insulin on AKR1C3 expression in female adipose tissue: in-vivo and in
      vitro study of adipose androgen generation in polycystic ovary syndrome.
AB  - BACKGROUND: Insulin resistance and hyperandrogenism are the cardinal features of
      polycystic ovary syndrome (PCOS). Women with insulin receptor (INSR) mutations
      develop severe hyperandrogenism secondary to hyperinsulinaemia. We hypothesised
      that insulin might drive adipose testosterone generation from androstenedione
      through aldoketoredutase type 3 (AKR1C3) in women with insulin resistance. Here
      we assessed the effect of insulin on AKR1C3 activity in vivo and in vitro.
      METHODS: Ten women with PCOS, ten healthy controls, and three women with INSR
      mutations underwent dehydroepiandrosterone (DHEA) challenge; serum androgens were
      measured every 30 min for 4 h after ingestion of 100 mg DHEA. Additionally,
      paired subcutaneous and omental fat samples were obtained during abdominal
      surgery from 38 women. AKR1C3 expression was measured by real-time PCR. Serum
      steroids and cultured cell media androgens were measured with liquid
      chromatography tandem mass spectrometry. FINDINGS: Women with PCOS had higher
      androstenedione concentrations than did controls and women with INSR mutations
      (p=0.01 and p=0.005, respectively). However, area under the curve for
      testosterone was higher in women with INSR mutations after DHEA than in women
      with PCOS and controls (874.2 [SE 242] vs 425 [136] and 375.2 [109], p<0.001 for
      both). AKR1C3 mRNA expression was significantly higher in subcutaneous than in
      omental adipose tissue (p=0.004). AKR1C3 expression correlated positively with
      body-mass index in subcutaneous fat (Spearman correlation=0.51, p=0.006). Insulin
      significantly increased AKR1C3 expression in differentiated subcutaneous
      adipocytes (p=0.04). Incubation with insulin significantly increased testosterone
      generation from androstenedione in cultured subcutaneous cell media compared with
      controls (p<0.001). INTERPRETATION: We have found in-vivo and in-vitro evidence
      of modulation of AKR1C3 activity by insulin in PCOS and in women with INSR
      mutations. Insulin seems to drive adipose androgen generation by increasing
      AKR1C3 activity in female subcutaneous adipose tissue. Selective AKR1C3
      inhibition might offer a novel therapeutic target to reduce androgen burden and
      improve metabolic phenotype in PCOS. FUNDING: Wellcome Trust.

PMID- 26312839
TI  - Targeting indirect pathway CD4 T-cell alloresponses in the prevention of chronic
      transplant rejection.
AB  - BACKGROUND: Uniquely, alloantigen is recognised by two pathways: as intact
      antigen on the surface of donor antigen-presenting cells (direct) and as self
      restricted processed allopeptide (indirect). The indirect pathway is believed to
      be longlasting, and is generally considered to be a single entity. Here we
      address how indirect responses against different alloantigens differ in their
      strength and longevity, and how this knowledge could be used to direct
      immunoregulatory therapy with antigen-specific regulatory T cells (Tregs).
      METHODS: A murine model of cardiac transplantation was used (bm12.Kd.IE to
      C57BL/6). Indirect CD4 T-cell allorecognition of mismatched donor MHC class I and
      II, and of H-Y minor histocompatibility antigen was assessed by quantifying
      proliferation of adoptively transferred monoclonal T-cell receptor transgenic T
      cells (TCR75, Tea, Mar). Antigen presentation by dendritic cells and B cells was
      assessed by selective depletion with diphtheria toxin or depleting anti-CD20
      monoclonal antibody. Tregs were generated by in-vitro culture. FINDINGS: Indirect
      pathway responses were heterogeneous. Whereas the indirect response against class
      I alloantigen was longlasting and persistently strong, the response against class
      II alloantigen decayed within 2 weeks. Leucocyte depletion studies confirmed that
      this difference was due to rapid destruction of MHC class II expressing donor B
      cells and dendritic cells in the recipient, whereas anti-class I responses were
      generated by continual processing of graft parenchymal cells; recognition of
      donor haemopoietic fraction was not required. Notably, transfer of MHC class I
      specific Tregs at transplant or 3 weeks later abrogated germinal centre
      alloantibody responses and blocked development of allograft vasculopathy, whereas
      class II specific Tregs were ineffective when transferred at the late timepoint.
      INTERPRETATION: Although indirect allorecognition is considered to be a single
      entity, our results show that it consists of a number of responses that vary in
      duration and strength according to target alloantigen. The ability of class I
      allopeptide specific Tregs, but not class II specific Tregs, to prevent rejection
      when transferred at a late timepoint suggests that antigen-specific targeting of
      dominant and longlasting pathways might be particularly effective at preventing
      chronic rejection. FUNDING: Wellcome Trust Clinical Research Training Fellowship.

PMID- 26312840
TI  - Recipient natural killer cell allorecognition of passenger donor lymphocytes and
      its effect on adaptive alloimmunity after transplantation.
AB  - BACKGROUND: Memory T cells are known to reside in peripheral non-lymphoid tissue,
      but how their presence within solid organ allografts affects transplant outcomes
      is not known. We have previously described how graft-versus-host (GVH)
      allorecognition by passenger CD4 T cells within MHC class II-mismatched bm12
      heart grafts provokes antinuclear humoral autoimmunity in C57BL/6 recipient mice.
      Here we aimed to examine how such GVH recognition affects the alloresponse to
      allografts with greater mismatching. METHODS: A MHC class I and II mismatched
      murine model of cardiac transplantation was developed (bm12.Kd.IE to C57BL/6).
      After transplantation, cellular and humoral responses against mismatched antigens
      were measured with ELISPOT and ELISA, and the effect of GVH recognition assessed
      by depletion of donor CD4 T cells before graft procurement. Antinuclear
      autoantibody development was assessedwith HeP-2 indirect immunofluorescence. The
      role of recipient natural killer (NK) cells was examined by depletion with anti
      NK1.1 antibody. FINDINGS: Bm12.Kd.IE heart grafts provoked strong germinal centre
      alloantibody and autoantibody responses in C57BL/6 recipients and developed
      allograft vasculopathy. By contrast, heart grafts from CD4 T-cell-depleted donors
      developed only minimal vasculopathy, and the alloantibody responses were weaker,
      without observable autoantibody. Bm12.Kd.IE CD4 T cells survived long term when
      transferred to RAG hosts suggesting that avoidance of killing by host NK cells
      might be essential for autoantibody development. In support, in a model of
      alloantibody-mediated vasculopathy, depletion of NK cells from a C57BL/6
      recipient of a BALB/c heart graft resulted in the development of autoantibody,
      amplification of the alloantibody response, and rapid allograft rejection. This
      amplification was abrogated by depletion of donor CD4 T cells. INTERPRETATION:
      Although host adaptive immunity is expected to bring about destruction of
      passenger lymphocytes within heart allografts, this process occurs too slowly to
      prevent GVH-mediated augmentation of the alloresponse to the graft. Rather, rapid
      killing of donor lymphocytes by host alloreactive NK cells is essential.
      Passenger CD4 lymphocytes might therefore contribute to chronic rejection in
      recipients receiving an allograft that does not prompt innate NK cell
      recognition. FUNDING: Wellcome Trust Clinical Research Training Fellowship.

PMID- 26312841
TI  - Effect of platelet-rich plasma on healing tissues in acute ruptured Achilles
      tendon: a human immunohistochemistry study.
AB  - BACKGROUND: Platelet-rich plasma (PRP), an autologous derivative of whole blood
      that contains a supraphysiological concentration of platelets, is thought to
      invoke an earlier and improved tissue healing response. This notion has been
      supported by in-vitro and animal studies in bone, cartilage, tendon, and muscle.
      To our knowledge no published study exists of the effects of PRP in human tissues
      in vivo. The aim of our study was to investigate the response of ruptured
      Achilles tendon treated with PRP. METHODS: Tendon tissue biopsy samples were
      obtained from 20 patients with ruptured Achilles tendon by means of ultrasound
      guided needle biopsies from the healing area of the Achilles tendon 6 weeks after
      treatment with PRP or placebo controls (10 patients each). All samples were
      embedded in paraffin wax, sectioned, and stained with haematoxylin and eosin and
      alcian blue. Immunohistochemistry markers were used to identify collagen I and
      III, lymphocytes (CD45), proliferation (KI67), and blood vessels (CD34). All
      images were masked and analysed with Image J software. FINDINGS: Cellularity and
      glycosaminoglycans content were significantly higher in PRP-treated tendons than
      in controls (p=0.01 and p<0.001, respectively). Fibre structure of the tissue was
      significantly better in the PRP group than in the control tissue (p<0.001).
      Although both groups showed high collagen I staining, content of collagen I was
      significantly higher in PRP-treated tendons than in control tendons (p=0.0079),
      whereas collagen III content was not different (p=1.0). The ratio of collagen III
      to collagen I was significantly lower in PRP samples (p=0.007). There was no
      significant difference in CD45 expression (p=0.33). However, PRP samples had
      fewer blood vessels than did control samples (p=0.023). The overall modified
      Bonar score was significantly lower in PRP samples, which indicates improved
      early tendon healing. INTERPRETATION: This is the first study, to our knowledge,
      to report the immunohistochemical response of ruptured human Achilles tendon to
      PRP. The findings reveal that locally applied PRP enhanced the maturity of the
      healing tendon tissues by promoting better collagen I deposition, decreased
      cellularity, less vascularity, and higher glycosaminoglycan content when compared
      with control samples. Further work is required to determine the longer term
      effects of the use of PRP in musculoskeletal diseases. FUNDING: National
      Institute for Health Research.

PMID- 26312842
TI  - Effect of anandamide on endometrial adenocarcinoma (Ishikawa) cell numbers:
      implications for endometrial cancer therapy.
AB  - BACKGROUND: We have previously shown that patients with endometrial carcinoma
      express elevated concentrations of the endocannabinoid, anandamide (AEA), in both
      their plasma and their endometrial tissue and that the endometrial carcinoma cell
      line, Ishikawa, contains the receptors to which AEA binds. Several studies have
      reported that human and rodent cancer cell lines die in response to high AEA
      concentrations. The incidence of endometrial carcinoma continues to escalate and,
      although surgical treatment has improved, morbidity and mortality rates have not.
      A move towards a novel non-surgical therapeutic option is thus required, and the
      endocannabinoid system provides a good candidate target. We aimed to investigate
      the effects of AEA on the survival and proliferation of an endometrial carcinoma
      cell model. METHODS: This prospective basic research study was conducted at a UK
      teaching hospital. Ishikawa cells were cultured in vitro, and a range of AEA
      concentrations (0-10 000 nM) were added to the cells. The effect of AEA was
      measured at different timepoints (4, 18, 24, 48, and 72 h). Primary outcome was
      cell proliferation and cell viability as measured with a commercial proliferation
      apoptosis assay in which assay colour at 420 nm is directly proportional to cell
      density. One-way ANOVA was performed with Prism (version 7). FINDINGS: Ishikawa
      cells were sensitive to AEA-mediated cytotoxicity in a pseudo dose-dependent
      manner. AEA caused a significant decrease in cell number only at concentrations
      above 1000 nM (mean 28.1% [SE 7.8], n=12; p<0.0001). The decrease in cell
      viability that occurred at 4, 18, and 24 h was partly restored at 48 and 72 h
      suggesting that the AEA growth inhibitory effect is time limiting.
      INTERPRETATION: Our results show that AEA induces a decrease in Ishikawa cell
      number probably through inhibition of cell proliferation rather than cell death.
      These data suggest that the increased plasma and tissue AEA concentrations
      observed in patients with endometrial cancer is a counter mechanism against
      further cancer growth and points to the endocannabinoid system as a potentially
      new therapeutic target. FUNDING: University Hospitals of Leicester NHS Trust.

PMID- 26312843
TI  - Pleiotropic effects of statins in hypercholesterolaemia: a prospective
      observational study using a lipoproteomic based approach.
AB  - BACKGROUND: The benefit of statins in the prevention of cardiovascular disease is
      well founded, derived from their lipid lowering and pleiotropic effects. The
      concept of lipoproteins as lipid transporters has evolved to encompass functions
      in coagulation, inflammation, and redox reactions due to their unique protein
      cargo. The aim of this study was to determine the effect of statin therapy on
      lipoproteins and their protein cargo by use of an unbiased bottom-up proteomics
      approach in people with hypercholesterolaemia. METHODS: 11 people fulfilling the
      inclusion criteria were recruited into this UK-based single centre prospective
      observational study. They were started on statins for primary prevention. Blood
      was withdrawn at baseline and after a minimum of 2 months of statin therapy.
      Plasma was co-incubated with a lipoaffinity resin. Isolated proteins were
      digested and analysed with label-free two-dimensional liquid chromatography
      coupled to electrospray high-definition ion mobility tandem mass spectrometry.
      FINDINGS: 218 proteins were identified with Progenesis QI software, with 33
      proteins demonstrating significant differential expression between the pre-statin
      and the on-statin samples (each p<0.05). 17 proteins were upregulated by statin
      therapy, including proteins concerned with cytoskeletal organisation (vinculin
      p<0.0001, tropomyosin alpha4 p=0.0108), antioxidative (peroxiredoxin 2 p=0.0092),
      and anti-inflammatory effects (transgelin-2 p=0.0071). Apolipoprotein B100 was
      downregulated by statin therapy, consistent with it mechanism of action
      (p=0.0006). Statin therapy downregulated novel proteins concerned with the
      modulation of pancreatic beta-cell function (adipsin p=0.0056) and haemopoietic
      precursor proliferation (stem cell growth factor p<0.0001). INTERPRETATION: Our
      findings show that statins remodel the cytoskeletal architecture and mediate
      various anti-inflammatory, antioxidant, and antiproliferative effects that might
      limit endothelial dysfunction. The downregulation of adipsin, a novel adipokine
      that stimulates insulin secretion, could explain the controversial link between
      statin use and the development of diabetes. This study extends our understanding
      of the beneficial and harmful pleiotropic effects of statin therapy. FUNDING:
      British Heart Foundation.

PMID- 26312844
TI  - Acute alcoholic hepatitis and cellular Th1 immune responses to alcohol
      dehydrogenase.
AB  - BACKGROUND: Alcoholic hepatitis is characterised by florid hepatic inflammation,
      liver failure, and death within 28 days in 35% of patients. We recently showed
      proliferative peripheral blood mononuclear cell (PBMC) responses to alcohol
      dehydrogenase (ADH) in patients with alcohol-related cirrhosis, associated with T
      helper-type 1 (Th1) immunity and disease severity. We aimed to define whether ADH
      specific cellular immunity is present in alcoholic hepatitis. METHODS: PBMCs were
      collected from 15 patients with alcoholic hepatitis (modified Maddrey's
      discriminant function >32), nine with alcohol-related cirrhosis (long-term
      alcohol abstinence), and three healthy controls. 25 overlapping peptides,
      spanning the human ADH beta1 subunit, were constructed. Proliferation to ADH
      peptides (1 * 10(5) cells per well, cultured with 10 mM peptides for 7 days) was
      assessed by (3)H-thymidine incorporation. A stimulation index (SI) of 2.5 or more
      was regarded as positive. ELISA measured concentrations of interferon gamma
      (IFNgamma), interleukin (IL) 17, and IL4 from supernatant. FINDINGS: PBMCs from
      seven of 15 patients with alcoholic hepatitis recognised one to three ADH
      peptides (SI <=5.7). IFNgamma (mean 390.9 pg/mL [SE 31.4]) was detected in 48% of
      wells, IL17 (20.1 [3 .4]) in 15%, and IL4 (90.5 [9.3]) in 14%. PBMCs from six of
      the nine patients with alcohol-related cirrhosis recognised one to five peptides
      (SI <=5.2). IFNgamma (360.7 [58.9], p>0.05) was detected in 31% of wells, IL17
      (57.7 [10.9], p=0.0006) in 19%, and IL4 (219.7 [11.2], p=0.0012) in 28%. PBMCs
      from two healthy controls recognised one to two peptides (SI <=3.1); all cytokine
      levels were below baseline. INTERPRETATION: Proliferative anti-ADH immune
      responses in alcoholic hepatitis focused on individual epitopic regions.
      Predominance of proinflammatory Th1 responses was more pronounced in alcoholic
      hepatitis than in alcoholic-related cirrhosis. This finding requires
      investigation of targeted therapies to inhibit Th1 immunity in alcoholic
      hepatitis. FUNDING: Wellcome Trust.

PMID- 26312845
TI  - CD57 expression in CD8 T cells and development of cutaneous squamous cell
      carcinoma in renal transplant recipients: a prospective cohort study.
AB  - BACKGROUND: Cutaneous squamous cell carcinoma is the most common malignancy in
      renal transplant recipients and a major cause of morbidity and mortality. Various
      measures have been proposed to identify recipients at increased risk of
      developing this cancer to allow targeted intervention. CD57 expression might
      represent a marker of T-cell exhaustion; we hypothesised that expression could
      predict development of squamous cell carcinoma in renal transplant recipients,
      and undertook a prospective cohort study to assess its predictive value. METHODS:
      Renal transplant recipients with and without previous squamous cell carcinoma
      (matched by race, age, sex, and immunosuppression duration) were recruited at
      routine clinical follow-up. Peripheral blood lymphocytes were analysed by flow
      cytometry. Three previously developed risk scores (Harden, Urwin, and Harwood),
      based on clinical phenotype, were also evaluated. The outcome event was
      histologically diagnosed squamous cell carcinoma during the study. Ethics
      approval was granted by local committee. Hazard ratios (HR) were calculated by
      Cox regression. FINDINGS: 57 renal transplant recipients with and 53 without
      previous squamous cell carcinoma were recruited. During a median follow-up of 309
      days (IQR 223-409), 20 recipients developed this cancer (including four with a
      first diagnosis). On univariate analysis increasing age at enrolment, previous
      squamous cell carcinoma, having the CD57hi phenotype (>=50% of CD8 T cells
      expressing CD57), and increasing clinical risk score were predictive of cancer
      development. However, all three clinical risk scores were no longer predictive
      when adjusted for age. By contrast, transplant recipients displaying CD57hi were
      at significantly increased risk of future squamous cell carcinoma compared with
      CD57lo recipients (<=50% of CD8 T cells expressing CD57) (HR 5.0, 95%CI 1.11
      22.3; p=0.04); risk remained significant after adjustment for both age (1.1, 1.0
      1.1; p=0.04) and history of previous squamous cell carcinoma (3.5, 1.12-11.2;
      p=0.04). INTERPRETATION: Our results show that the CD57hi phenotype is a stronger
      predictor of squamous cell carcinoma development in long-term, at-risk renal
      transplant recipients than previously identified clinical phenotypes. This
      finding could help in the identification of renal transplant recipients at high
      risk of this cancer, who would benefit from intensive dermatological screening
      and immunosuppression reduction. FUNDING: Wellcome Trust, Oxford University
      Hospitals Research Services Committee.

PMID- 26312846
TI  - The influence of school in the development of eating disorders: a record-linkage
      study.
AB  - BACKGROUND: Clinical impression is that rates of eating disorders vary between
      schools; we are not aware of any previous research on this topic. We aimed to
      investigate whether rates of eating disorders in 16-20-year-old girls vary
      between upper secondary schools, and to test the hypothesis that school
      characteristics are associated with rates of eating disorders, even after
      accounting for characteristics of individual students. METHODS: This multilevel
      longitudinal study made use of record-linkage data from Stockholm County, Sweden.
      Participants were 55 824 Swedish-born girls completing secondary education in
      2001-10 at 409 schools. Outcome was any diagnosed eating disorder at 16-20 years,
      as defined by an ICD (9 or 10) or DSM-IV code, or inferred from an appointment at
      a specialist eating disorder clinic. Multilevel modelling was used to separate
      individual and school level effects. The Stockholm Regional Ethical Review Board
      approved the study. FINDINGS: A 4.4% variation in incidence of eating disorders
      between schools was seen; after taking individual risk factors into account
      variation between schools was 2.9% (95% CI 1.5-5.0). Schools with a higher
      proportions of girls than boys had an increased incidence of eating disorders:
      for each 10% increase in the proportion of girls at a school, the odds ratio for
      eating disorders was 1.07 (95% CI 1.01-1.13, p=0.017). For each 10% increase in
      the proportion of parents with post-secondary education, the odds ratio for
      eating disorders was 1.14 (1.09-1.19, p<0.0001). INTERPRETATION: Our findings
      show that the contextual aspects of a school environment are associated with
      increased incidence of eating disorders. Incidence rates of eating disorders are
      higher in schools characterised by a high proportion of female students and of
      students with highly educated parents. To our knowledge, this is the first study
      to investigate whether rates of eating disorders vary between schools; however,
      use of registry data means that individuals who did not seek treatment would not
      have been studied. FUNDING: HB was supported by a Wellcome Trust Institutional
      Strategic Support Fund (via the Elizabeth Blackwell Institute).

PMID- 26312847
TI  - Role of retinoic acid in the stability of the T-helper-type 1 lineage and
      implications for autoimmunity.
AB  - BACKGROUND: CD4 T cells with features of both T-helper-type 1 (Th1) and 17 (Th17)
      cells have been implicated in several autoimmune diseases suggesting that
      plasticity among CD4 T-cell lineages is potentially pathogenic. However, the
      factors that regulate T-cell lineage stability are largely unknown. Retinoic acid
      (RA) is synthesised at sites of inflammation. We hypothesised that retinoic acid,
      a profound epigenetic modifier, could regulate T-cell lineage stability. METHODS:
      We used a mouse model in which retinoic acid signalling is specifically ablated
      within the T-cell compartment through overexpression of a dominant negative
      retinoic acid receptor alpha (RARalpha) (dnRARalpha mice) to investigate its role
      in the regulation of Th1 lineage stability. Genome-wide ChIP-seq analysis was
      done to identify RARalpha targets. In parallel, we performed global mapping of
      regulatory regions, termed enhancers, to gain mechanistic insight into retinoic
      acid regulation of T-cell fate. The in-vivo relevance of our findings was
      determined in a model of oral antigen-induced intestinal inflammation. FINDINGS:
      We found that retinoic acid is crucial for maintenance of the Th1 lineage.
      Abrogation of retinoic acid signalling in Th1 cells resulted in loss of T-bet
      expression and STAT4 activity. Th1 cells from dnRARalpha mice showed enhanced
      plasticity with the emergence of hybrid Th1-Th17 and Th17 effector cells. Global
      analysis of RARalpha binding and enhancer mapping revealed that RA-RARalpha
      directly regulated enhancer activity at Th1 lineage defining genes while
      repressing genes that regulate Th17 cell fate. Retinoic acid inhibition of Th1
      plasticity was essential for maintaining appropriate Th cell responses in vivo
      and preventing autoimmune intestinal inflammation. INTERPRETATION: Our study has
      identified RA-RARalpha as a key component of the regulatory network governing
      maintenance and plasticity of Th1 cells and defines a new pathway for the
      development of pathogenic Th17 cells. Retinoids might be novel therapeutic agents
      for Th17-associated autoimmune diseases. FUNDING: Wellcome Trust.

PMID- 26312848
TI  - Identification of novel biomarkers in plasma for prediction of treatment response
      in patients with heart failure.
AB  - BACKGROUND: Heart failure is a complex clinical syndrome that occurs at the end
      stage of heart disease. Despite advances in therapy for heart failure,
      improvement of clinical outcomes remains a challenge for physicians. The
      identification of treatment response early in the course of disease would be
      useful to improve management of these patients. The aim of this study was to
      identify novel biomarkers in plasma that could predict treatment response in
      patients with heart failure. METHODS: Patients with heart failure who met
      inclusion and exclusion criteria according to the guidelines of the European
      Society of Cardiology were recruited. Uptitration of angiotensin-converting
      enzyme inhibitors and beta blockers was performed over 6 months. Patients were
      followed up for clinical events within the next 24 months. Plasma proteins in
      patients who responded to standard treatment (responders) were compared with
      patients who died or were re-admitted for heart failure (non-responders). Plasma
      samples were depleted of 14 high abundance proteins with a multiple affinity
      removal system column (MARS). Then plasma samples were analysed on two
      dimensional liquid chromatography coupled to a tandem mass spectrometry (2D LC
      ESI-MS/MS) in high definition mode (HDMS(E)) to identify and quantify the
      different expression of proteins in plasma. Finally, ELISA was used to verify
      candidate biomarkers. FINDINGS: Participants were 100 patients with heart failure
      matched for sex and age (50 responders [25 women], 50 non-responders [25 women],
      mean age 76.6 years [SD 8.1]). Of the non-responders, 18 died and 32 were re
      admitted to hospital. 2D LC-ESI-MS/MS showed that the expression of neurotrimin
      (NTM) was highly upregulated, by 26.5 times (p<0.0001), in the responder group
      compared with the non-responder group. ELISA in the verification phase showed
      that the concentrations of NTM in plasma were significantly higher in the
      responders and lower in the non-responders (mean 4.73 log10 relative light units
      [SD 0.07] vs 4.70 [0.08], p=0.036). When ANOVA with Bonferroni post-hoc
      comparisons was used in three outcome subgroups (responders, patients re-admitted
      to hospital, and deaths), NTM concentrations were significantly different between
      death and the other groups (higher in responder vs death group, p<0.0001; higher
      in re-admission vs death group, p=0.001). INTERPRETATION: Our findings suggest
      that NTM as a novel biomarker in heart failure will not only add information to
      understand the pathophysiological mechanisms of heart failure better, but also
      might provide a more accurate prediction of treatment response to guide medical
      therapy. In addition, a novel therapeutic target could be identified for design
      of drugs to improve outcomes. Futher work is required in larger populations to
      confirm this biomarker. FUNDING: European Union's Seventh Framework Programme
      (BIOSTAT-CHF), John and Lucille van Geest Foundation.

PMID- 26312849
TI  - The skin microbiome in psoriatic arthritis: methodology development and pilot
      data.
AB  - BACKGROUND: Skin microbiota are likely to be important in the development of
      conditions such as psoriatic arthritis. Profiling the bacterial community in the
      psosriatic plaques will contribute to our understanding of the role of the skin
      microbiome in these conditions. The aim of this work was to determine the optimum
      study design for work on the skin microbiome with use of the MiSeq platform. The
      objectives were to compare data generated from two platforms for two primer pairs
      in a low density mock bacterial community. METHODS: DNA was obtained from two low
      density mock communities of 11 diverse bacterial strains (with and without human
      DNA supplementation) and from swabs taken from the skin of four healthy
      volunteers. The DNA was amplified with primer pairs covering hypervariable
      regions of the 16S rRNA gene: primers 63F and 519R (V1-V3), and 347F and 803R (V3
      V4). The resultant libraries were indexed for the MiSeq and Roche454 platforms
      and sequenced. Both datasets were de-noised, cleaned of chimeras, and analysed by
      use of QIIME software (version 1.8.0). FINDINGS: No significant difference in the
      diversity indices at the phylum and the genus level between the platforms was
      seen. Comparison of the diversity indices for the mock community data for the two
      primer pairs demonstrated that the V3-V4 hypervariable region had significantly
      better capture of bacterial diversity than did the V1-V3 region. Amplification
      with the same primer pairs showed strong concordance within each platform (98.9
      99.8%), with negligible effect of spiked human DNA contamination. Comparison at
      the family level classification between samples processed on the MiSeq and
      Roche454 platforms using the V3-V4 hypervariable region also showed a high level
      of concordance (87%), although less so for the V1-V3 primers (10%). The pilot
      data from healthy volunteers were similar. INTERPRETATION: Results obtained from
      the V3-V4 16S rRNA hypervariable region, sequencing on the MiSeq and Roche454
      platforms, were concordant between replicates, and between each other. These
      findings suggest that the MiSeq platform, and these primers, is a comparable
      method for determining skin microbiota to the widely used Roche454 methodology.
      FUNDING: NIHR Manchester Musculoskeletal Biomedical Research Unit.

PMID- 26312850
TI  - Pharmacokinetics and pharmacodynamics of subcutaneously administered PYY3-36 and
      its analogues in vivo.
AB  - BACKGROUND: Obesity is an emergent epidemic associated with morbidity, mortality,
      and psychosocial effects. One of the key gut hormones that controls appetite is
      peptide tyrosine-tyrosine 3-36 (PYY3-36) whose circulating half-life is only 8
      min. A long-acting analogue of PYY3-36 would therefore have great potential as an
      antiobesity agent. The aims of this study were to investigate the effect of
      various aminoacid modifications of PYY3-36 on pharmacokinetics and their ability
      to suppress food intake. METHODS: To investigate the pharmacokinetics of PYY3-36
      and three modified analogues, serial sampling of plasma peptide levels via
      cannulation of the jugular vein was performed after subcutaneous injection of the
      peptide in rats (n=4 per peptide, 80 nmol/kg). To investigate the effect of these
      peptides on food intake, mice were injected subcutaneously (1000 nmol/kg) and
      food intake was assessed at timed intervals over 24 h (n=8 per peptide).
      FINDINGS: One-way ANOVA with post-hoc Dunnett's test was used in which each
      comparison was with the PYY3-36 or saline group. Plasma concentrations of the
      modified analogue, PYY-AP3H, were significantly higher than PYY3-36 up to 24 h
      post injection (p=0.0008 at 4 h, p=0.0028 at 24 h). The results confirm that
      modification of the native peptide, by addition of an alpha-helix stabilising
      sequence and histidine residues, lengthens the pharmacokinetic profile.
      Furthermore, PYY-AP3H significantly reduced food intake for up to 24 h compared
      with saline (p<0.0001) and native PYY3-36 (p<0.0001). INTERPRETATION: The
      rationally designed analogue, PYY-AP3H, has potential as a once-a-day
      subcutaneously administered preparation for the treatment of obesity. FUNDING: UK
      Medical Research Council, Biotechnology and Biological Sciences Research Council,
      National Institute for Health Research (NIHR), an Integrative Mammalian Biology
      (IMB) Capacity Building award, an FP7-HEALTH-2009-241592 EuroCHIP grant, NIHR
      Imperial Biomedical Research Centre Funding Scheme.

PMID- 26312851
TI  - Does grandparents' diet affect weight and risk of hypogonadism in subsequent
      generations?
AB  - BACKGROUND: Worldwide, obesity has doubled since 1980. WHO declares obesity as
      preventable and attributes the increase in prevalence to high consumption of
      energy-rich foods and decreased physical activity. Epidemiological and
      experimental studies suggest that parents' and grandparents' diet could also have
      a role. We established a model of grandparents' high-fat diet (HFD) to explore
      potential mechanisms. METHODS: Sprague-Dawley rats were fed a HFD (45% fat) or a
      matched control diet (10% fat) from weaning for 14 weeks. After metabolic
      testing, founders (F0) were bred with controls to establish an F1 generation. F1
      rats were maintained on the control diet for 14 weeks after weaning and then
      underwent metabolic testing followed by mating with control rats to generate F2
      offspring. We analysed F0 data with ANOVA and the F1 and F2 data using mixed
      models, with group and sex as a fixed factor and litter as a random factor.
      FINDINGS: F0 male rats (n=11-13) and female rats (n=6-12) were, respectively,
      9.7% (p=0.017) and 14.7% (p=0.001) heavier after 14 weeks' HFD, with a 33.3%
      increase in visceral adiposity (p=0.014). F1 male and female offspring (n=6) of
      HFD mothers were heavier (p=0.034 and 0.01, respectively) than controls. F1
      daughters of HFD fathers were also heavier (p=0.01). F2 male offspring (n=4-7)
      derived from HFD maternal grandfathers were 7.7% heavier (p=0.029), exhibited a
      31% increase in visceral adiposity (p=0.032), a 97% increase in plasma leptin
      (p=0.027), a trend for lower testosterone (p=0.057), and an increase in the
      luteinising hormone to testosterone ratio (p=0.017). F2 male and female rats
      whose maternal grandfather consumed a HFD had reduced insulin sensitivity
      (p<0.0005). INTERPRETATION: Our results show that founder diet affects the
      metabolic and reproductive health of two subsequent generations of rats in a
      grandparent-specific, parent-specific, and sex-specific manner. The causal
      mechanisms remain to be further explored. The present human obesity epidemic
      might thus have a wider aetiology than currently accepted. FUNDING: UK Medical
      Research Council.

PMID- 26312852
TI  - CD4+CD28- T-cell expansions in ANCA-associated vasculitis and association with
      arterial stiffness: baseline data from a randomised controlled trial.
AB  - BACKGROUND: Cardiovascular risk is increased in the anti-neutrophil cytoplasm
      antibody (ANCA)-associated vasculitides (AAV). CD4+CD28- T cells are expanded in
      patients with AAV who are seropositive for cytomegalovirus (CMV), and are
      associated with increased mortality. CMV seropositivity in other conditions is
      associated with arterial stiffness, a marker of cardiovascular risk. We assessed
      whether CD4+CD28- T cells in CMV seropositive patients with AAV are associated
      with arterial stiffness and whether treatment with valaciclovir reduces this cell
      population. METHODS: In this open-label phase 2 trial, patients were randomised
      (1:1) by computer to valaciclovir (8 g daily) or no additional treatment for 6
      months. Primary outcome was proportion of patients with CMV reactivation.
      Arterial stiffness (carotid to femoral pulse wave velocity [PWV]) was measured
      and peripheral blood CD4+CD28- T cells analysed by flow cytometry at baseline and
      6 months. CD4+CD28- T-cell interferon gamma (IFNgamma) secretion was stimulated
      with CMV lysate. Data are presented as median (IQR). Between-group differences
      were tested by Mann-Whitney U test and correlations by Spearman's rank. Analysis
      was by intention to treat. This trial is registered with ClinicalTrials.gov,
      number NCT01633476. FINDINGS: Baseline data are presented from the first 28
      patients enrolled, with 6 months' follow-up completed in five treatment and six
      control patients. More CD4+CD28- than CD4+CD28+ T cells expressed T-bet (83.5%
      [47.5-89.9] vs 12.9 [4.7-22.2], p<0.0001) and secreted IFNgamma after stimulation
      (14.3% [8.4-26.0] vs 0.8 [0.2-1.3], p<0.0001). CX3CR1, a cell surface marker
      whose expression is associated with endothelial dysfunction, was only expressed
      on CD4+CD28- T cells. The proportion of CD4+CD28- T cells correlated with PWV
      (r=0.408, p=0.035). At 6 months, reduction in proportion of CD4+CD28- T cells was
      greater in the treatment than in the control group (-1.8% [-5.2 to -0.6] vs 0.5 [
      0.8 to 2.5], p=0.044). INTERPRETATION: These preliminary results suggest that
      CD4+CD28- T cells in AAV are proinflammatory cells with high expression of the
      fractalkine receptor CX3CR1 that has been implicated in endothelial dysfunction.
      This cell population is associated with arterial stiffness, and its expansion is
      attenuated with valaciclovir treatment. This research has important implications,
      because cardiovascular disease is a major cause of mortality in AAV. FUNDING:
      Wellcome Trust, Vasculitis UK.

PMID- 26312853
TI  - Topical emollient for prevention of infection in preterm infants: a systematic
      review.
AB  - BACKGROUND: Breakdown of the developmentally immature epidermal barrier in the
      preterm infant can permit entry of microorganisms leading to invasive infection.
      Topical emollients might improve skin integrity and barrier function and thereby
      prevent invasive infection, a major cause of mortality and morbidity in these
      infants. The aim of this study was to appraise and synthesise the evidence for
      topical application of emollients in the prevention of invasive infection and
      mortality in preterm infants. METHODS: We conducted a systematic review of
      randomised controlled trials that assessed the effect of prophylactic application
      of topical emollient (ointments, creams, or oils) on the incidence of invasive
      infection, and other morbidity and mortality in preterm infants. We used the
      standard methods of the Cochrane Neonatal Group to identify and appraise trials
      and extract and synthesise data. We prespecified subgroup analyses of trials in
      low-income and middle-income versus high-income countries. FINDINGS: We included
      16 trials (2809 infants). Methodological quality varied, with uncertainty about
      adequate allocation concealment methods in eight trials and lack of masking in
      all of the trials. Most trials in high-income countries compared expensive
      proprietary ointments or creams with standard care. Meta-analysis showed a
      significantly higher incidence of infection in infants treated with emollient
      (relative risk 1.20, 95% CI 1.01-1.42), but no significant effect on mortality or
      other morbidity. In low-income or middle-income countries, most trials compared
      low-cost natural plant oils with standard care, and meta-analyses did not show a
      significant effect on infection or mortality. Topical oil application increased
      rates of weight gain (~2 g/kg per day) and gain in length (~1 mm/kg per week).
      INTERPRETATION: The available trial data do not provide strong evidence that
      emollients prevent invasive infection or death in preterm infants. Given the
      burden of infectious morbidity and mortality in preterm infants in low-income or
      middle-income countries, further large, pragmatic trials of topical oils (which
      are low-cost, readily available, and widely accepted traditional neonatal skin
      care practices) are justified to improve the precision of the estimates of effect
      size. FUNDING: National Institute for Health Research.

PMID- 26312854
TI  - One size does not fit all. Management of the laparoscopic adjustable gastric band
      in pregnancy: a national prospective cohort study.
AB  - BACKGROUND: Pregnancies are increasingly seen in women with a gastric band, but
      no guidance exists on band management during pregnancy. Although band inflation
      can prevent excessive gestational weight gain and its associated complications,
      it might have detrimental effects on fetal growth. We compared maternal and
      perinatal outcomes according to band management strategy-keeping the band
      inflated throughout pregnancy versus deflation. METHODS: Data were collected by
      means of the UK Obstetric Surveillance System (UKOSS) on all pregnancies in women
      with a laparoscopic adjustable gastric band, booking in UK maternity units (Nov
      1, 2011, to Oct 31, 2012). Maternal and perinatal outcomes were compared
      according to band management strategy, with women in a control group who had not
      undergone the procedure and with national data. Multivariable regression analyses
      were used to adjust for potential confounders. FINDINGS: 109 cases were reported
      (prevalence 1.7 per 10 000 maternities), of whom 42 underwent band deflation and
      54 had inflation maintained (remainder unknown). Mean weight gain was higher with
      deflation than inflation (15.4 kg [95% CI 10.8-20.0] vs 7.6 [3.7-11.5], p=0.047).
      Some evidence of a higher risk of gestational hypertension with deflation than
      with inflation was noted (relative risk [RR] 6.86, p=0.07). There was strong
      evidence of a high risk of gestational hypertension with deflation compared with
      controls and national data (RR 4.74, p=0.001). Mean birth weight was
      significantly lower in the inflation group than in the deflation group (3380 g
      [95% CI 3255-3505] vs 3712 [3572-3851], p=0.002). Infants of women with deflation
      had a high risk of macrosomia compared with controls (adjusted RR 0.40, p=0.002)
      and national data (RR 2.04, p=0.01). INTERPRETATION: Pregnant women with a
      laparoscopic adjustable gastric band are high risk; the monitoring of both fetal
      and maternal wellbeing is essential. Maintainance of band inflation during
      pregnancy reduces gestational weight gain and associated complications, but
      affects fetal growth. Therefore, maintainance of band inflation throughout
      pregnancy cannot be recommended. However, inflation for part of the pregnancy
      might improve some maternal outcomes. Further studies are needed to define the
      optimum timing of band adjustment. FUNDING: Bristol Bariatric Pregnancy Research
      Hub.

PMID- 26312855
TI  - Epidemiology and outcomes of older patients admitted to Scottish intensive care
      units: a national database linkage study.
AB  - BACKGROUND: As the general population ages and life expectancy increases, health
      care use by elderly people increases, including intensive care. Rationing and
      variation of access are ethically and politically challenging. We aimed to
      characterise the population-based incidence of intensive care unit (ICU)
      admissions of elderly people in Scotland; compare ICU admission and mortality
      between elderly and younger populations; and compare treatment intensity between
      these groups. METHODS: We extracted complete, national 6-year cohort Scottish ICU
      admissions (Jan 1, 2005, to Dec 31, 2010) from the Scottish Intensive Care
      Society Audit Group database, which we linked to hospital Scottish Morbidity
      Record (SMR01) and death records. Annual incidence of ICU admissions of people
      aged 80 years or older was standardised for sex and socioeconomic status to the
      standard Scottish population (>=80 years) 2005-10. We compared mortality of
      elderly and younger people (<65 years) using the log-rank test. FINDINGS: During
      2005-10, 47 779 people were admitted to ICU (4561 patients >=80 years [9.5%,
      35.0/10 000 population], 26 784 patients <65 years [56.1%, 13.2/10 000]).
      Incidence of ICU admissions of elderly people fell from 36.6/10 000 population
      (95%CI 34.0-39.2) in 2005 to 30.3/10 000 (28.0-32.5) in 2010. ICU mortality was
      higher in elderly than in younger people (26.4% vs 16.1%, p<0.0001) as was 6-year
      mortality (68.0% vs 34.5%, p<0.0001). 2110 (80%) of 2627 elderly survivors were
      discharged home (younger 92%, 19 221/20 902), with a further 373 (14.2%) given
      rehabilitation (younger 1063, 5.1%) (chi(2)=525, p<0.0001). Age was an
      independent predictor of mortality (odds ratio 1.46, 95% CI 1.23-1.73, p<0.0001)
      after adjustment for confounders. In the pneumonia subgroup (elderly 294, younger
      2167), mean acute physiology scores were similar (17.0 [SD 6.4] vs 17.6 [6.6]),
      organ support was higher in the elderly patients (77.0% vs 68.1%, p<0.0001), and
      median ICU length of stay was lower (6 days [IQR 3-13] vs 8 [3-16], p<0.0001).
      INTERPRETATION: This study has shown that, by contrast with previously published
      research, admission rates of elderly people in Scotland fell between 2005 and
      2010. Only the fittest elderly individuals were admitted to ICU, where initially
      they received a higher intensity of treatment than did younger patients; however,
      duration of ICU stay was shorter. Mortality rates were high, and age was an
      independent predictor of mortality. FUNDING: Funding assistance for AD's MPH from
      Scottish Intensive Care Society, Scottish Society of Anaesthetists, Edinburgh
      Anaesthetics Research and Education Fund.

PMID- 26312856
TI  - Presurgical entorhinal cortex volume and postoperative seizure outcome in
      temporal lobe epilepsy.
AB  - BACKGROUND: Although temporal lobe surgery is an effective treatment for patients
      with intractable mesial temporal lobe epilepsy (mTLE), a third of patients will
      continue to experience seizures at 2 years after surgery. The reasons are
      unknown. One suggestion is that patients with abnormalities of the entorhinal
      cortex might have a subtype of mTLE that is resistant to surgery. We investigated
      the association between presurgical entorhinal cortex volume and postoperative
      outcome in patients with mTLE. METHODS: 78 patients with intractable mTLE and
      unilateral hippocampal sclerosis underwent comprehensive presurgical evaluation
      at the Department of Epileptology, University Hospital Bonn, Germany. Patients
      and 76 age-matched healthy controls received an MP-RAGE T1-weighted MRI. We
      determined left and right entorhinal cortex volume, masked to participant
      identity, using rigorous manual techniques. All patients had complex partial
      seizures, underwent amygdalohippocampectomy, and received postoperative outcome
      assessment. FINDINGS: There was a significant effect of group (controls, left
      mTLE, right mTLE) on the volume of the left (univariate ANOVA F=29.6, p<0.001)
      and right (F=8.3, p<0.001) entorhinal cortex, and entorhinal asymmetry (F=92.6,
      p<0.001). Post-hoc analysis with Bonferroni correction revealed that patients
      with left (p<0.001) and right (p=0.01) mTLE had significantly reduced volume of
      the ipsilateral entorhinal cortex relative to controls, and patients with right
      mTLE also had volume reduction of the contralateral entorhinal cortex (p=0.01).
      We found no significant differences in entorhinal cortex volumes and clinical
      data between patients (n=48, 62%) surgically rendered seizure free (ILAE I-II)
      and patients (n=30, 38%) with persistent seizures (ILAE III-VI). INTERPRETATION:
      These data indicate that gross atrophy of the entorhinal cortex is not a
      predictor of postoperative outcome in patients with intractable mTLE. We are
      evaluating whether alterations in entorhinal cortex connectivity and extent of
      resection are related to postoperative outcome in our series of patients.
      FUNDING: This work was supported by a UK Medical Research Council grant awarded
      to SSK.

PMID- 26312857
TI  - Effect of tissue inhibitor of metalloproteinases 3 on DLK1 shedding in cultured
      human pre-adipocytes and implications for adipose tissue remodelling.
AB  - BACKGROUND: Metabolically unhealthy obesity is associated with adipose tissue
      inflammation and increased risk of type 2 diabetes. Dysfunctional adipose tissue
      remodelling has been implicated in development of metabolically unhealthy
      obesity, but the pathogenesis remains poorly characterised. We hypothesised that
      in health, tissue inhibitor of metalloproteinases 3 (TIMP3) modulates adipose
      tissue remodelling by regulating extracellular matrix turnover and shedding of
      the adipogenic regulator DLK1, but that in adipose tissue inflammation it might
      drive development of metabolically unhealthy obesity. METHODS: Primary pre
      adipocyte and in-vitro-differentiated adipocyte cultures were established from
      abdominal subcutaneous adipose tissue donated by healthy women undergoing breast
      reconstruction. Cells were seeded onto collagen I, and subsequently treated with
      differentiation medium or tumour necrosis factor (TNF) alpha (50 ng/mL).
      Adenoviral transduction allowed TIMP3 overexpression. Media and lysates were
      collected for quantitative RT-PCR, and immunoblot and hydroxyproline release
      assays. Statistical analysis was performed with t testing or ANOVA. FINDINGS:
      Induction of differentiation in human pre-adipocytes reduced TIMP3 mRNA levels by
      75% (n=3, p<0.0001). Hydroxyproline release by differentiating pre-adipocytes was
      2.3 times greater than that by control-treated cells (mean 5.66 MUg/mL [SD 0.77]
      vs 2.45 [0.36], p<0.0001) indicating greater collagen I degradation. TNF alpha
      reduced TIMP3 mRNA levels by 66% in in-vitro-differentiated adipocytes (n=3,
      p<0.0001); reduced TIMP3 expression was confirmed by western blot. Shedding of
      soluble DLK1 (sDLK1) by pre-adipocytes was increased by TNF alpha and by
      overexpression of adenovirally delivered TIMP3 compared with control conditions,
      as confirmed by immunoblot (n=3). Addition of recombinant human sDLK1 (500 pM) to
      pre-adipocyte cultures reduced adipogenesis, as assessed by oil red O staining
      (n=2). INTERPRETATION: We have shown that TIMP3 is downregulated in adipogenesis,
      and by inflammatory signals in adipocytes. Furthermore, TIMP3 modulates sDLK1
      shedding and collagen I degradation. TIMP3 is known to inhibit ADAM17 (DLK1
      sheddase) and MMP14 (implicated in extracellular matrix turnover). TIMP3 might
      therefore integrate inflammatory signals with adipose remodelling. Subversion of
      remodelling pathways by chronic adipose inflammation might lead to maladaptive
      adipose expansion and metabolically unhealthy obesity. FUNDING: British Heart
      Foundation, Diabetes Research and Wellness Foundation Open Funding 2011.

PMID- 26312858
TI  - The role of metalloproteinases and their tissue inhibitors in adipose tissue
      remodelling and whole-body lipid distribution: a cross-sectional clinical study.
AB  - BACKGROUND: Metabolically unhealthy obesity is associated with insulin
      resistance. Dysfunctional adipose tissue remodelling might explain features of
      this disorder, such as chronic white adipose tissue inflammation, adipocyte
      hypertrophy, and ectopic lipid deposition. Metalloproteinases and their tissue
      inhibitors (TIMPs) have been implicated in human adipose tissue remodelling. In a
      cross-sectional study, we investigated the association of adipose
      metalloproteinase and TIMP expression with whole-body lipid distribution and
      insulin resistance. METHODS: Healthy women undergoing elective surgery donated
      fasting blood samples (for calculation of homoeostasis model assessment of
      insulin resistance [HOMA2-IR], the primary outcome). At operation 2 cm(3) biopsy
      samples of subcutaneous and visceral adipose tissue were obtained. 1 cm(3) was
      fixed, paraffin-embedded, and stained for adipocyte size quantification, and RNA
      was extracted from the remaining tissue for quantitative RT-PCR analysis. The
      women also underwent whole-body MRI for analysis of fat distribution. FINDINGS:
      26 women were recruited (mean age 50.3 years, SD 13.1) into five body-mass index
      categories (18.5-24.9 kg/m(2) [n=12, 46.1%], 25-29.9 [n=6, 23.1%], 30-34.9 [n=3,
      11.5%], 35-39.9 [n=3, 11.5%], >40 [n=2, 7.8%]). Mean fasting glucose was 5.29
      mmol/L (SD 0.66), mean fasting insulin 71.29 pmol/L (47.72), and mean HOMA2-IR
      1.35 (0.91). HOMA2-IR correlated with body-mass index (r=0.73, p<0.0001),
      subcutaneous and visceral adipose tissue volumes (r=0.94 and r=0.87,
      respectively; both p<0.0001), and hepatic fat fraction (r=0.57, p=0.013).
      Visceral adipose tissue MMP14 expression correlated strongly with hepatic fat
      fraction (r=0.944, p<0.0001), HOMA2-IR (r=0.74, p=0.01), and visceral adipose
      tissue volume (r=0.74, p=0.036). Subcutaneous adipose tissue TIMP3 expression
      correlated with subcutaneous adipocyte area (r=0.72, p=0.029), but not with HOMA2
      IR (r=-0.53, p=0.062). INTERPRETATION: The results suggest that
      metalloproteinases and TIMPs regulate adipose tissue remodelling and
      distribution. MMP14 has been implicated in collagen turnover in pre-adipocyte
      differentiation, whereas TIMP3 may modulate the shedding of DLK1, a regulator of
      adipogenesis. In our concurrent in-vitro study, we have shown that human
      adipocytes express metalloproteinases and TIMPs, and that their expression varies
      with inflammatory stimulation. These proteins might therefore integrate
      inflammatory signals with dysregulated adipose remodelling in metabolically
      unhealthy obesity. FUNDING: British Heart Foundation, Diabetes Research &
      Wellness Foundation Open Funding 2011.

PMID- 26312859
TI  - Integrated molecular analysis to investigate the role of microRNAs in pancreatic
      tumour growth and progression.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs involved in the post
      transcriptional regulation of mRNAs and are aberrantly expressed in cancer with
      important roles in tumorigenesis. A broad analysis of the combined effects of
      altered activities of miRNAs in pancreatic ductal adenocarcinoma (PDAC) has not
      been done, and how miRNAs might affect tumour progression or patient outcomes is
      unclear. METHODS: We combined data from miRNA and mRNA expression profiles from
      PDAC and normal pancreas samples (each n=9) and used bioinformatic analyses to
      identify a miRNA-mRNA regulatory network in PDAC. We validated our findings in
      PDAC cell-lines (PANC-1, MIA PaCa-2, LPc006, and LPc167), subcutaneous PDAC
      xenografts in mice, and laser capture microdissected PDACs from patients (n=91).
      We used this information to identify miRNAs that contributed most to
      tumorigenesis. FINDINGS: We identified three miRNAs (miR-21, miR-23a, and miR
      27a) that acted as cooperative repressors of a network of tumour suppressor genes
      that included PDCD4, BTG2, and NEDD4L. Inhibition of miR-21, miR-23a, and miR-27a
      had synergistic effects in reducing proliferation of PDAC cells in culture and
      the growth of xenograft tumours. The level of inhibition was greater than that of
      silencing oncomiR-21 alone. In PDACs from patients, high levels of the
      combination of miR-21, miR-23a, and miR-27a was a strong independent predictor of
      short overall survival after surgical resection (hazard ratio 3.21, 95% CI 1.78
      5.78). High expression of this combination was also associated with a more
      aggressive tumour phenotype: more microscopic tumour infiltration at resection
      margin and increased perineural invasion. INTERPRETATION: In an integrated data
      analysis, we identified functional miRNA-mRNA interactions that contribute to
      PDAC growth. These findings indicate that miRNAs act together to promote tumour
      progression and that future therapeutic strategies might require inhibition of
      several miRNAs. Furthermore, high tumour expression of the miR-21, miR-23a, and
      miR-27a combination could have potential use in the future as a prognostic
      signature for patients with PDAC. FUNDING: Peel Medical Research Trust, Alliance
      Family Foundation, Action Against Cancer, National Institute for Health Research,
      Association for International Cancer Research, Jason Boas Fellowship, Imperial
      Biomedical Research Centre, Rosetrees Trust, Joseph Ettedgui Charitable
      Foundation.

PMID- 26312860
TI  - Choice of a patient-reported outcome measure for patients with anal cancer for
      use in cancer clinical trials and routine clinical practice: a mixed methods
      approach.
AB  - BACKGROUND: In the USA, more than 7200 new cases of anal cancer were diagnosed in
      2014 with incidence rising. Concurrent chemoradiotherapy improves cancer-related
      outcomes but has led to an increase in acute and late adverse events. Patient
      reported outcomes (PRO) are increasingly included in trials as a surrogate
      measure for reporting of late adverse events. This study aimed to select the most
      effective PRO to use in clinical research and practice for anal cancer since no
      questionnaire specific for anal cancer has been developed. METHODS: A mixed
      methods approached was used. A systematic review estimated the frequency of use
      of PROs and clinician reporting instruments used in anal cancer trials including
      radiation treatment. Health professional semi-structured interviews explored
      preferred questionnaires and revealed missing items; analysis was done using the
      framework approach. Two symptom-based, validated questionnaires were selected and
      assessed by means of inductive content analysis to highlight discrepancies
      relevant to anal cancer. FINDINGS: 34 relevant studies reported on radiotherapy
      adverse events. For PROs, EORTC QLQ-C30 (n=5) and EORTC QLQ-CR38 (n=3) were used
      most frequently. RTOG/EORTC (n=17) and CTCAE (n=15) criteria were most commonly
      used for clinician reporting. EORTC QLQ-C30 and EORTC QLQ-CR38, and National
      Cancer Institute's (NCI) PRO-CTCAE were selected for further analysis. No
      consensus for questionnaire content or design was found through health
      professional interviews (n=8). Domains and codes relevant to anal cancer
      treatment were selected from interviews to inform questionnaire analysis. 27
      domains and 60 codes were found in EORTC questionnaires, and 21 domains and 44
      codes in NCI PRO-CTCAE. Four domains and 16 codes were not covered by EORTC
      systems including radiation skin reaction. Six domains and 45 codes were not
      covered by NCI PRO-CTCAE including vaginal stenosis and bowel urgency.
      INTERPRETATION: This study shows that there are gaps in the questionnaires
      commonly used to record adverse events using PROs for anal cancer. Expert opinion
      is valuable in highlighting relevant missing items but provides no consensus on
      design and wording preferences. For use in longitudinal follow-up of patients
      with anal cancer treated with (chemo)radiation, the EORTC-QLQ system has the
      fewest missing symptom items for use as a validated PRO in clinical research and
      practice. FUNDING: This abstract presents independent research funded by the
      National Institute for Health Research (NIHR).

PMID- 26312861
TI  - Use of a novel floxed mouse to characterise the cellular source of plasma
      coagulation FXIII-A.
AB  - BACKGROUND: Coagulation factor XIII-A has a crucial role in thrombus
      stabilisation and tissue repair. Factor XIII-A deficiency causes a severe
      bleeding phenotype and impaired wound healing, but the cellular origin of Factor
      XIII-A is unknown. To identify the cells that maintain the plasma pool, we
      generated a mouse floxed in coding exon7 of the factor XIII-A gene (F13A1). These
      mice were crossed with mice transgenic for Pf4-Cre-recombinase (thrombopoietic
      deletion) or Cd11b-Cre-recombinase (myeloid deletion). The resultant mice were
      compared with a Mpl-/- (thrombopoietin receptor knockout) thrombocytopenic murine
      model. METHODS: Factor XIII-A recombination was evaluated by quantitative PCR
      assay of genomic DNA from liver and spleen. Factor XIII-A enzyme activity was
      measured in plasma and platelets with a biotin incorporation assay. quantitative
      PCR was performed to determine factor XIII-A mRNA levels in aortic and cardiac
      tissue. Factor XIII-A transcripts were assayed in human umbilical blood
      haemopoietic cell lineages. FINDINGS: Selectivity of Pf4-Cre and Cd11b-Cre
      mediated deletion was confirmed in liver and spleen. A 40% decrease in factor
      XIII-A plasma activity was observed in Cd11b mice, whereas plasma activity was
      decreased by 85% and absent in platelets from Pf4 mice. By contrast, plasma
      factor XIII-A was normal in Mpl mice. Cd11b mice showed no reduction in factor
      XIII-A mRNA in cardiac tissue and a 54.6% reduction in aorta. A major decrease in
      factor XIII-A mRNA was observed in the aorta (91.6%) and heart (99.2%) of Pf4
      mice, but there was no change in expression in either tissue from Mpl mice. In a
      human stem-cell study, factor XIII-A mRNA transcription increased as common
      myeloid progenitors committed to become granulocyte-macrophage progenitors and as
      megakaryocyte-erythroid progenitors differentiated to both megakaryocytes and
      erythroblasts. INTERPRETATION: These results raise the possibility that a unique
      Pf4-dependent, Mpl-independent progenitor cell is the major source of the plasma
      pool. These findings might have implications for the management of factor XIII-A
      deficiency states. FUNDING: British Heart Foundation.

PMID- 26312862
TI  - Delay to admission to critical care and mortality among deteriorating ward
      patients in UK hospitals: a multicentre, prospective, observational cohort study.
AB  - BACKGROUND: Annually, more than 11 million patients are admitted to hospital
      overnight in England, but the UK is ranked 24 of 31 European countries with
      respect to per head provision of intensive care unit (ICU) beds. This lack of
      beds places strain on the capacity to admit patients from the ward because of
      high ICU occupancy. Such delay can cause harm, but the effect of such harm is
      difficult to measure. Prompt admissions are prompt precisely because these
      patients are severely unwell. Measured severity is unlikely to completely capture
      the clinical judgment used to allocate early admission, and therefore risk
      adjusted outcomes will be biased against the early admission. We aimed to
      evaluate the effect of delayed admission to critical care without this treatment
      selection bias. METHODS: We did a prospective cohort study of deteriorating ward
      patients assessed for critical care admission in National Health Service
      hospitals in the UK. Early admission was defined as within 4 h of assessment. The
      primary endpoint was 90-day survival. We used critical care occupancy as an
      instrumental variable, assuming that a full ICU could only affect outcome of a
      ward patient by deflecting or delaying admission. FINDINGS: 12 495 patients from
      48 hospitals were available for analysis of whom 3797 (30.4%) died within 90
      days. 4494 (36.0%) patients were admitted to critical care of whom 2492 (55.5%)
      were admitted early. The median time to admission was 2 h (IQR 1-3) with a
      bedside decision to admit, and 12 h otherwise (5-29). 991 patients (7.9%) were
      assessed when the critical care unit was fully occupied. Compared with those
      assessed when more than one bed was available, these patients were admitted less
      often (odds ratio [OR] 0.37, 95% CI 0.28-0.48), experienced greater delays
      (median increase 2 h, IQR 1-3), and deteriorated further while waiting (1.4
      ICNARC physiology points, 95% CI 0.4-2.5). Early admission reduced mortality (OR
      0.49, 95% CI 0.27-0.89). When averaged across the full population, absolute
      mortality fell by 13.9% (95% CI 25-23.0). INTERPRETATION: Our study has shown
      that the deteriorating ward patient is vulnerable with a high short-term
      mortality (none of these patients had treatment limitations). Delays to admission
      were large and common, and arose both from our inability to perfectly triage
      these patients, and from limits to the capacity of the system. That these delays
      cause harm is very likely. FUNDING: Wellcome Trust, National Institute for Health
      Research Service Support Costs, Intensive Care National Audit & Research Centre.

PMID- 26312863
TI  - Emergency department attendance by patients with cancer in the last month of
      life: a systematic review and meta-analysis.
AB  - BACKGROUND: Emergency department visits towards the end of life by people with
      cancer are increasing over time. This increase has occurred despite evidence of
      an association with poor patient outcomes, the majority of patients preferring
      home-based care, and significant overcrowding and capacity concerns for many
      emergency departments. We aimed to explore factors associated with emergency
      department attendance by cancer patients in the last month of life. METHODS: We
      searched Medline, Embase, CINAHL, PsychINFO, and the Cochrane Library from
      inception to February, 2014, for studies investigating emergency department
      attendances by adult cancer patients (>=18 years) towards the end of life. No
      time or language limitations were applied. We performed meta-analysis of factors
      using a random-effects model, with results expressed as odds ratios (OR) for
      emergency department attendance. Sensitivity analysis explored heterogeneity.
      FINDINGS: 30 studies were identified, reporting three demographic, five clinical,
      and 13 environmental factors; they included data from five countries and 1 181
      842 patients. An increased likelihood of emergency department attendance was
      found for men versus women (OR 1.24, 95% CI 1.19-1.29), black versus white race
      (1.45, 1.40-1.50), patients with lung cancer versus other cancers (1.17, 1.10
      1.23), and those of lowest versus highest socioeconomic status (1.15, 1.10-1.19).
      Patients receiving palliative care were less likely than those not receiving
      palliative care to attend the emergency department in the last month of life (OR
      0.43, 95% CI 0.36-0.51). INTERPRETATION: We have identified demographic (men,
      black race), clinical (lung cancer), and environmental (low socioeconomic status,
      no palliative care) factors associated with an increased risk of emergency
      department attendance. These findings could be used to develop screening
      interventions and assist policy makers in directing limited resources. Future
      studies should also investigate previously neglected areas of research, including
      psychosocial factors, and the emergency care preferences of patients and
      caregivers. FUNDING: LH is a PhD clinical training fellow and funded through
      project BuildCARE which is supported by Cicely Saunders International and The
      Atlantic Philanthropies, and led by King's College London, Cicely Saunders
      Institute of Palliative Care, Policy & Rehabilitation, UK.

PMID- 26312864
TI  - Multidimensional endotypes of asthma: topological data analysis of cross
      sectional clinical, pathological, and immunological data.
AB  - BACKGROUND: Incomplete understanding of mechanisms and clinicopathobiological
      heterogeneity in asthma hinders research progress. Pathogenic roles for T-helper
      type 17 (Th17) cells and invariant T cells implied by murine data have yet to be
      assessed in man. We aimed to investigate the role of Th17 and mucosal associated
      invariant T (MAIT) cells in airway inflammation; to characterise associations
      between diverse clinical and immunological features of asthma; and to identify
      novel multidimensional asthma endotypes. METHODS: In this single-centre, cross
      sectional observational study in the UK, we assessed volunteers with mild-to
      severe asthma and healthy non-atopic controls using clinical and physiological
      assessment and immunological sampling of blood, induced sputum, endobronchial
      biopsy, and bronchoalveolar lavage for flow cytometry and multiplex
      electrochemiluminescence assays. Primary outcomes were changes in frequencies of
      Th17 and MAIT cells between health and asthma using Mann-Whitney U tests and the
      Jonckheere-Terpstra test (linear trend across ranked groups). The study had 80%
      power to detect 60% differences in T-cell frequencies at p<0.05. Bayesian Network
      Analysis (BNA) was used to explore associations between parameters. Topological
      Data Analysis (TDA) was used to identify multidimensional endotypes. The study
      had local research ethics approval. All participants provided informed consent.
      FINDINGS: Participants were 84 male and female volunteers (60 with mild-to-severe
      asthma and 24 healthy, non-atopic controls) aged 18-70 years recruited from
      clinics and research cohorts. Th17 cells and gammadelta17 cells were not
      associated with asthma, even in severe neutrophilic forms. MAIT-cell frequencies
      were strikingly reduced in asthma compared with health (median frequency in blood
      0.9% of CD3+ cells [IQR 0.3-1.8] in asthma vs 1.6 [1.2-2.6] in health, p=0.005;
      in sputum 1.1 [0.7-2.0] vs 1.8 [1.6-2.3], p=0.002; and in biopsy samples 1.3 [0.7
      2.3] vs 3.9% [1.3-5.3%], p=0.02), especially in severe asthma where BAL
      regulatory T cells were also reduced compared with those in health (4.4, 3.1-6.1,
      vs 8.1, 5.6-10; p=0.02). BNA and TDA identified six novel clinicopathobiological
      clusters of underlying disease mechanisms, with elevated mast cell mediators
      tryptase (p<0.0001), chymase (p=0.02), and carboxypeptidase A3 (p=0.02) in severe
      asthma. INTERPRETATION: This study suggests that Th17 cells do not have a major
      pathogenic role in human asthma. We describe a novel deficiency of MAIT cells in
      severe asthma. We also provide proof of concept for application of TDA to
      identification of multidimensional clinicopathobiological endotypes. Endotypes
      will require validation in further cohorts. FUNDING: Wellcome Trust.

PMID- 26312865
TI  - What are important outcomes of bariatric surgery? An in-depth analysis to inform
      the development of a core outcome set and a comparison between the views of
      surgeons and other health professionals (the BARIACT study).
AB  - BACKGROUND: Outcome reporting in bariatric surgery needs uniformity. A core
      outcome set is an agreed minimum set of outcomes reported in all studies of a
      particular condition, but members of the bariatric multidisciplinary team might
      value outcomes differently. The aim of this study was to summarise existing
      outcome reporting in bariatric surgery, to inform the development of a core
      outcome set, and to compare outcomes selected as important by type of health
      professional. METHODS: Outcomes reported in randomised controlled trials (RCTs)
      and large non-randomised studies, identified by a systematic review, were listed
      verbatim. Frequency of outcome reporting and uniformity of definition were
      assessed. A questionnaire to rate the importance of each outcome was completed by
      members of the bariatric multidisciplinary team. Responses to each item were
      scored as 1 (not essential) to 9 (absolutely essential). We ranked outcomes
      according to percentage deemed important (7-9) and according to respondents by
      type of health professional. FINDINGS: We identified 1088 individual outcomes
      from 90 studies (39 RCTs), grouped them into health domains, and presented them
      as a questionnaire with 131 items to 489 multidisciplinary team members. Most
      outcomes (n=920, 85%) were reported only once. The largest outcome domain was
      surgical complications, and 432 outcomes (42%) corresponded to an adverse event.
      Only a quarter of outcomes (n=461) were defined, and were often contradictory.
      For questionnaire responders (n=164, response rate 33.5%), most were surgeons
      (n=80, 48.8%), followed by dietitians (n=31, 18.9%), nurses (n=24, 14.6%),
      physicians (n=12, 7.3%), and others (n=16, 9.9%). Improvement in diabetes was the
      top outcome for all health professionals. Seven of the surgeon's top ten outcomes
      were adverse events, compared with three for other health professionals. Groups
      valued a measure of weight differently (third vs 15th for other health
      professionals and surgeons, respectively). INTERPRETATION: This study shows that
      the assessment of bariatric surgery focuses largely on adverse events and
      resolution of comorbidity, but that reporting is inconsistent and ill-defined.
      Substantial variation between the views of surgeons and those of other health
      professionals was evident. The next step is to provide feedback to participants
      and to survey their views again before a final consensus meeting to produce a
      core outcome set for the Benefits and Adverse events in BARIAtric surgery
      Clinical Trials (BARIACT) as a solution to this problem. FUNDING: National
      Institute for Health Research (NIHR), and the NIHR Health Technology Assessment
      programme. This work was also undertaken with the support of the MRC ConDuCT-II
      Hub (Collaboration and innovation for Difficult and Complex randomised controlled
      Trials In Invasive procedures, MR/K025643/1).

PMID- 26312866
TI  - Association of anti-carbamylated protein antibodies with long-term disability and
      increased disease activity in patients with early inflammatory arthritis: results
      from the Norfolk Arthritis Register.
AB  - BACKGROUND: Anti-citrullinated protein antibodies (ACPA) predict increased
      disease activity and disability in patients with inflammatory arthritis such as
      rheumatoid arthritis. However, the absence of these antibodies does not confer
      universally good prognosis. Recently, a new set of antibodies, anti-carbamylated
      (anti-CarP) antibodies, have been identified in patients with rheumatoid
      arthritis. This study aimed to investigate the association between anti-CarP
      antibodies, disability, and disease activity in these patients. METHODS: Adults
      with two or more swollen joints for at least 4 weeks were recruited from the
      Norfolk Arthritis Register (NOAR). At baseline patients completed the health
      assessment questionnaire (HAQ). The Disease Activity Score in 28 joints (DAS28)
      was calculated and rheumatoid arthritis classification criteria applied. ACPA and
      anti-CarP antibodies were measured on stored serum samples obtained within the
      first year of the study. The HAQ was repeated after 1, 2, 3, 5, 7, 10, 12, 15,
      and 20 years, and DAS28 scores done every 5 years. Generalised estimating
      equations (GEE) tested the association between anti-CarP antibodies and
      longitudinal HAQ and DAS28 scores. FINDINGS: 1995 patients were included; 1310
      (66%) were women and median age at onset was 55 years (IQR 43-66). Anti-CarP
      antibodies were positive in 460 patients (23%), and 1221 (61%) met rheumatoid
      arthritis classification criteria. Median follow-up was 7 years (IQR 5-11).
      Patients who were anti-CarP antibody positive had significantly more disability
      over time and higher levels of disease activity than those who were negative
      (multivariate GEE adjusted for age, sex, smoking status, ACPA, and year of
      recruitment to NOAR: beta coefficient for HAQ 0.13, 95% CI 0.03-0.23, and for
      DAS28 0.31, 0.12-0.49). Statistically significant associations were also seen in
      a subanalysis of 1092 ACPA-negative patients (HAQ 0.15, 0.02-0.29; DAS28 0.37,
      0.11-0.63). In ACPA-positive and rheumatoid arthritis subgroups, anti-CarP
      antibodies were significantly associated with DAS28 (0.30 [0.02-0.57] and 0.21
      [0.04-0.37], respectively), and positive associations were also seen with HAQ
      scores, but these did not meet statistical significance. INTERPRETATION: In this
      study the presence of anti-CarPA was associated with increased burden of
      disability as measured by the HAQ and higher disease activity in patients with
      inflammatory arthritis. Since GEE models include outcome data at all timepoints,
      these associations are long term. Our results suggest that anti-CarP antibodies
      might provide additional prognostic information to ACPA and in particular
      identify ACPA-negative patients with poor prognosis. FUNDING: Arthritis Research
      UK.

PMID- 26312867
TI  - Natural killer cell maturation markers in the human liver and expansion of an
      NKG2C+KIR+ population.
AB  - BACKGROUND: Selected populations of murine natural killer (NK) cells possess
      memory features to haptens, cytokines, and viruses. Liver-specific adhesion
      molecules CXCR6 and CD49a have been identified as surface markers in mice. In
      people, expansion of long-lived terminally differentiated NKG2C+ populations
      occur in the blood after viral infection. We aimed to compare intrahepatic and
      blood NK cell receptor expression to determine the existence of CD49a+ and CXCR6+
      NK cells in human liver and define the maturation status of NKG2C+ NK cells at
      this site. METHODS: Tissue samples were taken from the liver margin of 39
      patients with hepatic metastases and flushed with chelating buffer followed by
      collagenase or mechanical digestion. Paired peripheral blood samples were taken
      from 15 patients, the remainder being unpaired. Mononuclear cells were isolated
      by ficoll separation and cell surface staining performed for CD3, CD56, CD16,
      CD57, CD117, CD161, CD158a, CD158b, CD49a, CD49b, CXCR6, NKG2C, and NKp46.
      Statistical analysis to compare intrahepatic and blood NK cell receptor
      expression included the median, IQR, and Mann-Whitney U test. FINDINGS:
      Frequencies of NK cell precursors were similar in the liver and the blood (0.91%
      [0.62-3.26] vs 0.87 [0.41-1.52]); however, expression of all later markers of
      maturity were reduced including CD16 (47% [40.4-61.4] vs 88.7 [82.2-93.2],
      p<0.0001), CD57 (30.7% [25.0-53.9] vs 73.4 [70.4-87.6], p=0.0003), and KIR (11.2%
      [7.5-14.5] vs 26.7 [17.3-30.8], p<0.0001). Expanded hepatic CD16- NK cells were
      particularly immature with reduced CD57 and increased CD161 compared with the
      blood. NKG2C+ NK cells were found in similar frequencies in liver and blood. The
      hepatic NKG2C+ population was terminally differentiated, as in the circulation,
      but demonstrated a three-fold increase in KIR expression compared with NKG2C-
      counterparts, which was not seen in the blood. As in previously published
      research in mice, CD49a+ and CXCR6+ NK cells were liver resident (6.5% [3.9-14.6]
      liver vs 2.1 [1.3-4.3] blood, p<0.0001, and 65.3 [48.1-75.2] vs 4.5 [1.43-12.12],
      p=0.0039, respectively). Both populations were immature, with reduced KIR
      expression. INTERPRETATION: We have shown that the liver contains an expanded
      population of immature CD16- NK cells. These cells might traffic from the blood
      and then differentiate into hepatic-specific CD49a+ and CXCR6+ NK cells. The
      function of these subsets is unknown but their immaturity hints against memory.
      Terminally differentiated NKG2C+ cells show KIR expansion in the human liver and
      probably represent an antigen-experienced population, raising the question of
      whether the liver is a site of NK cell memory acquisition. FUNDING: MRC Clinical
      Research Fellowship.

PMID- 26312868
TI  - The active intrathecal B-cell response in LGI1-antibody encephalitis.
AB  - BACKGROUND: Leucine-rich glioma inactivated 1 (LGI1) is a component of the
      voltage-gated potassium channel complex. IgG antibodies against LGI1 are
      associated with immunotherapy-responsive encephalitis and epilepsies. LGI1
      antibody concentrations are 10-100 times greater in serum than in cerebrospinal
      fluid (CSF). Oligoclonal IgG bands are rarely found in patients with LGI1
      antibody encephalitis or epilepsy. These observations raise questions about the
      sources of the B cells that result in production of LGI1 antibodies and how the
      IgGs reach the brain. We aimed to investigate the migration and expansions of
      peripheral and central B cells to the production of LGI1-specific IgG. METHODS:
      We performed PCR amplification and next generation deep immune repertoire
      sequencing of immunoglobulin (Ig) heavy chain variable regions (VH) from CSF and
      subsorted peripheral blood B-cell populations from two patients with limbic
      encephalitis and faciobrachial dystonic seizures associated with LGI1 antibodies.
      Bioinformatics clustering of related IgM-VH or IgG-VH transcripts was used to
      determine whether active B-cell diversification could be observed, and whether
      intrathecal B-cell repertoires, if present, were related to peripheral B cells.
      FINDINGS: We identified clusters of related Ig-VH transcripts in the CSF of both
      patients. Within these clusters there was a range of somatic hypermutations along
      the IGHV germline segment-derived portion. In addition, we identified a large
      number of closely related Ig-VH clusters that were common to both CSF and
      peripheral blood, including a small number of dominating Ig-VH clusters that
      might represent the most active clonally related B-cell populations.
      INTERPRETATION: Our data suggest that some B-cell affinity maturation occurs
      inside the CNS compartment in LGI1-antibody encephalitis. Somatic hypermutation
      rates point to a CSF antigen-driven activation of clonally related B cells that
      shape the intrathecal immune repertoire. The target antigen or antigens of these
      clonally related B cells remain unknown; our work continues to determine the
      relative contribution of intrathecally activated and peripheral LGI1-specific B
      cells in this autoimmune CNS disease. FUNDING: Wellcome Trust Intermediate
      Fellowship to SRI, Fulbright-MS Society, Epilepsy Research UK, BMA Vera Down
      Research Grant.

PMID- 26312869
TI  - Is variation in copy number of the human beta defensin gene cluster associated
      with preterm birth?
AB  - BACKGROUND: Increased expression of antimicrobial peptides including human beta
      defensins (HBD) has been reported in the amniotic fluid and vaginal secretions of
      women who deliver preterm. We have previously shown that these women have
      increased first trimester serum HBD2. The gene encoding HBD2, DEFB4A, is part of
      a defensin beta (DEFB) cluster on chromosome 8 that is variable in copy number.
      Increased serum HBD2 is associated with increased DEFB copy number. We aimed to
      test the hypothesis that variation in DEFB copy number is associated with preterm
      birth. METHODS: In a retrospective, case-control study, genomic DNA and serum
      were extracted from blood collected from white European women at 11-13 weeks'
      gestation attending King's College Hospital between March 1, 2006, and Sept 30,
      2010. DEFB copy number was determined by paralogue ratio test. Serum HBD2
      concentration was measured by ELISA. Data were analysed with Pearson correlation
      (Excel, version 2010) and binary logistic regression (SPSS, version 20).
      FINDINGS: Cases were 102 women who either delivered preterm in the index
      pregnancy or had a history of preterm delivery. Controls were 152 women who had
      had at least one previous term delivery and delivered at term in the index
      pregnancy; they had no history of preterm birth. Modal copy number was 4 (range 2
      7). Serum was available from 140 women (30 cases, 54 controls, 56 not included in
      the genetic association study). Median HBD2 concentration was 761.5 pg/mL (IQR
      449.6-1232.0). There was no association between DEFB copy number and preterm
      birth, nor was there a correlation between copy number and serum HBD2
      concentration. INTERPRETATION: Although variation in HBD2 protein expression in
      the first trimester might be useful to predict risk of preterm birth, we found no
      association between DEFB copy number and preterm birth. Nor did we find a
      correlation between DEFB copy number and serum HBD2 expression in the first
      trimester of pregnancy; this might be due to variation in regulatory sequences
      some of which are progesterone and oestrogen sensitive-between individual copies.
      FUNDING: Wellcome Trust, Wellbeing of Women.

PMID- 26312870
TI  - Clinical utility of random anti-tumour necrosis factor drug testing and
      measurement of anti-drug antibodies on long-term treatment response in rheumatoid
      arthritis.
AB  - BACKGROUND: Up to 40% of patients with rheumatoid arthritis treated with anti
      tumour necrosis factor (TNF) drugs do not respond because of primary inefficacy
      or loss of response. Although one explanation is that immunogenicity leads to the
      development of anti-drug antibodies and low drug concentrations, the clinical
      usefulness of pharmacological monitoring is debated. Our aim was to assess
      whether the presence of anti-drug antibodies and non-trough drug concentrations
      could predict treatment response in patients with rheumatoid arthritis treated
      with anti-TNF drugs. METHODS: 331 patients were selected from a multicentre
      prospective cohort (160 treated with adalimumab, 171 etanercept). Serum samples
      were collected at 3, 6, and 12 months after treatment initiation. Anti-drug
      antibodies were measured with RIA, drug concentrations with ELISAs, and Disease
      Activity Score in 28 joints (DAS28) at each timepoint. Linear and logistic
      regression, generalised estimating equation (GEE), and receiver operating
      characteristic curves were used to test the association and predictive value of
      anti-drug antibodies and non-trough drug concentrations on treatment response
      (DeltaDAS28). FINDINGS: 835 serial samples were tested (414 adalimumab, 421
      etanercept). Anti-adalimumab antibodies were detected in 31 (24.8%) of 125
      patients who had completed 12 month follow-up and none of the etanercept
      patients. The presence of anti-drug antibodies was associated with lower
      adalimumab concentrations (Spearman r=-0.66, p=0.0041). At 3 months, anti-drug
      antibody formation and low adalimumab concentrations were significant predictors
      of poor treatment response at 12 months (area under curve [AUC] 0.68, 95% CI 0.54
      0.81, and 0.66, 0.55-0.77, respectively; and both combined 0.71, 0.57-0.85).
      Adalimumab concentration was the most significant independent predictor of
      DeltaDAS28 after adjustment for confounders (regression coefficient 0.12, 95% CI
      0.06-0.18; p=0.003). High etanercept concentrations were associated with better
      treatment response (p=0.01), but low concentrations at 3 months were not a
      significant predictor of poor treatment response at 12 months (AUC 0.58, 95% CI
      0.46-0.70). In the combined GEE model including adalimumab and etanercept, a body
      mass index of 30 kg/m(2) or more was associated with low drug concentrations
      (regression coefficient 0.78, 95% CI 0.37-1.18; p<0.0001). INTERPRETATION:
      Pharmacological testing in anti-TNF initiated patients is clinically useful even
      in the absence of trough levels. At 3 months, presence of anti-drug antibodies
      and low adalimumab concentrations are a significant predictor for poor treatment
      response at 12 months. Strengths of this study include a large, prospective
      cohort and use of RIA to measure antibodies (less prone to drug interference).
      Although non-trough concentrations might have underestimated the frequency of
      antibodies, their presence still predicted response. FUNDING: MJ is a MRC
      Clinical Training Fellow supported by the North West England Medical Research
      Council Fellowship Scheme in Clinical Pharmacology and Therapeutics, which is
      funded by the UK Medical Research Council (grant number G1000417/94909), ICON,
      GlaxoSmithKline, AstraZeneca, and the Medical Evaluation Unit. Arthritis Research
      UK (grant ref 20385).

PMID- 26312871
TI  - Molecular mechanisms of myocardial nitroso-redox imbalance during on-pump cardiac
      surgery.
AB  - BACKGROUND: The mechanism responsible for left ventricular dysfunction after
      cardiac surgery is only partly understood. In isolated rat hearts subjected to an
      ischaemia-reperfusion protocol, left ventricular dysfunction was associated with
      uncoupling of endothelial nitric oxide synthase (NOS) activity secondary to
      oxidation of the NOS cofactor, tetrahydrobiopterin (BH4). Here we investigated
      the effect of cardiopulmonary bypass and reperfusion on myocardial nitroso-redox
      balance in patients undergoing cardiac surgery. METHODS: From 116 patients who
      underwent elective cardiac surgery on cardiopulmonary bypass, paired samples of
      the right atrial appendages were obtained before venous cannulation of the right
      atrium and after myocardial reperfusion. Superoxide production from atrial
      samples was measured by lucigenin (5 MUmol/L) enhanced chemiluminescence and 2
      hydroxyethidium (2-OHE) detection by high-performance liquid chromatography
      (HPLC). BH4, oxidised biopterins, GTP-cyclohydrolase 1 (GTPCH-1, the rate
      limiting enzyme in BH4 synthesis), and NOS activity ((14)C L-arginine to L
      citrulline conversion) were measured by HPLC. FINDINGS: Atrial superoxide
      production increased significantly after reperfusion (from mean 37.83 relative
      light units per s per mg [SE 3.71] before cannulation to 65.02 [6.01] after
      reperfusion, p<0.0001; n=46 samples from 23 patients) due to increased
      mitochondrial and NOX2 oxidase activity (by 309% and 149%; p=0.002 and p=0.0002,
      respectively) and uncoupling of NOS activity. Atrial content of BH4 after
      perfusion was reduced (by 32%, p=0.001), as was activity of GTPCH1 (50%,
      p<0.0001). NOS activity decreased significantly after reperfusion (60%, p=0.0005)
      and this reduction was not affected by BH4 supplementation (10 MUM) or NOX2
      inhibition ex vivo. Instead, we identified increased endothelial NOS s
      glutathionylation as the main mechanism for NOS uncoupling after reperfusion.
      Reversing NOS s-glutathionylation with dithiothreitol (100 MUmol/L) completely
      restored NOS activity after reperfusion (p=0.34). INTERPRETATION: Our findings
      suggest that NOS s-glutathionylation, rather than BH4 depletion, accounts for NOS
      dysfunction in patients after cardiac surgery and cardiopulmonary bypass.
      FUNDING: British Heart Foundation.

PMID- 26312872
TI  - A role for helminth parasites in achieving immunological tolerance in
      transplantation.
AB  - BACKGROUND: Helminths infect more than a quarter of the world's population. Their
      success as parasites is the result of active immunomodulation of the host immune
      response, which can have benefits for the host, particularly in suppressing
      harmful allergic and autoimmune responses. Accordingly, we tested the hypothesis
      that helminth infection reduces the immune response to allograft transplantation.
      METHODS: C57BL/6 mice were implanted with a subcutaneous minipump that delivered
      a continuous infusion of secreted products from the model mouse intestinal
      parasite, Heligmosomoides polygyrus (equivalent to 7 MUg of protein per day).
      Simultaneously, fully allogeneic skin grafts from BALB/c donors were performed. 7
      days later, lymphocytes were isolated from allograft draining lymph nodes and
      analysed by flow cytometry. FINDINGS: Flow cytometric analysis showed a 41.7%
      increase in the mean percentage of CD4+CD25+Foxp3+ regulatory T cells (of total
      CD4 cells) from a baseline of 8.1% (95% CI 7.4-8.8) in untreated mice to 11.5%
      (8.8-14.2) in the treatment group (p=0.0085). Treatment with parasite products
      also increased mean expression of the regulatory cell surface receptor PD1 by
      62.2% in the effector CD4 T-cell population from a baseline of 7.7% (5.7-9.6) to
      12.5% (7.5-17.4) (p=0.03). INTERPRETATION: The results show that helminth-derived
      products can powerfully induce regulatory immunological mechanisms in the
      presence of a fully allogeneic transplant. Identification of the specific
      mechanisms involved in suppression of allograft rejection by helminth parasites
      could lead towards development of safe and effective novel therapeutic
      strategies. FUNDING: Wellcome Trust.

PMID- 26312873
TI  - Neural respiratory drive and symptoms that limit exercise in chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Exercise capacity in chronic obstructive pulmonary disease (COPD) is
      limited by both breathlessness and leg muscle fatigue. Neural respiratory drive,
      measured as diaphragm electromyogram (EMGdi) activity expressed as a proportion
      of maximum (EMGdi%max), quantifies the mechanical load on the respiratory muscles
      and relates closely to breathlessness. We tested the hypothesis that end-exercise
      EMGdi%max would be higher in patients stopping because of breathlessness than in
      those limited by leg fatigue. METHODS: EMGdi, ventilation, rate of oxygen
      consumption (VO2), and ventilatory reserve (ventilation/maximum ventilatory
      volume ratio [VE/MVV]) were measured continuously in patients with COPD during
      exhaustive cycle ergometry. EMGdi was measured with a multipair oesophageal
      catheter passed per-nasally. Differences in physiological variables between
      groups of patients stopping because of breathlessness, leg fatigue, or both were
      assessed with one-way ANOVA. FINDINGS: 23 patients were included (median FEV1,
      39% of predicted, IQR 30.0-56.8). End-exercise EMGdi%max was significantly higher
      in patients stopping exercise because of breathlessness (n=12, median EMGdi%max
      75.7% [IQR 69.5-77.1]) than in those stopping because of leg fatigue (n=8, 44.1
      [39.4-63.3]) or both (n=3, 74.1 [63.6-81.2]) (p=0.02). There were no significant
      differences between the groups in end-exercise ventilation (breathlessness 25.7
      L/min [16.3-32.0] vs leg fatigue 31.5 [20.9-39.6] vs both 22.0 [17.7-35.7]), VO2,
      (13.4 mL/min per kg [11.6-14.2] vs 12.1 [10.4-14.8] vs 9.4 [9.1-12.4]), or VE/MVV
      (80.4% [72.6-88.3] vs 57.8 [52.1-92.6] vs 63.9 [34.5-88.9]). INTERPRETATION:
      These results suggest that patients limited by breathlessness due to ventilatory
      constraints can be identified as those reaching near-maximum levels of neural
      respiratory drive during exercise. Measurement of EMGdi%max during exercise could
      prove useful in identifying patients whose functional performance would be best
      optimised by improvment in pulmonary mechanics rather than interventions to train
      peripheral muscle groups. FUNDING: None.

PMID- 26312874
TI  - Regulation of neutrophilic inflammation in lung injury induced by community
      acquired pneumonia.
AB  - BACKGROUND: Community-acquired pneumonia is commonly caused by Streptococcus
      pneumoniae, which is associated with excessive neutrophilic inflammation. The
      high-affinity thrombin receptor, proteinase-activated receptor 1 (PAR1), has been
      implicated in mediating the interplay between coagulation and inflammation.
      However, its role during S pneumoniae-induced neutrophilic inflammation, and the
      mechanisms for neutrophil recruitment in this context are poorly understood. We
      aimed to investigate the role of neutrophilic inflammation and PAR1 in S
      pneumoniae-induced pneumonia. METHODS: We used the most clinically advanced PAR-1
      antagonist, SCH530348, and performed neutrophil depletion and chemokine
      neutralisation studies in two murine models. We also did translational studies to
      examine CXC and CC chemokine receptor expression by flow cytometry on neutrophils
      in blood and bronchoalveolar lavage fluid (BALF) from mechanically ventilated
      patients with acute respiratory distress syndrome induced by community-acquired
      pneumonia. FINDINGS: S pneumoniae infection led to activation of coagulation,
      increased neutrophil recruitment, and increased PAR-1 expression. By contrast
      with neutrophil depletion, PAR1 antagonist treatment significantly reduced
      neutrophil recruitment (mean difference 26.7 * 10(3) cells per mL [SE 4.9] at 4
      h, p=0.0002; and 149.3 [41.4] at 24 h, p=0.0032) without being detrimental to
      host defence. Markers of alveolar leak, coagulation activation, and
      proinflammatory cytokines and chemokines (interleukin 1beta, CXCL1, CCL2, and
      CCL7) were attenuated. Neutralisation studies demonstrated that interleukin 1beta
      and CCL7, but not CXCL1 and CCL2, had a key role in neutrophil recruitment in
      this model. In patients with acute respiratory distress syndrome induced by
      community-acquired pneumonia (n=10), CXCR1 and CXCR2 expression on BALF
      neutrophils was higher than in controls (n=3) (median difference in mean
      fluorescence intensity [MFI] 703 arbitrary units [p=0.0699] for CXCR1 and 658.7
      [p=0.0280] for CXCR2). The expression of CXCR1 was decreased on neutrophils from
      BALF compared with blood (median difference in MFI 1337, p=0.0020) and that of
      CXCR2, CCR1, CCR2, and CCR3 was increased (125.5, p=0.0020; 335.1, p=0.0020; 116,
      p=0.0068; and 275, p=0.0020; respectively). INTERPRETATION: These findings
      suggest that clinically available PAR1 antagonists might offer a novel
      therapeutic approach for prevention and management of excessive neutrophilic
      inflammation and alveolar barrier dysfunction in pneumococcal pneumonia without
      compromising host defence. Furthermore, these data highlight a role for chemokine
      receptor switching in acute respiratory distress syndrome induced by community
      acquired pneumonia. FUNDING: Wellcome Trust.

PMID- 26312875
TI  - Potential for monocyte recruitment by IgE immunotherapy for cancer in a rat model
      of tumour metastasis.
AB  - BACKGROUND: Nearly all anti-tumour antibodies are of a single class-namely, IgG.
      Efficacy might be improved by development of tumour-specific IgE antibodies,
      which have higher affinities for effector cell receptors and perform potent
      immune functions. MOv18IgE, which targets folate receptor alpha (FRalpha), is a
      novel system to model this hypothesis. Human chimeric MOv18 IgE has shown
      superior efficacy in two murine xenograft models compared with MOv18 IgG1. Our
      aim was to examine the potential of this antibody class to activate monocytes.
      METHODS: We developed an immunocompetent rat model system of rat tumour lung
      metastases expressing human FRalpha, and engineered surrogate rat MOv18 IgE and
      IgG antibodies to assess their efficacy and ability to recruit monocytes in the
      rat model system. FINDINGS: In-vivo assessment of the efficacy of rat MOv18 IgE
      demonstrated superior tumour growth restriction compared with rat MOv18 IgG
      (tumour occupancy 6.8% [SE 1.6] vs 16.0 [1.7]; p<0.0001). We measured significant
      CD68-positive (CD68+) macrophage infiltration of tumours after MOv18 IgE
      treatment (mean ratio of CD68+ cells in tumour vs periphery 3.6 [0.5] for MOv18
      IgE-treated tumours vs 2.3 [0.3] for MOv18 IgG-treated tumours; p=0.03).
      INTERPRETATION: Our in-vivo studies using rat MOv18 IgE show the importance of
      monocyte recruitment in the efficacy of this antibody, and provide further
      evidence that tumour-specific IgE antibodies might offer improved efficacy
      against cancer by recruiting key immune effector cells. FUNDING: Academy of
      Medical Sciences Starter Grant, Cancer Research UK New Agents Committee Grant.

PMID- 26312876
TI  - Divergent transcriptional activation by glucocorticoids in mouse and human
      macrophages.
AB  - BACKGROUND: Innate immune cells are major targets of glucocorticoids as anti
      inflammatory therapies. Glucocorticoids are metabolic hormones that provide
      natural feedback regulation of immune function. They are widely prescribed, but
      use is restricted by side-effects. Much of our knowledge about how
      glucocorticoids work comes from studies in mice. However, since mice are
      imperfect models of human macrophage biology, for example in inflammation,
      whether this knowledge can be directly translated to man is uncertain. We aimed
      to address this uncertainty. METHODS: We performed global expression profiling of
      primary cultured mouse and human macrophages, sampling at six points during 24 h
      after treatment with glucocorticoids. To assess the mechanism behind the
      regulation of transcription we also determined the DNA-binding pattern of the
      nuclear glucocorticoid receptor (GR) using chromatin immunoprecipitation followed
      by sequencing (ChIP-seq). FINDINGS: Glucocorticoids initiated a temporal cascade
      of predominantly induced gene regulation in both species, but with little overlap
      in the gene sets. Single nucleotide polymorphisms (SNPs) linked to inflammatory
      disease were enriched near human (but not mouse) glucocorticoid-regulated genes.
      Using our genes as candidates, we identified eight SNPs reported as low
      significance that might be of biological relevance. We found that GR bound at
      candidate enhancers in the vicinity of induced genes and that this was strongly
      associated with canonical GR-dimer binding motifs. By contrast, promoters of
      induced genes, and the smaller set of repressed genes, showed no association with
      GR binding. Sites bound by GR were also not conserved between human and mouse
      macrophages, due to loss of the GR binding motif, which reflects the divergence
      in transcription. INTERPRETATION: We conclude that the response of innate immune
      cells to glucocorticoids has diverged significantly between species because of
      the gain or loss of glucocorticoid-responsive enhancers. FUNDING: Wellcome Trust.

PMID- 26312877
TI  - Genome-wide transcription profiling in neutrophils in acute respiratory distress
      syndrome.
AB  - BACKGROUND: Acute respiratory distress syndrome (ARDS) is characterised by
      diffuse neutrophil-mediated alveolar inflammation. Recently, we demonstrated that
      blood polymorphonuclear leucocytes (PMNs) in ARDS are basally activated, and
      exhibit aberrant oxidative burst and survival responses. The molecular mechanisms
      governing ARDS PMN function and longevity are incompletely understood. We aimed
      to use genome-wide transcriptional profiling of ARDS blood PMNs to explore
      underlying disease mechanisms and identify therapeutic targets aimed at
      manipulating PMN function and longevity. METHODS: GeneChip Affymetrix
      oligonucleotide arrays were used to assess global transcriptional profiles in
      highly pure PMNs from ventilated patients fulfilling the Berlin ARDS definition
      (n=10), in freshly isolated PMNs from age-matched and sex-matched healthy
      volunteers (n=10), and in healthy volunteer PMNs exposed in vitro to recombinant
      human granulocyte-macrophage colony stimulating factor (rhGM-CSF) (1 ng/mL for 6
      h). Ingenuity Pathway Analysis software was used to map probes identified as
      important onto specific pathways. FINDINGS: Transcriptomic analysis showed that
      1319 genes were altered in ARDS PMNs relative to healthy volunteer PMNs. Compared
      with well established reference databases, the gene expression profile in ARDS
      PMNs showed near-complete correlation to datasets derived from patients with
      sepsis and burns. Transcripts enriched in ARDS PMNs were differentially expressed
      in known functional network pathways associated with cancer, cellular compromise,
      apoptotic mechanisms, and chemotaxis. Of the observed gene changes, only 292
      (22%) were seen in healthy volunteer PMNs after exposure to rhGM-CSF, of which
      216 showed the same directional change as ARDS PMNs. INTERPRETATION: Existing
      genome-wide studies in ARDS use total blood leucocytes; our study is the first,
      to our knowledge, to use unbiased global genomic profiling of highly pure ARDS
      blood PMNs in parallel with age-matched and gender-matched healthy volunteer PMNs
      treated with rhGM-CSF. Collectively our results show that ARDS PMNs display
      important de-novo transcriptional activity. The global transcriptomic changes
      were consistent with the observed aberrant ARDS PMN survival and functional
      phenotype that we have previously reported, and show near-complete correlation to
      existing sepsis and burns datasets, but only limited transcriptomic overlap with
      healthy volunteer PMNs treated with rhGM-CSF. FUNDING: National Institute for
      Health Research, GlaxoSmithKline.

PMID- 26312878
TI  - Anti-cancer effects of oncolytic viral therapy combined with photodynamic therapy
      in human pancreatic cancer cell lines.
AB  - BACKGROUND: Oncolytic viral therapy and photodynamic therapy are potential
      therapies for inoperable or advanced pancreatic cancer. Our aim was to
      investigate the anti-cancer killing effects of reovirus therapy combined with
      protoporphyrin IX (PpIX)-mediated photodynamic therapy on a variety of human
      pancreatic cancer cell lines. METHODS: Pancreatic cancer cell lines (PsPC-1 and
      BXPC-3) and a non-cancer control cell line (HEK293) were infected with reovirus
      serotype 3 strain Dearing (T3D) at 0, 0.1, 1, and 10 plaque-forming units (PFU)
      per cell for 48 h. Cells were incubated with PpIX pro-drug 5-aminolevulinic acid
      (5-ALA) at 0, 1, 2, 3, and 4 mM for 4 h. Then, cells were photo-irradiated for 15
      min with visible red light-emitting diodes with a light-fluence of 0.54 J/cm(2)
      of 653 nm (PpIX optimal excitation wavelength). The killing effects of reovirus
      combined with PpIX-mediated photodynamic therapy were analysed in
      methylthiazoltetrazolium (MTT) and trypan blue assays. The effect of adding
      reovirus after photodynamic therapy was also assessed. The statistical
      significance of the difference between groups was assessed with the two-tailed
      Student's t test. p<0.05 was considered statistically significant. FINDINGS:
      Reovirus monotherapy induced cell death in the two pancreatic lines (mean 57% [SE
      10.2] at 10 PFU per cell). PpIX-mediated PDT monotherapy induced cell death in a
      dose-dependent manner (mean 10% [SE 2.2], 30 [6.4], 50 [8.2], and 70 [13.2] after
      1, 2, 3, and 4 mM 5-ALA, respectively). Reovirus with PpIX-mediated photodynamic
      therapy resulted in a significantly increased cytotoxic effect compared with
      reovirus monotherapy and photodynamic therapy (p=0.042) with 100% cell death
      observed across pancreatic cell lines with 10 PFU per cell combined with 1 and 2
      mM 5-ALA. There was no difference in cytotoxicity observed between added reovirus
      before or after photodynamic therapy. INTERPRETATION: To our knowledge, this is
      the first in-vitro study to combine reovirus oncolytic viral therapy with PpIX
      mediated photodynamic therapy to treat pancreatic cancer. These results show a
      significant additive effect in cell killing and they provide initial evidence for
      a novel combined therapeutic intervention. FUNDING: National Institute for Health
      Research.

PMID- 26312879
TI  - Inhibition of complement C3 and fibrinogen interaction: a potential novel
      therapeutic target to reduce cardiovascular disease in diabetes.
AB  - BACKGROUND: Enhanced complement C3 incorporation into the fibrin network in
      diabetes is one mechanism for impaired fibrinolysis and increased thrombosis risk
      in this condition. Our aim was to develop new strategies to modulate fibrinolysis
      in diabetes by interfering with fibrin-C3 interaction. METHODS: To modulate
      interaction between fibrinogen and C3 we used a novel technique by screening
      fibrinogen with a phage display library of 3 billion random, conformational 9AA
      peptides (termed adhirons). The effect of high affinity fibrinogen binding
      adhirons, released by the addition of excess C3, on fibrin clot lysis and
      structure was assessed in turbidimetric assays. Fibrinogen-C3 interactions were
      further studied by peptide microarray techniques and modelled with the website
      PepSite2. FINDINGS: Ten high affinity fibrinogen binding adhirons, released by
      C3, were available for turbidimetric analysis. One adhiron (A6) was found to have
      a sequence homology with C3 and studied further. In the absence of C3, adhiron A6
      failed to modulate fibrin clot lysis time (mean 644 s [SE 13] and 620 [14]
      without and with adhiron A6, respectively). However, adhiron A6 abolished C3
      induced prolongation of clot lysis, reducing mean lysis time from 728 s (SE 25)
      to 632 (24) (p=0.01). The peptide microarray screening of C3 identified two
      peptide motifs within the beta chain of fibrinogen (residues 424-433, 435-445)
      that bound to C3. PepSite2 predicted that adhiron A6 binds to similar areas on
      the beta chain of fibrinogen. INTERPRETATION: Using a novel phage display system,
      we discovered an adhiron that shared sequence homology with C3 and abolished C3
      induced prolongation of fibrin clot lysis by interfering with C3-fibrinogen
      interaction within the beta chain. This technique offers a unique method to
      identify new therapeutic targets for the reduction of diabetes-specific
      thrombosis risk. FUNDING: Sir Jules Thorn Charitable Trust.

PMID- 26312880
TI  - Synthetic lethality in chronic lymphocytic leukaemia with DNA damage response
      defects by targeting the ATR pathway.
AB  - BACKGROUND: DNA damage response (DDR) defects, particularly TP53 and biallelic
      ataxia telangiectasia mutated (ATM) aberrations, are associated with genomic
      instability, clonal evolution, and chemoresistance in chronic lymphocytic
      leukaemia (CLL). Therapies capable of providing long-term disease control in CLL
      patients with DDR defects are lacking. Using AZD6738, a novel ATR inhibitor, we
      investigated ATR pathway inhibition as a synthetically lethal strategy for
      targeting CLL cells with these defects. METHODS: The effect of AZD6738 was
      assessed by western blotting and immunofluorescence of key DDR proteins.
      Cytotoxicity was assessed by CellTiter-Gloluminescence assay (Promega, Madison,
      WI, USA) and by propidium iodide exclusion. Primary CLL cells with biallelic TP53
      or ATM inactivation were xenotransplanted into NOD/Shi-scid/IL-2Rgamma mice.
      After treatment with AZD6738 or vehicle, tumour load was measured by flow
      cytometric analysis of infiltrated spleens, and subclonal composition by
      fluorescence in-situ hybridisation for 17p(TP53) or 11q(ATM) deletion. FINDINGS:
      AZD6738 provided potent and specific inhibition of ATR signalling with
      compensatory activation of ATM/p53 pathway in cycling CLL cells in the presence
      of genotoxic stress. In p53 or ATM defective cells, AZD6738 treatment resulted in
      replication fork stalls and accumulation of unrepaired DNA damage, as evidenced
      by gammaH2AX and 53BP1 foci formation, which was carried through into mitosis,
      resulting in cell death by mitotic catastrophe. AZD6738 displayed selective
      cytotoxicity towards ATM or p53 deficient CLL cells, and was highly synergistic
      in combination with cytotoxic chemotherapy. This finding was confirmed in primary
      xenograft models of DDR-defective CLL, where treatment with AZD6738 resulted in
      decreased tumour load and selective reduction of CLL subclones with ATM or TP53
      alterations. INTERPRETATION: We have provided mechanistic insight and
      demonstrated in-vitro and in-vivo efficacy of a novel therapeutic approach that
      specifically targets p53-null or ATM-null CLL cells. Such an approach can
      potentially help to avert clonal evolution, a major cause of therapeutic
      resistance and disease relapse. FUNDING: Leukaemia & Lymphoma Research.

PMID- 26312881
TI  - Characteristics of immunosuppressive regulatory T cells in cutaneous squamous
      cell carcinomas and role in metastasis.
AB  - BACKGROUND: Non-melanoma skin cancer is the most common cancer worldwide, and
      cutaneous squamous cell carcinomas (SCCs) account for substantial morbidity and
      mortality because of their potential for metastasis. SCCs are surrounded by an
      immune cell infiltrate containing regulatory T cells (Tregs). The aim of this
      study was to characterise Tregs in SCCs and investigate whether increased Treg
      numbers in primary skin SCCs are associated with subsequent metastasis. METHODS:
      Lymphocytes were extracted from freshly excised skin SCC tumours and
      corresponding peripheral blood and normal skin. Flow cytometry was used for T
      cell analysis and cell sorting. Tritiated thymidine based lymphocyte
      proliferation assays and interferon gamma (IFNgamma) ELISPOT assays were used to
      assess peritumoral lymphocyte function in vitro. Immunohistochemistry was
      performed on primary cutaneous SCC sections from tumours that subsequently
      metastasised and from those that did not after 5-year follow-up. FINDINGS:
      Increased frequencies of CD3+CD4+CD25hiCD127loFOXP3+ Tregs were found in SCCs
      (21.5% of CD4+ immune infiltrate, n=60 tumours) compared with corresponding
      peripheral blood (5.4%) and normal skin (7.6%). SCC Tregs expressed significantly
      higher levels of the co-stimulatory molecules OX40 (37.2% of FOXP3+ cell
      population, n=10 tumours) and 4-1BB (12.6%, n=9) than peritumoral non-regulatory
      T cells and Tregs from peripheral blood and normal skin (p=0.0005). The
      inhibitory receptor CTLA4 and the transcription factor Helios were expressed at
      high levels in peritumoral Tregs. SCC Tregs significantly suppressed
      phytohaemagglutinin-stimulated peritumoral CD4+ T-cell proliferation (p=0.005,
      n=10), peritumoral CD8+ T-cell proliferation (p=0.015, n=9), and IFNgamma
      secretion by CD4+ effector T cells (p=0.026, n=10). Increased in-vitro
      proliferation of phytohaemagglutinin-stimulated peritumoral CD4+ T cells was
      shown after the addition of anti-OX40 antibodies (p=0.0078, n=9 tumours) and anti
      4-1BB antibodies (p=0.0039, n=9). Immunohistochemistry showed fewer CD8+ T cells
      in SCCs that metastasised (n=29) than in non-metastatic SCCs (n=26) (28.5% of
      immune infiltrate vs 44.6%%, p<0.0001) and more FOX3+ Tregs (28.5% of immune
      infiltrate vs 49.3%, p<0.0001). INTERPRETATION: Our study shows that
      immunosuppressive Tregs are present in the immune infiltrate of cutaneous SCCs,
      and contribute to ineffective anti-tumour immune responses, thereby permitting
      SCC development and promoting metastasis. FUNDING: Wellcome Trust, National
      Institute for Health Research.

PMID- 26312882
TI  - The effect of trauma on invasive group A streptococcal disease.
AB  - BACKGROUND: Necrotising fasciitis due to invasive group A streptococcus (iGAS) is
      frequently associated with type emm1 isolates, with an attendant mortality of
      40%. Some cases occur in previously healthy individuals with a history of upper
      respiratory tract infection, soft tissue contusion, and no obvious portal of
      entry. Using a new model of mild contusion injury, we set out to determine the
      effect of contusion on iGAS bacterial burden, phenotype, and host cytokine
      response. METHODS: A new model of mild contusion was developed using a weight
      drop device and characterised in two strains of mice, CD1 and FVB/n. The effect
      of contusion on emm1 iGAS infection was assessed in three murine models of
      infection: lower respiratory tract (intranasal challenge of 1 * 10(7) colony
      forming units [CFU] per mouse), intravenous (1 * 10(7). per mouse via the lateral
      tail vein), and muscle (1 * 10(8) CFU per mouse intramuscularly) at three
      timepoints after injury (24, 48, and 72 h). Bacterial burden, host cytokine
      response, and histological changes were analysed. Further molecular work was
      performed to assess the change in bacterial morphology observed after contusion
      injury in the muscle model. Mann-Whitney U test was used to compare differences
      in bacterial burden and cytokine responses between trauma and control groups.
      FINDINGS: Application of a force of 15.7 mJ resulted in histological changes in
      muscle consistent with mild trauma with no evidence of overlying skin injury, no
      bony injury, and minimum cytokine response. Contusion to soft tissue had no
      effect on bacterial burden or cytokine response in a mouse model of systemic
      infection (after intravenous inoculation) at three timepoints. Despite
      bacteraemia, specific seeding of the contused tissue did not occur in this model.
      By contrast, blunt contusion affected progression of a subsequent local GAS
      muscle infection and increased dissemination to blood in the lower respiratory
      tract infection model. Specifically, contusion increased emm1 GAS dissemination
      locally to draining lymph nodes (controls median 183 CFU per node [IQR 8-5800] vs
      trauma group 20 000 [1875-601 250]). Dissemination to lymph node was linked to a
      phenotypic change in bacterial capsule morphology. This phenotypic change was
      stable despite passage, consistent with a genetic change, and was associated with
      an increase in bacterial hyaluronan production (mucoid colonies 200 MUg per CFU
      and no detectable capsule production in the non-mucoid colonies). INTERPRETATION:
      We found that non-penetrating trauma was associated with an enhanced
      susceptibility to invasive GAS disease. This model of mild contusion did not
      provide a focus for initiation or seeding of bacteraemic infection but instead
      provided an environment that determined the phenotype of the bacteria and
      enhanced local dissemination after iGAS infection at the same site. The
      environmental and genetic cues underlying dissemination are the subject of
      continuing research. FUNDING: Royal Army Medical Corps, Surgeon General's
      Research Strategy Group, Ministry of Defence.

PMID- 26312883
TI  - Physical health indicators in major mental illness: data from the Quality and
      Outcome Framework in the UK.
AB  - BACKGROUND: In the UK, the Quality and Outcome Framework (QOF) has specific
      targets for general practictioners to record body-mass index (BMI) and blood
      pressure (BP) in major mental illness, diabetes, and chronic kidney disease.
      Although incentives are given for aspects of major mental illness (schizophrenia,
      bipolar disorder, and related psychoses), barriers to care can occur. Our aim was
      to compare recording of specific targets for BP and BMI in individuals with major
      mental illness relative to diabetes and chronic kidney disease across the UK.
      METHODS: Using 2012 and 2013 QOF data from 9731 general practices across all four
      countries in the UK, we calculated median payment, population achievement, and
      exception rates for BP indicators in major mental illness and chronic kidney
      disease and BMI indicators in major mental illness and diabetes. Differences in
      unweighted rates between practices in the same UK country were tested with a sign
      test. Differences in population achievement rate between practices in different
      countries were compared with those in England by use of a quantile regression
      analysis. FINDINGS: UK payment and population achievement rates for BMI recording
      in major mental illness were significantly lower than were those in diabetes
      (payment 92.7% vs 95.5% and population achievement 84.0% vs 92.5%, p<0.0001) and
      exception rates were higher (8.1% vs 2.0%, p<0.0001). For BP recording, UK
      payment and population achievement rates were significantly lower for major
      mental illness than for chronic kidney disease (94.1% vs 97.8% and 87.0% vs
      97.1%, p<0.0001), whereas exception rate was higher (6.5% vs 0.0%, p<0.0001).
      This difference was observed for all UK countries. Median population achievement
      rates for BMI and BP recording in major mental illness were significantly lower
      in Scotland than in England (for BMI -1.5%, 99% CI -2.7 to -0.3, and for BP 
      1.8%, -2.7 to -0.9; p<0.0001 for both). There were no cross-jurisdiction
      differences for chronic kidney disease and diabetes. INTERPRETATION: We found
      lower payment rates, higher exception rates, and lower population achievement
      rates for BMI and BP recording in major mental illness than in diabetes and
      chronic kidney disease throughout the UK. We also found variation in these rates
      between countries. This finding is probably multifactorial, reflecting a
      combination of patient, clinician, and wider organisational factors; however, it
      might also suggest inequality in access to certain aspects of health care for
      people with major mental illness. FUNDING: None.

PMID- 26312884
TI  - Role of ANO4 in regulation of aldosterone secretion in the zona glomerulosa of
      the human adrenal gland.
AB  - BACKGROUND: Cell origin of aldosterone-producing adenomas, a major cause of
      hypertension, is unknown. A less common subtype of these adenomas, composed of
      cells resembling zona glomerulosa, have mutations in genes ATP1A1 and CACNA1D. To
      understand whether the adenomas originate from zona glomerulosa, we carried out a
      microarray analysis comparing transcriptomes of zona glomerulosa, zona
      fasciculata, and tumour in human adrenal tissue, and investigated the functional
      role of genes upregulated in the zona glomerulosa. METHODS: Using a microarray
      analysis (Affymetrix, High Wycombe, UK), we compared transcriptomes of zona
      glomerulosa, zona fasciculata, and tumour obtained by laser capture
      microdissection of 14 patients with aldestosterone adenomas and seven with
      phaeochromocytoma. One of the most zona glomerulosa-selective genes was ANO4, a
      member of the anoctamin family. Subcellular localisation was observed by
      immunofluorescence microscopy of transfected HEK293 cells. Yellow fluorescent
      protein-based assay was performed to detect ANO4 activity as a calcium-activated
      chloride channel. H295R cells were transfected by ANO4 to measure aldosterone and
      CYP11B2 expression. FINDINGS: Microarray analysis revealed 28 genes that were at
      least five times overexpressed in zona glomerulosa compared with zona
      fasciculata. ANO4 was 19.9 times higher in zona glomerulosa than in zona
      fasciculata (p=6.6 * 10(-24)). Haemagglutinin-tagged ANO4 was localised to the
      plasma membrane of transfected HEK293 cells. In response to increased
      intracellular calcium, ANO4-transfected cells triggered a lower flow of iodide
      than did other anoctamins. ANO4 overexpression in H295R cells increased
      aldosterone secretion from mean 0.9 pmol/MUg protein (SE 0.2) to 1.1 (0.1),
      whereas CYP11B2 mRNA expression increased five times. INTERPRETATION: We show
      that ANO4 is one of the most highly expressed genes in zona glomerulosa of the
      human adrenal gland. When overexpressed in vitro, it increases aldosterone
      production. FUNDING: British Heart Foundation.

PMID- 26312885
TI  - Association between hypercortisolaemia and adipose tissue blood flow in vivo.
AB  - BACKGROUND: An apple-shaped fat distribution is associated with an adverse
      cardiometabolic phenotype. Hypercortisolaemia (Cushing's syndrome) is
      characterised by abdominal fat accumulation and gluteofemoral fat loss. The
      mechanisms underpinning this redistribution of fat mass are unknown. Since
      adipose tissue blood flow (ATBF) is an important determinant of lipolytic rate in
      vivo, we hypothesised that hypercortisolaemia might lead to differential
      abdominal and femoral ATBF. METHODS: Six healthy male volunteers (median age 25
      years [IQR 20-50], median body-mass index 27.0 kg/m(2) [24.4-29.1]) were
      recruited. Abdominal and femoral ATBF were studied in vivo by use of the
      radioactive xenon washout technique after a hydrocortisone infusion (2 mg/kg per
      min for 16 h) or saline (control). Infusions were given in a randomised double
      blind manner. On each of 2 study days ATBF was studied in the fasting state and
      after a 75 g glucose drink. FINDINGS: Under control conditions, there was no
      difference between fasting or postprandial abdominal and femoral ATBF.
      Hypercortisolaemia increased fasting femoral ATBF (time-averaged area under the
      curve, from a median of 1.6 mL/min per 100 g tissue [IQR 1.2-4.4] to 4.3 [2.7
      5.9], Wilcoxon signed rank test p=0.08), increased postprandial femoral ATBF (2.4
      [1.6-4.0] to 6.9 [3.4-8.7], p=0.046), increased abdominal fasting ATBF (2.2 [1.8
      6.2] to 3.0 [1.7-7.5], p=0.465), and increased abdominal postprandial ATBF (3.5
      [1.9-4.2] to 4.7 [2.1-9.0], p=0.225). Total ATBF time-averaged area under the
      curve response to hypercortisolaemia showed a strong negative correlation with
      waist to hip ratio (Spearman's r abdomen -0.986, p<0.0001; femoral -0.928,
      p=0.008). INTERPRETATION: We showed that hypercortisolaemia increases ATBF, most
      strikingly in the gluteofemoral depot, an effect further augmented in the
      postprandial state. This finding might point to depot specificity of
      glucocorticoid responses and insulin interactions. Depot-specific responses might
      lead to differential fatty acid fluxes in the abdominal and gluteofemoral depot,
      resulting in the fat distribution changes associated with Cushing's syndrome.
      FUNDING: Society for Endocrinology, Wellcome Trust Institutional Strategic
      Support Fund.

PMID- 26312886
TI  - Comparative effectiveness and safety of image guidance systems in surgery: a
      preclinical randomised study.
AB  - BACKGROUND: Over the past decade image guidance systems have been widely adopted
      in specialties such as neurosurgery and otorhinolaryngology. Nonetheless, the
      evidence supporting the use of image guidance systems in surgery remains limited.
      New augmented reality systems offer the possibility of enhanced operating room
      workflow compared with existing triplanar image displays, but recent studies have
      highlighted several concerns, particularly the risk of inattentional blindness
      and impaired depth perception. The aim of this study was to compare
      simultaneously the effectiveness and safety of various image guidance systems
      against standard surgery. METHODS: In this preclinical randomised study design 50
      novice surgeons were allocated to no image guidance, triplanar display, always-on
      solid overlay, always-on wire mesh overlay, or on-demand inverse realism overlay.
      Each participant was asked to identify a basilar tip aneurysm in a validated
      model head. The primary outcomes were time to task completion, and tool path
      length. The secondary outcomes were recognition of an unexpected finding (a
      surgical clip) and subjective depth perception (using a Likert scale). FINDINGS:
      Surgeons' time to task completion and tool path length were significantly lower
      in groups using any form of image guidance than in groups with no image guidance
      (p<0.001 and p=0.003, respectively). The tool path distance was also lower in
      groups using augmented reality than in those using triplanar display (p=0.010).
      Always-on solid overlay resulted in the greatest inattentional blindness (20%
      recognition of unexpected finding by all surgeons). Wire mesh and on-demand
      overlays mitigated but did not negate inattentional blindness, and were
      comparable with triplanar display (40% recognition of unexpected finding in all
      groups). Wire mesh and inverse realism overlays also resulted in better
      subjective depth perception than always-on solid overlay (p=0.031 and p=0.008,
      respectively). INTERPRETATION: This study suggests that new augmented reality
      platforms incorporating always-on wire mesh and on-demand inverse realism might
      improve surgical performance, at least in novice surgeons. All image display
      modalities, including existing triplanar display, carry a risk of inattentional
      blindness. FUNDING: Wellcome Trust.

PMID- 26312887
TI  - Effect of a GRIN2A de novo mutation associated with epilepsy and intellectual
      disability on NMDA receptor currents and Mg(2+) block in cultured primary
      cortical neurons.
AB  - Background GRIN2A encodes the GluN2A subunit of the NMDA receptor (NMDAR), an
      ionotropic glutamate receptor that has important roles in synaptogenesis and
      synaptic plasticity. Some individuals with early onset epilepsies and
      intellectual disability carry heterozygous missense mutations in this gene,
      including a de-novo mutation in the receptor pore region (GluN2A(N615K)). We
      hypothesised that this mutation underlies the carrier's brain disorder and sought
      to explore its functional consequences. METHODS: We made two-electrode voltage
      clamp recordings from Xenopus laevis oocytes expressing GluN1/GluN2A(N615K)
      (N615K) NMDARs and compared them with wild-type (WT) NMDARs to assess the
      mutation's effect on potency of inhibition by Mg(2+) and other channel blockers.
      We then used whole-cell patch-clamping to evaluate NMDAR-mediated currents in
      mouse primary cortical pyramidal neurons transfected with either GluN2A(WT) or
      GluN2A(N651K) subunits. Means were compared by use of independent two-tailed t
      tests. FINDINGS: In oocytes, Mg(2+) (1 mM) block at -60 mV was significantly
      decreased (N615K [n=13], mean 5% [SE 8] vs WT [n=15], 89 [4]; p<0.0001).
      Furthermore, in N615K (n=17) and WT (n=17) oocytes, block by 10 MUM memantine was
      also reduced (mean 26% [6] vs 75 [7], p<0.0001) as was block by 100 MUM
      amantadine (18% [4] vs 44 [12], p<0.0001). Block by ketamine (N615K, n=14; WT,
      n=14) was not significantly affected, whereas block by dextromethorphan was
      increased (N615K [n=9], 56% [8] vs WT [n=8], 44 [6]; p=0.003). In N615K (n=10)
      and WT (n=10) neurons we observed a significant decrease in Mg(2+) sensitivity
      (49% [18] vs 95 [5], p<0.0001) and a significant decrease in current density (42
      pA/pF [19] vs 61 [20], p=0.044). INTERPRETATION: This study suggests that the
      disease-associated mutation GluN2A(N615K) has substantial effects on NMDAR
      inhibition by both endogenous and exogenous channel blockers, and on NMDA current
      density. It is plausible that these changes underlie the carrier's phenotype.
      FUNDING: Wellcome Trust via an Edinburgh Clinical Academic Training PhD
      Fellowship.

PMID- 26312888
TI  - Antagonism of aminoacid transport in primary CD4 T cells by HIV-1 Vpu.
AB  - BACKGROUND: Less than 100 years since it was first transmitted to the human
      population HIV-1 infects more than 30 million people worldwide and causes almost
      2 million AIDS-related deaths every year. Viruses manipulate cellular genes and
      pathways to benefit their survival, and the study of cell surface proteins
      downregulated by viruses has provided insights into both viral pathogenesis and
      crucial aspects of cell biology. We aimed to identify novel cell surface proteins
      targeted for downregulation by HIV-1. METHODS: We combined plasma membrane
      enrichment through selective aminooxybiotinylation with tandem mass tag-based
      quantitative proteomics (plasma membrane profiling) to map expression timecourses
      of more than 800 plasma membrane proteins in T cells infected in vitro with HIV
      1. Novel substrates of the viral accessory proteins Vpu and Nef were sought by
      use of deletion viruses and single gene overexpression. FINDINGS: Our proteomic
      datasets defined more than 100 previously unsuspected cell surface targets of HIV
      1, particularly proteins involved in T-cell activation, cell adhesion, and
      aminoacid transport. In addition to its known targets, Vpu was found to be
      necessary and sufficient for the downregulation of the aminoacid transporter
      TOV3. Downregulation of TOV3 was post transcriptional, mediated by the beta-TrCP
      ubiquitin E3 ligase and occurred via an endolysosomal pathway. TOV3 was highly
      expressed in primary human CD4 T cells, and depletion of TOV3 by RNA interference
      markedly impaired the mitogenic response to CD3/CD28 stimulation. We identified
      alanine as an endogenous TOV3 substrate, and showed that extracellular alanine
      was crucial for T-cell proliferation. INTERPRETATION: This study suggests that
      TOV3 downregulation is restricted to Vpu variants from the lineage of HIV-1 group
      M viruses giving rise to pandemic AIDS. Antagonism of alanine transport in CD4 T
      cells might contribute to HIV-1 pathogenesis through modulation of virus
      production, impairment of the adaptive immune response, or enhancement of CD4 T
      cell loss. FUNDING: Wellcome Trust, Addenbrooke's Charitable Trust, Raymond and
      Beverly Sackler Foundation.

PMID- 26312889
TI  - Assessment of glycogen phosphorylase isoenzyme BB as a biomarker for pre
      eclampsia and small for gestational age.
AB  - BACKGROUND: Glycogen phosphorylase is a key enzyme in the regulation of glycogen
      metabolism and consists of three isoenzymes, including glycogen phosphorylase
      isoenzyme BB (GPBB). Pre-eclampsia, gestational hypertension, and small-for
      gestational-age (SGA) infants are complications in about 15% of all nulliparous
      pregnancies. Biomarkers for these adverse pregnancy outcomes remain elusive. GPBB
      has been proposed as a potential biomarker for the detection of these adverse
      outcomes. We aimed to investigate this hypothesis. METHODS: Blood samples from
      women with pre-eclampsia or SGA were analysed from the time of disease
      presentation and from samples collected at 15 and 20 weeks' gestation. They were
      compared with control samples obtained from women recruited to the Screening for
      Pregnancy Endpoints (SCOPE) study. These control samples were from healthy women
      with uncomplicated pregnancies matched for age, ethnicity, parity, body-mass
      index, and gestational age. GPBB concentrations were measured with ELISA
      (Diacordon, Diagenics, Essen, Germany). FINDINGS: Significant differences in GPBB
      were observed between all three gestations (p=0.03). GPBB concentrations were
      higher in women with pre-eclampsia than in controls at the time of disease
      presentation (term pre-eclampsia n=14, median 22.2 ng/mL [IQR 15.1-39.8] vs 16.9
      [10.4-19.1], p=0.04; preterm pre-eclampsia n=11, 23.1 [11.2-30.9] vs 17.2 [9.8
      19.1], p=0.04) and at 20 weeks' gestation (n=39, 23.0 [15.6-31.4] vs 17.0 [13.4
      23.6]; p=0.04). GPBB concentrations were also significantly higher in women with
      SGA than in controls at the time of disease detection (n=23, 22.7 [12.6-25.5] vs
      17.0 [9.8-18.0]; p=0.03) but significantly less than in controls at 15 weeks'
      gestation before disease detection (n=25, 16.0 [12.1-23.2] vs 22.2 [17.0-28.9];
      p=0.02). INTERPRETATION: We have shown that significant variation of GPBB
      concentrations occurs in normal pregnancy, pre-eclampsia, and SGA pregnancies.
      GPBB in healthy pregnancy lowers as pregnancy progresses from the first to the
      third trimester. GPBB might, therefore, be useful as a biomarker in early
      pregnancy and at the time of disease in the prediction of both preterm and term
      pre-eclampsia and SGA. FUNDING: National Institute for Health Research, SCOPE
      Study was funded by the Health Research Board. This work was performed in the
      Irish Centre for Fetal and Neonatal Translational Research and partly supported
      by Science Foundation Ireland.

PMID- 26312890
TI  - Can encapsulated glutamine increase GLP-1 secretion, improve glucose tolerance,
      and reduce meal size in healthy volunteers? A randomised, placebo-controlled,
      cross-over trial.
AB  - BACKGROUND: Obesity is a global concern and can be effectively treated with
      bariatric surgery, which is expensive and invasive. Weight loss after surgery has
      been attributed to increased nutrient delivery to the lower small intestine with
      release of satiety-promoting gut hormones such as glucagon-like peptide 1 (GLP
      1). We aimed to assess whether glutamine, a potent secretagogue of GLP-1 in vivo,
      increases GLP-1 release, improves glucose tolerance, or reduces meal size in
      volunteers. METHODS: A single-centre, randomised, double blind, placebo
      controlled, cross-over study was performed in Cambridge, UK, studying the effects
      of a single dose of encapsulated ileal-release glutamine (6 g) and placebo
      (microcrystalline cellulose) in healthy adult volunteers. Volunteers were
      recruited for each endpoint and received each regimen in random order (performed
      by electronic random number generation). The primary outcome was within-person
      GLP-1 in venous blood (concentrations and area under the curve). Secondary
      outcomes were glucose tolerance (measured with an oral glucose tolerance test
      given after 90 min) and meal size (ad-libitum meal given at 120 min). Inclusion
      of 8-10 participants for each endpoint would achieve 90% power with alpha at
      0.05. Significance testing was done with the paired t test. Participants gave
      written informed consent and the study was approved by the local research ethics
      committee. This trial is registered with the ISRCTN register, number
      ISRCTN10757078. FINDINGS: 11 men and 13 women were recruited (aged 22-58 years,
      body-mass index 18.5-31.8 kg/m(2)). Ten patients were assigned to assessment of
      GLP-1, eight to assessment of glucose tolerance, and ten for meal size. Some
      volunteers participated in more than one part of the study. Ingestion of 6 g
      glutamine was associated with increased GLP-1 concentrations after 90 min
      compared with placebo (mean 3.2 pmol/L [SD 0.86] vs 2.1 [0.65], p=0.004),
      increased insulin concentrations after 90 min (70.9 [37.9] vs 51.5 [23.1],
      p=0.048), and increased meal size at 120 min (542 g eaten [188] vs 481 [193],
      p=0.008). No safety concerns were identified after the ingestion of glutamine.
      INTERPRETATION: This trial shows that a single oral dose of encapsulated
      glutamine can promote increased secretion of GLP-1 and is associated with
      increased insulin release. However, the effect size was small and unlikely to be
      clinically useful. Glutamine was associated with increased meal size, an
      undesirable effect, perhaps because the orexigenic effects of insulin release
      predominated over the anorexigenic effects of GLP-1 release after administration
      of glutamine. FUNDING: European Union's Seventh Framework Programme, Wellcome
      Trust Translational Medicine & Therapeutics Programme, National Institute for
      Health Research.

PMID- 26312891
TI  - Use of induced pluripotent stem-cell technology to understand photoreceptor
      cytoskeletal dynamics in retinitis pigmentosa.
AB  - BACKGROUND: Retinitis pigmentosa, which affects one in 3000 people, causes
      blindness and has no treatment. Mutations in the retinitis pigmentosa GTPase
      regulator (RPGR) gene cause 20% of all cases. Recent work suggests that RPGR,
      localised to the photoreceptor connecting cilium, regulates rhodopsin transport
      to the outer segment through its effect on the turnover of actin. We set out to
      establish a novel model for RPGR disease to test the hypothesis that RPGR
      mutations lead to retinal degeneration due to a dysregulation of the actin
      cytoskeleton. METHODS: Patients with RPGR mutations and their unaffected
      relatives were recruited and skin biopsy samples taken. Fibroblast lines were
      established and reprogrammed to generate induced pluripotent stem cell (iPSC)
      lines. A three-dimensional organogenesis protocol was optimised whereby embryoid
      bodies were formed and patterned towards an eye field fate in a 100-day retinal
      differentiation protocol, allowing three-dimensional optic cups to form. RPGR
      mutated cultures were compared with their healthy controls. FINDINGS: Mutant and
      wild-type iPSC lines were generated and characterised. Differentiation of all
      lines resulted in the generation of optic cups in a self-organising manner after
      100 days in culture. These cultures contained mature photoreceptors, as evidenced
      by morphology and both RNA and protein expression. Photoreceptor cultures from
      RGPR-mutated iPSCs had increased actin polymerisation compared with controls
      (mean confocal pixel intensity count 59.02 [SD 16.24] vs 23.70 [8.20], p=0.0081).
      This finding was confirmed by assessment of F-actin with western blot. Pathways
      regulating actin turnover were explored; western blot analysis showed a reduction
      in both Src and ERK phosphorylation in RGPR-mutated photoreceptor cultures. An
      unbiased protein array confirmed this reduction in ERK and Src activation.
      Several other pathways were also shown to be dysregulated in the RGPR-mutated
      photoreceptor cultures. INTERPRETATION: This study supports the hypothesis that
      RPGR mutations lead to actin dysregulation. We have identified several pathways
      that are interrupted in RPGR-mutant photoreceptor cultures and could be
      contributing to disease. This study is the first use, to our knowledge, of human
      iPSCs with retinitis pigmentosa-causing mutations to look at pathophysiology of
      disease. FUNDING: Wellcome Trust.

PMID- 26312892
TI  - Access to food retail outlets in County Durham, UK: a pragmatic cross-sectional
      study.
AB  - BACKGROUND: Strong links exist between deprivation, obesity, and dietary quality.
      Increasing interest has focussed on the concept of access to food and so-called
      food deserts, defined by a policy working group of the UK Low Income Project Team
      in 1995 as "areas of relative exclusion where people experience physical and
      economic barriers to accessing healthy food". We aimed to establish the
      accessibility of food retail outlets in County Durham, a county in north-east
      England, UK, considering physical access, affordability, and food range and
      quality. METHODS: In a pragmatic cross-sectional study in County Durham, we used
      information from town surveys and food business databases to locate and identify
      food retail outlets. The prevalence of deprivation, obesity, retail outlets,
      takeaway outlets, and ratio of retail to takeaway outlets was mapped, to
      establish local food access, and any associations with deprivation and obesity.
      The times taken to travel from residences to supermarkets using private car and
      public transport were also measured. 400 members of the community participated in
      eight focus groups and commissioned on-street surveys. Focus group transcripts
      were reviewed alongside the on-street survey responses to identify key issues.
      FINDINGS: Most residents shopped at least weekly for food (n=368, 92%), used a
      supermarket for their main food shop (372, 93%), travelled for up to 15 min (340,
      85%), and used a car for transport (188, 47%). Many survey respondents indicated
      high levels of satisfaction with food retail outlets (average rating 8.7 out of
      10 for agreement with the statement "Overall I am satisfied with the shop where I
      do my main food shopping"), although financial constraints and transport
      inconvenience were identified as barriers. Difficulties with food shopping were
      more widely described in focus groups, and many individuals felt that local
      shopping provision had declined, with an emergent excess of takeaway outlets.
      Food retail access was reduced for the disabled, full-time workers, elderly
      people, and people with children. INTERPRETATION: These findings suggest a
      potential role for individual behaviour change, planning and policy bodies, and
      the food retail industry in addressing food access. The multiple methods used in
      this study enabled triangulation; however, the conclusions are limited by the
      pragmatic nature of data collection and analysis. FUNDING: Durham County Council.

PMID- 26312893
TI  - Mechanisms underlying apathy in Parkinson's disease.
AB  - BACKGROUND: Apathy is a common syndrome observed in many neurological conditions,
      including in up to 70% of patients with Parkinson's disease. Mechanisms
      underlying apathy are poorly understood and clinically we lack robust, objective
      detection methods. We aimed to address this using novel objective measures of
      motivation and reward sensitivity in relation to apathy in patients with
      Parkinson's disease. METHODS: Saccadic velocity and pupil modulation by reward
      were used as objective metrics of motivation in patients with Parkinson's
      disease. In addition, differences in reward sensitivity in patients off
      medication were compared with those on medication, and assessed in relation to
      apathy. 20 patients with idiopathic Parkinson's disease and 21 healthy
      participants were recruited. Patients were tested in counterbalanced sessions, on
      and off dopaminergic medication. Participants were asked to make saccadic eye
      movements for different monetary rewards, with eye position, velocity, and pupil
      diameter monitored with an infrared eye tracker. Faster initiation of saccades
      received a greater proportion of rewards. Apathy was indexed by Lille Apathy
      Rating Scale (LARS) scores. FINDINGS: Healthy controls and patients on medication
      demonstrated an increase in saccadic peak velocity as reward magnitude increased
      (an increase by 41 deg/s [SE 20] p<0.0001, and 22.5 [4.7] p<0.0001,
      respectively). This reward sensitivity was lost in patients off medication (5.2
      [3.2], p=0.117). In all groups, pupil diameter dilated more with larger rewards
      (p<0.05). In Parkinson's diease, pupil reward sensitivity was greater in patients
      on medication than off medication, but not statistically so (p=0.06). A median
      split of patients on medication into high motivated and low motivated groups
      based on LARS scores revealed a significant interaction between motivation level
      and rewards for saccadic peak velocity (F2,18=5.153, p=0.049), with the apathetic
      (low motivation) group exhibiting less reward sensitivity in saccadic peak
      velocity. INTERPRETATION: These findings demonstrate that saccadic velocity and
      pupil diameter are affected by reward magnitude and that the degree of modulation
      varies with motivation levels across individuals. These indices provide a novel
      behavioural measure for probing disorders of motivation in neurological disorders
      such as Parkinson's disease. Dopaminergic medication might be an effective
      treatment for apathy by increasing reward sensitivity, independent of effects on
      motor control. FUNDING: Wellcome Trust.

PMID- 26312894
TI  - The role of BUB and CDC proteins in low-grade breast cancers.
AB  - BACKGROUND: The drivers of neoplasia within low-grade luminal breast cancers
      remain undelineated. The BUB and CDC family are among kinase genes known recently
      to help to identify luminal breast cancers with poorer prognosis. Additionally,
      other CDC kinase genes (CDC42) are associated with luminal A breast cancers with
      good prognosis. We aimed to investigate the role of these kinases at the protein
      level within low-grade luminal breast cancers. METHODS: The Nottingham Tenovus
      Primary Breast Cancer Series (n=1858) microarrays were immunostained for BUB
      (BUB1, BUB1B, BUB3) and CDC proteins (CDC2, CDC42) and expression correlated with
      clinicopathological and molecular variables and patient outcome (SPSS, version
      22). FINDINGS: On chi(2) analysis, cytoplasmic BUB1 and nuclear BUB3 were
      negatively associated with grade including pleomorphism, mitosis, and Nottingham
      Prognostic Index, whereas BUB1B was positively associated (p=0.05). BUB1 and BUB3
      expression was positively correlated with oestrogen and progesterone receptor
      expression whereas BUB1B was negatively correlated (p=0.01). CDC42 had strong
      associations with tumour morphology within the low-grade luminal breast cancers,
      tubular and lobular (p=0.02). CDC42 nuclear expression revealed negative
      correlations with basal (CK5) and HER family biomarkers (p=0.02). By contrast,
      cytoplasmic CDC2 overexpression was associated with high-grade tumours (p=0.01).
      BUB1, BUB1B, and CDC42 showed significant associations (p=0.04) with breast
      cancer-specific survival even at the 15-20-year range, indicating their long-term
      prognostic potential. INTERPRETATION: These results suggest that BUB1, BUB3, and
      CDC42 are key kinases for low-grade luminal tumours whereas BUB1B and CDC2
      kinases are preferentially expressed in high-grade disease. High protein
      expression of BUB1, BUB3, and CDC42 in low-grade breast cancers was associated
      with longer overall survival whereas lower expression resulted in poorer outcome.
      FUNDING: Pathological Society of Great Britain and Northern Ireland, National
      Institute for Health Research.

PMID- 26312895
TI  - Cardiac-targeted NADPH oxidase 4 in the adaptive cardiac remodelling of the
      murine heart.
AB  - BACKGROUND: The mechanisms that determine whether the heart adapts to overload
      stress, or fails, are poorly understood. NADPH oxidase (NOX) proteins produce
      reactive oxygen species (ROS) involved in redox signalling, and our recent
      studies have found that an increase in Nox4 during pressure overload protects the
      heart against failure. We aimed to identify novel Nox4-driven cardioprotective
      mechanisms that promote adaptive cardiac remodelling. METHODS: We first undertook
      a proteomic comparison of heart tissue from cardiac-targeted Nox4-overexpressing
      mice and controls. The Nox4 cardiac metabolome was then investigated by (1)H
      nuclear magnetic resonance (NMR) spectroscopy. Effects on cardiac metabolism were
      assessed by ex-vivo working heart perfusions and isolated mitochondrial
      respiration studies. Ex-vivo cardiac energetics were assessed by (31)P NMR.
      Alterations to cardiac fatty acid oxidation were explored in primary
      cardiomyocytes (extracellular flux analysis). FINDINGS: Cardiac-targeted Nox4
      overexpression profoundly remodelled the cardiac proteome in an isoform-specific
      manner, both in the unstressed and stressed heart. Glycolysis and fatty acid
      oxidation were identified as the most enriched pathways that were altered by
      Nox4. Metabolomic analysis showed a 2.2 times increase in acetylcarnitine
      concentrations (p=0.002). Ex-vivo heart perfusions demonstrated a profound
      increase in palmitate oxidation relative to wild-type hearts (3.6 times increase,
      p=0.01), with opposite findings observed in primary cardiomyocytes with a
      knockdown of Nox4. A preference for fatty acid oxidation in Nox4 hearts
      correlated with a better energetic state (phosphocreatine:ATP ratio) when
      subjected to increasing doses of isoprenaline stress under baseline and pressure
      overload. INTERPRETATION: In this study we identified a novel role for Nox4 in
      the regulation of cardiac fatty acid oxidation. Cardiomyocyte-targeted Nox4
      hearts preferentially oxidised fatty acids for energy provision, improving
      myocardial energetics under stress. Enhancing fatty acid oxidation might have an
      adaptive role in the setting of pressure-overload hypertrophy. These data provide
      novel insights into ROS-dependent metabolic programming. FUNDING: UK Medical
      Research Council, British Heart Foundation.

PMID- 26312896
TI  - Factors associated with early provision of respiratory support in deteriorating
      ward patients with chest sepsis.
AB  - BACKGROUND: Implementation of the National Early Warning Score in the National
      Health Service (NHS) has renewed focus on prompt identification and referral of
      the deteriorating ward patient. A large body of published work suggests that
      delay in both referral and admission to critical care can be associated with poor
      outcomes. We sought to explore factors associated with early provision of
      respiratory support in a cohort of deteriorating ward patients referred to the
      critical care team. METHODS: SPOT(light) (Sepsis Pathophysiological and
      Organisational Timing) was a prospective observational study carried out between
      2010 and 2011 in acute NHS hospitals in the UK. In a pilot retrospective
      analysis, we merged data from this study with organ support data from the
      Critical Care Minimum Data Set. Deteriorating adult ward patients referred to the
      critical care team with presumed severe chest sepsis and with no treatment
      limitations in place were eligible for inclusion. We used these data to assess
      critical care bed availabilty and factors affecting decisions to accept patients
      to the intensive care unit. FINDINGS: 828 patients at 13 acute hospitals were
      referred to the critical care team. 7-day mortality was 17% (138 patients); 115
      (83%) of these patients had not received inspiratory positive pressure
      ventilation (IPPV) despite having had no treatment limitations in place. 275
      (33%) of the 828 patients were accepted by the critical team after review. A
      decision to accept was significantly more likely when beds were available than
      when not available (269/275 [34%] vs 6/275 [15%], p=0.010). Mean time to
      commencing IPPV was significantly reduced by critical care bed availability (0.8
      days [SD 1.3] vs 2.3 [1.4], p=0.001). 130 patients (16%) received IPPV, of whom
      93 (72%) proceeded directly to IPPV rather than via non-invasive ventilation
      (NIV) initially. Patients were more likely to proceed directly to IPPV where the
      critical care team made a decision to admit (72/93 [77%] vs 21/93 [57%],
      p=0.018). INTERPRETATION: These pilot data suggest that critical care bed
      availability and a decision to admit to critical care are associated with both a
      faster and a more direct provision of IPPV (rather than via NIV initially). In
      this small sample, a large proportion of the mortality occurred in patients who
      had not received IPPV despite having had no treatment limitations in place.
      FUNDING: Wellcome Trust, National Institute for Health Service Support Costs,
      Intensive Care National Audit & Research Centre.

PMID- 26312897
TI  - Use of magnetic nanoparticles and oscillating magnetic field for non-viral gene
      transfer into mouse cornea.
AB  - BACKGROUND: Inherited, iatrogenic, and metabolic corneal disease could be
      potentially treated by supplying a functional gene or changing the expression
      levels of specific genes. Viral-based gene therapy is efficient, but restricted
      by evoking immune responses and inflammation. This study aimed to transfect mouse
      cornea with a non-viral based (oscillating magnetofection) method. METHODS:
      Cultured mouse corneas were treated with magnetic nanoparticles (MNP) tethered to
      CAG promoter and green fluorescent protein (GFP) reporter plasmids exposed to a 1
      Hz, 2 Hz, and 4 Hz oscillating magnetic field for 30 min and 60 min and in three
      DNA:MNP ratios (1:2, 1:1, 2:3). Corneas were cultured for up to 3 days and their
      green fluorescent channel intensity and number of GFP-positive cells were
      recorded. Transfection efficiency was estimated as the percentage of GFP-positive
      cells per total cells in a microscopic field. FINDINGS: Control experiments with
      absent magnetic exposure showed no GFP-positive cells. The optimum condition was
      recorded at 3:2 DNA:MNP ratio, 1 Hz magnetic oscillation, and 30 min duration of
      magnetic exposure (mean GFP-positive endothelial cell count 191.7 [SD 54.5],
      p=0.009; mean green fluorescent intensity 85.3 [SD 48.5]; and average
      transfection efficiency 23.3% [range 10.6-30.9]). INTERPRETATION: A novel non
      viral method of transfecting cornea, magnetofection, is demonstrated and gives
      proof of principle for its translation into corneal gene therapy. FUNDING: Welsh
      Clinical Academic Training Scheme.

PMID- 26312898
TI  - Which children and young people are excluded from school? Findings from the Avon
      Longitudinal Study of Parents and Children (ALSPAC).
AB  - BACKGROUND: School exclusion is a disciplinary method used to remove a child from
      the school environment. It is known to affect certain groups disproportionately,
      including boys, some ethnic minorities, children in care, children in poverty,
      and children with special educational needs. Population-based studies on wider
      characteristics of excluded pupils are scarce. The aim of this study was to
      describe factors associated with school exclusion in the Avon Longitudinal Study
      of Parents and Children (ALSPAC), focussing on neurodevelopment and mental
      health. METHODS: ALSPAC is a prospective population-based British birth cohort
      study, with the initial sample consisting of 14 541 pregnancies. The study has
      data for whether a child has been permanently excluded from school up to the age
      of 8 years as reported by parents and also permanent and fixed period exclusions
      in the preceding 12 months as reported by parents and young people at age 16
      years. Upstream risk factors were assessed for associations with exclusion on
      univariable analysis. The association with social communication difficulties was
      investigated with multivariable logistic regression. FINDINGS: Data for
      exclusions up to the age of 8 years were available for 8245 ALSPAC participants
      and 4482 participants for exclusion at age 16 years. 53 pupils (0.6%) were
      excluded from school by age 8 years, and 390 (8.7%) at age 16 years. The odds of
      exclusion by 8 years and at 16 years were increased with male sex (p=0.001 and
      p<0.0001, respectively), low family income (p=0.014 and p<0.0001), family
      adversity (p<0.0001 for both), maternal psychopathology (p=0.013 and p=0.004),
      low intelligence quotient (p=0.041 and p<0.0001), mental health difficulties
      (p<0.0001 for both), psychiatric disorder (p<0.0001 for both), social
      communication difficulties (p<0.0001 for both), antisocial activities (p=0.004
      and p<0.0001), bullying or being bullied (p=0.005 and p<0.0001), low educational
      attainment (p<0.0001 for both), and increased special educational needs (p<0.0001
      for both). On multivariable analysis, having social communication difficulties
      above a clinical threshold on the Social Communication Disorders Checklist was
      strongly associated with exclusion by 8 years (odds ratio 7.4, 95% CI 3.6-15.4)
      and at 16 years (2.3, 1.5-3.5), after adjustment for relevant confounders.
      INTERPRETATION: Although cohort attrition and small numbers of exclusions at 8
      years are limitations, this study suggests that school exclusion is associated
      with numerous risk factors identifiable at or before primary school entry. Child
      health professionals have an important role in the holistic assessment of
      children who are excluded, or who are at risk of school exclusion. There is
      particular need to ensure that mental health and neurodevelopmental difficulties
      are appropriately recognised and supported. FUNDING: National Institute for
      Health Research Academic Clinical Fellowship.

PMID- 26312899
TI  - Phosphoinositide 3-kinase-related overgrowth: cellular phenotype and future
      therapeutic options.
AB  - BACKGROUND: Somatic activating mutations in PIK3CA, which encodes the p110alpha
      catalytic subunit of phosphoinositide-3-kinase (PI3K) are frequently found in
      cancers and have been identified in a spectrum of mosaic overgrowth disorders
      ranging from isolated digit enlargement to more extensive overgrowth of the body,
      brain, or vasculature. We aimed to study affected dermal fibroblasts with a view
      to inform therapeutic studies, and to observe cancer-associated mutations in
      isolation. METHODS: We measured PIP3 concentrations in dermal fibroblasts with
      endogenous PIK3CA mutations and in wild type fibroblasts using mass spectrometry,
      and we measured downstream signalling events with ELISA and immunoblotting.
      Cellular proliferation was evaluated with 5-bromo-2'-deoxyuridine incorporation,
      and cell size assessed by fluorescence-activated cell sorting (FACS). Glycolysis
      and mitochondrial tests were performed with an extracellular flux analyser
      (Seahorse Bioscience, Billerica, MA, USA), and mitochondrial potential was
      measured by FACS-based JC1 staining. Experiments were repeated after exposure to
      5 nmol everolimus for 72 h. FINDINGS: Mutant fibroblasts had two times higher
      basal PIP3 concentrations than wild-type fibroblasts (p=0.0017), with concomitant
      AKT and p70S6 activation downstream. The rate of cellular proliferation was
      higher in mutant cells under low serum conditions, but median cell size was not
      statistically different. Glycolytic capacity was similar between mutant and wild
      type fibroblasts, but subtle differences in mitochondrial function were detected
      with blunted responses to uncoupling agents and reduced membrane potentials.
      Treatment with everolimus reversed aberrant AKT(ser473) and p70S6 signalling,
      slowed cellular proliferation, and reversed mitochondrial abnormalities, but was
      associated, paradoxically, with increases in PIP3 concentrations. INTERPRETATION:
      These experiments demonstrate activation of the PI3K-AKT pathway in affected
      fibroblasts with increased proliferation, but no hypertrophy. Moreover, we
      identified changes in mitochondrial function in keeping with the known propensity
      of AKT to modulate elements of the Warburg effect. These results suggest that
      inhibitors of the mammalian target of rapamycin (mTOR) might be beneficial, but
      these inhibitors will require formal evaluation in clinical trials. More targeted
      therapy with p110alpha inhibitors is an enticing future option. FUNDING: Wellcome
      Trust, Sackler Fund, National Instititute for Health Research.

PMID- 26312900
TI  - Novel plasma microRNA biomarkers for the identification of colitis-associated
      carcinoma.
AB  - BACKGROUND: Ulcerative colitis is an established risk factor for colorectal
      cancer, also known as colitis-associated cancer. Existing colonoscopic-based
      surveillance has many disadvantages, so a new accurate, efficient, cost-effective
      screening test is needed. MicroRNAs (miRNAs) regulate gene expression and are
      dysregulated in a range of diseases, including ulcerative colitis and colorectal
      cancer. This study aimed to establish the miRNAs associated with colitis
      associated cancer. METHODS: Blood samples were collected from 45 adult patients
      undergoing colonoscopic screening for ulcerative colitis at the Leicester General
      Hospital, Leicester, UK. Pool A and B TaqMan Array 384-well cards were used to
      quantify the expression of 754 miRNAs in the circulating plasma. 28 high priority
      miRNA candidates showing abnormal expression were validated with real-time
      quantitative PCR. FINDINGS: Patients were allocated to three disease groups
      (ulcerative colitis, n=37; dysplasia, n=2; colitis-associated cancer, n=6).
      Analysis of variance was used to assess differences between the groups. miR-375
      was significantly upregulated in the colitis-associated cancer cohort (p=0.0061)
      compared with active ulcerative colitis. Combining several miRNAs in a panel
      increased the capacity of the test to distinguish between colitis-associated
      cancer and different ulcerative colitis activity states. INTERPRETATION: Our
      study suggests that miRNAs have the potential to act as blood-based biomarkers to
      monitor the activity and progression of disease in patients with ulcerative
      colitis. FUNDING: Royal College of Surgeons of England.

PMID- 26312901
TI  - Cannabis use and treatment resistance in first episode psychosis: a natural
      language processing study.
AB  - BACKGROUND: Cannabis is frequently used among individuals with first episode
      psychosis and is associated with poor clinical outcomes. However, little is known
      about the effect of cannabis use on the response to antipsychotic medications and
      how use could affect outcomes. Using natural language processing on clinical data
      from a large electronic case register, we sought to investigate whether
      resistance to antipsychotic treatment mediated poor clinical outcomes associated
      with cannabis use. METHODS: Data were obtained from 2026 people with first
      episode psychosis in south London, UK. Cannabis use documented in free text
      clinical records was identified with natural language processing. Data for age,
      sex, ethnicity, marital status, psychotic disorder diagnosis, subsequent hospital
      admission, and number of unique antipsychotic medications prescribed were
      obtained using the Clinical Record Interactive Search instrument. The association
      of these variables with cannabis use was analysed with multivariable regression
      and mediation analysis. FINDINGS: 939 people (46.3%) with first episode psychosis
      were using cannabis at first presentation. Cannabis use was most strongly
      associated with being 16-25 years old, male, and single, and was also associated
      with an increase in number of hospital admissions (incidence rate ratio 1.50, 95%
      CI 1.25-1.80), compulsory hospital admission (odds ratio 1.55, 1.16-2.08), and
      number of days spent in hospital (beta coefficient 35.1 days, 12.1-58.1) over 5
      years' follow-up. An increase in number of unique antipsychotic medications
      mediated an increase in number of hospital admissions (natural indirect effect
      1.11, 1.04-1.17; total effect 1.41, 1.22-1.64), compulsory hospital admission
      (1.27, 1.10-1.45; 1.71, 1.05-2.78), and number of days spent in hospital (16.1,
      6.7-25.5; 19.9, 2.5-37.3). INTERPRETATION: We showed that a substantial number of
      people with first episode psychosis used cannabis and that its use was associated
      with increased likelihood of hospital admission and number of days spent in
      hospital. These associations were partly mediated by an increase in number of
      unique antipsychotic medications prescribed. These findings suggest that cannabis
      might reduce response to conventional antipsychotic treatment and highlight the
      importance of strategies to reduce its use. FUNDING: National Institute for
      Health Research, UK Medical Research Council.

PMID- 26312902
TI  - Arsenic, antimony, and Leishmania: has arsenic contamination of drinking water in
      India led to treatment- resistant kala-azar?
AB  - BACKGROUND: In Bihar state, India, the cure rate of antimonial compounds (eg,
      sodium stibogluconate) in the treatment of visceral leishmaniasis (VL) has fallen
      from more than 85% to less than 50%. This reduction has been attributed to long
      term, widespread misuse of antimonial drugs within the Indian private health-care
      system. We aimed to test the hypothesis that exposure to arsenic in drinking
      water in this region has resulted in antimony-resistant Leishmania parasites.
      METHODS: L donovani parasites were serially passaged in mice exposed to
      environmentally relevant concentrations of arsenic in drinking water. Arsenic
      concentrations in murine organs were quantified and the sensitivity of L donovani
      to sodium stibogluconate assessed at each passage. A retrospective field study on
      a cohort of antimony-treated patients with VL was performed in an arsenic
      contaminated area of Bihar to assess risk of treatment failure and death in
      people exposed to arsenic. FINDINGS: Arsenic accumulation in organs of exposed
      mice was proportional to exposure level. After five passages, isolated parasites
      were refractory to sodium stibogluconate in in-vitro drug sensitivity assays.
      Treatment of arsenic exposed, infected mice with this drug confirmed that these
      parasites retained resistance in vivo. In the field work study, 110 patients with
      VL treated with sodium stibogluconate, failure rate was 59%. Patients using well
      water with high mean arsenic concentrations had a higher risk of treatment
      failure than patients using wells with arsenic levels of less than 10 MUg/L (odds
      ratio 1.78, 95% CI 0.7-4.6, p=0.23). 21 patients died, 16 directly as a result of
      their disease. Mean arsenic concentrations of more than 10 MUg/L increased the
      risk of all-cause and VL-related mortality (hazard ratio 3.27, 95% CI 1.4-8.1,
      and 2.65, 0.96-7.65, respectively). INTERPRETATION: These data suggest that
      arsenic contamination might have contributed to the development of antimonial
      resistance in Leishmania parasites in Bihar. Our epidemiological study was
      underpowered and retrospective in nature, so firm conclusions cannot be made.
      Further research into the associations between arsenic exposure and antimonial
      treatment failure and death in the leishmaniases is warranted. FUNDING: Wellcome
      Trust.

PMID- 26312903
TI  - Dynamics of DNA methylation at IGF2 in preterm and term infants during the first
      year of life: an observational study.
AB  - BACKGROUND: Preterm infants are at increased risk of cardiometabolic disease in
      later life. Extrauterine growth restriction, catch-up growth, altered adiposity,
      and abnormal hypothalamic-pituitary-adrenal axis activity could be predisposing
      factors. Altered DNA methylation (5-methylcytosine, 5mC) might be one underlying
      mechanism. We hypothesised that preterm infants have altered 5mC at the linked
      differentially methylated region 2 (DMR2) of IGF2 and the H19 imprinting control
      region (H19 ICR) compared with term infants over the first year of life. METHODS:
      We recruited 46 preterm (range 25 weeks + 2 days' gestation to 31 + 5, mean 28 +
      6) and 40 term infants (38 + 3 to 42 + 2 weeks' gestation, mean 40 + 2).
      Anthropometric variables including body composition were measured at term age and
      3 months corrected age with air displacement plethysmography and at 1-year
      corrected age with skin-fold thickness. Salivary cortisol was measured at 3
      months corrected age after the physical examination. Percentage methylation
      (%5mC) was analysed with pyrosequencing on buccal DNA. Statistical analysis used
      Student's t test and multivariate linear regression. FINDINGS: Preterm infants
      demonstrated growth deficit early in postnatal life but had greater percentage
      body fat at term age (beta=5.73, p<0.001), but not at 3 months (beta=-0.28,
      p=0.82). Compared with term infants, preterm infants had a blunted cortisol
      response to physical examination (mean difference 0.38 MUg/dL, p=0.024). At
      birth, preterm infants had a significant decrease in %5mC at DMR2 compared with
      term infants at birth (beta=-11.48, p<0.001) and compared with preterm infants at
      term-corrected age (t=3.13, p=0.01). By term-corrected age, preterm infants had
      decreased %5mC at both DMR2 (beta=-2.84, p=0.013) and the H19 ICR (beta=-2.31,
      p=0.048) compared with term infants at birth, although this difference
      disappeared at 1 year. Social deprivation was independently associated with
      decreased %5mC at DMR2 at birth (beta=-1.73, p=0.006) and term-corrected age
      (beta=-0.86, p=0.016) but not at 1 year (beta=-0.89, p=0.07). INTERPRETATION: Our
      results show that decreased %5mC accompanies the early growth deficit in preterm
      infants. The marked reduction in %5mC at IGF2 DMR2 in preterm infants at birth
      compared with term-age supports existing evidence that imprinting at secondary
      regions is established after fertilisation, whereas imprinting is established
      during gametogenesis at primary regions (H19 ICR). Both regions might be
      susceptible to early life stressors such as preterm birth and social deprivation.
      FUNDING: Chief Scientist Office of the Scottish Government.

PMID- 26312904
TI  - Evaluation of the role of miR-31-dependent reduction in dystrophin and nNOS on
      atrial-fibrillation-induced electrical remodelling in man.
AB  - BACKGROUND: The management of atrial fibrillation remains a challenge. This
      condition remodels atrial electrical properties, which promote resistance to
      treatment. Although remodelling has long been a therapeutic target in atrial
      fibrillation, its causes remain incompletely understood. We aimed to evaluate the
      role of miR-31-dependent reduction in dystrophin and neuronal nitric oxide
      synthase (nNOS, also known as NOS1) on atrial electrical properties and atrial
      fibrillation inducibility. METHODS: We recruited 258 patients (209 patients in
      sinus rhythm and 49 with permanent atrial fibrillation) from the John Radcliffe
      Hospital, Oxford, UK; written informed consent was obtained from each
      participant. We also used a goat model of pacing-induced atrial fibrillation (24
      with atrial fibrillation vs 20 controls in normal sinus rythm) and nNos-knock-out
      mice (n=28 compared with 27 wild-type littermates). Gene expression of miR-31,
      dystrophin, and nNOS was assessed by quantitative RT-PCR; protein content was
      measured by immunoblotting; NOS activity was evaluated with high-performance
      liquid chromatography; action potential duration (APD) and rate dependent
      adaptation were assessed by single-cell patch-clamping, and atrial fibrillation
      inducibility was evaluated by transoesophageal atrial burst stimulation.
      FINDINGS: We found that atrial-specific upregulation of miR-31 in human atrial
      fibrillation caused dystrophin (DYS) translational repression and accelerated
      mRNA degradation of nNOS leading to a profound reduction in atrial DYS and nNOS
      protein content and in nitric oxide availability. In human atrial myocytes
      obtained from patients in sinus rhythm, nNOS inhibition was sufficient to
      recapitulate hallmark features of remodelling induced by atrial fibrillation,
      such as shortening of APD and loss of APD rate-dependency, but had no effect in
      patients with atrial fibrillation. In mice, nNos gene deletion or inhibition
      shortened atrial APD and increased atrial fibrillation inducibility in vivo.
      Inhibition of miR-31 in human atrial fibrillation recovered DYS and nNOS, and
      normalised APD and APD rate-dependency. Prevention of miR-31 binding to nNOS
      3'UTR recovered both nNOS protein and gene expression but had no effect on the
      DYS protein or mRNA level (consistent with the mRNA degradation of nNOS by miR
      31). Prevention of miR-31 binding to DYS 3'UTR increased DYS protein but not mRNA
      is consistent with translation repression of DYS by miR-31; recovery of DYS
      protein increased nNOS protein but not mRNA in keeping with a stabilising effect
      of DYS on nNOS protein. In goats, a reduction in dystrophin and nNOS protein
      content was associated with upregulation of miR-31 in the atria but not in the
      ventricles. INTERPRETATION: The findings suggest that atrial-specific
      upregulation of miR-31 in human atrial fibrillation is a key mechanism causing
      atrial loss of dystrophin and nNOS; this loss leads to the electrical phenotype
      induced by atrial fibrillation. FUNDING: British Heart Foundation (BHF) Programme
      grant (for BC and XL), BHF Centre of Excellence in Oxford (SR), Leducq Foundation
      (in part for BC and SR), the European Union's seventh Framework Programme Grant
      Agree.

PMID- 26312905
TI  - Role of vitamin D in endothelial function and endothelial repair in clinically
      stable systemic lupus erythematosus.
AB  - BACKGROUND: Patients with systemic lupus erythematosus (SLE) have endothelial
      dysfunction and increased risk of cardiovascular disease. Endothelium-dependent
      dilatation (ED) is abnormal in patients with SLE, and endothelial repair
      mechanisms are also impaired. Myeloid angiogenic cells (MACs) promote
      angiogenesis to restore damaged vessels. Vitamin D deficiency is associated with
      cardiovascular disease in the general population and is prevalent in SLE. We
      aimed to assess the effect of vitamin D on endothelial repair and function.
      METHODS: Vitamin D deficient (<20 ng/mL) patients with SLE were treated with
      cholecalciferol by their physician. Vitamin D replete patients (>30 ng/mL) and
      healthy controls (>20 ng/mL) were also recruited. Endothelial function was
      determined by the ratio of ED to independent dilatation (EI). MACs from patients
      were cultured with and without 10 nM calcitriol, and function determined by
      migration and angiogenesis assays. Endothelial nitric oxide synthase (eNOS)
      expression was studied in human aortic endothelial cells treated with tumour
      necrosis factor alpha (TNFalpha) and MAC-conditioned media. FINDINGS: We studied
      22 vitamin D deficient and 18 replete patients. Vitamin D deficient patients had
      an increased number of MACs compared with controls (p=0.04) but impaired
      migratory capacity (p=0.001) and reduced angiogenic capacity, although this was
      not statistically significant (p=0.13). Media from calcitriol-treated MACs
      significantly increased angiogenesis compared with untreated MACs (p=0.01).
      Calcitriol reduced IP-10 expression by MACs (p<0.0006), and blockade of IP-10
      restored the angiogenic capacity of MACs from patients with SLE. In
      cholecalciferol-treated patients, change in 25-hydroxyvitamin D was strongly
      correlated with change in ED:EI (r=0.650, p=0.006) after adjustment for age (odds
      ratio 1.12, 95% CI 1.02-1.24; p=0.02). Media from calcitriol-treated MACs more
      strongly attenuated TNFalpha-mediated downregulation of eNOS in human aortic
      endothelial cells than did untreated MACs from patients with SLE (p=0.01).
      INTERPRETATION: In this small experimental study, calcitriol improved endothelial
      function in patients with stable SLE. This improvement was associated with an
      increase in MAC number and function. The improved angiogenic capacity in MACs
      might be mediated via downregulation of IP-10 and changes in ED:EI by MAC
      regulation of eNOS in endothelial cells. The findings suggest that vitamin D
      could be a novel therapy to reduce cardiovascular disease in this patient group.
      FUNDING: North West England Medical Research Council Fellowship Scheme in
      Clinical Pharmacology and Therapeutics (funding from UK Medical Research Council
      (grant number G1000417/94909), ICON, Astra Zeneca, GlaxoSmithKline, Medicines
      Evaluation Unit).

PMID- 26312906
TI  - Feasibility of alcohol misuse screening and treatment in the dental setting.
AB  - BACKGROUND: Dental specialists treat conditions such as facial trauma and oral
      cancer that can result from alcohol misuse. Visits to primary dental care
      professionals are oriented towards prevention. Interventions coordinated by
      specialist services but delivered strategically in primary care could therefore
      potentially help to reduce burdens on secondary care services. The aim of this
      study was to determine the feasibility of screening for alcohol misuse and
      providing brief intervention in a primary dental care setting. METHODS: In this
      randomised controlled trial, patients aged 18-65 years were recruited from a
      local general dental practice. Patients were stratified according to appointment
      (with a dentist or hygienist). Reception staff administered envelope packs
      containing screening materials (the Modified Single Alcohol Screening Question [M
      SASQ]), consent forms, and a short survey collecting contact details to patients
      who agreed to take part in the study. Packs were randomly pre-allocated to
      control and intervention groups by strata using block randomisation before the
      start of the study. Consenting patients scoring positively on the M-SASQ for
      drinking hazardously and allocated to the intervention group received a
      motivational intervention to reduce alcohol intake from either the hygienist or
      dentist. Patients in the control group received usual care. The outcome assessor
      and patients were masked to allocations. The outcome measure at 3 months was M
      SASQ score. This trial is registered with the ISRCTN registry, number
      ISRCTN18745862. FINDINGS: One hygiene patient and 106 dental patients were
      recruited. The hygiene patient did not score positively on the M-SASQ for alcohol
      misuse. Of the 106 dental patients, 46 (43%) scored positively, with 26 allocated
      to the intervention group and 20 to the control group. Follow-up data were
      available for 22 (48%) of the 46 patients (12 intervention, 10 control). M-SASQ
      scores changed from positive to negative for two patients in the intervention and
      five in the control group. INTERPRETATION: Alcohol misuse screening and treatment
      was feasible in a primary dental care setting; this suggests a new approach
      involving the general dental team, which could potentially reduce burdens on
      specialist dental services. Overall, in this practice, the dentist was best
      placed to deliver the intervention rather than the hygienist since these health
      care professionals saw most of the patients recruited into the trial.
      Contamination might have been a problem because more patients in the control
      group changed M-SASQ score. Building on these findings, a multicentre, cluster
      randomised controlled trial is planned. FUNDING: Royal College of Surgeons of
      England.

PMID- 26312907
TI  - Neuronal chloride transport tuning.
AB  - BACKGROUND: Epilepsy is characterised by disturbed neuronal activity in the brain
      rendering it more susceptible to seizures. An understanding of the molecular
      mechanisms by which the balance between excitability and inhibition in neuronal
      networks is controlled will help to devise better treatment options.
      Hyperpolarising synaptic inhibition through GABAA (gamma aminobutyric acid type
      A) and glycine receptors depends on the presence of the neuronal cation-chloride
      cotransporter protein, KCC2. Several transcriptional and post-transcriptional
      mechanisms have been shown to regulate KCC2 and thereby affect the polarity and
      efficacy of inhibitory synaptic transmission. However, it is unknown whether
      regulation of KCC2 enables the transporter to attain different levels of
      activity, thus allowing a neuron to modulate the strength of inhibitory synaptic
      transmission to its changing requirements. We therefore investigated whether
      phosphorylation can allow KCC2 to achieve distinct levels of intracellular
      chloride ion concentrations in neurons. METHODS: A variety of KCC2 alanine
      dephosphorylation mimics were created and NH4(+)-induced pHi shifts were used in
      cultured hippocampal neurons to quantify the rate of KCC2 transport activity
      exhibited by these mutants. The association between KCC2 transport strength and
      GABAA receptor-mediated current amplitudes was investigated by performing
      gramicidine perforated-patch recordings. The correlation between reversal
      potential of GABAergic currents (EGABA) and NH4(+)-induced pHi shifts enabled an
      estimate of the range of chloride extrusion possible by kinase-phosphatase
      regulation of KCC2. Finally, we used the Goldman-Hodgkin-Katz equation to examine
      how EGABA would vary with increasing concentrations of extracellular K(+) in
      neurons expressing KCC2 mutants with different rates of transport. FINDINGS: KCC2
      transport strength varied considerably in magnitude (from -0.02 to -1.00 pHi
      shifts) depending on the combination of alanine mutations present on the protein.
      KCC2 transport strength determined the direction and magnitude of GABAA receptor
      mediated current amplitudes and was observed to have a linear correlation with
      the reversal potential of GABAergic currents. INTERPRETATION: Our findings
      highlight the considerable potential for regulating the inhibitory tone by KCC2
      mediated chloride extrusion. Transport can be enhanced to sufficiently high
      levels that hyperpolarising GABAA responses can be obtained even at high
      extracellular K(+) concentrations and in neurons with an extremely negative
      resting membrane potential. We conclude that cellular signalling pathways might
      act together to alter the state of KCC2 phosphorylation and dephosphorylation and
      thereby tune the strength of synaptic inhibition. FUNDING: Royal Society.

PMID- 26312908
TI  - Type 2 diabetes and incidence of a wide range of cardiovascular diseases: a
      cohort study in 1.9 million people.
AB  - BACKGROUND: The contemporary associations of type 2 diabetes with a wide range of
      incident cardiovascular diseases have not been compared. Previous studies have
      focussed on myocardial infarction and stroke, and these conditions are the usual
      outcomes chosen in clinical trials in type 2 diabetes, but other diseases such as
      heart failure and angina are also major causes of morbidity in diabetes. We aimed
      to study associations between type 2 diabetes and 12 initial manifestations of
      cardiovascular disease. METHODS: We used linked electronic health records from
      1997 to 2010 in the CALIBER (cardiovascular research using linked bespoke studies
      and electronic health records) programme to investigate the absolute and relative
      risks associated with type 2 diabetes in a cohort of 1.92 million patients in
      England. We included patients aged 30 years and older who were free from
      cardiovascular disease at baseline. This study is registered with
      ClinicalTrials.gov, number NCT01804439. FINDINGS: We observed 113 638 first
      presentations of cardiovascular disease during a median follow-up of 5.5 years
      (IQR 2.1-10.1). 34 198 people had type 2 diabetes: 6137 experienced a first
      cardiovascular presentation, of which the most common were peripheral arterial
      disease (16.2%, n=992) and heart failure (14.1%, n=866). Type 2 diabetes was
      strongly positively associated with peripheral arterial disease (adjusted cause
      specific hazard ratio 2.98, 95% CI 2.76-3.22), ischaemic stroke (1.72, 1.52
      1.95), stable angina (1.62, 1.49-1.77), heart failure (1.56, 1.45-1.69), and non
      fatal myocardial infarction (1.54 1.42-1.67), but inversely associated with
      abdominal aortic aneurysm (0.46, 0.35-0.59) and subarachnoid haemorrhage (0.48,
      0.26-0.89). INTERPRETATION: This study suggests that associations of type 2
      diabetes vary with different incident cardiovascular diseases. These findings
      have implications for clinical risk assessment and choice of primary endpoint in
      trials on type 2 diabetes. FUNDING: Wellcome Trust, National Institute for Health
      Research, UK Medical Research Council.

PMID- 26312909
TI  - Can macrophages within the microenvironment of locally invasive rectal cancers
      predict response to radiotherapy?
AB  - BACKGROUND: Only half of patients with locally invasive rectal carcinoma respond
      to short-course preoperative radiotherapy. A predictive test enabling better
      patient selection could avoid unneccessary radiation exposure to poor responders.
      Macrophages within the tumour immune microenvironment with tumoricidal M1 and
      tumour-protective M2 phenotypes could be modulating this response. This study
      investigated the possible predictive value of M1 and M2 subpopulations in
      identifying patients' likely response to short-course preoperative radiotherapy.
      METHODS: Biopsy samples were taken from 29 patients with locally invasive rectal
      carcinoma before treatment with short-course radiotherapy and surgical specimens
      obtained after resection following short-course preoperative radiotherapy. Dual
      staining immunohistochemistry was performed with CD68 as macrophage marker, HLA
      DR as M1 marker, and CD163 as M2 marker. Samples were scored for hot-and-random
      spots by Nuance software (version 3.0.2) and compared with patients' outcome
      data. Tumour response was measured by assessment of reduction of tumour-cell
      density. FINDINGS: Samples revealing a low score for HLA-DR positive M1
      macrophages exhibited a better response to short-course radiotherapy with up to
      80% (median 80.38% [IQR 46.94-84.73]) reduction in the tumour cell density. On
      the other hand those with a high score exhibited a poor response with only up to
      20% (20.26 [0-48.19]) reduction. The difference in response between the two
      groups was significant (p=0.017). No such trends were observed for CD163+ M2
      macrophages. The ratio of HLA-DR+ to CD163+ macrophages for biopsy and resection
      samples was significantly different, showing a drop in the HLA-DR positive
      macrophages in the resection samples (p=0.024). The mean of the difference
      between the biopsy (median 2.53 [IQR 1.98-3.08]) and resection (1.38 [0.96-1.8])
      was 1.15 (p=0.024). INTERPRETATION: Patients with a variable macrophage phenotype
      composition within biopsy samples from patients with locally invasive rectal
      carcinoma respond differently to short-course preoperative radiotherapy. Further
      investigation involving a panel of macrophage and other immune-cell markers could
      verify and validate these findings and develop them as predictive tests
      identifying good responders to radiotherapy in patients with locally invasive
      rectal carcinoma. FUNDING: None.

PMID- 26312910
TI  - Effect of fluticasone propionate on virus-induced airways inflammation and anti
      viral immune responses in mice.
AB  - BACKGROUND: Inhaled corticosteroids are commonly used in the treatment of asthma
      and chronic obstructive pulmonary disease, but their effects on viral loads and
      anti-viral responses are poorly characterised. The aim of this study was to
      assess effects of inhaled fluticasone propionate on rhinovirus infection in vivo,
      in a mouse model. We tested the hypothesis that this treatment would reduce virus
      induced airways inflammation but that the effect would be confounded by
      interference with anti-viral immune responses, leading to delayed viral
      clearance. METHODS: C57BL/6 mice were intranasally dosed with fluticasone
      propionate (1 mg/kg) or vehicle (dimethyl sulfoxide, control), 1 h before
      infection with rhinovirus 1B. We assessed bronchoalveolar lavage (BAL)
      inflammatory cell numbers, and measured gene expression, protein production of
      innate mediators, or both by quantitative RT-PCR or ELISA. We compared mice
      treated with fluticasone with controls at various timepoints after infection. In
      additional experiments, recombinant interferon (IFN) beta was administered with
      fluticasone and rhinovirus 1B in both groups of mice. FINDINGS: At 24 h post
      infection, fluticasone treatment suppressed rhinovirus induction of type I and
      III IFNs in the airways (for the fluticasone-treated group compared with
      controls: mean IFNbeta BAL protein 20.2 pg/mL [SD 16.7] vs 103.0 [30.9]; mean
      IFNlambda BAL protein 102.6 pg/mL [17.4] vs 217 [44.6], p<0.001); it also
      impaired viral clearance, with increased lung tissue viral RNA copy numbers (4.7
      * 10(5) copies [SD 1.3] vs 2.6 * 10(5) [0.8], p<0.001). Despite increasing viral
      loads, fluticasone inhibited rhinovirus-induced airway inflammation as evidenced
      by suppressed BAL neutrophil numbers in fluticasone compared with control mice
      (0.021 * 10(5) [0.012] vs 0.59 * (5) [0.39], p<0.001) and by suppressed
      lymphocyte numbers (0.092 * 10(5) [0.044] vs 0.45 * 10(5) [0.11], p<0.001). By
      contrast, fluticasone increased MUC5AC proteins (158.2 arbitrary units [29.9] vs
      107.6 [7.1], p=0.0165) and MUC5B proteins (623.8 arbitrary units [231.9] vs 413.5
      [70.5], p=0.0476) in BAL at day 7 post infection. Administration of intranasal
      recombinant IFN beta (10(4) units) with fluticasone and rhinovirus 1B led to
      upregulation of interferon-inducible cytokines OAS and CXCL10/IP-10 compared with
      control mice treated with fluticasone and rhinovirus alone and improved viral
      clearance without having any effect on suppression of inflammation by
      fluticasone. INTERPRETATION: Our findings suggest that fluticasone treatment
      suppresses rhinovirus-induced airways inflammation in vivo but also impairs anti
      viral immune responses and increases viral titres, leading to mucus
      hypersecretion. Since asthma and chronic obstructive pulmonary disease are both
      associated with inherent deficient IFN responses to rhinovirus, inhaled
      corticosteroids might interact synergistically with disease to inhibit IFN and
      thus lead to increased severity of exacerbation. The clinical applicability of
      these findings requires confirmation in human models of disease. FUNDING:
      Wellcome Trust.

PMID- 26312911
TI  - The roles of DEAD box helicases in the life cycle of HIV-1.
AB  - BACKGROUND: HIV/AIDS is the largest global public health problem; about 76
      million people have been infected with HIV and 36 million people have already
      died. Existing antiviral treatment is successful but requires lifelong adherence
      and mostly targets viral factors. The virus mutates and evades both drugs and the
      human immune response. Cellular factors are potential therapeutic targets against
      HIV because the virus must conserve domains that interact with these cellular
      factors. Unlike many viruses HIV does not encode any helicases but it has been
      shown to use cellular DDX3. We screened the family of DEAD box helicases to seek
      other members as possible drug targets. METHODS: We used a robust in-house siRNA
      knockdown technique to knockdown 59 cellular helicases. We measured viral
      production and infectivity using conventional transfection and infection assays
      in HeLa-M and TZM-bl cells. To determine whether the phenotypic results that we
      found were specific to depletion of the helicases and not due to off-target
      effects, we transfected rescue plasmids for each respective helicase. FINDINGS:
      The library screen revealed five helicases that had not been previously
      identified as being associated with HIV-1 replication. We went on to study two of
      them in detail, the very closely related DDX5 and DDX17. We confirmed that
      knocking down DDX5 reduced HIV RNA and consequently viral production as measured
      by CA-p24 (capsid p24) and infectivity by two to three times compared with
      siControl-treated cells. Depletion of DDX17 reduced HIV-1 infectivity by five
      times and the extracellular (supernatant) CA-p24 by a similar reduction without
      affecting the intracellular HIV-1 Gag levels. INTERPRETATION: Our results show
      that, despite their similarity and ability to form hetero (and homo) dimers, DDX5
      and DDX17 are used by HIV in different phases of the lifecycle. DDX5 has a
      phenotype consistent with its involvement in viral transcriptional control. The
      phenotype of DDX17 knockdown suggests that it acts at a later timepoint after
      transcription. Detailed analysis of the exact processes affected by these two
      helicases is under further investigation. FUNDING: Wellcome Trust.

PMID- 26312912
TI  - Effect of UBE2L3 genotype on regulation of the linear ubiquitin chain assembly
      complex in systemic lupus erythematosus.
AB  - BACKGROUND: A single risk haplotype across UBE2L3 is strongly associated with
      systemic lupus erythematosus (SLE) and many other autoimmune diseases. UBE2L3 is
      an E2 ubiquitin-conjugating enzyme with specificity for RING-in-between-RING E3
      ligases, including HOIL-1 and HOIP, components of the linear ubiquitin chain
      assembly complex (LUBAC), which has a pivotal role in inflammation, through
      crucial regulation of NF-kappaB. We aimed to determine whether UBE2L3 regulates
      LUBAC-mediated activation of NF-kappaB, and determine the effect of UBE2L3
      genotype on NF-kappaB activation and B-cell differentiation. METHODS: UBE2L3
      genotype data from SLE genome-wide association studies was imputed by use of 1000
      Genomes data. UBE2L3 function was studied in a HEK293-NF-kappaB reporter cell
      line with standard molecular biology techniques. p65 NF-kappaB translocation in
      ex-vivo B cells and monocytes from genotyped healthy individuals was quantified
      by imaging flow cytometry. B-cell subsets from healthy individuals and patients
      with SLE, stratified by UBE2L3 genotype, were determined by multicolour flow
      cytometry. FINDINGS: rs140490, located at -270 base pairs of the UBE2L3 promoter,
      was identified as the most strongly associated single nucleotide polymorphism
      (p=8.6 * 10(-14), odds ratio 1.30, 95% CI 1.21-1.39). The rs140490 risk allele
      increased UBE2L3 expression in B cells and monocytes. Marked upregulation of NF
      kappaB was observed with combined overexpression of UBE2L3 and LUBAC, but
      abolished by dominant-negative mutant UBE2L3 (C86S), or UBE2L3 silencing. The
      rs140490 genotype correlated with basal NF-kappaB activation in ex-vivo human B
      cells and monocytes, as well as NF-kappaB sensitivity to CD40 or tumour necrosis
      factor (TNF) stimulation. UBE2L3 expression was 3-4 times higher in circulating
      plasmablasts and plasma cells than in other B-cell subsets, with higher levels in
      patients with SLE than in controls. The rs140490 genotype correlated with
      increasing plasmablast and plasma cell differentiation in patients with SLE.
      INTERPRETATION: This study shows that NF-kappaB activation mediated by LUBAC is
      exquisitely sensitive to the expression level of UBE2L3. The UBE2L3 risk
      haplotype is correlated with TNF and CD40 induced NF-kappaB activation in primary
      human cells, and with plasmablast and plasma cell expansion in SLE, consistent
      with the dependence of these cells on NF-kappaB as a survival factor. Since
      UBE2L3 is highly expressed in plasma cells, UBE2L3 could be a novel therapeutic
      target in SLE. FUNDING: Arthritis Research UK, Wellcome Trust, George Koukis
      Foundation, European Community's Seventh Framework Programme.

PMID- 26312913
TI  - A presurgical window-of-opportunity study of metformin in obesity-driven
      endometrial cancer.
AB  - BACKGROUND: Metformin use is associated with reduced cancer risk in several
      observational studies of patients with type 2 diabetes. Results from preclinical
      studies in endometrial cancer show that metformin reduces cellular proliferation
      by inhibition of the PI3K-AKT-mTOR pathway. We tested the hypothesis that
      metformin would reduce cellular proliferation in vivo in atypical endometrial
      hyperplasia and endometrial endometrioid adenocarcinoma. METHODS: We recruited
      women attending gynaecological oncology clinics in Manchester, UK, with atypical
      endometrial hyperplasia or endometrial endometrioid adenocarcinoma. Women
      received metformin (850 mg twice daily) or no drug (control) during the 1-4 week
      presurgical window between cancer diagnosis and hysterectomy according to patient
      preference. Paired blood and tumour samples were obtained at recruitment and
      hysterectomy. Cellular proliferation was assessed by Ki-67 proliferation index.
      Automated scoring on two separate occasions provided consistent replicate scores
      (SD <10%). This study is registered with the ISRCTN register, number
      ISRCTN81570194. FINDINGS: Samples from 40 women have been analysed (28 metformin
      treated [median age 64 years, IQR 58-69]; 12 control [70, 64-70]). 24 of the
      patients (60%) were obese. 22 patients (55%) had either undiagnosed diabetes
      (fasting glucose >7.0 mmol/L, n=4) or insulin resistance (homoeostatic model
      assessment of insulin resistance >2.8, n=18). Metformin was taken for a median of
      20 days (IQR 17-24), and mild gastrointestinal side-effects were reported by 22
      metformin-treated patients. In the metformin-treated group, Ki-67 was 12.9% lower
      at hysterectomy than at recruitment (95% CI 3.7-22.1, p=0.008) after adjustment
      for baseline Ki-67, Ki-67 change in controls, age, and body-mass index. No
      significant changes in phosphorylation of AKT or markers of insulin resistance
      after adjustment for treatment arm were seen. INTERPRETATION: Undiagnosed insulin
      resistance or diabetes were common in our study population. Short-term
      presurgical metformin was associated with a reduction in Ki-67 proliferation
      index. We are now exploring the hypothesis that metformin reduces Ki-67
      expression by inducing phosphorylation of AMP-activated kinase and subsequent
      mTOR proproliferative inhibition, independent of insulin and insulin-like growth
      factor receptor activation. FUNDING: Wellbeing of Women, Wellcome Trust.

PMID- 26312914
TI  - Evaluation of carotid plaque inflammation in patients with active rheumatoid
      arthritis using (18)F-fluorodeoxyglucose PET-CT and MRI: a pilot study.
AB  - BACKGROUND: Rheumatoid arthritis is associated with a 50% increased risk in
      cardiovascular mortality. Inflammation is thought to accelerate atherosclerosis
      and might also lead to an inflammatory rupture-prone plaque phenotype. We tested
      the hypothesis that patients with active rheumatoid arthritis also have carotid
      plaque inflammation and that plaque inflammation correlates with clinical and
      serological markers of inflammation. METHODS: Patients with active rheumatoid
      arthritis, defined as the Disease Activity Score in 28 joints (DAS28) score of
      more than 3.2, were recruited to a single centre study in the UK. Patients with
      carotid plaque on ultrasound underwent carotid MRI followed by (18)F
      fluorodeoxyglucose ((18)F-FDG) PET-CT. Scans were co-registered and analysed by a
      physicist, masked to clinical information. The maximum standardised uptake values
      (SUV(max)) were measured in the plaque area. The association of SUV with DAS28, C
      reactive protein, and CD4+CD28- T-cell frequency was tested with non-parametric
      statistics. Ethics approval and informed consent were obtained. FINDINGS: Scans
      were done in 13 patients, nine of whom were women. Median age was 60 years (IQR
      57-65), disease duration was 11 years (6-25), and DAS28 score was 4.52 (4.32
      5.13). None had a history or symptoms of clinical cardiovascular disease or took
      statins. All plaques caused less than 70% stenosis, and tracer uptake in plaque
      was seen on PET in all 13 patients. Median SUV(max) was 2.18 (IQR 2.00-2.65), and
      all cases had an SUV(max) greater than 1.6 (the threshold for defining carotid
      plaque inflammation). There was a significant association with SUV(max) and C
      reactive protein (r=0.58, p=0.04) and quartiles of CD4+CD28- T-cell frequency
      (p=0.045), but not with low-density lipoprotein concentrations (r=-0.49, p=0.09)
      or DAS28 score (r=0.38, p=0.20). No association was found with age (r=0.13,
      p=0.69) or sex (p=0.64). INTERPRETATION: In this small pilot study, plaque
      inflammation was seen in all patients and correlated with C-reactive protein.
      Whether this finding represents simultaneous joint and plaque inflammation, which
      might improve on treatment of joint disease, remains to be determined. CD4+CD28-
      T-cells are known to predict cardiovascular events in patients with angina. Their
      association with plaque inflammation in this study suggests a possible role in
      cardiovascular risk prediction in rheumatoid arthritis. Larger studies are
      warranted to investigate these findings further. FUNDING: North West England MRC
      Clinical Pharmacology and Therapeutics Clinical Research Fellowship, National
      Institute for Health Research, AstraZeneca-University of Manchester Strategic
      Alliance Fund.

PMID- 26312915
TI  - Role of a neurokinin B receptor antagonist in the regulation of ovarian function
      in healthy women.
AB  - BACKGROUND: Patients with loss-of-function mutation in neurokinin B (NKB) and its
      receptor show hypogonadotropic hypogonadism characterised by failure to progress
      through puberty, indicating the involvement of this newly described hypothalamic
      peptide in human reproduction. However the role of NKB in regulating ovarian
      function in adult women is unknown. We tested the hypothesis that a NKB
      antagonist would decrease gonadotropin secretion and inhibit folliculogenesis in
      healthy women. METHODS: Six healthy women with regular menstrual cycles were
      administered the NKB antagonist AZD4901 (AstraZeneca, London, UK) 40 mg orally
      twice daily for 5 days from cycle days 4-5. Transvaginal ultrasonography was
      performed at the end of drug administration, and serum gonadotropins and
      oestradiol measured. Cycle-day-matched results were compared with seven women who
      received no treatment (controls). The study received ethics committee approval,
      and all women gave written informed consent. FINDINGS: The diameter of the
      largest follicle was significantly smaller in women treated with NKB antagonist
      than in controls (mean 8.8 mm [SD 1.2] vs 11.9 [2.1], p=0.01). Serum oestradiol
      concentrations were also significantly reduced in the NKB antagonist group (mean
      112.7 pmol/L [SD 56.0] vs 240.1 [73.6], p=0.005): in keeping with this finding
      endometrial thickness was also reduced (mean 3.5 mm [SD 0.5] vs 6.4 [3.2],
      p=0.05). Concentrations of luteinising hormone were not significantly altered
      after 5 days of NKB antagonist (mean pretreatment luteinising hormone 5.2 IU/L
      [SD 2.1] vs post-treatment 6.7 [3.8], p=0.2) or when compared with control women
      (6.0 [2.4], p=0.7). One woman had minimal vaginal bleeding; there were no adverse
      events. INTERPRETATION: We have shown for the first time, to our knowledge, that
      NKB antagonist is a potent suppressor of follicle development and oestradiol
      secretion in women. This effect is likely to be mediated by reduced secretion of
      gonadotropin-releasing hormone and our results support the involvement of NKB in
      the control of human reproduction: further analysis will explore in detail
      effects on secretion of follicle-stimulating hormone and luteinising hormone. Our
      findings have potential for translational application, for example in
      endometriosis and contraception. FUNDING: Wellcome Trust through the Scottish
      Translational and Therapeutics Initiative.

PMID- 26312916
TI  - The changing demographics of inpatient hospice death: population-based, cross
      sectional study in England, 1993-2012.
AB  - BACKGROUND: The provision of good quality and equitable end-of-life care is high
      on the public and political agenda. Hospice is second only to home in terms of
      preference for place of death and scores higher than any other setting for
      quality of care. However, hospices have been criticised for inequality of access
      with respect to age, diagnosis, and socioeconomic status. We aimed to describe
      the demographic characteristics associated with hospice death in England, and
      assessed how these characteristics have changed over time. METHODS: In this
      population-based study (part of the GUIDE_Care project), we included all adults
      older than 25 years who had died in inpatient hospices in England from 1993 to
      2002. We compared deaths in 1998-2002, 2003-07, and 2008-12, with those in 1993
      97 using multivariable Poisson regression. Explanatory variables included
      individual factors (age, sex, marital status, underlying cause of death) and
      measures of deprivation based on area of residence. FINDINGS: 446 615 deaths were
      included. The annual number of hospice deaths increased from 17 440 in 1993 to 26
      032 in 2012, accounting for 3.4% of 519 313 deaths in England in 1993, and 6.0%
      of 434 105 deaths in 2012. 226 188 hospice decedents (50.6%) were men (mean age
      69.9 years, SD 12.4). The likelihood of hospice decedents being in the oldest age
      group (>85 years) increased from 1993-97 to 2008-12 (Poisson ratio 1.43, 95% CI
      1.39-1.48). Only 23 258 hospice decedents (5.2%) had non-cancer diagnoses, though
      the likelihood of non-cancer conditions increased during the same time period
      (1.41, 1.37-1.46). The likelihood of hospice decedents being resident in the
      least deprived quintile also increased (1.25, 1.22-1.29). INTERPRETATION:
      Inequalities among hospice decedents by diagnosis have decreased, although the
      absolute numbers of non-cancer diagnoses remain very small. Trends in deprivation
      are concerning, and require further exploration. FUNDING: The GUIDE_Care project
      was funded by the National Institute for Health Research (NIHR) Health Services
      and Delivery Research programme (project number 09/2000/58).

PMID- 26312917
TI  - Quantitative assessment of the cell surface proteome to identify novel
      therapeutic targets in cholangiocarcinoma.
AB  - BACKGROUND: Cholangiocarcinoma has a high mortality and morbidity. Median
      survival is less than 6 months. Surgical resection is appropriate in certain
      circumstances. Because distal cholangiocarcinoma is difficult to distinguish from
      pancreatic cancers, patients might not receive optimum therapy. Proteomics is the
      study of complex cellular proteins using mass spectrometry. The aim of this study
      was to determine the constituent proteins on the cell surface of a model of
      cholangiocarcinoma. METHODS: A sample preparation technique to enrich for cell
      surface proteins of the intrahepatic cholangiocarcinoma cell line CC-SW-1 was
      developed by modifying a NeutrAvidin-biotin system. After isolation, trypsin
      digestion, and purification, peptides were fractionated for tandem mass
      spectrometry before being analysed with the NCBInr database and the Mascot search
      algorithm. Results were confirmed by immunohistochemistry using a peroxidase
      detection technique on paraffin-embedded sections from resected specimens.
      FINDINGS: Peptide enrichment was confirmed by electrophoresis. 862 proteins were
      consistently expressed between samples (n=3). 271 of these proteins were
      attributed only to the cell surface. They included proteins used clinically for
      staging disease (cytokeratin 19 [CK19]), identifying cancer stem cells
      (epithelial cell adhesion molecule [EpCAM], neural cell adhesion molecule [NCAM],
      epithelial growth factor receptor [EGFR]), and indicating potential for
      differentiation (Frozzled receptor, Notch pathway). Novel markers from the tumour
      necrosis factor (TNF) receptor superfamily were also identified.
      Immunohistochemistry confirmed these findings. INTERPRETATION: The results from
      this surface proteomic profiling could help to identify novel therapeutic targets
      in cholangiocarcinoma. Further development of this technique could be translated
      to distinguish between distal cholangiocarcinoma and pancreatic cancers. FUNDING:
      UK Medical Research Council.

PMID- 26312918
TI  - Proteomic analysis to identify biomarkers in the primary tumour that predict
      response to neoadjuvant chemotherapy in liver metastases.
AB  - BACKGROUND: Colorectal cancer is the fourth commonest cancer in the UK, and the
      second commonest cause of cancer-related death. A knowledge of the biological
      phenotype of colorectal liver metastases would be invaluable to inform clinical
      decision making; however, deriving this information from the metastatic lesions
      is not feasible until after resection. We aimed to use proteomic analysis to
      identify biomarkers in the primary tumour that predict response to neoadjuvant
      chemotherapy in liver metastases. METHODS: Fresh tissue from both primary
      colorectal tumour and liver metastases from 17 patients was subjected to
      proteomic analysis using isobaric tagging for relative quantification. Data were
      analysed with Protein Pilot (Ab Sciex, Framingham, MA, USA), with stratification
      of patients into those showing low or high response to chemotherapy permitting
      the identification of potential predictive biomarkers. These markers were
      subsequently validated by immunohistochemistry on a tissue microarray of 63
      patients. FINDINGS: We identified 5768 discrete proteins. Five of them predicted
      histopathological response to fluorouracil-based chemotherapy regimens, of which
      the FAD binding protein NQO1 was subsequently validated by immunohistochemistry.
      When compared with the chemotherapeutic agent alone, knockdown of the
      corresponding gene with small interfering RNA decreased cell viability when co
      incubated with fluorouracil (77.1% vs 46.6%, p=0.037) and irinotecan (41.7% vs
      24.4%, p=0.006). Similar results were also seen after inhibition of protein
      activity by pretreating cells with dicoumarol. INTERPRETATION: These results show
      that proteomic sequencing of matched metastatic colorectal cancer samples is
      feasible, with high protein coverage. The high degree of similarity between the
      primary and secondary proteomes suggests that primary tissue is predictive of the
      metastatic phenotype. NQO1 expression in the primary tumour predicts response to
      neoadjuvant chemotherapy in the liver metastases, and inhibition of this protein
      at both genetic and functional levels improves chemosensitivity. FUNDING: Cancer
      Research UK.

PMID- 26312919
TI  - Unsupervised overnight closed loop insulin delivery during free living: analysis
      of randomised cross-over home studies in adults and adolescents with type 1
      diabetes.
AB  - BACKGROUND: The closed-loop system (artificial pancreas) delivers insulin in a
      glucose-responsive manner by the use of a control algorithm that automatically
      directs insulin delivery, based on real-time sensor glucose concentrations.
      Results from hospital-based studies have shown improved overnight glucose control
      and reduced risk of hypoglycaemia in type 1 diabetes. We aimed to assess whether
      unsupervised closed-loop systems can provide a realistic treatment option in
      patients with type 1 diabetes. METHODS: We combined data from two open-label,
      phase 2, randomised, cross-over, unsupervised home trials of people with type 1
      diabetes, one in 24 adults (mean age 43 years [SD 12], HbA1c 8.0% [0.9]) and the
      other in 16 adolescents (15.6 [3.6], 8.1 [0.8]). In each trial, after training on
      study devices, participants were allocated to two periods of sensor-augmented
      pump therapy either with or without overnight closed loop that used a model
      predictive control algorithm to direct insulin delivery. Allocation sequence was
      done with a computer-generated random code. Each period lasted 4 weeks in adults
      and 3 weeks in adolescents. Primary outcome for both trials was time when sensor
      glucose was in the target range (3.9-8.0 mmol/L). Analysis was by intention to
      treat. Participants (or parents) gave written informed consent. The trials are
      registered with ClinicalTrials.gov, numbers NCT01440140 and NCT01221467.
      FINDINGS: Closed loop was started by participants on their own volition on 866
      (89%) of 978 nights. The proportion of time when sensor glucose was in the target
      range between 0000 h and 0800 h was increased by a mean of 18.4% (95% CI 13.5
      23.4, p<0.0001) during closed loop compared with no closed loop. Closed loop
      significantly reduced mean overnight sensor glucose by 0.9 mmol/L (95% CI 0.4
      1.3, p=0.0001), and reduced the proportion of time when sensor glucose values
      were suggestive of hyperglycaemia (>8.0 mmol/L) (15.9%, 10.7-21.0; p<0.0001) and
      hypoglycaemia (<3.9 mmol/L) (median 0.9, IQR 0.2-2.2; p=0.014). Lower mean
      overnight glucose was associated with increased overnight insulin delivery
      (p<0.0001) without changing total daily insulin amount (p=0.84). INTERPRETATION:
      Extended use of overnight closed loop at home without supervision is feasible in
      adults and adolescents with type 1 diabetes. Clinically significant reduction in
      overnight glucose was observed accompanied by reduced time spent by patients in
      hypoglycaemia. To our knowledge, such combined effect has not been documented
      with any other means of intensified conventional insulin delivery. Longer term
      studies are warranted to assess its clinical potential. FUNDING: Diabetes UK,
      Juvenile Diabetes Research Foundation, NIHR Cambridge Biomedical Research Centre.

PMID- 26312920
TI  - Role of interleukin 33/ST2 axis in the immune-mediated pathogenesis of age
      related macular degeneration.
AB  - BACKGROUND: Age-related macular degeneration is a leading cause of irreversible
      blindness. Altered immune responses drive degeneration, in response to oxidative
      stress and hypoxia-induced regulation of metabolism. We tested the hypothesis
      that toll-like receptor activation of retinal pigment epithelium and cellular
      metabolic switch upregulate interleukin 33, which acts through its receptor ST2
      to activate both choroidal stromal fibroblasts and mast cells. By such
      mechanisms, the fibrosis and insidious degeneration, which we observe clinically,
      is accentuated. METHODS: Retinal pigment epithelial cells (ARPE-19 and B6-RPE07)
      were stimulated with toll-like receptor ligands, and energetic pathways were
      assessed through lactate production and the expression of glycolytic enzymes.
      Expression profile and secretion of interleukin 33 were determined by RT-PCR and
      western blots. Function and expression profile of bone-marrow-derived mast cells
      and human choroidal fibroblasts were also assessed. FINDINGS: The production of
      lactate, determining aerobic glycolysis, increased after stimulation of retinal
      pigment epithelial cells with LPS or poly(I:C), indicating an increase in the
      glycolytic activity after toll-like receptor stimulation. Increased levels of
      GLUT1 transcripts, and upregulation of GAPDH expression corroborated this
      finding. Furthermore, increased expression of interleukin 33 was dependent on a
      glycolytic metabolic switch and was enhanced under hypoxic conditions. ST2 was
      highly expressed in retinal pigment epithelium, choroidal mast cells, and
      choroidal fibroblasts in mouse and man. ST2+ bone-marrow-derived mast cells
      generated a spectrum of inflammatory cytokines and PGS2 when cultured with
      interleukin-33-rich retinal pigment epithelium supernatant. Interleukin-33
      treatment impaired fibroblast migration and gel contraction alongside suppression
      of MMP-2 and MMP-9 expression. INTERPRETATION: Our data highlight an unrecognised
      link between retinal pigment epithelium bioenergetic status and tissue
      remodelling of choroidal stroma. Our findings suggest that the interleukin 33/ST2
      axis and changing bioenergetic sources are potential therapeutic targets to
      inhibit progression of age-related macular degeneration. FUNDING: National
      Institute for Health Research, National Eye Research Centre.

PMID- 26312921
TI  - Effect of methotrexate on JAK/STAT pathway activation in myeloproliferative
      neoplasms.
AB  - BACKGROUND: The myeloproliferative neoplasms are a group of haematological
      malignancies characterised by pathological activation of the JAK/STAT (Janus
      kinase and signal transducer and activator of transcription) intracellular
      signalling pathway. 50-95% of patients have an acquired mutation (JAK2V617F)
      causing constitutive activation of JAK2. Our aim was to find new treatments for
      myeloproliferative neoplasms by identifying compounds that suppress JAK/STAT
      pathway activation. METHODS: We used a luciferase-based transcriptional assay in
      the low complexity Drosophila model system to screen a library of 2000 small
      molecules for modulators of JAK/STAT pathway activation. Screen hits were
      validated with western blotting in the HDLM-2 Hodgkin's lymphoma cell line. The
      HEL cell line, in which constitutive JAK/STAT pathway activation is caused by
      JAK2V617F, was used to determine the relevance of screen hits for treatment of
      myeloproliferative neoplasms. FINDINGS: Methotrexate and the chemically similar
      drug aminopterin were independently identified as strong inhibitors of the
      Drosophila JAK/STAT pathway, an effect conserved to human cells. Methotrexate did
      not affect protein phosphorylation in other intracellular signalling pathways.
      Methotrexate caused significant suppression of JAK/STAT activation in HEL cells
      at a concentration equivalent to that seen in patients taking low-dose oral
      methotrexate (p<=0.001). INTERPRETATION: Our results suggest that methotrexate is
      a promising treatment for myeloproliferative neoplasms that could be translated
      into clinical trials after assessment in primary cells. These results are
      particularly relevant in myelofibrosis. Inhibitors of JAK1/2 improve symptoms and
      prolong life in myelofibrosis, but their use is limited by cost. Other existing
      therapies for myelofibrosis appear no more effective than placebo. Methotrexate
      might bring the benefits of JAK/STAT pathway inhibition at a lower cost. FUNDING:
      Cancer Research UK, Yorkshire Cancer Research, UK Medical Research Council,
      Wellcome Trust, EU Framework Cancer Pathways.

PMID- 26312922
TI  - Eczema and indoor environment: lessons from the International Study of Asthma and
      Allergies in Childhood (ISAAC) Phase 2.
AB  - BACKGROUND: Numerous studies have reported a positive association between damp
      housing conditions and asthma, but little is known about indoor environmental
      exposures in relation to childhood eczema. We aimed to specifically investigate
      the effect of indoor mould and dampness on eczema risk in the International Study
      of Asthma and Allergies in Childhood (ISAAC). METHODS: ISAAC Phase 2 is a cross
      sectional study of 46 051 children aged 8-12 years from 20 countries. Information
      on demographics, eczema symptoms, and dampness was gathered with parental
      questionnaires. Children were examined for eczema and underwent skin prick
      testing. In a stratified subgroup, dust samples were collected to measure house
      dust mite exposure. Sex, maternal education, parental allergy, pet ownership,
      maternal smoking, having an older sibling, bedroom sharing, and cooking with
      fuels were explored as potential confounders or effect modifiers in logistic
      regression analysis. FINDINGS: Current residential exposure to dampness and mould
      was significantly associated with flexural eczema in the previous year, with a
      stronger association seen in non-affluent than in affluent countries (adjusted
      odds ratio [OR] 1.96, 95% CI 1.62-2.37, vs 1.34, 1.18-1.51). Dampness and mould
      in the first year of life was also significantly associated with parent-reported
      eczema ever (1.94, 1.40-2.68, vs 1.43, 1.28-1.60). However, the association with
      flexural eczema on examination was not significant (0.93, 0.76-1.13). Risk
      estimates were similar in children positive and negative on skin prick testing,
      and were not appreciably altered by the effect modifiers, apart from parental
      allergic disease (parental allergies OR 1.35, 95% CI 1.18-1.54, vs no parental
      allergies 1.61, 1.37-1.90). INTERPRETATION: These data suggest an association
      between damp housing conditions and childhood eczema symptoms, which may be
      causal. Further work is needed to elucidate possible mechanisms. Modification to
      home environment to reduce dampness and mould could be harnessed to improve or
      even prevent this common and debilitating condition. FUNDING: None.

PMID- 26312923
TI  - Symptomatic carotid stenosis and stroke risk in patients with transient ischemic
      attack according to the tissue-based definition.
AB  - BACKGROUND AND PURPOSE: Symptomatic carotid stenosis (sCS), a common cause of
      transient ischemic attack (TIA), is correlated with higher stroke risk. We
      investigated the frequency and associated factors of sCS in patients with TIA and
      the association between sCS and stroke risk following TIA. METHODS: Over a three
      year period (2011-2013), 861 consecutive patients with TIA, who were admitted to
      the Department of Neurology at the University of Lubeck, Germany, were included
      in a monocenter study and prospectively evaluated. Diagnosis of TIA was in
      accordance with the tissue-based definition (transient neurological symptoms
      without evidence of infarction by brain imaging). RESULTS: Of 827 patients (mean
      age, 70 +/- 13.2 years; 49.7% women), 64 patients (7.7%; 95% confidence interval
      [CI], 5.9%-9.7%) exhibited sCS and 3 patients (0.3%) showed an occlusion of the
      corresponding internal carotid artery. Logistic regression revealed that sCS was
      associated with male sex (odds ratio [OR], 2.7; 95% CI, 1.2-3.6; p = 0.012),
      amaurosis fugax (OR, 8.1; 95% CI, 3.4-19-4; p < 0.001), unilateral weakness (OR,
      3.4; 95% CI, 1.9-6.1; p < 0.001), symptom duration less than 1 h (OR, 2.0; 95%
      CI, 1.1-3.4; p = 0.019) and previous stroke (OR, 2.7; 95% CI, 1.5-4.7; p =
      0.001). During hospitalization (mean, 6.6 days), five patients (0.6%; 95% CI,
      0.1%-1.2%) suffered from stroke. The stroke risk was higher in patients with sCS
      than in those without sCS (6.3% vs. 0.1%; p < 0.001), whereas the recurrent TIA
      risk (2.6%) did not differ between the groups (4.7% vs. 2.5%; p = 0.29).
      CONCLUSION: SCS appears to be associated with a higher risk of stroke in patients
      with TIA defined according to the tissue-based definition.

PMID- 26312924
TI  - Chagas disease: still a challenge around the world.

PMID- 26312925
TI  - Theranostic applications of phage display to control leishmaniasis: selection of
      biomarkers for serodiagnostics, vaccination, and immunotherapy.
AB  - Phage display is a high-throughput subtractive proteomic technology used for the
      generation and screening of large peptide and antibody libraries. It is based on
      the selection of phage-fused surface-exposed peptides that recognize specific
      ligands and demonstrate desired functionality for diagnostic and therapeutic
      purposes. Phage display has provided unmatched tools for controlling viral,
      bacterial, fungal, and parasitic infections, and allowed identification of new
      therapeutic targets to treat cancer, metabolic diseases, and other chronic
      conditions. This review presents recent advancements in serodiagnostics and
      prevention of leishmaniasis -an important tropical parasitic disease- achieved
      using phage display for the identification of novel antigens with improved
      sensitivity and specificity. Our focus is on theranostics of visceral
      leishmaniasis with the aim to develop biomarker candidates exhibiting both
      diagnostic and therapeutic potential to fight this important, yet neglected,
      tropical disease. 

PMID- 26312926
TI  - History of insecticide resistance of Triatominae vectors.
AB  - In the last 15 years, different types of Triatominae resistance to different
      insecticides have been reported; thus, resistance may be more widespread than
      known, requiring better characterization and delimitation, which was the aim of
      this review. This review was structured on a literature search of all articles
      from 1970 to 2015 in the PubMed database that contained the keywords Insecticide
      resistance and Triatominae . Out of 295 articles screened by title, 33 texts were
      selected for detailed analysis. Insecticide resistance of Triatomines is a
      complex phenomenon that has been primarily reported in Argentina and Bolivia, and
      is caused by different factors (associated or isolated). Insecticide resistance
      of Triatominae is a characteristic inherited in an autosomal and semi-dominant
      manner, and is polygenic, being present in both domestic and sylvatic
      populations. The toxicological profile observed in eggs cannot be transposed to
      different stages of evolution. Different toxicological profiles exist at macro-
      and microgeographical levels. The insecticide phenotype has both reproductive and
      developmental costs. Different physiological mechanisms are involved in
      resistance. Studies of Triatomine resistance to insecticides highlight three
      deficiencies in interpreting the obtained results: I) the vast diversity of
      methodologies, despite the existence of a single guiding protocol; II) the lack
      of information on the actual impact of resistance ratios in the field; and III)
      the concept of the susceptibility reference lineage. Research on the biological
      and behavioral characteristics of each Triatominae species that has evolved
      resistance is required in relation to the environmental conditions of each
      region. 

PMID- 26312927
TI  - Prevalence of neurocognitive disorders and depression in a Brazilian HIV
      population.
AB  - INTRODUCTION: Combined antiretroviral therapy has enabled human immunodeficiency
      virus (HIV) carriers to live longer. This increased life expectancy is associated
      with the occurrence of degenerative diseases, including HIV-associated
      neurocognitive disorders (HAND), which are diagnosed via a complex
      neuropsychological assessment. The International HIV Dementia Scale (IHDS) is a
      screening instrument validated in Brazil for use in the absence of
      neuropsychological evaluation. HIV patients are frequently diagnosed with
      depression. We aimed to determine the prevalence of neurocognitive impairment
      using the IHDS and depressive disorders using the Hamilton Rating Scale for
      Depression (HAM-D17), compare the IHDS performance with the performances on the
      Timed Gait Test (TGT), the Digit Symbol Coding Test (DS) and the Brazilian
      version of the Scale of Instrumental Activities of Daily Living (IADL), and
      evaluate the association between the IHDS performance and clinical-demographic
      variables. METHODS: One hundred fourteen patients were evaluated in a cross
      sectional study conducted in a public outpatient clinic for infectious diseases
      in Marilia City, State of Sao Paulo, Brazil. Data were collected following
      consultation. Statistical analysis was performed in accordance with the nature
      and distribution of the data and hypotheses. RESULTS: According to the IHDS,
      53.2% of the sampled patients were neuropsychologically impaired. According to
      the HAM-D17, 26.3% had depressive disorders. There were significant associations
      between the IHDS and the TGT and DS. Multiple regression analysis indicated that
      female gender, educational level, and cluster of differentiation 4 (CD4) levels
      were significantly and independently associated with neurocognitive impairment.
      CONCLUSIONS: The prevalence of neurocognitive impairment according to the IHDS is
      high and associated with female gender, education level, and low CD4 levels.

PMID- 26312928
TI  - Trends and factors associated with dengue mortality and fatality in Brazil.
AB  - INTRODUCTION: Studies that generate information that may reduce the dengue death
      risk are essential. This study analyzed time trends and risk factors for dengue
      mortality and fatality in Brazil from 2001 to 2011. METHODS: Time trends for
      dengue mortality and fatality rates were analyzed using simple linear regression.
      Associations between the dengue mortality and the case fatality rates and
      socioeconomic, demographic, and health care indicators at the municipality level
      were analyzed using negative binomial regression. RESULTS: The dengue hemorrhagic
      fever case fatality rate increased in Brazil from 2001 to 2011 (beta=0.67;
      p=0.036), in patients aged 0-14 years (beta=0.48; p=0.030) and in those aged >=15
      years (beta=1.1; p<0.01). Factors associated with the dengue case fatality rate
      were the average income per capita (MRR=0.99; p=0.038) and the number of basic
      health units per population (MRR=0.89; p<0.001). Mortality rates increased from
      2001 to 2011 (beta=0.350; p=0.002).Factors associated with mortality were
      inequality (RR=1.02; p=0.001) high income per capita (MRR=0.99; p=0.005), and
      higher proportions of populations living in urban areas (MRR=1.01; p<0.001).
      CONCLUSIONS: The increases in the dengue mortality and case fatality rates and
      the associated socioeconomic and health care factors, suggest the need for
      structural and intersectoral investments to improve living conditions and to
      sustainably reduce these outcomes.

PMID- 26312929
TI  - The absence of the human platelet antigen polymorphism effect on fibrosis
      progression in human immunodeficiency virus-1/hepatitis C virus coinfected
      patients.
AB  - INTRODUCTION: Hepatic fibrosis progression in patients with chronic hepatitis C
      virus infections has been associated with viral and host factors, including
      genetic polymorphisms. Human platelet antigen polymorphisms are associated with
      the rapid development of fibrosis in HCV-monoinfected patients. This study aimed
      to determine whether such an association exists in human immunodeficiency virus
      1/hepatitis C virus-coinfected patients. METHODS: Genomic deoxyribonucleic acid
      from 36 human immunodeficiency virus-1/hepatitis C virus-coinfected patients was
      genotyped to determine the presence of human platelet antigens-1, -3, or -5
      polymorphisms. Fibrosis progression was evaluated using the Metavir scoring
      system, and the patients were assigned to two groups, namely, G1 that comprised
      patients with F1, portal fibrosis without septa, or F2, few septa (n = 23) and G2
      that comprised patients with F3, numerous septa, or F4, cirrhosis (n = 13).
      Fisher's exact test was utilized to determine possible associations between the
      human platelet antigen polymorphisms and fibrosis progression. RESULTS: There
      were no deviations from the Hardy-Weinberg equilibrium in the human platelet
      antigen systems evaluated. Statistically significant differences were not
      observed between G1 and G2 with respect to the distributions of the allelic and
      genotypic frequencies of the human platelet antigen systems. CONCLUSION: The
      greater stimulation of hepatic stellate cells by the human immunodeficiency virus
      and, consequently, the increased expression of transforming growth factor beta
      can offset the effect of human platelet antigen polymorphism on the progression
      of fibrosis in patients coinfected with the human immunodeficiency virus-1 and
      the hepatitis C virus.

PMID- 26312930
TI  - Detection of immunogenic proteins from Anopheles sundaicus salivary glands in the
      human serum.
AB  - INTRODUCTION: The saliva of mosquitoes has an important role in the transmission
      of several diseases, including malaria, and contains substances with
      vasomodulating and immunomodulating effects to counteract the host physiological
      mechanisms and enhance pathogen transmission. As immunomodulatory components,
      salivary gland proteins can induce the generation of specific IgG antibodies in
      the host, which can be used as specific biomarkers of exposure to Anopheles
      sundaicus . The objective of this study was to identify immunogenic proteins from
      the salivary glands of Anopheles sundaicus by reaction with sera from individuals
      living in malaria-endemic areas who are thus exposed to Anopheles mosquitoes.
      METHODS: IgG antibodies targeting salivary gland proteins in serum samples from
      individuals living in malaria-endemic areas were measured by enzyme-linked
      immunosorbent assay (ELISA). Sera from healthy individuals living in non-endemic
      areas were used as negative controls. Determination of the presence of salivary
      gland immunogenic proteins was carried out by western blotting. RESULTS: Sixteen
      bands appeared in sodium dodecyl sulfate polyacrylamide gel electrophoresis, with
      molecule weights ranging from 22 to 144kDa. Among the exposed individuals, IgG
      responses to salivary gland proteins were variable. Protein bands with molecular
      weights of 46, 41, 33, and 31kDa were the most immunogenic. These immunogenic
      proteins were consistently recognized by pooled serum and individual samples from
      people living in malaria-endemic areas but not by negative controls. CONCLUSIONS:
      These results support the potential use of immunogenic proteins from the salivary
      glands of Anopheles as candidate markers of bite exposure or in malaria vaccines.

PMID- 26312931
TI  - Variability of susceptibility to deltamethrin in peridomestic Triatoma sordida
      from Triangulo Mineiro, State of Minas Gerais, Brazil.
AB  - INTRODUCTION: Despite chemical and physical vector control strategies, persistent
      infestations of Triatoma sordida have been reported in a large part of Minas
      Gerais, Brazil, and the cause for this is little investigated. We aimed to
      characterize the deltamethrin toxicological profile in peridomestic T.
      sordidapopulations from Triangulo Mineiro area of Minas Gerais. METHODS:
      Susceptibility to deltamethrin was assessed in seventeen peridomestic T. sordida
      populations. Serial dilutions of deltamethrin in acetone (0.2uL) were topically
      applied on the first instar nymphs (F1; five days old; fasting weight, 1.2 +/-
      0.2mg). Dose response results were analyzed using Probit software, and the lethal
      doses, slope and resistance ratios were determined. Qualitative tests were also
      performed. RESULTS: The deltamethrin susceptibility profile of T. sordida
      populations revealed resistance ratios ranging from 0.84 to 2.8. The percentage
      mortality in response to a diagnostic dose was 100.0% in all populations.
      CONCLUSIONS: From our results, the lack of resistance to insecticides but
      persistent T. sordida infestations in the Triangulo Mineiro area may be because
      of: 1) environmental degradation facilitating dispersion of T. sordida, allowing
      colonization in artificial ecotopes; 2) operational failures; and 3) complexity
      of the peridomicile in the study area.These variables are being investigated.

PMID- 26312932
TI  - Susceptibility of Triatoma sordida Stal, 1859 (Hemiptera: Reduviidae) to alpha
      cypermethrin under natural climatic conditions.
AB  - INTRODUCTION: Despite the recommendations by interpretation of resistance ratios
      obtained in laboratory bioassays, little is known about the actual impact of
      these results in the effectiveness of vector control activities in the field. In
      this context, our objective was to determine the mean value of different
      resistance ratios obtained by laboratory bioassays performed as part of the
      chemical control strategies of Triatoma sordida in the field. METHODS: Field
      bioassays were developed in Monte Azul and Coracao de Jesus (Southeast, Brazil).
      In each location, samples were formed with three domestic units treated with
      alpha-cypermethrin 20.0% (Alfatek (r) 200 SC). One day after spraying, 10 fifth
      instar nymphs remained in contact with the surfaces treated (adobe with plaster,
      adobe without plaster, or wood) with insecticide in plastic cones for 72h. Three
      cones were exposed inside the intradomicile and the peridomicile. The insects in
      the control group were exposed to an insecticide-free piece of cardboard.
      Mortality was measured 72h after removal of the insects from the treated
      surfaces. The tests were realized in triplicate. RESULTS: Mortality was 100.0% in
      all locations, except for Monte Azul; Landinho (96.6%) and Coracao de Jesus;
      Barriguda (96.6%). CONCLUSIONS: Although the resistant populations in laboratory
      tests proved to be susceptible in the field, this observation is not sufficient
      to suggest that the cut-off points used to justify the resistance ratio should be
      changed. In this sense, we recommend that laboratory and field bioassays are
      carried out with a greater number of Triatominae populations to allow more in
      depth consideration of the subject.

PMID- 26312933
TI  - Preliminary screening of the larvicidal effect of Brevibacillus laterosporus
      strains against the blowfly Chrysomya megacephala (Fabricius, 1794) (Diptera:
      Calliphoridae).
AB  - INTRODUCTION: This study evaluated whether different strains of Brevibacillus
      laterosporus could be used to control larvae of the blowfly Chrysomya
      megacephala, a pest that affects both human and animal health. METHODS: Mortality
      rates were recorded after 1-mL suspensions of sporulated cells of 14 different
      strains of B. laterosporus were added to 2.5g of premixed diet consisting of
      rotting ground beef fed to first instar larvae of C. megacephala. All bioassays
      were performed using 10 larvae per strain, with a minimum of three replicates for
      each bioassay. Larval mortality was recorded daily up to seven days. RESULTS:
      Strains Bon 707, IGM 16-92, and Shi 3 showed the highest toxicity toward the
      larvae producing 70.5%, 64.5%, and 51.6% of larval mortality, respectively, which
      was significantly higher than that in the control group (p < 0.05). In contrast,
      strains NRS 1642, NRS 661, NRS 590 BL 856, NRS 342, ATCC 6457, Bon 712, and NRS
      1247 showed limited or no pathogenic activity against the target larvae.
      CONCLUSIONS: Our preliminary data indicated that B. laterosporus could be used to
      develop bioinsecticides against C. megacephala.

PMID- 26312934
TI  - Antibacterial, anti-swarming and anti-biofilm formation activities of Chamaemelum
      nobile against Pseudomonas aeruginosa.
AB  - INTRODUCTION: Chamomile (Chamaemelum nobile) is widely used throughout the world,
      and has anti-inflammatory, deodorant, bacteriostatic, antimicrobial, carminative,
      sedative, antiseptic, anti-catarrhal, and spasmolytic properties. Because of the
      increasing incidence of drug-resistant bacteria, the development of natural
      antibacterial sources such as medical herbs for the treatment of infectious
      diseases is necessary. Extracts from different plant parts such as the leaves,
      flowers, fruit, and bark of Combretum albiflorum, Laurus nobilis , and Sonchus
      oleraceus were found to possess anti-quorum sensing (QS) activities. In this
      study, we evaluated the effect of C. nobile against Pseudomonas aeruginosa
      biofilm formation. METHODS: The P. aeruginosa samples were isolated from patients
      with different types of infection, including wound infection, septicemia, and
      urinary tract infection. The flowers of C. nobile were dried and the extract was
      removed using a rotary device and then dissolved in dimethyl sulfoxide at pH 7.4.
      The microdilution method was used to evaluate the minimum inhibitory
      concentration (MIC) of this extract on P. aeruginosa , and biofilm inhibition was
      assayed. RESULTS: Eighty percent of the isolated samples (16/20) could form a
      biofilm, and most of these were isolated from wound infections. The biofilm
      inhibitory concentration of the C. nobile extract was 6.25-25mg/ml, whereas the
      MIC was 12.5-50mg/ml. CONCLUSIONS: The anti-QS property of C. nobile may play an
      important role in its antibacterial activity, thus offering an additional
      strategy in the fight against bacterial infections. However, molecular
      investigation is required to explore the exact mechanisms of the antibacterial
      action and functions of this phytocompound.

PMID- 26312935
TI  - Evaluation of the reference value for the Montenegro skin test.
AB  - INTRODUCTION: The Montenegro skin test (MST) has good clinical applicability and
      low cost for the diagnosis of American tegumentary leishmaniasis (ATL). However,
      no studies have validated the reference value (5mm) typically used to
      discriminate positive and negative results. We investigated MST results and
      evaluated its performance using different cut-off points. METHODS: The results of
      laboratory tests for 4,256 patients with suspected ATL were analyzed, and 1,182
      individuals were found to fulfill the established criteria. Two groups were
      formed. The positive cutaneous leishmaniasis (PCL) group included patients with
      skin lesions and positive direct search for parasites (DS) results. The negative
      cutaneous leishmaniasis (NCL) group included patients with skin lesions with
      evolution up to 2 months, negative DS results, and negative indirect
      immunofluorescence assay results who were residents of urban areas that were
      reported to be probable sites of infection at domiciles and peridomiciles.
      RESULTS: The PCL and NCL groups included 769 and 413 individuals, respectively.
      The mean +/- standard deviation MST in the PCL group was 12.62 +/- 5.91mm [95%
      confidence interval (CI): 12.20-13.04], and that in the NCL group was 1.43 +/-
      2.17mm (95% CI: 1.23-1.63). Receiver-operating characteristic curve analysis
      indicated 97.4% sensitivity and 93.9% specificity for a cut-off of 5mm and 95.8%
      sensitivity and 97.1% specificity for a cut-off of 6mm. CONCLUSIONS: Either 5mm
      or 6mm could be used as the cut-off value for diagnosing ATL, as both values had
      high sensitivity and specificity.

PMID- 26312936
TI  - Efficacy and tolerability of two single-day regimens of triclabendazole for
      fascioliasis in Peruvian children.
AB  - INTRODUCTION: The therapeutic scheme of triclabendazole (TCBZ), the recommended
      anthelmintic against Fasciola hepatica , involves 10mg/kg of body weight
      administered in a single dose; however, clinical trials in children are scarce.
      We evaluated the efficacy and tolerability of 2 schemes of TCBZ. METHODS: Eighty
      four Peruvian children with F. hepatica eggs in their stools were allocated into
      2 groups: 44 received 2 dosages of 7.5mg/kg each with a 12-h interval (Group I),
      and 40 received a single 10-mg/kg dose (Group II). Evaluation of efficacy was
      based on the presence of eggs in stools, and tolerability was based on the
      presence of symptoms and signs post-treatment. RESULTS: A parasitological cure
      was obtained in 100% of individuals from Group I and 95% of individuals from
      Group II. The most common adverse event was biliary colic. CONCLUSIONS: The
      tested scheme was efficacious and tolerable, and it might be an optimal scheme in
      the region. To the best of our knowledge, this represents the largest series of
      children treated with TCBZ in a non-hospital setting.

PMID- 26312937
TI  - Molecular identification and antifungal susceptibility profiles of Candida
      parapsilosis complex species isolated from culture collection of clinical
      samples.
AB  - INTRODUCTION: Candida parapsilosis is a common yeast species found in cases of
      onychomycosis and candidemia associated with infected intravascular devices. In
      this study, we differentiated Candida parapsilosis sensu stricto, Candida
      orthopsilosis , and Candida metapsilosis from a culture collection containing
      blood and subungual scraping samples. Furthermore, we assessed the in vitro
      antifungal susceptibility of these species to fluconazole, itraconazole,
      voriconazole, posaconazole, amphotericin B, and caspofungin. METHODS:
      Differentiation of C. parapsilosis complex species was performed by amplification
      of the secondary alcohol dehydrogenase (SADH) gene and digestion by the
      restriction enzyme Ban I. All isolates were evaluated for the determination of
      minimal inhibitory concentrations using Etest, a method for antifungal
      susceptibility testing. RESULTS: Among the 87 isolates, 78 (89.7%) were
      identified as C. parapsilosis sensu stricto , five (5.7%) were identified as C.
      orthopsilosis , and four (4.6%) were identified as C. metapsilosis . Analysis of
      antifungal susceptibility showed that C. parapsilosis sensu strictoisolates were
      less susceptible to amphotericin B and itraconazole. One C. parapsilosis sensu
      stricto isolate was resistant to amphotericin B and itraconazole. Moreover, 10.2%
      of C. parapsilosis sensu stricto isolates were resistant to caspofungin. Two C.
      parapsilosis sensu strictoisolates and one C. metapsilosis isolate were
      susceptible to fluconazole in a dose-dependent manner. CONCLUSIONS: We reported
      the first molecular identification of C. parapsilosiscomplex species in State of
      Goias, Brazil. Additionally, we showed that although the three species exhibited
      differences in antifungal susceptibility profiles, the primary susceptibility of
      this species was to caspofungin.

PMID- 26312938
TI  - Injuries caused by aquatic animals in Brazil: an analysis of the data present in
      the information system for notifiable diseases.
AB  - INTRODUCTION: We present a review of injuries in humans caused by aquatic animals
      in Brazil using the Information System for Notifiable Diseases [ Sistema de
      Informacao de Agravos de Notificacao (SINAN)] database. METHODS: A descriptive
      and retrospective epidemiological study was conducted from 2007 to 2013. RESULTS:
      A total of 4,118 accidents were recorded. Of these accidents, 88.7% (3,651) were
      caused by venomous species, and 11.3% (467) were caused by poisonous, traumatic
      or unidentified aquatic animals. Most of the events were injuries by stingrays
      (69%) and jellyfish (13.1%). The North region was responsible for the majority of
      reports (66.2%), with a significant emphasis on accidents caused by freshwater
      stingrays (92.2% or 2,317 cases). In the South region, the region with the second
      highest number of records (15.7%), jellyfish caused the majority of accidents
      (83.7% or 452 cases). The Northeastern region, with 12.5% of the records, was
      notable because almost all accidents were caused by toadfish (95.6% or 174
      cases). CONCLUSIONS: Although a comparison of different databases has not been
      performed, the data presented in this study, compared to local and regional
      surveys, raises the hypothesis of underreporting of accidents. As the SINAN is
      the official system for the notification of accidents by venomous animals in
      Brazil, it is imperative that its operation be reviewed and improved, given that
      effective measures to prevent accidents by venomous animals depend on a reliable
      database and the ability to accurately report the true conditions.

PMID- 26312939
TI  - Impact of livestock on a mosquito community (Diptera: Culicidae) in a Brazilian
      tropical dry forest.
AB  - INTRODUCTION: This study evaluated the effects of cattle removal on the Culicidae
      mosquito community structure in a tropical dry forest in Brazil. METHODS:
      Culicidae were collected during dry and wet seasons in cattle presence and
      absence between August 2008 and October 2010 and assessed using multivariate
      statistical models. RESULTS: Cattle removal did not significantly alter Culicidae
      species richness and abundance. However, alterations were noted in Culicidae
      community composition. CONCLUSIONS: This is the first study to evaluate the
      impact of cattle removal on Culicidae community structure in Brazil and
      demonstrates the importance of assessing ecological parameters such as community
      species composition.

PMID- 26312940
TI  - Phenotypic and molecular characterization of CTX-M extended-spectrum beta
      lactamase-producing Escherichia coli isolates in Shiraz, Iran.
AB  - INTRODUCTION: The aim of this study was to detect the prevalence of the extended
      spectrum beta-lactamase (ESBL)-encoding CTX-M gene in Escherichia coliisolates.
      METHODS: Phenotypic screening of 376 E. coli isolates for ESBL was conducted
      using disk diffusion. ESBL-producing isolates were tested using PCR and specific
      primers. The bla(CTX-M) cluster was identified using the RFLP method, and its
      genotype was sequenced. RESULTS: From 202 ESBL-producing E. coli , 185 (91.5%)
      possessed CTX-M genes. CTX-M-1 subtypes were found in 98% of the isolates. The
      bla(CTX-M) gene was identical to CTX-M-15. CONCLUSIONS: A high prevalence of CTX
      M-1-producing E. coli apparently exists in Shiraz, Iran.

PMID- 26312941
TI  - New strategies for active finding of leprosy cases in the Amazonian region.
AB  - INTRODUCTION: The use of the Self-Image Form (SIF) expands the identification of
      active leprosy cases to neighbors of index cases. METHODS: The SIF was used to
      screen two groups: case (neighbors of index cases of leprosy) and control
      (individuals residing next to houses without leprosy) group. A specialist
      investigated suspected leprosy cases for disease confirmation. RESULTS: New cases
      of leprosy were diagnosed in the case group (n = 7, 8.6%), but not the control
      group. CONCLUSIONS: The new surveillance strategy is inexpensive, efficient, and
      feasible within a primary health strategy. Future studies can help improve the
      use of the SIF.

PMID- 26312942
TI  - Acute disseminated encephalomyelitis following inactivated influenza vaccination
      in the Brazilian Amazon: a case report.
AB  - Here, we describe a case of acute disseminated encephalomyelitis (ADEM) that
      occurred during a plausible risk interval following inactivated influenza
      vaccination in a previously healthy 27-year-old man from Manaus, Brazil. He was
      treated with intravenous methylprednisolone and immunoglobulin. One-month follow
      up revealed resolution of the brain lesions, but not of the spinal cord lesions.
      No recurrence or progression of the main neurological symptoms was observed.
      After two years of monitoring, the patient continues to experience weak lower
      limbs and urinary retention. Thus, we recommend that ADEM should be considered in
      a patient presenting with neurological symptoms after influenza vaccination. 

PMID- 26312943
TI  - Testicular schistosomiasis as differential diagnosis for testicular nodules: a
      case report.
AB  - Despite its infrequent occurrence, testicular schistosomiasis forming pseudo
      tumors can be considered in the differential diagnosis of testicular tumors,
      especially in areas where the parasitic disease is endemic. In this report, we
      present a case of testicular schistosomiasis caused by Schistosoma mansoni and
      mimicking a testicular neoplasm. We describe the patterns of a testicular nodule
      on ultrasonography and magnetic resonance images in a 46-year-old man. The nodule
      was removed after a pre-operative diagnosis of a non-malignant lesion. Histology
      demonstrated granulomas with epithelioid macrophages and eosinophils around S.
      mansoni eggs within a fibrous tissue that formed a nodular structure. 

PMID- 26312944
TI  - Hypersensitivity reaction to Sporothrix schenckii: erythema nodosum associated
      with sporotrichosis.

PMID- 26312945
TI  - Laparoscopic Diaphragmatic Hemiplication in Children with Acquired Diaphragmatic
      Eventration After Congenital Heart Surgery.
AB  - PURPOSE: To report our technique and experiences in the laparoscopic
      diaphragmatic hemiplication (LDHP) in children with acquired diaphragmatic
      eventration after congenital heart surgery. SUBJECTS AND METHODS: Between October
      2007 to December 2013, 3498 children with congenital heart disease underwent
      cardiac surgery in our hospital, and 40 (1.14%) of them had unilateral
      diaphragmatic elevation on postoperative chest X-ray (mean elevation, 2.5 +/-
      0.26 intercostal spaces [ICS]) and were diagnosed as having diaphragmatic
      eventration due to diaphragmatic hemiparesis as a result of phrenic nerve injury.
      These 40 patients were followed up, and 22 of them recovered after conservative
      treatment; the other 18 needed surgical intervention. We conducted a
      retrospective study relating to surgical indications, surgical technique,
      complications, and outcomes. RESULTS: There were 24 boys and 16 girls with a mean
      age of 10.0 +/- 4.5 months old (range, 2 months-4 years). Twenty-two patients did
      not require surgical intervention. Eighteen patients underwent LDHP (12 cases
      left-sided and 6 cases right-sided); 2 of them had emergency LDHP with a history
      of ventilator dependency after cardiac surgery, and 16 of them had planned LDHP
      with a history of recurrent pneumonia and dyspnea. The operative time was 60 +/-
      7.9 minutes (range, 45-105 minutes), with minimal blood loss (3 +/- 1.5 mL
      [range, 1-9 mL]), no intra- or postoperative complications, and postoperative
      hospital stay of 7 +/- 1.3 days (range, 5-10 days). The diaphragmatic drop was
      2.4 +/- 0.2 (range, 2-4 ICS) without recurrence, and the follow-up time for all
      40 patients was 14.8 +/- 1.6 months (range, 11-36 months). CONCLUSIONS: Our study
      further shows that LDHP is feasible and effective in selected patients after
      congenital heart surgery. Our technique is convenient and provides excellent
      clinical and radiological results.

PMID- 26312946
TI  - Access to the carotid artery bifurcation: Cadaveric study with application to
      nasotracheal intubation as a technique to improve access to a high carotid artery
      bifurcation.
AB  - Carotid endarterectomy (CEA) is a common and efficacious surgical procedure for
      the prevention of ischemic stroke due to atherosclerosis of the internal carotid
      artery (ICA). A high common carotid artery bifurcation can make CEA technically
      difficult due to limited carotid artery exposure. A cadaveric study was performed
      to evaluate the efficacy of nasotracheal intubation for improving access to a
      high carotid artery bifurcation. Based on this study, nasotracheal intubation
      does not improve access to a high carotid artery bifurcation as compared with
      orotracheal intubation. 

PMID- 26312948
TI  - Bringing diagnostics to developing countries: an interview with Rosanna Peeling.
AB  - Interview with Professor Rosanna Peeling, PhD by Claire Raison (Commissioning
      Editor) Professor Rosanna Peeling is Chair of Diagnostic Research at the London
      School of Hygiene and Tropical Medicine (London, UK) and founded the
      International Diagnostics Centre at the institution. Professor Peeling previously
      worked for the WHO in Geneva, Switzerland, and continues to work on innovations
      for molecular diagnostics for point-of-care use in developing countries,
      addressing challenges posed by lack of funding and resources, regulatory issues
      and under-developed healthcare systems in these locations. Here, she discusses
      her career, recent progress in the field and how connectivity will affect global
      healthcare. 

PMID- 26312947
TI  - Coadministration of cruzipain and GM-CSF DNAs, a new immunotherapeutic vaccine
      against Trypanosoma cruzi infection.
AB  - Therapeutic vaccine research and development are especially important in Chagas
      disease considering the characteristics of the chronic infection and the number
      of people in the Americas living with a parasite infection for decades. We have
      previously reported the efficacy of attenuated Salmonella enterica (S) carrying
      plasmid encoding cruzipain (SCz) to protect against Trypanosoma cruzi infection.
      In the present work we investigated whether Cz DNA vaccine immunotherapy could be
      effective in controlling an ongoing T. cruzi infection in mice. We here report
      the intramuscular administration of naked Cz DNA or the oral administration of
      Salmonella as Cz DNA delivery system as therapeutic vaccines in mice during acute
      or chronic infection. The coadministration of a plasmid encoding GM-CSF improved
      vaccine performance, indicating that the stimulation of innate immune cells is
      needed in the event of an ongoing infection. These therapeutic vaccines were able
      to address the response to a protective and sustained Th1 biased profile not only
      against Cz but also against a variety of parasite antigens. The combined
      therapeutic vaccine during the chronic phase of infection prevents tissue
      pathology as shown by a reduced level of enzyme activity characteristic of tissue
      damage and a tissue status compatible with normal tissue. The obtained results
      suggest that immunotherapy with Cz and GM-CSF DNAs, either alone or in
      combination with other drug treatments, may represent a promising alternative for
      Chagas disease therapy. 

PMID- 26312949
TI  - Anti-signal recognition particle antibody in patients without inflammatory
      myopathy: a survey of 6180 patients with connective tissue diseases.
AB  - OBJECTIVES: To clarify the prevalence of anti-signal recognition particle (anti
      SRP) antibody in connective tissue diseases (CTDs) and investigate the clinical
      characteristics of patients without inflammatory myopathy. METHOD: Sera from 6180
      patients with CTD were examined by immunoprecipitation (IPP) assays, and the
      records of patients positive for anti-SRP antibody were reviewed retrospectively.
      The antibody against the 54-kDa protein of SRP (SRP54) was quantified by enzyme
      linked immunosorbent assay (ELISA) in patients with anti-SRP antibody. RESULTS:
      Of the 28 patients positive for anti-SRP antibody, nine (32.1%) did not have
      inflammatory myopathy. The clinical diagnoses and characteristics of those
      patients varied considerably. In patients with inflammatory myopathy, the index
      of anti-SRP54 was much higher than in those without myopathy (1.15 vs. 0.46; p =
      0.036). CONCLUSIONS: The prevalence of anti-SRP antibody was 0.5% in a cohort of
      Japanese patients with CTD, and one-third of them did not have inflammatory
      myopathy. Sera from patients with inflammatory myopathy recognized SRP54 more
      strongly than in those without myopathy.

PMID- 26312950
TI  - Biotransformation of (-)-epicatechin, (+)-epicatechin, (-)-catechin, and (+)
      catechin by intestinal bacteria involved in isoflavone metabolism.
AB  - Isoflavone-metabolizing bacteria, Adlercreutzia equolifaciens, Asaccharobacter
      celatus, Slackia equolifaciens, and Slackia isoflavoniconvertens catalyzed C-ring
      cleavage of (-)-epicatechin and (+)-catechin, (+)-epicatechin, and (-)-catechin
      in varying degrees. The cleaving abilities of (-)-epicatechin and (+)-catechin
      were enhanced by hydrogen, except (+)-catechin cleavage by S. equolifaciens,
      which was not accelerated. (-)-Catechin cleavage by Ad. equolifaciens was
      remarkably accelerated by hydrogen.

PMID- 26312951
TI  - Diagnosis of asthma: the challenge goes on.

PMID- 26312952
TI  - Syntactic processing as a marker for cognitive impairment in amyotrophic lateral
      sclerosis.
AB  - Despite recent interest in cognitive changes in patients with amyotrophic lateral
      sclerosis (ALS), investigations of language function looking at the level of
      word, sentence and discourse processing are relatively scarce. Data were obtained
      from 26 patients with sporadic ALS and 26 healthy controls matched for age,
      education, gender, anxiety, depression and executive function performance.
      Standardized language tasks included confrontation naming, semantic access, and
      syntactic comprehension. Quantitative production analysis (QPA) was used to
      analyse connected speech samples of the Cookie Theft picture description task.
      Results showed that the ALS patients were impaired on standardized measures of
      grammatical comprehension and action/verb semantics. At the level of discourse,
      ALS patients were impaired on measures of syntactic complexity and fluency;
      however, the latter could be better explained by disease related factors.
      Discriminant analysis revealed that syntactic measures differentiated ALS
      patients from controls. In conclusion, patients with ALS exhibit deficits in
      receptive and expressive language on tasks of comprehension and connected speech
      production, respectively. Our findings suggest that syntactic processing deficits
      seem to be the predominant feature of language impairment in ALS and that these
      deficits can be detected by relatively simple language tests. 

PMID- 26312953
TI  - Foreword: physics of cell migration.

PMID- 26312954
TI  - The role of the local chemical environment of Ag on the resistive switching
      mechanism of conductive bridging random access memories.
AB  - Conductive bridging random access memories (CBRAMs) are one of the most promising
      emerging technologies for the next generation of non-volatile memory. However,
      the lack of understanding of the switching mechanism at the nanoscale level
      prevents successful transfer to industry. In this paper, Ag/GeSx/W CBRAM devices
      are analyzed using depth selective X-ray Absorption Spectroscopy before and after
      switching. The study of the local environment around Ag atoms in such devices
      reveals that Ag is in two very distinct environments with short Ag-S bonds due to
      Ag dissolved in the GeSx matrix, and longer Ag-Ag bonds related to an Ag metallic
      phase. These experiments allow the conclusion that the switching process involves
      the formation of metallic Ag nano-filaments initiated at the Ag electrode. All
      these experimental features are well supported by ab initio molecular dynamics
      simulations showing that Ag favorably bonds to S atoms, and permit the proposal
      of a model at the microscopic level that can explain the instability of the
      conductive state in these Ag-GeSx CBRAM devices. Finally, the principle of the
      nondestructive method described here can be extended to other types of resistive
      memory concepts. 

PMID- 26312955
TI  - Tramadol versus codeine/acetaminophen after pediatric tonsillectomy: A
      prospective, double-blinded, randomized controlled trial.
AB  - OBJECTIVE: Tonsillectomy is one of the most common pediatric surgical procedures
      performed in the United States. The postoperative period can be particularly
      painful, and there is currently no consensus on an optimal analgesic regimen. The
      objective of this study was to evaluate efficacy and safety of the single drug
      tramadol versus codeine/acetaminophen post-tonsillectomy. DESIGN: Prospective,
      double-blinded, randomized controlled trial. SETTING: Large, Midwestern US
      pediatric hospital. PATIENTS: Eighty-four children aged 4-15 years who underwent
      a tonsillectomy (with or without adenoidectomy) procedure were randomized and 74
      were included in the analysis. INTERVENTIONS: Group 1 received liquid
      codeine/acetaminophen for 10 days post-tonsillectomy (5 days scheduled, followed
      by 5 days as-needed). Group 2 received liquid tramadol for 10 days post
      tonsillectomy (5 days scheduled, followed by 5 days as-needed). MAIN OUTCOME
      MEASURES: Efficacy and side effects were evaluated using a 10-day take-home diary
      that was completed by parents. RESULTS: Children in both study arms reported
      adequate post-tonsillectomy pain management without significant differences
      between groups in pain scores. Oversedation was significantly higher on the day
      of surgery in the codeine/acetaminophen group, and itching was experienced by
      significantly more children in the tramadol group during the postoperative
      period. CONCLUSIONS: As part of multimodal analgesia, scheduled plus as-needed
      tramadol may be considered for children in the postoperative setting due to its
      analgesic properties, low potential for side effects, and good safety profile.

PMID- 26312956
TI  - Duration of intrathecal morphine effect in children with idiopathic scoliosis
      undergoing posterior spinal fusion.
AB  - OBJECTIVE: Intrathecal (IT) morphine improves pain control and decreases opioid
      requirements in children following thoracic and abdominal surgery. However,
      studies in children report variable durations of analgesia following IT morphine.
      The purpose of this study is to describe the duration of analgesia in children
      undergoing surgical correction of idiopathic scoliosis. DESIGN: Retrospective
      chart review. SETTING: Pediatric hospital within a tertiary care academic medical
      center. PARTICIPANTS: Forty-four pediatric patients with idiopathic scoliosis who
      received IT morphine following posterior spinal fusion (PSF). MAIN OUTCOME
      MEASURE(S): Mean opioid exposure 0-12 hours and 13-24 hours post-IT morphine.
      RESULTS: Mean opioid exposure was significantly increased during the 13-24-hour
      compared to the 0-12-hour time period (23.0 +/- 12.5 mg parenteral morphine vs
      15.9 +/- 1.7 mg; p = 0.0006). The only factors significantly associated with
      morphine exposure during the 0-12-hour period included the median pain score (0
      12 hours) (odds ratio [OR], 1.92; 95% confidence interval [CI], 0.033-3.80; p =
      0.046) and total acetaminophen dose (OR, 0.003; 95% CI, 0.0008-0.005; p = 0.011).
      CONCLUSIONS: These data indicate that patients experienced improved analgesia for
      at least 12 hours following IT morphine. Increased use of adjuvant analgesics
      such as acetaminophen may reduce opioid requirements following PSF procedures.
      More studies are needed to investigate the combination of adjuvants and IT
      morphine to reduce postoperative pain in this population.

PMID- 26312957
TI  - Pharmacoepidemiology of opiate use in the neonatal ICU: Increasing cumulative
      doses and iatrogenic opiate withdrawal.
AB  - OBJECTIVE: Neonatal intensive care unit (ICU) care involves use of opiates to
      treat postoperative, ventilated, or chronically ill infants. Opiates provide
      necessary analgesia and sedation, but the morbidities include prolonged neonatal
      abstinence syndrome (NAS) and extended length of stay for dose tapering. Our
      objective was to quantify trends in opiate exposure in a tertiary care NICU. The
      authors hypothesize that medical opiate exposure and resultant ICU-acquired NAS
      would increase over time. DESIGN: Retrospective cross-sectional cohort study.
      SETTING: Tertiary care NICU. PATIENTS: High-risk inborn infants admitted in
      fiscal years 2003-2004, 2007-2008, and 2010-2011. MAIN OUTCOME MEASURE: Average
      cumulative morphine exposure (all opiate doses converted to morphine equivalents)
      per time epoch was compared in cohorts of clinically similar infants. Linear
      regression was used to assess the primary outcome, assessing changes in opiate
      exposure over time. RESULTS: Sixty-three infants were included in the final
      analysis. The primary analysis assessing cumulative opiate exposure per infant
      showed an increase of 134 mg per time epoch (95% CI-12, 279 mg, p-value 0.071).
      There was a statistically significant increase in the percent of infants with a
      diagnosis of iatrogenic NAS, increasing from 9 to 35 to 50 percent (p-value
      0.012).

PMID- 26312958
TI  - Opioid prescriptions before and after high-energy trauma.
AB  - OBJECTIVE: To describe the legal use of opioids in adult patients before and
      after high-energy trauma. DESIGN: The study was a retrospective database study.
      SETTING: Clinical care outside hospitals. PATIENTS: All patients who suffered
      high-energy trauma and were brought to Odense University Hospital (OUH), Denmark,
      in 2007 and 2008 were retrieved from the trauma database. These patients were
      linked with data on opioid use from the regional prescription database. In all,
      938 patients were included. MAIN OUTCOME MEASURE: Redemption of opioid
      prescription during the 6 months prior to a multitrauma or redemption of two or
      more prescriptions for opioids 6 months or later after a multitrauma. RESULTS: Of
      the 938 patients brought to OUH with severe trauma within the study period, 61
      patients died (7 percent) and six of these had redeemed prescriptions for opioids
      within 6 months prior to the trauma (10 percent) compared to 65 patients of the
      877 survivors (7 percent) (odds ratio 1.4, nonsignificant). In all, 62 patients
      (7 percent) redeemed opioid prescriptions later than 6 months after their trauma
      and in a multivariable analysis, severe injury itself and severe injuries of the
      lower extremities were associated with redemption of opioid prescription after
      the trauma. CONCLUSIONS: The authors did not find any correlation between death
      by trauma and redemption of opioid prescriptions within the 6 months before the
      trauma. More severe traumas and especially severe traumas to the lower
      extremities were associated with redemption of opioid prescriptions after
      multitrauma.

PMID- 26312959
TI  - Triple dosing with high doses of buprenorphine: Withdrawal and plasma
      concentrations.
AB  - BACKGROUND: In maintenance treatment for opiate addiction, buprenorphine can be
      administered less frequently than daily due to its long half-life. OBJECTIVE: To
      examine the plasma concentration of buprenorphine and norbuprenorphine for 72
      hours after a dose of 72 mg and to objectively and subjectively evaluate the
      correlations between concentrations and withdrawal levels. METHODS: Patients in
      maintenance treatment with buprenorphine with a daily dose of 24 mg were given a
      triple dose of 72 mg (n = 9), in an outpatient setting. Blood samples were drawn,
      and withdrawal symptoms were evaluated objectively and subjectively every 24
      hours over 72 hours. Urine and blood toxicology samples were obtained. RESULTS:
      The triple dose was generally accepted well with low subjective and objective
      withdrawal scores. However, two patients aborted the study on day 3 and reported
      withdrawal symptoms. Benzodiazepine use was confirmed in one while the other
      likely used unauthorized buprenorphine. CONCLUSIONS: Administration of
      buprenorphine in three times the daily dose seems acceptable, also in the higher
      daily maintenance doses (here, 24 mg) used in many clinical settings. Two
      patients did not tolerate the regimen but, partly due to the outpatient setting,
      the reasons why are unclear. Further research should be of interest as high
      buprenorphine doses are becoming more common clinically.

PMID- 26312960
TI  - Impact of constipation on opioid therapy management among long-term opioid users,
      based on a patient survey.
AB  - OBJECTIVE: The authors sought to characterize health-related quality of life
      (HRQoL), medication adherence, productivity losses, and treatment satisfaction
      associated with modifications to opioid therapy due to opioid-induced
      constipation (OIC). DESIGN: A cross-sectional, between-subjects design was used
      to examine health outcomes among US noncancer participants currently taking
      opioids. PATIENTS, PARTICIPANTS: Participants were adults in the 2012 US National
      Health and Wellness Survey, who reported currently using opioids (> 30 days) and
      experiencing constipation. Respondents were categorized as making modifications
      to opioid therapy due to OIC (modifiers, n = 244) or making no modifications
      (nonmodifiers, n = 247). MAIN OUTCOME MEASURES: Patient Assessment of
      Constipation Quality of Life (PAC-QoL) and Symptoms (PAC-Sym), Morisky Medication
      Adherence Scale (MMAS-4), Work Productivity and Activity Impairment, and the
      Treatment Satisfaction Questionnaire for Medication (TSQM II) for OIC treatment
      were administered. Generalized linear models were adjusted to control for
      baseline characteristics (age, gender, comorbidities, opioid strength, etc).
      RESULTS: Modifiers reported poorer HRQoL (PAC-QoL total: 1.74 vs 1.44, p <
      0.001), worse constipation (PAC-Sym total: 1.56 vs 1.35, p = 0.003), more pain
      related resource use (surgery: odds ratio (OR) = 3.72, p = 0.002; emergency room
      visits: OR = 1.88, p = 0.049; hospitalizations: OR = 2.47, p = 0.033), and lower
      adherence (MMAS-4 pain: OR = 0.12, p < 0.001; MMAS-4 OIC: OR = 0.39, p < 0.001)
      than nonmodifiers. Modifiers reported greater presenteeism (49.75 percent vs
      38.28 percent, p = 0.038), but no significant differences were found for activity
      impairment or OIC treatment satisfaction. CONCLUSIONS: Treating OIC effectively
      may help prevent inadequate pain management secondary to opioid therapy
      modification, help increase HRQoL, lessen OIC symptoms, decrease productivity
      loss, and improve adherence to opioid and OIC treatments.

PMID- 26312961
TI  - 12-Month safety and effectiveness of once-daily hydrocodone tablets formulated
      with abuse-deterrent properties in patients with moderate to severe chronic pain.
AB  - OBJECTIVE: To characterize the long-term safety and effectiveness of HysinglaTM
      ER, single-entity, once-daily, extended-release hydrocodone bitartrate tablets
      formulated with abuse-deterrent properties (HYD), offering a new treatment option
      for appropriate patients with chronic pain. DESIGN: An open-label study with a
      dose-titration period (up to 45 days) and a maintenance period (12 months).
      PATIENTS, PARTICIPANTS: A total of 922 patients with chronic nonmalignant and non
      neuropathic moderate to severe pain received open-label HYD tablets 20-120 mg;
      728 of these achieved a stabilized dose of HYD at the end of dose-titration and
      entered the maintenance period. RESULTS: The safety profile was similar to that
      of other oral opioid analgesics, without new or unexpected safety concerns. The
      most frequent treatment-emergent adverse events (AEs; >= 5 percent) were those
      commonly associated with the use of systemic u-opioid analgesics, including
      nausea, constipation, vomiting, fatigue, dizziness, somnolence, and headache.
      There were 77 (8 percent) patients with a total of 109 nonfatal treatment
      emergent serious AEs. Few patients discontinued due to lack of therapeutic effect
      overall (6 percent), especially during the 12-month maintenance period (4
      percent). Pain relief, sleep, functional health, and activities of daily living
      all improved at the end of the dose-titration period with HYD. These improvements
      were maintained through the 12-month maintenance period with stable HYD doses and
      without increase in concomitant supplemental analgesic medications. CONCLUSIONS:
      This long-term study demonstrated the safety and long-term maintenance of
      analgesic effect of HYD without continued need for dose increase.

PMID- 26312962
TI  - Decreased responsiveness to oxycodone: A case of a pharmacokinetic drug
      interaction?
AB  - Concurrent administration of oxycodone and phenytoin may cause, through induction
      of CYP3A4 enzymes, decreased analgesic effects of oxycodone. However, no
      descriptions of this interaction exist. A patient who was on oxycodone for
      chronic back pain was admitted to the hospital. Five days after initiating
      fosphenytoin, the patient experienced a dramatic escalation in his pain and lack
      of response to oxycodone breakthrough doses. Changing oxycodone to hydromorphone
      resulted in significantly improved analgesia. Concurrent use of fosphenytoin and
      oxycodone may increase the conversion of oxycodone to inactive metabolites,
      resulting in decreased analgesia. This may be avoided using hydromorphone,
      morphine, or oxymorphone. 

PMID- 26312964
TI  - Interplay of Structure and Dynamics in Functional Macromolecular and
      Supramolecular Systems As Revealed by Magnetic Resonance Spectroscopy.

PMID- 26312963
TI  - Sleep-disordered breathing in patients with opioid use disorders in long-term
      maintenance on buprenorphine-naloxone: A case series.
AB  - BACKGROUND: Rates of opioid overdose deaths are increasing in the United States,
      leading to intensified efforts to provide medication-assisted treatments for
      opioid use disorders. It is not clear what effect opioid agonist treatments (ie,
      the u-opioid receptor full agonist methadone and the partial agonist
      buprenorphine) may have on respiratory function. However, sleep-disordered
      breathing has been documented in methadone maintenance pharmacotherapy, and there
      is emerging evidence for similar sleep-disordered breathing in buprenorphine and
      buprenorphine-naloxone maintenance treatment. OBJECTIVE: To provide further
      clinical evidence of sleep-disordered breathing emerging in the context of
      buprenorphine-naloxone maintenance pharmacotherapy. METHODS: The authors report
      two additional cases of sleep-disordered breathing that developed in patients
      with severe opioid use disorders, treated successfully as outpatients with
      buprenorphine-naloxone maintenance. Both patients provided written consent for
      their clinical information to be included in this case report, and elements of
      their identities have been masked to provide confidentiality. RESULTS: Two adult
      female patients, who were stable in buprenorphine-naloxone maintenance treatment
      developed daytime sleepiness, were referred for evaluation and found to have
      sleep-disordered breathing. One patient's daytime sleepiness improved with
      reduction in both buprenorphine-naloxone and other sedating medications as well
      as initiation of a constant positive airway pressure (CPAP) device. However, the
      other patient could not tolerate decreases in buprenorphine-naloxone and/or CPAP
      initiation and her daytime sleepiness persisted. CONCLUSION: Buprenorphine
      naloxone maintenance treatment can be associated with sleep-disordered breathing.
      It can be difficult to differentiate the cause(s) of sleep-disordered breathing
      among the effects of buprenorphine-naloxone treatment itself, co-occurring
      conditions, such as obesity and cigarette smoking or other medications, or some
      combination thereof. Regardless of etiology, sleep-disordered breathing and its
      consequences present unique challenges to the patient in recovery from an opioid
      use disorder and therefore warrants careful evaluation and management.

PMID- 26312965
TI  - Evaluation of the BlightPro Decision Support System for Management of Potato Late
      Blight Using Computer Simulation and Field Validation.
AB  - The objective of this study was to evaluate the utility of the BlightPro decision
      support system (DSS) for late blight management using computer simulation and
      field tests. Three fungicide schedules were evaluated: (i) calendar-based
      (weekly) applications, (ii) applications according to the DSS, or (iii) no
      fungicide. Simulation experiments utilized 14 years of weather data from 59
      locations in potato-producing states. In situations with unfavorable weather for
      late blight, the DSS recommended fewer fungicide applications with no loss of
      disease suppression; and, in situations of very favorable weather for late
      blight, the DSS recommended more fungicide applications but with improved disease
      suppression. Field evaluation was conducted in 2010, 2011, 2012, and 2013. All
      experiments involved at least two cultivars with different levels of resistance.
      DSS-guided and weekly scheduled fungicide treatments were successful at
      protecting against late blight in all field experiments. As expected, DSS-guided
      schedules were influenced by prevailing weather (observed and forecast) and host
      resistance and resulted in schedules that maintained or improved disease
      suppression and average fungicide use efficiency relative to calendar-based
      applications. The DSS provides an interactive system that helps users maximize
      the efficiency of their crop protection strategy by enabling well-informed
      decisions. 

PMID- 26312966
TI  - 'Candidatus Liberibacter solanacearum' Titers in and Infection Effects on Potato
      Tuber Chemistry of Promising Germplasm Exhibiting Tolerance to Zebra Chip
      Disease.
AB  - Long-term sustainable management of zebra chip (ZC) disease of potato requires
      development of tolerant or resistant germplasm. To this end, 283 potato varieties
      and breeding clones were infected with the ZC putative causal agent 'Candidatus
      Liberibacter solanacearum' (Lso) by potato psyllid vector inoculations in 2010,
      2011, 2012, and 2013. Potato germplasm was then examined for development of fresh
      and fried ZC symptoms. Over multiple years 29 breeding clones exhibited little to
      no symptoms in freshly cut tuber slices, and five exhibited little to no symptoms
      in fried slices. These five presumed tolerant breeding clones were chosen for
      further screening to determine whether the lack of physiological responses to Lso
      infection was the cause of observed tolerance. To this end, tuber amino acid,
      sugar, and phenolic levels were compared between noninfected and Lso-infected
      plants. The five putative tolerant clones had less dramatic shifts in host
      physiology following Lso infection than the susceptible Atlantic cultivar. This
      suggested lack of host responses to Lso infection that result in major changes in
      tuber biochemistry is a potential mechanism of ZC resistance. However, the
      susceptible Atlantic cultivar did have consistently greater Lso titers compared
      with two of the tolerant entries, so for these reductions in Lso pathogen
      progression also might be a factor. Regardless, lack of host responses could
      still remain one trait that could be used to aid in selection of ZC-resistant
      potato varieties, as other tolerant lines had infection levels consistent with
      susceptible Atlantic cultivar. These results also suggest that germplasm derived
      from relatives of cultivated potato plants are viable sources of ZC disease
      resistance. 

PMID- 26312967
TI  - Long-term Short Implants Performance: Systematic Review and Meta-Analysis of the
      Essential Assessment Parameters.
AB  - Lack of standard criteria in the outcome assessment makes it difficult to draw
      conclusions on the clinical performance of short implants and, under these
      circumstances, determine the reasons for implant failure. This study evaluated,
      through a systematic review of the literature and meta-analysis, the essential
      parameters required to assess the long-term clinical performance of short and
      extra-short implants. Electronic databases (Pubmed-MEDLINE, Cochrane Library
      Database, Embase, and Lilacs) were searched by two independent reviewers, without
      language limitation, to identify eligible papers. References from the selected
      articles were also reviewed. The review included clinical trials involving short
      dental implants placed in humans, published between January 2000 and March 2014,
      which described the parameters applied for outcome's measurements and provided
      data on survival rates. Thirteen methodologically acceptable studies were
      selected and 24 parameters were identified. The most frequent parameters assessed
      were the marginal bone loss and the cumulative implant survival rate, followed by
      implant failure rate and biological complications such as bleeding on probing and
      probing pocket depths. Only cumulative implant survival rate data allows meta
      analysis revealing a positive effect size (from 0.052 (fixed) to 0.042 (random)),
      which means that short implant appears to be a successful treatment option.
      Mechanical complications and crown-to-implant (C/I) ratio measurement were also
      commonly described, however, considering the available evidence; no strong
      conclusions could be drawn since different methods were used to assess each
      parameter. By means of this literature review, a standard evaluation scheme is
      proposed, being helpful to regiment further investigations and comparisons on
      future studies. 

PMID- 26312968
TI  - Experimental Furcal Perforation Treated with MTA: Analysis of the Cytokine
      Expression.
AB  - The aim of this study was to evaluate mineral trioxide aggregate (MTA)-induced
      cytokine expression in mice after experimental furcal perforation. BALB/c mice
      (n=5) were subjected to induced furcal drilling of the maxillary first molar
      followed by MTA sealing in the left side (experimental group) and paraffin
      sealing in the right side (control group). Animals were euthanized at 7, 14 and
      21 days after sealing the perforations. The expression levels of the IFN-gamma,
      TNF-alpha, IL-10, IL-4, TGF-beta and RANKL genes were investigated by real time
      polymerase chain reaction (PCR) in the teeth and surrounding tissues. In the
      experimental groups, after the 7th day, there was a down-regulation of the mRNA
      levels of TNF-alpha and IL-4 compared to the 14th day (p<0.05). In these groups,
      the mRNA levels of RANKL, IFN-gamma and TNF-alpha were statistically higher after
      14 days compared to 21 days post-MTA sealing (p<0.05). The level of IL-10 mRNA
      was increased at the 21st day (p<0.05). The mRNA expression of TGF-beta did not
      exhibit any statistically relevant results. There was a statistical down
      regulation of IL-4 gene expressions when control and experimental groups were
      compared at days 7 and 21. In conclusion, MTA sealing favored the expression of
      pro-inflammatory cytokines in the intermediate phase of the immuno-inflammatory
      response (14th day). The reduction of these cytokines in later phase of the
      response was probably due to immunoregulation by IL-10. 

PMID- 26312969
TI  - Effect of Passive Ultrasonic Irrigation on Enterococcus faecalis from Root
      Canals: An Ex Vivo Study.
AB  - Endodontic irrigation aims to clean and disinfect the root canal system. Passive
      ultrasonic irrigation (PUI) is based on the use of an ultrasound-activated
      instrument into the root canal filled with irrigant. The aim of this study was to
      evaluate, ex vivo, the effectiveness of PUI in eliminating Enterococcus faecalis
      from root canals. Seventy-five extracted human single-root teeth were used. After
      root canal preparation, specimens were inoculated with E. faecalis and incubated
      at 37  degrees C for 21 days. Specimens were distributed into five groups (n=15),
      according to the irrigation method: PUI + saline solution (PUI/SS); PUI + 1%
      NaOCl (PUI/NaOCl); conventional needle irrigation (CNI) + saline solution
      (CNI/SS); CNI + 1% NaOCl (CNI/NaOCl); No irrigation (control). Microbiological
      samples were collected at three time points: initial (21 days after inoculation),
      post-irrigation (immediately after irrigation), and final (7 days after
      irrigation). Data were obtained in CFU mL-1 and subjected to analysis by ANOVA
      and Tukey's tests at 5% significance level. The post-irrigation samples did not
      demonstrate statistical difference between PUI/SS and CNI/SS nor between
      PUI/NaOCl and CNI/NaOCl (p>0.05), but PUI/NaOCl and CNI/NaOCl had lower CFU mL-1
      number than the other groups (p>0.05). Statistically significant difference was
      observed between the initial and post-irrigation samples and between the post
      irrigation and final samples (p<0.05) in all groups, except in the control. The
      final samples of all groups presented bacterial counts similar to the initial
      samples. PUI or CNI with 1% NaOCl contribute to disinfection, but are unable to
      eradicate E. faecalis from the root canal system. 

PMID- 26312970
TI  - Effects of Different Rotary Files Combined with Different Irrigation Needles on
      Apically Extruded Debris.
AB  - The aim of this study was to compare the apically extruded debris associated with
      ProTaper Next and OneShape Apical files using two different irrigation needles,
      open-ended and closed-ended (Max-I-Probe). Forty-eight mandibular premolars were
      assigned to four groups (n=12) as follows: Group PTN-SN: Root canal was prepared
      with ProTaper Next (PTN) and irrigated with open-ended standard needle; Group PTN
      MP: Root canal was prepared with PTN and irrigated with Max-I-Probe; Group OSA
      SN: Root canal was prepared with OneShape Apical (OSA) and irrigated with open
      ended needle; Group OSA-MP: Root canal was prepared with OSA and irrigated with
      Max-I-Probe. Debris extruded during instrumentation was collected into pre
      weighed Eppendorf tubes. After storage in an incubator at 70  degrees C for 5
      days, the Eppendorf tubes were weighed to obtain the final weight with extruded
      debris. The difference between pre-and post-debris weights was calculated and
      statistical analysis was performed using Kruskal-Wallis and Mann-Whitney U tests
      (p<0.05). No statistically significant difference was observed between files and
      needles regarding amount of apically extruded debris (p>0.05). OneShape Apical
      and ProTaper Next resulted in extrusion of debris beyond the apical foramen,
      regardless of needle tip. 

PMID- 26312971
TI  - Identification of Apical and Cervical Curvature Radius of Human Molars.
AB  - To determine the frequency of apical and cervical curvatures in human molars
      using the radius method and cone-beam computed tomography (CBCT) images. Four
      hundred images of mandibular and maxillary first and second molars were selected
      from a database of CBCT exams. The radius of curvature of curved root canals was
      measured using a circumcenter based on three mathematical points. Radii were
      classified according to the following scores: 0 - straight line; 1 - large radius
      (r > 8 mm, mild curvature); 2 - intermediate radius (r > 4 and r < 8 mm, moderate
      curvature); and 3 - small radius (r <= 4 mm, severe curvature). The frequency of
      curved root canals was analyzed according to root canal, root thirds, and coronal
      and sagittal planes, and assessed using the chi-square test (significance at
      alpha = 0.05). Of the 1,200 evaluated root canals, 92.75% presented curved root
      canals in the apical third and 73.25% in the cervical third on coronal plane
      images; sagittal plane analysis yielded 89.75% of curved canals in the apical
      third and 77% in the cervical third. Root canals with a large radius were
      significantly more frequent when compared with the other categories, regardless
      of root third or plane. Most root canals of maxillary and mandibular first and
      second molars showed some degree of curvature in the apical and cervical thirds,
      regardless of the analyzed plane (coronal or sagittal).

PMID- 26312972
TI  - Glycerol Salicylate-based Pulp-Capping Material Containing Portland Cement.
AB  - The purpose of this study was to evaluate the water sorption, solubility, pH and
      ability to diffuse into dentin of a glycerol salicylate-based, pulp-capping
      cement in comparison to a conventional calcium hydroxide-based pulp capping
      material (Hydcal). An experimental cement was developed containing 60% glycerol
      salicylate resin, 10% methyl salicylate, 25% calcium hydroxide and 5% Portland
      cement. Water sorption and solubility were determined based on mass changes in
      the samples before and after the immersion in distilled water for 7 days.
      Material discs were stored in distilled water for 24 h, 7 days and 28 days, and a
      digital pHmeter was used to measure the pH of water. The cement's ability to
      diffuse into bovine dentin was assessed by Raman spectroscopy. The glycerol
      salicylate-based cement presented higher water sorption and lower solubility than
      Hydcal. The pH of water used to store the samples increased for both cements,
      reaching 12.59 +/- 0.06 and 12.54 +/- 0.05 after 7 days, for Hydcal and glycerol
      salicylate-based cements, respectively. Both cements were able to turn alkaline
      the medium at 24 h and sustain its alkalinity after 28 days. Hydcal exhibited an
      intense diffusion into dentin up to 40 um deep, and the glycerol salicylate-based
      cement penetrated 20 um. The experimental glycerol salicylate-based cement
      presents good sorption, solubility, ability to alkalize the surrounding tissues
      and diffusion into dentin to be used as pulp capping material.

PMID- 26312973
TI  - Indirect Restoration Thickness and Time after Light-Activation Effects on Degree
      of Conversion of Resin Cement.
AB  - This study evaluated the effects of indirect restorative materials, curing
      conditions and time on the degree of conversion (DC) of a dual-cured resin cement
      using infrared spectroscopy. The resin cement (RelyX Unicem 2, 3M ESPE) was
      applied to the diamond surface of a horizontal attenuated-total-reflectance unit
      and activated using one of following conditions: self-cure, direct light
      exposure, light exposure through indirect restorative materials (resin nano
      ceramic: Lava Ultimate, 3M ESPE or feldspathic ceramic: Vita Blocks Mark II, Vita
      Zahnfabrik). Four thicknesses (0.5, 1.0, 1.5 or 2.0 mm) of each indirect material
      were analyzed, and the light-activation was performed using a blue LED light.
      Data (n=5) were analyzed by three-way ANOVA, Tukey's post hoc and Dunnett's tests
      (alpha=5%). No significant differences in DC were observed between indirect
      materials of similar thickness. All groups exhibited higher DC after 10 min than
      after 5 min. At both times points, the self-cure group exhibited significantly
      lower DC than all the light exposure groups. Only when the overlying indirect
      restoration had a thickness of 2 mm did DC decrease significantly. The presence
      of a thick, indirect restoration can decrease the DC of resin cement. DC after 10
      min was higher than after 5 min. The self-cure mode yielded lower DC than the
      light-activating one. 

PMID- 26312974
TI  - Effect of Fluoride and Simplified Adhesive Systems on the Bond Strength of
      Primary Molars and Incisors.
AB  - The aim of this study was evaluate in vitro the influence of simplified adhesive
      systems (etch-and-rinse and self-etching) and 1.23% acidulated phosphate fluoride
      (APF) on the microshear bond strength (MU-SBS) of composite resins on primary
      molars and incisors. Forty primary molars and forty incisors vestibular enamel
      was treated with either the self-etching Clearfil SE Bond (CSE, Kuraray) or etch
      and-rinse Adper Single Bond 2 (SB2, 3M/ESPE) adhesive system. Each group was
      subdivided based on the prior treatment of the enamel with or without the topical
      application of 1.23% APF. Thereafter, matrices were positioned and filled with
      composite resin and light cured. After storage in distilled water at 37 +/- 1
      degrees C for 24 h, the specimens were submitted to MU-SBS in a universal testing
      machine. Kruskal-Wallis and Mann-Whitney tests (p < 0.05) showed that the prior
      application of 1.23% APF led to a significant reduction in bond strength. The
      type of adhesive exerted no significant influence bond strength. In the inter
      group analysis, however, significantly bond strength reduction was found for the
      incisors when CSE was employed with APF. Adhesive failure was the most common
      type of fracture. The bond strength was affected by the prior application of
      1.23% APF and type of tooth.

PMID- 26312975
TI  - In Vitro Evaluation of the Efficacy of Different Over-the-Counter Products on
      Tooth Whitening.
AB  - This in vitro study evaluated the whitening effect of four different over-the
      counter products compared with a 10% carbamide peroxide (CP) bleaching gel.
      Specimens obtained from bovine incisors were stained in a tea solution and
      randomly divided into six groups according to the product used (n=10): CT:
      conventional toothpaste (negative control); CWT: Crest 3D White toothpaste; CWR:
      Crest 3D White mouth rinse; CWS: Crest 3D White strips; DW: Dazzling White (paint
      on gel); and OP: Opalescence PF 10% CP (at-home bleaching gel, positive control).
      Over-the-counter products and 10% CP were used according to the manufacturer's
      recommendations. Color measurements were performed according to the CIELab system
      using spectrophotometer after staining, and after 4 and 8 weeks of the treatment
      procedure. The ?E, ?L, ?a, and ?b values were calculated. The data obtained were
      analyzed by repeated-measures ANOVA. Tukey's test for multiple comparisons was
      applied (p<0.05). All groups, except CWT, were effective in tooth whitening in
      comparison with conventional toothpaste. There was no significant difference in
      tooth whitening between CWT and CT (p=0.93). CWS, DW and OP groups presented
      significantly higher color changes than the CWR group. DW and CWS showed similar
      tooth whitening to OP. 

PMID- 26312976
TI  - At-Home Bleaching: Color Alteration, Hydrogen Peroxide Diffusion and
      Cytotoxicity.
AB  - This study evaluated the color change, cytotoxicity and hydrogen peroxide (HP)
      diffusion caused by different home bleaching protocols: 10% carbamide peroxide
      (CP) for 3 or 1.5 h, 6% hydrogen peroxide for 1.5 h or 45 min. To quantify the
      peroxide penetration, disks of bovine teeth were placed in artificial pulp
      chambers (APCs) containing acetate buffer, which was collected for evaluation in
      a spectrophotometer. For analysis of cytotoxicity, specimens were adapted in APCs
      containing culture medium, which subsequently was applied on MDPC-23 odontoblast
      like cells for 1 h. Cellular metabolism was evaluated by methyl tetrazolium (MTT)
      assay and the color change of the specimens was analyzed using the CIE L * a * b
      * system. The data were submitted to ANOVA and Fisher test (alpha=5%). The
      treatment with 10% CP for 3 h was the most effective, and 6% HP for 45 min
      produced the lowest color change. The groups 10% CP for 1.5 h and 6% HP for 45
      min had the lowest trans-enamel dentinal HP penetration, and the 6% HP for 1.5 h
      had the highest. None of the protocols affected cellular metabolism and
      morphology. In conclusion, reduced peroxide exposure time reduced the bleaching
      result; higher HP diffusion did not mean higher effectiveness. 

PMID- 26312977
TI  - Enamel Quality after Debonding: Evaluation by Optical Coherence Tomography.
AB  - The aims of this study were to evaluate quantitatively the enamel fractures,
      adhesive remnants and bracket fragments on enamel after debonding of metal and
      ceramic brackets, and to quantify the layer of adhesive remnants in depth after
      two different cleanup procedures. Metal and ceramic brackets were bonded on 120
      human incisors and then debonded using two different techniques with Side Cutter
      (SC) and Anterior Bracket Removal plier (ABR). After this, a high-speed tungsten
      carbide finishing bur or a low-speed tungsten carbide finishing bur was used. The
      debonded samples were submitted to enamel assessment with optical coherence
      tomography (OCT). In sequence, two different methods of removing the remaining
      adhesive (tungsten carbide burs at high and low speed) were performed and at the
      end of these procedures, the remaining adhesive layer was measured with OCT. The
      results demonstrated that enamel fractures were observed only in the samples
      bonded with ceramic brackets, and the type of pliers did not influence the
      incidence and extent of enamel damage. Moreover, the type of debonding technique
      (with side-cutting pliers or anterior bracket removal pliers) and the type of
      bracket did not influence the amount of adhesive remaining after debonding. The
      burs at low speed removed the remaining adhesive more effectively during cleanup
      procedures. 

PMID- 26312978
TI  - Influence of Resin Cements on the Tension Force of Cast Frameworks Made by the
      Technique of Framework Cemented on Prepared Abutments.
AB  - This study evaluated the tension force of cast frameworks made by the technique
      of framework cemented on prepared abutments using two different resin cements.
      Forty multi-unit abutment analogs were individually fixed with chemically cured
      acrylic resin inside PVC cylinders using a parallelometer. Brass cylindrical
      abutments were tightened to the multi-unit abutments to be used as spacers and
      then castable UCLA abutments were positioned above. These abutments were cast
      with Ni-Cr and then divided into 4 groups (n=10): cemented with RelyX U100(r);
      cemented with RelyX U100(r) and simulation of acrylic resin polymerization
      process; cemented with Multilink(r); and cemented with Multilink(r) and
      simulation of acrylic resin polymerization process. Abutments were cemented
      according to manufacturers' instructions. In a universal testing machine, tensile
      strength was applied in the direction of the long axis of the abutments at 1
      mm/min crosshead speed until displacement of the luted abutments was obtained.
      The values of maximum tensile force (N) required for the displacement of the
      luted abutments were tabulated and analyzed statistically by one-way ANOVA with a
      95% confidence level. No statistically significant difference was found among the
      groups (p>0.05). There was an increase in mean tension force when the specimens
      were subjected to the simulation of acrylic resin polymerization process, but the
      results did not differ statistically. Both resin cements presented positive
      results as regards the retention of luted abutments on their respective multi
      unit abutments. Both materials may be indicated for the technique of framework
      cemented on prepared abutments when professionals pursuit better adaptation of
      implant-supported frameworks. 

PMID- 26312979
TI  - A Modified Photoactivation Protocol Using Two Simultaneous Light-Curing Units for
      Bonding Brackets to Enamel.
AB  - This study investigated the effect of a modified photoactivation protocol using
      two simultaneous light-curing units on the shear bond strength (SBS) of brackets
      to enamel. Metal brackets were bonded to bovine incisors using the resin-based
      orthodontic cement Transbond XT (3M Unitek). Four photoactivation protocols of
      the orthodontic cement were tested (n = 15): CONTROL: photoactivation for 10 s on
      each proximal face of the bracket at a time; Simultaneous: photoactivation for 10
      s on both proximal faces of the bracket at the same time; One side-20s:
      photoactivation for 20 s at one proximal face of the bracket only; and One side
      10s: photoactivation for 10 s only at one proximal face of the bracket. SBS was
      tested immediately or after 1000 thermal cycles. Adhesive remnant index (ARI) was
      classified. Data were subjected to two-way ANOVA and Student-Newman-Keuls' test
      (alpha = 0.05). Pooled means +/- standard deviations for SBS to enamel (MPa)
      were: 10.2 +/- 4.2 (CONTROL), 9.7 +/- 4.5 (Simultaneous), 5.6 +/- 3.1 (One side
      20s), and 4.6 +/- 1.9 (One side-10s). Pooled SBS data for immediate and thermal
      cycled groups were 6.3 +/- 2.6 and 8.8 +/- 5.2. A predominance of ARI scores 1-2
      and 0-1 was observed for the immediate and thermally cycled groups, respectively.
      In conclusion, simultaneous photoactivation of the orthodontic cement using two
      light-curing units, one positioned at each proximal face of the bracket, yielded
      similar bonding ability compared to the conventional light-curing method.
      Photoactivation of the orthodontic cement at one proximal face of the bracket
      only is not recommended, irrespective of the light-curing time used.

PMID- 26312980
TI  - External Hexagon Deformation in Implants Subjected to Internal Torque.
AB  - Failures may occur in the connections of dental implants, especially in external
      hexagon (EH). Due to the deformations in this portion of implants, this study
      aimed to evaluate the levels of deformation of EH connections subjected to
      internal toque. Two types of implants were used: N group and S group. Torques of
      0, 32, 45, 60 and 80 Ncm were applied to the N group, and torques of 0, 30, 40,
      60 and infinite Ncm were applied to the S group implants. The internal distance
      (ID), internal area (IA) and external area (EA) of the EH were obtained from
      digital pictures, which were analyzed by a specific software. Statistical
      analysis was performed by the Scott-Knott test. The results showed that the
      higher the torque applied, the greater were the changes in the evaluated
      dimensions in both groups. In the S group, torque levels equal or greater than 40
      Ncm and 30 Ncm caused greater deformation of EA and IA respectively, while in the
      N group, torque levels equal or greater than 60 Ncm and 32 Ncm caused greater
      deformation of EA and IA respectively. Levels of deformation were greater in the
      S group as compared with the N group. These findings suggest that the IA, EA and
      ID of the EH may be affected by different internal torque levels. 

PMID- 26312981
TI  - Effects of Denture Cleansers on Heat-Polymerized Acrylic Resin: A Five-Year
      Simulated Period of Use.
AB  - This study evaluated color stability, surface roughness and flexural strength of
      acrylic resin after immersion in alkaline peroxide and alkaline hypochlorite
      solutions, simulating a five-year-period of use. Sixty disc-shaped (16 x 4 mm)
      and 60 rectangular specimens (65 x 10 x 3.3 mm) were prepared from heat
      polymerized acrylic resin (Lucitone 550) and assigned to 3 groups (n = 20) of
      immersion (20 min): C1: distilled water; AP: warm water and one alkaline peroxide
      tablet; SH: 0.5% NaOCl solution. Color data (?E) were determined by a colorimeter
      and also quantified according to the National Bureau of Standards units. A
      rugosimeter was used to measure roughness (MUm) and the flexural strength (MPa)
      was measured using a universal testing machine. Data were evaluated by Kruskal
      Wallis followed by Dunn tests (color stability and surface roughness) and by one
      way ANOVA and Bonferroni test (flexural strength). For all tests was considered
      alpha = 0.05. AP {0.79 (0.66;1.42)} caused color alteration significantly higher
      than C1 {0.45 (0.37;0.57)} and SH {0.34 (0.25;0.42)}. The mean ?Epsilon values
      quantified by NBS were classified as "trace" for C1 (0.43) and SH (0.31) and
      "slight" for AP (0.96). SH {-0.015 (-0.023;0.003)} caused significantly higher
      DeltaRa than the C1 {0.000 (-0.004;0.010)} and AP {0.000 (-0.009;0.008)} groups.
      There was no statistically significant difference among the solutions for
      flexural strength (C1: 84.62 +/- 16.00, AP: 85.63 +/- 12.99, SH: 84.22 +/-
      14.72). It was concluded that immersion in alkaline peroxide and NaOCl solutions
      simulating a five-year of 20 min daily soaking did not cause clinically
      significant adverse effects on the heat-polymerized acrylic resin.

PMID- 26312982
TI  - Dose-responses of Stem Cells from Human Exfoliated Teeth to Infrared LED
      Irradiation.
AB  - Despite several reports regarding tissue regeneration, including pulp repair
      induced by different light sources, only limited data have been reported
      concerning the effects of light-emitting diodes (LED) on stem cells from human
      exfoliated deciduous teeth (SHEDs). The aim of this study was to evaluate the
      effects of different energy densities of infrared LED on the cell viability,
      number of cells and mineralized tissue production by SHEDs. SHEDs were obtained
      from near-exfoliation primary teeth (n=3), seeded in plain DMEM (104 cells/cm2),
      and irradiated by a LED prototype (LEDTable 850 nm, 40 mW/cm2) delivering 0
      (control), 2, 4, 8, 15 or 30 J/cm2 (n=9). Cell viability (MTT assay), cell
      proliferation (trypan blue assay), and mineralized nodule (MN) formation
      (alizarin red stain) were assessed 12 and 72 h post-irradiation. Data were
      subjected to Kruskal-Wallis and Mann-Whitney tests (alpha=0.05). Cells irradiated
      with 2 or 4 J/cm2 exhibited higher metabolism at 72 h, and all energy densities
      provided increase in cell proliferation after 12 h. Regarding MN formation, the
      best results were observed at 72 h after SHED irradiation with 8 and 15 J/cm2. It
      was concluded that the cell viability, cell number and MN formation by pulp cells
      are enhanced after exposure to infrared LED irradiation. Overall, the greatest
      SHED biostimulation was obtained with 4 and 8 J/cm2. 

PMID- 26312983
TI  - Cellular Proliferation Index between Carcinoma Ex-Pleomorphic Adenoma and
      Pleomorphic Adenoma.
AB  - Carcinoma ex pleomorphic adenoma (CXPA) has been considered an interesting model
      of carcinogenesis, presenting various histological subtypes and invasiveness
      phase. The objective was to determine the proliferative index of CXPA and
      comparing to pleomorphic adenoma (PA). Thirty six cases of CXPA (36 PA) and 22
      areas of PA in CXPA (residual PA) were studied by Ki-67 expression. All CXPA
      cases were classified according to invasiveness phase (intracapsular, minimally
      and frankly invasive) and histopathological subtypes. Data was statistically
      analyzed by Wilcoxon, Mann-Whitney and Kruskal-Wallis tests. CXPA included 5
      intracapsular, 9 minimally invasive and 22 frankly invasive cases. Fifteen cases
      corresponded to salivary duct carcinoma, 7 to adenocarcinoma NOS, 7
      myoepithelial, 5 epithelial-myoepithelial, one case of squamous cell and one case
      of sarcomatoid carcinoma. The Ki-67 index of PA and residual PA were
      significantly lower than CXPA. Intracapsular and minimally invasive showed
      smaller proliferative index than frankly invasive. Considering the subtypes of
      CXPA, there was not a statistic difference among them. Ki-67 is a useful marker
      in the differential diagnosis of PA and CXPA, even when in the early invasive
      phase. 

PMID- 26312984
TI  - Use of Fusidic Acid for Desquamative Gingivitis Treatment: 1-Year Follow-Up.
AB  - This study evaluated retrospectively the effect of fusidic acid on the management
      of desquamative gingivitis (DG). The study population consisted of 15 patients
      with DG. Patients were requested to make topical application of 2% fusidic acid
      ointment 4 times a day for 6 weeks. Clinical assessments were recorded at
      baseline, at 6 weeks and 12 months after beginning the therapy. Patients'
      examination involved lesion size area, pain score and impact on daily activities.
      All patients presented lesions in maxilla; in 9 patients (60.0%) lesions were
      predominately at the anterior region and 6 (40.0%) at the posterior region of
      maxilla. Treatment significantly (p < 0.05) reduced the pain intensity (from 5.4
      +/- 1.12 to 1.16 +/- 0.97) and its periodicity (from 53.33% with pain > 3 x/week
      to 13.33%), and the lesion size in 72.47% (+/- 4.12) immediately after 6 weeks of
      treatment. Improvements were sustained for 12 months compared to baseline (p <
      0.001). It also reduced the impact of disease in daily activities (eating and
      oral hygiene performance), and improved the emotional condition of patients, who
      reported better social relationships and habits. Topical application of fusidic
      acid may be a possible alternative local palliative therapy for desquamative
      gingivitis treatment.

PMID- 26312985
TI  - Parental Perceptions of Oral Health Status in Preschool Children and Associated
      Factors.
AB  - The aim of the present study was to evaluate parental perceptions of oral health
      status in preschool children. A cross-sectional study was carried with 843
      Brazilian children between 3 and 5 years of age. Parents/guardians answered a
      self-administered questionnaire on the health of their children and
      sociodemographic data. Parental perceptions of their child's oral health were
      determined by the responses to the following question: "How would you describe
      your child's oral health?" The Brazilian version of the Early Childhood Oral
      Health Impact Scale (B-ECOHIS) was answered by parents/guardians and used to
      measure the impact of oral health-related quality of life (OHRQoL) on preschool
      children and their families. Three examiners performed oral exams on the children
      (K= 0.85-0.90). Descriptive analytical statistics were carried out, followed by
      logistic regression for complex samples (alpha=5%). The following variables were
      significantly associated with parental perceptions of children's oral health:
      parental perception of general health as poor (OR=18.25; 95% CI: 3.36-98.96),
      negative impact on family's OHRQoL (OR=13.82; 95% CI: 4.27-44.72), child aged
      five years (OR=7.40; 95% CI: 1.49-36.63) and the interaction between history of
      toothache and dental caries (OR=10.02; 95% CI: 1.17-85.61). Thus, parental
      perceptions of oral health are influenced only by clinical conditions with
      symptoms, such as dental caries with toothache. Other oral conditions, such as
      malocclusion or traumatic dental injury, were not associated with parental
      perceptions of their child's oral health. 

PMID- 26312986
TI  - cGVHD-Related Caries and Its Shared Features with Other 'Dry-Mouth'-Related
      Caries.
AB  - Several systemic diseases and their medical treatment may predispose the
      development of aggressive dental caries. Head and neck radiotherapy,
      chemotherapy, Sjogren's syndrome and long-standing treatment with drugs that
      induce hyposalivation are some of these conditions. The aim of this article is to
      describe the clinical features of five patients who developed chronic graft
      versus-host-disease (cGVHD) as a complication of allogeneic hematopoietic stem
      cell transplantation (allo-HSCT) and, in spite of close dental follow-up,
      subsequently developed rampant caries. In these cases, the restorations showed
      early failure and the caries still progressed until generalized teeth
      destruction. The majority of the teeth therefore had to be extracted due to
      advanced dental caries and rapid clinical progression. Herein the term "cGVHD
      related caries" is proposed to describe this under-recognized complication of
      cancer treatment that may evolve in allo-HSCT recipients that develop cGVHD. This
      condition is poorly recognized in the literature and may represent the final
      result of the clustering of oral complications in cGVHD patients, including
      mucositis, oral pain, hyposalivation, taste loss and oral infections, leading to
      rampant caries due to impaired oral hygiene and increased intake of highly
      cariogenic food. Consequently, the knowledge of this oral complication should
      improve the medical and dental management of cGVHD oral manifestations and
      improve the quality of life of patients with this post allo-HSCT complication. 

PMID- 26312987
TI  - Marine Isolates of Trimastix marina Form a Plesiomorphic Deep-branching Lineage
      within Preaxostyla, Separate from Other Known Trimastigids (Paratrimastix n.
      gen.).
AB  - Trimastigids are free-living, anaerobic protists that are closely related to the
      symbiotic oxymonads, forming together the taxon Preaxostyla (Excavata:
      Metamonada). We isolated fourteen new strains morphologically corresponding to
      two species assigned to Trimastix (until now the only genus of trimastigids),
      Trimastix marina and Trimastix pyriformis. Unexpectedly, marine strains of
      Trimastix marina branch separately from freshwater strains of this morphospecies
      in SSU rRNA gene trees, and instead form the sister group of all other
      Preaxostyla. This position is confirmed by three-gene phylogenies.
      Ultrastructural examination of a marine isolate of Trimastix marina demonstrates
      a combination of trimastigid-like features (e.g. preaxostyle-like I fibre) and
      ancestral characters (e.g. absence of thickened flagellar vane margins),
      consistent with inclusion of marine T. marina within Preaxostyla, but also
      supporting its distinctiveness from 'freshwater T. marina' and its deep-branching
      position within Preaxostyla. Since these results indicate paraphyly of Trimastix
      as currently understood, we transfer the other better-studied trimastigids to
      Paratrimastix n. gen. and Paratrimastigidae n. fam. The freshwater form
      previously identified as T. marina is described as Paratrimastix eleionoma n.
      sp., and Trimastix pyriformis becomes Paratrimastix pyriformis n. comb. Because
      of its phylogenetic position, 'true' Trimastix is potentially important for
      understanding the evolution of mitochondrion-related organelles in metamonads. 

PMID- 26312989
TI  - CeA-NPO circuits and REM sleep dysfunction in drug-refractory epilepsy.

PMID- 26312988
TI  - Epilepsy care in the southern Caribbean.
AB  - Very little has been reported about the health resources available for patients
      with epilepsy in the five English-speaking southern Caribbean countries of
      Trinidad and Tobago, Barbados, Grenada, Saint Vincent and the Grenadines, and
      Saint Lucia. There is no comprehensive resource describing their health systems,
      access to specialty care, antiepileptic drug (AED) use, and availability of brain
      imaging and EEG. The purpose of this study was to profile epilepsy care in these
      countries as an initial step toward improving the standard of care and
      identifying gaps in care to guide future policy changes. In each southern
      Caribbean country, we conducted study visits and interviewed health-care
      providers, government health ministers, pharmacy directors, hospital medical
      directors, pharmacists, clinic staff, radiologists, and radiology and EEG
      technicians. Health-care providers completed extensive epilepsy care surveys. The
      five countries all have integrated government health systems with clinics and
      hospitals that provide free or heavily subsidized care and AEDs for patients with
      epilepsy. Only Trinidad and Tobago and Barbados, however, have neurology
      specialists. The three smaller countries lack government imaging and EEG
      facilities. Trinidad had up to one-year waits for public MRI/EEG. Government
      formularies in Grenada, Saint Vincent and the Grenadines, and Saint Lucia are
      limited to first-generation AEDs. One or more second-line agents are formulary in
      Trinidad and Barbados. Nonformulary drugs may be obtained for individual patients
      in Barbados. Grenada, Saint Lucia, and Saint Vincent and the Grenadines
      participate in an Organization of Eastern Caribbean States formulary purchasing
      system, which added levetiracetam following the survey. Newer generic AED
      formulations with the lowest risks for pregnancy malformation were not in use. In
      conclusion, patients with epilepsy in the southern Caribbean have excellent
      access to government clinics and hospitals, but AED choices are limited. Local
      medical providers reported that the major limitations in care were lack of
      specialty care, lack of imaging and EEG services, financial barriers to care,
      long wait times for care, and limited access to additional AEDs. 

PMID- 26312990
TI  - STN-PPTg circuits and REM sleep dysfunction in drug-refractory epilepsy.

PMID- 26312991
TI  - Vibronic Spectrum of the Jet-Cooled 2,6-Dimethylbenzyl Radical in a Corona
      Excitation.
AB  - A jet-cooled 2,6-dimethylbenzyl radical was generated for the first time from a
      precursor 2,6-dimethylbenzyl chloride with a large amount of inert carrier gas He
      in a corona-excited supersonic expansion using a pinhole type glass nozzle. The
      visible fluorescence emanating from the jet was recorded with a long path
      monochromator to observe the vibronically resolved jet-cooled emission spectrum.
      The spectrum was analyzed to obtain accurate electronic transition and active
      vibrational mode frequencies in the ground electronic state by comparison with
      those from an ab initio calculation. 

PMID- 26312992
TI  - Cryogenic Charge Transport in Oxidized Purple Bacterial Light-Harvesting 1
      Complexes.
AB  - We report on the analysis of the inter-bacteriochlorophyll a (BChla) charge
      transport process that occurs in oxidized purple bacterial light-harvesting 1
      (LH1) complexes. Experimentally, charge migration within oxidized LH1 is
      monitored by following the temperature-dependent changes of the BChla(*)(+)
      electron paramagnetic resonance (EPR) line-shape characteristics. At 6 K, a
      Gaussian-shaped spectrum with a 1.3-mT width is detected. These characteristics
      indicate that at extremely low temperatures charge transport is substantially
      slowed so that the unpaired electron is localized on one or two BChlas. At higher
      temperatures, the spectra exhibit non-Gaussian line shapes and decreased line
      widths. These characteristics are engendered by charge migration. We have
      analyzed the temperature dependence of the transport process through EPR spectral
      simulations. The simulations incorporated a nonadiabatic model for electron
      transfer. The temperature dependence could be adequately described on the basis
      of an electron-transfer model that accounts for the effects of slow medium
      relaxation, whereas a satisfactory description could not be obtained on the basis
      of conventional multimode models for transport. The results of our analysis are
      consistent with the notion that the protein functions as the primary solvent for
      the redox centers and are in accord with the view that the protein behaves as a
      frozen glass, even at room temperature, with respect to the low-frequency
      vibrational motions coupled to electron transfer. 

PMID- 26312993
TI  - Bringing Radiotracing to Titanium-Based Antineoplastics: Solid Phase
      Radiosynthesis, PET and ex Vivo Evaluation of Antitumor Agent
      [(45)Ti](salan)Ti(dipic).
AB  - We present a novel solid-phase based (45)Ti radiolabeling methodology and the
      implementation of (45)Ti-PET in titanium-based antineoplastics using the showcase
      compound [(45)Ti](salan)Ti(dipic). This development is intended to allow
      elucidation of the biodistribution and pharmacokinetics of promising new Ti-based
      therapeutics. 

PMID- 26312994
TI  - Room Temperature Single-Photon Emission from Individual Perovskite Quantum Dots.
AB  - Lead-halide-based perovskites have been the subject of numerous recent studies
      largely motivated by their exceptional performance in solar cells. Electronic and
      optical properties of these materials have been commonly controlled by varying
      the composition (e.g., the halide component) and/or crystal structure. Use of
      nanostructured forms of perovskites can provide additional means for tailoring
      their functionalities via effects of quantum confinement and wave function
      engineering. Furthermore, it may enable applications that explicitly rely on the
      quantum nature of electronic excitations. Here, we demonstrate that CsPbX3
      quantum dots (X = I, Br) can serve as room-temperature sources of quantum light,
      as indicated by strong photon antibunching detected in single-dot
      photoluminescence measurements. We explain this observation by the presence of
      fast nonradiative Auger recombination, which renders multiexciton states
      virtually nonemissive and limits the fraction of photon coincidence events to ~6%
      on average. We analyze limitations of these quantum dots associated with
      irreversible photodegradation and fluctuations ("blinking") of the
      photoluminescence intensity. On the basis of emission intensity-lifetime
      correlations, we assign the "blinking" behavior to random charging/discharging of
      the quantum dot driven by photoassisted ionization. This study suggests that
      perovskite quantum dots hold significant promise for applications such as quantum
      emitters; however, to realize this goal, one must resolve the problems of
      photochemical stability and photocharging. These problems are largely similar to
      those of more traditional quantum dots and, hopefully, can be successfully
      resolved using advanced methodologies developed over the years in the field of
      colloidal nanostructures. 

PMID- 26312995
TI  - Novel Small Molecule Agonist of TGR5 Possesses Anti-Diabetic Effects but Causes
      Gallbladder Filling in Mice.
AB  - Activation of TGR5 via bile acids or bile acid analogs leads to the release of
      glucagon-like peptide-1 (GLP-1) from intestine, increases energy expenditure in
      brown adipose tissue, and increases gallbladder filling with bile. Here, we
      present compound 18, a non-bile acid agonist of TGR5 that demonstrates robust GLP
      1 secretion in a mouse enteroendocrine cell line yet weak GLP-1 secretion in a
      human enteroendocrine cell line. Acute administration of compound 18 to mice
      increased GLP-1 and peptide YY (PYY) secretion, leading to a lowering of the
      glucose excursion in an oral glucose tolerance test (OGTT), while chronic
      administration led to weight loss. In addition, compound 18 showed a dose
      dependent increase in gallbladder filling. Lastly, compound 18 failed to show
      similar pharmacological effects on GLP-1, PYY, and gallbladder filling in Tgr5
      knockout mice. Together, these results demonstrate that compound 18 is a mouse
      selective TGR5 agonist that induces GLP-1 and PYY secretion, and lowers the
      glucose excursion in an OGTT, but only at doses that simultaneously induce
      gallbladder filling. Overall, these data highlight the benefits and potential
      risks of using TGR5 agonists to treat diabetes and metabolic diseases. 

PMID- 26312996
TI  - Near Infrared Spectroscopy Facilitates Rapid Identification of Both Young and
      Mature Amazonian Tree Species.
AB  - Precise identification of plant species requires a high level of knowledge by
      taxonomists and presence of reproductive material. This represents a major
      limitation for those working with seedlings and juveniles, which differ
      morphologically from adults and do not bear reproductive structures. Near
      infrared spectroscopy (FT-NIR) has previously been shown to be effective in
      species discrimination of adult plants, so if young and adults have a similar
      spectral signature, discriminant functions based on FT-NIR spectra of adults can
      be used to identify leaves from young plants. We tested this with a sample of 419
      plants in 13 Amazonian species from the genera Protium and Crepidospermum
      (Burseraceae). We obtained 12 spectral readings per plant, from adaxial and
      abaxial surfaces of dried leaves, and compared the rate of correct predictions of
      species with discriminant functions for different combinations of readings. We
      showed that the best models for predicting species in early developmental stages
      are those containing spectral data from both young and adult plants (98% correct
      predictions of external samples), but even using only adult spectra it is still
      possible to attain good levels of identification of young. We obtained an average
      of 75% correct identifications of young plants by discriminant equations based
      only on adults, when the most informative wavelengths were selected. Most species
      were accurately predicted (75-100% correct identifications), and only three had
      poor predictions (27-60%). These results were obtained despite the fact that
      spectra of young individuals were distinct from those of adults when species were
      analyzed individually. We concluded that FT-NIR has a high potential in the
      identification of species even at different ontogenetic stages, and that young
      plants can be identified based on spectra of adults with reasonable confidence. 

PMID- 26312998
TI  - Correction: BNIP3 Regulates AT101 [(-)-Gossypol] Induced Death in Malignant
      Peripheral Nerve Sheath Tumor Cells.

PMID- 26312997
TI  - Intermediate Tyrosyl Radical and Amyloid Structure in Peroxide-Activated
      Cytoglobin.
AB  - We characterized the peroxidase mechanism of recombinant rat brain cytoglobin
      (Cygb) challenged by hydrogen peroxide, tert-butylhydroperoxide and by cumene
      hydroperoxide. The peroxidase mechanism of Cygb is similar to that of myoglobin.
      Cygb challenged by hydrogen peroxide is converted to a Fe4+ oxoferryl pi cation,
      which is converted to Fe4+ oxoferryl and tyrosyl radical detected by direct
      continuous wave-electron paramagnetic resonance and by 3,5-dibromo-4
      nitrosobenzene sulfonate spin trapping. When organic peroxides are used as
      substrates at initial reaction times, and given an excess of peroxide present,
      the EPR signals of the corresponding peroxyl radicals precede those of the direct
      tyrosyl radical. This result is consistent with the use of peroxide as a reducing
      agent for the recycling of Cygb high-valence species. Furthermore, we found that
      the Cygb oxidation by peroxides leads to the formation of amyloid fibrils. This
      result suggests that Cygb possibly participates in the development of
      degenerative diseases; our findings also support the possible biological role of
      Cygb related to peroxidase activity. 

PMID- 26312999
TI  - Drug Authorization for Sofosbuvir/Ledipasvir (Harvoni) for Chronic HCV Infection
      in a Real-World Cohort: A New Barrier in the HCV Care Cascade.
AB  - BACKGROUND: New treatments for hepatitis C (HCV) infection hold great promise for
      cure, but numerous challenges to diagnosing, establishing care, and receiving
      therapy exist. There are limited data on insurance authorization for these
      medications. MATERIALS AND METHODS: We performed a retrospective chart review of
      patients receiving sofosbuvir/ledipasvir (SOF/LED) from October 11-December 31,
      2014 to determine rates and timing of drug authorization. We also determined
      predictors of approval, and those factors associated with faster decision and
      approval times. RESULTS: Of 174 patients prescribed HCV therapy during this
      period, 129 requests were made for SOF/LED, of whom 100 (77.5%) received initial
      approval, and an additional 17 patients (13.9%) ultimately received approval
      through the appeals process. Faster approval times were seen in patients with
      Child-Pugh Class B disease (14.4 vs. 24.7 days, p = 0.048). A higher proportion
      of patients were initially approved in those with Medicare/Medicaid coverage
      (92.2% vs. 71.4%, p = 0.002) and those with baseline viral load >= 6 million
      IU/mL (84.1% vs. 62.5%, p = 0.040). Linear regression modeling identified
      advanced fibrosis, high Model of End Stage Liver Disease (MELD) score, and female
      gender as significant predictors of shorter decision and approval times. On
      logistic regression, Medicare/Medicaid coverage (OR 5.96, 95% CI 1.66-21.48) and
      high viral load (OR 4.52, 95% CI 1.08-19.08) were significant predictors for
      initial approval. CONCLUSIONS: Early analysis of real-world drug authorization
      outcomes between October-December 2014 reveals that nearly one in four patients
      are initially denied access to SOF/LED upon initial prescription, although most
      patients are eventually approved through appeal, which delays treatment
      initiation. Having Medicare/Medicaid and advanced liver disease resulted in a
      higher likelihood of approval as well as earlier decision and approval times.
      More studies are needed to determine factors resulting in higher likelihood of
      denial and to evaluate approval rates and times after implementation of
      restrictive prior authorization guidelines.

PMID- 26313001
TI  - Synthesis, characterisation, and catalytic evaluation of hierarchical faujasite
      zeolites: milestones, challenges, and future directions.
AB  - Faujasite (X, Y, and USY) zeolites represent one of the most widely-applied and
      abundant catalysts and sorbents in the chemical industry. In the last 5 years
      substantial progress was made in the synthesis, characterisation, and catalytic
      exploitation of hierarchically-structured variants of these zeolites. Hererin, we
      provide an overview of these contributions, highlighting the main advancements
      regarding the evaluation of the nature and functionality of introduced secondary
      porosity. The novelty, efficiency, versatility, and sustainability of the
      reported bottom-up and (predominately) top-down strategies are discussed. The
      crucial role of the relative stability of faujasites in aqueous media is
      highlighted. The interplay between the physico-chemical properties of the
      hierarchical zeolites and their use in petrochemical and biomass-related
      catalytic processes is assessed. 

PMID- 26313000
TI  - Effects of Clopidogrel and Proton Pump Inhibitors on Cardiovascular Events in
      Patients with Type 2 Diabetes Mellitus after Drug-Eluting Stent Implantation: A
      Nationwide Cohort Study.
AB  - OBJECTIVE: To investigate whether there is an increased risk of cardiac events in
      diabetic patients with a combined therapy of clopidogrel (CLO) and proton pump
      inhibitors (PPIs) after drug-eluting stent (DES) deployment. METHODS: By using
      National Health Insurance Research Database, all patients who received CLO with
      or without PPI therapy within 90 days after undergoing DES (limus-eluting or
      paclitaxel-eluting stents) deployment were enrolled. Endpoints were acute
      coronary syndrome (ACS) and readmission for revascularization (percutaneous
      coronary intervention or coronary artery bypass graft surgery) after 3, 6, and 12
      months. RESULTS: A total of 6,603 diabetic patients received LESs (5,933 in the
      CLO subgroup and 670 in the CLO plus PPIs subgroup), and 3,202 patients received
      PESs (2,923 in the CLO subgroup and 279 in the CLO plus PPIs subgroup). The
      patients who received CLO plus PPIs were at higher risk of ACS than those
      receiving CLO within 1 year after DES deployment (LESs: 6-month hazard ratio [HR]
      = 1.63, and 1-year HR = 1.37; PESs: 3-month HR = 1.72). Patients with a history
      of ACS who received CLO plus PPIs were at higher risk of ACS after LES
      implantation (HR = 1.55) than those in the CLO group. CONCLUSION: In "real-world"
      diabetic patients with LES deployment, the combination of PPIs and CLO is
      associated with higher rates of ACS after 6 months and 1 year. Even after
      correction for confounding factors, concomitant PPI use remained an independent
      predictor of cardiac events, emphasizing the clinical importance of this drug
      drug interaction.

PMID- 26313002
TI  - Aquaporins Mediate Silicon Transport in Humans.
AB  - In animals, silicon is an abundant and differentially distributed trace element
      that is believed to play important biological functions. One would thus expect
      silicon concentrations in body fluids to be regulated by silicon transporters at
      the surface of many cell types. Curiously, however, and even though they exist in
      plants and algae, no such transporters have been identified to date in
      vertebrates. Here, we show for the first time that the human aquaglyceroporins,
      i.e., AQP3, AQP7, AQP9 and AQP10 can act as silicon transporters in both Xenopus
      laevis oocytes and HEK-293 cells. In particular, heterologously expressed AQP7,
      AQP9 and AQP10 are all able to induce robust, saturable, phloretin-sensitive
      silicon transport activity in the range that was observed for low silicon rice 1
      (lsi1), a silicon transporter in plant. Furthermore, we show that the
      aquaglyceroporins appear as relevant silicon permeation pathways in both mice and
      humans based on 1) the kinetics of substrate transport, 2) their presence in
      tissues where silicon is presumed to play key roles and 3) their transcriptional
      responses to changes in dietary silicon. Taken together, our data provide new
      evidence that silicon is a potentially important biological element in animals
      and that its body distribution is regulated. They should open up original areas
      of investigations aimed at deciphering the true physiological role of silicon in
      vertebrates. 

PMID- 26313003
TI  - Multifactor Regulation of the MdtJI Polyamine Transporter in Shigella.
AB  - The polyamine profile of Shigella, the etiological agent of bacillary dysentery
      in humans, differs markedly from that of E. coli, its innocuous commensal
      ancestor. Pathoadaptive mutations such as the loss of cadaverine and the increase
      of spermidine favour the full expression of the virulent phenotype of Shigella.
      Spermidine levels affect the expression of the MdtJI complex, a recently
      identified efflux pump belonging to the small multi-drug resistance family of
      transporters. In the present study, we have addressed the regulation of the mdtJI
      operon in Shigella by asking which factors influence its expression as compared
      to E. coli. In particular, after identifying the mdtJI promoter by primer
      extension analysis, in vivo transcription assays and gel-retardation experiments
      were carried out to get insight on the silencing of mdtJI in E. coli. The results
      indicate that H-NS, a major nucleoid protein, plays a key role in repressing the
      mdtJI operon by direct binding to the regulatory region. In the Shigella
      background mdtJI expression is increased by the high levels of spermidine
      typically found in this microorganism and by VirF, the plasmid-encoded regulator
      of the Shigella virulence regulatory cascade. We also show that the expression of
      mdtJI is stimulated by bile components. Functional analyses reveal that MdtJI is
      able to promote the excretion of putrescine, the spermidine precursor. This leads
      us to consider the MdtJI complex as a possible safety valve allowing Shigella to
      maintain spermidine to a level optimally suited to survival within infected
      macrophages and, at the same time, prevent toxicity due to spermidine over
      accumulation. 

PMID- 26313005
TI  - Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Treponema
      denticola / Prevotella intermedia Co-Infection Are Associated with Severe
      Periodontitis in a Thai Population.
AB  - Periodontitis is a polymicrobial infection of tooth-supporting tissues. This
      cross-sectional study aimed to examine the associations between five target
      species and severe periodontitis in a Thai population. Using the CDC/AAP case
      definition, individuals diagnosed with no/mild and severe periodontitis were
      included. Quantitative analyses of Aggregatibacter actinomycetemcomitans (Aa),
      Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf), Treponema denticola
      (Td), and Prevotella intermedia (Pi) in subgingival plaque were performed using
      real-time polymerase chain reaction. The association between target species and
      severe periodontitis was examined using logistic regression analysis. The study
      subjects comprised 479 individuals with no/mild periodontitis and 883 with severe
      periodontitis. Bacterial prevalence and quantity were higher in subjects with
      severe periodontitis than in those with no/mild disease. In the fully adjusted
      model, all species except Tf showed a dose-dependent relationship with
      periodontitis. The mere presence of Pg, even in low amount, was significantly
      associated with severe periodontitis, while the amount of Aa, Td, and Pi had to
      reach the critical thresholds to be significantly associated with disease.
      Compared to individuals with low levels of both Td and Pi, high colonization by
      either Td or Pi alone significantly increased the odds of having severe
      periodontitis by 2.5 (95%CI 1.7-3.5) folds. The odds ratio was further increased
      to 14.8 (95%CI 9.2-23.8) in individuals who were highly colonized by both
      species. Moreover, the presence of Pg and high colonization by Aa were
      independently associated with severe periodontitis with odds ratios of 5.6 (95%CI
      3.4-9.1) and 2.2 (95%CI 1.5-3.3), respectively. Our findings suggest that the
      presence of Pg and high colonization by Aa, Td, and Pi play an important role in
      severe periodontitis in this study population. We also demonstrate for the first
      time that individuals co-infected with Td and Pi were more likely to have
      periodontitis than were those infected with a single pathogen. 

PMID- 26313004
TI  - APLP2 Regulates Refractive Error and Myopia Development in Mice and Humans.
AB  - Myopia is the most common vision disorder and the leading cause of visual
      impairment worldwide. However, gene variants identified to date explain less than
      10% of the variance in refractive error, leaving the majority of heritability
      unexplained ("missing heritability"). Previously, we reported that expression of
      APLP2 was strongly associated with myopia in a primate model. Here, we found that
      low-frequency variants near the 5'-end of APLP2 were associated with refractive
      error in a prospective UK birth cohort (n = 3,819 children; top SNP rs188663068,
      p = 5.0 * 10-4) and a CREAM consortium panel (n = 45,756 adults; top SNP
      rs7127037, p = 6.6 * 10-3). These variants showed evidence of differential effect
      on childhood longitudinal refractive error trajectories depending on time spent
      reading (gene x time spent reading x age interaction, p = 4.0 * 10-3).
      Furthermore, Aplp2 knockout mice developed high degrees of hyperopia (+11.5 +/-
      2.2 D, p < 1.0 * 10-4) compared to both heterozygous (-0.8 +/- 2.0 D, p < 1.0 *
      10-4) and wild-type (+0.3 +/- 2.2 D, p < 1.0 * 10-4) littermates and exhibited a
      dose-dependent reduction in susceptibility to environmentally induced myopia
      (F(2, 33) = 191.0, p < 1.0 * 10-4). This phenotype was associated with reduced
      contrast sensitivity (F(12, 120) = 3.6, p = 1.5 * 10-4) and changes in the
      electrophysiological properties of retinal amacrine cells, which expressed Aplp2.
      This work identifies APLP2 as one of the "missing" myopia genes, demonstrating
      the importance of a low-frequency gene variant in the development of human
      myopia. It also demonstrates an important role for APLP2 in refractive
      development in mice and humans, suggesting a high level of evolutionary
      conservation of the signaling pathways underlying refractive eye development. 

PMID- 26313007
TI  - The Identification of Congeners and Aliens by Drosophila Larvae.
AB  - We investigated the role of Drosophila larva olfactory system in identification
      of congeners and aliens. We discuss the importance of these activities in larva
      navigation across substrates, and the implications for allocation of space and
      food among species of similar ecologies. Wild type larvae of cosmopolitan D.
      melanogaster and endemic D. pavani, which cohabit the same breeding sites, used
      species-specific volatiles to identify conspecifics and aliens moving toward
      larvae of their species. D. gaucha larvae, a sibling species of D. pavani that is
      ecologically isolated from D. melanogaster, did not respond to melanogaster odor
      cues. Similar to D. pavani larvae, the navigation of pavani female x gaucha male
      hybrids was influenced by conspecific and alien odors, whereas gaucha female x
      pavani male hybrid larvae exhibited behavior similar to the D. gaucha parent. The
      two sibling species exhibited substantial evolutionary divergence in processing
      the odor inputs necessary to identify conspecifics. Orco (Or83b) mutant larvae of
      D. melanogaster, which exhibit a loss of sense of smell, did not distinguish
      conspecific from alien larvae, instead moving across the substrate. Syn97CS and
      rut larvae of D. melanogaster, which are unable to learn but can smell, moved
      across the substrate as well. The Orco (Or83b), Syn97CS and rut loci are
      necessary to orient navigation by D. melanogaster larvae. Individuals of the
      Trana strain of D. melanogaster did not respond to conspecific and alien larval
      volatiles and therefore navigated randomly across the substrate. By contrast,
      larvae of the Til-Til strain used larval volatiles to orient their movement.
      Natural populations of D. melanogaster may exhibit differences in identification
      of conspecific and alien larvae. Larval locomotion was not affected by the
      volatiles. 

PMID- 26313006
TI  - Small molecule inhibitors of Late SV40 Factor (LSF) abrogate hepatocellular
      carcinoma (HCC): Evaluation using an endogenous HCC model.
AB  - Hepatocellular carcinoma (HCC) is a lethal malignancy with high mortality and
      poor prognosis. Oncogenic transcription factor Late SV40 Factor (LSF) plays an
      important role in promoting HCC. A small molecule inhibitor of LSF, Factor
      Quinolinone Inhibitor 1 (FQI1), significantly inhibited human HCC xenografts in
      nude mice without harming normal cells. Here we evaluated the efficacy of FQI1
      and another inhibitor, FQI2, in inhibiting endogenous hepatocarcinogenesis. HCC
      was induced in a transgenic mouse with hepatocyte-specific overexpression of c
      myc (Alb/c-myc) by injecting N-nitrosodiethylamine (DEN) followed by FQI1 or FQI2
      treatment after tumor development. LSF inhibitors markedly decreased tumor burden
      in Alb/c-myc mice with a corresponding decrease in proliferation and
      angiogenesis. Interestingly, in vitro treatment of human HCC cells with LSF
      inhibitors resulted in mitotic arrest with an accompanying increase in CyclinB1.
      Inhibition of CyclinB1 induction by Cycloheximide or CDK1 activity by Roscovitine
      significantly prevented FQI-induced mitotic arrest. A significant induction of
      apoptosis was also observed upon treatment with FQI. These effects of LSF
      inhibition, mitotic arrest and induction of apoptosis by FQI1s provide multiple
      avenues by which these inhibitors eliminate HCC cells. LSF inhibitors might be
      highly potent and effective therapeutics for HCC either alone or in combination
      with currently existing therapies. 

PMID- 26313008
TI  - Pediatric Immune Thrombocytopenia in Lebanon: Treatment and Predictors of
      Outcome.

PMID- 26313009
TI  - Vapor-Phase Atomic Layer Deposition of Co9S8 and Its Application for
      Supercapacitors.
AB  - Atomic layer deposition (ALD) of cobalt sulfide (Co9S8) is reported. The
      deposition process uses bis(N,N'-diisopropylacetamidinato)cobalt(II) and H2S as
      the reactants and is able to produce high-quality Co9S8 films with an ideal layer
      by-layer ALD growth behavior. The Co9S8 films can also be conformally deposited
      into deep narrow trenches with aspect ratio of 10:1, which demonstrates the high
      promise of this ALD process for conformally coating Co9S8 on high-aspect-ratio 3D
      nanostructures. As Co9S8 is a highly promising electrochemical active material
      for energy devices, we further explore its electrochemical performance by
      depositing Co9S8 on porous nickel foams for supercapacitor electrodes. Benefited
      from the merits of ALD for making high-quality uniform thin films, the ALD
      prepared electrodes exhibit remarkable electrochemical performance, with high
      specific capacitance, great rate performance, and long-term cyclibility, which
      highlights the broad and promising applications of this ALD process for energy
      related electrochemical devices, as well as for fabricating complex 3D
      nanodevices in general. 

PMID- 26313011
TI  - How close are PDE5 inhibitors to being successful in the treatment of BPH?

PMID- 26313010
TI  - Glucosylceramides are critical for cell-type differentiation and organogenesis,
      but not for cell viability in Arabidopsis.
AB  - Glucosylceramides (GlcCer), glucose-conjugated sphingolipids, are major
      components of the endomembrane system and plasma membrane in most eukaryotic
      cells. Yet the quantitative significance and cellular functions of GlcCer are not
      well characterized in plants and other multi-organ eukaryotes. To address this,
      we examined Arabidopsis lines that were lacking or deficient in GlcCer by
      insertional disruption or by RNA interference (RNAi) suppression of the single
      gene for GlcCer synthase (GCS, At2g19880), the enzyme that catalyzes GlcCer
      synthesis. Null mutants for GCS (designated 'gcs-1') were viable as seedlings,
      albeit strongly reduced in size, and failed to develop beyond the seedling stage.
      Heterozygous plants harboring the insertion allele exhibited reduced transmission
      through the male gametophyte. Undifferentiated calli generated from gcs-1
      seedlings and lacking GlcCer proliferated in a manner similar to calli from wild
      type plants. However, gcs-1 calli, in contrast to wild-type calli, were unable to
      develop organs on differentiation media. Consistent with a role for GlcCer in
      organ-specific cell differentiation, calli from gcs-1 mutants formed roots and
      leaves on media supplemented with the glucosylated sphingosine glucopsychosine,
      which was readily converted to GlcCer independent of GCS. Underlying these
      phenotypes, gcs-1 cells had altered Golgi morphology and fewer cisternae per
      Golgi apparatus relative to wild-type cells, indicative of protein trafficking
      defects. Despite seedling lethality in the null mutant, GCS RNAi suppression
      lines with <=2% of wild-type GlcCer levels were viable and fertile. Collectively,
      these results indicate that GlcCer are essential for cell-type differentiation
      and organogenesis, and plant cells produce amounts of GlcCer in excess of that
      required for normal development. 

PMID- 26313012
TI  - Ligand-Enabled Meta-C-H Alkylation and Arylation Using a Modified Norbornene.
AB  - 2-Carbomethoxynorbornene is identified as a more effective transient mediator to
      promote a Pd(II)-catalyzed meta-C(sp(2))-H alkylation of amides with various
      alkyl iodides as well as arylation with previously incompatible aryl iodides. The
      use of a tailor-made quinoline ligand is also crucial for this reaction to
      proceed. 

PMID- 26313013
TI  - The influence of headaches in patients with chronic dizziness.
AB  - CONCLUSION: The frequency of headaches in patients complaining of chronic
      dizziness is closely related to the severity of the dizziness impairments and
      mood states, such as anxiety. It is, therefore, important to treat co-morbid
      headache in patients with chronic dizziness. The severity of the dizziness
      impairments and other mood states, including anxiety, did not differ between
      patients with migraine or non-migraine headaches. OBJECTIVES: Patients with
      chronic dizziness often complain of headaches or general fatigue. This study
      investigated the influence of the frequency of headaches on dizziness
      impairments, anxiety, quality-of-life, and other mood states in patients with
      chronic dizziness. METHOD: The subjects consisted of 100 consecutive patients
      with intractable dizziness. Several types of questionnaires were used in the
      investigations. RESULTS: Of the 85 patients, 51 had either type of headache
      (tension headache, 38; migraine, 13). The total score on the Dizziness Handicap
      Inventory correlated linearly with general fatigue (R = 0.39, p < 0.001) and
      headache (R = 0.25, p < 0.05). The patients with any type of headache had a
      significantly more positive family history of headache (p < 0.05).

PMID- 26313014
TI  - Methylation of tissue factor pathway inhibitor 2 as a prognostic biomarker for
      hepatocellular carcinoma after hepatectomy.
AB  - BACKGROUND AND AIM: Methylation of tissue factor pathway inhibitor 2 (TFPI2) gene
      has been detected in hepatocellular carcinoma (HCC). However, the
      clinicopathologcial significance and prognostic value of TFPI2 methylation in HCC
      remains largely unknown. This study aimed to investigate the prognostic value of
      TFPI2 methylation in HCC after hepatectomy. METHODS: Methylation status of TFPI2
      gene was examined in 178 surgical specimens of HCC and 20 normal liver samples
      using methylation-specific polymerase chain reaction. RESULTS: Methylation of
      TFPI2 gene was detected in 44.9% (80 of 178) of primary HCC samples, 10.7% (19 of
      178) of the corresponding non-tumorous liver samples, and 5.0% (1/20) of the
      normal liver samples. The mRNA concentrations of TFPI2 in primary HCC tissues
      were significantly lower than those in corresponding non-tumorous liver tissues
      and those in normal liver tissues. TFPI2 methylation was significantly associated
      with higher TNM stage. Patients with TFPI2 methylation demonstrated a
      significantly poorer prognosis than those without TFPI2 methylation for both
      overall survival and disease-free survival (P < 0.001, respectively).
      Multivariate analyses confirmed that TFPI2 methylation was an independent
      prognostic factor for both overall survival (P = 0.002) and disease-free survival
      (P = 0.000) in HCC after hepatectomy. Moreover, TFPI2 methylation was found to be
      the only independent predictor for early tumor recurrence of HCC after resection
      based on multivariate analysis (P = 0.002). CONCLUSIONS: Methylation of TFPI2
      predicts high risk of advanced tumor stage, early tumor recurrence, and poor
      prognosis, and it could be a potential prognostic biomarker in patients with HCC
      after hepatectomy.

PMID- 26313016
TI  - Professionalism and the environment: The influence of role models.

PMID- 26313015
TI  - Association of DC-SIGNR Expression in Peripheral Blood Mononuclear Cells with DC
      SIGNR Genotypes in HIV-1 Infection.
AB  - Dendritic cell-specific intracellular adhesion molecule 3 grabbing nonintegrin
      related molecule (DC-SIGNR) is a C-type lectin, calcium-dependent carbohydrate
      binding protein, which can act as a cell-adhesion and pathogen recognition
      receptor. DC-SIGNR is known to be highly expressed on liver sinusoidal cells and
      in the lymph nodes. However, its expression in peripheral blood mononuclear cells
      (PBMCs) in HIV-1 infection has not been addressed. Therefore, this study
      determined the expression of DC-SIGNR in PBMCs of HIV-1-infected patients and
      healthy seronegative individuals by real-time polymerase chain reaction and
      assessed its correlation with CD4+ T cell counts and DC-SIGNR genotypes. A
      significantly higher expression of DC-SIGNR was observed in the PBMCs of HIV-1
      infected patients compared with healthy seronegative individuals. Further, there
      was a negative correlation between DC-SIGNR expression and CD4+ T cell counts and
      positive with viral load, with higher DC-SIGNR expression in the PBMCs of HIV-1
      infected patients with a CD4+ T cell count <200 cells/MUL than those with >200
      cells/MUL. This is the first study to report the expression of DC-SIGNR in PBMCs
      of HIV-1-infected patients. A salient finding of this study is that the DC-SIGNR
      expression was higher in HIV-1-infected patients, and its positive correlation
      with viral load and negative with CD4+ T cells counts suggesting a potential role
      of DC-SIGNR in HIV-1 infection. 

PMID- 26313017
TI  - Clinical Comparison of Platelet-Rich Fibrin and a Gelatin Sponge in the
      Management of Palatal Wounds After Epithelialized Free Gingival Graft Harvest: A
      Randomized Clinical Trial.
AB  - BACKGROUND: Platelet-rich fibrin (PRF) promotes tissue regeneration by releasing
      various growth factors. The palatal donor site of the epithelialized connective
      tissue (CT) graft significantly influences the patient's morbidity. The aim of
      this study is to compare the effects of PRF and gelatin sponge on the healing of
      palatal donor sites and the patient's morbidity. METHODS: Forty patients with at
      least one site of Miller Class I or II gingival recession were treated by a
      coronally advanced flap with CT graft resulting from the de-epithelialization of
      a free gingival graft. In the test group (20 patients), a PRF membrane was placed
      over the palatal wounds; conversely, the 20 control group patients were treated
      with an absorbable gelatin sponge. Patients were monitored at 1, 2, 3, and 4
      weeks after surgery for the complete re-epithelialization of the palatal wound
      (CWE), the alteration of sensitivity around the wound area, postoperative
      discomfort, and changes in feeding habits (CFH). Furthermore, the consumption of
      analgesics during the postoperative week 1 was assessed. RESULTS: The test group
      showed a significantly faster CWE (P <0.001); 35% of the test patients showed CWE
      at the end of week 2 (controls, 10%), whereas at the end of week 3, all palatal
      wounds in the test patients epithelialized completely (controls, 25%). Similarly,
      test patients reported significantly less discomfort and CFH (P <= 0.02) and took
      a significantly lower dose of analgesics (P = 0.02). CONCLUSION: The PRF-enriched
      palatal bandage significantly accelerates palatal wound healing and reduces the
      patient's morbidity.

PMID- 26313018
TI  - Salivary Lipid Peroxidation in Patients With Generalized Chronic Periodontitis
      and Acute Coronary Syndrome.
AB  - BACKGROUND: Lipid peroxidation is a major consequence of oxidative stress and can
      be evaluated via malondialdehyde (MDA) levels. The present study aims to assess
      MDA levels in the saliva of patients with chronic periodontitis (CP) and acute
      coronary syndrome (ACS) and establish their correlation with periodontal clinical
      parameters, serum high-sensitivity C-reactive protein (hsCRP), and plasma
      fibrinogen. METHODS: The study enrolled 64 patients stratified into four age- and
      sex-matched groups: both ACS and CP, ACS only, CP only, and healthy controls. All
      patients were examined, periodontal clinical parameters were recorded, and saliva
      and blood samples were collected. Salivary MDA levels were measured using a
      spectrophotometric assay. A quantitative turbidimetric test was used for the
      measurement of serum hsCRP levels, and plasma fibrinogen levels were determined
      using an automated analyzer. RESULTS: Salivary MDA levels were significantly
      higher in patients with both ACS and CP than in those with only ACS or only CP
      and healthy controls (P <0.05). There were significant positive correlations
      between salivary MDA levels and periodontal clinical parameters as well as
      biomarkers for cardiovascular events (P <0.001). CONCLUSIONS: To our knowledge,
      this study is the first to investigate salivary MDA levels in patients with ACS
      and their correlations with serum hsCRP and plasma fibrinogen levels. The results
      indicate that salivary MDA levels could be a biomarker for cardiovascular and/or
      periodontal disease.

PMID- 26313019
TI  - Systematic Review of Soft Tissue Alterations and Esthetic Outcomes Following
      Immediate Implant Placement and Restoration of Single Implants in the Anterior
      Maxilla.
AB  - BACKGROUND: The aim of this review is to assess the outcome of single-tooth
      immediate implant placement and restoration (IPR) in the maxillary anterior
      region, with a particular emphasis on soft tissue and esthetic outcomes. METHODS:
      An electronic search in Medline, EBSCOhost, and Ovid (PubMed) was performed to
      identify studies that reported on soft tissue outcomes following immediate
      placement and restoration of implants in the maxillary esthetic region with a
      mean follow-up of >=1 year. RESULTS: Nineteen studies on single implants inserted
      immediately into fresh extraction sockets and provisionally restored in the
      maxillary esthetic region were included. Soft tissue changes were found to be
      acceptable, with most studies reporting mean gingival recession of 0.27 +/- 0.38
      mm and mean papillary height loss of 0.23 +/- 0.27 mm after follow-up of >=1
      year. Advanced buccal recession (>1 mm) occurred in 11% of cases. Long-term
      follow-up studies (>2 years) reported that the interdental papillae, in
      particular, showed a tendency to rebound over time. The few studies that reported
      on patient-centered outcomes showed a high level of patient satisfaction with the
      outcomes of IPR treatment. CONCLUSIONS: The IPR protocol resulted in generally
      acceptable soft tissue and esthetic outcomes, with suboptimal results reported in
      ~11% of low-risk cases. Factors such as preoperative tissue biotype or use of a
      flap or connective tissue graft did not significantly influence soft tissue and
      esthetic outcomes. Long-term prospective controlled clinical trials are necessary
      to identify factors that may influence the esthetic outcomes associated with IPR.

PMID- 26313020
TI  - Evaluation of MicroRNA-146a and Its Targets in Gingival Tissues of Patients With
      Chronic Periodontitis.
AB  - BACKGROUND: MicroRNAs (miRNAs) are a group of small non-coding RNAs that play an
      important role in the regulation of gene expression. miRNA-146a (miR-146a), a
      member of the miR-146 family, is involved in the control of inflammation.
      Periodontitis is a set of chronic inflammatory disorders of the tissues
      surrounding the teeth that lead to the breakdown of alveolar bone and tooth loss.
      In this study, expression levels of miR-146a and its targets, including tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6, are evaluated in
      human patients with chronic periodontitis (CP). METHODS: The study population
      consisted of 10 healthy controls and 20 individuals with CP. For each
      participant, clinical parameters including probing depth and clinical attachment
      level were measured, and a gingival tissue sample was collected. Levels of miR
      146a, TNF-alpha, IL-1beta, and IL-6 were quantified using real-time polymerase
      chain reaction. RESULTS: Levels of miR-146a were significantly higher in patients
      with CP (P <0.001). There was a positive correlation between levels of miR-146a
      and clinical parameters (P <0.05). Elevated miR-146a was accompanied by a
      significant reduction in TNF-alpha and IL-6 (P <0.001). CONCLUSIONS: Patients
      with CP had higher levels of miR-146a than healthy individuals, accompanied by
      reduced levels of TNF-alpha and IL-6. A positive relationship between miR-146a
      levels and clinical parameters suggests a pathophysiologic role of miR-146a in
      CP.

PMID- 26313021
TI  - Precision Medicine in Breast Cancer Care: An Early Glimpse of Impact.

PMID- 26313022
TI  - Recruitment Pattern in a Complete Cerebral Arterial Circle.
AB  - Blood flow through a vessel depends upon compliance and resistance. Resistance
      changes dynamically due to vasoconstriction and vasodilation as a result of
      metabolic activity, thus allowing for more or less flow to a particular area. The
      structure responsible for directing blood to the different areas of the brain and
      supplying the increase flow is the cerebral arterial circle (CAC). A series of 1D
      equations were utilized to model propagating flow and pressure waves from the
      left ventricle of the heart to the CAC. The focus of the current research was to
      understand the collateral capability of the circle. This was done by decreasing
      the peripheral resistance in each of the efferent arteries, up to 10% both
      unilaterally and bilaterally. The collateral patterns were then analyzed. After
      the initial 60 simulations, it became apparent that flow could increase beyond
      the scope of a 10% reduction and still be within in vivo conditions. Simulations
      with higher percentage decreases were performed such that the same amount of flow
      increase would be induced through each of the efferent arteries separately, same
      flow tests (SFTs), as well as those that were found to allow for the maximum flow
      increase through the stimulated artery, maximum flow tests (MFTs). The collateral
      pattern depended upon which efferent artery was stimulation and if the
      stimulation was unilaterally or bilaterally induced. With the same amount of flow
      increase through each of the efferent arteries, the MCAs (middle cerebral
      arteries) had the largest impact on the collateral capability of the circle, both
      unilaterally and bilaterally. 

PMID- 26313023
TI  - Levels of Acculturation of Chinese Older Adults in the Greater Chicago Area - The
      Population Study of Chinese Elderly in Chicago.
AB  - Acculturation is a difficult process for minority older adults for a variety of
      reasons, including access and exposure to mainstream culture, competing ethnic
      identities, and linguistic ability and preference. There is a paucity of research
      regarding overall level of acculturation for Chinese older adults in the United
      States. This study aimed to provide an overall estimate of level of acculturation
      of Chinese older adults in the United States and to examine correlations between
      sociodemographic characteristics, self-reported health measures, and level of
      acculturation. Data were collected through the Population Study of Chinese
      Elderly in Chicago (PINE) study. This community-based participatory research
      study surveyed 3,159 Chinese older adults aged 60 and older. The PINE Study
      Acculturation Scale was used to assess level of acculturation in three
      dimensions: language preference, media use, and ethnic social relations. Mean
      acculturation level for all items was 15.3 +/- 5.1, indicating low levels of
      acculturation. Older age, more offspring, lower income, fewer years living in the
      United States, lower overall health status, and lower quality of life were
      associated with lower levels of acculturation. Level of acculturation was low in
      Chinese older adults, and certain subsets of the population were more likely to
      have a lower level of acculturation. Future research should investigate causality
      and effects of level of acculturation.

PMID- 26313024
TI  - A novel preparation of core-shell electrode materials via evaporation-induced
      self-assembly of nanoparticles for advanced Li-ion batteries.
AB  - We report, for the first time, a simple and novel synthesis of a Li-rich layered
      spinel core-shell heterostructure (L@S core-shell) via evaporation-induced self
      assembly (EISA) of Ni-doped Li4Mn5O12 nanoparticles (Li4Mn4.5Ni0.5O12) onto the
      surface of layered Li[Li0.2Mn0.54Ni0.13Co0.13]O2 (LMNCO) without using any
      surfactant during the coating process. The resultant L@S core-shell as a cathode
      in lithium ion batteries demonstrates significantly improved specific capacity,
      cycling performance and rate capability compared to pristine LMNCO. 

PMID- 26313025
TI  - Short-term beat-to-beat variability of the QT interval is increased and
      correlates with parameters of left ventricular hypertrophy in patients with
      hypertrophic cardiomyopathy.
AB  - Stratification models for the prediction of sudden cardiac death (SCD) are
      inappropriate in patients with hypertrophic cardiomyopathy (HCM). We investigated
      conventional electrocardiogram (ECG) repolarization parameters and the beat-to
      beat short-term QT interval variability (QT-STV), a new parameter of
      proarrhythmic risk, in 37 patients with HCM (21 males, average age 48 +/- 15
      years). Resting ECGs were recorded for 5 min and the frequency corrected QT
      interval (QTc), QT dispersion (QTd), beat-to-beat short-term variability of QT
      interval (QT-STV), and the duration of terminal part of T waves (Tpeak-Tend) were
      calculated. While all repolarization parameters were significantly increased in
      patients with HCM compared with the controls (QTc, 488 +/- 61 vs. 434 +/- 23 ms,
      p < 0.0001; QT-STV, 4.5 +/- 2 vs. 3.2 +/- 1 ms, p = 0.0002; Tpeak-Tend duration,
      107 +/- 27 vs. 91 +/- 10 ms, p = 0.0015; QTd, 47 +/- 17 vs. 34 +/- 9 ms, p =
      0.0002), QT-STV had the highest relative increase (+41%). QT-STV also showed the
      best correlation with indices of left ventricular (LV) hypertrophy, i.e., maximal
      LV wall thickness normalized for body surface area (BSA; r = 0.461, p = 0.004) or
      LV mass (determined by cardiac magnetic resonance imaging) normalized for BSA (r
      = 0.455, p = 0.015). In summary, beat-to-beat QT-STV showed the most marked
      increase in patients with HCM and may represent a novel marker that merits
      further testing for increased SCD risk in HCM. 

PMID- 26313026
TI  - The Significance and Therapeutic Potential of GATA3 Expression and Mutation in
      Breast Cancer: A Systematic Review.
AB  - GATA3 is a critical transcription factor in the development of various human
      systems. The notion that GATA3 expression is required for the differentiation and
      maintenance of normal breast tissue has been well established. Recently, GATA3 is
      found to actively participate in the multistep process leading breast cancer
      pathogenesis, including tumorigenesis, tumor differentiation, epithelial
      mesenchymal transition, and metastasis through regulation of various target
      genes. On the other hand, several studies have raised questions and highlighted
      the role of GATA3-low or GATA3-negative cells during the malignant development of
      breast cancer. In addition to gene expression, GATA3 mutations provide another
      dimension of complexity. As one of the most frequently mutated genes in breast
      cancer, GATA3 mutations may have an effect on DNA-binding ability, protein
      production, and transactivation activity. Recognition of the multiple function of
      GATA3 in breast cancer will serve to deepen our understanding of the nature of
      this disease and develop novel therapeutic approaches. 

PMID- 26313027
TI  - Nanomanufacturing of 2D Transition Metal Dichalcogenide Materials Using Self
      Assembled DNA Nanotubes.
AB  - 2D transition metal dichalcogenides (TMDCs) are nanomanufactured using a
      generalized strategy with self-assembled DNA nanotubes. DNA nanotubes of various
      lengths serve as lithographic etch masks for the dry etching of TMDCs. The
      nanostructured TMDCs are studied by atomic force microscopy, photoluminescence,
      and Raman spectroscopy. This parallel approach can be used to manufacture 2D TMDC
      nanostructures of arbitrary geometries with molecular-scale precision. 

PMID- 26313028
TI  - In Response: Quantitative adverse outcome pathways for prediction of adverse
      effects--An academic perspective.

PMID- 26313029
TI  - The Challenge: Adverse outcome pathways in research and regulation--Current
      status and future perspectives.

PMID- 26313030
TI  - In Response: Adverse outcome pathways--An industry perspective.

PMID- 26313031
TI  - In Response: The path forward for the adverse outcome pathway framework--A
      regulatory perspective.

PMID- 26313032
TI  - Letters to the Editor.

PMID- 26313033
TI  - The author's reply.

PMID- 26313035
TI  - Characterization of human organ donors testing positive for type 1 diabetes
      associated autoantibodies.
AB  - In this study we aim to describe the characteristics of non-diabetic organ donors
      with circulating diabetes-associated autoantibodies collected within the Nordic
      Network for Islet Transplantation. One thousand and thirty organ donors have been
      screened in Uppsala for antibodies against glutamic acid decarboxylase (GADA) and
      islet antigen-2 (IA-2A). The 32 non-diabetic donors that tested positive for GADA
      (3.3% of all non-diabetic donors) were studied in more detail, together with 32
      matched controls. Mean age among the autoantibody-positive donors was 52.6 (range
      21-74), family history of type 1 diabetes (T1D) was unknown, and no donor was
      genetically predisposed for T1D regarding the human leucocyte antigen (HLA)
      locus. Subjects were analysed for islet cell antibodies (ICA), insulin
      autoantibodies (IAA) and zinc transporter 8 antibodies (ZnT8A), and pancreas
      morphology and clinical data were examined. Eight non-diabetic donors tested
      positive for two antibodies and one donor tested positive for four antibodies. No
      insulitis or other signs of a diabetic process were found in any of the donors.
      While inflammatory cells were present in all donors, subjects with high GADA
      titres had significantly higher CD45 cell numbers in exocrine tissue than
      controls. The extent of fibrosis was more pronounced in autoantibody-positive
      donors, even in subjects with lower GADA titres. Notably, it is possible that
      events not related directly to T1D (e.g. subclinical pancreatitis) may induce
      autoantibodies in some cases.

PMID- 26313036
TI  - Mycophenolic Acid Metabolites Acyl-Glucuronide and Glucoside Affect the
      Occurrence of Infectious Complications and Bone Marrow Dysfunction in Liver
      Transplant Recipients.
AB  - BACKGROUND Mycophenolic acid (MPA) prodrugs are anti-proliferative
      immunosuppressive agents commonly used after organ transplantation. Although they
      are generally well tolerated by patients, adverse effects may occur. It is
      postulated that MPA metabolites could also contribute to these adverse effects.
      MATERIAL AND METHODS The objective of this study was the assessment of
      concentrations of total MPA and its metabolites, phenyl glucuronide (MPAG), acyl
      glucuronide (AcMPAG) and glucoside (GluMPA), using liquid chromatography combined
      with mass spectrometry (LC/MS/MS) in two groups: kidney transplant recipients and
      liver transplant patients. Associations of MPA and its metabolites with adverse
      effects were analyzed. RESULTS The study group consisted of 211 recipients of
      liver or kidney transplants who received immunosuppressive therapy, including MPA
      prodrugs. Multivariant analysis showed a positive influence of MPA on
      gastroenterotoxicity in kidney transplant recipients. In liver patients,
      gastroenterotoxicity was associated with lower MPAG concentrations. A positive
      influence of AcMPAG on bacterial infections in liver transplant patients was
      observed. In liver transplant recipients, a positive influence of MPA and a
      negative influence of GluMPA levels on the PLT count were revealed. MPA and its
      metabolites did not influence the hemoglobin levels in both groups. There were no
      significant relationships among MPA, its metabolites and WBC counts. CONCLUSIONS
      In kidney transplant recipients, total MPA trough concentration is associated
      with gastroenterotoxicity and its monitoring could have important role in
      management of gastrointestinal complications. The quantification of AcMPAG in
      liver recipients receiving MPA may be helpful in avoiding bacterial infections.
      GluMPA seems to have a toxic effect on thrombopoiesis. 

PMID- 26313037
TI  - Cognitive impairment and gray matter volume abnormalities in silent cerebral
      infarction.
AB  - To investigate the association between cognitive impairment and gray matter
      volume (GMV) abnormalities in silent cerebral infarction (SCI) patients, the GMV
      of 62 pairs of patients and well-matched healthy controls was calculated. All
      participants underwent a P300 test, a Montreal Cognitive Assessment (MoCA) test.
      Compared with controls, the patients showed decreased GMV in the left superior
      frontal gyrus, left inferior frontal gyrus, left superior temporal gyrus, right
      middle temporal gyrus, and bilateral parahippocampal gyrus; no significantly
      increasing GMV was found. The volumes of the frontal and temporal lobes were
      positively correlated with the score of the MoCA scale and P300 amplitudes
      (r>=0.62, P<0.01). The P300 latency was negatively correlated with the volumes of
      the frontal lobe, the temporal lobe, and the hippocampus (r<=-0.71, P<0.05). No
      significant correlations between the GMV of the abnormal brain regions and four
      clinical characteristics in SCI patients were found, suggesting that cognitive
      deficiency existed in SCI patients and the reduced GMV might contribute to the
      pathology of cognitive deficiency in SCI patients.

PMID- 26313038
TI  - Bipolar Spectrum Disorders in Patients With Cerebellar Lesions: A Comparison With
      Parkinson's Disease.
AB  - Nonmotor functions of the cerebellum are well known. Within this frame, the aim
      of this study was to compare psychiatric morbidity rates among patients affected
      by cerebellar diseases or Parkinson's disease (PD). Forty-seven patients (27
      cerebellar and 20 PD) underwent a comprehensive psychiatric evaluation
      (psychopathological rating scales and the Structured Clinical Interview for DSM
      IV-TR Axis I Disorders). Psychiatric disorders were slightly more frequent among
      cerebellar than among PD patients (89% vs. 75%; p = 0.21). Mood disorders were
      more frequent in the cerebellar than in the PD group (90% vs. 55%; p < 0.01).
      Among those subjects with no psychiatric history prior to the onset of
      neurological disease, bipolar spectrum disorders were more frequent within the
      cerebellar group (p < 0.01). These results confirm high rates of psychiatric
      disorders among cerebellar patients. The higher frequency of bipolar spectrum
      presentations found in the cerebellar group may suggest a specific involvement of
      cortico-cerebellar circuits in the pathophysiology of mood dysregulation. 

PMID- 26313039
TI  - Group Psychoeducation for Relatives of Persons With Bipolar Disorder: Perceived
      Benefits for Participants and Patients.
AB  - Psychoeducation is a key element in the management of patients with bipolar
      disorders. The present study explored the perception of patients and family
      members with respect to group psychoeducation for relatives. Patients (n = 20)
      and relatives (n = 26) were assessed with questionnaires about perceived benefits
      and quality of life (median 4 years after participation). A large majority (>80%)
      of relatives acknowledged benefits with respect to easier detection of the early
      warning signs of relapse, improved quality of life, feeling more involved, and
      engaging in higher quality caregiving activities. Patients were less positive in
      general, but agreed that the program had helped them deal with crises, increased
      their feeling of being understood by relatives, and promoted positive changes in
      the family (>60%). Perceived positive changes in the family were associated with
      higher quality of life for relatives and patients. The present study highlights
      the importance of communication enhancement in group psychoeducation for
      relatives. 

PMID- 26313040
TI  - Psychotherapy for Personality Disorders in a Natural Setting: A Pilot Study over
      Two Years of Treatment.
AB  - Long-term assessment of the effects of psychotherapy for personality disorders
      (PDs) in a natural environment is an important task. Such research contributes to
      enlarge the practice-based evidence, embedded in broad collaborations between
      clinicians and researchers in psychotherapy for PDs. The present pilot study used
      rigorous assessment procedures and incorporated feedback loops of outcome
      information to the therapists in demonstrating the effects of psychotherapy for
      PD in a natural setting. The number of Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition (DSM-IV), criteria for any PD was the primary
      outcome (along with psychological distress, depression, impulsiveness, and
      quality of life as secondary measures), assessed at intake, 6, 12, 18, and 24
      months of psychotherapy for N = 13 patients with PD. Data were analyzed using
      hierarchical linear modeling. Results demonstrated a large pre-post effect (d =
      2.22) for the observer-rated measure (primary outcome), and small to medium
      effects for the secondary outcomes; these results were corroborated by a steady
      decrease of symptoms over all five time points, which was significant for several
      outcomes. These results add a piece to the literature by demonstrating the
      effects of long-term psychotherapy for PDs in increasingly diverse contexts and
      suggest that practice-oriented research can be carried out in a collaborative and
      systematic manner. 

PMID- 26313042
TI  - "In Spanish": advancing public health.

PMID- 26313044
TI  - Public health and Cuba: trading on a two-way street.

PMID- 26313048
TI  - The combined effects of the expansion of primary health care and conditional cash
      transfers on infant mortality in Brazil, 1998-2010.
AB  - OBJECTIVES: I examined the combined effects of access to primary care through the
      Family Health Program (FHP) and conditional cash transfers from the Bolsa Familia
      Program (BFP) on postneonatal infant mortality (PNIM) in Brazil. METHODS: I
      employed longitudinal ecological analysis using panel data from 4583 Brazilian
      municipalities from 1998 to 2010, totaling 54 253 observations. I estimated fixed
      effects ordinary least squares regressions models with PNIM rate as the dependent
      variable and FHP, BFP, and their interactions as the main independent variables
      of interest. RESULTS: The association of higher FHP coverage with lower PNIM
      became stronger as BFP coverage increased. At the means of all other variables,
      when BFP coverage was 25%, predicted PNIM was 5.24 (95% confidence interval [CI]
      = 4.95, 5.53) for FHP coverage = 0% and 3.54 (95% CI = 2.77, 4.31) for FHP
      coverage = 100%. When BFP coverage was 60%, predicted PNIM was 4.65 (95% CI =
      4.36, 4.94) when FHP coverage = 0% and 1.38 (95% CI = 0.88, 1.89) when FHP
      coverage = 100%. CONCLUSIONS: The effect of the FHP depends on the expansion of
      the BFP. For impoverished, underserved populations, combining supply- and demand
      side interventions may be necessary to improve health outcomes.

PMID- 26313046
TI  - Explaining racial disparities in infant health in Brazil.
AB  - OBJECTIVES: We sought to quantify how socioeconomic, health care, demographic,
      and geographic effects explain racial disparities in low birth weight (LBW) and
      preterm birth (PTB) rates in Brazil. METHODS: We employed a sample of 8949
      infants born between 1995 and 2009 in 15 cities and 7 provinces in Brazil. We
      focused on disparities in LBW (< 2500 g) and PTB (< 37 gestational weeks)
      prevalence between infants of African ancestry alone or African mixed with other
      ancestries, and European ancestry alone. We used a decomposition model to
      quantify the contributions of conceptually relevant factors to these disparities.
      RESULTS: The model explained 45% to 94% of LBW and 64% to 94% of PTB disparities
      between the African ancestry groups and European ancestry. Differences in
      prenatal care use and geographic location were the most important contributors,
      followed by socioeconomic differences. The model explained the majority of the
      disparities for mixed African ancestry and part of the disparity for African
      ancestry alone. CONCLUSIONS: Public policies to improve children's health should
      target prenatal care and geographic location differences to reduce health
      disparities between infants of African and European ancestries in Brazil.

PMID- 26313050
TI  - Effectiveness of border screening for detecting influenza in arriving airline
      travelers.
AB  - OBJECTIVES: We measured symptom and influenza prevalence, and the effectiveness
      of symptom and temperature screening for identifying influenza, in arriving
      international airline travelers. METHODS: This cross-sectional study collected
      data from travelers to Christchurch International Airport, New Zealand, in winter
      2008, via a health questionnaire, temperature testing, and respiratory sampling.
      RESULTS: Forms were returned by 15 976 (68%) travelers. Of these, 17% reported at
      least 1 influenza symptom, with runny or blocked nose (10%) and cough (8%) most
      common. Respiratory specimens were obtained from 3769 travelers. Estimated
      prevalence of influenza was 1.1% (4% among symptomatic, 0.2% among asymptomatic).
      The sensitivity of screening criteria ranged from 84% for "any symptom" to 3% for
      a fever of 37.8  degrees C or greater. The positive predictive value was low for
      all criteria. CONCLUSIONS: Border screening using self-reported symptoms and
      temperature testing has limitations for preventing pandemic influenza from
      entering a country. Using "any symptom" or cough would lead to many uninfected
      people being investigated, yet some infected people would remain undetected. If
      more specific criteria such as fever were used, most infected people would enter
      the country despite screening.

PMID- 26313052
TI  - Preparedness for natural disasters among older US adults: a nationwide survey.
AB  - OBJECTIVES: We sought to determine natural disaster preparedness levels among
      older US adults and assess factors that may adversely affect health and safety
      during such incidents. METHODS: We sampled adults aged 50 years or older (n =
      1304) from the 2010 interview survey of the Health and Retirement Study. The
      survey gathered data on general demographic characteristics, disability status or
      functional limitations, and preparedness-related factors and behaviors. We
      calculated a general disaster preparedness score by using individual indicators
      to assess overall preparedness. RESULTS: Participant (n = 1304) mean age was 70
      years (SD = 9.3). Only 34.3% reported participating in an educational program or
      reading materials about disaster preparation. Nearly 15% reported using
      electrically powered medical devices that might be at risk in a power outage. The
      preparedness score indicated that increasing age, physical disability, and lower
      educational attainment and income were independently and significantly associated
      with worse overall preparedness. CONCLUSIONS: Despite both greater vulnerability
      to disasters and continuous growth in the number of older US adults, many of the
      substantial problems discovered are remediable and require attention in the
      clinical, public health, and emergency management sectors of society.

PMID- 26313053
TI  - Labor and neonatal outcomes after term induction of labor in gestational
      diabetes.
AB  - OBJECTIVE: To identify the optimal gestational age (GA) for induction of labor
      (IOL) at term among patients with gestational diabetes (GDMA) according to
      perinatal outcomes. STUDY DESIGN: The US Natality Database from 2007 to 2010 was
      reviewed. Inclusion criteria were singleton delivery, IOL at 37 to 42 weeks and
      GDMA. Exclusion criteria included congenital anomalies, pre-gestational diabetes,
      hypertensive disorders, previous cesarean, breech presentation and rupture of
      membranes. Controls were non-GDMA cases delivered in geographic and temporal
      proximity. Delivery mode, macrosomia and perinatal complications were analyzed.
      Logistic regression adjusted for confounders was used to calculate odds ratios by
      GA using 39 weeks non-GDMA as reference. RESULTS: In all, 96,964 cases and
      176,079 controls were included. Increased risk for all adverse outcomes among
      GDMA cases was found. The nadir for intrapartum and neonatal complications was 38
      and 40 weeks, respectively, whereas for cesarean and macrosomia was 39 weeks.
      CONCLUSION: The optimal timing for IOL at term in GDMA appears to be 39 to 40
      weeks.

PMID- 26313054
TI  - Implementation of feeding guidelines in infants at risk of intestinal failure.
AB  - OBJECTIVE: To implement feeding guidelines to reduce advancement time and the
      incidence of parenteral nutrition-associated liver disease (PNALD) among
      intestinal surgical infants requiring parenteral nutrition (PN). STUDY DESIGN:
      Feeding guidelines with higher initial enteral nutrition (EN) volume and specific
      advancement criteria were implemented for surgical infants aged <6 months.
      Preimplementation and postimplementation outcomes were compared. RESULTS: There
      were 57 preimplementation and 33 postimplementation infants. The initial EN
      volume improved from 10 to 20 ml kg(-1) day(-1) (P<0.001). Time to reach 50% of
      goal calories from EN decreased by a median of 6 days (P=0.012) without a change
      in necrotizing enterocolitis incidence after resuming feeding. PNALD incidence
      decreased from 70% to 48% (P=0.046), and median peak direct bilirubin (DB)
      decreased from 5.6 to 2.3 mg dl(-1) (P=0.011). CONCLUSION: Feeding guideline
      implementation with higher initial feeding volume was well tolerated and resulted
      in faster achievement of 50% goal EN calories. PNALD incidence and peak DB were
      reduced.

PMID- 26313055
TI  - Surgical care needs of low-resource populations: an estimate of the prevalence of
      surgically treatable conditions and avoidable deaths in 48 countries.
AB  - BACKGROUND: Surgical care needs in low-resource countries are increasingly
      recognised as an important aspect of global health, yet data for the size of the
      problem are insufficient. The Surgeons OverSeas Assessment of Surgical Need
      (SOSAS) is a population-based cluster survey previously used in Nepal, Rwanda,
      and Sierra Leone. METHODS: Using previously published SOSAS data from three
      resource-poor countries (Nepal, Rwanda, and Sierra Leone), a weighted average of
      overall prevalence of surgically treatable conditions was estimated and the
      number of deaths that could have been avoided by providing access to surgical
      care was calculated for the broader community of low-resource countries. Such
      conditions included, but were not limited to, injuries (road traffic incidents,
      falls, burns, and gunshot or stab wounds), masses (solid or soft, reducible),
      deformities (congenital or acquired), abdominal distention, and obstructed
      delivery. Population and health expenditure per capita data were obtained from
      the World Bank. Low-resource countries were defined as those with a per capita
      health expenditure of US$100 or less annually. The overall prevalence estimate
      from the previously published SOSAS data was extrapolated to each low-resource
      country. Using crude death rates for each country and the calculated proportion
      of avoidable deaths, a total number of deaths possibly averted in the previous
      year with access to appropriate surgical care was calculated. FINDINGS: The
      overall prevalence of surgically treatable conditions was 11.16% (95% CI 11.15
      11.17) and 25.6% (95% CI 25.4-25.7) of deaths were potentially avoidable by
      providing access to surgical care. Using these percentages for the 48 low
      resource countries, an estimated 288.2 million people are living with a
      surgically treatable condition and 5.6 million deaths could be averted annually
      by the provision of surgical care. In the Nepal SOSAS study, the observed
      agreement between self-reported verbal responses and visual physical examination
      findings was 94.6%. Such high correlation helps to validate the SOSAS tool.
      INTERPRETATION: Hundreds of millions of people with surgically treatable
      conditions live in low-resource countries, and about 25% of the mortality
      annually could be avoided with better access to surgical care. Strengthening
      surgical care must be considered when strengthening health systems and in setting
      future sustainable development goals. FUNDING: None.

PMID- 26313056
TI  - Prevalence of chronic pain in low-income and middle-income countries: a
      systematic review and meta-analysis.
AB  - BACKGROUND: The global burden of chronic pain and disability could be related to
      unmet surgical needs. This systematic review and meta-analysis aims to
      characterise existing data regarding the prevalence and associations of chronic
      pain in low-income and middle-income countries; this is essential to allow better
      assessment of its relationship to pre-operative and post-operative pain as
      emergency and essential surgical services are expanded. METHODS: According to
      PRISMA guidelines, we searched PubMed, PsycInfo, and Cochrane registries for
      articles published before Dec 31, 2013, using the search terms "pain AND (chronic
      OR persistent) AND (low income countries OR middle income countries OR LMIC OR
      Africa OR Asia OR Central America OR South America) AND (incidence OR
      prevalence)." We excluded paediatric populations (aged younger than 18 years) and
      those with acute pain or pain associated with known trauma, surgery, infection,
      or medical disorders. FINDINGS: We identified 122 publications in 28 low-income
      and middle-income countries for systematic review; 79 surveys from general adult
      populations, elderly general populations, or workers. The prevalence of any type
      of chronic pain was 33% (95% CI 26-40) in the general adult population, 56% (36
      75) in the general elderly population, and 35% (4-88) in workers; lower back pain
      was 18% (14-24), 31% (22-41), and 44% (33-55), respectively; headache 39% (27
      53), 49% (37-60), and 52% (16-86), respectively; chronic daily headache 5% (3-7),
      not available, and 12% (8-19), respectively; musculoskeletal pain 26% (19-33),
      39% (23-57), and 86% (56-93), respectively; joint pain 14% (11-18), 42% (26-60),
      and not available, respectively; and widespread pain 14% (9-22), 22% (9-46), and
      not available, respectively. Due to limited data, meta-analysis could only be
      done in single populations for some conditions. For general adult populations,
      chronic migraine was 10% (5-20); chronic tension-type headache was 4% (2-9);
      chronic pelvic pain or prostatitis was 11% (8-17); and fibromyalgia was 4% (3-7).
      In elderly general populations, prevalence of temporomandibular disorder was 7%
      (1-31) and abdominal pain was 6% (1-28). Heterogeneity in prevalence was largely
      secondary to variable definitions of pain chronicity. Associations were not
      readily amenable to meta-analysis; yet of the 122 publications, pain was
      described in association with disability in 50, female sex in 40, older age in
      34, depression in 36, anxiety in 19, and multiple somatic complaints in 13.
      INTERPRETATION: The prevalence of pain in low-income and middle-income countries
      is consistent with Global Burden of Disease data, with higher rates in the
      elderly general population and workers than in the general adult population. 28%
      of the global burden of disease that could be averted by surgery and safe
      anaesthesia might also be related to the chronic pain burden. Trauma, cancer,
      birth complications, congenital defects, and other surgical diseases potentially
      lead to chronic pain if not treated or if treated inadequately. This meta
      analysis shows the range of chronic pain in low-income and middle-income
      countries, but has fallen short of revealing clear causes for the pain. The
      demonstration of the prevalence of chronic pain is essential as the era of global
      surgery begins, to allow benchmarking of this prevalence in the future as
      emergency and essential surgery services are expanded in low-income and middle
      income countries. FUNDING: None.

PMID- 26313057
TI  - Estimate of the global volume of surgery in 2012: an assessment supporting
      improved health outcomes.
AB  - BACKGROUND: It was previously estimated that 234.2 million operations were
      performed worldwide in 2004. The association between surgical rates and
      population health outcomes is not clear. We re-estimated global surgical volume
      to track changes over time and assess rates associated with healthy populations.
      METHODS: We gathered demographic, health, and economic data for 194 WHO member
      states. Surgical volumes were obtained from published studies and other reports
      from 2005 onwards. We estimated rates of surgery for all countries without
      available data based on health expenditure in 2012 and assessed the proportion of
      surgery comprised by caesarean delivery. The rate of surgery was plotted against
      life expectancy to describe the association between surgical care and this health
      indicator. FINDINGS: We identified 66 countries reporting surgical data between
      2005 and 2013. We estimate that 312.9 million operations (95% CI 266.2-359.5)
      took place in 2012-a 33.6% increase over 8 years; the largest proportional
      increase occurred in countries spending US$400 or less per capita on health care.
      Caesarean delivery comprised 29.8% (5.8 million operations) of the total surgical
      volume in poor health expenditure countries compared with 10.8% (7.8 million
      operations) in low health expenditure countries and 2.7% (5.1 million operations)
      in high health expenditure countries. We noted a correlation between increased
      life expectancy and increased surgical rates up to 1533 operations per 100 000
      people, with significant but less dramatic improvement above this rate.
      INTERPRETATION: Surgical volume is large and continues to grow in all economic
      environments. A single procedure-caesarean delivery-comprised almost a third of
      surgical volume in the most resource-limited settings. Surgical care is an
      essential part of health care and is associated with increased life expectancy,
      yet many low-income countries fail to achieve basic levels of service.
      Improvements in capacity and delivery of surgical services must be a major
      component of health system strengthening. FUNDING: None.

PMID- 26313058
TI  - Proposed minimum rates of surgery to support desirable health outcomes: an
      observational study based on four strategies.
AB  - BACKGROUND: The global volume of surgery in 2012 is estimated at 312.9 million
      operations per year, but rates of surgery vary substantially. Maternal health
      advocates proposed minimum caesarean delivery rates for benchmarking and to
      improve perinatal outcomes; however, this has not been done for surgery because
      the association between rates of surgical care provision as a whole and
      population health outcomes have not been well described. We use available data to
      estimate minimum rates of surgery that are associated with important health
      indicators. METHODS: We defined surgical operations as procedures done in
      operating theatres that need general or regional anaesthesia or profound sedation
      to control pain. We used four strategies to identify rates of surgery based on
      estimated rates of surgery per country for 2012 associated with life expectancy
      of 74-75 years; estimated rates of surgery associated with a maternal mortality
      ratio of less than or equal to 100 per 100 000 live births; estimated minimum
      need for surgery in the 21 Global Burden of Disease (GBD) regions based on the
      prevalence of disorders; and surgical rates from the so-called 4C countries
      (Chile, China, Costa Rica, and Cuba) identified in The Lancet Commission on
      Global Surgery as exemplary for their achievement of high health status, despite
      resource limitations. FINDINGS: Based on 2012 national surgical rates, countries
      with reported life expectancy of 74-75 years (n=17) had a median surgical rate of
      4392 (IQR 2897-4873) operations per 100 000 population annually. The median
      surgical rate associated with maternal mortality ratio lower than 100 (n=109) is
      5028 (IQR 4139-6778) operations per 100 000 population annually. The median
      surgical rate estimated for all 21 GBD regions was 4669 (IQR 4339-5291)
      operations per 100 000 population annually. The 4C countries had a mean surgical
      rate of 4344 (95% CI 2620-6068) operations per 100 000 population annually. 13 of
      the 21 GBD regions, accounting for 78% of the world's population, do not achieve
      the lowest end of the surgical rate range. INTERPRETATION: We identified a
      surprisingly 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. FUNDING: None.

PMID- 26313059
TI  - How much surgery is enough? Aligning surgical delivery with best-performing
      health systems.
AB  - BACKGROUND: Surgical delivery varies 150-fold across countries. However, no
      direct correlation exists between surgical delivery and health outcomes, making
      it difficult to pinpoint a goal for surgical scale-up. We attempted to determine
      the amount of surgery that would be delivered worldwide, if the world aligned
      itself with countries providing the best health outcomes. METHODS: The number of
      cases performed annually has previously been published for 55 countries, which we
      stratified by World Bank income group. Life expectancy, maternal mortality, under
      5 mortality, adult mortality, and a composite outcome of the four were plotted
      against reported surgical delivery. Univariate and multivariate polynomial
      regression curves were fit, and the optimum point on each regression curve was
      determined by solving for first-order conditions. The country closest to the
      optimum for each health outcome was taken as representative of the best
      performing health system. Monetary inputs to, and surgical procedures provided
      by, these health systems were scaled to the global population. FINDINGS: For the
      five health outcomes, four countries (Sweden, Germany, Singapore, and Canada)
      performed at the optimum. Currently, 318 million procedures are provided annually
      around the world. If global surgical delivery mirrored delivery in the four best
      performing countries, however, between 630 million (maternal survival) and 870
      million cases (composite outcome) would be provided annually. With population
      growth, this will increase to between 750 million and 1 billion annual cases,
      respectively, by 2030. The best-performing health systems spend roughly 10% of
      their gross domestic product on health-care, providing 9000-12 000 cases per 100
      000 individuals in the population. INTERPRETATION: To the best of our knowledge
      this is the first study to provide empirical evidence for the surgical output
      that an ideal health system would provide. The findings in this study provide a
      potential goal for surgical scale-up around the world. FUNDING: National
      Institutes of Health/National Cancer Institute.

PMID- 26313060
TI  - Projections to achieve minimum surgical rate threshold: an observational study.
AB  - BACKGROUND: Recent work has indicated an increase in surgical services,
      especially in resource poor settings. However, the rate of growth is poorly
      understood and likely insufficient to meet public health needs. We previously
      identified a range of 4344 to 5028 operations per 100 000 population annually to
      be related to desirable health outcomes. From this and other evidence, the Lancet
      Commission on Global Surgery recommends a minimum rate of 5000 operations per 100
      000 population. We evaluate rates of growth in surgery and estimate the time it
      will take to reach this minimum surgical rate threshold. METHODS: We aggregated
      2004 and 2012 country-level surgical rate estimates into the 21 Global Burden of
      Disease (GBD) regions. We calculated mean rates of surgery proportional to
      population size and estimate rate of growth between these years. We then
      extrapolated the time it will take to reach a surgical rate of 5000 operations
      per 100 000 population based on linear rates of change. FINDINGS: All but two
      regions (central Europe and southern Latin America) experienced growth in their
      surgical rates during the past 8 years; the fastest growth occurred in regions
      with the lowest surgical rates. 14 regions representing 79% of the world's
      population (5.5 billion people) did not meet the recommended surgical rate
      threshold in 2012. If surgical capacity grows at current rates, seven regions
      (central sub-Saharan Africa, east Asia, eastern sub-Saharan Africa, north Africa
      and middle east, south Asia, southeast Asia, and western sub-Saharan Africa) will
      not meet the recommended surgical rate threshold by 2035; Eastern Sub-Saharan
      Africa will not reach this level until 2124. INTERPRETATION: The rates of growth
      in surgical service delivery are exceedingly variable, but the largest growth
      rates were noted in the poorest regions. Although this study does not address the
      quality of care, and rates of surgery are unlikely to change linearly, this
      exercise is useful to project how many years it could take regions to reach
      specific surgical rates. At current rates of growth, 4.9 billion people (70% of
      the world's population) will still be living in countries below the minimum
      recommended rate of surgery in 2035. A strategy for strengthening surgical
      capacity is essential if these targets are to be met as part of integrated health
      system development. FUNDING: None.

PMID- 26313061
TI  - A qualitative study exploring contextual challenges to surgical care provision in
      21 LMICs.
AB  - BACKGROUND: Billions of people worldwide are without access to safe, affordable,
      and timely surgical care. The Lancet Commission on Global Surgery (LCoGS)
      conducted a qualitative study to understand the contextual challenges to surgical
      care provision in low-income and middle-income countries (LMICs), and how
      providers overcome them. METHODS: A semi-structured interview was administered to
      143 care providers in 21 LMICs using stratified purposive sampling to include
      both urban and rural areas and reputational case selection to identify individual
      providers. Interviews were conducted in Argentina (n=5), Botswana (3), Brazil
      (10), Cape Verde (4), China (14), Colombia (4), Ecuador (6), Ethiopia (10), India
      (15), Indonesia (1), Mexico (9), Mongolia (4), Namibia (2), Pakistan (13), Peru
      (5), Philippines (1), Sierra Leone (11), Tanzania (5), Thailand (2), Uganda (9),
      and Zimbabwe (15). Local collaborators of LCoGS conducted interviews using a
      standardised implementation manual and interview guide. Questions revolved around
      challenges or barriers in the area of access to care for patients; challenges or
      barriers in the area of in-hospital care for patients; and challenges or barriers
      in the area of governance or health policy. De-identified interviews were coded
      and interpreted by an independent analyst. FINDINGS: Providers across continent
      and context noted significant geographical, financial, and educational barriers
      to access. Surgical care provision in the rural hospital setting was hindered by
      a paucity of trained workforce, and inadequacies in basic infrastructure,
      equipment, supplies, and access to banked blood. In urban areas, providers face
      high patient volumes combined with staff shortages, minimal administrative
      support, and poor interhospital care coordination. At a policy level, providers
      identified regulations that were inconsistent with the realities of low-resource
      care provision (eg, a requirement to provide 'free' care to certain populations
      but without any guarantee for funding). Regional variation did exist on some
      matters, particularly related to prevalence of patient-provider mistrust and
      supply chain failures. Everywhere, providers have created innovative workarounds
      to overcome some of these barriers, such as clever financing mechanisms for
      planned surgery (eg, raising donated farm animals for cash in Zimbabwe, Ethiopia,
      and India), provision in scheduling and accommodations to facilitate patients
      from afar, reduction of cost and waste through re-sterilisation of disposable
      supplies, and locally sourcing consumables (eg, hand cleaning solution made of
      alcohol from the local distillery in India). INTERPRETATION: Although some
      variation exists between countries, the challenges to surgical care provision are
      largely consistent and based on local resource availability; underfunded rural
      hospitals faced similar challenges worldwide. Global efforts to scale-up surgical
      services can focus on these commonalities (eg, investments in infrastructure,
      workforce), while local governments can tailor solutions to key contextual
      differences (eg, community-based outreach, supply chains, professional
      management, and interhospital coordination). FUNDING: None.

PMID- 26313062
TI  - Geospatial mapping to estimate timely access to surgical care in nine low-income
      and middle-income countries.
AB  - BACKGROUND: The Lancet Commission on Global Surgery calls for universal access to
      safe, affordable, and timely surgical care. Two requisite components of timely
      access are (1) the ability to reach a surgical provider in a given timeframe, and
      (2) the ability to receive appropriately prompt care from that provider. We chose
      a threshold of 2 h in view of its relevance in time-to-death in post-partum
      haemorrhage. Here, we use geospatial mapping to enumerate the percentage of a
      nation's population living within 2 h of a surgeon and the surgeon-to-population
      ratio for each provider. METHODS: Geospatial mapping was used to identify the
      population living within a 2-h driving distance (access zone) of a health-care
      facility staffed by a surgeon. Surgeon locations were extracted from Ministries
      of Health, professional society databases, and published literature for countries
      which had available data. Data were reviewed by individuals knowledgeable of in
      country distribution. Spatial distribution of providers was mapped with Google
      Maps engine. Access zones were constructed around every provider through
      estimation of driving times in Google Maps. The number of people living within
      zones was estimated with the Socioeconomic Data and Applications Center
      Population Estimation Service. Surgeon-to-population ratios were constructed for
      every individual access zone and averaged to report a single ratio. FINDINGS:
      Results (% country's population living within an access zone; average
      surgeon:population ratio within all access zones) are reported for nine countries
      with available data: Somaliland (16.9%; 1:118 306), Botswana (31.0%; 1:64 635),
      Ethiopia (39.6%; 1:229 696), Rwanda (41.3%; 1:158 484), Namibia (43.4%; 1:69
      385), Zimbabwe (54%; 1:148 292), Mongolia (55.5%; 1:10 500), Sierra Leone (70.3%;
      1:106 742), and Pakistan (84.4%, 1:139 299). Surgeon-to-population ratios vary
      substantially even within countries; in Sierra Leone, urban access zones have a
      ratio of 1:45 058 and rural access zones have a ratio of 1:467 929.
      INTERPRETATION: Surgical access is poor in many low-income and middle-income
      countries, even when using a narrow definition of surgical access consisting only
      of timeliness. Living outside of an access zone makes timely access to surgical
      care highly unlikely, and in view of low surgeon-to-population ratios and poor
      prehospital transport, even living within a 2-h access zone might not confer 2-h
      access. Investments in infrastructure and training must be prioritised to address
      widespread disparity in access to timely surgery. FUNDING: None.

PMID- 26313063
TI  - Trauma and orthopaedic capacity of 267 hospitals in east central and southern
      Africa.
AB  - BACKGROUND: Trauma and road traffic accidents are predicted to increase
      significantly in the next decade in low-income and middle-income countries. The
      College of Surgeons of East, Central, and Southern Africa (COSECSA) covers
      Ethiopia, Kenya, Tanzania, Uganda, Rwanda, Burundi, Mozambique, Malawi, Zimbabwe,
      and Zambia. Ministry of Health websites for these ten countries show that 992
      hospitals are covering an estimated 318 million people. METHODS: The WHO Tool for
      Situational Analysis to Assess Emergency and Essential Surgical Care was used
      with added questions relevant to trauma and orthopaedic care. A web-based survey
      platform was used and hospitals were contacted via COSECSA representatives.
      Consent to share data was requested, anonymised for country and hospital.
      FINDINGS: 267 (27%) of 992 hospitals completed the survey. 185 were district
      level hospitals and 82 were referral or tertiary level hospitals. Formal accident
      and emergency departments were present in only 29% of district hospitals (95% CI
      22.5-35.5) and 35% (24.7-45.3) of referral or tertiary level hospitals. The mean
      number (SD) of surgeons was 1.4 (3.0) in district hospitals and 2.6 (4.6) in
      referral or tertiary level hospitals. The mean number (SD) of orthopaedic
      surgeons was 0.3 (0.9) in district hospitals and 0.5 (0.9) in referral or
      tertiary level hospitals. Medically qualified anaesthetists were available in 16%
      (95% CI 10.7-21.3) of district hospitals and 20% (11.4-28.6) of referral or
      tertiary level hospitals. C arm radiography was available in 3% (95% CI 0.5-5.5)
      of district hospitals and 32% (21.9-42.1) of referral or tertiary level
      hospitals. CT scanning was available in 6% (95% CI 2.6- 9.4) of district
      hospitals and 21% (12.2-29.8) of referral or tertiary level hospitals. Closed
      fracture treatment was offered in 75% (95% CI 68.8- 81.2) of district hospitals
      and 82% (73.7-90.3) of referral or tertiary level hospitals. 37% (95% CI 30.1
      43.9) of district hospitals and 40% (29.4-50.6) of referral or tertiary level
      hospitals had adequate instruments for the surgical treatment of fractures, but
      only 7% (3.4-10.6) of district hospitals and 8% (2.1-13.9) of referral or
      tertiary level hospitals had a sustainable supply of fracture implants. Elective
      orthopaedic surgery took place in 30% (95% 23.4- 36.6) of district hospitals and
      34% (23.8-44.2) of referral or tertiary level hospitals. Ponseti treatment of
      clubfoot was available at 46% (95% 38.8-53.2) of district hospitals and 44% (33.3
      54.7) of referral or tertiary level hospitals. INTERPRETATION: This study has
      limitations in that only 27% of eligible hospitals completed the survey, and it
      is certainly possible that there could be bias in that the less well resourced
      institutions could also be less likely to cooperate with data collection. Thus,
      it is possible that the figures we present overestimate the resources available
      in the region as a whole. However, despite the limitations in data quality, it is
      clear that current capacity to treat trauma and orthopaedic conditions is very
      limited, with particular areas of concern being manpower, training, facilities,
      and equipment. COSECSA will use these data as a baseline for further surveys and
      to develop a strategy to improve trauma and orthopaedic care in the region.
      FUNDING: UK Department for International Development (DFID).

PMID- 26313064
TI  - Surgery in district hospitals in rural Uganda-indications, interventions, and
      outcomes.
AB  - BACKGROUND: There is a vast unmet need for surgical interventions in resource
      scarce settings. The poorest 2 billion people share 3.5% of the world's
      operations. The highest burden of surgical disease is seen in Africa where
      surgery could avert many deaths. Prospective studies investigating interventions,
      indications, and outcomes including perioperative mortality rates (POMR) after
      surgery are scant. The aim of the study was to describe the situation of surgery
      in a low-income setting in sub-Saharan Africa. METHODS: In this descriptive,
      facility-based study, data were prospectively collected in questionnaires by 41
      staff employed at two hospitals (Iganga General Hospital and Buluba Mission
      Hospital) in eastern Uganda during 4 months (major surgeries) and 3 months (minor
      surgeries) in 2011. Data included patient characteristics, interventions,
      indications for surgery, and in-hospital mortality after surgery. Descriptive
      statistical methods were used to analyse the data. FINDINGS: 2701 patients
      underwent 2790 surgical interventions. Of these, 1051 patients underwent major
      surgery, which corresponds to a major surgery rate of 224.8 per 100 000
      population. Most patients undergoing major surgery were women (n=923, 88%).
      Pregnancy related complications (n=747, 66%) leading to caesarean section (n=496,
      47%) and evacuation (n=244, 22%) or gynaecological conditions (n=114, 10%) were
      common indications for surgery. General surgery interventions registered were
      herniorrhaphy (n=103, 9%), explorative laparotomy (n=60, 5%), and appendicectomy
      (n=31, 3%). Overall, the POMR was 0.6% (16 deaths); for major surgery it was 1.3%
      (14 deaths) and for minor surgeries it was 0.1% (two of 1650 patients). High POMR
      were seen following explorative laparotomy (13.3%, eight deaths) and caesarean
      section (0.8%, four deaths). Of the 510 babies delivered through caesarean
      section, 59 (12%) were still born or died before discharge. INTERPRETATION: Rates
      of surgery are low in the study setting compared with in high-income settings
      where surgical rates exceed 11 000 per 100 000 population. POMR are high after
      exploratory laparotomy and caesarean section. Although very detailed, a larger
      study could be undertaken to investigate the situation in other settings.
      Underlying reasons leading to death and quality of surgical care should be
      investigated further so that POMR can be reduced in this setting. FUNDING: The
      Swedish Society of Medicine and the Golje Foundation.

PMID- 26313065
TI  - Rates of caesarean section and total volume of surgery in Sierra Leone: a
      retrospective survey.
AB  - BACKGROUND: Surgical services are essential components of health-care systems.
      Monitoring of surgical activity is important, but resource demanding. Simpler
      tools to estimate surgical volume, particularly in low-income countries, are
      needed. Previous work hypothesises that the relative frequency of caesarean
      sections, expressed as a proportion of total operative procedures, could serve as
      a proxy measure of surgical capacity. We aimed to establish nationwide and
      district-wide rates of surgery and caesarean sections, and to explore
      correlations between districts rates for caesarean sections and corresponding
      rates for total volume of surgery in Sierra Leone in 2012. METHODS: A nationwide,
      exhaustive, retrospective, facility-based study of all surgical providers and
      surgical procedures was performed in Sierra Leone. Between Jan 14, and May 20,
      2013, four teams of 12 medical students collected data on the characteristics of
      the institutions and of the surgeries performed in 2012. Data were retrieved from
      operation, anaesthesia, and delivery logbooks. FINDINGS: Of 60 facilities
      performing surgery, complete annual data for 2012 was collected from 58 (97%)
      institutions. 24 152 surgical procedures identified, gave a national rate of 400
      surgeries per 100 000 inhabitants (district range 32-909 per 100 000 [IQR 95-502
      per 100 000]). National caesarean section rate was 2.1% (district range 0.3-4.0%
      [IQR 0.8-2.1]). District caesarean sections rate significantly correlated with
      the rate of total surgical procedures per 100 000 population (p<0.01). With known
      caesarean section rate, total volume of surgeries per 100 000 can be calculated
      with the equation: -9.8 + 4.68 * caesarean sections per 100 000. INTERPRETATION:
      The close correlation between rate of caesarean section and population rates of
      total volume of surgery at district level in Sierra Leone indicates that rate of
      caesarean section should be further explored as a proxy indicator for overall
      surgical volume in low performing settings. By collecting data from three
      sources, missing procedures was considered less likely. FUNDING: Norwegian
      University of Science and Technology.

PMID- 26313066
TI  - Injury assessment in three low-resource settings: a reference for worldwide
      estimates.
AB  - BACKGROUND: Trauma has become a worldwide pandemic. Without dedicated public
      health interventions, fatal injuries will rise 40% and become the 4th leading
      cause of death by 2030, with the burden highest in low-income and middle-income
      countries (LMICs). The aim of this study was to estimate the prevalence of
      traumatic injuries and injury-related deaths in low-resource countries worldwide,
      using population-based data from the Surgeons OverSeas Assessment of Surgical
      Need (SOSAS), a validated survey tool. METHODS: Using data from three resource
      poor countries (Nepal, Rwanda, and Sierra Leone), a weighted average of injury
      prevalence and deaths due to injury was calculated and extrapolated to low
      resource countries worldwide. Injuries were defined as wounds from road traffic
      injuries (bus, car, truck, pedestrian, and bicycle), gunshot or stab or slash
      wounds, falls, work or home incidents, and burns. The Nepal study included a
      visual physical examination that confirmed the validity of the self-reported
      data. Population and annual health expenditure per capita data were obtained from
      the World Bank. Low-resource countries were defined as those with an annual per
      capita health expenditure of US$100 or less. FINDINGS: The overall prevalence of
      lifetime injury for these three countries was 18.03% (95% CI 18.02-18.04); 11.64%
      (95% CI 11.53-11.75) of deaths annually were due to injury. An estimated
      prevalence of lifetime injuries for the total population in 48 low-resource
      countries is 465.7 million people; about 2.6 million fatal injuries occur in
      these countries annually. INTERPRETATION: The limitations of this observational
      study with self-reported data include possible recall and desirability bias.
      About 466 million people at a community level (18%) sustain at least one injury
      during their lifetime and 2.6 million people die annually from trauma in the
      world's poorest countries. Trauma care capacity should be considered a global
      health priority; the importance of integrating a coordinated trauma system into
      any health system should not be underestimated. FUNDING: None.

PMID- 26313067
TI  - The struggle for equity: an examination of surgical services at two NGO hospitals
      in rural Haiti.
AB  - BACKGROUND: Health systems must deliver care equitably to serve the poor. Both
      L'Hopital Albert Schweitzer (HAS) and L'Hopital Bon Sauveur (HBS) have
      longstanding commitments to provide equitable surgical care in rural Haiti. HAS
      charges fees that reflect a preference for the rural population near the
      hospital, with free care available for the poorest. HBS does not charge fees. The
      two hospitals are otherwise similar in surgical capacity and rural location.
      Using geography as a proxy for poverty, we analysed the equity achieved under the
      financial system at both hospitals. METHODS: We retrospectively reviewed
      operative case-logs for general surgery and orthopaedic cases at both hospitals
      from June 1, to Aug 31, 2012. The records were compared by total number of
      operations, geographic distribution of patients, and number of elective
      operations. The service areas were defined as the governmental administrative
      units closest to both hospitals. For HAS, we analysed the number of operations
      performed on patients from the most poor and least poor regions within the
      service area; similarly detailed geographic information was not available from
      HBS. Rates were compared with chi(2) tests. The Ethics Committees at both
      hospitals and the Institutional Review Board at Partners Healthcare approved the
      study. FINDINGS: Patients from the rural service area received 306 operations
      (86.2%) at HAS compared with 149 (38.1%) at HBS (p<0.0001). Only 16 operations
      (4.5%) at HAS were performed on patients from outside the service area for
      elective conditions compared with 179 (47.0%) at HBS (p<0.0001). Within its rural
      service area, HAS performed fewer operations on patients from the most destitute
      areas compared with other locations (4.0 operations per 10 000 population vs 10.1
      operations per 10 000 population; p<0.0001). INTERPRETATION: Use of fees as part
      of an equity strategy will likely disadvantage the poorest patients, while
      providing care without fees might encourage patients to travel from urban areas
      that contain other hospitals. Health systems striving to serve the poor should
      continually evaluate and seek to improve equity, even within systems that provide
      free care. FUNDING: None.

PMID- 26313068
TI  - Assessment of caesarean section and inguinal hernia repair as proxy indicators of
      total number of surgeries.
AB  - BACKGROUND: The traditional instruments used to assess surgical capacity in low
      income countries require substantial amounts of time and resources, and have thus
      not been systematically used in this context. Proxy indicators have been
      suggested as a simpler method to estimate surgical volume. The aim of this study
      was to assess caesarean section and inguinal hernia repair as proxy indicators of
      the total number of surgeries performed per capita in a given region in Sierra
      Leone in sub-Saharan Africa. METHODS: Avaliable handwritten surgical data were
      compiled from 58 (96.7%) health institutions that performed WHO defined major
      surgery in Sierra Leone in 2012 (from Jan 1, to Dec 31). 24 152 surgical
      procedures were included in the study. Validity of proxy indicators was tested by
      logistic regression analyses with the rate of caesarean sections compared with
      total operations (% CS), hernia repairs (% HR), or both (% CS plus HR) as
      dependent variables and the operations per 100 000 capita as the covariate.
      FINDINGS: The number of operations per 100 000 capita for the 13 districts of
      Sierra Leone varied from 909 in the urban Western District to 32 in the rural
      district of Moyamba. There was a significant negative correlation between each of
      the proxy indicators and the number of operations per 100 000 capita. For changes
      in the operations per 100 000 capita of 100, we obtained an estimated odds ratio
      for the % CS proxy indicator of 0.675 (95% CI 0.520-0.876; p<0.01), % HR being
      0.822 (0.688-0.983; p<0.05), and for % CS plus HR being 0.838 (0.731-0.962;
      p<0.05). INTERPRETATION: The unmet need for surgical services in Sierra Leone can
      be estimated by either of the three proxy indicators. However, it seems that % CS
      is more sensitive to small changes in operations per 100 000 capita compared with
      the % HR. There is no obvious added benefit of use of the combined proxy
      indicator. Although this study shows that proxy indicators are a promising method
      to evaluate surgical activity, this is a cross-sectional study and can thus only
      show correlation. Longitudinal studies would strengthen these findings. FUNDING:
      Faculty of Medicine, Norwegian University of Science and Technology, Trondheim,
      Norway, and CapaCare.

PMID- 26313069
TI  - A time-driven activity-based costing model to improve health-care resource use in
      Mirebalais, Haiti.
AB  - BACKGROUND: In resource-limited settings, efficiency is crucial to maximise
      resources available for patient care. Time driven activity-based costing (TDABC)
      estimates costs directly from clinical and administrative processes used in
      patient care, thereby providing valuable information for process improvements.
      TDABC is more accurate and simpler than traditional activity-based costing
      because it assigns resource costs to patients based on the amount of time
      clinical and staff resources are used in patient encounters. Other costing
      approaches use somewhat arbitrary allocations that provide little transparency
      into the actual clinical processes used to treat medical conditions. TDABC has
      been successfully applied in European and US health-care settings to facilitate
      process improvements and new reimbursement approaches, but it has not been used
      in resource-limited settings. We aimed to optimise TDABC for use in a resource
      limited setting to provide accurate procedure and service costs, reliably predict
      financing needs, inform quality improvement initiatives, and maximise efficiency.
      METHODS: A multidisciplinary team used TDABC to map clinical processes for
      obstetric care (vaginal and caesarean deliveries, from triage to post-partum
      discharge) and breast cancer care (diagnosis, chemotherapy, surgery, and support
      services, such as pharmacy, radiology, laboratory, and counselling) at Hopital
      Universitaire de Mirebalais (HUM) in Haiti. The team estimated the direct costs
      of personnel, equipment, and facilities used in patient care based on the amount
      of time each of these resources was used. We calculated inpatient personnel costs
      by allocating provider costs per staffed bed, and assigned indirect costs
      (administration, facility maintenance and operations, education, procurement and
      warehouse, bloodbank, and morgue) to various subgroups of the patient population.
      This study was approved by the Partners in Health/Zanmi Lasante Research
      Committee. FINDINGS: The direct cost of an uncomplicated vaginal delivery at HUM
      was US$62 and the direct cost of a caesarean delivery was US$249. The direct
      costs of breast cancer care (including diagnostics, chemotherapy, and mastectomy)
      totalled US$1393. A mastectomy, including post-anaesthesia recovery and inpatient
      stay, totalled US$282 in direct costs. Indirect costs comprised 26-38% of total
      costs, and salaries were the largest percentage of total costs (51-72%).
      INTERPRETATION: Accurate costing of health services is vital for financial
      officers and funders. TDABC showed opportunities at HUM to optimise use of
      resources and reduce costs-for instance, by streamlining sterilisation procedures
      and redistributing certain tasks to improve teamwork. TDABC has also improved
      budget forecasting and informed financing decisions. HUM leadership recognised
      its value to improve health-care delivery and expand access in low-resource
      settings. FUNDING: Boston Children's Hospital, Harvard Business School, and
      Partners in Health.

PMID- 26313070
TI  - Major surgery in south India: a retrospective audit of hospital claim data from a
      large community health insurance programme.
AB  - BACKGROUND: Information about use of major surgery in India is scarce. This study
      aims to bridge this gap by auditing hospital claims from the Rajiv Aarogyasri
      Community Health Insurance Scheme (RACHIS) that provides access to free tertiary
      care for major surgery through state-funded insurance to 68 million beneficiaries
      with limited household incomes-81% of population in states of Telangana and
      Andhra Pradesh (combined Human Development Index 0.485). Beneficiary households
      receive an annual coverage of INR 200 000 (US$3333) for admissions to any
      empanelled public or private hospital. METHODS: Publicly available deidentified
      hospital claim data for all surgical procedures conducted between mid-2008 and
      mid-2012 were compiled across all 23 districts in Telangana and Andhra Pradesh.
      FINDINGS: 677 332 surgical admissions (80% at private hospitals) were recorded at
      a mean annual rate of 259 per 100 000 beneficiaries (95% CI 235-283), excluding
      cataract and caesarean sections as these were not covered under the insurance
      programme. Men accounted for 56% of admissions. Injury was the most common cause
      for surgical admission (185 733; 27%) with surgical correction of long bone
      fractures being the most common procedure (144 997; 20%) identified in the audit.
      Diseases of digestive (110 922; 16%), genitourinary (82 505; 12%), and
      musculoskeletal system (70 053; 10%) were other leading causes for surgical
      admissions. Most hospital bed-days were used for injuries (584 days per 100 000
      person years; 31%), digestive diseases (314 days; 17%), and musculoskeletal
      system (207 days; 11%), costing 19% (INR 4.4 billion), 13% (3.03 billion), and
      11% (2.5 billion) of claims, respectively. Cardiovascular surgeries (53 023; 8%)
      alone accounted for 21% (INR 4.9 billion) of cost. Annual per capita cost of
      surgical claims was US$1.49 (95% CI 1.32-1.65). INTERPRETATION: Our findings are
      limited to a population socioeconomically representative of India and other
      countries with low-income and middle-income. Despite near universal access for
      major surgery, use continues to remain low, at levels expected in countries with
      per capita health expenditure below US$100, and lower than a tenth of rates
      estimated at spending (US$400-1000) comparable with financial access provided.
      Hence, strategies beyond traditional financing for care are required to improve
      use of surgery in LMICs. FUNDING: The George Institute for Global Health.

PMID- 26313071
TI  - Waiting at the hospital door: a prospective, multicentre assessment of third
      delay in four tertiary hospitals in India.
AB  - BACKGROUND: A common framework to assess delays in health-care in countries with
      low-income and middle-income (LMICs) defines three time periods that add to the
      interval between onset of symptoms and treatment; the time it takes to receive
      care after hospital arrival is known as the third delay. Tertiary centres in
      LMICs are known to be overcrowded and under-capacity, but few studies have
      formally assessed the third delay. This study aims to quantify the third delay in
      LMIC tertiary centres and identify contributing factors at the facility level.
      METHODS: A prospective multicentre study was conducted from July, 2013, to July,
      2014, in four tertiary care hospitals in the three largest cities in India:
      Mumbai, Delhi, and Kolkata. The time from patient arrival to the time when vital
      signs were first recorded was used as a proxy for the third delay. This delay was
      recorded by the research officers for those patients who were directly observed.
      For the rest of the patients the data were collected from patient records.
      Qualitative interviews were conducted with a subset of patients exploring reasons
      for the delay. FINDINGS: Data were collected for 5087 patients (1664 from Delhi,
      469 from Mumbai centre-1, 711 from Mumbai centre-2, and 2243 from Kolkatta);
      median age was 30 years (IQR 20-45), 3944 (78%) were men, 3372 (66%) were
      transfers from other facilities, and 3424 (67.3%) arrived in an ambulance.
      Researchers directly observed 1392 (27.4%) patients from arrival to time of vital
      signs. There were wide variations in delays between groups, transferred versus
      direct presentation (0 min vs 20 min) and in between hospitals (median time 0.0
      min in Mumbai to 1.5 h in Kolkatta) and in groups within each hospital. The
      reasons for delay were multifactorial: administrative (police case recordings,
      admission paper registration), logistical (no vacant beds, no physician
      available), and process-based (investigations before vitals, multiple patients at
      one time, junior physicians in-charge); process based reasons were the most
      common (80%). INTERPRETATION: Delays in care persist in tertiary centres in LMICs
      for a variety of reasons. Low-cost but context-specific changes that optimise
      care processes like prioritisation and transfer protocols could yield major
      reductions in third delay. Adoption of best practices of the better performing
      hospitals in the Indian setting will help to improve the trauma quality practices
      in India. FUNDING: The Laerdal Foundation for Acute Medicine and the Swedish
      National Board of Health and Welfare.

PMID- 26313072
TI  - The role of facility-based surgical services in addressing the national burden of
      disease in New Zealand: an index of surgical incidence based on country-specific
      disease prevalence.
AB  - BACKGROUND: Surgery is a crucial component of health systems, yet its actual
      contribution has been difficult to define. We aimed to link use of national
      hospital service with national epidemiological surveillance data to describe the
      use of surgical procedures in the management of a broad spectrum of conditions.
      METHODS: We compiled Australian Modification-International Classification of
      Diseases-10 codes from the New Zealand National Minimum Dataset, 2008-11. Using
      primary cause of admission, we aggregated admissions to 91 hospitals into 119
      disease states and 22 disease subcategories of the WHO Global Health Estimate
      (GHE). We queried each admission for any surgical procedure in a binary manner to
      determine the frequency of admitted patients whose care required surgery.
      Surgical procedures were defined as requiring general or neuroaxial anaesthesia.
      We then divided the volume of surgical cases by counts of disease prevalence from
      the GBD 2010 to determine surgical incidence. This study was approved by the
      University of Otago Human Ethics Committee (Health; Reference Number HD14/42).
      Raw data was only handled by coauthors with direct affiliation with the New
      Zealand Ministry of Health. FINDINGS: Between 2008 and 2011, there were 1 108 653
      hospital admissions with 275 570 associated surgical procedures per year.
      Surgical procedures were associated with admissions for all 22 GHE disease
      subcategories and 116 of 119 GHE disease states (excluding intestinal nematode
      infections, iodine deficiency, and vitamin A deficiency). The subcategories with
      the largest surgical case volumes were unintentional injuries (48 073),
      musculoskeletal diseases (38 030), and digestive diseases (27 640), and the
      subcategories with the smallest surgical case volumes were nutritional
      deficiencies (13), neonatal conditions (204), and infectious and parasitic
      diseases (982). Surgical incidence ranged widely by individual disease states
      with the highest in other neurological conditions, abortion, appendicitis,
      obstructed labour, and maternal sepsis. INTERPRETATION: This study confirms
      previous research that surgical care is required across the entire spectrum of
      GHE disease subcategories, showing the crucial role of operative intervention in
      health systems. Surgical incidence might be useful as an index to estimate the
      need for surgical procedures in other populations. FUNDING: None.

PMID- 26313073
TI  - Establishment of a urology service in a developing country: an observational
      study of outcomes in transurethral prostate resection procedures in Vanuatu.
AB  - BACKGROUND: The Royal Australasian College of Surgeons (RACS) via the Pacific
      Island Program (PIP) administer yearly urology visits to Vanuatu to perform
      surgery and deliver training in the management of urological conditions. In
      conjunction with the Vanuatu Ministry of Health a self-sufficient urology service
      has developed, specifically performing transurethral resection of the prostate
      (TURP) procedures. We review the TURP outcomes for the PIP and detail the
      development and outcomes of the first independent TURP service in the Pacific.
      METHODS: With retrospective local and RACS medical records, an observational
      study was performed of TURP procedures undertaken in Port Vila Central Hospital,
      Vanuatu over 6 years. Outcome measures comprised significant morbidity, prolonged
      post-operative admission, blood transfusion, TUR syndrome, successful trial of
      void, postoperative urinary incontinence, and perioperative mortality.
      Comparisons were made with univariate analysis between the RACS, local team, and
      international standardised values, with t-tests for continuous variables, and
      with Fisher's exact test for binary variables. FINDINGS: Since 2009, a total of
      117 TURP procedures were performed. 84 by the PIP team and following training
      both in Vanuatu and Australia; the local team independently performed 33 TURPs.
      Comparisons of all outcomes measured between the local and PIP teams showed no
      statistically significant differences (appendix). 29 patients overall (22 in the
      PIP group and seven in the local group) required blood transfusions, eight (seven
      and one) failed their trial of void, 10 (seven and three) had a prolonged post
      operative admission (>7 days); two patients died in the post-operative period
      both in the PIP group). 10 (seven and three) had postoperative urinary
      incontinence. There was no difference between mean length of stay (4.07 days vs
      4.7 days; p=0.2081) and haemaglobin loss with no cases of TUR syndrome. Only the
      rate of transfusion was statistically significantly higher in the Vanuatu cohorts
      when compared with international standards (appendix). INTERPRETATION: The
      development of a local urological service and in particular a TURP service is a
      first for a Pacific Island Nation. Baseline data were obtained with encouraging
      outcomes reflecting careful patient selection, cautious management, and expertise
      accumulation. Planned prospective audit should overcome some of the difficulties
      encountered in performing a longitudinal study in a developing nation with
      suboptimum follow-up and challenging medical records. Through linkage between the
      PIP and the Vanuatu Ministry of Health capacity building an independent service
      provision can be achieved. This model could be replicated to establish a
      sustainable and self-sufficient surgical service in a developing country.
      FUNDING: None.

PMID- 26313074
TI  - Monitoring and evaluating surgical care: defining perioperative mortality rate
      and standardising data collection.
AB  - BACKGROUND: Case volume per 100 000 population and perioperative mortality rate
      (POMR) are key indicators to monitor and strengthen surgical services. However,
      comparisons of POMR have been restricted by absence of standardised approaches to
      when it is measured, the ideal denominator, need for risk adjustment, and whether
      data are available. We aimed to address these issues and recommend a minimum
      dataset by analysing four large mixed surgical datasets, two from well-resourced
      settings with sophisticated electronic patient information systems and two from
      resource-limited settings where clinicians maintain locally developed databases.
      METHODS: We obtained data from the New Zealand (NZ) National Minimum Dataset, the
      Geelong Hospital patient management system in Australia, and purpose-built
      surgical databases in Pietermaritzburg, South Africa (PMZ) and Port Moresby,
      Papua New Guinea (PNG). Information was sought on inclusion and exclusion
      criteria, coding criteria, and completeness of patient identifiers, admission,
      procedure, discharge and death dates, operation details, urgency of admission,
      and American Society of Anesthesiologists (ASA) score. Date-related errors were
      defined as missing dates and impossible discrepancies. For every site, we then
      calculated the POMR, the effect of admission episodes or procedures as
      denominator, and the difference between in-hospital POMR and 30-day POMR. To
      determine the need for risk adjustment, we used univariate and multivariate
      logistic regression to assess the effect on relative POMR for each site of age,
      admission urgency, ASA score, and procedure type. FINDINGS: 1 365 773 patient
      admissions involving 1 514 242 procedures were included, among which 8655 deaths
      were recorded within 30 days. Database inclusion and exclusion criteria differed
      substantially. NZ and Geelong records had less than 0.1% date-related errors and
      greater than 99.9% completeness. PMZ databases had 99.9% or greater completeness
      of all data except date-related items (94.0%). PNG had 99.9% or greater
      completeness for date of birth or age and admission date and operative procedure,
      but 80-83% completeness of patient identifiers and date related items. Coding of
      procedures was not standardised, and only NZ recorded ASA status and complete
      post-discharge mortality. In-hospital POMR range was 0.38% in NZ to 3.44% in PMZ,
      and in NZ it underestimated 30-day POMR by roughly a third. The difference in
      POMR by procedures instead of admission episodes as denominator ranged from 10%
      to 70%. 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. INTERPRETATION: Hospitals can
      collect and provide data for case volume and POMR without sophisticated
      electronic information systems. POMR should initially be defined by in-hospital
      mortality because post-discharge deaths are not usually recorded, and with
      procedures as denominator because details allowing linkage of several operations
      within one patient's admission are not always present. Although age and admission
      urgency are independently associated with POMR, and ASA and case mix were not
      included, risk adjustment might not be essential because the relative odds
      between sites persisted. Standardisation of inclusion criteria and definitions is
      needed, as is attention to accuracy and completeness of dates of procedures,
      discharge and death. A one-page, paper-based form, or alternatively a simple
      electronic data collection form, containing a minimum dataset commenced in the
      operating theatre could facilitate this process. FUNDING: None.

PMID- 26313075
TI  - The global blood supply: a literature review.
AB  - BACKGROUND: A safe and sufficient blood supply is requisite for a functional
      surgical system. Although the disparity in blood donation rates between low
      income and middle-income countries (LMICs) and high-income countries is well
      documented, less is known about the reasons for this inequity, which compromises
      efforts to remedy it. We aimed to review the state of the blood supply and
      elucidate unique country-specific challenges in each of the world's 196
      countries. METHODS: We searched PubMed, MEDLINE, Google Scholar, and WHO reports
      using the search terms "blood donor", "blood donation","blood safety", "blood
      bank", "transfusion safety", and "blood services". After an initial review of
      existing literature, we did a comprehensive country-by-country search of the
      aforementioned electronic databases, WHO regional reports, Ministry of Health
      websites, and National Blood Transfusion Services data for specific indicators
      and data points used to compare blood supply and safety across countries. These
      included donation rate per 1000 population, percent of donations from voluntary
      non-remunerated donors, number of blood banks or centres, and national blood
      policies. Both quantitative and descriptive data are included in a summary table
      in the appendix of the Lancet Commission on Global Surgery. FINDINGS: Our review
      yielded 117 publications with data for 188 countries: 101 peer-reviewed
      manuscripts with 13 reporting data for high-income countries and 88 for LMICs, 16
      WHO publications, and a subsequent search of select websites to collect
      additional country-specific indicator data. Generally, blood donation is limited
      because of poor health infrastructure (28 LMIC and four high-income country
      manuscripts), low public awareness of donation practices and safety (22 LMIC
      manuscripts), and stigmas surrounding voluntary blood donations, especially in
      LMICs. Most blood banks and donation centres are located in urban centres,
      inaccessible to those in rural areas. The prevalence of transfusion-transmissible
      infections in the blood supply is higher in LMICs (30 LMIC manuscripts),
      resulting in high discard rates and increased transfusion risks. Two-thirds of
      countries have a national blood policy in place, but are often unable to
      efficiently coordinate and regulate blood services nationwide. To overcome these
      barriers, some countries have developed innovative solutions. INTERPRETATION: The
      blood supply in LMICs is of insufficient quantity and safety, and the reasons for
      these deficits are multifactorial. Addressing blood supply inadequacies requires
      focused attention at both local and global levels. Political prioritisation and
      innovative solutions to the blood crisis will be necessary to improve this
      situation and will require a culturally cognizant, pro-poor, pro-equity approach.
      Reviewing successful approaches to this crisis employed by some countries can be
      helpful in charting a way forward. FUNDING: None.

PMID- 26313076
TI  - Use and definitions of perioperative mortality rates in low-income and middle
      income countries: a systematic review.
AB  - BACKGROUND: Aggregate and risk-stratified perioperative mortality rates (POMR)
      are well-documented in high-income countries where surgical databases are common.
      In many low-income and middle-income country (LMIC) settings, such data are
      unavailable, compromising efforts to understand and improve surgical outcomes. We
      undertook a systematic review to determine how POMR is used and defined in LMICs
      and to inform baseline rates. METHODS: We searched PubMed for all articles
      published between Jan 1, 2009, and Sept 1, 2014, reporting surgical mortality in
      LMICs. Search criteria, inclusion and exclusion criteria, and study assessment
      methodology are reported in the appendix. Titles and abstracts were screened
      independently by two reviewers. Full-text review and data extraction were
      completed by four trained clinician coders with regular validation for
      consistency. We extracted the definition of POMR used, clinical risk scores
      reported, and strategies for risk adjustment in addition to reported mortality
      rates. FINDINGS: We screened 2657 abstracts and included 373 full-text articles.
      493 409 patients in 68 countries and 12 surgical specialties were represented.
      The most common definition for the numerator of POMR was in-hospital deaths
      following surgery (55.3%) and for the denominator it was the number of operative
      patients (96.2%). Few studies reported preoperative comorbidities (41.8%), ASA
      status (11.3%), and HIV status (7.8%), with a smaller proportion stratifying on
      or adjusting mortality for these factors. Studies reporting on planned procedures
      recorded a median mortality of 1.2% (n=121 [IQR 0.0-4.7]). Median mortality was
      10.1% (n=182 [IQR 2.5-16.2) for emergent procedures. INTERPRETATION: POMR is
      frequently reported in LMICs, but a standardised approach for reporting and risk
      stratification is absent from the literature. There was wide variation in POMR
      across procedures and specialties. A quality assessment checklist for surgical
      mortality studies could improve mortality reporting and facilitate benchmarking
      across sites and countries. FUNDING: None.

PMID- 26313077
TI  - Demographics of patients affected by surgical disease in rural hospitals in two
      sub-Saharan African countries: a retrospective analysis.
AB  - BACKGROUND: Awareness is growing of both the importance of surgical disease as a
      major cause of death and disability in low-income and middle-income countries
      (LMICs) and the cost-effectiveness of fairly simple surgical interventions. We
      hypothesised that surgical disease predominantly affects young adults and is
      therefore significant in both the macroeconomic effect of untreated disease and
      the microeconomic effects on patients and families in low-resource settings.
      METHODS: We retrospectively reviewed all admission data from two rural government
      district hospitals, Bo District Hospital in Sierra Leone and Thyolo District
      Hospital in Malawi. Both hospitals serve a rural population of roughly 600 000.
      We analysed data from 3 months in the wet season and 3 months in the dry season
      for each hospital by careful analysis of all hospital logbook data. For the
      purposes of this study, a surgical diagnosis was defined as a diagnosis in which
      the patient should be managed by a surgically trained provider. We analysed all
      surgical admissions with respect to patient demographics (age and sex),
      diagnoses, and the procedures undertaken. FINDINGS: In Thyolo, 835 (12.9%) of
      6481 hospital admissions were surgical admissions. In Bo, 427 (19.8%) of 2152
      hospital admissions were surgical admissions. In Thyolo, if all patients who had
      undergone a procedure in theatre were admitted overnight, the total number of
      admissions would have been 6931, with 1344 (19.4%) hospital admissions being
      surgical and 1282 (18.5%) hospital patients requiring a surgical procedure. In
      Bo, 133 patients underwent a surgical procedure. This corresponded to 6.18% of
      all hospital admissions; although notably many of the obstetric admissions were
      referred to a nearby Medecins Sans Frontieres (MSF) hospital for treatment.
      Analysis of the admission data showed that younger than 16-year-olds accounted
      for 10.5% of surgical admissions in Bo, and 17.9% of surgical admissions in
      Thyolo. 16-35-year-olds accounted for 57.3% of all surgical admissions in Bo and
      53.5% of all surgical admissions in Thyolo. Men accounted for 53.7% of surgical
      admissions in Bo and 46.0% of surgical admissions in Thyolo. Analysis of the
      procedure data showed that younger than 16-year-olds accounted for 7.0% of
      procedures in Bo and 4.5% of procedures in Thyolo, with 16-35-year-olds
      accounting for 65.6% of all procedures in Bo and 84.4% of all procedures in
      Thyolo. Men underwent 63% of all surgical procedures in Bo, but only 7.7% of
      surgical procedures in Thyolo. This discrepancy is explained by the high rate of
      maternal surgery in Thyolo, which was not present in Bo because this service was
      provided at the nearby MSF hospital. INTERPRETATION: Most people affected by
      disease requiring surgery are young adults. It would be expected that failure to
      provide surgical care could have long-term adverse effects on both individual and
      national wealth. FUNDING: The Sir Ratanji Dalal Scholarship from the Royal
      College of Surgeons of England.

PMID- 26313078
TI  - Musculoskeletal trauma and all-cause mortality in India: a multicentre
      prospective cohort study.
AB  - BACKGROUND: There is little data in low-income and middle-income countries
      (LMICs) quantifying the burden of fractures and describing current practices. The
      aim of the study was describe the severity of musculoskeletal injuries in LMICS
      and identify modifiable factors that predict subsequent early all-cause
      mortality. METHODS: We did a multicentre, prospective, observational study of
      patients who presented to 14 hospitals across India for musculoskeletal trauma
      (fractures or dislocations). Patients were recruited during an 8-week period,
      between November, 2011, and June, 2012, and were followed for 30-days or hospital
      discharge, whichever occurred first. Primary outcome was all-cause mortality with
      secondary outcomes of reoperation and infection. Logistic regression analyses
      were conducted to identify factors associated with all-cause mortality. FINDINGS:
      We enrolled 4822 patients, but restricted analyses to 4612 (96%) patients who had
      complete follow-up. The majority (56.2% younger than 40 years old) of trauma
      patients were young (mean age 40.9 years [SD 16.9]) and 3148 (68%) were men. 2344
      (518%) patients sustained trauma as a result of a road traffic accident. The most
      common musculoskeletal injury was a fracture (4514 [98%]) and 707 patients (15%)
      incurred an open fracture. Less than a third of musculoskeletal trauma patients
      (1374 [29%]) were transported to hospital by ambulance, and one in six patients
      (18%) arrived at the hospital later than 24 h after sustaining their injury. Over
      a third (239 [35%] of 707) of open fractures were definitively stabilised later
      than 24 h. 30-day mortality was 1.7% (95% CI 1.4-2.2) for all patients and 2.1%
      (95% CI 1.5-2.7) among road traffic victims (p=0.005). Musculoskeletal trauma
      severity including the number of fractures (3.1 [95% CI 2.4-3.9]) and presence of
      an open fracture (2.1 [95% CI 1.2-3.4]) significantly increased the odds of all
      cause mortality. INTERPRETATION: Musculoskeletal trauma severity, particularly
      road related, is a key predictor of subsequent mortality. Improvement in road
      safety policies, and improvements in access to emergency medical services and
      timely orthopaedic care are critical to mitigate the burden of injury worldwide.
      FUNDING: Regional Medical Associates, AO International, Hamilton Health Sciences
      Trauma Fund.

PMID- 26313079
TI  - Care of surgical infections by Medecins Sans Frontieres Operations Centre
      Brussels in 2008-14.
AB  - BACKGROUND: Surgical infections represent a substantial yet undefined burden of
      disease in low-income and middle-income countries (LMICs). Medecins Sans
      Frontieres (MSF) provides surgical care in LMICs and collects data useful to
      describe the operative epidemiology of surgical need that would otherwise be
      unmet by national health services. We aimed to describe the experience of MSF
      Operations Centre Brussels surgery for infections during crisis; aid effective
      resource allocation; prepare humanitarian surgical staff; and further
      characterise unmet surgical needs in LMICs. METHODS: We reviewed all procedures
      undertaken in operating theatres at facilities run by the MSF Operations Centre
      Brussels between July, 2008, and June, 2014. Projects providing only specialty
      care were excluded. Procedures for infections were quantified, related to
      demographics and reason for humanitarian response was described. FINDINGS: 96 239
      operations were undertaken at 27 MSF Operations Centre Brussels sites in 15
      countries. Of 61 177 general operations, 7762 (13%) were for infections.
      Operations for skin and soft tissue infections were the most common (64%),
      followed by intra-abdominal (26%), orthopaedic (6%), and tropical infections
      (3%). The proportion of operations for skin and soft tissue infections was
      highest during natural disaster missions, intra-abdominal infections during
      hospital support missions, and orthopaedic infections during conflict missions.
      Most procedures for skin and soft tissue infections were minor (76%), whereas
      most operations for intra-abdominal infections were major (98%). INTERPRETATION:
      Surgical infections are among the most common causes for operation in LMICs.
      Although many procedures were minor, they represent substantial use of
      perioperative resources. Growing evidence shows the need for improved
      perioperative capacity to aptly care for the volume and variety of conditions
      comprising the global burden of surgical disease. FUNDING: Medecins Sans
      Frontieres.

PMID- 26313080
TI  - Deaths from acute abdominal conditions and geographic access to surgical care in
      India: a nationally representative population-based spatial analysis.
AB  - BACKGROUND: Acute abdominal conditions have high case-fatality rates in the
      absence of timely surgical care. In India, and many other low-income and middle
      income countries, few population-based studies have quantified mortality from
      surgical conditions and related mortality to access to surgical care. We aimed to
      describe the spatial and socioeconomic distributions of deaths from acute abdomen
      (DAA) in India and to quantify potential access to surgical facilities in
      relation to such deaths. METHODS: We examined deaths from acute abdominal
      conditions within a nationally representative, population-based mortality survey
      of 1.1 million Indian households and linked these to nationally representative
      facility data. Spatial clustering of deaths from acute abdominal conditions was
      calculated with the Getis-Ord Gi* statistic from about 4000 postal codes. We
      compared high or low acute abdominal mortality clusters for their geographic
      access to well-resourced surgical care (24 h surgical and anaesthesia services,
      blood bank, critical care beds, basic laboratory, and radiology). FINDINGS: 923
      (1.1%) of 86 806 study deaths in those aged 0-69 years were identified as deaths
      from acute abdominal conditions, corresponding to an estimated 72 000 deaths
      nationally in India in 2010. Most deaths occurred at home (71%), in rural areas
      (87%), and were caused by peptic ulcer disease (79%). There was wide variation in
      rates of deaths from acute abdominal conditions. We identified 393 high-mortality
      geographic clusters and 567 low-mortality clusters. High-mortality clusters of
      acute abdominal conditions were located significantly further from well-resourced
      hospitals than were low-mortality clusters. The odds ratio of a postal code area
      being a high-mortality cluster was 4.4 (99% CI 3.2-6.0) for living 50 km or more
      from well-resourced district hospitals (rising to an OR of 16.1 for >100 km),
      after adjustment for socioeconomic status and caste. INTERPRETATION: Improvements
      in human and physical resources at existing public hospitals are required to
      reduce deaths from acute abdominal conditions in India. Had all of the Indian
      population had access to well-resourced hospitals within 50 km, more than 50 000
      deaths from acute abdominal conditions could have been averted in 2010, and
      likely more from other emergency surgical conditions. Our geocoded facility data
      were limited to public district hospitals. However, noting the high rate of
      catastrophic health expenditures in India, we chose to focus on publicly provided
      services which are the only option usually available to the poor. FUNDING: The
      Bill & Melinda Gates Foundation, Dalla Lana School of Public Health, and Canadian
      Institute of Health Research.

PMID- 26313081
TI  - Avoidable maternal and neonatal deaths associated with improving access to
      caesarean delivery in countries with low caesarean delivery rates: an ecological
      modelling analysis.
AB  - BACKGROUND: Reducing maternal and neonatal deaths are important global health
      priorities. We have previously shown that up to a country-level caesarean
      delivery rate (CDRs) of roughly 19.0%, cesarean delivery rates and maternal
      mortality ratio (MMR) and neonatal mortality rate (NMR) were inversely
      correlated. We investigated the absolute reductions in maternal and neonatal
      deaths if countries with low CDR increased their rates to a range of greater than
      7.2% but less than or equal to 19.1%. METHODS: We calculated maternal and
      neonatal deaths in 2013 and 2012, respectively, for countries with CDR 7.2% or
      less (N=45) with available data from the World Bank Development Indicators. We
      modelled the expected reduction in deaths in these countries if they had the 25th
      and 75th MMR and NMR percentiles observed for countries (N=48) with CDRs ranging
      from greater than 7.2% but less than or equal to 19.1%. This model assumes that
      if countries with low CDRs increased their rates of caesarean delivery to greater
      than 7.2% but less than or equal to 19.1%, they would achieve levels of MMR and
      NMR observed in countries with those CDRs. FINDINGS: We estimate 176 078 (95% CI
      163 258-188 898) maternal and 1 117 257 (95% CI 1 033 611-1 200 902) neonatal
      deaths occurred in 45 countries with low CDRs in 2013 and 2012, respectively. If
      these countries had the 25th and 75th MMR and NMR percentiles (MMR, IQR 36-190;
      NMR, 9-24) observed in countries (N=48) with a CDR ranging from greater than 7.2%
      but less than or equal to 19.1%, there would be a potential reduction of 109 762
      163 513 and 279 584-803 129 maternal and neonatal deaths, respectively.
      INTERPRETATION: Increasing caesarean delivery in countries with low CDRs could
      avert as many as 163 513 maternal deaths and 803 129 neonatal deaths annually.
      These findings assume that as health systems develop the capacity to deliver
      surgical care, there is a concurrent improvement in the quality of care and in
      the ability to rescue women and neonates who would otherwise die. Improving
      access to safe caesarean delivery should be a central focus in surgical care
      globally. FUNDING: None.

PMID- 26313082
TI  - Variability in mortality after caesarean delivery, appendectomy, and groin hernia
      repair in low-income and middle-income countries: implications for expanding
      surgical services.
AB  - BACKGROUND: While surgical interventions occur at lower rates in resource-poor
      settings, rates of complication and death after surgery are substantial but have
      not been well quantified. A deeper understanding of outcomes is a crucial step to
      ensure that quality accompanies increased global access to surgical care. We
      aimed to assess mortality following surgery to assess the risks of such
      interventions in these environments. METHODS: We collected the most recent
      demographic, health, and economic data from WHO for 114 countries classified as
      low-income or lower-middle-income according to the World Bank in 2005. We
      searched OVID, MedLine, PubMed, and SCOPUS to identify studies in these countries
      reporting all-cause mortality after three commonly performed operations:
      caesarean delivery, appendectomy, and groin hernia repair. Reports from
      governmental and other agencies were also identified. We modelled surgical
      mortality rates for countries without reported data with the lasso technique that
      performs continuous variable subset selection to avoid model overfitting. We
      validated our model against known case fatality rates for caesarean delivery. We
      aggregated mortality results by subregion to account for variability in data
      availability. We then created collective surgical case fatality rates by WHO
      region. FINDINGS: We identified 42 countries with mortality data for at least one
      of the three procedures. Median reported mortality rates were 7.7 per 1000
      operations for caesarean delivery (IQR 3-14), 4.0 per 1000 operations for
      appendectomy (IQR 0-17), and 4.7 per 1000 operations for hernia groin (IQR 0-13);
      all recorded deaths occurred during the same admission to hospital as the
      operation. Based on our model, case fatality rate estimates by subregion ranged
      from 0.7 (central Europe) to 13.9 (central sub-Saharan Africa) per 1000 caesarean
      deliveries, 5.6 (central Asia) to 6.4 (central sub-Saharan Africa) per 1000
      appendectomies, and 3.5 (tropical Latin America) to 33.9 (central sub-Saharan
      Africa) per 1000 hernia repairs. INTERPRETATION: All-cause postoperative
      mortality rates are exceedingly variable within resource-constrained
      environments, and substantially higher than those in middle-income and high
      income settings. Efforts to expand surgical access and provision of services must
      include a strong commitment to improve the safety and quality of care. FUNDING:
      None.

PMID- 26313083
TI  - Neonatal surgery in Africa: a systematic review and meta-analysis of challenges
      of management and outcome.
AB  - BACKGROUND: Advances in diagnostic techniques and perioperative care have greatly
      improved the outcome of neonatal surgery. Despite this, disparity still exists in
      the outcome of neonatal surgery between high-income countries and low-income and
      middle-income countries. This study reviews publications on neonatal surgery in
      Africa over 20 years with a focus on challenges of management, trends in outcome,
      and potential interventions to improve outcome. METHODS: We did a literature
      review by searching PubMed and African Index Medicus for original articles
      published in any language between January, 1995, and September, 2014, with the
      search terms "neonatal surgery" and "Africa", further supplemented by "(surgery
      OR anaesthesia) AND (neonatal OR newborn) AND (developing countries OR Africa)".
      A data extraction sheet was used to collect information, including type of study,
      demographics, number of cases, outcome, challenges, and suggestions to improve
      outcome. For the meta-analysis, data were analysed by chi(2) test or Student's t
      test as appropriate. In all, the significance level was set to p<0.05. FINDINGS:
      We identified 859 published papers, of which 51 studies from 11 countries met the
      inclusion criteria. The 16 studies in the first 10 years (before 2005; group A)
      were compared with the 35 in the last 10 years (2005-14; group B). Nigeria (n=32;
      62.7%), South Africa (n=7; 13.7%), Tanzania (n=2; 3.9%), and Tunisia (n=2; 3.9%)
      were the predominant source of the publications, of which were retrospective in
      38 (74.5%) studies and prospective in 13 (25.5%) studies. The mean sample size of
      the studies was 97.8 (range 5-640). Overall, 4989 neonates were studied, with
      median age of 6 days (range 1-30). Common neonatal conditions reported were
      intestinal atresia in 28 (54.9%) studies, abdominal wall defects in 27 (52.9%),
      anorectal malformations in 24 (47.1%), and Hirschsprung's disease, necrotising
      enterocolitis, and volvulus neonatorum in 23 (45.1%) each. Mortality was lowest
      (<3%) in spina bifida and facial cleft procedures, and highest (>50%) in
      emergency neonatal surgeries involving bowel perforation, bowel resection,
      congenital diaphragmatic hernia, oesophageal atresia, and ruptured omphalocele or
      gastroschisis. Overall average mortality rate was higher in group A than in group
      B (36.9% vs 29.1%; p<0.001), but mortality did not vary between the groups for
      similar neonatal conditions. The major documented challenges were delayed
      presentation and inadequate facilities in 39 (76.5%) studies, dearth of trained
      support personnel in 32 (62.7%), and absence of neonatal intensive care in 29
      (56.9%). The challenges varied from country to country but did not differ in the
      two groups. INTERPRETATION: Improvement has been achieved in outcomes of neonatal
      surgery in Africa in the past two decades, although several of the studies
      reviewed are retrospective and poorly designed. Cost-effective adaptations for
      neonatal intensive care, improved health-care funding, coordinated neonatal
      surgical care via regional centres, and collaboration with international partners
      are potential interventions that could help to address the challenges and further
      improve outcome. FUNDING: None.

PMID- 26313084
TI  - Ultrasound guided transversus abdominis plane versus sham blocks after caesarean
      section in an Ugandan village hospital: a prospective, randomised, double
      blinded, single-centre study.
AB  - BACKGROUND: Transversus abdominis plane (TAP) block provides 12-24 h of analgesia
      to the parietal peritoneum and abdominal wall, and are best used combined with
      oral or intravenous medications. Despite ease of use, a large margin of safety,
      and a high success rate, TAP blocks remain under used in settings where patients
      could most benefit from their use. Previous studies have used oral or intravenous
      narcotics for supplementation. However, the efficacy of TAP blocks in low
      resourced settings where patients do not have dependable access to these
      medications is unknown. This study examines TAP block analgesic efficacy after
      caesarean section in a poorly resourced setting. We compared the post-operative
      status of 170 women with self-administered paracetamol-diclofenac with or without
      TAP blocks. We hypothesised that the block would decrease pain at 8 h, 16 h, and
      24 h at rest, with coughing and upon standing. METHODS: Between Oct 31, and Dec
      28, 2013, 180 women were enrolled and randomly assigned to receive either TAP or
      sham blocks after caesarean section. Bi-institutional (Mbarara Regional Referral
      Hospital and Massachusetts General Hospital) institutional review board approval
      was obtained for this single-centre study. After informed written consent,
      patients received TAP or sham blocks after caesarian section. Inclusion criteria
      for enrolment were: age 18 years or older, weight at least 50 kg, no allergies to
      study medications, otherwise healthy (American Society of Anesthesiologists
      classification status I or II), and having undergone elective, urgent, or
      emergent caesarian section under spinal anaesthesia without sedation. Under
      ultrasound guidance, 20-25 mL of 0.25% bupivacaine (epinephrine 1:400 000) were
      injected near the triangles-of-Petit. Sham blocks consisted of a transducer with
      a needleless syringe pressed over each flank. In the post-anaesthesia recovery
      area, all patients received 1000 mg paracetamol and 50 mg diclofenac, orally, to
      be continued on an 8-h schedule for 3 days. A skilled (masked) research nurse
      collected all data. The primary outcomes measured were numerical rating scale at
      8 h, 16 h, and 24 h at rest, with coughing, and upon standing. The association
      between the pain scores at each time and type of treatment (TAP vs sham blocks)
      was assessed using general linear model with repeated measures. Demographics were
      compared using the two sample t-test (appendix). FINDINGS: 170 patients completed
      the study; 86 in the sham group and 84 in the study group. Demographics (age,
      weight, and parity) were similar between both study groups. One participant from
      the sham group was missing parity information (appendix). Preliminary data
      analysis showed reduced pain scores at all times, and with all degrees of
      movement for the TAP group (appendix). The largest reduction in pain was at 8 h
      (resting 33%, coughing 36%, and standing 44%). With time, the pain scores of the
      TAP group changed a little, whereas a decreasing trend can be noted in the sham
      group. No adverse events occurred. INTERPRETATION: This study show a significant
      improvement in pain scores for obstetric patients receiving a transversus
      abdominis plane block in comparison to standard of care in a low income, limited
      resource setting. The use of these blocks shows the use of an easy, inexpensive,
      and achievable pain control option. Especially in resource-limited areas, this
      approach could allow for better pain management and a new standard of care for
      the world's most common operative procedure. FUNDING: Eleanor and Miles Harvard
      Medical School Shore Fellowship Grant, and Massachusetts General Hospital, DACCPM
      Faculty Development Grant.

PMID- 26313085
TI  - Palatal fistula risk after primary palatoplasty: a retrospective comparison of
      humanitarian operations and tertiary hospitals.
AB  - BACKGROUND: Humanitarian surgical organisations provide cleft palate repair for
      patients without access to surgical care. Despite decades of experience, very
      little research has assessed the outcomes of these trips. This study investigates
      the fistula rate in patients from two cohorts in rural China and one in the USA.
      METHODS: This retrospective study compared the odds of fistula presentation among
      three cohorts whose palates were repaired between April, 2005, and November,
      2009. The primary cohort included 97 Chinese patients operated on in China by
      surgeons from ReSurge International. A second Chinese cohort of 250 patients was
      operated on at Huaxi University Hospital by Chinese surgeons. The third cohort of
      120 patients from the University of California San Francisco (UCSF) was included
      for comparison over the same time period; data was taken from medical records.
      Age, fistula presentation, and Veau Class were compared between the three cohorts
      with chi(2) tests. Logistic regression was used to analyse predictors of fistula
      presentation among the three cohorts. This study received institutional review
      board approval from the UCSF, the Harvard School of Public Health, and physicians
      at Huaxi University Hospital, and written consent was obtained from study
      participants in China. FINDINGS: The fistula risk was 35.4% in ReSurge patients,
      12.8% for patients at Huaxi University Hospital, and 2.5% for patients at UCSF
      (p<0.001). At the time of surgery 15.5% of the ReSurge patients were younger than
      2 years old, whereas 90.8% of the UCSF children and 41.6% of the Huaxi children
      were (p<0.001). In the ReSurge cohort, 20.6% of patients had a Veau class of I or
      II, wheras 40.8% and 58.9% of UCSF and Huaxi patients, respectively, were in
      class I or II (p<0.001). Age and Veau Class were associated with fistula
      formation in a univariate analysis. (Veau Class III or IV vs I or II, odds ratio
      [OR] 6.399 [95% CI 3.182-12.871]; age, OR 1.071 [95% CI 1.024-1.122]). A
      multivariate model controlling for the surgical group, age at palatoplasty, and
      sex showed an association between Veau Class and the odds of fistula presentation
      (Class III or IV vs I or II, OR 5.630 [95% CI 2.677-11.837). In this model, UCSF
      patients and Huaxi patients had 0.064 and 0.451 times the odds of developing a
      fistula, respectively, compared with ReSurge patients (p<0.001 both).
      INTERPRETATION: Chinese children undergoing palatoplasty on surgical missions
      have higher post-operative odds of palatal fistula than do children treated by
      local physicians. Children in low-resource settings have higher complication
      rates than do children in high-resource settings. Older age at palatoplasty and a
      Veau class III and IV are associated with post-palatoplasty fistula. Furthermore
      demographic, socioeconomic, and cultural differences could play a part in
      palatoplasty fistula outcomes between these three populations. More research is
      needed to determine the effects of post-operative care, the skill of the
      providers, and the technique used in the surgery that play a role on fistula
      outcomes after primary palatoplasty, particularly in low-resource environments.
      FUNDING: None.

PMID- 26313086
TI  - Expansion of laparoscopic cholecystectomy in a resource limited setting,
      Mongolia: a 9-year cross-sectional retrospective review.
AB  - BACKGROUND: The benefits of laparoscopic cholecystectomy have been largely
      unavailable to most people in developing countries. Mongolia has an extremely
      high incidence of gallbladder disease. In 2005, only 2% of cholecystectomies were
      being done laparoscopically. Open cholecystectomies were associated with high
      rates of wound infections, complications, and increased recovery time. Because of
      the unacceptable complications associated with open cholecystectomies, and nearly
      50% of the nomadic population needing faster post-operative recovery times, a
      national project for the development of laparoscopic surgery was organised. Multi
      institutional collaboration between the Mongolia Health Sciences University, the
      Dr W C Swanson Family Foundation (SFF), the University of Utah, Intermountain
      Healthcare, and the Society of American Gastrointestinal and Endoscopic Surgeons
      (SAGES) led to the promulgation of a formalised countrywide laparoscopic training
      programme during the past 9 years. This is a retrospective review of the
      transition from open to laparoscopic cholecystectomy throughout Mongolia.
      METHODS: Demographic patient data, diagnosis, and operation preformed
      laparoscopic versus open cholecystectomy, between January, 2005, and September,
      2013, were collected and trends were analysed from seven regional diagnostic
      referral and treatment centres, and two tertiary academic medical centres from
      six of the 21 provinces (Aimags) throughout Mongolia. Data were analysed by
      individual training centre, by year, and then compared between rural and urban
      centres. FINDINGS: Nearly 16 000 cholecystectomies were analysed and compared
      (4417 [28.2%] men; 11 244 [71.8%] women). Men and women underwent laparoscopic
      cholecystectomy with the same frequency (41.2% men, 43.2% women) and had similar
      age (men, mean 52.2 years [SD 14.8]; women, mean 49.4 years [SD 15.7]). By 2013,
      62% of gallbladders were removed laparoscopically countrywide as opposed to only
      2% in 2005. More than 315 Mongolian practitioners have received laparoscopic
      training in 19 of 21 Aimags. On average 60% of cholecystectomies are done
      laparoscopically in urban surgical centres, up from 2%, versus 55% in rural
      surgical centres, up from 0%, in 2005. Laparoscopic cholecystectomy surpassed
      open cholecystectomy as the primary method for gallbladder removal countrywide in
      2011. INTERPRETATION: By 2013, 62% of cholecystectomies countrywide were done
      laparoscopically, a great increase from 9 years ago. Despite being a resource
      limited country, the expansion of laparoscopic cholecystectomy has transformed
      the care of biliary tract disease in Mongolia. FUNDING: The University of Utah
      Center for Global Surgery.

PMID- 26313087
TI  - General surgery education: a systematic review of training worldwide.
AB  - BACKGROUND: Surgical care is an essential component of health management
      worldwide. As the prevalence of injuries and non-communicable diseases increases,
      the provision of effective surgical care will become an increasingly important
      priority to reduce death and disability. To assess the ability of health systems
      to meet current surgical needs, we did a review of surgical training programmes
      worldwide. METHODS: We searched Medline, EMBASE, and the Global Health Library
      databases with the search terms "surgical training" and "surgeon training" for
      abstracts and citations in all languages published between Jan 1, 1998, and Dec
      31, 2013, describing a national general surgery training system. We extracted the
      following data: a brief description of the programme, years of training required,
      year after medical school graduation when training begins, name of national
      oversight organisation(s), in-country opportunities for subspecialty training,
      and whether programmes self-identified as being similar to or affected by the
      surgical education system in the USA or the UK. FINDINGS: We identified 5229
      abstracts (3888 from Medline, 971 from EMBASE, and 726 from the Global Health
      Library databases). 228 (4.4%) articles underwent full text review. 60 articles
      were included for data extraction. We identified descriptions of general surgery
      training programmes in 52 countries. Data from an additional 17 countries
      represented by a regional college of surgeons were also recorded. Training
      duration ranged from 2-8 years (median total training, 6 years; median surgical
      training, 5 years), and lasted on average 6 years after medical school
      graduation. 19 countries self-identified as being similar to or affected by the
      US or UK training model. Many low-income and middle-income countries (LMICs) are
      working to expand access to surgical care through programmes, often focusing on
      training non-physician clinicians. Programmes in high-income countries have also
      undergone substantial reforms, affected by evolving practice environments,
      trainee preferences, and training bottlenecks. INTERPRETATION: General surgery
      training programmes are often responsive to national health care needs. We show a
      global trend towards standardisation of curricula and competency-based training.
      Countries expanding or developing their programmes show benefit from association
      or partnership with larger surgical organisations and academic institutions, but
      there are questions of sustainability. Both LMICs and high-income countries stand
      to benefit from coordinating development of global training standards and
      educational exchanges. Although more research is needed to understand the role of
      surgical education in meeting the demand for surgical care, it is clear that a
      cross-nationally coordinated strategy will be important to address the burden of
      surgical disease. FUNDING: None.

PMID- 26313088
TI  - Rectal bleeding and endoscopy need in Sierra Leone: results of a nationwide,
      community-based survey.
AB  - BACKGROUND: Low-income and middle-income countries (LMICs) face a large burden of
      gastrointestinal diseases that benefit from prompt endoscopic diagnosis and
      treatment. This study aimed to estimate the prevalence of gross rectal bleeding
      among adults in Sierra Leone. METHODS: A cluster randomised, cross-sectional
      household survey using the SOSAS tool was undertaken in Sierra Leone. 75 clusters
      of 25 households with two randomly selected respondents in each were sampled to
      estimate the prevalence of and disability from rectal bleeding. Barriers to care
      were also assessed. FINDINGS: 3645 individuals responded to the survery, 15 with
      rectal bleeding. Nine responders (64%) had been bleeding for more than a year.
      The prevalence of rectal bleeding was 412 per 100 000 people. In view of these
      findings, an estimated 24 604 individuals with rectal bleeding are in need of
      evaluation in Sierra Leone. Eight (53%) of the 15 people with rectal bleeding
      sought care from a traditional healer. If medical care was not sought, the most
      common reason was absence of financial resources (ten people; 77%), followed by
      no capable facility availability (two; 15%), and inability to leave work or
      family for the time needed (one; 8%). Seven (54%) of those with rectal bleeding
      reported some form of disability, including five (39%) that had bleeding that
      prevented usual work. INTERPRETATION: The high prevalence of rectal bleeding
      identified in Sierra Leone represents a major unmet health-care need. This study
      did not examine the cause of bleeding. However, the high prevalence, chronicity,
      and disability among respondents with bleeding suggest a substantial burden of
      disease. Additionally, because microscopic haematochezia was not assessed, these
      data represent a bare-minimum estimate of rectal bleeding in need of evaluation
      and treatment. In view of the substantial burden of conditions that can be
      diagnosed, treated, or palliated with timely endoscopic therapy, it is
      appropriate to consider endoscopy among efforts to develop health system capacity
      in LMICs. FUNDING: Surgeons OverSeas, the Thompson Family Foundation, and the
      Fogarty International Center.

PMID- 26313089
TI  - Towards closing the gap of the global surgeon, anaesthesiologist, and
      obstetrician workforce: thresholds and projections towards 2030.
AB  - BACKGROUND: Billions of people are without access to surgical care, in part
      because of the inequitable distribution of the surgical workforce. Drawing on
      recently collected data for the number of surgeons, anaesthesiologists, and
      obstetricians worldwide, we sought to show their global maldistribution by
      identifying thresholds of surgical workforce densities, and by calculating the
      number of additional providers needed to reach those thresholds. METHODS: From
      the WHO Global Surgical Workforce Database, national data for the number of
      specialist surgeons, anaesthesiologists, and obstetricians per 100 000 population
      (density) were compared with the number of maternal deaths per 100 000 live
      births (maternal mortality ratio; MMR) in WHO member countries. A regression line
      was fit between density of specialist surgeons, anaesthesiologists, and
      obstetricians and the logarithm of MMR, and we explored the correlation for an
      upper and a lower density threshold. Based on previous estimates of the global
      volume of surgical procedures, a global average productivity per specialist was
      derived. We then multiplied the average productivity with the derived upper and
      lower threshold densities, and compared these numbers to previously estimated
      global need of surgical procedures (4664 procedures per 100 000 population).
      Finally, the numbers of additional providers needed to reach the thresholds in
      countries with a density below the respective threshold were calculated.
      FINDINGS: Each 10-unit increase in density of surgeons, anaesthesiologists, and
      obstetricians, corresponded to a 13.1% decrease in MMR (95% CI 11.3-14.8). We saw
      particularly steep improvements in MMR from 0 to roughly 20 per 100 000
      population. Above roughly 40 per 100 000 population, higher density was
      associated with relatively smaller improvements in MMR. These arbitrary
      thresholds of 20 and 40 specialists per 100 000 corresponded with a volume of
      surgery of 2917 and 5834 procedures per 100 000 population, respectively, and
      were symmetrically distributed around the estimated global need of 4664 surgical
      procedures per 100 000 population. Our density thresholds are slightly higher
      than the current average in lower-middle income countries (16 per 100 000) and
      upper-middle-income countries (38 per 100 000), respectively. To reach the
      threshold of at least 20 per 100 000 in each country today, another 440 231 (IQR
      438 900-443 245) providers would be needed. To reach 40 per 100 000, 1 110 610
      (IQR 1 095 376-1 183 525) providers would be needed. INTERPRETATION: Assuming
      uniform productivity, a global surgical workforce between 20 and 40 per 100 000
      would suffice to provide the world's missing surgical procedures. We concede that
      causality cannot be implied, but our results suggest that countries with a
      workforce density above certain thresholds have better health outcomes. Although
      the thresholds cannot be interpreted as a minimum standard, they are useful to
      characterise the global surgical workforce and its deficits. Such thresholds
      could also be used as markers for health system capacity. FUNDING: None.

PMID- 26313090
TI  - The scale-up of the surgical workforce.
AB  - BACKGROUND: Countries with fewer than 20 specialist surgeons, anaesthetists, and
      obstetricians (SAO) per 100 000 population have worse health outcomes. To achieve
      surgical workforce densities of 20 per 100 000 by 2030, a scale up of the
      surgical workforce is required. No previous study has shown what this will cost,
      how many providers will be required, or how long it will take to increase the
      global surgical workforce. We aim to identify these answers for health-care
      systems that employ SAO alone and for those that use a hybrid model of SAO and
      task shifting to inform strategic planning. METHODS: Data for the density of SAO
      per country were obtained from the WHO Global Surgical Workforce Database. To
      find the total number of SAO that need to enter the workforce by 2030 to achieve
      surgical workforce thresholds of 20 per 100 000, the population growth formula
      (P=0e(rt)) was used and we assumed exponential surgical workforce growth and two
      potential retirement rates of either 1% or 10%. We did not account for migration.
      The same calculations were used for associate clinicians needed to enter the
      workforce in either a 2:1 or 4:1 associate clinicians-to-SAO ratio. The costs to
      train SAO and associate clinicians were estimated with data for training costs
      imputed into a regression analysis with health-care expenditure per capita for
      each country. We assumed training costs will remain constant, and we did not
      account for inflation. The time needed to train new surgical and anaesthetic
      providers was estimated with average length of training for SAO and associate
      clinicians and was measured in person years. Two models (one for a system of SAO
      only and one for a hybrid of SAO and associate clinicians) were created to show
      how many providers will need to enter the workforce per year once training is
      complete to reach targets by 2030. The model did not involve the scale-up of the
      surgical workforce needed to address unmet needs of essential surgical services.
      FINDINGS: By 2030, the world will need 1 272 586 new surgical workforce providers
      to meet a surgical workforce density of 20 per 100 000 assuming a 1% retirement
      rate. This will cost US$71-146 billion depending on the model used. Low-income
      and lower-middle-income countries show the largest required scale-up. An
      additional 806 352 (median 3412 [IQR 691-6851]) providers are needed in those
      countries. In the SAO only model, this will cost a median of US$19.66 per 2013
      capita (IQR 15.79-25.07) and will take a median of 34 121 person years (IQR 6911
      68 509). In the 4:1 associate clinician-to-SAO ratio, it will cost a median of
      US$7.57 per capita and take 20 472 person years. When accounting for the delay of
      entry to the workforce due to training in these countries, the median rate of
      entry to meet the goal density will have to increase 10.9 times after a 10 year
      delay in an SAO only model as opposed to 4.98 times with a 5 year delay in the
      hybrid 4:1 associate clinician-to-SAO model. INTERPRETATION: Although low-income
      countries, lower-middle-income countries, and upper-middle-income countries will
      require a surgical workforce scale-up, lower-middle-income countries will require
      the largest scale-up. In these countries, implementing a system of task shifting
      can decrease costs and training times by 40%. Meeting densities of 20 per 100 000
      will not guarantee quality care or improved access in rural areas, and equal
      attention must be paid to the provision of safe, affordable, accessible surgical
      care to all who need it. FUNDING: None.

PMID- 26313091
TI  - Surgical care by non-surgeons in low-income and middle-income countries: a
      systematic review.
AB  - BACKGROUND: Anecdotal evidence suggests that task-shifting or the redistribution
      of responsibilities from fully-trained surgeons to clinicians with fewer
      qualifications could become a major component of surgical care delivery in many
      low-income and middle-income countries (LMICs). Our goal was to summarise the
      scope of surgical task-shifting in LMICs through a systematic review of the
      medical literature. METHODS: We searched PubMed, EMBASE, CINAHL, LILACS, and
      African Index Medicus databases for papers and abstracts published between 1975,
      and November, 2014, that provided original data regarding non-surgeon providers,
      the type and volume of operations they perform, and the outcomes they achieve.
      The search was done in English, French, Spanish, and Portuguese, and included
      terms related to surgery, non-physician providers, and LMIC country names.
      Outcomes included the number of non-physicians and non-surgeons practicing
      surgery in LMICs, their qualifications, practice models and locations, and the
      types and volume of operations performed. FINDINGS: We identified 65 articles and
      14 abstracts that described non-surgeon and non-physician providers performing 46
      types of surgical procedures, across eight surgical disciplines, in 41 LMICs.
      These procedures extended beyond those recommended by WHO, such as male
      circumcision and emergency obstetric surgery. Non-surgeons and non-physicians
      provided a large amount of surgical care in some locations, including 90% of
      obstretric surgeries, 38.5% of general surgery procedures, and 43% of non
      obstetric laparotomies at three separate hospitals. Of the 38 papers that
      specified urban or rural locations, 35 described task-shifting in rural areas or
      district hospitals. A variety of formal training models for surgical task
      shifting were noted, including collaborations between national governments, WHO,
      and private non-governmental organisations. Surgical providers often had no
      formal surgical training, and did not operate under the supervision of a fully
      trained provider. INTERPRETATION: Our results suggest that non-surgeon physicians
      and non-physician clinicians provide surgical care many in low-resource settings.
      A limitation of our study is that our search was conducted in only four
      languages. Because many studies described the same country, countries or regions
      in overlapping time frames, it was not possible to determine the total number of
      task-shifting providers. In view of the shortage of fully-trained surgeons in
      many LMICs, it seems likely that task-shifting is far more widespread than is
      indicated by the medical literature. More research is needed to accurately
      determine the full extent and implications of surgical task-shifting in LMICs
      worldwide. FUNDING: None.

PMID- 26313092
TI  - A multicountry health partnership programme to establish sustainable trauma
      training in east, central, and southern African countries using a cascading
      trauma management course model.
AB  - BACKGROUND: Injury accounts for 267 000 deaths annually in the nine College of
      Surgeons of East, Central, and Southern Africa (COSECSA-ASESA) countries, and the
      introduction of a sustainable standardised trauma training programme across all
      cadres is essential. We have delivered a primary trauma care (PTC) programme that
      encompasses both a "provider" and "training the trainers" course using a
      "cascading training model" across nine COSECSA countries. The first "primary
      course" in each country is delivered by a team of UK instructors, followed by
      "cascading courses" to more rural regions led by newly qualified local
      instructors, with mentorship provided by UK instructors. This study examines the
      programme's effectiveness in terms of knowledge, clinical confidence, and cost
      effectiveness. METHODS: We collected pre-training and post-training data from
      1030 candidates (119 clinical officers, 540 doctors, 260 nurses, and 111 medical
      students) trained over 28 courses (nine primary and 19 cascading courses) between
      Dec 5, 2012, and Dec 19, 2013. Knowledge was assessed with a validated PTC
      multiple choice questionnaire and clinical confidence ratings of eight trauma
      scenarios, measured against covariants of sex, age, clinical experience, job
      roles, country, and health institution's workload. FINDINGS: Post-training, a
      significant improvement was noted across all cadres in knowledge (19% [95% CI
      18.0-19.5]; p<0.05) and clinical confidence (22% [20.3-22.3]; p<0.05). Non
      doctors showed a greater improvement in knowledge (22% vs 16%; p<0.05) and
      confidence (24% vs 20%; p<0.05) than doctors. Candidates attending cascading
      courses also showed larger improvements in knowledge (21% vs 15%; p<0.002) and
      clinical confidence (23% vs 19%; p<0.002) than their primary course counterparts.
      Multivariate regression analysis showed that attending cascading courses
      (Coef=4.83, p<0.05), being a nurse (Coef=3.89, p=0.007) or a clinical officer
      (Coef=4.11, p=0.015), and attending a course in Kenya (Coef=9.55, p<0.002) or
      Tanzania (Coef=9.40, p<0.002) were strong predictors to improvement in multiple
      choice questionnaire performance. However, improvement in clinical confidence was
      affected by the job-role of the clinical officer (Coef=6.49, p=0.002) and
      attending a course in Kenya (Coef=16.12, p<0.02) or Tanzania (Coef=7.01, p<0.05).
      Cascading courses were on average L2000 less expensive than primary care courses.
      INTERPRETATION: To the best of our knowledge, this is the largest series in the
      literature on multicountry trauma management training in sub-Saharan Africa. Our
      study supports the concept of cascading courses as an educationally and cost
      effective method in delivering vital trauma training in low-resource settings led
      by local clinicians. FUNDING: Health Partnership Scheme through the UK Department
      for International Development (DFID).

PMID- 26313093
TI  - Who is performing surgery in low-income settings: a countrywide inventory of the
      surgical workforce distribution and scope of practice in Sierra Leone.
AB  - BACKGROUND: Scope of practice and in-country distribution of surgical providers
      in low-income countries remains insufficiently described. Through a nationwide
      comprehensive inventory of surgical procedures and providers in Sierra Leone, we
      aimed to present the geographic distribution, medical training, and productivity
      of surgical providers in a low-income country. METHODS: Following exhaustive
      sampling, a total of 60 facilities performing surgery in Sierra Leone 2012 was
      identified. Annual surgical activity was obtained from 58 (97%) facilities, while
      institution and workforce data was retrieved from 56 (93%). Characteristics of
      patients, facilities, procedures, and surgical providers were collected
      retrospectively from operation theatre logbooks and by interviewing facility
      directors. FINDINGS: In 2012, 164 full-time positions of surgical providers
      performed 24 152 surgeries in Sierra Leone. Of those, 58 (35.6%) were consultant
      surgeons, obstetricians, or gynaecologists (population density: 0.97 per 100 000
      inhabitants). 86 (52.9%) were medical doctors (1.42 per 100 000), whereas the 14
      (8.4%) associate clinicians and six (3.8%) nurses represented a density of 0.23
      and 0.10 per 100 000 inhabitants, respectively. Almost half of the districts
      (46%), representing more than 2 million people (34% of the population), had less
      than one fully trained consultant. Density of consultant and medical doctors were
      27 and six times higher in urban areas compared with rural areas, respectively.
      The surgical providers performed 144 surgeries per position in 2012 (2.8
      surgeries per week). Nurses performed 6.6% and associate clinicians 6.8% of the
      total national volume of surgeries. Districts with lower surgical rates had a
      significant lower productivity per surgical provider (Rho=0.650, p=0.022). We
      noted a significant positive correlation between the facility volume of surgery
      and the productivity of each surgical provider (p<0.001). INTERPRETATION:
      Surgical providers with higher qualifications seem to have a preference for urban
      settlements. Increasing the output of the existing workforce can contribute to
      expansion of surgical services. FUNDING: Norwegian University of Science and
      Technology.

PMID- 26313094
TI  - Delivering trauma training to multiple health-worker cadres in nine sub-Saharan
      African countries: lessons learnt from the COOL programme.
AB  - BACKGROUND: Africa has one of the highest road-traffic mortality rates in the
      world. Nurses and clinical officers play a pivotal part in trauma care as a
      result of substantial shortage of doctors. The COOL (COSECSA-Oxford-Orthopaedic
      Link) programme has delivered primary trauma care (PTC) training in nine sub
      Saharan African countries across a wide cadre of health-workers (540 doctors, 260
      nurses, 119 clinical officers, and 111 medical students). This prospective study
      investigates the effect of 28 consecutive PTCs and the training challenges that
      exist between different cadres and health institutions. METHODS: The course
      trains delegates in key trauma concepts: primary survey, airway management, chest
      injuries, major haemorrhage, and paediatric trauma. Candidates' knowledge of
      these concepts was assessed before and after the course with a validated 30
      Single-Best-Answer multiple choice questionnaire. Assessment scores were analysed
      by cadre, urban (383 candidates) or rural institutions (647 candidates), and sex
      (657 men, 373 women). A concept was categorised as being poorly understood when
      half the candidates achieved less than 50% of the correct answers. Descriptive
      statistics and MANOVA analysis were used, with an alpha level set at 0.05.
      FINDINGS: 1030 PTC providers were trained between Dec 5, 2012, and Dec 19, 2013.
      There was significant increase in multiple choice questionnaire (58% to 77%,
      p<0.05) and clinical confidence (68% to 90%, p<0.05) scores among delegates post
      course, with independent covariants of institution location and cadre
      significantly affecting post-course scores. Doctors achieved satisfactory scores
      on all key concepts (67% to 84%, p<0.05). Clinical officers (all concepts 53% to
      76%, p<0.05) particularly struggled with paediatric trauma (94 candidates <50%,
      mean 24.23 [95% CI 19-30]). Nurses (all concepts 42% to 64%, p<0.05) had
      difficulty with chest injuries (203 pre-course to 153 post-course candidates
      <50%, mean 49% [95% CI 45-52]) and paediatric trauma (212 pre-course to 161 post
      course candidates <=50%, post course mean 46% [95% CI 43-53]). Medical students
      achieved satisfactory scores in all concepts (overall 53% to 74%, p<0.05). Health
      workers based in urban hospitals (82%) outperformed those in rural hospitals
      (72%) (p=0.001) and sex had no significant effect on performance (p=0.07).
      INTERPRETATION: Our study shows that PTC courses led to improvement in trauma
      management knowledge and clinical confidence among a wide cadre of health
      workers. However, these are new concepts for many front-line health-workers, and
      regular refresher training will be required. There is also a difference in
      understanding of key trauma concepts among the different cadres. Future training
      in this region should address areas of weakness unique to each cadre,
      particularly paediatric trauma care. FUNDING: Health Partnership Scheme through
      the UK Department for International Development (DFID).

PMID- 26313095
TI  - Global surgical and anaesthetic task shifting: a systematic literature review and
      survey.
AB  - BACKGROUND: Billions of people worldwide lack access to surgical care; this is in
      part driven by severe shortages in the global surgical workforce. Task shifting,
      the movement of tasks to associate clinicians or non-specialist physicians, is a
      commonly implemented yet often contentious strategy to expand the surgical
      workforce. A more complete understanding of the global distribution and use of
      surgical and anaesthetic task shifting is needed to strengthen strategic planning
      efforts to bridge the gap between surgical and anaesthetic providers. We aimed to
      document the use of task shifting worldwide with an in-depth review of the
      literature and subsequent confirmation of practices through a provider survey.
      METHODS: We did a literature search according to PRISMA guidelines. We searched
      PubMed, Embase, The Cochrane Library, CINAHL, WHOLIS, and five regional databases
      for journal articles published between Jan 1, 1995, and Aug 29, 2014, for titles
      or abstracts mentioning surgical or anaesthetic care provision by associate
      clinicians or non-specialist physicians. We also searched article references and
      online resources. We extracted data for health cadres performing task shifting,
      the types of tasks performed, training programmes, and supervision of those
      performing tasks and compared these across regions and income groups.
      Additionally, we then undertook an unvalidated survey to investigate the use of
      task shifting at the country level, which was sent to surgeons and anaesthetists
      in 19 countries across all major regions of the world. FINDINGS: We identified 62
      studies. The review and survey provided data for 163 and 51 countries
      respectively, totalling 174 countries. Surgical task shifting occured in 30 (33%)
      of 92 countries. Anaesthetic task shifting occured in 108 (65%) of 165 countries.
      Task shifting was documented across all World Bank income groups. Where relevant
      data were available, in high-income countries, associate clinicians were commonly
      supervised (100% [four countries] for surgery and 90% [20 countries] for
      anaesthesia). In low-income countries, associate clinicians undertook surgical
      and anaesthetic procedures without supervision (100% for surgery [five countries]
      and 100% for anaesthesia [22 countries]). INTERPRETATION: Task shifting is used
      to augment the global surgical workforce across all geographical regions and
      income groups. Associate clinicians are ubiquitous among the global surgical
      workforce and should be considered in plans to scale up the surgical workforce in
      countries with workforce shortages. Reporting bias is likely to have favoured the
      more novel and successful task shifting initiatives, which could have caused our
      results to underestimate the absolute number of countries that use task shifting.
      Although surgical and anaesthetic task shifting has been described in many
      countries, further research is required to assess outcomes, especially in low
      income and middle-income countries where supervision is less robust. FUNDING:
      None.

PMID- 26313096
TI  - Community health workers and smartphones for the detection of surgical site
      infections in rural Haiti: a pilot study.
AB  - BACKGROUND: Absence of outcome data is a barrier to quality improvement in
      resource poor settings. To address this challenge, we set out to determine
      whether follow up for surgical site infections (SSIs) using community health
      workers (CHWs) and smartphones is feasible in rural Haiti. METHODS: In this pilot
      study, all patients from a specific mountain region who received an operation
      between March 10, and July 1, 2014, at Hopital Albert Schweitzer in rural Haiti
      were eligible for inclusion. Patients or guardians of minors were approached for
      consent. We designed a smartphone application to enable CHWs to screen for SSIs
      during home visits by administering a questionnaire, obtaining GPS data, and
      submitting a photograph of an incision. We selected and trained CHWs to use the
      smartphone application and compensated them based on performance. CHWs completed
      home visits for 30 days after an operation for all participants. Surgeons
      examined all participants within 24 h after the second CHW home visit. Primary
      outcomes included the number of participants completing 30-day follow-up and home
      visits made on time. Secondary outcomes included the quality of the photographs
      and the agreement between surgeons and CHWs on the diagnosis of SSI. The Partners
      Healthcare institutional review board and the Ethics Committee at Hopital Albert
      Schweitzer approved the study protocol. FINDINGS: Five CHWs completed 30-day
      follow up for 37 of 39 participants (94.9%) and completed 107 of 117 home visits
      on time (91.5%). High quality photographs were submitted for 101 of 117 visits
      (86.3%). Surgeons and CHWs agreed on the diagnosis of SSI in 28 of 33 cases
      (84.8%). INTERPRETATION: Outpatient follow up for SSIs with CHWs and smartphones
      is feasible in rural Haiti. Further validation of the programme needs to be done
      before widespread adoption or advocating for task shifting post-operative follow
      up to CHWs. FUNDING: Partners Healthcare, Children's Hospital Boston, and Swiss
      Bundner Partnerschaft Hopital Albert Schweitzer Haiti.

PMID- 26313097
TI  - Out-of-pocket expenses incurred by patients obtaining free breast cancer care in
      Haiti.
AB  - BACKGROUND: Women with breast cancer in low-income and middle-income countries
      (LMICs) account for 51% of cases globally and often present with advanced
      disease. Fear of costs contributes to delay in seeking care, as health
      expenditures are financially catastrophic for families worldwide. Despite efforts
      to improve affordability of health care in LMICs, the financial burden of
      indirect costs (eg, transportation and lost wages) is often overlooked. We aimed
      to identify and quantify the expenditures of patients seeking breast cancer care
      in a LMIC. METHODS: Patients receiving breast cancer care free of charge at
      Hopital Universitaire de Mirebalais (HUM) in Haiti were interviewed to quantify
      their costs and assess the effect of these costs on patients and families. These
      costs included expenses for food, lodging, transportation, childcare, medical
      costs at other institutions, and lost wages. 61 patients were interviewed during
      diagnostic, chemotherapy, and surgical visits between March 1, and May 12, 2014.
      Institutional review board exemption was granted from Boston Children's Hospital
      and Partners in Health/Zanmi Lasante. FINDINGS: The median non-medical out-of
      pockent expenses incurred by breast cancer patients at HUM were US$233 (95% CI
      170-304) for diagnostic visits, US$259 (95% CI 200-533) for chemotherapy, and
      US$38 (95% CI 23-140) for surgery. The median total out-of-pockent expense
      (including medical costs) was US$717 (95% CI 619-1171). These costs forced 52% of
      participants into debt and 20% to sell possessions. The median percentage of
      potential individual income spent on out-of-pocket costs was 60%. The median sum
      of out-of-pocket costs and lost wages was US$2996 (95% CI 1676-5179).
      INTERPRETATION: In Haiti, 74% of people earn less than US$2 per day. Even when
      breast cancer treatment is provided for free, out-of-pocket expenses could
      account for more than 91% of annual earnings at this income level. This financial
      burden is an overwhelming obstacle for Haiti's poorest citizens, and probably for
      many patients in LMICs. High-powered, multisite studies are needed to further
      characterise this burden worldwide. Funders and health-care providers should
      reduce indirect costs to achieve equitable access to oncology care. FUNDING:
      Boston Children's Hospital and Partners in Health.

PMID- 26313098
TI  - An analysis of out-of-pocket costs associated with hospitalised injuries in
      Vietnam.
AB  - BACKGROUND: Injuries create major financial burden for families. In this study,
      we estimated the distribution of out-of-pocket payment for medical care of
      injuries and the role of health insurance in containing such costs. METHODS: A
      prospective cohort study of 892 injured patients admitted to a provincial general
      hospital between Jan 1, 2010, and Aug 31, 2010, in Vietnam was done. Data for
      demographic, injury characteristics, and costs by specific categories paid out-of
      pocket by patients were included in the analyses. Generalised linear models with
      log link and gamma distribution were used to examine the associations between
      insurance status and total medical care costs and specific cost component.
      FINDINGS: The average total medical care costs paid out-of-pocket by patients
      during hospital stays were greater than US$270 (SD 193). Major drivers of total
      medical care costs related to surgery (nearly 25%), diagnostic tests or
      examinations (24%), and drugs (23%). Burn injuries incurred the highest medical
      care costs during hospital stays (mean US$321 [SD 179]) and assault incurred the
      lowest costs (mean US$167 [SD 165]). Total costs were higher for more severe
      injuries and those that required a higher level of surgery (from US$122 for
      maximum abbreviated injury score [MAIS] of 1 to US$485 to MAIS of 5; and US$194
      for non-surgery, US$202 for minor surgery, and US$428 for major surgery).
      Patients using health insurance had lower total costs than those who did not
      (US$245 vs US$279). However, no significant associations were noted between
      health insurance and total costs (p=0.142), costs for surgery (p=0.154),
      diagnostic tests or examinations (p=0.689), or drugs (p=0.341). INTERPRETATION:
      This study provides estimates and distribution of costs of medical care for
      injuries in hospital. Patients and their families seemed to bear all or most of
      these costs. Although the study highlights the need for ongoing efforts in injury
      prevention, it also provides further evidence on the few benefits of health
      insurance in protecting patients and their families from the high costs of
      hospital stays in Vietnam. FUNDING: Atlantic Philanthropies.

PMID- 26313099
TI  - Surgical need in an ageing population: a cluster-based household survey in Nepal.
AB  - BACKGROUND: With an ageing global population comes major non-communicable disease
      burden, especially in low-income and middle-income countries. An unknown
      proportion of this burden is treatable or palliated with surgery. This study
      aimed to estimate the surgical needs of individuals aged 50 years or older in
      Nepal. METHODS: A two-stage, 30 randomised cluster by 30 households, community
      based survey was performed in Nepal with the validated Surgeons OverSeas
      Assessment of Surgical Need (SOSAS). Respondents aged older than 50 years were
      included. After verbal informed consent was obtained, SOSAS collected household
      demographics, completed a verbal autopsy, and randomly selected household members
      for verbal head-to-toe examinations for surgical conditions. The Nepal Health
      Research Council in Kathmandu and the Nationwide Children's Hospital in Columbus,
      OH, USA, granted ethical approval. FINDINGS: The survey sampled 1350 households,
      totalling 2695 individuals (97% response rate); 49% were aged 50-59 years, 33%
      were 60-69 years, and 17% were 70 years and older. Of these, 273 surgical
      conditions were reported by 507 individuals. A growth or mass (including hernias
      and goiters) was the most commonly reported potentially surgical condition (25%),
      injuries and fractures were also common and had the greatest disability. Acquired
      deformities (13%), incontinence (11%), non-injury wounds (9%), and pelvic organ
      prolapse were also prevalent. Together, head and neck (24%) and back and
      extremity conditions (32%) were responsible for more than half of the conditions
      potentially treatable with surgery. These were followed by genitourinary (28%),
      abdominal (14%) and chest and breast conditions (2%). Extrapolated nationwide,
      roughly 1.25 million elderly individuals have a surgically treatable condition
      (32 150 per 100 000 people). There were 108 deaths in the year before to the
      survey. 20 (19%) were potentially preventable with surgery. Half of the deaths
      were due to a growth or mass, 20% to injury, 20% to abdominal pain or distension,
      and 10% to a non-injury wound. The age-standardised death rate of those with a
      potentially surgical condition was 24 per 1000 persons for individuals in their
      6th decadte, 60 per 1000 for those in their 7th, and 44 per 1000 for those in
      their 8th. One in five deaths were potentially treatable or palliated by surgery.
      Literacy and distance to secondary and tertiary health facilities were associated
      with not receiving care for surgical conditions (p<0.05). INTERPRETATION:
      Surgical need is largely unmet among elderly individuals in Nepal. Literacy and
      distance from a capable health facility are the greatest barriers to care.
      Although verbal examination findings were used as proxies for surgical
      conditions, the survey tool has been previously validated. Also, there is
      potential for recall bias with overestimation of tragic deaths and
      underestimation of unknown or forgotten surgical causes of death and disease.
      However, this is the most comprehensive evaluation of surgical need in a
      developing country among the elderly. As the global population ages, there is an
      increasing need to improve access to surgical services and strengthen health
      systems to care for this group. FUNDING: The Association for Academic Surgery,
      Surgeons OverSeas, and the Fogarty International Center.

PMID- 26313100
TI  - Cost of surgery and catastrophic expenditure in people admitted to hospital for
      injuries: estimates from a cohort study in Vietnam.
AB  - BACKGROUND: Little is known of the effect that surgery has on out-of-pocket
      health-care expenditure or on catastrophic health payments in low-income
      settings. Our study aims to estimate the surgery cost paid out-of-pocket by
      injury patients admitted to a provincial hospital in Vietnam and the risk of
      catastrophic expenditure at 12 months after discharge. METHODS: We conducted a
      prospective cohort study in a provincial hospital in Vietnam. Participants were
      patients admitted to hospital due to injuries, aged 18 years or older, had a
      current residential address in the province (Thai Binh province), and consented
      to participate in the study. We collected data during hospital stay and at 1
      month, 2 months, 4 months, and 12 months after discharge. Out-of-pocket costs
      incurred by injured people and their caregivers associated with care and
      treatment were collected. These covered all direct expenses incurred during
      hospital stay (surgery, emergency department, diagnostic examinations,
      medication, equipment, transportation, hospital stay, and others-eg, meals for
      both participants and their caretakers) and during follow-up (ongoing health
      checks, medication, meals, and transportation to outpatient clinic). Cost data
      were collected from the hospital bill and collected during face-to-face
      interviews with participants and their caretakers. The main outcome variables
      were surgery during hospital stay, total out-of-pocket payment, and catastrophic
      expenditure, defined as the out-of-pocket payment exceeding 40% of non
      subsistence spending, by 12-month follow-up. Modified Poisson regression was used
      to determine the association between surgery and the risk of catastrophic
      expenditure. FINDINGS: Of 892 participants recruited during admissions to
      hospital, surgery was undertaken in 634 participants, including 354 minor (40%)
      and 280 major (31%) surgeries. The mean costs of major and minor surgery were
      US$129 (SD 90) or 30.0% of the total medical care costs during hospital stays and
      US$68 (SD 41) or 33.6%, respectively. By 12 month follow-up, mean total direct
      out-of-pocket costs was US$625 (SD 603). Of 732 participants, 432 (59%) faced
      catastrophic expenditure. Specifically, this was 84% among those with major
      surgery, 47% with minor surgery, and 48% with no surgery. Compared with those
      with no surgery, the adjusted risk of catastrophic expenditure was only
      significantly higher for those had major surgery (RR 1.45 [95% CI 1.24-1.69]).
      INTERPRETATION: Costs of surgery create substantial financial burden for people
      admitted to hospital for injuries in Vietnam; although major surgery accounting
      for around 30% of total medical costs it is strongly associated with risk of
      catastrophic health payments. Although injury prevention efforts need greater
      investment, there is also a need to reform health-care insurance mechanisms to
      minimise the impact of out-of-pocket costs. FUNDING: Atlantic Philanthropies.

PMID- 26313101
TI  - Funding flows to global surgery: an analysis of contributions from the USA.
AB  - BACKGROUND: In recent years, funds for global health have risen substantially,
      particularly for infectious diseases. Although conditions amenable to surgery
      account for 28% of the global burden of disease, the external funds directed
      towards global surgical delivery, capacity building, and research are currently
      unknown and presumed to be low. We aimed to describe external funds given to
      these efforts from the USA, the world's largest donor nation. METHODS: We
      searched the United States Agency for International Development (USAID), National
      Institute of Health (NIH), Foundation Center, and registered US charitable
      organisations databases for financial data on any giving exclusively to surgical
      care in low-income and middle-income countries (LMICs). All nominal dollars were
      adjusted for inflation by converting to 2014 US dollars. FINDINGS: After
      adjustment for inflation, 22 NIH funded projects (totalling US$31.3 million, 1991
      2014) were identified; 78.9% for trauma and injury, 12.5% for general surgery,
      and 8.6% for ophthalmology. Six relevant USAID projects were identified; all
      related to obstetric fistula care totalling US$438 million (2006-13). US$105
      million (2003-13) was given to universities and charitable organisations by US
      foundations for 14 different surgical specialties (ophthalmology, cleft
      lip/palate, multidisciplinary teams, orthopaedics, cardiac, paediatric,
      reconstructive, obstetric fistula, neurosurgery, burn, general surgery, obstetric
      emergency procedures, anaesthesia, and unspecified specialty). 95 US charitable
      organisations representing 14 specialties (ophthalmology, cleft lip/palate,
      multidisciplinary teams, orthopaedics, cardiac, paediatric, reconstructive,
      obstetric fistula, neurosurgery, urology, ENT, craniofacial, burn, and general
      surgery) totalled revenue of US$2.67 billion and expenditure of US$2.5 billion
      (2007-13). INTERPRETATION: A strong surgical system is an indispensable part of
      any health system and requires financial investment. Tracking funds targeting
      surgery helps not only to quantify and clarify this investment, but also to
      ultimately serve as a platform to integrate surgical spending within health
      system strengthening. Although USAID is a vital foreign aid service and the NIH
      is a leader in biomedical and health research, their surgical scopes are
      restricted both financially (less than 1% of respective total budgets over the
      study years) and in surgical specialty. By contrast, the private charitable
      sector has contributed more financially and to more specialties. Still, current
      financial global health databases do not have precise data for surgery. To
      improve population health in LMICs, more resources should be dedicated to
      surgical system strengthening. Furthermore, exact classification measures should
      be implemented to track these important resources. FUNDING: None.

PMID- 26313102
TI  - Financial contribution to global surgery: an analysis of 160 international
      charitable organisations.
AB  - BACKGROUND: The non-profit and volunteer sector provides substantial
      contributions to global health. Within the field of surgery, this sector has made
      notable service contributions in low-income and middle-income countries (LMICs)
      where access to surgical care is poor. Little is known about financing and
      funding flows to surgical care in LMICs from both domestic and international
      sources. Because an estimated 55% of surgical care delivered in LMICs is via
      charitable organisations, understanding the financial contributions of this
      sector could provide valuable insight into estimating funding flows and
      understanding financing priorities in global surgery. METHODS: Between June, and
      September, 2014, we searched public online databases of registered charitable
      organisations in five high-income nations (the USA, the UK, Canada, Australia,
      and New Zealand) to identify organisations committed exclusively to surgical
      needs. Based on availability, the most current 5 years (2007-13) of financial
      data per organisation were collected. For each charitable organisation, we
      identified the type of surgical services provided. We examined revenues and
      expenditures for each organisation. FINDINGS: 160 organisations representing 15
      different surgical specialties were included in the analysis. Total aggregated
      revenue over the years 2008-2013 was US$3.3 billion. Total aggregated expenses
      for all 160 organisations amounted to US$3.0 billion. 28 ophthalmology
      organisations accounted for 45% of revenue and 49% of expenses. 15 cleft lip and
      palate organisations totalled 26% of both revenue and expenses. 19 organisations
      providing a mix of diverse surgical specialty services amounted to 14% of revenue
      and 16% of expenses. The remaining 15% of funds represented 12 specialties and 98
      organisations. The US accounted for 77.7% of revenue and 80.8% of expenses. The
      UK accounted for 11.0% of revenue and 11.91% of expenses. Canada accounted for
      1.85% of revenue and 2.01% of expenses. Australia and New Zealand accounted for
      4.94% of revenue and 5.29% of expenses. INTERPRETATION: Charitable organisations
      addressing surgical conditions primarily focus on elective surgical care and
      cover a broad range of subspecialties. The largest funding flows from charitable
      organisations are directed at ophthalmology, followed by cleft lip and palate
      surgery. However, there is a clear need for improved, transparent tracking of
      funds to global surgery via charitable organisations. FUNDING: None.

PMID- 26313103
TI  - Prioritisation of surgery in the National Health Strategic Plans of Africa: a
      systematic review.
AB  - BACKGROUND: Disease amenable to surgical intervention accounts for 11-15% of
      world disability and there is increasing interest in surgery as a global public
      health issue. National Health Strategic Plans (NHSPs) have been established in
      most countries and reflect their long-term health priorities, plans, and targets.
      To assess surgery's perceived importance in Africa, we reviewed its place in all
      such available plans. METHODS: We analysed all 43 of the 55 independent countries
      in Africa that had NHSPs available in the public domain in March, 2014, in
      English or French. We searched for policies electronically with the search terms
      "surg*", "ortho*", "trauma", "cancer", "appendic*", "laparotomy", "HIV",
      "tuberculosis", and "malaria" and included those from 2002 to 2030. We then
      searched manually for disease prevalence, targets, and human resources. FINDINGS:
      Eight (19%)of 43 NHSPs had no mention of surgery or surgical conditions. 28 (65%)
      of 43 had five or less mentions of surgery. HIV and malaria had 3801 mentions
      across all the policies compared with surgery with only 379 mentions. Trauma had
      243 mentions, while the common surgical conditions of appendicitis, laparotomy,
      and hernia had no mentions at all. More than 95% (41 of 43) of NHSPs specifically
      mentioned the prevalences of HIV, tuberculosis, malaria, infant mortality, and
      maternal mortality. The most commonly mentioned surgical condition for which a
      prevalence was given was trauma, in only 47% (23 of 43) of policies. All NHSPs
      had plans and measurable targets for the reduction of HIV and tuberculosis and
      all but one had targets for malaria, maternal mortality, and child mortality. Of
      the 4232 health targets across 43 NHSPs, only 96 (2.3%) were related to surgical
      conditions or surgical care. 14 (33%) of 43 policies had no surgical targets.
      INTERPRETATION: NHSPs are the best available measure of health service and
      planning priorities. It is clear from our findings that surgery is poorly
      represented and that surgical conditions and surgical treatment are not widely
      recognised as a public health priority. A paradigm shift is required if surgery
      is to be considered a public health concern, which should include greater
      prioritisation in national health strategic policies. FUNDING: None.

PMID- 26313105
TI  - Mapping the playing field-a novel web-based strategy to identify non-governmental
      actors in global surgery.
AB  - BACKGROUND: In the face of staggering global unmet need for surgical care, non
      governmental organisations (NGOs) play a substantial part in the surgical
      workforce, providing surgical care for those who are without it. The number of
      NGOs providing surgical care in low-income and middle-income countries (LMICs) is
      unknown. This information is needed to determine the scope of such care, its
      contributions to global surgical case volume, to improve collaboration in an
      effort to maximise efficiency, and to inform national surgical workforce
      planning. We aimed to create a comprehensive, publicly available catalogue of
      NGOs providing surgery in LMICs. METHODS: We used the United Nations Rule Of Law
      definition to define NGOs. We included low-income, lower-middle- income, and
      upper-middle-income countries as defined by World Bank lending groups. Delivery
      of surgical care by an NGO was defined as the therapeutic manipulation of tissues
      taking place within an operating room, and was distinguished from the financial
      or logistical support of such care. We screened an online humanitarian clearing
      house (ReliefWeb), a large public NGO database (Idealist.org), two surgical
      volunteerism databases (Operation Giving Back and the Society for Pediatric
      Anesthesia), and the US State Department Private Volunteer Organizations
      database, did a review of the literature, and used a social media outlet
      (Twitter) to identify organisations meeting criteria for inclusion. A
      complementary analysis additionally provided a list of organisations delivering
      exclusively surgical care from a search of the OmniMed database, the Foundation
      Center Online Directory, UK Charity Commission, Australia Charity Commission, New
      Zealand Charity Commission, and the Canada Revenue Agency Charity Search.
      FINDINGS: We identified 313 unique organisations, working in all 139 LMICs.
      Organisations often used more than one model of care and engaged in several
      surgical specialties. Both short-term surgical missions (206 organisations, 66%)
      and long-term partnerships (213, 68%) were common models, with 40 organisations
      (13%) engaging in humanitarian interventions in crisis settings. The most
      commonly represented specialty was general surgery (120, 38%), but subspecialty
      surgery such as ophthalmology (88, 28%) and cleft lip and palate surgery (70,
      22%) were also frequently performed. INTERPRETATION: To our knowledge, this is
      the most complete directory of NGOs undertaking surgery in resource-limited
      settings in existence. However, it is difficult to determine whether this review
      is exhaustive. Further work is needed to determine the total and relative
      contributions of these organisations to global surgical volume. This database
      will be made available for public use and should be maintained and updated to
      further coordinate global efforts and maximise impact. FUNDING: None.

PMID- 26313104
TI  - Generation of national political priority for surgery: a qualitative case study
      of three low-income and middle-income countries.
AB  - BACKGROUND: Surgical conditions exert a major health burden in low-income and
      middle-income countries (LMICs), yet surgery remains a low priority on national
      health agendas. Little is known about the national factors that influence whether
      surgery is prioritised in LMICs. We investigated factors that could facilitate or
      prevent surgery from being a health priority in three LMICs. METHODS: We
      undertook three country case studies in Papua New Guinea, Uganda, and Sierra
      Leone, using a qualitative process-tracing method. In total 72 semi-structured
      interviews were conducted between March and June, 2014, in the three countries.
      Interviews were designed to query informants' attitudes, values, and beliefs
      about how and why different health issues, including surgical care, were
      prioritised within their country. Informants were providers, policy makers, civil
      society, funders, and other stakeholders involved with health agenda setting and
      surgical care. Interviews were analysed with Dedoose, a qualitative data analysis
      tool. Themes were organised into a conceptual framework adapted from Shiffman and
      Smith to assess the factors that affected whether surgery was prioritised.
      FINDINGS: In all three countries, effective political and surgical leadership,
      access to country-specific surgical disease indicators, and higher domestic
      health expenditures are facilitating factors that promote surgical care on
      national health agendas. Competing health and policy interests and poor framing
      of the need for surgery prevent the issue from receiving more attention. In Papua
      New Guinea, surgical care is a moderate-to-high health priority. Surgical care is
      embedded in the national health plan and there are influential leaders with
      surgical interests. Surgical care is a low-to-moderate health priority in Uganda.
      Ineffectively used policy windows and little national data on surgical disease
      have impeded efforts to increase priority for surgery. Surgical care remains a
      low health priority in Sierra Leone. Resource constraints and competing health
      priorities, such as infectious disease challenges, prevent surgery from receiving
      attention. INTERPRETATION: Priority for surgery on national health agendas varies
      across LMICs. Increasing dialogue between surgical providers and political
      leaders can increase the power of actors who advocate for surgical care. Greater
      emphasis on the importance of surgical care in achieving national health goals
      can strengthen internal and external framing of the issue. Growing political
      recognition of non-communicable diseases provides a favourable political context
      to increase attention for surgery. Lastly, increasing internally generated issue
      characteristics, such as improved tracking of national surgical indicators, could
      increase the priority given to surgery within LMICs. FUNDING: The Bill & Melinda
      Gates Foundation, King's Health Partners/King's College London, and Lund
      University.

PMID- 26313106
TI  - Head and neck cancer in South Asia: macroeconomic consequences and the role of
      surgery.
AB  - BACKGROUND: Head and neck cancer, for which the diagnosis and treatment are often
      surgical, comprises a substantial proportion of the burden of disease in South
      Asia. Further, estimates of surgical volume suggest this region faces a critical
      shortage of surgical capacity. We aimed to estimate the total economic welfare
      losses due to the morbidity and mortality of head and neck cancer in India,
      Pakistan, and Bangladesh for 1 year (2010). METHODS: We used publicly available
      estimates from the Institute for Health Metrics and Evaluation regarding the
      morbidity and mortality of head and neck cancer in India, Pakistan, and
      Bangladesh, along with an economic concept termed the value of a statistical
      life, to estimate total economic welfare losses due to head and neck cancer in
      the aforementioned countries in the year 2010. The counterfactual scenario is
      absence of disease. Sensitivity analyses were done with regard to how the value
      of a statistical life changes with income. FINDINGS: In 2010, the most
      conservative estimate of economic welfare losses due to head and neck cancer in
      the three studied countries is US$16.9 billion (2010 USD, PPP), equivalent to
      0.26% of their combined gross domestic product (GDP). The welfare losses
      experienced by the population younger than 70 years of age accounted for US$15.2
      billion (90% of the total losses). When adjusted for the size of their respective
      economies, Bangladesh, the poorest of the three countries, incurred the greatest
      loss (US$930 million), equivalent to 0.29% of its GDP. India and Pakistan
      experienced welfare losses of US$14.1 billion and US$1.9 billion, respectively.
      These figures are equivalent to 0.26% of the GDP for both countries.
      Oropharyngeal and hypopharyngeal cancer made up the largest share of the total
      burden at 39% (US$6.6 billion), followed closely by oral cavity cancer at 34%
      (US$5.7 billion). INTERPRETATION: The burden of non-communicable diseases, to
      which cancer contributes greatly, is growing at a rapid pace in South Asia. Head
      and neck cancer is a leading cause of cancer-related mortality in this region,
      and this study suggests that the associated economic welfare losses, estimated to
      be US$16.9 billion in 2010 alone, are substantial. A number of strategies are
      available to address this burden. Surgery, as part of a multidisciplinary
      approach that includes radiation therapy and chemotherapy, plays a central part
      in the diagnosis and treatment of head and neck cancer, and building surgical
      capacity, which offers large economies of scope and scale, can not only address
      the burden of head and neck cancer, but also create a platform for beginning to
      confront the rising tide of non-communicable diseases. FUNDING: None.

PMID- 26313107
TI  - Estimation of the economic burden of injury in north India: a prospective cohort
      study.
AB  - BACKGROUND: Injuries are a serious cause of mortality and morbidity worldwide,
      with trauma being the leading cause of death in the first four decades of life.
      By contrast with the declining rates of injury seen in high-income countries, low
      income and middle-income countries (LMICs) are experiencing an increase in injury
      rates, largely due to increased motorisation in these countries. In this study,
      we report the out-of-pocket expenditure and financial risk protection from trauma
      care in a tertiary care hospital of India. METHODS: Patients who were admitted
      for at least one night in a tertiary care hospital of Chandigarh during a 1 month
      period from April 15, 2013, and May 15, 2013, were recruited. Data were collected
      for the type of injury, out-of-pocket expenditure, and mechanisms undertaken to
      cope up with the expenditure. Cases were followed up at 1 month, 2 months, and 12
      months after discharge to collect information about out-of-pocket expenditure.
      Prevalence of catastrophic expenditure-ie, if it exceeded 30% of the patient's
      annual household income-and distress financing-ie, if borrowing (with or without
      interest) or selling of assets was used to cope with high out-of-pocket
      expenditure, were assessed among patients recruited. Assuming prevalence of
      catastrophic expenditure to be 22%, with a precision of 5.5% and 5% alpha error,
      the sample size was estimated to be 218. FINDINGS: 227 patients were recruited,
      of whom 155 (68%) were followed up until 12 months. No significant differences
      were noted based on sociodemographic, injury, and hospitalisation characteristics
      between the patients who were followed up and those who were lost to follow-up.
      Average out-of-pocket expenditure per admission to hospital was US$388 (95% CI
      332-441) and at 12 months after injury was US$1046 (871-1221). Mean out-of-pocket
      expenditure for road traffic injury cases at the time of hospitalisation was
      US$400 (95% CI 344-456) and for non-road traffic injury cases was US$369 (313
      425). The prevalence of catastrophic expenditure was 30% (95% CI 26.95-33.05),
      which was significantly associated with lower income quartile (OR 23.3 [95% CI
      5.7-93.9]; p <0.01), inpatient stay greater than 7 days (OR 8.8 [95% CI 3.8
      20.6); p<0.01), major surgery (OR 4.9 [95% CI 2.2-10.8]; p<0.01), and occupation
      as wage labourers (OR 8.1 [95% CI 1.6-39.9]; p=0.01). INTERPRETATION: High
      private out-of-pocket expenditure for treatment of injury poses major economic
      burden on families. Measures aimed to increase public health spending for
      prevention of injury and to provide financial risk protection to those injured
      deserve urgent priority in India. FUNDING: The George Institute for Global
      Health, India.

PMID- 26313108
TI  - An estimate of hernia prevalence in Nepal from a countrywide community survey.
AB  - BACKGROUND: Herniorrhaphy is one of the most frequently performed general
      surgical operations worldwide; however, most low-income and middle-income
      countries (LMICs) are unable to provide this essential surgery resulting in
      substantial morbidity and mortality. This study aimed to estimate the prevalence
      of, barriers to care for, and disability from untreated hernias in Nepal.
      METHODS: A cluster randomised, cross-sectional household survey was performed in
      Nepal using the validated Surgeons OverSeas Assessment of Surgical (SOSAS) tool.
      Sample size was based on a pilot study that reported a 5% prevalence of unmet
      surgical need. 15 clusters consisting of 30 households each were sampled
      proportional to population. In each, two randomly selected family members
      underwent a verbal head-to-toe physical examination and answered questions about
      barriers to care and disability. FINDINGS: The survey sampled 1350 households,
      totalling 2695 individuals (97% response rate). 1434 (53%) of responders were men
      and 1.5% (95% CI 1.8-4.0) had a mass or swelling in the groin at time of survey.
      The age-standardised rate for inguinal hernias in men ranged from 1144 per 100
      000 persons between age 5 and 49 years and 2941 per 100 000 persons aged 50 years
      and older. 29 respondents were not able to have surgery due to lack of surgical
      services (nine; 31%), fear or mistrust of the surgical system (nine; 31%), and
      inability to afford care (six; 21%). 10 respondents (20%) were unable to work as
      previous or perform self-care due to their hernia. INTERPRETATION: Despite the
      lower than expected prevalence of inguinal hernias, more than 300 000 people in
      Nepal are currently in need of herniorrhaphy. In view that essential surgery is a
      necessary component in health systems, the prevalence of inguinal hernias and the
      cost-effectiveness of herniorrhaphy, this disease is an important target for
      LMICs planning surgical capacity improvements. FUNDING: Surgeons OverSeas,
      Association for Academic Surgery, and the Fogarty International Center.

PMID- 26313109
TI  - Burden of road traffic injuries in Nepal: results of a countrywide population
      based survey.
AB  - BACKGROUND: Road traffic injury has emerged as a leading cause of mortality,
      contributing to 2.1% of deaths globally and is predicted to be the third highest
      contributor to the global burden of mortality by 2020. This major public health
      problem disproportionately affects low-income and middle-income countries, where
      such incidents are too often underreported. Our study aims to explore the
      epidemiology of road traffic injurys in Nepal at a population level via a
      countrywide study. METHODS: The Surgeons OverSeas Assessment of Surgical Need
      (SOSAS) tool, a cluster randomised, cross-sectional nationwide survey, was
      conducted in Nepal between May 25, and June 12, 2014. Two-stage cluster sampling
      was performed: 15 of 75 districts were chosen randomly proportional to
      population; within each district, after stratification for urban and rural, and
      three clusters were randomly chosen. Questions were structured anatomically and
      designed around a representative spectrum of surgical conditions. Road traffic
      injury-related results were reported. FINDINGS: 1350 households and 2695
      individuals were surveyed with a response rate of 97%. 75 road traffic injuries
      were reported in 72 individuals (2.67% [95% CI 2.10-3.35] of the study
      population), with a mean age of 33.2 years (SD 1.85). The most commonly affected
      age group was 30-44 years, with females showing significantly lower odds of
      sustaining a road traffic injury than men (crude odds ratio 0.29 [95% CI 0.16
      0.52]). Road traffic injuries composed 19.8% of the injuries reported. Motorcycle
      crashes were the most common road traffic injuries (48.0%), followed by car,
      truck, or bus crashes (26.7%), and pedestrian or bicycle crashes (25.3%). The
      extremity was the most common anatomic site injured (74.7%). Of the 80 deaths
      reported in the previous year, 7.5% (n=6) were due to road traffic injuries.
      INTERPRETATION: This study provides the epidemiology of road traffic injuries at
      a population-based level in the first countrywide surgical needs assessment in
      Nepal. WHO reported that mortality due to road traffic injuries in Nepal in 2011
      was 1.7%, whereas our study reported 7.5%, consistent with the concept of
      underreporting of deaths in police and hospital level data noted in previous
      literature. Road traffic injuries continue to be a significant problem in Nepal,
      probably greater than previously reported; future efforts should focus on
      addressing this growing epidemic through preventive and mitigating strategies.
      FUNDING: The Association for Academic Surgery and Surgeons OverSeas.

PMID- 26313111
TI  - Epidemiology of untreated non-obstetric surgical disease in Burera District,
      Rwanda: a cross-sectional survey.
AB  - BACKGROUND: In low-income and middle-income countries, surgical epidemiology is
      largely undefined at the population level, with operative logs and hospital
      records serving as a proxy. This study assesses the distribution of surgical
      conditions that contribute the largest burden of surgical disease in Burera
      District, in northern Rwanda. We hypothesise that our results would yield higher
      rates of surgical disease than current estimates (from 2006) for similar low
      income countries, which are 295 per 100 000 people. METHODS: In March and May,
      2012, we performed a cross-sectional study in Burera District, randomly sampling
      30 villages with probability proportionate to size and randomly sampling 23
      households within the selected villages. Six Rwandan surgical postgraduates and
      physicians conducted physical examinations on all eligible participants in
      sampled households. Participants were assessed for injuries or wounds, hernias,
      hydroceles, breast mass, neck mass, obstetric fistula, undescended testes,
      hypospadias, hydrocephalus, cleft lip or palate, and club foot. Ethical approval
      was obtained from Boston Children's Hospital (Boston, MA, USA) and the Rwandan
      National Ethics Committee (Kigali, Rwanda). Informed consent was obtained from
      all participants. FINDINGS: Of the 2165 examined individuals, the overall
      prevalence of any surgical condition was 12% (95% CI 9.2-14.9) or 12 009 per 100
      000 people. Injuries or wounds accounted for 55% of the prevalence and hernias or
      hydroceles accounted for 40%, followed by neck mass (4.2%), undescended testes
      (1.9%), breast mass (1.2%), club foot (1%), hypospadias (0.6%), hydrocephalus
      (0.6%), cleft lip or palate (0%), and obstetric fistula (0%). When comparing
      study participant characteristics, no statistical difference in overall
      prevalence was noted when examining sex, wealth, education, and travel time to
      the nearest hospital. Total rates of surgically treatable disease yielded a
      statistically significant difference compared with current estimates (p<0.001).
      INTERPRETATION: Rates of surgically treatable disease are significantly higher
      than previous estimates in comparable low-income countries. The prevalence of
      surgically treatable disease is evenly distributed across demographic parameters.
      From these results, we conclude that strengthening the Rwandan health system's
      surgical capacity, particularly in rural areas, could have meaningful affect on
      the entire population. Further community-based surgical epidemiological studies
      are needed in low-income and middle-income countries to provide the best data
      available for health system planning. FUNDING: The Harvard Sheldon Traveling
      Fellowship.

PMID- 26313112
TI  - Preferable procedure for the screening of syphilis in clinical laboratories in
      China.
AB  - BACKGROUND: With the rapid expansion of infectious syphilis all over the world,
      optimal procedures for screening syphilis are urgently required. Conventional
      methods for the diagnosis of syphilis are time- and labor-consuming. We compared
      automated chemiluminescent micro-particle immunoassay (CLIA) with conventional
      methods to verify whether CLIA is feasible for syphilis screening. METHODS: A
      cross-sectional assay was conducted on 3962 serum samples tested by CLIA, rapid
      plasma reagin test (RPR), and Treponema pallidum particle agglutination (TPPA).
      Meanwhile, another 36 000 sera were screened for syphilis using CLIA and the
      positive samples were confirmed using TPPA, RPR or Western blotting. RESULTS: The
      sensitivity and specificity were 100% and 99.8% for CLIA, and 65% and 99.6% for
      RPR. With the elevation of the optical density value of samples to cut-off ratio
      (S/CO) value, the true-positive rate of CLIA increased significantly, and when
      the S/CO value exceeded 10, the true-positive rate of CLIA reached 100%. The
      false-positive rate of CLIA was 0.22%; pregnant women had the most false-positive
      results, followed by elderly people and cancer patients. CONCLUSION: CLIA is
      suggested as a screening test for the diagnosis of syphilis, while TPPA and RPR
      are required for confirming the positive samples and monitoring their activity.

PMID- 26313110
TI  - Validation of a community-based survey assessing non-obstetric surgical
      conditions in Burera District, Rwanda.
AB  - BACKGROUND: Community-based surveillance methods to monitor epidemiological
      progress in surgery have not yet been employed for surgical capacity building.
      The aim of this study was to create and assess the validity of a questionnaire
      that collected data for untreated surgically correctable diseases throughout
      Burera District, northern Rwanda, to accurately plan for surgical services.
      METHODS: A structured interview to assess for the presence or absence of ten
      index surgically treatable conditions (breast mass, cleft lip/palate, club foot,
      hernia or hydrocele [adult and paediatric]), hydrocephalus, hypospadias, injuries
      or wounds, neck mass, undescended testes, and vaginal fistula) was created. The
      interview was built based on previously validated questionnaires, forward and
      back translated into the local language and underwent focus group augmentation
      and pilot testing. In March and May, 2012, data collectors conducted the
      structured interviews with a household representative in 30 villages throughout
      Burera District, selected using a two-stage cluster sampling design. Rwandan
      physicians revisited the surveyed households to perform physical examinations on
      all household members, used as the gold standard to validate the structured
      interview. Ethical approval was obtained from Boston Children's Hospital (Boston,
      MA, USA) and the Rwandan National Ethics Committee (Kigali, Rwanda). Informed
      consent was obtained from all households. FINDINGS: 2990 individuals were
      surveyed, a 97% response rate. 2094 (70%) individuals were available for physical
      examination. The calculated overall sensitivity of the structured interview tool
      was 44.5% (95% CI 38.9-50.2) and the specificity was 97.7% (96.9-98.3%;
      appendix). The positive predictive value was 70% (95% CI 60.5-73.5), whereas the
      negative predictive value was 91.3% (90.0-92.5). The conditions with the highest
      sensitivity and specificity, respectively, were hydrocephalus (100% and 100%),
      clubfoot (100% and 99.8%), injuries or wounds (54.7% and 98.9%), and hypospadias
      (50% and 100%). Injuries or wounds and hernias or hydroceles were the conditions
      most frequently identified on examination that were not reported during the
      interview (appendix). INTERPRETATION: To the best of our knowledge, this study
      provides the first attempt to validate a community-based surgical surveillance
      tool. The finding of low sensitivity limits the use of the tool, which will
      require further revision, and calls into question previously published
      unvalidated community surgical survey data. To improve validation of community
      based surveys, community education efforts on common surgically treatable
      conditions are needed in conjunction with increased access to surgical care.
      Accurate community-based surveys are crucial to integrated health system planning
      that includes surgical care as a core component. FUNDING: The Harvard Sheldon
      Traveling Fellowship.

PMID- 26313113
TI  - Practical and conceptual issues of clinical trial registration for Brazilian
      researchers.
AB  - CONTEXT AND OBJECTIVE: Clinical trial registration is a prerequisite for
      publication in respected scientific journals. Recent Brazilian regulations also
      require registration of some clinical trials in the Brazilian Clinical Trials
      Registry (ReBEC) but there is little information available about practical issues
      involved in the registration process. This article discusses the importance of
      clinical trial registration and the practical issues involved in this process.
      DESIGN AND SETTING: Descriptive study conducted by researchers within a
      postgraduate program at a public university in Sao Paulo, Brazil. METHODS:
      Information was obtained from clinical trial registry platforms, article
      reference lists and websites (last search: September 2014) on the following
      topics: definition of a clinical trial, history, purpose and importance of
      registry platforms, the information that should be registered and the
      registration process. RESULTS: Clinical trial registration aims to avoid
      publication bias and is required by Brazilian journals indexed in LILACS and
      SciELO and by journals affiliated to the International Committee of Medical
      Journal Editors (ICMJE). Recent Brazilian regulations require that all clinical
      trials (phases I to IV) involving new drugs to be marketed in this country must
      be registered in ReBEC. The pros and cons of using different clinical trial
      registration platforms are discussed. CONCLUSIONS: Clinical trial registration is
      important and various mechanisms to enforce its implementation now exist.
      Researchers should take into account national regulations and publication
      requirements when choosing the platform on which they will register their trial.

PMID- 26313116
TI  - Retractions in general and internal medicine in a high-profile scientific
      indexing database.
AB  - CONTEXT AND OBJECTIVE: Increased frequency of retractions has recently been
      observed, and retractions are important events that deserve scientific
      investigation. This study aimed to characterize cases of retraction within
      general and internal medicine in a high-profile database, with interest in the
      country of origin of the article and the impact factor (IF) of the journal in
      which the retraction was made. DESIGN AND SETTING: This study consisted of
      reviewing retraction notes in the Thomson-Reuters Web of Knowledge (WoK) indexing
      database, within general and internal medicine. METHODS: The retractions were
      classified as plagiarism/duplication, error, fraud and authorship problems and
      then aggregated into two categories: "plagiarism/duplication" and "others." The
      countries of origin of the articles were dichotomized according to the median of
      the indicator "citations per paper" (CPP), and the IF was dichotomized according
      to its median within general and internal medicine, also obtained from the WoK
      database. These variables were analyzed using contingency tables according to CPP
      (high versus low), IF (high versus low) and period (1992-2002 versus 2003-2014).
      The relative risk (RR) and 95% confidence interval (CI) were estimated for
      plagiarism/duplication. RESULTS: A total of 86 retraction notes were identified,
      and retraction reasons were found for 80 of them. The probability that
      plagiarism/duplication was the reason for retraction was more than three times
      higher for the low CPP group (RR: 3.4; 95% CI: [1.9-6.2]), and similar results
      were seen for the IF analysis. CONCLUSION: The study identified greater incidence
      of plagiarism/duplication among retractions from countries with lower scientific
      impact.

PMID- 26313117
TI  - Diversity of the Genetic Environment of the blaKPC-2 Gene Among Klebsiella
      pneumoniae Clinical Isolates in a Chinese Hospital.
AB  - KPC-producing Klebsiella pneumoniae (KPC-Kp) has been frequently reported
      worldwide and constitutes a major healthcare threat, given their extensively drug
      resistant phenotypes. In this study, we report the characterization of the
      genetic environment of blaKPC-2 gene in KPC-Kp clinical strains from China
      belonging to diverse genotypes. Thirty-five nonduplicated KPC-Kp isolates
      collected in a Chinese hospital during 2012 were analyzed. All were multidrug
      resistant due to the presence of other resistance determinants, including metallo
      beta-lactamases (IMP-4, NDM-1), extended-spectrum beta-lactamases (CTX-M-14, -15,
      -3, -10, and SHV-12), 16S rRNA methylases (armA and rmtB), and plasmid-mediated
      quinolone resistance determinants [qnrA, B, S, aac(6')-Ib-cr]. Using pulsed-field
      gel electrophoresis (PFGE), the 35 isolates were grouped into 12 clusters that
      were further identified as 15 sequence types (STs) by multilocus sequence typing.
      ST11 K. pneumoniae was the predominant clone attributed to the outbreak. blaKPC-2
      was carried in plasmids of various sizes and incompatibility types. The genetic
      environment analysis, based on genetic structure in the plasmid pKP048, revealed
      five distinct platforms: the most prevalent structure was the continual
      occurrence in diverse STs (ST11, ST258, ST340, ST395, ST437, and ST494),
      harboring plasmid of blaKPC-2 in a genetic environment flanked by ISKpn8 and
      ISKpn6 like. This study highlights the continued evolution of the genetic
      environment of the blaKPC-2 gene in our hospital and movement to multiple plasmid
      backbones that results in acquisition by multiple clones of K. pneumoniae. 

PMID- 26313120
TI  - Better big data.
AB  - By 2018, Medicare payments will be tied to quality of care. The Centers for
      Medicare and Medicaid Services currently use quality-based metric for some
      reimbursements through their different programs. Existing and future quality
      metrics will rely on risk adjustment to avoid unfairly punishing those who see
      the sickest, highest-risk patients. Despite the limitations of the data used for
      risk adjustment, there are potential solutions to improve the accuracy of these
      codes by calibrating data by merging databases and compiling information
      collected for multiple reporting programs to improve accuracy. In addition,
      healthcare staff should be informed about the importance of risk adjustment for
      quality of care assessment and reimbursement. As the number of encounters tied to
      value-based reimbursements increases in inpatient and outpatient care, coupled
      with accurate data collection and utilization, the methods used for risk
      adjustment could be expanded to better account for differences in the care
      delivered in diverse settings. 

PMID- 26313119
TI  - Wrapping of intracranial aneurysms: Single-center series and systematic review of
      the literature.
AB  - BACKGROUND: Circumferential wrapping of the aneurysm wall with a variety of
      materials is a well-known therapeutic approach for the repair of unclippable
      intracranial aneurysms (IAs). Wrapping materials can stimulate foreign-body
      inflammatory reactions and parent artery narrowing with resultant ischemic
      stroke. In this study, a single-center retrospective review of the outcome with
      wrapping of IAs is presented beside an analysis of existing literature. METHODS:
      For the institutional analysis, all patients who underwent wrapping of IAs in the
      last five years were analyzed. For the analysis of the literature, a MEDLINE
      search between 1990 and the present was performed for clinical series reporting
      wrapping of IAs. Specifically, the risk of rebleeding, cerebrovascular
      complications, and the incidence of granuloma formation were evaluated. RESULTS:
      Two hundred and ninety patients with IA were surgically treated in our
      department. Fifteen patients (5.2%) underwent wrapping of IA. Early parent artery
      narrowing occurred in one patient (6.7%) and was associated with ischemic stroke.
      Delayed cerebrovascular complications, including parent artery narrowing (one
      case), granuloma formation (one case), and fatal bleeding from an unruptured
      aneurysm, occurred in three patients (20%). For the review of the literature, 197
      cases of wrapped aneurysms were collected. Bleeding after wrapping occurred in 16
      (12%) of the patients with ruptured aneurysms. Acute ischemic complications were
      reported in 7 cases (3.5%) and granuloma formation was observed in 3 patients
      (1.5%). CONCLUSIONS: These data suggest that the microsurgical wrapping of IAs
      present a risk of ischemic complications and granuloma formation. Additionally,
      the rebleeding rate of ruptured aneurysms remains high, although still lower than
      the natural history of untreated ruptured aneurysms.

PMID- 26313121
TI  - Ustekinumab as a therapeutic option for Takayasu arteritis: from genetic findings
      to clinical application.

PMID- 26313122
TI  - Rice alpha-fucosidase active against plant complex type N-glycans containing
      Lewis a epitope: purification and characterization.
AB  - Rice alpha-fucosidase (alpha-fucosidase Os, 58 kDa) that is active for alpha1-4
      fucosyl linkage in Lewis a unit of plant N-glycans was purified to homogeneity.
      alpha-fucosidase Os showed activity against alpha1-3 fucosyl linkage in Lacto-N
      fucopentaose III but not alpha1-3 fucosyl linkage in the core of plant N-glycans.
      The N-terminal sequence of alpha-fucosidase Os was identified as A-A-P-T-P-P-P-L
      , and this sequence was found in the amino acid sequence of the putative rice
      alpha-fucosidase 1 (Os04g0560400). 

PMID- 26313123
TI  - Flexible receptor docking for drug discovery.
AB  - INTRODUCTION: Molecular docking has become a popular method for virtual
      screening. Docking small molecules to a rigid biological receptor is fast but
      could produce many false negatives and identify less diverse compounds. Flexible
      receptor docking has alleviated this problem. AREAS COVERED: This article focuses
      on reviewing ensemble docking as an approximate but inexpensive method to
      incorporate receptor flexibility in molecular docking. It outlines key features
      and recent advances of this method and points out problem areas that need to be
      addressed to make it even more useful in drug discovery. EXPERT OPINION: Among
      the different methods introduced for flexible receptor docking, ensemble docking
      represents one of the most popular approaches, especially for high-throughput
      virtual screening. One can generate structural ensembles by using experimental
      structures, by structural modeling and by various types of molecular simulations.
      In building a structural ensemble, a judicious choice of the structures to be
      included can improve performance. Furthermore, reducing the size of the
      structural ensemble can cut computational costs, and removing the structures that
      can bind few ligands well could enrich the number of true actives identified by
      ensemble docking. The ability of ensemble docking to identify more true positives
      at the top of a rank-ordered list also depends on the choice of the methods to
      score and rank compounds, an area that needs further research.

PMID- 26313124
TI  - The influence of asthma control on psychosocial outcomes for pregnant women with
      asthma.
AB  - OBJECTIVE: To investigate the relationship between asthma control and
      psychosocial outcomes in pregnant women with asthma. METHODS: Secondary analysis
      (N = 221) of a randomized controlled trial of treatment adjustments, based on
      fractional exhaled nitric oxide versus clinical guideline-based algorithms.
      Psychosocial variables included generic and asthma-specific quality of life
      (SF12, AQLQ-M), illness perceptions (BIPQ), perceived control (PCAQ), perceived
      risk of side effects (PRSE) and anxiety (STAI-6). Asthma control was defined as
      controlled (Asthma Control Questionnaire (ACQ7) <=1.5 at randomization and end of
      study), improved (ACQ7 > 1.5 at randomization and <=1.5 at end of study) and
      unimproved (ACQ7 >1.5 at end of study). Regression models were fitted for each
      psychosocial measure at the end of the study, with adjustment for baseline values
      and smoking status, with predictor variable asthma control. RESULTS: Women with
      unimproved asthma had poorer physical (SF12, p = 0.012) and asthma-specific
      quality of life across all domains (AQLQ-M, p <= 0.012) compared to women with
      controlled asthma. They believed that they had less control over their asthma
      (PCAQ total p = 0.014), had more symptoms and that their illness had a greater
      effect on their emotions and their lives in general (BIPQ identity, consequences,
      concern, emotional response p <= 0.015). Women with improved asthma control had
      significantly lower AQLQ-M breathlessness (p = 0.048) and lower total scores (p =
      0.04) than women with controlled asthma. CONCLUSIONS: Pregnant women who are not
      able to get control of their asthma symptoms may experience worse quality of life
      and are likely to have more negative perceptions about their condition.

PMID- 26313125
TI  - The cell ratchet: interplay between efficient protrusions and adhesion determines
      cell motion.
AB  - Many physiological and pathological processes involve directed cell motion. In
      general, migrating cells are represented with a polarized morphology with
      extending and retracting protrusions at the leading edge. However, cell motion is
      a more complex phenomenon. Cells show heterogeneous morphologies and high
      protrusive dynamics is not always related to cell shape. This prevents the
      quantitative prediction of cell motion and the identification of cellular
      mechanisms setting directionality. Here we discuss the importance of protrusion
      fluctuations in directed cell motion. We show how their spatiotemporal
      distribution and dynamics determine the fluctuations and directions of cell
      motion for NIH3T3 fibroblasts plated on micro-patterned adhesive ratchets. (1) We
      introduce efficient protrusions and direction index which capture short-term cell
      motility over hours: these new read-outs allow the prediction of parameters
      characteristic for the long-term motion of cells over days. The results may have
      important implications for the study of biological phenomena where directed cell
      migration is involved, in morphogenesis and in cancer. 

PMID- 26313126
TI  - Structural, optical and photoelectrochemical characterizations of monoclinic
      Ta3N5 thin films.
AB  - Monoclinic Ta3N5 thin films were synthesized by thermal nitridation of amorphous
      Ta2O5 films directly sputtered by radio frequency magnetron sputtering. The
      samples were studied by high resolution transmission electron microscopy, X-ray
      photoelectron spectroscopy, UV-Vis-NIR spectrophotometry, rietveld refinements,
      spectroscopic ellipsometry and electrochemical techniques. The surface
      composition of Ta3N5 thin film was found to be different than the underlying
      film, affecting the optical properties of the material. Rietveld refinement has
      confirmed that the nitridation process results in Schottky and oxygen
      substitutional defects within the crystalline structure of monoclinic Ta3N5 thin
      film. The optical constants of the film were obtained by spectroscopic
      ellipsometry within a spectral range of 4.60-0.54 eV, i.e. 270-2300 nm. The
      suitable parameterization was found to consist of three Tauc-Lorentz and one
      Lorentz oscillators. The conduction band, valence band and the flat band
      positions were determined by photoelectrochemical techniques, presenting a strong
      dependence on pH of the eletrolyte. Improved photocurrent was obtained in
      alkaline conditions and attributed to the shorter depletion region width measured
      by Mott-Schottky and the lower recombination life time measured by open circuit
      potential decay analyses. 

PMID- 26313127
TI  - Consequences of using different soil texture determination methodologies for soil
      physical quality and unsaturated zone time lag estimates.
AB  - Elucidation of when the loss of pollutants, below the rooting zone in
      agricultural landscapes, affects water quality is important when assessing the
      efficacy of mitigation measures. Investigation of this inherent time lag (t(T))
      is divided into unsaturated (t(u)) and saturated (t(s)) components. The duration
      of these components relative to each other differs depending on soil
      characteristics and the landscape position. The present field study focuses on tu
      estimation in a scenario where the saturated zone is likely to constitute a
      higher proportion of t(T). In such instances, or where only initial breakthrough
      (IBT) or centre of mass (COM) is of interest, utilisation of site and depth
      specific "simple" textural class or actual sand-silt-clay percentages to generate
      soil water characteristic curves with associated soil hydraulic parameters is
      acceptable. With the same data it is also possible to estimate a soil physical
      quality (S) parameter for each soil layer which can be used to infer many other
      physical, chemical and biological quality indicators. In this study, hand
      texturing in the field was used to determine textural classes of a soil profile.
      Laboratory methods, including hydrometer, pipette and laser diffraction methods
      were used to determine actual sand-silt-clay percentages of sections of the same
      soil profile. Results showed that in terms of S, hand texturing resulted in a
      lower index value (inferring a degraded soil) than that of pipette, hydrometer
      and laser equivalents. There was no difference between S index values determined
      using the pipette, hydrometer and laser diffraction methods. The difference
      between the three laboratory methods on both the IBT and COM stages of t(u) were
      negligible, and in this instance were unlikely to affect either groundwater
      monitoring decisions, or to be of consequence from a policy perspective. When
      t(u) estimates are made over the full depth of the vadose zone, which may extend
      to several metres, errors resulting from the use of hydraulic parameters
      generated from hand texture data will be resultantly greater, and may lead to
      flawed predictions regarding the achievability of water policy targets. For this
      reason laboratory analysis, regardless of method, should be preferred to simple
      field assessments.

PMID- 26313128
TI  - Morphological alteration, lysosomal membrane fragility and apoptosis of the cells
      of Indian freshwater sponge exposed to washing soda (sodium carbonate).
AB  - Washing soda is chemically known as sodium carbonate and is a component of
      laundry detergent. Domestic effluent, drain water and various anthropogenic
      activities have been identified as major routes of sodium carbonate contamination
      of the freshwater ecosystem. The freshwater sponge, Eunapius carteri, bears
      ecological and evolutionary significance and is considered as a bioresource in
      aquatic ecosystems. The present study involves estimation of morphological
      damage, lysosomal membrane integrity, activity of phosphatases and apoptosis in
      the cells of E. carteri under the environmentally realistic concentrations of
      washing soda. Exposure to washing soda resulted in severe morphological
      alterations and damages in cells of E. carteri. Fragility and destabilization of
      lysosomal membranes of E. carteri under the sublethal exposure was indicative to
      toxin induced physiological stress in sponge. Prolonged exposure to sodium
      carbonate resulted a reduction in the activity of acid and alkaline phosphatases
      in the cells of E. carteri. Experimental concentration of 8 mg/l of washing soda
      for 192 h yielded an increase in the physiological level of cellular apoptosis
      among the semigranulocytes and granulocytes of E. carteri, which was suggestive
      to possible shift in apoptosis mediated immunoprotection. The results were
      indicative of an undesirable shift in the immune status of sponge. Contamination
      of the freshwater aquifers by washing soda thus poses an alarming
      ecotoxicological threat to sponges.

PMID- 26313129
TI  - The effects of cognitive intervention on cognitive impairments after intensive
      care unit admission.
AB  - Patients who survive critical illness commonly suffer cognitive impairments. We
      aimed to study the effects of cognitive intervention to treat the long-term
      impairments observed among different populations of intensive care unit (ICU)
      survivors. The results showed that the intervention significantly suppressed the
      deterioration of cognitive function in these patients. Medical and neurological
      ICU survivors were more susceptible than post-anaesthesia ICU patients to severe
      cognitive damage. In the former, the deterioration of impairments can be slowed
      by cognitive intervention. In comparison, intervention exerted significantly
      positive effects on the recovery of the cognitive functions of post-anaesthesia
      care unit patients. Furthermore, young populations were more likely than older
      populations to recover from acute cognitive impairments, and the impairment
      observed among the older population seemed to be multi-factorial and
      irreversible.

PMID- 26313130
TI  - MhNCED3 in Malus hupehensis Rehd. induces NO generation under osmotic stress by
      regulating ABA accumulation.
AB  - Abscisic acid (ABA) biosynthesis has been widely characterized in plants, whereas
      the effects of ABA biosynthesis on nitric oxide (NO) generation in osmotic stress
      are less well understood. In this study, Malus hupehensis Rehd. 9-cis
      epoxycarotenoid dioxygenase gene (MhNCED3) which is the key gene in ABA
      biosynthesis was transformed into wild type (WT) and 129B08/nced3 mutant (AtNCED3
      deficient), respectively, and two transgenic Arabidopsis lines were obtained. The
      transgenic Arabidopsis lines displayed higher endogenous ABA content, NO
      generation rate, AtNIA1 transcript level and nitrate reductase (NR) activity than
      WT and 129B08/nced3 mutant. Ectopic expression of MhNCED3 reduced the electrolyte
      leakage and relieved Arabidopsis damage caused by 20% PEG on the growth and
      development. The ABA content, NO generation rate, AtNIA1 expression and NR
      activity increased after 20% PEG treatment, importantly, their increases
      amplitude relative to that in control were higher in two transgenic lines.
      Additionally, during the treatment for the four genotype Arabidopsis, the time of
      ABA contents reaching the highest peak was earlier than the time of NO
      generation, AtNIA1 expression and NR activity reaching their highest peak. These
      results show that NCED gene indirectly induced endogenous NO generation in
      osmotic-stressed Arabidopsis partially contributing to the up-regulation of
      AtNIA1 expression and NR activity. 

PMID- 26313131
TI  - Simultaneous quantitation of quetiapine and its active metabolite norquetiapine
      in rat plasma and brain tissue by high performance liquid
      chromatography/electrospray ionization tandem mass spectrometry (LC-MS/MS).
AB  - A sensitive method to simultaneously quantitate quetiapine and norquetiapine in
      rat plasma and brain tissue was developed using a one-step liquid-liquid
      extraction for sample preparation and LC-MS/MS for detection. The method provided
      a linear range of 1.0-500.0ng/mL for each analyte in plasma and 3.0-1500.0ng/g in
      brain tissue. The method was validated with precision within 15% relative
      standard deviation (RSD), accuracy within 15% relative error (RE), matrix effects
      within 10% and a consistent recovery. This method has been successfully applied
      in a preclinical study of quetiapine and norquetiapine to simultaneously
      determine their concentrations in rat plasma and brain tissue. 

PMID- 26313132
TI  - Variation of the Electrophilicity Index along the Reaction Path.
AB  - Some exact conditions for the extremals of the electrophilicity index, omega =
      MU(2)/2eta (Parr, R. G.; von Szentpaly, L.; Liu, S. J. Am. Chem. Soc. 1999, 121,
      1922), along an arbitrary reaction coordinate, have been carefully examined.
      Implications within the widely used finite difference approximation for the
      density-functional based reactivity descriptors, their relationship with the
      maximum hardness principle, and the reliability of the general relationships have
      been tested in the framework of computational evidence for some simple systems of
      chemical interest. 

PMID- 26313133
TI  - BDNF methylation and depressive disorder in acute coronary syndrome: The K-DEPACS
      and EsDEPACS studies.
AB  - OBJECTIVE: Epigenetic regulation investigated by methylation tests has been
      associated with pathogenesis and treatment response in depressive disorders.
      However, these hypotheses have rarely been tested in patients with acute coronary
      syndrome (ACS) vulnerable to depression. This study aimed to investigate whether
      brain derived neurotrophic factor (BDNF) methylation status is associated with
      occurrence and treatment response of depressive disorder in ACS. METHODS: Of 969
      patients with recently developed ACS were recruited at baseline, 711 were
      followed 1 year thereafter. Depressive disorder was diagnosed according to DSM-IV
      criteria, and classified as baseline prevalent, and follow-up incident or
      persistent depressive disorder according to status at the two examinations. In
      addition, of 378 baseline participants with depressive disorder, 255 were
      randomized to a 24-week double blind trial of escitalopram (N=127) or placebo
      (N=128), while the remaining 123 received conventional medical treatment for ACS.
      BDNF methylation percentages were estimated using leukocyte DNA, and a range of
      demographic and clinical characteristics were evaluated as covariates. RESULTS:
      In logistic regression models, higher BDNF methylation status was independently
      associated with prevalent depressive disorder at baseline and with its
      persistence at follow-up. Escitalopram was more effective than placebo for
      treating depressive disorder in those with a higher methylation, and this effects
      lead to prevent persistent depressive disorder. CONCLUSIONS: ACS patients with
      higher BDNF methylation were susceptible to early depressive disorder, and to its
      persistence one year later. Adequate antidepressants treatment may effective
      particularly in those with higher BDNF methylation and then can overcome
      epigenetic vulnerability for depression persistence in ACS patients.
      ClinicalTrial.gov identifier for the 24 week drug trial, NCT00419471.

PMID- 26313135
TI  - Nitric Oxide Reduction by Carbon Monoxide over Supported Hexaruthenium Cluster
      Catalysts. 1. The Active Site Structure That Depends on Supporting Metal Oxide
      and Catalytic Reaction Conditions.
AB  - Ruthenium site structures supported on metal oxide surfaces were designed by
      reacting organometallic Ru cluster [Ru6C(CO)16](2-) or [Ru6(CO)18](2-) with
      various metal oxides, TiO2, Al2O3, MgO, and SiO2. The surface Ru site structure,
      formed under various catalyst preparation and reaction conditions, was
      investigated by the Ru K-edge extended X-ray absorption fine structure (EXAFS).
      Samples of [Ru6C(CO)16](2-)/TiO2(anatase) and [Ru6C(CO)16](2-)/TiO2(rutile) were
      found to retain the original Ru6C framework when heated in the presence of NO
      (2.0 kPa) or NO (2.0 kPa) + CO (2.0 kPa) at 423 K, i.e., catalytic reaction
      conditions for NO decomposition. At 523 K, the Ru-Ru bonds of the Ru6C framework
      were cleaved by the attack of NO. In contrast, the Ru site became spontaneously
      dispersed over TiO2 (anatase). When being supported over TiO2 (mesoporous), MgO,
      or Al2O3, the Ru6C framework split into fragments in gaseous NO or NO + CO even
      at 423 K. The Ru6 framework of [Ru6(CO)18](2-) was found to break easily into
      smaller ensembles in the presence of NO and/or CO at 423 K on support. Taking
      into consideration the realistic environments in which these catalysts will be
      used, we also examined the effect of water and oxygen. When water was introduced
      to the sample [Ru6C(CO)16](2-)/TiO2(anatase) at 423 K, it did not have any
      effects on the stabilized Ru6C framework structure. In the presence of oxygen
      gas, however, the Ru hexanuclear structure decomposed into isolated Ru cations
      bound to surface oxygen atoms of TiO2 (anatase). 

PMID- 26313134
TI  - Evidence of an IFN-gamma by early life stress interaction in the regulation of
      amygdala reactivity to emotional stimuli.
AB  - INTRODUCTION: Since numerous studies have found that exposure to early life
      stress leads to increased peripheral inflammation and psychiatric disease, it is
      thought that peripheral immune activation precedes and possibly mediates the
      onset of stress-associated psychiatric disease. Despite early studies, IFNgamma
      has received little attention relative to other inflammatory cytokines in the
      context of the pathophysiology of affective disorders. Neuroimaging
      endophenotypes have emerged recently as a promising means of elucidating these
      types of complex relationships including the modeling of the interaction between
      environmental factors and genetic predisposition. Here we investigate the GxE
      relationship between early-life stress and genetic variants of IFNgamma on
      emotion processing. METHODS: To investigate the impact of the relationship
      between genetic variants of IFNgamma (rs1861494, rs2069718, rs2430561) and early
      life stress on emotion processing, a sample of healthy adults (n=409) undergoing
      an emotional faces paradigm in an fMRI study were genotyped and analysed.
      Information on early life stress was obtained via Childhood Trauma Questionnaire
      (CTQ). RESULTS: A positive association between early life stress and amygdala
      reactivity was found. Specifically, the main effect of genotype of rs1861494 on
      amygdala reactivity indicates a higher neural response in C allele carriers
      compared to T homozygotes, while we did not find main effects of rs2069718 and
      rs2430561. Importantly, interaction analyses revealed a specific interaction
      between IFNgamma genotype (rs1861494) and early life stress affecting amygdala
      reactivity to emotional faces, resulting from a positive association between CTQ
      scores and amygdala reactivity in C allele carriers while this association was
      absent in T homozygotes. CONCLUSIONS: Our findings indicate that firstly the
      genetic variant of IFNgamma (rs1861494) is involved with the regulation of
      amygdala reactivity to emotional stimuli and secondly, that this genetic variant
      moderates effects of early life stress on emotion processing. These findings
      reiterate the importance that inflammatory genes play in the interaction with
      early life stress and the regulation of emotion processing.

PMID- 26313136
TI  - Novel C,N-Cyclometalated Benzimidazole Ruthenium(II) and Iridium(III) Complexes
      as Antitumor and Antiangiogenic Agents: A Structure-Activity Relationship Study.
AB  - A series of novel C,N-cyclometalated benzimidazole ruthenium(II) and iridium(III)
      complexes of the types [(eta(6)-p-cymene)RuCl(kappa(2)-N,C-L)] and [(eta(5)
      C5Me5)IrCl(kappa(2)-N,C-L)] (HL = methyl 1-butyl-2-arylbenzimidazolecarboxylate)
      with varying substituents (H, Me, F, CF3, MeO, NO2, and Ph) in the R4 position of
      the phenyl ring of 2-phenylbenzimidazole chelating ligand of the ruthenium (3a-g)
      and iridium complexes (4a-g) have been prepared. The cytotoxic activity of the
      new ruthenium(II) and iridium(III) compounds has been evaluated in a panel of
      cell lines (A2780, A2780cisR, A427, 5637, LCLC, SISO, and HT29) in order to
      investigate structure-activity relationships. Phenyl substitution at the R4
      position shows increased potency in both Ru and Ir complexes (3g and 4g,
      respectively) as compared to their parent compounds (3a and 4a) in all cell
      lines. In general, ruthenium complexes are more active than the corresponding
      iridium complexes. The new ruthenium and iridium compounds increased caspase-3
      activity in A2780 cells, as shown for 3a,d and 4a,d. Compound 4g is able to
      increase the production of ROS in A2780 cells. Furthermore, all the new compounds
      are able to overcome the cisplatin resistance in A2780cisR cells. In addition,
      some of the metal complexes effectively inhibit angiogenesis in the human
      umbilical vein endothelial cell line EA.hy926 at 0.5 MUM, the ruthenium
      derivatives 3g (Ph) and 3d (CF3) being the best performers. QC calculations
      performed on some ruthenium model complexes showed only moderate or slight
      electron depletion at the phenyl ring of the C,N-cyclometalated ligand and the
      chlorine atom on increasing the electron withdrawing effect of the R substituent.

PMID- 26313137
TI  - E-DNA sensor of Mycobacterium tuberculosis based on electrochemical assembly of
      nanomaterials (MWCNTs/PPy/PAMAM).
AB  - Two-step electrochemical patterning methods have been employed to elaborate
      composite nanomaterials formed with multiwalled carbon nanotubes (MWCNTs) coated
      with polypyrrole (PPy) and redox PAMAM dendrimers. The nanomaterial has been
      demonstrated as a molecular transducer for electrochemical DNA detection. The
      nanocomposite MWCNTs-PPy has been formed by wrapping the PPy film on MWCNTs
      during electrochemical polymerization of pyrrole on the gold electrode. The
      MWCNTs-PPy layer was modified with PAMAM dendrimers of fourth generation (PAMAM
      G4) with covalent bonding by electro-oxidation method. Ferrocenyl groups were
      then attached to the surface as a redox marker. The electrochemical properties of
      the nanomaterial (MWCNTs-PPy-PAMAM-Fc) were studied using both square wave
      voltammetry and cyclic voltammetry to demonstrate efficient electron transfer.
      The nanomaterial shows high performance in the electrochemical detection of DNA
      hybridization leading to a variation in the electrochemical signal of ferrocene
      with a detection limit of 0.3 fM. Furthermore, the biosensor demonstrates ability
      for sensing DNA of rpoB gene of Mycobacterium tuberculosis in real PCR samples.
      Developed biosensor was suitable for detection of sequences with a single
      nucleotide polymorphism (SNP) T (TCG/TTG), responsible for resistance of M.
      tuberculosis to rifampicin drug, and discriminating them from wild-type samples
      without such mutation. This shows potential of such systems for further
      application in pathogens diagnostic and therapeutic purpose. 

PMID- 26313139
TI  - Biological significance of miR-126 expression in atrial fibrillation and heart
      failure.
AB  - We investigated the biological significance of microRNA-126 (miR-126) expression
      in patients with atrial fibrillation (AF) and/or heart failure (HF) to examine
      the possible mechanism of miR-126-dependent AF and development of HF. A total of
      103 patients were divided into three groups: AF group (18 men and 17 women, mean
      age: 65.62+/-12.72 years), HF group (17 men and 15 women, mean age: 63.95+/-19.71
      years), and HF-AF group (20 men and 16 women, mean age: 66.56+/-14.37 years).
      Quantitative real-time PCR was used to measure relative miR-126 expression as
      calculated by the 2-DeltaDeltaCt method. miR-126 was frequently downregulated in
      the 3 patient groups compared with controls. This reduction was significantly
      lower in permanent and persistent AF patients than in those with paroxysmal AF
      (P<0.05, t-test). Moreover, miR-126 expression was markedly lower in the HF-AF
      group compared with the AF and HF groups. The 3 patient groups had higher N
      terminal prohormone brain natriuretic peptide (NT-proBNP) levels, lower left
      ventricular ejection fraction (LVEF), larger left atrial diameter, and higher
      cardiothoracic ratio compared with controls. There were significant differences
      in NT-proBNP levels and LVEF among the AF, HF, and HF-AF groups. Pearson
      correlation analysis showed that relative miR-126 expression was positively
      associated with LVEF, logarithm of NT-proBNP, left atrial diameter,
      cardiothoracic ratio, and age in HF-AF patients. Multiple linear regression
      analysis showed that miR-126 expression was positively correlated with LVEF, but
      negatively correlated with the logarithm of NT-pro BNP and the cardiothoracic
      ratio (all P<0.05). Serum miR-126 levels could serve as a potential candidate
      biomarker for evaluating the severity of AF and HF. However, to confirm these
      results, future studies with a larger and diverse patient population are
      necessary. 

PMID- 26313140
TI  - Development and applications of the SWAN rating scale for assessment of attention
      deficit hyperactivity disorder: a literature review.
AB  - This study reviewed the use of the Strengths and Weaknesses of Attention
      Deficit/Hyperactivity-symptoms and Normal-behaviors (SWAN) rating scale in
      diagnostic and evolutive approaches to attention deficit hyperactivity disorder
      (ADHD) and in correlational studies of the disorder. A review of articles
      published in indexed journals from electronic databases was conducted and 61
      articles on the SWAN scale were analyzed. From these, 27 were selected to a)
      examine use of SWAN in research on attention disorders and b) verify evidence of
      its usefulness in the areas of genetics, neuropsychology, diagnostics,
      psychiatric comorbidities, neuroimaging, pharmacotherapy, and to examine its
      statistical reliability and validity in studies of diverse populations. This
      review of articles indicated a growing use of the SWAN scale for diagnostic
      purposes, for therapy, and in research on areas other than ADHD, especially when
      compared with other reliable scales. Use of the scale in ADHD diagnosis requires
      further statistical testing to define its psychometric properties. 

PMID- 26313141
TI  - Probing the mechanism of plasma protein adsorption on Au and Ag nanoparticles
      with FT-IR spectroscopy.
AB  - Protein-nanoparticle interactions are important in biomedical applications of
      nanoparticles and for growing biosafety concerns about nanomaterials. In this
      study, the interactions of four plasma proteins, human serum albumin (HSA),
      myoglobin (MB), hemoglobin (HB), and trypsin (TRP), with Au and Ag nanoparticles
      were investigated by FT-IR spectroscopy. The secondary structure of thio-proteins
      changed with time during incubation with Au and Ag nanoparticles, but the
      secondary structures of non-thio-proteins remained unchanged. The incubation time
      for structural changes depended on the sulfur-metal bond energy; the stronger the
      sulfur-metal energy, the less the time needed. H/D exchange experiments revealed
      that protein-NP complexes with thio-proteins were less dynamic than free
      proteins. No measurable dynamic differences were found between free non-thio
      proteins and the protein-Au (or Ag) nanoparticle complex. Therefore, the impact
      of covalent bonds on the protein structure is greater than that of the
      electrostatic force. 

PMID- 26313142
TI  - A probe with aggregation induced emission characteristics for screening of
      iodide.
AB  - The dilution controlled aggregation enhanced emission of spherically aggregated
      form of a triazole based probe dies down upon detecting iodide over other
      inorganic anions. The sensing is realised as a dynamic quenching mechanism
      dominated event. Being highly selective for iodide, the probe finds application
      in the detection of iodide in human urine. 

PMID- 26313143
TI  - Bioreactor-Based Online Recovery of Human Progenitor Cells with Uncompromised
      Regenerative Potential: A Bone Tissue Engineering Perspective.
AB  - The use of a 3D perfusion culture environment for stem cell expansion has been
      shown to be beneficial for maintenance of the original cell functionality but due
      to several system inherent characteristics such as the presence of extracellular
      matrix, the continued development and implementation of 3D perfusion bioreactor
      technologies is hampered. Therefore, this study developed a methodology for
      harvesting a progenitor cell population from a 3D open porous culture surface
      after expansion in a perfusion bioreactor and performed a functional
      characterization of the expanded cells. An initial screening showed collagenase
      to be the most interesting reagent to release the cells from the 3D culture
      surface as it resulted in high yields without compromising cell viability.
      Subsequently a Design of Experiment approach was used to obtain optimized 3D
      harvest conditions by assessing the interplay of flow rate, collagenase
      concentration and incubation time on the harvest efficiency, viability and single
      cell fraction. Cells that were recovered with the optimized harvest protocol, by
      perfusing a 880 U/ml collagenase solution for 7 hours at a flow rate of 4 ml/min,
      were thereafter functionally analyzed for their characteristics as expanded
      progenitor cell population. As both the in vitro tri-lineage differentiation
      capacity and the in vivo bone forming potential were maintained after 3D
      perfusion bioreactor expansion we concluded that the developed seeding, culture
      and harvest processes did not significantly compromise the viability and potency
      of the cells and can contribute to the future development of integrated
      bioprocesses for stem cell expansion. 

PMID- 26313144
TI  - A Linear Mixed Model Spline Framework for Analysing Time Course 'Omics' Data.
AB  - Time course 'omics' experiments are becoming increasingly important to study
      system-wide dynamic regulation. Despite their high information content, analysis
      remains challenging. 'Omics' technologies capture quantitative measurements on
      tens of thousands of molecules. Therefore, in a time course 'omics' experiment
      molecules are measured for multiple subjects over multiple time points. This
      results in a large, high-dimensional dataset, which requires computationally
      efficient approaches for statistical analysis. Moreover, methods need to be able
      to handle missing values and various levels of noise. We present a novel, robust
      and powerful framework to analyze time course 'omics' data that consists of three
      stages: quality assessment and filtering, profile modelling, and analysis. The
      first step consists of removing molecules for which expression or abundance is
      highly variable over time. The second step models each molecular expression
      profile in a linear mixed model framework which takes into account subject
      specific variability. The best model is selected through a serial model selection
      approach and results in dimension reduction of the time course data. The final
      step includes two types of analysis of the modelled trajectories, namely,
      clustering analysis to identify groups of correlated profiles over time, and
      differential expression analysis to identify profiles which differ over time
      and/or between treatment groups. Through simulation studies we demonstrate the
      high sensitivity and specificity of our approach for differential expression
      analysis. We then illustrate how our framework can bring novel insights on two
      time course 'omics' studies in breast cancer and kidney rejection. The methods
      are publicly available, implemented in the R CRAN package lmms. 

PMID- 26313145
TI  - Effects of Active and Passive Hearing Protection Devices on Sound Source
      Localization, Speech Recognition, and Tone Detection.
AB  - Hearing protection devices (HPDs) such as earplugs offer to mitigate noise
      exposure and reduce the incidence of hearing loss among persons frequently
      exposed to intense sound. However, distortions of spatial acoustic information
      and reduced audibility of low-intensity sounds caused by many existing HPDs can
      make their use untenable in high-risk (e.g., military or law enforcement)
      environments where auditory situational awareness is imperative. Here we assessed
      (1) sound source localization accuracy using a head-turning paradigm, (2) speech
      in-noise recognition using a modified version of the QuickSIN test, and (3) tone
      detection thresholds using a two-alternative forced-choice task. Subjects were 10
      young normal-hearing males. Four different HPDs were tested (two active, two
      passive), including two new and previously untested devices. Relative to
      unoccluded (control) performance, all tested HPDs significantly degraded
      performance across tasks, although one active HPD slightly improved high
      frequency tone detection thresholds and did not degrade speech recognition.
      Behavioral data were examined with respect to head-related transfer functions
      measured using a binaural manikin with and without tested HPDs in place. Data
      reinforce previous reports that HPDs significantly compromise a variety of
      auditory perceptual facilities, particularly sound localization due to
      distortions of high-frequency spectral cues that are important for the avoidance
      of front-back confusions. 

PMID- 26313146
TI  - Correction: Associations of Low-Intensity Resistance Training with Body
      Composition and Lipid Profile in Obese Patients with Type 2 Diabetes.

PMID- 26313148
TI  - The diffuse component of erythemal ultraviolet radiation.
AB  - The diffuse (Dif) component of ultraviolet radiation (UVR) plays an important
      role in the daily exposure of humans to solar radiation. This study proposes a
      semi-empirical method to obtain the Dif component of the erythemal dose rate, or
      the erythemally weighted irradiance, (EDRDif) calculated from synchronized
      measurements of the Dif component of UVR (UVDif) and the global (G) irradiances
      of both UVR (UVG) and the erythemal dose rate (EDRG). Since the study was
      conducted in the tropics, results involve a wide range of solar zenith angles to
      which EDRDif is seasonally dependent. Clouds are the main atmospheric agent
      affecting Dif radiation. The ratio between Dif and G (Dif/G) showed a quadratic
      dependence on cloud cover with a coefficient of determination r(2) = 0.79. The
      maxima of EDRDif were mainly above the moderate range (>137.5 mW m(-2)) of the UV
      Index and reached the extreme range (>262.5 mW m(-2)) for the spring-summer
      period. The fraction of the global daily erythemal dose (daily EDG) corresponding
      to Dif radiation (daily EDDif) ranged from 936 J m(-2) to 5053 J m(-2) and
      averaged 2673 J m(-2). Daily EDDif corresponded to at least 48% of daily EDG for
      a practically cloudless sky. Therefore, Dif radiation is a real threat. Lighter
      skin people (types I and II) can get sunburnt in a couple of minutes under such
      an incidence of radiation. Moreover, accumulative harm can affect all skin types.

PMID- 26313147
TI  - Experiences of General Practitioners and Practice Assistants during the Influenza
      A(H1N1) Pandemic in the Netherlands: A Cross-Sectional Survey.
AB  - OBJECTIVES: Since few pandemics have occurred since the Spanish influenza
      pandemic, we should learn from every (mild) pandemic that occurs. The objective
      of this study was to report on general practitioners' and practice assistants'
      acceptance of the chosen national policy, and experiences in the Netherlands
      during the influenza A(H1N1)pdm09 pandemic. METHODS: Data on experience and
      acceptance of the chosen national policy were obtained by structured
      questionnaires for general practitioners (n = 372) and practice assistants (n =
      503) in April 2010. RESULTS: The primary policy chosen for general practice was
      not always accepted and complied with by general practitioners, although the
      communication (of changes) and collaboration with involved organisations were
      rated as positive. In particular, the advised personal protective measures were
      difficult to implement in daily work and thus not executed by 44% of general
      practitioners. Half of the general practitioners were not satisfied with the
      patient information provided by the government. The influenza A(H1N1) pandemic
      highly impacted on general practitioners' and practice assistants' workloads,
      which was not always deemed to be adequately compensated. DISCUSSION: Involvement
      of general practitioners in future infectious disease outbreaks is essential.
      This study addresses issues in the pandemic policy which might be critical in a
      more severe pandemic.

PMID- 26313138
TI  - Nanoparticle Probes for the Detection of Cancer Biomarkers, Cells, and Tissues by
      Fluorescence.

PMID- 26313149
TI  - Comparative Genomics and Characterization of Hybrid Shigatoxigenic and
      Enterotoxigenic Escherichia coli (STEC/ETEC) Strains.
AB  - BACKGROUND: Shigatoxigenic Escherichia coli (STEC) and enterotoxigenic E. coli
      (ETEC) cause serious foodborne infections in humans. These two pathogroups are
      defined based on the pathogroup-associated virulence genes: stx encoding Shiga
      toxin (Stx) for STEC and elt encoding heat-labile and/or est encoding heat-stable
      enterotoxin (ST) for ETEC. The study investigated the genomics of STEC/ETEC
      hybrid strains to determine their phylogenetic position among E. coli and to
      define the virulence genes they harbor. METHODS: The whole genomes of three
      STEC/ETEC strains possessing both stx and est genes were sequenced using PacBio
      RS sequencer. Two of the strains were isolated from the patients, one with
      hemolytic uremic syndrome, and one with diarrhea. The third strain was of bovine
      origin. Core genome analysis of the shared chromosomal genes and comparison with
      E. coli and Shigella spp. reference genomes was performed to determine the
      phylogenetic position of the STEC/ETEC strains. In addition, a set of virulence
      genes and ETEC colonization factors were extracted from the genomes. The
      production of Stx and ST were studied. RESULTS: The human STEC/ETEC strains
      clustered with strains representing ETEC, STEC, enteroaggregative E. coli, and
      commensal and laboratory-adapted E. coli. However, the bovine STEC/ETEC strain
      formed a remote cluster with two STECs of bovine origin. All three STEC/ETEC
      strains harbored several other virulence genes, apart from stx and est, and
      lacked ETEC colonization factors. Two STEC/ETEC strains produced both toxins and
      one strain Stx only. CONCLUSIONS: This study shows that pathogroup-associated
      virulence genes of different E. coli can co-exist in strains originating from
      different phylogenetic lineages. The possibility of virulence genes to be
      associated with several E. coli pathogroups should be taken into account in
      strain typing and in epidemiological surveillance. Development of novel hybrid E.
      coli strains may cause a new public health risk, which challenges the traditional
      diagnostics of E. coli infections.

PMID- 26313150
TI  - Are Salmonella-Induced Gastroenteritis Neglected in Developing Countries?
      Feedback from Microbiological Investigations in N'Djamena Hospitals, Chad.
AB  - Salmonella is considered to be one of the main pathogens causing human
      gastroenteritis worldwide. Looking for Salmonella in Africa in patients suffering
      from gastroenteritis is rather unusual, and the use of antibiotics is not subject
      to any regulation. This study intends for stressing the possible prominent
      importance of Salmonella in digestive diseases in Africa as well as identifying
      antimicrobial resistance of Salmonella isolates from faeces samples of human
      origin. All samples were collected from five N'Djamena hospitals, from patients
      suffering from diarrhoea. The collecting was undertaken over two periods of six
      months each: from August 2010 to January 2011 and from September 2011 to February
      2012. Salmonella isolates were obtained by standard cultivation and serotyping
      methods. A total of 43 Salmonella isolates were identified, belonging to 21
      different serovars. The most prevalent serovar was Salmonella Stanleyville (n =
      7), followed by S. Anatum (n = 4) and S. Kottbus (n = 3). The other serovars were
      under-represented. The majority of these isolates were susceptible to all
      antibiotics tested (CLSI Standards), except two S. Enteritidis isolates that
      exhibited resistance to fluoroquinolones. The different serovars and antibiotic
      resistance profiles that were observed highlight the substantial diversity of
      Salmonella in N'Djamena, Chad. Roughly, one out of ten patients who consulted for
      gastroenteritis was shedding Salmonella spp. and none of them would have been
      diagnosed outside the context of this research program. This study may encourage
      local clinicians to explore more often salmonellosis suspicion in their daily
      practice. 

PMID- 26313151
TI  - The Changing Epidemiology of Coccidioidomycosis in Los Angeles (LA) County,
      California, 1973-2011.
AB  - Coccidioidomycosis, also known as Valley Fever, is often thought of as an endemic
      disease of central California exclusive of Los Angeles County. The fungus that
      causes Valley Fever, Coccidioides spp., grows in previously undisturbed soil of
      semi-arid and arid environments of certain areas of the Americas. LA County has a
      few large areas with such environments, particularly the Antelope Valley which
      has been having substantial land development. Coccidioidomycosis that is both
      clinically- and laboratory-confirmed is a mandated reportable disease in LA
      County. Population surveillance data for 1973-2011 reveals an annual rate
      increase from 0.87 to 3.2 cases per 100,000 population (n = 61 to 306 annual
      cases). In 2004, case frequency started substantially increasing with notable
      epidemiologic changes such as a rising 2.1 to 5.7 male-to-female case ratio
      stabilizing to 1.4-2.2. Additionally, new building construction in Antelope
      Valley greatly rose in 2003 and displayed a strong correlation (R = 0.92, Pearson
      p<0.0001) with overall LA County incidence rates for 1996-2007. Of the 24 LA
      County health districts, 19 had a 100%-1500% increase in cases when comparing
      2000-2003 to 2008-2011. Case residents of endemic areas had stronger odds of
      local exposures, but cases from areas not known to be endemic had greater
      mortality (14% versus 9%) with notably more deaths during 2008-2011. Compared to
      the 57 other California counties during 2001-2011, LA County had the third
      highest average annual number of cases and Antelope Valley had a higher incidence
      rate than all but six counties. With the large number of reported
      coccidioidomycosis cases, multi-agency and community partnering is recommended to
      develop effective education and prevention strategies to protect residents and
      travelers. 

PMID- 26313152
TI  - IL-6 signaling contributes to cisplatin resistance in non-small cell lung cancer
      via the up-regulation of anti-apoptotic and DNA repair associated molecules.
AB  - Cisplatin-based chemotherapy is currently the most effective treatment regimen
      for non-small cell lung cancer (NSCLC), but eventually tumor resistance develops
      which limits its success. The potential implication of IL-6 signaling in the
      cisplatin resistance of NSCLC was explored by testing whether NSCLC cells with
      different levels of intracellular IL-6 show different responses to the cytotoxic
      treatment of cisplatin. When the cisplatin cytotoxicity of the IL-6 knocked down
      human NSCLC cells (A549IL-6si and H157IL-6si) were compared with their
      corresponding scramble control cells (A549sc and H157sc), higher cisplatin
      cytotoxicity was found in IL-6 si cells than sc cells. Subcutaneous xenograft
      mouse models were developed using a pair of A549sc and A549IL-6si cells. When the
      tumor grew to about 400 mm2, mice were treated with cisplatin and tumor
      regression was monitored. Higher tumor regression was detected in the A549IL-6si
      xenografts compared to A549sc xenografts following cisplatin treatment.
      Immunostaining study results from tumor tissues also supported this finding.
      Expression of anti-apoptotic proteins Bcl-2 and Mcl-1 and DNA repair associated
      molecules ATM, CHK1, TP73, p53, and ERCC1 were significantly up regulated in
      cisplatin-treated A549sc and H157sc cells, but no increase was detected in A549IL
      6si and H157IL-6si cells. Further inhibitor studies revealed that up regulation
      of these molecules by IL-6 may be through activation of IL-6 downstream signaling
      pathways like Akt, MAPK, Stat3, and Erk. These results provide potential for
      combining cisplatin and inhibitors of IL-6 signaling or its downstream signaling
      pathway as a future therapeutic approach in preventing development of cisplatin
      resistant NSCLC tumors. 

PMID- 26313153
TI  - Protein Composition of Infectious Spores Reveals Novel Sexual Development and
      Germination Factors in Cryptococcus.
AB  - Spores are an essential cell type required for long-term survival across diverse
      organisms in the tree of life and are a hallmark of fungal reproduction,
      persistence, and dispersal. Among human fungal pathogens, spores are presumed
      infectious particles, but relatively little is known about this robust cell type.
      Here we used the meningitis-causing fungus Cryptococcus neoformans to determine
      the roles of spore-resident proteins in spore biology. Using highly sensitive
      nanoscale liquid chromatography/mass spectrometry, we compared the proteomes of
      spores and vegetative cells (yeast) and identified eighteen proteins specifically
      enriched in spores. The genes encoding these proteins were deleted, and the
      resulting strains were evaluated for discernable phenotypes. We hypothesized that
      spore-enriched proteins would be preferentially involved in spore-specific
      processes such as dormancy, stress resistance, and germination. Surprisingly,
      however, the majority of the mutants harbored defects in sexual development, the
      process by which spores are formed. One mutant in the cohort was defective in the
      spore-specific process of germination, showing a delay specifically in the
      initiation of vegetative growth. Thus, by using this in-depth proteomics approach
      as a screening tool for cell type-specific proteins and combining it with
      molecular genetics, we successfully identified the first germination factor in C.
      neoformans. We also identified numerous proteins with previously unknown
      functions in both sexual development and spore composition. Our findings provide
      the first insights into the basic protein components of infectious spores and
      reveal unexpected molecular connections between infectious particle production
      and spore composition in a pathogenic eukaryote. 

PMID- 26313154
TI  - Three-Dimensional Environment Sustains Hematopoietic Stem Cell Differentiation
      into Platelet-Producing Megakaryocytes.
AB  - Hematopoietic stem cells (HSC) differentiate into megakaryocytes (MK), whose
      function is to release platelets. Attempts to improve in vitro platelet
      production have been hampered by the low amplification of MK. Providing HSC with
      an optimal three-dimensional (3D) architecture may favor MK differentiation by
      mimicking some crucial functions of the bone marrow structure. To this aim,
      porous hydrogel scaffolds were used to study MK differentiation from HSC as well
      as platelet production. Flow cytometry, qPCR and perfusion studies showed that 3D
      was suitable for longer kinetics of CD34+ cell proliferation and for delayed
      megakaryocytic differentiation far beyond the limited shelf-life observed in
      liquid culture but also increased production of functional platelets. We provide
      evidence that these 3D effects were related to 1) persistence of MK progenitors
      and precursors and 2) prolongation of expression of EKLF and c-myb transcription
      factors involved in early MK differentiation. In addition, presence of abundant
      mature MK with increased ploidy and impressive cytoskeleton elongations was in
      line with expression of NF-E2 transcription factor involved in late MK
      differentiation. Platelets produced in flow conditions were functional as shown
      by integrin alphaIIbbeta3 activation following addition of exogenous agonists.
      This study demonstrates that spatial organization and biological cues synergize
      to improve MK differentiation and platelet production. Thus, 3D environment
      constitutes a powerful tool for unraveling the physiological mechanisms of
      megakaryopoiesis and thrombopoiesis in the bone marrow environment, potentially
      leading to an improved amplification of MK and platelet production. 

PMID- 26313155
TI  - Sticking to traditions: Anatomy education and research in Pakistan.

PMID- 26313156
TI  - Comment on: Carboplatin Hypersensitivity Reactions in Pediatric Low-Grade Glioma
      Are Protocol Specific and Desensitization Shows Poor Efficacy.

PMID- 26313157
TI  - Extended-release but not immediate-release and subcutaneous methylnaltrexone
      antagonizes the loperamide-induced delay of whole-gut transit time in healthy
      subjects.
AB  - Methylnaltrexone (MNTX) is approved for subcutaneous treatment (MNTX-SC) of
      opioid induced constipation. MNTX in oral immediate-release (MNTX-IR) and
      extended-release (MNTX-ER) dosage forms may antagonize the opioid induced delay
      in oro-cecal transit time (OCT) as measured by using radiolabeled lactulose.
      Because lactulose acts laxative by its own and efficacy of MNTX on colon transit
      time (CTT) was unknown, the opioid antagonistic effects MNTX-IR and MNTX-ER (both
      500 mg) relative to MNTX-SC (12 mg) were evaluated in 15 healthy subjects with
      loperamide (LOP, 3 * 4 mg, 12 hourly) induced experimental constipation using the
      sulfasalazine/sulfapyridine method and radio-opaque markers to measure OCT and
      whole gut transit time (WGT). MNTX-ER significantly antagonized the LOP effects
      in 12 of our 15 subjects who responded to LOP with prolongation of WGT by 20.6
      74.1 h (OCT by 0.50-10.5 h, CTT by 18.3-73.6 h). MNTX-SC and MNTX-IR were without
      significant influence. Compared to MNTX-SC, bioavailability of MNTX-IR and MNTX
      ER was 1.53-5.49% and 0.11-1.24%, respectively. MNTX-SC and MNTX-IR achieved
      active serum levels only for ~ 3-5 h. MNTX-ER antagonized the opioid-induced
      delay of CTT most likely by local effects on u-opioid receptors in the colon.

PMID- 26313158
TI  - Exotines A and B, Two Heterodimers of Isopentenyl-Substituted Indole and Coumarin
      Derivatives from Murraya exotica.
AB  - Exotines A and B (1 and 2), two heterodimers of isopentenyl-substituted indole
      and coumarin derivatives linked through a new fused heptacyclic ring system, were
      isolated from the roots of Murraya exotica. Their structures were established by
      comprehensive NMR and MS spectroscopic data analysis, and the absolute
      configurations were determined by single-crystal X-ray crystallographic analysis
      and ECD calculations. Compounds 1 and 2 showed inhibition of nitric oxide
      production in lipopolysaccharide-induced BV-2 microglial cells with IC50 values
      of 9.2 and 39.9 MUM, respectively. 

PMID- 26313159
TI  - A Highly Convergent Total Synthesis of Leustroducsin B.
AB  - Leustroducsin B exhibits a large variety of biological activities and unique
      structural features. An efficient and highly convergent total synthesis of
      Leustroducsin B was achieved in 17 longest linear and 39 total steps by
      disconnecting the molecule into three fragments having similar levels of
      complexity. These pieces were connected via a highly efficient chelate-controlled
      addition of a vinyl zincate to an alpha-hydroxy ketone and a silicon-mediated
      cross-coupling. The stereochemistry of the central and western fragments was set
      catalytically in high yields and excellent de by a zinc-ProPhenol-catalyzed aldol
      reaction and a palladium-catalyzed asymmetric allylic alkylation. 

PMID- 26313160
TI  - Indications of cone beam CT in head and neck imaging.
AB  - CONCLUSION: Cone Beam Computed Tomography (CBCT) can be widely used in imaging of
      bony structures of the anterior and lateral skull base. Significant differences
      of applied dosages result from the different protocols of the various
      indications. OBJECTIVES: CBCT is increasingly being used in head and neck
      imaging. Until now, no precise knowledge about its dedicated usage existed.
      METHODS: All CBCT of 2012 and 2013 were analysed with regard to the technical
      parameters, the performance, and the indication for imaging. RESULTS: In total,
      1862 patients were examined in 2012 and 2013. The top eight indications of the
      anterior skull were (1) chronic rhinosinusitis with disturbed nasal breathing
      (30.3%); (2) chronic rhinosinusitis (17.6%); (3) midfacial traumatology (13.7%);
      (4) disturbed nasal breathing (12.8%); (5) acute rhinosinusitis (7.9%); (6)
      polyposis nasi (6.3%); (7) search for focus (3.9%); and (8) persistent rhinorrhea
      (1.2%). For the lateral skull base, the top eight were (1) control after cochlear
      implantation (28.4%); (2) cholesteatoma (19.7%); (3) visualization of ear anatomy
      (8.7%); (4) chronic otitis media mesotympanalis (6.3%); (5) conductive hearing
      loss (5.1%); (6) suspected mastoiditis (4.8%); (7) pathology of external auditory
      canal (4.8%); and (8) otosclerosis (3.3%). Applied dosage for the anterior skull
      base was significantly lower than for the lateral skull base (2.90 mGy vs 5.92
      mGy, p < 0.05); 2.4% and 3.6% of patients' images, respectively, had to be
      repeated.

PMID- 26313161
TI  - Reaching for Objects or Asking for Them: Distance Estimation in 7- to 15-Year-Old
      Children.
AB  - This study aims to determine if, in children, subjective perception of space is
      modulated by the experience of reaching distal objects by means of tools and
      verbal labels. We presented 7-15-year-old participants with objects located in
      the near and far space, and in the threshold area between these spaces (border
      space). Before and after a training session, separate groups of participants
      estimated objects' location by providing a verbal estimation of their distance (n
      = 12) or by rolling a toy car to match their location (motor-based estimation; n
      = 16). The training session required interaction with the targets (i.e., actively
      experiencing the perceived distance) and included use of a rake or a linguistic
      label when far objects were involved. A control condition in which training
      implied use of a short, ineffective tool was also tested (n = 6). Results showed
      that verbal estimations were not affected by the training phase (p > .05). In
      contrast, training modulated motor-based estimations relative to border space.
      Specifically, maximal distance of toy car displacements was reduced following all
      kinds of training (p < .01). These results indicate that, similarly to adults,
      the boundary between near and far space is not fixed in children and that both
      active tool use and verbal labels can modulate this uncertain boundary. 

PMID- 26313162
TI  - Patients' beliefs and attitudes about their treatment for inflammatory bowel
      disease in Korea.
AB  - BACKGROUND AND AIMS: Adherence to medication during the treatment of inflammatory
      bowel disease (IBD) is important in terms of maintaining remission. According to
      studies on adherence to medication in other chronic diseases, non-adherence is
      associated with negative attitudes to treatment. The aims of this study were to
      assess adherence rates and IBD patients' beliefs and attitudes regarding
      medication using a questionnaire based approach. METHODS: Two hundred and eighty
      seven patients from three tertiary hospitals were enrolled and completed a
      questionnaire that addressed adherence (Medication Adherence Report Scale, MARS),
      beliefs, and attitudes to medication (Beliefs about Medications Questionnaire,
      BMQ). RESULTS: Using a cutoff score of 16/20 for MARS, 64 (22.3%) patients did
      not adhere to medication. According to attitude analysis conducted using the BMQ,
      41.8% of the 287 study subjects felt high necessity but low concern for the
      medication ("accepting") and 34.8% felt high necessity and concern
      ("ambivalent"). Multivariate analysis showed significantly lower adherence to
      medication among younger patients, patients with experience of adverse effects to
      medication, patients with demanding jobs, and for those with an "indifferent" or
      "skeptical" attitude regarding the benefits of medication. On the other hand, IBD
      patients with "accepting" attitude adhered to medication. CONCLUSION: Twenty-two
      percent of IBD patients were non-adherent to medical treatment, and belief of the
      need for medication was found to significantly enhance adherence. Interventions,
      such as education about the efficacy and safety of medications, should be
      considered to facilitate adherence to medical treatment among IBD patients.

PMID- 26313163
TI  - Student assistantship programme in practice: First hand experience at Cardiff
      University.

PMID- 26313164
TI  - Myositis Ossificans in the Thigh of a Lacrosse Player.
AB  - An 18-year-old man presented with mid left thigh pain after sequential lacrosse
      injuries 1 month and 2 weeks prior. Physical examination was significant for a
      tender mass in the mid left thigh. 

PMID- 26313165
TI  - Greater Trochanteric Fragmentation After Failed Metal-on-Metal Hip Arthroplasty.

PMID- 26313166
TI  - The Importance of Resident Engagement in Health Policy.

PMID- 26313167
TI  - Anterior Longitudinal Osteotomy of the Greater Trochanter in Total Hip
      Arthroplasty.
AB  - The extra-articular impingement of the greater trochanter against the ileum is an
      underrated cause of early dislocation in total hip arthroplasty. In this
      preliminary study, the authors assess the effectiveness of an anterior
      longitudinal osteotomy of the greater trochanter for preventing dislocation. A
      total of 115 patients underwent a total hip arthroplasty through a posterolateral
      approach. All patients underwent clinical and radiological follow-up at 1, 3, and
      6 months. No dislocation was reported. All patients demonstrated fast recovery of
      range of motion and walking. No trochanter fractures were observed. The osteotomy
      of the greater trochanter is an effective surgical technique that decreases
      anterior impingement and consequently lowers the dislocation rate in primary
      total hip arthroplasty. [Orthopedics. 2015; 38(8):490-493.]. 

PMID- 26313168
TI  - One-Stage External Fixation Using a Locking Plate: Experience in 116 Tibial
      Fractures.
AB  - The authors report the results of 1-stage external fixation using a locking plate
      in 116 tibial fractures (85 closed and 31 open). The patients were followed for
      an average of 22 months. The mean duration of surgery was 42 minutes. The mean
      fracture healing time was 12 weeks for proximal, 20 weeks for shaft, 14 weeks for
      distal, and 24 weeks for multisegmental tibial fractures. Nonunion, deep
      infection, and breakage of screws did not occur. External plate fixation is
      effective for tibial fractures and especially for metaphyseal fractures. It has
      the advantages of being easy to perform and less invasive, and the plate is
      conveniently located for removal.

PMID- 26313169
TI  - 2-Phenyl-APB-144-Induced Retinal Pigment Epithelium Degeneration and Its
      Underlying Mechanisms.
AB  - PURPOSE: To investigate the efficacy of 2-phenyl-APB-144 (APB)-induced
      retinopathy in a rat model and its underlying mechanisms, with a particular focus
      on retinal pigment epithelium (RPE) degeneration. METHODS: Electroretinograms
      (ERGs) were evaluated in APB-administered rats. In ARPE-19 cells, cathepsin, and
      autophagy marker LC3 were analyzed by western blotting or immunohistochemistry.
      Organelle pH alterations were detected by Acridine Orange Staining. Endoplasmic
      reticulum stress-dependent or -independent cell death signaling was analyzed by
      reporter gene assays of activating transcription factor 4 (ATF4), immunoglobulin
      heavy-chain binding protein (BiP), inositol-requiring enzyme 1alpha (IRE1alpha),
      quantitative reverse transcription-polymerase chain reaction of CHOP mRNA, and
      the effects of pharmacological eukaryotic initiation factor 2alpha (eIF2alpha)
      dephosphorylation inhibitor, Salubrinal. The pharmacological effects of
      Salubrinal were examined by fluorophotometry, electrophysiology, and
      histopathology. RESULTS: APB-induced ERG amplitude reduction and fluorescein
      permeability enhancement into the vitreous body of rats were determined. In ARPE
      19 cells, APB-induced organelle pH alterations, imbalances of procathepsin and
      cathepsin expression, the time-dependent accumulation of LC3-II, and the
      translational activation of ATF4 were determined. Salubrinal protected against
      APB-induced cell death and inhibited ATF4 downstream factor CHOP mRNA induction.
      In APB-induced rat retinopathy, systemic Salubrinal alleviated the enhanced
      fluorescein permeability into the vitreous body from the RPE, the reductions in
      ERG amplitudes, and RPE degeneration. CONCLUSIONS: Organelle pH alterations and
      autophagy impairments are involved in APB-induced RPE cell death. Inhibition of
      eIF2alpha dephosphorylation protected the RPE in vivo and in vitro. These
      findings suggested that APB-induced retinopathy is a valuable animal model for
      exploring the mechanism of RPE-driven retinopathy.

PMID- 26313170
TI  - Albumin Kinetics in Patients Undergoing Major Abdominal Surgery.
AB  - BACKGROUND: The drop in plasma albumin concentration following surgical trauma is
      well known, but the temporal pattern of the detailed mechanisms behind are less
      well described. The aim of this explorative study was to assess changes in
      albumin synthesis and transcapillary escape rate (TER) following major surgical
      trauma, at the time of peak elevations in two well-recognized markers of
      inflammation. METHODS: This was a clinical trial of radiolabeled human serum
      albumin for the study of TER and plasma volume. Ten patients were studied
      immediately preoperatively and on the 2nd postoperative day after major
      pancreatic surgery. Albumin synthesis rate was measured by the flooding dose
      technique employing incorporation of isotopically labelled phenylalanine.
      RESULTS: Fractional synthesis rate of albumin increased from 11.7 (95% CI: 8.9,
      14.5) to 15.0 (11.7, 18.4) %/day (p = 0.027), whereas the corresponding absolute
      synthesis rate was unchanged, 175 (138, 212) versus 150 (107, 192) mg/kg/day (p =
      0.21). TER was unchanged, 4.9 (3.1, 6.8) %/hour versus 5.5 (3.9, 7.2) (p = 0.63).
      Plasma volume was unchanged but plasma albumin decreased from 33.5 (30.9, 36.2)
      to 22.1 (19.8, 24.3) g/L. (p<0.001). CONCLUSION: Two days after major abdominal
      surgery, at the time-point when two biomarkers of generalised inflammation were
      at their peak and the plasma albumin concentration had decreased by 33%, we were
      unable to show any difference in the absolute synthesis rate of albumin, TER and
      plasma volume as compared with values obtained immediately pre-operatively. This
      suggests that capillary leakage, if elevated postoperatively, had ceased at that
      time-point. The temporal relations between albumin kinetics, capillary leakage
      and generalised inflammation need to be further explored. TRIAL REGISTRATION:
      clinicaltrialsregister.eu: EudraCT 2010-08529-21 ClinicalTrials.gov NCT01194492.

PMID- 26313172
TI  - Erratum.

PMID- 26313171
TI  - Discovery of Xuebijing Injection Exhibiting Protective Efficacy on Sepsis by
      Inhibiting the Expression of HMGB1 in Septic Rat Model Designed by Cecal Ligation
      and Puncture.
AB  - Xuebijing (XBJ) injection is a complex traditional Chinese prescription that has
      been widely used to treat sepsis in China. However, its underlying mechanisms on
      sepsis still remain uninvestigated. In this study, 150 male Sprague Dawley rats
      were randomly divided into a normal control group, cecal ligation and puncture
      (CLP) group, CLP+XBJ group, and CLP+gibberellic acid group. Each of them
      contained 3 subgroups of different treatment periods (12, 24, and 48 hours after
      injection, respectively). The mRNA expression of HMGB1 in liver tissue of the 4
      groups was calculated by the semiquantitative reverse-transcription polymerase
      chain reaction. The level of IL-6, IL-10, and TNF-alpha was determined by an
      enzyme-linked immunosorbent assay. Immunohistochemical analysis for HMGB1 showed
      the effect of XBJ on infiltration of inflammatory cells. The mRNA expression of
      HMGB1 in liver tissue in CLP+XBJ and CLP+gibberellic acid groups was lower than
      that in the CLP group. The levels of IL-6, IL-10, and TNF-alpha were decreased at
      the each monitored time point. All these results indicated that XBJ exhibits
      protective efficacy on sepsis by inhibiting the expression of HMGB1.

PMID- 26313173
TI  - Generating Within-Plant Spatial Distributions of an Insect Herbivore Based on
      Aggregation Patterns and Per-Node Infestation Probabilities.
AB  - Most predator-prey models extrapolate functional responses from small-scale
      experiments assuming spatially uniform within-plant predator-prey interactions.
      However, some predators focus their search in certain plant regions, and
      herbivores tend to select leaves to balance their nutrient uptake and exposure to
      plant defenses. Individual-based models that account for heterogeneous within
      plant predator-prey interactions can be used to scale-up functional responses,
      but they would require the generation of explicit prey spatial distributions
      within-plant architecture models. The silverleaf whitefly, Bemisia tabaci biotype
      B (Gennadius) (Hemiptera: Aleyrodidae), is a significant pest of tomato crops
      worldwide that exhibits highly aggregated populations at several spatial scales,
      including within the plant. As part of an analytical framework to understand
      predator-silverleaf whitefly interactions, the objective of this research was to
      develop an algorithm to generate explicit spatial counts of silverleaf whitefly
      nymphs within tomato plants. The algorithm requires the plant size and the number
      of silverleaf whitefly individuals to distribute as inputs, and includes models
      that describe infestation probabilities per leaf nodal position and the
      aggregation pattern of the silverleaf whitefly within tomato plants and leaves.
      The output is a simulated number of silverleaf whitefly individuals for each leaf
      and leaflet on one or more plants. Parameter estimation was performed using nymph
      counts per leaflet censused from 30 artificially infested tomato plants.
      Validation revealed a substantial agreement between algorithm outputs and
      independent data that included the distribution of counts of both eggs and
      nymphs. This algorithm can be used in simulation models that explore the effect
      of local heterogeneity on whitefly-predator dynamics. 

PMID- 26313174
TI  - Potential Overwintering Locations of Soybean Aphid (Hemiptera: Aphididae)
      Colonizing Soybean in Ohio and Wisconsin.
AB  - Soybean aphids, Aphis glycines Matsumura, depend on long-distance, wind-aided
      dispersal to complete their life cycle. Despite our general understanding of
      soybean aphid biology, little is explicitly known about dispersal of soybean
      aphids between winter and summer hosts in North America. This study compared
      genotypic diversity of soybean aphids sampled from several overwintering
      locations in the Midwest and soybean fields in Ohio and Wisconsin to test the
      hypothesis that these overwintering locations are sources of the soybean
      colonists. In addition, air parcel trajectory analyses were used to demonstrate
      the potential for long-distance dispersal events to occur to or from these
      overwintering locations. Results suggest that soybean aphids from overwintering
      locations along the Illinois-Iowa border and northern Indiana-Ohio are potential
      colonists of soybean in Ohio and Wisconsin, but that Ohio is also colonized by
      soybean aphids from other unknown overwintering locations. Soybean aphids in Ohio
      and Wisconsin exhibit a small degree of population structure that is not
      associated with the locations of soybean fields in which they occur, but that may
      be related to specific overwintering environments, multiple introductions to
      North America, or spatial variation in aphid phenology. There may be a limited
      range of suitable habitat for soybean aphid overwintering, in which case
      management of soybean aphids may be more effective at their overwintering sites.
      Further research efforts should focus on discovering more overwintering locations
      of soybean aphid in North America, and the relative impact of short- and long
      distance dispersal events on soybean aphid population dynamics. 

PMID- 26313175
TI  - Species Composition, Distribution, and Seasonal Abundance of Liriomyza Leafminers
      (Diptera: Agromyzidae) Under Different Vegetable Production Systems and
      Agroecological Zones in Kenya.
AB  - A longitudinal study to identify the species of Liriomyza leafminer, their
      distribution, relative abundance, and seasonal variation, including their host
      range, was conducted in vegetable fields at three altitudes in Kenya from
      November 2011 to November 2012. Three main species were identified: Liriomyza
      huidobrensis (Blanchard), Liriomyza sativae Blanchard, and Liriomyza trifolii
      (Burgess), of which L. huidobrensis was the most abundant across all altitudes
      irrespective of the cropping season and accounting for over 90% of the total
      Liriomyza specimens collected. Liriomyza species were collected from all infested
      incubated leaves of 20 crops surveyed belonging to seven families: Fabaceae,
      Solanaceae, Cucurbitaceae, Malvaceae, Brassicaceae, Amaranthaceae, and
      Amaryllidaceae. However, more than 87.5% of the Liriomyza species were obtained
      from only four of these crops: Pisum sativum L., Phaseolus vulgaris L., Solanum
      lycopersicum L., and Solanum tuberosum, thereby demonstrating that Fabaceae and
      Solonaceae crops are the most important hosts with regard to Liriomyza species
      richness and relative abundance. L. huidobrensis had the widest host range (20
      crops), followed by L. sativae (18 crops) and L. trifolii (12 crops). Although L.
      trifolii has been considered the dominant Liriomyza leafminer in Kenya, this
      study suggests that this may not be the case anymore, as L. huidobrensis
      dominates at all altitudes. 

PMID- 26313176
TI  - Species Composition and Abundance of Stink Bugs (Hemiptera: Heteroptera:
      Pentatomidae) in Minnesota Field Corn.
AB  - In response to concerns of increasing significance of stink bugs (Hemiptera:
      Heteroptera: Pentatomidae) in northern states, a survey was conducted over 2 yr
      in Minnesota to characterize the Pentatomidae associated with field corn, Zea
      mays L. Halyomorpha halys (Stal), an exotic species, was not detected in this
      survey, despite continued detection of this species as an invader of human-made
      structures in Minnesota. Five species of Pentatomidae (four herbivorous; one
      predatory) were collected from corn. Across years, Euschistus variolarius
      (Palisot de Beauvois) and Euschistus servus euschistoides (Vollenhoven) had the
      greatest relative abundances and frequencies of detection. In 2012, the abundance
      of herbivorous species exceeded 25 nymphs and adults per 100 plants (i.e., an
      economic threshold) in 0.48% of fields. However, the abundance of herbivorous
      species did not reach economic levels in any fields sampled in 2013. The
      frequency of detection of herbivorous species and ratio of nymphs to adults was
      highest during reproductive growth stages of corn. The predator species, Podisus
      maculiventris (Say), was detected in 0 to 0.32% of fields. These results provide
      baseline information on the species composition and abundance of Pentatomidae in
      Minnesota field corn, which will be necessary for documentation of changes to
      this fauna as a result of the invasion of H. halys and to determine if some
      native species continue to increase in abundance in field crops.

PMID- 26313177
TI  - The Ontogenetically Variable Trophic Niche of a Praying Mantid Revealed by Stable
      Isotope Analysis.
AB  - Praying mantids have been shown to exert strong influences on arthropod community
      composition. However, they may not occupy the same trophic level throughout their
      lives. Trophic shifting over a life cycle could explain the documented variation
      in results from field studies, but specific interactions of predators within food
      webs have been difficult to determine simply by comparing control and treatment
      assemblages in field experiments. We examined the trophic position of the Chinese
      praying mantid, Tenodera aridifolia sinensis (Saussure), using stable isotope
      analysis (SIA). We measured the delta(13)C and delta(15)N of field-collected
      arthropods, and of laboratory groups of mantids fed known diets of these
      arthropods chosen from the most abundant trophic guilds: herbivores (sap feeders
      and plant chewers), and carnivores. We also collected mantids from the field over
      a growing season and compared their SIA values to those of the laboratory groups.
      Both delta(13)C and delta(15)N of mantids fed carnivorous prey (spiders or other
      mantids) were higher than those fed herbivores (grasshoppers). SIA values from
      field-collected mantids were highly variable, and indicated that they did not
      take prey from trophic guilds in proportion to their abundances, i.e., were not
      frequency-dependent predators. Further, delta(15)N decreased from a high at egg
      hatch to a low at the third instar as early nymphs fed mainly on lower trophic
      levels, and increased steadily thereafter as they shifted to feeding on higher
      levels. We suggest that the community impact of generalist predators can be
      strongly influenced by ontogenetic shifts in diet. 

PMID- 26313178
TI  - Functional Response of Three Species of Predatory Pirate Bugs Attacking Eggs of
      Tuta absoluta (Lepidoptera: Gelechiidae).
AB  - The functional response and predation parameters of three species of predatory
      pirate bugs Amphiareus constrictus (Stal), Blaptostethus pallescens Poppius, and
      Orius tristicolor (White) (Hemiptera: Anthocoridae) were evaluated at four
      different densities of eggs of Tuta absoluta (Meyrick) (Lepidoptera:
      Gelechiidae). Experiments were conducted in Petri dishes containing a tomato leaf
      disk infested with the pest eggs, and maintained inside growth chamber with
      environmental conditions of 25 +/- 2  degrees C, 70 +/- 10% relative humidity,
      and a photoperiod of 12:12 (L:D) h. A. constrictus and B. pallescens showed a
      type III functional response where predation increased at a decreasing rate after
      egg density was higher than 12 per leaf disk, reaching an upper plateau of 18.86
      and 25.42 eggs per 24 hours, respectively. By contrast, O. tristicolor showed a
      type II functional response where the number of eggs preyed upon increased at a
      decreasing rate as egg density increased, reaching an upper limit of 15.20 eggs
      per 24 hours. The predator equations used in this study estimated handling time
      of 1.25, 0.87, 0.96 h for A. constrictus, B. pallescens, and O. tristicolor,
      respectively. The lower handling time and possible higher attack rate of B.
      pallescens suggests a higher efficiency and probably greater impact on the pest
      population. If conservation or classical biological control of T. absoluta is to
      be implemented, then prioritizing which natural enemy species is the most
      efficient is an important first step.

PMID- 26313179
TI  - Improving the Performance of the Granulosis Virus of Codling Moth (Lepidoptera:
      Tortricidae) by Adding the Yeast Saccharomyces cerevisiae with Sugar.
AB  - Studies were conducted with the codling moth granulosis virus (CpGV) to evaluate
      whether adding the yeast Saccharomyces cerevisiae Meyen ex E. C. Hansen with
      brown cane sugar could improve larval control of Cydia pomonella (L.). Larval
      mortalities in dipped-apple bioassays with S. cerevisiae or sugar alone were not
      significantly different from the water control. The addition of S. cerevisiae but
      not sugar with CpGV significantly increased larval mortality compared with CpGV
      alone. The combination of S. cerevisiae and sugar with CpGV significantly
      increased larval mortality compared with CpGV plus either additive alone. The
      addition of S. cerevisiae improved the efficacy of CpGV similarly to the use of
      the yeast Metschnikowia pulcherrima (isolated from field-collected larvae). The
      proportion of uninjured fruit in field trials was significantly increased with
      the addition of S. cerevisiae and sugar to CpGV compared with CpGV alone only in
      year 1, and from the controls in both years. In comparison, larval mortality was
      significantly increased in both years with the addition of S. cerevisiae and
      sugar with CpGV compared with CpGV alone or from the controls. The numbers of
      overwintering larvae on trees was significantly reduced from the control
      following a seasonal program of CpGV plus S. cerevisiae and sugar. The addition
      of a microencapsulated formulation of pear ester did not improve the performance
      of CpGV or CpGV plus S. cerevisiae and sugar. These data suggest that yeasts can
      enhance the effectiveness of the biological control agent CpGV, in managing and
      maintaining codling moth at low densities. 

PMID- 26313180
TI  - Biology and Host Range of Digitivalva delaireae (Lepidoptera: Glyphipterigidae),
      a Candidate Agent for Biological Control of Cape-ivy (Delairea odorata) in
      California and Oregon.
AB  - Cape-ivy (Delairea odorata Lemaire) is an ornamental vine native to South Africa
      that has escaped into natural areas in coastal California and Oregon, displacing
      native vegetation. Surveys in South Africa led to the discovery of the leaf- and
      stem-mining moth Digitivalva delaireae Gaedike and Kruger (Lepidoptera:
      Glyphipterigidae: Acrolepiinae) as one of several common and damaging native
      herbivores on Cape-ivy. In greenhouse studies, adult female life span averaged 16
      d (46 d maximum). Most (72%) mated females began laying eggs within 72 h of
      emergence. Females had an average lifetime fecundity of 52 eggs, with >70% laid
      on leaf laminae, and 89% of eggs were laid by the 15th day postemergence.
      Lifetime fertility (adult production) averaged three to four offspring per
      female. At 25  degrees C, egg hatch required 10 d, pupal formation 26 d, and
      adult emergence 41 d, while under variable greenhouse and laboratory conditions
      development to adult required 54-60 d. In four-way choice tests, involving 100
      plant species other than Cape-ivy, including 11 genera and 37 species in the
      Asteraceae, subtribe Senecioninae from both native and invaded ranges, D.
      delaireae inflicted damage and produced pupae only on Cape-ivy. Leaf mining
      damage occurred on 30% of leaves of native Senecio hydrophilus in no-choice tests
      and on 2% of leaves in dual-choice tests, but no pupation occurred. If approved
      for field release in the continental United States, the moth D. delaireae is
      expected to produce multiple generations per year on Cape-ivy, and to pose little
      risk of damage to native plants.

PMID- 26313181
TI  - Climate Change and Tritrophic Interactions: Will Modifications to Greenhouse Gas
      Emissions Increase the Vulnerability of Herbivorous Insects to Natural Enemies?
AB  - Insects are highly dependent on odor cues released into the environment to locate
      conspecifics or food sources. This mechanism is particularly important for insect
      predators that rely on kairomones released by their prey to detect them. In the
      context of climate change and, more specifically, modifications in the gas
      composition of the atmosphere, chemical communication-mediating interactions
      between phytophagous insect pests, their host plants, and their natural enemies
      is likely to be impacted. Several reports have indicated that modifications to
      plants caused by elevated carbon dioxide and ozone concentrations might
      indirectly affect insect herbivores, with community-level modifications to this
      group potentially having an indirect influence on higher trophic levels. The
      vulnerability of agricultural insect pests toward their natural enemies under
      elevated greenhouse gases concentrations has been frequently reported, but
      conflicting results have been obtained. This literature review shows that the
      higher levels of carbon dioxide, as predicted for the coming century, do not
      enhance the abundance or efficiency of natural enemies to locate hosts or prey in
      most published studies. Increased ozone levels lead to modifications in herbivore
      induced volatile organic compounds (VOCs) released by damaged plants, which may
      impact the attractiveness of these herbivores to the third trophic level.
      Furthermore, other oxidative gases (such as SO2 and NO2) tend to reduce the
      abundance of natural enemies. The impact of changes in atmospheric gas emissions
      on plant-insect and insect-insect chemical communication has been under
      documented, despite the significance of these mechanisms in tritrophic
      interactions. We conclude by suggesting some further prospects on this topic of
      research yet to be investigated. 

PMID- 26313182
TI  - Host Resistance of Five Fraxinus Species to Agrilus planipennis (Coleoptera:
      Buprestidae) and Effects of Paclobutrazol and Fertilization.
AB  - Agrilus planipennis Fairmaire (Coleoptera: Buprestidae) has killed millions of
      Fraxinus spp. trees in North America. While all Fraxinus species assessed to date
      can be colonized, A. planipennis attraction to host trees varies among species
      and with tree health. We established a plantation of 105 trees (21 trees each of
      four North American species Fraxinus americana L., Fraxinus nigra Marshall,
      Fraxinus pennsylvanica Marshall, Fraxinus quadrangulata Michaux, and the Asian
      species, Fraxinus mandshurica Ruprecht), and determined whether resistance to A.
      planipennis could be enhanced by fertilizer or paclobutrazol applications.
      Differences among species overshadowed most treatment effects. In 2010, A.
      planipennis survival over 14 d was 53% when beetles were caged with F. nigra, 30
      32% when beetles were caged with F. americana, F. pennsylvanica, or F.
      mandshurica, and only 14% for beetles caged with F. quadrangulata. In 2011,
      beetle survival was lower for beetles caged with F. quadrangulata (33%) than F.
      americana (72%) or F. mandshurica (80%). In 2010 and 2011, leaf weight consumed
      by beetles was the same among Fraxinus species. However, beetles caged on F.
      quadrangulata consumed less leaf area than that by beetles caged with other ash
      species. In 2011, when trees were exposed to wild A. planipennis, larval density
      (per m(2)) was highest on F. nigra (235.9 +/- 36.41) and F. pennsylvanica (220.1
      +/- 39.77), intermediate on F. americana (40.7 +/- 11.61), and lowest on F.
      quadrangulata and F. mandshurica (2.0 +/- 0.98 and 1.5 +/- 0.67, respectively).
      Results indicate F. quadrangulata and F. mandshurica were relatively resistant to
      A. planipennis, F. nigra and F. pennsylvanica were highly vulnerable, and F.
      americana was intermediate.

PMID- 26313183
TI  - Interhaplotype Fertility and Effects of Host Plant on Reproductive Traits of
      Three Haplotypes of Bactericera cockerelli (Hemiptera: Triozidae).
AB  - Potato psyllid, Bactericera cockerelli (Sulc) (Hemiptera: Triozidae), is a
      serious pest of solanaceous crops in North and Central America and New Zealand.
      This insect vectors the bacterium that causes zebra chip disease of potato
      (Solanum tuberosum L.). Four distinct genetic populations, or haplotypes, of B.
      cockerelli have been identified. Three of the haplotypes may co-occur in potato
      fields in the Pacific Northwest of United States. Solanaceous weeds, including
      the perennial Solanum dulcamara (bittersweet nightshade), may provide refuge for
      psyllid populations which then migrate to potato crops. This study tested whether
      fecundity, fertility (% egg hatch), and adult longevity of potato psyllid were
      affected by host plant (S. dulcamara or potato) and whether these reproductive
      traits were similar among the three haplotypes that are most common in the Pacfic
      Northwest: Northwestern, Central, and Western. We hypothesized that the locally
      resident haplotype (Northwestern), which is known to overwinter extensively on S.
      dulcamara, would show relatively higher fitness on nightshade than the other two
      haplotypes. Fecundity differed significantly among haplotypes, with an average
      lifetime fecundity of 1050, 877, and 629 eggs for Northwestern, Western, and
      Central females, respectively. Egg hatch was significantly reduced in psyllids
      reared on bittersweet nightshade (61.9%) versus potato (81.3%). Adult psyllids
      lived longer on nightshade than on potato, averaging 113.9 and 108.4 d on
      nightshade and 79.0 and 85.5 d on potato for males and females, respectively.
      However, the longer life span of psyllids on nightshade than potato failed to
      lead to higher fecundity, because females on nightshade often ended egglaying
      well before death, unlike those on potato. There was no evidence for any of the
      fitness traits to suggest that the locally resident haplotype (Northwestern)
      performed relatively better on nightshade than the other two haplotypes. Lastly,
      we examined whether mating between psyllids of different haplotypes affected
      sperm transfer and egg hatch rates. Females of the Northwestern haplotype failed
      to produce viable eggs when mated by males of either the Western or Central
      haplotypes.

PMID- 26313185
TI  - Conspecific and Heterospecific Aboveground Herbivory Both Reduce Preference by a
      Belowground Herbivore.
AB  - Insect herbivores damage plants both above- and belowground, and interactions in
      each realm can influence the other via shared hosts. While effects of leaf damage
      on aboveground interactions have been well-documented, studies examining leaf
      damage effects on belowground interactions are limited, and mechanisms for these
      indirect interactions are poorly understood. We examined how leaf herbivory
      affects preference of root-feeding larvae [Acalymma vittatum F. (Coleoptera:
      Chrysomelidae)] in cucumber (Cucumis sativus L.). We manipulated leaf herbivory
      using conspecific adult A. vittatum and heterospecific larval Spodoptera
      frugiperda Smith (Lepidoptera: Noctuidae) herbivores in the greenhouse and the
      conspecific only in the field, allowing larvae to choose between roots of damaged
      and undamaged plants. We also examined whether leaf herbivory induced changes in
      defensive cucurbitacin C in leaves and roots. We hypothesized that induced
      changes in roots would deter larvae, and that effects would be stronger for
      damage by conspecifics than the unrelated caterpillar because the aboveground
      damage could be a cue to plants indicating future root damage by the same
      species. In both the greenhouse and field, plants with damaged leaves recruited
      significantly fewer larvae to their roots than undamaged plants. Effects of
      conspecific and heterospecific damage did not differ. Leaf damage did not induce
      changes in leaf or root cucurbitacin C, but did reduce root biomass. While past
      work has suggested that systemic induction by aboveground herbivory increases
      resistance in roots, our results suggest that decreased preference by belowground
      herbivores in this system may be because of reduced root growth. 

PMID- 26313184
TI  - Striped Cucumber Beetle (Coleoptera: Chrysomelidae) Aggregation in Response to
      Cultivar and Flowering.
AB  - The striped cucumber beetle [Acalymma vittatum (F.)] is a specialist pest of
      cucurbits throughout its range in the United States and Canada. Improved
      integrated pest management options are needed across the pest's range, especially
      on organic farms where there are few effective controls. Trap cropping in
      cucurbits is an option, but there are significant challenges to the technique.
      Because cucurbit flowers are highly attractive to the beetles, four field
      experiments tested whether cultivar and phenology interact to preferentially
      aggregate beetles. The first experiment tested the hypothesis that cucurbit
      flowers were more attractive to striped cucumber beetles than was foliage. The
      second experiment tested whether there were differences in beetle aggregation
      between two relatively attractive cultivars. The third and fourth experiments
      were factorial designs with two plant cultivars and two levels of flowering to
      specifically test for an interaction of cultivar and flowering. Results indicated
      that flowers were more attractive than foliage, beetle aggregation was affected
      by plant cultivar, and that there was an interaction of cultivar with flowering.
      We conclude that a single cultivar may be sufficient to serve as a generic trap
      crop to protect a wide variety of cucurbits. 

PMID- 26313186
TI  - The Impact of Environmental Conditions on Efficiency of Host Plant DNA Barcoding
      for Polyphagous Beetles.
AB  - Recently, several papers were published dealing with host plant identification
      for selected species of insects, including beetles. These studies took advantage
      of the DNA barcoding approach and generally showed that it is possible to
      identify diet composition from plant DNA present in insect guts. However, none of
      these studies considered how the impact of environmental conditions affected the
      likelihood of insect feeding and, therefore, the presence of host plant DNA that
      could be amplified and sequenced. In the present study, individuals of the
      polyphagous weevil Centricnemus leucogrammus (Germar, 1824) (Curculionidae:
      Entiminae) were used to test the hypothesis that harsh environmental conditions
      limited its feeding activity. The diet of 50 specimens collected during
      favourable conditions in the middle of the species reproductive period was
      compared against the diet of 50 specimens collected during harsh environmental
      conditions. Results clearly showed that almost no weevils fed during rainy and
      cold conditions and only a minority of individuals (20%) fed during the drought
      condition (on drought-resistant plants). It is important to consider such factors
      in any studies dealing with host plant identification and feeding behaviour.
      Results of ecological studies could lead to erroneous conclusions, e.g.,
      underestimation of number and composition of host plants in the diet of studies
      species. 

PMID- 26313187
TI  - Comparison of Host-Seeking Behavior of the Filth Fly Pupal Parasitoids, Spalangia
      cameroni and Muscidifurax raptor (Hymenoptera: Pteromalidae).
AB  - The pupal parasitoids, Spalangia cameroni Perkins and Muscidifurax raptor Girault
      and Sanders, can be purchased for biological control of house flies Musca
      domestica L. and stable flies Stomoxys calcitrans (L.) (Diptera: Muscidae).
      Little is known about the odors involved in host-seeking behavior of these two
      species, so odors associated with house flies were investigated in the laboratory
      using a Y-tube olfactometer. Odor stimuli from house fly host puparia, larvae,
      pine-shavings bedding with horse manure, and developing flies in the pine
      shavings-manure substrate were evaluated in bioassays using the two pteromalid
      species. In choice tests, naive female S. cameroni were strongly attracted to
      odor from the substrate containing house fly larvae and secondarily from the
      uninfested substrate and substrate with puparia versus humidified and purified
      air. This species also selected the substrate with larvae versus the substrate
      with the house fly puparia or uninfested substrate. Muscidifurax raptor was
      attracted to odor from the substrate containing puparia, washed puparia, and
      substrate with puparia removed. The data suggest that coexistence between the two
      pteromalid parasitoids, S. cameroni and M. raptor, might be promoted by different
      host-seeking behavior. 

PMID- 26313188
TI  - Response of Adult Plum Curculios (Coleoptera: Curculionidae) to Contrasting
      Shades in Field and Laboratory Experiments.
AB  - The responses of adult plum curculios, Conotrachelus nenuphar (Herbst), to visual
      stimuli were assessed in field and laboratory conditions to evaluate the
      hypothesis that adult captures should increase when traps visually contrast with
      a lighter horizon, such as the sky. Release-recapture field studies tested
      whether adult responses to traps were influenced by the trap's visual contrast
      with background on the horizon. Results at four sites showed that significantly
      more adults were captured in traps with woodlots behind them, refuting the
      hypothesis. Laboratory tests in environmental conditions of 315 lux or less
      observed the movement of adults between intervals. These showed that
      significantly more females and males relocated in areas marked with black. This
      effect occurred when adults were presented with black surfaces, stripes, or
      lines. The black shade used correlated with lower reflected lux (<110), and when
      in conditions of <= 10 lux, significant adult relocation on black was not
      observed. These results suggest that adults arrest in or move toward areas with
      low reflected lux. The laboratory and field results combined suggest that higher
      adult captures in traps correlated with the largest areas of low lux on the
      horizon. The results imply that trap placement should take reflected lux from all
      nearby objects into account and that even in small patterns on traps, variance in
      shade or reflected lux may permit manipulation of plum curculio movement.

PMID- 26313189
TI  - Nonconsumptive Predator-Prey Interactions: Sensitivity of the Detritivore Sinella
      curviseta (Collembola: Entomobryidae) to Cues of Predation Risk From the Spider
      Pardosa milvina (Araneae: Lycosidae).
AB  - Predators can affect prey indirectly when prey respond to cues indicating a risk
      of predation by altering activity levels. Changes in prey behavior may cascade
      through the food web to influence ecosystem function. The response of the
      collembolan Sinella curviseta Brook (Collembola: Entomobryidae) to cues
      indicating predation risk (necromones and cues from the wolf spider Pardosa
      milvina (Hentz) (Araneae: Lycosidae)) was tested. Additionally, necromones and
      predator cues were paired in a conditioning experiment to determine whether the
      collembolan could form learned associations. Although collembolans did not alter
      activity levels in response to predator cues, numerous aspects of behavior
      differed in the presence of necromones. There was no detectable conditioned
      response to predator cues after pairing with necromones. These results provide
      insight into how collembolans perceive and respond to predation threats that vary
      in information content. Previously detected indirect impacts of predator cues on
      ecosystem function are likely due to changes in prey other than activity level. 

PMID- 26313190
TI  - Behavioral and Antennal Responses of Drosophila suzukii (Diptera: Drosophilidae)
      to Volatiles From Fruit Extracts.
AB  - Native to Southeast Asia, the spotted wing drosophila, Drosophila suzukii
      Matsumura (Diptera: Drosophilidae), has become a serious pest of soft-skinned
      fruit crops since its introduction into North America and Europe in 2008. Current
      monitoring strategies use baits based on fermentation products; however, to date,
      no fruit-based volatile blends attractive to this fly have been identified. This
      is particularly important because females are able to cut into the epicarp of
      ripening fruit for oviposition. Thus, we conducted studies to: 1) investigate the
      behavioral responses of adult D. suzukii to volatiles from blueberry, cherry,
      raspberry, and strawberry fruit extracts; 2) identify the antennally active
      compounds from the most attractive among the tested extracts (raspberry) using
      gas chromatography (GC)-mass spectrometry and coupled gas chromatography 
      electroantennographic detection (GC-EAD); and 3) test a synthetic blend
      containing the EAD-active compounds identified from raspberry extract on adult
      attraction. In olfactometer studies, both female and male D. suzukii were
      attracted to all four fruit extracts. The attractiveness of the fruit extracts
      ranks as: raspberry >= strawberry > blueberry >= cherry. GC analyses showed that
      the fruit extracts emit distinct volatile compounds. In GC-EAD experiments, 11
      raspberry extract volatiles consistently elicited antennal responses in D.
      suzukii. In choice test bioassays, a synthetic EAD-active blend attracted more D.
      suzukii than a blank control, but was not as attractive as the raspberry extract.
      To our knowledge, this is the first report of a behaviorally and antennally
      active blend of host fruit volatiles attractive to D. suzukii, offering promising
      opportunities for the development of improved monitoring and behaviourally based
      management tools. 

PMID- 26313191
TI  - Effects of Temperature on the Life Table Parameters of Trichogramma zahiri
      (Hymenoptera: Trichogrammatidae), an Egg Parasitoid of Dicladispa armigera
      (Chrysomelidae: Coleoptera).
AB  - The influence of different temperatures on biological parameters of native
      strains of Trichogramma zahiri Polaszek (Hymenoptera: Trichogrammatidae), an egg
      parasitoid of rice hispa, Dicladispa armigera (Olivier) (Chrysomelidae:
      Coleoptera), was evaluated in the laboratory on its host. The key biological
      parameters of the parasitoid T. zahiri in relation to temperature were
      investigated to find out its candidature as a potential biological control agent
      of rice hispa. The highest number of eggs parasitized by T. zahiri was 15.7 eggs
      per female at 26  degrees C, which differed significantly from those at 18, 22,
      30, and 34  degrees C (P < 0.05). Development duration and longevity of T. zahiri
      decreased as temperature increased. Fecundity differed significantly at all
      constant temperatures. Emergence rates decreased at both high (34  degrees C) and
      low ( < 26  degrees C) temperatures. Female-biased sex ratio ranged from 54 to
      70% at all constant temperatures. The lower temperature threshold for T. zahiri
      was 6.2  degrees C for males and 6.95  degrees C for females. The upper threshold
      temperatures were 35.82 and 35.87  degrees C for males and females, respectively.
      Net reproductive rate (R0) was highest at 26  degrees C compared with other
      temperatures. Mean cohort generation time (tG) and population doubling time (tD)
      decreased as temperature increased from 18 to 30  degrees C. The daily intrinsic
      rate of increase (rm) and finite rate of increase (lambda) were positively
      correlated with temperatures ranging from 18 to 30  degrees C and then decreased
      at 34  degrees C. The relevance of our results is discussed in the context of
      climatic adaptation and biological control.

PMID- 26313192
TI  - Temperature-Mediated Effects of Host Alternation on the Adaptation of Myzus
      persicae (Hemiptera: Aphididae).
AB  - Local adaptation, an important phenomenon in ecological speciation, occurs in
      Myzus persicae (Sulzer), with the tobacco-adapted line proposed as a subspecies.
      Recent studies showed that temperature could alter the selection strength and
      direction in host-herbivore interactions. To understand the formation of host
      adapted speciation and the effects of temperature on host adaptation, the
      parthenogenetic progeny of an M. persicae egg were conditioned on two hosts for
      >10 generations. Then, their life table parameters were studied after reciprocal
      transfer under a temperature gradient. The results showed that aphids habituated
      on tobacco (Nicotiana tabacum L.) and rape (Brassica napus L.) had different
      optimal temperatures, including different upper thresholds of development and
      reproduction on original and alternative hosts. After habituation for >10
      generations, local adaptation of aphids on the host of origin was formed, which
      was observed as the better performance of the native aphids compared with the
      foreign ones. The M. persicae that habituated on rape appeared more generalized
      to the host plants than the aphids that habituated on tobacco. The adaptation
      patterns of green peach aphids on two hosts varied differentially according to
      temperature, which verified the temperature-mediated effects of host selection on
      herbivores, implying the presence of a demographic basis of aphid seasonal
      migration. 

PMID- 26313193
TI  - Temperature-Dependent Development and Reproductive Traits of Tyrophagus
      putrescentiae (Sarcoptiformes: Acaridae) Reared on Different Edible Mushrooms.
AB  - China is the largest producer, consumer, and exporter of mushrooms in the world.
      The storage mite, Tyrophagus putrescentiae Schrank, is one of the most important
      arthropod pests in mushroom cultivation. This study investigated the development
      and reproductive traits of this mite reared on four mushroom species: Agaricus
      bisporus Lange, Pleurotus ostreatus Kumm, Auricularia polytricha (Mont.) Sacc.,
      and Flammulina velutipes (Fr.) Sing., at seven constant temperatures ranging from
      16 to 34  degrees C at 80% relative humidity. Development time for the immature
      stages decreased with increasing temperature, and was also significantly affected
      by mushroom species. The shortest immature developmental period (7.0 +/- 0.2 d)
      was observed at 31  degrees C when reared on F. velutipes, while the longest
      development was at 16  degrees C (36.0 +/- 0.3 d) reared on P. ostreatus. The
      effects of temperature and mushroom hosts on the development, female longevity,
      and reproduction were also significant. The lower threshold temperatures from egg
      to-adult for the four mushroom species were 11.97, 12.02, 10.80, and 11.57 
      degrees C, for A. bisporus, P. ostreatus, Au. polytricha, and F. velutipes, and
      the thermal constants were 133.3, 136.8, 165.2, and 135.9 degree days ( degrees C
      d), for the same mushroom species, respectively. Life table parameters at 25 
      degrees C were estimated as follows: net reproductive rates (R0), 59.16, 28.94,
      42.62, and 62.93, and intrinsic rate of natural increase (rm), 0.24, 0.13, 0.17,
      and 0.24, respectively. These results suggest that these mushrooms are suitable
      hosts for T. putrescentiae, and the storage mite may be able to adapt to higher
      temperatures.

PMID- 26313194
TI  - Temperature-Mediated Development Thresholds of Sparganothis sulfureana
      (Lepidoptera: Tortricidae) in Cranberries.
AB  - Larvae of Sparganothis sulfureana Clemens frequently attack cranberries, often
      resulting in economic damage to the crop. Because temperature dictates insect
      growth rate, development can be accurately estimated based on daily temperature
      measurements. To better predict S. sulfureana development across the growing
      season, we investigated the temperature range within which S. sulfureana larvae
      can feed and grow. Larvae were reared at 13 constant temperatures ranging from
      6.5-38.6  degrees C. Larval growth rate was determined by the rate of change of
      larval weight across time. The respective growth rates among these temperatures
      were modeled using simple linear, cubic, and Lactin nonlinear development
      functions. These models isolated the lower temperature threshold at which growth
      became nonzero and the upper temperature at which growth was maximized. All three
      models were significantly predictive of S. sulfureana growth, but the cubic model
      best represented the observed growth rates, effectively isolating lower and upper
      thresholds of 9.97 and 29.89  degrees C, respectively. We propose that these
      thresholds be used to create a degree-day model of temperature-mediated S.
      sulfureana development.

PMID- 26313195
TI  - Ability of Black Soldier Fly (Diptera: Stratiomyidae) Larvae to Recycle Food
      Waste.
AB  - Accumulation of organic wastes, especially in livestock facilities, can be a
      potential pollution issue. The black soldier fly, Hermetia illucens L. (Diptera:
      Stratiomyidae), can consume a wide range of organic material and has the
      potential to be used in waste management. In addition, the prepupae stage of this
      insect can be harvested and used as a valuable nutritious feed for animal
      livestock. Five waste types with a wide range of organic source matter were
      specifically chosen to evaluate the consumption and reduction ability of black
      soldier fly larvae. H. illucens was able to reduce all waste types examined: 1)
      control poultry feed, 2) pig liver, 3) pig manure, 4) kitchen waste, 5) fruits
      and vegetables, and 6) rendered fish. Kitchen waste had the greatest mean rate of
      reduction (consumption by black soldier fly) per day and produced the longest and
      heaviest black soldier flies. Larvae reared on liver, manure, fruits and
      vegetables, and fish were approximately the same length and weight as larvae fed
      the control feed, although some diets produced larvae with a higher nutritional
      content. The black soldier fly has the ability to consume and reduce organic
      waste and be utilized as valuable animal feed. Exploration of the potential use
      of black soldier flies as an agent for waste management on a large-scale system
      should continue. 

PMID- 26313196
TI  - Preoverwintering Copulation and Female Ratio Bias: Life History Characteristics
      Contributing to the Invasiveness and Rapid Spread of Megacopta cribraria
      (Heteroptera: Plataspidae).
AB  - Prewinter copulation, sperm storage, and oocyte development in overwintering
      adult Megacopta cribraria (F.) was examined in Alabama (Lee Co.). Microscopic
      examinations of the spermathecae and ovaries were made in females and of the
      testes in males that were collected approximately weekly from September 2013
      through March 2014. The results indicated that approximately 15% of females mated
      before entering winter dormancy and sperm was stored in their spermatheca for up
      to seven months, oocytes in mated overwintering females proceeded to
      postblastoderm stage before the onset of spring feeding and mating in March, all
      of the overwintering males had sperm in their testes, and the ratio of females
      gradually increased in populations during overwintering. This study indicates
      that both males and females are capable of reproductive dormancy. The biological
      significance of these life cycle aspects is discussed from the viewpoints of
      invasiveness and adaptation. 

PMID- 26313197
TI  - Evaluation of Reference Genes for RT-qPCR in Tribolium castaneum (Coleoptera:
      Tenebrionidae) Under UVB Stress.
AB  - Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) has become
      a widely used technique to quantify gene expression. It is necessary to select
      appropriate reference genes for normalization. In the present study, we assessed
      the expression stability of seven candidate genes in Tribolium castaneum (Herbst)
      (Coleoptera: Tenebrionidae) irradiated by ultraviolet B (UVB) at different
      developmental stages for various irradiation time periods. The algorithms of
      geNorm, NormFinder, and BestKeeper were applied to determine the stability of
      these candidate genes. Ribosomal protein genes RpS3, RpL13A, and beta-actin gene
      (ActB) showed the highest stability across all UVB irradiation time points,
      whereas expression of other normally used reference genes, such as those encoding
      the beta-tubulin gene TUBB and the E-cadherin gene CAD, varied at different
      developmental stages. This study will potentially provide more suitable reference
      gene candidates for RT-qPCR analysis in T. castaneum subjected to environmental
      stresses, particularly UV irradiation. 

PMID- 26313205
TI  - Erratum.

PMID- 26313203
TI  - Critical Care Utilization for Those With Cancer: How Much Is Enough?

PMID- 26313206
TI  - Surgical resolution of accidental intramuscular injection of Gudair(r) vaccine in
      a mare.
AB  - This case report describes the accidental intramuscular administration of 20 mL
      Gudair(r) vaccine to a 7-year-old Standardbred mare and successful treatment of
      the resulting inflammatory reaction by radical surgical resection.

PMID- 26313207
TI  - Suspected ivermectin resistance in a south-east Queensland Parascaris equorum
      population.
AB  - BACKGROUND: There have been several international reports of macrocyclic lactone
      (ML)-resistant Parascaris equorum over the past decade, but the resistance status
      of Australian P. equorum populations is largely unknown. A case of apparent
      reduced efficacy of ivermectin against P. equorum in Australia was investigated.
      METHODS AND RESULTS: A faecal egg count reduction test carried out on a group of
      weanling foals in south-east Queensland showed the efficacy of ivermectin to be
      65%. CONCLUSION: The case highlights the need to review current worm control
      strategies, especially for young horses.

PMID- 26313208
TI  - Suicide in veterinarians and veterinary nurses in Australia: 2001-2012.
AB  - BACKGROUND: Whether veterinarians have an elevated suicide rate compared with the
      general population is controversial. METHODS: Reported cases of suicide among
      veterinarians and veterinary nurses in Australia over the period 2001 to 2012
      were investigated in a retrospective case-series study. RESULTS: The standardised
      mortality ratio of veterinarians (n = 18) was 1.92 (95% CI 1.14-3.03) and that of
      veterinary nurses (n = 7) to the general population was 1.24 (95% CI 0.80-1.85).
      Overdosing on drugs (pentobarbitone) was the main method of suicide in these
      occupations. CONCLUSION: The reasons for veterinary suicides are likely to be
      multifactorial, including work- and life-related stressors, and individual
      characteristics. This research highlights the need for targeted suicide
      prevention and intervention for veterinarians.

PMID- 26313209
TI  - Repair of sacral fractures using pins and polymethylmethacrylate (six cases).
AB  - CASE REPORTS: Sacral fracture repair was accomplished in a cat and five dogs
      using a composite technique consisting of pins and polymethylmethacrylate (PMMA).
      In three of the cases, planned traditional iliosacral lag screw fixation was
      either abandoned or considered inadequate and in the other three, fracture
      configuration demanded an alternate repair method. All six cases healed
      uneventfully with no surgery-associated complications. To the author's knowledge,
      the use of a composite technique has been previously described for vertebral
      fracture repair, but not in the stabilisation of sacral fractures. Indications
      for the composite technique include failed iliosacral lag screw repairs,
      augmentation of a tenuous repair and any sacral fracture configuration not
      amenable to lag screw fixation. CONCLUSION: Composite repair is a versatile
      primary, ancillary or revision technique for sacral fracture fixation.

PMID- 26313210
TI  - Presumed secondary immune-mediated haemolytic anaemia following elapid snake
      envenomation and its treatment in four dogs.
AB  - CASE SERIES: This case series describes secondary immune-mediated haemolytic
      anaemia (IMHA) in four dogs following elapid snake envenomation and its
      treatment. All the dogs initially presented with clinical signs commensurate with
      mainland tiger snake (Notechis scutatus) envenomation. None of the dogs was
      anaemic at the time of presentation. IMHA was diagnosed 3-9 days following snake
      envenomation. The trigger for IMHA was unclear in each case and may have been a
      component of the snake venom, antivenom, fresh frozen plasma, concurrent
      morbidity, administered drugs or a combination thereof. Three of the four dogs
      received immunosuppressive therapy comprising corticosteroids with or without
      azathioprine. Resolution of the IMHA was documented 6 weeks after diagnosis for
      one dog and 9 months after diagnosis for two dogs, with one dog lost to follow
      up. CONCLUSION: IMHA is a potential complicating factor of elapid snake
      envenomation and its treatment in dogs, and should be considered as a
      differential diagnosis for a persistent or worsening anaemia. Both the incidence
      and aetiopathogenesis of IMHA in the context of elapid snake envenomation and its
      treatment in dogs are unknown and require further examination.

PMID- 26313211
TI  - Adrenal insufficiency secondary to lymphocytic panhypophysitis in a cat.
AB  - CASE REPORT: A 13-year-old male castrated Domestic Shorthair cat was presented
      for investigation of lethargy, vomiting, polydipsia and polyuria. Glucocorticoid
      deficient hypoadrenocorticism was suspected based on hypocholesterolaemia,
      hypoglycaemia and lack of a stress leucogram, and confirmed with an ACTH
      stimulation test. Pituitary disease was suspected based on the clinical signs and
      the combination of hyposthenuria and hypernatraemia. Necropsy revealed
      bilaterally symmetric adrenocortical atrophy and the changes in the pituitary
      gland were suggestive of a T-cell-rich immune-mediated panhypophysitis. CLINICAL
      SIGNIFICANCE: Secondary adrenal insufficiency and panhypophysitis have not been
      previously reported in the cat. This report should raise awareness of this rare
      but potentially treatable disease process.

PMID- 26313213
TI  - Top tips for veterinary practice websites.

PMID- 26313212
TI  - Marked struvite crystalluria and its association with lower urinary tract signs
      in a cat with feline idiopathic cystitis.
AB  - CASE REPORT: We describe a case of a large amount of mineralised material,
      presumed to be struvite crystals, within the urinary bladder of a cat with feline
      idiopathic cystitis. The presence of this material coincided with episodes of
      lower urinary tract signs in this cat over a 2-year period. CLINICAL
      SIGNIFICANCE: Although struvite crystalluria is widely considered to be
      clinically insignificant, this generalisation may not be true for all cats with
      lower urinary tract disease. Imaging of the urinary tract is recommended in all
      cats with lower urinary tract signs.

PMID- 26313214
TI  - Development of red-shifted mutants derived from luciferase of Brazilian click
      beetle Pyrearinus termitilluminans.
AB  - Luciferase, a bioluminescent protein, has been used as an analytical tool to
      visualize intracellular phenomena. Luciferase with red light emission is
      particularly useful for bioluminescence imaging because of its high transmittance
      in mammalian tissues. However, the luminescence intensity of existing luciferases
      with their emission over 600 nm is insufficient for imaging studies because of
      their weak intensities. We developed mutants of Emerald luciferase (Eluc) from
      Brazilian click beetle (Pyrearinus termitilluminans), which emits the strongest
      bioluminescence among beetle luciferases. We successively introduced four amino
      acid mutations into the luciferase based on a predicted structure of Eluc using
      homology modeling. Results showed that quadruple mutations
      R214K/H241K/S246H/H347A into the beetle luciferase emit luminescence with
      emission maximum at 626 nm, 88-nm red-shift from the wild-type luciferase. This
      mutant luciferase is anticipated for application in in vivo multicolor imaging in
      living samples.

PMID- 26313215
TI  - Modeling Plasma-to-Interstitium Glucose Kinetics from Multitracer Plasma and
      Microdialysis Data.
AB  - BACKGROUND: Quantitative assessment of the dynamic relationship between plasma
      and interstitial fluid (ISF) glucose and the estimation of the plasma-to-ISF
      delay are of major importance to determine the accuracy of subcutaneous glucose
      sensors, an essential component of open- and closed-loop therapeutic systems for
      type 1 diabetes mellitus (T1DM). The goal of this work is to develop a model of
      plasma-to-ISF glucose kinetics from multitracer plasma and interstitium data,
      obtained by microdialysis, in healthy and T1DM subjects, under fasting
      conditions. MATERIALS AND METHODS: A specific experimental design, combining
      administration of multiple tracers with the microdialysis technique, was used to
      simultaneously frequently collect plasma and ISF data. Linear time-invariant
      compartmental modeling was used to describe glucose kinetics from the tracer data
      because the system is in steady state. RESULTS: A two-compartment model was shown
      accurate and was identified from both plasma and ISF data. An "equilibration
      time" between plasma and ISF of 9.1 and 11.0 min (median) in healthy and T1DM
      subjects, respectively, was calculated. CONCLUSIONS: We have demonstrated that,
      in steady-state condition, the glucose plasma-to-ISF kinetics can be modeled with
      a linear two-compartment model and that the "equilibration time" between the two
      compartments can be estimated with precision. Future studies will assess plasma
      to-interstitium glucose kinetics during glucose and insulin perturbations in both
      healthy and T1DM subjects.

PMID- 26313216
TI  - Stable and Efficient Perovskite Solar Cells Based on Titania Nanotube Arrays.
AB  - Highly ordered 1D TiO2 nanotube arrays are fabricated and applied as
      nanocontainers and electron transporting material in CH3 NH3 PbI3 perovskite
      solar cells. The optimized device shows a power conversion efficiency of 14.8%,
      and improved stability under an illumination of 100 mW cm(-2). This is the best
      result based on 1D TiO2 nanostructures so far.

PMID- 26313218
TI  - Evaluation of Quality of Life Early and Late After Kidney Transplantation.
AB  - BACKGROUND The most important purpose of transplantation is to improve quality of
      life (QOL) together with increasing life expectancy. The aim of this study was to
      compare the QOL of both donors and kidney transplant recipients and a control
      group at the 3rd and 9th postoperative months by using the SF36 health survey, to
      investigate the changes in this 6-month period and to evaluate descriptive data
      and satisfaction of patients and donors. MATERIAL AND METHODS Forty-seven donors
      and 47 kidney transplant recipients who were operated on in Diyarbakir Gazi
      Yasargil Training and Research Hospital between August 2012 and March 2015 and
      had been followed up for at least 9 months and 47 healthy controls were enrolled
      in the study. RESULTS Physical functioning (PF) was higher at the 9th
      postoperative month compared to the 3rd month in the recipient group (p=0.028).
      Donors had higher PF (p=0.007) and functioning physical role (PR; p=0.01)
      compared to recipients. Recipients had lower PF (p=0.016), PR (p=0.004), and
      functional-emotional role (ER; p=0.03) at the 3rd month and had lower PR
      (p=0.002) at the 9th month postoperatively comparing to the control group. Donors
      had lower PF (p=0.007) and PR (p=0.01) at the 3rd month and had lower PR
      (p=0.035) at the 9th month postoperatively comparing to the control group. Donors
      and recipients had similar QOL at the 9th month. CONCLUSIONS During follow-up, we
      observed an increase in QOL (in some subgroups) at 9 months postoperatively.
      Donors and recipients had similar QOL (except for PR) with the control group at
      the 9th month. QOL was better in younger and male patients and educated persons.
      Donors did not show any regret regarding their donation. 

PMID- 26313220
TI  - Hypnosis for Awake Surgery of Low-grade Gliomas: Description of the Method and
      Psychological Assessment.
AB  - BACKGROUND: Awake craniotomy with intraoperative electric stimulation is a
      reliable method for extensive removal of low-grade gliomas while preserving the
      functional integrity of eloquent surrounding brain structures. Although fully
      awake procedures have been proposed, asleep-awake-asleep remains the standard
      technique. Anesthetic contraindications are the only limitation of this method,
      which is therefore not reliable for older patients with high-grade gliomas.
      OBJECTIVE: To describe and assess a novel method for awake craniotomy based on
      hypnosis. METHODS: We proposed a novel hypnosedation procedure to patients
      undergoing awake surgery for low-grade gliomas in our institution between May
      2011 and April 2015. Surgical data were retrospectively recorded. The subjective
      experience of hypnosis was assessed by 3 standardized questionnaires: the Cohen
      Perceived Stress Scale, the Posttraumatic Stress Disorder Checklist Scale, the
      Peritraumatic Dissociative Experience Questionnaire, and a fourth questionnaire
      designed specifically for this study. RESULTS: Twenty-eight questionnaires were
      retrieved from 43 procedures performed on 37 patients. The Peritraumatic
      Dissociative Experience Questionnaire revealed a dissociation state in 17 cases.
      The Perceived Stress Scale was pathological in 8 patients. Two patients in this
      group stated that they would not accept a second hypnosedation procedure. The
      Posttraumatic Stress Disorder Checklist Scale revealed 1 case of posttraumatic
      stress disorder. Burr hole and bone flap procedures were the most frequently
      reported unpleasant events during opening (15 of 52 events). CONCLUSION: The main
      findings of our study are the effectiveness of the technique, which in all cases
      allowed resection of the tumor up to functional boundaries, and the positive
      psychological impact of the technique in most of the patients.

PMID- 26313217
TI  - The case for an autoimmune aetiology of type 1 diabetes.
AB  - Type 1 diabetes (T1D) develops when there are insufficient insulin-producing beta
      cells to maintain glucose homeostasis. The prevailing view has been that T1D is
      caused by immune-mediated destruction of the pancreatic beta cells. However,
      several recent papers have challenged the long-standing paradigm describing T1D
      as a tissue-specific autoimmune disease. These authors have highlighted the gaps
      in our knowledge and understanding of the aetiology of T1D in humans. Here we
      review the evidence and argue the case for the autoimmune basis of human T1D. In
      particular, recent analysis of human islet-infiltrating T cells brings important
      new evidence to this question. Further data in support of the autoimmune basis of
      T1D from many fields, including genetics, experimental therapies and immunology,
      is discussed. Finally, we highlight some of the persistent questions relating to
      the pathogenesis of human type 1 diabetes that remain to be answered. 

PMID- 26313221
TI  - Neurodegeneration and Sport: Dated and Lacking Full Disclosure.

PMID- 26313222
TI  - Whole genome?

PMID- 26313223
TI  - Linking germline and somatic variation in Ewing sarcoma.
AB  - The identification of gene-regulatory polymorphisms that influence cancer
      susceptibility can identify key oncogenic pathways. A new study links a germline
      variant to Ewing sarcoma disease susceptibility and EWSR1-FLI1-mediated gene
      activation. 

PMID- 26313224
TI  - Genetic differential calculus.
AB  - High-throughput analysis of the phenotypes of mouse genetic knockouts presents
      several challenges, such as systematic measurement biases that can vary with
      time. A report from the EUMODIC consortium presents data from 320 genetic
      knockouts generated using standardized phenotyping pipelines and new statistical
      analyses aimed at increasing reproducibility across centers. 

PMID- 26313225
TI  - Building a staircase to precision medicine for biliary tract cancer.
AB  - A new study has conducted a comprehensive exome and transcriptome analysis of a
      large number of intrahepatic, perihilar and distal cholangiocarcinomas and
      gallbladder cancers in Japanese patients. This study identifies many new
      alterations, confirms genetic differences in these distinct subtypes of biliary
      tract cancer and demonstrates that approximately 40% of described genetic
      aberrations are potentially targetable. 

PMID- 26313226
TI  - Corrigendum: Transcriptional activation of retrotransposons alters the expression
      of adjacent genes in wheat.

PMID- 26313227
TI  - Corrigendum: Exploring population size changes using SNP frequency spectra.

PMID- 26313228
TI  - Patient satisfaction after orthodontic treatment combined with orthognathic
      surgery: A systematic review.
AB  - OBJECTIVE: To synthesize available evidence about factors associated with
      patients' satisfaction after orthodontic treatment combined with orthognathic
      surgery. MATERIALS AND METHODS: Studies that evaluated any factor associated with
      patients' satisfaction after the conclusion of an orthodontic treatment combined
      with an orthognathic surgery were identified. Orthognathic surgical procedures
      should have been undertaken after completion of craniofacial growth. Any
      satisfaction psychometric tool was considered. No language limitation was set. A
      detailed individual search strategy for each of the following bibliographic
      databases was crafted: MEDLINE, PubMed, EBM Reviews, Web of Science, EMBASE,
      LILACS, and Scopus. The references cited in the identified articles were also
      cross-checked, and a partial gray-literature search was undertaken using Google
      Scholar. RESULTS: Eight articles satisfied the inclusion criteria of this
      systematic review and accounted for 998 patients. The included studies showed
      large variation in sample size (range  =  44 to 505 patients), age (range  =  15
      to 72 years old), distinct psychological evaluation tools, and time elapsed
      between the assessment and the completion of surgery and postorthodontic
      treatment. Most of the studies (five of eight) were classified as having high
      risk of bias. CONCLUSION: Factors associated with satisfaction were final
      esthetic outcome, perceived social benefits from the outcome, type of
      orthognathic surgery, sex, and changes in patient self-concept during treatment.
      Factors associated with dissatisfaction were treatment length; sensation of
      functional impairment and/or dysfunction after surgery, and perceived omitted
      information about surgical risks.

PMID- 26313229
TI  - Phase Ib placebo-controlled, tissue biomarker trial of diindolylmethane (BR
      DIMNG) in patients with prostate cancer who are undergoing prostatectomy.
AB  - Epidemiologic, preclinical, and early phase I studies of the cruciferous
      vegetable bioactive metabolite, 3,3'-diindolylmethane (DIM), support its
      potential prostate cancer chemopreventive ability. We performed a multicenter,
      double-blind, placebo-controlled trial of DIM in patients diagnosed with prostate
      cancer and scheduled for radical prostatectomy. A total of 45 patients with organ
      confined prostate cancer were randomized to 21-28 days of an absorption-enhanced
      formulation of DIM (BR-DIM) at doses of 100 or 200 mg per os twice daily or to
      placebo twice daily. Prostate tissue levels of DIM were the primary endpoint,
      with selected secondary biomarker endpoints including blood levels of DIM, total
      prostate-specific antigen, testosterone, and the insulin-like growth factor-1:
      insulin-like growth factor binding protein-3 ratio and the urinary 2
      hydroxyestrone/16-hydroxyestrone ratio, obtained at baseline, at day 15, and
      before surgery, as well as tissue expression of androgen receptor, prostate
      specific antigen, Ki67, caspase 3 with cytochrome p450 mRNA expression and
      genotyping (polymorphisms). DIM was well tolerated with excellent study
      compliance and relatively rapid accrual of all 45 patients within 1 year. DIM
      levels were detected in only seven of 28 prostate tissue specimens. There was a
      statistically significant difference in the change in the urinary 2
      hydroxyestrone/16-hydroxyestrone ratio from baseline until before surgery between
      the placebo and 400 mg DIM groups, with otherwise statistically nonsignificant
      changes in plasma biomarker expression. The administration of BR-DIM to prostate
      cancer patients before prostatectomy yields detectable plasma levels but without
      consistent or significant tissue accumulation or biomarker modulation. This study
      demonstrates the feasibility of biologic evaluation of relatively nontoxic
      preventive agents in the preprostatectomy setting with the potential for rapid
      accrual.

PMID- 26313230
TI  - Fluoroscopic Views for a More Accurate Placement of Iliosacral Screws: An
      Experimental Study.
AB  - OBJECTIVES: Misperception on the fluoroscopic image showing a well-placed
      iliosacral (IS) screw can occur, when the screw is in reality misplaced. The
      purpose of this study was to demonstrate and highlight examples of misperception
      and suggest alternative inlet and outlet views to confirm adequate IS screw
      placement. METHODS: We used 9 different pelvic plastic models. In 8 of those
      models, IS screws were purposely misplaced: exiting anterior at the midportion of
      the S1 body, exiting at the lateral aspect of the anterior S1 body, abutting
      posterior to S1 body, exiting posterior to the S1 body, exiting superior to the
      far-side of the sacral ala, exiting superior to the S1 body, exiting partially in
      the S1 foramen, exiting completely in the S1 foramen. One model was used as
      control with correct screw placement. Different outlet and inlet views were
      tested to accurately detect important anatomic landmarks and avoid fake
      phenomenon (FP) using 3 different angles. RESULTS: Misperception occurred in 3
      models: (1) penetration at the midportion of the anterior border of S1, (2)
      penetration of the superior sacrum ala, and (3) partial penetration of S1
      foramen. In the first situation, misperception could be avoided when the
      "anterior inlet view" was obtained. In the other 2 situations, misperception
      could be avoided using specific outlet views herein described. CONCLUSIONS: Our
      findings highlight that misperception can occur using standard inlet and outlet
      views. We suggest using 2 variations of the inlet views and 3 variations of the
      outlet views to avoid misperception in clinical practice.

PMID- 26313231
TI  - Anatomic Ligament Repair Restores Ankle and Syndesmotic Rotational Stability as
      Much as Syndesmotic Screw Fixation.
AB  - OBJECTIVES: To compare the external rotation stability of 3 different syndesmotic
      stabilization techniques in a cadaveric ankle fracture model. METHODS:
      Nondestructive external rotation stresses of 4 N.m were applied to 8 cadaveric
      limbs using a hydraulic loading frame. Four conditions were tested using a
      repeated-measures design: intact and 3 repair conditions after a destabilizing
      ligamentous ankle injury with syndesmotic disruption. The 3 repair conditions
      were tricortical trans-syndesmotic screw fixation, posterior inferior
      tibiofibular ligament (PITFL) repair, and combined PITFL and deltoid ligament
      repair. External rotation of the ankle joint and syndesmosis was measured using a
      motion capture system and compared for each test condition. Repeated-measures 1
      way analyses of variance statistical tests were performed to compare the ankle
      and syndesmotic rotation findings between the 3 repair conditions and intact
      condition. RESULTS: Rotational ankle stability was not fully restored by any of
      the 3 repair constructs. The intact ankle joint externally rotated approximately
      half as many degrees as the 3 repair conditions (intact: 10.9; trans-syndesmotic
      screw: 17.0; PITFL: 21.4; and PITFL/deltoid: 15.6). The intact condition also
      demonstrated significantly fewer degrees of syndesmotic rotation than the repair
      constructs (intact 2.4; trans-syndesmotic screw 5.2; PITFL 8.5; and PITFL/deltoid
      6.9). Each of the repair conditions resulted in an externally rotated fibula when
      no loads were applied. The ligamentous repairs externally rotated the fibula
      twice as much as the trans-syndesmotic screw (P < 0.016). CONCLUSIONS: We found
      that combined repair of the PITFL and deltoid ligament restores an equivalent
      amount of ankle and syndesmotic rotational stability when compared to trans
      syndesmotic screw fixation. Based on our findings, ligamentous repair can
      potentially be a viable treatment alternative in unstable ankle fracture patients
      with syndesmotic disruption. LEVEL OF EVIDENCE: Therapeutic Level IV. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 26313232
TI  - Quantitative CT Scanning Analysis of Pure Ground-Glass Opacity Nodules Predicts
      Further CT Scanning Change.
AB  - BACKGROUND: We sought to determine whether quantitative analysis of lung
      adenocarcinoma manifesting as a ground-glass opacity (GGO) nodule (GGN) on
      initial CT scans can predict further CT scanning change or rate of growth.
      METHODS: This retrospective study included patients with lung adenocarcinoma
      manifesting as pure GGN on initial CT scans who were followed up with interval CT
      scanning until resection. All pure GGNs were classified based on CT scanning
      interval change in three subgroups as follows: group A (development of solid
      component), group B (growth of GGO component), and group C (no change in size).
      Nodule size, volume, density, mass, and CT scanning attenuation values were
      assessed from initial CT data sets. RESULTS: Fifty-four pure GGNs were enrolled
      and classified into group A (n = 9), group B (n = 25), and group C (n = 20).
      Nodule size, volume, mass, and density of the GGNs in each subgroup were not
      significantly different. The 97.5th percentile CT scanning attenuation value and
      slope of CT scanning attenuation values from the 2.5th to the 97.5th percentile
      were significantly different among the three subgroups (P = .02, P < .00). Three
      of nine (33%) pure GGNs showing a new solid component developed a solid component
      within 6 months. CONCLUSIONS: The 97.5th percentile CT scanning attenuation value
      and slope of CT scanning attenuation values from the 2.5th to the 97.5th
      percentile could be helpful in predicting future CT scanning change and growth
      rate of pure GGNs. Pure GGNs showing higher 97.5th percentile CT scanning
      attenuation values and steeper slopes of CT scanning attenuation values may
      require more frequent follow-up than the usual interval of 6 months.

PMID- 26313234
TI  - The use of the trendelenburg position in the surgical treatment of extreme
      cerebellar slump.
AB  - BACKGROUND: State-of-the-art treatment for Chiari Malformation I (CM-I) consists
      of decompression by posterior fossa craniectomy. A rare but severe complication
      that develops over months to years after this procedure is cerebellar slump.
      Treatment options for this condition are limited. We present a new and promising
      approach to treat this rare condition. METHODS: The patients were placed in the
      Trendelenburg position to facilitate ascent of the cerebellum. After almost
      complete dissolution of neurologic symptoms, surgical reconstruction was
      performed by tonsillar resection and the creation of a new structural support
      using a bone graft. RESULTS: Both patients experienced good clinical and
      morphological outcomes immediately after surgery, and for two years thereafter.
      CONCLUSIONS: Neurological symptoms related to cerebellar or brainstem slump can
      be adequately reversed by placing the patient in the Trendelenburg position.
      After uneventful gravitational reversal of the slump, safe surgical
      reconstruction of the cerebellar support can be performed to securely preserve
      the anatomical reversal.

PMID- 26313233
TI  - Dynamics of H3K27me3 methylation and demethylation in plant development.
AB  - Epigenetic regulation controls multiple aspects of the plant development. The N
      terminal tail of histone can be differently modified to regulate various
      chromatin activities. One of them, the trimethylation of histone H3 lysine 27
      (H3K27me3) confers a repressive chromatin state with gene silencing. H3K27me3 is
      dynamically deposited and removed throughout development. While components of the
      H3K27me3 writer, Polycomb repressive complex 2 (PRC2), have been reported for
      almost 2 decades, it is only recently that JUMONJI (JMJ) proteins are reported as
      H3K27me3 demethylases, affirming the dynamic nature of histone modifications.
      This review highlights recent progress in plant epigenetic research, focusing on
      the H3K27me3 demethylases. 

PMID- 26313235
TI  - Longitudinal Changes in Body Fat and Its Distribution in Relation to
      Cardiometabolic Risk in Black South African Women.
AB  - BACKGROUND: Ethnic differences in body composition and cardiometabolic risk have
      been reported in cross-sectional studies. This study aimed to investigate changes
      in body composition over 5.5 years, and its association with cardiometabolic risk
      in premenopausal black South African (SA) women. METHODS: Changes in body
      composition and body fat distribution (dual-energy x-ray absorptiometry and
      computerized tomography), fasting glucose, insulin, and lipid concentrations,
      were measured in 63 black SA women at baseline (age: 27 +/- 8 years), and 5.5
      years later. RESULTS: Body weight and fat mass (FM) increased by 6.9 +/- 9.9 kg
      and 4.3 +/- 6.9 kg, respectively, over the 5.5 years with a relative (%FM)
      increase in central and decrease in peripheral FM (all P < 0.05). Fasting glucose
      and lipid concentrations (except HDL-cholesterol) increased over the follow-up
      period (all P < 0.05). Both baseline and changes in body fat distribution were
      associated with cardiometabolic risk. Independent of baseline age, FM and insulin
      sensitivity, baseline trunk:leg was associated with reduced insulin sensitivity
      at follow-up (Matsuda index; beta = -0.41, P = 0.002). Increasing trunk:gynoid
      ratio was associated with higher plasma insulin levels (beta = 0.31, P = 0.023)
      and reduced insulin sensitivity (Matsuda index; beta = -0.52, P < 0.001) at
      follow-up. CONCLUSIONS: Weight gain in free-living black SA women over 5.5 years
      was associated with a centralization of fat mass, which predicted an increase in
      cardiometabolic risk.

PMID- 26313236
TI  - Estimated daily intake and health risk of heavy metals by consumption of milk.
AB  - Cd, Co, Pb, Cu and Ni were analysed in 480 milk samples by flame atomic
      absorption spectrophotometry. Mean concentrations were 0.001, 0.061, 0.014, 0.738
      and 0.028 mg/kg, respectively. Mean concentration of Cd was very low, whereas Cu
      exceeded the maximum limits established by the Codex Alimentarius. In some areas,
      the Pb concentration exceeded the maximum limit as set by the Codex Alimentarius.
      The highest estimated daily intake (EDI) of Cu calculated for male infants (1-3
      year) was 33.534 ug/kg bw/day, while the lowest EDI was recorded for Cd (0.004
      ug/kg bw/day) in adult females above 16 years. The results suggested that Cu and
      Pb from milk in the investigated areas may pose a health risk to the consumers. 

PMID- 26313237
TI  - Learning to prescribe in a student-run clinic.

PMID- 26313238
TI  - Molecular modeling, in silico screening and molecular dynamics of PfPRL-PTP of P.
      falciparum for identification of potential anti-malarials.
AB  - Millions of deaths occur every year due to malaria. Growing resistance against
      existing drugs for treatment of malaria has exaggerated the problem further.
      There is an intense demand of identifying drug targets in malaria parasite. PfPRL
      PTP protein is PRL group of phosphatase, and one of the interesting drug targets
      being involved in three important pathways of malaria parasite (secretion,
      phosphorylation, and prenylation). Therefore, in this study, we have modeled
      three-dimensional structure of PfPRL-PTP followed by validation of 3D structure
      using RAMPAGE, verify3D, and other structure validation tools. We could identify
      12 potential inhibitory compounds using in silico screening of NCI library
      against PfPRL-PTP with Glide. The molecular dynamics simulation was also
      performed using GROMACS on PfPRL-PTP model alone and PfPRL-PTP-inhibitor complex.
      This study of identifying potential drug-like molecules would add up to the
      process of drug discovery against malaria parasite. 

PMID- 26313240
TI  - Association of the functional SNP rs2275294 in ZNF512B with risk of amyotrophic
      lateral sclerosis and Parkinson's disease in Han Chinese.
AB  - The single nucleotide polymorphism (SNP) rs2275294 of the ZNF512B gene has been
      reported to be associated with a risk of ALS in the Japanese population. Here we
      conducted a case-control study examining the possible association of rs2275294
      with risk of sporadic ALS and PD in Han Chinese. Our study included 301 patients
      with ALS and 457 age- and gender-matched controls, as well as 555 patients with
      PD and 473 age- and gender-matched controls. Subjects were genotyped at rs2275293
      using the ligase detection reaction. The genotype distribution of rs2275294 shows
      significant difference between patients with ALS and the control group according
      to the dominant model (OR 1.518, 95% CI 1.074-2.145, p = 0.018) and based on
      alleles (OR 1.249, 95% 1.016-1.534, p = 0.035). Stratification analysis showed a
      significant difference between females with ALS and female controls based on the
      dominant model (OR 3.285, 95% CI 1.856-5.815, p < 0.001) or alleles (OR 1.697,
      95% CI 1.208-2.383, p = 0.002). In contrast, no significant differences were
      identified between rs2275294 and patients with PD. In conclusion, our case
      control study suggests that the CC genotype and C allele at rs2275294 are
      associated with increased risk of ALS in Han Chinese, particularly females. 

PMID- 26313241
TI  - Are asthma patients at increased risk of clinical depression? A longitudinal
      cohort study.
AB  - OBJECTIVE: In this study, we assessed whether adult patients with asthma are more
      likely to be diagnosed with depression than diabetes patients or "healthy"
      controls during follow-up in primary care. METHODS: Data from the Nijmegen
      Continuous Morbidity Registration were used to assess the risk for a first
      depression. Patients with asthma were compared with patients with diabetes and
      with two healthy controls matched on age, gender, socioeconomic status and
      attending general practice. With Cox proportional hazard analysis, we compared
      the risk of depression between these groups. These analyses were corrected for
      relevant covariates including a time-depending variable for multimorbidity.
      Explorative subgroup analyses were done for age, gender, socioeconomic status and
      multimorbidity. RESULTS: Cumulative incidence of depression in asthma patients
      was 5.2%, in DM patients 4.1% and in control subjects 3.3%. The hazard ratios for
      a first episode of depression in the asthma patients (n = 795) compared to DM
      patients (n = 1033) and control subjects after correction for covariates were
      1.11 (95% CI 0.60-2.04) and 1.18 (95% CI 0.78-1.79), respectively. Exploratory
      analyses showed that asthma patients without multimorbidity were at higher risk
      for a depression compared to reference groups, while asthma patients with
      multimorbidity were at lower risk for depression. CONCLUSION: Asthma patients
      were not more likely to be diagnosed with a first depression compared to
      "healthy" control subjects or diabetes patients. The influence of multimorbidity
      on depression risk in asthma patients warrants further study.

PMID- 26313242
TI  - Transferable force fields for adsorption of small gases in zeolites.
AB  - We provide transferable force fields for oxygen, nitrogen, and carbon monoxide
      that are able to reproduce experimental adsorption in both pure silica and
      alumino-substituted zeolites at cryogenic and high temperatures. The force field
      parameters can be combined with those previously reported for carbon dioxide,
      methane, and argon, opening the possibility for studying mixtures of interest
      containing the six components. Using these force field parameters we obtained
      some adsorption isotherms at cryogenic temperatures that at first sight were in
      discrepancies with experimental values for certain molecules and structures. We
      attribute these discrepancies to the sensitiveness of the equipment and to
      kinetic impedimenta that can lead to erratic results. Additional problems can be
      found during simulations when extra-framework cations are present in the system
      as their lack of mobility at low temperatures could lead to kinetic effects that
      hinder experimental adsorption. 

PMID- 26313239
TI  - Effect of vaccine administration modality on immunogenicity and efficacy.
AB  - The many factors impacting the efficacy of a vaccine can be broadly divided into
      three categories: features of the vaccine itself, including immunogen design,
      vaccine type, formulation, adjuvant and dosing; individual variations among
      vaccine recipients and vaccine administration-related parameters. While much
      literature exists related to vaccines, and recently systems biology has started
      to dissect the impact of individual subject variation on vaccine efficacy, few
      studies have focused on the role of vaccine administration-related parameters on
      vaccine efficacy. Parenteral and mucosal vaccinations are traditional approaches
      for licensed vaccines; novel vaccine delivery approaches, including needless
      injection and adjuvant formulations, are being developed to further improve
      vaccine safety and efficacy. This review provides a brief summary of vaccine
      administration-related factors, including vaccination approach, delivery route
      and method of administration, to gain a better understanding of their potential
      impact on the safety and immunogenicity of candidate vaccines. 

PMID- 26313243
TI  - Hypoxic preconditioning promotes the translocation of protein kinase C epsilon
      binding with caveolin-3 at cell membrane not mitochondrial in rat heart.
AB  - Protein kinase C has been shown to play a central role in the cardioprotection of
      ischemic preconditioning. However, the mechanism underlying PKC-mediated
      cardioprotection is not completely understood. Given that caveolae are critical
      for PKC signaling, we sought to determine whether hypoxic preconditioning
      promotes translocation and association of PKC isoforms with caveolin-3. A
      cellular model of hypoxic preconditioning from adult rat cardiac myocytes (ARCM)
      or H9c2 cells was employed to examine PKC isoforms by molecular, biochemical and
      cellular imaging analysis. Hypoxia was induced by incubating the cells in an
      airtight chamber in which O2 was replaced by N2 with glucose-free Tyrode's
      solution. Cells were subjected to hypoxic preconditioning with 10 minutes of
      hypoxia followed by 30 minutes of reoxygenation. Western blot data indicated that
      the band intensity for PKCepsilon, PKCdelta or PKCalpha, but not PKCbeta and
      PKCzeta was enhanced significantly by hypoxic preconditioning from the caveolin
      enriched plasma membrane interactions. Immunoprecipitation experiments from the
      caveolin-enriched membrane fractions of ARCM showed that the level of PKCepsilon,
      PKCdelta and PKCalpha in the anti-caveolin-3 immunoprecipitates was also
      increased by hypoxic preconditioning. Further, our FRET analysis in H9c2 cells
      suggested that there is a minimum FRET signal for caveolin-3 and PKCepsilon along
      cell peripherals, but hypoxic preconditioning enhanced the FRET signal,
      indicating a potential interaction between caveolin-3 and PKCepsilon. And also
      treatment of the cells with hypoxic preconditioning led to a smaller amount of
      translocation of PKCepsilon to the mitochondria than that to the membrane. We
      demonstrate that hypoxic preconditioning promotes rapid association of
      PKCepsilon, PKCdelta and PKCalpha with the caveolin-enriched plasma membrane
      microdomain of cardiac myocytes, and PKCepsilon via direct molecular interaction
      with caveolin-3. This regulatory mechanism may play an important role in
      cardioprotection. 

PMID- 26313244
TI  - MRI evidence of persistent joint inflammation and progressive joint damage
      despite clinical remission during treatment of early rheumatoid arthritis.
AB  - OBJECTIVES: To determine the value of magnetic resonance imaging (MRI) of bones
      and joints in patients with recent-onset rheumatoid arthritis (RA) treated for 2
      years from diagnosis with disease-modifying anti-rheumatic drugs (DMARDs) and
      glucocorticoids. METHOD: Thirteen patients with early RA were treated according
      to clinical practice and followed with MRI, radiographs, and Disease Activity
      Score calculated on 28 joints (DAS28) at inclusion (baseline) and after 1, 4, 7,
      13, and 25 months. MRI of the dominant wrist and metacarpophalangeal (MCP) joints
      were assessed for synovitis, bone oedema, and erosions using the RA MRI Score
      (RAMRIS) and for tenosynovitis by an MRI tenosynovitis scoring method.
      Radiographs were assessed by the van der Heijde modified Sharp score (SHS).
      Clinical remission was defined by a DAS28 < 2.6. RESULTS: MRI at baseline
      detected inflammation in joints and tendons in all patients as well as erosions
      in 10 out of 13 patients. Over time, the erosion score increased while the
      synovitis and tenosynovitis scores remained almost unchanged. Bone oedema
      strongly correlated with synovitis. Synovitis and tenosynovitis correlated well
      with the erosion score at baseline but not thereafter. The MRI changes showed
      that joint damage started early and continued in the presence of persistent
      synovial and tenosynovial inflammation. CONCLUSIONS: The observations made in
      this small study suggest that the treatment goal of 'clinical remission' should
      be supplemented by a 'joint remission' goal. To this end, MRI is an appropriate
      tool. Further studies are needed to evaluate the optimal use of MRI in early RA.

PMID- 26313245
TI  - Immunosuppressants for the prophylaxis of corneal graft rejection after
      penetrating keratoplasty.
AB  - BACKGROUND: Penetrating keratoplasty is a corneal transplantation procedure in
      which a full-thickness cornea from the host is replaced by a graft from a donor.
      The use of various immunosuppressants to prevent graft rejection, the most common
      cause of graft failure in the late postoperative period, is increasing.
      OBJECTIVES: To assess the effectiveness of immunosuppressants in the prophylaxis
      of corneal allograft rejection after high- and normal-risk keratoplasty. SEARCH
      METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group
      Trials Register) (2015, Issue 4), Ovid MEDLINE, Ovid MEDLINE In-Process and Other
      Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to May
      2015), EMBASE (January 1980 to May 2015), China National Knowledge Infrastructure
      (CNKI) (January 1913 to February 2015), VIP database (January 1989 to February
      2015), Wanfang Data (www.wanfangdata.com) (January 1990 to February 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 English language databases on 18 May 2015 and the Chinese
      language databases on 20 February 2015. SELECTION CRITERIA: We included all
      randomised controlled trials (RCTs) assessing the use of immunosuppressants in
      the prevention of graft rejection, irrespective of publication language. DATA
      COLLECTION AND ANALYSIS: We used standard procedures expected by Cochrane. The
      primary outcome was clear graft survival at 12 months after penetrating
      keratoplasty. Secondary outcomes included graft rejection, best-corrected visual
      acuity, and quality of life. We defined 'high-risk keratoplasty' as repeat
      keratoplasty and other indications of reduced graft survival. MAIN RESULTS: We
      included six studies conducted in Germany (three studies), Iran, India, and
      China. Three studies were conducted in people undergoing high-risk keratoplasty
      and investigated three different comparisons: systemic mycophenolate mofetil
      (MMF) versus no MMF; systemic MMF versus systemic cyclosporine A (CsA); and
      topical CsA versus placebo. One study compared topical tacrolimus to topical
      steroid in people with normal-risk keratoplasty, and two studies compared topical
      CsA to placebo in people experiencing graft rejection after normal-risk
      keratoplasty. Overall, we considered the trials to be at unclear or high risk of
      bias.MMF may not improve clear graft survival (risk ratio (RR) 1.06, 95%
      confidence interval (CI) 0.84 to 1.33, 1 RCT, 87 participants, low-quality
      evidence) but may reduce the risk of graft rejection (RR 0.49, 95% CI 0.22 to
      1.08, 1 RCT, 87 participants, low-quality evidence) compared to no MMF. Visual
      acuity was not reported.In 1 study of 52 people comparing systemic MMF and
      systemic CsA, there were no graft failures in the first year of follow-up. Data
      from the longest follow-up (three years) suggest that there may be little
      difference in the effect of these two treatments on clear graft survival (RR
      1.10, 95% CI 0.90 to 1.35, low-quality evidence). There was low-quality evidence
      of an increased risk of graft rejection with systemic MMF compared to systemic
      CsA, but with wide CIs compatible with increased risk with systemic CsA (RR 1.48,
      95% CI 0.56 to 3.93, low-quality evidence). Visual acuity was not reported.One
      study of 84 people comparing topical CsA to placebo did not report clear graft
      survival at 1 year, which suggests that all grafts survived to 1 year. This study
      suggests that the use of topical CsA probably leads to little or no difference in
      graft rejection (RR 1.00, 95% CI 0.39 to 2.58, moderate-quality evidence). At one
      year, the mean difference (MD) between the two groups in visual acuity was 0.07
      (95% CI -0.01 to 0.15, moderate-quality evidence).Topical CsA probably does not
      have an effect on clear graft survival in people experiencing graft rejection
      after normal-risk keratoplasty compared to placebo (RR 1.03, 95% CI 0.96 to 1.10,
      2 RCTs, 283 participants, moderate-quality evidence). There were inconsistent
      findings on graft rejection, with one study reporting a reduced incidence of
      graft rejection in the CsA group (RR 0.35, 95% CI 0.14 to 0.87, 230 participants)
      but the other study reporting a higher average number of episodes of graft
      rejection in people treated with CsA (MD 1.30, 95% CI 0.39 to 2.21, 43
      participants). Overall, we judged this to be low-quality evidence due to risk of
      bias and inconsistency. There was no evidence for a difference in visual acuity
      between the 2 groups at final follow-up (approximately 18 months, range 2 to 33
      months) (MD 0.04, 95% CI -0.10 to 0.18, 1 RCT, 43 participants, low-quality
      evidence).In 1 study comparing topical tacrolimus to topical steroid, the graft
      survived in all of the 12 treated participants and 20 control participants at 6
      months. Graft rejection was rare (0 out of 12 versus 2 out of 20) (RR 0.32, 95%
      CI 0.02 to 6.21, low-quality evidence). Visual acuity was not reported.None of
      the studies reported on quality of life. We identified an unpublished trial of
      basiliximab (Simulect) (NCT00409656), probably completed in 2005. AUTHORS'
      CONCLUSIONS: Current evidence on the effect of immunosuppressants in the
      prevention of graft failure and rejection after high- and normal-risk
      keratoplasty is largely low quality because the number of trials was limited,
      and, in general, the trials were small and at risk of bias. Future trials should
      be large enough to detect important clinical effects, conducted with a view to
      minimising the risk of bias, and they should measure outcomes important to
      patients.

PMID- 26313246
TI  - Coatings comprising chitosan and Mentha piperita L. or Mentha * villosa Huds
      essential oils to prevent common postharvest mold infections and maintain the
      quality of cherry tomato fruit.
AB  - In this study, we evaluated the efficacy of coatings comprising shrimp chitosan
      (CHI) and Mentha piperita L. (MPEO) or Mentha * villosa Huds (MVEO) essential
      oils to control mold infections caused by Aspergillus niger, Botrytis cinerea,
      Penicillium expansum and Rhizopus stolonifer in cherry tomato fruits (Solanum
      lycopersicum L.) during storage at room temperature (25 degrees C for 12 days)
      and low temperature (12 degrees C for 24 days). The effects of the coatings on
      the physicochemical and sensory characteristics of cherry tomato fruits during
      storage were also assessed. The minimum inhibitory concentration (MIC) of CHI
      against all test fungi was 8 mg/mL, whereas the MIC for both MPEO and MVEO was 5
      MUL/mL. Combinations of CHI at 4 mg/mL and MPEO or MVEO at 2.5 or 1.25 MUL/mL
      strongly inhibited the mycelial growth and spore germination of target fungi. The
      coatings comprising CHI and MPEO or CHI and MVEO at the different tested
      concentrations delayed the growth of decay-causing fungi in artificially
      contaminated tomato fruit during storage at either room temperature or low
      temperature. The assayed coatings preserved the quality of cherry tomato fruit
      during storage, in terms of physicochemical and sensory attributes. These results
      indicate that coatings comprising CHI and MPEO or CHI and MVEO represent
      promising postharvest treatments to prevent common postharvest mold infections in
      cherry tomato fruit during storage without affecting the quality of the fruit.

PMID- 26313247
TI  - Race, law, and health: Examination of 'Stand Your Ground' and defendant
      convictions in Florida.
AB  - Previous analyses of Stand Your Ground (SYG) cases have been primarily
      descriptive. We examine the relationship between race of the victim and
      conviction of the defendant in SYG cases in Florida from 2005 to 2013. Using a
      regression analytic approach, we allow for simultaneous examination of multiple
      factors to better understand existing interrelationships. Data was obtained from
      the Tampa Bay Times SYG database (237 cases) which was supplemented with
      available online court documents and/or news reports. After excluding cases which
      were, still pending as of January 2015; had multiple outcomes (because of
      multiple suspects); and missing information on race of victim and weapon of
      victim, our final analytic sample has 204 cases. We chose whether the case
      resulted in a conviction as the outcome. We develop logistic regression models
      using significant bivariate predictors as candidates. These include race of the
      victim (White, non-White), whether the defendant could have retreated from the
      situation, whether the defendant pursued the victim, if the victim was unarmed,
      and who was the initiator of the confrontation. We find race of the victim to be
      a significant predictor of case outcome in this data set. After controlling for
      other variables, the defendant is two times (OR = 2.1, 95% CI [1.07, 4.10]) more
      likely to be convicted in a case that involves White victims compared to those
      involving non-White victims. Our results depict a disturbing message: SYG
      legislation in Florida has a quantifiable racial bias that reveals a leniency in
      convictions if the victim is non-White, which provides evidence towards unequal
      treatment under the law. Rather than attempting to hide the outcomes of these
      laws, as was done in Florida, other states with SYG laws should carry out similar
      analyses to see if their manifestations are the same as those in Florida, and all
      should remediate any injustices found. 

PMID- 26313248
TI  - Cycle-dependent in vitro wear performance of dental ceramics after clinical
      surface treatments.
AB  - AIM: To investigate the two-body wear performance of dental ceramics after
      different clinical surface treatments as a function of number of wear cycles.
      MATERIAL AND METHODS: Standardized specimens (n=72/material) were prepared from
      two different zirconia ceramics, a veneering porcelain, and a lithiumdisilicate
      glass ceramic. Specimens were progressively glazed, ground, and polished. After
      each treatment step 24 specimens per material were kept at the obtained surface
      state. Steatite and human enamel specimens served as reference materials. Two
      body wear tests were performed with steatite spheres as antagonists in a pin-on
      block design (50N, 1.6 Hz, lateral movement: 1mm, mouth opening: 2mm) under
      simultaneous thermal cycling (5/55  degrees C, 2 min/cycle). For investigating
      the dynamic evolution of the wear process, 9 groups per material (n=8/group) were
      defined, differing in surface state (glazed, ground, and polished) and number of
      chewing cycles (40T, 80T, and 120T; T: *1000): glazed 40T, glazed 80T, glazed
      120T, ground 40T, ground 80T, ground 120T, polished 40T, polished 80T, polished
      120T. Surface roughness, wear depth of the specimens and relative wear area of
      the steatite antagonists were determined using an optical 3D laser scanning
      microscope. SEM evaluation was done. Mean values and standard deviations were
      calculated and statistically analyzed (one-way ANOVA, post-hoc Bonferroni,
      alpha=0.05). RESULTS: Veneering and lithiumdisilicate ceramics showed higher wear
      depths than zirconia ceramics (p<0.05). Wear of veneering and lithiumdisilicate
      ceramics and their antagonists increased with wear cycles but was only marginally
      influenced by the initial surface state. Wear of zirconia was not influenced by
      wear cycles but antagonists of zirconia showed a cycle-dependent wear increase.
      Polished zirconia surfaces showed lowest wear for material and antagonist. Wear
      mechanism of common ceramics was characterized by abrasive wear. Zirconia in
      contrast showed a superficial cyclic shifting of worn material of the antagonist.
      CONCLUSIONS: Wear of zirconia and standard ceramics showed different wear
      performances, strongly influenced by surface treatments as well as number of wear
      cycles.

PMID- 26313249
TI  - Mechanical and thermal properties of conventional and microcellular injection
      molded poly (lactic acid)/poly (epsilon-caprolactone) blends.
AB  - In view of their complementary properties, blending polylactide (PLA) with poly
      (epsilon-caprolactone) (PCL) becomes a good choice to improve PLA's properties
      without compromising its biodegradability. A series of blends of biodegradable
      PLA and PCL with different mass fraction were prepared by melt mixing. Standard
      tensile bars were produced by both conventional and microcellular injection
      molding to study their mechanical and thermal properties. With the increase in
      PCL content, the blend showed decreased tensile strength and modulus; however,
      elongation was dramatically increased. With the addition of PCL, the failure mode
      changed from brittle fracture of the neat PLA to ductile fracture of the blend as
      demonstrated by tensile test. Various theoretical models based on dispersion and
      interface adhesion were used to predict the Young's modulus and the results shows
      the experimental data are consistent with the predictions of the foam model and
      Kerner-Uemura-Takayangi model. The thermal behavior of the blends was
      investigated by DSC and TGA. The melting temperature and the degree of
      crystallinity of PCL in the PLA/PCL did not significantly change with the PCL
      content increasing in the whole range of blends composition. 

PMID- 26313250
TI  - Accurate (13)C and (15)N Chemical Shift and (14)N Quadrupolar Coupling Constant
      Calculations in Amino Acid Crystals:  Zwitterionic, Hydrogen-Bonded Systems.
AB  - EIM (embedded ion method), cluster, combined EIM/cluster, and isolated molecule
      (13)C and (15)N chemical shielding and quadrupolar coupling constant (QCC)
      calculations at the B3LYP level with D95**, D95++**, 6-311G**, and 6-311+G**
      basis sets were done on the amino acids l-alanine, l-asparagine monohydrate, and
      l-histidine monohydrate monohydrochloride and on the two polymorphs alpha and
      gamma glycine. The intermolecular interactions that are present in the amino acid
      crystals are accounted for in the EIM calculations by a finite array of point
      charges calculated from Ewald lattice sums and in the cluster calculations by a
      shell of neighboring molecules or molecular fragments. The combined EIM/cluster
      calculations utilize a cluster of molecules inside an EIM point charge array. The
      theoretical (13)C and (15)N principal shielding values for the amino acids
      studied are compared to the experimental principal shift values. In addition,
      theoretical CN bond orientations in the chemical shift principal axis system
      (PAS) are compared to the experimental orientations obtained from (13)C-(14)N
      dipolar couplings. The theoretical QCC at the nitrogen positions are compared to
      experimental (14)N QCC principal values reported in the literature. The carbon
      and nitrogen theoretical chemical shielding, the C-N orientations, and the QCCs
      from the ab initio calculations show improved agreement with the experimental
      values when the intermolecular interactions are accounted for by EIM or cluster
      calculations. The EIM (13)C shielding calculations are found to give better
      agreement with the experimental values than cluster (13)C shielding calculations.
      However, to achieve good agreement between the theoretical (14)N QCC and the
      (15)N principal shielding values with the respective experimental values, both
      intermolecular electrostatic and covalent interactions have to be included
      explicitly in the EIM/cluster calculations. 

PMID- 26313251
TI  - Electrochemical Behavior of Sodium Anions.
AB  - Electrochemical studies of sodium and its salts were carried out in 0.1 M TBAP
      and in electrolyte-free tetrahydrofuran solutions at room temperature. Working
      electrodes employed in these studies were platinum and mercury film
      ultramicroelectrodes, as well as a sodium electrode. The electrochemical
      reduction of sodium salts in 0.1 M TBAP/THF solutions leads to deposition of
      sodium on the platinum surface, and at more negative potentials, a stripping wave
      attributed to formation of the sodium anion is observed; the oxidation wave for
      the sodium anion is not observed. Possible mechanisms for the removal of the
      anion by competing processes are discussed. The results obtained from
      electrochemical studies of sodium electrodes and of sodium salts at a mercury
      film electrode are presented. 

PMID- 26313252
TI  - Discovery and Evaluation of Clinical Candidate AZD3759, a Potent, Oral Active,
      Central Nervous System-Penetrant, Epidermal Growth Factor Receptor Tyrosine
      Kinase Inhibitor.
AB  - Recent reports suggest that an increasing number of patients with lung cancer,
      especially those with activating mutations of the epidermal growth factor
      receptor (EGFR), also present with brain metastases and leptomeningeal
      metastases. These patients have poor prognosis as there are no approved drugs for
      these indications. Available agents have poor efficacy for these patients even at
      well above their standard dose. Herein, we report the discovery of (4-[(3-chloro
      2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl (2R)-2,4-dimethylpiperazine-1
      carboxylate 1m (AZD3759), an investigational drug currently in Phase 1 clinical
      trial, which has excellent central nervous system penetration and which induces
      profound regression of brain metastases in a mouse model. 

PMID- 26313253
TI  - Reverse Kebab Structure Formed inside Carbon Nanofibers via Nanochannel Flow.
AB  - The morphology of polymers inside a confined space has raised great interest in
      recent years. However, polymer crystallization within a one-dimensional carbon
      nanostructure is challenging due to the difficulty of polar solvents carrying
      polymers to enter a nonpolar graphitic nanotube in bulk solution at normal
      temperature and pressure. Here we describe a method whereby nylon-11 was
      crystallized and periodically distributed on the individual graphitic nanocone
      structure within hollow carbon nanofibers (CNF). Differential scanning
      calorimetry and X-ray diffraction indicate that the nylon polymer is in the
      crystalline phase. A mechanism is suggested for the initiation of nanochannel
      flow in a bulk solvent as a prerequisite condition to achieve interior polymer
      crystallization. Selective etching of polymer crystals on the outer wall of CNF
      indicates that both surface tension and viscosity affect the flow within the CNF.
      This approach provides an opportunity for the interior functionalization of
      carbon nanotubes and nanofibers for applications in the biomedical, energy, and
      related fields. 

PMID- 26313254
TI  - SERS Nanoparticles in Medicine: From Label-Free Detection to Spectroscopic
      Tagging.

PMID- 26313255
TI  - Iron-catalyzed cross coupling of P-H/C-O bonds: efficient synthesis of alpha
      alkoxyphosphorus compounds.
AB  - An efficient P-C bond-formation through iron-catalyzed cross coupling of P-H/C-O
      bonds is developed for the first time. This reaction proceeds efficiently to
      produce the corresponding valuable alpha-alkoxyphosphorus compounds under mild
      conditions with a wide generality. 

PMID- 26313256
TI  - Normal and Extreme Wind Conditions for Power at Coastal Locations in China.
AB  - In this paper, the normal and extreme wind conditions for power at 12 coastal
      locations along China's coastline were investigated. For this purpose, the daily
      meteorological data measured at the standard 10-m height above ground for periods
      of 40-62 years are statistically analyzed. The East Asian Monsoon that affects
      almost China's entire coastal region is considered as the leading factor
      determining wind energy resources. For most stations, the mean wind speed is
      higher in winter and lower in summer. Meanwhile, the wind direction analysis
      indicates that the prevalent winds in summer are southerly, while those in winter
      are northerly. The air densities at different coastal locations differ
      significantly, resulting in the difference in wind power density. The Weibull and
      lognormal distributions are applied to fit the yearly wind speeds. The lognormal
      distribution performs better than the Weibull distribution at 8 coastal stations
      according to two judgement criteria, the Kolmogorov-Smirnov test and absolute
      error (AE). Regarding the annual maximum extreme wind speed, the generalized
      extreme value (GEV) distribution performs better than the commonly-used Gumbel
      distribution. At these southeastern coastal locations, strong winds usually occur
      in typhoon season. These 4 coastal provinces, that is, Guangdong, Fujian, Hainan,
      and Zhejiang, which have abundant wind resources, are also prone to typhoon
      disasters. 

PMID- 26313257
TI  - Prospection and Evaluation of (Hemi) Cellulolytic Enzymes Using Untreated and
      Pretreated Biomasses in Two Argentinean Native Termites.
AB  - Saccharum officinarum bagasse (common name: sugarcane bagasse) and Pennisetum
      purpureum (also known as Napier grass) are among the most promising feedstocks
      for bioethanol production in Argentina and Brazil. In this study, both biomasses
      were assessed before and after acid pretreatment and following hydrolysis with
      Nasutitermes aquilinus and Cortaritermes fulviceps termite gut digestome. The
      chemical composition analysis of the biomasses after diluted acid pretreatment
      showed that the hemicellulose fraction was partially removed. The (hemi)
      cellulolytic activities were evaluated in bacterial culture supernatants of
      termite gut homogenates grown in treated and untreated biomasses. In all cases,
      we detected significantly higher endoglucanase and xylanase activities using
      pretreated biomasses compared to untreated biomasses, carboxymethylcellulose and
      xylan. Several protein bands with (hemi) cellulolytic activity were detected in
      zymograms and two-dimensional gel electrophoresis. Some proteins of these bands
      or spots were identified as xylanolytic peptides by mass spectrometry. Finally,
      the diversity of cultured cellulolytic bacterial endosymbionts associated to both
      Argentinean native termite species was analyzed. This study describes, for the
      first time, bacterial endosymbionts and endogenous (hemi) cellulases of two
      Argentinean native termites as well as their potential application in degradation
      of lignocellulosic biomass for bioethanol production. 

PMID- 26313259
TI  - Correction: The Role of High Mobility Group Box 1 Protein (HMGB1) in the
      Immunopathology of Experimental Pulmonary Tuberculosis.

PMID- 26313258
TI  - Nutritional Supplementation Is a Necessary Complement to Dietary Counseling among
      Tuberculosis and Tuberculosis-HIV Patients.
AB  - The Brazilian Ministry of Health and the World Health Organization recommend
      dietary counseling for patients with malnutrition during tuberculosis treatment.
      Patients under tuberculosis therapy (infected and not infected with HIV) were
      followed-up to evaluate the effectiveness of dietary counseling. OBJECTIVE:
      describe the nutritional status of patients with tuberculosis. METHODS: an
      observational follow-up study over a 180-day period of tuberculosis therapy in
      adults was conducted. Subjects were assessed for body composition (using BMI, TSF
      and MUAC parameters), serum biomarkers and offered dietary counseling. The data
      obtained at each visit (D15, D30, D60, D90, D120, D150, and D180) were analyzed,
      showing trajectories over time and central tendencies each time. RESULTS: at
      baseline, the mean age was 41.1 (+/- 13.4) years; they were predominantly male,
      with income lower than a local minimum wage and at least six years of schooling.
      Patients showed predominantly pulmonary tuberculosis. At baseline, all patients
      suffered from malnutrition. The overall energy malnutrition prevalence was of
      70.6%. Anemia at baseline was observed in both groups (63.2%), however, it was
      significantly more pronounced in the HIV+. At the end, energy malnutrition was
      reduced to 57.1% (42.9% of HIV- and 71.4% of the HIV+). Micronutrients
      malnutrition was evident in 71.4% of the HIV- patients and 85.7% of HIV+ patients
      at the end of tuberculosis therapy. Using BMI (<= 18.5 kg/m2cutoff) as an index
      of malnutrition, it was detected in 23.9% of the HIV- and 27.3% of the HIV+
      patients at baseline, with no evident improvement over time; using TSF (<= 11.4mm
      as cutoff) or MUAC (<= 28.5cm as cutoff), malnutrition was detected in 70.1% and
      85.3% of all patients, respectively. Nevertheless, combining all biomarkers, at
      the end of follow-up, all patients suffered from malnutrition. CONCLUSION:
      Although with a limited number of patients, the evidence does not support that
      dietary counseling is effective to recover from malnutrition in our population.

PMID- 26313260
TI  - The Impact of Goal Disturbance after Cancer on Cortisol Levels over Time and the
      Moderating Role of COMT.
AB  - Due to physical hindrance and time spent in hospital, a cancer diagnosis can lead
      to disturbance of personally important goals. Goal disturbance in cancer patients
      has been related to poorer psychological well-being. However, the relation with
      physiological measures is yet unknown. The purpose of the current study is to
      examine the impact of goal disturbance on cortisol as a measure of response to
      stress over time, and a possibly moderating role of a DNA genotype associated
      with HPA-axis functioning, Catechol-O-Methyl transferase (COMT). We examined the
      predictive value of goal disturbance on Cortisol Awakening Response (CAR) and
      Diurnal Cortisol Slope (DCS) over two periods: 1-7 and 7-18 months post
      diagnosis, and the moderating role of COMT during these periods. Hierarchical
      regression analyses showed that goal disturbance 7 months post-diagnosis
      significantly predicted a steeper CAR a year later. During that period, the slow
      COMT variant moderated the relation, in that patients reporting high goal
      disturbance and had the Met/Met variant, had a more flattened CAR. No other
      significant effects were found. As steeper CARs have been related to adverse
      health outcomes, and COMT genotype may modify this risk, these results indicate
      that goal disturbance and genotype may be important factors to consider in
      maintaining better psychological and physical health in the already vulnerable
      population of cancer patients. 

PMID- 26313261
TI  - 8-Chloroadenosine Sensitivity in Renal Cell Carcinoma Is Associated with AMPK
      Activation and mTOR Pathway Inhibition.
AB  - The adenosine analog 8-chloroadenosine has been shown to deplete ATP and inhibit
      tumor growth in hematological malignancies as well as in lung and breast cancer
      cell lines. We investigated effects of 8-chloroadenosine on clear cell (cc) renal
      cell carcinoma (RCC) cell lines. 8-chloroadenosine was effective against ccRCC
      cell viability in vitro, with IC50 ranging from 2 MUM in the most sensitive CAKI
      1 to 36 MUM in the most resistant RXF-393. Proteomic analysis by reverse-phase
      protein array revealed that 8-chloroadenosine treatment leads to inhibition of
      the mTOR pathway. In time-course experiments, 8-chloroadenosine treatment rapidly
      activated AMPK, measured by AMPK and ACC phosphorylation, and subsequently caused
      dephosphorylation of p70S6K and ribosomal protein RPS6 in the sensitive cell
      lines. However, in the resistant cell lines, AMPK activity and the mTOR pathway
      were unaffected by the treatment. We also noted that the resistant cell lines had
      elevated basal levels of phospho RPS6 and AKT. Inhibition of PI3K pathway
      enhanced the efficacy of 8-chloroadenosine across all cell lines. Our
      observations indicate that 8-chloroadenosine activity is associated with
      inhibition of the mTOR pathway, and that phospho RPS6 and PI3K pathway activation
      status may determine resistance. Among solid tumors, RCC is one of the few
      susceptible to mTOR inhibition. We thus infer that 8-chloroadenosine may be
      effective in RCC by activating AMPK and inhibiting the mTOR pathway. 

PMID- 26313262
TI  - Pseudotannins self-assembled into antioxidant complexes.
AB  - Natural tannins are attractive as building blocks for biomaterials due to their
      antioxidant properties and ability to form interpolymer complexes (IPCs) with
      other macromolecules. One of the major challenges to tannin usage in biomedical
      applications is their instability at physiological conditions and a lack of
      control over the purity and reactivity. Herein, we report the synthesis and
      characterization of tannin-like polymers with controlled architecture,
      reactivity, and size. These pseudotannins were synthesized by substituting linear
      dextran chains with gallic, resorcylic, and protocatechuic pendant groups to
      mimic the structure of natural hydrolysable tannins. We demonstrate that these
      novel materials can self-assemble to form reductive and colloidally stable
      nanoscale and microscale particles. Specifically, the synthesis, turbidity,
      particle size, antioxidant power, and cell uptake of IPCs derived from
      pseudotannins and poly(ethylene glycol) was evaluated. 

PMID- 26313263
TI  - Participatory Patterns in an International Air Quality Monitoring Initiative.
AB  - The issue of sustainability is at the top of the political and societal agenda,
      being considered of extreme importance and urgency. Human individual action
      impacts the environment both locally (e.g., local air/water quality, noise
      disturbance) and globally (e.g., climate change, resource use). Urban
      environments represent a crucial example, with an increasing realization that the
      most effective way of producing a change is involving the citizens themselves in
      monitoring campaigns (a citizen science bottom-up approach). This is possible by
      developing novel technologies and IT infrastructures enabling large citizen
      participation. Here, in the wider framework of one of the first such projects, we
      show results from an international competition where citizens were involved in
      mobile air pollution monitoring using low cost sensing devices, combined with a
      web-based game to monitor perceived levels of pollution. Measures of shift in
      perceptions over the course of the campaign are provided, together with insights
      into participatory patterns emerging from this study. Interesting effects related
      to inertia and to direct involvement in measurement activities rather than
      indirect information exposure are also highlighted, indicating that direct
      involvement can enhance learning and environmental awareness. In the future, this
      could result in better adoption of policies towards decreasing pollution. 

PMID- 26313264
TI  - Comparison of invasive and noninvasive blood pressure measurements in
      anaesthetized horses using the Surgivet V9203.
AB  - OBJECTIVES: To determine the bias and precision of noninvasive versus invasive
      blood pressure measurements obtained using the Surgivet V9203 in anaesthetized
      horses; to compare these with the current American College of Veterinary Internal
      Medicine Hypertension Consensus Panel (AHCP) and Veterinary Blood Pressure
      Society (VBPS) recommendations; and to investigate whether noninvasive blood
      pressure monitoring could be a clinically useful alternative to invasive blood
      pressure monitoring in anaesthetized horses. STUDY DESIGN: Prospective clinical
      study in a university teaching hospital. ANIMALS: Forty-three horses with an
      average weight of 485 +/- 90 kg and a mean age of 103.4 +/- 57.6 months. METHODS:
      Arterial blood pressure (BP) was measured noninvasively (NIBP) via a cuff placed
      over either the ventral coccygeal artery or the metacarpal artery, and invasively
      (IBP) via a catheter in either the facial artery or the metatarsal artery. A
      total of 143 paired readings were obtained. Comparison of measurements was
      carried out using the Bland-Altman method. Analysis was performed using all the
      data, and these data were subdivided according to the position of the horse and
      the magnitude of the pressure measurement. To determine the accuracy of the
      noninvasive measurements, the calculated precision and bias were compared with
      AHCP and VBPS guidelines. RESULTS: For all categories, NIBP measurements were
      generally lower than IBP measurements. For pooled data, the bias and precision
      for systolic arterial pressure (SAP) were 6.8 and 11.9 mmHg; for mean arterial
      pressure (MAP) the values were 1.9 and 10.0 mmHg; and for diastolic arterial
      pressure (DAP) they were 5.7 and 10.8 mmHg. The bias and precision for MAP and
      DAP measurements were within the recommended guidelines defined by the AHCP and
      VBPS. CONCLUSIONS AND CLINICAL RELEVANCE: These results suggests that systolic,
      mean and diastolic NIBP measured using the Surgivet V9203 are a clinically
      acceptable alternative to IBP measurements in anaesthetized horses undergoing
      routine elective surgeries.

PMID- 26313265
TI  - High throughput screening of cytokines, chemokines and matrix metalloproteinases
      in wound fluid induced by mammary surgery.
AB  - OBJECTIVE: To clarify the composition of wound fluid (WF) and investigate the
      impact of WF on breast cancer cell lines. METHODS: The proliferation and
      migration of WF-treated breast cancer cells MDA-MB-231 and MCF-7 were assessed
      with colony formation test, MTT cell proliferation test and scratch wound test.
      The quantitative profiles of WF were analyzed using Bio-Plex Pro kits. RESULTS:
      The proliferation and migration of WF-treated breast cancer cells were
      significantly higher than that of untreated cells. Fifteen cytokines, 29
      chemokines and 9 matrix metalloproteinases (MMPs) were assessed in WF. The
      concentrations of these factors were influenced by post-surgery days, neoadjuvant
      chemotherapy (NAC), TNM stage, pathological type and molecular subtype. The WF
      harvested from patients underwent NAC showed significant higher profiles of
      interleukin-1beta (IL-1beta), IL-4, IL-6, IL-17F, IL-21, IL-23, IL-25, IL-31,
      Interferon gamma (IFNgamma), CD40 ligand (CD40L), tumor necrosis factor alpha
      (TNFalpha), CXCL1, CXCL2, CXCL5, CCL3, CCL7 and CCL20. CONCLUSIONS: Surgery
      induced WF promotes the proliferation and migration of breast cancer cells. The
      composition of WF is influenced by various clinical features and provides
      potential therapeutic targets to control local recurrence and tumor progression.

PMID- 26313267
TI  - Computer-aided diagnosis: detection and localization of prostate cancer within
      the peripheral zone.
AB  - We propose a methodology for prostate cancer detection and localization within
      the peripheral zone based on combining multiple segmentation techniques. We
      extract four image features using Gaussian and median filters. Subsequently, we
      use each image feature separately to generate binary segmentations. Finally, we
      take the intersection of all four binary segmentations, incorporating a model of
      the peripheral zone, and perform erosion to remove small false-positive regions.
      The initial evaluation of this method is based on 275 MRI images from 37
      patients, and 86% of the slices were classified correctly with 87% and 86%
      sensitivity and specificity achieved, respectively. This paper makes two
      contributions: firstly, a novel computer-aided diagnosis approach, which is based
      on combining multiple segmentation techniques using only a small number of simple
      image features, and secondly, the development of the proposed method and its
      application in prostate cancer detection and localization using a single MRI
      modality with the results comparable with the state-of-the-art multimodality and
      advanced computer vision methods in the literature. Copyright (c) 2015 John Wiley
      & Sons, Ltd.

PMID- 26313266
TI  - CP-154,526 Modifies CREB Phosphorylation and Thioredoxin-1 Expression in the
      Dentate Gyrus following Morphine-Induced Conditioned Place Preference.
AB  - Corticotropin-releasing factor (CRF) acts as neuro-regulator of the behavioral
      and emotional integration of environmental and endogenous stimuli associated with
      drug dependence. Thioredoxin-1 (Trx-1) is a functional protein controlling the
      redox status of several proteins, which is involved in addictive processes. In
      the present study, we have evaluated the role of CRF1 receptor (CRF1R) in the
      rewarding properties of morphine by using the conditioned place preference (CPP)
      paradigm. We also investigate the effects of the CRF1R antagonist, CP-154,526, on
      the morphine CPP-induced activation of CRF neurons, CREB phosphorylation and Trx
      expression in paraventricular nucleus (PVN) and dentate gyrus (DG) of the mice
      brain. CP-154,526 abolished the acquisition of morphine CPP and the increase of
      CRF/pCREB positive neurons in PVN. Moreover, this CRF1R antagonist prevented
      morphine-induced CRF-immunoreactive fibers in DG, as well as the increase in
      pCREB expression in both the PVN and DG. In addition, morphine exposure induced
      an increase in Trx-1 expression in DG without any alterations in PVN. We also
      observed that the majority of pCREB positive neurons in DG co-expressed Trx-1,
      suggesting that Trx-1 could activate CREB in the DG, a brain region involved in
      memory consolidation. Altogether, these results support the idea that CRF1R
      antagonist blocked Trx-1 expression and pCREB/Trx-1 co-localization, indicating a
      critical role of CRF, through CRF1R, in molecular changes involved in morphine
      associated behaviors. 

PMID- 26313268
TI  - Effects of UGT1A1 genotype on the pharmacokinetics, pharmacodynamics, and
      toxicities of belinostat administered by 48-hour continuous infusion in patients
      with cancer.
AB  - The histone deacetylase inhibitor belinostat is eliminated through
      glucuronidation by UGT1A1. Polymorphisms that reduce UGT1A1 function could result
      in increased belinostat exposure and toxicities. We wanted to determine which
      single-nucleotide polymorphisms alter belinostat exposure and toxicity. In a
      phase 1 trial (belinostat over 48 hours in combination with cisplatin and
      etoposide), belinostat (400, 500, 600, or 800 mg/m(2) /24 h, 48-hour continuous
      infusion) was administered to patients with cancer in combination with cisplatin
      and etoposide (n = 25). Patients were genotyped for UGT1A1 variants associated
      with reduced function: UGT1A1*6, UGT1A1*28, and UGT1A1*60. End points were
      associations between UGT1A1 genotype and belinostat pharmacokinetics (PK),
      toxicities, and global protein lysine acetylation (AcK). Belinostat AUC was
      increased (P = .003), and t1/2 increased (P = .0009) in UGT1A1*28 and UGT1A1*60
      carriers who received more than 400 mg/m(2) /24 h. The incidence of grades 3-4
      thrombocytopenia (P = .0081) was associated with UGT1A1 polymorphisms. The US
      Food and Drug Administration-approved package insert recommends dose adjustment
      of belinostat for UGT1A1*28. However, our data suggest dose adjustment is also
      necessary for UGT1A1*60. UGT1A1 polymorphisms were associated with increased
      systemic belinostat exposure, increased AcK, and increased incidence of
      toxicities, particularly at doses > 400 mg/m(2) /24 h. 

PMID- 26313269
TI  - Building Research and Development Capacity for Neglected Tropical Diseases
      Impacting Leishmaniasis in the Middle East and North Africa: A Case Study.

PMID- 26313270
TI  - Nickel-Catalyzed Cross-Coupling of Anisoles with Alkyl Grignard Reagents via C-O
      Bond Cleavage.
AB  - Nickel-catalyzed cross-coupling of methoxyarenes with alkyl Grignard reagents,
      which involves the cleavage of the C(aryl)-OMe bond, has been developed. The use
      of 1,3-dicyclohexylimidazol-2-ylidene as a ligand allows the introduction of a
      variety of alkyl groups, including Me, Me3SiCH2, ArCH2, adamantyl, and
      cyclopropyl. The method can also be used for the alkylative elaboration of
      complex molecules bearing a C(aryl)-OMe bond. 

PMID- 26313271
TI  - Reproducibility of Circulating MicroRNAs in Stored Plasma Samples.
AB  - BACKGROUND: Most studies of microRNA (miRNA) and disease have examined tissue
      specific expression in limited numbers of samples. The presence of circulating
      miRNAs in plasma samples provides the opportunity to examine prospective
      associations between miRNA expression and disease in initially healthy
      individuals. However, little data exist on the reproducibility of miRNAs in
      stored plasma. METHODS: We used Real-Time PCR to measure 61 pre-selected microRNA
      candidates in stored plasma. Coefficients of variation (CVs) were used to assess
      inter-assay reliability (n = 15) and within-person stability over one year (n =
      80). Intraclass correlation coefficients (ICCs) and polychoric correlation
      coefficients were used to assess within-person stability and delayed processing
      reproducibility (whole blood stored at 4 degrees C for 0, 24 and 48 hours; n = 12
      samples). RESULTS: Of 61 selected miRNAs, 23 were detected in at least 50% of
      samples and had average CVs below 20% for inter-assay reproducibility and 31 for
      delayed processing reproducibility. Ten miRNAs were detected in at least 50% of
      samples, had average CVs below 20% and had ICCs above 0.4 for within-person
      stability over 1-2 years, six of which satisfied criteria for both interassay
      reproducibility and short-term within-person stability (miR-17-5p, -191-5p, -26a
      5p, -27b-3p, -320a, and -375) and two all three types of reproducibility (miR-27b
      3p and -26a-5p). However, many miRNAs with acceptable average CVs had high
      maximum CVs, most had low expression levels, and several had low ICCs with
      delayed processing. CONCLUSIONS: About a tenth of miRNAs plausibly related to
      chronic disease were reliably detected in stored samples of healthy adults.

PMID- 26313272
TI  - Factors associated with negative co-parenting experiences in families of a child
      with autism spectrum disorder.
AB  - PURPOSE: The purpose of this study was to identify key factors associated with
      negative co-parenting experiences in parents raising a child with autism spectrum
      disorder. METHODS: Questionnaires were sent to families with one or more children
      with a diagnosis of autism spectrum disorder. Parents of 142 children with autism
      spectrum disorder indicated that the diagnosis had a very negative impact on
      their co-parent relationship. A multivariate logistic regression model was run to
      analyze the association of these experiences with various demographic, family and
      community factors. RESULTS: Three factors were associated with negative co
      parenting relationships: (1) family stress due to the child's diagnosis, (2)
      effects of the diagnosis on parents' relationship with their other children and
      (3) distance travelled to the nearest medical facility. CONCLUSIONS: Findings
      highlight the need to further explore family dynamics, particularly the
      relationships between the co-parenting alliance, other family members and the
      extra-familial environment.

PMID- 26313273
TI  - [Carriage of Streptococcus pyogenes in primary school children: M-protein types,
      pyrogenic toxin genes, and investigation of the clonal relationships between the
      isolates].
AB  - M-protein and pyrogenic toxins are the most important virulence factors of
      Streptococcus pyogenes, and they play significant role in the pathophysiology of
      acute rheumatoid fever and scarlet fever, respectively. In this study, the
      pharyngeal carriage of S.pyogenes of the primary school children, clonal
      relationship of the strains, M-protein types, and the presence of pyrogenic toxin
      genes were aimed to be investigated. A total of 668 throat cultures obtained from
      children (age range: 6-16 years) in two primary schools in our region, were
      included in the study. The clonal relationships of the isolated group A
      streptococci (GAS) strains were investigated by DiversiLab assay (BioMerieux,
      France), and the clonal relatedness was confirmed by pulsed-field gel
      electrophoresis (PFGE) method. M-protein (emm) typing was performed by DNA
      sequencing as suggested by Centers for Disease Control and Prevention (CDC). The
      genes encoding pyrogenic toxins, speA and speC, were investigated by an in-house
      multiplex polymerase chain reaction (PCR) method. S.pyogenes was isolated from
      134 (20.05%) of the throat samples. The GAS carriage rate of the students aged
      >=10 was statistically higher than those 7-9 years age group (%22 vs %16.4,
      p<0.05). The M protein gene could be characterized only among 123 isolates by DNA
      sequencing, and 20 different emm types were detected. The most frequent emm type
      was emm1 (n=38, 30.9%) followed by emm12 (n=18, 14.6%), emm89 (n=10, 8.1%),
      emm118 (n=9, 7.3%), and emm4 (n=7, 5.7%). Pyrogenic toxin genes were found in 25
      (18.6%) of the isolates, including speA in 11 isolates (8.2%) and speC in 12
      isolates (8.9%) and both genes were detected in 2 isolates (1.5%). Sixty-two
      different Rep (Repetitive extragenic palindromic)-PCR profiles were detected in
      134 S.pyogenes isolates by DiversiLab method. Thirteen different clusters were
      formed by a total of clonally related 36 isolates revealing a strain clustering
      ratio of 26.9%. Clonal relationship of all isolates in the same cluster was
      confirmed by PFGE method. In this study, relatively high percentage of GAS
      carriage was observed among primary school children in our region. The coverage
      rate of the 30-valent vaccine was determined to be over 90% with respect to M
      protein types. Since the pyrogenic toxin-encoding genes were found in one fifth
      of the isolates from the studied subjects, we concluded that the carrier
      population may also have high risk for scarlet fever. We also concluded that, the
      clonal relationship ratio determined among the isolates may be a risk in school
      transmission of GAS.

PMID- 26313274
TI  - [Investigation of the protective effects of beta-D-glucan against invasive
      encapsulated Streptococcus pneumoniae sepsis in splenectomized rats].
AB  - In asplenic individuals depending on the weakness of the immune response, sepsis
      are known to be developed with a high mortality rate. The most common species
      which are responsible for sepsis are encapsulated bacteria such as Streptococcus
      pneumoniae, Haemophilus influenzae and Neisseria meningitidis. Sepsis caused by
      immune deficiencies linked to splenectomy leads to infections particularly in the
      lungs and liver and causes multiple organ failure. On the other hand, ?-D-glucan
      (BDG), a branched glucose polymer, shows immunomodulatory activity, by enhancing
      the resistance of the host against microbial agents, and promotes phagocytic and
      proliferative activities of reticuloendothelial system. The aim of this
      experimental study was to investigate the effects of BDG alone and in combination
      with ceftriaxone on sepsis caused by encapsulated invasive S.pneumoniae serotype
      19F. A total of 36 Sprague-Dawley rats were used in the study, and the animals (6
      in each group) were equally divided into six groups as control, splenectomy,
      sepsis, BDG, ceftriaxone and BDG+ceftriaxone groups. Treatment groups were
      intravenously infected with S.pneumoniae 19F strain, and after sacrification,
      microbiological [bacterial counts (cfu/mL)], biochemical (myeloperoxidase
      activity, DNA oxidation, specific IgM and IgG levels) and histopathological
      analysis were performed in the tissue samples. In the study, BDG, ceftriaxone and
      BDG+ceftriaxone groups had statistically significant decrease in the amount of
      bacteria in all tissues when compared to the sepsis group (p<0.05). We
      demonstrated that, BDG alone or combined treatment partially recovered the low
      serum IgM levels in splenectomized rats (p<0.001 ve p<0.02, respectively) and
      completely inhibited oxidative DNA damage in lung and liver after S.pneumoniae
      infection (p<0.00001). In addition, BDG alone or combined treatment fairly
      minimized the presence of bacteria in all tissues, when compared with sepsis
      group (p<0.00001). The data of our study suggests that, BDG, an immunomodulatory
      agent, alone and in combination with ceftriaxone can reverse the systemic
      inflammatory reaction in S.pneumoniae sepsis and thereby can reduce multiple
      organ failure.

PMID- 26313275
TI  - [Is there a relationship between rectal colonization and nosocomial infection of
      patients in intensive care unit?].
AB  - Nosocomial infections caused by multidrug-resistant (MDR) microorganisms are a
      major problem in intensive care units (ICUs) with high mortality and morbidity
      rates and the prior colonization is an important risk factor for these
      infections. The aim of this study was to investigate the prevalence of rectal
      colonization of MDR microorganisms and the association between the microorganisms
      that caused colonization and infection in the patients with nosocomial infections
      in ICUs. Rectal swabs were obtained on the day of 0, 3, 7, 14, 21 and weekly
      thereafter from 80 patients over 18 years of age hospitalized in ICU for more
      than 48 hours, and cultured for vancomycin-resistant enterococcus (VRE),
      methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta
      lactamase (ESBL)- producing gram-negative bacilli (GNB) and carbapenem-resistant
      enteric and nonenteric bacilli. Patients whose rectal swabs were not obtained on
      admission (on the day of 0), were excluded even they were hospitalized more than
      48 hours. Bile esculin agar containing 64 MUg/mL ceftazidime and 6 MUg/mL
      vancomycin, chromogenic MRSA agar and blood agar media, MacConkey agar containing
      1 mg/L ceftazidime and ceftriaxone, and 5 mL tryptic soy broth media containing
      10 ug imipenem and meropenem discs were used for identification. Identification
      of GNB was determined by conventional methods and ESBL production was determined
      by double-disc synergy test. Patients have been followed up for nosocomial
      infections. Bacterial identification and antibiotic susceptibility tests were
      performed with standard microbiological methods. In 37 (46%) of the 80 patients,
      at least one MDR microorganism was isolated in rectal swab cultures on the day of
      0. The most common microorganisms were ESBL-positive E.coli (19%), followed by
      ESBL-positive K.pneumoniae (13%), carbapenem-resistant P.aeruginosa (10%), ESBL
      positive K.oxytoca (3%), MRSA (1%), VRE (1%), carbapenem-resistant Acinetobacter
      sp. (1%) and carbapenem-resistant K.pneumoniae (1%), respectively. The number of
      microorganisms isolated from rectal swab cultures on the following days have
      increased, and on the 7th day, the rate of the patients with rectal colonization
      ascended to 72%. Out of 80 patients, 52 (65%) had nosocomial infections in the
      follow-up and the mean duration of infection development was 11.8+/-9.9 days in
      these patients. Patients with and without rectal colonization were compared in
      terms of subsequent nosocomial infection rates. While no statistically
      significant difference has been detected between two groups on the day of 0,
      patients with rectal colonization detected on the day of 3 and 7, had a
      significantly higher incidence of nosocomial infections (p=0.02, p=0.01). Among
      the patients with ESBL-positive GNB, carbapenem-resistant K.pneumoniae,
      carbapenem-resistant P.aeruginosa and VRE infections, the same microorganisms
      have been isolated in the rectal swab cultures taken before the development of
      infection. This result was statistically significant for each of these
      microorganisms (p=0.00-0.03). However, such a correlation was not observed for
      Acinetobacter infections. Since MRSA infections developed in only two patients,
      no istatistical analysis has been done for this microorganism. In conclusion, our
      data suggest that MDR microorganisms that cause nosocomial infections, initially
      colonize the gastrointestinal tract, and early detection of colonized patients in
      ICUs may help an effective infection control by preventing the spread of these
      resistant microorganisms.

PMID- 26313276
TI  - [Can curcumin prevent the formation of Pseudomonas aeruginosa biofi lm on the
      surface of tympanostomy tubes?].
AB  - Formation of bacterial biofilm on the surface of tympanostomy tubes are held
      responsible in the pathogenesis of post-tympanostomy tube otorrhea. To prevent
      the formation of biofilm, various methods were employed and varying degrees of
      success have been achieved. In some recent studies curcumin, which is the fenolic
      form of Curcuma longa (turmeric), has been pointed out to have inhibitory effects
      on virulence factors of Pseudomonas aeruginosa. The aim of this study was to
      investigate whether the administration of curcumin is able to prevent the
      formation of P.aeruginosa biofilm on the surface of silicone tympanostomy tubes
      in vitro conditions. For this purpose, qualitative and quantitative analysis of
      P.aeruginosa biofilm created on the surface of the tympanostomy tubes were
      performed following a period of 48 hours incubation in microplate wells that
      contained decreasing concentrations of curcumin. For qualitative analysis,
      specimens were evaluated with an environmental scanning electron microscope for
      the existence of biofilm. For the quantitative analysis, bacteria attached to the
      tube surface was detached using a combination of vortexing and sonication.
      Following serial dilutions, the obtained solution was then inoculated on the
      sheep blood agar plates using calibrated loop, incubated for 24 hours and the
      colony forming unit (CFU) per mL were recorded. Environmental scanning electron
      microscope analysis revealed that 100 ug/mL of curcumin could prevent formation
      of the biofilm. Lower concentrations of curcumin could not prevent the biofilm
      formation. Qualitative analysis also revealed that when the concentrations of
      curcumin in the wells were decreased, the number of CFU/mL was increased
      significantly. Mean number of CFU in 100 ug/mL and 12.5 ug/mL groups were 35+/
      7.07 and 650+/-494, respectively. Curcumin could prevent formation of
      P.aeruginosa biofilm on the surface of tympanostomy tubes in vitro with
      concentrations lower than the MIC value. The results of the present study show
      that local administration of curcumin may prevent suppurative otitis media
      following tympanostomy tube insertion, keep the patency of the tube and decrease
      the rate of treatment failure. In vivo studies are needed to support the in vitro
      anti-biofilm action of curcumin on tympanostomy tubes.

PMID- 26313277
TI  - [Changes in antibiotic resistance of Pseudomonas aeruginosa isolates over the
      past 11 years in Turkey: a meta-analysis].
AB  - The increased antibiotic resistance and diversity of resistance mechanisms in
      clinical isolates of Pseudomonas aeruginosa lead to serious problems in
      treatment. Bacterial resistance against antibiotics can be influenced by patient
      characteristics, antibiotic usage policy depending on the country, region,
      hospital, clinics and even may vary during treatment. In this meta-analysis
      study, we aimed to evaluate the trends in P.aeruginosa antibiotic resistance over
      the past 11 years. The study was planned and conducted in accordance with the
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and
      the literature search method, criteria for inclusion and exclusion, evaluation of
      publications, data collection, and statistical analysis were performed. To
      identify relevant publications, two national databases (ULAKBIM and TURK MEDLINE)
      and one international database (PubMed) were searched. Published manuscripts were
      evaluated for exclusion criteria, after the study data were collected, and
      statistical analyses were performed. The data obtained from the literature were
      assessed under a common unit. The calculations made in the 95% confidence
      interval value of p<=0.05 was considered statistically significant. As a result
      of exclusion criteria, meta-analysis was performed for 48 studies published
      between 2003 and 2013. For the evaluation of the changes in antibiotic resistance
      of P.aeruginosa isolates over time, studies were divided into three groups
      according to the year of publication. The number of publications was relatively
      consistent over the course of the study period with 17 studies published in 2003
      2006; 14 in 2007-2009, and 17 in 2010-2013. There were significant changes in
      antibiotic resistance results within years however, none of these differences
      were statistically significant (p>0.05). Carbapenem resistance, especially
      imipenem resistance, increased between 2007 and 2009, however, the changes were
      not statistically significant for either imipenem or meropenem (p=0.254, p=0.499,
      respectively). Through the 11-year period, the resistance rates for imipenem and
      meropenem were 29.4% and 32.1%, respectively. In the last 4 years of the study
      period, notable decrease were reported in antibiotic groups except for cefepime
      from cephalosporins and monobactam; the resistance rates for cephalosporins
      remained unchanged during this time period. The reported resistance rates for
      cefepime and ceftazidime were 41.4% and 43.9%, respectively. Similar decreases in
      resistance to aminoglycoside antibiotics, including amikacin, gentamicin,
      netilmicin, and tobramycin, were also seen, however, these changes were not
      statistically significant (p>0.05). The current data suggested that antibiotic
      resistance in P.aeruginosa has a tendency to decrease in our country. Though
      being at the bottom of the ladder, it can be expressed that rational and
      restricted use of antibiotics policy, contributed to the strength of the
      decrease; however for the decline of resistance to a reasonable level, new and
      sustainable policy is necessary to be implemented.

PMID- 26313278
TI  - [Using Galleria mellonella as an in vivo model to study the virulence of some
      bacterial and fungal agents].
AB  - Non-vertebrate hosts, such as Galleria mellonella, namely wax moth, have been
      used to study microbial virulence and host defense. This organism has advantages
      as it is economical, ethically expedient and easy to handle. Here we describe an
      experimental in vivo study using the larvae of Galleria mellonella infected with
      some bacterial and fungal pathogens. In this study, extended-spectrum beta
      lactamase (ESBL) producing and non-producing Escherichia coli, Klebsiella
      pneumoniae and Pseudomonas aeruginosa, colistin resistant and susceptible
      Acinetobacter baumanii clinical strains; Candida albicans (ATCC 10231),
      Scedosporium aurantiacum (CBS 136047) and Pseudallescheria boydii (CBS 117410)
      reference strains, and Aspergillus terreus and Fusarium oxysporum clinical
      strains were used as pathogens. The larvae of G.mellonella were challenged with
      these bacterial and fungal strains, and the mortality rates were calculated using
      Kaplan-Meier plots. Mortality rates at 16th hour were found as 83% for the larvae
      infected with both ESBL positive and negative E.coli, ESBL negative K.pneumoniae
      and ESBL positive P.aeruginosa; 91% for ESBL positive K.pneumoniae; 75% for ESBL
      negative P.aeruginosa; 66% for both colistin resistant and susceptible A.baumanii
      strains. All larvae infected with bacteria died within the first 24 hour. Larvae
      infected with bacteria showed significantly higher mortality rates than those
      infected with fungi. Mortality rates at 16th hour were found as 0% for C.albicans
      and F.oxysporum, 16% for S.aurantiacum, 8% for P.boydii and A.terreus; at 24th
      hour that was 25% for C.albicans and P.boydii, 33% for S.aurantiacum, A.terreus
      and F.oxysporum; at 48th hour that was 33% for C.albicans, 50% for P.boydii and
      F.oxysporum, 58% for A.terreus, and 66% for S.aurantiacum; in 72 hours that was
      58% for C.albicans and F.oxysporum, 66% for P.boydii, 75% for A.terreus and
      S.aurantiacum, in 96 hours that was 83% for C.albicans, P.boydii and F.oxysporum,
      91% for A.terreus and S.aurantiacum. As a result of this study, potential
      evidences provided that bacteria were more virulent than fungi for G.mellonella
      larvae model, each fungal species showed different virulence patterns, and
      bacterial virulence was correlated neither with species nor antibiotic
      susceptibility. 

PMID- 26313279
TI  - [Characterization of basal core promoter/precore gene mutations in chronically
      infected patients with hepatitis B virus genotype D in Mersin Province, Turkey].
AB  - The basal core promoter (BCP) and precore (PC) gene regions of hepatitis B virus
      (HBV) genome are important for the viral replication and synthesis of "e"
      antigen. Genetic variability has been described in PCP and PC gene regions,
      commonly in HBeAg negative patients. The aim of this study was to determine the
      frequency of the predominant mutation patterns of BCP/PC gene regions and their
      correlations with HBeAg status, HBV-DNA levels, and liver biochemical profiles in
      chronic hepatitis B (CHB) patients infected with genotype D, in Mersin province
      which is located at Mediteranean part of Turkey. A total of 54 CHB patients (33
      male, 21 female; mean age: 40.05+/-12.91 years) infected with HBV genotype D were
      enrolled in the study. Serum HBV-DNA levels, serological markers (HBsAg, anti
      HBs, HBeAg, anti-HBe, anti-HBc) and biochemical profiles (ALT and AST) were
      analyzed in all patients. BCP and PC gene regions were determined by polymerase
      chain reaction (PCR) and mutations of these regions were determined by direct
      sequencing of PCR products then aligned with known wild-type HBV sequences. BCP
      [nucleotide (nt.) 1753-1762/1764] and/or PC (nt. 1896) mutations were detected in
      87.75% (43/49) of the patients. Mutation rates were detected as 97.1% (33/34) and
      66.7% (10/15) in the HBeAg negative and in HBeAg positive patient groups,
      respectively (p=0.008). PC nt. G1896A mutation was more common in HBeAg negative
      samples than in HBeAg positive samples (73.5% vs. 20%, p=0.001), however there
      was no significant differences in the occurrence of BCP mutations between the two
      groups (p=0.331). No correlation was found between the presence of BCP and/or PC
      mutations and serum HBV-DNA or ALT-AST levels. Our study reveals that significant
      number of chronically infected patients with genotype D HBV have BCP and PC
      variants. G1896A stop codon mutation in precore region seems to have a
      significant role in the loss of HBeAg in our patients. The results of our study
      provided important data about the frequency and the genetic heterogeneity of
      different kinds of mutations occurring at BCP and PC gene regions.

PMID- 26313280
TI  - [Investigation of ganciclovir resistance in CMV UL54 and UL97 gene regions in
      immunocompromised patients receiving gancyclovir treatment].
AB  - Cytomegalovirus (CMV) is a main cause of severe morbidity and mortality in
      immunocompromised patients. Ganciclovir (GCV) is used for both prophylaxis and
      treatment of CMV disease with successful results, however GCV resistance has been
      increasingly reported. The aim of this study was to investigate the GCV
      resistance in patients whose viral loads did not decline (>=1000 copies/mL)
      despite of receiving GCV treatment, by using sequence analysis method. A total of
      30 patients, 25 of them were bone marrow transplant (BMT) and five who were
      followed in hematology clinics (non-Hodgkin lymphoma, lung cancer, diffuse large
      B cell lymphoma, combined immune deficiency, chronic lymphocytic leukemia) were
      included in the study. CMV-DNA levels were monitored by real-time polymerase
      chain reaction (QIAsymphony, Artus(r) CMV QS-RGQ kit, Qiagen, Germany), and DNA
      sequence analysis (ABI 310 Genetic Analyzer, Applied Biosystems, USA) was
      performed to detect the mutations leading to CMV antiviral drug resistance in
      following gene regions: 420-664 codons in UL97 gene region and 261 to 588 and 740
      to 987 codons in UL54 gene region. Of 30 patients included, M460V mutation in CMV
      UL97 gene region was detected in one (3.3%) (1st case) and L802M mutation in UL54
      gene region, in addition to P887S and S897L variant sequences in another patient
      (3.3%) (2nd case). The first patient was a 20-year-old male with acute myeloid
      leukemia who underwent BMT. The blood sample for the investigation of antiviral
      drug resistance was taken on the 117th day of transplantation (with simultaneous
      viral load 4470 copies/mL) and the patient has been using GCV for 70 days when
      the sample was taken. Valganciclovir (VGCV) and foscarnet (FOS) were used for the
      therapy of the first patient and monitored. The second patient was a 19-year-old
      male with acute lymphoblastic leukemia who underwent BMT. The blood sample for
      the investigation of antiviral drug resistance was taken on the 109th day of
      transplantation (with simultaneous viral load 4830 copies/mL) and the patient
      received GCV for 26 days and VGCV for 40 days when the sample was taken. FOS and
      cidofovir were used for the therapy of the second patient but the patient was
      lost due to the underlying diseases. In conclusion, mutations responsible for GCV
      resistance was detected in 6.6% (2/30) of immunocompromised patients receiving
      GCV, indicating that the determination of CMV antiviral drug resistance may help
      clinicians for planning the antiviral therapy. 

PMID- 26313281
TI  - [Serological investigation of phlebovirus exposure in blood donors from the
      Mediterranean Province of Mersin, Turkey].
AB  - Phleboviruses are enveloped segmented RNA viruses, capable of inducing febrile
      disease and/or meningoencephalitis in exposed individuals, according to the
      infecting strain, following transmission via arthropods. Prototype medically
      important phlebovirus strains responsible for sandfly fever are sandfly fever
      Sicilian virus (SFSV) and sandfly fever Naples virus (SFNV), where the SFSV
      variant sandfly fever Cyprus virus (SFCV) is also detected in individuals with
      febrile disease. Toscana virus (TOSV) is unique among phleboviruses as the cause
      of infections involving central nervous system. In this seroepidemiological
      study, human exposure to selected medically-important phleboviruses was
      investigated in healthy adult residents of the Mersin province, Mediterranean
      Anatolia, Turkey, where the current data on phlebovirus epidemiology is scarce. A
      total of 1784 healthy individuals (mean age: 34.7+/-9.6 years; 97.3% were male),
      accepted as blood donors at the Mersin University Center for Health Research and
      Application Blood Bank were included in the study after informed consent during a
      seventeen month period between July 2011 to November 2012. All participants were
      requested to fill out a questionnaire to reveal risk factors for vector exposure.
      SFSV, SFNV, SFCV and TOSV IgG antibodies in serum were investigated via a
      commercial indirect immunofluorescence test (IIFT) (Sandfly Fever Virus IgG
      Mosaic I; Euroimmun, Germany). Sera interpreted as positive or strong positive
      for TOSV or SFNV+TOSV in IIFT were evaluated via TOSV virus neutralization test
      (VNT) for specificity confirmation. IIFT seroreactivity for at least one of the
      tested phleboviruses was present in 66.8% (1192/1784) of the samples. The most
      frequently-detected phlebovirus strain was SFSV (51.6%; 920/1784), followed by
      SFNV (46.4%; 827/1784), TOSV (43.7%; 779/1784) and SFCV (47.3%; 843/1784). Among
      the reactive sera, 6.6% (79/1192) were positive for a single virus serotype,
      whereas in 39.8% (475/1192) antibodies reacting with all tested virus serotypes
      were revealed. A total of 187 sera was included in the TOSV VNT and neutralizing
      antibodies were detected in 13.9%. According to the IIFT reactivity, residing in
      rural areas was observed as a statistically significant risk factor for exposure
      in all phleboviruses tested (p values for SFSV, SFNV, TOSV and SFCV were 0.002,
      0.001, <0.001 and 0.003, respectively). TOSV exposure is more frequently detected
      via IIFT in individuals having pets or domestic farm animals around the living
      quarters (p=0.005). As a result, frequent exposure to SFSV/SFCV or antigenically
      similar phlebovirus strains and viruses of the SFNV species were determined in
      healthy blood donors in Mersin province, located in the Mediterranean region of
      Turkey. Furthermore, TOSV neutralizing antibodies were detected in selected
      samples with IIFT reactivity, confirming previous reports suggesting TOSV
      activity in the region. TOSV and other phleboviruses must be included in the
      diagnostic work-up in cases with febrile diseases and viral central nervous
      system infections during the sandfly-active months.

PMID- 26313282
TI  - [Molecular diagnosis and phylogenetic analysis of the first MERS case in Turkey].
AB  - Coronaviruses (CoV) are enveloped, spherical, single-stranded positive-sense RNA
      viruses causing mainly respiratory and intestinal infections in animals and
      humans. Until recently five types of human coronaviruses (HCoV-OC43, HCoV-HKU1,
      HCoV-NL63, HCoV-229E, SARS-CoV) have been known, however a novel CoV has been
      identified in 2012 in Saudi Arabia. This virus, namely MERS-CoV (Middle East
      Respiratory Syndrome Coronavirus), was classified within Coronaviridae family,
      Coronavirinae sub-family, Betacoronavirus genus, clade C. It causes acute
      respiratory infections in humans and transmits via respiratory route and close
      contact between humans. The aim of this study was to present the first MERS case
      from Turkey identified by molecular methods and the results of viral sequence
      analysis. A 42-year-old male Turkish citizen who worked as an employee in Jeddah,
      Kingdom of Saudi Arabia, admitted to hospital with the complaints of fever and
      malaise on 25-26 September 2014. Since his symptoms went on and got worse, he
      returned to Turkey, and hospitalized in a hospital's intensive care unit in Hatay
      on 6th of October with the symptoms of fever, malaise, sweating, cough and
      respiratory distress. He transferred to a university hospital on 8th of October
      and died on 11th October. The tracheal aspirate sample obtained before he died
      was sent to Virology Unit of Reference Laboratories of the Turkish Public Health
      Institution. Detection of viral RNA was performed by using a commercial real-time
      PCR kit (hCoV-EMC Real-Time RT-PCR, Fast Track Diagnostics, Luxembourg) targeting
      the MERS-CoV E protein (upE), ORF1a and ORF1b gene regions. The reference method
      Superscript III One Step RT-PCR (Invitrogen, USA) recommended by World Health
      Organization (WHO) was also applied for confirmation. Both of the methods yielded
      positive results for MERS-CoV RNA. For the amplification of nucleocapsid (N) and
      RNA-dependent RNA polymerase (RdRp) genes, hemi-nested PCR (Invitrogen, ABD) was
      conducted, followed by sequence analysis of 204 nucleotide part of N gene.
      Phylogenetic tree of N gene was obtained with the use of MEGA6 software. N gene
      was chosen as it comprised a two aminoacid deletion in the corresponding
      published sequence from the patient treated in London, United Kingdom. There was
      no nucleotide or aminoacid change in our isolate, namely ANK/1079/2014 when
      compared with human Betacoronavirus 2c EMC/2012 reference strain found in Genbank
      database. The target gene regions selected in our study (UpE, ORF1a, ORF1b, N and
      RdRp) which were also recommended by WHO, shown to have high specificity and
      sensitivity for the diagnosis and confirmation of MERS-CoV, and also recommended
      by WHO. The previous studies indicated that, the viral genomes detected in the
      earliest cases of humans (clade A) are genetically distinct from the others
      (clade B) which were isolated from dromedary camels and humans. In our study,
      according to phylogenetic analysis of partial N gene segment, isolate
      ANK/1079/2014 has taken place within clade A. In conclusion, MERS-CoV appears to
      have limited circulation in Arabian Peninsula and Middle-Eastern countries, it
      should be considered in mind that travel-related cases may export the virus
      outside these regions leading autochtonous infections in the other parts of the
      world. 

PMID- 26313283
TI  - [Investigation of the changes in Candida epidemiology].
AB  - The incidence of fungal infections has increased in recent years. Antifungal
      resistance is a major problem with increasing frequency due to the widespread use
      of antifungal agents in infections. Identification of the Candida species and
      susceptibility patterns with the appropriate tests for resistance and selection
      of the empirical agents used for treatment are important. The aim of the study
      was to evaluate the changes of the epidemiology of Candida species and minimum
      inhibitory concentrations (MIC) of the antifungal agents, isolated in Mycology
      Laboratory of Ondokuz Mayis University Faculty of Medicine, between 1 January
      2009 to 1 July 2012. The study was performed retrospectively based on records in
      the mycology unit and checked comparatively with the automation system in the
      hospital. The recurrent reproductions of the same patient were excluded. For the
      identification of Candida species API(r)ID 32C (bioMerieux, France) system was
      used. Information on the isolated material, patient's age, gender and the
      inpatients' clinics were recorded. The susceptibility of Candida species isolated
      from blood cultures were studied with Etest (bioMerieux, France) method. A total
      of 1238 isolates were included in the study. The most common species isolated
      from clinical samples was C.albicans with a rate of 51.1% (n= 632), followed by
      C.tropicalis with a rate of 15.8% (n= 195). Among the pediatric intensive care
      unit (ICU) patients C.parapsilosis 42% (n= 17) was the most common isolate and
      the second most common isolate was C.albicans 32% (n= 13). However, in the adult
      ICU the most common isolate was C.albicans 34% (n= 13) and the second was
      C.parapsilosis 31% (n= 12). When the distribution of Candida species were
      analyzed from the records of last four years, the frequency rate of C.albicans
      and non-albicans species was found as 51.1% (n= 632) and %48.9 (n= 606),
      respectively. Based on these data, a comparison was made between the years and no
      difference between the two groups in terms of the distribution of fungi within
      the specified time (x2: 3.2, df: 1, p: 0.073) was determined. Of the Candida
      species isolated from blood cultures, seven isolates (2.2%) were resistant to
      fluconazole in the study period. The differences of MIC levels in fluconazole
      were detected between the years 2010-2012 and 2011-2012. The geometric mean of
      the MICs in 2012 increased significantly compared to 2010 and 2011 (p< 0.01).
      There was no resistance to amphotericin B except for intrinsically resistant
      Candida lusitaniae. There were no significant differences among amphotericin MIC
      values between years (p> 0.05). According to the sensitivity results, fluconazole
      is still seen as an option that can be used for the first choice. Although it
      remains as the first antifungal choice, antifungal susceptibility testing of the
      identified fungi will help the clinician for the plan and continuation of the
      treatment. 

PMID- 26313284
TI  - [Investigation of the presence of Encephalitozoon intestinalis and Enterocytozoon
      bieneusi in bone marrow transplant patients by IFA-MAbs method].
AB  - Microsporidian pathogens are obligatory intracellular eukaryotic parasites which
      can be found worldwide. They have been represented in 144 genera and more than
      1200 species that may cause infections in both vertebrate and invertebrate hosts.
      Enterocytozoon bieneusi and Encephalitozoon intestinalis are the most common
      species among 14 species of microsporidia identified as human pathogens and they
      cause infections in the gastrointestinal tract. These species may also cause
      chronic diarrhea particularly in immunocompromised patients, as well as
      disseminated infections with severe clinical conditions which can be life
      threatening. Since the spores of microsporidia are quite small-sized structures,
      they frequently may be overlooked in routine stool examinations. Therefore,
      molecular methods and transmission electron microscopy, if possible, are used as
      the gold standard methods in laboratory diagnosis. In laboratories in which those
      methods could not be applied, immunofluorescence assay using monoclonal
      antibodies (IFA-MAbs) may be advantageous compared to conventional methods. The
      aim of this study was to investigate the presence of E.intestinalis and
      E.bieneusi in bone marrow transplant (BMT) patients by using IFA-MAbs method. A
      total of 200 BMT patients (134 male, 66 female; mean age: 43.2+/-15.01 years), of
      them 147 with diarrhea and 80 healthy subjects (43 male, 37 female; mean age:
      31.9+/-11.76 years) as control group were included in the study. All of the stool
      samples were examined by a commercial IFA-MAbs (Bordier Affinity Products,
      Switzerland) method as well as conventional (native-lugol and modified acid-fast
      staining) methods. Of the patients 25.5% (51/200) were positive for
      E.intestinalis, 4% (8/200) for E.bieneusi and 9.5% (19/200) for both of them,
      giving a total positivity rate of 39% (78/200). Those rates were 5% (4/80), 2.5%
      (2/80), 3.8% (3/80) and 11.3% (9/80), respectively for control group. The
      difference between the patient and control groups in terms of positivity was
      found statistically significant (39% vs 11.3%, p<0.05). Among 78 positive BMT
      patients, 67 (85.9%) were suffering from diarrhea. The correlation between the
      presence of diarrhea and the presence of microsporidia was statistically
      significant (p<0.05). It was concluded that, BMT patients particularly those with
      gastrointestinal complaints, have to be evaluated for microsporidian pathogens
      regularly to improve quality of life and to decrease the problems during the
      treatment period.

PMID- 26313285
TI  - [Seropositivity of Borrelia burgdorferi in risky groups in Van region, Turkey].
AB  - Lyme borreliosis, which is more prevalent in the northern hemisphere, is the most
      common tick-borne contagious disease among people living in the North America and
      Europe. The causative agent of Lyme borreliosis, Borrelia burgdorferi, is
      transmitted by the bites of ticks of the genus Ixodes. In Turkey, the
      seroprevalence of Lyme disease is increased in regions where ticks and tick-bite
      cases are prevalent. The present study aimed to determine the seroprevalence of
      Lyme borreliosis in people at risk, living in the rural areas of Van province,
      which is located in the eastern region of Turkey. No previous study on this topic
      has been performed in our province. The study included a total of 446 subjects
      (mean age: 39.6+/-15.5 years), of them 139 were male and 307 were female, living
      in the rural areas of Van province between January 2012 and July 2012. The serum
      samples collected from participants after informed consent were screened for the
      presence of B.burgdorferi IgG antibodies by ELISA method. Western blot (WB)
      method was used for the confirmation of positive or borderline positive samples,
      and also for the investigation of IgM antibodies. During the study, the
      individuals from whom samples were taken, were questioned whether they have ever
      been exposed to tick or insect bite. B.burgdorferi IgG positivity was detected in
      17 (3.8%) of the cases, whereas it was within the limit values in 14 cases. A
      total of 31 samples which yielded positive and borderline positive results were
      retested by WB and 4 (12.9%) were detected as positive while 10 (32.3%) of the
      samples were indeterminate. B.burgdorferi IgM antibody positivity was not
      detected in any of the samples. Considering the WB as reference method, the rate
      of B.burgdorferi IgG seropositivity was estimated as 0.9% (4/446). Three of these
      four cases were defined as tick or insect bites. The seroprevalence rate of
      B.burgdorferi detected in the present study was low as compared to the results of
      the other studies reported from Turkey. The reason of this result might be from
      the geographical characteristics and the differences of tick fauna in our region.
      As a result, it was concluded that our province is not endemic for Lyme
      borreliosis, however for the reduction of tick exposure, emphasis must be placed
      on preventive health services for the individuals at risk.

PMID- 26313286
TI  - [Invasive pneumococcal disease in two non-vaccinated pediatric cases: pleural
      empyema and bacteremia].
AB  - Streptococcus pneumoniae, a gram-positive diplococcus, is the causative agent of
      invasive pneumococcal diseases (IPDs) characterized by severe infections such as
      bacteraemia, sepsis and meningitis. S.pneumoniae and IPDs are situated in the
      focus of the vaccine studies because of being encompassed of a significant burden
      of disease in the world, severe mortality and morbidities, and location in
      vaccine-preventable diseases group. Although S.pneumoniae has more than 90
      defined serotypes, certain serotypes are often identified as the cause of IPDs.
      Individuals with comorbid and chronic diseases, primary or secondary immune
      deficiencies, and <2 years or >65 years of age are at increased risk for IPDs.
      Currently, a 23-valent polysaccharide vaccine and also 7, 10 and 13 valent
      pneumococcal conjugated vaccines (PCV) have been produced for pneumococci. Phase
      studies of protein based vaccines, which will provide protection independent of
      serotypes, and 15-valent pneumococcal conjugated vaccine are still ongoing. In
      Turkey, in November 2008 PCV7 and in April 2011 PCV13 have been implemented in
      the national immunization program. First case of the pneumococcal unvaccinated
      cases presented in this report was a 6-year-old girl patient with pneumonia and
      pleural empyema due to S.pneumoniae serotype 1, without any underlying risk
      factors. The other case is a 52-days-old male patient, who had a history of
      pneumococcal septicemia in the newborn period and was followed for bacteremia
      associated S.pneumoniae serotype 12B and diagnosed as complement deficiency on
      follow-up. S.pneumoniae serotype 1 is within serotypes covered by 10 and 13
      valent pneumococcal conjugate vaccines and pneumococcal polysaccharide vaccine
      that are in use today, and is a highly invasive strain often isolated in
      pneumococcal lobar pneumonia and empyema. S.pneumoniae serotype 12B is a non
      vaccine serotype not included in any of conjugate and polysaccharide vaccines,
      and usually obtained in respiratory infections and nasopharyngeal carriage
      studies. The first case of this report was presented because of an IPD with a
      serotype included in PCV13 implemented in the routine childhood vaccination
      schedule and to give an idea about pneumococcal strains circulating in the
      community. The second case was discussed to draw attention for the evaluation of
      immune deficiencies and other risk factors in recurrent infections with
      encapsulated bacteria such as pneumococci. Pneumococcal conjugate vaccines
      contribute the public immunity with the reduction of vaccine-type pneumococcal
      nasopharyngeal carriage, IPD incidence, and IPD associated morbidity and
      mortality especially in young children, at the same time cause a decrease in the
      prevalence of antibiotic-resistant infections. Application of the pneumococcal
      conjugate vaccines covering the whole society is important, according to all
      these important results.

PMID- 26313287
TI  - [A case of rib tuberculosis and chest wall abscess with multi-drug
      hypersensitivity reactions].
AB  - Extrapulmonary tuberculosis is the reactivation of the remaining latent organism
      which spreads during primary infection by the lymphohematogenous way. It should
      be considered in the differential diagnosis especially in endemic countries for
      tuberculosis. Tuberculosis (TB) treatment is based on the principle of the
      combined use of several drugs. As a result of the combination therapy there can
      be life threatening side effects which can lead to improper use of medications
      and may also cause drug resistance. In this report, we present an 85-year-old
      male patient desensitized due to the development of allergy against multi-drugs
      with rib tuberculosis and chest wall abscess to whom, culture, drug
      susceptibility and genotypical tests were applied. In November 2012, the patient
      applied to a medical center with complaints of swelling and pain under the right
      rib, underwent rib resection and eventually diagnosed as rib TB by
      histopathological examination. However, the anti-TB treatment was discontinued
      due to the hypersensitivity reactions in the skin and in addition to the hepatic
      and renal dysfunction side effects. The patient had widespread redness, rash and
      pruritus on the body and the laboratory findings were as follows; ALT: 114 U/L,
      AST: 152 U/L, ALP: 93 U/L, GGT: 26U/L, blood urea nitrogen (BUN): 26 mg/dL and
      creatinine: 1.7 mg/dL. After the disapperance of the complaints within 3 days of
      drug discontinuation, isoniazid treatment was initiated. However, the new
      treatment was also discontinued when the reactions reoccurred. Afterwards, the
      patient developed hypersensitivity reactions against the combination of
      streptomycin and ethambutol. The patient refused any further treatment and was
      discharged from the hospital. The patient was untreated for the last 5 months and
      admitted to our clinic with a fistulized swelling and abscess in the right chest
      wall. Bacteria was not detected in the acid-fast staining of the abscess
      material, however Mycobacterium tuberculosis was isolated from culture by MGIT
      (Mycobacteria Growth Incubator Tube; BBL MGIT, BD, USA) system. The spoligotyping
      revealed that the genotype was Haarlem 1. Major drug susceptibility testing
      against rifampin, streptomycin, ethambutol, isoniazid, and pyrazinamide yielded
      sensitivity to those drugs. Minor drug susceptibility testing against
      paraaminosalicylic acid, ethionamide, kanamycin, capreomycin and ofloxacin was
      found to be sensitive. A regimen of isoniazid 300 mg/day, ethambutol 1000 mg/day
      and moxifloxacin 400 mg/day was initiated. Rapid oral desensitization against
      isoniazid and ethambutol were repeated on two consecutive days. The patient
      continued antituberculosis therapy for 12 months without adverse reactions. The
      chest wall fistula was closed. Abscess was drained surgically. Clinical and
      radiological improvements were achieved. The patient remains clinically disease
      free and continues his regular follow ups. This case is presented to emphasize
      about the importance of culture and susceptibility testing in extrapulmonary
      tuberculosis cases and desensitization in drug hypersensitivity reactions. 

PMID- 26313288
TI  - [A case diagnosed with chronic granulomatous disease after disseminated infection
      following BCG vaccination].
AB  - BCG (Bacillus Calmette-Guerin) vaccine is a widely used vaccine with the
      recommendation of World Health Organization to protect children against miliary
      tuberculosis (TB) and TB meningitis. Severe side effects related to this vaccine
      mostly manifest in the presence of underlying immunosuppressive disease. In this
      report, an infant case with unknown chronic granulomatous disease (CGD) who
      developed disseminated BCG infection after administration of BCG vaccine, was
      presented. High fever, left axillary lymphadenopathy and hepatosplenomegaly have
      developed in a 3-month 28-day female infant, without a known health problem,
      following BCG vaccination. The acid-fast bacilli (ARB) was isolated from the
      material of excised lymph node cultivated in Lowenstein-Jensen medium, and the
      isolate was identified as Mycobacterium bovis. Mycobacterium tuberculosis complex
      DNA was detected in the axillary lymph node sample by polymerase chain reaction.
      Anti-tuberculous treatment included 20 mg/kg of rifampicin+10 mg/kg of
      isoniazid+15 mg/kg of ethambutol+30 mg/kg of streptomycin was started. The
      patient was then further evaluated for immunodeficiency and on the basis of the
      results of dihydroamine and LAD (lymphocyte adhesion defect) tests, diagnosed as
      autosomal recessive CGD. Based on the anamnesis, there was no known
      immunodeficiency history both in the case during neonatal period and her family
      members. Interferon-gamma therapy, which is recommended for the patients with CGD
      living in endemic areas, was initiated. Our patient's fever dropped at the 15th
      day of anti-tuberculosis treatment, and she was discharged on the 35th day and
      continued to receive treatment at home. The patient was followed up at outpatient
      clinic and had no additional complaints; her hepatosplenomegaly was back to
      normal at the third month. As a result, since BCG vaccine is contraindicated in
      CGD carriers, newborns with a family history of CGD should be immunologically
      examined and BCG vaccine should be avoided until the results are obtained. In
      addition, newborns without a family history, diagnosed as disseminated
      mycobacterial infection following BCG vaccination, should be evaluated for an
      underlying immunodeficiency condition.

PMID- 26313289
TI  - [Primary Neisseria meningitidis conjunctivitis in a 14-month-old child].
AB  - Meningococcal conjunctivitis is a rare but important infection since it can lead
      to severe complications and can threaten public health. It may emerge in two
      forms, either primary or secondary type which is developed after a systemic
      infection. Accurate diagnosis of primary meningococcal conjunctivitis is very
      important in addition to ocular complications which can result in loss of vision,
      the condition can also lead to severe complications like systemic meningococcal
      disease. However, the lack of specific symptoms which can distinguish
      meningococcal conjunctivitis from other forms of bacterial conjunctivitis,
      initiation of empiric antibiotic therapy without performing culture and
      nonaccurate differentiation of Neisseria gonorrhoeae and Neisseria meningitidis
      with commercial kits/systems used in laboratories cause problematic situations.
      This report describes a case of primary unilateral conjunctivitis in a 14-month
      old girl caused by non-groupable N.meningitidis that was resolved without
      sequelae following treatment. A pre-healthy 14-month-old girl was brought to the
      pediatric emergency department with redness, crusts and discharge in the left eye
      that had begun two days earlier. Ocular examination revealed hyperemia and
      purulent discharge in the left conjunctiva. Purulent conjunctivitis was
      diagnosed. A conjunctival swab specimen was taken for culture, and the patient
      was started on topical netilmicin (4x1), topical fusidic acid (2x1) and
      artificial tears. Microscopic examination of the conjunctival swab revealed
      polymorphonuclear leukocytes and no visible bacteria. Catalase and oxidase
      positive, gram-negative diplococci grew purely in culture. The first Gram stain
      preparation was evaluated again after the growth and small numbers of gram
      negative diplococci were observed. The cultivated bacteria were identified as
      N.meningitidis using MALDI-TOF MS (Bruker Daltonics, Germany), but as
      N.gonorrhoeae with BBL Crystal N/H (Neisseria/Haemophilus) (BD Diagnostic
      Systems, MD) identification system. The isolate was identified as N.meningitidis
      by polymerase chain reaction method. The isolate was sent to the Public Health
      Institution of Turkey for confirmation and serotyping. It was confirmed as non
      groupable N.meningitidis. This is the first report of conjunctivitis caused by
      non-groupable N.meningitidis from Turkey. We wish to emphasize the importance of
      Gram staining and differentiation of the species by automatized systems in
      diagnosis, netilmicin may be one of the options for empiric treatment and in
      terms of public health the most appropriate approach may be evaluation of the
      severity of conjunctivitis and causative serogroup which depends on case-based
      approach. 

PMID- 26313290
TI  - Response to "Different forms of intuitions".

PMID- 26313291
TI  - Hepatitis B surface antigen quantification as a predictor of seroclearance during
      treatment in HIV-hepatitis B virus coinfected patients from Sub-Saharan Africa.
AB  - BACKGROUND AND AIM: In Sub-Saharan Africa, seroclearance of hepatitis B surface
      antigen (HBsAg) and hepatitis B "e" antigen (HBeAg), including their quantifiable
      markers, have rarely been evaluated during long-term antiviral treatment among
      patients coinfected with HIV and hepatitis B virus (HBV). METHODS: In this
      prospective cohort study from two randomized-control trials in Cote d'Ivoire, 161
      antiretroviral-naive HIV-HBV coinfected patients starting lamivudine (n = 76) or
      tenofovir/emtricitabine (n = 85) containing antiretroviral therapy were included.
      HBV DNA was quantified using an in-house assay (detection limit = 12 copies/mL)
      and HBsAg quantification (qHBsAg) using the Elecsys assay. RESULTS: Overall, 33
      (20.5%) patients were HBeAg positive, 121 (75.2%) had detectable HBV DNA, and
      92/93 (98.9%) harbored HBV genotype E. Median treatment duration was 35.5 months
      (interquartile range: 24.3-36.4). Among HBeAg-positive patients, cumulative
      proportion with HBeAg seroclearance was 46.3% (n = 14). Overall, cumulative
      proportion of HBsAg seroclearance was 6.6% (n = 10). Lower baseline qHBsAg levels
      and strong 12-month declines in qHBsAg were significantly associated with HBsAg
      seroclearance for both HBeAg-negative and HBeAg-positive patients. When taken at
      certain levels, these determinants provided moderate sensitivity (Se) and
      specificity (Sp) in predicting HBsAg seroclearance at month 36 (<= 1000 IU/mL at
      baseline, Se = 0.80, Sp = 0.80; >= 1.0 log10  IU/mL drop at month 12, Se = 0.57,
      Sp = 1.00). Instead, qHBsAg levels <= 100 or <= 10 IU/mL at month 12 were optimal
      (both Se = 0.90 and Sp = 1.00). Detectable HBV-DNA provided fairly high Se and Sp
      when evaluated at baseline (Se = 1.00, Sp = 0.80), but not at month 12 (Se =
      0.80, Sp = 0.40). CONCLUSIONS: HBsAg seroclearance rates are not common in
      patients from Sub-Saharan Africa treated with anti-HBV containing antiretroviral
      therapy. qHBsAg levels at 12 months of treatment may accurately predict HBsAg
      seroclearance.

PMID- 26313292
TI  - Photokinetic Drug Delivery: Light-Enhanced Permeation in an In Vitro Eye Model.
AB  - PURPOSE: To investigate light-enhanced molecular movement as a potential
      technology for drug delivery. To do this, we developed an in vitro eye model
      while representing similar concentration gradient conditions and compositions
      found in the eye. METHODS: The eye model unit was fabricated by inserting a cross
      linked type I collagen membrane in a spectrophotometer cuvette with 1% hyaluronic
      acid as the drug recipient medium. Photokinetic delivery was studied by
      illuminating 1 mg/mL methotrexate (MTX) placed in the drug donor compartment on
      top of the membrane, with noncoherent 450 nm light at 8.2 mW from an LED source
      pulsed at 25 cycles per second, placed in contact with the solution. A modified
      UV-visual spectrophotometer was employed to rapidly determine the concentration
      of MTX, at progressive 1 mm distances away from the membrane, within the viscous
      recipient medium of the model eye after 1 h. RESULTS: A defined, progressive
      concentration gradient was observed within the nonagitated drug recipient media,
      diminishing with greater distances from the membrane. Transport of MTX through
      the membrane was significantly enhanced (ranging from 2 to 3 times, P < 0.05 to P
      <= 0.001) by photokinetic methods compared with control conditions by determining
      drug concentrations at 4 defined distances from the membrane. According to
      scanning electron microscopy images, no structural damage or shunts were created
      on the surface of the cross-linked gelatin membrane. CONCLUSION: The application
      of pulsed noncoherent visible light significantly enhances the permeation of MTX
      through a cross-linked collagen membrane and hyaluronic acid recipient medium
      without causing structural damage to the membrane.

PMID- 26313294
TI  - Value-Based Cancer Care and the Excessive Cost of Drugs.

PMID- 26313293
TI  - Multiple Anesthetic Exposure in Infant Monkeys Alters Emotional Reactivity to an
      Acute Stressor.
AB  - BACKGROUND: Retrospective studies in humans have shown a higher prevalence of
      learning disabilities in children that received multiple exposures to general
      anesthesia before the age of 4 yr. Animal studies, primarily in rodents, have
      found that postnatal anesthetic exposure causes neurotoxicity and neurocognitive
      deficits in adulthood. The authors addressed the question of whether repeated
      postnatal anesthetic exposure was sufficient to cause long-term behavioral
      changes in a highly translationally relevant rhesus monkey model, allowing study
      of these variables against a background of protracted nervous system and
      behavioral development. METHODS: Rhesus monkeys of both sexes underwent either
      three 4-h exposures to sevoflurane anesthesia (anesthesia group n = 10) or brief
      maternal separations (control group n = 10) on postnatal day 6 to 10 that were
      repeated 14 and 28 days later. Monkeys remained with their mothers in large
      social groups at all times except for overnight observation after each
      anesthetic/control procedure. At 6 months of age, each monkey was tested on the
      human intruder paradigm, a common test for emotional reactivity in nonhuman
      primates. RESULTS: The frequency of anxiety-related behaviors was significantly
      higher in monkeys that were exposed to anesthesia as neonates as compared with
      controls: anesthesia 11.04 +/- 1.68, controls 4.79 +/- 0.77, mean +/- SEM across
      all stimulus conditions. CONCLUSION: Increased emotional behavior in monkeys
      after anesthesia exposure in infancy may reflect long-term adverse effects of
      anesthesia.

PMID- 26313295
TI  - Effect of rescue surgery after non-curative endoscopic resection of early gastric
      cancer.
AB  - BACKGROUND: Whether rescue surgery confers a survival benefit in patients
      undergoing non-curative endoscopic resection of early gastric cancer remains
      controversial. METHODS: This was a retrospective review of patients who underwent
      non-curative endoscopic resection of at least one lesion of differentiated-type
      early gastric cancer between 2000 and 2011. Patients with a positive lateral
      resection margin as the only non-curative factor were excluded. Outcome was
      investigated by univariable (Kaplan-Meier) and multivariable (Cox proportional
      hazards) analysis. RESULTS: Some 341 patients underwent non-curative endoscopic
      resection for at least one lesion of differentiated-type early gastric cancer.
      Sixty-seven patients with a positive lateral resection margin as the only non
      curative factor were excluded, leaving 274 patients for analysis; 194 had rescue
      surgery and 80 had no additional treatment. The median duration of follow-up was
      60.5 months. Patients who had rescue surgery were younger, had a lower Charlson
      co-morbidity index score, smaller tumours and a higher lymphovascular invasion
      rate than patients with no treatment. Among 194 patients who had rescue surgery,
      intragastric local residual tumours were found in ten (5.2 per cent) and lymph
      node metastases in 11 (5.7 per cent). Patients with lymph node metastasis were
      significantly older than those without metastasis; no other significant
      differences were found. Univariable analysis showed that patients aged less than
      65 years, those with a Charlson co-morbidity index score below 4 and patients
      undergoing rescue surgery had significantly longer overall survival. Five-year
      overall survival rates in the rescue surgery and no-treatment groups were 94.3
      and 85 per cent respectively. In multivariable analysis, rescue surgery was
      identified as the only independent predictor of overall survival after non
      curative endoscopic resection of early gastric cancer. CONCLUSION: Rescue surgery
      confers a survival benefit after non-curative endoscopic resection of early
      gastric cancer.

PMID- 26313296
TI  - Herbicide Persistence in Seawater Simulation Experiments.
AB  - Herbicides are detected year-round in marine waters, including those of the World
      Heritage listed Great Barrier Reef (GBR). The few previous studies that have
      investigated herbicide persistence in seawater generally reported half-lives in
      the order of months, and several studies were too short to detect significant
      degradation. Here we investigated the persistence of eight herbicides commonly
      detected in the GBR or its catchments in standard OECD simulation flask
      experiments, but with the aim to mimic natural conditions similar to those found
      on the GBR (i.e., relatively low herbicide concentrations, typical temperatures,
      light and microbial communities). Very little degradation was recorded over the
      standard 60 d period (Experiment 1) so a second experiment was extended to 365 d.
      Half-lives of PSII herbicides ametryn, atrazine, diuron, hexazinone and
      tebuthiuron were consistently greater than a year, indicating high persistence.
      The detection of atrazine and diuron metabolites and longer persistence in
      mercuric chloride-treated seawater confirmed that biodegradation contributed to
      the breakdown of herbicides. The shortest half-life recorded was 88 d for growth
      regulating herbicide 2,4-D at 31 degrees C in the dark, while the fatty acid
      inhibitor metolachlor exhibited a minimum half-life of 281 d. The presence of
      moderate light and elevated temperatures affected the persistence of most of the
      herbicides; however, the scale and direction of the differences were not
      predictable and were likely due to changes in microbial community composition.
      The persistence estimates here represent some of the first appropriate data for
      application in risk assessments for herbicide exposure in tropical marine
      systems. The long persistence of herbicides identified in the present study helps
      explain detection of herbicides in nearshore waters of the GBR year round. Little
      degradation of these herbicides would be expected during the wet season with
      runoff and associated flood plumes transporting a high proportion of the original
      herbicide from rivers into the GBR lagoon. 

PMID- 26313297
TI  - Second Harmonic Generation Imaging Analysis of Collagen Arrangement in Human
      Cornea.
AB  - PURPOSE: To describe the horizontal arrangement of human corneal collagen bundles
      by using second harmonic generation (SHG) imaging. METHODS: Human corneas were
      imaged with an inverted two photon excitation fluorescence microscope. The
      excitation laser (Ti:Sapphire) was tuned to 850 nm. Backscatter signals of SHG
      were collected through a 425/30-nm bandpass emission filter. Multiple,
      consecutive, and overlapping image stacks (z-stacks) were acquired to generate
      three dimensional data sets. ImageJ software was used to analyze the arrangement
      pattern (irregularity) of collagen bundles at each image plane. RESULTS: Collagen
      bundles in the corneal lamellae demonstrated a complex layout merging and
      splitting within a single lamellar plane. The patterns were significantly
      different in the superficial and limbal cornea when compared with deep and
      central regions. Collagen bundles were smaller in the superficial layer and
      larger in deep lamellae. CONCLUSIONS: By using SHG imaging, the horizontal
      arrangement of corneal collagen bundles was elucidated at different depths and
      focal regions of the human cornea.

PMID- 26313298
TI  - The Relationship Between Visual Acuity and the Reproducibility of Visual Field
      Measurements in Glaucoma Patients.
AB  - PURPOSE: The purpose of this study was to investigate the association between
      visual acuity (VA) and reproducibility of test-retest visual field (VF)
      measurements in glaucoma patients. METHODS: Subjects were comprised of 627 eyes
      of 627 open-angle glaucoma patients. The reproducibility of two Humphrey VFs (24
      2 or 30-2 Swedish Interactive Threshold Algorithm tests) examined twice within
      the period of 3 months was calculated using the root mean squared error (RMSE) of
      each VF test point's sensitivity. Visual acuity was measured once at the time of
      either of the VF measurements. Linear modeling was used to investigate the
      relationship between reproducibility of VF tests (RMSE) and the following
      variables: mean total deviation value (mTD), fixation losses (FLs), false
      positives (FPs), false negatives (FNs), refractive error, age, and VA. RESULTS:
      The optimal model to predict test-retest variability (RMSE) of VFs included age,
      VA, mTD, and FNs as dependent variables. Root mean squared error was
      significantly larger in eyes with logMAR VA > 0.5 than in eyes with logMAR VA <=
      0. CONCLUSIONS: Reproducibility of VF tests becomes poor with the deterioration
      of VA. Careful consideration is needed when a patient's logMAR VA exceeds 0.5.

PMID- 26313299
TI  - The Reliability and Reproducibility of Corneal Confocal Microscopy in Children.
AB  - PURPOSE: To assess the image and patient level interrater agreement and
      repeatability within 1 month for corneal nerve fiber length (CNFL) measured using
      in vivo corneal confocal microscopy (IVCCM) in children. METHODS: Seventy-one
      subjects (mean [SD] age 14.3 [2.6] years, range 8-18 years; 44 with type 1
      diabetes and 27 controls; 36 males and 35 females) were included. 547 images (~6
      images per subject) were analyzed manually by two independent and masked
      observers. One-month repeat visit images were analyzed by a single masked
      observer in 21 patients. Automated image analysis was then performed using a
      specialized computerized software (ACCMetrics). RESULTS: For CNFL, the ICC (95%
      CI) were 0.94 (0.93-0.95) for image-level, 0.86 (0.78-0.91) for patient-level,
      and 0.88 (0.72-0.95) for the 1-month repeat assessment, and the Bland-Altman
      plots showed minimal bias between observers. Although there was excellent
      agreement between manual and automated analysis according to an ICC 0.89 (0.82
      0.93), the Bland-Altman plot showed a consistent bias with manual measurements
      providing higher readings. CONCLUSIONS: In vivo corneal confocal microscopy image
      analysis shows good reproducibility with excellent intraindividual and
      interindividual variability in pediatric subjects. Since the image-level
      reproducibility is stronger than the patient-level reproducibility, refinement of
      the method for image selection will likely further increase the robustness of
      this novel, rapid, and noninvasive approach to detect early neuropathy in
      children with diabetes. Further studies on the use of IVCCM to identify early
      subclinical neuropathy in children are indicated.

PMID- 26313300
TI  - Neuroprotective Effects of Human Serum Albumin Nanoparticles Loaded With
      Brimonidine on Retinal Ganglion Cells in Optic Nerve Crush Model.
AB  - PURPOSE: We investigated the neuroprotective effect of human serum albumin
      nanoparticles (HSA-NPs) and their conjugation with brimonidine (HSA-Br-NPs) on
      retinal ganglion cells (RGCs) in optic nerve crush (ONC) model. METHODS: We
      fabricated HSA-Br-NPs by ethanol precipitation, including 0.18% brimonidine (Br)
      and 3.5% human serum albumin (HSA) in HSA-Br-NP solution. We performed ONC and
      intravitreal injection in Sprague-Dawley rats, which were divided into (1)
      Normal, (2) balanced salt solution (BSS)-injected ONC, (3) HSA-NP-injected ONC,
      (4) Br-injected ONC, and (5) HSA-Br-NP-injected ONC groups. Survival of RGC was
      compared 5 and 14 days after procedures. A cell viability assay evaluated the
      amyloid-beta (Abeta)-associated neuroprotective mechanism of HSA-NP. RESULTS: The
      HSA-Br-NPs showed a narrow size distribution (152.8 +/- 51.1 nm) and a negatively
      charged surface (-29.7 +/- 7.5 mV), releasing Br for 5 days. The percentages of
      RGC survival in the HSA-NP (52.6 +/- 3.3%), Br (58.0 +/- 4.2%), and HSA-Br-NP
      (63.5 +/- 7.1%) groups relative to Normal (100%) were significantly higher than
      in the BSS group (29.2 +/- 3.3%) 5 days after ONC (P < 0.001). However, the HSA
      Br-NP (38.1 +/- 3.6%) group showed significantly higher RGC density than the BSS
      (10.3 +/- 5.6%, P < 0.001) or Br (18.6 +/- 3.9%, P = 0.006) group at 14 days. The
      HSA-NP injection reduced Abeta deposition in the RGC layer of ONC model, and a
      cell viability test showed that HSA-NP can inhibit Abeta-induced RGC death.
      CONCLUSIONS: Human serum albumin nanoparticles showed neuroprotective potential
      by inhibiting Abeta deposition, and exerted a sustained therapeutic effect with
      the combined neuroprotective agent. Our results suggest the potential of HSA-Br
      NP as a promising neuroprotective agent.

PMID- 26313301
TI  - Analysis of Changes in Refraction and Biometry of Atropine- and Placebo-Treated
      Eyes.
AB  - PURPOSE: To analyze changes in refraction and associated biometric changes in
      atropine- and placebo-treated eyes in the Atropine for Treatment of Myopia study
      (ATOM1). METHODS: A total of 400 myopic children, aged 6 to 12 years, were
      assigned randomly to receive 1% atropine or a placebo agent in one eye daily for
      2 years, after which drops were stopped and children monitored for another year.
      Cycloplegic autorefraction, A-scan biometry, and automated keratometry were
      performed at the initial visit, 2 weeks (baseline), and at 4, 8, 12, 16, 20, 24,
      30, and 36 months. RESULTS: A total of 313 children (78.3%) completed the study.
      In placebo-treated eyes, there was myopic progression of -1.55 diopters (D),
      between baseline and 36 months, associated with reductions in corneal curvature
      (K; -0.13 D) and anterior chamber depth (ACD; -0.17 mm) and increases in lens
      thickness (LT; 0.05 mm), vitreous chamber depth (VCD; 0.65 mm), and axial length
      (AL; 0.53 mm). Multivariate analysis of change in spherical equivalent
      demonstrated that the hyperopic shift (0.20 D) noted in atropine-treated eyes
      between baseline and 4 months, and the myopic rebound (-0.74 D) noted between 24
      to 30 months when atropine was stopped, were associated with a reduction and
      increase in VCD and AL, respectively, after adjusting for age and sex. Changes in
      K, ACD, and LT were less relevant. Between 4 and 24 months, atropine-treated eyes
      demonstrated gradual myopic progression (-0.40 D), accompanied by reduction in K
      (-0.06 D) and ACD (-0.07 mm) and increase in VCD (0.13 mm) and AL (0.06 mm).
      CONCLUSIONS: Atropine appeared to slow myopia progression mainly by reducing or
      slowing the growth in VCD, and thereby AL. (ClinicalTrials.gov number,
      NCT00371124.)

PMID- 26313303
TI  - Diagnosis of Early-Stage Glaucoma by Grid-Wise Macular Inner Retinal Layer
      Thickness Measurement and Effect of Compensation of Disc-Fovea Inclination.
AB  - PURPOSE: To evaluate grid-wise analyses of macular inner retinal layer
      thicknesses and effect of compensation of disc-fovea inclination for diagnosing
      early-stage glaucoma. METHODS: Spectral-domain optical coherence tomography
      measurements over a 6.0 * 6.0-mm macular area were prospectively obtained in 104
      eyes of 104 patients with early-stage glaucoma with a mean deviation of -1.8 +/-
      1.9 dB and 104 eyes of 104 age- and refraction-matched normal subjects. Macular
      retinal nerve fiber layer (mRNFL), ganglion cell-inner plexiform layer (GCIPL)
      combined, and ganglion cell complex (GCC) thickness of the entire area and each
      subdivided macular grid were determined to compare diagnostic capability for
      glaucoma using receiver operating characteristic curves and various normal cutoff
      values for each layer thickness and number of grids flagged as abnormal.
      Diagnostic capability was then compared with that of circumpapillary RNFL
      (cpRNFL) measurements. Effects of compensation of inclination of disc-fovea line
      by reconfiguration of the macular grid were also studied. RESULTS: Macular inner
      retinal layer analyses using 8 * 8 grids generally yielded higher diagnostic
      capability. Only the 8 * 8 grid GCC analyses using the various normal cutoff
      values yielded a sensitivity >= 0.90 with specificity >= 0.95 under several
      conditions in discriminating the glaucoma eyes. In glaucoma and normal eyes with
      both reliable cpRNFL and macular measurements, the best sensitivity/specificity
      were 0.98/0.95 for the 8 * 8 grid-mRNFL analysis and 0.93/0.96 for the 8 * 8 grid
      GCC analysis using various normal cutoff values, which were better than that
      (0.78/0.95) for clock-hour cpRNFL analysis (P = 0.001). Compensation of the disc
      fovea inclination did not improve the diagnostic capability. CONCLUSIONS: Grid
      wise analysis of macular GCC--especially using 8 * 8 grids and normative data
      based cutoff values--was very useful for diagnosing early-stage glaucoma, though
      compensation of the disc-fovea inclination had little effect.

PMID- 26313302
TI  - Hic-5 Regulates Actin Cytoskeletal Reorganization and Expression of Fibrogenic
      Markers and Myocilin in Trabecular Meshwork Cells.
AB  - PURPOSE: To explore the role of inducible focal adhesion (FA) protein Hic-5 in
      actin cytoskeletal reorganization, FA formation, fibrogenic activity, and
      expression of myocilin in trabecular meshwork (TM) cells. METHODS: Using primary
      cultures of human TM (HTM) cells, the effects of various external factors on Hic
      5 protein levels, as well as the effects of recombinant Hic-5 and Hic-5 small
      interfering RNA (siRNA) on actin cytoskeleton, FAs, myocilin, alpha-smooth muscle
      actin (alphaSMA), and collagen-1 were determined by immunofluorescence and
      immunoblot analyses. RESULTS: Hic-5 distributes discretely to the FAs in HTM
      cells and throughout the TM and Schlemm's canal of the human aqueous humor (AH)
      outflow pathway. Transforming growth factor-beta2 (TGF-beta2), endothelin-1,
      lysophosphatidic acid, hydrogen peroxide, and RhoA significantly increased Hic-5
      protein levels in HTM cells in association with reorganization of actin
      cytoskeleton and FAs. While recombinant Hic-5 induced actin stress fibers, FAs,
      alphav integrin redistribution to the FAs, increased levels of alphaSMA, collagen
      1, and myocilin, Hic-5 siRNA suppressed most of these responses in HTM cells. Hic
      5 siRNA also suppressed TGF-beta2-induced fibrogenic activity and dexamethasone
      induced myocilin expression in HTM cells. CONCLUSIONS: Taken together, these
      results reveal that Hic-5, whose levels were increased by various external
      factors implicated in elevated intraocular pressure, induces actin cytoskeletal
      reorganization, FAs, expression of fibrogenic markers, and myocilin in HTM cells.
      These characteristics of Hic-5 in TM cells indicate its importance in regulation
      of AH outflow through the TM in both normal and glaucomatous eyes.

PMID- 26313304
TI  - Comparing the Hem- and Lymphangiogenic Profile of Conjunctival and Uveal Melanoma
      Cell Lines.
AB  - PURPOSE: Malignant melanomas of the ocular surface (conjunctival melanoma [CM])
      and within the eye (uveal melanoma [UM]) show different types of metastatic
      behavior. While CM has a propensity to spread first to regional lymph nodes, UM
      metastasizes almost exclusively via the hematogenic route to the liver. We
      investigated whether these different metastatic patterns might be attributable to
      differential hem- and lymphangiogenic characteristics of CM and UM cells.
      METHODS: Human CM (CM2005.1, CRMM1, CRMM2) and UM (Mel270, Mel290, OM431) cell
      lines were analyzed for VEGF-A, -C, and -D expression by RT-PCR and ELISA. The
      influence of CM- or UM-conditioned medium on blood (BEC) and lymphatic (LEC)
      endothelial cell proliferation and migration was measured using 3-[4,5
      dimethylthiazol-2yl]-2,5-diphenyl-tetrazolium bromide (MTT) and scratch assays,
      respectively. RESULTS: Vascular endothelial growth factor-A, -C and -D mRNA, and
      VEGF-A and -D protein were expressed by all CM and UM cell lines, while VEGF-C
      protein was only expressed by UM cell lines. The CM- and UM-conditioned medium
      did neither differentially affect BEC (P = 0.86) and LEC (P = 0.90)
      proliferation, nor BEC (P = 0.56) and LEC (P = 0.90) migration. CONCLUSIONS:
      Conjunctival melanoma cell lines did not show a higher prolymphangiogenic
      potential, and UM cell lines did not show a higher prohemangiogenic potential.
      Accordingly, other mechanisms within the tumor microenvironment might account for
      the diverging metastatic patterns of conjunctival versus uveal melanomas.

PMID- 26313305
TI  - Metabolomic Analysis of Human Vitreous in Rhegmatogenous Retinal Detachment
      Associated With Choroidal Detachment.
AB  - PURPOSE: Our aim was to identify obvious different metabolites and metabolic
      pathways to elucidate the etiology of rhegmatogenous retinal detachment
      associated with choroidal detachment (RRDCD) so as to provide direction toward
      diagnosis and treatment of RRDCD. METHODS: We used a liquid chromatography
      quadrupole-time-of-flight/mass spectrometer (LC-Q-TOF/MS) to obtain the
      metabolome from the vitreous tissue of patients with rhegmatogenous retinal
      detachment (RRD) and RRDCD. The metabolomes from 29 samples (14 from RRD patients
      and 15 from RRDCD patients) were analyzed by principal component analysis (PCA)
      and partial least squares discriminant analysis (PLS-DA). A one-way analysis of
      variance with a Bonferroni correction was used to test significance. The Biofluid
      Metabolites Database and Human Metabolome Database were used to identify ions.
      RESULTS: The PLS-DA identified 265 (variable importance in the project >1) ions
      whose levels were significantly different in vitreous from patients with RRD and
      RRDCD. Among the 265 ions, 24 (23 observed in the positive mode and 1 observed in
      the negative mode) were identified by searching MS and MS/MS fragments in the
      Biofluid Metabolites Database and Human Metabolome Database. Metabolites found
      were associated with pathways related to proliferation, inflammatory reactions,
      and hemodynamic changes. CONCLUSIONS: Metabolites have been identified that were
      present in vitreous at significantly different levels between RRDCD and RRD.
      These metabolites are likely to be involved in the pathology of each disease and
      may potentially be used to diagnose and treat RRDCD and RRD.

PMID- 26313306
TI  - Does Myopia Affect Angle Closure Prevalence.
AB  - PURPOSE: To conduct a simulation study to estimate the prevalence of occludable
      angle (OA), a surrogate for primary angle closure glaucoma (PACG), with the
      increased rate of myopia in the Chinese population. METHODS: People with phakic
      eyes in Liwan Eye Study were included as the study sample. Anterior chamber depth
      (ACD) was measured before dilation by A-mode ultrasound and OA was evaluated with
      static gonioscopy. Random sampling was used to generate 50 cohorts with sample
      size of 200 for each of myopic rates 10%, 20%, 40%, 50%, and 135 for myopic rate
      60%, according to the multinomial distribution. The mean ACD and OA rates of each
      cohort were calculated. Logistic function model of nonlinear least-squares
      estimation was used to predict the prevalence of OA. RESULTS: Data of the right
      eyes from 1160 subjects were qualified for analysis. The mean age was 64.2 +/-
      9.5 years, with 43% being male. The prevalence of myopia and OA was 32.5% (95%
      confidence interval [CI], 29.8%-35.3%) and 10.3% (95% CI, 8.7%-12.2%),
      respectively. The mean ACD in the sampling cohorts increased from 2.68 mm to 2.74
      mm when the prevalence of myopia increased from 10% to 60%. The projected
      prevalence of OA in the cohorts with myopia prevalence of 10%, 20%, 40%, 50%, and
      60% was 11.1% (95% CI, 10.5%-11.8%), 10.7% (95% CI, 10.1%-11.4%), 9.9% (95% CI,
      9.3%-10.5%), 9.3% (95% CI, 8.8%-9.9%), and 9.6% (95% CI, 8.9-10.3%),
      respectively. CONCLUSIONS: The increasing prevalence of myopia has minimal impact
      on the prevalence of OA.

PMID- 26313307
TI  - Physical activity and liver diseases.
AB  - Regular physical activity beneficially impacts the risk of onset and progression
      of several chronic diseases. However, research regarding the effects of
      exercising on chronic liver diseases is relatively recent. Most researchers
      focused on nonalcoholic fatty liver disease (NAFLD), in which increasing clinical
      and experimental data indicate that skeletal muscle crosstalking to the adipose
      tissue and the liver regulates intrahepatic fat storage. In this setting,
      physical activity is considered to be required in combination with calories
      restriction to allow an effective decrease of intrahepatic lipid component, and
      despite that evidence is not conclusive, some studies suggest that vigorous
      activity might be more beneficial than moderate activity to improve
      NAFLD/nonalcoholic steatohepatitis. Evidence regarding the effects of exercise on
      the risk of hepatocellular carcinoma is scarce; some epidemiological studies
      indicate a lower risk in patients regularly and vigorously exercising. In
      compensated cirrhosis, exercise acutely increases portal pressure, but in the
      longer term it has been proved safe and probably beneficial. Decreased aerobic
      capacity (VO2 ) correlates with mortality in patients with decompensated
      cirrhosis, who are almost invariably sarcopenic. In these patients, VO2 is
      improved by physical activity, which might also reduce the risk of hepatic
      encephalopathy through an increase in skeletal muscle mass. In solid organ
      transplantation recipients, exercise is able to improve lean mass, muscle
      strength, and, as a consequence, aerobic capacity. Few data exist in liver
      transplant recipients, in whom exercise should be an object of future studies
      given its high potential of providing long-term beneficial effects. CONCLUSIONS:
      Despite that evidence is far from complete, physical activity should be seen as
      an important part of the management of patients with liver disease in order to
      improve their clinical outcome.

PMID- 26313308
TI  - Radiation exposure to foetus and breasts from dental X-ray examinations: effect
      of lead shields.
AB  - OBJECTIVES: Dental radiography may involve situations where the patient is known
      to be pregnant or the pregnancy is noticed after the X-ray procedure. In such
      cases, the radiation dose to the foetus, though low, needs to be estimated.
      Uniform and widely used guidance on dental X-ray procedures during pregnancy are
      presently lacking, the usefulness of lead shields is unclear and practices vary.
      METHODS: Upper estimates of radiation doses to the foetus and breasts of the
      pregnant patient were estimated with an anthropomorphic female phantom in
      intraoral, panoramic, cephalometric and CBCT dental modalities with and without
      lead shields. RESULTS: The upper estimates of foetal doses varied from 0.009 to
      6.9 MUGy, and doses at the breast level varied from 0.602 to 75.4 MUGy. With lead
      shields, the foetal doses varied from 0.005 to 2.1 MUGy, and breast doses varied
      from 0.002 to 10.4 MUGy. CONCLUSIONS: The foetal dose levels without lead
      shielding were <1% of the annual dose limit of 1 mSv for a member of the public.
      Albeit the relative shielding effect, the exposure-induced increase in the risk
      of breast cancer death for the pregnant patient (based on the breast dose only)
      and the exposure-induced increase in the risk of childhood cancer death for the
      unborn child are minimal, and therefore, need for foetal and breast lead
      shielding was considered irrelevant. Most important is that pregnancy is never a
      reason to avoid or to postpone a clinically justified dental radiographic
      examination.

PMID- 26313309
TI  - Ag Nanoparticle-Grafted PAN-Nanohump Array Films with 3D High-Density Hot Spots
      as Flexible and Reliable SERS Substrates.
AB  - A facile fabrication approach of large-scale flexible films is reported, with one
      surface side consisting of Ag-nanoparticle (Ag-NP) decorated polyacrylonitrile
      (PAN) nanohump (denoted as Ag-NPs@PAN-nanohump) arrays. This is achieved via
      molding PAN films with ordered nanohump arrays on one side and then sputtering
      much smaller Ag-NPs onto each of the PAN-nanohumps. Surface-enhanced Raman
      scattering (SERS) activity of the Ag-NPs@PAN-nanohump array films can be improved
      by curving the flexible PAN film with ordered nanohump arrays during the Ag
      sputtering process to increase the density of the Ag-NPs on the sidewalls of the
      PAN-nanohumps. More 3D hot spots are thus achieved on a large-scale. The Ag
      NPs@PAN-nanohump array films show high SERS activity with good Raman signal
      reproducibility for Rhodamine 6G probe molecules. To trial their practical
      application, the Ag-NPs@PAN-nanohump array films are employed as SERS substrates
      for trace detection of trinitrotoluene and a congener of polychlorinated
      biphenyls. A lower detection limit of 10(-12) m and 10(-5) m can be achieved,
      respectively. Furthermore, the flexible Ag-NPs@PAN-nanohump array films can also
      be utilized as swabs to probe traces of methyl parathion on the surface of fruits
      such as apples. The as-fabricated SERS substrates therefore have promising
      potential for applications in rapid safety inspection and environmental
      protection. 

PMID- 26313310
TI  - Effect of vitamins C and E on insulin resistance in diabetes: a meta-analysis
      study.
AB  - BACKGROUND: Data regarding the effect of vitamin C (VC) and vitamin E (VE)
      supplementation on insulin resistance in type 2 diabetes mellitus (T2DM) are
      controversial. We aimed to systematically review the current data on this topic.
      MATERIALS AND METHODS: All randomized controlled trials (RCTs) conducted to
      assess the effect of VC and/or VE on insulin resistance in diabetes published in
      Google Scholar and PubMed web databases until January 2014 were included.
      Exclusion criteria were studies conducted in animal, type 1 DM, children or
      pregnant women. Main outcome measure was insulin resistance by homoeostasis model
      assessment (HOMA) index. According to degree of heterogeneity, fixed- or random
      effect model was employed by stata software (11.0). RESULTS: We selected 14 RCTs
      involving 735 patients with T2DM. VE or mixture-mode supplementation did not have
      any significant effect on HOMA with a standardized mean difference (SMD): 0.017,
      95% CI: -0.376 to 0.411 (P = 0.932); and SMD: -0.035, 95% CI: -0.634 to 0.025 (P
      = 0.070), respectively, by random-effect model. VC supplement alone did not
      improve insulin resistance with a SMD: -0.150, 95% CI: -0.494 to 0.194 (P =
      0.391), by fixed-effect model. Meta-regression test demonstrated that HOMA index
      may have not been influenced by the year of publication, dosage or duration of
      treatment. CONCLUSIONS: The sole intake of VC, VE or their combination with other
      antioxidants could not improve insulin resistance in diabetes.

PMID- 26313311
TI  - Star GK Bileaflet Mechanical Valve Prosthesis-Patient Mismatch after Mitral Valve
      Replacement: A Chinese Multicenter Clinical Study.
AB  - BACKGROUND: The aim of this study was to investigate the incidence and immediate
      and mid-term effects of heart valve prosthesis-patient mismatch (PPM) after
      mitral valve replacement using the GK bileaflet mechanical valve. MATERIAL AND
      METHODS: A total of 493 cases of mechanical mitral valve replacement were
      performed in the departments of cardiac surgery in 7 hospitals from January 2000
      to January 2008. The patients included 142 men and 351 women ages 21 to 67
      (average age, 48.75). The patients were followed for 3 years after surgery. The
      effective orifice area index (EOAI), <=1.2 cm2/m2, was detected during the follow
      up period and was defined as PPM. The patients were assigned to either the PPM
      group or the non-PPM group. Finally, the preoperative, perioperative and
      postoperative indexes of the 2 groups of patients were compared. RESULTS: A total
      of 157 patients had PPM 3 years after surgery. The incidence of PPM was 31.84%.
      Sixty-three patients in the PPM group received a 25-mm GK bileaflet valve
      (40.13%), 82 received a 27-mm valve (52.23%), and 12 (7.64%) received a 29-mm
      valve. There were significant differences in length of intensive care unit stay,
      duration of ventilator use, length of hospitalization, body surface area, EOAI,
      mean transmitral pressure gradient, and pulmonary artery pressure between the PPM
      and non-PPM group (P<0.05). There was a significant difference between
      preoperative and postoperative pulmonary artery pressures among non-PPM patients
      (P<0.05); however, there was no statistical difference in preoperative and
      postoperative pulmonary artery pressures among patients with PPM (P>0.05).
      CONCLUSIONS: PPM after mitral valve replacement influences postoperative
      hemodynamics. Thus, larger-sized GK bileaflet mechanical valves are often used to
      reduce the risk of PPM.

PMID- 26313312
TI  - Muslim communities learning about second-hand smoke: a pilot cluster randomised
      controlled trial and cost-effectiveness analysis.
AB  - BACKGROUND: In the United Kingdom, men of Bangladeshi and Pakistani origin have
      higher smoking rates than the general population. This makes non-smokers in their
      households more vulnerable to second-hand smoke (SHS) exposure than the general
      population. AIMS: The aim of this study was to investigate the feasibility of
      implementing and pilot testing the effectiveness and cost-effectiveness of a
      'Smoke-free Homes' (SFH) intervention in Islamic religious settings to encourage
      families of Bangladeshi and Pakistani origin to apply smoking restrictions in
      their homes. METHODS: We allocated Islamic religious settings (clusters) to
      either receive SFH-an educational intervention-or to a control arm. Within each
      cluster, we recruited households with at least one smoker and one non-smoker. SHS
      exposure among non-smokers was measured using salivary cotinine. RESULTS: Seven
      (50%) clusters were randomised to each trial arm. A total of 468 households were
      assessed for eligibility and 62% (n=289) were eligible, of which 74% (n=213)
      agreed to participate in the trial. Six of the seven intervention clusters
      delivered the intervention, and all clusters were retained throughout the trial.
      In all, 81% (n=172) of households provided data at follow-up. No evidence of a
      difference in log cotinine level was observed (adjusted mean difference -0.02,
      95% confidence interval (CI) -1.28-1.23, P=0.97) between the two trial arms. The
      direct mean cost of delivering the intervention was L18.18 per household (range
      L3.55-42.20). CONCLUSIONS: It was possible to recruit, randomise and retain
      Islamic religious settings and participant households. However, some of the
      original assumptions, in particular our ability to collect primary outcome data,
      need to be revisited before a definitive trial.

PMID- 26313313
TI  - Effects of myocardial perfusion abnormalities on the accuracy of left ventricular
      volume and ejection fraction measured by thallium-201 gated single-photon
      emission tomography: comparison with echocardiography as the reference standard.
AB  - BACKGROUND: We assessed the accuracy of left ventricular end-diastolic volume
      (EDV), end-systolic volume (ESV), and ejection fraction (EF) using quantitative
      gated single-photon emission computed tomography (QGS) in comparison with
      echocardiography as the reference standard. We also assessed the effects of total
      perfusion deficit (TPD) on the accuracy of QGS measurements. METHODS: A total of
      258 patients underwent single-photon emission computed tomography and
      transthoracic echocardiography within 4 weeks of each investigation for
      evaluating coronary artery disease. Patients were divided into four groups
      according to TPD scores. RESULTS: There were 138 patients with no/minimal TPD, 64
      patients with small TPD, 35 patients with middle TPD, and 21 patients with large
      TPD. There were good correlations and agreements in EDV (r=0.87, 0.90, 0.71, and
      0.94, respectively), ESV (r=0.92, 0.94, 0.79, and 0.94, respectively), and EF
      (r=0.61, 0.79, 0.61, and 0.83, respectively) between QGS and echocardiography in
      patients with any TPD. QGS significantly underestimated EDV and ESV in patients
      with no/minimal or small TPD, and significantly overestimated ESV in patients
      with large TPD. QGS significantly underestimated EF in patients with middle or
      large TPD. CONCLUSION: Our results suggest that QGS is a useful tool for
      assessing the left ventricular volume and function in patients with any TPD, but
      myocardial perfusion abnormalities should be taken into consideration when
      interpreting QRS measurements.

PMID- 26313314
TI  - The Swedish specialist examination in emergency medicine: form and function.
AB  - AIM/BACKGROUND: The purpose of the Swedish specialist examination in Emergency
      Medicine is not only to determine whether residents have attained the level of
      competence of specialists, but also to guide and facilitate residency training.
      METHODS: The Swedish Society for Emergency Medicine has developed checklists that
      delineate criteria of consideration and action items for particular processes.
      These checklists are freely available and used to assess competence during the
      examination. They are also intended for use during teaching and clinical care,
      thus promoting alignment between clinical practice, teaching and assessment. The
      examination is carried out locally by residency program educators, thereby
      obviating travel expenses. It consists of a total of 24 stations and over 100
      potential scenarios, thereby minimizing case specificity. Each station consists
      of a scenario based on a real case. The checklists allow for direct feedback to
      the examinee after each station. RESULTS AND CONCLUSION: This model may be of
      interest to other European countries.

PMID- 26313315
TI  - Number of organ dysfunctions predicts mortality in emergency department patients
      with suspected infection: a multicenter validation study.
AB  - OBJECTIVES: The aim of this study was to validate the association between number
      of organ dysfunctions and mortality in emergency department (ED) patients with
      suspected infection. METHODS: This study was conducted at two medical care center
      EDs. The internal validation set was a prospective cohort study conducted in
      Boston, USA. The external validation set was a retrospective case-control study
      conducted in Aarhus, Denmark. The study included adult patients (>18 years) with
      clinically suspected infection. Laboratory results and clinical data were used to
      assess organ dysfunctions. Inhospital mortality was the outcome measure.
      Multivariate logistic regression was used to determine the independent mortality
      odds for number and types of organ dysfunctions. RESULTS: We enrolled 4952
      (internal) and 483 (external) patients. The mortality rate significantly
      increased with increasing number of organ dysfunctions: internal validation: 0
      organ dysfunctions: 0.5% mortality, 1: 3.6%, 2: 9.5%, 3: 17%, and 4 or more: 37%;
      external validation: 2.2, 6.7, 17, 41, and 57% mortality (both P<0.001 for
      trend). Age-adjusted and comorbidity-adjusted number of organ dysfunctions
      remained an independent predictor. The effect of specific types of organ
      dysfunction on mortality was most pronounced for hematologic [odds ratio (OR) 3.3
      (95% confidence interval (CI) 2.0-5.4)], metabolic [OR 3.3 (95% CI 2.4-4.6);
      internal validation], and cardiovascular dysfunctions [OR 14 (95% CI 3.7-50);
      external validation]. CONCLUSION: The number of organ dysfunctions predicts
      sepsis mortality.

PMID- 26313316
TI  - Tranexamic acid in major trauma: implementation and evaluation across South West
      England.
AB  - OBJECTIVE: To carry out a prospective evaluation of tranexamic acid (TXA) use in
      trauma patients. PATIENTS AND METHODS: TXA was introduced to all emergency
      ambulances and emergency departments in the South West, UK, on 1 December 2011.
      We carried out a prospective evaluation of TXA use in trauma patients in the
      South West Peninsula between December 2011 and December 2012. We collected
      prehospital and hospital data on TXA administration using the Trauma Audit
      Research Network database. Data on prehospital administration of TXA were cross
      checked with the South Western Ambulance Service Trust. Data were analysed using
      SPSS (version 20). RESULTS: Altogether, 82 patients were administered TXA during
      the study period. The median age of the patients was 49 years (IQR 30, 66), and
      72% were men. One-third of the patients arrived at hospital by air ambulance.
      During the first 3 months, administration of TXA was limited to one patient each
      month receiving the drug. However, an upward trend was observed after June until
      October 2012, with the increment being more than 10 fold in July, September and
      October 2012. CONCLUSION: This is the first study to evaluate the use of TXA in
      civilian practice in the UK. Our study shows that ambulance service personnel and
      emergency departments can effectively administer TXA.

PMID- 26313317
TI  - SODAS: Surveillance of Drugs of Abuse Study.
AB  - OBJECTIVE: Novel psychoactive substance (NPS) as a form of recreational drug use
      has become increasingly popular. There is a paucity of information with regard to
      the prevalence and clinical sequelae of these drugs. The aim of this study was to
      detect NPS in patients presenting to the emergency department with suspected
      toxicological ingestion. PATIENTS AND METHODS: The prospective study was
      performed in a large emergency department in the UK. During a 3-month period 80
      patients were identified by clinicians as having potentially ingested a
      toxicological agent. Urine samples were analysed using liquid chromatography high
      resolution mass spectrometry, and basic clinical data was gathered. RESULTS:
      Eighty patients with a history of illicit or recreational drug consumption had
      urine screenings performed. Forty-nine per cent (39) of the patients undergoing a
      screen had more than one illicit substance detected. Twenty per cent (16) of the
      patients tested positive for at least one NPS. CONCLUSION: Almost half of the
      presented patients revealed ingestion of multiple substances, which correlated
      poorly with self-reporting of patients. Developing enhanced strategies to monitor
      evolving drug trends is crucial to the ability of clinicians to deliver care to
      this challenging group of patients.

PMID- 26313318
TI  - Solvent-Mediated Crystallization of CH3NH3SnI3 Films for Heterojunction Depleted
      Perovskite Solar Cells.
AB  - Organo-lead halide perovskite solar cells have gained enormous significance and
      have now achieved power conversion efficiencies of ~20%. However, the potential
      toxicity of lead in these systems raises environmental concerns for widespread
      deployment. Here we investigate solvent effects on the crystallization of the
      lead-free methylammonium tin triiodide (CH3NH3SnI3) perovskite films in a
      solution growth process. Highly uniform, pinhole-free perovskite films are
      obtained from a dimethyl sulfoxide (DMSO) solution via a transitional SnI2.3DMSO
      intermediate phase. This high-quality perovskite film enables the realization of
      heterojunction depleted solar cells based on mesoporous TiO2 layer but in the
      absence of any hole-transporting material with an unprecedented photocurrent up
      to 21 mA cm(-2). Charge extraction and transient photovoltage decay measurements
      reveal high carrier densities in the CH3NH3SnI3 perovskite device which are one
      order of magnitude larger than CH3NH3PbI3-based devices but with comparable
      recombination lifetimes in both devices. The relatively high background dark
      carrier density of the Sn-based perovskite is responsible for the lower
      photovoltaic efficiency in comparison to the Pb-based analogues. These results
      provide important progress toward achieving improved perovskite morphology
      control in realizing solution-processed highly efficient lead-free perovskite
      solar cells. 

PMID- 26313319
TI  - Manipulation Under Anesthesia: A Safe and Effective Treatment for Posttraumatic
      Arthrofibrosis of the Knee.
AB  - OBJECTIVES: This study investigates the results of closed manipulations performed
      under anesthesia (MUA) to evaluate whether it is an effective means to treat
      posttraumatic knee arthrofibrosis. DESIGN: Retrospective review. SETTING: Level I
      trauma center. PATIENTS/PARTICIPANTS: Twenty-two patients with a mean age of 40
      underwent closed MUA for posttraumatic knee arthrofibrosis. Injuries included
      fractures of the femur, tibia, and patella as well as ligamentous injuries and
      traumatic arthrotomies. The mean time from treatment to manipulation was 90 days.
      Mean follow-up after manipulation was 7 months. INTERVENTION: Closed knee MUA.
      OUTCOME MEASUREMENTS: Improvement of knee range of motion (ROM) arc was the
      primary outcome. Patient demographics were correlated with manipulation success
      using a 2-sample t test. A delay in manipulation of 90 days or greater was also
      evaluated in this fashion with regard to its role in predicting the benefit of
      MUA. RESULTS: The mean premanipulation ROM arc was 59 +/- 25 degrees. The mean
      intraoperative arc of motion, achieved at the time of the manipulation was 123 +/
      14 degrees. No complications occurred during the MUA procedure. At the most
      recent follow-up, the mean ROM arc was 110 +/- 19 degrees. Tobacco use,
      associated injuries, elevated body mass index, open fracture, and advanced age
      did not impact manipulation efficacy. Additionally, manipulations performed 90
      days or more after surgical treatment provided a benefit equaling those performed
      more acutely (P = 0.12). DISCUSSION: MUA is a safe and effective method to
      increase knee ROM in the setting of posttraumatic arthrofibrosis. Improvement in
      ROM was noted in all patients. A 90-day window between fracture fixation and
      manipulation did not impact ROM at final follow-up and may prevent fracture
      displacement during the MUA. LEVEL OF EVIDENCE: Therapeutic Level IV. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 26313320
TI  - Surgical-site infection surveillance in cranial neurosurgery.
AB  - INTRODUCTION: Surgical-site infection (SSI) is associated with significant
      morbidity and mortality. Public Health England or PHE has published guidance on
      its surveillance, which is now mandatory in some specialities. We review how
      appropriate their programme is for monitoring SSI in cranial neurosurgery [CN].
      METHOD: SSI data on all patients [N = 2375] undergoing CN, over two years, at
      Salford Royal Foundation NHS Trust or SRFT were prospectively recorded. SSI was
      defined as arising within 30 days of operation or 1 year where an implant(s)
      remains. Follow-up, by a dedicated SSI nurse, was at 30 days using inpatient,
      outpatient clinic or telephone consultation, or post-discharge postal
      questionnaires [PDpQ] and by monitoring for readmissions. A descriptive analysis
      was performed looking at the follow-up process and SSI rate. RESULTS: Thirty-day
      follow-up data was obtained in 1776 patients (74.8%). Overall, 82 (3.5%) patients
      had a confirmed SSI. 22/82 (27%) were identified as inpatients [median time from
      operation: 14.5 days, inter-quartile range (IQR): 16] and 60/82 (73%) as
      readmissions [median time from operation: 31.5 days, IQR: 186.5]. No SSIs were
      identified via PDpQ. CONCLUSIONS: These data suggest that active outpatient
      follow-up is not necessary and that monitoring of inpatients and readmissions is
      enough for a cranial neurosurgical SSI programme.

PMID- 26313321
TI  - Plant MAPK cascades: Just rapid signaling modules?
AB  - Abscisic acid (ABA) is a major phytohormone mediating important stress-related
      processes. We recently unveiled an ABA-activated MAPK signaling module
      constituted of MAP3K17/18-MKK3-MPK1/2/7/14. Unlike classical rapid MAPK
      activation, we showed that the activation of the new MAPK module is delayed and
      relies on the MAP3K protein synthesis. In this addendum, we discuss the role of
      this original and unexpected activation mechanism of MAPK cascades which suggests
      that MAPKs can regulate both early and long-term plant stress responses. 

PMID- 26313322
TI  - The Effect of Metabolic Syndrome on the Success and Complications of Percutaneous
      Nephrolitotomy.
AB  - BACKGROUND: The aim of this study was to investigate the effect of Metabolic
      syndrome (MetS) on the success and complications of percutaneous nephrolithotomy
      (PNL). METHODS: Two hundred ten patients who had undergone PNL for kidney stones
      in our clinic between May 2012 and May 2014 were retrospectively analyzed. The
      patients were divided into two groups based on whether they had diagnostic
      criteria for MetS. All patients had lower pole kidney stones between 15 and 20
      mm. Complication rates between groups were evaluated using a modified Clavien
      grading system. RESULTS: Group1 was a standard PNL group and group 2 consisted of
      patients with MetS. Mean stone size was 293.25 +/- 102.4 mm(2) for group 1 and
      301.10 +/- 169.5 mm(2) for group 2 (p < 0.05). Mean hospitalization days,
      fluoroscopy duration, and mean hematocrit loss were significantly higher in group
      2. Mean operative time and need for blood transfusions were higher in group 2 but
      statistically insignificant. One hundred twenty five patients in group 1 (96.1%)
      and 72 patients in group 2 (90%) obtained stone-free state. CONCLUSIONS: Our
      study results reveal an increase in complications and morbidity for patients with
      MetS during PNL.

PMID- 26313323
TI  - Willingness of African American Women to Participate in e-Health/m-Health
      Research.
AB  - INTRODUCTION: Due to high rates of technology adoption, African American women
      are well positioned to benefit from e-health/mobile health (m-health)
      interventions; yet, there are limited data on understanding their use of
      technology and willingness to participate in e-health/m-health research.
      MATERIALS AND METHODS: A self-administered survey was completed by 589 African
      American women. Survey items measured sociodemographics, technology use and
      access, and willingness to participate in e-health/m-health research. Multinomial
      logistic regression examined associations among three age groups (18-29, 30-50,
      and 51+years old) and technology access, as well as motivators and barriers to
      participating in e-health/m-health research. RESULTS: Most participants were
      willing to receive text messages as part of a research study. Many reported using
      a health-related application in the past 30 days, with younger women more likely
      to do so than older women (p<0.0001). Younger women were more likely than older
      women to be motivated for the greater good (p<0.01) and for financial incentives
      (p=0.02), whereas older women were more likely than younger women to be motivated
      if referred by a healthcare provider (p=0.02). Younger women were more likely
      than older women to report concerns about data plans (p<0.01 for all), whereas
      older women were more likely to report a lack of a smartphone (p=0.048) and
      privacy concerns (p<0.001). CONCLUSIONS: Culturally tailored e-health/m-health
      research using smartphones may be of interest to African American women who are
      interested in risk reduction and chronic disease self-management. Barriers such
      as smartphone data plans and privacy will need to be addressed.

PMID- 26313325
TI  - Different forms of intuitions.

PMID- 26313324
TI  - Who Gets Early Tracheostomy?: Evidence of Unequal Treatment at 185 Academic
      Medical Centers.
AB  - BACKGROUND: Although the benefits of early tracheostomy in patients dependent on
      ventilators are well established, the reasons for variation in time from
      intubation to tracheostomy remain unclear. We identified clinical and demographic
      disparities in time to tracheostomy. METHODS: We performed a level 3
      retrospective prognostic study by querying the University HealthSystem Consortium
      (2007-2010) for adult patients receiving a tracheostomy after initial intubation.
      Time to tracheostomy was designated early (< 7 days) or late (> 10 days). Cohorts
      were stratified by time to tracheostomy and compared using univariate tests of
      association and multivariable adjusted models. RESULTS: A total of 49,191
      patients underwent tracheostomy after initial intubation: 42% early (n = 21,029)
      and 58% late (n = 28,162). On both univariate and multivariable analyses, women,
      blacks, Hispanics, and patients receiving Medicaid were less likely to receive an
      early tracheostomy. Patients in the early group also experienced lower rates of
      mortality (OR, 0.84; 95% CI, 0.79-0.88). CONCLUSIONS: Early tracheostomy was
      associated with increased survival. Yet, there were still significant disparities
      in time to tracheostomy according to sex, race, and type of insurance.
      Application of evidence-based algorithms for tracheostomy may reduce unequal
      treatment and improve overall mortality rates. Additional research into this
      apparent bias in referral/rendering of tracheostomy is needed.

PMID- 26313326
TI  - Classification of different patterns of pulmonary adenocarcinomas.
AB  - The epidemic increase of adenocarcinoma histology accounting for more than 50% of
      primary lung malignancies and the advent of effective molecular targeted
      therapies against specific gene alterations characterizing this tumor type have
      led to the reconsideration of the pathologic classification of lung cancer. The
      new 2015 WHO classification provided the basis for a multidisciplinary approach
      emphasizing the close correlation among clinical, radiologic and molecular
      characteristics and histopathologic pattern of lung adenocarcinoma. The terms
      'bronchioloalveolar carcinoma' and 'mixed adenocarcinoma' have been eliminated,
      introducing the concepts of 'adenocarcinoma in situ', 'minimally invasive
      adenocarcinoma' and the use of descriptive predominant patterns in invasive
      adenocarcinomas (lepidic, acinar, papillary, solid and micropapillary patterns).
      'Invasive mucinous adenocarcinoma' is the new definition for mucinous
      bronchioloalveolar carcinoma, and some variants of invasive adenocarcinoma have
      been included, namely colloid, enteric and fetal-type adenocarcinomas. A concise
      update of the immunomorphologic, radiological and molecular characteristics of
      the different histologic patterns of lung adenocarcinoma is reported here. 

PMID- 26313327
TI  - Risk of oral and gastrointestinal mucosal injury in patients with solid tumors
      treated with ramucirumab: a systematic review and meta-analysis.
AB  - BACKGROUND: We performed a systematic review and meta-analysis of the risk of
      oral and gastrointestinal (GI) mucosal injury associated with ramucirumab.
      PATIENTS AND METHODS: Eligible studies included randomized Phase II and III
      trials of patients with solid tumors on ramucirumab: describing events of
      stomatitis, diarrhea, GI perforation and GI hemorrhage. RESULTS: Our search
      strategy yielded 167 potentially relevant citations from Pubmed/Medline, CENTRAL
      Cochrane registry, European society of medical oncology meeting abstracts and
      American Society of Clinical Oncology meeting library. After exclusion of
      ineligible studies, a total of 11 clinical trials were considered eligible for
      the meta-analysis. The RR of all-grade stomatitis, diarrhea, GI perforation and
      GI hemorrhage were 1.62 (95% CI 1.31 - 2.00; p < 0.00001), 1.15 (95% CI 1.07 -
      1.24; p < 0.0001), 3.29 (95% CI 1.54 - 7.04; p = 0.002) and 1.92 (95% CI 1.03 -
      3.57; p = 0.04), respectively. The RR of high-grade stomatitis, diarrhea, GI
      perforation and GI hemorrhage were 2.72 (95% CI 1.76 - 4.19; p < 0.00001), 1.28
      (95% CI 0.96 - 1.71; p = 0.09), 3.37 (95% CI 1.51 - 7.54; p = 0.03) and 1.26 (95%
      CI 0.79 - 2.01; p = 0.34), respectively. CONCLUSIONS: Our meta-analysis has
      demonstrated that ramucirumab-based combination treatment is associated with an
      increased risk of high-grade stomatitis and GI perforation compared to control
      treatment.

PMID- 26313328
TI  - What automated age estimation of hand and wrist MRI data tells us about skeletal
      maturation in male adolescents.
AB  - BACKGROUND: Age estimation of individuals is important in human biology and has
      various medical and forensic applications. Recent interest in MR-based methods
      aims to investigate alternatives for established methods involving ionising
      radiation. Automatic, software-based methods additionally promise improved
      estimation objectivity. AIM: To investigate how informative automatically
      selected image features are regarding their ability to discriminate age, by
      exploring a recently proposed software-based age estimation method for MR images
      of the left hand and wrist. SUBJECTS AND METHODS: One hundred and two MR datasets
      of left hand images are used to evaluate age estimation performance, consisting
      of bone and epiphyseal gap volume localisation, computation of one age regression
      model per bone mapping image features to age and fusion of individual bone age
      predictions to a final age estimate. RESULTS: Quantitative results of the
      software-based method show an age estimation performance with a mean absolute
      difference of 0.85 years (SD = 0.58 years) to chronological age, as determined by
      a cross-validation experiment. Qualitatively, it is demonstrated how feature
      selection works and which image features of skeletal maturation are automatically
      chosen to model the non-linear regression function. CONCLUSION: Feasibility of
      automatic age estimation based on MRI data is shown and selected image features
      are found to be informative for describing anatomical changes during physical
      maturation in male adolescents.

PMID- 26313329
TI  - Centrosome separation; a careful balancing act.

PMID- 26313330
TI  - Concave or convex pi-dimers: the role of the pancake bond in substituted
      phenalenyl radical dimers.
AB  - pi-stacking in dimers of phenalenyl represents the prototypical pancake bonding
      between radicals. This type of pi-stacking aggregate is a key structural motif in
      conducting organic and multifunctional materials. It is driven by the bonding
      combination of the singly occupied molecular orbitals (SOMOs) of the monomers
      resulting in pi-stacking contacts that are significantly shorter than the sum of
      the van der Waals (vdW) radii. Analysis of 56 structures from the literature
      (mostly from the Cambridge Structural Database) coupled with DFT computations
      shows that the central CC contact in derivatives of phenalenyl does not
      contribute directly to the pi-stacking pancake bonding in accordance with the
      fact that the SOMO coefficient is zero at the central carbon. This central CC
      contact is typically longer than the contacts between the SOMO bearing alpha
      carbons with a convex dimer shape with one known exception of a complex
      containing bulky tert-butyl groups. This unusual case of a concave shaped dimer
      with a significantly shorter central CC contact is due to the steric repulsions
      at the periphery of the molecule pushing the central atoms closer together
      relative to the alpha-alpha-contacts which provide the attractive driving force
      for the multicenter pancake bonding. The diradical character of the pancake
      bonding is revealed by the analysis of the unpaired electron density based on
      high-level multireference theory. 

PMID- 26313331
TI  - The long-term outlook to final outcome and steroid treatment results in children
      with idiopathic nephrotic syndrome.
AB  - Idiopathic Nephrotic Syndrome (INS) was defined as combination of a nephrotic
      syndrome and non-specific histological abnormalities of the kidney. Among these
      abnormalities, minimal change nephrotic syndrome (MCNS) is the most common. We
      report our experience with MCNS; its clinical course, treatments and outcomes.
      One-hundred twenty children (66 male, 54 female) with MCNS, admitted to
      Nephrology Department between 1987-2009 was assessed. Their clinical
      presentations, treatment and disease courses were reviewed. The mean duration of
      follow-up was 11.5 +/- 1.9 years. Initially, all patients given prednisone 2
      mg/kg/ day single dose per four weeks a followed by eight weeks of the same daily
      dose given every other day. After week 12, prednisone was progressively tapered
      off at the rate of 0.5 mg/kg per 15 daily intervals until complete
      discontinuation had been achieved by week 16. Steroid resistance was accepted as
      no achievement of remission following four weeks of prednisone 2 mg/kg/day
      followed by three intravenous pulses of corticosteroids. At the end of the
      initial steroid treatment, 106 (88.3%) patients were determinate steroid
      responsive while 14 (11.7%) patients were steroid resistance. Thirty-eight
      patients underwent biopsy. At the end of study recovery rate was increased from
      88.3% to 94.1%. In conclusion, most of patients entered remission by our therapy
      end of follow up time. With the support of our satisfactory results among the
      whole study group, long-term prednisolone treatment still remains valid. 

PMID- 26313332
TI  - Comparison of Pituitary Adenomas in Elderly and Younger Adults: Clinical
      Characteristics, Surgical Outcomes, and Prognosis.
AB  - OBJECTIVES: To analyze and summarize the clinical characteristics, surgical
      outcomes, and prognosis of elderly adults with pituitary adenomas (PAs). DESIGN:
      Retrospective cohort study. SETTING: Tongji Hospital. PARTICIPANTS: Individuals
      who underwent transsphenoidal surgery for PAs between 2009 and 2012 (N = 1,104).
      MEASUREMENTS: Participants were divided into two age groups (>=65 and <65), and
      their clinical characteristics, surgical complications, surgical outcomes, and
      follow-up data were analyzed and compared. RESULTS: The older group had longer
      duration of symptoms. The most common symptom were mass effects (98.4%) in the
      older group and hormone-secreting effects (55.2%) in the younger group. The
      incidence of pituitary apoplexy (P = .03), incidentaloma (P = .03) and
      misdiagnosis at first visit (P < .001) were higher in the older group.
      Nonfunctioning PAs (P < .001) and giant adenomas (P = .04) were more common in
      the elderly group than in the younger group. There were no significant
      differences in the incidence of postoperative diabetes insipidus, cerebrospinal
      fluid (CSF) leak, regrowth, visual outcome, or permanent hypopituitarism between
      the groups (P > .05). The incidence of severe systemic complications was greater
      in the older group (3/69 vs 3/1,035, relative risk = 15.00, 95% confidence
      interval = 3.08-72.94, P = .004), and all three cases in the older group occurred
      after emergency surgery. The incidence of hypopituitarism before surgery and 3
      days after surgery was higher in the elderly group (P < .05). Older participants
      tended to have more difficulty recovering from preoperative hypopituitarism (P =
      .02). CONCLUSION: Avoiding misdiagnosis and emergency surgery is critical for
      frail elderly adults with multiple comorbidities. With early active management,
      sufficient preoperative preparation, and multidisciplinary collaboration, the
      long-term outcomes and prognosis of elderly adults with PAs are comparable with
      those of younger adults.

PMID- 26313333
TI  - Sensitive determination of plasma protein binding of cationic drugs using mixed
      mode solid-phase microextraction.
AB  - Freely dissolved concentrations are considered to be the most relevant
      concentration in pharmacology and toxicology, as they represent the active
      concentration available for interaction with its surroundings. Here, a solid
      phase microextraction (SPME) coating that combines octadecyl and propylsulfonic
      acid groups as strong cation exchange sites, known as C18/SCX or "mixed-mode"
      SPME, is used to measure freely dissolved concentrations of amitriptyline,
      amphetamine, diazepam and tramadol to different binding matrices, including
      bovine serum albumin (BSA), human serum albumin (HSA), human plasma and human
      whole blood. A potential confounding factor in binding studies is that proteins
      may sorb to the fiber coating leading to incorrect measurement of protein
      sorption or changes in uptake kinetics to the fiber coating. Sorption of bovine
      serum albumin (BSA) was observed and quantified using a Lowry assay. BSA binds to
      the C18/SCX fiber in small amounts, but large changes in uptake kinetics were not
      observed. All experiments were performed at equilibrium. In addition, however,
      the effect of depletion and non-equilibrium extraction on the estimation of
      protein binding affinities was also studied. Binding affinities to BSA and human
      serum albumin (HSA) were calculated as log KBSA or log KHSA. These values were
      very similar to reported literature values. Sampling at either equilibrium or non
      equilibrium resulted in similar binding affinities. Furthermore, SPME fibers were
      used to measure freely dissolved concentrations in undiluted human plasma and
      whole blood. Analysis of SPME extracts could be performed using HPLC-UV or HPLC
      with fluorescence detection without prior clean-up of the samples. Measured bound
      fractions in plasma using this SPME approach were comparable to literature
      reference values. Bound fractions in whole blood were always higher than in
      plasma, due to red blood cell partitioning. This work shows the potential of SPME
      as sampling tool for freely dissolved concentrations, especially for highly
      protein-bound compounds. Conventional SPME coatings such as polyacrylate (PA) or
      polydimethylsiloxane (PDMS) might be lacking sensitivity when sampling the small
      neutral fraction of highly protein-bound positively charged compounds, but the
      C18/SCX fiber is able to sorb the charged species of organic cations, thereby
      improving sensitivity for these types of compounds.

PMID- 26313335
TI  - Breast implant extrusion related to Herpesviridae.
AB  - INTRODUCTION: We present a case of wound dehiscence in a patient with clinical
      features of herpes zoster. PRESENTATION OF CASE: A 44 year old woman, with a
      history of recurrent herpes zoster infection, presented to the accident and
      emergency department with the extrusion of a left sided tear-drop shaped euro
      silicone breast implant from an old surgical scar. A month prior to admission,
      this patient had developed unilateral crops of vesicles along the surgical scar
      which was apposing her left infra-mammary fold. This was preceded by fatigue and
      neuralgia. Histology revealed acute inflammation related to a probable
      Herpesviridae infection. DISCUSSION: In this report we discuss the first case of
      a viral infection predisposing to a wound dehiscence occurring in an old surgical
      scar. CONCLUSION: This case report illustrates the real but rare possibility of
      recurrent herpes zoster causing gradual thinning of an old surgical scar. This
      resulted in an extrusion of the underlying breast implant.

PMID- 26313334
TI  - Decreased approach behavior and nucleus accumbens immediate early gene expression
      in response to Parkinsonian ultrasonic vocalizations in rats.
AB  - Many individuals with Parkinson disease (PD) have difficulty producing normal
      speech and voice, resulting in problems with interpersonal communication and
      reduced quality of life. Translational animal models of communicative dysfunction
      have been developed to assess disease pathology. However, it is unknown whether
      acoustic feature changes associated with vocal production deficits in these
      animal models lead to compromised communication. In rodents, male ultrasonic
      vocalizations (USVs) have a well-established role in functional inter-sexual
      communication. To test whether acoustic deficits in USVs observed in a PTEN
      induced putative kinase 1 (PINK1) knockout (KO) PD rat model compromise
      communication, we presented recordings of male PINK1 KO USVs and normal wild-type
      (WT) USVs to female rat listeners. We measured approached behavior and immediate
      early gene expression (c-Fos) in brain regions implicated in auditory processing
      and sexual motivation. Our results suggest that females show reduced approach in
      response to PINK1 KO USVs compared with WT. Moreover, females exposed to PINK1 KO
      USVs had lower c-Fos immunolabeling in the nucleus accumbens, a region implicated
      in sexual motivation. These results are the first to demonstrate that
      vocalization deficits in a rat PD model result in compromised communication.
      Thus, the PINK1 KO PD model may be valuable for assessing treatments aimed at
      restoring vocal communicative function. 

PMID- 26313336
TI  - Right gastro-omental artery reconstruction after pancreaticoduodenectomy for
      subtotal esophagectomy and gastric pull-up.
AB  - INTRODUCTION: There are no reports on vessel reconstruction of right gastro
      omental artery deficits due to pancreatic tumor resection. Here, we describe
      successful arterial reconstruction using the middle colic artery in a patient who
      had undergone esophageal reconstruction with a gastric tube and whose right
      gastro-omental artery had been resected. PRESENTATION OF CASE: A 70-year-old man
      underwent subtotal esophagectomy and reconstructive surgery with a retrosternal
      gastric tube for esophageal cancer. A follow-up computed tomography (CT) scan
      revealed a tumor on the pancreatic head that was adjacent to the right gastro
      omental artery. Pancreaticoduodenectomy (PD) was subsequently performed. The
      gastro-omental artery was resected along with the tumor, creating a 7-cm deficit.
      The anastomosis was performed between the right branch of the middle colic artery
      and the distal end of the right gastro-omental artery. No complications that
      involved blood flow to the reconstructed esophagus were postoperatively observed.
      Four months after surgery, the blood flow to the gastric tube was confirmed by a
      contrast CT scan. DISCUSSION: We reconstructed the right gastro-omental artery
      using the middle colic artery, and not a vein graft, as that would have required
      vessel anastomosis at two locations. The middle colic artery branches on the
      posterior surface of the pancreas, which is located close to the right gastro
      omental artery. CONCLUSION: The middle colic artery provides sufficient blood
      supply to the pulled-up gastric tube. PD can be performed even in patients who
      have undergone esophageal reconstruction.

PMID- 26313337
TI  - First Principles Calculations of Aqueous pKa Values for Organic and Inorganic
      Acids Using COSMO-RS Reveal an Inconsistency in the Slope of the pKa Scale.
AB  - The COSMO-RS method, a combination of the quantum chemical dielectric continuum
      solvation model COSMO with a statistical thermodynamics treatment for more
      realistic solvation (RS) simulations, has been used for the direct prediction of
      pKa constants of a large variety of 64 organic and inorganic acids. A highly
      significant correlation of r(2) = 0.984 with a standard deviation of only 0.49
      between the calculated values of the free energies of dissociation and the
      experimental pKa values was found, without any special adjustment of the method.
      Thus, we have a theoretical a priori prediction method for pKa, which has the
      regression constant and the slope as only adjusted parameters. Such a method can
      be of great value in many areas of physical chemistry, especially in
      pharmaceutical and agrochemical industry. To our surprise, the slope of pKa vs
      DeltaGdiss is only 58% of the theoretically expected value of 1/RTln(10). A
      careful analysis with respect to different contributions as well as a comparison
      with the work of other authors excludes the possibility that the discrepancy is
      due to weaknesses of the calculation method. Hence, we must conclude that the
      experimental pKa scale depends differently on the free energy of dissociation
      than generally assumed. 

PMID- 26313338
TI  - Partial Dislocations in Graphene and Their Atomic Level Migration Dynamics.
AB  - We demonstrate the formation of partial dislocations in graphene at elevated
      temperatures of >=500  degrees C with single atom resolution aberration corrected
      transmission electron microscopy. The partial dislocations spatially redistribute
      strain in the lattice, providing an energetically more favorable configuration to
      the perfect dislocation. Low-energy migration paths mediated by partial
      dislocation formation have been observed, providing insights into the atomistic
      dynamics of graphene during annealing. These results are important for
      understanding the high temperature plasticity of graphene and partial dislocation
      behavior in related crystal systems, such as diamond cubic materials. 

PMID- 26313339
TI  - Evidence for Hydroxamate Siderophores and Other N-Containing Organic Compounds
      Controlling (239,240)Pu Immobilization and Remobilization in a Wetland Sediment.
AB  - Pu concentrations in wetland surface sediments collected downstream of a former
      nuclear processing facility in F-Area of the Savannah River Site (SRS), USA, were
      ~2.5 times greater than those measured in the associated upland aquifer
      sediments; similarly, the Pu concentration solid/water ratios were orders of
      magnitude greater in the wetland than in the low-organic matter content aquifer
      soils. Sediment Pu concentrations were correlated to total organic carbon and
      total nitrogen contents and even more strongly to hydroxamate siderophore (HS)
      concentrations. The HS were detected in the particulate or colloidal phases of
      the sediments but not in the low molecular weight fractions (<1000 Da).
      Macromolecules which scavenged the majority of the potentially mobile Pu were
      further separated from the bulk mobile organic matter fraction ("water extract")
      via an isoelectric focusing experiment (IEF). An electrospray ionization Fourier
      transform ion cyclotron resonance ultrahigh resolution mass spectrometry (ESI
      FTICR-MS) spectral comparison of the IEF extract and a siderophore standard
      (desferrioxamine; DFO) suggested the presence of HS functionalities in the IEF
      extract. This study suggests that while HS are a very minor component in the
      sediment particulate/colloidal fractions, their concentrations greatly exceed
      those of ambient Pu, and HS may play an especially important role in Pu
      immobilization/remobilization in wetland sediments.

PMID- 26313340
TI  - Pan Assay Interference Compounds (PAINS) and Other Promiscuous Compounds in
      Antifungal Research.
AB  - Every week, articles disclosing new antifungal leads reported as promising
      starting points for optimization projects are published. In many cases, the
      mechanism that accounts for their antifungal activity has not been fully
      elucidated. More significantly, the detrimental impact that could result from
      certain embedded chemical features has been underestimated or even overlooked. In
      the course of our research in the agrochemical area, we have concluded that in
      many cases such leads are actually nonoptimizable because they either contain
      what are now recognized as pan assay interference compounds (PAINS) or other
      promiscuous groups. This article is aimed at highlighting the pitfalls we have
      encountered and hopefully to steer other research groups away from them.

PMID- 26313341
TI  - Characterization of a Self-Assembled Monolayer of 1-Thio-beta-D-Glucose with
      Electrochemical Surface Enhanced Raman Spectroscopy Using a Nanoparticle Modified
      Gold Electrode.
AB  - Preparation of a nanoparticle modified gold substrate designed for
      characterization of hydrophilic self-assembled monolayers (SAMs) of 1-thio-beta-D
      glucose (TG) with electrochemical surface-enhanced Raman spectroscopy (EC-SERS)
      is presented. Citrate stabilized gold nanoparticles were deposited on a
      polycrystalline gold electrode and subjected to an electrochemical desorption
      procedure to completely remove all traces of adsorbed citrate. Complete
      desorption of citrate was confirmed by recording cyclic voltammetry curves and
      SERS spectra. The citrate-free nanoparticle modified gold electrode was then
      incubated in a 1 mg mL(-1) aqueous solution of TG for 16 h prior to being
      characterized by EC-SERS. The SERS spectra confirmed that at potentials more
      negative than -0.10 V vs SCE thioglucose forms a monolayer in which the majority
      of the molecules preserve their lactol ring structure and only a small fraction
      of molecules appear to be oxidized. At potentials more positive than -0.10 V, the
      oxidation of TG molecules becomes prominent, and at potentials more positive than
      0.20 V vs SCE, the monolayer of TG consists chiefly of oxidized product. The SERS
      spectra collected in the double layer region suggest the SAM of TG is well
      hydrated and hence can be used for hydrophilic modifications of a gold surface.

PMID- 26313342
TI  - A practical, automated synthesis of meta-[(18)F]fluorobenzylguanidine for
      clinical use.
AB  - Many neuroendocrine tumors, such as neuroblastoma (NB), arise from neural crest
      cells of the sympathetic nervous system. This nerve-like phenotype has been
      exploited for functional imaging using radioactive probes originally designed for
      neuronal and adrenal medullary applications. NB imaging with meta
      [(123)I]iodobenzylguanidine ([(123)I]MIBG) is limited by the emissions of (123)I,
      which lead to poor image resolution and challenges in quantification of its
      accumulation in tumors. meta-[(18)F]Fluorobenzylguanidine ([(18)F]MFBG) is a
      promising alternative to [(123)I]MIBG that could change the standard of practice
      for imaging neuroendocrine tumors, but interest in this PET radiotracer has
      suffered due to its complex and inefficient radiosynthesis. Here we report a two
      step, automated method for the routine production of [(18)F]MFBG by thermolysis
      of a diaryliodonium fluoride and subsequent acid deprotection. The synthesis was
      adapted for use on a commercially available synthesizer for routine production.
      Full characterization of [(18)F]MFBG produced by this route demonstrated the
      tracer's suitability for human use. [(18)F]MFBG was prepared in almost 3-fold
      higher yield than previously reported (31% corrected to end of bombardment, n =
      9) in a synthesis time of 56 min with >99.9% radiochemical purity. Other than pH
      adjustment and dilution of the final product, no reformulation was necessary
      after purification. This method permits the automated production of multidose
      batches of clinical grade [(18)F]MFBG. Moreover, if ongoing clinical imaging
      trials of [(18)F]MFBG are successful, this methodology is suitable for rapid
      commercialization and can be easily adapted for use on most commercial automated
      radiosynthesis equipment. 

PMID- 26313343
TI  - Guanine oxidation product 5-carboxamido-5-formamido-2-iminohydantoin induces
      mutations when bypassed by DNA polymerases and is a substrate for base excision
      repair.
AB  - Guanine (G) is a target for oxidation by reactive oxygen species in DNA, RNA, and
      the nucleotide pool. Damage to DNA yields products with alternative properties
      toward DNA processing enzymes compared to those of the parent nucleotide. A new
      lesion, 5-carboxamido-5-formamido-2-iminohydantoin (2Ih), bearing a stereocenter
      in the base was recently identified from the oxidation of G. DNA polymerase and
      base excision repair processing of this new lesion has now been evaluated. Single
      nucleotide insertion opposite (S)-2Ih and (R)-2Ih in the template strand
      catalyzed by the DNA polymerases Klenow fragment exo(-), DPO4, and Hemo KlenTaq
      demonstrates these lesions to cause point mutations. Specifically, they promote 3
      fold more G.C -> C.G transversion mutations than G.C -> T.A, and (S)-2Ih was 2
      fold more blocking for polymerase bypass than (R)-2Ih. Both diastereomer lesions
      were found to be substrates for the DNA glycosylases NEIL1 and Fpg, and poorly
      excised by endonuclease III (Nth). The activity was independent of the base pair
      partner. Thermal melting, CD spectroscopy, and density functional theory
      geometric optimization calculations were conducted to provide insight into these
      polymerase and DNA glycosylase studies. These results identify that formation of
      the 2Ih lesions in a cell would be mutagenic in the event that they were not
      properly repaired. 

PMID- 26313344
TI  - A challenge for theranostics: is the optimal particle for therapy also optimal
      for diagnostics?
AB  - Theranostics is defined as the combination of therapeutic and diagnostic
      capabilities in the same agent. Nanotechnology is emerging as an efficient
      platform for theranostics, since nanoparticle-based contrast agents are powerful
      tools for enhancing in vivo imaging, while therapeutic nanoparticles may overcome
      several limitations of conventional drug delivery systems. Theranostic
      nanoparticles have drawn particular interest in cancer treatment, as they offer
      significant advantages over both common imaging contrast agents and
      chemotherapeutic drugs. However, the development of platforms for theranostic
      applications raises critical questions; is the optimal particle for therapy also
      the optimal particle for diagnostics? Are the specific characteristics needed to
      optimize diagnostic imaging parallel to those required for treatment
      applications? This issue is examined in the present study, by investigating the
      effect of the gold nanoparticle (GNP) size on tumor uptake and tumor imaging. A
      series of anti-epidermal growth factor receptor conjugated GNPs of different
      sizes (diameter range: 20-120 nm) was synthesized, and then their uptake by human
      squamous cell carcinoma head and neck cancer cells, in vitro and in vivo, as well
      as their tumor visualization capabilities were evaluated using CT. The results
      showed that the size of the nanoparticle plays an instrumental role in
      determining its potential activity in vivo. Interestingly, we found that although
      the highest tumor uptake was obtained with 20 nm C225-GNPs, the highest contrast
      enhancement in the tumor was obtained with 50 nm C225-GNPs, thus leading to the
      conclusion that the optimal particle size for drug delivery is not necessarily
      optimal for imaging. These findings stress the importance of the investigation
      and design of optimal nanoparticles for theranostic applications. 

PMID- 26313345
TI  - Oral health management of 97 patients living with HIV/AIDS in Ribeirao Preto, Sao
      Paulo, Brazil.
AB  - Considering the changes antiretroviral therapy (ART) has brought to the treatment
      of HIV infection, the current clinical and laboratory profiles of HIV/AIDS
      individuals referred to oral health centers are crucially important in
      instructing dentists about the oral health management of these patients. The aim
      of the present study was to determine the clinical and laboratory profiles of HIV
      infected individuals referred to a clinic for patients with special needs between
      2005 and 2012 by retrospectively analyzing their dental records. A total of 97
      records of HIV patients referred to the School of Dentistry of Ribeirao Preto,
      Universidade de Sao Paulo - USP, were analyzed. The Mann-Whitney test was used to
      determine the associations between mean CD4+ counts, mean viral load, and the
      presence of HIV-related oral lesions (HIV-OL). Most of the patients were male,
      and their mean age was 38.3 years. Eighty-nine (92%) patients were on regular
      ART, 77 (79.4%) had a CD4+ count higher than 200 cells/mm3, and 63 (64.9%) had an
      undetectable viral load. Twenty patients (20.6%) presented with some HIV-OL,
      including pseudomembranous and/or erythematous candidiasis and angular cheilitis,
      which were correlated with a low CD4+ count and with an undetectable viral load
      (p < 0.05). Among the branches of dentistry, periodontics, followed by surgery
      and restorative dentistry, was the most sought-after specialty, and no
      intercurrent events were observed during the dental treatment. It may be
      concluded that there are no restrictions on the dental treatment of patients on
      regular ART, It is important, though, that the treatment be based on local
      characteristics and on the prevention of oral diseases. 

PMID- 26313346
TI  - Antimicrobial action of sodium hypochlorite and castor oil solutions for denture
      cleaning - in vitro evaluation.
AB  - The objective of this in vitro study was to evaluate the antimicrobial action of
      sodium hypochlorite (0.25% and 0.50%) and 10% castor oil solutions against
      specific microorganisms, by counting Colony Forming Units (CFU) of clinically
      important bacteria and Candida species. Acrylic resin specimens (n = 320;
      Lucitone 550) were obtained from square metal matrices (10 x 10 x 2 mm),
      sterilized by microwave (650W, for 6 minutes) and contaminated by Staphylococcus
      aureus, Pseudomonas aeruginosa, Candida albicans, Bacillus subtilis, Escherichia
      coli, Streptococcus mutans, Enterococcus faecalis and Candida glabrata. The
      specimens were immersed for 20 minutes in one of the following hygiene solutions
      (n = 10/each): A - 0.25% Sodium hypochlorite; B - 0.5% Sodium hypochlorite; C -
      10% Castor oil solution; and D (Control) - saline. Adhered cells were suspended
      and inoculated into a selective solid medium (37oC for 24 h). The Student's t
      test (alpha = 0.05) was performed to compare log10(CFU+1)/mL between Groups C and
      D. The results showed that sodium hypochlorite (0.25% and 0.5%) completely
      eliminated all detectable microorganisms. The castor oil solution eliminated B.
      subtilis and reduced counts for other strains. Differences between C and D were
      significant (p < 0.05) for all species except for E. faecalis. Both sodium
      hypochlorite solutions (0.25% and 0.5%) were effective in eliminating all
      microorganisms evaluated, and may be useful as cleaning solutions for complete
      dentures. The castor oil solution provided moderate efficacy and performed
      differently on the tested species, with the strongest effect on B. subtilis and
      with non-significant action on E. faecalis. 

PMID- 26313347
TI  - Epidemiological study of traumatic dental injuries in 5- to 6-year-old Brazilian
      children.
AB  - Monitoring traumatic dental injury (TDI) in primary teeth through epidemiological
      cross-sectional surveys provides descriptive information relevant to the
      development of public policies focused on the prevention of such injuries for the
      target population. The aim of this study was to assess the prevalence of TDI in 5
      to 6-year-old Brazilian children and its association with biological and
      socioeconomic factors. A total of 684 children aged 5 to 6 years old, from 11
      public schools in the city of Barueri (Brazil) were evaluated. Clinical
      examinations were carried out in the schools, by two trained and calibrated
      examiners. Gauze and a mouth mirror were used for the examinations. The reported
      TDIs were classified according to the Andreasen (2007) criteria for primary
      teeth. The results showed that 52.3% of the children had TDI. Enamel fracture
      (63.4%) was the most frequently observed sign of TDI, and the most affected teeth
      were the primary maxillary central incisors (26.9% maxillary right central
      incisor and 24% maxillary left central incisor). There was no association between
      the presence of TDI and biological or socioeconomic factors. In conclusion, the
      prevalence of TDI was high and had no statistically significant association with
      biological and socioeconomic factors. 

PMID- 26313348
TI  - Effectiveness of nano-calcium phosphate paste on sensitivity during and after
      bleaching: a randomized clinical trial.
AB  - The study aimed to evaluate the effectiveness of in-office bleaching and
      associated tooth sensitivity on application of nano-calcium phosphate paste as
      desensitizing agent. Bleaching was performed with 35% hydrogen peroxide gel in 40
      patients who were randomly divided into placebo and nano-calcium phosphate paste
      groups. Bleaching efficacy (BE) was evaluated using a value-oriented Vita shade
      guide. Tooth sensitivity was recorded using a numeric rating scale (0-4) during
      bleaching and up to 48 h after each session. The primary outcome of absolute risk
      of tooth sensitivity was compared using the Fisher's exact test (alpha = 0.05).
      The intensity of tooth sensitivity and the efficacy of in-office bleaching were
      also statistically evaluated. No significant differences in absolute risk and
      intensity of tooth sensitivity were detected between the groups (p = 1.0 and p =
      0.53, respectively). BE was also found to be similar between the groups (p =
      0.67). Although the use of a nano-calcium phosphate paste associated with
      fluoride and potassium nitrate did not influence the whitening outcome, but it
      also did not reduce bleaching-induced tooth sensitivity. 

PMID- 26313349
TI  - Applying liquid chromatography-tandem mass spectrometry to assess endodontic
      sealer microleakage.
AB  - The objective of this study was to describe a new method for the quantitative
      analysis of a microleakage of endodontic filling materials. Forty extracted
      single-rooted teeth were randomly divided into three experimental groups. After
      root canal shaping, the experimental groups were filled using the lateral
      condensation technique with the Epiphany system (G1), with gutta-percha +
      Sealapex (G2), and with gutta-percha + AH Plus (G3). Each root was mounted on a
      modified leakage testing device, and caffeine solution was used as a tracer (2000
      ng mL-1, pH 6.0), applied in the coronal direction towards the tooth apex,
      creating a hydrostatic pressure of 2.55 kPa. Presence of caffeine in the
      receiving solution was measured after 10, 30, and 60 days, using high performance
      liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). None of the groups
      presented microleakage at 10 days. At 30 days, G2 and G3 showed similar
      infiltration patterns (means: 16.0 and 13.9 ng mL-1, respectively), whereas G1
      showed significantly higher values (mean: 105.2 ng mL-1). At 60 days, leakage
      values were 182.6 ng mL-1 for G1, 139.0 ng mL-1 for G2, and 53.5 ng mL-1 for G3.
      AH Plus showed the best sealing ability and HPLC-MS/MS showed high sensitivity
      and specificity for tracer quantification.

PMID- 26313350
TI  - Anti-dentine Salivary SIgA in young adults with a history of dental trauma in
      deciduous teeth.
AB  - Anti-dentin autoantibodies are associated with inflammatory root resorption in
      permanent teeth and are modulated by dental trauma and orthodontic force.
      However, it is not known whether deciduous tooth trauma can stimulate the
      development of a humoral immune response against dentin. The aim of this study
      was to evaluate the levels of salivary SIgA reactivity against human dentin
      extract in young adults with a history of trauma in the primary dentition. A
      sample of 78 patients, aged 18 to 25, who had completed an early childhood (0 to
      5 years old) caries prevention program years earlier at the Universidade Estadual
      de Londrina Pediatric Clinic, underwent radiographic examination and salivary
      sampling. Anti-dentin SIgA levels were analyzed by immunoenzymatic assay and
      Western blotting. Although dental trauma to deciduous teeth had occurred in 34
      (43.6%) of the patients, no differences in SIgA levels were detected between
      individuals who had experienced trauma and those who had not (p > 0.05).
      Multivariate regression analysis showed no association between dental trauma and
      SIgA levels (p > 0.05). Patients with a history of deciduous trauma presented low
      levels of anti-dentin antibodies, associated with orthodontic root resorption (p
      < 0.05). Western blot analysis showed that salivary antibodies recognized a
      single band of approximately 45 kDa in dentin extract. We concluded that salivary
      SIgA recognizes a specific component of the dentin matrix and that anti-dentin
      antibodies were not triggered by trauma to primary teeth. However, trauma to
      deciduous teeth may down-modulate SIgA in response to orthodontic root response. 

PMID- 26313351
TI  - The impact of social determinants on schoolchildren's oral health in Brazil.
AB  - The aim of this study was to evaluate the impact of socioeconomic status, home
      environment, and self-perception of health conditions on schoolchildren's dental
      caries experience. A total of 515 twelve-year-old schoolchildren from Juiz de
      Fora, State of Minas Gerais, Brazil, were selected into a random multistage
      sample. The schoolchildren were examined for the presence of caries lesions using
      the decayed/missing/filled teeth (DMFT) index and categorized as caries-free
      (DMFT = 0) or with caries experience (DMFT > 0). The participants and their
      parents were asked to answer a questionnaire about socioeconomic status, home
      environment, and self-perception of their health conditions. The hierarchical
      multiple regression model was used to assess the associations, since a binary
      response variable was assumed. The bivariate analysis revealed that variables at
      four levels, such as type of school, monthly family income, parents' education,
      home ownership, number of people living in the household, household overcrowding,
      parents' perception of their children's oral health, and schoolchildren's self
      perception of their oral health (p < 0.05), were significantly associated with
      children's worse dental caries conditions. The regression model results showed
      that type of school and monthly family income had a strong negative effect on
      schoolchildren's dental caries experience (p < 0.05) in the final statistical
      model, where all levels were included. It was observed that socioeconomic factors
      were considered a strong risk indicator of schoolchildren's caries experience
      among the investigated social determinants of oral health. 

PMID- 26313352
TI  - Synthesis and characterisation of thioether functionalised gallium and indium
      alkoxides.
AB  - This paper provides evidence of formerly unknown thioether coordination in metal
      alkoxides. The thioether functionalised alkanols serving as alcoholate ligands
      have been prepared by a generic route. The gallium and indium alkoxides provide
      the first evidence for sulphur coordination in the liquid and solid state in
      metal alkoxide derivatives. The presence of amines suppresses the coordination of
      thioether moieties leading to a well-known bonding mode in aminoalcoholates. 

PMID- 26313353
TI  - Anisotropic molecular hopping at the solid-nematic interface.
AB  - Single molecule tracking was used to observe intermittent and anisotropic
      molecular motion at the solid-nematic interface. Although the interfacial
      diffusion was dramatically slower than self-diffusion in the nematic, the
      diffusion anisotropy was the same at the interface and in bulk, supporting the
      desorption-mediated mechanism of interfacial diffusion, where molecules sample
      the physical properties of the vicinal fluid phase during flights, and the
      magnitude of the interfacial diffusion coefficient is primarily determined by the
      distribution of waiting times between flights. 

PMID- 26313354
TI  - Effective strategies for weight loss in post-partum women: a systematic review
      and meta-analysis.
AB  - Post-partum weight loss is critical to preventing and managing obesity in women,
      but the results from lifestyle interventions are variable and the components
      associated with successful outcomes are not yet clearly identified. This study
      aimed to identify lifestyle intervention strategies associated with weight loss
      in post-partum women. MEDLINE, EMBASE, PubMed, CINAHL and four other databases
      were searched for lifestyle intervention studies (diet or exercise or both) in
      post-partum women (within 12 months of delivery) published up to July 2014. The
      primary outcome was weight loss. Subgroup analyses were conducted for self
      monitoring, individual or group setting, intervention duration, intervention
      types, the use of technology as a support, and home- or centre-based
      interventions. From 12,673 studies, 46 studies were included in systematic review
      and 32 randomized controlled trials were eligible for meta-analysis (1,892 women,
      age 24-36 years). Studies with self-monitoring had significantly greater weight
      lost than those without (-4.61 kg [-7.08, -2.15] vs. -1.34 kg [-1.66, -1.02], P =
      0.01 for subgroup differences). Diet and physical activity when combined were
      significantly more effective on weight loss compared with physical activity alone
      (-3.24 kg [-4.59, -1.90] vs. -1.63 kg [-2.16, -1.10], P < 0.001 for subgroup
      differences). Lifestyle interventions that use self-monitoring and take a
      combined diet-and-exercise approach have significantly greater weight loss in
      post-partum women. 

PMID- 26313355
TI  - CETP Expression Protects Female Mice from Obesity-Induced Decline in Exercise
      Capacity.
AB  - Pharmacological approaches to reduce obesity have not resulted in dramatic
      reductions in the risk of coronary heart disease (CHD). Exercise, in contrast,
      reduces CHD risk even in the setting of obesity. Cholesteryl Ester Transfer
      Protein (CETP) is a lipid transfer protein that shuttles lipids between serum
      lipoproteins and tissues. There are sexual-dimorphisms in the effects of CETP in
      humans. Mice naturally lack CETP, but we previously reported that transgenic
      expression of CETP increases muscle glycolysis in fasting and protects against
      insulin resistance with high-fat diet (HFD) feeding in female but not male mice.
      Since glycolysis provides an important energy source for working muscle, we aimed
      to define if CETP expression protects against the decline in exercise capacity
      associated with obesity. We measured exercise capacity in female mice that were
      fed a chow diet and then switched to a HFD. There was no difference in exercise
      capacity between lean, chow-fed CETP female mice and their non-transgenic
      littermates. Female CETP transgenic mice were relatively protected against the
      decline in exercise capacity caused by obesity compared to WT. Despite gaining
      similar fat mass after 6 weeks of HFD-feeding, female CETP mice showed a nearly
      two-fold increase in run distance compared to WT. After an additional 6 weeks of
      HFD-feeding, mice were subjected to a final exercise bout and muscle mitochondria
      were isolated. We found that improved exercise capacity in CETP mice corresponded
      with increased muscle mitochondrial oxidative capacity, and increased expression
      of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC
      1alpha). These results suggest that CETP can protect against the obesity-induced
      impairment in exercise capacity and may be a target to improve exercise capacity
      in the context of obesity. 

PMID- 26313356
TI  - Social Costs of Iron Deficiency Anemia in 6-59-Month-Old Children in India.
AB  - INTRODUCTION: Inadequate nutrition has a severe impact on health in India.
      According to the WHO, iron deficiency is the single most important nutritional
      risk factor in India, accounting for more than 3% of all disability-adjusted life
      years (DALYs) lost. We estimate the social costs of iron deficiency anemia (IDA)
      in 6-59-month-old children in India in terms of intangible costs and production
      losses. MATERIALS AND METHODS: We build a health economic model estimating the
      life-time costs of a birth cohort suffering from IDA between the ages of 6 and 59
      months. The model is stratified by 2 age groups (6-23 and 24-59-months), 2
      geographical areas (urban and rural), 10 socio-economic strata and 3 degrees of
      severity of IDA (mild, moderate and severe). Prevalence of anemia is calculated
      with the last available National Family Health Survey. Information on the health
      consequences of IDA is extracted from the literature. RESULTS: IDA prevalence is
      49.5% in 6-23-month-old and 39.9% in 24-58-month-old children. Children living in
      poor households in rural areas are particularly affected but prevalence is high
      even in wealthy urban households. The estimated yearly costs of IDA in 6-59-month
      old children amount to intangible costs of 8.3 m DALYs and production losses of
      24,001 m USD, equal to 1.3% of gross domestic product. Previous calculations have
      considerably underestimated the intangible costs of IDA as the improved WHO
      methodology leads to a threefold increase of DALYs due to IDA. CONCLUSION:
      Despite years of iron supplementation programs and substantial economic growth,
      IDA remains a crucial public health issue in India and an obstacle to the
      economic advancement of the poor. Young children are especially vulnerable due to
      the irreversible effects of IDA on cognitive development. Our research may
      contribute to the design of new effective interventions aiming to reduce IDA in
      early childhood.

PMID- 26313357
TI  - Chemical Signals and Mechanosensing in Bacterial Responses to Their Environment.

PMID- 26313359
TI  - Structural Morphology of Molars in Large Mammalian Herbivores: Enamel Content
      Varies between Tooth Positions.
AB  - The distribution of dental tissues in mammalian herbivores can be very different
      from taxon to taxon. While grazers tend to have more elaborated and complexly
      folded enamel ridges, browsers have less complex enamel ridges which can even be
      so far reduced that they are completely lost. The gradient in relative enamel
      content and complexity of structures has so far not been addressed within a
      single species. However, several studies have noted tooth position specific wear
      rates in small mammals (rabbits, guinea pigs) which may be related to individual
      tooth morphology. We investigate whether differentiated enamel content by tooth
      position is also to be found in large herbivores. We use CT-scanning techniques
      to quantify relative enamel content in upper and lower molar teeth of 21 large
      herbivorous mammal species. By using a broad approach and including both
      perissodactyls and artiodactyls, we address phylogenetic intraspecific
      differences in relative enamel content. We find that enamel is highly unevenly
      distributed among molars (upper M1, M2, M3 and lower m1, m2, m3) in most taxa and
      that relative enamel content is independent of phylogeny. Overall, relative
      enamel content increases along the molar tooth row and is significantly higher in
      lower molars compared to upper molars. We relate this differential enamel content
      to prolonged mineralisation in the posterior tooth positions and suggest a
      compensatory function of m3 and M3 for functional losses of anterior teeth. 

PMID- 26313358
TI  - Increase in Dickkopf-1 Serum Level in Recent Spondyloarthritis. Data from the
      DESIR Cohort.
AB  - OBJECTIVES: To investigate DKK-1 and SOST serum levels among patients with recent
      inflammatory back pain (IBP) fulfilling ASAS criteria for SpA and associated
      factors. METHODS: The DESIR cohort is a prospective, multicenter French cohort of
      708 patients with early IBP (duration >3 months and <3 years) suggestive of
      AxSpA. DKK-1 and SOST serum levels were assessed at baseline and were compared
      between the subgroup of patients fulfilling ASAS criteria for SpA (n = 486;
      68.6%) and 80 healthy controls. RESULTS: Mean SOST serum levels were lower in
      ASAS+ patients than healthy controls (49.21 +/- 25.9 vs. 87.8 +/- 26 pmol/L;
      p<0.0001). In multivariate analysis, age (p = 5.4 10-9), CRP level (p<0.0001) and
      serum DKK-1 level (p = 0.001) were associated with SOST level. Mean DKK-1 serum
      levels were higher in axial SpA patients than controls (30.03 +/- 15.5 vs. 11.6
      +/- 4.2 pmol/L; p<0.0001). In multivariate analysis, DKK-1 serum levels were
      associated with male gender (p = 0.03), CRP level (p = 0.006), SOST serum level
      (p = 0.002) and presence of sacroiliitis on radiography (p = 0.05). Genetic
      association testing of 10 SNPs encompassing the DKK-1 locus failed to demonstrate
      a significant contribution of genetics to control of DKK-1 serum levels.
      CONCLUSIONS: DKK-1 serum levels were increased and SOST levels were decreased
      among a large cohort of patients with early axial SpA compared to healthy
      controls. DKK-1 serum levels were mostly associated with biological inflammation
      and SOST serum levels.

PMID- 26313360
TI  - Chitosan nanoparticle-mediated delivery of miRNA-34a decreases prostate tumor
      growth in the bone and its expression induces non-canonical autophagy.
AB  - While several new therapies are FDA-approved for bone-metastatic prostate cancer
      (PCa), patient survival has only improved marginally. Here, we report that
      chitosan nanoparticle-mediated delivery of miR-34a, a tumor suppressive microRNA
      that downregulates multiple gene products involved in PCa progression and
      metastasis, inhibited prostate tumor growth and preserved bone integrity in a
      xenograft model representative of established PCa bone metastasis. Expression of
      miR-34a induced apoptosis in PCa cells, and, in accord with downregulation of
      targets associated with PCa growth, including MET and Axl and c-Myc, also induced
      a form of non-canonical autophagy that is independent of Beclin-1, ATG4, ATG5 and
      ATG7. MiR-34a-induced autophagy is anti-proliferative in prostate cancer cells,
      as blocking apoptosis still resulted in growth inhibition of tumor cells. Thus,
      combined effects of autophagy and apoptosis are responsible for miR-34a-mediated
      prostate tumor growth inhibition, and have translational impact, as this non
      canonical form of autophagy is tumor inhibitory. Together, these results provide
      a new understanding of the biological effects of miR-34a and highlight the
      clinical potential for miR-34a delivery as a treatment for bone metastatic
      prostate cancer. 

PMID- 26313361
TI  - Impact of Genomics Platform and Statistical Filtering on Transcriptional
      Benchmark Doses (BMD) and Multiple Approaches for Selection of Chemical Point of
      Departure (PoD).
AB  - Many regulatory agencies are exploring ways to integrate toxicogenomic data into
      their chemical risk assessments. The major challenge lies in determining how to
      distill the complex data produced by high-content, multi-dose gene expression
      studies into quantitative information. It has been proposed that benchmark dose
      (BMD) values derived from toxicogenomics data be used as point of departure (PoD)
      values in chemical risk assessments. However, there is limited information
      regarding which genomics platforms are most suitable and how to select
      appropriate PoD values. In this study, we compared BMD values modeled from RNA
      sequencing-, microarray-, and qPCR-derived gene expression data from a single
      study, and explored multiple approaches for selecting a single PoD from these
      data. The strategies evaluated include several that do not require prior
      mechanistic knowledge of the compound for selection of the PoD, thus providing
      approaches for assessing data-poor chemicals. We used RNA extracted from the
      livers of female mice exposed to non-carcinogenic (0, 2 mg/kg/day, mkd) and
      carcinogenic (4, 8 mkd) doses of furan for 21 days. We show that transcriptional
      BMD values were consistent across technologies and highly predictive of the two
      year cancer bioassay-based PoD. We also demonstrate that filtering data based on
      statistically significant changes in gene expression prior to BMD modeling
      creates more conservative BMD values. Taken together, this case study on mice
      exposed to furan demonstrates that high-content toxicogenomics studies produce
      robust data for BMD modelling that are minimally affected by inter-technology
      variability and highly predictive of cancer-based PoD doses. 

PMID- 26313363
TI  - Addressing potential role of magnesium dyshomeostasis to improve treatment
      efficacy for epilepsy: A reexamination of the literature.
AB  - Magnesium (Mg(2+) ) is an abundant mineral in the body serving many biochemical
      functions. Magnesium supplementation has been shown to raise seizure threshold in
      animal and human studies, but the etiological contribution of magnesium
      deficiency to the onset and maintenance of epilepsy, as well as the degree to
      which it impacts antiepileptic drug efficacy, remains poorly understood. This may
      be due, at least in part, to the inherent limitations of commonly used serum
      levels as a measure of functional magnesium status, as well as insufficient data
      regarding relative bioavailabilities of various magnesium salts and chelates for
      use with humans. To date, 1 randomized clinical trial has been conducted
      assessing Mg(2+) supplementation in epilepsy, and findings yielded promising
      results. Yet a notable dearth in the literature remains, and more studies are
      needed. To better understand the potential role of magnesium deficiency as a
      causal factor in epilepsy, more convenient and accurate measurement methods
      should to be developed and employed in randomized, controlled trials of oral
      magnesium supplementation in epilepsy. Findings from such studies have the
      potential to facilitate far-reaching clinical and economic improvements in
      epilepsy treatment standards. 

PMID- 26313362
TI  - PD-1 and PD-L1 Expression in NSCLC Indicate a Favorable Prognosis in Defined
      Subgroups.
AB  - BACKGROUND: Immunotherapy can become a crucial therapeutic option to improve
      prognosis for lung cancer patients. First clinical trials with therapies
      targeting the programmed cell death receptor PD-1 and its ligand PD-L1 have shown
      promising results in several solid tumors. However, in lung cancer the
      diagnostic, prognostic and predictive value of these immunologic factors remains
      unclear. METHOD: The impact of both factors was evaluated in a study collective
      of 321 clinically well-annotated patients with non-small lung cancer (NSCLC)
      using immunohistochemistry. RESULTS: PD-1 expression by tumor infiltrating
      lymphocytes (TILs) was found in 22%, whereas tumor cell associated PD-L1
      expression was observed in 24% of the NSCLC tumors. In Fisher's exact test a
      positive correlation was found for PD-L1 and Bcl-xl protein expression (p =
      0.013). Interestingly, PD-L1 expression on tumor cells was associated with
      improved overall survival in pulmonary squamous cell carcinomas (SCC, p = 0.042,
      log rank test), with adjuvant therapy (p = 0.017), with increased tumor size (pT2
      4, p = 0.039) and with positive lymph node status (pN1-3, p = 0.010). These
      observations were confirmed by multivariate cox regression models. CONCLUSION:
      One major finding of our study is the identification of a prognostic implication
      of PD-L1 in subsets of NSCLC patients with pulmonary SCC, with increased tumor
      size, with a positive lymph node status and NSCLC patients who received adjuvant
      therapies. This study provides first data for immune-context related risk
      stratification of NSCLC patients. Further studies are necessary both to confirm
      this observation and to evaluate the predictive value of PD-1 and PD-L1 in NSCLC
      in the context of PD-1 inhibition.

PMID- 26313364
TI  - Planar, Fluorescent Push-Pull System That Comprises Benzofuran and Iminocoumarin
      Moieties.
AB  - Previously unknown, vertically linked heterocycles comprised of benzofuran and
      iminocoumarin moieties have been synthesized directly from 1,5
      dibenzoyloxyanthraquinone and arylacetonitriles via double Knoevenagel
      condensation followed by formal HCN elimination. The structural assembly of fully
      conjugated, electron-rich benzofuran and electron-deficient iminocoumarin is
      responsible for the strongly polarized nature of these heterocycles which
      translates into their polarity-sensitive fluorescence. 

PMID- 26313365
TI  - Association of White Blood Cell Count and Differential with the Incidence of
      Atrial Fibrillation: The Atherosclerosis Risk in Communities (ARIC) Study.
AB  - BACKGROUND: Although inflammation is involved in the development of atrial
      fibrillation (AF), the association of white blood cell (WBC) count and
      differential with AF has not been thoroughly examined in large cohorts with
      extended follow-up. METHODS: We studied 14,500 men and women (25% blacks, 55%
      women, mean age 54) free of AF at baseline (1987-89) from the Atherosclerosis
      Risk in Communities (ARIC) study, a community-based cohort in the United States.
      Incident AF cases through 2010 were identified from study electrocardiograms,
      hospital discharge records and death certificates. Multivariable Cox proportional
      hazards regression was used to estimate hazard ratios (HR) and 95% confidence
      intervals (CI) for AF associated with WBC count and differential. RESULTS: Over a
      median follow-up time of 21.5 years for the entire cohort, 1928 participants had
      incident AF. Higher total WBC count was associated with higher AF risk
      independent of AF risk factors and potential confounders (HR 1.09, 95% CI 1.04
      1.15 per 1-standard deviation [SD] increase). Higher neutrophil and monocyte
      counts were positively associated with AF risk, while an inverse association was
      identified between lymphocyte count and AF (multivariable adjusted HRs 1.16, 95%
      CI 1.09-1.23; 1.05, 95% CI 1.00-1.11; 0.91, 95% CI 0.86-0.97 per 1-SD,
      respectively). No significant association was identified between eosinophils or
      basophils and AF. CONCLUSIONS: High total WBC, neutrophil, and monocyte counts
      were each associated with higher AF risk while lymphocyte count was inversely
      associated with AF risk. Systemic inflammation may underlie this association and
      requires further investigation for strategies to prevent AF.

PMID- 26313366
TI  - Involvement of PSMD10, CDK4, and Tumor Suppressors in Development of Intrahepatic
      Cholangiocarcinoma of Syrian Golden Hamsters Induced by Clonorchis sinensis and N
      Nitrosodimethylamine.
AB  - BACKGROUND: Clonorchis sinensis is a group-I bio-carcinogen for
      cholangiocarcinoma (CCA). Although the epidemiological evidence links
      clonorchiasis and CCA, the underlying molecular mechanism involved in this
      process is poorly understood. In the present study, we investigated expression of
      oncogenes and tumor suppressors, including PSMD10, CDK4, p53 and RB in C.
      sinensis induced hamster CCA model. METHODS: Different
      histochemical/immunohistochemical techniques were performed to detect CCA in 4
      groups of hamsters: uninfected control (Ctrl.), infected with C. sinensis (Cs),
      ingested N-nitrosodimethylamine (NDMA), and both Cs infected and NDMA introduced
      (Cs+NDMA). The liver tissues from all groups were analyzed for gene/protein
      expressions by quantitative PCR (qPCR) and western blotting. PRINCIPAL FINDINGS:
      CCA was observed in all hamsters of Cs+NDMA group with well, moderate, and poorly
      differentiated types measured in 21.8% +/- 1.5%, 13.3% +/- 1.3%, and 10.8% +/-
      1.3% of total tissue section areas respectively. All CCA differentiations
      progressed in a time dependent manner, starting from the 8th week of infection.
      CCA stroma was characterized with increased collagen type I, mucin, and
      proliferative cell nuclear antigen (PCNA). The qPCR analysis showed PSMD10, CDK4
      and p16INK4 were over-expressed, whereas p53 was under-expressed in the Cs+NDMA
      group. We observed no change in RB1 at mRNA level but found significant down
      regulation of RB protein. The apoptosis related genes, BAX and caspase 9 were
      found downregulated in the CCA tissue. Gene/protein expressions were matched well
      with the pathological changes of different groups except the NDMA group. Though
      the hamsters in the NDMA group showed no marked pathological lesions, we observed
      over-expression of Akt/PKB and p53 genes proposing molecular interplay in this
      group which might be related to the CCA initiation in this animal model.
      CONCLUSIONS/SIGNIFICANCE: The present findings suggest that oncogenes, PSMD10 and
      CDK4, and tumor suppressors, p53 and RB, are involved in the carcinogenesis
      process of C. sinensis induced CCA in hamsters.

PMID- 26313367
TI  - Opioid abuse and hospitalization rates in patients with schizophrenia.
AB  - BACKGROUND: Substance abuse worsens the course of schizophrenia, but it is not
      known whether or not there are differences between specific substances concerning
      their association with the hospitalizations of patients with schizophrenia. AIMS:
      The primary aims of this study were to examine the possible associations between
      amphetamine, cannabis, and opioid abuse, and the risk of hospitalizations among
      patients with schizophrenia. METHODS: The study population consisted of 146
      patients with ICD-defined schizophrenia from two different geographical sites in
      Finland, and it included both inpatients and outpatients. Data were collected
      retrospectively from the patients' medical files. Substance abuse was defined as
      either harmful use or dependence according to ICD-10. RESULTS: The cumulative
      prevalence of substance abuse was 10.9% (16/146) for cannabis, 8.9% (13/146) for
      amphetamine, and 4.1% (6/146) for opioids. Among patients with schizophrenia and
      abuse of any substance, the number of hospitalizations was about 1.5-fold when
      compared to those without substance abuse. The incidence rate ratio for
      hospitalizations was 2.9 (95% CI 2.47-3.63) for opioids, 2.0 (1.71-2.41) for
      amphetamine, and 1.6 (1.33-1.84) for cannabis, when compared with no abuse of
      each substance. The risk of hospitalizations was significantly higher for opioids
      when compared with amphetamine (p < 0.001) or cannabis (p < 0.001). CONCLUSIONS:
      Harmful use or dependence of opioids among patients with schizophrenia is
      associated with significantly higher risk of hospitalizations than either harmful
      use or dependence of amphetamine or cannabis.

PMID- 26313369
TI  - Treating your own students: Ethical challenges for mental health professionals.

PMID- 26313368
TI  - Activation of Six1 Expression in Vertebrate Sensory Neurons.
AB  - SIX1 homeodomain protein is one of the essential key regulators of sensory organ
      development. Six1-deficient mice lack the olfactory epithelium, vomeronasal
      organs, cochlea, vestibule and vestibuloacoustic ganglion, and also show poor
      neural differentiation in the distal part of the cranial ganglia. Simultaneous
      loss of both Six1 and Six4 leads to additional abnormalities such as small
      trigeminal ganglion and abnormal dorsal root ganglia (DRG). The aim of this study
      was to understand the molecular mechanism that controls Six1 expression in
      sensory organs, particularly in the trigeminal ganglion and DRG. To this end, we
      focused on the sensory ganglia-specific Six1 enhancer (Six1-8) conserved between
      chick and mouse. In vivo reporter assays using both animals identified an
      important core region comprising binding consensus sequences for several
      transcription factors including nuclear hormone receptors, TCF/LEF, SMAD, POU
      homeodomain and basic-helix-loop-helix proteins. The results provided information
      on upstream factors and signals potentially relevant to Six1 regulation in
      sensory neurons. We also report the establishment of a new transgenic mouse line
      (mSix1-8-NLSCre) that expresses Cre recombinase under the control of mouse Six1
      8. Cre-mediated recombination was detected specifically in ISL1/2-positive
      sensory neurons of Six1-positive cranial sensory ganglia and DRG. The unique
      features of the mSix1-8-NLSCre line are the absence of Cre-mediated recombination
      in SOX10-positive glial cells and central nervous system and ability to induce
      recombination in a subset of neurons derived from the olfactory
      placode/epithelium. This mouse model can be potentially used to advance research
      on sensory development.

PMID- 26313370
TI  - Physical frailty in late-life depression is associated with deficits in speed
      dependent executive functions.
AB  - OBJECTIVE: The aim of this study was to examine the association between physical
      frailty and neurocognitive performance in late-life depression (LLD). METHODS:
      Cross-sectional design using baseline data from a treatment study of late-life
      depression was used in this study. Individuals aged 60 years and older were
      diagnosed with major depressive disorder at time of assessment (N = 173). All
      participants received clinical assessment of depression and completed
      neuropsychological testing during a depressive episode. Physical frailty was
      assessed using an adaptation of the FRAIL scale. Neuropsychological domains were
      derived from a factor analysis that yielded three factors: (i) speeded executive
      and fluency, (ii) episodic memory, and (iii) working memory. Associations were
      examined with bivariate tests and multivariate models. RESULTS: Depressed
      individuals with a FRAIL score >1 had worse performance than nonfrail depressed
      across all three factors; however, speeded executive and fluency was the only
      factor that remained significant after controlling for depression symptom
      severity and demographic characteristics. CONCLUSIONS: Although physical frailty
      is associated with broad neurocognitive deficits in LLD, it is most robustly
      associated with deficits in speeded executive functions and verbal fluency.
      Causal inferences are limited by the cross-sectional design, and future research
      would benefit from a comparison group of nondepressed older adults with similar
      levels of frailty. Research is needed to understand the mechanisms underlying
      associations among depression symptoms, physical frailty, and executive
      dysfunction and how they are related to the cognitive and symptomatic course of
      LLD.

PMID- 26313372
TI  - Association Between Use of the 21-Gene Recurrence Score Assay and Receipt of
      Chemotherapy Among Medicare Beneficiaries With Early-Stage Breast Cancer, 2005
      2009.
AB  - IMPORTANCE: Guidelines recommend consideration of chemotherapy for most patients
      with early-stage, estrogen receptor-positive, invasive breast cancer in the
      absence of additional prognostic information. The 21-gene recurrence score (RS)
      assay has been shown in limited academic settings to reduce physician
      recommendations for adjuvant chemotherapy. Associations between the adoption of
      the assay and receipt of chemotherapy in the general population have not been
      examined. OBJECTIVE: To examine whether adoption of the RS assay in a nationally
      representative sample of patients with early-stage breast cancer was associated
      with use of chemotherapy. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort
      study of Medicare beneficiaries who received a diagnosis of incident breast
      cancer between 2005 and 2009 using Surveillance, Epidemiology, and End Results
      data set with linked Medicare claims. MAIN OUTCOMES AND MEASURES: Receipt of
      chemotherapy within 12 months after diagnosis. RESULTS: A total of 44,044
      patients had low-risk (24.0%), intermediate-risk (51.3%), or high-risk disease
      (24.6%, lymph node positive) as defined by National Comprehensive Cancer Network
      (NCCN) guidelines and met the study criteria. We observed no overall association
      between receipt of the RS assay and chemotherapy (odds ratio [OR], 1.03 [99% CI,
      0.88-1.19]). In multivariable analysis, there was a significant interaction
      between NCCN risk and use of the RS assay, with assay use associated with lower
      chemotherapy use in high-risk patients (OR, 0.36 [99% CI, 0.26-0.50]) and greater
      chemotherapy use in low-risk patients (OR, 3.71 [99% CI, 2.30-5.98]), compared
      with no receipt of the assay (P=.006 for the overall interaction). Results were
      similar in prespecified subgroup analyses of patients 70 years and younger, with
      the exception of a shift toward lower chemotherapy use during 2008 (OR, 0.90 [99%
      CI, 0.77-.1.05]; P=.09) and 2009 (OR, 0.81 [99% CI, 0.66-0.99]; P=.007). In
      unadjusted analyses, overall chemotherapy use decreased over time in patients 70
      years or younger with high-risk disease and those receiving the assay.
      CONCLUSIONS AND RELEVANCE: The impact of the adoption of the RS assay on receipt
      of chemotherapy was strongly population dependent and was associated with
      relatively lower chemotherapy use in groups with high-risk disease and relatively
      higher chemotherapy use in patients with low-risk disease. Overall use of
      chemotherapy decreased during the study period in patients who were most likely
      to receive chemotherapy.

PMID- 26313373
TI  - Quantitative detection of rare interphase chromosome breaks and translocations by
      high-throughput imaging.
AB  - We report a method for the sensitive detection of rare chromosome breaks and
      translocations in interphase cells. HiBA-FISH (High-throughput break-apart FISH)
      combines high-throughput imaging with the measurement of the spatial separation
      of FISH probes flanking target genome regions of interest. As proof-of-principle,
      we apply hiBA-FISH to detect with high sensitivity and specificity rare
      chromosome breaks and translocations in the anaplastic large cell lymphoma
      breakpoint regions of NPM1 and ALK. This method complements existing approaches
      to detect translocations by overcoming the need for precise knowledge of
      translocation breakpoints and it extends traditional FISH by its quantitative
      nature. 

PMID- 26313374
TI  - Nipple-sparing mastectomy in patients with BRCA1/2 mutations and variants of
      uncertain significance.
AB  - BACKGROUND: Nipple-sparing mastectomy (NSM) is associated with improved cosmesis
      and is being performed increasingly. Its role in BRCA mutation carriers has not
      been well described. This was a study of the indications for, and outcomes of,
      NSM in BRCA mutation carriers. METHODS: BRCA mutation carriers who underwent NSM
      were identified. Details of patient demographics, surgical procedures,
      complications, and relevant disease stage and follow-up were recorded. RESULTS: A
      total of 177 NSMs were performed in 89 BRCA mutation carriers between September
      2005 and December 2013. Twenty-six patients of median age 41 years had NSM for
      early-stage breast cancer and a contralateral prophylactic mastectomy. Mean
      tumour size was 1.4 (range 0.1-3.5) cm. Sixty-three patients of median age 39
      years had prophylactic NSM, eight of whom had an incidental diagnosis of ductal
      carcinoma in situ. There were no local or regional recurrences in the 26 patients
      with breast cancer at a median follow-up of 28 (i.q.r. 15-43) months. There were
      no newly diagnosed breast cancers in the 63 patients undergoing prophylactic NSM
      at a median follow-up of 26 (11-42) months. All patients had immediate breast
      reconstruction. Five patients (6 per cent) required subsequent excision of the
      nipple-areola complex for oncological or other reasons. Skin desquamation
      occurred in 68 (38.4 per cent) of the 177 breasts, and most resolved without
      intervention. Debridement was required in 13 (7.3 per cent) of the 177 breasts,
      and tissue-expander or implant removal was necessary in six instances (3.4 per
      cent). CONCLUSION: NSM is an acceptable choice for patients with BRCA mutations,
      with no evidence of compromise to oncological safety at short-term follow-up.
      Complication rates were acceptable, and subsequent excision of the nipple-areola
      complex was rarely required.

PMID- 26313376
TI  - Cirrhosis and dysbiosis: New insights from next-generation sequencing.

PMID- 26313375
TI  - Mechanistic Implications of the Unique Structural Features and Dimerization of
      the Cytoplasmic Domain of the Pseudomonas Sigma Regulator, PupR.
AB  - Gram-negative bacteria tightly regulate intracellular levels of iron, an
      essential nutrient. To ensure this strict control, some outer membrane TonB
      dependent transporters (TBDTs) that are responsible for iron import stimulate
      their own transcription in response to extracellular binding by an iron-laden
      siderophore. This process is mediated by an inner membrane sigma regulator
      protein (an anti-sigma factor) that transduces an unknown periplasmic signal from
      the TBDT to release an intracellular sigma factor from the inner membrane, which
      ultimately upregulates TBDT transcription. Here, we use the Pseudomonas putida
      ferric-pseudobactin BN7/BN8 sigma regulator, PupR, as a model system to
      understand the molecular mechanism of this conserved class of sigma regulators.
      We have determined the X-ray crystal structure of the cytoplasmic anti-sigma
      domain (ASD) of PupR to 2.0 A. Size exclusion chromatography, small-angle X-ray
      scattering, and sedimentation velocity analytical ultracentrifugation all
      indicate that, in contrast to other ASDs, the PupR-ASD exists as a dimer in
      solution. Mutagenesis of residues at the dimer interface identified from the
      crystal structure disrupts dimerization and protein stability, as determined by
      sedimentation velocity analytical ultracentrifugation and thermal denaturation
      circular dichroism spectroscopy. These combined results suggest that this type of
      inner membrane sigma regulator may utilize an unusual mechanism to sequester
      their cognate sigma factors and prevent transcription activation. 

PMID- 26313377
TI  - Pirinixic acids: flexible fatty acid mimetics with various biological activities.
AB  - Pirinixic acid is a typical fatty acid mimetic and was developed as synthetic
      antihyperlipidemic agent. While its target remained unknown in the early
      development, it has later been characterized as dual PPARalpha/gamma agonist.
      Based on this activity, pirinixic acid has served as a lead compound for several
      structure-activity relationship (SAR) studies addressing diverse targets for
      lipid mimetics. Many structural variants of pirinixic acid descendants have been
      developed and thereby potent agents on metabolic, inflammatory and
      neuroprotective targets were discovered of which some have proven in vivo
      efficacy. This article reviews pirinixic acid descendants along with their in
      vitro-pharmacological profiles, summarizes their in vivo data and finally gives a
      future perspective for this valuable class of fatty acid mimetics. 

PMID- 26313378
TI  - Trajectory Control of Self-Propelled Micromotors Using AC Electrokinetics.
AB  - 3D control of the motion of self-powered micromotors is demonstrated using AC
      electrokinetics by applying an AC electric field on indium tin oxide transparent
      electrodes. 

PMID- 26313380
TI  - New perspectives in human tear analysis?

PMID- 26313379
TI  - GARN: Sampling RNA 3D Structure Space with Game Theory and Knowledge-Based
      Scoring Strategies.
AB  - Cellular processes involve large numbers of RNA molecules. The functions of these
      RNA molecules and their binding to molecular machines are highly dependent on
      their 3D structures. One of the key challenges in RNA structure prediction and
      modeling is predicting the spatial arrangement of the various structural elements
      of RNA. As RNA folding is generally hierarchical, methods involving coarse
      grained models hold great promise for this purpose. We present here a novel
      coarse-grained method for sampling, based on game theory and knowledge-based
      potentials. This strategy, GARN (Game Algorithm for RNa sampling), is often much
      faster than previously described techniques and generates large sets of solutions
      closely resembling the native structure. GARN is thus a suitable starting point
      for the molecular modeling of large RNAs, particularly those with experimental
      constraints. GARN is available from: http://garn.lri.fr/. 

PMID- 26313381
TI  - Melatonin: a universal time messenger.
AB  - Temporal organization plays a key role in humans, and presumably all species on
      Earth. A core building block of the chronobiological architecture is the master
      clock, located in the suprachi asmatic nuclei [SCN], which organizes "when"
      things happen in sub-cellular biochemistry, cells, organs and organisms,
      including humans. Conceptually, time messenging should follow a 5 step-cascade.
      While abundant evidence suggests how steps 1 through 4 work, step 5 of "how is
      central time information transmitted througout the body?" awaits elucidation.
      Step 1: Light provides information on environmental (external) time; Step 2:
      Ocular interfaces between light and biological (internal) time are intrinsically
      photosensitive retinal ganglion cells [ipRGS] and rods and cones; Step 3: Via the
      retinohypothalamic tract external time information reaches the light-dependent
      master clock in the brain, viz the SCN; Step 4: The SCN translate environmental
      time information into biological time and distribute this information to numerous
      brain structures via a melanopsin-based network. Step 5: Melatonin, we propose,
      transmits, or is a messenger of, internal time information to all parts of the
      body to allow temporal organization which is orchestrated by the SCN. Key reasons
      why we expect melatonin to have such role include: First, melatonin, as the
      chemical expression of darkness, is centrally involved in time- and timing
      related processes such as encoding clock and calendar information in the brain;
      Second, melatonin travels throughout the body without limits and is thus a
      ubiquitous molecule. The chemial conservation of melatonin in all tested species
      could make this molecule a candidate for a universal time messenger, possibly
      constituting a legacy of an all-embracing evolutionary history. 

PMID- 26313382
TI  - Effects of LPS injection on the hypothalamic and testicular mRNA expression
      levels of reproductive factors in male rats.
AB  - OBJECTIVES: In the hypothalamus, kisspeptin and RFamide-related peptide (RFRP)
      regulate gonadotropin-releasing hormone expression. Kisspeptin and RFRP are also
      found in the testes and might play roles in steroidogenesis and spermatogenesis.
      DESIGN AND RESULTS: The present study demonstrated that the hypothalamic mRNA
      expression level of the kisspeptin receptor was decreased by the injection of
      lipopolysaccharide (LPS) (500 MUg/kg) in male rats, and it was suggested that
      such changes might contribute to reductions in serum luteinizing hormone levels.
      Contrary to our expectations, hypothalamic RFRP and testicular GPR147 (the RFRP
      receptor) mRNA expression were also decreased by LPS injection. CONCLUSIONS: We
      speculate that changes in hypothalamic RFRP expression might represent a
      protective response aimed at attenuating LPS-induced anorectic responses.

PMID- 26313383
TI  - Intentional updating in episodic memory: Low testosterone associates with
      enhanced memory updating.
AB  - OBJECTIVES: Although there is consensus that sex hormones modulate memory, we
      have an incomplete understanding of their role in remembering and forgetting.
      Humans continuously update memory, forgetting old, out-of-date information and
      encoding new, more relevant information. Updating processes can be studied with
      the list method of directed forgetting. METHODS: In the list method of directed
      forgetting task, subjects study two lists of items and, after study of list 1,
      are asked to either forget or remember the list for an upcoming memory test. Free
      testosterone level was quantified from saliva samples. Directed forgetting and
      saliva testosterone were evaluated in young men (aged between 18 and 28 years).
      RESULTS: Following a forget cue, recall of list-1 items was reduced and recall of
      list-2 items was enhanced. However, only recall of list-2 items was associated
      with free testosterone level. Following a forget cue, participants with low
      testosterone levels showed higher recall of list-2 items than participants with
      high testosterone levels. CONCLUSION: The selective association between
      testosterone level and list-2 recall is consistent with two-mechanism accounts of
      memory updating, where the forgetting effect is due to impaired retrieval and the
      enhancement effect to improved encoding. On the basis of this view, the present
      results indicate that low testosterone levels are associated with improved
      binding of the newly encoded memories to their context cue.

PMID- 26313384
TI  - Ectopic Cushing's syndrome in light of modern diagnostic techniques and treatment
      options.
AB  - Ectopic adrenocorticotropic hormone secretion (EAS) is responsible for
      approximately 10-15% cases of Cushing's syndrome. EAS is associated with various
      tumors such as small cell lung cancer and well-differentiated bronchial or
      gastrointestinal neuroendocrine tumors. Hormonal diagnostics include assessments
      in basic conditions as well as dynamic tests, such as the high-dose dexamethasone
      suppression test and corticotrophin releasing hormone (CRH) stimulation test.
      Treatment selection depends on the type of tumor and its extent. In the case of
      neuroendocrine tumors, the main treatments are surgery and administration of
      somatostatin analogs that may be additionally radiolabeled for targeted
      radiotherapy. The tumor histology and the presence and control of
      hypercortisolemia and metastases are of major importance in prognosis. In this
      article we presented the principles of modern hormonal and imaging diagnostics
      techniques as well as the key issues associated with treatment of ACTH-dependent
      Cushing's syndrome due to EAS. 

PMID- 26313385
TI  - Poor responders in IVF--is there any evidence-based treatment for them?
AB  - Despite the vast experience in controlled ovarian hyperstimulation, there are
      still women who respond poorly to gonadotropins, which results in few oocytes at
      retrieval, reduced number of embryos for transfer and consequently unsatisfactory
      pregnancy rates. Although such patients are quite common in IVF practice, the
      exact prevalence of so-called "poor responders" is difficult to estimate due to
      the variety of applied definitions. The urgent need for an internationally
      accepted definition of poor ovarian response (POR) was addressed by an ESHRE
      Workshop held in Bologna in 2010, where the consensus was reached and criteria
      were finally established. The application of this uniform definition may allow a
      correct estimate of POR prevalence and, what is more important, designing proper
      trials to assess and finally compare the interventions used in POR patients. The
      article describes the possible physiology of POR and patient characteristics,
      mentions risk factors and laboratory tests of decreased ovarian reserve. Finally
      it reviews the possible management of POR with different stimulation protocols in
      the light of EBM. Basing on published meta-analyses, various additional
      alternatives (such as estradiol priming, the addition of rLH, growth hormone,
      androgens and androgen-modulating agents, aspirin) are also summarized. Despite
      the two decades of trying, there is still no consensus on what is best for POR.
      No single treatment can be recommended over another, as the evidence for all of
      them is insufficient. It is obvious that interventions used in POR require
      properly designed large randomized studies, because until now there is no
      evidence-based treatment for that particular group of patients. 

PMID- 26313386
TI  - What fMRI can tell as about panic disorder: bridging the gap between neurobiology
      and psychotherapy.
AB  - Fifty years ago, when the effect of antidepressants on panic disorder was
      described, a significant progress in understanding this anxiety disorder has been
      made. Theoretical mechanisms and models of fear and panic disorder were proposed
      and tested in animal models and humans. With growing possibilities of non
      invasive neuroimaging techniques, there is an increasing amount of information on
      the panic disorder. Unfortunately, a number of circumstances lead to inconsistent
      findings and its interpretations. In our review, we focused on functional MRI in
      panic disorder, limitations of current studies, possible interpretations and
      proposals for future direction. In our opinion, the current findings support the
      neuroanatomical model of panic disorder at the level of group data analysis. But
      at the same time, the results suggest significant inter-individual differences
      across the patients, which may be related to each patient's individual history,
      woven into their neural network and affecting the individual symptoms and
      response to therapy. 

PMID- 26313387
TI  - Narcolepsy with cataplexy and Parkinson's disease. Case Report.
AB  - We present the case of an 86 year old female, in whom narcolepsy with cataplexy
      (NC) manifested at 52 years of age. She was treated by an amphetamine-like drug
      phenmetrazine and tricyclic antidepressants for more than 10 years. Hypokinetic
      rigid syndrome manifested at 83 years of age and Parkinson's disease (PD) was
      diagnosed. Detailed examination at the age of 86 confirmed the previous diagnosis
      of NC and the diagnosis of PD. Severe periodic limb movements in sleep, severe
      sleep apnea, REM sleep behavior disorder and restless legs syndrome, which are
      frequently comorbid in NC and PD, were revealed. The patient's somnolence
      worsened, apparently accentuated by pramipexole treatment, as changing therapy to
      levodopa led to a reduction of sleepiness. 

PMID- 26313388
TI  - Minimal access spinal technologies (MAST) fusion procedures for the treatment of
      the degenerative lumbar spine (a part of multicentral prospective study). Case
      Report.
AB  - A prospective multicentral observational study of minimally invasive fusion to
      treat degenerative lumbar disorders, and to report outcomes of one or two level
      minimally invasive posterior lumbar interbody fusion (MLIF) for degenerative
      lumbar disorders in a multi-center 1-year prospective study. We prospectively
      studied a group of 32 patients, mostly female 24 (75% female), and 8 males (25%).
      They underwent minimally invasive transforaminal lumbar interbody fusion (mTLIF),
      21 of them monosegmental and 11 bisegmental. Patients demographics, intra
      operative data and complications were recorded. Time to first ambulation, time to
      study-defined recovery, surgical duration, blood loss, fluoroscopy time and
      adverse events were recorded. Visual analogue scale (VAS) of back and legs pain,
      Oswestry disability index (ODI) and health-related questionnaire (EQ-5D) were
      assessed preoperatively and at defined time points through 12 months
      postoperatively. Mean surgical duration, blood loss and intraoperative
      fluoroscopy time were 125 vs. 175 minutes, 150 vs. 170 ml, and 105 vs. 145
      seconds in one- and two-level segments, respectively. Mean preoperative VAS back
      (6.5) and VAS leg (7.9) scores dropped significantly (p<0.0001) to 3.5 (2.6) and
      2.6 (2.0) at discharge (6 weeks). At the end, this is the largest prospective
      multi-center observational study of MLIF to date, following routine local
      standard of practice and, MLIF demonstrated favourable clinical results with
      early and sustained improvement in patient reported outcomes and low major
      perioperative morbidity. 

PMID- 26313389
TI  - Atypical cardiac myxoma in the course of Carney complex in the child. Case
      Report.
AB  - Cardiac tumors in infants and children are rare. Myxomas are the second (after
      rhabdomyomas) most common primary cardiac tumors in pediatric patients. Cardiac,
      cutaneous and mucous myxomas are likewise the second most frequent manifestation
      of the Carney complex, an autosomal dominant multi neoplasia syndrome, which
      consists of myxomas in different locations, spotty skin pigmentation and
      endocrine overactivity. We present a case of 13-years-old boy send to our
      department from a district hospital because of the large tumor in the right
      atrium discovered in the echo study. On admission he presented discrete signs of
      Cushing's syndrome and scarse pigmented nevi on the face and trunc. The detailed
      echo examination showed the large right atrial tumor with features of myxoma,
      protruding across the tricuspid valve into the right ventricle during diastolic
      period. Atypical location of cardiac myxoma as well as the signs of Cushing's
      syndrome suggested Carney's complex. Detailed endocrine studies confirmed the
      hypothesis. Thus two-step bilateral adrenalectomy was planned. The
      histopathologic study confirmed primary pigmented nodular adrenocortical disease.

PMID- 26313390
TI  - Uterine torsion in pregnancy. Case Report.
AB  - This paper describes a case of uterine torsion not only around the long, but also
      the horizontal axis, diagnosed post-operatively. The patient was 28-years-old,
      II/I in the 34th week of her gravidity. She was admitted due to amniotic fluid
      leak. Due to unsuccessful delivery induction using prostaglandins, a caesarean
      section was indicated to end the gravidity. Uterine torsion 180 degrees  around
      the longitudinal axis and 90 degrees  around the transversal axis was diagnosed
      during the surgery. The uterine wound was treated in accordance with guidelines
      and the patient was dismissed in a good condition. Control hysteroscopy and
      laparoscopy done after a time interval showed problem-free healing of the wound
      in the posterior uterine wall. 

PMID- 26313391
TI  - Pregnancy and delivery in Leyden-Mobius muscular dystrophy. Case Report.
AB  - Leyden-Mobius muscular dystrophy is an autosomal recessive hereditary disease of
      unknown aetiology; it is a congenital disorder of protein metabolism primarily
      affecting proximal muscle groups leading to progressive muscular dystrophy. It
      later spreads to the muscles of the pelvic floor and lower extremities. The
      estimated incidence is 1:200,000. This paper describe a case of pregnancy and
      delivery in woman with progressive Leyden-Moebius muscular dystrophy. Cesarean
      section was performed due to progression of the underlying disease. First
      postoperative day DIC occure and surgical revision of abdominal cavity was
      performed. Although the uterine suture was strong, diffuse bleeding was present.
      Blood was not coagulating. Supravaginal amputation of the uterus was performed
      including left-sided adnexectomy due to bleeding from the left ovarium. Due to
      the severity of the condition and assumed necessity of long-term controlled
      ventilation, the patient was transferred to the intensive medicine department.
      She was dismissed home after 91 days of hospitalisation. Gravidity in advanced
      muscular dystrophy is rare and associated with a high risk. Due to muscle
      weakness, diaphragm weakness, atrophy of individual muscle groups, spine
      deformities and often dislocation of thoracic organs, these patients cannot avoid
      the caesarean section to end their pregnancy, followed by prolonged intubation
      and controlled ventilation. During pregnancy, the growing uterus elevates the
      diaphragm and impairs breathing. Therefore, pregnancies in such patients will
      probably always have to be ended prematurely. 

PMID- 26313392
TI  - Cerebellar ataxia induced by 3-AP affects immunological function.
AB  - OBJECTIVE: We previously showed that the cerebellum modulates the immune system.
      Here we determined whether cerebellar ataxia alters immunological function to
      further demonstrate an involvement of the cerebellum in immune modulation.
      METHODS: Neurotoxin 3-acetylpyridine (3-AP) was intraperitoneally injected in
      rats to induce cerebellar ataxia. Behavior and motor coordination were tested on
      day 7 following 3-AP injection. Nissl staining and high-performance liquid
      chromatography (HPLC) were used to determine neuronal loss and neurotransmitter
      contents, respectively, in all the three cerebellar nuclei, fastigial nucleus
      (FN), interposed nucleus (IN) and dentate nucleus (DN). T and B lymphocyte
      differentiation and function were measured by flow cytometry, Western blot and
      ELISA. RESULTS: 3-AP induced motor discoordination and locomotor reduction. In
      all the three cerebellar nuclei, FN, IN and DN, there was a neuronal loss and a
      decrease in contents of glutamate and GABA (but not glycine) after 3-AP
      injection. Importantly, CD4+ T cells, but not CD8+ T cells, were increased by the
      3-AP treatment. Moreover, interferon (IFN)-gamma-producing cells and interleukin
      (IL)-17-producing cells were decreased in cerebellar ataxia rats, but IL-4
      producing cells and CD25-expressing cells were increased. Expression of the T
      helper (Th)1- and Th17-related cytokines, IFN-gamma, IL-2, IL-17 and IL-22, was
      downregulated in CD4+ cells in cerebellar ataxia rats, while expression of the
      Th2 and regulatory T (Treg)-related cytokines, IL-4, IL-5, IL-10 and transforming
      growth factor (TGF)-beta, was upregulated. Furthermore, B lymphocyte number and
      anti-bovine serum albumin (BSA) IgM and IgG antibody levels were elevated in
      cerebellar ataxia. CONCLUSION: Cerebellar ataxia alters cellular and humoral
      immunity.

PMID- 26313393
TI  - Two methods of cervix ripening: intracervical Foley catether and dinoprostone -
      which one is actually more efficient?
AB  - OBJECTIVE: The aim was to evaluate which of the two analyzed methods of
      preinduction: intracervical Foley catether and intracervical dinoprostone is
      related to higher rate of successful vaginal delivery in shorter time and to
      shorter hospitalization after the delivery. DESIGN: A retrospective analysis of
      198 patients with unfavorable cervix for labor induction (Bishop score <= 6),
      hospitalized at 1st Department of Obstetrics and Gynecology, Medical University
      of Warsaw, was carried out. In 105 patients labor preinduction was conducted with
      Foley catheter (study group) and in 93 with intracervical dinoprostone (control
      group). RESULTS: There were no significant differences regarding patients' age,
      body mass index (BMI), weight gain during the pregnancy, duration of pregnancy
      and parity between the groups. 68.6% of patients in the study group and 65.6% in
      the control group delivered vaginally (p=0.65). In the study group significantly
      less women developed spontaneous onset of labor (36.2% vs 66.7%; p<0.001). The
      time from preinduction to delivery onset and from preinduction to vaginal
      delivery were longer in the study group (780 min vs 489 min; 1682 min vs 920 min;
      p<0.001). The time of hospitalization after the delivery was significantly
      shorter in the study group (4.1 days vs 6.8; (p<0.001). CONCLUSION: Both Foley
      catheter and dinoprostone seem to be equally effective in achieving vaginal
      delivery. In terms of time effectiveness Foley catheter preinduction is related
      to longer time from preinduction to delivery, nevertheless shorter time of
      hospitalization.

PMID- 26313394
TI  - The ABCD2 score may underestimate the short-term risk of stroke in Chinese
      population: A meta-analysis.
AB  - OBJECTIVES: The ABCD2 score has been commonly used to triage patients with
      transient ischemic attack (TIA) who are at high risk for imminent stroke.
      However, its accuracy in predicting short-term stroke risk among TIA patients in
      China remains unclear. METHODS: All eligible studies published up to May 2014
      were identified by searching Medline, PubMed, Embase, the China Knowledge
      Resource Integrated Database (CNKI) and the China Biological Medicine Database
      (CBM-disc), as well as unpublished articles manually scanned. The strength of the
      associations between treatments and outcomes was estimated by incorporated risk
      ratios (RRs) and 95% confidence intervals (CIs) using the Mantel-Haenszel
      statistical method. RESULTS: Eight and 32 studies, which validated the value for
      predicting the risk of stroke 2 and 7 days after TIA respectively, were included.
      We calculated the RRs and CIs for 2- and 7-day prediction for stroke (low:
      RR=0.43, 95% CI=0.17-1.10, I2=0%; moderate: RR=0.42, 95% CI=0.26-0.67, I2=0%;
      high: RR=0.32, 95% CI=0.21-0.48, I2=0%; and low: RR=0.29, 95% CI=0.20-0.44,
      I2=0%; moderate: RR=0.27, 95% CI=0.23-0.33, I2=0%; high: RR=0.22, 95% CI=0.18
      0.27, I2=1%). CONCLUSIONS: This meta-analysis indicated that the ABCD2 score may
      highly under-predict the short-term occurrence of stroke after TIA for the
      Chinese population compared with the original model derived from Caucasian
      populations, which may lead to neglect of the short-term risk for stroke in the
      clinical practice.

PMID- 26313395
TI  - Predictors of poor treatment response to additional CBT in real panic disorder
      patients: The role of DLPF, orbitofrontal cortex, parietal lobule, frontal eye
      field and amygdala in PD.
AB  - OBJECTIVE: Previous functional brain imaging studies have described various and
      contradictory activation findings in patients with panic disorder (PD). Our study
      focused on patients with a chronic PD, who were investigated and treated in a
      conventional manner, which represents the real PD patients in clinical practice.
      METHODS: Continuing their medication, patients were included in a six-week
      cognitive-behavioral therapy (CBT) program in the psychiatry department. At the
      onset of the study, participants underwent clinical evaluation using standard
      scales and were examined using fMRI while listening to verbal threat-related
      stimuli contrasted to neutral words. According to the therapeutic outcome, they
      were subsequently divided into two groups, responders, and nonresponders and the
      two groups were mutually compared. RESULTS: In non-responders compared to
      responders, we found increased pre-treatment activation in dorsolateral
      prefrontal cortex bilaterally, left orbitofrontal cortex, left frontal eye field,
      right parietal lobule and left amygdala. In addition, both groups showed negative
      fMRI BOLD correlation with BAI improvement and positive correlation with CGI
      improvement across the ROIs. We suggest that DLPFC over-activation may reveal a
      lack of cognitive control over emotional processing, which makes subsequent CBT
      less effective. CONCLUSION: Despite several limitations, we found neuroimaging
      predictors of poor CBT response, under the conditions of standard clinical
      practice, in real PD patients.

PMID- 26313396
TI  - Association of single nucleotide polymorphism rs7579169 with hypertension
      disorders during pregnancy and perinatal outcome.
AB  - BACKGROUND: Hypertension during pregnancy is a heterogeneous group of disorders
      with elevated blood pressure with or without proteinuria. The multiple researches
      are held on the subject of a genetic conditioning of preeclampsia and pregnancy
      induced hypertension. OBJECTIVES: The study was designed to evaluate the impact
      of the single nucleotide polymorphism (SNP) rs7579169 on hypertension disorders
      in pregnancy, especially on PE and PIH as well as on the perinatal outcome.
      METHODS: It is a case-control study. The study included 104 women with
      uncomplicated pregnancies in the control group and 75 pregnant women with
      hypertension disorders in the study group, hospitalized in the Perinatology and
      Obstetrics Department of the University Hospital in Cracow. Genomic DNA was
      extracted from peripheral blood leukocytes and SNP rs7579169 was genotyped from
      all patients. We analyzed the genotypes distribution and allele frequencies of
      polymorphism rs7579169 and its association with perinatal outcome in all groups.
      A p-value<0.05 was considered as significant. RESULTS: Clinical evaluation
      included standard anthropometric measures like weight and height for the
      calculation of the body mass index in the beginning and in the end of the
      pregnancy, blood pressure, time and a method of delivery, birth weight, Apgar
      score. The heterozygote CT was associated with a 4.5-fold increased risk of
      preeclampsia in pregnant patients. The presence of TT genotype significantly
      increased the risk of intrauterine growth restriction (<10 percentile).
      CONCLUSIONS: The study show probable impact of SNP rs7579169 on pregnancy, but
      further studies on larger groups are needed.

PMID- 26313397
TI  - Quality of life and needs of hospitalized schizophrenic patients in the Czech
      Republic.
AB  - OBJECTIVES: The main aim of the study was to investigate the quality of life and
      the medicinal and social needs of patients hospitalized with schizophrenia in the
      Czech Republic to uncover potential issues in these areas. METHODS: Relevant self
      evaluating questionnaires (SQUALA for quality of life; CANSAS for medicinal and
      social needs) were used in a cohort of hospitalized schizophrenic patients
      undergoing rehabilitation before discharge from the mental hospital. RESULTS: Two
      hundred and forty-four patients (women N=115) aged 18-58 years were involved in
      the study. The quality of life of hospitalized patients with schizophrenia was
      subjectively assessed as universally worse in comparison with the general Czech
      population (p<0.05 in most cases; two-sample Student's t-test), but patients were
      not wholly critical of their own health status and overestimated its quality
      (arithmetic mean 63.79 in the patients vs the range of 45.5-59.8 as the norm in
      the general Czech population). Intimate relations, financial matters, treatment
      of psychotic symptoms, and sexual life were among the most pressing medicinal and
      social needs in our study subjects. CONCLUSION: The results of our study should
      stimulate psychiatric nurses in their effort not only to detect but also address
      the problems of schizophrenic patients concerning quality of life and unfulfilled
      needs. This can be done via education, guidance towards a healthy lifestyle, or
      providing patients with adequate exercise. Overall this issue is of significant
      importance in the Czech Republic due to the fact that legislative reform of
      mental health care emphasizing community care and psychiatric nursing has just
      been implemented.

PMID- 26313398
TI  - Association of arterial hypertension and cognitive impairment in euthymic bipolar
      disorder.
AB  - OBJECTIVES: Cognitive impairment in euthymic phase of bipolar disorder has been
      documented in many studies. Several factors may contribute to such impairment,
      e.g. sedative medication, thyreopathy. Metabolic syndrome with its components
      represents another frequent condition found in bipolar disorder exerting probably
      adverse impact on cognition. Since it is treatable factor and current literature
      suggests possible connection with cognitive dysfunction, we aimed to explore such
      associations to identify promising targets of complex treatment. METHODS: Forty
      euthymic bipolar patients have been enrolled. Their body and metabolic parameters
      were measured. Medical history data were collected. Cognition was evaluated using
      battery of tests. Neuropsychological performance was transformed into
      neurocognitive composite score. Cognition of subjects was compared dichotomously
      according to presence or absence of pathological body and metabolic parameters.
      Correlations of selected parameters and composite score were done. RESULTS: Low
      neurocognitive score was found in presence of hypertension, metabolic syndrome,
      abdominal obesity and hyperglycemia. Only connection of hypertension and
      cognitive score reached sufficient statistical power. Patients presenting
      hypertension performed worse in all tested domains of cognition when compared
      with normal blood pressure group. Subjects using lithium performed substantially
      worse in cognitive tests. However, in comparison with anticonvulsant group,
      lithium users had markedly longer disorder history as well as longer duration of
      thymoprofylaxis. No significant correlation of HDRS score, insulinemia or HOMA-IR
      was found. CONCLUSION: Despite relatively small sample size, noticeable
      association of hypertension and cognitive impairment was revealed. This might
      indicate possible way of enhancing cognition in bipolar disorder by treating
      elevated blood pressure.

PMID- 26313399
TI  - A bio-inspired sensor coupled with a bio-bar code and hybridization chain
      reaction for Hg(2+) assay.
AB  - In this article, a bio-inspired DNA sensor is developed, which is coupled with a
      bio-bar code and hybridization chain reaction. This bio-inspired sensor has a
      high sensitivity toward Hg(2+), and has been used to assay Hg(2+) in the
      extraction of Bauhinia championi with good satisfaction. 

PMID- 26313400
TI  - Effectiveness of case finding strategies for COPD in primary care: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is widely
      underdiagnosed, but the most effective approach for identifying these patients is
      unknown. AIMS: The aim of this study was to summarise and compare the
      effectiveness of different case finding approaches for undiagnosed COPD in
      primary care. METHODS: A systematic review of primary studies of any design
      evaluating case finding strategies for COPD in primary care among individuals
      aged ?35 years with no prior diagnosis was conducted. Medline, Embase and other
      bibliographic databases were searched from 1997 to 2013, and methodological
      quality was assessed using standard tools. Results were described and meta
      analysis of the uptake and yield from different approaches was performed where
      there was sufficient homogeneity. RESULTS: Three randomised controlled trials
      (RCTs), 1 controlled trial and 35 uncontrolled studies were identified that
      assessed the identification of new cases of COPD through systematic case finding.
      A range of approaches were used including pre-screening with questionnaires
      (n=13) or handheld flow meters (n=5) or direct invitation to diagnostic
      spirometry (n=30). Overall, any approach identified more undiagnosed COPD
      compared with usual care. Targeting those at higher risk (e.g., smokers) and pre
      screening (e.g., using questionnaires) is likely to increase the yield. However,
      studies were heterogeneous and were limited by a lack of comparison groups,
      inadequate reporting and diversity in the definition of COPD, which limited our
      ability to draw firm conclusions. CONCLUSIONS: There is extensive heterogeneity
      among studies evaluating case finding strategies for COPD, with few RCTs. Well
      conducted RCTs comparing case finding approaches are needed to identify the most
      effective target population, recruitment strategy and screening tests, using a
      clinical definition of COPD, and addressing the limitations highlighted in this
      review. There is also a need to evaluate the impact of case finding on clinical
      care and patient outcomes.

PMID- 26313401
TI  - Systematic review and meta-analysis of the possible association between
      pharmacological gastric acid suppression and spontaneous bacterial peritonitis.
AB  - BACKGROUND: Observational studies have presented conflicting results with regard
      to an association between gastric acid suppression and spontaneous bacterial
      peritonitis (SBP). Our aim was to carry out a meta-analysis investigating the
      possible association between the use of proton pump inhibitors or H2-receptor
      antagonists and SBP. METHODS: We searched several databases from inception
      through 15 December 2014 to identify observational studies that provided data on
      the association of gastric acid suppression with SBP as their primary outcome,
      and carried out random effects meta-analyses. RESULTS: Fourteen observational
      studies (six case-control and eight cohort) evaluating the association between
      proton pump inhibitors and SBP revealed a pooled odds ratio (OR) of 2.32 [95%
      confidence interval (CI) 1.57-3.42, I(2)=82%]. The subgroup analysis based on
      study design revealed a pooled OR of 2.52 (95% CI 1.71-3.71, I(2)=16%) for case
      control studies, and a pooled OR of 2.18 (95% CI 1.24-3.82, I(2)=89%) for cohort
      studies. Sensitivity analysis including only the peer-reviewed publications in
      the cohort subgroup revealed a pooled OR of 1.49 (95% CI 1.15-1.95, I(2)=27%).
      The subgroup analysis for high-quality studies revealed a pooled OR of 1.49 (95%
      CI 1.19-1.88, I(2)=21%). The pooled OR for H2-receptor antagonists and SBP was
      1.93 (95% CI 1.15-3.24, I(2)=0%). CONCLUSIONS: There appear to be statistically
      significant, but quantitatively small, associations between gastric acid
      suppression and SBP. However, the magnitude of the possible association
      diminished when analysis focused on higher quality data that were more robust.
      Furthermore, the quality evidence in support of the association, as per the GRADE
      framework, was very low.

PMID- 26313402
TI  - Safety of Microfocused Ultrasound With Visualization in Patients With Fitzpatrick
      Skin Phototypes III to VI.
AB  - IMPORTANCE: A microfocused ultrasound (MFU) system is a safe and effective
      aesthetic treatment for tightening and lifting skin in the facial and neck areas.
      This open-label, nonrandomized trial was performed to further demonstrate the
      safety of MFU for improving laxity of the skin of the face and neck in 52 adults
      with Fitzpatrick skin types III to VI. OBSERVATIONS: Before treatment with MFU,
      the skin tissue of each participant was assessed and ultrasound imaging was
      performed on the treatment area to ensure appropriate acoustic transducer
      coupling. Treatment was performed from March 23, 2011, to July 20, 2011.
      Following treatment, there were 3 reported adverse events described as raised
      areas of mild edema or welts (2 events) and moderately severe prolonged erythema
      with mild scabbing (1 event). All events resolved after 90 days without sequelae.
      Analysis was conducted from Janaury 18, 2012, to March 13, 2013. CONCLUSIONS AND
      RELEVANCE: The adverse events that occurred in this trial were temporary and
      associated with treatment technique. When performed by trained physicians, MFU is
      safe in patients with Fitzpatrick skin types III to VI. LEVEL OF EVIDENCE: 4.
      TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01368965.

PMID- 26313403
TI  - A urologist's contemporary guide to penile cancer.
AB  - Few urologists deal with penile cancer on a daily basis. Owing to the rarity of
      the disease and its diversity in presentation, clinical experience accumulates
      slowly and new paradigms spread sporadically. This review provides a concise
      update on the background, clinical features and multidisciplinary management
      strategies of penile cancer. The evidence base of penile cancer management
      recommendations is devoid of randomized controlled trials and relies mainly on
      retrospective cohort studies from single institutions. In recent years,
      international multicentre collaboration has increased the quality of evidence.
      Larger study cohorts allow researchers to engage in subgroup analysis of patients
      with poor prognosis, of which the literature so far has been scarce.
      Comprehensive evidence-based guidelines are available through the European
      Association of Urology. This review highlights the importance of early and
      minimally invasive regional lymph-node staging of all patients of stage T1G2 or
      higher, and underlines the therapeutic potential of inguinal lymph-node
      dissection in lymph-node positive patients. A discussion of the oncological
      safety of current trends towards more phallus-sparing treatment techniques
      emphasizes the importance of proper case selection, thorough patient information,
      consequent follow-up and the possibility of a reconstructive procedure after
      organ-sparing ablative penile surgery. The aetiological role of human papilloma
      virus (HPV) is touched upon and the evidence for circumcision and HPV vaccination
      of boys is briefly weighed. The value of multidisciplinary treatment of advanced
      penile cancer is underlined and the role of chemotherapy, radiotherapy and
      radiochemotherapy is discussed. Finally, the perspectives for hybrid tracer
      sentinel node, robot-assisted lymph-node surgery and targeted therapies are
      addressed.

PMID- 26313404
TI  - Comparison of transforaminal lumbar interbody fusion performed with unilateral
      pedicle screw fixation or unilateral pedicle screw-contralateral percutaneous
      transfacet screw fixation.
AB  - PURPOSE: To determine whether unilateral pedicle screw fixation is comparable
      with unilateral pedicle screw and contralateral percutaneous transfacet screw
      fixation in single-level lumbar spinal fusion. METHODS: Fifty-eight patients were
      divided into either unilateral (n = 32) or unilateral pedicle screw and
      contralateral percutaneous transfacet screw fixation (n = 26) instrumentation
      groups. The operating time, blood loss, length of hospital stay, clinical
      outcomes, total lumbar scoliotic changes, and fusion and complication rates were
      compared between the two groups. RESULTS: There were no significant differences
      between the two groups in blood loss, length of hospital stay, clinical results,
      total lumbar scoliotic changes, and fusion and complication rates. There were
      significant differences in duration of operating time between 2 groups.
      CONCLUSIONS: Unilateral pedicle screw fixation may be as effective as unilateral
      PS with contralateral percutaneous transfacet screw fixation for the treatment of
      lumbar degenerative disorders.

PMID- 26313405
TI  - Role of adult hippocampal neurogenesis in persistent pain.
AB  - The full role of adult hippocampal neurogenesis (AHN) remains to be determined,
      yet it is implicated in learning and emotional functions, and is disrupted in
      negative mood disorders. Recent evidence indicates that AHN is decreased in
      persistent pain consistent with the idea that chronic pain is a major stressor,
      associated with negative moods and abnormal memories. Yet, the role of AHN in
      development of persistent pain has remained unexplored. In this study, we test
      the influence of AHN in postinjury inflammatory and neuropathic persistent pain
      like behaviors by manipulating neurogenesis: pharmacologically through
      intracerebroventricular infusion of the antimitotic AraC; ablation of AHN by x
      irradiation; and using transgenic mice with increased or decreased AHN.
      Downregulating neurogenesis reversibly diminished or blocked persistent pain;
      oppositely, upregulating neurogenesis led to prolonged persistent pain. Moreover,
      we could dissociate negative mood from persistent pain. These results suggest
      that AHN-mediated hippocampal learning mechanisms are involved in the emergence
      of persistent pain. 

PMID- 26313407
TI  - Healthy and normal? The need for clear reporting and flexible criteria for
      defining control participants in quantitative sensory testing studies.

PMID- 26313406
TI  - Exercise prevents development of autonomic dysregulation and hyperalgesia in a
      mouse model of chronic muscle pain.
AB  - Chronic musculoskeletal pain (CMP) conditions, like fibromyalgia, are associated
      with widespread pain and alterations in autonomic functions. Regular physical
      activity prevents the development of CMP and can reduce autonomic dysfunction. We
      tested if there were alterations in autonomic function of sedentary mice with
      CMP, and whether exercise reduced the autonomic dysfunction and pain induced by
      CMP. Chronic musculoskeletal pain was induced by 2 intramuscular injections of pH
      5.0 in combination with a single fatiguing exercise task. A running wheel was
      placed into cages so that the mouse had free access to it for either 5 days or 8
      weeks (exercise groups) and these animals were compared to sedentary mice without
      running wheels. Autonomic function and nociceptive withdrawal thresholds of the
      paw and muscle were assessed before and after induction of CMP in exercised and
      sedentary mice. In sedentary mice, we show decreased baroreflex sensitivity,
      increased blood pressure variability, decreased heart rate variability, and
      decreased withdrawal thresholds of the paw and muscle 24 hours after induction of
      CMP. There were no sex differences after induction of the CMP in any outcome
      measure. We further show that both 5 days and 8 weeks of physical activity
      prevent the development of autonomic dysfunction and decreases in withdrawal
      threshold induced by CMP. Thus, this study uniquely shows the development of
      autonomic dysfunction in animals with chronic muscle hyperalgesia, which can be
      prevented with as little as 5 days of physical activity, and suggest that
      physical activity may prevent the development of pain and autonomic dysfunction
      in people with CMP. 

PMID- 26313409
TI  - Coordination of seed dormancy and germination processes by MYB96.
AB  - The transition between seed dormancy and germination is an important stage that
      initiates plant life cycle. Hormonal balances of abscisic acid (ABA) and
      gibberellin (GA) contribute to determining the proper timing to germinate. Here,
      we demonstrate that the R2R3-type MYB96 transcription factor, a key ABA signaling
      mediator, coordinates seed dormancy and germination processes through distinct
      downstream events. This transcription factor controls ABA-INSENSITIVE 4 (ABI4)
      expression to inhibit seed germination by suppressing breakdown of lipid reserves
      in embryo. In addition, it also induces seed dormancy by stimulating ABA
      biosynthesis in an ABI4-independent manner. We propose that MYB96 integrates a
      multitude of environmental stress signals and acts as a master regulator in the
      determination of timing for seed germination. 

PMID- 26313408
TI  - Different phosphoinositide 3-kinase isoforms mediate carrageenan nociception and
      inflammation.
AB  - Phosphoinositide 3-kinases (PI3Ks) participate in signal transduction cascades
      that can directly activate and sensitize nociceptors and enhance pain
      transmission. They also play essential roles in chemotaxis and immune cell
      infiltration leading to inflammation. We wished to determine which PI3K isoforms
      were involved in each of these processes. Lightly anesthetized rats (isoflurane)
      were injected subcutaneously with carrageenan in their hind paws. This was
      preceded by a local injection of 1% DMSO vehicle or an isoform-specific
      antagonist to PI3K-alpha (compound 15-e), -beta (TGX221), -delta (Cal-101), or 
      gamma (AS252424). We measured changes in the mechanical pain threshold and spinal
      c-Fos expression (4 hours after injection) as indices of nociception. Paw volume,
      plasma extravasation (Evans blue, 0.3 hours after injection), and neutrophil
      (myeloperoxidase; 1 hour after injection) and macrophage (CD11b+; 4 hour after
      injection) infiltration into paw tissue were the measured inflammation endpoints.
      Only PI3K-gamma antagonist before treatment reduced the carrageenan-induced pain
      behavior and spinal expression of c-Fos (P <= 0.01). In contrast, pretreatment
      with PI3K-alpha, -delta, and-gamma antagonists reduced early indices of
      inflammation. Plasma extravasation PI3K-alpha (P <= 0.05), -delta (P <= 0.05),
      and -gamma (P <= 0.01), early (0-2 hour) edema -alpha (P <= 0.05), -delta (P <=
      0.001), and -gamma (P <= 0.05), and neutrophil infiltration (all P <= 0.001) were
      all reduced compared to vehicle pretreatment. Later (2-4 hour), edema and
      macrophage infiltration (P <= 0.05) were reduced by only the PI3K-delta and 
      gamma isoform antagonists, with the PI3K-delta antagonist having a greater effect
      on edema. PI3K-beta antagonism was ineffective in all paradigms. These data
      indicate that pain and clinical inflammation are pharmacologically separable and
      may help to explain clinical conditions in which inflammation naturally wanes or
      goes into remission, but pain continues unabated. 

PMID- 26313410
TI  - Intra-fractional bladder motion and margins in adaptive radiotherapy for urinary
      bladder cancer.
AB  - BACKGROUND: The bladder is a tumour site well suited for adaptive radiotherapy
      (ART) due to large inter-fractional changes, but it also displays considerable
      intra-fractional motion. The aim of this study was to assess target coverage with
      a clinically applied method for plan selection ART and to estimate population
      based and patient-specific intra-fractional margins, also relevant for a future
      re-optimisation strategy. MATERIAL AND METHODS: Nine patients treated in a
      clinical phase II ART trial of daily plan selection for bladder cancer were
      included. In the library plans, 5 mm isotropic margins were added to account for
      intra-fractional changes. Pre-treatment and weekly repeat magnetic resonance
      imaging (MRI) series were acquired in which a full three-dimensional (3D) volume
      was scanned every second min for 10 min (a total of 366 scans in 61 series).
      Initially, the bladder clinical target volume (CTV) was delineated in all scans.
      The t = 0 min scan was then rigidly registered to the planning computed
      tomography (CT) and plan selections were simulated using the CTV_0 (at t = 0
      min). To assess intra-fractional motion, coverage of the CTV_10 (at t = 10 min)
      was quantified using the applied PTV. Population-based margins were calculated
      using the van Herk margin recipe while patient-specific margins were calculated
      using a linear model. RESULTS: For 49% of the cases, the CTV_10 extended more
      than 5 mm outside the CTV_0. However, in 58 of the 61 cases (97%) CTV_10 was
      covered by the selected PTV. Population-based margins of 14 mm Sup/Ant, 9 mm Post
      and 5 mm Inf/Lat were sufficient to cover the bladder. Using patient-specific
      margins, the overlap between PTV and bowel-cavity was reduced from 137 cm(3) with
      the plan selection strategy to 24 cm(3). CONCLUSION: In this phase II ART trial,
      5 mm isotropic margin for intra-fractional motion was sufficient even though
      considerable intra-fractional motion was observed. In online re-optimised ART,
      population-based margin can be applied although patient-specific margins are
      preferable.

PMID- 26313411
TI  - Haustorium Formation in Medicago truncatula Roots Infected by Phytophthora
      palmivora Does Not Involve the Common Endosymbiotic Program Shared by Arbuscular
      Mycorrhizal Fungi and Rhizobia.
AB  - In biotrophic plant-microbe interactions, microbes infect living plant cells, in
      which they are hosted in a novel membrane compartment, the host-microbe
      interface. To create a host-microbe interface, arbuscular mycorrhizal (AM) fungi
      and rhizobia make use of the same endosymbiotic program. It is a long-standing
      hypothesis that pathogens make use of plant proteins that are dedicated to
      mutualistic symbiosis to infect plants and form haustoria. In this report, we
      developed a Phytophthora palmivora pathosystem to study haustorium formation in
      Medicago truncatula roots. We show that P. palmivora does not require host genes
      that are essential for symbiotic infection and host-microbe interface formation
      to infect Medicago roots and form haustoria. Based on these findings, we conclude
      that P. palmivora does not hijack the ancient intracellular accommodation program
      used by symbiotic microbes to form a biotrophic host-microbe interface. 

PMID- 26313412
TI  - Prophage-Encoded Peroxidase in 'Candidatus Liberibacter asiaticus' Is a Secreted
      Effector That Suppresses Plant Defenses.
AB  - 'Candidatus Liberibacter asiaticus' is transmitted by psyllids and causes
      huanglongbing (HLB), a lethal disease of citrus. Most pathogenic 'Ca. L.
      asiaticus' strains carry two nearly identical prophages similar to SC1 and SC2 in
      strain UF506. SC2 was observed to replicate as a moderately high-copy excision
      plasmid encoding a reactive oxygen species-scavenging peroxidase (SC2_gp095), a
      predicted lysogenic conversion factor. SC2_gp095 was expressed at significantly
      higher levels in periwinkle than in citrus and was suppressed in psyllids.
      SC2_gp095 was cloned in a shuttle vector and transformed into Escherichia coli
      and Liberibacter crescens, a culturable proxy for 'Ca. L. asiaticus'. Transformed
      L. crescens cells showed 20 to 25% enhanced resistance to H2O2on agar plates, 47%
      greater enzymatic activity, and enhanced growth in liquid cultures. A
      nonclassical secretion potential was predicted for SC2_gp095 and secretion from
      L. crescens was confirmed by enzymatic and Western blot analyses. Transient
      expression of SC2_gp095 in planta resulted in strong transcriptional
      downregulation of RbohB, the key gatekeeper of the H2O2-mediated defense
      signaling in plants, helping explain the surprisingly long incubation period
      (years) before HLB symptoms appear in 'Ca. L. asiaticus'-infected citrus. 'Ca. L.
      asiaticus' peroxidase is likely a secreted, horizontally acquired effector that
      suppresses host symptom development, a tactic used by most biotrophic plant
      pathogens.

PMID- 26313413
TI  - Learning, assessment and professional identity development in public health
      training.
AB  - BACKGROUND: Professional identity formation is important for new recruits to
      training programmes. The integration of the accumulation of knowledge and
      assessment is a key aspect in its acquisition. This study assessed this
      interaction in Public Health Training in one English region. METHODS: Semi
      structured interviews were held with 15 registrars from the West Midlands Public
      Health Training Programme. Pre-interview questionnaires gathered background
      information. A thematic content analysis approach was taken. RESULTS: There was a
      lack of integration between academic and workplace learning, the professional
      examination process and professional identity development. Registrars considered
      sitting the examination and their workplace learning as two parallel processes.
      Passing the examination was considered a key part in the early development of a
      professional identity but this was replaced by the opinions of others by the
      third year of training. Having a Masters' in Public Health was less important but
      played a different role in their perceived acceptance by the wider Public Health
      workforce. CONCLUSION: The lack of integration between assessment and learning
      seemed to have a detrimental effect on professional identity development. A
      review of how these two aspects might combine in a more positive manner is
      needed.

PMID- 26313414
TI  - Magneto-electronic properties of graphene nanoribbons with various edge
      structures passivated by phosphorus and hydrogen atoms.
AB  - The electronic and magnetic structures of graphene nanoribbons (GNRs) with
      various edge structures passivated by P atoms are investigated systematically,
      and compared with H passivation as well. GNRs with the entire reconstructed Klein
      edge or armchair edge are found to be nonmagnetic regardless of P or H
      passivation. However, if the edge of GNRs is a mixture of zigzag edge and
      reconstructed Klein edge, they are nonmagnetic for H passivation but
      significantly magnetic for P passivation, which could be attributed to the
      "charge transfer doping" effect. And the corresponding magnetic device shows a
      noticeable negative differential resistance phenomenon and an excellent spin
      filtering effect under AP configuration, which originate from the special energy
      band structure. The GNRs with zigzag edge, reconstructed Klein edge, or mixed
      edge shapes are all metals in the nonmagnetic state regardless of the H or P
      atoms involved. The relationship between the energy gap and the width in armchair
      edged GNRs by P passivation with a dimer structure also satisfies the 3p
      periodicity, but different in detail from the case of H passivation. The
      calculated edge formation energy indicates that P-passivated GNRs are
      energetically more favorable, suggesting that they can stably exist in the
      experiment. 

PMID- 26313415
TI  - Nivolumab and pembrolizumab as immune-modulating monoclonal antibodies targeting
      the PD-1 receptor to treat melanoma.
AB  - Malignant melanoma is an important issue in oncology due to its high incidence,
      high mortality, and resistance to systemic therapy; however, targeted
      immunotherapy has noticeably improved the survival rates of melanoma patients.
      Promising targeted immunotherapies for malignant melanoma include the blockade of
      immune checkpoints with antibodies targeting cytotoxic T lymphocyte-associated
      antigen 4 and the programmed cell death protein 1 pathway. The US FDA-approved
      antibody ipilimumab targets cytotoxic T lymphocyte-associated antigen 4; however,
      it was limited by toxicity and a low response. Nivolumab and pembrolizumab
      (formerly lambrolizumab), the two FDA-approved anti-programmed death-1 monoclonal
      antibodies, show highly durable response rates and long-term safety, validating
      the importance of the programmed cell death protein 1 pathway blockade for
      treatment of malignant melanoma. 

PMID- 26313417
TI  - The role of clusterin in prostate cancer: treatment resistance and potential as a
      therapeutic target.
AB  - Resistance to cancer treatment can arise through multiple mechanisms and
      negatively impacts on progression rates and survival times. New therapies
      targeting pathways underlying resistance would improve treatment outcomes and be
      of particular value in the treatment of prostate cancer, many of whom develop
      tumors refractory to radiation, hormonal therapy and chemotherapy regimens. The
      improved understanding of metastatic castration resistant prostate cancer
      progression mechanisms has broadened the therapeutic window by unveiling multiple
      molecular targets. Several approaches are being investigated to overcome
      resistance in prostate cancer, including the use of novel taxanes and tubulin
      inhibitors, and the inhibition of cell survival pathways. This review focuses on
      clusterin, a small heat-shock-like protein that is overexpressed in many types of
      solid tumors; we summarize the preclinical and clinical evidence supporting the
      rationale for targeting clusterin as a means to resensitize prostate tumors to
      radiation and chemotherapy agents. 

PMID- 26313416
TI  - ODM-201: a new-generation androgen receptor inhibitor in castration-resistant
      prostate cancer.
AB  - Androgen deprivation therapy is the standard of care for patients with advanced
      hormone-sensitive prostate cancer. Despite an initial response, most patients
      progress to castration-resistant prostate cancer (CRPC). The realization that
      CRPC remains driven by androgen receptor (AR) signaling has formed the basis for
      a new generation of agents targeting the AR axis. Two of these agents,
      abiraterone acetate and enzalutamide, have been shown to prolong overall survival
      in patients with CRPC. Several other AR inhibitors are currently in development
      for the treatment of CRPC. The present article reviews ODM-201, a new-generation
      AR inhibitor with a unique molecular structure, in the treatment of CRPC. The
      design of an ongoing Phase III trial (ARAMIS) of ODM-201 in men with non
      metastatic CRPC is also discussed, at a disease stage for which there is
      currently no approved treatment. 

PMID- 26313418
TI  - Drug transporters in breast cancer: response to anthracyclines and taxanes.
AB  - Despite the advances that have taken place in the past decade, including the
      development of novel molecular targeted agents, cytotoxic chemotherapy remains
      the mainstay of cancer treatment. In breast cancer, anthracyclines and taxanes
      are the two main chemotherapeutic options used on a routine basis. Although
      effective, their usefulness is limited by the inevitable development of
      resistance, a lack of response to drug-induced cancer cell death. A large body of
      research has resulted in the characterization of a plethora of mechanisms
      involved in resistance; ATP-binding cassette transporter proteins, through their
      function in xenobiotic clearance, play an important role in resistance. We review
      here the current evidence for drug transporters as biomarkers and the benefit of
      adding drug transporter modulators to conventional chemotherapy. 

PMID- 26313419
TI  - Biomarkers and novel agents in esophago-gastric cancer: are we making progress?
AB  - Esophago-gastric cancer (EGC) provides a formidable healthcare challenge.
      Conventional chemotherapy provides modest survival benefit in patients with
      advanced disease especially in the second-line setting. The recent paradigm shift
      in the oncology community towards targeting growth factor pathways and the immune
      system using novel targeted agents has now demonstrated clinical utility in EGC,
      but recent trial results have highlighted the complexity of disease pathogenesis
      and significant challenges remain. Here, we describe the current role of targeted
      therapies in EGC, and their corresponding biomarkers. We aim to provide a
      comprehensive review of the current climate of novel agents and their biomarkers
      in advanced EGC. 

PMID- 26313420
TI  - Associations Between Mild Cognitive Impairment and Hospitalization and
      Readmission.
AB  - OBJECTIVES: To determine whether older adults with mild cognitive impairment
      (MCI), a condition not previously explored as a risk factor, have more
      hospitalizations and 30-day readmissions than those with normal cognition.
      DESIGN: Post hoc analysis of prospectively gathered data on incident
      hospitalization and readmission from the Ginkgo Evaluation of Memory Study
      (GEMS), a randomized, double-blind, placebo-controlled trial designed to assess
      the effect of Ginkgo biloba on incidence of dementia. SETTING: GEMS was conducted
      in five academic medical centers in the United States. PARTICIPANTS: Community
      dwelling adults aged 75 and older with normal cognition (n = 2,314) or MCI (n =
      428) at baseline cognitive testing (N = 2,742). MEASUREMENTS: Index
      hospitalization and 30-day hospital readmission, adjusted for age, sex, race,
      education, clinic site, trial assignment status, comorbidities, number of
      prescription medications, and living with an identified proxy. RESULTS: MCI was
      associated with a 17% greater risk of index hospitalization than normal cognition
      (adjusted hazard ratio (aHR) = 1.17, 95% confidence interval (CI) = 1.02-1.34)).
      In participants who lived with a proxy, MCI was associated with a 39% greater
      risk of index hospitalization (aHR = 1.39, 95% CI = 1.17-1.66). Baseline MCI was
      not associated with greater odds of 30-day hospital readmission (adjusted odds
      ratio = 0.90, 95% CI = 0.60-1.36). CONCLUSION: MCI may represent a target
      condition for healthcare providers to coordinate support services in an effort to
      reduce hospitalization and subsequent disability.

PMID- 26313421
TI  - Resistance to EGFR-targeted therapy by Ets-1 inactivation.

PMID- 26313422
TI  - Synthesis of surface protein-imprinted nanoparticles endowed with reversible
      physical cross-links.
AB  - Researches on protein molecularly imprinted polymers have been challenged by the
      difficulties in facilitating biomacromolecular transfer, in particular upon the
      template removal step, and enhancing their recognition performance. Addressing
      these issues, herein we report synthesis of core-shell structured surface protein
      imprinted nanoparticles with reversible physical cross-links formed in the
      imprinted nanoshells. The imprinted layers over nanoparticle supports are
      fabricated via aqueous precipitation polymerization (PP) of di(ethylene glycol)
      methyl ether methacrylate (MEO2MA), a thermo-responsive monomer bearing no strong
      H-bond donor, and other functional and cross-linking monomers. During
      polymerization, physical cross-links together with chemical cross-links are in
      site produced within the imprinted shells based on hydrophobic association among
      the PMEO2MA, favoring formation of high-quality imprints. While cooled
      appropriately below the polymerization temperature, these physical cross-links
      can be dissociated rapidly, thus facilitating removal of the embedded template.
      For proof of this concept, lysozyme-imprinted nanoparticles were synthesized at
      37  degrees C over the nanoparticles functionalized with carboxylic and vinyl
      groups. The template removal from the imprinted nanoparticles was readily
      achieved by washing with a dilute acidic detergent solution at 4  degrees C. As
      prepared imprinted nanoparticles showed greatly higher imprinting factor and
      specific rebinding than obtained with the same recipe but by solution
      polymerization (SP). Moreover, such imprinted nanomaterials exhibited
      satisfactory rebinding selectivity, kinetics and reusability.

PMID- 26313423
TI  - Discovery of a novel fluorescent probe for the sensitive detection of beta
      amyloid deposits.
AB  - Here we reported the development of the first photoinduced electron transfer
      (PeT) probe (1) to directly locate beta-amyloid aggregates (Abeta plaques) in the
      brain without the need of post-washing procedures. The probe showed a high
      affinity for Abeta aggregates with a Kd value of 3.5nM. It is weakly emissive by
      itself with its fluorescence quenched by electron transfer from PeT donor to the
      excited fluorophore. But selective binding to Abeta plaques would attenuate the
      PeT process and restore the fluorescence, therefore facilitating the tracking of
      Abeta plaques. The probe is advantageous in that its fluorescence is environment
      less-sensitive and no washing procedure is required to provide high contrast
      fluorescent signal when applied to stain brain tissues. As a proof of concept,
      its application has been exemplified by staining Abeta plaques in slices of brain
      tissue from double transgenic (APP/PS1) mice of Alzheimer's disease. 

PMID- 26313425
TI  - Biosorption characteristics of Uranium (VI) from aqueous solution by pollen pini.
AB  - Uranium biosorption from aqueous solutions by pollen pini (Pinus massoniana
      pollen) was studied in a bath system. The biosorbent was characterized by Fourier
      transform infrared spectroscopy and scanning electron microscope. The influences
      of pH, contact time and initial uranium concentration at room temperature were
      investigated and the experimental curves were obtained. The pollen pini exhibited
      the highest uranium sorption capacity at pH 5.0 after 2 h contact. At pH 2.5
      pollen pini also exhibited a good uranium loading capacity (>15%). Therefore
      biosorption characteristics of uranium from aqueous solution onto pollen pini
      were examined at pH 2.5 as well. The kinetics followed a pseudo-second-order rate
      equation and adsorption process was well fitted with the Freundlich isotherm at
      both pH. The adsorption of uranium by the biosorbent was confirmed by energy
      dispersive spectroscopy. The present study suggested that pollen pini could be a
      suitable biosorbent for biosorption uranium (VI) from aqueous solution in a fast,
      low cost and convenient approach. 

PMID- 26313424
TI  - Social scaffolding of human amygdala-mPFCcircuit development.
AB  - Strong evidence indicates that reciprocal connections between the amygdala and
      the medial prefrontal cortex (mPFC) support fundamental aspects of emotional
      behavior in adulthood. However, this circuitry is slow to develop in humans,
      exhibiting immaturity in childhood. The argument is made that the development of
      this circuitry in humans is intimately associated with caregiving, such that
      parental availability during childhood provides important and enduring
      scaffolding of neuroaffective processes that ultimately form of the nature of the
      adult phenotype. 

PMID- 26313426
TI  - Reconstruction of national distribution of indoor radon concentration in Russia
      using results of regional indoor radon measurement programs.
AB  - The aim of the paper is a reconstruction of the national distribution and
      estimation of the arithmetic average indoor radon concentration in Russia using
      the data of official annual 4-DOZ reports. Annual 4-DOZ reports summarize results
      of radiation measurements in 83 regions of Russian Federation. Information on
      more than 400,000 indoor radon measurements includes the average indoor radon
      isotopes equilibrium equivalent concentration (EEC) and number of measurements by
      regions and by three main types of houses: wooden, one-storey non-wooden, and
      multi-storey non-wooden houses. To reconstruct the national distribution, all
      Russian model sample was generated by integration of sub-samples created using
      the results of each annual regional program of indoor radon measurements in each
      type of buildings. According to indoor radon concentration distribution
      reconstruction, all-Russian average indoor radon concentration is 48 Bq/m(3).
      Average indoor radon concentration by region ranges from 12 to 207 Bq/m(3). The
      95-th percentile of the distribution is reached at indoor radon concentration 160
      Bq/m(3).

PMID- 26313427
TI  - Mechanisms of Oscillatory Reactions Deduced from Bifurcation Diagrams.
AB  - The classification/categorization of oscillatory chemical reactions and the
      determination of the connectivity of species in a reaction mechanism can be
      deduced from several experiments. In this article we show the same for
      bifurcation diagrams. We construct such diagrams for skeletal models of each of
      the known categories; these are distinct and can be used for the classification
      of species essential for oscillations and for the categorization of oscillatory
      reactions. The bifurcation diagrams are closely related to the concentration
      shift matrix. Prototypes of categories 1B and 1C are extended by adding
      nonessential species. By assuming that in a flow-through stirred reactor
      bifurcation diagrams for each pair of constraints (the inflow concentrations and
      the flow rate) can be measured, we are able to determine the category of the
      examined oscillator and also deduce the connectivity of the corresponding
      reaction network. Bifurcation diagrams possess a cusp region with specific tilt.
      This information together with the knowledge of a concentration shift across the
      saddle-node bifurcation provide the clues for categorization as well as for the
      reconstruction of the network's connectivity. As an example, we present an
      analysis of the Belousov-Zhabotinsky reaction represented by the Field-Koros
      Noyes mechanism and discuss the feasibility of reconstruction of the mechanism
      from experiments. 

PMID- 26313428
TI  - Ratiometric Signaling of Hypochlorite by the Oxidative Cleavage of
      Sulfonhydrazide-Based Rhodamine-Dansyl Dyad.
AB  - A reaction-based probe 1 for hypochlorite signaling was designed by the
      conjugation of two fluorophores, rhodamine and dansyl moieties, by the reaction
      of rhodamine B base with dansylhydrazine. Probe 1 exhibited pronounced
      hypochlorite-selective chromogenic and fluorescent signaling behavior over other
      oxidants used in practical applications, such as hydrogen peroxide, peracetic
      acid, and ammonium persulfate, as well as commonly encountered metal ions and
      anions. Signaling was attributed to the hypochlorite-induced oxidative cleavage
      of the sulfonhydrazide linkage of the probe. In particular, favorable ratiometric
      fluorescence signaling was possible by utilizing the emissions of the two
      fluorophores. A detection limit of 1.13 * 10(-6) M (0.058 ppm) was estimated for
      the determination of hypochlorite. A paper-based test strip was prepared and was
      used as a semiquantitative indicator for the presence of hypochlorite in aqueous
      solutions. The probe was also successfully applied for the determination of
      hypochlorite in practical tap water samples. 

PMID- 26313430
TI  - Comblike Polyethylenimine-Based Polyplexes: Balancing Toxicity, Cell
      Internalization, and Transfection Efficiency via Polymer Chain Topology.
AB  - Comblike polyethylenimines with varying degrees of polymerization of both the
      main and side chains as well as different grafting densities were evaluated as
      gene delivery vectors. They were able to condense linear and plasmid DNA into
      nanosized polyplex particles with dimensions and surface potentials in the 130
      330 nm and -30 to +15 mV ranges, respectively, depending on the amine/phosphate
      (N/P) ratio. The polyplexes remained stable in aqueous and buffer solutions from
      several hours up to several days. The moderate colloidal stability was also
      manifested in a relatively broad size distribution (PDI typically above 0.2) and
      structural polymorphism observed by transmission electron microscopy. Both the
      neat polymers and polyplexes displayed low cytotoxicity in WISH cells as the
      relative cell viability was more than 60%. Experiments with lysosomal
      fluorescence staining revealed that the internalization pathways and, in turn,
      transfection efficiency of the polyplex nanoparticles depended on the polymer
      chain topology. The vector systems based on the polymers of denser structure can
      be considered to be promising systems for gene transfection in eukaryotic cells. 

PMID- 26313429
TI  - Synthesis and Pharmacological Characterization of C4-(Thiotriazolyl)-substituted
      2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylates. Identification of
      (1R,2S,4R,5R,6R)-2-Amino-4-(1H-1,2,4-triazol-3-ylsulfanyl)bicyclo[3.1.0]hexane
      2,6-dicarboxylic Acid (LY2812223), a Highly Potent, Functionally Selective mGlu2
      Receptor Agonist.
AB  - Identification of orthosteric mGlu(2/3) receptor agonists capable of
      discriminating between individual mGlu2 and mGlu3 subtypes has been highly
      challenging owing to the glutamate-site sequence homology between these proteins.
      Herein we detail the preparation and characterization of a series of molecules
      related to (1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylate 1
      (LY354740) bearing C4-thiotriazole substituents. On the basis of second messenger
      responses in cells expressing other recombinant human mGlu2/3 subtypes, a number
      of high potency and efficacy mGlu2 receptor agonists exhibiting low potency mGlu3
      partial agonist/antagonist activity were identified. From this, (1R,2S,4R,5R,6R)
      2-amino-4-(1H-1,2,4-triazol-3-ylsulfanyl)bicyclo[3.1.0]hexane-2,6-dicarboxylic
      acid 14a (LY2812223) was further characterized. Cocrystallization of 14a with the
      amino terminal domains of hmGlu2 and hmGlu3 combined with site-directed mutation
      studies has clarified the underlying molecular basis of this unique pharmacology.
      Evaluation of 14a in a rat model responsive to mGlu2 receptor activation coupled
      with a measure of central drug disposition provides evidence that this molecule
      engages and activates central mGlu2 receptors in vivo.

PMID- 26313431
TI  - Integrating High-Dimensional Transcriptomics and Image Analysis Tools into Early
      Safety Screening: Proof of Concept for a New Early Drug Development Strategy.
AB  - During drug discovery and development, the early identification of adverse
      effects is expected to reduce costly late-stage failures of candidate drugs. As
      risk/safety assessment takes place rather late during the development process and
      due to the limited ability of animal models to predict the human situation,
      modern unbiased high-dimensional biology readouts are sought, such as molecular
      signatures predictive for in vivo response using high-throughput cell-based
      assays. In this theoretical proof of concept, we provide findings of an in-depth
      exploration of a single chemical core structure. Via transcriptional profiling,
      we identified a subset of close analogues that commonly downregulate multiple
      tubulin genes across cellular contexts, suggesting possible spindle poison
      effects. Confirmation via a qualified toxicity assay (in vitro micronucleus test)
      and the identification of a characteristic aggregate-formation phenotype via
      exploratory high-content imaging validated the initial findings. SAR analysis
      triggered the synthesis of a new set of compounds and allowed us to extend the
      series showing the genotoxic effect. We demonstrate the potential to flag
      toxicity issues by utilizing data from exploratory experiments that are typically
      generated for target evaluation purposes during early drug discovery. We share
      our thoughts on how this approach may be incorporated into drug development
      strategies. 

PMID- 26313432
TI  - Impact of late radiation effects on cancer survivor children: an integrative
      review.
AB  - We aimed to identify the late effects of radiation exposure in pediatric cancer
      survivors. An integrated literature review was performed in the databases MEDLINE
      and LILACS and SciELO. Included were articles in Portuguese and English,
      published over the past 10 years, using the following keywords:
      "neoplasias/neoplasms" AND "radioterapia/radiotherapy" AND "radiacao/radiation".
      After analysis, 14 articles - published in nine well-known journals - met the
      inclusion criteria. The publications were divided into two categories: "Late
      endocrine effects" and "Late non-endocrine effects". Considering the increased
      survival rates in children who had cancer, the impact of late effects of exposure
      to radiation during radiological examinations for diagnosis and treatment was
      analyzed. Childhood cancer survivors were exposed to several late effects and
      should be early and regularly followed up, even when exposed to low radiation
      doses. 

PMID- 26313433
TI  - Higher overall survival in metastatic pancreatic cancer: the impact of where and
      how treatment is delivered.
AB  - OBJECTIVE: To determine the overall survival of patients with advanced pancreatic
      cancer and evaluate factors that impact prognosis in a private cancer center.
      METHODS: Data from the Hospital Cancer Registry at Hospital Israelita Albert
      Einstein were retrospectively collected. The patients enrolled had metastatic
      cancer at diagnosis or earlier staging and subsequent recurrence. Cases of
      neuroendocrine tumors were excluded. RESULTS: A total of 65 patients were
      evaluated, including 63 with adenocarcinoma. The median overall survival for
      patients in all stages was 20.7 months (95%CI: 15.6-25.7), while the overall
      survival of metastatic disease was 13.3 months. Among the 33 cases with stage IV
      cancer, there was no evidence of a statistically significant association between
      median survival and CA19-9 dosage (p=0.212), tumor location (p=0.482), first
      treatment performed (p=0.337), lymphovascular invasion (p=0.286), and age
      (p=0.152). However, the number of lines of chemotherapy was significantly
      associated with survival (log-rank p=0.013), with an estimated median survival of
      10.2 months for patients who received up to two lines of treatment and 23.5
      months for those receiving more than two lines of chemotherapy. CONCLUSION: The
      survival of patients treated was longer than that reported in the literature. The
      only statistically significant factor related to increased survival was higher
      number of lines of chemotherapy received. We believe that the higher
      socioeconomic status of patients surveyed in this study, as well as their greater
      access to treatment options, may have influenced their overall survival.

PMID- 26313434
TI  - Robot-assisted needle insertion for venous catheterization.
AB  - Vein access can be challenging for a variety of patients. The development of
      robots-assisted central or peripheral veins puncture would facilitate life of
      health professionals and patients. New robots are under development for this
      purpose and probably they will become available for practical use in the near
      future. These techniques may decrease significantly the cost of medicine, which
      currently uses less informatics resources than other industries. 

PMID- 26313435
TI  - An update of neurological manifestations of vasculitides and connective tissue
      diseases: a literature review.
AB  - Vasculitides comprise a heterogeneous group of autoimmune disorders, occurring as
      primary or secondary to a broad variety of systemic infectious, malignant or
      connective tissue diseases. The latter occur more often but their pathogenic
      mechanisms have not been fully established. Frequent and varied central and
      peripheral nervous system complications occur in vasculitides and connective
      tissue diseases. In many cases, the neurological disorders have an atypical
      clinical course or even an early onset, and the healthcare professionals should
      be aware of them. The purpose of this brief review was to give an update of the
      main neurological disorders of common vasculitis and connective tissue diseases,
      aiming at accurate diagnosis and management, with an emphasis on pathophysiologic
      mechanisms. 

PMID- 26313436
TI  - Comparative analysis of survival between elderly and non-elderly severe sepsis
      and septic shock resuscitated patients.
AB  - OBJECTIVE: To compare outcomes between elderly (>=65 years old) and non-elderly
      (<65 years old) resuscitated severe sepsis and septic shock patients and
      determine predictors of death among elderly patients. METHODS: Retrospective
      cohort study including 848 severe sepsis and septic shock patients admitted to
      the intensive care unit between January 2006 and March 2012. RESULTS: Elderly
      patients accounted for 62.6% (531/848) and non-elderly patients for 37.4%
      (317/848). Elderly patients had a higher APACHE II score [22 (18-28)versus 19 (15
      24); p<0.001], compared to non-elderly patients, although the number of organ
      dysfunctions did not differ between the groups. No significant differences were
      found in 28-day and in-hospital mortality rates between elderly and non-elderly
      patients. The length of hospital stay was higher in elderly compared to non
      elderly patients admitted with severe sepsis and septic shock [18 (10-41)versus
      14 (8-29) days, respectively; p=0.0001]. Predictors of death among elderly
      patients included age, site of diagnosis, APACHE II score, need for mechanical
      ventilation and vasopressors. CONCLUSION: In this study population early
      resuscitation of elderly patients was not associated with increased in-hospital
      mortality. Prospective studies addressing the long-term impact on functional
      status and quality of life are necessary.

PMID- 26313437
TI  - Fluid therapy for septic shock resuscitation: which fluid should be used?
AB  - Early resuscitation of septic shock patients reduces the sepsis-related morbidity
      and mortality. The main goals of septic shock resuscitation include volemic
      expansion, maintenance of adequate tissue perfusion and oxygen delivery, guided
      by central venous pressure, mean arterial pressure, mixed or central venous
      oxygen saturation and arterial lactate levels. An aggressive fluid resuscitation,
      possibly in association with vasopressors, inotropes and red blood cell
      concentrate transfusion may be necessary to achieve those hemodynamic goals.
      Nonetheless, even though fluid administration is one of the most common
      interventions offered to critically ill patients, the most appropriate type of
      fluid to be used remains controversial. According to recently published clinical
      trials, crystalloid solutions seem to be the most appropriate type of fluids for
      initial resuscitation of septic shock patients. Balanced crystalloids have
      theoretical advantages over the classic solutions, but there is not enough
      evidence to indicate it as first-line treatment. Additionally, when large amounts
      of fluids are necessary to restore the hemodynamic stability, albumin solutions
      may be a safe and effective alternative. Hydroxyethyl starches solutions must be
      avoided in septic patients due to the increased risk of acute renal failure,
      increased need for renal replacement therapy and increased mortality. Our
      objective was to present a narrative review of the literature regarding the major
      types of fluids and their main drawbacks in the initial resuscitation of the
      septic shock patients. 

PMID- 26313438
TI  - How to choose the therapeutic goals to improve tissue perfusion in septic shock.
AB  - The early recognition and treatment of severe sepsis and septic shock is the key
      to a successful outcome. The longer the delay in starting treatment, the worse
      the prognosis due to persistent tissue hypoperfusion and consequent development
      and worsening of organ dysfunction. One of the main mechanisms responsible for
      the development of cellular dysfunction is tissue hypoxia. The adjustments
      necessary for adequate tissue blood flow and therefore of oxygen supply to
      metabolic demand according to the assessment of the cardiac index and oxygen
      extraction rate should be performed during resuscitation period, especially in
      high complexity patients. New technologies, easily handled at the bedside, and
      new studies that directly assess the impact of macro-hemodynamic parameter
      optimization on microcirculation and in the clinical outcome of septic patients,
      are needed. 

PMID- 26313439
TI  - Comparison of thromboprophylaxis patterns in arthroplasty in public and private
      hospitals.
AB  - OBJECTIVE: To compare therapy for prophylaxis of venous thromboembolism and costs
      related to hospitalization of patients undergoing total knee and hip replacement
      within the context of the Brazilian health system. METHODS: A retrospective study
      of patients undergoing arthroplasty in 2010 in a public hospital and two private
      hospitals in the state of Sao Paulo, conducted by means of medical record review.
      Costs were estimated based on the use of health care resources during
      hospitalization. A descriptive analysis was performed using frequency and mean
      (standard deviation) according to the type of care delivered (by public or
      private organization). RESULTS: A total of 215 patients were evaluated, and 56.3%
      were submitted to knee surgery and 43.7%, to hip replacement. Approximately 88%
      and 98% of patients from public and private health services, respectively,
      received some form of venous thromboembolism prophylaxis, and enoxaparin was the
      drug most widely used in both systems. The total cost of prophylaxis was R$
      1,873.01 (R$ 26.38 per patient) in the public service and R$ 21,559.73 (R$ 163.33
      per patient) in the private service. For the individuals who presented with
      thromboembolism, the average cost of hospitalization was R$ 6,210.80 and R$
      43,792.59 per patient in public and private health services, respectively.
      CONCLUSION: Thromboembolism prophylaxis in patients undergoing arthroplasty is
      most commonly used in the private health services than public organizations,
      despite its high costs in both services. The cost per patient with thrombosis
      during hospitalization was higher than the total cost of prophylaxis, suggesting
      that prevention is associated to better cost-benefit ratio.

PMID- 26313441
TI  - Efficient cell pairing in droplets using dual-color sorting.
AB  - The use of microfluidic droplets has become a powerful tool for the screening and
      manipulation of cells. However, currently this is restricted to assays involving
      a single cell type. Studies on the interaction of different cells (e.g. in
      immunology) as well as the screening of antibody-secreting cells in assays
      requiring an additional reporter cell, have not yet been successfully
      demonstrated. Based on Poisson statistics, the probability for the generation of
      droplets hosting exactly one cell of two different types is just 13.5%. To
      overcome this limitation, we have developed an approach in which different cell
      types are stained with different fluorescent dyes. Subsequent to encapsulation
      into droplets, the resulting emulsion is injected into a very compact sorting
      device allowing for analysis at high magnification and fixation of the cells
      close to the focal plane. By applying dual-color sorting, this furthermore
      enables the specific collection and analysis of droplets with exactly two
      different cells. Our approach shows an efficiency of up to 86.7% (more than 97%
      when also considering droplets hosting one or more cells of each type), and,
      hence, should pave the way for a variety of cell-based assays in droplets. 

PMID- 26313442
TI  - Switchable 3D liquid crystal grating generated by periodic photo-alignment on
      both substrates.
AB  - A planar liquid crystal (LC) cell is developed in which two photo-alignment
      layers have been illuminated with respectively a horizontal and a vertical
      diffraction pattern of interfering left- and right-handed circularly polarized
      light. In the bulk of the cell, a complex LC configuration is obtained with
      periodicity in two dimensions. Remarkably, the period of the structure is larger
      than the period of the interference pattern, indicating that lowering of the
      symmetry allows a reduction in the elastic energy. The liquid crystal
      configuration depends on the periodicity of the alignment but also on the
      thickness of the cell. By applying a voltage over the electrodes, the power going
      into the different diffracted orders can be tuned. Finite element (FE)
      simulations based on Q-tensor theory are used to find the 3D equilibrium director
      distribution, which is used to simulate the near-field transmission profile based
      on the Jones calculus. A 2D Fourier transform is performed for both the x- and y
      component of the transmitted wave to find the diffraction efficiency. 

PMID- 26313440
TI  - Quality of emergency rooms and urgent care services: user satisfaction.
AB  - OBJECTIVE: To evaluate the quality of emergency rooms and urgent care services
      according to the satisfaction of their users. METHODS: A cross-sectional
      descriptive study with a quantitative approach. The sample comprised 136 users
      and was drawn at random. Data collection took place between October and November
      2012 using a structured questionnaire. RESULTS: Participants were mostly male
      (64.7%) aged less than 30 years (55.8%), and the predominant level of education
      was high school (54.4%). Among the items evaluated, those that were statistically
      associated with levels of satisfaction with care were waiting time, confidence in
      the service, model of care, and the reason for seeking care related to acute
      complaints, cleanliness, and comfortable environment. CONCLUSION: Accessibility,
      hospitality, and infrastructure were considered more relevant factors for patient
      satisfaction than the cure itself.

PMID- 26313443
TI  - Downregulation of Long Noncoding RNA Meg3 Affects Insulin Synthesis and Secretion
      in Mouse Pancreatic Beta Cells.
AB  - Increasing evidence indicates that long noncoding RNAs (lncRNAs) are involved in
      diverse biological process. Mouse maternal expressed gene 3 (Meg3) is an
      imprinted gene and essential for development. Here, we explored the relationship
      between Meg3 and the function of mouse beta cells in vitro and in vivo. Real-time
      PCR analyses revealed that Meg3 was more abundantly expressed in Balb/c mouse
      islets than exocrine glands. Moreover, the expression of Meg3 in islets was
      decreased in T1DM (NOD female mice) and T2DM (db/db mice) models. Meg3 expression
      was modulated dynamically by glucose in Min6 cells and isolated mouse islets. The
      function role of Meg3 was investigated in Min6 cells and normal mouse by
      knockdown of Meg3 using small interfering RNA. After suppression of Meg3
      expression in vitro, insulin synthesis and secretion were impaired and the rate
      of beta cells apoptosis was increased. Moreover, knockdown of Meg3 in vivo led to
      the impaired glucose tolerance and decreased insulin secretion, consisted with
      the reduction of insulin positive cells areas by immunochemistry assays. Notably,
      islets from Meg3 interference groups showed significant decrease of Pdx-1 and
      MafA expression in mRNA and protein levels. These results indicate that Meg3 may
      function as a new regulator of maintaining beta cells identity via affecting
      insulin production and cell apoptosis. J. Cell. Physiol. 231: 852-862, 2016. (c)
      2015 Wiley Periodicals, Inc.

PMID- 26313445
TI  - Randomized controlled trial of the NS5A inhibitor daclatasvir plus pegylated
      interferon and ribavirin for HCV genotype-4 (COMMAND-4).
AB  - BACKGROUND: Treatment options for HCV genotype-4 (GT4) are limited. This Phase
      III study (COMMAND-4; AI444-042) evaluated the efficacy and safety of daclatasvir
      (DCV), a pan-genotypic HCV NS5A inhibitor, with pegylated interferon
      alpha2a/ribavirin (PEG-IFN/RBV) in treatment-naive patients with HCV GT4
      infection. METHODS: Patients were randomly assigned (2:1; blinded) to treatment
      with DCV 60 mg (n=82) or placebo (n=42) once daily plus PEG-IFN 180 ug weekly and
      RBV 1,000-1,200 mg/day (weight-based) twice daily. DCV-treated patients with
      undetectable HCV RNA at weeks 4 and 12 (eRVR) received 24 weeks of DCV plus PEG
      IFN/RBV; those without eRVR received an additional 24 weeks of PEG-IFN/RBV. All
      placebo-treated patients received 48 weeks of PEG-IFN/RBV. The primary end point
      was sustained virological response (SVR) at post-treatment week 12 (SVR12).
      RESULTS: Patients were 75% IL28B non-CC and 11% had cirrhosis. SVR rates (HCV RNA
      < lower limit of quantitation [LLOQ]) at post-treatment week 12 or later (imputed
      to include patients missing SVR12 assessments but had SVR after post-treatment
      week 12) were 82% (67/82) with DCV plus PEG-IFN/RBV versus 43% (18/42) with PEG
      IFN/RBV (P<0.0001). In DCV recipients, SVR12 rates were comparable across
      subgroups. The safety and tolerability profile of DCV plus PEG-IFN/RBV was
      comparable to that of PEG-IFN/RBV. Discontinuations due to adverse events
      occurred in 4.9% of patients receiving DCV plus PEG-IFN/RBV and 7.1% of patients
      receiving PEG-IFN/RBV. CONCLUSIONS: In treatment-naive patients with HCV GT4
      infection, DCV plus PEG-IFN/RBV achieved higher SVR12 rates than PEG-IFN/RBV
      alone. These data support DCV-based regimens for treatment of HCV GT4 infection,
      including all-oral combinations with other direct-acting antivirals (AI444-042;
      ClinicalTrials.gov NCT01448044).

PMID- 26313444
TI  - Neonicotinoid Insecticides and Their Impacts on Bees: A Systematic Review of
      Research Approaches and Identification of Knowledge Gaps.
AB  - It has been suggested that the widespread use of neonicotinoid insecticides
      threatens bees, but research on this topic has been surrounded by controversy. In
      order to synthesize which research approaches have been used to examine the
      effect of neonicotinoids on bees and to identify knowledge gaps, we
      systematically reviewed research on this subject that was available on the Web of
      Science and PubMed in June 2015. Most of the 216 primary research studies were
      conducted in Europe or North America (82%), involved the neonicotinoid
      imidacloprid (78%), and concerned the western honey bee Apis mellifera (75%).
      Thus, little seems to be known about neonicotinoids and bees in areas outside
      Europe and North America. Furthermore, because there is considerable variation in
      ecological traits among bee taxa, studies on honey bees are not likely to fully
      predict impacts of neonicotinoids on other species. Studies on crops were
      dominated by seed-treated maize, oilseed rape (canola) and sunflower, whereas
      less is known about potential side effects on bees from the use of other
      application methods on insect pollinated fruit and vegetable crops, or on lawns
      and ornamental plants. Laboratory approaches were most common, and we suggest
      that their capability to infer real-world consequences are improved when combined
      with information from field studies about realistic exposures to neonicotinoids.
      Studies using field approaches often examined only bee exposure to neonicotinoids
      and more field studies are needed that measure impacts of exposure. Most studies
      measured effects on individual bees. We suggest that effects on the individual
      bee should be linked to both mechanisms at the sub-individual level and also to
      the consequences for the colony and wider bee populations. As bees are
      increasingly facing multiple interacting pressures future research needs to
      clarify the role of neonicotinoids in relative to other drivers of bee declines. 

PMID- 26313446
TI  - Accuracy of Genomic Selection in a Rice Synthetic Population Developed for
      Recurrent Selection Breeding.
AB  - Genomic selection (GS) is a promising strategy for enhancing genetic gain. We
      investigated the accuracy of genomic estimated breeding values (GEBV) in four
      inter-related synthetic populations that underwent several cycles of recurrent
      selection in an upland rice-breeding program. A total of 343 S2:4 lines extracted
      from those populations were phenotyped for flowering time, plant height, grain
      yield and panicle weight, and genotyped with an average density of one marker per
      44.8 kb. The relative effect of the linkage disequilibrium (LD) and minor allele
      frequency (MAF) thresholds for selecting markers, the relative size of the
      training population (TP) and of the validation population (VP), the selected
      trait and the genomic prediction models (frequentist and Bayesian) on the
      accuracy of GEBVs was investigated in 540 cross validation experiments with 100
      replicates. The effect of kinship between the training and validation populations
      was tested in an additional set of 840 cross validation experiments with a single
      genomic prediction model. LD was high (average r2 = 0.59 at 25 kb) and decreased
      slowly, distribution of allele frequencies at individual loci was markedly skewed
      toward unbalanced frequencies (MAF average value 15.2% and median 9.6%), and
      differentiation between the four synthetic populations was low (FST <=0.06). The
      accuracy of GEBV across all cross validation experiments ranged from 0.12 to 0.54
      with an average of 0.30. Significant differences in accuracy were observed among
      the different levels of each factor investigated. Phenotypic traits had the
      biggest effect, and the size of the incidence matrix had the smallest.
      Significant first degree interaction was observed for GEBV accuracy between
      traits and all the other factors studied, and between prediction models and LD,
      MAF and composition of the TP. The potential of GS to accelerate genetic gain and
      breeding options to increase the accuracy of predictions are discussed. 

PMID- 26313447
TI  - The Long and Winding Road (Apologies to the Beatles).

PMID- 26313448
TI  - Development of Photodynamic Antimicrobial Chemotherapy (PACT) for Clostridium
      difficile.
AB  - BACKGROUND: Clostridium difficile is the leading cause of antibiotic-associated
      diarrhoea and pseudo membranous colitis in the developed world. The aim of this
      study was to explore whether Photodynamic Antimicrobial Chemotherapy (PACT) could
      be used as a novel approach to treating C. difficile infections. METHODS: PACT
      utilises the ability of light-activated photosensitisers (PS) to produce reactive
      oxygen species (ROS) such as free radical species and singlet oxygen, which are
      lethal to cells. We screened thirteen PS against C. difficile planktonic cells,
      biofilm and germinating spores in vitro, and cytotoxicity of effective compounds
      was tested on the colorectal adenocarcinoma cell-line HT-29. RESULTS: Three PS
      were able to kill 99.9% of bacteria in both aerobic and anaerobic conditions,
      both in the planktonic state and in a biofilm, after exposure to red laser light
      (0.2 J/cm2) without harming model colon cells. The applicability of PACT to
      eradicate C. difficile germinative spores indirectly was also shown, by first
      inducing germination with the bile salt taurocholate, followed by PACT.
      CONCLUSION: This innovative and simple approach offers the prospect of a new
      antimicrobial therapy using light to treat C. difficile infection of the colon.

PMID- 26313449
TI  - Beyond Contagion: Reality Mining Reveals Complex Patterns of Social Influence.
AB  - Contagion, a concept from epidemiology, has long been used to characterize social
      influence on people's behavior and affective (emotional) states. While it has
      revealed many useful insights, it is not clear whether the contagion metaphor is
      sufficient to fully characterize the complex dynamics of psychological states in
      a social context. Using wearable sensors that capture daily face-to-face
      interaction, combined with three daily experience sampling surveys, we collected
      the most comprehensive data set of personality and emotion dynamics of an entire
      community of work. From this high-resolution data about actual (rather than self
      reported) face-to-face interaction, a complex picture emerges where contagion
      (that can be seen as adaptation of behavioral responses to the behavior of other
      people) cannot fully capture the dynamics of transitory states. We found that
      social influence has two opposing effects on states: adaptation effects that go
      beyond mere contagion, and complementarity effects whereby individuals' behaviors
      tend to complement the behaviors of others. Surprisingly, these effects can
      exhibit completely different directions depending on the stable personality or
      emotional dispositions (stable traits) of target individuals. Our findings
      provide a foundation for richer models of social dynamics, and have implications
      on organizational engineering and workplace well-being. 

PMID- 26313450
TI  - Safety and efficacy of ranirestat in patients with mild-to-moderate diabetic
      sensorimotor polyneuropathy.
AB  - We examined the efficacy and safety of ranirestat in patients with diabetic
      sensorimotor polyneuropathy (DSPN). Patients (18-75 years) with stable type 1/2
      diabetes mellitus and DSPN were eligible for this global, double-blind, phase
      II/III study (ClinicalTrials.gov NCT00927914). Patients (n = 800) were randomized
      1 : 1 : 1 to placebo, ranirestat 40 mg/day or 80 mg/day (265 : 264 : 271). Change
      in peroneal motor nerve conduction velocity (PMNCV) from baseline to 24 months
      was the primary endpoint with a goal improvement vs. placebo >=1.2 m/s. Other
      endpoints included symptoms, quality-of-life, and safety. Six hundred thirty
      three patients completed the study. The PMNCV difference from placebo was
      significant at 6, 12, and 18 months in both ranirestat groups, but <1.2 m/s. The
      mean improvement from baseline at 24 months was +0.49, +0.95, and +0.90 m/s for
      placebo, ranirestat 40 mg and 80 mg, respectively (NS). The treatment difference
      vs. placebo reached significance when ranirestat groups were combined in a post
      hoc analysis (+0.44 m/s; p = 0.0237). There was no effect of ranirestat on safety
      assessments, secondary or exploratory endpoints vs. placebo. Ranirestat was well
      tolerated and improved PMNCV, but did not achieve any efficacy endpoints. The
      absence of PMNCV worsening in the placebo group underscores the challenges of
      DSPN studies in patients with well-controlled diabetes. 

PMID- 26313453
TI  - Transition-Metal-Free Cross-Coupling of Aryl and N-Heteroaryl Cyanides with
      Benzylic Zinc Reagents.
AB  - Functionalized 4-benzylated pyridines can be efficiently prepared by a transition
      metal-free cross-coupling between various benzylic zinc chlorides and substituted
      4-cyanopyridines in THF/DMPU under microwave irradiation (40  degrees C, 0.5-1.5
      h). Selective benzylations on polycyano-aromatics have also been achieved under
      these mild conditions. We also report a novel oxidative nucleophilic substitution
      of a hydrogen on 1,3-dicyanobenzene using benzylic zinc reagents. 

PMID- 26313451
TI  - Genetic Adaptation of Achromobacter sp. during Persistence in the Lungs of Cystic
      Fibrosis Patients.
AB  - Achromobacter species are increasingly isolated from the respiratory tract of
      cystic fibrosis patients and often a chronic infection is established. How
      Achromobacter sp. adapts to the human host remains uncharacterised. By comparing
      longitudinally collected isolates of Achromobacter sp. isolated from five CF
      patients, we have investigated the within-host evolution of clonal lineages. The
      majority of identified mutations were isolate-specific suggesting co-evolution of
      several subpopulations from the original infecting isolate. The largest
      proportion of mutated genes were involved in the general metabolism of the
      bacterium, but genes involved in virulence and antimicrobial resistance were also
      affected. A number of virulence genes required for initiation of acute infection
      were selected against, e.g. genes of the type I and type III secretion systems
      and genes related to pilus and flagellum formation or function. Six antimicrobial
      resistance genes or their regulatory genes were mutated, including large
      deletions affecting the repressor genes of an RND-family efflux pump and a beta
      lactamase. Convergent evolution was observed for five genes that were all
      implicated in bacterial virulence. Characterisation of genes involved in
      adaptation of Achromobacter to the human host is required for understanding the
      pathogen-host interaction and facilitate design of future therapeutic
      interventions. 

PMID- 26313452
TI  - Is Hemoglobin Level in Patients with Nasopharyngeal Carcinoma Still a Significant
      Prognostic Factor in the Era of Intensity-Modulated Radiotherapy Technology?
AB  - BACKGROUND: Hemoglobin (Hb) levels are regarded as an important determinant of
      outcome in a number of cancers treated with radiotherapy. However, for patients
      treated with intensity modulated radiotherapy (IMRT), information regarding the
      prognostic value of hemoglobin level is scarce. PATIENTS AND METHODS: A total of
      650 patients with nasopharyngeal carcinoma (NPC), enrolled between May, 2005, and
      November, 2012, were included in this study. The prognostic significance of
      hemoglobin level (anemia or no-anemia) at three different time points was
      investigated, including before treatment, during treatment and at the last week
      of treatment. Univariate and multivariate analyses were conducted using the log
      rank test and the Cox proportional hazards model, respectively. RESULTS: The 5
      year OS (overall survival) rate of patients who were anemia and no-anemia before
      treatment were 89.1%, and 80.7% (P = 0.01), respectively. The 5-year DMFS
      (distant metastasis-free survival) rate of patients who were anemia and no-anemia
      before treatment were 88.9%, and 78.2% (P = 0.01), respectively. The 5-year OS
      rate of patients who were anemia and no-anemia during treatment were 91.7% and
      83.3% (P = 0.004). According to multivariate analysis, the pre-treatment Hb level
      predicted a decreased DMFS (P = 0.007, HR = 2.555, 95% CI1.294-5.046). Besides,
      the mid-treatment Hb level predicted a decreased OS (P = 0.013, HR = 2.333, 95%
      CI1.199-4.541). CONCLUSIONS: Hemoglobin level is a useful prognostic factor in
      NPC patients receiving IMRT. It is important to control the level of hemoglobin
      both before and during chemoradiotherapy.

PMID- 26313454
TI  - Onset and durability of pain relief in knee osteoarthritis: Pooled results from
      two placebo trials of naproxen/esomeprazole combination and celecoxib.
AB  - OBJECTIVE: To further characterize time-to-first pain relief, effect size,
      correlations between various outcome measures and durability of relief for single
      tablet naproxen 500 mg/esomeprazole 20 mg (NAP/ESO) given twice daily and
      celecoxib (CEL) (200 mg) given once daily versus placebo in knee osteoarthritis
      (OA). METHODS: Unpublished data from two double-blind, double-dummy, placebo
      controlled trials in which patients aged >= 50 years with knee OA were randomized
      to NAP/ESO (n = 487), CEL (n = 486) or placebo (n = 246) were pooled (NCT00664560
      and NCT00665431). Acute response endpoints: 1) Time to first significant pain
      response, 2) Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain
      subscale and 3) American Pain Society Patient Outcome Questionnaire (APS-POQ)
      scores. Sustainability endpoints: 1) Routine Assessment of Patient Index Data
      (RAPID3) and 2) WOMAC Stiffness, Pain and Total scores; and Patient Global
      Assessment (PGA) at 6 and 12 weeks. Effect sizes for all measures were
      calculated. Rescue pain medication use also was analyzed, as was the correlation
      of WOMAC to RAPID3. RESULTS: NAP/ESO produced statistically significant decreases
      in WOMAC Pain on Days 2-7 and at Weeks 6 and 12 (all p < 0.05); most APS-POQ pain
      assessments with NAP/ESO were significantly improved on Days 2-7 compared with
      placebo (all p < 0.05). A good or excellent response occurred in a median of 6
      days. RAPID3 and WOMAC total/stiffness/function/PGA scores decreased
      significantly at Weeks 6 and 12 (all p < 0.05). Placebo-adjusted WOMAC pain
      effect sizes were 0.44, 0.34 and 0.25 at Day 7, week 6 and week 12, respectively.
      RAPID3 to WOMAC total and WOMAC pain to RAPID3: Pain scores were highly
      correlated at 6 and 12 weeks (correlation coefficients >0.80). No significant
      differences in overall responses were found between CEL and NAP/ESO. CONCLUSION:
      Naproxen/esomeprazole produced a significant absolute moderate early pain
      response, which was maintained for 12 weeks. RAPID3 was found to be highly
      correlated with the typical OA measure (WOMAC) and might be a useful clinical
      tool for measuring NSAID response. NCT00664560:
      https://clinicaltrials.gov/ct2/show/NCT00664560, NCT00665431:
      https://www.clinicaltrials.gov/ct2/show/NCT00665431.

PMID- 26313455
TI  - Diagnostic performance of 3D standing CT imaging for detection of knee
      osteoarthritis features.
AB  - OBJECTIVE: To determine the diagnostic performance of standing computerized
      tomography (SCT) of the knee for osteophytes and subchondral cysts compared with
      fixed-flexion radiography, using MRI as the reference standard. METHODS: Twenty
      participants were recruited from the Multicenter Osteoarthritis Study.
      Participants' knees were imaged with SCT while standing in a knee-positioning
      frame, and with postero-anterior fixed-flexion radiography and 1T MRI. Medial and
      lateral marginal osteophytes and subchondral cysts were scored on bilateral
      radiographs and coronal SCT images using the OARSI grading system and on coronal
      MRI using Whole Organ MRI Scoring. Imaging modalities were read separately with
      images in random order. Sensitivity, specificity and accuracy for the detection
      of lesions were calculated and differences between modalities were tested using
      McNemar's test. RESULTS: Participants' mean age was 66.8 years, body mass index
      was 29.6 kg/m(2) and 50% were women. Of the 160 surfaces (medial and lateral
      femur and tibia for 40 knees), MRI revealed 84 osteophytes and 10 subchondral
      cysts. In comparison with osteophytes and subchondral cysts detected by MRI, SCT
      was significantly more sensitive (93 and 100%; p < 0.004) and accurate (95 and
      99%; p < 0.001 for osteophytes) than plain radiographs (sensitivity 60 and 10%
      and accuracy 79 and 94%, respectively). For osteophytes, differences in
      sensitivity and accuracy were greatest at the medial femur (p = 0.002).
      CONCLUSIONS: In comparison with MRI, SCT imaging was more sensitive and accurate
      for detection of osteophytes and subchondral cysts than conventional fixed
      flexion radiography. Additional study is warranted to assess diagnostic
      performance of SCT measures of joint space width, progression of OA features and
      the patellofemoral joint.

PMID- 26313456
TI  - Tablet- or iPAD-based marking of OSCEs and MMIs: An imaginative cost-saving
      approach.

PMID- 26313457
TI  - Examination of the dynamic assembly equilibrium for E. coli ClpB.
AB  - Escherichia coli ClpB is a heat shock protein that belongs to the AAA+ protein
      superfamily. Studies have shown that ClpB and its homologue in yeast, Hsp104, can
      disrupt protein aggregates in vivo. It is thought that ClpB requires binding of
      nucleoside triphosphate to assemble into hexameric rings with protein binding
      activity. In addition, it is widely assumed that ClpB is uniformly hexameric in
      the presence of nucleotides. Here we report, in the absence of nucleotide, that
      increasing ClpB concentration leads to ClpB hexamer formation, decreasing NaCl
      concentration stabilizes ClpB hexamers, and the ClpB assembly reaction is best
      described by a monomer, dimer, tetramer, hexamer equilibrium under the three salt
      concentrations examined. Further, we found that ClpB oligomers exhibit relatively
      fast dissociation on the time scale of sedimentation. We anticipate our studies
      on ClpB assembly to be a starting point to understand how ClpB assembly is linked
      to the binding and disaggregation of denatured proteins.

PMID- 26313459
TI  - Hepatitis C Virus Driven AXL Expression Suppresses the Hepatic Type I Interferon
      Response.
AB  - Treatment of chronic hepatitis C virus (HCV) infection is evolving rapidly with
      the development of novel direct acting antivirals (DAAs), however viral clearance
      remains intimately linked to the hepatic innate immune system. Patients
      demonstrating a high baseline activation of interferon stimulated genes (ISGs),
      termed interferon refractoriness, are less likely to mount a strong antiviral
      response and achieve viral clearance when placed on treatment. As a result,
      suppressor of cytokine signalling (SOCS) 3 and other regulators of the IFN
      response have been identified as key candidates for the IFN refractory phenotype
      due to their regulatory role on the IFN response. AXL is a receptor tyrosine
      kinase that has been identified as a key regulator of interferon (IFN) signalling
      in myeloid cells of the immune system, but has not been examined in the context
      of chronic HCV infection. Here, we show that AXL is up-regulated following HCV
      infection, both in vitro and in vivo and is likely induced by type I/III IFNs and
      inflammatory signalling pathways. AXL inhibited type IFNalpha mediated ISG
      expression resulting in a decrease in its antiviral efficacy against HCV in
      vitro. Furthermore, patients possessing the favourable IFNL3 rs12979860 genotype
      associated with treatment response, showed lower AXL expression in the liver and
      a stronger induction of AXL in the blood, following their first dose of IFN.
      Together, these data suggest that elevated AXL expression in the liver may
      mediate an IFN-refractory phenotype characteristic of patients possessing the
      unfavourable rs12979860 genotype, which is associated with lower rates of viral
      clearance. 

PMID- 26313460
TI  - Immunogenicity and Serological Cross-Reactivity of Saliva Proteins among
      Different Tsetse Species.
AB  - Tsetse are vectors of pathogenic trypanosomes, agents of human and animal
      trypanosomiasis in Africa. Components of tsetse saliva (sialome) are introduced
      into the mammalian host bite site during the blood feeding process and are
      important for tsetse's ability to feed efficiently, but can also influence
      disease transmission and serve as biomarkers for host exposure. We compared the
      sialome components from four tsetse species in two subgenera: subgenus Morsitans:
      Glossina morsitans morsitans (Gmm) and Glossina pallidipes (Gpd), and subgenus
      Palpalis: Glossina palpalis gambiensis (Gpg) and Glossina fuscipes fuscipes
      (Gff), and evaluated their immunogenicity and serological cross reactivity by an
      immunoblot approach utilizing antibodies from experimental mice challenged with
      uninfected flies. The protein and immune profiles of sialome components varied
      with fly species in the same subgenus displaying greater similarity and cross
      reactivity. Sera obtained from cattle from disease endemic areas of Africa
      displayed an immunogenicity profile reflective of tsetse species distribution. We
      analyzed the sialome fractions of Gmm by LC-MS/MS, and identified TAg5,
      Tsal1/Tsal2, and Sgp3 as major immunogenic proteins, and the 5'-nucleotidase
      family as well as four members of the Adenosine Deaminase Growth Factor (ADGF)
      family as the major non-immunogenic proteins. Within the ADGF family, we
      identified four closely related proteins (TSGF-1, TSGF-2, ADGF-3 and ADGF-4), all
      of which are expressed in tsetse salivary glands. We describe the tsetse species
      specific expression profiles and genomic localization of these proteins. Using a
      passive-immunity approach, we evaluated the effects of rec-TSGF (TSGF-1 and TSGF
      2) polyclonal antibodies on tsetse fitness parameters. Limited exposure of tsetse
      to mice with circulating anti-TSGF antibodies resulted in a slight detriment to
      their blood feeding ability as reflected by compromised digestion, lower weight
      gain and less total lipid reserves although these results were not statistically
      significant. Long-term exposure studies of tsetse flies to antibodies
      corresponding to the ADGF family of proteins are warranted to evaluate the role
      of this conserved family in fly biology. 

PMID- 26313461
TI  - A Prognostic Analysis of Male Breast Cancer (MBC) Compared with Post-Menopausal
      Female Breast Cancer (FBC).
AB  - BACKGROUND: Male breast cancer (MBC) is known to be rare compared with female
      breast cancer (FBC) and to account for only 1% of all breast cancers. To date,
      male patients diagnosed with breast cancer are normally treated based on the
      guidelines for FBC. Specifically, studies have found that diagnosing and treating
      MBC patients under the guidelines for the treatment of post-menopausal FBC are
      more favorable than are those of pre/peri-menopausal FBC from a physiological
      perspective because MBC and post-menopausal FBC patients show high estrogen
      receptor (ER) expression in the tumor and low estrogen expression in the body. In
      this medical study, we aimed to examine whether MBC actually has the same
      prognosis as post-menopausal FBC. METHOD: We identified MBC patients who were
      diagnosed as operable and who completed clinical treatment and we used follow-up
      data that were collected from January 2001 to January 2011. Each MBC patient was
      paired with four FBC patients who were diagnosed within the same period (two were
      pre/peri-menopausal, and two were post-menopausal). We compared disease-free
      survival (DFS) and overall survival (OS) among three groups, i.e., pre/peri
      menopausal FBC (group A), post-menopausal FBC (group B) and MBC (group M), using
      the Kaplan-Meier method and a Cox proportional hazards regression model. We also
      evaluated the clinical characteristics of breast cancer patients using t-tests
      and chi-square tests. We used ten consecutive years of data that were collected
      at Zhejiang Provincial Cancer Hospital. RESULTS: We identified 91 MBC cases for
      group M, 182 FBC cases for group A and 182 FBC cases for group B. The median
      follow-up period was 112 months. MBC cases were much more frequently ER positive
      than those of group A and group B (p<0.01); a similar trend was also found for
      progesterone (PR)-positive cases (p<0.01). The MBC group showed much lower human
      epidermal growth factor receptor-2 (HER2) expression than did the other groups
      (p<0.01). The 10-year OS rates were 79.1% for group M (72/91), 79.1% (144/182)
      for group A, and 87.9% (160/182) for group B, log-rank test indicated that group
      M had similar mean OS time as group A and group B (GourpM vs group A: p = 0.709;
      group M vs group B: p = 0.042). The Cox proportional hazards regression model
      indicated that pre/peri-menopausal FBC had similar DFS (hazard ratio (HR) =
      0.706, p = 0.262) and OS (HR = 1.029, p = 0.941) values compared with MBC,
      whereas post-menopausal FBC had higher DFS (HR = 0.454, p = 0.004) and OS (HR =
      0.353, p = 0.003) values than did MBC. CONCLUSION: Based on this study, we can
      conclude that MBC displayed higher ER- and PR-positive expression and lower HER2
      positive expression than both post-menopausal and pre/peri-menopausal FBC.
      However, the DFS and OS values of MBC were similar to those of pre/peri
      menopausal FBC and were worse than were those of post-menopausal FBC.

PMID- 26313462
TI  - Risk of Critical Illness Among Patients With Solid Cancers: A Population-Based
      Observational Study.
AB  - IMPORTANCE: Critical illness may be a potential determinant of cancer outcomes
      and geographic variations, but its role has not been described before. OBJECTIVE:
      To determine the incidence of admission to intensive care units (ICUs) within 2
      years following cancer diagnosis. DESIGN, SETTING, AND PARTICIPANTS: This was a
      retrospective observational study using cancer registry data in 4 datasets from
      2000 to 2009 with linked ICU admission data from 2000 to 2011, in the West of
      Scotland region of the United Kingdom (population, 2.4 million; all 16 ICUs
      within the region). All 118,541 patients (>=16 years) diagnosed as having solid
      (nonhematological) cancers. Their median age was 69 years, and 52.0% were women.
      MAIN OUTCOMES AND MEASURES: Demographic and clinical variables associated with
      admission to an ICU and death in an ICU. RESULTS: A total of 118,541 patients met
      the study criteria. Overall, 6116 patients (5.2% [95% CI, 5.0%-5.3%]) developed a
      critical illness and were admitted to an ICU within 2 years. Risk of critical
      illness was highest at ages 60 to 69 years and higher in men. The cumulative
      incidence of critical illness was greatest for small intestinal (17.2% [95% CI,
      13.3%-21.8%]) and colorectal cancers (16.5% [95% CI, 15.9%-17.1%]). The risk
      following breast cancer was low (0.8% [95% CI, 0.7%-1.0%]). The percentage who
      died in ICUs was 14.1% (95% CI, 13.3%-15.0%), and during the hospital stay, 24.6%
      (95% CI, 23.5%-25.7%). Mortality was greatest among emergency medical admissions
      and lowest among elective surgical patients. The risk of critical illness did not
      vary by socioeconomic circumstances, but mortality was higher among patients from
      deprived areas. CONCLUSIONS AND RELEVANCE: In this study, about 1 in 20 patients
      experienced a critical illness resulting in ICU admission within 2 years of
      cancer diagnosis. The associated high mortality rate may make a significant
      contribution to overall cancer outcomes.

PMID- 26313463
TI  - Quality control of lymph node dissection in the Dutch Gastric Cancer Trial.
AB  - BACKGROUND: Current guidelines indicate that D2 resection is the standard of care
      for patients with locally advanced gastric cancer. To assess the impact of
      quality assurance of lymph node removal, non-compliance and contamination in the
      D1 and D2 study arms of the Dutch Gastric Cancer Trial were investigated with
      respect to recurrence and survival. METHODS: The location and numbers of lymph
      nodes detected at pathological investigation in the Dutch Gastric Cancer Trial
      were compared according to the guidelines of the Japanese Research Society for
      the study of Gastric Cancer. Non-compliance was defined as inadequate removal of
      lymph node stations. Contamination was defined as lymph nodes removed outside the
      intended level of resection. The dissection groups D1 and D2 were divided into
      non-compliance, compliance and contamination categories. Long-term overall
      survival was calculated for minor (2 or fewer lymph nodes) and major (more than 2
      lymph nodes) non-compliance and contamination in the D1 and D2 group, using
      Kaplan-Meier plots. RESULTS: Some 1078 patients were included, of whom 711 with
      potentially curative surgical resections were evaluated. Overall non-compliance
      was 80.5 per cent in the D1 and 81.6 per cent in the D2 group. Major non
      compliance occurred in 15.3 per cent of the D1 and 26.0 per cent of the D2 group.
      Major contamination hardly occurred. Overall 15-year survival rates in the
      randomized groups were 21.2 per cent (D1) and 29.0 per cent (D2) (P = 0.351).
      After exclusion of patients with major non-compliance and/or major contamination,
      survival rates were 23.2 per cent (319 patients) and 32.6 per cent (245)
      respectively (P = 0.261). Where there was major non-compliance, survival rates in
      the D1 (58 patients) and D2 (86) groups were 10 and 17 per cent respectively (P =
      0.302). Survival in the D2 compliant + contaminated group (139 patients) was
      significantly better than that in the D1 group without contamination (282): 35.7
      versus 19.9 per cent (P = 0.041). In the D2 group, there was a significant
      difference in survival between contaminated (95 patients) and non-contaminated
      (236) groups: 39 versus 25.1 per cent (P = 0.041). CONCLUSION: Non-compliance in
      the D2 dissection group may have obscured a significant difference in survival
      between the randomized groups. A D2 dissection with contamination was associated
      with the best survival, suggesting that extended D2 lymph node dissections
      improve survival.

PMID- 26313464
TI  - Direct gem-difluoromethylenation of sp(3)-hybridized carbon center through copper
      mediated radical/radical cross-coupling for the construction of a CH2-CF2
      linkage.
AB  - Efficient direct gem-difluoromethylenation of an sp(3)-hybridized carbon center
      in benzyl bromides using benzo-1,3-azolic (oxa-, thia- or aza-) difluoromethyl
      bromides for construction of a CH2-CF2 linkage has been developed through
      radical/radical C-C cross-coupling via two separate single electron transfer
      processes (SET) under the promotion of different copper sources. 

PMID- 26313465
TI  - Scavenger Receptor Class B Type I Regulates Plasma Apolipoprotein E Levels and
      Dietary Lipid Deposition to the Liver.
AB  - Scavenger receptor class B type I (SR-BI) is primarily responsible for the
      selective uptake of cholesteryl esters (CE) of high-density lipoprotein (HDL) by
      the liver and other tissues. In the present study, we show that SR-BI-deficient
      (scarb1(-/-)) mice are resistant to diet-induced obesity, hepatic lipid
      deposition, and glucose intolerance after 24 weeks of being fed a western-type
      diet. No differences in energy expenditure or mitochondrial function could
      account for the observed phenotype. Kinetic and gene expression analyses
      suggested reduced de novo fatty acid synthesis in scarb1(-/-) mice. Furthermore,
      adenosine monophosphate-activated protein kinase (AMPK)-stimulated hepatic FFA
      catabolism was reduced in these mice, leaving direct dietary lipid uptake from
      plasma as the major modulator of hepatic lipid content. Analysis of the
      apolipoprotein composition of plasma lipoproteins revealed a significant
      accumulation of apolipoprotein E (ApoE)-containing HDL and TG-rich lipoproteins
      in scarb1(-/-) mice that correlated with reduced plasma LpL activity. Our data
      suggest that scarb1(-/-) mice fed a western-type diet for 24 weeks accumulate CE-
      and ApoE-rich HDL of abnormal density and size. The elevated HDL-ApoE levels
      inhibit plasma LpL activity, blocking the clearance of triglyceride-rich
      lipoproteins and preventing the shuttling of dietary lipids to the liver. 

PMID- 26313466
TI  - Dissecting the role of epidermal growth factor receptor catalytic activity during
      liver regeneration and hepatocarcinogenesis.
AB  - Different data support a role for the epidermal growth factor receptor (EGFR)
      pathway during liver regeneration and hepatocarcinogenesis. However, important
      issues, such as the precise mechanisms mediating its actions and the unique
      versus redundant functions, have not been fully defined. Here, we present a novel
      transgenic mouse model expressing a hepatocyte-specific truncated form of human
      EGFR, which acts as negative dominant mutant (DeltaEGFR) and allows definition of
      its tyrosine kinase-dependent functions. Results indicate a critical role for
      EGFR catalytic activity during the early stages of liver regeneration. Thus,
      after two-thirds partial hepatectomy, DeltaEGFR livers displayed lower and
      delayed proliferation and lower activation of proliferative signals, which
      correlated with overactivation of the transforming growth factor-beta pathway.
      Altered regenerative response was associated with amplification of cytostatic
      effects of transforming growth factor-beta through induction of cell cycle
      negative regulators. Interestingly, lipid synthesis was severely inhibited in
      DeltaEGFR livers after partial hepatectomy, revealing a new function for EGFR
      kinase activity as a lipid metabolism regulator in regenerating hepatocytes. In
      spite of these profound alterations, DeltaEGFR livers were able to recover liver
      mass by overactivating compensatory signals, such as c-Met. Our results also
      indicate that EGFR catalytic activity is critical in the early preneoplastic
      stages of the liver because DeltaEGFR mice showed a delay in the appearance of
      diethyl-nitrosamine-induced tumors, which correlated with decreased proliferation
      and delay in the diethyl-nitrosamine-induced inflammatory process. CONCLUSION:
      These studies demonstrate that EGFR catalytic activity is critical during the
      initial phases of both liver regeneration and carcinogenesis and provide key
      mechanistic insights into how this kinase acts to regulate liver pathophysiology.
      (Hepatology 2016;63:604-619).

PMID- 26313467
TI  - Highly oxygenated triterpenoids from the roots of Schisandra chinensis and their
      anti-inflammatory activities.
AB  - A new highly oxygenated triterpenoid, schinchinenlactone D (1), and three known
      compounds (2-4) were isolated from the roots of Schisandra chinensis. Their
      structures were determined by combining the spectroscopic analysis with the
      theoretical computations. The anti-inflammatory activities of compounds 1-4 were
      evaluated, and compound 3 exhibits the most significant activity in the
      inhibition of NO production with an IC50 value of 10.6 MUM. 

PMID- 26313468
TI  - Growth and reproductive effects from dietary exposure to Aroclor 1268 in mink
      (Neovison vison), a surrogate model for marine mammals.
AB  - Polychlorinated biphenyls (PCBs) from the commercial mixture Aroclor 1268 were
      historically released into the Turtle-Brunswick River estuary (southeastern
      Georgia, USA) from industrial operations. Sum PCBs (SigmaPCBs) in blubber samples
      from Turtle-Brunswick River estuary bottlenose dolphins (Tursiops truncatus) have
      been reported at concentrations more than 10-fold higher than those observed in
      dolphins from adjacent regional estuaries. Given that toxicity data specific to
      Aroclor 1268 and applicable to marine mammals are limited, predicting the toxic
      effects of Aroclor 1268 in dolphins is uncertain, particularly because of its
      unique congener profile and associated physiochemical characteristics compared
      with other PCB mixtures. American mink (Neovison vison) were chosen as a
      surrogate model for cetaceans to develop marine mammalian PCB toxicity
      benchmarks. Mink are a suitable surrogate species for cetaceans in toxicity
      studies because of similarities in diet and taxonomic class, and a characteristic
      sensitivity to PCBs provides a potential safety factor when using mink toxicology
      data for cross-species extrapolations. Effects of dietary exposure to Aroclor
      1268 on reproduction, growth, and mortality in mink were compared with both a
      negative control and a positive control (3,3',4,4',5-pentachlorobiphenyl, PCB
      126). Aroclor 1268 dietary SigmaPCB concentrations ranged from 1.8 ug/g feed wet
      weight to 29 ug/g feed wet weight. Whelp success was unaffected by Aroclor 1268
      exposure at any level. Treatment mean litter size, kit growth, and kit survival
      were adversely affected relative to the negative control at dietary SigmaPCB
      concentrations of 10.6 ug/g feed wet weight and greater.

PMID- 26313469
TI  - Nanocomposite of Fe2 O3 @C@MnO2 as an Efficient Cathode Catalyst for Rechargeable
      Lithium-Oxygen Batteries.
AB  - A new design and synthesis of Fe2O3 @C@MnO2 nanocomposite via aerosol spray
      pyrolysis and electrodeposition is reported for application in rechargeable Li-O2
      batteries. Owing to the superior oxygen reduction/evolution reaction bifunctional
      catalytic activities attributed to the combined function of Fe2O3 and MnO2 and
      facile charge transfer in the carbon matrix, the nanocomposite exhibits long
      life, large capacity, and a small overpotential in Li-O2 batteries.

PMID- 26313470
TI  - National, State, and Selected Local Area Vaccination Coverage Among Children Aged
      19-35 Months - United States, 2014.
AB  - The reduction in morbidity and mortality associated with vaccine-preventable
      diseases in the United States has been described as one of the 10 greatest public
      health achievements of the first decade of the 21st century. A recent analysis
      concluded that routine childhood vaccination will prevent 322 million cases of
      disease and about 732,000 early deaths among children born during 1994-2013, for
      a net societal cost savings of $1.38 trillion. The National Immunization Survey
      (NIS) has monitored vaccination coverage among U.S. children aged 19-35 months
      since 1994. This report presents national, regional, state, and selected local
      area vaccination coverage estimates for children born from January 2011 through
      May 2013, based on data from the 2014 NIS. For most vaccinations, there was no
      significant change in coverage between 2013 and 2014. The exception was hepatitis
      A vaccine (HepA), for which increases were observed in coverage with both >=1 and
      >=2 doses. As in previous years, <1% of children received no vaccinations.
      National coverage estimates indicate that the Healthy People 2020 target* of 90%
      was met for >=3 doses of poliovirus vaccine (93.3%), >=1 dose of measles, mumps,
      and rubella vaccine (MMR) (91.5%), >=3 doses of hepatitis B vaccine (HepB)
      (91.6%), and >=1 dose of varicella vaccine (91.0%). Coverage was below target for
      >=4 doses of diphtheria, tetanus, and acellular pertussis vaccine (DTaP), the
      full series of Haemophilus influenzae type b (Hib) vaccine, hepatitis B (HepB)
      birth dose,? >=4 doses pneumococcal conjugate vaccine (PCV), >=2 doses of HepA,
      the full series of rotavirus vaccine, and the combined vaccine series.S
      Examination of coverage by child's race/ethnicity revealed lower estimated
      coverage among non-Hispanic black children compared with non-Hispanic white
      children for several vaccinations, including DTaP, the full series of Hib, PCV,
      rotavirus vaccine, and the combined series. Children from households classified
      as below the federal poverty level had lower estimated coverage for almost all of
      the vaccinations assessed, compared with children living at or above the poverty
      level. Significant variation in coverage by state  was observed for several
      vaccinations, including HepB birth dose, HepA, and rotavirus. High vaccination
      coverage must be maintained across geographic and sociodemographic groups if
      progress in reducing the impact of vaccine-preventable diseases is to be
      sustained. 

PMID- 26313471
TI  - Vaccination Coverage Among Children in Kindergarten - United States, 2014-15
      School Year.
AB  - State and local jurisdictions require children to be vaccinated before starting
      school to maintain high vaccination coverage and protect schoolchildren from
      vaccine-preventable diseases. State vaccination requirements, which include
      school vaccination and exemption laws and health department regulations, permit
      medical exemptions for students with a medical contraindication to receiving a
      vaccine or vaccine component and may allow nonmedical exemptions for religious
      reasons or philosophic beliefs. To monitor state and national vaccination
      coverage and exemption levels among children attending kindergarten, CDC analyzes
      school vaccination data collected by federally funded state, local, and
      territorial immunization programs. This report describes vaccination coverage
      estimates in 49 states and the District of Columbia (DC) and vaccination
      exemption estimates in 46 states and DC that reported the number of children with
      at least one exemption among kindergartners during the 2014-15 school year.
      Median vaccination coverage* was 94.0% for 2 doses of measles, mumps, and rubella
      (MMR) vaccine; 94.2% for the local requirements for diphtheria, tetanus, and
      acellular pertussis vaccine (DTaP); and 93.6% for 2 doses of varicella vaccine
      among the 39 states and DC with a 2-dose requirement. The median percentage of
      any exemptions? was 1.7%. Although statewide vaccination coverage among
      kindergartners was high during the 2014-15 school year, geographic pockets of low
      vaccination coverage and high exemption levels can place children at risk for
      vaccine-preventable diseases. Appropriate school vaccination coverage assessments
      can help immunization programs identify clusters of low coverage and develop
      partnerships with schools and communities to ensure that children are protected
      from vaccine-preventable diseases. 

PMID- 26313472
TI  - School-Level Practices to Increase Availability of Fruits, Vegetables, and Whole
      Grains, and Reduce Sodium in School Meals - United States, 2000, 2006, and 2014.
AB  - Students consume up to half of their daily calories at school, often through the
      federal school meal programs (e.g., National School Lunch Program) administered
      by the U.S. Department of Agriculture (USDA). In 2012, USDA published new
      required nutrition standards for school meals.* These standards were the first
      major revision to the school meal programs in >15 years and reflect current
      national dietary guidance and Institute of Medicine recommendations to meet
      students' nutrition needs. The standards require serving more fruits, vegetables,
      and whole grains and gradually reducing sodium content over 10 years. To examine
      the prevalence of school-level practices related to implementation of the
      nutrition standards, CDC analyzed data from the 2000, 2006, and 2014 School
      Health Policies and Practices Study (SHPPS) on school nutrition services
      practices related to fruits, vegetables, whole grains, and sodium. Almost all
      schools offered whole grain foods each day for breakfast and lunch, and most
      offered two or more vegetables and two or more fruits each day for lunch. The
      percentage of schools implementing practices to increase availability of fruits
      and vegetables and decrease sodium content in school meals increased from 2000
      2014. However, opportunities exist to increase the percentage of schools
      nationwide implementing these practices. 

PMID- 26313473
TI  - Injuries from Methamphetamine-Related Chemical Incidents - Five States, 2001
      2012.
AB  - Methamphetamine (meth), a highly addictive drug, can be illegally manufactured
      using easily acquired chemicals; meth production can cause fires, explosions,
      injuries, and environmental contamination. To analyze injury incidence and
      trends, data on 1,325 meth-related chemical incidents reported to the Agency for
      Toxic Substances and Disease Registry's (ATSDR) Hazardous Substances Emergency
      Events Surveillance (HSEES) system and National Toxic Substance Incidents Program
      (NTSIP) by the five participating states (Louisiana, Oregon, Utah, New York, and
      Wisconsin) with complete information during 2001-2012 were examined. The findings
      suggested that meth-related chemical incidents increased with the drug's
      popularity (2001-2004), declined with legislation limiting access to precursor
      chemicals (2005-2007), and increased again as drug makers circumvented precursor
      restrictions (2008-2012). Seven percent of meth-related chemical incidents
      resulted in injuries to 162 persons, mostly members of the general public (97
      persons, including 26 children) and law enforcement officials (42). Recent trends
      suggest a need for efforts to protect the general public, particularly children
      and law enforcement officials. Because individual state legislative actions can
      result in increased illegal meth production in neighboring states, a regional
      approach to prevention is recommended. 

PMID- 26313474
TI  - World Health Organization Guidelines for Containment of Poliovirus Following Type
      Specific Polio Eradication - Worldwide, 2015.
AB  - In 1988, the World Health Assembly of the World Health Organization (WHO)
      resolved to eradicate polio worldwide. Among the three wild poliovirus (WPV)
      types (type 1, type 2, and type 3), WPV type 2 (WPV2) has been eliminated in the
      wild since 1999, and WPV type 3 (WPV3) has not been reported since 2012. In 2015,
      only Afghanistan and Pakistan have reported WPV transmission. On May 25, 2015,
      all WHO Member States endorsed World Health Assembly resolution 68.3 on full
      implementation of the Polio Eradication and Endgame Strategic Plan 2013-2018 (the
      Endgame Plan), and with it, the third Global Action Plan to minimize poliovirus
      facility-associated risk (GAPIII). All WHO Member States have committed to
      implementing appropriate containment of WPV2 in essential laboratory and vaccine
      production facilities* by the end of 2015 and of type 2 oral poliovirus vaccine
      (OPV2) within 3 months of global withdrawal of OPV2, which is planned for April
      2016. This report summarizes critical steps for essential laboratory and vaccine
      production facilities that intend to retain materials confirmed to contain or
      potentially containing type-specific WPV, vaccine-derived poliovirus (VDPV), or
      OPV/Sabin viruses, and steps for nonessential facilities? that process specimens
      that contain or might contain polioviruses. National authorities will need to
      certify that the essential facilities they host meet the containment requirements
      described in GAPIII. After certification of WPV eradication, the use of all OPV
      will cease; final containment of all polioviruses after polio eradication and OPV
      cessation will minimize the risk for reintroduction of poliovirus into a polio
      free world. 

PMID- 26313476
TI  - Snowstorm-Related Mortality - Erie County, New York, November 2014.
AB  - During November 18-21, 2014, a narrow band of central and southern Erie County in
      New York received unprecedented amounts of snowfall. The duration of the storm
      and amount of snowfall rapidly exceeded weather service forecasts, with some
      areas receiving 60-84 inches (1.5-2.1 meters) of snow. The rapid accumulation
      resulted in stranded drivers, travel bans, and logistical challenges associated
      with snow removal. Sporadic power outages affected a limited number of
      households. Eleven deaths were linked to the snowstorm, including one that was
      directly related, nine that were indirectly related, and one that was classified
      as possibly storm-related. 

PMID- 26313475
TI  - Human Plague - United States, 2015.
AB  - Since April 1, 2015, a total of 11 cases of human plague have been reported in
      residents of six states: Arizona (two), California (one), Colorado (four),
      Georgia (one), New Mexico (two), and Oregon (one). The two cases in Georgia and
      California residents have been linked to exposures at or near Yosemite National
      Park in the southern Sierra Nevada Mountains of California. Nine of the 11
      patients were male; median age was 52 years (range = 14-79 years). Three patients
      aged 16, 52, and 79 years died. 

PMID- 26313477
TI  - Increase in Reports of Strongyloides Infection - Los Angeles County, 2013-2014.
AB  - During the 1990s, reports of infection with the nematode (roundworm)
      Strongyloides stercoralis submitted to the Los Angeles County Department of
      Public Health (LACDPH) ranged from 40 to 50 per year, but by 2000, reports had
      decreased to five per year; in 2006, Strongyloides infection was removed from the
      LACDPH reportable disease list. Currently, it is only reported at the discretion
      of Los Angeles County clinicians and laboratories as an unusual disease
      occurrence. LACDPH currently only monitors case counts and does not investigate
      reported Strongyloides cases. During 2013-2014, an increase in Strongyloides
      cases occurred, with 43 cases reported. 

PMID- 26313478
TI  - One-step (18)F labeling of biomolecules using organotrifluoroborates.
AB  - Herein we present a general protocol for the functionalization of biomolecules
      with an organotrifluoroborate moiety so that they can be radiolabeled with
      aqueous (18)F fluoride ((18)F(-)) and used for positron emission tomography (PET)
      imaging. Among the beta(+)-emitting radionuclides, fluorine-18 ((18)F) is the
      isotope of choice for PET, and it is produced, on-demand, in many hospitals
      worldwide. Organotrifluoroborates can be (18)F-labeled in one step in aqueous
      conditions via (18)F-(19)F isotope exchange. This protocol features a recently
      designed ammoniomethyltrifluoroborate, and it describes the following: (i) a
      synthetic strategy that affords modular synthesis of radiolabeling precursors via
      a copper-catalyzed 'click' reaction; and (ii) a one-step (18)F-labeling method
      that obviates the need for HPLC purification. Within 30 min, (18)F-labeled PET
      imaging probes, such as peptides, can be synthesized in good chemical and
      radiochemical purity (>98%), satisfactory radiochemical yield of 20-35% (n > 20,
      non-decay corrected) and high specific activity of 40-111 GBq/MUmol (1.1-3.0
      Ci/MUmol). The entire procedure, including the precursor preparation and (18)F
      radiolabeling, takes 7-10 d. 

PMID- 26313479
TI  - Genome-wide mapping of embedded ribonucleotides and other noncanonical
      nucleotides using emRiboSeq and EndoSeq.
AB  - Ribonucleotides are the most common noncanonical nucleotides incorporated into
      the genome of replicating cells. They are efficiently removed by ribonucleotide
      excision repair initiated by RNase H2 cleavage. In the absence of RNase H2, such
      embedded ribonucleotides can be used to track DNA polymerase activity in vivo. To
      determine their precise location in Saccharomyces cerevisiae, we developed
      embedded ribonucleotide sequencing (emRiboSeq), which uses recombinant RNase H2
      to selectively create ligatable 3'-hydroxyl groups, in contrast to alternative
      methods that use alkaline hydrolysis. EmRiboSeq allows reproducible, strand
      specific and potentially quantitative detection of embedded ribonucleotides at
      single-nucleotide resolution. For the genome-wide mapping of other noncanonical
      bases, RNase H2 can be replaced with specific nicking endonucleases in this
      protocol; we term this method endonuclease sequencing (EndoSeq). With the
      protocol taking <5 d to complete, these methods allow the in vivo study of DNA
      replication and repair, including the identification of replication origins and
      termination regions. 

PMID- 26313481
TI  - Corrigendum: Measuring mRNA copy number in individual Escherichia coli cells
      using single-molecule fluorescent in situ hybridization.

PMID- 26313480
TI  - Direct metabolomics for plant cells by live single-cell mass spectrometry.
AB  - Live single-cell mass spectrometry (live MS) provides a mass spectrum that shows
      thousands of metabolite peaks from a single live plant cell within minutes. By
      using an optical microscope, a cell is chosen for analysis and a metal-coated
      nanospray microcapillary tip is used to remove the cell's contents. After adding
      a microliter of ionization solvent to the opposite end of the tip, the trapped
      contents are directly fed into the mass spectrometer by applying a high voltage
      between the tip and the inlet port of the spectrometer to induce nanospray
      ionization. Proteins are not detected because of insufficient sensitivity.
      Metabolite peaks are identified by exact mass or tandem mass spectrometry (MS/MS)
      analysis, and isomers can be separated by combining live MS with ion-mobility
      separation. By using this approach, spectra can be acquired in 10 min. In
      combination with metabolic maps and/or molecular databases, the data can be
      annotated into metabolic pathways; the data analysis takes 30 min to 4 h,
      depending on the MS/MS data availability from databases. This method enables the
      analysis of a number of metabolites from a single cell with rapid sampling at sub
      attomolar-level sensitivity. 

PMID- 26313482
TI  - Corrigendum: Efficient derivation and inducible differentiation of expandable
      skeletal myogenic cells from human ES and patient-specific iPS cells.

PMID- 26313483
TI  - Corrigendum: Primary culture of ovarian surface epithelial cells and ascites
      derived ovarian cancer cells from patients.

PMID- 26313484
TI  - Corrigendum: Gas chromatography mass spectrometry-based metabolite profiling in
      plants.

PMID- 26313486
TI  - SLC1A2 rs3794087 variant and risk for essential tremor: a systematic review and
      meta-analysis.
AB  - BACKGROUND/OBJECTIVE: Recently, a genome-wide association study showed a
      statistically significant association between the rs3794087 single nucleotide
      polymorphism (SNP) in the solute carrier family 1--glial affinity glutamate
      transporter, member 2 (SLC1A2) and the risk for essential tremor (ET). However,
      four further association studies showed controversial results.We carried out a
      systematic review and a meta-analysis including all the studies published on the
      risk of ET related to this SNP. MATERIALS AND METHODS: The systematic review was
      performed using several databases, the meta-analysis was carried out using the
      software Meta-DiSc 1.1.1, and heterogeneity between studies was tested using the
      Q statistic. RESULTS: The meta-analysis included five association studies for the
      SLC1A2 rs3794087 SNP (1925 ET patients, 4914 controls) and the risk for ET. The
      global diagnostic odds ratio (95% confidence intervals) was 1.08 (0.79-1.48) for
      the total group. After excluding data from the discovery series (which was
      responsible for a high degree of heterogeneity), the global diagnostic odds ratio
      (95% confidence intervals) was 0.96 (0.74-1.23). The separate analysis in White
      and Asiatic individuals on the frequency of the minor allele of rs3794087 did not
      show significant differences between ET patients and controls in both subgroups
      after excluding the discovery series. CONCLUSION: The results of the meta
      analysis suggest that rs3794087 is not associated with the risk for ET.

PMID- 26313485
TI  - Escitalopram pharmacogenetics: CYP2C19 relationships with dosing and clinical
      outcomes in autism spectrum disorder.
AB  - BACKGROUND AND AIM: Selective serotonin reuptake inhibitors such as escitalopram
      are commonly used to treat patients with autism spectrum disorder (ASD), but
      there are individual differences in treatment response and tolerability. CYP2C19
      encodes the primary enzyme responsible for escitalopram metabolism and we
      investigated whether polymorphisms in CYP2C19 were related to symptoms and dosing
      in a pharmacogenetic study of ASD. PARTICIPANTS AND METHODS: Participants
      completed the Aberrant Behavior Checklist--Community Version (ABC-CV) weekly for
      6 weeks. Escitalopram was initiated at a dose of 2.5 mg per day, with weekly
      increases to 20 mg unless intolerable side-effects occurred. Three CYP2C19
      metabolizer groups, including ultrarapid, extensive, and reduced metabolizers,
      were examined in relation to symptom improvement and tolerated dose. RESULTS: ABC
      CV scores improved over the course of treatment (P<0.0001). No differences were
      identified in the rate of improvement across metabolizer groups for the ABC-CV
      irritability subscale, which was the primary outcome for clinical symptoms. There
      was a trend for a metabolizer group by time interaction with respect to dose
      (P=0.10). This interaction was driven by the linear rate of change from week 1 to
      study endpoint between the reduced metabolizers and ultrarapid metabolizer groups
      (P=0.05). Post-hoc analyses identified significant differences in the rate of
      dose escalation between ultrarapid metabolizers and extensive metabolizers and
      for ultrarapid metabolizers compared with reduced metabolizers (P's<0.04),
      whereby ultrarapid metabolizers showed a slower rate of change in dose over time.
      CONCLUSION: CYP2C19 ultrarapid metabolizers were associated with reduced
      tolerance to a fixed titration schedule of open-label escitalopram in this ASD
      study sample. Possible explanations may involve the altered kinetics of faster
      metabolizers or previously unknown activities of escitalopram metabolites.

PMID- 26313487
TI  - Effects of sex and the common ADRB1 389 genetic polymorphism on the hemodynamic
      response to dobutamine.
AB  - INTRODUCTION: The ADRB1 389 polymorphism affects responses to the beta-1
      adrenergic receptor (beta1AR) agonist in vitro. Previous studies on its effect on
      the response to dobutamine stress echocardiography were conflicting. In addition,
      sex differences in the response to dobutamine have been suggested. The aim of
      this study was to determine whether the ADRB1 389 polymorphism affects the
      hemodynamic response to dobutamine in healthy individuals including men and
      women. PARTICIPANTS AND METHODS: Healthy individuals were recruited according to
      their ADRB1 49 and 389 genotypes [15 Arg389Arg, 10 Gly389Arg, and 10 Gly389Gly
      individuals, (all Ser49Ser), 21 men and 14 women]. Dobutamine was infused at 2,
      4, and 6 mcg/kg/min. Standardized exercise was performed during the last minute
      of each infusion. RESULTS: Resting heart rate (HR) response to 6 mcg/kg/min
      dobutamine (DeltaHR) was 4.7-fold larger in Arg389Arg than in Gly389Gly [(mean +/
      SD) 12.95 +/- 6.99, 2.75 +/- 1.65 bpm, respectively, PANOVA=0.012]. Renin
      response to dobutamine (DeltaRenin) was 3.9-fold greater in Arg389Arg than in
      Gly389Gly (PANOVA=0.032). Among Arg389Gly heterozygotes, DeltaHR and DeltaRenin
      were not significantly different from either homozygote group. In multivariate
      analysis for DeltaHR variance, significant contributions were observed for
      genotype (P=0.011), baseline HR (P=0.011), and borderline effect for sex
      (P=0.049). CONCLUSION: In healthy individuals, HR and renin responses to
      dobutamine were more than three-fold greater among ADRB1 Arg389 compared with
      Gly389 homozygotes. Future studies on the effect of the ADRB1 389 polymorphism on
      dobutamine stress echocardiography should compare Arg389 and Gly389 homozygotes.

PMID- 26313488
TI  - Fluorescent and photoconductive nanoribbons as a dual-mode sensor for selective
      discrimination of alkyl amines versus aromatic amines.
AB  - Highly fluorescent and photoconductive nanoribbons assembled from an asymmetric
      perylene diimide (PDI) were used as a dual-mode sensor for sensitive and
      selective discrimination of two classes of organic amines in the vapor phase,
      i.e., alkyl amines and aromatic amines. 

PMID- 26313490
TI  - Options and Challenges for Facial Rejuvenation in Patients With Higher
      Fitzpatrick Skin Phototypes.

PMID- 26313489
TI  - MicroRNA Expression Profiling of Human Respiratory Epithelium Affected by
      Invasive Candida Infection.
AB  - Invasive candidiasis is potentially life-threatening systemic fungal infection
      caused by Candida albicans (C. albicans). Candida enters the blood stream and
      disseminate throughout the body and it is often observed in hospitalized
      patients, immunocompromised individuals or those with chronic diseases. This
      infection is opportunistic and risk starts with the colonization of C. albicans
      on mucocutaneous surfaces and respiratory epithelium. MicroRNAs (miRNAs) are
      small non-coding RNAs which are involved in the regulation of virtually every
      cellular process. They regulate and control the levels of mRNA stability and post
      transcriptional gene expression. Aberrant expression of miRNAs has been
      associated in many disease states, and miRNA-based therapies are in progress. In
      this study, we investigated possible variations of miRNA expression profiles of
      respiratory epithelial cells infected by invasive Candida species. For this
      purpose, respiratory epithelial tissues of infected individuals from hospital
      laboratory were accessed before their treatment. Invasive Candida infection was
      confirmed by isolation of Candia albicans from the blood cultures of the same
      infected individuals. The purity of epithelial tissues was assessed by flow
      cytometry (FACSCalibur cytometer; BD Biosciences, Heidelberg, Germany) using
      statin antibody (S-44). TaqMan quantitative real-time PCR (in a TaqMan Low
      Density Array format) was used for miRNA expression profiling. MiRNAs
      investigated, the levels of expression of 55 miRNA were significantly altered in
      infected tissues. Some miRNAs showed dramatic increase (miR-16-1) or decrease of
      expression (miR-17-3p) as compared to control. Gene ontology enrichment analysis
      of these miRNA-targeted genes suggests that Candidal infection affect many
      important biological pathways. In summary, disturbance in miRNA expression levels
      indicated the change in cascade of pathological processes and the regulation of
      respiratory epithelial functions following invasive Candidal infection. These
      findings contribute to our understanding of host cell response to Candidal
      systemic infections. 

PMID- 26313491
TI  - Enmeshed in Controversy: Use of Vaginal Mesh in the Current Medicolegal
      Environment.
AB  - Vaginal mesh has been a valuable tool in the treatment of stress urinary
      incontinence and pelvic organ prolapse. As our knowledge of the long-term
      outcomes and complications of this product has evolved, however, vaginal mesh has
      become the subject of legal scrutiny. Therefore, it is imperative that physicians
      understand pertinent litigation techniques to optimize their informed consent and
      documentation processes and protect themselves. OBJECTIVES: Our objective is to
      familiarize physicians who use vaginal mesh with how law suits involving
      transvaginal mesh are construed. We also describe the current medicolegal
      environment surrounding the use of these products. METHODS: The food and drug
      administration public safety communications, food and drug administration
      Manufacturer and User Facility Device Experience database, and LexisNexis legal
      search engine were used to review data relevant to current vaginal mesh
      litigation. This information was used to create a medicolegal review. RESULTS:
      Litigation involving transvaginal mesh follows 3 paths. The first consists of
      claims against the manufacture of transvaginal mesh with allegations, such as
      design defects, failure to warn, and misrepresentation. The second is a defensive
      legal strategy called the learned intermediary doctrine, used by manufacturers to
      shift liability from themselves to surgeons. The manufacturers claim that the
      duty to inform patients of potential complications lies with the surgeon. The
      third involves claims by patients against surgeons for lack of informed consent,
      alleging that they were not sufficiently informed of potential complications
      associated with transvaginal mesh before insertion. CONCLUSIONS: To lessen the
      liability, a surgeon using transvaginal mesh should inform patients of potential
      complications associated with the products and document informed consent in their
      medical records.

PMID- 26313492
TI  - Tension-Free Vaginal Tape Failure After Robotic Sacrocolpopexy and Tension-Free
      Vaginal Tape for Concomitant Prolapse and Stress Incontinence.
AB  - OBJECTIVE: Evidence of surgical cure with tension free vaginal tape (TVT) is
      robust for isolated stress urinary incontinence, but rigorous studies
      investigating combined prolapse and incontinence are lacking. Our study measured
      cure of stress incontinence in concomitant robotic sacrocolpopexy and retropubic
      sling (TVT). We hypothesized a higher rate of objective failure as measured by
      the cough stress test (CST) compared to failures reported in recent randomized
      trials of TVT in patients without prolapse (aggregate 8% failure). METHODS:
      Prospective cohort of patients with stress incontinence and prolapse, scheduled
      for robotic sacrocolpopexy and TVT. Outcomes assessed at 12 months: CST (primary
      aim), Patient Global Impression of Improvement (PGI-I), Pelvic Floor Distress
      Inventory, and the Sandvik questionnaire. RESULTS: Sixty-six of 77 subjects (86%)
      completed follow-up. Average age was 65 years, 96% were white, with mean body
      mass index of 28.1 kg/m2. Mean parity was 2.7, 50% had a previous hysterectomy.
      Mean leading edge of prolapse was +2.3 cm. All patients underwent the planned
      surgery; additionally, 50% underwent hysterectomy and 38% posterior
      colporrhaphy.The TVT failure (+CST) was 19.7% (95% confidence interval, 11.3%
      31.7%; P < 0.001 compared to 8%). Neither preoperative disease severity, nor
      preoperative prolapse stage affected risk of failure of TVT. Eighty-three percent
      of the subjects were happy or very happy (PGI-I). However, those with a positive
      CST (failure) had significantly less satisfaction on PGI-I, UDI-6, and Pelvic
      Floor Distress Inventory-20. CONCLUSIONS: In this population with advanced
      prolapse, cure of stress urinary incontinence by TVT in setting of robotic
      sacrocolpopexy is lower compared to published trials where prolapse is absent.
      Women are less satisfied when the postoperative CST is positive.

PMID- 26313493
TI  - Does Side Make a Difference? Anatomical Differences Between the Left and Right
      Ureter.
AB  - OBJECTIVES: Seventy to eighty percent of iatrogenic ureteral injuries involve the
      left ureter. We sought to evaluate potential anatomical differences between the
      left and right ureters that may contribute to this discrepancy. METHODS: A
      retrospective image review was undertaken of women who underwent computed
      tomography urograms between 2012 and 2013. The distance to the ureters from the
      midline was measured at the level of the sacral promontory (S1) and the cervix.
      Cervical deviation from the midline was measured, and distance between the cervix
      and ureters was calculated. The anterior-posterior distance between ureters was
      also measured. RESULTS: Ninety-five computed tomography urograms were analyzed.
      The mean age was 56 years (range, 23-92 years). Mean cervical deviation was 2.9
      mm left of the midline (P = 0.028). The left ureter was 4.2 mm more lateral than
      the right at S1 and 2.7 mm more lateral at the cervix (P = 0.000 and 0.001).
      There was no significant difference when accounting for cervical deviation (P =
      0.220). The left ureter was 1.9 mm more anterior than the right at the cervix (P
      = 0.012). Age, body mass index, and ethnicity did not affect the ureteral
      position. CONCLUSIONS: Based on midline measurements, the left ureter courses 2
      to 4 mm more lateral and anterior than does the right ureter. The cervix is also
      positioned 2 to 4 mm to the left side, and as a result, the ureters are actually
      symmetric to the cervix. Although seemingly small, 2 to 4 mm is the width range
      of a Heaney clamp. These anatomic differences may be a contributing factor to the
      increase in ureteral injuries on the left side compared with the right.

PMID- 26313494
TI  - Pelvic Floor Physical Therapy as Primary Treatment of Pelvic Floor Disorders With
      Urinary Urgency and Frequency-Predominant Symptoms.
AB  - OBJECTIVE: To assess the efficacy of pelvic floor physical therapy (PFPT) as
      primary treatment of urinary urgency and frequency symptoms METHODS: We conducted
      a prospective cohort study of women with urinary urgency and frequency symptoms.
      Participants underwent PFPT once or twice per week for 10 weeks. Symptom
      improvement was assessed by validated questionnaires (Pelvic Floor Distress
      Inventory-Short Form 20 and Patient Global Impression of Improvement), voiding
      diaries, and subjective measures. RESULTS: Fifty-seven participants enrolled; 21
      (36.8%) withdrew or completed less than 5 weeks of PFPT. Thirty-one (54.4%) of
      the remaining 36 participants completed 10 weeks of PFPT. The mean age of the
      study group (n = 36) was 48.9 +/- 15.0 years. The primary diagnoses were
      overactive bladder syndrome (n = 24, 66.7%) and painful bladder syndrome (n = 12,
      33.3%). Women attended a median of 14.0 (interquartile range [IQR], 8.0-16.0)
      PFPT visits over a median of 11.9 weeks (IQR, 10.0-18.1). At baseline, the median
      Pelvic Floor Distress Inventory-Short Form 20 score was 79.2 (IQR, 53.1-122.9),
      and decreased to 50.0 (IQR, 25.0-88.5; P < 0.001) after PFPT; the urinary and
      prolapse symptom subscales both decreased significantly. Participants reported a
      decrease from a median of 10.0 voids per day to 8.0 (P < 0.001). On the Patient
      Global Impression of Improvement, 62.5% of women reported that they were "much
      better" or "very much better." CONCLUSIONS: The PFPT with myofasical release
      techniques improves urinary symptoms while avoiding medications and more invasive
      therapies. The high dropout rates suggest that motivation or logistic factors may
      play a significant role in the utilization and success of this treatment option.

PMID- 26313495
TI  - Racial Disparities in Knowledge of Pelvic Floor Disorders Among Community
      Dwelling Women.
AB  - OBJECTIVE: To evaluate racial and ethnic differences in knowledge about
      preventative and curative treatments for pelvic floor disorders (PFD). METHODS:
      The is a secondary analysis of responses from 416 community-dwelling women, aged
      19 to 98 years, living in New Haven County, CT, who completed the Prolapse and
      Incontinence Knowledge Questionnaire. Associations between race/ethnicity
      (categorized as white, African American, and other women of color [combined group
      of Hispanic, Asian or "other" women] and knowledge proficiency about modifiable
      risk factors and treatments for PFD were evaluated. Associations were adjusted
      for age, marital status, socioeconomic status, education, working in a medical
      field, and PFD history. RESULTS: Compared to white women, African American women
      were significantly less likely to recognize childbirth as a risk factor for
      urinary incontinence (UI) and pelvic organ prolapse (POP), to know that exercises
      can help control leakage, and to recognize pessaries as a treatment option for
      POP. Other women of color were also significantly less likely to know about risk
      factors, preventative strategies, and curative treatment options for POP and UI;
      however, these findings may not be generalizable given the heterogeneity and
      small size of this group. CONCLUSIONS: Significant racial disparities exist in
      women's baseline knowledge regarding risk factors and treatment options for POP
      and UI. Targeted, culturally sensitive educational interventions are essential to
      enhancing success in reducing the personal and economic burden of PFD, which have
      proven negative effects on women's quality of life.

PMID- 26313496
TI  - Diabetes, Glycemic Control, and Urinary Incontinence in Women.
AB  - OBJECTIVES: To estimate the association between urinary incontinence and glycemic
      control in women ages 20 to 85 years. METHODS: We included 7270 women from the
      2005 to 2010 National Health and Nutrition Examination Survey, stratified into
      three groups of glycemic control defined by hemoglobin A1c (HbA1c): (i) those
      below the diagnostic threshold (HbA1c < 6.5%), (ii) those with relatively
      controlled diabetes (HbA1c, 6.5-8.5%), and (iii) those with poorly controlled
      diabetes (HbA1c > 8.5%) to allow for a different relationship between glycemic
      control and urinary incontinence within each group. The primary outcomes were the
      presence of any, only stress, only urgency, and mixed urinary incontinence. We
      calculated adjusted risk ratios using Poisson regressions with robust variance
      estimates. RESULTS: The survey-weighted prevalence was 52.9% for any, 27.2% for
      only stress, 9.9% for only urgency, and 15.8% for mixed urinary incontinence.
      Among women with relatively controlled diabetes, each one-unit increase in HbA1c
      was associated with a 13% (95% confidence interval, 1.03-1.25) increase for any
      urinary incontinence and a 34% (95% confidence interval, 1.06-1.69) increase in
      risk for only stress incontinence but was not significantly associated with only
      urgency and mixed incontinence. Other risk factors included body mass index,
      hormone replacement therapy, smoking, and physical activity. CONCLUSIONS:
      Worsening glycemic control is associated with an increased risk for stress
      incontinence for women with relatively controlled diabetes. For those either
      below the diagnostic threshold or with poorly controlled diabetes, the risk may
      be driven by other factors. Further prospective investigation of HbA1c as a
      modifiable risk factor may motivate measures to improve continence in women with
      diabetes.

PMID- 26313497
TI  - Management of Female Anterior Urethral Masses.
AB  - OBJECTIVES: Little is known about anterior female urethral masses and their
      management. Owing to their location, these masses are often missed on physical
      examination and are diagnosed at an advanced stage. METHODS: We report on 2
      anterior urethral masses, with 1 mass arising from an anterior diverticulum.
      RESULTS: Both masses were difficult to identify on examination but were clearly
      delineated by magnetic resonance imaging. In both cases, a biopsy was essential
      for histologic characterization of the mass, predicting prognosis and dictating
      management options. One patient had high-grade clear-cell adenocarcinoma,
      necessitating an anterior exenteration. The other patient had a low-grade
      leiomyoma amenable to conservative management. CONCLUSIONS: Tailored intervention
      for anterior female urethral masses can provide both symptomatic relief and
      mortality benefit.

PMID- 26313498
TI  - Aggressive spinal haemangiomas: imaging correlates to clinical presentation with
      analysis of treatment algorithm and clinical outcomes.
AB  - OBJECTIVE: Aggressive spinal haemangiomas (those with significant osseous
      expansion/extraosseous extension) represent approximately 1% of spinal
      haemangiomas and are usually symptomatic. In this study, we correlate imaging
      findings with presenting symptomatology, review treatment strategies and their
      outcomes and propose a treatment algorithm. METHODS: 16 patients with aggressive
      haemangiomas were retrospectively identified from 1995 to 2013. Imaging was
      assessed for size, location, CT/MR characteristics, osseous expansion and
      extraosseous extension. Presenting symptoms, management and outcomes were
      reviewed. RESULTS: Median patient age was 52 years. Median size was 4.5 cm.
      Lumbar spine was the commonest location (n = 8), followed by thoracic spine (n =
      7) and sacrum (n = 2); one case involved the lumbosacral junction. 12
      haemangiomas had osseous expansion; 13 had extraosseous extension [epidural (n =
      11), pre-vertebral/paravertebral (n = 10) and foraminal (n = 6)]. On CT, 11 had
      accentuated trabeculae and 5 showed lysis. On MRI, eight were T1 hyperintense,
      six were T1 hypointense and all were T2 hyperintense. 11 symptomatic patients
      underwent treatment: chemical ablation (n = 6), angioembolization (n = 3, 2 had
      subsequent surgery), radiotherapy (n = 2, 1 primary and 1 adjuvant) and surgery
      (n = 4). Median follow-up was 20 months. Four of six patients managed only by
      percutaneous methods had symptom resolution. Three of four patients requiring
      surgery had symptom resolution. CONCLUSION: Aggressive haemangiomas cause
      significant morbidity. Treatment is multidisciplinary, with surgery reserved for
      large lesions and those with focal neurological signs. Minimally invasive
      procedures may be successful in smaller lesions. ADVANCES IN KNOWLEDGE:
      Aggressive haemangiomas are rare, but knowledge of their imaging features and
      treatment strategies enhances the radiologist's role in their management.

PMID- 26313499
TI  - Ultrasound-guided interventional procedures around the shoulder.
AB  - Ultrasound is an established modality for shoulder evaluation, being accurate,
      low cost and radiation free. Different pathological conditions can be diagnosed
      using ultrasound and can be treated using ultrasound guidance, such as
      degenerative, traumatic or inflammatory diseases. Subacromial-subdeltoid bursitis
      is the most common finding on ultrasound evaluation for painful shoulder.
      Therapeutic injections of corticosteroids are helpful to reduce inflammation and
      pain. Calcific tendinopathy of rotator cuff affects up to 20% of painful
      shoulders. Ultrasound-guided treatment may be performed with both single- and
      double-needle approach. Calcific enthesopathy, a peculiar form of degenerative
      tendinopathy, is a common and mostly asymptomatic ultrasound finding; dry
      needling has been proposed in symptomatic patients. An alternative is represented
      by autologous platelet-rich plasma injections. Intra-articular injections of the
      shoulder can be performed in the treatment of a variety of inflammatory and
      degenerative diseases with corticosteroids or hyaluronic acid respectively.
      Steroid injections around the long head of the biceps brachii tendon are
      indicated in patients with biceps tendinopathy, reducing pain and humeral
      tenderness. The most common indication for acromion-clavicular joint injection is
      degenerative osteoarthritis, with ultrasound representing a useful tool in
      localizing the joint space and properly injecting various types of drugs
      (steroids, lidocaine or hyaluronic acid). Suprascapular nerve block is an
      approved treatment for chronic shoulder pain non-responsive to conventional
      treatments as well as candidate patients for shoulder arthroscopy. This review
      provides an overview of these different ultrasonography-guided procedures that
      can be performed around the shoulder. 

PMID- 26313500
TI  - Radiological intervention of the hand and wrist.
AB  - The role of radiological guided intervention is integral in the management of
      patients with musculoskeletal pathologies. The key to image-guided procedures is
      to achieve an accurately placed intervention with minimal invasion. This review
      article specifically concentrates on radiological procedures of the hand and
      wrist using ultrasound and fluoroscopic guidance. A systematic literature review
      of the most recent publications relevant to image-guided intervention of the hand
      and wrist was conducted. During this search, it became clear that there is little
      consensus regarding all aspects of image-guided intervention, from the technique
      adopted to the dosage of injectate and the specific drugs used. The aim of this
      article is to formulate an evidence-based reference point which can be utilized
      by radiologists and to describe the most commonly employed techniques. 

PMID- 26313501
TI  - The role of religious affiliation in Christian and unaffiliated bereaved emerging
      adults' use of religious coping.
AB  - Though research on bereavement has grown, few studies have focused on emerging
      adults. To add to the literature, the authors administered the RCOPE to a sample
      of bereaved college students (analyzed sample N = 748) and explored the
      relationship between self-reported religious affiliation and religious coping
      strategies used and endorsed as "most helpful." Results highlight the rich
      topography of bereavement previously unexamined in understudied populations
      (i.e., emerging adults, religiously unaffiliated). Specifically, the
      Christians/affiliated used "negative" religious coping strategies most often, yet
      identified "positive" strategies as "most helpful," whereas the unaffiliated
      instead used "positive" strategies most often and identified "negative"
      strategies as "most helpful." 

PMID- 26313502
TI  - DaPeCa-2: Implementation of fast-track clinical pathways for penile cancer
      shortens waiting time and accelerates the diagnostic process--A comparative
      before-and-after study in a tertiary referral centre in Denmark.
AB  - OBJECTIVE: The aim of this study was to examine the feasibility and impact of a
      fast-track referral pathway on clinical time intervals in penile cancer.
      MATERIALS AND METHODS: This observational study from a tertiary referral centre
      included 263 patients diagnosed before and after the introduction of an
      intervention to reduce clinical time intervals, the Cancer Patient Pathway (CPP).
      The CPP included fast-track referral and set time-frames for units participating
      in cancer diagnosis and treatment, and was introduced for penile cancer in
      Denmark on 1 January 2009. Median time intervals (in calendar days) with
      interquartile range were the main outcome measure. RESULTS: A trend towards
      reduction was observed in all clinical time intervals, with a statistically
      significant reduction in the system interval (p = 0.01) and tertiary centre
      interval (p < 0.0001). The proportion of patients treated within the maximum
      accepted time-frame of 37 days after referral steadily increased after
      implementation of the CPP. In particular, unjustified waiting time was reduced
      significantly. This was mainly achieved through pre-booking of appointments and
      diagnostic time slots by a dedicated clinical coordinator. CONCLUSIONS: To the
      authors' knowledge, this is the first study examining the feasibility and impact
      of an intervention to reduce clinical time intervals in penile cancer. The Danish
      CPP was successful in reducing system and tertiary centre intervals. Future
      interventions need to address the long patient interval. Longer follow-up is
      needed to study the impact of CPP on mortality.

PMID- 26313503
TI  - Use of day 1 early morning cortisol to predict the need for glucocorticoid
      replacement after pituitary surgery.
AB  - BACKGROUND: Assessment of adrenal reserve in patients who have undergone
      pituitary surgery is crucial. However, there is no clear consensus with regards
      to the type and timing of the test that should be used in the immediate post
      operative period. Recently, there has been increased interest in measuring post
      operative cortisol levels. We present our data utilising day 1 post-operative
      early morning cortisol as a tool to assess adrenal reserve in steroid-naive
      patients. METHODS: A retrospective analysis of endoscopic pituitary surgery
      undertaken over a 2-year period. 82 patients underwent 84 surgeries in total.
      Patients who were already on glucocorticoids pre-operatively and patients with
      Cushing's disease, pituitary apoplexy and those without follow-up data were
      excluded, leaving a study group of 44 patients with 45 operations. A 9am day 1
      post-operative cortisol value of > 400 nmol/L was taken as an indicator of
      adequate adrenal reserve. All the patients were reassessed at 6 weeks with a
      standard short synacthen test (SST) using 250 micrograms of intravenous
      synacthen. RESULTS: 22 out of 45 patients had a cortisol value of > 400 nmol/L on
      day 1 post-operatively and were discharged without glucocorticoid
      supplementation. Of these, only 2 patients subsequently failed the SST when
      reassessed at 6-8 weeks. The remaining 23 patients had a cortisol value of < 400
      nmol/L on day 1 post-operatively and were discharged on hydrocortisone 10 mg
      twice daily. At 6-8 weeks, nine continued to show suboptimal stimulated cortisol
      levels whereas the remaining fourteen patients showed adequate adrenal reserve.
      The 9 am cortisol value had high specificity (81.8%) and positive predictive
      value (90.9%) for integrity of the HPA axis. Sensitivity was 58.8% and negative
      predictive value was 39.1%. CONCLUSION: A day 1 post-operative early morning
      cortisol is a useful tool to predict adrenal reserve post-pituitary surgery,
      enabling clinicians to avoid unnecessary blanket glucocorticoid replacement.

PMID- 26313504
TI  - Use of glenoid inclination angle for the assessment of unilateral congenital high
      scapula.
AB  - Little has been reported on the motion of the scapula in Sprengel's deformity.
      Fourteen patients with unilateral congenital high scapula underwent the Woodward
      procedure from 1986 to 2004. The median age of the patients at the time of
      surgery was 4.4 years and the median follow-up duration was 8.8 years. The range
      of motion of the shoulder and the glenoid inclination angle (GIA) were measured
      preoperatively and at the final visit. The range of motion of the shoulder and
      GIA improved at the final visit. There was a positive correlation between the
      maximum abduction angle of the upper limb and GIA at the final visit. 

PMID- 26313505
TI  - Cervical cord compression in pediatrics with hereditary multiple exostoses: a
      report of two cases and review of the literature.
AB  - Hereditary multiple exostoses (HME) generally involves the long tube bone or flat
      bone. Spinal involvement is rare, particularly in young children. We report two
      cases of children with HME who have myelopathy because of cervical spine
      involvement and then review the literature to clarify the clinical
      characteristics of spinal cord HME involvement in young children. In our cases
      and previously reported cases, neurological deficits remained in cases with acute
      onset, but other cases with slow onset showed almost complete recovery after
      surgery. This suggests that the assessment of spinal lesions before trauma is
      very important. 

PMID- 26313506
TI  - Variation potential in higher plants: Mechanisms of generation and propagation.
AB  - Long-distance intercellular electrical signals, including variation potential
      (VP) in higher plants, are a potential mechanism of coordinate functional
      responses in different plant cells under action of stressors. VP, which is caused
      by damaging factors (e.g., heating, crushing), is transient depolarization with
      an irregular shape. It can include a long-term depolarization and fast impulse
      depolarization ('AP-like' spikes). Mechanisms of VP generation and propagation
      are still under investigation. It is probable that VP is a local electrical
      response induced by propagation of hydraulic wave and (or) chemical agent. Both
      hypotheses are based on numerous experimental results but they predict VP
      velocities which are not in a good accordance with speed of variation potential
      propagation. Thus combination of hydraulic and chemical signals is the probable
      mechanism of VP propagation. VP generation is traditionally connected with
      transient H(+)-ATPase inactivation, but AP-like spikes are also connected with
      passive ions fluxes. Ca(2+) influx is a probable mechanism which triggers H(+)
      ATPase inactivation and ions channels activation at VP. 

PMID- 26313507
TI  - EGFR mutation testing of lung cancer patients - Experiences from Vestfold
      Hospital Trust.
AB  - BACKGROUND: Patients with advanced stage lung cancer and somatic mutations in the
      epithelial growth factor receptor (EGFR) gene are currently treated with tyrosine
      kinase inhibitors. The Norwegian Lung Cancer Group (NLCG) recommended EGFR
      testing of all patients with non-small cell lung carcinoma (NSCLC) from June
      2010. From March 2013, testing of squamous cell carcinomas was terminated. We
      have analysed how these recommendation were followed at a medium-sized Norwegian
      hospital and we present data on mutation frequency, retesting and possible
      explanations for missing test results. MATERIAL AND METHODS: All pathology
      reports for patients diagnosed with NSCLC at Vestfold Hospital Trust were
      examined for the period June 2010 to December 2013. Mutation analyses were done
      at the Department of Pathology, Oslo University Hospital. RESULTS: Material was
      sent for EGFR analysis for 256 of the 304 eligible patients diagnosed in the
      period. Material from 48 patients was never sent for EGFR testing, of which five
      samples consisted of too few tumour cells. For the rest, no obvious reason for
      omitting EGFR mutation analyses was identified. During the first six months of
      our study period, material from 25 of 66 NSCLC patients (38%) was not tested,
      whereas only six of the 118 patients (5%) in 2013 were not tested. For 34
      patients, the first tissue specimen contained too few tumour cells and a new
      sample was sent for EGFR analyses for 11 of these. EGFR mutation was detected in
      7.1% of the analysed NSCLC and in 9.4% of adenocarcinomas. DISCUSSION: Especially
      for patients with advanced stages of NSCLC, EGFR mutation status is necessary for
      treatment stratification. Our results show that the guidelines were followed
      increasingly over time for patients diagnosed with NSCLC at the Vestfold Hospital
      Trust. The establishment of interdisciplinary meetings has improved the
      diagnostic routines.

PMID- 26313508
TI  - Asthma in a university campus: a survey of students and staff of Obafemi Awolowo
      University, Ile-Ife, Nigeria.
AB  - BACKGROUND: Asthma continues to be an important cause of morbidity and mortality
      in developing countries. But, its burden among adult populations in university
      campuses is not well described. METHOD: Through a multistage cluster sampling of
      students and staff of the Obafemi Awolowo University, Ile-Ife, Nigeria, we
      obtained a representative sample, each for students and staff. We administered
      the European Community Respiratory Health Survey (ECRHS) screening questionnaire
      to all the respondents. A subgroup did a spirometry test and completed a detailed
      questionnaire. Asthma was considered "possible", if a respondent provided
      affirmative response to symptoms of "wheezing or whistling", "attack of shortness
      of breath", "diagnosed attack of asthma" in the last 12 months or "currently
      taking medicines for asthma". RESULTS: From population of 13,750 students and
      1428 staff of the university, we systematically sampled 2750 (20%) students and
      all the staff. Amongst these, 2372 students and 455 staff completed the screening
      questionnaire. The mean age (SD) of the responders was 21.9 (3.2) and 46.1 (8.9)
      for students and staff and most of them were men; 58.6% and 65.9%, respectively.
      While an estimated 2.6% (95% CI: 1.7-3.5) of students had an asthma attack in the
      preceding 12 months, 14.5% (95% CI: 12.5-16.5) and 25.2% (95% CI: 22.8-27.7)
      reported shortness of breath and nocturnal cough, respectively. The staff
      population reported fewer symptoms. The proportion with "possible asthma" was
      18.2% (95% CI: 16.0-20.4) for students and 8.0% (95% CI: 5.4-10.7) for staff.
      CONCLUSION: The prevalence of asthma is high among students and staff of Obafemi
      Awolowo University, Nigeria.

PMID- 26313509
TI  - Awareness of cognitive deficits in older adults with epilepsy and mild cognitive
      impairment.
AB  - OBJECTIVE: A significant portion of individuals with mild cognitive impairment
      (MCI) experience limited awareness of cognitive deficits. Although older adults
      with epilepsy have comparable cognitive deficits to individuals with MCI, little
      is known about awareness of cognitive deficit in epilepsy. This study compared
      deficit awareness in epilepsy and MCI and examined its relationship with
      neuropsychological performance. METHOD: Sixty-two older adults (31 epilepsy, 31
      MCI) completed neuropsychological testing and the Cognitive Difficulties Scale
      (CDS), a self-report measure of everyday cognitive skills. Informants completed
      the CDS only. Cognitive domain scores were created. CDS composite scores were
      created by summing attention-concentration and language and delayed memory
      factors. Awareness was defined as the difference between patient and informant
      CDS scores, with limited awareness defined as greater informant complaints.
      RESULTS: Neuropsychological performance was similar between groups for all
      domains except that MCI participants had worse delayed memory, t(60) = 2.49, p <
      .05. CDS scores were similar between patient groups (p > .05). Epilepsy informant
      CDS scores were related to poorer immediate memory (r = -.41, p = .02). MCI
      informant CDS scores were related to worse delayed memory (r = -.41, p = .02).
      Limited awareness was found in 29.0% of epilepsy and 61.3% of MCI participants.
      Awareness was not related to cognition in epilepsy but was related to worse
      delayed memory (r = -.41, p = .02) for MCI participants. CONCLUSIONS: Older
      adults with epilepsy and MCI had similar cognitive deficits with the exception of
      greater impairment in delayed memory for MCI patients. There was less awareness
      of deficit in the MCI group, suggesting that delayed memory may be a critical
      factor for deficit awareness. Results argue against executive dysfunction as a
      major contributor to deficit awareness.

PMID- 26313510
TI  - The Prague Stroop Test: Normative standards in older Czech adults and
      discriminative validity for mild cognitive impairment in Parkinson's disease.
AB  - OBJECTIVE: The aim of this study was to provide normative data for older and very
      old Czech adults on the Prague Stroop Test (PST) and to test its discriminative
      validity in individuals with Parkinson's disease mild cognitive impairment (PD
      MCI). METHOD: The construction of the PST was modeled after the Victoria Stroop
      Test. We examined 539 participants aged 60-96 that met strict inclusion criteria.
      After, we compared the PST scores for a group of 45 PD-MCI patients with a
      healthy adult sample (HAS) of 45 age- and education-matched individuals. RESULTS:
      I. In the non-clinical sample, robust age- and education-related influences were
      observed on all PST scores. No gender effect was noted. II. For clinical cases,
      interference condition (PST-C) was able to discriminate between PD-MCI and HAS
      (all scores ps < .01). Area under the curve (AUC) was 77% when a screening cut
      off of <= 27 s was used, showing sensitivity of 82% and specificity of 53%. A
      more conservative diagnostic cut-off of <= 33 s showed sensitivity of 60% and
      specificity of 80%. DISCUSSION: The present study provides PST normative data for
      basic, interference, and error scores stratified by age (60-96 years). PST
      appears to be a helpful tool for the diagnostics of PD-MCI especially in research
      settings at Level II (Litvan et al., 2012) and for PD-MCI attention/working
      memory and executive function subtyping.

PMID- 26313511
TI  - Abnormal tactile pressure perception in Parkinson's disease.
AB  - BACKGROUND/OBJECTIVE: Some of the behavioral disorders associated with
      Parkinson's disease (PD), such as the reduced magnitude of actions (hypometria)
      may be related to an impairment in cognitive disengagement. A reduced ability to
      disengage attention from previous sensory stimuli will alter perception with a
      reduced range of estimated stimulus magnitudes (contraction to the mean). To test
      this disengagement hypothesis, participants with PD were tested to learn whether
      they had abnormal sensory perception with overestimation of the relative
      magnitude of weaker tactile stimuli and underestimation of the relative magnitude
      of stronger tactile stimuli in relation to a reference stimulus. DESIGN/METHOD:
      The participants were 12 people with PD and 12 healthy adults. Test stimuli were
      applied to the palm using Semmes-Weinstein monofilaments (SWM) of 6 magnitudes, 3
      greater and 3 less than a standard stimulus. In each trial, after being
      stimulated with the reference (standard) stimulus, a test monofilament was
      applied, and the participant was asked to provide a numerical estimate of the
      magnitude of the second stimulus relative to the standard. RESULTS: Compared to
      the control group, participants with PD overestimated the magnitudes of the
      tactile stimuli below the standard stimulus and underestimated the magnitudes of
      stimuli above the standard stimulus. CONCLUSIONS: These results demonstrate that
      people with PD likely have a reduced ability to estimate the relative magnitudes
      of tactile sensory stimuli. Whereas deafferentation would alter perception in one
      direction, the impairment of these participants with PD may result from a
      disorder of disengagement, and disorders of disengagement are often due to
      frontal-executive dysfunction.

PMID- 26313513
TI  - Prospective comparison of cognitive effects of carotid endarterectomy versus
      carotid stenting with flow reversal or distal filters.
AB  - OBJECTIVE: It is unclear whether carotid revascularization can improve the
      cognitive problems often observed in patients with carotid stenosis. We examined
      the presence of preoperative disturbances and the effects of different types of
      carotid revascularization on cognition. METHOD: Forty-six patients treated for
      significant carotid stenosis [26 carotid endarterectomy (CEA), 10 transfemoral
      carotid stenting with distal filters (CASdp), and 10 transcervical stenting with
      flow reversal (CASfr)] as well as a matched control group of 26 vascular patients
      without carotid stenosis were included. Patients and controls were tested 1 day
      preoperatively and 1, 6, and 12 months after surgery on 18 neuropsychological
      variables. RESULTS: A significant amount of carotid patients as well as vascular
      controls showed cognitive defects at preoperative testing. None of the
      neuropsychological variables showed significant group differences between CEA,
      CASdp, CASfr, and controls, and only 1 revealed interaction between type of
      revascularization and improvements over time, though this effect dissolved when 2
      outliers were excluded. Thirteen of 18 variables showed improved scores over
      time, regardless of the group. Compared with controls, about 10% of patients
      showed improvements, while 20% showed cognitive deterioration 6 months after
      revascularization. CONCLUSIONS: Results show similar effects for CEA, CASdp, and
      CASfr on cognition. Large practice effects due to repeated testing confirm the
      importance of using control groups in prospective cognition studies. Because of
      the small sample size, this study should be regarded as an exploratory study;
      larger studies on the cognitive consequences of carotid revascularization remain
      warranted.

PMID- 26313514
TI  - The role of obsessive-compulsive symptoms in the perception of insincere speech
      in first-episode psychosis.
AB  - OBJECTIVES: The aim of the present study was to investigate the effects of
      comorbid obsessive-compulsive symptoms (OCS) on the perception of insincere
      speech (e.g., sarcasm and white lies) in patients with first-episode psychosis.
      DESIGN AND METHOD: Participants were 65 patients with nonaffective first-episode
      psychosis (FEP) and 47 healthy controls. The patient group was divided into two
      subgroups, those with (FEP+; n= 38) and those without OCS (FEP-; n = 27). The
      ability to process sarcasm and lie was assessed with the Perception of Social
      Inference Test (PESIT). Severity of psychotic symptoms and OCS was assessed with
      the Positive and Negative Syndrome Scale (PANSS) and the Yale-Brown Obsessive
      Compulsive Scale (Y-BOCS), respectively. RESULTS: Deficits in the perception of
      sarcasm and lie were confirmed in patients with nonaffective first-episode
      psychosis compared to healthy controls. In patients, comorbidity with OCS was
      associated with worse performance on certain aspects of insincere speech (i.e.,
      lie) compared to FEP- patients. Y-BOCS scores correlated significantly with the
      perception of lying. The cognitive factor of the PANSS predicted accuracy on the
      perception of sincere speech, paradoxical sarcasm, and white lies, while the
      presence of OCS predicted accuracy on the perception of sincere speech and white
      lies. CONCLUSIONS: Our finding of impaired counterfactual information processing
      in patients with first-episode psychosis suggests that these deficits are already
      present at illness onset. Presence of OCS appears to have additional deleterious
      effects on the successful interpretation of intentional lying, further supporting
      that these patients are characterized by more extensive cognitive impairment.

PMID- 26313512
TI  - A new semantic list learning task to probe functioning of the Papez circuit.
AB  - INTRODUCTION: List learning tasks are powerful clinical tools for studying
      memory, yet have been relatively underutilized within the functional imaging
      literature. This limits understanding of regions such as the Papez circuit that
      support memory performance in healthy, nondemented adults. METHOD: The current
      study characterized list learning performance in 40 adults who completed a
      semantic list learning task (SLLT) with a Brown-Peterson manipulation during
      functional magnetic resonance imaging (fMRI). Cued recall with semantic cues and
      recognition memory were assessed after imaging. Internal reliability, convergent,
      and discriminant validity were evaluated. RESULTS: Subjects averaged 38% accuracy
      in recall (62% for recognition), with primacy but no recency effects observed.
      Validity and reliability were demonstrated by showing that the SLLT was
      correlated with the California Verbal Learning Test (CVLT), but not with
      executive functioning tests, and by high intraclass correlation coefficient
      across lists for recall (.91). fMRI measurements during encoding (vs. silent
      rehearsal) revealed significant activation in bilateral hippocampus,
      parahippocampus, and bilateral anterior and posterior cingulate cortex. Post hoc
      analyses showed increased activation in anterior and middle hippocampus,
      subgenual cingulate, and mammillary bodies specific to encoding. In addition,
      increasing age was positively associated with increased activation in a diffuse
      network, particularly frontal cortex and specific Papez regions for correctly
      recalled words. Gender differences were specific to left inferior and superior
      frontal cortex. CONCLUSIONS: This is a clinically relevant list learning task
      that can be used in studies of groups for which the Papez circuit is damaged or
      disrupted, in mixed or crossover studies at imaging and clinical sites.

PMID- 26313515
TI  - Enhancing prospective memory in mild cognitive impairment: The role of enactment.
AB  - INTRODUCTION: Prospective memory (PM) is a fundamental requirement for
      independent living which might be prematurely compromised in the
      neurodegenerative process, namely in mild cognitive impairment (MCI), a typical
      prodromal Alzheimer's disease (AD) phase. Most encoding manipulations that
      typically enhance learning in healthy adults are of minimal benefit to AD
      patients. However, there is some indication that these can display a recall
      advantage when encoding is accompanied by the physical enactment of the material.
      The aim of this study was to explore the potential benefits of enactment at
      encoding and cue-action relatedness on memory for intentions in MCI patients and
      healthy controls using a behavioral PM experimental paradigm. METHOD: We report
      findings examining the influence of enactment at encoding for PM performance in
      MCI patients and age- and education-matched controls using a laboratory-based PM
      task with a factorial independent design. RESULTS: PM performance was
      consistently superior when physical enactment was used at encoding and when
      target-action pairs were strongly associated. Importantly, these beneficial
      effects were cumulative and observable across both a healthy and a cognitively
      impaired lifespan as well as evident in the perceived subjective difficulty in
      performing the task. CONCLUSIONS: The identified beneficial effects of enacted
      encoding and semantic relatedness have unveiled the potential contribution of
      this encoding technique to optimize attentional demands through an adaptive
      allocation of strategic resources. We discuss our findings with respect to their
      potential impact on developing strategies to improve PM in AD sufferers.

PMID- 26313516
TI  - Math anxiety and developmental dyscalculia: A study on working memory processes.
AB  - INTRODUCTION: Although many children encounter difficulties in arithmetic, the
      underlying cognitive and emotive factors are still not fully understood. This
      study examined verbal and visuospatial short-term memory (STM) and working memory
      (WM) performance in children with developmental dyscalculia (DD) and high
      mathematics anxiety (MA) compared with typically developing (TD) children.
      METHOD: Groups were matched on reading comprehension performance and IQ as well
      as on general anxiety. We aimed to test whether children with DD and MA were
      differently impaired in verbal and visuospatial STM and WM. Children were
      individually tested with four computerized tasks: two STM tasks (forward verbal
      and visuospatial recall) and two WM tasks (backward verbal and visuospatial
      recall). RESULTS: Relative to children with TD, those with DD did not show
      impairments on the forward or backward verbal tasks, but showed specific
      impairments in the visuospatial WM task. In contrast, children with MA were
      particularly impaired in the verbal WM task. CONCLUSIONS: Knowing the underlying
      cognitive processes that differentiate why children with DD and MA fail in math
      could have both educational and clinical implications.

PMID- 26313517
TI  - Assessing students from multiple years using a single Objective Structured
      Clinical Examination.

PMID- 26313519
TI  - Unraveling the effect of La A-site substitution on oxygen ion diffusion and
      oxygen catalysis in perovskite BaFeO3 by data-mining molecular dynamics and
      density functional theory.
AB  - BaFeO3 (BFO) is a promising parent material for high-temperature oxygen
      catalysis. The effects of La substitution on the oxygen ion diffusion and oxygen
      catalysis in A-site La-substituted BFO are studied by combining data-driven
      molecular dynamics (MD) simulations and density functional theory (DFT)
      calculations. The data-driven MD simulations are capable of providing atomic
      level information regarding oxygen jumps at different sites, bridging the
      resolution gap of analysis between MD and DFT. The simulations identify several
      effects due to the introduction of La. First, according to simple
      electroneutrality considerations and DFT calculations, La tends to decrease the
      concentration of oxygen vacancies in BFO. Second, La substitution lowers the
      activation energy of local oxygen migration, providing faster paths for oxygen
      diffusion. The MD analysis predicts a higher hopping rate through La-containing
      bottlenecks as well as easier oxygen jumps from the La-rich cages and lower dwell
      times of oxygen in those cages. DFT calculations confirm a lower migration energy
      through La-containing bottlenecks. Third, the electrocatalytic activity of the
      material decreases with La, as indicated by a lower O p-band center and higher
      oxygen vacancy formation energies. 

PMID- 26313518
TI  - Relationship between sol-gel conditions and enzyme stability: a case study with
      beta-galactosidase/silica biocatalyst for whey hydrolysis.
AB  - The sol-gel process has been very useful for preparing active and stable
      biocatalysts, with the possibility of being reused. Especially those based on
      silica are well known. However, the study of the enzyme behavior during this
      process is not well understood until now and more, if the surfactant is involved
      in the synthesis mixture. This work is devoted to the encapsulation of beta
      galactosidase from Bacillus circulans in silica by sol-gel process, assisted by
      non-ionic Triton X-100 surfactant. The correlation between enzyme activity
      results for the beta-galactosidase in three different environments (soluble in
      buffered aqueous reference solution, in the silica sol, and entrapment on the
      silica matrix) explains the enzyme behavior under stress conditions offered by
      the silica sol composition and gelation conditions. A stable beta
      galactosidase/silica biocatalyst is obtained using sodium silicate, which is a
      cheap source of silica, in the presence of non-ionic Triton X-100, which avoids
      the enzyme deactivation, even at 40  degrees C. The obtained biocatalyst is used
      in the whey hydrolysis for obtaining high value products from this waste. The
      preservation of the enzyme stability, which is one of the most important
      challenges on the enzyme immobilization through the silica sol-gel, is achieved
      in this study. 

PMID- 26313520
TI  - Anti-infective control in human bronchiolar epithelial cells by mucin phenotypic
      changes following uptake of N-acetyl-L-cysteine.
AB  - PURPOSE: Aspiration pneumonia is infection of the respiratory tract resulting
      from accumulation of sputum in the larynx. N-acetyl-L-cysteine (NAC) might
      regulate mucin (MUC) expression and activate inherent anti-infective system in
      bronchiolar epithelial cells after cellular uptake, and therefore, serve as the
      preventative agent for chronic lung disease including aspiration pneumonia. The
      purpose of this in vitro study was to evaluate the effect of uptake of NAC by
      human bronchiolar epithelial cells on bacterial infection and regulations of
      mucin expression in association with cellular redox status under co-culture with
      a representative pathogen for hospital- and community-acquired pneumonia,
      Streptococcus pneumoniae. MATERIALS AND METHODS: Human bronchiolar epithelial
      cells preincubated with or without 20 mM NAC for 3 h were co-cultured with or
      without bacteria for 8 h and evaluated with respect to cellular redox balance,
      expressions of various types of MUC, proinflammatory cytokines and mediators, and
      bacterial infection state by biochemical, genetic, and immunofluorescent assays.
      RESULTS: Markedly increased intracellular reactive oxygen species and oxidized
      glutathione levels plus increased release and expression of proinflammatory
      cytokines and mediators were observed in cells co-cultured with bacteria. These
      bacteria-induced cellular redox disturbance and proinflammatory events were
      prevented and alleviated by pretreatment with NAC. Cells co-cultured with
      bacteria did not increase expression of anti-infective membranous MUC4 but
      exhibited increases in gel-forming MUC5AC expression and bacterial infection.
      However, NAC-pretreated cells avoided bacterial infection along with enhancement
      of MUC4, but not MUC5AC, expression. CONCLUSION: Uptake of NAC by human
      bronchiolar epithelial cells prevented bacterial infection and upregulated
      membranous, but not gel-forming, MUC expression along with the increase in
      intracellular antioxidant level under co-culture conditions with S. pneumoniae.

PMID- 26313521
TI  - Genome-wide mapping of promoter-anchored interactions with close to single
      enhancer resolution.
AB  - Although the locations of promoters and enhancers have been identified in several
      cell types, we still have limited information on their connectivity. We developed
      HiCap, which combines a 4-cutter restriction enzyme Hi-C with sequence capture of
      promoter regions. Applying the method to mouse embryonic stem cells, we
      identified promoter-anchored interactions involving 15,905 promoters and 71,984
      distal regions. The distal regions were enriched for enhancer marks and
      transcription, and had a mean fragment size of only 699 bp--close to single
      enhancer resolution. High-resolution maps of promoter-anchored interactions with
      HiCap will be important for detailed characterizations of chromatin interaction
      landscapes.

PMID- 26313522
TI  - One-Year Change in the Japanese Version of the Montreal Cognitive Assessment
      Performance and Related Predictors in Community-Dwelling Older Adults.
AB  - OBJECTIVES: To examine the distribution and associated predictors of 1-year
      changes in the Japanese version of the Montreal Cognitive Assessment (MoCA-J) in
      community-dwelling older adults. DESIGN: Prospective cohort study. SETTING:
      Population-based cohort study in Tokyo, Japan. PARTICIPANTS: Individuals aged 65
      to 84 (N = 496). MEASUREMENTS: Multinomial logistic regression analysis was
      performed to estimate the odds of experiencing subsequent improvement in MoCA-J
      performance, as opposed to stable or deteriorating, while simultaneously
      adjusting for baseline MoCA-J score and major confounders. RESULTS: Mean age was
      74.0 +/- 4.8; mean MoCA-J score was 23.7 +/- 3.6. Only 40% had stable MoCA-J
      performance; 30% experienced deterioration and 30% improvement. Age increment,
      hospitalization in previous year, slower Timed Up and Go (TUG) score, and slower
      maximum walking speed were predictive of subsequent MoCA-J performance
      deterioration. CONCLUSION: Slower TUG and walking speed performances were
      independent predictors of short-term MoCA-J deterioration. Research aimed at
      assessing lower-extremity performance-based tests in MCI-related decision-making
      is warranted.

PMID- 26313523
TI  - Clinical significance of D4A in prostate cancer therapy with abiraterone.

PMID- 26313524
TI  - Urinary and anal dysfunction after laparoscopic versus laparotomic radical
      hysterectomy.
AB  - OBJECTIVE: The aim of this study was to compare urinary and anal dysfunction
      after laparoscopic (LRH) and abdominal (ARH) radical hysterectomy for cervical
      cancer. STUDY DESIGN: Consecutive patients who underwent radical hysterectomy for
      treatment of cervical cancer were enrolled in this study and divided into two
      groups, according to the surgical approach. Urinary and anal symptoms were
      evaluated before and 6 months after surgery. RESULTS: Fifty-four women were
      considered: 27 LRH and 27 ARH. Urinary incontinence was significantly more
      frequent both after LRH (37% vs 86.9%, p=0.0004) and after ARH (33.3% vs 100%,
      p<0.0001); urge incontinence (3.7% vs 29.6%, p=0.02) and increased bladder
      sensation (0 vs 22.2%, p=0.02) were significantly more common postoperatively in
      patients undergone ARH. In both groups more patients complain about increase of
      straining during voiding (LRH: 0 vs 34.7%, p=0.009; ARH: 3.7% vs 29.6% p=0.02)
      after surgery. Postoperative constipation by obstructed defecation was more
      frequent after ARH (Wexner score: 0 vs 2, p=0.03) but not after LRH. CONCLUSION:
      From our results, laparoscopic approach for radical hysterectomy seems to reduce
      the postoperative occurrence of urge incontinence, increased bladder sensation
      and constipation by obstructed defecation, in comparison with abdominal radical
      surgery.

PMID- 26313526
TI  - Uterine Fibroids: Correlation of T2 Signal Intensity with Semiquantitative
      Perfusion MR Parameters in Patients Screened for MR-guided High-Intensity Focused
      Ultrasound Ablation.
AB  - PURPOSE: To evaluate the relationships between T2 signal intensity and
      semiquantitative perfusion magnetic resonance (MR) parameters of uterine fibroids
      in patients who were screened for MR-guided high-intensity focused ultrasound
      (HIFU) ablation. MATERIALS AND METHODS: Institutional review board approval was
      granted, and informed consents were waived. One hundred seventy most symptom
      relevant, nondegenerated uterine fibroids (mean diameter, 7.3 cm; range, 3.0-17.2
      cm) in 170 women (mean age, 43.5 years; range, 24-56 years) undergoing screening
      MR examinations for MR-guided HIFU ablation from October 2009 to April 2014 were
      retrospectively analyzed. Fibroid signal intensity was assessed as the ratio of
      the fibroid T2 signal intensity to that of skeletal muscle. Parameters of
      semiquantitative perfusion MR imaging obtained during screening MR examination
      (peak enhancement, percentage of relative peak enhancement, time to peak [in
      seconds], wash-in rate [per seconds], and washout rate [per seconds]) were
      investigated to assess their relationships with T2 signal ratio by using multiple
      linear regression analysis. Correlations between T2 signal intensity and
      independently significant perfusion parameters were then evaluated according to
      fibroid type by using Spearman correlation test. RESULTS: Multiple linear
      regression analysis revealed that relative peak enhancement showed an
      independently significant correlation with T2 signal ratio (Beta = 0.004, P <
      .001). Submucosal intracavitary (n = 20, rho = 0.275, P = .240) and type III (n =
      18, rho = 0.082, P = .748) fibroids failed to show significant correlations
      between perfusion and T2 signal intensity, while significant correlations were
      found for all other fibroid types (rho = 0.411-0.629, P < .05). CONCLUSION: In
      possible candidates for MR-guided HIFU ablation, the T2 signal intensity of
      nondegenerated uterine fibroids showed an independently significant positive
      correlation with relative peak enhancement in most cases, except those of
      submucosal intracavitary or type III fibroids.

PMID- 26313527
TI  - Adult plasticity and cortical reorganization after peripheral lesions.
AB  - Following loss of input due to peripheral lesions, functional reorganization
      occurs in the deprived cortical region in adults. Over a period of hours to
      months, cells in the lesion projection zone (LPZ) begin to respond to novel
      stimuli. This reorganization is mediated by two processes: a reduction of
      inhibition in a gradient throughout the cortex and input remapping via sprouting
      of axonal arbors from cortical regions spatially adjacent to the LPZ, and
      strengthening of pre-existing subthreshold inputs. Together these inputs
      facilitate receptive field remapping of cells in the LPZ. Recent experiments have
      revealed time courses and potential interactions of the mechanisms associated
      with functional reorganization, suggesting that large scale reorganization in the
      adult may utilize plasticity mechanisms prominent during development. 

PMID- 26313525
TI  - Characterization of type I interferon pathway during hepatic differentiation of
      human pluripotent stem cells and hepatitis C virus infection.
AB  - Pluripotent stem cells are being actively studied as a cell source for
      regenerating damaged liver. For long-term survival of engrafting cells in the
      body, not only do the cells have to execute liver-specific function but also
      withstand the physical strains and invading pathogens. The cellular innate immune
      system orchestrated by the interferon (IFN) pathway provides the first line of
      defense against pathogens. The objective of this study is to assess the innate
      immune function as well as to systematically profile the IFN-induced genes during
      hepatic differentiation of pluripotent stem cells. To address this objective, we
      derived endodermal cells (day 5 post-differentiation), hepatoblast (day 15) and
      hepatocyte-like cells (day 21) from human embryonic stem cells (hESCs). Day 5, 15
      and 21 cells were stimulated with IFN-alpha and subjected to IFN pathway
      analysis. Transcriptome analysis was carried out by RNA sequencing. The results
      showed that the IFN-alpha treatment activated STAT-JAK pathway in differentiating
      cells. Transcriptome analysis indicated stage specific expression of classical
      and non-classical IFN-stimulated genes (ISGs). Subsequent validation confirmed
      the expression of novel ISGs including RASGRP3, CLMP and TRANK1 by differentiated
      hepatic cells upon IFN treatment. Hepatitis C virus replication in hESC-derived
      hepatic cells induced the expression of ISGs--LAMP3, ETV7, RASGRP3, and TRANK1.
      The hESC-derived hepatic cells contain intact innate system and can recognize
      invading pathogens. Besides assessing the tissue-specific functions for cell
      therapy applications, it may also be important to test the innate immune function
      of engrafting cells to ensure adequate defense against infections and improve
      graft survival.

PMID- 26313528
TI  - Assessment of Quantum Mechanical Models Based on Resolved Orbital Momentum
      Distributions of n-Butane in the Outer Valence Shell.
AB  - Fully resolved outer valence orbital momentum distributions (MDs) of n-butane
      (C4H10) in the ground electronic state (X1Ag) are studied quantum mechanically
      using RHF/TZVP, density functional theory (DFT) DFT-BP/TZVP, and B3LYP/TZVP
      methods. The orbital MDs are simulated to reflect the recent experimental
      conditions with the plane wave impulse approximation (PWIA) and are compared
      favorably with the available experimental orbital cross sections. However, the
      majority of the outer valence molecular orbitals (MOs) of n-butane has been only
      partially resolved experimentally, forming into three clustered MOs of 7ag + 2bg
      + 6ag, 2au + 6bu and 1bg + 5bu + 5ag. Deconvolution of the clustered MOs is a
      challenge experimentally but rather straightforward theoretically, as the
      inversion is a multiple channel process. The outer valence MOs are crucial to
      understanding the chemical bonding mechanism and the unresolved outer valence
      orbitals cause significant bonding information loss. This work provides an
      orbital based assessment to the quality of the RHF/TZVP, DFT-BP/TZVP, and
      B3LYP/TZVP models using orbital MD information, by decomposing the clustered
      outer valence MOs of n-butane, which also reveals the bonding mechanism of the
      species. 

PMID- 26313529
TI  - Single nucleotide polymorphisms near the inhibin beta B gene on 2q14 are
      associated with pre-eclampsia in Han Chinese women.
AB  - CONTEXT AND OBJECTIVE: Pre-eclampsia (PE) is the most common medical complication
      of pregnancy encountered worldwide. A previous genome-wide association study
      showed that three single nucleotide polymorphisms (SNPs) located near the inhibin
      beta B gene (INHBB) - rs12711941 (T>G), rs7576192 (A>G) and rs7579169 (T>C) -
      were associated with PE in Australian women. The present study was undertaken to
      assess the genetic association between these three SNPs and the risk of PE in Han
      Chinese women. PATIENTS: One hundred and eighty-one pregnant women with PE and
      203 healthy pregnant women (controls) were recruited from the Department of
      Obstetrics and Gynaecology at the Shengjing Hospital of China Medical University
      from October 2012 to June 2013. STUDY DESIGN: PE patients and controls underwent
      clinical and biochemical examination. The three SNPs were genotyped using matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry. PE
      patients were divided into various subgroups for comparison with controls.
      RESULTS: The rs7579169 CC genotype was found to have a significantly higher
      frequency in PE patients than in controls [TT vs TC+CC: odds ratio (OR)=2.278,
      p=0.040], indicating that the C allele of rs7579169 confers a risk for PE
      [OR=1.4440, 95% confidence interval (CI) 1.0517-1.9827, p=0.0229]. The rs7576192
      genotype showed significant differences between controls and multiparous PE
      patients (chi(2)=4.6088, df=1, P=0.0319, OR=0.6379, 95% CI 0.4223-0.9634).
      However, neither allele nor genotype frequencies of rs12711941 differed
      significantly between patients and controls in any genetic models or subgroup
      analyses. Haplotype analysis revealed that the H1 haplotype (G-G-C) was
      associated with PE (OR=1.437, 95% CI 1.034-1.997, p<0.05), whereas the H2
      haplotype (G-G-T) offered protection against PE (OR=0.482, 95% CI 0.232-1.001,
      p<0.05). CONCLUSION: Pregnant Han Chinese women carrying the rs7579169 CC
      genotype and G-G-C haplotype are significantly more likely to develop PE,
      especially late-onset and multiparous cases.

PMID- 26313530
TI  - Analysis of flow and LDL concentration polarization in siphon of internal carotid
      artery: Non-Newtonian effects.
AB  - Carotid siphon is known as one of the risky sites among the human intracranial
      arteries, which is prone to formation of atherosclerotic lesions. Indeed,
      scientists believe that accumulation of low density lipoprotein (LDL) inside the
      lumen is the major cause of atherosclerosis. To this aim, three types of internal
      carotid artery (ICA) siphon have been constructed to examine variations of
      hemodynamic parameters in different regions of the arteries. Providing real
      physiological conditions, blood considered as non-Newtonian fluid and real
      velocity and pressure waveforms have been employed as flow boundary conditions.
      Moreover, to have a better estimation of risky sites, the accumulation of LDL
      particles has been considered, which has been usually ignored in previous
      relevant studies. Governing equations have been discretized and solved via open
      source OpenFOAM software. A new solver has been built to meet essential
      parameters related to the flow and mass transfer phenomena. In contrast to the
      common belief regarding negligible effect of blood non-Newtonian behavior inside
      large arteries, current study suggests that the non-Newtonian blood behavior is
      notable, especially on the velocity field of the U-type model. In addition, it is
      concluded that neglecting non-Newtonian effects underestimates the LDL
      accumulation up to 3% in the U-type model at the inner side of both its bends.
      However, in the V and C type models, non-Newtonian effects become relatively
      small. Results also emphasize that the outer part of the second bend at the
      downstream is also at risk similar to the inner part of the carotid bends.
      Furthermore, from findings it can be implied that the risky sites strongly depend
      on the ICA shape since the extension of the risky sites are relatively larger for
      the V-type model, while the LDL concentrations are higher for the C-type model. 

PMID- 26313532
TI  - Engineering Acoustic Phonons and Electron-Phonon Coupling by the Nanoscale
      Interface.
AB  - Precise engineering of phonon-phonon (ph-ph) and electron-phonon (e-ph)
      interactions by materials design is essential for an in-depth understanding of
      thermal, electrical, and optical phenomena as well as new technology breakthrough
      governed by fundamental physical laws. Due to their characteristic length scale,
      the ph-ph and e-ph interactions can be dramatically modified by nanoscale spatial
      confinement, thus opening up opportunities to finely maneuver underlying coupling
      processes through the interplay of confined size, fundamental length scale, and
      interface. We have combined ultrafast optical spectroscopy with a series of well
      designed nanoscale core-shell structures possessing precisely tunable interface
      to demonstrate for the first time unambiguous experimental evidence of coherent
      interfacial phonon coupling between the core and shell constituents. Such
      interfacially coupled phonons can be impulsively excited through the e-ph
      interaction, in which the critical e-ph coupling constant is further shown to be
      monotonically controlled by tuning the configuration and constituent of core
      shell nanostructure. Precise tunability of elemental physics processes through
      nanoscale materials engineering should not only offer fundamental insights into
      different materials properties but also facilitate design of devices possessing
      desirable functionality and property with rationally tailored nanostructures as
      building blocks. 

PMID- 26313531
TI  - Quantitative assessment of myocardial fibrosis in an age-related rat model by ex
      vivo late gadolinium enhancement magnetic resonance imaging with
      histopathological correlation.
AB  - Late gadolinium enhanced (LGE) cardiac magnetic resonance (CMR) imaging can
      detect the presence of myocardial infarction from ischemic cardiomyopathies
      (ICM). However, it is more challenging to detect diffuse myocardial fibrosis from
      non-ischemic cardiomyopathy (NICM) with this technique due to more subtle and
      heterogeneous enhancement of the myocardium. This study investigates whether high
      resolution LGE CMR can detect age-related myocardial fibrosis using quantitative
      texture analysis with histological validation. LGE CMR of twenty-four rat hearts
      (twelve 6-week-old and twelve 2-year-old) was performed using a 7T MRI scanner.
      Picrosirius red was used as the histopathology reference for collagen staining.
      Fibrosis in the myocardium was quantified with standard deviation (SD) threshold
      methods from the LGE CMR images and 3D contrast texture maps that were computed
      from gray level co-occurrence matrix of the CMR images. There was a significant
      increase of collagen fibers in the aged compared to the young rat histology
      slices (2.60+/-0.27 %LV vs. 1.24+/-0.29 %LV, p<0.01). Both LGE CMR and texture
      images showed a significant increase of myocardial fibrosis in the elderly
      compared to the young rats. Fibrosis in the LGE CMR images correlated strongly
      with histology with the 3 SD threshold (r=0.84, y=0.99x+0.00). Similarly,
      fibrosis in the contrast texture maps correlated with the histology using the 4
      SD threshold (r=0.89, y=1.01x+0.00). High resolution ex-vivo LGE CMR can detect
      the presence of diffuse fibrosis that naturally developed in elderly rat hearts.
      Our results suggest that texture analysis may improve the assessment of
      myocardial fibrosis in LGE CMR images. 

PMID- 26313533
TI  - Chemical Detection of Hydrogen Fluoride by the Phosphorus Congener of Cyclobutane
      1,3-diyl.
AB  - Heteroaryl-substituted air-tolerant 2,4-bis(2,4,6-tri-t-butylphenyl)-1,3
      diphosphacyclobutane-2,4-diyls in the open-shell singlet state were synthesized
      by a sterically promoted regioselective S(N)Ar process. Here we demonstrate that
      these diyls are effective for capturing hydrogen fluoride (HF) generated by
      intermediary base-coordinated HF and amine-stabilized HF reagents. The
      hydrofluorination reaction predominantly occurred on the lambda(3)sigma(3)
      phosphorus atoms to afford the energetically disfavored 1lambda(5),3lambda(5)
      diphosphete. The positively charged t-butyl-substituted phosphorus atom trapped
      the fluoride anion, and the subsequent protonation was controlled by the steric
      effect. X-ray crystallographic analysis and an Atoms in Molecule study of the air
      stable 1lambda(5),3lambda(5)-diphosphete bearing P-H and P-F bonds revealed that
      the delocalized ylidic linkages in the four-membered ring were almost identical,
      in contrast to the nonsymmetrically substituted 2,4-bis(2,4,6-tri-t-butylphenyl)
      1,3-diphosphacyclobutane-2,4-diyl. Hydrofluorination efficiently induced a
      remarkable exchange of visible photoabsorption. The charge-transfer-type
      transition from highest occupied molecular orbital to lowest unoccupied molecular
      orbital was highly tuned, which is advantageous for the facile identification of
      HF. In contrast to hitherto known trapping reagents for HF based on cleavage of
      the H-F bond, several hydrofluorinated P-heterocycles were reconverted into the
      1,3-diphosphacyclobutane-2,4-diyl by treatment with sodium hydride. However, in
      the hydrofluorination of the benzoyl-substituted 1,3-diphosphacyclobutane-2,4
      diyl, fluorination and protonation occurred at the t-butyl-substituted phosphorus
      atom and the skeletal carbon atom, respectively, and the energetically preferable
      1lambda(5),3lambda(3)-dihydrodiphosphete was isolated as a purple-blue
      crystalline compound. These findings are promising not only for the practical
      detection of HF but also for the development of fluorine technology based on the
      chemistry of phosphorus heterocycles.

PMID- 26313534
TI  - Understanding of pH value and its effect on autohydrolysis pretreatment prior to
      poplar chemi-thermomechanical pulping.
AB  - Autohydrolysis pretreatment with different severity factors was performed on
      poplar chips prior to chemi-thermomechanical pulping (CTMP) in order to
      investigate the change in pH value and its effect on the autohydrolysis
      pretreatment. The results showed that the dissolution amount of acetic acid
      increased with raising the severity factor of the pretreatment and declining the
      size of poplar chips, respectively. Besides, a logarithmic relationship between
      the amount of acetic acid released in the autohydrolysis liquor (AHL) and pH
      value of the AHL was observed. The amounts of glucose and xylose (including those
      in the form of monomers, oligomers, and polysaccharides) as well as furfural and
      hydroxymethylfurfural (HMF) also depended on the pH value of the AHL to some
      extent.

PMID- 26313535
TI  - Correction to Route to Benzo- and Pyrido-Fused 1,2,4-Triazinyl Radicals via N'
      (Het)aryl-N'-[2-nitro(het)aryl]hydrazides.

PMID- 26313536
TI  - Monitoring the Photocleaving Dynamics of Colloidal MicroRNA-Functionalized Gold
      Nanoparticles Using Second Harmonic Generation.
AB  - Photoactivated drug delivery systems using gold nanoparticles provide the promise
      of spatiotemporal control of delivery that is crucial for applications ranging
      from regenerative medicine to cancer therapy. In this study, we use second
      harmonic generation (SHG) spectroscopy to monitor the light-activated controlled
      release of oligonucleotides from the surface of colloidal gold nanoparticles.
      MicroRNA is functionalized to spherical gold nanoparticles using a nitrobenzyl
      linker that undergoes photocleaving upon ultraviolet irradiation. The SHG signal
      generated from the colloidal nanoparticle sample is shown to be a sensitive probe
      for monitoring the photocleaving dynamics in real time. The photocleaving
      irradiation wavelength is scanned to show maximum efficiency on resonance at 365
      nm, and the kinetics are investigated at varying irradiation powers to
      demonstrate that the nitrobenzyl photocleaving is a one-photon process.
      Additional characterization methods including electrophoretic mobility
      measurements, extinction spectroscopy, and fluorimetry are used to verify the SHG
      results, leading to a better understanding of the photocleaving dynamics for this
      model oligonucleotide therapeutic delivery system. 

PMID- 26313537
TI  - Energy and antioxidant responses of pacific oyster exposed to trace levels of
      pesticides.
AB  - Here, we assess the physiological effects induced by environmental concentrations
      of pesticides in Pacific oyster Crassostrea gigas. Oysters were exposed for 14 d
      to trace levels of metconazole (0.2 and 2 MUg/L), isoproturon (0.1 and 1 MUg/L),
      or both in a mixture (0.2 and 0.1 MUg/L, respectively). Exposure to trace levels
      of pesticides had no effect on the filtration rate, growth, and energy reserves
      of oysters. However, oysters exposed to metconazole and isoproturon showed an
      overactivation of the sensing-kinase AMP-activated protein kinase alpha
      (AMPKalpha), a key enzyme involved in energy metabolism and more particularly
      glycolysis. In the meantime, these exposed oysters showed a decrease in
      hexokinase and pyruvate kinase activities, whereas 2-DE proteomic revealed that
      fructose-1,6-bisphosphatase (F-1,6-BP), a key enzyme of gluconeogenesis, was up
      regulated. Activities of antioxidant enzymes were higher in oysters exposed to
      the highest pesticide concentrations. Both pesticides enhanced the superoxide
      dismutase activity of oysters. Isoproturon enhanced catalase activity, and
      metconazole enhanced peroxiredoxin activity. Overall, our results show that
      environmental concentrations of metconazole or isoproturon induced subtle changes
      in the energy and antioxidant metabolisms of oysters. 

PMID- 26313538
TI  - Molecular identification of Saint Louis encephalitis virus genotype IV in
      Colombia.
AB  - Saint Louis encephalitis virus (SLEV) is a member of the Japanese-encephalitis
      virus serocomplex of the genus Flavivirus. SLEV is broadly distributed in the
      Americas and the Caribbean Islands, where it is usually transmitted by mosquitoes
      of the genus Culex and primarily to birds and mammalian-hosts. Humans are
      occasionally infected by the virus and are dead-end hosts. SLEV causes
      encephalitis in temperate regions, while in tropical regions of the Americas,
      several human cases and a wide biological diversity of SLEV-strains have been
      reported. The phylogenetic analysis of the envelope (E) protein genes indicated
      eight-genotypes of SLEV with geographic overlap. The present paper describes the
      genotyping of two SLEV viruses detected in mosquito-pools collected in northern
      Colombia (department of Cordoba). We used reverse transcription-polymerase chain
      reaction to amplify a fragment of the E-gene to confirm the virus identity and
      complete E-gene sequencing for phylogenetic analysis and genotyping of the two
      SLEV viruses found circulating in Cordoba. This is the first report of SLEV
      genotype IV in Colombia (Cordoba) in mosquitoes from a region of human
      inhabitation, implicating the risk of human disease due to SLEV infection.
      Physicians should consider SLEV as a possible aetiology for undiagnosed febrile
      and neurologic syndromes among their patients who report exposure to mosquito
      bites.

PMID- 26313539
TI  - Targeting copper in cancer therapy: 'Copper That Cancer'.
AB  - Copper is an essential micronutrient involved in fundamental life processes that
      are conserved throughout all forms of life. The ability of copper to catalyze
      oxidation-reduction (redox) reactions, which can inadvertently lead to the
      production of reactive oxygen species (ROS), necessitates the tight homeostatic
      regulation of copper within the body. Many cancer types exhibit increased
      intratumoral copper and/or altered systemic copper distribution. The realization
      that copper serves as a limiting factor for multiple aspects of tumor
      progression, including growth, angiogenesis and metastasis, has prompted the
      development of copper-specific chelators as therapies to inhibit these processes.
      Another therapeutic approach utilizes specific ionophores that deliver copper to
      cells to increase intracellular copper levels. The therapeutic window between
      normal and cancerous cells when intracellular copper is forcibly increased, is
      the premise for the development of copper-ionophores endowed with anticancer
      properties. Also under investigation is the use of copper to replace platinum in
      coordination complexes currently used as mainstream chemotherapies. In comparison
      to platinum-based drugs, these promising copper coordination complexes may be
      more potent anticancer agents, with reduced toxicity toward normal cells and they
      may potentially circumvent the chemoresistance associated with recurrent platinum
      treatment. In addition, cancerous cells can adapt their copper homeostatic
      mechanisms to acquire resistance to conventional platinum-based drugs and certain
      copper coordination complexes can re-sensitize cancer cells to these drugs. This
      review will outline the biological importance of copper and copper homeostasis in
      mammalian cells, followed by a discussion of our current understanding of copper
      dysregulation in cancer, and the recent therapeutic advances using copper
      coordination complexes as anticancer agents. 

PMID- 26313541
TI  - Enhanced diffusion and mobile fronts in a simple lattice model of glass-forming
      liquids.
AB  - The diffusion of mobility in bulk and thin film fluids near their glass
      transition is examined with a kinetic lattice model, and compared to recent
      experiments on bulk liquids and vapor-deposited thin film glasses. The "limited
      mobility" (LM) lattice model exhibits dynamic heterogeneity of mobility when the
      fluid is near its kinetic arrest transition; a finite-parameter second-order
      critical point in the LM model bearing strong resemblance to the glass transition
      in real fluids. The spatial heterogeneity of mobility near kinetic arrest leads
      to dynamics that violate the Stokes-Einstein relation. To make connections with
      experiment, LM model simulations of self-diffusion constants in fluids near
      kinetic arrest are compared to those in two organic glass-formers. In addition,
      simulations of mobility in films that have been temperature-jumped above kinetic
      arrest (starting from an arrested state) are carried out. The films develop a
      "front" of mobility at their free surface that progresses into the film interior
      at a constant rate, thereby mobilising the entire film to fluidity. The velocity
      of the front scales with the self-diffusion constant for analogous bulk systems
      an observation consistent with experiments on vapor-deposited molecular thin
      films. 

PMID- 26313540
TI  - An unusual role of folate in the self-assembly of heparin-folate conjugates into
      nanoparticles.
AB  - Tumor targeting agents including antibodies, peptides, and small molecules, are
      often used to improve the delivery efficiency of nanoparticles. Despite numerous
      studies investigating the abilities of targeting agents to increase the
      accumulation of nanosized therapeutics within diseased tissues, little attention
      has been focused on how these ligands can affect the self-assembly of the
      nanoparticle's modified polymer constituents upon chemical conjugation. Here we
      present an actively tumor targeted nanoparticle constructed via the self-assembly
      of a folate modified heparin. Folate conjugation unexpectedly allowed the self
      assembly of heparin, where a majority of the folate molecules (>80%) resided
      inside the core of the nanoparticle. The folate-heparin nanoparticles could also
      physically encapsulate lipophilic fluorescent dyes, enabling the use of the
      constructs as activatable fluorescent probes for targeted in vivo tumor imaging. 

PMID- 26313542
TI  - Hemisphere, gender and age-related effects on iron deposition in deep gray matter
      revealed by quantitative susceptibility mapping.
AB  - The purpose of this work was to investigate the effects of hemispheric location,
      gender and age on susceptibility value, as well as the association between
      susceptibility value and diffusional metrics, in deep gray matter. Iron content
      was estimated in vivo using quantitative susceptibility mapping. Microstructure
      was probed using diffusional kurtosis imaging. Regional susceptibility and
      diffusional metrics were measured for the putamen, caudate nucleus, globus
      pallidus, thalamus, substantia nigra and red nucleus in 42 healthy adults (age
      range 25-78 years). Susceptibility value was significantly higher in the left
      than the right side of the caudate nucleus (P = 0.043) and substantia nigra (P <
      0.001). Women exhibited lower susceptibility values than men in the thalamus (P <
      0.001) and red nucleus (P = 0.032). Significant age-related increases of
      susceptibility were observed in the putamen (P < 0.001), red nucleus (P < 0.001),
      substantia nigra (P = 0.004), caudate nucleus (P < 0.001) and globus pallidus (P
      = 0.017). The putamen exhibited the highest rate of iron accumulation with aging
      (slope of linear regression = 0.73 * 10(-3) ppm/year), which was nearly twice
      those in substantia nigra (slope = 0.40 * 10(-3) ppm/year) and caudate nucleus
      (slope = 0.39 * 10(-3) ppm/year). Significant positive correlations between the
      susceptibility value and diffusion measurements were observed for fractional
      anisotropy (P = 0.045) and mean kurtosis (P = 0.048) in the putamen without
      controlling for age. Neither correlation was significant after controlling for
      age. Hemisphere, gender and age-related differences in iron measurements were
      observed in deep gray matter. Notably, the putamen exhibited the highest rate of
      increase in susceptibility with aging. Correlations between susceptibility value
      and microstructural measurements were inconclusive. These findings could provide
      new clues for unveiling mechanisms underlying iron-related neurodegenerative
      diseases.

PMID- 26313543
TI  - Chemical ordering phenomena in nanostructured FePt: Monte Carlo simulations.
AB  - Free-surface-induced L10 chemical long-range ordering phenomena in a nanolayer, a
      nanowire and a cubic nanoparticle of FePt were studied by means of Monte Carlo
      simulations. The system was modeled with nearest-neighbor and next-nearest
      neighbor interatomic pair interactions deduced from ab initio calculations. The
      generated samples, the dimensionality of which was determined by appropriate
      periodic boundary conditions imposed upon the generated supercells, were
      initially either perfectly ordered in the c-variant L10 superstructure ((001)
      oriented monatomic planes), or completely disordered in the fcc crystalline
      structure. Vacancy-mediated creation of equilibrium atomic configurations was
      modelled by relaxing the systems at temperatures below the 'order-disorder'
      transition point using the Glauber algorithm implemented with the vacancy
      mechanism of atomic migration. The (100)-type-surface-induced heterogeneous
      nucleation of L10-order domains was observed and quantified by means of an
      original parameterization enabling selective determination of volume fractions of
      particular L10-variants. Due to the specific competition between the three kinds
      of (100)-type free surfaces, the initial c-L10 variant long-range order appeared
      to be the most stable in the cubic nanoparticle. The initially disordered samples
      were transformed by the creation of a specific L10 domain structure with a mosaic
      of particular L10-variant domains at the surfaces and almost homogeneous long
      range order in the inner volume. The analysis of correlation effects revealed
      that chemical ordering was initiated at the free surfaces. 

PMID- 26313544
TI  - Anti-herpes simplex virus activities of bioactive extracts from Antrodia
      camphorata mycelia.
AB  - BACKGROUND: Antrodia camphorata, a traditional Chinese medicine, is widely used
      in the treatment of liver diseases and cancers. Anti-inflammatory properties have
      also been described. HSV infection represents one of the most serious public
      health concerns globally because of its devastating impact. Searching for new
      antiviral agents, especially those with different mechanisms of action, is a
      crucial goal and there is an unmet need for alternative and complementary therapy
      against HSV infection. In this study, anti-herpes screening was performed with
      extracts from A. camphorata mycelia. METHODS: MTT assay, fractional inhibitory
      concentration index and median-effect principle were used to evaluate antiviral
      activity and to calculate drug combination effect. RESULTS: Crude ethanol
      extracts and isolated constituents showed inhibition of HSV replication at a very
      low concentration. Fraction A and antrodin A showed viral inhibitory effect with
      reduction of viral cell-to-cell spread. In addition, neither fraction A nor
      antrodin A showed interaction in combination with acyclovir. CONCLUSIONS: A.
      camphorata mycelia and antrodin A might have potential use as anti-HSV agents and
      are promising candidates for future antiviral drug design.

PMID- 26313545
TI  - Correction: Bayesian Sensitivity Analysis of a Cardiac Cell Model Using a
      Gaussian Process Emulator.

PMID- 26313546
TI  - Effect of Organic and Conventional Management on Bio-Functional Quality of
      Thirteen Plum Cultivars (Prunus salicina Lindl.).
AB  - In this study, thirteen Japanese plum cultivars (Prunus salicina Lindl.) grown
      under conventional and organic conditions were compared to evaluate the influence
      of the culture system on bioactive compounds. Their organic acids content (malic,
      citric, tartaric, succinic, shikimic, ascorbic and fumaric acid), total
      polyphenols, total anthocyanins, total carotenoids and antioxidant capacity
      (FRAP, ABTS) were evaluated. The study was performed during two consecutive
      seasons (2012 and 2013) in two experimental orchards located at the IFAPA centre
      Las Torres-Tomejil (Seville, SW Spain). The culture system affected all the
      studied parameters except for total carotenoid content. The organic plums had
      significantly higher polyphenol and anthocyanin concentrations and a greater
      antioxidant capacity. Additionally, significant differences between cultivars
      were also found. 'Showtime' and 'Friar' were the cultivars with the highest
      polyphenol concentration and antioxidant capacity. 'Black Amber' had the highest
      anthocyanin content and 'Larry Ann' and 'Songold' the highest carotenoid content.
      'Sapphire' and 'Black amber' were the cultivars with the highest concentration of
      ascorbic acid. Our results showed a strong year effect. In conclusion, organic
      management had an impact on the production of phytochemical compounds in plums.

PMID- 26313547
TI  - Sediment-phosphorus dynamics can shift aquatic ecology and cause downstream
      legacy effects after wildfire in large river systems.
AB  - Global increases in the occurrence of large, severe wildfires in forested
      watersheds threaten drinking water supplies and aquatic ecology. Wildfire effects
      on water quality, particularly nutrient levels and forms, can be significant. The
      longevity and downstream propagation of these effects as well as the geochemical
      mechanisms regulating them remain largely undocumented at larger river basin
      scales. Here, phosphorus (P) speciation and sorption behavior of suspended
      sediment were examined in two river basins impacted by a severe wildfire in
      southern Alberta, Canada. Fine-grained suspended sediments (<125 MUm) were
      sampled continuously during ice-free conditions over a two-year period (2009
      2010), 6 and 7 years after the wildfire. Suspended sediment samples were
      collected from upstream reference (unburned) river reaches, multiple tributaries
      within the burned areas, and from reaches downstream of the burned areas, in the
      Crowsnest and Castle River basins. Total particulate phosphorus (TPP) and
      particulate phosphorus forms (nonapatite inorganic P, apatite P, organic P), and
      the equilibrium phosphorus concentration (EPC0 ) of suspended sediment were
      assessed. Concentrations of TPP and the EPC0 were significantly higher downstream
      of wildfire-impacted areas compared to reference (unburned) upstream river
      reaches. Sediments from the burned tributary inputs contained higher levels of
      bioavailable particulate P (NAIP) - these effects were also observed downstream
      at larger river basin scales. The release of bioavailable P from postfire, P
      enriched fine sediment is a key mechanism causing these effects in gravel-bed
      rivers at larger basin scales. Wildfire-associated increases in NAIP and the EPC0
      persisted 6 and 7 years after wildfire. Accordingly, this work demonstrated that
      fine sediment in gravel-bed rivers is a significant, long-term source of in
      stream bioavailable P that contributes to a legacy of wildfire impacts on
      downstream water quality, aquatic ecology, and drinking water treatability. 

PMID- 26313548
TI  - Twenty-Eight Years of Poliovirus Replication in an Immunodeficient Individual:
      Impact on the Global Polio Eradication Initiative.
AB  - There are currently huge efforts by the World Health Organization and partners to
      complete global polio eradication. With the significant decline in poliomyelitis
      cases due to wild poliovirus in recent years, rare cases related to the use of
      live-attenuated oral polio vaccine assume greater importance. Poliovirus strains
      in the oral vaccine are known to quickly revert to neurovirulent phenotype
      following replication in humans after immunisation. These strains can transmit
      from person to person leading to poliomyelitis outbreaks and can replicate for
      long periods of time in immunodeficient individuals leading to paralysis or
      chronic infection, with currently no effective treatment to stop excretion from
      these patients. Here, we describe an individual who has been excreting type 2
      vaccine-derived poliovirus for twenty eight years as estimated by the molecular
      clock established with VP1 capsid gene nucleotide sequences of serial isolates.
      This represents by far the longest period of excretion described from such a
      patient who is the only identified individual known to be excreting highly
      evolved vaccine-derived poliovirus at present. Using a range of in vivo and in
      vitro assays we show that the viruses are very virulent, antigenically drifted
      and excreted at high titre suggesting that such chronic excreters pose an obvious
      risk to the eradication programme. Our results in virus neutralization assays
      with human sera and immunisation-challenge experiments using transgenic mice
      expressing the human poliovirus receptor indicate that while maintaining high
      immunisation coverage will likely confer protection against paralytic disease
      caused by these viruses, significant changes in immunisation strategies might be
      required to effectively stop their occurrence and potential widespread
      transmission. Eventually, new stable live-attenuated polio vaccines with no risk
      of reversion might be required to respond to any poliovirus isolation in the post
      eradication era. 

PMID- 26313550
TI  - Structure and Conformation of the Carotenoids in Human Retinal Macular Pigment.
AB  - Human retinal macular pigment (MP) is formed by the carotenoids lutein and
      zeaxanthin (including the isomer meso-zeaxanthin). MP has several functions in
      improving visual performance and protecting against the damaging effects of
      light, and MP levels are used as a proxy for macular health-specifically, to
      predict the likelihood of developing age-related macular degeneration. While the
      roles of these carotenoids in retinal health have been the object of intense
      study in recent years, precise mechanistic details of their protective action
      remain elusive. We have measured the Raman signals originating from MP
      carotenoids in ex vivo human retinal tissue, in order to assess their structure
      and conformation. We show that it is possible to distinguish between lutein and
      zeaxanthin, by their excitation profile (related to their absorption spectra) and
      the position of their nu1 Raman mode. In addition, analysis of the nu4 Raman band
      indicates that these carotenoids are present in a specific, constrained
      conformation in situ, consistent with their binding to specific proteins as
      postulated in the literature. We discuss how these conclusions relate to the
      function of these pigments in macular protection. We also address the
      possibilities for a more accurate, consistent measurement of MP levels by Raman
      spectroscopy. 

PMID- 26313551
TI  - Asymmetric Epoxidation of Alkylidenemalononitriles: Key Step for One-Pot Approach
      to Enantioenriched 3-Substituted Piperazin-2-ones.
AB  - The first enantioselective epoxidation of readily available
      alkylidenemalononitriles has been developed by using a multifunctional cinchona
      derived thiourea as the organocatalyst and cumyl hydroperoxide as the oxidant. A
      new simple one-pot asymmetric epoxidation/SN2 ring-opening reaction with 1,2
      diamines leading to important enantioenriched heterocycles, i.e. 3-substituted
      piperazin-2-ones, has been established. 

PMID- 26313549
TI  - Gene Diversification of an Emerging Pathogen: A Decade of Mutation in a Novel
      Fish Viral Hemorrhagic Septicemia (VHS) Substrain since Its First Appearance in
      the Laurentian Great Lakes.
AB  - Viral Hemorrhagic Septicemia virus (VHSv) is an RNA rhabdovirus, which causes one
      of the world's most serious fish diseases, infecting >80 freshwater and marine
      species across the Northern Hemisphere. A new, novel, and especially virulent
      substrain-VHSv-IVb-first appeared in the Laurentian Great Lakes about a decade
      ago, resulting in massive fish kills. It rapidly spread and has genetically
      diversified. This study analyzes temporal and spatial mutational patterns of VHSv
      IVb across the Great Lakes for the novel non-virion (Nv) gene that is unique to
      this group of novirhabdoviruses, in relation to its glycoprotein (G),
      phosphoprotein (P), and matrix (M) genes. Results show that the Nv-gene has been
      evolving the fastest (k = 2.0 x 10-3 substitutions/site/year), with the G-gene at
      ~1/7 that rate (k = 2.8 x 10-4). Most (all but one) of the 12 unique Nv-
      haplotypes identified encode different amino acids, totaling 26 changes. Among
      the 12 corresponding G-gene haplotypes, seven vary in amino acids with eight
      total changes. The P- and M- genes are more evolutionarily conserved, evolving at
      just ~1/15 (k = 1.2 x 10-4) of the Nv-gene's rate. The 12 isolates contained four
      P-gene haplotypes with two amino acid changes, and six M-gene haplotypes with
      three amino acid differences. Patterns of evolutionary changes coincided among
      the genes for some of the isolates, but appeared independent in others. New viral
      variants were discovered following the large 2006 outbreak; such differentiation
      may have been in response to fish populations developing resistance, meriting
      further investigation. Two 2012 variants were isolated by us from central Lake
      Erie fish that lacked classic VHSv symptoms, having genetically distinctive Nv-,
      G-, and M-gene sequences (with one of them also differing in its P-gene); they
      differ from each other by a G-gene amino acid change and also differ from all
      other isolates by a shared Nv-gene amino acid change. Such rapid evolutionary
      differentiation may allow new viral variants to evade fish host recognition and
      immune responses, facilitating long-time persistence along with expansion to new
      geographic areas.

PMID- 26313552
TI  - Self-regulated learning and academic performance in medical education.
AB  - CONTENT: Medical schools aim to graduate medical doctors who are able to self
      regulate their learning. It is therefore important to investigate whether medical
      students' self-regulated learning skills change during medical school. In
      addition, since these skills are expected to be helpful to learn more
      effectively, it is of interest to investigate whether these skills are related to
      academic performance. METHODS: In a cross-sectional design, the Self-Regulation
      of Learning Self-Report Scale (SRL-SRS) was used to investigate the change in
      students' self-regulated learning skills. First and third-year students (N = 949,
      81.7%) SRL-SRS scores were compared with ANOVA. The relation with academic
      performance was investigated with multinomial regression analysis. RESULTS: Only
      one of the six skills, reflection, significantly, but positively, changed during
      medical school. In addition, a small, but positive relation of monitoring,
      reflection, and effort with first-year GPA was found, while only effort was
      related to third-year GPA. CONCLUSIONS: The change in self-regulated learning
      skills is minor as only the level of reflection differs between the first and
      third year. In addition, the relation between self-regulated learning skills and
      academic performance is limited. Medical schools are therefore encouraged to re
      examine the curriculum and methods they use to enhance their students' self
      regulated learning skills. Future research is required to understand the limited
      impact on performance.

PMID- 26313553
TI  - Clausmarin A, Potential Immunosuppressant Revealed by Yeast-Based Assay and
      Interleukin-2 Production Assay in Jurkat T Cells.
AB  - Small-molecule inhibitors of Ca2+-signaling pathways are of medicinal importance,
      as exemplified by the immunosuppressants FK506 and cyclosporin A. Using a yeast
      based assay devised for the specific detection of Ca2+-signaling inhibitors,
      clausmarin A, a previously reported terpenoid coumarin, was identified as an
      active substance. Here, we investigated the likely mechanism of clausmarin A
      action in yeast and Jurkat T-cells. In the presence of 100 mM CaCl2 in the growth
      medium of Ca2+-sensitive Deltazds1 strain yeast, clausmarin A exhibited a dose
      dependent alleviation of various defects due to hyperactivation of Ca2+
      signaling, such as growth inhibition, polarized bud growth and G2 phase cell
      cycle arrest. Furthermore, clausmarin A inhibited the growth of Deltampk1
      (lacking the Mpk1 MAP kinase pathway) but not Deltacnb1 (lacking the calcineurin
      pathway) strain, suggesting that clausmarin A inhibited the calcineurin pathway
      as presumed from the synthetic lethality of these pathways. Furthermore,
      clausmarin A alleviated the serious defects of a strain expressing a
      constitutively active form of calcineurin. In the human Jurkat T-cell line,
      clausmarin A exhibited a dose-dependent inhibition of IL-2 production and IL-2
      gene transcription, as well as an inhibition of NFAT dephosphorylation. The
      effects of clausmarin A observed in both yeast and Jurkat cells are basically
      similar to those of FK506. Our study revealed that clausmarin A is an inhibitor
      of the calcineurin pathway, and that this is probably mediated via inhibition of
      calcineurin phosphatase activity. As such, clausmarin A is a potential
      immunosuppressant. 

PMID- 26313556
TI  - Depression Dimensions: Integrating Clinical Signs and Symptoms from the
      Perspectives of Clinicians and Patients.
AB  - BACKGROUND: Several studies have recognized that depression is a multidimensional
      construct, although the scales that are currently available have been shown to be
      limited in terms of the ability to investigate the multidimensionality of
      depression. The objective of this study is to integrate information from
      instruments that measure depression from different perspectives-a self-report
      symptomatic scale, a clinician-rated scale, and a clinician-rated scale of
      depressive signs-in order to investigate the multiple dimensions underlying the
      depressive construct. METHODS: A sample of 399 patients from a mood disorders
      outpatient unit was investigated with the Beck Depression Inventory (BDI), the
      Hamilton Depression Rating Scale (HDRS), and the Core Assessment of Psychomotor
      Change (CORE). Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis
      (CFA) were used to investigate underlying dimensions of depression, including
      item level analysis with factor loadings and item thresholds. RESULTS: A solution
      of six depression dimensions has shown good-fit to the data, with no cross
      loading items, and good interpretability. Item-level analysis revealed that the
      multidimensional depressive construct might be organized into a continuum of
      severity in the following ascending order: sexual, cognitive, insomnia, appetite,
      non-interactiveness/motor retardation, and agitation. CONCLUSION: An integration
      of both signs and symptoms, as well as the perspectives of clinicians and
      patients, might be a good clinical and research alternative for the investigation
      of multidimensional issues within the depressive syndrome. As predicted by
      theoretical models of depression, the melancholic aspects of depression (non
      interactiveness/motor retardation and agitation) lie at the severe end of the
      depressive continuum.

PMID- 26313554
TI  - The value of protein structure classification information-Surveying the
      scientific literature.
AB  - The Structural Classification of Proteins (SCOP) and Class, Architecture,
      Topology, Homology (CATH) databases have been valuable resources for protein
      structure classification for over 20 years. Development of SCOP (version 1)
      concluded in June 2009 with SCOP 1.75. The SCOPe (SCOP-extended) database offers
      continued development of the classic SCOP hierarchy, adding over 33,000
      structures. We have attempted to assess the impact of these two decade old
      resources and guide future development. To this end, we surveyed recent articles
      to learn how structure classification data are used. Of 571 articles published in
      2012-2013 that cite SCOP, 439 actually use data from the resource. We found that
      the type of use was fairly evenly distributed among four top categories: A) study
      protein structure or evolution (27% of articles), B) train and/or benchmark
      algorithms (28% of articles), C) augment non-SCOP datasets with SCOP
      classification (21% of articles), and D) examine the classification of one
      protein/a small set of proteins (22% of articles). Most articles described
      computational research, although 11% described purely experimental research, and
      a further 9% included both. We examined how CATH and SCOP were used in 158
      articles that cited both databases: while some studies used only one dataset, the
      majority used data from both resources. Protein structure classification remains
      highly relevant for a diverse range of problems and settings.

PMID- 26313557
TI  - Prophylactic Subclavian Artery Intraaortic Balloon Counter-Pulsation is Safe in
      High-Risk Cardiac Surgery Patients.
AB  - The objective of this study was to determine the safety of prophylactic
      subclavian artery intraaortic balloon pumps (SCA-IABP) in high-risk cardiac
      surgery patients as a bridge to recovery (BTR). From November 2011 to January
      2013, 11 consecutive patients at three institutions underwent prophylactic
      insertion of a SCA-IABP as a BTR. All patients (n = 11) had preoperative ejection
      fractions of 30% or less. Patients concurrently underwent one or a combination of
      the following procedures: coronary artery bypass grafting, mitral valve surgery,
      aortic valve replacement, left ventricular aneurysm resection, and
      ventricular/atrial septal defect closure. The primary outcome measure was a
      composite endpoint of device-related complications (including limb ischemia,
      stroke, device failure, bleeding requiring reoperation, brachial plexus injury,
      device-related infection, and vascular complications) and in-hospital mortality.
      Secondary outcome measures included interval to patient ambulation and
      postoperative length of stay. There were no device-related complications or in
      hospital mortalities in this cohort of 11 consecutive patients. Mean time to
      ambulation, balloon pump support, and postoperative length of stay were 3.70 +/-
      2.50 days, 8.50 +/- 7.00 days, and 15.9 +/- 8.25 days, respectively. Prophylactic
      SCA-IABPs appear to be safe in high-risk cardiac surgery patients as a BTR. 

PMID- 26313558
TI  - Necitumumab in Metastatic Squamous Cell Lung Cancer: Establishing a Value-Based
      Cost.
AB  - IMPORTANCE: The SQUIRE trial demonstrated that adding necitumumab to chemotherapy
      for patients with metastatic squamous cell lung cancer (mSqCLC) increased median
      overall survival by 1.6 months (hazard ratio, 0.84). However, the costs and value
      associated with this intervention remains unclear. Value-based pricing links the
      price of a drug to the benefit that it provides and is a novel method to
      establish prices for new treatments. OBJECTIVE: To evaluate the range of drug
      costs for which adding necitumumab to chemotherapy could be considered cost
      effective. DESIGN, SETTING, AND PARTICIPANTS: We developed a Markov model using
      data from multiple sources, including the SQUIRE trial, which compared standard
      chemotherapy with and without necitumumab as first-line treatment of mSqCLC, to
      evaluate the costs and patient life expectancies associated with each regimen. In
      the analysis, patients were modeled to receive gemcitabine and cisplatin for 6
      cycles or gemcitabine, cisplatin, and necitumumab for 6 cycles followed by
      maintenance necitumumab. Our model's clinical inputs were the survival estimates
      and frequency of adverse events (AEs) described in the SQUIRE trial. Log-logistic
      models were fitted to the survival distributions in the SQUIRE trial. The cost
      inputs included drug costs, based on the Medicare average sale prices, and costs
      for drug administration and management of AEs, based on Medicare reimbursement
      rates (all in 2014 US dollars). MAIN OUTCOMES AND MEASURES: We evaluated
      incremental cost-effectiveness ratios (ICERs) for the use of necitumumab across a
      range of values for its cost. Model robustness was assessed by probabilistic
      sensitivity analyses, based on 10 000 Monte Carlo simulations, sampling values
      from the distributions of all model parameters. RESULTS: In the base case
      analysis, the addition of necitumumab to the treatment regimen produced an
      incremental survival benefit of 0.15 life-years and 0.11 quality-adjusted life
      years (QALYs). The probabilistic sensitivity analyses established that when
      necitumumab cost less than $563 and less than $1309 per cycle, there was 90%
      confidence that the ICER for adding necitumumab would be less than $100 000 per
      QALY and less than $200 000 per QALY, respectively. CONCLUSIONS AND RELEVANCE:
      These findings provide a value-based range for the cost of necitumumab from $563
      to $1309 per cycle. This study provides a framework for establishing value-based
      pricing for new oncology drugs entering the US marketplace.

PMID- 26313559
TI  - Ex vivo normothermic perfusion for quality assessment of marginal donor kidney
      transplants.
AB  - BACKGROUND: A significant proportion of kidneys procured for transplantation are
      discarded because of concerns about their suitability. In this study ex vivo
      normothermic perfusion (EVNP) was used as a quality assessment device before
      renal transplantation. METHODS: Seventy-four human kidneys deemed unsuitable for
      transplantation following retrieval underwent 60 min of EVNP with an oxygenated
      red cell-based solution at 36 degrees C. Receiver operating characteristic (ROC)
      curves were used to identify thresholds of renal blood flow and urine output.
      These thresholds and a grading of macroscopic appearance were incorporated into
      an EVNP assessment score (highest quality, 1; lowest, 5). This was applied to a
      series of 36 kidneys transplanted after EVNP. RESULTS: In the discarded kidney
      series, 60 (81 per cent) scored 1-4 and 14 (19 per cent) scored 5. Although none
      of these kidneys was transplanted, those with a score from 1 to 4 were considered
      suitable for transplantation. In the 36 transplanted kidneys, the score ranged
      between 1 and 3 (score 1, 17; score 2, 11; score 3, 8). All of these kidneys were
      transplanted without any complications or primary non-function. The delayed graft
      function rate was 6 per cent (1 of 17) in kidneys scoring 1, 0 per cent (0 of 11)
      in those scoring 2 and 38 per cent (3 of 8) in those scoring 3 (P = 0.024). The
      mean(s.d.) estimated glomerular filtration rate at 12 months was 51(16), 63(15)
      and 38(21) ml in kidneys scoring 1, 2 and 3 respectively (P = 0.015). CONCLUSION:
      EVNP combined with a simple scoring system is an innovative technology for
      pretransplant assessment of kidney quality and acceptability for transplantation.
      This study suggests that a high percentage of retrieved kidneys are being
      discarded unnecessarily.

PMID- 26313560
TI  - Do Cost Functions for Tracking Error Generalize across Tasks with Different Noise
      Levels?
AB  - Control of human-machine interfaces are well modeled by computational control
      models, which take into account the behavioral decisions people make in
      estimating task dynamics and state for a given control law. This control law is
      optimized according to a cost function, which for the sake of mathematical
      tractability is typically represented as a series of quadratic terms. Recent
      studies have found that people actually use cost functions for reaching tasks
      that are slightly different than a quadratic function, but it is unclear which of
      several cost functions best explain human behavior and if these cost functions
      generalize across tasks of similar nature but different scale. In this study, we
      used an inverse-decision-theory technique to reconstruct the cost function from
      empirical data collected on 24 able-bodied subjects controlling a myoelectric
      interface. Compared with previous studies, this experimental paradigm involved a
      different control source (myoelectric control, which has inherently large
      multiplicative noise), a different control interface (control signal was mapped
      to cursor velocity), and a different task (the tracking position dynamically
      moved on the screen throughout each trial). Several cost functions, including a
      linear-quadratic; an inverted Gaussian, and a power function, accurately
      described the behavior of subjects throughout this experiment better than a
      quadratic cost function or other explored candidate cost functions (p<0.05).
      Importantly, despite the differences in the experimental paradigm and a
      substantially larger scale of error, we found only one candidate cost function
      whose parameter was consistent with the previous studies: a power function (cost
      ? erroralpha) with a parameter value of alpha = 1.69 (1.53-1.78 interquartile
      range). This result suggests that a power-function is a representative function
      of user's error cost over a range of noise amplitudes for pointing and tracking
      tasks.

PMID- 26313561
TI  - Spatially-Distributed Cost-Effectiveness Analysis Framework to Control Phosphorus
      from Agricultural Diffuse Pollution.
AB  - Best management practices (BMPs) for agricultural diffuse pollution control are
      implemented at the field or small-watershed scale. However, the benefits of BMP
      implementation on receiving water quality at multiple spatial is an ongoing
      challenge. In this paper, we introduce an integrated approach that combines risk
      assessment (i.e., Phosphorus (P) index), model simulation techniques
      (Hydrological Simulation Program-FORTRAN), and a BMP placement tool at various
      scales to identify the optimal location for implementing multiple BMPs and
      estimate BMP effectiveness after implementation. A statistically significant
      decrease in nutrient discharge from watersheds is proposed to evaluate the
      effectiveness of BMPs, strategically targeted within watersheds. Specifically, we
      estimate two types of cost-effectiveness curves (total pollution reduction and
      proportion of watersheds improved) for four allocation approaches. Selection of a
      ''best approach" depends on the relative importance of the two types of
      effectiveness, which involves a value judgment based on the random/aggregated
      degree of BMP distribution among and within sub-watersheds. A statistical
      optimization framework is developed and evaluated in Chaohe River Watershed
      located in the northern mountain area of Beijing. Results show that BMP
      implementation significantly (p >0.001) decrease P loss from the watershed.
      Remedial strategies where BMPs were targeted to areas of high risk of P loss,
      deceased P loads compared with strategies where BMPs were randomly located across
      watersheds. Sensitivity analysis indicated that aggregated BMP placement in
      particular watershed is the most cost-effective scenario to decrease P loss. The
      optimization approach outlined in this paper is a spatially hierarchical method
      for targeting nonpoint source controls across a range of scales from field to
      farm, to watersheds, to regions. Further, model estimates showed targeting at
      multiple scales is necessary to optimize program efficiency. The integrated model
      approach described that selects and places BMPs at varying levels of
      implementation, provides a new theoretical basis and technical guidance for
      diffuse pollution management in agricultural watersheds. 

PMID- 26313563
TI  - Investigation of the effectiveness of disinfectants against planktonic and
      biofilm forms of P. aeruginosa and E. faecalis cells using a compilation of
      cultivation, microscopic and flow cytometric techniques.
AB  - This study evaluated the effectiveness of selected disinfectants against
      bacterial cells within a biofilm using flow cytometry, the conventional total
      viable count test and scanning electron microscopy (SEM). A flow cytometric
      procedure based on measurement of the cellular redox potential (CRP) was
      demonstrated to have potential for the rapid evaluation of activity against
      biofilm and planktonic forms of microbes. Quaternary ammonium compound-based
      disinfectant (QACB) demonstrated a higher level of anti-microbial activity than a
      performic acid preparation (PAP), with mean CRP values against P. aeruginosa
      cells of 2 and 1.33 relative fluorescence units (RFU) vs 63.33 and 61.33 RFU for
      8 and 24 h cultures respectively. Flow cytometric evaluation of the anti-biofilm
      activity demonstrated a higher efficacy of QACB compared to PAP for P. aeruginosa
      cells of 1 and 0.66 RFU vs 18.33 and 22.66 RFU for 8 and 24 h cultures
      respectively. SEM images of treated P. aeruginosa cells demonstrated disinfectant
      specific effects on cell morphology.

PMID- 26313562
TI  - Posttranslational regulation of polycystin-2 protein expression as a novel
      mechanism of cholangiocyte reaction and repair from biliary damage.
AB  - Polycystin-2 (PC2 or TRPPC2), a member of the transient receptor potential
      channel family, is a nonselective calcium channel. Mutations in PC2 are
      associated with polycystic liver diseases. PC2-defective cholangiocytes show
      increased production of cyclic adenosine monophosphate, protein kinase A
      dependent activation of the extracellular signal-regulated kinase 1/2 (ERK1/2)
      pathway, hypoxia-inducible factor 1alpha (HIF-1alpha)-mediated vascular
      endothelial growth factor (VEGF) production, and stimulation of cyst growth and
      progression. Activation of the ERK/HIF-1alpha/VEGF pathway in cholangiocytes
      plays a key role during repair from biliary damage. We hypothesized that PC2
      levels are modulated during biliary damage/repair, resulting in activation of the
      ERK/HIF-1alpha/VEGF pathway. PC2 protein expression, but not its gene expression,
      was significantly reduced in mouse livers with biliary damage (Mdr2(-/-)
      knockout, bile duct ligation, 3,5-diethoxycarbonyl-1,4-dihydrocollidine
      treatment). Treatment of cholangiocytes with proinflammatory cytokines, nitric
      oxide donors, and endoplasmic reticulum stressors increased ERK1/2
      phosphorylation, HIF-1alpha transcriptional activity, secretion of VEGF, and VEGF
      receptor type 2 phosphorylation and down-regulated PC2 protein expression without
      affecting PC2 gene expression. Expression of homocysteine-responsive endoplasmic
      reticulum-resident ubiquitin-like domain member 1 protein and NEK, ubiquitin-like
      proteins that promote proteosomal PC2 degradation, was increased. Pretreatment
      with the proteasome inhibitor MG-132 restored the expression of PC2 in cells
      treated with cytokines but not in cells treated with nitric oxide donors or with
      endoplasmic reticulum stressors. In these conditions, PC2 degradation was instead
      inhibited by interfering with the autophagy pathway. Treatment of 3,5
      diethoxycarbonyl-1,4-dihydrocollidine mice and of Mdr2(-/-) mice with the
      proteasome inhibitor bortezomib restored PC2 expression and significantly reduced
      the ductular reaction, fibrosis, and phosphorylated ERK1/2. CONCLUSION: In
      response to biliary damage, PC2 expression is modulated posttranslationally by
      the proteasome or the autophagy pathway, and PC2 down-regulation is associated
      with activation of ERK1/2 and an increase of HIF-1alpha-mediated VEGF secretion;
      treatments able to restore PC2 expression and to reduce ductular reaction and
      fibrosis may represent a new therapeutic approach in biliary diseases.

PMID- 26313564
TI  - Field degradation of aminopyralid and clopyralid and microbial community response
      to application in Alaskan soils.
AB  - High-latitude regions experience unique conditions that affect the degradation
      rate of agrochemicals in the environment. In the present study, data collected
      from 2 field sites in Alaska, USA (Palmer and Delta) were used to generate a
      kinetic model for aminopyralid and clopyralid degradation and to describe the
      microbial community response to herbicide exposure. Field plots were sprayed with
      herbicides and sampled over the summer of 2013. Quantification was performed via
      liquid chromatrography/tandem mass spectrometry, and microbial diversity was
      assessed via next-generation sequencing of bacterial 16S ribosomal ribonucleic
      acid (rRNA) genes. Both compounds degraded rapidly via pseudo-first-order
      degradation kinetics between 0 d and 28 d (t1/2  = 9.1-23.0 d), and then
      degradation slowed thereafter through 90 d. Aminopyralid concentration was 0.048
      MUg/g to 0.120 MUg/g at 90 d post application, whereas clopyralid degraded
      rapidly at the Palmer site but was recovered in Delta soil at a concentraction of
      0.046 MUg/g. Microbial community diversity was moderately impacted by herbicide
      treatment, with the effect more pronounced at Delta. These data predict
      reductions in crop yield when sensitive plants (potatoes, tomatoes, marigolds,
      etc.) are rotated onto treated fields. Agricultural operations in high-latitude
      regions, both commercial and residential, rely heavily on cultivation of such
      crops and care must be taken when rotating.

PMID- 26313565
TI  - Highly Sensitive Electro-Plasmonic Switches Based on Fivefold Stellate Polyhedral
      Gold Nanoparticles.
AB  - Electron-photon coupling in metal nanostructures has raised a new trend for
      active plasmonic switch devices in both fundamental understanding and
      technological applications. However, low sensitivity switches with an on/off
      ratio less than 5 have restricted applications. In this work, an electrically
      modulated plasmonic switch based on a surface-enhanced Raman spectroscopy (SERS)
      system with a single fivefold stellate polyhedral gold nanoparticle (FSPAuNP) is
      reported. The reversible switch of the SERS signal shows high sensitivity with an
      on/off ratio larger than 30. Such a high on/off ratio arises primarily from the
      plasmonic resonance shift of the FSPAuNP with the incident laser due to the
      altered free electron density on the nanoparticle under an applied
      electrochemical potential. This highly sensitive electro-plasmonic switch may
      enable further development of plasmonic devices. 

PMID- 26313566
TI  - Gender-specific association between night-work exposure and type-2 diabetes:
      results from longitudinal study of adult health, ELSA-Brasil.
AB  - OBJECTIVES: Diabetes is a multifactorial disease of increasing prevalence. The
      literature suggests an impact of night work on metabolic components, though the
      relationship with diabetes is unclear. Our aim was to investigate gender-specific
      associations between night work and type-2 diabetes (DM2) or impaired glucose
      tolerance (IGT) using baseline data of the Brazilian Longitudinal Study of Adult
      Health (ELSA-Brasil). METHODS: The cohort comprised 15 105 civil servants, aged
      35-74 years. Baseline assessments (2008-2010) included clinical and laboratory
      measurements and interviews on sociodemographic, occupational, and health
      characteristics. RESULTS: In the baseline sample (N=14 427), 19.6% were
      classified as having DM2 and 20.5% as having IGT. Mean age was 52.1 (SD 9.1)
      years. A total of 2041 participants worked at night for 1-20 years and 687 for
      >20 years. Among women exposed to night work for >20 years compared with no night
      work after adjustments for potential confounders, including obesity, the odds
      ratios (OR) derived from multinomial logistic regression for DM2 and IGT were
      1.42 [95% confidence interval (95% CI) 1.39-1.45] and 0.96 (95% CI 0.94-0.99),
      respectively. Among men exposed to night work for >20 years compared with no
      night work, the OR for DM2 and IGT were 1.06 (95% CI 1.04-1.08) and 0.99 (95% CI
      0.98-1.01), respectively. CONCLUSIONS: The association between years of night
      work and diabetes is stronger among women than men. Longitudinal studies from
      ELSA-Brasil will be able to corroborate or refute these findings.

PMID- 26313567
TI  - Active Transportation Surveillance - United States, 1999-2012.
AB  - PROBLEM/CONDITION: Physical activity is a health-enhancing behavior, and most
      U.S. adults do not meet the 2008 Physical Activity Guidelines for Americans.
      Active transportation, such as by walking or bicycling, is one way that persons
      can be physically active. No comprehensive, multiyear assessments of active
      transportation surveillance in the United States have been conducted. PERIOD
      COVERED: 1999-2012. DESCRIPTION OF SYSTEMS: Five surveillance systems assess one
      or more components of active transportation. The American Community Survey and
      the National Household Travel Survey (NHTS) both assess the mode of
      transportation to work in the past week. From these systems, the proportion of
      respondents who reported walking or bicycling to work can be calculated. NHTS and
      the American Time Use Survey include 1-day assessments of trips or activities.
      With that information, the proportion of respondents who report any walking or
      bicycling for transportation can be calculated. The National Health and Nutrition
      Examination Survey and the National Health Interview Survey both assess recent
      (i.e., in the past week or past month) habitual physical activity behaviors,
      including those performed during active travel. From these systems, the
      proportion of respondents who report any recent habitual active transportation
      can be calculated. RESULTS: The prevalence of active transportation as the
      primary commute mode to work in the past week ranged from 2.6% to 3.4%. The 1-day
      assessment indicated that the prevalence of any active transportation ranged from
      10.5% to 18.5%. The prevalence of any habitual active transportation ranged from
      23.9% to 31.4%. No consistent trends in active transportation across time periods
      and surveillance systems were identified. Among systems, active transportation
      was usually more common among men, younger respondents, and minority
      racial/ethnic groups. Among education groups, the highest prevalence of active
      transportation was usually among the least or most educated groups, and active
      transportation tended to be more prevalent in densely populated, urban areas.
      INTERPRETATION: Active transportation is assessed in a wide variety of ways in
      multiple surveillance systems. Different assessment techniques and construct
      definitions result in widely discrepant estimates of active transportation;
      however, some consistent patterns were detected across covariates. Although each
      type of assessment (i.e., transportation to work, single day, and habitual
      behavior) measures a different active transportation component, all can be used
      to monitor population trends in active transportation participation. PUBLIC
      HEALTH ACTION: An understanding of the strengths, limitations, and lack of
      comparability of active transportation assessment techniques is necessary to
      correctly evaluate findings from the various surveillance systems. When used
      appropriately, these systems can be used by public health and transportation
      professionals to monitor population participation in active transportation and
      plan and evaluate interventions that influence active transportation.

PMID- 26313568
TI  - Borrelial Lymphocytoma in Children.
AB  - BACKGROUND: The aim of this study was to investigate demographic features,
      clinical characteristics, laboratory findings and posttreatment course of the
      disease in children with borrelial lymphocytoma (BL). METHODS: Between 2008 and
      2014, we prospectively studied 33 children younger than 15 years with untreated
      BL. Data on demographic and clinical features were collected by means of a
      questionnaire. Serological testing and Lyme borrelia blood cultures were
      performed. All patients were treated with recommended antibiotics. Patients were
      followed up at least 3 months after inclusion into the study. RESULTS: Twenty-two
      boys and 11 girls, aged 2-13 (median, 5.5) years, fulfilled the inclusion
      criteria. A tick bite at the site of BL was recalled by 30%. The median
      incubation period was 10.5 (range, 1-38) days. The median duration of BL before
      the initial examination was 10 (range, 0-270) days. In 88% of patients, BL was
      localized on ear lobe. The color/shape of BL was more often red (73%) and puffy
      (91%). Median size was 1.5 (range, 0.5-3) cm. The initial disease was mild in
      82%. Associated symptoms were reported in 36% of patients. Concomitant solitary
      erythema migrans and meningitis were detected in 9% and 3% of patients,
      respectively. Serum borrelial antibodies were present in 40% of patients. In 7%,
      Borrelia afzelii was isolated from blood. Posttreatment course of the disease
      revealed the median duration of BL and systemic symptoms for 16 (range, 2-46) and
      15 (range, 3-40) days, respectively. CONCLUSIONS: BL in children, treated with
      recommended antibiotics, is a mild disease with a good prognosis.

PMID- 26313569
TI  - Anti-NMDA Receptor Encephalitis in the Polar Bear (Ursus maritimus) Knut.
AB  - Knut the polar bear of the Berlin Zoological Garden drowned in 2011 following
      seizures and was diagnosed as having suffered encephalitis of unknown etiology
      after exhaustive pathogen screening. Using the diagnostic criteria applied to
      human patients, we demonstrate that Knut's encephalitis is almost identical to
      anti-NMDA receptor encephalitis which is a severe autoimmune disease representing
      the most common non-infectious encephalitis in humans. High concentrations of
      antibodies specific against the NR1 subunit of the NMDA receptor were detected in
      Knut's cerebrospinal fluid. Histological examination demonstrated very similar
      patterns of plasma cell infiltration and minimal neuronal loss in affected brain
      areas. We conclude that Knut suffered anti-NMDA receptor encephalitis making his
      the first reported non-human case of this treatable disease. The results suggest
      that anti-NMDA receptor encephalitis may be a disease of broad relevance to
      mammals that until now has remained undiagnosed. 

PMID- 26313570
TI  - Bicoronal frontobasal approach with a limited, midline orbital bar osteotomy - a
      technical note.
AB  - The frontobasal approach remains a workhorse for removing large olfactory groove
      meningiomas. Removal of the orbital bar in addition to standard bifrontal
      craniotomy allows for additional basal exposure, minimising brain retraction and
      allowing early and direct access to both the vascular supply and dural origin of
      this tumour. Here, we describe a simple yet effective modification to the
      standard orbital bar osteotomy. It has the benefit of being simpler and faster
      with improved cosmesis compared with an osteotomy of the entire orbital bar. It
      also has the advantage of not requiring manipulation of the supraorbital nerves
      or intraorbital or periorbital dissection. 

PMID- 26313571
TI  - Transcriptomic Analysis and Meta-Analysis of Human Granulosa and Cumulus Cells.
AB  - Specific gene expression in oocytes and its surrounding cumulus (CC) and
      granulosa (GC) cells is needed for successful folliculogenesis and oocyte
      maturation. The aim of the present study was to compare genome-wide gene
      expression and biological functions of human GC and CC. Individual GC and CC were
      derived from 37 women undergoing IVF procedures. Gene expression analysis was
      performed using microarrays, followed by a meta-analysis. Results were validated
      using quantitative real-time PCR. There were 6029 differentially expressed genes
      (q < 10-4); of which 650 genes had a log2 FC >= 2. After the meta-analysis there
      were 3156 genes differentially expressed. Among these there were genes that have
      previously not been reported in human somatic follicular cells, like prokineticin
      2 (PROK2), higher expressed in GC, and pregnancy up-regulated nonubiquitous CaM
      kinase (PNCK), higher expressed in CC. Pathways like inflammatory response and
      angiogenesis were enriched in GC, whereas in CC, cell differentiation and
      multicellular organismal development were among enriched pathways. In conclusion,
      transcriptomes of GC and CC as well as biological functions, are distinctive for
      each cell subpopulation. By describing novel genes like PROK2 and PNCK, expressed
      in GC and CC, we upgraded the existing data on human follicular biology. 

PMID- 26313572
TI  - Expression of Flotilin-2 and Acrosome Biogenesis Are Regulated by MiR-124 during
      Spermatogenesis.
AB  - MicroRNAs (miRNAs) are a class of short non-coding RNA molecules, which diversely
      regulate gene expression in organisms. Although the regulatory role of these
      small RNA molecules has been recently explored in animal spermatogenesis, the
      role of miR-124 in male germ cells is poorly defined. In our previous study,
      flotillin-2 was investigated as a novel Golgi-related protein involved in sperm
      acrosome biogenesis. The current study was designed to analyze the contribution
      of miR-124 in the regulation of flotillin-2 expression during mouse acrosome
      biogenesis. Luciferase assays revealed the target effects of miR-124 on flotillin
      2 expression. Following intratesticular injection of miR-124 in 3-week-old male
      mice, quantitative real-time RT-PCR and western blot analysis were employed to
      confirm the function of miR-124 in regulating flotillin-2 after 48 hours. Sperm
      abnormalities were assessed 3 weeks later by ordinary optical microscopy, the
      acrosome abnormalities were also assessed by PNA staining and transmission
      electron microscopy. The results showed the proportion of sperm acrosome
      abnormalities was significantly higher than that of the control group. The
      expression of flotillin-2 and caveolin-1 was significantly downregulated during
      acrosome biogenesis. These results indicated that miR-124 could potentially play
      a role in caveolin-independent vesicle trafficking and modulation of flotillin-2
      expression in mouse acrosome biogenesis. 

PMID- 26313573
TI  - Maturation and Sex Differences in Neuromuscular Characteristics of Youth
      Athletes.
AB  - Understanding how neuromuscular factors that are associated with lower extremity
      injury risk, such as landing kinematics, muscle strength, and flexibility, change
      as children mature may enhance age-specific recommendations for injury prevention
      programs. The purpose of this study was to compare these factors in prepubertal,
      pubertal, and postpubertal male and female athletes. Subjects were classified on
      maturation stage (prepubertal: 16 males, 15 females, age: 9 +/- 1 years;
      pubertal: 13 males, 12 females, age: 12 +/- 3 years; postpubertal: 30 males, 27
      females, age: 16 +/- 2 years). Researchers measured lower extremity isometric
      muscle strength and flexibility and evaluated kinematics and vertical ground
      reaction forces (VGRFs) during a jump-landing task. Three-dimensional kinematics
      at initial contact (IC), joint displacements, and peak VGRF were calculated.
      Separate multivariate analyses of variance were performed to evaluate sex and
      maturation differences (alpha <= 0.05). Postpubertal females landed with less
      knee flexion at IC (p = 0.006) and demonstrated lower knee extension strength (p
      = 0.01) than prepubertal and pubertal females. Postpubertal males landed with
      less hip adduction displacement (postpubertal males = 12.53 +/- 6.15 degrees ,
      prepubertal males = 18.84 +/- 7.47 degrees ; p = 0.04) and less peak VGRF
      (postpubertal males = 1.53 +/- 0.27% body weight [BW], prepubertal males = 1.99
      +/- 0.32% BW; p = 0.03) compared with prepubertal males. These findings suggest
      encouraging sagittal plane absorption and decreasing frontal plane motion at the
      hip, whereas maintaining quadriceps strength may be important for reducing injury
      risk in postpubertal athletes.

PMID- 26313574
TI  - Changes in Body Composition in Division I Football Players Over a Competitive
      Season and Recovery in Off-Season.
AB  - This study investigated changes in body composition over 1 competitive football
      season in D-I collegiate football players (N = 53; by position, 21 linemen vs. 32
      nonline; or by seniority, 30 upperclassmen vs. 23 underclassmen) and additional
      changes by the following spring season (N = 46; 20 linemen vs. 26 nonline; 27
      upperclassmen vs. 19 underclassmen). Body composition by dual-energy x-ray
      absorptiometry (DXA) was completed pre- and post-season and the following spring.
      For the team as a whole, player weight decreased 1.3 kg (1.2%) and lean mass
      decreased 1.4 kg (1.6%) over the season. Absolute fat mass showed no change;
      however, percent body fat showed a 0.5% increase. There was an interaction
      between player position and seniority for changes in lean mass (p < 0.01). In
      nonline positions upperclassmen lost more lean mass than underclassmen, whereas
      in line positions underclassmen lost more lean mass than upperclassmen. Spring
      measures indicate that weight did not increase during the off-season, but
      improvement in body composition was noted. Lean mass increased by 2.2 kg (2.6%),
      whereas absolute fat mass decreased by 1.4 kg (6.7%). Although weight and lean
      mass losses during the competitive season were recovered in the off-season,
      changes in collegiate football programs that include nutrition counseling,
      dietary recommendations, monitoring of weight, and skin-fold testing as an
      estimate of body fat change would be beneficial to players. Strength and
      conditioning coaches and staff need to consider strategies to incorporate these
      practices into their programs.

PMID- 26313575
TI  - Association Between Vitamin D Status and Maximal-Intensity Exercise Performance
      in Junior and Collegiate Hockey Players.
AB  - Recent evidence suggests that athletes are at risk for poor vitamin D status.
      This study used a cross-sectional design to investigate the strength of
      association between 25-hydroxyvitamin D (25(OH)D) concentration and measures of
      maximal-intensity exercise performance in competitive hockey players. Fifty-three
      collegiate and junior male ice hockey players training near Minneapolis, MN (44.9
      degrees  N latitude) participated in the study during the off-season (May 16-June
      28). Circulating 25(OH)D concentration, grip strength, vertical jump performance,
      and power production during the Wingate Anaerobic Test (WAnT) were evaluated.
      Despite no athletes with 25(OH)D concentration indicative of deficiency (<20
      ng.mL), positive bivariate correlations were detected between vitamin D status,
      relative grip strength (p = 0.024), and peak power during the WAnT (p = 0.035).
      Only for relative grip strength (p = 0.043), did 25(OH)D concentration predict
      performance after adjusting for level of play, fat-free mass, fat mass, and self
      reported total physical activity in sequential linear regression. Vitamin D
      status was positively associated with starting gradient (p = 0.020) during the
      squat jump, with higher concentrations associated with increased rate of force
      development in the initial portion of the jump. Interventional trials should
      investigate the impact of vitamin D supplementation on maximal-intensity exercise
      performance outcomes and rate of force development in large samples of vitamin D
      deficient athletes while controlling for training exposure. Our data indicate
      that if vitamin D status is causally related to maximal-intensity exercise
      performance in athletes, the effect size is likely small.

PMID- 26313576
TI  - Physiological and Fatigue Responses Associated With Male and Mixed-Gender
      Ultimate Frisbee Game Play.
AB  - The aims of this study were to describe the physiological and fatigue responses
      associated with indoor Ultimate Frisbee game play, compare exercise intensities
      attained to current activity guidelines, and compare responses between male and
      mixed-gender game formats. A between-subjects (game format) repeated-measures
      (time points) observational experimental design was used. Subjects competed in
      male (n = 10; age: 26.3 +/- 7.6 years) or mixed-gender (males: n = 4; 28.5 +/-
      5.7 years; females: n = 6; 28.3 +/- 8.1 years) indoor Ultimate Frisbee game play.
      Games consisted of 10-minute halves, with heart rate (HR), blood lactate
      concentration ([BLa]), rating of perceived exertion, and 5-m and 20-m sprint
      times measured. Durations spent in HR-derived intensity zones and sprint
      decrements were calculated across games. Mixed-gender game play produced
      significantly (p <= 0.05) higher relative HR (94.3 +/- 5.1% vs. 89.6 +/- 4.8%
      HRmax) and [BLa] (8.31 +/- 2.22 mmol.L vs. 4.68 +/- 1.89 mmol.L) than male game
      play. Significantly (p <= 0.05) longer durations were spent at vigorous (male:
      60.2 +/- 26.1%; mixed-gender: 36.8 +/- 34.8%) and near-maximal (male: 31.6 +/-
      27.6%; mixed-gender: 58.6 +/- 37.7%) exercise intensities than moderate (3.9
      7.2%), light (0.7-1.0%), and very light (0-0.1%) intensities in both formats.
      Limited physiological and sprint fatigue was apparent across games. Subjects
      primarily performed at vigorous and near-maximal intensities during Ultimate
      Frisbee. The greater physiological demands encountered during mixed-gender game
      play might be attributed to underlying gender-mediated cardiovascular
      differences. These findings support the efficacy of Ultimate Frisbee as a
      prescriptive exercise tool for health benefit.

PMID- 26313577
TI  - The Effect of Rocktape on Rating of Perceived Exertion and Cycling Efficiency.
AB  - The purpose of this study was to investigate the effects of Rocktape (RT), a type
      of kinesiology tape, on perceived exertion and cycling efficiency. Eighteen
      recreational cyclists volunteered as subjects for this study. Four experimental
      conditions were used: (a) 60% VO2peak with RT, (b) 60% VO2peak without RT, (c)
      80% VO2peak with RT, and (d) 80% VO2peak without RT. The Borg rating of perceived
      exertion (RPE) scale was used to evaluate subjective exertion during the cycling
      bouts. Overall RPE and leg, arm, and chest RPEs were obtained (RPE-O, RPE-L, RPE
      A, and RPE-C, respectively). Gross cycling efficiency was determined by
      calculating the ratio of the amount of work performed to the energy expended.
      Repeated-measures analysis of variance was used to investigate the differences
      between the 2 intensities and 2 tape conditions. There were main effects of
      intensity (p < 0.001) and tape (p = 0.02) found for the RPE-O, with RPE-C showing
      similar results for intensity (p < 0.001) and tape (p = 0.02). Similar findings
      were present for the RPE-C, and main effects of intensity (p < 0.001) and tape (p
      = 0.02) were discovered. A significant main effect of intensity was found for
      efficiency (p = 0.03), with the 80% intensity condition showing a greater level
      of efficiency than the 60% intensity condition. However, the use of RT did not
      increase gross efficiency (p = 0.61). The main finding in this study was that
      subjects reported a lower level of exertion overall and at the chest, which may
      lead to increases in overall performance of these athletes. The use of RT before
      athletic events should not be discouraged.

PMID- 26313578
TI  - Kinematics of Faster Acceleration Performance of the Quick Single in Experienced
      Cricketers.
AB  - The introduction of the shorter match formats for cricket (i.e., Twenty20)
      requires batsmen to be proficient in sprint acceleration to increase run scoring
      potential. Therefore, the study aim was to identify the kinematics of faster
      acceleration performance of nonstriking batsmen when completing a quick single.
      Eighteen experienced male cricketers currently playing cricket in a regional
      competition in Australia completed 17.68-m sprints using a match-specific start
      (walking start, bat dragged through crease, leg guards worn). Timing gates
      recorded the 0-5 and 0-17.68 m time. Joint and step kinematics were analyzed
      through the first and second steps through 3-dimensional motion analysis.
      Subjects were split into faster and slower groups according to 0- to 5-m time,
      and a 1-way analysis of variance determined significant (p <= 0.05) between-group
      differences. Effect sizes and Pearson's correlations (r) were also calculated.
      The faster group was significantly quicker for the 0-5 and 0-17.68 m intervals
      and had a 10% longer first, and 11% longer second, step. Second step swing leg
      hip adduction was 23% greater in the faster group. A significant negative
      correlation (r = -0.647) was found between second step drive leg extension and 0-
      to 5-m time. Batsmen should cover the initial 5 m of a quick single in the
      shortest time possible to increase the likelihood of a successful run. This is
      aided by longer first and second steps and increased hip adduction to transition
      into normal sprint technique. Step length development should be a key
      consideration for coaches attempting to improve quick single performance.

PMID- 26313579
TI  - Variability in Laboratory vs. Field Testing of Peak Power, Torque, and Time of
      Peak Power Production Among Elite Bicycle Motocross Cyclists.
AB  - The aim of this study was to ascertain the variation in elite male bicycle
      motocross (BMX) cyclists' peak power, torque, and time of power production during
      laboratory and field-based testing. Eight elite male BMX riders volunteered for
      the study, and each rider completed 3 maximal sprints using both a Schoberer Rad
      Messtechnik (SRM) ergometer in the laboratory and a portable SRM power meter on
      an Olympic standard indoor BMX track. The results revealed a significantly higher
      peak power (p <= 0.001, 34 +/- 9%) and reduced time of power production (p <=
      0.001, 105 +/- 24%) in the field tests when compared with laboratory-derived
      values. Torque was also reported to be lower in the laboratory tests but not to
      an accepted level of significance (p = 0.182, 6 +/- 8%). These results suggest
      that field-based testing may be a more effective and accurate measure of a BMX
      rider's peak power, torque, and time of power production.

PMID- 26313580
TI  - Agreement Between Face-to-Face and Free Software Video Analysis for Assessing
      Hamstring Flexibility in Adolescents.
AB  - The objective of this study was to determine the level of agreement between face
      to-face hamstring flexibility measurements and free software video analysis in
      adolescents. Reduced hamstring flexibility is common in adolescents (75% of boys
      and 35% of girls aged 10). The length of the hamstring muscle has an important
      role in both the effectiveness and the efficiency of basic human movements, and
      reduced hamstring flexibility is related to various musculoskeletal conditions.
      There are various approaches to measuring hamstring flexibility with high
      reliability; the most commonly used approaches in the scientific literature are
      the sit-and-reach test, hip joint angle (HJA), and active knee extension. The
      assessment of hamstring flexibility using video analysis could help with
      adolescent flexibility follow-up. Fifty-four adolescents from a local school
      participated in a descriptive study of repeated measures using a crossover
      design. Active knee extension and HJA were measured with an inclinometer and were
      simultaneously recorded with a video camera. Each video was downloaded to a
      computer and subsequently analyzed using Kinovea 0.8.15, a free software
      application for movement analysis. All outcome measures showed reliability
      estimates with alpha > 0.90. The lowest reliability was obtained for HJA (alpha =
      0.91). The preliminary findings support the use of a free software tool for
      assessing hamstring flexibility, offering health professionals a useful tool for
      adolescent flexibility follow-up.

PMID- 26313581
TI  - Biplanar Contour-Oriented Approach to Lower Eyelid and Midface Rejuvenation.
AB  - IMPORTANCE: Cosmetic rejuvenation of the lower eyelid-midface complex has evolved
      as our understanding of 3-dimensional midfacial aging and anatomy has become more
      sophisticated. Treating the lower eyelid and the midface as a single aesthetic
      unit leads to a more effective and natural-appearing rejuvenation. OBSERVATIONS:
      This is a review of midfacial anatomy and a 5-step approach to lower
      blepharoplasty and midface rejuvenation: (1) midfacial autologous fat transfer,
      (2) canthoplasty, (3) transconjunctival orbicularis-retaining ligament release
      and orbital fat manipulation, (4) transcutaneous midface-superficial muscular
      aponeurotic system elevation and orbicularis contouring, and (5) skin treatment.
      In addition, long-term aesthetic outcomes and complications are reviewed for 43
      patients (86 eyelids) who underwent the 5-step biplanar approach lower
      blepharoplasty and midfacial rejuvenation (40 women and 3 men, with a mean age of
      60 years). Follow-up averaged 10.8 months. Forty-one patients rated their outcome
      as "excellent," and 3 patients rated their outcome as "good." No patients rated
      their outcome as "fair," "no improvement," or "worsening." Seven patients (7
      eyelids) had unilateral complications requiring postoperative intervention.
      CONCLUSIONS AND RELEVANCE: The biplanar contour-oriented approach to lower
      blepharoplasty and midfacial rejuvenation is an option for treatment for aging of
      the lower eyelid-midface complex. The aesthetic outcomes appear natural owing to
      the synergy of reconstructing the aging changes of multiple lower eyelid and
      midface structures.

PMID- 26313582
TI  - Introducing an enhanced recovery programme to an established totally
      intracorporeal robot-assisted radical cystectomy service.
AB  - OBJECTIVE: The aim of this study was to assess the effect of introducing an
      enhanced recovery programme (ERP) to an established robot-assisted radical
      cystectomy (RARC) service. MATERIALS AND METHODS: Data were prospectively
      collected on 221 consecutive patients undergoing totally intracorporeal RARC
      between December 2003 and May 2014. The ERP was specifically designed to support
      an evolving RARC service, where increasing proportions of patients requiring
      radical cystectomy underwent RARC. Patient demographics and outcomes before and
      after implementation of the ERP were compared. The primary endpoint was length of
      stay (LOS). Secondary outcomes included age, American Society of
      Anesthesiologists (ASA) score, preoperative staging, operative time,
      complications and readmissions. Differences in outcomes between patients before
      and after implementation of ERP were tested with the Jonckheere-Terpstra trend
      test and quantile regression with backward selection. RESULTS: Following
      implementation of the ERP, the demographics of the patients (n = 135) changed,
      with median age increasing from 66 to 70 years (p < 0.01), higher ASA grade (p <
      0.001), higher preoperative stage cancer (pT >= 2, p < 0.05) and increased
      likelihood of undergoing an ileal conduit diversion (p < 0.001). Median LOS
      before ERP was 9 days [interquartile range (IQR) 8-13 days] and after ERP was 8
      days (IQR 6-10 days) (p < 0.001). ASA grade and neoadjuvant chemotherapy also
      affected LOS (p < 0.05 and p < 0.01, respectively). There was no significant
      difference in 30 day complication rates, readmission rates or 90 day mortality,
      with 59% experiencing complications before ERP implementation and 57% after
      implementation. The majority of complications were low grade. CONCLUSIONS:
      Patient demographics changed as the RARC service evolved from selected patients
      to a general service. Despite worsening demographics, LOS decreased following ERP
      implementation. This evidence-based ERP safely standardized perioperative care,
      resulting in decreased LOS and decreased variability in LOS.

PMID- 26313584
TI  - Measurement of 238U and 232Th in Petrol, Gas-oil and Lubricant Samples by Using
      Nuclear Track Detectors and Resulting Radiation Doses to the Skin of Mechanic
      Workers.
AB  - Workers in repair shops of vehicles (cars, buses, truck, etc.) clean carburetors,
      check fuel distribution, and perform oil changes and greasing. To explore the
      exposure pathway of (238)U and (232)Th and its decay products to the skin of
      mechanic workers, these radionuclides were measured inside petrol, gas-oil, and
      lubricant material samples by means of CR-39 and LR-115 type II solid state
      nuclear track detectors (SSNTDs), and corresponding annual committed equivalent
      doses to skin were determined. The maximum total equivalent effective dose to
      skin due to the (238)U and (232)Th series from the application of different
      petrol, gas-oil, and lubricant samples by mechanic workers was found equal to 1.2
      mSv y(-1) cm(-2).

PMID- 26313585
TI  - Compact Tissue-equivalent Proportional Counter for Deep Space Human Missions.
AB  - Effects on human health from the complex radiation environment in deep space have
      not been measured and can only be simulated here on Earth using experimental
      systems and beams of radiations produced by accelerators, usually one beam at a
      time. This makes it particularly important to develop instruments that can be
      used on deep-space missions to measure quantities that are known to be relatable
      to the biological effectiveness of space radiation. Tissue-equivalent
      proportional counters (TEPCs) are such instruments. Unfortunately, present TEPCs
      are too large and power intensive to be used beyond low Earth orbit (LEO). Here,
      the authors describe a prototype of a compact TEPC designed for deep space
      applications with the capability to detect both ambient galactic cosmic rays and
      intense solar particle event radiation. The device employs an approach that
      permits real-time determination of yD (and thus quality factor) using a single
      detector. This was accomplished by assigning sequential sampling intervals as
      detectors "1" and "2" and requiring the intervals to be brief compared to the
      change in dose rate. Tests with g rays show that the prototype instrument
      maintains linear response over the wide dose-rate range expected in space with an
      accuracy of better than 5% for dose rates above 3 mGy h(-1). Measurements of yD
      for 200 MeV n(-1) carbon ions were better than 10%. Limited tests with fission
      spectrum neutrons show absorbed dose-rate accuracy better than 15%.

PMID- 26313583
TI  - Right-to-try laws and individual patient "compassionate use" of experimental
      oncology medications: A call for improved provider-patient communication.
AB  - The U.S. Food and Drug Administration's Expanded Access program allows patients
      with life-threatening diagnoses, such as advanced cancer, to use experimental
      medications without participating in clinical research (colloquially,
      "Compassionate Use"). Sixteen U.S. states recently passed "right-to-try"
      legislation aimed at promoting Expanded Access. Acknowledging popular support,
      Expanded Access could undermine clinical trials that benefit public health.
      Moreover, existing norms in oncologic care, for example, often lead patients to
      pursue intense treatments near the end of life, at the expense of palliation, and
      improved communication about the risks and benefits of Expanded Access would more
      often discourage its use. 

PMID- 26313586
TI  - Simulated Response of a Tissue-equivalent Proportional Counter on the Surface of
      Mars.
AB  - Uncertainties persist regarding the assessment of the carcinogenic risk
      associated with galactic cosmic ray (GCR) exposure during a mission to Mars. The
      GCR spectrum peaks in the range of 300(-1) MeV n to 700 MeV n(-1) and is
      comprised of elemental ions from H to Ni. While Fe ions represent only 0.03% of
      the GCR spectrum in terms of particle abundance, they are responsible for nearly
      30% of the dose equivalent in free space. Because of this, radiation biology
      studies focusing on understanding the biological effects of GCR exposure
      generally use Fe ions. Acting as a thin shield, the Martian atmosphere alters the
      GCR spectrum in a manner that significantly reduces the importance of Fe ions.
      Additionally, albedo particles emanating from the regolith complicate the
      radiation environment. The present study uses the Monte Carlo code FLUKA to
      simulate the response of a tissue-equivalent proportional counter on the surface
      of Mars to produce dosimetry quantities and microdosimetry distributions. The
      dose equivalent rate on the surface of Mars was found to be 0.18 Sv y(-1) with an
      average quality factor of 2.9 and a dose mean lineal energy of 18.4 keV MUm(-1).
      Additionally, albedo neutrons were found to account for 25% of the dose
      equivalent. It is anticipated that these data will provide relevant starting
      points for use in future risk assessment and mission planning studies.

PMID- 26313587
TI  - Dosimetry Support of the Ukrainian-American Case-control Study of Leukemia and
      Related Disorders Among Chornobyl Cleanup Workers.
AB  - This paper describes dose reconstruction for a joint Ukrainian-American case
      control study of leukemia that was conducted in a cohort of 110,645 male
      Ukrainian cleanup workers of the Chornobyl (Chernobyl) accident who were exposed
      to various radiation doses over the 1986-1990 time period. Individual bone-marrow
      doses due to external irradiation along with respective uncertainty distributions
      were calculated for 1,000 study subjects using the RADRUE method, which employed
      personal cleanup history data collected in the course of an interview with the
      subject himself if he was alive or with two proxies if he was deceased. The
      central estimates of the bone-marrow dose distributions range from 3.7 * 10(-5)
      to 3,260 mGy, with an arithmetic mean of 92 mGy. The uncertainties in the
      individual stochastic dose estimates can be approximated by lognormal
      distributions; the average geometric standard deviation is 2.0.

PMID- 26313588
TI  - Developing a Methodology for Determination of Elemental Composition of Shielding
      Materials.
AB  - Radiation transport simulation models can provide estimations of radiation
      effects such as detector response and detection capabilities. The objective of
      this research was to develop a methodology for quick, efficient, and effective
      determination of the composition of shielding materials to be used in radiation
      transport models. A C++ code, MatFit, was developed that used the concept of
      densitometry and the iterative method developed for the Spectrum Analysis by
      Neutron Detectors II (SAND II) computer program to estimate the elemental
      composition of shielding materials. These results were compared to previous
      neutron activation analysis (NAA) on the same samples. It was determined that
      densitometry provided an elemental approximation that yielded an attenuation rate
      within 10% of that found through NAA but requires much fewer resources, as well
      as less time. From this research, it is recommended that the developed method and
      C++ program be used when constructing models for detector response. 

PMID- 26313589
TI  - Proposed Modification to the Plutonium Systemic Model.
AB  - The currently accepted biokinetic model for plutonium distribution within the
      human body was recommended by the International Commission on Radiological
      Protection in publication 67. This model was developed from human and animal
      studies and behavioral knowledge acquired from other known bone-seeking
      radionuclides. The biokinetic model provides a mathematical means of predicting
      the distribution, retention, and clearance of plutonium within the human body
      that may be used in deriving organ, tissue, and whole body dose. This work
      proposed a modification to the ICRP 67 systemic model for plutonium that
      incorporated the latest knowledge acquired from recent human injection studies
      with physiologically based improvements. In summary, the changes included a
      separation of the liver compartments, removed the intermediate soft tissue-to
      bladder pathway, and added pathways from the blood compartment to both the
      cortical and trabecular bone volumes. The proposed model provided improved
      predictions for several bioassay indicators compared to the ICRP 67 model while
      also maintaining its basic structure. Additionally, the proposed model
      incorporated physiologically based improvements for the liver and skeleton and
      continued to ensure efficient coupling with intake biokinetic models. 

PMID- 26313590
TI  - Absorbed Dose Rates in Tissue from Prompt Gamma Emissions from Near-thermal
      Neutron Absorption.
AB  - Prompt gamma emission data from the International Atomic Energy Agency's Prompt
      Gamma-ray Neutron Activation Analysis database are analyzed to determine the
      absorbed dose rates in tissue to be expected when natural elements are exposed in
      a near-thermal neutron environment. 

PMID- 26313591
TI  - A Simple Method for Human Whole Blood Microcultures and Its Application in
      Radiation Biodosimetry.
AB  - The scoring of the cytokinesis-block micronucleus and dicentric chromosomes in
      human peripheral blood lymphocytes is used as a dosimeter of radiation exposure.
      A detailed methodology is presented for human whole blood microculture for
      cytogenetic analysis. The technique described yields more than sufficient numbers
      of mitotic lymphocytes for analyzing micronuclei and chromosome aberrations
      following exposure to radiation. 

PMID- 26313592
TI  - On Dose Reconstruction for the Million Worker Study: Status and Guidelines.

PMID- 26313596
TI  - Frequency of asthma education in primary care in the years 2007-2010.
AB  - OBJECTIVE: Recent research suggests that health disparities persist among
      asthmatic patients and receipt of asthma education, though recent guidelines have
      highlighted the importance of receiving asthma education. The purpose of this
      study was to identify trends in the receipt of asthma education as well as to
      identify disparities in asthma education using the most recently available data
      in National Ambulatory Medical Care Survey, 2007-2010. METHODS: Weighted chi
      square tests were conducted to identify associations between asthma education and
      variables of interest. A weighted multivariate logistic regression model was
      subsequently constructed to jointly assess the association of factors of interest
      on receipt of asthma education. Submission to the Campbell University
      Institutional Review Board resulted in expedited approval. RESULTS: The
      percentage of patients who receive asthma education remains quite low. After
      adjusting for all variables of interest: no statistically significant difference
      in receipt of asthma education between year groups (2007-2008, 2009-2010) was
      found (odds ratio [OR] 0.84, 95% confidence interval [CI] 0.52-1.34); patients
      seen by pediatricians (vs. internal medicine physicians) and Hispanic or Latino
      patients (vs. non-Hispanic or Latino patients) were more likely to receive asthma
      education (OR 2.72, 95% CI 1.11-6.66 and OR 2.33, 95% CI 1.18-4.60,
      respectively); and patients not prescribed a controller medication were less
      likely to receive asthma education than those who were (OR 0.56, 95% CI 0.37
      0.82). CONCLUSIONS: Combined with previously published results, it appears the
      provision of asthma education continues to be low, despite proven benefits.
      Additionally, some patient and physician characteristics may be associated with
      the delivery of asthma education.

PMID- 26313598
TI  - Understanding Emergent Dynamics: Using a Collective Activity Coordinate of a
      Neural Network to Recognize Time-Varying Patterns.
AB  - In higher animals, complex and robust behaviors are produced by the microscopic
      details of large structured ensembles of neurons. I describe how the emergent
      computational dynamics of a biologically based neural network generates a robust
      natural solution to the problem of categorizing time-varying stimulus patterns
      such as spoken words or animal stereotypical behaviors. The recognition of these
      patterns is made difficult by their substantial variation in cadence and
      duration. The neural circuit behaviors used are similar to those associated with
      brain neural integrators. In the larger context described here, this kind of
      circuit becomes a building block of an entirely different computational algorithm
      for solving complex problems. While the network behavior is simulated in detail,
      a collective view is essential to understanding the results. A closed equation of
      motion for the collective variable describes an algorithm that quantitatively
      accounts for many aspects of the emergent network computation. The feedback
      connections and ongoing activity in the network shape the collective dynamics
      onto a reduced dimensionality manifold of activity space, which defines the
      algorithm and computation actually performed. The external inputs are weak and
      are not the dominant drivers of network activity. 

PMID- 26313597
TI  - Cellular metabolites modulate in vivo signaling of Arabidopsis cryptochrome-1.
AB  - Cryptochromes are blue-light absorbing flavoproteins with multiple signaling
      roles. In plants, cryptochrome (cry1, cry2) biological activity has been linked
      to flavin photoreduction via an electron transport chain to the protein surface
      comprising 3 evolutionarily conserved tryptophan residues known as the 'Trp
      triad.' Mutation of any of the Trp triad residues abolishes photoreduction in
      isolated cryptochrome protein in vitro and therefore had been suggested as
      essential for electron transfer to the flavin. However, photoreduction of the
      flavin in Arabidopsis cry2 proteins occurs in vivo even with mutations in the Trp
      triad, indicating the existence of alternative electron transfer pathways to the
      flavin. These pathways are potentiated by metabolites in the intracellular
      environment including ATP, ADP, AMP, and NADH. In the present work we extend
      these observations to Arabidopsis cryptochrome 1 and demonstrate that Trp triad
      substitution mutants at W400F and W324F positions which are not photoreduced in
      vitro can be photoreduced in whole cell extracts, albeit with reduced efficiency.
      We further show that the flavin signaling state (FADH degrees ) is stabilized in
      an in vivo context. These data illustrate that in vivo modulation by metabolites
      in the cellular environment may play an important role in cryptochrome signaling,
      and are discussed with respect to possible effects on the conformation of the C
      terminal domain to generate the biologically active conformational state.

PMID- 26313599
TI  - Linear Methods for Efficient and Fast Separation of Two Sources Recorded with a
      Single Microphone.
AB  - This letter addresses the problem of separating two speakers from a single
      microphone recording. Three linear methods are tested for source separation, all
      of which operate directly on sound spectrograms: (1) eigenmode analysis of
      covariance difference to identify spectro-temporal features associated with large
      variance for one source and small variance for the other source; (2) maximum
      likelihood demixing in which the mixture is modeled as the sum of two gaussian
      signals and maximum likelihood is used to identify the most likely sources; and
      (3) suppression-regression, in which autoregressive models are trained to
      reproduce one source and suppress the other. These linear approaches are tested
      on the problem of separating a known male from a known female speaker. The
      performance of these algorithms is assessed in terms of the residual error of
      estimated source spectrograms, waveform signal-to-noise ratio, and perceptual
      evaluation of speech quality scores. This work shows that the algorithms compare
      favorably to nonlinear approaches such as nonnegative sparse coding in terms of
      simplicity, performance, and suitability for real-time implementations, and they
      provide benchmark solutions for monaural source separation tasks. 

PMID- 26313600
TI  - Visual Categorization with Random Projection.
AB  - Humans learn categories of complex objects quickly and from a few examples.
      Random projection has been suggested as a means to learn and categorize
      efficiently. We investigate how random projection affects categorization by
      humans and by very simple neural networks on the same stimuli and categorization
      tasks, and how this relates to the robustness of categories. We find that (1)
      drastic reduction in stimulus complexity via random projection does not degrade
      performance in categorization tasks by either humans or simple neural networks,
      (2) human accuracy and neural network accuracy are remarkably correlated, even at
      the level of individual stimuli, and (3) the performance of both is strongly
      indicated by a natural notion of category robustness. 

PMID- 26313601
TI  - Indefinite Proximity Learning: A Review.
AB  - Efficient learning of a data analysis task strongly depends on the data
      representation. Most methods rely on (symmetric) similarity or dissimilarity
      representations by means of metric inner products or distances, providing easy
      access to powerful mathematical formalisms like kernel or branch-and-bound
      approaches. Similarities and dissimilarities are, however, often naturally
      obtained by nonmetric proximity measures that cannot easily be handled by
      classical learning algorithms. Major efforts have been undertaken to provide
      approaches that can either directly be used for such data or to make standard
      methods available for these types of data. We provide a comprehensive survey for
      the field of learning with nonmetric proximities. First, we introduce the
      formalism used in nonmetric spaces and motivate specific treatments for nonmetric
      proximity data. Second, we provide a systematization of the various approaches.
      For each category of approaches, we provide a comparative discussion of the
      individual algorithms and address complexity issues and generalization
      properties. In a summarizing section, we provide a larger experimental study for
      the majority of the algorithms on standard data sets. We also address the problem
      of large-scale proximity learning, which is often overlooked in this context and
      of major importance to make the method relevant in practice. The algorithms we
      discuss are in general applicable for proximity-based clustering, one-class
      classification, classification, regression, and embedding approaches. In the
      experimental part, we focus on classification tasks. 

PMID- 26313602
TI  - Recurrent Neural Network Approach Based on the Integral Representation of the
      Drazin Inverse.
AB  - In this letter, we present the dynamical equation and corresponding artificial
      recurrent neural network for computing the Drazin inverse for arbitrary square
      real matrix, without any restriction on its eigenvalues. Conditions that ensure
      the stability of the defined recurrent neural network as well as its convergence
      toward the Drazin inverse are considered. Several illustrative examples present
      the results of computer simulations. 

PMID- 26313603
TI  - Multiview Bayesian Correlated Component Analysis.
AB  - Correlated component analysis as proposed by Dmochowski, Sajda, Dias, and Parra
      (2012) is a tool for investigating brain process similarity in the responses to
      multiple views of a given stimulus. Correlated components are identified under
      the assumption that the involved spatial networks are identical. Here we propose
      a hierarchical probabilistic model that can infer the level of universality in
      such multiview data, from completely unrelated representations, corresponding to
      canonical correlation analysis, to identical representations as in correlated
      component analysis. This new model, which we denote Bayesian correlated component
      analysis, evaluates favorably against three relevant algorithms in simulated
      data. A well-established benchmark EEG data set is used to further validate the
      new model and infer the variability of spatial representations across multiple
      subjects.

PMID- 26313604
TI  - A Note on Entropy Estimation.
AB  - We compare an entropy estimator H(z) recently discussed by Zhang (2012) with two
      estimators, H(1) and H(2), introduced by Grassberger (2003) and Schurmann (2004).
      We prove the identity H(z) = H(1), which has not been taken into account by Zhang
      (2012). Then we prove that the systematic error (bias) of H(1) is less than or
      equal to the bias of the ordinary likelihood (or plug-in) estimator of entropy.
      Finally, by numerical simulation, we verify that for the most interesting regime
      of small sample estimation and large event spaces, the estimator H(2) has a
      significantly smaller statistical error than H(z).

PMID- 26313605
TI  - Accuracy and Efficiency in Fixed-Point Neural ODE Solvers.
AB  - Simulation of neural behavior on digital architectures often requires the
      solution of ordinary differential equations (ODEs) at each step of the
      simulation. For some neural models, this is a significant computational burden,
      so efficiency is important. Accuracy is also relevant because solutions can be
      sensitive to model parameterization and time step. These issues are emphasized on
      fixed-point processors like the ARM unit used in the SpiNNaker architecture.
      Using the Izhikevich neural model as an example, we explore some solution
      methods, showing how specific techniques can be used to find balanced solutions.
      We have investigated a number of important and related issues, such as
      introducing explicit solver reduction (ESR) for merging an explicit ODE solver
      and autonomous ODE into one algebraic formula, with benefits for both accuracy
      and speed; a simple, efficient mechanism for cancelling the cumulative lag in
      state variables caused by threshold crossing between time steps; an exact result
      for the membrane potential of the Izhikevich model with the other state variable
      held fixed. Parametric variations of the Izhikevich neuron show both similarities
      and differences in terms of algorithms and arithmetic types that perform well,
      making an overall best solution challenging to identify, but we show that
      particular cases can be improved significantly using the techniques described.
      Using a 1 ms simulation time step and 32-bit fixed-point arithmetic to promote
      real-time performance, one of the second-order Runge-Kutta methods looks to be
      the best compromise; Midpoint for speed or Trapezoid for accuracy. SpiNNaker
      offers an unusual combination of low energy use and real-time performance, so
      some compromises on accuracy might be expected. However, with a careful choice of
      approach, results comparable to those of general-purpose systems should be
      possible in many realistic cases. 

PMID- 26313606
TI  - A Simple Label Switching Algorithm for Semisupervised Structural SVMs.
AB  - In structured output learning, obtaining labeled data for real-world applications
      is usually costly, while unlabeled examples are available in abundance.
      Semisupervised structured classification deals with a small number of labeled
      examples and a large number of unlabeled structured data. In this work, we
      consider semisupervised structural support vector machines with domain
      constraints. The optimization problem, which in general is not convex, contains
      the loss terms associated with the labeled and unlabeled examples, along with the
      domain constraints. We propose a simple optimization approach that alternates
      between solving a supervised learning problem and a constraint matching problem.
      Solving the constraint matching problem is difficult for structured prediction,
      and we propose an efficient and effective label switching method to solve it. The
      alternating optimization is carried out within a deterministic annealing
      framework, which helps in effective constraint matching and avoiding poor local
      minima, which are not very useful. The algorithm is simple and easy to implement.
      Further, it is suitable for any structured output learning problem where exact
      inference is available. Experiments on benchmark sequence labeling data sets and
      a natural language parsing data set show that the proposed approach, though
      simple, achieves comparable generalization performance. 

PMID- 26313607
TI  - How should we choose the 'best' embryo? A commentary on behalf of the British
      Fertility Society and the Association of Clinical Embryologists.
AB  - Embryo selection to improve pregnancy rates remains a significant challenge in
      IVF. Non-invasive and invasive methods of embryo selection include morphological
      assessment, metabolomics, time-lapse imaging and preimplantation genetic
      screening. To date, none has been shown conclusively to yield improved
      implantation and live birth rates. This review summarises current understanding
      of methods for embryo selection. 

PMID- 26313608
TI  - The hidden and informal curriculum across the continuum of training: A cross
      sectional qualitative study.
AB  - PURPOSE: The hidden and informal curricula refer to learning in response to
      unarticulated processes and constraints, falling outside the formal medical
      curriculum. The hidden curriculum has been identified as requiring attention
      across all levels of learning. We sought to assess the knowledge and perceptions
      of the hidden and informal curricula across the continuum of learning at a single
      institution. METHODS: Focus groups were held with undergraduate and postgraduate
      learners and faculty to explore knowledge and perceptions relating to the hidden
      and informal curricula. Thematic analysis was conducted both inductively by
      research team members and deductively using questions structured by the existing
      literature. RESULTS: Participants highlighted several themes related to the
      presence of the hidden and informal curricula in medical training and practice,
      including: the privileging of some specialties over others; the reinforcement of
      hierarchies within medicine; and a culture of tolerance towards unprofessional
      behaviors. Participants acknowledged the importance of role modeling in the
      development of professional identities and discussed the deterioration in
      idealism that occurs. CONCLUSIONS: Common issues pertaining to the hidden
      curriculum exist across all levels of learners, including faculty. Increased
      awareness of these issues could allow for the further development of methods to
      address learning within the hidden curriculum.

PMID- 26313609
TI  - Management of intrahepatic cholestasis of pregnancy.
AB  - Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease
      during pregnancy, characterized by otherwise unexplained pruritus in late second
      and third trimester of pregnancy and elevated bile acids and/or transaminases.
      ICP is associated with an increased risk of adverse perinatal outcomes for the
      fetus and the later development of hepatobiliary disease for the mother. Bile
      acids should be monitored throughout pregnancy since fetal risk is increased at
      serum bile acids >40 umol/l. Management of ICP consists of treatment with
      ursodeoxycholic acid, which reduces pruritus. Early elective delivery is common
      practice but should be performed on an individualized basis as long as strong
      evidence supporting this practice is lacking. Mothers should be followed-up for
      normalization of liver function tests 6-12 weeks after delivery. Future research
      in large-scale studies is needed to address the impact of ursodeoxycholic acid
      and early elective delivery on fetal outcome. 

PMID- 26313610
TI  - Adsorption and interaction of CO2 on rutile TiO2(110) surfaces: a combined UHV
      FTIRS and theoretical simulation study.
AB  - CO2 adsorption and interaction on rutile TiO2(110) surfaces was studied by UHV
      FTIRS combined with theoretical simulations. With increasing CO2 exposure, CO2
      adsorbs in succession at the oxygen vacancy (Vo) sites, on the five-coordinated
      Ti cation (Ti5c) sites and the bridging oxygen (Obr) sites at low temperature.
      The coupling has occurred between neighboring CO2 adsorbed on Ti5c sites from
      rather low CO2 coverage (~0.5 ML), leading the nu3(OCO) asymmetric stretching
      vibrations to split into two absorption bands in IR spectra. Two kinds of coupled
      geometries of adjacent CO2 on Ti5c sites are determined by theoretical
      simulations. For the higher CO2 coverage (~1.5 ML), the horizontal adsorption
      configuration along the [11[combining macron]0] azimuth of CO2 adsorbed on Obr
      sites is identified for the first time using polarization- and azimuth-resolved
      RAIRS in experiments. The significant deviation of CO2 from the top of Obr sites
      demonstrates the strong coupling between CO2 adsorbed on Obr and Ti5c sites. 

PMID- 26313611
TI  - Identification of amino acid residues of AcMNPV P143 protein involved in rRNA
      degradation and restricted viral replication in BM-N cells from the silkworm
      Bombyx mori.
AB  - We previously demonstrated that rRNA undergoes rapid and extensive degradation in
      Bombyx mori BM-N cells upon infection with AcMNPV, which is triggered by AcMNPV
      P143 (Ac-P143) protein. Here, we showed that six amino acid residues of Ac-P143
      protein, distributing between positions 514 and 599, are involved in rRNA
      degradation in BM-N cells. The six residues are highly conserved among P143
      proteins from AcMNPV, HycuMNPV, SeMNPV and SpltMNPV, which trigger rRNA
      degradation in BM-N cells upon infection, but are only partially conserved in Bm
      P143 protein, which does not induce rRNA degradation in BM-N cells. We also
      demonstrated that substitution of only two selected residues (N565S/L578F) of Bm
      P143 protein with the corresponding Ac-P143 protein residues generates a mutant
      Bm-P143 protein that is capable of triggering rRNA degradation in BM-N cells.
      These results indicate that BmNPV evolved a unique P143 protein to evade the
      antiviral response and allow replication in B. mori cells. 

PMID- 26313612
TI  - Chronic bacterial prostatitis and chronic pelvic pain syndrome.
AB  - INTRODUCTION: Chronic prostatitis can cause pain and urinary symptoms, and can
      occur either with an active infection (chronic bacterial prostatitis [CBP]) or
      with only pain and no evidence of bacterial causation (chronic pelvic pain
      syndrome [CPPS]). Bacterial prostatitis is characterised by recurrent urinary
      tract infections or infection in the prostate with the same bacterial strain,
      which often results from urinary tract instrumentation. However, the cause and
      natural history of CPPS are unknown and not associated with active infection.
      METHODS AND OUTCOMES: We conducted a systematic overview and aimed to answer the
      following clinical questions: What are the effects of treatments for chronic
      bacterial prostatitis? What are the effects of treatments for chronic pelvic pain
      syndrome? We searched: Medline, Embase, The Cochrane Library, and other important
      databases up to February 2014 (Clinical Evidence overviews are updated
      periodically; please check our website for the most up-to-date version of this
      overview). RESULTS: At this update, searching of electronic databases retrieved
      131 studies. After deduplication and removal of conference abstracts, 67 records
      were screened for inclusion in the overview. Appraisal of titles and abstracts
      led to the exclusion of 51 studies and the further review of 16 full
      publications. Of the 16 full articles evaluated, three systematic reviews and one
      RCT were included at this update. We performed a GRADE evaluation for 14 PICO
      combinations. CONCLUSIONS: In this systematic overview, we categorised the
      efficacy for 12 interventions based on information relating to the effectiveness
      and safety of 5 alpha-reductase inhibitors, allopurinol, alpha-blockers, local
      injections of antimicrobial drugs, mepartricin, non-steroidal anti-inflammatory
      drugs (NSAIDs), oral antimicrobial drugs, pentosan polysulfate, quercetin, sitz
      baths, transurethral microwave thermotherapy (TUMT), and transurethral resection
      of the prostate (TURP).

PMID- 26313613
TI  - Profilin-1 mediated cell-cycle arrest: searching for drug targets.

PMID- 26313614
TI  - Orthostatic Blood Pressure Behavior in People with Mild Cognitive Impairment
      Predicts Conversion to Dementia.
AB  - OBJECTIVES: To compare the patterns of blood pressure (BP) behavior during
      orthostasis in individuals with mild cognitive impairment (MCI) with those of
      controls and to investigate whether orthostatic BP behavior differs between
      individuals with MCI who convert to dementia and those who do not. DESIGN:
      Longitudinal study with 3 years of follow-up. SETTING: Memory clinic in Dublin,
      Ireland, between 2007 and 2012. PARTICIPANTS: Community-dwelling individuals with
      MCI (n = 150) and controls (n = 75). MEASUREMENTS: Orthostatic BP was examined
      using the active standing test with a beat-to-beat continuous BP monitoring
      device in addition to neuropsychological testing. Hazard ratios (HRs) from
      parametric survival models were used to determine whether conversion to dementia
      was independently associated with baseline orthostatic BP variables. RESULTS:
      Individuals with MCI were more likely than controls to have a systolic BP (SBP)
      deficit of greater than 30% 30 seconds after standing (P = .01). Thirty percent
      of participants with MCI (n = 43) converted to dementia within the 3-year follow
      up period. Individuals with MCI with a SBP deficit greater than 30% 30 seconds
      after standing were twice as likely to convert to dementia as those without the
      deficit (HR = 2.77, 95% confidence interval = 1.02-7.50). CONCLUSION: Human
      beings have evolved an elaborate neurological control system to maintain cerebral
      perfusion during orthostatic challenge. In people with MCI, this response is
      impaired and renders them twice as likely to convert to dementia.

PMID- 26313615
TI  - Treatment of methyl orange by nitrogen non-thermal plasma in a corona reactor:
      The role of reactive nitrogen species.
AB  - Methyl orange (MO) azo dye served as model organic pollutant to investigate the
      role of reactive nitrogen species (RNS) in non-thermal plasma (NTP) induced water
      treatments. The results of experiments in which MO aqueous solutions were
      directly exposed to N2-NTP are compared with those of control experiments in
      which MO was allowed to react with nitrite, nitrate and hydrogen peroxide, which
      are species formed in water exposed to N2-NTP. Treatment of MO was also performed
      in PAW, Plasma Activated Water, that is water previously exposed to N2-NTP. Both
      direct N2-NTP and N2-PAW treatments induced the rapid decay of MO. No appreciable
      reaction was instead observed when MO was treated with NO3(-) and H2O2 either
      under acidic or neutral pH. In contrast, in acidic solutions MO decayed rapidly
      when treated with NO2(-) and with a combination of NO2(-) and H2O2. Thorough
      product analysis was carried out by HPLC coupled with UV-vis and ESI-MS/MS
      detectors. In all experiments in which MO reaction was observed, the major
      primary product was a derivative nitro-substituted at the ortho position with
      respect to the N,N-dimethylamino group of MO. The reactions of RNS are discussed
      and a mechanism for the observed nitration products is proposed. 

PMID- 26313616
TI  - Performance of membrane bioreactor (MBR) systems for the treatment of shipboard
      slops: Assessment of hydrocarbon biodegradation and biomass activity under
      salinity variation.
AB  - In order to prevent hydrocarbon discharge at sea from ships, the International
      Maritime Organization (IMO) enacted the MARPOL 73/78 convention in which any oil
      and oil residue discharged in wastewater streams must contain less than 5 ppm
      hydrocarbons. Effective treatment of this petroleum-contaminated water is
      essential prior to its release into the environment, in order to prevent
      pollution problem for marine ecosystems as well as for human health. Therefore,
      two bench scale membrane bioreactors (MBRs) were investigated for hydrocarbon
      biodegradation. The two plants were initially fed with synthetic wastewater
      characterised by an increasing salinity, in order to enhance biomass acclimation
      to salinity. Subsequently, they were fed with a mixture of synthetic wastewater
      and real shipboard slops (with an increasing slops percentage up to 50% by
      volume). The results indicated a satisfactory biomass acclimation level in both
      plants with regards to salinity, providing significant removal efficiencies. The
      real slops exerted an inhibitory effect on the biomass, partially due to
      hydrocarbons as well as to other concomitant influences from other compounds
      contained in the real slops difficult to evaluate a priori. Nevertheless, a
      slight adaptation of the biomass to the new conditions was observed, with
      increasing removal efficiencies, despite the significant slops percentage.

PMID- 26313617
TI  - Dechlorination of chlorinated phenols by subnanoscale Pd 0 /Fe 0 intercalated in
      smectite: pathway, reactivity, and selectivity.
AB  - Smectite clay was employed as templated matrix to prepare subnanoscale
      Pd(0)/Fe(0) particles, and their components as well as intercalated architectures
      were well characterized by X-ray energy dispersive spectroscopy (X-EDS) and X-ray
      diffraction (XRD). Furthermore, as-prepared Pd(0)/Fe(0) subnanoscale
      nanoparticles were evaluated for their dechlorination effect using chlorinated
      phenols as model molecules. As a result, pentachlorophenol (PCP) is selectively
      transformed to phenol in a stepwise dechlorination pathway within 6h, and the
      dechlorination rate constants show linearly relationship with contents of Pd as
      its loadings <0.065%. Comparing with PCP, other chlorinated phenols display
      similar degradation pattern but within much shorter time frame. The
      dechlorination rate of chlorinated phenols increases with decreasing in number of
      -Cl attached to aromatic ring, which can be predicted by the total charge of the
      aromatic ring, exhibiting an inversely linear relationship with the
      dechlorination rates. While the selectivity of dechlorination depends on the
      charges associated with the individual aromatic carbon. Chloro-functional groups
      at the ortho-position are easier to be dechlorinated than that at meta- and para-
      positions yielding primarily 3,4,5-TCP as intermediate from PCP, further to
      phenol. The effective dechlorination warrants their potential utilizations in
      development of in-situ remediation technologies for organic pollutants in
      contaminated water. 

PMID- 26313618
TI  - Squamous Cell Carcinoma Xenografts: Use of VEGFR2-targeted Microbubbles for
      Combined Functional and Molecular US to Monitor Antiangiogenic Therapy Effects.
AB  - PURPOSE: To assess the ability of vascular endothelial growth factor receptor
      type 2 (VEGFR2)-targeted and nontargeted ultrasonography (US) to depict
      antiangiogenic therapy effects and to investigate whether first-pass kinetics
      obtained with VEGFR2-targeted microbubbles provide independent data about tumor
      vascularization. MATERIALS AND METHODS: Governmental approval was obtained for
      animal experiments. Vascularization in response to anti-vascular endothelial
      growth factor receptor or vehicle-control treatment (10 per group) in HaCaT-ras A
      5RT3 xenografts was longitudinally assessed in mice by means of first-pass
      kinetics of nontargeted microbubbles (BR1, BR38; Bracco, Geneva, Switzerland) and
      VEGFR2-targeted microbubbles (BR55, Bracco) before and 4, 7, and 14 days after
      therapy. VEGFR2 expression was determined 8 minutes after BR55 injection with
      destruction-replenishment analysis. US data were validated with
      immunohistochemistry. Significant differences were evaluated with the Mann
      Whitney test. RESULTS: First-pass analysis with BR1, BR38, and BR55 showed
      similar tendencies toward decreasing vascularization, with a stronger decrease in
      tumors treated with anti-VEGF antibody. The median signal intensity (in arbitrary
      units [au]) of anti-VEGF antibody-treated versus control tumors at day 14 was as
      follows: BR1, 5.2 au (interquartile range [IQR], 3.2 au) vs 11.3 au (IQR, 10.0
      au), respectively; BR38, 6.2 au (IQR, 3.5) vs 10.0 au (IQR, 7.8); and BR55, 9.5
      au (IQR, 6.0 au) vs 13.8 au (IQR, 9.8) (P = .0230). VEGFR2 assessment with BR55
      demonstrated significant differences between both groups throughout the therapy
      period (median signal intensity of anti-VEGF antibody-treated vs control tumors:
      0.04 au [IQR, 0.1 au] vs 0.14 au [IQR, 0.08 au], respectively, at day 4, P =
      .0058; 0.04 au [IQR, 0.06 au] vs 0.13 au [IQR, 0.09 au] at day 7, P = .0058; and
      0.06 au [IQR, 0.11 au] vs 0.16 au [IQR, 0.15 au] at day 14, P = .0247).
      Immunohistochemistry confirmed the lower microvessel density and VEGFR2-positive
      area fraction in tumors treated with anti-VEGF antibody. CONCLUSION:
      Antiangiogenic therapy effects were detected earlier and more distinctly with
      VEGFR2-targeted US than with functional US. First-pass analyses with BR55, BR38,
      and BR1 revealed similar results, with a decrease in vascularization during
      therapy. Functional data showed that BR55 is not strongly affected by early
      binding of the microbubbles to VEGFR2. Thus, functional and molecular imaging of
      angiogenesis can be performed with BR55 within one examination.

PMID- 26313619
TI  - SPIO-labeled Yttrium Microspheres for MR Imaging Quantification of Transcatheter
      Intrahepatic Delivery in a Rodent Model.
AB  - PURPOSE: To investigate the qualitative and quantitative impacts of labeling
      yttrium microspheres with increasing amounts of superparamagnetic iron oxide
      (SPIO) material for magnetic resonance (MR) imaging in phantom and rodent models.
      MATERIALS AND METHODS: Animal model studies were approved by the institutional
      Animal Care and Use Committee. The r2* relaxivity for each of four microsphere
      SPIO compositions was determined from 32 phantoms constructed with agarose gel
      and in eight concentrations from each of the four compositions. Intrahepatic
      transcatheter infusion procedures were performed in rats by using each of the
      four compositions before MR imaging to visualize distributions within the liver.
      For quantitative studies, doses of 5, 10, 15, or 20 mg 2% SPIO-labeled yttrium
      microspheres were infused into 24 rats (six rats per group). MR imaging R2*
      measurements were used to quantify the dose delivered to each liver. Pearson
      correlation, analysis of variance, and intraclass correlation analyses were
      performed to compare MR imaging measurements in phantoms and animal models.
      RESULTS: Increased r2* relaxivity was observed with incremental increases of SPIO
      microsphere content. R2* measurements of the 2% SPIO-labeled yttrium microsphere
      concentration were well correlated with known phantom concentrations (R(2) =
      1.00, P < .001) over a broader linear range than observed for the other three
      compositions. Microspheres were heterogeneously distributed within each liver;
      increasing microsphere SPIO content produced marked signal voids. R2*-based
      measurements of 2% SPIO-labeled yttrium microsphere delivery were well correlated
      with infused dose (intraclass correlation coefficient, 0.98; P < .001).
      CONCLUSION: MR imaging R2* measurements of yttrium microspheres labeled with 2%
      SPIO can quantitatively depict in vivo intrahepatic biodistribution in a rat
      model.

PMID- 26313620
TI  - One session treatment for pediatric blood-injection-injury phobia: A controlled
      multiple baseline trial.
AB  - The present study evaluated the effectiveness of a modified One Session Treatment
      (OST), which included an e-therapy homework maintenance program over 4 weeks for
      Blood-Injection-Injury (BII) phobia in children and adolescents. Using a single
      case, non-concurrent multiple-baseline design, 24 children and adolescents (8-18
      years; 7 males, 17 females) with a primary diagnosis of BII phobia were randomly
      assigned to a one, two or three week baseline prior to receiving OST. Primary
      outcome measures included diagnostic severity, diagnostic status, and child and
      parent fear ratings. Secondary outcome measures included avoidance during
      behavioural avoidance tasks (BAT), global functioning and self and parent
      reported anxiety, fear and depression. Efficacy was assessed at post-treatment, 1
      month, and 3-month follow-up. BII symptoms and diagnostic severity remained
      relatively stable during the baseline periods and then significantly improved
      following implementation of the intervention. Treatment response was supported by
      changes across multiple measures, including child, parent and independent
      clinician ratings. At post-treatment 8 of the 24 (33.33%) children were BII
      diagnosis free. Treatment gains improved at follow-ups with 14 (58.33%) children
      diagnosis free at 1-month follow-up and 15 (62.5%) diagnosis free at 3-month
      follow-up. Preliminary findings support the effectiveness of a modified OST
      approach for BII phobic youth with treatment outcomes improving over follow-up
      intervals. 

PMID- 26313621
TI  - Effects of cognitive behavioral therapy in patients with depressive disorder and
      comorbid insomnia: A propensity score-matched outcome study.
AB  - OBJECTIVE: We evaluated the effects of cognitive behavioral therapy for insomnia
      (CBT-I) in inpatients with a diagnosis of depression and comorbid insomnia.
      METHOD: This study used a prospective, parallel-group design. The experimental
      group received CBT-I for no more than 90 min once weekly for 6 weeks and the
      control group only have health education manuals for insomnia. The following
      questionnaires were administered at baseline: the Hamilton Rating Scale for
      Depression (HAM-D), Dysfunctional Beliefs and Attitudes about Sleep (DBAS),
      Presleep Arousal Scale (PSAS), Sleep Hygiene Practice (SHP), and Pittsburgh Sleep
      Quality Index. The questionnaires were readministered after the completion of the
      6-wk CBT-I intervention and 1 month following the completion of CBT-I, to
      determine the effects of the CBT-I intervention over time. The analysis of
      Generalized Estimation Equations was identified the difference between the
      experimental group and the control group by controlling for the variables in BZD
      dose and propensity score of gender, age, and the scores for the DBAS-16, PSAS,
      SHPS, and HAM-D. RESULTS: Consequently, the significant difference in the PSQI
      scores was observed at the 1-month follow-up assessment however, no significant
      intergroup difference in the PSQI scores was found at the completion of the CBT-I
      intervention between two groups. CONCLUSIONS: As a conclusion, we found that
      overall sleep quality significantly improved in patients who received CBT-I after
      we controlled for the BZD dose and propensity score, which suggests that CBT-I
      may represent a useful clinical strategy for improving sleep quality in patients
      with depression and comorbid insomnia.

PMID- 26313622
TI  - Gamma irradiated thermoluminescence response of Ge-doped SiO2 fibre.
AB  - Over the past decade and more, considerable interest has been shown in the
      thermoluminescence (TL) properties of silica-based single-mode optical fibres, in
      particular investigating potential ionising radiation dosimetry applications.
      Herein, study has been made of TL glow curve, dose response, reproducibility and
      fading of 6mol% Ge-doped silica, fabricated in-house and produced in the form of
      cylindrical fibres. Three different pairings of doped-core and silica cladding
      diameters were produced: (40, 241)um, (80, 483)um and (100, 604)um. The TL
      results were compared against that of TLD-100, one of the most sensitive
      commercially available LiF-based TL media. For all three pairings of diameters,
      closely similar TL glow curve were obtained, formed of a single peaked structure
      with a maximum TL yield located between the temperatures 250 and 310 degrees C.
      The TL yield of the fibres were linear over the range of doses investigated, from
      1Gy up to 10Gy, their dose response exceeding that of TLD-100, the samples also
      being found to be reusable, without evidence of degradation. 

PMID- 26313623
TI  - Uranium series disequilibrium studies in Chenchu colony area, Guntur district,
      Andhra Pradesh, India.
AB  - An attempt is made to understand uranium series disequilibrium in unconformity
      proximal related uranium mineralisation in Chenchu colony area, Guntur district,
      Andhra Pradesh, India. The uranium mineralization in Chenchu colony is the
      western continuity of the Koppunuru uranium deposit and predominantly hosted by
      gritty quartzite/conglomerate, which occasionally transgresses to underlying
      basement granite/basic rock. Disequilibrium studies are based on borehole core
      samples (35 boreholes, No. of samples=634) broadly divided in two groups of cover
      rocks of Banganapalle formation (above unconformity) and basement granites (below
      unconformity). Linear regression coefficient between uranium and radium is 0.95,
      which reflects excellent correlation and significant enrichment of parent
      uranium. Disequilibrium studies have indicated predominant disequilibrium in
      favour of parent uranium (35%), which is probably due to the weathering process
      causing migration of some of the radionuclides while dissolution of minerals due
      to groundwater action might have also played a significant role. Further, escape
      of radon might have accentuated the disequilibrium factor resulting in an
      increase in the grade of the mineralization. This is well corroborated by the
      presence of fractures and faults in the study area providing channels for radon
      migration/escape. 

PMID- 26313624
TI  - Improved Formulas for the Calculation of the Electrostatic Contribution to the
      Intermolecular Interaction Energy from Multipolar Expansion of the Electronic
      Distribution.
AB  - We have, within the framework of the molecular mechanics method SIBFA, improved
      the formulation of the Coulomb (electrostatic) energy contribution to the
      intermolecular interaction energy. This was done by integrating "overlap-like"
      terms into two components of the multipolar development used to calculate this
      contribution in SIBFA. The calibration of the new component is done on five water
      dimers by fitting this augmented electrostatic contribution to the corresponding
      Ec term. Several tests are done on (i) representative neutral and ionic hydrogen
      bonded complexes; (ii) the complexes of metal cations (Cu(I) and Cu(II)) with a
      neutral or an anionic ligand; and (iii) a representative stacked complex. The
      improvement brought by the new formulation reduces the difference between the ab
      initio (Ec) and molecular mechanics (EMTP*) values by almost an order of
      magnitude when compared to the values of EMTP calculated using the standard
      method. 

PMID- 26313625
TI  - Reading skills in young adolescents with a history of Specific Language
      Impairment: The role of early semantic capacity.
AB  - This study assessed the reading skills of 19 Spanish-Catalan children with
      Specific Language Impairment (SLI) and 16 age-matched control children. Children
      with SLI have difficulties with oral language comprehension, which may affect
      later reading acquisition. We conducted a longitudinal study examining reading
      acquisition in these children between 8 and 12 years old and we relate this data
      with early oral language acquisition at 6 years old. Compared to the control
      group, the SLI group presented impaired decoding and comprehension skills at age
      8, as evidenced by poor scores in all the assessed tasks. Nevertheless, only text
      comprehension abilities appeared to be impaired at age 12. Individual analyses
      confirmed the presence of comprehension deficits in most of the SLI children.
      Furthermore, early semantic verbal fluency at age 6 appeared to significantly
      predict the reading comprehension capacity of SLI participants at age 12. Our
      results emphasize the importance of semantic capacity at early stages of oral
      language development over the consolidation of reading acquisition at later
      stages. LEARNING OUTCOMES: Readers will recognize the relevance of prior oral
      language impairment, especially semantic capacity, in children with a history of
      SLI as a risk factor for the development of later reading difficulties.

PMID- 26313626
TI  - Framing sound: Using expectations to reduce environmental noise annoyance.
AB  - BACKGROUND: Annoyance reactions to environmental noise, such as wind turbine
      sound, have public health implications given associations between annoyance and
      symptoms related to psychological distress. In the case of wind farms, factors
      contributing to noise annoyance have been theorised to include wind turbine sound
      characteristics, the noise sensitivity of residents, and contextual aspects, such
      as receiving information creating negative expectations about sound exposure.
      OBJECTIVE: The experimental aim was to assess whether receiving positive or
      negative expectations about wind farm sound would differentially influence
      annoyance reactions during exposure to wind farm sound, and also influence
      associations between perceived noise sensitivity and noise annoyance. METHOD:
      Sixty volunteers were randomly assigned to receive either negative or positive
      expectations about wind farm sound. Participants in the negative expectation
      group viewed a presentation which incorporated internet material indicating that
      exposure to wind turbine sound, particularly infrasound, might present a health
      risk. Positive expectation participants viewed a DVD which framed wind farm sound
      positively and included internet information about the health benefits of
      infrasound exposure. Participants were then simultaneously exposed to sub-audible
      infrasound and audible wind farm sound during two 7 min exposure sessions, during
      which they assessed their experience of annoyance. RESULTS: Positive expectation
      participants were significantly less annoyed than negative expectation
      participants, while noise sensitivity only predicted annoyance in the negative
      group. CONCLUSION: Findings suggest accessing negative information about sound is
      likely to trigger annoyance, particularly in noise sensitive people and,
      importantly, portraying sound positively may reduce annoyance reactions, even in
      noise sensitive individuals.

PMID- 26313627
TI  - Strong Resistance to Bending Observed for Nanoparticle Membranes.
AB  - We demonstrate how gold nanoparticle monolayers can be curled up into hollow
      scrolls that make it possible to extract both bending and stretching moduli from
      indentation by atomic force microscopy. We find a bending modulus that is 2
      orders of magnitude larger than predicted by standard continuum elasticity, an
      enhancement we associate with nonlocal microstructural constraints. This finding
      opens up new opportunities for independent control of resistance to bending and
      stretching at the nanoscale. 

PMID- 26313628
TI  - Intermediates Involved in the 2e(-)/2H(+) Reduction of CO2 to CO by Iron(0)
      Porphyrin.
AB  - The reduction of CO2 by an iron porphyrin complex with a hydrogen bonding distal
      pocket involves at least two intermediates. The resonance Raman data of
      intermediate I, which could only be stabilized at -95  degrees C, indicates that
      it is a Fe(II)-CO2(2-) adduct and is followed by an another intermediate II at 
      80  degrees C where the bound CO2 in intermediate I is protonated to form a
      Fe(II)-COOH species. While the initial protonation can be achieved using weak
      proton sources like MeOH and PhOH, the facile heterolytic cleavage of the C-OH
      bond in intermediate II requires strong acids. 

PMID- 26313629
TI  - Continuous propionic acid production with Propionibacterium acidipropionici
      immobilized in a novel xylan hydrogel matrix.
AB  - The cell immobilization potential of a novel xylan based disulfide-crosslinked
      hydrogel matrix reinforced with cellulose nanocrystals was studied with
      continuous cultivation of Propionibacterium acidipropionici using various
      dilution rates. The cells were immobilized to hydrogel beads suspended freely in
      the fermentation broth or else packed into a column connected to a stirred tank
      reactor. The maximum propionic acid productivity for the combined stirred tank
      and column was 0.88gL(-1)h(-1) and the maximum productivity for the column was
      determined to be 1.39gL(-1)h(-1). The maximum propionic acid titer for the
      combined system was 13.9gL(-1) with a dilution rate of 0.06h(-1). Dry cell
      density of 99.7gL(-1) was obtained within the column packed with hydrogel beads
      and productivity of 1.02gL(-1)h(-1) was maintained in the column even with the
      high circulation rate of 3.37h(-1). 

PMID- 26313631
TI  - Comparing self-report and mental chronometry measures of motor imagery ability.
AB  - The present study investigated the relationship between two of the most common
      measures of motor imagery ability, self-report ratings, and chronometric
      assessment. This was done for three types of imagery modalities: external visual
      imagery (EVI), internal visual imagery (IVI), and kinesthetic imagery (KI).
      Measures of imagery ability (i.e. self-report and mental chronometry) were also
      compared across skill levels. Participants (N = 198) completed the Movement
      Imagery Questionnaire-3 (MIQ-3) to generate self-report ratings. Chronometric
      assessment was obtained by recording the duration of each MIQ-3 movement imaged
      and physically performed and then calculating a discrepancy score. There were no
      significant correlations between self-report and mental chronometry for any of
      the three motor imagery types (p > .05). When assessing the different types of
      motor imagery ability using self-report ratings, elite athletes had significantly
      higher KI than IVI, which was in turn significantly higher than EVI (p < .05).
      When assessing motor imagery ability using mental chronometry, there were no
      significant differences in imagery type (p > .05). Findings suggest both measures
      address different components of MI quality and should be used together to obtain
      a more comprehensive assessment of motor imagery ability.

PMID- 26313630
TI  - Rapid production of organic fertilizer by dynamic high-temperature aerobic
      fermentation (DHAF) of food waste.
AB  - Keep composting matrix in continuous collision and friction under a relatively
      high-temperature can significantly accelerate the progress of composting. A
      bioreactor was designed according to the novel process. Using this technology,
      organic fertilizer could be produced within 96h. The electric conductivity (EC)
      and pH value reached to a stable value of 2.35mS/cm and 7.7 after 96h of
      fermentation. The total carbon/total nitrogen (TC/TN) and dissolved
      carbon/dissolved nitrogen (DC/DN) ratio was decrease from 27.3 and 36.2 to 17.4
      and 7.6 respectively. In contrast, it needed 24days to achieve the similar result
      in traditional static composting (TSC). Compost particles with different size
      were analyzed to explore the rapid degradation mechanism of food waste. The
      evidence of anaerobic fermentation was firstly discovered in aerobic composting. 

PMID- 26313632
TI  - Correction: Using a single tablet daily to treat latent tuberculosis infection in
      Brazil: bioequivalence of two different isoniazid formulations (300 mg and 100
      mg) demonstrated by a sensitive and rapid high-performance liquid chromatography
      tandem mass spectrometry method in a randomised, crossover study.
AB  - [This corrects the article DOI: 10.1590/0074-02760140458.]. 

PMID- 26313635
TI  - Facile synthesis of core/shell ZnO/ZnS nanofibers by electrospinning and gas
      phase sulfidation for biosensor applications.
AB  - This study describes a new method of passivating ZnO nanofiber-based devices with
      a ZnS layer. This one-step process was carried out in H2S gas at room
      temperature, and resulted in the formation of core/shell ZnO/ZnS nanofibers. This
      study presents the structural, optical and electrical properties of ZnO/ZnS
      nanofibers formed by a 2 nm ZnS sphalerite crystal shell covering a 5 nm ZnO
      wurtzite crystal core. The passivation process prevented free carriers from
      capture by oxygen molecules and significantly reduced the impact of O2 on
      nanostructure conductivity. The conductivity of the nanofibers was increased by
      three orders of magnitude after the sulfidation, the photoresponse time was
      reduced from 1500 s to 30 s, and the cathodoluminescence intensity increased with
      the sulfidation time thanks to the removal of ZnO surface defects by passivation.
      The ZnO/ZnS nanofibers were stable in water for over 30 days, and in phosphate
      buffers of acidic, neutral and alkaline pH for over 3 days. The by-products of
      the passivation process did not affect the conductivity of the devices. The
      potential of ZnO/ZnS nanofibers for protein biosensing is demonstrated using
      biotin and streptavidin as a model system. The presented ZnS shell preparation
      method can facilitate the construction of future sensors and protects the ZnO
      surface from dissolving in a biological environment. 

PMID- 26313637
TI  - Using solution state NMR spectroscopy to probe NMR invisible gelators.
AB  - Supramolecular hydrogels are formed via the self-assembly of gelator molecules
      upon application of a suitable trigger. The exact nature of this self-assembly
      process has been widely investigated as a practical understanding is vital for
      the informed design of these materials. Solution-state NMR spectroscopy is an
      excellent non-invasive tool to follow the self-assembly of supramolecular
      hydrogels. However, in most cases the self-assembled aggregates are silent by
      conventional (1)H NMR spectroscopy due to the low mobility of the constituent
      molecules, limiting NMR spectroscopy to following only the initial assembly
      step(s). Here, we present a new solution-state NMR spectroscopic method which
      allows the entire self-assembly process of a dipeptide gelator to be followed.
      This gelator forms transparent hydrogels by a multi-stage assembly process when
      the pH of an initially alkaline solution is lowered via the hydrolysis of glucono
      delta-lactone (GdL). Changes in the charge, hydrophobicity and relative
      arrangement of the supramolecular aggregates can be followed throughout the
      assembly process by measuring the residual quadrupolar couplings (RQCs) of
      various molecular probes (here, (14)NH4(+) and isopropanol-d8), along with the
      NMR relaxation rates of (23)Na(+). The initially-formed aggregates comprise
      negatively charged fibrils which gradually lose their charge and become
      increasingly hydrophobic as the pH falls, eventually resulting in a macroscopic
      contraction of the hydrogel. We also demonstrate that the in situ measurement of
      pH by NMR spectroscopy is both convenient and accurate, representing a useful
      tool for the characterisation of self-assembly processes by NMR. 

PMID- 26313636
TI  - (1)H MRS: a potential biomarker of in utero placental function.
AB  - The placenta is a temporary organ that is essential for a healthy pregnancy. It
      performs several important functions, including the transport of nutrients, the
      removal of waste products and the metabolism of certain substances. Placental
      disorders have been found to account for over 50% of stillbirths. Despite this,
      there are currently no methods available to directly and non-invasively assess
      placental function in utero. The primary aim of this pilot study was to
      investigate the use of (1)H MRS for this purpose. (1)H MRS offers the possibility
      to detect several placental metabolites, including choline, lipids and the amino
      acids glutamine and glutamate (Glx), which are vital to fetal development and
      placental function. Here, in utero placental spectra were acquired from nine
      small for gestational age (SGA) pregnancies, a cohort who are at increased risk
      of perinatal morbidity and mortality, and from nine healthy gestation-matched
      pregnancies. All subjects were between 26 and 39 weeks of gestation. Placenta
      Glx, choline and lipids at 1.3 and 0.9 ppm were quantified as amplitude ratios to
      that of intrinsic H2O. Wilcoxon signed rank tests indicated a significant
      difference in Glx/H2O (p = 0.024) between the two groups, but not in choline/H2O
      (p = 0.722) or in either lipid/H2O ratio (1.3 ppm, p = 0.813; 0.9 ppm, p =
      0.058). This study has demonstrated that (1)H MRS has potential for the detection
      of placental metabolites in utero. This warrants further investigation as a tool
      for the monitoring of placental function.

PMID- 26313638
TI  - Segregation of materials in double precursor electron-beam-induced-deposition: a
      route to functional magnetic nanostructures.
AB  - Here we report an observation of the phenomenon of spatial segregation of two
      materials in double precursor electron beam induced deposition. Segregation
      occurs under proper deposition conditions in a single spot illumination due to
      generic variation of electron current density within an electron beam. Combining
      precursors for magnetic (dicobaltoctacarbonyl) and non-magnetic (tetraethyl
      orthosilicate) properties we demonstrate a one-step fabrication process for
      magnetic tubules at the scale of 100 nm. Electron holography applied on the cross
      section of thus prepared tubules reveals the concentration of the magnetic field
      in the cobalt rich shell, corroborating spatially distributed functionality. We
      elaborate the numerical model describing the observed phenomenon and defining the
      conditions for its practical achievement. 

PMID- 26313639
TI  - In vitro M-like cells genesis through a tissue-engineered triple-culture
      intestinal model.
AB  - Although fewer in number, M-cells are considered antigen sampling cells, acting
      as a gateway for antigens from the gut lumen and presenting an impressive
      aptitude for particle transcytosis. These features make M-cells attractive
      targets for oral drug delivery studies, but this has been poorly explored. New
      and reproducible tissue-like in vitro models for studying intestinal sampling and
      permeability mechanisms are needed. The combination of different cell players in
      such models offers improved microenvironments with higher physiologic relevance.
      Here, a tissue-engineered model was established, by co-culturing Caco-2
      absorptive cells, HT29-MTX mucus-producing cells and Raji B lymphocytes. After 3
      weeks of cell co-culture, the presence of M-like cells was evidenced by the loss
      of brush-border organization, detected by the lack of microvilli. The triple
      culture model showed to be efficient for insulin transport, a process that was
      influenced by the tightness of junctions between epithelial cells and the
      presence of mucus and M-like cells. Ultimately, the proposed tissue-engineered
      model provides a more complete and reliable tool to perform drug permeability
      tests, as compared to traditional models, and may also find applicability as an
      in vitro system to study transdifferentiation mechanisms of M cells.

PMID- 26313640
TI  - Application of a two-pool model to soil carbon dynamics under elevated CO2.
AB  - Elevated atmospheric CO2 concentrations increase plant productivity and affect
      soil microbial communities, with possible consequences for the turnover rate of
      soil carbon (C) pools and feedbacks to the atmosphere. In a previous analysis
      (Van Groenigen et al., 2014), we used experimental data to inform a one-pool
      model and showed that elevated CO2 increases the decomposition rate of soil
      organic C, negating the storage potential of soil. However, a two-pool soil model
      can potentially explain patterns of soil C dynamics without invoking effects of
      CO2 on decomposition rates. To address this issue, we refit our data to a two
      pool soil C model. We found that CO2 enrichment increases decomposition rates of
      both fast and slow C pools. In addition, elevated CO2 decreased the carbon use
      efficiency of soil microbes (CUE), thereby further reducing soil C storage. These
      findings are consistent with numerous empirical studies and corroborate the
      results from our previous analysis. To facilitate understanding of C dynamics, we
      suggest that empirical and theoretical studies incorporate multiple soil C pools
      with potentially variable decomposition rates. 

PMID- 26313641
TI  - Calix[4]pyrroles with Shortest Possible Strap: Exclusively Selective toward
      Fluoride Ion.
AB  - Four new calix[4]pyrroles with the shortest possible strap so far through ortho
      linking of the aromatic unit have been synthesized, including a naphthalene
      derived fluorescent receptor. They show exclusive selectivity toward the fluoride
      ion as confirmed by (1)H NMR, isothermal titration calorimetry, and fluorescence
      spectroscopic study. Anion affinity could also be modulated further via
      functionalization at the strap. Computational analysis displays calix[4]pyrroles
      binding to fluoride ion in a very unusual 1,3-alternate conformation where the
      anion resides on the opposite side of the strap. 

PMID- 26313642
TI  - Monitoring HIV Prevention Programme Outcomes among Key Populations in Kenya:
      Findings from a National Survey.
AB  - In preparation for the implementation of the Kenya AIDS Strategic Framework
      2014/15-2018/19, the Kenya National AIDS and STI Control Programme facilitated a
      national polling booth survey as part of a baseline assessment of HIV-related
      risk behaviours among FSWs, MSM, and PWID, and their utilization of existing
      preventive interventions, as well as structural factors that may influence KPs'
      vulnerability to HIV. The survey was conducted among "key populations" (female
      sex workers, men who have sex with men, and people who inject drugs) to
      understand current HIV risk and prevention behaviours, utilization of existing
      programmes and services, and experiences of violence. In total, 3,448 female sex
      workers, 1,308 men who have sex with men, and 690 people who inject drugs were
      randomly selected to participate in polling booth survey sessions from seven
      priority sites. Survey responses were aggregated and descriptive statistics
      derived. In general, reported condom use among all key populations was quite high
      with paying clients, and lower with regular, non-paying partners. Many
      participants reported unavailability of condoms or clean injecting equipment
      within the past month. Exposure to, and utilization of, existing HIV prevention
      services varied significantly among the groups, and was reported least commonly
      by female sex workers. Encouragingly, approximately three-quarters of all key
      population members reported receiving an HIV test in the past three months. All
      key population groups reported experiencing high levels of physical and sexual
      violence from partners/clients, and/or arrest and violence by law enforcement
      officials. Although some of the findings are encouraging, there is room for
      improvement in HIV prevention programmes and services for key populations across
      Kenya. 

PMID- 26313643
TI  - pH-Driven Polymorphism of Insulin Amyloid-Like Fibrils.
AB  - Prions are infective proteins, which can self-assemble into different strain
      conformations, leading to different disease phenotypes. An increasing number of
      studies suggest that prion-like self-propagation may be a common feature of
      amyloid-like structures. Thus it is important to unravel every possible factor
      leading to the formation of different amyloid strains. Here we report on the
      formation of two types of insulin amyloid-like fibrils with distinct infrared
      spectroscopic features grown under slightly different pH conditions. Similar to
      prion strains, both insulin fibril types are able to self-propagate their
      conformational template under conditions, favoring spontaneous formation of
      different type fibrils. The low-pH-induced insulin amyloid strain is structurally
      very similar to previously reported strains formed either in the presence of 20%
      ethanol, or by modification of the amino acid sequence of insulin. A deeper
      analysis of literature data in the context of our current findings suggests a
      shift of the monomer-dimer equilibrium of insulin as a possible factor
      controlling the formation of different strains. 

PMID- 26313646
TI  - Fracture risk and mortality post-kidney transplantation.
AB  - BACKGROUND: Fractures are associated with high morbidity and economic costs.
      There is a paucity of information on fractures after kidney transplantation
      outside the United States. METHODS: Data were obtained from the Hospital Episode
      Statistics database on kidney transplants performed in England between 2001 and
      2013 and post-transplant fracture-related hospitalization. Mortality data were
      obtained from the Office for National Statistics. RESULTS: In total, 21 769 first
      kidney transplant procedures were analyzed with 112 512 patient-years follow-up.
      Overall, 836 (3.8%) kidney allograft recipients developed a fracture requiring
      hospitalization. Event rate was 9.99 for any fracture and 1.54 for a hip fracture
      per 1000 patient-years. Accounting for the competing risk of mortality,
      increasing age, female gender, white ethnicity, and a history of pre-transplant
      diabetes mellitus or previous fracture were associated with increased fracture
      risk post-kidney transplantation. Death occurred in 2407 (11.1%) kidney allograft
      recipients, with 173 deaths occurring post-fracture. In an extended Cox model,
      hip fracture as a time-varying factor was independently associated with an
      increased risk of death (hazard ratio, 3.288; 95% confidence intervals, 2.513
      4.301; p < 0.001). CONCLUSIONS: Fracture rates in English kidney transplant
      recipients are lower than previously reported in US cohorts. Sustaining a hip
      fracture is associated with an increased mortality risk. Our results can be used
      to power future fracture prevention trials.

PMID- 26313645
TI  - The Rsb Phosphoregulatory Network Controls Availability of the Primary Sigma
      Factor in Chlamydia trachomatis and Influences the Kinetics of Growth and
      Development.
AB  - Chlamydia trachomatis is an obligate intracellular human pathogen that exhibits
      stage-specific gene transcription throughout a biphasic developmental cycle. The
      mechanisms that control modulation in transcription and associated phenotypic
      changes are poorly understood. This study provides evidence that a switch-protein
      kinase regulatory network controls availability of sigma66, the main sigma
      subunit for transcription in Chlamydia. In vitro analysis revealed that a
      putative switch-protein kinase regulator, RsbW, is capable of interacting
      directly with sigma66, as well as phosphorylating its own antagonist, RsbV1,
      rendering it inactive. Conversely, the putative PP2C-like phosphatase domain of
      chlamydial RsbU was capable of reverting RsbV1 into its active state. Recent
      advances in genetic manipulation of Chlamydia were employed to inactivate rsbV1,
      as well as to increase the expression levels of rsbW or rsbV1, in vivo.
      Representative sigma66-dependent gene transcription was repressed in the absence
      of rsbV1 or upon increased expression of RsbW, and increased upon elevated
      expression of RsbV1. These effects on housekeeping transcription were also
      correlated to several measures of growth and development. A model is proposed
      where the relative levels of active antagonist (RsbV1) and switch-protein anti
      sigma factor (RsbW) control the availability of sigma66 and subsequently act as a
      molecular 'throttle' for Chlamydia growth and development.

PMID- 26313648
TI  - Interannual Changes in Biomass Affect the Spatial Aggregations of Anchovy and
      Sardine as Evidenced by Geostatistical and Spatial Indicators.
AB  - Geostatistical techniques were applied and a series of spatial indicators were
      calculated (occupation, aggregation, location, dispersion, spatial
      autocorrelation and overlap) to characterize the spatial distributions of
      European anchovy and sardine during summer. Two ecosystems were compared for this
      purpose, both located in the Mediterranean Sea: the Strait of Sicily (upwelling
      area) and the North Aegean Sea (continental shelf area, influenced by
      freshwater). Although the biomass of anchovy and sardine presented high
      interannual variability in both areas, the location of the centres of gravity and
      the main spatial patches of their populations were very similar between years.
      The size of the patches representing the dominant part of the abundance (80%) was
      mostly ecosystem- and species-specific. Occupation (area of presence) appears to
      be shaped by the extent of suitable habitats in each ecosystem whereas
      aggregation patterns (how the populations are distributed within the area of
      presence) were species-specific and related to levels of population biomass. In
      the upwelling area, both species showed consistently higher occupation values
      compared to the continental shelf area. Certain characteristics of the spatial
      distribution of sardine (e.g. spreading area, overlapping with anchovy) differed
      substantially between the two ecosystems. Principal component analysis of
      geostatistical and spatial indicators revealed that biomass was significantly
      related to a suite of, rather than single, spatial indicators. At the spatial
      scale of our study, strong correlations emerged between biomass and the first
      principal component axis with highly positive loadings for occupation,
      aggregation and patchiness, independently of species and ecosystem. Overlapping
      between anchovy and sardine increased with the increase of sardine biomass but
      decreased with the increase of anchovy. This contrasting pattern was attributed
      to the location of the respective major patches combined with the specific
      occupation patterns of the two species. The potential use of spatial indices as
      auxiliary stock monitoring indicators is discussed.

PMID- 26313647
TI  - Involvement of Antizyme Characterized from the Small Abalone Haliotis
      diversicolor in Gonadal Development.
AB  - The small abalone Haliotis diversicolor is an economically important mollusk that
      is widely cultivated in Southern China. Gonad precocity may affect the
      aquaculture of small abalone. Polyamines, which are small cationic molecules
      essential for cellular proliferation, may affect gonadal development. Ornithine
      decarboxylase (ODC) and antizyme (AZ) are essential elements of a feedback
      circuit that regulates cellular polyamines. This paper presents the molecular
      cloning and characterization of AZ from small abalone. Sequence analysis showed
      that the cDNA sequence of H. diversicolor AZ (HdiODCAZ) consisted of two
      overlapping open reading frames (ORFs) and conformed to the +1 frameshift
      property of the frame. Thin Layer chromatography (TLC) analysis suggested that
      the expressed protein encoded by +1 ORF2 was the functional AZ that targets ODC
      to 26S proteasome degradation. The result demonstrated that the expression level
      of AZ was higher than that of ODC in the ovary of small abalone. In addition, the
      expression profiles of ODC and AZ at the different development stages of the
      ovary indicated that these two genes might be involved in the gonadal development
      of small abalone. 

PMID- 26313650
TI  - Separate and combined effects of gabapentin and [INCREMENT]9-tetrahydrocannabinol
      in humans discriminating [INCREMENT]9-tetrahydrocannabinol.
AB  - The aim of the present study was to examine a potential mechanism of action of
      gabapentin to manage cannabis-use disorders by determining the interoceptive
      effects of gabapentin in cannabis users discriminating [INCREMENT]
      tetrahydrocannabinol ([INCREMENT]-THC) using a pharmacologically selective drug
      discrimination procedure. Eight cannabis users learned to discriminate 30 mg oral
      [INCREMENT]-THC from placebo and then received gabapentin (600 and 1200 mg),
      [INCREMENT]-THC (5, 15, and 30 mg), and placebo alone and in combination. Self
      report, task performance, and physiological measures were also collected.
      [INCREMENT]-THC served as a discriminative stimulus, produced positive subjective
      effects, elevated heart rate, and impaired psychomotor performance. Both doses of
      gabapentin substituted for the [INCREMENT]-THC discriminative stimulus and
      engendered subjective and performance-impairing effects that overlapped with
      those of [INCREMENT]-THC when administered alone. When administered concurrently,
      gabapentin shifted the discriminative-stimulus effects of [INCREMENT]-THC
      leftward/upward, and combinations of [INCREMENT]-THC and gabapentin generally
      produced larger effects on cannabinoid-sensitive outcomes relative to [INCREMENT]
      THC alone. These results suggest that one mechanism by which gabapentin might
      facilitate cannabis abstinence is by producing effects that overlap with those of
      cannabinoids. 

PMID- 26313651
TI  - Near Infrared Photoimmunotherapy Targeting EGFR Positive Triple Negative Breast
      Cancer: Optimizing the Conjugate-Light Regimen.
AB  - AIM: Triple-negative breast cancer (TNBC) is considered one of the most
      aggressive subtypes of breast cancer. Near infrared photoimmunotherapy (NIR-PIT)
      is a cancer treatment that employs an antibody-photosensitizer conjugate (APC)
      followed by exposure of NIR light for activating selective cytotoxicity on
      targeted cancer cells and may have application to TNBC. In order to minimize the
      dose of APC while maximizing the therapeutic effects, dosing of the APC and NIR
      light need to be optimized. In this study, we investigate in vitro and in vivo
      efficacy of cetuximab (cet)-IR700 NIR-PIT on two breast cancer models MDAMB231
      (TNBC, EGFR moderate) and MDAMB468 (TNBC, EGFR high) cell lines, and demonstrate
      a method to optimize the dosing APC and NIR light. METHOD: After validating in
      vitro cell-specific cytotoxicity, NIR-PIT therapeutic effects were investigated
      in mouse models using cell lines derived from TNBC tumors. Tumor-bearing mice
      were separated into 4 groups for the following treatments: (1) no treatment
      (control); (2) 300 MUg of cet-IR700 i.v., (APC i.v. only); (3) NIR light exposure
      only, NIR light was administered at 50 J/cm2 on day 1 and 100 J/cm2 on day 2 (NIR
      light only); (4) 300 MUg of cet-IR700 i.v., NIR light was administered at 50
      J/cm2 on day 1 after injection and 100 J/cm2 of light on day 2 after injection
      (one shot NIR-PIT). To compare different treatment regimens with a fixed dose of
      APC, we added the following treatments (5) 100 MUg of cet-IR700 i.v., NIR light
      administered at 50 J/cm2 on day 1 and 50 MUg of cet-IR700 i.v. immediately after
      NIR-PIT, then NIR light was administered at 100 J/cm2 on day 2, which were
      performed two times every week ("two split" NIR-PIT) and (6) 100 MUg of cet-IR700
      i.v., NIR light was administered at 50 J/cm2 on day 1 and 100 J/cm2 on day 2,
      which were performed three times per week ("three split" NIR-PIT). RESULT: Both
      specific binding and NIR-PIT effects were greater with MDAMB468 than MDAMB231
      cells in vitro. Tumor accumulation of cet-IR700 in MDAMB468 tumors was
      significantly higher (p < 0.05) than in MDAMB231 tumors in vivo. Tumor growth and
      survival of MDAMB231 tumor bearing mice was significantly lower in the NIR-PIT
      treatment group (p < 0.05). In MDAMB468 bearing mice, tumor growth and survival
      was significantly improved in the NIR-PIT treatment groups in all treatment
      regimens (one shot NIR-PIT; p < 0.05, "two split" NIR-PIT; p < 0.01, "three
      split" NIR-PIT; p < 0.001) compared with control groups. CONCLUSION: NIR-PIT for
      TNBC was effective regardless of expression of EGFR, however, greater cell
      killing was shown with higher EGFR expression tumor in vitro. In all treatment
      regimens, NIR-PIT suppressed tumor growth, resulting in significantly prolonged
      survival that further improved by splitting the APC dose and using repeated light
      exposures.

PMID- 26313652
TI  - Value of the 340B Drug Discount Program.

PMID- 26313653
TI  - Patient blood management to reduce surgical risk.
AB  - BACKGROUND: Preoperative anaemia and perioperative blood transfusion are both
      identifiable and preventable surgical risks. Patient blood management is a
      multimodal approach to address this issue. It focuses on three pillars of care:
      the detection and treatment of preoperative anaemia; the reduction of
      perioperative blood loss; and harnessing and optimizing the patient-specific
      physiological reserve of anaemia, including restrictive haemoglobin transfusion
      triggers. This article reviews why patient blood management is needed and
      strategies for its incorporation into surgical pathways. METHODS: Studies
      investigating the three pillars of patient blood management were identified using
      PubMed, focusing on recent evidence-based guidance for perioperative management.
      RESULTS: Anaemia is common in surgical practice. Both anaemia and blood
      transfusion are independently associated with adverse outcomes. Functional iron
      deficiency (iron restriction due to increased levels of hepcidin) is the most
      common cause of preoperative anaemia, and should be treated with intravenous
      iron. Intraoperative blood loss can be reduced with antifibrinolytic drugs such
      as tranexamic acid, and cell salvage should be used. A restrictive transfusion
      practice should be the standard of care after surgery. CONCLUSION: The
      significance of preoperative anaemia appears underappreciated, and its detection
      should lead to routine investigation and treatment before elective surgery. The
      risks of unnecessary blood transfusion are increasingly being recognized.
      Strategic adoption of patient blood management in surgical practice is
      recommended, and will reduce costs and improve outcomes in surgery.

PMID- 26313654
TI  - MiR-378b Promotes Differentiation of Keratinocytes through NKX3.1.
AB  - MicroRNA (miRNA) is a kind of short non-coding RNA, involved in various cellular
      processes. During keratinocyte differentiation, miRNAs act as important
      regulators. In this study, we demonstrated by microarray assay that the
      expression of miR-378b significantly increased during keratinocytes
      differentiation. Our findings showed that miR-378b could inhibit proliferation,
      migration and differentiation in keratinocytes. Luciferase reporter assays showed
      that miR-378b directly target NKX3.1. Silencing of NKX3.1 could coincide with the
      effects of miR-24 overexpression. In conclusion, our results demonstrate miR-378b
      promote keratinocytes differentiation by targeting NKX3.1. Manipulation of miR
      378b may afford a new strategy to clinic treatment of skin injury and repair. 

PMID- 26313655
TI  - A novel colorimetric sensor for Hg(2+) based on hybridization chain reaction and
      silver nanowire amplification.
AB  - Through the silver ion catalysis to form colored KMnO4, and combined with the DNA
      hybridization chain reaction and silver nanowire for signal amplification, a
      highly sensitive and selective colorimetric sensor has been developed for the
      detection of Hg(2+). 

PMID- 26313656
TI  - Water Adsorption in Wood Microfibril-Hemicellulose System: Role of the
      Crystalline-Amorphous Interface.
AB  - A two-phase model of a wood microfibril consisting of crystalline cellulose and
      amorphous hemicellulose is investigated with molecular dynamics in full range of
      sorption to understand the molecular origin of swelling and weakening of wood.
      Water is adsorbed in hemicellulose, and an excess of sorption is found at the
      interface, while no sorption occurs within cellulose. Water molecules adsorbed on
      the interface push away polymer chains, forcing the two phases to separate and
      causing breaking of h-bonds, particularly pronounced on the interface. Existence
      of two different regions in moisture response is demonstrated. At low moisture
      content, water is uniformly adsorbed within hemicellulose, breaking a small
      amount of hydrogen bonds. Microfibril does not swell, and the porosity does not
      change. As moisture content increases, water is adsorbed preferentially at the
      interface, which leads to additional swelling and porosity increase at the
      interface. Young's and shear moduli decrease importantly due to breaking of h
      bonds and screening of the long-range interactions. 

PMID- 26313658
TI  - Computation of spine intervertebral motions in scoliotic patients: a multibody
      approach.

PMID- 26313659
TI  - Geochemical control processes and potential sediment toxicity in a mine-impacted
      lake.
AB  - Geochemical parameters and major ion concentrations from sediments of a
      freshwater lake in the town of Atvidaberg, southeastern, Sweden, were used to
      identify the geochemical processes that control the water chemistry. The lake
      sediments are anoxic, characterized by reduced sulfur and sulfidic minerals. The
      hypothesis tested is that in sulfidic-anaerobic contaminated sediments, the
      presence of redox potential changes creates a favorable condition for sulfide
      oxidation, resulting in the release of potentially toxic metals. The acid
      volatile sulfide (AVS) contents ranged from 5.5 MUmol/g to 16 MUmol/g of dry
      sediment. Comparison of total mine tailing metals (?mine tailing metals) with
      simultaneously extracted metals (SEM) in sediments indicates that up to 20% of
      the ?mine tailing metals are bound to the solid phase as AVS. Consequently, the
      AVS and SEM analysis classified all sediment samples as potentially toxic in
      terms of heavy metal concentrations (i.e., SEM to AVS ratio distribution > 1).
      Evaluation of hydrogeochemical data suggests that calcite dissolution, iron (III)
      oxyhydroxysulfate mineral jarosite (H-jarosite) precipitation, hematite
      precipitation, and siderite precipitation are the most prevailing geochemical
      processes that control the geochemical interactions between the water column and
      sediment in a mine-impacted lake. The geochemical processes were verified and
      quantified using a chemical equilibrium modeling program, Visual MINTEQ, Ver 3.1,
      beta. The identified geochemical processes create an environment in which the
      characteristics of sulfate-rich waters and acidic-iron produce the geochemical
      conditions for acid mine drainage and mobilization of toxic metals.

PMID- 26313660
TI  - A Cellular Compatible Chitosan Nanoparticle Surface for Isolation and In Situ
      Culture of Rare Number CTCs.
AB  - Circulating tumor cell (CTC) isolation has attracted a great deal of research
      interest in recent years. However, there are still some challenges, including
      purity as well as viability of the captured CTCs, resulting from nanoscale
      structures and inorganic nanomaterials. Here, a chitosan nanoparticle surface is
      first fabricated by electrospray to provide a cellular compatible interface. The
      "soft" substrate, further modified by polyethylene glycol (PEG) as an antifouling
      molecule and DNA aptamer as a specific capture molecule, has a hydrophilic nature
      and is capable of specific capture of viable rare CTCs from artificial white
      blood cell (WBC) samples. Furthermore, a subsequent in situ culture strategy
      based on the developed cellular compatible soft interface is introduced for
      further purification and proliferation of the captured rare number target cells.
      The WBCs are weeded out after 2 d, and after a 7 d proliferation nearly 200 MCF-7
      cells are obtained from 7 target cells with more than 90% purity. This work
      provides a promising strategy for viable isolation and purification of rare CTCs
      and it has great potential for achieving clinical validity. 

PMID- 26313661
TI  - Baseline and Trend of Lymphocyte-to-Monocyte Ratio as Prognostic Factors in
      Epidermal Growth Factor Receptor Mutant Non-Small Cell Lung Cancer Patients
      Treated with First-Line Epidermal Growth Factor Receptor Tyrosine Kinase
      Inhibitors.
AB  - BACKGROUND: Patients with early-stage lung cancer who have a high baseline
      lymphocyte-to-monocyte ratio (LMR) have a favorable prognosis. However, the
      prognostic significance of LMR in patients with advanced-stage EGFR-mutant non
      small cell lung cancer (NSCLC) receiving first-line epidermal growth factor
      receptor (EGFR)-tyrosine kinase inhibitors (TKIs) has not been established. We
      conducted a retrospective analysis to investigate the influence of LMR on
      clinical outcomes including progression-free survival (PFS) and overall survival
      (OS) in EGFR-mutant patients with NSCLC. MATERIALS AND METHODS: Of 1310 lung
      cancer patients diagnosed between January 2011 and October 2013, 253 patients
      receiving first-line EGFR-TKIs for EGFR-mutant NSCLC were included. The cut-off
      values for baseline and the 1-month-to-baseline ratio of LMR (MBR), determined by
      using receiver operating characteristic curves, were 3.29 and 0.63, respectively.
      Patients were divided into 3 prognostic groups: high LMR and MBR, high LMR or
      MBR, and low LMR and MBR. RESULTS: The mean patient age was 65.2 years, and 41%
      were men. The median PFS and OS were 10.3 and 22.0 months, respectively. The PFS
      in patients with high LMR and MBR, high LMR or MBR, and low LMR and MBR were
      15.4, 7.1, and 2.0 months, respectively (p < 0.001), whereas the OS were 32.6,
      13.7, and 5.1 months, respectively (p < 0.001). CONCLUSION: A combination of
      baseline and trend of LMR can be used to identify patients with a high mortality
      risk in EGFR-mutant NSCLC patients receiving first-line EGFR-TKIs.

PMID- 26313662
TI  - HLA class I is most tightly linked to levels of tapasin compared with other
      antigen-processing proteins in glioblastoma.
AB  - BACKGROUND: Tumour cells can evade the immune system by dysregulation of human
      leukocyte antigens (HLA-I). Low quantity and/or altered quality of HLA-I cell
      surface expression is the result of either HLA-I alterations or dysregulations of
      proteins of the antigen-processing machinery (APM). Tapasin is an APM protein
      dedicated to the maturation of HLA-I and dysregulation of tapasin has been linked
      to higher malignancy in several different tumours. METHODS: We studied the
      expression of APM components and HLA-I, as well as HLA-I tapasin-dependency
      profiles in glioblastoma tissues and corresponding cell lines. RESULTS: Tapasin
      displayed the strongest correlation to HLA-I heavy chain but also clustered with
      beta2-microglobulin, transporter associated with antigen processing (TAP) and
      LMP. Moreover, tapasin also correlated to survival of glioblastoma patients. Some
      APM components, for example, TAP1/TAP2 and LMP2/LMP7, showed variable but
      coordinated expression, whereas ERAP1/ERAP2 displayed an imbalanced expression
      pattern. Furthermore, analysis of HLA-I profiles revealed variable tapasin
      dependence of HLA-I allomorphs in glioblastoma patients. CONCLUSIONS: Expression
      of APM proteins is highly variable between glioblastomas. Tapasin stands out as
      the APM component strongest correlated to HLA-I expression and we proved that HLA
      I profiles in glioblastoma patients include tapasin-dependent allomorphs. The
      level of tapasin was also correlated with patient survival time. Our results
      support the need for individualisation of immunotherapy protocols.

PMID- 26313663
TI  - Brain metastases in gastro-oesophageal adenocarcinoma: insights into the role of
      the human epidermal growth factor receptor 2 (HER2).
AB  - BACKGROUND: Gastro-oesophageal adenocarcinomas rarely metastasize to the central
      nervous system (CNS). The role of the human epidermal growth factor receptor 2
      (HER2) in patients with these cancers and CNS involvement is presently unknown.
      PATIENTS AND METHODS: A multicentre registry was established to collect data from
      patients with gastro-oesophageal adenocarcinomas and CNS involvement both
      retrospectively and prospectively. Inclusion in the study required a predefined
      clinical data set, a central neuro-radiological or histopathological confirmation
      of metastatic CNS involvement and central assessment of HER2 by
      immunohistochemistry (IHC) and in situ hybridisation (ISH). In addition,
      expression of E-cadherin and DNA mismatch repair (MMR) proteins were assessed by
      IHC. RESULTS: One hundred patients fulfilled the inclusion criteria. The
      population's median age was 59 years (interquartile range: 54-68), of which 85
      (85%) were male. Twenty-five patients were of Asian and 75 of Caucasian origin.
      HER2 status was positive in 36% (95% CI: 26.6-46.2) of cases. Median time from
      initial diagnosis to the development of brain metastases (BMets) or
      leptomeningeal carcinomatosis (LC) was 9.9 months (95% CI: 8.5-15.0). Median
      overall survival from diagnosis was 16.9 months (95% CI: 14.0-20.7) and was not
      related to the HER2 status. E-cadherin loss was observed in 9% of cases and loss
      of expression in at least one DNA MMR proteins in 6%. CONCLUSIONS: The proportion
      of a positive HER2 status in patients with gastro-oesophageal adenocarcinoma and
      CNS involvement was higher than expected. The impact of anti-HER2 therapies
      should be studied prospectively.

PMID- 26313666
TI  - The exclusion of people living with HIV (PLWH) from clinical trials in lymphoma.
AB  - BACKGROUND: The prognosis of non-Hodgkin lymphoma and Hodgkin lymphoma is not
      affected by HIV serostatus, yet people living with HIV (PLWH) are frequently
      excluded from clinical trials in lymphoma. METHODS: The UK NIHR Clinical Research
      Network Study Portfolio website was used to identify all the open clinical trials
      in lymphoma in the United Kingdom in January 2015. Trials that excluded PLWH were
      further investigated to evaluate if the exclusion was justified by scientific
      evidence. RESULTS: We identified 56 multicentre open clinical trials in lymphoma
      including 46 interventional trials. People living with HIV were excluded from 32
      interventional trials (70%). We identified a biologically valid reason (a
      potential increased risk of greater immunosuppression) for excluding PLWH from
      one trial and possibly for one optional arm in another study. CONCLUSIONS: There
      was no scientific or safety justification for excluding PLWH from most lymphoma
      clinical trials included on the NIHR portfolio. A clear justification for
      excluding PLWH was not offered in the available protocols. The exclusion of PLWH
      should be explicitly justified on scientific grounds in protocols to minimise
      stigmatisation.

PMID- 26313665
TI  - Stromal infiltration of CD8 T cells is associated with improved clinical outcome
      in HPV-positive oropharyngeal squamous carcinoma.
AB  - BACKGROUND: Patients with human papillomavirus (HPV)-positive oropharyngeal
      squamous cell carcinoma (OPSCC) have a better prognosis than those with HPV
      negative tumours. There is interest in de-escalating their treatment but
      strategies are needed for risk stratification to identify subsets with a poor
      prognosis. This study investigated tumour-infiltrating lymphocytes (TILs) in
      relation to HPV tumour status and patient survival. METHODS: Biopsies from 218
      patients diagnosed with OPSCC between 2002 and 2011, who underwent
      chemo/radiotherapy were analysed for HPV by PCR, in-situ hybridisation and p16
      immunohistochemistry (IHC). One hundred and thirty-nine samples with concordant
      HPV detection were analysed for CD3, CD4, CD8 and FoxP3 expression in tumour and
      stromal regions using multiplexIHC and multispectral image analysis. Labelling of
      smooth muscle actin (SMA) identified activated stroma. RESULTS: Human
      papillomavirus-positive compared with HPV-negative OPSCC had higher infiltration
      in both tumour and stromal areas of CD4 and CD8 T cells but not FoxP3 T
      regulatory cells. Only CD3+CD8+ stromal and not tumour area infiltration was
      associated with increased survival (P=0.02). There was significantly higher SMA
      expression in HPV-positive compared with -negative tumours, which did not
      correlate with survival. CONCLUSIONS: Studies of TILs for risk stratification in
      OPSCC should assess stromal infiltration.

PMID- 26313664
TI  - Baseline and lifetime alcohol consumption and risk of differentiated thyroid
      carcinoma in the EPIC study.
AB  - BACKGROUND: Results from several cohort and case-control studies suggest a
      protective association between current alcohol intake and risk of thyroid
      carcinoma, but the epidemiological evidence is not completely consistent and
      several questions remain unanswered. METHODS: The association between alcohol
      consumption at recruitment and over the lifetime and risk of differentiated
      thyroid carcinoma was examined in the European Prospective Investigation into
      Cancer and Nutrition. Among 477 263 eligible participants (70% women), 556 (90%
      women) were diagnosed with differentiated thyroid carcinoma over a mean follow-up
      of 11 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were
      estimated using multivariable Cox proportional hazards models. RESULTS: Compared
      with participants consuming 0.1-4.9 g of alcohol per day at recruitment,
      participants consuming 15 or more grams (approximately 1-1.5 drinks) had a 23%
      lower risk of differentiated thyroid carcinoma (HR=0.77; 95% CI=0.60-0.98). These
      findings did not differ greatly when analyses were conducted for lifetime alcohol
      consumption, although the risk estimates were attenuated and not statistically
      significant anymore. Similar results were observed by type of alcoholic beverage,
      by differentiated thyroid carcinoma histology or according to age, sex, smoking
      status, body mass index and diabetes. CONCLUSIONS: Our study provides some
      support to the hypothesis that moderate alcohol consumption may be associated
      with a lower risk of papillary and follicular thyroid carcinomas.

PMID- 26313667
TI  - Chronic Infection and Venous Thromboembolic Disease.
AB  - Venous thromboembolic disease often arises as a complication of another
      pathological condition and/or triggering event. Infectious diseases result from
      both the direct action of the pathogens themselves and their effect on the immune
      system. The resulting inflammatory process and the coagulation and fibrinolysis
      processes share common pathways, explaining why infection is associated with
      thrombosis. In this brief overview, besides certain chronic infectious diseases,
      we also consider some acute infections, as the mechanisms are likely to be
      similar, particularly in the initial infective stage or the more acute episodes
      of a chronic infection. The infectious agent can be viral, bacterial, fungal, or
      parasitic. However, the literature on the link between infections and venous
      thromboembolism (VTE) is uneven, favoring infections that are found in more
      developed countries where physicians have access to VTE diagnostic tools. Thus,
      large epidemiological studies in this field are restricted to a limited number of
      the common chronic infectious diseases such as tuberculosis, while for other
      infections, particularly parasitic and fungal infections, the link with VTE is
      only evoked in a few scattered case reports. 

PMID- 26313668
TI  - The World Needs More Jeannes.

PMID- 26313669
TI  - Prosopoplasty.

PMID- 26313670
TI  - Volunteering: Is It Really Worth It? You Bet It Is!

PMID- 26313671
TI  - Letter from the President of PSNCB.

PMID- 26313672
TI  - Enemies of Ethics Equals Environmental Exodus, Part 2.
AB  - Bullying and mobbing in the workplace have accelerated at alarming rates around
      the world in the past decade. Health care workers, nurses, managers, physicians,
      and owners of organizations, sometimes choose unethical methodology as a means to
      obtain personal and/or organizational goals. The consequences of these unethical
      decisions have a profound impact on the victim, bystanders, the organization, as
      well as the nursing profession. As a result, victims (nurses) often suffer from
      physiological and psychological distress, posttraumatic stress disorder, suicide,
      and erosion of professional confidence; patient's quality of care is undermined;
      nurses exit the profession; and organizations suffer from decreased morale,
      decline in productivity, financial loss, and a tarnished reputation.

PMID- 26313674
TI  - A Clinician-Guided Nonsurgical Cosmetic Patient Information Module: Preliminary
      Findings.
AB  - In 2011, nearly 13 million nonsurgical cosmetic procedures were performed,
      representing a 6% increase from the previous year. Patients often present with
      unrealistic treatment expectations based on beauty industry standards and
      misinformation. In addition, because of the lack of competency standardization in
      this area, providers frequently deliver inconsistent educational information to
      their patients. The initial goal of the project was to evaluate the clinician
      guided module, a 13-slide PowerPoint presentation that was disseminated to key
      stakeholders for preliminary review. A convenience sample of 10 women, aged 30-64
      years, was recruited. Following exposure to the module, each participant was
      asked to fill out an evaluation composed of both closed- and open-ended
      responses, noting her experience with this type of educational tool. Quantitative
      data were analyzed using comparison of means, whereas qualitative data were
      examined for the emergence of themes. Initial findings suggested that patients
      and health care providers found the clinician-guided module informative and
      visually appealing and that they would recommend this module to peers and
      colleagues. Potential social change from this project may surface through
      increased patient knowledge and empowerment, awareness, safety, and satisfaction.
      The final project will compare the clinician-guided patient information module to
      standard patient information evaluating treatment expectations of dermal fillers.
      The ultimate impact of a clinician-guided information module may improve
      standardization in this arena and thus be of particular interest to members of
      the nonsurgical cosmetic community. 

PMID- 26313675
TI  - Aesthetic Policy and Procedure Protocols: A "Must Have" for Every Aesthetic
      Medical Provider.
AB  - Treatment guidelines are a crucial part of every medical aesthetic practice and
      must be in place before utilizing aesthetic medical injectables. An "Aesthetic
      Policy and Procedure Manual" features specific details (e.g., patient assessment,
      indication, contraindications, warnings and precautions, injection techniques,
      documentation, etc.) around dermal fillers (e.g., Restylane, Juvederm, Voluma),
      hyaluronidase, neurotoxins (e.g., Botox Cosmetic, Dysport, and Xeomin) and
      Sculptra. This article describes why an "Aesthetic Policy and Procedure" manual
      is a necessary tool in every aesthetic provider's armamentarium, what it is
      composed of, as well as how these guidelines serve as a protective mechanism for
      the aesthetic provider's clinic if legal action is brought against their staff,
      their medical director, and/or their clinic. 

PMID- 26313676
TI  - Propranolol Use for Infantile Hemangiomas.

PMID- 26313677
TI  - A Review of the Use of Acellular Dermal Matrices in Postmastectomy Immediate
      Breast Reconstruction.
AB  - Acellular dermal matrices (ADMs) are now commonly used in postmastectomy implant
      based immediate breast reconstruction. In 2-stage reconstructions involving
      placement of a tissue expander followed by an implant, they can improve the
      aesthetic outcome and expedite the expansion process. The use of ADMs has also
      allowed for 1-stage immediate placement of an implant following mastectomy
      (direct-to-implant reconstruction). However, the use of ADMs is associated with
      an increased risk of certain types of complications. An understanding of the use
      of these materials is essential to the postoperative care of patients who undergo
      ADM-assisted breast reconstruction. In this article, the use of ADMs in
      postmastectomy immediate breast reconstruction is reviewed. 

PMID- 26313679
TI  - My Journey With Triple Negative Breast Cancer.

PMID- 26313680
TI  - Association between Weight Misperception Patterns and Depressive Symptoms in
      Korean Young Adolescents: National Cross-Sectional Study.
AB  - PURPOSE: Although distortion of weight perceptions has been known as a risk
      factor for adolescent depression, little has been known about the relationship
      between weight misperception patterns and depressive symptoms. This study
      explored the relationship between distortion of weight misperception patterns and
      depressive symptoms in Korean adolescents. METHODS: The subjects of this study
      were 109,373 middle school students who participated in the Korea Youth Risk
      Behavior Web-based Survey (KYRBWS) from 2011 to 2013. By comparing the difference
      between Body Mass Index (BMI) and subjective perceptions of body weight,
      misperceptions of weight were classified into two categories: misperception of
      underweight and misperception of overweight. RESULTS: When confounding variables
      were adjusted, the results of the logistic regression analysis revealed that male
      students who perceived themselves as underweight despite their normal weight were
      110% more likely to have depressive symptoms (OR = 1.10, 95% CI: 1.03-1.18) than
      male students with accurate weight perceptions. On the contrary, for female
      students, misperceptions of underweight had no significant relationship with
      depression symptoms. Regarding misperceptions of overweight, female students who
      perceived themselves as overweight despite their normal weight were 107% (OR =
      1.07, 95% CI: 1.02-1.11) more likely to have depressive symptoms than female
      students with accurate weight perceptions. Moreover, female students who
      perceived themselves as overweight when they were underweight were 137% (OR =
      1.37, 95% CI: 1.18-1.58) more likely to have depressive symptoms. CONCLUSION:
      Male students who underestimate their body weight and female students who
      overestimate their body weight were at a greater risk of depression emotions than
      students with accurate weight perceptions.

PMID- 26313681
TI  - Moyamoya disease presenting with subarachnoid hemorrhage: Clinical features and
      neuroimaging of a case series.
AB  - BACKGROUND: Hemorrhage is a major category of the clinical symptoms of moyamoya
      disease (MMD). Intracerebral and intraventricular hemorrhages are the most common
      hemorrhages in MMD, and subarachnoid hemorrhages (SAHs) are notably rare. There
      have only been a few previous case reports of this imaging manifestation. In the
      present study, we investigated the clinical and neuroimaging features of MMD
      patients who presented with SAH and sought to identify the possible causes of
      hemorrhage. METHODS: The right and left cerebral hemispheres of each patient were
      identified as hemorrhagic or non-hemorrhagic. Each hemisphere was assessed for
      Suzuki stage, and dilatation and branch extension of the anterior choroidal
      artery (AChA) and posterior communicating artery (P-CoM) and for the degree of
      transdural anastomosis and posterior circulation compensation. Next, these data
      were statistically analyzed for correlations with the SAH events. RESULTS: In 34
      of 349 hemorrhagic MMD patients, the first episode of hemorrhage was a SAH, among
      which, 26 (76.5%) patients were women and there was only one pediatric patient.
      The Suzuki stage was not statistically correlated with the SAH events. There were
      also no correlations between SAH and dilatation or abnormal branching of the AChA
      and P-CoM. In contrast, SAH and transdural anastomosis were correlated. 25 of the
      34 hemorrhagic hemispheres (73.5%) were positive for transdural anastomosis, and
      this number was 15 (44.1%) in the non-hemorrhagic hemispheres; this difference
      was statistically significant (P<0.05). CONCLUSIONS: SAH is an important type of
      hemorrhage in MMD patients and ranks as the fourth most common type after
      intracerebral hemorrhage (ICH), intraventricular hemorrhage (IVH), and ICH + IVH.
      It mainly occurs in adult women, and the rupture of the transdural anastomosis
      might be the main cause of this condition.

PMID- 26313682
TI  - Refining Prognosis in Lung Cancer: A Report on the Quality and Relevance of
      Clinical Prognostic Tools.
AB  - INTRODUCTION: Accurate, individualized prognostication for lung cancer patients
      requires the integration of standard patient and pathologic factors, biological,
      genetic, and other molecular characteristics of the tumor. Clinical prognostic
      tools aim to aggregate information on an individual patient to predict disease
      outcomes such as overall survival, but little is known about their clinical
      utility and accuracy in lung cancer. METHODS: A systematic search of the
      scientific literature for clinical prognostic tools in lung cancer published from
      January 1, 1996 to January 27, 2015 was performed. In addition, web-based
      resources were searched. A priori criteria determined by the Molecular Modellers
      Working Group of the American Joint Committee on Cancer were used to investigate
      the quality and usefulness of tools. Criteria included clinical presentation,
      model development approaches, validation strategies, and performance metrics.
      RESULTS: Thirty-two prognostic tools were identified. Patients with metastases
      were the most frequently considered population in non-small-cell lung cancer. All
      tools for small-cell lung cancer covered that entire patient population. Included
      prognostic factors varied considerably across tools. Internal validity was not
      formally evaluated for most tools and only 11 were evaluated for external
      validity. Two key considerations were highlighted for tool development:
      identification of an explicit purpose related to a relevant clinical population
      and clear decision points and prioritized inclusion of established prognostic
      factors over emerging factors. CONCLUSIONS: Prognostic tools will contribute more
      meaningfully to the practice of personalized medicine if better study design and
      analysis approaches are used in their development and validation.

PMID- 26313683
TI  - Postchemoradiotherapy Pathologic Stage Classified by the American Joint Committee
      on the Cancer Staging System Predicts Prognosis of Patients with Locally Advanced
      Esophageal Squamous Cell Carcinoma.
AB  - INTRODUCTION: To determine whether the postchemoradiotherapy (post-CRT)
      pathologic stage predicts the outcomes of patients with locally advanced
      esophageal squamous cell carcinoma (ESCC) undergoing preoperative CRT followed by
      surgery. METHODS: From three phase II trials of preoperative CRT for locally
      advanced ESCC, 140 patients were included. Preoperative CRT comprised twice
      weekly paclitaxel and cisplatin-based regimens and 40-Gy radiotherapy in 20
      fractions. The post-CRT pathologic stage was classified according to the American
      Joint Committee on Cancer, 7th edition staging system. The prognostic effects of
      clinicopathologic factors were analyzed using Cox regression. RESULTS: With a
      median follow-up of 61.9 months, the median progression-free survival (PFS) and
      overall survival (OS) of the entire cohort were 24.5 and 30.9 months,
      respectively. The post-CRT pathologic stage was 0 in 34.5%, I in 12.9%, II in
      29.3%, III in 13.6%, and ypT0N1-2 in 6.4% of the patients. The median PFS was
      47.2, 25.9, 16.0, 9.4, and 15.1 months, and the median OS was 57.4, 34.1, 26.2,
      14.1, and 17.6 months for patients with post-CRT pathologic stage 0, I, II, III,
      and ypT0N1-2, respectively. In multivariate analysis, performance status (p <
      0.001), tumor location (p = 0.016), and extranodal extension (p = 0.024) were
      independent prognostic factors for PFS, whereas performance status (p < 0.001)
      and post-CRT pathologic stage (p = 0.027) were independent prognostic factors for
      OS. CONCLUSIONS: The post-CRT pathologic stage classified by American Joint
      Committee on Cancer, 7th edition staging system predicted the survival of locally
      advanced ESCC patients who underwent preoperative paclitaxel and cisplatin-based
      CRT followed by esophagectomy.

PMID- 26313685
TI  - Sharing Research Data and Intellectual Property Law: A Primer.
AB  - Sharing research data by depositing it in connection with a published article or
      otherwise making data publicly available sometimes raises intellectual property
      questions in the minds of depositing researchers, their employers, their funders,
      and other researchers who seek to reuse research data. In this context or in the
      drafting of data management plans, common questions are (1) what are the legal
      rights in data; (2) who has these rights; and (3) how does one with these rights
      use them to share data in a way that permits or encourages productive downstream
      uses? Leaving to the side privacy and national security laws that regulate
      sharing certain types of data, this Perspective explains how to work through the
      general intellectual property and contractual issues for all research data. 

PMID- 26313684
TI  - Pattern of Failure Analysis in Metastatic EGFR-Mutant Lung Cancer Treated with
      Tyrosine Kinase Inhibitors to Identify Candidates for Consolidation Stereotactic
      Body Radiation Therapy.
AB  - INTRODUCTION: The role of stereotactic body radiation therapy (SBRT) in patients
      with metastatic lung cancer harboring epidermal growth factor receptor (EGFR)
      mutations is not defined. We evaluated the pattern of failure in patients
      receiving tyrosine kinase inhibitor (TKI) therapy to identify candidates for
      consolidation SBRT. METHODS: Computed tomography scans were reviewed in a cohort
      of EGFR-mutant patients enrolled on prospective TKI trials. Initial progression
      in sites of original disease (primary/metastatic) or new sites was classified as
      original site failure (OF) or distant site failure (DF), respectively.
      Simultaneous OF/DF was labeled ODF. Disease characteristics were analyzed for
      associations with patterns of failure using actuarial competing risks
      methodology. RESULTS: Complete serial imaging was available in 49 patients with
      measurable disease. Median time to any progression was 8.3 months. The majority
      failed initially in original disease sites with OF, ODF, and DF frequencies being
      47.0%, 32.6%, and 20.4%, respectively. Primary tumor size was the most
      significant predictor of OF in univariate and multivariate analysis (p = 0.004).
      Median time to progression was 3 months shorter in patients with OF compared with
      DF. Ten patients (20%) were retroactively classified as consolidation SBRT
      candidates based on the extent of disease at time of best response to TKI
      therapy, and in seven of these, initial progression occurred in original tumor
      sites. CONCLUSION: Initial progression of TKI-treated cancers occurred
      predominantly in original disease sites. Consolidation SBRT was judged feasible
      in a subset of patients following maximum TKI response and may have prevented
      oligoprogression in most of these. In addition, we hypothesize that consolidation
      SBRT for residual disease could delay subsequent metastatic reseeding.

PMID- 26313686
TI  - Macular Vascular Abnormalities Identified by Optical Coherence Tomographic
      Angiography in Patients With Sickle Cell Disease.
AB  - IMPORTANCE: Patients with sickle cell disease may develop various macular
      vascular abnormalities that have not been described previously and can be seen
      using optical coherence tomographic angiography. OBSERVATIONS: Ten eyes from 5
      consecutive patients (3 men and 2 women) with sickle cell disease (4 patients
      with hemoglobin SS disease and 1 patient with hemoglobin SC disease) were
      included. The mean age was 37.6 years. Five of 10 eyes (50%) had retinal thinning
      that was identified using spectral-domain optical coherence tomography. Each of
      these eyes had corresponding loss of vascular density in the superficial or deep
      retinal plexus (or both). CONCLUSIONS AND RELEVANCE: Optical coherence
      tomographic angiography provides a novel way to view the retinal vasculature,
      including the superficial and deep capillary plexus, and may provide a sensitive
      method for identifying macular vascular abnormalities in patients with sickle
      cell disease.

PMID- 26313688
TI  - Tumor necrosis factor-alpha induced protein 6 attenuates acute lung injury
      following paraquat exposure.
AB  - CONTEXT: Paraquat exposure commonly occurs in the developing countries and the
      mortality rate is high. However, there is currently no consensus on the efficacy
      of treatment for paraquat exposure. OBJECTIVE: The study was aimed to explore the
      effects of tumor necrosis factor-alpha (TNF-alpha) induced protein 6 (TSG-6) on
      acute lung injury (ALI) following paraquat exposure in rats. MATERIALS AND
      METHODS: Male Sprague-Dawley (SD) rats were randomly divided into the sham group
      (n = 8), the paraquat group (n = 8), and the paraquat TSG-6-treated group (n =
      8). Rats were administered with 50 mg/kg of paraquat intraperitoneally. At 1 h
      after exposure, rats were treated with 30 MUg of recombinant human TSG-6 (rhTSG
      6) intraperitoneally. After 6 h of exposure, ALI scores were evaluated by
      histology and the expression of pro-inflammatory cytokines in lung was assayed
      using real-time RT-PCR. RESULTS: ALI scores were significantly lower in the
      paraquat TSG-6-treated group, compared with the paraquat group (p < 0.05). The
      expression of interleukin (IL)-1beta, IL-6, and TNF-alpha mRNA was significantly
      lower in the paraquat TSG-6-treated group, compared with the paraquat group (p <
      0.01, respectively). DISCUSSION AND CONCLUSION: Administration of rhTSG-6
      attenuates ALI following paraquat exposure by suppressing inflammatory response.

PMID- 26313689
TI  - Large-Scale Variations in Lumber Value Recovery of Yellow Birch and Sugar Maple
      in Quebec, Canada.
AB  - Silvicultural restoration measures have been implemented in the northern
      hardwoods forests of southern Quebec, Canada, but their financial applicability
      is often hampered by the depleted state of the resource. To help identify sites
      most suited for the production of high quality timber, where the potential return
      on silvicultural investments should be the highest, this study assessed the
      impact of stand and site characteristics on timber quality in sugar maple (Acer
      saccharum Marsh.) and yellow birch (Betula alleghaniensis Britt.). For this
      purpose, lumber value recovery (LVR), an estimate of the summed value of boards
      contained in a unit volume of round wood, was used as an indicator of timber
      quality. Predictions of LVR were made for yellow birch and sugar maple trees
      contained in a network of more than 22000 temporary sample plots across the
      Province. Next, stand-level variables were selected and models to predict LVR
      were built using the boosted regression trees method. Finally, the occurrence of
      spatial clusters was verified by a hotspot analysis. Results showed that in both
      species LVR was positively correlated with the stand age and structural diversity
      index, and negatively correlated with the number of merchantable stems. Yellow
      birch had higher LVR in areas with shallower soils, whereas sugar maple had
      higher LVR in regions with deeper soils. The hotspot analysis indicated that
      clusters of high and low LVR exist across the province for both species. Although
      it remains uncertain to what extent the variability of LVR may result from
      variations in past management practices or in inherent site quality, we argue
      that efforts to produce high quality timber should be prioritized in sites where
      LVR is predicted to be the highest. 

PMID- 26313687
TI  - Characterization of the Transcriptome of the Xerophyte Ammopiptanthus mongolicus
      Leaves under Drought Stress by 454 Pyrosequencing.
AB  - BACKGROUND: Ammopiptanthus mongolicus (Maxim. Ex Kom.) Cheng f., an endangered
      ancient legume species, endemic to the Gobi desert in north-western China. As the
      only evergreen broadleaf shrub in this area, A. mongolicus plays an important
      role in the region's ecological-environmental stability. Despite the strong
      potential of A. mongolicus in providing new insights on drought tolerance,
      sequence information on the species in public databases remains scarce. To both
      learn about the role of gene expression in drought stress tolerance in A.
      mongolicus and to expand genomic resources for the species, transcriptome
      sequencing of stress-treated A. mongolicus plants was performed. RESULTS: Using
      454 pyrosequencing technology, 8,480 and 7,474 contigs were generated after de
      novo assembly of RNA sequences from leaves of untreated and drought-treated
      plants, respectively. After clustering using TGICL and CAP3 programs, a combined
      assembly of all reads produced a total of 11,357 putative unique transcripts
      (PUTs). Functional annotation and classification of the transcripts were
      conducted by aligning the 11,357 PUTs against the public protein databases and
      nucleotide database (Nt). Between control and drought-treated plants, 1,620
      differentially expressed genes (DEGs) were identified, of which 1,106 were up
      regulated and 514 were down-regulated. The differential expression of twenty
      candidate genes in metabolic pathways and transcription factors families related
      to stress-response were confirmed by quantitative real-time PCR. Representatives
      of several large gene families, such as WRKY and P5CS, were identified and
      verified in A. mongolicus for the first time. CONCLUSIONS: The additional
      transcriptome resources, gene expression profiles, functional annotations, and
      candidate genes provide a more comprehensive understanding of the stress response
      pathways in xeric-adapted plant species such as A. mongolicus.

PMID- 26313690
TI  - The Role of Patient Activation in Preferences for Shared Decision Making: Results
      From a National Survey of U.S. Adults.
AB  - Studies investigating preferences for shared decision making (SDM) have focused
      on associations with sociodemographic variables, with few investigations
      exploring patient factors. We aimed to investigate the relationship between
      patient activation and preferences for SDM in 6 common medical decisions among a
      nationally representative cross-sectional survey of American adults. Adults older
      than 18 were recruited online (n = 2,700) and by telephone (n = 700). Respondents
      completed sociodemographic assessments and the Patient Activation Measure. They
      were also asked whether they perceived benefit (yes/no) in SDM in 6 common
      medical decisions. Nearly half of the sample (45.9%) reached the highest level of
      activation (Level 4). Activation was associated with age (p < .001), higher
      income (p = .001), higher education (p = .010), better self-rated health (p <
      .001), and fewer chronic conditions (p = .050). The proportion of people who
      agreed that SDM was beneficial varied from 53.1% (deciding the necessity of a
      diagnostic test) to 71.8% (decisions associated with making lifestyle changes).
      After we controlled for participant characteristics, higher activation was
      associated with greater perceived benefit in SDM across 4 of the 6 decisions.
      Preferences for SDM varied among 6 common medical scenarios. Low patient
      activation is an important barrier to SDM that could be ameliorated through the
      development of behavioral interventions.

PMID- 26313691
TI  - Metagenomic Analysis of Crohn's Disease Patients Identifies Changes in the Virome
      and Microbiome Related to Disease Status and Therapy, and Detects Potential
      Interactions and Biomarkers.
AB  - BACKGROUND: The aim of this study was to survey the bacterial and viral
      communities in different types of samples from patients with Crohn's disease (CD)
      at different stages of the disease to relate their distribution with the origin
      and progression of this disorder. METHODS: A total of 42 fecal samples and 15
      biopsies from 20 patients with CD and 20 healthy control individuals were
      collected for bacterial 16S rRNA gene profiling and DNA/RNA virome metagenomic
      analysis through 454 pyrosequencing. Their composition, abundance, and diversity
      were analyzed, and comparisons of disease status, patient status, and sample
      origin were used to determine statistical differences between the groups.
      RESULTS: Bacterial composition and relative abundance in new-onset patients with
      CD differed markedly from control individuals. Individual variability and sample
      origin had a stronger impact on viral communities than the disease, contrary to
      what was observed for bacterial populations although increased numbers of
      overrepresented viruses were observed in feces from patients with CD. Correlation
      based networks were constructed to show potential relations between bacteria and
      between those and viruses. CONCLUSIONS: The bacterial community reflects the
      disease status of individuals more accurately than their viral counterparts.
      However, numerous viral biomarkers specifically associated with CD disease were
      identified. Because viruses can modulate bacterial communities, the correlation
      networks between both communities constitute a step forward in unraveling their
      interactions under normal and CD disease conditions.

PMID- 26313692
TI  - Strong Upregulation of AIM2 and IFI16 Inflammasomes in the Mucosa of Patients
      with Active Inflammatory Bowel Disease.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is characterized by a chronic
      inflammation of the gut, partly driven by defects in the innate immune system.
      Considering the central role of inflammasome signaling in innate immunity, we
      studied inflammasome components in IBD mucosa. METHODS: Expression of genes
      encoding inflammasome sensor subunits was investigated in colonic mucosal
      biopsies from 2 cohorts of patients with IBD and controls. RESULTS: A significant
      upregulation (>2-fold change in expression, false discovery rate <0.05) of the
      PYHIN inflammasomes AIM2 and IFI16 in active IBD versus controls was found. Also
      IFI16 was significantly increased in inactive IBD versus controls. Moreover,
      responders to anti-tumor necrosis factor therapy showed decreased expression of
      these inflammasomes although IFI16 remained significantly increased in responders
      showing endoscopic healing versus controls. AIM2 was mainly expressed in
      epithelial cells, whereas IFI16 was expressed in both lymphocytes and epithelial
      cells. Functional activation of predominant AIM2/IFI16-mediated inflammasomes in
      active IBD colon was shown by the presence of the downstream effectors CASP1 and
      HMGB-1 in inflamed mucosa. CONCLUSIONS: Our results highlight the importance of
      PYHIN inflammasome signaling in IBD and also link anti-tumor necrosis factor
      responsiveness to inflammasome signaling. Together, this points to the potential
      value of the inflammasome pathway as a new therapeutic target for IBD treatment.

PMID- 26313693
TI  - Adherence to Rectal Mesalamine in Patients with Ulcerative Colitis.
AB  - BACKGROUND: Rectal mesalamine is an effective induction and maintenance therapy
      for ulcerative colitis. Little is known about the adherence rates to rectal
      mesalamine or barriers to its use. The aim was to quantify the prevalence of
      nonadherence to rectal mesalamine and to identify patient-reported barriers to
      adherence. METHODS: A cohort of patients with ulcerative colitis was
      prospectively enrolled in this observational study and followed for 12 months.
      Adherence was assessed by tracking pharmacy refills (medication possession
      ratio). Individual interviews were undertaken in a subset of subjects.
      Transcripts from the focus groups and interviews were analyzed to identify themes
      and links between these themes using qualitative data software (MaxQDA). RESULTS:
      Seventy patients prescribed rectal mesalamine were prospectively enrolled in the
      study. At enrollment, 39 of 70 subjects (55%) self-reported "occasional
      nonadherence" to rectal mesalamine. Over the 12-month follow-up period, only 20
      subjects (26%) completed 3 or more refills. Males, or subjects prescribed a once
      a-day suppository, were significantly more likely to refill than females (odds
      ratio = 3.3, 95% confidence interval, 1.1-10.9) or those prescribed suppositories
      more than once a day (odds ratio = 1.3, 95% confidence interval, 1.1-1.7). By
      medication possession ratio criteria, 71% of all subjects were nonadherent with
      their prescribed regimen (medication possession ratio <0.6). Nonadherers were
      significantly older than adherent subjects: mean age 48 years in nonadherers,
      versus 37 in adherers, P = 0.04. Patients who were nonadherent to rectal
      mesalamine frequently cited the mode of administration (65%) and busy lifestyle
      (40%) as reasons for nonadherence. CONCLUSIONS: Intentional nonadherence is
      common in patients who have been prescribed rectal mesalamine. Gender, age,
      frequency of dosing, and lifestyle factors may impact adherence.

PMID- 26313695
TI  - Assessment of Circulating MicroRNAs for the Diagnosis and Disease Activity
      Evaluation in Patients with Ulcerative Colitis by Using the Nanostring
      Technology.
AB  - BACKGROUND: Clinical decision and patient care management in inflammatory bowel
      diseases is largely based on the assessment of clinical symptoms, while the
      biomarkers currently in use poorly reflect the actual disease activity.
      Therefore, the identification of novel biomarkers will serve an unmet clinical
      need for IBD screening and patient management. We examined the utility of
      circulating microRNAs for diagnosis and disease activity monitoring in patients
      with ulcerative colitis (UC). METHODS: Blood serum microRNAs were isolated from
      patients with UC with active and inactive disease and healthy donors. High
      throughput microRNA profiling was performed using the Nanostring technology
      platform. Clinical disease activity was captured by calculating the partial Mayo
      score. C-reactive protein was measured in patients with UC as part of their
      clinical monitoring. The profiles of circulating microRNAs and C-reactive protein
      were correlated with clinical disease indices. RESULTS: We have identified a
      signature of 12 circulating microRNAs that differentiate patients with UC from
      control subjects. Moreover, 6 of these microRNAs significantly correlated with UC
      disease activity. Importantly, a set of 4 microRNAs (hsa-miR-4454, hsa-miR-223
      3p, hsa-miR-23a-3p, and hsa-miR-320e), which correlated with UC disease activity
      were found to have higher sensitivity and specificity values than C-reactive
      protein. CONCLUSIONS: Circulating microRNAs provide a novel diagnostic and
      prognostic marker for patients with UC. The use of an FDA-approved platform could
      accelerate the application of microRNA screening in a gastrointenstinal clinical
      setting. When used in combination with current diagnostic and disease activity
      assessment modalities, microRNAs could improve both IBD screening and care
      management.

PMID- 26313694
TI  - IL-33 Signaling Protects from Murine Oxazolone Colitis by Supporting Intestinal
      Epithelial Function.
AB  - BACKGROUND: IL-33, a member of the IL-1 cytokine family that signals through ST2,
      is upregulated in ulcerative colitis (UC); however, the role of IL-33 in colitis
      remains unclear. IL-33 augments type 2 immune responses, which have been
      implicated in UC pathogenesis. We sought to determine the role of IL-33 signaling
      in oxazolone (OXA) colitis, a type 2 cytokine-mediated murine model of UC.
      METHODS: Colon mucosal IL-33 expression was compared between pediatric and adult
      UC and non-IBD patients using immunohistochemistry and real-time PCR. OXA colitis
      was induced in WT, IL-33, and ST2 mice, and histopathology, cytokine levels, and
      goblet cells were assessed. Transepithelial resistance was measured across IL-33
      treated T84 cell monolayers. RESULTS: Colon mucosal IL-33 was increased in
      pediatric patients with active UC and in OXA colitis. IL-33 and ST2 OXA mice
      exhibited increased disease severity compared with WT OXA mice. OXA induced a
      mixed mucosal cytokine response, but few differences were observed between OXA WT
      and IL-33 or ST2 mice. Goblet cells were significantly decreased in IL-33 and ST2
      OXA compared with WT OXA mice. IL-33 augmented transepithelial resistance in T84
      cells, and this effect was blocked by the ERK1/2 inhibitor PD98,059. CONCLUSIONS:
      OXA colitis is exacerbated in IL-33 and ST2 mice. Increased mucosal IL-33 in
      human UC and murine colitis may be a homeostatic response to limit inflammation,
      potentially through effects on epithelial barrier function. Further investigation
      of IL-33 protective mechanisms would inform the development of novel therapeutic
      approaches.

PMID- 26313696
TI  - The Occurrence of Thrombosis in Inflammatory Bowel Disease Is Reflected in the
      Clot Lysis Profile.
AB  - BACKGROUND: The occurrence of thromboembolic events (TE) is an important
      extraintestinal manifestation in patients with inflammatory bowel disease (IBD).
      The aim of this study was to compare fibrinolysis and clot lysis parameters
      between (1) patients with IBD and healthy controls and (2) patients with IBD with
      TE (IBD + TE) and without TE (IBD - TE). METHODS: One hundred thirteen healthy
      controls and 202 patients with IBD, of which 84 patients with IBD + TE and 118
      patients with IBD - TE, were included in this case-control study. Three clot
      lysis parameters (area under the curve, 50% clot lysis time, and amplitude) were
      determined using a clot lysis assay. Plasminogen activator inhibitor 1 (PAI-1)
      and thrombin activatable fibrinolysis inhibitor concentrations were determined by
      enzyme-linked immunosorbent assay. RESULTS: PAI-1 antigen, active PAI-1, and
      intact thrombin activatable fibrinolysis inhibitor concentrations, as well as 50%
      clot lysis time and area under the curve, were significantly associated with the
      presence of IBD (all P < 0.05). The median time between TE and plasma collection
      was 5.0 (1.8-11.0) years. Comparing IBD + TE versus IBD - TE, active to total PAI
      1 ratio (0.36 [0.24-0.61] versus 0.24 [0.13-0.40]), area under the curve (31 [24
      49] versus 22 [13-31]), 50% clot lysis time (110 [64-132] versus 95 [70-126]
      minutes), and amplitude (0.295 [0.222-0.436] versus 0.241 [0.168-0.308]) were
      significantly higher in IBD + TE (all P <0.05) and remained higher after
      adjustment for age, gender, C-reactive protein, type of disease, presence of
      comorbidities, and disease activity. CONCLUSIONS: Patients with IBD have an
      altered clot lysis profile compared with healthy controls. Clot lysis parameters
      differ significantly between patients with IBD with and without a history of TE
      and should be included in the risk assessment.

PMID- 26313697
TI  - Efficacy, tolerability and impact on quality of life of clindamycin phosphate and
      benzoyl peroxide for the treatment of cetuximab-associated acneiform eruption in
      patients with metastatic colorectal cancer.
AB  - BACKGROUND: Epidermal growth factor receptor inhibitors are recent antineoplastic
      treatments used for the treatment of some non-cutaneous tumours, which aberrantly
      express EGFR. Because of their specificity, these drugs have low systemic
      toxicity, but frequent undesired cutaneous effects, the most common of which is
      an acneiform eruption, occurring after 1-3 weeks of treatment. Management of this
      rash is not well standardized. OBJECTIVE: We evaluated efficacy, tolerability and
      impact on quality of life of a clindamycin phosphate 1.2%-benzoyl peroxide 5% gel
      in 12 male adults who developed acneiform eruption during treatment with
      cetuximab for metastatic colorectal cancer. METHODS: Patients applied the
      clindamycin phosphate-benzoyl peroxide gel once daily, at evening, for 8 weeks.
      The Skin-Score was used to evaluate reduction of erythema, papules, pustules and
      pruritus, the Dermatology Life Quality Index questionnaire to evaluate the
      improvements of health-related quality of life. RESULTS: Significant clinical
      improvements occurred after 2 weeks of treatment and were even more evident after
      8 weeks (mean Skin-Score 20.54 +/- 7.83, p = 1.37 * 10(-6) vs. second week visit,
      p = 1.26 * 10(-7) vs. before treatment). Accordingly, DLQI values decreased from
      13.64 +/- 2.01 before treatment to 6.45 +/- 1.37 after 8 weeks (p = 1.12 * 10(
      5)). CONCLUSION: A clindamycin phosphate-benzoyl peroxide gel may be an effective
      and safe option in the treatment of cetuximab-associated acneiform eruptions.

PMID- 26313698
TI  - Epigenetic regulation of iron homeostasis in Arabidopsis.
AB  - Iron (Fe) is one of the most important microelement required for plant growth and
      development because of its unique property of catalyzing oxidation/reduction
      reactions. Iron deficiency impairs fundamental processes which could lead to a
      decrease in chlorophyll production and pollen fertility, thus influencing crop
      productivity and quality. However, iron in excess is toxic to the cell and is
      harmful to the plant. To exactly control the iron content in all tissues, plants
      have evolved many strategies to regulate iron homeostasis, which refers to 2
      successive steps: iron uptake at the root surface, and iron distribution in vivo.
      In the last decades, a number of transporters and regulatory factors involved in
      this process have been isolated and identified. To cope with the complicated
      flexible environmental conditions, plants apply diverse mechanisms to regulate
      the expression and activity of these components. One of the most important
      mechanisms is epigenetic regulation of iron homeostasis. This review has been
      presented to provide an update on the information supporting the involvement of
      histone modifications in iron homeostasis and possible future course of the
      field. 

PMID- 26313699
TI  - Assessment of dietary vitamin A intake (retinol, alpha-carotene, beta-carotene,
      beta-cryptoxanthin) and its sources in the National Survey of Dietary Intake in
      Spain (2009-2010).
AB  - The aim of this study is to assess the intake of the individual components of
      vitamin A and major dietary sources in the Spaniards using data on food
      consumption from Spanish National Dietary Intake Survey (2009-2010). A 24-h
      dietary recall, 3-day diet diary and a software application that includes HPLC
      analytical data were used. Average dietary vitamin A intake is 716.4 ug retinol
      equivalents (RE), which is supplied as retinol (57.9%RE) and as provitamin-A
      carotenoids (42.1%RE). beta-Carotene represents 71.9% of provitamin-A
      carotenoids, beta-cryptoxanthin 15.3%, alpha-carotene 12.8%. Red- and orange
      colored fruits and vegetables are major contributors of provitamin-A (1587
      ug/day). Spanish diet covers the dietary reference on the intake for vitamin A,
      provided mainly by foods of animal origin. The main contributors to the intake of
      provitamin-A carotenoids are carrots, tomatoes, spinach and oranges. Data on the
      intake of individual components of vitamin A contribute to improving our
      understanding of the relationship between diet and health. 

PMID- 26313700
TI  - Situational judgement tests in medical education and training: Research, theory
      and practice: AMEE Guide No. 100.
AB  - Why use SJTs? Traditionally, selection into medical education professions has
      focused primarily upon academic ability alone. This approach has been questioned
      more recently, as although academic attainment predicts performance early in
      training, research shows it has less predictive power for demonstrating
      competence in postgraduate clinical practice. Such evidence, coupled with an
      increasing focus on individuals working in healthcare roles displaying the core
      values of compassionate care, benevolence and respect, illustrates that
      individuals should be selected on attributes other than academic ability alone.
      Moreover, there are mounting calls to widen access to medicine, to ensure that
      selection methods do not unfairly disadvantage individuals from specific groups
      (e.g. regarding ethnicity or socio-economic status), so that the future workforce
      adequately represents society as a whole. These drivers necessitate a method of
      assessment that allows individuals to be selected on important non-academic
      attributes that are desirable in healthcare professionals, in a fair, reliable
      and valid way. What are SJTs? Situational judgement tests (SJTs) are tests used
      to assess individuals' reactions to a number of hypothetical role-relevant
      scenarios, which reflect situations candidates are likely to encounter in the
      target role. These scenarios are based on a detailed analysis of the role and
      should be developed in collaboration with subject matter experts, in order to
      accurately assess the key attributes that are associated with competent
      performance. From a theoretical perspective, SJTs are believed to measure
      prosocial Implicit Trait Policies (ITPs), which are shaped by socialisation
      processes that teach the utility of expressing certain traits in different
      settings such as agreeable expressions (e.g. helping others in need), or
      disagreeable actions (e.g. advancing ones own interest at others, expense). Are
      SJTs reliable, valid and fair? Several studies, including good quality meta
      analytic and longitudinal research, consistently show that SJTs used in many
      different occupational groups are reliable and valid. Although there is over 40
      years of research evidence available on SJTs, it is only within the past 10 years
      that SJTs have been used for recruitment into medicine. Specifically, evidence
      consistently shows that SJTs used in medical selection have good reliability, and
      predict performance across a range of medical professions, including performance
      in general practice, in early years (foundation training as a junior doctor) and
      for medical school admissions. In addition, SJTs have been found to have
      significant added value (incremental validity) over and above other selection
      methods such as knowledge tests, measures of cognitive ability, personality tests
      and application forms. Regarding differential attainment, generally SJTs have
      been found to have lower adverse impact compared to other selection methods, such
      as cognitive ability tests. SJTs have the benefit of being appropriate both for
      use in selection where candidates are novices (i.e. have no prior role experience
      or knowledge such as in medical school admissions) as well as settings where
      candidates have substantial job knowledge and specific experience (as in
      postgraduate recruitment for more senior roles). An SJT specification (e.g.
      scenario content, response instructions and format) may differ depending on the
      level of job knowledge required. Research consistently shows that SJTs are
      usually found to be positively received by candidates compared to other selection
      tests such as cognitive ability and personality tests. Practically, SJTs are
      difficult to design effectively, and significant expertise is required to build a
      reliable and valid SJT. Once designed however, SJTs are cost efficient to
      administer to large numbers of candidates compared to other tests of non-academic
      attributes (e.g. personal statements, structured interviews), as they are
      standardised and can be computer-delivered and machine-marked.

PMID- 26313701
TI  - Challenges in the care of familial hypercholesterolemia: a community care
      perspective.
AB  - Familial hyperchoelsterolaemia (FH) remains under-diagnosed and under-treated in
      the community setting. Earlier evidence suggested a prevalence of 1:500 worldwide
      but newer evidence suggests it is more common. Less than 15% of FH patients are
      ever diagnosed, with children and young adults rarely tested despite having the
      most to gain given their lifetime exposure. Increasing awareness among primary
      care teams is critical to improve the detection profile for FH. Cascade testing
      in the community setting needs a sustainable approach to be developed to
      facilitate family tracing of index cases. The use of the Dutch Lipid Clinic
      Network Criteria score to facilitate a phenotypic diagnosis is the preferred
      approach adopted in Australia and eliminates the need to undertake genetic
      testing for all suspected FH cases. 

PMID- 26313702
TI  - Ion segregation in an ionic liquid confined within chitosan based chemical
      ionogels.
AB  - Ionogels based on in situ crosslinking of chitosan in the ionic liquid 1-ethyl-3
      methylimidazolium acetate (EMIm Ac) are synthesized, and studied from macroscopic
      properties to preferred interactions at the host matrix/EMIm Ac interface. It is
      highlighted that the imidazolium cations of the ionic liquid (IL) show preferred
      interactions with the chitosan host matrix. This exemplifies how the confinement
      of ILs, through an interface effect, can induce the breakdown of aggregated
      regions found systematically in bulk ILs and can increase the fragility of ILs.
      These biopolymer based ionogels could find application as biosensors and in the
      field of energy. 

PMID- 26313703
TI  - Exposure assessment issues in epidemiology studies of phthalates.
AB  - PURPOSE: The purpose of this paper is to review exposure assessment issues that
      need to be addressed in designing and interpreting epidemiology studies of
      phthalates, a class of chemicals commonly used in consumer and personal care
      products. Specific issues include population trends in exposure, temporal
      reliability of a urinary metabolite measurement, and how well a single urine
      sample may represent longer-term exposure. The focus of this review is on seven
      specific phthalates: diethyl phthalate (DEP); di-n-butyl phthalate (DBP);
      diisobutyl phthalate (DiBP); butyl benzyl phthalate (BBzP); di(2-ethylhexyl)
      phthalate (DEHP); diisononyl phthalate (DiNP); and diisodecyl phthalate (DiDP).
      METHODS: Comprehensive literature search using multiple search strategies.
      RESULTS: Since 2001, declines in population exposure to DEP, BBzP, DBP, and DEHP
      have been reported in the United States and Germany, but DEHP exposure has
      increased in China. Although the half-lives of various phthalate metabolites are
      relatively short (3 to 18h), the intraclass correlation coefficients (ICCs) for
      phthalate metabolites, based on spot and first morning urine samples collected
      over a week to several months, range from weak to moderate, with a tendency
      toward higher ICCs (greater temporal stability) for metabolites of the shorter
      chained (DEP, DBP, DiBP and BBzP, ICCs generally 0.3 to 0.6) compared with those
      of the longer-chained (DEHP, DiNP, DiDP, ICCs generally 0.1 to 0.3) phthalates.
      Additional research on optimal approaches to addressing the issue of urine
      dilution in studies of associations between biomarkers and different type of
      health effects is needed. CONCLUSIONS: In conclusion, the measurement of urinary
      metabolite concentrations in urine could serve as a valuable approach to
      estimating exposure to phthalates in environmental epidemiology studies. Careful
      consideration of the strengths and limitations of this approach when interpreting
      study results is required.

PMID- 26313704
TI  - Confidence interval estimation for pooled-sample biomonitoring from a complex
      survey design.
AB  - The National Centers for Disease Control and Prevention (CDC) is using a weighted
      pooled-sample design to characterize concentrations of persistent organic
      pollutants (POPs) in the U.S. POPULATION: Historically, this characterization has
      been based on individual measurements of these compounds in body fluid or tissue
      from representative samples of the population using stratified multistage
      selection. Pooling samples before making analytical measurements reduces the
      costs of biomonitoring by reducing the number of analyses. Pooling samples also
      allows for larger sample volumes which can result in fewer left censored results.
      But because samples are pooled across the sampling design cells of the original
      survey, direct calculation of the design effects needed for accurate standard
      error and confidence interval (CI) estimation is not possible. So in this paper I
      describe a multiple imputation (MI) method for calculating design effects
      associated with pooled-sample estimates. I also evaluate the method presented, by
      simulating NHANES individual sample data from which artificial pools are created
      for use in a comparison of pooled-sample estimates with estimates based on
      individual samples. To further illustrate and evaluate the method proposed in
      this paper I present geometric mean and various percentile estimates along with
      their 95% CIs for two chemical compounds from NHANES 2005-2006 pooled samples and
      compare them to individual-sample based estimates from NHANES 1999-2004.

PMID- 26313706
TI  - Drug-Related-Problem Outcomes and Program Satisfaction from a Comprehensive Brown
      Bag Medication Review.
AB  - OBJECTIVES: To classify and quantify drug-related problems (DRPs), determine
      acceptance of DRP recommendations, and assess medication review satisfaction.
      DESIGN: Comprehensive brown bag medication reviews. SETTING: Six senior centers
      and three senior high-rises. PARTICIPANTS: Individuals aged 60 and older (mean
      age 75.9 +/- 8.5) taking five or more medications (n = 85). MEASUREMENTS: Two
      investigators independently classified DRPs using modified Pharmaceutical Care
      Network Europe classification scheme and severity of medication error and value
      of service scales. Two other investigators adjudicated classification
      differences. Satisfaction surveys were administered immediately and 3 months
      after review. A DRP recommendation implementation survey was completed at least 3
      months after the review. RESULTS: Participants had a mean of 4.3 +/- 2.8 DRPs
      (range 0-10). DRPs were classified as adverse reactions (30%), treatment
      effectiveness (28%), treatment costs (13%), information need (8%), and other
      (21%). Causes included drug selection (40%), wrong dosage (23%), participant
      problems (e.g., adherence, lack of medication knowledge, 16%), drug use process
      problems (12%), drug formulation (0.5%), treatment duration (0.5%), and other
      (7%). Interventions required drug changes (44%), prescriber input (37%),
      individual counseling (18%), or other (1%). DRP severities were significant (59%)
      or minor (35%). Participants expressed satisfaction with the program because they
      were able to ask questions, trusted the answers, and knew more about their
      medications. After 3 months, they had implemented 63% of the DRP recommendations.
      CONCLUSION: Older adults found the medication review helpful and implemented 63%
      of the DRP recommendations.

PMID- 26313705
TI  - Sestrin2 facilitates death receptor-induced apoptosis in lung adenocarcinoma
      cells through regulation of XIAP degradation.
AB  - Apoptosis plays a critical physiological role in controlling cell number and
      eliminating damaged, non-functional and transformed cells. Cancerous cells as
      well as some types of normal cells are often resistant to cell death induced by
      pro-inflammatory cytokines through death receptors. This potentially allows
      cancer cells to evade the control from the immune system and to proceed toward a
      more malignant stage, although the mechanisms of this evasion are not well
      established. We have recently identified the stress-responsive Sestrin2 protein
      as a critical regulator of cell viability under stress conditions. Sestrin2 is a
      member of a small family of antioxidant proteins and inhibitors of mechanistic
      Target of Rapamycin Complex 1 (mTORC1) kinase. Down-regulation of Sestrin1/2
      leads to genetic instability and accelerates the growth of lung adenocarcinoma
      xenografts. Here we addressed the potential role of Sestrin2 in regulation of
      cell death induced by TNFR1 and related Fas and TRAIL receptors in lung
      adenocarcinoma cells. We found that Sestrin2 silencing strongly inhibits cytokine
      induced cell death through a mechanism independent of ROS and mTORC1 regulation.
      We determined that the X-linked inhibitor of apoptosis protein (XIAP) plays a
      critical role in the control of cytokine-induced cell death by Sestrin2. Thus our
      study defines a new, previously unrecognized role of Sestrin2 in the regulation
      of apoptosis. 

PMID- 26313707
TI  - The Use of a Combination Antibiogram to Assist with the Selection of Appropriate
      Antimicrobial Therapy for Carbapenemase-Producing Enterobacteriaceae Infections.
AB  - Combination antibiograms can be used to evaluate organism cross-resistance among
      multiple antibiotics. As combination therapy is generally favored for the
      treatment of carbapenemase-producing Enterobacteriaceae (CPE), combination
      antibiograms provide valuable information about the combination of antibiotics
      that achieve the highest likelihood of adequate antibiotic coverage against CPE.

PMID- 26313709
TI  - Enhanced performance of dye-sensitized solar cells aided by Sr,Cr co-doped TiO2
      xerogel films made of uniform spheres.
AB  - One-pot preparation of Sr,Cr co-doped TiO2 xerogel film for boosting the short
      circuit current density of dye-sensitized solar cells (DSCs) is reported. The 2.5
      MUm-diameter spheres are assembled from 60nm nanoparticles by a modified sol-gel
      method. X-ray photoelectron spectroscopy (XPS) shows that Sr(2+) and Cr(3+) ions
      to be well incorporated into the titania crystal lattice without forming specific
      strontium and chromium compositions. The crystallite size, phase composition, and
      band structure of the particles depend on the dopants concentration. Isolated
      energy levels near valence band as a result of the transition ion (i.e., Cr)
      introduction, in conjunction with the local lattice distortions owing to the
      alkaline earth ion (i.e., Sr) insertion, improves the photocatalytic activity of
      the prepared TiO2 spheres, enhancing the short circuit current density of the
      cells. The DSC co-doped with 0.075 at.% Sr and 2.5 at.% Cr (i.e., S7C25 solar
      cell) showed the highest power conversion efficiency of 7.89% and short circuit
      current density of 18.58mA/cm(2) thanks to lower charge transfer resistance
      (2.35Omegacm(2)), lower electron transit time (1.26ms), and higher electron
      diffusion coefficient (17.1*10(4)cm(2)S(-1)) compared to the other cells,
      demonstrated by electrochemical impedance spectroscopy (EIS). The concept of
      simultaneously introduction of alkaline earth ions and transition ions into TiO2
      lattice will open up a new insight into the fabrication of high performance DSCs.

PMID- 26313708
TI  - Mobility among youth in Rakai, Uganda: Trends, characteristics, and associations
      with behavioural risk factors for HIV.
AB  - Mobility, including migration and travel, influences risk of HIV. This study
      examined time trends and characteristics among mobile youth (15-24 years) in
      rural Uganda, and the relationship between mobility and risk factors for HIV. We
      used data from an annual household census and population-based cohort study in
      the Rakai district, Uganda. Data on in-migration and out-migration were collected
      among youth (15-24 years) from 43 communities from 1999 to 2011 (N = 112,117
      observations) and travel among youth residents from 2003 to 2008 (N = 18,318
      observations). Migration and travel were more common among young women than young
      men. One in five youth reported out-migration. Over time, out-migration increased
      among youth and in-migration remained largely stable. Primary reasons for
      migration included work, living with friends or family, and marriage. Recent
      travel within Uganda was common and increased slightly over time in teen women
      (15-19 years old), and young adult men and women (20-24 years old). Mobile youth
      were more likely to report HIV-risk behaviours including: alcohol use, sexual
      experience, multiple partners, and inconsistent condom use. Our findings suggest
      that among rural Ugandan youth, mobility is increasingly common and associated
      with HIV-risk factors. Knowledge of patterns and characteristics of a young, high
      risk mobile population has important implications for HIV interventions.

PMID- 26313710
TI  - Anatase/rutile bi-phasic titanium dioxide nanoparticles for photocatalytic
      applications enhanced by nitrogen doping and platinum nano-islands.
AB  - Titanium dioxide (TiO2) bi-phasic powders with individual particles containing an
      anatase and rutile hetero-junction have been prepared using a sequential layer
      sol-gel deposition technique to soluble substrates. Sequential thin films of
      rutile and subsequently anatase TiO2 were deposited onto sodium chloride
      substrates yielding extremely fragile composite layered discs that fractured into
      "Janus-like" like powders on substrate dissolution. Nitrogen doped and platinum
      sputtered analogues were also prepared, and analysed for photocatalytic potential
      using the photodegradation of Rhodamine B, a model organic pollutant under UV and
      visible light irradiation. The materials were characterised using X-ray
      diffraction, X-ray photoelectron spectroscopy, energy dispersive X-ray
      spectroscopy, Raman spectroscopy and scanning electron microscopy. This paper
      sheds light on the relationship between anatase and rutile materials when in
      direct contact and demonstrates a robust method for the synthesis of bi-phasic
      nanoparticles, ostensibly of any two materials, for photocatalytic reactions or
      otherwise. 

PMID- 26313711
TI  - The impact of particle size on the adsorption of citrate to hematite.
AB  - We investigated the adsorption of citric acid on the surface of two different
      sized hematite nanoparticles using batch adsorption experiments, Fourier
      transform infrared spectroscopy, surface complexation modeling and computational
      molecular modeling. Citrate adsorption reached a maximum between pH approximately
      2.5 and 5.5 and declined as the pH was increased or decreased from that range. At
      high surface loading conditions, the dominant adsorbed citrate structure was
      outer-sphere in nature with a protonation state that varied with pH. At low pH,
      there was also evidence of an inner-sphere complex consistent with a binuclear,
      bidentate structure where the hydroxyl group was deprotonated and played an
      active role in the adsorption. An inner-sphere complex was also detected at low
      citrate surface loading conditions. Surface-area normalized surface coverages
      were similar for both sizes of hematite, however, the inner sphere complex
      appeared to be slightly more prevalent on the smaller hematite. Based on these
      structures, a triple layer surface complexation model comprised of two outer
      sphere complexes and one inner-sphere complex was used to describe the adsorption
      data for both hematite sizes across a range of solution conditions with a single
      set of surface area dependent equilibrium constants. 

PMID- 26313712
TI  - One-pot synthesis of silica-coated copper nanoparticles with high chemical and
      thermal stability.
AB  - With the recent development of nanotechnology, enhancement of the stability of
      nanomaterials is becoming ever more important for their practical applications.
      We studied the silica-coating of Cu nanoparticles and the enhanced stability of
      silica-coated Cu nanoparticles to oxidation. The metallic nanoparticles are
      easily oxidized and agglomerated compared with the bulk metals because the
      nanoparticles possess large specific surfaces. The Cu nanoparticle is one of the
      most difficult nanoparticles to be handled due to its absence of the oxidation
      stability. In the synthesis of silica-coated Cu nanoparticles via a sol-gel
      process using tetraethyl orthosilicate, the addition of NH3 as a catalyst of sol
      gel reaction yielded homogeneous silica-coating. However, a large amount of Cu
      nanoparticles is instantly dissolved by forming complex ions in a NH3 solution
      during and before the silica-coating process. This is the difficulty in the
      silica-coating of Cu nanoparticles. In the present work, the dissolution behavior
      of Cu nanoparticles was electrochemically examined. This electrochemistry-based
      optimization of reducing power of a reaction bath enabled us to synthesize the
      silica-coated Cu nanoparticle via a consecutive liquid-phase reaction which
      requires only basic equipment and involves no separate centrifuging or extraction
      step. Cu nanoparticles coated by silica shells had the remarkable stability even
      in the presence of a strong oxidizing agent. Furthermore, we demonstrated that
      the highly stable Cu nanoparticles can be applied to a red pigment using a unique
      red color of Cu nanoparticles because of its surface plasmon resonance. 

PMID- 26313713
TI  - Metal-organic frameworks-derived synthesis of porous FeP nanocubes: an effective
      peroxidase mimetic.
AB  - Starting with metal-organic frameworks (MOFs), a facile process was demonstrated
      toward the synthesis of porous FeP nanocubes. Herein, Prussian blue nanocubes
      were used as iron-based MOFs precursors, and converted into FeP nanocubes through
      the thermal phosphidation reaction. Then, the FeP nanocubes were exploited as a
      peroxidase mimetic, which not only has the advantages of low cost, high
      stability, and easy preparation, but also follows Michaelis-Menten behaviors and
      shows strong affinity to substrates. On the basis of high catalytic activity of
      FeP nanocubes, a rapid, and convenient approach was developed for the
      colorimetric detection of H2O2 from 2MUM to 130MUM and with a detection limit of
      0.62MUM. The good catalytic activity and high stability make the porous FeP
      nanocubes a useful catalyst for a wide range of potential applications in
      catalysis and biotechnology. 

PMID- 26313714
TI  - Short communication: Flourishing among adolescents with epilepsy: Correlates and
      comparison to peers.
AB  - This study was conducted to examine if adolescents with a seizure
      disorder/epilepsy display less flourishing (thriving) than peers without seizures
      using data from the National Survey of Children's Health 2011-2012. Adolescent
      demographics, symptom severity, and parents' anger toward their child were
      explored as possible predictors of flourishing. Adolescents with seizures
      exhibited lower flourishing than peers, and flourishing among adolescents with
      seizures was predicted by symptom severity, age, race/ethnicity, sex, and
      parental anger. Study results suggest adolescents with a seizure
      disorder/epilepsy should be targeted for interventions that promote flourishing.

PMID- 26313715
TI  - Performance evaluation of maximal separation techniques in immunohistochemical
      scoring of tissue images.
AB  - This paper presents an automatic scoring method for p53 immunostained tissue
      images of oral cancer that consist of tissue image segmentation, splitting of
      clustered nuclei, feature extraction and classification. The tissue images are
      segmented using entropy thresholding technique in which the optimum threshold
      value to each color component is obtained by maximizing the global entropy of its
      gray-level co-occurrence matrix and clustered cells are separated by selectively
      applying marker-controlled watershed transform. Cell nuclei feature is extracted
      by maximal separation technique (MS) based on blue component of tissue image and
      subsequently, each cell is classified into one of four categories using multi
      level thresholding. Finally, IHC score of tissue images have been determined
      using Allred method. A statistical analysis is performed between immuno-score of
      manual and automatic method, and compared with the scores that have obtained
      using other MS techniques. According to the performance evaluation, IHC score
      based on blue component that has high correlation coefficients (CC) of 0.95, low
      mean difference (MD) of 0.15, and a very close range of 95% confidence interval
      with manual scores. Therefore, automatic scoring method presented in this paper
      has high potential to help the pathologist in IHC scoring of tissue images. 

PMID- 26313716
TI  - Nanocrystallization in Oxyfluoride Glasses Controlled by Amorphous Phase
      Separation.
AB  - Transparent bulk glass-ceramics containing ZnF2, K2SiF6, and KZnF3 nanocrystals
      are successfully obtained from xKF-xZnF2-(100 - 2x)SiO2 oxyfluoride glasses for
      the first time to the best of our knowledge. The glass transition temperatures of
      heat-treated samples increase with time and approach values that resemble the
      temperatures chosen for thermal treatment. During nucleation and crystal growth,
      the residual glass around the crystals is depleted in fluoride which as glass
      component usually leads to a decrease in viscosity. The crystallization behavior
      notably depends on the glass composition and changes within a small range from x
      = 20 to 22.5 mol %. The occurrence of liquid/liquid phase separation in
      dependence of the composition is responsible for the physicochemical changes. Two
      different microstructures of droplet and interpenetrating phase separation and
      their compositional evolution are observed by replica transmission electron
      microscopy technique in the multicomponent glassy system. This study suggests
      that the size and crystal phase of precipitated crystallites can be controlled by
      the initial phase separation. 

PMID- 26313717
TI  - Creatine co-ingestion with carbohydrate or cinnamon extract provides no added
      benefit to anaerobic performance.
AB  - The insulin response following carbohydrate ingestion enhances creatine transport
      into muscle. Cinnamon extract is promoted to have insulin-like effects, therefore
      this study examined if creatine co-ingestion with carbohydrates or cinnamon
      extract improved anaerobic capacity, muscular strength, and muscular endurance.
      Active young males (n = 25; 23.7 +/- 2.5 y) were stratified into 3 groups: (1)
      creatine only (CRE); (2) creatine+ 70 g carbohydrate (CHO); or (3) creatine+ 500
      mg cinnamon extract (CIN), based on anaerobic capacity (peak power.kg(-1)) and
      muscular strength at baseline. Three weeks of supplementation consisted of a 5 d
      loading phase (20 g/d) and a 16 d maintenance phase (5 g/d). Pre- and post
      supplementation measures included a 30-s Wingate and a 30-s maximal running test
      (on a self-propelled treadmill) for anaerobic capacity. Muscular strength was
      measured as the one-repetition maximum 1-RM for chest, back, quadriceps,
      hamstrings, and leg press. Additional sets of the number of repetitions performed
      at 60% 1-RM until fatigue measured muscular endurance. All three groups
      significantly improved Wingate relative peak power (CRE: 15.4% P = .004; CHO:
      14.6% P = .004; CIN: 15.7%, P = .003), and muscular strength for chest (CRE: 6.6%
      P < .001; CHO: 6.7% P < .001; CIN: 6.4% P < .001), back (CRE: 5.8% P < .001; CHO:
      6.4% P < .001; CIN: 8.1% P < .001), and leg press (CRE: 11.7% P = .013; CHO:
      10.0% P = .007; CIN: 17.3% P < .001). Only the CRE (10.4%, P = .021) and CIN
      (15.5%, P < .001) group improved total muscular endurance. No differences existed
      between groups post-supplementation. These findings demonstrate that three
      different methods of creatine ingestion lead to similar changes in anaerobic
      power, strength, and endurance. 

PMID- 26313718
TI  - D-Isonucleotide (isoNA) incorporation around cleavage site of passenger strand
      promotes the vibration of Ago2-PAZ domain and enhances in vitro potency of siRNA.
AB  - It has been demonstrated that passenger strand cleavage is important for the
      activation of RNA-induced silencing complex (RISC), which is a crucial step for
      siRNA-mediated gene silencing. Herein, we report that isonucleotide (isoNA)
      modification around the cleavage site of the passenger strand would affect the in
      vitro potency of modified siRNAs by altering the motion pattern of the Ago2-PAZ
      domain. According to western blotting, q-PCR and antiviral test results, we
      proved that D-isonucleotide (isoNA) modification at the position 8 of the
      passenger strand (siMek1-S08D), which is adjacent to the cleavage site, markedly
      improved the in vitro potency of the modified siRNA, whereas siRNAs with D-isoNA
      incorporation at position 9 (siMek1-S09D) or L-isoNA incorporation at positions 8
      and 9 (siMek1-S08L, siMek1-S09L) displayed lower activity compared to native
      siRNA. Kinetics evaluation of passenger strand cleavage induced by T.
      thermophilus Ago (Tt-Ago) showed that D-isoNA modification at position 8 of the
      passenger strand had no significant influence on the cleavage rate, but L-isoNA
      modification at position 8 slowed the cleavage rate markedly. Moreover, the
      results of molecular dynamics simulations showed that D-isoNA modification at
      position 8 affected the open-close motion of the PAZ domain in the Ago/siRNA
      complex, which may promote the loading of RISC and release of a passenger strand
      cleavage product, and consequently accelerate the activation of RISC and enhance
      silencing activity. However, D-isoNA modification at position 9 or L-isoNA
      modification at position 8 or 9 exerted opposite influences on the motion of the
      Ago-PAZ domain.

PMID- 26313719
TI  - Hydrocortisone supresses inflammatory activity of metalloproteinase-8 in carotid
      plaque.
AB  - OBJECTIVE: Matrix metalloproteinases are inflammatory biomarkers involved in
      carotid plaque instability. Our objective was to analyze the inflammatory
      activity of plasma and carotid plaque MMP-8 and MMP-9 after intravenous
      administration of hydrocortisone. METHODS: The study included 22 patients with
      stenosis >= 70% in the carotid artery (11 symptomatic and 11 asymptomatic) who
      underwent carotid endarterectomy. The patients were divided into two groups:
      Control Group - hydrocortisone was not administered, and Group 1 - 500 mg
      intravenous hydrocortisone was administered during anesthetic induction. Plasma
      levels of MMP-8 and MMP-9 were measured preoperatively (24 hours before carotid
      endarterectomy) and at 1 hour, 6 hours and 24 hours after carotid endarterectomy.
      In carotid plaque, tissue levels of MMP-8 and MMP-9 were measured. RESULTS: Group
      1 showed increased serum levels of MMP- 8 (994.28 pg/ml and 408.54 pg/ml,
      respectively; P=0.045) and MMP-9 (106,656.34 and 42,807.69 respectively; P=0.014)
      at 1 hour after carotid endarterectomy compared to the control group. Symptomatic
      patients in Group 1 exhibited lower tissue concentration of MMP-8 in comparison
      to the control group (143.89 pg/ml and 1317.36 respectively; P=0.003). There was
      a correlation between preoperative MMP-9 levels and tissue concentrations of MMP
      8 (P=0.042) and MMP-9 (P=0.019) between symptomatic patients in the control
      group. CONCLUSION: Hydrocortisone reduces the concentration of MMP- 8 in carotid
      plaque, especially in symptomatic patients. There was an association between
      systemic and tissue inflammation.

PMID- 26313720
TI  - Factors associated with moderate or severe left atrioventricular valve
      regurgitation within 30 days of repair of complete atrioventricular septal
      defect.
AB  - INTRODUCTION: Left atrioventricular valve regurgitation is the most concerning
      residual lesion after surgical correction of atrioventricular septal defects.
      OBJECTIVE: To determine factors associated with moderate or severe left
      atrioventricular valve regurgitation within 30 days of surgical repair of
      complete atrioventricular septal defect. METHODS: We assessed the results of 53
      consecutive patients 3 years-old and younger presenting with complete
      atrioventricular septal defect that were operated on at our practice between 2002
      and 2010. The following variables were considered: age, weight, absence of Down
      syndrome, grade of preoperative atrioventricular valve regurgitation,
      abnormalities on the left atrioventricular valve and the use of annuloplasty.
      Median age was 6.7 months; median weight was 5.3 Kg; 86.8% had Down syndrome. At
      the time of preoperative evaluation, there were 26 cases with moderate or severe
      left atrioventricular valve regurgitation (49.1%). Abnormalities on the left
      atrioventricular valve were found in 11.3%; annuloplasty was performed in 34% of
      the patients. RESULTS: At the time of postoperative evaluation, there were 21
      cases with moderate or severe left atrioventricular valve regurgitation (39.6%).
      After performing a multivariate analysis, the only significant factor associated
      with moderate or severe left atrioventricular valve regurgitation was the absence
      of Down syndrome (P=0.03). CONCLUSION: Absence of Down syndrome was associated
      with moderate or severe postoperative left atrioventricular valve regurgitation
      after surgical repair of complete atrioventricular septal defect at our practice.

PMID- 26313722
TI  - Incidence of postoperative atrial fibrillation in patients undergoing on-pump and
      off-pump coronary artery bypass grafting.
AB  - OBJECTIVE: To determine the incidence of postoperative atrial fibrillation in
      patients undergoing on-pump and off-pump coronary artery bypass grafting.
      METHODS: A retrospective study with analysis of 230 medical records between
      January 2011 and October 2013 was conducted. RESULTS: Fifty-six (24.3%) out of
      the 230 patients were female. The average age of patients undergoing on-pump
      coronary artery bypass grafting was 59.91+/-8.62 years old, and off-pump was
      57.16+/-9.01 years old (P=0.0213). The average EuroSCORE for the on-pump group
      was 3.37%+/-3.08% and for the off-pump group was 3.13%+/-3% (P=0.5468). Eighteen
      (13.43%) patients who underwent off-pump coronary artery bypass grafting
      developed postoperative atrial fibrillation, whereas for the onpump group, 19
      (19.79%) developed this arrhythmia, with no significant difference between the
      groups (P=0.1955). CONCLUSION: Off-pump coronary artery bypass grafting did not
      reduce the incidence of atrial fibrillation in the postoperative period.
      Important predictors of risk for the development of this arrhythmia were
      identified as: patients older than 70 years old and presence of atrial
      fibrillation in perioperative period in both groups, and non-use of beta-blockers
      drugs postoperatively in the on-pump group.

PMID- 26313721
TI  - Chronotropic incompetence in Chagas disease: effectiveness of blended sensor
      (volume/minute and accelerometer).
AB  - INTRODUCTION: Technological progress of pacemakers has allowed the association of
      two or more sensors in one heart rate system response. The accelerometer sensor
      measures the intensity of the activity; it has a relatively rapid response to the
      beginning of it, however, it may present insufficient response to less strenuous
      or of less impact exercise. The minute ventilation sensor changes the pacing rate
      in response to changes in respiratory frequency in relation to tidal volume,
      allowing responses to situations of emotional stress and low impact exercises.
      OBJECTIVE: To evaluate the cardiorespiratory response of the accelerometer with
      respect to the blended sensor (BS=accelerometer sensor+minute ventilation sensor)
      to exercise in chagasic patients undergoing cardiopulmonary exercise test.
      METHODS: This was a prospective, observational, randomized, cross-sectional
      study. Patients who met the inclusion criteria were selected. The maximum heart
      rate of the sensor was programmed by age (220-age). The results were analyzed
      through t test with paired samples (P<0.05). RESULTS: Sample was comprised of 44
      patients, with a mean age of 66+/-10.4 years, 58% were female, 54% as first
      implant, in 74% were functional class I and 26% were functional class II, left
      ventricular ejection fraction was 58+/-7. As for the cardiopulmonary test,
      maximum expected heart rate and VO2 were not achieved in both the accelerometer
      sensor and the blended sensor, however, metabolic equivalent in the blended
      sensor was higher than the expected, all data with P<0.001. CONCLUSION: Even
      though the maximal heart rate was not reached, the blended sensor provided a
      physiological electrical sequence when compared to the accelerometer sensor,
      providing better physical fitness test in cardiopulmonary hemodynamics and
      greater efficiency.

PMID- 26313723
TI  - Mitral annulus morphologic and functional analysis using real time tridimensional
      echocardiography in patients submitted to unsupported mitral valve repair.
AB  - INTRODUCTION: Mitral valve repair is the treatment of choice to correct mitral
      insufficiency, although the literature related to mitral valve annulus behavior
      after mitral repair without use of prosthetic rings is scarce. OBJECTIVE: To
      analyze mitral annulus morphology and function using real time tridimensional
      echocardiography in individuals submitted to mitral valve repair with Double
      Teflon technique. METHODS: Fourteen patients with mitral valve insufficiency
      secondary to mixomatous degeneration that were submitted to mitral valve repair
      with the Double Teflon technique were included. Thirteen patients were in FC
      III/IV. Patients were evaluated in preoperative period, immediate postoperative
      period, 6 months and 1 year after mitral repair. Statistical analysis was made by
      repeated measures ANOVA test and was considered statistically significant P<0.05.
      RESULTS: There were no deaths, reoperation due to valve dysfunction,
      thromboembolism or endocarditis during the study. Posterior mitral annulus
      demonstrated a significant reduction in immediate postoperative period (P<0.001),
      remaining stable during the study, and presents a mean of reduction of 25.8%
      comparing with preoperative period. There was a significant reduction in
      anteroposterior and mediolateral diameters in the immediate postoperative period
      (P<0.001), although there was a significant increase in mediolateral diameter
      between immediate postoperative period and 1 year. There was no difference in
      mitral internal area variation over the cardiac cycle during the study.
      CONCLUSION: Segmentar annuloplasty reduced the posterior component of mitral
      annulus, which remained stable in a 1-year-period. The variation in mitral
      annulus area during cardiac cycle remained stable during the study.

PMID- 26313724
TI  - Impact of body mass index on outcome in patients undergoing coronary artery
      bypass grafting and/or valve replacement surgery.
AB  - OBJECTIVE: This study aimed to analyze the impact of body mass index on outcomes
      of 101 patients undergoing coronary artery bypass grafting, valve replacement, or
      combined valve/ coronary artery bypass grafting surgery in a private hospital in
      Belo Horizonte, Brazil. METHODS: This was a prospective cross-sectional study of
      patients undergoing cardiac surgery from May 2009 to December 2012. All patients
      were followed up from the first day of admission until discharge or death.
      Patients were divided into three groups according to BMI: normal weight,
      overweight, and obese. The main outcome measure was the association between BMI
      and postoperative morbidities and mortality. RESULTS: Multivariate analysis
      identified obesity as an independent predictor of increased risk of surgical
      reintervention (odds ratio [OR] 13.6; 95%CI 1.1 - 162.9; P=0.046) and reduced
      risk of bleeding (OR 0.05; 95% CI 0.09 - 0.69; P=0.025). Univariate analysis
      showed that obesity was associated with increased frequency of wound dehiscence
      (P=0.021). There was no association between BMI and other complications or
      mortality in univariate analysis. There was also no association between body mass
      index and duration of cardiopulmonary bypass, aortic clamping, mechanical
      ventilation, and intensive care unit or hospital stay. CONCLUSION: Obese
      individuals undergoing coronary artery bypass grafting, valve replacement, or
      combined surgery have a higher postoperative risk of surgical reintervention and
      lower chances of bleeding.

PMID- 26313725
TI  - Surgery of the aortic root: should we go for the valve-sparing root
      reconstruction or the composite graft-valve replacement is still the first choice
      of treatment for these patients?
AB  - OBJECTIVE: To compare the results of the root reconstruction with the aortic
      valve-sparing operation versus composite graft-valve replacement. METHODS: From
      January 2002 to October 2013, 324 patients underwent aortic root reconstruction.
      They were 263 composite graft-valve replacement and 61 aortic valve-sparing
      operation (43 reimplantation and 18 remodeling). Twenty-six percent of the
      patients were NYHA functional class III and IV; 9.6% had Marfan syndrome, and 12%
      had bicuspid aortic valve. There was a predominance of aneurysms over dissections
      (81% vs. 19%), with 7% being acute dissections. The complete follow-up of 100% of
      the patients was performed with median follow-up time of 902 days for patients
      undergoing composite graft-valve replacement and 1492 for those undergoing aortic
      valve-sparing operation. RESULTS: In-hospital mortality was 6.7% and 4.9%,
      respectively for composite graft-valve replacement and aortic valve-sparing
      operation (ns). During the late follow-up period, there was 0% moderate and 15.4%
      severe aortic regurgitation, and NYHA functional class I and II were 89.4% and
      94%, respectively for composite graft-valve replacement and aortic valve-sparing
      operation (ns). Root reconstruction with aortic valve-sparing operation showed
      lower late mortality (P=0.001) and lower bleeding complications (P=0.006). There
      was no difference for thromboembolism, endocarditis, and need of reoperation.
      CONCLUSION: The aortic root reconstruction with preservation of the valve should
      be the operation being performed for presenting lower late mortality and survival
      free of bleeding events.

PMID- 26313726
TI  - Effect of remote ischemic postconditioning in inflammatory changes of the lung
      parenchyma of rats submitted to ischemia and reperfusion.
AB  - OBJECTIVE: To assess the effects of postconditioning remote in ischemia
      reperfusion injury in rat lungs. METHODS: Wistar rats (n=24) divided into 3
      groups: GA (I/R) n=8, GB (R-Po) n=8, CG (control) n=8, underwent ischemia for 30
      minutes artery occlusion abdominal aorta, followed by reperfusion for 60 minutes.
      Resected lungs and performed histological analysis and classification of
      morphological findings in accordance with the degree of tissue injury.
      Statistical analysis of the mean rating of the degree of tissue injury. RESULTS:
      GA (3.6), GB (1.3) and CG (1.0). (GA GB X P<0.05). CONCLUSION: The remote
      postconditioning was able to minimize the inflammatory lesion of the lung
      parenchyma of rats undergoing ischemia and reperfusion process.

PMID- 26313727
TI  - Impact of respiratory infection in the results of cardiac surgery in a tertiary
      hospital in Brazil.
AB  - OBJECTIVE: To assess the impact of respiratory tract infection in the
      postoperative period of cardiac surgery in relation to mortality and to identify
      patients at higher risk of developing this complication. METHODS: Cross-sectional
      observational study conducted at the Recovery of Cardiothoracic Surgery, using
      information from a database consisting of a total of 900 patients operated on in
      this hospital during the period from 01/07/2008 to 1/07/2009. We included
      patients whose medical records contained all the information required and
      undergoing elective surgery, totaling 109 patients with two excluded. Patients
      were divided into two groups, WITH and WITHOUT respiratory tract infection, as
      the development or respiratory tract infection in hospital, with patients in the
      group without respiratory tract infection, the result of randomization, using for
      the pairing of the groups the type of surgery performed. The outcome variables
      assessed were mortality, length of hospital stay and length of stay in intensive
      care unit. The means of quantitative variables were compared using the Wilcoxon
      and student t-test. RESULTS: The groups were similar (average age P=0.17; sex
      P=0.94; surgery performed P=0.85-1.00) Mortality in the WITH respiratory tract
      infection group was significantly higher (P<0.0001). The times of hospitalization
      and intensive care unit were significantly higher in respiratory tract infection
      (P<0.0001). The presence of respiratory tract infection was associated with the
      development of other complications such as renal failure dialysis and stroke
      P<0.00001 and P=0.002 respectively. CONCLUSION: The development of respiratory
      tract infection postoperative cardiac surgery is related to higher mortality,
      longer periods of hospitalization and intensive care unit stay.

PMID- 26313728
TI  - Risk factors for perioperative ischemic stroke in cardiac surgery.
AB  - OBJECTIVE: The purpose of this study was to evaluate the risk factors for
      ischemic stroke in patients undergoing cardiac surgery. METHODS: From January
      2010 to December 2012, 519 consecutive patients undergoing cardiac surgery were
      analyzed prospectively. The sample was divided into two groups: patients with
      stroke per and postoperative were allocated in Group GS (n=22) and the other
      patients in the group CCONTROL (n=497). The following variables were compared
      between the groups: gender, age, carotid stenosis > 70%, diabetes on insulin,
      chronic obstructive pulmonary disease, peripheral arteriopathy, unstable angina,
      kidney function, left ventricular function, acute myocardial infarction,
      pulmonary arterial hypertension, use of cardiopulmonary bypass. Ischemic stroke
      was defined as symptoms lasting over 24 hours associated with changes in brain
      computed tomography scan. The variables were compared using Fisher's exact test,
      Chi square, Student's t-test and logistic regression. RESULTS: Stroke occurred in
      4.2% of patients and the risk factors statistically significant were: carotid
      stenosis of 70% or more (P=0.03; OR 5.07; IC 95%: 1.35 to 19.02), diabetes on
      insulin (P=0.04; OR 2.61; IC 95%: 1.10 to 6.21) and peripheral arteriopathy
      (P=0.03; OR 2.61; 95% CI: 1.08 to 6.28). CONCLUSION: Risk factors for ischemic
      stroke were carotid stenosis of 70% or more, diabetes on insulin and peripheral
      arteriopathy.

PMID- 26313729
TI  - Recommendations for starting a grown up congenital heart disease (GUCH) unit.
AB  - During the last decades, advances in diagnosis and treatment of congenital heart
      disease have allowed many individuals to reach adulthood. Due mainly to the great
      diagnostic diversity and to the co-morbidities usually present in this age group,
      these patients demand assistance in a multidisciplinary facility if an adequate
      attention is aimed. In this paper we reviewed, based in the international
      literature and also on the authors' experience, the structural conditions that
      should be available for these patients. We highlighted aspects like the facility
      characteristics, the criteria usually adopted for patient transfer from the
      paediatric setting, the composition of the medical and para- medical staff taking
      into account the specific problems, and also the model of outpatient and in
      hospital assistance. We also emphasized the importance of patient data storage,
      the fundamental necessity of institutional support and also the compromise to
      offer professional training. The crucial relevance of clinical research is also
      approached, particularly the development of multicenter studies as an appropriate
      methodology for this heterogeneous patient population. 

PMID- 26313730
TI  - MicroRNAs and mesenchymal stem cells: hope for pulmonary hypertension.
AB  - Pulmonary hypertension is a devastating and refractory disease and there is no
      cure for this disease. Recently, microRNAs and mesenchymal stem cells emerged as
      novel methods to treat pulmonary hypertension. More than 20 kinds of microRNAs
      may participate in the process of pulmonary hypertension. It seems microRNAs or
      mesenchymal stem cells can ameliorate some symptoms of pulmonary hypertension in
      animals and even improve heart and lung function during pulmonary hypertension.
      Nevertheless, the relationship between mesenchymal stem cells, microRNAs and
      pulmonary hypertension is not clear. And the mechanisms underlying their function
      still need to be investigated. In this study we review the recent findings in
      mesenchymal stem cells - and microRNAs-based pulmonary hypertension treatment,
      focusing on the potential role of microRNAs regulated mesenchymal stem cells in
      pulmonary hypertension and the role of exosomes between mesenchymal stem cells
      and pulmonary hypertension. 

PMID- 26313731
TI  - Cardiac myxoma in pregnancy: a comprehensive review.
AB  - OBJECTIVE: Cardiac myxoma in pregnancy is rare and the clinical characteristics
      of this entity have been insufficiently elucidated. This article aims to describe
      the treatment options and the risk factors responsible for the maternal and feto
      neonatal prognoses. METHODS: A comprehensive search of the literature of cardiac
      myxoma in pregnancy was conducted and 44 articles with 51 patients were included
      in the present review. RESULTS: Transthoracic echocardiography was the most
      common diagnostic tool for the diagnosis of cardiac myxoma during pregnancy.
      Cardiac myxoma resection was performed in 95.9% (47/49); while no surgical
      resection was performed in 4.1% (2/49) patients (P=0.000). More patients had an
      isolated cardiac myxoma resection in comparison to those with a concurrent or
      staged additional cardiac operation [87.2% (41/47) vs. 12.8% (6/47), P=0.000]. A
      voluntary termination of the pregnancy was done in 7 (13.7%) cases. In the
      remaining 31 (60.8%) pregnant patients, cesarean section was the most common
      delivery mode representing 61.3% and vaginal delivery was more common accounting
      for 19.4%. Cardiac surgery was performed in the first, second and third trimester
      in 5 (13.9%), 14 (38.9%) and 17 (47.2%) patients, respectively. No patients died.
      In the delivery group, 20 (76.9%) neonates were event-free survivals, 4 (15.4%)
      were complicated and 2 (7.7%) died. Neonatal prognoses did not differ between the
      delivery modes, treatment options, timing of cardiac surgery and sequence of
      cardiac myxoma resection in relation to delivery. CONCLUSION: The diagnosis of
      cardiac myxoma in pregnancy is important. Surgical treatment of cardiac myxoma in
      the pregnant patients has brought about favorable maternal and feto-neonatal
      outcomes in the delivery group, which might be attributable to the shorter
      operation duration and non-emergency nature of the surgical intervention. Proper
      timing of cardiac surgery and improved cardiopulmonary bypass conditions may
      result in even better maternal and feto-neonatal survivals.

PMID- 26313732
TI  - Heart lessons.

PMID- 26313733
TI  - Chronotropic incompetence in Chagas disease: usefulness of dual sensor pacemaker
      based on volume minute and accelerometer.

PMID- 26313734
TI  - Grown up congenital hearts.

PMID- 26313735
TI  - A new perspective: imaging the stereochemistry of molecular collisions.
AB  - The concept of the steric effect in molecular collisions is central to chemistry.
      In this Perspective article we review some of the progress made in studying the
      steric effect in inelastic and reactive collisions involving relatively small
      isolated atomic and molecular species. We overview the theoretical framework used
      to quantify the steric effect, and outline some of the key experimental
      approaches that can be employed to study the dynamics and mechanism of collisions
      involving oriented and aligned molecules. We illustrate the discussion by
      highlighting a few recent studies of inelastic and reactive scattering. Finally,
      we conclude with some reflections on possible future directions of interest. 

PMID- 26313736
TI  - Increased soil phosphorus availability induced by faba bean root exudation
      stimulates root growth and phosphorus uptake in neighbouring maize.
AB  - Root growth is influenced by soil nutrients and neighbouring plants, but how
      these two drivers affect root interactions and regulate plant growth dynamics is
      poorly understood. Here, interactions between the roots of maize (Zea mays) and
      faba bean (Vicia faba) are characterized. Maize was grown alone (maize) or with
      maize (maize/maize) or faba bean (maize/faba bean) as competitors under five
      levels of phosphorus (P) supply, and with homogeneous or heterogeneous P
      distribution. Maize had longer root length and greater shoot biomass and P
      content when grown with faba bean than with maize. At each P supply rate, faba
      bean had a smaller root system than maize but greater exudation of citrate and
      acid phosphatase, suggesting a greater capacity to mobilize P in the rhizosphere.
      Heterogeneous P availability enhanced the root-length density of maize but not
      faba bean. Maize root proliferation in the P-rich patches was associated with
      increased shoot P uptake. Increased P availability by localized P application or
      by the presence of faba bean exudation stimulated root morphological plasticity
      and increased shoot growth in maize in the maize/faba bean mixture, suggesting
      that root interactions of neighbouring plants can be modified by increased P
      availability. 

PMID- 26313738
TI  - Nucleation and growth of a helical nanofilament (B4) liquid-crystal phase
      confined in nanobowls.
AB  - The B4 helical nanofilament (HNF) liquid crystal (LC) phase is a three
      dimensional (3D) helical structure composed of 2D smectic layers. Because of the
      complex shape of the HNF phase, it is difficult to understand the generation
      mechanism of HNFs in the bulk as well as in the thin-film condition. Here, we
      directly investigated the nucleation and growth of HNFs in nanobowls. A
      combination of electron microscopy and X-ray diffraction was used to reveal the
      transitional surface structures, in which barrel-like structures as well as short
      HNFs with random handedness were observed, depending on the LC film thickness.
      These results will be useful in achieving a better understanding of thin film
      structures of complex chiral structures in soft matter. 

PMID- 26313737
TI  - Ultrashort-TE stimulated echo acquisition mode (STEAM) improves the
      quantification of lipids and fatty acid chain unsaturation in the human liver at
      7 T.
AB  - Ultrahigh-field, whole-body MR systems increase the signal-to-noise ratio (SNR)
      and improve the spectral resolution. Sequences with a short TE allow fast signal
      acquisition with low signal loss as a result of spin-spin relaxation. This is of
      particular importance in the liver for the precise quantification of the
      hepatocellular content of lipids (HCL). In this study, we introduce a spoiler
      Gradient-switching Ultrashort STimulated Echo AcqUisition (GUSTEAU) sequence,
      which is a modified version of a stimulated echo acquisition mode (STEAM)
      sequence, with a minimum TE of 6 ms. With the high spectral resolution at 7 T,
      the efficient elimination of water sidebands and the post-processing suppression
      of the water signal, we estimated the composition of fatty acids (FAs) via the
      detection of the olefinic lipid resonance and calculated the unsaturation index
      (UI) of hepatic FAs. The performance of the GUSTEAU sequence for the assessment
      of UI was validated against oil samples and provided excellent results in
      agreement with the data reported in the literature. When measuring HCL with
      GUSTEAU in 10 healthy volunteers, there was a high correlation between the
      results obtained at 7 and 3 T (R(2) = 0.961). The test-retest measurements
      yielded low coefficients of variation for HCL (4 +/- 3%) and UI (11 +/- 8%) when
      measured with the GUSTEAU sequence at 7 T. A negative correlation was found
      between UI and HCL (n = 10; p < 0.033). The ultrashort TE MRS sequence (GUSTEAU;
      TE = 6 ms) provided high repeatability for the assessment of HCL. The improved
      spectral resolution at 7 T with the elimination of water sidebands and the
      offline water subtraction also enabled an assessment of the unsaturation of FAs.
      This all highlights the potential use of this MRS acquisition scheme for studies
      of hepatic lipid composition in vivo.

PMID- 26313739
TI  - Thermal transport in MoS2/Graphene hybrid nanosheets.
AB  - Heat dissipation is a very critical problem for designing nano-functional
      devices, including MoS2/graphene heterojunctions. In this paper we investigate
      thermal transport in MoS2/graphene hybrid nanosheets under various heating
      conditions, by using molecular dynamics simulation. Diverse transport processes
      and characteristics, depending on the conducting layers, are found in these
      structures. The thermal conductivities can be tuned by interlayer coupling,
      environment temperature, and interlayer overlap. The highest thermal conductivity
      at room temperature is achieved as more than 5 times of that of single-layer MoS2
      when both layers are heated and 100% overlapped. Different transport mechanisms
      in the hybrid nanosheets are explained by phonon density of states, temperature
      distribution, and interlayer thermal resistance. Our results could not only
      provide clues to master the heat transport in functional devices based on
      MoS2/graphene heterojunctions, but are also useful for analyzing thermal
      transport in other van der Waals hybrid nanosheets. 

PMID- 26313740
TI  - Asynchronous onset of eutrophication among shallow prairie lakes of the Northern
      Great Plains, Alberta, Canada.
AB  - Coherent timing of agricultural expansion, fertilizer application, atmospheric
      nutrient deposition, and accelerated global warming is expected to promote
      synchronous fertilization of regional surface waters and coherent development of
      algal blooms and lake eutrophication. While broad-scale cyanobacterial expansion
      is evident in global meta-analyses, little is known of whether lakes in discrete
      catchments within a common lake district also exhibit coherent water quality
      degradation through anthropogenic forcing. Consequently, the primary goal of this
      study was to determine whether agricultural development since ca. 1900,
      accelerated use of fertilizer since 1960, atmospheric deposition of reactive N,
      or regional climate warming has resulted in coherent patterns of eutrophication
      of surface waters in southern Alberta, Canada. Unexpectedly, analysis of
      sedimentary pigments as an index of changes in total algal abundance since ca.
      1850 revealed that while total algal abundance (as beta-carotene, pheophytin a)
      increased in nine of 10 lakes over 150 years, the onset of eutrophication varied
      by a century and was asynchronous across basins. Similarly, analysis of temporal
      sequences with least-squares regression revealed that the relative abundance of
      cyanobacteria (echinenone) either decreased or did not change significantly in
      eight of the lakes since ca. 1850, whereas purple sulfur bacteria (as okenone)
      increased significantly in seven study sites. These patterns are consistent with
      the catchment filter hypothesis, which posits that lakes exhibit unique responses
      to common forcing associated with the influx of mass as water, nutrients, or
      particles.

PMID- 26313741
TI  - Harnessing Intracellular Biochemical Pathways for In Vitro Synthesis of Designer
      Tellurium Nanorods.
AB  - Synthesizing nanomaterials of desired properties is a big challenge, which
      requires extremely harsh conditions and/or use of toxic materials. More recently
      developed in vivo methods have brought a different set of problems such as
      separation and purification of nanomaterials made in vivo. Here, a novel approach
      that harnesses cellular pathways for in vitro synthesis of high-quality tellurium
      nanorods with tunable lengths and optical properties is reported. It is first
      demonstrated that in vivo biochemical pathways could be used to synthesize Te
      nanorods via the intracellular reduction of TeO3(2-) in living Staphylococcus
      aureus cells. The pathways to set up a quasi-biological system for Te precursor
      formation are then utilized, which could further synthesize Te nanorods in vitro.
      This allows to successfully synthesize in vitro, under routine laboratory
      conditions, Te nanorods with uniform and tunable lengths, ranging from about 10
      to 200 nm, and controllable optical properties with high molar extinction
      coefficients. The approach here should open new avenues for controllable, facile,
      and efficient synthesis of designer nanomaterials for diverse industrial and
      biomedical applications.

PMID- 26313742
TI  - Cooperative Photo-/Lewis Acid Catalyzed Tandem Intramolecular [3 + 2] Cross
      Cycloadditions of Cyclopropane 1,1-Diesters with alpha,beta-Unsaturated Carbonyls
      for Medium-Sized Carbocycles.
AB  - A tandem isomerization/intramolecular [3 + 2] cross-cycloaddition (IMCC) of
      cyclopropane 1,1-diesters with alpha,beta-unsaturated ketones/aldehydes under a
      cooperative catalysis of photo and Lewis acids has been successfully developed.
      This supplied a general and efficient strategy for construction of medium-sized
      carbocyclic (8-, 9-, and 10-membered) skeletons as well as such carbocycle-based
      bridged oxa-bicyclo[n.2.1] (n = 4-6) skeletons. 

PMID- 26313743
TI  - Uptake of Gold Nanoparticles by Intestinal Epithelial Cells: Impact of Particle
      Size on Their Absorption, Accumulation, and Toxicity.
AB  - Inorganic nanomaterials have been increasingly utilized in many consumer
      products, which has led to concerns about their potential toxicity. At present,
      there is limited knowledge about the gastrointestinal fate and cytotoxicity of
      ingested inorganic nanoparticles. This study determined the influence of particle
      size and concentration of gold nanoparticles (AuNPs) on their absorption,
      accumulation, and cytotoxicity in model intestinal epithelial cells. As the mean
      particle diameter of the AuNPs decreased (from 100 to 50 to 15 nm), their rate of
      absorption by the intestinal epithelium cells increased, but their cellular
      accumulation in the epithelial cells decreased. Moreover, accumulation of AuNPs
      caused cytotoxicity in the intestinal epithelial cells, which was evidenced by
      depolarization of mitochondria membranes. These results provide important
      insights into the relationship between the dimensions of AuNPs and their
      gastrointestinal uptake and potential cytotoxicity. 

PMID- 26313744
TI  - An Efficient Genotyping Method in Chicken Based on Genome Reducing and
      Sequencing.
AB  - Single nucleotide polymorphisms (SNPs) are essential for identifying the genetic
      mechanisms of complex traits. In the present study, we applied genotyping by
      genome reducing and sequencing (GGRS) method to construct a 252-plex sequencing
      library for SNP discovery and genotyping in chicken. The library was successfully
      sequenced on an Illumina HiSeq 2500 sequencer with a paired-end pattern;
      approximately 400 million raw reads were generated, and an average of
      approximately 1.4 million good reads per sample were generated. A total of 91,767
      SNPs were identified after strict filtering, and all of the 252 samples and all
      of the chromosomes were well represented. Compared with the Illumina 60K chicken
      SNP chip data, approximately 34,131 more SNPs were identified using GGRS, and a
      higher SNP density was found using GGRS, which could be beneficial for downstream
      analysis. Using the GGRS method, more than 3528 samples can be sequenced
      simultaneously, and the cost is reduced to $18 per sample. To the best of our
      knowledge, this study describes the first report of such highly multiplexed
      sequencing in chicken, indicating potential applications for genome-wide
      association and genomic selection in chicken. 

PMID- 26313745
TI  - Drosophila Hrp48 Is Required for Mushroom Body Axon Growth, Branching and
      Guidance.
AB  - RNA binding proteins assemble on mRNAs to control every single step of their life
      cycle, from nuclear splicing to cytoplasmic localization, stabilization or
      translation. Consistent with an essential role of RNA binding proteins in
      neuronal maturation and function, mutations in this class of proteins, in
      particular in members of the hnRNP family, have been associated with neurological
      diseases. To date, however, the physiological function of hnRNPs during in vivo
      neuronal development has remained poorly explored. Here, we have investigated the
      role of Drosophila Hrp48, a fly homologue of mammalian hnRNP A2/B1, during
      central nervous system development. Using a combination of mutant conditions, we
      showed that hrp48 is required for the formation, growth and guidance of axonal
      branches in Mushroom Body neurons. Furthermore, our results revealed that hrp48
      inactivation induces an overextension of Mushroom Body dorsal axonal branches,
      with a significantly higher penetrance in females than in males. Finally, as
      demonstrated by immunolocalization studies, Hrp48 is confined to Mushroom Body
      neuron cell bodies, where it accumulates in the cytoplasm from larval stages to
      adulthood. Altogether, our data provide evidence for a crucial in vivo role of
      the hnRNP Hrp48 in multiple aspects of axon guidance and branching during nervous
      system development. They also indicate cryptic sex differences in the development
      of sexually non-dimorphic neuronal structures. 

PMID- 26313747
TI  - Autophagic death probed by photodynamic therapy.
AB  - The high degree of selectivity for photodamage to subcellular organelles can
      provide a means for evaluation of autophagic death pathways. While many current
      reports rely on ambiguous criteria, there are glimmers of unequivocal evidence. 

PMID- 26313746
TI  - Extracellular Adenosine Protects against Streptococcus pneumoniae Lung Infection
      by Regulating Pulmonary Neutrophil Recruitment.
AB  - An important determinant of disease following Streptococcus pneumoniae
      (pneumococcus) lung infection is pulmonary inflammation mediated by
      polymorphonuclear leukocytes (PMNs). We found that upon intratracheal challenge
      of mice, recruitment of PMNs into the lungs within the first 3 hours coincided
      with decreased pulmonary pneumococci, whereas large numbers of pulmonary PMNs
      beyond 12 hours correlated with a greater bacterial burden. Indeed, mice that
      survived infection largely resolved inflammation by 72 hours, and PMN depletion
      at peak infiltration, i.e. 18 hours post-infection, lowered bacterial numbers and
      enhanced survival. We investigated host signaling pathways that influence both
      pneumococcus clearance and pulmonary inflammation. Pharmacologic inhibition
      and/or genetic ablation of enzymes that generate extracellular adenosine (EAD)
      (e.g. the ectoenzyme CD73) or degrade EAD (e.g. adenosine deaminase) revealed
      that EAD dramatically increases murine resistance to S. pneumoniae lung
      infection. Moreover, adenosine diminished PMN movement across endothelial
      monolayers in vitro, and although inhibition or deficiency of CD73 had no
      discernible impact on PMN recruitment within the first 6 hours after
      intratracheal inoculation of mice, these measures enhanced PMN numbers in the
      pulmonary interstitium after 18 hours of infection, culminating in dramatically
      elevated numbers of pulmonary PMNs at three days post-infection. When assessed at
      this time point, CD73-/- mice displayed increased levels of cellular factors that
      promote leukocyte migration, such as CXCL2 chemokine in the murine lung, as well
      as CXCR2 and beta-2 integrin on the surface of pulmonary PMNs. The enhanced
      pneumococcal susceptibility of CD73-/- mice was significantly reversed by PMN
      depletion following infection, suggesting that EAD-mediated resistance is largely
      mediated by its effects on PMNs. Finally, CD73-inhibition diminished the ability
      of PMNs to kill pneumococci in vitro, suggesting that EAD alters both the
      recruitment and bacteriocidal function of PMNs. The EAD-pathway may provide a
      therapeutic target for regulating potentially harmful inflammatory host responses
      during Gram-positive bacterial pneumonia. 

PMID- 26313748
TI  - Submental Neck Mass in an Adolescent Female.

PMID- 26313749
TI  - CoGA: An R Package to Identify Differentially Co-Expressed Gene Sets by Analyzing
      the Graph Spectra.
AB  - Gene set analysis aims to identify predefined sets of functionally related genes
      that are differentially expressed between two conditions. Although gene set
      analysis has been very successful, by incorporating biological knowledge about
      the gene sets and enhancing statistical power over gene-by-gene analyses, it does
      not take into account the correlation (association) structure among the genes. In
      this work, we present CoGA (Co-expression Graph Analyzer), an R package for the
      identification of groups of differentially associated genes between two
      phenotypes. The analysis is based on concepts of Information Theory applied to
      the spectral distributions of the gene co-expression graphs, such as the spectral
      entropy to measure the randomness of a graph structure and the Jensen-Shannon
      divergence to discriminate classes of graphs. The package also includes common
      measures to compare gene co-expression networks in terms of their structural
      properties, such as centrality, degree distribution, shortest path length, and
      clustering coefficient. Besides the structural analyses, CoGA also includes
      graphical interfaces for visual inspection of the networks, ranking of genes
      according to their "importance" in the network, and the standard differential
      expression analysis. We show by both simulation experiments and analyses of real
      data that the statistical tests performed by CoGA indeed control the rate of
      false positives and is able to identify differentially co-expressed genes that
      other methods failed. 

PMID- 26313750
TI  - Salvage surgery after failure of endoscopic balloon dilatation versus surgery
      first for ileocolonic anastomotic stricture due to recurrent Crohn's disease.
AB  - BACKGROUND: Both surgical resection and endoscopic balloon dilatation are
      treatment options for ileocolonic anastomotic stricture caused by recurrent
      Crohn's disease unresponsive to medications. Perioperative outcomes of salvage
      surgery owing to failed endoscopic balloon dilatation in comparison with
      performing surgery first for the same indication are unclear. METHODS: An
      analysis of a prospectively maintained Crohn's disease database was carried out
      to compare perioperative outcomes of patients who had surgery for failure of
      endoscopic balloon dilatation with outcomes in patients who underwent resection
      first for ileocolonic anastomotic stricture caused by recurrent Crohn's disease
      between 1997 and 2013. RESULTS: Of 194 patients, 114 (58.8 per cent) underwent
      surgery without previous endoscopic balloon dilatation. The remaining 80 patients
      had salvage surgery after one or more endoscopic balloon dilatations during a
      median treatment span of 14.5 months. Patients in the salvage surgery group had a
      significantly shorter length of anastomotic stricture (P < 0.001). Salvage
      surgery was associated with increased rates of stoma formation (P = 0.030),
      overall surgical-site infection (SSI) (P = 0.025) and organ/space SSI (P =
      0.030). In multivariable analysis, preoperative endoscopic balloon dilatation was
      independently associated with both postoperative SSI (odds ratio 3.16, 95 per
      cent c.i. 1.01 to 9.84; P = 0.048) and stoma diversion (odds ratio 3.33, 1.14 to
      9.78; P = 0.028). CONCLUSION: Salvage surgery after failure of endoscopic balloon
      dilatation is associated with increased adverse outcomes in comparison with
      surgery first. This should be discussed with patients being considered for
      endoscopic balloon dilatation for ileocolonic anastomotic stricture due to
      recurrent Crohn's disease.

PMID- 26313751
TI  - Opioid-Induced Nausea Involves a Vestibular Problem Preventable by Head-Rest.
AB  - BACKGROUND AND AIMS: Opioids are indispensable for pain treatment but may cause
      serious nausea and vomiting. The mechanism leading to these complications is not
      clear. We investigated whether an opioid effect on the vestibular system
      resulting in corrupt head motion sensation is causative and, consequently,
      whether head-rest prevents nausea. METHODS: Thirty-six healthy men (26.6 +/- 4.3
      years) received an opioid remifentanil infusion (45 min, 0.15 MUg/kg/min).
      Outcome measures were the vestibulo-ocular reflex (VOR) gain determined by video
      head-impulse-testing, and nausea. The first experiment (n = 10) assessed outcome
      measures at rest and after a series of five 1-Hz forward and backward head-trunk
      movements during one-time remifentanil administration. The second experiment (n =
      10) determined outcome measures on two days in a controlled crossover design: (1)
      without movement and (2) with a series of five 1-Hz forward and backward head
      trunk bends 30 min after remifentanil start. Nausea was psychophysically
      quantified (scale from 0 to 10). The third controlled crossover experiment (n =
      16) assessed nausea (1) without movement and (2) with head movement; isolated
      head movements consisting of the three axes of rotation (pitch, roll, yaw) were
      imposed 20 times at a frequency of 1 Hz in a random, unpredictable order of each
      of the three axes. All movements were applied manually, passively with amplitudes
      of about +/- 45 degrees. RESULTS: The VOR gain decreased during remifentanil
      administration (p<0.001), averaging 0.92 +/- 0.05 (mean +/- standard deviation)
      before, 0.60 +/- 0.12 with, and 0.91 +/- 0.05 after infusion. The average half
      life of VOR recovery was 5.3 +/- 2.4 min. 32/36 subjects had no nausea at rest
      (nausea scale 0.00/0.00 median/interquartile range). Head-trunk and isolated head
      movement triggered nausea in 64% (p<0.01) with no difference between head-trunk
      and isolated head movements (nausea scale 4.00/7.25 and 1.00/4.5, respectively).
      CONCLUSIONS: Remifentanil reversibly decreases VOR gain at a half-life reflecting
      the drug's pharmacokinetics. We suggest that the decrease in VOR gain leads to a
      perceptual mismatch of multisensory input with the applied head movement, which
      results in nausea, and that, consequently, vigorous head movements should be
      avoided to prevent opioid-induced nausea.

PMID- 26313752
TI  - Can We Predict Oral Antibiotic Treatment Failure in Children with Fast-Breathing
      Pneumonia Managed at the Community Level? A Prospective Cohort Study in Malawi.
AB  - BACKGROUND: Pneumonia is the leading cause of infectious death amongst children
      globally, with the highest burden in Africa. Early identification of children at
      risk of treatment failure in the community and prompt referral could lower
      mortality. A number of clinical markers have been independently associated with
      oral antibiotic failure in childhood pneumonia. This study aimed to develop a
      prognostic model for fast-breathing pneumonia treatment failure in sub-Saharan
      Africa. METHOD: We prospectively followed a cohort of children (2-59 months),
      diagnosed by community health workers with fast-breathing pneumonia using World
      Health Organisation (WHO) integrated community case management guidelines. Cases
      were followed at days 5 and 14 by study data collectors, who assessed a range of
      pre-determined clinical features for treatment outcome. We built the prognostic
      model using eight pre-defined parameters, using multivariable logistic
      regression, validated through bootstrapping. RESULTS: We assessed 1,542 cases of
      which 769 were included (32% ineligible; 19% defaulted). The treatment failure
      rate was 15% at day 5 and relapse was 4% at day 14. Concurrent malaria diagnosis
      (OR: 1.62; 95% CI: 1.06, 2.47) and moderate malnutrition (OR: 1.88; 95% CI: 1.09,
      3.26) were associated with treatment failure. The model demonstrated poor
      calibration and discrimination (c-statistic: 0.56). CONCLUSION: This study
      suggests that it may be difficult to create a pragmatic community-level
      prognostic child pneumonia tool based solely on clinical markers and pulse
      oximetry in an HIV and malaria endemic setting. Further work is needed to
      identify more accurate and reliable referral algorithms that remain feasible for
      use by community health workers.

PMID- 26313753
TI  - High Temperature, High Ambient CO2 Affect the Interactions between Three Positive
      Sense RNA Viruses and a Compatible Host Differentially, but not Their Silencing
      Suppression Efficiencies.
AB  - We compared infection of Nicotiana benthamiana plants by the positive-sense RNA
      viruses Cucumber mosaic virus (CMV), Potato virus Y (PVY), and by a Potato virus
      X (PVX) vector, the latter either unaltered or expressing the CMV 2b protein or
      the PVY HCPro suppressors of silencing, at 25 degrees C vs. 30 degrees C, or at
      standard (~401 parts per million, ppm) vs. elevated (970 ppm) CO2 levels. We also
      assessed the activities of their suppressors of silencing under those conditions.
      We found that at 30 degrees C, accumulation of the CMV isolate and infection
      symptoms remained comparable to those at 25 degrees C, whereas accumulation of
      the PVY isolate and those of the three PVX constructs decreased markedly, even
      when expressing the heterologous suppressors 2b or HCPro, and plants had either
      very attenuated or no symptoms. Under elevated CO2 plants grew larger, but
      contained less total protein/unit of leaf area. In contrast to temperature,
      infection symptoms remained unaltered for the five viruses at elevated CO2
      levels, but viral titers in leaf disks as a proportion of the total protein
      content increased in all cases, markedly for CMV, and less so for PVY and the PVX
      constructs. Despite these differences, we found that neither high temperature nor
      elevated CO2 prevented efficient suppression of silencing by their viral
      suppressors in agropatch assays. Our results suggest that the strength of
      antiviral silencing at high temperature or CO2 levels, or those of the viral
      suppressors that counteract it, may not be the main determinants of the observed
      infection outcomes.

PMID- 26313754
TI  - Epidemiological and Evolutionary Dynamics of Influenza B Viruses in Malaysia,
      2012-2014.
AB  - Epidemiological and evolutionary dynamics of influenza B Victoria and Yamagata
      lineages remained poorly understood in the tropical Southeast Asia region,
      despite causing seasonal outbreaks worldwide. From 2012-2014, nasopharyngeal swab
      samples collected from outpatients experiencing acute upper respiratory tract
      infection symptoms in Kuala Lumpur, Malaysia, were screened for influenza viruses
      using a multiplex RT-PCR assay. Among 2,010/3,935 (51.1%) patients infected with
      at least one respiratory virus, 287 (14.3%) and 183 (9.1%) samples were tested
      positive for influenza A and B viruses, respectively. Influenza-positive cases
      correlate significantly with meteorological factors-total amount of rainfall,
      relative humidity, number of rain days, ground temperature and particulate matter
      (PM10). Phylogenetic reconstruction of haemagglutinin (HA) gene from 168
      influenza B viruses grouped them into Yamagata Clade 3 (65, 38.7%), Yamagata
      Clade 2 (48, 28.6%) and Victoria Clade 1 (55, 32.7%). With neuraminidase (NA)
      phylogeny, 30 intra-clade (29 within Yamagata Clade 3, 1 within Victoria Clade 1)
      and 1 inter-clade (Yamagata Clade 2-HA/Yamagata Clade 3-NA) reassortants were
      identified. Study of virus temporal dynamics revealed a lineage shift from
      Victoria to Yamagata (2012-2013), and a clade shift from Yamagata Clade 2 to
      Clade 3 (2013-2014). Yamagata Clade 3 predominating in 2014 consisted of intra
      clade reassortants that were closely related to a recent WHO vaccine candidate
      strain (B/Phuket/3073/2013), with the reassortment event occurred approximately 2
      years ago based on Bayesian molecular clock estimation. Malaysian Victoria Clade
      1 viruses carried H274Y substitution in the active site of neuraminidase, which
      confers resistance to oseltamivir. Statistical analyses on clinical and
      demographic data showed Yamagata-infected patients were older and more likely to
      experience headache while Victoria-infected patients were more likely to
      experience nasal congestion and sore throat. This study describes the evolution
      of influenza B viruses in Malaysia and highlights the importance of continuous
      surveillance for better vaccination policy in this region.

PMID- 26313755
TI  - Toxicological effects of short-term resuspension of metal-contaminated freshwater
      and marine sediments.
AB  - Sediments in navigation-dominated waterways frequently are contaminated with a
      variety of particle-associated pollutants and are subject to frequent short-term
      resuspension events. There is little information documenting whether resuspension
      of metal-contaminated sediments has adverse ecological effects on resident
      aquatic organisms. Using a novel laboratory approach, the authors examined the
      mobilization of Zn, Cu, Cd, Pb, Ni, and Cr during resuspension of 1 freshwater
      and 2 coastal marine sediments and whether resuspension and redeposition resulted
      in toxicity to model organisms. Sediment flux exposure chambers were used to
      resuspend metal-contaminated sediments from 1 site in Lake DePue, Illinois (USA),
      and 2 sites in Portsmouth Naval Shipyard, Maine (USA). Short-term (4-h)
      resuspension of sediment at environmentally relevant suspended particulate matter
      concentrations (<1 g/L) resulted in metal mobilization to water that was sediment
      and metal specific. Overall, the net release of metals from suspended particles
      was limited, likely because of scavenging by organic matter and Fe oxides that
      formed during sediment interaction with oxic water. Minimal toxicity to organisms
      (survival of Hyalella azteca and Daphnia magna; survival, growth, and tissue
      metal concentration of Neanthes arenaceodentata; bioluminescence of Pyrocystis
      lunula) was observed during 4-h exposure to resuspended sediments and during 4-d
      to 10-d post-exposure recovery periods in uncontaminated water. Redeposited
      suspended particles exhibited increased metal bioavailability and toxicity to H.
      azteca, highlighting the potential for adverse ecological impacts because of
      changes in metal speciation. It is important to consider interactions between
      organisms' life histories and sediment disturbance regimes when assessing risks
      to ecosystems.

PMID- 26313756
TI  - Hepatic Overexpression of Soluble Urokinase Receptor (uPAR) Suppresses Diet
      Induced Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient (LDLR-/-)
      Mice.
AB  - OBJECTIVE: Atherosclerosis, a chronic inflammatory disease, arises from metabolic
      disorders and is driven by inappropriate recruitment and proliferation of
      monocytes / macrophages and vascular smooth-muscle-cells. The receptor for the
      urokinase-type plasminogen activator (uPAR, Plaur) regulates the proteolytic
      activation of plasminogen. It is also a coactivator of integrins and facilitates
      leukocyte-endothelial interactions and vascular smooth-muscle-cell migration. The
      role of uPAR in atherogenesis remains elusive. METHODS AND RESULTS: We generated
      C57Bl6/J low-density lipoprotein receptor (LDL) and uPAR double knockout (uPAR-/
      /LDLR-/-) mice to test the role of uPAR in two distinct atherosclerosis models.
      In LDLR-/- mice, hepatic overexpression following hydrodynamic transfection of
      soluble uPAR that competes with endogenous membrane-bound uPAR was performed as
      an interventional strategy. Aortic root atherosclerotic lesions induced by
      feeding a high-fat diet were smaller and comprised less macrophages and vascular
      smooth-muscle-cells in double knockout mice and animals overexpressing soluble
      uPAR when compared to controls. In contrast, lesion size, lipid-, macrophage-,
      and vascular smooth muscle cell content of guide-wire-induced intima lesions in
      the carotid artery were not affected by uPAR deficiency. Adhesion of uPAR-/-
      macrophages to TNFalpha-stimulated endothelial cells was decreased in vitro
      accompanied by reduced VCAM-1 expression on primary endothelial cells. Hepatic
      overexpression of soluble full-length murine uPAR in LDLR-/- mice led to a
      reduction of diet-induced atherosclerotic lesion formation and monocyte
      recruitment into plaques. Ex vivo incubation with soluble uPAR protein also
      inhibited adhesion of macrophages to TNFalpha-stimulated endothelial cells in
      vitro. CONCLUSION: uPAR-deficiency as well as competitive soluble uPAR reduced
      diet-promoted but not guide-wire induced atherosclerotic lesions in mice by
      preventing monocyte recruitment and vascular smooth-muscle-cell infiltration.
      Soluble uPAR may represent a therapeutic tool for the modulation of
      hyperlipidemia-associated atherosclerotic lesion formation.

PMID- 26313757
TI  - High Throughput Screening Method to Explore Protein Interactions with
      Nanoparticles.
AB  - The interactions of biological macromolecules with nanoparticles underlie a wide
      variety of current and future applications in the fields of biotechnology,
      medicine and bioremediation. The same interactions are also responsible for
      mediating potential biohazards of nanomaterials. Some applications require that
      proteins adsorb to the nanomaterial and that the protein resists or undergoes
      structural rearrangements. This article presents a screening method for detecting
      nanoparticle-protein partners and conformational changes on time scales ranging
      from milliseconds to days. Mobile fluorophores are used as reporters to study the
      interaction between proteins and nanoparticles in a high-throughput manner in
      multi-well format. Furthermore, the screening method may reveal changes in
      colloidal stability of nanomaterials depending on the physicochemical conditions.

PMID- 26313758
TI  - Dally Proteoglycan Mediates the Autonomous and Nonautonomous Effects on Tissue
      Growth Caused by Activation of the PI3K and TOR Pathways.
AB  - How cells acquiring mutations in tumor suppressor genes outcompete neighboring
      wild-type cells is poorly understood. The phosphatidylinositol 3-kinase (PI3K)
      phosphatase with tensin homology (PTEN) and tuberous sclerosis complex (TSC)
      target of rapamycin (TOR) pathways are frequently activated in human cancer, and
      this activation is often causative of tumorigenesis. We utilized the Gal4-UAS
      system in Drosophila imaginal primordia, highly proliferative and growing
      tissues, to analyze the impact of restricted activation of these pathways on
      neighboring wild-type cell populations. Activation of these pathways leads to an
      autonomous induction of tissue overgrowth and to a remarkable nonautonomous
      reduction in growth and proliferation rates of adjacent cell populations. This
      nonautonomous response occurs independently of where these pathways are
      activated, is functional all throughout development, takes place across
      compartments, and is distinct from cell competition. The observed autonomous and
      nonautonomous effects on tissue growth rely on the up-regulation of the
      proteoglycan Dally, a major element involved in modulating the spreading,
      stability, and activity of the growth promoting Decapentaplegic
      (Dpp)/transforming growth factor beta(TGF-beta) signaling molecule. Our findings
      indicate that a reduction in the amount of available growth factors contributes
      to the outcompetition of wild-type cells by overgrowing cell populations. During
      normal development, the PI3K/PTEN and TSC/TOR pathways play a major role in
      sensing nutrient availability and modulating the final size of any developing
      organ. We present evidence that Dally also contributes to integrating nutrient
      sensing and organ scaling, the fitting of pattern to size. 

PMID- 26313759
TI  - A "Sense-and-Treat" Hydrogel Used for Treatment of Bacterial Infection on the
      Solid Matrix.
AB  - A "sense-and-treat" hydrogel is constructed for sensing and inhibiting bacterial
      infection. Without bacteria, the hydrogel emits green fluorescence. With
      bacterial infection, the hydrogel emits red fluorescence and releases Vancomycin
      to kill bacteria. 

PMID- 26313761
TI  - Modulating Biopolymer Electrical Charge to Optimize the Assembly of Edible
      Multilayer Nanofilms by the Layer-by-Layer Technique.
AB  - The aim of this work was to study the influence of biopolymer (alginate, ALG;
      chitosan, CHI) charge on the formation of multilayer nanofilms by the layer-by
      layer (LbL) technique. The electrical charge of ALG and CHI (high, medium, or
      low) was modulated by adjusting the pH of biopolymer solutions. The amount of
      biopolymer deposited in multilayers depended on the charge of ALG and CHI
      solutions. The lower the charge the higher the deposition rate due to the higher
      number of biopolymer molecules needed to neutralize the previous layer. Medium
      and low charge biopolymers led to a drastic change in the wettability of
      multilayers, with ALG layers being strongly hydrophilic and CHI layers strongly
      hydrophobic. The surface zeta-potential alternatively changed from negative to
      positive using ALG or CHI. This effect was more pronounced using highly charged
      biopolymers. Results obtained in this study evidenced that the multilayers
      properties can be tuned by controlling the biopolymer electrical charge. 

PMID- 26313760
TI  - Genome-Wide Identification and Validation of Reference Genes in Infected Tomato
      Leaves for Quantitative RT-PCR Analyses.
AB  - The Gram-negative bacterium Xanthomonas campestris pv. vesicatoria (Xcv) causes
      bacterial spot disease of pepper and tomato by direct translocation of type III
      effector proteins into the plant cell cytosol. Once in the plant cell the
      effectors interfere with host cell processes and manipulate the plant
      transcriptome. Quantitative RT-PCR (qRT-PCR) is usually the method of choice to
      analyze transcriptional changes of selected plant genes. Reliable results depend,
      however, on measuring stably expressed reference genes that serve as internal
      normalization controls. We identified the most stably expressed tomato genes
      based on microarray analyses of Xcv-infected tomato leaves and evaluated the
      reliability of 11 genes for qRT-PCR studies in comparison to four traditionally
      employed reference genes. Three different statistical algorithms, geNorm,
      NormFinder and BestKeeper, concordantly determined the superiority of the newly
      identified reference genes. The most suitable reference genes encode proteins
      with homology to PHD finger family proteins and the U6 snRNA-associated protein
      LSm7. In addition, we identified pepper orthologs and validated several genes as
      reliable normalization controls for qRT-PCR analysis of Xcv-infected pepper
      plants. The newly identified reference genes will be beneficial for future qRT
      PCR studies of the Xcv-tomato and Xcv-pepper pathosystems, as well as for the
      identification of suitable normalization controls for qRT-PCR studies of other
      plant-pathogen interactions, especially, if related plant species are used in
      combination with bacterial pathogens. 

PMID- 26313762
TI  - [Not Available].

PMID- 26313763
TI  - [Not Available].

PMID- 26313764
TI  - Field Investigation of a New Recharge Approach for ASR Projects in Near-Surface
      Aquifers.
AB  - Aquifer storage and recovery (ASR) is the artificial recharge and temporary
      storage of water in an aquifer when water is abundant, and recovery of all or a
      portion of that water when it is needed. One key limiting factor that still
      hinders the effectiveness of ASR is the high costs of constructing, maintaining,
      and operating the artificial recharge systems. Here we investigate a new recharge
      method for ASR in near-surface unconsolidated aquifers that uses small-diameter,
      low-cost wells installed with direct-push (DP) technology. The effectiveness of a
      DP well for ASR recharge is compared with that of a surface infiltration basin at
      a field site in north-central Kansas. The performance of the surface basin was
      poor at the site due to the presence of a shallow continuous clay layer,
      identified with DP profiling methods, that constrained the downward movement of
      infiltrated water and significantly reduced the basin recharge capacity. The DP
      well penetrated through this clay layer and was able to recharge water by gravity
      alone at a much higher rate. Most importantly, the costs of the DP well,
      including both the construction and land costs, were only a small fraction of
      those for the infiltration basin. This low-cost approach could significantly
      expand the applicability of ASR as a water resources management tool to entities
      with limited fiscal resources, such as many small municipalities and rural
      communities. The results of this investigation demonstrate the great potential of
      DP wells as a new recharge option for ASR projects in near-surface unconsolidated
      aquifers.

PMID- 26313765
TI  - Perceptions, Attitudes, and Experience Regarding mHealth Among Homeless Persons
      in New York City Shelters.
AB  - Mobile health may be an effective means of providing access and education to the
      millions of homeless Americans. We conducted semi-structured interviews with 50
      homeless people from different shelters in New York City to evaluate their
      perceptions, attitudes, and experiences regarding mobile health. Participants'
      average age was 51.66 (SD = 11.34) years; duration of homelessness was 2.0 (SD =
      3.10) years. The majority had a mobile phone with the ability to receive and send
      text messages. Most participants attempted to maintain the same phone number over
      time. The homeless were welcoming and supportive of text messaging regarding
      health care issues, including appointment reminders, health education, or
      management of diseases considering their barriers and mobility, and believed it
      would help them access necessary health care. Overwhelmingly they preferred text
      reminders that were short, positively framed, and directive in nature compared to
      lengthy or motivational texts. The majority believed that free cell phone plans
      would improve their engagement with, help them navigate, and ultimately improve
      their access to care. These positive attitudes and experience could be
      effectively used to improve health care for the homeless. Policies to improve
      access to mobile health and adapted text messaging strategies regarding the
      health care needs of this mobile population should be considered. 

PMID- 26313766
TI  - Study on essential oils from the leaves of two Vietnamese plants: Jasminum
      subtriplinerve C.L. Blume and Vitex quinata (Lour) F.N. Williams.
AB  - The essential oil constituents of the leaves of Jasminum subtriplinerve
      (Oleaceae) and Vitex quinata (Verbanaceae) cultivated in Vietnam were analysed by
      gas chromatography--flame ionisation detector (GC-FID) and gas chromatography-
      mass spectrometry (GC-MS) techniques. The main constituents identified in J.
      subtriplinerve were mainly oxygenated monoterpenes represented by linalool
      (44.2%), alpha-terpineol (15.5%), geraniol (19.4%) and cis-linalool oxide (8.8%).
      The quantitative significant components of V. quinata were terpene hydrocarbons
      comprising of beta-pinene (30.1%), beta-caryophyllene (26.9%) and beta-elemene
      (7.4%). The chemical compositions of the essential oils are being reported for
      the first time.

PMID- 26313767
TI  - Hepatocellular Carcinoma With Tumor Thrombus Occupying the Right Atrium and
      Portal Vein: A Case Report and Literature Review.
AB  - Hepatocellular carcinoma (HCC) patients with tumor thrombus extended through the
      major hepatic veins and inferior vena cava into the right atrium (RA) are rare,
      and most cases are considered as the advanced stage with a poor prognosis.We
      report a case of HCC with a tumor thrombus extending into the RA and a tumor
      thrombus in the portal vein. A literature search for case reports was performed
      on PubMed.Compared with the published literature, our case is one of the youngest
      patients, but with the most advanced HCC that invades both the hepatic inflow and
      outflow vasculature. For this patient, we resected the tumor thrombus in the RA
      with the use of cardiopulmonary bypass, and then removed the tumor thrombus in
      the portal vein and ligated the left branch of portal vein. Because of
      insufficient remnant liver volume, microwave ablation and transcatheter arterial
      chemoembolization were performed to control the growth of HCC. The patient
      survived 6 months after surgery.This case suggests that for patients with
      extension of HCC into the RA and portal vein, surgery is a useful therapeutic
      modality, even in case that liver tumor cannot be resected. 

PMID- 26313768
TI  - PRISMA-Extracapsular Dissection Versus Superficial Parotidectomy in Treatment of
      Benign Parotid Tumors: Evidence From 3194 Patients.
AB  - Benign parotid tumor is one of the most common neoplasms in head and neck region.
      Its therapeutic methods have been debatable topics over the past 100 years.
      Recently, some surgeons suggest that extracapsular dissection (ECD) instead of
      superficial parotidectomy (SP) for treatment of benign parotid tumor. This study
      aimed to compare ECD with SP in the treatment of benign parotid tumors by a meta
      analysis.We searched Cochrane Library, PubMed, Embase, Ovid, and Web of Science
      databases on February 14, 2015 for studies that assessed clinical outcomes of SP
      and ECD as surgical techniques for the management of benign parotid tumors.
      Outcome data were evaluated by pooled risk ratio (RR) and corresponding 95%
      confidence interval (CI).After serious scrutiny, a total of 14 cohort studies
      with 3194 patients were included in this meta-analysis. The pooled RR revealed
      that there were no significant difference in tumor recurrence rate between ECD
      and SP (fixed-effect model: RR = 0.71, 95% CI = 0.40-1.27, P = 0.249; random
      effect model: RR = 0.67, 95% CI = 0.38-1.23, P = 0.197). However, there were
      significantly lower incidences of transient facial nerve dysfunction (FND),
      permanent FND, and Frey's syndrome in patients of ECD group compared with SP
      group.ECD might be a good choice in treatment of the benign parotid tumor that
      were mobile, small, located in superficial lobe and without adhesion to facial
      nerve; ECD should be performed by the experienced surgeons with ability of
      dissection facial nerve, who should perform SP if tumor is found adhere to facial
      nerve during an operation; and a multicenter randomized control trial study is
      necessary to decide the optimal treatment of benign parotid tumor.

PMID- 26313769
TI  - Risk of Endometrial Cancer in Women With Pelvic Inflammatory Disease: A
      Nationwide Population-Based Retrospective Cohort Study.
AB  - To investigate the association between pelvic inflammatory disease (PID) and
      endometrial cancer (EC).We conducted a nationwide population-based retrospective
      cohort study, and data were obtained from the National Health Insurance Research
      Database. We defined 41,065 patients with PID as the PID cohort and 82,130
      randomly selected patients as the control cohort through frequency matching by
      age and index year. PID and EC were diagnosed in accordance with the
      International Classification of Diseases, Ninth Revision, and Clinical
      Modification. Cox proportional hazards regression and Kaplan-Meier method were
      used in the analysis.Incidence rates of 16.1 and 9.6 per 100,000 person-years and
      mean follow-up durations of 4.84 and 6.63 years were observed in the PID and non
      PID cohorts, respectively. After adjusting for potential risk factors, the PID
      cohort had a 1.79-fold higher risk of developing EC than the non-PID cohort. The
      incidence of EC increased with age, particularly for those aged >50 years
      (HR=2.45, 95% CI=1.29-4.65). Higher EC risk was also observed in the PID cohort
      with hypertension than in the non-PID cohort.The results of this large-scale
      population-based study showed an increased risk of EC in PID patients,
      particularly in older patients or those with hypertension. Future large-scale
      clinical trials are warranted to clarify the function of medication in PID
      related EC progression.

PMID- 26313770
TI  - Late-Onset Immune Thrombocytopenic Purpura After Withdrawal of Interferon
      Treatment for Chronic Hepatitis C Infection: A Case Report.
AB  - Immune thrombocytopenic purpura (ITP) is a life-threatening complication
      following pegylated interferon alpha (PEG-IFN) plus ribavirin treatment, the
      standard treatment for hepatitis C virus (HCV) infection. We reported a rare case
      with late-onset ITP after withdrawal of PEG-IFN treatment.A 53-year-old male with
      hepatitis C developed massive gum bleeding and a severe, reversible, immune
      thrombocytopenia 2 weeks after cessation of PEG-IFN treatment for HCV due to
      anemia and depression. The platelet count decreased to 4000 cells/MUL. The HCV
      viral load was undetectable at the end of PEG-IFN treatment and during follow-up
      for 5 months. Other potential autoimmune disorders were ruled out. Late-onset ITP
      associated with PEG-IFN treatment was diagnosed.The patient was treated
      successfully with steroid and azathioprine. Platelet count gradually increased to
      117 * 10 cells/MUL on the 18th day after admission.ITP is a rare complication in
      patients with hepatitis C or in patients who received PEG-IFN treatment. The
      particular case supported that it may occur even after withdrawal of PEG-IFN
      treatment. Physicians should be aware of this late-onset complication. 

PMID- 26313771
TI  - Importance of Heparin Provocation and SPECT/CT in Detecting Obscure
      Gastrointestinal Bleeding on 99mTc-RBC Scintigraphy: A Case Report.
AB  - We presented a pediatric case with a history of intermittent melena for 3 years
      because of angiodyplasia of small intestine. The results of frequent upper
      gastrointestinal endoscopies and colonoscopies as well as both Tc-red blood cell
      (RBC) and Meckel's scintigraphies for several times were negative in detection of
      bleeding site. However, Tc-RBC scintigraphy with single-photon emission computed
      tomography (SPECT)/computed tomography (CT) after heparin augmentation detected a
      site of bleeding in the distal ileum which later was confirmed during surgery
      with final diagnosis of angiodysplasia.It could be stated that heparin
      provocation of bleeding before Tc-RBC scintigraphy accompanied by fused SPECT/CT
      images should be kept in mind for management of intestinal bleeding especially in
      difficult cases. 

PMID- 26313772
TI  - Pulmonary Vein Stenosis Complicating Radiofrequency Catheter Ablation: Five Case
      Reports and Literature Review.
AB  - The aim of this study is to characterize the clinical manifestations and features
      of pulmonary vein stenosis (PVS) by retrospectively analyzing clinical data of
      patients in addition to reviewing the literature simultaneously to improve the
      understanding of PVS complicating radiofrequency catheter ablation and to provide
      evidence for early diagnosis and timely treatment.Clinical, imaging, and follow
      up data of 5 patients with PVS-complicating radiofrequency catheter ablation were
      retrospectively analyzed between January 2012 and December 2014 in Shanghai
      Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
      Relevant studies previously reported were also reviewed.Three out of 5 patients
      received pulmonary angiography. The initial symptoms were not specific,
      presenting chest pain in 3 cases, hemoptysis in 2 cases. The average duration
      between radiofrequency ablation to the onset of symptoms was 5.8 months. The
      chest image results were consolidation and pleural effusion mainly. Veins
      distributed in the left lungs were mostly influenced in 4 patients, and the
      inferior veins in 3 patients. Cardiac ultrasound examinations showed pulmonary
      arterial hypertension in 2 patients. Two patients received selective bronchial
      artery embolization after bronchial artery radiography because of hemoptysis. One
      patient underwent video-assisted thoracoscopic biopsy because of the suspicion of
      tumor.PVS is a condition mostly undetected because of its silent manifestations
      and inconsistent follow-up. The accurate clinical diagnosis is very difficult. A
      careful review of medical history and follow-up observation may be useful for all
      the patients who received the radiofrequency catheter ablation to recognize PVS
      in the early stage. 

PMID- 26313773
TI  - Retrospective Analysis of the Efficacy and Safety of Sorafenib in Chinese
      Patients With Metastatic Renal Cell Carcinoma and Prognostic Factors Related to
      Overall Survival.
AB  - Sorafenib has been recommended as first- or second-line treatment for metastatic
      renal cell carcinoma (mRCC) by several guidelines. The objective of this study is
      to evaluate the efficacy of sorafenib monotherapy in Chinese patients with mRCC
      and determine the prognostic clinicopathologic factors associated with survival
      in these patients.This is a single-arm retrospective study conducted in 2
      tertiary medical centers; 140 mRCC patients were enrolled between January 2007
      and June 2014. Sorafenib was administered at a dose of 400 mg twice daily, and
      continued until disease progression, at which point the dose was increased to 600
      or 800 mg twice daily, or the onset of an intolerable adverse drug event (ADE)
      that required dose reduction or temporary suspension of treatment.The primary
      endpoint was overall survival (OS), and the secondary endpoints included
      progression-free survival (PFS), objective response rate (ORR), disease control
      rate (DCR), and safety.The median follow-up time was 32 months. The median OS and
      PFS were 24 months (range, 3-88 months) and 16 months (range, 0-88 months),
      respectively. Patients with clear cell carcinoma had a greater OS (P=0.001)
      whereas sarcomatoid differentiation (P=0.045) and disease progression (P=0.010)
      negatively impacted OS; time from kidney surgery or biopsy to initiation of
      sorafenib treatment was associated with PFS (P=0.027). Efficacy analysis revealed
      that 3 (2.1%) patients achieved complete responses, 28 (20.0%) patients
      experienced partial responses, 88 (62.9%) patients had stable disease, and 21
      (15.0%) patients developed progressive disease. Moreover, the ORR was 22.1%, and
      the DCR was 85.0%. Most ADEs were classified as grades 1 or 2 with only 14
      (10.0%) patients experiencing a severe ADE (grade 3).Sorafenib monotherapy can
      achieve promising OS and PFS for Chinese patients with mRCC, especially in those
      with clear cell carcinoma, with manageable adverse events.

PMID- 26313774
TI  - A Case Report on Dyskinesia Following Rivastigmine Patch 13.3 mg/24 hours for
      Alzheimer's Disease: Perspective in the Movement Disorders Spectrum Following Use
      of Cholinesterase Inhibitors.
AB  - Current reports on movement disorder adverse effects of acetylcholinesterase
      inhibitors only include extrapyramidal symptoms and myoclonus.Here is a case of
      an 81-year-old female Filipino with dementia who presented with first-onset
      generalized choreiform movements.The etiology of the clinical finding of
      dyskinesia was investigated through laboratories, neuroimaging, and
      electroencephalogram, all of which yielded negative results. Review of her
      medications included the rivastigmine (Exelon) patch, which had just been
      increased to 13.3 mg/24-hour-dose 3 months prior. With all other possible causes
      excluded, a trial discontinuation of rivastigmine, showed decreased frequency of
      the dyskinesia 48 hours after, with complete resolution after 6 days, and no
      recurrence since then.This case thus presents a probable association or causality
      between the choreiform movement and rivastigmine at 13.3 mg/24-hour-dose patch
      because of clear temporal proximity, lack of alternative explanations, and a
      reversal of the dyskinesia upon medicament discontinuation. 

PMID- 26313775
TI  - Immediate Postoperative Low Platelet Counts After Living Donor Liver
      Transplantation Predict Early Allograft Dysfunction.
AB  - To investigate whether the platelets can improve liver function by mediating
      liver regeneration. Using a retrospective cohort with 234 consecutive adult-to
      adult living donor liver transplantation recipients, we have discussed the
      relationship between immediate postoperative platelet count and outcome. Patients
      have been stratified into Low Platelet Group (106 patients) with platelet <=68 *
      10/L and High Platelet Group (128 patients) with platelet >68 * 10/L.Low Platelet
      Group has a higher rate of preoperative thrombocytopenia (90.6% vs. 32.8%,
      P<0.001), higher model for end-stage liver disease score (15 vs. 11, P<0.001),
      cirrhosis (86.8% vs. 76.6%, P=0.046), hepatorenal syndrome (18.2% vs. 4.0%,
      P=0.005) and fulminant hepatic failure (26.4% vs. 7.8%, P<0.001). The packed red
      blood cells transfusion (7.5 vs. 5, P = 0.023) and plasma transfusion (1275 mL
      vs. 800 mL, P=0.001) are more in patients with low platelet count. Low Platelet
      Group has a higher early allograft dysfunction (EAD) (22.6% vs. 7.0%, P=0.001)
      and severe complications (22.6% vs. 10.9%, P = 0.016). The 90-day mortality
      between the 2 groups is similar. The multivariate analysis has found that
      postoperative platelet <=68 * 10/L is an independent risk factor for EAD.Platelet
      maybe influences the functional status of the liver by promoting graft
      regeneration after liver transplantation.

PMID- 26313776
TI  - Complete Intestinal Obstruction and Necrosis as a Complication of a
      Ventriculoperitoneal Shunt in Children: A Report of 2 Cases and Systematic
      Literature Review.
AB  - Ventriculoperitoneal (VP) shunt complications are common, but abdominal
      complications are rare. The objective of this report is to present 2 cases of
      intestinal obstruction due to a VP shunt and review the literature for data on
      this rare occurrence.A 4-month-old boy received surgical resection of a
      medulloblastoma and a VP shunt was inserted to manage progressive hydrocephalus.
      Two months later, he was admitted with intermittent vomiting, and plain abdominal
      radiography showed complete intestinal obstruction. Emergency laparotomy revealed
      an adhesive intestinal obstruction around the catheter, and approximately 5 cm of
      necrotic ileum was resected. His recovery was uneventful. In the second case, a 6
      year-old boy was diagnosed with a primary nongerminomatous malignant germ cell
      tumor and a VP shunt was place to treat hydrocephalus. Two weeks after the first
      course of chemotherapy, he went into a coma; computed tomography demonstrated
      enlargement of the tumor and gross total resection was performed. Two weeks
      later, he developed abdominal distention; plain radiography showed intestinal
      obstruction and laparotomy revealed adhesive intestinal obstruction around the
      catheter with 15 cm of necrotic ileum. The necrotic bowel was resected.
      Unfortunately, the patient developed sepsis and despite treatment remained in a
      vegetative state.Medline, Central, Embase, and Google Scholar databases were
      searched up to May 9, 2014, using the terms VP shunt, shunting, and/or intestinal
      obstruction. Only cases involving children or adolescents were included. Eleven
      reports involving patients with abdominal complications resulting from a VP shunt
      for hydrocephalus were identified. The dates of the reports spanned from 1971 to
      2014. Volvulus was the most common cause of VP shunt-related obstruction, and
      mechanical obstruction due to twisting of the catheter the second most common.
      Only 1 case in the literature review was related to intestinal adhesions.
      Treatment in most cases was laparotomy.Although intestinal obstruction is a rare
      complication of a VP shunt, it should be considered in the presence of abdominal
      symptoms and prompt treatment provided to have a good outcome. 

PMID- 26313777
TI  - Synchronous Hepatic Epithelioid Hemangioendothelioma and Hepatocellular
      Carcinoma: First Case Report in the Literature and Challenges.
AB  - We would like to report the first case in English literature, to the best of our
      knowledge, of a synchronous hepatic epithelioid hemangioendothelioma (HEHE) and
      hepatocellular carcinoma (HCC), as well as to address the current trends and
      challenges in the management of HEHE.An otherwise well 58-year-old man was
      referred to his local hepatology service with elevated serum gamma-GT levels.
      Imaging revealed bilobar liver lesions consistent with HEHE, a discrete left lobe
      lesion suspected as HCC, and multiple pulmonary nodules. Biopsies confirmed HEHE
      with pulmonary metastases. After multidisciplinary team discussions, the patient
      was admitted under our team and underwent an uneventful laparoscopic left lateral
      hepatectomy for suspected HCC, which was confirmed histologically.As part of a
      watch-and-wait approach to metastatic HEHE, in the first follow-up (3 months
      postoperatively) the patient was clinically fine and the surveillance CT scan did
      not show recurrent disease.By presenting this case, we aim to raise awareness
      that this rare entity can coexist with others, potentially complicating their
      management. 

PMID- 26313778
TI  - The Preference for Anterior Approach Major Hepatectomy: Experience Over 3 Decades
      and a Propensity Score-Matching Analysis in Right Hepatectomy for Hepatocellular
      Carcinoma.
AB  - Surgical treatment for primary hepatocellular carcinoma (HCC) has progressed
      enormously over time. The aim of this study was to analyze the evolution of
      surgical techniques and outcomes of patients undergoing major right hepatectomy
      (RH) over the last few decades.A retrospective review of 557 consecutive patients
      who had undergone RH for HCC between January 1982 and December 2011 was
      performed. Patients were categorized into subgroups and analyzed according to
      period and surgical approach to hepatectomy. Based on a propensity score-matching
      model, the surgical approach in patients in the second period was also analyzed
      in terms of anterior approach (AA) and conventional approach (CA)-RH.Tumor
      factors remained the most important prognostic factors related to postoperative
      HCC recurrence throughout the 2 periods examined in this study. Comparison of
      patients selected by a propensity score-matching model showed that AA-RH led to
      significantly better outcomes including recurrence-free survival (RFS) (P =
      0.011) and overall survival (OS) (P = 0.012) in patients with HCC as compared
      with CA-RH. The 5-year RFS and OS were 33.4% and 52.2% after AA-RH, and 21.0% and
      36.5% after CA-RH.Major hepatectomy has evolved into a safe procedure that can be
      performed with confidence. RH by an AA has shown several advantages over CA-RH,
      and can thus be recommended as the standard procedure for liver resection in
      patients who require right hepatectomy. 

PMID- 26313779
TI  - Comparison on Clinicopathological Features and Prognosis Between Esophagogastric
      Junctional Adenocarcinoma (Siewert II/III Types) and Distal Gastric
      Adenocarcinoma: Retrospective Cohort Study, a Single Institution, High Volume
      Experience in China.
AB  - The incidence of the EGJA is rapidly increasing. The clinicopathological features
      have not yet been elucidated. The aim of this study was to analyze the
      differences in clinicopathological features and prognosis between patients with
      esophagogastric junctional adenocarcinoma (EGJA) and distal gastric
      adenocarcinoma (DGA).In this retrospective study, 1230 patients who underwent
      gastrectomy between January 2006 and December 2010 in West China Hospital were
      enrolled. Patients were divided into 2 groups based on tumor location.
      Clinicopathological characteristics, postoperative complications, and survival
      outcomes were compared. Univariate and multivariate analysis were also used to
      evaluate the prognostic factors of DGA and EGJA.Patients with gastric
      adenocarcinoma were divided into 2 study groups according to tumor location: 321
      EGJA (26.1%) and 909 DGA (73.9%). Tumors with larger diameter, more advanced pT
      and pN stage were more common in EGJA. Significant differences were revealed in 3
      year overall survival rate (3-YS) between 2 groups: EGJA (57.5%) and DGA (65.5%)
      (P = 0.001), and further analysis indicate that there was also significant
      difference on 3-YS between EGJA (76.9%) and DGA (84.2%) (P = 0.012) in stage II.
      From our multivariate analysis, we found that there were different independent
      prognostic indicators for DGA and EGJA.The clinicopathological features of EGJA
      were strikingly different from DGA and patients with EGJA showed a worse
      prognosis when compared with DGA. The pT stage, pN stage, pM stage, tumor size,
      age, and radical degree were determined to be independent factors of prognosis
      for DGA, while only combined organ resection, pN stage, and pM stage were
      independent prognostic factors for EGJA. 

PMID- 26313780
TI  - A Cross-Sectional Comparison of Perceived Quality of Primary Care by Hypertensive
      Patients in Shanghai and Shenzhen, China.
AB  - Hypertension should be best managed under primary care settings. This study aimed
      to compare, between Shanghai and Shenzhen, the perceived quality of primary care
      in terms of accessibility, continuity, co-ordination, and comprehensiveness among
      hypertensive patients.A cross-sectional study was conducted in Shanghai and
      Shenzhen, China. Multistage random sampling method was used to select 8 community
      health centers. Data from primary care users were collected through on-site face
      to-face interviews using the primary care assessment tool. Good quality standard
      was set as a value of 3 for each attribute and a value of 18 for total score.We
      included 568 patients in Shanghai and 128 patients in Shenzhen. Compared with
      those in Shenzhen, hypertensive patients in Shanghai reported a higher score in
      co-ordination of information (3.37 vs 3.66; P < 0.001), but lower scores in
      continuity of care (3.36 vs 3.27; P < 0.001), and comprehensiveness-service
      provision (3.26 vs 2.79; P < 0.001). There was no statistically significant
      difference in total scores between the 2 cities (18.19 vs 18.15). Over 3-quarters
      of hypertensive patients in both cities reported accessibility (97.2% vs 91.4%)
      and co-ordination of services (76.1% vs 80.5%) under good quality standard, while
      <1-quarter of them rated continuity of care (23.6% vs 22.7%), co-ordination of
      information (4.8% vs 21.1%), and comprehensiveness-service availability (15.1% vs
      25.0%) under that standard.Compared with Shenzhen, the perceived quality of
      primary care for hypertensive patients in Shanghai was better in terms of co
      ordination of information, but poorer on continuity of care and comprehensiveness
      service provision. Our study suggests that there is room for quality improvement
      in both cities.

PMID- 26313781
TI  - Thalamic Reorganization in Chronic Patients With Intracerebral Hemorrhage: A
      Retrospective Cross-Sectional Study.
AB  - The aim of this study was to investigate changes of synaptic area of the
      spinothalamic tract and its thalamocortical pathway (STT) in the thalamus in
      chronic patients with putaminal hemorrhage.Twenty four patients with a lesion in
      the ventral posterior lateral nucleus (VPL) of the thalamus following putaminal
      hemorrhage were recruited for this study. The subscale for tactile sensation of
      the Nottingham Sensory Assessment (NSA) was used for the determination of
      somatosensory function. Diffusion tensor tractography of the STT was
      reconstructed using the Functional Magnetic Resonance Imaging of the Brain
      Software Library. We classified patients according to 2 groups: the VPL group,
      patients whose STTs were synapsed in the VPL; and the non-VPL group, patients
      whose STTs were synapsed in other thalamic areas, except for the VPL.Thirteen
      patients belonged to the VPL group, and 8 patients belonged to the non-VPL group.
      Three patients were excluded from grouping due to interrupted integrity of the
      STTs. The tactile sensation score of the NSA in the non-VPL group (10.50 +/-
      0.93) was significantly decreased compared with that of the VPL group (19.45 +/-
      1.33) (P < 0.05).We found that 2 types of patient had recovered via the VPL area
      or other areas of the STT. It appears that patients who showed shifting of the
      thalamic synaptic area of the STT might have recovered by the process of thalamic
      reorganization following thalamic injury. In addition, thalamic reorganization
      appears to be related to poorer somatosensory outcome. 

PMID- 26313782
TI  - Primary Pulmonary Synovial Sarcoma in a Tertiary Referral Center: Clinical
      Characteristics, CT, and 18F-FDG PET Findings, With Pathologic Correlations.
AB  - The purpose of this study was to describe the patient characteristics, computed
      tomography (CT) and F-fluorodeoxyglucose positron emission tomography (FDG PET)
      findings, and clinical outcomes of primary pulmonary synovial sarcoma (PPSS),
      together with their pathologic correlations. The medical records of 14 patients
      with pathologically proven PPSS in a tertiary hospital from January 1997 to
      December 2014 were retrospectively reviewed. The CT findings were evaluated. The
      maximum standardized uptake value (maxSUV) of the tumors was obtained, and
      clinical outcomes with respect to tumor recurrence and mortality were assessed by
      Kaplan-Meier analysis. The median tumor size was 10.2 cm and the most common
      anatomic location was the lung followed by the pleura/chest wall and mediastinum.
      Most of the tumors appeared as single lesions and had circumscribed margins. All
      the cases showed heterogeneous enhancement with necrotic or cystic portions, and
      intratumoral vessels were frequently seen. Half of the tumors had intratumoral
      calcifications, and tumor rupture, pleural/chest wall extension, and pleural
      effusion occurred frequently. However, lymph node enlargement was rare. The
      median maxSUV of the tumors was 4.35. Patient outcomes with respect to tumor
      recurrence (n = 8, 57.1%) and death (n = 3, 21.4%) were poor despite their young
      age, and the mean follow-up period was 28.5 months.In conclusion, PPSS usually
      occurs in young adults, generally in the lung, presents as a large, circumscribed
      mass, and tumor rupture or extension of the pleura/chest wall may occur. The
      tumors often contain calcifications and vessels; they may exhibit triple
      attenuation on enhanced CT images, and clinical outcomes are poor. 

PMID- 26313783
TI  - Association of Change of Anthropometric Measurements With Incident Type 2
      Diabetes Mellitus: A Pooled Analysis of the Prospective Population-Based CARLA
      and SHIP Cohort Studies.
AB  - Our objective was to investigate the association of change of anthropometric
      measurements and the incidence of type 2 diabetes mellitus (T2DM) within a pooled
      sample of 2 population-based cohorts.A final sample of 1324 women and 1278 men
      aged 31 to 83 years from 2 prospective cohorts in Germany, the CARLA
      (Cardiovascular Disease - Living and Ageing in Halle) and the SHIP study (Study
      of Health in Pomerania), were pooled. The association of change of body weight
      and waist circumference (WC) with incidence of T2DM was assessed by calculating
      sex-specific hazard ratios (HRs). We investigated the absolute change of markers
      of obesity as well as change relative to the baseline value and estimated crude
      and adjusted HRs. Furthermore, we conducted the analyses stratified by obesity
      status and age (<60 vs >=60 years) at baseline.Associations were found for both
      change of body weight and WC and incidence of T2DM in the crude and adjusted
      analyses. In the stratified study sample, those participants with a body mass
      index of <30 kg/m at baseline showed considerably lower HRs compared with obese
      women and men for both weight and WC. In the age-stratified analysis, we still
      found associations between change of weight and WC and incident T2DM with only
      marginal differences between the age groups.Our study showed associations of
      change of weight and WC as markers of obesity with incidence of T2DM. Keeping a
      healthy and primarily stable weight should be the goal for preventing the
      development of T2DM. 

PMID- 26313784
TI  - Effects of RAGE Gene Polymorphisms on the Risk and Progression of Hepatocellular
      Carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a common malignancy of the liver, whose
      heterogeneous incidence reflects genetic variations among individuals in the main
      risk factors. The receptor for advanced glycosylation endproducts (RAGE) is a
      multiligand receptor and known to be implicated in various pathogenic conditions,
      such as diabetes, inflammatory disorder, Alzheimer disease, and cancer. In this
      study, the impact of RAGE gene polymorphisms on the susceptibility to
      hepatocarcinogenesis was explored. Four single-nucleotide polymorphisms (SNPs),
      rs184003 (1704G > T), rs1800624 (-374T > A), rs1800625 (-429T > C), and rs2070600
      (Gly82Ser), as well as 1 gene polymorphism of RAGE gene, a 63 bp deletion allele
      (-407 to -345) were analyzed between 300 cancer-free subjects and 265 HCC cases.
      We detected a significant association of rs1800625 with the increased risk of HCC
      (odds ratio [OR], 2.565; 95% confidence interval [CI], 1.492-4.409 and adjusted
      odds ratio [AOR], 2.568; 95% CI, 1.418-4.653). However, patients who possess at
      least 1 polymorphic allele of rs1800625 are less prone to develop late-stage
      (stage III/IV, OR, 0.502; 95% CI, 0.243-1.037; P = 0.059 and AOR, 0.461; 95% CI,
      0.219-0.970; P = 0.041) and large-size tumors (OR, 0.398; 95% CI, 0.183-0.864; P
      = 0.017 and AOR, 0.351; 95% CI, 0.157-0.781; P = 0.010). Furthermore, individuals
      bearing specific haplotypes of 4 RAGE SNPs tested are more inclined to have HCC.
      In conclusion, our data suggest a correlation of RAGE gene polymorphism rs1800625
      with the early stage of liver tumorigenesis and implicate its protective role in
      the progression of HCC. 

PMID- 26313785
TI  - The Association Between Body Mass Index and All-Cause Mortality in Patients With
      Type 2 Diabetes Mellitus: A 5.5-Year Prospective Analysis.
AB  - Abundances of study in different population have noted that obese cardiovascular
      disease (CVD) patients have a better prognosis than leaner patients, which refer
      to the phenomenon of obesity paradox. However, data on the association between
      body mass index (BMI) and mortality among Asian patients are limited, especially
      in patients with type 2 diabetes mellitus (T2DM). We investigate the association
      between BMI and all-cause mortality in Taiwanese patients with T2DM to define the
      optimal body weight for health.We conducted a longitudinal cohort study of 2161
      T2DM patients with a mean follow-up period of 66.7 +/- 7.5 months. Using Cox
      regression models, BMI was related to the risk of all-cause mortality after
      adjusting all confounding factors.A U-shaped association between BMI and all
      cause mortality was observed among all participants. Those with BMIs <22.5 kg/m
      had a significantly elevated all-cause mortality as compared with those with BMIs
      22.5 to 25.0 kg/m, (BMIs 17.5-20.0 kg/m: hazard ratio 1.989, P < 0.001; BMIs 20.0
      22.5 kg/m: hazard ratio 1.286, P = 0.02), as did those with BMIs >30.0 kg/m (BMIs
      30.0-32.5 kg/m: hazard ratio 1.670, P < 0.001; BMIs 32.5-35.0 kg/m: hazard ratio,
      2.632, P < 0.001). This U-shaped association remained when we examined the data
      by sex, age, smoking, and kidney function.Our study found a U-shaped relationship
      between all-cause mortality and BMI in Asian patients with T2DM, irrespective of
      age, sex, smoking, and kidney function. BMI <30 kg/m should be regarded as a
      potentially important target in the weight management of T2DM.

PMID- 26313786
TI  - Current Status of Breast Reconstruction in Southern China: A 15 Year, Single
      Institutional Experience of 20,551 Breast Cancer Patients.
AB  - The study of this study is to assess the current status and trend of the
      application of breast reconstruction in China.A retrospective review of all
      patients who had received surgical treatment for breast cancer in the Fudan
      University Shanghai Cancer Center between January 1999 and June 2014 was
      performed. The clinicopathological and epidemiological parameters and the follow
      up information of each patient were collected.A total of 20,551 patients with
      20,974 surgeries were identified. Of those, the rates of patients received
      mastectomy, breast conserving therapy, and breast reconstruction were 81.2%
      (17,040 cases), 15.3% (3216 cases), and 3.4% (718 cases), respectively. Skin
      sparing mastectomy with autologous breast reconstruction was algate the dominant
      option for breast reconstruction although a rapid growth in the application of
      prosthetic reconstructions was observed in recent years. The rates of
      complications that required reoperation in patients reconstructed with latissimus
      dorsi myocutaneous flap, pedicled transverse rectus abdominis myocutaneous flap,
      free flaps, and prosthesis were 1.2%, 8.5%, 11.4%, and 10.5%, respectively, while
      the revision rates were 0.7%, 6.1 %, 5.3%, and 2.3%, respectively. Multiple
      regression analysis confirmed that types of surgery did not affect the disease
      free survival of breast cancer patients.Skin-sparing mastectomy with breast
      reconstruction is oncologically safe while achieving satisfactory aesthetic
      outcomes. Autologous reconstruction remains the most commonly used technique
      while there is a rapid increase of prosthetic reconstruction in recent years. The
      low demand for breast aesthetics among Chinese women, defects of healthcare
      system, and the limited availability of recourses impeded the development of
      breast reconstruction techniques in China. 

PMID- 26313787
TI  - The Efficacy of Combining EGFR Monoclonal Antibody With Chemotherapy for Patients
      With Advanced Nonsmall Cell Lung Cancer: A Meta-Analysis From 9 Randomized
      Controlled Trials.
AB  - Although epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs)
      have been proved synergistic effect when combined with cytotoxic agents for
      advanced nonsmall cell lung cancer (NSCLC), the results of relevant clinical
      trials remain controversial. The purpose of this meta-analysis was to assess the
      advantage and toxicity profile of chemotherapy plus EGFR-mAbs versus chemotherapy
      alone for patients with NSCLC.We rigorously searched electronic databases for
      eligible studies reporting EGFR-mAbs combined with chemotherapy versus
      chemotherapy alone for patients with advanced NSCLC. The primary outcome was
      overall survival (OS). Pooled results were calculated using proper statistical
      methods.Nine phase II/III randomized controlled trials involved a total of 4949
      participants were included. In general, compared with chemotherapy alone, the
      addition of EGFR-mAbs significantly improved OS (hazard ratio [HR] = 0.91, 95%
      confidence interval [CI]: 0.86-0.97, P = 0.006), progression-free survival (HR =
      0.83, 95% CI: 0.87-0.98, P = 0.01), response rate (odd ratio [OR] = 1.28, 95% CI:
      1.12-1.47, P = 0.0003), and disease control rate (OR = 1.17, 95% CI: 1.01-1.36, P
      = 0.04). Subgroup analysis showed that apparent OS benefit present in patients
      with squamous NSCLC (HR = 0.83, 95% CI: 0.74-0.93, P = 0.001), and those
      treatment-naive population (HR = 0.88, 95% CI: 0.82-0.95, P = 0.0006). Several
      manageable adverse events were markedly increased by EGFR-mAbs, such as acne-like
      rash, infusion reactions, and diarrhea. The risk for some >=Grade 3 toxicities,
      such as leukopenia, febrile neutropenia, and thromboembolic events were slightly
      increased by the addition of EGFR-mAbs. In general, the toxicities of the
      combination strategy were tolerable and manageable.The addition of EGFR-mAbs to
      chemotherapy provided superior clinical benefit along with acceptable toxicities
      to patients with advanced NSCLC, especially those harboring squamous cancer and
      treatment-naive. Further validation in front-line investigation, proper selection
      of the potential benefit population by tumor histology, and development of
      prognostic biomarkers are warranted for future research and clinical application
      of EGFR-mAbs.

PMID- 26313788
TI  - Correlation Between Tumor Regression Grade and Clinicopathological Parameters in
      Patients With Squamous Cell Carcinoma of the Esophagus Who Received Neoadjuvant
      Chemoradiotherapy.
AB  - The aim of this study was 2-fold: first, to assess the prognostic significance on
      overall survival (OS) of the 3-point tumor regression grade (TRG) in patients
      with esophageal squamous cell carcinoma (ESCC) who received neoadjuvant
      chemoradiotherapy (nCRT); second, to investigate the associations of TRG with the
      clinicopathological characteristics of the study patients.A total of 357 ESCC
      patients were retrospectively enrolled. The 3-point TRG was determined by
      assessing the percentage of viable residual tumor cells (VRTC) in the resected
      specimens as follows: TRG 1, 0% VRTC; TRG 2, 1% to 50% VRTC; and TRG 3, >50%
      VRTC.A TRG of 1, 2, and 3 was found in 32.2%, 38.9%, and 28.9% of the specimens,
      respectively. High TRG values were significantly associated with advanced
      pretreatment clinical stage, longer tumor length, and higher posttreatment tumor
      depth of invasion (yT), the presence of lymph node metastases (LNM), and
      lymphovascular invasion. We observed a stepwise decrease in 5-year OS rates with
      increasing TRG, as follows: 51% for patients with a TRG of 1, 28% for patients
      with a TRG of 2, and 22% for patients with a TRG of 3 (P < 0.001). TRG and LNM
      were independent predictors of OS in multivariate analysis. Notably, the
      prognostic impact of TRG on OS was greater in patients without LNM (P < 0.001)
      and ypT3 disease (P = 0.021).TRG is independently associated with OS in ESCC
      patients treated with nCRT. The interrelationships between TRG, LNM, and depth of
      tumor invasion may improve the prognostic stratification in esophageal cancer. 

PMID- 26313790
TI  - A Case of Plasmodium Falciparum Malaria Presentation.
AB  - New York City is a multicultural city where people of different ethnicities and
      backgrounds from all over the world live together. Of the different ethnicities,
      it is home to a large population of Western African immigrants. This case report
      is that of an elderly female of Western African descent presenting to Lincoln
      Hospitals Emergency Department with fevers and fatigue.The patients travel
      history to Togo, along with her symptoms, resulted in a differential diagnosis
      which included Ebola as well as Malaria. New York City's Department of Health and
      Mental Hygiene was contacted for further clarification of presence of Ebola in
      Togo. The present case report is meant to educate about the presentation,
      hospital course, and differential diagnoses of a patient traveling from Western
      Africa with fever and chills. 

PMID- 26313791
TI  - Who Is Doing the Dance in Epididymis: The Principle of Moblile Echogenicities
      Without Filarial Infection: Case Report.
AB  - The aim of this study was to explore the principle of moblile echogenicities in
      epididymis in patients with a history of postvasectomy or infertility, which were
      reported as the characteristic sonographic sign of filarial infection.We reported
      a 38-year-old man presented with a 3-year history of infertility after marriage.
      Ultrasound imaging revealed an enlarged body in the inner left epididymis along
      with innumerable punctate mobile echogenicities, which showed random to-and-fro
      movements in the left epididymis. This had previously been recognized as the
      sonographic filarial dance sign of live filarial worms or microfilaria. The
      patient subsequently underwent needle aspiration of the left
      epididymis.Histopathological examination confirmed that the mobile echogenicities
      were a large number of macrophages with phagocytized sperm or clumps of
      agglutinated sperm. Our report includes a video clip that will help familiarize
      readers with this phenomenon.Our case highlighted that moblile echogenicities
      should be an important sign for epididymal obstruction to initiate corresponding
      treatment. 

PMID- 26313789
TI  - Cisplatin Nephrotoxicity and Longitudinal Growth in Children With Solid Tumors: A
      Retrospective Cohort Study.
AB  - Cisplatin, a major antineoplastic drug used in the treatment of solid tumors, is
      a known nephrotoxin. This retrospective cohort study evaluated the prevalence and
      severity of cisplatin nephrotoxicity in 54 children and its impact on height and
      weight.We recorded the weight, height, serum creatinine, and electrolytes in each
      cisplatin cycle and after 12 months of treatment. Nephrotoxicity was graded as
      follows: normal renal function (Grade 0); asymptomatic electrolyte disorders,
      including an increase in serum creatinine, up to 1.5 times baseline value (Grade
      1); need for electrolyte supplementation <3 months and/or increase in serum
      creatinine 1.5 to 1.9 times from baseline (Grade 2); increase in serum creatinine
      2 to 2.9 times from baseline or need for electrolyte supplementation for more
      than 3 months after treatment completion (Grade 3); and increase in serum
      creatinine >=3 times from baseline or renal replacement therapy (Grade
      4).Nephrotoxicity was observed in 41 subjects (75.9%). Grade 1 nephrotoxicity was
      observed in 18 patients (33.3%), Grade 2 in 5 patients (9.2%), and Grade 3 in 18
      patients (33.3%). None had Grade 4 nephrotoxicity. Nephrotoxicity patients were
      younger and received higher cisplatin dose, they also had impairment in
      longitudinal growth manifested as statistically significant worsening on the
      height Z Score at 12 months after treatment. We used a multiple logistic
      regression model using the delta of height Z Score (baseline-12 months) as
      dependent variable in order to adjust for the main confounder variables such as:
      germ cell tumor, cisplatin total dose, serum magnesium levels at 12 months,
      gender, and nephrotoxicity grade. Patients with nephrotoxicity Grade 1 where at
      higher risk of not growing (OR 5.1, 95% CI 1.07-24.3, P=0.04). The cisplatin
      total dose had a significant negative relationship with magnesium levels at 12
      months (Spearman r=-0.527, P=<0.001).

PMID- 26313792
TI  - Surgical Treatment of Giant Liver Hemangioma Larger Than 10 cm: A Single Center's
      Experience With 86 Patients.
AB  - The ideal surgical treatment of giant liver hemangioma is still controversial.
      This study aims to compare the outcomes of enucleation with those of resection
      for liver hemangioma larger than 10 cm in different locations of the liver and
      establish the preoperative predictors of increased intraoperative blood
      loss.Eighty-six patients underwent enucleation or liver resection for liver
      hemangioma larger than 10 cm was retrospectively reviewed. Patient demographic,
      tumor characteristics, surgical indications, the outcomes of both surgical
      treatment, and the clinicopathological parameters influencing intraoperative
      blood loss were analyzed.Forty-six patients received enucleation and 40 patients
      received liver resection. Mean tumor size was 14.1 cm with a range of 10-35 cm.
      Blood loss, blood product usage, operative time, hepatic vascular occlusion time
      and frequency, complications and postsurgical hospital stay were similar between
      liver resections and enucleation for right-liver and left-liver hemangiomas.
      There was no surgery-related mortality in either group. Bleeding was more related
      to adjacency of major vascular structures than the size of hemangioma. Adjacency
      to major vascular structures and right or bilateral liver hemangiomas were
      independently associated with blood loss >550 mL (P = 0.000 and 0.042,
      respectively).Both enucleation and liver resection are safe and effective
      surgical treatments for liver hemangiomas larger than 10 cm. The risk of
      intraoperative blood loss is related to adjacency to major vascular structures
      and the location of hemangioma.

PMID- 26313793
TI  - Clinical and Genetic Factors Associated With Thiazide-Induced Hyponatremia.
AB  - Thiazide diuretics are associated with an increased risk of hyponatremia. The aim
      of this study was to investigate possible predictors of thiazide-induced
      hyponatremia.A total of 48 patients admitted to the ward or to the emergency
      department due to severe thiazide-induced hyponatremia (Na < 125 mmol/L) were
      enrolled in our study as the case group. Another 211 hypertensive patients with
      normal sodium levels after treatment with thiazide diuretics were selected as the
      control group. Twelve tag single nucleotide polymorphism markers were selected
      from the Potassium Channel, Inwardly Rectifying Subfamily J, Member 1 (KCNJ1)
      gene: rs1231254, rs2238009, rs1148058, rs675482, rs673614, rs12795437, rs2855800,
      rs2509585, rs3016774, rs881333, rs4529890, and rs7116606. Clinical and genetic
      parameters between patients with thiazide-induced hyponatremia and the control
      group were compared. Logistic regression was used to analyze data.The patients
      with thiazide-induced hyponatremia were older (P < 0.001), predominantly female
      (P = 0.008), had a lower mean body mass index (BMI) (P < 0.001), and more
      commonly used angiotensin II receptor antagonist (P < 0.001) and spironolactone
      (P = 0.007) compared with the control groups. Analysis with multivariate logistic
      regression revealed that age (odds ratio [OR], 1.13; 95% confidence interval
      [CI], 1.08-1.19, P < 0.001), female gender (OR, 4.49; 95% CI, 1.54-13.11, P =
      0.006), BMI (OR, 0.80; 95% CI, 0.69-0.93, P = 0.003), and KCNJ1 rs2509585 C/T or
      T/T polymorphisms (OR, 5.75; 95% CI, 1.25-26.45, P = 0.03) were independent
      predictors for thiazide-induced hyponatremia.Older female patients with lower
      BMIs and KCNJ1 rs2509585 C/T or T/T polymorphisms were more likely to develop
      thiazide-induced hyponatremia.

PMID- 26313794
TI  - Education for Ward Nurses Influences the Quality of Inpatient's Bowel Preparation
      for Colonoscopy.
AB  - Although adequate bowel preparation is a prerequisite for colonoscopy,
      preparation among inpatients is often suboptimal. This study aimed to evaluate
      the impact of ward nurse education on the quality of bowel preparation of
      inpatients.A prospective, double-blinded, non-randomized, controlled study was
      performed. Expert endoscopists provided enhanced education to nurses who belonged
      to an "educated ward" followed by training that was repeated every week for 1
      month. The primary outcome was the quality of the bowel preparation, which was
      based on the Ottawa Bowel Preparation Scale (OBPS). Patient compliance and their
      subjective feelings and the factors affecting inadequate bowel preparation were
      also analyzed.One hundred three inpatients in the educated ward and 102 patients
      in the control ward were enrolled. Baseline data were comparable between the 2
      wards. The mean values of the total OBPS scores were 4.42 +/- 2.23 and 6.15 +/-
      2.38 in the educated and control wards, respectively (P < 0.001). The rate of
      poor preparation (OBPS >= 6) in the educated ward was significantly lower than
      that in the control ward (31.1% vs 58.8%, P < 0.001). Compliance with preparation
      and diet instructions in the educated ward was superior to that in the control
      ward (P<0.001). Control patients were more likely to be anxious before
      colonoscopy (P < 0.001), whereas patients in the educated ward showed higher
      level of satisfaction (P = 0.001) and better sleep quality (P < 0.001). A lack of
      ward nurse education (OR 2.365, P = 0.025), constipation (OR 6.517, P < 0.001),
      and insufficient water ingestion (OR 2.044, P = 0.042) were independently
      associated with inadequate bowel preparation among inpatients.Ward nurse
      education effectively improved the quality of bowel preparation, and relevant
      colonoscopic outcomes among inpatients. Additional efforts are needed to control
      constipation and to encourage additional water ingestion in inpatients for better
      bowel preparation.

PMID- 26313795
TI  - Dietary Patterns and Risk for Metabolic Syndrome in Korean Women: A Cross
      Sectional Study.
AB  - Dietary patterns are a risk factor for metabolic syndrome (MetS). The prevalence
      of MetS has increased in Korea, and this condition has become a public health
      issue. Therefore, the present cross-sectional study aimed to identify the
      associations between dietary patterns and the risk of MetS among Korean women.The
      data of 5189 participants were analyzed to determine dietary intake and
      lifestyle. A principal components analysis was employed to determine participant
      dietary patterns with regard to 106 food items. MetS was diagnosed using the
      National Cholesterol Education Program, Adult Treatment Panel III. Logistic
      regression analyses were applied to evaluate the associations between dietary
      pattern quintiles and MetS and to generate odds ratios (ORs) and 95% confidence
      intervals (CIs) after adjusting for potential confounders.Three dietary patterns
      were identified: "traditional," "western," and "prudent." The "prudent" dietary
      pattern consisted of a high intake of fruits and fruit products as well as nuts,
      dairy, and a low consumption of grains; this pattern was negatively associated
      with the risk of MetS. The highest quintile of the "prudent" dietary pattern was
      significantly less likely to develop MetS (OR: 0.5, 95% CI: 0.36-0.68, P for
      trend <0.001) compared with the lowest quintile. This pattern was also negatively
      associated with all of the MetS diagnostic criteria: abdominal obesity (OR: 0.52,
      95% CI: 0.41-0.65), blood pressure (OR: 0.72, 95% CI: 0.59-0.87), triglycerides
      (OR: 0.67, 95% CI: 0.52-0.85), fasting glucose (OR: 0.64, 95% CI: 0.43-0.95), and
      high-density lipoprotein cholesterol (OR: 0.53, 95% CI: 0.42-0.68). However, the
      "traditional" and "western" dietary patterns were not associated with the risk of
      MetS.The "prudent" dietary pattern was negatively associated with the risk of
      developing MetS among Korean women. 

PMID- 26313796
TI  - Direct Revascularization With the Angiosome Concept for Lower Limb Ischemia: A
      Systematic Review and Meta-Analysis.
AB  - The angiosome concept provides practical information regarding the vascular
      anatomy of reconstructive and vascular surgery for the treatment of peripheral
      arterial occlusive disease and, particularly, critical lower limb ischemia.The
      aim of the study was to confirm the efficacy of direct revascularization with the
      angiosome concept (DR) for lower limb ischemia.Complementary manual searches were
      performed through the Pubmed, Cochrane Library, and EMBASE databases.We searched
      all randomized and nonrandomized studies (NRSs) comparing DR with indirect
      revascularization (IR) (without the angiosome concept) for lower limb ischemia.
      Only 9 nonrandomized controlled retrospective cohort studies were found and
      included. Trials published in any language were included.Primary endpoints were
      time to limb amputation and time to wound healing. Data extraction and trial
      quality assessment were performed by two authors independently. A third author
      was consulted for disagreements settlement and quality assurance.Five NRSs
      involving 779 lower limbs revealed that DR significantly improved the overall
      survival of limbs (hazard ratio [HR] 0.61; 95% confidence interval [CI] = 0.46
      0.80; P < 0.001; I = 0%). In addition, DR significantly improved time to wound
      healing (HR 1.38; 95% CI = 1.13-1.69; P = 0.002; I = 0%, in 5 studies including
      605 limbs).All included studies were retrospective comparative studies, and no
      consensus was obtained in describing wound conditions in the included studies.Our
      results suggested that treatment of lower limb ischemia using DR is more
      effective in salvaging limbs and healing wounds than IR is. Additional randomized
      controlled studies are necessary to confirm these results. 

PMID- 26313797
TI  - A Retrospective Comparison of Trastuzumab Plus Cisplatin and Trastuzumab Plus
      Capecitabine in Elderly HER2-Positive Advanced Gastric Cancer Patients.
AB  - A combination of trastuzumab and cisplatin or trastuzumab and capecitabine has
      been confirmed to be effective for treating adverse effects in with HER2-positive
      advanced gastric cancer (AGC) patients. We retrospectively compared the activity
      and safety of trastuzumab plus cisplatin (HP) and trastuzumab plus capecitabine
      (HX) for elderly HER2-positive AGC patients.Ninety two HER2-positive AGC patients
      were included in this study; of those 48 patients received trastuzumab (course 1,
      8 mg/kg followed by course 2, onward, 6 mg/kg on day 1) plus cisplatin (60 mg/m)
      intravenously on day 1 of a 3-week cycle and 44 patients received trastuzumab
      (course 1, 8 mg/kg; course 2 onward, 6 mg/kg) plus intravenous oral capecitabine
      (1000 mg/m twice daily on days 1-14), every 3 weeks. The primary end point was
      overall survival (OS). The secondary end points included objective response rate
      (ORR), progression-free survival (PFS), and toxicity.The median age was 71 years
      in both groups. The median OS was 15.5 months in the HP group and 17.0 months in
      the HX group, with no significant difference between the 2 groups (P = 0.78).
      There were also no significant differences in PFS (median 6.6 months vs 7.2
      months, respectively; P = 0.90) and ORR (58.3% vs 59.1%, respectively; P = 1.00)
      between the HP group and the HX group. The major grade 3 or 4 adverse events in
      the HP group and the HX group were neutropenia (35.4% vs 29.5%, respectively),
      followed by anorexia (25.0% vs 22.7%, respectively), and anemia (16.7% vs 13.6%,
      respectively), no significant differences were observed.HP and HX were associated
      with similar efficacy and safety in HER2-positive AGC patients.

PMID- 26313798
TI  - Aggressive Locoregional Treatment Improves the Outcome of Liver Metastases from
      Grade 3 Gastroenteropancreatic Neuroendocrine Tumors.
AB  - Grade 3 (G3) gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) are rare,
      and there is no report specifically dealing with patients of liver metastases
      from G3 GEP NETs.From January 2004 to January 2014, 36 conservative patients with
      G3 GEP NET liver metastases were retrospectively identified from 3 hepatobiliary
      centers in China. The clinical features and treatment outcomes were
      analyzed.Aggressive locoregional treatments (LT, including cytoreductive surgery,
      radiofrequency ablation, and liver-directed intra-arterial intervention) and
      systemic therapy (ST) were introduced separately or combined, with 26 (72%)
      patients receiving resection of primary tumor and/or hepatic metastases, 12
      patients receiving non-surgical locoregional interventions (NSLRIs), and 22
      patients receiving certain kind of STs. Median overall survival (OS) was 20.0
      months (95% confidence interval [CI]: 8.9-31.1 months) and survival rates were
      62.6%, 30.1%, and 19.8%, at 1, 3, and 5 years, respectively. The median OS was
      9.0 months (95%CI: 3.3-14.7 months) for patients receiving only STs (n = 6), 19
      months (95%CI: 1.3-36.8 months) for patients receiving LT followed by STs (n =
      16), and 101 months (95%CI: 0.0-210.2 months) for patients receiving only LT (n =
      12). Moreover, compared with those receiving only ST or best supportive care,
      patients given certain types of LTs had higher rates of symptom alleviation (3/8
      versus 20/23). On univariate analysis, positive prognostic factors of survival
      were pancreatic primary tumor (P = 0.013), normal total bilirubin level (P =
      0.035), receiving surgery (P = 0.034), receiving NSLRI (P = 0.014), and sum of
      diameters of remnant tumor < 5 cm (P = 0.008). On multivariate analyses,
      pancreatic primary tumor (P = 0.015), normal total bilirubin level (P = 0.002),
      and sum of diameters of remnant tumor < 5 cm (P = 0.001) remained to be
      independent prognostic factors.For patients with G3 GEP NET liver metastases,
      aggressive LTs may improve clinical outcomes. Larger studies with prospective
      design are warranted to consolidate these results, and to discover the most
      appropriate seletion criteria for patients to undergo different kinds of
      aggressive LTs and to find the most effective combinations, with or without ST.

PMID- 26313799
TI  - A Case Report of Mass-Forming Aspergillus Tracheobronchitis Successfully Treated
      with Voriconazole.
AB  - Aspergillus tracheobronchitis (ATB) represents a rare disease entity accounting
      for 3.5% to 5.0% of cases of invasive aspergillosis. Particularly, mass-forming
      ATB is extremely rare, and clinical reports are limited. Given that the patency
      of the trachea and bronchi are essential for maintaining sufficient airflow, a
      central airway mass originating from an Aspergillus infection is likely to be
      associated with severe clinical manifestations and fatal outcomes. Although
      several therapeutic options for ATB have been suggested, including medication and
      airway interventions, the optimal choice of treatment in diverse clinical
      conditions remains under discussion.We report a case of ATB that initially
      manifested as severe dyspnea and total atelectasis of the left lung in a patient
      with newly detected diabetes.Radiographic study, bronchoscopy, and pathologic
      findings of the lesion revealed mass-forming type of ATB.Interestingly, our
      patient's symptoms dramatically resolved with voriconazole without further
      invasive intervention.This clinical experience highlights the beneficial role of
      voriconazole in the treatment of rare and potentially fatal cases of ATB. 

PMID- 26313800
TI  - Intensive Periodontal Treatment Reduces Risk of Infection-Related Hospitalization
      in Hemodialysis Population: A Nationwide Population-Based Cohort Study.
AB  - Periodontal disease (PD) is prevalent and correlated with malnutrition and
      inflammation in patients on hemodialysis (HD). Periodontal therapy improves
      systemic inflammatory and nutritional markers in HD population. The relationship
      between intensive PD therapy and clinical infectious outcomes in patients on HD
      remains unclear.In total, 4451 patients who underwent HD and intensive PD
      treatment between January 1, 1998 and December 31, 2010 were selected from the
      National Health Insurance Research Database as the case cohort. The comparison
      cohort was selected by matching a patient without PD with each PD treated patient
      at a 1:1 ratio according to a propensity score. The rates of hospitalizations for
      infectious diseases for both cohorts were analyzed and compared.Compared with the
      comparison cohort, the hazard ratio (HR) of hospitalization for overall
      infectious diseases was 0.72 (95% confidence interval [CI] = 0.66-0.78, P <
      0.001) for the intensive PD treatment cohort. The intensive PD treated cohort had
      a significantly lower risk of acute and subacute infective endocarditis (HR =
      0.54, 95% CI = 0.35-0.84, P < 0.01), pneumonia (HR = 0.71, 95% CI = 0.65-0.78, P
      < 0.001), and osteomyelitis (HR = 0.77, 95% CI = 0.62-0.96, P < 0.05) than did
      the comparison cohort.The intensive PD treatment of patients with HD was
      associated with reduced risks of overall infectious diseases, acute and subacute
      infective endocarditis, pneumonia, and osteomyelitis. Our study concurs the role
      of a conventional intervention in enhancing infectious diseases outcomes.

PMID- 26313801
TI  - The Risk of Septicemia in End-Stage Renal Disease With and Without Renal
      Transplantation: A Propensity-Matched Cohort Study.
AB  - End-stage renal disease (ESRD) is a well-known risk factor for septicemia. Renal
      transplantation (RTx) is the treatment of choice for ESRD. However, RTx
      recipients should undergo long-term immunosuppressive therapy. The aim of this
      study was to evaluate the risk of septicemia in ESRD patients with and without
      RTx.This cohort study used the National Health Insurance (NHI) data of Taiwan
      from 2000 to 2010. The RTx group consisted of 3286 RTx recipients. The non-RTx
      comparison group also consisted of 3286 subjects with ESRD matched by propensity
      scores for age, sex, index date, comorbidities, and medications. The subjects
      were followed until the end of 2011 to evaluate the septicemia risk.The risk of
      septicemia was lower in the RTx group than the non-RTx group, with an adjusted
      hazard ratio of 0.73 [95% confidence interval (CI) = 0.64-0.84, P < 0.001]. In
      addition, we observed insignificantly lower intensive care unit (ICU) admission
      rate (35.8% vs. 39.8%) and lower 30-day all-cause mortality rate (17.2% vs.
      18.5%) in the RTx group than the non-RTx group. However, the mean cost for
      septicemia in the RTx group was insignificantly higher than the non-RTx group
      (7175 vs. 6421 USD, P = 0.39).RTx recipients had a significantly reduced risk of
      developing septicemia compared to the propensity-matched non-RTx ESRD patients.
      The ICU admission and 30-day all-cause mortality rates also slightly decreased in
      RTx recipients but without statistical significance. 

PMID- 26313802
TI  - A Retrospective Analysis of 7 Human Immunodeficiency Virus-Negative Infants
      Infected by Penicillium marneffei.
AB  - Infection with Penicillium marneffei has rarely been reported in human
      immunodeficiency virus (HIV)-negative infants. We aimed to determine the
      epidemiological, clinical, pathological, and immunological characteristics of 7
      HIV-negative infants infected by P. marneffei, and to provide insights into its
      diagnosis and treatment.We retrospectively reviewed the cases of 7 HIV-negative
      infants infected by P. marneffei who presented to the First Affiliated Hospital
      of Guangxi Medical University between January 1, 2003 and December 1, 2014. The
      infants' median age was 23.43 months (SD = 8.34), and all lived in Guangxi
      Province in China, where P. marneffei is endemic. The median time from disease
      onset to diagnosis was 2.29 months (SD = 2.12). Of the cases studied, 5 (71.43%)
      had medical histories that included frequent pneumonia or bronchopneumonia,
      thrush, congenital megacolon, glucose-6-phosphate dehydrogenase deficiency, and
      hemophagocytic syndrome. The most common symptoms were fever, cough, and anemia,
      followed by lymphadenopathy, hepatosplenomegaly, and being underweight. Four
      patients had slightly elevated white blood cell counts. The lymphocyte and CD4 T
      cell counts were normal. The CD8 T-cell counts, serum immunoglobulin (Ig) G
      titer, and serum IgA titer were low in 5 patients, and the serum IgM titers were
      high in 3 infants. Caseous necrosis was observed in 3 patients whose lymph nodes
      were affected. One case who received intravenous amphotericin B and 3 cases who
      received intravenous voriconazole improved, and these patients were cured after
      continual treatment with oral voriconazole for 6 or 12 months. The remaining
      patients died before they received antifungal treatment.P. marneffei causes
      severe disease and disseminated infections, and it has high mortality rates in
      HIV-negative infants in endemic areas. P. marneffei susceptibility may be
      associated with immunodeficiencies or immune disorders. In endemic areas,
      clinicians should aware of disseminated P. marneffei infections when infants
      present with serious or recurrent infections, even if they are HIV negative. P.
      marneffei is highly susceptible to amphotericin B and voriconazole. Timely
      diagnosis and treatment can improve patients' prognoses. Intravenous voriconazole
      could be recommended as the initial antifungal agent for HIV-negative infants
      infected by P. marneffei, because of its low nephrotoxicity, high sensitivity,
      and high efficacy levels. 

PMID- 26313803
TI  - Access to Care and Cardiovascular Disease Prevention: A Cross-Sectional Study in
      2 Latino Communities.
AB  - Cardiovascular disease (CVD) is the leading killer of Americans. CVD is
      understudied among Latinos, who have high levels of CVD risk factors. This study
      aimed to determine whether access to health care (ie, insurance status and having
      a usual source of care) is associated with 4 CVD prevention factors (ie, health
      care utilization, CVD screening, information received from health care providers,
      and lifestyle factors) among Latino adults and to evaluate whether the
      associations depended on CVD clinical risk/disease.Data were collected as part of
      a community-engaged food environment intervention study in East Los Angeles and
      Boyle Heights, CA. Logistic regressions were fitted with insurance status and
      usual source of care as predictors of the 4 CVD prevention factors while
      controlling for demographics. Analyses were repeated with interactions between
      self-reported CVD clinical risk/disease and access to care measures.Access to
      health care significantly increased the odds of CVD prevention. Having a usual
      source of care was associated with all factors of prevention, whereas being
      insured was only associated with some factors of prevention. CVD clinical
      risk/disease did not moderate any associations.Although efforts to reduce CVD
      risk among Latinos through the Affordable Care Act could be impactful, they might
      have limited impact in curbing CVD among Latinos, via the law's expansion of
      insurance coverage. CVD prevention efforts must expand beyond the provision of
      insurance to effectively lower CVD rates. 

PMID- 26313804
TI  - The Efficacy of Percutaneous Transhepatic Gallbladder Drainage on Acute
      Cholecystitis in High-Risk Elderly Patients Based on the Tokyo Guidelines: A
      Retrospective Case-Control Study.
AB  - To evaluate the efficacy of percutaneous transhepatic gallbladder drainage (PTGD)
      for high-risk elderly patients with acute cholecystitis.Retrospective analysis of
      159 acute cholecystitis patients who were admitted to General Surgery Division
      III of the First Affiliated Hospital of Dalian Medical University between January
      2005 and November 2012. A total of 123 patients underwent laparoscopic
      cholecystectomy (LC), and 36 received only PTGD treatment. The LC patients were
      divided into 3 groups based on their preoperative treatment: group A, emergency
      patients (33 patients); group B (26 patients), patients who were treated with
      PTGD prior to LC; and group C (64 patients), patients who received nonsurgical
      treatment prior to LC. General conditions, LC surgery duration, intraoperative
      blood loss, rate of conversion to open surgery, incidence of postoperative
      complications, total fasting time, and total hospitalization time were analyzed
      and compared among the 3 groups.The remission rates of patients in the PTGD
      treatment groups (including group B and PTGD treatment only group) were
      significantly higher within 24 and 48 hours than those of patients who received
      nonsurgical treatment prior to LC (P < 0.05). Among the patients in the 3 surgery
      groups, the operation conversion rate (19.2%) of group B was significantly higher
      than that of group A (3.0%) and group C (1.6%) (P < 0.05). The total
      hospitalization time of the patients in group B (18.5 +/- 4.5 days) was longer
      than that of the patients in group A (8.2 +/- 3.9 days) and group C (10.5 +/- 6.4
      days). The total fasting time of the patients in group A (2.4 +/- 1.2 days) was
      significantly shorter than that of those in group B (4.1 +/- 1.7 days) and group
      C (3.4 +/- 2.7 days) (P < 0.05).For high-risk elderly patients, if there is any
      emergency surgery contraindication, PTGD therapy may be safe and effective and
      can relieve the symptoms within a short time. For acute cholecystitis patients
      without surgery contraindications, emergency surgery should be performed as soon
      as possible after diagnosis. 

PMID- 26313805
TI  - Primary Indeterminate Dendritic Cell Tumor of Skin Correlated to Mosquito Bite.
AB  - Primary indeterminate dendritic cell tumor (IDCT) is an extremely neoplastic
      dendritic cell disorder. Little is known about its pathogenesis, etiology, and
      prognostic factors because of its rarity. Herein, we present a case report of a
      skin IDCT that arose in mosquito bite and discuss the correlation between
      hypersensitivity to mosquito bites and leukemia/lymphoma.A 28-year old man
      presented with multiple widespread cutaneous plaques and nodules 8 months after
      being bitten by a mosquito on his back. Dermatological examination revealed
      multiple skin-colored, well-demarcated plaques and nodules measuring
      approximately 0.5 to 1.8 cm in diameter all over the body. A biopsy of the skin
      lesion was taken. Morphologically, the dermis was effaced by round or polygonal
      cells with oval nuclei and abundant eosinophilic cytoplasm, arranged in nests and
      in some areas in a sheet-like pattern. The tumor cells were positive for CD68,
      CD1a, and S-100, whereas negative for Langerin and lack Birbeck granules
      ultrastructurally. A diagnosis of IDCT was made. No treatment was given. The
      patient was alive with spontaneous disease regression after 17 months of follow
      up.IDCT is an extremely rare disease and may be associated with mosquito bite. 

PMID- 26313806
TI  - Case Report: Explantation of A Binkhorst Iridocapsular Lens >30 Years After
      Implantation in an Eye With Pseudoexfoliation Syndrome.
AB  - An 86-year-old man with a Binkhorst 2-loop intraocular lens (IOL) that was
      implanted in the pupillary sphincter 33 years earlier was examined. The pupil of
      the implanted eye with the Binkhorst IOL was irregular and the eye had
      pseudoexfoliation (PEX) syndrome. Pupillary erosion resulted from rubbing of the
      IOL edge against the pupillary sphincter with PEX material. The IOL was removed
      because of visual distortion and intense pseudophakodonesis. Gross and light
      microscopic analyses showed no irido-fibro-lenticular adhesions over the lens or
      fragments of iris tissue attached to the lens. Scanning electron microscopy
      showed several pores of different sizes. No inflammatory cells were present,
      suggesting that the IOL was well tolerated.The case suggested that the pupillary
      ruff was not a good location for implantation of an IOL in an eye with PEX.
      Caution is recommended before implanting or suturing an IOL close to the
      pupillary border in eyes with PEX during cataract surgery. 

PMID- 26313807
TI  - Impact of Admission Systolic Blood Pressure and Antecedent Hypertension on Short
      Term Outcomes After ST-Segment Elevation Myocardial Infarction: Strobe-Compliant
      Article.
AB  - We evaluated the combined effect of admission systolic blood pressure (SBP) and
      antecedent hypertension on short-term outcomes in patients with ST-segment
      elevation myocardial infarction (STEMI). Data were derived from a multicenter
      survey of 7303 consecutive patients with STEMI. Patients were divided into 4
      groups according to different blood pressure status: high SBP without
      hypertension, high SBP with hypertension, low SBP without hypertension, and low
      SBP with hypertension. The primary endpoints were 7 and 30-day all-cause
      mortality. The prevalence of hypertension was 40.7%, and the best cutoff of
      admission SBP for predicting 30-day mortality was 108 mmHg by receiver-operating
      characteristic curve. Patients with hypertension were older, more often female,
      also had longer onset-to-admission time, more comorbidities, and higher Killip
      class. Patients with both low SBP (<=108 mmHg) and hypertension group had
      significantly higher 7 and 30-day mortality than those in other groups (all P <
      0.001). After multivariate adjustment, low SBP with hypertension group was still
      an independent risk factor for predicting 7-day mortality (hazard ratios [HR]
      1.86, 95% confidence interval [CI] 1.41-2.46; P < 0.001) and 30-day mortality (HR
      1.88, 95% CI 1.46-2.43; P < 0.001). In patients with SBP > 108 mmHg, a history of
      hypertension could increase the risk of 30-day mortality by 27% (HR 1.00 vs 1.27,
      P = 0.012), while in patients with SBP <= 108 mmHg, this increased risk reached
      to 37% (HR 1.51 vs 1.88, P < 0.001). In conclusion, low admission SBP was the
      relatively dominant contributor for predicting 7 and 30-day all-cause mortality,
      and a concurrent antecedent hypertension increased the corresponding risk of
      mortality. 

PMID- 26313808
TI  - Heme Oxygenase-1 and 2 Common Genetic Variants and Risk for Restless Legs
      Syndrome.
AB  - Several neurochemical, neuropathological, neuroimaging, and experimental data,
      suggest that iron deficiency plays an important role in the pathophysiology of
      restless legs syndrome (RLS). Heme-oxygenases (HMOX) are an important defensive
      mechanism against oxidative stress, mainly through the degradation of heme to
      biliverdin, free iron, and carbon monoxide. We analyzed whether HMOX1 and HMOX2
      genes are related with the risk to develop RLS.We analyzed the distribution of
      genotypes and allelic frequencies of the HMOX1 rs2071746, HMOX1 rs2071747, HMOX2
      rs2270363, and HMOX2 rs1051308 SNPs, as well as the presence of Copy number
      variations (CNVs) of these genes in 205 subjects RLS and 445 healthy controls.The
      frequencies of rs2071746TT genotype and rs2071746T allelic variant were
      significantly lower in RLS patients than that in controls, although the other 3
      studied SNPs did not differ between RLS patients and controls. None of the
      studied polymorphisms influenced the disease onset, severity of RLS, family
      history of RLS, serum ferritin levels, or response to dopaminergic agonist,
      clonazepam or GABAergic drugs.The present study suggests a weak association
      between HMOX1 rs2071746 polymorphism and the risk to develop RLS in the Spanish
      population. 

PMID- 26313809
TI  - An Elevated Glycemic Gap is Associated With Adverse Outcomes in Diabetic Patients
      With Community-Acquired Pneumonia.
AB  - Several studies argue against the association between admission hyperglycemia and
      adverse outcomes in infected diabetic patients. When investigating the
      association, it is necessary to consider preexisting hyperglycemia. The objective
      of this study was to assess whether stress-induced hyperglycemia, determined by
      the glycemic gap between admission glucose levels and A1c-derived average glucose
      levels adversely affects outcomes in diabetic patients admitted to hospital with
      community-acquired pneumonia (CAP).We retrospectively analyzed the glycemic gap
      and adverse outcomes of diabetic patients hospitalized because of CAP from June
      1, 2007 to August 31, 2012 in single medical center in Taiwan.A total of 203
      patients admitted with principal diagnosis of CAP and available data of glycemic
      gap.Patients with glycemic gaps >=40 mg/dL had greater AUROC values for the
      development of adverse outcomes compared with acute hyperglycemia and long-term
      glycemic controls. Patients with an elevated glycemic gap had an odds ratio of
      3.84 for the incidence of combined adverse outcomes. Incorporation of the
      glycemic gap into pneumonia severity index, CURB-65 or SMART-COP scores,
      increased the discriminative performance of predicting the development of adverse
      outcomes.Glycemic gaps were associated with adverse outcomes of diabetic CAP
      patients. The discriminative performance of the calculated glycemic gaps was
      comparable with those of current clinical scoring systems and may further
      increase the AUROC of each system. 

PMID- 26313810
TI  - Sensitivity and Specificity of a Novel Approach to Confirm the Depth of the
      Endotracheal Tube: A Pilot Study.
AB  - This study aimed to explore the sensitivity and specificity an approach to
      confirm the depth of the endotracheal tube. It was a prospective, diagnostic
      study (Registration number: chiCTR-TRC-14005170) conducted in the Department of
      Anesthesiology of West China Hospital. A total of 100 patients underwent general
      anesthesia were included. The distance between the upper margin of the cuff and
      the manubriosternal joint (CM) and the distance between the upper margin of the
      cuff and the carina (CC) were measured. The accuracy of the confirmed approach
      against fiberoptic bronchoscopy (FOB) was evaluated. Sensitivity, specificity,
      positive predictive value (PPV), and negative predictive value (NPV) were
      calculated. The correlation and agreement between CM and CC were explored.The
      sensitivity, specificity, positive predictive value (PPV), and negative
      predictive value (NPV) were determined to be 94.74% (95% CI: 87.07-98.55%),
      79.17% (95% CI: 57.85-92.87%), 93.51% (95% CI: 85.49-97.86%), 82.61% (95% CI:
      61.22%-95.05%), respectively. The kappa value was 0.75 (95% CI: 0.60-0.90). There
      was a significant correlation between CM and CC (P < 0.001) with a correlation
      coefficient of 0.91(95% CI: 0.87-0.94). Bland and Altman plots also demonstrated
      a good agreement between the CM and CC. This novel method may be used to confirm
      the depth of the endotracheal tubes. 

PMID- 26313811
TI  - Meeting American Geriatrics Society Competencies: Are Residents Meeting
      Expectations for Quality Care of Older Adults?
AB  - In order to determine how often internal medicine and family medicine residents
      performed specific actions related to the geriatric competencies established by
      the American Geriatrics Society (AGS) when caring for older hospitalized adults,
      a cross-sectional anonymous survey of residents at the University of North
      Carolina, University of Washington, Wake Forest University, Duke University, and
      Emory University was undertaken. Data on frequency of self-reported behaviors
      were analyzed, with comparisons made for different levels of training,
      institution, and program. A total of 375 residents responded for an overall
      response rate of 48%. Residents reported that they often do not demonstrate all
      of the AGS recommended core competencies when caring for older adults in the
      hospital setting. Residents report more frequently performing activities that are
      routinely integrated into hospital systems such as reviewing medication lists,
      working with an interdisciplinary team, evaluating for inappropriate bladder
      catheters, and evaluating for pressure ulcers. There were no consistent
      differences between institutions and only minor differences noted between Family
      Medicine and Internal Medicine residents. Operationalizing core competencies by
      integrating them into hospital systems' quality process indicators may prompt
      more consistent high-quality care and ensure systems support residents'
      competence. 

PMID- 26313812
TI  - Heart rate variability after myocardial infarction: what we know and what we
      still need to find out.
AB  - Heart rate variability (HRV) is represented by the variation of the time
      intervals between consecutive heartbeats or the instantaneous heart rates, and
      can be assessed with linear and non-linear parameters. It is a sensitive
      indicator of an overall system complexity and adaptability and can be used to
      diagnose the autonomic dysfunction and quantify the associated risk in a variety
      of cardiac and non-cardiac disorders. The aim of this review is to summarize the
      current literature on the value of HRV in predicting the risk of long-term all
      cause, cardiac, and arrhythmic mortality in survivors of myocardial infarction
      (MI). We also emphasize the lack of evidence on the role of therapeutic
      interventions such as medications, bio-behavioral treatments, cardiac
      rehabilitation, and exercise, in modifying the HRV in post-MI patients. 

PMID- 26313813
TI  - May biscuits contribute to iron balance? An observation in children with juvenile
      idiopatic arthritis.
AB  - Within an observational open study on the effects of a scheduled dosage of
      biscuits with iron, children with juvenile idiopathic arthritis were either
      supplemented with biscuits supplying iron fumarate (median 3.6 mg per day) or
      left to their customary dietary habits. After 4 months, supplemented children
      showed a more favourable percentage change of blood haemoglobin, while ferritin
      levels (markers of inflammation) remained stable. We conclude that the supply of
      iron with available dietary products may contribute to an adequate iron status in
      children with chronic inflammatory disorders in a stable situation.

PMID- 26313815
TI  - Beyond limitations: Improving how we handle uncertainty in health professions
      education research.
AB  - The researchers' assumptions invariably influence research outcomes. This is true
      for both qualitative and quantitative studies. Assumptions or choices regarding
      underlying theories, causal relations, study setting and population, sampling
      strategies, participant non-response, data collection, data analysis, and
      researchers' perceptions and interpretations of results are among factors that
      can induce uncertainty in research findings. Researchers tend to treat these
      factors as potential study limitations, but how they may impact research findings
      is rarely explicated and, therefore, mostly unknown. In this article, we approach
      uncertainty as unavoidable in research and argue that communicating about
      uncertainty can inform researchers, policy makers and practitioners about the
      validity and applicability of the study findings for their interests and
      contexts. We illustrate approaches to address, interpret, and explicate
      uncertainty in medical education research in both qualitative and quantitative
      paradigms. Across research paradigms, we call on researchers to consider the
      uncertainty in their research findings, employ appropriate methods to explore its
      extent and effects in their work, and communicate it explicitly in their research
      papers. This will help to advance our understanding of the nature and
      implications of the emerging knowledge in our field. 

PMID- 26313814
TI  - "CLASPing" tungsten's effects on microtubules with "PINs".
AB  - Tungsten, supplied as sodium tungstate, inhibits root elongation in Arabidopsis
      thaliana, which has been attributed to a diminishing of PIN2 and PIN3 auxin
      efflux carriers. In this work, we sought to analyze the effect of tungsten on
      cortical microtubules and CLASP (Cytoplasmic Linker Associated Protein), which
      are also involved in the anisotropic cell expansion of root cells. Seedlings
      grown in a tungsten-free substrate for 4 d and then transplanted into a tungsten
      containing substrate exhibited randomly oriented microtubules in a time-dependent
      manner. While tungsten had no effect on roots treated for 3 h, microtubule
      alignment was obviously affected in the transition and elongation zones after a
      6, 12, 24, 48 h tungsten treatment, at prolonged tungsten administrations and in
      seedlings grown directly in the presence of tungsten. This change in microtubule
      orientation may be associated with the reduction of CLASP protein expression
      induced by tungsten, as evidenced in experiments with plants expressing the CLASP
      GFP protein. A possible mechanism, by which the coordinated functions of CLASP,
      PIN2 and microtubules are affected, as revealed by inhibited root growth, is
      discussed.

PMID- 26313816
TI  - Clinical management of electromagnetic interferences in patients with pacemakers
      and implantable cardioverter-defibrillators: review of the literature and focus
      on magnetic resonance conditional devices.
AB  - The number of cardiac implantable electronic devices (CIEDs) has greatly
      increased in the last 10 years. Many electronic devices used in daily activities
      generate electromagnetic interferences (EMIs) that can interact with CIEDs. In
      clinical practice, it is very important to know the potential sources of EMIs and
      their effect on CIEDs in order to understand how to manage or mitigate them. A
      very important source of EMI is magnetic resonance (MR), which is considered
      nowadays the diagnostic gold standard for different anatomical districts. In this
      review, we focused on the effects of EMI on CIEDs and on the clinical management.
      Moreover, we made a clarification about MR and CIEDs.In patients with CIEDs, EMIs
      may cause potentially serious and even life-threatening complications
      (inappropriate shocks, device malfunctions, inhibition of pacing in pacemaker
      dependent patients) and may rarely dictate device replacement. The association of
      inappropriate shocks with increased mortality highlights the importance of
      minimizing the occurrence of EMI. Adequate advice and recommendations about the
      correct management of EMIs in patients with CIEDs are required to avoid all
      complications during hospitalization and in daily life. Furthermore, the article
      focused on actual management about MR and CIEDs. 

PMID- 26313817
TI  - Self-diffusion, velocity cross-correlation, distinct diffusion and resistance
      coefficients of the ionic liquid [BMIM][Tf2N] at high pressure.
AB  - Ion self-diffusion coefficients (DSi) have been measured for the ionic liquid 1
      butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)amide [BMIM][Tf2N] at
      pressures to 200 MPa between 25 and 75  degrees C and at 0.1 MPa between 10 and
      90  degrees C. Self-diffusion coefficients are reported for 1-ethyl-, 1-hexyl-
      and 1-octyl-3-methylimidazolium bis(trifluoromethanesulfonyl)amide salts at 0.1
      MPa, supplemented by viscosity, electrical conductivity and density measurements.
      Velocity cross-correlation (VCC, fij) and distinct diffusion coefficients (D) are
      calculated from the data. Both DSi and D are analysed in terms of (fractional)
      Stokes-Einstein-Sutherland (SES) equations. SES and Walden plots show almost
      identical slopes, with high-pressure isotherms and the atmospheric pressure
      isobar falling on common, single lines for each property for [BMIM][Tf2N]. SES
      plots for the anion self-diffusion coefficients for the [RMIM][Tf2N] (R = alkyl)
      series are coincident, whereas those for the cations depend on their alkyl
      substitution, as do the Walden plots. In common with other [Tf2N](-) salts, the
      VCC follow the order f-- < f++ < f+-. The Nernst-Einstein deviation parameter
      Delta for [BMIM][Tf2N] is independent of temperature and pressure. Those for the
      other [Tf2N](-) salts are independent of temperature. Delta increases in
      magnitude with increasing alkyl chain length on the cation. The transport
      properties of [BMIM][Tf2N] are re-examined in terms of density scaling using
      reduced conductivities and reduced molar conductivities for the first time.
      Identical scaling parameters (gamma) are obtained for the several reduced
      transport properties. This result is supported by data for other ionic liquids.
      It is suggested that the gamma for ionic liquids may depend on packing fraction. 

PMID- 26313818
TI  - Aesthetic Refinement of the Abdominal Donor Site after Autologous Breast
      Reconstruction.
AB  - BACKGROUND: The abdominal donor site has consistently demonstrated excellent
      aesthetic outcomes when used for autologous breast reconstruction. However, a
      consistent point of dissatisfaction is the location and appearance of the
      abdominal donor-site scar, which can be a frequent cause of distress for the
      patient. The authors consider the appearance of the donor-site to be as important
      to the overall reconstructive effort as that of the breast, and believe it
      worthwhile to achieve an aesthetically pleasing result. Thus, the authors present
      here their technique for aesthetic revision of the abdominal donor site after
      autologous breast reconstruction. METHODS: This is a series of 51 patients who
      underwent autologous tissue breast reconstruction with deep inferior epigastric
      perforator flaps. All patients subsequently underwent abdominal donor-site
      revision during the second stage of their reconstruction, including excision and
      lowering of the abdominal scar, and liposuction of the abdomen and mons pubis to
      achieve optimum contouring. RESULTS: The donor-site scars were lowered an average
      of 5.93 cm (range, 5 to 7 cm). The average procedural time was 27 minutes. No
      wound dehiscence, seromas, hematomas, or infections were reported
      postoperatively. CONCLUSIONS: With this report, the authors put forth a new
      obtainable standard for autologous tissue breast reconstruction donor-site
      aesthetics, and propose a conceptual shift that includes the trunk aesthetic unit
      as an integral part of the overall reconstructive outcome. The authors' results
      here demonstrate that this is a safe, successful, and reproducible procedural
      adjunct to the second stage of breast reconstruction.

PMID- 26313819
TI  - Is There a Safe Lipoaspirate Volume? A Risk Assessment Model of Liposuction
      Volume as a Function of Body Mass Index.
AB  - BACKGROUND: No concrete data exist to support a specific volume at which
      liposuction becomes unsafe; surgeons rely on their own estimates, professional
      organization advisories, or institutional or government-imposed restrictions.
      This study represents the first attempt to quantify the comprehensive risk
      associated with varying liposuction volumes and its interaction with body mass
      index. METHODS: Suction-assisted lipectomies were identified from the Tracking
      Operations and Outcomes for Plastic Surgeons database. Multivariate regression
      models incorporating the interaction between liposuction volume and body mass
      index were used to assess the influence of liposuction volume on complications
      and to develop a tool that returns a single adjusted odds ratio for any
      combination of body mass index and liposuction volume. Recursive partitioning was
      used to determine whether exceeding a threshold in liposuction volume per body
      mass index unit significantly increased complications. RESULTS: Sixty-nine of
      4534 patients (1.5 percent) meeting inclusion criteria experienced a
      postoperative complication. Liposuction volume and body mass index were
      significant independent risk factors for complications. With progressively higher
      volumes, increasing body mass index reduced risk (OR, 0.99; 95 percent CI, 0.98
      to 0.99; p = 0.007). Liposuction volumes in excess of 100 ml per unit of body
      mass index were an independent predictor of complications (OR, 4.58; 95 percent
      CI, 2.60 to 8.05; p < 0.001). CONCLUSIONS: Liposuction by board-certified plastic
      surgeons is safe, with a low risk of life-threatening complications. Traditional
      liposuction volume thresholds do not accurately convey individualized risk. The
      authors' risk assessment model demonstrates that volumes in excess of 100 ml per
      unit of body mass index confer an increased risk of complications. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 26313820
TI  - The Caudal Septum Columellar Strut Graft: An Alternative for Tip Support.
AB  - The authors describe a convenient option for obtaining a columellar strut graft
      without the need for harvesting septal or auricular cartilage. Its utility has
      been shown by use in almost 10 percent of 569 patients in the senior author's
      (D.A.H.) series. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

PMID- 26313821
TI  - The Seesaw Technique for Correction of Vertical Alar Discrepancy.
AB  - Alar vertical discrepancy including alar base has been viewed as one of the most
      challenging reconstructive problems in rhinoplasty. The authors have created a
      simple technique that consistently gives aesthetically acceptable results. The
      authors have designed the seesaw technique to correct alar discrepancy (type 1 to
      3). Type 1 has been used in 14 patients, type 2 has been used in three patients,
      and type 3 has been used in seven patients. Alar discrepancy was corrected
      satisfactorily in all cases, with good cosmetic outcome. One case required scar
      revision and another case required revision for overcorrection; satisfactory
      results were ultimately achieved in both cases. This new technique is quite easy
      to design and is effective in the correction of alar discrepancy. It yields good
      postoperative results along with satisfactory aesthetic outcomes. 

PMID- 26313822
TI  - Discussion: The Seesaw Technique for Correction of Vertical Alar Discrepancy.

PMID- 26313823
TI  - Natural Killer Cells Differentiate Human Adipose-Derived Stem Cells and Modulate
      Their Adipogenic Potential.
AB  - BACKGROUND: Natural killer cells are thought to represent more than 30 percent of
      all lymphocytes within the stromal vascular fraction of lipoaspirates. However,
      their physiologic interaction with adipocytes and their precursors has never been
      specifically examined. The authors hypothesized that natural killer cells, by
      means of cytokine secretion, are capable of promoting the differentiation of
      adipose-derived stem cells. METHODS: Human natural killer cells purified from
      healthy donors' peripheral blood mononuclear cells were activated with a
      combination of interleukin-2 and anti-CD16 monoclonal antibody; natural killer
      cell supernatant was collected. Adipose-derived stem cells isolated from raw
      human lipoaspirates from healthy patients were treated with growth media, growth
      media with natural killer cell supernatant, adipogenic media, and adipogenic
      media with natural killer cells supernatant. Flow cytometric analysis was
      performed on cells using antibodies against B7H1, CD36, CD44, CD34, CD29, and MHC
      1. Adipogenic-related gene expression (PPAR-gamma, LPL, GPD-1, and aP2) was
      assessed. Oil Red O staining was performed as a functional assay of adipocyte
      differentiation and adipogenesis. RESULTS: Adipose-derived stem cells maintained
      in growth media with natural killer cell supernatant lost markers of "stemness,"
      including CD44, CD34, and CD29; and expressed markers of differentiation,
      including B7H1 and MHC-1. Adipose-derived stem cells treated with natural killer
      cell supernatant accumulated small amounts of lipid after 10 days of natural
      killer cell supernatant treatment. Adipose-derived stem cells treated with
      natural killer cell supernatant showed altered expression of adipogenesis
      associated genes compared with cells maintained in growth media. Adipose-derived
      stem cells maintained in adipogenic media with natural killer cell supernatant
      accumulated less lipid than those cells in adipogenic media alone. CONCLUSIONS:
      The authors demonstrate that, through secreted factors, natural killer cells are
      capable of differentiating adipose-derived stem cells. In cells maintained in
      adipogenic media, treatment with natural killer cell supernatant modulated
      adipogenic potential.

PMID- 26313824
TI  - The Effect of Normovolemic and Hypervolemic Hemodilution on a Microsurgical
      Model: Experimental Study in Rats.
AB  - BACKGROUND: Nowadays, postoperative flap perfusion impairment still occurs in
      free flap surgery; despite several studies on microcirculatory physiology, the
      effect of hemodilution is still extremely controversial. The aim of this study
      was to investigate the impact of acute normovolemic and hypervolemic hemodilution
      on the incidence of flap survival rate in a microsurgical rat model. METHODS:
      Forty female Wistar rats were divided into four groups of 10 rats each: in group
      1, a superficial inferior epigastric artery flap was elevated until femoral
      vessels were isolated, sectioned, and anastomosed without hemodilution; in group
      2, surgery with previous acute normovolemic hemodilution was performed; in group
      3, surgery with previous hypervolemic hemodilution was performed; and group 4,
      was used as a negative control to validate the microsurgical model. Normovolemic
      hemodilution was obtained, with simultaneous removal of an average of 2.25 cc of
      blood and replacement with an equal volume of isotonic sodium chloride 0.9
      percent and hydroxyethyl starch 6 percent. Hypervolemic hemodilution was obtained
      by hemodilution and a 20 percent blood volume expansion. Microangiography of the
      flap and histopathologic analyses were performed. RESULTS: Mean hematocrit values
      after the hemodilution were 26.80 +/- 0.05 percent for group 2 and 28.11 +/- 0.04
      percent for group 3. Skin flap survival and vascularization after 7 days were
      significantly higher in both hemodiluted groups compared with the control group
      (p < 0.05). CONCLUSION: Hemodilution was an effective way of providing better
      microcirculatory blood perfusion, increasing significantly the flap survival rate
      in the authors' microsurgical model.

PMID- 26313825
TI  - A Cadaver Study of the Feasibility of Multidigit Allotransplantation for
      Reconstruction of the Metacarpal Hand.
AB  - BACKGROUND: Amputation of all fingers (metacarpal hand) can be functionally
      equivalent to hand amputation. Multidigit allotransplantation can benefit
      patients who require a full complement of fingers to return to their preinjury
      activities. The authors investigated the feasibility of the transfer of four
      fingers and thumb as a single allograft. METHODS: Four fingers and the thumb were
      harvested from 16 hands as an allograft based on the radial and ulnar arteries.
      Dorsal digital veins were dissected until confluent in the major veins. The
      common digital nerves were divided at the origin. The flexor and extensor tendons
      were transected, respectively, in zones V and VI. The fingers were disarticulated
      at the metacarpophalangeal joint. After harvest, ulnar and radial arteries were
      injected with red and blue India ink, respectively, followed by injection of lead
      gel in the ulnar artery to study the perfusion of the fingers. Digital
      radiographs and computed tomographic scans were obtained. A bilateral mock
      transplantation was performed. RESULTS: The ulnar artery perfused the small,
      ring, long, and ulnar half of the index finger, whereas the radial artery
      vascularized the thumb. The index finger represented a watershed area. The
      presence of contrast in the four fingers, decreasing toward the radial fingers,
      was confirmed by computed tomography. The mock transplantation procedure was
      performed successfully. CONCLUSIONS: Multidigit transplantation is an
      anatomically feasible procedure. Although the ulnar artery can supply the entire
      allograft, the variable anatomy of the palmar arches should be considered and the
      flap based on both ulnar and radial arteries.

PMID- 26313826
TI  - Thirty Years of Prenatal Cleft Diagnosis: What Have We Learned?
AB  - Prenatal ultrasound diagnosis of cleft lip with or without cleft palate has
      received little attention in the plastic surgery literature despite its initial
      description more than 30 years ago. With more families presenting in the prenatal
      period, it is critical for plastic surgeons to understand the techniques in use
      today for prenatal cleft diagnosis as well as their associated limitations.
      Moreover, it is incumbent on surgeons to understand the implications of the
      diagnosis as well as how to appropriately counsel affected families, including
      how to handle questions pertaining to termination. A comprehensive review was
      initiated to educate plastic surgeons with respect to these aims. The following
      points may be inferred: (1) Based on the rates of associated anomalies in low
      risk screened populations, as opposed to the high-risk groups in previous
      reports, prenatally detected clefts do not appear intrinsically different from
      historically described cohorts; (2) in the absence of structural anomalies,
      chromosomal anomalies in prenatally detected cleft patients are rare; (3)
      ultrasound detection rates are highly variable across studies (10 percent to 90
      percent); (4) reporting errors range from 10 percent to 60 percent and largely
      relate to characterization of the secondary palate; (5) accuracy is improving
      with the adoption of newer technologies, including three-dimensional ultrasound;
      and (6) prenatal diagnosis enables counseling and a sense of preparedness for the
      majority of affected families and only rarely results in termination for isolated
      clefts. 

PMID- 26313827
TI  - Restoration of Trigeminal Cutaneous Sensation with Cross-Face Sural Nerve Grafts:
      A Novel Approach to Facial Sensory Rehabilitation.
AB  - Although treating facial palsy is considered debilitating for patients,
      trigeminal nerve palsy and sensory deficits of the face are overlooked components
      of disability. Complete anesthesia leaves patients susceptible to occult injury,
      and facial sensation is an important component of interaction and activities of
      daily living. Sensory reconstruction is well established in the restoration of
      hand sensation; however, only one previous report proposed a surgical strategy
      for sensory nerve reconstruction of the face with use of nerve transfers. Nerve
      transfers, when used alone, have limited application because of their restricted
      arc of rotation in the face; extending their arc by adding nerve grafts greatly
      expands their utility. The following cases demonstrate the early results after V2
      and V3 reconstruction with cross-face nerve grafts in three patients with
      acquired trigeminal nerve palsy. Cross-face nerve grafts using the sural nerve
      permit more proximal reconstruction of the infraorbital and mental nerves, which
      allows reinnervation of their entire cutaneous distribution. All patients
      demonstrated improved sensation in the reconstructed dermatomes, and no patients
      reported donor-site abnormalities. Cross-face nerve grafts result in minimal
      donor-site morbidity and are promising as a surgical strategy to address sensory
      deficits of the face. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

PMID- 26313828
TI  - Hysterectomy with Concurrent Panniculectomy: A Propensity-Matched Analysis of 30
      Day Outcomes.
AB  - BACKGROUND: The goal of this multicenter study was to examine 30-day outcomes
      following combined hysterectomy and panniculectomy compared with hysterectomy
      alone at a national level. METHODS: Female patients who underwent hysterectomy
      with or without concurrent panniculectomy were identified in the 2005 through
      2012 American College of Surgeons National Surgical Quality Improvement Program
      Participant Use Data Files. Propensity scores were used to match patients who
      underwent combined surgery to a sample of similar patients who underwent
      hysterectomy alone. RESULTS: A total of 24,893 patients who underwent
      hysterectomy alone and 174 patients who underwent hysterectomy with concurrent
      panniculectomy were identified. Patients who underwent combined surgery were more
      often obese (body mass index >=30 kg/m2), with diabetes mellitus, and
      cardiovascular/pulmonary comorbidities. Unadjusted outcomes for the total cohort
      showed that patients who underwent both procedures more often experienced venous
      thromboembolism (2.9 percent versus 1.0 percent; p = 0.015) and length of stay
      greater than 3 days (48.3 percent versus 29.2 percent; p < 0.001). In the
      propensity-matched sample, there were no differences shown in the proportion of
      patients who experienced wound complications, surgical-site infections, venous
      thromboembolism, medical complications, or total complications. However, patients
      who underwent both procedures were twice as likely to experience length of stay
      greater than 3 days (OR, 2.06; 95 percent CI, 1.28 to 3.31). CONCLUSIONS:
      Combined hysterectomy and panniculectomy procedures appear to be performed
      infrequently among American College of Surgeons National Surgical Quality
      Improvement Program-participating hospitals. After propensity matching, only
      differences in length of stay were identified. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Therapeutic, III.

PMID- 26313829
TI  - Closed Incision Negative-Pressure Therapy Is Associated with Decreased Surgical
      Site Infections: A Meta-Analysis.
AB  - BACKGROUND: Negative-pressure therapy has recently been used over closed
      incisions to decrease surgical-site occurrences, including infection and
      dehiscence. A meta-analysis was performed to evaluate the effectiveness of closed
      incision negative-pressure therapy in lowering the incidence of surgical-site
      infections compared with standard dressings. METHODS: A literature search was
      conducted to find publications comparing closed incision negative-pressure
      therapy to standard incisional care. A fixed-effects model was used to assess
      between-study and between-incision location subgroup heterogeneity and effect
      size. Funnel plots were used to assess publication bias. RESULTS: The overall
      weighted average rates of surgical-site infection in the closed incision negative
      pressure therapy and control groups were 6.61 percent and 9.36 percent,
      respectively. This reflects a relative reduction in surgical site infection rate
      of 29.4 percent. A decreased likelihood of surgical-site infection was evident in
      the closed incision negative-pressure therapy group compared with the control
      group across all studies, and across all four incision location subgroups. Across
      all studies, odds of surgical-site infections decreased 0.564 (p < 0.00001).
      After excluding groin incision studies because of heterogeneity following
      sensitivity analysis, the odds of surgical-site infection decrease was still
      0.496 (p < 0.00001). In addition, overall rates of dehiscence in closed incision
      negative-pressure therapy and control groups were 5.32 percent and 10.68 percent,
      respectively. CONCLUSIONS: The results of this meta-analysis suggest that closed
      incision negative-pressure therapy is a potentially effective method for reducing
      surgical-site infections. It also appears that closed incision negative-pressure
      therapy may be associated with a decreased incidence of dehiscence, but the
      published data available were too heterogeneous to perform meta-analysis.

PMID- 26313830
TI  - Are Quantitative Measures of Academic Productivity Correlated with Academic Rank
      in Plastic Surgery? A National Study.
AB  - BACKGROUND: The purpose of this study was to investigate the correlation between
      quantitative measures of academic productivity and academic rank among full-time
      academic plastic surgeons. METHODS: Bibliometric indices were computed for all
      full-time academic plastic surgeons in the United States. The primary study
      variable was academic rank. Bibliometric predictors included the Hirsch index, I
      10 index, number of publications, number of citations, and highest number of
      citations for a single publication. Descriptive, bivariate, and correlation
      analyses were computed. Multiple comparisons testing was used to calculate
      adjusted associations for subgroups. For all analyses, a value of p < 0.05 was
      considered significant. RESULTS: The cohort consisted of 607 plastic surgeons
      across 91 Accreditation Council for Graduate Medical Education-approved programs.
      Of them, 4.1 percent were instructors/lecturers, 43.7 percent were assistant
      professors, 22.1 percent were associate professors, 25.7 percent were professors,
      and 4.4 percent were endowed professors. Mean values were as follows: Hirsch
      index, 10.2 +/- 9.0; I-10 index, 17.2 +/- 10.2; total number of publications,
      45.5 +/- 69.4; total number of citations, 725.0 +/- 1448.8; and highest number of
      citations for a single work, 117.8 +/- 262.4. Correlation analyses revealed
      strong associations of the Hirsch index, I-10 index, number of publications, and
      number of citations with academic rank (rs = 0.62 to 0.64; p < 0.001).
      CONCLUSIONS: Academic rank in plastic surgery is strongly correlated with several
      quantitative metrics of research productivity. Although academic promotion is the
      result of success in multiple different areas, bibliometric measures may be
      useful adjuncts for assessment of research productivity.

PMID- 26313831
TI  - Discussion: Are Quantitative Measures of Academic Productivity Correlated with
      Academic Rank in Plastic Surgery? A National Study.

PMID- 26313833
TI  - Lack of Validity of the American College of Surgeons National Surgical Quality
      Improvement Program Database for Alloplastic Immediate Postmastectomy
      Reconstruction.
AB  - BACKGROUND: The American College of Surgeons National Surgical Quality
      Improvement Program is an outcomes-based program with the objective of improving
      quality of surgical care. With its size and validity, the database has been mined
      by both general and plastic surgery clinical researchers to provide information
      for possible risk reduction strategies and patient counseling. However, the 30
      day window of the program's database may be inappropriately brief in
      documentation of complications for some operative procedures. The authors'
      hypothesis was that the database underestimated complications in alloplastic
      reconstruction, particularly prosthesis loss. METHODS: A cohort of 346 patients
      and 511 immediate postmastectomy reconstructions was analyzed for reconstruction
      failure. The inclusion criterion was patients who underwent reconstruction with
      tissue expanders followed by removal because of complications of infection and/or
      exposure. The hiatus between surgery (postmastectomy reconstruction) and loss of
      the tissue expander was recorded. Demographic data and risk factors and
      postoperative complications of mastectomy skin necrosis and seroma were
      tabulated. RESULTS: Fifty-five tissue expanders were explanted in the
      postoperative period secondary to infection and/or exposure. Of the total, 19
      tissue expanders were explanted within 30 days, 36 after the 30-day window (mean,
      62 days; median, 43 days). Approximately 65 percent of the tissue expanders
      destined for eventual loss were still in situ at 30 days. No significant
      difference existed between the two groups, early and late, regarding risk factors
      or postoperative mastectomy skin necrosis and seroma. CONCLUSION: The American
      College of Surgeons National Surgical Quality Improvement Program database
      significantly underestimates the risk of tissue expander loss because of the 30
      day limitation in data accrual. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic,
      III.

PMID- 26313834
TI  - Role of Autologous Fat Transfer to the Superficial Fat Compartments for Perioral
      Rejuvenation.
AB  - BACKGROUND: Autologous fat transfer to the deep compartments of the face has
      proven to be a powerful adjunct to volume restoration during rhytidectomy.
      However, to treat all components of volume deflation in facial aging, the
      perioral superficial compartments must be addressed. Various fillers have been
      used to augment these compartments; however, few studies have assessed the
      efficacy of autologous fat transfer to these areas. This study is the largest
      series to date to assess the utility of autologous fat transfer to the perioral
      superficial compartments. METHODS: A retrospective chart review was conducted on
      an individualized component rhytidectomy database. Patients who underwent
      autologous fat transfer to the perioral superficial fat compartments were
      identified; patients who did not undergo autologous fat transfer served as
      controls. All patients had follow-up images that had been obtained a minimum of 1
      year postoperatively. Three independent observers reviewed preoperative and
      postoperative images using the Modified Fitzpatrick Wrinkle Scale. RESULTS: Sixty
      five consecutive patients underwent rhytidectomy without perioral rejuvenation
      (group A), and 65 patients underwent rhytidectomy with autologous fat transfer to
      the perioral superficial compartments (group B). Group B had a two times more
      significant improvement in perioral aesthetics than group A. CONCLUSIONS: This
      study is the largest review to date demonstrating safety, longevity, and success
      of autologous fat as an ideal filler of the perioral superficial compartments. In
      light of the aesthetic improvements with autologous fat transfer to the perioral
      region, this surgical adjunct should be a fundamental component to achieve global
      facial rejuvenation during rhytidectomy.

PMID- 26313835
TI  - Efficacy and Safety of Botulinum Toxin Type A in the Treatment of Glabellar
      Lines: A Meta-Analysis of Randomized, Placebo-Controlled, Double-Blind Trials.
AB  - BACKGROUND: The uses of botulinum toxin type A for facial aesthetic procedures
      have been reported in recently published studies. The authors systematically
      analyzed the prospective, randomized, controlled trials, which continue to
      expand. New efficacy data and endpoints regarding the safety of botulinum toxin
      type A injection for treating glabellar lines were analyzed. METHODS: The authors
      identified randomized controlled trials of botulinum toxin type A through
      searches of Ovid MEDLINE, PubMed, Elsevier, and the Cochrane Library from January
      of 2002 to November of 2014. The search terms included "botulinum toxin" and
      "glabellar lines." Only randomized, placebo-controlled, double-blind trials that
      used an injection dose of 20 units were included in the analysis. Safety was
      assessed by means of a meta-analysis of the number and frequency of adverse
      events. RESULTS: Seven studies involving 1474 subjects met inclusion criteria and
      qualified for meta-analysis. Overall, the pooled effective rate assessed by
      investigators in botulinum toxin type A treatment groups was significantly higher
      than that in controls (relative risk, 33.54; 95 percent CI, 18.65 to 60.33). The
      effective rate in treatment groups using a new endpoint was also higher than that
      in controls (relative risk, 99.04; 95 percent CI, 14.0 to 700.58). Subgroup
      analysis confirmed that botulinum toxin type A could improve the appearance of
      glabellar lines at rest (relative risk, 5.88; 95 percent CI, 3.49 to 9.91). There
      were no significant differences in the frequency of adverse events between the
      treatment and placebo groups in any of the studies. CONCLUSION: This meta
      analysis shows that a single 20-unit dose of botulinum toxin type A is considered
      remarkably effective and safe for the treatment of glabellar lines. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

PMID- 26313836
TI  - An Experimental Study to Bridge a Nerve Gap with a Decellularized Allogeneic
      Nerve.
AB  - BACKGROUND: The authors evaluated the efficacy of decellularized nerve as a
      scaffold for nerve regeneration. METHODS: Sciatic nerves harvested from Sprague
      Dawley rats were decellularized in combination with sodium dodecyl sulfate and
      Triton X-100, and examined with scanning electron microscopy and
      immunofluorescence staining. A graft into the sciatic nerve in Wistar rats was
      performed with the decellularized Sprague-Dawley rat sciatic nerves [allograft:
      10 mm long (n = 3) for short term and 15 mm long (n = 5) for long term]. As a
      control, a portion of sciatic nerve of Wistar rats was cut, reversed, and
      resutured in situ [autograft: 10 mm long (n = 3) and 15 mm long (n = 5) for
      different terms, respectively]. Samples were harvested 4 weeks postoperatively
      and prepared for immunohistochemistry. Von Frey hair test, static toe spread
      factor measurement, and electrophysiologic and histomorphologic analyses were
      carried out to evaluate nerve recovery 24 weeks postoperatively. RESULTS:
      Scanning electron microscopic images revealed the honeycomb structure, and
      immunohistology showed that the three-dimensional structure of the basal lamina
      column on which cell adhesion molecules are integrated is preserved through the
      decellularization protocols. Limited ED1-positive macrophage invasion was found
      through the decellularized sciatic nerves, suggesting that antigenicity remained
      more or less after this treatment. Nevertheless, NF160-positive axons accompanied
      by S100-positive Schwann cells penetrated through the decellularized sciatic
      nerves. Sciatic nerve function had recovered, and there were no significant
      differences in the electrophysiologic and histomorphologic recovery in the
      groups. CONCLUSION: These results suggest that the decellularized allogeneic
      nerve is a suitable scaffold to bridge a nerve gap.

PMID- 26313838
TI  - Septic Tenosynovitis of the Hand: Factors Predicting Need for Subsequent
      Debridement.
AB  - BACKGROUND: Treatment of septic hand tenosynovitis is complex, and often requires
      multiple debridements and prolonged antibiotic therapy. The authors undertook
      this study to identify factors that might be associated with the need for
      subsequent debridement (after the initial one) because of persistence or
      secondary worsening of infection. METHODS: In this retrospective single-center
      study, the authors included all adult patients who presented to their emergency
      department from 2007 to 2010 with septic tenosynovitis of the hand. RESULTS: The
      authors identified 126 adult patients (55 men; median age, 45 years), nine of
      whom were immunosuppressed. All had community-acquired infection; 34 (27 percent)
      had a subcutaneous abscess and eight (6 percent) were febrile. All underwent at
      least one surgical debridement and had concomitant antibiotic therapy (median, 15
      days; range, 7 to 82 days). At least one additional surgical intervention was
      required in 18 cases (median, 1.13 interventions; range, one to five
      interventions). All but four episodes (97 percent) were cured of infection on the
      first attempt after a median follow-up of 27 months. By multivariate analysis,
      only two factors were significantly associated with the outcome "subsequent
      surgical debridement": abscess (OR, 4.6; 95 percent CI, 1.5 to 14.0) and longer
      duration of antibiotic therapy (OR, 1.2; 95 percent CI, 1.1 to 1.2). CONCLUSION:
      In septic tenosynovitis of the hand, the only presenting factor that was
      statistically predictive of an increased risk of needing a second debridement was
      the presence of a subcutaneous abscess. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Risk, III.

PMID- 26313837
TI  - Heat Shock Protein 90 Inhibitor Decreases Collagen Synthesis of Keloid
      Fibroblasts and Attenuates the Extracellular Matrix on the Keloid Spheroid Model.
AB  - BACKGROUND: The 90-kDa heat-shock protein (heat-shock protein 90) is an abundant
      cytosolic chaperone, and inhibition of heat-shock protein 90 by 17-allylamino-17
      demethoxygeldanamycin (17-AAG) compromises transforming growth factor (TGF)-beta
      mediated transcriptional responses by enhancing TGF-beta receptor I and II
      degradation, thus preventing Smad2/3 activation. In this study, the authors
      evaluated whether heat-shock protein 90 regulates TGF-beta signaling in the
      pathogenesis and treatment of keloids. METHODS: Keloid fibroblasts were treated
      with 17-AAG (10 MUM), and mRNA levels of collagen types I and III were determined
      by real-time reverse- transcriptase polymerase chain reaction. Also, secreted TGF
      beta1 was assessed by enzyme-linked immunosorbent assay. The effect of 17-AAG on
      protein levels of Smad2/3 complex was determined by Western blot analysis. In
      addition, in 17-AAG-treated keloid spheroids, the collagen deposition and
      expression of major extracellular matrix proteins were investigated by means of
      Masson trichrome staining and immunohistochemistry. RESULTS: The authors found
      that heat-shock protein 90 is overexpressed in human keloid tissue compared with
      adjacent normal tissue, and 17-AAG decreased mRNA levels of type I collagen,
      secreted TGF-beta1, and Smad2/3 complex protein expression in keloid fibroblasts.
      Masson trichrome staining revealed that collagen deposition was decreased in 17
      AAG-treated keloid spheroids, and immunohistochemical analysis showed that
      expression of collagen types I and III, elastin, and fibronectin was markedly
      decreased in 17-AAG-treated keloid spheroids. CONCLUSION: These results suggest
      that the antifibrotic action of heat-shock protein 90 inhibitors such as 17-AAG
      may have therapeutic effects on keloids.

PMID- 26313839
TI  - The Supercharge End-to-Side Anterior Interosseous-to-Ulnar Motor Nerve Transfer
      for Restoring Intrinsic Function: Clinical Experience.
AB  - BACKGROUND: The authors reviewed their initial clinical experience with the
      supercharge end-to-side anterior interosseous-to-ulnar motor nerve transfer and
      refined their indications for this technique. METHODS: A retrospective cohort
      study was performed of all patients undergoing the supercharge end-to-side
      procedure from 2009 to 2012. Preoperative and intraoperative data were reviewed.
      Function was evaluated using manual muscle testing; pinch/grip strength; and
      Disabilities of the Arm, Shoulder and Hand questionnaire scores. Differences in
      preoperative and postoperative function were evaluated using paired t tests and
      Wilcoxon signed rank tests. Predictors of poor outcome and changes in outcome
      over time were also analyzed. RESULTS: Fifty-five patients (69 percent men; mean
      age, 50.0 +/- 15.5 years) were included. Diagnoses were varied, but all patients
      demonstrated clinically significant ulnar intrinsic weakness and
      electrodiagnostic evidence of denervation of the first dorsal interosseous
      muscle. Postoperative first dorsal interosseous strength; key pinch strength;
      grip strength; and Disabilities of the Arm, Shoulder and Hand questionnaire
      scores improved significantly from baseline at a mean follow-up of 8.0 +/- 5.7
      months. No patients demonstrated weakness of pronation postoperatively. Absent
      preoperative compound muscle action potentials in the ulnar nerve significantly
      predicted poor intrinsic muscle recovery. The degree of intrinsic recovery
      attributable to the supercharge end-to-side transfer was difficult to determine.
      CONCLUSIONS: The supercharge end-to-side anterior interosseous-to-ulnar nerve
      transfer may be a useful technique for augmenting intrinsic muscle function for
      severe, in-continuity lesions of the ulnar nerve where limited surgical options
      exist. Future research is required to determine the proportion of intrinsic
      recovery attributable to this transfer. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, IV.

PMID- 26313840
TI  - Unilateral Cleft Lip Revision with Conversion to the Modified Inferior Triangle.
AB  - BACKGROUND: Unilateral cleft lip revision may be necessary to address visible
      scars, unequal anatomical boundaries, vermillion inequities, or some combination
      thereof. In the setting of more than one stigma, a complete recreation of the
      defect and repair is necessary. This study anthropometrically evaluates the
      results of cleft lip revision following conversion to the modified inferior
      triangle. METHODS: A retrospective analysis of patients who underwent cleft lip
      revision using the modified inferior triangle was included. Standard preoperative
      and postoperative photographs were obtained and evaluated. Anthropometric points
      were placed and measurements performed. Results were corroborated by two
      independent, blinded reviewers (Pearson correlation test), and compared using the
      paired t test. RESULTS: Twenty-seven patients were included (mean age, 10.89
      years; female, n = 10) over a 35-month period. Intraobserver and interobserver
      ratios were shown to be reliable. Significant differences (p < 0.05) were seen in
      the philtrum column height (PCH), hemilabial length (HL), and hemilabial length'
      (HL') preoperatively. No significant differences (p > 0.05) were noted in the
      PCH, HL, and HL' postoperatively. Significant changes (p < 0.05) between
      DeltaPCH, DeltaHL, and DeltaHL' of cleft side and DeltaPCH, DeltaHL, and DeltaHL'
      of noncleft side were found. Philtral height showed significant changes (p <
      0.05) after conversion to the modified inferior triangle. Significant changes (p
      < 0.05) were found in the philtrum column width and mouth width. CONCLUSION:
      Cleft lip revision is effectively performed using the modified inferior triangle
      repair, improving the lip appearance with improved anthropometric measures.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 26313841
TI  - Complex Abdominal Wall Reconstruction: A Novel Approach to Postoperative Care
      Using Physical Medicine and Rehabilitation.
AB  - BACKGROUND: Abdominal wall defects remain a significant cause of morbidity and
      mortality in the United States. Postoperative rehabilitation programs have been
      used consistently in many surgical subspecialties with exceptional results. Such
      programs have proven to decrease the total time patients require to resume daily
      activities. The authors describe a systematic rehabilitation protocol developed
      with the physical medicine and rehabilitation department that has significantly
      decreased recurrence rates in patients undergoing complex abdominal wall
      reconstruction. METHODS: A retrospective analysis was carried out on patients
      presenting for open repair of an abdominal wall defect performed by a single
      surgeon. Over a 5-year period, there were 275 consecutive patients divided into
      two similar groups: one group consisted of 137 patients that received abdominal
      wall rehabilitation; a second group of 138 patients did not. Patient demographics
      including body mass index, number of hernia defects, number of previous
      repairs/abdominal operations, defect size, operative time, blood loss, and
      postoperative complications including recurrence were collected. RESULTS:
      Patients enrolled in the abdominal wall rehabilitation program were found to have
      fewer recurrences at follow-up, with statistical significance compared with those
      that were not enrolled in the program. CONCLUSIONS: The implementation of the
      abdominal wall rehabilitation program has resulted in a decrease in recurrence
      rates following complex abdominal wall hernia repair and reconstruction. This is
      an innovative system that uses rehabilitation and physical therapy to enhance the
      psychosocial and occupational status of patients by improving recurrence rates.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 26313842
TI  - Practical Management of Metacarpal Fractures.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Understand the indications for metacarpal fixation. 2. Understand the
      rationale for various surgical treatment options, based on high-level evidence
      where available. 3. Describe selected operative techniques and their
      postoperative management. BACKGROUND: Metacarpal fractures are extremely common,
      constituting one in five fractures that present to the emergency department.
      Although many metacarpal fractures can be treated nonoperatively, some require
      surgery. The purpose of this CME article is to present a practical, up-to-date
      guide to the management of these common injuries. METHODS: A review of
      nonoperative management, surgical indications, and selected surgical techniques
      is provided. The authors reviewed the literature related to the treatment of
      metacarpal fractures, and the highest level evidence available to help guide
      decision-making is presented. CONCLUSIONS: Metacarpal fractures can often be
      treated nonoperatively, although some fractures will benefit from surgical
      treatment. Although there is some high-level evidence to guide decision-making,
      there are many clinical scenarios for which there is little high-quality
      applicable research. As a general principle, the treatment option that achieves
      the desired reduction and degree of fixation, allows early motion, and minimizes
      soft-tissue injury should be preferred.

PMID- 26313843
TI  - Gender Disparities in Academic Practice.
AB  - BACKGROUND: In academia, women remain underrepresented. The authors' sought to
      examine differences in faculty position and professional satisfaction among
      academic physicians by gender. METHODS: From 2008 to 2012, academic faculty
      members at a single institution were surveyed (2008, n = 737; 2010, n = 1151; and
      2012, n = 971) regarding current position, choice of position, professional
      satisfaction, and desire for leaving. Logistic regression was performed to
      compare aspects of professional satisfaction by gender. RESULTS: Men more often
      held tenure track positions compared with women (2008, 45 percent versus 20
      percent; 2010, 47 percent versus 20 percent; and 2012, 49 percent versus 20
      percent; p < 0.001). Women were more likely to engage in only clinical activities
      compared with men (2008, 31 percent versus 18 percent; 2010, 28 percent versus 14
      percent; and 2012, 33 percent versus 13 percent; p < 0.001) and less likely to
      participate in research. Women chose tracks to accommodate work-life balance
      [2008, OR, 1.9 (95 percent CI, 1.29 to 2.76); 2010, OR, 2.0 (95 percent CI, 1.38
      to 2.76); and 2012, OR, 2.1 (95 percent CI, 1.40 to 3.00)], rather than the
      opportunity of tenure [2008, OR, 0.4 (95 percent CI, 0.23 to 0.75); 2010, OR, 0.5
      (95 percent CI, 0.35 to 0.85); and 2012, OR, 0.5 (95 percent CI, 0.29 to 0.76)
      compared with men. Men reported higher professional satisfaction compared with
      women (2008, 5.7 versus 5.4, p < 0.009; 2012, 5.3 versus 5.0, p < 0.03). Men were
      more likely to leave because of leadership opportunities (14.4 percent versus 9.2
      percent, p < 0.03) and compensation (14.2 percent versus 9.2 percent, p < 0.03)
      compared with women. CONCLUSIONS: Women report lower levels of professional
      satisfaction in academic practice compared with men. Given the increasing
      pressures of academic practice, efforts to align work-life balance and
      professional goals could potentially improve faculty satisfaction and retention.

PMID- 26313845
TI  - The Operating Room and the Gridiron.

PMID- 26313844
TI  - Reply: Poly Implant Prothese: Two Studies of the Same Topic.

PMID- 26313846
TI  - Asymmetric Pd-Catalyzed Alkene Carboamination Reactions for the Synthesis of 2
      Aminoindane Derivatives.
AB  - A new type of Pd-catalyzed alkene carboamination reaction that provides direct
      access to enantioenriched 2-aminoindanes from 2-allylphenyltriflate derivatives
      and aliphatic amines is described. A catalyst generated in situ from Pd(OAc)2 and
      (S)-tert-butylPHOX provides the functionalized carbocycles in good yield with up
      to >99:1 er. The transformations occur via a key anti-aminopalladation that
      involves intermolecular attack of an amine nucleophile on an arylpalladium alkene
      complex. 

PMID- 26313847
TI  - Supra-nutritional vitamin E supplementation for 28 days before slaughter
      maximises muscle vitamin E concentration in finisher pigs.
AB  - A 4 * 3 factorial experiment (n=8 pigs per treatment combination) was conducted
      with 96 female Landrace * Large White pigs to examine the required level of
      dietary vitamin E and optimum feeding duration before slaughter to maximise
      muscle vitamin E content in the Longissimus thoracis et lumborum (LTL) muscle.
      The respective factors were four dietary levels of vitamin E (supplemented as dl
      alpha-tocopheryl acetate; 35, 300, 500, and 700 IU/kg) and three feeding
      durations (14, 28 and 42 days before slaughter). Vitamin E concentration in the
      LTL was maximised at 6 mg/kg, which was achieved by feeding a 700 IU vitamin E
      diet for 28 days before slaughter (P<0.001). There was no further increase in the
      vitamin E content of the LTL by feeding the high vitamin E diet more than 28 days
      before slaughter.

PMID- 26313848
TI  - Negative life events and depression in adolescents with HIV: a stress and coping
      analysis.
AB  - The prevalence of negative life events (NLE) and daily hassles, and their direct
      and moderated associations with depression, were examined among HIV-infected
      adolescents. Specifically, we examined whether the negative association with
      depression of NLE, daily hassles, and/or passive coping were moderated by social
      support or active coping strategies. Demographic characteristics, depression,
      coping, social support, NLE, and daily hassles were collected at baseline as part
      of the Adolescent Impact intervention via face-to-face and computer-assisted
      interviews. Of 166 HIV-infected adolescents, 53% were female, 72.9% black, 59.6%
      with perinatally acquired HIV (PIY), the most commonly reported NLE were death in
      family (81%), violence exposure (68%), school relocation (67%), and
      hospitalization (61%); and for daily hassles "not having enough money (65%)".
      Behaviorally infected youth (BIY--acquired HIV later in life) were significantly
      more likely to experience extensive (14-21) lifetime NLE (38.8% vs. 16.3%, p <
      .012) than PIY. In multiple stepwise regression analysis, the model accounting
      for the greatest variability in depression scores (32%) included (in order of
      entry): daily hassles, low social support, behaviorally acquired HIV, minority
      sexual orientation, and passive coping. A significant passive coping-by-social
      support interaction revealed that the association between passive coping and
      depression was exacerbated when social support was low. Social support moderated
      the effect of NLE, such that NLE were associated with greater depression when
      social support was low, although the effect did not remain statistically
      significant when main effects of other variables were accounted for. Daily
      hassles, poor coping, and limited social support can adversely affect the
      psychological well-being of HIV-infected adolescents, particularly sexual
      minority youth with behaviorally acquired HIV. Multimodal interventions that
      enhance social support and teach adaptive coping skills may help youth cope with
      environmental stresses and improve mental health outcomes.

PMID- 26313849
TI  - The Reaction Mechanism of Bovine Lens Leucine Aminopeptidase.
AB  - We present a quantum mechanical/molecular mechanical (QM/MM) study using the AM1
      Hamiltonian and a flexible MM part on the mode of action of the bovine lens
      leucine aminopeptidase (blLAP), a cytosolic exopeptidase that catalyzes the
      cleavage of the N-terminal amide bond of peptides. The reaction mechanism of this
      ubiquitous enzyme has not yet been clarified completely, although some
      suggestions based on crystallographic data have been made. One path of the
      several possibilities investigated was found to be clearly the most favorable and
      in good agreement with experimental results. Besides the elucidation of the
      functional roles of active-site residues, an estimation of the environment
      effects is given. 

PMID- 26313850
TI  - Advances in microfluidic platforms for analyzing and regulating human pluripotent
      stem cells.
AB  - Microfluidic devices employ submillimeter length scale control of flow to achieve
      high-resolution spatial and temporal control over the microenvironment, providing
      powerful tools to elucidate mechanisms of human pluripotent stem cell (hPSC)
      regulation and to elicit desired hPSC fates. In addition, microfluidics allow
      control of paracrine and juxtracrine signaling, thereby enabling fabrication of
      microphysiological systems comprised of multiple cell types organized into organs
      on-a-chip. Microfluidic cell culture systems can also be integrated with
      actuators and sensors, permitting construction of high-density arrays of cell
      based biosensors for screening applications. This review describes recent
      advances in using microfluidics to understand mechanisms by which the
      microenvironment regulates hPSC fates and applications of microfluidics to
      realize the potential of hPSCs for in vitro modeling and screening applications. 

PMID- 26313851
TI  - First-Principles Theoretical Studies and Nanocalorimetry Experiments on Solid
      State Alloying of Zr-B.
AB  - The thermodynamics and kinetics of the solid-state alloying of Zr-B, underlying a
      variety of synthesis processes of the ultrahigh-temperature ceramic ZrB2, are
      widely unknown. We investigate the energetics, diffusion kinetics, and structural
      evolution of this system using first-principles computational methods. We
      identify the diffusion pathways in the interpenetrating network of interstitial
      sites for a single B atom and demonstrate a dominant rate-controlling step from
      the octahedral to the crowdion site that is distinct from the conventional
      mechanism of octahedral-tetrahedral transition in hexagonal close-packed
      structures. In the intermediate compounds ZrBx, 0 < x <= 2, the diffusivity of B
      is highly dependent on the composition while reaching a minimum for ZrB. The
      activation barrier of diffusion in ZrB2 is in good agreement with nanocalorimetry
      measurements performed on Zr/B reactive nanolaminates. 

PMID- 26313853
TI  - Nystagmus in an Emaciated Infant.

PMID- 26313852
TI  - Treatment of inflammatory myopathy: emerging therapies and therapeutic targets.
AB  - Despite the lack of placebo-controlled trials, glucocorticoids are considered the
      mainstay of initial treatment for idiopathic inflammatory myopathy and myositis
      associated interstitial lung disease. Glucocorticoid-sparing agents are often
      given concomitantly with other immunosuppressive agents, particularly in patients
      with moderate or severe disease. First-line conventional immunosuppressive drugs
      include either methotrexate or azathioprine, and when they fail, more aggressive
      therapy includes mycophenolate mofetil, tacrolimus or cyclosporine, intravenous
      immunoglobulin, rituximab, or cyclophosphamide, used alone or in various
      combinations. Further investigations are required to assess the role of more
      novel therapies in the treatment of myositis and myositis-associated interstitial
      lung disease. 

PMID- 26313854
TI  - Stem-ing mTOR: p53 maintains the male germline.

PMID- 26313855
TI  - Ethics of care in medical tourism: Informal caregivers' narratives of
      responsibility, vulnerability and mutuality.
AB  - This study examines the experiences of informal caregivers in medical tourism
      through an ethics of care lens. We conducted semi-structured interviews with 20
      Canadians who had accompanied their friends or family members abroad for surgery,
      asking questions that dealt with their experiences prior to, during and after
      travel. Thematic analysis revealed three themes central to an ethics of care:
      responsibility, vulnerability and mutuality. Ethics of care theorists have
      highlighted how care has been historically devalued. We posit that medical
      tourism reproduces dominant narratives about care in a novel care landscape.
      Informal care goes unaccounted for by the industry, as it occurs in largely
      private spaces at a geographic distance from the home countries of medical
      tourists. 

PMID- 26313856
TI  - Photobiostimulation effect on diabetic wound at different power density of near
      infrared laser.
AB  - The photobiostimulation effects of near infrared 808 nm diode laser irradiance on
      diabetic wound were investigated. 120 rats were induced with diabetes by
      streptozotocin injection. Full thickness punch wounds of 6mm diameter were
      created on the dorsal part of the rats. All rats were randomly distributed into
      four groups; one group served as control group, whereas three groups were
      stimulated daily with unchanged energy density dose of 5 J/cm(2) with different
      power density, which were 0.1 W/cm(2), 0.2 W/cm(2) and 0.3 W/cm(2) with different
      exposure duration of 50s, 25s and 17s, respectively. Ten rats from each group
      were sacrificed on day 3, 6 and 9, respectively. Skin tissues were removed for
      histological purpose. The contraction of wound was found optimized after exposure
      with 0.1 W/cm(2). Based on the histological evidence, laser therapy has shown
      able to promote wound repair through enhanced epithelialization and collagen
      fiber synthesis. Generally, irradiated groups were advanced in terms of healing
      than non-irradiated group.

PMID- 26313857
TI  - Optical characterization of core-shell quantum dots embedded in synthetic saliva:
      Temporal dynamics.
AB  - The present work reports the spectroscopic and thermo-optical properties of
      CdSe/ZnS and CdSe/CdS core-shell quantum dots (QDs) embedded in synthetic saliva.
      Spectroscopy studies were performed applying nonfunctionalized CdSe/ZnS QDs (3.4,
      3.9 and 5.1 nm cores) and hydroxyl group-functionalized ultrasmall CdSe/CdS core
      shell quantum dots (1.6 nm core) suspended in artificial saliva at different
      potential of hydrogen (pH) values. Saliva was chosen because it is important in a
      variety of functions such as protecting teeth through the buffering capacity of
      the formed biofilm, hydration, and dental remineralization. Thermo-optical
      characterizations using the thermal lens (TL) technique were performed in QD
      biofluids for different QD sizes and pH values (3.9-8.3) of the synthetic oral
      fluids. Transient TL measurements were applied to determine the fluorescence
      quantum efficiency (eta) in QD-biomaterial systems. High eta value was obtained
      for ultrasmall CdSe/CdS QDs. Fluorescence spectral measurements of the
      biomaterials support the TL results. In addition, for nonfunctionalized (3.4 and
      5.1 nm) and hydroxyl group-functionalized QDs, the temporal behavior of the
      fluorescence spectra was accomplished about approximately 1200 h at two different
      biofluid pH values (3.9 and 8.3). The temporal fluorescence intensity result is
      dependent on the pH of the saliva in which the QDs were embedded, QD
      functionalization and QD sizes. The time for an approximately 50% decrease in the
      peak intensity fluorescence of CdSe/ZnS QDs (3.4 nm core) and ultrasmall CdSe/CdS
      QDs is respectively 25 h and 312 h at pH 3.9 and 48 h and 360 h at pH 8.3.

PMID- 26313858
TI  - Equilibrium sampling of polychlorinated biphenyls in River Elbe sediments-
      Linking bioaccumulation in fish to sediment contamination.
AB  - Equilibrium sampling can be applied to measure freely dissolved concentrations
      (cfree) of hydrophobic organic chemicals (HOCs) that are considered effective
      concentrations for diffusive uptake and partitioning. It can also yield
      concentrations in lipids at thermodynamic equilibrium with the sediment
      (clip?sed) by multiplying concentrations in the equilibrium sampling polymer with
      lipid to polymer partition coefficients. We have applied silicone coated glass
      jars for equilibrium sampling of seven 'indicator' polychlorinated biphenyls
      (PCBs) in sediment samples from ten locations along the River Elbe to measure
      cfree of PCBs and their clip?sed. For three sites, we then related clip?sed to
      lipid-normalized PCB concentrations (cbio,lip) that were determined independently
      by the German Environmental Specimen Bank in common bream, a fish species living
      in close contact with the sediment: (1) In all cases, cbio,lip were below
      clip?sed, (2) there was proportionality between the two parameters with high R(2)
      values (0.92-1.00) and (3) the slopes of the linear regressions were very similar
      between the three stations (0.297; 0.327; 0.390). These results confirm the close
      link between PCB bioaccumulation and the thermodynamic potential of sediment
      associated HOCs for partitioning into lipids. This novel approach gives clearer
      and more consistent results compared to conventional approaches that are based on
      total concentrations in sediment and biota-sediment accumulation factors. We
      propose to apply equilibrium sampling for determining bioavailability and
      bioaccumulation potential of HOCs, since this technique can provide a
      thermodynamic basis for the risk assessment and management of contaminated
      sediments. 

PMID- 26313859
TI  - In reply: Treatment of cachexia: An overview of recent developments.

PMID- 26313860
TI  - Catheter Ablation Resolves Ventricular Arrhythmias in a Patient with Sarcoidosis.

PMID- 26313861
TI  - Galectin-3 is a marker of myocardial and vascular fibrosis in Kawasaki disease
      patients with giant aneurysms.
AB  - BACKGROUNDS: Galectin-3 (Gal-3) is a multifunctional matricellular protein
      associated with heart failure and cardiovascular events. Gal-3 is required for
      transforming growth factor-beta pathway-mediated myofibroblast activation that is
      a key process in coronary artery aneurysm formation in Kawasaki Disease (KD).
      Autopsies from young adults late after KD onset (AKD) have demonstrated bridging
      fibrosis throughout the myocardium and arteries. In this study, we postulated
      that Gal-3 may participate in the pathogenesis of myocardial and vascular
      fibrosis and the remodeling of coronary artery aneurysms following acute KD.
      METHODS AND RESULTS: We measured plasma Gal-3 levels in 63 pediatric KD (PKD) and
      81 AKD subjects. AKD subjects with giant aneurysms had significantly higher Gal-3
      levels compared to the other adult groups (all p<0.05). All PKD groups had
      significantly higher Gal-3 levels than pediatric healthy controls (HC) (all
      p<0.05). Histological and immunohistochemical staining was performed on tissues
      from 10 KD autopsies and one explanted heart. Gal-3 positive staining was
      detected associated with acute inflammation and in spindle-shaped cells in the
      myocardium and arterial wall in KD subjects with giant aneurysms. CONCLUSIONS:
      AKD subjects with giant aneurysms and PKD subjects had significantly higher
      plasma Gal-3 levels than HC and Gal-3 expression was increased in the myocardium
      of KD subjects who died with either acute inflammation or marked myocardial
      fibrosis. Gal-3 may be a clinically useful biomarker that identifies a subset of
      KD patients at highest risk of myocardial and vascular fibrosis, and may be an
      attractive therapeutic target to prevent myocardial dysfunction in this subset.

PMID- 26313862
TI  - Interventricular septum aneurysm: Two differently managed cases and association
      with bicuspid aortic valve.

PMID- 26313863
TI  - Rho-associated kinase inhibitors promote the cardiac differentiation of embryonic
      and induced pluripotent stem cells.
AB  - BACKGROUND: Rho-associated kinase (ROCK) plays an important role in maintaining
      embryonic stem (ES) cell pluripotency. To determine whether ROCK is involved in
      ES cell differentiation into cardiac and hematopoietic lineages, we evaluated the
      effect of ROCK inhibitors, Y-27632 and fasudil on murine ES and induced
      pluripotent stem (iPS) cell differentiation. METHODS: Gene expression levels were
      determined by real-time PCR, Western blot analysis and immunofluorescent confocal
      microscopy. Cell transplantation of induced differentiated cells were assessed in
      vivo in a mouse model (three groups, n=8/group) of acute myocardial infarction
      (MI). The cell engraftment was examined by immunohistochemical staining and the
      outcome was analyzed by echocardiography. RESULTS: Cells were cultured in
      hematopoietic differentiation medium in the presence or absence of ROCK inhibitor
      and colony formation as well as markers of ES, hematopoietic stem cells (HSC) and
      cells of cardiac lineages were analyzed. ROCK inhibition resulted in a drastic
      change in colony morphology accompanied by loss of hematopoietic markers (GATA-1,
      CD41 and beta-Major) and expressed markers of cardiac lineages (GATA-4, Isl-1,
      Tbx-5, Tbx-20, MLC-2a, MLC-2v, alpha-MHC, cTnI and cTnT) in murine ES and iPS
      cells. Fasudil-induced cardiac progenitor (Mesp-1 expressing) cells were infused
      into a murine MI model. They engrafted into the peri-infarct and infarct regions
      and preserved left ventricular function. CONCLUSIONS: These findings provide new
      insights into the signaling required for ES cell differentiation into
      hematopoietic as well as cardiac lineages and suggest that ROCK inhibitors are
      useful in directing iPS cell differentiation into cardiac progenitor cells for
      cell therapy of cardiovascular diseases.

PMID- 26313864
TI  - Double cardiac diverticula after pericardectomy.

PMID- 26313865
TI  - Impact Factor: Vagaries, inconsistencies and illogicalities; should it be
      abandoned?

PMID- 26313866
TI  - How to research the mechanisms of non-pharmacological cardiac interventions.
AB  - OBJECTIVE: To discuss research into the mechanisms of non-pharmacological
      interventions for cardiac populations. METHODS: Overview of past research and
      theory. RESULTS: Non-pharmacological interventions for cardiac patients
      (including: cardiac rehabilitation, heart failure disease management programs and
      psychosocial interventions) have never been so common or diverse, but also have
      never been subject to so much scrutiny and skepticism. Better understanding of
      outcomes of these interventions is an urgent global priority. Mechanisms are the
      "underlying entities, processes, or structures which operate in particular
      contexts to generate outcomes of interest." PRACTICE: Research into the
      mechanisms of non-pharmacological interventions offers useful and robust
      knowledge of how and why cardiac interventions work that can be vital to
      explaining outcomes from interventions and inconsistencies in results.
      CONCLUSIONS: Research into intervention mechanisms can inform the design and
      optimization of interventions. IMPLICATIONS: We recommend that future research
      into the mechanisms of non-pharmacological interventions for cardiac population
      1) view effectiveness as 'somewhat' patterned, 2) conceptualize mechanisms
      adequately, 3) assume they are hidden, 4) examine how context affects mechanisms,
      and 6) address what works for whom, when, and why.

PMID- 26313867
TI  - Expression of Hedgehog signaling molecules in human atherosclerotic lesions: An
      autopsy study.

PMID- 26313868
TI  - Bland-White-Garland syndrome diagnosed by computed tomography.

PMID- 26313869
TI  - Periodontal disease and risk of coronary heart disease: An updated meta-analysis
      of prospective cohort studies.

PMID- 26313870
TI  - Impact of race and obesity on arterial endothelial dysfunction associated with
      sleep apnea: Results from the Heart SCORE study.

PMID- 26313871
TI  - Treatment and outcome of coronary artery perforations using a dual guiding
      catheter technique.
AB  - OBJECTIVES: To evaluate the success rate and outcome of coronary artery
      perforation treatment using a dual guiding catheter technique. BACKGROUND:
      Coronary artery perforation is a rare but severe complication during percutaneous
      coronary intervention (PCI) with high mortality. The use of a second guiding
      catheter is a helpful technique to minimize hemorrhage through the perforation
      during interventional repair. METHODS: We screened all patients between March
      2004 and December 2014 who underwent PCI in our department for the occurrence of
      peri-interventional coronary perforation that was treated using a dual catheter
      technique. Patient and lesion characteristics as well as outcome were determined.
      RESULTS: We identified 8 patients who experienced coronary artery perforations
      (Ellis grade III) during coronary intervention and were treated using a dual
      guiding catheter approach. The procedure was technically successful (placement of
      covered stent and sealing of perforation) in 6 patients. Pericardiocentesis was
      required in 3 patients (38%). Total mortality was 12% (n=1). No coronary or
      peripheral vascular access complication occurred due to the use of a second
      guiding catheter. CONCLUSIONS: We suggest that the dual guiding catheter
      technique is a useful and alternative approach to treat severe Ellis grade III
      coronary artery perforations that occur in the context of percutaneous coronary
      interventions.

PMID- 26313872
TI  - Percutaneous pulmonary valve implantation: A systematic review of clinical
      outcomes.

PMID- 26313873
TI  - Prognostic significance of low QRS voltage on the admission electrocardiogram in
      acute coronary syndromes.

PMID- 26313874
TI  - Divergent Synthesis of alpha,gamma-Disubstituted gamma-Butyrolactones through
      Diastereoselective Bromolactonization with Alkali Metal Bromide: Asymmetric Total
      Synthesis of (+)-Dubiusamine C.
AB  - A divergent synthesis of alpha-substituted bromomethyl gamma-lactones was
      developed, which involves the diastereoselective bromolactonization of alpha
      substituted 4-pentenoic acids and 4-pentenamides via umpolung of bromide by use
      of alkali metal bromide and Oxone (potassium peroxymonosulfate mixture,
      2KHSO5.KHSO4.K2SO4) to obtain mainly cis-products from alpha-substituted 4
      pentenoic acids and trans-products from alpha-substituted 4-pentenamides, and it
      was found that the bromonium species generated from KBr and Oxone had higher
      activity than N-bromosuccinimide. Furthermore, the asymmetric total synthesis of
      (+)-dubiusamine C, which was isolated as a minor diastereomer from Pandanus
      dubius, was accomplished for the first time through the cis-selective
      bromolactonization of (S)-alpha-methyl-4-pentenoic acid in nine linear steps and
      36% overall yield. 

PMID- 26313875
TI  - Talented football players' development of achievement motives, volitional
      components, and self-referential cognitions: A longitudinal study.
AB  - Adolescence is regarded as a key developmental phase in the course of talented
      football players' careers. The present study focuses on early adolescent players'
      development of achievement motives, volitional components, and self-referential
      cognitions. Based on the multidimensional and dynamic nature of talent, the
      development of multifaceted personality characteristics is an important issue in
      the context of sports talent research. According to previous findings in
      psychology, personality characteristics' development is defined by both stability
      and change, and the current study analyses four different types: differential
      stability (I), mean-level change (II), individual-level change (III), and
      structural stability (IV). The sample consists of 151 male players in the talent
      development programme of the German Football Association. Psychological
      diagnostics of the personality characteristics are implemented across
      longitudinal sections over a time period of three seasons, from the U12 to U14
      age classes. The results reveal that the personality characteristics show (I)
      moderate test-retest correlations over one-year intervals (.43 <= rtt <= .62),
      and lower coefficients for a two-year period (.26 <= rtt <= .53). (II) Most of
      the personality characteristics' mean values differ significantly across the age
      classes with small effect sizes (.01 <= [Formula: see text] <= .03). (III) Only
      minor individual-level changes in the football players' development are found.
      (IV) The personality characteristics' associations within a two-factor structure
      do not stay invariant over time. From the results of the present study,
      conclusions are drawn regarding the talent identification and development
      process.

PMID- 26313876
TI  - A palladium-catalyzed enantioselective hydroesterification of alkenylphenols with
      phenyl formate. A facile approach to optically active dihydrocoumarins.
AB  - An effective palladium-catalyzed enantioselective hydroesterification of
      alkenylphenols with phenyl formate as a CO source is described. A variety of
      optically active dihydrocoumarins can be obtained in generally high yields with
      up to 91% ee. 

PMID- 26313877
TI  - Chloride promoted room temperature preparation of silver nanoparticles on two
      dimensional tungsten oxide nanoarchitectures for the catalytic oxidation of
      tertiary N-compounds to N-oxides.
AB  - A halide ion promoted two dimensional silver tungsten-based nanomaterial was
      synthesized by a facile one-pot synthesis protocol at room temperature. The 2D
      morphology features high activity and selectivity for the oxidation of a wide
      range of tertiary N-compounds to their corresponding N-oxides. The morphology of
      Ag/WO3 materials can be varied by changing the synthesis parameters. The unique
      2D plate like morphology of tungsten oxide increases adsorption sites of the
      support, leading to less sintering and higher dispersion of silver nanoparticles,
      resulting in significantly enhanced activity for the reaction. The influence of
      reaction parameters such as temperature, substrate to oxidant molar ratio,
      reaction time, etc. was investigated in detail. The catalyst was characterized by
      XRD, XPS, ICP-AES, TGA, FT-IR, UV-vis, Raman, SEM, TEM and STEM. Raman studies
      further provide mechanistic insight which proves that the formation of peroxo
      tungsten species is responsible for the N-oxidation reaction. High stability and
      recyclability of the 2D Ag/WO3 nanoplates are also observed under the
      investigated conditions. 

PMID- 26313878
TI  - Electron Probe Microanalysis of REE in Eudialyte Group Minerals: Challenges and
      Solutions.
AB  - Accurate quantification of the chemical composition of eudialyte group minerals
      (EGM) with the electron probe microanalyzer is complicated by both mineralogical
      and X-ray-specific challenges. These include structural and chemical variability,
      mutual interferences of X-ray lines, in particular of the rare earth elements,
      diffusive volatility of light anions and cations, and instability of EGM under
      the electron beam. A novel analytical approach has been developed to overcome
      these analytical challenges. The effect of diffusive volatility and beam damage
      is shown to be minimal when a square of 20*20 um is scanned with a beam diameter
      of 6 um at the fastest possible speed, while measuring elements critical to
      electron beam exposure early in the measurement sequence. Appropriate reference
      materials are selected for calibration considering their volatile content and
      composition, and supplementary offline overlap correction is performed using
      individual calibration factors. Preliminary results indicate good agreement with
      data from laser ablation inductively coupled plasma mass spectrometry
      demonstrating that a quantitative mineral chemical analysis of EGM by electron
      probe microanalysis is possible once all the parameters mentioned above are
      accounted for. 

PMID- 26313879
TI  - [Breast ultrasonographic features and internal mammary artery hemodynamic indexes
      during normal pregnancy].
AB  - PURPOSE: To evaluate breast ultrasonographic features and hemodynamic indexes of
      the internal mammary arteries in normal pregnant women, and their correlation
      with the gestational periods. METHODS: Observational and cross-sectional,
      epidemiological, study, conducted between August 2013 and February 2015, with 93
      women divided into three groups: first trimester, second trimester and third
      trimester. The dependent variables were thickness of the skin, of subcutaneous
      tissue, fibroglandular tissue, and retrommamary adipose tissue, the diameter of
      the ducts, as well as the pulsatility and resistance indexes of the internal
      mammary arteries. Independent variables were the three periods of gestation.
      Repeated measures ANOVA with the multiple comparison Tukey test and a test of
      contrasts were used for statistical analysis. The Levene test was used to test
      the homogeneity of variances between periods of gestation. Student's t-test was
      used to evaluate the difference between nulliparous and non -nulliparous women,
      and Pearson's correlation coefficient was used for correlation analysis between
      the two breasts. The level of significance was set at 5%. RESULTS: Mean age was
      26.6+/-4.6 years, with no significant difference among groups. Breast location
      (right/left) and gestational period had no significant effect on the thickness of
      the skin, of subcutaneous tissue and adipose retromammary tissue. However, the
      thickness of fibroglandular tissue and the diameter of the ducts showed a
      significant difference according to gestational period (p<0.001), i.e., from the
      first to the second and to the third trimesters. Doppler flowmetry of the
      internal mammary arteries showed a difference between breasts and between
      gestational periods, i.e., the measurements of the right breast were greater than
      those of the left, and these values decreased throughout pregnancy (p<0.001).
      CONCLUSION: The average thickness of fibroglandular tissue and the diameter of
      the ducts showed significant differences from the first to the second and to the
      third trimesters, with no differences being observed between the two breasts. The
      pulsatility and resistance indexes of the internal mammary arteries decreased
      progressively throughout pregnancy.

PMID- 26313880
TI  - [Lactobacillus rhamnosus may change the virulence of Candida albicans].
AB  - PURPOSE: To investigate the influence of Lactobacillus rhamnosus in the
      expression of virulence factors of Candida albicans in vitro. METHODS: A
      suspension of L. rhamnosus was initially grown in MRS agar. The other day,
      Sabouraud dextrose agar was added on the growth of lactobacilli and C. albicans
      was seeded for 24, 48 and 72 hours. Candida strains were then isolated for
      investigation of the ability of biofilm formation, by means of cultivation into
      96 wells plaque, and reading the optical densities and counting colony forming
      units per mL. Also the ability of germ tube formation was investigated, after
      incubation in horse serum and counting of 200 cells. The results were compared to
      Candida strains grown in the absence of L. rhamnosus, using Student's t test for
      statistical analysis. RESULTS: there was a significant reduction in the growth of
      C. albicans in the presence of lactobacilli after 24, 48 or 72 hours. Significant
      reduction was also observed in germ tube formation after interaction for 48 or 72
      hours. For biofilm formation, no statistically significant difference was
      observed between the Candida strains grown in the presence or absence of
      lactobacilli. CONCLUSION: The results suggest that L. rhamnosus is able to
      influence significantly the growth and expression of virulence factors of C.
      albicans in vitro, and may interfere with pathogenicity of these micro-organisms.

PMID- 26313882
TI  - [Relation between nucleated red blood cell count in umbilical cord and the
      obstetric and neonatal outcomes in small for gestational age fetuses and with
      normal Doppler velocimetry of umbilical artery].
AB  - PURPOSE: To analyze the obstetrical and neonatal outcomes of pregnancies with
      small for gestation age fetuses after 35 weeks based on umbilical cord nucleated
      red blood cells count (NRBC). METHODS: NRBC per 100 white blood cells were
      analyzed in 61 pregnancies with small for gestation age fetuses and normal
      Doppler findings for the umbilical artery. The pregnancies were assigned to 2
      groups: NRBC>=10 (study group, n=18) and NRBC<10 (control group, n=43).
      Obstetrical and neonatal outcomes were compared between these groups. The chi(2)
      test or Student's t-test was applied for statistical analysis. The level of
      significance was set at 5%. RESULTS: The mean +/- standard deviation for NRBC per
      100 white blood cells was 25.0 +/- 13.5 for the study group and 3.9 +/- 2.2 for
      the control group. The NRBC>=10 group and NRBC<10 group were not significantly
      different in relation to maternal age (24.0 versus 26.0), primiparity (55.8
      versus 50%), comorbidities (39.5 versus 55.6%) and gestational age at birth (37.4
      versus 37.0 weeks). The NRBC>=10 group showed higher rate of caesarean delivery
      (83.3 versus 48.8%, p=0.02), fetal distress (60 versus 0%, p<0.001) and pH<7.20
      (42.9 versus 11.8%, p<0.001). The birth weight and percentile of birth weight for
      gestational age were significantly lower on NRBC>=10 group (2,013 versus 2,309 g;
      p<0.001 and 3.8 versus 5.1; p=0.004; respectively). There was no case described
      of 5th minute Apgar score below 7. CONCLUSION: An NRBC higher than 10 per 100
      white blood cells in umbilical cord was able to identify higher risk for
      caesarean delivery, fetal distress and acidosis on birth in small for gestational
      age fetuses with normal Doppler findings.

PMID- 26313883
TI  - [Influence of hormonal contraceptives on indices of zinc homeostasis and bone
      remodeling in young adult women].
AB  - PURPOSE: To investigate the influence of the use of oral hormonal contraceptive
      agents (OCA) on the biochemical indices related to metabolic zinc utilization and
      distribution, and to bone turnover in young adult women. METHODS: Cross-sectional
      study. Blood and urine samples from non-users (-OCA; control; n=69) and users of
      hormonal contraceptives for at least 3 months (+OCA; n=62) were collected under
      controlled conditions. Indices of zinc homeostasis and of bone turnover were
      analyzed in serum or plasma (total, albumin-bound and alpha2-macroglobulin-bound
      zinc, albumin and total and bone alkaline phosphatase activity), in erythrocytes
      (zinc and metallothionein) and in urine (zinc, calcium and hydroxyproline). The
      habitual zinc and calcium intakes were evaluated by a food frequency
      questionnaire. RESULTS: Dietary zinc intake was similar in both groups and on
      average above recommended values, whereas calcium intake was similarly sub
      adequate in +OCA and -OCA. Compared to controls, +OCA had lower concentrations of
      total and alpha2-macroglobulin-bound zinc (11 and 28.5%, respectively, p<0.001),
      serum albumin (13%, p<0.01), total and bone-specific alkaline phosphatase
      activity (13 and 18%, respectively, p<0.05), erythrocyte metallothionein (13%,
      p<0.01), and, urinary zinc (34%, p<0.05). CONCLUSIONS: OCA use decreases serum
      zinc, alters zinc distribution in major serum fractions with possible effects on
      tissue uptake, enhances zinc retention in the body and decreases bone turnover.
      Prolonged OCA use may lead to lower peak bone mass and/or to impaired bone mass
      maintenance in young women, particularly in those with marginal calcium intake.
      The observed OCA effects were more evident in women younger than 25 years and in
      nulliparous women, deserving special attention in future studies.

PMID- 26313884
TI  - Efficient control of coulomb enhanced second harmonic generation from excitonic
      transitions in quantum dot ensembles.
AB  - In this work, the second harmonic generation from excitonic transitions in
      semiconductor quantum dots is computationally studied. By integrating a density
      matrix treatment with a partial configuration interaction approach, we obtain the
      second order susceptibility as a function of externally applied electric and
      magnetic fields for highly confined neutral and charged excitons. Our results
      show an enhancement in the nonlinear response with respect to analogous optical
      processes based on intraband transitions, and predict their efficient tunability
      by taking advantage of the interplay between Coulomb effects and field-driven
      wave function manipulation. 

PMID- 26313887
TI  - Production of quasi-2D graphene nanosheets through the solvent exfoliation of
      pitch-based carbon fiber.
AB  - Stable dispersion of quasi-2D graphene sheets with a concentration up to 1.27 mg
      mL(-1) was prepared by sonication-assisted solvent exfoliation of pitch-based
      carbon fiber in N-methyl pyrrolidone with the mass yield of 2.32%. Prepared quasi
      2D graphene sheets have multi-layered 2D plate-like morphology with rich
      inclusions of graphitic carbons, a low number of structural defects, and high
      dispersion stability in aprotic polar solvents, and facilitate the utilization of
      quasi-2D graphene sheets prepared from pitch-based carbon fiber for various
      electronic and structural applications. Thin films of quasi-2D graphene sheets
      prepared by vacuum filtration of the dispersion of quasi-2D graphene sheets
      demonstrated electrical conductivity up to 1.14 * 10(4) Omega/? even without
      thermal treatment, which shows that pitch-based carbon fiber might be useful as
      the source of graphene-related nanomaterials. Because pitch-based carbon fiber
      could be prepared from petroleum pitch, a very cheap structural material for the
      pavement of asphalt roads, our approach might be promising for the mass
      production of quasi-2D graphene nanomaterials.

PMID- 26313885
TI  - Streaking artifact reduction for quantitative susceptibility mapping of sources
      with large dynamic range.
AB  - Quantitative susceptibility mapping (QSM) is a novel MRI technique for the
      measurement of tissue magnetic susceptibility in three dimensions. Although
      numerous algorithms have been developed to solve this ill-posed inverse problem,
      the estimation of susceptibility maps with a wide range of values is still
      problematic. In cases such as large veins, contrast agent uptake and intracranial
      hemorrhages, extreme susceptibility values in focal areas cause severe streaking
      artifacts. To enable the reduction of these artifacts, whilst preserving subtle
      susceptibility contrast, a two-level QSM reconstruction algorithm (streaking
      artifact reduction for QSM, STAR-QSM) was developed in this study by tuning a
      regularization parameter to automatically reconstruct both large and small
      susceptibility values. Compared with current state-of-the-art QSM methods, such
      as the improved sparse linear equation and least-squares (iLSQR) algorithm, STAR
      QSM significantly reduced the streaking artifacts, whilst preserving the sharp
      boundaries for blood vessels of mouse brains in vivo and fine anatomical details
      of high-resolution mouse brains ex vivo. Brain image data from patients with
      cerebral hematoma and multiple sclerosis further illustrated the superiority of
      this method in reducing streaking artifacts caused by large susceptibility
      sources, whilst maintaining sharp anatomical details. STAR-QSM is implemented in
      STI Suite, a comprehensive shareware for susceptibility imaging and
      quantification.

PMID- 26313888
TI  - A Qualitative Study into Egyptian Patients' Satisfaction with Physiotherapy
      Management of Low Back Pain.
AB  - BACKGROUND AND PURPOSE: There is strong evidence suggesting that patient
      satisfaction may improve therapy outcomes independent of the treatment given.
      Thus the aim of this study is to explore Egyptian patients' expectations and
      satisfaction with physical therapy management of low back pain. METHODS: A
      qualitative study design involving two focus groups and 10 semi-structured
      interviews; all discussions were audio recorded, transcribed verbatim and
      analysed using a Framework analysis approach. RESULTS: The five final themes were
      about outcome of the treatment episode, the therapist characteristics, their
      ability to provide patient education, the service provision and involvement in
      the decision-making process. CONCLUSION: The therapeutic encounter between
      patients and therapists in an episode of back care is complex and reflects the
      multidimensional nature of patient satisfaction. Participants had several
      criteria according to which they evaluated the quality of care and were able to
      determine when these criteria were met or not during physiotherapy. Copyright (c)
      2015 John Wiley & Sons, Ltd.

PMID- 26313889
TI  - Early Diagnosis of Diabetes through the Eye.
AB  - Diabetes mellitus is a metabolic disorder characterized by high blood sugar
      levels which give rise to complications in the eye, kidneys and the brain.
      Diabetes triggers the development of ocular diseases like diabetic retinopathy
      and cataracts which are the leading cause of blindness around the world. The most
      common method for the diagnosis of diabetes involves measuring the blood sugar
      levels in the body. One major disadvantage of this method is the fluctuating
      blood sugar levels which contribute to false negative results. This leads to
      delay in treatment, eventually causing permanent damage to the organs. Therefore,
      diagnosis of diabetes at an early stage is very crucial. One biomarker for
      diabetes related diseases is the formation of Advanced Glycation End-products
      (AGEs) that result from the Maillard reaction of proteins with glucose. alpha
      crystallin in the ocular lens is a small heat shock protein with no protein
      turnover and hence acts as a record for post-translational modifications
      especially glycation which forms AGEs. We have used steady state and time
      resolved fluorescence measurements to study the spectroscopic changes in alpha
      crystallin with increase in time of glycation and the intact lenses from diabetic
      and nondiabetic donors. Overall, this study was focused on developing a
      noninvasive diagnostic tool for early detection of diabetes mellitus. 

PMID- 26313890
TI  - A Dispersion-Dominated Chromogenic Strategy for Colorimetric Sensing of
      Glutathione at the Nanomolar Level Using Gold Nanoparticles.
AB  - A dispersion-dominated chromogenic strategy for glutathione sensing is developed.
      Glutathione prevents the aggregation of arginine-modified gold nanoparticles via
      mercury-thiol interaction, which allows for glutathione sensing at the nanomolar
      level (10.9 * 10(-9) m) with facile operation and naked-eye readout. 

PMID- 26313891
TI  - Lewis Acid Catalyzed Formal Intramolecular [3 + 3] Cross-Cycloaddition of
      Cyclopropane 1,1-Diesters for Construction of Benzobicyclo[2.2.2]octane
      Skeletons.
AB  - A novel Lewis acid catalyzed formal intramolecular [3 + 3] cross-cycloaddition
      (IMCC) of cyclopropane 1,1-diesters has been successfully developed. This
      supplies an efficient and conceptually new strategy for construction of bridged
      bicyclo[2.2.2]octane skeletons. This [3 + 3]IMCC could be run up to gram scale
      and from easily prepared starting materials. This [3 + 3]IMCC, together with our
      previously reported [3 + 2]IMCC strategy, can afford either the
      bicyclo[2.2.2]octane or bicyclo[3.2.1]octane skeletons from the similar starting
      materials by regulating the substituents on vinyl group. 

PMID- 26313892
TI  - Hydrolyzed Methylhesperidin Induces Antioxidant Enzyme Expression via the Nrf2
      ARE Pathway in Normal Human Epidermal Keratinocytes.
AB  - Methylhesperidin (MHES) is a mixture of methylated derivatives of the citrus
      flavonoid hesperidin and is used as a food or pharmaceutical additive. Dietary
      MHES could be hydrolyzed by gut microflora to give aglycons. Therefore, we
      prepared hydrolyzed methylhesperidin (h-MHES) and assessed its pharmacological
      activity in human epidermal keratinocytes. h-MHES promoted nuclear factor
      erythroid 2-related factor 2 (Nrf2) nuclear translocation and the expression of
      cytoprotective genes (e.g., heme oxygenase-1 (HO-1) and glutamate cysteine ligase
      catalytic subunit (GCLC)). h-MHES also increased intracellular glutathione levels
      and reduced UVB-induced reactive oxygen species. Moreover, h-MHES increased
      phosphorylation of p38 mitogen-activated protein kinase (MAPK), and a p38 MAPK
      inhibitor significantly attenuated h-MHES-induced HO-1 and GCLC expression.
      Furthermore, when we purified the components of h-MHES, we identified two methoxy
      chalcones as novel Nrf2 activators. Our study demonstrates that h-MHES can induce
      cytoprotective gene expression and reduce oxidative stress via the Nrf2-ARE
      pathway in keratinocytes, suggesting that MHES may contribute to the suppression
      of UVB-induced skin damage in vivo. 

PMID- 26313893
TI  - Sessile serrated adenoma/polyp with cytological dysplasia diagnosed accurately by
      magnifying chromoendoscopy.

PMID- 26313894
TI  - Mechanism of action of the tuberculosis and Crohn disease risk factor IRGM in
      autophagy.
AB  - Polymorphisms in the IRGM gene, associated with Crohn disease (CD) and
      tuberculosis, are among the earliest identified examples documenting the role of
      autophagy in human disease. Functional studies have shown that IRGM protects
      against these diseases by modulating autophagy, yet the exact molecular mechanism
      of IRGM's activity has remained unknown. We have recently elucidated IRGM's
      mechanism of action. IRGM functions as a platform for assembling, stabilizing,
      and activating the core autophagic machinery, while at the same time physically
      coupling it to conventional innate immunity receptors. Exposure to microbial
      products or bacterial invasion increases IRGM expression, which leads to
      stabilization of AMPK. Specific protein-protein interactions and post
      translational modifications such as ubiquitination of IRGM, lead to a co-assembly
      with IRGM of the key autophagy regulators ULK1 and BECN1 in their activated
      forms. IRGM physically interacts with 2 other CD risk factors, ATG16L1 and NOD2,
      placing these 3 principal players in CD within the same molecular complex. This
      explains how polymorphisms altering expression or function of any of the 3
      factors individually can affect the same process-autophagy. Furthermore, IRGM's
      interaction with NOD2, and additional pattern recognition receptors such as NOD1,
      RIG-I, and select TLRs, transduces microbial signals to the core autophagy
      apparatus. This work solves the long-standing enigma of how IRGM controls
      autophagy. 

PMID- 26313895
TI  - Initial Experience of a Patient Navigation Model for Head and Neck Cancer.
AB  - IMPORTANCE: Specific temporal goals for treatment of head and neck cancer (HNC)
      are common in Europe but not in the United States. We implemented a patient
      centric navigation model with an aspirational goal that all patients will receive
      treatment recommendations within 2 weeks of presentation as a means to improve
      outcomes in our patients with HNC. OBJECTIVE: To assess the temporal impact of
      using an aspirational goal in a patient-centric navigation system on the time
      from presentation to formulation of treatment planning for patients with HNC.
      DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of 100 consecutive
      patients treated for squamous cell carcinoma of the head and neck at a tertiary
      referral center between 2011 and 2014. Patients were assessed to determine the
      efficiency of a patient-centric navigational model in delivering cancer treatment
      recommendations. This model was designed with an aspirational goal of providing
      treatment recommendations within a 2-week period. EXPOSURE: Starting in 2011,
      patient-centric navigation model including the assignment of a nurse who acts as
      a patient navigator. MAIN OUTCOMES AND MEASURES: The time interval between
      presentation to clinic and definitive treatment recommendations, as well as
      factors associated with delay. RESULTS: Of the 93 patients who met inclusion
      requirements, most were white (81 [87%]) males (74 [80%]) with a mean (SD) age of
      63.4 (10.8) years insured by Medicare or Medicaid (64 [69%]). Forty-seven (51%)
      received treatment recommendations within the 2-week period, with median and mode
      values of 15 and 14 days, respectively. The mean (SD) interval was 18.8 (18.6)
      days. Outliers included 2 patients with synchronous lung nodules (72 and 85 days)
      and 2 patients with psychosocial barriers (107 and 86 days). There were no
      significant differences seen for the mean (SD) time interval with respect to
      patient race (blacks, 17.6 [15.7] vs whites, 22.5 [30.0]; P = .20), sex (males,
      18.3 [18.1] vs females, 20.4 [19.7]; P = .13), insurance status (insured, 16.3
      [10.2] vs uninsured, 19.8 [21.0]; P = .24), and stage at presentation (stage I,
      14.4 [17.0] vs stage II, 11.0 [5.3] vs stage III, 14.7 [8.6] vs stage IV, 21.2
      [20.2]; P = .40). CONCLUSIONS AND RELEVANCE: The goal of treatment
      recommendations for HNC within 2 weeks was shown to be reasonable and attainable.
      Further research should address the delays encountered by patients with
      psychosocial barriers and those with synchronous lung nodules.

PMID- 26313896
TI  - Induction of thermogenesis in brown and beige adipose tissues: molecular markers,
      mild cold exposure and novel therapies.
AB  - PURPOSE OF REVIEW: The purpose of this short review paper is to summarize recent
      developments in the understanding of the activation, growth and function of brown
      adipose tissue (BAT). RECENT FINDINGS: Transcriptional markers for increased BAT
      activity and differentiation of white adipocytes to 'beige' or 'brite' adipocytes
      include amongst others peroxisome proliferator-activated receptor gamma, cytosine
      enhancer-binding protein, positive regulatory domain 16 and bone morphogenetic
      proteins. These markers induce uncoupling protein 1 expression in brown and
      'beige' or 'brite' adipocytes which allows energy from macronutrients to be
      expended as heat. Acute and repeated mild cold exposures of 17-19  degrees C in
      adult humans increase BAT volume and activity and this is a novel method for
      increasing their energy expenditure. Emerging evidence suggests that irisin and
      melatonin hormones may be involved in BAT activation. Additionally, brown
      adipocyte stem cell therapy transplantation is a means to stimulate this
      increased thermogenesis from brown and 'beige' or 'brite' adipocytes. SUMMARY:
      Markers for increased BAT activation and for white adipocyte differentiation into
      beige/brite adipocytes have been identified, and these lead to an uncoupling
      protein 1-mediated increase in metabolic rate. Mild cold exposure and brown
      adipocyte stem cell transplantation are two potential strategies for inducing
      activation and growth of BAT for the treatment of human obesity.

PMID- 26313898
TI  - Obesity medications: what does the future look like?
AB  - PURPOSE OF REVIEW: Lifestyle modification remains the mainstay of treatment for
      obesity despite the lack of substantial long-term efficacy. For many who do not
      respond to lifestyle therapy and are not candidates for weight loss surgery,
      pharmacotherapy is a viable treatment option. Advances in understanding
      mechanisms of appetite control, nutrient sensing, and energy expenditure have not
      only helped shape current drug development but have also changed the way in which
      antiobesity medications are prescribed. Current antiobesity medications and
      pharmacological strategies will be reviewed. RECENT FINDINGS: Two new antiobesity
      drugs - naltrexone/bupropion (Contrave) and liraglutide (Saxenda) - were approved
      by the US Food and Drug Administration in 2014 and join four other approved
      obesity medications, including phentermine/topiramate XR (Qsymia) and lorcaserin
      (Belviq), to form the largest number of medications available for the treatment
      of obesity. In addition, investigational drugs, like belnoranib, show promise in
      early clinical trials, brightening the outlook on drug development. SUMMARY: To
      combat the complex physiological system of energy regulation and the known
      variation of treatment response, combinatory therapies for obesity, including
      pharmacotherapy, are needed. Now six US Food and Drug Administration-approved
      antiobesity medications, including two combination medications, will allow
      providers to tailor obesity treatment in combination with lifestyle modification
      for a great number of individuals with obesity.

PMID- 26313897
TI  - Leptin applications in 2015: what have we learned about leptin and obesity?
AB  - PURPOSE OF REVIEW: To summarize previous and current advancements for leptin
      therapeutics, we described how leptin may be useful in leptin deficient states
      such as lipodystrophy, for which leptin was recently approved, and how it may be
      useful in the future for typical obesity. RECENT FINDINGS: The discovery of
      leptin in 1994 built the foundation for understanding the pathophysiology and
      treatment of obesity. Leptin therapy reverses morbid obesity related to
      congenital leptin deficiency and appears to possibly treat lipodystrophy, a
      finding which has led to the approval of leptin for the treatment of
      lipodystrophy in the USA and Japan. Typical obesity, on the other hand, is
      characterized by hyperleptinemia and leptin tolerance. Thus, leptin
      administration has proven ineffective for inducing weight loss on its own but
      could possibly be useful in combination with other therapies or for weight loss
      maintenance. SUMMARY: Leptin is not able to treat typical obesity; however, it is
      effective for reversing leptin deficiency-induced obesity and is possibly useful
      in lipodystrophy. New mechanisms and pathways involved in leptin resistance are
      continuously discovered, whereas the development of new techniques and drug
      combinations which may improve leptin's efficacy and safety regenerate the hope
      for its use as an effective treatment for typical obesity.

PMID- 26313899
TI  - Pendrin and anoctamin as mediators of apical iodide efflux in thyroid cells.
AB  - PURPOSE OF REVIEW: Thyroid hormones are essential for normal development, growth,
      and metabolism. Their synthesis occurs in thyroid follicles and requires an
      adequate iodide supply and a sequence of regulated biochemical steps. The uptake
      of iodide into thyrocytes is well characterized, but its efflux at the apical
      membrane is poorly understood. This review discusses potential mechanisms
      underlying iodide efflux with emphasis on recent developments and controversies.
      RECENT FINDINGS: The functional characterization of pendrin (PDS/SLC26A4), a
      multifunctional anion exchanger, suggested that it could be involved in mediating
      iodide efflux. This is supported by the phenotype of patients with Pendred
      syndrome (deafness, goiter, partial iodide organification defect), which is
      caused by biallelic mutations in the SLC26A4 gene, as well as functional studies.
      However, apical iodide efflux is also possible in the absence of pendrin,
      implicating the presence of at least another channel. Recently, Anoctamin 1
      (TMEM16A), a calcium-activated anion channel has been identified at the apical
      membrane of thyrocytes and functional studies suggest that it may play a
      predominant role in mediating iodide efflux. SUMMARY: Anoctamin and pendrin are
      two plausible candidates as mediators of apical iodide efflux. Their relative
      affinity for iodide and their exact physiological role await, however, further
      characterization.

PMID- 26313900
TI  - Anaplastic thyroid cancer.
AB  - PURPOSE OF REVIEW: Anaplastic thyroid cancer (ATC) is a rare malignancy of the
      thyroid with a high mortality rate. Conventional therapy has not been effective.
      Several biological agents are being investigated. The purpose of the review is to
      highlight the current standards for treatment and review new targets for treating
      ATC. RECENT FINDINGS: Retrospective studies have led to formulation of guidelines
      for management, including those by the American Thyroid Association. An expansion
      in the understanding of the genetic mutations has led to several newer biological
      agents being tested to treat ATC. Aurora kinase inhibitors, PPAR gamma agonists,
      and vascular targeting agents are some of the latest therapeutic agents that have
      shown promise and could become standard of therapy with further supporting
      research. SUMMARY: Further well coordinated preclinical and clinical research is
      needed to support the emerging treatments for ATC.

PMID- 26313901
TI  - Selenium and the thyroid.
AB  - PURPOSE OF REVIEW: This article provides an update on the role of the essential
      trace element selenium and its interaction with the other trace elements iodine
      and iron that together contribute to adequate thyroid hormone status. Synthesis,
      secretion, metabolism and action of thyroid hormone in target tissues depend on a
      balanced nutritional availability or supplementation of these elements. Selenium
      status is altered in benign and malignant thyroid diseases and various selenium
      compounds have been used to prevent or treat widespread diseases such as goiter,
      autoimmune thyroid disease or thyroid cancer. RECENT FINDINGS: Several studies,
      most with still too low numbers of cases, indicate that selenium administration
      in both autoimmune thyroiditis (Hashimoto thyroiditis) and mild Graves' disease
      improves clinical scores and well-being of patients and reduces thyroperoxidase
      antibody titers. However, published results are still conflicting depending on
      basal selenium status, dose, time and form of selenium used for intervention.
      Evidence for sex-specific selenium action, lack of beneficial effects in
      pregnancy and contribution of genetic polymorphisms (selenoprotein S) has been
      presented. SUMMARY: Adequate nutritional supply of selenium that saturates
      expression of circulating selenoprotein P, together with optimal iodine and iron
      intake, is required for a healthy and functional thyroid during development,
      adolescence, adulthood and aging.

PMID- 26313902
TI  - Congenital hypothyroidism: recent advances.
AB  - PURPOSE OF REVIEW: This review summarizes significant recent advances in the
      epidemiology, pathophysiology, and treatment of congenital hypothyroidism. RECENT
      FINDINGS: The apparent incidence of congenital hypothyroidism has more than
      doubled in recent years because of several factors, including more inclusive
      diagnostic criteria, shifting demographics, and increasing survival of preterm
      infants. The greatest increase has occurred in mildly affected patients, many of
      whom have a eutopic thyroid gland. Congenital hypothyroidism may be transient or
      persistent, but the natural history cannot be predicted by severity at diagnosis.
      In premature infants, who are especially vulnerable to hypothyroidism, the rise
      in thyroid-stimulating hormone may be delayed and therefore detected only by
      routine follow-up screening. Recent studies of defects in thyroid hormone
      synthesis have focused on the role of mutations in the dual oxidase system and of
      a novel apical iodide transporter, anoctamin 1. Finally, emerging data suggest
      that exposure to excess thyroid hormone may be as harmful as hypothyroidism to
      long-term cognitive development. SUMMARY: Although newborn screening has
      virtually eradicated mental retardation due to congenital hypothyroidism in parts
      of the world, new information continues to accumulate and new questions to arise
      about the diagnosis, physiology, and optimal management of this disorder.

PMID- 26313904
TI  - Shedding of Infectious Borna Disease Virus-1 in Living Bicolored White-Toothed
      Shrews.
AB  - BACKGROUND: Many RNA viruses arise from animal reservoirs, namely bats, rodents
      and insectivores but mechanisms of virus maintenance and transmission still need
      to be addressed. The bicolored white-toothed shrew (Crocidura leucodon) has
      recently been identified as reservoir of the neurotropic Borna disease virus 1
      (BoDV-1). PRINCIPAL FINDINGS: Six out of eleven wild living bicoloured white
      toothed shrews were trapped and revealed to be naturally infected with BoDV-1.
      All shrews were monitored in captivity in a long-term study over a time period up
      to 600 days that differed between the individual shrews. Interestingly, all six
      animals showed an asymptomatic course of infection despite virus shedding via
      various routes indicating a highly adapted host-pathogen interaction. Infectious
      virus and viral RNA were demonstrated in saliva, urine, skin swabs, lacrimal
      fluid and faeces, both during the first 8 weeks of the investigation period and
      for long time shedding after more than 250 days in captivity. CONCLUSIONS: The
      various ways of shedding ensure successful virus maintenance in the reservoir
      population but also transmission to accidental hosts such as horses and sheep.
      Naturally BoDV-1-infected living shrews serve as excellent tool to unravel host
      and pathogen factors responsible for persistent viral co-existence in reservoir
      species while maintaining their physiological integrity despite high viral load
      in many organ systems.

PMID- 26313905
TI  - Effects of macrophage-dependent peroxisome proliferator-activated receptor gamma
      signalling on adhesion formation after abdominal surgery in an experimental
      model.
AB  - BACKGROUND: The pathophysiology of adhesion formation after abdominal and pelvic
      surgery is still largely unknown. The aim of the study was to investigate the
      role of macrophage polarization and the effect of peroxisome proliferator
      activated receptor (PPAR) gamma stimulation on adhesion formation in an animal
      model. METHODS: Peritoneal adhesion formation was induced by the creation of
      ischaemic buttons within the peritoneal wall and the formation of a colonic
      anastomosis in wild-type, interleukin (IL) 10-deficient (IL-10(-/-) ), IL-4
      deficient (IL-4(-/-) ) and CD11b-Cre/PPARgamma(fl) (/fl) mice. Adhesions were
      assessed at regular intervals, and cell preparations were isolated from ischaemic
      buttons and normal peritoneum. These samples were analysed for macrophage
      differentiation and its markers, and expression of cytokines by quantitative PCR,
      fluorescence microscopy, arginase activity and pathological examination. Some
      animals underwent pioglitazone (PPAR-gamma agonist) or vehicle treatment to
      inhibit adhesion formation. Anastomotic healing was evaluated by bursting
      pressure measurement and collagen gene expression. RESULTS: Macrophage M2 marker
      expression and arginase activity were raised in buttons without adhesions
      compared with buttons with adhesions. IL-4(-/-) and IL-10(-/-) mice were not
      affected, whereas CD11b-Cre/PPARgamma(fl) (/fl) mice showed decreased arginase
      activity and increased adhesion formation. Perioperative pioglitazone treatment
      increased arginase activity and decreased adhesion formation in wild-type but not
      CD11b-Cre/PPARgamma(fl) (/fl) mice. Pioglitazone had no effect on anastomotic
      healing. CONCLUSION: Endogenous macrophage-specific PPAR-gamma signalling
      affected arginase activity and macrophage polarization, and counter-regulated
      peritoneal adhesion manifestation. Pharmacological PPAR-gamma agonism induced a
      shift towards macrophage M2 polarization and ameliorated adhesion formation in a
      macrophage-dependent manner. Surgical relevance Postoperative adhesion formation
      is frequently seen after abdominal surgery and occurs in response to peritoneal
      trauma. The pathogenesis is still unknown but includes an imbalance in
      fibrinolysis, collagen production and inflammatory mechanisms. Little is known
      about the role of macrophages during adhesion formation. In an experimental
      model, macrophage M2 marker expression was associated with reduced peritoneal
      adhesion formation and involved PPAR-gamma-mediated arginase activity. Macrophage
      specific PPAR-gamma deficiency resulted in reduced arginase activity and
      aggravated adhesion formation. Pioglitazone, a PPAR-gamma agonist, induced M2
      polarization and reduced postoperative adhesion formation without compromising
      anastomotic healing in mice. Pioglitazone ameliorated postoperative adhesion
      formation without compromising intestinal wound healing. Therefore, perioperative
      PPAR-gamma agonism might be a promising strategy for prevention of adhesion
      formation after abdominal surgery.

PMID- 26313906
TI  - Type I Interferons Function as Autocrine and Paracrine Factors to Induce
      Autotaxin in Response to TLR Activation.
AB  - Lysophosphatidic acid (LPA) is an important phospholipid mediator in inflammation
      and immunity. However, the mechanism of LPA regulation during inflammatory
      response is largely unknown. Autotaxin (ATX) is the key enzyme to produce
      extracellular LPA from lysophosphatidylcholine (LPC). In this study, we found
      that ATX was induced in monocytic THP-1 cells by TLR4 ligand lipopolysaccharide
      (LPS), TLR9 ligand CpG oligonucleotide, and TLR3 ligand poly(I:C), respectively.
      The ATX induction by TLR ligand was abolished by the neutralizing antibody
      against IFN-beta or the knockdown of IFNAR1, indicating that type I IFN autocrine
      loop is responsible for the ATX induction upon TLR activation. Both IFN-beta and
      IFN-alpha were able to induce ATX expression via the JAK-STAT and PI3K-AKT
      pathways but with different time-dependent manners. The ATX induction by IFN-beta
      was dramatically enhanced by IFN-gamma, which had no significant effect on ATX
      expression alone, suggesting a synergy effect between type I and type II IFNs in
      ATX induction. Extracellular LPA levels were significantly increased when THP-1
      cells were treated with IFN-alpha/beta or TLR ligands. In addition, the type I
      IFN-mediated ATX induction was identified in human monocyte-derived dendritic
      cells (moDCs) stimulated with LPS or poly(I:C), and IFN-alpha/beta could induce
      ATX expression in human peripheral blood mononuclear cells (PBMCs) and monocytes
      isolated form blood samples. These results suggest that, in response to TLR
      activation, ATX is induced through a type I INF autocrine-paracrine loop to
      enhance LPA generation. 

PMID- 26313908
TI  - Improving Health-Related Quality of Life among People Living with HIV: Results
      from an Impact Evaluation of a Food Assistance Program in Uganda.
AB  - INTRODUCTION: Widespread food insecurity in Africa continues to compromise an
      effective response to the AIDS epidemic. Health-related quality of life (HRQoL)
      is a comprehensive indicator of physical, mental, and social well-being that is
      associated with food insecurity and increasingly used to assess the well-being of
      people living with HIV/AIDS (PLHIV). We examined the impact of a food assistance
      intervention, previously shown to have reduced household food insecurity and
      improved nutritional status, on HRQoL of PLHIV. METHODS: We capitalized on an
      existing intervention targeting antiretroviral therapy (ART)- naive PLHIV in
      Uganda, and conducted a prospective impact evaluation including a treatment and a
      comparison group. Data analyzed included 640 participants from two districts (318
      in the intervention district) interviewed in both clinic and household settings
      at baseline and again approximately one year later. The main outcomes considered
      were physical and mental health dimensions of HRQoL, and other outcomes included
      self- and healthcare provider-reported symptoms. We utilized difference-in
      difference propensity score matching methodologies to infer causality and examine
      program impacts. RESULTS: Over 12 months, food assistance significantly increased
      physical health scores (PHS) by 2.85 (P < .01) or approximately 0.35 SD, and
      reduced substantially the number of self- and healthcare provider-reported HIV
      related symptoms by 3.83 and 2.68, respectively (P < .01). There was no
      significant impact, however, on mental health scores (MHS). CONCLUSIONS: This
      study demonstrates the potential importance for HRQoL of including food
      assistance programming as part of the standard of care for PLHIV in areas of
      widespread food insecurity.

PMID- 26313907
TI  - Candida albicans Inhibits Pseudomonas aeruginosa Virulence through Suppression of
      Pyochelin and Pyoverdine Biosynthesis.
AB  - Bacterial-fungal interactions have important physiologic and medical
      ramifications, but the mechanisms of these interactions are poorly understood.
      The gut is host to trillions of microorganisms, and bacterial-fungal interactions
      are likely to be important. Using a neutropenic mouse model of microbial
      gastrointestinal colonization and dissemination, we show that the fungus Candida
      albicans inhibits the virulence of the bacterium Pseudomonas aeruginosa by
      inhibiting P. aeruginosa pyochelin and pyoverdine gene expression, which plays a
      critical role in iron acquisition and virulence. Accordingly, deletion of both P.
      aeruginosa pyochelin and pyoverdine genes attenuates P. aeruginosa virulence.
      Heat-killed C. albicans has no effect on P. aeruginosa, whereas C. albicans
      secreted proteins directly suppress P. aeruginosa pyoverdine and pyochelin
      expression and inhibit P. aeruginosa virulence in mice. Interestingly,
      suppression or deletion of pyochelin and pyoverdine genes has no effect on P.
      aeruginosa's ability to colonize the GI tract but does decrease P. aeruginosa's
      cytotoxic effect on cultured colonocytes. Finally, oral iron supplementation
      restores P. aeruginosa virulence in P. aeruginosa and C. albicans colonized mice.
      Together, our findings provide insight into how a bacterial-fungal interaction
      can modulate bacterial virulence in the intestine. Previously described bacterial
      fungal antagonistic interactions have focused on growth inhibition or
      colonization inhibition/modulation, yet here we describe a novel observation of
      fungal-inhibition of bacterial effectors critical for virulence but not important
      for colonization. These findings validate the use of a mammalian model system to
      explore the complexities of polymicrobial, polykingdom infections in order to
      identify new therapeutic targets for preventing microbial disease. 

PMID- 26313909
TI  - High Affinity Binders to EphA2 Isolated from Abdurin Scaffold Libraries;
      Characterization, Binding and Tumor Targeting.
AB  - Abdurins are a novel antibody-like scaffold derived from the engineering of a
      single isolated CH2 domain of human IgG. Previous studies established the
      prolonged serum half-life of Abdurins, the result of a retained FcRn binding
      motif. Here we present data on the construction of large, diverse, phage-display
      and cell-free DNA display libraries and the isolation of high affinity binders to
      the cancer target, membrane-bound ephrin receptor tyrosine kinase class A2
      (EphA2). Antigen binding regions were created by designing combinatorial
      libraries into the structural loops and Abdurins were selected using phage
      display methods. Initial binders were reformatted into new maturation libraries
      and low nanomolar binders were isolated using cell-free DNA display, CIS display.
      Further characterization confirmed binding of the Abdurins to both human and
      murine EphA2 proteins and exclusively to cell lines that expressed EphA2,
      followed by rapid internalization. Two different EphA2 binders were labeled with
      64Cu, using a bifunctional MeCOSar chelator, and administered to mice bearing
      tumors from transplanted human prostate cancer cells, followed by PET/CT imaging.
      The anti-EphA2 Abdurins localized in the tumors as early as 4 hours after
      injection and continued to accumulate up to 48 hours when the imaging was
      completed. These data demonstrate the ability to isolate high affinity binders
      from the engineered Abdurin scaffold, which retain a long serum half-life, and
      specifically target tumors in a xenograft model. 

PMID- 26313910
TI  - Visceral adiposity is associated with an increased risk of functional dyspepsia.
AB  - BACKGROUND: The relationship between visceral adiposity and the incidence of
      functional dyspepsia (FD) has not yet been studied. The purpose of the present
      study is to evaluate the association between visceral adiposity and the risk of
      FD. METHODS: This is a case-control study that compares the abdominal adipose
      tissue area between subjects with FD and control subjects without FD, who
      underwent abdomen computerized tomography (CT) for health examinations in a
      tertiary center. Retrospectively, a telephone survey was conducted to diagnose FD
      using the Rome III criteria. We measured various indices of obesity including
      body mass index (BMI), waist circumference (WC), visceral adipose tissue (VAT)
      area, subcutaneous adipose tissue (SAT) area and the VAT/SAT ratio in order to
      evaluate the association between FD and abdominal adiposity. KEY RESULTS: A total
      of 363 subjects were included in the present study. FD was diagnosed in 90
      subjects (24.8%). In the univariate analysis, WC, VAT area, TAT area, VAT/SAT
      ratio, and the presence of erosive esophagitis were significantly higher in the
      FD group than in the non-FD group. In the multivariate analysis, a higher VAT
      area (odds ratio (OR), 3.76; 95% confidence interval (CI), 1.24-11.40; highest
      quartile vs lowest quartile, p = 0.019) and VAT/SAT ratio (OR, 2.35; 95% CI, 1.27
      4.32; highest quartile vs lowest quartile, p = 0.006) were independently
      associated with a risk of FD. CONCLUSION AND INFERENCES: Visceral adiposity as
      measured by the VAT area and VAT/SAT ratio is associated with an increased risk
      of FD.

PMID- 26313912
TI  - Activation of RARalpha induces autophagy in SKBR3 breast cancer cells and
      depletion of key autophagy genes enhances ATRA toxicity.
AB  - All-trans retinoic acid (ATRA), a pan-retinoic acid receptor (RAR) agonist, is,
      along with other retinoids, a promising therapeutic agent for the treatment of a
      variety of solid tumors. On the one hand, preclinical studies have shown
      promising anticancer effects of ATRA in breast cancer; on the other hand,
      resistances occurred. Autophagy is a cellular recycling process that allows the
      degradation of bulk cellular contents. Tumor cells may take advantage of
      autophagy to cope with stress caused by anticancer drugs. We therefore wondered
      if autophagy is activated by ATRA in mammary tumor cells and if modulation of
      autophagy might be a potential novel treatment strategy. Indeed, ATRA induces
      autophagic flux in ATRA-sensitive but not in ATRA-resistant human breast cancer
      cells. Moreover, using different RAR agonists as well as RARalpha-knockdown
      breast cancer cells, we demonstrate that autophagy is dependent on RARalpha
      activation. Interestingly, inhibition of autophagy in breast cancer cells by
      either genetic or pharmacological approaches resulted in significantly increased
      apoptosis under ATRA treatment and attenuated epithelial differentiation. In
      summary, our findings demonstrate that ATRA-induced autophagy is mediated by
      RARalpha in breast cancer cells. Furthermore, inhibition of autophagy results in
      enhanced apoptosis. This points to a potential novel treatment strategy for a
      selected group of breast cancer patients where ATRA and autophagy inhibitors are
      applied simultaneously. 

PMID- 26313911
TI  - alpha-Solanine induces ROS-mediated autophagy through activation of endoplasmic
      reticulum stress and inhibition of Akt/mTOR pathway.
AB  - alpha-Solanine is a glycoalkaloid found in species of the nightshade family
      including potato. It was primarily reported to have toxic effects in humans.
      However, there is a growing body of literature demonstrating in vitro and in vivo
      anticancer activity of alpha-solanine. Most of these studies have shown
      activation of apoptosis as the underlying mechanism in antitumor activity of
      alpha-solanine. In this study, we report alpha-solanine as a potential inducer of
      autophagy, which may act synergistically or in parallel with apoptosis to exert
      its cytotoxic effect. Induction of autophagy was demonstrated by several assays
      including electron microscopy, immunoblotting of autophagy markers and
      immunofluorescence for LC3 (microtubule-associated protein 1 (MAP1) light chain
      3) puncta. alpha-Solanine-induced autophagic flux was demonstrated by
      additionally enhanced--turnover of LC3-II and--accumulation of LC3-specific
      puncta after co-incubation of cells with either of the autophagolysosome
      inhibitors--chloroquine and--bafilomycin A1. We also demonstrated alpha-solanine
      induced oxidative damage in regulating autophagy where pre-incubation of cells
      with reactive oxygen species (ROS) scavenger resulted in suppression of CM
      H2DCFDA (5 (and 6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate acetyl
      ester) fluorescence as well as decrease in LC3-II turnover. alpha-Solanine
      treatment caused an increase in the expression of endoplasmic reticulum (ER)
      stress proteins (BiP, activating transcription factor 6 (ATF6), X-box-binding
      protein 1, PERK, inositol-requiring transmembrane kinase/endonuclease 1, ATF4 and
      CCAAT-enhancer-binding protein (C/EBP)-homologous protein) suggesting activation
      of unfolded protein response pathway. Moreover, we found downregulation of
      phosphorylated Akt (Thr308 and Ser473), mammalian target of rapamycin (mTOR;
      Ser2448 and Ser2481) and 4E-BP1 (Thr37/46) by alpha-solanine implying suppression
      of the Akt/mTOR pathway. Collectively, our results signify that alpha-solanine
      induces autophagy to exert anti-proliferative activity by triggering ER stress
      and inhibiting Akt/mTOR signaling pathway.

PMID- 26313913
TI  - Decreased autophagy: a major factor for cardiomyocyte death induced by beta1
      adrenoceptor autoantibodies.
AB  - Cardiomyocyte death is one major factor in the development of heart dysfunction,
      thus, understanding its mechanism may help with the prevention and treatment of
      this disease. Previously, we reported that anti-beta1-adrenergic receptor
      autoantibodies (beta1-AABs) decreased myocardial autophagy, but the role of these
      in cardiac function and cardiomyocyte death is unclear. We report that rapamycin,
      an mTOR inhibitor, restored cardiac function in a passively beta1-AAB-immunized
      rat model with decreased cardiac function and myocardial autophagic flux. Next,
      after upregulating or inhibiting autophagy with Beclin-1 overexpression/rapamycin
      or RNA interference (RNAi)-mediated expression of Beclin-1/3-methyladenine, beta1
      AAB-induced autophagy was an initial protective stress response before apoptosis.
      Then, decreased autophagy contributed to cardiomyocyte death followed by
      decreases in cardiac function. In conclusion, proper regulation of autophagy may
      be important for treating patients with beta1-AAB-positive heart dysfunction. 

PMID- 26313914
TI  - HMGB1 in the pathogenesis of ultraviolet-induced ocular surface inflammation.
AB  - High-mobility group box 1 (HMGB1) functions as a transcription-enhancing nuclear
      protein as well as a crucial cytokine that regulates inflammation. This study
      demonstrated that secretion of HMGB1 due to ultraviolet (UV) radiation inducing
      ocular surface inflammation-mediated reactive oxygen species (ROS) production.
      After treating conjunctival epithelial cells with UV radiation, HMGB1 was
      translocated from the nucleus to the cytoplasm and then eventually to the
      extracellular space. HMGB1 played a crucial role in UV-induced conjunctival
      neutrophil infiltration, which subsided when mice were pretreated with the HMGB1
      inhibitors soluble receptor for advanced glycation endproducts (sRAGEs) and HMGB1
      A box protein. In case of using ROS quencher, there was decrease in UV-induced
      HMGB1 secretion in conjunctival epithelial cells and mice. Considering that UV
      induced chronic inflammation causes ocular surface change as pterygium, we have
      confirmed high HMGB1 translocation and ROS expression in human pterygium. Our
      findings therefore revealed a previously unknown mechanism of UV-induced ocular
      inflammation related to ROS and HMGB1 suggesting a new medical therapeutic
      target. 

PMID- 26313915
TI  - CD40 ligand induces RIP1-dependent, necroptosis-like cell death in low-grade
      serous but not serous borderline ovarian tumor cells.
AB  - Ovarian high-grade serous carcinomas (HGSCs) and invasive low-grade serous
      carcinomas (LGSCs) are considered to be distinct entities. In particular, LGSCs
      are thought to arise from non-invasive serous borderline ovarian tumors (SBOTs)
      and show poor responsiveness to conventional chemotherapy. The pro-apoptotic
      effects of CD40 ligand (CD40L) have been demonstrated in HGSC, though the
      underlying mechanisms are not fully understood. Conversely, the therapeutic
      potential of the CD40L-CD40 system has yet to be evaluated in LGSC. We now show
      that CD40 protein is focally expressed on tumor cells in two of five primary
      LGSCs compared with no expression in eight primary SBOTs. Treatment with CD40L or
      agonistic CD40 antibody decreased the viability of LGSC-derived MPSC1 and VOA1312
      cells, but not SBOT3.1 cells. Small interfering RNA (siRNA) targeting CD40 was
      used to show that it is required for these reductions in cell viability. CD40L
      treatment increased cleaved caspase-3 levels in MPSC1 cells though, surprisingly,
      neither pan-caspase inhibitor nor caspase-3 siRNA reversed or even attenuated
      CD40L-induced cell death. In addition, CD40-induced cell death was not affected
      by knockdown of the mitochondrial proteins apoptosis-inducing factor (AIF) and
      endonuclease G (EndoG). Interestingly, CD40L-induced cell death was blocked by
      necrostatin-1, an inhibitor of receptor-interacting protein 1 (RIP1), and
      attenuated by inhibitors of RIP3 (GSK'872) or MLKL (mixed lineage kinase domain
      like; necrosulfonamide). Our results indicate that the upregulation of CD40 may
      be relatively common in LGSC and that CD40 activation induces RIP1-dependent,
      necroptosis-like cell death in LGSC cells. 

PMID- 26313916
TI  - MicroRNA-26a supports mammalian axon regeneration in vivo by suppressing GSK3beta
      expression.
AB  - MicroRNAs are emerging to be important epigenetic factors that control axon
      regeneration. Here, we report that microRNA-26a (miR-26a) is a physiological
      regulator of mammalian axon regeneration in vivo. We demonstrated that endogenous
      miR-26a acted to target specifically glycogen synthase kinase 3beta (GSK3beta) in
      adult mouse sensory neurons in vitro and in vivo. Inhibition of endogenous miR
      26a in sensory neurons impaired axon regeneration in vitro and in vivo. Moreover,
      the regulatory effect of miR-26a was mediated by increased expression of GSK3beta
      because downregulation or pharmacological inhibition of GSK3beta fully rescued
      axon regeneration. Our results also suggested that the miR-26a-GSK3beta pathway
      regulated axon regeneration at the neuronal soma by controlling gene expression.
      We provided biochemical and functional evidences that the regeneration-associated
      transcription factor Smad1 acted downstream of miR-26a and GSK3beta to control
      sensory axon regeneration. Our study reveals a novel miR-26a-GSK3beta-Smad1
      signaling pathway in the regulation of mammalian axon regeneration. Moreover, we
      provide the first evidence that, in addition to inhibition of GSK3beta kinase
      activity, maintaining a lower protein level of GSK3beta in neurons by the
      microRNA is necessary for efficient axon regeneration. 

PMID- 26313918
TI  - The novel protective role of P27 in MLN4924-treated gastric cancer cells.
AB  - The tumor-suppressor gene cyclin-dependent kinase inhibitor 1B (P27) is
      downregulated in gastric cancer cells mainly through proteolytic degradation
      mediated by the SKP-Cullin1-F-Box (SCF) complex. But the correlation between its
      downregulation and gastric cancer prognosis still remains indefinite. MLN4924, an
      anti-tumor agent, which suppresses the SCF complex by inhibiting Cullin1
      neddylation, emerges as a promising tool to elucidate its functions in gastric
      cancer cells. In this study, MLN4924 induced significant growth inhibition of
      gastric cancer cells in a dose-dependent manner, along with the simultaneous
      accumulation of P27 and cell cycle abnormalities such as G2/M arrest.
      Importantly, we found that P27 silencing in MLN4924-treated cells resulted in an
      enhancement of growth inhibition both in vitro and in vivo. Mechanism analysis
      revealed the antagonism effects of antioxidants to this excess apoptosis,
      suggesting reactive oxygen species (ROS) overproduction especially in the
      mitochondria was the principal cause of the augmentation. Moreover, the robust
      ROS attacked the mitochondria to initiate collapse of the mitochondrial membrane
      permeability and the exportation of apoptosis-inducing factor (AIF), IAP-binding
      mitochondrial protein (SMAC/DIABLO) and cytochrome c. Finally, we also found that
      P27 knockdown affected the expression profile of several critical BH3 family
      members to amplify the mitochondrial dysfunction and apoptosis. In summary, our
      findings unveiled a protective role of P27 by maintaining mitochondrial membrane
      permeability in MLN4924-treated gastric cancer cells, and therefore highlighted
      the potential combination of MLN4924 with P27 inhibition to improve its
      therapeutic efficacy. 

PMID- 26313917
TI  - DED or alive: assembly and regulation of the death effector domain complexes.
AB  - Death effector domains (DEDs) are protein-protein interaction domains initially
      identified in proteins such as FADD, FLIP and caspase-8 involved in regulating
      apoptosis. Subsequently, these proteins have been shown to have important roles
      in regulating other forms of cell death, including necroptosis, and in regulating
      other important cellular processes, including autophagy and inflammation.
      Moreover, these proteins also have prominent roles in innate and adaptive
      immunity and during embryonic development. In this article, we review the various
      roles of DED-containing proteins and discuss recent developments in our
      understanding of DED complex formation and regulation. We also briefly discuss
      opportunities to therapeutically target DED complex formation in diseases such as
      cancer. 

PMID- 26313919
TI  - Transglutaminase 2--a novel inhibitor of adipogenesis.
AB  - Differentiation of preadipocytes to lipid storing adipocytes involves
      extracellular signaling pathways, matrix remodeling and cytoskeletal changes. A
      number of factors have been implicated in maintaining the preadipocyte state and
      preventing their differentiation to adipocytes. We have previously reported that
      a multifunctional and protein crosslinking enzyme, transglutaminase 2 (TG2) is
      present in white adipose tissue. In this study, we have investigated TG2 function
      during adipocyte differentiation. We show that TG2 deficient mouse embryonic
      fibroblasts (Tgm2-/- MEFs) display increased and accelerated lipid accumulation
      due to increased expression of major adipogenic transcription factors, PPARgamma
      and C/EBPalpha. Examination of Pref-1/Dlk1, an early negative regulator of
      adipogenesis, showed that the Pref-1/Dlk1 protein was completely absent in Tgm2-/
      MEFs during early differentiation. Similarly, Tgm2-/- MEFs displayed defective
      canonical Wnt/beta-catenin signaling with reduced beta-catenin nuclear
      translocation. TG2 deficiency also resulted in reduced ROCK kinase activity,
      actin stress fiber formation and increased Akt phosphorylation in MEFs, but did
      not alter fibronectin matrix levels or solubility. TG2 protein levels were
      unaltered during adipogenic differentiation, and was found predominantly in the
      extracellular compartment of MEFs and mouse WAT. Addition of exogenous TG2 to
      Tgm2+/+ and Tgm2-/- MEFs significantly inhibited lipid accumulation, reduced
      expression of PPARgamma and C/EBPalpha, promoted the nuclear accumulation of beta
      catenin, and recovered Pref-1/Dlk1 protein levels. Our study identifies TG2 as a
      novel negative regulator of adipogenesis. 

PMID- 26313921
TI  - A Complex Network Approach to Stylometry.
AB  - Statistical methods have been widely employed to study the fundamental properties
      of language. In recent years, methods from complex and dynamical systems proved
      useful to create several language models. Despite the large amount of studies
      devoted to represent texts with physical models, only a limited number of studies
      have shown how the properties of the underlying physical systems can be employed
      to improve the performance of natural language processing tasks. In this paper, I
      address this problem by devising complex networks methods that are able to
      improve the performance of current statistical methods. Using a fuzzy
      classification strategy, I show that the topological properties extracted from
      texts complement the traditional textual description. In several cases, the
      performance obtained with hybrid approaches outperformed the results obtained
      when only traditional or networked methods were used. Because the proposed model
      is generic, the framework devised here could be straightforwardly used to study
      similar textual applications where the topology plays a pivotal role in the
      description of the interacting agents. 

PMID- 26313920
TI  - Repetitive Glucose Spikes Accelerate Atherosclerotic Lesion Formation in C57BL/6
      Mice.
AB  - BACKGROUND: A number of epidemiological studies demonstrated that postprandial
      hyperglycemia is a risk factor for cardiovascular disease in individuals with
      impaired glucose tolerance. Although several laboratory studies have addressed
      the plausible causal role of postprandial acute hyperglycemia (glucose spikes) in
      the development of atherosclerosis, there is little convincing evidence in vivo
      whether the atherosclerotic lesion formation can be accelerated solely by glucose
      spikes. Here, we assessed the effect of repetitive glucose spikes on
      atherosclerotic lesion formation in mice. METHODS: Female C57BL/6 mice were fed
      an atherogenic diet from 8 to 28 weeks of age. During the atherogenic diet
      feeding period, the mice orally received a glucose solution (50 mg glucose/mouse;
      G group) or water (W group) twice daily, 6 days a week. Atherosclerotic lesion
      formation in the aortic sinus was quantitatively analyzed in serial cross
      sections by oil red O staining. RESULTS: G group mice showed transient increases
      in blood glucose level (~5 mmol/L above W group), and the levels returned to
      levels similar to those in W group mice within 60 min. No significant differences
      in glucose tolerance, insulin sensitivity, and plasma lipid profiles were
      observed after the 20-week repetitive administration between the 2 groups. G
      group mice showed an approximately 4-fold greater atherosclerotic lesion size in
      the aortic sinus than W group mice. Gene expression levels of Cd68 and Icam1 in
      the thoracic aorta were higher in G group mice than in W group mice. CONCLUSIONS:
      These results indicate that glucose spikes can accelerate atherosclerotic lesion
      formation, with little influence on other metabolic disorders. Repetitive glucose
      administration in wild-type mice may serve as a simple and useful approach to
      better understanding the causal role of glycemic spikes in the development of
      atherosclerosis.

PMID- 26313922
TI  - Controlled/Living Radical Polymerization in Dispersed Systems: An Update.

PMID- 26313923
TI  - Synthesis and Antiviral Evaluation of 1-[(2-Phenoxyethyl)oxymethyl] and 6-(3,5
      Dimethoxybenzyl) Analogues of HIV Drugs Emivirine and TNK-651.
AB  - Novel emivirine analogues 6a, b were synthesized by reacting chloromethyl ethyl
      ether with 5-ethyl/isopropyl-6-(3,5-dimethoxybenzyl)uracils 5e, f. On the other
      hand, A series of new TNK-651 analogues 10a-f substituted at N-1 with
      phenoxyethoxymethyl moiety was prepared on treatment of the corresponding uracils
      5a-f with bis(phenoxyethoxy)methane (9). The newly synthesized non-nucleosides
      were tested for antiviral activity against wild type HIV-1 IIIB as well as the
      resistant strains N119 (Y181C), A17 (K103N+Y181C), and the triple mutant EFV(R)
      (K103R+V179D+P225H) in MT-4 cells. Most of the tested compounds showed good
      activities. Among them 6-(3,5-dimethylbenzyl)-5-ethyl-1-[(2
      phenoxyethyl)oxymethyl]uracil (10c) and 6-(3,5-dimethylbenzyl)-5-isopropyl-1-[(2
      phenoxyethyl)oxymethyl]uracil (10d) that showed inhibitory potency higher than
      emivirine against both wild type HIV-1 and the tested mutant strains, as well as
      higher activity than efavirenz against EFV(R). 

PMID- 26313924
TI  - Improving Osteoporosis Management in Primary Care: An Audit of the Impact of a
      Community Based Fracture Liaison Nurse.
AB  - BACKGROUND: Osteoporosis and associated fragility fractures are a major health
      problem; they are more common in women over 50 years old. Fracture liaison nurses
      have been widely used in secondary care to promote the recognition of fragility
      fractures and to promote the use of bone-sparing medication to reduce the risk of
      recurrent facture. OBJECTIVE: Audit the impact of a primary care based fracture
      liaison nurse on the detection of fragility fractures in people with osteoporosis
      and their treatment with a bone-sparing medication. METHOD: This audit took place
      in 12 GP practices using 'before and after' cross-sectional extractions of
      anonymised routine data. We report, for females 50-74 years and >= 75 years old,
      socio-economic deprivation index, the prevalence of osteoporosis, recording of
      fragility fractures, dual-energy X-ray absorptiometry (DXA), smoking, and body
      mass index (BMI) and use of appropriate bone-sparing medication. We used Altman's
      test of independent proportions to compare before and after data. RESULTS:
      Recording of the diagnosis of osteoporosis increased from 1.5% to 1.7% (p =
      0.059); the rate of DXA scans fell (1.8% to 1.4%; p = 0.002); recording of
      fractures and fragility fractures more than doubled (0.8% to 2.0%; p<0.001 and
      0.5% to 1.5%; p<0.001, respectively) with approximate doubling of the recording
      of smoking, and BMI (p<0.001 level). Fragility fracture recording rose from 8.8%
      to 15% in females aged 50 to 74, and from 0.8% to 2.3% in people aged >= 75 years
      old (p<0.001). There appeared to be inequity in the service, people who were
      least deprived were more likely to receive DXA scans and the more deprived to be
      prescribed bone sparing agents. CONCLUSION: A fracture liaison nurse in primary
      care has been associated with a period of improved management. Liaison nurses
      based in different parts of the health system should be tested in a prospective
      trial.

PMID- 26313925
TI  - Advanced Microbial Taxonomy Combined with Genome-Based-Approaches Reveals that
      Vibrio astriarenae sp. nov., an Agarolytic Marine Bacterium, Forms a New Clade in
      Vibrionaceae.
AB  - Advances in genomic microbial taxonomy have opened the way to create a more
      universal and transparent concept of species but is still in a transitional stage
      towards becoming a defining robust criteria for describing new microbial species
      with minimum features obtained using both genome and classical polyphasic
      taxonomies. Here we performed advanced microbial taxonomies combined with both
      genome-based and classical approaches for new agarolytic vibrio isolates to
      describe not only a novel Vibrio species but also a member of a new Vibrio clade.
      Two novel vibrio strains (Vibrio astriarenae sp. nov. C7T and C20) showing
      agarolytic, halophilic and fermentative metabolic activity were isolated from a
      seawater sample collected in a coral reef in Okinawa. Intraspecific similarities
      of the isolates were identical in both sequences on the 16S rRNA and pyrH genes,
      but the closest relatives on the molecular phylogenetic trees on the basis of 16S
      rRNA and pyrH gene sequences were V. hangzhouensis JCM 15146T (97.8% similarity)
      and V. agarivorans CECT 5085T (97.3% similarity), respectively. Further
      multilocus sequence analysis (MLSA) on the basis of 8 protein coding genes (ftsZ,
      gapA, gyrB, mreB, pyrH, recA, rpoA, and topA) obtained by the genome sequences
      clearly showed the V. astriarenae strain C7T and C20 formed a distinct new clade
      protruded next to V. agarivorans CECT 5085T. The singleton V. agarivorans has
      never been included in previous MLSA of Vibrionaceae due to the lack of some gene
      sequences. Now the gene sequences are completed and analysis of 100 taxa in total
      provided a clear picture describing the association of V. agarivorans into pre
      existing concatenated network tree and concluded its relationship to our vibrio
      strains. Experimental DNA-DNA hybridization (DDH) data showed that the strains
      C7T and C20 were conspecific but were separated from all of the other Vibrio
      species related on the basis of both 16S rRNA and pyrH gene phylogenies (e.g., V.
      agarivorans CECT 5085T, V. hangzhouensis JCM 15146T V. maritimus LMG 25439T, and
      V. variabilis LMG 25438T). In silico DDH data also supported the genomic
      relationship. The strains C7T also had less than 95% average amino acid identity
      (AAI) and average nucleotide identity (ANI) towards V. maritimus C210, V.
      variabilis C206, and V. mediterranei AK1T, V. brasiliensis LMG 20546T, V.
      orientalis ATCC 33934T, and V. sinaloensis DSM 21326. The name Vibrio astriarenae
      sp. nov. is proposed with C7 as the type strains. Both V. agarivorans CECT 5058T
      and V. astriarenae C7T are members of the newest clade of Vibrionaceae named
      Agarivorans.

PMID- 26313926
TI  - The Effect of Disease-Induced Mortality on Structural Network Properties.
AB  - As the understanding of the importance of social contact networks in the spread
      of infectious diseases has increased, so has the interest in understanding the
      feedback process of the disease altering the social network. While many studies
      have explored the influence of individual epidemiological parameters and/or
      underlying network topologies on the resulting disease dynamics, we here provide
      a systematic overview of the interactions between these two influences on
      population-level disease outcomes. We show that the sensitivity of the population
      level disease outcomes to the combination of epidemiological parameters that
      describe the disease are critically dependent on the topological structure of the
      population's contact network. We introduce a new metric for assessing disease
      driven structural damage to a network as a population-level outcome. Lastly, we
      discuss how the expected individual-level disease burden is influenced by the
      complete suite of epidemiological characteristics for the circulating disease and
      the ongoing process of network compromise. Our results have broad implications
      for prediction and mitigation of outbreaks in both natural and human populations.

PMID- 26313927
TI  - Direct-to-consumer genetic testing: a systematic review of european guidelines,
      recommendations, and position statements.
AB  - BACKGROUND: Personalized healthcare is expected to yield promising results, with
      a paradigm shift toward more personalization in the practice of medicine. This
      emerging field has wide-ranging implications for all the stakeholders. Commercial
      tests in the form of multiplex genetic profiles are currently being provided to
      consumers, without the physicians' consultation, through the Internet, referred
      to as direct-to-consumer genetic tests (DTC GT). OBJECTIVES: The objective was to
      review all the existing European guidelines on DTC GT, and its associated
      interventions, to list all the supposed benefits and harms, issues and concerns,
      and recommendations. METHODS: We conducted a systematic review of position
      statements, policies, guidelines, and recommendations, produced by professional
      organizations or other relevant bodies for use of DTC GT in Europe. RESULTS:
      Seventeen documents met the inclusion criteria, which were subjected to thematic
      analysis, and the texts were coded for statements related to use of DTC GT.
      DISCUSSION AND CONCLUSIONS: Professional societies and associations are currently
      more suggestive of potential disadvantages of DTC GT, recommending improved
      genetic literacy of both populations and health professionals, and implementation
      research on the genetic tests to integrate public health genomics into healthcare
      systems.

PMID- 26313928
TI  - Escher: A Web Application for Building, Sharing, and Embedding Data-Rich
      Visualizations of Biological Pathways.
AB  - Escher is a web application for visualizing data on biological pathways. Three
      key features make Escher a uniquely effective tool for pathway visualization.
      First, users can rapidly design new pathway maps. Escher provides pathway
      suggestions based on user data and genome-scale models, so users can draw
      pathways in a semi-automated way. Second, users can visualize data related to
      genes or proteins on the associated reactions and pathways, using rules that
      define which enzymes catalyze each reaction. Thus, users can identify trends in
      common genomic data types (e.g. RNA-Seq, proteomics, ChIP)--in conjunction with
      metabolite- and reaction-oriented data types (e.g. metabolomics, fluxomics).
      Third, Escher harnesses the strengths of web technologies (SVG, D3, developer
      tools) so that visualizations can be rapidly adapted, extended, shared, and
      embedded. This paper provides examples of each of these features and explains how
      the development approach used for Escher can be used to guide the development of
      future visualization tools.

PMID- 26313929
TI  - Cooperation Improves Success during Intergroup Competition: An Analysis Using
      Data from Professional Soccer Tournaments.
AB  - The benefit mutually gained by cooperators is considered the ultimate explanation
      for why cooperation evolved among non-relatives. During intergroup competition,
      cooperative behaviours within groups that provide a competitive edge over their
      opposition should be favoured by selection, particularly in lethal human warfare.
      Aside from forming larger groups, three other ways that individuals within a
      group can cooperate to improve their chances of gaining a mutual benefit are: (i)
      greater networking, (ii) contributing more effort, and (iii) dividing labour.
      Greater cooperation is expected to increase the chances of gaining a group
      benefit by improving proficiency in the tasks critical to success-yet empirical
      tests of this prediction using real-world cases are absent. In this study, we
      used data derived from 12 international and professional soccer competitions to
      test the predictions that: 1) greater levels of cooperative behaviour are
      associated with winning group contests, 2) the three forms of cooperation differ
      in relative importance for winning matches, 3) competition and tournament-type
      affect the levels of cooperation and shooting proficiency in matches, and 4)
      greater levels of networking behaviour are associated with increased proficiency
      in the most critical task linked with winning success in soccer-shooting at goal.
      Winners were best predicted by higher shooting proficiency, followed by greater
      frequencies of networking interactions within a team but unexpectedly, fewer
      networking partners and less division of labour. Although significant variation
      was detected across competitions and tournament-types, greater levels of
      networking behaviour were consistently associated with increased proficiency in
      shooting at goal, which in turn was linked with winning success. This study
      empirically supports the idea that intergroup competition can favour cooperation
      among non-relatives. 

PMID- 26313930
TI  - The association of polymorphisms in DAT (40 bp VNTR, C>T 3'UTR) and DBH (-1021
      C/T) genes with the severe complications of alcohol withdrawal state.

PMID- 26313931
TI  - Gene-environment interactions in psychopathology throughout early childhood: a
      systematic review.
AB  - Up to 20% of children and adolescents worldwide suffer from mental health
      problems. Epidemiological studies have shown that some of these problems are
      already present at an early age. The recognition that psychopathology is a result
      of an interaction between individual experiences and genetic characteristics has
      led to an increase in the number of studies using a gene-environment approach
      (G*E). However, to date, there has been no systematic review of G*E studies on
      psychopathology in the first 6 years of life. Following a literature search and a
      selection process, 14 studies were identified and most (n=12) of the studies
      found at least one significant G*E effect. This review provides a systematic
      characterization of the published G*E studies, providing insights into the
      neurobiological and environmental determinants involved in the etiology of
      children's psychopathology. 

PMID- 26313932
TI  - Turning Supramolecular Receptors into Chemosensors by Nanoparticle-Assisted "NMR
      Chemosensing".
AB  - By exploiting a magnetization transfer between monolayer-protected nanoparticles
      and interacting analytes, the NMR chemosensing protocol provides a general
      approach to convert supramolecular receptors into chemosensors via their
      conjugation with nanoparticles. In this context, the nanoparticles provide the
      supramolecular receptor not only with the "bulkiness" necessary for the NMR
      chemosensing approach but also with a different selectivity as compared to the
      parent receptor. We here demonstrate that gold nanoparticles of 1.8 nm core
      coated with a monolayer of 18-crown-6 ether derivatives can detect and identify
      protonated primary amines in methanol and in water, and even discriminate between
      two biogenic diamines that are selectively detected over monoamines and alpha
      amino acids. 

PMID- 26313933
TI  - Successful aging among Chinese near-centenarians and centenarians in Hong Kong: a
      multidimensional and interdisciplinary approach.
AB  - OBJECTIVES: This study applied a multidimensional model on a continuum to examine
      successful aging (SA) and investigated whether SA is associated with biomedical
      and psychosocial-demographic factors among Hong Kong Chinese near-centenarians
      and centenarians. METHOD: A cross-sectional data analysis was performed on a
      geographically representative sample of 120 near-centenarians and centenarians
      with an age range of 95-108 years. We developed an integrated and cumulative
      Successful Aging Index (SAI) based on participants' performance in four
      dimensions: (1) physical and functional health (PF), (2) psychological well-being
      and cognition (PC), (3) social engagement and family support (SF), (4) economic
      resources and financial security (EF). To examine the criterion validity of SAI,
      we conducted a multiple binary logistic regression with interviewer-rated health.
      A multiple regression model was ran to investigate the independent biomedical and
      psychosocial-demographic correlates of SAI. RESULTS: Results show that only 5.8%
      of participants attained SA in all four dimensions. PF had the least achievers,
      whereas the proportion was the highest in PC. SAI was significantly associated
      with interviewer-rated health and a high level of high-density lipoprotein
      cholesterol. Living with family or friends, high level of optimism, fewer
      diseases, and barriers to social activities were independent predictors of SAI
      score. CONCLUSION: In the light of the lack of consensus on the constituents and
      assessment of SA especially among very old adults, our findings add to the extant
      literature by underscoring the importance of the multidimensional nature and the
      utility of an integrated and cumulative-based assessment of SA at the extreme of
      longevity.

PMID- 26313934
TI  - Ultra-trace measurement of Dechloranes to investigate food as a route of human
      exposure.
AB  - Dechloranes, including Dechlorane Plus (syn- and anti-isomers), Dechlorane 602,
      Dechlorane 603, Dechlorane 604, Chlordene Plus, and Mirex are used as flame
      retardants and were recently found in human serum of the European population. In
      order to investigate if food consumption would possibly be a significant route of
      exposure, we developed a method for the measurement of Dechloranes in food and
      feed. We showed that it was possible to extend the scope of the regular
      polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs),
      dioxin like (DL-), and non-dioxin like (NDL-) regulated PCBs clean-up and
      fractionation procedure to Dechloranes and that no compound degradation occurred
      during the strong acidic treatments used for lipid digestion. Dechloranes were
      measured by gas chromatography coupled to triple quadrupole mass spectrometry (GC
      QQQMS/MS). We optimized injection parameters by face centered experimental design
      (FCD). The electron ionization fragmentation was investigated to set appropriate
      multiple reaction monitoring (MRM) transitions. Instrumental and method limits of
      quantitation (iLOQs and mLOQs) were determined following EU guidelines for dioxin
      analyses in food. A total of 88 samples were analyzed to assess the prevalence of
      this route of exposure to humans. Average levels of the sum of Dechloranes ranged
      from 10 to 31pg/g fat, with the exception of fish, feed additives, and corn that
      were reported in pg/g wet weight at average levels of 9, 12, and 2pg/g ww. Based
      on Belgian food habits, a dietary intake was estimated to be 136pg/day. The
      relatively low reported levels indicate that other routes of human exposure
      should be considered.

PMID- 26313935
TI  - Effect of Bifidobacterium thermophilum RBL67 and fructo-oligosaccharides on the
      gut microbiota in Gottingen minipigs.
AB  - Modulating the gut microbiota via dietary interventions is a common strategy to
      enhance the natural defence mechanisms of the host. Several in vitro studies have
      highlighted the probiotic potential of Bifidobacterium thermophilum RBL67 (RBL67)
      selected for its anti-Salmonella effects. The present study aimed to investigate
      the impact of RBL67 alone and combined with fructo-oligosaccharides (FOS) on the
      gut microbiota of Gottingen minipigs. Minipigs were fed a basal diet supplemented
      with 8 g/d probiotic powder (1*109 CFU/g in skim milk matrix) (probiotic diet
      (PRO)), 8 g/d probiotic powder plus 8 g/d FOS (synbiotic diet (SYN)) or 8 g/d
      skim milk powder (control), following a cross-sectional study design. Faecal and
      caecal microbiota compositions were analysed with pyrosequencing of 16S rRNA
      genes and quantitative PCR. Metabolic activity in the caecum and colon was
      measured by HPLC. 16S rRNA gene amplicon sequencing revealed that minipig faeces
      show close similarity to pig microbiota. During the treatments and at the time of
      killing of animals, RBL67 was consistently detected in faeces, caecum and colon
      at numbers of 105-106 16S rRNA copies/g content after feeding PRO and SYN diets.
      At the time of killing of animals, significantly higher Bifidobacterium numbers
      in the caecum and colon of SYN-fed minipigs were measured compared with PRO. Our
      data indicate that the Gottingen minipig may be a suitable model for gut
      microbiota research in pigs. Data from this first in vivo study of RBL67
      colonisation suggest that the combination with FOS may represent a valuable
      symbiotic strategy to increase probiotic bacteria levels and survival in
      gastrointestinal tracts for feed and food applications. 

PMID- 26313937
TI  - Correction: Cellular Promyelocytic Leukemia Protein Is an Important Dengue Virus
      Restriction Factor.

PMID- 26313936
TI  - Nut consumption is inversely associated with both cancer and total mortality in a
      Mediterranean population: prospective results from the Moli-sani study.
AB  - Nut intake has been associated with reduced inflammatory status and lower risk of
      CVD and mortality. The aim of this study was to examine the relationship between
      nut consumption and mortality and the role of inflammation. We conducted a
      population-based prospective investigation on 19 386 subjects enrolled in the
      Moli-sani study. Food intake was recorded by the Italian version of the European
      Project Investigation into Cancer and Nutrition FFQ. C-reactive protein,
      leucocyte and platelet counts and the neutrophil:lymphocyte ratio were used as
      biomarkers of low-grade inflammation. Hazard ratios (HR) were calculated using
      multivariable Cox proportional hazard models. During a median follow-up of 4.3
      years, 334 all-cause deaths occurred. As compared with subjects who never ate
      nuts, rare intake (<=2 times/month) was inversely associated with mortality
      (multivariable HR=0.68; 95 % CI 0.54, 0.87). At intake >=8 times/month, a greater
      protection was observed (HR=0.53; 0.32, 0.90). Nut intake (v. no intake) conveyed
      a higher protection to individuals poorly adhering to the Mediterranean diet
      (MD). A significant reduction in cancer deaths (HR=0.64; 95 % CI 0.44, 0.94) was
      also observed, whereas the impact on CVD deaths was limited to an inverse, but
      not significant, trend. Biomarkers of low-grade inflammation were reduced in nut
      consumers but did not account for the association with mortality. In conclusion,
      nut intake was associated with reduced cancer and total mortality. The protection
      was stronger in individuals with lower adherence to MD, whereas it was similar in
      high-risk groups (diabetics, obese, smokers or those with the metabolic
      syndrome), as compared with low-risk subjects. Inflammation did not explain the
      observed relationship. 

PMID- 26313938
TI  - Extrapolation of Inter Domain Communications and Substrate Binding Cavity of
      Camel HSP70 1A: A Molecular Modeling and Dynamics Simulation Study.
AB  - Heat shock protein 70 (HSP70) is an important chaperone, involved in protein
      folding, refolding, translocation and complex remodeling reactions under normal
      as well as stress conditions. However, expression of HSPA1A gene in heat and cold
      stress conditions associates with other chaperons and perform its function.
      Experimental structure for Camel HSP70 protein (cHSP70) has not been reported so
      far. Hence, we constructed 3D models of cHSP70 through multi- template
      comparative modeling with HSP110 protein of S. cerevisiae (open state) and with
      HSP70 protein of E. coli 70kDa DnaK (close state) and relaxed them for 100
      nanoseconds (ns) using all-atom Molecular Dynamics (MD) Simulation. Two stable
      conformations of cHSP70 with Substrate Binding Domain (SBD) in open and close
      states were obtained. The collective mode analysis of different transitions of
      open state to close state and vice versa was examined via Principal Component
      Analysis (PCA) and Minimum Distance Matrix (MDM). The results provide mechanistic
      representation of the communication between Nucleotide Binding Domain (NBD) and
      SBD to identify the role of sub domains in conformational change mechanism, which
      leads the chaperone cycle of cHSP70. Further, residues present in the chaperon
      functioning site were also identified through protein-peptide docking. This study
      provides an overall insight into the inter domain communication mechanism and
      identification of the chaperon binding cavity, which explains the underlying
      mechanism involved during heat and cold stress conditions in camel. 

PMID- 26313939
TI  - Immunologic Predictors of Liver Transplantation Outcomes in HIV-HCV Co-Infected
      Persons.
AB  - Liver disease is a leading cause of mortality among HIV-infected persons in the
      highly active anti-retroviral therapy (HAART) era. Hepatitis C Virus (HCV) co
      infection is prevalent in, and worsened by HIV; consequently many co-infected
      persons require liver transplantation (LT). Despite the need, post-LT outcomes
      are poor in co-infection. We examined predictors of outcomes post-LT. Immunologic
      biomarkers of immune activation, microbial translocation, and Th1/Th2 skewing
      were measured pre-LT in participants enrolled in a cohort of HIV infected persons
      requiring solid organ transplant (HIVTR). Predictive biomarkers were analyzed in
      Cox-proportional hazards models; multivariate models included known predictors of
      outcome and biomarkers from univariate analyses. Sixty-nine HIV-HCV co-infected
      persons with available pre-LT samples were tested: median (IQR) CD4+ T-cell count
      was 286 (210-429) cells mm-3; 6 (9%) had detectable HIV RNA. Median (IQR) follow
      up was 2.1 (0.7-4.0) years, 29 (42%) people died, 35 (51%) had graft loss, 22
      (32%) were treated for acute rejection, and 14 (20%) had severe recurrent HCV. In
      multivariate models, sCD14 levels were significantly lower in persons with graft
      loss post-LT (HR 0.10 [95%CI 0.02-0.68]). IL-10 levels were higher in persons
      with rejection (HR 2.10 [95%CI 1.01-4.34]). No markers predicted severe recurrent
      HCV. Monocyte activation pre-LT may be mechanistically linked to graft health in
      HIV-HCV co-infection.

PMID- 26313940
TI  - Elevated Levels of Asymmetric Dimethylarginine (ADMA) in the Pericardial Fluid of
      Cardiac Patients Correlate with Cardiac Hypertrophy.
AB  - BACKGROUND: Pericardial fluid (PF) contains several biologically active
      substances, which may provide information regarding the cardiac conditions.
      Nitric oxide (NO) has been implicated in cardiac remodeling. We hypothesized that
      L-arginine (L-Arg) precursor of NO-synthase (NOS) and asymmetric dimethylarginine
      (ADMA), an inhibitor of NOS, are present in PF of cardiac patients and their
      altered levels may contribute to altered cardiac morphology. METHODS: L-Arg and
      ADMA concentrations in plasma and PF, and echocardiographic parameters of
      patients undergoing coronary artery bypass graft (CABG, n = 28) or valve
      replacement (VR, n = 25) were determined. RESULTS: We have found LV hypertrophy
      in 35.7% of CABG, and 80% of VR patients. In all groups, plasma and PF L-Arg
      levels were higher than that of ADMA. Plasma L-Arg level was higher in CABG than
      VR (75.7 +/- 4.6 MUmol/L vs. 58.1 +/- 4.9 MUmol/L, p = 0.011), whereas PF ADMA
      level was higher in VR than CABG (0.9 +/- 0.0 MUmol/L vs. 0.7 +/- 0.0 MUmol/L, p
      = 0.009). L-Arg/ADMA ratio was lower in the VR than CABG (VRplasma: 76.1 +/- 6.6
      vs. CABGplasma: 125.4 +/- 10.7, p = 0.004; VRPF: 81.7 +/- 4.8 vs. CABGPF: 110.4
      +/- 7.2, p = 0.009). There was a positive correlation between plasma L-Arg and
      ADMA in CABG (r = 0.539, p = 0.015); and plasma and PF L-Arg in CABG (r = 0.357,
      p = 0.031); and plasma and PF ADMA in VR (r = 0.529, p = 0.003); and PF L-Arg and
      ADMA in both CABG and VR (CABG: r = 0.468, p = 0.006; VR: r = 0.371, p = 0.034).
      The following echocardiographic parameters were higher in VR compared to CABG:
      interventricular septum (14.7 +/- 0.5 mm vs. 11.9 +/- 0.4 mm, p = 0.000);
      posterior wall thickness (12.6 +/- 0.3 mm vs. 11.5 +/- 0.2 mm, p = 0.000); left
      ventricular (LV) mass (318.6 +/- 23.5 g vs. 234.6 +/- 12.3 g, p = 0.007); right
      ventricular (RV) (33.9 +/- 0.9 cm2 vs. 29.7 +/- 0.7 cm2, p = 0.004); right atrial
      (18.6 +/- 1.0 cm2 vs. 15.4 +/- 0.6 cm2, p = 0.020); left atrial (19.8 +/- 1.0 cm2
      vs. 16.9 +/- 0.6 cm2, p = 0.033) areas. There was a positive correlation between
      plasma ADMA and RV area (r = 0.453, p = 0.011); PF ADMA and end-diastolic (r =
      0.434, p = 0.015) and systolic diameter of LV (r = 0.487, p = 0.007); and
      negative correlation between PF ADMA and LV ejection fraction (r = -0.445, p =
      0.013) in VR. CONCLUSION: We suggest that elevated levels of ADMA in the PF of
      patients indicate upregulated RAS and reduced bioavailability of NO, which can
      contribute to the development of cardiac hypertrophy and remodeling.

PMID- 26313941
TI  - Joint and Independent Associations of Gestational Weight Gain and Pre-Pregnancy
      Body Mass Index with Outcomes of Pregnancy in Chinese Women: A Retrospective
      Cohort Study.
AB  - OBJECTIVE: To explore the joint and independent effects of gestational weight
      gain (GWG) and pre-pregnancy body mass index (BMI) on pregnancy outcomes in a
      population of Chinese Han women and to evaluate pregnant women's adherence to the
      2009 Institute of Medicine (IOM) gestational weight gain guidelines. METHODS:
      This was a multicenter, retrospective cohort study of 48,867 primiparous women
      from mainland China who had a full-term singleton birth between January 1, 2011
      and December 30, 2011. The independent associations of pre-pregnancy BMI, GWG and
      categories of combined pre-pregnancy BMI and GWG with outcomes of interest were
      examined using an adjusted multivariate regression model. In addition, women with
      pre-pregnancy hypertension were excluded from the analysis of the relationship
      between GWG and delivery of small-for-gestational-age (SGA) infants, and women
      with gestational diabetes (GDM) were excluded from the analysis of the
      relationship between GWG and delivery of large-for-gestational-age (LGA) infants.
      RESULTS: Only 36.8% of the women had a weight gain that was within the
      recommended range; 25% and 38.2% had weight gains that were below and above the
      recommended range, respectively. The contribution of GWG to the risk of adverse
      maternal and fetal outcomes was modest. Women with excessive GWG had an increased
      likelihood of gestational hypertension (adjusted OR 2.55; 95% CI = 1.92-2.80),
      postpartum hemorrhage (adjusted OR 1.30; 95% CI = 1.17-1.45), cesarean section
      (adjusted OR 1.31; 95% CI = 1.18-1.36) and delivery of an LGA infant (adjusted OR
      2.1; 95% CI = 1.76-2.26) compared with women with normal weight gain. Conversely,
      the incidence of GDM (adjusted OR 1.64; 95% CI = 1.20-1.85) and SGA infants
      (adjusted OR 1.51; 95% CI = 1.32-1.72) was increased in the group of women with
      inadequate GWG. Moreover, in the obese women, excessive GWG was associated with
      an apparent increased risk of delivering an LGA infant. In the women who were
      underweight, poor weight gain was associated with an increased likelihood of
      delivering an SGA infant. After excluding the mothers with GDM or gestational
      hypertension, the ORs for delivery of LGA and SGA infants decreased for women
      with high GWG and increased for women with low GWG. CONCLUSIONS: GWG above the
      recommended range is common in this population and is associated with multiple
      unfavorable outcomes independent of pre-pregnancy BMI. Obese women may benefit
      from avoiding weight gain above the range recommended by the 2009 IOM.
      Underweight women should avoid low GWG to prevent delivering an SGA infant.
      Pregnant women should therefore be monitored to comply with the IOM
      recommendations and should have a balanced weight gain that is within a range
      based on their pre-pregnancy BMI.

PMID- 26313943
TI  - A Deep-Structured Conditional Random Field Model for Object Silhouette Tracking.
AB  - In this work, we introduce a deep-structured conditional random field (DS-CRF)
      model for the purpose of state-based object silhouette tracking. The proposed DS
      CRF model consists of a series of state layers, where each state layer spatially
      characterizes the object silhouette at a particular point in time. The
      interactions between adjacent state layers are established by inter-layer
      connectivity dynamically determined based on inter-frame optical flow. By
      incorporate both spatial and temporal context in a dynamic fashion within such a
      deep-structured probabilistic graphical model, the proposed DS-CRF model allows
      us to develop a framework that can accurately and efficiently track object
      silhouettes that can change greatly over time, as well as under different
      situations such as occlusion and multiple targets within the scene. Experiment
      results using video surveillance datasets containing different scenarios such as
      occlusion and multiple targets showed that the proposed DS-CRF approach provides
      strong object silhouette tracking performance when compared to baseline methods
      such as mean-shift tracking, as well as state-of-the-art methods such as context
      tracking and boosted particle filtering. 

PMID- 26313942
TI  - Bioinformatics Analysis of the Complete Genome Sequence of the Mango Tree
      Pathogen Pseudomonas syringae pv. syringae UMAF0158 Reveals Traits Relevant to
      Virulence and Epiphytic Lifestyle.
AB  - The genome sequence of more than 100 Pseudomonas syringae strains has been
      sequenced to date; however only few of them have been fully assembled, including
      P. syringae pv. syringae B728a. Different strains of pv. syringae cause different
      diseases and have different host specificities; so, UMAF0158 is a P. syringae pv.
      syringae strain related to B728a but instead of being a bean pathogen it causes
      apical necrosis of mango trees, and the two strains belong to different
      phylotypes of pv.syringae and clades of P. syringae. In this study we report the
      complete sequence and annotation of P. syringae pv. syringae UMAF0158 chromosome
      and plasmid pPSS158. A comparative analysis with the available sequenced genomes
      of other 25 P. syringae strains, both closed (the reference genomes DC3000, 1448A
      and B728a) and draft genomes was performed. The 5.8 Mb UMAF0158 chromosome has
      59.3% GC content and comprises 5017 predicted protein-coding genes.
      Bioinformatics analysis revealed the presence of genes potentially implicated in
      the virulence and epiphytic fitness of this strain. We identified several genetic
      features, which are absent in B728a, that may explain the ability of UMAF0158 to
      colonize and infect mango trees: the mangotoxin biosynthetic operon mbo, a gene
      cluster for cellulose production, two different type III and two type VI
      secretion systems, and a particular T3SS effector repertoire. A mutant strain
      defective in the rhizobial-like T3SS Rhc showed no differences compared to wild
      type during its interaction with host and non-host plants and worms. Here we
      report the first complete sequence of the chromosome of a pv. syringae strain
      pathogenic to a woody plant host. Our data also shed light on the genetic factors
      that possibly determine the pathogenic and epiphytic lifestyle of UMAF0158. This
      work provides the basis for further analysis on specific mechanisms that enable
      this strain to infect woody plants and for the functional analysis of host
      specificity in the P. syringae complex. 

PMID- 26313944
TI  - Evolution of Cooperation on Spatial Network with Limited Resource.
AB  - Considering the external resource offered by environment is limited, here, we
      will explore the cooperation on spatial networks with limited resource. The
      individual distributes the limited resource according to the payoffs acquired in
      games, and one with resource amounts is lower than critical survival resource
      level will be replaced by the offspring of its neighbors. We find that, for
      larger temptation to defect, the number of the dead decreases with the resource
      amount. However the cooperation behavior is interesting, the lower total resource
      and intermediate temptation to defect can greatly promote the cooperation on
      square lattice. Our result reveals that the limited resource contributes most to
      the cooperation. 

PMID- 26313945
TI  - Identification and Evaluation of Reference Genes for Quantitative Analysis of
      Brazilian Pine (Araucaria angustifolia Bertol. Kuntze) Gene Expression.
AB  - Quantitative analysis of gene expression is a fundamental experimental approach
      in many fields of plant biology, but it requires the use of internal controls
      representing constitutively expressed genes for reliable transcript
      quantification. In this study, we identified fifteen putative reference genes
      from an A. angustifolia transcriptome database. Variation in transcript levels
      was first evaluated in silico by comparing read counts and then by quantitative
      real-time PCR (qRT-PCR), resulting in the identification of six candidate genes.
      The consistency of transcript abundance was also calculated applying geNorm and
      NormFinder software packages followed by a validation approach using four target
      genes. The results presented here indicate that a diverse set of samples should
      ideally be used in order to identify constitutively expressed genes, and that the
      use of any two reference genes in combination, of the six tested genes, is
      sufficient for effective expression normalization. Finally, in agreement with the
      in silico prediction, a comprehensive analysis of the qRT-PCR data combined with
      validation analysis revealed that AaEIF4B-L and AaPP2A are the most suitable
      reference genes for comparative studies of A. angustifolia gene expression. 

PMID- 26313947
TI  - Graphene Quantum Dots-based Photoluminescent Sensor: A Multifunctional Composite
      for Pesticide Detection.
AB  - Due to their size and difficulty to obtain, cost/effective biological or
      synthetic receptors (e.g., antibodies or aptamers, respectively), organic toxic
      compounds (e.g., less than 1 kDa) are generally challenging to detect using
      simple platforms such as biosensors. This study reports on the synthesis and
      characterization of a novel multifunctional composite material, magnetic silica
      beads/graphene quantum dots/molecularly imprinted polypyrrole (mSGP). mSGP is
      engineered to specifically and effectively capture and signal small molecules due
      to the synergy among chemical, magnetic, and optical properties combined with
      molecular imprinting of tributyltin (291 Da), a hazardous compound, selected as a
      model analyte. Magnetic and selective properties of the mSGP composite can be
      exploited to capture and preconcentrate the analyte onto its surface, and its
      photoluminescent graphene quantum dots, which are quenched upon analyte
      recognition, are used to interrogate the presence of the contaminant. This
      multifunctional material enables a rapid, simple and sensitive platform for small
      molecule detection, even in complex mediums such as seawater, without any sample
      treatment. 

PMID- 26313946
TI  - The "Reading the Mind in the Eyes" Test: Complete Absence of Typical Sex
      Difference in ~400 Men and Women with Autism.
AB  - The "Reading the Mind in the Eyes" test (Eyes test) is an advanced test of theory
      of mind. Typical sex difference has been reported (i.e., female advantage).
      Individuals with autism show more difficulty than do typically developing
      individuals, yet it remains unclear how this is modulated by sex, as females with
      autism have been under-represented. Here in a large, non-male-biased sample we
      test for the effects of sex, diagnosis, and their interaction. The Eyes test
      (revised version) was administered online to 395 adults with autism (178 males,
      217 females) and 320 control adults (152 males, 168 females). Two-way ANOVA
      showed a significant sex-by-diagnosis interaction in total correct score
      (F(1,711) = 5.090, p = 0.024, etap2 = 0.007) arising from a significant sex
      difference between control males and females (p < 0.001, Cohen's d = 0.47), and
      an absence of a sex difference between males and females with autism (p = 0.907,
      d = 0.01); significant case-control differences were observed across sexes, with
      effect sizes of d = 0.35 in males and d = 0.69 in females. Group-difference
      patterns fit with the extreme-male-brain (EMB) theory predictions. Eyes test
      Empathy Quotient and Eyes test-Autism Spectrum Quotient correlations were
      significant only in females with autism (r = 0.35, r = -0.32, respectively), but
      not in the other 3 groups. Support vector machine (SVM) classification based on
      response pattern across all 36 items classified autism diagnosis with a
      relatively higher accuracy for females (72.2%) than males (65.8%). Nevertheless,
      an SVM model trained within one sex generalized equally well when applied to the
      other sex. Performance on the Eyes test is a sex-independent phenotypic
      characteristic of adults with autism, reflecting sex-common social difficulties,
      and provides support for the EMB theory predictions for both males and females.
      Performance of females with autism differed from same-sex controls more than did
      that of males with autism. Females with autism also showed stronger coherence
      between self-reported dispositional traits and Eyes test performance than all
      other groups. 

PMID- 26313948
TI  - Investigating the Mg-Si Binary System via Combinatorial Sputter Deposition As
      High Energy Density Anodes for Lithium-Ion Batteries.
AB  - Mg-Si thin films with various elemental compositions ranging from 0<=x<=1 in
      MgxSi(1-x) were obtained via combinatorial magnetron sputter deposition of Si and
      Mg in order to improve the electrochemical lithiation/delithiation process of
      pure Si by embedding Si in an active Mg-Si matrix. Scanning electron microscopy,
      energy-dispersive X-ray spectroscopy, X-ray diffraction, and Raman spectroscopy
      methods were used to investigate the morphology, stoichiometry, and structure of
      the different thin film samples. Constant current charge/discharge cycling
      revealed significant electrochemical changes depending on the Mg content in
      comparison to the pure Si active material improving the capacity retention to 96%
      over 400 cycles.

PMID- 26313949
TI  - Mating Disruption for the 21st Century: Matching Technology With Mechanism.
AB  - Progress toward proof of the principal cause of insect mating disruption under a
      particular set of conditions has been hindered by a lack of logical rigor and
      clean falsifications of possible explanations. Here we make the case that
      understanding of mating disruption and optimization of particular formulations
      can be significantly advanced by rigorous application of the principles of strong
      inference. To that end, we offer a dichotomous key for eight distinct categories
      of mating disruption and detail criteria and methodologies for differentiating
      among them. Mechanisms of mating disruption closely align with those established
      for enzyme inhibition, falling into two major categories-competitive and
      noncompetitive. Under competitive disruption, no impairments are experienced by
      males, females, or the signal of females. Therefore, males can respond to females
      and traps. Competitive disruption is entirely a numbers game where the ratio of
      dispensers to females and traps is highly consequential and renders the control
      pest-density-dependent. Under noncompetitive disruption, males, females, or the
      signal from females are already impaired when sexual activity commences. The
      control achieved noncompetitively offers the notable advantage of being pest
      density-independent. Dosage-response curves are the best way to distinguish
      competitive from noncompetitive disruption. Purely competitive disruption
      produces: a smoothly concave curve when untransformed capture data are plotted on
      the y-axis against density of dispensers on the x-axis; a straight line with
      positive slope when the inverse of catch is plotted against density of pheromone
      dispensers; and, a straight line with negative slope when catch is plotted
      against density of pheromone dispensers * catch. Disruption operating only
      noncompetitively produces: a straight line with negative slope when untransformed
      capture data are plotted on the y-axis against density of dispensers on the x
      axis; an upturning curve when the inverse of catch is plotted against density of
      pheromone dispensers; and, a recurving plot when catch is plotted against density
      of pheromone dispensers x catch. Hybrid profiles are possible when some males
      within the population begin the activity period already incapacitated, while
      those not preexposed have the capacity to respond either to traps or pheromone
      dispensers. Competitive mechanisms include competitive attraction, induced
      allopatry, and induced arrestment. Noncompetitive mechanisms include
      desensitization and inhibition, induced allochrony, suppressed calling and
      mating, camouflage, and sensory imbalance. Examples of the various disruption
      types within the two major categories and suggested tactics for differentiating
      among them are offered as seven case studies of the disruption of important pest
      species using various formulations are analyzed in depth. We point out how
      economic optimizations may be achieved once the principal and contributory causes
      of disruption are proven. Hopefully, these insights will pave the way to a
      broader and more reliable usage of this environmentally friendly pest management
      tactic. 

PMID- 26313950
TI  - Anopheles darlingi (Diptera: Culicidae) Dynamics in Relation to Meteorological
      Data in a Cattle Farm Located in the Coastal Region of French Guiana: Advantage
      of Mosquito Magnet Trap.
AB  - Information on dynamics of anopheline mosquitoes is limited in the coastal zone
      of French Guiana compared with inland endemic areas. Importantly, improvement of
      surveillance techniques for assessing malaria transmission indicators and
      comprehension of impact of meteorological factors on Anopheles darlingi Root, the
      main malaria vector, are necessary. Anopheline mosquitoes were collected
      continuously during 2012 and 2013 using Mosquito Magnet traps baited with octenol
      and human landing catches. The two methods were compared based on trends in
      abundance and parity rate of An. darlingi. Impact of meteorological factors on
      An. darlingi density estimates was investigated using Spearman's correlation and
      by binomial negative regression analysis. In all, 11,928 anopheline mosquitoes
      were collected, and 90.7% (n = 10,815) were identified consisting of four
      species, with An. darlingi making up 94.9% (n = 10,264). An. darlingi specimens
      collected by the two methods were significantly correlated, and no difference in
      parity rate was observed. The abundance of this species peaked in September (dry
      season) and variations along the years were influenced by relative humidity,
      temperature, rainfall, and wind speed. Number of mosquitoes collected during peak
      aggression period was influenced by wind speed and rainfall. Data gathered in
      this study provide fundamental information about An. darlingi, which can
      facilitate the design of vector control strategies and construction of models for
      predicting malaria risk.

PMID- 26313951
TI  - Population Dynamics of an Insect Herbivore over 32 Years are Driven by
      Precipitation and Host-Plant Effects: Testing Model Predictions.
AB  - The interaction between the arroyo willow, Salix lasiolepis Bentham, and its
      specialist herbivore, the arroyo willow stem-galling sawfly, Euura lasiolepis
      Smith (Hymenoptera: Tenthredinidae), was studied for 32 yr in Flagstaff, AZ,
      emphasizing a mechanistic understanding of insect population dynamics. Long-term
      weather records were evaluated to provide a climatic context for this study.
      Previously, predictive models of sawfly dynamics were developed from estimates of
      sawfly gall density made between 1981 and 2002; one model each for drier and
      wetter sites. Predictor variables in these models included winter precipitation
      and the Palmer Drought Severity Index, which impact the willow growth, with
      strong bottom-up effects on sawflies. We now evaluate original model predictions
      of sawfly population dynamics using new data (from 2003-2012). Additionally,
      willow resources were evaluated in 1986 and in 2012, using as criteria clone
      area, shoot density, and shoot length. The dry site model accounted for 40% of
      gall population density variation between 2003 and 2012 (69% over the 32 yr),
      providing strong support for the bottom-up, mechanistic hypothesis that water
      supply to willow hosts impacts sawfly populations. The current drying trend
      stressed willow clones: in drier sites, willow resources declined and gall
      density decreased by 98%. The wet site model accounted for 23% of variation in
      gall population density between 2003 and 2012 (48% over 30 yr), consistent with
      less water limitation. Nonetheless, gall populations were reduced by 72%.

PMID- 26313952
TI  - Edge Effects Influence the Abundance of the Invasive Halyomorpha halys
      (Hemiptera: Pentatomidae) in Woody Plant Nurseries.
AB  - The invasive brown marmorated stink bug, Halyomorpha halys (Stal), has caused
      severe economic losses in the United States and is also a major nuisance pest
      invading homes. In diverse woody plant nurseries, favored host plants may be
      attacked at different times of the season and in different locations in the
      field. Knowledge of factors influencing H. halys abundance and simple methods to
      predict where H. halys are found and cause damage are needed to develop effective
      management strategies. In this study, we examined H. halys abundance on plants in
      tree nurseries as a function of distance from field edges (edge and core samples)
      and documented the abundance in tree nurseries adjoining different habitat types
      (corn, soybean, residential areas, and production sod). We conducted timed counts
      for H. halys on 2,016 individual trees belonging to 146 unique woody plant
      cultivars at two commercial tree nurseries in Maryland. Across three years of
      sampling, we found that H. halys nymphs and adults were more abundant at field
      edges (0-5 m from edges) than in the core of fields (15-20 m from edges).
      Proximity of soybean fields was associated with high nymph and adult abundance.
      Results indicate that monitoring efforts and intervention tactics for this
      invasive pest could be restricted to field edges, especially those close to
      soybean fields. We show clearly that spatial factors, especially distance from
      edge, strongly influence H. halys abundance in nurseries. This information may
      greatly simplify the development of any future management strategies.

PMID- 26313953
TI  - Contrasting Patterns of Host Adaptation in Two Egg Parasitoids of the Pine
      Processionary Moth (Lepidoptera: Thaumetopoeidae).
AB  - Adaptation of parasitoids to their phytophagous host is often mediated by
      environmental conditions and by the food plant of the phytophagous host.
      Therefore, the host food plant can indirectly affect the survival and fitness of
      parasitoids that also attack quiescent host stages, such as eggs, in which the
      resources available to the immature parasitoid stages are limited. Our aim was to
      investigate how two egg parasitoid species of the pine processionary moth,
      Thaumetopoea pityocampa (Denis & Schiffermuller), respond to variations in egg
      traits at the extremes of a west-to-east geographic gradient in northern Italy.
      We considered one specialist [Baryscapus servadeii (Domenichini)] and one
      generalist [Ooencyrtus pityocampae (Mercet)] parasitoid, which reproduce mainly
      by thelytokous parthenogenesis and are common throughout the whole range of this
      pest. The size and shell structure of the pine processionary moth eggs were
      studied under light microscopy and tested experimentally under controlled
      conditions. We can conclude that 1) the pine processionary moth egg shell
      thickness is inversely proportional to the parasitism performance; 2) the larger
      eggs from the pine processionary moth eastern population produce parasitoid
      females of a larger size, which have greater realized fecundity; 3) the
      generalist parasitoid performs successfully with either the "home" or "away"
      (i.e., from both extremes of the geographic gradient) pine processionary moth
      eggs, which is not the case for the specialist parasitoid. The implications of
      these responses in the regulation of phytophagous populations are numerous and
      should be considered in population dynamics studies and pest management programs.

PMID- 26313954
TI  - Survey of Soybean Insect Pollinators: Community Identification and Sampling
      Method Analysis.
AB  - Soybean, Glycine max (L.) Merrill, flowers can be a source of nectar and pollen
      for honey bees, Apis mellifera L. (Hymenoptera: Apidae), wild social and solitary
      bees (Hymenoptera: Apoidea), and flower-visiting flies (Diptera). Our objectives
      were to describe the pollinator community in soybean fields, determine which
      sampling method is most appropriate for characterizing their abundance and
      diversity, and gain insight into which pollinator taxa may contact soybean
      pollen. We compared modified pan traps (i.e., bee bowls), yellow sticky traps,
      and sweep nets for trapping pollinators in Iowa soybean fields when soybeans were
      blooming (i.e., reproductive stages R1-R6) during 2011 and 2012. When all trap
      type captures were combined, we collected 5,368 individuals and at least 50
      species. Per trap type, the most pollinators were captured in bee bowls (3,644
      individuals, 44 species), yellow sticky traps (1,652 individuals, 32 species),
      and sweep nets (66 individuals, 10 species). The most abundant species collected
      include Agapostemon virescens F. and Lasioglossum (Dialictus) species
      (Hymenoptera: Halictidae), Melissodes bimaculata Lepeletier (Hymenoptera:
      Apidae), and Toxomerus marginatus Say (Diptera: Syrphidae). To determine if these
      pollinators were foraging on soybean flowers, we looked for soybean pollen on the
      most abundant bee species collected that had visible pollen loads. We found
      soybean pollen alone or intermixed with pollen grains from other plant species on
      29 and 38% of the bees examined in 2011 and 2012, respectively. Our data suggest
      a diverse community of pollinators-composed of mostly native, solitary bees-visit
      soybean fields and forage on their flowers within Iowa. 

PMID- 26313955
TI  - Importance of Habitat Heterogeneity in Richness and Diversity of Moths
      (Lepidoptera) in Brazilian Savanna.
AB  - Moths exhibit different levels of fidelity to habitat, and some taxa are
      considered as bioindicators for conservation because they respond to habitat
      quality, environmental change, and vegetation types. In this study, we verified
      the effect of two phytophysiognomies of the Cerrado, savanna and forest, on the
      diversity distribution of moths of Erebidae (Arctiinae), Saturniidae, and
      Sphingidae families by using a hierarchical additive partitioning analysis. This
      analysis was based on two metrics: species richness and Shannon diversity index.
      The following questions were addressed: 1) Does the beta diversity of moths
      between phytophysiognomies add more species to the regional diversity than the
      beta diversity between sampling units and between sites? 2) Does the distribution
      of moth diversity differ among taxa? Alpha and beta diversities were compared
      with null models. The additive partitioning of species richness for the set of
      three Lepidoptera families identified beta diversity between phytophysiognomies
      as the component that contributed most to regional diversity, whereas the Shannon
      index identified alpha diversity as the major contributor. According to both
      species richness and the Shannon index, beta diversity between phytophysiognomies
      was significantly higher than expected by chance. Therefore, phytophysiognomies
      are the most important component in determining the richness and composition of
      the community. Additive partitioning also indicated that individual families of
      moths respond differently to the effect of habitat heterogeneity. The integrity
      of the Cerrado mosaic of phytophysiognomies plays a crucial role in maintaining
      moth biodiversity in the region. 

PMID- 26313956
TI  - The Spider Assemblage of Olive Groves Under Three Management Systems.
AB  - Olives, Olea europaea L., are one of the most important crops in Spain. They are
      currently produced under three management systems that involve different aspects
      of soil and pest management, productivity, and crop economy: organic, (integrated
      pest management-IPM), and conventional. Here, we studied how these systems affect
      the spiders, the natural enemies of olive grove pests, and performed a detailed
      analysis of their assemblage. The study was performed during one season in 18
      olive groves in Andalusia, Spain, and included both ground-dwelling and canopy
      species. We found that the organic system supported a significantly higher level
      of abundance and diversity of canopy spiders than the IPM and conventional
      systems. Plowing had a negative effect on spider abundance and diversity.
      However, the presence of hedge vegetation had a positive effect on the spiders.
      The practices affected the guild structure differently, with some guilds
      supported by organic and others by IPM. It is suggested that sustainability (in
      terms of pest control) in olive grove agroecosystems may be obtained by
      maintaining hedge vegetation regardless of the management system. 

PMID- 26313957
TI  - Predator-Prey Interactions are Context Dependent in a Grassland Plant-Grasshopper
      Wolf Spider Food Chain.
AB  - Species interactions are often context dependent, where outcomes vary in response
      to one or more environmental factors. It remains unclear how abiotic conditions
      like temperature combine with biotic factors such as consumer density or food
      quality to affect resource availability or influence species interactions. Using
      the large grasshopper Melanoplus bivittatus (Say) and a common wolf spider
      [Rabidosa rabida (Walkenaer)], we conducted manipulative field experiments in
      tallgrass prairie to examine how spider-grasshopper interactions respond to
      manipulations of temperature, grasshopper density, and food quality. Grasshopper
      survival was density dependent, as were the effects of spider presence and food
      quality in context-dependent ways. In high grasshopper density treatments,
      predation resulted in increased grasshopper survival, likely as a result of
      reduced intraspecific competition in the presence of spiders. Spiders had no
      effect on grasshopper survival when grasshoppers were stocked at low densities.
      Effects of the experimental treatments were often interdependent so that effects
      were only observed when examined together with other treatments. The occurrence
      of trophic cascades was context dependent, where the effects of food quality and
      spider presence varied with temperature under high-density treatments.
      Temperature weakly affected the impact of spider presence on M. bivittatus
      survivorship when all treatments were considered simultaneously, but different
      context-dependent responses to spider presence and food quality were observed
      among the three temperature treatments under high-density conditions. Our results
      indicate that context-dependent species interactions are common and highlight the
      importance of understanding how key biotic and abiotic factors combine to
      influence species interactions. 

PMID- 26313958
TI  - Effects of Season and Management of Irrigated Cotton Fields on Collembola
      (Hexapoda) in New South Wales, Australia.
AB  - The effects of production practices on the relative abundance of springtails
      (Collembola) in irrigated cotton fields of northern New South Wales (NSW) were
      studied over 2 yr to examine effects of farm management on these decomposer
      organisms. Pitfall trapping and soil core extraction was undertaken in both
      pseudoreplicated plots within whole fields on cotton farms and on experimental
      replicate plots of Envirofeast cotton and Lucerne. The relative abundance of
      surface-active springtails in cotton rows and densities of soil species from the
      rhizosphere were calculated. Twenty-three species of Collembola were collected
      from 5 fields, 19 in pitfall traps, and 11 in soil cores. Five species,
      Setogaster sp., Proisotoma minuta, Entomobrya unostrigata, Entomobrya
      multifasciata grp, and Lepidobrya sp. were numerically dominant on the ground at
      86-96% of individuals and Mesaphorura sp., Folsomides parvulus, and Hemisotoma
      thermophila grp dominant in the soil. Native grassland samples contained 15
      species of which a probable 10 were native and 8 were not found in cotton.
      Nineteen species of the 24 species identified from cotton were predominantly
      fungal feeders. Highest catches of Collembola occurred after flowering and soil
      Collembola increased with depth and during cotton growth on unsprayed plots but
      decreased on sprayed plots. Surface soil moistures affected daily catch rates
      with decomposing residues, crop stage, predator abundance, and season as
      secondary factors. Insecticide (endosulfan, pyrethroid, carbamate, and
      organophosphate) and predator effects were either negligible or unclear depending
      on the factor involved. Springtails appear to be predominately food limited
      during times of adequate soil moisture in cotton fields.

PMID- 26313959
TI  - Termite Assemblage Pattern and Niche Partitioning in a Tropical Forest Ecosystem.
AB  - Termites are major plant decomposers in tropical forest ecosystems, but their
      cryptic nature poses an obstacle for studying their ecological roles in depth. In
      the current study, we quantified climatic and geographic information of 137
      termite collection sites in the Kenting National Park, Taiwan, and described the
      ecological niches and assemblage patterns of 13 termite species of three
      families. Three major assemblage patterns are reported. First, the three termite
      families were found in most landcovering types with similar number of species,
      which indicated that each family played a unique role in the ecosystem. Second,
      average numbers of termite species were not different among collection sites, but
      the total number of termite species found in each landcovering type was
      different, which indicated that termite niche capacity in each small area was the
      same but some landcovering types were composed of diverse microhabitats to host
      more termite species. Third, termite species of every family showed distinct
      moisture preferences in their habitat choices. In addition to the three
      assemblage patterns, we found that niche size of the advanced termite family,
      Termitidae, was larger than that of the primitive termite families,
      Rhinotermitidae or Kalotermitidae. The broader choices of cellulosic materials as
      food sources may allow Termitidae to adapt to more diverse environments than
      exclusive wood feeders. Termite niche quantification could further be used to
      study termite pest adaption in urban areas, interspecific competition between
      native and invasive species, and plant decomposition processes. 

PMID- 26313960
TI  - Can Row Spacing Influence Arthropod Communities in Soybean? Implications for
      Early and Late Planting.
AB  - Row spacing in agricultural systems can influence crop yield as well as pest and
      predator abundances. Soybean (Glycine max L. Merrill) growers in Maryland
      typically plant in narrow (~19 cm), medium (~38 cm), or wide (~76 cm)-spaced
      rows, and there is a general lack of information on how these row-spacing schemes
      influence arthropod abundance and soybean yields. A study was conducted during
      two growing seasons to determine the effect of soybean row spacing and planting
      date (early and late) on soybean arthropods and yield. Despite a great deal of
      variation in arthropod responses to row spacing, and interactions between row
      spacing and study year, leaf-feeding herbivores were generally more abundant in
      narrow-spaced soybeans. All arthropod functional groups were more abundant, and
      yield was greater in early-planted soybeans relative to late-planted soybeans.
      Potential causes and implications of these finding are discussed.

PMID- 26313961
TI  - Differential Life History Trait Associations of Aphids with Nonpersistent Viruses
      in Cucurbits.
AB  - The diversity of vectors and fleeting nature of virus acquisition and
      transmission renders nonpersistent viruses a challenge to manage. We assessed the
      importance of noncolonizing versus colonizing vectors with a 2-yr survey of
      aphids and nonpersistent viruses on commercial pumpkin farms. We quantified aphid
      alightment using pan traps, while testing leaf samples with multiplex RT-PCR
      targeting cucumber mosaic virus (CMV), zucchini yellow mosaic virus (ZYMV),
      watermelon mosaic virus (WMV), and papaya ringspot virus (PRSV). Overall, we
      identified 53 aphid species (3,899 individuals), from which the melon aphid,
      Aphis gossypii Glover, a pumpkin-colonizing species, predominated (76 and 37% of
      samples in 2010 and 2011, respectively). CMV and ZYMV were not detected, but WMV
      and PRSV were prevalent, both regionally (WMV: 28/29 fields, PRSV: 21/29 fields)
      and within fields (infection rates = 69 and 55% for WMV in 2010 and 2011; 28 and
      25% for PRSV in 2010 and 2011). However, early-season samples showed extremely
      low infection levels, suggesting cucurbit viruses are not seed-transmitted and
      implicating aphid activity as a causal factor driving virus spread.
      Interestingly, neither noncolonizer and colonizer alightment nor total aphid
      alightment were good predictors of virus presence, but community analyses
      revealed species-specific relationships. For example, cowpea aphid (Aphis
      craccivora Koch) and spotted alfalfa aphid (Therioaphis trifolii Monell f.
      maculata) were associated with PRSV infection, whereas the oleander aphid (Aphis
      nerii Bover de Fonscolombe) was associated with WMV spread within fields. These
      outcomes highlight the need for tailored management plans targeting key vectors
      of nonpersistent viruses in agricultural systems.

PMID- 26313962
TI  - The Endosymbiont Arsenophonus Provides a General Benefit to Soybean Aphid
      (Hemiptera: Aphididae) Regardless of Host Plant Resistance (Rag).
AB  - Soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), invokes
      substantial chemical treatment and economic cost in North America. Resistant
      soybean genotypes hold promise as a low-impact control methodology, but soybean
      aphid "biotypes" capable of development on resistant soy cast doubt on the
      durability of soy resistance. We hypothesized that variation in soybean aphid
      ability to colonize resistant soy is partially attributable to a bacterial
      symbiont of soybean aphid, Arsenophonus. We used microinjection to manipulate
      Arsenophonus infection in both virulent and avirulent aphid biotypes, resulting
      in five pairs of infected versus uninfected isolines. These isolines were
      subjected to various population growth rate assays on resistant Rag versus
      susceptible soybean. We found that aphid virulence on Rag soybean was not
      dependent on Arsenophonus: virulent aphid biotypes performed well on Rag soybean,
      and avirulent aphid biotypes performed poorly on Rag soybean, regardless of
      whether Arsenophonus was present or not. However, we did find that Arsenophonus
      infected clones on average performed significantly better than their paired
      uninfected isolines. This pattern was not consistently evident on every date for
      every clone, either in the population assays nor when we compared lifetime
      fecundity of individual aphids in a separate experiment. Nevertheless, this
      overall benefit for infected aphids may be sufficient to explain the high
      frequency of Arsenophonus infection in soybean aphids. 

PMID- 26313963
TI  - Changes in Endosymbiotic Bacteria of Brown Planthoppers During the Process of
      Adaptation to Different Resistant Rice Varieties.
AB  - The specific primers of five species of endosymbiotic bacteria were designed to
      determine their numbers in three virulent populations of brown planthopper,
      Nilapavata lugens Stal, and to assess changes during adaptation to different
      resistant varieties using fluorescent quantitative PCR. The results showed that
      Chryseobacterium was the dominant bacteria in all three populations of brown
      planthopper, followed by Acinetobacter in TN1 population, Arsenophonus and
      Serratia in Mudgo population, and Arthrobacter and Acinetobacter in ASD7
      population. When the TN1 population of brown planthopper was transferred to ASD7
      (with resistant gene bph2) rice plants, Chryseobacterium was still the dominant
      bacteria, but the originally subdominant Acinetobacter declined to a level that
      was not significantly different from that of other endosymbiotic bacteria. After
      they were transferred to Mudgo (with resistant gene Bph1), Serratia and
      Arsenophonus increased significantly and became the dominant bacteria. However,
      they declined to a level that was not significantly different from that of the
      three other species after two generations. When ASD7 and Mudgo populations of
      brown planthopper were transferred to the susceptible variety TN1, the community
      of endosymbiotic bacteria in the ASD7 population of brown planthopper showed no
      significant changes. However, the numbers of Acinetobacter and Arthrobacter in
      the Mudgo population of brown planthopper exhibited a transient increase and
      returned to their original levels after two generations. After the Mudgo
      population of brown planthopper was transferred to ASD7 rice plants, the quantity
      of endosymbiotic bacteria fluctuated, but the bacterial structure did not change
      significantly. However, after the ASD7 population of brown planthopper was
      transferred to the Mudgo rice plants, the bacterial structure changed
      significantly. Serratia and Arsenophonus increased significantly and became
      dominant. Although Serratia and Arsenophonus decreased significantly after a
      generation, they were still greater than Chryseobacterium. It was presumed that
      Chryseobacterium was dominant in all three populations of virulent brown
      planthoppers, but had no significant effect on virulence variation of brown
      planthopper. However, Serratia and Arsenophonus might be correlated with
      virulence variation of brown planthopper. 

PMID- 26313964
TI  - Do Bacterial Symbionts Govern Aphid's Dropping Behavior?
AB  - Defensive symbiosis is amongst nature's most important interactions shaping the
      ecology and evolution of all partners involved. The pea aphid, Acyrthosiphon
      pisum Harris (Hemiptera: Aphididae), harbors one obligatory bacterial symbiont
      and up to seven different facultative symbionts, some of which are known to
      protect the aphid from pathogens, natural enemies, and other mortality factors.
      Pea aphids typically drop off the plant when a mammalian herbivore approaches it
      to avoid incidental predation. Here, we examined whether bacterial symbionts
      govern the pea aphid dropping behavior by comparing the bacterial fauna in
      dropping and nondropping aphids of two A. pisum populations, using two molecular
      techniques: high-throughput profiling of community structure using 16 S reads
      sequenced on the Illumina platform, and diagnostic polymerase chain reaction
      (PCR). We found that in addition to the obligatory symbiont, Buchnera aphidicola,
      the tested colonies of A. pisum harbored the facultative symbionts Serratia
      symbiotica, Regiella insecticola and Rickettsia, with no significant differences
      in infection proportions between dropping and nondropping aphids. While S.
      symbiotica was detected by both techniques, R. insecticola and Rickettsia could
      be detected only by diagnostic PCR. We therefore conclude that A. pisum's
      dropping behavior is not affected by its bacterial symbionts and is possibly
      affected by other factors.

PMID- 26313965
TI  - Effects of Host Plant on Development and Body Size of Three Haplotypes of
      Bactericera cockerelli (Hemiptera: Triozidae).
AB  - Potato psyllid, Bactericera cockerelli (Sulc) (Hemiptera: Triozidae), is an
      economic pest of solanaceous crops in North and Central America, and in New
      Zealand. Four genetic haplotypes of the psyllid have been identified in North
      America. Three of these haplotypes (Central, Western, and Northwestern) are
      common on potato crops within the major potato-growing regions of Idaho, Oregon,
      and Washington. Within this growing region, a weedy perennial nightshade, Solanum
      dulcamara (bittersweet nightshade), has been identified to be an important
      overwintering host and spring or summer source of psyllids colonizing potato
      fields. It is unclear whether bittersweet nightshade is a highly suitable host
      plant for all three haplotypes known to occur in the Pacific Northwest. The
      objective of the present study was to examine developmental traits and adult body
      size of all three haplotypes of psyllids reared on potato and bittersweet
      nightshade. Averaged over haplotype, development times were longer for psyllids
      reared on nightshade than potato. Duration of the preoviposition period, egg
      incubation requirements, nymphal development time, and total developmental time
      averaged 7.4, 5.9, 23.5, and 29.5 d on nightshade and 4.9, 5.5, 22.3, and 27.9 d
      on potato, respectively. The largest host effects were found for the Central
      haplotype, which exhibited a substantially extended (by over 5 d) preoviposition
      period on nightshade compared with potato. Averaged over host plant, nymphal and
      total development times of the Northwestern haplotype were longer (25.5 and 31.1
      d, respectively) than those of the Western and Central haplotypes. The
      Northwestern haplotype was largest in overall body size, while the Central
      haplotype had the smallest overall body size, irrespective of host plant. Both
      sexes exhibited this trend.

PMID- 26313966
TI  - Plant Photosynthetic Responses During Insect Effector-Triggered Plant
      Susceptibility and Immunity.
AB  - Gall-inducing insects are known for altering source-sink relationships within
      plants. Changes in photosynthesis may contribute to this phenomenon. We
      investigated photosynthetic responses in wheat [Triticum aestivum L. (Poaceae:
      Triticeae)] seedlings attacked by the Hessian fly [Mayetiola destructor (Say)
      (Diptera: Cecidomyiidae], which uses a salivary effector-based strategy to induce
      a gall nutritive tissue in susceptible plants. Resistant plants have surveillance
      systems mediated by products of Resistance (R) genes. Detection of a specific
      salivary effector triggers downstream responses that result in a resistance that
      kills neonate larvae. A 2 * 2 factorial design was used to study maximum leaf
      photosynthetic assimilation and stomatal conductance rates. The plant treatments
      were-resistant or susceptible wheat lines expressing or not expressing the H13
      resistance gene. The insect treatments were-no attack (control) or attack by
      larvae killed by H13 gene-mediated resistance. Photosynthesis was measured for
      the second and third leaves of the seedling, the latter being the only leaf
      directly attacked by larvae. We predicted effector-based attack would trigger
      increases in photosynthetic rates in susceptible but not resistant plants. For
      susceptible plants, attack was associated with increases (relative to controls)
      in photosynthesis for the third but not the second leaf. For resistant plants,
      attack was associated with increases in photosynthesis for both the second and
      third leaves. Mechanisms underlying the increases appeared to differ. Resistant
      plants exhibited responses suggesting altered source-sink relationships.
      Susceptible plants exhibited responses suggesting a mechanism other than altered
      source-sink relationships, possibly changes in water relations that contributed
      to increased stomatal conductance. 

PMID- 26313967
TI  - Increased Susceptibility to Aphids of Flowering Wheat Plants Exposed to Low
      Temperatures.
AB  - Frost is known to directly affect flowering wheat plants (Triticum aestivum L.)
      and lead to reduced grain yield. Additionally, it may increase wheat
      susceptibility to economically important pests, such as aphids (Hemiptera:
      Aphididae). Wheat plants at flowering stage were exposed to one of the three
      temperature treatments: ambient (11-12 degrees C), 0 degrees C, and -3 degrees C
      for 60 min. Preference (3-choice) and performance (no-choice) bioassays with
      aphids (Rhopalosiphum padi L.) were conducted 1, 3, 6, and 12 d after temperature
      treatments to assess effects of temperature-induced stress over time. As an
      initial feasibility study of using remote sensing technologies to detect frost
      induced stress in flowering wheat plants, hyperspectral imaging data were
      acquired from wheat plants used in preference bioassays. Element analysis of
      wheat plants was included to determine the effect of temperature-induced stress
      on the nutritional composition of flowering wheat plants. The results from this
      study support the following cause-effect scenario: a 60-min exposure to low
      temperatures caused a significant decrease in potassium and copper content of
      wheat plants 6 d after temperature exposure, and it coincided with a marked
      increase in preference by aphids of wheat plants. The preference exhibited by
      aphids correlated positively with performance of aphids, so the preference
      performance hypothesis was confirmed and possibly driven by potassium and copper
      content of wheat plants. In addition, we demonstrated that hyperspectral imaging
      data can be used to detect frost-induced susceptibility to aphid infestation in
      flowering wheat plants. These findings justify further research into airborne
      remote sensing of frost-induced stress and the possible secondary effects on crop
      susceptibility to arthropod pests. 

PMID- 26313968
TI  - Stylet Penetration Estimates for a Suite of Phytophagous Hemipteran Pests of Row
      Crops.
AB  - Members of the Miridae (Lygus lineolaris Palisot de Beauvois and Pseudatomoscelis
      seriatus Reuter) and Pentatomidae (Acrosternum hilare Say, Euschistus servus
      (Say), Euschistus tristigmus (Say), Euschistus quadrator Rolston, Oebalus pugnax
      (F.), Piezodorus guildinii (Westwood), and Thyanta custator accerra McAtee)
      comprise a piercing-sucking insect complex that continues to plague multiple
      crops, including cotton. All these species have been associated with pathogen
      transmission. Breaching of boll carpel walls facilitates introduction of
      pathogens, and it is unknown whether stylets of these pests can fully penetrate
      carpel walls. Thus, stylet penetration estimates are needed and have been the
      focus of the present work. Stylet penetration estimates for L. lineolaris were
      significantly deeper than P. seriatus. Among the Pentatomidae, highest mean
      penetration was estimated for E. servus followed by A. hilare, yet A. hilare
      possessed a longer rostrum. Similarly, O. pugnax showed deeper penetration
      estimates than P. guildinii yet P. guildinii possessed a longer rostrum. Thus,
      rostrum length should not be equated to penetration potential. Pseudatomoscelis
      seriatus and L. lineolaris both infest early-season cotton, and the ranges of
      observed penetration indicate these insects, as well as the Pentatomidae, can
      breach the walls of critical pinhead squares and smaller bolls. The insects
      addressed herein affect a myriad of crops globally, and penetration estimates
      allow identification of growth stages susceptible to feeding and disease
      transmission. 

PMID- 26313969
TI  - Domestication in Murtilla (Ugni molinae) Reduced Defensive Flavonol Levels but
      Increased Resistance Against a Native Herbivorous Insect.
AB  - Plant domestication can have negative consequences for defensive traits against
      herbivores, potentially reducing the levels of chemical defenses in plants and
      consequently their resistance against herbivores. We characterized and quantified
      the defensive flavonols from multiple cultivated ecotypes with wild ancestors of
      murtilla, Ugni molinae Turcz, an endemic plant from Chile, at different times of
      the year, and examined their effects on a native insect herbivore, Chilesia rudis
      Butler (Lepidoptera: Arctiidae). We hypothesized that domestication results in a
      decrease in flavonol levels in U. molinae plants, and that this negatively
      affected C. rudis performance and preference. Ethanolic extracts were made from
      leaves, stems, and fruit of murtilla plants for flavonol analysis. Flavonols
      identified were kaempferol, quercetin, rutin, and quercetin 3-D-beta-glucoside,
      the last two being the most abundant. More interestingly, we showed differences
      in flavonol composition between wild and cultivated U. molinae that persisted for
      most of the year. Relative amounts of all four flavonols were higher in wild U.
      molinae leaves; however, no differences were found in the stem and fruit between
      wild and cultivated plants. In choice and no-choice assays, C. rudis larvae
      gained more mass on, and consumed more leaf material of, wild as compared with
      cultivated U. molinae plants. Moreover, when applied to leaves, larvae ate more
      leaf material with increasing concentrations of each flavonol compound. Our study
      demonstrates that domestication in U. molinae reduced the amount of flavonols in
      leaves as well as the performance and preference of C. rudis, indicating that
      these compounds stimulate feeding of C. rudis. 

PMID- 26313970
TI  - Using the British National Collection of Asters to Compare the Attractiveness of
      228 Varieties to Flower-Visiting Insects.
AB  - Wildlife-friendly gardening practices can help conserve biodiversity in urban
      areas. These include growing ornamental plant varieties attractive to flower
      visiting insects. Because varieties vary greatly in attractiveness, there is a
      need to quantify it in order to give objective advice to gardeners. Here, we used
      the British national collection of asters to compare the attractiveness of
      varieties to flower-visiting insects. We counted and identified insects as they
      foraged on flowers in 228 varieties growing in discrete patches that flowered
      during the survey period, 14 September-20 October 2012. In each variety, we also
      determined the overall capitulum size, the central disc floret area, and the ray
      floret color (blue, red, purple, or white). We also scored attributes relevant to
      gardening: attractiveness to humans, ease of cultivation, and availability in the
      United Kingdom. There was great variation among varieties in their attractiveness
      to insects, ranging from 0.0 to 15.2 per count per square meter, and highly
      skewed, with most being unattractive. A similar skew held for the two main insect
      categories, honey bees and hover flies, which comprised 28 and 64% of all
      insects, respectively. None of the floral traits or attributes relevant to
      gardening correlated significantly with attractiveness to insects. Our study
      shows the practicality of using a national collection for quantifying and
      comparing the attractiveness of ornamental varieties to flower-visiting insects.
      These results imply that choosing varieties carefully is likely to be of
      conservation benefit to flower-visiting insects, and that doing so is a no-cost
      option in terms of garden beauty and workload. 

PMID- 26313971
TI  - Rhamnus cathartica (Rosales: Rhamnaceae) Invasion Reduces Ground-Dwelling Insect
      Abundance and Diversity in Northeast Iowa Forests.
AB  - European buckthorn (Rhamnus cathartica L.) is an invasive woody shrub in
      deciduous forests of the Upper Midwest. Studies have suggested buckthorn invasion
      has negative effects on native plants, soil, and ecosystems, but its impacts on
      insects are largely unstudied. To test the impact of buckthorn invasion on ground
      dwelling insects in forests of northeastern Iowa, pitfall traps were used to
      sample ground-dwelling insects at five sites four different periods from June to
      August 2013. Each site had three treatments: areas heavily infested with
      buckthorn, areas where buckthorn has not established, and areas where buckthorn
      had been removed within the past 2-10 yr. Most insects were identified to family
      and quantified; while ground beetles (Coleoptera: Carabidae) and ants
      (Hymenoptera: Formicidae) were identified to species and quantified. In total,
      11,576 insects representing eight orders and 46 families were collected. Areas
      uninvaded by buckthorn had significantly greater insect abundance and taxonomic
      richness than areas invaded by buckthorn. Of the 948 ground beetles representing
      40 species, abundance, species richness, and Shannon diversity indices were
      significantly lower in areas invaded by buckthorn compared with areas with no
      buckthorn. The 2,661 ants from 24 species had similar trends, but treatment
      differences were not significant because of high variability. These results
      clearly show a negative impact of buckthorn invasion on the abundance and
      taxonomic richness of ground-dwelling insects. 

PMID- 26313972
TI  - An Induced Susceptibility Response in Soybean Promotes Avirulent Aphis glycines
      (Hemiptera: Aphididae) Populations on Resistant Soybean.
AB  - Observations of virulent Aphis glycines Matsumura populations on resistant
      soybean in North America occurred prior to the commercial release of Rag genes.
      Laboratory assays confirmed the presence of four A. glycines biotypes in North
      America defined by their virulence to the Rag1 and Rag2 genes. Avirulent and
      virulent biotypes can co-occur and potentially interact on soybean, which may
      result in induced susceptibility. We conducted a series of experiments to
      determine if the survival of avirulent biotypes on susceptible and resistant
      soybean containing the Rag1 or Rag1 + Rag2 genes was affected by the presence of
      either avirulent or virulent conspecifics. Regardless of virulence to Rag genes,
      initial feeding by conspecifics increased the survival of subsequent A. glycines
      populations on both susceptible and resistant soybean. Avirulent populations
      increased at the same rate as virulent populations if the resistant plants were
      initially colonized with virulent aphids. These results are the first to
      demonstrate that virulent A. glycines increase the suitability of resistant
      soybean for avirulent conspecifics, thus explaining the lack of genetic
      differentiation observed in North America between A. glycines populations on
      resistant and susceptible soybean. These results suggest the occurrence of
      virulence toward Rag genes in North America may be overestimated. In addition
      this may alter the selection pressure for virulence genes to increase in a
      population. Therefore, insect resistance management models for A. glycines may
      need to incorporate induced susceptibility factors to determine the relative
      durability of resistance genes. 

PMID- 26313973
TI  - Population Dynamics of Frankliniella bispinosa (Thysanoptera: Thripidae) and the
      Predator Orius insidiosus (Hemiptera: Anthocoridae) as Influenced by Flower Color
      of Lagerstroemia (Lythraceae).
AB  - Crapemyrtle is a common landscape planting that is a resource subsidy for
      beneficial insects. Field studies were conducted to determine the influence of
      crapemyrtle flower color on the population abundances and predator-prey dynamics
      of the herbivorous Frankliniella species and the predator Orius insidiosus.
      Adults and immatures of predator and prey were highly anthophilous, preferring
      white 'Acoma' flowers compared with lavender 'Apalachee', red 'Carolina Beauty',
      and pink 'Choctaw'. The predator was aggregated with its prey in a density
      dependent manner: the adults by preferring the crapemyrtle clones also preferred
      by the thrips and the nymphs by direct tracking or as a function of increased
      prey and fecundity. Acoma was best for preference and buildup of O. insidiosus
      populations, and it was the only clone where there was no buildup in thrips
      populations. Two species of Karnyothrips (Thysanoptera: Phlaoethripidae),
      predators of small insects, were common in Tillandsia usneoides, an epiphyte on
      the crapemyrtle. Crapemyrtle is a bridge to enhance populations of O. insidiosus
      during summer months when there are few other hosts in the southern USA. 

PMID- 26313974
TI  - Substrate-Borne Marking in the Parasitoid Wasp Urolepis rufipes (Hymenoptera:
      Pteromalidae).
AB  - Many animals use pheromone marking as a way to identify their territory or other
      resources. Among insects, substrate-borne marking is frequently reported for
      females, which in many species make marks containing oviposition-deterring
      pheromone, which other females avoid. However, there are fewer reports of
      substrate-borne marking for males. Here, marking in males of the parasitoid wasp
      Urolepis rufipes (Ashmead) is described. The conditions under which males mark
      and whether males and females respond to the males' marks were examined using
      behavioral observations. Males marked by dragging the tips of their abdomens
      across a substrate. They marked much more after mating and after consuming honey.
      They also marked more when with a female, irrespective of copulation, although
      not when with a male. Females spent more time on or near marked substrates, and
      males also responded to their own marks. Although males aggressively and
      successfully defended areas that they had marked against other males, males did
      not respond to another male's marks in the conspecific's absence. In contrast to
      males, females did not mark, either on the surface of hosts or on other surfaces,
      and males showed no detectable response to surfaces which females had recently
      occupied. 

PMID- 26313975
TI  - Suitability of Bactrocera dorsalis (Diptera: Tephritidae) Pupae for Spalangia
      endius (Hymenoptera: Pteromalidae).
AB  - Spalangia endius (Walker) (Hymenoptera: Pteromalidae) is found to be one of the
      most important natural enemies of Bactrocera dorsalis Hendel (Diptera:
      Tephritidae) pupae in China. In this study, the influence of host pupal age on
      the preference for and suitability of the host by the parasitoid S. endius was
      determined using choice and nonchoice tests. S. endius females accepted the 1-7 d
      old B. dorsalis pupae for oviposition, and their offspring developed
      successfully. However, the S. endius preferentially parasitized the 2-, 3-, and 4
      d-old host pupae. The emergence rate of the adult progeny was not affected by the
      host pupal age, nor was the male body weight, male longevity, and sex ratio of
      the parasitoid offspring. However, the shortest development time of both male and
      female progeny and the greatest size and adult longevity of female progeny were
      observed in hosts that were <=4 d old. Females emerged later and lived longer
      than males, and they weighed more than the males. Host mortality decreased as the
      age of the host increased for 1-7-d-old hosts. Our findings suggest that 2-, 3-,
      and 4-d-old B. dorsalis pupae would be the best host ages at which to rear S.
      endius for effective control in field releases. 

PMID- 26313976
TI  - Field Estimates of Attraction of Ceratitis capitata to Trimedlure and Bactrocera
      dorsalis (Diptera: Tephritidae) to Methyl Eugenol in Varying Environments.
AB  - Measuring and modeling the attractiveness of semiochemical-baited traps is of
      significant importance to detection, delimitation, and control of invasive pests.
      Here, we describe the results of field mark-release-recapture experiments with
      Ceratitis capitata (Wiedemann) and Bactrocera dorsalis (Hendel) to estimate the
      relationship between distance from a trap baited with trimedlure and methyl
      eugenol, respectively, and probability of capture for a receptive male insect.
      Experiments were conducted using a grid of traps with a central release point at
      two sites on Hawaii Island, a Macadamia orchard on the East side of the island
      and a lava field on the West side. We found that for B. dorsalis and methyl
      eugenol there is a 65% probability of capture at ~36 m from a single trap,
      regardless of habitat. For C. capitata, we found a 65% probability of capture at
      a distance of ~14 m from a single trap in the orchard and 7 m in the lava field.
      We also present results on the spatial and temporal pattern of recaptures. The
      attraction data are analyzed via a hyperbolic secant-based capture probability
      model. 

PMID- 26313977
TI  - Multistate Comparison of Attractants for Monitoring Drosophila suzukii (Diptera:
      Drosophilidae) in Blueberries and Caneberries.
AB  - Drosophila suzukii Matsumara, also referred to as the spotted wing drosophila,
      has recently expanded its global range with significant consequences for its
      primary host crops: blueberries, blackberries, raspberries, cherries, and
      strawberries. D. suzukii populations can increase quickly, and their infestation
      is difficult to predict and prevent. The development of effective tools to detect
      D. suzukii presence in new areas, to time the beginning of activity within a
      crop, to track seasonal activity patterns, and to gauge the effectiveness of
      management efforts has been a key research goal. We compared the efficiency,
      selectivity, and relationship to fruit infestation of a range of commonly used
      homemade baits and a synthetic formulated lure across a wide range of
      environments in 10 locations throughout the United States. Several homemade baits
      were more efficient than apple cider vinegar, a commonly used standard, and a
      commercially formulated lure was, in some configurations and environments,
      comparable with the most effective homemade attractant as well as potentially
      more selective. All alternative attractants also captured flies between 1 and 2
      wk earlier than apple cider vinegar, and detected the presence of D. suzukii
      prior to the development of fruit infestation. Over half the Drosophila spp.
      flies captured in traps baited with any of the attractants were not D. suzukii,
      which may complicate their adoption by nonexpert users. The alternative D.
      suzukii attractants tested are improvement on apple cider vinegar and may be
      useful in the development of future synthetic lures. 

PMID- 26313978
TI  - Intraspecific Signals Inducing Aggregation in Periplaneta americana (Insecta:
      Dictyoptera).
AB  - Chemical communication is necessary to induce aggregation and to maintain the
      cohesion of aggregates in Periplaneta americana (L.) cockroaches. We aimed to
      identify the chemical message inducing aggregation in this species. Two types of
      bioassays were used-binary choice tests in Petri dishes and tests in Y
      olfactometer. Papers conditioned by direct contact of conspecifics induce
      aggregation when proposed in binary choice tests and were attractive in a Y
      olfactometer. The identification of the molecules present on these conditioned
      papers indicated that dichloromethane extracts contained mainly cuticular
      hydrocarbons whereas methanol extracts contained more volatile molecules. Only a
      mixture of extracts in both solvents induced aggregation. High concentrations of
      cuticular hydrocarbons are necessary to induce aggregation when presented alone.
      When presented with volatile molecules present in methanol extracts, low
      concentrations of cuticular hydrocarbons are sufficient to induce aggregation if
      they are presented in contact. Among volatile molecules collected on filter
      paper, a mixture of three compounds-hexadecanoic acid, pentadecanoic acid, and
      pentaethylene glycol-induced aggregation. Our results provide evidence that
      aggregation processes in P. americana relies on a dual mechanism: attraction over
      long distances by three volatile molecules and maintenance on site by contact
      with cuticular hydrocarbons. 

PMID- 26313979
TI  - Field Evaluation of Agrotis ipsilon (Lepidoptera: Noctuidae) Pheromone Blends and
      Their Application to Monitoring Moth Populations in China.
AB  - The attractiveness of a series of mixtures of (Z)-7-dodecenyl acetate (Z7-12:Ac),
      (Z)-9-tetradecenyl acetate (Z9-14:Ac), and (Z)-11-hexadecenyl acetate (Z11
      16:Ac), the Agrotis ipsilon (Hufnagel) (Lepidoptera: Noctuidae) pheromone, were
      evaluated in four locations in China. The ternary blend of Z7-12:Ac, Z9-14:Ac,
      and Z11-16:Ac was the complete pheromone blend for A. ipsilon and the ratio of Z7
      12:Ac and Z9-14:Ac was optimal at 3:1. The most attractive ratio of Z11-16:Ac to
      the other components depended on geographic location. The optimal ratio was 3:1:6
      in Yunnan and Shanxi, 3:1:2 in Sichuan and ranged from 3:1:2 to 3:1:12 in
      Shanghai, which differs significantly from the ratio of 3:1:16 in Japan. The dose
      of the blend in the pheromone lure influenced attractiveness to male moths and
      was related to the temperature in the test locations. Attractiveness of sugar
      acetic acid-baited and pheromone-baited traps to male and female moths was
      different before and after the start of flowering of the oilseed rape crop; large
      numbers of female moths were attracted to sugar-acetic acid traps before
      flowering but none after flowering had started. This was similar for male moths
      and there was no synergistic effect when sugar-acetic acid solutions and
      pheromone were used together. These studies suggest that pheromone trapping based
      on the blends of three components can be an effective tool to improve the
      efficiency of monitoring of this pest in China. 

PMID- 26313980
TI  - Effects of Pheromone Release Rate and Trap Placement on Trapping of Agrilus
      planipennis (Coleoptera: Buprestidae) in Canada.
AB  - The emerald ash borer, Agrilus planipennis Fairmaire (Coleoptera: Buprestidae),
      is a devastating insect pest in its introduced range. A trapping system that
      increases trap catches or detection rates in low-density populations would be
      beneficial for survey programs. Five trapping experiments were conducted to
      investigate factors influencing capture rates of male beetles on dark green traps
      baited with the A. planipennis pheromone, (3Z)-dodecen-12-olide ((3Z)-lactone),
      plus the green leaf volatile, (3Z)-hexenol. Low doses (0.001-1.0 mg) of (3Z)
      lactone + (3Z)-hexenol did not consistently increase captures of male A.
      planipennis. In other experiments, mean captures of males were significantly
      higher on traps baited with a moderate dose (3.0 mg/septum) of (3Z)-lactone +
      (3Z)-hexenol, compared with lower doses (0.001, 0.1, and 1.0 mg) or (3Z)-hexenol
      alone. Next, we demonstrated that addition of (3Z)-lactone to traps baited with
      (3Z)-hexenol resulted in significantly greater increases in male captures when
      pairs of traps were placed on the same tree, than when traps were placed on
      adjacent trees. Moreover, significantly more A. planipennis were captured on
      pheromone-baited traps placed in the southern versus northern aspect of the
      crown. These results highlight the importance of experimental set-up for
      elucidating lure treatment effects and also suggests the (3Z)-lactone may be more
      active at close range. Our findings increase our understanding of the pheromone
      ecology of this species and lend support toward the use of dark green traps
      baited with 3.0 mg (3Z)-lactone + (3Z)-hexenol deployed in the south aspect of
      the canopy for detection programs for this insect.

PMID- 26313981
TI  - Attraction of the Invasive Halyomorpha halys (Hemiptera: Pentatomidae) to Traps
      Baited with Semiochemical Stimuli Across the United States.
AB  - A recent identification of the two-component aggregation pheromone of the
      invasive stink bug species, Halyomorpha halys (Stal), in association with a
      synergist, has greatly improved the ability to accurately monitor the seasonal
      abundance and distribution of this destructive pest. We evaluated the attraction
      of H. halys to black pyramid traps baited with lures containing the pheromone
      alone, the synergist methyl (2E,4E,6Z)-decatrienoate (MDT) alone, and the two
      lures in combination. Traps were deployed around areas of agricultural production
      including fruit orchards, vegetables, ornamentals, or row crops in Delaware,
      Maryland, North Carolina, New Jersey, New York, Ohio, Oregon, Pennsylvania,
      Virginia, and West Virginia from mid-April to mid-October, 2012 and 2013. We
      confirmed that H. halys adults and nymphs are attracted to the aggregation
      pheromone season long, but that attraction is significantly increased with the
      addition of the synergist MDT. H. halys adults were detected in April with peak
      captures of overwintering adults in mid- to late May. The largest adult captures
      were late in the summer, typically in early September. Nymphal captures began in
      late May and continued season long. Total captures declined rapidly in autumn and
      ceased by mid-October. Captures were greatest at locations in the Eastern Inland
      region, followed by those in the Eastern Coastal Plain and Pacific Northwest.
      Importantly, regardless of location in the United States, all mobile life stages
      of H. halys consistently responded to the combination of H. halys aggregation
      pheromone and the synergist throughout the entire season, suggesting that these
      stimuli will be useful tools to monitor for H. halys in managed systems.

PMID- 26313982
TI  - Expansion of the Mexican Rice Borer (Lepidoptera: Crambidae) into Rice and
      Sugarcane in Louisiana.
AB  - The Mexican rice borer, Eoreuma loftini (Dyar) (Lepidoptera: Crambidae), is an
      invasive pest of sugarcane, Saccharum spp., rice, Oryza sativa L., and other
      graminaceous crops in the Gulf Coast region of the United States. Traps baited
      with E. loftini female sex pheromones were used to document establishment and
      distribution of E. loftini near sugarcane, rice, and noncrop hosts in seven
      southwest Louisiana parishes from 2009 to 2013. Additional field surveys
      documented larval infestations in commercial sugarcane and rice. After its
      initial detection in 2008, no E. loftini were detected in Louisiana in 2009 and
      only two adults were captured in 2010. Trapping documented range expansion into
      Cameron, Beauregard, and Jefferson Davis parishes in 2011 and Allen, Acadia, and
      Vermilion parishes in 2013. During the course of this study, E. loftini expanded
      its range eastward into Louisiana 120 km from the Texas border (~22 km/yr).
      Surveys of larval infestations provided the first record of E. loftini attacking
      rice and sugarcane in Louisiana. Infestations of E. loftini in rice planted
      without insecticidal seed treatments in Calcasieu Parish reached damaging levels.

PMID- 26313983
TI  - Nonrandom Distribution of Cabbage Aphids (Hemiptera: Aphididae) in Dryland Canola
      (Brassicales: Brassicaceae).
AB  - Characterization of spatial distribution patterns of pests in large-scale
      agricultural fields is important because these patterns affect the sampling
      effort needed to accurately detect and estimate their population density. In this
      study, we conducted experimental releases of alate cabbage aphids (Brevicoryne
      brassicae L.) into centers of small plots of canola (Brassica napus L.), and
      their gradual spread over a 7-wk period was characterized. The small-plot
      experiment demonstrated gradient effects from plot centers and a nonrandom
      vertical distribution, with initial colonization occurring on the abaxial side of
      lower canopy leaves and, later, highest numbers of cabbage aphids occurring on
      racemes. We also conducted large-scale distribution analyses of cabbage aphid
      infestations in two commercial canola fields, using visual inspection and sweep
      net sampling. We used canola plant phenological and landscape features as
      explanatory variables of the spatial distribution of cabbage aphid counts. These
      large-scale experiments showed strong edge effects with negative associations
      between cabbage aphid counts and distance to crop edges, including tree lines and
      contour banks. Cabbage aphid distribution was more effectively displayed using
      logistic regression than ordinary regression, Spatial Analysis by Distance
      IndicEs, or both. Based on the study findings, a nonrandom or optimized
      inspection approach is proposed to focus monitoring efforts on canola plants
      within 20 m from field edges with particular attention to the abaxial side of
      lower-canopy leaves. Detection of advanced cabbage aphid infestations should
      target the racemes within 20 m from field edges. 

PMID- 26313984
TI  - Sampling Methods for Detection and Monitoring of the Asian Citrus Psyllid
      (Hemiptera: Psyllidae).
AB  - The Asian citrus psyllid (ACP), Diaphorina citri Kuwayama is a key pest of citrus
      due to its role as vector of citrus greening disease or "huanglongbing." ACP
      monitoring is considered an indispensable tool for management of vector and
      disease. In the present study, datasets collected between 2009 and 2013 from 245
      citrus blocks were used to evaluate precision, sensitivity for detection, and
      efficiency of five sampling methods. The number of samples needed to reach a 0.25
      standard error-mean ratio was estimated using Taylor's power law and used to
      compare precision among sampling methods. Comparison of detection sensitivity and
      time expenditure (cost) between stem-tap and other sampling methodologies
      conducted consecutively at the same location were also assessed. Stem-tap
      sampling was the most efficient sampling method when ACP densities were moderate
      to high and served as the basis for comparison with all other methods. Protocols
      that grouped trees near randomly selected locations across the block were more
      efficient than sampling trees at random across the block. Sweep net sampling was
      similar to stem-taps in number of captures per sampled unit, but less precise at
      any ACP density. Yellow sticky traps were 14 times more sensitive than stem-taps
      but much more time consuming and thus less efficient except at very low
      population densities. Visual sampling was efficient for detecting and monitoring
      ACP at low densities. Suction sampling was time consuming and taxing but the most
      sensitive of all methods for detection of sparse populations. This information
      can be used to optimize ACP monitoring efforts. 

PMID- 26313985
TI  - Is Vector Control Sufficient to Limit Pathogen Spread in Vineyards?
AB  - Vector control is widely viewed as an integral part of disease management. Yet
      epidemiological theory suggests that the effectiveness of control programs at
      limiting pathogen spread depends on a variety of intrinsic and extrinsic aspects
      of a pathosystem. Moreover, control programs rarely evaluate whether reductions
      in vector density or activity translate into reduced disease prevalence. In areas
      of California invaded by the glassy-winged sharpshooter (Homalodisca vitripennis
      Germar), Pierce's disease management relies heavily on chemical control of this
      vector, primarily via systemic conventional insecticides (i.e., imidacloprid).
      But, data are lacking that attribute reduced vector pressure and pathogen spread
      to sharpshooter control. We surveyed 34 vineyards over successive years to assess
      the epidemiological value of within-vineyard chemical control. The results showed
      that imidacloprid reduced vector pressure without clear nontarget effects or
      secondary pest outbreaks. Effects on disease prevalence were more nuanced.
      Treatment history over the preceding 5 yr affected disease prevalence, with
      significantly more diseased vines in untreated compared with regularly or
      intermittently treated vineyards. Yet, the change in disease prevalence between
      years was low, with no significant effects of insecticide treatment or vector
      abundance. Collectively, the results suggest that within-vineyard applications of
      imidacloprid can reduce pathogen spread, but with benefits that may take multiple
      seasons to become apparent. The relatively modest effect of vector control on
      disease prevalence in this system may be attributable in part to the currently
      low regional sharpshooter population densities stemming from area-wide control,
      without which the need for within-vineyard vector control would be more
      pronounced.

PMID- 26313986
TI  - Effect of Spring and Winter Temperatures on Winter Moth (Geometridae:
      Lepidoptera) Larval Eclosion in the Northeastern United States.
AB  - Field and laboratory experiments were conducted to elucidate various factors
      influencing the temperature-dependent larval eclosion of winter moth, Operophtera
      brumata L, in New England. We found no difference in duration of the embryonic
      stage of eggs reared from larvae collected in Massachusetts (MA) and on Vancouver
      Island, British Columbia (BC), where winter temperatures are rarely below
      freezing. The number of growing degree days (GDD) required for larval eclosion
      declined with the number of days chilled in the laboratory and number of days
      below freezing in the field, confirming the findings of previous studies. Thus,
      eggs hatched with fewer GDD, when the spring came later than usual. Date of
      oviposition had no effect on date of hatch. Eggs laid by naturally occurring
      (feral) females hatched sooner, with lower GDD, than eggs from laboratory-reared
      females from MA and BC held on the same trees over the winter. South-facing eggs
      on the stems of trees hatched on average 1.6 days sooner than north-facing eggs.
      GDD calculated from bihourly measures of temperature were 15% greater than GDD
      estimates based on the average of daily maximum and minimum temperatures, as used
      by many GDD estimates made for online sources. Over two years, the mean GDD in 
      degrees C for hatch of feral eggs was 176.53 +/- 6.35 SE based on bihourly
      temperature measurements, a 1 January start date, and a 3.9 degrees C
      developmental threshold. This value varied markedly, however, between the two
      years.

PMID- 26313987
TI  - Temperature-Dependent Survival of Adult Lygus hesperus (Hemiptera: Miridae).
AB  - The western tarnished plant bug, Lygus hesperus Knight (Hemiptera: Miridae), is a
      key pest of many horticultural and agronomic crops in the western United States.
      Despite its well documented pest status, many aspects of the basic biology,
      including overwintering ecology, of L. hesperus are poorly understood. We
      examined the influence of eight constant temperatures from 10 to 35 degrees C on
      survival of nondiapausing adult L. hesperus held with or without food, and the
      consequences of exposure to an extended period at 10 degrees C on subsequent
      reproduction. Survival analyses indicated that, on average, fed insects tended to
      live longer than unfed insects, females lived longer than males, and the survival
      time decreased with increasing temperature. Nonlinear regressions indicated that
      median survival for insects grouped by gender and feeding status declined
      exponentially with increasing temperature. Survival functions for combinations of
      insect class (gender and feeding status) and temperature were adequately
      described by the respective two-parameter logistic functions. When adults were
      held for 9 d at 27 degrees C with food after a 33-d period at 10 degrees C either
      with or without food, no deleterious effects of prior starvation on propensity to
      mate or fecundity were demonstrated. These findings indicate that when
      temperatures are low, nondiapausing L. hesperus adults are capable of extended
      host-free survival with little or no impact on subsequent reproduction. Our
      findings suggest the current understanding of L. hesperus overwintering dynamics
      is incomplete. In addition, our results provide quantitative baseline information
      to facilitate more comprehensive investigation of the ecology of L. hesperus
      overwintering.

PMID- 26313988
TI  - The Termite Reticulitermes flavipes (Rhinotermitidae: Isoptera) Can Acquire
      Micronutrients from Soil.
AB  - Micronutrients are important for metabolic processes and structures in insects.
      How termites obtain micronutrients from the environment is not fully understood.
      It has been suggested that lower subterranean termites of Rhinotermitidae only
      gain their nutrients from their food sources. However, for subterranean termites,
      soil offers a potential source of micronutrients. This study tested the
      hypothesis that subterranean termites acquire micronutrients from the soil.
      Laboratory colonies of Reticulitermes flavipes Kollar were reared in arenas in
      which the levels of micronutrients, food, and soil were varied. The results
      showed that the micronutrients Ca (Calcium), Fe (Iron), Mg (Magnesium), and Mn
      (Manganese) were obtained from the soil, Cu (copper) was obtained by the food
      source, and K (Potassium) and Zn (Zinc) showed no differences between treatments.
      The results of this experiment suggest that subterranean termites can acquire
      micronutrients from the soil as well as other food sources. 

PMID- 26313989
TI  - Modeling the Effects of Constant and Variable Temperatures on the Vital Rates of
      an Age-, Stage-, and Sex-Structured Population by Means of the SANDY Approach.
AB  - We present a general and flexible mathematical model (called SANDY) that can be
      used to describe many biological phenomena, including the phenology of
      arthropods. In this paper, we demonstrate how the model can be fitted to vital
      rates (i.e., rates associated with development, survival, hatching, and
      oviposition) of the two-spotted spider mite (Tetranychus urticae (Koch)) exposed
      to different constant temperatures ranging from 15 degrees C to 37.5 degrees C.
      SANDY was incorporated into an age-, stage- and sex-structured dynamic model,
      which was fitted to cohort life-tables of T. urticae conducted at five constant
      temperatures (15, 20, 25, 30, and 35 degrees C). Age- and temperature-dependent
      vital rates for the three main stages (eggs, immatures, and adults) constituting
      the life-cycle of mites were adequately described by the SANDY model. The
      modeling approach allows for simulating the growth of a population in a variable
      environment. We compared the predicted net reproductive rate (R0) and intrinsic
      rate of natural increase (rm) at fluctuating temperatures with empirical values
      obtained from life-table experiments conducted at temperatures that changed with
      a daily amplitude (+/-0, +/-3, +/-6, +/-9, and +/-12 degrees C) around an average
      of 22 degrees C. Results show that R0 decreases with increasing amplitude, while
      rm is more robust to variable temperatures. An advantage of SANDY is that the
      same simple mathematical expression can be applied to describe all the vital
      rates. Besides, the approach is not confined to modeling the influence of a
      single factor on population growth but allows for incorporating the combined
      effect of several limiting factors, provided that the combined effect of the
      factors is multiplicative. 

PMID- 26313990
TI  - Resource Allocation to Flight in an Outbreaking Forest Defoliator Malacosoma
      disstria.
AB  - Allocation of larval nutrients affects adult life history traits in insects. This
      study assessed the effect of moth age and wing loading on flight capacity in an
      outbreaking forest lepidopteran, Malacosoma disstria Hubner . Insects were
      collected from high and low density populations after larval feeding, and flight
      capacity was tested directly with flight mills and indirectly through the
      allometric relationship between wing area and body size. Insects from these same
      populations collected as eggs and fed with a synthetic diet in the laboratory
      were tested in a separate experiment. Male moth propensity to fly increased with
      wing loading only when moths were collected as pupae after feeding in the field
      at high population densities. Moth age and wing loading did not affect the
      distance flown by male moths in any of the population density-nutrient regime
      combinations tested. Energy use increased with flight distance in both
      experiments. The slope of the allometric relationship between wing area and body
      mass did not differ from isometry when moths were collected as pupae after
      feeding at low and high population densities in the field. The slope of this
      relationship was steeper for males collected from high than low population
      densities. There was no allometric relationship between wing area and body mass
      of moths collected from these same populations as eggs and fed ad libitum in the
      laboratory as larvae. The results suggest that male M. disstria can allocate
      resources to different life history traits in response to differences in
      population density. 

PMID- 26313991
TI  - Reproductive Requirements and Life Cycle of Iberorhyzobius rondensis (Coleoptera:
      Coccinellidae), Potential Biological Control Agent of Matsucoccus feytaudi
      (Hemiptera: Matsucoccidae).
AB  - Several pine bast scales (Hemiptera: Matsucoccidae) are important pests of pine
      trees in the Northern Hemisphere. Some species are invasive and cause significant
      economic and environmental impacts. Such is the case with Matsucoccus feytaudi
      Ducasse, an invasive pest of maritime pine forests in Southeastern France, Italy,
      and Corsica. The ladybird Iberorhyzobius rondensis (Eizaguirre) is a recently
      described species that is endemic to the Iberian Peninsula and is a potential
      candidate for the biological control of M. feytaudi. However, little is known of
      the biology of I. rondensis. As part of the risk assessment study for a classical
      biological control program, the phenology and reproductive mechanisms of the
      beetle were analyzed. I. rondensis is univoltine and is seasonally synchronized
      with the phenology of the prey M. feytaudi, which is also univoltine. An
      obligatory reproductive diapause of 5-6 mo and the need to feed on the eggs of
      the prey to begin oviposition emerged as the two primary mechanisms that assure
      life cycle synchronization of the ladybird with its prey. Female fecundity was
      also higher when the ladybirds were fed M. feytaudi eggs. Life cycle
      synchronization with M. feytaudi and reproduction triggered by consumption of
      prey eggs indicate that I. rondensis is a promising biological control agent of
      the pine bast scale.

PMID- 26313992
TI  - Mechanism of Resistance Acquisition and Potential Associated Fitness Costs in
      Amyelois transitella (Lepidoptera: Pyralidae) Exposed to Pyrethroid Insecticides.
AB  - The polyphagous navel orangeworm, Amyelois transitella (Walker) (Lepidoptera:
      Pyralidae), is the most destructive pest of nut crops, including almonds and
      pistachios, in California orchards. Management of this insect has typically been
      a combination of cultural controls and insecticide use, with the latter
      increasing substantially along with the value of these commodities. Possibly
      associated with increased insecticide use, resistance has been observed recently
      in navel orangeworm populations in Kern County, California. In studies
      characterizing a putatively pyrethroid-resistant strain (R347) of navel
      orangeworm, susceptibility to bifenthrin and beta-cyfluthrin was compared with
      that of an established colony of susceptible navel orangeworm. Administration of
      piperonyl butoxide and S,S,S-tributyl phosphorotrithioate in first-instar feeding
      bioassays with the pyrethroids bifenthrin and beta-cyfluthrin produced
      synergistic effects and demonstrated that cytochrome P450 monooxygenases and
      carboxylesterases contribute to resistance in this population. Resistance is
      therefore primarily metabolic and likely the result of overexpression of specific
      cytochrome P450 monooxygenases and carboxylesterase genes. Resistance was
      assessed by median lethal concentration (LC50) assays and maintained across nine
      generations in the laboratory. Life history trait comparisons between the
      resistant strain and susceptible strain revealed significantly lower pupal
      weights in resistant individuals reared on the same wheat bran-based artificial
      diet across six generations. Time to second instar was greater in the resistant
      strain than the susceptible strain, although overall development time was not
      significantly different between strains. Resistance was heritable and may have an
      associated fitness cost, which could influence the dispersal and expansion of
      resistant populations in nut-growing areas in California. 

PMID- 26313993
TI  - Performance of Wild and Laboratory-Reared Gypsy Moth (Lepidoptera: Erebidae): A
      Comparison between Foliage and Artificial Diet.
AB  - The effects of long-term mass rearing of laboratory insects on ecologically
      relevant traits is an important consideration when applying research conclusions
      to wild populations or developing management strategies. Laboratory strains of
      the gypsy moth, Lymantria dispar (L.), an invasive forest pest in North America,
      have been continuously reared since 1967. Selection on these strains has enhanced
      a variety of traits, resulting in faster development, shorter diapause, and
      greater fecundity. As in many mass-reared insects, laboratory strains of the
      gypsy moth are also reared exclusively on artificial diets that lack much of the
      phytochemical and nutritional complexity associated with natural foliage. We
      tested for differences in growth and development of wild gypsy moth populations
      from across the invasive range in comparison to laboratory strains when reared on
      artificial diet and a preferred foliage host species, northern red oak (Quercus
      rubra L.). Overall, caterpillars reared on foliage had higher survival and faster
      development rates, with smaller differences among populations. When reared on
      artificial diet, laboratory strains had the highest performance as expected. The
      response from the wild populations was mixed, with two populations performing
      poorly on artificial diet and another performing nearly as well as the laboratory
      strains. Performance on diet was enhanced when larvae received cubed portions
      changed regularly, as opposed to filled cups. Understanding these relationships
      between food source and population performance is important for informing studies
      that examine population comparisons using wild and laboratory-reared strains. 

PMID- 26313994
TI  - The Influence of Weather and Lunar Phases on the Flight Activity of Paederus Rove
      Beetles (Coleoptera: Staphylinidae).
AB  - Despite the medical importance of Paederus beetles, no studies have studied the
      influence of the abiotic factors on the flight activity and nighttime dispersal
      of these insects in Brazil. Therefore, the influence of both climatic factors and
      moon phase on black-light catches of Paederus rove beetles was investigated.
      Paederus beetles were attracted to a black light source hourly from 1800 to 0600
      hours, and data on weather conditions as well as moon phase data were taken for
      every sampling date. Overall, 543 individuals of Paederus beetles belonging to
      four species were captured: P. protensus, P. columbinus, P. brasiliensis, and P.
      mutans. Paederus beetles were mostly active in the warmest parts of the studied
      nights. Variations in nighttime temperature, relative humidity, wind speed, cloud
      cover, and moon phases appear not to affect Paederus flight. The diurnal
      temperature was observed to affect the night hourly dispersal of Paederus rove
      beetles as well as their distribution pattern during the entire period of study.
      The true environmental condition responsible for Paederus beetles seasonal
      pattern and daily night dispersal in northeastern Brazil were the annual moisture
      and drought cycles and the diurnal maximum temperatures, respectively.
      Significant trap catches were observed in the earliest hours after sunset (1800
      2100), and people must be aware of this fact, as it can notably increase the risk
      of acquiring linearis dermatitis from the contact with large numbers of active
      Paederus. 

PMID- 26313995
TI  - Preference and Performance of Hippodamia convergens (Coleoptera: Coccinellidae)
      and Chrysoperla carnea (Neuroptera: Chrysopidae) on Brevicoryne brassicae,
      Lipaphis erysimi, and Myzus persicae (Hemiptera: Aphididae) from Winter-Adapted
      Canola.
AB  - In the southern plains of the United States, winter-adapted canola (Brassica
      napus L.) is a recently introduced annual oilseed crop that has rapidly increased
      in hectares during the past 10 yr. Winter canola fields are infested annually
      with populations of Brevicoryne brassicae (L.) and Lipaphis erysimi (Kaltenbach),
      and these Brassica specialists are known to sequester plant volatiles from host
      plants, producing a chemical defense system against predators. Myzus persicae
      (Sulzer) is also common in winter canola fields, but as a generalist herbivore,
      does not sequester plant compounds. These three aphid species are expected to
      affect predator survival and development in very different ways. We conducted
      laboratory studies to 1) determine whether Hippodamia convergens (Guerin
      Meneville) and Chrysoperla carnea (Stephens) larvae demonstrate feeding
      preferences among winter canola aphids and 2) describe the suitability of these
      prey species. Predators demonstrated no significant preference among prey, and
      each aphid species was suitable for predator survival to the adult stage.
      However, prey species significantly affected development times and adult weights
      of each predator species. Overall, predator development was delayed and surviving
      adults weighed less when provided with L. erysimi or B. brassicae, which
      sequestered high levels of indole glucosinolates from their host plants. Our
      results indicate that although common winter canola aphids were suitable prey for
      H. convergens and C. carnea, qualitative differences in nutritional suitability
      exist between Brassica-specialist aphids and the generalist M. persicae. These
      differences appear to be influenced by levels of sequestered plant compounds that
      are toxic to aphid predators. 

PMID- 26313996
TI  - Genetic Analysis of Termite Colonies in Wisconsin.
AB  - The objective of this study was to document current areas of subterranean termite
      activity in Wisconsin and to evaluate genetic characteristics of these northern,
      peripheral colonies. Here, amplified fragment-length polymorphism was used to
      characterize levels of inbreeding, expected heterozygosity, and percent
      polymorphism within colonies as well as genetic structure among populations
      sampled. Genetic analysis revealed two species of termites occur in Wisconsin,
      Reticulitermes flavipes (Kollar) and Reticulitermes tibialis Banks, both found in
      the southern half of the state. Colonies of both species in Wisconsin are thought
      to represent the northern boundary of their current distributions. Measurements
      of within colony genetic variation showed the proportion of polymorphic loci to
      be between 52.9-63.9% and expected heterozygosity to range from 0.122-0.189.
      Consistent with geographical isolation, strong intercolony genetic differences
      were observed, with over 50% of FST values above 0.25 and the remaining showing
      moderate levels of genetic differentiation. Combined with low levels of
      inbreeding in most collection locations (FIS 0.042-0.123), we hypothesize
      termites were introduced numerous times in the state, likely by anthropogenic
      means. We discuss the potential effects of these genetic characteristics on
      successful colony establishment of termites along the northern boundary compared
      with termites in the core region of their distribution. 

PMID- 26313997
TI  - Comparisons of Lygus lineolaris (Hemiptera: Miridae) Populations from Two
      Distinct Geographical Regions of Mississippi.
AB  - The tarnished plant bug, Lygus lineolaris (Palisot de Beauvois) (Hemiptera:
      Miridae), is a major pest of cotton (Gossypium hirsutum L.) in the state of
      Mississippi. Economic data indicate that L. lineolaris is a more serious pest of
      cotton in the Delta region of Mississippi than in the Hills region; however,
      little data exist comparing the two populations. Two experiments were undertaken
      to compare L. lineolaris from these two geographically distinct regions. In the
      first experiment, colonies of L. lineolaris from each region were reared in the
      laboratory under controlled conditions and measurements of development time,
      survivorship, fecundity, and hatch rate were compared. The geographic region of
      origin had no effect on any of the variables measured; however, the diet used for
      rearing had a significant effect on all variables except hatch rate. In the
      second experiment, part of the cox1 gene of the L. lineolaris mitochondrial
      genome was compared between the two populations to examine possible genetic
      differences between L. lineolaris from the two regions of Mississippi. Data
      revealed two cox1 clades in the Delta region and only one cox1 clade in the Hills
      region. Taken together, the data do not explain the reason for the differences in
      the severity of damage to cotton in the two regions. 

PMID- 26313998
TI  - Genetic Record for a Recent Invasion of Phenacoccus solenopsis (Hemiptera:
      Pseudococcidae) in Asia.
AB  - The cotton mealybug Phenacoccus solenopsis Tinsley is an emerging invasive insect
      pest. Since its first report as a pest in the United States in 1991, it has
      invaded and colonized more than 23 countries over the past century. It was first
      recorded from Pakistan in 2006 and from China in 2008. In this study, we
      performed field surveys from 2010 to 2012 and obtained mtCOI sequences from
      specimens across China and Pakistan, then compared them with already available
      mtCOI sequences from additional Asian and North American countries. Our genetic
      analysis provides evidence that P. solenopsis should be classified into two
      groups, one of which is found only in the United States, and the other found only
      in Asia. The Asian group contains nine unique haplotypes, two of which have
      invaded and spread across China, Pakistan, India, and Vietnam over the last 4-6
      yr. Our genetic analysis also indicates that P. solenopsis has a close
      relationship with the parasitoid wasp Aenasius bambawalei Hayat, providing
      preliminary evidence of a congruent spread of this mealybug and its parasitoids
      across China.

PMID- 26313999
TI  - Erratum.

PMID- 26314000
TI  - Erratum.

PMID- 26314006
TI  - Monitoring the Diversity of Hunting Ants (Hymenoptera: Formicidae) on a
      Fragmented and Restored Andean Landscape.
AB  - Hunting ants are predators of organisms belonging to different trophic levels.
      Their presence, abundance, and diversity may reflect the diversity of other ants
      and contribute to evaluate habitat conditions. Between 2003 and 2005 the
      restoration of seven corridors in an Andean rural landscape of Colombia was
      performed. The restoration took place in lands that were formerly either forestry
      plantations or pasturelands. To evaluate restoration progress, hunting ants were
      intensely sampled for 7 yr, using sifted leaf litter and mini-Winkler, and
      pitfall traps in 21 plots classified into five vegetation types: forests,
      riparian forests, two types of restored corridors, and pasturelands. The ant
      communities were faithful to their habitat over time, and the main differences in
      ant composition, abundance, and richness were due to differences among land use
      types. The forests and riparian forests support 45% of the species in the
      landscape while the restored corridors contain between 8.3-25%. The change from
      forest to pasturelands represents a loss of 80% of the species. Ant composition
      in restored corridors was significantly different than in forests but restored
      corridors of soil of forestry plantations retained 16.7% more species than
      restored corridors from pasturelands. Ubiquitous hunting ants, Hypoponera opacior
      (Forel) and Gnamptogenys ca andina were usually associated with pastures and
      dominate restored corridors. Other cryptic, small, and specialized hunting ants
      are not present in the restored corridors. Results suggest that the history of
      land use is important for the biodiversity of hunting ants but also that
      corridors have not yet effectively contributed toward conservation goals. 

PMID- 26314007
TI  - The Influence of Vegetation and Landscape Structural Connectivity on Butterflies
      (Lepidoptera: Papilionoidea and Hesperiidae), Carabids (Coleoptera: Carabidae),
      Syrphids (Diptera: Syrphidae), and Sawflies (Hymenoptera: Symphyta) in Northern
      Italy Farmland.
AB  - Landscape structure as well as local vegetation influence biodiversity in
      agroecosystems. A study was performed to evaluate the effect of floristic
      diversity, vegetation patterns, and landscape structural connectivity on
      butterflies (Lepidoptera: Papilionoidea and Hesperiidae), carabids (Coleoptera:
      Carabidae), syrphids (Diptera: Syrphidae), and sawflies (Hymenoptera: Symphyta).
      Vegetation analysis and insect samplings were carried out in nine sites within an
      intensively farmed landscape in northern Italy. Plant species richness and the
      percentage of tree, shrub, and herb cover were determined by means of the
      phytosociological method of Braun-Blanquet. Landscape structural connectivity was
      measured as the total length of hedgerow network (LHN) in a radius of 500 m
      around the center of each sampling transect. Butterflies species richness and
      abundance were positively associated both to herb cover and to plant species
      richness, but responded negatively to tree and shrub cover. Shrub cover was
      strictly correlated to both species richness and activity density of carabids.
      The species richness of syrphids was positively influenced by herb cover and
      plant richness, whereas their abundance was dependent on ligneous vegetation and
      LHN. Rarefaction analysis revealed that sawfly sampling was not robust and no
      relationship could be drawn with either vegetation parameters or structural
      connectivity. The specific responses of each insect group to the environmental
      factors should be considered in order to refine and optimize landscape management
      interventions targeting specific conservation endpoints. 

PMID- 26314008
TI  - Electrophysiological and Behavioral Responses of Chrysopa phyllochroma
      (Neuroptera: Chrysopidae) to Plant Volatiles.
AB  - The lacewing Chrysopa phyllochroma Waesmael is a polyphagous predator of many
      pests. Releasing lacewings is an important component of biological control
      programs, but it is difficult to establish populations on field crops.
      Electrophysiological and behavioral responses to 10 common plant volatiles were
      recorded to screen for lacewing-attracting compounds. Electroantennographic
      assays indicated that all of the tested compounds elicited responses from C.
      phyllochroma. Three green-leaf volatiles-(E)-2-hexenal, (Z)-3-hexenyl acetate,
      and (Z)-3-hexenol-produced the strongest responses. Weaker responses were
      observed to six terpenes-ocimene, linalool, (3E)-4,8-dimethyl-1,3,7-nonatriene,
      (E,E)-alpha-farnesene, limonene, and nerolidol-and to methyl salicylate. Using a
      Y-tube olfactometer, the behavioral assays of the eight most active compounds
      demonstrated that four-(Z)-3-hexenyl acetate, (Z)-3-hexenol, (3E)-4,8-dimethyl
      1,3,7-nonatriene, and linalool-were significant attractants for C. phyllochroma
      at specific concentrations. Three common plant volatile compounds-(Z)-3-hexenyl
      acetate, (3E)-4,8-dimethyl-1,3,7-nonatriene, and linalool-were also found to
      significantly enhance female ovipositing, resulting in a concentration of eggs.
      These observations are important for lacewing release as a pest control measure
      because they suggest means for retaining individuals and establishing populations
      using common plant volatiles. 

PMID- 26314009
TI  - Severe White Pine Blister Rust Infection in Whitebark Pine Alters Mountain Pine
      Beetle (Coleoptera: Curculionidae) Attack Density, Emergence Rate, and Body Size.
AB  - Exotic tree pathogens can cause devastating ecological effects on forests that
      can be exacerbated when infections increase the likelihood of attack by insects.
      Current high rates of mortality of whitebark pine (Pinus albicaulis Engelm.) are
      due to white pine blister rust caused by the exotic fungus, Cronartium ribicola
      J.C. Fisch, and the native mountain pine beetle (Dendroctonus ponderosae
      Hopkins). These two mortality agents interact in whitebark pine; mountain pine
      beetle preferentially selects white pine blister rust-infected whitebark pine
      over healthy trees, and likelihood of attack has been observed to increase with
      infection severity. We examined attack and emergence rates, and size and sex
      ratio of mountain pine beetle in whitebark pines exhibiting varying white pine
      blister rust infection severities. Mountain pine beetle attack density was lowest
      on the most severely infected trees, but emergence rates and size of beetles from
      these trees were greater than those from uninfected and less severely infected
      trees. Low attack rates on severely infected whitebark pine may indicate these
      trees have lower defenses and that fewer beetle attacks are needed to kill them.
      Higher beetle emergence rates from severely infected trees may be due to low
      intraspecific competition resulting from low attack rates or differences in
      nutrient quality. 

PMID- 26314010
TI  - Effect of Lures and Colors on Capture of Lady Beetles (Coleoptera: Coccinellidae)
      in Tedders Pyramidal Traps.
AB  - Purposeful attraction and aggregation of adult Coccinellidae at target sites
      would be useful for sampling purposes and pest suppression. We field-tested 1)
      lures in yellow and black pyramidal traps and 2) pyramidal traps that had been
      painted one or two colors (without lures) to determine if lures or trap color
      affected capture of adult Coccinellidae. In only one experiment with lures did a
      single rate of limonene increase trap capture, whereas no other lure ever did.
      Yellow traps, regardless of using a lure, always captured significantly more lady
      beetles than black traps. When single-color red, orange, yellow, green, blue,
      purple, black, and white traps (without lures) were tested, yellow traps captured
      significantly more lady beetles. Of all species of Coccinellidae captured in
      these single-color traps, 95% were the exotic species Harmonia axyridis (Pallas)
      and Coccinella septempunctata L. H. axyridis alone dominated trap capture
      comprising 74.1% of all lady beetles. Two-color traps (yellow-green, yellow
      orange, yellow-white, and yellow-black) never captured more than single-color
      yellow traps. These results demonstrate that yellow pyramidal traps can be used
      to purposefully attract, and when used without a collection device, possibly
      aggregate adult Coccinellidae at targeted field sites. 

PMID- 26314011
TI  - Postfire Succession of Ants (Hymenoptera: Formicidae) Nesting in Dead Wood of
      Northern Boreal Forest.
AB  - Dead wood decomposition begins immediately after tree death and involves a large
      array of invertebrates. Ecological successions are still poorly known for
      saproxylic organisms, particularly in boreal forests. We investigated the use of
      dead wood as nesting sites for ants along a 60-yr postfire chronosequence in
      northeastern coniferous forests. We sampled a total of 1,625 pieces of dead wood,
      in which 263 ant nests were found. Overall, ant abundance increased during the
      first 30 yr after wildfire, and then declined. Leptothorax cf. canadensis
      Provancher, the most abundant species in our study, was absent during the first 2
      yr postfire, but increased steadily until 30 yr after fire, whereas Myrmica
      alaskensis Wheeler, second in abundance, was found at all stages of succession in
      the chronosequence. Six other species were less frequently found, among which
      Camponotus herculeanus (Linne), Formica neorufibarbis Emery, and Formica aserva
      Forel were locally abundant, but more scarcely distributed. Dead wood lying on
      the ground and showing numerous woodborer holes had a higher probability of being
      colonized by ants. The C:N ratio was lower for dead wood colonized by ants than
      for noncolonized dead wood, showing that the continuous occupation of dead wood
      by ants influences the carbon and nitrogen dynamics of dead wood after wildfire
      in northern boreal forests. 

PMID- 26314013
TI  - An Evaluation of Butterfly Gardens for Restoring Habitat for the Monarch
      Butterfly (Lepidoptera: Danaidae).
AB  - The eastern migratory monarch butterfly (Danaus plexippus L.) population in North
      America hit record low numbers during the 2013-2014 overwintering season,
      prompting pleas by scientists and conservation groups to plant the butterfly's
      milkweed host plants (Asclepias spp.) in residential areas. While planting
      butterfly gardens with host plants seems like an intuitive action, no previous
      study has directly compared larval survival in gardens and natural areas to
      demonstrate that gardens are suitable habitats for Lepidoptera. In this study,
      milkweed was planted in residential gardens and natural areas. In 2009 and 2010,
      plants were monitored for oviposition by monarch butterflies and survival of
      monarch eggs and caterpillars. Monarchs oviposited significantly more frequently
      in gardens than in natural sites, with 2.0 and 6.2 times more eggs per plant per
      observation in 2009 and 2010, respectively. There were no significant differences
      in overall subadult survival between gardens and natural areas. Significant
      differences in survival were measured for egg and larval cohorts when analyzed
      separately, but these were not consistent between years. These results suggest
      that planting gardens with suitable larval host plants can be an effective tool
      for restoring habitat for monarch butterflies. If planted over a large area,
      garden plantings may be useful as a partial mitigation for dramatic loss of
      monarch habitat in agricultural settings. 

PMID- 26314012
TI  - The Effects of Restoration Age and Prescribed Burns on Grassland Ant Community
      Structure.
AB  - North American grassland environments are endangered as a result of degradation
      and conversion for agriculture and housing. Efforts to manage and restore
      grasslands have traditionally focused on monitoring plant communities to
      determine restoration success, but the incorporation of animal communities may
      provide important benchmarks of ecosystem function and restoration. Ants play
      many roles in maintaining ecosystem health in temperate grasslands, but
      relatively little is known about how ant communities respond to restoration. We
      studied the role that restoration age and prescribed burns have on ant
      communities in two types of Illinois grasslands, prairies and savannas, and
      identify indicator species of restoration success. Grassland environments
      included remnants and restorations that varied in age from newly restored sites,
      to sites that have been under restoration for >15 yr. We demonstrate that prairie
      and savanna ant communities are distinct, but respond to restoration in a similar
      manner. Three distinct prairie ant assemblages were identified based on the age
      of restoration of a site-sites <3 yr old, sites that have been under restoration
      >5 yr, and remnant prairies. Four distinct savanna ant assemblages were
      identified based on the age of restoration of a site-sites <3 yr old, sites 5-15
      yr old, sites >15 yr old, and remnant savanna environments. After accounting for
      restoration age, time since last burn in both prairie and savannas does not
      explain community composition or species richness. Several ant species in both
      prairies and savannas have predictable changes in incidence that indicate their
      suitability for use as indicator species.

PMID- 26314014
TI  - Incidence of Infestation and Larval Success of Emerald Ash Borer (Agrilus
      planipennis) on White Fringetree (Chionanthus virginicus), Chinese Fringetree
      (Chionanthus retusus), and Devilwood (Osmanthus americanus).
AB  - We compared the incidence of infestation by emerald ash borer (EAB) and lilac
      borer on white fringetree to that of its Asian congener, Chinese fringetree,
      Chionanthus retusus, and a North American relative, devilwood, Osmanthus
      americanus. We also conducted laboratory bioassays to determine the suitability
      of these hosts for EAB larvae. At Spring Grove Cemetery and Arboretum in
      Cincinnati, Ohio, 9 of 28 white fringetrees examined were infested by EAB. Most
      of the white fringetrees had lilac borer infestation, and most of the trees
      infested by EAB also had lilac borer infestation. None of the 11 Chinese
      fringetrees examined were infested by either EAB or lilac borer. Each of the five
      devilwood individuals examined was infested by lilac borer, but not EAB. At The
      Morton Arboretum in Lisle, Illinois, 7 of 16 white fringetrees examined were
      infested by EAB, while none of the seven Chinese fringetrees examined were
      infested by either insect. A 40-d bioassay confirmed that white fringetree was an
      acceptable host, producing fourth-instar larvae that were smaller than those
      produced on a highly susceptible cultivar of green ash, Fraxinus pennsylvanica.
      No larvae survived on Chinese fringetree, and neonates were largely incapable of
      feeding on it. Two larvae survived on devilwood, reaching the second instar and
      excavating extensive galleries. Future work should be aimed at biotic and abiotic
      factors influencing the susceptibility of white fringetree, as well as further
      examination of close relatives for their vulnerability to EAB. 

PMID- 26314015
TI  - Relations Between the Structure of Benthic Macro-Invertebrates and the
      Composition of Adult Water Beetle Diets from the Dytiscidae Family.
AB  - This paper investigates the relations between the diet structure of predaceous
      adult water beetles from the Dytiscidae family and the structure of macrofauna
      inhabiting the same environments. The field studies were carried out from April
      until September in 2012 and 2013 in 1-mo intervals. In total, >1,000 water
      beetles and 5,115 benthic macro-invertebrates were collected during the whole
      period of the study. Subsequently, 784 specimens of adult water beetles (70.6%
      out of the total sampled) with benthic macro-invertebrates found in their
      proventriculi, were subject to analysis. The predators were divided into three
      categories depending on their body size: small beetles (2.3-5.0 mm), medium-sized
      beetles (13-15 mm), and large beetles (27-37 mm). All adult Dytiscidae consumed
      primarily Ephemeroptera and Chironomidae larvae. Although Asellidae were
      numerically dominant inhabitants of the sites, the adult water beetles did not
      feed on them. The analysis of feeding relations between predators and their prey
      revealed that abundance of Ephemeroptera, Chironomidae, and larval Dytiscidae
      between the environment and the diet of adult Dytiscidae were strongly
      correlated. 

PMID- 26314016
TI  - Phylogenetic Relationships of the Symbiotic Bacteria in the Aphid Sitobion avenae
      (Hemiptera: Aphididae).
AB  - Aphids have developed symbiotic associations with different bacterial species,
      and some morphological and molecular analyses have provided evidence of the host
      relationship between the primary symbiotic bacteria (Buchnera aphidicola) and the
      aphid while the contrary with the secondary symbiotic bacteria. In this study, we
      investigated the phylogenetic relationships of the bacterial endosymbionts in the
      aphid Sitobion avenae (F.). We characterized all bacterial endosymbionts in 10
      genetically defined S. avenae clones by denaturing gradient gel electrophoresis
      and, from these clones, sequenced the 16S rRNA genes of both the primary
      endosymbiont, B. aphidicola (for the first time), and the secondary
      endosymbionts, Regiella insecticola and Hamiltonella defensa (for the first
      time). The phylogenetic analysis indicated that Buchnera from Sitobion related to
      those in Macrosiphoni. The analysis of the secondary endosymbionts indicated that
      there is no host relationship between H. defensa and R. insecticola from Sitobion
      and those from other aphid species. In this study, therefore, we identified
      further evidence for the relationship between Buchnera and its host and reported
      a relationship within the secondary endosymbionts of S. avenae from the same
      country, even though there were no relationships between the secondary bacteria
      and their host. We also discussed the diversity within the symbiotic bacteria in
      S. avenae clones. 

PMID- 26314017
TI  - Preferential Use of Carbon Sources in Culturable Aerobic Mesophilic Bacteria of
      Coptotermes curvignathus's (Isoptera: Rhinotermitidae) Gut and Its Foraging Area.
AB  - The lower termite, Coptotermes curvignathus, is one of the most prominent
      plantation pests that feed upon, digest, and receive nourishment from exclusive
      lignocellulose diets. The objective of this study was to examine the utilization
      of sole carbon sources by isolated culturable aerobic bacteria among communities
      from the gut and foraging pathway of C. curvignathus. We study the bacteria
      occurrence from the gut of C. curvignathus and its surrounding feeding area by
      comparing the obtained phenotypic fingerprint with Biolog's extensive species
      library. A total of 24 bacteria have been identified mainly from the family
      Enterobacteriaceae from the identification of Biolog Gen III. Overall, the
      bacteria species in the termite gut differ from those of foraging pathway within
      a location, except Acintobacter baumannii, which was the only bacteria species
      found in both habitats. Although termites from a different study area do not have
      the same species of bacteria in the gut, they do have a bacterial community with
      similar role in degrading certain carbon sources. Sugars were preferential in
      termite gut isolates, while nitrogen carbon sources were preferential in foraging
      pathway isolates. The preferential use of specific carbon sources by these two
      bacterial communities reflects the role of bacteria for regulation of carbon
      metabolism in the termite gut and foraging pathway. 

PMID- 26314018
TI  - A Binary Host Plant Volatile Lure Combined With Acetic Acid to Monitor Codling
      Moth (Lepidoptera: Tortricidae).
AB  - Field studies were conducted in the United States, Hungary, and New Zealand to
      evaluate the effectiveness of septa lures loaded with ethyl (E,Z)-2,4
      decadienoate (pear ester) and (E)-4,8-dimethyl-1,3,7-nonatriene (nonatriene)
      alone and in combination with an acetic acid co-lure for both sexes of codling
      moth, Cydia pomonella (L.). Additional studies were conducted to evaluate these
      host plant volatiles and acetic acid in combination with the sex pheromone, (E,E)
      8,10-dodecadien-1-ol (codlemone). Traps baited with pear ester/nonatriene +
      acetic acid placed within orchards treated either with codlemone dispensers or
      left untreated caught significantly more males, females, and total moths than
      similar traps baited with pear ester + acetic acid in some assays. Similarly,
      traps baited with codlemone/pear ester/nonatriene + acetic acid caught
      significantly greater numbers of moths than traps with codlemone/pear ester +
      acetic acid lures in some assays in orchards treated with combinational
      dispensers (dispensers loaded with codlemone/pear ester). These data suggest that
      monitoring of codling moth can be marginally improved in orchards under variable
      management plans using a binary host plant volatile lure in combination with
      codlemone and acetic acid. These results are likely to be most significant in
      orchards treated with combinational dispensers. Significant increases in the
      catch of female codling moths in traps with the binary host plant volatile blend
      plus acetic acid should be useful in developing more effective mass trapping
      strategies. 

PMID- 26314019
TI  - Microsatellite Variation of two Pacific Coast Drosophila suzukii (Diptera:
      Drosophilidae) Populations.
AB  - The vinegar fly, Drosophila suzukii (Diptera: Drosophilidae), is a recent invader
      in North America that has become a serious threat to small fruit production. It
      was first detected in California in 2008 and in Washington state in 2009. In this
      study, D. suzukii populations from the area of the original detection on
      California's central coast and from eastern Washington, the United States, were
      sampled over a 3-year period to determine genetic variation in both using
      microsatellite markers. Six different loci were successfully amplified and
      included in the analysis. These loci included nanos, elf1, antennapedia,
      mastermind, z600, and tenA. The population from eastern Washington was highly
      monomorphic with one locus, mastermind, having multiple alleles. There was
      greater genetic variation in the coastal California population with all loci
      having multiple alleles, with the exception of tenA. Owing to the relatively low
      levels of genetic variation in the eastern Washington population compared with
      the coastal California population, it appears that the D. suzukii population in
      the eastern Washington region has undergone a significant bottleneck. 

PMID- 26314020
TI  - Induced Effects on Red Imported Fire Ant (Hymenoptera: Formicidae) Forager Size
      Ratios by Pseudacteon spp. (Diptera: Phoridae): Implications on Bait Size
      Selection.
AB  - Red imported fire ants, Solenopsis invicta Buren, are adversely affected by
      phorid flies in the genus Pseudacteon by instigating defensive behaviors in their
      hosts, and in turn reducing the efficiency of S. invicta foraging. Multiple
      Pseudacteon species have been released in Texas, and research has been focused on
      the establishment and spread of these introduced biological control agents. Field
      experiments were conducted to determine bait particle size selection of S.
      invicta when exposed to phorid populations. Four different particle sizes of two
      candidate baits were offered to foragers (one provided by a pesticide
      manufacturer, and a laboratory-created bait). Foragers selectively were attracted
      to, and removed more 1-1.4-mm particles than any other bait size. The industry
      provided bait is primarily made of particles in the 1.4-2.0 mm size, larger than
      what was selected by the ants in this study. While there was a preference for
      foragers to be attracted to and rest on the industry-provided blank bait, S.
      invicta removed more of the laboratory-created bait from the test vials. There
      was an abundance of workers with head widths ranging from 0.5-0.75 mm collected
      from baits. This was dissimilar from a previous study wherein phorid flies were
      not active and in which large workers were collected in higher abundance at the
      site. This implies that phorid fly activity caused a shift for red imported fire
      ant colonies to have fewer large foragers.

PMID- 26314021
TI  - Synergistic Trap Response of the False Stable Fly and Little House Fly (Diptera:
      Muscidae) to Acetic Acid and Ethanol, Two Principal Sugar Fermentation Volatiles.
AB  - In an initial observation, large numbers of muscoid flies (Diptera) were captured
      as nontarget insects in traps baited with solutions of acetic acid plus ethanol.
      In subsequent field experiments, numbers of false stable fly Muscina stabulans
      (Fallen) and little house fly Fannia canicularis (L.) trapped with the
      combination of acetic acid plus ethanol were significantly higher than those
      trapped with either chemical alone, or in unbaited traps. Flies were trapped with
      acetic acid and ethanol that had been formulated in the water of the drowning
      solution of the trap, or dispensed from polypropylene vials with holes in the
      vial lids for diffusion of evaporated chemical. Numbers of both species of fly
      captured were greater with acetic acid and ethanol in glass McPhail traps,
      compared to four other similar wet trap designs. This combination of chemicals
      may be useful as an inexpensive and not unpleasant lure for monitoring or
      removing these two pest fly species. 

PMID- 26314022
TI  - Comparison of the Olfactory Preferences of Four of Filth Fly Pupal Parasitoid
      Species (Hymenoptera: Pteromalidae) for Hosts in Equine and Bovine Manure.
AB  - House flies (Musca domestica L.) and stable flies (Stomoxys calcitrans (L.))
      (Diptera: Muscidae) are common pests in equine and cattle facilities. Pupal
      parasitoids, primarily in the genera Spalangia and Muscidifurax (Hymenoptera:
      Pteromalidae), can be purchased for biological control of these flies. However,
      little is known about the host-habitat preferences associated with host-seeking
      by these parasitoids. The preferences of two Spalangia and two Muscidifurax
      species to odors associated with house fly hosts in equine and bovine manure were
      investigated in the laboratory using a Y-tube olfactometer. Odor stimuli from
      manure without developing flies, third-instar house flies in manure, and fly host
      puparia in manure were evaluated. In choice tests, S. cameroni and S. endius were
      strongly attracted to odor associated with equine manure against clean air.
      Although S. cameroni was attracted to all bovine manure-containing treatments
      against clean air, S. endius was only attracted to the bovine manure with third
      instar flies. There were no significant differences between the Spalangia species
      in odor responses. Neither Muscidifurax species were attracted to equine manure
      treatments and were only attracted to the bovine manure with puparia over clean
      air. In manure comparison studies, bovine treatments with developing flies were
      more attractive than the equivalent equine treatments to both Muscidifurax
      species The data suggest that coexistence between the competing pteromalid
      parasitoids might be promoted by different host-seeking behaviors. Additionally,
      manure preferences may indicate parasitoid suitability for releases on different
      livestock and equine facilities. 

PMID- 26314023
TI  - Impact of an Alien Invasive Shrub on Ecology of Native and Alien Invasive
      Mosquito Species (Diptera: Culicidae).
AB  - We examined how leaf litter of alien invasive honeysuckle (Lonicera maackii
      Rupr.) either alone or in combination with leaf litter of one of two native tree
      species, sugar maple (Acer saccharum Marshall) and northern red oak (Quercus
      rubra L.), affects the ecology of Culex restuans Theobald, Ochlerotatus
      triseriatus Say, and Ochlerotatus japonicus Theobald. Experimental mesocosms
      containing single species litter or a mixture of honeysuckle and one of two
      native tree species litter were established at South Farms and Trelease Woods
      study sites in Urbana, IL, and examined for their effect on 1) oviposition site
      selection by the three mosquito species, and 2) adult production and body size of
      Oc. triseriatus and Oc. japonicus. There were no significant effects of study
      site and leaf treatment on Oc. japonicus and Oc. triseriatus oviposition
      preference and adult production. In contrast, significantly more Cx. restuans
      eggs rafts were collected at South Farms relative to Trelease Woods and in
      honeysuckle litter relative to native tree species litter. Significantly larger
      adult females of Oc. japonicus and Oc. triseriatus were collected at South Farms
      relative to Trelease Woods and in honeysuckle litter relative to native tree
      species litter. Combining honeysuckle litter with native tree species litter had
      additive effects on Cx. restuans oviposition preference and Oc. japonicus and Oc.
      triseriatus body size, with the exception of honeysuckle and northern red oak
      litter combination, which had antagonistic effects on Oc. triseriatus body size.
      We conclude that input of honeysuckle litter into container aquatic habitats may
      alter the life history traits of vector mosquito species. 

PMID- 26314024
TI  - Growth of Larval Agrilus planipennis (Coleoptera: Buprestidae) and Fitness of
      Tetrastichus planipennisi (Hymenoptera: Eulophidae) in Blue Ash (Fraxinus
      quadrangulata) and Green Ash (F. pennsylvanica).
AB  - Emerald ash borer (Agrilus planipennis Fairmaire) is an invasive primary pest of
      North American ash (Fraxinus spp.) trees. Blue ash (F. quadrangulata) is less
      susceptible to emerald ash borer infestations in the forest than other species of
      North American ash. Whereas other studies have examined adult host preferences,
      we compared the capacity of emerald ash borer larvae reared from emerald ash
      borer eggs in the field and in the laboratory to survive and grow in blue ash and
      the more susceptible green ash (F. pennsylvanica). Emerald ash borer larval
      survivorship was the same on both ash species. Mortality due to wound periderm
      formation was only observed in living field grown trees, but was low (<4%) in
      both green and blue ash. No difference in larval mortality in the absence of
      natural enemies suggests that both green and blue ash can support the development
      of emerald ash borer. Larvae reared from eggs on blue ash were smaller than on
      green ash growing in the field and also in bolts that were infested under
      laboratory conditions. In a laboratory study, parasitism rates of confined
      Tetrastichus planipennisi were similar on emerald ash borer larvae reared in blue
      and green ash bolts, as were fitness measures of the parasitoid including brood
      size, sex ratio, and adult female size. Thus, we postulate that emerald ash borer
      larvae infesting blue ash could support populations of T. planipennisi and serve
      as a potential reservoir for this introduced natural enemy after most of the
      other native ash trees have been killed. 

PMID- 26314025
TI  - Repeated Cold Exposure Effects on Mortality and Feeding Activity of the Salvinia
      Weevil, Cyrtobagous salviniae (Coleoptera: Curculionidae).
AB  - Biological control of the aquatic fern, Salvinia molesta D. S. Mitchell, by
      Cyrtobagous salviniae Calder and Sands (Coleoptera: Curculionidae), in temperate
      regions has been less reliable relative to tropical and subtropical regions. High
      mortality of overwintering adults is presumed to be an important factor. At
      temperate sites, overwintering adult C. salviniae may experience multiple
      exposures to low temperatures that could compound to lethal levels. We examined
      the effects of repeated cold exposure (RCE) on the overwintering mortality and
      feeding rate of adult C. salviniae. Mortality rate of adults following exposure
      to 2, 4, and 6 cycles of RCE was 22, 70 and 82%, respectively. Mortality in the
      RCE treatment was similar to that in the matched-cold treatment for 2 and 6
      cycles but was significantly less than in the matched-cold treatment for the 4
      cycles. The relationship between the number of RCE and adult mortality rate was
      modeled and model results were compared to adult survival of caged weevils during
      four winters on two lakes in northeast Texas. Also, the feeding activity of adult
      weevils surviving RCE declined following exposure to 4 and 6 cycles of RCE. These
      results provide insight into how cold impacts overwintering survival of C.
      salviniae and should assist in anticipating the need for inoculative releases of
      C. salviniae the following spring to achieve consistent biological control of S.
      molesta at temperate locales. 

PMID- 26314026
TI  - Development and Fecundity Performance of Oriental Fruit Moth (Lepidoptera:
      Tortricidae) Reared on Shoots and Fruits of Peach and Pear in Different Seasons.
AB  - The oriental fruit moth Grapholita molesta (Busck) is a globally important insect
      pest. In some parts of its geographic range, the oriental fruit moth shifts its
      attack from peach orchards to pear orchards late in the growing season. The
      phenological effects of host plants on the performance of the moth were evaluated
      by examining the development and fecundity of the moth reared on peach (Prunus
      persica variety "Shahong") and pear (Pyrus bretshneideri variety "Dangshan Su")
      collected at various times of the growing season under laboratory conditions.
      Results showed that the moth developed faster on shoots and fruits of peach than
      on those of pear. The preimaginal survival rate was the highest on peach shoots,
      and the moth could not survive on pear fruit collected on May 10. For both peach
      and pear, the boring rates of neonatal larvae were significantly higher on shoots
      than on fruits, and the pupal mass of females was significantly higher on fruits
      than on shoots. The boring rate increased with pear fruits growing during later
      days. Fecundity was significantly less on pear shoots than on the other plant
      materials. The results of this study suggest a possible host adaptation process
      in oriental fruit moth. 

PMID- 26314027
TI  - Do Phoretic Mites Influence the Reproductive Success of Ips grandicollis
      (Coleoptera: Curculionidae)?
AB  - Ips grandicollis (Eichhoff) can be an important pest of plantation trees in the
      Great Lakes region. Mites commonly occur in phoretic association with this
      beetle, but little is known about their effects on beetle population dynamics. We
      assessed the effects of phoretic mites on the reproductive success of I.
      grandicollis using complementary correlative and manipulative approaches. First,
      we allowed beetles to colonize Pinus resinosa (Ait) logs from sites across
      Wisconsin, reared them in a common environment, and related the species
      identities and abundances of mites with beetle production from each log. We found
      a positive relationship between I. grandicollis abundance and the presence of
      five mite species, Histiostoma spp., Dendrolaelaps quadrisetus (Berlese),
      Iponemus confusus (Lindquist), Trichouropoda australis Hirschmann, and Tarsonemus
      spp. While the abundance of individual mite species was positively correlated
      with beetle abundance, assessments of mite community structure did not explain
      beetle reproduction. Next, we introduced beetles that either had a natural
      complement of mites or whose mites were mechanically reduced into logs, and
      compared reproductive success between these beetles. We found no difference in
      colonization rates or beetle emergence between mite-present and mite-reduced
      treatments. Collectively, these results suggest a correlative, rather than
      causal, link between beetle reproductive success and mite incidence and
      abundances. These mites and beetles likely benefit from mutually suitable
      environments rather than exerting strong reciprocal impacts. Although mites may
      have some effects on I. grandicollis reproductive success, they likely play a
      minimal role compared to factors such as tree quality, beetle predation, and
      weather. 

PMID- 26314028
TI  - Colonization of Artificially Stressed Black Walnut Trees by Ambrosia Beetle, Bark
      Beetle, and Other Weevil Species (Coleoptera: Curculionidae) in Indiana and
      Missouri.
AB  - Thousand cankers disease (TCD) is a new disease of black walnut (Juglans nigra
      L.) in the eastern United States. The disease is caused by the interaction of the
      aggressive bark beetle Pityophthorus juglandis Blackman and the canker-forming
      fungus, Geosmithia morbida M. Kolarik, E. Freeland, C. Utley & Tisserat, carried
      by the beetle. Other insects also colonize TCD-symptomatic trees and may also
      carry pathogens. A trap tree survey was conducted in Indiana and Missouri to
      characterize the assemblage of ambrosia beetles, bark beetles, and other weevils
      attracted to the main stems and crowns of stressed black walnut. More than 100
      trees were girdled and treated with glyphosate (Riverdale Razor Pro, Burr Ridge,
      Illinois) at 27 locations. Nearly 17,000 insects were collected from logs
      harvested from girdled walnut trees. These insects represented 15 ambrosia
      beetle, four bark beetle, and seven other weevil species. The most abundant
      species included Xyleborinus saxeseni Ratzburg, Xylosandrus crassiusculus
      Motschulsky, Xylosandrus germanus Blandford, Xyleborus affinis Eichhoff, and
      Stenomimus pallidus Boheman. These species differed in their association with the
      stems or crowns of stressed trees. Multiple species of insects were collected
      from individual trees and likely colonized tissues near each other. At least
      three of the abundant species found (S. pallidus, X. crassiusculus, and X.
      germanus) are known to carry propagules of canker-causing fungi of black walnut.
      In summary, a large number of ambrosia beetles, bark beetles, and other weevils
      are attracted to stressed walnut trees in Indiana and Missouri. Several of these
      species have the potential to introduce walnut canker pathogens during
      colonization. 

PMID- 26314029
TI  - Sublethal Effect of Imidacloprid on Solenopsis invicta (Hymenoptera: Formicidae)
      Feeding, Digging, and Foraging Behavior.
AB  - There is increasing evidence that exposure to neonicotinoid insecticides at
      sublethal levels impairs colonies of honeybees and other pollinators. Recently,
      it was found that sublethal contamination with neonicotinoids also affect growth
      and behavior of ants. In this study, we exposed red imported fire ants,
      Solenopsis invicta Buren, to sublethal dosages of dietary imidacloprid and
      investigated its effect on ant feeding, digging, and foraging behavior. S.
      invicta consumed significantly more sugar water containing 0.01 MUg/ml
      imidacloprid than untreated sugar water. Ants fed with 0.01 MUg/ml imidacloprid
      also showed significantly increased digging activity than ants fed with untreated
      sugar water. However, imidacloprid at >= 0.25 MUg/ml significantly suppressed
      sugar water consumption, digging, and foraging behavior. These results indicate
      that imidacloprid at sublethal concentrations may have a significant and
      complicated effect on S. invicta.

PMID- 26314030
TI  - A Multiple Decrement Life Table Reveals That Host Plant Resistance and Parasitism
      Are Major Causes of Mortality for the Wheat Stem Sawfly.
AB  - This study investigated the dynamics of parasitism, host plant resistance,
      pathogens, and predation on the demography of wheat stem sawfly, Cephus cinctus
      Norton (Hymenoptera: Cephidae), developing in susceptible (hollow stem) and
      resistant (solid stem) wheat hosts. This study is also the first to investigate
      the prevalence and impact of cannibalism on wheat stem sawfly mortality. Wheat
      stem sawflies were sampled in two commercial wheat fields over 4 yr from the egg
      stage through adult emergence, and multiple decrement life tables were
      constructed and analyzed. Cannibalism, host plant resistance, or unknown factors
      were the most prevalent factors causing egg mortality. Summer mortality of
      prediapause larvae ranged from 28 to 84%, mainly due to parasitism by Bracon
      cephi (Gahan) and Bracon lissogaster Muesebeck, cannibalism, and host plant
      resistance. Winter mortality ranged from 6 to 54% of the overwintering larvae,
      mainly due to unknown factors or pathogens. Cannibalism is a major cause of
      irreplaceable mortality because it is absolute, with only a single survivor in
      every multiple infested stem. Subsequent to obligate cannibalism, mortality of
      feeding larvae due to host plant resistance was lower in hollow stem wheat than
      in solid stem wheat. Mortality from host plant resistance was largely
      irreplaceable. Irreplaceable mortality due to parasitoids was greater in hollow
      stem wheat than in solid stem wheat. Host plant resistance due to stem solidness
      and parasitism in hollow stems cause substantial mortality in populations of
      actively feeding larvae responsible for all crop losses. Therefore, enhancing
      these mortality factors is vital to effective integrated pest management of wheat
      stem sawfly. 

PMID- 26314031
TI  - Population Growth of the Generalist Mite Tyrophagus putrescentiae (Acari:
      Acaridida) Following Adaptation to High- or Low-Fat and High- or Low-Protein
      Diets and the Effect of Dietary Switch.
AB  - Tyrophagus putrescentiae (Schrank, 1781) is a cosmopolitan generalist feeder that
      prefers foodstuffs of high-fat and high-protein content. Our aim was to
      investigate the population growth of T. putrescentiae after long-term nutritional
      adaptation to two distinct diets that are commonly infested in the synanthropic
      environment. Crushed dry dog food kernels provided a high-fat, high-protein, and
      low-carbohydrate diet, whereas wholemeal spelt flour provided a low-protein, low
      fat, and high-carbohydrate diet. After >6 mo of nutritional adaptation, each of
      the two populations were used in two 28-d population growth tests: one that mites
      remained on their adaptation diet (homogenous diet treatment) and one that mites
      underwent a dietary switch (dietary switch treatment). Dietary treatment,
      nutritional adaptation, and their interaction all significantly influenced
      population growth. The homogenous diet treatment showed 7.5 times higher growth
      on the dog food diet than on flour. In the dietary switch, flour-adapted mites
      switching to dog food experienced five times greater population growth than the
      flour-adapted mites remained on flour, whereas the dog food-adapted population
      showed a 2.8-fold decrease in population growth when transferred to the flour. A
      comparison of means between the two dietary switch treatments showed a 1.9-fold
      higher population growth after flour-adapted mites were shifted to dog food than
      when the dog food-adapted mites were shifted to flour. We demonstrated that T.
      putrescentiae is able survive and reproduce for many generations on dry dog food
      and flour with different levels of success. High-fat and -protein food
      accelerated T. putrescentiae population growth compared with the high
      carbohydrate diet.

PMID- 26314032
TI  - Changes in Orchid Bee Communities Across Forest-Agroecosystem Boundaries in
      Brazilian Atlantic Forest Landscapes.
AB  - Deforestation has dramatically reduced the extent of Atlantic Forest cover in
      Brazil. Orchid bees are key pollinators in neotropical forest, and many species
      are sensitive to anthropogenic interference. In this sense understanding the
      matrix permeability for these bees is important for maintaining genetic diversity
      and pollination services. Our main objective was to assess whether the
      composition, abundance, and diversity of orchid bees in matrices differed from
      those in Atlantic forest. To do this we sampled orchid bees at 4-mo intervals
      from 2007 to 2009 in remnants of Atlantic Forest, and in the surrounding pasture
      and eucalyptus matrices. The abundance, richness, and diversity of orchid bees
      diminished significantly from the forest fragment toward the matrix points in the
      eucalyptus and pasture. Some common or intermediate species in the forest areas,
      such as Eulaema cingulata (F.) and Euglossa fimbriata Moure, respectively, become
      rare species in the matrices. Our results show that the orchid bee community is
      affected by the matrices surrounding the forest fragments. They also suggest that
      connections between forest fragments need to be improved using friendly matrices
      that can provide more favorable conditions for bees and increase their dispersal
      between fragments. 

PMID- 26314033
TI  - Joint Effect of Solar UVB and Heat Stress on the Seasonal Change of Egg Hatching
      Success in the Herbivorous False Spider Mite (Acari: Tenuipalpidae).
AB  - Seasonal population dynamics of an herbivorous mite has been documented in terms
      of the relationship between thermoresponses and temporal biological factors such
      as resource availability or predation risk. Although recent studies emphasize the
      deleterious effects of solar ultraviolet-B (UVB; 280-320 nm wavelengths)
      radiation on plant-dwelling mites, how UVB affects mite population remains
      largely unknown. On a wild shrub Viburnum erosum var. punctatum in Kyoto, an
      herbivorous false spider mite, Brevipalpus obovatus Donnadieu, occurs only in
      autumn. Females of this species lay one-third of their eggs on upper leaf
      surfaces. Oviposition on upper surfaces is beneficial for avoiding predation by
      phytoseiids, but exposes eggs to solar UVB and heat stress. To test the
      hypothesis that the seasonal occurrence of this mite is determined by
      interactions between solar UVB radiation and temperature, we examined variation
      in egg hatching success under near-ambient and UV-attenuated sunlight conditions
      from spring to autumn. The UV-attenuation significantly improved hatching
      success. However, most eggs died under heat stress regardless of UV treatments in
      July and August. We established a deterministic heat stress-cumulative UVB dose
      egg hatching success response model, which we applied to meteorological data. The
      model analyses illustrated lower and higher survivability peaks in late May and
      October, respectively, which partly corresponded to data for annual field
      occurrence, indicating the importance of solar UVB radiation and heat stress as
      determinants of the seasonal occurrence of this mite. 

PMID- 26314034
TI  - Diel Patterns of Colaspis brunnea and Colaspis crinicornis (Coleoptera:
      Chrysomelidae) in Southeastern Nebraska.
AB  - A field study was conducted to increase our understanding of diel activity
      patterns of Colaspis brunnea (F.) and Colaspis crinicornis Schaeffer (Coleoptera:
      Chrysomelidae) in key crop habitats. Within 24-h periods, C. brunnea was sampled
      in clover fields (primarily red clover, Trifolium pretense (L.), with some sweet
      clover, Melilotus officinalis (L.) Pallas, and downy brome, Bromus tectorum (L.))
      and soybean, Glycine max (L.) Merrill, fields, using a sweep-net, while whole
      plant-count sampling was used to monitor C. crinicornis densities in field corn,
      Zea mays (L.). Sweep-net captures of C. brunnea were significantly greater at
      night than during the day, suggesting possible vertical movement within the
      canopy during a 24-h period. Colaspis crinicornis densities on corn plants were
      fairly constant throughout a 24-h period, but beetle activity (e.g., walking,
      mating) was significantly greater at night than during the day. Results suggest
      that both Colaspis species may be exhibiting similar increases in activity at
      night that facilitates movement from more protected to more exposed areas within
      a habitat. It is unclear what mechanisms drive this diel pattern, but vegetation
      architecture and associated interactions with environmental conditions may play a
      role. Sweep-netting in clover or soybean fields and use of whole-plant-counts in
      cornfields were effective sampling methods for Colaspis adults. However, because
      activity and behaviors of Colaspis beetles were influenced by time of day in this
      study, use of a consistent sampling time within a diel period would be
      recommended for future population studies or integrated pest management decision
      making. 

PMID- 26314035
TI  - The Effect of Ultraviolet-A Radiation Exposure on the Reproductive Ability,
      Longevity, and Development of the Dialeurodes citri (Homoptera: Aleyrodidae) F1
      Generation.
AB  - Ultraviolet (UV) light has been used worldwide to monitor and trap insect pests.
      Whitefly adults show conspicuous positive phototactic behavior toward UV light
      stimuli; however, knowledge of the effect of UV light exposure on various life
      history parameters of Dialeurodes citri remains limited. The present research
      aimed to investigate the effect of ultraviolet radiation (UV-A; long-wave)
      exposure on the reproduction and longevity of D. citri adults as well as the
      development of immature (eggs, larvae, and pupae) flies in the F1 generation.
      Paired D. citri adults were exposed to UV-A radiation for different periods (0,
      1, 4, and 7 h/d) until the end of their life. The results of the experiment
      revealed that fecundity and oviposition rates increased when adults were
      irradiated for 1 and 4 h/d, but interestingly, both were significantly decreased
      compared with those of the controls after the longest exposure time (7 h/d). The
      longevity of adults of both sexes and the cumulative survival of F1 immatures
      were decreased with increased exposure time. Exposure to UV-A radiation prolonged
      the developmental time of immature stages, and a positive correlation was
      observed with exposure time. Exposure to UV light significantly inhibited egg
      hatching, larval development, pupation, and adult emergence. To the best of our
      knowledge, this is the first study describing the effect of UV radiation on a
      homopteran insect pest. This research may provide a foundation for the scientific
      community to use UV light in the field as an integrated pest management strategy
      to control this devastating agricultural pest.

PMID- 26314036
TI  - Behavioral Responses of Laricobius spp. and Hybrids (Coleoptera: Derodontidae) to
      Hemlock Woolly Adelgid and Adelgid Host Tree Odors in an Olfactometer.
AB  - The predatory species Laricobius nigrinus (Fender) and Laricobius osakensis
      (Shiyake and Montgomery) (Coleoptera: Derodontidae) have been released for
      biological control of hemlock woolly adelgid (Adelges tsugae; Hemiptera:
      Adelgidae) in eastern North America. L. osakensis is native to Japan, whereas L.
      nigrinus is endemic to the Pacific Northwest of the United States and Canada.
      After release, L. nigrinus was found to hybridize with the native eastern
      species, Laricobius rubidus (LeConte). The purpose of this study is to observe
      prey location behaviors of these three Laricobius species and L. nigrinus * L.
      rubidus (Ln * Lr) hybrids. Olfactometer bioassays were used to test response to
      host odors of adelgid-infested eastern hemlock, uninfested eastern hemlock, and
      uninfested eastern white pine. Predators reacted in the olfactometer more quickly
      when adelgid-infested foliage was included as a choice. L. nigrinus preferred
      infested eastern hemlock over uninfested eastern white pine, and L. rubidus
      preferred uninfested eastern white pine over uninfested eastern hemlock.
      Laricobius hybrids did not show a preference for foliage types known to be
      primary adelgid hosts (eastern hemlock and eastern white pine). Unequal
      preference by species of Laricobius for host trees of different adelgid prey
      could therefore be maintaining Laricobius species barriers despite hybridization.
      L. osakensis for this study were reared in the laboratory, whereas other species
      in this study were collected from the field, yet still were attracted to infested
      and uninfested eastern hemlock. This species also responded most quickly in the
      olfactometer, which is encouraging for successful biological control with this
      species. 

PMID- 26314037
TI  - Long-Distance Dispersal Potential for Onion Thrips (Thysanoptera: Thripidae) and
      Iris yellow spot virus (Bunyaviridae: Tospovirus) in an Onion Ecosystem.
AB  - Onion thrips, Thrips tabaci Lindeman, is a worldwide pest of onion whose feeding
      damage and transmission of Iris yellow spot virus (IYSV) may reduce onion yields.
      Little is known about the seasonal dynamics of T. tabaci dispersal, the distance
      of dispersal, or the movement of thrips infected with IYSV during the onion
      growing season. To address these questions, T. tabaci adults were collected using
      transparent sticky card traps in commercial onion fields three times during the
      onion-growing season (June, July, and late August) at varying heights above the
      canopy (0.5-6 m above soil surface) and with trap-equipped unmanned aircraft
      (UAVs) flying 50-60 m above onion fields during August sampling periods in 2012
      and 2013. Randomly selected subsamples of captured T. tabaci were tested for IYSV
      using RT-PCR. Most T. tabaci adults were captured in late August and near the
      onion canopy (<2 m) throughout the season. However, 4% of T. tabaci adults
      captured on sticky cards were at altitudes >=2 m, and T. tabaci were also
      captured on UAV-mounted traps. These data strongly suggest that long-distance
      dispersal occurs. More T. tabaci captured on sticky cards tested positive for
      IYSV in August (53.6%) than earlier in the season (2.3 to 21.5% in June and July,
      respectively), and 20 and 15% of T. tabaci captured on UAV-mounted traps tested
      positive for IYSV in 2012 and 2013, respectively. Our results indicate that T.
      tabaci adults, including viruliferous individuals, engage in long-distance
      dispersal late in the season and likely contribute to the spread of IYSV.

PMID- 26314038
TI  - Seasonal Abundance and Phenology of Oebalus pugnax (Hemiptera: Pentatomidae) on
      Graminaceous Hosts in the Delta Region of Mississippi.
AB  - The rice stink bug, Oebalus pugnax (F.), is a graminaceous feeder, and the most
      injurious insect pest of heading rice, Oryza sativa L., in the United States.
      Rice growers are aware of the economic importance of host grasses in O. pugnax
      abundance. However, the need for increased knowledge of host sequence relative to
      O. pugnax abundance is vital. Densities of O. pugnax on 15 graminaceous hosts
      were evaluated in the central Mississippi Delta from April through August in 2011
      and 2012. Two cultivated and 13 wild host grasses were sampled using a sweep net.
      Overall, populations of O. pugnax were lower in 2012 than in 2011. Italian
      ryegrass, Lolium perenne L. ssp. multiflorum (Lambert), was the main host that
      supported O. pugnax survival and reproduction from overwintering to early summer.
      Echinochloa spp., Digitaria spp., and Eriochloa spp. maintained greater
      populations of O. pugnax in the summer. Browntop millet, Urochloa ramosa (L.)
      Nguyen, and broadleaf signalgrass, U. platyphylla (Munro ex C. Wright) R. D.
      Webster, were important for populations of O. pugnax populations immediately
      prior to overwintering. Host switching was also an important factor that
      contributed to O. pugnax abundance. The evolution of Italian ryegrass resistance
      to the broad spectrum herbicide glyphosate in the central Mississippi delta has
      become an important component of O. pugnax population dynamics because of its
      increased abundance in and around agricultural areas. Cultural control measures
      on host grasses before flowering could result in less use of insecticides,
      thereby reducing cost of rice production.

PMID- 26314039
TI  - Local and Landscape Drivers of Ant Parasitism in a Coffee Landscape.
AB  - Parasitism of ants that nest in rotting wood by eucharitid wasps was studied in
      order to examine whether habitat and season influence ant parasitism, vegetation
      complexity and agrochemical use correlate with ant parasitism, and whether
      specific local and landscape features of agricultural landscapes correlate with
      changes in ant parasitism. In a coffee landscape, 30 coffee and 10 forest sites
      were selected in which local management (e.g., vegetation, agrochemical use) and
      landscape features (e.g., distance to forest, percent of rustic coffee nearby)
      were characterized. Rotten logs were sampled and ant cocoons were collected from
      logs and cocoons were monitored for parasitoid emergence. Sixteen ant
      morphospecies in three ant subfamilies (Ectatomminae, Ponerinae, and Formicinae)
      were found. Seven ant species parasitized by two genera of Eucharitidae
      parasitoids (Kapala and Obeza) were reported and some ant-eucharitid associations
      were new. According to evaluated metrics, parasitism did not differ with habitat
      (forest, high-shade coffee, low-shade coffee), but did increase in the dry season
      for Gnamptogenys ants. Parasitism increased with vegetation complexity for
      Gnamptogenys and Pachycondyla and was high in sites with both high and low
      agrochemical use. Two landscape variables and two local factors positively
      correlated with parasitism for some ant genera and species. Thus, differences in
      vegetation complexity at the local and landscape scale and agrochemical use in
      coffee landscapes alter ecological interactions between parasitoids and their ant
      hosts.

PMID- 26314040
TI  - Impact of Location, Cropping History, Tillage, and Chlorpyrifos on Soil
      Arthropods in Peanut.
AB  - Demand for agricultural production systems that are both economically viable and
      environmentally conscious continues to increase. In recent years, reduced tillage
      systems, and grass and pasture rotations have been investigated to help maintain
      or improve soil quality, increase crop yield, and decrease labor requirements for
      production. However, documentation of the effects of reduced tillage, fescue
      rotation systems as well as other management practices, including pesticides, on
      pest damage and soil arthropod activity in peanut production for the Mid-Atlantic
      US region is still limited. Therefore, this project was implemented to assess
      impacts of fescue-based rotation systems on pests and other soil organisms when
      compared with cash crop rotation systems over four locations in eastern North
      Carolina. In addition, the effects of tillage (strip vs. conventional) and soil
      chlorpyrifos application on pod damage and soil-dwelling organisms were also
      evaluated. Soil arthropod populations were assessed by deploying pitfall traps
      containing 50% ethanol in each of the sampled plots. Results from the present
      study provide evidence that location significantly impacts pest damage and soil
      arthropod diversity in peanut fields. Cropping history also influenced arthropod
      diversity, with higher diversity in fescue compared with cash crop fields. Corn
      rootworm damage to pods was higher at one of our locations (Rocky Mount) compared
      with all others. Cropping history (fescue vs. cash crop) did not have an effect
      on rootworm damage, but increased numbers of hymenopterans, acarina,
      heteropterans, and collembolans in fescue compared with cash crop fields.
      Interestingly, there was an overall tendency for higher number of soil arthropods
      in traps placed in chlorpyrifos-treated plots compared with nontreated controls.

PMID- 26314041
TI  - Potential for Interspecific Competition Between Congeneric Longhorned Beetle
      Species (Coleoptera: Cerambycidae) in an Adventive Environment.
AB  - The cerambycid beetle, Phoracantha semipunctata F., was introduced into
      California in the mid-1980s and killed large numbers of Eucalyptus host trees.
      The populations of the borer declined to very low levels in the mid-1990s
      following the establishment of the congener, Phoracantha recurva Newman, and the
      intentional introduction of the egg parasitoid, Avetianella longoi Siscaro. The
      distributions of the beetles overlap in the Australian native range, but one
      species has replaced the other in the adventive range in California. One possible
      explanation is differential susceptibility to natural enemies introduced for
      biological control. An alternative explanation for the reduced abundance of P.
      semipunctata is asymmetric interspecific competition between the two species. To
      test this hypothesis, equal larval densities of each species were introduced into
      host logs. In all cases, more P. recurva adults emerged than P. semipunctata
      adults, but the presence of congeners did not have a different effect than the
      presence of an equal density of conspecific individuals. Neither the temporal
      order of introduction or bark thickness altered the outcome of potential
      competitive interactions. Consequently, it appears that the ecological
      replacement of one borer with another in the adventive environment in southern
      California may not be a result of bottom-up intraguild competitive interactions.
      The top-down effects of natural enemies on P. semipunctata have most likely led
      to its decline.

PMID- 26314042
TI  - Necrophilous Histerid Beetle Communities (Coleoptera: Histeridae) in Central
      Spain: Species Composition and Habitat Preferences.
AB  - Despite the applied importance of necrophilous histerid beetles, their
      communities and habitat preferences had not been characterized in the Iberian
      Peninsula. The current article describes the composition of those communities in
      seven types of natural habitats along a bioclimatical gradient in central Spain,
      describing and discussing the habitat preferences and niche breadths of the most
      abundant species. In total, 25 species of necrophilous Histeridae were collected
      using carrion-baited traps. As a result, six groups of species can be
      distinguished according to their habitat preferences. These groupings depend on
      either the distribution among habitats or their restriction to certain habitats.
      Moreover, within each habitat, the type of vegetation was a factor structuring
      histerid communities, with those species with wide distribution throughout
      several habitats showing a preference for more open areas. 

PMID- 26314043
TI  - Abundance and Diversity of Wild Bees (Hymenoptera: Apoidea) Found in Lowbush
      Blueberry Growing Regions of Downeast Maine.
AB  - Insect-mediated pollination is critical for lowbush blueberry (Ericaceae:
      Vaccinium angustifolium Aiton) fruit development. Past research shows a
      persistent presence of wild bees (Hymenoptera: Apoidea) providing pollination
      services even when commercial pollinators are present. We undertook the study to
      1) provide a description of bee communities found in lowbush blueberry-growing
      regions, 2) identify field characteristics or farm management practices that
      influence those communities, 3) identify key wild bee pollinators that provide
      pollination services for the blueberry crop, and 4) identify non-crop plants
      found within the cropping system that provide forage for wild bees. During a 4
      year period, we collected solitary and eusocial bees in over 40 fields during and
      after blueberry bloom, determining a management description for each field. We
      collected 4,474 solitary bees representing 124 species and 1,315 summer bumble
      bees representing nine species. No bumble bee species were previously unknown in
      Maine, yet we document seven solitary bee species new for the state. These
      include species of the genera Nomada, Lasioglossum, Calliopsis, and
      Augochloropsis. No field characteristic or farm management practice related to
      bee community structure, except bumble bee species richness was higher in
      certified organic fields. Pollen analysis determined scopal loads of 67-99%
      ericaceous pollen carried by five species of Andrena. Our data suggest two native
      ericaceous plants, Kalmia angustifolia L. and Gaylussacia baccata (Wangenheim),
      provide important alternative floral resources. We conclude that Maine blueberry
      croplands are populated with a species-rich bee community that fluctuates in time
      and space. We suggest growers develop and maintain wild bee forage and nest
      sites.

PMID- 26314044
TI  - An Investigation into the Physico-chemical Factors Affecting the Abundance and
      Diversity of Aquatic Insects in Organically Manured Aquadams and Their
      Utilization by Oreochromis mossambicus (Perciformes: Cichlidae).
AB  - The interaction between the fish Oreochromis mossambicus (Percifomes: Cichlidae)
      and aquatic insects after application of chicken, cow, and pig manure was studied
      in 7,000-liter plastic aquadams. Principal component analysis showed that most of
      the variation in water quality after application of manure was accounted for by
      potassium, nitrogen, dissolved oxygen, phosphate, and alkalinity. Canonical
      correspondence analysis showed that Gyrinidae, Elminidae, Hydrophilidae,
      Hydraenidae, and Athericidae were associated with high nutrient levels (nitrogen,
      phosphorus, and potassium) characteristic of the chicken manure. However, the
      most abundant aquatic insects Gerridae, Notonectidae, and Culicidae were close to
      the centre of the ordination and not defined by any nutrient gradient. The
      Shannon-Wiener diversity was highest in the aquadams treated with chicken manure.
      The most frequently occurring aquatic insects in the diet of O. mossambicus were
      culicid mosquitoes in all the treatments. However, in the laboratory,
      Chironomidae were the most preferred because they lacked refuge. Notonectidae and
      Gerridae were not recorded in the diet of O. mossambicus despite their abundance.
      This may be because of their anti-predation strategies. Laboratory experiments
      showed that Notonectidae, Gyrinidae, and Gerridae fed on Chironomidae and
      Culicidae. This implies that aquatic predatory insects competed for food with O.
      mossambicus.

PMID- 26314045
TI  - Management of Overwintering Cover Crops Influences Floral Resources and
      Visitation by Native Bees.
AB  - The incorporation of cover crops into annual crop rotations is one practice that
      is used in the Mid-Atlantic United States to manage soil fertility, suppress
      weeds, and control erosion. Additionally, flowering cover crops have the
      potential to support beneficial insect communities, such as native bees. Because
      of the current declines in managed honey bee colonies, the conservation of native
      bee communities is critical to maintaining "free" pollination services. However,
      native bees are negatively affected by agricultural intensification and are also
      in decline across North America. We conducted two experiments to assess the
      potential of flowering cover crops to act as a conservation resource for native
      bees. We evaluated the effects of cover crop diversity and fall planting date on
      floral resource availability and visitation by native bees for overwintering
      flowering cover crop species commonly used in the Mid-Atlantic region. Cover crop
      species, crop rotation schedule, and plant diversity significantly influenced
      floral resource availability. Different cover crop species not only had different
      blooming phenologies and winter survival responses to planting date, but
      attracted unique bee communities. Flower density was the primary factor
      influencing frequency of bee visitation across cover crop diversity and fall
      planting date treatments. The results from these experiments will be useful for
      informing recommendations on the applied use of flowering cover crops for
      pollinator conservation purposes.

PMID- 26314046
TI  - Occurrence of Brown Marmorated Stink Bug (Hemiptera: Pentatomidae) on Wild Hosts
      in Nonmanaged Woodlands and Soybean Fields in North Carolina and Virginia.
AB  - Nonmanaged plants occurring along forest edges and in suburban settings were
      sampled for brown marmorated stink bug, Halyomorpha halys (Stal), in North
      Carolina (NC) and Virginia (VA) over the course of three growing seasons.
      Commercial soybeans (Glycine max), an attractive cultivated host, were also
      sampled in 2014 in NC and in VA from 2010-2014. Very few H. halys were found on
      nonmanaged plants or soybean fields in the coastal plain region of either state,
      but substantial populations were recorded in the piedmont and mountain regions.
      From 2011 to 2013, H. halys comprised from 51 to 97% of all stink bug species
      observed on nonmanaged plants in the piedmont and mountain regions. In VA, the
      distribution expanded from detection in 12 counties in 2010 to 53 counties in
      2014, with economically damaging levels occurring in the piedmont region. During
      these studies, H. halys were observed to complete one and a partial second
      generation per year in western NC and southwestern VA, similar to that previously
      observed in regions farther north. Several plants were identified as preferred
      hosts, with tree of heaven, catalpa, yellowwood, paulownia, cherry, walnut,
      redbud, and grape having consistently high numbers of H. halys. Knowing that
      these plants are preferred by H. halys during certain stages of the insects'
      development will aid in the search for H. halys in new areas, as well as serve as
      one predictor of the likelihood of a certain area to attract and sustain large H.
      halys populations.

PMID- 26314047
TI  - Population Dynamics of Culex restuans and Culex pipiens (Diptera: Culicidae)
      Related to Climatic Factors in Northwest Ohio.
AB  - Two species of Culex mosquitoes are common throughout much of North America.
      Culex restuans Theobold is a native species, whereas Culex pipiens L. is a
      European immigrant that has been in North America since the 1600s. Larvae of Cx.
      restuans are numerically dominant in spring and early summer but Cx. pipiens
      dominates by mid-summer. This transition is termed the "Culex crossover" and has
      been previously explored in larval populations, largely because Cx. pipiens is
      more likely to transfer West Nile virus to humans. Adult mosquitoes of both
      species were captured in 14 light traps in Lucas County, OH, between May and
      October 1980-2011. We examined this 31-yr, continuous record of adult populations
      for signs of a species crossover, relationships between abundances of both
      species and climate factors, and evidence of interspecific competition. The total
      cumulative degree-days (above 0 degrees C), total cumulative precipitation, and
      total number of each species were calculated for each day of January-September
      (annual) and May-September (mosquito season) of each year. On average, adult Cx.
      pipiens became numerically dominant over Cx. restuans on day 175 +/- 21 (June
      24), consistent with the Culex crossover reported for their larvae. Pearson
      correlations showed that abundances of both species were related to temperature
      and precipitation, but Cx. pipiens tended to be positively related to climatic
      factors, whereas Cx. restuans showed negative correlations. Moreover, abundances
      of the two species were more positively than negatively related to one another,
      providing no evidence of interspecific competition.

PMID- 26314048
TI  - Chilling and Host Plant/Site-Associated Eclosion Times of Western Cherry Fruit
      Fly (Diptera: Tephritidae) and a Host-Specific Parasitoid.
AB  - The western cherry fruit fly, Rhagoletis indifferens Curran (Diptera:
      Tephritidae), is an endemic herbivore of bitter cherry, Prunus emarginata
      (Douglas ex Hooker) Eaton, but ~100 years ago established on earlier-fruiting
      domesticated sweet cherry, Prunus avium (L.) L. Here, we determined if eclosion
      times of adult R. indifferens from sweet and bitter cherry differ according to
      the phenology of their respective host plants and if eclosion times of the host
      specific parasitoid Diachasma muliebre (Muesebeck) (Hymenoptera: Braconidae)
      attacking bitter and sweet cherry flies differ according to the eclosion
      phenology of their fly hosts. Fly pupae from sweet and bitter cherry fruit were
      collected from sympatric and allopatric sites in Washington state, and chilled at
      5 degrees C. Because timing of eclosion in R. indifferens depends on chill
      duration, eclosion time in wasps could also vary with chill duration. To account
      for this, fly pupae were chilled for 1, 2, 2.5, 3, 4, 6, or 8 mo. Both flies and
      wasps eclosed earlier with longer chill durations. Eclosion times of sweet and
      bitter cherry flies from a sympatric site in central Washington did not differ.
      However, at allopatric sites in northwestern and central Washington, bitter
      cherry flies eclosed later than sweet and bitter cherry flies at the sympatric
      site. Correspondingly, D. muliebre parasitizing a more isolated bitter cherry fly
      population eclosed later than D. muliebre parasitizing earlier-emerging sweet and
      bitter cherry fly populations. These results provide evidence for D. muliebre
      rapidly responding to changes in host plant shifts by R. indifferens.

PMID- 26314049
TI  - Local and Landscape Correlates of Spider Activity Density and Species Richness in
      Urban Gardens.
AB  - Urbanization is a major threat to arthropod biodiversity and abundance due to
      reduction and loss of suitable natural habitat. Green spaces and small-scale
      agricultural areas may provide habitat and resources for arthropods within
      densely developed cities. We studied spider activity density (a measure of both
      abundance and degree of movement) and diversity in urban gardens in Santa Cruz,
      Santa Clara, and Monterey counties in central California, USA. We sampled for
      spiders with pitfall traps and sampled 38 local site characteristics for 5 mo in
      19 garden sites to determine the relative importance of individual local factors.
      We also analyzed 16 landscape variables at 500-m and 1-km buffers surrounding
      each garden to determine the significance of landscape factors. We identified
      individuals from the most common families to species and identified individuals
      from other families to morphospecies. Species from the families Lycosidae and
      Gnaphosidae composed 81% of total adult spider individuals. Most of the
      significant factors that correlated with spider activity density and richness
      were local rather than landscape factors. Spider activity density and richness
      increased with mulch cover and flowering plant species, and decreased with bare
      soil. Thus, changes in local garden management have the potential to promote
      diversity of functionally important spiders in urban environments.

PMID- 26314050
TI  - Impacts of Contrasting Alfalfa Production Systems on the Drivers of Carabid
      Beetle (Coleoptera: Carabidae) Community Dynamics.
AB  - Growing concerns about the environmental consequences of chemically based pest
      control strategies have precipitated a call for the development of integrated,
      ecologically based pest management programs. Carabid or ground beetles
      (Coleoptera:Carabidae) are an important group of natural enemies of common
      agricultural pests such as aphids, slugs, and other beetles. Alfalfa (Medicago
      sativa L.) is one of the most common forage crop species in the semi-arid western
      United States. In 2011, Montana alone produced 4.0 * 10(6 )Mg of alfalfa on 8.1 *
      10(5 )ha for gross revenue in excess of US$4.3 * 10(8), making it the third
      largest crop by revenue. We conducted our study over the 2012 and 2013 growing
      seasons. Each year, our study consisted of three sites each with adjacent systems
      of monoculture alfalfa, alfalfa nurse cropped with hay barley, and an
      uncultivated refuge consisting of a variety of forbs and grasses. Carabid
      community structure differed and strong temporal shifts were detected during both
      2012 and 2013. Multivariate fuzzy set ordination suggests that variation in
      canopy height among the three vegetation systems was primarily responsible for
      the differences observed in carabid community structure. Land managers may be
      able to enhance carabid species richness and total abundance by creating a
      heterogeneous vegetation structure, and nurse cropping in particular may be
      effective strategy to achieve this goal.

PMID- 26314051
TI  - Indirect Effects of One Plant Pathogen on the Transmission of a Second Pathogen
      and the Behavior of its Potato Psyllid Vector.
AB  - Plant pathogens can influence the behavior and performance of insect herbivores.
      Studies of these associations typically focus on tripartite interactions between
      a plant host, a plant pathogen, and its insect vector. An unrelated herbivore or
      pathogen might influence such interactions. This study used a model system
      consisting of Tobacco mosaic virus (TMV), the psyllid Bactericera cockerelli
      Sulc, and tomatoes to investigate multipartite interactions among a pathogen, a
      nonvector, and a plant host, and determine whether shifts in host physiology were
      behind potential interactions. Additionally, the ability of TMV to affect the
      success of another pathogen, 'Candidatus Liberibacter solanacearum,' which is
      transmitted by the psyllid, was studied. In choice trials, psyllids preferred
      nearly fourfold noninfected plants to TMV-infected plants. No-choice bioassays
      demonstrated that there was no difference in psyllid development between TMV
      infected and control plants; oviposition was twice as high on control plants.
      Following inoculation by psyllids, 'Candidatus Liberibacter solanacearum' titers
      were lower in TMV-infected plants than control plants. TMV-infected plants had
      lower levels of amino acids and sugars but little differences in phenolics and
      terpenoids, relative to control plants. Possibly, these changes in sugars are
      associated with a reduction in psyllid attractiveness in TMV-infected tomatoes
      resulting in decreased infection of 'Candidatus Liberibacter solanacearum.'

PMID- 26314052
TI  - Effect of Mutual Interference on the Ability of Spalangia cameroni (Hymenoptera:
      Pteromalidae) to Attack and Parasitize Pupae of Stomoxys calcitrans (Diptera:
      Muscidae).
AB  - We investigated the effect of mutual interference on the attack efficiency and
      the rate of successful parasitism on the parasitoid Spalangia cameroni (Perkins)
      attacking pupae of the stable fly Stomoxys calcitrans (L.). Female parasitoids
      (2, 4, 8, 16, or 32) were exposed to 100 fly pupae during 24 h. The number of
      pupae that were attacked and the number successfully parasitized increased with
      the parasitoid density and reached a maximum of ~70 and 50, respectively.
      Parasitoid-induced mortality (PIM) was about 20 pupae, irrespective of parasitoid
      density. The per capita rates of attack, successful parasitism and parasitoid
      induced mortality declined monotonously with parasitoid density. Progeny sex
      ratio was female biased for all parasitoid densities, but declined significantly
      with increasing parasitoid density from ~70% females at the lowest density to
      ~60% at the highest. Mutual interference was incorporated into a functional
      response model to predict the attack rate and the rate of successful parasitism
      at different temperatures, host densities and parasitoid densities. The model
      explained 93.5% of the variation in the observed number of attacked pupae and
      91.5% of the variation in the number of successfully parasitized pupae. The model
      predicts that increasing parasitoid densities will increase the percentage of
      killed hosts, but only up to a certain density. Above this density, a further
      increase in parasitoid abundance will actually lead to a decline in the
      percentage parasitism. These findings may have some implications for using S.
      cameroni in biological control against flies using inundative releases.

PMID- 26314053
TI  - Predicting Developmental Timing for Immature Canada Thistle Stem-Mining Weevils,
      Hadroplontus litura (Coleoptera: Curculionidae).
AB  - Predictions of phenological development for insect biological control agents may
      facilitate post-release monitoring efforts by allowing land managers to optimize
      the timing of monitoring activities. A logistic thermal time model was tested to
      predict phenology of immature stem-mining weevils, Hadroplontus litura F.
      (Coleoptera: Curculionidae), a biological control agent for Canada thistle,
      Cirsium arvense L. (Asterales: Asteraceae). Weevil eggs and larvae were collected
      weekly from Canada thistle stems in eastern North Dakota from May through July
      during 2010 and 2011. Head capsule widths of sampled larvae were measured at the
      widest point and plotted on a frequency histogram to establish ranges of head
      capsule widths associated with each instar. We found head capsule width ranges
      for first-, second-, and third-instar H. litura larvae were 165-324 um, 346-490
      um, and 506-736 um, respectively. Logistic regression models were developed to
      estimate the proportions of H. litura eggs, first-, and second-instar larvae in
      the weevil population as a function of thermal time. Model estimates of median
      development time for eggs, first instars, and second instars ranged from 219 +/-
      23 degree-days (DD) to 255 +/- 27 DD, 556 +/- 77 DD to 595 +/- 81 DD, and 595 +/-
      109 DD to 653 +/- 108 DD, respectively. Based on model validation statistics,
      model estimates for development timing were the most accurate for eggs and first
      instars and somewhat less accurate for second instars. These model predictions
      will help biological control practitioners obtain more accurate estimates of
      weevil population densities during post-release monitoring.

PMID- 26314054
TI  - Gall-Insect Community on Big Sagebrush Varies With Plant Size but not Plant Age.
AB  - There is astounding variation in the abundance and diversity of insect herbivores
      among plant individuals within plant species in natural systems. One of the most
      well studied hypotheses for this pattern, the plant architecture hypothesis,
      suggests that insect community patterns vary with plant structural complexity and
      plant traits associated with structure. An important limitation to our
      understanding of the plant architecture hypothesis has been that most studies on
      the topic confound plant size and plant age. This occurs because, for most plant
      species, larger individuals are older individuals. This is a limitation because
      it prevents us from knowing whether insect community patterns are more dependent
      on traits associated with plant size, like resource quantity or plant apparency,
      or traits associated with plant age, like ontogenetic changes in phytochemistry.
      To separate these effects, we characterized galling insect communities on
      sagebrush (Artemisia tridentata)-a shrub in which age and size are not tightly
      correlated. We identified gall insects and recorded morphological measurements
      from 60 plants that varied separately in size and age. We found that plant size
      explained significantly more variation in insect gall abundance and species
      richness than did plant age. These results suggest that processes supporting the
      plant architecture hypothesis in this system are driven primarily by plant size
      and not plant age per se. Resource qualities associated with host-plant ontogeny
      may be less important than resource quantity in the assembly of herbivorous
      insect communities.

PMID- 26314055
TI  - Evaluating Weeds as Hosts of Tomato yellow leaf curl virus.
AB  - Bemisia tabaci (Gennadius) biotype B transmits Tomato yellow leaf curl virus
      (TYLCV), which affects tomato production globally. Prompt destruction of virus
      reservoirs is a key component of virus management. Identification of weed hosts
      of TYLCV will be useful for reducing such reservoirs. The status of weeds as
      alternate hosts of TYLCV in Florida remains unclear. In greenhouse studies, B.
      tabaci adults from a colony reared on TYLCV-infected tomato were established in
      cages containing one of four weeds common to horticultural fields in central and
      south Florida. Cages containing tomato and cotton were also infested with
      viruliferous whiteflies as a positive control and negative control, respectively.
      Whitefly adults and plant tissue were tested periodically over 10 wk for the
      presence of TYLCV using PCR. After 10 wk, virus-susceptible tomato plants were
      placed in each cage to determine if whiteflies descended from the original adults
      were still infective. Results indicate that Bidens alba, Emilia fosbergii, and
      Raphanus raphanistrum are not hosts of TYLCV, and that Amaranthus retroflexus is
      a host.

PMID- 26314056
TI  - Drilling-in and Chewing-out of Hosts by the Parasitoid Wasp Spalangia endius
      (Hymenoptera: Pteromalidae) When Parasitizing Musca domestica (Diptera:
      Muscidae).
AB  - Many organisms are protected from natural enemies by a tough exterior. Such
      protection is particularly important for immobile stages, such as pupae. The pupa
      of some insects is protected by a puparium, which is a shell formed from the
      exoskeleton of the last larval instar. However, the puparium of certain fly
      species is drilled through by adult females of the wasp Spalangia endius Walker.
      The female wasp then deposits an egg on the fly pupa within the puparium. After
      the wasp offspring finishes feeding on the fly pupa, it chews through the
      puparium to complete emergence. Despite the apparent toughness of the puparium,
      there was no detectable wear on the ovipositor of S. endius females even when
      females had been encountering fly pupae (Musca domestica L.) for weeks, and
      regardless of whether the pupae were large or old or both. Energy dispersive
      spectroscopy did not reveal any metal ions in the ovipositor's cuticle to account
      for this resistance against wear. Offspring of S. endius that chewed their way
      out of pupae also showed no detectable wear on their mandibles. Tests with a
      penetrometer showed that the force required to penetrate the center of a puparium
      was greater for larger and for older pupae; and an index of overall thickness was
      greater for large old pupae than for small old pupae. The lack of an effect of
      pupal size or age on wear may result from wasps choosing locations on the
      puparium that are easier to get through.

PMID- 26314057
TI  - Resource Effects on Solitary Bee Reproduction in a Managed Crop Pollination
      System.
AB  - Population density may affect solitary bee maternal resource allocation. The
      number of Megachile rotundata (F.), alfalfa leafcutting bee, females released for
      seed production of Medicago sativa L., alfalfa, may limit flower availability for
      nest provisioning. In turn, pollinator abundance also may affect crop yield. The
      M. sativa pollination system presents an opportunity to test for effects of
      density dependence and maternal manipulation on M. rotundata reproduction. A
      multiyear study was performed on M. sativa fields upon which M. rotundata
      densities were altered to induce low, medium, and high density situations.
      Numbers of adult bees and open flowers were recorded weekly; bee reproduction
      variables were collected once. Fields varied in plant performance for each site
      and year, and the intended bee densities were not realized. Therefore, the
      variable density index (DI) was derived to describe the number of female bees per
      area of flowers over the study period. As DI increased, percentages of pollinated
      flowers, established females, and healthy brood significantly increased, and the
      number of pollinated flowers per female and of dead or diseased brood
      significantly decreased. Sex ratio was significantly more female biased as DI
      increased. Overwintered offspring weights were similar regardless of DI, but
      significantly differed by year for both sexes, and for males also by field and
      year * field interaction. Overall, resource limitation was not found in this
      field study. Other density-dependent factors may have induced a bee dispersal
      response soon after bees were released in the fields that circumvented the need
      for, or impact of, maternal manipulation.

PMID- 26314058
TI  - A Landscape Analysis to Understand Orientation of Honey Bee (Hymenoptera: Apidae)
      Drones in Puerto Rico.
AB  - Honey bees [Apis mellifera L. (Apidae, Hymenoptera)] show spatial learning
      behavior or orientation, in which animals make use of structured home ranges for
      their daily activities. Worker (female) orientation has been studied more
      extensively than drone (male) orientation. Given the extensive and large flight
      range of drones as part of their reproductive biology, the study of drone
      orientation may provide new insight on landscape features important for
      orientation. We report the return rate and orientation of drones released at
      three distances (1, 2, and 4 km) and at the four cardinal points from an apiary
      located in Gurabo, Puerto Rico. We used high-resolution aerial photographs to
      describe landscape characteristics at the releasing sites and at the apiary.
      Analyses of variance were used to test significance among returning times from
      different distances and directions. A principal components analysis was used to
      describe the landscape at the releasing sites and generalized linear models were
      used to identify landscape characteristics that influenced the returning times of
      drones. Our results showed for the first time that drones are able to return from
      as far as 4 km from the colony. Distance to drone congregation area, orientation,
      and tree lines were the most important landscape characteristics influencing
      drone return rate. We discuss the role of landscape in drone orientation.

PMID- 26314059
TI  - Infestation of Caliothrips phaseoli (Thysanoptera: Thripidae) on Bean Cultivars
      Grown in the Winter, Rainy, and Dry Seasons in Brazil.
AB  - The present study aimed to identify common bean (Phaseolus vulgaris L.) cultivars
      less susceptible to Caliothrips phaseoli (Hood) in different growing seasons, to
      evaluate whether climatic conditions influence plant resistance to C. phaseoli
      infestation, and to investigate the preferred plant part for insect feeding.
      Eighteen common bean cultivars were evaluated in the winter season, and 19
      cultivars were assessed in the rainy and dry seasons, under field conditions in
      the municipality of Jaboticabal, state of Sao Paulo, Brazil. Infestation of C.
      phaseoli nymphs in the upper and lower parts of the beans plants was recorded at
      weekly intervals from 25 days after plant emergence (DAE) to 60 DAE. In the
      winter season, the cultivars 'IAC Galante,' 'IAC Centauro,' 'IAC Carioca Ete,'
      and 'IAC Formoso' had significantly lower number of thrips than the cultivar 'IAC
      Diplomata.' In the rainy season, the cultivars 'IAC Harmonia' and 'IPR Siriri'
      had the lowest thrips infestation, differing from the cultivars 'BRS Pontal' and
      'IAC Una.' The bean cultivars were equally susceptible to C. phaseoli in the dry
      season. The results suggest that C. phaseoli nymphs prefer to infest leaves of
      the lower part of bean plants, like most generalist herbivorous insects. In the
      winter and dry seasons, the highest thrips infestation was observed at 60 DAE,
      while in the rainy season, it was recorded from 32 to 46 DAE. Overall, C.
      phaseoli infestation on bean cultivars was not influenced by either temperature,
      relative humidity, or rainfall.

PMID- 26314060
TI  - An Extraordinary Host-Specific Sex Ratio in an Avian Louse (Phthiraptera:
      Insecta)--Chemical Distortion?
AB  - Distortions of sex ratios and sexual traits from synthetic chemicals have been
      well documented; however, there is little evidence for such phenomena associated
      with naturally occurring chemical exposures. We reasoned that chemical secretions
      of vertebrates could contribute to skewed sex ratios in ectoparasitic insects due
      to differences in susceptibility among the sexes. For example, among
      ectoparasitic lice the female is generally the larger sex. Smaller males may be
      more susceptible to chemical effects. We studied sex ratios of lice on two
      sympatric species of colonial seabirds. Crested auklets (Aethia cristatella)
      secrete a strong smelling citrus-like odorant composed of aldehydes while a
      closely related congener the least auklet (Aethia pusilla) lacks these compounds.
      Each auklet hosts three species of lice, two of which are shared in common. We
      found that the sex ratio of one louse species, Quadraceps aethereus (Giebel), was
      highly skewed on crested auklets 1:69 (males: females), yet close to unity on
      least auklets (1:0.97). We suggest that a host-specific effect contributes to
      this difference, such as the crested auklet's chemical odorant.

PMID- 26314061
TI  - Electroantennogram Responses and Field Trapping of Asian Cockroach (Dictyoptera:
      Blattellidae) with Blattellaquinone, Sex Pheromone of the German Cockroach
      (Dictyoptera: Blattellidae).
AB  - The Asian cockroach, Blattella asahinai Mizukubo, first introduced to Florida in
      1986, has been spreading throughout the southeastern United States. Populations
      can reach extremely high densities and cause damage to crops as well as become a
      nuisance in residential settings. Because the German cockroach, Blattella
      germanica L., is its closest extant relative, we characterized the B. asahinai
      male response to blattellaquinone, the sex pheromone of the German cockroach, in
      an effort to develop monitoring tools for B. asahinai. Electroantennogram (EAG)
      analysis was conducted on B. asahinai and B. germanica males and females, and
      revealed that the antennae of males of both species responded significantly more
      to blattellaquinone than females, and in both males and females absolute EAG
      responses of B. asahinai were greater than in B. germanica males and females,
      respectively. However, normalized male EAG response curves and ED50 values
      (effective dose to elicit 50% of maximal response) did not differ significantly
      between the two species. Results of field trapping experiments demonstrated that
      male B. asahinai were more attracted to blattellaquinone than any other life
      stage, and 10 MUg of blattellaquinone attracted the most males. These results
      suggest that blattellaquinone or a similar compound might be a component of the
      sex pheromone of B. asahinai females.

PMID- 26314062
TI  - Evaluating Predators and Competitors in Wisconsin Red Pine Forests for Attraction
      to Mountain Pine Beetle Pheromones for Anticipatory Biological Control.
AB  - Mountain pine beetle, Dendroctonus ponderosae Hopkins (Coleoptera:
      Curculionidae), is an irruptive tree-killing species native to pine forests of
      western North America. Two potential pathways of spread to eastern forests have
      recently been identified. First, warming temperatures have driven range expansion
      from British Columbia into Albertan jack pine forests that are contiguous with
      the Great Lakes region. Second, high temperatures and drought have fostered
      largescale outbreaks within the historical range, creating economic incentives to
      salvage killed timber by transporting logs to midwestern markets, which risks
      accidental introduction. We evaluated the extent to which local predators and
      competitors that exploit bark beetle semiochemicals would respond to D.
      ponderosae in Wisconsin. We emulated D. ponderosae attack by deploying lures
      containing synthetic aggregation pheromones with and without host tree compounds
      and blank control traps in six red pine plantations over 2 yr. Predator
      populations were high in these stands, as evidenced by catches in positive
      control traps, baited with pheromones of local bark beetles and were deployed
      distant from behavioral choice plots. Only one predator, Thanasimus dubius F.
      (Coleoptera: Cleridae) was attracted to D. ponderosae's aggregation pheromones
      relative to blank controls, and its attraction was relatively weak. The most
      common bark beetles attracted to these pheromones were lower stem and root
      colonizers, which likely would facilitate rather than compete with D. ponderosae.
      There was some, but weak, attraction of potentially competing Ips species. Other
      factors that might influence natural enemy impacts on D. ponderosae in midwestern
      forests, such as phenological synchrony and exploitation of male-produced
      pheromones, are discussed.

PMID- 26314063
TI  - Climate Warming May Threaten Reproductive Diapause of a Highly Eusocial Bee.
AB  - Climate changes are predicted to affect the diapause of many insect species
      around the world adversely. In this context, bees are of interest due to their
      pollination services. In southern Brazil, the highly eusocial bee species Plebeia
      droryana (Friese) (Hymenoptera: Apidae: Meliponini) exhibits reproductive
      diapause in response to the region's rigorous winters. That diapause is
      characterized by a temporary interruption in brood cell construction by nurse
      bees and egg-laying by the queen, regardless of other internal tasks underway in
      the nests. In this study, we evaluated whether P. droryana enter diapause under
      experimental conditions. P. droryana colonies were kept in a germination chamber,
      and the temperature was progressively reduced from 20 degrees C over a period of
      a few weeks until diapause was detected. Additionally, we also estimated the
      environmental conditions in the actual geographic range occupied by P. droryana
      and modeled it for predicted changes in climate up to the year 2080. Our findings
      indicate that P. droryana enter diapause between 10 and 8 degrees C. We also
      found that the current minimum winter temperature (10.1 degrees C, median) in the
      distributional range of P. droryana will probably rise (13.4 degrees C, median).
      Thus, if our experimental data are somewhat accurate, ~36% of the southern
      Brazilian P. droryana population may be active during the expected milder winter
      months in 2080. In this scenario, there may be a larger demand for pollen and
      nectar for that bee species. Greater conservation efforts will be required to
      preserve P. droryana populations and keep them viable in the coming decades.

PMID- 26314064
TI  - Temperature Characterization of Different Urban Microhabitats of Aedes albopictus
      (Diptera Culicidae) in Central-Northern Italy.
AB  - Aedes albopictus (Skuse) is an invasive mosquito species that has spread to many
      countries in temperate regions bordering the Mediterranean basin, where it is
      becoming a major public health concern. A good knowledge of the thermal features
      of the most productive breeding sites for Ae. albopictus is crucial for a better
      estimation of the mosquitoes' life cycle and developmental rates. In this
      article, we address the problem of predicting air temperature in three
      microhabitats common in urban and suburban areas and the air and water
      temperature inside an ordinary catch basin, which is considered the most
      productive breeding site for Ae. albopictus in Italy. Temperature differences
      were statistically proven between the three microhabitats and between the catch
      basin external and internal temperature. The impacts on the developmental rates
      for each life stage of Ae. albopictus were tested through a parametric function
      of the temperature, and the aquatic stages resulted as being the most affected
      using the specific temperature inside a typical catch basin instead of a generic
      air temperature. The impact of snow cover on the catch basin internal
      temperature, and consequently on the mortality of diapausing eggs, was also
      evaluated. These data can be useful to improve epidemiological models for a
      better prediction of Ae. albopictus seasonal and population dynamics in central
      northern Italian urban areas.

PMID- 26314065
TI  - Size-Dependent Realized Fecundity in Two Lepidopteran Capital Breeders.
AB  - Body size is correlated with potential fecundity in capital breeders, but size
      dependent functions of realized fecundity may be impacted by reproductive losses
      due to mating failure or oviposition time limitations (number of eggs remaining
      in the abdomen of females at death). Post-mortem assessment of adults collected
      in the field after natural death represents a sound approach to quantify how body
      size affects realized fecundity. This approach is used here for two Lepidoptera
      for which replicated field data are available, the spruce budworm Choristoneura
      fumiferana Clemens (Tortricidae) and bagworm Metisa plana Walker (Psychidae).
      Dead female budworms were collected on drop trays placed beneath tree canopies at
      four locations. Most females had mated during their lifetime (presence of a
      spermatophore in spermatheca), and body size did not influence mating failure.
      Oviposition time limitation was the major factor restricting realized fecundity
      of females, and its incidence was independent of body size at three of the four
      locations. Both realized and potential fecundity of female budworms increased
      linearly with body size. Female bagworms are neotenous and reproduce within a
      bag; hence, parameters related to realized fecundity are unusually tractable. For
      each of five consecutive generations of bagworms, mating probability increased
      with body size, so that virgin-dead females were predominantly small, least
      fecund individuals. The implication of size-dependent reproductive losses are
      compared for the two organisms in terms of life history theory and population
      dynamics, with an emphasis on how differential female motility affects the
      evolutionary and ecological consequences of size-dependent realized fecundity.

PMID- 26314066
TI  - A Predictive Degree Day Model for the Development of Bactericera cockerelli
      (Hemiptera: Triozidae) Infesting Solanum tuberosum.
AB  - Bactericera cockerelli (Sulc) (Hemiptera: Triozidae) is a pest of potato (Solanum
      tuberosum L.) that vectors the bacterium that putatively causes zebra chip
      disease in potatoes, 'Candidatus Liberibacter solanacearum.' Zebra chip disease
      is managed by controlling populations of B. cockerelli in commercial potato
      fields. Lacking an integrated pest management strategy, growers have resorted to
      an intensive chemical control program that may be leading to insecticide
      resistant B. cockerelli populations in south Texas and Mexico. To initiate the
      development of an integrated approach of controlling B. cockerelli, we used
      constant temperature studies, nonlinear and linear modeling, and field sampling
      data to determine and validate the degree day parameters for development of B.
      cockerelli infesting potato. Degree day model predictions for three different B.
      cockerelli life stages were tested against data collected from pesticide-free
      plots. The model was most accurate at predicting egg-to-egg and nymph-to-nymph
      peaks, with less accuracy in predicting adult-to-adult peaks. It is impractical
      to predict first occurrence of B. cockerelli in potato plantings as adults are
      present as soon cotyledons break through the soil. Therefore, we suggest
      integrating the degree day model into current B. cockerelli management practices
      using a two-phase method. Phase 1 occurs from potato planting through to the
      first peak in a B. cockerelli field population, which is managed using current
      practices. Phase 2 begins with the first B. cockerelli population peak and the
      degree day model is initiated to predict the subsequent population peaks, thus
      providing growers a tool to proactively manage this pest.

PMID- 26314067
TI  - Suspension of Egg Hatching Caused by High Humidity and Submergence in Spider
      Mites.
AB  - We tested the effects of high humidity and submergence on egg hatching of spider
      mites. In both the high humidity and submergence treatments, many Tetranychus and
      Panonychus eggs did not hatch until after the hatching peak of the lower humidity
      or unsubmerged controls. However, after humidity decreased or water was drained,
      many eggs hatched within 1-3 h. This was observed regardless of when high
      humidity or submergence treatments were implemented: either immediately after
      oviposition or immediately before hatching was due. Normal eyespot formation was
      observed in most eggs in the high humidity and submergence treatments, which
      indicates that spider mite embryos develop even when eggs are underwater.
      Therefore, delays in hatching are not caused by delayed embryonic development. A
      delay in hatching was always observed in Panonychus citri (McGregor) but was more
      variable in Tetranychus urticae Koch and Tetranychus kanzawai Kishida. The high
      humidity and submergence treatments affected but did not suppress larval
      development in these species. In contrast, many Oligonychus eggs died following
      the high humidity treatments. In Tetranychus and Panonychus spider mites,
      suspension of egg hatching may mitigate the adverse effects of rainfall.

PMID- 26314068
TI  - Suitability of Microtheca ochroloma (Coleoptera: Chrysomelidae) for the
      Development of the Predator Chrysoperla rufilabris (Neuroptera: Chrysopidae).
AB  - Microtheca ochroloma Stal, the yellowmargined leaf beetle, is one of the most
      destructive pests of crucifer vegetables on organic farms. Larvae of the green
      lacewing Chrysoperla rufilabris Burmeister have been observed preying on M.
      ochroloma, but no studies have evaluated the suitability of M. ochroloma as prey
      for C. rufilabris or the efficacy of this predator as a biological control agent
      of the pest. This study quantified the killing rate, developmental time, and
      survivorship of C. rufilabris when offered eggs and larvae of M. ochroloma at 10,
      15, 20, or 25 degrees C. Mean number of prey killed daily increased from 8.4 eggs
      and 4.0 larvae at 15 degrees C to 18.6 eggs and 10.2 larvae at 25 degrees C.
      However, predator larvae killed 78% fewer total eggs at 25 degrees C than at 15
      degrees C; total number of first-instar prey killed did not vary significantly
      with temperature. Mean developmental time of predator larvae decreased from 75.5
      d at 15 degrees C to 26.6 d at 25 degrees C when they were fed eggs, whereas it
      decreased from 54.0 d at 15 degrees C to 21.4 d at 25 degrees C when they were
      fed larvae. Predator survivorship was reduced by 80% at 15 degrees C and no
      larvae survived at 10 degrees C. We conclude that C. rufilabris can complete
      development on a diet of eggs of M. ochroloma, but its effectiveness to control
      M. ochroloma populations will be lessened during cool months, from November to
      April, when crucifers are produced in Florida and the beetle is actively
      developing, reproducing, and causing crop damage.

PMID- 26314069
TI  - Temperature- and Relative Humidity-Dependent Life History Traits of Phenacoccus
      solenopsis (Hemiptera: Pseudococcidae) on Hibiscus rosa-sinensis (Malvales:
      Malvaceae).
AB  - Phenacoccus solenopsis Tinsley (Hemiptera: Pseudococcidae), a worldwide
      distributive invasive pest, originated from the United States, and it was first
      reported in Guangdong province, China, in 2008. The effects of temperature and
      relative humidity (RH) on the life history traits of P. solenopsis on Hibiscus
      rosa-sinensis L. (Malvales: Malvaceae) were studied at seven constant
      temperatures (15, 20, 25, 27.5, 30, 32.5, and 35 degrees C) and three RHs (45,
      60, and 75%). The results showed that temperature, RH, and their interactions
      significantly influenced the life history traits of P. solenopsis. First instar
      was the most sensitive stage to extreme temperatures with very low survival rates
      at 15 and 35 degrees C. At 25-32.5 degrees C and the three RHs, the developmental
      periods of entire immature stage were shorter with values between 12.5-18.6 d.
      The minimum threshold temperature and the effective accumulative temperature for
      the pest to complete one generation were 13.2 degrees C and 393.7 degree-days,
      respectively. The percentage and longevity of female adults significantly
      differed among different treatments. It failed to complete development at 15 or
      35 degrees C and the three RHs. Female fecundity reached the maximum value at
      27.5 degrees C and 45% RH. The intrinsic rate for increase (r), the net
      reproductive rate (R0), and the finite rate of increase (lambda) reached the
      maximum values at 27.5 degrees C and 45% RH (0.22 d(-1), 244.6 hatched eggs, and
      1.25 d(-1), respectively). Therefore, we conclude that 27.5 degrees C and 45% RH
      are the optimum conditions for the population development of the pest.

PMID- 26314070
TI  - Phenotypic Variation and Sexual Size Dimorphism in Dichroplus elongatus
      (Orthoptera: Acrididae).
AB  - Patterns of body size evolution are of particular interest because body size can
      affect virtually all the physiological and life history traits of an organism.
      Sexual size dimorphism (SSD), a difference in body size between males and
      females, is a widespread phenomenon in insects. Much of the variation in SSD is
      genetically based and likely due to differential selection acting on males and
      females. The importance of environmental variables and evolutionary processes
      affecting phenotypeic variation in both sexes may be useful to gain insights into
      insect ecology and evolution. Dichroplus elongatus Giglio-Tos is a South American
      grasshopper widely distributed throughout Argentina, Uruguay, most of Chile, and
      southern Brazil. In this study, we analyzed 122 adult females of D. elongatus
      collected in eight natural populations from central-east Argentina. Females show
      large body size variation among the analyzed populations and this variation
      exhibits a strong relationship with fecundity. Our results have shown that larger
      females were more fecund than smaller ones. We found that ovariole number varied
      along a latitudinal gradient, with higher ovariole numbers in populations from
      warmer locations. A considerable female-biased SSD was detected. SSD for three
      analyzed morphometric traits scaled isometrically. However, SSD for thorax length
      displayed a considerable variation across the studied area, indicating a larger
      relative increase in female size than in male size in warmer environmental
      conditions.

PMID- 26314071
TI  - Direct Effects of Elevated CO2 Levels on the Fitness Performance of Asian Corn
      Borer (Lepidoptera: Crambidae) for Multigenerations.
AB  - Understanding direct response of insects to elevated CO2 should help to elucidate
      the mechanistic bases of the effects of elevated CO2 on interactions of insects
      with plants. This should improve our ability to predict shifts in insect
      population dynamics and community interactions under the conditions of climate
      change. Effects of elevated CO2 levels on the fitness-related parameters were
      examined for multigenerations in the Asian corn borer, Ostrinia furnacalis
      (Guenee). The larvae were allowed to feed on artificial diet, and reared in the
      closed-dynamic environment chambers with three CO2 levels (ambient, 550
      MUl/liter, and 750 MUl/liter) for six generations. In comparison with the ambient
      CO2 level, mean larval survival rate decreased 9.9% in 750 MUl/liter CO2 level,
      across O. furnacalis generations, and larval and pupal development times
      increased 7.5-16.4% and 4.5-13.4%, respectively, in two elevated CO2 levels.
      Pupal weight was reduced more than 12.2% in 750 MUl/liter CO2 level. Across O.
      furnacalis generations, mean food consumption per larva increased 2.7, 7.0% and
      frass excretion per larva increased 14.4, 22.5% in the two elevated CO2 levels,
      respectively, compared with ambient CO2 level. Elevated CO2 levels resulted in
      the decline mean across O. furnacalis generations in mean relative growth rate,
      but increased in relative consumption rate. These results suggested that elevated
      CO2 would reduce the fitness-related parameters such as higher mortality, lower
      pupal weight, and longer development times in long term. It also reduced the
      larval food digestibility and utilizing efficiency; in turn, this would result in
      increase of food consumption.

PMID- 26314072
TI  - Distribution of Bemisia tabaci Genetic Groups in India.
AB  - The whitefly Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) is a phloem
      feeding, economically important pest of crops worldwide. In addition to direct
      damage, it also vectors a number of plant viruses belonging to the family
      Geminiviridae. Its populations differ biologically with respect to insecticide
      resistance, virus transmission and host range. Therefore, understanding genetic
      variation among populations is important for management. We sequenced 850 bp of
      the mitochondrial COI (mtCOI) gene from B. tabaci populations surveyed across
      India. BLAST analysis of the mtCOI sequences generated in this study with
      sequences from the mtCOI dataset showed the presence of one invasive group,
      MEAM1, and eight other groups of B. tabaci in India. mtCOI sequence analyses
      showed the presence of Asia I, Asia I-India, Asia II-1, Asia II-5, Asia II-7,
      Asia II-8, and Asia II-11 genetic groups. We also found China-3 in a field in
      Birbhum district, West Bengal, India, suggesting a role of anthropogenic
      activities in the distribution of B. tabaci. Interestingly, more than one genetic
      group was found coexisting in the same field.

PMID- 26314073
TI  - Ecological Genetics and Host Range Expansion by Busseola fusca (Lepidoptera:
      Noctuidae).
AB  - The host plant range of pests can have important consequences for its evolution,
      and plays a critical role in the emergence and spread of a new pest outbreak.
      This study addresses the ecological genetics of the indigenous African maize stem
      borer, Busseola fusca (Fuller) (Lepidoptera: Noctuidae), in an attempt to
      investigate the evolutionary forces that may be involved in the recent host range
      expansion and establishment of this species in Ethiopian and southern African
      sugarcane. We used populations from Ethiopia, Zimbabwe, and South Africa to
      examine whether the host range expansion patterns shared by the Ethiopian and the
      southern African populations of B. fusca have evolved independently. Base-pair
      differences in the cytochrome oxidase I (COI) gene were used to characterize
      haplotype diversity and phylogenetic relationships. There were seven haplotypes
      among the 30 sequenced individuals collected on four host plant species from 17
      localities in the four countries. Of the seven COI haplotypes identified, the two
      major ones occurred in both sugarcane and maize. Genetic analyses revealed no
      detectable genetic differentiation between southern African B. fusca populations
      from maize and sugarcane (FST = 0.019; P = 0.24). However, there was strong
      evidence of variation in genetic composition between populations of the pest from
      different geographic regions (FST = 0.948; P < 0.001). The main implication of
      these findings is that the B. fusca populations in maize in southern Africa are
      more likely to shift to sugarcane, suggesting that ecological opportunity is an
      important factor in host plant range expansion by a pest.

PMID- 26314074
TI  - Inhibition of Helicoverpa zea (Lepidoptera: Noctuidae) Growth by Transgenic Corn
      Expressing Bt Toxins and Development of Resistance to Cry1Ab.
AB  - Transgenic corn, Zea mays L., that expresses the Bacillus thuringiensis (Bt)
      toxin Cry1Ab is only moderately toxic to Helicoverpa zea (Boddie) and has been
      planted commercially since 1996. Growth and development of H. zea was monitored
      to determine potential changes in susceptibility to this toxin over time. Small
      plots of corn hybrids expressing Cry1F, Cry1F * Cry1Ab, Cry1Ab * Cry3Bb1,
      Cry1A.105 * Cry2Ab2 * Cry3Bb1, Cry1A.105 * Cry2Ab2, and Vip3Aa20 * Cry1Ab *
      mCry3A were planted in both 2012 and 2013 inNorth and South Carolina with paired
      non-Bt hybrids from the same genetic background. H. zea larvae were sampled on
      three time periods from ears and the following factors were measured: kernel area
      injured (cm(2)) by H. zea larvae, larval number per ear, larval weight, larval
      length, and larval head width. Pupae were sampled on a single time period and the
      following factors recorded: number per ear, weight, time to eclosion, and the
      number that eclosed. There was no reduction in larval weight, number of insect
      entering the pupal stadium, pupal weight, time to eclosion, and number of pupae
      able to successfully eclose to adulthood in the hybrid expressing Cry1Ab compared
      with a non-Bt paired hybrid. As Cry1Ab affected these in 1996, H. zea may be
      developing resistance to Cry1Ab in corn, although these results are not
      comprehensive, given the limited sampling period, size, and geography. We also
      found that the negative impacts on larval growth and development were greater in
      corn hybrids with pyramided traits compared with single traits.

PMID- 26314080
TI  - Precision medicine in diffuse large B-cell lymphoma: hitting the target.

PMID- 26314081
TI  - Oxidative stress as a therapeutic perspective for ATM-deficient chronic
      lymphocytic leukemia patients.

PMID- 26314083
TI  - ADAM17 and CD56low CD16low NK cells.

PMID- 26314084
TI  - Response to comment on Multifunctional human CD56low CD16low NK cells are the
      prominent subset in bone marrow of both pediatric healthy donors and leukemic
      patients.

PMID- 26314085
TI  - Methodological and Statistical Quality in Research Evaluating Nutritional
      Attitudes in Sports.
AB  - The assessment of dietary attitudes and behaviors provides information of
      interest to sports nutritionists. Although there has been little analysis of the
      quality of research undertaken in this field, there is evidence of a number of
      flaws and methodological concerns in some of the studies in the available
      literature. This review undertook a systematic assessment of the attributes of
      research assessing the nutritional knowledge and attitudes of athletes and
      coaches. Sixty questionnaire-based studies were identified by a search of
      official databases using specific key terms with subsequent analysis by certain
      inclusion-exclusion criteria. These studies were then analyzed using 33 research
      quality criteria related to the methods, questionnaires, and statistics used. We
      found that many studies did not provide information on critical issues such as
      research hypotheses (92%), the gaining of ethics approval (50%) or informed
      consent (35%), or acknowledgment of limitations in the implementation of studies
      or interpretation of data (72%). Many of the samples were nonprobabilistic (85%)
      and rather small (42%). Many questionnaires were of unknown origin (30%),
      validity (72%), and reliability (70%) and resulted in low (<= 60%) response rates
      (38%). Pilot testing was not undertaken in 67% of the studies. Few studies dealt
      with sample size (2%), power (3%), assumptions (7%), confidence intervals (3%),
      or effect sizes (3%). Improving some of these problems and deficits may enhance
      future research in this field. 

PMID- 26314082
TI  - Consensus recommendations for the diagnosis and management of hemophagocytic
      lymphohistiocytosis associated with malignancies.
AB  - The hyperinflammatory syndrome hemophagocytic lymphohistiocytosis can occur in
      the context of malignancies. Malignancy-triggered hemophagocytic
      lymphohistiocytosis should be regarded separately from hemophagocytic
      lymphohistiocytosis during chemotherapeutic treatment, which is frequently
      associated with an infectious trigger. The substantial overlap between the
      features of hemophagocytic lymphohistiocytosis with features of neoplasms makes
      its identification difficult when it occurs in malignant conditions. To
      facilitate recognition and diagnostic workup, and provide guidance regarding the
      treatment of malignancy-associated hemophagocytic lymphohistiocytosis, consensus
      recommendations were developed by the Study Group on Hemophagocytic
      Lymphohistiocytosis Subtypes of the Histiocyte Society, an interdisciplinary
      group consisting of pediatric and adult hemato-oncologists and immunologists.

PMID- 26314086
TI  - Cycling Time Trial Performance 4 Hours After Glycogen-Lowering Exercise Is
      Similarly Enhanced by Recovery Nondairy Chocolate Beverages Versus Chocolate
      Milk.
AB  - Postexercise chocolate milk ingestion has been shown to enhance both glycogen
      resynthesis and subsequent exercise performance. To assess whether nondairy
      chocolate beverage ingestion post-glycogen-lowering exercise can enhance 20-km
      cycling time trial performance 4 hr later, eight healthy trained male cyclists
      (21.8 +/- 2.3y, VO2max = 61.2 +/- 1.4 ml.kg-1.min-1; M +/- SD) completed a series
      of intense cycling intervals designed to lower muscle glycogen (Jentjens &
      Jeukendrup, 2003) followed by 4 hr of recovery and a subsequent 20-km cycling
      time trial. During the first 2 hr of recovery, participants ingested chocolate
      dairy milk (DAIRYCHOC), chocolate soy beverage (SOYCHOC), chocolate hemp beverage
      (HEMPCHOC), low-fat dairy milk (MILK), or a low-energy artificially sweetened,
      flavored beverage (PLACEBO) at 30-min intervals in a double-blind,
      counterbalanced repeated-measures design. All drinks, except the PLACEBO (247 kJ)
      were isoenergetic (2,107 kJ), and all chocolate-flavored drinks provided 1-g
      CHO.kg body mass-1.h-1. Fluid intake across treatments was equalized (2,262 +/-
      148 ml) by ingesting appropriate quantities of water based on drink intake. The
      CHO:PRO ratio was 4:1, 1.5:1, 4:1, and 6:1 for DAIRYCHOC, MILK, SOYCHOC, and
      HEMPCHOC, respectively. One-way analysis of variance with repeated measures
      showed time trial performance (DAIRYCHOC = 34.58 +/- 2.5 min, SOYCHOC = 34.83 +/-
      2.2 min, HEMPCHOC = 34.88 +/- 1.1 min, MILK = 34.47 +/- 1.7 min) was enhanced
      similarly vs PLACEBO (37.85 +/- 2.1) for all treatments (p = .019) These data
      suggest that postexercise macronutrient and total energy intake are more
      important for same-day 20-km cycling time trial performance after glycogen
      lowering exercise than protein type or protein-to-carbohydrate ratio. 

PMID- 26314087
TI  - Gender Differences in Physical Activity Levels of Older People With Type 2
      Diabetes Mellitus.
AB  - BACKGROUND: Physical activity (PA) is important in managing Type 2 Diabetes
      Mellitus (T2DM). This study aimed to determine 1) the number of daily steps taken
      by older people with T2DM, 2) if T2DM is associated with taking fewer steps per
      day and less likelihood of meeting PA guidelines, and 3) whether these
      associations are modified by age or gender. METHODS: PA was obtained by pedometer
      from 2 cohorts of older adults with and without T2DM. Multivariable regression
      was used to determine associations between T2DM, mean steps per day and meeting a
      guideline equivalent (7 100 steps per day). RESULTS: There were 293 participants
      with T2DM (mean age 67.6 +/- 6.8 years) and 336 without T2DM (mean age 72.1 +/-
      7.1 years). In women, T2DM was associated with fewer mean steps per day (beta = 
      1306.4; 95% CI -2052.5, -560.3; P = .001) and not meeting the PA guidelines (OR
      0.51; 95% CI 0.28, 0.92; P = .03). Associations were not significant in men (P >
      .05). Only 29.7% of those with T2DM and 33.3% of those without T2DM met PA
      guidelines. CONCLUSIONS: Greater focus is needed on how to maintain and increase
      PA in older age with particular focus on women with T2DM.

PMID- 26314088
TI  - Lower Extremity Muscular Strength and Leukocyte Telomere Length: Implications of
      Muscular Strength in Attenuating Age-Related Chronic Disease.
AB  - OBJECTIVE: Leukocyte telomere length (LTL) shortening is characteristic of aging
      and is associated with morbidity and mortality, independent of age. Research
      demonstrates that lower extremity muscular strength is associated with mobility,
      morbidity and mortality; however, no study, to our knowledge, had examined the
      association between lower extremity muscular strength and LTL, which was the
      purpose of this brief study. METHODS: Data from the 1999-2002 NHANES was used (N
      = 2410; 50-85 years). Peak isokinetic knee extensor strength (IKES) was
      objectively measured with LTL assessed from a blood sample. RESULTS: After
      adjustments, for every 50 N increase in IKES, participants had a 9% reduced odds
      (P = .04) of being in the 1st (vs. 4th) LTL quartile. DISCUSSION: Lower extremity
      muscular strength is associated with LTL, suggesting a possible mechanism through
      which lower extremity muscular strength may be associated with morbidity and
      mortality.

PMID- 26314089
TI  - Dynamic Characteristic Analysis of Spinal Motor Control Between 11- and 15-Year
      Old Children.
AB  - Spinal motor control can provide substantial insight for the causes of spinal
      musculoskeletal disorders. Its dynamic characteristics however, have not been
      fully investigated. The objective of this study is to explore the dynamic
      characteristics of spinal motor control via the fractional Brownian motion
      mathematical technique. Spinal curvatures and repositioning errors of different
      spinal regions in 64 children age 11- or 15-years old during upright stance were
      measured and compared for the effects of age and gender. With the application of
      the fractional Brownian motion analytical technique to the changes of spinal
      curvatures, distinct persistent movement behaviors could be determined, which
      could be interpreted physiologically as open-loop behaviors. Moreover, it was
      found that the spinal motor control of 15-year-old children was better than that
      of 11-year-old children with smaller repositioning error and less curvature
      variability as well as shorter response time and smaller curvature deformation. 

PMID- 26314091
TI  - Are Motor Adjustments Quick Because They Don't Require Detection or Because They
      Escape Competition?

PMID- 26314090
TI  - Error Detection is Critical for Visual-Motor Corrections.
AB  - The target article (Smeets, Oostwoud Wijdenes, & Brenner, 2016) proposes that
      short latency responses to changes in target location during reaching reflect an
      unconscious, continuous, and incremental minimization of the distance between the
      hand and the target, which does not require detection of the change in target
      location. We, instead, propose that short-latency visuomotor responses invoke
      reflex- or startle-like mechanisms, an idea supported by evidence that such
      responses are both automatic and resistant to cognitive influences. In addition,
      the target article fails to address the biological underpinnings for the range of
      response latencies reported across the literature, including the circuits that
      might underlie the proposed sensorimotor loops. When considering the range of
      latencies reported in the literature, we propose that mechanisms grounded in
      neurophysiology should be more informative than the simple information processing
      perspective adopted by the target article. 

PMID- 26314092
TI  - [In Process Citation].

PMID- 26314093
TI  - Medical Devices; Immunology and Microbiology Devices;   Classification of
      Clostridium Difficile Toxin Gene Amplification Assay. Final order.
AB  - The Food and Drug Administration (FDA) is classifying Clostridium difficile (C.
      difficile) toxin gene amplification assay into class II (special controls). The
      Agency is classifying the device into class II (special controls) in order to
      provide a reasonable assurance of safety and effectiveness of the device.

PMID- 26314094
TI  - [Pollution of Halogenated Polycyclic Aromatic Hydrocarbons in Atmospheric
      Particulate Matters of Shenzhen].
AB  - Concentrations of halogenated polycyclic aromatic hydrocarbons ( HPAHs) in
      atmospheric PM10 and PM2.5 samples collected from Shenzhen were determined using
      GC-MS. Total concentrations of nine HPAHs in atmospheric PM10 and PM2.5 samples
      ranged from 118 to 1,476 pg . m(-3) and 89 to 407 pg . m(-3), respectively. In
      PM10 and PM(2.5) samples, the concentration of 9-BrAnt was the highest, followed
      by 7-BrBaA and 9, 10-Br2Ant. Seasonal levels of total HPAHs in atmospheric PM10
      and PM2.5 samples in Shenzhen decreased in the following order: winter > autumn >
      spring > summer, whereas concentrations of individual HPAHs showed different
      seasonal levels. Meteorological conditions, including temperature, precipitation,
      and relative humidity, might be important factors affecting the seasonal levels
      of HPAHs in atmospheric PM10 and PM2.5 In addition, there were significant
      correlations between concentrations of HPAHs and parent PAHs. Finally, the toxic
      equivalency quotients (TEQs) of HPAHs were estimated. The TEQs of HPAHs in
      atmospheric PM10 and PM2.5 samples ranged from 17.6 to 86.2 pg . m(-3) and 14.6
      to 70.4 pg . m(-3), respectively. Among individual HPAHs, 7-BrBaA contributed
      greatly to the total TEQs of HPAHs. Our results indicated that the total TEQs of
      HPAHs were lower than parent PAHs in atmospheric PM10 and PM2.5 samples in
      Shenzhen.

PMID- 26314095
TI  - [Emission Characteristics of VOCs from Typical Restaurants in Beijing].
AB  - Using the EPA method, emission of volatile organic compounds (VOCs) , sampled
      from barbecue, Chinese and Western fast-food, Sichuan cuisine and Zhejiang
      cuisine restaurants in Beijing was investigated. VOCs concentrations and
      components from different cuisines were studied. The results indicated that based
      on the calibrated baseline ventilation volume, the VOCs emission level from
      barbecue was the highest, reaching 12.22 mg . m(-3), while those from fast-food
      of either Chinese or Western, Sichuan cuisine and Zhejiang cuisine were about 4
      mg . m(-3). The components of VOCs from barbecue were different from those in the
      other cuisines, which were mainly propylene, 1-butene, n-butane, etc. The non
      barbecue cuisines consisted of high concentration of alcohols, and Western fast
      food contained relatively high proportion of aldehydes and ketones organic
      compounds. According to emission concentration of baseline ventilation volume,
      barbecue released more pollutants than the non-barbecue cuisines at the same
      scale. So, barbecue should be supervised and controlled with the top priority.

PMID- 26314096
TI  - [Characteristics Analysis of Sulfur Dioxide in Pearl River Delta from 2006 to
      2010].
AB  - Based on the in-situ SO2 observation dataset from 2006 to 2010 in Pearl River
      Delta(PRD) , the temporal characteristics of SO2 are analyzed. The results show
      that the annual average volume fraction of surface SO2 in 2010 declines to a
      level below average values in recent years, with reducing the frequency of high
      concentration episodes occurring. The seasonal, monthly and diurnal
      characteristics of surface SO2 are influenced by particular weather conditions in
      the PRD. The Probability Distribution Function(PDF) of surface SO2 volume
      fraction are complicated. The PDF is different every month maybe caused by the
      variation of the seasonal factors.

PMID- 26314097
TI  - [Comparison Test Between PM2.5 Continuous Monitoring System and Manual Sampling
      Analysis for PM2.5 in Ambient Air].
AB  - According to the U. S. EPA performance index and detection methods for comparison
      test of PM2.5 continuous monitoring system, in combination of the current related
      technical specifications in China, 4 types of typical imported and domestic PM2.5
      continuous monitoring system with two different principles were tested and
      compared to the manual sampling measurement (gravimetric method) in spring,
      summer, autumn and winter. This research determined the quality control
      requirements ( parallelism of manual sampling measurement results <= 5 ug . m(-3)
      or 5%), the technical index (slope of linearity regression equation 1 +/- 0.15;
      intercept 0 +/- 10; correlation coefficient >= 0.95), and corresponding detection
      methods of reference method comparison test to PM2.5 continuous monitoring
      system, which meets the requirement of current environmental quality status and
      environmental monitoring and management in China. It also provided technical
      means and method of quality control for effective use and data quality of PM2.5
      continuous monitoring system in China.

PMID- 26314098
TI  - [Determination and Emission of Condensable Particulate Matter from Coal-fired
      Power Plants].
AB  - The sampling-analysis method for CPM of stationary source was established and the
      sampling device was developed. The determination method was compared with EPA
      method 202 and applied in real-world test in coal-fired power plants. The result
      showed the average CPM emission concentration in the coal-fired power plant was
      (21.2 +/- 3.5) mg . m(-3) while the FPM was (20.6 +/- 10.0) mg . m(-3) during the
      same sampling period according to the method in the national standard. The high
      efficiency dust removal device could efficiently reduce FPM emission but showed
      insignificant effect on CPM. The mass contribution of CPM to TPM would rise after
      high-efficiency dust removal rebuilding project, to which more attention should
      be paid. The condensate contributed 68% to CPM mass while the filter contributed
      32%, and the organic component contributed little to CPM, accounting for only 1%.

PMID- 26314099
TI  - [Potential Carbon Fixation Capability of Non-photosynthetic Microbial Community
      at Different Depth of the South China Sea and Its Response to Different Electron
      Donors].
AB  - The seawater samples collected from many different areas with different depth in
      the South China Sea were cultivated using different electron donors respectively.
      And the variation in the potential carbon fixation capability ( PCFC ) of non
      photosynthetic microbial community (NPMC) in seawater with different depth was
      determined after a cycle of cultivation through the statistic analysis. In
      addition, the cause for the variation was clarified through analyzing key gene
      abundance regarding CO2 fixation and characteristics of seawater with different
      depth. The result showed that the PCFCs of NPMC in seawater with different depth
      were generally low and had no significant difference when using NaNO2 as the
      electron donor. The PCFC of NPMC in surface seawater was higher than that in deep
      seawater when using H2 as the electron donor, on the contrary, the PCFC of NPMC
      in deep seawater was higher than that in surface seawater when using Na2S2O3 as
      the electron donor. The abundance of the main CO2 fixation gene cbbL in surface
      seawater was higher than that in deep seawater while the cbbM gene abundance in
      deep seawater was higher than that in surface seawater. Most hydrogen-oxidizing
      bacteria had the cbbL gene, and most sulfur bacteria had the cbbM gene. The
      tendency of seawater cbbL/cbbM gene abundance with the change of depth revealed
      that there were different kinds of bacteria accounting for the majority in NPMC
      fixing CO2 at different depth of ocean, which led to different response of PCFC
      of NPMC at different depth of the sea to different electron donors. The
      distributions of dissolved oxygen and inorganic carbon concentration with the
      change of the depth of the sea might be an important reason leading to the
      difference of NPMC structure and even the difference of PCFC at different depth
      of the sea.

PMID- 26314100
TI  - [Remote Sensing Estimation of Chlorophyll-a Concentration in Inland Lakes Based
      on GOCI Image and Optical Classification of Water Body].
AB  - Chlorophyll-a as one of the important water quality parameters is often used as a
      measure of the level of water eutrophication. The 326 measured data collected
      from Lake Taihu and Lake Dongting were classified based on their measured values
      of remote sensing reflectance spectra using an automatic clustering algorithm-two
      step method, and three water types were finally classified. According to the
      location and width of GOCI satellite bands, the specific algorithm to estimate
      chlorophyll-a concentration for different water body types was developed. The
      bands at 490 nm and 555 nm were used for water body type I , while bands at 660
      nm and 443 nm were selected for water body type II and bands at 745 nm and 680 nm
      were applied for water body type III. The accuracy assessment showed that the
      mean relative error decreased from 49. 78% to 38. 91% , 24. 19% and 22. 90% for
      water body type I , II and III, respectively, while the root mean square error
      decreased from 14.10 ug . L(-1) to 4.87 ug . L(-1), 8.13 ug . L(-1) and 11.66 ug
      . L(-1) for water body type I, II and III, respectively. The overall mean
      relative error decreased from 49. 78% to 29. 59% after classification, while the
      overall root mean square error was reduced from 14.10 ug . L(-1) to 9.29 ug . L(
      1) after classification. The retrieval accuracy was significantly improved after
      classification. The chlorophyll-a concentration in Lake Taihu was retrieved using
      the GOCI image on May 13, 2013. The results showed that there was a significantly
      diurnal variation in the concentration of chllorophyll-a on May 13, 2013, and the
      regions with higher chlorophyll-a concentration were mainly distributed in the
      Zhushan Bay, Meiliang Bay and Gonghu Bay, while the regions with lower values
      were mainly located in the centre of the lake and the southern region. The
      chlorophyll-a concentration reduced significantly after 10:00 in the southwestern
      region of Lake Taihu. This method of retrieving, after classification played an
      important role in improving the model retrieval accuracy of case 2 water.

PMID- 26314101
TI  - [Hydrochemical Characteristics and Sources of Qingshuijiang River Basin at Wet
      Season in Guizhou Province].
AB  - According to the ion content and chemical characteristic analysis of
      Qingshuijiang River water during wet season, the result shows that the chemical
      composition of the river water is dominated by Ca2+, HCO(3-); Mg2+, and SO4(2-).
      The TDS concentration (213.96 mg . L(-1)) is significantly higher than the
      average value of rivers worldwide. Seawater correction approach (Cl(-) normalized
      seawater ratios) was applied to estimate the contribution proportions of local
      precipitation to the solutes, and it is found that the contribution ratio of
      precipitation (2.23%) is lower than the average value (3%) of global catchments.
      Furthermore, Gibbs graph combining major ion element ratio analysis indicates
      that the catchment hydrochemistry is mainly originated from carbonate rock
      weathering, which becomes increasingly distinct as the river goes downstream.
      Both carbonic acid and sulfuric acid play crucial roles in the chemical
      weathering. Ion source analysis demonstrates that Ca2+, Mg2+, HCO3- are mainly
      derived from chemical weathering of carbonate mineral (Dolomite and Calcite);
      Na+, K+ and Cl- are primarily contributed by silicate mineral weathering; SO4(2-)
      and NO3- stemmed are mainly from acid atmospheric deposition and from urban
      sewage input. Anthropogenic analysis suggests that the chemical composition of
      Qingshuijiang River is greatly impacted by the upriver industrial and mining
      enterprises activities.

PMID- 26314102
TI  - [Temporal-spatial Variation and Source Identification of Hydro-chemical
      Characteristics in Shima River Catchment, Dongguan City].
AB  - Shima River catchment is of strategic importance to urban water supply in
      Dongjiang portable water source area. To investigate the hydro-chemical
      characteristics of Shima River, 39 river water samples were collected in
      February, June and November, 2012 to analyze the major ions (K+, Na+, Ca2+, Mg2+,
      Cl-, SO4(2-) , HCO3-) and nutritive salts (PO4(3-), NO3- and NH4+) and to discuss
      the temporal-spatial variation and controlling factors of hydro-chemical
      composition, relative sources identification of varied ions was performed as
      well. The results showed that the hydro-chemical composition exhibited
      significant differences in different periods. The average concentration of total
      dissolved solid ( TDS) and nutritive salts in different investigated periods
      followed the decreasing order of November > February > June. The dominant anion
      of Shima River was HCO3-, and Na+ + K+ were the major cations in February and
      November which were changed to Ca2+ in June, the hydro-chemical types were
      determined as HCO(3-)-Na+ and HCO(3-)- Ca2+ in dry (February and November) and
      rainy (June) seasons, respectively. Spatial variations of concentration of
      nutritive salts were mainly affected by the discharges of N- and P-containing
      waste water resulted from human activities. The ratio between N and P of water
      sample (R7) was 18.4:1 which boosted the "crazy growth" of phytoplankton and led
      to severe eutrophication. According to Gibbs distribution of water samples,
      dissolution of hydatogenic rocks was the primary factor to control the major
      cations of river water in dry season, however, the hydro-chemical composition was
      significantly affected by the combination of hydatogenic and carbonate rocks in
      rainy season. The deposition of sea-salts contributed less to chemical substances
      in river. Correlation analysis revealed that K+, Na+, Mg2+, Cl- and SO4(2-) were
      partly derived from the application of fertilizer and the discharge of industrial
      effluent; Waste water of poultry feeding and sanitary wastewater transported
      large quantities of NH(4+)-N, PO4(3-)-P and NO(3-)-N into the river.

PMID- 26314103
TI  - [Response and Control Factors of Groundwater to Extreme Weather, Jiguan Cave,
      Henan Province, China].
AB  - Geochemical dynamics of cave water were monitored to unveil its variation and
      controlling factors from October 2009 to December 2013 in Jiguan Cave,west of
      Henan province,southeastern coast of the loess plateau. The results showed that:
      (1) the hydrochemical types of the cave water are HCO(3-)-Ca(2+)-Mg2+ and HCO(3-)
      Mg(2+)-Ca2+. HCO(3-) are over 80% of the anions, Ca2+ and Mg2+ are the dominate
      cations, and ground river keeping in erosion and pool water drips in deposition
      all the year. (2) Dripping water and pool water in Ji guan cave can respond
      perfectly to the change of external climate environment, which geochemistry
      indexes possess the extraordinary seasonal effects. (3) The concentration changes
      of the Ca2+, Mg2+ , SO4(2-) responded sensitively to annual precipitation change.
      Ca2+, Mg2+, SO4(2-) rise in waterlogging year and fall in drought year. Because
      HCO(3-) controlled by CO2 concentration. HCO(3-) concentration showed a
      unconspicuous response to the change of external climate environment. (4) The
      concentration changes of Ca2+, Mg2+, SO4(2-) have no obvious seasonal variation
      and showed a unconspicuous response to the change of external climate
      environment.

PMID- 26314104
TI  - [Impact of Rocky Desertification Treatment on Underground Water Chemistry and
      Dissolved Inorganic Carbon Isotope in Karst Areas].
AB  - Five springs representing different land-use types and different karst rocky
      desertification treatment models were chosen at the Huajiang Karst Rocky
      Desertification Treatment Demonstration Site in Guanling-Zhenfeng Counties in
      Guizhou, to analyze the features of underground water chemistry and dissolved
      inorganic carbon isotopes (delta13C(DIC)) and reveal the effect of rocky
      desertification treatment on karstification and water quality. It was found that,
      the underground water type of the research area was HCO3-Ca; the water quality of
      the springs which were relatively less affected by human activities including
      Shuijingwan Spring (SJW) , Gebei Spring (GB), and Maojiawan Spring (MJW) was
      better than those relatively more affected by human activities including Diaojing
      Spring (DJ) and Tanjiazhai Spring (TJZ) , the main ion concentrations and
      electrical conductivity of which were higher; pH, SIc and pCO2 were sensitive to
      land-use types and rocky desertification treatment, which could be shown by the
      higher pH and SIc and lower pCO2 in MJW than those in the other four springs;
      (Ca(2+) + Mg2+)/HCO(3-) of SJW, MJW and GB were nearly 1:1, dominated by
      carbonate rock weathering by carbon acid, while the (Ca(2+) + Mg2+) of DJ and TJZ
      was much higher than HCO3-, suggesting that sulfate and nitrate might also
      dissolve carbonate rock because of the agricultural activities; delta13C(DIC) was
      lighter in wet season because of the higher biological activities; the average
      delta13C(DIC) was in the order of DJ (-12.79 per thousand) < SJW (-12.48 per
      thousand) < GB (-10.76 per thousand)) < MJW (-10.30 per thousand) < TJZ (-6.70
      per thousand), which demonstrated that delta13C(DIC) would be heavier after rocky
      desertification and lighter after the rocky desertification are treated and
      controlled.

PMID- 26314105
TI  - [Difference of Karst Carbon Sink Under Different Land Use and Land Cover Areas in
      Dry Season].
AB  - In order to identify the distinction of soil CO2 consumed by carbonate rock
      dissolution, Baishuwan spring, Lanhuagou spring and Hougou spring were selected
      as objects to monitor the hydrochemistry from November 2013 to May 2014. The
      results showed that the highest HCO3- concentration was observed in Baishuwan
      spring which is covered by pine forest, while the lowest HCO3- concentration was
      observed in Hougou spring which is mainly covered by cultivated land. In
      Baishuwan spring, HCO3- was mainly derived from carbonic acid dissolving
      carbonate rock and the molar ratio between Ca(2+) + Mg2+ and HCO3- was close to
      0. 5; while the molar ratio between Ca(2+) + Mg2+ and HCO3- exceeded 0.5 because
      the carbonate rock in Lanhuagou spring and Hougou spring was mainly dissolved by
      nitric acid and sulfuric acid. Because of the input of litter and the fact that
      gas-permeability of soil was limited in Baishuwan spring catchment, most of soil
      CO2 was dissolved in infiltrated water and reacted with bedrock. However, in
      Lanhuagou spring catchment and Hougou spring catchment, porous soil made soil CO2
      easier to return to the atmosphere in the form of soil respiration. Therefore, in
      order to accurately estimate karst carbon sink, it was required to clarify the
      distinction of CO2 consumption by carbonate rock dissolution under different land
      use and land cover areas.

PMID- 26314106
TI  - [Vertical Migration Characteristics of Organochlorine Pesticides in Overlying
      Soil in Karst Terranes and Its Impact on Groundwater].
AB  - Five soil profiles and four typical epikarst springs were selected in Nanchuan
      District, Chongqing Municipality as objects of the study on vertical migration of
      organochlorine pesticides (OCPs) in the soils and its impact on groundwater. OCPs
      in soil and epikarst spring water samples were quantitatively analyzed by gas
      chromatography. The results showed that HCHs and DDTs were detected in all the 5
      soil profiles, varying in the range of 0.77-18.3 and 0.34-226 ng . g(-1), and
      averaging 5.16 and 16 ng . g(-1) in concentration, respectively. The highest
      concentrations of HCHs and DDTs were found in the subsoil (10-40 cm) in most
      sampling sites. The detection ratios of HCHs and DDTs in four springs were 100%.
      The concentrations of HCHs and DDTs fluctuated greatly in epikarst spring water
      during the one-year observation, and the concentration ranged from 2.09 to 60.1
      and from N. D. to 79.8 ng . L(-1), with a mean value of 12 and 9.16 ng . L(-1),
      respectively. The concentrations of HCHs and DDTs in Hougou, Baishuwan and
      Lanhuagou spring in rainy season were all. higher than those in dry season in
      these three epikarst springs. There were no good corresponding relationship
      between HCHs and DDTs contents in spring water and those in corresponding spring
      catchment soil. TOC, soil water content, clay content and pH all inhibited the
      vertical migration of OCPs in Hougou spring catchment, which led to the lowest
      content of OCPs in spring water, although the OCPs content in Hougou spring
      catchment soils was the highest in the four spring catchments. However, the four
      factors didn't inhibit the vertical migration of OCPs in Shuifang spring
      catchment, which led to higher OCPs content in spring water, although the OCPs
      content in spring catchment soils was the lowest in the four spring catchments.

PMID- 26314107
TI  - [Pollution Status and Migration of Mercury in the Sediments of Nansi Lake in
      Shandong Province].
AB  - The content of mercury and fractions were determined, in order to discuss the
      pollution situation and migration ability of mercury in inflow rivers and surface
      sediments of Nansi Lake. The average content of mercury in the sediments of the
      Nansi Lake was 0.046 mg . kg(-1), significantly higher than the environmental
      background values, which showed that Nansi Lake suffered from mercury pollution.
      Mercury in sediments existed mainly in the residual fraction, accounting for 65.
      15%. The proportion of non-residual fractions was relatively small, in the order
      of organic bound fraction (30.61%), extractable fraction (2.93%), and Fe/Mn oxide
      (1.31%). The spatial change of non-residual fractions was that Weishan Lake and
      Nanyang Lake had higher non-residual mercury content than Zhaoyang Lake and
      Dushan Lake, and the non-residual mercury had a certain potential ecological harm
      on Weishan Lake and Nanyang Lake. From the horizontal view, the mercury content
      in the surface sediments of Nansi Lake had visible difference and the pollution
      degree was different among sub-lakes, so horizontal migration of mercury was
      obvious. Vertically, the mercury content showed a trend of increasing from the
      bottom to the top in core sediments, which might be associated with social and
      economic conditions in different periods.

PMID- 26314108
TI  - [Response of Sediment Micro Environment and Micro Interface to Physical
      Disturbance Intensity Under the Disturbance of Chironomus plumosus].
AB  - The response of sediment micro environment and micro intertace to physical
      disturbance intensity under the physical and Chironomus plumosus disturbance was
      investigated by means of sediment Rhizon samplers and Unisense micro sensor
      system. The sediment and overlying water were taken from Meiliang bay of Taihu
      Lake. The results showed that the OPD reached up to 12.1 mm under the high
      intensity (240 r . min(-1)), while it was higher than 3. 8. mm under low
      intensity (60 r . min(-1)). The TOE, the difference of TOE and DOE, OPD, ORP and
      the difference of DO spatial distribution were all positively correlated with the
      physical disturbance intensity. The increasing magnitude and range of pH as well
      as the decreasing magnitude and range of ferrous followed the same response
      tendency. Within the 0-6 cm sediment, the water content and porosity as well as
      the microbial activity at the same depth increased with the increase of physical
      disturbance intensity. In addition, the degree of response of the above
      parameters to the physical disturbance intensity was weakened with the increase
      of sediment depth. It was suggested that Chironomus plumosus dug more and deeper
      galleries under high intensity physical disturbance. Therefore, the sediment
      micro environment and micro interface were transformed in the vertical direction
      of the sediment.

PMID- 26314109
TI  - [Characteristics of Atmospheric Nitrogen Wet Deposition and Associated Impact on
      N Transport in the Watershed of Red Soil Area in Southern China].
AB  - In this study, Qianyanzhou Xiangxi River Basin in the rainy season was monitored
      to measure different nitrogen form concentrations of rainfall and rainfall-runoff
      process, in order to explore the southern red soil region of nitrogen wet
      deposition characteristics and its influence on N output in watershed. The
      results showed that there were 27 times rainfall in the 2014 rainy season,
      wherein N wet deposition load reached 43.64-630.59 kg and N deposition flux were
      0.44-6.43 kg . hm(-2), which presented a great seasonal variability. We selected
      three rainfall events to make dynamic analysis. The rainfall in three rainfall
      events ranged from 8 to 14mm, and the deposition load in the watershed were from
      18.03 to 41.16 kg and its flux reached 0.18 to 0.42 kg . hm(-2). Meanwhile, this
      three rainfall events led to 4189.38 m3 of the total runoff discharge, 16.72 kg
      of total nitrogen (TN) load and 4.64 kg . hm(-2) of flux, wherein dissolved total
      nitrogen (DTN) were 9.64 kg and 2.68 kg . hm(-2), ammonium-nitrogen (NH(4+)-N)
      were 2.93 kg and 0.81 kg . hm(-2), nitrate-nitrogen (NO(3-)-N) were 5.60 kg and
      1.56 kg . hm(-2). The contribution rate of N wet deposition to N output from
      watershed reached 56%-94% , implying that the rainfall-runoff had tremendous
      contribution to N loss in this small watershed. The concentrations of TN in water
      had exceeded 1.5 mg . L(-1) of eutrophication threshold, which existed an
      eutrophication potential.

PMID- 26314110
TI  - [Effect of Different Purple Parent Rock on Removal Rates of Nitrogen, Phosphorus
      and Organics in Landscape Water].
AB  - In order to understand the impacts of physicochemical properties of purple parent
      rock on the removal rates of nitrogen, phosphorus and organics in landscape water
      systems, four types of purple parent rocks including Peng-lai-zhen Formation (S1)
      , Sha-xi-miao Formation (S2) , Fei-xian-guan Formation (S3) and Sui-ning
      Formation (S4) , which distribute widely in Chongqing, were selected and
      autoclaved, and added to unsterile landscape water collected from Chong-de Lake
      in Southwest University, and the landscape water only was used as control. And
      several indicators such as total nitrogen and phosphorus and so on of every
      disposal were investigated periodically. The results indicated that: (1) The
      highest removal rates of total nitrogen, total phosphorus and Ammonia nitrogen
      were observed in Sl, which were 45.1%, 62.3% and 90%, respectively; the highest
      removal rate of COD was 94.5% in S4; the ammonia nitrogen content in the purple
      parent rocks was not obviously changed before and after the experiments, which
      indicated that the adsorption of ammonia nitrogen on purple parent rock surface
      was not the main reason for the decrease of ammonia nitrogen in water. (2)
      Arsenate had inhibitory effect on the sulfate-reducing bacteria, while copper and
      magnesium had promoting effect on gram-negative bacteria. (3) The microbial
      diversity was positively correlated to total nitrogen in water. (4) Based on the
      PCA analyses of microbial community structure and environmental factors, the
      mineral elements released from parent rock affected the structure and composition
      of microbial community in the test water, and then influenced the removal rates
      of nitrogen, phosphorus and organics in water systems.

PMID- 26314111
TI  - [Effects of Litchi chinensis Defoliation on Growth and Photosynthesis of
      Microcystis aeruginosa].
AB  - The growth and physiology of bloom-forming cyanobacterium Microcystis aeruginosa
      were determined by the pulse amplitude modulated fluorimetry when exposed to
      different concentrations of Litchi chinensis defoliation extract for 15 d. The
      growth, maximal efficiency (Fv/Fm), effective quantum yield (YII) of PSII
      photochemistry, photosynthesis efficiency (alpha) , maximum electron transport
      rate (rETRmax) and light saturation coefficient (Ik) were used to evaluate the
      growth and photosynthesis in M. aeruginosa. It was found that the extract of L.
      chinensis defoliation stored for 5 days significantly inhibited the growth of M.
      aeruginosa in a concentration-dependent way. After a long time of exposure,
      stimulation effect disappeared gradually. Fv/Fm fluorescence parameters, YII and
      alpha changed from negative correlation to positive correlation or kept positive
      correlation with the extract of L. chinensis defoliation, which might affect the
      photosynthesis of M. aeruginosa at early time or help the cyanobacterium to
      survive in the stress environment by improving the efficiency of light energy.
      Ik, rETRmax and the content of algal chlorophyll-a changed from negative to
      significant negative correlation with the extract. Three-dimensional fluorescence
      spectra showed that the peak intensities of tryptophan and tyrosine fluorescence
      were only about one third in 2.0 g . L(-1) extract treatment when compared to the
      1.2 g . L(-1) extract treatment on day 15. At the same time, the peak intensity
      of humic acid fluorescence was weaker than that on day 1. Further study showed
      that the EC50 of algal growth was smaller than that of the traditional crops
      straw, which might achieve good effect to control the growth of algae with lower
      concentration of L. chinensis defoliation extract due to its strong allelopathy.

PMID- 26314112
TI  - [Toxicity of Coptis chinensis Rhizome Extracts to Green Algae].
AB  - Coptis chinensis contains antiseptic alkaloids and thus its rhizomes and
      preparations are widely used for the treatment of.fish diseases. In order to
      realize the risk of water ecosystems produced by this medical herb and
      preparations used in aquaculture, the present experiment was carried out to study
      the toxicity of Coptis chinensis rhizome extract (CRE) to Scenedesmus oblique and
      Chlorella pyrenoidosa grown in culture solution with 0.00 (CK), 0.088 (Tl), 0.44
      (T2) and 1.76 mg . L(-1) (T3) of CRE, respectively. The results show that low
      concentration of CRE (T1) inhibited the growth rate of the alga and high CRE (T2
      and T3) ceased growth and reproductions. CRE also decreased the chlorophyll and
      proteins in alga cells, indicating the inhibition of photosynthesis and protein
      biosynthesis, which could be direct reasons for the low growth rate and death of
      green alga. The efflux of protons and substances from alga cells led to pH
      reduction and conductivity increment in culture solution with CRE. Furthermore,
      the activity of superoxide dismutase in alga increased at the beginning of CRE in
      T1 and T2 treatments but decreased as time prolonged which was in contrast to
      high CRE treatment. And the long exposure to low CRE treatment behaved otherwise.
      This suggests that the low concentration of CRE could induce the resistant
      reactions in alga at initial time but high CRE concentration or long exposure
      even at low CRE concentration could inhibit the enzyme synthesis. Similarly,
      malondialdehyde in alga increased as CRE concentrations increased in culture
      solutions, implying the damage and high permeability of cell membrane. In
      general, Chlorella pyrenoidosa was more sensitive to CRE. The abuse of rhizomes
      and preparations in aquaculture and intensive cultivation of Coptis chinensis
      plants in a large scale might produce ecological risks to primary productivity of
      water ecosystems.

PMID- 26314113
TI  - [Formation Mechanism of the Disinfection By-product 1, 1-Dichloroacetone in
      Drinking Water].
AB  - A novel method using methyl tertiary butyl ether (MTBE) as extractant and 1,2
      dibromopropane as internal standard for the determination of the disinfection by
      producs 1,1-dichloroacetone (DCAce) by gas chromatography mass spectrometry (GC
      MS) was described. The formation process of DCAce and its influencing factors
      were discussed with L-leucine as the precursor during the chloramination process.
      The results indicated that the DCAce production increased with the increase of
      chloramine dosage when the chloramine addition was in the range of 5-30 mg . L(
      1). The DCAce amount produced under alkaline condition was higher than those
      produced under the neutral and acidic conditions, and the DCAce amount reduced
      with the increase of pH value. Temperature was another important factor that
      affected the DCAce formation from methylamine especially in the range of 15-35
      degrees C , and the higher the temperature, the more the DCAce produced. The
      formation process of DCAce from L-leucine by chloramine consisted of a series of
      complicated reactions, including substitution, oxidation, bond breaking, amino
      diazotization, reduction and so on, and eventually DCAce was formed.

PMID- 26314114
TI  - [Degradation Kinetics and Formation of Disinfection By-products During Linuron
      Chlorination in Drinking Water].
AB  - Chlorination degradation of linuron was studied using the common disinfectant
      sodium hypochlorite, the effects of chlorine dosage, pH value, bromine ion
      concentrationand temperature were systematically investigated, and the formation
      characteristics of disinfection by-products (DBPs) during the chlorination
      reaction was analyzed. The results showed that the chlorination degradation
      kinetics of linuron by sodium hypochlorite could be well described by the second
      order kinetic model. Moreover, pH values had a great impact on the degradation
      reaction, and the rate constant reached the maximum level at pH 7, and the base
      elementary reaction rate constants of HOCl and OCl- with linuron were 4.84 x
      10(2) L . (mol . h)(-1) and 3.80 x 10(2) L . (mol . h)(-1), respectively. The
      reaction rate decreased with the addition of bromide ion and increased with
      increasing temperature. Furthermore, many kinds of disinfection by- products were
      produced during the chlorination degradation of linuron, including CF, DCAN, TCNM
      and halogen acetone. Under conditions of different solution pH and different
      bromide ion concentrations, there would be significant difference in the types
      and concentrations of disinfection by-products.

PMID- 26314115
TI  - [Interference for Various Quench Agents of Chemical Disinfectants on Detection of
      Endotoxin Activities in Water].
AB  - The quenching agents such as histidine, glycine, ascorbic acid, Tween-80, sodium
      sulfite and sodium hyposulfite are commonly used for quenching the residual
      disinfectant in water. In this paper, in order to select the optimal type and
      concentration range of quenching agents prior to the Limulus assays, the
      interference effects of each quenching agent at different concentrations on
      endotoxin detection were investigated by the Limulus assays of kinetic-turbidity.
      Our results identified that, as for 0-1.0% concentration of histidine, ascorbic
      acid, Tween-80, sodium sulfite (pH unadjusted and pH neutral), interference on
      the Limulus assays was existed. Hence, these quenching agents could not be
      applied as neutralizers prior to Limulus assays. Although, there was no
      interference on endotoxin detection for the glycine, a yellow color, developed by
      the quenching products of glycine and glutaric dialdehyde, contributed to false
      positive results. Hence, glycine should not be used as quenching agents in
      Limulus assays for samples containing glutaric dialdehyde. Compared with other
      quenching agents as histidine, glycine, ascorbic acid, Tween-80, sodium sulfite,
      0-1.0% concentration of sodium hyposulfite elicited no obvious interference,
      while 1.0%-5.0% concentration of sodium hyposulfite illustrated exhibition effect
      for endotoxin detection. All in all, compared with other quenching agents as
      histidine, glycine, ascorbic acid, Tween-80 and sodium sulfite, sodium
      hyposulfite is suitable for quenching chemicals prior to endotoxin detection and
      less than 0.5% of concentration is allowable.

PMID- 26314116
TI  - [Ammonium Adsorption Characteristics in Aqueous Solution by Dairy Manure
      Biochar].
AB  - The adsorption characteristics of ammonium from aqueous solution onto biochar
      derived from dairy manure were investigated as a function of parameters such as
      solution pH, particle size, adsorbent dosage, temperature and competitive
      cations. The results indicated that the effects of other cations on the
      adsorption of ammonium followed the order of preference Na > Ca2+ at identical
      mass concentrations. It was observed that pH played an important role in the
      ammonium adsorption and the optimal pH values ranged between 5 and 8. The kinetic
      data fitted the pseudo-second-order model (R2 = 0.967 3) but showed very poor
      fits for the pseudo-first-order model (R2 = 0.765 9) and the Elovich model (R2 =
      0.724 9). The results from the Intra-particle model also showed that there were
      two separate stages in sorption process, which were external diffusion and the
      diffusion of inter-particle. Adsorption isotherms for dairy manure biochar were
      fitted the Freundlich model (R2 = 0.976 2) more effectively than other models.
      Thermodynamics parameters such as free energy (DeltaGtheta), enthalpy
      (DeltaHtheta), and entropy (DeltaStheta) were also determined, which indicated
      that the adsorption was a spontaneous and endothermic process.

PMID- 26314117
TI  - [Absorption of Uranium with Tea Oil Tree Sawdust Modified by Succinic Acid].
AB  - In order to explore how the modification of succinic acid improves the adsorption
      of tea oil tree sawdust for uranium, the tea oil tree sawdust was modified by
      succinic acid, after the pretreatments of crushing, screening, alkalization and
      acidification. Infrared analysis indicated carboxylic acid groups and ester
      groups were added to the sawdust after modification, and scanning electron
      microscope demonstrated after modification the appearance of tea oil tree sawdust
      was transferred from the structure like compact and straight stripped into the
      structure like loose and wrinkled leaves, which meant modification increased its
      inner pores. By the static experiments, effects of reaction time between
      adsorbent and solvent, dosage of adsorbent, temperature, pH value and initial
      concentration of uranium were investigated. The results showed that after the
      modification by succinic acid, the absorption rate of tea oil tree sawdust for
      uranium increased significantly by about 20% in 12.5 mg . L(-1) initial
      concentration uranium solution. Adsorption equilibrium was achieved within 180
      min, and the kinetic data can be well described by the pseudo-second-order
      kinetic model. The experimental adsorption isotherm followed the Langmuir and
      Freundlich models. In addition, the maximum adsorption amounts of tea oil tree
      sawdust after modification calculated from Langmuir equation raised from 21.413 3
      to 31.545 7 mg . g(-1) at 35 degrees C and pH 4.0.

PMID- 26314118
TI  - [Effect of Membrane Wettability on Membrane Fouling and Chemical Durability of
      SPG Membranes].
AB  - Shirasu porous glass (SPG) membranes have been applied for microbubble aeration
      in aerobic wastewater treatment. In the present study, both hydrophilic and
      hydrophobic SPG membranes were used in a microbubble-aerated biofilm reactor with
      online chemical cleaning, and their membrane fouling and chemical durability were
      determined to be strongly dependent on the membrane wettability. The fouling
      layer formed on the surface of both membranes was confirmed to be mainly organic
      fouling, and the hydrophobic membrane showed a relatively stronger resistance to
      the organic fouling. The severe chemical corrosion of the hydrophilic membrane
      was observed due to exposure to the alkaline sodium hypochlorite solution used
      for chemical cleaning, which resulted in significant increases in the median pore
      diameter and the porosity. On the other hand, the pore structure of the
      hydrophobic membrane changed slightly when exposed to the alkaline sodium
      hypochlorite solution, suggesting its strong alkali-resistance due to the non
      wetting surface. However, the surface hydrophobic groups of hydrophobic membrane
      could be oxidized by sodium hypochlorite solution, resulting in more wettable
      membrane surface. The hydrophobic membrane also showed better performance in the
      respects of oxygen transfer, contaminant removal and energy-saving. Therefore,
      the hydrophobic membrane seemed more appropriate to be applied for microbubble
      aeration in aerobic wastewater treatment process.

PMID- 26314119
TI  - [TiO2-Induced Photodegradation of Levofloxacin by Visible Light and Its
      Mechanism].
AB  - Levofloxacin is an emerging pollutant. Single levofloxacin and TiO2 have no
      visible-light activity. However, photodegradation of levofloxacin dramatically
      enhanced in the presence of TiO2 under visible light irradiation. Considering
      this finding, he photodegradation of levofloxacin over TiO2 was investigated
      under visible light irradiation. Effects of TiO2 dosage, levofloxacin
      concentration, and solution pH on levofloxacin photodegradation were examined by
      monitoring its concentration decay with time. The results showed that
      levofloxacin photodegradation fitted the Langmuir-Hinshelwood kinetic model.
      Solution pH, TiO2 dose, and levofloxacin concentration had significant effects on
      the photodegradation rates. In addition, batch adsorption experiments revealed
      that adsorption of levofloxacin on TiO2 conformed to the pseudo-second-order
      kinetics and the Langmuir isotherm. DRS spectrum of levofloxacin-adsorbed TiO2
      suggested that a surface complex was formed between levofloxacin and TiO2.
      Addition of radical scavengers and N2-degassing affecting levofloxacin
      photodegradation indicated that the superoxide ion radical was mainly active
      species. UV-Vis spectra of a deaerated TiO2 and levofloxacin suspensions further
      confirmed that the electron injection into TiO2 conduction band took place under
      visible light irradiation. Based on these results, a charge-transfer mechanism
      initiated by photoexcitation of TiO2/ levofloxacin surface complex was proposed
      for levofloxacin photocatalytic degradation over TiO2 under visible light. This
      study indicates that the charge-transfer-complex-mediated photocatalytic
      technique has promising applications in the removal of colorless organic
      pollutants.

PMID- 26314120
TI  - [Performance of Novel Macromolecule Flocculant in the Treatment of Wastewater
      Containing Cr (VI) Ions].
AB  - A novel macromolecule flocculant, polyethyleneimine-sodium xanthogenate (PEX),
      was applied in the treatment of wastewater containing Cr(VI) ions. The trapping
      performance of PEX for Cr(VI) ions was studied, and effects of selective
      important factors, such as initial Cr(VI) concentration, pH value, coexisting
      inorganic substance and turbidity etc., on the removal of chromium by PEX were
      investigated. The experimental results indicated that PEX could efficiently
      remove different concentrations of chromium in strong acidic media. The maximum
      removal rate of Cr(VI) and total Cr reached 99.1% and 96.6% at pH 2.0,
      respectively. The existence of influencing substance (e. g. NaCl, NaF, Na2SO4,
      CaCl2 and turbidity) would inhibit the removal of Cr(VI) ions, and promote the
      removal of total Cr to some extent. Fourier transform infrared spectroscopy
      (FTIR) analysis showed that the behaviors in the removal of Cr(VI) ions included
      reduction and chelation. Cr(VI) ions were reduced to Cr(III) ions by
      dithiocarboxylic acid groups on the PEX molecule, and then chelating reactions
      existed between Cr(III) ions and dithiocarboxylic acid groups and amino groups of
      PEX.

PMID- 26314121
TI  - [On-line Estimation for the Amount of Stored PHA in Activated Sludge Based on OUR
      HPR Measurements].
AB  - Activated sludge process is an important approach for industrial
      Polyhydroxyalkanoate ( PHA ) production. Off-line measurement with a time lag and
      complex analysis, is a common method for PHA, but is not suitable for the process
      control of PHA production. Based on a model for simultaneous storage and growth
      soluble microbial products (SSAG-SMP), it is assumed that there is the linear
      relationship between the PHA synthesized and OUR or HPR, respectively. Further, a
      novel method to estimate PHA content based on in-situ monitoring data of oxygen
      uptake rate (OUR) and hydrogen-ion production rate (HPR) is established in this
      paper. The results of modeling OUR and HPR under different substrate
      concentrations showed that oxygen consumption proportion (kPHA,OUR) and proton
      consumption proportion (kPHA,HPR) of PHA synthesis were 0.67 and 0.57,
      respectively. The predicted results based on the linear relationship were
      essentially consistent with measured ones, and indicated that the method is
      feasible

PMID- 26314122
TI  - [Formation Mechanism of Self-forming Dynamic Membrane During Separation of High
      concentration Sewage Sludge Fermented for Acid Production].
AB  - Self-forming dynamic membrane was used to separate high-concentration sludge
      fermentation liquid, and the formation mechanism and separation efficiency of
      dynamic membrane were investigated. The results indicated that the impact of
      sludge concentrations was negligible on the formation of dynamic membrane. Though
      membrane flux could be influenced by sludge concentration at the initial stage of
      membrane formation process, the influence was not obvious at the stable stage.
      Membrane flux was improved with increasing filter cloth pore size and stirring
      speeds. Moreover, the results indicated that the formation process of dynamic
      membrane followed the dead-end filtration model, which could be divided into four
      stages. Firstly, filter cloth pore was blocked by those sludge particles with the
      diameter similar to the pore size of filter cloth. Secondly, sludge particles
      formed monolayer sludge on the filter cloth. Thirdly, sludge particles formed
      multilayer sludge on the filter cloth. Finally, large sludge particles deposited
      onto the sludge layer. After formation of the dynamic membrane, the retention
      efficiency of sludge particles and SCOD could reach 98% and 28% , respectively,
      and the permeation efficiency of VFAs was over 82%. Proteins in EPS were the main
      component of the dynamic membrane.

PMID- 26314123
TI  - [Influence of Air Flux on Municipal Sludge Biodrying in a Pilot Scale Test].
AB  - A drum-type biodrying pilot scale test system was made to treat the municipal
      sludge. Sludge was mixed with barks according to certain proportion, and was used
      to study the influence of air flux on municipal sludge biodrying through
      parameter detection, such as temperature, moisture content, pH and volatile solid
      (VS). Results showed that air flux had a great influence on the effect of
      biodrying. When the air flux was 120 L . (h . kg)(-1), the best result was
      obtained, the highest sludge temperature was 66 degrees C and the temperature
      could remain upon 55 degrees C for more than 40 h. After 111 h, the moisture
      content reduced to 56% . The pH remained at 6.5-8.5 through the whole biodrying
      process. As a result, the microorganism activities would not be affected. The
      sludge inside the drum-type biodrying system was homogeneous. This research
      provides a reference about sludge treatment using a continues flow process by
      drum-type biodrying system.

PMID- 26314124
TI  - [Extraction of Heavy Metals from Sludge Using Biodegradable Chelating Agent N,N
      bis(carboxymethyl) Glutamic Acid Tetrasodium].
AB  - N, N-bis (carboxymethyl) glutamic acid tetrasodium (GLDA), a novel biodegradable
      and green chelating agent, has excellent metal chelating ability. Batch
      experiment was conducted to study the extraction process of Cd, Ni, Cu and Zn in
      industrial sludge using GLDA. The effects of contact time, pH of the system,
      content of chelating agent were investigated, and the forms of heavy metals in
      sludge pre- and post-extraction using the modified BCR sequential extraction
      procedure were studied. The results showed that GLDA was effective for cadmium
      extraction in sludge. Several heavy metals could be effectively extracted under
      the condition of pH 4 and molar ratio of chelating agent to total heavy metal
      3:1. Residual fraction took the largest fraction in Zn, which caused the low
      extraction efficiency of this metal. Chelating properties were related not only
      to contact time, pH, chelating agent's concentration, and stability constant but
      also to species distribution of metals.

PMID- 26314125
TI  - [Biodiversity and Function Analyses of BIOLAK Activated Sludge Metagenome].
AB  - The BIOLAK is a multi-stage activated sludge process, which has been successfully
      promoted worldwide. However, the biological community and function of the BIOLAK
      activated sludge ( the core component in the process) have not been reported so
      far. In this study, taking Lianyungang Dapu Industrial Zone WWTP as an example, a
      large-scale metagenomic data (428 588 high-quality DNA sequences) of the BIOLAK
      activated sludge were obtained by means of a new generation of high-throughput
      sequencing technology. Amazing biodiversity was revealed in the BIOLAK activated
      sludge, which included 47 phyla, 872 genera and 1351 species. There were 33 phyla
      identified in the Bacteria domain (289 933 sequences). Proteohacteria was the
      most abundant phylum (62.54%), followed by Bacteroidetes (11.29%), Nitrospirae (
      5. 65%) and Planctomycetes (4.79%), suggesting that these groups played a key
      role in the BIOLAK wastewater treatment system. Among the 748 bacterial genera,
      Nitrospira (5.60%) was the most prevalent genus, which was a key group in the
      nitrogen cycle. Followed by Gemmatimonas (2.45%), which was an important genus in
      the biological phosphorus removal process. In Archaea domain (1019 sequences),
      three phyla and 39 genera were detected. In Eukaryota domain (1055 sequences), 60
      genera and 10 phyla were identified, among which Ciliophora was the largest
      phylum (257 sequences). Meanwhile, 448 viral sequences were detected in the
      BIOLAK sludge metagenome, which were dominated by bacteriophages. The proportions
      of nitrogen, aromatic compounds and phosphorus metabolism in the BIOLAK sludge
      were 2.50%, 2.28% and 1.56%, respectively, which were higher than those in the
      sludge of United States and Australia. Among four processes of nitrogen
      metabolism, denitrification-related genes were most abundant (80.81%), followed
      by ammonification (12.78%), nitrification,(4.38%) and nitrogen fixation (2.04%).
      In conclusion, the BIOLAK activated sludge had amazing biodiversity, meanwhile,
      functional genes involved in nitrogen, aromatic compounds and phosphorus
      metabolism were very abundant.

PMID- 26314126
TI  - [Characteristics of Nitrogen Removal by a Heterotrophic Nitrification-Aerobic
      Denitrification Bacterium YL].
AB  - Traditional process of autotrophic nitrification-anaerobic denitrification
      usually has problems of long procedure and low efficiency. To overcome these
      problems, a heterotrophic nitrification-aerobic denitrification bacterium YL was
      isolated from a domesticated mature SBR reactor with efficient simultaneous
      nitrification and denitrification ability, and was identified as Pseudomonas
      aeruginosa YL. Meanwhile, the characteristics of the nitrogen removal of strain
      YL was investigated through single-factor experiments and an orthogonal
      experiment. The results showed that the preferred conditions were: succinate as
      the carbon source, C/N ratio of 10, pH of 7.0, temperature of 30 degrees C, and
      the shaking speed of 160-200 r . min(-1), while the removal rate of ammonia
      oxidation was 5. 05 mg . (g . h)(-1), the transformation rate of TOC was 45.95 mg
      . (g . h)(-1), and the removal rates of nitrogen and TOC were 100% and 90.8%,
      respectively. Nitrite, nitrate and hydroxylamine could also be metabolized by
      strain YL, and the removal rates were 92.7%, 93.6% and 94.8%, respectively. The
      most important influencing factor on aerobic denitrification of strain YL was C/N
      ratio. Under the optimal conditions (C/N = 10, T = 30 degrees C , r = 200 r .
      min(-1), pH = 7), the removal rates of nitrate and total nitrogen were 94.6% and
      76.3%, respectively. Hence, strain YL could remove nitrogen by heterotrophic
      nitrification-aerobic denitrification independently, quickly, and effectively.

PMID- 26314127
TI  - [Biodegradation Characteristics and Kinetics of p-nitrophenol by Strain
      Arthrobacter sp. CN2].
AB  - To investigate the application potential of the p-nitrophenol-degrading bacterium
      Arthrobacter sp. CN2 in practice, the effects of pH, salinity and additional
      carbon source were determined, and the degradation kinetics of p-nitrophenol was
      analyzed. Strain CN2 could degrade p-nitrophenol efficiently in a wide range of
      pH (7.0-8.0) and elevated salinity (0-60 g . L(-1)). Investigation of additional
      glucose found that 0.5% of glucose could significantly increase the degrading
      speed and the time to reach 90% of degradation rate was shortened by 16 hours.
      These results indicated that strain CN2 could degrade p-nitrophenol efficiently
      under different conditions and had a great potential for application in practice.

PMID- 26314128
TI  - [Biodegradation of Pyrene by Intact Cells and Spores of Brevibacillus brevis].
AB  - Biodegradation characteristics of pyrene by intact cells and spores of
      Brevibacillus brevis were investigated. The results revealed that the degradation
      efficiency of 1 mg . L(-1) pyrene by B. brevis intact cells reached 53% within 5
      d. Four hydroxy metabolites were detected by LC-MS/MS during the degradation of
      pyrene by intact cells and intracellular enzymes, including 1-hydroxy-pyrene, 9-
      phenanthrol, alpha-naphthol and beta-naphthol. The amount of products first
      increased and then declined in the degradation system with intact cells, while
      the macromolecular metabolites showed a continuous accumulation tendency in the
      degradation system with intracellular enzymes, proving that some degrading
      enzymes of B. brevis could be induced by the products generated during the
      degradation, and then the enzymes induced could further degrade these degradation
      products. The amount of cells germinated from spores in MSM containing pyrene was
      1.5 x 10(9) cells . L(-1), and the degradation rate of pyrene (1 mg . L(-1))
      within 5 d reached 15%.

PMID- 26314129
TI  - [Investigation of Antibiotic Resistance Genes (ARGs) in Landfill].
AB  - Antibiotic resistant genes (ARGs), an emerging contaminant, have been detected
      worldwide in various environments such as sediments and river. However, little is
      known about ARGs distribution in landfill. In this study, we investigated five
      ARGs [sulfonamides resistant genes (sulI and sulII), chloramphenicols resistant
      gene (cat), beta-lactams resistant gene (bla-SHV), and tetracyclines resistant
      gene (tetW)] in refuse samples collected from jiangeungou landfill (Xi'an, China)
      by real-time PCR. We then correlated the ARGs and physiochemical properties of
      refuse to examine the link between them. Results showed that all tested ARGs have
      been detected in all samples, suggesting that landfill served as ARGs reservoir.
      The highest copies numbers of sulII, sulI, tetW, bla-SHV, and cat were (3.70 +/-
      0.06) x 10(8) copies . g(-1) ( dry refuse), (9.33 . 0.06) x 10(6) copies . g(-1)
      (dry refuse), (2.27 0.08) x 10(5) copies . g(-1) (dry refuse), (3.68 +/- 0.09) x
      10(4) copies . g(-1) (dry refuse), and (1.39 +/- 0.10) x 10(4) copies . g(-1)
      (dry refuse), respectively. Further, sulI, sulII, and cat positively correlated
      to moisture and sulI and cat negatively correlated to pH.

PMID- 26314130
TI  - [Investigation of Antibiotic Resistance of Indigenous Bacteria and Abundance of
      Class I Integron in Matrix of Constructed Wetlands of Different Configurations].
AB  - Environmental indigenous bacteria (Staphylococcus and Pseudomonas) were isolated
      from 9 different constructed wetlands (CWs) in summer and winter. The antibiotic
      resistance analysis of the isolated bacteria was conducted by Kirby-Bauer disc
      agar diffusion method. And the quantitative PCR assay was used to quantify the
      abundance of class I integron (int1) in the matrix of CWs. The results indicated
      that over 84% of isolates among the 522 Staphylococcus strains and 543
      Pseudomonas strains had antibiotic resistance and above 68% of isolates had multi
      antibiotic resistance, the average of MRI index was 0.22. Antibiotic resistance
      of indigenous bacteria in CWs was at the same resistance level of human or animal
      bacteria in certain environment, indicating that indigenous bacteria from
      constructed wetlands had relatively high level of resistance. Staphylococcus and
      Pseudomonas strains had higher resistances to Ampicillin (AMP) and
      Sulfamethoxazole (SXT), and extremely low resistance rates of lower than 3% to
      Tetracycline (TE), Gentamicin (CN) and Ciprofloxacin (CIP). To Ceftazidime (CAZ)
      and Chloramphenicol (C), the two kinds of indigenous bacteria showed distinctly
      different resistances. Quantitative PCR revealed that the abundance of intl in
      CWs was 1.14 x 10(5)-5.66 x 10(5) copies . g(-1), and its relative abundance was
      0.54%-3.68%. Both of season and wetland type had important impact on antibiotic
      resistance and abundance of int1. The antibiotic resistance rate and the multiple
      resistance index (MRI) for the indigenous bacteria and the abundance of int1 in
      summer were higher than those in winter. Among three types of CWs, the antibiotic
      resistance rate and the MRI value were the highest in the downward vertical flow,
      while the int1 abundance was the highest in the sub-surface flow. The research
      indicated that indigenous bacteria acquired antibiotic resistance due to long
      term exposure to antibiotics of certain concentrations and antibiotic-resistant
      intestinal bacteria in sewage environment. The environmental risks of antibiotic
      resistant bacteria and resistant genes in CWs should not be ignored.

PMID- 26314131
TI  - [Effects of Nitrate and CH4 on Anaerobic Oxidation of BETX in Landfill Cover
      Soils].
AB  - BETX is one of the important components of stink organic gases in landfills,
      which simultaneously release much of greenhouse CH4. The microorganisms in
      landfill cover soils are able to degrade CH4 and BETX. Therefore, improving the
      capacity of biological oxidation of microorganisms in landfill cover soils can
      effectively reduce and control pollution caused by landfill gases. Some electron
      acceptors can couple to anaerobic oxidation of methane and some organic
      pollutants, thus eliminating methane and organic substances. Based on the above
      theory, this research investigated the effect of nitrate (NO3-) and CH4 on
      anaerobic degradation of benzene series (toluene, xylene and isopropyl benzene)
      with coexistence of SO4(2-) in landfill cover soils through static incubation
      experiment. The results showed that BTEX inhibited the degradation of CH4 without
      adding nitrate, however, BTEX instead improved the removal of CH4 after nitrate
      addition. Although single addition of nitrate or CH4 could improve the removal of
      BTEX in landfill cover soils, adding both of them could improve the removal of
      BTEX better as the removal efficiencies for benzene, toluene and isopropyl
      benzene were respectively reached 65%, 88% and 82%, much higher than those of
      53%, 76% and 31% when not adding nitrate and CH4. The process of anaerobic
      methane oxidation coupled to nitrate reduction was able to synchronously improve
      anaerobic oxidation of BETX.

PMID- 26314132
TI  - [Spatial Heterogeneity of Soil Respiration in a Planted Larch Forest in Shanxi
      Plateau].
AB  - Based on the data from a planted larch forest in Panquangou Natural Reserve of
      Shanxi Province, at three sampling scales (4, 2, and 1 m, respectively), soil
      respiration (Rs) and its affecting factors including soil temperature at 5 cm
      (T5), 10 cm (T10), and 15 cm (T15) depths, soil water content (Ws), litter mass
      (Lw), litter moisture (Lm), soil total carbon (C), and soil total nitrogen ( N)
      were determined. The spatial heterogeneities of Rs and the environmental factors
      were further analyzed and their intrinsic correlations were established. The
      results of traditional statistics showed that the spatial variations of Rs and
      the all measured factors were in the middle range; Rs were highly significantly
      positively correlated with T10, T15, and N (P < 0.01); significantly positively
      correlated with Lm (P < 0.05); highly significantly negatively correlated with
      C/N ratio (P < 0.01); and not significantly correlated with T5, Ws, Lw and C (P >
      0.05). Multiple stepwise regression analysis indicated that the four factors of
      Lm, T10, N, and Ws together accounted for 36% of Rs heterogeneity. The results of
      geo-statistical analysis demonstrated that Rs was in a medium spatial
      autocorrelation; random and structural factors accounted for 39.5% and 60.5% of
      Rs heterogeneity, respectively. And the factors such as climate, landform, and
      soil played a leading role. The results also illustrated that the ranges for soil
      factors were different and the range for both Rs and T10 was 25 meters. The
      fractal dimension of the soil index was in the following order: Lw and C/N ratio
      (1.95) > N (1.91) > C (1.89) > Rs (1.78) > Lm (1.77 ) > Ws (1.69) > T10 (1.42).
      The spatial distribution of Rs was in consistent agreement with those of T10, Lm,
      C, and N; but different with those of Ws and C/N ratio. With a fixed cofidence
      level and certain estimated accuracy, the required sampling number of each item
      differed, corresponding to its spatial variation degree.

PMID- 26314133
TI  - [Effects of Nitrogen Fertilization on Soil Respiration and Temperature
      Sensitivity in Spring Maize Field in Semi-Arid Regions on Loess Plateau].
AB  - Understanding the effects of nitrogen fertilization on soil respiration rate and
      its temperature sensitivity (Q10) is of critical importance to predict the
      variability of soil respiration in cropland. A field experiment was established
      in a rain-fed spring maize cropland (Zea mays L. ) in the State Key Agro
      Ecological Experimental Station in the Loess Plateau in Changwu County, Shaanxi
      Province, China. The experiment comprised of two treatments: no N-fertilizer
      application ( CK) and N-fertilizer application with 160 kg N . hm(-2) (N). Soil
      respiration rate, soil temperature, soil moisture, yields, aboveground biomass
      and root biomass were measured in two continuous spring maize growing seasons
      from April 2013 to September 2014. The cumulative soil CO2 emissions were
      increased by 35% in 2013 and 54% in 2014 in N treatment as compared to CK
      treatment. Though nitrogen fertilization significantly increased the cumulative
      soil CO2 emissions (P < 0.05), it did decrease evidently the temperature
      sensitivity of soil respiration (P < 0.05) . The Q10 values in N treatment were
      decreased by 27% and 17% compared with CK treatment in 2013 and 2014,
      respectively. Nitrogen fertilization significantly increased the maize yields,
      aboveground biomass and root biomass (P < 0.05). Root biomasses in N treatment
      were 32% and 123% greater than those in CK treatment of 2013 and 2014,
      respectively. Nitrogen fertilization had no marked influence on soil temperature
      or moisture. Root biomass was a critical biotical factor for variation of soil
      respiration under nitrogen fertilization.

PMID- 26314134
TI  - [Distribution Characteristics of Heavy Metals in the Street Dusts in Xuanwei and
      Their Health Risk Assessment].
AB  - Relationship between high lung cancer incidence in Xuanwei residents and
      environmental pollution has been a hot topic in the field of environmental
      sciences. Street dusts in Xuanwei power plant area as well as its upwind area
      (Banqiao town) and downwind area (Laibin town, Tangtang town) were collected.
      Chemical elements in the street dust samples were investigated using ICP-MS.
      Health risk assessment of heavy metals in the street dusts was carried out using
      the US EPA Health Risk Assessment Model. Our results showed that the mass level
      of Al, V, Ni, Co, Zn and Cd in street dusts followed the order of Xuanwei power
      plant > Laibin town > Tangtang town. The mean concentrations of V, Cd, Cr, Cu,
      Mn, Co, Ni, Pb, As and Zn were all higher than the background values in Yunnan
      soil, indicating that the street dusts of Xuanwei city have been heavily polluted
      by those metals. The health risk assessment results showed that the non-cancer
      hazard risks induced by the 10 heavy metals were higher to children compared to
      adults. The heavy metals in street dust were mainly ingested by human bodies
      through hand-mouth ingestion. The 5 carcinogenic metals, including Cd, Cr, Ni, Cr
      and As, had a potential risk of carcinogenicity in human after exposed to the
      dusts. Cr was the major toxic element to the local children's health.

PMID- 26314135
TI  - [Spatial Distribution of Magnetic Properties of Street Dust in Baoji City and Its
      Implications of Environment].
AB  - Magnetic characteristics of street dust can reflect important information of
      environmental conditions. Environmental magnetic measurements were carried out on
      the samples of street dust in Baoji City. The results indicated a high
      concentration of magnetic minerals in street dust, dominated by multiple domain
      (MD) and pseudo-single domain (PSD) ferrimagnetic minerals which were mainly from
      the traffic and industrial pollution. According to the Spatial Distribution of
      Magnetic Properties of Street Dust, Baoji City was divided into six districts (A,
      B, C, D, E and F areas). In the A (Chuangxin road and Gaoxin road eight) and B
      (Dongfeng road and Maying road) areas, chilf, SIRM and soft values were the
      highest in the six areas and much higher than the average values and background
      values, indicating heavy pollution. The pollution sources were industry and
      vehicles. chilf, SIRM and soft values were relatively high in the C ( Huoju road
      and Yikang road) area, indicating moderate pollution. The pollution source was
      vehicles. However, the magnetic parameters were lower than the average values and
      background values in D (Jinger road and Renmin road), E (Qingjiang road and
      Jiangtan road) and F (Chencang road) area, suggesting mild pollution. The
      pollution was caused by vehicle emission.

PMID- 26314136
TI  - [Effect of Long-term Fertilizer Application on the Stability of Organic Carbon in
      Particle Size Fractions of a Paddy Soil in Zhejiang Province, China].
AB  - Effects of chemical fertilizers and organic manure on the soil organic carbon
      (SOC) content in particle size fractions of paddy soil were investigated in a 17
      year long-term fertilization field experiment in Zhejiang Province, China. The
      inherent chemical composition of silt- and clay-associated SOC was evaluated with
      solid-state 13C-NMR spectroscopy. Compared to CK (no fertilizer treatment), NPKRS
      (NPK fertilizers plus rice straw) , NPKOM (NPK fertilizers plus organic manure) ,
      NPK (NPK fertilizers) and OM (organic manure alone) treatments significantly (P
      <0. 05) increased the SOC content of sand- (2-0.02 mm), silt- (0.02-0.002 mm) and
      clay-sized (< 0.002 mm) fractions. However, no significant difference was
      observed in the accumulation of silt- and clay-associated SOC between CK and rice
      straw (RS) treatments. Besides, in comparison with plots applied with NPK
      fertilizers alone, combined application of organic amendments and NPK fertilizers
      facilitated the storage of newly sequestered SOC in silt- and clay-sized
      fractions, which could be more conducive to the stability of SOC. Based on 13C
      NMR spectra, both silt and clay fractions were composed of Alkyl-C, O-alkyl-C,
      Aromatic-C and carbonyl-C. Changes in the relative proportion of different C
      species were observed between silt and clay fractions: the clay fraction had
      relatively more Alkyl-C, carbonyl-C and less O-alkyl-C, Aromatic-C than those in
      the silt fraction. This might be ascribed to the fact that the organic matter
      complexed with clay was dominated by microbial products, whereas the silt
      appeared to be rich in aromatic residues derived from plants. The spectra also
      showed that the relative proportion of different C species was modified by
      fertilization practices. In comparison with organic amendments alone, the
      relative proportion of Alkyl-C was decreased by 9.1%-11.9% and 13.7%-19.9% under
      combined application of organic amendments and chemical fertilizers, for silt and
      clay, respectively, and that of O-alkyl-C was increased by 2.9%-6.3% and 13.4%
      22.1%, respectively. These results indicated that NPKOM and NPKRS treatments
      reduced the decomposition rate of SOC. The aromaticity, hydrophobicity and,
      hence, chemical recalcitrance of silt- and clay-associated SOC in the NPK
      fertilizer treatments were lower than those of the organically amended plots and
      unfertilized treatments, indicating decreased recalcitrance of SOC against
      decomposition. We concluded that long-term application of organic manure combined
      with chemical fertilizers, either through increased accumulation of both
      recalcitrant compounds and carbohydrates or reduced decomposition of organic
      matter, was a sustainable strategy for facilitating carbon accumulation of the
      paddy soil investigated in this study.

PMID- 26314137
TI  - [Effects of Different Reclaimed Scenarios on Soil Microbe and Enzyme Activities
      in Mining Areas].
AB  - Abstract: Ecological degradation in the mining areas is greatly aggravated in
      recent several decades, and ecological restoration has become the primary measure
      for the sustainable development. Soil microbe and enzyme activity are sensitive
      indices to evaluate soil quality. Ecological reconstruction was initiated in
      Antaibao mining area, and we tested soil physicochemical properties, microbial
      populations of azotobacteria, nitrifying-bacteria and denitrifying-bacteria, and
      enzyme activities (including sucrose, polyphenol oxidase, dehydrogenase and
      urease) under different regeneration scenarios. Regeneration scenarios had
      significant effects on soil physicochemical properties, microbial population and
      enzyme activities. Total nitrogen was strongly correlated with azotobacteria and
      nitrifying-bacteria, however, total nitrogen was not correlated with denitrifying
      bacteria. Phenol oxidase activity was negatively correlated with soil organic
      carbon and total nitrogen, but other enzyme activities were positively correlated
      with soil organic carbon and total nitrogen. Principal Component Analysis ( PCA)
      was applied to analyze the integrated fertility index (IFI). The highest and
      lowest IFIs were in Robinia pseudoacacia-Pinus tabuliformis mixed forests and un
      reclaimed area, respectively. R. pseudoacacia-P. tabuliformis mixed forests were
      feasible for reclaimed mining areas in semi-arid region Northwest Shanxi.

PMID- 26314138
TI  - [Soil Microorganism Characteristics and Soil Nutrients of Different Wetlands in
      Sanjinag Plain, Northeast China].
AB  - Four typical wetland types (i.e. wetlands with the following dominant plant
      species: Calamagrostis angustifolia + Salix brachypoda, Calamagrostis
      angustifolia, Carex lasiocarpa and Phragmites australis) of the Honghe reserve in
      Sanjiang Plain were studied to investigate the distribution of soil microorganism
      quantity and enzyme activity and their relationships with soil nutrients. The
      results showed that in 0-30 cm soil layer of these four wetlands: (1) Contents of
      soil total organic carbon, total nitrogen and total phosphorus decreased with the
      increase of soil depth, while available nitrogen, phosphorus and potassium did
      not exhibit regularly changes. Moreover, there were significantly different for
      soil nutrient contents among different wetland types (P < 0.05). (2) The number
      of soil microorganism was bacteria > actinomycetes > fungi, furthermore, the
      number of three microbial colonies all decreased with the increase of soil depth.
      Total soil microbial number of C. angustifolia wetland was the highest and that
      of C. lasiocarpa wetland was the lowest. (3) Soil invertase and cellulase
      activities decreased with soil depth, while soil catalase activity showed no
      consistent changes. Three kinds of enzyme activities in C. angustifolia + S.
      brachypoda and C. angustifolia wetlands were significantly higher than those of
      C. lasiocarpa and P. australis wetlands (P < 0.05). (4) The correlation analysis
      showed that soil bacteria, fungi and cellulose activity had a significant
      correlation with indicators of soil nutrients. But there was no correlation
      between actinomyces, invertase and available potassium, as well as between
      catalase and available potassium, available phosphorus. Overall, soil
      microorganism and enzyme activities are important indicators for reflecting the
      status of soil nutrients.

PMID- 26314139
TI  - [Strengthening Effects of Sodium Salts on Washing Kerosene Contaminated Soil with
      Surfactants].
AB  - The impact of sodium salt on kerosene contaminated soil washing with surfactants
      was investigated. The results indicated that sodium silicate greatly enhanced the
      washing efficiency of SDS. Sodium tartrate can largely enhance the washing
      efficiency of SDBS and Brij35. Sodium salts can enhance the washing efficiency on
      kerosene contaminated with TX-100. No significant differences were observed
      between different sodium salts. Sodium salt of humic acid and sodium silicate had
      similar enhancement on kerosene contaminated soil washing with saponin. Sodium
      humate can be a better choice since its application can also improve soil
      quality. The enhancement of sodium silicate on kerosene contaminated soil washing
      with Tw-80 increased with the increase of Tw-80 dosage. However, the impact of
      sodium chloride and sodium tartrate was opposite to sodium silicate. Sodium salts
      can reduce surface tension and critical micelle concentration of ionic
      surfactants to enhance the washing. Sodium salts can also reduce re-adsorption of
      oil to soil with nonionic surfactants to enhance the washing. Kerosene
      contamination can increase the contact angle of soil, which indicated the
      increase of hydrophilicity of soil. Washing with surfactants can reduce the
      hydrophilicitiy of soil according to contact angle measurement, which indicated
      that kerosene contaminated soil remediation with surfactant can also benefit
      nutrient and water transportation in the contaminated soil.

PMID- 26314140
TI  - [Effects and Biological Response on Bioremediation of Petroleum Contaminated
      Soil].
AB  - Bioaugmentation and biostimulation were used to remediate petroleum-contaminated
      soil which were collected from Zichang city in North of Shaanxi. The optimal
      bioremediation method was obtained by determining the total petroleum
      hydrocarbon(TPH) using the infrared spectroscopy. During the bioremediation,
      number of degrading strains, TPH catabolic genes, and soil microbial community
      diversity were determined by Most Probable Number (MPN), polymerase chain
      reaction (PCR) combined agarose electrophoresis, and PCR-denaturing gradient
      electrophoresis (DGGE). The results in different treatments showed different
      biodegradation effects towards total petroleum hydrocarbon (TPH). Biostimulation
      by adding N and P to soils achieved the best degradation effects towards TPH, and
      the bioaugmentation was achieved by inoculating strain SZ-1 to soils. Further
      analysis indicated the positive correlation between catabolic genes and TPH
      removal efficiency. During the bioremediation, the number of TPH and alkanes
      degrading strains was higher than the number of aromatic degrading strains. The
      results of PCR-DGGE showed microbial inoculums could enhance microbial community
      functional diversity. These results contribute to understand the ecologically
      microbial effects during the bioremediation of petroleum-polluted soil.

PMID- 26314141
TI  - [Enhanced Phytoextraction of Heavy Metals from Contaminated Soils Using Sedum
      alfredii Hance with Biodegradable Chelate GLDA].
AB  - Chemically enhanced phytoextraction by hyperaccumulator has been proposed as an
      effective approach to remove heavy metals from contaminated soil. Pot experiment
      was conducted to investigate the effect of application of the biodegradable
      chelate GLDA (L glutamic acid N,N-diacetic acid) at different doses or the
      combination of GLDA with EDTA (ethylenediamine tetraacetic acid) or CIT (citric
      acid) on the uptake of Cd, Zn and Pb by Sedum alfredii Hance (a Zn and Cd
      hyperaccumulator). Experimental results showed that GLDA addition to soil
      significantly increased the concentrations of Cd and Zn in Sedum alfredii Hance
      and its Cd and Zn phytoextraction compared to the control. Additionally, GLDA at
      2.5 mmol . kg(-1) resulted in the highest phytoextraction, being 2.5 and 2.6
      folds of the control for Cd and Zn, respectively. However, the combined
      application of GLDA + EDTA (1:1) and GLDA + CIT (1 :1 and 1:3) at a total dose of
      5 mmol . kg(-1) did not increase the phytoextraction of Zn and Cd, compared to
      the GLDA only treatment. Therefore, the biodegradable chelate GLDA could be
      regarded as a good chelate candidate for the phytoextraction of heavy metals of
      heavy metals from contaminated soils, particularly for Cd and Zn contaminated
      soils.

PMID- 26314142
TI  - [Speciation Characteristics and Bioavailability of Heavy Metals in Oasis Soil
      Under Pb, Zn Combined Stress].
AB  - Pot experiments were conducted on cole (Brassica) grown in oasis soil under
      combined stress of lead and zinc, to study the effect of heavy metal combined
      pollution on cole growth as well as the speciation conversion rules and
      bioavailability. The result showed that the promoting effect on cole growth was
      shown in the low concentration treatments, especially on stem leaves. With
      addition of exotic heavy metals, the main speciations of Pb and Zn in the soil
      transformed from tight-bound to loose-bound forms as compared to the control, and
      the bioavailability of heavy metals was increased. And, the exchangeable Pb and
      the carbonate bound form of Zn were the major contributing speciations which were
      absorbed in different parts of cole. What's more, the capabilities of uptake and
      translocation of Pb and Zn by cole were stronger at lower stress levels, and the
      enrichment and migration coefficients decreased with the increasing content of
      bioavailable fraction of the corresponding element or the coexisting element. In
      all treatments, the Pb concentration in the stem leaves of cole exceeded the food
      safety threshold, therefore it is recommended to conduct detection of relevant
      indicators before planting foliage vegetables in this kind of soil.

PMID- 26314144
TI  - [Effects of Ozone on Photosynthesis of Several Plants].
AB  - In order to investigate the effect of ozone on photosynthesis of Machilus pauhoi,
      Lindera setchuenensis, Phoebe bournei, Phoebe chekiangensis and Machilus
      thunbergii, the study was carried out in 12 open-top chambers( OTCs) with
      different levels of ozone in Qianyanzhou experimental station, and net
      photosynthesis rate (Pn) and stomatal conductance (Cond) were detected. The
      results indicated that ozone treatments changed the variation trend of
      photosynthesis of all tested plants, but ozone exposure did not always play an
      inhibitory role on them. In fact, photosynthesis changed with ozone
      concentration, experimental period, season and specific species. Exposed to ozone
      could even promote Pn to a peak in a short term, and the indicator of plants
      treated with ozone was higher than that of the control at this point. Low and
      medium concentrations of ozone treatment enhanced Pn of Phoebe bournei and
      Machilus thunbergii. The peak of treatment group also came earlier because of
      ozone. Furthermore, the positive correlation between Pn and Cond did not existed
      under the condition of ozone. Machilus thunbergii had the strongest resistance to
      ozone, followed by Phoebe bournei, by comparison, Phoebe chekiangensis, Machilus
      pauhoi and Lindera setchuenensis were more sensitive.

PMID- 26314143
TI  - [Influence of Sulfur on the Formation of Fe-Mn Plaque on Root and Uptake of Cd by
      Rice (Oryza sativa L.)].
AB  - A pool culture experiment using exogenous Cd-polluted paddy soils was carried out
      to investigate the influence of different forms of sulfur fertilizers (sulfur and
      gypsum) on the formation of Fe-Mn plaque on rice root and the uptake of Cd by
      rice. The results showed that the redox potential ( Eh) was about--200-100 mV,
      the pH was 6.9-7.9 and the pe + pH was 4-10 in different growth periods of rice.
      The mass fractions of Fe and Mn plaque on rice root were 5000-13,000 mg . kg(-1)
      and 170-580 mg . kg(-1), respectively. The high sulfur treatment led to the
      formation of more Fe plaque than the low sulfur treatment, and the mass fractions
      of Fe plaque in both treatments were 9400 mg . kg(-1) and 8600 mg . kg(-1)
      respectively in the boot stage. Contents of Mn plaque, significantly different in
      the tiller stage by elemental sulfur treatment and gypsum treatment, were 600 mg
      . kg(-1) and 400 mg . kg(-1), respectively. The elemental S treatment led to the
      formation of more Mn plaque on rice root than the gypsum treatment. The excessive
      intake of Fe2+ might be prevented by the formation of the plaque which had little
      significant influence on the uptake of Mn2+. The mass fractions of Cd adsorbed by
      rice roots surface plaque were 78.8-131.1 mg . kg(-1) in tiller stage, 16.6-21.1
      mg . kg(-1) in boot stage, and 3.0-9.2 mg . kg(-1) in mature stage. The high
      sulfur treatment led to higher adsorption of Cd by the plaque than the low sulfur
      treatment in the tiller stage and the boot stage, while opposite result was
      observed in the mature stage. The values of Cd on the plaque measured by ACA
      could not truly show its actual contents adsorbed. The mass fractions of Cd in
      the different parts of rice followed the order of roots > stem leaf > grain. The
      sulfur fertilizers applied significantly reduced the mass fractions of Cd uptake
      in different parts of rice, and the elemental sulfur treatment had better effects
      than the gypsum treatment before the mature stage in roots and stem leaf, and the
      gypsum sulfur treatment was better for grain. A certain amount of sulfur
      fertilizers could effectively prevent the migration of Cd from roots to stem and
      grain. The transfer coefficients of Cd from roots to stem leaf in the elemental
      sulfur treatment and the gypsum treatment were 0.13 and 0.25 in the boot stage,
      respectively, and the difference was significant. Elemental sulfur was more
      effective to prevent the Cd migration from roots to stem leaf, and the gypsum
      treatment was more active from roots to grain.

PMID- 26314145
TI  - [A Method Research on Environmental Damage Assessment of a Truck Rollover
      Pollution Incident].
AB  - With high occurrence of sudden water pollution incident, China faces an
      increasingly severe situation of water environment. In order to deter the acts of
      environmental pollution, ensure the damaged resources of environment can be
      restored and compensated, it is very critical to quantify the economic losses
      caused by the sudden water pollution incident. This paper took truck rollover
      pollution incidents in Chongqing for an example, established a set of evaluation
      method for quantifying the environmental damage, and then assessed the
      environmental damage by the method from four aspects, including the property
      damage, ecological environment and resources damages, the costs of administrative
      affairs in emergency disposal, and the costs of investigation and evaluation.

PMID- 26314146
TI  - [Some people do nothing - but they do it in a fascinating way].

PMID- 26314147
TI  - [The self-concept of children and adolescents with a chronic illness].

PMID- 26314148
TI  - [Herbal antibiotics: a gentle alternative?].

PMID- 26314149
TI  - [Media usage and passive smoking in preschool children: risk factors for
      cognitive development?].

PMID- 26314150
TI  - [On the movie: "Don't swallow it all". A film for psychotic patients, apparently
      health persons and specialty personnel].

PMID- 26314151
TI  - [Model project RAI reveals significant knowledge gaps in the use of antibiotics].

PMID- 26314152
TI  - [Do pregnant women need additional iodine?].

PMID- 26314153
TI  - [Everyone is talking about antibiotic resistance: what exactly is that?].

PMID- 26314154
TI  - [THE MICROSPORIDIUM GLUGEA GASTEROSTEI VORONIN 1974 (MICROSPORIDIA:
      MARINOSPORIDIA) FROM THE THREE-SPINED STICKLEBACK GASTEROSTEUS ACULEATUS
      (ACTINOPTERYGII: GASTEROSTEIFORMES) AS AN INDEPENDENT SPECIES].
AB  - The microsporidium Glugea gasterostei from the three-spined stickleback
      Gasterosteus aculeatus was described as an independent species basing upon
      morphological and ecological traits of the parasite (Voronin, 1974), further
      supported by ultrastructural characters of its spores (Voronin, 1983). During the
      revision of microsporidia of the genus Glugea (Canning, Lom, 1986; Lom, 2002),
      the validity of this species was doubted and it was synonymized with G. anomala.
      Nevertheless, the molecular phylogenetic analysis performed in the present study
      showed the unique molecular haplotype of small subunit rRNA gene of G.
      gasterostei (Genbank accession number KM977990) and its close relatedness to G.
      anomala, G. atherinae and G. hertwigi (sequence similarity of 99.7 %). One of
      typical characters of G. gasterostei, as opposed to G. anomala, is the formation
      of xenomas on inner tissues and not on the surface of infected fishes. This
      feature is retained even after the infection of different host species. Taken
      together, these data confirm the validity of G. gasterostei as a separate species
      among closely related taxa that had diverged comparatively recently.

PMID- 26314155
TI  - [COMPARATIVE ANALYSIS OF LIPID METABOLISM INDICES IN SOME PARASITES OF THE WHITE
      CHARR (SALVELINUS ALBUS) FROM THE LAKE KRINOTSKOE].
AB  - Comparative study of lipid metabolism indices (total lipids, separate lipid
      fractions, level of the lipid peroxidation processes, and antioxidant protection)
      was carried out in three parasite species collected from the white char in the
      Lake Kronotskoe: Diphyllobothrium ditremum Crepin, 1825 (Cestoda), Philonema
      oncorhynchi Kuitunen-Ekbaum, 1933 (Nematoda) H Neoechinorhynchus salmonis Ching,
      1984 (Acanthocephala). Acanthocephalans possessed significantly greater levels of
      total lipids, triacylglycerol, and malondialdehyde; nematodes, of cholesterol and
      sterol esters; and cestodes, in phospholipids and constants of the substrate
      oxidation. Dependence between lipid metabolism of helminths and their taxonomic
      affiliation, morpho-functional features, the stage of the life cycle, and the
      site of infection in the host are discussed.

PMID- 26314157
TI  - [VARIABILITY AND DETERMINING FACTORS OF THE BODY SIZE STRUCTURE OF THE
      INFRAPOPULATION OF COSMOCERCA ORNATA (NEMATODA: COSMOCERCIDAE) IN MARSH FROGS].
AB  - Variability of the body size in females of the Cosmocerca ornata (Dujardin,
      1845), a parasite of marsh frogs, is studied. The influence of both biotic (age,
      sex and a phenotype of the host, density of the parasite population) and abiotic
      (a season of the year, water temperature) factors on the formation of the body
      size structure in the C. ornata hemipopulation (infrapopulation) is demonstrated.
      The body size structure of the C. ornata hemipopulation is characterized by the
      low level of individual variability as within certain subpopulation groups of
      amphibians (sex, age and phenotype), so within the population of marsh frogs as a
      whole. The more distinct are the differences in biology and ecology of these host
      subpopulations, the more pronounced is the variability in the body size of C
      ornata.

PMID- 26314156
TI  - [HELMINTHS OF THE COMMON ROACH (RUTILUS RUTILUS LINNAEUS, 1758) AND THE EUROPEAN
      PERCH (PERCA FLUVIALITIS LINNAEUS, 1758) IN THE LAKE TERKHIIN TSAGAAN
      (MONGOLIA)].
AB  - The article provides data about helminthes of the common roach and the European
      perch in the Lake Terkhiin Tsagaan (Mongolia). Six parasite species were found.
      Data on the occurrence of the trematode species and larvae of Streptocara
      crassicauda are obtained for the first time. Species composition of Diplostomum
      spp. metacercariae parasitizing in fish eyes is updated.

PMID- 26314158
TI  - [NEW FINDINGS OF BAT ECTOPARASITES (CHIROPTERA: VESPERTILIONIDAE) IN SOUTHERN
      SIBERIA].
AB  - The data on new findings of ectoparasites (mites and insects) of bats
      (Chiroptera: Vespertilionidae) in the Western Sayan and Tuva are represented. The
      bat fly Basilia mongolensis mongolensis Theodor, 1966 was discovered in the
      territory of Russia for the first time. Gamasid mite Spinturnix bregetovae
      Stanyukovich, 1995 is new for the region. New hosts were described for some
      ectoparasites.

PMID- 26314159
TI  - [REACTION OF HAEMOCYTES OF THE MOLLUSK PLANORBARIUS CORNEUS TO A XENOTRANSPLANT].
AB  - Tissue reaction of the mollusk Planorbarius corneus to the introduction of a
      transplant (cat vibrissa) was examined. The transplant was introduced into
      mollusk tissues with the use of an injection needle. After a day, flattened
      haemocytes were found on the surface of the transplant. The wound channel formed
      by the needle was arrested by a capsule formed of 5-15 layers of flattened cells.
      The cavity of the wound channel and the core of the vibrissa were also filled
      with haemocytes. During incubation of the vibrissa in vitro, adhesion and
      sedimentation of haemocytes on its surface was observed.

PMID- 26314160
TI  - [Remorse and regret about becoming a mother].

PMID- 26314161
TI  - [Prevention in susceptibility to atopic dermatitis: daily skin care from the
      beginning supports healthy skin development].

PMID- 26314162
TI  - [Foreign travel with children - possible, but only with good preparation!].

PMID- 26314163
TI  - [Health problems and problems in the health care system in China: impressions of
      a physician after 6 China trips].

PMID- 26314165
TI  - [New school subject: headache].

PMID- 26314166
TI  - [Personnel staff in the neonatal department: effect on complications and
      mortality? Recent study documents disappointing results].

PMID- 26314167
TI  - [Vitamin D - a valuable protective shield].

PMID- 26314168
TI  - [If not now, then when?! Mandatory vaccination for children in group facilities
      must finally be implemented].

PMID- 26314169
TI  - [New guidelines for mucoviscidosis nursing are here!].

PMID- 26314170
TI  - [Natural childbirth: do maternal microbes prevent asthma?].

PMID- 26314171
TI  - [Early day care: federal quality regulation is necessary].

PMID- 26314172
TI  - [No scratching, please: 6 strategies to control neurodermatitis itch].

PMID- 26314173
TI  - Benchmarking VNA Adoption.

PMID- 26314174
TI  - New Directions in CMS Bundling. 2015 Update.

PMID- 26314175
TI  - Workplace Bullying in Healthcare: Part 3.
AB  - As many as 53.5 million American workers have experienced workplace bullying,
      which can cost organizations an estimated $200 billion annually in lost
      productivity, increased sick d ays, increased med ical claims, legal costs, and
      staff turnover. Bullying can occur in any profession, but for many reasons it is
      most prevalent in healthcare. Bullying behavior in healthcare has been reported
      and documented in literature for over 35 years. Although physicians are often
      considered to be the primary culprit of bullying, healthcare bullies can be one
      any one of the professionals who work in the organization including nurses,
      radiology technologists, pharmacists, ancillary staff personnel, administrators,
      or other non-physician staff members. The first installment of the series focused
      on defining bullying and its impact on the organization. Part 2 discussed three
      legal protections for the bully to include at-will laws, unions, and bylaws
      related to physician privileging. The final installment in this series will
      evaluate specific bully types and implementing processes to address inappropriate
      behavior.

PMID- 26314176
TI  - It's the People.

PMID- 26314178
TI  - Justify a Dedicated Radiology Coder-Reimbursement Specialist.
AB  - There are many opportunities to justify a dedicated staff member. We have to be
      able to answer the question "How does this position make money?" The bottom line
      is that it's crucial the facility does not forfeit appropriate reimbursement for
      its existing procedures. For new procedures, or equipment, this individual can
      also ensure cost-benefit analysis/ROI is correct for equipment and/or supply
      purchases. The specific opportunities vary by facility so you must determine
      where your potential opportunities lie. There is not one answer, but this article
      provides you with specific areas to evaluate. Keep in mind if you are evaluating
      opportunities related to specific procedures you need to utilize outpatient
      numbers and assume Medicare reimbursement rates so that you calculate a
      conservative estimate. There is nioney to be found in most hospital
      organizations, so take the time to identify the potential benefit for your own.
      You can quantify the impact of a dedicated individual based on your specific case
      mix, which is very useful when justifying a new position. Also, it's very
      important to remember, you get what you pay for-fill the new position wisely.
      Saving a small amount in salary may result in a large sacrifice in potential
      revenues.

PMID- 26314177
TI  - Challenging the Service Cost Paradigm.
AB  - Most healthcare organizations are looking to find more efficient and cost
      effective ways of delivering service as they are challenged to assume more risk
      in order to provide timely and cost effective care. Alternative service with an
      independent service organization or third party may be an easy and rewarding
      solution. Serious consideration should be given purchase/service cycle and into a
      lower cost service paradigm designed to provide excellent service tailored to a
      facility's specific needs. In this article, an evaluation of all service model
      options is provided, as well as examples including a CT acquisition, pro formas,
      and program development.

PMID- 26314179
TI  - lCD-10: Initial vs. Subsequent Encounter.

PMID- 26314180
TI  - CT Lung Cancer Screening Program Development: Part 2.
AB  - Radiology administrators must use innovative strategies around clinical
      collaboration and marketing to ensure that patients access the service in
      sufficient numbers. Radiology Associates of South Florida in collaboration with
      Baptist Health South Florida have developed a successful lung cancer screening
      program. The biggest factors in their success have been the affordability of
      their service and the quality of the program. Like mammography, lung cancer
      screening programs serve as an entry point to other services that generate
      revenue for the hospital. Patients may require further evaluation in the form of
      more imaging or surgical services for biopsy. Part 1 provided background and laid
      out fundamentals for starting a program. Part 2 focuses on building patient
      volume, marketing, and issues related to patient management after the screen is
      performed.

PMID- 26314181
TI  - Lean: "You're Stealing My Creativity!".

PMID- 26314182
TI  - Managing Generational Differences in Radiology.
AB  - Diversity can take many forms. One type of recent focus is generational
      differences and intergenerational issues. Much research exists regarding
      generational differences in the workplace and in healthcare as a whole. Very
      little has been done on generational differences within the field of radiology.
      An analysis of current research of generational differences within radiology,
      nursing, and healthcart in general was performed to identify current trends and
      establish similarities and discordance in available studies. An emphasis was
      placed on how generational differences influence education, teamwork, and patient
      care, along with what challenges and opportunities exist for managers, leaders,
      and organizations.

PMID- 26314183
TI  - Appreciation.

PMID- 26314184
TI  - President's Update. Make your vote count.

PMID- 26314185
TI  - Practice consultations--A Year in Review.

PMID- 26314186
TI  - Workplace absences: Can occupational health nurses be the leaders of charge?

PMID- 26314187
TI  - Current studies can help shape the future of health care for older adults.

PMID- 26314188
TI  - Leading change. RNs at Killam Alberta Continuing Care embrace full scope of
      practice.

PMID- 26314189
TI  - Prioritizing Pressure Ulcer prevention.

PMID- 26314190
TI  - Perpectives on Bullying. A qualitative study into academic incivility among
      nursing students.

PMID- 26314192
TI  - The art of healing.

PMID- 26314191
TI  - Attachment: a connection for life. Child and adolescent mental health
      professionals heal families through learning.

PMID- 26314193
TI  - Legal Risks of Email--Part 1. Privacy Concerns.

PMID- 26314194
TI  - Closing Perspectives: Lets implement Alberta's Primary Health Care Strategy
      without delay.

PMID- 26314195
TI  - Letter by Huang regarding the article, "Statin use increases the risk of
      depressive disorder in stroke patients: A population-based study".

PMID- 26314196
TI  - The utility of alpha-synuclein as biofluid marker in neurodegenerative diseases:
      a systematic review of the literature.
AB  - The discovery of alpha-synuclein (alpha-syn) as a major component of Lewy bodies,
      neuropathological hallmark of Parkinson's disease (PD), dementia with Lewy bodies
      and of glial inclusions in multiple system atrophy initiated the investigation of
      alpha-syn as a biomarker in cerebrospinal fluid (CSF). Due to the involvement of
      the periphery in PD the quantification of alpha-syn in peripheral fluids such as
      serum, plasma and saliva has been investigated as well. We review how the
      development of multiple assays for the quantification of alpha-syn has yielded
      novel insights into the variety of alpha-syn species present in the different
      fluids; the optimal preanalytical conditions required for robust quantification
      and the potential clinical value of alpha-syn as biomarker. We also suggest
      future approaches to use of CSF alpha-syn in neurodegenerative diseases. 

PMID- 26314197
TI  - Role of NK cells in immunotherapy and virotherapy of solid tumors.
AB  - Although natural killer (NK) cells are endowed with powerful cytolytic activity
      against cancer cells, their role in different therapies against solid tumors has
      not yet been fully elucidated. Their interactions with various elements of the
      tumor microenvironment as well as their possible effects in contributing to
      and/or limiting oncolytic virotherapy render this potential immunotherapeutic
      tool still difficult to exploit at the bedside. Here, we will review the current
      literature with the aim of providing new hints to manage this powerful cell type
      in future innovative therapies, such as the use of NK cells in combination with
      new cytokines, specific mAbs (inducing ADCC), Tyr-Kinase inhibitors,
      immunomodulatory drugs and/or the design of oncolytic viruses aimed at optimizing
      the effect of NK cells in virotherapy. 

PMID- 26314198
TI  - miR-106a* inhibits the proliferation of esophageal carcinoma cells by targeting
      CDK2-associated Cullin 1 (CACUL1).
AB  - Previous studies suggest that aberrant microRNA expression is common in plenty of
      cancers. The expression of miR-106a* was decreased in follicular lymphoma, but
      the expression and functions of miR-106a* in esophageal carcinoma (EC) remain
      unclear. In this study, we explored the expression and anti-oncogenic roles of
      miR-106a* in human EC. The expression of miR-106a* is significantly decreased in
      EC tissues and EC cell lines. Overexpression of miR-106a* suppressed EC cell
      proliferation, clonogenicity, G1/S transition, and induced apoptosis in vitro,
      but inhibition of miR-106a* facilitated cell proliferation, clonogenicity, G1/S
      transition. Luciferase reporter assay results showed that CDK2-associated Cullin
      1 (CACUL1) was a direct target of miR-106a* in EC cells. Moreover, silencing
      CACUL1 resulted in the same biologic effects of miR-106a* overexpression in EC
      cells, which included suppressed EC cell proliferation, clonogenicity, and
      blocked G1/S transition through CDK2 pathway by inhibiting cell cycle regulators
      (Cyclin A, Cyclin E). Our data indicate that miR-106a* might play an anti
      oncogenic role in EC by regulating CACUL1 expression, which suggest miR-106a* as
      a new potential diagnostic and therapeutic target for EC.

PMID- 26314199
TI  - Genetics and evolution of plumage color in Crested Ibis: Analysis of the
      melanocortin-1 receptor (MC1R).
AB  - The melanocortin-1-recepter gene (MC1R), an important regulator in melanin
      synthesis, may cause different plumage color patterns in birds: gain-of-function
      mutations lead to the synthesis of eumelanin, whereas loss-of-function mutations
      help to generate pheomelanin synthesis. We had chosen MC1R as a candidate gene
      for the depigmentation of crested ibis, cloned and sequenced the crested ibis
      MC1R gene the first time. The crested ibis MC1R sequence, highly conserved with
      other birds during evolution, had seven transmembrane domains which played an
      indispensable function through evolution. We did not found any substitution on
      this sequence among all the sample individuals. The phylogenetic tree showed that
      crested ibis separated early in the evolution of birds. TYR, TYRP1, TYRP2 and
      MC1R were expressed in blood and the expression of the four genes showed no
      significant difference (p>0.05) between normal and albinism individuals, and this
      result demonstrated that melanic pigments are not involved in the production of
      red pigmentation in birds. Further study of the crested ibis albinism should
      focus on analyzing carotenoid-based genes.

PMID- 26314200
TI  - The association of ApE1 -656T>G and 1349T>G polymorphisms with breast cancer
      susceptibility in northern Iran.
AB  - Breast cancer is the most common cancer and one of the main causes of cancer
      related death in the world and has become a major public health concern. Many
      genes have been shown to be involved in the progress of the breast cancer. Human
      apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional protein that has
      an important role in the base excision repair (BER) pathway. The aim of this
      study was to evaluate the association between ApE1 -656T>G and 1349T>G
      polymorphisms and the susceptibility to breast cancer in northern Iran
      population. Samples were obtained from 150 patients diagnosed with breast cancer
      and 150 control subjects and genotyped by tetra - primer amplification refractory
      mutation system PCR (T-ARMS-PCR). We observed a significant difference in
      genotype distributions of -656T>G polymorphism between patients and controls (P=
      0.03). Findings indicated that individuals with the variant TG genotypes had a
      significant decreased risk of breast cancer (OR= 0.55, 95% CI= 0.33 - 0.91, P=
      0.019). However, the significant association between 1349T>G polymorphism and
      breast cancer risk was not observed (P = 0.89). Larger studies are needed to
      confirm our results.

PMID- 26314201
TI  - Delayed resolution of syrinx after posterior fossa decompression without dural
      opening in children with Chiari malformation Type I.
AB  - OBJECT Chiari malformation Type I (CM-I) is associated with a syrinx in 25%-85%
      of patients. Although posterior fossa decompression (PFD) without dural opening
      is an accepted treatment option for children with symptomatic CM-I, many surgeons
      prefer to open the dura if a syrinx exists. The purpose of this study was to
      investigate the frequency and timing of syrinx resolution in children undergoing
      PFD without dural opening for CM-I. METHODS A retrospective review of 68
      consecutive pediatric patients with CM-I and syringomyelia who underwent PFD
      without dural opening was conducted. Patient demographics, presenting symptoms
      and signs, radiographic findings, and intraoperative ultrasound and
      neuromonitoring findings were studied as well as the patients' clinical and
      radiographic follow-up. RESULTS During the mean radiographic follow-up period of
      32 months, 70% of the syringes improved. Syrinx improvement occurred at a mean of
      31 months postoperatively. All patients experienced symptom improvement within
      the 1st year, despite only 26% of patients showing radiographic improvement
      during that period. Patients presenting with sensory symptoms or motor weakness
      had a higher likelihood of having radiographic syrinx improvement
      postoperatively. CONCLUSIONS In children with CM-I and a syrinx undergoing PFD
      without dural opening, syrinx resolution occurs in approximately 70% of patients.
      Radiographic improvement of the syrinx is delayed, but this does not correlate
      temporally with symptom improvement. Sensory symptoms or motor weakness on
      presentation are associated with syrinx resolution after surgery.

PMID- 26314202
TI  - Use of a formal assessment instrument for evaluation of resident operative skills
      in pediatric neurosurgery.
AB  - OBJECT Currently there is no standardized tool for assessment of neurosurgical
      resident performance in the operating room. In light of enhanced requirements
      issued by the Accreditation Council for Graduate Medical Education's Milestone
      Project and the Matrix Curriculum Project from the Society of Neurological
      Surgeons, the implementation of such a tool seems essential for objective
      evaluation of resident competence. Beyond compliance with governing body
      guidelines, objective assessment tools may be useful to direct early intervention
      for trainees performing below the level of their peers so that they may be given
      more hands-on teaching, while strong residents can be encouraged by faculty
      members to progress to conducting operations more independently with passive
      supervision. The aims of this study were to implement a validated assessment tool
      for evaluation of operative skills in pediatric neurosurgery and determine its
      feasibility and reliability. METHODS All neurosurgery residents completing their
      pediatric rotation over a 6-month period from January 1, 2014, to June 30, 2014,
      at the authors' institution were enrolled in this study. For each procedure,
      residents were evaluated by means of a form, with one copy being completed by the
      resident and a separate copy being completed by the attending surgeon. The
      evaluation form was based on the validated Objective Structured Assessment of
      Technical Skills for Surgery (OSATS) and used a 5-point Likert-type scale with 7
      categories: respect for tissue; time and motion; instrument handling; knowledge
      of instruments; flow of operation; use of assistants; and knowledge of specific
      procedure. Data were then stratified by faculty versus resident (self-)
      assessment; postgraduate year level; and difficulty of procedure. Descriptive
      statistics (means and SDs) were calculated, and the results were compared using
      the Wilcoxon signed-rank test and Student t-test. A p value < 0.05 was considered
      statistically significant. RESULTS Six faculty members, 1 fellow, and 8 residents
      completed evaluations for 299 procedures, including 32 ventriculoperitoneal (VP)
      shunt revisions, 23 VP shunt placements, 19 endoscopic third ventriculostomies,
      and 18 craniotomies for tumor resection. There was no significant difference
      between faculty and resident self-assessment scores overall or in any of the 7
      domains scores for each of the involved residents. On self-assessment, senior
      residents scored themselves significantly higher (p < 0.02) than junior residents
      overall and in all domains except for "time and motion." Faculty members scored
      senior residents significantly higher than junior residents only for the
      "knowledge of instruments" domain (p = 0.05). When procedure difficulty was
      considered, senior residents' scores from faculty members were significantly
      higher (p = 0.04) than the scores given to junior residents for expert procedures
      only. Senior residents' self-evaluation scores were significantly higher than
      those of junior residents for both expert (p = 0.03) and novice (p = 0.006)
      procedures. CONCLUSIONS OSATS is a feasible and reliable assessment tool for the
      comprehensive evaluation of neurosurgery resident performance in the operating
      room. The authors plan to use this tool to assess resident operative skill
      development and to improve direct resident feedback.

PMID- 26314203
TI  - Editorial: Measuring resident operative skills.

PMID- 26314204
TI  - Letter to the Editor: Carbon dioxide laser and corpus callosotomy.

PMID- 26314205
TI  - Preoperative ultrasound localization of the lambda in patients with
      scaphocephaly: a technical note for minimally invasive craniectomy.
AB  - Sagittal craniosynostosis, the most common single suture craniosynostosis, is
      treated by numerous surgical techniques. Minimally invasive endoscopy-assisted
      procedures with postoperative helmeting are being used with reports of good
      cosmetic outcomes with decreased morbidity, shortened hospital stay, and less
      blood loss and transfusion. This procedure uses small skin incisions, which must
      be properly placed to provide safe access to the posterior sagittal and lambdoid
      sutures. However, the lambda is often hard to palpate through the skin due to the
      abnormal head shape. The authors describe their experience with the use of
      intraoperative, preincision ultrasound localization of the lambda in patients
      with scaphocephaly undergoing a minimally invasive procedure. This simple
      technique can also be applied to other operations where proper identification of
      the cranial sutures is necessary.

PMID- 26314206
TI  - Treatment of posthemorrhagic ventricular dilation in preterm infants: a
      systematic review and meta-analysis of outcomes and complications.
AB  - OBJECT The optimal clinical management of intraventricular hemorrhage (IVH) and
      posthemorrhagic ventricular dilation (PHVD)/posthemorrhagic hydrocephalus (PHH)
      in premature infants remains unclear. A common approach involves temporary
      treatment of hydrocephalus in these patients with a ventriculosubgaleal shunt
      (VSGS), ventricular access device (VAD), or external ventricular drain (EVD)
      until it becomes evident that the patient needs and can tolerate permanent CSF
      diversion (i.e., ventriculoperitoneal shunt). The present systematic review and
      meta-analysis aimed to provide a robust and comprehensive summary of the
      published literature regarding the clinical outcomes and complications of these 3
      techniques as temporizing measures in the management of prematurity-related
      PHVD/PHH. METHODS The authors searched MEDLINE, EMBASE, CINAHL, Google Scholar,
      and the Cochrane Library for studies published through December 2013 on the use
      of VSGSs, VADs, and/or EVDs as temporizing devices for the treatment of
      hydrocephalus following IVH in the premature neonate. Data pertaining to patient
      demographic data, study methods, interventions, and outcomes were extracted from
      eligible articles. For each of the 3 types of temporizing device, the authors
      performed meta-analyses examining 6 outcomes of interest, which were rates of 1)
      obstruction; 2) infection; 3) arrest of hydrocephalus (i.e., permanent shunt
      independence); 4) mortality; 5) good neurodevelopmental outcome; and 6) revision.
      RESULTS Thirty-nine studies, representing 1502 patients, met eligibility
      criteria. All of the included articles were observational studies; 36 were
      retrospective and 3 were prospective designs. Nine studies (n = 295) examined
      VSGSs, 24 (n = 962) VADs, and 9 (n = 245) EVDs. Pooled rates of outcome for VSGS,
      VAD, and EVD, respectively, were 9.6%, 7.3%, and 6.8% for obstruction; 9.2%,
      9.5%, and 6.7% for infection; 12.2%, 10.8%, and 47.3% for revision; 13.9%, 17.5%,
      and 31.8% for arrest of hydrocephalus; 12.1%, 15.3%, and 19.1% for death; and
      58.7%, 50.1%, and 56.1% for good neurodevelopmental outcome. CONCLUSIONS This
      study provides robust estimates of outcomes for the most common temporizing
      treatments for IVH in premature infants. With few exceptions, the range of
      outcomes was similar for VSGS, VAD, and EVD.

PMID- 26314209
TI  - Encephalitis due to ovarian dermoid.

PMID- 26314207
TI  - Essential role of D1R in the regulation of mTOR complex1 signaling induced by
      cocaine.
AB  - The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that is
      involved in neuronal adaptions that underlie cocaine-induced sensitization and
      reward. mTOR exists in two functionally distinct multi-component complexes known
      as mTORC1 and mTORC2. In this study, we show that increased mTORC1 activity
      induced by cocaine is mediated by the dopamine D1 receptor (D1R). Specifically,
      cocaine treatment increased the phosphorylation on residues Thr2446 and Ser2481
      but not on Ser2448 in the nucleus accumbens (NAc) and that this increase in
      phosphorylated mTOR levels was also apparent when complexed with its binding
      partner Raptor. Furthermore, the increase in phosphorylated mTOR levels, as well
      as phosphorylated 4E-BP1 and S6K, downstream targets of mTORC1 were blocked with
      SCH23390 treatment. Similar results were also observed in the dopamine
      transporter knockout mice as the increase in phosphorylated mTOR Thr2446 and
      Ser2481 was blocked by SCH23390 but not with raclopride. To further validate D1R
      role in mTORC1 signaling, decrease in phosphorylated mTOR levels were observed in
      D1R knockout mice, whereas administration of SKF81297 elevated phosphorylated
      mTOR in the NAc. Lastly deletion of mTOR or Raptor in D1R expressing neurons
      reduced cocaine-induced locomotor activity. Together, our data supports a
      mechanism whereby mTORC1 signaling is activated by cocaine administration through
      the stimulation of D1R. 

PMID- 26314208
TI  - NPY Y2 receptors in the central amygdala reduce cued but not contextual fear.
AB  - The amygdala is fundamental for associative fear and extinction learning.
      Recently, also the central nucleus of the amygdala (CEA) has emerged as a site of
      plasticity actively controlling efferent connections to downstream effector brain
      areas. Although synaptic transmission is primarily mediated by glutamate and
      GABA, neuropeptides critically influence the overall response. While neuropeptide
      Y (NPY) acting via postsynaptic Y1 receptors exerts an important anxiolytic and
      fear-reducing action, the role of the predominantly presynaptic Y2 receptors is
      less defined. To investigate the role of Y2 receptors in the CEA we employed
      viral-vector mediated over-expression of the Y2 selective agonist NPY3-36 in fear
      conditioning and extinction experiments. NPY3-36 over-expression in the CEA
      resulted in reduced fear expression during fear acquisition and recall.
      Interestingly, this effect was blocked by intraperitoneal injection of a brain
      penetrant Y2 receptor antagonist. Furthermore, over-expression of NPY3-36 in the
      CEA also reduced fear expression during fear extinction of CS-induced but not
      context-related fear. Again, fear extinction appeared delayed by peripheral
      injection of a Y2 receptor antagonist JNJ-31020028. Importantly, mice with over
      expression of NPY3-36 in the CEA also displayed reduced spontaneous recovery and
      reinstatement, suggesting that Y2 receptor activation supports a permanent
      suppression of fear. Local deletion of Y2 receptors in the CEA, on the other
      hand, increased the expression of CS-induced freezing during fear recall and fear
      extinction. Thus, NPY inhibits fear learning and promotes cued extinction by
      reducing fear expression also via activation of presynaptic Y2 receptors on CEA
      neurons. 

PMID- 26314210
TI  - Nickel-supported carbon nitride photocatalyst combined with organic dye for
      visible-light-driven hydrogen evolution from water.
AB  - A noble-metal-free photocatalytic H2 production system consisting of a Ni-based
      catalyst, visible-light-responsive organic dye, and graphitic carbon nitride (g
      C3N4) as a support has been developed. Characterization by means of XAFS revealed
      that the deposition of a trinuclear Ni precursor complex, Ni(NiL2)2Cl2 (L = beta
      mercaptoethylamine), on the g-C3N4 affords a monomeric Ni(ii) species involving
      beta-mercaptoethylamine and aqua ligands in an octahedral coordination geometry.
      Such a Ni species acts as a hydrogen production site from an aqueous solution
      without an electron relay reagent by combining with thiazole orange (TO) as a
      photosensitizer. The emission of the attached TO at around 550 nm decreases with
      increasing loading amount of Ni catalyst, suggesting electron transfer from TO to
      the Ni catalyst via the g-C3N4 support. Leaching and agglomeration of the active
      Ni catalyst and TO are not observed during the photocatalytic reaction. Moreover,
      the use of highly porous carbon nitride (nanoporous carbon nitride; nanoC3N4) is
      proven to significantly enhance the photocatalytic activity because of the high
      surface area due to the unique porous structure as well as high absorption and
      emission properties of TO associated with nanoC3N4. 

PMID- 26314211
TI  - Baseline Evaluation With a Sweating Thermal Manikin of Personal Protective
      Ensembles Recommended for Use in West Africa.
AB  - OBJECTIVE: Experience with the use of personal protective equipment (PPE)
      ensembles by health care workers responding to the Ebola outbreak in the hot,
      humid conditions of West Africa has prompted reports of significant issues with
      heat stress that has resulted in shortened work periods. METHODS: A sweating
      thermal manikin was used to ascertain the time to achievement of a critical core
      temperature of 39  degrees C while wearing 4 different PPE ensembles similar to
      those recommended by the World Health Organization and Medecins Sans Frontieres
      (Doctors Without Borders) at 2 different ambient conditions (32  degrees C/92%
      relative humidity and 26  degrees C/80% relative humidity) compared with a
      control ensemble. RESULTS: PPE ensembles that utilized coveralls with moderate to
      high degrees of impermeability attained the critical core temperature in
      significantly shorter times than did other ensembles. Encapsulation of the head
      and neck region resulted in higher model-predicted subjective impressions of heat
      sensation. CONCLUSIONS: To maximize work capacity and to protect health care
      workers in the challenging ambient conditions of West Africa, consideration
      should be given to adjustment of work and rest schedules, improvement of PPE
      (e.g., using less impermeable and more breathable fabrics that provide the same
      protection), and the possible use of cooling devices worn simultaneously with
      PPE.

PMID- 26314212
TI  - Bulged Invader probes: activated duplexes for mixed-sequence dsDNA recognition
      with improved thermodynamic and kinetic profiles.
AB  - Double-stranded oligonucleotides with +1 interstrand zipper arrangements of
      intercalator-functionalized nucleotides are energetically activated for
      recognition of mixed-sequence double-stranded DNA. Incorporation of nonyl (C9)
      bulges at specific positions of these probes, results in more highly affine (>5
      fold), faster (>4-fold) and more persistent dsDNA recognition relative to
      conventional Invader probes. 

PMID- 26314213
TI  - Effect of lipid emulsion during resuscitation of a patient with cardiac arrest
      after overdose of chlorpromazine and mirtazapine.
AB  - No specific treatment exists for poisoning with most fat-soluble drugs.
      Intravenous lipid emulsion (ILE) may be effective therapy against such drugs, but
      effects of ILE treatment are unclear. A 24-year-old woman with depression seen
      sleeping in the morning was found comatose in the evening, and an emerging
      lifesaving technologies service was called. After emerging lifesaving
      technologies departure to hospital, she stopped breathing, became pulseless, and
      cardiopulmonary life support was started immediately. Electrocardiographic
      monitoring showed asystole during resuscitation even after arrival at hospital.
      Empty packaging sheets of 60-tablet chlorpromazine (CPZ) (50 mg/tablet) and 66
      tablet mirtazapine (MZP) (15 mg/tablet) found at the scene suggested drug-related
      cardiopulmonary arrest. Along with conventional administration of adrenaline
      (total dose, 5 mg), 20% Intralipid 100 mLwas given intravenously 8 minutes after
      hospital arrival and readministered 27 minutes after hospital arrival because of
      continued asystole. Return of spontaneous circulation occurred 29 minutes after
      arrival (70 minutes after cardiac arrest). The patient recovered without any
      major complications and was transferred to another hospital for psychiatric
      treatment 70 days after admission. Concentrations of CPZ and MZP were still high
      when return of spontaneous circulation was achieved with ILE. This case suggested
      the possible benefit of ILE in treating life threatening cardiotoxicity from CPZ
      and MZP overdose.

PMID- 26314214
TI  - Extracorporeal life support for cardiac arrest in a 13-year-old girl caused by
      Wolff-Parkinson-White syndrome.
AB  - Generally, Wolff-Parkinson-White (WPW) syndrome presents good prognosis. However,
      several case reports demonstrated malignant arrhythmia or sudden cardiac death as
      WPW syndrome's first presentation. Cardiopulmonary resuscitation using
      extracorporeal life support is a therapeutic option in refractory cardiac arrest.
      We present a WPW syndrome patient who had sudden cardiac arrest as the first
      presentation of the disease and treated it using extracorporeal life support with
      good neurologic outcome.

PMID- 26314215
TI  - Randomized single-blinded clinical trial on effects of nursery songs for infants
      and young children's anxiety before and during head computed tomography.
AB  - OBJECTIVE: The objective of this clinical trial was to determine if an
      intervention of listening to nursery songs with integrated heartbeat sounds
      resulted in changes in anxiety levels in infants and children younger than 4
      years in an emergent setting. METHODS: This is a randomized single-blinded
      controlled trial. The study included 62 children younger than 4 years who were
      deemed by the emergency physician to need a computed tomographic (CT) scan. The
      experimental group (Exp) (n=30) listened to recorded children's songs with
      integrated heartbeat sounds (Baby Go To Sleep compact disc) before and during the
      head CT. The controls (Con) (n=32) had no music. Two scales to measure agitation
      were completed by a trained research associate: (1) a 10-cm visual analog scale
      (VAS) and (2) the Modified Ramsay Sedation Scale (MRSS). The research associate
      wore headphones blocking out all music. The research associate recorded agitation
      levels preintervention and postintervention on the 2 scales, whether there was
      successful completion of the head CT without pharmacologic intervention, and the
      frequency of medication use. Mann-Whitney U, t test, and logistic regression were
      used for analysis, and P<.05 was considered significant. RESULTS: There were no
      differences between groups in the age, sex, initial vital signs, diagnostic
      category, ethnicity, insurance status, rate of completion of head CT, rate of
      medication use, hospital admissions, or initial VAS or MRSS score. There was
      improvement on the VAS score in 53% of the Exp group subjects and 25% of the Con
      group subjects. The VAS score in the Exp group improved by 1.6 cm, whereas the
      Con group worsened by 0.8 cm after the intervention (difference=2.4 cm, P=.03).
      There were no significant changes in MRSS scores. Accounting for age, sex, and
      admission status, the adjusted odds of having an improved sedation score were 3.2
      (1.0-9.7) in the Exp group. CONCLUSION: Measured on a VAS, there was a
      significant decrease in agitation in children undergoing a head CT when
      children's songs with integrated heartbeat sounds were played before and during
      the procedure.

PMID- 26314216
TI  - Isolated abducens nerve palsy due to pituitary apoplexy after mild head trauma.
AB  - Pituitary apoplexy is a relatively rare condition. Cranial nerve palsies may
      develop due to compression of the surrounding structures by the rapidly expanding
      tumor. While the most commonly affected nerve is the oculomotor nerve, abducens
      nerve palsy may also occur less commonly. A 68-year-old male patient was admitted
      to the emergency department with complaints of severe headache, nausea, vomiting,
      and diplopia after head trauma due to falling. His magnetic resonance imaging
      evaluation demonstrated a large pituitary adenoma and bleeding into the tumor,
      which was acutely expanding and leading to compression of the abducens nerve
      laterally. Isolated abducens palsy due to posttraumatic pituitary apoplexy is a
      rare clinical condition, and as the symptoms and signs are nonspecific, it can
      commonly remain clinically undiagnosed. In this article, our aim was to draw
      attention to a clinical condition in which unfavorable complications may develop
      if the diagnosis is overlooked.

PMID- 26314217
TI  - A calvarial acute subdural hematoma migrating into the spinal canal in a young
      male.
AB  - It is not common for an acute subdural hematoma (SDH) in the supratentorial
      region to show rapid resolution or migration during the clinical course. In this
      report, we present a rare case where the SDH in the supratentorial region was
      observed to rapidly migrate into the lumbar spinal canal, leading to severe
      radiculopathy. A 20-year-old male patient was admitted to the emergency
      department with severe headache after head trauma. The patient's overall
      condition was good, whereas his Glasgow Coma Scale score was 15 and blood
      pressure was normal. He had vomited 3 times after the onset of pain. No stiff
      neck was found, and the computed tomography showed an ASDH over the outer layer
      of the right hemisphere, causing a 7- to 8-mm shift. During the follow-up, the
      headache regressed and eventually resolved after 12 hours; however, another
      severe pain occurred in the lumbar region and in both legs. The pain worsened
      over time, progressing to sciatica in both legs. Acute SDH associated with a
      minor head trauma may migrate from the supratentorial compartment into the spinal
      canal by the help of elastic cerebral tissues in young adults and children.

PMID- 26314218
TI  - Vorinostat, a histone deacetylase (HDAC) inhibitor, promotes cell cycle arrest
      and re-sensitizes rituximab- and chemo-resistant lymphoma cells to chemotherapy
      agents.
AB  - PURPOSE: Preclinical models of chemotherapy resistance and clinical observations
      derived from the prospective multicenter phase III collaborative trial in
      relapsed aggressive lymphoma (CORAL) study demonstrated that primary
      refractory/relapsed B cell diffuse large B cell lymphoma has a poor clinical
      outcome with current available second-line treatments. Preclinically, we found
      that rituximab resistance is associated with a deregulation on the mitochondrial
      potential rendering lymphoma cells resistant to chemotherapy-induced apoptotic
      stimuli. There is a dire need to develop agents capable to execute alternative
      pathways of cell death in an attempt to overcome chemotherapy resistance.
      Posttranscriptional histone modification plays an important role in regulating
      gene transcription and is altered by histone acetyltransferases (HATs) and
      histone deacetylases (HDACs). HDACs regulate several key cellular functions,
      including cell proliferation, cell cycle, apoptosis, angiogenesis, migration,
      antigen presentation, and/or immune regulation. Given their influence in multiple
      regulatory pathways, HDAC inhibition is an attractive strategy to evaluate its
      anti-proliferation activity in cancer cells. To this end, we studied the anti
      proliferation activity and mechanisms of action of suberoylanilide hydroxamic
      acid (SAHA, vorinostat) in rituximab-chemotherapy-resistant preclinical models.
      METHODS: A panel of rituximab-chemotherapy-sensitive (RSCL) and rituximab
      chemotherapy-resistant cell lines (RRCL) and primary tumor cells isolated from
      relapsed/refractory B cell lymphoma patients were exposed to escalating doses of
      vorinostat. Changes in mitochondrial potential, ATP synthesis, and cell cycle
      distribution were determined by Alamar blue reduction, Titer-Glo luminescent
      assays, and flow cytometric, respectively. Protein lysates were isolated from
      vorinostat-exposed cells, and changes in members of Bcl-2 family, cell cycle
      regulatory proteins, and the acetylation status of histone H3 were evaluated by
      Western blotting. Finally, cell lines were pre-exposed to vorinostat for 48 h and
      subsequently exposed to several chemotherapy agents (cisplatin, etoposide, or
      gemcitabine); changes in cell viability were determined by CellTiter-Glo((r))
      luminescence assay (Promega, Fitchburg, WI), and synergistic activity was
      evaluated using the CalcuSyn software. RESULTS: Vorinostat induced dose-dependent
      cell death in RRCL and in primary tumor cells. In addition, in vitro exposure of
      RRCL to vorinostat resulted in an increase in p21 and acetylation of histone H3
      leading to G1 cell cycle arrest. Vorinostat exposure resulted in apoptosis in
      RSCL cell lines but not in RRCL. This finding suggests that in RRCL, vorinostat
      induces cell death by alternative pathways (i.e., irreversible cell cycle
      arrest). Of interest, vorinostat was found to reverse acquired chemotherapy
      resistance in RRCL. CONCLUSIONS: Our data suggest that vorinostat is active in
      RRCL with a known defective apoptotic machinery, it can active alternative cell
      death pathways. Given the multiple pathways affected by HDAC inhibition,
      vorinostat can potentially be used to overcome acquired resistant to chemotherapy
      in aggressive B cell lymphoma.

PMID- 26314220
TI  - Targeted Muscle Reinnervation in the Upper Extremity Amputee: A Technical
      Roadmap.
AB  - Targeted muscle reinnervation (TMR) offers the potential for improved prosthetic
      function by reclaiming the neural control information that is lost as a result of
      upper extremity amputation. In addition to the prosthetic control benefits, TMR
      is a potential treatment for postamputation neuroma pain. Here, we present our
      surgical technique for TMR nerve transfers in transhumeral and shoulder
      disarticulation patients. 

PMID- 26314219
TI  - Epigenetic silencing of Kruppel like factor-3 increases expression of pro
      metastatic miR-182.
AB  - Accumulating evidence indicates that microRNAs (miRs) regulate cancer metastasis.
      We have shown that miR-182 drives sarcoma metastasis in vivo by coordinated
      regulation of multiple genes. Recently, we also demonstrated that in a subset of
      primary sarcomas that metastasize to the lung, miR-182 expression is elevated
      through binding of MyoD1 to the miR-182 promoter. However, it is not known if
      there are also transcription factors that inhibit miR-182 expression. Defining
      negative regulators of miR-182 expression may help explain why some sarcomas do
      not metastasize and may also identify pathways that can modulate miR-182 for
      therapeutic benefit. Here, we use an in silico screen, chromatin
      immunoprecipitation, and luciferase reporter assays to discover that Kruppel like
      factor-3 (Klf-3) is a novel transcriptional repressor of miR-182. Knockdown of
      Klf-3 increases miR-182 expression, and stable overexpression of Klf-3, but not a
      DNA-binding mutant Klf-3, decreases miR-182 levels. Klf-3 expression is
      downregulated in both primary mouse and human metastatic sarcomas, and Klf-3
      levels negatively correlate with miR-182 expression. Interestingly, Klf-3 also
      negatively regulates MyoD1, suggesting an alternative mechanism for Klf-3 to
      repress miR-182 expression in addition to direct binding of the miR-182 promoter.
      Using Methylation Specific PCR (MSP) and pyrosequencing assays, we found that Klf
      3 is epigenetically silenced by DNA hypermethylation both in mouse and human
      sarcoma cells. Finally, we show the DNA methylation inhibitor 5'Azacytidine (Aza)
      restores Klf-3 expression while reducing miR-182 levels. Thus, our findings
      suggest that demethylating agents could potentially be used to modulate miR-182
      levels as a therapeutic strategy. 

PMID- 26314221
TI  - Letter Regarding "The Value of the Tender Muscle Sign in Detecting Motor Recovery
      After Peripheral Nerve Reconstruction".

PMID- 26314222
TI  - Letter Regarding "Olecranon Fractures With Sagittal Splits Treated With Dual
      Fixation".

PMID- 26314223
TI  - A Rare Case of Bilateral Lunotriquetral Coalition and Bilateral Scaphoid
      Nonunion.

PMID- 26314224
TI  - Organic-Inorganic Nanocomposites via Placing Monodisperse Ferroelectric
      Nanocrystals in Direct and Permanent Contact with Ferroelectric Polymers.
AB  - Organic-inorganic nanocomposites composed of polymers and nanoparticles offer a
      vast design space of potential material properties, depending heavily on the
      properties of these two constituents and their spatial arrangement. The ability
      to place polymers in direct contact with functional nanoparticles via strong
      bonding, that is, stable chemical interaction without the dissociation of surface
      capping polymers, provides a means of preventing nanoparticles from aggregation
      and increasing their dispersibility in nanocomposites, and promises opportunities
      to explore new properties and construction of miniaturized devices. However, this
      is still a challenging issue and has not yet been largely explored. Here, we
      report an unconventional strategy to create in situ organic-inorganic
      nanocomposites comprising monodisperse ferroelectric nanoparticles directly and
      permanently tethered with ferroelectric polymers by capitalizing on rationally
      designed amphiphilic star-like diblock copolymer as nanoreactors. The diameter of
      ferroelectric nanoparticles and the chain length of ferroelectric polymers can be
      precisely tuned. The dielectric and ferroelectric properties of nanocomposites
      containing different sizes of ferroelectric nanoparticles were scrutinized. Such
      bottom-up crafting of intimate organic-inorganic nanocomposites offers new levels
      of tailorability to nanostructured materials and promises new opportunities for
      achieving exquisite control over the surface chemistry and properties of
      nanocomposites with engineered functionality for diverse applications in energy
      conversion and storage, catalysis, electronics, nanotechnology, and
      biotechnology. 

PMID- 26314225
TI  - Cytogenetic profile in 1,921 cases of trisomy 21 syndrome.
AB  - BACKGROUND AND AIMS: Trisomy 21 is the most frequent genetic cause of
      intellectual disability. It is caused by different cytogenetic aberrations: free
      trisomy, Robertsonian translocations, mosaicism, duplication of the critical
      region and other structural rearrangements of chromosome 21. The aim of the study
      was to identify in Mexican trisomy 21 patients who attended Hospital Infantil de
      Mexico Federico Gomez from 1992-2011 the type and frequency of the cytogenetic
      aberration and to evaluate the effect of maternal age. METHODS: A retrospective
      analysis of epidemiological data and karyotype reports were carried out; type and
      frequency of the cytogenetic variants were determined. RESULTS: We identified
      2,018 cases referred with a clinical diagnosis of trisomy 21. In 1,921 analyses
      (95.2%) a cytogenetic variant of trisomy 21 was identified: free trisomy 21 in
      1,787 cases (93.02%), four cases (0.21%) had an additional non-contributory
      aberration; Robertsonian translocations in 92 cases (4.79%); mosaicism in 31
      cases (1.61%) and seven cases (0.36%) had other chromosomal abnormalities, five
      (0.26%) had other contributory structural rearrangements and two corresponded to
      double aneuploidies (0.10%). Gender distribution was 1,048 (54.56%) males and 873
      (45.44%) females. A maternal age effect was observed in patients with free
      trisomy 21 with mothers >36 years of age. CONCLUSION: The present work reports
      the experience of a Mexican referral center regarding the karyotype diagnosis of
      patients with trisomy 21 and is one of the most extensive studies published so
      far. Percentages of the cytogenetic abnormalities present in our population
      reflect the ones previously reported for these cytogenetic alterations worldwide.

PMID- 26314226
TI  - Assessment of cardiac functions in children with sickle cell anemia: doppler
      tissue imaging study.
AB  - BACKGROUND AND AIMS: The extent in which sickle cell anemia (SCA) impacts
      myocardial function in children is unclear. Doppler tissue imaging (DTI) was
      introduced as a new non-invasive echocardiographic method for assessment of
      ventricular systolic and diastolic functions. We undertook this study to assess
      subclinical impact of SCA on global myocardial performance in affected children
      using DTI and to correlate it with mean hemoglobin concentration. METHODS: Eighty
      five children with SCA (mean age 11.82 +/- 3.7 years) was included as the study
      group and 55 age- and sex-matched healthy children as the control group.
      Conventional two-dimensional echocardiography was performed in both groups and
      DTI was used to determine right ventricular (RV) and left ventricular (LV) Tei
      indexes. Mean Hb concentration was correlated to the cardiac functions of SCA
      children. RESULTS: RV and LV Tei indexes were significantly higher in SCA group
      (mean +/- SD: 0.54 +/- 0.19 vs. 0.27 +/- 0.01, p <0.0001 and 0.47 +/- 0.09 vs.
      0.30 +/- 0.07, p <0.0001, respectively). Also, mean Hb concentration was
      correlated negatively with both LV Tei index (r = -0.611, p <0.0001) and with RV
      Tei index (r = -0.894, p <0.0001). On the contrary, fractional shortening (FS)
      did not correlate with mean Hb concentration (r = -0.044, p = 0.681).
      CONCLUSIONS: DTI technique appears to be more sensitive than conventional
      echocardiography in the early detection of myocardial dysfunction in children
      with SCA. This provides insights into the value of early screening and the
      potential for preventive therapy in children to avert cardiac morbidity and
      mortality in adults with SCA.

PMID- 26314227
TI  - Cystic Brain Metastases Occurring in Anaplastic Lymphoma Kinase Gene Rearranged
      Non-Small-Cell Lung Cancer Patients Receiving Crizotinib.

PMID- 26314229
TI  - Echinococcus granulosus sensu stricto (s.s.) from the critically endangered
      antelope Addax nasomaculatus in Tunisia.
AB  - Echinococcus granulosus sensu lato (s.l.) is a zoonotic disease highly endemic in
      Tunisia. Canids including stray and semi-stray dogs, jackals and foxes are known
      as definitive hosts and a wide range of ungulates have been shown to harbour the
      metacestode hydatid stage and may serve as intermediate hosts. Fertile hydatid
      cysts of Echinococcus equinus and E. granulosus sensu stricto (s.s.) were
      recently molecularly identified for the first time from Tunisian donkeys. E.
      granulosus (s.s.) was also identified from wild boars in Tunisia. Here we report
      the confirmation of hydatid cysts caused by E. granulosus (s.s.) in the
      critically endangered antelope, Addax nasomaculatus in Tunisia. DNA-based
      molecular analysis revealed that A.nasomaculatus was infected with E. granulosus
      (s.s.) which had a 100% identity with the main globally distributed E. granulosus
      (s.s.) (EgTu01) haplotype. Cysts of Taenia hydatigena (n=33) were also observed
      on the liver and in the body cavity. Due to their endangered status and their
      relatively small numbers, it is unlikely that hydatid infection of A.
      nasomaculatus will form a major contribution to the epidemiology and transmission
      of E. granulosus in Tunisia, but infection may result in pathology, morbidity and
      early mortality, and may still play a role in the perpetuation of the parasite in
      wildlife cycles. 

PMID- 26314228
TI  - Cysteine-Mediated Redox Regulation of Cell Signaling in Chondrocytes Stimulated
      With Fibronectin Fragments.
AB  - OBJECTIVE: Oxidative posttranslational modifications of intracellular proteins
      can potentially regulate signaling pathways relevant to cartilage destruction in
      arthritis. In this study, oxidation of cysteine residues to form sulfenic acid (S
      sulfenylation) was examined in osteoarthritic (OA) chondrocytes and investigated
      in normal chondrocytes as a mechanism by which fragments of fibronectin (FN-f)
      stimulate chondrocyte catabolic signaling. METHODS: Chondrocytes isolated from OA
      and normal human articular cartilage were analyzed using analogs of dimedone that
      specifically and irreversibly react with protein S-sulfenylated cysteines. Global
      S-sulfenylation was measured in cell lysates with and without FN-f stimulation by
      immunoblotting and in fixed cells by confocal microscopy. S-sulfenylation in
      specific proteins was identified by mass spectroscopy and confirmed by
      immunoblotting. Src activity was measured in live cells using a fluorescence
      resonance energy transfer biosensor. RESULTS: Proteins in chondrocytes isolated
      from OA cartilage were found to have elevated basal levels of S-sulfenylation
      relative to those of chondrocytes from normal cartilage. Treatment of normal
      chondrocytes with FN-f induced increased levels of S-sulfenylation in multiple
      proteins, including the tyrosine kinase Src. FN-f treatment also increased the
      levels of Src activity. Pretreatment with dimedone to alter S-sulfenylation
      function or with Src kinase inhibitors inhibited FN-f-induced production of
      matrix metalloproteinase 13. CONCLUSION: These results demonstrate for the first
      time the presence of oxidative posttranslational modification of proteins in
      human articular chondrocytes by S-sulfenylation. Due to the ability to regulate
      the activity of a number of cell signaling pathways, including catabolic
      mediators induced by fibronectin fragments, S-sulfenylation may contribute to
      cartilage destruction in OA and warrants further investigation.

PMID- 26314230
TI  - First report of equine Pegivirus in South America, Brazil.
AB  - The human Pegivirus (HPgV, also known as GBV-C virus or hepatitis G virus) is a
      lymphotropic RNA-virus phylogenetically related to the Hepatitis C virus, which
      infects approximately 5% of the world's human population. Recently, two novel,
      presumably hepatotropic, pegiviruses, designated as equine Pegivirus (EPgV) and
      Theiler's Disease Associated Virus (TDAV), were discovered in horses with
      clinical and laboratory evidence of hepatic disease. To verify the occurrence of
      pegiviruses infection in horses from Para State, northern Brazil, serum samples
      from 114 horses located in four cities (Acara, Belem, Dom Eliseu and Ananindeua)
      were submitted for the molecular analysis of EPgV by nested RT-PCR. The results
      of nucleotide sequencing and phylogenetic analysis of EPgV NS3 and NS5B genomic
      regions confirmed one positive sample among 114 tested samples (1/114; 0.8%). No
      evidence of TDAV infection was found, but despite the low prevalence and unknown
      clinical significance among the studied population, these results represent the
      first molecular detection of EPgV in horses in South America. 

PMID- 26314231
TI  - Patients With Fibromyalgia Have Significant Autonomic Symptoms But Modest
      Autonomic Dysfunction.
AB  - BACKGROUND: Research suggests that disordered autonomic function may be one
      contributor to deconditioning reported in fibromyalgia; however, no study to date
      has assessed these variables simultaneously with comprehensive measures.
      OBJECTIVE: To characterize physical fitness and autonomic function with the use
      of clinically validated measures and subjective questionnaires between patients
      with fibromyalgia and healthy controls. DESIGN: Cross-sectional, observational,
      controlled study. SETTING: Community sample of patients with fibromyalgia and
      healthy controls. PARTICIPANTS: Thirty patients with fibromyalgia and 30 pain and
      fatigue-free controls. METHODS: Participants completed a battery of self-report
      questionnaires and physiological measures, including clinically validated
      measures of physical fitness and autonomic function. MAIN OUTCOME MEASUREMENTS:
      Six-Minute Walk Test total distance, maximal oxygen consumption as assessed by
      cardiopulmonary exercise testing, total steps using activity monitor, Composite
      Autonomic Scoring Scale as assessed by Autonomic Reflex Screen, total metabolic
      equivalents per week using the International Physical Activity Questionnaire, and
      self-reported autonomic symptoms via the 31-item Composite Autonomic Symptom
      Score questionnaire. RESULTS: Autonomic function, as assessed by self-report, was
      significantly different between patients and controls (P < .0001); in contrast,
      the only difference between patients and controls on the Autonomic Reflex Screen
      was in the adrenergic domain (P = .022), and these abnormalities were mild. Self
      reported physical activity was not significantly different between patients and
      controls (P = .99), but levels of moderate and vigorous physical activity as
      measured by actigraphy were significantly lower in patients (P = .012 and P =
      .047, respectively). Exercise capacity (6-Minute Walk) was poorer in patients (P
      = .0006), but there was no significant difference in maximal volume of oxygen
      consumption (P = .07). CONCLUSIONS: Patients with fibromyalgia report more severe
      symptoms across all domains, including physical activity and autonomic symptoms,
      compared with controls, but the objective assessments only showed modest
      differences. Our results suggest that patients with widespread subjective
      impairment of function have only modest objective measures of autonomic
      dysfunction. We recommend that the primary treatment goal should be focused on
      restoration of function, which may also ameliorate symptoms.

PMID- 26314232
TI  - Early Predictors of Functional Outcome After Trauma.
AB  - BACKGROUND: Despite the availability of routinely collected trauma data,
      researchers who investigate rehabilitation outcomes, functional evaluation, and
      comparative effectiveness have not incorporated this potentially clinically
      meaningful information in their modeling as predictors or adjustors. OBJECTIVE:
      The purpose of this study was to identify variables from the scene of a traumatic
      accident and from the emergency department that can be used in assessing
      functional outcomes of persons who survive trauma. DESIGN: Prospective study.
      SETTING: Level I academic trauma center. PATIENTS: Persons who sustained and
      survived a spinal cord injury, a traumatic brain injury, or polytrauma. METHODS:
      Trauma and rehabilitation registries were merged by matching the 2 data files for
      each patient by medical record number, and the files were verified by gender and
      date of birth. Analysis consisted of standard descriptive statistics (frequencies
      and averages). A 2-staged linear regression was used to investigate the
      relationship between the demographic, scene, and ED data elements and discharge
      functional outcome. MAIN OUTCOME MEASURE: Discharge Functional Independence
      Measure (FIM). RESULTS: Older patients with government insurance had poorer
      discharge FIM scores compared with patients who had commercial insurance. The
      Injury Severity Score (ISS) and Glasgow Coma Scale score from the scene of the
      accident were significantly associated with the discharge FIM. Persons with a
      lower ISS had significantly higher discharge FIM scores than did persons with a
      higher ISS (P < .001). For every unit change in Glasgow Coma Scale score, FIM
      scores increased by 0.488 points (P = .030). CONCLUSION: The use of routinely
      collected trauma data elements can be useful in assessing the continuum of
      patient care. Incorporating trauma data into research has the potential to
      improve our models of functional outcomes and provide meaningful risk adjustors
      when comparing and evaluating rehabilitation care systems and treatments.

PMID- 26314233
TI  - Repetitive Transcranial Magnetic Stimulation (rTMS) Therapy in Parkinson Disease:
      A Meta-Analysis.
AB  - OBJECTIVE: Several studies have reported repetitive transcranial magnetic
      stimulation (rTMS) therapy as an effective treatment for the control of motor
      symptoms in Parkinson disease. The objective of the study is to quantify the
      overall efficacy of this treatment. TYPES: Systematic review and meta-analysis.
      LITERATURE SURVEY: We reviewed the literature on clinical rTMS trials in
      Parkinson disease since the technique was introduced in 1980. We used the
      following databases: MEDLINE, Web of Science, Cochrane, and CINAHL. METHODOLOGY: 
      PATIENTS AND SETTING: Patients with Parkinson disease who were participating in
      prospective clinical trials that included an active arm and a control arm and
      change in motor scores on Unified Parkinson's Disease Rating Scale as the primary
      outcome. We pooled data from 21 studies that met these criteria. We then analyzed
      separately the effects of low- and high-frequency rTMS on clinical motor
      improvements. SYNTHESIS: The overall pooled mean difference between treatment and
      control groups in the Unified Parkinson's Disease Rating Scale motor score was
      significant (4.0 points, 95% confidence interval, 1.5, 6.7; P = .005). rTMS
      therapy was effective when low-frequency stimulation (<= 1 Hz) was used with a
      pooled mean difference of 3.3 points (95% confidence interval 1.6, 5.0; P =
      .005). There was a trend for significance when high-frequency stimulation (>= 5
      Hz) studies were evaluated with a pooled mean difference of 3.9 points (95%
      confidence interval, -0.7, 8.5; P = .08). rTMS therapy demonstrated benefits at
      short-term follow-up (immediately after a treatment protocol) with a pooled mean
      difference of 3.4 points (95% confidence interval, 0.3, 6.6; P = .03) as well as
      at long-term follow-up (average follow-up 6 weeks) with mean difference of 4.1
      points (95% confidence interval, -0.15, 8.4; P = .05). There were insufficient
      data to statistically analyze the effects of rTMS when we specifically examined
      bradykinesia, gait, and levodopa-induced dyskinesia using quantitative methods.
      CONCLUSION: rTMS therapy in patients with Parkinson disease results in mild-to
      moderate motor improvements and has the potential to be used as an adjunct
      therapy for the treatment of Parkinson disease. Future large, sample studies
      should be designed to isolate the specific clinical features of Parkinson disease
      that respond well to rTMS therapy.

PMID- 26314235
TI  - Growth rate characteristics of Warthin's tumours of the parotid gland.
AB  - The aim of this study was to evaluate growth characteristics of parotid gland
      Warthin's tumours. The medical records of 134 patients who had a cytological or
      histopathological diagnosis of Warthin's tumour between 1997 and 2013, at a
      single tertiary care centre, were reviewed retrospectively. Thirteen of these
      patients underwent observation with 30 serial computed tomography or magnetic
      resonance imaging scans of the head and neck, with 24 Warthin's lesions
      identified. The mean length of time between scans was 882 days, and mean initial
      and final sizes per lesion were 3.9 cm(3) and 5.6 cm(3), respectively. Average
      growth of these lesions was 8% per year (95% confidence interval -27% to 43%;
      range -148% to 460%; median -8%), and was highly variable (standard deviation
      96%). Age over 75 years was associated with slower growth (P=0.03), but gender,
      smoking status, multifocality, bilaterality versus unilaterality, and initial
      size did not correlate with the growth rate. Warthin's tumours appear to have an
      approximate average doubling time of 9 years, but can have a wide range of growth
      rates, with many cases showing a reduction in size. Either conservative
      management or surgical resection could be supported by these data, depending on
      the current size of the tumour, appearance, symptoms, and the age, health, and
      wishes of the patient.

PMID- 26314234
TI  - Lumbar Intradiskal Platelet-Rich Plasma (PRP) Injections: A Prospective, Double
      Blind, Randomized Controlled Study.
AB  - OBJECTIVE: To determine whether single injections of autologous platelet-rich
      plasma (PRP) into symptomatic degenerative intervertebral disks will improve
      participant-reported pain and function. DESIGN: Prospective, double-blind,
      randomized controlled study. SETTING: Outpatient physiatric spine practice.
      PARTICIPANTS: Adults with chronic (>=6 months), moderate-to-severe lumbar
      diskogenic pain that was unresponsive to conservative treatment. METHODS:
      Participants were randomized to receive intradiskal PRP or contrast agent after
      provocative diskography. Data on pain, physical function, and participant
      satisfaction were collected at 1 week, 4 weeks, 8 weeks, 6 months, and 1 year.
      Participants in the control group who did not improve at 8 weeks were offered the
      option to receive PRP and subsequently followed. MAIN OUTCOME MEASURES:
      Functional Rating Index (FRI), Numeric Rating Scale (NRS) for pain, the pain and
      physical function domains of the 36-item Short Form Health Survey, and the
      modified North American Spine Society (NASS) Outcome Questionnaire were used.
      RESULTS: Forty-seven participants (29 in the treatment group, 18 in the control
      group) were analyzed by an independent observer with a 92% follow-up rate. Over 8
      weeks of follow-up, there were statistically significant improvements in
      participants who received intradiskal PRP with regards to pain (NRS Best Pain) (P
      = .02), function (FRI) (P = .03), and patient satisfaction (NASS Outcome
      Questionnaire) (P = .01) compared with controls. No adverse events of disk space
      infection, neurologic injury, or progressive herniation were reported following
      the injection of PRP. CONCLUSION: Participants who received intradiskal PRP
      showed significant improvements in FRI, NRS Best Pain, and NASS patient
      satisfaction scores over 8 weeks compared with controls. Those who received PRP
      maintained significant improvements in FRI scores through at least 1 year of
      follow-up. Although these results are promising, further studies are needed to
      define the subset of participants most likely to respond to biologic intradiskal
      treatment and the ideal cellular characteristics of the intradiskal PRP
      injectate.

PMID- 26314236
TI  - Amniotic Fluid Embolism: Anaphylactic Reactions With Idiosyncratic Adverse
      Response.
AB  - PROBLEM: Amniotic fluid embolism (AFE) is a rare but severe emergency in
      obstetrics. The aim of the present study was to investigate the pathophysiology
      of AFE. METHODS: A search was conducted between 1966 and 2014 through the English
      language literature (online MEDLINE PubMed database) using the keyword amniotic
      fluid embolism combined with anaphylaxis, anaphylactoid, complement activation,
      mast cells, fetal antigens, and idiosyncratic. RESULTS: Amniotic fluid embolism
      is a rare clinical entity but a severe obstetric emergency that can be lethal
      even in previously healthy women in labor or in the early postpartum period.
      There appears to be at least 2 mechanisms. First, adverse reactions in AFE are
      usually unexpected and fetal antigen dose dependent. Given the disastrous entry
      of amniotic fluid into the maternal circulation, they experience a sudden
      cardiopulmonary collapse (mechanical obstruction subtype). Second, anaphylactic
      and anaphylactoid reactions of the remaining AFE are also relatively unexpected
      and fetal antigen dose independent and can occur at the first exposure to
      amniotic fluid components. They are associated with complement activation and
      subsequent postpartum hemorrhage. Cardiac mast cells constitute a central
      pathogenesis of anaphylactic (immunoglobulin E-dependent) and anaphylactoid
      (immunoglobulin E-independent) reactions. CONCLUSIONS: Recent immunologic studies
      provide a new approach to the study of the pathophysiology of AFE.

PMID- 26314237
TI  - Controversies in the Management of Isolated Congenital Atrioventricular Block.
AB  - Congenital atrioventricular block (CAVB) affects approximately 2% of fetuses of
      mothers with anti-Ro or anti-La antibodies, regardless of maternal rheumatologic
      symptoms. Anti-Ro and anti-La antibodies are antinuclear antibodies commonly
      found in autoimmune diseases. Congenital atrioventricular block is associated
      with a relatively high fetal morbidity and mortality, particularly more advanced
      degrees of block. There is significant controversy surrounding surveillance of
      anti-Ro/La-positive pregnancies and treatment of fetuses diagnosed with CAVB.
      Studies of dexamethasone in the treatment of CAVB have yielded conflicting
      results, with most suggesting only a limited potential benefit in first- and
      seconddegree CAVB and in cases complicated by fetal hydrops. Larger prospective
      studies are needed to further evaluate the efficacy of intravenous immunoglobulin
      in the treatment of CAVB and of intravenous immunoglobulin and hydroxychloroquine
      in the prevention of CAVB in fetuses of at-risk mothers. Surveillance and
      treatment regimens should be determined on a case-by-case basis, taking into
      consideration the degree of CAVB, costs, and potential adverse effects of
      treatment. 

PMID- 26314238
TI  - Interventions for Intrauterine Resuscitation in Suspected Fetal Distress During
      Term Labor: A Systematic Review.
AB  - IMPORTANCE: Intrauterine resuscitation techniques during term labor are commonly
      used in daily clinical practice. Evidence, however, to support the beneficial
      effect of intrauterine resuscitation techniques on fetal distress during labor is
      limited and sometimes contradictory. In contrast, some of these interventions may
      even be harmful. OBJECTIVE: To give insight into the current evidence on
      intrauterine resuscitation techniques. In addition, we formulate recommendations
      for current clinical practice and propose directions for further research.
      EVIDENCE ACQUISITION: We systematically searched the electronic PubMed, EMBASE,
      and CENTRAL databases for studies on intrauterine resuscitation for suspected
      fetal distress during term labor until February 2015. Eligible articles and their
      references were independently assessed by 2 authors. Judgment was based on
      methodological quality and study results. RESULTS: Our literature search
      identified 15 studies: 4 studies on amnioinfusion, 1 study on maternal
      hyperoxygenation, 1 study on maternal repositioning, 1 study on intravenous fluid
      administration, and 8 studies on tocolysis. Of these 15 research papers, 3
      described a randomized controlled trial; all other studies were observational
      reports or case reports. CONCLUSIONS AND RELEVANCE: Little robust evidence to
      promote a specific intrauterine resuscitation technique is available. Based on
      our literature search, we support the use of tocolysis and maternal repositioning
      for fetal distress. We believe the effect of amnioinfusion and maternal
      hyperoxygenation should be further investigated in properly designed randomized
      controlled trials to make up the balance between beneficial and potential
      hazardous effects.

PMID- 26314239
TI  - Morcellation of occult uterine malignancies: an Australian single institution
      retrospective study.
AB  - INTRODUCTION: Morcellation for tissue extraction during laparoscopic hysterectomy
      or myomectomy has recently been questioned because of the potential to spread
      occult uterine cancers. The Australian Therapeutic Goods Administration (TGA)
      issued a safety advisory in August 2014, estimating the risk of occult malignancy
      in the Australian population to be one in 1000 or lower, based on estimates from
      overseas studies in the absence of any local data. AIMS: The aim of this study
      was to determine the incidence of occult uterine malignancies in morcellated
      surgical specimens at St John of God Hospital in Perth, Western Australia.
      MATERIALS AND METHODS: All women who had a hysterectomy or myomectomy with
      morcellation of the surgical specimen for presumed benign uterine fibroids at our
      institution from 01 November 2009 to 12 March 2015 were identified and stratified
      into benign disease, uncertain malignant potential and malignant. RESULTS: Seven
      hundred and thirty-four women were included, and three malignancies were
      identified: two cases with leiomyosarcoma (LMS) and another with an endometrioid
      endometrial adenocarcinoma (EAC). One case of serous tubal in situ carcinoma
      (STIC) and two cases of benign metastasising leiomyoma/leiomyomatosis were also
      identified. The overall risk of malignancy in a morcellated surgical specimen was
      0.41% (three in 734). The risk of morcellating an incidental uterine malignancy
      was 0.27% for LMS and 0.14% for EAC. All three incidental malignancies were
      diagnosed in premenopausal women. CONCLUSIONS: The risk of unintended
      morcellation of uterine malignancy in our study is higher than that estimated by
      the Australian TGA and highlights the urgent need for further studies in
      Australia.

PMID- 26314240
TI  - Proteomic analysis of plasma from rats following total parenteral nutrition
      induced liver injury.
AB  - Total parenteral nutrition (TPN) is provided as the primary nitrogen source to
      manage patients with intestinal failure who were not able to sustain themselves
      on enteral feeds. The most common complication of long-term TPN use is hepatitis.
      A proteomic approach was used to identify proteins that are differentially
      expressed in the plasma of rats following TPN-related acute liver injury. Six
      male rats were randomly assigned to either the saline infusion control group or
      the TPN infusion group. Our results demonstrate that TPN infusion in rats
      resulted in hepatic dysfunction and hepatocyte apoptosis. Five proteins that were
      differentially expressed between TPN infusion and normal rats were determined and
      validated in vivo. Fascinatingly, the proteomic differential displays,
      downregulated proteins included peroxiredoxin 2 (PRDX2), alpha-1-antiproteinase
      (A1AT), and fibrinogen gamma chain (FIBG), which were involved in oxidative
      stress, inflammatory respondence and cells apoptosis. After TPN infusion, two
      protein spots showed increased expression, namely, the glucagon receptor (GLR)
      protein and apolipoprotein A-1 (APOA1), which may mediate the effects of TPN
      administration on glycogen and lipid metabolism. In this study, proteomic
      analysis suggested TPN-related acute liver injury could be involved in limiting
      cellular protection mechanisms against oxidative stress-induced apoptosis. On the
      basis of the results, we also give molecular evidences replying TPN-related
      hepatitis. 

PMID- 26314241
TI  - Comparison of duplicate portion and 24 h recall as reference methods for
      validating a FFQ using urinary markers as the estimate of true intake.
AB  - As FFQ are subject to measurement error, associations between self-reported
      intake by FFQ and outcome measures should be adjusted by correction factors
      obtained from a validation study. Whether the correction is adequate depends on
      the characteristics of the reference method used in the validation study.
      Preferably, reference methods should (1) be unbiased and (2) have uncorrelated
      errors with those in the FFQ. The aim of the present study was to assess the
      validity of the duplicate portion (DP) technique as a reference method and
      compare its validity with that of a commonly used reference method, the 24 h
      recall (24hR), for protein, K and Na using urinary markers as the unbiased
      reference method. For 198 subjects, two DP, two FFQ, two urinary biomarkers and
      between one and fifteen 24hR (web based and/or telephone based) were collected
      within 1.5 years. Multivariate measurement error models were used to estimate
      bias, error correlations between FFQ and DP or 24hR, and attenuation factors of
      these methods. The DP was less influenced by proportional scaling bias (0.58 for
      protein, 0.72 for K and 0.52 for Na), and correlated errors between DP and FFQ
      were lowest (protein 0.28, K 0.17 and Na 0.19) compared with the 24hR.
      Attenuation factors (protein 0.74, K 0.54 and Na 0.43) also indicated that the DP
      performed better than the 24hR. Therefore, the DP is probably the best available
      reference method for FFQ validation for nutrients that currently have no
      generally accepted recovery biomarker. 

PMID- 26314242
TI  - Osmoporin OmpC forms a complex with MlaA to maintain outer membrane lipid
      asymmetry in Escherichia coli.
AB  - Gram-negative bacteria can survive in harsh environments in part because the
      asymmetric outer membrane (OM) hinders the entry of toxic compounds. Lipid
      asymmetry is established by having phospholipids (PLs) confined to the inner
      leaflet of the membrane and lipopolysaccharides (LPS) to the outer leaflet.
      Perturbation of OM lipid asymmetry, characterized by PL accumulation in the outer
      leaflet, disrupts proper LPS packing and increases membrane permeability. The
      multi-component Mla system prevents PL accumulation in the outer leaflet of the
      OM via an unknown mechanism. Here, we demonstrate that in Escherichia coli, the
      Mla system maintains OM lipid asymmetry with the help of osmoporin OmpC. We show
      that the OM lipoprotein MlaA interacts specifically with OmpC and OmpF. This
      interaction is sufficient to localize MlaA lacking its lipid anchor to the OM.
      Removing OmpC, but not OmpF, causes accumulation of PLs in the outer leaflet of
      the OM in stationary phase, as was previously observed for MlaA. We establish
      that OmpC is an additional component of the Mla system; the OmpC-MlaA complex may
      function to remove PLs directly from the outer leaflet to maintain OM lipid
      asymmetry. Our work reveals a novel function for the general diffusion channel
      OmpC in lipid transport. 

PMID- 26314243
TI  - Co-Amorphous Combination of Nateglinide-Metformin Hydrochloride for Dissolution
      Enhancement.
AB  - The aim of the present work was to prepare a co-amorphous mixture (COAM) of
      Nateglinide and Metformin hydrochloride to enhance the dissolution rate of poorly
      soluble Nateglinide. Nateglinide (120 mg) and Metformin hydrochloride (500 mg)
      COAM, as a dose ratio, were prepared by ball-milling technique. COAMs were
      characterized for saturation solubility, amorphism and physicochemical
      interactions (X-ray powder diffraction (XRPD), differential scanning calorimetry
      (DSC), Fourier transform infrared spectroscopy (FTIR)), SEM, in vitro
      dissolution, and stability studies. Solubility studies revealed a sevenfold rise
      in solubility of Nateglinide from 0.061 to 0.423 mg/ml in dose ratio of COAM.
      Solid-state characterization of COAM suggested amorphization of Nateglinide after
      6 h of ball milling. XRPD and DSC studies confirmed amorphism in Nateglinide,
      whereas FTIR elucidated hydrogen interactions (proton exchange between
      Nateglinide and Metformin hydrochloride). Interestingly, due to low energy of
      fusion, Nateglinide was completely amorphized and stabilized by Metformin
      hydrochloride. Consequently, in vitro drug release showed significant increase in
      dissolution of Nateglinide in COAM, irrespective of dissolution medium. However,
      little change was observed in the solubility and dissolution profile of Metformin
      hydrochloride, revealing small change in its crystallinity. Stability data
      indicated no traces of devitrification in XRPD of stability sample of COAM, and %
      drug release remained unaffected at accelerated storage conditions. Amorphism of
      Nateglinide, proton exchange with Metformin hydrochloride, and stabilization of
      its amorphous form have been noted in ball-milled COAM of Nateglinide-Metformin
      hydrochloride, revealing enhanced dissolution of Nateglinide. Thus, COAM of
      Nateglinide-Metformin hydrochloride system is a promising approach for
      combination therapy in diabetic patients. 

PMID- 26314244
TI  - Effect of Antiadherents on the Physical and Drug Release Properties of Acrylic
      Polymeric Films.
AB  - Antiadherents are used to decrease tackiness of a polymer coating during both
      processing and subsequent storage. Despite being a common excipient in coating
      formulae, antiadherents may affect mechanical properties of the coating film as
      well as drug release from film-coated tablets, but how could addition of
      antiadherents affect these properties and to what extent and is there a relation
      between the physical characteristics of the tablet coat and the drug release
      mechanisms? The aim of this study was to evaluate physical characteristics of
      films containing different amounts of the antiadherents talc, glyceryl
      monostearate, and PlasACRYL(TM) T20. Eudragit RL30D and Eudragit RS30D as
      sustained release polymers and Eudragit FS30D as a delayed release material were
      used. Polymer films were characterized by tensile testing, differential scanning
      calorimetry (DSC), microscopic examination, and water content as calculated from
      loss on drying. The effect of antiadherents on in vitro drug release for the
      model acetylsalicylic acid tablets coated with Eudragit FS30D was also
      determined. Increasing talc concentration was found to decrease the ability of
      the polymer films to resist mechanical stress. In contrast, glyceryl monostearate
      (GMS) and PlasACRYL produced more elastic films. Talc at concentrations higher
      than 25% caused negative effects, which make 25% concentration recommended to be
      used with acrylic polymers. All antiadherents delayed the drug release at all
      coating levels; hence, different tailoring of drug release may be achieved by
      adjusting antiadherent concentration with coating level. 

PMID- 26314245
TI  - Novel Strategy to Fabricate Floating Drug Delivery System Based on Sublimation
      Technique.
AB  - The present study aims to develop floating drug delivery system by sublimation of
      ammonium carbonate (AMC). The core tablets contain a model drug,
      hydrochlorothiazide, and various levels (i.e., 0-50% w/w) of AMC. The tablets
      were then coated with different amounts of the polyacrylate polymers (i.e.,
      Eudragit(r) RL100, Eudragit(r) RS100, and the mixture of Eudragit(r) RL100 and
      Eudragit(r) RS100 at 1:1 ratio). The coated tablets were kept at ambient
      temperature (25 degrees C) or cured at 70 degrees C for 12 h before further
      investigation. The floating and drug release behaviors of the tablets were
      performed in simulated gastric fluid USP without pepsin at 37 degrees C. The
      results showed that high amount of AMC induced the floating of the tablets. The
      coated tablets containing 40 and 50% AMC floated longer than 8 h with a time-to
      float of about 3 min. The sublimation of AMC from the core tablets decreased the
      density of system, causing floating of the tablets. The tablets coated with
      Eudragit(r) RL100 floated at a faster rate than those of Eudragit(r) RS100. Even
      the coating level of polymer did not influence the time-to-float and floating
      time of coated tablets containing the same amount of AMC, the drug release from
      the tablets coated with higher coating level of polymer showed slower drug
      release. The results suggested that the sublimation technique using AMC is
      promising for the development of floating drug delivery system. 

PMID- 26314246
TI  - In Vitro Anti-inflammatory and Antimicrobial Activities of Azithromycin After
      Loaded in Chitosan- and Tween 20-Based Oil-in-Water Macroemulsion for Acne
      Management.
AB  - The objectives of the current investigation are (1) to prepare and characterize
      (particle size, surface charge (potential zeta), surface morphology by
      transmission electron microscopy, drug content, and drug release) the
      azithromycin (AZM, 100 mg)-loaded oil-in-water (o/w) macroemulsion, (2) to assess
      the toxicity of macroemulsion with or without AZM using RBC lysis test in
      comparison with AZM in phosphate buffer solution of pH 7.4, (3) to compare the in
      vitro antimicrobial activity (in Escherichia coli using zone inhibition assay) of
      AZM-loaded macroemulsion with its aqueous solution, and (4) to assess the in
      vitro anti-inflammatory effect (using egg albumin denaturation bioassay) of the
      AZM-loaded macroemulsion in comparison with diclofenac sodium in phosphate buffer
      solution of pH 7.4. The AZM-loaded macroemulsion possessed the dispersed oil
      droplets with a mean diameter value of 52.40 +/- 1.55 MUm. A reversal in the zeta
      potential value from negative (-2.16 +/- 0.75 mV) to positive (+6.52 +/- 0.96 mV)
      was noticed when AZM was added into the macroemulsion. At a 1:5 dilution ratio,
      2.06 +/- 0.03 mg of drug was released from macroemulsion followed by 1.01 +/-
      0.01 and 0.25 +/- 0.08 mg, respectively, for 1:10 and 1:40 dilution ratios.
      Antimicrobial activity maintenance and significant reduction of RBC lysis
      property were noticed for AZM after loaded in the macroemulsion. However, an
      increment in the absorbance values for emulsion-treated samples in comparison to
      the control samples was noticed in the anti-inflammatory test. This speculates
      the potential of the AZM-loaded emulsion to manage inflammatory conditions
      produced at Acne vulgaris. 

PMID- 26314247
TI  - A facile and low-cost micro fabrication material: flash foam.
AB  - Although many microfabrication methods have been reported, the preliminary
      replication templates used in most microfabrication still depend on the expensive
      and long-period photolithography. This paper explores an alternative replication
      templates based on a daily used material, flash foam (FF), and proposes a facile
      microfabrication method, flash foam stamp lithography (FFSL). When FF is exposed
      with a desired pattern mask, the negative of the pattern is transferred to its
      surface and micro structures are formed due to the shrinkage of the exposed area.
      As FF is commonly used in personal stamps, FFSL is very simple and cost
      effective. In this paper, we demonstrated that FF is a good and low-cost template
      for many micro fabrication methods, such as micro casting and soft lithography.
      Thus, designing and fabricating micro structures at personal office immediately
      become possible with FFSL. Furthermore, we demonstrated that multi-scale micro
      structures can be easily fabricated by double exposure with FFSL. Skin textures
      is used as another case to demonstrate that FFSL can fabricate structures with
      different depth in a single exposure. As a result, FF shows a promising future in
      biology, and analytical chemistry, such as rapid fabrication of point of care
      diagnostics and microfluidic analytical devices with low cost. 

PMID- 26314248
TI  - Nursing teams caring for hospitalised older adults.
AB  - AIMS AND OBJECTIVES: To offer an explanation of how registered nurses' are
      providing care to hospitalised older adults in nursing teams comprised of a
      variety of roles and educational levels. BACKGROUND: Around the globe economic
      pressures, nursing shortages and increased patient acuity have resulted in tasks
      being shifted to healthcare workers with less education and fewer qualifications
      than registered nurses. In acute care hospitals, this often means reducing the
      number of registered nurses and adding licensed practical nurses and care aides
      (also referred to as unregulated healthcare workers) to the nursing care team.
      The implications of these changes are not well understood especially in the
      context of hospitalised older adults, who are complex and the most common care
      recipients. DESIGN: Thematic analysis of data that were collected in a previous
      grounded theory study to provide an opportunity in-depth analysis of how nurses
      provided care to hospitalised older adults within nursing teams. METHODS: Data
      collected in western Canada on two hospital units in two different health
      authorities were analysed in relation to how nursing teams provide care. Hand
      coding and thematic analysis were employed. RESULTS: The themes of scrutinised
      skill mix and working together highlighted how the established nursing value of
      reciprocity is challenging to enact in teams with a variety of scopes of
      practice. The value of reciprocity both aided and hindered the nursing team in
      engaging in team behaviours to effectively manage patient care. CONCLUSION:
      Educators and leaders could assist the nursing care team in re-thinking how they
      engage in teamwork by providing education about roles and communication
      techniques to support teams and ultimately improve nursing care. RELEVANCE TO
      CLINICAL PRACTICE: The value of reciprocity within nursing teams needs to be re
      examined within the context of team members with varying abilities to reciprocate
      in kind.

PMID- 26314249
TI  - Imaging the Patient With Migraine: A Question Answered.

PMID- 26314250
TI  - Clinical Practice Patterns Suggest Female Patients Prefer Female Endoscopists.

PMID- 26314251
TI  - Assessing structural correlations and heterogeneity length scales in functional
      porous polymers from physical reconstructions.
AB  - A general, model-free, quantitative approach to the key morphological properties
      of a porous polymer monolith is presented. After 3D reconstruction, image-based
      analysis delivers detailed spatial and spatially correlated information on the
      structural heterogeneities in the void space and the polymer skeleton. Identified
      heterogeneities, which limit the monolith's performance in targeted applications,
      are traced back to the preparation process. 

PMID- 26314252
TI  - The expression of RNA helicase DDX5 is transcriptionally upregulated by
      calcitriol through a vitamin D response element in the proximal promoter in SiHa
      cervical cells.
AB  - The DEAD box RNA helicase DDX5 is a multifunctional protein involved in the
      regulatory events of gene expression. Herein, we presented evidence indicating
      that DDX5 is transcriptionally upregulated by calcitriol, the hormonal form of
      vitamin D3. In silico analysis revealed the presence of two putative vitamin D
      response elements (VDREs) in the DDX5 promoter region. Using luciferase reporter
      assays, we demonstrated that the DDX5 promoter containing these putative VDREs
      significantly increased the luciferase activity in vitamin D receptor (VDR)
      positive SiHa cells upon calcitriol treatment. Electrophoretic mobility shift
      assays showed the ability of VDR and retinoid X receptor to interact only with
      the most proximal VDRE, while chromatin immunoprecipitation analysis confirmed
      the occupancy of this VDRE by the VDR. Finally, we demonstrated that calcitriol
      significantly increased both DDX5 mRNA and protein in SiHa cells. In summary,
      this study shows that DDX5 gene is transcriptionally upregulated by calcitriol
      through a VDRE located in its proximal promoter. Given the importance of DDX5 as
      a master regulator of differentiation programs, our study suggests that the pro
      differentiating properties of calcitriol may be related with the induction of
      DDX5. 

PMID- 26314253
TI  - The role of FGF2 in migration and tubulogenesis of endothelial progenitor cells
      in relation to pro-angiogenic growth factor production.
AB  - In recent years, special attention has been paid to finding new pro-angiogenic
      factors which could be used in gene therapy of vascular diseases such as critical
      limb ischaemia (CLI). Angiogenesis, the formation of new blood vessels, is a
      complex process dependent on different cytokines, matrix proteins, growth factors
      and other pro- or anti-angiogenic stimuli. Numerous lines of evidence suggest
      that key mediators of angiogenesis, vascular endothelial growth factor (VEGF) and
      hepatocyte growth factor (HGF) together with fibroblast growth factor2 (FGF2) are
      involved in regulation of the normal and pathological process of angiogenesis.
      However, less information is available on the complex interactions between these
      and other angiogenic factors. The aim of this study was to characterise the
      effect of fibroblast growth factor2 on biological properties of human endothelial
      progenitor cells with respect to the expression level of other regulatory
      cytokines. Ectopic expression of FGF2 in EP cells stimulates their pro-angiogenic
      behaviour, leading to increased proliferation, migration and tube formation
      abilities. Moreover, we show that the expression profile of VEGF and other pro
      angiogenic cytokines, such as HGF, MCP2, and interleukins, is affected
      differently by FGF2 in EPC. In conclusion, we provide evidence that FGF2 directly
      affects not only the biological properties of EP cells but also the expression
      pattern and secretion of numerous chemocytokines. Our results suggest that FGF2
      could be applied in therapeutic approaches for CLI and other ischaemic diseases
      of the vascular system in vivo.

PMID- 26314254
TI  - Cardiolipin composition correlates with prostate cancer cell proliferation.
AB  - Prostate cancer (PC) is the second most diagnosed cancer in men. It has been
      recognized that diet can play a crucial role in PC genesis and progression. In
      this context, free fatty acids are considered as modulators of cell
      proliferation. Recently, a relationship between the composition of the
      mitochondrial phospholipid cardiolipin (CL) and cell proliferation has been
      discussed. The aim of this study was to analyse the interrelationship between CL
      composition and the proliferation of prostate cells by exposing PC-3 tumour cells
      to different fatty acids and by analysing the CL composition in prostate tissue
      from PC patients after prostatectomy. Among the applied fatty acids, palmitic
      acid was found to stimulate proliferation of PC-3 cells, whereas oleic acid (OA)
      had an inhibiting effect. The lipidomic analysis of CL revealed that fatty acids
      supplied to PC-3 cells were incorporated into CL molecules. Further, the CL
      content of palmitoleic acid (C16:1) exclusively correlated with the proliferation
      of PC-3 cells. The CL composition significantly differed between tumour and
      normal prostate tissue from PC patients. In five out of six patients, the CL
      content of palmitoleic acid was higher in tumour prostate tissue in comparison to
      normal prostate tissue. Our data illustrate that the composition of CL can be
      easily modified by the fatty acid environment of cells. OA was most effective in
      decreasing the amount of palmitoleic acid within the CL molecules and
      deceleration of PC-3 cell proliferation. In conclusion, a diet rich in OA might
      be beneficial in protecting from rapid proliferation of PC cells. 

PMID- 26314256
TI  - Efficient swimming of an assembly of rigid spheres at low Reynolds number.
AB  - The swimming of an assembly of rigid spheres immersed in a viscous fluid of
      infinite extent is studied in low-Reynolds-number hydrodynamics. The
      instantaneous swimming velocity and rate of dissipation are expressed in terms of
      the time-dependent displacements of sphere centers about their collective motion.
      For small-amplitude swimming with periodically oscillating displacements,
      optimization of the mean swimming speed at given mean power leads to an
      eigenvalue problem involving a velocity matrix and a power matrix. The
      corresponding optimal stroke permits generalization to large-amplitude motion in
      a model of spheres with harmonic interactions and corresponding actuating forces.
      The method allows straightforward calculation of the swimming performance of
      structures modeled as assemblies of interacting rigid spheres. A model of three
      collinear spheres with motion along the common axis is studied as an example. 

PMID- 26314255
TI  - Effect of ultraviolet A-induced crosslinking on dentin collagen matrix.
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of using UVA-induced
      crosslinking with or without riboflavin as photosensitizers on degradation of
      dentin matrix by dentin proteases. METHODS: Demineralized dentin specimens
      (0.4*3*6 mm(3), n=10/group) were subjected to: (RP1), 0.1% riboflavin-5
      phosphate/UVA for 1 min; (RP5), 0.1% riboflavin-5 phosphate/UVA for 5 min; (R1),
      0.1% riboflavin/UVA for 1 min; (R5), 0.1% riboflavin-UVA for 5 min; (UV1), UVA
      for 1 min; (UV5), UVA for 5 min. Specimens were incubated in 1 mL zinc and
      calcium containing media for 1 day and 1 week. An untreated group served as
      control (CM). After incubation, the loss of dry mass of samples was measured and
      aliquots of media were analyzed for the release of C-terminal fragment
      telopeptide (ICTP vs. CTX) of collagen to evaluate for cathepsin K (CA-K) and
      total matrix metalloproteinase (MMP)-mediated degradation. Data were analyzed
      using repeated measures ANOVA at alpha=0.05. RESULTS: Although UVA radiation
      alone reduced dentin degradation, UVA-activated riboflavin or riboflavin-5
      phosphate inhibited MMP and CA-K activities more than UVA alone. The effects of
      crosslinking were more pronounced in 7-day samples; only with CA-K were the
      effects of crosslinking with or without photosensitizer significantly different
      from controls in 1-day samples. SIGNIFICANCE: The use of bioactive forms (RP) or
      longer treatment time did not result with better effect. The use of UVA
      crosslinking reduces dentin matrix degradation, especially with photosensitizers.

PMID- 26314257
TI  - Mesoscopic simulation of single DNA dynamics in rotational flows.
AB  - In this numerical study, the transport and dynamics of an isolated DNA in
      rotational flow generated in a microchannel have been investigated using
      dissipative particle dynamics. Often, inertial flow through microchannels with a
      sudden change in surface structure facilitates a re-circulation or vortex region.
      The conformation and mobility of the bio-polymer under the influence of such
      rotating fluid inside a square cavity of the microchannel is analyzed. The
      flexible polymer chain is found to migrate towards the rotating region and
      follows the vortex streamline. The orientation, size and tumbling period of
      polymer strands are affected by the strength of the microvortex. At elevated flow
      rates, the macromolecule prefers to remain inside the vortex and a hydrodynamic
      trap is formed. Moreover, residence time of the single molecule in the
      microcavity is significantly influenced by the chain length and flow strength.
      Further, it has been demonstrated that, such entrapment duration can be
      strategically altered by modifying the hydrophobicity of the microchannel. 

PMID- 26314258
TI  - Rigorous study of molecular dynamics of a single dsDNA confined in a nanochannel:
      Introduction of a critical mobility behaviour.
AB  - The essential and effective characteristics of a double-stranded DNA (dsDNA)
      confined in a nanochannel is revisited by employing the rigorous full numerical
      approach of Molecular Dynamics (MD). The deformation of dsDNA and wall
      biomolecule interaction which is critical in highly confined regime has been
      precisely imposed in numerical simulations. The numerical approach has been
      justified against available theoretical outcomes. A new and general expression
      for DNA electrophoretic mobility versus DNA length is extracted from numerical
      simulation which is out of reach of experimental methods due to practical
      shortcomings. The newly derived expression suggests an essential correction in
      the previously proposed expression for the critical case of small DNA molecules
      and reveals an astonishingly unbeknown trend of small DNA's mobility. Sub
      molecular phenomenon of dsDNA melting under the condition of large external force
      is also studied. Assuming strong electric field exertion, the MD approach aptly
      demonstrates the elaborate melting phenomenon for dsDNA in sub-molecular scale. 

PMID- 26314259
TI  - Minimal model for transient swimming in a liquid crystal.
AB  - When a microorganism begins swimming from rest in a Newtonian fluid such as
      water, it rapidly attains its steady-state swimming speed since changes in the
      velocity field spread quickly when the Reynolds number is small. However,
      swimming microorganisms are commonly found or studied in complex fluids. Because
      these fluids have long relaxation times, the time to attain the steady-state
      swimming speed can also be long. In this article we study the swimming startup
      problem in the simplest liquid crystalline fluid: a two-dimensional hexatic
      liquid crystal film. We study the dependence of startup time on anchoring
      strength and Ericksen number, which is the ratio of viscous to elastic stresses.
      For strong anchoring, the fluid flow starts up immediately but the liquid crystal
      field and swimming velocity attain their sinusoidal steady-state values after a
      time proportional to the relaxation time of the liquid crystal. When the Ericksen
      number is high, the behavior is the same as in the strong-anchoring case for any
      anchoring strength. We also find that the startup time increases with the ratio
      of the rotational viscosity to the shear viscosity, and then ultimately saturates
      once the rotational viscosity is much greater than the shear viscosity. 

PMID- 26314260
TI  - Self-phoretic active particles interacting by diffusiophoresis: A numerical study
      of the collapsed state and dynamic clustering.
AB  - Self-phoretic active colloids move and orient along self-generated chemical
      gradients by diffusiophoresis, a mechanism reminiscent of bacterial chemotaxis.
      In combination with the activity of the colloids, this creates effective
      repulsive and attractive interactions between particles depending on the sign of
      the translational and rotational diffusiophoretic parameters. A delicate balance
      of these interactions causes dynamic clustering and for overall strong effective
      attraction the particles collapse to one single cluster. Using Langevin dynamics
      simulations, we extend the state diagram of our earlier work (Phys. Rev. Lett.
      112, 238303 (2014)) to regions with translational phoretic repulsion. With
      increasing repulsive strength, the collapsed cluster first starts to fluctuate
      strongly, then oscillates between a compact form and a colloidal cloud, and
      ultimately the colloidal cloud becomes static. The oscillations disappear if the
      phoretic interactions within compact clusters are not screened. We also study
      dynamic clustering at larger area fractions by exploiting cluster size
      distributions and mean cluster sizes. In particular, we identify the dynamic
      clustering 2 state as a signature of phoretic interactions. We analyze fusion and
      fission rate functions to quantify the kinetics of cluster formation and identify
      them as local signatures of phoretic interactions, since they can be measured on
      single clusters. 

PMID- 26314261
TI  - The Modified VFT law of glass former materials under pressure: Part II: Relation
      with the equation of state.
AB  - The dynamical properties of glass formers (GFs) as a function of P, V, and T are
      reanalyzed in relation with the equations of state (EOS) proposed recently (Eur.
      Phys. J. E 37, 113 (2014)). The relaxation times tau of the cooperative non
      Arrhenius alpha process and the individual Arrhenius beta process are coupled via
      the Kohlrausch exponent n S(T, P). In the model n S is the sigmoidal logistic
      function depending on T (and P, and the alpha relaxation time tau alpha of GFs
      above T g verifies the pressure-modified VFT law: log tau alpha ~ E beta /nsRT,
      which can be put into a form with separated variables: log tau alpha ~ f(T)g(P).
      From the variation of n S and tau alpha with T and P the Vogel temperature T 0
      (tau alpha -> ?, n S = 0) and the crossover temperature (also called the merging
      or splitting temperature) T B (tau alpha ~ tau beta, n S ~ 1) are determined. The
      proposed sm-VFT equation fits with excellent accuracy the experimental data of
      fragile and strong GFs under pressure. The properties generally observed in
      organic mineral and metallic GFs are explained: a) The Vogel temperature is
      independent of P (as suggested by the EOS properties), the crossover is pressure
      dependent. b) In crystallizable GFs the T B (P) and Clapeyron curves T m(P)
      coincide. c) The alpha and beta processes have the same ratio of the activation
      energies and volume, E*/V* (T- and P-independent), the compensation law is
      observed, this ratio depends on the anharmonicity Slater-Gruneisen parameter and
      on the critical pressure P* deduced from the EOS. d) The properties of the Fan
      Structure of the Tangents (FST) to the isotherms and isobars curves log tau
      versus P and T and to the isochrones curves P(T). e) The scaling law log tau =
      f(V (Lambda) ) and the relation between Gamma and gamma. We conclude that these
      properties should be studied in detail in GFs submitted to negative pressures. 

PMID- 26314263
TI  - Inhibition of CXCL12-mediated chemotaxis of Jurkat cells by direct
      immunotoxicants.
AB  - Directional migration of cells to specific locations is required in tissue
      development, wound healing, and immune responses. Immune cell migration plays a
      crucial role in both innate and adaptive immunity. Chemokines are small pro
      inflammatory chemoattractants that control the migration of leukocytes. In
      addition, they are also involved in other immune processes such as lymphocyte
      development and immune pathology. In a previous toxicogenomics study using the
      Jurkat T cell line, we have shown that the model immunotoxicant TBTO inhibited
      chemotaxis toward the chemokine CXCL12. In the present work, we aimed at
      assessing a novel approach to detecting chemicals that affect the process of cell
      migration. For this, we first evaluated the effects of 31 chemicals on mRNA
      expression of genes that are known to be related to cell migration. With this
      analysis, seven immunotoxicants were identified as potential chemotaxis
      modulators, of which five (CoCl2 80 uM, MeHg 1 uM, ochratoxin A 10 uM, S9-treated
      ochratoxin A 10 uM, and TBTO 100 nM) were confirmed as chemotaxis inhibitor in an
      in vitro trans-well chemotaxis assay using the chemokine CXCL12. The
      transcriptome data of the five compounds together with previously obtained
      protein phosphorylation profiles for two out of five compounds (i.e., ochratoxin
      A and TBTO) revealed that the mechanisms behind the chemotaxis inhibition are
      different for these immunotoxicants. Moreover, the mTOR inhibitor rapamycin had
      no effect on the chemotaxis of Jurkat cells, indicating that the mTOR pathway is
      not involved in CXCL12-mediated chemotaxis of Jurkat cells, which is opposite to
      the findings on human primary T cells (Munk et al. in PLoS One 6(9):e24667,
      2011). Thus, the results obtained from the chemotaxis assay conducted with Jurkat
      cells might not fully represent the results obtained with human primary T cells.
      Despite this difference, the present study indicated that some compounds may
      exert their immunotoxic effects through inhibition of CXCL12-mediated chemotaxis.

PMID- 26314262
TI  - Toxicology: a discipline in need of academic anchoring--the point of view of the
      German Society of Toxicology.
AB  - The paper describes the importance of toxicology as a discipline, its past
      achievements, current scientific challenges, and future development.
      Toxicological expertise is instrumental in the reduction of human health risks
      arising from chemicals and drugs. Toxicological assessment is needed to evaluate
      evidence and arguments, whether or not there is a scientific base for concern.
      The immense success already achieved by toxicological work is exemplified by
      reduced pollution of air, soil, water, and safer working places. Predominantly
      predictive toxicological testing is derived from the findings to assess risks to
      humans and the environment. Assessment of the adversity of molecular effects
      (including epigenetic effects), the effects of mixtures, and integration of
      exposure and biokinetics into in vitro testing are emerging challenges for
      toxicology. Toxicology is a translational science with its base in fundamental
      science. Academic institutions play an essential part by providing scientific
      innovation and education of young scientists. 

PMID- 26314264
TI  - Developmental exposure to T-2 toxin reversibly affects postnatal hippocampal
      neurogenesis and reduces neural stem cells and progenitor cells in mice.
AB  - To determine the developmental exposure effects of T-2 toxin on postnatal
      hippocampal neurogenesis, pregnant ICR mice were provided a diet containing T-2
      toxin at 0, 1, 3, or 9 ppm from gestation day 6 to day 21 on weaning after
      delivery. Offspring were maintained through postnatal day (PND) 77 without T-2
      toxin exposure. In the hippocampal dentate gyrus of male PND 21 offspring,
      GFAP(+) and BLBP(+) type-1 stem cells and PAX6(+) and TBR2(+) type-2 progenitor
      cells decreased in the subgranular zone (SGZ) at 9 and >=3 ppm, respectively, in
      parallel with increased apoptosis at >=3 ppm. In the dentate hilus, reelin(+)
      gamma-aminobutyric acid (GABA)-ergic interneurons increased at 9 ppm, suggesting
      reflection of neuronal mismigration. T-2 toxin decreased transcript levels of
      cholinergic and glutamate receptor subunits (Chrna4, Chrnb2 and Gria2) and
      glutamate transporter (Slc17a6) in the dentate gyrus, suggesting decreased
      cholinergic signals on hilar GABAergic interneurons innervating type-2 cells and
      decreased glutamatergic signals on type-1 and type-2 cells. T-2 toxin decreased
      SGZ cells expressing stem cell factor (SCF) and increased cells accumulating
      malondialdehydes. Neurogenesis-related changes disappeared on PND 77, suggesting
      that T-2 toxin reversibly affects neurogenesis by inducing apoptosis of type-1
      and type-2 cells with different threshold levels. Decreased cholinergic and
      glutamatergic signals may decrease type-2 cells at >=3 ppm. Additionally,
      decreased SCF/c-Kit interactions and increased oxidative stress may decrease type
      1 and type-2 cells at 9 ppm. The no-observed-adverse-effect level for offspring
      neurogenesis was determined to be 1 ppm (0.14-0.49 mg/kg body weight/day). 

PMID- 26314265
TI  - Overexpression and gene amplification of both ERBB2 and EGFR in an esophageal
      squamous cell carcinoma revealed by fluorescence in situ hybridization, multiplex
      ligation-dependent probe amplification and immunohistochemistry.
AB  - EGFR and ERBB2 belong to the EGFR gene family. In esophageal squamous cell
      carcinomas (SCCs), amplification of EGFR or ERBB2 is usually mutually exclusive.
      EGFR amplification occurs in approximately 15% of SCCs, ERBB2 occurs in less than
      5%. Here, we report the co-amplification of EGFR and ERBB2 in an ulcerative and
      infiltrating-type SCC that measured approximately 4.2 * 2.7 * 1.2 cm with a
      superficial lesion occurring in the thoracic esophagus of a 72-year-old man.
      Multiplex ligation-dependent probe amplification using representative tumor
      sections showed gain of CCND1 and coincident amplification of ERBB2 or EGFR or
      neither. Immunohistochemistry and fluorescence in situ hybridization revealed
      that the tumor comprised three cancer-cell populations: well-differentiated SCC
      with high-level ERBB2 amplification and ERBB2 overexpression, more infiltrative
      poorly-differentiated SCC with high-level EGFR amplification and EGFR
      overexpression, and poorly-differentiated SCC lacking any ERBB2 or EGFR
      abnormality. These three populations each had low-level CCND1 amplification and
      nuclear cyclin D1 overexpression. This histological topology and gene
      amplification combinations suggested that genetic instability first produced
      CCND1 amplification, and then ERBB2 or EGFR gene amplification occurred. It is
      further speculated that during cancer progression and clonal selection indecisive
      predominance of either clone caused the rare co-amplification of ERBB2 and EGFR
      in a single chimeric tumor.

PMID- 26314266
TI  - Cationic mononuclear ruthenium carboxylates as catalyst prototypes for self
      induced hydrogenation of carboxylic acids.
AB  - Carboxylic acids are ubiquitous in bio-renewable and petrochemical sources of
      carbon. Hydrogenation of carboxylic acids to yield alcohols produces water as the
      only byproduct, and thus represents a possible next generation, sustainable
      method for the production of these alternative energy carriers/platform chemicals
      on a large scale. Reported herein are molecular insights into cationic
      mononuclear ruthenium carboxylates ([Ru(OCOR)](+)) as prototypical catalysts for
      the hydrogenation of carboxylic acids. The substrate-derived coordinated
      carboxylate was found to function initially as a proton acceptor for the
      heterolytic cleavage of dihydrogen, and subsequently also as an acceptor for the
      hydride from [Ru-H](+), which was generated in the first step (self-induced
      catalysis). The hydrogenation proceeded selectively and at high levels of
      functional group tolerance, a feature that is challenging to achieve with
      existing heterogeneous/homogeneous catalyst systems. These fundamental insights
      are expected to significantly benefit the future development of metal carboxylate
      catalysed hydrogenation processes of bio-renewable resources. 

PMID- 26314267
TI  - [Lysosomal storage diseases: A brief summary].
AB  - BACKGROUND: A considerable number of lysosomal storage diseases (LSD), which can
      occur at any age in life, should be included in the differential diagnosis of
      histiocytic diseases. OBJECTIVE: To what extent can pathologists contribute to
      the diagnostics of LSD? MATERIAL AND METHODS: In material collected from LSD,
      morphological storage phenomena in some disease forms, particularly in
      histiocytic cells from bone marrow smears and some tissues are highlighted,
      presented and described. Due to the multitude and heterogeneity of LSDs this list
      is by no means exhaustive. RESULTS: In Gaucher disease, the forms of Niemann-Pick
      disease, cholesteryl ester storage disease (CESD), GM1 gangliosidosis and other
      LSDs, the histiocytic storage cells seen, for example, in bone marrow smears can
      be finely and ultrastructurally differentiated. Thereby, not only the presence of
      an LSD in general but also some individual types of LSD can be identified, even
      though preliminarily. To confirm the diagnosis the genetic and sometimes
      biochemical analysis of blood samples or fibroblast cultures from patients is
      usually required. CONCLUSION: The pathologist may be the first to suspect LSD and
      this applies to LSDs that show storage histiocytes or one of a number of other
      LSDs in which only minor or absent storage is seen in histiocytes but marked
      storage phenomena are found in other cell systems. Some of the numerous,
      extremely heterogeneous LSDs may, however, be overlooked as detailed knowledge of
      the generally rare LSDs is the domain of LSD specialists. Clinicians,
      pathologists, geneticists and biochemists should cooperate in solving the
      diagnostic problems.

PMID- 26314268
TI  - [Acute leukemia in adults].
AB  - BACKGROUND: The prognosis of adult patients with acute leukemia has continuously
      improved over the years due to the introduction of new diagnostic and therapeutic
      procedures and progress in the field of supportive therapy. METHODS: This article
      gives an overview of the currently available options and the clinical approach to
      the diagnostics and therapy of acute leukemia. RESULTS: The standardization as
      well as improvements in diagnostic procedures, in particular by immunocytological
      and genetic procedures, allow a more rapid determination of the exact diagnosis.
      In addition to age and performance status of patients, an established panel of
      cytogenetic and molecular markers allows an individual risk stratification for
      selecting the most appropriate therapeutic procedure for each patient. In acute
      myeloid leukemia (AML) younger patients with genetically determined intermediate
      and poor risk status benefit from allogeneic stem cell transplantation whereas
      patients in the low risk group are still primarily treated with conventional
      induction chemotherapy with anthracycline and cytarabine. The poor prognosis of
      elderly patients with AML has been improved by the development of stem cell
      transplantation procedures with reduced intensity conditioning and for patients
      not suitable for stem cell transplantation, the introduction of less toxic
      demethylating substances allows a substantial improvement in outcome and quality
      of life compared to cytoreductive therapy alone. The additional role of targeted
      therapies in AML is still under investigation. In adult patients with acute
      lymphoblastic leukemia (ALL), the standard systemic therapy still consists of
      complex cytotoxic regimens which have been modified from pediatric protocols.
      Biologically and genetically determined subgroups of ALL patients as well as poor
      responders, who can be identified by the detection of significant molecular
      determined residual disease (MRD) after standard therapy, benefit from allogeneic
      transplantation in first remission. In patients with bcr-abl positive ALL, the
      implementation of first and second generation tyrosine kinase inhibitors has led
      to rapidly rising response rates and less toxicity. Patients with relapsed ALL
      may benefit from new molecular options, e.g. bispecific antibodies. Additionally,
      improved standardization and supportive care, particularly due to the
      introduction of modern antimycotic agents, increase the treatment options and
      improve the prognosis of patients with acute leukemia. CONCLUSION: The improved
      diagnostic and therapeutic options for patients with acute leukemia require a
      complex management. Currently only subgroups of patients benefit from molecular
      targeted therapeutic strategies. Due to this increasing complexity in the
      management, patients with acute leukemia should be treated in academic centers
      and within clinical trials.

PMID- 26314269
TI  - Sonochemical Synthesis of Layered Copper Hydroxy Nitrate Nanosheets.
AB  - Sonochemical reduction of copper nitrate, using 20 kHz ultrasound in aqueous
      solutions in the presence of urea, led to the formation of layered copper hydroxy
      nitrate nanosheets, as evidenced by scanning and transmission electron microscopy
      images. Fourier-transform infrared, X-ray diffraction, and X-ray photoelectron
      spectroscopy analyses were used to characterize layered Cu2(OH)3NO3 nanosheets.
      The ultrasound-assisted progressive hydrolysis of urea and in situ formation of
      Cu(0) through the sonochemical reduction process induced homogeneous nucleation
      and crystallization of layered Cu2(OH)3NO3 nanosheets.

PMID- 26314271
TI  - Optimized spherical manganese oxide-ferroferric oxide-tin oxide ternary
      composites as advanced electrode materials for supercapacitors.
AB  - Inexpensive MnO2 is a promising material for supercapacitors (SCs), but its
      application is limited by poor electrical conductivity and low specific surface
      area. We design and fabricate hierarchical MnO2-based ternary composite
      nanostructures showing superior electrochemical performance via doping with
      electrochemically active Fe3O4 in the interior and electrically conductive SnO2
      nanoparticles in the surface layer. Optimization composition results in a MnO2
      Fe3O4-SnO2 composite electrode material with 5.9 wt.% Fe3O4 and 5.3 wt.% SnO2,
      leading to a high specific areal capacitance of 1.12 F cm(-2) at a scan rate of 5
      mV s(-1). This is two to three times the values for MnO2-based binary
      nanostructures at the same scan rate. The low amount of SnO2 almost doubles the
      capacitance of porous MnO2-Fe3O4 (before SnO2 addition), which is attributed to
      an improved conductivity and remaining porosity. In addition, the optimal ternary
      composite has a good rate capability and an excellent cycling performance with
      stable capacitance retention of ~90% after 5000 charge/discharge cycles at 7.5 mA
      cm(-2). All-solid-state SCs are assembled with such electrodes using polyvinyl
      alcohol/Na2SO4 electrolyte. An integrated device made by connecting two identical
      SCs in series can power a light-emitting diode indicator for more than 10 min.

PMID- 26314272
TI  - Does hostile rumination mediate the associations between reported child abuse,
      parenting characteristics and borderline features in adulthood?
AB  - This cross-sectional study investigated whether hostile rumination mediated the
      association between several indicators of a negative childhood environment
      (retrospectively reported child abuse and perceived parental care and
      overprotection) and borderline features. Community participants (N = 524)
      completed self-report measures in the laboratory. Results showed that adults
      exhibiting borderline features reported less parental care and more parental
      overprotection, as well as greater abuse. Additionally, hostile rumination
      statistically mediated the associations between all childhood environmental
      variables and borderline features, even controlling for depressive symptoms,
      alcohol use and impulsivity. Although cross-sectional data cannot test causal
      mediation, this pattern of results provides preliminary evidence that hostile
      rumination may partially account for the well-established connection between
      negative environments and borderline features. Future directions, including a
      discussion of longitudinal and experimental work that might help build on and
      strengthen the current findings, are explored.

PMID- 26314270
TI  - Podophyllotoxin acetate triggers anticancer effects against non-small cell lung
      cancer cells by promoting cell death via cell cycle arrest, ER stress and
      autophagy.
AB  - We previously reported that podophyllotoxin acetate (PA) radiosensitizes NCI-H460
      cells. Here, we confirmed that PA treatment also induces cell death among two
      other non-small cell lung cancer (NSCLC) cell lines: NCI-H1299 and A549 cells
      (IC50 values = 7.6 and 16.1 nM, respectively). Our experiments further showed
      that PA treatment was able to induce cell death via various mechanisms. First, PA
      dose-dependently induced cell cycle arrest at G2/M phase, as shown by
      accumulation of the mitosis-related proteins, p21, survivin and Aurora B. This
      G2/M phase arrest was due to the PA-induced inhibition of microtubule
      polymerization. Together, the decreased microtubule polymerization and increased
      cell cycle arrest induced DNA damage (reflected by accumulation of gamma-H2AX)
      and triggered the induction of intrinsic and extrinsic apoptotic pathways, as
      shown by the time-dependent activations of caspase-3, -8 and -9. Second, PA time
      dependently activated the pro-apoptotic ER stress pathway, as evidenced by
      increased expression levels of BiP, CHOP, IRE1-alpha, phospho-PERK, and phospho
      JNK. Third, PA activated autophagy, as reflected by time-dependent increases in
      the expression levels of beclin-1, Atg3, Atg5 and Atg7, and the cleavage of LC3.
      Collectively, these results suggest a model wherein PA decreases microtubule
      polymerization and increases cell cycle arrest, thereby inducing apoptotic cell
      death via the activation of DNA damage, ER stress and autophagy.

PMID- 26314273
TI  - Biological Chitin-MOF Composites with Hierarchical Pore Systems for Air
      Filtration Applications.
AB  - Metal-organic frameworks (MOFs) are promising materials for gas-separation and
      air-filtration applications. However, for these applications, MOF crystallites
      need to be incorporated in robust and manageable support materials. We used
      chitin-based networks from a marine sponge as a non-toxic, biodegradable, and low
      weight support material for MOF deposition. The structural properties of the
      material favor predominant nucleation of the MOF crystallites at the inside of
      the hollow fibers. This composite has a hierarchical pore system with surface
      areas up to 800 m(2)  g(-1) and pore volumes of 3.6 cm(3)  g(-1) , allowing good
      transport kinetics and a very high loading of the active material. Ammonia break
      through experiments highlight the accessibility of the MOF crystallites and the
      adsorption potential of the composite indicating their high potential for
      filtration applications for toxic industrial gases.

PMID- 26314274
TI  - Developing a one-stop tinnitus service: outcomes of a joined up management
      strategy: a retrospective observational cohort study.
AB  - RATIONALE, AIMS AND OBJECTIVES: The pressure to deliver quality care with finite
      resources means that dealing with single-symptom conditions like tinnitus in an
      efficient and individualized manner has never been more important. Both primary
      and secondary care practitioners have an obligation to explore efficient delivery
      of simple management pathways. Commissioners of health care are in a unique
      position to affect evidence-based strategic change in the management of
      uncomplicated tinnitus. This study is an attempt to explore one such option. We
      present the outcomes of a tinnitus patient pathway designed for one-stop
      management, thereby minimizing unnecessary additional appointments. METHOD: A
      retrospective observational cohort study of 452 patients referred to a NHS one
      stop tinnitus clinic from 2008 to 2012. Clinical care guided was through the use
      of a structured approach to history taking, neurotological examination and
      management. RESULTS: 294 out of 452 (65%) of patients referred had unilateral
      tinnitus. The most common associated complaints were hearing loss (387/452, 86%)
      and hyperacusis (329/452, 73%). 210 (46%) of patients had their presenting
      complaint dealt with in a single clinic visit. CONCLUSION: A structured system
      for referral and management of tinnitus within the health system ensures patients
      have timely access to evidence-based investigation and treatment. A consistent
      approach to imaging aimed at identifying retrocochlear pathology can benefit
      patients through early diagnosis of central pathology and the reassurance
      provided by a negative scan.

PMID- 26314275
TI  - Efficacy of thiopurines and adalimumab in preventing Crohn's disease recurrence
      in high-risk patients - a POCER study analysis.
AB  - BACKGROUND: Crohn's disease recurs in the majority of patients after intestinal
      resection. AIM: To compare the relative efficacy of thiopurines and anti-TNF
      therapy in patients at high risk of disease recurrence. METHODS: As part of a
      larger study comparing post-operative management strategies, patients at high
      risk of recurrence (smoker, perforating disease, >=2nd operation) were treated
      after resection of all macroscopic disease with 3 months metronidazole together
      with either azathioprine 2 mg/kg/day or mercaptopurine 1.5 mg/kg/day. Thiopurine
      intolerant patients received adalimumab induction then 40 mg fortnightly.
      Patients underwent colonoscopy at 6 months with endoscopic recurrence assessed
      blind to treatment. RESULTS: A total of 101 patients [50% male; median (IQR) age
      36 (25-46) years] were included. There were no differences in disease history
      between thiopurine- and adalimumab-treated patients. Fifteen patients withdrew
      prior to 6 months, five due to symptom recurrence (of whom four were
      colonoscoped). Endoscopic recurrence (Rutgeerts score i2-i4) occurred in 33 of 73
      (45%) thiopurine vs. 6 of 28 (21%) adalimumab-treated patients [intention-to
      treat (ITT); P = 0.028] or 24 of 62 (39%) vs. 3 of 24 (13%) respectively [per
      protocol analysis (PPA); P = 0.020]. Complete mucosal endoscopic normality
      (Rutgeerts i0) occurred in 17/73 (23%) vs. 15/28 (54%) (ITT; P = 0.003) and in
      27% vs. 63% (PPA; P = 0.002). The most advanced disease (Rutgeerts i3 and i4)
      occurred in 8% vs. 4% (thiopurine vs. adalimumab). CONCLUSIONS: In Crohn's
      disease patients at high risk of post-operative recurrence adalimumab is superior
      to thiopurines in preventing early disease recurrence.

PMID- 26314277
TI  - Autoimmune Arthropathy and Uveitis as Complications of Programmed Death 1
      Inhibitor Treatment.

PMID- 26314276
TI  - Retinal synaptic regeneration via microfluidic guiding channels.
AB  - In vitro culture of dissociated retinal neurons is an important model for
      investigating retinal synaptic regeneration (RSR) and exploring potentials in
      artificial retina. Here, retinal precursor cells were cultured in a microfluidic
      chip with multiple arrays of microchannels in order to reconstruct the retinal
      neuronal synapse. The cultured retinal cells were physically connected through
      microchannels. Activation of electric signal transduction by the cells through
      the microchannels was demonstrated by administration of glycinergic factors. In
      addition, an image-based analytical method was used to quantify the synaptic
      connections and to assess the kinetics of synaptic regeneration. The rate of RSR
      decreased significantly below 100 MUM of inhibitor glycine and then approached to
      a relatively constant level at higher concentrations. Furthermore, RSR was
      enhanced by chemical stimulation with potassium chloride. Collectively, the
      microfluidic synaptic regeneration chip provides a novel tool for high-throughput
      investigation of RSR at the cellular level and may be useful in quality control
      of retinal precursor cell transplantation. 

PMID- 26314279
TI  - Precise correlation between structural and electrophysiological disturbances in
      MADSAM neuropathy.
AB  - Multifocal acquired demyelinating sensory and motor neuropathy is characterised
      by multifocal clinical deficits. Imaging studies have identified multifocal
      enlargements of nerve trunks, but a precise correlation between structural
      abnormalities and electrophysiological dysfunction has not been elucidated. Two
      patients diagnosed with multifocal acquired demyelinating sensory and motor
      neuropathy were evaluated with nerve conduction studies, including short segment
      nerve conduction studies to precisely localise motor conduction block, and
      ultrasound studies of corresponding nerve trunks. Motor conduction block was
      identified in each patient (upper limb nerves in two patients), superimposed on
      additional demyelinating neurophysiological features. Upper limb ultrasound
      studies demonstrated focal nerve enlargement that precisely correlated with
      neurophysiological conduction block. The results of this study suggest that
      factors contributing to focal structural abnormalities in multifocal acquired
      demyelinating sensory and motor neuropathy are also those that produce conduction
      block. 

PMID- 26314278
TI  - Does parental divorce moderate the heritability of body dissatisfaction? An
      extension of previous gene-environment interaction effects.
AB  - OBJECTIVE: Previous research suggests that parental divorce moderates genetic
      influences on body dissatisfaction. Specifically, the heritability of body
      dissatisfaction is higher in children of divorced versus intact families,
      suggesting possible gene-environment interaction effects. However, prior research
      is limited to a single, self-reported measure of body dissatisfaction. The
      primary aim of this study was to examine whether these findings extend to a
      different dimension of body dissatisfaction: body image perceptions. METHOD:
      Participants were 1,534 female twins from the Minnesota Twin Family Study, aged
      16-20 years. The Body Rating Scale (BRS) was used to assess body image
      perceptions. RESULTS: Although BRS scores were heritable in twins from divorced
      and intact families, the heritability estimates in the divorced group were not
      significantly greater than estimates in the intact group. However, there were
      differences in nonshared environmental effects, where the magnitude of these
      environmental influences was larger in the divorced as compared with the intact
      families. DISCUSSION: Different dimensions of body dissatisfaction (i.e.,
      negative self-evaluation versus body image perceptions) may interact with
      environmental risk, such as parental divorce, in discrete ways. Future research
      should examine this possibility and explore differential gene-environment
      interactions using diverse measures.

PMID- 26314280
TI  - Neural stem cell therapy for cancer.
AB  - Cancers of the brain remain one of the greatest medical challenges. Traditional
      surgery and chemo-radiation therapy are unable to eradicate diffuse cancer cells
      and tumor recurrence is nearly inevitable. In contrast to traditional
      regenerative medicine applications, engineered neural stem cells (NSCs) are
      emerging as a promising new therapeutic strategy for cancer therapy. The tumor
      homing properties allow NSCs to access both primary and invasive tumor foci,
      creating a novel delivery platform. NSCs engineered with a wide array of
      cytotoxic agents have been found to significantly reduce tumor volumes and
      markedly extend survival in preclinical models. With the recent launch of new
      clinical trials, the potential to successfully manage cancer in human patients
      with cytotoxic NSC therapy is moving closer to becoming a reality.

PMID- 26314281
TI  - Bioengineering functional human sphincteric and non-sphincteric gastrointestinal
      smooth muscle constructs.
AB  - Digestion and motility of luminal content through the gastrointestinal (GI) tract
      are achieved by cooperation between distinct cell types. Much of the 3
      dimensional (3D) in vitro modeling used to study the GI physiology and disease
      focus solely on epithelial cells and not smooth muscle cells (SMCs). SMCs of the
      gut function either to propel and mix luminal contents (phasic; non-sphincteric)
      or to act as barriers to prevent the movement of luminal materials (tonic;
      sphincteric). Motility disorders including pyloric stenosis and chronic
      intestinal pseudoobstruction (CIPO) affect sphincteric and non-sphincteric SMCs,
      respectively. Bioengineering offers a useful tool to develop functional GI tissue
      mimics that possess similar characteristics to native tissue. The objective of
      this study was to bioengineer 3D human pyloric sphincter and small intestinal
      (SI) constructs in vitro that recapitulate the contractile phenotypes of
      sphincteric and non-sphincteric human GI SMCs. Bioengineered 3D human pylorus and
      circular SI SMC constructs were developed and displayed a contractile phenotype.
      Constructs composed of human pylorus SMCs displayed tonic SMC characteristics,
      including generation of basal tone, at higher levels than SI SMC constructs which
      is similar to what is seen in native tissue. Both constructs contracted in
      response to potassium chloride (KCl) and acetylcholine (ACh) and relaxed in
      response to vasoactive intestinal peptide (VIP). These studies provide the first
      bioengineered human pylorus constructs that maintain a sphincteric phenotype.
      These bioengineered constructs provide appropriate models to study motility
      disorders of the gut or replacement tissues for various GI organs.

PMID- 26314282
TI  - Lenalidomide for the Treatment of Low- or Intermediate-1-Risk Myelodysplastic
      Syndromes Associated with Deletion 5q Cytogenetic Abnormality: An Evidence Review
      of the NICE Submission from Celgene.
AB  - The National Institute for Health and Care Excellence (NICE) invited the
      manufacturer of lenalidomide (Celgene) to submit evidence of the clinical and
      cost effectiveness of the drug for treating adults with myelodysplastic syndromes
      (MDS) associated with deletion 5q cytogenetic abnormality, as part of the
      Institute's single technology appraisal (STA) process. Kleijnen Systematic
      Reviews Ltd (KSR), in collaboration with Erasmus University Rotterdam, was
      commissioned to act as the Evidence Review Group (ERG). This paper describes the
      company's submission, the ERG review, and the NICE's subsequent decisions. The
      ERG reviewed the evidence for clinical and cost effectiveness of the technology,
      as submitted by the manufacturer to the NICE. The ERG searched for relevant
      additional evidence and validated the manufacturer's decision analytic model to
      examine the robustness of the cost-effectiveness results. Clinical effectiveness
      was obtained from a three-arm, European, randomized, phase III trial among red
      blood cell (RBC) transfusion-dependent patients with low-/intermediate-1-risk
      del5q31 MDS. The primary endpoint was RBC independence for >=26 weeks, and was
      reached by a higher proportion of patients in the lenalidomide 10 and 5 mg groups
      compared with placebo (56.1 and 42.6 vs 5.9 %, respectively; both p < 0.001). The
      option of dose adjustments after 16 weeks due to dose-limiting toxicities or lack
      of response made long-term effectiveness estimates unreliable, e.g. overall
      survival (OS). The de novo model of the manufacturer included a Markov state
      transition cost-utility model implemented in Microsoft Excel. The base-case
      incremental cost-effectiveness ratio (ICER) of the manufacturer was L56,965. The
      ERG assessment indicated that the modeling structure represented the course of
      the disease; however, a few errors were identified and some of the input
      parameters were challenged. In response to the appraisal documentation, the
      company revised the economic model, which increased the ICER to L68,125 per
      quality-adjusted life-year. The NICE Appraisal Committee (AC) did not recommend
      lenalidomide as a cost-effective treatment. Subsequently, the manufacturer
      submitted a Patient Access Scheme (PAS) that provided lenalidomide free of charge
      for patients who remained on treatment after 26 cycles. This PAS improved the
      ICER to L25,300, although the AC considered the proportion of patients who
      received treatment beyond 26 cycles, and hence the ICER, to be uncertain.
      Nevertheless, the AC accepted a commitment from the manufacturer to publish, once
      available, data on the proportion of patients eligible for the PAS, and believed
      this provided reassurance that lenalidomide was a cost-effective treatment for
      low- or intermediate-1-risk MDS patients. 

PMID- 26314283
TI  - The Authors' Reply: Comment on "Healthy Decisions: Towards Uncertainty Tolerance
      in Healthcare Policy".

PMID- 26314286
TI  - Supramicrosurgical lymphatic-venous anastomosis for postsurgical subcutaneous
      lymphocele treatment.
AB  - Postsurgical subcutaneous lymphocele is caused by accidental lesion of a
      lymphatic vessel that keeps on flowing lymph under the scar. Traditional
      treatments include aspiration and compression, with probable recurrence, and
      sclerotherapy which destroys both lymphatic cyst and vessel, creating risk of
      lymphedema. We describe the case of a postsurgical subcutaneous lymphocele of the
      left leg that was treated by supramicrosurgical lympatic-venous anastomosis. A
      single anastomosis was performed end-to-end, between one lymphatic vessel,
      individuated through indocyanine green lymphography, and one subcutaneous vein,
      distally to the lymphocele, under sedation and local anesthesia. Postoperative
      course was uneventful; the lymphocele completely resolved and never recurred
      during the nine months followup. This technique may heal the lymphocele with no
      impairing of lymph drainage function.

PMID- 26314285
TI  - A new equation to estimate temperature-corrected PaCO2 from PET CO2 during
      exercise in normoxia and hypoxia.
AB  - End-tidal PCO2 (PET CO2 ) has been used to estimate arterial pressure CO2 (Pa CO2
      ). However, the influence of blood temperature on the Pa CO2 has not been taken
      into account. Moreover, there is no equation validated to predict Pa CO2 during
      exercise in severe acute hypoxia. To develop a new equation to predict
      temperature-corrected Pa CO2 values during exercise in normoxia and severe acute
      hypoxia, 11 volunteers (21.2 +/- 2.1 years) performed incremental exercise to
      exhaustion in normoxia (Nox, PI O2 : 143 mmHg) and hypoxia (Hyp, PI O2 : 73
      mmHg), while arterial blood gases and temperature (ABT) were simultaneously
      measured together with end-tidal PCO2 (PET CO2 ). The Jones et al. equation
      tended to underestimate the temperature corrected (tc) Pa CO2 during exercise in
      hypoxia, with greater deviation the lower the Pa CO2 tc (r = 0.39, P < 0.05). The
      new equation has been developed using a random-effects regression analysis model,
      which allows predicting Pa CO2 tc both in normoxia and hypoxia: Pa CO2 tc = 8.607
      + 0.716 * PET CO2 [R(2)  = 0.91; intercept SE = 1.022 (P < 0.001) and slope SE =
      0.027 (P < 0.001)]. This equation may prove useful in noninvasive studies of
      brain hemodynamics, where an accurate estimation of Pa CO2 is needed to calculate
      the end-tidal-to-arterial PCO2 difference, which can be used as an index of
      pulmonary gas exchange efficiency. 

PMID- 26314284
TI  - Heart failure induces changes in acid-sensing ion channels in sensory neurons
      innervating skeletal muscle.
AB  - Heart failure is associated with diminished exercise capacity, which is driven,
      in part, by alterations in exercise-induced autonomic reflexes triggered by
      skeletal muscle sensory neurons (afferents). These overactive reflexes may also
      contribute to the chronic state of sympathetic excitation, which is a major
      contributor to the morbidity and mortality of heart failure. Acid-sensing ion
      channels (ASICs) are highly expressed in muscle afferents where they sense
      metabolic changes associated with ischaemia and exercise, and contribute to the
      metabolic component of these reflexes. Therefore, we tested if ASICs within
      muscle afferents are altered in heart failure. We used whole-cell patch clamp to
      study the electrophysiological properties of acid-evoked currents in isolated,
      labelled muscle afferent neurons from control and heart failure (induced by
      myocardial infarction) mice. We found that the percentage of muscle afferents
      that displayed ASIC-like currents, the current amplitudes, and the pH dose
      response relationships were not altered in mice with heart failure. On the other
      hand, the biophysical properties of ASIC-like currents were significantly
      different in a subpopulation of cells (40%) from heart failure mice. This
      population displayed diminished pH sensitivity, altered desensitization kinetics,
      and very fast recovery from desensitization. These unique properties define these
      channels within this subpopulation of muscle afferents as being heteromeric
      channels composed of ASIC2a and -3 subunits. Heart failure induced a shift in the
      subunit composition of ASICs within muscle afferents, which significantly altered
      their pH sensing characteristics. These results might, in part, contribute to the
      changes in exercise-mediated reflexes that are associated with heart failure.

PMID- 26314287
TI  - Connectivity in grey reef sharks (Carcharhinus amblyrhynchos) determined using
      empirical and simulated genetic data.
AB  - Grey reef sharks (Carcharhinus amblyrhynchos) can be one of the numerically
      dominant high order predators on pristine coral reefs, yet their numbers have
      declined even in the highly regulated Australian Great Barrier Reef (GBR) Marine
      Park. Knowledge of both large scale and fine scale genetic connectivity of grey
      reef sharks is essential for their effective management, but no genetic data are
      yet available. We investigated grey reef shark genetic structure in the GBR
      across a 1200 km latitudinal gradient, comparing empirical data with models
      simulating different levels of migration. The empirical data did not reveal any
      genetic structuring along the entire latitudinal gradient sampled, suggesting
      regular widespread dispersal and gene flow of the species throughout most of the
      GBR. Our simulated datasets indicate that even with substantial migrations (up to
      25% of individuals migrating between neighboring reefs) both large scale genetic
      structure and genotypic spatial autocorrelation at the reef scale were
      maintained. We suggest that present migration rates therefore exceed this level.
      These findings have important implications regarding the effectiveness of
      networks of spatially discontinuous Marine Protected Areas to protect reef
      sharks. 

PMID- 26314288
TI  - Irreversible electron attachment--a key to DNA damage by solvated electrons in
      aqueous solution.
AB  - The TYT and TXT trimeric oligonucleotides, where X stands for a native
      nucleobase, T (thymine), C (cytosine), A (adenine), or G (guanine), and Y
      indicates a brominated analogue of the former, were irradiated with ionizing
      radiation generated by a (60)Co source in aqueous solutions containing Tris as a
      hydroxyl radical scavenger. In the past, these oligomers were bombarded with low
      energy electrons under an ultra-high vacuum and significant damage to TXT trimers
      was observed. However, in aqueous solution, hydrated electrons do not produce
      serious damage to TXT trimers although the employed radiation dose exceeded many
      times the doses used in radiotherapy. Thus, our studies demonstrate unequivocally
      that hydrated electrons, which are the major form of electrons generated during
      radiotherapy, are a negligible factor in damage to native DNA. It was also
      demonstrated that all the studied brominated nucleobases have a potential to
      sensitize DNA under hypoxic conditions. Strand breaks, abasic sites and the
      products of hydroxyl radical attachment to nucleobases have been identified by
      HPLC and LC-MS methods. Although all the bromonucleobases lead to DNA damage
      under the experimental conditions of the present work, bromopyrimidines seem to
      be the radiosensitizers of choice since they lead to more strand breaks than
      bromopurines. 

PMID- 26314289
TI  - Cost-Utility and Cost-Effectiveness Analyses of Face-to-Face Versus Telephone
      Based Nonpharmacologic Multidisciplinary Treatments for Patients With Generalized
      Osteoarthritis.
AB  - OBJECTIVE: To evaluate, from a societal perspective, the cost utility and cost
      effectiveness of a nonpharmacologic face-to-face treatment program compared with
      a telephone-based treatment program for patients with generalized osteoarthritis
      (GOA). METHODS: An economic evaluation was carried out alongside a randomized
      clinical trial involving 147 patients with GOA. Program costs were estimated from
      time registrations. One-year medical and nonmedical costs were estimated using
      cost questionnaires. Quality-adjusted life years (QALYs) were estimated using the
      EuroQol (EQ) classification system, EQ rating scale, and the Short Form 6D (SF
      6D). Daily function was measured using the Health Assessment Questionnaire (HAQ)
      disability index (DI). Cost and QALY/effect differences were analyzed using
      multilevel regression analysis and cost-effectiveness acceptability curves.
      RESULTS: Medical costs of the face-to-face treatment and telephone-based
      treatment were estimated at ?387 and ?252, respectively. The difference in total
      societal costs was nonsignificantly in favor of the face-to-face program
      (difference ?708; 95% confidence interval [95% CI] -?5,058, ?3,642). QALYs were
      similar for both groups according to the EQ, but were significantly in favor of
      the face-to-face group, according to the SF-6D (difference 0.022 [95% CI 0.000,
      0.045]). Daily function was similar according to the HAQ DI. Since both societal
      costs and QALYs/effects were in favor of the face-to-face program, the economic
      assessment favored this program, regardless of society's willingness to pay.
      There was a 65-90% chance that the face-to-face program had better cost utility
      and a 60-70% chance of being cost effective. CONCLUSION: This economic evaluation
      from a societal perspective showed that a nonpharmacologic, face-to-face
      treatment program for patients with GOA was likely to be cost effective, relative
      to a telephone-based program.

PMID- 26314291
TI  - Incorporating Clinical and Translational Science into the Undergraduate Medical
      Education Curriculum.

PMID- 26314292
TI  - Elevated IL-1beta levels in anti-Ro/SSA connective tissue diseases patients with
      prolonged corrected QTc interval.
AB  - OBJECTIVES: Patients with systemic lupus erythematosus (SLE) and primary
      Sjogren's syndrome (pSS) have increased IL-1beta levels. IL-1beta and other pro
      inflammatory cytokines have a modulating activity on cardiac ion channels and
      have been associated with increased arrhythmic risk in rheumatoid arthritis
      patients. Likewise, adult patients with connective tissue diseases (CTDs) may
      have prolonged QTc intervals associated with the presence of anti-Ro/SSA
      antibodies. Our objective was to evaluate the presence of serum IL-1beta in
      subjects with CTDs, in relation to the presence of anti-Ro/SSA antibodies and QTc
      interval duration. METHODS: 12-lead electrocardiograms (ECG) were performed and
      blood was withdrawn, measuring electrolytes, IL-1beta anti-Ro/SSA antibodies by
      ELISA in 73 patients with CTDs. RESULTS: 55 patients were anti-Ro/SSA positive
      and 18 were anti-Ro/SSA negative. Patients with anti-Ro/SSA positive antibodies
      had a significantly greater median IL-1beta serum level: 7.29 (range: 0.17-17.3
      pg/ml) compared to patients with anti-Ro/SSA negative antibodies whose median
      was: 1.67 (range 0.55-4.12 pg/ml) p<0.001. The mean QTc interval values obtained
      in both groups were not significantly different (417.7+/-23.1 vs. 414.7+/-21.2,
      p=0.63). The QTc interval was prolonged in 11 (20%) patients, who were all anti
      Ro/SSA positive versus 0 (0 %) in anti-Ro/SSA negative patients p=0.05. Median IL
      1beta levels were: 8.7 (range: 2.69-15.1 pg/ml) in patients with prolonged QTc
      interval versus median: 5.0 (range: 0.17-17.3 pg/ml) in those with normal QTc
      interval values (<440ms) p=0.006. CONCLUSIONS: IL-1beta is elevated in patients
      with CTDs that have both anti-Ro/SSA antibodies and prolonged QTc intervals.

PMID- 26314294
TI  - Debate: should we use variable adjusted life displays (VLAD) to identify
      variations in performance in general surgery?
AB  - BACKGROUND: The recent push for the publication of individual surgeon outcomes
      underpins public interest in safer surgery. Conventional, retrospective
      assessment of surgical performance without continuous monitoring may lead to
      delays in identifying poor performance or recognition of practices that lead to
      be better than expected performance. DISCUSSION: The variable life adjusted
      display (VLAD) is not new, yet is not widely utilised in General Surgery. Its
      construction is simple and if caveats are appreciated the interpretation is
      straightforward, allowing for continuous surveillance of surgical performance.
      SUMMARY: While limitations in the detection of variations in performance are
      appreciated, the VLAD could represent a more useful tool for monitoring
      performance.

PMID- 26314293
TI  - Comparison of 6% hydroxyethyl starch and 5% albumin for volume replacement
      therapy in patients undergoing cystectomy (CHART): study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: The use of artificial colloids is currently controversial, especially
      in Central Europe Several studies demonstrated a worse outcome in intensive care
      unit patients with the use of hydroxyethyl starch. This recently even led to a
      drug warning about use of hydroxyethyl starch products in patients admitted to
      the intensive care unit. The data on hydroxyethyl starch in non-critically ill
      patients are insufficient to support perioperative use. METHODS/DESIGN: We are
      conducting a single-center, open-label, randomized, comparative trial with two
      parallel patient groups to compare human albumin 5% (test drug) with hydroxyethyl
      starch 6% 130/0.4 (comparator). The primary endpoint is cystatin C ratio,
      calculated as the ratio of the cystatin value at day 90 after surgery relative to
      the preoperative value. Secondary objectives are inter alia the evaluation of the
      influence of human albumin and hydroxyethyl starch on further laboratory chemical
      and clinical parameters, glycocalyx shedding, intensive care unit and hospital
      stay and acute kidney injury as defined by RIFLE criteria (risk of renal
      dysfunction, injury to the kidney, failure of kidney function, loss of kidney
      function, and end-stage kidney disease) criteria. DISCUSSION: There is a general
      lack of evidence on the relative safety and effects of hydroxyethyl starch
      compared with human albumin for volume replacement in a perioperative setting.
      Previously conducted studies of surgical patients in which researchers have
      compared different hydroxyethyl starch products included too few patients to
      properly evaluate clinical important outcomes such as renal function. In the
      present study in a high-risk patient population undergoing a major surgical
      intervention, we will determine if perioperative fluid replacement with human
      albumin 5% will have a long-term advantage over a third-generation hydroxyethyl
      starch 130/0.4 on the progression of renal dysfunction until 90 days after
      surgery. TRIAL REGISTRATION: EudraCT number 2010-018343-34. Registered on 11
      January 2010.

PMID- 26314295
TI  - Clinicians' views of factors of importance for improving the rate of VBAC
      (vaginal birth after caesarean section): a qualitative study from countries with
      high VBAC rates.
AB  - BACKGROUND: The most common reason for caesarean section (CS) is repeat CS
      following previous CS. Vaginal birth after caesarean section (VBAC) rates vary
      widely in different healthcare settings and countries. Obtaining deeper knowledge
      of clinicians' views on VBAC can help in understanding the factors of importance
      for increasing VBAC rates. Interview studies with clinicians and women in three
      countries with high VBAC rates (Finland, Sweden and the Netherlands) and three
      countries with low VBAC rates (Ireland, Italy and Germany) are part of
      'OptiBIRTH', an ongoing research project. The study reported here is based on
      interviews in high VBAC countries. The aim of the study was to investigate the
      views of clinicians working in countries with high VBAC rates on factors of
      importance for improving VBAC rates. METHODS: Individual (face-to-face or
      telephone) interviews and focus group interviews with clinicians (in different
      maternity care settings) in three countries with high VBAC rates were conducted
      during 2012-2013. In total, 44 clinicians participated: 26 midwives and 18
      obstetricians. Five central questions about VBAC were used and interviews were
      analysed using content analysis. The analysis was performed in each country in
      the native language and then translated into English. All data were then analysed
      together and final categories were validated in each country. RESULTS: The
      findings are presented in four main categories with subcategories. First, a
      common approach is needed, including: feeling confident with VBAC, considering
      VBAC as the first alternative, communicating well, working in a team, working in
      accordance with a model and making agreements with the woman. Second,
      obstetricians need to make the final decision on the mode of delivery while
      involving women in counselling towards VBAC. Third, a woman who has a previous CS
      has a similar need for support as other labouring women, but with some extra
      precautions and additional recommendations for her care. Finally, clinicians
      should help strengthen women's trust in VBAC, including building their trust in
      giving birth vaginally, recognising that giving birth naturally is an empowering
      experience for women, alleviating fear and offering extra visits to discuss the
      previous CS, and joining with the woman in a dialogue while leaving the decision
      about the mode of birth open. CONCLUSIONS: This study shows that, according to
      midwives and obstetricians from countries with high VBAC rates, the important
      factors for improving the VBAC rate are related to the structure of the maternity
      care system in the country, to the cooperation between midwives and
      obstetricians, and to the care offered during pregnancy and birth. More research
      on clinicians' perspectives is needed from countries with low, as well as high,
      VBAC rates.

PMID- 26314296
TI  - Opioid Maintenance Treatment--A Call for a Joint European Quality Care Approach.
AB  - AIMS: The aim of this exploratory analysis of European Quality Audit of Opioid
      Treatment data was to identify areas of improvement for current opioid
      maintenance treatment (OMT) approaches. METHODS: Factors facilitating treatment
      entry, retention and refusal were compared between 8 European countries and
      between OMT patient (OMT-P) and active opioid user (AOU) sample groups. Both
      groups were divided into those who had never had OMT before (un-experienced OMT-P
      (n = 573) and AOU (n = 360)) and those who had been maintained at least once
      prior to this investigation (experienced OMT-P (n = 746) and AOU (n = 377)).
      RESULTS: The European comparison showed that motives for starting OMT vary
      distinctly between countries (p <= 0.001). Transnationally, experienced AOU
      reported concerns about their ability to follow treatment rules and negative
      treatment experiences as decisive reasons for staying out of OMT. Greater
      flexibility, less pressure to reduce their treatment dose and greater treatment
      structure were ranked significantly higher by experienced compared to un
      experienced OMT-P as factors that might facilitate treatment retention (p <=
      0.05). CONCLUSION: Increasing awareness of potential shortcomings of OMT delivery
      systems is crucial to optimally match treatment approaches to patient needs and
      also to reduce the considerable economic burden of addiction to society.

PMID- 26314298
TI  - Real-World Experience with Insertable Cardiac Monitors to Find Atrial
      Fibrillation in Cryptogenic Stroke.
AB  - BACKGROUND: The characteristics of atrial fibrillation (AF) episodes in
      cryptogenic stroke patients have recently been explored in carefully selected
      patient populations. However, the incidence of AF among a large, real-world
      population of patients with an insertable cardiac monitor (ICM) placed for the
      detection of AF following a cryptogenic stroke has not been investigated.
      METHODS: Patients in the de-identified Medtronic DiscoveryLinkTM database who
      received an ICM (Reveal LINQTM) for the purpose of AF detection following a
      cryptogenic stroke were included. AF detection rates (episodes >=2 min) were
      quantified using Kaplan-Meier survival estimates at 1 and 6 months and compared
      to the CRYSTAL AF study at 6 months. The time to AF detection and maximum
      duration of AF episodes were also analyzed. RESULTS: A total of 1,247 patients
      (age 65.3 +/- 13.0 years) were followed for 182 (IQR 182-182) days. A total of
      1,521 AF episodes were detected in 147 patients, resulting in AF detection rates
      of 4.6 and 12.2% at 30 and 182 days, respectively, and representing a 37%
      relative increase over that reported in the CRYSTAL AF trial at 6 months. The
      median time to AF detection was 58 (IQR 11-101) days and the median duration of
      the longest detected AF episode was 3.4 (IQR 0.4-11.8) h. CONCLUSIONS: The real
      world incidence of AF among patients being monitored with an ICM after a
      cryptogenic stroke validates the findings of the CRYSTAL AF trial and suggests
      that continuous cardiac rhythm monitoring for periods longer than the current
      guideline recommendation of 30 days may be warranted in the evaluation of
      patients with cryptogenic stroke.

PMID- 26314299
TI  - What Are the Predictive Factors for Gleason Score Upgrade following RP?
AB  - The Gleason score is one of a number of factors used in staging patients
      diagnosed with prostate cancer and in determining the treatment path such
      patients will ultimately follow. However, discrepancies in the Gleason scores
      obtained through biopsy compared with the final pathological staging of specimens
      following radical prostatectomy are not uncommon. Incorrect Gleason scoring can
      potentially influence treatment decisions and therefore, it is imperative that
      research is undertaken to elucidate factors that may be able to predict whether a
      patient's Gleason score might need to be reconsidered. A literature review was
      undertaken in late 2014 to highlight some of these factors that require further
      investigation. 

PMID- 26314297
TI  - Rapid evolution of chemosensory receptor genes in a pair of sibling species of
      orchid bees (Apidae: Euglossini).
AB  - BACKGROUND: Insects rely more on chemical signals (semiochemicals) than on any
      other sensory modality to find, identify, and choose mates. In most insects,
      pheromone production is typically regulated through biosynthetic pathways,
      whereas pheromone sensory detection is controlled by the olfactory system. Orchid
      bees are exceptional in that their semiochemicals are not produced metabolically,
      but instead male bees collect odoriferous compounds (perfumes) from the
      environment and store them in specialized hind-leg pockets to subsequently expose
      during courtship display. Thus, the olfactory sensory system of orchid bees
      simultaneously controls male perfume traits (sender components) and female
      preferences (receiver components). This functional linkage increases the
      opportunities for parallel evolution of male traits and female preferences,
      particularly in response to genetic changes of chemosensory detection (e.g.
      Odorant Receptor genes). To identify whether shifts in pheromone composition
      among related lineages of orchid bees are associated with divergence in
      chemosensory genes of the olfactory periphery, we searched for patterns of
      divergent selection across the antennal transcriptomes of two recently diverged
      sibling species Euglossa dilemma and E. viridissima. RESULTS: We identified 3185
      orthologous genes including 94 chemosensory loci from five different gene
      families (Odorant Receptors, Ionotropic Receptors, Gustatory Receptors, Odorant
      Binding Proteins, and Chemosensory Proteins). Our results revealed that orthologs
      with signatures of divergent selection between E. dilemma and E. viridissima were
      significantly enriched for chemosensory genes. Notably, elevated signals of
      divergent selection were almost exclusively observed among chemosensory receptors
      (i.e. Odorant Receptors). CONCLUSIONS: Our results suggest that rapid changes in
      the chemosensory gene family occurred among closely related species of orchid
      bees. These findings are consistent with the hypothesis that strong divergent
      selection acting on chemosensory receptor genes plays an important role in the
      evolution and diversification of insect pheromone systems.

PMID- 26314301
TI  - Epidemiology of Malignant and Non-Malignant Primary Brain Tumors in Jordan.
AB  - BACKGROUND: There is lack of knowledge on the epidemiological characteristics of
      brain tumors in Middle Eastern countries. The objective of this study was to
      study the epidemiological features of primary brain tumors in Jordan. METHODS: We
      conducted a prospective cohort study incorporating data from 16 hospitals in
      Jordan during a 1 year period (May 1, 2011-April 30, 2012). All primary brain
      tumors diagnosed in Jordan during the study period were identified. The following
      parameters were retrieved from patients' files: age, gender, histological type,
      and location. The demographic data of the country was obtained from the National
      Department of Statistics. RESULTS: A total of 313 primary brain tumors were
      identified during the study period. The incidence of primary brain tumors in
      Jordan among the general population was 5.01 per 100,000 person-years (5.38 in
      females and 4.65 in males). The incidence in pediatric, adult, and elderly
      patients was 2.09, 7.29, and 14.38 per 100,000 person-years, respectively. The
      most common histological types were meningioma (26.2%), glioblastoma (18.9%),
      astrocytoma (14.1%), and pituitary adenoma (9.3%). CONCLUSIONS: The incidence of
      primary brain tumors in the Jordanian population is relatively low, in part due
      to the young age of the general population.

PMID- 26314300
TI  - International veterinary epilepsy task force consensus proposal: outcome of
      therapeutic interventions in canine and feline epilepsy.
AB  - Common criteria for the diagnosis of drug resistance and the assessment of
      outcome are needed urgently as a prerequisite for standardized evaluation and
      reporting of individual therapeutic responses in canine epilepsy. Thus, we
      provide a proposal for the definition of drug resistance and partial therapeutic
      success in canine patients with epilepsy. This consensus statement also suggests
      a list of factors and aspects of outcome, which should be considered in addition
      to the impact on seizures. Moreover, these expert recommendations discuss
      criteria which determine the validity and informative value of a therapeutic
      trial in an individual patient and also suggest the application of individual
      outcome criteria. Agreement on common guidelines does not only render a basis for
      future optimization of individual patient management, but is also a
      presupposition for the design and implementation of clinical studies with highly
      standardized inclusion and exclusion criteria. Respective standardization will
      improve the comparability of findings from different studies and renders an
      improved basis for multicenter studies. Therefore, this proposal provides an in
      depth discussion of the implications of outcome criteria for clinical studies. In
      particular ethical aspects and the different options for study design and
      application of individual patient-centered outcome criteria are considered. 

PMID- 26314302
TI  - Urinary neutrophil gelatinase-associated lipocalin for diagnosis and estimating
      activity in lupus nephritis: a meta-analysis.
AB  - Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is relatively specific
      in lupus nephritis (LN) patients. However, its diagnostic value has not been
      evaluated. The aim of this review was to determine the value of uNGAL for
      diagnosis and estimating activity in LN. A comprehensive search was performed on
      PubMed, EMBASE, Web of Knowledge, Cochrane electronic databases through December
      2014. Meta-analysis of sensitivity and specificity was performed with a random
      effects model. Additionally, summary receiver operating characteristic (SROC)
      curves and area under the curve (AUC) values were calculated. Fourteen studies
      were selected for this review. With respect to diagnosing LN, the pooled
      sensitivity and specificity were 73.6% (95% confidence interval (CI), 61.9-83.3)
      and 78.1% (95% CI, 69.0-85.6), respectively. The SROC-AUC value was 0.8632.
      Regarding estimating LN activity, the pooled sensitivity and specificity were
      66.2% (95% CI, 60.4-71.7) and 62.1% (95% CI, 57.9-66.3), respectively. The SROC
      AUC value was 0.7583. In predicting renal flares, the pooled sensitivity and
      specificity were 77.5% (95% CI, 68.1-85.1) and 65.3% (95% CI, 60.0-70.3),
      respectively. The SROC-AUC value was 0.7756. In conclusion, this meta-analysis
      indicates that uNGAL has relatively fair sensitivity and specificity in
      diagnosing LN, estimating LN activity and predicting renal flares, suggesting
      that uNGAL is a potential biomarker in diagnosing LN and monitoring LN activity. 

PMID- 26314303
TI  - Outcome of Minimally Invasive Distal Metatarsal Metaphyseal Osteotomy (DMMO) for
      Lesser Toe Metatarsalgia.
AB  - BACKGROUND: As in all fields of surgery, advances in orthopaedic surgery develop
      toward less invasive surgical techniques. The advantages of smaller incisions
      include minimal soft tissue dissection allowing procedures to be performed as
      outpatient surgery. There is the assumption that this leads to a quicker recovery
      time permitting an earlier return to work. As with any new surgical technique,
      there is an associated learning curve. This study looked into the outcome of
      minimally invasive distal metatarsal metaphyseal osteotomy (DMMO) performed at a
      University Hospital. METHODS: Thirty patients underwent minimally invasive
      surgery for DMMO. There were 13 males and 17 females with an average age of 60
      years. More than one metatarsal osteotomy was done in all cases to facilitate the
      moulding of the metatarsal head to the correct alignment with full weight
      bearing. The outcome was measured with the Manchester-Oxford Foot Questionnaire
      (MOXFQ), patient-reported outcome (PRO), and visual analog scale (VAS) pain
      score. Minimum follow up was 1 year. RESULTS: At the final review, the average
      MOXFQ score was an excellent 31. Average improvement in VAS score was 3.5, which
      ranged from 10 to -7. The VAS was affected by 2 patients whose pain worsened
      after the operation. There were 4 complications, one each of nonunion, malunion,
      transfer metatarsalgia, and soft tissue ossification. CONCLUSION: The 3 most
      common complications of foot and ankle surgery are infection, wound dehiscence,
      and skin ulcer or blister. Intra-articular metatarsal osteotomies are commonly
      associated with stiffness due to scarring and consequently hammertoes. By
      reducing the soft tissue injury in minimally invasive surgery, these risks can be
      potentially minimized. Minimally invasive DMMO produced good patient
      satisfaction, functional improvement, and low complication rates in most cases.
      LEVEL OF EVIDENCE: Level IV, retrospective case series.

PMID- 26314304
TI  - Chemical and biological characterisation of Machaerium hirtum (Vell.) Stellfeld:
      absence of cytotoxicity and mutagenicity and possible chemopreventive potential.
AB  - Machaerium hirtum (Vell.) Stellfeld (M.hirtum) is a plant known as 'jacaranda
      bico-de-pato' whose bark is commonly used against diarrhea, cough and cancer. The
      aim of this study was to phytochemically characterise the hydroethanolic extract
      of this plant, investigate its antimutagenic activities using the Ames test and
      evaluate its effects on cell viability, genomic instability, gene expression and
      cell protection in human hepatocellular carcinoma cells (HepG2). Antimutagenic
      activity was assessed by simultaneous pre- and post-treatment with direct and
      indirect mutagens, such as 4-nitro-o-phenylenediamine (NPD), mitomycin C (MMC),
      benzo[a]pyrene (B[a]P) and aflatoxin B1 (AFB1), using the Ames test, cytokinesis
      blocking micronucleus and apoptosis assays. Only 3 of the 10 concentrations
      evaluated in the MTT assay were cytotoxic in HepG2 cells. Micronucleated or
      apoptotic cells were not observed with any of the tested concentrations, and
      there were no mutagenic effects in the bacterial system. However, the Nuclear
      Division Index and flow cytometry data showed a decrease in cell proliferation.
      The extract showed an inhibitory effect against direct (NPD) and indirect
      mutagens (B[a]P and AFB1). Furthermore, pre- and post-treated cells showed
      significant reduction in the number of apoptotic and micronucleated cells. This
      effect is not likely to be associated with the modulation of antioxidant genes,
      as shown by the RT-qPCR results. Six known flavonoids were identified in the
      hydroethanolic extract of Machaerium hirtum leaves, and their structures were
      elucidated by spectroscopic and spectrophotometric methods. The presence of the
      antioxidants apigenin and luteolin may explain these protective effects, because
      these components can inhibit the formation of reactive species and prevent
      apoptosis and DNA damage. In conclusion, the M.hirtum extract showed
      chemopreventive potential and was not hazardous at the tested concentrations in
      the experiments presented here. Moreover, this extract should be investigated
      further as a chemopreventive agent.

PMID- 26314306
TI  - Midwifery training needs identified when caring for women with female genital
      mutilation.

PMID- 26314305
TI  - Comparative Genomics Including the Early-Diverging Smut Fungus Ceraceosorus
      bombacis Reveals Signatures of Parallel Evolution within Plant and Animal
      Pathogens of Fungi and Oomycetes.
AB  - Ceraceosorus bombacis is an early-diverging lineage of smut fungi and a pathogen
      of cotton trees (Bombax ceiba). To study the evolutionary genomics of smut fungi
      in comparison with other fungal and oomycete pathogens, the genome of C. bombacis
      was sequenced and comparative genomic analyses were performed. The genome of
      26.09 Mb encodes for 8,024 proteins, of which 576 are putative-secreted effector
      proteins (PSEPs). Orthology analysis revealed 30 ortholog PSEPs among six
      Ustilaginomycotina genomes, the largest groups of which are lytic enzymes, such
      as aspartic peptidase and glycoside hydrolase. Positive selection analyses
      revealed the highest percentage of positively selected PSEPs in C. bombacis
      compared with other Ustilaginomycotina genomes. Metabolic pathway analyses
      revealed the absence of genes encoding for nitrite and nitrate reductase in the
      genome of the human skin pathogen Malassezia globosa, but these enzymes are
      present in the sequenced plant pathogens in smut fungi. Interestingly, these
      genes are also absent in cultivable oomycete animal pathogens, while nitrate
      reductase has been lost in cultivable oomycete plant pathogens. Similar patterns
      were also observed for obligate biotrophic and hemi-biotrophic fungal and
      oomycete pathogens. Furthermore, it was found that both fungal and oomycete
      animal pathogen genomes are lacking cutinases and pectinesterases. Overall, these
      findings highlight the parallel evolution of certain genomic traits, revealing
      potential common evolutionary trajectories among fungal and oomycete pathogens,
      shaping the pathogen genomes according to their lifestyle. 

PMID- 26314307
TI  - Current Neonatal Skin Care Practices in Four African Sites.
AB  - Data for this study on skin care practices and emollient use in four African
      sites were collected using in-depth interviews, focus-group discussions and
      observations. Respondents were mothers, grandmothers, fathers, health workers,
      birth attendants and people selling skin-care products. Analysis included content
      and framework analyses.Emollient use was a normative practice in all sites, with
      frequent application from an early age in most sites. There were variations in
      the type of emollients used, but reasons for use were similar and included
      improving the skin, keeping the baby warm, softening/strengthening the
      joints/bones, shaping the baby, ensuring flexibility and encouraging growth and
      weight gain. Factors that influenced emollient choice varied and included social
      pressure, cost, availability and deep-rooted traditional norms. Massage
      associated with application was strong and potentially damaging to the skin in
      some sites.Given the widespread use of emollients, the repeated exposure of
      newborns in the first month of life and the potential impact of emollients on
      mortality, trials such as those that have been conducted in Asia are needed in a
      range of African settings. 

PMID- 26314308
TI  - Safety and Efficacy of Low-osmolarity ORS vs. Modified Rehydration Solution for
      Malnourished Children for Treatment of Children with Severe Acute Malnutrition
      and Diarrhea: A Randomized Controlled Trial.
AB  - World Health Organization-recommended rehydration solution for malnourished
      children (ReSoMal) for rehydrating severe acute malnourished children is not
      available in India. In present study, 110 consecutive children aged 6-59 months
      with severely acute malnourishment and acute diarrhea were randomized to low
      osmolarity oral rehydration solution (ORS) (osmolarity: 245, sodium: 75) with
      added potassium (20 mmol/l) or modified ReSoMal (osmolarity: 300, sodium: 45). In
      all, 15.4% of modified ReSoMal group developed hyponatremia as compared with 1.9%
      in low-osmolarity ORS, but none developed severe hyponatremia or hypernatremia.
      Both groups had equal number of successful rehydration (52 each). Both types of
      ORS were effective in correcting hypokalemia and dehydration, but rehydration was
      achieved in shorter duration with modified ReSoMal.

PMID- 26314309
TI  - [Not Available].

PMID- 26314311
TI  - Dose-Response Effect of Sunlight on Vitamin D2 Production in Agaricus bisporus
      Mushrooms.
AB  - The dose response effect of UV-B irradiation from sunlight on vitamin D2 content
      of sliced Agaricus bisporus (white button mushroom) during the process of sun
      drying was investigated.Real-time UV-B and UV-A data were obtained using a high
      performance spectroradiometer. During the first hour of sunlight exposure, the
      vitamin D2 content of the mushrooms increased in a linear manner, with
      concentrations increasing from 0.1 MUg/g up to 3.9 +/- 0.8 MUg/g dry weight (DW).
      At the subsequent two measurements one and 3 h later, respectively, a plateau was
      reached. Two hours of additional exposure triggered a significant decline in
      vitamin D2 content. After just 15 min of sun exposure and an UV-B dose of 0.13
      J/cm(2), the vitamin D2 content increased significantly to 2.2 +/- 0.5 MUg/g DW
      (P < 0.0001), which is equivalent to 17.6 MUg (704 IU) vitamin D2 per 100 g of
      fresh mushrooms and comparable to levels found in fatty fish like the Atlantic
      salmon. 

PMID- 26314310
TI  - Structural Studies of AAV2 Rep68 Reveal a Partially Structured Linker and Compact
      Domain Conformation.
AB  - Adeno-associated virus (AAV) nonstructural proteins Rep78 and Rep68 carry out all
      DNA transactions that regulate the AAV life cycle. They share two multifunctional
      domains: an N-terminal origin binding/nicking domain (OBD) from the HUH
      superfamily and a SF3 helicase domain. A short linker of ~20 amino acids that is
      critical for oligomerization and function connects the two domains. Although X
      ray structures of the AAV5 OBD and AAV2 helicase domains have been determined,
      information about the full-length protein and linker conformation is not known.
      This article presents the solution structure of AAV2 Rep68 using small-angle X
      ray scattering (SAXS). We first determined the X-ray structures of the minimal
      AAV2 Rep68 OBD and of the OBD with the linker region. These X-ray structures
      reveal novel features that include a long C-terminal alpha-helix that protrudes
      from the core of the protein at a 45 degrees  angle and a partially structured
      linker. SAXS studies corroborate that the linker is not extended, and we show
      that a proline residue in the linker is critical for Rep68 oligomerization and
      function. SAXS-based rigid-body modeling of Rep68 confirms these observations,
      showing a compact arrangement of the two domains in which they acquire a
      conformation that positions key residues in all domains on one face of the
      protein, poised to interact with DNA. 

PMID- 26314312
TI  - Progesterone secretion by ovine granulosa cells: effects of nitric oxide and
      plane of nutrition.
AB  - The aim was to evaluate the effects of nutritional plane on in vitro progesterone
      (P4) secretion by granulosa (G) cells cultured in the presence or absence of
      effectors of the nitric oxide (NO) system. Ewes were randomly assigned into three
      nutritional groups: control (C), overfed (O; 2 * C), or underfed (U; 0.6 * C).
      Follicular development was induced by FSH injections. On day 15 of the estrous
      cycle, G cells were isolated and cultured with or without DETA-NONOate (NO
      donor), L-NAME (NO synthase [S] inhibitor), Arg and (or) LH for 8 h. DETA-NONOate
      decreased basal and LH-stimulated P4 secretion, and L-NAME increased basal P4
      secretion in all groups. In U, Arg decreased LH-stimulated P4 secretion. These
      data demonstrate that (i) plane of nutrition affects basal P4 secretion by G
      cells, (ii) the NO donor decreases, NOS inhibitor increases but Arg does not
      affect basal P4 secretion, and (iii) effects of Arg on LH-stimulated P4 secretion
      are affected by plane of nutrition in FSH-treated sheep. Thus, plane of nutrition
      affects G cell function, and the NO system is involved in the regulation of basal
      and LH-stimulated P4 secretion. The mechanism of the NO system effects on
      secretory activity of G cells remains to be elucidated. 

PMID- 26314313
TI  - beta1-adrenoceptor Arg389Gly polymorphism and heart disease: marching toward
      clinical practice integration.

PMID- 26314314
TI  - Death ligands and granulysin: mechanisms of tumor cell death induction and
      therapeutic opportunities.
AB  - The immune system plays a key role in cancer immune surveillance to control tumor
      development. The final goal is recognizing and killing transformed cells and
      consequently the elimination of the tumor. The main effector cell types exerting
      cytotoxicity against tumors are natural killer (NK) cells and cytotoxic T
      lymphocytes (CTLs). Although the mechanism of activation of NK cells and CTLs are
      quite different, both cell types share common antitumor effector mechanisms of
      cytotoxicity which lead to induction of cell death of tumor cells by apoptosis.
      Among these mechanisms are the death ligand- and granulysin-mediated cell deaths.
      In this review, we summarize the main concepts of these effector cytotoxic
      mechanisms against cancer cells, how NK cells and CTLs use them to control tumor
      development and the therapeutic approaches currently developed based on these
      molecules. 

PMID- 26314315
TI  - Black elderberry extract attenuates inflammation and metabolic dysfunction in
      diet-induced obese mice.
AB  - Dietary anthocyanins have been shown to reduce inflammation in animal models and
      may ameliorate obesity-related complications. Black elderberry is one of the
      richest sources of anthocyanins. We investigated the metabolic effects of
      anthocyanin-rich black elderberry extract (BEE) in a diet-induced obese C57BL/6J
      mouse model. Mice were fed either a low-fat diet (n 8), high-fat lard-based diet
      (HFD; n 16), HFD+0.25 % (w/w) BEE (0.25 %-BEE; n 16) or HFD+1.25 % BEE (1.25 %
      BEE; n 16) for 16 weeks. The 0.25 % BEE (0.034 % anthocyanin, w/w) and 1.25 % BEE
      (0.17 % anthocyanin, w/w) diets corresponded to estimated anthocyanin doses of 20
      40 mg and 100-200 mg per kg of body weight, respectively. After 16 weeks, both
      BEE groups had significantly lower liver weights, serum TAG, homoeostasis model
      assessment and serum monocyte chemoattractant protein-1 compared with HFD. The
      0.25 %-BEE also had lower serum insulin and TNFalpha compared with HFD. Hepatic
      fatty acid synthase mRNA was lower in both BEE groups, whereas PPARgamma2 mRNA
      and liver cholesterol were lower in 1.25 %-BEE, suggesting decreased hepatic
      lipid synthesis. Higher adipose PPARgamma mRNA, transforming growth factor beta
      mRNA and adipose tissue histology suggested a pro-fibrogenic phenotype that was
      less inflammatory in 1.25 %-BEE. Skeletal muscle mRNA expression of the myokine
      IL-6 was higher in 0.25 %-BEE relative to HFD. These results suggest that BEE may
      have improved some metabolic disturbances present in this mouse model of obesity
      by lowering serum TAG, inflammatory markers and insulin resistance. 

PMID- 26314316
TI  - Successful extracorporeal membrane oxygenation therapy as a bridge to sequential
      bilateral lung transplantation for a patient after severe paraquat poisoning.
AB  - CONTEXT: Paraquat is a widely used herbicide that can cause severe to fatal
      poisoning in humans. The irreversible and rapid progression of pulmonary fibrosis
      associated with respiratory failure is the main cause of death in the later
      stages of poisoning. There are infrequent reports of successful lung transplants
      for cases of severe paraquat poisoning. We expect that this successful case will
      provide a reference for other patients in similar circumstances. CASE DETAILS: A
      24-year-old female was sent to the hospital approximately 2 hours after ingesting
      50 ml of paraquat. She experienced rapidly aggravated pulmonary fibrosis and
      severe respiratory failure. On the 34th day after ingestion, she underwent
      intubation and invasive mechanical ventilation. The patient was evaluated for
      lung transplantation, and veno-venous extracorporeal membrane oxygenation (ECMO)
      was established as a bridge to lung transplantation on the 44th day. On the 56th
      day, she successfully underwent a bilateral sequential lung transplantation.
      Through respiratory and physical rehabilitation and nutrition support, the
      patient was weaned from mechanical ventilation and extubated on the 66th day. On
      the 80th day, she was discharged. During the 1-year follow-up, the patient was
      found to be in good condition, and her pulmonary function improved gradually.
      CONCLUSION: We suggest that lung transplantation may be an effective treatment in
      the end stages of paraquat-induced pulmonary fibrosis and consequential
      respiratory failure. For patients experiencing a rapid progression to a critical
      condition in whom lung transplantation cannot be performed immediately (e.g.,
      while awaiting a viable donor or toxicant clearance), ECMO should be a viable
      bridge to lung transplantation.

PMID- 26314317
TI  - Targets and outcomes.

PMID- 26314318
TI  - ENT entry requirements for UK armed forces.
AB  - BACKGROUND: Minimum health requirements exist for entry into the UK armed forces.
      Both pre-existing and iatrogenic ENT conditions may impact on an individual's
      medical fitness and their ability to enter the forces. METHODS: The relevant
      literature was examined and military otolaryngology advisors were interviewed in
      order to define the ENT-specific conditions that restrict an individual joining
      the armed forces. RESULTS: The ENT diseases and disabilities that inhibit an
      individual's ability to join the forces are described. Treatments that may
      facilitate or restrict recruitment are also discussed. CONCLUSION: Members of the
      armed forces operate in arduous environments and are required to pass a screening
      medical assessment before joining. Personnel may be isolated away from specialist
      care and therefore cannot be dependent on specialist devices or medicines. This
      paper aims to arm ENT specialists with occupational knowledge to enable them to
      correctly counsel patients and offer appropriate treatment.

PMID- 26314319
TI  - Comparison of quality of life outcomes following different mastoid surgery
      techniques.
AB  - BACKGROUND: Mastoid surgery carried out to treat chronic otitis media can lead to
      improvement in objective and subjective measures post-operatively. This study
      investigated the subjective change in quality of life using the Glasgow Benefit
      Inventory relative to the type of mastoid surgery undertaken. METHOD: A
      retrospective multicentre postal survey of 157 patients who underwent mastoid
      surgery from 2008 to 2012 was conducted. RESULTS: Eighty-three questionnaire
      responses were received from patients who underwent surgery at one of three
      different hospitals (a response rate of 53 per cent). Fifty-seven per cent of
      patients had a Glasgow Benefit Inventory score of 0, indicating no change in
      quality of life post-operatively. Thirty-five per cent scored over 50, indicating
      significant improvement. The only significant difference found was that women
      fared worse after surgery than men. CONCLUSION: The choice of mastoid surgery
      technique should be determined by clinical need and surgeon preference. There is
      no improvement in quality of life for most patients following mastoid surgery.

PMID- 26314320
TI  - Can computed tomography and magnetic resonance imaging differentiate between
      malignant pathology and osteomyelitis in the central skull base?
AB  - BACKGROUND: Central skull base osteomyelitis is clinically difficult to
      distinguish from malignancy. METHOD: The computed tomography and magnetic
      resonance imaging scans of six patients with central skull base osteomyelitis
      were compared with scans from patients with a range of skull base conditions.
      RESULTS AND CONCLUSION: Computed tomography scans of central skull base
      osteomyelitis show much less bony destruction relative to the magnetic resonance
      imaging changes, whereas malignancy cases were associated with similar bony
      destruction on computed tomography and magnetic resonance imaging. In magnetic
      resonance imaging scans, it was possible to confirm previous findings of clival
      hypointensity on T1-weighted images relative to normal fatty marrow. In addition,
      there were signs of pre- and para-clival soft tissue infiltration, with the
      obliteration of normal fat planes and frank soft tissue masses in all six central
      skull base osteomyelitis patients. Signal intensity on T2-weighted images of the
      clivus was high in five central skull base osteomyelitis patients. With
      intravenous contrast, fascial plane anatomy appeared restored in central skull
      base osteomyelitis cases, almost in keeping with that of non-involved areas. This
      was not a feature in any of the malignant conditions.

PMID- 26314321
TI  - Myringoplasty outcomes in the UK.
AB  - OBJECTIVES: To determine the outcome of myringoplasty as undertaken by ENT
      surgeons in the UK, and to assess the current systems available for providing
      national outcome data. METHODS: A prospective national multicentre audit was
      conducted involving multiple hospitals throughout the UK. Participants consisted
      of ENT surgeons practising in the UK. RESULTS: Data were prospectively collected
      over a three-year period between 1 March 2006 and 1 March 2009 using the web
      based Common Otology Database. In total, 33 surgeons provided valid and complete
      data for 495 procedures. The overall closure rate for myringoplasty was 89.5 per
      cent. The average hearing gain for successful primary myringoplasties was 9.14 dB
      (standard deviation = 10.62). The Common Otology Database provided an effective
      platform for capturing outcome data. CONCLUSION: Myringoplasty is a safe and
      effective procedure in the UK. With the introduction of revalidation by the
      General Medical Council, participation in national audits will be mandatory in
      the future. This study demonstrates that a web-based audit tool would be suitable
      for performing such audits.

PMID- 26314322
TI  - Changing indications for paediatric tracheostomy and the role of a
      multidisciplinary tracheostomy clinic.
AB  - OBJECTIVE: This paper presents our experience of managing children with a
      tracheostomy in a multidisciplinary team clinic consisting of an ENT consultant,
      paediatric respiratory consultant, a nurse specialist, and speech and language
      therapist. METHOD: A retrospective case note review was conducted of all children
      seen in the multidisciplinary team tracheostomy clinic (at a tertiary paediatric
      hospital) between February 2009 and September 2014. RESULTS: Ninety-seven
      patients were examined. The most common indications for tracheostomy were: lower
      airway and respiratory problems (66 per cent), upper airway obstruction (64 per
      cent), and neurodevelopmental problems (60.8 per cent). CONCLUSION: Children with
      a tracheostomy are a diverse group of patients. The most common indications for
      paediatric tracheostomy have changed from infective causes to airway obstruction
      and anomalies, long-term ventilation requirement, and underlying neuromuscular or
      respiratory problems. Our unified approach empowers the carers and patient, as a
      home management plan, long-term plan and goals are generated at the end of each
      appointment.

PMID- 26314323
TI  - Tailed Palva flap in the subperiosteal pocket technique for cochlear
      implantation.
AB  - BACKGROUND: In recent years, the subperiosteal pocket technique has become
      popular for minimal access cochlear implantation. Many incision techniques have
      been described in cochlear implantation. OBJECTIVE: This study aimed to
      demonstrate the safety and reliability of a new periosteal incision, called
      tailed Palva incision, in cochlear implantation. METHODS: A total of 280 patients
      who underwent cochlear implantation with the subperiosteal pocket technique
      between June 2008 and January 2013 were included in the study. RESULTS: The
      patients were followed up for between 11 and 74 months (mean +/- standard
      deviation = 34 +/- 19 months). No intracranial complications were seen during or
      after the operations. Additionally, there was no migration of the receiver
      stimulator. Revision surgery was performed in eight patients (3 per cent), one of
      whom (0.4 per cent) had local flap failure and infection. CONCLUSION: This study
      shows that the tailed Palva incision facilitates easy insertion of the implant
      and, by creating a one-way obscured pocket, this technique also enhances
      stabilisation of the receiver-stimulator, thereby avoiding anterior migration.

PMID- 26314324
TI  - Intra-operative skull X-ray for misdirection of the cochlear implant array into
      the vestibular labyrinth.
AB  - OBJECTIVES: This paper reports five cases of aberrant cochlear implant electrode
      array insertion into the vestibular labyrinth. A review of the literature was
      conducted in order to clarify reasonable preventive and detection strategies and
      endorse the routine use of intra-operative plain skull X-ray. METHODS: The study
      entailed a clinical case series and literature review. The setting was a tertiary
      academic referral centre. The following data were evaluated: pre-operative
      temporal bone computed tomography, operative reports, intra-operative imaging,
      neural response telemetry/imaging and post-operative imaging. RESULTS: There were
      no consistent pre-operative risk factors found on computed tomography scans and
      no reliable intra-operative signs of electrode array misdirection. All
      misdirections in our case series, and those in the literature, were easily
      detectable on intra-operative plain film X-ray. CONCLUSION: These reported cases
      demonstrate implant misdirection without the surgeon's awareness. Aberrant
      insertion cannot be anticipated, and neural response telemetry/imaging is not a
      reliable indicator of misdirection. Routine intra-operative anteroposterior plain
      X-ray of the head is a reliable indicator of misdirection, and is fast and
      relatively inexpensive.

PMID- 26314325
TI  - A case of subglottic tumour presenting with type 2 respiratory failure.
AB  - BACKGROUND: Although type 2 respiratory failure is a plausible late presentation
      for laryngeal tumours, very little published literature is available to support
      this theory. METHODS: This paper describes the unusual presentation of a
      subglottic tumour with uncompensated type 2 respiratory failure. RESULTS: The
      patient was initially managed with biphasic positive airway pressure as a
      bridging measure while awaiting intensive care treatment and to provide
      sufficient time to arrange a surgical tracheostomy. CONCLUSION: This case
      highlights the importance of clinical suspicion towards subglottic tumours in
      patients presenting with type 2 respiratory failure. The positive outcome
      indicates that biphasic positive airway pressure is a potential bridging therapy
      for upper airway obstruction and a safe and stable treatment option for patients
      in respiratory distress.

PMID- 26314326
TI  - Resveratrol enhanced anticancer effects of cisplatin on non-small cell lung
      cancer cell lines by inducing mitochondrial dysfunction and cell apoptosis.
AB  - Resveratrol is a plant-derived natural compound which possesses potential
      anticancer properties. However, there are scarce reports on its anticancer
      effects in non-small cell lung cancer and its auxiliary function on the
      anticancer effects of cisplatin. In the present study, we investigated the
      effects of resveratrol on the cell viability and apoptosis in human non-small
      cell lung cancer H838 and H520 cell lines. It has been found that resveratrol
      inhibited the proliferation of H838 and H520 cells in a dose- and time-dependent
      manner, and apoptosis was increased in cells treated with resveratrol which was
      associated with the depolarization of mitochondrial membrane potential, release
      of cytochrome c from mitochondria to cytosol, and abnormal expression of Bcl-2
      and Bax proteins. Above all, resveratrol enhanced the effects of cisplatin on
      inhibition of cancer cell proliferation, induction of cell apoptosis,
      depolarization of mitochondrial membrane potential, release of cytochrome c and
      regulation on expression of Bcl-2 and Bax. Results from the present study
      demonstrated that resveratrol exhibited its anticancer effects on non-small cell
      lung cancer H838 and H520 cell lines, and enhanced the antitumor effects of
      cisplatin by regulating the mitochondrial apoptotic pathway. These results have
      put forward the rationale for further basic research and preclinical
      investigation on the anticancer effects of resveratrol against human non-small
      cell lung cancer.

PMID- 26314327
TI  - Incorporating nanoporous polyaniline into layer-by-layer ionic liquid-carbon
      nanotube-graphene paper: towards freestanding flexible electrodes with improved
      supercapacitive performance.
AB  - The growing demand for lightweight and flexible supercapacitor devices
      necessitates innovation in electrode materials and electrode configuration. We
      have developed a new type of three-dimensional (3D) flexible nanohybrid electrode
      by incorporating nanoporous polyaniline (PANI) into layer-by-layer ionic liquid
      (IL) functionalized carbon nanotube (CNT)-graphene paper (GP), and explored its
      practical application as a freestanding flexible electrode in a supercapacitor.
      Our results have demonstrated that the surface modification of graphene
      nanosheets and CNTs by hydrophilic IL molecules makes graphene and CNTs well
      dispersed in aqueous solution, and also improves the hydrophility of the
      assembled graphene-based paper. Furthermore, the integration of highly conductive
      one-dimensional (1D) CNTs with two-dimensional (2D) graphene nanosheets leads to
      3D sandwich-structured nanohybrid paper with abundant interconnected pores, which
      is preferred for fast mass and electron transport kinetics. For in situ
      electropolymerization of PANI on paper electrodes, the IL functionalized CNT-GP
      (IL-CNT-GP) offers large surface area and interlayer spacing and the unique pi
      surface of graphene and CNTs for efficient and stable loading of PANI. A key
      finding is that the structural integration of multiple components in this 3D
      freestanding flexible sheet electrode gives rise to a synergic effect, leading to
      a high capacitance of 725.6 F g(-1) at a current density of 1 A g(-1) and good
      cycling stability by retaining 90% of the initial specific capacitance after 5000
      cycles. 

PMID- 26314333
TI  - Characterization of WWP1 protein expression in skeletal muscle of muscular
      dystrophy chickens.
AB  - A missense mutation in the gene encoding WWP1 was identified as the most
      promising candidate responsible for chicken muscular dystrophy (MD) by genetic
      linkage analysis. WWP1 is a HECT-type E3 ubiquitin protein ligase composed of 922
      amino acids, which contains 4 tandem WW domains that interact with the proline
      rich peptide motifs of target proteins. The missense mutation changes arginine
      441 that is located in the centre of the WW domains into glutamine (R441Q), which
      potentially affects the function of the WWP1 protein. Here, we show that WWP1 is
      detected as ~130-kDa protein that localizes to various structures, such as the
      plasma membrane (sarcolemma), sarcoplasmic reticulum, mitochondria and nucleus,
      in normal chicken skeletal muscle. However, in MD chickens, the mutant WWP1
      protein was markedly degraded and was absent in the sarcolemma. These changes
      were also observed in the muscles of chickens in early pre-pathological states.
      Moreover, in vitro expression analysis showed significant degradation of mutant,
      but not wild-type WWP1, specifically in myogenic cells. Altogether, our data
      revealed that the R441Q missense mutation in the WWP1 protein causes degradation
      and loss of the sarcolemmal localization of WWP1, which may play a role in the
      pathogenesis of chicken MD. 

PMID- 26314335
TI  - Optical spectroscopy coupled with mass spectrometry methods.

PMID- 26314334
TI  - Lysine 206 in Arabidopsis phytochrome A is the major site for ubiquitin-dependent
      protein degradation.
AB  - Phytochrome A (phyA) is a light labile phytochrome that mediates plant
      development under red/far-red light condition. Degradation of phyA is initiated
      by red light-induced phyA-ubiquitin conjugation through the 26S proteasome
      pathway. The N-terminal of phyA is known to be important in phyA degradation. To
      determine the specific lysine residues in the N-terminal domain of phyA involved
      in light-induced ubiquitination and protein degradation, we aligned the amino
      acid sequence of the N-terminal domain of Arabidopsis phyA with those of phyA
      from other plant species. Based on the alignment results, phytochrome over
      expressing Arabidopsis plants were generated. In particular, wild-type and mutant
      (substitutions of conserved lysines by arginines) phytochromes fused with GFP
      were expressed in phyA(-)211 Arabidopsis plants. Degradation kinetics of over
      expressed phyA proteins revealed that degradation of the K206R phyA mutant
      protein was delayed. Delayed phyA degradation of the K206R phyA mutant protein
      resulted in reduction of red-light-induced phyA-ubiquitin conjugation.
      Furthermore, seedlings expressing the K206R phyA mutant protein showed an
      enhanced phyA response under far-red light, resulting in inhibition of hypocotyl
      elongation as well as cotyledon opening. Together, these results suggest that
      lysine 206 is the main lysine for rapid ubiquitination and protein degradation of
      Arabidopsis phytochrome A. 

PMID- 26314336
TI  - Copper-catalyzed oxidative decarboxylative C-H arylation of benzoxazoles with 2
      nitrobenzoic acids.
AB  - A copper-catalyzed oxidative decarboxylative coupling of benzoxazoles with 2
      nitrobenzoic acids was developed. This methodology favors electron-rich
      benzoxazoles and electron-deficient benzoic acids and enables the preparation of
      a variety of arylated benzoxazoles in good yields. The trends in product yields
      suggest a delicate balance between the decarboxylation and C-H arylation steps. 

PMID- 26314337
TI  - FCGR2A, FCGR3A, FCGR3B polymorphisms and susceptibility to rheumatoid arthritis:
      a meta-analysis.
AB  - OBJECTIVES: The aim of this study is to explore whether Fc gamma receptor (FCGR)
      polymorphisms are associated with the susceptibility to rheumatoid arthritis
      (RA). METHODS: We conducted a meta-analysis on the association between FCGR2A
      H131R (rs1801274), FCGR3A F158V (rs396991), and FCGR3B NA1/NA2 polymorphisms and
      RA susceptibility. RESULTS: A total of seventeen studies reported in fourteen
      articles (4,418 patients with RA and 3,560 controls) were considered in our meta
      analysis. In all of the study subjects, meta-analysis indicated an association
      between RA and FCGR2A R allele (OR=0.877, 95% CI=0.792-0.971, p=0.011).
      Stratification by ethnicity indicated an association between FCGR2A R allele and
      RA in Europeans (OR=0.816, 95% CI=0.687-0.968, p=0.020), but not in East Asians
      (OR=0.900, 95% CI=0.778-1.040, p=0.154). Meta-analysis revealed an association
      between RA and FCGR3A VV vs. FF genotype in all the study subjects (OR=1.210, 95%
      CI=1.067-1.479, p=0.006). Stratification by ethnicity indicated an association
      between FCGR3A VV genotype and RA compared toFF genotype in Europeans (OR=1.350,
      95% CI=1.107-1.646, p=0.003), but not in East Asians and South Asians. No
      association was observed between RA and FCGR3B polymorphisms on performing the
      meta-analysis. CONCLUSIONS: Although no relationship was found between the FCGR3B
      polymorphism and RA susceptibility, FCGR2A and FCGR3A polymorphisms were found to
      be associated with RA in Europeans, but not in Asians.

PMID- 26314338
TI  - Thinking about thinking: changes in first-year medical students' metacognition
      and its relation to performance.
AB  - BACKGROUND: Studies have shown the importance of metacognition in medical
      education. Metacognitive skills consist of two dimensions: knowledge of
      metacognition and regulation of metacognition. AIM: This study hypothesizes that
      the knowledge and regulation of metacognition is significantly different at the
      beginning and end of the academic year, and a correlation exists between the two
      dimensions of metacognitive skills with academic performance. METHODS: The
      Metacognitive Skills Inventory comprising 52 Likert-scale items was administered
      to 159 first-year medical students at the University of Malaya. Students' year
      end results were used to measure their academic performance. RESULTS: A paired
      sample t-test indicated no significant difference for knowledge of metacognition
      at the beginning and end of the academic year. A paired sample t-test revealed
      significant difference for regulation of metacognition at the beginning and end
      of the academic year. A very strong correlation was found between the two
      dimensions of metacognition. The correlation between knowledge and regulation of
      metacognition with students' academic result was moderate. CONCLUSIONS: The
      improvement in students' metacognitive regulation and the moderate correlation
      between knowledge and regulation of metacognition with academic performance at
      the end of the academic year indicate the probable positive influence of the
      teaching and learning activities in the medical program.

PMID- 26314339
TI  - Identification of A Novel Small-Molecule Binding Site of the Fat Mass and Obesity
      Associated Protein (FTO).
AB  - N-(5-Chloro-2,4-dihydroxyphenyl)-1-phenylcyclobutanecarboxamide (N-CDPCB, 1a) is
      found to be an inhibitor of the fat mass and obesity associated protein (FTO).
      The crystal structure of human FTO with 1a reveals a novel binding site for the
      FTO inhibitor and defines the molecular basis for recognition by FTO of the
      inhibitor. The identification of the new binding site offers new opportunities
      for further development of selective and potent inhibitors of FTO, which is
      expected to provide information concerning novel therapeutic targets for
      treatment of obesity or obesity-associated diseases. 

PMID- 26314340
TI  - The potential anti-proliferative effect of beta-sitosterol on human mast cell
      line-1 cells.
AB  - Thymic stromal lymphopoietin (TSLP) was reported to induce mast cell
      proliferation and aggravate allergic reactions through activation of mouse double
      minute 2 (MDM2). We aimed to ascertain that beta-sitosterol (SI), which is one of
      the several phytosterols found mostly in foods, would regulate TSLP-induced mast
      cell proliferation. The results showed that SI significantly decreased the
      proliferation of human mast cell line (HMC-1) cells promoted by TSLP. SI
      significantly decreased the mRNA expression of Ki-67 in the TSLP-treated HMC-1
      cells. SI significantly suppressed the production and mRNA expression of
      interleukin-13 in the TSLP-treated HMC-1 cells. Furthermore, SI downregulated the
      expression of MDM2 and phosphorylation of STAT6, whereas it upregulated the
      expression of p53, activation of caspase-3, and cleavage of poly ADP-ribose
      polymerase in the TSLP-treated HMC-1 cells. Results of this study suggest that SI
      may be a potential therapeutic agent for mast cell-mediated allergic diseases. 

PMID- 26314341
TI  - Association between PK/PD-involved gene polymorphisms and carbamazepine
      individualized therapy.
AB  - AIM: To evaluate the association between the major genetic variants involved in
      the pharmacokinetic/pharmacodynamic (PK/PD) properties of carbamazepine (CBZ) and
      its maintenance doses and concentrations. PATIENTS & METHODS: The genotypes of
      166 patients receiving CBZ monotherapy were detected using high-resolution
      melting curve (HRM) and TaqMan methods. RESULTS: Both univariate and multiple
      regression analyses revealed that carriers of the SCN1A IVS5-91G>A or EPHX1
      c.337T>C allele tended to require a higher CBZ dose and a lower CBZ natural
      logarithmic concentration-dose ratio (lnCDR) than noncarriers (p < 0.05).
      Furthermore, two interactions between these genes were associated with the lnCDR
      and the maintenance dosage of CBZ, respectively. CONCLUSION: SCN1A IVS5-91G>A
      gene polymorphism is potential genetic biomarker associated with the PK of CBZ.

PMID- 26314342
TI  - Experimental soil warming and cooling alters the partitioning of recent
      assimilates: evidence from a (14)C-labelling study at the alpine treeline.
AB  - Despite concerns about climate change effects on ecosystems functioning, little
      is known on how plant assimilate partitioning changes with temperature.
      Particularly, large temperature effects might occur in cold ecosystems where
      critical processes are at their temperature limit. In this study, we tested
      temperature effects on carbon (C) assimilate partitioning in a field experiment
      at the alpine treeline. We warmed and cooled soils of microcosms planted with
      Pinus mugo or Leucanthemopsis alpina, achieving daily mean soil temperatures (3
      10 cm depth) around 5.8, 12.7 and 19.2  degrees C in cooled, control and warmed
      soils. We pulse-labelled these systems with (14)CO2 for one photoperiod and
      traced (14)C over the successive 4 days. Plant net (14)C uptake increased
      steadily with soil temperature. However, (14)C amounts in fungal hyphae, soil
      microbial biomass, soil organic matter, and soil respiration showed a non-linear
      response to temperature. This non-linear pattern was particularly pronounced in
      P. mugo, with five times higher (14)C activities in cooled compared to control
      soils, but no difference between warmed and control soil. Autoradiographic
      analysis of the spatial distribution of (14)C in soils indicated that temperature
      effects on the vertical label distribution within soils depended on plant
      species. Our results show that plant growth, in particular root metabolism, is
      limited by low soil temperature. As a consequence, positive temperature effects
      on net C uptake may not be paralleled by similar changes in rhizodeposition. This
      has important implications for predictions of soil C storage, because
      rhizodeposits and plant biomass vary strongly in their residence times.

PMID- 26314343
TI  - Starting with a handicap: effects of asynchronous hatching on growth rate,
      oxidative stress and telomere dynamics in free-living great tits.
AB  - A trade-off between resource investment into growth rate and body self
      maintenance is likely to occur, but the underlying molecular mediators of such a
      trade-off remain to be determined. In many altricial birds, hatching asynchrony
      creates a sibling competitive hierarchy within the brood, with first-hatched
      nestlings enjoying substantial advantages compared to last-hatched nestlings. We
      used this opportunity to test for a trade-off between growth and self-maintenance
      processes (oxidative stress, telomere erosion) in great tit nestlings, since
      resource availability and allocation are likely to differ between first-hatched
      and last-hatched nestlings. We found that despite their starting competitive
      handicap (i.e. being smaller/lighter before day 16), last-hatched nestlings
      exhibited growth rate and mass/size at fledging similar to first-hatched ones.
      However, last-hatched nestlings suffered more in terms of oxidative stress, and
      ended growth with shorter telomeres than first-hatched ones. Interestingly,
      growth rate was positively related to plasma antioxidant capacity and early life
      telomere length (i.e. at 7 days old), but among last-hatched nestlings, those
      exhibiting the faster body size growth were also those exhibiting the greatest
      telomere erosion. Last-hatched nestlings exhibited elevated levels of plasma
      testosterone (T), but only at day 7. T levels were positively associated with
      oxidative damage levels and plasma antioxidant capacity, the latter being only
      significant for first-hatched nestlings. Our results suggest that last-hatched
      nestlings present a specific trade-off between growth rate and self-maintenance
      processes, which is possibly driven by their need to compete with their older
      siblings and potentially mediated by elevated levels of T.

PMID- 26314344
TI  - Bio-optic characterization of Discosphaera tubifer bloom occurs in an overcrowded
      fishing harbour at Veraval, India.
AB  - Discosphaera tubifer, a coccolithophore has been first time reported as a bloom
      forming organism from an over-crowded fishing harbour at Veraval, west coast of
      India. Physiochemical and optical parameters were measured following standard
      protocols. Average concentration of inorganic nutrients, such as NO2-N (17.26 +/-
      2.92 MUM), NO3-N (643.80 +/- 215.99 MUM), PO4-P (74.10 +/- 26.52 MUM) and SiO3-Si
      (137.66 +/- 25.83 MUM) were recorded as very high at Veraval port as compared to
      other coastal stations i.e., 1.48 +/- 0.66, 49.16 +/- 13.73, 10.03 +/- 5.31 and
      96.23 +/- 22.74 MUM, respectively. The pH and salinity (0/00) were observed to be
      low (7.80 +/- 0.15 and 28.00 +/- 4.54 0/00) as compared to coastal seawaters
      (8.34 +/- 0.06 and 33.24 +/- 2.32 0/00). Scanning electron microscopy (SEM) and
      spectral signature (absorbance and reflectance) study revealed that the bloom
      forming organism was D. tubifer. High-performance liquid chromatography (HPLC)
      study detected that chlorophyllide-a represent nearly 47.53 % of total pigment
      composition followed by chlorophyll c2 (27.40 %) and chlorophyll c3 (14.25 %).
      Four prominent absorption peaks were observed within 350 to 700 nm. The first
      peak was very wide and ranged from 350 to 530 nm and the rest of the three peaks
      ranged from 550 to 590, 590 to 650 and 650 to 690 nm, respectively. In case of
      reflection, three peaks appeared between 550 and 590, 590 and 630 and 630 and 670
      nm. Nearly 100 % reflection was observed after 720 nm. The eutrophic condition of
      the port water along with low salinity and low pH might be the reason for D.
      tubifer bloom formation. This species-specific spectral signature of the D.
      tubifer bloom may be helpful for developing algorithm of remote sensing data
      analysis.

PMID- 26314345
TI  - Environmental waters as a source of antibiotic-resistant Enterococcus species in
      Belgrade, Serbia.
AB  - Despite the number of studies on antibiotic-resistant enterococci from Serbian
      clinical settings, there are no data about environmental contamination with these
      bacteria. Thus, this study investigated the prevalence of antibiotic-resistant
      enterococci in Belgrade, Serbia. Enterococcus species collected from ten surface
      water sites, including a lake, two major river systems, and springs, were tested.
      Among enterococci, we found single (21.7 %), double (17.4 %), and multiple
      antibiotic resistance patterns (56.3 %). Vancomycin-resistant strains were not
      found, indicating that their abundance in Belgrade is tightly linked to clinical
      settings. The multiple drug-resistant strains Enterococcus faecalis, Enterococcus
      faecium, and Enterococcus mundtii were frequently detected in the lake during the
      swimming season and in the rivers near industrial zones. We confirmed the
      presence of ermB, ermC, ant(6)-Ia, tetM, and tetL and mutations in gyrA genes.
      The phylogenetic analysis of 16S rRNA gene of E. faecium isolates that harbor esp
      gene classified them into two groups based on high-bootstraps scores in the tree
      analysis. Pulsed-field gel electrophoresis analysis of antibiotic-resistant
      enterococci revealed genomic similarity ranging from 75 to 100 %. This study
      indicates the importance of anthropogenic impact to the spread of antibiotic
      resistant enterococci in environmental waters of Belgrade, Serbia.

PMID- 26314346
TI  - GIS methods for sustainable stormwater harvesting and storage using remote
      sensing for land cover data - location assessment.
AB  - Identification of potential sites for rainwater harvesting (RWH) is an important
      step toward maximizing water availability and land productivity in arid semiarid
      regions. Characterised as a "water scarce" country, Egypt has limited fresh water
      supplies, and is expected to suffer from water stress by the year 2030.
      Therefore, it is important to develop any means available to supply water and
      maintain human habitability in a sustainable manner. Practiced or simply
      indispensable in many countries around the world, rainwater harvesting (RWH)
      promotes a sustainable and efficient manner of exploiting water resources. In the
      present study, suitable areas for sustainable stormwater harvesting and storage
      in Egypt were identified using remote sensing for land cover data - location
      assessment linked to a decision support system (DSS). The DSS took into
      consideration a combination of thematic layers such as rainfall surplus, slope,
      potential runoff coefficient (PRC), land cover/use, and soil texture. Taking into
      account five thematic layers, the spatial extents of RWH suitability areas were
      identified by an analytical hierarchy process (AHP). The model generated a RWH
      map with five categories of suitability: excellent, good, moderate, poor and
      unsuitable. The spatial distribution of these categories in the area investigated
      was such that 4.8% (47910 km(2)) and 14% (139739 km(2)) of the study area was
      classified as excellent or good in terms of RWH, respectively, while 30.1%
      (300439 km(2)), 47.6% (474116 km(2)) and 3.5% (34935 km(2)) of the area were
      classified as moderate, unsuitable and poor, respectively. Most of the areas with
      excellent to good suitability had slopes of between 2% and 8% and were
      intensively cultivated areas. The major soil type in the excellent suitability
      areas was loam, while rainfall ranged from 100 to 200 mm yr(-1). The use of a
      number of RWH sites in the excellent areas is recommended to ensure successful
      implementation of RWH systems. 

PMID- 26314347
TI  - Does clinical protection persist after food allergen oral immunotherapy?

PMID- 26314348
TI  - [Intensive care treatment of patients with left ventricular assist devices].
AB  - Apart from heart transplantation, implantation of a left ventricular assist
      device (LVAD) is the only established surgical treatment for therapy-refractory
      terminal left heart failure, The specific intensive care unit (ICU) management of
      these patients depends on the reason for the ICU admission and requires
      understanding of the characteristic hemodynamics of non-pulsatile LVADs as well
      as of the inherent problems. Knowledge about the specific features in hemodynamic
      monitoring, understanding of pump characteristics, management of anticoagulation
      and hemostasis and the handling of problems, such as right heart failure, aortic
      valve insufficiency and infections is essential. The management of unconscious
      LVAD patients can be challenging. It requires a sophisticated transthoracic and
      transesophageal echocardiography (TTE/TEE) examination, targeted laboratory
      diagnostics and consideration of possible alternative diagnoses. Professional
      interdisciplinary cooperation and exchange of current knowledge is crucial. 

PMID- 26314349
TI  - A Comparative, Prospective and Randomized Evaluation of Roux-en-Y Gastric Bypass
      With and Without the Silastic Ring: A 2-Year Follow Up Preliminary Report on
      Weight Loss and Quality of Life.
AB  - BACKGROUND: Currently, Roux-en-Y gastric bypass (RYGB) is one of the most widely
      used bariatric surgeries. Banding the pouch forms a banded gastric bypass
      operation, an accepted and frequently used variant. Placing a silastic ring
      around the pouch to band the gastric bypass operation increases the restriction
      mechanism. However, the ubiquitous use of the banded gastric bypass remains
      controversial. One of the controversies is the effect of the silastic ring on
      patients' perception of their well being after surgery because of the frequency
      of vomiting. A prospective, blindly randomized, comparative trial was undertaken
      to resolve this controversy. METHOD: Four hundred subjects scheduled for gastric
      bypass surgery were randomized into two arms of the trial, 200 with a silastic
      ring (WR) and 200 without (NR). After 2-year follow-up, the variables associated
      with the scores of Bariatric Analysis and Reporting Outcome System (BAROS) were
      analyzed. RESULTS: The initial median weight (125 kg), BMI (47), and age (36
      years) were the same in both the NR and WR groups. The median excess weight loss,
      weight regain, and incidence of vomiting were 71, 10.5, and 7.75%, respectively,
      in the NR group vs. 75.4 and 1.1, and 24.4% in the WR group. The mean QOL score
      was 79% in the NR group vs. 80% in the WR group. CONCLUSION: After 2-year follow
      up, silastic ring placement in the RYGB resulted in greater weight loss and
      weight stability and a threefold greater incidence of vomiting. There was no
      difference in the scores in the quality of life analysis.

PMID- 26314350
TI  - Laparoscopic Adjustable Gastric Banding Revisions in Singapore: a 10-Year
      Experience.
AB  - BACKGROUND: Bariatric surgery is increasingly being carried out and revisional
      procedures have also risen in concert. A review of the complications and
      revisions might elucidate technical and patient factors that influence the
      outcomes of bariatric surgeries in Asian patients. The objective of this study is
      to review the safety and efficacy of revisional bariatric surgery in a single
      center in Singapore over a 10-year period. METHODS: The setting of this study is
      a single public hospital with a multidisciplinary bariatric service including a
      weight management center, specialized endocrinology services, and bariatric
      surgical team. Participants were selected for surgery based on body mass index
      (BMI) and comorbidities. All patients underwent primary laparoscopic adjustable
      gastric banding (LAGB). Patients were then analyzed according to the types of
      revisional surgeries. The primary outcome was the type of complications and
      revisional surgeries. Secondary outcomes include short-term excess weight loss
      and further complications. RESULTS: A total of 365 patients were analyzed. 9.6%
      had a secondary procedure. In particular, two groups of complications required
      revisional surgery: failure of sustained weight loss and complications related to
      the LAGB insertion and use. Revisional surgeries had equivalent major
      complication rates (5.7%) compared to primary bariatric surgeries (6.8%).
      Revisional surgeries such as revisional LAGB (4.9 +/- 9.8 kg), laparoscopic
      sleeve gastrectomy (LSG; 6.9 +/- 21.0 kg), Roux-en-Y gastric bypass (RYGB; 4.6 +/
      13.0 kg), and bilio-pancreatic diversion (BPD; 3.5 +/- 6.3 kg) had modest weight
      loss compared to primary weight loss (12.7 +/- 9.5 kg). Primary LAGB had a
      greater percentage excess weight loss in the first and second years post-surgery
      compared to revisional surgeries. There was one mortality post-primary surgery
      and no post-revisional surgical mortalities. CONCLUSIONS: Revisional bariatric
      surgery for complications related to the primary surgery is safe but had reduced
      excess weight loss compared to the initial surgery.

PMID- 26314352
TI  - The effect of drought on photosynthetic plasticity in Marrubium vulgare plants
      growing at low and high altitudes.
AB  - Photosynthesis is a biological process most affected by water deficit. Plants
      have various photosynthetic mechanisms that are matched to specific climatic
      zones. We studied the photosynthetic plasticity of C3 plants at water deficit
      using ecotypes of Marrubium vulgare L. from high (2,200 m) and low (1,100 m)
      elevation sites in the Mishou-Dagh Mountains of Iran. Under experimental drought,
      high-altitude plants showed more tolerance to water stress based on most of the
      parameters studied as compared to the low-altitude plants. Increased tolerance in
      high-altitude plants was achieved by lower levels of daytime stomatal conductance
      (g s) and reduced damaging effect on maximal quantum yield of photosystem II
      (PSII) (F v /F m ) coupled with higher levels of carotenoids and non
      photochemical quenching (NPQ). High-altitude plants exhibited higher water use
      efficiency (WUE) than that in low-altitude plants depending on the presence of
      thick leaves and the reduced daytime stomatal conductance. Additionally, we have
      studied the oscillation in H(+) content and diel gas exchange patterns to
      determine the occurrence of C3 or weak CAM (Crassulacean acid metabolism) in M.
      vulgare through 15 days drought stress. Under water-stressed conditions, low
      altitude plants exhibited stomatal conductance and acid fluctuations
      characteristic of C3 photosynthesis, though high-altitude plants exhibited more
      pronounced increases in nocturnal acidity and phosphoenolpyruvate carboxylase
      (PEPC) activity, suggesting photosynthetic flexibility. These results indicated
      that the regulation of carotenoids, NPQ, stomatal conductance and diel patterns
      of CO2 exchange presented the larger differences among studied plants at
      different altitudes and seem to be the protecting mechanisms controlling the
      photosynthetic performance of M. vulgare plants under drought conditions. 

PMID- 26314353
TI  - INTERGENERATIONAL EDUCATIONAL ATTAINMENT, FAMILY CHARACTERISTICS AND CHILD
      OBESITY.
AB  - This study used US National Longitudinal Study of Youth data to explore how
      exposure to different socioeconomic conditions (proxied by maternal education)
      before birth can shape child weight. Using endogenous selection regression
      models, the findings suggest that educational selectivity affects weight gain.
      Mothers whose mothers graduated from high school were more likely to complete
      high school, and mothers reared in an intact family had higher levels of
      education. However, mothers who had given birth as a teenager had the same
      educational outcomes as mothers who gave birth in their post-teenage years. Based
      on this intergenerational educational selectivity, caretaking (e.g. breast
      feeding) was found to be associated with a lower child body mass index (BMI),
      while negative maternal characteristics (e.g. mothers with high BMIs) were
      associated with higher child BMIs. Thus, educational selectivity influences child
      health through values passed on to the child and the lifestyle in which the child
      is reared. Maternal education may be tied to parenting, which relates to child
      obesity risk. 

PMID- 26314354
TI  - Ischemic preconditioning and thrombosis.

PMID- 26314355
TI  - Microcirculation: an early prognostic factor in the control of blood pressure.

PMID- 26314357
TI  - Restenosis after endovascular revascularization in peripheral artery disease.
AB  - Endovascular revascularization (EVR) plays a leading role in the therapy of
      peripheral artery disease. The acute success rates of EVR in all anatomic
      territories and of all TASC lesions are excellent (> 95%). However, the
      occurrence of restenoses after EVR such as percutaneous transluminal angioplasty
      and particularly after stenting, poses a substantial limitation to the success of
      the procedure. Influenced by patient's comorbidities, the severity of
      arteriosclerotic disease, lesion length and morphology as well as the techniques
      and devices used for EVR, the long-term outcome of EVR deteriorates markedly from
      the aortoiliac to the infrapopliteal segments of the lower limbs. The development
      of drug-coated balloons and drug-eluting stents reduced the occurrence of
      restenosis leading to considerably improved primary patency rates in the
      femoropopliteal segments. This review aims to provide an overview about the
      underlying mechanisms and current relevance of the various options in the field
      of EVR with regard to the rate of restenosis. 

PMID- 26314356
TI  - Markers of preclinical atherosclerosis and their clinical relevance.
AB  - The estimation of risk for atherosclerotic and cardiovascular events based only
      on the presence of classical risk factors is often insufficient. Therefore,
      efforts have been made to find markers that indicate the presence of preclinical
      disease in individual subjects: blood markers of atherosclerosis and preclinical
      deterioration of the arterial wall. Elevated levels of several inflammatory
      mediators have been found in subjects with atherosclerosis. Increased basal
      levels of cytokines, the cell adhesion molecules, selectins and acute-phase
      reactants such as high sensitive C-reactive protein (hsCRP), fibrinogen, and
      serum amyloid A are related to an increased risk of cardiovascular events. For
      clinical purposes, the most promising inflammatory biomarker appears to be hsCRP.
      In the last decade, markers of plaque stability and unstable coronary artery
      disease have been sought. Further, markers of endothelial dysfunction, like
      circulating molecules as well as indicators of functional deterioration of the
      arterial wall were identified. It was shown that endothelial dysfunction is
      closely related to different risk factors of atherosclerosis, and to their
      intensity and duration. Intima-media thickness measurement has emerged as one of
      the methods of choice for determining the anatomic extent of preclinical
      atherosclerosis and for assessing cardiovascular risk.Determination of markers of
      preclinical atherosclerosis improve individual risk determination and could
      influence the decision of a clinician to intervene with medication and to use
      more aggressive treatment of risk factors in high risk subjects and in patients
      with atherosclerotic disease. 

PMID- 26314358
TI  - Favorable effect of aerobic exercise on arterial pressure and aortic pulse wave
      velocity during stress testing.
AB  - BACKGROUND: Increased central pulse wave velocity is a major risk factor for
      cardiovascular disease. The favorable influence of exercise on arterial stiffness
      (AS) and blood pressure (BP) has been reported exclusively at rest. The present
      study investigated the influence of a single bout of acute cycling on AS and BP
      during recovery and, moreover, during cold pressor stress testing. PROBANDS AND
      METHODS: 32 healthy men (33.7 +/- 8 years, BMI 24 +/- 2.5 kg/m2) performed a 60
      minute endurance exercise on a bicycle ergometer (45 % VO2max). Before and after
      exercise aortic pulse wave velocity (aPWV) as well as central and peripheral BP
      were measured non-invasively at rest and at the end of a 2 minute cold pressor
      test (CPT). RESULTS: Even after 60 minutes of recovery aPWV (- 0.22 +/- 0.3 m /
      sec) was significantly reduced (p < 0.01). Exercise decreased peripheral (- 8 +/-
      7 mmHg) and central (- 7 +/- 8 mmHg) systolic BP as well as peripheral (- 3 +/- 5
      mmHg) and central (- 4 +/- 7 mmHg) diastolic BP (p < 0.01). In comparison to
      measurements during CPT pre-exercise, there was a significant reduction in aPWV (
      0.19 +/- 0.3 m / sec), peripheral (- 6 +/- 10 mmHg) and central (- 5 +/- 8 mmHg)
      systolic BP as well as peripheral (- 3 +/- 6 mmHg) and central (- 3 +/- 6 mmHg)
      diastolic BP during CPT after exercise (p < 0.01). CONCLUSIONS: The present study
      suggests that acute endurance exercise leads not only to decreased BP but even
      more reduces aPWV as a measure of AS even after 60 minutes of recovery. In
      particular, the investigation provides evidence that acute moderate-intensity
      exercise has a favorable effect on BP and aPWV during stress testing.

PMID- 26314359
TI  - Local endothelial dysfunction does not affect global endothelial function.
AB  - BACKGROUND: The purpose of this study was to evaluate two alternative non
      invasive techniques for assessment of endothelial function in adults with special
      focus on their ability to monitor acute changes. PATIENTS AND METHODS: Twenty
      five clinically healthy men (mean age 24 +/- 2 years) underwent endothelial
      function measurements twice in fasting state and twice after experimental
      induction of transient endothelial dysfunction by oral application of 0.1g/kg L
      methionine and by ingestion of 500 ml whipped cream (30 % fat), respectively.
      Microvascular vasodilator responses to flickering-light by retinal vessel
      analysis and vascular responses to inhaled salbutamol by pulse wave analysis were
      assessed at each occasion. Ultrasound based flow-mediated dilation (FMD) was used
      as reference method. RESULTS: Transient endothelial dysfunction in response to
      acute hyperlipidaemia and hyperhomocysteinaemia was verified by blunted brachial
      responses to hyperaemia. Retinal vessel analysis demonstrated significantly
      impaired flicker-responses of retinal vessels to both challenges depending on the
      vessel type. Pulse wave analysis did not show any significant changes in
      salbutamol responses. Reproducibility of retinal vessel analysis was comparable
      to FMD and slightly better than pulse wave analysis. CONCLUSIONS: Acute changes
      in endothelial function can be monitored by retinal vessel analysis with
      comparable reproducibility as FMD. Salbutamol based pulse wave analysis is
      currently unsuited to detect endothelial dysfunction in serial measurements.

PMID- 26314360
TI  - Localized lower extremity ischemic preconditioning prevents against local
      thrombus formation.
AB  - BACKGROUND: Ischemic preconditioning (IPC) has many beneficial effects on the
      cardiovascular system. However, whether localized lower extremity IPC could be
      protective against the thrombogenic activity generated by lower extremity
      ischemia is unclear. MATERIAL AND METHODS: 41 male Sprague-Dawley rats were
      randomly assigned to either a IPC group or a sham group. The lower extremity
      blood inflow was previously treated with 4 cycles of 5 min ischemia followed by 5
      min of reperfusion by clamping the abdominal aortic just before ligature of the
      left iliac vein(LIV) in the IPC group. Rats in the sham group had a 40-minute
      blank before left iliac vein ligation. The rats were euthanized at day 2 after
      ligation and the thrombosed LIV was carefully dissected out, while thrombi
      harvested from the LIV were measured with weight (g), length (mm) and
      weight/length (mg/mm). Influence of IPC on coagulation function was also tested.
      RESULTS: 21 and 20 rats were randomly assigned to einter the IPC group or the
      control group. Left iliac vein thrombosis was successfully generated in all 41
      rats. IPC significantly protects the rats from experimental lower extremity
      thrombosis. Compared to control group, generated thrombus in rats in the IPC
      group showed significantly lower weight (2.73 +/- 0.16 mg vs 1.82 +/- 0.13 mg, P
      < 0.001), length (2.99 +/- 0.17 mm vs 2.44 +/- 0.08 mm, P < 0.009) and density
      (0.95 +/- 0.05 mg/mm vs 0.75 +/- 0.05 mg/mm, P = 0.01). Influence on coagulation
      function by IPC itself was not significant (P > 0.05). CONCLUSIONS: Our study
      demonstrated that localized lower extremity IPC could reduce DVT formation in
      rats in an in vivo experimental thrombosis model.

PMID- 26314361
TI  - Gender-based 30-day and long-term outcomes after carotid endarterectomy.
AB  - BACKGROUND: We analyses the effect of gender on short and long-term morbidity and
      mortality in carotid endarterectomy (CEA) under loco-regional anesthesia.
      PATIENTS AND METHODS: Patients who were entered into a prospectively compiled
      computerized database of unilateral, consecutive CEAs performed at our hospital
      from January 2000 to December 2010 were analysed. Endpoints were perioperative
      stroke and death, and overall long-term survival rates. Statistical analysis was
      used to determine the relationships between gender and outcomes after CEA. A Cox
      proportional hazard model was applied to determine independent risk factors for
      long term survival. RESULTS: A total of 1880 CEA procedures were performed in the
      period between 2000 and 2010. Overall, there were 28 (1.48 %) neurological
      deficits according to the ipsilateral carotid supply territory, including minor
      and major strokes. 7 occurred in the female group (1.19 %), and 21 in the male
      group (1.62 %) with no significant difference between the genders (p = 0.60). No
      significant difference emerged between female and male patients when
      postoperative neurological events according to the ipsilateral carotid supply
      territory were stratified by linical presentation (asymptomatic ICA stenosis: p =
      0.75; symptomatic ICA stenosis: p = 0.66). The late overall mortality rate was
      4.1% (n = 78) and 26/78 of these late deaths occurred in the female group (33 %).
      Log rank analysis of Kaplan Meier curves showed no statistically significant
      difference in long-term survival between the groups (p = 0.74). The multivariate
      risk factor analysis with the Cox proportinal hazard model revealed age (p <
      0.00), and smoking (p = 0,02) as independent risk factors for decreased long term
      survival. CONCLUSIONS: When considering short and long-term outcomes in patients
      receiving carotid endarterectomy in local anaesthesia gender should not be
      regarded as a factor on decision-making for carotid interventions in both
      symptomatic and asymptomatic patients.

PMID- 26314362
TI  - Comparison of periprocedural and long term outcomes of proximal versus distal
      cerebral protection method during carotid artery stenting.
AB  - BACKGROUND: The aim of this study was to assess the periprocedural and one-year
      outcomes of two different cerebral protection systems used during carotid artery
      stenting (CAS). PATIENTS AND METHODS: We enrolled 90 consecutive patients with
      carotid artery stenosis who underwent CAS with a proximal flow blockage
      protection system (mean age 69.7 +/- 8) or distal protection with a filter (mean
      age 70.8 +/- 7). RESULTS: CAS was performed successively on 89 patients (99 %).
      Adverse events were defined as major stroke, minor stroke, transient ischemic
      attack (TIA), myocardial infarction, and death. Two strokes, one TIA, one death,
      and one myocardial infarction were observed in-hospital. There were no
      significant differences in safety or benefits between the proximal flow blockage
      embolic protection system (n = 45) and the distal filter protection system (n =
      45) in terms of clinically apparent cerebral embolism, TIA, death, or myocardial
      infarction during the periprocedural stage or during the one-year follow-up
      period. CONCLUSIONS: Although it has been shown that the proximal flow blockage
      cerebral protection system decreases the risk of silent cerebral embolism, it has
      no advantage over the distal filter protection system in terms of adverse
      cerebrovascular or cardiac events during the periprocedural stage or during the
      long-term follow-up period.

PMID- 26314363
TI  - Laparoscopic treatment of celiac artery compression syndrome in children and
      adolescents.
AB  - BACKGROUND: The celiac artery compression syndrome (CACS) is a rarely diagnosed
      disorder, which is characterized by chronic abdominal pain and vegetative
      symptoms. The role of surgical treatment in celiac artery decompression has been
      discussed controversially by numerous authors. After first casuistic descriptions
      of a laparoscopic treatment in adults we established this novel minimally
      invasive procedure for treatment in children and adolescents. PATIENTS AND
      METHODS: Between 2005 and 2014 we operated 58 patients (47 female, 11 male) from
      7 to 25 years who had been diagnosed with celiac artery compression. The patients
      presented with severe chronic abdominal pain, vegetative symptoms and a reduced
      quality of life. Doppler sonography showed an increased blood flow velocity of
      the celiac artery with maximum of 190 - 450 cm/s (mean 259 cm/s).MR angiography
      demonstrated a characteristic hook-shaped appearance of the celiac artery with
      severe localized compression. RESULTS: All patients underwent laparoscopic
      decompression of the celiac artery. We observed complications in 3 patients (5,2
      %). Postoperatively all patients (100 %) were immediately free of abdominal pain.
      Doppler sonography showed a marked reduction in celiac blood flow velocity to 70 
      190 cm/s postoperatively (mean 178 cm/s). A return of vessel diameters to normal
      dimensions was documented by postoperative MR angiography. During a median follow
      up of 62 months we observed a recurrence of the celiac artery compression in 4
      patients (6,9 %). CONCLUSIONS: Laparoscopic treatment of celiac artery
      compression syndrome offers a novel, safe, reliable and, compared to open
      surgery, less invasive approach. The surgical treatment is indicated in patients
      with characteristic symptoms and typical findings at Doppler sonography and MRA
      after exclusion of other abdominal pathologies. The work-up of chronic abdominal
      pain in children and adolescents should include a color Doppler sonography to
      look for celiac artery compression.

PMID- 26314364
TI  - Thrombophilia and risk of VTE recurrence according to the age at the time of
      first VTE manifestation.
AB  - BACKGROUND: Whether screening for thrombophilia is useful for patients after a
      first episode of venous thromboembolism (VTE) is a controversial issue. However,
      the impact of thrombophilia on the risk of recurrence may vary depending on the
      patient's age at the time of the first VTE. PATIENTS AND METHODS: Of 1221 VTE
      patients (42 % males) registered in the MAISTHRO (MAin-ISar-THROmbosis) registry,
      261 experienced VTE recurrence during a 5-year follow-up after the
      discontinuation of anticoagulant therapy. RESULTS: Thrombophilia was more common
      among patients with VTE recurrence than those without (58.6 % vs. 50.3 %; p =
      0.017). Stratifying patients by the age at the time of their initial VTE, Cox
      proportional hazards analyses adjusted for age, sex and the presence or absence
      of established risk factors revealed a heterozygous prothrombin (PT) G20210A
      mutation (hazard ratio (HR) 2.65; 95 %-confidence interval (CI) 1.71 - 4.12; p <
      0.001), homozygosity/double heterozygosity for the factor V Leiden and/or PT
      mutation (HR 2.35; 95 %-CI 1.09 - 5.07, p = 0.030), and an antithrombin
      deficiency (HR 2.12; 95 %-CI 1.12 - 4.10; p = 0.021) to predict recurrent VTE in
      patients aged 40 years or older, whereas lupus anticoagulants (HR 3.05; 95%-CI
      1.40 - 6.66; p = 0.005) increased the risk of recurrence in younger patients.
      Subgroup analyses revealed an increased risk of recurrence for a heterozygous
      factor V Leiden mutation only in young females without hormonal treatment whereas
      the predictive value of a heterozygous PT mutation was restricted to males over
      the age of 40 years. CONCLUSIONS: Our data do not support a preference of younger
      patients for thrombophilia testing after a first venous thromboembolic event.

PMID- 26314365
TI  - High amputation rates and mortality - is critical limb ischemia still a losing
      game?

PMID- 26314366
TI  - [Prof. Dr. med. Alfred Bollinger (1932-2015)].

PMID- 26314367
TI  - Fluorescence recovery after photobleaching in material and life sciences: putting
      theory into practice.
AB  - Fluorescence recovery after photobleaching (FRAP) is a versatile tool for
      determining diffusion and interaction/binding properties in biological and
      material sciences. An understanding of the mechanisms controlling the diffusion
      requires a deep understanding of structure-interaction-diffusion relationships.
      In cell biology, for instance, this applies to the movement of proteins and
      lipids in the plasma membrane, cytoplasm and nucleus. In industrial applications
      related to pharmaceutics, foods, textiles, hygiene products and cosmetics, the
      diffusion of solutes and solvent molecules contributes strongly to the properties
      and functionality of the final product. All these systems are heterogeneous, and
      accurate quantification of the mass transport processes at the local level is
      therefore essential to the understanding of the properties of soft
      (bio)materials. FRAP is a commonly used fluorescence microscopy-based technique
      to determine local molecular transport at the micrometer scale. A brief high
      intensity laser pulse is locally applied to the sample, causing substantial
      photobleaching of the fluorescent molecules within the illuminated area. This
      causes a local concentration gradient of fluorescent molecules, leading to
      diffusional influx of intact fluorophores from the local surroundings into the
      bleached area. Quantitative information on the molecular transport can be
      extracted from the time evolution of the fluorescence recovery in the bleached
      area using a suitable model. A multitude of FRAP models has been developed over
      the years, each based on specific assumptions. This makes it challenging for the
      non-specialist to decide which model is best suited for a particular application.
      Furthermore, there are many subtleties in performing accurate FRAP experiments.
      For these reasons, this review aims to provide an extensive tutorial covering the
      essential theoretical and practical aspects so as to enable accurate quantitative
      FRAP experiments for molecular transport measurements in soft (bio)materials. 

PMID- 26314368
TI  - Treatment persistence among patients with rheumatoid disease (RA, AS, PsA)
      treated with subcutaneous biologics in Germany.
AB  - Patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and
      psoriatic arthritis (PsA) are frequently treated with subcutaneous biologic
      therapies when disease progresses or when response to synthetic disease-modifying
      antirheumatic drugs (DMARDs) is inadequate. This study analyzed treatment
      persistence and treatment patterns for RA, AS, and PsA patients in Germany
      initiating subcutaneous biologic therapies with and without prior DMARDs use. A
      retrospective cohort study was conducted using the Electronic Medical Record
      database of IMS Disease Analyzer, Germany. Patients who were >=18 years old; had
      at least one ICD-10 diagnosis code of RA, AS, or PsA during the study period; and
      had exposure to a subcutaneous biologic agent between January 1, 2009 and June
      30, 2012 were selected. Patients were required to have continuous observation
      >=12 months prior to and after index medication date. Persistence was defined as
      consecutive days from treatment initiation until treatment discontinuation (>=60
      day lapse in medication coverage). Patients were stratified by pre-index use of
      DMARDs. Kaplan-Meier analysis was conducted to assess time to discontinuation,
      and logistic regression was conducted to identify characteristics associated with
      persistence. A total of 576 RA, 108 AS, and 197 PsA patients without biologic
      experience during the pre-index period were selected. The percentages of RA, AS,
      and PsA patients persistent >=12 months were 51.9, 48.1, and 57.9 %,
      respectively. Median persistent time over 12 months was 365.0 days for RA (mean
      245.9 days), 281.0 for AS (mean 228.5), and 365.0 for PsA (mean 264.1). In the RA
      cohort, a significantly higher proportion of those with pre-index DMARD use were
      persistent compared to those without pre-index DMARD (56.1 vs. 33.3 %, p =
      0.0001). No significant differences were observed for the AS and PsA cohorts.
      Multivariate analyses confirmed that DMARD-experienced patients were 2.45 times
      more likely to be persistent with subcutaneous biologic therapy in the RA cohort.
      Switching between subcutaneous biologics occurred in <10 % of patients in all
      three cohorts. In the subpopulations with at least two prescriptions for the
      index subcutaneous biologic and who remained persistent on the index subcutaneous
      biologic, dose escalation of >=50 % occurred in 50, 60, and 49 % in the RA, AS,
      and PsA cohorts, respectively. Among RA, AS, and PsA patients newly initiating
      subcutaneous biologic agents in Germany, persistence at 12 months is relatively
      low (48-58 %). For the RA cohort, patients with pre-index DMARD use are more
      persistent than patients without. The majority of patients do not switch between
      subcutaneous biologics. A notable proportion of patients who remained persistent
      on their index subcutaneous biologic had a dose escalation. There are
      opportunities to improve outcomes of patient with rheumatoid disease through
      improved medication persistence.

PMID- 26314370
TI  - Freeze-drying for sustainable synthesis of nitrogen doped porous carbon cryogel
      with enhanced supercapacitor and lithium ion storage performance.
AB  - A chitosan (CS) based nitrogen doped carbon cryogel with a high specific surface
      area (SSA) has been directly synthesized via a combined process of freeze-drying
      and high-temperature carbonization without adding any activation agents. The as
      made carbon cryogel demonstrates an SSA up to 1025 m(2) g(-1) and a high nitrogen
      content of 5.98 wt%, while its counterpart derived from CS powder only shows an
      SSA of 26 m(2) g(-1). Freeze-drying is a determining factor for the formation of
      carbon cryogel with a high SSA, where the CS powder with a size of ca. 200 MUm is
      transformed into the sheet-shaped cryogel with a thickness of 5-8 MUm. The as
      made carbon cryogel keeps the sheet-shaped structure and the abundant pores are
      formed in situ and decorated inside the sheets during carbonization. The carbon
      cryogel shows significantly enhanced performance as supercapacitor and lithium
      ion battery electrodes in terms of capacity and rate capability due to its quasi
      two-dimensional (2D) structure with reduced thickness. The proposed method may
      provide a simple approach to configure 2D biomass-derived advanced carbon
      materials for energy storage devices. 

PMID- 26314369
TI  - Zn(II)-curc targets p53 in thyroid cancer cells.
AB  - TP53 mutation is a common event in many cancers, including thyroid carcinoma.
      Defective p53 activity promotes cancer resistance to therapies and a more
      malignant phenotype, acquiring oncogenic functions. Rescuing the function of
      mutant p53 (mutp53) protein is an attractive anticancer therapeutic strategy.
      Zn(II)-curc is a novel small molecule that has been shown to target mutp53
      protein in several cancer cells, but its effect in thyroid cancer cells remains
      unclear. Here, we investigated whether Zn(II)-curc could affect p53 in thyroid
      cancer cells with both p53 mutation (R273H) and wild-type p53. Zn(II)-curc
      induced mutp53H273 downregulation and reactivation of wild-type functions, such
      as binding to canonical target promoters and target gene transactivation. This
      latter effect was similar to that induced by PRIMA-1. In addition, Zn(II)-curc
      triggered p53 target gene expression in wild-type p53-carrying cells. In
      combination treatments, Zn(II)-curc enhanced the antitumor activity of
      chemotherapeutic drugs, in both mutant and wild-type-carrying cancer cells. Taken
      together, our data indicate that Zn(II)-curc promotes the reactivation of p53 in
      thyroid cancer cells, providing in vitro evidence for a potential therapeutic
      approach in thyroid cancers.

PMID- 26314371
TI  - Doping of TiO2 for sensitized solar cells.
AB  - This review gives a detailed summary and evaluation of the use of TiO2 doping to
      improve the performance of dye sensitized solar cells. Doping has a major effect
      on the band structure and trap states of TiO2, which in turn affect important
      properties such as the conduction band energy, charge transport, recombination
      and collection. The defect states of TiO2 are highly dependent on the synthesis
      method and thus the effect of doping may vary for different synthesis techniques,
      making it difficult to compare the suitability of different dopants. High
      throughput methods may be employed to achieve a rough prediction on the
      suitability of dopants for a specific synthesis method. It was however found that
      nearly every employed dopant can be used to increase device performance,
      indicating that the improvement is not so much caused by the dopant itself, as by
      the defects it eliminates from TiO2. Furthermore, with the field shifting from
      dye sensitized solar cells to perovskite solar cells, the role doping can play to
      further advance this emerging field is also discussed. 

PMID- 26314372
TI  - Experimental observation of the elusive double-peak structure in R-dependent
      strong-field ionization rate of H2(+).
AB  - When a diatomic molecule is ionized by an intense laser field, the ionization
      rate depends very strongly on the inter-nuclear separation. That dependence
      exhibits a pronounced maximum at the inter-nuclear separation known as the
      "critical distance". This phenomenon was first demonstrated theoretically in
      H2(+) and became known as "charge-resonance enhanced ionization" (CREI, in
      reference to a proposed physical mechanism) or simply "enhanced ionization"(EI).
      All theoretical models of this phenomenon predict a double-peak structure in the
      R-dependent ionization rate of H2(+). However, such double-peak structure has
      never been observed experimentally. It was even suggested that it is impossible
      to observe due to fast motion of the nuclear wavepackets. Here we report a few
      cycle pump-probe experiment which clearly resolves that elusive double-peak
      structure. In the experiment, an expanding H2(+) ion produced by an intense pump
      pulse is probed by a much weaker probe pulse. The predicted double-peak structure
      is clearly seen in delay-dependent kinetic energy spectra of protons when pump
      and probe pulses are polarized parallel to each other. No structure is seen when
      the probe is polarized perpendicular to the pump. 

PMID- 26314373
TI  - Measurement of the cleavage energy of graphite.
AB  - The basal plane cleavage energy (CE) of graphite is a key material parameter for
      understanding many of the unusual properties of graphite, graphene and carbon
      nanotubes. Nonetheless, a wide range of values for the CE has been reported and
      no consensus has yet emerged. Here we report the first direct, accurate
      experimental measurement of the CE of graphite using a novel method based on the
      self-retraction phenomenon in graphite. The measured value, 0.37+/-0.01 J m(-2)
      for the incommensurate state of bicrystal graphite, is nearly invariant with
      respect to temperature (22  degrees C<=T<=198  degrees C) and bicrystal twist
      angle, and insensitive to impurities from the atmosphere. The CE for the ideal
      ABAB graphite stacking, 0.39+/-0.02 J m(-2), is calculated based on a combination
      of the measured CE and a theoretical calculation. These experimental measurements
      are also ideal for use in evaluating the efficacy of competing theoretical
      approaches.

PMID- 26314375
TI  - Brief Report: Interleukin-38 Exerts Antiinflammatory Functions and Is Associated
      With Disease Activity in Systemic Lupus Erythematosus.
AB  - OBJECTIVE: Knowledge of interleukin-38 (IL-38), formerly IL-1 family member 10,
      is sparse, but Il1f10 polymorphisms are associated with inflammatory diseases,
      and recombinant IL-38 inhibits inflammatory responses similar to those reported
      in the context of systemic lupus erythematosus (SLE). We undertook this study to
      explore the function of endogenous IL-38 in human peripheral blood mononuclear
      cells (PBMCs) as well as its abundance in serum in a well-characterized cohort of
      SLE patients. METHODS: Serum IL-38 and IL-10 levels were quantified by enzyme
      linked immunosorbent assay in 142 SLE patients at <=3 consecutive visits and in
      28 healthy volunteers. To assess IL-38 function, we silenced IL-38 in PBMCs from
      healthy donors using IL-38 small interfering RNA (siRNA). RESULTS: IL-38 (63
      5,928 pg/ml) was detectable in 16% of 372 serum samples. IL-38 abundance was
      significantly higher in samples from SLE patients than in samples from healthy
      controls (P = 0.004) and 11-fold higher in patients with active disease (SLE
      Disease Activity Index 2000 [SLEDAI-2K] score of >=4) than in those with inactive
      disease (SLEDAI-2K score of <4) (P = 0.044). Importantly, IL-38 detection was
      associated with increased risk of renal lupus (relative risk [RR] 1.6, P = 0.027)
      and central nervous system lupus (RR 2.3, P = 0.034), and detectable baseline IL
      38 entailed a 1.6-fold increased risk of subsequently meeting criteria for
      persistently active disease (P = 0.0097). Longitudinal time-adjusted mean IL-38
      concentration was also 6-fold higher in patients with persistently active disease
      than in those without (P = 0.023). Remarkably, PBMCs treated with IL-38 siRNA
      produced up to 28-fold more of the proinflammatory mediators IL-6, CCL2, and
      APRIL than did control siRNA-transfected cells upon stimulation with Toll-like
      receptor agonists. Similarly, in SLE patients, the antiinflammatory cytokine IL
      10 was 5-fold more abundant when IL-38 was detectable. CONCLUSION: This is the
      first study of the function of endogenous IL-38, and the data suggest that IL-38
      may be protective in SLE. A strong association between IL-38 and SLE severity
      suggests that IL-38 expression is driven by processes linked to SLE pathogenesis.
      Exploitation of the regulatory effects of IL-38 may represent a promising
      therapeutic strategy in SLE.

PMID- 26314376
TI  - Coordination-directed self-assembly of a simple benzothiadiazole-fused
      tetrathiafulvalene to low-bandgap metallogels.
AB  - Coordination-driven gelation of a benzothiadiazole-fused tetrathiafulvalene (TTF)
      is demonstrated. This is the first work reporting highly stable metallogels based
      on a donor-acceptor conjugate with such a simple structure for the construction
      of new low-bandgap materials with various functional properties and novel
      nanostructures. 

PMID- 26314374
TI  - Confirmation of CCR6 as a risk factor for anti-topoisomerase I antibodies in
      systemic sclerosis.
AB  - OBJECTIVES: The current knowledge of the influence of systemic sclerosis (SSc)
      risk loci in the clinical sub-phenotypes is still limited. The main limitation
      lies in the low frequency of some sub-phenotypes which could be solved by
      replication studies in independent cohorts and meta-analysis between studies. In
      this regard, CCR6 gene variants have been recently associated with anti
      topoisomerase I positive (ATA+) production in SSc patients in a candidate gene
      study. This gene has been proposed to have a critical role in IL-17-driven
      autoimmunity in human diseases. METHODS: In order to confirm the association
      between CCR6 and ATA+ SSc patients, we performed an independent replication study
      in populations of European ancestry. We studied two CCR6 genetic variants
      (rs968334 and rs3093024) in a total of 901 ATA+ SSc cases, 3,258 ATA- SSc cases
      and 7,865 healthy controls and compared allelic frequencies for those SNPs in
      ATA+ SSc with healthy controls and also with ATA- SSc patients. RESULTS: The
      comparison performed between ATA+ SSc patients and healthy controls showed
      significant association with SNP rs968334 (p=4.88x10(-2), OR=1.11). When we
      compared ATA+ SSc cases with ATA- SSc, both SNPs, rs3093024 and rs968334, showed
      significant associations (p=2.89x10(-2), OR=1.13; p=1.69x10(-2), OR=1.15).
      Finally, in order to increase even more sample size and statistical power, we
      meta-analysed our study with the previous reported and found a significant
      association between SNP rs3093024 and ATA+ SSc patients (p=1.00x10(-4), OR=1.16)
      comparing with healthy controls. CONCLUSIONS: Our work confirms the association
      of CCR6 gene and ATA+ SSc patients.

PMID- 26314377
TI  - Two-photon uncageable enzyme inhibitors bearing targeting vectors.
AB  - The activity of two cyclooxygenase-2 enzyme inhibitors, Celecoxib and
      Lumiracoxib, could be suppressed by coupling to photo-labile protecting groups,
      so-called photocages. These groups could be further functionalized with a peptide
      targeting vector for specific cellular delivery. The enzyme inhibition potential
      of the cyclooxygenase-2 inhibitors could be regained upon two-photon excitation
      with tissue-transparent near-IR light at 800 nm. 

PMID- 26314378
TI  - A nitrogen and sulfur dual-doped carbon derived from polyrhodanine@cellulose for
      advanced lithium-sulfur batteries.
AB  - A sulfur electrode exhibiting strong polysulfide chemisorption using a porous N,
      S dual-doped carbon is reported. The synergistic functionalization from the N and
      S heteroatoms dramatically modifies the electron density distribution and leads
      to much stronger polysulfide binding. X-ray photoelectron spectroscopy studies
      combined with ab initio calculations reveal strong Li(+) -N and Sn (2-) -S
      interactions. The sulfur electrodes exhibit an ultralow capacity fading of 0.052%
      per cycle over 1100 cycles. 

PMID- 26314379
TI  - Spatial differentiation of gene expression in Aspergillus niger colony grown for
      sugar beet pulp utilization.
AB  - Degradation of plant biomass to fermentable sugars is of critical importance for
      the use of plant materials for biofuels. Filamentous fungi are ubiquitous
      organisms and major plant biomass degraders. Single colonies of some fungal
      species can colonize massive areas as large as five soccer stadia. During growth,
      the mycelium encounters heterogeneous carbon sources. Here we assessed whether
      substrate heterogeneity is a major determinant of spatial gene expression in
      colonies of Aspergillus niger. We analyzed whole-genome gene expression in five
      concentric zones of 5-day-old colonies utilizing sugar beet pulp as a complex
      carbon source. Growth, protein production and secretion occurred throughout the
      colony. Genes involved in carbon catabolism were expressed uniformly from the
      centre to the periphery whereas genes encoding plant biomass degrading enzymes
      and nitrate utilization were expressed differentially across the colony. A
      combined adaptive response of carbon-catabolism and enzyme production to locally
      available monosaccharides was observed. Finally, our results demonstrate that A.
      niger employs different enzymatic tools to adapt its metabolism as it colonizes
      complex environments. 

PMID- 26314381
TI  - Protein 2DE reference map of the anterior midgut of the blood-sucking bug
      Rhodnius prolixus.
AB  - Rhodnius prolixus is an important vector of Trypanosoma cruzi, the causative
      agent of Chagas' disease, an illness that affects 20% of Latin America
      population. The obligatory course of the parasite in the vector digestive tract
      has made it an important target for investigation in order to control the
      parasite transmission and thus interrupt its biological cycle in the insect
      vector. Therefore, an insight into the vector midgut physiology is valuable for
      insect control as well as to provide potential novel targets for drugs and
      vaccines development and thus disease treatment. In this study, the first 2DE map
      of R. prolixus anterior midgut is described. Proteins were separated by 2DE and
      analyzed by nano-LC MS/MS. The results yielded 489 proteins from 475 spots. These
      proteins were classified into 28 functional groups and their physiological roles
      in the insect midgut are discussed. All MS data have been deposited in the
      ProteomeXchange with identifiers PXD001488 and PXD001489
      (http://proteomecentral.proteomexchange.org/dataset/PXD001488,
      http://proteomecentral.proteomexchange.org/dataset/PXD001489). 

PMID- 26314380
TI  - Reproducibility and effect of tissue composition on cerebellar gamma-aminobutyric
      acid (GABA) MRS in an elderly population.
AB  - MRS provides a valuable tool for the non-invasive detection of brain gamma
      aminobutyric acid (GABA) in vivo. GABAergic dysfunction has been observed in the
      aging cerebellum. The study of cerebellar GABA changes is of considerable
      interest in understanding certain age-related motor disorders. However, little is
      known about the reproducibility of GABA MRS in an aged population. Therefore,
      this study aimed to explore the feasibility and reproducibility of GABA MRS in
      the aged cerebellum at 3.0 T and to examine the effect of differing tissue
      composition on GABA measurements. MRI and (1)H MRS examinations were performed on
      10 healthy elderly volunteers (mean age, 75.2 +/- 6.5 years) using a 3.0-T
      Siemens Tim Trio scanner. Among them, five subjects were scanned twice to assess
      the short-term reproducibility. The MEGA-PRESS (Mescher-Garwood point-resolved
      spectroscopy) J-editing sequence was used for GABA detection in two volumes of
      interest (VOIs) in the left and right cerebellar dentate. MRS data processing and
      quantification were performed with LCModel 6.3-0L using two separate basis sets,
      generated from density matrix simulations using published values for chemical
      shifts and J couplings. Raw metabolite levels from LCModel outputs were corrected
      for cerebrospinal fluid contamination and relaxation. GABA-edited spectra yielded
      robust and stable GABA measurements with averaged intra-individual coefficients
      of variation for corrected GABA+ between 4.0 +/- 2.8% and 13.4 +/- 6.3%, and
      inter-individual coefficients of variation between 12.6% and 24.2%. In addition,
      there was a significant correlation between GABA+ obtained with the two LCModel
      basis sets. Overall, our results demonstrated the feasibility and reproducibility
      of cerebellar GABA-edited MRS at 3.0 T in an elderly population. This information
      might be helpful for studies using this technique to study GABA changes in normal
      or diseased aging brain, e.g. for power calculations and the interpretation of
      longitudinal observations.

PMID- 26314382
TI  - Morphological defects in native Japanese fir trees around the Fukushima Daiichi
      Nuclear Power Plant.
AB  - After the accident at the Fukushima Daiichi Nuclear Power Plant (F1NPP) in March
      2011, much attention has been paid to the biological consequences of the released
      radionuclides into the surrounding area. We investigated the morphological
      changes in Japanese fir, a Japanese endemic native conifer, at locations near the
      F1NPP. Japanese fir populations near the F1NPP showed a significantly increased
      number of morphological defects, involving deletions of leader shoots of the main
      axis, compared to a control population far from the F1NPP. The frequency of the
      defects corresponded to the radioactive contamination levels of the observation
      sites. A significant increase in deletions of the leader shoots became apparent
      in those that elongated after the spring of 2012, a year after the accident.
      These results suggest possibility that the contamination by radionuclides
      contributed to the morphological defects in Japanese fir trees in the area near
      the F1NPP. 

PMID- 26314383
TI  - Dyes and Redox Couples with Matched Energy Levels: Elimination of the Dye
      Regeneration Energy Loss in Dye-Sensitized Solar Cells.
AB  - In dye-sensitized solar cells (DSSCs), a significant dye-regeneration force
      (DeltaG(reg)(0)>=0.5 eV) is usually required for effective dye regeneration,
      which results in a major energy loss and limits the energy-conversion efficiency
      of state-of-art DSSCs. We demonstrate that when dye molecules and redox couples
      that possess similar conjugated ligands are used, efficient dye regeneration
      occurs with zero or close-to-zero driving force. By using Ru(dcbpy)(bpy)2(2+) as
      the dye and Ru(bpy)2(MeIm)2(3+//2+) as the redox couple, a short-circuit current
      (J(sc)) of 4 mA cm(-2) and an open-circuit voltage (V(oc)) of 0.9 V were obtained
      with a DeltaG(reg)(0) of 0.07 eV. The same was observed for the N3 dye and
      Ru(bpy)2(SCN)2(1+/0) (DeltaG(reg)(0)=0.0 eV), which produced an J(sc) of 2.5 mA
      cm(-2) and V(oc) of 0.6 V. Charge recombination occurs at pinholes, limiting the
      performance of the cells. This proof-of-concept study demonstrates that high
      V(oc) values can be attained by significantly curtailing the dye-regeneration
      force.

PMID- 26314384
TI  - Are different measures of depressive symptoms in old age comparable? An analysis
      of the CES-D and Euro-D scales in 13 countries.
AB  - The Centre for Epidemiologic Studies of Depression (CES-D) and the Euro-D are
      commonly used depressive symptom scales but their comparability has not been
      assessed to date. This article aims to contribute to the literature comparing the
      drivers of depression in old age across countries by examining whether CES-D (in
      its eight-item short version) and Euro-D are comparable. Data from the Survey of
      Health, Ageing and Retirement in Europe (SHARE, N = 15,487) covering 13 countries
      was used to examine the scales' distributional properties, systematic differences
      between population subgroups, sensitivity and specificity, and associations with
      established risk factors for depression in old age. CES-D and Euro-D were
      strongly correlated (r = 0.6819, p < 0.000). However, agreement between the two
      scales was moderate. There were systematic discrepancies in scores by demographic
      characteristics. CES-D captures a more extreme pool of depressed individuals than
      Euro-D. Although associations with risk factors are always in the same direction,
      they are often stronger for CES-D than Euro-D. Findings highlight the need to be
      cautious when comparing depression levels and associations with risk factors
      between surveys using different measures of depressive symptoms. Copyright (c)
      2015 John Wiley & Sons, Ltd. 

PMID- 26314385
TI  - Validation of the standardised assessment of personality--abbreviated scale in a
      general population sample.
AB  - BACKGROUND: Personality disorder (PD) is associated with important health
      outcomes in the general population. However, the length of diagnostic interviews
      poses a significant barrier to obtaining large scale, population-based data on
      PD. A brief screen for the identification of people at high risk of PD in the
      general population could be extremely valuable for both clinicians and
      researchers. AIM: We set out to validate the Standardised Assessment of
      Personality - Abbreviated Scale (SAPAS), in a general population sample, using
      the Structured Clinical Interviews for DSM-IV Personality Disorders (SCID-II) as
      a gold standard. METHOD: One hundred and ten randomly selected, community
      dwelling adults were administered the SAPAS screening interview. The SCID-II was
      subsequently administered by a clinical interviewer blind to the initial SAPAS
      score. Receiver operating characteristic analysis was used to assess the
      discriminatory performance of the SAPAS, relative to the SCID-II. RESULTS: Area
      under the curve for the SAPAS was 0.70 (95% CI = 0.60 to 0.80; p < 0.001),
      indicating moderate overall discriminatory accuracy. A cut point score of 4 on
      the SAPAS correctly classified 58% of participants. At this cut point, the
      sensitivity and specificity were 0.69 and 0.53 respectively. CONCLUSION: The
      SAPAS operates less efficiently as a screen in general population samples and is
      probably most usefully applied in clinical populations.

PMID- 26314386
TI  - Detection of selective sweeps in structured populations: a comparison of recent
      methods.
AB  - Identifying genomic regions targeted by positive selection has been a long
      standing interest of evolutionary biologists. This objective was difficult to
      achieve until the recent emergence of next-generation sequencing, which is
      fostering the development of large-scale catalogues of genetic variation for
      increasing number of species. Several statistical methods have been recently
      developed to analyse these rich data sets, but there is still a poor
      understanding of the conditions under which these methods produce reliable
      results. This study aims at filling this gap by assessing the performance of
      genome-scan methods that consider explicitly the physical linkage among SNPs
      surrounding a selected variant. Our study compares the performance of seven
      recent methods for the detection of selective sweeps (iHS, nSL, EHHST, xp-EHH, XP
      EHHST, XPCLR and hapFLK). We use an individual-based simulation approach to
      investigate the power and accuracy of these methods under a wide range of
      population models under both hard and soft sweeps. Our results indicate that
      XPCLR and hapFLK perform best and can detect soft sweeps under simple population
      structure scenarios if migration rate is low. All methods perform poorly with
      moderate-to-high migration rates, or with weak selection and very poorly under a
      hierarchical population structure. Finally, no single method is able to detect
      both starting and nearly completed selective sweeps. However, combining several
      methods (XPCLR or hapFLK with iHS or nSL) can greatly increase the power to
      pinpoint the selected region.

PMID- 26314387
TI  - Fluorescence in situ hybridization (FISH) results in HER2 score 1+ and 2+ breast
      cancers.

PMID- 26314388
TI  - Physiological characteristics of elite high-altitude climbers.
AB  - Factors underlying the amplitude of exercise performance reduction at altitude
      and the development of high-altitude illnesses are not completely understood. To
      better describe these mechanisms, we assessed cardiorespiratory and tissue
      oxygenation responses to hypoxia in elite high-altitude climbers. Eleven high
      altitude climbers were matched with 11 non-climber trained controls according to
      gender, age, and fitness level (maximal oxygen consumption, VO2 max ). Subjects
      performed two maximal incremental cycling tests, in normoxia and in hypoxia
      (inspiratory oxygen fraction: 0.12). Cardiorespiratory measurements and tissue
      (cerebral and muscle) oxygenation were assessed continuously. Hypoxic ventilatory
      and cardiac responses were determined at rest and during exercise; hypercapnic
      ventilatory response was determined at rest. In hypoxia, climbers exhibited
      similar reductions to controls in VO2 max (climbers -39 +/- 7% vs controls -39 +/
      9%), maximal power output (-27 +/- 5% vs -26 +/- 4%), and arterial oxygen
      saturation (SpO2 ). However, climbers had lower hypoxic ventilatory response
      during exercise (1.7 +/- 0.5 vs 2.6 +/- 0.7 L/min/%; P < 0.05) and lower
      hypercapnic ventilatory response (1.8 +/- 1.4 vs 3.8 +/- 2.5 mL/min/mmHg; P <
      0.05). Finally, climbers exhibited slower breathing frequency, larger tidal
      volume and larger muscle oxygenation index. These results suggest that elite
      climbers show some specific ventilatory and muscular responses to hypoxia
      possibly because of genetic factors or adaptation to frequent high-altitude
      climbing. 

PMID- 26314389
TI  - Peripheral blood eosinophils and other non-invasive biomarkers can monitor
      treatment response in eosinophilic oesophagitis.
AB  - BACKGROUND: Monitoring of the treatment response in eosinophilic oesophagitis
      (EoE) requires structured endoscopical and histological examination of the
      oesophagus. Less invasive methods would be highly desirable. AIM: To evaluate the
      utility of several EoE-associated blood and serum markers in order to non
      invasively monitor the response to treatment with swallowed topical
      corticosteroids in adult EoE patients. METHODS: In a randomised, controlled
      double-blind trial blood samples of EoE patients (n = 69) were collected at
      baseline and after 14 days of treatment with budesonide (n = 51) or placebo (n =
      18) respectively. Absolute blood eosinophil count (AEC) as well as serum levels
      of CCL-17, CCL-18, CCL-26, eosinophil-cationic-protein (ECP) and mast cell
      tryptase (MCT) were determined and correlated with oesophageal eosinophil density
      and with symptom and endoscopy scores. RESULTS: Histological remission, defined
      as mean number of <16 eos/mm(2) hpf at end-of-treatment, was achieved in 98% of
      the budesonide and 0% of the placebo recipients. AEC [380.2 vs. 214.7/mm(3) (P =
      0.0001)], serum-CCL-17 [294.3 vs. 257.9 pg/mL (P = 0.0019)], -CCL-26 [26.7 vs.
      16.2 pg/mL (P = 0.0058)], -ECP [45.5 +/- 44.7 vs. 27.5 +/- 25.0 MUg/L (P =
      0.0016)] and -MCT [5.3 +/- 2.9 vs. 4.5 +/- 2.6 MUg/L (P = 0.0019)] significantly
      decreased under budesonide but not under placebo. AEC significantly correlated
      with oesophageal eosinophil density before (r = 0.28, P = 0.0236) and after (r =
      0.42, P = 0.0004) budesonide treatment. In ROC-AUC analyses post-treatment values
      of AEC were significantly associated with histological remission (ROC-AUC 0.754;
      95% CI: 0.617-0.891; P = 0.0003). CONCLUSIONS: The budesonide-induced treatment
      response in EoE is mirrored by several blood and serum markers, and the absolute
      blood eosinophil count is the most valuable as it shows correlation with the
      oesophageal eosinophil density.

PMID- 26314390
TI  - Prevalence of Severe Fatigue Among Adolescents With Pediatric Rheumatic Diseases.
AB  - OBJECTIVE: To determine the prevalence of severe fatigue and fatigue-related
      limitations among adolescents with juvenile idiopathic arthritis (JIA) and other
      pediatric rheumatic diseases (PRDs). In addition, we assessed the effect of
      disease activity and pain on the severity of fatigue. METHODS: This cross
      sectional study included 175 patients (ages 10-18 years) who visited the
      pediatric rheumatology and immunology outpatient clinic at Wilhelmina Children's
      Hospital from April through July 2013. Patients completed validated
      questionnaires regarding fatigue, physical functioning, and school attendance.
      Disease activity in JIA patients was measured using the Juvenile Arthritis
      Disease Activity Score including 27 joints. The results were compared against a
      healthy control group. RESULTS: The prevalence of severe fatigue among patients
      with PRDs was 25.1%, which was significantly higher than among the healthy
      control group (P < 0.001). Fatigued patients had significantly lower levels of
      physical functioning compared to nonfatigued patients (62.1% versus 89.0%,
      respectively; P < 0.001) and a significantly higher percentage of school absences
      (21.2% versus 11.6%, respectively; P = 0.005). Among JIA patients, the level of
      pain was significantly correlated with fatigue. Finally, disease activity was not
      a predictor for fatigue. CONCLUSION: Fatigue is a common problem among teenagers
      with PRDs, with a higher prevalence among these patients than in the general
      population. Severe fatigue leads to significant impairments, including increased
      school absences and decreased physical functioning. Interestingly, fatigue was
      associated with pain, but not with the disease activity. Therefore, in this
      patient population, fatigue may be a promising therapeutic target for improving
      functioning, school attendance, and possibly pain as well.

PMID- 26314392
TI  - Perspectives on clinical possibility: elements of analysis.
AB  - Possibility is one of the most common modalities in reasoning and argumentation.
      Various kinds of modal concepts have been identified in philosophical and logical
      discussion of the metaphysics of modality. We focus here on the concept of
      clinical possibility. A critical analysis of what is intended as clinical
      possibility has not yet received sufficient examination, although the concept is
      extensively used in clinical reasoning. We present arguments to emphasize some
      desirable features associated with the concept of clinical possibility. We argue
      that almost all clinical possibilities are potentialities, that is, possibilities
      that may be actualized by effective, appropriate and feasible interventions.
      However, in some limited cases, even mere possibilities - which may or may not be
      actualized, since we do not have the required knowledge - may be involved in
      clinical reasoning, and we present some examples in this paper. We then introduce
      some basic views on the nature of possibility showing their validity and
      limitations when applied to the concept of clinical possibility. Lastly, we
      conjecture that clinical possibility is a normative modality that can be
      formalized in a multimodal system with epistemic and deontic logical operators. 

PMID- 26314393
TI  - Posteromedial thigh (PMT) propeller flap for perineoscrotal reconstruction: A
      case report.
AB  - Fournier's gangrene can lead to extensive defects of the perineoscrotal area with
      exposure of the testes. Such defect poses challenging tasks for both functional
      and cosmetic reconstruction. Due to its proximity, medial thigh skin appeared to
      be the most versatile donor site for perineoscrotal reconstruction. In this
      report, we present a case of reconstruction of a large perineoscrotal defect
      because of Fournier's gangrene using a posteromedial thigh (PMT) perforator
      propeller flap. A 58 year-old male who suffered from Fournier's gangrene resulted
      in a scrotal defect of 10 * 12 cm(2) with a large dead space. A pedicled PMT
      propeller flap measuring 9 * 23 cm(2) with two perforators that originated from
      the profunda femoris artery (PFA) was harvested for scrotal defect reconstruction
      and dead space obliteration. The flap survived completely, with no recipient or
      donor site morbidity. The length of followup was 3 months and was uneventful. The
      pedicled PMT propeller flap may be considered as a valid option for
      perineoscrotal reconstruction.

PMID- 26314391
TI  - Local control of blood flow during active hyperaemia: what kinds of integration
      are important?
AB  - The focus of this review is on local mechanisms modifying arteriolar resistance
      to match blood flow to metabolism. In skeletal muscle many local mediators are
      known, including K(+) , nitric oxide (NO), purines and prostaglandins. Each
      accounts for about 30% of the response; it is widely held that these act
      redundantly: this concept awaits systematic testing. Understanding signal
      integration also requires consideration of microvascular network morphology in
      relation to local communication pathways between endothelial and smooth muscle
      cells (which are critical for many local responses, including dilatation to
      skeletal muscle contraction) and in relation to the spread of vasodilator signals
      up- and downstream throughout the network. Mechanisms mediating the spread of
      dilatation from local to remote sites have been well studied using acetylcholine
      (ACh), but remote dilatations to contraction of skeletal muscle fibres also
      occur. Importantly, these mechanisms clearly differ from those initiated by ACh,
      but much remains undefined. Furthermore, capillaries contribute to metabolic
      dilatation as they dilate arterioles directly upstream in response to vasoactive
      agents or contraction of adjacent muscle fibres. Given the dispersed arrangement
      of motor units, precise matching of flow to metabolism is not attainable unless
      signals are initiated only by 'active' capillaries. As motor units are recruited,
      signals that direct blood flow towards these active fibres will eventually be
      supported by local and spreading responses in the arterioles associated with
      those fibres. Thus, mechanisms of integration of vasodilator signalling across
      elements of the microvasculature remain an important area of focus for new
      studies. 

PMID- 26314394
TI  - Protonation State and Hydration of Bisphosphonate Bound to Farnesyl Pyrophosphate
      Synthase.
AB  - Farnesyl pyrophosphate synthase (FPPS) catalyzes the condensation of isopentenyl
      pyrophosphate (IPP) and dimethylallyl pyrophosphate to FPP and is known to be a
      molecular target of osteoporosis drugs, such as risedronate (RIS), which is a
      nitrogen-containing bisphosphonate. The protonation states and hydration
      structure of RIS bound to FPPS were determined by neutron protein
      crystallography, which allows direct visualization of hydrogens and deuteriums.
      The structure analysis revealed that the phosphate groups of RIS were fully
      deprotonated with the abnormally decreased pKa, and that the roles of E93 and
      D264 consisted of canceling the extra negative charges upon the binding of
      ligands. Collectively, our neutron structures provided insights into the
      physicochemical properties during the bisphosphonate binding event. 

PMID- 26314395
TI  - Abnormal expression of DNA methyltransferases and genomic imprinting in cloned
      goat fibroblasts.
AB  - Somatic cell nuclear transfer (SCNT) is a useful way to produce cloned animals.
      However, SCNT animals exhibit DNA methylation and genomic imprinting
      abnormalities. These abnormalities may be due to the faulty epigenetic
      reprogramming of donor cells. To investigate the consequence of SCNT on the
      genomic imprinting and global methylation in the donor cells, growth patterns and
      apoptosis of cloned goat fibroblast cells (CGFCs) at passage 7 were determined.
      Growth patterns in CGFCs were similar to the controls; however, the growth rate
      in log phase was lower and apoptosis in CGFCs were significantly higher (P <
      0.01). In addition, quantitative expression analysis of three DNA
      methyltransferases (Dnmt) and two imprinted genes (H19, IGF2R) was conducted in
      CGFCs: Dnmt1 and Dnmt3b expression was significantly reduced (P < 0.01), and H19
      expression was decreased sixfold (P < 0.01); however, the expression of Dnmt3a
      was unaltered and IGF2R expression was significantly increased (P < 0.05).
      Finally, we used bisulfite sequencing PCR to compare the DNA methylation patterns
      in differentially methylated regions (DMRs) of H19 and IGF2R. The DMRs of H19 (P
      < 0.01) and IGF2R (P < 0.01) were both highly methylated in CGFCs. These results
      indicate that the global genome might be hypomethylated. Moreover, there is an
      aberrant expression of imprinted genes and DMR methylation in CGFCs.

PMID- 26314397
TI  - Carbamate-catalyzed enantioselective bromolactamization.
AB  - A highly facile, efficient, and enantioselective bromolactamization of olefinic
      amides was effected by a carbamate catalyst and ethanol additive. The amide
      substrates underwent N-cyclization predominantly to give a diverse range of
      enantioenriched bromolactam products containing up to two stereogenic centers. 

PMID- 26314398
TI  - Bolus size for the evaluation of masticatory performance in 8-10-year-old
      children: a pilot study.
AB  - OBJECTIVE: To study bolus-size of different foods in 8- to 10-year-olds and
      appraise if 1.7-2 g of condensation silicone (Optosil(r)) is an adequate size to
      study masticatory performance in children. METHODS: Bolus-size of seven foods
      (carrot, almonds, sausage, banana, cookie, gummy bears, raisins) (placed in
      random order on a scale) was studied in 20 children, aged 8-10 years. Children
      picked up the amount they would normally take of each, and chewed and swallowed
      it (three repetitions/each). STATISTICAL ANALYSIS: Descriptive; comparisons with
      ad hoc tests. RESULTS: There are no gender differences in bolus-size. Bolus-size
      was constant but different for each food.There is no pattern of bolus-size
      depending on hardness. Bolus-size was largest for banana; smallest foralmonds.
      Bite-size for carrot (food most similar to Optosil(r)) is 2.6 times larger than
      the size used for Optosil(r). DISCUSSION: The results support using this bolus
      size of the artificial-test-food to further study masticatory function in
      children.

PMID- 26314396
TI  - Rate and Clinical Presentation of Macrophage Activation Syndrome in Patients With
      Systemic Juvenile Idiopathic Arthritis Treated With Canakinumab.
AB  - OBJECTIVE: In pivotal trials, canakinumab has been shown to be effective in the
      treatment of systemic juvenile idiopathic arthritis (JIA), but reported adverse
      events have included macrophage activation syndrome (MAS). This study was
      undertaken to assess the impact of canakinumab on MAS incidence. METHODS: An
      independent MAS Adjudication Committee (MASAC), consisting of 3 of the authors,
      was convened, and a search of databases from clinical studies of canakinumab
      treatment in systemic JIA was performed using MASAC-specified adverse event terms
      to identify potential MAS events. These were then adjudicated as "probable MAS,"
      "possible MAS," or "MAS unlikely," using criteria developed by the MASAC. MAS
      rates were expressed as numbers of cases per 100 patient-years. RESULTS: Of 72
      potential MAS cases identified, 21 events (19 with canakinumab treatment; 2 with
      placebo treatment) in 19 patients were adjudicated as being probable MAS and 10
      events in 9 patients as being possible MAS. Systemic JIA was well controlled in
      the majority of canakinumab-treated patients at the time of MAS. The time period
      between initiation of canakinumab treatment and onset of MAS ranged from 3 to
      1,358 days (median 292 days). When the rates of probable MAS events were compared
      between canakinumab-treated patients (2.8 per 100 patient-years) and placebo
      treated patients (7.7 per 100 patient-years), the difference was not significant
      (-4.9 [95% confidence interval -15.6, 5.9]). There were 3 deaths due to MAS
      related complications (2 in patients receiving canakinumab; 1 in a patient
      receiving placebo); full recovery was reported in all other patients. Infections
      were the most common trigger of MAS, and the clinical features of MAS were not
      modified by canakinumab. CONCLUSION: Canakinumab does not have a significant
      effect on MAS risk or its clinical features in patients with systemic JIA.
      Infections are the most common trigger, and MAS occurs even in patients whose
      systemic JIA is well controlled with this treatment.

PMID- 26314399
TI  - Preparation and characterization of a microencapsulated polyethylene glycol cross
      linked polyhemoglobin.
AB  - Many complications are associated to the therapeutic use of blood, among which
      are not only transfusion adverse events but also other issues such as lack of
      donors and high costs for collecting, testing, preserving, and distributing blood
      packages. Therefore, a clinically viable "blood substitute" is considered the
      holy grail of traumatology and may greatly benefit medicine. One of the most
      successful approaches to date is conjugating hemoglobin with polyethylene glycol
      (PEG). This conjugation aims mainly at overcoming free cell hemoglobin toxicity,
      which makes its use as oxygen carrier in pure form unfeasible. To improve PEG
      hemoglobin conjugates feasibility, we propose applying dual functional PEG cross
      linking hemoglobin molecules encapsulated by a protein carrier. The new oxygen
      carrier showed mean values of the hydrodynamic diameter, dispersity, and zeta
      potential of 1370 nm, 0.029 and -36 mV, respectively, evidencing the successful
      synthesis of PEG bis(N-succinimidyl succinate) and polyhemoglobin as well as the
      structuring of protein carrier. 

PMID- 26314400
TI  - Biotransformation of lysine into cadaverine using barium alginate-immobilized
      Escherichia coli overexpressing CadA.
AB  - In this study, Escherichia coli cells overexpressing lysine decarboxylase (CadA)
      were used for cadaverine production. Barium alginate was selected as a matrix for
      immobilization of E. coli YH91. Free cells and immobilized cells (IC) were
      characterized for their physiochemical properties, and the optimum pH and
      temperature were determined as 6 and 37  degrees C, respectively. Immobilized
      cells were three times more thermally stable compared to free cells at the
      optimum temperature and had a half-life (t 1/2) of 131 h. The free cells lost
      most of lysine decarboxylase activity after nine cycles, but in contrast
      immobilized cells retained 56% of their residual activity even after the 18th
      cycle. The immobilized cells gave a maximum production of cadaverine (75.8 g/L)
      with 84% conversion.

PMID- 26314401
TI  - Changes in retinal vessels related to varicocele: a pilot investigation.
AB  - The aim of this study was to investigate whether retinal vasculature changes had
      occurred (retinal artery diameter, retinal vein diameter and artery/vein ratio)
      in patients with varicocele. This pilot study included 50 healthy subjects with
      any eye disease apart from slight refractive errors and 55 patients with
      varicocele. Retinal arteriolar and venular diameters were measured and summarised
      as central retinal arteriolar equivalent (CRAE) and central retinal venular
      equivalent (CRVE). Retinal microvascular diameters and the arteriolar-to-venular
      ratio (AVR) were assessed with a digital retinal camera. All measurements and
      calculations were performed using a computer-based program. The mean CRAE value
      was 151.8 +/- 3.6 MUm in the study group and 150.4 +/- 4.5 MUm in the control
      group. Mean CRVE value was 209.4 +/- 5.9 MUm in the study group and 200.1 +/- 8.7
      MUm in the control group. AVR was found 0.72 +/- 0.02 in the study group and 0.75
      +/- 0.03 in the control group. There were significant differences between groups
      in terms of CRVE and AVR. There were no significant differences between groups in
      terms of CRAE. The results of this study showed that the patients with varicocele
      showed significant changes on retinal vascular diameter. 

PMID- 26314403
TI  - Malaria knowledge, attitudes and practices among migrants from malaria-endemic
      countries in Evrotas, Laconia, Greece, 2013.
AB  - Following re-emergence of malaria in Evrotas, Laconia, in 2009-12, a malaria
      control programme was implemented in 2011-12 targeting migrants from malaria
      endemic countries, including house-to-house active case detection, health
      education and distribution of mosquito protection items. In June 2013, we
      surveyed migrants in Evrotas to assess their malaria knowledge, attitudes and
      practices to guide prevention activities. We selected participants using simple
      random sampling and interviewed them, using structured questionnaires. We defined
      mosquito protection practices (MPPs) as the use of full-length clothes/topical
      repellent, mosquito screens, fans or air-conditioning, and insecticides. We
      calculated prevalence ratios (PRs) using Poisson regression and we allowed for
      clustering of participants in a residence. Of 654 migrants, we invited 132 and
      130 participated (all men; 120 (92%) from Pakistan). Of the 130, 56 (43%)
      identified fever as a malaria symptom; those who were aware of this had higher
      level of education (PR: 3.2; 95% confidence interval (CI): 1.2-9.0). A total of
      111 (85%) used insecticide-treated bednets and 95 (73%) used more than two MPPs.
      Poor housing conditions (warehouses/shacks: PR: 0.8; 95% CI: 0.6-0.9), were
      associated with use of up to two MPPs. Despite extensive interventions in
      Evrotas, the level of malaria awareness among migrants remained suboptimal and
      poor housing conditions hindered effective mosquito protection. We recommend
      culturally adapted health education and improvement of housing conditions to
      minimise the risk of new cases and re-establishment of malaria in Greece.

PMID- 26314402
TI  - Critical early thrombolytic and endovascular reperfusion therapy for acute
      ischemic stroke victims: a call for adjunct neuroprotection.
AB  - Today, there is an enormous amount of excitement in the field of stroke victim
      care due to the recent success of MR. CLEAN, SWIFT PRIME, ESCAPE, EXTEND-IA, and
      REVASCAT endovascular trials. Successful intravenous (IV) recombinant tissue
      plasminogen activator (rt-PA) clinical trials [i.e., National Institute of
      Neurological Disorders and Stroke (NINDS) rt-PA trial, Third European Cooperative
      Acute Stroke Study (ECASSIII), and Third International Stroke study (IST-3)] also
      need to be emphasized. In the recent endovascular and thrombolytic trials, there
      is statistically significant improvement using both the National Institutes of
      Health Stroke Scale (NIHSS) and the modified Rankin Score (mRS) scale, but
      neither approach promotes complete recovery in patients enrolled within any
      particular NIHSS or mRS score tier. Absolute improvement (mRS 0-2 at 90 days)
      with endovascular therapy is 13.5-31 %, whereas thrombolytics alone also
      significantly improve patient functional independence, but to a lesser degree
      (NINDS rt-PA trial 13 %). This article has 3 main goals: (1) first to emphasize
      the utility and cost-effectiveness of rt-PA to treat stroke; (2) second to review
      the recent endovascular trials with respect to efficacy, safety, and cost
      effectiveness as a stroke treatment; and (3) to further consider and evaluate
      strategies to develop novel neuroprotective drugs. A thesis will be put forth so
      that future stroke trials and therapy development can optimally promote recovery
      so that stroke victims can return to "normal" life. 

PMID- 26314404
TI  - Incidence and seroprevalence of tularaemia in Finland, 1995 to 2013: regional
      epidemics with cyclic pattern.
AB  - We studied the incidence of reported tularaemia by year and region and the
      prevalence of antibodies against Francisella tularensis in the adult general
      population in Finland. Moreover, we assessed the correlation between vole
      population cycles and human tularaemia outbreaks. The seroprevalence study made
      use of serum samples from a nationwide population-based health survey (Health
      2000). The samples of 1,045 randomly selected persons, representative for the
      Finnish population in each region, were screened with an enzyme-linked
      immunosorbent assay (ELISA) for the presence of IgG antibodies against F.
      tularensis, and positive results were further confirmed by immunoblotting. A
      serological response to F. tularensis was found in 2% (95% confidence interval:
      1.1-3.5) of the population. Incidence and seroprevalence were highest in the same
      areas, and vole population peaks clearly preceded tularaemia outbreaks one year
      later.

PMID- 26314405
TI  - Letter to the editor: There is a need to consider all respiratory viruses in
      suspected mumps cases.

PMID- 26314407
TI  - Evaluating the role of admixture in cancer therapy via in vitro drug response and
      multivariate genome-wide associations.
AB  - AIM: We investigate the role of ethnicity and admixture in drug response across a
      broad group of chemotherapeutic drugs. Also, we generate hypotheses on the
      genetic variants driving differential drug response through multivariate genome
      wide association studies. METHODS: Immortalized lymphoblastoid cell lines from
      589 individuals (Hispanic or non-Hispanic/Caucasian) were used to investigate
      dose-response for 28 chemotherapeutic compounds. Univariate and multivariate
      statistical models were used to elucidate associations between genetic variants
      and differential drug response as well as the role of ethnicity in drug potency
      and efficacy. RESULTS & CONCLUSION: For many drugs, the variability in drug
      response appears to correlate with self-reported race and estimates of genetic
      ancestry. Additionally, multivariate genome-wide association analyses offered
      interesting hypotheses governing these differential responses.

PMID- 26314408
TI  - Tinea Imbricata in an Italian Child and Review of the Literature.
AB  - Tinea imbricata is a chronic superficial mycosis caused by Trichophyton
      concentricum. It is characterized by widespread, annular, concentric, squamous
      lesions. Tinea imbricata is endemic in three geographical areas: Southwest
      Pacific, Southeast Asia, and Central and South America. Tinea imbricata in
      travelers returning from endemic areas is exceptionally rare. We report a case of
      tinea imbricata in an Italian child who acquired the infection during a trip to
      Solomon Islands. Three cultures were positive for T. concentricum. The patient
      was successfully treated with griseofulvin and terbinafine cream. 

PMID- 26314409
TI  - Association of APC I1307K and E1317Q polymorphisms with colorectal cancer among
      Egyptian subjects.
AB  - Colorectal cancer is a multifactorial disease that involves both environmental
      and genetic factors. The gene encoding adenomatous polyposis coli (APC) has been
      reported to be associated with colorectal cancer (CRC) risk in several ethnic
      populations. The aim of this work is to assess the association of the APC I1307K
      and E1317Q polymorphisms with CRC risk among Egyptian subjects. This study
      included 120 unrelated CRC Egyptian patients who were compared to 100 healthy
      controls from the same locality. For all subjects, DNA was genotyped for APC
      I1307K and E1317Q polymorphisms using the PCR-ARMS technique. The frequency of
      APC I1307K carrier (TA+AA genotypes) was noted to be significantly higher among
      cases with CRC compared to controls (18.3 vs. 9.0 %, OR 2.58, 95 % CI 1.09-6.09,
      p = 0.03). Also the frequency of the APC I1307K A allele was significantly higher
      among cases compared to controls (10.4 vs. 4.5 %, OR 2.47; 95 % CI 1.12-5.42, p =
      0.03). On the contrast, the frequencies of APC E1317Q GC genotype and C allele
      showed no significant difference among CRC patients compared to controls (3.3 vs.
      2.0 %, OR 1.69; 95 % CI 0.30-9.42, p = 0.69 and 2.1 vs. 1.0 %, OR 2.11; 95 % CI
      0.40-10.97, p = 0.46, respectively). Cases of the APC I1307K and E1317Q carriers
      (TA+AA and GC) showed no significant difference compared to those with I1307K and
      E1317Q non-carriers (TT and GG) regarding their clinical and laboratory markers.
      APC I1307K variant was associated with an increased risk of CRC among Egyptian
      subjects.

PMID- 26314410
TI  - Antibody-based immunotherapy of solid cancers: progress and possibilities.
AB  - Monoclonal antibodies remain a primary product option for novel cancer treatment.
      The properties of an antibody are a function of the antigen specificity and
      constant region incorporated. The rapid advance in molecular understanding of
      cancer biology and the host-tumor interaction has defined a new range of targets
      for antibody development. The clinical success of the checkpoint inhibitors has
      validated immune modulation and mobilization as a therapeutic approach. Solid
      cancers are distinguished from hematologic malignancies because the solid tumor
      stroma contains significant tumor promoting and immune dampening elements less
      prominent in hematologic cancer. This review highlights how engineered monoclonal
      antibody products are emerging as potential cornerstones of new more personalized
      cancer treatment paradigms that target both tumor and the stromal environment. 

PMID- 26314412
TI  - Effects of radiation therapy on the structure and function of the pelvic floor
      muscles of patients with cancer in the pelvic area: a systematic review.
AB  - PURPOSE: Radiation therapy (RT) is often recommended in the treatment of pelvic
      cancers. Following RT, a high prevalence of pelvic floor dysfunctions (urinary
      incontinence, dyspareunia, and fecal incontinence) is reported. However, changes
      in pelvic floor muscles (PFMs) after RT remain unclear. The purpose of this
      review was to systematically document the effects of RT on the PFM structure and
      function in patients with cancer in the pelvic area. METHODS: An electronic
      literature search using Pubmed Central, CINAHL, Embase, and SCOPUS was performed
      from date of inception up to June 2014. The following keywords were used:
      radiotherapy, muscle tissue, and pelvic floor. Two reviewers selected the studies
      in accordance with Preferred Reporting Items for Systematic Reviews and Meta
      Analyses Statement (PRISMA). Out of the 369 articles screened, 13 met all
      eligibility criteria. The methodological quality was assessed using the QualSyst
      scoring system, and standardized mean differences were calculated. RESULTS:
      Thirteen studies fulfilled all inclusion criteria, from which four were of good
      methodological quality. One presented strong evidence that RT affects PFM
      structure in men treated for prostate cancer. Four presented high-level evidence
      that RT affects PFM function in patients treated for rectal cancer. Meta-analysis
      was not possible due to heterogeneity and lack of descriptive statistics.
      CONCLUSION: There is some evidence that RT has detrimental impacts on both PFMs'
      structure and function. IMPLICATIONS FOR CANCER SURVIVORS: A better understanding
      of muscle damage and dysfunction following RT treatment will improve pelvic floor
      rehabilitation and, potentially, prevention of its detrimental impacts.

PMID- 26314413
TI  - Effects of 12-week supervised treadmill training on spatio-temporal gait
      parameters in patients with claudication.
AB  - The purpose of the study was to evaluate selected temporal and spatial gait
      parameters in patients with intermittent claudication after completion of 12-week
      supervised treadmill walking training. The study included 36 patients (26 males
      and 10 females) aged: mean 64 (SD 7.7) with intermittent claudication. All
      patients were tested on treadmill (Gait Trainer, Biodex). Before the programme
      and after its completion, the following gait biomechanical parameters were
      tested: step length (cm), step cycle (cycle/s), leg support time (%), coefficient
      of step variation (%) as well as pain-free walking time (PFWT) and maximal
      walking time (MWT) were measured. Training was conducted in accordance with the
      current TASC II guidelines. After 12 weeks of training, patients showed
      significant change in gait biomechanics consisting in decreased frequency of step
      cycle (p < 0.05) and extended step length (p < 0.05). PFWT increased by 96% (p <
      0.05). MWT increased by 100% (p < 0.05). After completing the training, patients'
      gait was more regular, which was expressed via statistically significant decrease
      of coefficient of variation (p < 0.05) for both legs. No statistically
      significant relation between the post-training improvement of PFWT and MWT and
      step length increase and decreased frequency of step cycle was observed (p >
      0.05). IMPLICATIONS FOR REHABILITATION: Twelve-week treadmill walking training
      programme may lead to significant improvement of temporal and spatial gait
      parameters in patients with intermittent claudication. Twelve-week treadmill
      walking training programme may lead to significant improvement of pain-free
      walking time and maximum walking time in patients with intermittent claudication.

PMID- 26314411
TI  - [Treatment concept for a traumatic lesion of the prepatellar bursa].
AB  - OBJECTIVE: Rapid recovery of the skin and soft tissue of the affected knee joint
      with surgical debridement of the wound and gentle, as well as risk-balanced
      partial resection of the traumatic lacerated prepatellar bursa. Functional
      aftercare with directed administration of antibiotics only. INDICATIONS: Acute,
      traumatic laceration of the prepatellar bursa. CONTRAINDICATIONS: Heavy
      contamination of the wound. Large, not closable skin defect or deep abrasion.
      Preexisting local infection. Additional fracture of the patella. Limited
      patient's cooperation, e. g., alcohol addiction or dementia. SURGICAL TECHNIQUE:
      Subdermal application of local anesthesia through the exposed wound margins.
      Exploration of the wound and excision of the wound margins. Dissection of the
      boundary layer between the bursa and the subcutaneous fat. Debridement of the
      wound and excision of the bruised and contaminated bursa tissue. Repetitive
      rinsing. Insertion of loop drainage. Single-layer wound closure. Crepe bandage.
      POSTOPERATIVE MANAGEMENT: Crepe bandage until the first wound inspection. Wound
      inspection on postoperative day 2 with removal of the loop. Pain-adapted
      functional treatment. Antithrombotic therapy until full weight-bearing. Removal
      of the stitches on postoperative day 14. Antibiotic prophylaxis (1st generation
      cephalosporin) for immunocompromised or polymorbid patients or heavily
      contaminated wounds. RESULTS: In 2013, we treated 50 traumatic lacerations of the
      prepatellar bursa. Four had to undergo further surgical treatment after primary
      care. In two other patients, one infected and one non-infected wound healing
      complication developed, which could be treated conservatively.

PMID- 26314414
TI  - Construction of a highly efficient Bacillus subtilis 168 whole-cell biocatalyst
      and its application in the production of L-ornithine.
AB  - L-Ornithine, a non-protein amino acid, is usually extracted from hydrolyzed
      protein as well as produced by microbial fermentation. Here, we focus on a highly
      efficient whole-cell biocatalyst for the production of L-ornithine. The gene
      argI, encoding arginase, which catalyzes the hydrolysis of L-arginine to L
      ornithine and urea, was cloned from Bacillus amyloliquefaciens B10-127 and
      expressed in GRAS strain Bacillus subtilis 168. The recombinant strain exhibited
      an arginase activity of 21.9 U/mg, which is 26.7 times that of wild B. subtilis
      168. The optimal pH and temperature of the purified recombinant arginase were
      10.0 and 40  degrees C, respectively. In addition, the recombinant arginase
      exhibited a strong Mn(2+) preference. When using whole-cell biocatalyst-based
      bioconversion, a hyper L-ornithine production of 356.9 g/L was achieved with a
      fed-batch strategy in a 5-L reactor within 12 h. This whole-cell bioconversion
      study demonstrates an environmentally friendly strategy for L-ornithine
      production in industry.

PMID- 26314416
TI  - Stem cells in endometrium and endometriosis.
AB  - Endometriosis is a common chronic gynecological disease that is classically
      defined by the presence of endometrial stromal and glandular tissues outside the
      uterine cavity. Pelvic pain and infertility are the nonspecific but the most
      common symptoms of the disease; however, no currently definitive treatment has
      been developed since its pathogenesis has not been completely understood.
      Currently, none of the proposed conventional theories can explain all aspects of
      endometriosis. Recent evidence supports the presence of endometrial
      stem/progenitor cells and their possible involvement in endometrial regeneration
      and differentiation. The stem cell theory is a new hypothesis which may clarify
      the underlying pathophysiologic mechanisms of endometriosis. However, this theory
      could not only account for an alternative pathogenic mechanism of endometriosis
      but could also be involved in all conventional theories. This article will review
      the evidence for the presence of endometrial stem/progenitor cells, their
      possible sources and their possible involvement in the pathogenesis of
      endometriosis. 

PMID- 26314415
TI  - Bilateral, independent juvenile nasopharyngeal angiofibroma: case report.
AB  - BACKGROUND: Juvenile nasopharyngeal angiofibroma is a benign, vascular tumour
      that primarily occurs in adolescent males. Despite its benign nature, aggressive
      growth patterns can cause potential life-threatening complications. Juvenile
      nasopharyngeal angiofibroma is normally unilateral, originating from the
      sphenopalatine artery, but bilateral symptoms can occur if a large tumour extends
      to the contralateral side of the nasopharynx. This paper presents the first
      reported case of true bilateral extensive juvenile nasopharyngeal angiofibroma
      involving clinically challenging pre-surgical planning and surgical strategy.
      CASE REPORT: A 21-year-old male presented with increasing bilateral nasal
      obstruction and discharge. Examination revealed tumours bilaterally and imaging
      demonstrated non-contiguous tumours. Pre-operative angiography showed strictly
      ipsilateral vascular supplies requiring bilateral embolisation. Radical removal
      performed as one-step, computer-assisted functional endoscopic sinus surgery was
      performed. The follow-up period was uncomplicated. CONCLUSION: This case
      illustrates the importance of suspecting bilateral juvenile nasopharyngeal
      angiofibroma in patients presenting with bilateral symptoms. Our management,
      including successful pre-operative planning, enabled one-step total removal of
      both tumours and rapid patient recovery.

PMID- 26314417
TI  - [High Mobility Group Chromosal Protein N2 Is Expected to be as A Target of
      Cellular Immunetherapy in Leukemia and Tumors].
AB  - Recently, chimeric antigen receptors T cells (CAR T) have made a breakthrough in
      the treatment of lymphoma and leukemia, open a new path for the tumor cellular
      immunetherapy. It is the key for CAR T to take the gene which can identify the
      CD19 antigen of lymphoblastic leukemia into lymphocytes, enable it to kill
      leukemia cells with specific cell-surface loci. The same principle also applies
      to other aspects, if we find specific target genes of lymphocytes. Recent studies
      have found that high mobility group protein N2 (high mobility group chromosal
      protein N2, HMGN2) is the excellent target of tumor-associated antigen in
      lymphocytes, is the antitumor effector molecule of CD8(+) T cells, which has the
      ability of trends and specific identify/binding in myeloid leukemia, breast
      cancer, cervical cancer and other tumor cells. HMGN2 is expected to be used for
      the preparation of specific identification of tumor lymphocytes and to treat more
      leukemia and tumors. This article focuses on the strucure and function of HMGN
      and the chemotaxis and antitumor effect of HMGN2 in leukemia and tumors. 

PMID- 26314418
TI  - [Expression of Notch Gene and Its Role of Anti-apoptosis and Drug-resistance of
      Cells in Chronic Lymphocytic Leukemia].
AB  - OBJECTIVE: To investigate the expression of Notch gene in chronic lymphocytic
      leukemia cells and to explore the change of Notch protein after the therapy with
      cytosine arabinoside or dexmethasone, and the mechanism of Notch mediated anti
      apoptosis and drug-resistance in chronic lymphocytic leukemia cells. METHODS: The
      mononuclear cells from bone marrow or peripheral blood of chronic lymphocytic
      leukemia patients (24 cases) and healthy donors (14 cases) were collected, then
      the expression of Notch gene, BCL-2, as well as NF-kappaB gene were detected by
      real-time fluorescent quantitative PCR (qRT-PCR) at the level of transcription.
      The change of Notch protein in L1210 cell lines after therapy with cytosine
      arabinoside and dexmethasone was determined by Western blot. RESULTS: mRNA
      expression levels of Notch1, Notch2, BCL-2 and NF-kappaB gene in CLL group were
      significantly higher than those in healthy control group (0.8556 +/- 0.8726 vs
      0.6731 +/- 0.5334, P = 0.0182; 1.2273 +/- 0.8207 vs 0.6577 +/- 0.6424, P <
      0.0001; 8.0960 +/- 7.5661 vs 0.5969 +/- 0.4976, P < 0.0001; 1.0966 +/- 0.6925 vs
      0.5373 +/- 0.7180, P < 0.0001, respectively), but no significant difference was
      found between Notch3 and Notch4 gene (1.1914 +/- 2.4219 vs 0.8713 +/- 0.7937, P =
      0.3427; 0.8174 +/- 1.0869 vs 0.9752 +/- 1.3446, P = 0.2402, respectively). Notch1
      protein expression in L1210 cells were significantly decreased after treating
      with cytosine arabinoside of low and middle concentrations, but increased after
      treating with cytosine arabinoside of high concentration or prolonging time of
      cytosine arabinoside of middle con-centration. Notch1 protein expression in L1210
      cells dereased after treating with dexamethasone, but did not be changed with the
      different concentrations and different times of dexmethason. CONCLUSION: The
      transcription level of Notch gene in CLL patients significantly higher than that
      in normal controls. The Notch1 protein expression is down-regulated in process of
      inhibiting L1210 cell proliferation by Ara-C and dexmethason. Notch signaling
      pathway may mediated anti-apoptosis and drug resistance of CLL cells. Notch
      molecule possibly plays an important role in the anti-apoptosis and drug
      resistance of CLL cells.

PMID- 26314419
TI  - [Expression of BAG3 Gene in Acute Myeloid Leukemia and Its Prognostic Value].
AB  - OBJECTIVE: To investigate the expression of BAG3 gene in acue myeloid leukemia
      (AML) and its prognostic value. METHODS: Real-time quantitative RT-PCR was used
      to detect the expression of BAG3 mRNA in 88 previously untreated AML patients.
      The corelation of BAG3 expression level with clinical characteristics and known
      prognostic markers of AML was analyzed. RESULTS: In 88 patients with AML, the
      expression of BAG3 mRNA in NPMI mutated AML patients was obviously lower than
      that in NPMI unmutated patients (P = 0.018). The expression level of BAG3 mRNA
      did not related to clinical parameters, such as age, sex, FAB subtype, WBC count,
      extra-modullary presentation, and to prognostic factors including cytogenetics,
      FLT3-ITD, c-kit and CEBPalpha mutation status (P > 0.05). The expression level of
      BAG3 had no obvious effect on complete remission (CR) of patients in first
      treatment. The expression level of BAG3 in non-M3 patients was higher than that
      in relapsed patients (P = 0.036). The expression level of BAG3 had no effect on
      overall survival (OS) of patients. CONCLUSION: The expression level of BAG3 does
      not correlated with known-prognostic markers of AML, only the expression level of
      BAG3 in NPM1 mutated patients is lower than that in NPM1 unmutated patients. The
      expression level of BAG3 has no effect on OS of AML patients, the BAG3 can not be
      difined as a prognostic marker in AML.

PMID- 26314420
TI  - [Expression of Programmed Death Ligand-1 (PD-L1) in Human Acute Leukemia and Its
      Clinical Significance].
AB  - OBJECTIVE: To explore the expression of PD-L1 in acute leukemia patients, and to
      analyze the relationship of PD-L1 expression with the patients' clinical
      characteristics and prognosis. METHODS: The expression of PD-L1 in leukemia cells
      of 75 patients including 59 de novo patients and 16 relapse/refractory patients
      with acute leukemia was detected by the flow cytometry, the clinical information
      was collected, and the therapeutic efficacy of de novo patients was analyzed.
      RESULTS: The PD-L1 was expressed in human acute leukemia cells with total
      expression rate 32% (24/75), and its expression level in AML-M5 was higher than
      that in other leukemias [56.3% (9/16) vs 25.4% (15/59)], there was statistical
      significance (P = 0.019). The PD-L1 possitive rate in relapse/refractory group
      was higher than that in de novo patient group [(56.3% (9/16) vs 25.4% (15/59)],
      and there was statistical significance (P = 0.019). In 59 de novo patients, the
      CR rate of PD-L1 positive group after 1 course of chemotherapy was lower than
      that in PD-L1 negative group (66.7% vs 71.4%), the CR rate of PD-L1 positive
      group after 2 courses of chemotherapy was also lower than that in PD-L1 negative
      group (70% vs 88.6%). The relapse rate and the proportion of refractory patients
      in PD-L1 possitive group were higher than those in PD-L1 negative group. The
      expression of PD-L1 did not correlated with the clinical parameters, such as sex,
      age, extramedullary infiltration, percentage of blast cells in bone marrow,
      counts of WBC, RBC and platelet, as well as molecular biological features and
      cytogenetical characteristics. CONCLUSION: PD-L1 is expressed in human acute
      leukemia cells, and may be involved in the immune escape and primary resistant
      mechanisms, PD-L1 may be used as an indicator for evaluation of the the patients'
      prognosis and reocurrence.

PMID- 26314421
TI  - [Expression of Insulin-like Growth Factor Binding Protein 3 in Acute Myeloid
      Leukemia and Its Clinical Significance].
AB  - OBJECTIVE: To explore the expression of insulin-like growth factor binding
      protein 3 (IGFBP3) in acute myeloid leukemia and its clinical significance.
      METHODS: Using GAPDH as internal reference, IGFBP3 gene expression was detected
      in the bone marrow mononuclear cells of 43 de novo AML patients, 36 patients with
      complete remission (CR) and 28 cases of controls by using SYBR-Green I real-time
      quantitative PCR, the differences of gene expression between the three groups
      were compared. RESULTS: IGFBP3 gene expression level in the de novo group were
      lower than that in CR group and control group (P < 0.05), but there was no
      statistically significant difference of IGFBP3 expression level in CR group and
      control group (P > 0.05). CONCLUSIONS: The IGFBP3 as a tumor suppressor gene may
      play a role in the pathogenesis of acute myeloid leukemia, its expression level
      is recovered after complete remission, therefore, IGFBP3 can be used as an
      indicator of evaluating clinical curative effect.

PMID- 26314422
TI  - [Expression of DNA Methyltransferase Genes and Its Significance in AML Patients].
AB  - OBJECTIVE: To detect the expression of DNA methyltransferases (DNMT) mRNA in the
      patients with acute myelogenous leukemia (AML) and to analyze the retationship
      between the mRNA expression of DNMT and cellular and moleculogenetic risk
      stratifieation in AML patients, and to evaluate the role of the DNMT mRNA
      expression in AML prognosis and clinical treatment. METHODS: The mRNA expression
      of DNMT was detected by real-time PCR in 123 AML patients and 20 healthy people.
      RESULTS: the mRNA expression levels of DNMT were lower in the healthy people and
      higher in AML patients; the mRNA expression levels of DNMT in the patients after
      the consolidation therapy were lower than that in the patients of initial
      diagnosis and replapse; The mRNA expression levels of DNMT did not correlate with
      age, sex and the clinical characteristics at initial diagnosis, such as white
      blood cell count, FAB classification and chromosomal karyotype in AML patients.
      In CR patients after standard treatment, the initial mRNA expression level of
      DNMT3b was higher. Based on cellular and moleculogenetic risk stratificantion,
      the DNMT expression level in the intermediate risk AML patients was higher.
      CONCLUSION: The mRNA expression of DNMT may play an important role in AML
      pathogenesis and can serve as an index for evaluating AML prognosis and for
      instructing clinical treatment.

PMID- 26314423
TI  - [Expression of Gli1 in Adult Acute Lymphoblastic Leukemia and Its Clinical
      Significance].
AB  - OBJECTIVE: To explore the expression and clinical significance of Hedgehog
      signaling transcription factor Gli1 in acute lymphoblastic leukemia (ALL)
      patients. METHODS: The clinical specimens were obtained from 32 newly diagnosed
      and 6 relapsed ALL patients. Normal bone marrow cells from 15 healthy donors were
      used as controls. Real-time qPCR and Western blot were applied to detect Gli1
      mRNA and protein expression in bone marrow mononuclear cells (BMMNC) of these
      samples respectively. The relation of Gli1 mRNA levels with clinical parameter
      was also evaluated. RESULTS: The expression level of Gli1 mRNA in de novo and
      relapsed ALL patients was significantly higher than that in the normal controls
      (P < 0.05). There was no stalistically significant difference of the Gli1 mRNA
      expression between de novo and relapsed ALL cases (P > 0.05). In 24 de novo ALL
      patients with complete remission (CR) after induction chemotherapy, the levels of
      Gli1 mRNA were significantly reduced as compared with levels before treatment (P
      < 0.05). However, in 4 ALL patients without remission, no obvious difference of
      Gli1 mRNA levels were observed as compared with levels of Gli1 before treatment
      (P > 0.05). A positive correlation between the Gli1 mRNA expression level and
      white blood cell count (WBC) was found in the BMMNC of ALL patients (R = 0.725, P
      < 0.05). Similarly, Gli1 protein expression was significantly higher in the de
      novo and relapsed ALL cases compared with normal controls. The Gli1 protein level
      was down-regulated when the ALL patients was in CR. CONCLUSION: The expression of
      Gli1 mRNA and protein has been found to be high in de novo and relapsed ALL
      patients, and the change of Gli1 expression maybe relate to therapeutic efficacy
      and prognosis of ALL patients.

PMID- 26314424
TI  - [Effect of ADAM10 Inhibitor GI254023X on Proliferation and Apoptosis of Acute T
      Lymphoblastic Leukemia Jurkat Cells In Vitro and Its Possible Mechanisms].
AB  - OBJECTIVE: To investigate the effect of ADAM10 inhibitor GI254023X on the
      proliferation and apoptosis of acute T-lymphoblastic leukemia Jurkat cells and
      its mechanisms. METHODS: Jurkat cells were treated with different concentrations
      of GI254023X, the proliferation-inhibition curve was assayed and plotted by CCK-8
      method, the cell viability and apoptosis was detected by flow cytometry with
      Annexin V and 7-AAD staining, the cleavage of Notch1 protein was determined by
      Western blot, the transcripts of anti-apoptotic genes BCL-2, MCL-1, BCL-xl and
      Notch1 target gene Hes-1 were detected by real-time PCR. RESULTS: The GI254023X
      obviously inhibited the proliferation of Jurkat cells in concentration-dependent
      manner. As compared with the control group, the apoptosis of cells increased
      along with increment of GI254023X concentration. Compared with control group, the
      expression of Cleaved Notch1 was down-regulated while the expression of Notch1
      was up-regulated in a time-dependent manner after the treatment with GI254023X.
      The levels of MCL-1 and Hes-1 mRNA transcripts in Jurkat cells were reduced in
      GI254023X treated group, but did not show obvious effect on the level of BCL-2
      and BCL-xl mRNA transcripts. CONCLUSION: GI254023X can remarkably inhibit
      proliferation and induce apoptosis of Jurkat cells. The inhibition of Notch1
      activation and the down-regulation of apoptosis-related gene MCL-1 may be
      involved in the process of apoptosis.

PMID- 26314425
TI  - [Effects of Garcinia Acid Combined with Daunorubicin on Expression of Pregnane X
      Receptor in Leukemia Cell Line K562/A02].
AB  - OBJECTIVE: To explore the expression of PXR (Pregnane X receptor) in several
      malignant hematological cell lines, and to investigate the reversal effect of
      Gambogic acid (GA) on multi-drug resistance (MDR) of K562/A02 cell line and its
      reversal mechanism. METHODS: Transcription of PXR was detected by real-time PCR
      in several malignant hematological cell lines. The growth inhibition rate of
      K562/A02 in different experimental groups was assayed by MTT method, and the
      expression of PXR protein was measured by Western blot. RESULTS: PXR gene
      transcription could be detected in several hematological malignancy cell lines,
      and it was significantly higher in K562/A02 cell line, compared with the other
      cell lines used in this experiment. Low-dose GA could enhance cell growth
      inhibition rate, increasing the effect of chemotherapy, which may be associated
      with down-regulation of PXR expression. PXR gene transcription and protein
      expression in GA and DNR+GA groups decreased as compared with control group and
      the DNR group, suggesting that low-dose GA can down-regulate PXR gene
      transcription and protein expression. CONCLUSION: PXR gene transcription can be
      detected in several hematological malignancy cell line, which is significantly
      higher in K562/A02 cell line, as compared with the other cell lines used in this
      experiment. Low-dose GA can enhance cell growth inhibition rate, increasing the
      effect of chemotherapy, which may be associated with down-regulation of PXR
      expression.

PMID- 26314426
TI  - [Preparation and Assessment of IL1RAP Monoclonal Antibody].
AB  - OBJECTIVE: To prepare and identify human monoclonal antibody against IL-1
      receptor accessory protein (IL1RAP), which is a new identified surface marker for
      leukemia stem cells (LSC). METHODS: BALB/c mice were inoculated intraperitoneally
      with hybridoma cells (3H6E10, 10D8A7) and their ascites were collected. The
      monoclonal antibody against hu-IL1RAP specifically was purified from ascites, the
      nondenaturing-PAGE, ELISA and Western blot were used to detect the purity, titer
      and sensitivity of antibody. RESULTS: Two purified antibodies were obtained and
      named as 3H6E10 McAb and 10D8A7 McAb, whose purity was 95% and 94% respectively.
      The titer of two purified monoclonal antibodies was 1 : 81000 and specific
      conjugation of IL1RAP purified protein and endogenous protein from normal people
      and leukemia patients with purified antibodies were confirmed. CONCLUSION: The
      purified monoclonal antibodies which can specifically bind to hu-IL1RAP are
      successfully prepared, thus providing novel way to effectively clear LSC in the
      future.

PMID- 26314427
TI  - [Experimental Study on Apoptosis of Kasumi-1 Cells Induced by Sertraline and Its
      Molecular Mechanism].
AB  - OBJECTIVE: To investigate the biological effects of sertraline, one of
      psychotropic drugs, on actue myeloid leukemia cell line Kasumi-1. METHODS: Cells
      were treated by different concentrations of sertraline for different times. The
      effects of sertraline were evaluated by cell growth, cell morphology, cell cycle
      distribution and markers of cell apoptosis, respectively. Western blot was used
      to detect the expression change of related proteins. RESULTS: Sertraline could
      inhibit cell proliferation and induce apoptosis. After treatment with 15 umol/L
      and 20 umol/L sertraline for 24 h, the inhibitory rate of Kasumi-1 cell
      proliferation was (19.00 +/- 7.37)% and (47.90 +/- 11.19)%, respectively.
      Meanwhile, compared with the control group, the percentage of Annexin V positive
      cells in Kasumi-1 cells treated with sertraline for 24 h raised obviously from
      (9.71 +/- 2.12)% to (20.54 +/- 2.52)% and (45.37 +/- 7.88)% (P < 0.01),
      respectively. The cells were arrested in G0/G1 and G2/M phase. In addition, it
      was found that sertraline could also down-regulate the level of translationally
      controlled tumor protein (TCTP) in Kasumi-1 cells. CONCLUSION: Sertraline can
      significantly induce the apoptosis of Kasumi-1 cells, that probably is associated
      with the down-regulation of TCTP protein expression.

PMID- 26314428
TI  - [Effect of As2O3on Hedgehog Pathway in Chronic Myeloid Leukemia Cells].
AB  - OBJECTIVE: To explore the effect of As2O3on Hedgehog pathway in chronic myeloid
      leukemia (CML) cells. METHODS: The apoptosis of K562 cells was detected by MTT
      method and flow cytometry; the expressions of PTCH and SMO protein and mRNA in
      Hedgehog pathway were determined by Western blot and real-time PCR, respectively.
      Retults: The As2O3 could induce the apoptosis of K562 cells with optimal
      concentration 2 umol/L and optimal time 24 hours. The expressions of PTCH and SMO
      protein and mRNA in Hedgehog pathway of K562 cells treated with As2O3at optimal
      concentration and optimal time were down-regulated. CONCLUSION: The As2O3can down
      regulate the expression of PTCH and SMO in Hedgehog pathway.

PMID- 26314429
TI  - [Effect of Recombinant Adenovirus AdE-SH2-Caspase 8 on the Apoptosis of Imatinib
      resistant K562/G01 Cell Line].
AB  - OBJECTIVE: To investigate the effect of SH2-Caspase 8 fusion protein expressed by
      recombinant adenovirus AdE-SH2-Caspase8-HA-GFP (SC) on the apoptosis of K562/G01
      cell line, which is a BCR/ABL positive chronic myeloid leukemia cell line and
      resistant to imatinib. METHODS: The K562/G01 cell line was infected with AdE-SH2
      Caspase 8-HA-GFP adenovirus (SC), then the cells were divided into 3 groups: AdE
      SH2m-Caspase 8-HA-GFP (SmC) group, AdE-GFP (CMV) group and PBS group as control.
      The infection efficiency was observed under fluorescent microscopy and by flow
      cytometry. The expression of fusion protein SH2-Caspase 8-HA was measured by
      Western blot. The morphology of the cells detected by Wright's staining. The
      apoptosis of the cells were detected by flow cytometry and DNA ladder. The
      expression of Caspase 3 and PARP were detected by Western blot. RESULT: The
      infection efficiency of SC on K562/G01 cells was high which was confirmed by
      fluorescent microscopy and FCM. SH2-Caspase 8-HA fusion protein were expressed
      correctly in K562/G01 cells. After treatment with SC the apoptosis of K562/G01
      cells could be observed by microscopy. The result of FCM showed that early
      apoptosis of K562/G01 cells increased significantly as compared with control
      groups (P < 0.05). DNA ladder showed that the classic DNA ladders appeared in
      K562/G01 cells after treatment with SC. The wester blot detection showed that the
      expression level of apoptosis-related protein Caspase 3 and PARP increased.
      CONCLUSION: The recombinant adenovirus SC expressing SH2-Caspase 8 fusion protein
      can induces the apoptosis of K562/G01 cells.

PMID- 26314430
TI  - [Efficacy of Donor Lymphocyte Infusion for Treating Relapsed High-Risk Leukemia
      patients after Allogeneic Hematopoietic Stem Cell Transplantation].
AB  - OBJECTIVE: To investigate the efficacy of donor lymphocyte infusion (DLI) for
      treating relapsed high-risk leukemia patients after allogeneic hematopoietic stem
      cell transplantation (allo-HSCT). METHODS: The data of 15 leukemia patients who
      had received DLI and 13 leukemia patients who had not received DLI in Zhujiang
      Hospital from 2000 to 2014 were studied retrospectively, and their 1 and 3 year
      overall survival rate (OS) were compared between the two groups. RESULTS: In 15
      patients received DLI, the 1 and 3 year OS were 58.3% and 46.7%, the 1 and 3 year
      disease-free survival (DFS) were 22.0% and 11.0%, respectively. The main death
      cause in these patients included relapse (n = 5) and acute GVHD (n = 1), whereas
      in 13 patients who had not received DLI, the 1 and 3 year OS were 29.9% and 15.0%
      respectively, their 1 year DFS were 11.2%. The main death cause in these patients
      were relapse (n = 9). The 1 and 3 year OS of patients who had received DLI was
      higher as compared with the patients who had not received DLI. but this
      difference was no statistically significant (P = 0.069). CONCLUSION: DLI is an
      effective method for treating patients with relapsed leukemia, and may improve
      the therapeutic efficacy of DLI by combining other methods or alternating the
      types of the donor lymphocytes.

PMID- 26314431
TI  - [Effect of PKF118-310 on Cell Cycle and Proliferation of K562 Cells and Its
      Mechanism].
AB  - Objetive: To investigate the effects of PKF118-310 on cell cycle and
      proliferation of K562 cell lines and its mechanism. METHODS: After treatment of
      PKF118-310 with different concentration, the proliferation inhibition on K562
      cell lines was detected by MTT, the existance of beta-catenin and TCF-4 in the
      cells was observed by immunohistochemistry. The change of the cell cycle was
      detected by flow cytometry. The expressions of caspase-3, beta-catenin, TCF and
      BCL-9 were detected by Western blot. RESULTS: PKF118-310 can inhibit the
      proliferation of K562 cell line by S phase blocking. The beta-catenin and TCF in
      the cells were observed by immunohistochemistry. After treating this cell line
      with PKF118-310 of different concentrations for 72 h, the expression level of
      caspase-3 increased, the expression levels of beta-catenin, TCF and BCL-9
      significantly decreased. CONCLUSION: PKF118-310 induces cycle arest of K562 cells
      at the S phase and inhibits the proliferation of these cells through decreasing
      beta-catenin/TCF/BCL-9 thrascriptional activity.

PMID- 26314432
TI  - [Clinical Value of Arsenous Acid for Treating Patients with Acute Promyelocytic
      Leukemia].
AB  - OBJECTIVE: To explore the clinical value of arsenious acid (H3AsO3) for treating
      patients with acute promyelocytic leukemia (APL). METHODS: A total of 86 patients
      with APL were randomly divided into experimental group (43 cases) and control
      group (43 cases). The control group was treated by all trans retinoic acid
      combined with chemotherapy, the experimental group were treated by arsenous acid
      on the basis of the control group. RESULTS: The overall response rate (ORR) in
      experimental group (100.00%) was significantly higher than that in control group
      (88.37%) (P < 0.05). The time of returm to complete remission in experimental
      group (30.86 +/- 4.34) was better than that in control group (42.42 +/- 7.10) d
      (P < 0.05). The time of return to normal levels of peripheral WBC count (20.86 +/
      9.28) * 109/L, hemoglobin count (68.62 +/- 14.97) g/L and thrombocyte count in
      experimental group obviously less than that in control group (P < 0.05). The
      rates of high white blood syndrome (HWBS), disseminated intravascular coagulation
      (DIC) in experimental group were lower than that in control group (P < 0.05). The
      survival rates of 2 and 3 years in experimental group were higher than that in
      control group (P < 0.05). The recurrence rate after treatment in experimental
      group was lower than that in control group (P < 0.05). The application of
      arsenious acid was main factor for patients survival (P < 0.05). CONCLUSION:
      Arsenious acid can improve the clinical efficacy for the patients with acute
      promyelocytic leukemia, and reduce the complication, therefore it is worthy of
      application in clinic.

PMID- 26314433
TI  - [MiR-18a Can Regulate Chemotherapy Sensitivity of Leukemia Cell HL-60 to VP-16
      and VCR by Targeting ATM].
AB  - OBJECTIVE: To investigate the regulatory effects of miR-18a on chemotherapeutic
      sensitivity of leukemia cell HL-60 to VP-16 and VCR, and explore its molecular
      mechamism. METHODS: The HL-60 PC DNA3.1-miR-18A cell line with stably
      overexpressing miR-18a was constructed and their sensitivity to VP-16 and VCR was
      detected. The luciferase reporter vector of ATM 3'UTR region was constructed and
      the targeting effect of miR-18a on ATM was identified. The expression level of
      ATM in HL-60 cells overexpressing miR-18a was detected by Western blot. The
      seusitivity of HL-60 cells with knockdown of ATM to VP-16 and VCR was detected by
      CCK-8 method. The ATM expression level in HL-60 cells with stably overexpression
      miR-18a after transfection of miR-18a inhibitor was detected by using Western
      blot and the sensitivity changes of these HL-60 cells to VP-16 and BCR were
      detected. RESULTS: After overexpression of miR-18a, the viability of HL-60 cells
      treated with VP-16 and VCR of same concentration decreased; the detectiion of
      luciferase activity showed that the miR-18a could inhitit activity of luciferase
      reporter vector of ATM; the expression level of ATM in HL-60 cells was down
      regulated after transfection with miR-18a; the cell viability decreased when HL
      60 cells were treated with VP-16 and VCR after knockdown of ATM; the expression
      level of ATM was up-regulated and the cell viability decreased when HL-60 cells
      were treated with VP-16 and VCR after transfection with miR-18a inhibitor.
      CONCLUSION: The miR-18a can regulated the sensitivity of leukemia HL-60 cells to
      VP-16 and VCR by targeting ATM.

PMID- 26314434
TI  - [Inhibitory Effect of Curcumin on Proliferation of CD34(+) Acute Myeloid Leukemia
      Cells and Its Mechanism].
AB  - OBJECTIVE: To explore the inhibitory effect of curcumin on proliferation of
      CD34(+) acute myeloid leukemia cells and its mechamism. METHODS: KG1a and Kasumi
      1cell lines were treated with curcumin of different concentrations (0, 40, 60, 80
      umol/L). The effect of curcumin on cell viability and proliferation was detected
      by trypan blue staining and cell count. The effect of curcumin on distribution of
      NF-kappaB P65 subunit was analyzed by immunofluorescence and Western blot.
      RESULTS: The curcumin inhibited proliferation of KG1a and Kasumi-1 cells in a
      dose-dependent manner. Western blotting showed that curcumin led to significant
      down-regulation of NF-kappaB P65 nuclear protein expression. Immunofluorescence
      assay showed that treatment with 40 umol/L of curcumin for 48h suppressed the
      nuclear translocation of NF-kappaB p65 in KG1a and Kasumi-1 cells. CONCLUSION:
      The curcumin suppresses cell growth of KG1a and Kasumi-1 cells, its mechanism may
      be related to inhibitory effect of curcumin on NF-kappaB p65 nucleus protein.

PMID- 26314435
TI  - [Expression and Clinical Significance of Bmi-1 and P14 in Extranodal NK/T-cell
      Lymphoma].
AB  - OBJECTIVE: This study was aimed to investigate the expression and clinical
      significance of Bmi-1 and P14 in extranodal NK/T-cell lymphoma (ENKTCL) tissue.
      METHODS: Maxvision immunohistochemistry technique was used to detect the
      expression level of Bmi-1 and P14 in the tissues of 21 patients with ENKTCL and
      11 normal lymph nodes. The correlation of Bmi-1 or P14 expression with the
      clinical features and the correlation between Bmi-1 and P14 expression were
      analyzed. RESULTS: The expression of Bmi-1 protein was higher in tissues of
      ENKTCL than that in tissues of lymph nodes, and the Bmi-1 expression levels did
      not correlate with patients' sex, age, lactate dehydrogenase (LDH), International
      Prognostic Index (IPI) scores and B symptoms (P > 0.05), except for clinical
      stage (P < 0.05). The P14 protein expression level was lower in ENKTCL tissues
      than in normal lymph node tissues, which did not correlate with age, sex, LDH,
      IPI scores, clinical stage and B symptoms. Correlation test showed a negative
      correlation between Bmi-1 and P14 (r = -0.472, P = 0.031). CONCLUSION: Bmi-1
      protein over-expresses in ENKTCL tissues that may display a negative-regulation
      effect on P14 in the genesis and progress of ENKTCL.

PMID- 26314436
TI  - [Value of PET/CT after Chemotherapy for Evaluating Therapentic Efficacy of
      Patients with Diffuse Large B-cell Lymphoma].
AB  - OBJECTIVE: To investigate the value of PET/CT after chemotherapy for evaluating
      therapeutic efficacy of patients with diffuse large B-cell lymphoma (DLBCL).
      METHODS: (18)F-FDG PET/CT was performed before and after 6-8 cycles of
      chemotherapy in 73 newly diagnosed patients with DLBCL from September 2005 to
      January 2012. The results of pre-treatment PET/CT was compared with results of
      post-treatment PET/CT. These patients were divided into 3 groups: complete
      response group, partial response group and no response group. The post-treatment
      PET/CT results was used to assess its ability to predict progression-free
      survival (PFS) and overall survival (OS). RESULTS: The comparison of PET/CT
      results before and after chemotherapy showed that 2-year PFS rates of complete
      response group, partial response group and no response group were 82% (41/50),
      45.5% (5/11) and 8.3% (1/12), respectively; and the 3-year OS rates of 3 groups
      were 88% (44/50), 54.5% (6/11) and 8.3% (1/12) respectively (both P < 0.01). The
      2-year PFS rate and the 3-year OS rate of the complete response group and partial
      response group were significantly higher than those of no response group (both P
      < 0.05), and there was also significant statistical difference between partial
      response group and complete response group in 2-year PFS rate and 3-year OS rate
      (both P < 0.05). CONCLUSION: The post-treatment PET/CT can be accurately used to
      evaluate the curative efficacy of chemotherapy and prognosis of patients with
      DLBCL.

PMID- 26314437
TI  - [Distribution of CD45RO+ T and CD45RA+ T Cells in Peripheral Blood of Patients
      with Peripheral T Cell Lymphoma].
AB  - OBJECTIVE: To investigate the clinical significance of memory T cells (CD45RO+ T)
      and the initial T cells (CD45RA+ T) distribution in peripheral blood of patients
      with peripheral T-cell lymphoma (PTCL). METHODS: A total of 27 patients diagnosed
      as PTCL in our hospital from February 2010 to February 2014 were collected in
      this study; whereas 30 healthy people were enrolled as control. The distribution
      of CD45RO+ T and CD45RA+ T cells were detected seperately in each group, and the
      results were analysed further. RESULTS: The expression of T cell antigens in
      lymphnodes of PTCL patients were diverse: the CD4+ T cells were the main immune
      phenotype, while the B cell-related antigen was not expressed. The CD4+/CD8+,
      CD4+ CD45RO+ T in the peripheral blood of PTCL patients were significantly lower
      than that in normal group (P < 0.05); while the CD4, CD45RA+ T, CD8+ CD45RA+ T
      and CD8+ CD45RO+ T were significantly higher than that in normal group (P <
      0.05). The patients in stage I/II had higher CD4+/CD8+, CD4+ CD45RO+ T than those
      in stage III/IV (P < 0.05), whereas the CD4+ CD45RA+ T, CD8+ CD45RA+ T and CD8+
      CD45RO+ T were significantly lower than those in the stage III/IV patients (P <
      0.05). CONCLUSION: The distributions of CD45RA+ T and CD45RO+ T in PTCL patients
      are quite different, and the corresponding treatment might be adopted according
      to the different distribution of these cells, so as to improve the diagnosis and
      prognosis of PTCL.

PMID- 26314438
TI  - [Expression of MicroRNA-26a and Its Target Gene CDK6 in Extra-nodal NK/T-Cell
      Lymphoma].
AB  - OBJECTIVE: To explore the expression level of microRNA-26a and its target gene
      CDK6 in extranodal NK/T-cell lymphoma (ENKTCL) and their possible role in genesis
      and development of ENKTCL. METHODS: Real time fluorescent quantitative PCR was
      used to detect the expression level of miR-26a in tissue of 15 patients with
      ENKTCL and 10 samples of normal NK cells. Maxvision immunohistochemistry
      technique was used to detect the expression level of CDK6 and miR-26a in tissue
      of 20 ENKTCL cases, 10 cases of proliferative lymphadenitis and 10 samples of
      normal lymph node, respectively. The possible role of miR-26a and its target gene
      CDK6 in genesis and development of ENKTCL were analyzed according to the clinical
      features of ENKTCL patients. RESULTS: The expression of miR-26a was significantly
      lower in ENKTCL than that in normal NK cells. The expression of CDK6 was
      significantly higher in ENKTCL group than that in group proliferative
      lymphadenitis and normal lymph node. Correlation analysis showed that there was
      significant negative correlation between miR-26a expression and CDK6 expression
      (r = -0.54, P = 0.04). Meanwhile, there were no correlation of miR-26a expression
      with age, sex, Ann Arbor stage, LDH level, B symptoms and IPI. Although, there
      were no correlation of CDK6 expression with age, sex, LDH level and B symptoms,
      there were positive correlation of CDK6 expression with Ann Arbor stage and IPI.
      CONCLUSION: that abnormal expression of miR-26a may participate in genesis and
      development of ENKTCL through regulating the expression of its target gene CDK6.

PMID- 26314439
TI  - [Effect of Bortezomib on Proliferation, Apoptosis and SHP-2 Gene Expression of
      Lymphoma Cells].
AB  - OBJECTIVE: To investigate the effects of Bortezomib on proliferation, apoptosis
      and SHP-2 gene expression of lymphoma Jurkat cells and Raji cells. METHODS:
      Methylthiazoly tetrazolium assay (MTT) was used to observe the proliferation of
      Jurkat cells and Raji cells treated with bortezomib in different doses. Cell
      apoptosis was detected by morphological examination and flow cytometry. The level
      of SHP-2 mRNA expression before and after the treatment with bortezomib was
      measured by RT-PCR. RESULTS: Bortezomib could inhibit the proliferation of Jurkat
      and Raji cells and induce their apoptosis with time-and dose-dependent manner.
      After treatment with 5-100 nmol/L bortezomib, the expression of SHP-2 in Jurkat
      cells and Raji cells was upregulated. CONCLUSION: Bortezomib can inhibit the
      proliferation and induc the apoptosis of Jurkat and Raji cells obviously,
      upregulate the expression of SHP-2 mRNA, suggesting that the SHP-2 may
      participate in regulation of bortezomib induced apoptosis of Jurkat cells and
      Raji cells.

PMID- 26314440
TI  - [PET/CT Image Values in Clinical Staging of the Patients with Non-Hodgkin's
      Lymphoma].
AB  - OBJECTIVE: To explore the PET/CT image value in clinical staging for the patients
      with non-Hodgkin's lymphoma (NHL). METHODS: A total of 142 cases of NHL in our
      hospital from May 2012 to February 2015 were enrolled in this study. The results
      of PET/CT staging and clinical staging were compared. The staging of simple
      intranodal NHL and extranodal NHL with or without lymphonode involvement was
      analyzed. RESULTS: The clinical staging results of 142 NHL patients showed that 8
      cases were observed in I stage, 34 cases were observed in II stage, 40 cases were
      observed in III stage, 60 cases were found in IV stage; the staging results of
      PET/CT showed that 6 cases were found in I stage, 36 cases were found in II
      stage, 44 cases were found in III stage, 56 cases were found in IV stage. The
      coincidence rate of PET/CT staging with clinical staging was 95.77% (136/142).
      Comparison of PET and CT staging for simple intranodal NHL indicated no
      statistical difference (P > 0.05), while the PET and CT staging results of
      extranodal NHL with or without lymphonode involvement were statistically
      significant different (P < 0.05). CONCLUSION: The PET/CT image can accurately
      detect the involved lymphnodes and can sensitively detect the involved extranodal
      lesions. PET/CT staging has high coincidence rate with clinical staging, thereby
      it can be used to guide the clinical treatment.

PMID- 26314441
TI  - [Clinical Efficacy of L-Asparaginasum Combined with CHOP for Treating Patients
      with Extranodal Natural Killer/T Cell Lymphoma].
AB  - OBJECTIVE: To investigate the clinical efficacy of L-asparginasum, ASP) combined
      with CHOP for treating patients with extranodal natural killer/T-cell lymphoma.
      METHODS: A total of 68 patients with extranodal natural killer/T-cell lymphoma in
      our hospital from August 2007 to May 2009 were enrolled in this study, out of
      them 34 patients received CHOP regimen (CHOP group) and other 34 patients
      received CHOP regimen combined with L-Asparaginasum (ASP+CHOP group). The
      clinical efficacy of both groups was analyzed and compared after treatment.
      RESULTS: In CHOP group 16 patients achieved CR+PR, the total remission rate (TRR)
      was 47.06%; in ASP+CHOP group 24 patients achieved CR+PR, the TRR was 70.58%, and
      the TRR in ASP+CHOP group was higher than that in CHOP group, there was
      statistical significance between these 2 groups (X(2) = 3.886, P < 0.05). The
      time of PFS in CHOP group was 24.7 months, and the time of PFS in ASP+CHOP group
      was 47.5 months which was significantly longer than that in CHOP group, and there
      was statistical siguificance between these 2 groups (P < 0.05). The incidence of
      anemia with grade I-II and III-IV blood cell reduction in ASP+CHOP group was
      higher than that in CHOP group (P < 0.05). The incidence of fever with grade I-II
      and albumin decrease in ASP+CHOP group was higher than that in CHOP group (P <
      0.05). The abnormality of coagulation function in ASP+CHOP group was higher than
      that in CHOP group (P < 0.05). The anaphylactic reaction was found in 6 cases.
      The increase of serum amylase was observed in 1 case of aggressive NK/T cell
      lymphoma, the acute pancreatitis occured in 1 case who was inproved after
      treatment, but this patients died due to rapid progression of disease caused by
      poor general condition and untolerance to chemotherapy. The incomplete intestinal
      obstruction was found in 3 patients who recovered after conservative treatment.
      The grade II serum creatinine was elevated in 2 cases of ASP+CHOP group and in 1
      case of CHOP group who was inproved after symptomatic therapy. CONCLUSION: L
      Asparaginasum combined with CHOP for treating patients with extranodal natural
      killer/T-cell lymphoma is effective, and may be used in clinic.

PMID- 26314442
TI  - [Clinico-pathologic Analysis of 16 Cases of Castleman].
AB  - OBJECTIVE: To investigate the clinico-pathologic features, treatment and
      prognosis of Castleman disease. METHODS: The clinico-pathologic data of 16
      patients diagnosed as Castleman disease from January 2002 to December 2014 were
      analyzed retrospectively. RESULTS: The median age was 28.5 (7-73)years old. There
      were 14 unicentric cases, 92.8% (13/14) of which was diagnosed as hyaline
      vascular type. Two multicentric cases was diagnosed as plasmatcyic type. All the
      patients were treated by surgical resection and their median follow-up was 55.5
      (2-150)months. As a result, 13 unicentric cases achieved sustained remission, 1
      unicentric case with plasmatocytic type relapsed at 60th month after surgical
      resection. CONCLUSION: Clinical subtype and histopathogenic type are the
      dominating progonostic factors in Castleman patients. The clinical presentation
      of unicentric disease has been found to be benigns and the surgical resection can
      be used as first-line treatment method in clinic. The clinical presentation of
      multicentric disease may be stable or advanced, and the prognosis of advanced
      cases is poor as there are no effective treatments.

PMID- 26314443
TI  - [Expression of N-Cadherin in Patients with Multiple Myeloma and Its Clinical
      Significance].
AB  - OBJECTIVE: To investigate the expression of N-Cadherin in the patients with
      multiple myeloma (MM) and to explore its clinical significance. METHODS: A total
      of 64 patients with multiple myeloma were enrolled in this study. The expression
      of N-Cadherin in bone marrow CD38+/CD138+ cells from multiple myeloma patients
      was detected by flow cytometry. The relationship between N-Cadherin expression
      and clinical prognostic factors was analyzed. RESULTS: Among 64 cases of MM, the
      expression of N-Cadherin in 17 patients (26.56%) was high (> 20%), while that in
      47 cases (73.44%) was low (< 20%); The differences of N-Cadherin expression in
      disease staging and classification, known prognostic factors, myeloma cell
      antigen expression and bone damage between patients with high and low N-Cadherin
      expression were not statistically different; the difference N-Cadherin expression
      in genetic abnormalities such as D13S319 deletion, RB1 deletion and IGH gene
      rearrangement between above-methioned two groups was not significant. The 1q21
      amplification rate in the group with high expression of N-Cadherin was enhanced
      significently; the overall survival (OS) times of patients with abnormally high
      and low expression levels of N-Cadherin were 26.7 months and 55.5 months
      respectively, and the difference was statistically significant (P < 0.05).
      CONCLUSION: The high expression of N-Cadherin in multiple myeloma may be one of
      the indicator for poor prognosis of MM, which may be related with 1q21
      amplification.

PMID- 26314444
TI  - [Diagnostic Value of (18)F-FDG-PET/CT for Multiple Myeloma].
AB  - OBJECTIVE: To study the diagnostic value of (18)F-FDG-PET/CT in multiple myeloma
      (MM). METHODS: A total of 66 patients, who were highly suspected of MM in our
      hospital from July 2012 to December 2014, were chosen as study objects. All
      patients were diagnosed or excluded by pathological examination. All patients
      were detected by (18)F-FDG-PET/CT, and its diagnostic value was analyzed. The
      number of focuses were counted. RESULTS: Out of 66 patients 59 patients (89.39%)
      were diagnosed with multiple myeloma. The sensitivity of PET was 98.31%, the
      specificity of PET was 85.71%, the Youden index was 0.8402; the sensitivity of CT
      was 96.61%, the specificity of CT was 85.71%, the Youden index was 0.8232; the
      sensitivity of PET/CT was 100.00%, the specificity of PET/CT was 83.33%, the
      Youden index was 0.8333. In 59 MM patients, 635 focuses were detected, out of
      them 572 focuses (90.08%) were detected by CT, 593 focuses (93.39%) were detected
      by PET, 530 focuses (83.46%) were coincided on PET/CT. CONCLUSION: (18)F-FDG
      PET/CT has diagnostic value for multiple myeloma, and it can be used in locating
      and counting focuses, as well as in evaluating the treatment efficacy and guiding
      the clinical work.

PMID- 26314445
TI  - [Significance of Simultaneous Analysis of Bone Marrow Smear and Bone Marrow
      Biopsy in the Diagnosis of Multiple Myloma].
AB  - OBJECTIVE: To explore the value of bone marrow smear and biopsy simultaneously
      applied to diagnosis of multiple myloma (MM). METHODS: Clinical data of 30 cases
      of multiple myloma were collected from our hospital in the year 2014 and analyzed
      retrospectively, and the results of the bone marrow smear and the simultaneous
      bone marrow biopsy were compared. RESULTS: Hyperplasia levels in bone marrow
      biopsy was significantly higher than that in bone marrow smears, and the active
      and highly active hyperplasia of nucleated cells were observed in all the bone
      marrow biopsies; the myeloma cells showed a focal or diffuse distribution, the
      binuclear or polynuclear myeloma cells were observed in 22 patients (73%), but
      the detection rate of abnormal myeloma cells was 40% in bone marrow smear (P <
      0.05). There was mild to moderate hyperplasia of fibrous tissue in bone marrow
      biopsy, and the hyperplasia degeree of fibrous tissue strongly positively
      correlated with the myeloma cell ratio (r = 0.412). CONCLUSION: The bone marrow
      smear and aspiration biopsy can complement each other so as to reduce the
      misdiagnosis rate, therefore contributes to the early diaglosis and treatment.

PMID- 26314446
TI  - [Clinical Efficacy of Decitabine Combined with CAG Regimen for Myelodysplastic
      Syndrome-RAEB and Refractory Acute Myeloid Leukemia].
AB  - OBJECTIVE: To investigate the therapeutic efficacy and side effects of treating
      patients with myelodysplastic syndrome-RAEB (MDS-RAEB) and with refractory acute
      myeloid leukemia (AML) by using decitabine combined with CAG regimen. METHODS:
      Clinical data of 21 patients with MDS-RAEB or refractory AML from July 2011 to
      July 2014 were analyzed retrospectively. Among 21 patients there were 4 cases of
      MDS-RAEB and 17 cases of refractory AML; 12 cases were beyond 60 years old; 13
      cases had high-risk karyotypes. All the patients received decitabine combined
      with CAG regimen consisting of decitabine 20 mg/(m(2) . d), d 1-5; aclarubicin 10
      mg/d, d 6-13; cytarabine 20 mg/d, d 6-19; G-CSF 300 ug/d, d 6-19. RESULTS: After
      1 cycle of treatment with DCAG regimen, the outcome of 21 patients showed that 8
      cases achieved complete remission (42.1%), 8 cases achieved partial remission
      (42.1%), 2 cases achieved hematologic improvement, 1 cases achieved non-remission
      and 2 cases died; and the 1 year overall survival rate was 67.5%. The outcome of
      12 patients beyond 60 years old showed that 6 cases achieved complete renission
      (60%, 6/10), and the 1 year overall survival rate was 62.5%. The outcome of 13
      patients with high-risk karytype showed that 6 cases achieved complete renission
      (54.5%, 6/11), and the 1 year overall survival rate was 61.5%. The main adverse
      event was myelosuppression, and non-hematological toxicity included liver
      dysfunction and gastrointestinal tract reaction. CONCLUSION: Decitabine combined
      with CAG regimen is effective and safe for treatment of MDS-RAEB and refractory
      AML patients, which can prolong lives of patiens with refractory hematological
      diseases.

PMID- 26314447
TI  - [Analysis of Differentially Expressed Signaling Pathway Proteins in
      Myelodysplastic/Myeloproliferative Neoplasms-Unclassifiable].
AB  - OBJECTIVE: To screen signaling pathway proteins in
      myelodysplastic/myeloproliferative neoplasms-unclassifiable (MDS/MPN-U), and to
      explore the possible role of the differentially expressed signaling pathway
      proteins in pathogenesis of MDS/MPN-U. METHODS: Protein Pathway Array (PPA) was
      applied to analyze the differential expression levels of signaling pathway
      proteins in 10 patients with MDS/MPN-U and normal controls, and furthermore to
      identify the signaling pathways and network in which these proteins were analyzed
      by Ingenuity pathway analysis program. RESULTS: The expressions of 25 signaling
      proteins in MDS/MPN-U were significantly different, compared with the control
      group. Among them 15 proteins were upregulated in MDS/MPN-U patients, while 10
      proteins were downregulated. These dysregulated proteins were involved in 10
      major signaling pathways related with cell proliferation and immunity. The
      complicated interactive network was established by these proteins and pathways.
      CONCLUSION: The differentially expressed signaling proteins screened from the
      MDS/MPN-U patients by PPA might be helpful to reveal the pathogenesis of MDS/MPN
      U and to discover the therapeutic targets.

PMID- 26314448
TI  - [Regulatory Effect of Protein Disulfide Isomerase on Platelet GPIbalpha
      Ectodomain Shedding].
AB  - OBJECTIVE: This study was aimed to investigate the regulatory effect of protein
      disulfide isomerase (PDI) on platelet GPIbalpha ectodomain shedding. METHODS: The
      washed platelets were obtained from healthy volunteers. Platelets were incubated
      with PDI inhibitor bacitracin before stimulation with PMA (Phorbol-12-myristate
      13-acetate), dibucaine and collagen. The N-terminal domain of GPIbalpha in
      supernatant was detected by Western blot, the GPIbalpha expression and the
      intraplatelet ROS levels were measured by flow cytometry. RESULTS: neither GC
      content nor GPIbalpha expression was changed after the washed platelets from the
      healthy donors were incubated only with PDI inhibitor. The washed platelets were
      incubated with PDI inhibitor before stimulation with different stimulin, PMA,
      dibucaine or collagen, and then GPIbalpha was cleaved and ROS levels were
      elevated more than that in the controls. CONCLUSION: PDI participates in the
      induced GPIbalpha ectodomein shedding, and the effect of PDI in this process
      maybe depend on the change of ROS level inside platelets. These results might
      provide a new point of view for the platelet drug development.

PMID- 26314449
TI  - [Correlation of Plasma Co-stimulatory Molecules B7-H2 and B7-H3 with Platelet
      Auto-antibodies in Patients with Immune Thrombocytopenic Purpura].
AB  - OBJECTIVE: To investigate whether the plasma level of platelet auto- antibodies
      in ITP patients is related to that of co-stimulatory molecules sB7-H2 and sB7-H3.
      METHODS: A total of 61 ITP patients and 25 healthy controls from the First
      Affiliated Hospital of Soochow University from June 2012 to August 2013 were
      enrolled in this study. The expression levels of platelet auto-antibodies against
      5 glycoproteins (GPIX, GP Ib, GP IIIa, GPIIb and P-selectin) in plasma were
      detected by flow cytometric immuno-beads array, and the expression of soluable co
      stimulatory molecules sB7-H2 and sB7-H3 was measured by ELISA. RESULTS: The
      plasma levels of 5 auto-antibodies against platelet membrance glycoproteins
      significantly increased in ITP patiens (P < 0.01). Compared with healthy
      controls, sB7-H2 levels increased (P < 0.05), while the sB7-H3 level did not
      significantly change (r = 0.13, P > 0.05). However, the correlation analysis
      showed that sB7-H3 negatively correlated with platelet P-selectin auto-antibody
      (r = -0.46, P < 0.05), and sB7-H2 and sB7-H3 significantly reduced in ITP
      patients with positive P-selectin auto-antibody (P < 0.01). In ITP patients,
      platelet counts negatively correlated with sB7-H2 (r = -0.3907, P < 0.01), but
      did not correlate with sB7-H3. CONCLUSION: Soluble costimulatory molecule sB7-H2
      elevates in ITP patients, and the level of sB7-H3 is associated with auto
      antibodies against P-selectin, suggesting that costimulatory molecules B7-H2 and
      B7-H3 may be involved in the pathogenesis of immune regulation abnormality in
      ITP.

PMID- 26314450
TI  - [Analysis of Factors Influencing Posttransfusion Effectiveness in 26045 Cases of
      Platelet Transfusion].
AB  - OBJECTIVE: To investigate the factors influencing platelet transfusion results so
      as to improve the platelet transfusion efficiency. METHODS: According to the
      clinical symptoms (bleeding condition is stopped or improved)and the corrected
      count of increment (CCI), the patients were divided into efficient transfusion
      and inefficient transfusion groups. A total of 20 671 patients' clinical data and
      main platelet transfusion parameters in 26 045 tranfusions including platelet
      count of per- and post- transfusion, platelet component sorts, storage time and
      transfusion number were analysed. RESULTS: The comparison of platelet transfusion
      efficiency in age and sex between two groups did not showed statistical
      difference (P > 0.05), the platelet count before transfusion between two groups
      showed statistical difference (t = -5.59, P < 0.001) after converting to log, a
      significant linear correlation did not exist between storage time of the platelet
      and CCI (corrected count of increment), but there was statistical difference in
      transfusion efficiency of patients with different diseases. The patients with
      hematologic diseases showed lower efficiency of platelet transfusion. According
      to the results of Wilcocon test detection, there was difference between different
      times of transfusion and transfusion efficiency, that is to say, the transfusion
      frequency was higher, the transfusion efficency was lower. The Fisher test
      indicated that the transfusion efficiency of single platelet transfusion was
      lower than that of transfussed platelet with other blood components (P < 0.01).
      CONCLUSION: Platelet transfusion efficiency associates with many factors,
      including different diseases, whether being transfused with other blood
      components, the platelet count before transfusion, transfusion frequency, but the
      time of storage does not relate to the transfusion efficacy.

PMID- 26314451
TI  - [Protective Effect of Ulinastatin against Activation of Tourniquet-Induced
      Platelet Mitochondria Apoptotic Signaling].
AB  - OBJECTIVE: To investigate the protective effect of ulinastatin against the
      activation of tourniquet-induced platelet mitochondria apoptotic signaling.
      METHOD: 44 patients with unilateral lower limb operation and tourniquet
      application were randomly divided into normal saline group and ulinastatin group,
      and were treated with normal saline and ulinastatin respectively. 12 patents with
      unilateral lower limb operation but without tourniquet application were enrolled
      in control group. Lipid hydroperoxide (LPO) in serum was detected by LPO assay
      kit, the content of ATP was examined by fluorescein-luciferase assay kit; the
      change of mitochondrial membrane potential (Delta psim) was detected by JC-1
      mitochondrial membrane potential kit; the content of cytoplasmic cytochrome C was
      examined by Cytochrome C ELISA kit; Caspase-3 activity was detected by Caspase-3
      fluorometric assay kit. RESULTS: As compared with control group, the patients in
      normal saline group exhibited significant platelet mitochondrial dysfunction
      which characterized by low ATP level and low mitochondrial membrane potential
      (Delta psim) (P < 0.05). Tourniquet application resulted in the activation of the
      mitochondria apoptotic signaling in platelet, displaying increase in the serum
      LPO level, release of mitochondrial cytochrome C into the cytoplasm, and
      activation of caspase-3 (P < 0.05). These alterations above-mentioned were
      obviously improved by ulinastatin treatment (P < 0.05). CONCLUSION: Tourniquet
      induces platelet mitochondrial dysfunction and mitochondria-dependent apoptotic
      signaling activation, which can be improved by ulinastatin treatment.

PMID- 26314452
TI  - [Effect of Decitabine on Megakaryocyte Culture of Steroid-resistant ITP
      Patients].
AB  - OBJECTIVE: To investigate the effect of decitabine and plasma of ITP patients on
      in vitro cultrue of megakaryocytes in bone marrow of steroid-resistant ITP
      patients. METHODS: Bone marrow mononuclear cells were isolated from 20 steroid
      resistant ITP patients, both methyl cellulose semisolid culture system (to
      observe and count the number of megakaryocytes colony-forming unit) and liquid
      culture system (to analysis the expression rate of CD41a(+) cells) were used for
      megakaryocyte cultrue. The experiments were divided into 4 groups according to
      the different components of the culture system, group A was control, group B was
      added with decitabine, group C with ITP plasma, group D with both decitabine and
      ITP plasma, and the rest of the culture components were the same in the 4 groups
      except the above-mentioned materials. Morphology of megakaryocytes was observed
      by inverted and light microscopy. The expression rate of CD41a+ cells in culture
      was analysed by flow cytometric. RESULTS: Different concentration of decitabine
      showed different effect on megakaryocyte growth of steroid-resistant ITP patients
      and the optimal concentration to differentiate into megakaryocyte for bone marrow
      mononuclear cells is 3.0 umol/L. Compared with group A, both megakaryocyte colony
      forming units (CFU) and expression rate of CD41a+ cells in group B were
      statistically significantly higher (P < 0.05). As compared with group A, the
      megakaryocyte colony-forming units in group C decreased with statistically
      significant difference, while compared with group C, the megakaryocyte colony
      forming units in group D obviously increased with statistically significant
      difference. CONCLUSIONS: Decitabine is able to induce bone marrow mononuclear
      cells of steroid-resistant ITP patients to differentiate into megakaryocyte and
      the optimal concentration is 3.0 umol/L; ITP plasma is able to inhibit the
      megakaryocyte growth of steroid-resistant ITP patients.

PMID- 26314453
TI  - [Efficacy of Nonmyeloablative Allogeneic Hematopoietic Stem Cells for 14 Case of
      Severe Acquired Aplastic Anemia].
AB  - OBJECTIVE: To investigate the therapeutic efficacy of nonmyeloablative allogeneic
      hematopoietic stem cells transplantation for severe acquired aplastic anemia
      (SAA). METHODS: Fourteen patients with severe acquired aplastic anemia received
      nonmyeloablative allogeneic hematopoietic stem cells transplantation from HLA
      matched sibling donors, among them 8 cases were dagnosed as SAA-I, 6 cases were
      diagnosed as SAA-II. The conditioning regimen consisted of fludarabine (FIUD),
      cyclophosphamide (CTX) and anti-thymocyte globulin (ATG/ALG). The prophylaxis for
      graft-versus-host disease (GVHD) was performed with cyclosporine (CsA) combined
      with mycophenolate mofetil (MMF) or tacrolimus (FK506). RESULTS: All the patients
      gained a quick successfully engraftment of donor hametopoietic cells. The mean
      recovery time for neutrophil and platelet was 9 d and 13 d respectively. All the
      patients have acquired a full donor chimerism before 14 d. There were only 2
      cases of GVHD: one out of them was acute skin GVHD (grade I) at day 70 after
      transplantation and the other was chronic liver GVHD (grade I) in 1 years after
      transplantation, the GVHD more than degree II did not coccur in all patients, 9
      patients with bacterial and fungal mixed infection and (or) virus infection were
      observed, and improved after anti-infection therapy. The median follow-up time
      were 54.5 months (ranged between 5-144 months), and 12 patients remain disease
      free survival currently, only 2 patients died of fungal infectin. CONCLUSION:
      Transplantation of nonmyeloablative allogeneic hematopoietic stem cell is safe
      and effective for the treatment of severe acquired aplastic, but the prevention,
      treatment and monitoring of infection need to be enhance.

PMID- 26314454
TI  - [Efficacy Analysis of Allogeneic Hematopoietic Stem Cell Transplantation for
      Children with Severe Aplastic Anemia].
AB  - OBJECTIVE: To study the efficacy of allogeneic hematopoietic stem cell
      transplantation (allo-HSCT) in children with severe aplastic anemia (SAA).
      METHODS: A total of 11 children with SAA were treated with HLA matched siblings
      (n = 7), umbilical cord blood (n = 2) and haploidentical HSCT (n = 2). RESULTS:
      Among 11 children patients, 10 patients achieved engraftment, but 3 children
      patients experienced secondary graft failure, after donor lymphocyte infusions
      (DLI), they achieved engraftment again. One patient received cord blood
      transplantation and experienced primary graft rejection, but acquired autologous
      recovery. The median time for neutrophils to reach over 0.5 * 10(9)/L was 14 days
      (10-19 days) in the 9 children received bone marrow or bone marrow and peripheral
      blood allo-HSCT, while the median time for platelets to reach over 20 * 10(9)/L
      was 17 days (8-42 days). For the patient received double cord blood
      transplantation, the time of neutrophile and platelet level recovery was 16 days
      and 41 days, respectively. CONCLUSION: If HLA-matched sibling donor is available,
      allo-HSCT can be recommended as the first line of treatment for children with
      SAA. It is feasible for children with SAA to receive allo-HSCT from selective
      donor, including cord blood and haploidentical HSCT. Donor lymphocyte infusions
      can improve engraftment.

PMID- 26314455
TI  - [Diagnostic Value and Clinical Significance of G6PD Activity for the
      Mediterranean Anemia].
AB  - OBJECTIVE: To investigate the diagnostic value and clinical significance of the
      glucose 6-phosphate dehy-drogenase (G6PD) activity for mediterranean anemia (MA),
      so as to provide the reference for early clinical diagnosis and treatment of MA.
      METHODS: The peripheral blood was collected from 100 healthy persons and 168
      patients with MA, then the agarose gel electrophoresis, MA gene detection, blood
      routine examination, serum ferrium levels and G6PD activity assay were performed,
      and the results of evaluating MA were comparatively analyzed. RESULTS: The G6PD
      activity in all type MA patients was obviously higher than that in healthy
      controls (P < 0.01), the MCV value in all type MA patients was significantly
      lower than that in healthy controls (P < 0.01). The detection of G6PD activity
      showed that the sensitivity, specificity, positive and negative likelihood ratio,
      diagnostic index and Youden index of G6PD for MA patients were 85.12%, 68%, 2.66,
      0.219, 1.53 and 0.53 respectively, which suggest the better efficacy of G6PD
      value for diagnosis of MA. CONCLUSION: The G6PDS activity of patients with MA in
      different subtypes is higher than that of healthy persons, the G6PD level has a
      certain diagnostic value for MA, but there is an optimal range.

PMID- 26314456
TI  - [Pooled Umbilical Cord Blood Plasma for Culturing UCMSC and Ex Vivo Expanding
      Umbilical Cord Blood CD34+ Cells].
AB  - OBJECTIVE: To investigate the feasibility of umbilical cord blood plasma (UCP) as
      a replacement for fetal bovine serum (FBS) for culturing mesenchymal stem cells
      (MSC) derived from umbilical cord, and to observe the supporting effects of these
      cells (served as a feeder layer) on ex vivo expanding of human umbilical cord
      blood CD34(+) cells. METHODS: Umbilical cord blood (UCB) units were suitable if
      the Guangzhou cord blood bank donor selection criteria strictly were fulfilled.
      UCP were ready to use after the collection from the plasma depletion/reduction
      during the processing and pooling of suitable UCB units (at least 30 units were
      screened for pathogens and microorganisms, and qualified). Umbilical cord
      mesenchymal stem cells (UCMSC) were harvested from the umbilical cord tissue of
      health full-term newborns after delivery by enzyme digestion and divided into 3
      groups: group 1 and 2 were cultured in the presence of DMEM/F12 containing either
      FBS or UCP; and group 3 was cultured in serum-free medium (StemPro(r) MSC SFM
      CTSTM). Morphology, proliferation and surface marker expression were examined by
      flow cytometry, and the differentiation toward adipogenic and osteogenic lineages
      was used for investigating the effect of media on UCMSC after 3-5 passages. Next,
      the cells cultured in the three different media were cryopreserved and thawed,
      then prepared as feeder layers with the name of UCMSC(FBS), UCMSC(UCP), and
      UCMSC(SFM), respectively. The CD34+ cells were separated from UCB by magnetic
      activated cell sorting (MACS) and divided into 4 groups cultured in StemPro(-34)
      SFM medium added with hematopoietic cytokine combination (StemSpan(r) CC100). The
      control group included only CD34+ cells as group A (blank control) and
      experimental groups included UCMSC(FBS) + CD34+ cells as group B, UCMSC(UCP) +
      CD34+ cells as group C, UCMSC(SFM) + CD34+ cells as group D, and cells in all
      groups were cultured ex vivo for 7 days. The nucleated cell (NC) number was
      counted by cell counter, CD34+ cells were measured by flow cytometry, and
      clonogenic assay was conducted at day 0 and 7 of culture. The expansion
      efficiency was assessed. RESULTS: The morphology (spindle-shaped and plastic
      adherent), the immunophenotype (high positive percentage of CD73, CD90, CD105 and
      CD166) and the differentiation potential (osteogenic and adipogenic) were almost
      indistinguishable among the cells cultured in any of these three media except for
      the expression of CD105 in group 3 (serum-free medium) was lower than that in
      other 2 groups (P < 0.05). UCMSC grown in UCP medium demonstrated significantly
      higher proliferation rates than that in media containing FBS or commercial serum
      free supplement (P < 0.05). After co-culture for 7 days, the CD34+ cell
      percentage decreased in all the groups, while NC were amplified effectively and
      the CD34+ cell number increased with the same order as group C or D group B or A
      (control group) (P < 0.05). As compared with the colony-forming unit (CFU) number
      at day 0, there was no significant difference in the expansion multiple between
      group C and D, while the expansion of CFU in group C were higher than that in
      group B and A. CONCLUSION: The UCP can be used as a better animal-free serum
      supplement for growth, maintenance and differentiation of UCMSC, thus would be a
      safe choice for clinical-scale production of human MSC.

PMID- 26314457
TI  - [Comparison of Biological Characteristics between Human Amnion Epithelial Cells
      and Human Amnion Mesenchymal Stem Cells].
AB  - OBJECTIVE: To compare the biological characteristics between the human amnion
      epithelial cells (hAECs) and human amnion mesenchymal stem cells (hAMSCs).
      METHODS: Human amnion tissues were peeled off from human full term placenta from
      the women with normal healthy singleton pregnancies undergoing elective cesarean
      section. Using low speed-trypsin collagenase digestion method, hAECs and hAMSCs
      were isolated from human amnion tissue. The proliferation and biological
      characteristics of both cells were analyzed and compared by immunofluorescence
      assay, flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR),
      induced differentiation and so on. RESULTS: hAECs were round or oval, and formed
      a confluent monolayer of cobblestone-shaped epithelial cells. hAECs continue to
      proliferate less than 5 passages, while the hAMSCs were fibroblastic and spindle
      shaped, which could continue to proliferate about 30 passages. hAECs expressed
      CK19 and a few of them expressed vimentin; hAMSCs expressed vimentin and did not
      express CK19. Both hAECs and hAMSCs were positive for suface markers CD29, CD73,
      CD44, CD90, OCT-4, Nanog and so on, but hAECs were negative for CD105. Both hAECs
      and hAMSCs were positive for oil red O and akane red staining. CONCLUSIONS: hAECs
      and hAMSCs display stem cell properties. hAECs can not proliferate unlimitly, and
      the proliferation and differentiation ability of hAECs is lower than hAMSCs.

PMID- 26314458
TI  - [Role of Mesenchymal Stem Cells in Preventing GVHD: A Meta-Analysis].
AB  - OBJECTIVE: To evaluate the efficacy of mesenchymal stem cells (MSC) in the
      prevention of graft versus host disease (GVHD) after hematopoietic stem cell
      transplantation (HSCT). METHODS: Randomized controlled trials (RCT) were
      identified from PubMed (1950.1-2014.3), EMbase (1970.1-2014.3), Cochrane Central
      Register of Controlled Trials (CENTRAL, issue 4, 2014) of the Cochrane Library,
      China Biological Medicine (CBM, 1978.1-2014.3). References of retrieved articles
      were also identified. The quality of each RCT was evaluated by the Cochrane
      collaboration's tool for assessing the risk of bias. Data analysis was performed
      with Review Manager 5.1 to evaluate the efficacy of MSC in the prevention of GVHD
      after HSCT. RESULTS: A total of 3 English articles involving 117 patients were
      included. Meta-analysis indicated that MSC did not reduce the incidence of acute
      GVHD and chronic GVHD (RR:0.44, 95% CI: 0.08 to 2.51, P = 0.35; RR:0.85, 95% CI:
      0.54 to 1.33, P = 0.47). However, MSC did not increase occurrence of relapse and
      cytomegalovirus infection (RR:1.52, 95% CI:0.63 to 3.68, P = 0.35;RR:1.05, 95%
      CI:0.72 to 1.53, P = 0.78). Finally, MSC did not improve overall survival rate of
      patients received HSCT (RR:1.06, 95% CI:0.79 to 1.43, P = 0.71). CONCLUSION: MSC
      may have a preventive effect on GVHD in patients undergoing HSCT. However, the
      evidence is weak due to the small sample sizes. Thus, a reliable conclusion about
      the preventive effect of MSC on GVHD at the moment has not been made, further
      larger, high quality, randomized and controlled trials are warranted.

PMID- 26314459
TI  - [Amount Change of Peripheral Blood NK Cells in Patients with Hematologic
      Malignancies and Its Clinical Significance].
AB  - OBJECTIVE: To study the amount change of peripheral blood NK cells in patients
      with hematologic malignancies and its significance. METHODS: A total of 200
      patients with hematologic malignancies in our hospital from June 2013 to March
      2015 were chosen as study objects, out of them 105 patients were in aute stage
      and 95 patients were in remisson stage. At same time 100 people from healthy
      medical examination in our hospital were chosen as control group. The mumber
      change and subgroups of their peripheral blood NK cells were analyzed and
      compared. RESULTS: In control group the absolute number of NK cells was (412.91
      +/- 167.35)/ul, the relative number of NK cells was (13.31 +/- 2.56) %; in group
      at acute stage of leukemia the absolute number of NK cells was (97.84 +/-
      23.18)/ul, the relative number of NK cells was (6.79 +/- 0.78) %; in group at
      acute stage of lymphoma, the absolute number of NK cells was (101.79 +/-
      25.63)/ul, and the relative number of NK cells was (7.12 +/- 1.03) %; in group at
      remission stage of leukemia, the absolute number was (297.17 +/- 87.56)/ul, and
      the relative number was (10.15 +/- 1.64) %; In group at remission of lymphoma,
      the absolute number of NK cells was (288.52 +/- 118.52)/ul, and the relative
      number of NK cells was (10.82 +/- 1.97) %. The number of NK cells between
      different groups showed statistical difference (P < 0.05). In remission group,
      the number of NK cells before and after treatment had statistical difference (P <
      0.05). In control group, the number of CD56(bright) subgroup was (25.28 +/- 4.72)
      %, the number of CD56(bright) subgroup at the acute stage of leukemia was (65.46
      +/- 11.21) %, and the number of CD56(bright) subgroup at the acute stage of
      lymphoma was (70.71 +/- 12.14) %, the number of CD56(bright) subgroup at
      remission stage of leukemia was (23.35 +/- 4.67) %, the number of CD56(bright)
      subgroup at remission stage of lymphoma was (24.89 +/- 4.58) %. The number of
      CD56(bright) subgroup between different groups showed statistical significance (P
      < 0.05). CONCLUSION: The number and function of peripheral blood NK cells in
      patients with hematologic malignancies have been confirmed to be obvious
      decrement, but after treatment the number of NK cells in those patients showed
      increment.

PMID- 26314460
TI  - [Anti-A/B Antibody Titers in Group O Healthy Donors in Hainan Province Area].
AB  - OBJECTIVE: To detect the IgM anti-A (B) and IgG anti-A (B) antibody titers of
      group O healthy donors in Hainan province area, to understand the distribution of
      O-type blood donor IgM and IgG antibody titers and to analyze the relationship
      between antibody titers, so as to provide experimental evidences for the safety
      and feasibility of urgent transfusion of uncrossmatched group O RBCs. METHODS:
      Group O whole blood sample was collected from 80 volunteers blood donors. IgM
      antibody titrations was performed using the immediate spin (IS) tube, and IgG
      antibody titration were performed using the column agglutination technique with
      anti-human globulin (AHG). Using two-way ANOVA, paired t-test and correlation
      analysis, the different types of antibodies were compared. RESULTS: The IgM
      antibody titers distributed in 4-1 024, IgG antibody titer distributed in 2-2
      048. Anti-A antibody titers of IgG were significantly higher than that of IgM
      anti-B, IgG anti-B and IgM anti-A titers (P < 0.05). There was a positive
      correlation bewteen IgM anti-A and anti-B, IgM anti-B and IgG anti-B, IgG anti-A
      and anti-B (P < 0.05). CONCLUSION: Group O blood donors have high antibody titers
      in Hainan province area, type O RBC suspensions should be first screened through
      screening the anti-A titer of IgG, so that can significantly improve the pass
      rate of O-type universal blood and reduce testing costs.

PMID- 26314461
TI  - [Sequence Analysis of A Novel HLA-B*13:68 Allele].
AB  - OBJECTIVE: The purpose of this research was to identify a novel HLA-B allele in
      Chinese population. METHODS: The HLA typing of bone marrow donors was performed
      by PCR-SBT. The ambiguous novel HLA allele was confirmed with GSSP method.
      RESULTS: The sequence of a sample was different from all alleles in the HLA-B
      databases. The sequence analysis showed that it differed from the closet matching
      allele HLA-B*13:01:01 at one nucleotide substitution, 137 T > C in Exon2, which
      resulted in an amino acid change from Phenylalanine (Phe) to Serine (Ser) at
      codon 22. CONCLUSION: A novel allele was identified and named as HLA-B*13:68 by
      the WHO Nomenclature Committee.

PMID- 26314462
TI  - [Identification of B (A) Blood Group and Blood Transfusion for patients with B
      (A) Blood Group].
AB  - OBJECTIVE: To investigate the serological and molecular biological identification
      of B(A) blood group and its reasonable method of blood transfusion for patient
      with B(A) blood group. METHODS: The blood group of patient was detected by
      serological method, at the some time, the genotype of patient was detected by
      using the ABO-TYPE Variant kit and sequence analysis of 6 and 7 exons in ABO
      gene; the washed O red blood cells were used to cross matching blood of
      difficultly matching blood by the three step analysis method. RESULTS: The A weak
      and B strong agglutination were found in positive type, and A1C(3+), BC(-) were
      observed in negative type; the molecular biological identification showed B(A)04,
      640 A > G; the matching blood main side of washed O red blood cells displayed no
      agglutination. CONCLUSION: The identification and analysis of rare blood or
      subtype should be very careful; if necessary, the molecular biological detection
      should carried out; the blood transfusion for patient with rate blood group or
      subtype should be safe, correct and reasonable.

PMID- 26314463
TI  - [Evaluation of Storage Performance of Preserving Bags for Manually Separated
      Platelets].
AB  - OBJECTIVE: To evaluate the storage performance of the domestically made platelet
      storage bags (experimental group) and the United States Trima set platelet
      storage bags (control group). METHODS: The manually separated platelets were
      divided in two equal parts, which was added to control blood bags and
      experimental blood bags respectively, all samples were stored at a 22  degrees C
      +/- 2  degrees C. The platelet count, mean volume, aggregation activity (ADP,
      THR), pH, glucose, lactate concentration, lactate dehydrogenase concentration,
      hypotonic shock reaction, CD62P and phosphatidic acid serine content were
      detected at day 0, 3, 5 and 7 of storage. RESULTS: There was no significant
      difference of platelet quality at day 5 after storage between the experimental
      group and the control group (T-test, P > 0.05). CONCLUSION: Two kinds of platelet
      storage bags have the similar storage performance.

PMID- 26314464
TI  - [Clinical Characteristics and Therapeutic Efficacy Evaluation of 14 Cases of
      Solitary Myeloid Sarcoma].
AB  - OBJECTIVE: To investigate the clinical characteristics, treatment and prognosis
      of solitary myeloid sarcoma (MS). METHODS: The clinical data of 14 solitary MS
      patients were retrospectively analysed, including their clinical features and
      treatment, and were evaluated. RESULTS: A total of 14 cases of solitary MS mainly
      occurred in middle-aged population with the median age 41 years old (17-62 years
      old). The involved sites were more extensive, including breast, testis, spinal
      canal, skin, gastrointestinal system, nose and so on. The poorly differentiated
      cells of small to medium size showed diffuse distribution, relatively consistent
      morphology and a higher ratio of cytoplasm. The nucleus is in round or oval shape
      with fine and dense chromatin. Pathological mitosis was easily observed.
      Expression of MPO, lysozyme, CD43, myeloid-derived cells were positive. Treatment
      methods included surgery, chemotherapy and stem cell transplantation. Median
      survival time of 14 patients was 22.5 months; overall survival (OS) was 35.7%
      (5/14), median disease-free survival reached to 10.4 months on averge (3.5 months
      to 16 months), and 2-year overall survival (OS) was 50.3%. CONCLUSION: The
      incidence of solitary MS is low, with a tendency progressing to leukemia, the
      chemotherapy regimen of anthracycline+cytarabine combined with radiotherapy can
      achieve better clinical efficacy.

PMID- 26314465
TI  - [Pathogenic Genes of A Hereditary Hemorrhagic Telangiectasia Pedigree].
AB  - OBJECTIVE: To identify the mutation of ENG and ALK1 genes in a hereditary
      hemorrhagic telangiectasia pedigree. METHODS: 14 exons of ENG gene and 9 exons of
      ALK1 gene in 11 menbers of this pedigree 4 generation were amplified by reverse
      transcription-polymerase chain reaction (RT-PCR), the PCR products were screened
      by direct sequencing. RESULTS: A nonsense mutation c.447G > A was found in exon 4
      of ENG gen of the pedigreee, resulting in change of Trp 149 into Stop, while no
      gene mutation was found in ALK1 gene. CONCLUSION: The hereditary hemorrhagic
      telangiectasia in this pedigree is caused by the nonsense mutation c.447G > A in
      ENG gene.

PMID- 26314466
TI  - [Morphology Manifestation of Bone Marrow Cells in 155 Newly- Diagnosed Patients
      with POEMS Syndrome].
AB  - OBJECTIVE: To investigate the morphological manifestation of bone marrow cells in
      newly-diagnosed patients with POEMS syndrome. METHODS: The bone marrow cells in
      155 patients with POEMS syndrome were classified and counted by OLYMPUS BX51
      microscope, and the abnormal morphology of bone marrow cells was observed.
      RESULTS: The count of plasma cells with normal morphology was 83.9% (130/155),
      the count of plasma cells with abnormal morphology (< 5 percent) was 12.3%
      (19/155), the count of plasma cells with obvious abnormal morphology (> 10
      percent) was 3.8% (6/155) in patients with POEMS syndrome. CONCLUSION: The
      morphology of plasma cells in the most patients with the POEMS syndrome are
      normal, the minor patients of the POEMS syndrome have little abnormal plasma cell
      morphology, the extremely few patients showed obvious morphological abnormality
      in the bone marrow plasma cells. The higher proportion of plasma cells, the more
      easily and more abnormal plasma cells will be found.

PMID- 26314467
TI  - [In vivo Cell CFSE Fluorescence Negative Staining for Detection of Super
      Paramagnetic Iron Oxide Nanoparticles Phagocytosed by Mouse Mononuclear
      Macrophage Leukemia Cells-RAW264.7].
AB  - OBJECTIVE: To explore the feasibility and fluorescence characteristics of CFSE
      negative staining for in vivo cell imaging of super paramagnetic iron oxide
      nanoparticles (SPIO) phagocytosed by mouse mononuclear macrophage leukemia cells
      RAW264.7. METHODS: After labeled with SPIO, the RAW264.7 macrophages were stained
      with Prussian blue stain and CFSE fluorescence negative stain step by step.
      Furthermore, trypan blue staining was used to evaluate cell viability of cells
      which stained with CFSE. At last, laser scanning confocal microscope was used to
      measure SPIO in cells through CFSE fluorescence negative stain method. RESULTS:
      SPIO within RAW264.7 macrophages showed blue in Prussian's blue staining, while
      showed negative area in CFSE negative staining. Good consistencies between
      Prussian's blue staining and CFSE negative staining were observed. In addition,
      RAW264.7 macrophages showed high viability after SPIO/CFSE dual-labeled method,
      proved by typan stain. CONCLUSION: The CFSE fluorescence negative staining may be
      used for detecting SPIO that phagocytosed by RAW264.7 macrophages and it is
      showed good consistency that confirmed one another when compared to classic
      Prussian' blue staining.

PMID- 26314468
TI  - [Expression of MicroRNA-148/152 Family in the Hematological Malignancies].
AB  - MicroRNAs (miRNAs) are small noncoding RNA molecules containing 18-22 nucleotides
      that regulate gene expression through imperfect interactions with sequences in
      the 3'-untranslated region (3'-UTR) of target genes. Members of the microRNA
      148/152 (miR-148/152) family, which include microRNA-148a (miR-148a), microRNA
      148b (miR-148b) and microRNA-152 (miR-152), are of great importance in the
      development of some tumor diseases. Several studies have demonstrated that
      members of the miR-148/152 family were expressed differently in many kinds of
      malignancies, and they play a variety of biological functions, such as regulating
      tumor growth, proliferation, apoptosis, angiogenesis, and sensitivity to drugs
      through regulating the expression of target genes. The miR-148/152 family is
      regulated by methylation of their CPG islands, which reduce the expression of miR
      148/152 family members. Interaction has been observed between DNA methylation and
      miR-148/152 family members through their target gene: DNMT1/3b, an important gene
      for DNA methylation. So expressions of DNMT1/3b are inversely restricted to the
      expression level of miR-148a/152. This might result in overexpression of
      DNMT1/3b, promoting DNA methylation. And then, more DNMT1/3b can be expressed. A
      novel miR-148a/152-DNMT1/3b regulatory circuit might exist in tumors. Epigenetic
      abnormalities, especially high methylation of promoter play an important role in
      occurrence and development of hematological malignancies. Demethylation treatment
      has become another important way for the treatment. This article summarizes the
      expression of miR-148/152 family in hematological malignancies, aiming at
      expounding the signicance of relationship between DNA methylation modification
      and microRNA. 

PMID- 26314469
TI  - [Exosomes Derived from Mesenchymal Stem Cells--the Future Ideal Vector of
      Biological Therapy].
AB  - MSC-exosomes are homogeneous menbrane vesicles with diameter 40-100 nm, derived
      from mesenchymal stem cells at physiological or pathology conditions. MSC
      exosomes contain a great quantity and a wide variety of bioactive substances,
      such as proteins and miRNA. MSC-exosomes transfer bioactive substances to
      recipient cells to affect their functions through membrane fusion or endocytosis,
      which like the storage pools of signal vehicles for cell-to-cell comunication in
      vivo. MSC-exosomes can mimic the beneficial effect of MSC treatment, such as the
      promotion of tissue repair or the immune regulation. The biological property and
      functions of MSC-exosomes are reviwed in this article. 

PMID- 26314470
TI  - [Advances of Researches on the Role of Histone Modification in Hematological
      Neoplasms].
AB  - As a crucial part of epigenetic regulation, the histone modification catalyzed by
      histone modification enzymes can alter the chromatin structure and modulate the
      gene expression. The role of histone modification in disease pathogenesis,
      especially in tumorigenesis, has become a research hotspot. The deregulation of
      histone modification, such as the overexpression and gain-of-function mutations
      of histone methyltransferase EZH2, the inactive mutations of histone
      methyltransferase MLL2, histone acetyltransferase CREBBP and EP300 are crucial
      for the development of hematological neoplasms. Some of Epi-drugs such as HDAC
      inhibitors, EZH2 inhibitors, are already clinically used, some are still in basic
      research stage, which are important field of new drug development for
      hematological neoplasms. In this review, the researches advances of basic medical
      sciences and clinical applications of aberrant histone modifications in
      hematological neoplasms are summarized. 

PMID- 26314471
TI  - [Research Progress on DKK1 Gene in Leukemia].
AB  - A number of studies have demonstrated that the methylation of Dickkopf-1 (DKK1)
      gene promoter is related with the occurrence and development of many neoplastic
      diseases. By means of binding with corresponding receptors, DKK1 blocks the
      transduction pathway of Wnt/beta-catenin/TCF and inhibits the proliferation and
      invasion of tumor cells, inducing apoptosis. Leukemia is a hyperplastic disease
      of hematopoietic stem cell malignant clone. Its pathogenesis has been confirmed
      to be closely related with the aberrant activation of Wnt signaling pathway. This
      pathway is associated with the self-renewal and proliferation of the
      hematopoietic stem cells, which can regulate growth, differentiation, migration
      of the cells, angiogenesis and embryonic development. Its expression is regulated
      by some suppressor genes like Dickkopf 1 (DKK1). Leukemia often accompanied by
      methylation modification of the DKK1 gene, so as to leads to silencing itself and
      activation of the Wnt signaling pathway, which cause the occurrence of leukemia.
      Some therapeutic methods on leukemia aiming at DKK1 gene have been reported,
      among which DKK1 gene was demethylated. The intensive study on the expression and
      function of DKK1 should be important for the early diagnosis, treatment and
      prognosis. This article reviews the current progress in this field. 

PMID- 26314472
TI  - [Effect of Ikaros in B Cell Acute Lymphoblastic Leukemia].
AB  - The Ikaros - a DNA-binding zinc finger protein, acting as a regulator of
      chromatin remodeling and gene transcription, is crucial for regulating the
      development and function of the immune system and acting as a master regulator of
      hematopoietic differentiation. Function-loss mutations of IKZF1, gene encoding
      Ikaros are frequent in B cell acute lymphoblastic leukemia (B-ALL) and are
      associated with a poor prognosis. This review briefly summarizes the available
      data regarding the structure and function of Ikaros, the role of Ikaros as a
      tumor suppressor in B-ALL, and its regulation mechanism. 

PMID- 26314473
TI  - [Genomic Instability in Acute Transformation of Chronic Myelogenous Leukemia].
AB  - Chronic myeloid leukemia (CML) is a myeloproliferative disorder, characterized by
      excessive proliferation of myeloid cells. CML patients in early phase [also known
      as chronic phase (CP)] usually respond to treatment with tyrosine kinase
      inhibitors (TKI), some patients respond initially to TKI, but later become
      resistant, then resulting in the transformation from CP to more advanced phase,
      which were subclassified as either accelerated phase or blastic phase. At
      present, the molecular mechanisms of CML have been not yet clear, and acute
      transformation has been not fully understood, studies have shown that genomic
      instability promotes the acute conversion of CML. This review discusses the
      molecular mechanisms leading to the transformation of CML, and some therapeutic
      approaches. 

PMID- 26314474
TI  - [Advances on Extrocorporeal Photochemotherapy in the Treatment of Chronic Graft
      Versus-Host Disease].
AB  - Chronic graft-versus-host disease (cGVHD) is a common complication after
      allogeneic hematopoietic stem cell transplantation (allo-HSCT), which is also one
      of the major causes of patients' death following transplantation. Recently,
      extracorporeal photochemotherapy (ECP) has shown a considerable efficacy in cGVHD
      treatment, which is based on the infusion of autologous peripheral blood
      mononuclear cells collected by aphesis, incubated with the photoactivable drug 8
      methoxypsoralen (8-MOP) and UV-A irradiation. The therapeutic effect of ECP is
      mainly achieved by the induction of cell apoptosis, influencing the function of
      dendritic cells and the induction of immune tolerance. ECP has many advantages in
      the treatment of cGVHD, such as no increasing the risk of infection in patients,
      unaffecting the graft-versus-leukemia effect, nearly no side effect and so on.
      Many medical centers have done a lot of research on the treatment of cGVHD in
      both children and adults by using ECP and achieved good results. CD19(+) CD21(-)
      B lymphocytes, serum BAFF and serum TNFalpha can be used to measure and early
      evaluate the efficacy of ECP treatment. The effect of ECP is associated with many
      factors, and certain complications may occur during the treatment. At present,
      the application of ECP treatment is limited by the unclear mechanisms, varying
      treatment cycles in different studies, and small number of patients in clinical
      research. In the near future, with deeper basic research, increasing the case
      number and standard clinical treatment, ECP will have a more extensive
      application prospects. This review focuses mainly on the clinical advances of ECP
      in the treatment of cGVHD. 

PMID- 26314475
TI  - [Research Progress on Cytometric Bead Assay for Platelet Antibody Detection].
AB  - Anti-platelet specific antibody is one of the most important reasons leading to
      thrombocytopenia and megakaryocyte dysmaturity. The detection of platelet
      autoantibodies is an important step in the diagnosis of ITP because of the
      absence of specific clinic feature. The monoclonal antibody-specific
      immobilization of platelet antigens (MAIPA) has become a "gold standard" for
      determination of PLT specific antibody, which has high specificity and low
      sensitivity. However, this assay is time-consuming and tedious work. Routine use
      of this assay in hospital is difficult. Recently, some researches reporded the
      cytometric bead assay that has higher sensitivity than MAIPA, and so probably
      solves the problem of time-consuming partly, that also can use different beads
      for simultaneous detection. This review focuses on recent progress of the
      cytometric bead assay. 

PMID- 26314476
TI  - [Treatment Progress of Immune Thrombocytopenia].
AB  - Immune thrombocytopenia (ITP) is caused by platelet autoantibodies and T-cell
      dysregulation. Both platelets and their precursor megakaryocytes may be targeted
      leading to platelet destruction and insufficient production. Current treatments
      for ITP, including corticosteroids, rituximab, splenectomy and TPO receptor
      agonists can not reverse the disease process and can be limited by their side
      effects including infection and thrombosis. New methods, such as anti-CD154
      antibody, FcgammaRIIb and Syk (spleen tyrosine kinase) inhibitor, can target at
      certain key steps in the disease process, showing the potential to limite
      systemic side effects and to decrease the morbidity and mortality of ITP
      patients. In this article, the recent therapeutic strategies, the new types of
      drugs and the further study orientation (or the way of further studies) are
      reviewed. 

PMID- 26314477
TI  - [Research Progress on Pathogenesis of Aplastic Anemia].
AB  - Aplastic anemia is a disease characterized by low bone marrow hematopoietic
      function and derease of whole blood cells caused by a variety of reasons. Its
      pathogenesis includes abnormality of hematopoietic stem cells (seed theory),
      hematopoietic microenvironment (soil theory) and immune function (such as worms
      theory). These 3 causes of disease interact each other and facilitate the
      development of aplastic anemia, thereby increase the complexity of the
      etiological diagnosis and uncertainty of treatment. On this basis, this review
      summarizes the latest research progress on the blood supply of bone marrow
      microcirculation in the hematopoietic microenvironment, stromal cells, cytokins,
      the immune function of dendritic cells, natural killer cells, T cell subgroup,
      the secretion of cytokines, cell signal transduction, and hematopoietic stem cell
      gene abnormality to provides the theoretic basis for the diagnosis and treatment
      of aplastic anemia. 

PMID- 26314478
TI  - [Research Progress on TKI Resistance of CML Cells Mediated by MSC through
      CXCL12/CXCR4 Axis].
AB  - Although the tyrosinekinase inhibitors (TKI) displayed a significant curative
      effect on chronic myeloid leukemia (CML), but the drug resistance in treatment
      course of this disease still can not be avoided. Studies recently have shown that
      the mesenchymal stem cells (MSC) can induce CML cells to resist TKI therapy by
      CXCL12/CXCR4 axis from multiple aspects, such as the directional migration of CML
      cells, adherence to marrow cavity, the mediation of cell protective dormancy,
      activations of numerous survival signaling pathways, the suppression of
      mitochondrial-dependent apoptosis and the up-regulated expression of BCL-6. The
      combination of TKI and CXCR4 antagonists will be a novel treatment strategy to
      raise the genetic cure rate of CML. In this article, the pathways of drug
      resistance, pathways of sensitivity to CXCL12 and pathways of CML cell adherence
      to marrow cavity in CML cells mediated by MSC were reviewed. 

PMID- 26314479
TI  - Magnetic resonance elastography for staging liver fibrosis in non-alcoholic fatty
      liver disease: a diagnostic accuracy systematic review and individual participant
      data pooled analysis.
AB  - OBJECTIVES: We conducted an individual participant data (IPD) pooled analysis on
      diagnostic accuracy of MRE to detect fibrosis stage in patients with non
      alcoholic fatty liver disease (NAFLD). METHODS: Through a systematic literature
      search, we identified studies of MRE (at 60-62.5 Hz) for staging fibrosis in
      patients with NAFLD, using liver biopsy as gold standard, and contacted study
      authors for IPD. Through pooled analysis, we calculated the cluster-adjusted
      AUROC, sensitivity and specificity of MRE for any (>=stage 1), significant
      (>=stage 2) and advanced (>=stage 3) fibrosis and cirrhosis (stage 4). RESULTS:
      We included nine studies with 232 patients with NAFLD (mean age, 51 +/- 13 years;
      37.5% males; mean BMI, 33.5 +/- 6.7 kg/m(2); interval between MRE and biopsy <1
      year, 98.3%). Fibrosis stage distribution (stage 0/1/2/3/4) was 33.6, 32.3, 10.8,
      12.9 and 10.4%, respectively. Mean AUROC (and 95% CIs) for diagnosis of any,
      significant or advanced fibrosis and cirrhosis was 0.86 (0.82-0.90), 0.87 (0.82
      0.93), 0.90 (0.84-0.94) and 0.91 (0.76-0.95), respectively. Similar diagnostic
      performance was observed in stratified analysis based on sex, obesity and degree
      of inflammation. CONCLUSIONS: MRE has high diagnostic accuracy for detection of
      fibrosis in NAFLD, independent of BMI and degree of inflammation. KEY POINTS: *
      MRE has high diagnostic accuracy for detection of fibrosis in NAFLD. * BMI does
      not significantly affect accuracy of MRE in NAFLD. * Inflammation had no
      significant influence on MRE performance in NAFLD for fibrosis.

PMID- 26314481
TI  - Brain herniations into the dural venous sinus or calvarium: MRI findings,
      possible causes and clinical significance.
AB  - OBJECTIVES: To determine frequency, imaging features and clinical significance of
      herniations of brain parenchyma into dural venous sinuses (DVS) and/or calvarium
      found on MRI. METHODS: A total of 6160 brain MRI examinations containing at least
      one high-resolution T1- or T2-weighted sequence were retrospectively evaluated to
      determine the presence of incidental brain herniations into the DVS or calvarium.
      MRI sequences available for review were evaluated according to their capability
      to demonstrate these herniations. Patients' symptoms and clinical findings were
      recorded. RESULTS: Twenty-one (0.32 %) brain parenchyma herniations into the DVS
      (n = 18) or calvarium (n = 3) in 20 patients were detected. The most common
      locations of the herniations were the transverse sinuses (n = 13) and those
      involving inferior gyrus of the temporal lobe (n = 9). High-resolution T1- and T2
      weighted sequences were equally useful in the detection of these brain
      herniations. According to clinical symptoms, brain herniations were considered to
      be incidental but headaches were present in nine patients. CONCLUSION: Brain
      herniations with surrounding cerebrospinal fluid (CSF) into the DVS and/or
      calvarium are incidental findings and not proven to be associated with any
      symptoms. Although rare, these herniations are more common than previously
      recognized and should not be confused with arachnoid granulations, clots or
      tumours. KEY POINTS: * Brain herniations into the DVS are more common than
      previously assumed. * The most frequent locations are the transverse sinus. *
      These herniations are incidental findings. * The relationship between brain
      herniation into DVS and headache is uncertain. * High-resolution MR sequences are
      most useful in detection of brain herniations.

PMID- 26314480
TI  - Neoadjuvant radiation in primary extremity liposarcoma: correlation of MRI
      features with histopathology.
AB  - OBJECTIVE: To evaluate MRI features of response of primary extremity liposarcoma
      (LPS) to neoadjuvant radiation therapy (RT) with histopathologic correlation.
      METHODS: In this IRB-approved study including 125 patients with extremity LPS
      treated with neoadjuvant RT from 2000 to 2013, MRI of the primary tumour in 18
      patients (5 pleomorphic LPS, 13 myxoid LPS) before and after RT were reviewed by
      two radiologists by consensus. Histopathology of the surgical specimens was
      reviewed by a pathologist with expertise in sarcomas. RESULTS: In the pleomorphic
      LPS cohort, 3/5 tumours increased in size; 3/5 decreased in enhancing component;
      and 3/5 increased in peritumoral oedema, intratumoral haemorrhage, and necrosis.
      In the myxoid LPS cohort, 12/13 tumours decreased in size, 8/13 decreased in
      enhancing component, and 5/13 increased in internal fat following RT.
      Histopathology showed >=50% residual tumour in 1/5 pleomorphic LPS and 2/13
      myxoid LPS. Hyalinization/necrosis of >=75% was noted in 4/5 pleomorphic LPS and
      11/13 myxoid LPS. Cytodifferentiation was noted in 1/5 pleomorphic and 9/13
      myxoid LPS. CONCLUSION: While pleomorphic LPS showed an increase in size,
      peritumoral oedema, intratumoral haemorrhage, and necrosis on MRI following
      neoadjuvant RT, myxoid LPS showed a decrease in size and enhancement with an
      increase in internal fat. KEY POINTS: * Pleomorphic LPS commonly increase in size
      and necrosis on MRI following RT. * Myxoid LPS commonly decrease in size and
      enhancement on MRI following RT. * Myxoid LPS often increase in fatty component
      on MRI following RT.

PMID- 26314482
TI  - 7 Tesla quantitative hip MRI: T1, T2 and T2* mapping of hip cartilage in healthy
      volunteers.
AB  - OBJECTIVES: To evaluate the technical feasibility and applicability of
      quantitative MR techniques (delayed gadolinium-enhanced MRI of cartilage
      (dGEMRIC), T2 mapping, T2* mapping) at 7 T MRI for assessing hip cartilage.
      METHODS: Hips of 11 healthy volunteers were examined at 7 T MRI with an 8-channel
      radiofrequency transmit/receive body coil using multi-echo sequences for T2 and
      T2* mapping and a dual flip angle gradient-echo sequence before (T10) and after
      intravenous contrast agent administration (T1Gd; 0.2 mmol/kg Gd-DTPA(2-) followed
      by 0.5 h of walking and 0.5 h of rest) for dGEMRIC. Relaxation times of cartilage
      were measured manually in 10 regions of interest. Pearson's correlations between
      R1delta = 1/T1Gd - 1/T10 and T1Gd and between T2 and T2* were calculated. Image
      quality and the delineation of acetabular and femoral cartilage in the relaxation
      time maps were evaluated using discrete rating scales. RESULTS: High correlations
      were found between R1delta and T1Gd and between T2 and T2* relaxation times (all
      p < 0.01). All techniques delivered diagnostic image quality, with best
      delineation of femoral and acetabular cartilage in the T2* maps (mean 3.2 out of
      a maximum of 4 points). CONCLUSIONS: T1, T2 and T2* mapping of hip cartilage with
      diagnostic image quality is feasible at 7 T. To perform dGEMRIC at 7 T, pre
      contrast T1 mapping can be omitted. KEY POINTS: * dGEMRIC of hip cartilage with
      diagnostic image quality is feasible at 7 T. * To perform dGEMRIC at 7 T, pre
      contrast T1 mapping can be omitted. * T2(*) mapping of hip cartilage with
      diagnostic image quality is feasible at 7 T. * T2 and T2* relaxation times of
      cartilage were highly correlated at 7 T. * Best delineation of femoral and
      acetabular cartilage was found in T2* maps.

PMID- 26314483
TI  - Tip-enhanced Raman spectroscopy: tip-related issues.
AB  - After over 15 years of development, tip-enhanced Raman spectroscopy (TERS) is now
      facing a very important stage in its history. TERS offers high detection
      sensitivity down to single molecules and a high spatial resolution down to sub
      nanometers, which make it an unprecedented nanoscale analytical technique
      offering molecular fingerprint information. The tip is the core element in TERS,
      as it is the only source through which to support the enhancement effect and
      provide the high spatial resolution. However, TERS suffers and will continue to
      suffer from the limited availability of TERS tips with a high enhancement, good
      stability, and high reproducibility. This review focuses on the tip-related
      issues in TERS. We first discuss the parameters that influence the enhancement
      and spatial resolution of TERS and the possibility to optimize the performance of
      a TERS system via an in-depth understanding of the enhancement mechanism. We then
      analyze the methods that have been developed for producing TERS tips, including
      vacuum-based deposition, electrochemical etching, electrodeposition, electroless
      deposition, and microfabrication, with discussion on the advantages and
      weaknesses of some important methods. We also tackle the issue of lifetime and
      protection protocols of TERS tips which are very important for the stability of a
      tip. Last, some fundamental problems and challenges are proposed, which should be
      addressed before this promising nanoscale characterization tool can exert its
      full potential. Graphical Abstract ?. 

PMID- 26314484
TI  - Aggregation behavior of fullerenes in aqueous solutions: a capillary
      electrophoresis and asymmetric flow field-flow fractionation study.
AB  - In this work, the electrophoretic behavior of hydrophobic fullerenes
      [buckminsterfullerene (C60), C70, and N-methyl-fulleropyrrolidine (C60-pyrr)] and
      water-soluble fullerenes [fullerol (C60(OH)24); polyhydroxy small gap fullerene,
      hydrated (C120(OH)30); C60 pyrrolidine tris acid (C60-pyrr tris acid); and (1,2
      methanofullerene C60)-61-carboxylic acid (C60CHCOOH)] in micellar electrokinetic
      capillary chromatography (MECC) was evaluated. The aggregation behavior of the
      water-soluble compounds in MECC at different buffer and sodium dodecyl sulfate
      (SDS) concentrations and pH values of the background electrolyte (BGE) was
      studied by monitoring the changes observed in the electrophoretic pattern of the
      peaks. Broad and distorted peaks that can be attributed to fullerene aggregation
      were obtained in MECC which became narrower and more symmetric by working at low
      buffer and SDS concentrations (below the critical micelle concentration,
      capillary zone electrophoresis (CZE) conditions). For the characterization of the
      suspected aggregates formed (size and shape), asymmetrical flow field-flow
      fractionation (AF4) and transmission electron microscopy (TEM) were used. The
      results showed that the increase in the buffer concentration promoted the
      aggregation of the particles, while the presence of SDS micelles revealed
      multiple peaks corresponding to particles of different aggregation degrees.
      Furthermore, MECC has been applied for the first time for the analysis of C60 in
      two different cosmetic products (i.e., anti-aging serum and facial mask). 

PMID- 26314485
TI  - Vasoactive intestinal peptide represses activation of tumor-associated
      macrophages in gastric cancer via regulation of TNFalpha, IL-6, IL-12 and iNOS.
AB  - Vasoactive intestinal peptide (VIP) has been regarded as deactivator for
      macrophages. However, the depressive effect of VIP on tumor-associated
      macrophages (TAM) has not been recognized. In the present study, we investigated
      the effect of VIP on gastric cancer via TAM by suppressing expression levels of
      TNFalpha, IL-6, IL-12 and iNOS. Real-time PCR was carried out to examine the
      expression of CD68 to determine the levels of TAM. The effect of VIP on cell
      activities was assayed by proliferation assay, colony formation and flow
      cytometry analysis. The co-culture of TAM and human gastric cancer cell line MKN
      45 were performed to understand whether the VIP affects the gastric cancer cells
      via TAM. Further, the tumor formation in a nude mouse model and VIP injection
      were performed to illustrate the effect on tumor progression in vivo. CD68 was
      high expressed in gastric cancer indicating high level of TAM in gastric cancer.
      Treatment with VIP significantly depressed TAM activation. Moreover, the
      expression of TNFalpha, IL-6, IL-12 and iNOS in TAM were depressed by VIP
      treatment, and the VIP treated TAM depressed gastric cancer cells. The experiment
      in the nude mouse model also suggested that by injection with TAM+VIP, the tumor
      volume and tumor weight were both decreased significantly. These data suggest
      that treatment with VIP inhibits gastric cancer.

PMID- 26314486
TI  - The spontaneous formation of single-molecule junctions via terminal alkynes.
AB  - Herein, we report the spontaneous formation of single-molecule junctions via
      terminal alkyne contact groups. Self-assembled monolayers that form spontaneously
      from diluted solutions of 1, 4-diethynylbenzene (DEB) were used to build single
      molecule contacts and assessed using the scanning tunneling microscopy-break
      junction technique (STM-BJ). The STM-BJ technique in both its dynamic and static
      approaches was used to characterize the lifetime (stability) and the conductivity
      of a single-DEB wire. It is demonstrated that single-molecule junctions form
      spontaneously with terminal alkynes and require no electrochemical control or
      chemical deprotonation. The alkyne anchoring group was compared against typical
      contact groups exploited in single-molecule studies, i.e. amine (benzenediamine)
      and thiol (benzendithiol) contact groups. The alkyne contact showed a conductance
      magnitude comparable to that observed with amine and thiol groups. The lifetime
      of the junctions formed from alkynes were only slightly less than that of thiols
      and greater than that observed for amines. These findings are important as (a)
      they extend the repertoire of chemical contacts used in single-molecule
      measurements to 1-alkynes, which are synthetically accessible and stable and (b)
      alkynes have a remarkable affinity toward silicon surfaces, hence opening the
      door for the study of single-molecule transport on a semiconducting electronic
      platform. 

PMID- 26314487
TI  - Floods in Myanmar damage hundreds of health facilities.

PMID- 26314488
TI  - Iraq's health services curtailed by funding shortfall.

PMID- 26314489
TI  - Postural modification to the standard Valsalva manoeuvre for emergency treatment
      of supraventricular tachycardias (REVERT): a randomised controlled trial.
AB  - BACKGROUND: The Valsalva manoeuvre is an internationally recommended treatment
      for supraventricular tachycardia, but cardioversion is rare in practice (5-20%),
      necessitating the use of other treatments including adenosine, which patients
      often find unpleasant. We assessed whether a postural modification to the
      Valsalva manoeuvre could improve its effectiveness. METHODS: We did a randomised
      controlled, parallel-group trial at emergency departments in England. We randomly
      allocated adults presenting with supraventricular tachycardia (excluding atrial
      fibrillation and flutter) in a 1:1 ratio to undergo a modified Valsalva manoeuvre
      (done semi-recumbent with supine repositioning and passive leg raise immediately
      after the Valsalva strain), or a standard semi-recumbent Valsalva manoeuvre. A 40
      mm Hg pressure, 15 s standardised strain was used in both groups. Randomisation,
      stratified by centre, was done centrally and independently, with allocation with
      serially numbered, opaque, sealed, tamper-evident envelopes. Patients and
      treating clinicians were not masked to allocation. The primary outcome was return
      to sinus rhythm at 1 min after intervention, determined by the treating clinician
      and electrocardiogram and confirmed by an investigator masked to treatment
      allocation. This study is registered with Current Controlled Trials
      (ISRCTN67937027). FINDINGS: We enrolled 433 participants between Jan 11, 2013,
      and Dec 29, 2014. Excluding second attendance by five participants, 214
      participants in each group were included in the intention-to-treat analysis. 37
      (17%) of 214 participants assigned to standard Valsalva manoeuvre achieved sinus
      rhythm compared with 93 (43%) of 214 in the modified Valsalva manoeuvre group
      (adjusted odds ratio 3.7 (95% CI 2.3-5.8; p<0.0001). We recorded no serious
      adverse events. INTERPRETATION: In patients with supraventricular tachycardia, a
      modified Valsalva manoeuvre with leg elevation and supine positioning at the end
      of the strain should be considered as a routine first treatment, and can be
      taught to patients. FUNDING: National Institute for Health Research.

PMID- 26314490
TI  - Iron deficiency anaemia.
AB  - Anaemia affects roughly a third of the world's population; half the cases are due
      to iron deficiency. It is a major and global public health problem that affects
      maternal and child mortality, physical performance, and referral to health-care
      professionals. Children aged 0-5 years, women of childbearing age, and pregnant
      women are particularly at risk. Several chronic diseases are frequently
      associated with iron deficiency anaemia--notably chronic kidney disease, chronic
      heart failure, cancer, and inflammatory bowel disease. Measurement of serum
      ferritin, transferrin saturation, serum soluble transferrin receptors, and the
      serum soluble transferrin receptors-ferritin index are more accurate than classic
      red cell indices in the diagnosis of iron deficiency anaemia. In addition to the
      search for and treatment of the cause of iron deficiency, treatment strategies
      encompass prevention, including food fortification and iron supplementation. Oral
      iron is usually recommended as first-line therapy, but the most recent
      intravenous iron formulations, which have been available for nearly a decade,
      seem to replenish iron stores safely and effectively. Hepcidin has a key role in
      iron homoeostasis and could be a future diagnostic and therapeutic target. In
      this Seminar, we discuss the clinical presentation, epidemiology,
      pathophysiology, diagnosis, and acute management of iron deficiency anaemia, and
      outstanding research questions for treatment.

PMID- 26314491
TI  - Supraventricular tachycardia: back to basics.

PMID- 26314493
TI  - Electrodeposition of Pluronic F127 assisted rod-like EMD/carbon arrays for
      efficient energy storage.
AB  - In the traditional Duracell battery, the results obtained to date remain marginal
      in terms of cyclability. The development of the existing Zn-MnO2 with superior
      electrochemical performance for use in alkaline rechargeable batteries is
      reported. Electrolytic manganese dioxide (EMD) was synthesized from a
      conventional manganese sulphate bath but having a unique non-ionic surfactant
      (Pluronic F127), and activated carbon, in an electrolytic cell. The surface areas
      and morphologies of the as-prepared EMDs were influenced by the presence of these
      novel additives in the solution while the X-ray data revealed that there was no
      noticeable change in the crystal orientations thus all the EMDs were structurally
      similar. The synergistic effect of the optimal ratio of surfactant to carbon
      powder produced rod-like arrays exhibiting a larger surface area, which
      facilitates ion transport for better energy storage. It is interesting to note
      that EMD deposited in the presence of F127 showed better cyclability whereas in
      the presence of carbon, although it showed better storage capability, it was
      endowed with poor efficiency when compared with the surfactant added sample,
      nevertheless the results are better than the existing Zn-MnO2 technology
      (additive free EMD). Therefore, both the surfactant (50 mg dm(-3)) and the
      activated carbon (5 g dm(-3)) have been added together in the bath and the
      resultant EMD exhibits a high specific capacity and an excellent cycling
      stability. Moreover, the presence of surfactant and activated carbon improved the
      discharge capacity and its retention thus making this alkaline technology
      feasible for storing renewable energy for future use. The synergistic effect and
      the mechanism involved have been discussed. 

PMID- 26314492
TI  - Influence of MTHFR C677T polymorphism on methotrexate monotherapy discontinuation
      in rheumatoid arthritis patients: results from the GAPAID European project.
AB  - OBJECTIVES: Methotrexate (MTX) is the most widely prescribed drug for rheumatoid
      arthritis (RA) patients, but 45% of them discontinue therapy within two years,
      either due to inefficacy or toxicity. Several authors have reported contradictory
      results related to C677T polymorphism in the MTHFR gene and response to MTX in
      RA. The purpose of this study was to further explore this genotype-response
      association in a European RA population. METHODS: This retrospective longitudinal
      study included a total of 269 RA patients from Italy and Hungary, of whom 73.2%
      had available data on MTX treatment (197 patients). C677T polymorphism
      (rs1801133) was genotyped by quantitative PCR using TaqMan assays. Genotype
      association analysis and Kaplan-Meier method were used for statistical
      comparisons between patients continuing and patients who abandoned MTX treatment.
      RESULTS: A total of 85 out of the 197 RA patients (43%) abandoned MTX treatment
      by the time of analysis. No significant genotype-MTX discontinuation association
      was found for the overall population, either at the end of the study (p=0.375),
      or during the follow-up (p=0.324). When the analysis was restricted to the 68
      patients on MTX monotherapy, a borderline association (OR 3.15, 95% CI 0.93
      10.67, p=0.057) was noted with the recessive genetic model. In agreement with
      that, a Kaplan-Meier analysis showed a significantly shorter time-to
      discontinuation of MTX monotherapy for homozygous carriers of the T-allele
      (p=0.042). CONCLUSIONS: These results demonstrate that the C677T polymorphism in
      the MTHFR gene is involved in MTX monotherapy discontinuation in a multicentre
      European patient cohort, confirming previous results.

PMID- 26314495
TI  - Site- and state-selected photofragmentation of 2Br-pyrimidine.
AB  - The fragmentation of the 2Br-pyrimidine molecule following direct valence
      photoionization or inner shell excitation has been studied by electron-ion
      coincidence experiments. 2Br-pyrimidine has been chosen as a model for the class
      of pyrimidinic building blocks of three nucleic acids and several
      radiosensitizers. It is known that the site- and state-localization of energy
      deposition, typical of inner shell excitation, results in the enhancement of the
      total ion yield as well as in changes in the relative intensity of the different
      fragmentation channels. Here we address the question of the origin of this
      selective fragmentation by using electron-ion coincidence techniques. The results
      show that the fragmentation is strongly selective in the final singly charged ion
      state, independently of the process that leads to the population of that state,
      and the dominant fragmentation patterns correlate with the nearest appearance
      potential. 

PMID- 26314494
TI  - The inhibitory effects of AR/miR-190a/YB-1 negative feedback loop on prostate
      cancer and underlying mechanism.
AB  - Prostate cancer at advanced stages including metastatic and castration-resistant
      cancer remains incurable due to the lack of effective therapies. MiR-190a belongs
      to the small noncoding RNA family and has an important role in breast cancer
      metastasis. However, it is still unknown whether miR-190a plays a role in
      prostate cancer development. Herein, we first observed AR/miR-190a/YB-1 forms an
      auto-regulatory negative feedback loop in prostate cancer: miR-190a expression
      was down-regulated by AR activation; YB-1 functions are as an AR activator; miR
      190a inhibited AR expression and transactivation through direct binding to 3'UTR
      of YB-1 gene. MiR-190a contributes the human prostate cancer cell growth through
      AR-dependent signaling. Moreover, we examined the expression of miR-190a and
      observed a significant decrease in human prostate cancers. Reduced expression of
      miR-190a was inversely correlated to AR levels of prostate cancer patients, and
      patients with higher miR-190a expression in their tumor have improved tumor-free
      survival. Taken together, our findings identified a biochemical and functional
      link between miR-190a with reduced expression in advanced prostate cancer, YB-1
      and AR signaling in prostate cancer. 

PMID- 26314496
TI  - Age-Related Differences in Muscle Shear Moduli in the Lower Extremity.
AB  - This study investigated the age-related differences in shear moduli of the rectus
      femoris muscle (RF), the lateral head of the gastrocnemius muscle (LG) and the
      soleus muscle (SOL) using shear wave ultrasound elastography. Thirty-one young
      individuals and 49 elderly individuals volunteered for this study. The shear
      modulus of RF was determined at 50% of the thigh length, and those of LG and SOL
      were determined at 30% of the lower leg length. RF and LG shear moduli were
      significantly higher in young individuals than in elderly individuals, but there
      was no age-related difference in SOL shear modulus. From the standpoint of an
      index reflecting muscle mechanical properties, it is suggested that the lower
      muscle shear moduli of RF and LG are the reason for the decreased explosive
      muscle strength in the lower extremity and the increased risk of falls for
      elderly individuals. 

PMID- 26314497
TI  - Radiology Education: Creating Tomorrow's Radiologists with Yesterday's Budgets!

PMID- 26314498
TI  - Continuous Certification Within Residency: An Educational Model.
AB  - Given that maintaining compliance with Maintenance of Certification is necessary
      for maintaining licensure to practice as a radiologist and provide quality
      patient care, it is important for radiology residents to practice fulfilling each
      part of the program during their training not only to prepare for success after
      graduation but also to adequately learn best practices from the beginning of
      their professional careers. This article discusses ways to implement continuous
      certification (called Continuous Residency Certification) as an educational model
      within the residency training program. 

PMID- 26314499
TI  - Effects of neonatal inflammation on the inflammatory and oxidative profile during
      experimental sepsis in adult life.
AB  - The present study aimed to evaluate the long-term effects of neonatal
      inflammation on the inflammatory and oxidative profile during experimental sepsis
      in adult life. Neonatal Balb/c mice received different treatments on day 10: LPS
      i.p. injection (100g/kg) (nLPS) or saline i.p. injection (nSal). As adults,
      fear/anxiety behavior was evaluated in the elevated plus maze. The following
      week, saline solution or LPS was administered and, after 12h, serum (inflammatory
      cytokines), liver (mitochondrial complexes and oxidative stress) and adrenal
      gland samples (angiotensin II type 1 and 2 receptors) were collected. There was
      an increase in the fear/anxiety behavior in the nLPS group. Neonatal
      administration of LPS increased the mRNA expression of the AT1 receptor and
      decreased the mRNA expression of the AT2 receptor in the adrenal glands of males.
      The complexes II and II-III increased in the nLPS saline male group when compared
      to control. The LPS administration in adult females, regardless of the neonatal
      treatment, induced a decrease of the glutathione enzyme activity. There were no
      differences in the inflammatory cytokines. The results showed that neonatal
      inflammation influenced mitochondrial respiratory chain metabolism and
      angiotensin II receptors in a sex-dependent manner. Balb/c mice fear and anxiety
      behaviors in adulthood were programmed by early life inflammatory stress. 

PMID- 26314501
TI  - Editorial: 21st Century Storm Chasers: Defining Macrophage Activation Syndrome.

PMID- 26314500
TI  - A novel thiol-reductase activity of Arabidopsis YUC6 confers drought tolerance
      independently of auxin biosynthesis.
AB  - YUCCA (YUC) proteins constitute a family of flavin monooxygenases (FMOs), with an
      important role in auxin (IAA) biosynthesis. Here we report that Arabidopsis
      plants overexpressing YUC6 display enhanced IAA-related phenotypes and exhibit
      improved drought stress tolerance, low rate of water loss and controlled ROS
      accumulation under drought and oxidative stresses. Co-overexpression of an IAA
      conjugating enzyme reduces IAA levels but drought stress tolerance is unaffected,
      indicating that the stress-related phenotype is not based on IAA overproduction.
      YUC6 contains a previously unrecognized FAD- and NADPH-dependent thiol-reductase
      activity (TR) that overlaps with the FMO domain involved in IAA biosynthesis.
      Mutation of a conserved cysteine residue (Cys-85) preserves FMO but suppresses TR
      activity and stress tolerance, whereas mutating the FAD- and NADPH-binding sites,
      that are common to TR and FMO domains, abolishes all outputs. We provide a
      paradigm for a single protein playing a dual role, regulating plant development
      and conveying stress defence responses. 

PMID- 26314502
TI  - Synergistic interactions of apigenin, naringin, quercetin and emodin on
      inhibition of 3T3-L1 preadipocyte differentiation and pancreas lipase activity.
AB  - The interactions of four natural compounds including apigenin, naringin, emodin
      and quercetin were investigated on inhibiting 3T3-L1 preadipocyte differentiation
      and pancreas lipase activity. Oil Red O staining was conducted to visualise and
      quantify lipid accumulation. The difference between experimental and calculated
      results was utilised for determining the interaction types. Interestingly, emodin
      synergistically interacted with the other three compounds, and the combination of
      emodin and apigenin exhibited the strongest synergistic effect in both
      differentiation and pancreas lipase assays. Results implied that the combination
      of apigenin and emodin may be regarded as a promising complementary therapy for
      management of overweight or obesity.

PMID- 26314503
TI  - Overeating, late dinner, and perceived stress in Japanese workers.
AB  - OBJECTIVES: This study examined relationships among overeating at dinner, dinner
      time, perceived stress, and strategies for coping with stress among Japanese
      workers. METHODS: In December 2012, 255 male Japanese workers at a leasing
      company completed a questionnaire about overeating (score range: 5-20), dinner
      time, perceived stress, and strategies for coping with stress. Each worker was
      sent an email with a link to a website, where their answers were collected.
      Relationships among overeating, dinner time, perceived stress, and stress-related
      coping strategies were investigated using two-way analysis of variance. RESULTS:
      The analyses of cross-sectional data revealed no differences in the overeating
      scores among those who ate dinner before 21:00 according to their level of
      perceived stress. However, those who ate dinner after 21:00 and reported feeling
      stressed tended to overeat at dinner (F(1, 237)=5.62, p=0.019). Additionally,
      those with perceived stress engaged in emotional expression involving others, and
      those without perceived stress tended to seek help to solve their problems and
      change their mood. We found no significant interactions involving the items
      related to strategies for coping with stress. CONCLUSION: This study found that
      overeating at dinner was related to dinner time and perceived stress.
      Additionally, the combination of a late dinner time and perceived stress
      reinforced overeating at dinner. The results of this study do not identify a
      coping strategy to prevent overeating.

PMID- 26314504
TI  - Exenatide reverses dysregulated microRNAs in high-fat diet-induced obese mice.
AB  - Exenatide has beneficial effects on insulin sensitivity in several animal models;
      however, its mechanism of action remains unclear. Furthermore, the relationship
      between the effect of exenatide on the changes in the relative abundance of
      microRNAs (miRNAs), which play a role in regulating glucose and lipid metabolism,
      is not fully understood. Therefore, we assessed the effect of exenatide on miRNA
      expression in a high-fat diet (HFD)-induced mouse model of obesity. Both HFD
      control and exenatide-treated HFD mice showed similar body weight gain and
      increase in beta-cell mass. Insulin levels were significantly lower in exenatide
      treated mice than in HFD control mice. The levels of miRNA-15a, 29c, 124a, and
      375 in the pancreas were significantly increased in HFD control mice.
      Furthermore, the levels of miRNA-29c, 124a, and 146a in the liver and miRNA-15a,
      29c, 124a, and 146a in the muscle were significantly increased. In contrast, the
      levels of miRNA-15a, 29c, 124a, and 375 in the serum were significantly
      decreased. These effects were reversed by treatment with exenatide. Our results
      provide experimental evidence that exenatide-mediated amelioration of insulin
      sensitivity is associated with antagonistic changes in the relative abundance of
      miRNA-15a, 29c, 124a, and 375 in tissues and serum, thus highlighting their
      usefulness as biomarkers for monitoring insulin sensitivity and response to
      exenatide treatment in experimental diabetes.

PMID- 26314505
TI  - Mental and Physical Health Needs of Lesbian, Gay, and Bisexual Clients in
      Substance Abuse Treatment.
AB  - OBJECTIVE: Lesbian, gay, and bisexual (LGB) orientation predicts greater
      substance use, treatment utilization, and poorer mental and physical health, but
      health needs of LGB individuals in substance abuse treatment remain largely
      unknown. The purpose of this study was to identify differences in mental and
      physical health needs of LGB individuals in substance abuse treatment. METHODS:
      Substance abuse treatment admissions data from the County of San Francisco were
      used in this investigation of differences in mental and physical health problems
      and service utilization between LGB (n=1,441) and heterosexual individuals
      (n=11,770). RESULTS: LGB individuals were more likely to have mental health
      diagnoses (adjORs ranging from 1.86 to 4.00) and current mental health
      prescription medications (adjORs from 1.79 to 4.99) than heterosexual
      counterparts. Gay and bisexual men and bisexual women but not lesbian women, were
      more likely to be receiving mental health treatment. Gay men and bisexual women
      were more likely than heterosexual counterparts to report physical health
      problems. Gay and bisexual men and bisexual women but not lesbian women were more
      likely to be receiving health care. There were no differences between LGB
      individuals and heterosexual counterparts in the number of emergency room visits
      or hospital overnight stays. DISCUSSION: This study found that LGB individuals
      entering substance abuse treatment have greater mental and physical health needs
      than heterosexual counterparts. Implications for healthcare integration,
      research, and practice are discussed.

PMID- 26314506
TI  - MiR-335 is involved in major depression disorder and antidepressant treatment
      through targeting GRM4.
AB  - Major depressive disorder (MDD) is a prevalent mood disorder. Treatment of MDD
      includes a variety of biopsychosocial approaches. Glutamate receptor,
      metabotropic 4 (GRM4) has been implicated in the regulation of MDD and it is seen
      as an attractive target for drug discovery and development. Here we reported
      using cellular assays and blood samples from MDD patients and showed that miR-335
      was downregulated in individuals with depression compared with healthy controls.
      Additionally, we confirmed that miR-335 can directly target GRM4, which can
      further regulated the expression of miR-335. Antidepressant drug treatment with
      citalopram can upregulate miR-335 expression and downregulate GRM4 expression.
      These results suggest that miR-335 is associated with the pathophysiology of
      depression and is a potential target for new antidepressant treatments. 

PMID- 26314507
TI  - Examining the association between Apolipoprotein E (APOE) and self-reported sleep
      disturbances in non-demented older adults.
AB  - We aimed to examine the association between Apolipoprotein E (APOE) and sleep
      disturbances. This is a cross-sectional study, from the Washington Heights-Inwood
      Community Aging Project (WHICAP). A total of 1944 non-demented older adults took
      part in the study. Sleep dysfunction was measured using sleep categories derived
      from the Medical Outcomes Study Sleep Scale. Genetic association between APOE
      epsilon4 genotype and sleep disturbances was assessed using unadjusted linear
      regression models. Secondary analyses were conducted adjusting for age, sex,
      education, ethnicity and body mass index (BMI). In the unadjusted model,
      individuals carrying the APOE-epsilon4 allele showed lower levels of snoring
      (beta=-0.02, SE=0.01, p=0.010) and sleep apnea (beta=-0.01, SE=0.01, p=0.037)
      when compared to non-epsilon4 carriers. After covariates' adjustment, epsilon4
      carriers demonstrated stronger association with lower levels of both snoring
      (beta=-0.02, SE=0.01, p=0.006), and sleep apnea (beta=-0.01, SE=0.01, p=0.018).
      Our results suggest that APOE-epsilon4 is associated with decreased problems in
      snoring and sleep apnea, in non-demented older adults. 

PMID- 26314508
TI  - Group cognitive remediation therapy for chronic schizophrenia: A randomized
      controlled trial.
AB  - Individual-level cognitive remediation therapy (CRT) has been shown to be
      effective for cognitive improvement and social function amelioration. Here, we
      aimed to test the efficacy of group-based CRT in Chinese subjects with
      schizophrenia. One-hundred and four inpatients were randomly assigned to either
      40 sessions of small-group CRT therapy or therapeutic contact-matched Musical and
      Dancing Therapy (MDT). Cognitive and social functioning, as well as clinical
      symptoms, were evaluated over the course of treatment. Specifically, cognitive
      function was evaluated using a battery of cognitive measurements, clinical
      symptoms were evaluated using the Positive and Negative Syndrome Scale, and
      social function was evaluated using the Nurse's Observation Scale for Inpatient
      Evaluation-30. All patients were evaluated pre- and post-treatment. Forty-four
      individuals in the CRT group and 46 in the MDT group completed all of the planned
      treatments and analyses. Cognitive functions, especially cognitive flexibility
      and memory, showed significant improvement in the CRT group over the course of
      the study. The MDT group also showed improvement in several cognitive flexibility
      assessments, but the degree of improvement was significantly greater in the CRT
      group. Several social-function factors exhibited a significant improvement in the
      CRT group, but not in the MDT group. Cognitive function improvement correlated
      positively with social function without predicting social function change. We
      conclude that group-based CRT is an effective and promising therapy.

PMID- 26314509
TI  - alpha-Dendrotoxin inhibits the ASIC current in dorsal root ganglion neurons from
      rat.
AB  - Dendrotoxins are a group of peptide toxins purified from the venom of several
      mamba snakes. alpha-Dendrotoxin (alpha-DTx, from the Eastern green mamba
      Dendroaspis angusticeps) is a well-known blocker of voltage-gated K(+) channels
      and specifically of K(v)1.1, K(v)1.2 and K(v)1.6. In this work we show that alpha
      DTx inhibited the ASIC currents in DRG neurons (IC50=0.8 MUM) when continuously
      perfused during 25 s (including a 5 s pulse to pH 6.1), but not when co-applied
      with the pH drop. Additionally, we show that alpha-DTx abolished a transient
      component of the outward current that, in some experiments, appeared immediately
      after the end of the acid pulse. Our data indicate that alpha-DTx inhibits ASICs
      in the high nM range while some Kv are inhibited in the low nM range. The alpha
      DTx selectivity and its potential interaction with ASICs should be taken in
      consideration when DTx is used in the high nM range.

PMID- 26314510
TI  - Action of thymol on spontaneous excitatory transmission in adult rat spinal
      substantia gelatinosa neurons.
AB  - Thymol, which is contained in thyme essential oil, has various actions including
      antinociception and nerve conduction inhibition. Although thymol activates
      transient receptor potential (TRP) channels expressed in heterologous cells, it
      remains to be examined whether this is so in native neurons. It has not yet been
      examined how thymol affects synaptic transmission. In order to know how thymol
      modulates excitatory transmission with a focus on TRP activation, we investigated
      its effect on glutamatergic spontaneous excitatory transmission in lamina II
      (substantia gelatinosa; SG) neurons with which nerve terminals expressing TRP
      channels make synaptic contacts. The experiment was performed by using the blind
      whole-cell patch-clamp technique in adult rat spinal cord slices. Superfusing
      thymol (1 mM) for 3 min reversibly increased the frequency of spontaneous
      excitatory postsynaptic current (sEPSC) with a minimal increase in its amplitude
      in all neurons examined. Seventy-seven% of the neurons produced an outward
      current at a holding potential of -70 mV. The sEPSC frequency increase and
      outward current produced by thymol were concentration-dependent with almost the
      same half-maximal effective concentration (EC50) values of 0.18 and 0.14 mM,
      respectively. These activities were repeated at a time interval of 30 min,
      although the sEPSC frequency increase but not outward current recovered with a
      slow time course. Voltage-gated Na(+)-channel blocker tetrodotoxin did not affect
      the thymol activities. The sEPSC frequency increase was inhibited by TRPA1
      antagonist HC-030031 but not TRPV1 and TRPM8 antagonist (capsazepine and BCTC,
      respectively), while these antagonists had no effect on the outward current. This
      was so, albeit the two thymol activities had similar EC50 values. It is concluded
      that thymol increases the spontaneous release of L-glutamate onto SG neurons by
      activating TRPA1 channels while producing an outward current without TRP
      activation. Considering that the SG plays a pivotal role in modulating
      nociceptive transmission from the periphery, these actions of thymol could
      contribute to at least a part of its antinociceptive effect.

PMID- 26314511
TI  - Influence of contralateral homologous cortices on motor cortical reorganization
      after brachial plexus injuries in rats.
AB  - Brachial plexus injuries induce corresponding cortical representations to be
      occupied by adjacent cortices. The purpose of this study was to clarify if
      contralateral homologous motor regions of adjacent cortices influence occupation
      of deafferented motor cortex. 36 rats were divided into 3 groups of 12 each. In
      group 1, total brachial plexus root avulsion (tBPRA) was made on the left side.
      In group 2, rats underwent left tBPRA combined with corpus callosum transection
      (CCX). In group 3, only CCX was performed. 6 rats in each group were used for
      intracortical microstimulation (ICMS) to map representations of motor cortex in
      the right hemisphere at 7 days and the other 6 rats, at 3 months. 18 more rats
      without any operation underwent ICMS, with 6 each taken to serve as normal
      control for motor cortical representations' changes caused by different surgery.
      Results showed that in groups 1 and 2, sites for motor cortical representations
      of vibrissae, of neck and of the hindlimb was statistically more than that of
      control, respectively, and statistically more sites were found at 3 months than
      at 7 days, respectively. At the two time points, sites for vibrissa cortices and
      that for the hindlimb were statistically more in group 2 than in group 1,
      respectively. CCX alone did not induce change of site number for motor cortical
      representations. We conclude that after tBPRA, contralateral homologous motor
      cortices may, to some extent, prevent neighboring cortices from encroachment on
      motor cortical representations of the brachial plexus. 

PMID- 26314512
TI  - DNA methylation of the GC box in the promoter region mediates isolation rearing
      induced suppression of srd5a1 transcription in the prefrontal cortex.
AB  - The levels of allopregnanolone (ALLO), a neurosteroid, in brain and serum are
      related to severity of depression and anxiety. Steroid 5alpha-reductase type I is
      the rate-limiting enzyme in ALLO biosynthesis and plays an important role in
      control of the ALLO level in mammalian brain. In this study, we examined an
      epigenetic mechanism for transcriptional regulation of srd5a1, which codes for
      steroid 5alpha-reductase type I, using isolation-reared mice. The mRNA level of
      srd5a1 was decreased in the prefrontal cortex (PFC) in isolation-reared mice.
      Rearing in social isolation increased methylation of cytosines at -82 and -12 bp
      downstream of the transcription start site, which are located in a GC box element
      in the promoter region of srd5a1. Binding of Sp1, a ubiquitous transcription
      factor, to the GC box was decreased in the promoter region of srd5a1 in the PFC
      in isolation-reared mice. Site-specific methylation at cytosine -12 of a srd5a1
      promoter-luciferase reporter construct, but not that of cytosine -82,
      downregulated the promoter activity of srd5a1. These findings suggest that
      transcription of srd5a1 in brain is regulated by environmental factor-induced
      cytosine methylation in the promoter region. This finding could contribute to
      development of antidepressant and anxiolytic agents.

PMID- 26314513
TI  - Remote ischemic preconditioning: Simple method but unknown mechanisms.

PMID- 26314514
TI  - Electromagnetically Induced Entanglement.
AB  - Quantum entanglement provides an essential resource for quantum computation,
      quantum communication, and quantum network. How to conveniently and efficiently
      produce entanglement between bright light beams presents a challenging task to
      build realistic quantum information processing networks. Here, we present an
      efficient and convenient way to realize a novel quantum phenomenon, named
      electromagnetically induced entanglement, in the conventional Lambda-type three
      level atomic system driven by a strong pump field and a relatively weak probe
      field. Nearly perfect entanglement between the two fields can be achieved with a
      low coherence decay rate between the two lower levels, high pump-field intensity,
      and large optical depth of the atomic ensemble. The physical origin is quantum
      coherence between the lower doublet produced by the pump and probe fields,
      similar to the well-known electromagnetically induced transparency. This method
      would greatly facilitate the generation of nondegenerate narrow-band continuous
      variable entanglement between bright light beams by using only coherent laser
      fields, and may find potential and broad applications in realistic quantum
      information processing. 

PMID- 26314515
TI  - Chronic administration of Glucagon-like peptide-1 receptor agonists improves
      trabecular bone mass and architecture in ovariectomised mice.
AB  - Some anti-diabetic therapies can have adverse effects on bone health and increase
      fracture risk. In this study, we tested the skeletal effects of chronic
      administration of two Glucagon-like peptide-1 receptor agonists (GLP-1RA),
      increasingly used for type 2 diabetes treatment, in a model of osteoporosis
      associated bone loss and examined the expression and activation of GLP-1R in bone
      cells. Mice were ovariectomised (OVX) to induce bone loss and four weeks later
      they were treated with Liraglutide (LIR) 0.3mg/kg/day, Exenatide (Ex-4) 10
      MUg/kg/day or saline for four weeks. Mice were injected with calcein and alizarin
      red prior to euthanasia, to label bone-mineralising surfaces. Tibial micro
      architecture was determined by micro-CT and bone formation and resorption
      parameters measured by histomorphometric analysis. Serum was collected to measure
      calcitonin and sclerostin levels, inhibitors of bone resorption and formation,
      respectively. GLP-1R mRNA and protein expression were evaluated in the bone, bone
      marrow and bone cells using RT-PCR and immunohistochemistry. Primary osteoclasts
      and osteoblasts were cultured to evaluate the effect of GLP-1RA on bone
      resorption and formation in vitro. GLP-1RA significantly increased trabecular
      bone mass, connectivity and structure parameters but had no effect on cortical
      bone. There was no effect of GLP-1RA on bone formation in vivo but an increase in
      osteoclast number and osteoclast surfaces was observed with Ex-4. GLP-1R was
      expressed in bone marrow cells, primary osteoclasts and osteoblasts and in late
      osteocytic cell line. Both Ex-4 and LIR stimulated osteoclastic differentiation
      in vitro but slightly reduced the area resorbed per osteoclast. They had no
      effect on bone nodule formation in vitro. Serum calcitonin levels were increased
      and sclerostin levels decreased by Ex-4 but not by LIR. Thus, GLP-1RA can have
      beneficial effects on bone and the expression of GLP-1R in bone cells may imply
      that these effects are exerted directly on the tissue.

PMID- 26314516
TI  - Response to bone-D-15-00337.

PMID- 26314517
TI  - Emerging therapeutic concepts for muscle and bone preservation/formation.

PMID- 26314519
TI  - Practice patterns and postoperative complications before and after US Food and
      Drug Administration safety communication on power morcellation.
AB  - BACKGROUND: In April 2014, the US Food and Drug Administration (FDA) published
      its first safety communication discouraging "the use of laparoscopic power
      morcellation during hysterectomy or myomectomy for the treatment of women with
      uterine fibroids." Due to the concern of worsening outcomes for patients with
      occult uterine malignancy, specifically uterine leiomyosarcoma, the FDA
      recommended a significant change to existing surgical planning, patient consent,
      and surgical technique in the United States. OBJECTIVE: We sought to report
      temporal trends in surgical approach to hysterectomy and postoperative
      complications before and after the April 17, 2014, FDA safety communication
      concerning the use of power morcellation during myomectomy or hysterectomy. STUDY
      DESIGN: A retrospective cohort study was performed with patients undergoing
      hysterectomy for benign indications in the Michigan Surgical Quality
      Collaborative from Jan. 1, 2013, through Dec. 31, 2014. The rates of abdominal,
      laparoscopic, and vaginal hysterectomy, as well as the rates of major
      postoperative complications and 30-day hospital readmissions and reoperations,
      were compared before and after April 17, 2014, the date of the original FDA
      safety communication. Major postoperative complications included blood
      transfusions, vaginal cuff infection, vaginal cuff dehiscence, ureteral
      obstruction, vesicovaginal fistula, deep and organ space surgical site infection,
      acute renal failure, respiratory failure, sepsis, pulmonary embolism, deep vein
      thrombosis requiring therapy, cerebral vascular accident, cardiac arrest, and
      death. We calculated the median episode cost related to hysterectomy readmissions
      using Michigan Value Collaborative data. Analyses were performed using robust
      multivariable multinomial and logistic regression models. RESULTS: There were
      18,299 hysterectomies available for analysis during the study period. In all,
      2753 cases were excluded due to an indication for cancer, cervical dysplasia, or
      endometrial hyperplasia, and 174 cases were excluded due to missing covariate
      data. Compared to the 15 months preceding the FDA safety communication, in the 8
      months afterward, utilization of laparoscopic hysterectomies decreased by 4.1% (P
      = .005) and both abdominal and vaginal hysterectomies increased (1.7%, P = .112
      and 2.4%, P = .012, respectively). Major surgical complications not including
      blood transfusions significantly increased after the date of the FDA safety
      communication, from 2.2-2.8% (P = .015), and the rate of hospital readmission
      within 30 days also increased from 3.4-4.2% (P = .025). The rate of all major
      surgical complications or hospital reoperations did not change significantly
      after the date of the FDA communication (P = .177 and P = .593, respectively).
      The median risk-adjusted total episode cost for readmissions was $5847
      (interquartile range $5478-10,389). CONCLUSION: Following the April 2014 FDA
      safety communication regarding power morcellation, utilization of minimally
      invasive hysterectomy decreased, and major surgical, nontransfusion complications
      and 30-day hospital readmissions increased.

PMID- 26314518
TI  - Injectable silk-based biomaterials for cervical tissue augmentation: an in vitro
      study.
AB  - BACKGROUND: Cerclage therapy is an important treatment option for preterm birth
      prevention. Several patient populations benefit from cerclage therapy including
      patients with a classic history of cervical insufficiency; patients who present
      with advanced cervical dilation prior to viability; and patients with a history
      of preterm birth and cervical shortening. Although cerclage is an effective
      treatment option in some patients, it can be associated with limited efficacy and
      procedure complications. Development of an alternative to cerclage therapy would
      be an important clinical development. Here we report on an injectable, silk
      protein-based biomaterial for cervical tissue augmentation. The rationale for the
      development of an injectable biomaterial is to restore the native properties of
      cervical tissue. While cerclage provides support to the tissue, it does not
      address excessive tissue softening, which is a central feature of the
      pathogenesis of cervical insufficiency. Silk protein-based hydrogels, which are
      biocompatible and naturally degrade in vivo, are suggested as a platform for
      restoring the native properties of cervical tissue and improving cervical
      function. OBJECTIVE: We sought to study the properties of an injectable, silk
      based biomaterial for potential use as an alternative treatment for cervical
      insufficiency. These biomaterials were evaluated for mechanical tunability,
      biocompatibility, facile injection, and in vitro degradation. STUDY DESIGN: Silk
      protein solutions were cross-linked by an enzyme catalyzed reaction to form
      elastic biomaterials. Biomaterials were formulated to match the native physical
      properties of cervical tissue during pregnancy. The cell compatibility of the
      materials was assessed in vitro using cervical fibroblasts, and biodegradation
      was evaluated using concentrated protease solution. Tissue augmentation or
      bulking was demonstrated using human cervical tissue from nonpregnant
      hysterectomy specimens. Mechanical compression tests measured the tissue
      stiffness as a function of the volume of injected biomaterial. RESULTS: Silk
      protein concentration, molecular weight, and concentration of cross-linking agent
      were varied to generate biomaterials that functioned from hard gels to viscous
      fluids. Biomaterials that matched the mechanical features of cervical tissues
      were chosen for further study. Cervical fibroblasts cultured on these
      biomaterials were proliferative and metabolically active over 6 days.
      Biomaterials were degraded in protease solution, with rate of mass loss dependent
      on silk protein molecular weight. Injection of cervical tissue samples with 100
      MUL of the biomaterial resulted in a significant volume increase (22.6% +/- 8.8%,
      P < .001) with no significant change in tissue stiffness. CONCLUSION:
      Cytocompatible, enzyme cross-linked silk protein biomaterials show promise as a
      tissue bulking agent. The biomaterials were formulated to match the native
      mechanical properties of human cervical tissue. These biomaterials should be
      explored further as a possible alternative to cerclage for providing support to
      the cervix during pregnancy.

PMID- 26314520
TI  - Reproductive coercion: uncloaking an imbalance of social power.
AB  - Reproductive coercion involves behavior that interferes with contraceptive and
      pregnancy choices of women and occasionally men. This includes birth control
      sabotage (intentional destruction of a woman's chosen method of contraception),
      pregnancy pressure (behaviors to coerce pregnancy against one's wishes), and
      pregnancy coercion (threats to direct the outcome of a pregnancy). All are
      associated with serious reproductive consequences including unintended pregnancy,
      abortion, sexually transmitted infections, poor pregnancy outcomes, and
      psychological trauma. This article presents an overview of the recent literature
      surrounding reproductive coercion and how it relates to the reproductive health
      outcomes of women, adolescents, and the lesbian, gay, bisexual, and transgender
      community. Men's experience with reproductive coercion will also be discussed.
      Clinical implications and evidence-based strategies for assessment and
      intervention will be identified. 

PMID- 26314521
TI  - Identification and characterization of proteins with phenoloxidase-like
      activities in the sea urchin Strongylocentrotus nudus.
AB  - Three proteins with PO-like activities in the coelomocytes of sea urchin
      Strongylocentrotus nudus were identified using electrophoretic method and named
      as SnPO1, SnPO2 and SnPO3 according to their molecular mass from high to low. The
      SnPOs were characterized for substrate specificity and the effects of
      temperature, pH, divalent metal ions and inhibitors on PO activities. They showed
      oxidative activities to L-3,4-dihydroxyphenylalanine. (l-DOPA), dopamine and
      hydroquinone, but failed to oxidize tyrosine, which illustrated the three
      proteins had laccase-like PO activities. The optimum temperature for the
      activities of SnPO1, SnPO2 and SnPO3 was 75  degrees C, 70  degrees C, 40 
      degrees C, and the optimum pH was 7.0, 9.0, 8.0, respectively. The SnPOs were
      notably activated after being incubated in boiled water for 60 min, suggesting
      that the three proteins are thermophilic. The activity of SnPO1 was greatly
      enhanced by Cu(2+), Mn(2+) and Fe(2+) and inhibited by Pb(2+), Cd(2+), EDTA,
      DETC, sodium sulfite and ascorbic acid, but SnPO2 and SnPO3 were not obviously
      affected by Pb(2+) and Cd(2+), suggesting the three proteins are copper
      containing, and the catalytic properties of SnPO1 might be different from those
      of SnPO2 and SnPO3. Taken together, SnPO1, SnPO2 and SnPO3 might play different
      roles in the immune and physiological processes of S. nudus.

PMID- 26314522
TI  - The role of oncoprotein NM23 gene from Exopalaemon carinicauda is response to
      pathogens challenge and ammonia-N stress.
AB  - Oncoprotein NM23, as a family of genes encoding the nucleoside diphosphate (NDP)
      kinase, plays important roles in bioenergetics, DNA replication, differentiation
      and tumor metastasis. In this study, a full-length cDNA of NM23 (designated
      EcNM23) was cloned from Exopalaemon carinicauda by using rapid amplification of
      cDNA ends (RACE) approaches. The full-length cDNA of EcNM23 was 755 bp, which
      contains an open reading frame (ORF) of 518 bp, encoding a 175 amino-acid
      polypeptide with the predicted molecular weight of 19.60 kDa and estimated
      isoelectric point of 7.67. The deduced amino acid sequence of EcNM23 shared high
      identity (86%-93%) with that of other crustaceans. a NDP kinase super family
      signature was identified in E. carinicauda EcNM23. Quantitative real-time RT-qPCR
      analysis indicated that EcNM23 was expressed in all the examined tissues with the
      high expression level in hemocytes and ovary. The EcNM23 expression in immune
      related tissues changed rapidly and reached peak at different time after
      pathogens (Vibrio parahaemolyticus and WSSV) challenge and ammonia-N stress
      treatment. The results suggested that EcNM23 might be associated with the immune
      defenses to pathogens infection and ammonia-N stress in E. carinicauda.

PMID- 26314523
TI  - Enhanced immune response and resistance to edwardsiellosis following dietary
      chitooligosaccharide supplementation in the olive flounder (Paralichthys
      olivaceus).
AB  - This study was conducted to evaluate the effects of dietary chitooligosaccharide
      (COS) supplementation on peripheral leukocyte count, head kidney leukocyte
      phagocytic rate, phagocytic index, respiratory burst activity, serum lysozyme
      activity, and immune protection in Paralichthys olivaceus. A total of 300
      flounder with an average body weight of 80-100 g were randomly assigned into four
      dietary groups: (I) basic diet (control), basic diet containing (II) 0.5% COS,
      and (III) 1% COS, fed continuously for 28 d, and (IV) basic diet containing 1%
      COS fed in 14 d intervals. Continuous feeding of 0.5% and 1% COS diets for 28 d
      significantly increased the number of peripheral leukocytes, head kidney
      leukocyte phagocytic rate, phagocytic index, respiratory burst activity, and
      serum lysozyme activity (P < 0.05 or P < 0.01). After a 10 d Edwardsiella tarda
      challenge, the immune protection rates in the 0.5% and 1% COS groups were 30% and
      60%, respectively. No control fish survived the E. tarda challenge treatment.
      Most immune indices were slightly lower after removal of COS from the diet for 14
      d, but all immune indices were observed to recover after another 14 d of COS
      supplementation. This study demonstrates that supplementation of a basic diet
      with COS enhances the non-specific immune response and improves survival rates
      following infection with E. tarda in P. olivaceus. An optimized interval feeding
      strategy with diets containing 1% COS may have potential applications in the
      prevention of disease in aquacultured P. olivaceus.

PMID- 26314524
TI  - Catalase eliminates reactive oxygen species and influences the intestinal
      microbiota of shrimp.
AB  - Intestinal innate immune response is an important defense mechanism of animals
      and humans against external pathogens. The mechanism of microbiota homeostasis in
      host intestines has been well studied in mammals and Drosophila. The reactive
      oxygen species (ROS) and antimicrobial peptides have been reported to play
      important roles in homeostasis. However, how to maintain the microbiota
      homeostasis in crustacean intestine needs to be elucidated. In this study, we
      identified a novel catalase (MjCAT) involved in ROS elimination in kuruma shrimp,
      Marsupenaeus japonicus. MjCAT mRNA was widely distributed in hemocytes, heart,
      hepatopancreas, gills, stomach, and intestine. After the shrimp were challenged
      with pathogenic bacteria via oral infection, the expression level of MjCAT was
      upregulated, and the enzyme activity was increased in the intestine. ROS level
      was also increased in the intestine at early time after oral infection and
      recovered rapidly. When MjCAT was knocked down by RNA interference (RNAi), high
      ROS level maintained longer time, and the number of bacteria number was declined
      in the shrimp intestinal lumen than those in the control group, but the survival
      rate of the MjCAT-RNAi shrimp was declined. Further study demonstrated that the
      intestinal villi protruded from epithelial lining of the intestinal wall were
      damaged by the high ROS level in MjCAT-knockdown shrimp. These results suggested
      that MjCAT participated in the intestinal host-microbe homeostasis by regulating
      ROS level.

PMID- 26314525
TI  - Physical Fitness, Physical Activity, Exercise Training, and Atrial Fibrillation:
      First the Good News, Then the Bad.

PMID- 26314526
TI  - Incidence of Atrial Fibrillation and Relationship With Cardiovascular Events,
      Heart Failure, and Mortality: A Community-Based Study From the Netherlands.
AB  - BACKGROUND: Important improvements have been made in treatment of diseases
      associated with atrial fibrillation (AF), such as hypertension, myocardial
      infarction, and heart failure. Incidence rates and risk factors may have changed
      with the aging of the population and changing lifestyles. Currently, the risk for
      AF is only partially explained, possibly because of differences between older
      cohorts and contemporary populations. OBJECTIVES: This study investigated the
      incidence of AF in a contemporary cohort in the Netherlands, together with
      comorbidities associated with AF and associations of AF with cardiovascular
      outcomes. METHODS: Incident AF was ascertained for hospital and study
      electrocardiograms in 8,265 participants of the PREVEND (Prevention of Renal and
      Vascular End-Stage Disease) study in Groningen, the Netherlands. RESULTS: During
      9.7 +/- 2.3 years of follow-up, 265 participants developed AF, with a resulting
      overall AF incidence of 3.3 per 1,000 person-years. Advancing age, male sex,
      antihypertensive drug use, higher body mass index, previous myocardial
      infarction, and previous stroke were associated with AF. After multivariable
      adjustment, AF was associated with cardiovascular events (hazard ratio [HR]:
      2.24; 95% confidence interval [CI]: 1.06 to 4.75; p = 0.035), heart failure with
      either reduced or preserved ejection fraction (HR: 4.52; 95% CI: 2.02 to 10.09; p
      < 0.001), and all-cause mortality (HR: 3.02; 95% CI: 1.73 to 5.27; p < 0.001).
      CONCLUSIONS: The incidence of AF in the present cohort was comparable to that
      shown in data of older studies. Obesity has become a major risk factor for
      incident AF. Although overall cardiovascular event rates were lower in the
      present study, the present study confirms the association of incident AF with
      such events.

PMID- 26314527
TI  - Observing the Obvious.

PMID- 26314528
TI  - Initial Experience of Transcatheter Mitral Valve Replacement With a Novel
      Transcatheter Mitral Valve: Procedural and 6-Month Follow-Up Results.
AB  - BACKGROUND: There are scarce data available on transcatheter mitral valve
      replacement (TMVR), and these have been limited to procedural results, with no
      follow-up status reported. OBJECTIVES: The goal of this study was to evaluate the
      feasibility, procedural results, and 6-month follow-up outcomes after TMVR with a
      mitral transcatheter heart valve (Fortis, Edwards Lifesciences, Irvine,
      California). METHODS: We report a series of 3 patients (mean age 71 +/- 9 years,
      2 men) who had TMVR under a compassionate clinical use program. All patients
      treated had functional mitral regurgitation (MR) secondary to ischemic
      cardiomyopathy (prior bypass surgery in all cases; left ventricular ejection
      fraction between 25% and 30%) and were considered to be at very high surgical
      risk (mean Society of Thoracic Surgeons score: 9.3). RESULTS: The procedure was
      performed through the transapical approach, and the valve was successfully
      implanted in all cases, with no major complications. At hospital discharge,
      echocardiographic evaluation revealed trace residual MR in 2 patients and no MR
      in 1 patient. The mean transvalvular mitral gradient was <=4 mm Hg in all
      patients. At the 3-month follow-up, the valve function remained unchanged, and
      transesophageal echocardiography and computed tomography showed no structural
      failures. All patients had improvements in functional status, in exercise
      capacity as evaluated by 6-min walk test, and in quality of life. At 6-month
      follow-up, all patients remain alive, without hospital readmission for heart
      failure and with New York Heart Association functional class <=II. CONCLUSIONS:
      TMVR with this valve is feasible and is associated with good outcomes. Optimal
      valve functional results were obtained acutely and were sustained at 6-month
      follow-up in all patients. Further studies with a larger number of patients and
      longer follow-up are warranted.

PMID- 26314529
TI  - TMVR: Continuing the Paradigm Shift in Valvular Heart Disease Therapy: Hype or
      Hope?

PMID- 26314530
TI  - Precision Medicine in Patients With Resistant Hypertension and Obstructive Sleep
      Apnea: Blood Pressure Response to Continuous Positive Airway Pressure Treatment.
AB  - BACKGROUND: In patients with resistant hypertension (RH) and obstructive sleep
      apnea (OSA), the blood pressure response to continuous positive airway pressure
      (CPAP) treatment is highly variable and could be associated with differential
      micro-ribonucleic acid (miRNA) profiles. Currently, no available methods exist to
      identify patients who will respond favorably to CPAP treatment. OBJECTIVES: The
      aim of this study was to identify plasma miRNA profiles that predict blood
      pressure responses to CPAP treatment. METHODS: Cardiovascular system-focused
      circulating miRNA expression was evaluated in plasma samples using an 84-miRNA
      array among patients with RH and OSA at baseline and after 3 months of adherent
      CPAP use. Pathway analysis and miRNA target gene enrichment were performed in
      silico. Plasma levels of peptides and hormones related to cardiovascular function
      were also measured. RESULTS: The OSA responder group exhibited blood pressure
      decreases exceeding the observed median (>4.5 mm Hg) after CPAP, which were not
      present in the nonresponder group (<=4.5 mm Hg) (p < 0.01). Three miRNAs provided
      a discriminatory predictive model for such a favorable blood pressure response to
      CPAP (area under the curve: 0.92; p = 0.01). Additionally, CPAP treatment
      significantly altered a total of 47 plasma miRNAs and decreased aldosterone-to
      renin ratios in the responder group (p = 0.016) but not in the nonresponder
      group. CONCLUSIONS: A singular pre-CPAP treatment cluster of 3 plasma miRNAs
      predicts blood pressure responses to CPAP treatment in patients with RH and OSA.
      CPAP treatment is accompanied by changes in cardiovascular system-related miRNAs
      that may potentially influence the risk for cardiovascular disease among patients
      with OSA and RH. (Effect of Continuous Positive Airway Pressure [CPAP] Treatment
      in the Control of Refractory Hypertension; NCT00616265).

PMID- 26314531
TI  - Measuring Blood microRNAs to Provide Personalized Advice to Sleep Apnea Patients
      With Resistant Hypertension: Dreaming the Future.

PMID- 26314533
TI  - The Shifting Pendulum for DAPT After PCI: Balancing Long-Term Risks for Bleeding
      and Thrombosis.

PMID- 26314532
TI  - Incidence, Predictors, and Impact of Post-Discharge Bleeding After Percutaneous
      Coronary Intervention.
AB  - BACKGROUND: The incidence, predictors, and prognostic impact of post-discharge
      bleeding (PDB) after percutaneous coronary intervention (PCI) with drug-eluting
      stent (DES) implantation are unclear. OBJECTIVES: This study sought to
      characterize the determinants and consequences of PDB after PCI. METHODS: The
      prospective ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting
      Stents) study was used to determine the incidence and predictors of clinically
      relevant bleeding events occurring within 2 years after hospital discharge. The
      effect of PDB on subsequent 2-year all-cause mortality was estimated by time
      adjusted Cox proportional hazards regression. RESULTS: Among 8,582 "all-comers"
      who underwent successful PCI with DES in the ADAPT-DES study, PDB occurred in 535
      of 8,577 hospital survivors (6.2%) at a median time of 300 days (interquartile
      range: 130 to 509 days) post-discharge. Gastrointestinal bleeding (61.7%) was the
      most frequent source of PDB. Predictors of PDB included older age, lower baseline
      hemoglobin, lower platelet reactivity on clopidogrel, and use of chronic oral
      anticoagulation therapy. PDB was associated with higher crude rates of all-cause
      mortality (13.0% vs. 3.2%; p < 0.0001). Following multivariable adjustment, PDB
      was strongly associated with 2-year mortality (hazard ratio [HR]: 5.03; p <
      0.0001), with an effect size greater than that of post-discharge myocardial
      infarction (PDMI) (HR: 1.92; p = 0.009). CONCLUSIONS: After successful PCI with
      DES in an unrestricted patient population, PDB is not uncommon and has a strong
      relationship with subsequent all-cause mortality, greater that that associated
      with PDMI. Efforts to reduce PDB may further improve prognosis after successful
      DES implantation. (Assessment of Dual Antiplatelet Therapy With Drug-Eluting
      Stents [ADAPT-DES]; NCT00638794).

PMID- 26314534
TI  - The CardioMetabolic Health Alliance: Working Toward a New Care Model for the
      Metabolic Syndrome.
AB  - The Cardiometabolic Think Tank was convened on June 20, 2014, in Washington, DC,
      as a "call to action" activity focused on defining new patient care models and
      approaches to address contemporary issues of cardiometabolic risk and disease.
      Individual experts representing >20 professional organizations participated in
      this roundtable discussion. The Think Tank consensus was that the metabolic
      syndrome (MetS) is a complex pathophysiological state comprised of a cluster of
      clinically measured and typically unmeasured risk factors, is progressive in its
      course, and is associated with serious and extensive comorbidity, but tends to be
      clinically under-recognized. The ideal patient care model for MetS must
      accurately identify those at risk before MetS develops and must recognize
      subtypes and stages of MetS to more effectively direct prevention and therapies.
      This new MetS care model introduces both affirmed and emerging concepts that will
      require consensus development, validation, and optimization in the future. 

PMID- 26314535
TI  - Critical Questions About Left-Sided Infective Endocarditis.
AB  - Research in different topics in cardiovascular medicine is evolving rapidly.
      However, this is not the case for endocarditis, despite its being the
      cardiovascular disease with the highest mortality and, at the same time, the
      entity with relatively less scientific evidence supporting its treatment. Many
      problems are delaying research: it is an uncommon disease, few multicenter
      registries are ongoing, financing for research in this topic is lacking,
      randomization is costly, difficult, and considered unethical by some, and
      conclusions coming from propensity score analysis are taken as if they came from
      randomized trials. In this review, we put forward the main issues in need of
      evidence and propose a different approach to advance the understanding of left
      sided infective endocarditis. We summarize the limited evidence available, the
      questions that are pending, and how we should proceed to answer them. 

PMID- 26314536
TI  - The Vulnerable Patient: Providing a Lens Into the Interconnected Diseases of the
      Heart and Brain.

PMID- 26314537
TI  - Mentorship, Leadership, and Teamwork: Harnessing the Power of Professional
      Societies to Develop Nonclinical Competencies.

PMID- 26314538
TI  - Association Between High Levels of Physical Exertion, Anger, and Anxiety
      Immediately Before Myocardial Infarction With Mortality During 10-Year Follow-Up.

PMID- 26314539
TI  - Lifetime Risk of Pulmonary Hypertension for All Patients After Shunt Closure.

PMID- 26314540
TI  - Genetic Variation in NPC1L1 and Risk of Gallstone Disease.

PMID- 26314541
TI  - Reply: Genetic Variation in NPC1L1 and Risk of Gallstone Disease.

PMID- 26314542
TI  - Duration of Triple Therapy in Patients Requiring Oral Anticoagulation After Drug
      Eluting Stent Implantation.

PMID- 26314543
TI  - Reply: Duration of Triple Therapy in Patients Requiring Oral Anticoagulation
      After Drug-Eluting Stent Implantation.

PMID- 26314544
TI  - Ultra-low voltage and ultra-low power consumption nonvolatile operation of a
      three-terminal atomic switch.
AB  - Nonvolatile three-terminal operation, with a very small range of bias sweeping (
      80 to 250 mV), a high on/off ratio of up to six orders of magnitude, and a very
      small gate leakage current (<1 pA), is demonstrated using an Ag (gate)/Ta2 O5
      (ionic transfer layer)/Pt (source), Pt (drain) three-terminal atomic switch
      structure. 

PMID- 26314545
TI  - Voltage-morphology coupling in biomimetic membranes: dynamics of giant vesicles
      in applied electric fields.
AB  - An electric potential difference across the plasma membrane is common to all
      living cells and is essential to physiological functions such as the generation
      of action potentials for cell-to-cell communication. While the basics of cell
      electrical activity are well established (e.g. the Hodgkin-Huxley model of the
      action potential), the reciprocal coupling of voltage and membrane deformation
      has received limited attention. In recent years, studies of biomimetic membranes
      in externally applied electric fields have revealed a plethora of intriguing
      dynamics (formation of edges, pearling, and phase separation) that challenge the
      current understanding of membrane electromechanics. 

PMID- 26314546
TI  - Effect of J coupling on 1.3-ppm lipid methylene signal acquired with localised
      proton MRS at 3 T.
AB  - The purpose of this work was to investigate the effect of J-coupling interactions
      on the quantification and T2 determination of 1.3-ppm lipid methylene protons at
      3 T. The response of the 1.3-ppm protons of hexanoic, heptanoic, octanoic,
      linoleic and oleic acid was measured as a function of point-resolved spectroscopy
      (PRESS) and stimulated echo acquisition mode (STEAM) TE. In addition, a narrow
      bandwidth refocusing PRESS sequence designed to rewind J-coupling evolution of
      the 1.3-ppm protons was applied to the five fatty acids, to corn oil and to
      tibial bone marrow of six healthy volunteers. Peak areas were plotted as a
      function of TE, and data were fitted to monoexponentially decaying functions to
      determine Mo (the extrapolated area for TE = 0 ms) and T2 values. In phantoms,
      rewinding J-coupling evolution resulted in 198%, 64%, 44%, 20% and 15% higher T2
      values for heptanoic, octanoic, linoleic and oleic acid, and corn oil,
      respectively, compared with those obtained with standard PRESS. The narrow
      bandwidth PRESS sequence also resulted in significant changes in Mo , namely 
      77%, -22%, 28%, 23% and 28% for heptanoic, octanoic, linoleic and oleic acid, and
      corn oil, respectively. T2 values obtained with STEAM were closer to the values
      measured with narrow-bandwidth PRESS. On average, in tibial bone marrow (six
      volunteers) rewinding J-coupling evolution resulted in 21% +/- 3% and 9 % +/- 1%
      higher Mo and T2 values, respectively. This work demonstrates that the
      consequence of neglecting to consider scalar coupling effects on the
      quantification of 1.3-ppm lipid methylene protons and their T2 values is not
      negligible. The linoleic and oleic acid T2 results indicate that T2 measures of
      lipids with standard MRS techniques are dependent on lipid composition.

PMID- 26314547
TI  - [The first experiences with colorectal laparoscopic surgery in Spain. Valencia,
      November 1991].
AB  - The development of laparoscopic colon surgery in Spain has spread quickly since
      its beginnings at the end of 1991. Colorectal Minimally Invasive Surgery is
      widely implemented and has changed the way we treat our patients, specially due
      to the short-term advantages such as lower morbidity with a better quality of
      life with the same oncological outcomes in the long term. A huge number of
      Spanish surgeons have contributed to the implementation of techniques and
      spreading the knowledge of these concepts by means of courses, controlled
      randomized studies, scientific papers, and books, and have obtained international
      recognition. 

PMID- 26314548
TI  - Activity-based profiling of the proteasome pathway during hepatitis C virus
      infection.
AB  - Hepatitis C virus (HCV) infection often leads to chronic hepatitis, liver
      cirrhosis, and hepatocellular carcinoma. The stability of the HCV proteins is
      controlled by ubiquitin-dependent and ubiquitin-independent proteasome pathways.
      Many viruses modulate proteasome function for their propagation. To examine the
      interrelationship between HCV and the proteasome pathways we employed a
      quantitative activity-based protein profiling method. Using this approach we were
      able to quantify the changes in the activity of several proteasome subunits and
      found that proteasome activity is drastically reduced by HCV replication. The
      results imply a link between the direct downregulation of the activity of this
      pathway and chronic HCV infection. 

PMID- 26314550
TI  - The role of sex, attachment and autonomy-connectedness in personality
      functioning.
AB  - Previous studies have found significant relationships among sex, attachment and
      autonomy-connectedness and DSM-IV personality characteristics. In the present
      study, we aimed to add to the current knowledge about attachment-related aspects
      of personality pathology, by examining the relationships of these same variables
      with dimensions of pathological personality structure as conceptualized by
      Kernberg. The study was performed among 106 ambulatory patients from a Dutch
      mental healthcare institute. A path model based upon neo-analytical object
      relation theory and attachment theory was tested. We expected significant
      associations among sex, attachment, autonomy and aspects of personality
      functioning. Both insecure attachment styles as well as the autonomy
      connectedness components of sensitivity to others (SO) and capacity of managing
      new situations predicted general personality dysfunctioning significantly. More
      specifically, reality testing was negatively predicted by the autonomy component
      of capacity of managing new situations, and aggression was significantly
      predicted by sex as well as both insecure attachment styles. We advise scientists
      as well as clinicians to be alert on sex differences in autonomy-connectedness
      and aspects of personality dysfunctioning. Taking sex-specific variations in
      attachment and autonomy into account next to a more explicit focus on insecure
      attachment styles and autonomy problems may enhance, the current relatively low,
      treatment effectiveness for personality pathology.

PMID- 26314549
TI  - An integrated genome-wide approach to discover deregulated microRNAs in non-small
      cell lung cancer: Clinical significance of miR-23b-3p deregulation.
AB  - In spite of significant technical advances, genesis and progression of non-small
      cell lung cancer (NSCLC) remain poorly understood. We undertook an integrated
      genetic approach to discover novel microRNAs that were deregulated in NSCLCs. A
      total 119 primary NSCLCs with matched normal were analyzed for genome-wide copy
      number changes. We also tested a subset of matched samples by microRNA expression
      array, and integrated them to identify microRNAs positioned in allelic imbalance
      area. Our findings support that most of the identified deregulated microRNAs (miR
      21, miR-23b, miR-31, miR-126, miR-150, and miR-205) were positioned in allelic
      imbalance areas. Among microRNAs tested in independent 114 NSCLCs, overexpression
      of miR-23b was revealed to be a significantly poor prognostic factor of
      recurrence free survival (HR = 2.40, P = 0.005, 95%CI: 1.32-4.29) and overall
      survival (HR = 2.35, P = 0.005, 95%CI: 1.30-4.19) in multivariable analysis. In
      addition, overexpression of miR-23b in H1838 cell line significantly increased
      cell proliferation, while inhibition of miR-23b in H1437 and H1944 cell lines
      significantly decreased cell doubling time. In summary, integration of genomic
      analysis and microRNA expression profiling could identify novel cancer-related
      microRNAs, and miR-23b could be a potential prognostic marker for early stage
      NSCLCs. Further biological studies of miR-23b are warranted for the potential
      development of targeted therapy. 

PMID- 26314551
TI  - The distribution of BRAF gene fusions in solid tumors and response to targeted
      therapy.
AB  - Although the BRAF V600E base substitution is an approved target for the BRAF
      inhibitors in melanoma, BRAF gene fusions have not been investigated as
      anticancer drug targets. In our study, a wide variety of tumors underwent
      comprehensive genomic profiling for hundreds of known cancer genes using the
      FoundationOneTM or FoundationOne HemeTM comprehensive genomic profiling assays.
      BRAF fusions involving the intact in-frame BRAF kinase domain were observed in 55
      (0.3%) of 20,573 tumors, across 12 distinct tumor types, including 20 novel BRAF
      fusions. These comprised 29 unique 5' fusion partners, of which 31% (9) were
      known and 69% (20) were novel. BRAF fusions included 3% (14/531) of melanomas; 2%
      (15/701) of gliomas; 1.0% (3/294) of thyroid cancers; 0.3% (3/1,062) pancreatic
      carcinomas; 0.2% (8/4,013) nonsmall-cell lung cancers and 0.2% (4/2,154) of
      colorectal cancers, and were enriched in pilocytic (30%) vs. nonpilocytic gliomas
      (1%; p < 0.0001), Spitzoid (75%) vs. nonSpitzoid melanomas (1%; p = 0.0001),
      acinar (67%) vs. nonacinar pancreatic cancers (<1%; p < 0.0001) and papillary
      (3%) vs. nonpapillary thyroid cancers (0%; p < 0.03). Clinical responses to
      trametinib and sorafenib are presented. In conclusion, BRAF fusions are rare
      driver alterations in a wide variety of malignant neoplasms, but enriched in
      Spitzoid melanoma, pilocytic astrocytomas, pancreatic acinar and papillary
      thyroid cancers.

PMID- 26314553
TI  - Tenth International Congress of the Eamhid Florence, September 9-11 2015.
      Integrating Different Approaches in the Neurodevelopmental Perspective.

PMID- 26314552
TI  - Efficacy of Medications Approved for the Treatment of Alcohol Dependence and
      Alcohol Withdrawal Syndrome in Female Patients: A Descriptive Review.
AB  - The aim of this study was to evaluate whether the number of women recruited for
      studies to establish the efficacy of medications approved for treatment of
      alcohol dependence (AD) and of alcohol withdrawal syndrome (AWS) is sufficient to
      reveal possible gender differences in the response to these medications and in
      suggesting the use of different doses in female patients. Our results show that
      the rates of women recruited for studies evaluating the efficacy of disulfiram
      (1%), benzodiazepines (3%), and anticonvulsants (13%) were too low to establish
      possible gender differences. The rates of women recruited for studies evaluating
      the efficacy of acamprosate (22%), naltrexone (23%), and nalmefene (30%) were
      higher and allowed evaluation of data obtained for female patients. Women receive
      medications for treatment of AD and/or AWS for which efficacy has been
      demonstrated in studies in which men were more largely represented. 

PMID- 26314554
TI  - Obituary: Cornelius H. Vanderwolf.
AB  - C.H. Vanderwolf described motor correlates of hippocampal theta oscillations and
      uncovered two broad classes: atropine-sensitive and atropine-resistant rhythm
      with likely different behavioral and cognitive significance.

PMID- 26314555
TI  - Chromosome Polymorphism in Microtus (Alexandromys) mujanensis (Arvicolinae,
      Rodentia).
AB  - The Muya Valley vole (Microtus mujanensis) has a constant diploid chromosome
      number of 2n = 38, but an unstable karyotype with polymorphic chromosome pairs.
      Here, we describe 4 karyotypic variants involving 2 polymorphic chromosome pairs,
      MMUJ8 and MMUJ14, in 6 animals from Buryatia using a combination of GTG-banding
      and chromosome painting with M. agrestis probes. We suggest that the polymorphic
      pairs MMUJ8 and MMUJ14 were formed through pericentric inversions that played a
      major role during karyotype evolution of the species. We also propose that the
      stable diploid number with some ongoing polymorphism in the number of chromosome
      arms indicates that this evolutionarily young endemic species of Russian Far East
      is on the way to karyotype and likely species stabilization. 

PMID- 26314556
TI  - Adverse Effects of Sporadic Dialysis on Body Composition.
AB  - OBJECTIVE: The aim of this study is to analyze the body composition of patients
      receiving emergent dialysis and compare their body cell mass (BCM) and fat-free
      mass (FFM) with those of normal subjects. The care of patients receiving
      sporadic, emergent dialysis treatment is a growing public health concern and the
      magnitude of muscle wasting that occurs in this population is not known. DESIGN
      AND METHODS: We used a cross-sectional design with matching to determine
      differences in total body potassium--an indicator of both BCM and FFM--between
      emergent dialysis patients and healthy normal subjects. We studied 22 subjects
      using a 40K counter that measures BCM and FFM and compared them to controls after
      matching with sex, height and weight. RESULTS: In the matched comparison, BCM and
      FFM were significantly lower in subjects with end-stage renal disease (ESRD).
      Unadjusted BCM was 4.7 kg lower and FFM was 8.8 kg lower for those with ESRD
      compared to those without ESRD (p < 0.001, p < 0.001, respectively). Comparison
      with unmatched controls who underwent 40K analysis also revealed significantly
      lower BCM (4.1 kg) and FFM (7.7 kg) in the ESRD subjects (p = 0.004). After
      adjusting for age, height, weight and gender, BCM and FFM were lower by 4.2 and
      7.8 kg, respectively (p < 0.001). Repeated observations were available for a
      subset of ESRD subjects, and the rate of FFM loss over time was significant, with
      the ESRD subjects demonstrating 2.2 kg per year decline (p = 0.01). CONCLUSION:
      We conclude that among other consequences, muscle wasting indicated by decline in
      BCM and FFM is a significant concern in the growing emergent dialysis population.

PMID- 26314557
TI  - Primary pleural angiosarcoma associated with pneumoconiosis: An autopsy case.
AB  - We report a case of pleural angiosarcoma in an adult male patient confirmed by
      autopsy and possibly associated with pneumoconiosis. The lesion was characterized
      by thickened pleura of both lungs with nodular tumors. Histologically, the tumor
      was composed of spindle-to-polygonal epithelioid cells that were positive for
      CD31, CD34, vimentin, and cytokeratin on immunohistochemical staining but were
      negative for calretinin. Further examination revealed mix-dust pathological
      findings consistent with the existence of pneumoconiosis; dystrophic
      ossification, anthracosis, and fractal small dust particles were observed in the
      lung parenchyma and a hilar lymph node. The current case suggests that
      pneumoconiosis-associated pathologies may be risk factors for the development of
      angiosarcoma in the pleura. 

PMID- 26314558
TI  - Plasma levels of growth-related oncogene (CXCL1-3) associated with fibrosis and
      platelet counts in HCV-infected patients.
AB  - BACKGROUND: Fibrosis progression in hepatitis C virus (HCV)-infected patients
      varies greatly between individuals. Chemokines recruit immune cells to the
      infected liver and may thus play a role in the fibrosis process. AIM: To
      investigate plasma levels of a diverse chemokine panel in relation to liver
      fibrosis. METHODS: African-American and Caucasian HCV genotype 1 infected
      patients were treated with peginterferon (pegIFN) and ribavirin (RBV) for 48
      weeks (VIRAHEP-C cohort). Plasma levels of 13 cytokines were studied at baseline
      (n = 386). Subsequently, GROalpha levels were assessed in a sub cohort (n = 99)
      at baseline, and at 4 and 12 weeks after start of pegIFN/RBV treatment. RESULTS:
      Increased severity of fibrosis (Ishak fibrosis score 0-2 vs. 3-6) was associated
      with increased plasma IP-10 (CXCL10) and IL-8 (CXCL8) levels, and decreased
      plasma levels of the chemokine growth-related oncogene (GRO, CXCL1-3). Plasma GRO
      levels were also positively correlated with platelet counts, and were higher in
      African-American as compared to Caucasian patients. In response to pegIFN/RBV
      treatment, GROalpha levels increased in Caucasian but not African-American
      patients from week 4 onwards. CONCLUSIONS: The association with severity of
      fibrosis and platelet count positions plasma GRO as a potential biomarker for
      liver fibrosis in HCV-infected patients. The secretion of GRO by platelets may
      explain the correlation between GRO plasma level and platelet count. The ethnic
      difference in GRO levels both pre-treatment and in response to pegIFN/RBV might
      be driven by a genetic polymorphism in GROalpha associated with higher plasma
      levels and more common in the African-American population.

PMID- 26314560
TI  - Constitutive role of GADD34 and CReP in cancellation of phospho-eIF2alpha
      dependent translational attenuation and insulin biosynthesis in pancreatic beta
      cells.
AB  - Insulin biosynthesis has been well characterized with respect to transcriptional
      and post-translational regulation. However, the relationship between
      translational regulation of insulin and protein quality control in the
      endoplasmic reticulum (ER) remains to be clarified. Here we carried out forced
      expression of insulin in non-insulin-producing cells and compared activation
      level of ER stress-responsive molecules between insulin-producing cells and non
      insulin-producing cells under normal culture condition or ER stress condition.
      Forced expression of insulin in non-insulin-producing cells caused severe ER
      stress with striking translational attenuation through phosphorylation of
      eIF2alpha by activation of protein kinase RNA-like endoplasmic reticulum kinase
      (PERK), resulting in inhibition of insulin production at the protein level. We
      also found that GADD34 and CReP are highly expressed in the cells that
      endogenously produce insulin and that eIF2alpha shows constitutively low
      phosphorylation level in these cells although PERK is constitutively activated
      under both normal culture conditions and physiological conditions in the same
      cells. Inhibition of eIF2alpha phosphatase further decreased insulin level in
      pancreatic beta cells. These findings suggest that eIF2alpha phosphorylation
      level is kept low by GADD34- and/or CReP-regulated phosphatases in pancreatic
      beta cells and that cancellation of phospho-eIF2alpha-dependent translational
      inhibition by the molecular mechanism contributes to mass production of insulin
      in pancreatic beta cells. 

PMID- 26314559
TI  - Association of Light-Intensity Physical Activity With Lower Cardiovascular
      Disease Risk Burden in Rheumatoid Arthritis.
AB  - OBJECTIVE: To characterize physical activity (PA) in individuals with rheumatoid
      arthritis (RA) and to determine the associations between PA participation at
      light to moderate intensities and cardiovascular disease risk factors,
      disability, and disease activity. METHODS: The cross-sectional study used data
      from 2 RA cohorts. PA was measured using an accelerometry-based activity monitor,
      recording minutes/day spent in sedentary (<=1 metabolic equivalent [MET]), very
      light (1.1-1.9 METs), light (2-2.9 METs), and moderate activities (>=3 METs).
      Cardiovascular markers included body mass index, blood pressure, insulin
      resistance, and lipid profile. Disability and disease activity were measured
      using the Health Assessment Questionnaire (HAQ) and the Disease Activity Score in
      28 joints (DAS28), respectively. Associations between PA at each intensity level
      and health markers were assessed by multiple linear regression models, adjusted
      for age, sex, and cohort. RESULTS: Ninety-eight subjects (mean +/- SD age 58 +/-
      9 years, 85% female) were included. Subjects spent 9.8 hours/day being sedentary,
      3.5 hours/day engaged in very light PA, 2.1 hours/day engaged in light PA, and 35
      minutes/day engaged in moderate PA. Only 17% were physically active (>=150
      minutes/week of moderate PA in 10-minute bouts). Regression models showed that
      very light, light, and moderate PA were inversely associated with most
      cardiovascular disease risk factors and HAQ and DAS28 scores (R(2) Delta range
      0.04-0.52, P < 0.05). The associations between PA and cardiovascular disease
      markers were either equivalent or stronger at very light and light intensities,
      as compared to moderate intensity. CONCLUSION: Individuals with RA are mostly
      active at very light and light intensities. PA at these intensity levels
      associates favorably with cardiovascular markers and lower disability and disease
      activity in RA.

PMID- 26314561
TI  - The influence of body mass index on clinical short-term outcomes in robotic
      colorectal surgery.
AB  - BACKGROUND: Robotic surgery has been developed to address the technical
      limitations of laparoscopic surgery and might result in similar outcomes for
      patients with low and high body mass index (BMI). METHODS: Demographic, peri
      operative data and surrogate oncologic markers for colorectal cancer of patients
      that underwent robotic colorectal procedures were collected in a prospective
      database and analyzed. RESULTS: 103 consecutive patients (36 normal-weight, 33
      overweight, 34 obese) underwent robotic colorectal surgery from 11/2011 to
      05/2012. While operating room (OR) time was longer for the obese patients (123.4
      vs 137.9 and 154.7 min), results for estimated blood loss (104.2 vs 153 and 155.9
      mL), conversions (2.8 vs 6.1 and 5.9%), complications (19.4 vs 21.2 and 32.4%),
      re-admissions (11.1 vs 112.1 and 20.6) and mortality (0% for all) were
      comparable. BMI did not affect the surrogate markers in patients with
      malignancies. CONCLUSIONS: Data demonstrates that patient BMI does not have a
      significant impact on short-term clinical outcomes during robotic colorectal
      surgery. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 26314562
TI  - ENVIRONMENTAL EFFECTS ON SUPEROXIDE DISMUTASE AND CATALASE ACTIVITY AND
      EXPRESSION IN HONEY BEE.
AB  - Understanding the cellular stress response in honey bees will significantly
      contribute to their conservation. The aim of this study was to analyze the
      response of the antioxidative enzymes superoxide dismutase and catalase in honey
      bees related to the presence of toxic metals in different habitats. Three
      locations were selected: (i) Tunovo on the mountain Golija, as control area,
      without industry and large human impact, (ii) Belgrade as urban area, and (iii)
      Zajaca, as mining and industrial zone. Our results showed that the concentrations
      of lead (Pb) in whole body of bees vary according to habitat, but there was very
      significant increase of Pb in bees from investigated industrial area. Bees from
      urban and industrial area had increased expression of both Sod1 and Cat genes,
      suggesting adaptation to increased oxidative stress. However, in spite increased
      gene expression, the enzyme activity of catalase was lower in bees from
      industrial area suggesting inhibitory effect of Pb on catalase. 

PMID- 26314563
TI  - Fluorine-Free Anti-Smudge Polyurethane Coatings.
AB  - Conventionally, low-surface-tension fluorinated reagents are incorporated into
      anti-smudge (oil- and water-repellent) coatings for oil repellency. However,
      fluorinated compounds are expensive and an environmental concern because of their
      high stability and bioaccumulation. These factors limit their widespread
      application. We report herein the development of fluorine-free anti-smudge
      polyurethane coatings that are clear at thicknesses up to tens of micrometers and
      are able to sustain extensive surface damage. We demonstrate that these coatings
      can be applied readily onto a diverse range of substrates. 

PMID- 26314564
TI  - Evidence of a role for S. cerevisiae alpha-arrestin Art1 (Ldb19) in mating
      projection and zygote formations.
AB  - The discovery of arrestin-mediated biased signalling mechanisms for mammalian G
      protein coupled receptors (GPCRs) has revolutionized the field over the last
      decade. Now, with the recent demonstration of a role for alpha-arrestins in
      internalization of the yeast pheromone GPCR, Ste2p, the possibility of arrestin
      mediated alternate GPCR functionalities in yeast also follows. Here, the effects
      of knockout and complementation of yeast alpha-arrestin expression during mating
      are reported. Although minor effects on classical pheromone-related signalling
      are noted for a few arrestins, much stronger effects were observed downstream of
      cell cycle arrest, in particular linking Ldb19 (Art1) to mediation of zygote
      formation. Subsequent phenotypic observations linked this activity to more
      pronounced projection formation in an Art1 complemented noncuple alpha-arrestin
      knockout line, compared to the knockout-line alone, or either of the Art3 or Art6
      complemented lines. Together with the observation of ligand-stimulated
      localization of Art-GFP to the mating projection, a possible role for this
      arrestin-like protein in projection formation is supported. While leaving the
      full mechanism of alternate Art1 functionality to be elucidated, together these
      findings implicate Art1 in selective regulation of mating events downstream of
      receptor internalization and cell cycle arrest, leading to schmoo, and ultimately
      zygote formation.

PMID- 26314565
TI  - Phenotypic, Functional, and Gene Expression Profiling of Peripheral CD45RA+ and
      CD45RO+ CD4+CD25+CD127(low) Treg Cells in Patients With Chronic Rheumatoid
      Arthritis.
AB  - OBJECTIVE: Conflicting evidence exists regarding the suppressive capacity of Treg
      cells in the peripheral blood (PB) of patients with rheumatoid arthritis (RA).
      The aim of this study was to determine whether Treg cells are intrinsically
      defective in RA. METHODS: Using a range of assays on PB samples from patients
      with chronic RA and healthy controls, CD3+CD4+CD25+CD127(low) Treg cells from the
      CD45RO+ or CD45RA+ T cell compartments were analyzed for phenotype, cytokine
      expression (ex vivo and after in vitro stimulation), suppression of Teff cell
      proliferation and cytokine production, suppression of monocyte-derived
      cytokine/chemokine production, and gene expression profiles. RESULTS: No
      differences between RA patients and healthy controls were observed with regard to
      the frequency of Treg cells, ex vivo phenotype (CD4, CD25, CD127, CD39, or
      CD161), or proinflammatory cytokine profile (interleukin-17 [IL-17], interferon
      gamma [IFNgamma], or tumor necrosis factor [TNF]). FoxP3 expression was slightly
      increased in Treg cells from RA patients. The ability of Treg cells to suppress
      the proliferation of T cells or the production of cytokines (IFNgamma or TNF)
      upon coculture with autologous CD45RO+ Teff cells and monocytes was not
      significantly different between RA patients and healthy controls. In PB samples
      from some RA patients, CD45RO+ Treg cells showed an impaired ability to suppress
      the production of certain cytokines/chemokines (IL-1beta, IL-1 receptor
      antagonist, IL-7, CCL3, or CCL4) by autologous lipopolysaccharide-activated
      monocytes. However, this was not observed in all patients, and other
      cytokines/chemokines (TNF, IL-6, IL-8, IL-12, IL-15, or CCL5) were generally
      suppressed. Finally, gene expression profiling of CD45RA+ or CD45RO+ Treg cells
      from the PB revealed no statistically significant differences between RA patients
      and healthy controls. CONCLUSION: Our findings indicate that there is no global
      defect in either CD45RO+ or CD45RA+ Treg cells in the PB of patients with chronic
      RA.

PMID- 26314566
TI  - High prevalence of elevated blood pressure among children with neurofibromatosis
      type 1.
AB  - BACKGROUND: Neurofibromatosis type 1 (NF1) is a common neurocutaneous disease
      characterized by cafe-au-lait spots, axillary and inguinal freckling,
      neurofibromas, and optic gliomas. Increased rates of hypertension (HTN) were
      reported among NF1 patients, however, the prevalence of HTN and pre-HTN in
      pediatric NF1 patients has not been clarified. METHODS: Blood pressure (BP)
      measurements, weight, and renal ultrasound were assessed in 224 NF1 pediatric
      patients followed in a specialized NF1 clinic. RESULTS: The cohort's mean age was
      9.1 +/- 4.1 years. Overweight and obesity were found in 12.9 and 10.3 % of them,
      respectively. BP was measured averagely 2.9 times per patient on different
      occasions. Blood pressure was in the pre-HTN and HTN ranges in 14.9 and 16.9 % of
      measurements, respectively. BP >95th was detected in 20.5 % at the first
      measurement. Of 114 children with at least three BP measurements, 18.4 % had two
      values in the HTN range and 6.14 % had at least three. Overweight was not
      associated with HTN among children with NF1. Urinary tract ultrasonographic
      abnormalities were detected in 6.8 % (11/161) of cases. CONCLUSIONS: The
      prevalence of increased BP in pediatric NF1 is much higher than in the general
      pediatric population. BP has to be regularly assessed and managed in this high
      risk population.

PMID- 26314567
TI  - Patient acceptability, efficacy, and skin biophysiology of a cream and cleanser
      containing lipid complex with shea butter extract versus a ceramide product for
      eczema.
AB  - OBJECTIVES: To investigate patient acceptability, efficacy, and skin
      biophysiological effects of a cream/cleanser combination for childhood atopic
      dermatitis. SETTING: Paediatric dermatology clinic at a university teaching
      hospital in Hong Kong. PATIENTS: Consecutive paediatric patients with atopic
      dermatitis who were interested in trying a new moisturiser were recruited between
      1 April 2013 and 31 March 2014. Swabs and cultures from the right antecubital
      fossa and the worst eczematous area, disease severity (SCORing Atopic Dermatitis
      index), skin hydration, and transepidermal water loss were obtained prior to and
      following 4-week usage of a cream/cleanser containing lipid complex with shea
      butter extract (Ezerra cream; Hoe Pharma, Petaling Jaya, Malaysia). Global or
      general acceptability of treatment was documented as 'very good', 'good', 'fair',
      or 'poor'. RESULTS: A total of 34 patients with atopic dermatitis were recruited;
      74% reported 'very good' or 'good', whereas 26% reported 'fair' or 'poor' general
      acceptability of treatment of the Ezerra cream; and 76% reported 'very good' or
      'good', whereas 24% reported 'fair' or 'poor' general acceptability of treatment
      of the Ezerra cleanser. There were no intergroup differences in pre-usage
      clinical parameters of age, objective SCORing Atopic Dermatitis index, pruritus,
      sleep loss, skin hydration, transepidermal water loss, topical corticosteroid
      usage, oral antihistamine usage, or general acceptability of treatment of the
      prior emollient. Following use of the Ezerra cream, mean pruritus score decreased
      from 6.7 to 6.0 (P=0.036) and mean Children's Dermatology Life Quality Index
      improved from 10.0 to 8.0 (P=0.021) in the 'very good'/'good' group. There were
      no statistically significant differences in the acceptability of wash (P=0.526)
      and emollients (P=0.537) with pre-trial products. When compared with the data of
      another ceramide-precursor moisturiser in a previous study, there was no
      statistical difference in efficacy and acceptability between the two products.
      CONCLUSIONS: The trial cream was acceptable in three quarters of patients with
      atopic dermatitis. Patients who accepted the cream had less pruritus and improved
      quality of life than the non-accepting patients following its usage. The cream
      containing shea butter extract did not differ in acceptability or efficacy from a
      ceramide-precursor product. Patient acceptability is an important factor for
      treatment efficacy. There is a general lack of published clinical trials to
      document the efficacy and skin biophysiological effects of many of the
      proprietary moisturisers.

PMID- 26314568
TI  - Corticosteroid adulteration in proprietary Chinese medicines: a recurring
      problem.
AB  - OBJECTIVES: To investigate adulteration of proprietary Chinese medicines with
      corticosteroids in Hong Kong. DESIGN: Case series with cross-sectional analysis.
      SETTING: A tertiary clinical toxicology laboratory in Hong Kong. PATIENTS: All
      patients using proprietary Chinese medicines adulterated with corticosteroids and
      referred to the authors' centre from 1 January 2008 to 31 December 2012. MAIN
      OUTCOME MEASURES: Patients' demographic data, clinical presentation, medical
      history, drug history, laboratory investigations, and analytical findings of the
      proprietary Chinese medicines were analysed. RESULTS: The records of 61 patients
      who consumed corticosteroid-adulterated proprietary Chinese medicines were
      reviewed. The most common corticosteroid implicated was dexamethasone. Co
      adulterants such as non-steroidal anti-inflammatory drugs and histamine H1
      receptor antagonists were detected in the proprietary Chinese medicine specimens.
      Among the patients, seven (11.5%) required intensive care, two (3.3%) died within
      30 days of presentation, and 38 (62.3%) had one or more complications that were
      potentially attributable to exogenous corticosteroids. Of 22 (36.1%) patients who
      had provocative adrenal function testing performed, 17 (77.3% of those tested)
      had adrenal insufficiency. CONCLUSION: The present case series is the largest
      series of patients taking proprietary Chinese medicines adulterated with
      corticosteroids. Patients taking these illicit products are at risk of severe
      adverse effects, including potentially fatal complications. Adrenal insufficiency
      was very common in this series of patients. Assessment of adrenal function in
      these patients, however, has been inadequate and routine rather than
      discretionary testing of adrenal function is indicated in this group of patients.
      The continuing emergence of proprietary Chinese medicines adulterated with
      western medication indicates a persistent threat to public health.

PMID- 26314569
TI  - Using the script concordance test to assess clinical reasoning skills in
      undergraduate and postgraduate medicine.
AB  - The script concordance test is a relatively new format of written assessment that
      is used to assess higher-order clinical reasoning and data interpretation skills
      in medicine. Candidates are presented with a clinical scenario, followed by the
      reveal of a new piece of information. The candidates are then asked to assess
      whether this additional information increases or decreases the probability or
      likelihood of a particular diagnostic, investigative, or management decision. To
      score these questions, the candidate's decision in each question is compared with
      that of a reference panel of expert clinicians. This review focuses on the
      development of quality script concordance questions, using expert panellists to
      score the items and set the passing score standard, and the challenges in the
      practical implementation (including pitfalls to avoid) of the written assessment.

PMID- 26314570
TI  - Teasaponin improves leptin sensitivity in the prefrontal cortex of obese mice.
AB  - SCOPE: Obesity impairs cognition, and the leptin-induced increase of brain
      derived neurotrophic factor (BDNF) and neurogenesis. Tea consumption improves
      cognition and increases brain activation in the prefrontal cortex. METHODS AND
      RESULTS: This study examined whether teasaponin, an active ingredient in tea,
      could improve memory and central leptin effects on neurogenesis in the prefrontal
      cortex of obese mice, and in vitro in cultured prefrontal cortical neurons.
      Teasaponin (10 mg/kg, intraperitoneal) for 21 days improved downstream leptin
      signaling (JAK2 and STAT3), and leptin's effect on BDNF, in the prefrontal cortex
      of high-fat diet (HFD) fed mice. Prefrontal cortical neurons were cultured with
      teasaponin and palmitic acid (the most abundant dietary saturated fatty acid) to
      examine their effects on neurogenesis and BDNF expression in response to leptin.
      Palmitic acid decreased leptin's effect on neurite outgrowth, postsynaptic
      density protein 95, and BDNF expression in cultured cortical neurons, which was
      reversed by teasaponin. CONCLUSION: Teasaponin improved the leptin sensitivity of
      prefrontal cortical neurons in obese mice or when treated by palmitic acid. This
      in turn increased BDNF expression and neurite growth. Therefore, teasaponin
      supplementation may be used to prevent obesity-associated neurodegeneration and
      improve cognitive function.

PMID- 26314572
TI  - Erratum to: In Memoriam...George J. Hill, M.D., Ph.D.

PMID- 26314571
TI  - Messages of Hope: Helping Family Members to Overcome Fears and Fatalistic
      Attitudes Toward Cancer.
AB  - This qualitative study explored strategies family members of African-American
      cancer patients used to overcome their fears and fatalistic attitudes toward
      cancer. Twenty-four family members were recruited through criterion purposeful
      sampling. Data were collected and analyzed using open-ended interviews and
      thematic analysis. Fears and fatalistic attitudes could be traced to personal
      experiences with cancer and information being communicated within their networks.
      Strategies used to overcome fears and fatalistic attitudes toward cancer included
      an awareness of advances in cancer treatments, information obtained from their
      health-care providers, and faith in God. Family members supported the patient
      through efforts of encouraging them to talk about what they were going through,
      to be strong, to maintain a positive environment and normalcy, and to use
      spirituality as a source of strength. Family members also suggested that health
      care providers and researchers tailor intervention studies to consider that the
      patient is a part of a larger family system and that the entire family needs
      support to overcome long-held fears and fatalistic attitudes toward cancer. These
      findings suggest that despite advances in cancer care and widespread media
      coverage to change perceptions about cancer, fears and fatalistic attitudes
      toward cancer persist and likely influence the family members' ability to
      optimally support the cancer patient. At the time of diagnosis, both patient and
      the entire family unit should be educated of advances in cancer care, that cancer
      is no longer a death sentence, and supported to overcome fears and fatalistic
      attitudes.

PMID- 26314573
TI  - Rights of Cancer Patient's: a Pilot Study from Turkey.
AB  - The chief aims of this study are to examine the levels of knowledge of cancer
      patients who have been receiving treatment in Turkey, related to the patient's
      rights they have, and determine the personal factors that affect their level of
      knowledge. The research was conducted with 294 patients who have been receiving
      treatment in a university hospital in Ankara. Findings have manifested that
      although the patients had some level of knowledge about fundamental rights of the
      patients, they have never used a great deal of them and they had no knowledge of
      plenty of important patient's rights. It is concluded that in order for cancer
      patients to participate in the treatment they receive, their level knowledge of
      patient's rights should be enhanced and this should be provided by education.

PMID- 26314574
TI  - Atomoxetine pharmacogenetics: associations with pharmacokinetics, treatment
      response and tolerability.
AB  - Atomoxetine is indicated for the treatment of attention deficit hyperactivity
      disorder and is predominantly metabolized by the CYP2D6 enzyme. Differences in
      pharmacokinetic parameters as well as clinical treatment outcomes across CYP2D6
      genotype groups have resulted in dosing recommendations within the product label,
      but clinical studies supporting the use of genotype guided dosing are currently
      lacking. Furthermore, pharmacokinetic and clinical studies have primarily focused
      on extensive as compared with poor metabolizers, with little information known
      about other metabolizer categories as well as genes involved in the
      pharmacodynamics of atomoxetine. This review describes the pharmacogenetic
      associations with atomoxetine pharmacokinetics, treatment response and
      tolerability with considerations for the clinical utility of this information. 

PMID- 26314575
TI  - Praziquantel treatment for yellowtail kingfish (Seriola lalandi): dose and
      duration safety study.
AB  - Regulatory approval is being sought to use praziquantel (PZQ) to treat flukes
      infecting yellowtail kingfish (YTK), but accurate safety data were not available.
      We investigated the effect of increased doses or prolonged exposure of orally
      administered PZQ on YTK by assessing changes in haematological and biochemical
      characteristics, and mortality. Fish were intubated daily for 3 days with 0, 100,
      300 and 500 mg PZQ kg(-1) BW day(-1) or once daily for 9 days at 0 and 100 mg PZQ
      kg(-1) BW day(-1). Blood was taken 24 h after the cessation of treatment. There
      was no significant difference between any of the haematological or biochemical
      indices in YTK treated with PZQ and controls, indicating that PZQ is safe for use
      at 100 mg PZQ kg(-1) BW day(-1) in YTK and that exposure to high doses or
      prolonged duration does not have negative effects on the YTK haematological or
      biochemical parameters we measured.

PMID- 26314576
TI  - A Model of Isotope Separation in Cells at the Early Stages of Evolution.
AB  - The separation of the isotopes of certain ions can serve as an important
      criterion for the presence of life in the early stages of its evolution. A model
      of the separation of isotopes during their transport through the cell membrane is
      constructed. The dependence of the selection coefficient on various parameters is
      found. In particular, it is shown that the maximum efficiency of the transport of
      ions corresponds to the minimum enrichment coefficient. At the maximum
      enrichment, the efficiency of the transport system approaches 1/2. Calculated
      enrichment coefficients are compared with experimentally obtained values for
      different types of cells, and the comparison shows a qualitative agreement
      between these quantities. 

PMID- 26314578
TI  - MGFM: a novel tool for detection of tissue and cell specific marker genes from
      microarray gene expression data.
AB  - BACKGROUND: Identification of marker genes associated with a specific tissue/cell
      type is a fundamental challenge in genetic and cell research. Marker genes are of
      great importance for determining cell identity, and for understanding tissue
      specific gene function and the molecular mechanisms underlying complex diseases.
      RESULTS: We have developed a new bioinformatics tool called MGFM (Marker Gene
      Finder in Microarray data) to predict marker genes from microarray gene
      expression data. Marker genes are identified through the grouping of samples of
      the same type with similar marker gene expression levels. We verified our
      approach using two microarray data sets from the NCBI's Gene Expression Omnibus
      public repository encompassing samples for similar sets of five human tissues
      (brain, heart, kidney, liver, and lung). Comparison with another tool for tissue
      specific gene identification and validation with literature-derived established
      tissue markers established functionality, accuracy and simplicity of our tool.
      Furthermore, top ranked marker genes were experimentally validated by reverse
      transcriptase-polymerase chain reaction (RT-PCR). The sets of predicted marker
      genes associated with the five selected tissues comprised well-known genes of
      particular importance in these tissues. The tool is freely available from the
      Bioconductor web site, and it is also provided as an online application
      integrated into the CellFinder platform ( http://cellfinder.org/analysis/marker
      ). CONCLUSIONS: MGFM is a useful tool to predict tissue/cell type marker genes
      using microarray gene expression data. The implementation of the tool as an R
      package as well as an application within CellFinder facilitates its use.

PMID- 26314577
TI  - Multidimensional individualised Physical ACTivity (Mi-PACT)--a technology-enabled
      intervention to promote physical activity in primary care: study protocol for a
      randomised controlled trial.
AB  - BACKGROUND: Low physical activity is a major public health problem. New cost
      effective approaches that stimulate meaningful long-term changes in physical
      activity are required, especially within primary care settings. It is becoming
      clear that there are various dimensions to physical activity with independent
      health benefits. Advances in technology mean that it is now possible to generate
      multidimensional physical activity 'profiles' that provide a more complete
      representation of physical activity and offer a variety of options that can be
      tailored to the individual. Mi-PACT is a randomised controlled trial designed to
      examine whether personalised multidimensional physical activity feedback and self
      monitoring alongside trainer-supportive sessions increases physical activity and
      improves health outcomes in at-risk men and women. METHODS/DESIGN: We aim to
      recruit 216 patients from within primary care aged 40 to 70 years and at medium
      or high risk of cardiovascular disease and/or type II diabetes mellitus. Adopting
      an unequal allocation ratio (intervention: control) of 2:1, participants will be
      randomised to one of two groups, usual care or the intervention. The control
      group will receive usual care from their general practitioner (GP) and
      standardised messages about physical activity for health. The intervention group
      will receive physical activity monitors and access to a web-based platform for a
      3-month period to enable self-monitoring and the provision of personalised
      feedback regarding the multidimensional nature of physical activity. In addition,
      this technology-enabled feedback will be discussed with participants on 5
      occasions during supportive one-to-one coaching sessions across the 3-month
      intervention. The primary outcome measure is physical activity, which will be
      directly assessed using activity monitors for a 7-day period at baseline, post
      intervention and at 12 months. Secondary measures (at these time-points) include
      weight loss, fat mass, and markers of metabolic control, motivation and well
      being. DISCUSSION: Results from this study will provide insight into the effects
      of integrated physical activity profiling and self-monitoring combined with in
      person support on physical activity and health outcomes in patients at risk of
      future chronic disease. TRIAL REGISTRATION: ISRCTN18008011 Trial registration
      date: 31 July 2013.

PMID- 26314579
TI  - Impact of 5A/6A polymorphism of matrix metalloproteinase-3 on recurrent
      atherosclerotic ischemic stroke in Chinese.
AB  - Little is known about the impact of the 5A/6A polymorphism of matrix
      metalloproteinase-3 (MMP-3) on recurrence of atherosclerotic ischemic stroke in
      Chinese. The aim of this study was to investigate the association of MMP-3 serum
      level and 5A/6A genetic polymorphism with the recurrence of atherosclerotic
      ischemic stroke in the Chinese Han population. We analyzed 106 large artery
      atherosclerosis (LAA) recurrent ischemic stroke patients and 545 LAA first onset
      ischemic stroke patients from January 2009 to June 2014. Serum MMP-3
      concentrations were measured with an enzyme-linked immunosorbent assay. The
      genotypes of MMP-3 promoter polymorphism (-1171 5A/6A) were determined using
      polymerase chain reaction-restriction fragment length polymorphism. The
      frequencies of MMP-3 5A/6A+5A/5A (32.08% vs. 21.47%, p = 0.02) genotype and 5A
      (16.98% vs. 11.01%, p = 0.01) allele in the recurrent group was significantly
      higher than those in the first onset group. After adjustment for vascular risk
      factors, multivariate logistic regression analysis suggested that the MMP-3
      5A/6A+5A/5A genotype was an independent risk factor for LAA recurrent ischemic
      stroke (odds ratio [OR], 1.74; 95% confidence interval [CI], 1.09-2.79, p =
      0.021). No significant difference was observed for the MMP-3 serum concentrations
      between the recurrent group and the first onset group (22.23 +/- 8.31 vs. 21.49
      +/- 7.89 ng/ul, t = 0.88, p = 0.38). The MMP-3 (-1171 5A/6A) polymorphism may
      contribute to LAA recurrent ischemic stroke susceptibility. Analysis of 5A/6A
      polymorphism in MMP-3 may identify patients at higher risk for LAA ischemic
      stroke recurrence, who may be selected for intensive preventive therapy. 

PMID- 26314580
TI  - Screening anthelmintic resistance to triclabendazole in Fasciola hepatica
      isolated from sheep by means of an egg hatch assay.
AB  - BACKGROUND: In the present study, the detection of anthelmintic resistance to
      triclabendazole (TCBZ) in sheep infected by Fasciola hepatica was studied using
      an egg hatch assay (EHA). F. hepatica eggs were recovered from bile and faeces of
      infected animals by isolates with different grade of anthelmintic resistance to
      TCBZ: i) a resistant isolate (RT); ii) a susceptible isolate (ST); iii) naturally
      infected sheep by a susceptible field strain (FST). In the EHA the percentage of
      hatched eggs were calculated according to the following concentrations of TCBZ
      diluted in dimethyl-sulfoxide (DMSO): 0.05, 0.2, 1, 5, and 25 MUg/ml. RESULTS: In
      relation to the EHAs carried out with the eggs from bile of sheep infected by ST,
      differences were found in the percentage of hatched eggs between the control
      well, only with DMSO, and the two highest concentrations of TCBZ (5 and 25 MUg/m)
      (p < 0.05). However, when we tested the drug with the eggs from the bile of sheep
      infected by RT, the percentage of hatched eggs was similar among all
      concentrations. Since the range of hatching varied between isolates, we
      calculated the ratio of the results of each concentration to its control value
      confirming the higher hatching in RT than in ST. We developed an EHA with eggs
      recovered from faeces in order to avoid the slaughter of sheep. The results of
      the EHAs with the isolate ST showed differences in the percentage of hatching
      between the highest concentration (25 MUg/ml) and the control well (p < 0.05);
      however, these differences were not confirmed under field conditions with the
      strain FST. CONCLUSIONS: The ovicidal effect of TCBZ in F. hepatica eggs from
      bile was shown using a commercial formulation diluted in DMSO with a minimum
      concentration of 5 MUg/ml. However, in eggs recovered from faeces the results are
      not conclusive. The cleaning of eggs recovered from faeces is an important issue
      that should be reviewed and standardized before comparing results between
      susceptible and resistant isolates in this kind of EHA.

PMID- 26314581
TI  - Positive family history of colorectal cancer in a general practice setting
      [FRIDA.Frankfurt]: study protocol of a of a cross-sectional study.
AB  - BACKGROUND: Although the risk of developing colorectal cancer (CRC) is 2-4 times
      higher in case of a positive family history, risk-adapted screening programs for
      family members related to CRC- patients do not exist in the German health care
      system. CRC screening recommendations for persons under 55 years of age that have
      a family predisposition have been published in several guidelines. The primary
      aim of this study is to determine the frequency of positive family history of CRC
      (1st degree relatives with CRC) among 40-54 year old persons in a general
      practitioner (GP) setting in Germany. Secondary aims are to detect the frequency
      of occurrence of colorectal neoplasms (CRC and advanced adenomas) in 1st degree
      relatives of CRC patients and to identify the variables (e.g. demographic,
      genetic, epigenetic and proteomic characteristics) that are associated with it.
      This study also explores whether evidence-based information contributes to
      informed decisions and how screening participation correlates with anxiety and
      (anticipated) regret. METHODS/DESIGN: Prior to the beginning of the study, the GP
      team (GP and one health care assistant) in around 50 practices will be trained,
      and about 8,750 persons that are registered with them will be asked to complete
      the "Network against colorectal cancer" questionnaire. The 10% who are expected
      to have a positive family history will then be invited to give their informed
      consent to participate in the study. All individuals with positive family history
      will be provided with evidence-based information and prevention strategies. We
      plan to examine each participant's family history of CRC in detail and to collect
      information on further variables (e.g. demographics) associated with increased
      risk. Additional stool and blood samples will be collected from study
      participants who decide to undergo a colonoscopy (n ~ 350) and then analyzed at
      the German Cancer Research Center (DKFZ) Heidelberg to see whether further
      relevant variables are associated with an increased risk of CRC. One screening
      list and four questionnaires will be used to collect the data, and a detailed
      statistical analysis plan will be provided before the database is closed
      (expected to be June 30, 2015). DISCUSSION: It is anticipated that when persons
      with a family history of colorectal cancer have been provided with professional
      advice by the practice team, there will be an increase in the availability of
      valid information on the frequency of affected individuals and an increase in the
      number of persons making informed decisions. We also expect to identify further
      variables that are associated with colorectal cancer. This study therefore has
      translational relevance from lab to practice. TRIAL REGISTRATION: German Clinical
      Trials Register DRKS00006277.

PMID- 26314583
TI  - Screening for Attenuated Forms of Mucopolysaccharidoses in Patients with
      Osteoarticular Problems of Unknown Etiology.
AB  - INTRODUCTION: The mucopolysaccharidoses (MPS) are a group of 11 inborn errors of
      metabolism (IEM) which are part of the lysosomal storage diseases (LSDs). The MPS
      are multisystemic conditions that affect the entire body, with variations in the
      clinical presentation, having specific treatments available depending on the type
      of MPS. Nearly all MPS disorders compromise the osteoarticular system in
      different ways, and virtually all patients have abnormal urinary excretion of
      glycosaminoglycans (GAGs). MPS are rare diseases that are underdiagnosed due to
      health-care professionals' lack of awareness, to poor access to screening and
      diagnostic methods, and to their extensive clinical heterogeneity. Attenuated
      forms may occur, which can make diagnosis of MPS even more difficult. METHODS:
      This study was conducted prospectively from March 2012 to January 2014 and
      included 55 patients at rheumatology and/or orthopedic services in Porto Alegre,
      Brazil. The screened patients presented with articular manifestations with no
      defined etiology. These patients were screened by quantitative and qualitative
      assessment of urinary GAGs. RESULTS AND DISCUSSION: Among the 55 cases
      investigated, one 15-year-old patient exhibited increased urinary GAG excretion;
      this patient was subsequently diagnosed with an attenuated form of MPS II, which
      was previously undetected. CONCLUSION: Although the proportion of patients with
      MPS identified in the study sample was small (1/55), this study shows that these
      diseases are underdiagnosed and that systematic screening can help identify
      patients who may benefit from specific treatments already available for several
      MPS types.

PMID- 26314582
TI  - Laparoscopic transperitoneal lateral adrenalectomy for malignant and potentially
      malignant adrenal tumours.
AB  - BACKGROUND: Laparoscopic adrenalectomy is still controversial in cases where
      malignancy is suspected. However, many proponents of this technique argue that in
      the hands of an experienced surgeon, laparoscopy can be safely performed. The aim
      of this study is to present our own experience with the application of
      laparoscopic surgery for the treatment of malignant and potentially malignant
      adrenal tumours. METHODS: Our analysis included 52 patients who underwent
      laparoscopic adrenalectomy in 2003-2014 due to a malignant or potentially
      malignant adrenal tumour. Inclusion criteria were primary adrenal malignancy,
      adrenal metastasis or pheochromocytoma with a PASS score greater than 6. We
      analyzed the conversion rate, intra- and postoperative complications,
      intraoperative blood loss and R0 resection rate. Survival was estimated using the
      Kaplan-Meier method. RESULTS: Conversion was necessary in 5 (9.7%) cases.
      Complications occurred in a total of 6 patients (11.5%). R0 resection was
      achieved in 41 (78.8%) patients and R1 resection in 9 (17.3%) patients. In 2
      (3.9%) cases R2 resection was performed. The mean follow-up time was 32.9 months.
      Survival depended on the type of tumour and was comparable with survival after
      open adrenalectomy presented in other studies. CONCLUSIONS: We consider that
      laparoscopic surgery for adrenal malignancy can be an equal alternative to open
      surgery and in the hand of an experienced surgeon it guarantees the possibility
      of noninferiority. Additionally, starting a procedure with laparoscopy allows for
      minimally invasive evaluation of peritoneal cavity. The key element in surgery
      for any malignancy is not the surgical access itself but the proper technique.

PMID- 26314584
TI  - Hyperfractionated stereotactic reirradiation for recurrent head and neck cancer.
AB  - PURPOSE: The goal of this work was to evaluate the efficacy and toxicity of
      hyperfractionated stereotactic reirradiation (re-RT) as a treatment for
      inoperable, recurrent, or second primary head and neck squamous cell cancer
      (HNSCC) that is not suitable for systemic treatment. PATIENTS AND MATERIALS:
      Forty patients with recurrent or second primary HNSCC were included in this
      study. The patients had a median gross tumor volume of 76 ml (range 14-193 ml)
      and a previous radiotherapy dose greater than 60 Gy. Treatment was designed to
      cover 95 % of the planning target volume (PTV, defined as gross tumor volume
      [GTV] + 3 mm to account for microscopic spreading, with no additional set-up
      margin) with the prescribed dose (48 Gy in 16 fractions b.i.d.). Treatment was
      administered twice daily with a minimum 6 h gap. Uninvolved lymph nodes were not
      irradiated. RESULTS: Treatment was completed as planned for all patients (with
      median duration of 11 days, range 9-14 days). Acute toxicity was evaluated using
      the RTOG/EORTC scale. A 37 % incidence of grade 3 mucositis was observed, with
      recovery time of <= 4 weeks for all of these patients. Acute skin toxicity was
      never observed to be higher than grade 2. Late toxicity was also evaluated
      according to the RTOG/EORTC scale. Mandible radionecrosis was seen in 4 cases (10
      %); however, neither carotid blowout syndrome nor other grade 4 late toxicity
      occurred. One-year overall survival (OS) and local progression-free survival (L
      PFS) were found to be 33 and 44 %, respectively. Performance status and GTV
      proved to be significant prognostic factors regarding local control and survival.
      CONCLUSION: Hyperfractionated stereotactic re-RT is a reasonable treatment option
      for patients with recurrent/second primary HNSCC who were previously exposed to
      high-dose irradiation and who are not candidates for systemic treatment or
      hypofractionation.

PMID- 26314585
TI  - Contribution of microRNA analysis to characterisation of pancreatic lesions: a
      review.
AB  - Pancreatic tumours are usually very aggressive cancer with a poor prognosis. A
      limitation of pancreatic imaging techniques is that lesions are often of
      ambiguous relevance. The inability to achieve a definitive diagnosis based on
      cytological evaluation of specimens, due to sampling error, paucicellular samples
      or coexisting inflammation, might lead to delay in clinical management. Given the
      morbidity associated with pancreatectomy, a proper selection of patients for
      surgery is fundamental. Many studies have been conducted in order to identify
      specific markers that could support the early diagnosis of pancreatic lesions,
      but, to date, none of them allow to diagnose pancreatic cancer with high
      sensitivity and specificity. MicroRNAs (miRNA) are small non-coding RNAs (19-25
      nucleotides) that regulate gene expression interacting with mRNA targets. It is
      now established that each tissue shows a characteristic miRNA expression pattern
      that could be modified in association with a number of different diseases
      including neoplasia. Due to their key role in the regulation of gene expression,
      in the last years several studies have investigated miRNA tissue-specific
      expression, quantification and functional analysis to understand their peculiar
      involvement in cellular processes. The aim of this review is to focus on miRNA
      expression in pancreatic cancer and their putative role in early characterisation
      of pancreatic lesions. 

PMID- 26314586
TI  - Patterns of interaction-dominant dynamics in individual versus collaborative
      memory foraging.
AB  - The extent to which a cognitive system's behavioral dynamics fit a power law
      distribution is considered indicative of the extent to which that system's
      behavior is driven by multiplicative, interdependent interactions between its
      components. Here, we investigate the dynamics of memory processes in individual
      and collaborating participants. Collaborative dyads showed the characteristic
      collaborative inhibition effect when compared to nominal groups in terms of the
      number of items retrieved in a categorical recall task, but they also generate
      qualitatively different patterns of search behavior. To categorize search
      behavior, we used multi-model inference to compare the degree to which five
      candidate models (normal, exponential, gamma, lognormal, and Pareto) described
      the temporal distribution of each individual and dyad's recall processes. All
      individual and dyad recall processes were best fit by interaction-dominant
      distributions (lognormal and Pareto), but a clear difference emerged in that
      individual behavior is more power law, and collaborative behavior was more
      lognormal. We discuss these results in terms of the cocktail model (Holden et al.
      in Psychol Rev 116(2):318-342, 2009), which suggests that as a task becomes more
      constrained (such as through the necessity of collaborating), behavior can shift
      from power law to lognormal. This shift may reflect a decrease in the dyad's
      ability to flexibly shift between perseverative and explorative search patterns.
      Finally, our results suggest that a fruitful avenue for future research would be
      to investigate the constraints modulating the shift from power law to lognormal
      behavior in collaborative memory search. 

PMID- 26314587
TI  - Physical activity and exercise training in multiple sclerosis: a review and
      content analysis of qualitative research identifying perceived determinants and
      consequences.
AB  - PURPOSE: This systematic review was conducted to provide rich and deep evidence
      of the perceived determinants and consequences of physical activity and exercise
      based on qualitative research in multiple sclerosis (MS). METHOD: Electronic
      databases and article reference lists were searched to identify qualitative
      studies of physical activity and exercise in MS. Studies were included if they
      were written in English and examined consequences/determinants of physical
      activity in persons with MS. Content analysis of perceived determinants and
      consequences of physical activity and exercise was undertaken using an inductive
      analysis guided by the Physical Activity for people with Disabilities framework
      and Social Cognitive Theory, respectively. RESULTS: Nineteen articles were
      reviewed. The most commonly identified perceived barriers of physical activity
      and exercise were related to the environmental (i.e. minimal or no disabled
      facilities, and minimal or conflicting advice from healthcare professionals) and
      related to personal barriers (i.e. fatigue, and fear and apprehension). The most
      commonly identified perceived facilitators of physical activity were related to
      the environment (i.e. the type of exercise modality and peer support) and related
      to personal facilitators (i.e. appropriate exercise and feelings of
      accomplishment). The most commonly identified perceived beneficial consequences
      of physical activity and exercise were maintaining physical functions, increased
      social participation and feelings of self-management and control. The most
      commonly identified perceived adverse consequences were increased fatigue and
      feelings of frustration and lost control. CONCLUSIONS: Results will inform future
      research on the perceived determinants and consequences of physical activity and
      exercise in those with MS and can be adopted for developing professional
      education and interventions for physical activity and exercise in MS.
      IMPLICATIONS FOR REHABILITATION: Physical activity and exercise behaviour in
      people with multiple sclerosis (MS) is subject to a number of modifiable
      determinants. Healthcare professionals working to promote physical activity and
      exercise in those with MS should choose to endorse the positive benefits of
      participation. Future physical activity interventions for those with MS may be
      improved by incorporating behavioural management strategies.

PMID- 26314588
TI  - Comparison of caloric reactivity between migraineurs and non-migraineurs.
AB  - OBJECTIVE: To demonstrate that the elevated prevalence of migraine in patients
      with vertigo disorders is due to enhanced sensitivity to dizziness, which could
      cause migraineurs to seek more, or earlier, medical care for vertigo disorders,
      confounding the ability to show causation. METHODS: This case-control study
      investigated whether migraineurs perceive dizziness more intensely than non
      migraineurs by comparing caloric responses in migraineurs, non-migraineurs and
      possible migraineurs. The summed caloric responses in the best responding ear
      were reviewed. RESULTS: The migraine group had higher caloric response values,
      with a mean of 37.97 degrees per second, which was statistically significant when
      compared to the values for the possible migraine group (30.74 degrees per second
      (p < 0.05)) and the non-migraine group (30.70 degrees per second (p < 0.001)).
      CONCLUSION: The findings suggest that migraineurs experience vestibular stimuli
      more intensely compared to non-migraineurs, which might explain the association
      of migraine with vestibular disorders in general.

PMID- 26314590
TI  - Mechanisms for SU5416 as a radiosensitizer of endothelial cells.
AB  - Endothelial cells (ECs), that comprise the tumor vasculature, are critical
      targets for anticancer radiotherapy. The aim of this work was to study the
      mechanism by which SU5416, a known anti-angiogenesis inhibitor, modifies the
      radiation responses of human vascular ECs. Two human endothelial cell lines
      (HUVEC and 2H11) were treated with SU5416 alone, radiation alone, or a
      combination of both. In vitro tests were performed using colony forming assays,
      FACS analysis, western blotting, immunohistochemistry, migration assay, invasion
      assays and endothelial tube formation assays. The combination of radiation and
      SU5416 significantly inhibited cell survival, the repair of radiation-induced DNA
      damage, and induced apoptosis. It also caused cell cycle arrest, inhibited cell
      migration and invasion, and suppressed angiogenesis. In this study, our results
      first provide a scientific rationale to combine SU5416 with radiotherapy to
      target ECs and suggest its clinical application in combination cancer treatment
      with radiotherapy.

PMID- 26314591
TI  - Atomic layer deposition of NiO hole-transporting layers for polymer solar cells.
AB  - NiO is an attractive hole-transporting material for polymer solar cells (PSCs)
      owing to its excellent stability and electrical/optical properties. This study
      demonstrates, for the first time, fabrication of uniform, defect-free, and
      conformal NiO ultra-thin films for use as hole-transporting layers (HTLs) in PSCs
      by atomic layer deposition (ALD) through optimization of the ALD processing
      parameters. The morphological, optical, and electrical properties of ALD NiO
      films were determined to be favorable for their HTL application. As a result,
      PSCs containing an ALD NiO HTL with an optimized thickness of 4 nm achieved a
      power conversion efficiency (PCE) of 3.4%, which was comparable to that of a
      control device with a poly(3,4-ethylenedioxy-thiophene):poly(styrene-sulfonate)
      HTL. The high quality and manufacturing scalability of ALD NiO films demonstrated
      here will facilitate the adoption of NiO HTLs in PSCs. 

PMID- 26314589
TI  - A mouse informatics platform for phenotypic and translational discovery.
AB  - The International Mouse Phenotyping Consortium (IMPC) is providing the world's
      first functional catalogue of a mammalian genome by characterising a knockout
      mouse strain for every gene. A robust and highly structured informatics platform
      has been developed to systematically collate, analyse and disseminate the data
      produced by the IMPC. As the first phase of the project, in which 5000 new
      knockout strains are being broadly phenotyped, nears completion, the informatics
      platform is extending and adapting to support the increasing volume and
      complexity of the data produced as well as addressing a large volume of users and
      emerging user groups. An intuitive interface helps researchers explore IMPC data
      by giving overviews and the ability to find and visualise data that support a
      phenotype assertion. Dedicated disease pages allow researchers to find new mouse
      models of human diseases, and novel viewers provide high-resolution images of
      embryonic and adult dysmorphologies. With each monthly release, the informatics
      platform will continue to evolve to support the increased data volume and to
      maintain its position as the primary route of access to IMPC data and as an
      invaluable resource for clinical and non-clinical researchers. 

PMID- 26314592
TI  - Can Increasing the Manufacturer's Recommended Shortest Curing Time of High
      intensity Light-emitting Diodes Adequately Cure Sealants?
AB  - PURPOSE: To investigate sealant depth of cure after increasing the curing times
      of high-intensity light-emitting diode units (LEDs). METHODS: Three sealants
      (opaque-unfilled, opaque-filled, and clear-filled) were light cured in a covered
      slot mold with: (a) three LEDs (VALO, SmartLite, Fusion) for six to 15 seconds;
      and (b) a quartz-tungsten halogen (QTH) light for 40 seconds as a control (N=10).
      Twenty-four hours after light curing, microhardness was measured at the sealant
      surface and through the depth at 0.5 mm increments. Results were analyzed via
      analysis of variance followed by the Student-Newman-Keuls test (significance
      level 0.05). RESULTS: The opaque-filled and clear-filled sealants cured with VALO
      for six or nine seconds had hardness values that were statistically equivalent to
      or better than the QTH to a depth of 1.5 mm. Using Fusion for 10 seconds
      (exposure limit) did not adequately cure the three sealants beyond one mm.
      SmartLite at 15 seconds (maximum exposure period without overheating) did not
      adequately cure the sealants beyond 0.5 mm. CONCLUSIONS: Among the tested high
      intensity LEDs, only VALO at double or triple the manufacturers' shortest curing
      time (six or nine seconds) provided adequate curing of opaque-filled and clear
      filled sealants at 1.5 mm depth compared to the 40-second QTH light.

PMID- 26314593
TI  - In Vivo and In Vitro performance of Conventional Methods, DIAGNOdent, and an
      Electronic Caries Monitor for Occlusal Caries Detection in Primary Teeth.
AB  - PURPOSE: The purpose of this study was to evaluate and compare the clinical and
      laboratory performances of an electronic caries monitor (ECM-IV) and the
      DIAGNOdent device with that of conventional methods, including visual (VE) and
      radiographic examinations (RE), for the detection of occlusal caries in primary
      teeth. METHODS: Three different observers examined 200 primary molars before
      extraction (in vivo), immediately after extraction (in vitro 1), and 14 days
      after extraction (in vitro 2). Examinations were performed visually,
      radiographically using the DIAGNOdent and ECM-IV devices. RESULTS: Among all the
      methods, the ECM-IV yielded the highest sensitivity and Az (Area under the ROC
      curve) values at the enamel (D1) threshold and visual examination for dentin (D3)
      threshold. For reproducibility, the ECM-IV presented the highest Kappa values at
      the D1 threshold, and the DIAGNOdent presented the highest Kappa values at the D3
      threshold. Both devices presented high intraclass correlation coefficient values,
      although DIAGNOdent showed higher values than ECM-IV in all stages of the study
      and for all observers. CONCLUSION: Considering the importance of early
      identification of caries in primary teeth, the use of the ECM and DIAGNOdent
      devices, together with conventional examination methods, will increase the rate
      of identification of occlusal caries during routine clinic visits.

PMID- 26314594
TI  - A Novel Pilot Study of Internet-stored Videotapes and Pediatric Dentists
      Predicting Behavior of Preschoolers.
AB  - PURPOSE: The purpose of this pilot study was to evaluate a web-based technology
      as a means of clinical research in assessing pediatric dentists' accuracy in
      predicting patient behaviors during a clinical procedure based on pre-procedural
      behaviors shown in vignettes. METHODS: A private web-based server was used to
      house six two-minute vignettes and a questionnaire on children's behaviors and
      temperament characteristics. An electronic link via an e-mail invitation was sent
      to a sample of pediatric dentists. Six patients undergoing a clinical examination
      were pre-rated using the Ohio State Behavior Rating Scale and classified each as
      cooperative, potentially cooperative, and uncooperative. The vignettes displayed
      the children prior to undergoing an examination. Pediatric dentists were asked to
      predict the children's behaviors and temperament during the clinical examination
      based on the behavior in the vignettes. RESULTS: Results indicated that 89
      percent of the respondents were able to correctly classify and predict behaviors
      in at least four of the six vignettes. Respondents were less confident and
      accurate in their predictions for children who were rated as uncooperative (48
      percent and 33 percent, respectively). CONCLUSIONS: Web-based technology may be a
      promising tool for studies in pediatric dentistry. Pediatric dentists can rapidly
      perceive cues in classifying and discriminating behaviors.

PMID- 26314595
TI  - Quo Vadimus (Where are we going?).

PMID- 26314596
TI  - Letter to the Editor.

PMID- 26314597
TI  - Response to the Letter to the Editor.

PMID- 26314598
TI  - Is it Ethical to Withhold Restorative Dental Care From a Child with
      Occlusoproximal Caries Lesions Into Dentin of Primary Molars?
AB  - Non-restorative caries treatment (NRCT) has been mentioned as a treatment option
      for occluso-proximal caries lesions into dentin of primary molars. The NRCT
      approach for occluso-proximal caries lesions in primary molars was considered
      from an ethical perspective. In summary, it is not ethical to withhold
      restorative dental care from a child with occluso-proximal caries lesions into
      dentin of primary molars. 

PMID- 26314599
TI  - Interference of Antimicrobial Activity of Combinations of Oral Antiseptics
      Against Streptococcus mutans, Streptococcus sanguinis, and Lactobacillus
      acidophilus.
AB  - PURPOSE: The purpose of this study was to compare the effects of combinations of
      sodium fluoride and antiseptic compounds on the growth of Streptococcus mutans,
      Streptococcus sanguinis, and Lactobacillus acidophilus. METHODS: The agar
      diffusion assay was used to determine bacterial growth inhibition. RESULTS: Of
      the combinations tested, 0.1 percent sodium fluoride and five percent povidone
      iodine produced synergistic antibacterial effects against S. mutans and S.
      sanguinis. The combination of 10 percent povidone iodine and 0.5 percent sodium
      hypochlorite produced additive antibacterial effects against L. acidophilus.
      Interference was seen in some combinations such as 0.01 percent chlorhexidine and
      0.25 percent sodium lauryl sulphate, 0.5 percent sodium hypochlorite and 10
      percent povidone iodine, and 0.01 percent cetyl pyridium chloride and 0.1 percent
      sodium fluoride. However, 0.1 percent sodium fluoride combined with 0.01 percent
      chlorhexidine did not interfere with the antibacterial effects of chlorhexidine
      against S. mutans or S. sanguinis. CONCLUSIONS: Combinations of common
      antiseptics and fluoride compounds can produce interference, synergistic, or
      additive effects. The combination of 0.1 percent sodium fluoride and five percent
      povidone iodine had the greatest potential for suppression of S. mutans.

PMID- 26314600
TI  - In Vitro Retentive Effect of Groove, Sandblasting, and Cement Type on Stainless
      Steel Crowns in Primary Molars.
AB  - PURPOSE: The purpose of this study was to evaluate and compare the effect of
      placing vertical grooves, sandblasting, and luting cements on the retention of
      stainless steel crowns (SSCs). METHODS: Eighty extracted primary molars were
      mounted in acrylic blocks. Specimens were divided into Group 1 (RelyX U200) and
      Group 2 (Smart Cem2). Teeth in each group were further subdivided into Subgroup A
      (no vertical grooves and no sandblasting), Subgroup B (vertical grooves),
      Subgroup C (sandblasting of crowns), and Subgroup D (vertical grooves and
      sandblasting of crowns). After cementation, SSCs were pulled off using a
      universal testing machine. One-way analysis of variance was used for statistical
      analyses. RESULTS: In Groups 1 and 2, the highest retentive strengths were found
      in Subgroup D (1,124 and 783 kPa, respectively), followed by Subgroup C (1,066
      and 748 kPa, respectively), Subgroup A (762 and 356 kPa, respectively), and
      Subgroup B (743 and 314 kPa, respectively). Retentive strength in Group one was
      significantly higher than in Group two; Subgroups A and B were significantly
      lower than C and D. CONCLUSIONS: RelyX U200 showed higher retentive strength than
      Smart Cem2. Sandblasting increased the retention strength, whereas a vertical
      groove had no significant effect on retention.

PMID- 26314601
TI  - The Influence of Parenting Style and Child Temperament on Child-Parent-Dentist
      Interactions.
AB  - PURPOSE: This study aimed to investigate the interaction between parenting style
      and child's temperament as modulators of anxiety and behavior in children during
      the dental procedure. METHODS: Healthy four- to six-year-olds (n equals 288),
      with carious primary molars scheduled to receive amalgam fillings were selected.
      The Primary Caregivers Practices Report was used to assess the parenting style,
      and the Children's Behavior Questionnaire-Very Short Form was used to evaluate
      child temperament. Children were managed using common behavior management
      strategies. Child behavior and anxiety during the procedure were assessed using
      the Frankl behavior rating scale and the verbal skill scale, respectively.
      Spearman's correlation coefficient was used to examine the correlation among
      variables. RESULTS: Authoritative parenting style was positively related to
      positive child's behavior (P<.05) and negatively related to child's anxiety
      (P<.05). A positive relationship existed between permissive subscale and negative
      behaviors (P<.05) and child's anxiety (P<.05). There was a significant direct
      effect of authoritative parenting style on the effortful control trait (P<.05)
      and permissive parent style on the child negative affectivity (P<.05).
      CONCLUSIONS: Parenting style appeared to mediate child temperament and anxiety,
      and was related to the child's behavior. Parenting style should be considered in
      the selection of behavior guidance techniques.

PMID- 26314602
TI  - Epidemiology and Outcomes of Hospital-based Emergency Department Visits with
      Tooth Fractures.
AB  - PURPOSE: The purpose of this study was to identify characteristics of hospital
      based emergency department (ED) visits for tooth fracture and subsequent dentally
      related hospital admissions. METHODS: This was a retrospective analysis of the
      Nationwide Emergency Department Sample of the Healthcare Cost and Utilization
      Project for the years 2008 to 2010. All children up to 21 years old, with a
      diagnosis of tooth fracture due to trauma, were selected. Hospital ED charges,
      occurrence of concurrent injuries, and hospitalization following ED visits were
      examined. RESULTS: A total of 199,061 ED visits were attributed to broken or
      fractured teeth; males comprised 63 percent of ED visits. Skull and facial
      fractures were present in seven percent and intracranial injuries in four percent
      of ED visits. The most frequent causes for ED visits and for subsequent
      hospitalization, respectively, were falls and motor vehicle accidents. The mean
      charge for each ED visit was $1,441. Total charges for the entire United States
      were $241.8 million. Following an ED visit, 7,233 patients were admitted as
      inpatients. CONCLUSIONS: Males comprised a majority of these emergency department
      visits. Occurrence of concomitant bodily injuries appears to be common and is a
      significant predictor of hospitalization and hospital ED charges.

PMID- 26314603
TI  - Oral Health Status and Salivary Levels of Mutans Streptococci in Children with
      Down Syndrome.
AB  - PURPOSE: The literature on the oral health status of Down syndrome (DS) patients
      is controversial. Therefore, the purpose of this study was to assess the oral
      health status and levels of mutans streptococci (MS) in the saliva of DS
      children. METHODS: This study was performed with 60 DS children and 71 non-DS
      children aged six to 12 years old. Caries experience, plaque index (PI), and
      gingival bleeding index (GBI) were recorded. Information about oral hygiene
      habits was obtained. Saliva samples were collected to determine MS levels.
      RESULTS: The prevalence of dental caries was similar in children with and without
      DS. DS children had lower PI and GBI values and a higher toothbrushing frequency.
      Supervised toothbrushing by parents or guardians was more frequent in DS children
      and associated with lower PI and GBI. High counts of MS in saliva were associated
      with caries experience in DS children. CONCLUSIONS: Down syndrome children had a
      similar caries experience, lower plaque index, and lower gingival bleeding index
      values compared to children without Down syndrome. However, DS children who had
      caries were more likely to display high counts of mutans streptococci in saliva
      than non-DS children with caries.

PMID- 26314604
TI  - Evaluation of Pulp Chamber Dimensions of Primary Molars From Bitewing
      Radiographs.
AB  - PURPOSE: The purpose of this study was to measure key anatomic landmarks related
      to pulp chamber morphology in primary maxillary and mandibular first and second
      molars. METHODS: Bitewing radiographs of 42 subjects were taken under
      standardized conditions using a millimeter X-ray grid. One hundred fifty-three
      primary molars (44 maxillary first molars, 49 maxillary second molars, 30
      mandibular first molars, and 30 mandibular second molars) were analyzed for the
      required anatomic landmarks using Image J Analysis Software. The data were
      analyzed in terms of mean, standard deviation, and coefficient of variance for
      each measurement. Mean measurements were compared using one-way analysis of
      variance followed by Tukey's post-hoc HSD test. RESULTS: The distance between
      cusp tip to pulp chamber ceiling was approximately four mm, the distance between
      pulpal floor to furcation was approximately 1.7 mm, and the average height of the
      pulp chamber was observed to be in the range of two to three mm. CONCLUSION: The
      key measurements involved in access cavity preparation were consistent across the
      different types of primary molars.

PMID- 26314605
TI  - Retention of Moisture-tolerant and Conventional Resin-based Sealant in Six- to
      Nine-year-old Children.
AB  - PURPOSE: The purpose of this study was to evaluate and compare the retention
      rates and development of caries in permanent molars in children sealed with
      moisture-tolerant, resin-based (Embrace WetBond), and conventional resin-based
      (Helioseal) sealant over a period of one year. METHODS: This was a double blind,
      split-mouth, randomized controlled trial among six- to nine-year-olds. Sixty
      eight permanent mandibular first molars in 34 children were randomly assigned to
      be sealed with Embrace WetBond or Helioseal sealant. RESULTS: The final sample
      was 32 children with 64 teeth. At 12 months, 23 of 32 (72 percent) sealants were
      completely retained in Embrace WetBond, whereas only 16 of 32 (50 percent) were
      retained in the Helioseal group. There was a statistically significant difference
      in retention rates of Embrace WetBond and Helioseal sealants at 12 months
      (P<.05). At 12 months follow-up, only two teeth developed caries in Embrace
      WetBond; in the Helioseal group, five teeth developed caries (two initial and
      three enamel caries). CONCLUSIONS: Embrace WetBond was superior to Helioseal
      sealant, as Embrace exhibited higher retention and lower caries scores. Embrace
      WetBond can be preferred over conventional resin-based sealants for community and
      outreach sealant programs where use of rubber dam for moisture control is
      difficult to practice.

PMID- 26314606
TI  - Pediatric Dentist Density and Preventive Care Utilization for Medicaid Children.
AB  - PURPOSE: The purpose of this study was to evaluate county-level pediatric dentist
      density and dental care utilization for Medicaid-enrolled children. METHODS: This
      was a cross-sectional analysis of 604,885 zero- to 17-year-olds enrolled in the
      Washington State Medicaid Program for 11-12 months in 2012. The relationship
      between county-level pediatric dentist density, defined as the number of
      pediatric dentists per 10,000 Medicaid-enrolled children, and preventive dental
      care utilization was evaluated using linear regression models. RESULTS: In 2012,
      179 pediatric dentists practiced in 16 of the 39 counties in Washington. County
      level pediatric dentist density varied from zero to 5.98 pediatric dentists per
      10,000 Medicaid-enrolled children. County-level preventive dental care
      utilization ranged from 32 percent to 81 percent, with 62 percent of Medicaid
      enrolled children utilizing preventive dental services. County-level density was
      significantly associated with county-level dental care utilization (Slope equals
      1.67, 95 percent confidence interval equals 0.02, 3.32, P<.05). CONCLUSIONS:
      There is a significant relationship between pediatric dentist density and the
      proportion of Medicaid-enrolled children who utilize preventive dental care
      services. Policies aimed at improving pediatric oral health disparities should
      include strategies to increase the number of oral health care providers,
      including pediatric dentists, in geographic areas with large proportions of
      Medicaid-enrolled children.

PMID- 26314607
TI  - Cost-Benefit Analysis of the Age One Dental Visit for the Privately Insured.
AB  - PURPOSE: The purpose of this study was to perform a cost-benefit analysis of the
      age one dental visit for privately insured patients. METHODS: A major insurance
      company provided claims from various states submitted between 2006-2012. Data
      provided included numbers of procedures and respective costs from the first visit
      until age six years. Data was organized into five groups based on age, for which
      the first D0145/D0150 code was submitted [(1) age younger than one year old; (2)
      age one or older but younger than two years old; (3) age two or older but younger
      than three years old; (4) age three or older but younger than four years old; and
      (5) age four or older but younger than five years old]. The ratio of procedures
      per child and average costs per child were calculated. RESULTS: Claims for 94,574
      children were analyzed; only one percent of these children had their first dental
      visit by age one. The annual cost for children who had their first dental visit
      by age one was significantly less than for children who waited until an older
      age. CONCLUSION: There is an annual cost benefit in establishing a dental home by
      age one for privately insured patients.

PMID- 26314608
TI  - Coordinated Pediatric and Periodontal Dental Care of a Child with Down syndrome.
AB  - The purpose of this report was to describe the management of an eight-year-old
      Bulgarian male with Down syndrome presenting with periodontitis as a
      manifestation of systemic disease in the early mixed dentition. Treatment
      involved full-mouth mechanical debridement and extraction of hopeless teeth under
      general anesthesia followed by systemic antibiotics and chemical adjunctive
      therapy. Microbial culture and sensitivity testing aided in diagnosis and guided
      treatment decisions. This case report demonstrates a multidisciplinary approach
      in the management of aggressive periodontal disease in an internationally adopted
      pediatric patient with special health care needs. 

PMID- 26314609
TI  - Steam pretreatment of Saccharum officinarum L. bagasse by adding of impregnating
      agents for advanced bioethanol production.
AB  - The main byproduct of the sugarcane industry, Saccharum officinarum L. bagasse
      (sugarcane bagasse, SCB), is widely used as lignocellulose biomass for bio
      ethanol (EtOH) production. In this research study, SCB was pretreated by steam
      explosion (SE) method using two different impregnating agents: sulfur dioxide
      (SD) and hydrogen peroxide (HP). As matter of fact, the use of impregnating
      agents improves the performance of SE method, increasing the concentrations of
      fermentable sugars after enzymatic saccharification, and decreasing the inhibitor
      compounds produced during the steam pretreatment step. The aim of this study was
      to investigate and compare the use of the two impregnating agents in various SE
      conditions in order to optimize pretreatment parameters. For every pretreatment
      condition, it has been evaluated: concentration of fermentable sugars, glucose
      and xylose yields, and the effects of the inhibitor compounds on enzymatic
      hydrolysis step. The obtained results allow to improve the efficiency of the
      whole process of bio-EtOH synthesis enhancing the amount of fermentable sugars
      produced and the eco-sustainability of the whole process. Indeed, the
      optimization of steam pretreatment leads to a reduction of energy requirements
      and to a lower environmental impact.

PMID- 26314610
TI  - T-786C single nucleotide polymorphism of the endothelial nitric oxide synthase
      gene as a risk factor for endothelial dysfunction in polymyalgia rheumatica.
AB  - OBJECTIVES: We investigated the association of the T-786C single nucleotide
      polymorphism (SNP) of the endothelial nitric oxide synthase gene (NOS3), which is
      characterised by reduced expression of the enzyme in response to shear stress or
      interleukin-10 stimulation and significantly associated with coronary heart
      disease or rheumatoid arthritis, with the occurrence of isolated polymyalgia
      rheumatica. METHODS: A cohort of 78 patients who had presented at a
      rheumatological specialist practice in Heidelberg was tested for the T-786C SNP
      by means of restriction fragment length polymorphism analysis, and the result was
      compared with the data of a control cohort (n=2061) compiled from the genotyping
      of umbilical cord arteries from newborns. Patients were tested for an association
      with the genotype and their clinical characteristics obtained at the time of the
      initial presentation and during the first year of treatment. RESULTS: The T-786C
      SNP of the NOS3 gene was significantly associated with isolated PMR (p=0.0009; OR
      2.475). The C-allele frequency in patients with PMR was higher than in patients
      with rheumatoid arthritis, who also showed a significant association with the T
      786C SNP (PMR 0.481 vs. 0.422 RA). A significant association with clinical
      features of the patients could not be detected. CONCLUSIONS: The T-786C SNP of
      the NOS3 gene, which predisposes towards the development of endothelial
      dysfunction, is significantly associated with polymyalgia rheumatica manifesting
      itself without any clinically detectable vascular involvement.

PMID- 26314611
TI  - The importance of pelvic nerve fibers in endometriosis.
AB  - Several lines of recent evidence suggest that pelvic innervation is altered in
      endometriosis-affected women, and there is a strong presumption that nerve fibers
      demonstrated in eutopic endometrium (of women with endometriosis) and in
      endometriotic lesions play roles in the generation of chronic pelvic pain. The
      recent observation of sensory C, sensory A-delta, sympathetic and parasympathetic
      nerve fibers in the functional layer of endometrium of most women affected by
      endometriosis, but not demonstrated in most women who do not have endometriosis,
      was a surprise. Nerve fiber densities were also greatly increased in myometrium
      of women with endometriosis and in endometriotic lesions compared with normal
      peritoneum. Chronic pelvic pain is complex, and endometriosis is only one
      condition which contributes to this pain. The relationship between the presence
      of certain nerve fibers and the potential for local pain generation requires much
      future research. This paper reviews current knowledge concerning nerve fibers in
      endometrium, myometrium and endometriotic lesions, and discusses avenues of
      research that may improve our knowledge and lead to enriched understanding and
      management of endometriotic pain symptoms. 

PMID- 26314612
TI  - Single-molecule magnet behaviour in polynuclear assembly of trivalent cerium ions
      with polyoxomolybdates.
AB  - An isopolyoxomolybdate-based POM is coordinated to trivalent cerium ions to
      afford a hybrid complex namely, [Ce(dmso)8][Ce(eta2-NO3)2(dmso)4(alpha
      Mo8O26)0.5][Mo6O19]. The original electrostatic environment created around the
      Ce(III) by its coordination to the isopolyoxomolybdate core induces complex
      single-molecule magnet behavior. 

PMID- 26314613
TI  - Ultrafast time-resolved electron diffraction revealing the nonthermal dynamics of
      near-UV photoexcitation-induced amorphization in Ge2Sb2Te5.
AB  - Because of their robust switching capability, chalcogenide glass materials have
      been used for a wide range of applications, including optical storages devices.
      These phase transitions are achieved by laser irradiation via thermal processes.
      Recent studies have suggested the potential of nonthermal phase transitions in
      the chalcogenide glass material Ge2Sb2Te5 triggered by ultrashort optical pulses;
      however, a detailed understanding of the amorphization and damage mechanisms
      governed by nonthermal processes is still lacking. Here we performed ultrafast
      time-resolved electron diffraction and single-shot optical pump-probe
      measurements followed by femtosecond near-ultraviolet pulse irradiation to study
      the structural dynamics of polycrystalline Ge2Sb2Te5. The experimental results
      present a nonthermal crystal-to-amorphous phase transition of Ge2Sb2Te5 initiated
      by the displacements of Ge atoms. Above the fluence threshold, we found that the
      permanent amorphization caused by multi-displacement effects is accompanied by a
      partial hexagonal crystallization. 

PMID- 26314615
TI  - The mortality patterns of lung cancer between 1990 and 2013 in Xuanwei, China.
AB  - OBJECTIVES: To explore the variations in the mortality trends, especially death
      due to lung cancer, from 1990 to 2013 in Xuanwei City. MATERIALS AND METHODS:
      Mortality data were collected in Xuanwei during the 2nd and 3rd National
      Retrospective Sampling Survey on Mortality and Routine Death Registration System
      (DRS) during 2011-2013. According to the result of the survey on under-reported
      deaths, mortality data from DRS during 2011-2013 were adjusted. Disease specific
      mortality rate, age-standardized mortality rate (ASMR) and 45Q15 were calculated
      in Xuanwei and compared with those in rural areas of China. RESULTS: During three
      periods, 1990-1992, 2004-2005 and 2011-2013, lung cancer contributed to 56.86%,
      58.45% and 63.03% of deaths from all cancers respectively with a much higher
      proportion than rural areas nationally. The ASMR of lung cancer for males surged
      from 41.43/10(5) to 88.17/10(5) during 1990-2005 and it surged from 37.70/10(5)
      to 74.45/10(5) for females. Although they declined slightly during 2011-2013
      (82.53/10(5) and 62.62/10(5) for males and females respectively), the ASMR of
      lung cancer among males in Xuanwei was three times of that in rural areas in
      China, and it was six times higher among females. The 45Q15 of lung cancer for
      males in Xuanwei was 3-5 times of that in rural areas of China and for females it
      was 7-9 times. The high-mortality areas of lung cancer were still located in
      Laibin, Longchang, Wanshui and Shuanglong Communities. High-mortality areas of
      lung cancer expanded to their surrounding areas and those in southeast.
      CONCLUSIONS: Although indoor air pollution caused by smoky coal has been fairly
      well controlled, patterns of death due to lung cancer have not obviously changed.
      The mortality rate of lung cancer among females was similar to that among males.
      Therefore, further studies should be conducted to comprehensively explore the
      risk factors of lung cancer in Xuanwei.

PMID- 26314616
TI  - Radiation-induced formation of Co3O4 nanoparticles from Co(2+)(aq): probing the
      kinetics using radical scavengers.
AB  - The effects of the Co(2+) content and different radical scavengers on the
      kinetics of gamma-radiation-induced Co3O4 nanoparticle formation and growth were
      investigated. There are four distinct stages of particle formation with different
      oxidation rates. Scavengers and [Co(2+)]0 affect the oxidation kinetics in the
      different stages and consequently the final size of the particles formed.
      Radiolysis model calculations were performed to obtain the time-evolution of the
      concentrations of key oxidants and reductants, and the effect of scavengers on
      those concentrations. Based on the model results and experimental data a reaction
      mechanism for Co3O4 particle formation by gamma-irradiation of solutions
      containing Co(2+)(aq) is proposed. The main cobalt oxidation reaction changes
      with time. Oxidation of Co(2+)(aq) to Co(3+)(aq) by radiolytically produced OH
      occurs first in the solution phase. This is followed by spontaneous co
      precipitation of mixed Co(II)/Co(III) hydroxide nucleate particles. Adsorption of
      Co(II)(ad) followed by surface oxidation of Co(II)(ad) to CoOOH(ad) by H2O2 grows
      particles with a solid CoOOH(s) phase. In parallel, the solid-state
      transformation of CoOOH(s) and Co(II)(ad) to form Co3O4(s) occurs. 

PMID- 26314617
TI  - Reply to Michael Froehner, Rainer Koch, Manfred P. Wirth's Letter to the Editor
      re: Malte Rieken, Shahrokh F. Shariat, Luis A. Kluth, et al. Association of
      Cigarette Smoking and Smoking Cessation with Biochemical Recurrence of Prostate
      Cancer in Patients Treated with Radical Prostatectomy. Eur Urol. In press.
      http://dx.doi.org/10.1016/j.eururo.2015.05.038.

PMID- 26314614
TI  - Adherence to AIOM (Italian Association of Medical Oncology) lung cancer
      guidelines in Italian clinical practice: Results from the RIGHT-3 (research for
      the identification of the most effective and highly accepted clinical guidelines
      for cancer treatment) study.
AB  - OBJECTIVES: Clinical practice guidelines represent a key tool to improve quality
      and reduce variability of cancer care. In 2004, Italian Association of Medical
      Oncology (AIOM) launched the RIGHT (research for the identification of the most
      effective and highly accepted clinical guidelines for cancer treatment) program.
      The third step, RIGHT-3, evaluated the concordance between AIOM lung cancer
      guidelines and Italian clinical practice. MATERIALS AND METHODS: RIGHT-3 was a
      retrospective observational study, conducted in 53 Italian centers treating lung
      cancer. Sampling from AIOM database of 230 centers was stratified by presence of
      thoracic surgery and geographic distribution. To describe the adherence to AIOM
      guidelines (2009 edition), 11 indicators regarding diagnostic and treatment
      procedures were identified. Patients with non-small-cell lung cancer (NSCLC)
      diagnosis who had first visit in 2010 were divided into 3 groups, based on TNM
      stage: I-II-IIIA (5 indicators), IIIB (3 indicators) and IV (3 indicators).
      RESULTS: 708 patients were enrolled; 680 were eligible: 225 patients in stage I
      II-IIIA; 156 patients in stage IIIB; 299 patients in stage IV. Cyto-histological
      diagnosis was available in 96%, 97%, 96% of stage I-II-IIIA, IIIB, IV
      respectively. Positron-emission tomography was performed in 64% of stage I-II
      IIIA and 46% of stage IIIB. 88% of stage I-II patients eligible for surgery
      underwent lobectomy; after surgery, 61% of stage II and 57% of stage IIIA
      patients received adjuvant chemotherapy. Among stage IIIB patients who received
      combined chemo- radiotherapy, sequential approach was more common than
      concomitant treatment (86% vs. 14%). Among stage IV patients, 87% received
      platinum-based first-line treatment, and 70% received second-line. CONCLUSION:
      The RIGHT-3 study showed that, in 2010, adherence to Italian NSCLC guidelines was
      high for many indicators (including those related to treatment of stage IV
      patients), but lower for some diagnostic procedures. Guidelines adherence
      monitoring can be useful to reduce variability in cancer care.

PMID- 26314618
TI  - Gene expression and pathway analysis of human hepatocellular carcinoma cells
      treated with cadmium.
AB  - Cadmium (Cd) is a toxic and carcinogenic metal naturally occurring in the Earth's
      crust. A common route of human exposure is via diet and cadmium accumulates in
      the liver. The effects of Cd exposure on gene expression in human hepatocellular
      carcinoma (HepG2) cells were examined in this study. HepG2 cells were acutely
      treated with 0.1, 0.5, or 1.0 MUM Cd for 24h; or chronically-treated with 0.01,
      0.05, or 0.1 MUM Cd for three weeks and gene expression analysis was performed
      using Affymetrix GeneChip(r) Human Gene 1.0 ST Arrays. Acute and chronic
      exposures significantly altered the expression of 333 and 181 genes,
      respectively. The genes most upregulated by acute exposure included several
      metallothioneins. Downregulated genes included the monooxygenase CYP3A7, involved
      in drug and lipid metabolism. In contrast, CYP3A7 was upregulated by chronic Cd
      exposure, as was DNAJB9, an anti-apoptotic J protein. Genes downregulated
      following chronic exposure included the transcriptional regulator early growth
      response protein 1. Ingenuity Pathway Analysis revealed that the top networks
      altered by acute exposure were lipid metabolism, small molecule biosynthesis,
      cell morphology, organization, and development; while top networks altered by
      chronic exposure were organ morphology, cell cycle, cell signaling, and renal and
      urological diseases/cancer. Many of the dysregulated genes play important roles
      in cellular growth, proliferation, and apoptosis, and may be involved in
      carcinogenesis. In addition to gene expression changes, HepG2 cells treated with
      cadmium for 24h indicated a reduction in global levels of histone methylation and
      acetylation that persisted 72 h post-treatment.

PMID- 26314619
TI  - Developmental neurotoxic effects of two pesticides: Behavior and biomolecular
      studies on chlorpyrifos and carbaryl.
AB  - In recent times, an increased occurrence of neurodevelopmental disorders, such as
      neurodevelopmental delays and cognitive abnormalities has been recognized.
      Exposure to pesticides has been suspected to be a possible cause of these
      disorders, as these compounds target the nervous system of pests. Due to the
      similarities of brain development and composition, these pesticides may also be
      neurotoxic to humans. We studied two different pesticides, chlorpyrifos and
      carbaryl, which specifically inhibit acetylcholinesterase (AChE) in the nervous
      system. The aim of the study was to investigate if the pesticides can induce
      neurotoxic effects, when exposure occurs during a period of rapid brain growth
      and maturation. The results from the present study show that both compounds can
      affect protein levels in the developing brain and induce persistent adult
      behavior and cognitive impairments, in mice neonatally exposed to a single oral
      dose of chlorpyrifos (0.1, 1.0 or 5mg/kg body weight) or carbaryl (0.5, 5.0 or
      20.0mg/kg body weight) on postnatal day 10. The results also indicate that the
      developmental neurotoxic effects induced are not related to the classical
      mechanism of acute cholinergic hyperstimulation, as the AChE inhibition level (8
      12%) remained below the threshold for causing systemic toxicity. The neurotoxic
      effects are more likely caused by a disturbed neurodevelopment, as similar
      behavioral neurotoxic effects have been reported in studies with pesticides such
      as organochlorines, organophosphates, pyrethroids and POPs, when exposed during a
      critical window of neonatal brain development. 

PMID- 26314620
TI  - Towards nanoprinting with metals on graphene.
AB  - Graphene and carbon nanotubes are envisaged as suitable materials for the
      fabrication of the new generation of nanoelectronics. The controlled patterning
      of such nanostructures with metal nanoparticles is conditioned by the transfer
      between a recipient and the surface to pattern. Electromigration under the impact
      of an applied voltage stands at the base of printing discrete digits at the
      nanoscale. Here we report the use of carbon nanotubes as nanoreservoirs for iron
      nanoparticles transfer on few-layer graphene. An initial Joule-induced annealing
      is required to ensure the control of the mass transfer with the nanotube acting
      as a 'pen' for the writing process. By applying a voltage, the tube filled with
      metal nanoparticles can deposit metal on the surface of the graphene sheet at
      precise locations. The reverse transfer of nanoparticles from the graphene
      surface to the nanotube when changing the voltage polarity opens the way for
      error corrections. 

PMID- 26314621
TI  - Latent Cytomegalovirus Infection in Rheumatoid Arthritis and Increased
      Frequencies of Cytolytic LIR-1+CD8+ T Cells.
AB  - OBJECTIVE: Leukocyte immunoglobulin-like receptor 1 (LIR-1) is up-regulated by
      cytomegalovirus (CMV), which in turn, has been associated with premature aging
      and more severe joint disease in patients with rheumatoid arthritis (RA). The aim
      of this study was to investigate the expression and functional significance of
      LIR-1 in CMV-positive RA patients. METHODS: We determined the phenotype,
      cytolytic potential, CMV-specific proliferation, and HLA-G-triggered, LIR-1
      mediated inhibition of interferon-gamma secretion of LIR-1+ T cells in RA
      patients and healthy controls. RESULTS: We found increased frequencies of CD8+ T
      cells with CMV pp65-specific T cell receptors in CMV-positive RA patients as
      compared to CMV-positive healthy controls. CMV-specific CD8+ T cells in these
      patients were preferentially LIR-1+ and exhibited a terminally differentiated
      polyfunctional phenotype. The numbers of LIR-1+CD8+ T cells increased with age
      and disease activity, and showed high levels of reactivity to CMV antigens.
      Ligation of LIR-1 with soluble HLA-G molecules in vitro confirmed an inhibitory
      role of the molecule when expressed on CD8+ T cells in RA patients. CONCLUSION:
      We propose that latent CMV infection in the context of a chronic autoimmune
      response induces the recently described "chronic infection phenotype" in CD8+ T
      cells, which retains anti-infectious effector features while exhibiting
      autoreactive cytolytic potential. This response is likely dampened by LIR-1 to
      avoid overwhelming immunopathologic changes in the setting of the autoimmune
      disease RA. The known deficiency of soluble HLA-G in RA and the observed
      association of LIR-1 expression with disease activity suggest, however, that LIR
      1+ T cells are insufficiently controlled in RA and are still likely to be
      involved in the pathogenesis of the disease.

PMID- 26314622
TI  - Healthcare utilisation of pregnant women who experience sciatica, leg cramps
      and/or varicose veins: A cross-sectional survey of 1835 pregnant women.
AB  - BACKGROUND: Common discomforts of pregnancy experienced in the lower extremity
      include sciatica, leg cramps and varicose veins. Whilst research attention has
      focused on aetiology and outcomes, the health service utilisation of pregnant
      women suffering from these complaints has been largely overlooked. AIM: To
      examine the health status and health service utilisation profile of pregnant
      women experiencing sciatica, leg cramps or varicose veins. METHODS: Linear and
      logistic regression was applied to a cross-sectional survey of a pregnant women
      drawn from the 1973 to 1978 cohort (aged 31-36 years in 2009), of the Australian
      Longitudinal Study on Women's Health (n=1835). Participant's demographics, health
      status and health service utilisation were compared for all three complaints
      based upon three subgroups (yes, sought help; yes, did not seek help; no).
      FINDINGS: A number of women experienced sciatica (22.1%), leg cramps (18.2%) or
      varicose veins (9.4%). Of these, a greater proportion of women with sciatica
      (79.3%) or varicose veins (71.5%) sought help for their condition compared with
      women with leg cramps (46.7%). Comparisons between women with the conditions of
      interest who did seek help and those who did not only found that women with a
      university degree were 0.29 (95% CI: 0.10, 0.85) times less likely to seek help
      for their condition compared to women with a school only education. CONCLUSION:
      Further research examining all health seeking behaviour and treatment use of
      pregnant women who experience lower extremity problems is required in order to
      facilitate safe, effective and coordinated maternity care to further support
      these women during pregnancy.

PMID- 26314623
TI  - Natural history and epidemiology of respiratory syncytial virus infection in the
      Middle East: Hospital surveillance for children under age two in Jordan.
AB  - Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and viral
      pneumonia in infants and young children worldwide. In the Middle East and Arab
      countries, the burden of RSV-associated hospitalizations is not well
      characterized. We sought to determine the burden and clinical/epidemiological
      characteristics of RSV hospitalization in young children in Amman, Jordan. We
      investigated risk factors for severity including vitamin D levels. METHODS: We
      conducted viral surveillance with clinical and demographic data in children <2
      years admitted with respiratory symptoms and/or fever at the Al-Bashir Government
      Hospital from March16, 2010 to March 31, 2013. Nasal/throat swabs were obtained
      and placed into lysis buffer, and frozen at -80 degrees C until testing by real
      time RT-PCR for 11 respiratory viruses. Heel stick blood or sera samples for 25
      hydroxyvitamin D [25(OH)D] levels were obtained and sent to a central laboratory
      for mass spectrometry. RESULTS: Of the 3168 children, >80% testing positive for
      one virus, with RSV the most common virus detected (44%). The RSV-associated
      hospitalization rate was highest in children <6 months with an annual range of
      21.1-25.9 per 1000, compared to 6.0-8.0 in 6-11-month-olds and 1.6-2.5 in 12-23
      month-olds. RSV-positive children compared with RSV-negative were more likely to
      be previously healthy without underlying medical conditions, less likely to be
      born prematurely, had a higher frequency of supplemental oxygen use, and had
      lower median vitamin D levels. Risk factors for oxygen use in RSV-positive
      children included underlying medical conditions, lack of breastfeeding, younger
      age, and higher viral load. CONCLUSION: RSV is a major cause of illness in
      hospitalized Jordanian children and is associated with increased severity
      compared to other respiratory viruses. Children with RSV in the Middle East would
      benefit from future RSV vaccines and antiviral therapy.

PMID- 26314624
TI  - Molecular characterization of the 17D-204 yellow fever vaccine.
AB  - INTRODUCTION: The worldwide use of yellow fever (YF) live attenuated vaccines
      came recently under close scrutiny as rare but serious adverse events have been
      reported. The population identified at major risk for these safety issues were
      extreme ages and immunocompromised subjects. Study NCT01426243 conducted by the
      French National Agency for AIDS research is an ongoing interventional study to
      evaluate the safety of the vaccine and the specific immune responses in HIV
      infected patients following 17D-204 vaccination. As a preliminary study, we
      characterized the molecular diversity from E gene of the single 17D-204 vaccine
      batch used in this clinical study. MATERIALS AND METHODS: Eight vials of
      lyophilized 17D-204 vaccine (Stamaril, Sanofi-Pasteur, Lyon, France) of the E5499
      batch were reconstituted for viral quantification, cloning and sequencing of
      C/prM/E region. RESULTS: The average rate of virions per vial was 8.68 +/- 0.07
      log10 genome equivalents with a low coefficient of variation (0.81%). 246
      sequences of the C/prM/E region (29-33 per vials) were generated and analyzed for
      the eight vials, 25 (10%) being defective and excluded from analyses. 95% of
      sequences had at least one nucleotide mutation. The mutations were observed on
      662 variant sites distributed through all over the 1995 nucleotides sequence and
      were mainly non-synonymous (66%). Genome variability between vaccine vials was
      highly homogeneous with a nucleotide distance ranging from 0.29% to 0.41%.
      Average p-distances observed for each vial were also homogeneous, ranging from
      0.15% to 0.31%. CONCLUSION: This study showed a homogenous YF virus RNA quantity
      in vaccine vials within a single lot and a low clonal diversity inter and intra
      vaccine vials. These results are consistent with a recent study showing that the
      main mechanism of attenuation resulted in the loss of diversity in the YF virus
      quasi-species.

PMID- 26314625
TI  - Immunogenicity and safety of a cell culture-derived inactivated trivalent
      influenza vaccine (NBP607): A randomized, double-blind, multi-center, phase 3
      clinical trial.
AB  - BACKGROUND: Cell culture-derived influenza vaccines (CCIVs) have several
      important advantages over egg-based influenza vaccines, including shorter
      production time, better preservation of wild-type virus antigenicity and large
      scale production capacity. METHODS: A randomized, double-blind, phase 3 trial was
      undertaken to evaluate the immunogenicity and safety of a novel cell culture
      derived inactivated, subunit, trivalent influenza vaccine (NBP607, SK Chemicals,
      Seongnam, Korea) compared to the control vaccine (AgrippalS1, Novartis Vaccines
      and Diagnostics Srl, Siena, Italy) among healthy adults aged 19 years or older
      (Clinical trial Number-NCT02344134). Immunogenicity was determined at pre
      vaccination, 1 month and 6 month post-vaccination by the hemagglutination
      inhibition assay. Solicited and unsolicited adverse events were assessed after
      vaccination. RESULTS: A total of 1156 healthy subjects were recruited. NBP607 met
      all of the criteria of Committee for Medicinal Products for Human Use (CHMP) at
      21 days post-vaccination. Contrary to NBP607, the control vaccine did not satisfy
      the seroconversion criteria for influenza B irrespective of age. Although the
      geometric mean titer for each influenza subtype declined gradually,
      seroprotection rate still remained >=80% for all subtypes up to six month after
      NBP607 administration. NBP607 recipients met the seroprotection criteria for all
      three influenza subtypes up to 6 month post-vaccination. There was no significant
      difference in the occurrence of adverse events between the NBP607 and control
      groups. CONCLUSION: NBP607, a novel CCIV, showed excellent immunogenicity that
      lasted >=6 months after vaccination and had tolerable safety profiles. In
      particular, NBP607 was more immunogenic against influenza B compared to the
      control, an egg-based subunit vaccine.

PMID- 26314626
TI  - Path to impact: A report from the Bill and Melinda Gates Foundation convening on
      maternal immunization in resource-limited settings; Berlin - January 29-30, 2015.
AB  - Global initiatives such as the Millennium Development Goals have led to major
      improvements in the health of women and children, and significant reductions in
      childhood mortality. Worldwide, maternal mortality has decreased by 45% and under
      five mortality has fallen by over 50% over the past two decades [1]. However,
      improvements have not been achieved evenly across all ages; since 1990, under
      five mortality has declined by ~5% annually, but the average decrease in neonatal
      mortality is only ~3% per year. Against this background, the Bill and Melinda
      Gates Foundation (BMGF) convened a meeting in Berlin on January 29-30, 2015 of
      global health stakeholders, representing funders, academia, regulatory agencies,
      non-governmental organizations, vaccine manufacturers, and Ministries of Health
      from Africa and Asia. The topic of discussion was the potential of maternal
      immunization (MI) to achieve further improvements in under-five morbidity and
      mortality rates in children, and particularly neonates and young infants, through
      targeting infectious diseases that are not preventable by other interventions in
      these age groups. The meeting focused on effective and appropriately priced MI
      vaccines against influenza, pertussis, and tetanus, as well as against
      respiratory syncytial virus, and the group B Streptococcus, for which no licensed
      vaccines currently exist. The primary goals of the BMGF 2015 convening were to
      bring together the global stakeholders in vaccine development, policy and
      delivery together with the Maternal, Newborn and Child Health (MNCH) community,
      to get recognition that MI is a strategy shared between these groups and so
      encourage increased collaboration, and obtain alignment on the next steps toward
      achieving a significant health impact through implementation of a MI program. 

PMID- 26314627
TI  - Targeted vaccination in healthy school children - Can primary school vaccination
      alone control influenza?
AB  - BACKGROUND: The UK commenced an extension to the seasonal influenza vaccination
      policy in autumn 2014 that will eventually see all healthy children between the
      ages of 2-16 years offered annual influenza vaccination. Models suggest that the
      new policy will be both highly effective at reducing the burden of influenza as
      well as cost-effective. We explore whether targeting vaccination at either
      primary or secondary schools would be more effective and/or cost-effective than
      the current strategy. METHODS: An age-structured deterministic transmission
      dynamic SEIR-type mathematical model was used to simulate a national influenza
      outbreak in England. Costs including GP consultations, hospitalisations due to
      influenza and vaccinations were compared to potential gains in quality-adjusted
      life years achieved through vaccinating healthy children. Costs and benefits of
      the new JCVI vaccination policy were estimated over a single season, and compared
      to the hypothesised new policies of targeted and heterogeneous vaccination.
      FINDINGS AND CONCLUSION: All potential vaccination policies were highly cost
      effective. Influenza transmission can be eliminated for a particular season by
      vaccinating both primary and secondary school children, but not by vaccinating
      only one group. The most cost-effective policy overall is heterogeneous
      vaccination coverage with 48% uptake in primary schools and 34% in secondary
      schools. The Joint Committee on Vaccination and Immunisation can consider a
      modification to their policy of offering seasonal influenza vaccinations to all
      healthy children of ages 2-16 years.

PMID- 26314628
TI  - Effect of acute ethanol administration on zebrafish tail-beat motion.
AB  - Zebrafish is becoming a species of choice in neurobiological and behavioral
      studies of alcohol-related disorders. In these efforts, the activity of adult
      zebrafish is typically quantified using indirect activity measures that are
      either scored manually or identified automatically from the fish trajectory. The
      analysis of such activity measures has produced important insight into the effect
      of acute ethanol exposure on individual and social behavior of this vertebrate
      species. Here, we leverage a recently developed tracking algorithm that
      reconstructs fish body shape to investigate the effect of acute ethanol
      administration on zebrafish tail-beat motion in terms of amplitude and frequency.
      Our results demonstrate a significant effect of ethanol on the tail-beat
      amplitude as well as the tail-beat frequency, both of which were found to
      robustly decrease for high ethanol concentrations. Such a direct measurement of
      zebrafish motor functions is in agreement with evidence based on indirect
      activity measures, offering a complementary perspective in behavioral screening. 

PMID- 26314629
TI  - High postnatal susceptibility of hippocampal cytoskeleton in response to ethanol
      exposure during pregnancy and lactation.
AB  - Ethanol exposure to offspring during pregnancy and lactation leads to
      developmental disorders, including central nervous system dysfunction. In the
      present work, we have studied the effect of chronic ethanol exposure during
      pregnancy and lactation on the phosphorylating system associated with the
      astrocytic and neuronal intermediate filament (IF) proteins: glial fibrillary
      acidic protein (GFAP), and neurofilament (NF) subunits of low, medium, and high
      molecular weight (NFL, NFM, and NFH, respectively) in 9- and 21-day-old pups.
      Female rats were fed with 20% ethanol in their drinking water during pregnancy
      and lactation. The homeostasis of the IF phosphorylation was not altered in the
      cerebral cortex, cerebellum, or hippocampus of 9-day-old pups. However, GFAP,
      NFL, and NFM were hyperphosphorylated in the hippocampus of 21-day-old pups. PKA
      had been activated in the hippocampus, and Ser55 in the N-terminal region of NFL
      was hyperphosphorylated. In addition, JNK/MAPK was activated and KSP repeats in
      the C-terminal region of NFM were hyperphosphorylated in the hippocampus of 21
      day-old pups. Decreased NFH immunocontent but an unaltered total NFH/phosphoNFH
      ratio suggested altered stoichiometry of NFs in the hippocampus of ethanol
      exposed 21-day-old pups. In contrast to the high susceptibility of hippocampal
      cytoskeleton in developing rats, the homeostasis of the cytoskeleton of ethanol
      fed adult females was not altered. Disruption of the cytoskeletal homeostasis in
      neural cells supports the view that regions of the brain are differentially
      vulnerable to alcohol insult during pregnancy and lactation, suggesting that
      modulation of JNK/MAPK and PKA signaling cascades target the hippocampal
      cytoskeleton in a window of vulnerability in 21-day-old pups. Our findings are
      relevant, since disruption of the cytoskeleton in immature hippocampus could
      contribute to later hippocampal damage associated with ethanol toxicity. 

PMID- 26314630
TI  - Housing condition-related changes involved in reversal learning and its c-Fos
      associated activity in the prefrontal cortex.
AB  - Our study examined how different housing conditions modulated the acquisition of
      a spatial reference memory task and also, a reversal task in the 4-radial arm
      water maze (4-RAWM). The animals were randomly assigned to standard or enriched
      cages, and, as a type of complementary stimulation along with the environmental
      enrichment (EE), a group of rats also ran 15 min/day in a Rotarod. Elevated-zero
      maze results allowed us to discard that our exercise training increased anxiety
      related behaviors. 4-RAWM results revealed that the non-enriched group had a
      worse performance during the acquisition and also, during the first trial of each
      session with respect to the enriched groups. Regarding the reversal task, this
      group made more perseverative errors in the previous platform position.
      Interestingly, we hardly found differences between the two enriched groups (with
      and without exercise). We also analyzed how the reversal learning, depending on
      the previous housing condition, modulated the expression of c-Fos-positive nuclei
      in different subdivisions of the medial prefrontal cortex (cingulate (Cg),
      prelimbic (PL) and infralimbic (IL) cortices) and in the orbitofrontal (OF)
      cortex. The enriched groups had higher c-Fos expression in the Cg and OF cortices
      and lower in the IL cortex respect to the non-enriched animals. In the PL cortex,
      we did not find significant differences between the groups that performed the
      reversal task. Therefore, our short EE protocol improved the performance in a
      spatial memory and a reversal task, whereas the exercise training, combined with
      the EE, did not produce a greater benefit. This better performance seemed to be
      related with the specific pattern of c-Fos expression in brain regions involved
      in cognitive flexibility.

PMID- 26314633
TI  - Serotonergic interaction between medial prefrontal cortex and mesotelencephalic
      DA system underlies cognitive and affective deficits in hemiparkinsonian rats.
AB  - Parkinson's disease (PD) patients not only exhibit motor impairments, but also
      characteristic deficits in cognitive and affective functions. Such functions have
      consistently been associated with the medial prefrontal cortex (mPFC). To
      determine whether there is an interaction between the midbrain dopamine system
      (MDS) and the mPFC underlying the cognitive and emotional deficits seen in rats,
      we administered a disconnection procedure of these structures by applying lesions
      to the mPFC (N-methyl-d-aspartic acid (NMDA)) and the medial forebrain bundle (6
      hydroxydopamine (6-OHDA)) either in the same or opposite hemispheres. The results
      indicate a functional interaction of the MDS and the mPFC: Disconnection effects
      on behavior were observed with respect to memory-, anxiety- and depression
      related behaviors. A disconnection of the mPFC and MDS had promnestic,
      antidepressant- and anxiolytic-like effects. In order to determine whether this
      circuit between the mPFC and MDS involves serotonergic mechanisms, we also
      utilized serotonin-specific disconnections of the mPFC by applying the 5-HT
      specific agent 5,7-dihydroxytryptamine (5,7-DHT) into the mPFC and 6-OHDA into
      the medial forebrain bundle, again either in the same or opposite hemispheres.
      The behavioral effects observed here resembled those incurred by the unspecific
      disconnection of the mPFC, demonstrating a significant contribution of
      serotonergic mechanisms to the interplay between the MDS and the mPFC. Taken
      together, these experiments provide evidence for an interaction of the MDS and
      the mPFC in the control of cognitive and affective processes known to be impaired
      in PD and point toward a prominent involvement of the serotonergic system. A
      disconnection of the mPFC and the MDS had promnestic, antidepressant- and
      anxiolytic-like behavioral effects. These findings may impact therapeutic
      approaches in the treatment of cognitive and neuropsychiatric symptoms seen in
      PD. 

PMID- 26314634
TI  - 14-3-3 inhibition promotes dopaminergic neuron loss and 14-3-3theta
      overexpression promotes recovery in the MPTP mouse model of Parkinson's disease.
AB  - 14-3-3s are a highly conserved protein family that plays important roles in cell
      survival and interact with several proteins implicated in Parkinson's disease
      (PD). Disruption of 14-3-3 expression and function has been implicated in the
      pathogenesis of PD. We have previously shown that increasing the expression level
      of 14-3-3theta is protective against rotenone and 1-methyl-4-phenylpyridinium
      (MPP(+)) in cultured cells. Here, we extend our studies to examine the effects of
      14-3-3s in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of
      PD. We first investigated whether targeted nigral 14-3-3theta overexpression
      mediated by adeno-associated virus offers neuroprotection against MPTP-induced
      toxicity. 14-3-3theta overexpression using this approach did not reduce MPTP
      induced dopaminergic cell loss in the substantia nigra nor the depletion of
      dopamine (DA) and its metabolites in the striatum at three weeks after MPTP
      administration. However, 14-3-3theta-overexpressing mice showed a later partial
      recovery in striatal DA metabolites at eight weeks after MPTP administration
      compared to controls, suggesting that 14-3-3theta overexpression may help in the
      functional recovery of those dopaminergic neurons that survive. Conversely, we
      investigated whether disrupting 14-3-3 function in transgenic mice expressing the
      pan 14-3-3 inhibitor difopein exacerbates MPTP-induced toxicity. We found that
      difopein expression promoted dopaminergic cell loss in response to MPTP
      treatment. Together, these findings suggest that 14-3-3theta overexpression
      promotes recovery of DA metabolites whereas 14-3-3 inhibition exacerbates neuron
      loss in the MPTP mouse model of PD. 

PMID- 26314635
TI  - Differences in the use of vision and proprioception for postural control in
      autism spectrum disorder.
AB  - BACKGROUND: People with autism spectrum disorders (ASDs) also have poorer
      fundamental motor skills. The development of postural control underlies both
      social and motor skills. All three elements are facilitated by the active use of
      visual information. This study compares how adults with ASD and typically
      developed adults (TDAs) respond to a postural illusion induced using neck
      vibration. Adults with ASD unlike the TDA, were not expected to correct the
      illusion using vision. METHODS: The study used intermittent (15off, 5on)
      posterior neck vibration during 200 s of quiet stance to induce a postural
      illusion. In TDAs and only in the absence of vision this protocol induces a
      forward body lean. Participants (12 ASD, 20 TDA) undertook four conditions
      combining vibration and visual occlusion. RESULTS: As predicted, TDA were only
      affected by the postural illusion when vision was occluded (vibration condition:
      vision occluded (n=1) p=0.0001; vision available (n=3) p>0.2466). Adults with ASD
      were affected by the postural illusion regardless of the availability of vision
      (all conditions p<0.0007). CONCLUSIONS: Our findings indicated the adults with
      ASD did not use visual information to control standing posture. In light of
      existing evidence that vision-for-perception is processed typically in ASD, our
      findings support a specific deficit in vision-for-action. These findings may
      explain why individuals with ASD experience difficulties with both social and
      motor skills since both require vision-for-action. Further research needs to
      investigate the division of these visual learning pathways in order to provide
      more specific intervention opportunities in ASD.

PMID- 26314631
TI  - The keystone of Alzheimer pathogenesis might be sought in Abeta physiology.
AB  - For several years Amyloid-beta peptide (Abeta) has been considered the main
      pathogenetic factor of Alzheimer's disease (AD). According to the so called
      Amyloid Cascade Hypothesis the increase of Abeta triggers a series of events
      leading to synaptic dysfunction and memory loss as well as to the structural
      brain damage in the later stage of the disease. However, several evidences
      suggest that this hypothesis is not sufficient to explain AD pathogenesis,
      especially considering that most of the clinical trials aimed to decrease Abeta
      levels have been unsuccessful. Moreover, Abeta is physiologically produced in the
      healthy brain during neuronal activity and it is needed for synaptic plasticity
      and memory. Here we propose a model interpreting AD pathogenesis as an alteration
      of the negative feedback loop between Abeta and its physiological receptors,
      focusing on alpha7 nicotinic acetylcholine receptors (alpha7-nAchRs). According
      to this vision, when Abeta cannot exert its physiological function a negative
      feedback mechanism would induce a compensatory increase of its production leading
      to an abnormal accumulation that reduces alpha7-nAchR function, leading to
      synaptic dysfunction and memory loss. In this perspective, the indiscriminate
      Abeta removal might worsen neuronal homeostasis, causing a further impoverishment
      of learning and memory. Even if further studies are needed to better understand
      and validate these mechanisms, we believe that to deepen the role of Abeta in
      physiological conditions might represent the keystone to elucidate important
      aspects of AD pathogenesis. 

PMID- 26314632
TI  - Animal models of bipolar mania: The past, present and future.
AB  - Bipolar disorder (BD) is the sixth leading cause of disability in the world
      according to the World Health Organization and affects nearly six million (~2.5%
      of the population) adults in the United State alone each year. BD is primarily
      characterized by mood cycling of depressive (e.g., helplessness, reduced energy
      and activity, and anhedonia) and manic (e.g., increased energy and hyperactivity,
      reduced need for sleep, impulsivity, reduced anxiety and depression), episodes.
      The following review describes several animal models of bipolar mania with a
      focus on more recent findings using genetically modified mice, including several
      with the potential of investigating the mechanisms underlying 'mood' cycling (or
      behavioral switching in rodents). We discuss whether each of these models satisfy
      criteria of validity (i.e., face, predictive, and construct), while highlighting
      their strengths and limitations. Animal models are helping to address critical
      questions related to pathophysiology of bipolar mania, in an effort to more
      clearly define necessary targets of first-line medications, lithium and valproic
      acid, and to discover novel mechanisms with the hope of developing more effective
      therapeutics. Future studies will leverage new technologies and strategies for
      integrating animal and human data to reveal important insights into the etiology,
      pathophysiology, and treatment of BD. 

PMID- 26314638
TI  - Impact Is Everything.

PMID- 26314637
TI  - Do Shale Pore Throats Have a Threshold Diameter for Oil Storage?
AB  - In this work, a nanoporous template with a controllable channel diameter was used
      to simulate the oil storage ability of shale pore throats. On the basis of the
      wetting behaviours at the nanoscale solid-liquid interfaces, the seepage of oil
      in nano-channels of different diameters was examined to accurately and
      systematically determine the effect of the pore diameter on the oil storage
      capacity. The results indicated that the lower threshold for oil storage was a
      pore throat of 20 nm, under certain conditions. This proposed pore size threshold
      provides novel, evidence-based criteria for estimating the geological reserves,
      recoverable reserves and economically recoverable reserves of shale oil. This new
      understanding of shale oil processes could revolutionize the related industries. 

PMID- 26314636
TI  - Effects of BACE1 haploinsufficiency on APP processing and Abeta concentrations in
      male and female 5XFAD Alzheimer mice at different disease stages.
AB  - beta-Site APP-cleaving enzyme 1 (BACE1) initiates the generation of amyloid-beta
      (Abeta), thus representing a prime therapeutic target for Alzheimer's disease
      (AD). Previous work including ours has used BACE1 haploinsufficiency (BACE1(+/-);
      i.e., 50% reduction) as a therapeutic relevant model to evaluate the efficacy of
      partial beta-secretase inhibition. However, it is unclear whether the extent of
      Abeta reductions in amyloid precursor protein (APP) transgenic mice with BACE1(+/
      ) gene ablation may vary with sex or disease progression. Here, we compared the
      impacts of BACE1 haploinsufficiency on Abeta concentrations and APP processing in
      5XFAD Alzheimer mice (1) between males and females and (2) between different
      stages with moderate and robust Abeta accumulation. First, male and female 5XFAD
      mice at 6-7 months of age showed equivalent levels of Abeta, BACE1, full-length
      APP and its metabolites. BACE1 haploinsufficiency significantly lowered soluble
      Abeta oligomers, total Abeta42 levels and plaque burden in 5XFAD mouse brains
      irrespective of sex. Furthermore, there was no sex difference in reductions of
      beta-cleavage products of APP (C99 and sAPPbeta) found in BACE1(+/-).5XFAD mice
      relative to BACE1(+/+).5XFAD controls. Meanwhile, APP and sAPPalpha levels in
      BACE1(+/-).5XFAD mice were higher than those of 5XFAD controls regardless of sex.
      Based on these observations, we next combined male and female data to examine the
      effects of BACE1 haploinsufficiency in 5XFAD mice at 12-14 months of age, as
      compared with those in 6-7-month-old 5XFAD mice. Oligomeric Abeta and C99 levels
      were dramatically elevated in older 5XFAD mice. Although the beta-metabolites of
      APP were significantly reduced by BACE1 haploinsufficiency in both age groups,
      high levels of these toxic amyloidogenic fragments remained in 12-14-month-old
      BACE1(+/-).5XFAD mice. The present findings are consistent with our previous
      behavioral data showing that BACE1 haploinsufficiency rescues memory deficits in
      5XFAD mice irrespective of sex but only in the younger age group.

PMID- 26314639
TI  - Endovascular Treatment of Acute Ischemic Stroke: New Data, New Truth.

PMID- 26314641
TI  - JVIR Celebrates 25 Years of Innovation. Part 3: 2001-2005.

PMID- 26314640
TI  - Internal Iliac Artery Embolization for Benign Prostatic Hyperplasia? First Read
      the Fine Print.

PMID- 26314642
TI  - Superficial Femoral Artery Duplication.

PMID- 26314643
TI  - Endovenous Laser Ablation Can Safely and Successfully Treat Large-Diameter
      Saphenous Veins: A Posse ad Esse (from Possibility to Actuality).

PMID- 26314645
TI  - Abscess-Fistula Complexes: A Systematic Approach for Percutaneous Catheter
      Management.
AB  - PURPOSE: To describe a systematic catheter management approach for treatment of
      abscesses with enteric fistulae by abscess evacuation and selective fistula tract
      cannulation in a series of patients with postprocedural abscess-fistula
      complexes. MATERIALS AND METHODS: This single-center retrospective study included
      27 patients (17 male; mean age, 51.3 y) who underwent percutaneous drainage of
      postprocedural abscess-fistula complexes from January 2005 to September 2013.
      There were 15 low-output and 12 high-output fistulae. Intra-abdominal abscesses
      were evacuated by percutaneous drainage. Multiple catheters were used for
      collections with viscous fluid or size >= 6 cm in diameter. High-output fistulae
      and recurrent low-output fistulae had additional catheter cannulation of the
      enteric hole to facilitate the creation of a controlled enterocutaneous tract.
      There was no preexisting cutaneous tract before catheter insertion in 23
      fistulae. RESULTS: Abscess-fistula complex resolution occurred in 24 patients
      (88.9%). Of the 3 cases of failure, 2 patients required surgical repair of the
      fistula, and 1 patient died. Mean number of drainage procedures was 7.0, and mean
      catheter duration was 76.1 days. There was no significant difference in catheter
      duration of low-output and high-output abscess-fistula complexes (P = .34);
      however, high-output patients underwent significantly more procedures (9.1 vs
      6.1, P = .025). There were 15 fistulae that were cannulated (11 high-output and 4
      low-output fistulae). Cannulated abscess-fistula complexes had significantly
      longer catheter duration (102.5 d vs 53.2 d, P = .04) and underwent significantly
      more procedures (8.4 vs 5.4, P = .04). CONCLUSIONS: The catheter management
      strategy was successful in resolving most abscess-fistula complexes in this
      series.

PMID- 26314646
TI  - Percutaneous Extraction of Embolized Intracardiac Inferior Vena Cava Filter
      Struts Using Fused Intracardiac Ultrasound and Electroanatomic Mapping.
AB  - This report describes the percutaneous extraction of embolized intracardiac
      inferior vena cava (IVC) filter struts using fluoroscopy and fused intracardiac
      echocardiography and three-dimensional electroanatomic mapping. Six patients with
      indwelling IVC filters placed at outside institutions 5 months to 14 years
      previously presented with cross-sectional imaging of the chest demonstrating
      fractured IVC filter struts embolized to the myocardial free wall (four patients)
      or interventricular septum (two patients). All embolized filter struts were
      successfully retrieved, and open heart surgery was avoided. 

PMID- 26314647
TI  - Allergic Reaction following Implantation of a Nitinol Alloy Inferior Vena Cava
      Filter.
AB  - A 67-year-old woman developed severe pruritus after implantation of a retrievable
      nitinol inferior vena cava (IVC) filter (55.4% nickel and 44.6% titanium). The
      pruritus resolved only after filter retrieval. The patient's hypersensitivity to
      nickel was confirmed by a positive skin patch test substantiating a systemic
      allergic reaction to the implanted nitinol IVC filter. 

PMID- 26314648
TI  - Endovascular Retrieval of Surgical Sponge within Pulmonary Artery.

PMID- 26314649
TI  - Retroperitoneal Intranodal Contrast Agent Injection for Lymphangiographic Imaging
      of the Thoracic Duct in View of Percutaneous Intervention.

PMID- 26314650
TI  - Direct Cervical Puncture for Retrograde Thoracic Duct Embolization in a
      Postoperative Cervical Lymphatic Fistula.

PMID- 26314651
TI  - Use of the VASCADE Arterial Closure Device to Achieve Hemostasis after a Deep
      Venous Procedure.

PMID- 26314652
TI  - Use of StarClose Device under Ultrasound Guidance in Inadvertent Carotid Artery
      Puncture.

PMID- 26314653
TI  - Successful Occlusion of the Splenic Artery Using the Endoluminal Occlusion
      System.

PMID- 26314654
TI  - Intimo-Intimal Intussusception: A Rare Form of Common Carotid Artery Dissection.

PMID- 26314655
TI  - Shunt-Preserving Splenic Vein Embolization Using a Vascular Plug for Treatment of
      Hepatic Encephalopathy.

PMID- 26314656
TI  - Comments on "Evaluation of a Noise Reduction Imaging Technology in Iliac Digital
      Subtraction Angiography: Noninferior Clinical Image Quality with Lower Patient
      and Scatter Dose".

PMID- 26314657
TI  - Reply to: "Comments on "Evaluation of a Noise Reduction Imaging Technology in
      Iliac Digital Subtraction Angiography: Noninferior Clinical Image Quality with
      Lower Patient and Scatter Dose"".

PMID- 26314658
TI  - Sellar gangliocytoma with adrenocorticotropic and prolactin adenoma.
AB  - We report a case of a 60-year-old man who presented with weight gain, headaches,
      dizziness, erectile dysfunction and decreased libido. He was found to have
      elevated adrenocorticotropic hormone (ACTH) and prolactin serum levels. The
      imaging studies revealed a 1.4 cm sella/suprasellar mass which was compressing
      the optic chiasm. Histologic slides of the lesion showed a pituitary adenoma,
      marked by a proliferation of biphenotypic appearing cells, associated with a
      gangliocytoma, and marked by a proliferation of atypical appearing neuronal cells
      arranged against a glial-appearing background. Pituitary adenoma-gangliocytomas
      are benign combination tumors that rarely occur in the sellar region. Adenomas in
      this setting are sometimes functional, and rare patients with mixed adenomas
      (adenomas secreting more than one hormone) have been reported. To our knowledge,
      there has been only one other report of a combined ACTH and prolactin-producing
      adenoma with gangliocytoma, reported in a patient who also had acromegaly. In our
      patient, the immunohistochemical stains demonstrated that the bulk of the adenoma
      cells stained with prolactin antibody, and scattered clusters of cells within the
      adenoma stained positively for ACTH. The adenoma did not stain with antibodies to
      any of the other anterior pituitary hormones. Postoperatively, the elevated
      prolactin and ACTH levels returned to normal levels and there was no evidence of
      residual tumor. Adequate sampling and immunohistochemistry are important in
      rendering a correct diagnosis and in identifying the hormone status of mixed
      adenoma-gangliocytomas.

PMID- 26314659
TI  - Considerations and complications after Bells' palsy.
AB  - We present a retrospective, observational study of all patients diagnosed with
      Bells' palsy (BP) at the Central District of Clalit Health Services from 2003
      through to 2012. BP is associated with several complications. We evaluated
      clinical characteristics including the number of patient visits to general
      physicians (GP), otolaryngologists, ophthalmologists and neurologists,
      medications prescribed in the acute phase of BP (steroids and antiviral agents),
      and the ophthalmic diagnoses. A total of 4463 patients with the diagnosis of BP
      were included. The incidence per 100,000/year was 87.0, and it increased with
      age. Patients had significantly more visits to all specialists at 6 months after
      the BP event. Steroid treatment was prescribed to 50.4% of the patients and
      antiviral agents to 65.5%. Both treatments were associated with older patient age
      and female sex. The rate of post BP lagophthalmos and keratitis was 3.45% and
      0.63% at 1-3 months, respectively, and both were more likely to develop in older
      patients. Steroid and/or antiviral treatments were not associated with a decrease
      in ophthalmic complications. BP may cause ophthalmic complications at a low rate,
      which are associated with older age. Steroids and antiviral agents appeared to
      have no effect on ophthalmic complications.

PMID- 26314660
TI  - Expanding the spectrum of subacute diencephalic angioencephalopathy.
AB  - We present a patient with subacute diencephalic angioencephalopathy (SDAE), a
      poorly understood syndrome of progressive confusion, disorientation, and dementia
      that rapidly deteriorates to severe encephalopathy and death. This is the seventh
      and most thoroughly investigated report of this exceedingly rare diagnosis to
      date, and we present the first evidence of a potential sentinel syndrome that may
      allow for earlier diagnosis and therapeutic intervention. We also review the
      relevant literature, and highlight new evidence that suggests that SDAE and the
      related disorder, subacute brainstem angioencephalopathy (SBAE), represent severe
      and terminal variants of posterior reversible encephalopathy syndrome (PRES).
      Taken together, we suggest a new understanding of SDAE/SBAE and PRES as a
      spectrum of hypertension-associated non-inflammatory vascular encephalopathies
      that are mediated by a loss of venous autoregulation, marked by cytotoxic edema,
      and that ultimately produce subacute-to-acute diencephalic, brainstem, and
      posterior fossa injuries with devastating neurologic consequences. 

PMID- 26314661
TI  - Clinical characteristics and post-surgical outcomes of focal cortical dysplasia
      subtypes.
AB  - We retrospectively studied 105 patients with a focal cortical dysplasia (FCD)
      diagnosed on pathological examination, and investigated the long term
      postoperative seizure outcomes, different clinical characteristics of the three
      FCD subtypes, particularly type I and II, and surgical outcomes for each group.
      FCD is a common cause of drug-resistant epilepsy, which is divided into three
      different subtypes according to its involvement at different stages of brain
      development. Each of these groups may have different characteristics and may even
      have different surgical outcomes. After treatment, 55% of patients were
      completely seizure-free, with two significant predictive variables for poorer
      outcomes: focal MRI findings and electrode implantation. FCD type I had
      relatively poor surgical outcomes compared to FCD type II and type IIIa. Compared
      with FCD type I, type II, particularly IIb, had a higher frequency of seizure
      attacks, predominantly located in the extratemporal lobes, and was more readily
      detected and diagnosed via focal lesions on MRI and localized
      electroencephalogram abnormalities. FCD type II patients seem to show better
      surgical outcomes than FCD type I, but the difference was not significant. Larger
      cohort studies are needed for further evaluation of the seizure outcomes of
      different FCD subtypes. 

PMID- 26314662
TI  - Long-term Results of an Accelerated Corneal Cross-linking Protocol (18 mW/cm2)
      for the Treatment of Progressive Keratoconus.
AB  - PURPOSE: To compare the long-term outcomes of accelerated and standard corneal
      cross-linking protocols in the treatment of progressive keratoconus. DESIGN:
      Prospective randomized clinical trial. METHODS: Thirty-one eyes with keratoconus
      were treated with an accelerated protocol (18 mW/cm(2), 5 min) and all
      contralateral eyes were treated with the standard method (3 mW/cm(2), 30 min)
      using the same overall fluence of 5.4 J/cm(2). RESULTS: At 18 months after the
      procedure, the standard group showed significant improvement in spherical
      equivalent (P < .05), K-readings (P < .05), Q value (P < .05), index of surface
      variance (P < .05), and keratoconus index (P = .008) and decline in central
      corneal thickness (P < .05), but no significant change in visual acuity, corneal
      hysteresis, corneal resistance factor, P2 area, or endothelial cell density. In
      the accelerated group, central corneal thickness was the only parameter with
      statistically significant change. However, neither of these parameters showed
      significant differences between the standard and the 18 mW/cm(2) accelerated
      protocol, except K-reading (P = .059) and index surface variance (P = .034).
      CONCLUSION: An accelerated cross-linking protocol, using 18 mW/cm(2) for 5
      minutes, shows a comparable outcome and safety profile when compared to the
      standard protocol, but better corneal flattening is achieved with the standard
      method than the accelerated method. Overall, both methods stop the disease
      progression similarly. This study will continue to examine more long-term
      results.

PMID- 26314663
TI  - Morphology and Vascular Layers of the Choroid in Stargardt Disease Analyzed Using
      Spectral-Domain Optical Coherence Tomography.
AB  - PURPOSE: To analyze total thickness, morphology and individual vascular layers of
      the choroid in eyes with Stargardt disease using spectral-domain optical
      coherence tomography (SD OCT). DESIGN: Cross-sectional retrospective review.
      METHODS: Twenty-eight patients with Stargardt disease (53 eyes) with a mean age
      of 46 (15-79) years and 30 healthy subjects (30 eyes) with a mean age of 49 (22
      79) years who underwent 1-line raster scanning with SD OCT were identified.
      Diagnosis of Stargardt disease was based on ophthalmic history and complete
      ophthalmic evaluation. The healthy subjects had best-corrected visual acuity of
      20/20 or better with no chorioretinal pathology. Two independent raters assessed
      the total thickness, morphology, and the individual vascular layers of the
      choroid. RESULTS: The choroid was irregularly shaped in 26 of 41 eyes (64%) with
      Stargardt disease when compared to 0 of 30 healthy eyes (0%). Mean subfoveal
      total choroidal thickness and mean subfoveal large choroidal vessel layer
      thickness were significantly reduced in eyes with Stargardt disease when compared
      to healthy eyes (272.8 +/- 32.8 MUm vs 225.4 +/- 69.9 MUm; P = .03 and 219.5 +/-
      30.6 vs169.2 +/- 70.1; P = .04, respectively). The maximal choroidal thickness
      was subfoveal in 9 of 41 eyes (22%), focal choroidal thinning was observed in 21
      of 41 eyes (51%), and attenuation of large choroidal vessel layer was observed in
      8 of 41 eyes (20%) with Stargardt disease. There was no association of the best
      corrected visual acuity with any choroidal morphologic feature, except that it
      was better by a mean of 0.61 +/- 0.21 in eyes that had preservation of large
      choroidal vessel layer (33 of 41, 80%) when compared to those that had
      attenuation of large choroidal vessel layer (P = .007). CONCLUSION: This study
      shows alterations in the total thickness, morphology, and the individual vascular
      layers of the choroid in eyes with Stargardt disease on SD OCT. These findings
      may potentially contribute to the clinical staging and monitoring of Stargardt
      disease.

PMID- 26314664
TI  - Efficient capture of natural history data reveals prey conservatism of cryptic
      termite predators.
AB  - Stenophagy, specialization of a clade on a narrow range of taxa, has not been
      well studied in speciose clades of predators, principally due to the difficulty
      of obtaining adequate natural history data. The pantropical Salyavatinae
      (Hemiptera: Reduviidae; 17 genera, 107 species) contains members with enigmatic
      morphology and specialized behavior for feeding on termites. All Salyavatinae are
      suspected specialist termite predators; however, existing observations are
      limited to seven species. Prior analyses indicate that Salyavatinae may be
      paraphyletic with respect to another subfamily, Sphaeridopinae, also hypothesized
      to feed on termites. A molecular phylogeny of these putative termite assassins is
      here constructed using seven loci from 28 species in nine genera and is used in a
      dating analysis to shed light on the timing of Neotropical colonization by this
      primarily Old World clade. DNA extracted from gut contents of 50 individuals was
      assayed using PCR with prey-specific primers.Molecular assays, along with recent
      photographs and observations, provide substantial evidence that this clade feeds
      specifically upon termites, documenting 28 new individual associations. Our
      phylogeny supports a sister group relationship of the Neotropical genus Salyavata
      with Sphaeridopinae. Termite association data combined with our phylogeny provide
      evidence of previously unknown prey conservatism among clades of one of the most
      diverse groups of specialist termite predators.

PMID- 26314665
TI  - Diagnosis of Helicobacter pylori Infection in the Proton Pump Inhibitor Era.
AB  - Proton pump inhibitors (PPI) are a major cause of false-negative Helicobacter
      pylori test results. Detecting PPI use and stopping it 2 weeks before testing is
      the preferred approach to improve the reliability of H pylori diagnostic tests.
      Immunoblot and molecular methods may be useful for the detection of H pylori
      infection in difficult cases. When conventional tests are negative and
      eradication is strongly indicated, empirical H pylori treatment should be
      considered. In this article, an updated critical review of the usefulness of the
      various invasive and noninvasive tests in the context of extensive PPI use is
      provided. 

PMID- 26314666
TI  - Practical Aspects in Choosing a Helicobacter pylori Therapy.
AB  - Cure rates greater than 90%-95% should be expected with an antimicrobial therapy
      for Helicobacter pylori infection. Standard triple therapy does not guarantee
      these efficacy rates in most settings worldwide anymore. The choice of
      eradication regimen should be dictated by factors that can predict the outcome:
      (1) H. pylori susceptibility; (2) patients' history of prior antibiotic therapy;
      and (3) local data, either resistance patterns or clinical success. Currently,
      the preferred first-line choices are 14-day bismuth quadruple and 14-day non
      bismuth quadruple concomitant therapy. Bismuth quadruple (if not used
      previously), fluoroquinolone-, furazolidone- and rifabutin-containing regimens
      might be effective rescue treatments. 

PMID- 26314668
TI  - Is There a Role for Probiotics in Helicobacter pylori Therapy?
AB  - The role of probiotics in Helicobacter pylori therapy remains unclear.
      Lactobacilli can be shown to inhibit H pylori in vitro. Some strains of
      Lactobacilli may exert specific antimicrobial effects. There is no strong
      evidence of a benefit on eradication rate when probiotics are added to a regimen.
      Despite promising results obtained using compounds of L reuteri and S boulardii,
      high-quality trials are needed to define the role of probiotics as adjuvant
      therapy. Variables that remain to be studied with L reuteri, currently the most
      promising strain, include dosage, frequency of administration, administration in
      relation to meals, and duration of therapy.

PMID- 26314669
TI  - Molecular Approaches to Identify Helicobacter pylori Antimicrobial Resistance.
AB  - Antimicrobial susceptibility testing is needed to adapt Helicobacter pylori
      treatment to obtain the best results. Beside the standard phenotypic methods,
      molecular methods are increasingly used. The value of these molecular tests is
      that they are quick, independent of the transport conditions, easy to
      standardize, and commercial kits are available. In this article, these methods
      are reviewed, focusing on the determination of H pylori resistance to macrolides
      and fluoroquinolones, and mentioning also the methods used for tetracycline and
      rifampin. 

PMID- 26314670
TI  - When Is Endoscopic Follow-up Appropriate After Helicobacter pylori Eradication
      Therapy?
AB  - The effect of Helicobacter pylori eradication treatment needs confirmation in
      patients with persistent symptoms and in those with complicated peptic ulcer.
      Endoscopic surveillance after eradication is needed in patients with advanced
      premalignant gastric lesions, previous early gastric cancer, gastric MALT
      lymphoma, and in those with a hereditary gastric cancer risk. 

PMID- 26314667
TI  - How to Effectively Use Bismuth Quadruple Therapy: The Good, the Bad, and the
      Ugly.
AB  - Bismuth triple therapy was the first effective Helicobacter pylori eradication
      therapy. The addition of a proton pump inhibitor helped overcome metronidazole
      resistance. Its primary indication is penicillin allergy or when clarithromycin
      and metronidazole resistance are both common. Resistance to the primary first
      line therapy have centered on complexity and difficulties with compliance.
      Understanding regional differences in effectiveness remains unexplained because
      of the lack of studies including susceptibility testing and adherence data. We
      discuss regimen variations including substitutions of doxycycline, amoxicillin,
      and twice a day therapy and provide suggestions regarding what is needed to
      rationally and effectively use bismuth quadruple therapy. 

PMID- 26314671
TI  - Gastric Cancer Risk in Patients with Helicobacter pylori Infection and Following
      Its Eradication.
AB  - As Helicobacter pylori is a first-class carcinogen, eradication of the infection
      would be expected to be a beneficial measure for the (primary) prevention of
      gastric cancer. Given the natural history of gastric cancer, it is plausible that
      eradication before gastric atrophy sets in offers the best chance for cancer risk
      reduction. The beneficial effects of eradication may, nevertheless, still be
      achievable in more advanced disease. The reversibility of inflammatory lesions
      has been supported by undeniable evidence; the regression of mucosal
      atrophy/metaplasia has also been confirmed by several recent histologic studies. 

PMID- 26314672
TI  - Molecular Pathogenesis of Helicobacter pylori-Related Gastric Cancer.
AB  - Helicobacter pylori infection plays a crucial role in gastric carcinogenesis. H
      pylori exerts oncogenic effects on gastric mucosa through complex interaction
      between bacterial virulence factors and host inflammatory responses. On the other
      hand, gastric cancer develops via stepwise accumulation of genetic and epigenetic
      alterations in H pylori-infected gastric mucosa. Recent comprehensive analyses of
      gastric cancer genomes indicate a multistep process of genetic alterations as
      well as possible molecular mechanisms of gastric carcinogenesis. Both genetic
      processes of gastric cancer development and molecular oncogenic pathways related
      to H pylori infection are important to completely understand the pathogenesis of
      H pylori-related gastric cancer. 

PMID- 26314673
TI  - Helicobacter pylori Eradication to Eliminate Gastric Cancer: The Japanese
      Strategy.
AB  - Helicobacter pylori eradication therapy for chronic gastritis achieved world
      first coverage by the Japanese national health insurance scheme in 2013, making a
      dramatic decrease of gastric cancer-related deaths more realistic. Combining H
      pylori eradication therapy with endoscopic surveillance can prevent the
      development of gastric cancer. Even if it develops, most patients are likely to
      be diagnosed at an early stage, possibly resulting in fewer gastric cancer
      deaths. Success with the elimination of gastric cancer in Japan could lead other
      countries with a high incidence to consider a similar strategy, suggesting the
      potential for elimination of gastric cancer around the world. 

PMID- 26314674
TI  - Treatment Strategy for Gastric Mucosa-Associated Lymphoid Tissue Lymphoma.
AB  - Recent trends and current knowledge on the diagnosis and treatment strategy for
      gastric mucosa-associated lymphoid tissue (MALT) lymphoma are reviewed.
      Helicobacter pylori infection plays the causative role in the pathogenesis, and H
      pylori eradication is the first-line treatment of this disease, which leads to
      complete remission in 60% to 90% of cases. A Japanese multicenter study confirmed
      that the long-term outcome of gastric MALT lymphoma after H pylori eradication is
      excellent. Treatment strategies for patients not responding to H pylori
      eradication including "watch and wait" strategy, radiotherapy, chemotherapy,
      rituximab immunotherapy, and combination of these should be tailored in
      consideration of the disease extent in each patient. 

PMID- 26314675
TI  - Rationale for a Helicobacter pylori Test and Treatment Strategy in
      Gastroesophageal Reflux Disease.
AB  - Conflicting data have been published on the effect of long-term proton pump
      inhibitor therapy on the gastric mucosa in Helicobacter pylori-infected subjects.
      In this article, the available data are reviewed and a rationale is offered for
      why infected patients who are about to commence long-term proton pump inhibitor
      therapy should be offered eradication therapy. 

PMID- 26314676
TI  - Screening to Identify and Eradicate Helicobacter pylori Infection in Teenagers in
      Japan.
AB  - The purpose of this study was to elucidate the prevalence and effect of
      Helicobacter pylori infection in Japanese teenagers. The study subjects were
      students ages 16 to 17 from one high school studied between 2007 and 2013.
      Students who tested positive on this screening examination underwent
      esophagogastroduodenoscopy and biopsy samples to determine their H pylori status
      using culture and histology. Cure of H pylori infections was determined by urea
      breath test. The low rate of prevalence of H pylori infection in present Japanese
      teenagers makes it possible and cost effective to perform examinations and carry
      out treatment of this infection in nationwide health screenings of high school
      students. 

PMID- 26314677
TI  - Current Status and Prospects for a Helicobacter pylori Vaccine.
AB  - Helicobacter pylori infection contributes to a variety of gastric diseases. H
      pylori-associated gastric cancer is diagnosed in advanced stages, and a vaccine
      against H pylori is desirable in parts of the world where gastric cancer remains
      a common form of cancer. Some of the strategies of vaccine development used in
      animals have been tested in several phase 3 clinical trials; these trials have
      been largely unsuccessful, although H pylori-specific immune responses have been
      induced. New insights into promoting immunity and overcoming the
      immunosuppressive nature of H pylori infection are required to improve the
      efficacy of an H pylori vaccine. 

PMID- 26314679
TI  - Helicobacter pylori: New Thoughts and Practices.

PMID- 26314680
TI  - Snapping mechanical metamaterials under tension.
AB  - A snapping mechanical metamaterial is designed, which exhibits a sequential snap
      through behavior under tension. The tensile response of this mechanical
      metamaterial can be altered by tuning the architecture of the snapping segments
      to achieve a range of nonlinear mechanical responses, including monotonic, S
      shaped, plateau, and non-monotonic snap-through behavior. 

PMID- 26314681
TI  - Lyotropic La-containing lamellar liquid crystals: phase behaviour, thermal and
      structural properties.
AB  - This paper provides the results of POM, DSC and XRPD methods characterizing the
      liquid crystalline behaviour, thermal properties and structural parameters of
      lyotropic systems based on a nonionic surfactant and lanthanum nitrate (La(3+)).
      The systems based on tetraethylene glycol monododecyl ether (C12EO4) and
      lanthanum nitrate have been demonstrated to form a lamellar phase. The
      concentration and temperature ranges of the existence of mesophases as well as
      thermodynamic parameters of phase transitions have been estimated. The structural
      parameters of the lamellar phase of the C12EO4/La(3+)/water systems have been
      determined using X-ray diffraction. The model of molecular packing in lamellar
      lanthanide-containing lyotropic mesophases was proposed for the observed patterns
      of structural parameters obtained at various water contents. NMR (1)H with a
      pulsed magnetic field gradient has been used to characterize molecular motions in
      the C12EO4/La(3+)/H2O systems with different water contents. 

PMID- 26314682
TI  - Deciphering the biochemistry and identifying biomarkers to multiple sclerosis.
AB  - Multiple sclerosis is an idiopathic demyelinating disease of the CNS. Despite
      being extensively studied during the last decades, many molecular aspects of the
      disease are still to be elucidated. Moreover, biomarkers for treatment and early
      diagnosis are major issues to be tackled. In this edition of Kroksveen et al.
      (Proteomics 2015, 15, 3361-3369) present biomarker candidates for the early
      detection of multiple sclerosis. Despite the need for validation in larger sets
      of samples, this dataset contributes to resolve open questions associated to
      multiple sclerosis.

PMID- 26314683
TI  - Sensitive Fibre-Based Thermoluminescence Detectors for High Resolution In-Vivo
      Dosimetry.
AB  - With interest in the potential of optical fibres as the basis of next-generation
      thermoluminescence dosimeters (TLDs), the development of suitable forms of
      material and their fabrication has become a fast-growing endeavour. Present study
      focuses on three types of Ge-doped optical fibres with different structural
      arrangements and/or shapes, namely conventional cylindrical fibre, capillary
      fibre, and flat fibre, all fabricated using the same optical fibre preform. For
      doses from 0.5 to 8 Gy, obtained at electron and photon energies, standard
      thermoluminescence (TL) characteristics of the optical fibres have been the
      subject of detailed investigation. The results show that in collapsing the
      capillary fibre into a flat shape, the TL yield is increased by a factor of 5.5,
      the yield being also some 3.2 times greater than that of the conventional
      cylindrical fibre fabricated from the same perform. This suggests a means of
      production of suitably sensitive TLD for in-vivo dosimeter applications.
      Addressing the associated defects generating luminescence from each of the
      optical fibres, the study encompasses analysis of the TL glow curves, with
      computerized glow curve deconvolution (CGCD) and 2(nd) order kinetics. 

PMID- 26314684
TI  - Genome-wide Association Study of Autism Spectrum Disorder in the East Asian
      Populations.
AB  - Autism spectrum disorder is a heterogeneous neurodevelopmental disorder with
      strong genetic basis. To identify common genetic variations conferring the risk
      of ASD, we performed a two-stage genome-wide association study using ASD family
      and healthy control samples obtained from East Asian populations. A total of 166
      ASD families (n = 500) and 642 healthy controls from the Japanese population were
      used as the discovery cohort. Approximately 900,000 single nucleotide
      polymorphisms (SNPs) were genotyped using Affymetrix Genome-Wide Human SNP array
      6.0 chips. In the replication stage, 205 Japanese ASD cases and 184 healthy
      controls, as well as 418 Chinese Han trios (n = 1,254), were genotyped by TaqMan
      platform. Case-control analysis, family based association test, and
      transmission/disequilibrium test (TDT) were then conducted to test the
      association. In the discovery stage, significant associations were suggested for
      14 loci, including 5 known ASD candidate genes: GPC6, JARID2, YTHDC2, CNTN4, and
      CSMD1. In addition, significant associations were identified for several novel
      genes with intriguing functions, such as JPH3, PTPRD, CUX1, and RIT2. After a
      meta-analysis combining the Japanese replication samples, the strongest signal
      was found at rs16976358 (P = 6.04 * 10(-7)), which is located near the RIT2 gene.
      In summary, our results provide independent support to known ASD candidate genes
      and highlight a number of novel genes warranted to be further investigated in a
      larger sample set in an effort to improve our understanding of the genetic basis
      of ASD.

PMID- 26314685
TI  - Mitochondrial disorders with cardiac dysfunction: an under-reported aetiology
      with phenotypic heterogeneity.

PMID- 26314686
TI  - Approach to family screening in arrhythmogenic right ventricular
      dysplasia/cardiomyopathy.
AB  - AIMS: A combination of variable expression, age-related penetrance, and
      unpredictable arrhythmic events complicates management of relatives of
      arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) patients. We
      aimed to (i) determine predictors of ARVD/C diagnosis and (ii) optimize
      arrhythmic risk stratification among first-degree relatives of ARVD/C patients.
      METHODS AND RESULTS: Detailed phenotypic and outcome data of 274 first-degree
      relatives (46% male; 36.5 +/- 18.9 years) of 138 ARVD/C probands were obtained.
      Ninety-six (35%) relatives were diagnosed with ARVD/C according to 2010 Task
      Force Criteria (TFC). Siblings had a three-fold-increased risk of ARVD/C
      diagnosis compared with parents and children (odds ratio 3.11, P < 0.001).
      Multivariable logistic regression identified symptoms (P < 0.001), being a
      sibling (P < 0.001), the presence of a pathogenic mutation (P < 0.001), and
      female sex (P = 0.010) as predictors of ARVD/C diagnosis. During 6.7 +/- 3.8
      years of follow-up, 21 (8%) relatives experienced a sustained ventricular
      arrhythmia (cycle length 271 +/- 48 ms). While being a sibling was a predictor of
      ARVD/C diagnosis, neither relatedness to the proband (P = 0.185) nor malignant
      family history (P = 0.347) was significantly associated with arrhythmic events.
      Meeting TFC independent of family history criteria had higher prognostic value
      for arrhythmic events than conventional 2010 TFC, which include family history
      [area under the receiver operating characteristic curve 0.95 (95% CI 0.93-0.97)
      vs. 0.85 (95% CI 0.82-0.88), P < 0.001]. CONCLUSION: One-third of first-degree
      relatives develop manifest ARVD/C. Siblings have highest risk of disease, even
      after correcting for age and sex. Fulfilment of TFC independent of family history
      is superior to conventional TFC for arrhythmic risk stratification of relatives.

PMID- 26314687
TI  - Depression requiring anti-depressant drug therapy in adult congenital heart
      disease: prevalence, risk factors, and prognostic value.
AB  - BACKGROUND: Depression is prevalent in adults with congenital heart disease
      (ACHD), but limited data on the frequency of anti-depressant drug (ADD) therapy
      and its impact on outcome are available. METHODS AND RESULTS: We identified all
      ACHD patients treated with ADDs between 2000 and 2011 at our centre. Of 6162
      patients under follow-up, 204 (3.3%) patients were on ADD therapy. The majority
      of patients were treated with selective serotonin-reuptake inhibitors (67.4%),
      while only 17.0% of patients received tricyclic anti-depressants. Twice as many
      female patients used ADDs compared with males (4.4 vs. 2.2%, P < 0.0001). The
      percentage of patients on ADDs increased with disease complexity (P < 0.0001) and
      patient age (P < 0.0001). Over a median follow-up of 11.1 years, 507 (8.2%)
      patients died. After propensity score matching, ADD use was found to be
      significantly associated with worse outcome in male ACHD patients [hazard ratio
      1.44 (95% confidence interval 1.17-1.84)]. There was no evidence that this excess
      mortality was directly related to ADD therapy, QT-prolongation, or malignant
      arrhythmias. However, males taking ADDs were also more likely to miss scheduled
      follow-up appointments compared with untreated counterparts, while no such
      difference in clinic attendance was seen in females. CONCLUSIONS: The use of ADD
      therapy in ACHD relates to gender, age, and disease complexity. Although, twice
      as many female patients were on ADDs, it were their male counterparts, who were
      at increased mortality risk on therapy. Furthermore, males on ADDs had worse
      adherence to scheduled appointments suggesting the need for special medical
      attention and possibly psychosocial intervention for this group of patients.

PMID- 26314689
TI  - An aptamer targeting shared tumor-specific peptide antigen of MAGE-A3 in multiple
      cancers.
AB  - A DNA aptamer was identified against the shared tumor-specific MAGE-A3111-125
      peptide antigen. The dissociation constant between the aptamer and the peptide
      was measured at 57 nM. Binding of the aptamer to seven types of cancer cells,
      melanoma, breast, colorectal, liver, lung, pancreas and oral cancer, was
      confirmed with flow cytometry and fluorescence imaging. Cy3-conjugated aptamers
      signals were specifically localized to the surface of those cancer cells. The
      results indicate that the DNA aptamer against the shared tumor-specific MAGE-A3
      peptide can be used in cancer cell targeting and has the potential for developing
      into new modalities for the diagnosis of multiple cancers. 

PMID- 26314688
TI  - Comparison of vascular closure devices for access site closure after transfemoral
      aortic valve implantation.
AB  - BACKGROUND: The majority of transcatheter aortic valve implantation (TAVI)
      procedures are currently performed by percutaneous transfemoral approach. The
      potential contribution of the type of vascular closure device to the incidence of
      vascular complications is not clear. AIM: To compare the efficacy of a Prostar XL
      vs. Perclose ProGlide-based vascular closure strategy. METHODS: The ClOsure
      device iN TRansfemoral aOrtic vaLve implantation (CONTROL) multi-center study
      included 3138 consecutive percutaneous transfemoral TAVI patients, categorized
      according to vascular closure strategy: Prostar XL- (Prostar group) vs. Perclose
      ProGlide-based vascular closure strategy (ProGlide group). Propensity-score
      matching was used to assemble a cohort of patients with similar baseline
      characteristics. RESULTS: Propensity matching identified 944 well-matched
      patients (472 patient pairs). Composite primary end point of major vascular
      complications or in-hospital mortality occurred more frequently in Prostar group
      when compared with ProGlide group (9.5 vs. 5.1%, P = 0.016), and was driven by
      higher rates of major vascular complication (7.4 vs. 1.9%, P < 0.001) in the
      Prostar group. However, in-hospital mortality was similar between groups (4.9 vs.
      3.5%, P = 0.2). Femoral artery stenosis occurred less frequently in the Prostar
      group (3.4 vs. 0.5%, P = 0.004), but overall, Prostar use was associated with
      higher rates of major bleeding (16.7 vs. 3.2%, P < 0.001), acute kidney injury
      (17.6 vs. 4.4%, P < 0.001) and with longer hospital stay (median 6 vs. 5 days, P
      = 0.007). CONCLUSIONS: Prostar XL-based vascular closure in transfemoral TAVI
      procedures is associated with higher major vascular complication rates when
      compared with ProGlide; however, in-hospital mortality is similar with both
      devices.

PMID- 26314690
TI  - Experimental evidence for a time-integrated effect of productivity on diversity.
AB  - The time-area-productivity hypothesis is a proposed explanation for global
      biodiversity gradients. It predicts that a bioregion's modern diversity is the
      product of its area and productivity, integrated over evolutionary time. I
      performed the first experimental test of the time-area-productivity hypothesis
      using a model system for adaptive radiation - the bacterium Pseudomonas
      fluorescens SBW25. I initiated hundreds of independent radiations under culture
      conditions spanning a variety of productivities, spatial extents and temporal
      extents. Time-integrated productivity was the single best predictor of extant
      phenotypic diversity and richness. In contrast, 'snapshots' of modern
      environmental variables at the time of sampling were less useful predictors of
      diversity patterns. These results were best explained by marked variation in
      population growth parameters under different productivity treatments and the long
      periods over which standing diversity could persist in unproductive habitats.
      These findings provide the first experimental support for time-integrated
      productivity as a putative driver of regional biodiversity patterns.

PMID- 26314691
TI  - Median raphe stimulation-induced motor inhibition concurrent with suppression of
      type 1 and type 2 hippocampal theta.
AB  - This study investigated behavioral, anatomical and electrophysiological effects
      produced by electrical stimulation of posterior hypothalamic (PH) or median raphe
      (MR) nuclei, independently and during combined stimulation of both PH and MR.
      These three stimulation conditions were applied during spontaneous behavior in an
      open field and during PH stimulation-induced wheel running, while simultaneously
      recording hippocampal (HPC) field activity. An additional objective was to
      determine the effects of MR stimulation on Type 1 movement related theta and Type
      2 sensory processing related theta. To achieve the latter, when behavioral
      studies were completed we studied the same rats under urethane anesthesia and
      then during urethane anesthesia with the addition of atropine sulfate (ATSO4).
      Here we demonstrated that electrical stimulation of a localized region of the MR
      nucleus resulted in a profound inhibition of both spontaneously occurring theta
      related motor behaviors and the theta related motor behaviors induced by
      electrical stimulation of the PH nucleus. Furthermore, this motor inhibition
      occurred concurrently with strong suppression of hippocampal theta field
      oscillations in the freely moving rat, a condition where the theta recorded is
      Type 2 sensory processing theta occurring coincidently with Type 1 movement
      related theta (Bland, 1986). Our results indicate that motor inhibition resulted
      from stimulation of neurons located in the mid central region of the MR, while
      stimulation in adjacent regions produced variable responses, including movements
      and theta activity. The present study provided evidence that the pharmacological
      basis of the suppression of Type 2 sensory processing HPC theta was cholinergic.
      However, MR inhibition of PH-induced wheel running was not affected by
      cholinergic blockade, which blocks Type 2 theta, indicating that MR stimulation
      induced motor inhibition also requires the suppression of Type 1 theta.

PMID- 26314692
TI  - Tumor-Associated Macrophages Associate with Cerebrospinal Fluid Interleukin-10
      and Survival in Primary Central Nervous System Lymphoma (PCNSL).
AB  - Increased tumor-associated macrophages (TAMs) have been reported to be associated
      with poor prognosis in various tumors; however, the importance of TAMs in primary
      central nervous system lymphoma (PCNSL) has not been clarified. In 47 patients
      with PCNSL who were treated with high-dose methotrexate (MTX) and radiotherapy,
      the relationships between the infiltration levels of TAMs and the
      clinicopathological parameters were analyzed. Univariate analysis of the Cox
      proportional hazards model using continuous scales revealed that increased CD68
      positive (+) TAMs was significantly associated with inferior progression-free
      survival (PFS) (P = 0.04), and trends were observed for the increased CD163(+) 
      TAMs and having shorter PFS (P = 0.05). However, increased TAMs were not
      associated with overall survival. Because TAMs are known to produce various
      cytokines, we examined the relationships between cerebrospinal fluid (CSF)
      cytokines and TAMs. CSF interleukin-6 (IL-6) and soluble IL-2 receptor were not
      correlated with the infiltration rate of TAMs; however, CSF IL-10 level was
      correlated with infiltration levels of CD68 and CD163(+)  TAMs. We also confirmed
      the expression of IL-10 in CD68(+)  and CD163(+)  TAMs by double immunostaining
      analysis. Our results indicate that a high level of IL-10 in CSF may be
      positively associated with the infiltration level of TAMs in PCNSLs.

PMID- 26314693
TI  - Brief in Person Interventions for Adolescents and Young Adults Following Alcohol
      Related Events in Emergency Care: A Systematic Review and European Evidence
      Synthesis.
AB  - BACKGROUND: Increasing numbers of youth in need of emergency medical treatment
      following alcohol intoxication have been a major public health concern in Europe
      in recent years. Brief interventions (BIs) in the emergency department (ED) could
      prevent future risky drinking. However, effectiveness and feasibility of this
      approach are currently unclear. METHOD: A systematic literature search on
      controlled trials including participants aged 12-25 years treated in an ED
      following an alcohol-related event was conducted. Additionally, a grey literature
      search was conducted to support findings from the systematic review with evidence
      from practice projects and uncontrolled trials. Data on effectiveness,
      acceptance, implementation and reach were extracted. RESULTS: Seven randomised
      controlled trials (RCT), 6 practice projects, 1 non-randomised pilot study and 1
      observational study were identified. Six RCTs found reductions of alcohol use for
      all participants. Four RCTs found effects on alcohol consumption, alcohol-related
      risk-behaviour or referral to treatment. Participation and referral rates varied
      strongly, whereas data on acceptance and implementation were rarely assessed.
      CONCLUSION: Heterogeneity of study designs and effects limit conclusions on
      effectiveness of BIs for young ED patients following an alcohol-related event.
      However, the number of practice projects in Europe indicates a need perceived by
      practitioners to address this population.

PMID- 26314694
TI  - Rounding, work intensification and new public management.
AB  - In this study, we argue that contemporary nursing care has been overtaken by new
      public management strategies aimed at curtailing budgets in the public hospital
      sector in Australia. Drawing on qualitative interviews with 15 nurses from one
      public acute hospital with supporting documentary evidence, we demonstrate what
      happens to nursing work when management imposes rounding as a risk reduction
      strategy. In the case study outlined rounding was introduced across all wards in
      response to missed care, which in turn arose as a result of work intensification
      produced by efficiency, productivity, effectiveness and accountability demands.
      Rounding is a commercially sponsored practice consistent with new public
      management. Our study illustrates the impact that new public management
      strategies such as rounding have on how nurses work, both in terms of work
      intensity and in who controls their labour.

PMID- 26314695
TI  - Growth and Chemosensitivity of Gastric Adenocarcinoma and Non-Malignant Cell
      Lines in Response to Novel Anti-Cancer Drug Combinations.
AB  - BACKGROUND: To design novel polychemotherapy regimens for gastric adenocarcinoma
      therapy with wider therapeutic windows using a novel duplex drug (D-D). METHODS:
      Two gastric adenocarcinoma (MKN-45 and 23132/87) and 2 non-malignant (NHDF and
      CCL-241) cell lines were treated with different drug regimens that included
      different doses of the standard triple-drug combination epirubicin (E) +
      cisplatin (C) + 5-fluorouracil (5-FU, F), i.e. ECF, and a new D-D that combined
      2'-deoxy-5-fluorouridine (5FdU) and 3'ethinylcytidine. The cells were cultured
      for 14 days and the effect of the drug combinations was evaluated using CASY cell
      counting technology. RESULTS: Overall growth inhibition of the cell lines with
      ECF was not cancer cell line-specific. Replacing 5-FU in ECF with a D-D resulted
      in greater growth inhibition of cancer cells than of the non-malignant cell lines
      and the inversion of the chemosensitivity of MKN-45 and 23132/87 cells. The type
      and quantity of the combined drug regimen determined the cytotoxicity and
      chemosensitivity of the cell lines. CONCLUSION: The cytotoxicity and tumour-cell
      specificity of standard single drugs can be markedly changed and determined using
      multidrug combinations that include D-Ds.

PMID- 26314696
TI  - A Randomized Trial of Low-Flow Oxygen versus Nasal Continuous Positive Airway
      Pressure in Preterm Infants.
AB  - BACKGROUND: Nasal continuous positive airway pressure (nCPAP) stabilizes the
      residual volume and may decrease the risk of 'atelectotrauma', potentially
      promoting lung development in neonates. OBJECTIVES: To assess whether replacing
      nCPAP by low-flow O2 by nasal cannula affects lung function expressed as the
      arterial/alveolar oxygen tension ratio (a/A pO2 ratio) on postnatal day 28.
      METHODS: Preterm infants (birth weight <1,500 g and gestational age, GA >26 + 0
      weeks) stable on nCPAP between postnatal days 4 and 7 were randomized to nCPAP or
      low-flow O2 by nasal cannula (<0.2 liters/min). Study criteria defined how to
      wean/restart respiratory support or change from low-flow O2 to nCPAP and vice
      versa. Transcutaneous monitoring was used for the assessment of the a/A pO2 ratio
      on day 28 using a head box for all infants for accurate measurement and to
      eliminate possible effects from nCPAP or low-flow O2 on oxygen requirement.
      RESULTS: We enrolled 52 infants (nCPAP group n = 30 and low-flow O2 group n =
      22). The a/A pO2 ratio at 28 days was 0.43 +/- 0.17 (nCPAP group) versus 0.48 +/-
      0.18 (p = 0.36). The duration of nCPAP was 16.4 (low-flow group) versus 41.1 days
      (nCPAP group), p < 0.001. There was no difference between groups in the fraction
      needing any respiratory support at 36 weeks' corrected age, length of stay,
      weight at discharge, and relative weight gain. CONCLUSIONS: Replacing nCPAP by
      low-flow O2 in preterm infants with GA >26 weeks at the end of the first week of
      life did not seem to affect the a/A pO2 ratio or weight gain negatively. Thus,
      prolonged nCPAP seems not to have a positive effect on lung function at 28 days
      of life and replacement by low-flow O2 could reduce the cost of equipment and
      increase the ease of nursing.

PMID- 26314697
TI  - Prevalence of Renal Impairment in Patients With Rheumatoid Arthritis: Results
      From a Cross-Sectional Multicenter Study.
AB  - OBJECTIVE: To assess the prevalence and associations of renal dysfunction in
      patients with rheumatoid arthritis (RA). METHODS: COMEDRA is a French nationwide
      cross-sectional multicenter study on comorbidities in RA. Renal function was
      assessed from the estimated glomerular filtration rate (eGFR), using the
      Modification of Diet in Renal Disease equation. RA characteristics and risk
      factors for renal impairment were collected. Two logistic regression models, 1
      with and 1 without the Framingham Risk Score, were constructed from variables
      that were significantly associated with an eGFR of <60 ml/minute/1.73 m(2) or
      were clinically relevant. RESULTS: Of the 970 recruited patients, 931 were
      analyzed (women 79.6%, mean age 57.8 years, disease duration 11.1 years, Disease
      Activity Score in 28 joints using the erythrocyte sedimentation rate [DAS28-ESR]
      3.1). A total of 82 patients (8.8%) had an eGFR <60 ml/minute/1.73 m(2) and 9%
      had proteinuria. In univariate analysis, renal impairment was associated with age
      (P < 0.001), history of hypertension (P < 0.001), high systolic blood pressure (P
      = 0.03), and the Systematic Coronary Risk Evaluation (SCORE) equation (P =
      0.002), but not with sex, disease duration, disease activity (as assessed by
      DAS28-ESR), nonsteroidal antiinflammatory drug use, disease severity (erosions,
      joint replacement), or RA medications. Multivariate analysis models showed that
      age (odds ratio [OR] 1.05 [95% confidence interval (95% CI) 1.03-1.09]) and
      hypertension (OR 2.5 [95% CI 1.5-4.3]) were associated with renal impairment. A
      second model showed that the SCORE equation (OR 1.33 [95% CI 1.06-1.67]) was
      associated with renal impairment. CONCLUSION: Renal impairment is relatively
      common in RA and is associated with cardiovascular risk factors such as age,
      hypertension, and the SCORE equation but not with disease activity or severity.

PMID- 26314698
TI  - A structured multicomponent group programme for carers of people with acquired
      brain injury: Effects on perceived criticism, strain, and psychological distress.
AB  - OBJECTIVES: The purpose of this study was to examine whether a brief structured
      multicomponent group programme for carers of people with acquired brain injury
      (ABI) was effective in reducing carer distress, strain, and critical comments
      between carer and person with an ABI compared to a waiting list control
      condition. DESIGN: Waiting list controlled study. Pre- and post-test design with
      outcomes measured at induction, at the end of the intervention, and at the 3
      month follow-up. METHODS: One hundred and thirteen carers took part in the study:
      75 carers in the intervention group and 38 in the waiting list control group (2:1
      ratio). All participants completed assessments of caregiver strain (Caregiver
      Strain Index), perceived criticism towards and from the person with an ABI
      (Perceived Criticism Scale), and psychological distress (Hospital Anxiety and
      Depression Scale). The person with an ABI was also assessed on the Functional
      Independence Measure/Functional Assessment Measure. RESULTS: Using an intention
      to treat analysis, there were significant effects of group (intervention vs.
      waiting list control) at the 3-month follow-up on carers' perceptions of stress
      and strain resulting from caring, and perceptions of criticism received by the
      carer from the person with an ABI. A subsequent per-protocol analysis showed an
      additional reduction at 3 months in levels of criticism expressed towards the
      person with an ABI by the carer. There was no significant effect of the
      intervention on psychological distress. CONCLUSIONS: The structured
      multicomponent carers programme showed beneficial effects in terms of reducing
      carer strain and in the reduction of elements of perceived criticism at the 3
      month follow-up; however, it did not significantly affect psychological distress
      in carers, suggesting the need for additional support for this group of carers.
      STATEMENT OF CONTRIBUTION: What is already known on this subject? A number of
      studies have suggested that carers of people with acquired brain injury (ABI)
      experience greater levels of carer burden and mental health difficulties than
      carers of other patient groups. Previous interventional studies on ABI are few,
      and such studies have diverged in the extent to which they have been oriented
      towards education, psychological support, or management of behavioural
      difficulties, making results somewhat difficult to apply in community health
      settings with this potential client group. What does this study add? We develop,
      describe, and evaluate a brief structured multicomponent carers' training and
      support programme for carers of people with ABI. Not all outcomes were affected
      positively by the intervention. While the intervention successfully reduced carer
      strain and critical comments, distress did not significantly reduce compared to
      people in a waiting list control group. Carers who were spouses/partners and
      carers who were parents exhibited comparable levels of strain, distress, and
      perceived criticism. Younger carers reported significantly higher levels of
      distress and carer strain at induction to the programme. The positive effects of
      the programme were maintained for at least 3 months, suggesting that it may have
      initial validity for improving some of the negative aspects of the carer
      experience.

PMID- 26314699
TI  - Crocin and quercetin prevent PAT-induced apoptosis in mammalian cells:
      Involvement of ROS-mediated ER stress pathway.
AB  - Patulin (PAT) is a secondary metabolite produced by several species of the genera
      of Penicillium, Aspergillus, and Byssochlamys that can be found in rotting
      fruits, especially in apples and apple-based products. Exposure to this mycotoxin
      has been reported to induce intestinal and kidney injuries. The mechanism
      underlying such toxicity has been linked to the induction of apoptosis which
      occurred with reactive oxygen species production and endoplasmic reticulum (ER)
      stress induction. This study aimed to evaluate the effect of the two common
      dietary compounds Quercetin (QUER), a natural flavonoid, and Crocin (CRO), a
      natural carotenoid, on PAT-induced toxicity in human colon carcinoma (HCT116) and
      embryonic kidney cells (HEK293). We showed that antioxidant properties of QUER
      and CRO help to prevent ER stress activation and lipid peroxidation as evidenced
      by the reduction in GRP78 and GADD34 expressions and the decrease in
      malondialdehyde production. Furthermore, we demonstrated their ability to re
      establish the loss of the mitochondrial membrane potential to inhibit caspase 3
      activation and DNA fragmentation. (c) 2015 Wiley Periodicals, Inc. Environ
      Toxicol 31: 1851-1858, 2016.

PMID- 26314700
TI  - An Untargeted Metabolomics Analysis of Antipsychotic Use in Bipolar Disorder.
AB  - BACKGROUND: Second generation antipsychotic (SGA) use in bipolar disorder is
      common and has proven effective in short-term trials. There continues to be a
      lack of understanding of the mechanisms underlying many of their positive and
      negative effects in bipolar disorder. This study aimed to describe the metabolite
      profiles of bipolar subjects treated with SGAs by comparing to metabolite
      profiles of bipolar subjects treated with lithium, and schizophrenia subjects
      treated with SGAs. METHODS: Cross-sectional, fasting untargeted serum metabolomic
      profiling was conducted in 82 subjects diagnosed with bipolar I disorder (n = 30
      on SGAs and n = 32 on lithium) or schizophrenia (n = 20). Metabolomic profiles of
      bipolar subjects treated with SGAs were compared to bipolar subjects treated with
      lithium and schizophrenia subjects treated with SGAs using multivariate methods.
      RESULTS: Partial lease square discriminant analysis (PLS-DA) plots showed
      separation between bipolar subjects treated with SGAs, bipolar subjects treated
      with lithium, or schizophrenia subjects treated with SGAs. Top influential
      metabolite features were associated with several pathways including that of
      polyunsaturated fatty acids, pyruvate, glucose, and branched chain amino acids.
      CONCLUSIONS: The findings from this study require further validation in pre- and
      posttreated bipolar and schizophrenia subjects, but suggest that the
      pharmacometabolome may be diagnosis specific.

PMID- 26314701
TI  - Maintenance treatment with oral cyclophosphamide and bevacizumab in patients with
      recurrent epithelial ovarian cancer.
AB  - AIM: To evaluate the efficacy and safety of maintenance treatment with oral
      cyclophosphamide (Cy) and bevacizumab (Bev) in patients with recurrent ovarian
      cancer. PATIENTS & METHODS: Induction treatment consisted of cisplatin,
      epirubicin, Cy and Bev every 3 weeks, for a maximum of six cycles. Maintenance
      treatment consisted of oral Cy 50 mg, days 1-14 and Bev 15 mg/kg, every 3 weeks
      until disease progression occurred. RESULTS: In total, 39 patients were enrolled:
      after induction chemotherapy, the objective response was 74.3%. The median
      progression-free survival was 13.3 months, and the median overall survival was
      33.2 months. Toxicity during maintenance treatment was mild. CONCLUSION:
      Maintenance with Cy and Bev may achieve encouraging results in terms of
      progression-free survival and overall survival in recurrent ovarian cancer
      patients.

PMID- 26314702
TI  - Disruption of cortical integration during midazolam-induced light sedation.
AB  - This work examines the effect of midazolam-induced light sedation on intrinsic
      functional connectivity of human brain, using a randomized, double-blind, placebo
      controlled, cross-over, within-subject design. Fourteen healthy young subjects
      were enrolled and midazolam (0.03 mg/kg of the participant's body mass, to a
      maximum of 2.5 mg) or saline were administrated with an interval of one week.
      Resting-state fMRI was conducted before and after administration for each
      subject. We focus on two types of networks: sensory related lower-level
      functional networks and higher-order functions related ones. Independent
      component analysis (ICA) was used to identify these resting-state functional
      networks. We hypothesize that the sensory (visual, auditory, and sensorimotor)
      related networks will be intact under midazolam-induced light sedation while the
      higher-order (default mode, executive control, salience networks, etc.) networks
      will be functionally disconnected. It was found that the functional integrity of
      the lower-level networks was maintained, while that of the higher-level networks
      was significantly disrupted by light sedation. The within-network connectivity of
      the two types of networks was differently affected in terms of direction and
      extent. These findings provide direct evidence that higher-order cognitive
      functions including memory, attention, executive function, and language were
      impaired prior to lower-level sensory responses during sedation. Our result also
      lends support to the information integration model of consciousness.

PMID- 26314703
TI  - Differences of symptoms in head and neck cancer patients with and without
      lymphedema.
AB  - PURPOSE: Head and neck cancer (HNC) patients are at risk for developing external
      and internal lymphedema. Currently, no documentation of symptom differences
      between individuals with and without head and neck lymphedema is available. The
      purpose of this analysis was to examine symptom differences among HNC patients
      with and without lymphedema. METHODS: Data were drawn from three cross-sectional
      studies of HNC patients >3 months post-cancer treatment (total N = 163; 128
      patients with lymphedema, 35 without lymphedema). External lymphedema was
      evaluated via physical examination; internal lymphedema was identified through
      endoscopic examination. Participant's head and neck lymphedema status was
      categorized into two groups: no indication of external or internal lymphedema and
      at least some indication of external or internal lymphedema. Lymphedema Symptom
      Intensity and Distress Survey-Head and Neck (LSIDS-H&N) was used to assess
      symptom burden. Descriptive statistics, McNemar, chi-squared, Wilcoxon signed
      ranks, and Mann-Whitney tests were used. RESULTS: Twenty-three pairs of patients
      were identified and matched on the age, primary tumor site, tumor stage, and time
      since end of cancer treatment. Relative to patients without lymphedema, matched
      patients with lymphedema reported either increased symptom prevalence or severity
      or distress level for the following symptoms (prevalence differences of at least
      15 % between the matched groups and p < 0.05): (1) numbness; (2) tightness; (3)
      heaviness; (4) warmth; (5) pain without head/neck movement; (6) problems
      swallowing mashed or pureed foods; (7) trouble breathing; (8) blurred vision; (9)
      feel worse when flying in an airplane; and (10) swelling. CONCLUSIONS: Findings
      suggest that HNC-related lymphedema may be associated with substantial symptom
      burden. Studies with larger sample sizes are needed to replicate the findings.

PMID- 26314704
TI  - Illness perceptions among cancer survivors.
AB  - PURPOSE: The purpose of the study is to document in Hong Kong Chinese cancer
      survivors cross-sectional associations between illness perceptions, physical
      symptom distress and dispositional optimism. METHODS: A consecutive sample of
      1036 (response rate, 86.1%, mean age 55.18 years, 60% female) survivors of
      different cancers recruited within 6 months of completion of adjuvant therapy
      from Hong Kong public hospitals completed the Brief Illness Perception
      Questionnaire (B-IPQ), Chinese version of the Memorial Symptom Assessment Scale
      Short-Form (MSAS-SF), and the revised Chinese version of Life Orientation Test (C
      LOT-R), respectively. Stepwise multiple regression analyses examined adjusted
      associations. RESULTS: IPQ seriousness, symptom identity, illness concern, and
      emotional impact scores varied by cancer type (p < 0.01). Stress-related,
      lifestyle, environment, psychological/personality, and health-related factors
      were most frequently attributed causes of cancer. After adjustment for sample
      differences, physical symptom distress was significantly associated with all
      illness perception dimensions (p < 0.01), excepting control beliefs. Optimism was
      positively correlated with perceived personal and treatment control (p < 0.01)
      and illness understanding (p < 0.01), but negatively correlated with other IPQ
      dimensions (all p < 0.01). IPQ domain differences by cancer type were eliminated
      by adjustment for sample characteristics. CONCLUSION: Illness perceptions did not
      differ by cancer type. Greater physical symptom distress and lower levels of
      optimism were associated with more negative illness perceptions. IMPLICATIONS:
      Understanding how cancer survivors make sense of cancer can clarify an important
      aspect of adaptation. This in turn can inform interventions to facilitate
      adjustment. Knowledge contributions include evidence of physical symptom distress
      correlating with most dimensions of illness perception. Optimism was also
      associated with cancer survivors' illness perceptions.

PMID- 26314705
TI  - Cancer rehabilitation and palliative care: critical components in the delivery of
      high-quality oncology services.
AB  - Palliative care and rehabilitation practitioners are important collaborative
      referral sources for each other who can work together to improve the lives of
      cancer patients, survivors, and caregivers by improving both quality of care and
      quality of life. Cancer rehabilitation and palliative care involve the delivery
      of important but underutilized medical services to oncology patients by
      interdisciplinary teams. These subspecialties are similar in many respects,
      including their focus on improving cancer-related symptoms or cancer treatment
      related side effects, improving health-related quality of life, lessening
      caregiver burden, and valuing patient-centered care and shared decision-making.
      They also aim to improve healthcare efficiencies and minimize costs by means such
      as reducing hospital lengths of stay and unanticipated readmissions. Although
      their goals are often aligned, different specialized skills and approaches are
      used in the delivery of care. For example, while each specialty prioritizes goal
      concordant care through identification of patient and family preferences and
      values, palliative care teams typically focus extensively on using patient and
      family communication to determine their goals of care, while also tending to
      comfort issues such as symptom management and spiritual concerns. Rehabilitation
      clinicians may tend to focus more specifically on functional issues such as
      identifying and treating deficits in physical, psychological, or cognitive
      impairments and any resulting disability and negative impact on quality of life.
      Additionally, although palliative care and rehabilitation practitioners are
      trained to diagnose and treat medically complex patients, rehabilitation
      clinicians also treat many patients with a single impairment and a low symptom
      burden. In these cases, the goal is often cure of the underlying neurologic or
      musculoskeletal condition. This report defines and describes cancer
      rehabilitation and palliative care, delineates their respective roles in
      comprehensive oncology care, and highlights how these services can contribute
      complementary components of essential quality care. An understanding of how
      cancer rehabilitation and palliative care are aligned in goal setting, but
      distinct in approach may help facilitate earlier integration of both into the
      oncology care continuum-supporting efforts to improve physical, psychological,
      cognitive, functional, and quality of life outcomes in patients and survivors. 

PMID- 26314706
TI  - The level of association between functional performance status measures and
      patient-reported outcomes in cancer patients: a systematic review.
AB  - PURPOSE: The process of assessing patient symptoms and functionality using
      patient-reported outcomes (PROs) and functional performance status (FPS) is an
      essential aspect of patient-centered oncology research and care. However, PRO and
      FPS measures are often employed separately or inconsistently combined. Thus, the
      purpose of this study was to conduct a systematic review of the level of
      association between PRO and FPS measures to determine their differential or
      combined utility. METHODS: A systematic search was conducted using five databases
      (1966 to February 2014) to identify studies that described an association between
      PRO and FPS. Studies were excluded if they were non-cancer specific, did not
      include adults aged 18 or older, or were review articles. Publications were
      selected for review by consensus among two authors, with a third author
      arbitrating as needed. RESULTS: A total of 18 studies met inclusion criteria. FPS
      was primarily assessed by clinicians using the ECOG Performance Status or
      Karnofsky Performance Status measures. PROs were captured using a variety of
      measures, with numerous domains assessed (e.g., pain, fatigue, and general health
      status). Concordance between PROs and FPS measures was widely variable, falling
      in the low to moderate range (0.09-0.72). CONCLUSIONS: Despite consistency in the
      method of capture of PROs or FPS, domain capture varied considerably across
      reviewed studies. Irrespective of the method of capturing PROs or FPS, the
      quantified level of association between these two areas was moderate at best,
      providing evidence that FPS and PRO assessments offer unique information to
      assist clinicians in their decision-making.

PMID- 26314707
TI  - Methotrexate-Induced Cutaneous Erosions.

PMID- 26314708
TI  - Regulation of gene expression dynamics during developmental transitions by the
      Ikaros transcription factor.
AB  - The DNA-binding protein Ikaros is a potent tumor suppressor and hematopoietic
      regulator. However, the mechanisms by which Ikaros functions remain poorly
      understood, due in part to its atypical DNA-binding properties and partnership
      with the poorly understood Mi-2/NuRD complex. In this study, we analyzed five
      sequential stages of thymocyte development in a mouse strain containing a
      targeted deletion of Ikaros zinc finger 4, which exhibits a select subset of
      abnormalities observed in Ikaros-null mice. By examining thymopoiesis in vivo and
      in vitro, diverse abnormalities were observed at each developmental stage. RNA
      sequencing revealed that each stage is characterized by the misregulation of a
      limited number of genes, with a strong preference for stage-specific rather than
      lineage-specific genes. Strikingly, individual genes rarely exhibited Ikaros
      dependence at all stages. Instead, a consistent feature of the aberrantly
      expressed genes was a reduced magnitude of expression level change during
      developmental transitions. These results, combined with analyses of the interplay
      between Ikaros loss of function and Notch signaling, suggest that Ikaros may not
      be a conventional activator or repressor of defined sets of genes. Instead, a
      primary function may be to sharpen the dynamic range of gene expression changes
      during developmental transitions via atypical molecular mechanisms that remain
      undefined. 

PMID- 26314711
TI  - Stability of Fe-N-C Catalysts in Acidic Medium Studied by Operando Spectroscopy.
AB  - Fundamental understanding of non-precious metal catalysts for the oxygen
      reduction reaction (ORR) is the nub for the successful replacement of noble Pt in
      fuel cells and, therefore, of central importance for a technological
      breakthrough. Herein, the degradation mechanisms of a model high-performance Fe-N
      C catalyst have been studied with online inductively coupled plasma mass
      spectrometry (ICP-MS) and differential electrochemical mass spectroscopy (DEMS)
      coupled to a modified scanning flow cell (SFC) system. We demonstrate that Fe
      leaching from iron particles occurs at low potential (<0.7 V) without a direct
      adverse effect on the ORR activity, while carbon oxidation occurs at high
      potential (>0.9 V) with a destruction of active sites such as FeNx Cy species.
      Operando techniques combined with identical location-scanning transmission
      electron spectroscopy (IL-STEM) identify that the latter mechanism leads to a
      major ORR activity decay, depending on the upper potential limit and electrolyte
      temperature. Stable operando potential windows and operational strategies are
      suggested for avoiding degradation of Fe-N-C catalysts in acidic medium. 

PMID- 26314709
TI  - Increased mitochondrial function downstream from KDM5A histone demethylase
      rescues differentiation in pRB-deficient cells.
AB  - The retinoblastoma tumor suppressor protein pRb restricts cell growth through
      inhibition of cell cycle progression. Increasing evidence suggests that pRb also
      promotes differentiation, but the mechanisms are poorly understood, and the key
      question remains as to how differentiation in tumor cells can be enhanced in
      order to diminish their aggressive potential. Previously, we identified the
      histone demethylase KDM5A (lysine [K]-specific demethylase 5A), which
      demethylates histone H3 on Lys4 (H3K4), as a pRB-interacting protein
      counteracting pRB's role in promoting differentiation. Here we show that loss of
      Kdm5a restores differentiation through increasing mitochondrial respiration. This
      metabolic effect is both necessary and sufficient to induce the expression of a
      network of cell type-specific signaling and structural genes. Importantly, the
      regulatory functions of pRB in the cell cycle and differentiation are distinct
      because although restoring differentiation requires intact mitochondrial
      function, it does not necessitate cell cycle exit. Cells lacking Rb1 exhibit
      defective mitochondria and decreased oxygen consumption. Kdm5a is a direct
      repressor of metabolic regulatory genes, thus explaining the compensatory role of
      Kdm5a deletion in restoring mitochondrial function and differentiation.
      Significantly, activation of mitochondrial function by the mitochondrial
      biogenesis regulator Pgc-1alpha (peroxisome proliferator-activated receptor gamma
      coactivator 1alpha; also called PPARGC1A) a coactivator of the Kdm5a target
      genes, is sufficient to override the differentiation block. Overexpression of Pgc
      1alpha, like KDM5A deletion, inhibits cell growth in RB-negative human cancer
      cell lines. The rescue of differentiation by loss of KDM5A or by activation of
      mitochondrial biogenesis reveals the switch to oxidative phosphorylation as an
      essential step in restoring differentiation and a less aggressive cancer
      phenotype. 

PMID- 26314712
TI  - Cardiovascular disease prevention: Mind the gap...

PMID- 26314710
TI  - Proteomic analysis of pRb loss highlights a signature of decreased mitochondrial
      oxidative phosphorylation.
AB  - The retinoblastoma tumor suppressor (pRb) protein associates with chromatin and
      regulates gene expression. Numerous studies have identified Rb-dependent RNA
      signatures, but the proteomic effects of Rb loss are largely unexplored. We
      acutely ablated Rb in adult mice and conducted a quantitative analysis of RNA and
      proteomic changes in the colon and lungs, where Rb(KO) was sufficient or
      insufficient to induce ectopic proliferation, respectively. As expected, Rb(KO)
      caused similar increases in classic pRb/E2F-regulated transcripts in both
      tissues, but, unexpectedly, their protein products increased only in the colon,
      consistent with its increased proliferative index. Thus, these protein changes
      induced by Rb loss are coupled with proliferation but uncoupled from
      transcription. The proteomic changes in common between Rb(KO) tissues showed a
      striking decrease in proteins with mitochondrial functions. Accordingly, RB1
      inactivation in human cells decreased both mitochondrial mass and oxidative
      phosphorylation (OXPHOS) function. RB(KO) cells showed decreased mitochondrial
      respiratory capacity and the accumulation of hypopolarized mitochondria.
      Additionally, RB/Rb loss altered mitochondrial pyruvate oxidation from (13)C
      glucose through the TCA cycle in mouse tissues and cultured cells. Consequently,
      RB(KO) cells have an enhanced sensitivity to mitochondrial stress conditions. In
      summary, proteomic analyses provide a new perspective on Rb/RB1 mutation,
      highlighting the importance of pRb for mitochondrial function and suggesting
      vulnerabilities for treatment. 

PMID- 26314713
TI  - Diabetes in patients with HIV: patient characteristics, management and screening.
AB  - BACKGROUND: As HIV management has become more successful during the past years,
      non-communicable diseases have become more prevalent among HIV-infected
      individuals. As a result, more HIV-infected patients die of cardiovascular
      diseases, with diabetes being one of the main risk factors. This study evaluates
      screening and management of diabetes among HIV-infected patients in a university
      hospital in the Netherlands. METHODS: We examined clinical characteristics,
      glycaemic control and cardiovascular risk management of HIV-infected patients
      with coexisting diabetes, and determined the frequency of diabetes screening in
      those without. RESULTS: Of 518 HIV-infected patients, 28 had been diagnosed with
      diabetes (5.4%), mostly (20/28) after being diagnosed with HIV. Patients with
      coexisting diabetes were older, had a longer duration of HIV, lower CD4 cell
      counts and higher body mass index (BMI), and were more likely to use aspirin,
      statins and antihypertensive medication than those without diabetes (all p <
      0.05). HbA1c values were below 7% (53 mmol/mol) in 54% of patients. Targets for
      systolic blood pressure (< 140 mmHg), LDL cholesterol (< 2.5 mmol/l) and BMI (<
      25 kg/m2) were achieved by 82%, 50% and 29% of patients, respectively. Annual
      ophthalmology examination, screening for microalbuminuria and foot control were
      rarely performed. Among the patients without known diabetes, diabetes screening
      during the past year had been performed using (non-fasting) plasma glucose in 56%
      and HbA1c in 10%, but 42% of patients had not been screened. CONCLUSION: For HIV
      infected individuals with diabetes, glycaemic control and cardiovascular risk
      management were reasonable, but screening for microvascular complications was
      rarely performed. Annual diabetes screening of HIV-infected patients was not
      routine.

PMID- 26314714
TI  - Adherence to guidelines to prevent cardiovascular diseases: The LifeLines cohort
      study.
AB  - BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death worldwide.
      While there is indisputable evidence that statin treatment reduces the burden of
      CVD, undertreatment remains a concern for primary and secondary prevention. The
      aim of this study was to assess the use of lipid-lowering drugs (LLD) among
      70,292 individuals in the Netherlands as a proxy of adherence to the national
      guideline for prevention and treatment of CVD. METHODS: LifeLines is a population
      based prospective cohort study in the three Northern provinces of the
      Netherlands. At baseline, all participants completed questionnaires, and
      underwent a physical examination and lab testing. The national guidelines were
      used to assess how many participants were eligible for LLD prescription and we
      analysed how many indeed reported LLD use. RESULTS: For primary prevention, 77%
      (2515 of 3268) of those eligible for LLD treatment did not report using these
      drugs, while for secondary prevention this was 31% (403 of 1302). Patients with
      diabetes mellitus were treated best (67%) for primary prevention. Notably, of the
      patients with stroke, only 47% (182 of 386) reported LLD treatment. CONCLUSION:
      Despite clear guidelines and multiple national initiatives to improve CVD risk
      management, adherence to guidelines for the treatment of CVD in the Netherlands
      remains a major challenge. This study calls out for improving public awareness of
      CVD and to improve primary and secondary prevention to prevent unnecessary CVD
      related morbidity and mortality.

PMID- 26314715
TI  - Favourable SVR12 rates with boceprevir or telaprevir triple therapy in HIV/HCV
      coinfected patients.
AB  - BACKGROUND: Recent publications have reported superior efficacy of telaprevir- or
      boceprevir-based triple therapy over conventional peginterferon-alfa/ribavirin
      therapy, albeit with varying rates of adverse events and treatment
      discontinuations in HIV/HCV coinfected patients. Therefore, the aim of this study
      is to describe the effectiveness of triple therapy in an HIV/HCV coinfection
      cohort in the Netherlands. METHODS: HIV-infected patients with chronic HCV
      genotype 1 starting triple therapy including either boceprevir or telaprevir were
      enrolled, 26% had F3-F4 fibrosis. Data were assessed at Week 4, 8, 12, 24, 48 and
      SVR12 (i.e. absence of detectable plasma HCV RNA 12 weeks after completion of
      treatment). Failure was defined as discontinuation of treatment due to
      virological failure, adverse events or loss to follow-up. RESULTS: A total of 53
      HIV/HCV coinfected patients started peginterferon-alfa/ribavirin therapy with
      either boceprevir (n = 29) or telaprevir (n = 24). SVR12 was achieved in 19 (66%)
      of the boceprevir-treated and 15 (63%) of the telaprevir-treated patients. Both
      prior relapse and achievement of a rapid virological response were associated
      with a higher SVR12 rate. Non- response, breakthrough and relapse occurred in 4,
      1 and 5 patients on boceprevir and 3, 2, 2 on telaprevir, respectively. One
      patient was lost to follow-up and one patient died due to progression of liver
      failure. Except for these two patients, no treatment discontinuations were
      observed due to adverse events. CONCLUSION: In HIV/HCV coinfected patients,
      boceprevir or telaprevir triple therapy was well tolerated and resulted in
      favourable SVR12 rates comparable with previous publications concerning HCV mono
      infected patients.

PMID- 26314716
TI  - What are we waiting for? Factors influencing completion times in an academic and
      peripheral emergency department.
AB  - BACKGROUND: A long completion time in the Emergency Department (ED) is associated
      with higher morbidity and in-hospital mortality. A completion time of more than
      four hours is a frequently used cut-off point. Mostly, older and sicker patients
      exceed a completion time of four hours on the ED. The primary aim was to examine
      which factors currently contribute to overcrowding and a time to completion of
      more than four hours on the EDs of two different hospitals, namely: the VU
      Medical Center (VUmc), an academic level 1 trauma centre and the St. Antonius
      Hospital, a large community hospital in Nieuwegein. In addition, we compared the
      differences between these hospitals. METHODS: In this observational study, the
      time steps in the process of diagnosing and treatment of all patients visiting
      the EDs of the two hospitals were measured for four weeks. Patients triaged as
      Emergency Severity Index (ESI) category 2/3 or Manchester Triage System (MTS)
      orange/yellow were followed more closely and prospectively by researchers for
      detailed information in the same period from 12.00-23.00 hrs. RESULTS: In the
      VUmc, 89% of the patients had a completion time of less than four hours. The
      average completion time (n = 2262) was 2:10 hours, (median 1:51 hours, range:
      0:05-12:08). In the St. Antonius Hospital, 77% of patients had a completion time
      shorter than four hours (n = 1656). The average completion time in hours was 2:49
      (n = 1655, median 2:34, range: 0:08-11:04). In the VUmc, a larger percentage of
      ESI 1, 2 and 3 patients did not achieve the 4-hour target (14%, 20% and 19%)
      compared with ESI 4 and 5 patients (2.7% and 0%), p < 0.001. At the St. Antonius
      Hospital, a greater percentage of orange and yellow categorised patients exceeded
      four hours on the ED (32% and 28%) compared with red (8%) and green/blue (13%), p
      < 0.001. For both hospitals there was a significant dependency between exceeding
      four hours on the ED and the following: whether a consultation was performed (p <
      0.001), the number of radiology tests performed (p < 0.001), and an age above 65
      years. CONCLUSION: Factors leading to ED stagnation were similar in both
      hospitals, namely old age, treatment by more than one speciality and undergoing
      radiological tests. Uniform remedial measures should be taken on a nationwide
      level to deal with these factors to reduce stagnation in the EDs.

PMID- 26314717
TI  - Thinking beyond the mass: ANCA-associated vasculitis mimicking a pancreatic
      malignancy.
AB  - Isolated pancreatic involvement is a rare initial presentation in patients with
      ANCA-associated vasculitis. We report a patient with a suspected malignant
      pancreatic mass, referred to our hospital for pancreaticoduodenectomy. However,
      the pancreatic mass proved to be the initial manifestation of ANCA-associated
      vasculitis. 

PMID- 26314718
TI  - Clozapine intoxication due to cessation of smoking and infection.
AB  - We report on a patient on clozapine treatment who was admitted to our hospital
      with pneumonia. He had stopped smoking a few weeks before admission. The serum
      clozapine rose to a toxic level, most likely due to the combination of infection
      and smoking cessation. Physicians and pharmacists are often not aware of risk
      factors for decreased metabolism of clozapine. 

PMID- 26314719
TI  - A potentially hazardous object with benign appearance at the outset.

PMID- 26314721
TI  - A 68-year-old man with bilateral axillary swelling.

PMID- 26314723
TI  - An 86-year-old patient with a slowly progressive painless swelling on his scalp.

PMID- 26314725
TI  - Infliximab for treatment of pyoderma gangrenosum.

PMID- 26314726
TI  - Increasing the Expected Value to Society of Clinical Research Studies?

PMID- 26314727
TI  - Implementation of Patient Decision Support Interventions in Primary Care: The
      Role of Relational Coordination.
AB  - BACKGROUND: The benefits of patient decision support interventions (DESIs) have
      been well documented. However, DESIs remain difficult to incorporate into
      clinical practice. Relational coordination (RC) has been shown to improve
      performance and quality of care in health care settings. This study aims to
      demonstrate how applying RC theory to DESI implementation could elucidate
      underlying issues limiting widespread uptake. METHODS: Five primary care clinics
      in Northern California participated in a DESI implementation project. We used a
      deductive thematic approach guided by behaviors outlined in RC theory to analyze
      qualitative data collected from ethnographic field notes documenting the
      implementation process and focus groups with health care professionals. We then
      systematically compared the qualitative findings with quantitative DESI
      distribution data. RESULTS: Based on DESI distribution rates, clinics were placed
      into 3 performance categories: high, middle, and low. Qualitative data
      illustrated how each clinic's performance related to RC behaviors. Consistent
      with RC theory, the high-performing clinic exhibited frequent, timely, and
      accurate communication and positive working relationships. The 3 middle
      performing clinics exhibited high-quality communication within physician-staff
      teams but limited communication regarding DESI implementation across the clinic.
      The lowest-performing clinic was characterized by contentious relationships and
      inadequate communication. LIMITATIONS: Limitations of the study include nonrandom
      selection of clinics and limited geographic diversity. In addition, ethnographic
      data collected documented only DESI implementation practices and not larger staff
      interactions contributing to RC. CONCLUSIONS: These findings suggest that a high
      level of RC within clinical settings may be a key component and facilitator of
      successful DESI implementation. Future attempts to integrate DESIs into clinical
      practice should consider incorporating interventions designed to increase
      positive RC behaviors as a potential means to improve uptake.

PMID- 26314728
TI  - Health Condition Impacts in a Nationally Representative Cross-Sectional Survey
      Vary Substantially by Preference-Based Health Index.
AB  - IMPORTANCE: Many cost-utility analyses rely on generic utility measures for
      estimates of disease impact. Commonly used generic preference-based indexes may
      generate different absolute estimates of disease burden despite sharing anchors
      of dead at 0 and full health at 1.0. OBJECTIVE: We compare the impact of 16
      prevalent chronic health conditions using 6 utility-based indexes of health and a
      visual analog scale. DESIGN: Data were from the National Health Measurement Study
      (NHMS), a cross-sectional telephone survey of 3844 adults aged 35 to 89 years in
      the United States. MAIN OUTCOME MEASURES: The NHMS included the EuroQol-5D-3L,
      Health and Activities Limitation Index (HALex), Health Utilities Index Mark 2
      (HUI2) and Mark 3 (HUI3), preference-based scoring for the SF-36v2 (SF-6D),
      Quality of Well-Being Scale, and visual analog scale. Respondents self-reported
      16 chronic conditions. Survey-weighted regression analyses for each index with
      all health conditions, age, and sex were used to estimate health condition impact
      estimates in terms of quality-adjusted life years (QALYs) lost over 10 years. All
      analyses were stratified by ages 35 to 69 and 70 to 89 years. RESULTS: There were
      significant differences between the indexes for estimates of the absolute impact
      of most conditions. On average, condition impacts were the smallest with the SF
      6D and EQ-5D-3L and the largest with the HALex and HUI3. Likewise, the estimated
      loss of QALYs varied across indexes. Condition impact estimates for EQ-5D-3L,
      HUI2, HUI3, and SF-6D generally had strong Spearman correlations across
      conditions (i.e., >0.69). LIMITATIONS: This analysis uses cross-sectional data
      and lacks health condition severity information. CONCLUSIONS: Health condition
      impact estimates vary substantially across the indexes. These results imply that
      it is difficult to standardize results across cost-utility analyses that use
      different utility measures.

PMID- 26314729
TI  - Body mass index mediates inflammatory response to acute dietary challenges.
AB  - SCOPE: Acute metabolic challenges provide an opportunity to identify mechanisms
      of metabolic and nutritional health. In this study, we assessed the
      transcriptomic response to oral glucose and lipid challenges in a cohort of
      individuals ranging in age and BMI. The main goal is to identify whether BMI can
      mediate the metabolic and transcriptional response to dietary challenges, and the
      differences between lipid and glucose tests. METHODS AND RESULTS: Two hundred
      fourteen healthy adults were assigned to the challenges and twenty-three
      individuals were selected for further transcriptomic proofing, using microarray
      analysis of peripheral blood mononuclear cells. Through linear-mixed models and
      network analysis, different sets of transcripts and pathways were identified that
      responded to the challenges depending on BMI. Different transcripts that
      responded to the lipid and glucose tests, independently of BMI, were also
      identified. In the network analysis, inflammatory and adhesion processes were
      strongly represented for both challenges. CONCLUSION: Our results indicate that
      BMI is strongly linked to the transcriptomic and metabolic response to acute
      challenges. The emerging biological processes are mainly inflammation-related
      pathways, highlighting an interconnection between obesity, inflammation/adhesion,
      and response to nutritional challenge. The comparison between lipid and glucose
      challenges shows how these trigger a substantially different molecular response.

PMID- 26314730
TI  - In response.

PMID- 26314731
TI  - Stigma related to labels and symptoms in individuals at clinical high-risk for
      psychosis.
AB  - BACKGROUND: Despite advances that the psychosis "clinical high-risk" (CHR)
      identification offers, risk of stigma exists. Awareness of and agreement with
      stereotypes has not yet been evaluated in CHR individuals. Furthermore, the
      relative stigma associated with symptoms, as opposed to the label of risk, is not
      known, which is critical because CHR identification may reduce symptom-related
      stigma. METHODS: Thirty-eight CHR subjects were ascertained using standard
      measures from the Center of Prevention and Evaluation/New York State Psychiatric
      Institute/ Columbia University. Labeling-related measures adapted to the CHR
      group included "stereotype awareness and self-stigma" ("Stereotype awareness",
      "Stereotype Agreement", "Negative emotions [shame]"), and a parallel measure of
      "Negative emotions (shame)" for symptoms. These measures were examined in
      relation to symptoms of anxiety and depression, adjusting for core CHR symptoms
      (e.g. attenuated psychotic symptoms). RESULTS: CHR participants endorsed
      awareness of mental illness stereotypes, but largely did not themselves agree
      with these stereotypes. Furthermore, CHR participants described more stigma
      associated with symptoms than they did with the risk-label itself. Shame related
      to symptoms was associated with depression, while shame related to the risk-label
      was associated with anxiety. CONCLUSION: Both stigma of the risk-label and of
      symptoms contribute to the experience of CHR individuals. Stereotype awareness
      was relatively high and labeling-related shame was associated with increased
      anxiety. Yet limited agreement with stereotypes indicated that labeling-related
      stigma had not fully permeated self-conceptions. Furthermore, symptom-related
      stigma appeared more salient overall and was linked with increased depression,
      suggesting that alleviating symptom-related shame via treating symptoms might
      provide major benefit.

PMID- 26314732
TI  - Orange-Fleshed Sweet Potato: Successes and Remaining Challenges of the
      Introduction of a Nutritionally Superior Staple Crop in Mozambique.
AB  - BACKGROUND: Chronic vitamin A deficiency affects both women and children in
      Mozambique and populations worldwide and cannot be addressed through
      supplementation alone. Food-based approaches encouraging the consumption of
      vitamin A-rich foods, such as the orange-fleshed sweet potato (OFSP), have the
      potential to positively affect vitamin A status. A range of OFSP varieties have
      been introduced in sub-Saharan Africa in rural and urban environments and
      emergency and nonemergency contexts. OBJECTIVE: To highlight the successes to
      date and remaining challenges of the introduction of OFSP to increase vitamin A
      consumption in Mozambique, collating a time line of key events. METHODS: A
      systematic review of literature using The Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses. RESULTS: The systematic search resulted in
      20 studies that met inclusion criteria. Data extracted include author and year,
      study location and duration, project partners, project title, sample size and
      characteristics, objectives, methods and measures, and outcomes. CONCLUSIONS:
      Orange-fleshed sweet potatoes are widely accepted by Mozambican farmers and
      consumers, and various studies show a positive impact on vitamin A status due to
      the introduction of this nutritionally superior staple crop. Remaining challenges
      include vine preservation, pest and disease management, market development, and
      storage and processing.

PMID- 26314733
TI  - Inflammation and Vitamin A.
AB  - BACKGROUND: Serum retinol concentrations are homeostatically controlled and only
      fall when liver stores of vitamin A are very low. Nevertheless, low
      concentrations of serum retinol occur in apparently healthy people where there is
      no evidence of vitamin A deficiency (VAD). OBJECTIVE: To determine the reason for
      low serum vitamin A concentrations where there is no VAD. METHODS: We observed
      that elevated acute-phase protein (APP) concentrations often accompanied low
      retinol concentrations, and we developed a model of the inflammatory response to
      categorize 4 groups of participants termed reference (no raised APP), incubation
      (raised acute APP only), early convalescence (both acute and chronic APP raised),
      and late convalescence (raised chronic APP only). We identified 7 studies with
      participants who could be allocated to the 4 groups, and using meta-analysis
      methods we calculated correction (ie, multiplication) factors 1.13, 1.24, and
      1.11 to remove the influence of inflammation from the incubation, early, and late
      convalescent groups, respectively. CONCLUSION: In nutrition surveys or
      intervention studies to measure vitamin A status, workers should measure APP and
      correct retinol concentrations using the multiplication factors where
      inflammation is found.

PMID- 26314734
TI  - The Impact of Marketing of Breast-Milk Substitutes on WHO-Recommended
      Breastfeeding Practices.
AB  - BACKGROUND: Suboptimal breastfeeding results in 800 000 child deaths annually.
      There are multiple causes of suboptimal breastfeeding, including marketing of
      breast-milk substitutes. OBJECTIVES: To describe sales and marketing of breast
      milk substitutes and their influence on World Health Organization-recommended
      breastfeeding behaviors, focusing on low- and middle-income countries. METHODS:
      Literature review. RESULTS: Global sales of breast-milk substitutes reached US$40
      billion in 2013. Growth in sales exceeds 10% annually in many low- and middle
      income countries, while it is close to stagnant in high-income countries. Breast
      milk substitutes are marketed directly to consumers via mass media and print
      advertisements and indirectly via incentives, free supplies, and promotions to
      and through health workers and facilities, retailers, and policy makers. Internet
      marketing via company web sites and social media is on the rise. Marketing
      influences social norms by making formula use seem to be extensive, modern, and
      comparable to or better than breast milk. Clear evidence of a negative impact is
      found when breast-milk substitutes are provided for free in maternity facilities
      and when they are promoted by health workers and in the media. Influences through
      other channels are plausible, but rigorous studies are lacking. It was not
      possible with the data available to quantify the impact of marketing relative to
      other factors on suboptimal breastfeeding behaviors. Marketing remains widespread
      even in countries that have adopted the International Code of Marketing of Breast
      milk Substitutes to restrict such activities. CONCLUSION: Adoption of stricter
      regulatory frameworks coupled with independent, quantitative monitoring and
      compliance enforcement are needed to counter the impacts of formula marketing
      globally.

PMID- 26314735
TI  - Remembering Jeanette Snyder Brown (1925-2014).
AB  - Jeanette Snyder Brown (universally called Jan) was associated with the Department
      of Plant Biology, Carnegie Institution for Science (until recently Carnegie
      Institution of Washington) over a period of 37 years. Jan has left a scientific
      legacy of extensive publications concerned with photosynthetic pigments and their
      organization, and a historic collection of portraits of scientists who were
      prominent during her long tenure in the Department of Plant Biology. This legacy
      will stand for many years to come. 

PMID- 26314736
TI  - GlycoMob: an ion mobility-mass spectrometry collision cross section database for
      glycomics.
AB  - Ion mobility mass spectrometry (IM-MS) is a promising analytical technique for
      glycomics that separates glycan ions based on their collision cross section (CCS)
      and provides glycan precursor and fragment masses. It has been shown that
      isomeric oligosaccharide species can be separated by IM and identified on basis
      of their CCS and fragmentation. These results indicate that adding CCSs
      information for glycans and glycan fragments to searchable databases and analysis
      pipelines will increase identification confidence and accuracy. We have developed
      a freely accessible database, GlycoMob ( http://www.glycomob.org ), containing
      over 900 CCSs values of glycans, oligosaccharide standards and their fragments
      that will be continually updated. We have measured the absolute CCSs of
      calibration standards, biologically derived and synthetic N-glycans ionized with
      various adducts in positive and negative mode or as protonated (positive ion) and
      deprotonated (negative ion) ions.

PMID- 26314737
TI  - Emotional correlates of unirhinal odour identification.
AB  - It seems self-evident that smell profoundly shapes emotion, but less clear is the
      nature of this interaction. Here, we sought to determine whether the ability to
      identify odours co-varies with self-reported feelings of empathy and emotional
      expression recognition, as predicted if the two capacities draw on common
      resource. Thirty-six neurotypical volunteers were administered the Alberta Smell
      Test, the Interpersonal Reactivity Index and an emotional expression recognition
      task. Statistical analyses indicated that feelings of emotional empathy
      positively correlated with odour discrimination in right nostril, while the
      recognition of happy and fearful facial expressions positively correlated with
      odour discrimination in left nostril. These results uncover new links between
      olfactory discrimination and emotion which, given the ipsilateral configuration
      of the olfactory projections, point towards intra- rather than inter-hemispheric
      interaction. The results also provide novel support for the proposed
      lateralization of emotional empathy and the recognition of facial expression, and
      give reason to further explore the diagnostic sensitivity of smell tests because
      reduced sensitivity to others' emotions can mark the onset of certain
      neurological diseases. 

PMID- 26314738
TI  - The assumed relation between occupation and inequality in health.
AB  - BACKGROUND: Occupational science and therapy scholars have argued that research
      on inequality in health is needed. Simultaneously, a knowledge gap between how to
      understand and take action on health inequalities exists in occupational science
      and therapy. OBJECTIVE: To identify how inequality in health, high-risk areas of
      health, and engagement in health for low-income adult citizens have been
      described and conceptualized in contemporary occupational science and therapy
      literature. MATERIAL AND METHODS: A structured literature review of 37
      publications in occupational science and therapy literature, published from 2004
      to 2014. FINDINGS: The review revealed several descriptions and
      conceptualizations based on environmental, social, cultural, historical, and
      personal perspectives on occupation and already existing occupational science
      concepts. However, these descriptions were mainly based on assumptions regarding
      the relation between occupation and inequality in health, and statements on the
      need to explore this relation. CONCLUSION: Basic theory and reasoning, as well as
      empirical studies, on inequality in health are missing in occupational science
      and therapy. Based on the findings and theoretical trends, the authors suggest a
      transactional perspective on occupation is a possible frame for understanding
      inequality in health and related issues.

PMID- 26314739
TI  - Systemic Therapy for HER2-Positive Central Nervous System Disease: Where We Are
      and Where Do We Go From Here?
AB  - Patients with human epidermal growth factor receptor 2 (HER2)-positive breast
      cancer are at an increased risk of developing brain metastases. The incidence and
      prevalence of central nervous system (CNS) disease are increasing due to improved
      survival, which can be attributed to better systemic therapies for extracranial
      disease. The current standard of care for brain metastases includes a combination
      of surgery and/or radiation. Systemic therapies are typically reserved for
      patients with intracranial progression following radiation, due to their limited
      ability to cross the blood-brain barrier. None of the available anti-HER2 agents
      (trastuzumab, lapatinib, pertuzumab, and ado-trastuzumab emtansine (T-DM1)) are
      currently approved for the treatment of brain metastases. Research is underway
      evaluating novel anti-HER2 agents, which have demonstrated CNS activity. This
      article discusses the current data on using anti-HER2 therapies to treat CNS
      disease as well as the newer anti-HER2 agents, which may overcome the current
      challenges faced in treating brain metastases in the HER2-positive patient
      population. 

PMID- 26314741
TI  - [Characteristics of anesthesia in patients with MELAS syndrome: Case report of
      anesthesia in video-assisted thoracoscopy].
AB  - The mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like
      episodes (MELAS) syndrome is a disease triggered by a disorder in energy
      production within mitochondria. The cause of this syndrome is a mutation in the
      mitochondrial DNA where in 80% of cases an A-to-G mutation is present at
      nucleotide 3243 and with a prevalence of 18.4/100,000 in the population.
      Predominantly affected are organ systems with a high energy metabolism, such as
      the heart, brain and musculature. During the premedication visit a thorough
      patient history and examination with respect to neurological impairments must be
      carried out. Epilepsy and the appropriate permanent medication lead to possible
      alterations in effectiveness of anesthetics and muscle relaxants which are
      difficult to predict. An extensive patient cardiac history and a preoperative
      electrocardiogram (ECG) for an appraisal of possible disorders in the cardiac
      conduction system and when necessary extended cardiac diagnostics, are
      recommended. The monitoring must be adapted depending on the functional
      limitations and the forthcoming intervention and when necessary a postoperative
      surveillance in an intensive care unit should be initiated. Knowledge of the
      special features of MELAS syndrome in association with a consideration of the
      characteristics of anesthesia in MELAS patients and an individually adapted
      intensified perioperative surveillance, can contribute to a reduction in
      perioperative morbidity in patients suffering from MELAS syndrome.

PMID- 26314740
TI  - The PRECious trial PREdiction of Complications, a step-up approach, CRP first
      followed by CT-scan imaging to ensure quality control after major abdominal
      surgery: study protocol for a stepped-wedge trial.
AB  - BACKGROUND: After major abdominal surgery (MAS), 20% of patients endure major
      complications, which require invasive treatment and are associated with increased
      morbidity and mortality. A quality control algorithm after major abdominal
      surgery aimed at early identification of patients at risk of developing major
      complications can decrease associated morbidity and mortality. Literature studies
      show promising results for C-reactive protein (CRP) as an early marker for
      postoperative complications, however clinical significance has yet to be
      determined. METHODS: A multicenter, stepped wedge, prospective clinical trial
      including all adult patients planned to undergo elective MAS. The first period
      consists of standard postoperative monitoring, which entails on demand additional
      examinations. This is followed by a period with implementation of postoperative
      control according to the PRECious protocol, which implicates standardized
      measurement of CRP levels. If CRP levels exceed 140 mg/L on postoperative day 3,4
      or 5, an enhanced CT-scan is performed. Primary outcome in this study is a
      combined primary outcome, entailing all morbidity and mortality due to
      postoperative complications. Complications are graded according to the Clavien
      Dindo classification. Secondary outcomes are hospital length of stay, patients
      reported outcome measures (PROMs) and cost-effectiveness. Data will be collected
      during admission, three months and one year postoperatively. Approval by the
      medical ethics committee of the VU University Medical Center was obtained (ID
      2015.114). DISCUSSION: the PRECious trial is a stepped-wedge, multicenter, open
      label, prospective clinical trial to determine the effect of a standardized
      postoperative quality control algorithm on postoperative morbidity and mortality,
      and cost-effectiveness. TRIAL REGISTRATION: www.ClinicalTrials.gov, NCT02102217.
      Registered 5 February 2015.

PMID- 26314742
TI  - [Partial anomalous pulmonary venous connection as incidental finding: Explanation
      for apparently paradoxical central venous blood gas analysis results].
AB  - A partial anomalous pulmonary venous connection (PAPVC) is a congenital
      abnormality of the great thoracic vessels the incidence of which is
      underestimated and is associated with a left-right shunt. It rarely develops into
      a right-sided cardiac insufficiency. Because of the mostly low left-right shunt
      volume, a PAPVC is often asymptomatic and mostly incidentally detected in
      advanced age. Incorrect positioning of a central venous catheter or paradoxical
      blood gas parameters can serve to indicate the presence of a PAPVC. This article
      presents the case a 50-year-old patient with a PAPVC of the left upper lobe
      pulmonary vein draining into the left innominate vein without prior clinical
      symptoms. Blood gas analyses from the superior vena cava, where the catheter
      placement was confirmed by computed tomography angiography, showed unexplainable
      arterial values. The anatomical abnormality was confirmed by computed tomography.

PMID- 26314743
TI  - [Certification for Surgical Manager. A Prequalification of the Association for
      Surgical Management e.V. (VOPM)].

PMID- 26314744
TI  - Vitreous cysts in patients with retinitis pigmentosa.
AB  - PURPOSE: To determine the prevalence of vitreous cysts in patients with retinitis
      pigmentosa (RP). METHODS: We retrospectively reviewed the charts of 435
      consecutive patients diagnosed as having typical RP. RESULTS: Vitreous cysts were
      diagnosed in 37 eyes of 28 patients with RP (13 males and 15 females; mean age
      47.0 +/- 19.8 years; range 15-79 years), for an overall prevalence of 6.4%. The
      cysts were observed bilaterally in nine of the patients (32.1%). Among these 28
      patients, 11 (39.3%) were younger than 40 years. In all, 81.8% of the vitreous
      cysts were detected around the optic nerve head. CONCLUSIONS: We demonstrated
      that the prevalence of vitreous cysts was 6.4% in patients with RP. These cysts
      were considered to be asymptomatic.

PMID- 26314745
TI  - Correlation between central retinal thickness after successful macular hole
      surgery and visual outcome.
AB  - PURPOSE: To evaluate the correlation between central retinal thickness (CRT)
      after vitreous surgery and final visual outcome in eyes with idiopathic macular
      holes (MH). METHODS: A prospective analysis was performed of patients who had
      undergone surgical treatment for MH. Best-corrected visual acuity (BCVA) and
      optical coherence tomography (OCT) parameters including CRT, minimum and base
      diameters of the MHs were analyzed pre- and postoperatively. The relationships
      between final visual outcome and the OCT parameters were examined by single and
      multiple regression analysis. RESULTS: Forty-one MHs cases were successfully
      closed postoperatively. BCVA gradually improved, and CRT decreased during the
      observation period following MH surgery. There were significant positive
      correlations between CRT at 1 month and visual acuity at 12 months after vitreous
      surgery (P < 0.0001). MH diameter was positively correlated with CRT at 1 month
      after surgery and negatively with postoperative visual acuity. CONCLUSIONS: CRT
      at 1 month after MH surgery was related to preoperative MH diameter and visual
      acuity at 12 months postoperatively. Our data suggest that the increased CRT at
      the early postoperative period may result in better visual prognosis.

PMID- 26314746
TI  - The use of augmented auditory feedback to improve arm reaching in stroke: a case
      series.
AB  - PURPOSE: After practice, augmented feedback is the most important factor that
      facilitates motor learning. We assess the potential effectiveness of two types of
      augmented auditory feedback on the re-learning of arm reaching in individuals
      with stroke: (a) real-time knowledge of performance (KP) feedback and (b)
      rhythmic cueing in the form of knowledge of results (KR) feedback. METHOD: Five
      participants with stroke underwent short-term practice, reaching with their
      affected arm with KP, KR and no feedback, on separate days. We assessed range of
      motion of the upper extremity (shoulder, elbow) and trunk, mean error and
      variability of the performed trajectory, and movement time, before and after
      training. RESULTS: All participants benefitted from practice with feedback,
      though the effects varied across participants and feedback type. In three
      participants, KP feedback increased elbow extension and reduced compensatory
      trunk flexion. In four participants, KR feedback reduced movement time taken to
      perform the reach. Of note, one participant benefitted mostly from KP feedback,
      which increased shoulder flexion and elbow extension, and decreased compensatory
      trunk flexion and mean error. CONCLUSIONS: Within day practice with augmented
      auditory feedback improves reaching in individuals with stroke. This warrants
      further investigation with longer practice periods in a larger sample size.
      IMPLICATIONS FOR REHABILITATION: After practice, augmented feedback is the second
      most important factor that facilitates motor learning. Music-based augmented
      auditory feedback has potential to enhance reaching abilities in individuals with
      stroke. Future studies are warranted to evaluate the long-term effectiveness of
      this feedback over a longer training period in a larger sample size.

PMID- 26314747
TI  - Genomic expression program of Saccharomyces cerevisiae along a mixed-culture wine
      fermentation with Hanseniaspora guilliermondii.
AB  - BACKGROUND: The introduction of yeast starter cultures consisting in a blend of
      Saccharomyces cerevisiae and non-Saccharomyces yeast strains is emerging for
      production of wines with improved complexity of flavor. The rational use of this
      approach is, however, dependent on knowing the impact that co-inoculation has in
      the physiology of S. cerevisiae. In this work the transcriptome of S. cerevisiae
      was monitored throughout a wine fermentation, carried out in single culture or in
      a consortium with Hanseniaspora guilliermondii, this being the first time that
      this relevant yeast-yeast interaction is examined at a genomic scale. RESULTS: Co
      inoculation with H. guilliermondii reduced the overall genome-wide
      transcriptional response of S. cerevisiae throughout the fermentation, which was
      attributable to a lower fermentative activity of S. cerevisiae while in the mixed
      fermentation. Approximately 350 genes S. cerevisiae genes were found to be
      differently expressed (FDR < 0.05) in response to the presence of H.
      guilliermondii in the fermentation medium. Genes involved in biosynthesis of
      vitamins were enriched among those up-regulated in the mixed-culture
      fermentation, while genes related with the uptake and biosynthesis of amino acids
      were enriched among those more expressed in the single-culture. The differences
      in the aromatic profiles of wines obtained in the single and in the mixed
      fermentations correlated with the differential expression of S. cerevisiae genes
      encoding enzymes required for formation of aroma compounds. CONCLUSIONS: By
      integrating results obtained in the transcriptomic analysis performed with
      physiological data our study provided, for the first time, an integrated view
      into the adaptive responses of S. cerevisiae to the challenging environment of
      mixed culture fermentation. The availability of nutrients, in particular, of
      nitrogen and vitamins, stands out as a factor that may determine population
      dynamics, fermentative activity and by-product formation.

PMID- 26314748
TI  - Framing overdiagnosis in breast screening: a qualitative study with Australian
      experts.
AB  - BACKGROUND: The purpose of this study was to identify how the topic of
      overdiagnosis in breast cancer screening is framed by experts and to clarify
      differences and similarities within these frames in terms of problems, causes,
      values and solutions. METHODS: We used a qualitative methodology using interviews
      with breast screening experts across Australia and applying framing theory to map
      and analyse their views about overdiagnosis. We interviewed 33 breast screening
      experts who influence the public and/or policy makers via one or more of: public
      or academic commentary; senior service management; government advisory bodies;
      professional committees; non-government/consumer organisations. Experts were
      currently or previously working in breast screening in a variety of roles
      including clinical practice, research, service provision and policy, consumer
      representation and advocacy. RESULTS: Each expert used one or more of six frames
      to conceptualise overdiagnosis in breast screening. Frames are described as:
      Overdiagnosis is harming women; Stop squabbling in public; Don't hide the problem
      from women; We need to know the overdiagnosis rate; Balancing harms and benefits
      is a personal matter; and The problem is overtreatment. Each frame contains a
      different but internally coherent account of what the problem is, the causes and
      solutions, and a moral evaluation. Some of the frames are at least partly
      commensurable with each other; others are strongly incommensurable. CONCLUSIONS:
      Experts have very different ways of framing overdiagnosis in breast screening.
      This variation may contribute to the ongoing controversy in this topic. The
      concept of experts using different frames when thinking and talking about
      overdiagnosis might be a useful tool for those who are trying to negotiate the
      complexity of expert disagreement in order to participate in decisions about
      screening.

PMID- 26314749
TI  - Robotic-assisted kidney transplantation: our first case.
AB  - PURPOSE: Kidney transplantation is the preferred treatment for patients with end
      stage renal disease. In order to reduce the morbidity of the open surgery, a
      robotic-assisted approach has been recently introduced. According to the
      published literature, the robotic surgery allows the performance of kidney
      transplantation under optimal operative conditions while maintaining the safety
      and the functional results of the open approach. METHODS: We present the case of
      a mother donating to her daughter affected by end-stage renal disease (ESRD) due
      to Alport disease (creatinine: 353 umol/l; GFR: 13 ml/min per 1.73 m(2)).
      RESULTS: A robotic-assisted kidney transplant (RAKT) was successfully performed.
      Surgical time was 120 min with 53 min for vascular suture. The estimated blood
      loss was <50 cc. The kidney started to produce urine intra-operatively with a
      rate of 250 cc/h, which remained constant over the next hours. During the first
      postoperative day, the patient was ambulating and started oral intake. Pain was
      minimal, and no analgesia was required after 48 h. Serum creatinine improved
      progressively to 89 umol/l on postoperative day 3. No surgical complications were
      recorded, and the patient was sent home on postoperative day 5. CONCLUSION: We
      present the first Spanish transperitoneal pure RAKT from a living-related donor.
      We believe this is the second pure robotic-assisted kidney transplantation case
      performed in Europe. We believe that the potential advantages of RAKT are related
      to the quality of the vascular anastomosis, the possible lower complication rate
      and the shorter recovery of the recipients.

PMID- 26314750
TI  - Tongue-tie division to treat breastfeeding difficulties: our experience.
AB  - OBJECTIVES: To assess the benefits of frenotomy on breastfeeding in infants, and
      determine the influence of age. METHODS: A telephone questionnaire of all
      patients diagnosed with tongue-tie over 12 months was conducted pre-intervention
      and 1-month post-intervention. The Infant Breastfeeding Assessment Tool was used
      to assess breastfeeding. RESULTS: Of 54 infants diagnosed with tongue-tie, 78 per
      cent of mothers participated in the survey. Eighty-six per cent of patients
      underwent frenotomy, with no surgical complications. In the frenotomy group, 81
      per cent of mothers reported improvement in breastfeeding, versus 17 per cent in
      the non-surgical group (p = 0.0074). In the frenotomy group, the mean (+/
      standard deviation) Infant Breastfeeding Assessment Tool score was 3.33 +/- 1.51
      pre-intervention, versus 9.19 +/- 2.44 post-intervention (p = 0.0001). In the non
      surgical intervention group, the mean score (+/-standard deviation) was 4.17 +/-
      0.75 pre-intervention, versus 6.00 +/- 1.73 post-intervention (p = 0.16). For
      infants who underwent frenotomy, there was a reported improvement in 94 per cent
      of those aged less than 30 days, versus 68 per cent in infants aged over 30 days
      (p = 0.092). CONCLUSION: Frenotomy is a safe, short procedure that improves
      breastfeeding outcomes, and is best performed at an early age.

PMID- 26314751
TI  - The risk of neoplasm associated with dysgenetic testes in prepubertal and
      pubertal/adult patients.
AB  - INTRODUCTION: In patients with Y-chromosome in the karyotype, partial gonadal
      dysgenesis and disorders of male reproductive sex organs development are usually
      resected in childhood because of the high risk of germ cell tumours (GCT). In
      patients with Y-chromosome, complete gonadal dysgenesis and female genitalia
      gonadectomy is performed markedly later. However, due to the relatively low
      number of adult patients with preserved dysgenetic gonads, the true risk of
      neoplasm is unknown. The aim of the study was to evaluate the prevalence of
      neoplasia in dysgenetic gonads of children and adults with Y-chromosome in a
      retrospective study. MATERIAL AND METHODS: A review of medical documentation of
      94 patients with disorders of sex development (DSD), Y-chromosome and gonadal
      dysgenesis (GD), aged 1.2-32 years (47 prepubertal, 1.2-10 years; 47
      pubertal/adult, 13-32 years), was conducted. Serum levels of follicle-stimulating
      hormone (FSH), luteinizing hormone (LH) and testosterone were determined.
      Bilateral gonadectomy was performed in 73.4% of patients, and unilateral
      gonadectomy with biopsy of the contralateral gonad in 26.4%. All gonadal tissues
      were subjected to immunohistochemical evaluation with antibodies against PLAP and
      OCT3/4 (markers of malignant germ cells, but also foetal multipotent germ cells),
      while gonads of prepubertal patients were examined by c-KIT, as well. RESULTS:
      Streak gonads were identified on both sides (complete GD) in 30.8%, a streak
      gonad on one side and an underdeveloped testis on the other (asymmetric GD) in
      38.3%, and underdeveloped testicular structure on both sides (partial GD) in
      30.8% of cases. Germ cell neoplasia was found in 53.2% of patients (51.1% in
      children, 55.3% in pubertal/adults). Invasive GCT were identified in 11.7% of
      cases, of which 90.9% were in pubertal/adult patients. Other neoplastic lesions
      included gonadoblastoma (16% prevalence) and testicular carcinoma in situ
      (25.5%). In younger patients FSH serum levels were increased in 81% of cases
      (mean 2.82 +/- 2.18 IU/L), while LH in 58% (mean 1.82 +/- 1.69 IU/L).
      Hypergonadotropic hypogonadism was diagnosed in most of the pubertal/ /adult
      patients (mean FSH 54.2 +/- 23.3 IU/L, mean LH 21.7 +/- 12.1 IU/L, mean
      testosterone 5.5 +/- 4.5 nmol/L). CONCLUSIONS: Dysgenetic gonads in patients with
      Y chromosome have a high risk of germ cell neoplasia (ca. 50%). If they are
      preserved until puberty/early adulthood, they may develop overt, invasive GCT.
      The gonads also have poor hormonal activity (hypergonadotropic hypogonadism) in
      most of the pubertal/adult patients. Each of these cases must be considered
      individually and a decision to remove the gonad or not should be based on the
      comprehensive analysis of the phenotype by a multidisciplinary team of
      specialists in consultation with the patient and the parents. If dysgenetic
      gonads are not resected in childhood, these patients need careful ongoing follow
      up examination, including biopsy and histopathological evaluation.

PMID- 26314752
TI  - Should a standard lymphadenectomy during pancreatoduodenectomy exclude para
      aortic lymph nodes for all cases of resectable pancreatic head cancer? A
      consensus statement by the Chinese Study Group for Pancreatic Cancer (CSPAC).
AB  - Understanding and formulating an appropriate strategy for the para-aortic lymph
      nodes (LN16) during curative surgery for pancreatic head cancer have been
      controversial for some time. This study intended to provide a recommendation for
      surgeons to perform an optimal curative surgery on pancreatic cancer patients
      with or without LN16 involvement. Based on an updated literature search and
      review, the members of the Chinese Study Group for Pancreatic Cancer (CSPAC) from
      high-volume centers reached a consensus on the issue of LN16 in pancreatic head
      cancer. Metastasis to LN16 is quite common in pancreatic head cancer cases.
      Depending on the location of the tumor, including the ventral and dorsal
      pancreas, there could be various lymph node drainage pathways whereby LN16 does
      not necessarily belong to the Group 3 lymph node stations for all cases of
      pancreatic head cancer. Although LN16 involvement generally indicates a poor
      prognosis, some cohorts of LN16-involved cases have benefited from a curative
      surgery, and there is still a lack of level I evidence to convince surgeons to
      abandon all resectable cases with LN16 positivity. Resection of LN16 combined
      with a standard lymphadenectomy during pancreatoduodenectomy is recommended by
      CSPAC, except in patients with both positive LN16 and criteria based on: i) the
      resectability status of primary tumor; ii) the extent of involved para-aortic
      lymph nodes; and iii) the serum tumor burden assessed preoperatively.

PMID- 26314753
TI  - Clarifying some findings regarding the ventriloquist aftereffect.

PMID- 26314754
TI  - Assessing the effects of physical and perceived luminance contrast on RT and TMS
      induced percepts.
AB  - Simple reaction times (RTs) are inversely related to the luminance of a visual
      region, with RT increasing as luminance decreases, and decreasing as luminance
      increases. A potential discrepancy in the link between luminance and RT, however,
      stems from the perception of luminance itself. Here, we tested whether RT is
      modulated by a measureable amount of light (luminance) or perceptual amount of
      light (brightness), as two test regions having the same luminance can be
      perceived as having different brightness. The current study investigates the
      effects of brightness using probes and artificial percepts, i.e., transcranial
      magnetic stimulation (TMS)-induced light and dark percepts. In Experiment 1,
      participants performed a RT task to light and dark probes presented over two
      backgrounds, one exhibiting a physical luminance and the other exhibiting
      perceptual brightness. Experiment 2 tested whether perceptual brightness could
      influence RT and frequency of artificial percepts. We found that while brightness
      contrast modulated RT to the dark probes, the frequency of artificial percepts
      was susceptible to both physical and perceived changes in luminance. These data
      suggest that some behavioral responses can be influenced by an illusion of
      brightness, wherein there is no actual change in luminance, as well as the
      perception of TMS-induced percepts. 

PMID- 26314755
TI  - Position shifts of fMRI-based population receptive fields in human visual cortex
      induced by Ponzo illusion.
AB  - Ponzo illusion is a well-known perceptual phenomenon in which the perceived sizes
      of visual objects are altered by visual depth cues created by converging lines at
      the horizon. One possible neural mechanism of the Ponzo illusion is the receptive
      field position shifts of V1 neurons, as supported by a recent monkey
      electrophysiological study (Ni et al. in Curr Biol 24(14):1653-1658, 2014). Here,
      we used fMRI-based population receptive field (pRF) mapping technique in
      combination of psychophysics to investigate this idea. We found that, relative to
      the close apparent depth in a 3D scene, the far apparent depth in the scene
      caused the pRF positions of voxels in V1-V3 to shift toward the fovea, in line
      with subjects' percept of the Ponzo illusion. Moreover, the pRF position shift in
      V1 significantly correlated with the magnitude of the Ponzo illusion across
      individual subjects. Our findings thus provide evidence for the close association
      between the perceived object size and the pRF position shift in human visual
      areas, especially in V1, lending further support for the receptive field position
      shift explanation for the Ponzo illusion. 

PMID- 26314756
TI  - Building chessboard-like supramolecular structures on Au(111) surfaces.
AB  - We investigate an anthracene derivative, 3(5)-(9-anthryl) pyrazole (ANP), self
      assembled on the Au(111) surface by means of scanning tunneling microscopy (STM)
      and density functional theory (DFT) calculations. A chessboard-like network
      structure composed of ANP molecules is found, covering the whole Au(111)
      substrate. Our STM results and DFT calculations reveal that the formation of
      chessboard-like networks originates from a basic unit cell, a tetramer structure,
      which is formed by four ANP molecules connected through C-H...N hydrogen bonds.
      The hydrogen bonds inside each tetramer and the molecule-substrate interaction
      are fundamentally important in providing a driving force for formation of the
      supramolecular networks. 

PMID- 26314757
TI  - Comparative inhibitory effect of prenylated coumarins, ferulenol and ferprenin,
      contained in the 'poisonous chemotype' of Ferula communis on mammal liver
      microsomal VKORC1 activity.
AB  - Two distinguishable chemotypes of Ferula communis have been described: the
      'nonpoisonous' chemotype, containing as main constituents the daucane esters; and
      the 'poisonous' chemotype containing prenylated coumarins, such as ferulenol and
      ferprenin. Ferulenol and ferprenin are 4-oxygenated molecules such as dicoumarol
      and warfarin, the first developed antivitamin K molecules. Antivitamin K
      molecules specifically inhibit VKORC1, an enzyme essential for recycling vitamin
      K. This latest is involved in the activation of clotting factors II, VII, IX, X.
      The inhibiting effect of ferulenol on VKORC1 was shown in rat, but not for
      species exposed to F. communis while in vivo studies suggest differences between
      animal susceptibility to ferulenol. The inhibiting effect of ferprenin on VKORC1
      was never demonstrated. The aim of this study was to compare the inhibiting
      effect of both compounds on VKORC1 of different species exposed to F. communis.
      Vitamin K epoxide activity was evaluated for each species from liver microsomes
      and inhibiting effect of ferulenol and ferprenin was characterized. Ferulenol and
      ferprenin were shown to be able to inhibit VKORC1 from all analyzed species.
      Nevertheless, susceptibility to ferulenol and ferprenin presented differences
      between species, suggesting a different susceptibility to 'poisonous' chemotypes
      of F. communis. 

PMID- 26314758
TI  - Myocardial edema in Takotsubo syndrome mimicking apical hypertrophic
      cardiomyopathy: An insight into diagnosis by cardiovascular magnetic resonance.
AB  - Myocardial edema is one of the characteristic features in the pathogenesis of
      Takotsubo syndrome. We report a middle aged man who presented with typical
      clinical and echocardiographic features of apical variant of Takotsubo syndrome.
      However, a cardiovascular magnetic resonance study performed 10 days after
      presentation did not show any apical 'ballooning' but revealed features of an
      apical hypertrophic cardiomyopathy on cine images. Tissue characterization with
      T2 weighted images proved severe edema as the cause of significantly increased
      apical wall thickness. A follow-up cardiovascular magnetic resonance study was
      performed 5 months later which showed that edema, wall thickening and the
      appearance of apical hypertrophic cardiomyopathy all resolved, confirming
      Takotsubo syndrome as the cause of the initial appearance. As the affected
      myocardium most commonly involves the apical segments, an edema induced increase
      in apical wall thickness may lead to appearances of an apical hypertrophic
      cardiomyopathy rather than apical ballooning in the acute to subacute phase of
      Takotsubo syndrome. 

PMID- 26314759
TI  - Investigating the link between disease activity and infliximab serum levels in
      rheumatoid arthritis patients.
AB  - OBJECTIVES: The aim of this study was to examine the extent to which infliximab
      (IFX) serum levels impact disease activity in rheumatoid arthritis (RA) patients.
      METHODS: In this cross sectional study, serum samples were taken prior to drug
      infusion from 60 RA patients who had been undergoing IFX therapy > 12 months as a
      first line of biological treatment. Patient IFX levels were tested and then
      associated with clinical disease activity. Three DAS28 cut-off points, <2.6, <3.2
      and <5.1 were used to determine whether detectable IFX levels were any predictor
      of clinical disease activity. Logistic regression analysis was run to check other
      possible factors associated with RA clinical outcomes such as MTX concomitant
      use, CRP and ESR. RESULTS: Sixteen (27%) out of the 60 patients tested negative;
      28 (46%) presented subtherapeutic and 16 (27%) therapeutic IFX levels. Median IFX
      levels were higher in patients either in remission or showing low disease
      activity than in those with moderate and high disease activity (p=0.014).
      Significant association was found between IFX levels and clinical disease
      activity (p=0.001). Detectable levels of IFX shows better sensitivity and
      specificity to identify patients with DAS28<3.2 than to identify patients with
      DAS28<2.6 or DAS28<5.1. Conversely, the best DAS28 cut-off to identify
      detectable/undetectable IFX was 3.19, with AUC under ROC curve 0.804 (Sd.E
      0.070), 76% specificity and 83% sensitivity (p<0.001). MTX use, CRP and ESR did
      not interfere with this association. Seven out of the 8 patients with anti-IFX
      antibodies presented DAS28>3.2 (p=0.005). CONCLUSIONS: DAS28 and IFX serum levels
      were shown to have an inverse correlation. Undetectable IFX serum levels were
      associated to RA patients presenting DAS28>3.2 meaning that DAS28 <3.2 may be
      useful to clinicians to evaluate patient response to drug therapy.

PMID- 26314760
TI  - Experimental treatments of endometriosis.
AB  - Endometriosis is defined as the presence of endometrial gland and stroma outside
      the uterine cavity. It is an estrogen-dependent disease and is associated with
      chronic pelvic pain, dysmenorrhea, dyspareunia and infertility. The treatment of
      endometriosis is conservative or radical surgery, medical therapies or their
      combination. All currently used hormonally active treatments are effective in the
      treatment of endometriosis; however, the adverse effects of these hormonal
      treatments limit their long-term use. Moreover, recurrence rates are high after
      cessation of therapy, and the treatments have no benefit in endometriosis
      associated infertility. Therefore, researchers are working on new treatment
      modalities with improved side effects, mainly focusing on the molecular targets
      involved in etiopathogenesis of endometriosis. Here we summarized these novel
      treatments modalities. 

PMID- 26314761
TI  - Spontaneous dehydrocoupling in peri-substituted phosphine-borane adducts.
AB  - Bis(borane) adducts Acenap(PiPr2.BH3)(PRH.BH3) (Acenap = acenaphthene-5,6-diyl;
      4a, R = Ph; 4b, R = ferrocenyl, Fc; 4c, R = H) were synthesised by the reaction
      of excess H3B.SMe2 with either phosphino-phosphonium salts
      [Acenap(PiPr2)(PR)](+)Cl(-) (1a, R = Ph; 1b, R = Fc), or bis(phosphine)
      Acenap(PiPr2)(PH2) (3). Bis(borane) adducts 4a-c were found to undergo dihydrogen
      elimination at room temperature, this spontaneous catalyst-free phosphine-borane
      dehydrocoupling yields BH2 bridged species Acenap(PiPr2)(MU-BH2)(PR.BH3) (5a, R =
      Ph; 5b, R = Fc; 5c, R = H). Thermolysis of 5c results in loss of the terminal
      borane moiety to afford Acenap(PiPr2)(MU-BH2)(PH) (14). Single crystal X-ray
      structures of 3, 4b and 5a-c are reported. 

PMID- 26314762
TI  - DNA methylation of CiRIG-I gene notably relates to the resistance against GCRV
      and negatively-regulates mRNA expression in grass carp, Ctenopharyngodon idella.
AB  - Retinoic acid-inducible gene I (RIG-I), a crucial member of cytoplasmic pattern
      recognition receptors (PRRs), is initially characterized as a dsRNA-binding
      protein triggering interferon (IFN) induction in response to virus invasion.
      While the antiviral regulatory mechanism of RIG-I remains largely unclear. In
      this study, the mechanism of CiRIG-I (Ctenopharyngodon idella RIG-I) against
      grass carp reovirus (GCRV) would be revealed from the perspective of epigenetics.
      By prediction, three CpG islands (CGIs) were located in 5'-flanking region and
      the first exon. The first CGI and the second one, both located in the 5'-flanking
      region, were 109 base pairs (bp) and 134bp in length, involving five CpG sites
      and four loci, respectively. The third CGI was of 386bp spanning the 5'-flanking
      region and the first exon, densely possessing 24 CpG sites. DNA methylation
      statuses of CpG sites were identified by virtue of the bisulfite sequencing PCR
      (BSP) in spleen of all susceptible and resistant individuals post the challenge
      experiment. The resistance association analysis was performed with Chi-square
      test. And the relationship between DNA methylation and gene expression in CiRIG-I
      was investigated by quantitative real-time RT-PCR (qRT-PCR). Results indicated
      only the methylation of -534 CpG site in the second CGI possessing tight
      association with the resistance against GCRV, which was significantly higher in
      the susceptible individuals than that in the resistant individuals. In addition,
      the average expression of CiRIG-I was down-regulated in the susceptible group
      compared with the resistant one demonstrating gene transcription may be
      negatively-regulated by DNA methylation in CiRIG-I. Collectively, the methylation
      statuses of CiRIG-I were extremely related to the resistance against GCRV and
      maybe serve as a negative modulator on antiviral transcription of CiRIG-I. This
      study revealed the underlying antiviral regulatory mechanism of CiRIG-I and laid
      a theoretical foundation for the nosogenesis of hemorragic diseases in C. idella.

PMID- 26314763
TI  - Generation of cancer-specific CD8(+) CD69(+) cells inhibits colon cancer growth.
AB  - The therapy of colon cancer (Cca) is poor currently. The abnormality of immune
      function is recognized in cancer-bearing hosts. This study aims to inhibit Cca
      growth with the in vivo induction of Cca-specific CD8(+) CD69(+) T cell
      polarization. In this study, a mouse tumor model was created with a mouse colon
      cancer (Cca) cell line. The Cca-bearing mice were immunized with Cca extracts and
      alum (using as an adjuvant). The CD8(+) CD69(+) cell polarization status was
      analyzed by flow cytometry and enzyme-linked immunosorbent assay. The results
      showed that a Cca antigen-specific CD8(+) CD69(+) cells were induced in the Cca
      bearing mice. The Cca growth was efficiently inhibited by the Cca-specific CD8(+)
      CD69(+) cell response. The Cca-specific CD8(+) CD69(+) cells were detected in the
      Cca mass and spleen, which had the ability to induce Cca cell apoptosis. In
      conclusion, the Cca-specific CD8(+) CD69(+) cell polarization can be induced in
      Cca-bearing mice, which can efficiently inhibit the Cca growth.

PMID- 26314764
TI  - Single Shot Polarization Characterization of XUV FEL Pulses from Crossed
      Polarized Undulators.
AB  - Polarization control is a key feature of light generated by short-wavelength free
      electron lasers. In this work, we report the first experimental characterization
      of the polarization properties of an extreme ultraviolet high gain free-electron
      laser operated with crossed polarized undulators. We investigate the average
      degree of polarization and the shot-to-shot stability and we analyze aspects such
      as existing possibilities for controlling and switching the polarization state of
      the emitted light. The results are in agreement with predictions based on
      Gaussian beams propagation. 

PMID- 26314766
TI  - Corrigendum.

PMID- 26314765
TI  - Extracting biomolecule collision cross sections from the high-resolution FT-ICR
      mass spectral linewidths.
AB  - It is known that the ion collision cross section (CCS) may be calculated from the
      linewidth of a Fourier transform ion cyclotron resonance (FT-ICR) mass spectral
      peak at elevated pressure (e.g., ~10(-6) Torr). However, the high mass resolution
      of FT-ICR is sacrificed in those experiments due to high buffer gas pressure. In
      this study, we describe a linewidth correction method to eliminate the windowing
      induced peak broadening effect. Together with the energetic ion-neutral collision
      model previously developed by our group, this method enables the extraction of
      CCSs of biomolecules from high-resolution FT-ICR mass spectral linewidths,
      obtained at a typical operating buffer gas pressure of modern FT-ICR instruments
      (~10(-10) Torr). CCS values of peptides including MRFA, angiotensin I, and
      bradykinin measured by the proposed method agree well with ion mobility
      measurements, and the unfolding of protein ions (ubiquitin) at higher charge
      states is also observed. 

PMID- 26314767
TI  - Core clock, SUB1, and ABAR genes mediate flooding and drought responses via
      alternative splicing in soybean.
AB  - Circadian clocks are a great evolutionary innovation and provide competitive
      advantage during the day/night cycle and under changing environmental conditions.
      The circadian clock mediates expression of a large proportion of genes in plants,
      achieving a harmonious relationship between energy metabolism, photosynthesis,
      and biotic and abiotic stress responses. Here it is shown that multiple
      paralogues of clock genes are present in soybean (Glycine max) and mediate
      flooding and drought responses. Differential expression of many clock and SUB1
      genes was found under flooding and drought conditions. Furthermore, natural
      variation in the amplitude and phase shifts in PRR7 and TOC1 genes was also
      discovered under drought and flooding conditions, respectively. PRR3 exhibited
      flooding- and drought-specific splicing patterns and may work in concert with
      PRR7 and TOC1 to achieve energy homeostasis under flooding and drought
      conditions. Higher expression of TOC1 also coincides with elevated levels of
      abscisic acid (ABA) and variation in glucose levels in the morning and afternoon,
      indicating that this response to abiotic stress is mediated by ABA, endogenous
      sugar levels, and the circadian clock to fine-tune photosynthesis and energy
      utilization under stress conditions. It is proposed that the presence of multiple
      clock gene paralogues with variation in DNA sequence, phase, and period could be
      used to screen exotic germplasm to find sources for drought and flooding
      tolerance. Furthermore, fine tuning of multiple clock gene paralogues (via a
      genetic engineering approach) should also facilitate the development of flooding-
      and drought-tolerant soybean varieties.

PMID- 26314768
TI  - Transient hypothyroidism associated with viral Human Parechovirus encephalitis in
      a newborn.
AB  - Human Parechovirus type 3 (HPeV-3) is a neurotropic virus which can cause
      neonatal encephalitis, presenting as encephalopathy with seizures and diffuse
      white matter lesions on brain imaging. Neurodevelopmental outcome is linked to
      the extent of white matter abnormalities. We report on a neonate with clinical
      and biochemical findings of transient central hypothyroidism associated with HPeV
      3 encephalitis. The co-occurrence of transient hypothyroidism and viral
      encephalitis has not been reported in newborns before. Transient suppression of
      the hypothalamo-pituitary-thyroidal axis is described in critically ill babies as
      the nonthyroidal-illness syndrome. Assessment of thyroid function in neonatal
      cases of HPeV-3 infection is required to conclude whether a transient
      hypothyroidism as in nonthyroidal-illness syndrome may be triggered by viral
      meningo-encephalitis and if treatment may influence neurodevelopmental outcome. 

PMID- 26314771
TI  - The ESMO guideline strategy: an identity statement and reflections on
      improvement.
AB  - Guidelines should provide recommendations on the optimal management of a patient
      in specific clinical circumstances based on the scientific evidence. ESMO, as
      Europe's leading society in medical oncology produces a range of guideline
      products in order to assist the cancer specialist towards implementation of
      quality cancer care, as well as in order to provide information to patients
      establishing standards for up-to-date optimal management. The ESMO 'guideline
      products' include the Clinical Practice Guidelines, the complementing Consensus
      Conferences on focused clinical scenarios, as well as memory tools such as print
      and e-Pocket Guidelines and Patient Guides. In this manuscript, methodology,
      design and characteristics of the ESMO guideline products are explained and
      discussed by their strengths and weaknesses, opportunities and threats in order
      to stimulate reflections on room for improvement and future strategy. 

PMID- 26314772
TI  - Peripheral T-cell lymphomas: ESMO Clinical Practice Guidelines for diagnosis,
      treatment and follow-up.

PMID- 26314773
TI  - Diffuse large B-cell lymphoma (DLBCL): ESMO Clinical Practice Guidelines for
      diagnosis, treatment and follow-up.

PMID- 26314774
TI  - Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment
      and follow-up.

PMID- 26314775
TI  - Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis,
      treatment and follow-up.

PMID- 26314776
TI  - Central venous access in oncology: ESMO Clinical Practice Guidelines.

PMID- 26314777
TI  - Treatment of dyspnoea in advanced cancer patients: ESMO Clinical Practice
      Guidelines.

PMID- 26314779
TI  - Thymic epithelial tumours: ESMO Clinical Practice Guidelines for diagnosis,
      treatment and follow-up.

PMID- 26314780
TI  - Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis,
      treatment and follow-up.

PMID- 26314781
TI  - Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis,
      treatment and follow-up.

PMID- 26314782
TI  - Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment
      and follow-up.

PMID- 26314783
TI  - An appraisal of theoretical approaches to examining behaviours in relation to
      Human Papillomavirus (HPV) vaccination of young women.
AB  - BACKGROUND: Interventions to increase uptake of Human Papillomavirus (HPV)
      vaccination by young women may be more effective if they are underpinned by an
      appropriate theoretical model or framework. The aims of this review were: to
      describe the theoretical models or frameworks used to explain behaviours in
      relation to HPV vaccination of young women, and: to consider the appropriateness
      of the theoretical models or frameworks used for informing the development of
      interventions to increase uptake. METHODS: Primary studies were identified
      through a comprehensive search of databases from inception to December 2013.
      RESULTS: Thirty-four relevant studies were identified, of which 31 incorporated
      psychological health behaviour models or frameworks and three used socio-cultural
      models or theories. The primary studies used a variety of approaches to measure a
      diverse range of outcomes in relation to behaviours of professionals, parents,
      and young women. The majority appeared to use theory appropriately throughout.
      About half of the quantitative studies presented data in relation to goodness of
      fit tests and the proportion of the variability in the data. CONCLUSION: Due to
      diverse approaches and inconsistent findings across studies, the current
      contribution of theory to understanding and promoting HPV vaccination uptake is
      difficult to assess. Ecological frameworks encourage the integration of
      individual and social approaches by encouraging exploration of the intrapersonal,
      interpersonal, organisational, community and policy levels when examining public
      health issues. Given the small number of studies using such approach, combined
      with the importance of these factors in predicting behaviour, more research in
      this area is warranted.

PMID- 26314784
TI  - Hybrid glasses from strong and fragile metal-organic framework liquids.
AB  - Hybrid glasses connect the emerging field of metal-organic frameworks (MOFs) with
      the glass formation, amorphization and melting processes of these chemically
      versatile systems. Though inorganic zeolites collapse around the glass transition
      and melt at higher temperatures, the relationship between amorphization and
      melting has so far not been investigated. Here we show how heating MOFs of
      zeolitic topology first results in a low density 'perfect' glass, similar to
      those formed in ice, silicon and disaccharides. This order-order transition leads
      to a super-strong liquid of low fragility that dynamically controls collapse,
      before a subsequent order-disorder transition, which creates a more fragile high
      density liquid. After crystallization to a dense phase, which can be remelted,
      subsequent quenching results in a bulk glass, virtually identical to the high
      density phase. We provide evidence that the wide-ranging melting temperatures of
      zeolitic MOFs are related to their network topologies and opens up the
      possibility of 'melt-casting' MOF glasses. 

PMID- 26314785
TI  - Possible involvement of TRPV1 and TRPV4 in nociceptive stimulation- induced
      nocifensive behavior and neuroendocrine response in mice.
AB  - Members of the transient receptor potential (TRP) family of ion channels play
      important roles in inflammation and pain. Here, we showed that both TRPV1 and
      TRPV4 might contribute to biphasic nocifensive behavior and neuroendocrine
      response following a formalin test. We subcutaneously injected saline, formalin,
      or the TRPV4 agonist, 4alpha-phorbol 12,13-didecanoate (4alpha-PDD) into one
      hindpaw of wild-type (WT), TRPV1-deficient (Trpv1(-/-)), and TRPV4-deficient
      (Trpv4(-/-)) mice to investigate nocifensive behaviors (phase I [0-10 min] and
      phase II [10-60 min]) and Fos expression in the dorsal horn of the spinal cord
      and other brain regions related to pain, in the paraventricular nucleus (PVN),
      paraventricular nucleus of the thalamus, the medial habenular nucleus, the medial
      nucleus of the amygdala and capsular part of the central amygdala. Subcutaneous
      (s.c.) injection of formalin caused less nocifensive behavior in Trpv1(-/-) and
      Trpv4(-/-) mice than in WT mice during phase I. In phase II, however, formalin
      induced less nocifensive behavior only in the Trpv1(-/-) mice, but not in the
      Trpv4(-/-) mice, relative to WT mice. The number of Fos-like immunoreactive (LI)
      neurons in laminae I-II of the dorsal horn increased in all types of mice 90 min
      after s.c. injection of formalin; however, there was no difference in the other
      regions between saline- and formalin-treated mice. Furthermore, s.c. injection of
      4alpha-PDD did not induce nociceptive behavior nor influence the number of Fos-LI
      neurons in the all above mentioned regions in any of the mice. These results
      suggest that TRPV4-mediated nociceptive information from the peripheral tissue
      excluding the spinal pathway might be involved the formalin behavioral response
      during phase I. Only TRPV1 might regulate the formalin behavioral response in
      peripheral neuron.

PMID- 26314786
TI  - Hydrogel Walkers with Electro-Driven Motility for Cargo Transport.
AB  - In this study, soft hydrogel walkers with electro-driven motility for cargo
      transport have been developed via a facile mould-assisted strategy. The hydrogel
      walkers consisting of polyanionic poly(2-acrylamido-2-methylpropanesulfonic acid
      co-acrylamide) exhibit an arc looper-like shape with two "legs" for walking. The
      hydrogel walkers can reversibly bend and stretch via repeated "on/off" electro
      triggers in electrolyte solution. Based on such bending/stretching behaviors, the
      hydrogel walkers can move their two "legs" to achieve one-directional walking
      motion on a rough surface via repeated "on/off" electro-triggering cycles.
      Moreover, the hydrogel walkers loaded with very heavy cargo also exhibit
      excellent walking motion for cargo transport. Such hydrogel systems create new
      opportunities for developing electro-controlled soft systems with simple
      design/fabrication strategies in the soft robotic field for remote manipulation
      and transportation. 

PMID- 26314787
TI  - Health and quality of life among survivors of testis cancer.

PMID- 26314789
TI  - Characterization of a highly sensitive and selective novel trapping reagent,
      stable isotope labeled glutathione ethyl ester, for the detection of reactive
      metabolites.
AB  - INTRODUCTION: Glutathione (GSH) trapping assays are widely used to predict the
      post-marketing risk for idiosyncratic drug reactions (IDRs) in the pharmaceutical
      industry. Although several GSH derivatives have been introduced as trapping
      reagents for reactive intermediates, more sensitive and selective reagents are
      desired to prevent the generation of erroneous results. In this study, stable
      isotope labeled GSH ethyl ester (GSHEE-d5) was designed and its detection
      capability was evaluated. METHODS: GSHEE-d5 was synthesized and its detection
      potential was compared with stable isotope labeled GSH ([(13)C2,(15)N]GSH) as a
      reference trapping reagent. The trapping reagents were added to human liver
      microsomes as a 1:1 mixture with GSHEE or GSH, respectively, and incubated with
      seven IDR positive drugs and three IDR negative drugs. The adducts formed between
      the reagents and reactive metabolites were analyzed by unit resolution mass
      spectrometer (MS) using isotope pattern-dependent scan with neutral loss
      filtering. RESULTS: A single-step reaction of GSH and ethanol-d6 produced GSHEE
      d5 with a yield of 85%. The GSHEE-d5 assay detected adducts with all seven IDR
      positive drugs, and no adducts were detected with the three IDR negative drugs.
      In contrast, the [(13)C2,(15)N]GSH assay failed to detect adducts with three of
      the IDR positive drugs. In the case of diclofenac, the GSHEE-d5 assay showed a 4
      times greater signal intensity than the [(13)C2,(15)N]GSH assay. DISCUSSION:
      GSHEE-d5 enabled the detection of reactive metabolites with greater sensitivity
      and selectivity than [(13)C2,(15)N]GSH. These results demonstrate that GSHEE-d5
      would be a useful trapping reagent for evaluating the risk of IDRs with unit
      resolution MS.

PMID- 26314790
TI  - Radiotherapy after mastectomy for screen-detected ductal carcinoma in situ.
AB  - BACKGROUND: A role for radiotherapy after mastectomy for ductal carcinoma in situ
      (DCIS) is unclear. Using a prospective audit of DCIS detected through the NHS
      Breast Screening Programme we sought to determine a rationale for the use of post
      mastectomy radiotherapy for DCIS. METHODS: Over a nine year period, from 9972
      patients with screen-detected DCIS and complete surgical, pathology, radiotherapy
      and follow up data, 2944 women underwent mastectomy for DCIS of whom 33 (1.1%)
      received radiotherapy. RESULTS: Use of post mastectomy radiotherapy was
      significantly associated with a close (<1 mm) pathology margin (chi(2)(1) 95.81;
      p < 0.00001), DCIS size (chi(2) (3) 16.96; p < 0.001) and the presence of
      microinvasion (chi(2)(1) 3.92; p < 0.05). At a median follow up 61 months, no
      woman who received radiotherapy had an ipsilateral further event, and only 1/33
      women (3.0%) had a contralateral event. Of the women known not to have had
      radiotherapy post mastectomy, 45/2894 (1.6%) had an ipsilateral further event and
      83 (2.9%) had a contralateral event. CONCLUSION: Recurrence following mastectomy
      for DCIS is rare. A close (<1 mm) margin, large tumour size and microinvasion,
      may merit radiotherapy to reduce ipsilateral recurrence.

PMID- 26314791
TI  - Novel internally quenched substrate of the trypsin-like subunit of 20S eukaryotic
      proteasome.
AB  - This article describes the synthesis, using combinatorial chemistry, of
      internally quenched substrates of the trypsin-like subunit of human 20S
      proteasome. Such substrates were optimized in both the nonprime and prime regions
      of the peptide chain. Two were selected as the most susceptible for proteasomal
      proteolysis with excellent kinetic parameters: (i) ABZ-Val-Val-Ser-Arg-Ser-Leu
      Gly-Tyr(3-NO2)-NH2 (kcat/KM = 934,000 M(-1) s(-1)) and (ii) ABZ-Val-Val-Ser-GNF
      Ala-Met-Gly-Tyr(3-NO2)-NH2 (kcat/KM = 1,980,000 M(-1) s(-1)). Both compounds were
      efficiently hydrolyzed by the 20S proteasome at picomolar concentrations,
      demonstrating significant selectivity over other proteasome entities.

PMID- 26314788
TI  - 2016 Classification Criteria for Macrophage Activation Syndrome Complicating
      Systemic Juvenile Idiopathic Arthritis: A European League Against
      Rheumatism/American College of Rheumatology/Paediatric Rheumatology International
      Trials Organisation Collaborative Initiative.
AB  - OBJECTIVE: To develop criteria for the classification of macrophage activation
      syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (JIA).
      METHODS: A multistep process, based on a combination of expert consensus and
      analysis of real patient data, was conducted. A panel of 28 experts was first
      asked to classify 428 patient profiles as having or not having MAS, based on
      clinical and laboratory features at the time of disease onset. The 428 profiles
      comprised 161 patients with systemic JIA-associated MAS and 267 patients with a
      condition that could potentially be confused with MAS (active systemic JIA
      without evidence of MAS, or systemic infection). Next, the ability of candidate
      criteria to classify individual patients as having MAS or not having MAS was
      assessed by evaluating the agreement between the classification yielded using the
      criteria and the consensus classification of the experts. The final criteria were
      selected in a consensus conference. RESULTS: Experts achieved consensus on the
      classification of 391 of the 428 patient profiles (91.4%). A total of 982
      candidate criteria were tested statistically. The 37 best-performing criteria and
      8 criteria obtained from the literature were evaluated at the consensus
      conference. During the conference, 82% consensus among experts was reached on the
      final MAS classification criteria. In validation analyses, these criteria had a
      sensitivity of 0.73 and a specificity of 0.99. Agreement between the
      classification (MAS or not MAS) obtained using the criteria and the original
      diagnosis made by the treating physician was high (kappa = 0.76). CONCLUSION: We
      have developed a set of classification criteria for MAS complicating systemic JIA
      and provided preliminary evidence of its validity. Use of these criteria will
      potentially improve understanding of MAS in systemic JIA and enhance efforts to
      discover effective therapies, by ensuring appropriate patient enrollment in
      studies.

PMID- 26314792
TI  - iRNA-Methyl: Identifying N(6)-methyladenosine sites using pseudo nucleotide
      composition.
AB  - Occurring at adenine (A) with the consensus motif GAC, N(6)-methyladenosine
      (m(6)A) is one of the most abundant modifications in RNA, which plays very
      important roles in many biological processes. The nonuniform distribution of
      m(6)A sites across the genome implies that, for better understanding the
      regulatory mechanism of m(6)A, it is indispensable to characterize its sites in a
      genome-wide scope. Although a series of experimental technologies have been
      developed in this regard, they are both time-consuming and expensive. With the
      avalanche of RNA sequences generated in the postgenomic age, it is highly desired
      to develop computational methods to timely identify their m(6)A sites. In view of
      this, a predictor called "iRNA-Methyl" is proposed by formulating RNA sequences
      with the "pseudo dinucleotide composition" into which three RNA physiochemical
      properties were incorporated. Rigorous cross-validation tests have indicated that
      iRNA-Methyl holds very high potential to become a useful tool for genome
      analysis. For the convenience of most experimental scientists, a web-server for
      iRNA-Methyl has been established at http://lin.uestc.edu.cn/server/iRNA-Methyl by
      which users can easily get their desired results without needing to go through
      the mathematical details. 

PMID- 26314793
TI  - The 2015 ACR Commission on Human Resources Workforce Survey.
AB  - PURPOSE: The ACR Commission on Human Resources continues to conduct its annual
      electronic survey to better understand the present workforce scenario for
      radiologists. METHODS: The Practice of Radiology Environment Database was used to
      identify group leads, who were asked to complete an electronic survey developed
      by the Commission on Human Resources. The survey asked group leaders to report
      the number of radiologists they currently employ or supervise, the number hired
      in 2014, and the numbers they plan to hire in 2015 and 2018. The leaders were
      asked to report the subspecialty area used as the main reason for hiring each
      physician, as well as the ages and genders of their current workforce. RESULTS:
      Thirty-two percent of group leaders responded to the survey, corresponding to
      12,079 radiologists or 39% of all practicing radiologists. Twenty-one percent of
      the workforce is female and 79% is male. Ten percent of radiologists older than
      65 years are women, while 32% younger than 35 are women. Twelve percent of
      radiologists work part-time, corresponding to a breakdown of 10% of men and 24%
      of women working part-time. The current workforce is 13% general radiologists and
      87% subspecialists. In 2015, a projected 1,131 to 1,484 jobs will be available
      for radiologists. CONCLUSIONS: Job opportunities for radiologists seem to be
      increasing compared with 2013 and are relatively similar to 2014. Radiologists
      continue to subspecialize in greater numbers, but only 39% of radiologists
      practice more than 50% of the time in their subspecialties.

PMID- 26314794
TI  - Radiologist Hiring Preferences Based on Practice Needs.
AB  - BACKGROUND: The ACR Commission on Human Resources and Commission on General,
      Small and Rural Practice collaborated on developing a question regarding hiring
      preferences to include in the annual Commission on Human Resources Workforce
      Survey in order to understand hiring preferences. METHODS: Group leads were asked
      to rank five types of prospective radiologists from most desirable to least
      desirable for hire on the basis of the needs of their practices: single-specialty
      radiologists, focusing on only one subspecialty; single-specialty radiologists
      with general capabilities; multispecialty radiologists; general radiologists; and
      radiologists who did two fellowships in the same specialty. RESULTS: The most
      desired hiring preference was for a single-specialty radiologist with general
      capabilities. Sixty-eight percent of the practice leaders identified a single
      specialty radiologist with general capabilities as the most desirable type of
      individual to hire, compared with 21% who chose multispecialty radiologists, 13%
      who chose single-specialty radiologists and general radiologists, and 5% who
      expressed a preference for radiologists who did two fellowships in the same
      specialty. CONCLUSIONS: The most desirable candidates for hire appear to be those
      who are fellowship trained as subspecialists but who are also capable of reading
      in other clinical areas or modalities. This preference is true for most private
      practices, multispecialty practices, and hospital-owned practices. In contrast to
      those practices, chairs and leaders of academic medical center practices prefer
      to hire single-specialty radiologists slightly more than single-specialty
      radiologists with general capabilities.

PMID- 26314795
TI  - Lecture Evaluations by Medical Students: Concepts That Correlate With Scores.
AB  - PURPOSE: The didactic lecture remains one of the most popular teaching formats in
      medical education; yet, factors that most influence lecturing success in
      radiology education are unknown. The purpose of this study is to identify
      patterns of narrative student feedback that are associated with relatively higher
      and lower evaluation scores. METHODS: All student evaluations from our core
      radiology elective during 1 year were compiled. All evaluation comments were
      tagged, to identify discrete descriptive concepts. Correlation coefficients were
      calculated, for each tag with mean evaluation scores. Tags that were the most
      strongly associated with the highest- versus lowest-rated (> or < 1 SD) lectures
      were identified. RESULTS: A total of 3,262 comments, on 273 lectures, rated by 77
      senior medical students, were analyzed. The mean lecture score was 8.96 +/- 0.62.
      Three tags were significantly positively correlated with lecture score:
      "interactive"; "fun/engaging"; and "practical/important content" (r = 0.39, r =
      0.34, and r = 0.32, respectively; all P < .001). More tags (n = 12) were
      significantly negatively correlated with score; the three tags with the strongest
      such correlation were: "not interactive"; "poorly structured or unevenly paced";
      and "content too detailed or abundant" (r = -0.44, r = -0.39, and r = -0.36,
      respectively; all P < .001). Analysis of only the highest- and lowest-rated
      lectures yielded similar results. CONCLUSIONS: Several factors were identified
      that were strongly associated with lecture score. Among the actionable
      characteristics, interactive lectures with appropriately targeted content (ie,
      practical/useful) were the most highly rated.

PMID- 26314796
TI  - Analysis of risk factors for poor prognosis in conservatively managed early-stage
      spontaneous osteonecrosis of the knee.
AB  - BACKGROUND: Management guidelines for early-stage spontaneous osteonecrosis of
      the knee (SONK) have not been established. The purposes of this study were to
      review the outcome of conservative treatment for patients with early-stage SONK
      and to examine clinical factors affecting the prognosis. METHODS: Diagnosis of
      early-stage SONK was made based on the criteria consisting of specific clinical
      features including magnetic resonance imaging (MRI) findings. During the study
      period, all patients with this diagnosis underwent standardized conservative
      treatment. The study population comprised 38 knees in 36 patients with a mean age
      at presentation of 66.4years. The mean follow-up period was 34.9months. During
      the treatment course, progressive joint space narrowing or collapse of bony
      contours identified in serial follow-up radiographs was regarded as indicating a
      poor prognosis. The significance of potential prognostic factors such as age,
      gender, obesity, coronal alignment, lesion size, and MRI findings was analyzed
      using a multivariate logistic regression analysis. RESULTS: The prognosis was
      defined to be poor in eight knees (21.1%). The multivariate logistic regression
      analysis for potential risk factors revealed that only varus alignment with a
      femorotibial angle (FTA) of 180 degrees  or more on the initial radiograph was
      significantly associated with the poor prognosis (P=0.01, odds ratio 28.1) while
      no other factors significantly correlated with the prognosis. CONCLUSIONS:
      Approximately 80% of patients with early-stage SONK could be managed successfully
      with conservative treatment without progression of the disease process. The
      presence of varus deformity (FTA of 180 degrees  or more) was significantly
      associated with poor prognosis complicated with progressive deformity and
      prolonged disability. LEVEL OF EVIDENCE: Level IV, case series.

PMID- 26314797
TI  - Plasma MicroRNAs as Novel Biomarkers for Patients with Intraductal Papillary
      Mucinous Neoplasms of the Pancreas.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal cancers
      worldwide, partly because methods are lacking to detect disease at an early,
      operable stage. Noninvasive PDAC precursors called intraductal papillary mucinous
      neoplasms (IPMN) exist, and strategies are needed to aid in their proper
      diagnosis and management. Data support the importance of miRNAs in the
      progression of IPMNs to malignancy, and we hypothesized that miRNAs may be shed
      from IPMN tissues and detected in blood. Our primary goals were to measure the
      abundance of miRNAs in archived preoperative plasma from individuals with
      pathologically confirmed IPMNs and healthy controls and discover plasma miRNAs
      that distinguish between IPMN patients and controls and between "malignant" and
      "benign" IPMNs. Using novel nCounter technology to evaluate 800 miRNAs, we showed
      that a 30-miRNA signature distinguished 42 IPMN cases from 24 controls [area
      underneath the curve (AUC) = 74.4; 95% confidence interval (CI), 62.3-86.5, P =
      0.002]. The signature contained novel miRNAs and miRNAs previously implicated in
      pancreatic carcinogenesis that had 2- to 4-fold higher expression in cases than
      controls. We also generated a 5-miRNA signature that discriminated between 21
      malignant (high-grade dysplasia and invasive carcinoma) and 21 benign (low- and
      moderate-grade dysplasia) IPMNs (AUC = 73.2; 95% CI, 57.6-73.2, P = 0.005), and
      showed that paired plasma and tissue samples from patients with IPMNs can have
      distinct miRNA expression profiles. This study suggests feasibility of using new
      cost-effective technology to develop a miRNA-based blood test to aid in the
      preoperative identification of malignant IPMNs that warrant resection while
      sparing individuals with benign IPMNs the morbidity associated with
      overtreatment.

PMID- 26314799
TI  - Celebrating Soft Matter's 10th Anniversary: Approaches to program the time domain
      of self-assemblies.
AB  - Self-regulating reconfigurable soft matter systems are of great interest for
      creating adaptive and active material properties. Such complex functionalities
      emerge from non-linear and interactive behavior in space and time as demonstrated
      by a plethora of dynamic, self-organizing biological structures (e.g., the
      cytoskeleton). In man-made self-assemblies, patterning of the spatial domain has
      advanced to creating hierarchical structures via precise molecular programming.
      However, orchestration of the time domain of self-assemblies is still in its
      infancy and lacks universal design principles. In this Emerging Area article we
      outline major strategies for programming the time domain of self-assemblies
      following the concepts of regulatory reaction networks, energy dissipation and
      kinetic control. Such concepts operate outside thermodynamic equilibrium and pave
      the way for temporally patterned, dynamic, and autonomously acting functional
      materials. 

PMID- 26314798
TI  - Specificity of V1-V2 orientation networks in the primate visual cortex.
AB  - The computation of texture and shape involves integration of features of various
      orientations. Orientation networks within V1 tend to involve cells which share
      similar orientation selectivity. However, emergent properties in V2 require the
      integration of multiple orientations. We now show that, unlike interactions
      within V1, V1-V2 orientation interactions are much less synchronized and are not
      necessarily orientation dependent. We find V1-V2 orientation networks are of two
      types: a more tightly synchronized, orientation-preserving network and a less
      synchronized orientation-diverse network. We suggest that such diversity of V1-V2
      interactions underlies the spatial and functional integration required for
      computation of higher order contour and shape in V2. 

PMID- 26314800
TI  - Single cell nanobiosensors for dynamic gene expression profiling in native tissue
      microenvironments.
AB  - A gold nanorod-locked nucleic acid nano-biosensor for dynamic single-cell gene
      expression analysis in living cells and tissues is developed. The nanoparticle
      facilitates endocytic delivery and dynamic monitoring of the gene expression in
      human umbilical cord endothelial cells, mouse skin tissues, mouse retina tissues,
      and mouse cornea tissues at the single-cell level. 

PMID- 26314801
TI  - Capturing the interaction types of two Bt toxins Cry1Ac and Cry2Ab on suppressing
      the cotton bollworm by using multi-exponential equations.
AB  - Transgenic crops are increasingly promoted for their practical effects on
      suppressing certain insect pests, but all transgenic crops are not equally
      successful. The insect pests can easily develop resistance against single
      Bacillus thuringiensis (Bt) toxin transgenic crops. Therefore, transgenic crops
      including two or more mixed Bt-toxins can solve this problem by delaying the
      resistance development and killing the majority of targeted pests before the
      evolution of resistance. It is important to test the controlling effects of
      transgenic crops including multiple mixed toxins on a particular insect pest.
      Previous research has checked the cross-resistance and interactions between Bt
      toxins Cry1Ac and Cry2Ab against one susceptible and four resistant strains of
      cotton bollworm. The results showed that independence was the main interaction
      type between two toxins for the susceptible strain, whereas synergism was the
      main interaction type for any one resistant strain. However, the optimal
      combinations of two toxins were not obtained. In the present study, we developed
      two multi-exponential equations (namely bi- and tri-exponential equations) to
      describe the combination effects of two Bt toxins. Importantly, the equations can
      provide predictions of combination effects of different continuous concentrations
      of two toxins. We compared these two multi-exponential equations with the
      generalized linear model (GLM) in describing the combination effects, and found
      that the bi- and tri-exponential equations are better than GLM. Moreover, the bi
      exponential equation can also provide the optimal dose combinations for two
      toxins. 

PMID- 26314802
TI  - Publication patterns in developmental psychology: Trends and social networks.
AB  - Interest in publication patterns has been steady. Journals have instituted
      policies in an effort to curb bias and provide globally representative research.
      This study aimed to examine if publication patterns were present in two
      developmental psychology journals. It also explored the social networks of
      prominent authors and the prevalence of informal author-editor relationships,
      searching for any potential power groups. Data were taken from empirical articles
      published between 2005 and 2014 in Child Development (CD) and The International
      Journal of Early Childhood (IJEC) data points were geographical authorship
      affiliation, informal author relationships as established by co-publishing, and
      connections to journal editors via identical affiliation. Results confirmed the
      previously established North American dominance in published research. In CD a
      strongly interlinked social network was identified between authors over the 10
      years, with 15 chief influentialists binding groups of authors together. Results
      suggest that patterns are still present in published research in the realm of
      developmental psychology. To conclude, the potential implications of these
      patterns within developmental psychology are presented.

PMID- 26314803
TI  - Polymeric nanoparticles: the future of nanomedicine.
AB  - Polymeric nanoparticles (NPs) are one of the most studied organic strategies for
      nanomedicine. Intense interest lies in the potential of polymeric NPs to
      revolutionize modern medicine. To determine the ideal nanosystem for more
      effective and distinctly targeted delivery of therapeutic applications, particle
      size, morphology, material choice, and processing techniques are all research
      areas of interest. Utilizations of polymeric NPs include drug delivery techniques
      such as conjugation and entrapment of drugs, prodrugs, stimuli-responsive
      systems, imaging modalities, and theranostics. Cancer, neurodegenerative
      disorders, and cardiovascular diseases are fields impacted by NP technologies
      that push scientific boundaries to the leading edge of transformative advances
      for nanomedicine.

PMID- 26314805
TI  - Risk of second primary malignancy after nasopharyngeal carcinoma in the United
      States: A population-based study.
AB  - BACKGROUND: The purpose of this study was to evaluate the incidence of second
      primary malignancies in patients diagnosed with an index nasopharyngeal carcinoma
      (NPC) in the United States. METHODS: The cohort was assembled from the
      Surveillance, Epidemiology, and End Results (SEER) database with a primary NPC
      between 1973 and 2005. RESULTS: There was a 47% increased risk of second primary
      malignancy. The sites with increased risk include the oral cavity and pharynx
      (standardized incidence ratio [SIR] = 7.11; 95% confidence interval [CI] = 5.21
      9.49), esophagus (SIR = 3.50; 95% CI = 1.68-6.44), nose, nasal cavity, and middle
      ear (SIR = 15.54; 95% CI = 5.70-33.83), and lung and bronchus (SIR = 2.39; 95% CI
      = 1.91-2.96). CONCLUSION: Patients with NPC are likely at a significant risk for
      second primary malignancies, most notably in the oral cavity and pharynx, which
      is most likely related to genetic susceptibility, increased surveillance, and
      treatment effects. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1130-E1136,
      2016.

PMID- 26314804
TI  - Identification of the interaction of VP1 with GM130 which may implicate in the
      pathogenesis of CVB3-induced acute pancreatitis.
AB  - Coxsackievirus B3 (CVB3) is a causative agent of viral myocarditis, pancreatitis,
      and meningitis in humans. Although the susceptibility of CVB3-induced acute
      pancreatitis is age-dependent, the underlying mechanisms remain unclear. Here we
      identified the host factor Golgi matrix protein 130 (GM130) as a novel target of
      CVB3 during CVB3-induced acute pancreatitis. The viral protein VP1 interacted
      with GM130, disrupted GM130-GRASP65 complexes, and caused GM130 degradation,
      which may lead to disruption of the Golgi ribbon and development of acute
      pancreatitis in mice. Interestingly, the expression level of GM130 in mouse
      pancreas was age-dependent, which was nicely correlated with the age-associated
      susceptibility of CVB3-induced acute pancreatitis. Furthermore, interference RNA
      mediated knockdown of GM130 significantly reduced CVB3 replication in HeLa cells.
      Taken together, the study identified GM130 as a novel target of CVB3, which may
      implicate in the pathogenesis of CVB3-induced acute pancreatitis. 

PMID- 26314806
TI  - Disease-free survival following high dose or standard dose therapy in patients
      with amyloidosis.

PMID- 26314807
TI  - Defining the Burden of Osteoarthritis in Population-Based Surveys.

PMID- 26314808
TI  - The prevalence of sensitization to inhalant allergens in children with atopic
      dermatitis.
AB  - BACKGROUND: The role of sensitization to inhalant allergens in atopic dermatitis
      (AD) in children is uncertain. The aim of our study was to assess the
      relationship of AD symptoms with sensitization to aeroallergens in Polish
      children ages 6-7 and 13-14 years. MATERIAL AND METHOD: Epidemiology of Allergic
      Disorders in Poland is a randomized study with medical examination according to
      the ECRHS II and the International Study of Asthma and Allergies in Childhood
      standards in nine selected regions of Poland. We studied 6-7-year-old (n = 4510)
      and 13-14-year-old children (n = 4721). A total of 1583 children (25%) had a
      medical examination and a skin-prick test (SPT) with the 15 most common
      aeroallergens. RESULTS: AD was diagnosed in 235 children (8.9%) (8.7%, 6-7-year
      old children; 9.0%, 13-14-year-old children; 8.6% boys and 9.1% girls). AD was
      more frequent in urban versus rural habitants (9.6% versus 3.7%; p < 0.05) and in
      participants with a positive atopy history versus those without atopy (9.4%
      versus 5.1%; p < 0.05). Positive SPT was found in 1165 children (43.9%) (38.5%
      boys, 49.5% girls) and 64.72% with AD versus 41.9% without AD (p < 0.05) and more
      common in the rural region versus urban setting among 6-7 year-olds (71.8% versus
      35.0%; p < 0.05). The most frequent allergic reaction was Dermatophagoides
      pteronyssinus (13.5%), Dermatophagoides farina (11.7%), and grasses/crop plants
      (11.8%). The same pattern was seen in participants with and those without AD.
      Children with AD had more frequent positive SPT for all aeroallergens (p < 0.05).
      CONCLUSION: AD should be more frequent in children with a positive atopy history
      and in children who live in the city. Aeroallergens play an essential role in
      pathogenesis of eczema in children. House-dust mites and grass pollen proved to
      be the most common relevant aeroallergens.

PMID- 26314809
TI  - The talking card: Randomized controlled trial of a novel audio-recording tool for
      asthma control.
AB  - BACKGROUND: Asthma care plans typically include complicated written instructions.
      Customized, audio-recorded instructions may bridge health literacy gaps and
      improve treatment plan understanding. OBJECTIVE: To measure the effects of a
      recordable greeting card-style tool (Talking Card) on asthma control and parental
      care of children with asthma. METHODS: Multisite randomized trial in two primary
      care clinics, including children 4-11 years old with uncontrolled asthma and
      their parents. Parent-child dyads were randomized to usual care of asthma or
      usual care plus the Talking Card. Dyads completed three asthma-focused visits
      over 3 months. At the visit, card recipients received customized instructions
      recorded by the pediatrician onto an audio chip in the card. Asthma control was
      measured by using the Childhood Asthma Control Test. Card use and parental
      satisfaction were measured by parental survey (card arm only). Outcomes were
      analyzed by using generalized estimating equations and frequency distributions.
      RESULTS: Sixty-four dyads participated and attended 166 clinic visits. Card use
      was associated with a 1.6-point increase in Childhood Asthma Control Test score
      (p = 0.02) and a clinic visit regardless of card use with a three-point increase
      (p < 0.001). Satisfaction and self-efficacy were high among the card users. The
      mean satisfaction score was 8.9 of 10, with 96% agreeing or strongly agreeing
      that the card helped them take better care of asthma. CONCLUSIONS: The Talking
      Card, a novel audio communication tool, was associated with improved asthma
      control and deemed highly desirable by parents and children struggling to control
      asthma. This inexpensive portable tool may be useful in other chronic disorders
      and in locales with low literacy and poor access to digital technology.

PMID- 26314810
TI  - Association of inflammatory bowel disease with asthma risk: A nationwide cohort
      study.
AB  - OBJECTIVE: We evaluated the risk of asthma development in adult patients with
      inflammatory bowel disease (IBD) in a nationwide population. METHODS: A
      retrospective cohort study was conducted by using data retrieved from the Taiwan
      National Health Insurance Research Database. Patients, ages 20 year or older,
      with newly diagnosed IBD between 2000 and 2005 were identified and randomly
      frequency-matched (based on sex, age, and index year) with four times the number
      of enrollees without IBD from the general population. Both cohorts were followed
      up until the end of 2011 to examine the incidence of asthma. Cox proportional
      hazard regression analysis was used to measure the hazard ratios (HR) of asthma
      in the IBD cohort compared with that in the non-IBD cohort. RESULTS: The IBD and
      non-IBD cohorts comprised 5260 patients with IBD and 21,040 participants,
      respectively. After adjustment for covariates, the IBD cohort exhibited a 1.50
      fold increased risk for asthma (HR 1.50, [95% confidence interval {CI}, 1.32
      1.71]). Further analysis according to the two major forms of IBD revealed that
      the adjusted HR of asthma was 1.46 (95% CI, 1.03-2.07) and 1.50 (95% CI, 1.31
      1.72) in patients with ulcerative colitis and Crohn's disease, respectively,
      compared with the non-IBD cohort. CONCLUSION: After adjustment for comorbidities,
      patients with IBD were associated with a higher subsequent risk of asthma.

PMID- 26314811
TI  - Association of rheumatoid arthritis with allergic diseases: A nationwide
      population-based cohort study.
AB  - BACKGROUND: Low-grade inflammation conditions, e.g., type 2 diabetes, have been
      shown to be associated with an increased risk of rheumatoid arthritis (RA).
      However, the association between other chronic inflammatory conditions, e.g.,
      asthma, allergic rhinitis, and atopic dermatitis, is still unclear. OBJECTIVE: To
      investigate the risk of RA in patients with allergic diseases, including asthma,
      allergic rhinitis, and atopic dermatitis, by using a nationwide health claims
      database. METHODS: The Taiwan National Health Insurance Research Database was
      used to assemble a cohort of 170,570 patients ages 20 years old and older
      diagnosed with allergic diseases, including asthma, allergic rhinitis, or atopic
      dermatitis. A comparison cohort of 170,238 patients was constructed from the same
      data base, with frequency matching for sex, 10-year age group, and year of
      insurance enrollment. Cox proportional hazards regression analyses were conducted
      to assess the association between the allergic diseases and incident RA. RESULTS:
      Asthma (adjusted hazard ratio [AHR] 1.67, [95% confidence interval {CI}], 1.32
      2.62) and allergic rhinitis (AHR 1.62 [95% CI, 1.33-1.98]) were significantly
      associated with the incident RA. These associations remained significant even
      after excluding patients who had concurrent diagnoses of asthma and allergic
      rhinitis. Patients with more than one allergic disease had an increased risk of
      developing RA (AHR 1.98 [95% CI, 1.50-2.62]). Subgroup analysis further indicated
      that middle-aged and elderly female patients with more than one allergic disease
      exhibited a high risk of developing RA. CONCLUSION: Significant associations
      between common allergic diseases and incident RA was found in this population
      based cohort study. Our findings provided support to the hypothesis that allergic
      diseases and RA might share a similar underlying etiologic pathway related to
      chronic inflammatory responses.

PMID- 26314812
TI  - Letter to the Editor: Incorrect conclusions regarding deposition of conventional
      mometasone furoate (MF) nasal spray.

PMID- 26314813
TI  - Children at risk: Conditions which can increase the occurrence of allergic
      disease.

PMID- 26314814
TI  - Update on the utility of corticosteroids in acute pediatric respiratory
      disorders.
AB  - BACKGROUND: Corticosteroids, delivered systemically and by inhalation, are widely
      used for the treatment of multiple acute respiratory illnesses in children.
      However, the level of evidence to support the utility of this therapy varies
      between these different acute respiratory illnesses. OBJECTIVE: To summarize the
      evidence regarding the utility of corticosteroids in the management of common
      acute pediatric respiratory conditions and to highlights the controversies
      regarding their use. METHODS: Literature search of manuscripts describing the
      evidence regarding the efficacy of corticosteroids (systemic and inhaled) in the
      management of: acute asthma exacerbation among school age children, acute
      episodic wheeze among preschool children, viral croup, and acute viral
      bronchiolitis. RESULTS: Current evidence indicates that systemic corticosteroids
      provide benefits for the treatment of acute asthma exacerbations in school age
      children, mainly in the acute care setting. In addition, high dose inhaled
      corticosteroid therapy administered in the Emergency Department appears to have
      comparable effect for the prevention of asthma-related hospital admission as
      systemic corticosteroids in this age group. In contrast, most available studies
      have not shown benefit for systemic corticosteroids during acute wheezing
      episodes in preschool children. Systemic corticosteroids decrease symptoms and
      the rate of hospital admissions in patients with severe croup; however,
      corticosteroids have no role in the treatment of acute bronchiolitis and their
      use in this condition should be discouraged. CONCLUSION: Corticosteroids
      treatment response varies between the acute respiratory illnesses presented in
      this review. Future research should aim to fill the current gaps-of-knowledge
      regarding the utility this intervention such as the identification of specific
      wheezing phenotypes among preschool children which might benefit from systemic
      corticosteroids as a treatment for acute viral wheeze.

PMID- 26314815
TI  - Chronic rhinosinusitis management beyond intranasal steroids and saline solution
      irrigations.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) is a heterogeneous disease with clinical
      manifestations that are influenced by the presence or absence of nasal polyposis.
      Understanding of the current and future treatment modalities for CRS is essential
      in preventing exacerbation and morbidity associated with this chronic condition.
      OBJECTIVE: The aim of this article is to review the evidence behind current
      medical therapies and potential new treatments for CRS. METHODS: Scientific
      literature regarding intranasal and systemic antibiotics, intranasal systemic
      corticosteroids, and monoclonal antibodies as interventions for CRS with and
      without nasal polyps was reviewed. RESULTS: The literature supports the use of
      topical or systemic glucocorticoids in patients with nasal polyps, and there
      appears to be a role for systemic antibiotics in the treatment of acute
      exacerbations of CRS with nasal polyps. The response to corticosteroids or
      antibiotics in the treatment of exacerbations of CRS without nasal polyps is
      variable. Due to the lack of appropriately designed trials, there is weak
      evidence for the adjunctive use of immunotherapy at this time. Monoclonal
      antibodies that target Immunoglobulin E and T helper cell 2 cytokines have been
      clinically effective in symptom reduction for some patients with CRS with nasal
      polyps although further studies are needed. CONCLUSION: Current therapies used in
      the treatment of CRS are discussed.

PMID- 26314816
TI  - Mode of delivery and risk for development of atopic diseases in children.
AB  - Atopic diseases are a major public health problem worldwide, and several factors
      are thought to contribute to this rapid increase. The observed association
      between mode of delivery and risk of atopy in childhood has had a great deal of
      interest during the past few decades. In fact, even during delivery, exposure to
      antigens can index immune system in newborn, which induces the release of
      biologically active molecules, which are polarizing immune responses toward the T
      helper 2 atopic profile. However, to date, studies on the relationship between
      mode of delivery and atopy have produced conflicting findings. The aim of this
      review was to summarize what is known about the relationship between mode of
      delivery and risk of atopic diseases in children. A literature search of
      electronic databases was undertaken for the major studies published from 1994 to
      today. The databases searched were PubMed, EMBASE, Medline, and Cochrane Library.
      The following key words were used: mode of delivery, cesarean section, vaginal
      delivery, atopy, and atopic diseases. 

PMID- 26314817
TI  - Pharmacokinetics of fluticasone propionate multidose, inhalation-driven, novel,
      dry powder inhaler versus a prevailing dry powder inhaler and a metered-dose
      inhaler.
AB  - BACKGROUND: A novel inhalation-driven multidose dry powder inhaler (MDPI) that
      eliminates the need for the patient to coordinate device actuation with
      inhalation has been developed for delivery of inhaled asthma medications.
      OBJECTIVE: To characterize the pharmacokinetics of single-dose fluticasone
      propionate (Fp) MDPI compared with single doses of Fp dry powder inhaler (DPI)
      and a metered-dose inhaler (MDI) in healthy subjects. METHODS: This was a single
      center, open-label, randomized, three-period crossover, single-dose pilot study
      in healthy adults ages 18 to 45 years. Eligible subjects (N = 18) were randomized
      to one of six treatment sequences that contained three treatment arms: Fp MDPI
      400 MUg/inhalation * two inhalations (800 MUg total dose); Fp DPI 250
      MUg/inhalation * four (1000 MUg total dose); and Fp MDI 220 MUg/inhalation * four
      (880 MUg total dose). Pharmacokinetics (area under concentration-versus-time
      curve [AUC], maximum plasma concentration [Cmax], time to Cmax [tmax], and
      elimination half-life [t1/2]), safety, and tolerability were assessed for each
      treatment. RESULTS: Plasma Fp concentration-versus-time curves were comparable
      across treatments. Geometric mean AUC0-t and Cmax for Fp MDPI 800 MUg were 19%
      and 18% higher, respectively, compared with Fp DPI 1000 MUg, and 47% and 82%
      higher, respectively, compared with Fp MDI 880 MUg. Median tmax (60.0-60.6
      minutes) and median t1/2 (9.1-9.8 hours) were comparable across the three
      treatments. Single-dose Fp was well tolerated, with no new safety issues noted.
      CONCLUSION: Single-dose administration of Fp MDPI 800 MUg produced systemic
      exposure comparable with those for Fp DPI 1000 MUg and Fp MDI 880 MUg.

PMID- 26314819
TI  - Differential skin test reactivity to pollens in pollen food allergy syndrome
      versus allergic rhinitis.
AB  - BACKGROUND: Pollen food allergy syndrome (PFAS), also called oral allergy
      syndrome, is a form of food allergy in which uncooked foods cause allergic
      symptoms generally limited to the oral mucosa. It occurs in a subset of patients
      with pollen allergy, although not all patients have prominent rhinitis symptoms.
      PFAS is related to antigenic similarity between the pollen and food allergen.
      OBJECTIVE: The size of skin test reactions in a group of subjects with pollen
      sensitivity with PFAS was compared with a group of subjects who were pollen
      sensitive and without PFAS. Self-reported rhinitis symptoms between the two
      groups were compared to identify if symptom severity differed. METHODS: Twenty
      subjects with PFAS and 20 subjects with seasonal allergic rhinitis without PFAS
      were enrolled in the study. All the subjects underwent standard skin-prick
      testing to a panel of common allergens, including select fresh fruits and
      vegetables. The subjects completed a Mini Rhinoconjunctivitis Quality of Life
      Questionnaire as part of their clinical evaluation. The subjects with PFAS and
      those without PFAS were compared statistically. RESULTS: The subjects with PFAS
      had significantly larger-sized skin-prick test results specific to pollens (p <
      0.05). Despite the larger-sized skin-prick test results, the subjects with
      allergic rhinitis and PFAS reported milder nasal symptoms in relation to pollen
      skin test result size when compared with allergic rhinitis controls without PFAS.
      CONCLUSIONS: Our study outlined basic differences between two seemingly similar
      patient groups with a particularly striking discordance between skin test result
      sizes and rhinitis symptoms. This discordance should be explored further to
      increase mechanistic understanding of allergen cross-reactivity in PFAS.

PMID- 26314818
TI  - Risk of herpes zoster in children with asthma.
AB  - BACKGROUND: There is literature that indicates the association of asthma with an
      increased risk of common and serious microbial infections. We recently reported
      an increased risk of vaccine-preventable diseases, e.g., herpes zoster (HZ) among
      children with asthma, defined by predetermined asthma criteria. Little is known
      about whether this association is persistent if the asthma status is defined by
      different asthma criteria, e.g., the Asthma Predictive Index, given the
      heterogeneity of asthma. OBJECTIVE: To assess the consistency of the association
      between asthma and the risk of HZ in children. METHODS: This is a population
      based case-control study based on all pediatric patients with HZ between 1996 and
      2001 in Olmsted County, Minnesota, and 1:1 age- and sex-matched controls without
      a history of HZ who were enrolled in our previous study. The original Asthma
      Predictive Index criteria was operationalized by two or more wheezing episodes in
      a year for the first 3 years of life plus one of the major (physician-diagnosed
      asthma for a parent or physician-diagnosed eczema for a patient) or two of the
      minor criteria (physician-diagnosed allergic rhinitis for a patient, wheezing
      apart from cold, or eosinophilia [>=4%]). Data were fit to traditional logistic
      regression models to calculate odds ratios and 95% confident intervals. RESULTS:
      Of the original cohort (n = 554), 95 (17%) did not meet the enrollment criteria
      for this study, which left 459. Of the 221 patients, 53% were female, with a mean
      (standard deviation) age of 9.7 +/- 4.2 years. The risk of HZ was increased in
      children with asthma defined by the API controlling for a varicella vaccine
      history and atopic status (adjusted odds ratio 2.56 [95% confidence interval,
      1.08-6.56]). CONCLUSIONS: The association between asthma and increased risk of HZ
      in children and adolescents is consistent, independent of asthma definitions.
      Asthma might be an important clinical condition to be considered in HZ vaccine
      studies.

PMID- 26314820
TI  - Nonsteroidal anti-inflammatory drug hypersensitivity among children.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAID) are the second-most
      frequent drugs that cause hypersensitivity reactions among children. Studies
      related to NSAIDs hypersensitivity in children are limited. In this study, we
      aimed to evaluate children admitted with suspicion of NSAIDs reaction. METHOD:
      Between January 1, 2011, and November 30, 2014, we included patients with
      suspicion of NSAIDs hypersensitivity in our clinic. For evaluation, skin tests
      and oral provocation tests with the drug (suspected or alternative) were
      proposed. Reactions were classified and defined according to the latest European
      Academy of Allergy and Clinical Immunology position paper on NSAID
      hypersensitivity. RESULTS: During the study period, 123 patients (with 136 drug
      reactions) were admitted to our clinic with suspected NSAID hypersensitivity. The
      mean (standard deviation) age of the patients, 67 female (55%), was 83.10 +/-
      56.05 months. Thirteen patients described reactions to more than one chemically
      unrelated NSAID, and 110 patients described reactions with chemically similar
      drugs. Eight patients were not included because they did not have provocation
      tests. Thus, 115 patients were evaluated. A hundred and thirty provocations were
      performed. Twenty patients (17.4%) were diagnosed with NSAID hypersensitivity (13
      patients diagnosed by provocation tests and 7 patients diagnosed according to
      their history). The most frequently encountered agent was ibuprofen (50%
      [10/20]). Eighty percent (16 patients) of the reactions were considered "non
      cross-reactive type." Fifteen patients (75%) were classified as having single
      NSAID-induced urticaria and/or angioedema, three patients were classified as
      having NSAID-induced urticaria and/or angioedema, one patient was classified as
      having NSAID-exacerbated respiratory disease, and the other patients were
      classified as having single-NSAID-induced delayed hypersensitivity reactions.
      CONCLUSION: Detailed history and drug provocation tests are important to verify
      NSAID hypersensitivity. The most common type is the non-cross-reactive type, and,
      in our study, the most common responsible drug was ibuprofen.

PMID- 26314821
TI  - The minimal important difference for measures of urticaria disease activity:
      Updated findings.
AB  - BACKGROUND: The Urticaria Patient Daily Diary (UPDD) is a validated patient
      reported outcome that captures key measures of urticaria disease activity.
      OBJECTIVE: To update estimates of the minimal important difference (MID) for
      urticaria disease activity measures in the UPDD, including the weekly itch
      severity score, weekly number of hives score, weekly average size of largest hive
      score, and the composite measure of itch severity and number of hives over 7
      days, or urticaria activity score 7 (UAS7). METHODS: A total of 975 subjects with
      chronic idiopathic urticaria from three randomized, double-blind, placebo
      controlled studies completed the UPDD and other patient-reported outcome
      assessments (the Dermatology Life Quality Index, Medical Outcomes Study Sleep
      Scale, the Chronic Urticaria Quality-of-Life Questionnaire, the EuroQoL-5
      Dimension Questionnaire) multiple times. MIDs were estimated through a
      combination of distribution- and anchor-based methods. RESULTS: MID estimates
      ranged from 4.5 to 5.0 for the weekly itch severity score, 5.0 to 5.5 for weekly
      hives count score, 9.5 to 10.5 for the UAS7, and 4.0 to 4.5 for the weekly size
      of the largest hive score. CONCLUSION: This analysis provided confirmation of the
      previous MID estimates for the urticaria disease activity measures in the UPDD.

PMID- 26314822
TI  - Analysis of characteristics associated with reinjection of icatibant: Results
      from the icatibant outcome survey.
AB  - PURPOSE: Phase 3 icatibant trials showed that most hereditary angioedema (HAE)
      (C1 inhibitor deficiency) acute attacks were treated successfully with one
      injection of icatibant, a selective bradykinin B2 receptor antagonist. We
      conducted a post hoc analysis of icatibant reinjection for HAE type I and II
      attacks in a real-world setting by using data from the Icatibant Outcome Survey,
      an ongoing observational study that monitors the safety and effectiveness of
      icatibant treatment. METHODS: Descriptive retrospective analyses of icatibant
      reinjection were performed on Icatibant Outcome Survey data (February 2008 to
      December 2012). New attacks were defined as the onset of new symptoms after full
      resolution of the previous attack. Potential associations between the patient and
      attack characteristics and reinjection were explored by using logistic regression
      analysis. RESULTS: Icatibant was administered for 652 attacks in 170 patients
      with HAE type I or II. Most attacks (89.1%) were treated with a single icatibant
      injection. For attacks that required two or three injections, the second
      injection was given a median of 11.0 hours after the first injection, with 90.4%
      of second injections administered >=6 hours after the first injection. Time to
      resolution and attack duration were significantly longer for two or three
      injections versus one icatibant injection (p < 0.0001 and p < 0.05,
      respectively). Multivariate logistic regression analysis identified sex, attack
      severity, and laryngeal attacks as significantly correlated with reinjection (all
      p <= 0.05). These factors did not remain predictors for reinjection when two
      outlier patients with distinct patterns of icatibant use were excluded.
      CONCLUSIONS: In this real-world setting, most HAE attacks resolved with one
      icatibant injection. There was no distinct profile for patients or attacks that
      required reinjection when outliers with substantially different patterns of use
      were excluded. Because new attacks were not distinguished from the recurrence of
      symptoms, reinjection rates may be slightly higher than shown here. Clinical
      trial identifier: NCT01034969.

PMID- 26314823
TI  - A 15-year-old boy with severe combined immunodeficiency, fungal infection, and
      weight gain.
AB  - Hematopoietic stem cell transplantation (HSCT) outcomes in X-linked severe
      combined immune deficiency are most effective when performed with patients <3
      months of age and without coexisting morbidity, and with donor cells from a
      matched sibling. Even under such favorable circumstances, outcomes can be
      suboptimal, and full cellular engraftment may not be complete, which results in
      poor B or natural killer cell function. Protein losing enteropathies can
      accompany persistent immune deficiency disorders with resultant low serum
      globulins (immunoglobulin A [IgA], IgG, IgM) and lymphopenia. Patients with
      immune disorders acquire infections that can be predicted by their immune
      dysfunction. Fungal infections are typically noted in neutropenic (congenital or
      acquired) and T-cell deficient individuals. Coexisting fungal infections are
      rare, even in hosts who are immunocompromised, and they require careful
      evaluation. Antifungal treatment may result in drug-drug interactions with
      significant complications. 

PMID- 26314824
TI  - For the Patient.

PMID- 26314825
TI  - Placental Protein 13 Administration to Pregnant Rats Lowers Blood Pressure and
      Augments Fetal Growth and Venous Remodeling.
AB  - Reduced first-trimester concentrations of placental protein 13 (PP13) are
      associated with subsequent development of preeclampsia, a major pregnancy
      disorder. We previously showed that PP13 has a vasodilatory effect, reduces blood
      pressure and augments expansive remodeling of the uteroplacental vasculature in
      pregnant rats. In this study, slow-release osmotic pumps were implanted in gravid
      rats (on day 8) to provide 1 week of PP13 supplementation. Treatment was
      associated with a reversible blood pressure reduction that returned to normal on
      day 15. In addition, PP13 caused venous expansion that is larger in the venous
      branches closer to the placenta. Then, it increased placental and pup weights.
      Similar administration of a truncated PP13 variant (DelT221) that is unable to
      bind carbohydrates (a rare spontaneous mutation associated with a high frequency
      of severe early preeclampsia among Blacks in South Africa) produced a hypotensive
      effect similar to the full-length molecule, but without venous remodeling and
      increased placental and pup weights. These results indicate the importance of
      PP13 carbohydrate binding for inducing vascular remodeling and improving
      reproductive outcome. Future studies are needed to determine whether beneficial
      effects would be evident in animal models of preeclampsia or in women predisposed
      to the development of preeclampsia. 

PMID- 26314826
TI  - The Search for New Agonists to P2X7R for Clinical Use: Tuberculosis as a Possible
      Target.
AB  - Treatment for tuberculosis is effective with the use of proper antibiotics, but
      the number of drug-resistant cases is increasing. Drug resistance occurred in
      650,000 cases of the 20 million patients in treatment worldwide in 2011, which
      demonstrates the necessity of finding new therapeutic approaches. In this
      context, the search for new medicines and immunomodulators could help reduce the
      prevalence and incidence of multi-drug-resistant tuberculosis cases. Thus several
      preclinical studies demonstrate the involvement of the P2X7 receptor (P2X7R) in
      the control of Mycobacterium tuberculosis (MTB) infection. Adenosine triphosphate
      (ATP), a natural agonist for P2X7R, promotes MTB death and the induction of
      apoptosis in monocytes and macrophages infected with MTB via activation of P2X7R
      by extracellular ATP. In addition, P2X7R activation in the presence of ATP
      increases the expression of major histocompatibility complex (MHC) class II by
      macrophages infected with Mycobacterium bovis (BCG) or MTB, which contributes to
      the generation of the antimicrobial immune response via T cells. Nevertheless,
      one idea that seems overlooked by the "purinergic community" is the use of the
      high-conductance channel associated with P2X7R to increase the passage of
      hydrophilic drugs to the cytoplasm of cells that express the P2X7 pore, a
      potential method for a drug delivery system. In this work, we propose the use of
      P2X7 agonists in conjunction with low molecular weight anti-tuberculosis
      medicines for the treatment of multi-drug-resistant tuberculosis. 

PMID- 26314827
TI  - The Art of Trial Design.

PMID- 26314828
TI  - MicroRNA-200 promotes lung cancer cell growth through FOG2-independent AKT
      activation.
AB  - MicroRNA-200 (miR-200) has emerged as a regulator of the PI3K/AKT pathway and
      cancer cell growth. It was reported that miR-200 can activate PI3K/AKT by
      targeting FOG2 (friend of GATA 2), which directly binds to the p85alpha
      regulatory subunit of PI3K. We found that miR-200 was elevated in early stage
      lung adenocarcinomas when compared with normal lung tissues, and the expression
      of miR-200 promoted the tumor spheroid growth of lung adenocarcinoma cells. We
      show that AKT activation was essential for such oncogenic action of miR-200.
      However, depletion of FOG2 had little effect on AKT activation. By performing a
      reverse-phase protein array, we found that miR-200 not only activated AKT but
      also concomitantly inactivated S6K and increased IRS-1, an S6K substrate that is
      increased on S6K inactivation. Depletion of IRS-1 partially inhibited the miR-200
      dependent AKT activation. Taken together, our results suggest that miR-200 may
      activate AKT in lung adenocarcinoma cells through a FOG2-independent mechanism
      involving IRS-1. Our findings also provide evidence that increased miR-200
      expression may contribute to early lung tumorigenesis and that AKT inhibitors may
      be useful for the treatment of miR-200-dependent tumor cell growth.

PMID- 26314829
TI  - Ethnic differences in cross-sectional associations between impaired glucose
      regulation, identified by oral glucose tolerance test or HbA1c values, and
      cardiovascular disease in a cohort of European and South Asian origin.
AB  - AIMS: We contrasted impaired glucose regulation (prediabetes) prevalence, defined
      according to oral glucose tolerance test or HbA1c values, and studied cross
      sectional associations between prediabetes and subclinical/clinical
      cardiovascular disease (CVD) in a cohort of European and South Asian origin.
      METHODS: For 682 European and 520 South Asian men and women, aged 58-85 years,
      glycaemic status was determined by oral glucose tolerance test or HbA1c
      thresholds. Questionnaires, record review, coronary artery calcification scores
      and cerebral magnetic resonance imaging established clinical plus subclinical
      coronary heart and cerebrovascular disease. RESULTS: Prediabetes was more
      prevalent in South Asian participants when defined by HbA1c rather than by oral
      glucose tolerance test criteria. Accounting for age, sex, smoking, systolic blood
      pressure, triglycerides and waist-hip ratio, prediabetes was associated with
      coronary heart disease and cerebrovascular disease in European participants, most
      obviously when defined by HbA1c rather than by oral glucose tolerance test [odds
      ratios for HbA1c -defined prediabetes 1.60 (95% CI 1.07, 2.39) for coronary heart
      disease and 1.57 (95% CI 1.00, 2.51) for cerebrovascular disease]. By contrast,
      non-significant associations were present between oral glucose tolerance test
      defined prediabetes only and coronary heart disease [odds ratio 1.41 (95% CI
      0.84, 2.36)] and HbA1c -defined prediabetes only and cerebrovascular disease
      [odds ratio 1.39 (95% CI 0.69, 2.78)] in South Asian participants. Prediabetes
      defined by HbA1c or oral glucose tolerance test criteria was associated with
      cardiovascular disease (defined as coronary heart and/or cerebrovascular disease)
      in Europeans [odds ratio 1.95 (95% CI 1.31, 2.91) for HbA1c prediabetes criteria]
      but not in South Asian participants [odds ratio 1.00 (95% CI 0.62, 2.66);
      ethnicity interaction P = 0.04]. CONCLUSIONS: Prediabetes appeared to be less
      associated with cardiovascular disease in the South Asian than in the European
      group. These findings have implications for screening, and early cardiovascular
      prevention strategies in South Asian populations.

PMID- 26314830
TI  - Structured nucleosome fingerprints enable high-resolution mapping of chromatin
      architecture within regulatory regions.
AB  - Transcription factors canonically bind nucleosome-free DNA, making the
      positioning of nucleosomes within regulatory regions crucial to the regulation of
      gene expression. Using the assay of transposase accessible chromatin (ATAC-seq),
      we observe a highly structured pattern of DNA fragment lengths and positions
      around nucleosomes in Saccharomyces cerevisiae, and use this distinctive two
      dimensional nucleosomal "fingerprint" as the basis for a new nucleosome
      positioning algorithm called NucleoATAC. We show that NucleoATAC can identify the
      rotational and translational positions of nucleosomes with up to base-pair
      resolution and provide quantitative measures of nucleosome occupancy in S.
      cerevisiae, Schizosaccharomyces pombe, and human cells. We demonstrate the
      application of NucleoATAC to a number of outstanding problems in chromatin
      biology, including analysis of sequence features underlying nucleosome
      positioning, promoter chromatin architecture across species, identification of
      transient changes in nucleosome occupancy and positioning during a dynamic
      cellular response, and integrated analysis of nucleosome occupancy and
      transcription factor binding. 

PMID- 26314831
TI  - Selective Loss of Signaling Lymphocytic Activation Molecule Family Member 4
      Positive CD8+ T Cells Contributes to the Decreased Cytotoxic Cell Activity in
      Systemic Lupus Erythematosus.
AB  - OBJECTIVE: Engagement of signaling lymphocytic activation molecule family member
      4 (SLAMF4; CD244, 2B4) by its ligand SLAMF2 (CD48) modulates the function and
      expansion of both natural killer cells and a subset of cytotoxic CD8+ T cells.
      Because the cytotoxicity of CD8+ T lymphocytes isolated from patients with
      systemic lupus erythematosus (SLE) is known to be impaired, the aim of this study
      was to assess whether the expression and function of the checkpoint regulator
      SLAMF4 are altered on CD8+ T cells from patients with SLE. METHODS: The
      expression of SLAMF4 by T cells from healthy donors and patients with SLE was
      determined by quantitative polymerase chain reaction and flow cytometry. T cells
      were activated with anti-CD3 antibody, and degranulation activity was monitored
      by the surface expression of lysosome-associated membrane protein 1 (LAMP-1;
      CD107a). The SLAMF4+ and SLAMF4- CD8+ T cell subpopulations were characterized by
      LAMP-1, perforin, and granzyme B expression and viral peptide-induced
      proliferation. RESULTS: SLAMF4 gene and surface protein expression was down
      regulated in CD8+ T cells from SLE patients compared with that in cells obtained
      from healthy donors. Importantly, SLE patients had significantly fewer SLAMF4+
      CD8+ T cells compared with healthy donors. SLAMF4- CD8+ T cells from SLE patients
      had a decreased cytotoxic capacity and decreased proliferative responses to viral
      peptides. The loss of memory SLAMF4+ CD8+ T cells in SLE patients was linked to
      the fact that these cells have an increased propensity to lose CD8 expression and
      become double-negative T cells. CONCLUSION: A selective loss of SLAMF4+ CD8+ T
      cells contributes to the compromised ability of T cells from patients with SLE to
      fight infection.

PMID- 26314832
TI  - Decreased Core Crystallinity Facilitated Drug Loading in Polymeric Micelles
      without Affecting Their Biological Performances.
AB  - Cargo-loading capacity of polymeric micelles could be improved by reducing the
      core crystallinity and the improvement in the amount of loaded cargo was cargo
      polymer affinity dependent. The effect of medium chain triglyceride (MCT) in
      inhibiting PCL crystallization was confirmed by DSC and polarized microscope.
      When incorporating MCT into polymeric micelles, the maximum drug loading of
      disulfiram (DSF), cabazitaxel (CTX), and TM-2 (a taxane derivative) increased
      from 2.61 +/- 0.100%, 13.5 +/- 0.316%, and 20.9 +/- 1.57% to 8.34 +/- 0.197%,
      21.7 +/- 0.951%, and 28.0 +/- 1.47%, respectively. Moreover, the prepared oil
      containing micelles (OCMs) showed well-controlled particle size, good stability,
      and decreased drug release rate. MCT incorporation showed little influence on the
      performances of micelles in cell studies or pharmacokinetics. These results
      indicated that MCT incorporation could be a core construction module applied in
      the delivery of hydrophobic drugs. 

PMID- 26314834
TI  - Afatinib: a second-generation EGF receptor and ErbB tyrosine kinase inhibitor for
      the treatment of advanced non-small-cell lung cancer.
AB  - First-generation reversible EGF receptor (EGFR) tyrosine kinase inhibitors (TKIs)
      changed our understanding of advanced non-small-cell lung cancer biology and
      behavior. The presence of sensitizing EGFR mutations in advanced non-small-cell
      lung cancer defines a subset of patients with a better prognosis and sensitivity
      to EGFR-TKIs with a better response rate, progression-free survival, quality of
      life and symptom control than with chemotherapy in the first-line therapy
      setting. However, current EGFR-TKIs show minimal responses in EGFR wild-type
      patients or with acquired TKI resistance mediated through the EGFR T790M allele.
      Afatinib is an irreversible pan-ErbB-TKI, active against wild-type EGFR,
      sensitizing and T970M-mutant EGFR, ErbB2 and ErbB4 receptors, and represents a
      step change between reversible first-generation and future irreversible highly
      specific third-generation EGFR-TKIs. Here, we review the clinical development of
      afatinib through the LUX-Lung trials portfolio highlighting benefits and
      toxicities. 

PMID- 26314833
TI  - Effects of APOE promoter polymorphism on the topological organization of brain
      structural connectome in nondemented elderly.
AB  - The polymorphism of the Apolipoprotein E (APOE) promoter rs405509 can regulate
      the transcriptional activity of the APOE gene and is related to Alzheimer's
      disease (AD). However, its effects on cognitive performance and the underlying
      brain mechanisms remain unknown. Here, we performed a battery of
      neuropsychological tests in a large sample (837 subjects) of nondemented elderly
      Chinese people, and explored the related brain mechanisms via the construction of
      diffusion MRI-based structural connectome and graph analysis from a subset (84
      subjects) of the sample. Cognitively, the rs405509 risk allele (TT) carriers
      showed decreased attention and execution functions compared with noncarriers
      (GG/GT). Regarding the topological alterations of the brain connectome, the risk
      allele group exhibited reduced global and local efficiency of white matter
      structural networks, mainly in the left anterior and posterior cingulate cortices
      (PCC). Importantly, the efficiency of the left PCC is correlated with the
      impaired attention function and mediates the impacts of the rs405509 genotype on
      attention. These results demonstrated that the rs405509 polymorphism affects
      attention function in nondemented elderly people, possibly by modulating brain
      structural connectivity of the PCC. This polymorphism may help us to understand
      the neural mechanisms of cognitive aging and to serve as a potential marker
      assessing the risk of AD.

PMID- 26314835
TI  - ST2 receptor invalidation maintains wound inflammation, delays healing and
      increases fibrosis.

PMID- 26314836
TI  - Vitamin K deficiency leads to exacerbation of murine dextran sulfate sodium
      induced colitis.
AB  - BACKGROUND: Patients with inflammatory bowel disease (IBD) often exhibit vitamin
      K deficiency. Vitamin K has been shown to inhibit inflammation via interleukin
      (IL)-6 suppression. This study aimed to evaluate the effect of vitamin K in a
      murine model of colitis. METHODS: Colitis was induced using dextran sulfate
      sodium (DSS) in mice fed either a vitamin K-deficient (K-def) or a vitamin K
      supplemented (K-sup) diet. The clinical and histological severity of colitis was
      assessed, and levels of cytokine production from the spleen and colonic lamina
      propria were measured by enzyme-linked immunosorbent assay and quantitative real
      time reverse transcription polymerase chain reaction. Cytokine expression levels
      in CD4(+), CD11b(+), and CD19(+) cells in the presence and absence of vitamin K
      [menatetrenone (MK-4)] were measured in vitro and apoptosis was determined by
      caspase 3/7 activity and Annexin V staining. RESULTS: DSS administration resulted
      in significantly more severe body weight loss, shorter colon length, and higher
      histological scores in mice fed a K-def diet than those fed a K-sup diet. IL-6
      expression in lamina propria mononuclear cells was significantly higher in the K
      def group than in the K-sup group. IL-6 expression was significantly decreased in
      the presence of MK-4 in CD19(+) cells, but not in the CD4(+) and CD11b(+)
      subpopulations. Apoptotic cell population in CD19(+) cells was increased in the
      presence of MK-4 in vitro and in vivo. CONCLUSIONS: Vitamin K exerts a protective
      effect against DSS colitis; this effect is associated with IL-6 downregulation.
      Vitamin K could be a potential treatment target for IBD.

PMID- 26314838
TI  - Reply to the letter by Fujishiro et al. concerning "Controversy regarding gastric
      cancer and diabetes".

PMID- 26314837
TI  - Prevalence of nonalcoholic steatohepatitis in Japanese patients with morbid
      obesity undergoing bariatric surgery.
AB  - BACKGROUND: Patients with morbid obesity selected for bariatric surgery have a
      high prevalence of nonalcoholic steatohepatitis (NASH); however, the incidence is
      varied and depends on race. The prevalence of NASH in obese Japanese patients is
      unknown. We evaluated the prevalence of NASH in a prospective cohort of Japanese
      patients with morbid obesity. METHODS: From October 2009 to July 2011,
      consecutive patients requiring bariatric surgery underwent a liver biopsy during
      the operation. The indications for bariatric surgery followed the guidelines of
      the Asia-Pacific Metabolic and Bariatric Surgery Society. RESULTS: One hundred
      two patients (55 males and 47 females, age 42.7 +/- 10.7 years) were analyzed.
      The mean body mass index was 42.1 +/- 8.2 kg/m(2). Among the 102 patients, 84
      patients (82.4%) had nonalcoholic fatty liver disease and 79 patients (77.5%) had
      NASH. The grading and staging of NASH by Brunt's classification were as follows:
      grade 0 steatosis, one patient; grade 1 steatosis, 35 patients; grade 2
      steatosis, 32 patients; grade 3 steatosis, 11 patients; stage 1 fibrosis, 25
      patients; stage 2 fibrosis, 38 patients; stage 3 fibrosis, 16 patients, stage 4
      fibrosis, no patients. The body weight, waist-hip ratio, visceral fat area, and
      aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl
      transpeptidase, fasting plasma glucose, fasting plasma insulin, C peptide,
      hemoglobin A1c, and homeostasis model assessment insulin resistance levels were
      significantly elevated in the NASH group in comparison with the non-NASH group.
      The platelet count was significantly decreased in the NASH group. The waist-hip
      ratio and the alanine aminotransferase, fasting plasma glucose, and homeostasis
      model assessment insulin resistance levels were found to be independent
      predictors of NASH in a multivariate analysis. CONCLUSION: The prevalence of NASH
      was 77.5% in this prospective Japanese cohort. The prevalence of NASH in Japanese
      morbidly obese patients was extremely high, and early intervention should be
      undertaken.

PMID- 26314839
TI  - Monitoring of Endogenous Hydrogen Sulfide in Living Cells Using Surface-Enhanced
      Raman Scattering.
AB  - Hydrogen sulfide (H2 S) has emerged as an important gasotransmitter in diverse
      physiological processes, although many aspects of its roles remain unclear,
      partly owing to a lack of robust analytical methods. Herein we report a novel
      surface-enhanced Raman scattering (SERS) nanosensor, 4-acetamidobenzenesulfonyl
      azide-functionalized gold nanoparticles (AuNPs/4-AA), for detecting the
      endogenous H2 S in living cells. The detection is accomplished with SERS spectrum
      changes of AuNPs/4-AA resulting from the reaction of H2 S with 4-AA on AuNPs. The
      SERS nanosensor exhibits high selectivity toward H2 S. Furthermore, AuNPs/4-AA
      responds to H2 S within 1 min with a 0.1 MUM level of sensitivity. In particular,
      our SERS method can be utilized to monitor the endogenous H2 S generated in
      living glioma cells, demonstrating its great promise in studies of
      pathophysiological pathways involving H2 S. 

PMID- 26314840
TI  - Buckle up! Transposon mutagenesis can differentiate melanoma drivers from their
      many passengers.

PMID- 26314841
TI  - Awareness, knowledge and views of off-label prescribing in children: a systematic
      review.
AB  - AIM: The aim of this review was to provide an updated overview of awareness,
      knowledge and views of off-label prescribing in children. METHOD: A literature
      search using electronic databases including PubMed, Medline, Scopus, Science
      Direct, Springer Link, Proquest, Ebsco Host and Google Scholar was conducted.
      Additional articles were identified by reviewing the bibliography of retrieved
      articles. The articles were searched with any of the following medical subject
      headings (MeSH) terms in the title: attitude, awareness, knowledge, experience,
      view, off-label, pediatric, paediatric and children. The inclusion criteria were
      full text articles published in English between January 2004 and February 2015
      and reported outcome related to awareness, knowledge and views regarding off
      label prescribing in children. Editorials, reviews, notes, conference
      proceedings, letters and studies reporting prevalence of off-label prescribing
      were excluded. The articles were scrutinized using thematic analysis. RESULTS:
      Eleven studies conducted among doctors, community pharmacists, paediatric nurses,
      parents and children met the inclusion criteria. Nine themes were developed
      through document analysis which included main domains such as knowledge,
      awareness and views on off-label drug use in children, choice of information
      sources, reasons and suggestions to reduce off-label prescribing, concern
      regarding obtaining consent and participation in clinical trials. CONCLUSION: The
      studies reviewed reported that the majority of doctors and community pharmacists
      were familiar with the term off-label prescribing but knowledge among parents was
      low. Awareness on off-label prescribing in children remains low among all study
      participants. There is a mismatch between views on off-label prescribing in
      children of study participants and the finding of previous studies.

PMID- 26314842
TI  - Host genotype and tumor phenotype of chemokine decoy receptors integrally affect
      breast cancer relapse.
AB  - PURPOSE: Chemokines may play vital roles in breast cancer progression and
      metastasis. The primary members of chemokine decoy receptors (CDR), DARC and D6,
      are expressed in breast tumors and lymphatic/hematogenous vessels. CDRs
      sequestrate the pro-malignant chemokines. We hypothesized that breast cancer
      patients carrying different levels of CDR expression in tumor and/or in host
      might have differing clinical outcomes. METHODS: This prospective observational
      study measured both expression and germline genotype of DARC and D6 in 463
      primary breast cancer patients enrolled between 2004 and 2006. The endpoint was
      breast cancer relapse-free survival (RFS). RESULTS: There was a significant
      association between the co-expression of CDR (immunohistochemical expression of
      both DARC and D6) with RFS (hazard ratio [HR] of 0.32, 95% confidence interval
      [CI] 0.19 to 0.54). Furthermore, the co-genotype of two non-synonymous
      polymorphisms (with two major alleles of DARC-rs12075 and D6-rs2228468 versus the
      others) significantly related to relapse. Mechanistically, the variant-alleles of
      these two polymorphisms significantly decreased by 20-30% of CCL2/CCL5 (CDR
      ligands) levels relative to their major counterparts. Multivariate analysis
      highlighted that the co-expression and co-genotype of CDR were independent
      predictors of RFS, with HR of 0.46 (95% CI 0.27 to 0.80) and 0.56 (95% CI 0.37 to
      0.85), respectively. The addition of host CDR genetic information to tumor-based
      factors (including co-expression of CDR) improved the relapse prediction ability
      (P = 0.02 of AUC comparison). CONCLUSION: The host genotype and tumor phenotype
      of CDR integrally affect breast cancer relapse. Host-related factors should be
      considered for individualized prediction of prognosis.

PMID- 26314843
TI  - TERT promoter mutations contribute to IDH mutations in predicting differential
      responses to adjuvant therapies in WHO grade II and III diffuse gliomas.
AB  - IDH mutations frequently occur in WHO grade II and III diffuse gliomas and have
      favorable prognosis compared to wild-type tumors. However, whether IDH mutations
      in WHO grade II and II diffuse gliomas predict enhanced sensitivity to adjuvant
      radiation (RT) or chemotherapy (CHT) is still being debated. Recent studies have
      identified recurrent mutations in the promoter region of telomerase reverse
      transcriptase (TERT) in gliomas. We previously demonstrated that TERT promoter
      mutations may be promising biomarkers in glioma survival prognostication when
      combined with IDH mutations. This study analyzed IDH and TERT promoter mutations
      in 295 WHO grade II and III diffuse gliomas treated with or without adjuvant
      therapies to explore their impact on the sensitivity of tumors to genotoxic
      therapies. IDH mutations were found in 216 (73.2%) patients and TERT promoter
      mutations were found in 112 (38%) patients. In multivariate analysis, IDH
      mutations (p < 0.001) were independent prognostic factors for PFS and OS in
      patients receiving genotoxic therapies while TERT promoter mutations were not. In
      univariate analysis, IDH and TERT promoter mutations were not significant
      prognostic factors in patients who did not receive genotoxic therapies. Adjuvant
      RT and CHT were factors independently impacting PFS (RT p = 0.001, CHT p = 0.026)
      in IDH mutated WHO grade II and III diffuse gliomas but not in IDH wild-type
      group. Univariate and multivariate analyses demonstrated TERT promoter mutations
      further stratified IDH wild-type WHO grade II and III diffuse gliomas into two
      subgroups with different responses to genotoxic therapies. Adjuvant RT and CHT
      were significant parameters influencing PFS in the IDH wt/TERT mut subgroup (RT p
      = 0.015, CHT p = 0.015) but not in the IDH wt/TERT wt subgroup. Our data
      demonstrated that IDH mutated WHO grade II and III diffuse gliomas had better PFS
      and OS than their IDH wild-type counterparts when genotoxic therapies were
      administered after surgery. Importantly, we also found that TERT promoter
      mutations further stratify IDH wild-type WHO grade II and III diffuse gliomas
      into two subgroups with different responses to adjuvant therapies. Taken
      together, TERT promoter mutations may predict enhanced sensitivity to genotoxic
      therapies in IDH wild-type WHO grade II and III diffuse gliomas and may justify
      intensified treatment in this subgroup. 

PMID- 26314844
TI  - Target therapy of multiple myeloma by PTX-NPs and ABCG2 antibody in a mouse
      xenograft model.
AB  - Multiple myeloma (MM) remains to be an incurable disease. The purpose of this
      study was to evaluate the effect of ABCG2 monoclonal antibody (McAb) combined
      with paclitaxel (PTX) conjugated with Fe3O4 nanoparticles (NPs) on MM progressed
      from cancer stem cells (CSCs) in non-obese-diabetic/severe-combined
      immunodeficiency (NOD/SCID) mouse model. Mice were injected with MM CSCs as
      marked by CD138-CD34- phenotypes through tail veins. The developed MM mice were
      examined by micro-computer tomography scanning, ultrasonography and enzyme-linked
      immunosorbent analysis. These mice were then intravenously treated with different
      combinations of NPs, PTX, McAb, PTX-NPs and melphalan/prednisone once a week for
      four weeks. The injected mice developed characteristic MM-associated syndromes,
      including lytic bone lesions, renal damages and proteinuria. All the treated mice
      showed decrease in bone lesions, renal damages and anemia but increase in
      apoptosis compared with the mice treated with NPs only. In particular, the
      treatment with ABCG2 McAb plus PTX-NPs induced the strongest therapeutic response
      and had an efficacy even better than that of melphalan/prednisone, a conventional
      regimen for MM patients. These data suggest that PTX-NPs with ABCG2 McAb can be
      developed into potential treatment regimens for patients with relapsed/refractory
      MM. 

PMID- 26314845
TI  - An engineered TIMP2-based and enediyne-integrated fusion protein for targeting
      MMP-14 shows potent antitumor efficacy.
AB  - Recent studies have shown that MMP-14 is highly expressed in a panel of human
      solid tumors and poses as a potential molecular target for anticancer drugs.
      Currently, major strategies for targeted therapeutics have mainly focused on the
      use of antibody or ligand-based agents. For seeking an alternative approach, it
      is of interest to employ endogenous proteins as drug delivery carriers.
      Considering the facts that TIMP2, the tissue inhibitor of metalloproteinase 2,
      shows specific interaction with MMP-14 and that Lidamycin (LDM), an extremely
      potent cytotoxic antitumor antibiotic, consists of an apoprotein (LDP) and a
      highly active enediyne (AE); we designed and prepared a TIMP2-based and enediyne
      integrated fusion protein LDP(AE)-TIMP2 by DNA recombination and molecular
      reconstitution consecutively. Furthermore, the MMP-14 binding attributes of the
      active fusion protein were determined and its therapeutic efficacy against human
      esophageal carcinoma KYSE150 xenograft and human fibrosarcoma HT1080 xenograft
      models in nude mice was investigated. It is suggested that TIMP2, the endogenous
      and MMP-14 binding protein, might serve as a guided carrier for targeted
      therapeutics. 

PMID- 26314846
TI  - Antitumor activity of the novel multi-kinase inhibitor EC-70124 in triple
      negative breast cancer.
AB  - Disseminated triple negative breast cancer (TNBC) is an incurable disease with
      limited therapeutic options beyond chemotherapy. Therefore, identification of
      druggable vulnerabilities is an important aim. Protein kinases play a central
      role in cancer and particularly in TNBC. They are involved in many oncogenic
      functions including migration, proliferation, genetic stability or maintenance of
      stem-cell like properties. In this article we describe a novel multi-kinase
      inhibitor with antitumor activity in this cancer subtype. EC-70124 is a hybrid
      indolocarbazole analog obtained by combinatorial biosynthesis of Rebeccamycin and
      Staurosporine genes that showed antiproliferative effect and in vivo antitumoral
      activity. Biochemical experiments demonstrated the inhibition of the PI3K/mTOR
      and JAK/STAT pathways. EC-70124 mediated DNA damage leading to cell cycle arrest
      at the G2/M phase. Pathway analyses identified several deregulated functions
      including cell proliferation, migration, DNA damage, regulation of stem cell
      differentiation and reversion of the epithelial-mesenchymal transition (EMT)
      phenotype, among others. Combination studies showed a synergistic interaction of
      EC-70124 with docetaxel, and an enhanced activity in vivo. Furthermore, EC-70124
      had a good pharmacokinetic profile. In conclusion these experiments demonstrate
      the antitumor activity of EC-70124 in TNBC paving the way for the future clinical
      development of this drug alone or in combination with chemotherapy. 

PMID- 26314847
TI  - NEAT expression is associated with tumor recurrence and unfavorable prognosis in
      colorectal cancer.
AB  - Long noncoding RNAs (lncRNAs) have recently been identified to be involved in
      various diseases including cancer. NEAT1 is a recently identified lncRNA with its
      function largely unknown in human malignancy. In the present study, we
      investigated NEAT1 expression in 239 cases of clinical colorectal cancer
      specimens and matched normal tissues. Statistical methods were utilized to
      analyze the association of NEAT1 with clinical features, disease-free and overall
      survival of patients. Results showed that NEAT1 expression in colorectal cancer
      was up-regulated in 72.0% (172/239) cases compared with corresponding normal
      counterparts, and related to tumor differentiation, invasion, metastasis and TNM
      stage. Kaplan-Meier analysis proved that NEAT1 was associated with both disease
      free survival and overall survival of patients with colorectal cancer that
      patients with high NEAT1 expression tend to have unfavorable outcome. Moreover,
      cox's proportional hazards analysis showed that high NEAT1 expression was an
      independent prognostic marker of poor outcome. These results provided the first
      evidence that the expression of NEAT1 in colorectal cancer may play an oncogenic
      role in colorectal cancer differentiation, invasion and metastasis. It also
      proved that NEAT1 may serve as an indicator of tumor recurrence and prognosis of
      colorectal cancer. 

PMID- 26314848
TI  - Fatty acid synthesis and NLRP3-inflammasome.

PMID- 26314849
TI  - A novel small-molecule IAP antagonist, AZD5582, draws Mcl-1 down-regulation for
      induction of apoptosis through targeting of cIAP1 and XIAP in human pancreatic
      cancer.
AB  - Inhibitor of apoptosis proteins (IAPs) plays an important role in controlling
      cancer cell survival. IAPs have therefore attracted considerable attention as
      potential targets in anticancer therapy. In this study, we investigated the anti
      tumor effect of AZD5582, a novel small-molecule IAP inhibitor, in human
      pancreatic cancer cells. Treating human pancreatic cancer cells with AZD5582
      differentially induced apoptosis, dependent on the expression of p-Akt and p
      XIAP. Moreover, the knockdown of endogenous Akt or XIAP via RNA interference in
      pancreatic cancer cells, which are resistant to AZD5582, resulted in increased
      sensitivity to AZD5582, whereas ectopically expressing Akt or XIAP led to
      resistance to AZD5582. Additionally, AZD5582 targeted cIAP1 to induce TNF-alpha
      induced apoptosis. More importantly, AZD5582 induced a decrease of Mcl-1 protein,
      a member of the Bcl-2 family, but not that of Bcl-2 and Bcl-xL. Interestingly,
      ectopically expressing XIAP and cIAP1 inhibited the AZD5582-induced decrease of
      Mcl-1 protein, which suggests that AZD5582 elicits Mcl-1 decrease for apoptosis
      induction by targeting of XIAP and cIAP1. Taken together, these results indicate
      that sensitivity to AZD5582 is determined by p-Akt-inducible XIAP phosphorylation
      and by targeting cIAP1. Furthermore, Mcl-1 in pancreatic cancer may act as a
      potent marker to analyze the therapeutic effects of AZD5582. 

PMID- 26314850
TI  - Association of CELF2 polymorphism and the prognosis of nasopharyngeal carcinoma
      in southern Chinese population.
AB  - Nasopharyngeal carcinoma (NPC) is a malignancy with high metastatic potential and
      loco-regional recurrence. The overall survival of NPC has been limited from
      further improvement partly due to the lack of effective biomarker for accurate
      prognosis prediction and precise treatments. Here, in light of the implication of
      CELF gene family in cancer prognosis, we selected 112 tagging single nucleotide
      polymorphisms (SNPs) located in six members of the family and tested their
      associations with the clinical outcomes in a discovery cohort of 717 NPC
      patients. Survival analyses under multivariate cox proportional hazards model and
      Kaplan-Meier curve revealed five promising SNPs, which were further validated in
      another independent sample of 1,520 cases. Combined analysis revealed that SNP
      rs3740194 in CELF2 was significantly associated with the decreased risk of death
      with a Hazard ratio (HR) of 0.69 (95% confidence interval [CI] = 0.58-0.82,
      codominant model). Moreover, rs3740194 also showed a significant association with
      superior metastasis-free survival (HR = 0.69, 95% CI = 0.57-0.83, codominant
      model). Taken together, our findings suggested that genetic variant of rs3740194
      in CELF2 gene might be a valuable predictor for NPC prognosis, and potentially
      useful in the personalized treatment of NPC. 

PMID- 26314851
TI  - Na+-induced Ca2+ influx through reverse mode of Na+-Ca2+ exchanger in mouse
      ventricular cardiomyocyte.
AB  - BACKGROUND: Dobutamine is commonly used for clinical management of heart failure
      and its pharmacological effects have long been investigated as inotropics via
      beta-receptor activation. However, there is no electrophysiological evidence if
      dobutamine contributes inotropic action due at least partially to the reverse
      mode of Na+-Ca2+ exchanger (NCX) activation. METHODS: Action potential (AP),
      voltage-gated Na+ (INa), Ca2+ (ICa), and K+ (Ito and IK1) currents were observed
      using whole-cell patch technique before and after dobutamine in ventricular
      cardiomyocytes isolated from adult mouse hearts. Another sets of observation were
      also performed with Kb-r7943 or in the solution without [Ca2+]o. RESULTS:
      Dobutamine (0.1-1.0 MUM) significantly enhanced the AP depolarization with
      prolongation of AP duration (APD) in a concentration-dependent fashion. The
      density of INa was also increased concentration-dependently without alternation
      of voltage-dependent steady-status of activation and inactivation, reactivation
      as well. Whereas, the activities for ICa, Ito, and IK1 were not changed by
      dobutamine. Intriguingly, the dobutamine-mediated changes in AP repolarization
      were abolished by 3 MUM Kb-r7943 pretreatment or by simply removing [Ca2+]o
      without affecting accelerated depolarization. Additionally, the ratio of
      APD50/APD90 was not significantly altered in the presence of dobutamine, implying
      that effective refractory period was remain unchanged. CONCLUSIONS: This novel
      finding provides evidence that dobutamine upregulates of voltage-gated Na+
      channel function and Na+ influx-induced activation of the reverse mode of NCX,
      suggesting that dobutamine may not only accelerate ventricular contraction via
      fast depolarization but also cause Ca2+ influx, which contributes its positive
      inotropic effect synergistically with beta-receptor activation without increasing
      the arrhythmogenetic risk.

PMID- 26314852
TI  - OX40/OX40L axis: not a friend in autoimmunity.

PMID- 26314853
TI  - Uncovering HIV-1-infected cells.

PMID- 26314854
TI  - Predicting the molecular role of MEIS1 in esophageal squamous cell carcinoma.
AB  - The three amino acid loop extension (TALE) class myeloid ecotropic viral
      integration site 1 (MEIS1) homeobox gene is known to play a crucial role in
      normal and tumor development. In contrast with its well-described cancer stemness
      properties in hematopoietic cancers, little is known about its role in solid
      tumors like esophageal squamous cell carcinoma (ESCC). Here, we analyzed MEIS1
      expression and its clinical relevance in ESCC patients and also investigated its
      correlation with the SOX2 self-renewal master transcription factor in the ESCC
      samples and in the KYSE-30 ESCC cell line. MEIS1 mRNA and protein expression were
      significantly decreased in ESCC disease (P < 0.05). The inverse correlation
      between MEIS1 mRNA expression and tumor cell metastasis to the lymph nodes (P =
      0.004) was significant. Also, MEIS1 protein levels inversely correlated to lymph
      node involvement (P = 0.048) and high tumor stage (stages III/IV, P = 0.030). The
      low levels of DNA methylation in the MEIS1 promoter showed that this suppression
      does not depend on methylation. We showed that downregulation of EZH2 restored
      MEIS1 expression significantly. Also, we investigated that MEIS1 downregulation
      is concomitant with increased SOX2 expression. To the best of our knowledge, this
      is the first report on the MEIS1 gene in ESCC. The inverse correlation of MEIS1
      with metastasis, tumor staging, and the role of EZH2 in methylation, together
      with its correlation with stemness factor SOX2 expression, led us to predict
      cancer stemness properties for MEIS1 in ESCC. 

PMID- 26314855
TI  - Overexpression of miR-100 inhibits cancer growth, migration, and chemosensitivity
      in human NSCLC cells through fibroblast growth factor receptor 3.
AB  - Nonsmall cell lung cancer (NSCLC) is a commonly occurring lung cancer. A
      combination of molecular biological treatments with regular chemotherapy may
      result in improved therapeutic outcome. Here, we reported significantly higher
      levels of fibroblast growth factor receptor 3 (FGFR3) and significantly lower
      levels of miR-100 in the NSCLC specimen, compared to the paired NSCLC-adjacent
      normal lung tissues. Moreover, the levels of FGFR3 and miR-100 were inversely
      correlated. Bioinformatics analyses followed by luciferase reporter assay showed
      that miR-100 bound to the 3'-UTR of FGFR3 messenger RNA (mRNA) to inhibit its
      translation. Overexpression of miR-100 in NSCLC cells decreased FGFR3 protein
      levels, whereas inhibition of miR-100 increased FGFR3 protein levels, without
      affecting FGFR3 mRNA levels. Furthermore, overexpression of miR-100 suppressed
      cancer growth, migration, and chemosensitivity in NSCLC cells, while inhibition
      of miR-100 significantly facilitated them. Taken together, our data demonstrate
      that miR-100 may inhibit NSCLC through FGFR3.

PMID- 26314856
TI  - CpG methylation of ubiquitin carboxyl-terminal hydrolase 1 (UCHL1) and P53
      mutation pattern in sporadic colorectal cancer.
AB  - The ubiquitin-proteasome system plays an essential regulatory role in various
      cellular processes. Besides its involvement in normal cellular functions, the
      alteration of proteasomal activity contributes to the pathological states of
      several clinical disorders, including cancer. Aberrant methylation of the CpG
      islands has been reported as an alternative way to inactivate gene expression
      involved in the ubiquitination process and thus protein degradation in tumor
      tissues. In this study, we aimed to determine the CpG methylation pattern of the
      UCHL1 promoter, as well as the mutation spectrum and the expression pattern of
      P53 in sporadic colorectal cancer (CRC) from Tunisian patients. We found that
      UCHL1 was methylated in 68.57 % and correlated significantly with lymph node
      metastasis (P = 0.029) and transcriptional silencing in tumor tissues (P =
      0.013). Mutation screening of exons 5-9 of P53 showed that 42.85 % of cases
      harbor somatic mutation and are positively correlated with the methylated pattern
      of UCHL1 (P = 0.001). Furthermore, cytoplasmic accumulation of P53 was strongly
      associated with the unmethylated UCHL1 profile (P = 0.006), supporting the
      relationship between these two proteins in CRC. 

PMID- 26314857
TI  - Altered expression of LINC-ROR in cancer cell lines and tissues.
AB  - According to GLOBOCAN 2012, the worldwide burden of cancer increased and is
      expected to worsen within the next decades. Therefore, universal combat against
      cancer will not succeed with treatment solely; effective prevention and early
      detection are urgently needed to tackle the cancer crisis. Emerging data
      demonstrate that long non-coding RNAs are involved in numerous biological and
      pathological processes like development and differentiation and in a variety of
      human diseases including cancer. Located at 18q21, LINC-ROR (regulator of
      reprogramming) is a modulator of ESCs maintenance and hypoxia-signaling pathways
      in hepatocellular cancer cells. The aim of this study was to examine the
      expression of LINC-ROR in various cell lines and representative samples of human
      cancers by quantitative real-time RT-PCR to provide a snapshot on how LINC-ROR
      expression may be deregulated in cancer. More than 30 cell lines and 112 patient
      specimens from various tissues were assessed for relative expression of LINC-ROR.
      Our results revealed that the expression of LINC-ROR was lower in all somatic
      cancer cell lines compared to stem cells or cells with stem cell-like
      capabilities, like the embryonic carcinoma cell line, NTERA-2. In tissues,
      expression patterns vary, but some cancerous tissues displayed increased LINC-ROR
      expression compared to corresponding normal tissues. Thus, we hypothesize that
      LINC-ROR may have a key function in a subpopulation of cells from the tumor bulk,
      i.e., the cancer stem cells associated with specific properties including
      resistance to adverse environmental conditions. 

PMID- 26314858
TI  - Influences of ERCC1, ERCC2, XRCC1, GSTP1, GSTT1, and MTHFR polymorphisms on
      clinical outcomes in gastric cancer patients treated with EOF chemotherapy.
AB  - This study investigated the associations between genetic polymorphisms of six
      genes involved in DNA repair, detoxification pathways, and fluoropyrimidine
      metabolism and clinical outcomes in MGC patients receiving EOF treatment. This
      retrospective study included 108 Chinese MGC patients receiving EOF as first-line
      chemotherapy. Nine single nucleotide polymorphisms (SNPs) of six genes (ERCC1
      rs2298881, ERCC2 rs13181 and rs1799793, XRCC1 rs25487 and rs25489, GSTP1 rs1695,
      GSTT1 rs2266637, and MTHFR rs1801133 and rs1801131) were genotyped, and the
      associations between each SNP and clinical outcome were analyzed. XRCC1 rs25487 A
      allele was significantly associated with progression disease (PD) to EOF (p =
      0.002), and patients with AA genotype had significantly poorer progression-free
      survival (PFS) (p = 0.001) and overall survival (OS) (p = 0.041) compared with
      patients with the G allele (GG + GA). ERCC2 rs13181 G allele was significantly
      associated with PD (p = 0.026), and G carriers (GG + GT) tended to have poorer
      PFS (p = 0.092) than TT homozygotes. ERCC2 rs1799793 GA genotype was associated
      with unfavorable PFS (p = 0.034) and a tendency toward poorer OS (p = 0.090)
      compared with GG homozygotes. Patients were categorized as either good (0 risk
      factors) or poor risk (>=1 unfavorable SNPs) using a prognostic index based on
      XRCC1 rs25487 AA, ERCC2 rs13181 (GG + GT), and ERCC2 rs1799793 GA genotypes, with
      median OS and PFS of 534 days, 281 days (p = 0.009) and 206 days, and 123 days (p
      < 0.001), respectively. These results suggest that the prognostic index
      comprising XRCC1 rs25487, ERCC2 rs13181, and rs1799793 polymorphisms may be a
      useful predictor of clinical outcomes in MGC treated with EOF. 

PMID- 26314860
TI  - Erratum to: Exon 19 deletion of epidermal growth factor receptor is associated
      with prolonged survival in brain metastases from non-small-cell lung cancer.

PMID- 26314859
TI  - miR-15a enhances the anticancer effects of cisplatin in the resistant non-small
      cell lung cancer cells.
AB  - Platinum-based chemotherapies have long been used as a standard treatment in non
      small cell lung cancer. However, cisplatin resistance is a major problem that
      restricts the use of cisplatin. Deregulated cell death mechanisms including
      apoptosis and autophagy could be responsible for the development of cisplatin
      resistance and miRNAs are the key regulators of these mechanisms. We aimed to
      analyse the effects of selected miRNAs in the development of cisplatin resistance
      and found that hsa-miR-15a-3p was one of the most significantly downregulated
      miRNAs conferring resistance to cisplatin in Calu1 epidermoid lung carcinoma
      cells. Only hsa-miR-15a-3p mimic transfection did not affect cell proliferation
      or cell death, though decreased cell viability was found when combined with
      cisplatin. We found that induced expression of hsa-miR-15a-3p via mimic
      transfection sensitised cisplatin-resistant cells to apoptosis and autophagy. Our
      results demonstrated that the apoptosis- and autophagy-inducing effects of hsa
      miR-15a-3p might be due to suppression of BCL2, which exhibits a major connection
      with cell death mechanisms. This study provides new insights into the mechanism
      of cisplatin resistance due to silencing of the tumour suppressor hsa-miR-15a-3p
      and its possible contribution to apoptosis, autophagy and cisplatin resistance,
      which are the devil's triangle in determining cancer cell fate. 

PMID- 26314861
TI  - Aspirin and salicylic acid decrease c-Myc expression in cancer cells: a potential
      role in chemoprevention.
AB  - Epidemiological studies have demonstrated a significant correlation between
      regular aspirin use and reduced colon cancer incidence and mortality; however,
      the pathways by which it exerts its anti-cancer effects are still not fully
      explored. We hypothesized that aspirin's anti-cancer effect may occur through
      downregulation of c-Myc gene expression. Here, we demonstrate that aspirin and
      its primary metabolite, salicylic acid, decrease the c-Myc protein levels in
      human HCT-116 colon and in few other cancer cell lines. In total cell lysates,
      both drugs decreased the levels of c-Myc in a concentration-dependent fashion.
      Greater inhibition was observed in the nucleus than the cytoplasm, and
      immunofluorescence studies confirmed these observations. Pretreatment of cells
      with lactacystin, a proteasome inhibitor, partially prevented the downregulatory
      effect of both aspirin and salicylic acid, suggesting that 26S proteasomal
      pathway is involved. Both drugs failed to decrease exogenously expressed DDK
      tagged c-Myc protein levels; however, under the same conditions, the endogenous c
      Myc protein levels were downregulated. Northern blot analysis showed that both
      drugs caused a decrease in c-Myc mRNA levels in a concentration-dependent
      fashion. High-performance liquid chromatography (HPLC) analysis showed that
      aspirin taken up by cells was rapidly metabolized to salicylic acid, suggesting
      that aspirin's inhibitory effect on c-Myc may occur through formation of
      salicylic acid. Our result suggests that salicylic acid regulates c-Myc level at
      both transcriptional and post-transcription levels. Inhibition of c-Myc may
      represent an important pathway by which aspirin exerts its anti-cancer effect and
      decrease the occurrence of cancer in epithelial tissues. 

PMID- 26314862
TI  - Toward an understanding of the role of a catechol moiety in cancer
      chemoprevention: The case of copper- and o-quinone-dependent Nrf2 activation by a
      catechol-type resveratrol analog.
AB  - SCOPE: Catechol moieties are commonly present in dietary natural products that
      exert cancer chemopreventive activity. While the oxidative conversion of
      catechols into their corresponding o-quinones is generally considered to
      contribute to their cancer chemopreventive effects, the mechanism of the
      intracellular conversion has not been fully elucidated. METHODS AND RESULTS:
      Among resveratrol and its hydroxylated analogs examined, only 3,4-dihydroxy-trans
      stilbene exerted cytoprotective effects against t-butylhydroperoxide-induced
      death of HepG2 cells. This resveratrol analog activated the nuclear factor
      erythroid-2-related factor 2 (Nrf2) pathway through stimulating phosphorylation
      of Akt and inducing keap1 modification, thereby resulting in its nuclear
      translocation and subsequent transcriptional induction of phase II detoxifying
      enzymes. Its cytoprotective effect through Nrf2 activation was largely abrogated
      by pretreatment of cells with DTT, a sulfhydryl-containing nucleophile, and
      neocuproine, a specific chelating agent for copper ions. CONCLUSION: We
      identified 3,4-dihydroxy-trans-stilbene as a novel Nrf2 activator that is
      converted intracellularly into its corresponding o-quinone electrophile by copper
      ions. The copper-mediated oxidation was required for the Nrf2 activation,
      subsequent transcriptional induction of phase II detoxifying enzymes and
      ultimately for cytoprotection. The findings demonstrate a previously
      underrecognized role for intracellular copper ions in the cancer chemopreventive
      effects of catechol-containing dietary natural products.

PMID- 26314863
TI  - Correction: Structural basis for the prion-like MAVS filaments in antiviral
      innate immunity.

PMID- 26314864
TI  - Distinct transcriptional responses elicited by unfolded nuclear or cytoplasmic
      protein in mammalian cells.
AB  - Eukaryotic cells possess a variety of signaling pathways that prevent
      accumulation of unfolded and misfolded proteins. Chief among these is the heat
      shock response (HSR), which is assumed to respond to unfolded proteins in the
      cytosol and nucleus alike. In this study, we probe this axiom further using
      engineered proteins called 'destabilizing domains', whose folding state we
      control with a small molecule. The sudden appearance of unfolded protein in
      mammalian cells elicits a robust transcriptional response, which is distinct from
      the HSR and other known pathways that respond to unfolded proteins. The cellular
      response to unfolded protein is strikingly different in the nucleus and the
      cytosol, although unfolded protein in either compartment engages the p53 network.
      This response provides cross-protection during subsequent proteotoxic stress,
      suggesting that it is a central component of protein quality control networks,
      and like the HSR, is likely to influence the initiation and progression of human
      pathologies. 

PMID- 26314866
TI  - Beneficial effects of blood group antigen synthesis-increasing natural plant
      extracts and monosaccharides on extracellular matrix protein production in vivo.

PMID- 26314865
TI  - Chemical perturbation of an intrinsically disordered region of TFIID
      distinguishes two modes of transcription initiation.
AB  - Intrinsically disordered proteins/regions (IDPs/IDRs) are proteins or peptide
      segments that fail to form stable 3-dimensional structures in the absence of
      partner proteins. They are abundant in eukaryotic proteomes and are often
      associated with human diseases, but their biological functions have been elusive
      to study. In this study, we report the identification of a tin(IV) oxochloride
      derived cluster that binds an evolutionarily conserved IDR within the metazoan
      TFIID transcription complex. Binding arrests an isomerization of promoter-bound
      TFIID that is required for the engagement of Pol II during the first (de novo)
      round of transcription initiation. However, the specific chemical probe does not
      affect reinitiation, which requires the re-entry of Pol II, thus, mechanistically
      distinguishing these two modes of transcription initiation. This work also
      suggests a new avenue for targeting the elusive IDRs by harnessing certain
      features of metal-based complexes for mechanistic studies, and for the
      development of novel pharmaceutical interventions. 

PMID- 26314867
TI  - Tobacco Policies in Louisiana: Recommendations for Future Tobacco Control
      Investment from SimSmoke, a Policy Simulation Model.
AB  - Despite the presence of tobacco control policies, Louisiana continues to
      experience a high smoking burden and elevated smoking-attributable deaths. The
      SimSmoke model provides projections of these health outcomes in the face of
      existing and expanded (simulated) tobacco control polices. The SimSmoke model
      utilizes population data, smoking rates, and various tobacco control policy
      measures from Louisiana to predict smoking prevalence and smoking-attributable
      deaths. The model begins in 1993 and estimates are projected through 2054. The
      model is validated against existing Louisiana smoking prevalence data. The most
      powerful individual policy measure for reducing smoking prevalence is cigarette
      excise tax. However, a comprehensive cessation treatment policy is predicted to
      save the most lives. A combination of tobacco control policies provides the
      greatest reduction in smoking prevalence and smoking-attributable deaths. The
      existing Louisiana excise tax ranks as one of the lowest in the country and the
      legislature is against further increases. Alternative policy measures aimed at
      lowering prevalence and attributable deaths are: cessation treatments,
      comprehensive smoke-free policies, and limiting youth access. These three
      policies have a substantial effect on smoking prevalence and attributable deaths
      and are likely to encounter more favor in the Louisiana legislature than
      increasing the state excise tax. 

PMID- 26314868
TI  - The SOS Suicide Prevention Program: Further Evidence of Efficacy and
      Effectiveness.
AB  - This study replicated and extended previous evaluations of the Signs of Suicide
      (SOS) prevention program in a high school population using a more rigorous pre
      test post-test randomized control design than used in previous SOS evaluations in
      high schools (Aseltine and DeMartino 2004; Aseltine et al. 2007). SOS was
      presented to an ethnically diverse group of ninth grade students in technical
      high schools in Connecticut. After controlling for the pre-test reports of
      suicide behaviors, exposure to the SOS program was associated with significantly
      fewer self-reported suicide attempts in the 3 months following the program. Ninth
      grade students in the intervention group were approximately 64% less likely to
      report a suicide attempt in the past 3 months compared with students in the
      control group. Similarly, exposure to the SOS program resulted in greater
      knowledge of depression and suicide and more favorable attitudes toward (1)
      intervening with friends who may be exhibiting signs of suicidal intent and (2)
      getting help for themselves if they were depressed or suicidal. In addition, high
      risk SOS participants, defined as those with a lifetime history of suicide
      attempt, were significantly less likely to report planning a suicide in the 3
      months following the program compared to lower-risk participants. Differential
      attrition is the most serious limitation of the study; participants in the
      intervention group who reported a suicide attempt in the previous 3 months at
      baseline were more likely to be missing at post-test than their counterparts in
      the control group.

PMID- 26314869
TI  - Effects of Acetylsalicylic Acid Usage on Inflammatory and Oxidative Stress
      Markers in Hemodialysis Patients.
AB  - The aims of this study were to determine the effects of acetylsalicylic acid
      (ASA) on inflammation and oxidative stress markers in hemodialysis (HD) patients
      and to examine the associations between these markers and the sociodemographic
      and clinical characteristics of participants. The study included 36 subjects who
      used 300 mg of ASA for 60 days. Inflammation and oxidative stress were assessed
      based on levels of biochemical markers. ASA usage promoted a decrease in high
      sensitivity C-reactive protein (p = 0.01). The level of hydrogen peroxide
      increased after 30 days of use of ASA and subsequently decreased (p = 0.01).
      Reduced glutathione reduced at the end of the study (p < 0.01); the
      malondialdehyde level did not change and the levels of vitamins A and E were
      inverse to drug use (p = 0.01). ASA usage promoted reduced levels of
      inflammation, increased production of markers of oxidative stress, and reduced
      antioxidant defense.

PMID- 26314870
TI  - Evaluation of Apelin and Insulin Resistance in Patients with PCOS and Therapeutic
      Effect of Drospirenone-Ethinylestradiol Plus Metformin.
AB  - BACKGROUND: The aim of this study was to determine the relevance of apelin and
      insulin resistance (IR) with polycystic ovary syndrome (PCOS) and to assess the
      possible therapeutic effect of the combined therapy of drospirenone
      ethinylestradiol (DRSP-EE) combined with metformin. MATERIAL AND METHODS: Sixty
      three PCOS patients and 40 non-PCOS infertile patients were recruited. The
      fasting serum levels of follicle stimulating hormone (FSH), luteinizing hormone
      (LH), testosterone (T), prolactin (PRL), estradiol (E2), glucose (FBG), insulin
      (FINS), and apelin at the early follicular phase were measured. To further
      investigate the relation between apelin and IR, we treated the PCOS patients with
      DRSP-EE (1 tablet daily, 21 d/month) plus metformin (500 mg tid) for 3 months.
      All of the above indices were measured again after treatment. RESULTS: 1) Levels
      of apelin, LH, LH/FSH, T, and FINS, as well as homeostatic model assessment of IR
      (HOMA-IR) in PCOS patients, were significantly higher than in the control group
      before treatment. 2) These indices significantly decreased after treatment with
      DRSP-EE plus metformin. 3) Correlation analysis showed that apelin level was
      positively correlated with body mass index (BMI), FINS level, and HOMA-IR.
      CONCLUSIONS: Apelin level significantly increased in PCOS patients. The combined
      therapy of DRSP-EE plus metformin not only decreases IR, but also improves apelin
      level. This combination is a superior approach for PCOS treatment.

PMID- 26314871
TI  - Lateralization of infant holding by mothers: A longitudinal evaluation of
      variations over the first 12 weeks.
AB  - The maternal preference to hold infants on the left rather than right side of the
      body was examined longitudinally, with attention to 4 explanations: maternal
      monitoring of infant state, maternal handedness, infant proximity to the mother's
      heartbeat, and preferred infant head position. The side and site of holding were
      measured over the first 12 weeks of the lives of 24 infants. Information about
      group and individual consistency in holding side allowed novel evaluation of the
      theories. A strong bias to hold on the left dropped below significance when the
      infants were aged 12 weeks and was limited to specific holding positions.
      Findings were generally consistent with the monitoring hypothesis, and little
      support was found for the 3 alternative explanations. 

PMID- 26314873
TI  - Tricuspid Regurgitation: 2015 Reflections and Re-evaluation.
AB  - OPINION STATEMENT: The tricuspid valve is, in fact, anatomically and functionally
      more complex than its left-sided counterpart-the mitral valve. Patients may
      develop tricuspid regurgitation from a variety of mechanisms. While current
      guidelines provide a very basic approach to tricuspid regurgitation (TR)
      evaluation, more recent techniques, particularly 3D echocardiography, have
      provided novel insights into how we can ascertain the mechanism and severity of
      tricuspid regurgitation, how the tricuspid valve adapts to disease and,
      importantly, how we assess the effects of TR on right ventricular size and
      function. We anticipate that these advances will soon yield dividends that will
      help us decide on approaches to treatment and timing of surgery.

PMID- 26314872
TI  - Endovascular treatment of cerebral aneurysms using flow-diverter devices: A
      systematic review.
AB  - BACKGROUND: Flow-diverter devices (FDDs) are new-generation stents placed in the
      parent artery at the level of the aneurysm neck to disrupt the intra-aneurysmal
      flow thus favoring intra-aneurysmal thrombosis. OBJECTIVE: The objective of this
      review article is to define the indication and results of the treatment of
      intracranial aneurysms by FDD, reviewing 18 studies of endovascular treatment by
      FDDs for a total of 1704 aneurysms in 1483 patients. METHODS: The medical
      literature on FDDs for intracranial aneurysms was reviewed from 2009 to December
      2014. The keywords used were: "intracranial aneurysms," "brain aneurysms," "flow
      diverter," "pipeline embolization device," "silk flow diverter," "surpass flow
      diverter" and "FRED flow diverter." RESULTS: The use of these stents is advisable
      mainly for unruptured aneurysms, particularly those located at the internal
      carotid artery or vertebral and basilar arteries, for fusiform and dissecting
      aneurysms and for saccular aneurysms with large necks and low dome-to-neck ratio.
      The rate of aneurysm occlusion progressively increases during follow-up (81.5%
      overall rate in this review). The non-negligible rate of ischemic (mean 4.1%) and
      hemorrhagic (mean 2.9%) complications, the neurological morbidity (mean 3.5%) and
      the reported mortality (mean 3.4%) are the main limits of this technique.
      CONCLUSION: Treatment with FDDs is a feasible and effective technique for
      unruptured aneurysms with complex anatomy (fusiform, dissecting, large neck,
      bifurcation with side branches) where coiling and clipping are difficult or
      impossible. Patient selection is very important to avoid complications and reduce
      the risk of morbidity and mortality. Further studies with longer follow-up are
      necessary to define the rate of complete occlusion.

PMID- 26314874
TI  - [From the project to standard care. The correct assessment of the benefits of
      telemedicine has a key role].
AB  - The reason for this contribution is the hesitant dissemination of telemedicine
      procedures in the healthcare system. Because of missing benefits there are few
      incentives for players to use telemedicine procedures in the interest of
      patients.It is the aim of the work to open a discussion that differentiates the
      framework for the benefit assessment of telemedicine along certain criteria. The
      intention is to create a tool that helps to speed up necessary decisions in the
      committees responsible.This work develops a new categorization for telemedicine
      applications by differentiating between the medical model and the technical
      process of telemedicine application. The categories refer to the medical and
      economic risk level of the applications. Only applications with highest risk
      must, therefore, be evaluated by RCT surveys. 

PMID- 26314875
TI  - Prognostic Value of the Circumferential Resection Margin in Esophageal Cancer
      Patients After Neoadjuvant Chemoradiotherapy.
AB  - BACKGROUND: Circumferential resection margins (CRM) for esophageal cancer (EC),
      defined by the College of American Pathologists (CAP; >0 mm) or the Royal College
      of Pathologists (RCP; >1 mm) as tumor-free (R0), are based on a surgery-alone
      approach. We evaluated the usefulness of both definitions in current practice
      with neoadjuvant chemoradiotherapy (nCRT). METHODS: CRMs were measured in 209
      patients (104 with nCRT) with locally advanced EC after transthoracic
      esophagectomy. Local recurrence and cancer related death were scored as events.
      Patients were followed for at least 2 years or until death. Prognostic factors (P
      < 0.1 in univariate analyses) for 2-year disease-free survival (DFS) and local
      recurrence-free survival (LRFS) were incorporated in multivariate Cox regression
      analyses. Both CRM measurements were analyzed separately and prognostic cutoff
      values (0-1.0 mm) were assessed in both groups. RESULTS: Independent prognostic
      factors (P < 0.05) for 2-year DFS were tumor length, lymph node ratio,
      angioinvasion, and CAP R0 in the surgery-alone group and pN stage (P < 0.01) in
      the nCRT group. Prognostic factors (P < 0.05) for 2-year LRFS were CAP, lymph
      node ratio, and tumor length in the surgery-alone group, and CAP and grade in the
      nCRT group. Optimal CRM cutoff values between 0.0 and 0.2 mm were prognostic for
      2-year DFS in the surgery-alone and at 0.3 mm for the nCRT group. CONCLUSIONS:
      nCRT affected the CRM cutoff values. After nCRT, the CRM R0 according to the CAP
      was only prognostic for 2-year LRFS. However, in the surgery-alone group, it was
      prognostic for both the 2-year DFS and LRFS.

PMID- 26314877
TI  - Rating competency in everyday activities in patients with TBI: clinical insights
      from a close look at patient-family differences.
AB  - PURPOSE: Families of patients with traumatic brain injury (TBI) often perceive
      patients' functional capabilities differently from patients themselves. Research
      documents inconsistent findings regarding direction of differences. Differences
      have implications for family support and are germane to clinicians' treatment
      planning during rehabilitation. We compared two analytic approaches to patient
      family differences in ratings of 30 functional tasks: (a) comparing patients' and
      families' mean scores in domains derived from factor analysis versus (b)
      examining differences on a task-by-task basis. METHOD: In-home interviews were
      conducted with 83 outpatients with TBI at a Veteran Affairs polytrauma clinic and
      for each a family member, using the Patient Competency Rating Scale with both.
      RESULTS: Principal components analysis identified three functional domains-
      cognitive, interpersonal/emotional and physical--with significant patient-family
      differences in the cognitive domain only (family competency ratings were higher).
      By contrast, task-by-task examination showed significant veteran-family
      differences in 12 items, mostly in interpersonal/emotional functioning, with
      mixed directions of differences. The task-by-task approach thus revealed a
      different picture of patient-family differences than examination by functional
      domains. CONCLUSIONS: Grouping tasks by domains may obscure important differences
      in functional ratings. Examination of patient-family differences by task has
      clinical applications for helping patients and families to manage TBI symptoms
      and for treatment planning. IMPLICATIONS FOR REHABILITATION: Differences in
      functional capacity ratings by patients with TBI and their family members are not
      well understood, with past research demonstrating inconsistencies in direction of
      difference. Differences in ratings may affect family relationships and may inform
      clinicians' treatment plans. The study showed that different approaches to
      analyzing the same data yield two distinct pictures of patient-family
      differences. Examining patient-family differences by specific tasks is clinically
      meaningful. The Competency Rating Scale could be used as a clinical tool with
      patients and families. Its use may improve family understanding of the patient's
      strengths and struggles and also guide treatment planning.

PMID- 26314876
TI  - Prognostic Performance of Current Stage III Oral Cancer Patients After Curative
      Intent Resection: Evidence to Support a Revision of the American Joint Committee
      on Cancer Staging System.
AB  - BACKGROUND: The American Joint Committee on Cancer (AJCC) stage III
      classification of oral cavity squamous cell carcinoma (OCSCC) represents a
      heterogeneous group of patients with early local disease with regional metastases
      (T1N1 and T2N1) and advanced local disease with or without regional metastasis
      (T3N0 and T3N1). OBJECTIVE: The aim of this study was to evaluate prognostic
      heterogeneity in the stage III category. METHODS AND PATIENTS: An international
      retrospective multicenter study of 1815 patients who were treated for OCSCC from
      2003 to 2011. RESULTS: Kaplan-Meier survival analysis and multivariate models of
      stage III patients revealed better overall survival (OS; HR 2.12, 95 % CI 1.03
      4.15; p = 0.01) and disease-specific survival (DSS; HR 1.7, 95 % CI 1.16-4.12; p
      = 0.04) rates for patients with T1-2N1/T3N0 disease than for patients with T3N1
      disease. The outcomes of patients with T3N1 and stage IVa disease were similar (p
      = 0.89 and p = 0.78 for OS and DSS, respectively). Modifying stage classification
      by transferring the T3N1 category to the stage VIa group resulted in a better
      prognostic performance [Harrell's concordance index, C index 0.76; Akaike's
      Information Criterion (AIC) 4131.6] compared with the AJCC 7th edition staging
      system (C index 0.65; AIC 4144.9) for OS. When DSS was assessed, the suggested
      staging system remained the best performing model (C index 0.71; AIC 1061.3)
      compared with the current AJCC 7th edition staging (C index 0.64; AIC 1066.2).
      CONCLUSIONS: The prognosis of T3N1 and stage IVa disease are similar in OCSCC,
      suggesting that these categories could be combined in future revisions of the
      nodal staging system to enhance prognostic accuracy.

PMID- 26314878
TI  - The Chronic Detrimental Impact of Interruptions in a Simulated Submarine Track
      Management Task.
AB  - OBJECTIVE: The objective of this article is to examine the extent to which
      interruptions negatively impact situation awareness and long-term performance in
      a submarine track management task where pre- and postinterruption display scenes
      remained essentially identical. BACKGROUND: Interruptions in command and control
      task environments can degrade performance well beyond the first postinterruption
      action typically measured for sequential static tasks, because individuals need
      to recover their situation awareness for multiple unfolding display events.
      Participants in the current study returned to an unchanged display scene
      following interruption and therefore could be more immune to such long-term
      performance deficits. METHOD: The task required participants to monitor a display
      to detect contact heading changes and to make enemy engagement decisions.
      Situation awareness (Situation Present Assessment Method) and subjective workload
      (NASA-Task Load Index) were measured. The interruption replaced the display for
      20 s with a blank screen, during which participants completed a classification
      task. RESULTS: Situation awareness after returning from interruption was
      degraded. Participants were slower to make correct engagement decisions and
      slower and less accurate in detecting heading changes, despite these task
      decisions being made at least 40 s following the interruption. CONCLUSION:
      Interruptions negatively impacted situation awareness and long-term performance
      because participants needed to redetermine the location and spatial relationship
      between the displayed contacts when returning from interruption, either because
      their situation awareness for the preinterruption scene decayed or because they
      did not encode the preinterruption scene. APPLICATION: Interruption in work
      contexts such as submarines is unavoidable, and further understanding of how
      operators are affected is required to improve work design and training.

PMID- 26314879
TI  - Intracranial hemorrhage following surgery for occult spinal dysraphism. Reply to
      E.M.J. Cornips and J. van Aalts' letter to the editor.

PMID- 26314880
TI  - Litigation trends and costs in otorhinolaryngology.
AB  - BACKGROUND: Litigation in surgery is increasing and liabilities are becoming
      unsustainable. This study aimed to analyse trends in claims, and identify areas
      for potential risk reduction, improved patient safety and a reduction in the
      number, and cost, of future claims. METHODS: Ten years of retrospective data on
      claims in otorhinolaryngology (2003-2013) were obtained from the National Health
      Service Litigation Authority via a Freedom of Information request. Data were re
      entered into a spreadsheet and coded for analysis. RESULTS: A total of 1031
      claims were identified; of these, 604 were successful and 427 were unsuccessful.
      Successful claims cost a total of L41 000 000 (mean, L68 000). The most common
      areas for successful claims were: failure or delay in diagnosis (137 cases),
      intra-operative problems (116 cases), failure or delay in treatment (66 cases),
      failure to warn - informed consent issue (54 cases), and inappropriate treatment
      (47 cases). CONCLUSION: Over half of the claims in ENT relate to the five most
      common areas of liability. Recent policy changes by the National Health Service
      Litigation Authority, over the level of information divulged, limits our learning
      from claims.

PMID- 26314881
TI  - Early rehabilitation using a passive cycle ergometer on muscle morphology in
      mechanically ventilated critically ill patients in the Intensive Care Unit (MoVe
      ICU study): study protocol for a randomized controlled trial.
AB  - BACKGROUND: Patients in Intensive Care Units (ICU) are often exposed to prolonged
      immobilization which, in turn, plays an important role in neuromuscular
      complications. Exercise with a cycle ergometer is a treatment option that can be
      used to improve the rehabilitation of patients on mechanical ventilation (MV) in
      order to minimize the harmful effects of immobility. METHODS/DESIGN: A single
      blind randomized controlled trial (the MoVe ICU study) will be conducted to
      evaluate and compare the effects of early rehabilitation using a bedside cycle
      ergometer with conventional physical therapy on the muscle morphology of the knee
      extensors and diaphragm in critical ill patients receiving MV. A total of 28
      adult patients will be recruited for this study from among those admitted to the
      intensive care department at the Hospital de Clinicas de Porto Alegre. Eligible
      patients will be treated with MV from a period of 24 to 48 h, will have spent
      maximum of 1 week in hospital and will not exhibit any characteristics
      restricting lower extremity mobility. These subjects will be randomized to
      receive either conventional physiotherapy or conventional physiotherapy with an
      additional cycle ergometer intervention. The intervention will be administered
      passively for 20 min, at 20 revolutions per minute (rpm), once per day, 7 days a
      week, throughout the time the patients remain on MV. Outcomes will be cross
      sectional quadriceps thickness, length of fascicle, pennation angle of fascicles,
      thickness of vastus lateralis muscle, diaphragm thickness and excursion of
      critical ICU patients on MV measured with ultrasound. DISCUSSION: The MoVe-ICU
      study will be the first randomized controlled trial to test the hypothesis that
      early rehabilitation with a passive cycle ergometer can preserve the morphology
      of knee extensors and diaphragm in critical patients on MV in ICUs. TRIAL
      REGISTRATION: NCT02300662 (25 November 2014).

PMID- 26314883
TI  - Transcatheter aortic valve implantation in patients with bicuspid aortic valve: a
      series of cases.
AB  - BACKGROUND: Bicuspid aortic valve (BAV) has been considered a relative
      contraindication for transcatheter aortic valve implantation (TAVI). Due to more
      oval shape of the BAV annulus compared to tricuspid aortic valve, the procedure
      has been discouraged because of an increased risk of stent assembly displacement,
      uneven expansion, post-procedure paravalvular leakage, stent valve distortion, or
      other malfunction after implantation. For the same reasons patients with BAV have
      been excluded from the majority of clinical TAVI trials. AIM: To evaluate the
      efficacy and safety of TAVI in patients with BAV stenosis. METHODS: We analysed a
      group of 104 patients admitted to our institution for TAVI between January 2009
      and May 2012. During pre-procedure evaluation, transthoracic and transoesophageal
      (TEE) echocardiography as well as angio-computed tomography (CT) scan were
      performed to assess aortic valve anatomy and morphology. Appropriate measurements
      and detailed analyses of imaging data have been accomplished to select optimal
      access site, prosthesis size as well as to plan the procedure. BAVs were recorded
      in seven patients (6.7%; mean age 77.7 years). These patients presented with
      severe symptomatic aortic valve stenosis with a mean aortic valve area of 0.55
      cm2 (0.46-0.7 cm2) as measured in TEE. All of the patients had been disqualified
      from surgical valve replacement due to high surgical risk with a mean logistic
      Euroscore of 19.9%. All of them successfully underwent TAVI using CoreValve (n =
      5) or Sapien (n = 2) valves. Follow-up was completed at 30 days, and six and 12
      months after the procedure. RESULTS: During follow-up one patient developed an
      elliptic distortion of the aortic prosthesis in CT, although it did not result in
      significant malfunctioning of the implant. One patient died of infective
      endocarditis 30 days after the procedure. Survivors at 30-day follow-up had mild
      to moderate aortic insufficiency, and it did not deteriorate after six months. At
      one year follow-up six out of seven patients remained alive. They achieved
      significant functional improvement by New York Heart Association class compared
      to baseline. CONCLUSIONS: TAVI may constitute an alternative treatment option for
      high-risk patients with BAV, resulting in a low periprocedural mortality rate,
      and good 30-day, six-month, and one-year outcomes.

PMID- 26314882
TI  - Emerging roles of microRNAs in pancreatic cancer diagnosis, therapy and prognosis
      (Review).
AB  - Pancreatic cancer is one of the leading causes of cancer related death.
      Increasing incidence and mortality indicates a lack of detection and post
      diagnostic management of this disease. Recent evidences suggest that, miRNAs are
      very attractive target molecules that can serve as biomarkers for predicting
      development and progression of pancreatic cancer. Furthermore, miRNAs are also
      promising therapeutic targets for pancreatic cancer. The objective of the present
      review is to discuss the significance of miRNA in pancreatic cancer development,
      diagnosis, therapy and prognosis. We extracted and compiled the useful
      information from PubMed database, which satisfied our criteria for analysis of
      miRNAs in pancreatic cancer diagnosis, therapy and prognosis. A summary of the
      most important miRNAs known to regulate pancreatic tumorigenesis is provided. The
      review also provides a collection of evidence that show miRNA profiles of
      biofluids hold much promise for use as biomarkers to predict and detect
      development of pancreatic cancer in its early stages. Identification of key miRNA
      networks in pancreatic cancer will provide long-awaited
      diagnostic/therapeutic/prognostic tools for early detection, better treatment
      options, and extended life expectancy and quality of life in PDAC patients. 

PMID- 26314884
TI  - Exogenous Parathyroid Hormone-Related Peptide Promotes Fracture Healing in Lepr(
      /-) Mice.
AB  - Diabetic osteoporosis continues to surge worldwide, increasing the risk of
      fracture. We have previously demonstrated that haploinsufficiency of endogenous
      parathyroid hormone-related peptide (PTHrP) impairs fracture healing. However,
      whether an exogenous supply of PTHrP can repair bone damage and accelerate
      fracture healing remains unclear. This study aimed to assess the efficacy and
      safety of PTHrP in healing fractures. Standardized mid-diaphyseal femur fractures
      were generated in 12-week-old wild-type and leptin receptor null Lepr(-/-) mice.
      After administration of PTHrP for 2 weeks, callus tissue properties were analyzed
      by radiography, micro-computed tomography, histology, histochemistry,
      immunohistochemistry, and molecular biology techniques. At 2 weeks post-fracture,
      cartilaginous callus areas were reduced, while total callus and bony callus areas
      were increased in PTHrP-treated Lepr(-/-) animals and control wild-type mice,
      compared with vehicle-treated Lepr(-/-) mice. The following parameters were
      enhanced both in Lepr(-/-) mice after treatment with PTHrP and vehicle-treated
      wild-type animals, compared with vehicle-treated Lepr(-/-) mice: osteoblast
      numbers; tissue alkaline phosphatase (ALP) and Type I collagen immunopositive
      areas; mRNA levels of ALP, Type I collagen, osteoprotegerin, and receptor
      activator for nuclear factor-kappa B ligand; protein levels of Runt-related
      transcription factor 2 and insulin-like growth factor-1; and the number and
      surface of osteoclasts. In conclusion, exogenous PTHrP by subcutaneous injection
      promotes fracture repair in Lepr(-/-) mice by increasing callus formation and
      accelerating cell transformation: upregulated osteoblastic gene and protein
      expression, increased endochondral bone formation, osteoblastic bone formation,
      and osteoclastic bone resorption. However, complete repair was not obtained in
      PTHrP-treated Lepr(-/-) mice as in control wild-type animals.

PMID- 26314885
TI  - A clone-free, single molecule map of the domestic cow (Bos taurus) genome.
AB  - BACKGROUND: The cattle (Bos taurus) genome was originally selected for sequencing
      due to its economic importance and unique biology as a model organism for
      understanding other ruminants, or mammals. Currently, there are two cattle genome
      sequence assemblies (UMD3.1 and Btau4.6) from groups using dissimilar assembly
      algorithms, which were complemented by genetic and physical map resources.
      However, past comparisons between these assemblies revealed substantial
      differences. Consequently, such discordances have engendered ambiguities when
      using reference sequence data, impacting genomic studies in cattle and motivating
      construction of a new optical map resource--BtOM1.0--to guide comparisons and
      improvements to the current sequence builds. Accordingly, our comprehensive
      comparisons of BtOM1.0 against the UMD3.1 and Btau4.6 sequence builds tabulate
      large-to-immediate scale discordances requiring mediation. RESULTS: The optical
      map, BtOM1.0, spanning the B. taurus genome (Hereford breed, L1 Dominette 01449)
      was assembled from an optical map dataset consisting of 2,973,315 (439 X; raw
      dataset size before assembly) single molecule optical maps (Rmaps; 1 Rmap = 1
      restriction mapped DNA molecule) generated by the Optical Mapping System. The
      BamHI map spans 2,575.30 Mb and comprises 78 optical contigs assembled by a
      combination of iterative (using the reference sequence: UMD3.1) and de novo
      assembly techniques. BtOM1.0 is a high-resolution physical map featuring an
      average restriction fragment size of 8.91 Kb. Comparisons of BtOM1.0 vs. UMD3.1,
      or Btau4.6, revealed that Btau4.6 presented far more discordances (7,463) vs.
      UMD3.1 (4,754). Overall, we found that Btau4.6 presented almost double the number
      of discordances than UMD3.1 across most of the 6 categories of sequence vs. map
      discrepancies, which are: COMPLEX (misassembly), DELs (extraneous sequences),
      INSs (missing sequences), ITs (Inverted/Translocated sequences), ECs (extra
      restriction cuts) and MCs (missing restriction cuts). CONCLUSION: Alignments of
      UMD3.1 and Btau4.6 to BtOM1.0 reveal discordances commensurate with previous
      reports, and affirm the NCBI's current designation of UMD3.1 sequence assembly as
      the "reference assembly" and the Btau4.6 as the "alternate assembly." The cattle
      genome optical map, BtOM1.0, when used as a comprehensive and largely independent
      guide, will greatly assist improvements to existing sequence builds, and later
      serve as an accurate physical scaffold for studies concerning the comparative
      genomics of cattle breeds.

PMID- 26314887
TI  - Do law students stand apart from other university students in their quest for
      mental health: A comparative study on wellbeing and associated behaviours in law
      and psychology students.
AB  - We are not producing a product, but a well-balanced person.(1) It is well
      documented that law students experience higher levels of psychological distress
      than members of the general population and university students in other
      professional disciplines. In 2014, we published our findings on an empirical
      study identifying the correlations between law student wellbeing and student
      behaviour both at and away from law school. The results of the study informed the
      development of an evidence-based 'behavioural toolkit' to assist law students and
      law schools in making informed choices and decisions that promote and even
      improve the mental health of students. The study we undertook was not, however,
      limited to law students. It extended to collecting quantitative data on
      psychological distress and associated behaviours in psychology students. This
      article reports on the comparative findings of the study and provides a
      comparative basis for understanding the contextual influences on the wellbeing of
      law students. 

PMID- 26314888
TI  - Defendant mental illness and juror decision-making: A comparison of sample types.
AB  - Two studies were conducted with separate student and community samples to explore
      the effect of sample types and the influence of defendant mental illness on juror
      decision-making. Following the completion of a pre-trial questionnaire in which
      jurors' attitudes towards mental illness were assessed, participants were
      provided with a robbery trial transcript, wherein the mental illness of the
      defendant was manipulated. Participants then answered a questionnaire to assess
      their knowledge of the scenario, their verdict, verdict confidence, and
      sentencing decision. Limited relationships were found between the variables in
      both Study 1 and Study 2. Neither attitude ratings nor mental illness type had a
      significant effect on juror decisions. Samples differed in terms of the paths
      through which juror decisions were achieved. Findings suggest that sample type
      may be particularly relevant for this topic of study, and that future research is
      required on legal proceedings for cases involving a defendant with a mental
      illness. 

PMID- 26314889
TI  - Police use of handcuffs in the homeless population leads to long-term negative
      attitudes within this group.
AB  - The police interact with homeless individuals frequently. However, there has been
      relatively little research on the attitudes of homeless individuals towards the
      police, and how police interactions may impact these. This is important since the
      attitudes of homeless individuals can impact how often they report crimes, and
      how well they support police when they are investigating crimes in this
      population. We interviewed 213 homeless individuals in a single city,
      representing approximately 10% of the total homeless population. They were
      interviewed at either homeless shelters, or events held specifically for the
      homeless population. Of these individuals, 75% were male, and 47% had interacted
      with a police officer within the past month. Self-reports suggested that 60% had
      a drug and/or alcohol issue and 78% had a mental illness. We found a highly
      statistically significant difference between the group that had been handcuffed
      and/or arrested compared to those that had not. This was across multiple domains
      and included how the individual regarded the police in terms of their empathy and
      communication skills, and how much they trusted the police. These changes were
      long-term, and if a homeless individual had been arrested or handcuffed (and
      verbal reporting suggested that being handcuffed was the by far the most
      important factor) then these negative attitudes lasted at least 2 years. The
      primary conclusion from this study is that when police handcuff a homeless
      individual, this can lead to long-term negative views about the police across
      several domains that appear to be long lasting, and were linked to feelings of
      not being respected by the police. It is therefore proposed that police officers
      should be made aware of the potential long-term negative consequences of this
      single action, and that police forces should consider providing specific training
      to minimize any unnecessary overuse of handcuffs.

PMID- 26314886
TI  - Genetic determinants of anti-malarial acquired immunity in a large multi-centre
      study.
AB  - BACKGROUND: Many studies report associations between human genetic factors and
      immunity to malaria but few have been reliably replicated. These studies are
      usually country-specific, use small sample sizes and are not directly comparable
      due to differences in methodologies. This study brings together samples and data
      collected from multiple sites across Africa and Asia to use standardized methods
      to look for consistent genetic effects on anti-malarial antibody levels. METHODS:
      Sera, DNA samples and clinical data were collected from 13,299 individuals from
      ten sites in Senegal, Mali, Burkina Faso, Sudan, Kenya, Tanzania, and Sri Lanka
      using standardized methods. DNA was extracted and typed for 202 Single Nucleotide
      Polymorphisms with known associations to malaria or antibody production, and
      antibody levels to four clinical grade malarial antigens [AMA1, MSP1, MSP2, and
      (NANP)4] plus total IgE were measured by ELISA techniques. Regression models were
      used to investigate the associations of clinical and genetic factors with
      antibody levels. RESULTS: Malaria infection increased levels of antibodies to
      malaria antigens and, as expected, stable predictors of anti-malarial antibody
      levels included age, seasonality, location, and ethnicity. Correlations between
      antibodies to blood-stage antigens AMA1, MSP1 and MSP2 were higher between
      themselves than with antibodies to the (NANP)4 epitope of the pre-erythrocytic
      circumsporozoite protein, while there was little or no correlation with total IgE
      levels. Individuals with sickle cell trait had significantly lower antibody
      levels to all blood-stage antigens, and recessive homozygotes for CD36 (rs321198)
      had significantly lower anti-malarial antibody levels to MSP2. CONCLUSION:
      Although the most significant finding with a consistent effect across sites was
      for sickle cell trait, its effect is likely to be via reducing a microscopically
      positive parasitaemia rather than directly on antibody levels. However, this
      study does demonstrate a framework for the feasibility of combining data from
      sites with heterogeneous malaria transmission levels across Africa and Asia with
      which to explore genetic effects on anti-malarial immunity.

PMID- 26314890
TI  - A descriptive evaluation of the Seattle Police Department's crisis response team
      officer/mental health professional partnership pilot program.
AB  - The Seattle Police Department (SPD) recently enhanced their response to
      individuals in behavioral crisis through a pilot Crisis Response Team (CRT)
      consisting of dedicated Crisis Intervention Team (CIT) officers (OFC) paired with
      a Mental Health Professional (MHP). This study presents results of an incident
      based descriptive evaluation of the SPD's CRT pilot program, implemented from
      2010 to 2012. The purpose of the evaluation was to determine the value-added by
      the MHP in cases involving individuals in behavioral crisis as well as the
      effectiveness of the CRT program with regard to resolution time, repeat contacts,
      and referral to services. Data were collected from SPD general offense and
      supplemental reports for a 12-month segment of the program. Key variables
      included incident location, case clearance, repeat contacts, linkages to
      services, and case disposition. Results of analyses of general offense and
      supplemental reports are presented and implications for future development of the
      OFC/MHP partnership are discussed. 

PMID- 26314891
TI  - Trait psychopathy, emotional intelligence, and criminal thinking: Predicting
      illegal behavior among college students.
AB  - Research focusing on individuals high on trait psychopathy remains limited.
      Higher trait psychopathy is associated with lower levels of emotional
      intelligence and increased participation in illegal behavior. Additionally,
      research has confirmed significantly higher levels of criminal thinking and lower
      levels of empathy in the incarcerated psychopathic population. However, the
      relationships between trait psychopathy and criminal thinking have not been
      researched in the community or college population. To test for such differences,
      questionnaires containing relevant measures were administered to 111 college
      students. Results indicated that higher levels of trait psychopathy were
      significantly related to less caring for others, intrapersonal understanding, and
      general mood, and greater interpersonal functioning and stress management.
      Furthermore, trait psychopathy was a strong predictor of violent, property, drug,
      and status offenses. Power-oriented criminal thinking was also predictive of
      violent behaviors, and entitlement predicted property offending. Results suggest
      emotional intelligence is important for predicting psychopathy, and trait
      psychopathy is a strong predictor of all types of illegal behaviors among the non
      incarcerated population. 

PMID- 26314893
TI  - HLA-B27 subtypes in enthesitis-related arthritis category of juvenile idiopathic
      arthritis and ankylosing spondylitis in northern India.
AB  - OBJECTIVES: Enthesitis-related arthritis (ERA) is the most common form of
      juvenile idiopathic arthritis (JIA) in the Asian and Indian populations. The
      presence of HLA-B27 has a strong association with JIA-ERA similar to that with
      adult ankylosing spondylitis (AS). The HLA-B27gene is highly polymorphic.
      Susceptibility to AS varies between different HLA-B27 subtypes; data on the
      relationship of susceptibility to JIA-ERA with HLA-B27 types are scant. In this
      study, we determined HLA-B27 subtypes in patients with JIA-ERA and AS to find out
      whether there is any difference in the HLA-B27 subtypes prevalent in these two
      diseases. METHODS: Genomic DNA from 135 patients with JIA-ERA and 121 with AS was
      tested for the presence of HLA-B27. In patients testing positive, HLA
      B27subtyping was done by sequencing a genomic region that contained second and
      third exons and the intervening intron of this gene; this method permitted
      identification of common HLA-B27 subtypes (HLA-B*27:01 to HLA-B*27:09). RESULTS:
      One hundred and seven (79%) patients with JIA-ERA and 102 (84%) patients with AS
      tested positive for HLA-B27. In both groups, HLA-B*27:05 and HLA-B*27:04 were the
      common subtypes; some patients had HLA-B*27:07(7.4%) and HLA-B*27:18. Patients
      with JIA-ERA had a higher frequency of HLA-B*27:05 than those with AS (70% vs.
      57%, p=0.047), and a lower frequency of HLA-B*27:04 (21% vs. 36%, p=0.018).
      CONCLUSIONS: HLA-B*27:05 and HLA-B*27:04 were the most common HLA-27 subtypes in
      both JIA-ERA and AS. However, HLA-B*27:05 was more frequent and HLA-B*27:04 was
      less frequent in JIA-ERA. It is possible that HLA-B*27:05 being the ancestral HLA
      27 subtype leads to expression of disease early in life.

PMID- 26314892
TI  - Incomplete Dll4/Notch signaling inhibition promotes functional angiogenesis
      supporting the growth of skin papillomas.
AB  - BACKGROUND: In invasive malignancies, Dll4/Notch signaling inhibition enhances
      non-functional vessel proliferation and limits tumor growth by reducing its blood
      perfusion. METHODS: To assess the effects of targeted Dll4 allelic deletion in
      the incipient stages of tumor pathogenesis, we chemically induced skin papillomas
      in wild-type and Dll4 (+/-) littermates, and compared tumor growth, their
      histological features, vascularization and the expression of angiogenesis-related
      molecules. RESULTS: We observed that Dll4 down-regulation promotes productive
      angiogenesis, although with less mature vessels, in chemically-induced pre
      cancerous skin papillomas stimulating their growth. The increase in endothelial
      activation was associated with an increase in the VEGFR2 to VEGFR1 ratio, which
      neutralized the tumor-suppressive effect of VEGFR-targeting sorafenib. Thus, in
      early papillomas, lower levels of Dll4 increase vascularization through raised
      VEGFR2 levels, enhancing sensitivity to endogenous levels of VEGF, promoting
      functional angiogenesis and tumor growth. CONCLUSION: Tumor promoting effect of
      low-dosage inhibition needs to be considered when implementing Dll4 targeting
      therapies.

PMID- 26314894
TI  - Behavioral and biochemical effects of pharmacopuncture (ST 36 and ST 25) in obese
      rats.
AB  - BACKGROUND: Acupuncture has been reported as a weight loss treatment for obese
      patients. The use of pharmacopuncture focusing on behavioral analyses has not yet
      been studied with the objective of treating obesity. Thus, this study aimed to
      assess the biochemical and behavioral effects of using pharmacopuncture
      techniques in obese Wistar rats. METHODS: The treatments consisted in applying
      pharmacopuncture at the Zusanli (ST 36) and Tianshu (ST 25) points. RESULTS: When
      treated with pharmacopuncture, groups HDP36 and HDP25 experienced a reduction in
      body weight compared to the controls, who were also fed a hypercaloric diet. In
      the alimentary behavior test, latency to feed did not differ between the groups.
      However, groups HDP36 and HDP25 consumed a smaller number of cereals bits, which
      suggests that inappetence was an effect of the treatment. No difference was found
      among the groups in the elevated plus maze test, which indicates no anxiety
      action of the points studied. Regarding post mortem perirenal and abdominal fat
      among the groups fed a hypercaloric diet, groups HDP36 and HDP25 had lower
      perirenal fat weight and HDP36 had lower abdominal fat weight compared to the
      other groups. Likewise, a reduction in cholesterol 10.1186/s12906-015-0829-7 and
      glucose levels was found in groups HDP36 and HDP25 compared to the other groups
      that were fed a hypercaloric diet, while triglycerides decreased in subgroup
      HDP25 CONCLUSIONS: In conclusion, the present study showed the efficacy of
      pharmacopuncture in weight loss of obese rats, as well as changes in biochemical
      and behavioral parameters.

PMID- 26314895
TI  - Pearls and pitfalls in surgery for endometrioma.
AB  - Endometrioma surgery should be planned and executed very carefully as it is
      associated with risks that may hamper future reproductive potential. Symptoms,
      age, risk of malignancy, bilaterality, ovarian reserve, and desire to have
      children should all be taken into account prior to surgical intervention. Cyclic
      and noncyclic severe pain may be an indicator or deep infiltrating diseases.
      Laparoscopic surgery is the gold standard, however, the issue of resection versus
      ablation should be further studied. 

PMID- 26314896
TI  - Bis(alkyl) rare-earth complexes supported by a new tridentate amidinate ligand
      with a pendant diphenylphosphine oxide group. Synthesis, structures and catalytic
      activity in isoprene polymerization.
AB  - A new tridentate amidine 2-[Ph2P(O)]C6H4NHC(tBu)[double bond, length as m
      dash]N(2,6-Me2C6H3) (1) bearing a side chain pendant Ph2P[double bond, length as
      m-dash]O group was synthesized and proved to be a suitable ligand for
      coordination to rare-earths ions. Bis(alkyl) complexes {2
      [Ph2P(O)]C6H4NC(tBu)N(2,6-Me2C6H3)}Ln(CH2SiMe3)2(THF)n (Ln = Y, n = 1 (3), Ln =
      Er, n = 1 (4), Ln = Lu, n = 0 (5)) were prepared using alkane elimination
      reactions of and Ln(CH2SiMe3)3(THF)2 (Ln = Y, Er, Lu) in hexane and were isolated
      in 50, 70 and 75% yields respectively. The X-ray studies revealed that complexes
      2-5 feature intramolecular coordination of P[double bond, length as m-dash]O
      groups to metal ions. The lutetium complex 5 proved to be rather stable: at 20 
      degrees C its half-life time is 1155 h, while for the yttrium analogue the half
      life time was found to be 63 h. Complexes 3-5 were evaluated as precatalysts for
      isoprene polymerization. The systems Ln/borate/AliBu3 (Ln = 3-5, borate =
      [PhNHMe2][B(C6F5)4], [Ph3C][B(C6F5)4]) turned out to be highly efficient in
      isoprene polymerization and enable complete conversion of 1000-10,000 equivalents
      of monomer into polymer at 20  degrees C within 0.5-2.5 h affording polyisoprenes
      with a very high content of 1,4-cis units (up to 96.6%) and from narrow (1.49) to
      moderate (3.54) polydispersities. A comparative study of catalytic performance of
      the related bis(alkyl) yttrium complexes supported by amidinate ligands of
      different denticities and structures [tBuC(N-2,6iPr2C6H4)2](-), [tBuC(N-2,6
      iPr2C6H4)(N-2-MeOC6H4)](-) and {2-[Ph2P(O)]C6H4NC(tBu)N(2,6-Me2C6H3)}(-)
      demonstrated that the introduction of a pendant donor group (2-MeOC6H4 or
      Ph2P(O)) into a side chain of amidinate scaffolds results in a significant
      increase in catalytic activity. The amidinate ligand bearing a Ph2P(O)-group
      provides a high isoprene polymerization rate along with excellent control over
      regio- and stereoselectivities and allows us to obtain polyisoprenes with a
      reasonable molecular weight distribution.

PMID- 26314897
TI  - [Treatment of age-related macular degeneration: Expert opinion and therapeutic
      algorithm].
AB  - Intravitreal injections (IVT) of aflibercept are indicated in France for the
      treatment of neovascular age-related macular degeneration (AMD). An induction
      phase consisting of 3 monthly IVTs followed by follow-up visits and IVTs every
      other month during the first year is recommended. However, it may be necessary to
      adjust this schedule for some patients who might benefit from a more tailored
      approach, namely a follow-up visit immediately after the induction phase. The
      goal was to develop a treatment algorithm that would reflect current clinical
      experience and the opinions of experts on neovascular AMD. METHODS: A group of
      retinologists took positions on therapeutic questions regarding management of AMD
      using a nominal group technique (NGT). The results were combined to create a
      treatment algorithm. RESULTS: Seventy-nine percent of experts considered that the
      approved schedule was efficacious when fluid was completely resorbed after the
      induction phase. Ninety-four percent of experts recommended, after a successful
      induction phase, a monthly follow-up visit for 3 to 6 months in order to
      determine the rhythm of recurrence for each patient. Ninety-six percent of
      experts recommended that persistent fluid after the induction phase, even if
      visual acuity is improved satisfactorily, should be a criterion for systematic
      retreatment. CONCLUSION: The proposed algorithm (expert opinion) after the first
      year of use of aflibercept in France captures the complexity of the clinical
      cases that exist in daily practice and the necessity for regular follow-ups.

PMID- 26314898
TI  - Ocular adnexal marginal zone B cell lymphoma presenting with orbital apex
      syndrome.

PMID- 26314900
TI  - Laser induced alignment of state-selected CH3I.
AB  - Hexapole state selection is used to prepare CH3I molecules in the |JKM> = |1+/
      1?1> state. The molecules are aligned in a strong 800 nm laser field, which is
      linearly polarised perpendicular to the weak static extraction field E of the
      time of flight setup. The molecules are subsequently ionised by a second time
      delayed probe laser pulse. It will be shown that in this geometry at high enough
      laser intensities the Newton sphere has sufficient symmetry to apply the inverse
      Abel transformation to reconstruct the three dimensional distribution from the
      projected ion image. The laser induced controllable alignment was found to have
      the upper and lower extreme values of <P2(cos theta)> = 0.7 for the aligned
      molecule and -0.1 for the anti-aligned molecule, coupled to <P4(cos theta)>
      between 0.3 and 0.0. The method to extract the alignment parameters <P2(cos
      theta)> and <P4(cos theta)> directly from the velocity map ion images will be
      discussed. 

PMID- 26314899
TI  - Dissecting the role of distinct OCT4-SOX2 heterodimer configurations in
      pluripotency.
AB  - The transcription factors OCT4 and SOX2 are required for generating induced
      pluripotent stem cells (iPSCs) and for maintaining embryonic stem cells (ESCs).
      OCT4 and SOX2 associate and bind to DNA in different configurations depending on
      the arrangement of their individual DNA binding elements. Here we have
      investigated the role of the different OCT4-SOX2-DNA assemblies in regulating and
      inducing pluripotency. To this end, we have generated SOX2 mutants that interfere
      with specific OCT4-SOX2 heterodimer configurations and assessed their ability to
      generate iPSCs and to rescue ESC self-renewal. Our results demonstrate that the
      OCT4-SOX2 configuration that dimerizes on a Hoxb1-like composite, a canonical
      element with juxtaposed individual binding sites, plays a more critical role in
      the induction and maintenance of pluripotency than any other OCT4-SOX2
      configuration. Overall, the results of this study provide new insight into the
      protein interactions required to establish a de novo pluripotent network and to
      maintain a true pluripotent cell fate. 

PMID- 26314901
TI  - [Rapidly progressive dementia in an 81 year-old man].

PMID- 26314902
TI  - Effect of gabapentin pretreatment on the hemodynamic response to laryngoscopy and
      tracheal intubation in treated hypertensive patients.
AB  - OBJECTIVE: This randomized, double-blind study was conducted to evaluate the
      effect of gabapentin pretreatment on the hemodynamic response to laryngoscopy and
      endotracheal intubation (LETI) in treated hypertensive patients undergoing
      surgery. METHODS: A total of 100 controlled hypertensive patients aged 35-60
      years, undergoing elective surgery under general anesthesia with endotracheal
      intubation, were randomly allocated into three groups. Group 1 patients received
      placebo at night and 2 hours prior to induction of anesthesia. Group 2 patients
      received placebo at night and 800 mg gabapentin 2 hours prior to induction of
      anesthesia. Group 3 patients received 800 mg gabapentin at night and 2 hours
      prior to induction of anesthesia. Anesthesia was induced with thiopentone,
      fentanyl, and vecuronium and maintained with isoflurane in oxygen and nitrous
      oxide. Patients' heart rate (HR), blood pressure (BP), and electrocardiography
      (ECG) changes were recorded prior to induction, after induction, and at 0
      minutes, 1 minute, 3 minutes, 5 minutes, and 10 minutes after intubation. Any
      episodes of hypotension, bradycardia, tachycardia, hypertension, arrhythmia, and
      ST-T wave changes were recorded and treated accordingly. RESULTS: The HR was
      comparable among groups, with a transient rise just after intubation, followed by
      a gradual fall thereafter at 3 minutes, 5 minutes, and 10 minutes compared with
      baseline. A significant increase in BP after intubation was reported in Group 1
      but not in Group 2 and Group 3. The mean arterial pressure (MAP) was
      significantly higher in Group 1 at 0 minute, 1 minute and 3 minutes
      postintubation as compared with Group 2 and Group 3 (p=0.014). Three patients in
      Group 1, four patients in Group 2, and 10 patients in Group 3 developed
      hypotension and were treated with ephedrine, whereas five patients in Group 1 and
      one patient in Group 2 had hypertension after tracheal intubation. There was no
      significant difference between the groups with respect to the number of patients
      who received ephedrine boluses and in whom isoflurane had to be increased due to
      hypertension. No episode of bradycardia, tachycardia, dysrhythmia, or ST-T wave
      changes was reported. CONCLUSION: Gabapentin 800 mg in a single or double dose
      was equally effective in attenuating the hypertensive response to laryngoscopy
      and tracheal intubation in treated hypertensive patients.

PMID- 26314903
TI  - Rational and precise development of amorphous polymeric systems with dapsone by
      response surface methodology.
AB  - This work aimed to design dapsone (DAP) amorphous Polymeric Dispersions (PD)
      using design of experiments (DoE) and response surface methodology (RSM) as
      optimization tools in order to tailor the biopharmaceutical properties toward its
      oral delivery. A two-factor, three-level (3(2)) statistical design was
      implemented to study the influence of input variables (amount of PVP K30 and
      Pluronic F68) on the equilibrium solubility of DAP of the physical mixture (PM),
      kneaded (KN) and freeze dried (FD) PDs. Through the analysis, it was found that
      equilibrium solubility of DAP was improved with increasing of PVP K30, mainly for
      FD PDs, but decreased with increasing Pluronic F68 concentration. XRD and FTIR
      spectrum revealed the amorphous characteristic of FD PDs and SEM confirmed the
      homogeneity of the system leading to enhanced surface area and consequent
      dissolution rate. The in vitro dissolution rate of PDs was significantly faster
      compared to DAP and PM, and all the similarity factors (f2) were below 50,
      demonstrating the differences on the dissolution profiles. The results
      established the effectiveness of PDs for improvement of dissolution and
      solubility of DAP and the success in the implementation of DoE and RSM as QbD
      tools in the design of PDs. 

PMID- 26314904
TI  - A polysaccharide from cultured mycelium of Hericium erinaceus and its anti
      chronic atrophic gastritis activity.
AB  - A polysaccharide named EP-1 was found by screening cultured mycelium of Hericium
      erinaceus, which was extracted and subjected to precipitation with ethanol,
      hollow-fiber ultrafiltration and ion-exchange chromatography. The polysaccharide
      has a molecular weight of approximately 3100Da and is composed of glucose,
      mannose and galactose, thus being a heteroglycan. EP-1 has a backbone of alpha-d
      Glc(1->3) and beta-d-Glc(1->3). The beta-d-Glc(1->3) and alpha-d-Gal-(1->3) were
      regarded as branches attached to the C-4 position. The alpha-d-Man was regarded
      as a terminal residue. The anti-CAG activity was evaluated in experimental
      systems using a cell model for identification. The polysaccharide significantly
      inhibited the growth of MC cells obtained from human gastric mucosa epithelium
      (GES-1) cells transformed by MNNG, which were used as a chronic atrophic
      gastritis cell model. It also interfered with the MC cells by inducing cell cycle
      arrest. Thus, EP-1 shows potential for the development of new functional foods
      and drugs. 

PMID- 26314905
TI  - Overexpression of PDZ-binding kinase confers malignant phenotype in prostate
      cancer via the regulation of E2F1.
AB  - Roles and mechanisms of cell cycle-specific transcription factor E2F1 on prostate
      cancer (PCa) have not been fully elucidated. To address this problem, we here
      identified PDZ-binding kinase (PBK) as a direct target for E2F1 through
      bioinformatics binding site prediction, combined with chromatin
      immunoprecipitation-PCR (ChIP-PCR), quantitative (Q)-PCR and Western blot
      analysis. Then, we observed that the knockdown of both E2F1 and PBK could
      suppress cell proliferation, invasion and migration of PCa cell lines in vitro.
      Based on Taylor dataset, we found that PBK upregulation occurred more frequently
      in PCa patients with the older age of patients (P=0.044), the higher Gleason
      score (P<0.001), the advanced clinical pathological stage (P=0.019), the presence
      of metastasis (P=0.008), the overall survival (P<0.001) and PSA failure
      (P=0.004). More interestingly, the survival analysis identified PBK as an
      independent factor for predicting the biochemical recurrence-free survival of PCa
      patients (P=0.041). Taken together, these findings offer the convincing evidence
      for the first time that the overexpression of PBK may lead to high malignant
      phenotype in PCa cells via the regulation of E2F1. PBK may function as a
      biomarker that can differentiate patients with biochemical recurrent and non
      biochemical recurrent disease following radical prostatectomy, highlighting its
      potential as a therapeutic target. 

PMID- 26314906
TI  - Enhancing mechanical properties of chitosan films via modification with vanillin.
AB  - The vanillin/chitosan composite films were prepared using the solvent evaporation
      method. The properties of the films including optical property, water vapor
      permeability (WVP), tensile strength (TS) and elongation at break (%E) were
      studied to investigate the effect of cross-linking agent of vanillin on chitosan
      films by thermogravimetric analysis (TGA), scanning electron microscopy (SEM), X
      ray diffraction (XRD) and Fourier transform infrared spectrum (FT-IR). Results
      showed that the TS of composite films increased by 53.3% and the WVP decreased by
      36.5% compared with pure chitosan film that were due to the formation of the
      dense network structure by FT-IR spectra. There were almost no changes of the
      thermal stability of the composite films compared with the pure chitosan film by
      TGA analysis. In addition, from the SEM images, it could be seen that the film
      with addition of vanillin with 0.5-10% concentration exhibited good
      compatibility. 

PMID- 26314907
TI  - Surface ion-imprinted amino-functionalized cellulosic cotton fibers for selective
      extraction of Cu(II) ions.
AB  - Surface ion-imprinted amino-functionalized cellulosic fibers (Cu-ABZ) were
      manufactured for efficient selective adsorption of Cu(2+) ions. The chemical
      modification steps had been characterized utilizing elemental analysis; Fourier
      transforms infrared (FTIR) along with wide angle X-ray diffraction (XRD)
      spectroscopy. Also, the morphological structure of the ion-imprinted and the non
      imprinted (NI-ABZ) fibers were visualized and compared with that of the native
      cotton fibers using scanning electron microscope (SEM). In addition, the
      coordination mode by which the Cu(2+) ions bonded to the active sites were
      examined by both FTIR and X-ray photo electron spectra (XPS). Both Cu-ABZ and NI
      ABZ were implemented in batch experiments for optimizing the conditions by which
      the Cu(2+) ions can be selectively removal from aqueous medium and pH 5 was the
      optimum for the metal ion extraction. Moreover, the kinetics and isotherm studies
      revealed that the adsorption data fitted with pseudo-second-order kinetic and
      Langmuir models with estimated maximum adsorption capacity 93.6mg/g. Also, the
      reusability studies indicated that the prepared ion-imprinted adsorbent maintains
      more than 95% of its original activity after fifth generation cycle. 

PMID- 26314908
TI  - Antibacterial performance of bovine lactoferrin-fish gelatine electrospun
      membranes.
AB  - The increase of antibiotic resistant microorganisms urged the development and
      synthesis of novel antimicrobial biomaterials to be employed in a broad range of
      applications, ranging from food packaging to medical devices. This work describes
      the production and characterization of a protein-based electrospun fibrous
      membranes bearing antimicrobial properties. Its composition is exclusively
      comprised of proteins, with fish gelatine as structural matrix and bovine
      lactoferrin (bLF) as the active antimicrobial agent. The bLF bactericidal effect
      was determined against clinical isolates of Escherichia coli and Staphylococcus
      aureus through microdilution assays. Two distinctive methods were used to
      incorporate bLF into the fish gelatine nanofibres: (i) as a filler in the
      electrospinning formulation with concentrations of 2, 5 and 10 (wt%), and cross
      linked with glutaraldehyde vapour, in order to achieve stability in aqueous
      solution; and (ii) through adsorption in a solution with 40mgmL(-1) bLF. Fourier
      transform infrared spectroscopy analysis showed that the structure of both
      proteins remained intact through the electrospinning blending and cross-linking
      procedure. Remarkable antibacterial properties were obtained with membranes
      containing 5% and 10% bLF with a bacterial reduction of approximately 90% and
      100%, respectively. 

PMID- 26314909
TI  - Poly(3-hydroxybutyrate)-ethyl cellulose based bio-composites with novel
      characteristics for infection free wound healing application.
AB  - A series of bio-composites including poly3-hydroxybutyrate [P(3HB)] grafted ethyl
      cellulose (EC) stated as P(3HB)-EC were successfully synthesised. Furthermore,
      natural phenols e.g., p-4-hydroxybenzoic acid (HBA) and ferulic acid (FA) were
      grafted onto the newly developed P(3HB)-EC-based bio-composites under laccase
      assisted environment without the use of additional initiators or crosslinking
      agents. The phenol grafted bio-composites were critically evaluated for their
      antibacterial and biocompatibility features as well as their degradability in
      soil. In particular, the results of the antibacterial evaluation for the newly
      developed bio-composites indicated that 20HBA-g-P(3HB)-EC and 15FA-g-P(3HB)-EC
      bio-composites exerted strong bactericidal and bacteriostatic activity against
      Gram(-)E. coli NTCT 10418 as compared to the Gram(+)B. subtilis NCTC 3610. This
      study shows further that at various phenolic concentrations the newly synthesised
      bio-composites remained cytocompatible with human keratinocyte-like HaCaT skin
      cells, as 100% cell viability was recorded, in vitro. As for the degradation, an
      increase in the degradation rate was recorded during the soil burial analyses
      over a period of 42 days. These findings suggest that the reported bio-composites
      have great potential for use in wound healing; covering the affected skin area
      which may favour tissue repair over shorter periods. 

PMID- 26314910
TI  - Anti-inflammatory potential of probiotic Lactobacillus spp. on carrageenan
      induced paw edema in Wistar rats.
AB  - The aim of the present study was to evaluate the anti-inflammatory ability of
      novel indigenous probiotic Lactobacillus fermentum MCC 2759, L. fermentum MCC
      2760 and Lactobacillus delbrueckii MCC 2775 in a carrageenan induced acute
      inflammatory paw edema model. Probiotic cultures were administered to male Wistar
      rats via oral route. Carrageenan at a concentration of 1% was injected into hind
      paw of rats 30min after oral gavage on the 8th day of treatment regimen. Paw
      thickness (mm), stair climbing activity and motility score were the parameters
      used to score the inflammatory response. L. fermentum MCC 2759, L. fermentum MCC
      2760 and L. delbrueckii MCC 2775 showed significant reduction in paw thickness
      (P<0.05) showing percentage inhibition of 15.67%, 14.72% and 14.84%,
      respectively, 24h after carrageenan induction. Probiotic treatment also markedly
      alleviated the stair climbing and motility score. Histological analysis of tissue
      sections revealed reduction in cellular infiltration of probiotic and drug
      treatment groups. Adhesion to resected rat intestinal tissue also showed
      significant adherence capability (>40%) of the probiotic cultures used.
      Therefore, L. fermentum MCC 2759, L. fermentum MCC 2760 and L. delbrueckii MCC
      2775 may be used as potent anti-inflammatory agents with probiotic health
      benefits. 

PMID- 26314911
TI  - Integration of photonic nanojets and semiconductor nanoparticles for enhanced all
      optical switching.
AB  - All-optical switching is the foundation of emerging all-optical (terabit-per
      second) networks and processors. All-optical switching has attracted considerable
      attention, but it must ultimately support operation with femtojoule switching
      energies and femtosecond switching times to be effective. Here we introduce an
      all-optical switch architecture in the form of a dielectric sphere that focuses a
      high-intensity photonic nanojet into a peripheral coating of semiconductor
      nanoparticles. Milli-scale spheres coated with Si and SiC nanoparticles yield
      switching energies of 200 and 100 fJ with switching times of 10 ps and 350 fs,
      respectively. Micro-scale spheres coated with Si and SiC nanoparticles yield
      switching energies of 1 pJ and 20 fJ with switching times of 2 ps and 270 fs,
      respectively. We show that femtojoule switching energies are enabled by localized
      photoinjection from the photonic nanojets and that femtosecond switching times
      are enabled by localized recombination within the semiconductor nanoparticles.

PMID- 26314912
TI  - Genome-wide identification, classification and expression analysis of the PHD
      finger protein family in Populus trichocarpa.
AB  - The plant homeobox domain (PHD) proteins are widespread in eukaryotes, and play
      important roles in regulating chromatin and transcription. Comprehensive analyses
      of PHD-finger proteins have been performed in animals, but few plant PHD-finger
      proteins involved in growth and development have been characterized functionally.
      In this study, we conducted a genome-wide survey of PHD-finger proteins in
      Populus trichocarpa by describing the phylogenetic relationship, gene structure,
      and chromosomal location and microarray analyses of each predicted PHD-finger
      family member. We identified 73 PHD-finger genes (PtPHD1-73) and classified them
      into eleven subfamilies (A-K) by phylogenetic analysis. Seventy-two of the 73
      genes were unevenly distributed on all 19 chromosomes, with seven segmental
      duplication events. Analysis of the Ka (non-synonymous substitution rate)/Ks
      (synonymous substitution rate) ratios suggested that the duplicated genes of the
      PHD-finger family mainly underwent purifying selection with restrictive
      functional divergence after the duplication events. Expression profiles analysis
      indicated that 67 PHD-finger genes were differentially expressed in various
      tissues. Quantitative real-time RT-PCR (qRT-PCR) analyses of nine selected PtPHD
      genes under high salinity, drought and cold stresses were also performed to
      explore their stress-related expression patterns. The results of this study
      provide a thorough overview of poplar PHD-finger proteins and will be valuable
      for further functional research of poplar PHD-finger genes to unravel their
      biological roles. 

PMID- 26314913
TI  - Dielectric relaxation, resonance and scaling behaviors in Sr3Co2Fe24O41
      hexaferrite.
AB  - The dielectric properties of Z-type hexaferrite Sr3Co2Fe24O41 (SCFO) have been
      investigated as a function of temperature from 153 to 503 K between 1 and 2 GHz.
      The dielectric responses of SCFO are found to be frequency dependent and
      thermally activated. The relaxation-type dielectric behavior is observed to be
      dominating in the low frequency region and resonance-type dielectric behavior is
      found to be dominating above 10(8) Hz. This frequency dependence of dielectric
      behavior is explained by the damped harmonic oscillator model with temperature
      dependent coefficients. The imaginary part of impedance (Z") and modulus (M")
      spectra show that there is a distribution of relaxation times. The scaling
      behaviors of Z" and M" spectra further suggest that the distribution of
      relaxation times is temperature independent at low frequencies. The dielectric
      loss spectra at different temperatures have not shown a scaling behavior above
      10(8) Hz. A comparison between the Z" and the M" spectra indicates that the short
      range charges motion dominates at low temperatures and the long-range charges
      motion dominates at high temperatures. The above results indicate that the
      dielectric dispersion mechanism in SCFO is temperature independent at low
      frequencies and temperature dependent at high frequencies due to the domination
      of resonance behavior. 

PMID- 26314914
TI  - Sample Size Calculations for Detecting Disease-Modifying Osteoarthritis Drug
      Effects on Knee Replacement Incidence in Clinical Trials: Data From the
      Osteoarthritis Initiative.
AB  - OBJECTIVE: To evaluate the extent to which the current designs of clinical trials
      in knee osteoarthritis (OA) permit detection of a therapeutic effect of disease
      modifying OA drugs (DMOADs) on the incidence of knee replacement, and to provide
      estimates of the required sample sizes. METHODS: We selected distinct subcohorts
      of the Osteoarthritis Initiative (OAI), based on available information on
      eligibility criteria for clinical knee OA trials (ClinicalTrials.gov) and
      additional subcohorts stratified for age, sex, and the severity of radiographic
      OA. The observed incidence of knee replacement in these OAI subcohorts was used
      to estimate the expected incidence of knee replacement in the control group of a
      clinical trial. Based on this estimate, the sample sizes required to detect
      hypothetical treatment effects on the incidence of knee replacement were
      calculated, assuming observation periods of 2, 5, or 7 years. RESULTS: The
      cumulative knee replacement incidence rates in the OAI subcohorts ranged from
      0.9% to 12.9%. The corresponding sample sizes required to detect 50% improvement
      by the DMOAD, with a power of 80% and 95% confidence, were 5,459 and 362,
      respectively. Including only women with advanced age and radiographic OA
      increased the incidence of knee replacement and decreased the required sample
      size. CONCLUSION: The sample sizes that are commonly used in clinical trials do
      not enable the effects of a DMOAD on incident knee replacement to be detected
      with sufficient power and confidence. The estimated incidence rates of knee
      replacement and the corresponding sample sizes are important for informing the
      design of trials for disease course-modifying effects as well as for
      socioeconomic evaluation of a DMOAD in terms of preventing knee replacement.

PMID- 26314915
TI  - Emergence of primary drug resistance to rifampicin in Mycobacterium leprae
      strains from leprosy patients in India.

PMID- 26314916
TI  - Streptococcus gallolyticus meningitis in adults: report of five cases and review
      of the literature.
AB  - We describe the incidence and patient characteristics of Streptococcus
      gallolyticus meningitis. We identified S. gallolyticus meningitis in a nationwide
      cohort of patients with community-acquired bacterial meningitis, and performed a
      systematic review and meta-analysis of all reported adult cases in the
      literature. Five cases were identified (0.3%) in a cohort of 1561 episodes of
      bacterial meningitis. In one patient, bowel disease (colon polyps) was identified
      as a predisposing condition for S. gallolyticus infection, whereas no patients
      were diagnosed with endocarditis. In a combined analysis of our patients and 37
      reported in the literature, we found that the median age was 59 years.
      Predisposing factors were present in 21 of 42 patients (50%), and mainly
      consisted of immunosuppressive therapy (seven patients), cancer (four patients),
      and alcoholism (four patients). Colon disease was identified in 15 of 24 patients
      (63%) and endocarditis in five of 27 patients (18%). Co-infection with
      Strongyloides stercoralis was identified in 14 of 34 patients (41%), ten of whom
      were infected with human immunodeficiency virus or human T-lymphotropic virus.
      Outcomes were described for 37 patients; eight died (22%) and one (3%) had
      neurological sequelae. S. gallolyticus is an uncommon cause of bacterial
      meningitis, with specific predisposing conditions. When it is identified,
      consultation with a cardiologist and gastroenterologist is warranted to rule out
      underlying endocarditis or colon disease. Stool examinations for Strongyloides
      stercoralis should be performed in patients who have travelled to or originate
      from endemic areas. 

PMID- 26314917
TI  - Trends in Injection Drug Use Among High School Students, U.S., 1995-2013.
AB  - INTRODUCTION: Injection drug use is the most frequently reported risk behavior
      among new cases of hepatitis C virus infection, and recent reports of increases
      in infection are of great concern in many communities. This study assessed the
      prevalence and trends in injection drug use among U.S. high school students.
      METHODS: Data were from CDC's Youth Risk Behavior Surveillance System, which
      collects information on health risk behaviors at the national, state, and large
      urban school district levels. Analyses were conducted in 2014. RESULTS: In 2013,
      1.7% of high school students nationwide had ever injected any illegal drug.
      Nationwide, ever injecting any illegal drug did not change significantly from
      1995 to 2013, except among black non-Hispanic students. For this subgroup, both a
      significant linear increase from 1995 to 2013 and a significant quadratic trend
      were observed, with injection drug use increasing from 1995 to 2009 and
      decreasing from 2009 to 2013. Significant linear increases in injection drug use
      occurred in five states (Arkansas, Hawaii, Maine, Maryland, and New York) and six
      large urban school districts (Baltimore, Memphis, Miami-Dade County, New York
      City, Philadelphia, and Seattle). Significant linear decreases occurred in three
      states (Massachusetts, South Dakota, and West Virginia). Both a significant
      linear increase and quadratic trend were observed in Maine; quadratic trends were
      observed in Tennessee, Utah, and Palm Beach County, Florida. CONCLUSIONS: In some
      geographic areas and population groups, an increasing or high frequency of
      injection drug use was found among high school students, who should be targeted
      for prevention.

PMID- 26314918
TI  - Modeling strategies to study metabolic pathways in progression to type 1 diabetes
      -Challenges and opportunities.
AB  - Seroconversion to islet autoimmunity is preceded by metabolic disturbances in
      children who later progress to overt type 1 diabetes (T1D). The underlying
      metabolic pathways and the interaction of metabolic and immune system factors
      involved in progression to the disease are however poorly understood. There is a
      clear need for mathematical models which capture the temporal and spatial
      complexity of early pathogenesis of T1D. Here we review the early attempts to
      model the development of islet autoimmunity and T1D, including the models which
      emphasize the potential beneficial role of autoimmune response in specific
      circumstances, such as to 'correct' for the early metabolic disturbances. We also
      highlight the genome-scale metabolic modeling as a promising new avenue to study
      metabolism and its interactions with the immune system in T1D. 

PMID- 26314919
TI  - Strategic development of medicines information: Expanding key global initiatives.
AB  - Medicines information (MI) is a broad concept that includes information targeted
      to health care professionals as well as to patients. It may be in written,
      electronic or verbal forms. The internet is becoming more widely used as a source
      for MI, even though research shows that health care professionals and patient
      information leaflets are still the most common sources for medicine users. As
      patients are increasingly looking for the information they need themselves, the
      role of health care professionals in providing information is evolving, and there
      exists a need for greater health literacy skills among the patients. Medicines
      information as a concept is often defined and understood differently.
      Furthermore, it is such an integral part of pharmacy practice that it is rarely
      discussed as a separate entity. However, there is a growing recognition of a need
      to discuss MI in a broader sense and consider national strategies to meet
      consumer needs for medicines information. It also has been recognized that
      provision of MI should be a shared responsibility of all stakeholders in health
      care. This commentary gives an example of national level strategic development of
      MI, and calls for international collaboration.

PMID- 26314920
TI  - A model to inform community pharmacy's collaboration in outpatient care.
AB  - Value-driven health care and team-based care are gaining momentum from
      policymakers, payers, and providers. An important facet to examine is the health
      care team, especially in outpatient care. Community pharmacy is a significant
      aspect of the patient's health experience and a valuable component of outpatient
      care. An in-depth look into how community pharmacy can participate in the
      outpatient care team is described. To function as a team, it is crucial to
      address collaboration among outpatient practices, while making it easier for
      patients to navigate the outpatient health system. Previously published
      characteristics, principles, and values of effective health care teams within
      primary care can aid in establishing teams across practice settings including
      community pharmacy.

PMID- 26314921
TI  - In wealthier countries, patients perceive worse impact of the disease although
      they have lower objectively assessed disease activity: results from the cross
      sectional COMORA study.
AB  - OBJECTIVES: To investigate patterns in patient-reported and physician-reported
      disease outcomes in patients with rheumatoid arthritis (RA) from countries with
      different level of socioeconomic development. METHODS: Data from a cross
      sectional multinational study (COMOrbidities in RA) were used. Contribution of
      socioeconomic welfare (gross domestic product (GDP); low vs high) of country of
      residence to physician-reported (tender joint count, swollen joint count (SJC),
      erythrocyte sedimentation rate, disease activity score based on 28 joints
      assessment (DAS28)-3v based on these three components and physician global
      assessment) and patient-reported (modified Health Assessment Questionnaire
      (mHAQ), patient global assessment and fatigue) disease outcomes was explored in
      linear regressions, adjusting for relevant confounders. RESULTS: In total, 3920
      patients with RA from 17 countries (30 to 411 patients per country) were
      included, with mean age of 56 years (SD13) and 82% women. Mean SJC varied between
      6.7 (Morocco) and 0.9 (The Netherlands), mean mHAQ ranged between 0.7 (Taiwan)
      and 1.5 (The Netherlands). Venezuela had the lowest (1.7) and the Netherlands the
      highest score on fatigue (5.0). In fully adjusted models, lower GDP was
      associated with worse physician-reported outcomes (1.85 and 2.84 more swollen and
      tender joints, respectively, and 1.0 point higher DAS28-3v), but only slightly
      worse performance-based patient-reported outcome (0.15 higher mHAQ), and with
      better evaluation-based patient-reported outcomes (0.43 and 0.97 points lower on
      patient global assessment and fatigue, respectively). CONCLUSIONS: In patients
      with RA, important differences in physician-reported and patient-reported
      outcomes across countries were seen, with overall a paradox of worse physician
      reported outcomes but better patient-reported outcomes in low-income countries,
      while results indicate that these outcomes in multinational studies should be
      interpreted with caution. Research on explanatory factors of this paradox should
      include non-disease driven cultural factors influencing health.

PMID- 26314922
TI  - Imidazopyridines as a source of biological activity and their pharmacological
      potentials-Infrared and Raman spectroscopic evidence of their content in
      pharmaceuticals and plant materials.
AB  - Derivatives of imidazopyridine are used in medicinal chemistry due to their
      biological and pharmaceutical properties. This review article presents
      imidazopyridine pharmacological activity as antiinflammatory, anticancer,
      antiviral, antiosteoporotic, antiparasitic, and antihypertensive agents by
      studying its various synthesized derivatives. Some of compounds with
      imidazopyridine skeleton are used in psychiatry and autoimmune disorders. The
      presented data suggest that IR and Raman spectra measurements are a good methods
      for identification and characterization of the compounds containing
      imidazopyridine core. Two stretching vibrations: nuas(Phi) and nus(Phi) are of a
      diagnostic importance. The appearance of these bands in the IR and Raman spectra
      of some plants, tissues and pharmaceuticals confirms the presence of
      imidazopyridine skeleton in these substances.

PMID- 26314923
TI  - Discovery of oxathiapiprolin, a new oomycete fungicide that targets an oxysterol
      binding protein.
AB  - Oxathiapiprolin is the first member of a new class of piperidinyl thiazole
      isoxazoline fungicides with exceptional activity against plant diseases caused by
      oomycete pathogens. It acts via inhibition of a novel fungal target-an oxysterol
      binding protein-resulting in excellent preventative, curative and residual
      efficacy against key diseases of grapes, potatoes and vegetables. Oxathiapiprolin
      is being developed globally as DuPontTM ZorvecTM disease control with first
      registration and sales anticipated in 2015. The discovery, synthesis,
      optimization and biological efficacy are presented. 

PMID- 26314924
TI  - Ridaifen G, tamoxifen analog, is a potent anticancer drug working through a
      combinatorial association with multiple cellular factors.
AB  - Ridaifen-G (RID-G), a tamoxifen analog that we previously synthesized, has potent
      growth inhibitory activity against various cancer cell lines. Tamoxifen is an
      anticancer drug known to act on an estrogen receptor (ER) and other proteins.
      However, our previous studies interestingly suggested that the mechanism of
      action of RID-G was different from that of tamoxifen. In order to investigate the
      molecular mode of action of RID-G, we developed a novel chemical genetic approach
      that combined a phage display screen with a statistical analysis of drug potency
      and gene expression profiles in thirty-nine cancer cell lines. Application of
      this method to RID-G revealed that three proteins, calmodulin (CaM),
      heterogeneous nuclear ribonucleoproteins A2/B1 (hnRNP A2/B1), and zinc finger
      protein 638 (ZNF638) were the candidates of direct targets of RID-G. Moreover,
      cell lines susceptible to RID-G show similar expression profiles of RID-G target
      genes. These results suggest that RID-G involves CaM, hnRNP A2/B1, and ZNF638 in
      its growth inhibitory activity.

PMID- 26314925
TI  - Discovery, synthesis and biological evaluation of 2-(4-(N
      phenethylsulfamoyl)phenoxy)acetamides (SAPAs) as novel sphingomyelin synthase 1
      inhibitors.
AB  - Sphingomyelin synthase (SMS) has been proved to be a potential drug target for
      the treatment of atherosclerosis. However, few SMS inhibitors have been reported.
      In this paper, structure-based virtual screening was performed on hSMS1. SAPA 1a
      was discovered as a novel SMS1 inhibitor with an IC50 value of 5.2 MUM in
      enzymatic assay. A series of 2-(4-(N-phenethylsulfamoyl)phenoxy)acetamides
      (SAPAs) were synthesized and their biological activities toward SMS1 were
      evaluated. Among them, SAPA 1j was found to be the most potent SMS1 inhibitor
      with an IC50 value of 2.1 MUM in in vitro assay. The molecular docking studies
      suggested the interaction modes of SMS1 inhibitors and PC with the active site of
      SMS1. Site-directed mutagenesis validated the involvement of residues Arg342 and
      Tyr338 in enzymatic sphingomyelin production. The discovery of SAPA derivatives
      as a novel class of SMS1 inhibitors would advance the development of more
      effective SMS1 inhibitors.

PMID- 26314926
TI  - Mouse Clicks and Key Strokes.

PMID- 26314927
TI  - The role of hydroxyethyl groups in the construction of wormlike micelles in the
      system of quaternary ammonium surfactant and sodium salicylate.
AB  - To understand the role of electrostatic interactions and hydrogen bonds in the
      formation of wormlike micelles with the aid of sodium salicylate, two quaternary
      ammonium surfactants with the headgroup decorated by one hydroxyethyl group N
      cetyl-N-(2-hydroxyethyl)dimethylammonium bromide and two hydroxyethyl groups N
      cetyl-N,N-di(2-hydroxyethyl)methylammonium bromide, abbreviated as CHEMAB and
      CDHAB, respectively, were synthesized in this work. Single crystal X-ray
      diffraction was used to study the intermolecular interactions of surfactants, and
      (1)H NMR and rheological measurements were employed to investigate the molecular
      arrangement and morphology of the wormlike micelles. The synergistic interactions
      of hydrogen bonding and more effective shielding of electrostatic repulsion
      contribute to the formation and viscoelastic behavior of wormlike micelles. The
      results also revealed the aggregation behavior of surfactants with hydroxyethyl
      headgroups in aqueous solutions. 

PMID- 26314928
TI  - An optical nanoruler based on a conjugated polymer-silver nanoprism pair for
      label-free protein detection.
AB  - An optical nanoruler system based on a conjugated polyelectrolyte-silver
      nanoprism pair is developed for label-free protein detection by taking advantage
      of the metal-enhanced fluorescence effect of silver nanostructures. Antibody
      antigen interactions induce a change in the metal-fluorophore distance, followed
      by the response of a fluorescent signal of the conjugated polyelectrolyte. The
      system is used to detect target antigens sensitively and selectively. 

PMID- 26314929
TI  - Role of Oestrogen alpha Receptors in Sociosexual Behaviour in Female Rats Housed
      in a Seminatural Environment.
AB  - The present study investigated the role of oestrogen receptor (ER)alpha in the
      ventromedial nucleus of the hypothalamus (VMN), the preoptic area (POA), the
      medial amygdala (MePD) and the bed nucleus of stria terminalis (BNST) in
      sociosexual behaviour in female rats. This was conducted in two sets of
      experiments, with the VMN and POA investigated in the first set, and the MePD and
      BNST in the second set. The VMN and POA received intense projections from the
      MePD and BNST. We used a short hairpin RNA encoded within an adeno-associated
      viral vector directed against the gene for ERalpha to reduce the number of
      ERalpha in the VMN or POA (first set of experiments) or in the BNST or MePD
      (second set of experiments) in female rats. The rats were housed in groups of
      four ovariectomised females and three males in a seminatural environment for 8
      days. Compared with traditional test set-ups, the seminatural environment
      provides an arena in which the rats can express their full behavioural
      repertoire, which allowed us to investigate multiple aspects of social and sexual
      behaviour in groups of rats. Behavioural observation was performed after
      oestrogen and progesterone injections. A reduction of ERalpha expression in the
      VMN or POA diminished the display of paracopulatory behaviours and lordosis
      responses compared to controls, whereas the lordosis quotient remained
      unaffected. This suggests that ERalpha in the VMN and POA play an important role
      in intrinsic sexual motivation. The reduction in ERalpha did not affect the
      social behaviour of the females, although the males sniffed and pursued the
      females with reduced ERalpha less than the controls. This suggests that the
      ERalpha in the VMN and POA is involved in the regulation of sexual attractiveness
      of females. The ERalpha in the MePD and BNST, on the other hand, plays no role in
      sociosexual behaviour. 

PMID- 26314930
TI  - Light-Induced Resistance Effect Observed in Nano Au Films Covered Two-Dimensional
      Colloidal Crystals.
AB  - Tailoring resistance response using periodic nanostructures is one of the key
      issues in the current research. Two-dimensional colloidal crystals (CCs)
      structure is one of popular periodic nanospheres' structures and most of reports
      are focused on anomalous transmission of light or biomedical applications. In
      this work, a light-induced resistance effect is observed on silicon-based Au
      films covered CCs, featuring a remarkable resistance change as much as 56% and
      resistance switching characteristic. The diffusion and recombination of
      photocarriers is the crucial factor for this effect. This finding will expand
      photoelectricity functionality and be useful for future development of CC-based
      photoelectric devices. 

PMID- 26314931
TI  - Temperament and self-based correlates of cooperative, competitive and
      individualistic learning preferences.
AB  - People vary in the extent to which they prefer cooperative, competitive or
      individualistic achievement tasks. In this research, we conducted two studies
      designed to investigate correlates and possible roots of these social
      interdependence orientations, namely approach and avoidance temperament, general
      self-efficacy, implicit theories of intelligence, and contingencies of self-worth
      based in others' approval, competition and academic competence. The results
      indicated that approach temperament, general self-efficacy and incremental theory
      were positively related, and entity theory was negatively related to cooperative
      preferences (|r| range from .11 to .41); approach temperament, general self
      efficacy, competition contingencies and academic competence contingencies were
      positively related to competitive preferences (|r| range from .16 to .46); and
      avoidance temperament, entity theory, competitive contingencies and academic
      competence contingencies were positively related, and incremental theory was
      negatively related to individualistic preferences (|r| range from .09 to .15).
      The findings are discussed with regard to the meaning of each of the three social
      interdependence orientations, cultural differences among the observed relations
      and implications for practitioners.

PMID- 26314932
TI  - Robust light transport in non-Hermitian photonic lattices.
AB  - Combating the effects of disorder on light transport in micro- and nano
      integrated photonic devices is of major importance from both fundamental and
      applied viewpoints. In ordinary waveguides, imperfections and disorder cause
      unwanted back-reflections, which hinder large-scale optical integration.
      Topological photonic structures, a new class of optical systems inspired by
      quantum Hall effect and topological insulators, can realize robust transport via
      topologically-protected unidirectional edge modes. Such waveguides are realized
      by the introduction of synthetic gauge fields for photons in a two-dimensional
      structure, which break time reversal symmetry and enable one-way guiding at the
      edge of the medium. Here we suggest a different route toward robust transport of
      light in lower-dimensional (1D) photonic lattices, in which time reversal
      symmetry is broken because of the non-Hermitian nature of transport. While a
      forward propagating mode in the lattice is amplified, the corresponding backward
      propagating mode is damped, thus resulting in an asymmetric transport insensitive
      to disorder or imperfections in the structure. Non-Hermitian asymmetric transport
      can occur in tight-binding lattices with an imaginary gauge field via a non
      Hermitian delocalization transition, and in periodically-driven superlattices.
      The possibility to observe non-Hermitian delocalization is suggested using an
      engineered coupled-resonator optical waveguide (CROW) structure. 

PMID- 26314934
TI  - Diamond burr debridement of 34 canine corneas with presumed corneal calcareous
      degeneration.
AB  - OBJECTIVES: To describe the signalment, presence of systemic and/or ocular
      comorbidities, times to detected healing and probabilities of recurrence after
      diamond burr debridement (DBD) of eyes with presumed corneal calcareous
      degeneration and secondary ulceration and/or ocular pain. ANIMALS STUDIED: Twenty
      six dogs with 42 eyes affected, 34 eyes treated with DBD. METHODS: A case series
      was conducted using medical records from a private veterinary ophthalmology
      referral practice. Dogs were included if they had white or gray corneal opacity
      consistent with corneal calcareous degeneration with either erosive or
      superficial ulceration and/or ocular pain in at least one eye and had at least
      one such eye treated with DBD. DBD was performed with a battery-operated handheld
      motorized burr (The Alger Company, Inc. Lago Vista, TX, USA), and a bandage
      contact lens was placed in the majority of eyes (30/34). Eyes were considered
      healed when the cornea was fluorescein negative, and there were no signs of
      ocular pain. Patient data (signalment, recurrence) were extracted from medical
      records. RESULTS: Dogs were first re-examined 7-62 days after treatment (median:
      13 days). All DBD-treated eyes healed within 62 days (% healed: 100%; one-sided
      97.5% CI: 90-100%, median: 14 days), 82% of eyes (28/34) were healed at first re
      examination (median: 13 days after treatment), and all were healed by their
      second examination (median: 24 days). Of the 34 treated eyes, 11 were lost to
      follow up; 11 of the remaining 23 eyes recurred. Estimated 1-year recurrence
      probability was 58% (95% CI: 35-83%). Seven dogs had systemic disease; 7 had a
      history of prior ocular disease or intraocular surgery. CONCLUSIONS: Diamond burr
      debridement is a safe and effective treatment for rapid resolution of superficial
      corneal ulceration and ocular pain secondary to presumed corneal calcareous
      degeneration in dogs.

PMID- 26314933
TI  - Dynein-deficient flagella respond to increased viscosity with contrasting changes
      in power and recovery strokes.
AB  - Changes in the flagellar waveform in response to increased viscosity were
      investigated in uniflagellate mutants of Chlamydomonas reinhardtii. We
      hypothesized that the waveforms of mutants lacking different dynein arms would
      change in different ways as viscosity was increased, and that these variations
      would illuminate the feedback pathways from force to dynein activity. Previous
      studies have investigated the effects of viscosity on cell body motion,
      propulsive force, and power in different mutants, but the effect on waveform has
      not yet been fully characterized. Beat frequency decreases with viscosity in wild
      type uniflagellate (uni1) cells, and outer dynein arm deficient (oda2) mutants.
      In contrast, the inner dynein arm mutant ida1 (lacking I1/f) maintains beat
      frequency at high viscosity but alters its flagellar waveform more than either
      wild-type or oda2. The ida1 waveform is narrower than wild-type, primarily due to
      an abbreviated recovery stroke; this difference is amplified at high viscosity.
      The oda2 mutant in contrast, maintains a consistent waveform at high and low
      viscosity with a slightly longer power stroke than wild-type. Analysis of the
      delays and shear displacements between bends suggest that direct force feedback
      in the outer dynein arm system may initiate switching of dynein activity. In
      contrast, I1/f dynein appears to delay switching, most markedly at the initiation
      of the power stroke, possibly by controlling inter-doublet separation.

PMID- 26314935
TI  - Bilateral epithelial-myoepithelial carcinoma of the parotid glands.
AB  - BACKGROUND: The most common histological diagnosis of bilateral parotid gland
      neoplasm is Warthin tumor. Bilateral malignant tumors of the parotid gland are
      extremely rare. METHODS: A 60-year-old man presented with a painless mass in the
      right preauricular area and an MRI scan showed multiple masses in the parotid
      glands, bilaterally. A standard superficial parotidectomy was performed on the
      right parotid gland followed by subtotal parotidectomy on the left. The diagnosis
      was synchronous bilateral epithelial-myoepithelial carcinoma arising in the
      parotid glands. RESULTS: Histopathology of the tumor on both sides indicated
      epithelial-myoepithelial carcinoma. There was no evidence of locoregional or
      remote disease during a 5-year follow-up period. CONCLUSION: Malignant tumors
      should be included in the differential diagnosis of bilateral parotid gland
      tumors. Management of unilateral malignant parotid tumors should involve careful
      observation of the contralateral parotid gland.

PMID- 26314936
TI  - Impact of severe ADAMTS13 deficiency on clinical presentation and outcomes in
      patients with thrombotic microangiopathies: the experience of the Harvard TMA
      Research Collaborative.
AB  - The Harvard TMA Research Collaborative is a multi-institutional registry-based
      effort to study thrombotic microangiopathies (TMA). Laboratory and clinical
      parameters were recorded for 254 cases of suspected autoimmune thrombotic
      thrombocytopenic purpura (TTP). Patients with severe ADAMTS13 deficiency
      (activity <=10%, N = 68) were more likely to be young, female and without a
      history of cancer treatment or transplantation. While all patients with severe
      deficiency were diagnosed with autoimmune TTP, those without severe deficiency
      frequently had disseminated intravascular coagulation, drug-associated TMA and
      transplant-related TMA. Patients with severe ADAMTS13 deficiency had superior
      overall survival at 360 d compared to those without severe deficiency (93.0% vs.
      47.5%, P < 0.0001). Almost all patients with severe deficiency received
      therapeutic plasma exchange (TPE), but the use of TPE in patients with ADAMTS13
      activity >10% varied significantly across the institutions in our consortium
      (13.2-63.8%, P < 0.0001). Nevertheless, 90-d mortality was not different in
      patients with ADAMTS13 activity >10% between the three hospitals (P = 0.98). Our
      data show that patients with severe ADAMTS13 deficiency represent a clinically
      distinct cohort that responds well to TPE. In contrast, TMA without severe
      ADAMTS13 deficiency is associated with increased mortality that may not be
      influenced by TPE. 

PMID- 26314937
TI  - The social organization of a sedentary life for residents in long-term care.
AB  - Worldwide, the literature reports that many residents in long-term care (LTC)
      homes are sedentary. In Canada, personal support workers (PSWs) provide most of
      the direct care in LTC homes and could play a key role in promoting activity for
      residents. The purpose of this institutional ethnographic study was to uncover
      the social organization of LTC work and to discover how this organization
      influenced the physical activity of residents. Data were collected in two LTC
      homes in Ontario, Canada through participant observations with PSWs and
      interviews with people within and external to the homes. Findings explicate the
      links between meals, lifts and transfers, and the LTC standards to reveal that
      physical activity is considered an add-on program in the purview of
      physiotherapists. Some of the LTC standards which are intended to product good
      outcomes for residents actually disrupt the work of PSWs making it difficult for
      them to respond to the physical activity needs of residents. This descriptive
      ethnographic account is an important first step in trying to find a solution to
      optimize real activities of daily living into life in LTC.

PMID- 26314938
TI  - Reply.

PMID- 26314939
TI  - Vesicular trafficking and salinity responses in plants.
AB  - Research spanning three decades has demonstrated that vesicles pinch off from the
      plasma membrane and traffic through the cytoplasm of plant cells, much as
      previously reported in animal cells. Although the well-conserved clathrin
      mediated mechanism of endocytosis has been well characterized, relatively little
      is known about clathrin-independent pathways in plants. Modulation of endocytosis
      by both physical stimuli and chemical ligands has been reported in plants. Here,
      we review the effect of salinity-one of the most deleterious environmental
      assaults-on endocytosis and intracellular trafficking.

PMID- 26314940
TI  - Chitinophaga barathri sp. nov., isolated from mountain soil.
AB  - A Gram-stain-negative, non-motile, rod-shaped, aerobic bacterium, designated
      strain YLT18T, was isolated from mountain cliff soil of Enshi Grand Canyon in
      China. The major menaquinone was menaquinone 7 (MK-7) and the predominant fatty
      acids (>5 %) were iso-C15 : 0, C16 : 1omega5c, iso-C17 : 0 3-OH, summed feature 3
      (C16 : 1omega7c/iso-C15 : 0 2-OH) and iso-C15 : 0 3-OH. The major polar lipids
      were phosphatidylethanolamine, two unknown aminophospholipids, two unknown
      aminolipids and two unknown polar lipids. The DNA G+C content was 55.4 mol%.
      According to phylogenetic analysis based on 16S rRNA gene sequences, strain
      YLT18T was related most closely to Chitinophaga niabensis JS13-10T ( = DSM
      24787T) and Chitinophaga cymbidii R156-2T ( = KCTC 23738T), with similarities of
      96.7 and 96.2 %, respectively. In addition, strain YLT18T showed obvious
      differences from the closely related species in terms of esterase (C4) activity,
      acid production from fructose and rhamnose, and sole carbon source utilization by
      arabinose and rhamnose. The results from this polyphasic taxonomic study revealed
      that strain YLT18T represents a novel species of the genus Chitinophaga, for
      which the name Chitinophaga barathri sp. nov. is proposed. The type strain is
      YLT18T ( = KCTC 42472T = CCTCC AB 2015054T).

PMID- 26314942
TI  - Enzymatically Triggered, Isothermally Responsive Polymers: Reprogramming
      Poly(oligoethylene glycols) To Respond to Phosphatase.
AB  - Polymers which can respond to externally applied stimuli have found much
      application in the biomedical field due to their (reversible) coil-globule
      transitions. Polymers displaying a lower critical solution temperature are the
      most commonly used, but for blood-borne (i.e., soluble) biomedical applications
      the application of heat is not always possible, nor practical. Here we report the
      design and synthesis of poly(oligoethylene glycol methacrylate)-based polymers
      whose cloud points are easily varied by alkaline phosphatase-mediated
      dephosphorylation. By fine-tuning the density of phosphate groups on the
      backbone, it was possible to induce an isothermal transition: A change in
      solubility triggered by removal of a small number of phosphate esters from the
      side chains activating the LCST-type response. As there was no temperature change
      involved, this serves as a model of a cell-instructed polymer response. Finally,
      it was found that both polymers were non cytotoxic against MCF-7 cells (at 1
      mg.mL(-1)), which confirms promise for biomedical applications. 

PMID- 26314941
TI  - Food insecurity is associated with diabetes self-care behaviours and glycaemic
      control.
AB  - AIMS: Food insecurity is the 'limited or uncertain availability of nutritionally
      adequate and safe foods'. Our objective was to examine the association between
      food insecurity, diabetes self-care and glycaemic control. METHODS: We conducted
      a cross-sectional analysis of baseline data from adult patients with Type 2
      diabetes who were enrolled in a randomized trial evaluating a health literacy
      focused diabetes intervention in safety net primary care clinics in middle
      Tennessee. Food insecurity was assessed with three items from the U.S. Household
      Food Security Survey. Diabetes self-care behaviours were assessed with the
      Summary of Diabetes Self-Care Activities Scale, Personal Diabetes Questionnaire
      and Adherence to Refills and Medication Scale. Glycaemic control was assessed
      with HbA1c . RESULTS: The sample consisted of 401 participants, 73% of whom
      reported some level of food insecurity. Food insecurity was significantly
      associated with self-care behaviours including less adherence to a general diet
      [Adjusted Odds Ratio (AOR) 0.9, P = 0.02], less physical activity (AOR 0.9, P =
      0.04) and with a greater occurrence of medication non-adherence (AOR 1.2, P =
      0.002) and calorie restriction (AOR 1.1, P = 0.02). Food insecurity was also
      associated with worse glycaemic control (adjusted beta = 0.1, P = 0.03). None of
      the self-care behaviours were significantly associated with HbA1c , limiting the
      ability to test for self-care as a mechanism linking food insecurity to glycaemic
      control. CONCLUSIONS: There was a high rate of food insecurity in a sample of
      patients with Type 2 diabetes who were of low socio-economic status. Food
      insecurity was associated with less adherence to recommended self-care behaviours
      and worse glycaemic control.

PMID- 26314943
TI  - Involvement of Mast Cells in alpha7 Nicotinic Receptor Agonist Exacerbation of
      Freund's Complete Adjuvant-Induced Monoarthritis in Mice.
AB  - OBJECTIVE: Activation of antiinflammatory cholinergic (vagal) pathways can reduce
      inflammation, and in vitro studies support a pivotal role of alpha7 nicotinic
      acetylcholine receptors (alpha7-nAChR), macrophages, and T cells in these events.
      The aim of this study was to assess alpha7-nAChR agonists as an antiinflammatory
      treatment for Freund's complete adjuvant (CFA)-induced monoarthritis. METHODS:
      Arthritis was induced by intraarticular injection of CFA unilaterally into the
      knee joints of mice. Animals were treated with alpha7-nAChR agonists (AR-R17779
      or A844606), with or without antagonists (COG133 or methyllycaconitine), and
      joint inflammation and pain were assessed. Experiments were repeated in c-Kit(W
      sh) mast cell-deficient mice, and the effects of an alpha7-nAChR agonist on mast
      cell proliferation, migration, and activation by lipopolysaccharide (LPS) were
      tested. RESULTS: Treatment with alpha7-nAChR agonists significantly exacerbated
      CFA-induced arthritis and pain, as gauged by all indices of assessment, the
      specificity of which was confirmed by coadministration of an nAChR antagonist
      that attenuated the increase in disease severity. Toluidine blue-positive mast
      cells were increased in the joint capsule of CFA plus AR-R17779-treated mice, and
      AR-R17779 enhanced LPS-induced TNF proliferation and migration of a human mast
      cell line. The AR-R17779-driven increase in severity of CFA-induced arthritis was
      significantly reduced in mast cell-deficient mice. CONCLUSION: Using CFA to
      elicit a local inflammatory response, we found that pharmacologic activation of
      alpha7-nAChR exacerbated joint inflammation and pain, in part via mast cells,
      which illustrates the organ- and disease-specific nature of regulatory
      neuroimmune mechanisms. Thus, alpha7-nAChR activation may not be uniformly
      antiinflammatory in all types of inflammatory joint disease.

PMID- 26314944
TI  - Role of imaging in testicular cancer: current and future practice.
AB  - The article provides a summary of the epidemiologic and clinical aspects of
      testicular malignancy. Current standard imaging and novel techniques are
      reviewed. Present data and clinical treatment trends have favored surveillance
      protocols over adjuvant radiation or chemotherapy for low-stage testicular
      malignancy. This has resulted in increasing numbers of imaging studies and the
      potential for increased long-term exposure risks. Understanding imaging
      associated risks as well as strategies to minimize these risks is of increasing
      importance. The development, validation and incorporation of alternative lower
      risk highly efficacious and cost-effective imaging techniques is essential. 

PMID- 26314945
TI  - Dynamic Amygdala Influences on the Fronto-Striatal Brain Mechanisms Involved in
      Self-Control of Impulsive Desires.
AB  - Human decisions are guided by a variety of motivational factors, such as
      immediate rewards, long-term goals, and emotions. We used functional magnetic
      resonance imaging to investigate the dynamic functional interactions between the
      amygdala, the nucleus accumbens, and the prefrontal cortex that underlie the
      influences of emotions, desires, and rationality on human decisions. We found
      that increased functional connectivity between the amygdala and the nucleus
      accumbens facilitated the approach of an immediate reward in the presence of
      emotional information. Further, increased functional interactions of the
      anteroventral prefrontal cortex with the amygdala and the nucleus accumbens were
      associated with rational decisions in dilemma situations. These findings support
      previous animal studies by demonstrating that emotional signals from the amygdala
      and goal-oriented information from prefrontal cortices interface in the nucleus
      accumbens to guide human decisions and reward-directed actions. 

PMID- 26314947
TI  - MAC value of desflurane may vary for different machines.

PMID- 26314946
TI  - Postnatal xenogeneic B-cell tolerance in swine following in utero intraportal
      antigen exposure.
AB  - BACKGROUND: The objective of this study was to investigate the humoral immune
      response to xenogeneic antigens administered during the fetal state utilizing a
      baboon-to-pig model. METHODS: Nine fetuses from an alpha-1,3
      galactosyltransferase gene knockout (GalT-KO) MGH-miniature swine sow underwent
      transuterine ultrasound-guided intraportal injection of T-cell depleted baboon
      bone marrow (B-BM) at mid-gestation. Two juvenile GalT-KO swine undergoing direct
      B-BM intraportal injection were used as controls. RESULTS: Postnatal humoral
      tolerance was induced in the long-term surviving piglets as demonstrated by the
      absence of any antibody response to baboon donor cells. In addition, a second
      intraportal B-BM administration at 2.5 months post-birth led to no antibody
      formation despite re-exposure to xenogeneic antigens. This B-cell
      unresponsiveness was abrogated only when the animal was exposed subcutaneously to
      third-party xenogeneic and allogeneic antigens, suggesting that the previously
      achieved humoral non-responsiveness was donor specific. In comparison, the two
      juvenile GalT-KO control swine demonstrated increasing anti-baboon IgM and IgG
      levels following intraportal injection. CONCLUSIONS: In summary, xenogeneic B
      cell tolerance was induced through in utero intraportal exposure to donor cells
      and this tolerance persisted following postnatal rechallenge with donor B-BM, but
      was lost on exposure to third-party antigen, possibly as a result of cross
      reactive antibody formation.

PMID- 26314948
TI  - Acute intraoperative neurogenic myocardial stunning during intracranial
      endoscopic fenestration and shunt revision in a pediatric patient.
AB  - Neurogenic stunned myocardium (NSM) is syndrome of myocardial dysfunction
      following an acute neurological insult. We report a case of NSM that occurred
      intraoperatively in a pediatric patient undergoing endoscopic fenestration and
      shunt revision. Accidental outflow occlusion of irrigation fluid and ventricular
      distension resulted in an acute increase in heart rate and arterial blood
      pressure. Subsequently, the patient developed stunned myocardium with global
      myocardial hypokinesia and pulmonary edema. She was promptly treated
      intraoperatively then admitted to the pediatric intensive care unit with
      resolution of her symptoms within 12 h. She was later discharged to home on the
      fourth postoperative day. In the current endoscopic era, this report highlights
      the possibility of intraoperative NSM and neurogenic pulmonary edema in the
      pediatric population. Early detection and treatment with a team approach help to
      achieve optimal control of this life-threatening condition and improve the
      outcome. 

PMID- 26314950
TI  - Sequential Amniotic Fluid Thyroid Hormone Changes Correlate with Goiter Shrinkage
      following in utero Thyroxine Therapy.
AB  - Several isolated reports of fetal goiter treatment have shown limited
      generalizability of approaches and provide no real guidance for optimal timing,
      dosages, and treatment strategies. Graves' disease accounts for >60% of these
      cases. Maternal treatments of hyperthyroidism include antithyroid medications
      such as methimazole and more commonly propylthiouracil (PTU). Here, our
      management of a patient with a fetal thyroid goiter from maternal exposure to PTU
      diagnosed at 23.6 weeks' gestation and the management of other cases allow us
      propose a general strategy for treatment. Intrauterine therapy with 200 and then
      400 MUg of levothyroxine (3 weeks apart) showed an 85% reduction in fetal thyroid
      goiter volume. We collected amniotic fluid samples at the time of treatments and
      assayed thyroid hormones and associated antibodies which closely reflected the
      changes in thyroid goiter mass volume. Our observations suggest a weekly or
      biweekly therapeutic intervention schedule. Utilizing both goiter size as well as
      a novel approach in using amniotic fluid hormone levels to monitor therapy
      efficacy might improve the quality of treatments. Only with a standardized
      approach and collection of amniotic fluid thyroid panels do we have the
      opportunity to develop the database required to determine the number and timing
      of treatments needed. 

PMID- 26314949
TI  - Concentration-Dependent Diversifcation Effects of Free Cholesterol Loading on
      Macrophage Viability and Polarization.
AB  - BACKGROUND/AIMS: The accumulation of free cholesterol in atherosclerotic lesions
      has been well documented in both animals and humans. In studying the relevance of
      free cholesterol buildup in atherosclerosis, contradictory results have been
      generated, indicating that free cholesterol produces both pro- and anti
      atherosclerosis effects in macrophages. This inconsistency might stem from the
      examination of only select concentrations of free cholesterol. In the present
      study, we sought to investigate the implication of excess free cholesterol
      loading in the pathophysiology of atherosclerosis across a broad concentration
      range from (in ug/ml) 0 to 60. METHODS: Macrophage viability was determined by
      measuring formazan formation and flow cytometry viable cell counting. The
      polarization of M1 and M2 macrophages was differentiated by FACS (Fluorescence
      Activated Cell Sorting) assay. The secretion of IL-1beta in macrophage culture
      medium was measured by ELISA kit. Macrophage apoptosis was detected by flow
      cytometry using a TUNEL kit. RESULTS: Macrophage viability was increased at the
      treatment of lower concentrations of free cholesterol from (in ug/ml) 0 to 20,
      but gradually decreased at higher concentrations from 20 to 60. Lower free
      cholesterol loading induced anti-inflammatory M2 macrophage polarization. The
      activation of the PPARx03B3; (Peroxisome Proliferator-Activated Receptor gamma)
      nuclear factor underscored the stimulation of this M2 phenotype. Nevertheless,
      higher levels of free cholesterol resulted in pro-inflammatory M1 activation.
      Moreover, with the application of higher free cholesterol concentrations,
      macrophage apoptosis and secretion of the inflammatory cytokine IL-1beta
      increased significantly. CONCLUSION: These results for the first time demonstrate
      that free cholesterol could render concentration-dependent diversification
      effects on macrophage viability, polarization, apoptosis and inflammatory
      cytokine secretions, thereby reconciling the pros and cons of free cholesterol
      buildup in macrophages to the pathophysiology of atherosclerosis.

PMID- 26314951
TI  - Activation of alpha-diazocarbonyls by organic catalysts: diazo group acting as a
      strong N-terminal electrophile.
AB  - For the first time alpha-diazocarbonyls have been used as highly active N
      terminal electrophiles in the presence of bicyclic amidine catalysts. The C?N
      bond-forming reactions of active methylene compounds as C nucleophiles with alpha
      diazocarbonyls as N-terminal electrophiles proceed quickly under ambient
      conditions, in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), because
      of the formation of the reactive N-terminal electrophilic intermediates. DBU
      activates both the active methylene and alpha-diazocarbonyl. Importantly, this
      reaction is general for both active methylenes and alpha-diazocarbonyls, and the
      activation mode will lead to new synthetic applications of alpha-diazocarbonyls. 

PMID- 26314952
TI  - Physiological characteristics of patients with schizophrenia prematurely dying
      from circulatory diseases.
AB  - INTRODUCTION: Patients with schizophrenia before reaching geriatric age are at
      high risk of circulatory mortality. However, investigations are lacking on the
      characteristics of physiological measurement among these at-risk patients.
      METHODS: In this study, we followed acutely inpatients with schizophrenia
      disorder for cause of death through record linkage to the Death Certification
      System in Taiwan. Cases of patients who died because of circulatory morbidity
      (ICD-9 401-443) before turning 65 years old were used. Each schizophrenia case
      was then matched with two mentally healthy controls for the age and sex, and date
      of laboratory examination. Clinical data of all subjects were obtained by
      reviewing medical records. RESULTS: Totally, 81 patients with schizophrenia who
      died from circulatory diseases at mean ages of 48.0 +/- 10.7 years were
      investigated. The mean age at the final acute psychiatric hospitalization was
      43.0 +/- 10.9 years. Multivariate analysis showed that elevated fasting serum
      glucose levels (95% confidence interval [CI] for odds ratio (OR) = 1.00-1.03),
      blood leukocyte counts (95% CI for odds ratio (OR) = 1.07-1.55), and heart rates
      on electrocardiogram (95% CI for OR = 1.04-1.10) in the final psychiatric
      hospitalization collectively provided the predictive validity for premature
      circulatory death. CONCLUSION: Systemic inflammatory activation and autonomic
      nervous system dysfunction along with dysregulation of glucose metabolism rather
      than lipids could be the physiological characteristics of schizophrenia patients
      at risk of premature circulatory mortality.

PMID- 26314954
TI  - Nano "Chocolate Waffle" for near-IR Responsive Drug Releasing System.
AB  - A majority of the photo-responsive drug-delivery systems that are currently being
      studied require a complicated synthesis method. Here, we prepare a near-infrared
      responsive, photothermally controllable, drug-delivery carrier by a simple mixing
      and extraction process without the incorporation of toxic chemicals. A blend of
      doxorubicin (DOX), an anticancer drug, and a phase-change material (PCM) are
      loaded onto the mesoporous structure of silica-coated graphene oxide (GO@MS) to
      form a waffle-like structure, which is confirmed by various physicochemical
      analyses. The cytotoxicity of DOX/PCM-loaded GO@MS (DOX/PCM-GO@MS) against HeLa
      cells is 50 times higher than that of free DOX, and this improved activity can be
      attributed to the photothermal effectiveness of GO@MS. Additionally, the
      cytotoxicity and uptake mechanism of the PCM-based material are analyzed by flow
      cytometry. Taken together, our results suggest an enormous potential for spatio
      temporal control in photothermally responsive drug-delivery systems. 

PMID- 26314953
TI  - Relations of Postload and Fasting Glucose With Incident Cardiovascular Disease
      and Mortality Late in Life: The Cardiovascular Health Study.
AB  - BACKGROUND: Older adults have a high prevalence of postload hyperglycemia.
      Postload glucose has shown more robust associations with cardiovascular disease
      (CVD) and death than fasting glucose, but data in the oldest old are sparse.
      METHODS: Fasting and 2-hour postload glucose were measured in community-dwelling
      older adults, mean age 78, at the 1996-1997 follow-up visit of the Cardiovascular
      Health Study. We evaluated their associations with atherosclerotic CVD (ASCVD)
      and mortality using standard Cox regression and competing-risks analyses and
      assessed improvement in prediction-model discrimination with the c-statistic.
      RESULTS: Among 2,394 participants without treated diabetes and available data on
      glycemic measures, there were 579 ASCVD events and 1,698 deaths during median
      follow-up of 11.2 years. In fully adjusted models, both fasting and 2-hour
      glucose were associated with ASCVD (HR per SD, 1.13 [1.03-1.25] and 1.17 [1.07
      1.28], respectively) and all-cause mortality (HR 1.12 [1.07-1.18] and 1.14 [1.08
      1.20]). After mutual adjustment, however, the associations for fasting glucose
      with both outcomes were abolished, but those for postload glucose were largely
      unchanged. Consistent findings were observed for ASCVD in competing-risks models.
      CONCLUSION: In adults surviving to advanced old age, postload glucose was
      associated with ASCVD and mortality independently of fasting glucose, but fasting
      glucose was not associated with these outcomes independently of postload glucose.
      These findings affirm the robust association of postload glucose with ASCVD and
      death late in life.

PMID- 26314955
TI  - Commentary to paper "Primary versus secondary delayed gastric emptying (DGE)
      grades B and C of the International Study Group of Pancreatic Surgery after
      pancreatoduodenectomy: a retrospective analysis on a group of 132 patients".

PMID- 26314956
TI  - Inhibition of Lon protease by triterpenoids alters mitochondria and is associated
      to cell death in human cancer cells.
AB  - Mitochondrial Lon protease (Lon) regulates several mitochondrial functions, and
      is inhibited by the anticancer molecule triterpenoid 2-cyano-3, 12-dioxooleana
      1,9(11)-dien-28-oic acid (CDDO), or by its C-28 methyl ester derivative (CDDO
      Me). To analyze the mechanism of action of triterpenoids, we investigated
      intramitochondrial reactive oxygen species (ROS), mitochondrial membrane
      potential, mitochondrial mass, mitochondrial dynamics and morphology, and Lon
      proteolytic activity in RKO human colon cancer cells, in HepG2 hepatocarcinoma
      cells and in MCF7 breast carcinoma cells. We found that CDDO and CDDO-Me are
      potent stressors for mitochondria in cancer cells, rather than normal non
      transformed cells. In particular, they: i) cause depolarization; ii) increase
      mitochondrial ROS, iii) alter mitochondrial morphology and proteins involved in
      mitochondrial dynamics; iv) affect the levels of Lon and those of aconitase and
      human transcription factor A, which are targets of Lon activity; v) increase
      level of protein carbonyls in mitochondria; vi) lead to intrinsic apoptosis. The
      overexpression of Lon can rescue cells from cell death, providing an additional
      evidence on the role of Lon in conditions of excessive stress load. 

PMID- 26314957
TI  - Hepatitis B virus-associated diffuse large B-cell lymphoma: unique clinical
      features, poor outcome, and hepatitis B surface antigen-driven origin.
AB  - While the epidemiologic association between hepatitis B virus (HBV) infection and
      diffuse large B-cell lymphoma (DLBCL) is established, little is known more than
      this epidemiologic evidence. We studied a cohort of 587 patients with DLBCL for
      HBV infection status, clinicopathologic features, and the immunoglobulin variable
      region in HBV surface antigen (HBsAg)-positive patients. Eighty-one (81/587,
      13.8%) patients were HBsAg-positive. Compared with HBsAg-negative DLBCL, HBsAg
      positive DLBCL displayed a younger median onset age (45 vs. 55 years), more
      frequent involvement of spleen or retroperitoneal lymph node (40.7% vs. 16.0% and
      61.7% vs. 31.0% respectively, both p < 0.001), more advanced disease (stage
      III/IV: 76.5% vs 59.5%, p = 0.003), and significantly worse outcome (2-year
      overall survival: 47% versus 70%, p < 0.001). In HBsAg-positive DLBCL patients,
      almost all (45/47, 96%) amino acid sequences of heavy and light chain
      complementarity determining region 3 exhibited a high homology to antibodies
      specific for HBsAg, and the majority (45/50, 90%) of IgHV and IgLV genes were
      mutated. We conclude that 13.8% of DLBCL cases are HBV-associated in HBV-endemic
      China and show unique clinical features and poor outcomes. Furthermore, our study
      strongly suggests that HBV-associated DLBCL might arise from HBV antigen-selected
      B cells. 

PMID- 26314958
TI  - Tolerance and dose-volume relationship of intrathoracic stomach irradiation after
      esophagectomy for patients with thoracic esophageal squamous cell carcinoma.
AB  - PURPOSE: To identify the tolerance of radiation with a high prescribed dose and
      predictors for the development of intrathoracic stomach toxicity in patients with
      thoracic esophageal squamous cell carcinoma (SCC) after esophagectomy followed by
      gastric conduit reconstruction. MATERIALS AND METHODS: From 2011 to 2013, 105
      patients after esophagectomy were treated with postoperative radiotherapy. The
      intrathoracic stomach was outlined with the calculation of a dose-volume
      histogram (DVH) for the initial intended treatment of 6020 cGy or 6300 cGy. The
      volume of the intrathoracic stomach receiving each dose was recorded at 10-Gy
      intervals between 10 and 40 Gy and at 5-Gy intervals between 40 and 60 Gy. The
      grade of toxicities was defined by the National Cancer Institute Common Toxicity
      Criteria version 4.0. RESULTS: The mean and maximum doses of the intrathoracic
      stomach were 2449 +/- 986 cGy and 6519 +/- 406 cGy, respectively. Sixteen (15.2%)
      and three (2.9%) experienced Common Toxicity Criteria Grade 2 and Grade 3 acute
      gastric toxicity. There were no Grade 4 toxicities. Fourteen patients (13.3%)
      exhibited late gastric complications possibly related to radiation. The volume
      percent of the intrathoracic stomach receiving at least 50 Gy (V50) was strongly
      associated with the degree of toxicity (p = 0.024, respectively). Multivariate
      analysis of patient and treatment-related factors revealed no other significant
      predictors of severe toxicities. CONCLUSIONS: The intrathoracic stomach is well
      tolerated with a high-dose irradiation for patients with esophageal SCC receiving
      radiotherapy after esophagectomy. A strong dose-volume relationship exists for
      the development of Grade 2 acute intrathoracic stomach toxicity in our study.

PMID- 26314959
TI  - MiR-625-3p promotes cell migration and invasion via inhibition of SCAI in
      colorectal carcinoma cells.
AB  - MicroRNAs (miRNAs) play a critical role in controlling tumor invasion and
      metastasis via regulating the expression of a variety of targets, which act as
      oncogenes or tumor suppressor genes. Abnormally expressed miR-625-3p has been
      observed in several types of human cancers. However, the molecular mechanisms of
      miR-625-3p-mediated tumorigenesis are largely elusive. Therefore, the aim of this
      study was to evaluate the biological function and molecular insight on miR-625-3p
      induced oncogenesis in colorectal carcinoma (CRC). The effects of miR-625-3p in
      cell migration and invasion were analyzed by wound healing assay and transwell
      assay, respectively. In addition, the expression of miR-625-3p and its targets
      was detected in five human CRC cell lines. In the present study, we found that
      overexpression of miR-625-3p promoted migration and invasion in SW480 cells,
      whereas downregulation of miR-625-3p inhibited cell motility in SW620 cells. More
      importantly, we observed potential binding sites for miR-625-3p in the 3'
      untranslated region of suppressor of cancer cell invasion (SCAI). Notably, we
      identified that overexpression of miR-625-3p inhibited the expression of SCAI,
      while depletion of miR-625-3p increased SCAI level, suggesting that SCAI could be
      a target of miR-625-3p. Additionally, we revealed that miR-625-3p exerts its
      oncogenic functions through regulation of SCAI/E-cadherin/MMP-9 pathways. Our
      findings indicate the pivotal role of miR-625-3p in invasion that warrants
      further exploration whether targeting miR-625-3p could be a promising approach
      for the treatment of CRC. 

PMID- 26314960
TI  - Low doses of X-rays induce prolonged and ATM-independent persistence of gammaH2AX
      foci in human gingival mesenchymal stem cells.
AB  - Diagnostic imaging delivering low doses of radiation often accompany human
      mesenchymal stem cells (MSCs)-based therapies. However, effects of low dose
      radiation on MSCs are poorly characterized. Here we examine patterns of
      phosphorylated histone H2AX (gammaH2AX) and phospho-S1981 ATM (pATM) foci
      formation in human gingiva-derived MSCs exposed to X-rays in time-course and dose
      response experiments. Both gammaH2AX and pATM foci accumulated linearly with dose
      early after irradiation (5-60 min), with a maximum induction observed at 30-60
      min (37 +/- 3 and 32 +/- 3 foci/cell/Gy for gammaH2AX and pATM, respectively).
      The number of gammaH2AX foci produced by intermediate doses (160 and 250 mGy)
      significantly decreased (40-60%) between 60 and 240 min post-irradiation,
      indicating rejoining of DNA double-strand breaks. In contrast, gammaH2AX foci
      produced by low doses (20-80 mGy) did not change after 60 min. The number of pATM
      foci between 60 and 240 min decreased down to control values in a dose
      independent manner. Similar kinetics was observed for pATM foci co-localized with
      gammaH2AX foci. Collectively, our results suggest differential DNA double-strand
      break signaling and processing in response to low vs. intermediate doses of X
      rays in human MSCs. Furthermore, mechanisms governing the prolonged persistence
      of gammaH2AX foci in these cells appear to be ATM-independent. 

PMID- 26314961
TI  - STAT3 pathway regulates lung-derived brain metastasis initiating cell capacity
      through miR-21 activation.
AB  - Brain metastases (BM) represent the most common tumor to affect the adult central
      nervous system. Despite the increasing incidence of BM, likely due to
      consistently improving treatment of primary cancers, BM remain severely
      understudied. In this study, we utilized patient-derived stem cell lines from
      lung-to-brain metastases to examine the regulatory role of STAT3 in brain
      metastasis initiating cells (BMICs). Annotation of our previously described BMIC
      regulatory genes with protein-protein interaction network mapping identified
      STAT3 as a novel protein interactor. STAT3 knockdown showed a reduction in BMIC
      self-renewal and migration, and decreased tumor size in vivo. Screening of BMIC
      lines with a library of STAT3 inhibitors identified one inhibitor to
      significantly reduce tumor formation. Meta-analysis identified the oncomir
      microRNA-21 (miR-21) as a target of STAT3 activity. Inhibition of miR-21
      displayed similar reductions in BMIC self-renewal and migration as STAT3
      knockdown. Knockdown of STAT3 also reduced expression of known downstream targets
      of miR-21. Our studies have thus identified STAT3 and miR-21 as cooperative
      regulators of stemness, migration and tumor initiation in lung-derived BM.
      Therefore, STAT3 represents a potential therapeutic target in the treatment of
      lung-to-brain metastases. 

PMID- 26314962
TI  - Targeting the mRNA-binding protein HuR impairs malignant characteristics of
      pancreatic ductal adenocarcinoma cells.
AB  - Post-transcriptional regulation is a powerful mediator of gene expression, and
      can rapidly alter the expression of numerous transcripts involved in
      tumorigenesis. We have previously shown that the mRNA-binding protein HuR
      (ELAVL1) is elevated in human pancreatic ductal adenocarcinoma (PDA) specimens
      compared to normal pancreatic tissues, and its cytoplasmic localization is
      associated with increased tumor stage. To gain a better insight into HuR's role
      in PDA biology and to assess it as a candidate therapeutic target, we altered HuR
      expression in PDA cell lines and characterized the resulting phenotype in
      preclinical models. HuR silencing by short hairpin and small interfering RNAs
      significantly decreased cell proliferation and anchorage-independent growth, as
      well as impaired migration and invasion. In comparison, HuR overexpression
      increased migration and invasion, but had no significant effects on cell
      proliferation and anchorage-independent growth. Importantly, two distinct
      targeted approaches to HuR silencing showed marked impairment in tumor growth in
      mouse xenografts. NanoString nCounter(r) analyses demonstrated that HuR regulates
      core biological processes, highlighting that HuR inhibition likely thwarts PDA
      viability through post-transcriptional regulation of diverse signaling pathways
      (e.g. cell cycle, apoptosis, DNA repair). Taken together, our study suggests that
      targeted inhibition of HuR may be a novel, promising approach to the treatment of
      PDA. 

PMID- 26314963
TI  - Inhibition of poly(ADP-ribose) polymerase 1 protects against acute myeloid
      leukemia by suppressing the myeloproliferative leukemia virus oncogene.
AB  - An abnormal expression of poly(ADP-ribose) polymerase 1 (PARP-1) has been
      described in many tumors. PARP-1 promotes tumorigenesis and cancer progression by
      acting on different molecular pathways. PARP-1 inhibitors can be used with
      radiotherapy or chemotherapy to enhance the susceptibility of tumor cells to the
      treatment. However, the specific mechanism of PARP-1 in acute myeloid leukemia
      (AML) remains unknown. Our study showed that expression of PARP-1 was upregulated
      in AML patients. PARP-1 inhibition slowed AML cell proliferation, arrested the
      cell cycle, induced apoptosis in vitro and improved AML prognosis in vivo.
      Mechanistically, microarray assay of AML cells with loss of PARP-1 function
      revealed that the myeloproliferative leukemia virus oncogene (MPL) was
      significantly downregulated. In human AML samples, MPL expression was increased,
      and gain-of-function and loss-of-function analysis demonstrated that MPL promoted
      cell growth. Moreover, PARP-1 and MPL expression were positively correlated in
      AML samples, and their overexpression was associated with an unfavorable
      prognosis. Furthermore, PARP-1 and MPL consistently acted on Akt and ERK1/2
      pathways, and the anti-proliferative and pro-apoptotic function observed with
      PARP-1 inhibition were reversed in part via MPL activation upon thrombopoietin
      stimulation or gene overexpression. These data highlight the important function
      of PARP-1 in the progression of AML, which suggest PARP-1 as a potential target
      for AML treatment. 

PMID- 26314964
TI  - Resistance to anticancer vaccination effect is controlled by a cancer cell
      autonomous phenotype that disrupts immunogenic phagocytic removal.
AB  - Immunogenic cell death (ICD) is a well-established instigator of 'anti-cancer
      vaccination-effect (AVE)'. ICD has shown considerable preclinical promise, yet
      there remain subset of cancer patients that fail to respond to clinically-applied
      ICD inducers. Non-responsiveness to ICD inducers could be explained by the
      existence of cancer cell-autonomous, anti-AVE resistance mechanisms. However such
      resistance mechanisms remain poorly investigated. In this study, we have
      characterized for the first time, a naturally-occurring preclinical cancer model
      (AY27) that exhibits intrinsic anti-AVE resistance despite treatment with ICD
      inducers like mitoxantrone or hypericin-photodynamic therapy. Further mechanistic
      analysis revealed that this anti-AVE resistance was associated with a defect in
      exposing the important 'eat me' danger signal, surface-calreticulin (ecto
      CRT/CALR). In an ICD setting, this defective ecto-CRT further correlated with
      severely reduced phagocytic clearance of AY27 cells as well as the failure of
      these cells to activate AVE. Defective ecto-CRT in response to ICD induction was
      a result of low endogenous CRT protein levels (i.e. CRTlow-phenotype) in AY27
      cells. Exogenous reconstitution of ecto-rCRT (recombinant-CRT) improved the
      phagocytic removal of ICD inducer-treated AY27 cells, and importantly,
      significantly increased their AVE-activating ability. Moreover, we found that a
      subset of cancer patients of various cancer-types indeed possessed CALRlow or
      CRTlow-tumours. Remarkably, we found that tumoural CALRhigh-phenotype was
      predictive of positive clinical responses to therapy with ICD inducers
      (radiotherapy and paclitaxel) in lung and ovarian cancer patients, respectively.
      Furthermore, only in the ICD clinical setting, tumoural CALR levels positively
      correlated with the levels of various phagocytosis-associated genes relevant for
      phagosome maturation or processing. Thus, we reveal the existence of a cancer
      cell-autonomous, anti-AVE or anti-ICD resistance mechanism that has profound
      clinical implications for anticancer immunotherapy and cancer predictive
      biomarker analysis. 

PMID- 26314965
TI  - NKX6.3 controls gastric differentiation and tumorigenesis.
AB  - NKX6.3 transcription factor is known to be an important regulator in gastric
      mucosal epithelial differentiation. The present study aimed to investigate
      whether NKX6.3 acts as an essential tumor suppressor in gastric carcinogenesis.
      Absent or reduced protein expression and decreased DNA copy number and mRNA
      transcript of the NKX6.3 gene were frequently observed in gastric cancers.
      Overexpression of NKX6.3 in AGSNKX6.3 and MKN1NKX6.3 cells markedly arrested cell
      proliferation by inhibiting cell cycle progression and induced apoptosis through
      both death receptor- and mitochondrial-pathways. In addition, stable NKX6.3
      transfectants increased the expression of gastric differentiation markers,
      including SOX2 and Muc5ac, and decreased the expression of intestinal
      differentiation markers, CDX2 and Muc2. In ChIP-cloning and sequencing analyses,
      NKX6.3 coordinated a repertoire of target genes, some of which are clearly
      associated with cell cycle, differentiation and death. In particular, NKX6.3
      transcriptional factor was found to bind specifically to the upstream sequences
      of GKN1, a gastric-specific tumor suppressor, and dramatically increase
      expression of the latter. Furthermore, there was a positive correlation between
      NKX6.3 and GKN1 expression in non-cancerous gastric mucosae. Thus, these data
      suggest that NKX6.3 may control the fate of gastric mucosal cells and function as
      a gastric tumor suppressor. 

PMID- 26314967
TI  - Electronic cigarettes: the tobacco industry's latest threat to oral health?

PMID- 26314966
TI  - MiR-23a sensitizes nasopharyngeal carcinoma to irradiation by targeting IL
      8/Stat3 pathway.
AB  - Radioresistance poses a major challenge in nasopharyngeal carcinoma (NPC)
      treatment, but little is known about how miRNA regulates this phenomenon. In this
      study, we investigated the function and mechanism of miR-23a in NPC
      radioresistance, one of downregulated miRNAs in the radioresistant NPC cells
      identified by our previous microarray analysis. We observed that miR-23a was
      frequently downregulated in the radioresistant NPC tissues, and its decrement
      correlated with NPC radioresistance and poor patient survival, and was an
      independent predictor for reduced patient survival. In vitro radioresponse assays
      showed that restoration of miR-23a expression markedly increased NPC cell
      radiosensitivity. In a mouse model, therapeutic administration of miR-23a agomir
      dramatically sensitized NPC xenografts to irradiation. Mechanistically, we found
      that reduced miR-23a promoted NPC cell radioresistance by activating IL-8/Stat3
      signaling. Moreover, the levels of IL-8 and phospho-Stat3 were increased in the
      radioresistance NPC tissues, and negatively associated with miR-23a level. Our
      data demonstrate that miR-23a is a critical determinant of NPC radioresponse and
      prognostic predictor for NPC patients, and its decrement enhances NPC
      radioresistance through activating IL-8/Stat3 signaling, highlighting the
      therapeutic potential of miR-23a/IL-8/Stat3 signaling axis in NPC
      radiosensitization. 

PMID- 26314968
TI  - Dental terminology.

PMID- 26314969
TI  - Narrative and patient care.

PMID- 26314970
TI  - Authors' response.

PMID- 26314971
TI  - Emergency toothache.

PMID- 26314972
TI  - Emergency dental blocks.

PMID- 26314973
TI  - Maintaining standards.

PMID- 26314974
TI  - Authors' response.

PMID- 26314975
TI  - Occupational mercury exposure in association with prevalence of multiple
      sclerosis and tremor among US dentists.
AB  - BACKGROUND: The effects of chronic occupational exposure to elemental mercury
      (Hg(0)) are largely unknown. The objective was to evaluate the association of
      occupational Hg(0) exposure with multiple sclerosis (MS) and tremor. METHODS: The
      study included 13,906 dentists who attended the American Dental Association's
      annual meeting over 24 years (1986-2007 and 2011-2012). Participants reported MS
      and tremor and provided urine specimens for Hg(0) analysis. The authors estimated
      mean Hg(0) exposures over time and used logistic regression to estimate the
      associations of 3 Hg(0) exposure measures with MS or tremor. RESULTS: Among
      participants, 0.18% reported MS and 1.24% reported tremor. Hg(0) exposure was not
      associated with MS (odds ratio [OR] per 191 micrograms per liter in cumulative
      Hg(0) exposure, 0.85; 95% confidence interval [CI], 0.39-1.85). Increased
      prevalent risk of tremor was found with exposure to both urinary Hg(0) exposure
      (OR, 1.10 [95% CI, 1.00-1.22]) and cumulative Hg(0) exposure among younger
      dentists (< 51 years; OR, 1.13 [95% CI, 1.05-1.22]). CONCLUSIONS: Occupational
      Hg(0) exposure in US dentists decreased over time and now is approaching that of
      the general population. Our results suggest a positive association between Hg(0)
      exposure and tremor. PRACTICAL IMPLICATIONS: Studies with more sophisticated
      outcome and exposure measures, and including more retired dentists, would provide
      critical information toward understanding the relation of Hg(0) exposures to MS
      and tremor risk.

PMID- 26314976
TI  - Reporting quality of randomized controlled trial abstracts: survey of leading
      general dental journals.
AB  - BACKGROUND: The authors conducted a study to assess the reporting quality of
      randomized controlled trial (RCT) abstracts published in leading general dental
      journals, investigate any improvement after the release of the Consolidated
      Standards of Reporting Trials (CONSORT) for Abstracts guidelines, and identify
      factors associated with better reporting quality. METHODS: The authors searched
      PubMed for RCTs published in 10 leading general dental journals during the
      periods from 2005 to 2007 (pre-CONSORT period) and 2010 to 2012 (post-CONSORT
      period). The authors evaluated and scored the reporting quality of included
      abstracts by using the original 16-item CONSORT for Abstracts checklist. The
      authors used risk ratios and the t test to compare the adequate reporting rate of
      each item and the overall quality in the 2 periods. The authors used univariate
      and multivariate regressions to identify predictors of better reporting quality.
      RESULTS: The authors included and evaluated 276 RCT abstracts. Investigators
      reported significantly more checklist items during the post-CONSORT period (mean
      [standard deviation {SD}], 4.53 [1.69]) than during the pre-CONSORT period (mean
      [SD], 3.87 [1.10]; mean difference, -0.66 [95% confidence interval, -0.99 to 
      0.33]; P < .001). Investigators reported 3 items-interventions, objective, and
      conclusions-adequately in most of the abstracts (> 80%). In contrast, the authors
      saw sufficient reporting of randomization, recruitment, outcome in the results
      section, and funding in none of the pre-CONSORT abstracts and less than 2% of the
      post-CONSORT abstracts. On the basis of the multivariate analysis, a higher
      impact factor (P < .001) and a publication date in the post-CONSORT period (P =
      .003) were associated significantly with higher reporting quality. CONCLUSIONS:
      The reporting quality of RCT abstracts from leading general dental journals has
      improved significantly, but there is still room for improvement. PRACTICAL
      IMPLICATIONS: Joint efforts by authors, reviewers, journal editors, and other
      stakeholders to improve the reporting of dental RCT abstracts are needed.

PMID- 26314977
TI  - A practical approach to evidence-based dentistry: IX: how to appraise and use an
      article about economic analysis.
AB  - BACKGROUND AND OVERVIEW: In everyday practice, dentists face clinical decisions
      for which they need to consider both treatment consequences (that is, benefits
      and harms) and costs. Economic analysis is a study design in which investigators
      evaluate and compare the costs and consequences of different treatment
      alternatives within a defined period. A critical appraisal of such studies
      includes an assessment of the risk of bias, results, and applicability of the
      study. The authors provide the concepts and guidelines that dentists can apply to
      critically appraise economic analyses. PRACTICAL IMPLICATIONS: Dentists who wish
      to inform their clinical decisions regarding questions that involve both
      treatment consequences and costs can use these guidelines to understand the
      different types of economic analyses and to decide what type of economic analyses
      to search for, as well as to critically appraise any economic analyses
      identified.

PMID- 26314978
TI  - Oromandibular dystonia: differential diagnosis and management.

PMID- 26314979
TI  - Unilateral submandibular swelling.

PMID- 26314980
TI  - Limited evidence indicates fluoride may prevent demineralized white lesions
      during orthodontic treatment.

PMID- 26314981
TI  - How safe is deep sedation or general anesthesia while providing dental care?
AB  - BACKGROUND: Deep sedation and general anesthesia are administered daily in dental
      offices, most commonly by oral and maxillofacial surgeons and dentist
      anesthesiologists. METHODS: The goal of deep sedation or general anesthesia is to
      establish a safe environment in which the patient is comfortable and cooperative.
      This requires meticulous care in which the practitioner balances the patient's
      depth of sedation and level of responsiveness while maintaining airway integrity,
      ventilation, and cardiovascular hemodynamics. RESULTS: Using the available data
      and informational reports, the authors estimate that the incidence of death and
      brain injury associated with deep sedation or general anesthesia administered by
      all dentists most likely exceeds 1 per month. CONCLUSIONS: Airway compromise is a
      significant contributing factor to anesthetic complications. The American Society
      of Anesthesiology closed claim analysis also concluded that human error
      contributed highly to anesthetic mishaps. The establishment of a patient safety
      database for anesthetic management in dentistry would allow for a more complete
      assessment of morbidity and mortality that could direct efforts to further
      increase safe anesthetic care. PRACTICAL IMPLICATIONS: Deep sedation and general
      anesthesia can be safely administered in the dental office. Optimization of
      patient care requires appropriate patient selection, selection of appropriate
      anesthetic agents, utilization of appropriate monitoring, and a highly trained
      anesthetic team. Achieving a highly trained anesthetic team requires emergency
      management preparation that can foster decision making, leadership,
      communication, and task management.

PMID- 26314982
TI  - Ten metrics all dentists should monitor.

PMID- 26314983
TI  - Ethical concerns of working while ill: Presenteeism.

PMID- 26314984
TI  - Prognostic signature and clonality pattern of recurrently mutated genes in
      inactive chronic lymphocytic leukemia.
AB  - An increasing numbers of patients are being diagnosed with asymptomatic early
      stage chronic lymphocytic leukemia (CLL), with no treatment indication at
      baseline. We applied a high-throughput deep-targeted analysis, especially
      designed for covering widely TP53 and ATM genes, in 180 patients with inactive
      disease at diagnosis, to test the independent prognostic value of CLL somatic
      recurrent mutations. We found that 40/180 patients harbored at least one acquired
      variant with ATM (n=17, 9.4%), NOTCH1 (n=14, 7.7%), TP53 (n=14, 7.7%) and SF3B1
      (n=10, 5.5%) as most prevalent mutated genes. Harboring one 'sub-Sanger' TP53
      mutation granted an independent 3.5-fold increase of probability of needing
      treatment. Those patients with a double-hit ATM lesion (mutation+11q deletion)
      had the shorter median time to first treatment (17 months). We found that a
      genomic variable: TP53 mutations, most of them under the sensitivity of
      conventional techniques; a cell phenotypic factor: CD38-positive expression; and
      a classical marker as beta2-microglobulin, remained as the unique independent
      predictors of outcome. The high-throughput determination of TP53 status,
      particularly in this set of patients frequently lacking high-risk chromosomal
      aberrations, emerges as a key step, not only for prediction modeling, but also
      for exploring mutation-specific therapeutic approaches and minimal residual
      disease monitoring. 

PMID- 26314985
TI  - Brentuximab vedotin: axonal microtubule's Apollyon.

PMID- 26314986
TI  - Does day 11 omission of methotrexate due to toxicity influence the outcome in
      myeloablative hematopoietic cell transplant? Results from a single-center
      retrospective cohort study.

PMID- 26314987
TI  - Factors associated with an increased risk of vertebral fracture in monoclonal
      gammopathies of undetermined significance.
AB  - Monoclonal gammopathies of undetermined significance (MGUS) have been shown to be
      associated with an increased risk of fractures. This study describes
      prospectively the bone status of MGUS patients and determines the factors
      associated with vertebral fracture. We included prospectively 201 patients with
      MGUS, incidentally discovered, and with no known history of osteoporosis: mean
      age 66.6+/-12.5 years, 48.3% women, 51.7% immunoglobulin G (IgG), 33.3% IgM and
      10.4% IgA. Light chain was kappa in 64.2% patients. All patients had spinal
      radiographs and bone mineral density measurement in addition to gammopathy
      assessment. At least one prevalent non-traumatic vertebral fracture was
      discovered in 18.4% patients and equally distributed between men and women.
      Fractured patients were older, had a lower bone density and had also more
      frequently a lambda light chain isotype. Compared with patients with kappa light
      chain, the odds ratio of being fractured for patients with lambda light chain was
      4.32 (95% confidence interval 1.80-11.16; P=0.002). These results suggest a high
      prevalence of non-traumatic vertebral fractures in MGUS associated with lambda
      light chain isotype and not only explained by low bone density. 

PMID- 26314988
TI  - Whole-exome analysis reveals novel somatic genomic alterations associated with
      outcome in immunochemotherapy-treated diffuse large B-cell lymphoma.
AB  - Lack of remission or early relapse remains a major clinical issue in diffuse
      large B-cell lymphoma (DLBCL), with 30% of patients failing standard of care.
      Although clinical factors and molecular signatures can partially predict DLBCL
      outcome, additional information is needed to identify high-risk patients,
      particularly biologic factors that might ultimately be amenable to intervention.
      Using whole-exome sequencing data from 51 newly diagnosed and immunochemotherapy
      treated DLBCL patients, we evaluated the association of somatic genomic
      alterations with patient outcome, defined as failure to achieve event-free
      survival at 24 months after diagnosis (EFS24). We identified 16 genes with
      mutations, 374 with copy number gains and 151 with copy number losses that were
      associated with failure to achieve EFS24 (P<0.05). Except for FOXO1 and CIITA,
      known driver mutations did not correlate with EFS24. Gene losses were localized
      to 6q21-6q24.2, and gains to 3q13.12-3q29, 11q23.1-11q23.3 and 19q13.12-19q13.43.
      Globally, the number of gains was highly associated with poor outcome (P=7.4 *
      10(-12)) and when combined with FOXO1 mutations identified 77% of cases that
      failed to achieve EFS24. One gene (SLC22A16) at 6q21, a doxorubicin transporter,
      was lost in 54% of EFS24 failures and our findings suggest it functions as a
      doxorubicin transporter in DLBCL cells. 

PMID- 26314989
TI  - Upper Airway Elasticity Estimation in Pediatric Down Syndrome Sleep Apnea
      Patients Using Collapsible Tube Theory.
AB  - Elasticity of the soft tissues surrounding the upper airway lumen is one of the
      important factors contributing to upper airway disorders such as snoring and
      obstructive sleep apnea. The objective of this study is to calculate patient
      specific elasticity of the pharynx from magnetic resonance (MR) images using a
      'tube law', i.e., the relationship between airway cross-sectional area and
      transmural pressure difference. MR imaging was performed under anesthesia in
      children with Down syndrome (DS) and obstructive sleep apnea (OSA). An airway
      segmentation algorithm was employed to evaluate changes in airway cross-sectional
      area dilated by continuous positive airway pressure (CPAP). A pressure-area
      relation was used to make localized estimates of airway wall stiffness for each
      patient. Optimized values of patient specific Young's modulus for tissue in the
      velopharynx and oropharynx, were estimated from finite element simulations of
      airway collapse. Patient specific deformation of the airway wall under CPAP was
      found to exhibit either a non-linear 'hardening' or 'softening' behavior. The
      localized airway and tissue elasticity were found to increase with increasing
      severity of OSA. Elasticity based patient phenotyping can potentially assist
      clinicians in decision making on CPAP and airway or tissue elasticity can
      supplement well-known clinical measures of OSA severity. 

PMID- 26314990
TI  - Sustained Efficacy and Arterial Drug Retention by a Fast Drug Eluting Cross
      Linked Fatty Acid Coronary Stent Coating.
AB  - The long held assumption that sustained drug elution from stent coatings over
      weeks to months is imperative for clinical efficacy has limited the choice for
      stent coating materials. We developed and evaluated an omega-3 fatty acid (O3FA)
      based stent coating that is 85% absorbed and elutes 97% of its Sirolimus analog
      (Corolimus) load within 8d of implantation. O3FA coated stents sustained drug
      levels in porcine coronary arteries similarly to those achieved by slow-eluting
      durable coated Cypher Select Plus Stents and with significantly lower levels of
      granuloma formation and luminal stenosis. Computational modeling confirmed that
      diffusion and binding constants of Corolimus and Sirolimus are identical and
      explained that the sustained retention of Corolimus was facilitated by binding to
      high affinity intracellular receptors (FKBP12). First in man outcomes were
      positive-unlike Cypher stents where late lumen loss drops over 6 month, there was
      a stable effect without diminution in the presence of O3FA. These results speak
      to a new paradigm whereby the safety of drug eluting stents can be optimized
      through the use of resorbable biocompatible coating materials with resorption
      kinetics that coincide with the dissociation and tissue elimination of receptor
      bound drug. 

PMID- 26314991
TI  - Individual differences and correlates of highly superior autobiographical memory.
AB  - Highly superior autobiographical memory (HSAM) is a recently identified ability
      that has been difficult to explain with existing memory science. The present
      study measured HSAM participants' and age/gender-matched controls' on a number of
      behavioural measures to test three main hypotheses: imaginative absorption,
      emotional arousal, and sleep. HSAM participants were significantly higher than
      controls on the dispositions absorption and fantasy proneness. These two
      dispositions also were associated with a measure of HSAM ability within the
      hyperthymesia participants. The emotional-arousal hypothesis yielded only weak
      support. The sleep hypothesis was not supported in terms of quantity, but sleep
      quality may be a small factor worthy of further research. Other individual
      differences are also documented using a predominantly exploratory analysis.
      Speculative pathways describing how the tendencies to absorb and fantasise could
      lead to enhanced autobiographical memory are discussed.

PMID- 26314992
TI  - Letter to the editor: subchondral calcium phosphate is ineffective for bone
      marrow edema lesions in adults with advanced osteoarthritis.

PMID- 26314993
TI  - Cochrane in CORR ((r)): Continuous Passive Motion Following Total Knee
      Arthroplasty in People With Arthritis (Review).

PMID- 26314994
TI  - Editorial: Case Closed-Discontinuing Case Reports in Clinical Orthopaedics and
      Related Research.

PMID- 26314995
TI  - CORR Insights((r)): THA revisions using impaction allografting with mesh is
      durable for medial but not lateral acetabular defects.

PMID- 26314996
TI  - Anterior cingulate implants for tinnitus: report of 2 cases.
AB  - Tinnitus can be distressful, and tinnitus distress has been linked to increased
      beta oscillatory activity in the dorsal anterior cingulate cortex (dACC). The
      amount of distress is linked to alpha activity in the medial temporal lobe
      (amygdala and parahippocampal area), as well as the subgenual (sg)ACC and insula,
      and the functional connectivity between the parahippocampal area and the sgACC at
      10 and 11.5 Hz. The authors describe 2 patients with very severely distressing
      intractable tinnitus who underwent transcranial magnetic stimulation (TMS) with a
      double-cone coil targeting the dACC and subsequent implantation of electrodes on
      the dACC. One of the patients responded to the implant and one did not, even
      though phenomenologically they both expressed the same tinnitus loudness and
      distress. The responder has remained dramatically improved for more than 2 years
      with 6-Hz burst stimulation of the dACC. The 2 patients differed in functional
      connectivity between the area of the implant and a tinnitus network consisting of
      the parahippocampal area as well as the sgACC and insula; that is, the responder
      had increased functional connectivity between these areas, whereas the
      nonresponder had decreased functional connectivity between these areas. Only the
      patient with increased functional connectivity linked to the target area of
      repetitive TMS or implantation might transmit the stimulation current to the
      entire tinnitus network and thus clinically improve. 

PMID- 26314997
TI  - Various patterns of the middle cerebral vein and preservation of venous drainage
      during the anterior transpetrosal approach.
AB  - OBJECTIVE: The drainage of the superficial middle cerebral vein (SMCV) has
      previously been classified into 4 subtypes. Extradural procedures and dural
      incisions during the anterior transpetrosal approach (ATPA) may interrupt the
      route of drainage from the SMCV. In this study, the authors examined the
      relationship between anatomical variations in the SMCV and the corresponding
      surgical modifications to the ATPA that are necessary for venous preservation.
      METHODS: This study included 48 patients treated via the ATPA in whom the SMCV
      was examined using 3D CT venography. The drainage patterns of the SMCV were
      classified into 3 types: cavernous or absent (Type 1), sphenobasal (Type 2), and
      sphenopetrosal (Type 3). Type 2 was subdivided into medial (Type 2a) and lateral
      (Type 2b), and Type 3 was subdivided into vein (Type 3a), vein and sinus (Type
      3b), and sinus (Type 3c). The authors performed 3 ATPA modifications to preserve
      the SMCV: epidural anterior petrosectomy with subdural visualization of the
      sphenobasal vein (SBV), modification of the dural incision, and subdural anterior
      petrosectomy. Standard ATPA can be performed with Type 1, Type 2a, and Type 3a
      drainage. With Type 2b drainage, an epidural anterior petrosectomy with subdural
      SBV visualization is appropriate. The dural incision should be modified in Type
      3b. With Type 3c, a subdural anterior petrosectomy is required. RESULTS: The
      frequency of each type was 68.7% (33/48) in Type 1, 8.3% (4/48) in Type 2a, 4.2%
      (2/48) in Type 2b, 14.6% (7/48) in Type 3a, 2.1% (1/48) in Type 3b, and 2.1%
      (1/48) in Type 3c. No venous complications were found. CONCLUSIONS: The authors
      propose an SMCV modified classification based on ATPA modifications required for
      venous preservation.

PMID- 26314999
TI  - Low dose rate brachytherapy for the treatment of brain metastases.

PMID- 26314998
TI  - A Phase I proof-of-concept and safety trial of sildenafil to treat cerebral
      vasospasm following subarachnoid hemorrhage.
AB  - OBJECTIVE: Studies show that phosphodiesterase-V (PDE-V) inhibition reduces
      cerebral vasospasm (CVS) and improves outcomes after experimental subarachnoid
      hemorrhage (SAH). This study was performed to investigate the safety and effect
      of sildenafil (an FDA-approved PDE-V inhibitor) on angiographic CVS in SAH
      patients. METHODS: A2-phase, prospective, nonrandomized, human trial was
      implemented. Subarachnoid hemorrhage patients underwent angiography on Day 7 to
      assess for CVS. Those with CVS were given 10 mg of intravenous sildenafil in the
      first phase of the study and 30 mg in the second phase. In both, angiography was
      repeated 30 minutes after infusion. Safety was assessed by monitoring
      neurological examination findings and vital signs and for the development of
      adverse reactions. For angiographic assessment, in a blinded fashion, pre- and
      post-sildenafil images were graded as "improvement" or "no improvement" in CVS.
      Unblinded measurements were made between pre- and post-sildenafil angiograms.
      RESULTS: Twelve patients received sildenafil; 5 patients received 10 mg and 7
      received 30 mg. There were no adverse reactions. There was no adverse effect on
      heart rate or intracranial pressure. Sildenafil resulted in a transient decline
      in mean arterial pressure, an average of 17% with a return to baseline in an
      average of 18 minutes. Eight patients (67%) were found to have a positive
      angiographic response to sildenafil, 3 (60%) in the low-dose group and 5 (71%) in
      the high-dose group. The largest degree of vessel dilation was an average of 0.8
      mm (range 0-2.1 mm). This corresponded to an average percentage increase in
      vessel diameter of 62% (range 0%-200%). CONCLUSIONS: The results from this Phase
      I safety and proof-of-concept trial assessing the use of intravenous sildenafil
      in patients with CVS show that sildenafil is safe and well tolerated in the
      setting of SAH. Furthermore, the angiographic data suggest that sildenafil has a
      positive impact on human CVS.

PMID- 26315000
TI  - Patient factors associated with 30-day morbidity, mortality, and length of stay
      after surgery for subdural hematoma: a study of the American College of Surgeons
      National Surgical Quality Improvement Program.
AB  - OBJECTIVE: Surgery for subdural hematoma (SDH) is a commonly performed
      neurosurgical procedure. This study identifies patient characteristics associated
      with adverse outcomes and prolonged length of stay (LOS) in patients who
      underwent surgical treatment for SDH. METHODS: All patients in the American
      College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) who
      were treated via craniotomy or craniectomy for SDH between 2005 and 2012 were
      identified. Patient demographics, comorbidities, and 30-day outcomes were
      described. Multivariate regression was used to identify predictors of adverse
      events. RESULTS: A total of 746 surgical procedures performed for SDH were
      identified and analyzed. Patients undergoing this procedure were 64% male with an
      average age (+/- SD) of 70.9 +/- 14.1 years. The most common individual adverse
      events were death (17%) and intubation for more than 48 hours (19%). In total,
      34% experienced a serious adverse event other than death, 8% of patients returned
      to the operating room (OR), and the average hospital LOS was 9.8 +/- 9.9 days. In
      multivariate analysis, reduced mortality was associated with age less than 60
      years (relative risk [RR] = 0.47, p = 0.017). Increased mortality was associated
      with gangrene (RR = 3.5, p = 0.044), ascites (RR = 3.00, p = 0.006), American
      Society of Anesthesiologists (ASA) Class 4 or higher (RR = 2.34, p = 0.002), coma
      (RR = 2.25, p < 0.001), and bleeding disorders (RR = 1.87, p = 0.003). Return to
      the OR was associated with pneumonia (RR = 3.86, p = 0.044), male sex (RR = 1.85,
      p = 0.015), and delirium (RR = 1.75, p = 0.016). Serious adverse events were
      associated with ventilator dependence preoperatively (RR = 1.86, p < 0.001),
      dialysis (RR = 1.44, p = 0.028), delirium (RR = 1.40, p = 0.005), ASA Class 4 or
      higher (RR = 1.36, p = 0.035), and male sex (RR = 1.29, p = 0.037). Similarly,
      LOS was increased in ventilator dependent patients by 1.56-fold (p = 0.002), in
      patients with ASA Class 4 or higher by 1.30-fold (p = 0.006), and in delirious
      patients by 1.29-fold (p = 0.008). CONCLUSIONS: Adverse outcomes are common after
      surgery for SDH. In this study, 18% of the patients died within 30 days of
      surgery. Factors associated with adverse outcomes were identified. Patients and
      families should be counseled about the serious risks of morbidity and death
      associated with acute traumatic SDH requiring surgery.

PMID- 26315001
TI  - Cocaine use as an independent predictor of seizures after aneurysmal subarachnoid
      hemorrhage.
AB  - OBJECTIVE: Seizures are relatively common after aneurysmal subarachnoid
      hemorrhage (aSAH). Seizure prophylaxis is controversial and is often based on
      risk stratification; middle cerebral artery (MCA) aneurysms, associated
      intracerebral hemorrhage (ICH), poor neurological grade, increased clot
      thickness, and cerebral infarction are considered highest risk for seizures. The
      purpose of this study was to evaluate the impact of recent cocaine use on seizure
      incidence following aSAH. METHODS: Prospectively collected data from aSAH
      patients admitted to 2 institutional neuroscience critical care units between
      1991 and 2009 were reviewed. The authors analyzed factors that potentially
      affected the incidence of seizures, including patient demographic
      characteristics, poor clinical grade (Hunt and Hess Grade IV or V), medical
      comorbidities, associated ICH, intraventricular hemorrhage (IVH), hydrocephalus,
      aneurysm location, surgical clipping and cocaine use. They further studied the
      impact of these factors on "early" and "late" seizures (defined, respectively, as
      occurring before and after clipping/coiling). RESULTS: Of 1134 aSAH patients
      studied, 182 (16%) had seizures; 81 patients (7.1%) had early and 127 (11.2%)
      late seizures, with 26 having both. The seizure rate was significantly higher in
      cocaine users (37 [26%] of 142 patients) than in non-cocaine users (151 [15.2%]
      of 992 patients, p = 0.001). Eighteen cocaine-positive patients (12.7%) had early
      seizures compared with 6.6% of cocaine-negative patients (p = 0.003); 27 cocaine
      users (19%) had late seizures compared with 10.5% non-cocaine users (p = 0.001).
      Factors that showed a significant association with increased risk for seizure
      (early or late) on univariate analysis included younger age (< 40 years) (p =
      0.009), poor clinical grade (p = 0.029), associated ICH (p = 0.007), and MCA
      aneurysm location (p < 0.001); surgical clipping was associated with late
      seizures (p = 0.004). Following multivariate analysis, age < 40 years (OR 2.04,
      95% CI 1.355-3.058, p = 0.001), poor clinical grade (OR 1.62, 95% CI 1.124-2.336,
      p = 0.01), ICH (OR 1.95, 95% CI 1.164-3.273, p = 0.011), MCA aneurysm location
      (OR 3.3, 95% CI 2.237-4.854, p < 0.001), and cocaine use (OR 2.06, 95% CI 1.330
      3.175, p = 0.001) independently predicted seizures. CONCLUSIONS: Cocaine use
      confers a higher seizure risk following aSAH and should be considered during risk
      stratification for seizure prophylaxis and close neuromonitoring.

PMID- 26315002
TI  - Angiographic findings of in-stent intimal hyperplasia after stent-assisted coil
      embolization: are they permanent findings?
AB  - OBJECTIVE: Stent-assisted coil embolization for the treatment of intracranial
      aneurysms has been used widely. This study aimed to investigate the effect of
      stent implantation in the nonatherosclerotic parent artery with cerebral
      aneurysms. The authors evaluated luminal changes and the related factors
      following stent-assisted coil embolization. METHODS: This study included 97
      patients harboring a total of 99 unruptured aneurysms of the distal internal
      carotid artery (ICA) who underwent single-stent implantation and more than 1
      session of conventional angiography during follow-up (midterm follow-up only, n =
      70; midterm and long-term follow-up, n = 29) between January 2009 and April 2014.
      The luminal narrowing point was measured using a local thickness map (ImageJ plug
      in). RESULTS: Stent-assisted coil embolization caused dynamic luminal narrowing
      of approximately 82% of the parent artery diameter on average after 8 months,
      which was reversed to 91% after 25 months. In addition, luminal narrowing greater
      than 40% was noticed in 2 (7%) of the 29 patients who experienced spontaneous
      reversion without additional management during follow-up. Most luminal narrowing
      changes seen were diffuse. CONCLUSIONS: Luminal narrowing after aneurysm stent
      assisted coil embolization is a dynamic process and appears to be a spontaneously
      reversible event. Routine management of luminal narrowing may not cause adverse
      events that require additional treatment.

PMID- 26315004
TI  - A double-blind randomized trial on the clinical effect of different shunt valve
      settings in idiopathic normal pressure hydrocephalus.
AB  - OBJECTIVE: The study aim was to examine the effect of gradually reducing the
      opening pressure on symptoms and signs in the shunt treatment of idiopathic
      normal pressure hydrocephalus (iNPH). METHODS: In this prospective double
      blinded, randomized, controlled, double-center study on patients with iNPH, a
      ventriculoperitoneal shunt with an adjustable Codman Medos Valve was implanted in
      68 patients randomized into 2 groups. In 1 group (the 20-4 group) the valve
      setting was initially set to 20 cm H2O and gradually reduced to 4 cm H2O over the
      course of the 6-month study period. In the other group (the 12 group), the valve
      was kept at a medium level of 12 cm H2O during the whole study period. All
      patients were clinically evaluated using 4 tests preoperatively as well as
      postoperatively at 1, 2, 3, 4, and 6 months. The test scores between the 2 groups
      (20-4 and 12) were compared for each clinical evaluation. RESULTS: Fifty-five
      patients (81%) were able to complete the study. There were no significant
      differences between the 2 groups (20-4 and 12) preoperatively or at any time
      postoperatively. Both groups exhibited significant clinical improvement after
      shunt insertion at all valve settings compared with the preoperative score, with
      the greatest improvement observed at the first postoperative evaluation. The
      clinical improvement was significant within the first 3 months, and thereafter no
      significant improvement was seen in either group. CONCLUSIONS: Gradual reduction
      of the valve setting from 20 to 4 cm H2O did not improve outcome compared with a
      fixed valve setting of 12 cm H2O. Improvement after shunt surgery in iNPH
      patients was evident within 3 months, irrespective of valve setting.

PMID- 26315005
TI  - Comparison of endoscope- versus microscope-assisted resection of deep-seated
      intracranial lesions using a minimally invasive port retractor system.
AB  - OBJECTIVE: Tubular brain retractors may improve access to deep-seated brain
      lesions while potentially reducing the risks of collateral neurological injury
      associated with standard microsurgical approaches. Here, microscope-assisted
      resection of lesions using tubular retractors is assessed to determine if it is
      superior to endoscope-assisted surgery due to the technological advancements
      associated with modern tubular ports and surgical microscopes. METHODS: Following
      institutional approval of the tubular port, data obtained from the initial 20
      patients to undergo transportal resection of deep-seated brain lesions were
      analyzed in this study. The pathological entities of the resected tissues
      included metastatic tumors (8 patients), glioma (7), meningioma (1), neurocytoma
      (1), radiation necrosis (1), primitive neuroectodermal tumor (1), and
      hemangioblastoma (1). Surgery incorporated endoscopic (5 patients) or microscopic
      (15) assistance. The locations included the basal ganglia (11 patients),
      cerebellum (4), frontal lobe (2), temporal lobe (2), and parietal lobe (1). Cases
      were reviewed for neurological outcomes, extent of resection (EOR), and
      complications. Technical data for the port, surgical microscope, and endoscope
      were analyzed. RESULTS: EOR was considered total in 14 (70%), near total (> 95%)
      in 4 (20%), and subtotal (< 90%) in 2 (10%) of 20 patients. Incomplete resection
      was associated with the basal ganglia location (p < 0.05) and use of the
      endoscope (p < 0.002). Four of 5 (80%) endoscope-assisted cases were near-total
      (2) or subtotal (2) resection. Histopathological diagnosis, presenting
      neurological symptoms, and demographics were not associated with EOR.
      Complication rates were low and similar between groups. CONCLUSIONS: Initial
      experience with tubular retractors favors use of the microscope rather than the
      endoscope due to a wider and 3D field of view. Improved microscope optics and
      tubular retractor design allows for binocular vision with improved lighting for
      the resection of deep-seated brain lesions.

PMID- 26315003
TI  - Association of traumatic brain injury with subsequent neurological and
      psychiatric disease: a meta-analysis.
AB  - OBJECTIVE: Mild traumatic brain injury (TBI) has been proposed as a risk factor
      for the development of Alzheimer's disease, Parkinson's disease, depression, and
      other illnesses. This study's objective was to determine the association of prior
      mild TBI with the subsequent diagnosis (that is, at least 1 year postinjury) of
      neurological or psychiatric disease. METHODS: All studies from January 1995 to
      February 2012 reporting TBI as a risk factor for diagnoses of interest were
      identified by searching PubMed, study references, and review articles. Reviewers
      abstracted the data and assessed study designs and characteristics. RESULTS:
      Fifty-seven studies met the inclusion criteria. A random effects meta-analysis
      revealed a significant association of prior TBI with subsequent neurological and
      psychiatric diagnoses. The pooled odds ratio (OR) for the development of any
      illness subsequent to prior TBI was 1.67 (95% CI 1.44-1.93, p < 0.0001). Prior
      TBI was independently associated with both neurological (OR 1.55, 95% CI 1.31
      1.83, p < 0.0001) and psychiatric (OR 2.00, 95% CI 1.50-2.66, p < 0.0001)
      outcomes. Analyses of individual diagnoses revealed higher odds of Alzheimer's
      disease, Parkinson's disease, mild cognitive impairment, depression, mixed
      affective disorders, and bipolar disorder in individuals with previous TBI as
      compared to those without TBI. This association was present when examining only
      studies of mild TBI and when considering the influence of study design and
      characteristics. Analysis of a subset of studies demonstrated no evidence that
      multiple TBIs were associated with higher odds of disease than a single TBI.
      CONCLUSIONS: History of TBI, including mild TBI, is associated with the
      development of neurological and psychiatric illness. This finding indicates that
      either TBI is a risk factor for heterogeneous pathological processes or that TBI
      may contribute to a common pathological mechanism.

PMID- 26315006
TI  - Randomized controlled trials and neurosurgery: the ideal fit or should
      alternative methodologies be considered?
AB  - OBJECTIVE: Randomized-controlled trials (RCTs) are advocated to provide high
      level medical evidence. However, in neurosurgery, there are barriers to
      conducting RCTs. The authors of this study sought to analyze the quality of
      neurosurgical RCTs since 2000 to determine the adequacy of their design and
      reporting. METHODS: A search of the MEDLINE and EMBASE databases (2000-2014) was
      conducted. The medical subject heading (MeSH) terms used in the search included:
      "neurosurgery" OR "neurosurgical procedure," "brain neoplasms," "infarction" and
      "decompression," "carotid stenosis," "cerebral hemorrhage," and "spinal fusion."
      These studies were limited to RCTs, in humans, and in the English language. The
      Consolidated Standards for Reporting of Trials (CONSORT) and Jadad scales were
      used to assess the quality of RCT design and reporting. The standardized median
      times cited (median citations divided by years since publication) were used to
      assess impact. A pragmatic-explanatory continuum indicator summary-based scale
      was used to assess the design of the studies as primarily pragmatic or
      explanatory. RESULTS: Sixty-one articles were identified, and the following
      subspecialties were the most common: vascular (23, 37%), followed by functional
      neurosurgery and neurooncology (both 13, 21%). The following nations were the
      primary leaders in RCTs: US (25 studies, 41%), Germany (8 studies, 13%), and the
      United Kingdom (7 studies, 11%). Median sample size was 100 (interquartile range
      [IQR] 41.5-279). The majority of the studies (40, 66%) had pragmatic objectives.
      The median number of times cited overall was 69 (IQR 20.5-193). The combined
      median CONSORT score was 36 (IQR 27.5-39). Blinding was most deficiently
      reported. Other areas with a relatively low quality of reporting were sample size
      calculation (34.2% of surgical, 38.5% of drug, and 20% of device studies),
      allocation concealment (28.9% of surgical, 23.1% of drug, and 50% of device
      studies), and protocol implementation (18.4% of surgical, 23% of drug, and 20% of
      device studies). The quality of reporting did not correlate with the study
      impact. All studies had a median Jadad score <= 3. Thirty-three pragmatic studies
      (83%) and 5 explanatory studies (25%) met the design objectives. All pragmatic
      studies based on drug and device trials met their objectives, while 74% of
      pragmatic surgical trials met their objectives. CONCLUSIONS: The prevalence of
      neurosurgical RCTs is low. The quality of RCT design and reporting in
      neurosurgery is also low. Many study designs are not compatible with stated
      objectives. Pragmatic studies were more likely to meet design objectives. Given
      the role of RCTs as one of the highest levels of evidence, it is critical to
      improve on their methodology and reporting.

PMID- 26315007
TI  - Malignant fungal infection of the cavernous sinus: case report.
AB  - Intracranial spread of fungal infection is a life-threatening condition that
      usually affects immunocompromised patients. Here the authors present a case of
      biopsy-proven Aspergillus fumigatus infection of the paranasal sinuses in an
      immunocompetent patient with documented spread to the orbit, cavernous sinus, and
      petrous apex despite medical antifungal treatment. As a life-saving treatment,
      cavernous sinus resection with external carotid artery-middle cerebral artery
      bypass was performed. The authors discuss the literature regarding the
      intracranial spread of paranasal sinus fungal infections in immunocompetent
      patients and management strategies. 

PMID- 26315008
TI  - Editorial: Randomized clinical trials and neurosurgery.

PMID- 26315009
TI  - Report of whole-brain radiation therapy in a patient with an implanted deep brain
      stimulator: important neurosurgical considerations and radiotherapy practice
      principles.
AB  - Patients with implanted neuromodulation devices present potential challenges for
      radiation therapy treatment planning and delivery. Although guidelines exist
      regarding the irradiation of cardiac pacemakers and defibrillators, fewer data
      and less clinical experience exist regarding the effects of radiation therapy on
      less frequently used devices, such as deep brain stimulators. A 79-year-old woman
      with a history of coarse tremors effectively managed with deep brain stimulation
      presented with multiple intracranial metastases from a newly diagnosed lung
      cancer and was referred for whole-brain radiation therapy. She was treated with a
      German helmet technique to a total dose of 30 Gy in 10 fractions using 6 MV
      photons via opposed lateral fields with the neurostimulator turned off prior to
      delivery of each fraction. The patient tolerated the treatment well with no acute
      complications and no apparent change in the functionality of her neurostimulator
      device or effect on her underlying neuromuscular disorder. This represents the
      first reported case of the safe delivery of whole-brain radiation therapy in a
      patient with an implanted neurostimulator device. In cases such as this,
      neurosurgeons and radiation oncologists should have discussions with patients
      about the risks of brain injury, device malfunction or failure of the device, and
      plans for rigorous testing of the device before and after radiation therapy. 

PMID- 26315010
TI  - Editorial: Temporal lobe venous preservation.

PMID- 26315011
TI  - CSF leak in transsphenoidal surgery.

PMID- 26315012
TI  - [Complicated course of a laparoscopic cholecystectomy].
AB  - The case presented deals with the complicated course of a laparoscopic
      cholecystectomy in a 45-year-old female patient due to cholecystolithiasis. The
      patient complained that during the operation an injury to the small intestine
      occurred, which was only operatively treated at midday of the despite massive
      pain and insufficient pain treatment. The intervention was claimed to have
      resulted in mental and physical suffering. The case is assessed by two
      independent experts in the sense of a "scientifically founded comment" with
      respect to the decision of the arbitration board and taking the surgical
      standards into consideration. 

PMID- 26315013
TI  - [Stenosis and ulceration after bariatric surgery].
AB  - INTRODUCTION: The increasing number of morbidly obese patients leads to a rising
      number of bariatric procedures in Germany. The operative techniques are highly
      standardized but such a standardization is lacking for the management of
      postoperative complications such as stenosis and ulceration after Roux-en-Y
      gastric bypass (RYGB) surgery and sleeve gastrectomy (SG). METHODS: The current
      literature is reviewed and a complication management is developed and presented
      in this article. RESULTS AND CONCLUSION: Postoperative stenoses occure with a
      frequency of 0.1-3.9% after SG and 3-27% after RYGB. Stenosis is secondary to
      inadequate surgical technique or microinsufficiency. Ulcers can be due to
      reaction to foreign body, local ischemia, peptic lesion, fistula and
      microinsufficiency. CONCLUSION: Endoscopic interventions are successful in most
      cases for stenosis after RYGB and for short stenoses after SG. After SG long
      stenoses require redo surgery and conversion to RYGB. Ulcers can be managed by
      medication with the exception of perforation and hemorrhage, which require
      emergency laparoscopy.

PMID- 26315014
TI  - Stenting in malignant colonic obstruction--is it a real therapeutic option?
AB  - BACKGROUND: Malignant colonic obstruction is commonly treated surgically. Colonic
      stents are a therapeutic option for palliation or used as a bridge to surgery or
      chemotherapy. OBJECTIVE: The aim of the study was to evaluate the clinical
      success rate of stenting as a bridge to one-step surgery, chemotherapy, or as a
      palliative measure. DESIGN: This was a retrospective observational study.
      SETTINGS: The study was conducted at a university-affiliated tertiary referral
      center. PATIENTS AND INTERVENTIONS: From 2007 to 2014, 45 patients with malignant
      colonic obstruction were referred for stent insertion. MAIN OUTCOME MEASURES:
      Patients were grouped according to three pre-defined treatment goals: group 1:
      restorative one-step procedure without an ostomy, group 2: completion of
      scheduled chemotherapy before surgery, and group 3: palliation without surgical
      intervention. RESULTS: Group 1 included 11 patients. Three patients (27.3 %) met
      the treatment goal of one-step surgery. Eight patients (72.7 %) did not reach the
      primary goal due to stent insertion failure (four patients), stent-related
      complications (two patients), and failure to perform a one-step surgery after
      successful stent insertion (two patients). Group 2 included 12 patients.
      Chemotherapy was successfully completed prior to surgery in six patients (50 %).
      Six patients (50 %) did not achieve treatment goal due to stent insertion failure
      (two patients), stent migration (two patients), stent-related perforation (one
      patient), and mortality (one patient). Group 3 included 20 patients. Long-term
      palliation without surgical intervention was achieved in eight patients (40 %).
      Stent insertion failed in seven patients (35 %). Five patients (25 %) needed
      urgent surgery due to stent complications (three migrations and two
      perforations). LIMITATIONS: The study was limited by its retrospective nature and
      small sample size. CONCLUSIONS: This study demonstrates only a modest success
      rate of colonic stents in the treatment of malignant colonic obstruction.
      Although colonic stenting seems to be an effective method of relieving colonic
      obstruction, high failure rates limits its applicability.

PMID- 26315016
TI  - Real world dehiscence rates for patients undergoing abdominoperineal resection
      with or without myocutaneous flap closure in the national surgical quality
      improvement project.
AB  - PURPOSE: Perineal wound complications cause significant morbidity following
      abdominoperineal resection (APR). Myocutaneous flap closure may mitigate perineal
      wound complications though data is limited outside of specialized oncologic
      centers. We aim to compare rates of wound dehiscence in patients undergoing APR
      with and without flap closure. METHODS: All patients undergoing APR in the
      National Surgical Quality Improvement Program between 2005 and 2013 were
      included. Thirty-day rate of wound dehiscence and other perioperative outcomes
      were compared between the flap and non-flap cohorts. Subgroup analysis was
      performed for propensity score-matched cohorts and those receiving neoadjuvant
      radiation. RESULTS: Seven thousand two hundred and five patients underwent non
      emergent APR [527 (7 %) flap vs. 6678 (93 %) non-flap]. Wound dehiscence occurred
      in 224 patients [38 (7 %) flap vs. 186 (3 %) non-flap] with 84/224 (38 %) of
      these reoperated. Reoperation was more common in flap patients [15 vs. 8 %; p =
      0.001]. Overall morbidity was higher in flap closure [38 % flap vs. 31 % non
      flap; p < 0.001]. Dehiscence was higher for flap closure in the propensity score
      matched cohort [7 vs. 3 %; p < 0.001]. Flap closure was an independent predictor
      of dehiscence for both the overall and propensity score-matched groups.
      Dehiscence was not increased in patients who had neoadjuvant radiation [5.4 %
      flap vs. 2.6 % non-flap; p = 0.127]. CONCLUSIONS: This represents the largest
      study of flap vs. non-flap closure following APR and the first such study from a
      national database. Flap closure was independently associated with increased risk
      of wound dehiscence in both the overall and matched cohorts. This study
      highlights the challenge of wound complications following APR and provides real
      world generalizable data.

PMID- 26315015
TI  - Risk factors for anastomotic leak and postoperative morbidity and mortality after
      elective right colectomy for cancer: results from a prospective, multicentric
      study of 1102 patients.
AB  - BACKGROUND: Studies focused on postoperative outcome after oncologic right
      colectomy are lacking. The main objective was to determine pre-/intraoperative
      risk factors for anastomotic leak after elective right colon resection for
      cancer. Secondary objectives were to determine risk factors for postoperative
      morbidity and mortality. METHODS: Fifty-two hospitals participated in this
      prospective, observational study (September 2011-September 2012), including 1102
      patients that underwent elective right colectomy. Forty-two pre-/intraoperative
      variables, related to patient, tumor, surgical procedure, and hospital, were
      analyzed as potential independent risk factors for anastomotic leak and
      postoperative morbidity and mortality. RESULTS: Anastomotic leak was diagnosed in
      93 patients (8.4 %), and 72 (6.5 %) of them needed radiological or surgical
      intervention. Morbidity, mortality, and wound infection rates were 29.0, 2.6, and
      13.4 %, respectively. Preoperative serum protein concentration was the only
      independent risk factor for anastomotic leak (p < 0.0001, OR 0.6 per g/dL). When
      considering only clinically relevant anastomotic leaks, stapled technique (p =
      0.03, OR 2.1) and preoperative serum protein concentration (p = 0.004, OR 0.6
      g/dL) were identified as the only two independent risk factors. Age and
      preoperative serum albumin concentration resulted to be risk factors for
      postoperative mortality. Male gender, pulmonary or hepatic disease, and open
      surgical approach were identified as risk factors for postoperative morbidity,
      while male gender, obesity, intraoperative complication, and end-to-end
      anastomosis were risk factors for wound infection. CONCLUSIONS: Preoperative
      nutritional status and the stapled anastomotic technique were the only
      independent risk factors for clinically relevant anastomotic leak after elective
      right colectomy for cancer. Age and preoperative nutritional status determined
      the mortality risk, while laparoscopic approach reduced postoperative morbidity.

PMID- 26315017
TI  - An ecological study of sand flies (Diptera: Psychodidae) in the vicinity of
      Lencois Maranhenses National Park, Maranhao, Brazil.
AB  - BACKGROUND: The Lencois Maranhenses National Park, located in Maranhao, Brazil,
      is a region of exceptional beauty and a popular tourist destination. The
      adjoining area has suffered from the impact of human activity and, consequently,
      has experienced outbreaks of leishmaniasis. This study aimed to evaluate the
      composition, abundance, species richness and seasonal distribution of sand flies
      in the region and to determine the constancy of the insect population. METHODS:
      The survey was conducted at three sites located in the municipalities of
      Barreirinhas and Santo Amaro between September 2012 and August 2013. Sampling was
      performed monthly using automatic light traps installed 1.5 m above the soil
      adjacent to 13 randomly selected rural dwellings. At each site, one trap was
      placed in the peridomicile near to animal enclosures and another (extradomicile)
      at 500 m from the peridomicile. RESULTS: A total of 4,474 individual sand flies
      were collected over the year with the highest abundance recorded during the rainy
      season (December to June). Nine species were collected: L. whitmani, L.
      longipalpis, L. lenti, L. sordellii, L. evandroi, L. flaviscutellata, L.
      wellcomei, L. termitophila and L. intermedia. Although peridomiciliary and
      extradomiciliary environments presented similar species richness, the Shannon
      diversity index was significantly lower in the former (H' = 2.4) compared with
      the latter (H' = 4.98). Lutzomyia whitmani and L. longipalpis were the most
      abundant species and were classified as constant (constancy index, CI = 100%)
      along with L. lenti (CI = 58.3), L. evandroi (CI = 58.3) and L. sordellii (CI =
      66.7). The remaining four species presented CI values between 25 and 50% and were
      considered accessory. CONCLUSIONS: The present results confirm the present of L.
      whitmani and L. longipalpis in the peridomicile of houses in Lencois National
      Park. The abundance of these species could explain, respectively, the endemicity
      of cutaneous leishmaniasis and sporadic cases of visceral leishmaniasis in the
      study area. However, in the case of cutaneous leishmaniasis, the presence of
      other sand fly vectors (in addition to L. whitmani) cannot be neglected. Finally,
      this study emphasizes the need for a more effective and permanent supervision to
      control the expansion of these vectors and leishmaniasis outbreaks.

PMID- 26315018
TI  - ABC transporter PEN3/PDR8/ABCG36 interacts with calmodulin that, like PEN3, is
      required for Arabidopsis nonhost resistance.
AB  - Nonhost resistance (NHR) is the most prevalent form of plant immunity. In
      Arabidopsis, NHR requires membrane-localized ATP-binding cassette (ABC)
      transporter PENETRATION (PEN) 3. Upon perception of pathogen-associated molecular
      patterns, PEN3 becomes phosphorylated, suggestive of PEN3 regulation by post
      translational modification. Here, we investigated the PEN3 protein interaction
      network. We probed the Arabidopsis protein microarray AtPMA-5000 with the N
      terminal cytoplasmic domain of PEN3. Several of the proteins identified to
      interact with PEN3 in vitro represent cellular Ca(2+) sensors, including
      calmodulin (CaM) 3, CaM7 and several CaM-like proteins, pointing to the
      importance of Ca(2+) sensing to PEN3-mediated NHR. We demonstrated co
      localization of PEN3 and CaM7, and we confirmed PEN3-CaM interaction in vitro and
      in vivo by PEN3 pull-down with CaM Sepharose, CaM overlay assay and bimolecular
      fluorescence complementation. We also show that just like in pen3, NHR to the
      nonadapted fungal pathogens Phakopsora pachyrhizi and Blumeria graminis f.sp.
      hordei is compromised in the Arabidopsis cam7 and pen3 cam7 mutants. Our study
      discloses CaM7 as a PEN3-interacting protein crucial to Arabidopsis NHR and
      emphasizes the importance of Ca(2+) sensing to plant immunity. 

PMID- 26315019
TI  - Functional diversity of CTCFs is encoded in their binding motifs.
AB  - BACKGROUND: The CCCTC-binding factor (CTCF) has diverse regulatory functions.
      However, the definitive characteristics of the CTCF binding motif required for
      its functional diversity still remains elusive. RESULTS: Here, we describe a new
      motif discovery workflow by which we have identified three CTCF binding motif
      variations with highly divergent functionalities. Supported by transcriptomic,
      epigenomic and chromatin-interactomic data, we show that the functional diversity
      of the CTCF binding motifs is strongly associated with their GC content, CpG
      dinucleotide coverage and relative DNA methylation level at the 12th position of
      the motifs. Further analysis suggested that the co-localization of cohesin, the
      key factor in cohesion of sister chromatids, is negatively correlated with the
      CpG coverage and the relative DNA methylation level at the 12th position.
      Finally, we present evidences for a hypothetical model in which chromatin
      interactions between promoters and distal regulatory regions are likely mediated
      by CTCFs binding to sequences with high CpG. CONCLUSION: These results
      demonstrate the existence of definitive CTCF binding motifs corresponding to
      CTCF's diverse functions, and that the functional diversity of the motifs is
      strongly associated with genetic and epigenetic features at the 12th position of
      the motifs.

PMID- 26315021
TI  - Echocardiography in arrhythmogenic right ventricular dysplasia/cardiomyopathy:
      Can the technology survive in the era of cardiac magnetic resonance imaging?

PMID- 26315020
TI  - Reduced contextual effects on visual contrast perception in schizophrenia and
      bipolar affective disorder.
AB  - BACKGROUND: The salience of a visual stimulus is often reduced by nearby stimuli,
      an effect known as surround suppression of perceived contrast, which may help in
      locating the borders of an object. Weaker surround suppression has been observed
      in schizophrenia but it is unclear whether this abnormality is present in other
      mental disorders with similar symptomatology, or is evident in people with
      genetic liability for schizophrenia. METHOD: By examining surround suppression
      among subjects with schizophrenia or bipolar affective disorder, their unaffected
      biological relatives and healthy controls we sought to determine whether
      diminished surround suppression was specific to schizophrenia, and if subjects
      with a genetic risk for either disorder would show similar deficits. Measuring
      perceived contrast in different surround conditions also allowed us to
      investigate how this suppression depends on the similarity of target and
      surrounding stimuli. RESULTS: Surround suppression was weaker among schizophrenia
      patients regardless of surround configuration. Subjects with bipolar affective
      disorder showed an intermediate deficit, with stronger suppression than in
      schizophrenia but weaker than control subjects. Surround suppression was normal
      in relatives of both patient groups. Findings support a deficit in broadly tuned
      (rather than sharply orientation- or direction-selective) suppression mechanisms.
      CONCLUSIONS: Weak broadly tuned suppression during visual perception is evident
      in schizophrenia and bipolar affective disorder, consistent with impaired gain
      control related to the clinical expression of these conditions.

PMID- 26315022
TI  - The obesity paradox in heart failure needs scientific weight.

PMID- 26315023
TI  - Erectile dysfunction in atrial fibrillation: A risk factor for stroke or a
      reflection of stroke risk factors?

PMID- 26315024
TI  - Physicians' responses to computerized drug interaction alerts with password
      overrides.
AB  - BACKGROUND: Although evidence has suggested that computerized drug-drug
      interaction alert systems may reduce the occurrence of drug-drug interactions,
      the numerous reminders and alerts generated by such systems could represent an
      excessive burden for clinicians, resulting in a high override rate of not only
      unimportant, but also important alerts. METHODS: We analyzed physicians'
      responses to alerts of relative contraindications and contraindications for
      coadministration in a computerized drug-drug interaction alert system at Hokkaido
      University Hospital. In this system, the physician must enter a password to
      override an alert and continue an order. All of the drug-drug interaction alerts
      generated between December 2011 and November 2012 at Hokkaido University Hospital
      were included in this study. RESULTS: The system generated a total of 170 alerts
      of relative contraindications and contraindication for coadministration; 59 (34.7
      %) of the corresponding orders were cancelled after the alert was accepted, and
      111 (65.3 %) were overridden. The most frequent contraindication alert was for
      the combination of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors and
      fibrates. No incidents involving drug-drug interactions were reported among
      patients who were prescribed contraindicated drug pairs after an override.
      CONCLUSIONS: Although computerized drug-drug interaction alert systems that
      require password overrides appear useful for promoting medication safety, having
      to enter passwords to override alerts may represent an excessive burden for the
      prescribing physician. Therefore, both patient safety and physicians' workloads
      should be taken into consideration in future designs of computerized drug-drug
      interaction alert systems.

PMID- 26315025
TI  - Interview with Mario Muto, president of the 38th Annual Meeting of the ESNR.

PMID- 26315026
TI  - Reduced-dose CT protocol for the assessment of cerebral vasospasm.
AB  - INTRODUCTION: Despite the increased radiation dose, multimodal CT including
      noncontrast CT (NCT), CT angiography (CTA), and perfusion CT (PCT) remains a
      useful tool for the diagnosis of delayed cerebral ischemia (DCI) after aneurysmal
      subarachnoid hemorrhage (aSAH). The aim of this study was to assess the radiation
      dose and the image quality between a standard-dose and a reduced-dose multimodal
      CT protocol. METHODS: The study group consisted of 26 aSAH patients with a
      suspicion of DCI on clinical examination and transcranial doppler. Two different
      CT protocols were used: a standard-dose protocol (NCT 120 kV, 350 mAs; CTA 100
      kV, 250 mAs; PCT 80 kV, 200 mAs) from August 2011 to October 2013 (n = 13) and a
      reduced-dose protocol (NCT 100 kV, 400 mAs; CTA 100 kV, 220 mAs; PCT 80 kV, 180
      mAs) from November 2013 to May 2014 (n = 13). Dose-length product (DLP),
      effective dose, volume CT dose index (CTDI), signal-to-noise ratio (SNR),
      contrast-to-noise ratio (CNR), and overall image quality were determined for each
      examination. RESULTS: The overall image quality was judged as good or excellent
      in all cases. The reduced-dose protocol allowed a 15 % decrease in both the
      median total DLP (2438 vs 2898 mGy cm, p < 0.0001) and the effective dose as well
      as a significant decrease in median CTDI of 23, 31, and 10 % for NCT, CTA, and
      CTP, respectively. This dose reduction did not result in significant alteration
      of SNR (except for NCT) or CNR between groups. CONCLUSION: The present study
      showed that the reduced-dose multimodal CT protocol enabled a significant
      reduction of radiation dose without image quality impairment.

PMID- 26315027
TI  - A simple, high-throughput, colourimetric, field applicable loop-mediated
      isothermal amplification (HtLAMP) assay for malaria elimination.
AB  - BACKGROUND: To detect all malaria infections in elimination settings sensitive,
      high throughput and field deployable diagnostic tools are required. Loop-mediated
      isothermal amplification (LAMP) represents a possible field-applicable molecular
      diagnostic tool. However, current LAMP platforms are limited by their capacity
      for high throughput. METHODS: A high-throughput LAMP (HtLAMP) platform amplifying
      mitochondrial targets using a 96-well microtitre plate platform, processing 85
      samples and 11 controls, using hydroxynaphtholblue as a colourimetric indicator
      was optimized for the detection of malaria parasites. Objective confirmation of
      visually detectable colour change results was made using a spectrophotometer. A
      dilution series of laboratory-cultured 3D7 Plasmodium falciparum parasites was
      used to determine the limit of detection of the HtLAMP assay, using P. falciparum
      (HtLAMP-Pf) and Plasmodium genus (HtLAMP-Pg) primers, on whole blood and filter
      paper, and using different DNA extraction protocols. The diagnostic accuracy of
      HtLAMP was validated using clinical samples from Papua New Guinea, Malaysia,
      Ghana and The Gambia and its field applicability was evaluated in Kota Marudu
      district hospital, Sabah, Malaysia. RESULTS: The HtLAMP assay proved to be a
      simple method generating a visually-detectable blue and purple colour change that
      could be objectively confirmed in a spectrophotometer at a wavelength of 600 nm.
      When compared with PCR, overall HtLAMP-Pg had a sensitivity of 98 % (n = 260/266,
      95 % CI 95-99) and specificity 83 % (n = 15/18, 95 % CI 59-96). HtLAMP-Pf had a
      sensitivity of 97 % (n = 124/128, 95 % CI 92-99) and specificity of 96 % (n =
      151/157, 95 % CI 92-99). A validation study in a regional hospital laboratory
      demonstrated ease of performance and interpretation of the HtLAMP assay. HtLAMP
      Pf performed in this field setting had a sensitivity of 100 % (n = 17/17, 95 % CI
      80-100) and specificity of 95 % (n = 123/128, 95 % CI 90-98) compared with
      multiplex PCR. HtLAMP-Pf also performed well on filter paper samples from
      asymptomatic Ghanaian children with a sensitivity of 88 % (n = 23/25, 95 % CI 69
      97). CONCLUSION: This colourimetric HtLAMP assay holds much promise as a field
      applicable molecular diagnostic tool for the purpose of malaria elimination.

PMID- 26315029
TI  - Cyanidin induces apoptosis and differentiation in prostate cancer cells.
AB  - Several natural antioxidants, including anthocyanins, have been reported to have
      chemotherapeutic activity in vivo and in vitro. The aim of the present study was
      to delineate the anti-proliferative activity and the cytodifferentiation
      properties mediated by cyanidin-3-O-beta-glucopyranoside (C3G) treatment in the
      DU145 and LnCap human prostatic cancer cell lines. C3G produced anti
      proliferative effects through activation of caspase-3 and induction of p21
      protein expression. The reduced cell viability was associated with a clear
      increase of DNA fragmentation in both cell lines after C3G treatment. Since LnCap
      and DU145 exhibited differences in sensitivity to C3G treatment, the redox state
      of these cells was further investigated by estimating the levels of ROS and GSH.
      C3G antioxidant activity was confirmed only in DU145 cell line. Treatment with
      C3G increased the levels of tumor suppressor P75NGFR, indicating a possible role
      of C3G in the acquisition of a normal-like cell phenotype. Results reported in
      the present study demonstrate that C3G, the most abundant anthocyanin in diet,
      may represent a new approach and highly effective strategy in reducing
      carcinogenesis. C3G may be considered a new therapeutic agent with both anti
      proliferative and pro-differentiation properties.

PMID- 26315028
TI  - Gamma tocotrienol targets tyrosine phosphatase SHP2 in mammospheres resulting in
      cell death through RAS/ERK pathway.
AB  - BACKGROUND: There is increasing evidence supporting the concept of cancer stem
      cells (CSCs), which are responsible for the initiation, growth and metastasis of
      tumors. CSCs are thus considered the target for future cancer therapies. To
      achieve this goal, identifying potential therapeutic targets for CSCs is
      essential. METHODS: We used a natural product of vitamin E, gamma tocotrienol
      (gamma-T3), to treat mammospheres and spheres from colon and cervical cancers.
      Western blotting and real-time RT-PCR were employed to identify the gene and
      protein targets of gamma-T3 in mammospheres. RESULTS: We found that mammosphere
      growth was inhibited in a dose dependent manner, with total inhibition at high
      doses. Gamma-T3 also inhibited sphere growth in two other human epithelial
      cancers, colon and cervix. Our results suggested that both Src homology 2 domain
      containing phosphatase 1 (SHP1) and 2 (SHP2) were affected by gamma-T3 which was
      accompanied by a decrease in K- and H-Ras gene expression and phosphorylated ERK
      protein levels in a dose dependent way. In contrast, expression of self-renewal
      genes TGF-beta and LIF, as well as ESR signal pathways were not affected by the
      treatment. These results suggest that gamma-T3 specifically targets SHP2 and the
      RAS/ERK signaling pathway. CONCLUSIONS: SHP1 and SHP2 are potential therapeutic
      targets for breast CSCs and gamma-T3 is a promising natural drug for future
      breast cancer therapy.

PMID- 26315030
TI  - Minutisphaerales (Dothideomycetes, Ascomycota): a new order of freshwater
      ascomycetes including a new family, Minutisphaeraceae, and two new species from
      North Carolina, USA.
AB  - Minutisphaera is a recently established genus of freshwater Dothideomycetes
      characterized by small, globose to subglobose or apothecioid, erumpent to
      superficial, brown ascomata; fissitunicate, eight-spored, ovoid to obclavate
      asci; and 1-2-septate, clavate to broadly fusiform, hyaline to pale brown
      ascospores with or without a gelatinous sheath and filamentous appendages. The
      genus currently contains two species: M. fimbriatispora, the type species, and M.
      japonica. The higher-level phylogenetic relationship of Minutisphaera within the
      Dothideomycetes currently is unresolved. To establish the phylogenetic position
      of Minutisphaera within the Dothideomycetes and evaluate the phylogenetic
      affinities of newly collected Minutisphaera-like taxa, we sequenced three rDNA
      regions-18S, ITS1-5.8SITS2 (ITS) and 28S nuc rDNA, and a protein-coding gene,
      MCM7, for newly collected strains of Minutisphaera. Based on maximum likelihood
      and Bayesian analyses of a combined dataset (18S and 28S) composed of 167 taxa, a
      more refined dataset (28S and MCM7) comprising 52 taxa and a separate ITS
      dataset, and an examination of morphology, we describe and illustrate two new
      species of Minutisphaera. The Minutisphaera clade was strongly supported within
      the Dothideomycetes with likelihood and Bayesian statistics but did not share
      phylogenetic affinities with any existing taxonomic group within the
      Dothideomycetes. We therefore establish a new order, Minutisphaerales, and new
      family, Minutisphaeraceae, for this monophyletic clade of freshwater ascomycetes.
      Chemical analysis of the organic extract M. aspera (G427) resulted in isolation
      and characterization of five known secondary metabolites, of which four were
      dipeptides (1-4) and one an aromatic polyketide (5). Conversely, two aromatic
      polyketides (5, 6) were isolated and identified from the organic extract of M.
      parafimbriatispora (G156-4). The isolated compounds were tested for their
      antimicrobial activity against an array of bacteria and fungi. Compound 6 showed
      promising activity against Staphylococcus aureus and Mycobacterium smegmatis with
      minimal inhibitory concentration values of 30 and 60 MUg/mL, respectively. 

PMID- 26315032
TI  - Spatial Analysis Methods for Health Promotion and Education.
AB  - This article provides a review of spatial analysis methods for use in health
      promotion and education research and practice. Spatial analysis seeks to describe
      or make inference about variables with respect to the places they occur. This
      includes geographic differences, proximity issues, and access to resources. This
      is important for understanding how health outcomes differ from place to place;
      and in terms of understanding some of the environmental underpinnings of health
      outcomes data by placing it in context of geographic location. This article seeks
      to promote spatial analysis as a viable tool for health promotion and education
      research and practice. Four more commonly used spatial analysis techniques are
      described in-text. An illustrative example of motor vehicle collisions in a large
      metropolitan city is presented using these techniques. The techniques discussed
      are as follows: descriptive mapping, global spatial autocorrelation, cluster
      detection, and identification and spatial regression analysis. This article
      provides useful information for health promotion and education researchers and
      practitioners seeking to examine research questions from a spatial perspective.

PMID- 26315033
TI  - Sustaining a Pediatric Injury Prevention Program Through Educational Curriculum
      Dissemination.
AB  - Objective To examine the process of implementing, disseminating, and sustaining a
      pediatric pedestrian safety program in Miami-Dade County Public Schools as well
      as its utilization by education practitioners. Method A review of the
      programmatic phases, grant funding, publications, partnerships, curriculum
      completion data, teacher trainings, and 31 WalkSafe Curriculum Dissemination
      Surveys. Results The program has maintained partnerships with the school
      district, trauma centers, and other important stakeholders since the program's
      inception while grant funding has enabled the development, growth, and
      continuation of the program. Survey responses indicated the curriculum is easy to
      use and age-appropriate for learning, as well as identified sustainable measures
      for the future. Conclusion A multicomponent approach is essential for piloting,
      implementing, and sustaining an evidence-based pedestrian safety program in South
      Florida's public schools. Sustainable partnerships, policy through school board
      support, continued grant funding, community involvement, and evolving with the
      needs of schools and their communities are vital to sustaining program presence
      in the community.

PMID- 26315034
TI  - Translation of an Action Learning Collaborative Model Into a Community-Based
      Intervention to Promote Physical Activity and Healthy Eating.
AB  - Action Learning Collaboratives (ALCs), whereby teams apply quality improvement
      (QI) tools and methods, have successfully improved patient care delivery and
      outcomes. We adapted and tested the ALC model as a community-based obesity
      prevention intervention focused on physical activity and healthy eating. METHOD:
      The intervention used QI tools (e.g., progress monitoring) and team-based
      activities and was implemented in three communities through nine monthly
      meetings. To assess process and outcomes, we used a longitudinal repeated
      measures and mixed-methods triangulation approach with a quasi-experimental
      design including objective measures at three time points. RESULTS: Most of the 97
      participants were female (85.4%), White (93.8%), and non-Hispanic/Latino (95.9%).
      Average age was 52 years; 28.0% had annual household income of $20,000 or less;
      and mean body mass index was 35. Through mixed-effects models, we found some
      physical activity outcomes improved. Other outcomes did not significantly change.
      Although participants favorably viewed the QI tools, components of the QI process
      such as sharing goals and data on progress in teams and during meetings were
      limited. Participants' requests for more education or activities around physical
      activity and healthy eating, rather than progress monitoring and data sharing
      required for QI activities, challenged ALC model implementation. CONCLUSIONS: An
      ALC model for community-based obesity prevention may be more effective when
      applied to preexisting teams in community-based organizations.

PMID- 26315035
TI  - Collecting Comparative Data on Farmworker Housing and Health: Recommendations for
      Collecting Housing and Health Data Across Places and Time.
AB  - The substandard nature of the housing in which most farmworkers live has
      detrimental effects on their health, as well as on their children's health and
      development. However, little research has directly documented associations
      between farmworker housing and health; existing research is not always comparable
      due to differences in design and measurement. Comparative data can help determine
      actual causal links between housing characteristics and farmworker health and
      help to evaluate the efficacy of current housing policy. The goal of this paper
      is to provide guidelines promoting comparable research on farmworker housing and
      the association of this housing with health. This paper reviews general concepts
      relevant to measuring farmworker housing and health, issues that should be
      considered in designing farmworker housing and health research, data collection
      methods, and measures. It concludes with recommendations for a research agenda on
      farmworker housing and health. 

PMID- 26315036
TI  - Understanding the Role of Social Factors in Farmworker Housing and Health.
AB  - Differences in social advantage significantly influence health conditions and
      life expectancy within any population. Such factors reproduce historic class,
      race, and ethnic disparities in community success. Few populations in the United
      States face more social and economic disadvantage than farmworkers, and
      farmworker housing has significant potential to ameliorate or amplify the health
      impact of those disadvantages. Drawing on the limited direct research on
      farmworkers, and on additional research about poor, isolated, and immigrant
      societies, we propose four mechanisms through which housing can be expected to
      affect farmworker health: quality of social capital within farmworker
      communities, stress effects of poor housing situations, effects of housing on
      social support for healthy behaviors, and interactions among these factors,
      especially effects on children that can last for generations. Policy and planning
      definitions of "adequate" farmworker housing should take a more holistic view of
      housing needs to support specific social and community benefits in design
      decisions. 

PMID- 26315038
TI  - Commentary on: Power-Assisted Liposuction Mammaplasty (PALM): A New Technique for
      Breast Reduction.

PMID- 26315039
TI  - Male Nipple Reduction With a Simple Circular-Flap Technique.

PMID- 26315041
TI  - Patients Tested at a Laboratory for Hereditary Cancer Syndromes Show an Overlap
      for Multiple Syndromes in Their Personal and Familial Cancer Histories.
AB  - OBJECTIVE: Hereditary cancer testing guidelines are based on the premise that the
      common hereditary cancer syndromes have distinct, recognizable phenotypes.
      However, many syndromes present with overlapping cancers. The aim of this
      analysis was to identify the proportion of patients tested for Lynch syndrome
      (LS) or hereditary breast and ovarian cancer (HBOC) who met testing criteria for
      the other syndrome. METHOD: We analyzed a commercial laboratory database of
      patients tested for LS and HBOC in a clinical setting from 2006 to 2013. Patient
      cancer histories were analyzed using the 2012 NCCN criteria for LS and the 2013
      NCCN criteria for HBOC. RESULTS: In all, 7% of the patients tested for HBOC met
      criteria for LS testing. The majority of these patients had a family history of
      colorectal (30.9%) and/or endometrial cancer (22.7%). Conversely, 29.5% of the
      patients tested for LS met criteria for HBOC testing. In this group, 30.5% of the
      patients had a personal history of breast cancer, and 12.6% had a personal
      history of ovarian cancer. CONCLUSIONS: Our data demonstrate a substantial
      phenotypic overlap among patients for multiple common inherited cancer syndromes,
      which likely complicates diagnosis and test selection. This supports the value of
      multigene panels to identify pathogenic mutations in the absence of a clinically
      specific phenotype.

PMID- 26315040
TI  - In memoriam--Richard M. Elliott (1954-2015).

PMID- 26315042
TI  - Gene Variants Associated with Transient Neonatal Diabetes Mellitus in the Very
      Low Birth Weight Infant.
AB  - BACKGROUND: Transient and permanent neonatal diabetes mellitus (NDM), usually
      defined as diabetes diagnosed within the first 6 months of life, are rare
      conditions occurring in 1:90,000-260,000 live births. The origin of NDM is rarely
      related to type 1 diabetes, but rather to single gene defects. METHODS: Genetic
      analysis was performed using targeted parallel sequencing including 323 diabetes
      genes. Data were filtered by a locally developed program. RESULTS: A very low
      birth weight neonate born at 28 weeks postmenstrual age developed diabetes 13
      days after birth. The patient was treated with continuous subcutaneous insulin
      infusion. After 1 month, insulin treatment could be stopped. At 18 months of age,
      the child was normoglycemic and developing normally. Genetic analysis revealed a
      novel variant (p.Pro190Leu) in HNF4A, which is located in the ligand binding
      domain of the transcription factor, and the p.Glu23Lys variant in KCNJ11, which
      is associated with type 2 diabetes. CONCLUSION: Here, we describe a novel HNF4A
      variant associated with transient NDM in a premature infant. We hypothesize that
      the neonatal phenotype previously described in carriers of HNF4A mutations was
      modified by the additional variant in KCNJ11 and prematurity.

PMID- 26315043
TI  - Volume-Rendering Optical Coherence Tomography Angiography of Macular
      Telangiectasia Type 2.
AB  - PURPOSE: To evaluate the vascular structure of eyes with macular telangiectasia
      type 2 (MacTel2) using volume-rendered optical coherence tomography angiography
      (OCTA). DESIGN: Retrospective cross-sectional study. PARTICIPANTS: A total of 14
      consecutive patients (20 eyes) with MacTel2 who had a signal strength score >=55
      and could maintain fixation during the scan process. METHODS: The eyes were
      scanned using optical coherence tomography with split-spectrum amplitude
      decorrelation techniques to derive flow information. Data were extracted and used
      to create volume-rendered images of the retinal vasculature that could be rotated
      about 3 different axes for evaluation. MAIN OUTCOME MEASURES: Descriptive
      appraisal of the vascular abnormalities associated with MacTel2. RESULTS: Vessels
      posterior to the outer boundary of the deep retinal plexus were secondary to
      retinal thinning, vascular invasion, or a combination of both. These vessels had
      the same shape and distribution as the late staining seen during conventional
      fluorescein angiography. Lateral contraction in the temporal macula in 5 eyes
      created an appearance of vessels radiating from a central locus, which was the
      site of a right angle vein. Loss of macular tissue as part of the disease process
      led to a central amalgamation of the inner vascular plexus and the deep vascular
      plexus, which appeared to be in a state of decline. Subretinal neovascularization
      originated from the retinal circulation but involved not only the subretinal
      space but also could infiltrate the remaining, thinned, retina. CONCLUSIONS:
      Volume rendering of OCTA information preserves the 3-dimensional relationships
      among retinal vascular layers and provides opportunities to visualize retinal
      vascular abnormalities in unprecedented detail. The retinal vascular leakage and
      invasion in MacTel2 may arise as a consequence of loss of control with depletion
      of Muller cells and exposure of the remaining retinal vessels to the more hypoxic
      environment near the inner segments of the photoreceptors.

PMID- 26315044
TI  - Long-Term Outcomes of Trabeculectomy Augmented with Mitomycin C Undertaken within
      the First 2 Years of Life.
AB  - PURPOSE: To evaluate the long-term effectiveness and safety of mitomycin C (MMC)
      augmented trabeculectomy undertaken within the first 2 years of life for the
      surgical management of glaucoma. DESIGN: Retrospective, consecutive,
      noncomparative case series. PARTICIPANTS: All children who underwent MMC
      augmented trabeculectomy within 2 years of birth between May 2002 and November
      2012. METHODS: The medical records of 40 consecutive eyes of 26 children who
      underwent surgery by a single surgeon were reviewed. Data collected during
      routine clinical care were analyzed. MAIN OUTCOME MEASURES: Assessment of
      clinical outcomes included intraocular pressure (IOP), final visual acuity, bleb
      morphology, surgical complications (early and late), postoperative interventions,
      and further glaucoma surgery performed. Surgical success was defined as final IOP
      of 5 mmHg or more and of 21 mmHg or less, with anti-glaucoma medications
      (qualified success) and without (complete success), stable ocular dimensions and
      optic disc cupping, and no further glaucoma surgery (including needling) or loss
      of light perception. Surgical outcomes were evaluated using Kaplan-Meier life
      table analysis. RESULTS: Forty eyes of 26 children were studied over a mean
      follow-up period of 62.8 months. Most cases (80%) were of primary congenital
      glaucoma after failed goniotomy surgery. Cumulative probabilities of survival at
      1, 5, and 7 years were 78%, 67%, and 60%, respectively. Of eyes regarded as
      successful, 96% (25/26 eyes) had controlled IOP without topical medication and
      44% achieved visual acuity of 20/40 or better. In only 1 of the 40 eyes did a
      cystic avascular bleb develop, with all the other eyes being non-cystic in nature
      (diffuse and elevated or flat) at final follow-up. Sixty-four percent (9/14 eyes)
      of cases regarded as failures ultimately underwent glaucoma drainage device
      implantation. CONCLUSIONS: A contemporary pediatric trabeculectomy technique
      augmented with MMC is an effective procedure in the management of glaucoma within
      the first 2 years of life, as shown by the successful long-term outcomes and low
      incidence of sight-threatening complications. Trabeculectomy after failed
      goniotomy surgery or as a primary surgical intervention may offer a phakic infant
      with glaucoma an excellent opportunity to achieve long-term control of IOP
      without medications and may be associated with optimal visual outcomes.

PMID- 26315045
TI  - Cost-Effectiveness of Screening for Intermediate Age-Related Macular Degeneration
      during Diabetic Retinopathy Screening.
AB  - PURPOSE: To determine whether screening for age-related macular degeneration
      (AMD) during a diabetic retinopathy (DR) screening program would be cost
      effective in Hong Kong. DESIGN: We compared and evaluated the impacts of
      screening, grading, and vitamin treatment for intermediate AMD compared with no
      screening using a Markov model. It was based on the natural history of AMD in a
      cohort with a mean age of 62 years, followed up until 100 years of age or death.
      PARTICIPANTS: Subjects attending a DR screening program were recruited. METHOD: A
      cost-effectiveness analysis was undertaken from a public provider perspective. It
      included grading for AMD using the photographs obtained for DR screening and
      treatment with vitamin therapy for those with intermediate AMD. The measures of
      effectiveness were obtained largely from a local study, but the transition
      probabilities and utility values were from overseas data. Costs were all from
      local sources. The main assumptions and estimates were tested in sensitivity
      analyses. MAIN OUTCOME MEASURES: The outcome was cost per quality-adjusted life
      year (QALY) gained. Both costs and benefits were discounted at 3%. All costs are
      reported in United States dollars ($). RESULTS: The cost per QALY gained through
      screening for AMD and vitamin treatment for appropriate cases was $12,712 after
      discounting. This would be considered highly cost effective based on the World
      Health Organization's threshold of willingness to pay (WTP) for a QALY, that is,
      less than the annual per capita gross domestic product of $29,889. Because of
      uncertainty regarding the utility value for those with advanced AMD, we also
      tested an extreme, conservative value for utility under which screening remained
      cost effective. One-way sensitivity analyses revealed that, besides utility
      values, the cost per QALY was most sensitive to the progression rate from
      intermediate to advanced AMD. The cost-effectiveness acceptability curve showed a
      WTP for a QALY of $29,000 or more has a more than 86% probability of being cost
      effective compared with no screening. CONCLUSIONS: Our analysis demonstrated that
      AMD screening carried out simultaneously with DR screening for patients with
      diabetes would be cost effective in a Hong Kong public healthcare setting.

PMID- 26315046
TI  - The Health Impact of Intensive and Nonintensive Grandchild Care in Europe: New
      Evidence From SHARE.
AB  - OBJECTIVES: Grandparents are an important source of childcare. However, caring
      for grandchildren may affect grandparents' health in both positive and negative
      ways. Our study examines the association between grandparental childcare and
      grandparents' health at 2- and 4-year follow-up. METHOD: Our study is based on
      grandparents aged 50 and older from Waves 1-4 of the Survey of Health, Ageing and
      Retirement in Europe (SHARE). Using multivariate analyses, we investigated
      associations between intensive and nonintensive grandparental childcare at Wave 2
      and subsequent health (self-rated health, depressive symptoms, and disability)
      controlling for covariates and health at baseline. Associations between changes
      over time in grandparental childcare and health at follow-up were also explored.
      Multiple imputation techniques and sensitivity analyses were undertaken to
      investigate possible biases arising from sample attrition. RESULTS: Grandparents
      looking after grandchildren, whether intensively or nonintensively, experienced
      some health benefits. Associations strengthened when attrition was accounted for,
      particularly if it is assumed that those who dropped out of the study were in
      poor health. DISCUSSION: Our results show better health among grandparents who
      provided grandchild care in the European countries studied. These results are
      important given the widespread provision of grandchild care in Europe.

PMID- 26315047
TI  - Prenatal Therapy Improves the Survival of Premature Infants with Congenital
      Chylothorax.
AB  - BACKGROUND: Chylothorax is a rare condition among neonates, although it is
      considered clinically significant, as it is difficult to manage in these
      patients. In addition, the course of chylothorax varies widely. Therefore, we
      aimed to elucidate the clinical features and effect of prenatal therapy on the
      prognosis of congenital chylothorax in neonates. METHODS: We retrospectively
      reviewed the medical records of all infants with congenital chylothorax who were
      admitted to National Taiwan University Hospital, Taipei, Taiwan between January
      2000 and December 2012. Their demographic characteristics, as well as their
      antenatal, perinatal, and postnatal information, were collected for our analysis
      of the mortality risk. RESULTS: We found 29 infants who were diagnosed with
      congenital chylothorax during the study period. The median gestational age at
      birth was 34 weeks (range, 28-41 weeks), and 71% of the infants presented with
      hydrops fetalis. Most cases of congenital chylothorax were bilateral (bilateral:
      86.2%, unilateral: 13.79%), and the overall survival rate was 59.6%. Among the
      cases with a prenatal diagnosis at <= 34 weeks of gestation, infants who received
      prenatal therapy had a significantly higher survival rate, compared to infants
      who did not receive prenatal therapy (76.9% vs. 11%, respectively; p = 0.008).
      CONCLUSION: We found that infants whose chylothorax was diagnosed <= 34 weeks of
      gestation, and who subsequently received prenatal therapy, experienced a better
      perinatal condition and exhibited improved postnatal outcomes.

PMID- 26315050
TI  - Complications and their management in endometriosis surgery.
AB  - Endometriosis is a common chronic disease mostly seen in young women.
      Endometriosis surgery may be considered as rather challenging in gynecology. In
      this article, we tried to emphasize on basic concepts of endometriosis surgery,
      the best surgical method that should be applied and the complications and the
      management of the complications. 

PMID- 26315048
TI  - Docosahexaenoic acid attenuates Western diet-induced hepatic fibrosis in Ldlr-/-
      mice by targeting the TGFbeta-Smad3 pathway.
AB  - DHA (22:6,omega3), but not EPA (20:5,omega3), attenuates Western diet (WD)
      induced hepatic fibrosis in a Ldlr(-/-) mouse model of nonalcoholic
      steatohepatitis. We examined the molecular basis for the differential effect of
      dietary EPA and DHA on WD-induced hepatic fibrosis. DHA was more effective than
      EPA at preventing WD-induced effects on hepatic transcripts linked to fibrosis,
      including collagen 1A1 (Col1A1), transforming growth factor-beta (TGFbeta)
      signaling and proteins involved in remodeling the extracellular matrix, including
      metalloproteases, tissue inhibitors of metalloproteases, and lysyl oxidase
      subtypes. Examination of the TGFbeta pathway showed that mice fed the WD
      supplemented with either olive oil or EPA had a significant (>=2.5-fold) increase
      in hepatic nuclear abundance of phospho-mothers against decapentaplegic homolog
      (Smad)3 when compared with mice fed the reference diet (RD); Smad3 is a key
      regulator of Col1A1 expression in stellate cells. In contrast, mice fed the WD
      supplemented with DHA had no increase in phospho-Smad3 when compared with mice
      fed the RD. Changes in hepatic phospho-Smad3 nuclear content correlated with
      proCol1A1 mRNA and protein abundance. Pretreatment of human LX2 stellate cells
      with DHA, but not other unsaturated fatty acids, blocked TGFbeta1-mediated
      induction of Col1A1. In conclusion, DHA attenuates WD-induced fibrosis by
      targeting the TGFbeta-Smad3-Col1A1 pathway in stellate cells. 

PMID- 26315049
TI  - Contribution of Nrf2 to Atherogenic Phenotype Switching of Coronary Arterial
      Smooth Muscle Cells Lacking CD38 Gene.
AB  - BACKGROUND/AIMS: Recent studies have indicated that CD38 gene deficiency results
      in dedifferentiation or transdifferentiation of arterial smooth muscle cells upon
      atherogenic stimulations. However, the molecular mechanisms mediating this
      vascular smooth muscle (SMC) phenotypic switching remain unknown. Methods &
      RESULTS: In the present study, we first characterized the phenotypic change in
      the primary cultures of coronary arterial myocytes (CAMs) from CD38-/- mice. It
      was shown that CD38 deficiency decreased the expression of contractile marker
      calponin, SM22alpha and alpha-SMA but increased the expression of SMC
      dedifferentiation marker, vimentin, which was accompanied by enhanced cell
      proliferation. This phenotypic change in CD38-/- CAMs was enhanced by 7
      ketocholesterol (7-Ket), an atherogenic stimulus. We further found that the CD38
      deficiency decreased the expression and activity of nuclear factor E2-related
      factor 2 (Nrf2), a basic leucine zipper (bZIP) transcription factor sensitive to
      redox regulation. Similar to CD38 deletion, Nrf2 gene silencing increased CAM
      dedifferentiation upon 7-Ket stimulation. In contrast, the overexpression of Nrf2
      gene abolished 7-Ket-induced dedifferentiation in CD38-/- CAMs. Given the
      sensitivity of Nrf2 to oxidative stress, we determined the role of redox
      signaling in the regulation of Nrf2 expression and activity associated with CD38
      effect in CAM phenotype changes. It was demonstrated that in CD38-/- CAMs, 7-Ket
      failed to stimulate the production of O2-., while in CD38+/+ CAMs 7-Ket induced
      marked O2-. production and enhancement of Nrf2 activity, which was substantially
      attenuated by NOX4 gene silencing. Finally, we demonstrated that 7-Ket-induced
      and NOX4-dependent O2-. production was inhibited by 8-Br-cADPR, an antagonist of
      cADPR or NED-19, an antagonist of NAADP as product of CD38 ADP-ribosylcyclase,
      which significantly inhibited the level of cytosolic Ca2+ and the activation of
      Nrf2 under 7-Ket. CONCLUSION: Taken together, these results suggest that CD38
      activity is required for 7-Ket-induced Ca2+ and consequently O2-. production in
      CAMs, which increases Nrf2 activity to maintain their differentiated status. When
      CD38 gene expression and function are deficient, the Nrf2 activity is suppressed,
      thereby leading to phenotypic switching of CAMs.

PMID- 26315051
TI  - Dynamic antimullerian hormone levels during controlled ovarian hyperstimulation
      predict in vitro fertilization response and pregnancy outcomes.
AB  - OBJECTIVE: To evaluate the patterns of change in serum antimullerian hormone
      (AMH) during controlled ovarian hyperstimulation (COH) and their relation to
      concurrent response and in vitro fertilization (IVF) pregnancy outcomes. DESIGN:
      Prospective cohort study. SETTING: Academic medical center. PATIENT(S): A total
      of 113 consecutive fresh IVF embryo transfer cycles from September 1, 2012
      through January 1, 2013. INTERVENTION(S): Serial serum AMH measurements were
      analyzed on each day that serum estradiol (E2) was drawn during COH. MAIN OUTCOME
      MEASURE(S): Relationship between the rate of COH AMH change [Delta ng/mL per day]
      (stratified into tertiles), and ovarian response, and pregnancy outcomes.
      RESULT(S): During COH, AMH declined. Age and ovarian reserve testing were
      associated with the rate of AMH decline (RAD). Women with intermediate and
      minimal RAD had statistically significantly fewer follicles >= 12 mm, lower peak
      serum E2, fewer oocytes, and inferior early embryo development compared with
      women with the greatest RAD. Compared with patients with the lowest RAD, clinical
      pregnancy was more likely in patients with the greatest RAD in the total
      population (adjusted odds ratio 3.51; 95% confidence interval, 1.03, 11.94) and
      among patients older than 35 years (adjusted odds ratio 6.95; 95% confidence
      interval, 1.09, 44.1). CONCLUSION(S): The rate of COH AMH decline was associated
      with ovarian reserve testing, oocyte yield, embryo progression, and clinical
      pregnancy rates, particularly in women older than 35 years. These results suggest
      that dynamic AMH levels may provide a novel intracycle approach to predict
      response and treatment outcomes after IVF.

PMID- 26315052
TI  - Part One: For the Motion. An Endovascular First Strategy is the Optimal Approach
      for Treating Acute Mesenteric Ischemia.

PMID- 26315053
TI  - Part Two: Against the Motion. An Endovascular First Strategy is not the Optimal
      Approach for Treating Acute Mesenteric Ischemia.

PMID- 26315054
TI  - Arthroscopic Talocalcaneal Coalition Resection in Children.
AB  - PURPOSE: To present the technique and outcomes of arthroscopic talocalcaneal
      coalition (TCC) resection in pediatric patients. METHODS: We performed a
      prospective study of 16 consecutive feet with persistent symptomatic TCCs in 15
      children. The mean age was 11.8 years (range, 8 to 15 years), and the mean follow
      up period was 28 months (range, 12 to 44 months). A posterior arthroscopic TCC
      resection was performed. The plantar footprint, subtalar motion, pain, and the
      American Orthopaedic Foot & Ankle Society Ankle-Hindfoot scale score were
      evaluated preoperatively and postoperatively. Preoperative computed tomography
      (CT) scans were used to classify the coalition according to the Rozansky
      classification, to measure the percentage of involvement of the surface area, and
      to determine the degree of hindfoot valgus. Postoperative CT scans at 1 year (n =
      15) and 3 years (n = 5) were used to assess recurrences. Patient satisfaction was
      also evaluated. RESULTS: The TCC distribution according to the Rozansky
      classification was type I in 7 cases, type II in 3, type III in 3, and type IV in
      3. In all cases the arthroscopic approach enabled complete coalition resection.
      All patients increased by at least 1 stage in the footprint classification and
      showed clinical subtalar mobility after surgery. All patients showed a
      statistically significant improvement in pain after surgery except for 1 patient
      in whom complex regional pain syndrome developed (P < .001). The mean American
      Orthopaedic Foot & Ankle Society score was 56.8 (range, 45 to 62) preoperatively
      versus 90.9 (range, 36 to 100) postoperatively, showing a statistically
      significant increase (P < .001). Preoperative CT scans showed that all TCCs
      involved the medial subtalar joint facet, with mean involvement of 40.8% of the
      articular surface. All postoperative CT scans showed complete synostosis
      resections with no recurrences at final follow-up. At final follow-up, all
      patients were either satisfied (n = 4 [27%]) or extremely satisfied (n = 10
      [67%]) with the outcome, except the 1 patient (7%) in whom complex regional pain
      syndrome developed. CONCLUSIONS: Arthroscopic TCC resection provides good
      outcomes (symptom relief and restoration of subtalar motion), with no recurrence
      of the coalition. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 26315055
TI  - Asymmetry in Femoral Tunnel Socket Length During Anterior Cruciate Ligament
      Reconstruction With Transportal, Outside-In, and Modified Transtibial Techniques.
AB  - PURPOSE: To investigate the mismatch between the length at the center and the
      length on the shortest and longest peripheral sides of the femoral tunnel socket,
      reamed with the transportal (TP), outside-in (OI), and modified transtibial (TT)
      techniques, in anterior cruciate ligament (ACL) reconstruction. METHODS: Femoral
      tunnel drilling was simulated on 3-dimensional bone models from 40 subjects. The
      tunnel directions used with the TP, OI, and modified TT techniques were
      previously described. By use of the resulting angle, a femoral tunnel socket of 9
      mm in diameter was drilled from the center of the femoral ACL insertion. The
      virtual femoral tunnel was extracted, and the length mismatch was measured
      between the center and the shortest and longest peripheral sides of the tunnel
      socket. RESULTS: The mean socket length mismatch between the center and the
      shortest peripheral part of the femoral tunnel socket was 4.2 +/- 0.9 mm with the
      TP technique, 5.2 +/- 1.3 mm with the OI technique, and 3.2 +/- 0.8 mm with the
      modified TT technique. The mean socket length mismatch between the center and the
      longest peripheral part of the femoral tunnel socket was 3.5 +/- 0.9 mm with the
      TP technique, 4.8 +/- 1.5 mm with the OI technique, and 3.3 +/- 1.2 mm with the
      modified TT technique. The length mismatch was significantly higher when the
      tunnel socket was created by the OI technique (P < .01). CONCLUSIONS: A length
      mismatch with the tunnel socket exists after reaming with either the TP, OI, or
      modified TT technique. In particular, there was a significant increase in length
      mismatch when the tunnel socket was created by the OI technique, and the length
      mismatch would easily become greater than 5 mm. The surgeon should recognize this
      mismatch when it is created and measure the femoral tunnel socket. CLINICAL
      RELEVANCE: In anatomic ACL reconstruction, a mismatch between the length at the
      center and the length at periphery of the femoral tunnel socket occurs, and this
      is increased particularly when using the OI technique. The discrepancy in tunnel
      length between its center and its periphery could cause an overestimation of the
      tunnel length that could result in an error in length during graft preparation.

PMID- 26315056
TI  - Outcomes After Labral Repair in Patients With Femoroacetabular Impingement and
      Borderline Dysplasia.
AB  - PURPOSE: To determine outcomes after labral repair in patients with borderline
      dysplasia and femoroacetabular impingement (FAI). METHODS: Patients with
      dysplasia treated between June 2005 and March 2009 were identified. The study
      included only patients aged 18 years or older (mean, 35 years; range, 18 to 69
      years) whose affected hip had a Wiberg center-edge angle of 20 degrees  to 25
      degrees  and who underwent primary hip arthroscopy performed by the senior
      author. RESULTS: One hundred two hips (100 patients, comprising 50 women and 50
      men) underwent hip arthroscopy with labral repair with correction of FAI and
      capsular closure. Five hips were converted to total hip arthroplasty, and 7
      required revision arthroscopy. Of 95 patients (representing 100 hips, 5 of which
      underwent total hip arthroplasty), 80 were monitored for a minimum of 2 years. At
      a mean follow-up point of 40 months, the preoperative modified Harris Hip Score
      had improved from a mean of 63.5 points (range, 20 to 98 points) to a mean of
      84.9 points (range, 45 to 100 points) by the latest follow-up (P < .001). The
      mean score on the Western Ontario and McMaster Universities Arthritis Index
      improved from 25.3 (range, 0 to 60) to 9.7 (range, 0 to 59) (P < .001). The 12
      Item Short Form Health Survey Physical Component Summary score also significantly
      improved (from 42.5 to 50.9, P = .001), whereas the 12-Item Short Form Health
      Survey Mental Health Component Summary score showed an insignificant improvement
      (from 52.4 to 54.1). CONCLUSIONS: This study showed that FAI and labral pathology
      can be successfully managed using hip arthroscopy, with capsular management, in
      patients with borderline dysplasia. Patients showed significant improvements in
      outcomes and high levels of satisfaction after hip arthroscopy. The need for
      subsequent procedures was similar to that in patients with just FAI and labral
      repair. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 26315057
TI  - Good medical practices in the use of antibiotic prophylaxis in a surgery ward:
      Results of a 2013 Apulian study.
AB  - This study describes the changes in the performance of health care workers
      regarding the control of health care-associated infection in a surgical ward of
      University Hospital Policlinico, Bari, Italy, before and after a training program
      and adoption of bundles on antibiotic therapy. There were 194 patients recruited
      (pre: n = 98; post: n = 96), of which 149 (76.8%) had undergone surgery. We
      documented a change in the proportions of patients who received in-ward
      prophylactic antibiotics (from 46/98 to 22/96, P < .05), surgical patients
      undergoing antibiotic prophylaxis in the operating room (from 18/64 to 36/85, P <
      .05), and average duration of prophylaxis (from 5.9 +/- 4.9 to 2.9 +/- 2.7 days,
      P < .0001). Results confirmed correspondence between the intervention and results
      recorded. 

PMID- 26315058
TI  - Effectiveness of a hydrogen peroxide spray for decontamination of soft surfaces
      in hospitals.
AB  - In a survey of two hospitals, soft surfaces were commonly present in inpatient
      and outpatient settings, and contamination with health care-associated pathogens
      was frequently detected. An improved hydrogen peroxide cleaner disinfectant was
      effective for decontamination of soft surfaces when applied as a spray with no
      mechanical wiping. 

PMID- 26315059
TI  - Antimicrobial stewardship to optimize the use of antimicrobials for surgical
      prophylaxis in Egypt: A multicenter pilot intervention study.
AB  - OBJECTIVE: To measure the impact of an antimicrobial stewardship (AMS) program on
      the use of antibiotics for surgical prophylaxis at acute care hospitals in Egypt.
      METHODS: This was a before-and-after intervention study conducted in 5 tertiary,
      acute-care surgical hospitals. The baseline, intervention, and follow-up periods
      were 3, 6, and 3 months, respectively. The impact of the intervention was
      measured by preintervention and postintervention surveys for surgical patients
      with clean and clean-contaminated wounds. Information was collected on
      demographic characteristics and antibiotic use. The intervention focused mainly
      on educating surgical staff on the optimal timing and duration of antibiotics
      used for surgical prophylaxis. Only 3 hospitals identified a surgeon to audit
      antibiotic surgical prescriptions. The primary outcome measures were the
      percentages of surgical patients receiving optimal timing and duration of
      surgical prophylaxis. RESULTS: Data were collected for 745 patients before the
      intervention and for 558 patients after the intervention. The optimal timing of
      the first dose improved significantly in 3 hospitals, increasing from 6.7% to
      38.7% (P < .01), from 2.6% to 15.2% (P < .01), and from 0% to 11% (P < .01). All
      hospitals showed a significant rise in the optimal duration of surgical
      prophylaxis, with an overall increase of 3%-28% (P < .01). Days of therapy per
      1000 patient-days were decreased significantly in hospitals A, B, C, and D, with
      no change in hospital E. CONCLUSIONS: An AMS program focusing on education
      supported by auditing and feedback can have a significant impact on optimizing
      antibiotic use in surgical prophylaxis practices.

PMID- 26315060
TI  - Health care-associated infections surveillance in an intensive care unit of a
      university hospital in China, 2010-2014: Findings of International Nosocomial
      Infection Control Consortium.
AB  - Using a standardized methodology by the National Nosocomial Infection
      Surveillance System, a continuous health care-associated infections (HAIs)
      surveillance was conducted in our mixed intensive care unit at a Chinese teaching
      hospital. During the study period (2010-2014), 4,013 patients were hospitalized
      for 32,924 bed days and acquired 427 HAIs (482 HAI events), with an overall rate
      of 10.64% and 14.640 HAIs per 1,000 bed days. Ventilator-associated pneumonia was
      the most common device-associated health care-acquired infection, with an
      incidence rate of 19.561 per 1,000 mechanical ventilator days. 

PMID- 26315061
TI  - Retrospective analysis of hospital-acquired linezolid-nonsusceptible enterococci
      infection in Chongqing, China, 2011-2014.
AB  - BACKGROUND: Linezolid-nonsusceptible enterococci (LNSE) is an increasingly
      emerging multidrug-resistant pathogen, and the caused nosocomial infections are
      difficult to manage. However, data on the host-related risk factors and clinical
      outcomes for LNSE infection are poorly characterized. METHODS: A retrospective
      case-case-control study of risk factors and clinical outcomes of hospitalized
      patients with LNSE infection during the period 2011-2014 was conducted in a
      teaching hospital in Chongqing, China. Case patients with LNSE and those with
      linezolid-susceptible enterococci (LSE) and controls with no enterococcal
      infection were compared at a ratio of 1:1:4. Two parallel multivariate logistic
      regression models were used to evaluate independent predictors for acquiring LNSE
      and LSE, respectively. RESULTS: Forty-four LNSE cases, 44 LSE cases, and 176
      uninfected controls were analyzed. Multivariable analysis indicated that
      transferring from another hospital (odds ratio [OR], 3.57; 95% confidence
      interval [CI], 1.58-8.09), peripheral vascular disease (OR, 4.36; 95% CI, 1.64
      11.60), and exposure to cephalosporins (OR, 4.24; 95% CI, 1.85-9.71) were unique
      independent predictors for acquiring LNSE. Gallbladder disease (OR, 3.64; 95% CI,
      1.36-9.74) was independently associated with LSE acquisition. Polymicrobial
      infection was the only factor identified in both LNSE and LSE groups compared
      with controls; however, no statistical significance was observed in in-hospital
      mortality. CONCLUSION: Timely control efforts and appropriate antibiotic
      stewardship programs are necessary to effectively reduce the burden of LNSE
      infections among high-risk patients.

PMID- 26315063
TI  - Diagnostic Criteria as Separate From Classification Criteria: A Perpetual Motion
      Machine? Comment on the Article by Aggarwal et al.

PMID- 26315062
TI  - Coumarin derivatives from Ainsliaea fragrans and their anticoagulant activity.
AB  - Coumarin derivatives are an important class of C6-C3 plant metabolites that show
      a variety of bioactivities. Currently, most clinical anticoagulant agents are
      coumarins, such as warfarin, dicoumarol and acenocoumarol, and patients taking
      these drugs must be monitored for adverse reactions. In a search for safe and
      effective anticoagulant compounds from Chinese herbal medicine, a screening
      procedure on the whole plant of Ainsliaea fragrans was performed. The
      phytochemical investigation of this plant afforded five new coumarin derivatives,
      including a pair of natural 4-hydroxycoumarin enantiomers (1), a pair of coumarin
      enantiomers with a rare polycyclic pyrano[3-2c] carbon skeleton (2) and a 7
      hydroxycoumarin derivative (3), together with 5 known biogenetically related
      compounds (4-8). Enantioseparation of 1 and 2 produced optically pure compounds
      1a, 1b, 2a and 2b. The absolute configurations of the new compounds were
      confirmed by single-crystal X-ray diffraction analysis. In addition, we evaluated
      the anticoagulant activity of all isolates via activated partial thromboplastin
      time (APTT), thrombin time (TT) and prothrombin time (PT) assays in vitro and in
      vivo. Of note, compound 3 displayed potent anticoagulant activity and no
      significant hepatic or renal toxicity, which could make it a promising agent for
      further preclinical evaluation for preventing abnormal blood clotting. 

PMID- 26315064
TI  - Whole genome PCR scanning (WGPS) of Coxiella burnetii strains from ruminants.
AB  - Coxiella burnetii is the causative agent of Q fever, a zoonosis that spreads from
      ruminants to humans via the inhalation of aerosols contaminated by livestock's
      birth products. This study aimed to compare the genomes of strains isolated from
      ruminants by "Whole Genome PCR Scanning (WGPS)" in order to identify genomic
      differences. C. burnetii isolated from different ruminant hosts were compared to
      the Nine Mile reference strain using WGPS. The identified genomic regions of
      differences (RDs) were confirmed by sequencing. A set of 219 primers for
      amplification of 10 kbp segments covering the entire genome was obtained. The
      analyses revealed the presence of: i) conserved genomic regions, ii) genomic
      polymorphism including insertions and deletions and iii) amplification failures
      in some cases as well. WGPS, a descriptive approach, allowed the identification
      and localization of divergent genetic loci from various strains of C. burnetii
      which consisted of deletions, insertions and maybe genomic rearrangements. It
      also substantiates the role played by the IS1111 element in the genomic
      plasticity of C. burnetii. We believe that this approach could be combined with
      new sequencing technologies, as a selective/directed sequencing approach,
      particularly when repeated sequences are present in the analysed genomes. 

PMID- 26315065
TI  - Prediction of solvent-induced morphological changes of polyelectrolyte diblock
      copolymer micelles.
AB  - Self-assembly processes of polyelectrolyte block copolymers are ubiquitous in
      industrial and biological processes; understanding their physical properties can
      also provide insights into the design of polyelectrolyte materials with novel and
      tailored properties. Here, we report systematic analysis on how the ionic
      strength of the solvent and the length of the polyelectrolyte block affect the
      self-assembly and morphology of the polyelectrolyte block copolymer materials by
      constructing a salt-dependent morphological phase diagram using an implicit
      solvent ionic strength (ISIS) method for dissipative particle dynamics (DPD)
      simulations. This diagram permits the determination of the conditions for the
      morphological transition into a specific shape, namely vesicles or lamellar
      aggregates, wormlike/cylindrical micelles, and spherical micelles. The scaling
      behavior for the size of spherical micelles is predicted, in terms of radius of
      gyration (R(g,m)) and thickness of corona (Hcorona), as a function of solvent
      ionic strength (c(s)) and polyelectrolyte length (NA), which are R(g,m) ~ c(s)(
      0.06)N(A)(0.54) and Hcorona ~ c(s)(-0.11)N(A)(0.75). The simulation results were
      corroborated through AFM and static light scattering measurements on the example
      of the self-assembly of monodisperse, single-stranded DNA block-copolynucleotides
      (polyT50-b-F-dUTP). Overall, we were able to predict the salt-responsive
      morphology of polyelectrolyte materials in aqueous solution and show that a
      spherical-cylindrical-lamellar change in morphology can be obtained through an
      increase in solvent ionic strength or a decrease of polyelectrolyte length.

PMID- 26315066
TI  - Reversible adapting layer produces robust single-crystal electrocatalyst for
      oxygen evolution.
AB  - Electrochemically converting water into oxygen/hydrogen gas is ideal for high
      density renewable energy storage in which robust electrocatalysts for efficient
      oxygen evolution play crucial roles. To date, however, electrocatalysts with long
      term stability have remained elusive. Here we report that single-crystal Co3O4
      nanocube underlay with a thin CoO layer results in a high-performance and high
      stability electrocatalyst in oxygen evolution reaction. An in situ X-ray
      diffraction method is developed to observe a strong correlation between the
      initialization of the oxygen evolution and the formation of active metal
      oxyhydroxide phase. The lattice of skin layer adapts to the structure of the
      active phase, which enables a reversible facile structural change that
      facilitates the chemical reactions without breaking the scaffold of the
      electrocatalysts. The single-crystal nanocube electrode exhibits stable,
      continuous oxygen evolution for >1,000 h. This robust stability is attributed to
      the complementary nature of defect-free single-crystal electrocatalyst and the
      reversible adapting layer. 

PMID- 26315067
TI  - Construction and Validation of the Vestibular Screening Tool for Use in the
      Emergency Department and Acute Hospital Setting.
AB  - OBJECTIVES: To construct a new vestibular screening tool to identify likely
      vestibular disorders and guide referral of dizzy patients presenting to hospital
      and to test the vestibular screening tool for construct and discriminative
      validity and reliability of physiotherapy assessors. DESIGN: Methodologic study.
      SETTING: Emergency and acute hospital wards of a metropolitan hospital.
      PARTICIPANTS: Adults (N=114) presenting to hospital with dizziness (mean age,
      67.36+/-14.88y; 57% women). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES:
      Three vestibular screening tools (3, 4, and 5 items) were investigated.
      Physiotherapy vestibular diagnostic tests categorized patients as vestibular or
      nonvestibular patients. Subsets of patients were assessed twice by 2
      physiotherapists (n=20) and twice by the same physiotherapist (n=30). RESULTS:
      Each of the vestibular screening tools had a good fit to the Rasch measurement
      model. Factor analysis demonstrated individual items loaded across 1 factor,
      confirming unidimensionality of the 3 vestibular screening tools, and Cronbach
      alpha determined internal consistency. The 4-item vestibular screening tool had
      the greatest area under the curve using receiver operator curve analysis (.894),
      with highest sensitivity (83%) and specificity (84%) for identifying vestibular
      disorders (cutoff value >=4/8). Sensitivity of the 3- and 5-item versions was
      lower than the 4-item vestibular screening tool (80%). The 4-item vestibular
      screening tool scores showed high intrarater (kappa item scores, .831-1;
      intraclass correlation coefficient [ICC] total, .988) and interrater (kappa item
      scores, .578-.921; ICC total, .878) reliability. CONCLUSIONS: The 4-item
      vestibular screening tool is a reliable, valid tool for screening dizzy patients
      presenting to hospital, with unidimensional construct validity, high sensitivity,
      and specificity for identifying likely vestibular disorders. The vestibular
      screening tool could be used clinically to streamline referrals of dizzy patients
      to vestibular clinics.

PMID- 26315068
TI  - Longitudinal Gliding of the Median Nerve in the Carpal Tunnel: Ultrasound
      Cadaveric Evaluation of Conventional and Novel Concepts of Nerve Mobilization.
AB  - OBJECTIVE: To evaluate median nerve excursion during conventional nerve gliding
      exercises and newly developed exercises, primarily comprising abduction and
      adduction of the fingers. DESIGN: Descriptive study. SETTING: Anatomical
      dissection facility. CADAVERS: Random sample of upper extremities of fresh whole
      body human cadavers (N=18). Cadavers with neuromuscular diseases in the medical
      record or anatomic variations were excluded. INTERVENTION: Conventional and new
      nerve gliding exercises. MAIN OUTCOME MEASURES: Distances between markers applied
      into the nerve and markers in the periosteum were visualized with ultrasound and
      measured. Comparisons of nerve excursions between different exercises were
      performed. RESULTS: Conventional exercises led to substantial nerve gliding
      proximal to the carpal tunnel and between the head of the pronator teres (12 and
      13.8mm, respectively), but it led to far less in the carpal tunnel (6.6mm). With
      our novel exercises, we achieved nerve gliding in the carpal tunnel of 13.8mm. No
      substantial marker movement could be detected during lateral flexion of the
      cervical spine. CONCLUSIONS: Although conventional nerve gliding exercises only
      lead to minimal nerve excursions in the carpal tunnel, our novel exercises with
      the abduction and adduction of the fingers result in substantial longitudinal
      gliding throughout the arm. Clinical trials will have to deliver the clinical
      evidence.

PMID- 26315069
TI  - Screening of bat faeces for arthropod-borne apicomplexan protozoa: Babesia canis
      and Besnoitia besnoiti-like sequences from Chiroptera.
AB  - BACKGROUND: Bats are among the most eco-epidemiologically important mammals,
      owing to their presence in human settlements and animal keeping facilities.
      Roosting of bats in buildings may bring pathogens of veterinary-medical
      importance into the environment of domestic animals and humans. In this context
      bats have long been studied as carriers of various pathogen groups. However,
      despite their close association with arthropods (both in their food and as their
      ectoparasites), only a few molecular surveys have been published on their role as
      carriers of vector-borne protozoa. The aim of the present study was to compensate
      for this scarcity of information. FINDINGS: Altogether 221 (mostly individual)
      bat faecal samples were collected in Hungary and the Netherlands. The DNA was
      extracted, and analysed with PCR and sequencing for the presence of arthropod
      borne apicomplexan protozoa. Babesia canis canis (with 99-100% homology) was
      identified in five samples, all from Hungary. Because it was excluded with an
      Ixodidae-specific PCR that the relevant bats consumed ticks, these sequences
      derive either from insect carriers of Ba. canis, or from the infection of bats.
      In one bat faecal sample from the Netherlands a sequence having the highest (99%)
      homology to Besnoitia besnoiti was amplified. CONCLUSIONS: These findings suggest
      that some aspects of the epidemiology of canine babesiosis are underestimated or
      unknown, i.e. the potential role of insect-borne mechanical transmission and/or
      the susceptibility of bats to Ba. canis. In addition, bats need to be added to
      future studies in the quest for the final host of Be. besnoiti.

PMID- 26315070
TI  - Peculiarity of Two Thermodynamically-Stable Morphologies and Their Impact on the
      Efficiency of Small Molecule Bulk Heterojunction Solar Cells.
AB  - Structural characteristics of the active layers in organic photovoltaic (OPV)
      devices play a critical role in charge generation, separation and transport. Here
      we report on morphology and structural control of p-DTS(FBTTh2)2:PC71BM films by
      means of thermal annealing and 1,8-diiodooctane (DIO) solvent additive
      processing, and correlate it to the device performance. By combining surface
      imaging with nanoscale depth-sensitive neutron reflectometry (NR) and X-ray
      diffraction, three-dimensional morphologies of the films are reconstituted with
      information extending length scales from nanometers to microns. DIO promotes the
      formation of a well-mixed donor-acceptor vertical phase morphology with a large
      population of small p-DTS(FBTTh2)2 nanocrystals arranged in an elongated domain
      network of the film, thereby enhancing the device performance. In contrast, films
      without DIO exhibit three-sublayer vertical phase morphology with phase
      separation in agglomerated domains. Our findings are supported by thermodynamic
      description based on the Flory-Huggins theory with quantitative evaluation of
      pairwise interaction parameters that explain the morphological changes resulting
      from thermal and solvent treatments. Our study reveals that vertical phase
      morphology of small-molecule based OPVs is significantly different from polymer
      based systems. The significant enhancement of morphology and information obtained
      from theoretical modeling may aid in developing an optimized morphology to
      enhance device performance for OPVs. 

PMID- 26315071
TI  - Prevalence and Treatment of Children's Asthma in Rural Areas Compared with Urban
      Areas in Beijing.
AB  - BACKGROUND: The prevalence of childhood asthma has been increasing in China. This
      study aimed to compare the prevalence, diagnosis, and treatment of asthmatic
      children from urban and rural areas in Beijing, China. METHODS: Schools,
      communities, and kindergartens were randomly selected by cluster random sampling
      from urban and rural areas in Beijing. Parents were surveyed by the same
      screening questionnaires. On-the-spot inquiries, physical examinations, medical
      records, and previous test results were used to diagnose asthmatic children.
      Information on previous diagnoses, treatments, and control of symptoms was
      obtained. RESULTS: From 7209 children in rural areas and 13,513 children in urban
      areas who completed screening questionnaires, 587 children were diagnosed as
      asthma. The prevalence of asthma in rural areas was lower than in urban areas
      (1.25% vs. 3.68%, chi2 = 100.80, P < 0.001). The diagnosis of asthma in rural
      areas was lower than in urban areas (48.9% vs. 73.9%, chi2 = 34.6, P < 0.001).
      Compared with urban asthmatic children (56.5%), only 35.6% of rural asthmatic
      children received inhaled corticosteroids (P < 0.05). The use of bronchodilators
      was also lower in rural areas than in urban areas (56.5% vs. 66.4%, chi2 = 14.2,
      P < 0.01). CONCLUSION: The prevalence of asthma in children was lower in rural
      areas compared with children in the urban area of Beijing. A considerable number
      of children were not diagnosed and inadequately treated in rural areas.

PMID- 26315072
TI  - Obstructive Sleep Apnea Syndrome is Associated with Metabolic Syndrome among
      Adolescents and Youth in Beijing: data from Beijing Child and Adolescent
      Metabolic Syndrome Study.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) syndrome has a negative impact on the
      health of millions of adolescents and youth. The aim of this study was to
      evaluate the associations of OSA syndrome with obesity and cardiometabolic risk
      factors among adolescents and youth at risk for metabolic syndrome (MS). METHODS:
      A total of 558 subjects aged 14-28 years were recruited from the Beijing Child
      and Adolescent Metabolic Syndrome Study. Each underwent a 2-h oral glucose
      tolerance test (OGTT), echocardiography, and liver ultrasonography.
      Anthropometric measures, blood levels of glucose, lipids, and liver enzymes were
      assessed. Subjects with high or low risk for OSA were identified by Berlin
      Questionnaire (BQ). RESULTS: Among the subjects in obesity, 33.7% of whom were
      likely to have OSA by BQ. Subjects with high risk for OSA had higher neck and
      waist circumference and fat mass percentage compared to those with low risk for
      OSA (P < 0.001). Moreover, significant differences in levels of lipids, glucose
      after OGTT, and liver enzymes, as well as echocardiographic parameters were found
      between the two groups with high or low risk for OSA (P < 0.05). The rates of
      nonalcoholic fatty liver disease (71.0% vs. 24.2%), MS (38.9% vs. 7.0%), and its
      components in high-risk group were significantly higher than in low-risk group.
      CONCLUSIONS: The prevalence of OSA by BQ was high in obese adolescents and youth.
      A high risk for OSA indicates a high cardiometabolic risk. Mechanisms mediating
      the observed associations require further investigation.

PMID- 26315073
TI  - A Retrospective Study of 1,526 Cases of Transcatheter Occlusion of Patent Ductus
      Arteriosus.
AB  - BACKGROUND: Patent ductus arteriosus (PDA) is one of the most common congenital
      heart diseases and began to get treated by transcatheter occlusion since 1997 in
      China. Since then, several devices have been invented for occluding PDA. This
      study aimed to evaluate the technical feasibility, safety, and efficacy of
      transcatheter occlusion of PDA with different devices. METHODS: One thousand five
      hundred and twenty-six patients (537 boys, 989 girls) with PDA from January 1997
      to September 2014 underwent descending aortogram and transcatheter occlusion
      procedure. We retrospectively analyzed data of these patients, including gender,
      age, weight, size and morphology of PDA, and devices used in transcatheter
      occlusion, outcomes, and postoperational complications. RESULTS: Median age and
      median weight were 4.0 years (range: 0.3-52.0 years old) and 15.3 kg (range: 4.5
      91.0 kg), respectively. Mean ductal diameter, aortic ductal diameter, ductal
      length, and pulmonary artery pressure were 3.50 +/- 2.15 mm, 10.08 +/- 2.46 mm,
      7.49 +/- 3.02 mm, and 30.21 +/- 17.28 mmHg, respectively. Morphology of PDA
      assessed by descending aortogram was of type A in 1428 patients, type B in 6
      patients, type C in 79 patients, type D in 4 patients, and type E in 9 patients
      according to the classification of Krichenko. Of all the 1526 patients, 1497
      patients underwent transcatheter PDA closure, among which 1492 were successful.
      Devices used were Amplatzer duct occluder I (ADO I, 1280, 85.8%), Cook detachable
      coils (116, 7.8%), ADO II (ADO II, 68, 4.6%), muscular VSD occluder (12, 0.8%),
      and Amplatzer vascular plug (16, 1.0%). CONCLUSIONS: Excellent occlusion rates
      with low complication rates were achieved with all devices regardless of PDA
      types. With transcatheter occlusion technique and devices developing, more
      patients with PDA can be treated with transcatheter closure both safely and
      efficiently.

PMID- 26315074
TI  - Pediatric Heart Transplantation: Report from a Single Center in China.
AB  - BACKGROUND: Although heart transplantation (HTx) has become a standard therapy
      for end-stage heart diseases, experience with pediatric HTx is limited in China.
      In this article, we will try to provide the experience with indications,
      complications, perioperative management, immunosuppressive therapy, and survival
      for pediatric HTx based on our clinical work. METHODS: This is a retrospective
      chart review of the pediatric patients undergoing HTx at Department of
      Cardiovascular Surgery of Union Hospital from September 2008 to December 2014. We
      summarized the indications, surgical variables, postoperative complications, and
      survival for these patients. RESULTS: Nineteen pediatric patients presented for
      HTx at Union Hospital of Tongji Medical College, of whom 10 were male. The age at
      the time of transplantation ranged from 3 months to 18 years (median 15 years).
      Patient weight ranged from 5.2 kg to 57.0 kg (median 38.0 kg). Pretransplant
      diagnosis included cardiomyopathy (14 cases), complex congenital heart disease (3
      cases), and tumor (2 cases). All recipients received ABO-compatible donor hearts.
      Postoperative complications occurred in 12 patients, including cardiac
      dysfunction, arrhythmia, pulmonary infection, renal dysfunction, and rejection.
      Two of them experienced cardiac failure and required extracorporeal membrane
      oxygenation. The immunosuppression regimen was comprised of prednisone, a
      calcineurin inhibitor, and mycophenolate. All patients recovered with New York
      Heart Association (NYHA) Class I-II cardiac function and were discharged. Only
      one patient suffered sudden death 19 months after transplantation. CONCLUSION:
      Orthotopic HTx is a promising therapeutic option with satisfying survival for the
      pediatric population in China with end-stage heart disease.

PMID- 26315075
TI  - Behavioral Symptoms in Motor Neuron Disease and Their Negative Impact on
      Caregiver Burden.
AB  - BACKGROUND: The spectrum of abnormal behaviors in amyotrophic lateral
      sclerosis/motor neuron disease (ALS/MND) has been described, but its practical
      meaning, namely its impact on caregiver burden, has not been clearly documented
      in Chinese population. This study aimed to assess the distribution of abnormal
      behaviors in Chinese population, and to analyze the relationship between behavior
      changes and caregiver burden. METHODS: Sixty-five patients with ALS/MND have been
      consecutively enrolled into registry platform of Peking Union Medical College
      Hospital. An investigation was performed to these patients and their caregivers
      using the revised ALS function rating scale, Frontal Behavioral Inventory-ALS
      version, the Frontal Assessment Battery, and the Caregiver Burden Inventory.
      RESULTS: Twenty-eight (43.1%) patients displayed abnormal behaviors of varying
      degrees, with one fulfilling the diagnostic criteria of frontotemporal lobe
      degeneration. Irritability, logopenia, and inflexibility ranked top 3 of abnormal
      behavior list. Correlation analysis revealed that the degree of behavioral change
      and frontal cognitive status were significantly associated with caregiver burden,
      with more extensive impact from disinhibitive behaviors. Analysis of covariance
      analysis showed that after associated factors were corrected, caregivers of
      patients with moderate to severe behavior change reported significantly heavier
      developmental burden, physical burden, and total burden than those with no
      behavioral change. CONCLUSIONS: Neurobehavioral symptoms could present in around
      40% of Chinese patients with ALS/MND, and the distribution of these behaviors was
      also unique. Besides, abnormal behaviors were highly related to caregivers'
      burden.

PMID- 26315076
TI  - Effect of Continuous Positive Airway Pressure Therapy on Glycemic Excursions and
      Insulin Sensitivity in Patients with Obstructive Sleep Apnea-hypopnea Syndrome
      and Type 2 Diabetes.
AB  - BACKGROUND: For patients with obstructive sleep apnea-hypopnea syndrome (OSAHS)
      and type 2 diabetes mellitus (T2DM), the night sleep interruption and
      intermittent hypoxia due to apnea or hypopnea may induce glycemic excursions and
      reduce insulin sensitivity. This study aimed to investigate the effect of
      continuous positive airway pressure (CPAP) therapy in patients with OSAHS and
      T2DM. METHODS: Continuous glucose monitoring system (CGMS) was used in 40
      patients with T2DM and newly diagnosed OSAHS. The measurements were repeated
      after 30 days of CPAP treatment. Subsequently, insulin sensitivity and
      glycohemoglobin (HbA1c) were measured and compared to the pretreatment data.
      RESULTS: After CPAP therapy, the CGMS indicators showed that the 24-h mean blood
      glucose (MBG) and the night time MBG were significantly reduced (P < 0.05 and P =
      0.03, respectively). The mean ambulatory glucose excursions (MAGEs) and the mean
      of daily differences were also significantly reduced (P < 0.05 and P = 0.002,
      respectively) compared to pretreatment levels. During the night, MAGE also
      significantly decreased (P = 0.049). The differences between the highest and
      lowest levels of blood glucose over 24 h and during the night were significantly
      lower than prior to CPAP treatment (P < 0.05 and P = 0.024, respectively). The 24
      h and night time durations of high blood glucose (>7.8 mmol/L and > 11.1 mmol/L)
      decreased (P < 0.05 and P < 0.05, respectively) after the treatment. In addition,
      HbA1c levels were also lower than those before treatment (P < 0.05), and the
      homeostasis model assessment index of insulin resistance was also significantly
      lower than before CPAP treatment (P = 0.034). CONCLUSIONS: CPAP therapy may have
      a beneficial effect on improving not only blood glucose but also upon insulin
      sensitivity in T2DM patients with OSAHS. This suggests that CPAP may be an
      effective treatment for T2DM in addition to intensive diabetes management.

PMID- 26315077
TI  - Surgical Indications of Exploring Optic Canal and Visual Prognostic Factors in
      Neurosurgical Treatment of Tuberculum Sellae Meningiomas.
AB  - BACKGROUND: Tuberculum sellae meningiomas (TSMs) present a special symptom
      because of the adherence and compression to the optic nerve, optic artery, and
      the chiasm. A significant number of patients with TSMs appear visual deficits.
      This study aimed to investigate the surgical indications of exploring the optic
      canal and visual prognostic factors in the neurosurgical treatment of TSMs.
      METHODS: Totally 21 patients with TSM, who were operated from September 2007 to
      August 2011 in the Department of Neurosurgery, Tongren Hospital were enrolled in
      this study. Results of orbital computed tomography (CT) and magnetic resonance
      imaging (MRI), visual acuity, Goldmann visual field test, orbital color Doppler
      flow imaging (CDI) test in these patients were retrospectively analyzed. RESULTS:
      Visual deficit and optic canal involvement (OCI) were detected in all the 21
      patients. Fourteen patients had bone proliferation within the area of the optic
      canal. After the operation, visual outcomes were improved in 13 patients,
      unchanged in 7 patients, and deteriorated in 1 patient. All the 21 patients
      performed orbital CDI test preoperatively, the results showed that if the peak
      systolic velocity (PSV) of central retinal artery (CRA) value was <= 8 cm/s, the
      visual outcome would be better. CONCLUSIONS: The surgical indications of
      exploring optic canal in TSM cases included: (1) The neuroimaging evidences of
      OCI (CT and/or MRI); (2) PSV of CRA in orbital CDI test was <= 8 cm/s; (3) visual
      acuity was below 0.1; (4) visual field deficit. The PSV of CRA in CDI test could
      be a prognostic factor for visual outcomes of TSMs.

PMID- 26315078
TI  - Biomechanical Comparison of Two Kinds of Internal Fixation in a Type C Zone II
      Pelvic Fracture Model.
AB  - BACKGROUND: Unstable pelvic fractures are complex and serious injuries. Selection
      of a fixation method for these fractures remains a challenging problem for
      orthopedic surgeons. This study aimed to compare the stability of Tile C pelvic
      fractures fixed with two iliosacral (IS) screws and minimally invasive adjustable
      plate (MIAP) combined with one IS screw. METHODS: This study was a biomechanical
      experiment. Six embalmed specimens of the adult pelvis were used. The soft tissue
      was removed from the specimens, and the spines from the fourth lumbar vertebra to
      the proximal one-third of both femurs were retained. The pubic symphysis,
      bilateral sacroiliac joints and ligaments, bilateral hip joints, bilateral
      sacrotuberous ligaments, and bilateral sacrospinous ligaments were intact. Tile C
      pelvic fractures were made on the specimens. The symphysis pubis was fixed with a
      plate, and the fracture on the posterior pelvic ring was fixed with two kinds of
      internal fixation in turn. The specimens were placed in a biomechanical machine
      at a standing neutral posture. A cyclic vertical load of up to 500 N was applied,
      and displacement was recorded. Shifts in the fracture gap were measured by a
      grating displacement sensor. STATISTICAL ANALYSIS USED: Paired-samples t-test.
      RESULTS: Under the vertical load of 100, 200, 300, 400, and 500 N, the average
      displacement of the specimens fixed with MIAP combined with one IS screw was
      0.46, 0.735, 1.377, 1.823, and 2.215 mm, respectively, which was significantly
      lower than that of specimens fixed with two IS screws under corresponding load (P
      < 0.05). Under the vertical load of 500 N, the shift in the fracture gap of
      specimens fixed with MIAP combined with one IS screw was 0.261 +/- 0.095 mm, and
      that of specimens fixed with two IS screws was 0.809 +/- 0.170 mm. The difference
      was significant (P < 0.05). CONCLUSION: The stability of Tile C pelvic fractures
      fixed with MIAP combined with one IS screw was better than that fixed with two IS
      screws.

PMID- 26315079
TI  - Radiological Assessment of the Sacrofemoral Angle: A Novel Method to Measure the
      Range of Hip Joint Flexion.
AB  - BACKGROUND: A quantitative and accurate measurement of the range of hip joint
      flexion (RHF) is necessarily required in the evaluation of disordered or
      artificial hip joint function. This study aimed to assess a novel method to
      measure RHF more accurately and objectively. METHODS: Lateral radiographs were
      taken of 31 supine men with hip joints extended or flexed. Relevant angles were
      measured directly from the radiographs. The change in the sacrofemoral angle
      (SFA) (the angle formed between the axis of the femur and the line tangent to the
      upper endplate of S1) from hip joint extension to hip joint flexion, was proposed
      as the RHF. The validity of this method was assessed via concomitant measurements
      of changes in the femur-horizontal angle (between the axis of the femur and the
      horizontal line) and the sacrum-horizontal angle (SHA) (between the line tangent
      to the upper endplate of S1 and the horizontal line), the difference of which
      should equal the change in the SFA. RESULTS: The mean change in the SFA was 112.5
      +/- 7.4 degrees , and was independent of participant age, height, weight, or body
      mass index. The mean changes in the femur-horizontal and SHAs were 123.0 +/- 6.4
      degrees  and 11.4 +/- 3.0 degrees , respectively. This confirmed that the change
      of SFA between hip joint extension and hip joint flexion was equal to the
      difference between the changes in the femur-horizontal and SHAs. CONCLUSIONS:
      Using the SFA, to evaluate RHF could prevent compromised measurements due to the
      movements of pelvis and lumbar spine during hip flexion, and is, therefore, a
      more accurate and objective method with reasonable reliability and validity.

PMID- 26315080
TI  - Effect of Intravascular Ultrasound-assisted Thoracic Endovascular Aortic Repair
      for "Complicated" Type B Aortic Dissection.
AB  - BACKGROUND: Intravascular ultrasound (IVUS) examination can provide useful
      information during endovascular stent graft repair. However, its actual clinical
      utility in thoracic endovascular aortic repair (TEVAR) for type B aortic
      dissection (type B-AD) remains unclear, especially in complicated aortic
      dissection. We evaluated the effect of IVUS as a complementary tool during TEVAR.
      METHODS: From September 2011 to April 2012, we conducted a prospective cohort
      study of 47 consecutive patients with "complicated" type B-AD diagnosed. We
      divided the patients into two groups: IVUS-assisted TEVAR group and TEVAR using
      angiography alone group. The general procedure of TEVAR was performed. We
      evaluated the perioperative and follow-up events. Patient demographics,
      comorbidities, preoperative images, dissection morphology, details of operative
      strategy, intraoperative events, and postoperative course were recorded. RESULTS:
      A total of 47 patients receiving TEVAR were enrolled. Among them (females, 8.51%;
      mean age, 57.38 +/- 13.02 years), 13 cases (27.66%) were selected in the IVUS
      assisted TEVAR group, and 34 were selected in the TEVAR group. All patients were
      symptomatic. The average diameter values of IVUS measurements in the landing zone
      were greater than those estimated by computed tomography angiography (31.82 +/-
      4.21 mm vs. 30.64 +/- 4.13 mm, P < 0.001). The technique success rate was 100%.
      Among the postoperative outcomes, statistical differences were only observed
      between the IVUS-assisted TEVAR group and TEVAR group for total operative time
      and the amount of contrast used (P = 0.013 and P < 0.001, respectively). The
      follow-up ranged from 15 to 36 months for the IVUS-assisted TEVAR group and from
      10 to 35 months for the TEVAR group (P = 0.646). The primary endpoints were no
      statistical difference in the two groups. CONCLUSIONS: Intraoperative IVUS
      assisted TEVAR is clinically feasible and safe. For the endovascular repair of
      "complicated" type B-AD, IVUS may be helpful for understanding dissection
      morphology and decrease the operative time and the amount of contrast used.

PMID- 26315081
TI  - Activation of gamma-aminobutyric Acid (A) Receptor Protects Hippocampus from
      Intense Exercise-induced Synapses Damage and Apoptosis in Rats.
AB  - BACKGROUND: Our previous study has confirmed that one bout of exhaustion (Ex) can
      cause hippocampus neurocyte damage, excessive apoptosis, and dysfunction. Its
      initial reason is intracellular calcium overload in hippocampus triggered by N
      methyl-D-aspartic acid receptor (NMDAR) over-activation. NMDAR activation can be
      suppressed by gamma-aminobutyric acid (A) receptor (GABAAR). Whether GABAAR can
      prevent intense exercise-induced hippocampus apoptosis, damage, or dysfunction
      will be studied in this study. METHODS: According to dose test, rats were
      randomly divided into control (Con), Ex, muscimol (MUS, 0.1 mg/kg) and
      bicuculline (BIC, 0.5 mg/kg) groups, then all rats underwent once swimming Ex
      except ones in Con group only underwent training. Intracellular free calcium
      concentration ([Ca2+]i) was measured by Fura-2-acetoxymethyl ester; glial
      librillary acidic protein (GFAP) and synaptophysin (SYP) immunofluorescence were
      also performed; apoptosis were displayed by dUTP nick end labeling (TUNEL) stain;
      endoplasmic reticulum stress-induced apoptosis pathway was detected by Western
      blotting analysis; Morris water maze was used to detect learning ability and
      spatial memory. RESULTS: The appropriate dose was 0.1 mg/kg for MUS and 0.5 mg/kg
      for BIC. Ex group showed significantly increased [Ca2+]i and astrogliosis; TUNEL
      positive cells and levels of GFAP, B cell lymphoma-2 (Bcl-2) associated X protein
      (Bax), caspase-3, caspase-12 cleavage, CCAAT/enhancer binding protein homologous
      protein (CHOP), and p-Jun amino-terminal kinase (p-JNK) in Ex group also raised
      significantly compared to Con group, while SYP, synapse plasticity, and Bcl-2
      levels in Ex group were significantly lower than those in Con group. These
      indexes were back to normal in MUS group. BIC group had the highest levels of
      [Ca2+]i, astrogliosis, TUNEL positive cell, GFAP, Bax, caspase-3, caspase-12
      cleavage, CHOP, and p-JNK, it also gained the lowest SYP, synapse plasticity, and
      Bcl-2 levels among all groups. Water maze test showed that Ex group had longer
      escape latency (EL) and less quadrant dwell time than Con group; all indexes
      between MUS and Con groups had no significant differences; BIC had the longest EL
      and least quadrant dwell time among all groups. CONCLUSIONS: Activation of GABAA
      R could prevent intense exercise-induced synapses damage, excessive apoptosis,
      and dysfunction of hippocampus.

PMID- 26315082
TI  - Antinociceptive Effect of Najanalgesin from Naja Naja Atra in a Neuropathic Pain
      Model via Inhibition of c-Jun NH2-terminal Kinase.
AB  - BACKGROUND: Najanalgesin, a toxin isolated from the venom of Naja naja atra, has
      been shown to exert significant analgesic effects in a neuropathic pain model in
      rats. However, the molecular mechanism underlying this protective effect of
      najanalgesin is poorly understood. The present study sought to evaluate the
      intracellular signaling pathways that are involved in the antinociceptive effect
      of najanalgesin on neuropathic pain. METHODS: The antinociceptive properties of
      najanalgesin were tested in hind paw withdrawal thresholds in response to
      mechanical stimulation. We analyzed the participation of the mitogen-activated
      protein kinase p38, extracellular-regulated kinase (ERK), and c-Jun N-terminal
      kinase (JNK) by western blot analysis. This inhibition of JNK was confirmed by
      immunohistochemistry. RESULTS: The phosphorylation levels of JNK (as well as its
      downstream molecule c-Jun), p38, and ERK were significantly increased after
      injury. Najanalgesin only inhibited JNK and c-Jun phosphorylation but had no
      effect on either ERK or p38. This inhibition of JNK was confirmed by
      immunohistochemistry, which suggested that the antinociceptive effect of
      najanalgesin on spinal nerve ligation-induced neuropathic pain in rats is
      associated with JNK activation in the spinal cord. CONCLUSION: The
      antinociceptive effect of najanalgesin functions by inhibiting the JNK in a
      neuropathic pain model.

PMID- 26315083
TI  - Wnt/Glycogen Synthase Kinase 3beta/beta-catenin Signaling Activation Mediated
      Sevoflurane Preconditioning-induced Cardioprotection.
AB  - BACKGROUND: Sevoflurane preconditioning (SP) has been shown to invoke potent
      myocardial protection in animal studies and clinical trials. However, the
      mechanisms underlying SP are complex and not yet well understood. We investigated
      the hypothesis that the cardioprotection afforded by SP is mediated via the
      Wnt/glycogen synthase kinase 3beta (GSK3beta)/beta-catenin signaling pathway.
      METHODS: Two models were established: a Langendorff perfused rat heart model and
      the H9C2 cell hypoxia/reoxygenation model. Both rats and H9C2 cells were randomly
      divided into 6 groups as follows: S group, ischemia-reperfusion (I/R) group, DMSO
      group, IWP group, SP group, and SP + IWP group. Hemodynamic parameters, lactate
      dehydrogenase (LDH) activity in coronary effluent and cell culture supernatant,
      and the infarct size were measured to evaluate myocardial ischemia-reperfusion
      injuries. To determine the activity of Wnt/GSK3beta/beta-catenin signaling
      pathway, the expressions of Wnt3a, phospho-GSK3beta, and beta-catenin were
      measured by Western blotting. RESULTS: SP improved cardiac function recovery,
      reduced infarct size (18 +/- 2% in the SP group compared with 35 +/- 4% in the
      I/R group; P < 0.05), decreased LDH activity in coronary effluent, and culture
      supernatant. IWP-2, an inhibitor of Wnt, abolished the cardioprotection by SP. In
      addition, Western blotting analysis demonstrated that the expressions of Wnt3a,
      phospho-GSK3beta, and beta-catenin significantly (P < 0.05) increased in the I/R
      group, compared with the S group; and compared to I/R group, SP significantly (P
      < 0.05) increased Wnt3a, phospho-GSK3beta, and beta-catenin expressions.
      Pretreatment with IWP-2 significantly (P < 0.05) abolished SP-induced
      Wnt/GSK3beta/beta-catenin signaling activation. CONCLUSIONS: The results showed
      for thefirst time that cardioprotection afforded by SP may be mediated partly via
      the Wnt/GSK3beta/beta-catenin signaling pathway.

PMID- 26315084
TI  - Do Different Cyclooxygenase Inhibitors Impair Rotator Cuff Healing in a Rabbit
      Model?
AB  - BACKGROUND: The effect of selective and non-selective cyclooxygenase (COX)
      inhibitors on tendon healing was variable. The purpose of the study was to
      evaluate the influence of non-selective COX inhibitor, ibuprofen and flurbiprofen
      axetil and selective COX-2 inhibitor, celecoxib on the tendon healing process in
      a rabbit model. METHODS: Ninety-six New Zealand rabbits were used as rotator cuff
      repair models. After surgery, they were divided randomly into four groups:
      ibuprofen (10 mg.kg-1.d-1), celecoxib (8 mg.kg-1.d-1), flurbiprofen axetil (2
      mg.kg-1.d-1), and control group (blank group). All drugs were provided for 7
      days. Rabbits in each group were sacrificed at 3, 6, and 12 weeks after tendon
      repair. Tendon biomechanical load failure tests were performed. The percentage of
      type I collagen on the bone tendon insertion was calculated by Picric acid Sirius
      red staining and image analysis. All data were compared among the four groups at
      the same time point. All data in each group were also compared across the
      different time points. Qualitative histological evaluation of the bone tendon
      insertion was also performed among groups. RESULTS: The load to failure increased
      significantly with time in each group. There were significantly lower failure
      loads in the celecoxib group than in the control group at 3 weeks (0.533 vs.
      0.700, P = 0.002), 6 weeks (0.607 vs. 0.763, P = 0.01), and 12 weeks (0.660 vs.
      0.803, P = 0.002), and significantly lower percentage of type I collagen at 3
      weeks (11.5% vs. 27.6%, P = 0.001), 6 weeks (40.5% vs. 66.3%, P = 0.005), and 12
      weeks (59.5% vs. 86.3%, P = 0.001). Flurbiprofen axetil showed significant
      differences at 3 weeks (failure load: 0.600 vs. 0.700, P = 0.024; percentage of
      type I collagen: 15.6% vs. 27.6%, P = 0.001), but no significant differences at 6
      and 12 weeks comparing with control group, whereas the ibuprofen groups did not
      show any significant difference at each time point. CONCLUSIONS: Nonsteroidal
      anti-inflammatory drugs can delay tendon healing in the early stage after rotator
      cuff repair. Compared with nonselective COX inhibitors, selective COX-2
      inhibitors significantly impact tendon healing.

PMID- 26315085
TI  - Protective Effects of Estradiol on Myocardial Contractile Function Following
      Hemorrhagic Shock and Resuscitation in Rats.
AB  - BACKGROUND: Hemorrhagic shock (HS) results in myocardial contractile dysfunction.
      Studies showed that 17beta-estradiol protects the myocardium against contractile
      dysfunction. The study investigated the cardioprotective effects of treatment
      with 17beta-estradiol before resuscitation following 1 h of HS and resuscitation.
      METHODS: Male Sprague-Dawley rats were assigned to 2 sets of experimental
      protocols: Ex vivo and in vivo treatment and resuscitation. Each set had three
      experimental groups (n = 6 per group): Normotensive (N), HS and resuscitation (HS
      R) and HS rats treated with 17beta-estradiol (E) and resuscitated (HS-E-R). Rats
      were hemorrhaged over 60-min to reach a mean arterial blood pressure of 40 mmHg.
      In the ex vivo group, hearts were resuscitated by perfusion in the Langendorff
      system. In the 17beta-estradiol treated group, 17beta-estradiol 280 ug/kg was
      added for thefirst 5 min. Cardiac function was measured. Left ventricular
      generated pressure (LVGP) and +dP/dt were calculated. In the in vivo group, rats
      were treated with 17beta-estradiol 280 ug/kg s.c. after 60-min HS. Resuscitation
      was performed in vivo by the reinfusion of the shed blood for 30-min to restore
      normotension. RESULTS: Treatment with 17beta-estradiol before resuscitation in ex
      vivo treated and resuscitated isolated hearts and in the in vivo treated and
      resuscitated rats following HS improved myocardial contractile function. In the
      in vivo treated group, LVGP and +dP/dt max were significantly higher in 17beta
      estradiol treated rats compared to the untreated group (LVGP 136.40 +/- 6.61
      compared to 47.58 +/- 17.55, and +dP/dt 661.85 +/- 49.88 compared to 88.18 +/-
      0.85). Treatment with 17beta-estradiol improved LVGP following HS. CONCLUSIONS:
      The results indicate that treatment with 17beta-estradiol before resuscitation
      following HS protects the myocardium against dysfunction.

PMID- 26315086
TI  - Effects of Continuous Positive Airway Pressure on Cognitive Deficits in Middle
      aged Patients with Obstructive Sleep Apnea Syndrome: A Meta-analysis of
      Randomized Controlled Trials.
AB  - BACKGROUND: Current views on continuous positive airway pressure (CPAP) treatment
      to improve the cognitive deficits of patients with obstructive sleep apnea
      syndrome (OSAS) are controversial, so we performed a meta-analysis. METHODS: A
      comprehensive literature search was undertaken in PubMed, CINAHL, Medline,
      PsycInfo, EMBASE, Cochrane Library, CNKI, WanFang, VIP, and CBMdisc for studies
      published from June 1971 to July 2014. The outcome measures included
      neuropsychological tests of the 7 cognitive domains detailed below. RESULTS:
      After screening the titles and abstracts and thoroughly reading the full text, we
      obtained 13 studies with little risk of bias that incorporated 1744 middle-aged
      obese participants with mild to severe OSAS. The studies were published from 1994
      to 2012. Treatment durations varied from 1 to 24 weeks. The effect sizes of
      attention, vigilance, processing speed, working memory, memory, verbal fluency,
      and visuoconstructive skills domains were -0.10 (P = 0.24), -0.12 (P = 0.04), 
      0.08 (P = 0.16), 0.00 (P = 0.95), -0.04 (P = 0.30), -0.06 (P = 0.34), and -0.01
      (P = 0.92), respectively. CONCLUSIONS: Cognition partially improved in patients
      with OSAS after CPAP treatment. The only domain with significant improvement was
      vigilance. Rigorous randomized controlled trials need to be performed to obtain
      clear results.

PMID- 26315087
TI  - Sources of Heterogeneity in Trials Reporting Hydroxyethyl Starch 130/0.4 or 0.42
      Associated Excess Mortality in Septic Patients: A Systematic Review and Meta
      regression.
AB  - BACKGROUND: This meta-analysis was to determine the association of the cumulative
      dose of 130/0.4 or 0.42 (hydroxyethyl starch [HES] 130/0.4*) or delta daily fluid
      balance (i.e., daily fluid balance in HES group over or below control group) with
      the heterogeneity of risk ratio (RR) for mortality in randomized control trials
      (RCTs). METHODS: Three databases (PubMed, EMBASE, Cochrane) were searched to
      identify prospective RCTs reporting mortality in adult patients with sepsis to
      compare HES130/0.4* with crystalloids or albumin. Meta-analysis was performed
      using random effects. Sensitivity and meta-regression analyses were used to
      examine the heterogeneity sources of RR for mortality. RESULTS: A total number of
      4408 patients from 11 RCTs were included. The pooled RR showed no significant
      difference for overall mortality in patients with administration of HES130/0.4*
      compared with treatment of control fluids (RR: 1.02, 95% confidence interval:
      0.90-1.17; P = 0.73). Heterogeneity was moderate across recruited trials (I2 =
      34%, P = 0.13). But, a significant variation was demonstrated in subgroup with
      crystalloids as control fluids (I2 = 42%, P < 0.1). Sensitivity analysis revealed
      that trials with high risk of bias did not significantly impact the pooled
      estimates for mortality. Meta-regression analysis also did not determine a dose
      effect relationship of HES130/0.4* with mortality (P = 0.298), but suggested
      daily delta fluid balance being likely associated with mortality in septic
      patients receiving HES130/130/0.4* (P = 0.079). CONCLUSIONS: Inappropriate daily
      positive fluid balance was likely an important source of heterogeneity in these
      trials reporting HES130/0.4* associated with excess mortality in septic patients.

PMID- 26315088
TI  - Perioperative Red Blood Cell Transfusion: What We Do Not Know.
AB  - OBJECTIVE: Blood transfusion saves lives but may also increase the risk of
      injury. The objective of this review was to evaluate the possible adverse effects
      related to transfusion of red blood cell (RBC) concentrates stored for prolonged
      periods. DATA SOURCES: The data used in this review were mainly from PubMed
      articles published in English up to February 2015. STUDY SELECTION: Clinical and
      basic research articles were selected according to their relevance to this topic.
      RESULTS: The ex vivo changes to RBC that occur during storage are collectively
      called storage lesion. It is still inconclusive if transfusion of RBC with
      storage lesion has clinical relevance. Multiple ongoing prospective randomized
      controlled trials are aimed to clarify this clinical issue. It was observed that
      the adverse events related to stored RBC transfusion were prominent in certain
      patient populations, including trauma, critical care, pediatric, and cardiac
      surgery patients, which leads to the investigation of underlying mechanisms. It
      is demonstrated that free hemoglobin toxicity, decreasing of nitric oxide
      bioavailability, and free iron-induced increasing of inflammation may play an
      important role in this process. CONCLUSION: It is still unclear whether
      transfusion of older RBC has adverse effects, and if so, which factors determine
      such clinical effects. However, considering the magnitude of transfusion and the
      widespread medical significance, potential preventive strategies should be
      considered, especially for the susceptible recipients.

PMID- 26315089
TI  - Current and Future Clinical Applications of Zinc Transporter-8 in Type 1 Diabetes
      Mellitus.
AB  - OBJECTIVE: To evaluate the utility of zinc transporter-8 (ZnT8) in the
      improvement of type 1 diabetes mellitus (T1DM) diagnosis and prediction, and to
      explore whether ZnT8 is a potential therapeutic target in T1DM. DATA SOURCES: A
      search was conducted within the medical database PubMed for relevant articles
      published from 2001 to 2015. The search terms are as follows: "ZnT8," "type 1
      diabetes," "latent autoimmune diabetes in adults," "type 2 diabetes," "islet
      autoantibodies," "zinc supplement," "T cells," "beta cell," "immune therapy." We
      also searched the reference lists of selected articles. STUDY SELECTION: English
      language original articles and critical reviews concerning ZnT8 and the clinical
      applications of islet autoantibodies in diabetes were reviewed. RESULTS: The
      basic function of ZnT8 is maintaining intracellular zinc homeostasis, which
      modulates the process of insulin biosynthesis, storage, and secretion.
      Autoantibodies against ZnT8 (ZnT8A) and ZnT8-specific T cells are the reliable
      biomarkers for the identification, stratification, and characterization of T1DM.
      Additionally, the results from the animal models and clinical trials have shown
      that ZnT8 is a diabetogenic antigen, suggesting the possibility of ZnT8-specific
      immunotherapy as an alternative for T1DM therapy. CONCLUSIONS: ZnT8 is a novel
      islet autoantigen with a widely potential for clinical applications in T1DM.
      However, before the large-scale clinical applications, there are still many
      problems to be solved.

PMID- 26315091
TI  - Multiple Arthroplasty in a Patient with Alkaptonuric Arthritis.

PMID- 26315090
TI  - Genomics-based Approach and Prognostic Stratification Significance of Gene
      Mutations in Intermediate-risk Acute Myeloid Leukemia.
AB  - OBJECTIVE: Intermediate-risk acute myeloid leukemia (IR-AML), which accounts for
      a substantial number of AML cases, is highly heterogeneous. We systematically
      summarize the latest research progress on the significance of gene mutations for
      prognostic stratification of IR-AML. DATA SOURCES: We conducted a systemic search
      from the PubMed database up to October, 2014 using various search terms and their
      combinations including IR-AML, gene mutations, mutational analysis, prognosis,
      risk stratification, next generation sequencing (NGS). STUDY SELECTION: Clinical
      or basic research articles on NGS and the prognosis of gene mutations in IR-AML
      were included. RESULTS: The advent of the era of whole-genome sequencing has led
      to the discovery of an increasing number of molecular genetics aberrations that
      involved in leukemogenesis, and some of them have been used for prognostic risk
      stratification. Several studies have consistently identified that some gene
      mutations have prognostic relevance, however, there are still many controversies
      for some genes because of lacking sufficient evidence. In addition, tumor cells
      harbor hundreds of mutated genes and multiple mutations often coexist, therefore,
      single mutational analysis is not sufficient to make accurate prognostic
      predictions. The comprehensive analysis of multiple mutations based on
      sophisticated genomic technologies has raised increasing interest in recent
      years. CONCLUSIONS: NGS represents a pioneering and helpful approach to
      prognostic risk stratification of IR-AML patients. Further large-scale studies
      for comprehensive molecular analysis are needed to provide guidance and a
      theoretical basis for IR-AML prognostic stratification and clinical management.

PMID- 26315092
TI  - Clinical Analysis of Breast Lactation after Laparoscopic Cholecystectomy in
      Nonlactation Period.

PMID- 26315093
TI  - Insulin Autoimmune Syndrome: 73 Cases of Clinical Analysis.

PMID- 26315094
TI  - Claiming "New" in What Might be an Inadequate Search.

PMID- 26315095
TI  - Clinical Features of an Unrecognized 21-hydroxylase Deficiency Woman During
      Controlled Ovarian Hyperstimulation.

PMID- 26315096
TI  - Acute Inferior Myocardial Infarction as the First Manifestation of Takayasu
      Arteritis in a Young Boy.

PMID- 26315098
TI  - Design and simulation of an optimized e-linac based neutron source for BNCT
      research.
AB  - The paper is focused on the study of a novel photo-neutron source for BNCT
      preclinical research based on medical electron Linacs. Previous studies by the
      authors already demonstrated the possibility to obtain a mixed thermal and
      epithermal neutron flux of the order of 10(7) cm(-2) s(-1). This paper
      investigates possible Linac's modifications and a new photo-converter design to
      rise the neutron flux above 5 10(7) cm(-2) s(-1), also reducing the gamma
      contamination.

PMID- 26315099
TI  - Comparison of EPR response of alanine and Gd2O3-alanine dosimeters exposed to
      TRIGA Mainz reactor.
AB  - In this work we report some preliminary results regarding the analysis of
      electron paramagnetic resonance (EPR) response of alanine pellets and alanine
      pellets added with gadolinium used for dosimetry at the TRIGA research reactor in
      Mainz, Germany. Two set-ups were evaluated: irradiation inside PMMA phantom and
      irradiation inside boric acid phantom. We observed that the presence of Gd2O3
      inside alanine pellets increases the EPR signal by a factor of 3.45 and 1.24 in
      case of PMMA and boric acid phantoms, respectively. We can conclude that in the
      case of neutron beam with a predominant thermal neutron component the addition of
      gadolinium oxide can significantly improve neutron sensitivity of alanine
      pellets. Monte Carlo (MC) simulations of both response of alanine and Gd-added
      alanine pellets with FLUKA code were performed and a good agreement was achieved
      for pure alanine dosimeters. For Gd2O3-alanine deviations between MC simulations
      and experimental data were observed and discussed. 

PMID- 26315097
TI  - Snake venoms are integrated systems, but abundant venom proteins evolve more
      rapidly.
AB  - BACKGROUND: While many studies have shown that extracellular proteins evolve
      rapidly, how selection acts on them remains poorly understood. We used snake
      venoms to understand the interaction between ecology, expression level, and
      evolutionary rate in secreted protein systems. Venomous snakes employ well
      integrated systems of proteins and organic constituents to immobilize prey.
      Venoms are generally optimized to subdue preferred prey more effectively than non
      prey, and many venom protein families manifest positive selection and rapid gene
      family diversification. Although previous studies have illuminated how individual
      venom protein families evolve, how selection acts on venoms as integrated
      systems, is unknown. RESULTS: Using next-generation transcriptome sequencing and
      mass spectrometry, we examined microevolution in two pitvipers, allopatrically
      separated for at least 1.6 million years, and their hybrids. Transcriptomes of
      parental species had generally similar compositions in regard to protein
      families, but for a given protein family, the homologs present and concentrations
      thereof sometimes differed dramatically. For instance, a phospholipase A2
      transcript comprising 73.4 % of the Protobothrops elegans transcriptome, was
      barely present in the P. flavoviridis transcriptome (<0.05 %). Hybrids produced
      most proteins found in both parental venoms. Protein evolutionary rates were
      positively correlated with transcriptomic and proteomic abundances, and the most
      abundant proteins showed positive selection. This pattern holds with the addition
      of four other published crotaline transcriptomes, from two more genera, and also
      for the recently published king cobra genome, suggesting that rapid evolution of
      abundant proteins may be generally true for snake venoms. Looking more broadly at
      Protobothrops, we show that rapid evolution of the most abundant components is
      due to positive selection, suggesting an interplay between abundance and
      adaptation. CONCLUSIONS: Given log-scale differences in toxin abundance, which
      are likely correlated with biosynthetic costs, we hypothesize that as a result of
      natural selection, snakes optimize return on energetic investment by producing
      more of venom proteins that increase their fitness. Natural selection then acts
      on the additive genetic variance of these components, in proportion to their
      contributions to overall fitness. Adaptive evolution of venoms may occur most
      rapidly through changes in expression levels that alter fitness contributions,
      and thus the strength of selection acting on specific secretome components.

PMID- 26315100
TI  - [Undesirable pigmentation].
AB  - BACKGROUND: Homogenous pigmentation can be induced by alpha-melanocyte
      stimulating hormone (MSH) homologues. Cosmetically inacceptable pigmentation is
      mostly located on the face. OBJECTIVES: Although afamelatonide is a prescription
      drug for the orphan disease erthropoetic protoporphyria, structurally related
      alpha-MSH derivatives are available via the internet. Preventive and
      therapeutical options are necessary for postinflammatory hyperpigmentation,
      melasma, and lentigines. METHODS: Case reports address activation of dysplastic
      naevi by melanotan I. Wood's lamp is of some use in analyzing the level of
      hyperpigmentation. However, no guidelines have been established; thus, a summary
      of current studies is presented. RESULTS: Melanotan I leads to the activation of
      dysplastic nevi. The gold standard for hyperpigmentation is triple therapy with
      hydrochinon, tretinoin, and steroids, which can cause irritation and lead to
      ochronosis in some individuals. Tyrosinase inhibitors, substances that increase
      the cell turnover, and plant derivatives are less efficient but more tolerable.
      CONCLUSIONS: Melanotan I and bleaching creams, which may possibly contain
      mercury, are dangerous. Hyperpigmentation is best treated using a combination
      therapy that inhibits melanocyte activity and melanin synthesis, removes melanin,
      destroys melanin granules, and includes UV protection. Especially in Fitzpatrick
      skin types IV-VI, cryotherapy and laser are not the first line treatment options
      due to renewed posttreatment hyperpigmentation.

PMID- 26315101
TI  - [Complex decongestive therapy].
AB  - The amount of physical pressure plays an important role in complex decongestive
      therapy (CDT). As a function of pressure, microcirculation takes place between
      blood vessels and tissue. As part of the total lymphatic system, lymphatic
      vessels transport the lymphatic load from the interstitial space to the blood
      stream. The lymphatic vessel system, characterized by specific anatomical
      conditions like initial lymphatic vessels, precollectors, collectors, and
      lymphatic strains, is the therapeutic target of complex decongestive therapy.
      Components of CDT include manual lymphatic drainage, compression therapy,
      decongestive kinesitherapy, and good skin care, which increase the transport
      capacity of the lymphatic vessel system. Currently, CDT is acknowledged as the
      main conservative treatment of lymphedema of primary and secondary genesis,
      lipolymphedema, and phlebolymphedema. In clinical practice, we are increasingly
      confronted with edema of multifactorial genesis requiring a critical discussion
      and stocktaking of comprehensive clinical findings in terms of the indication for
      CDT. Therapeutic success depends on a joint application of all CDT components and
      patient compliance. To an increasing extent, medical research tries to combine
      successfully CDT with adjunct treatment options.

PMID- 26315102
TI  - Dyslipidemia in chronic kidney disease.

PMID- 26315103
TI  - Neural reward processing in individuals remitted from major depression.
AB  - BACKGROUND: Dysfunctional behavioural and neural processing of reward has been
      found in currently depressed individuals. However, little is known about altered
      reward processing in remitted depressed individuals. METHOD: A total of 23
      medication-free individuals with remitted major depressive disorder (rMDD) and 23
      matched healthy controls (HCs) performed a reward task during functional magnetic
      resonance imaging. We also investigated reward dependence, novelty seeking and
      harm avoidance using the Tridimensional Personality Questionnaire and their
      association with neural responses of reward processing. RESULTS: Compared to HCs,
      individuals with rMDD exhibited enhanced responses to reward-predicting cues in
      the hippocampus, amygdala and superior frontal gyrus. When reward was delivered,
      rMDD subjects did not significantly differ from HCs. In both groups neural
      activity during reward anticipation was negatively correlated with harm
      avoidance. CONCLUSIONS: Our results show that rMDD is characterized by
      hyperactivation in fronto-limbic regions during reward anticipation. Alterations
      in neural activation during reward processing might reflect an increased effort
      in remitted depressed individuals to allocate neural activity for executive and
      evaluative processes during anticipatory reward processing.

PMID- 26315104
TI  - Informal caregivers of clients with neurological conditions: profiles, patterns
      and risk factors for distress from a home care prevalence study.
AB  - BACKGROUND: Individuals living in the community with neurological conditions
      receive the majority of their care from informal caregivers. The purpose of this
      project was to provide a profile of caregivers of home care clients with
      neurological conditions. The study also examined prevalence of caregiver distress
      and the association between neurological conditions and other client and
      caregiver characteristics with distress. METHODS: The study population included
      Canadian home care clients in the Winnipeg Regional Health Authority in Manitoba
      and in the province of Ontario. Clients with RAI-Home Care (RAI-HC) assessment
      data from 2003 to 2010 were examined. Neurological conditions of interest
      included Alzheimer's disease and related dementias, multiple sclerosis,
      amyotrophic lateral sclerosis, Parkinson's disease, Huntington disease, epilepsy,
      muscular dystrophy, cerebral palsy, traumatic brain injury, spinal cord injury,
      and stroke. Descriptive statistics were analyzed to describe home care client
      characteristics and caregiver characteristics for each neurological condition.
      Logistic regression analysis was used to identify risk factors associated with
      caregiver distress. RESULTS: A substantial proportion of home care clients were
      found to have one or more of the neurological conditions (38.8% to 41.9%).
      Caregiver distress was twice as prevalent among caregivers of clients with
      neurological conditions (28.0%). The largest associations with caregiver distress
      were the amount of informal care hours provided in a week and the MAPLe
      algorithm, an indicator of a client's level of priority for care. After
      adjustment for client characteristics, Huntington disease was the neurological
      condition most strongly associated with caregiver distress. However, clients'
      clinical characteristics and informal care hours had a stronger association with
      caregiver distress than the presence of a neurological condition. Provision of
      formal home care services provided a protective effect from caregiver distress.
      CONCLUSIONS: Neurological conditions are common among home care clients and a
      significant proportion of informal caregivers providing care to these clients
      experience distress. The complexity of clients with neurological conditions
      suggests the need for multicomponent support strategies for informal caregivers.

PMID- 26315105
TI  - Cytokine serum levels during post-transplant adverse events in 61 pediatric
      patients after hematopoietic stem cell transplantation.
AB  - BACKGROUND: Veno-occlusive disease, Graft-versus-Host disease, invasive or
      localized bacterial, viral and fungal infections are known as adverse events
      after hematopoietic stem cell transplantation representing the major cause for
      morbidity and mortality. Detection and differentiation of these adverse events
      are based on clinical symptoms and routine measurements of laboratory parameters.
      METHODS: To identify the role of cytokines as a possible complication-marker for
      adverse events, 61 consecutive pediatric patients with a median age of 7.0 years
      who underwent hematopoietic stem cell transplantation were enrolled in this
      single-center retrospective study. Interleukin-1 beta (IL-1beta), soluble
      interleukin-2 receptor (sIL-2R), interleukin-6 (IL-6), interleukin-8 (IL-8),
      interleukin-10 (IL-10) and tumor necrosis factor-alpha serum (TNF-alpha) levels
      were regularly assessed after transplantation and during transplantation related
      adverse events. RESULTS: Veno-occlusive disease was accompanied by a significant
      increase in levels of IL-6, IL-8 and TNF-alpha.Graft-versus-Host disease was
      associated with a significant increase of IL-10, sIL-2R, IL-6 and TNF-alpha,
      depending on the respective stage or grade. Cytokine IL-6 enabled a significant
      differentiation between sepsis and fungemia, sepsis and viremia, and sepsis and
      bacteremia. Moreover, cytokine IL-8 enabled a significant differentiation between
      sepsis and viremia, sepsis and bacteremia, and bacteremia and viremia whereas IL
      10 made a distinction between sepsis and viremia possible. CONCLUSION: The data
      demonstrate that proinflammatory cytokines might be putative indicators for early
      detection and differentiation of post-transplant adverse events and may allow
      prompt and adequate clinical intervention. Prospective clinical trials are needed
      to evaluate these findings.

PMID- 26315107
TI  - Use of vemurafenib in a patient unable to swallow whole.
AB  - The treatment landscape for metastatic melanoma has increased dramatically in the
      past five years, with the pivotal discovery of activating BRAF mutations in half
      of all melanomas spurring the development for effective treatments that target
      mitogen-activated protein kinase (RAS/RAF/MEK/ERK) pathway. Vemurafenib, a
      selective mutant BRAF Val600 inhibitor, results in striking tumour responses and
      a survival advantage over conventional chemotherapy. We present here the case of
      a 38-year-old woman with metastatic BRAFV600E mutant melanoma and a severe tablet
      phobia, who was found to have been crushing and/or chewing her vemurafenib
      tablets. In this case, she attained a partial response and significant clinical
      benefit, albeit temporarily. 

PMID- 26315106
TI  - Specific expression and export of the Plasmodium falciparum Gametocyte EXported
      Protein-5 marks the gametocyte ring stage.
AB  - BACKGROUND: Plasmodium falciparum sexual development plays a fundamental role in
      the transmission and spread of malaria. The ability to generate gametocytes can
      be lost during culture in vitro, often associated with the loss of a subtelomeric
      region of chromosome 9. Gametocytogenesis starts with erythrocyte invasion by a
      sexually committed merozoite, but the first available specific marker of sexual
      differentiation appears only from 24 h post invasion. METHODS: Specific
      antibodies and gene fusions were produced to study the timing of expression and
      the sub-cellular localization of the P. falciparum Gametocyte EXported Protein-5
      (PfGEXP5), encoded in the subtelomeric region of chromosome 9. Expression
      patterns were examined in wild-type parasites and in parasite lines mutated in
      the Apetala2-G (AP2-G) transcription factor, governing a cascade of early sexual
      stage specific genes. RESULTS: PfGEXP5 is highly expressed in early sexual stages
      and it is actively exported to the infected erythrocyte cytoplasm from as early
      as 14 h post-invasion in haemozoin-free, ring stage-like parasites. The pattern
      of PfGEXP5 expression and export is similar in wild-type parasites and in
      independent AP2-G defective parasite lines unable to produce gametocytes.
      CONCLUSIONS: PfGEXP5 represents the earliest post-invasion sexual stage marker
      described to date. This provides a tool that can be used to identify sexually
      committed ring stage parasites in natural infections. This early gametocyte
      marker would enable the identification and mapping of malaria transmission
      reservoirs in human populations and the study of gametocyte sequestration
      dynamics in infected individuals. The fact that regulation of PfGEXP5 does not
      depend on the AP2-G master regulator of parasite sexual development suggests
      that, after sexual commitment, differentiation progresses through multiple
      checkpoints in the early phase of gametocytogenesis.

PMID- 26315108
TI  - Prognostic Role of a Multimarker Analysis of Circulating Tumor Cells in Advanced
      Gastric and Gastroesophageal Adenocarcinomas.
AB  - OBJECTIVE: We aimed to assess the prognostic value of circulating tumor cells
      (CTC) in patients with advanced gastric and gastroesophageal adenocarcinomas.
      METHODS: The presence of CTC was evaluated in 62 patients with advanced gastric
      and gastroesophageal adenocarcinomas before systemic therapy and at follow-up
      through immunomagnetic enrichment for mucin 1- and epithelial cell adhesion
      molecule (EpCAM)-positive cells, followed by real-time RT-PCR of the tumor
      associated genes KRT19, MUC1, EPCAM, CEACAM5 and BIRC5. RESULTS: The patients
      were stratified into groups according to CTC detection (CTC negative: with all
      marker genes negative; CTC positive: with at least 1 of the marker genes
      positive). Patients who were CTC positive at baseline had a significantly shorter
      median progression-free survival (PFS; 3.5 months, 95% CI: 2.9-4.2) and overall
      survival (OS; 5.8 months, 95% CI: 4.5-7.0) than patients lacking CTC (PFS 10.7
      months, 95% CI: 6.9-14.4, p<0.001; OS 13.3 months, 95% CI: 8.0-18.6, p=0.003).
      Alterations in the marker profile during the course of chemotherapy were not
      predictive of clinical outcome or response to therapy. Yet, a favorable clinical
      response depended significantly on CTC negativity (p=0.03). CONCLUSION: Our data
      suggest that the presence of CTC is a major predictor of outcome in patients with
      gastric and gastroesophageal malignancies.

PMID- 26315109
TI  - Takayasu Arteritis and Pregnancy.
AB  - OBJECTIVE: To assess the relationship between Takayasu arteritis (TAK) and
      pregnancy outcome. METHODS: This study included 240 pregnancies in 96 patients
      fulfilling the American College of Rheumatology 1990 criteria for the
      classification of TAK and/or the 1994 Chapel Hill Consensus Conference
      nomenclature/criteria for vasculitis. We analyzed obstetric and maternal outcomes
      in women who were pregnant before and/or at the same time as or after TAK
      diagnosis. We assessed factors associated with complicated pregnancy. RESULTS:
      One hundred forty-two pregnancies occurred in 52 patients before TAK diagnosis
      (median age at pregnancy 26 years [interquartile range 23-30 years]), and 98
      pregnancies occurred in 52 patients concomitant with or after TAK diagnosis
      (median age at pregnancy 28 years [interquartile range 26-31 years]). Pregnancies
      concomitant with or after TAK diagnosis had a 13-fold higher rate of obstetric
      complications compared to pregnancies before TAK diagnosis (odds ratio 13 [95%
      confidence interval 5-33], P < 0.0001). TAK was associated with a 40% frequency
      of obstetric complications, including preeclampsia/eclampsia (24 pregnancies
      [24%]), premature delivery (8 pregnancies [8%]), and intrauterine fetal growth
      restriction or death (5 pregnancies [5%]). Maternal complications of TAK occurred
      during 39% of pregnancies and included mainly new-onset or worsening hypertension
      (26 pregnancies [27%]). In multivariate analysis, smoking (odds ratio 6.15 [95%
      confidence interval 1.31-28.8]) and disease activity of TAK (a National
      Institutes of Health score of >1) (odds ratio 28.7 [95% confidence interval 7.89
      104.7]) were independently associated with obstetric and maternal complications.
      CONCLUSION: TAK negatively affects pregnancy outcomes. Disease activity increases
      the risk of obstetric and maternal complications, mainly due to arterial
      hypertension.

PMID- 26315110
TI  - Comprehensive molecular pathology analysis of small bowel adenocarcinoma reveals
      novel targets with potential for clinical utility.
AB  - Small bowel accounts for only 0.5% of cancer cases in the US but incidence rates
      have been rising at 2.4% per year over the past decade. One-third of these are
      adenocarcinomas but little is known about their molecular pathology and no
      molecular markers are available for clinical use. Using a retrospective 28
      patient matched normal-tumor cohort, next-generation sequencing, gene expression
      arrays and CpG methylation arrays were used for molecular profiling. Next
      generation sequencing identified novel mutations in IDH1, CDH1, KIT, FGFR2, FLT3,
      NPM1, PTEN, MET, AKT1, RET, NOTCH1 and ERBB4. Array data revealed 17% of CpGs and
      5% of RNA transcripts assayed to be differentially methylated and expressed
      respectively (p < 0.01). Merging gene expression and DNA methylation data
      revealed CHN2 as consistently hypermethylated and downregulated in this disease
      (Spearman -0.71, p < 0.001). Mutations in TP53 which were found in more than half
      of the cohort (15/28) and Kazald1 hypomethylation were both were indicative of
      poor survival (p = 0.03, HR = 3.2 and p = 0.01, HR = 4.9 respectively). By
      integrating high-throughput mutational, gene expression and DNA methylation data,
      this study reveals for the first time the distinct molecular profile of small
      bowel adenocarcinoma and highlights potential clinically exploitable markers. 

PMID- 26315111
TI  - A genome-wide assessment of rare copy number variants in colorectal cancer.
AB  - Colorectal cancer (CRC) is a complex disease with an estimated heritability of
      approximately 35%. However, known CRC-related common single nucleotide
      polymorphisms (SNPs) can only explain ~0.65% of the heritability. This "missing
      heritability" may be explained partially by rare copy number variants (CNVs). In
      this study, we performed a genome-wide scan using Illumina Human-Omni Express
      BeadChip, 694 sporadic CRC cases and 1641 controls were eventually included in
      our analysis after quality control. The global burden analysis revealed a 1.53
      fold excess of rare CNVs in CRC cases compared with controls (P < 1 * 10(-6)),
      and the difference being more pronounced for genic rare CNVs and CNVs overlapped
      with coding regions (1.65-fold and 1.84-fold, respectively, both P < 1 * 10(-6)).
      Interestingly, both the cases in the lowest and middle tertile of age carried a
      higher burden of rare CNVs comparing to the highest tertile. Furthermore, 639 CNV
      disrupted genes exclusive to CRC cases were found to be significantly enriched in
      gene ontology (GO) terms concerning nucleosome assembly and olfactory receptor
      activity. Our study was the first to evaluate the burden of rare CNVs in sporadic
      CRC and suggested that rare CNVs contributed to the missing heritability of CRC.

PMID- 26315112
TI  - HBV preS2 promotes the expression of TAZ via miRNA-338-3p to enhance the
      tumorigenesis of hepatocellular carcinoma.
AB  - Transactivators encoded by HBV, including HBx and preS2, play critical role in
      hepatocellular carcinoma (HCC). YAP, a downstream effector of the Hippo pathway,
      is involved in hepatocarcinogenesis mediated by HBx. Here, we investigated
      whether preS2, another transactivator encoded by HBV, regulates the Hippo pathway
      to promote HCC. We found that preS2 overexpression upregulated TAZ, a downstream
      effector of the Hippo pathway, at protein level but not at mRNA level. preS2
      suppressed miRNA-338-3p expression in HCC cell lines. miRNA-338-3p mimics
      downregulated TAZ, while miRNA-338-3p inhibitor restored the expression of TAZ,
      suggesting that TAZ is a direct target of miRNA-338-3p. TAZ overexpression
      stimulated growth of HCC cell lines. Knockdown of TAZ dampened preS2-promoted HCC
      proliferation and migration. Thus, preS2 upregulates TAZ expression by repressing
      miRNA-338-3p. TAZ is necessary for preS2-promoted HCC proliferation and
      migration. 

PMID- 26315113
TI  - Rituximab-induced HMGB1 release is associated with inhibition of STAT3 activity
      in human diffuse large B-cell lymphoma.
AB  - Treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and
      prednisone (R-CHOP) has greatly improved clinical outcomes in patients with
      diffuse large B-cell lymphoma (DLBCL) compared with CHOP. The mechanism of
      rituximab-induced cell death is poorly understood. We found that rituximab does
      not enhance the directly killing efficacy of CHOP, as tested on a panel of DLBCL
      cell lines. Rituximab induced a rapid release of HMGB1 (High mobility group
      protein B 1). This release is independent of cell death but significantly
      correlated with an inhibition on STAT3 activity. In the resting state, HMGB1 co
      localizes and interacts with STAT3 in the nucleus of DLBCL cells. Treatment with
      rituximab breaks this binding and triggers HMGB1 release. Treatment with R-CHOP
      but not CHOP significantly increased plasma HMGB1 and decreased IL-10
      concentrations in DLBCL patients compared with controls. The conditioned medium
      from rituximab-treated DLBCL cells is able to trigger dendritic cell maturation,
      phagocytosis, and IFN-gamma secretion by cytotoxic T cells. In conclusion, our
      results demonstrate that rituximab induces an inhibition on STAT3 activity,
      leading to increased HMGB1 release and decreased IL-10 secretion, which elicits
      immune responses, suggesting that indirect effects on the immune system rather
      than direct killing contribute to elimination of DLBCL. 

PMID- 26315115
TI  - Preliminary results of a prospective study of inter- and intra-user variability
      of the Royal Veterinary College corneal clarity score (RVC-CCS) for use in
      veterinary practice.
AB  - OBJECTIVE: To introduce a new corneal clarity score for use in small animals and
      describe its inter- and intra-user variability. ANIMALS STUDIED: Twelve dogs and
      two cats with corneal abnormalities and five dogs with healthy corneas. MATERIALS
      AND METHODS: Four examiners scored every patient twice and never consecutively,
      focusing on the central cornea. The peripheral cornea was scored separately. The
      following scoring system was used to describe corneal clarity: G0: no fundus
      reflection is visible on retroillumination (RI) using a head-mounted indirect
      ophthalmoscope. G1: a fundus reflection is visible with RI. G2: a 0.1-mm diameter
      light beam is visible on the anterior surface of the iris and/or lens. G3: gross
      fundic features are visible when viewed with indirect ophthalmoscopy (IO) using a
      head-mounted indirect ophthalmoscope and a hand-held 30D lens, although fine
      details are not clear. G4: fine details of the fundic features are clearly
      visible with IO. The minimum grades given were analyzed for inter- and intra-user
      variability with kappa analysis. RESULTS: Intra- and interuser variability of the
      central corneal clarity ranged from 0.78 to 0.96, showing substantial to almost
      perfect reproducibility, and from 0.66 to 0.91, showing substantial to almost
      perfect reliability, respectively. Intra- and interuser variability of the
      peripheral cornea ranged from 0.83 to 0.95, showing almost perfect agreement, and
      from 0.53 to 0.91, showing moderate to almost perfect agreement. CONCLUSIONS: The
      RVC-CCS is well suited to assess and monitor central corneal clarity in small
      animals and to compare outcomes between studies and different surgeons.

PMID- 26315114
TI  - Elevated S100A9 expression in tumor stroma functions as an early recurrence
      marker for early-stage oral cancer patients through increased tumor cell
      invasion, angiogenesis, macrophage recruitment and interleukin-6 production.
AB  - S100A9 is a calcium-binding protein with two EF-hands and frequently deregulated
      in several cancer types, however, with no clear role in oral cancer. In this
      report, the expression of S100A9 in cancer and adjacent tissues from 79 early
      stage oral cancer patients was detected by immunohistochemical staining. Although
      S100A9 protein was present in both tumor and stromal cells, only the early-stage
      oral cancer patients with high stromal expression had reduced recurrence-free
      survival. High stromal S100A9 expression was also significantly associated with
      non-well differentiation and recurrence. In addition to increasing cell migration
      and invasion, ectopic S100A9 expression in tumor cells promoted xenograft
      tumorigenesis as well as the dominant expression of myeloid cell markers and pro
      inflammatory IL-6. The expression of S100A9 in one stromal component, monocytes,
      stimulated the aggressiveness of co-cultured oral cancer cells. We also detected
      the elevation of serum S100A9 levels in early-stage oral cancer patients of a
      separate cohort of 73 oral cancer patients. The release of S100A9 protein into
      extracellular milieu enhanced tumor cell invasion, transendothelial monocyte
      migration and angiogenic activity. S100A9-mediated release of IL-6 requires the
      crosstalk of tumor cells with monocytes through the activation of NF-kappaB and
      STAT-3. Early-stage oral cancer patients with both high S100A9 expression and
      high CD68+ immune infiltrates in stroma had shortest recurrence-free survival,
      suggesting the use of both S100A9 and CD68 as poor prognostic markers for oral
      cancer. Together, both intracellular and extracellular S100A9 exerts a tumor
      promoting action through the activation of oral cancer cells and their associated
      stroma in oral carcinogenesis. 

PMID- 26315116
TI  - Characterization of the cellular infiltrate in bioprosthetic heart valves
      explanted from patients with structural valve deterioration.

PMID- 26315117
TI  - Evaluation of the Role of IgE Responses to Der p 1 and Der p 2 in Chinese House
      Dust Mite-Allergic Patients.
AB  - BACKGROUND: The role of specific IgE (sIgE) against Der p 1 and Der p 2 in
      Chinese patients with house dust mite (HDM) allergy has not yet been well
      investigated. METHODS: One hundred patients were enrolled, based on sensitization
      and doctor-diagnosed allergy to HDM. Questionnaires were administered to document
      demographic and clinical characteristics. Serum IgE reactivity to
      Dermatophagoides pteronyssinus (Dp) extract, Der p 1, Der p 2 and Der p 10 was
      measured by ImmunoCAP. RESULTS: Almost all patients were sensitized to Der p 1
      (95%) and Der p 2 (93%), with both allergens together being largely responsible
      for the total anti-HDM IgE response. No evidence for a significant role of Der p
      10 was found. Overall, IgE responses to HDM and its 2 major allergens were higher
      in children than in adults in this cross-sectional study. With increasing age,
      IgE responses to Der p 2 become more important. A positive correlation was
      observed between the reaction of sIgE against Dp, Der p 1 and Der p 2 and the
      number of organs (including the eyes, nose, lungs and skin) that were affected in
      patients. CONCLUSIONS: In China, Der p 1 and Der p 2 are the dominant allergens
      in patients with HDM allergy. The relative importance of Der p 1 and Der p 2
      changes with age, in favor of Der p 2. Overall, sIgE titers were positively
      associated with the number of organs affected.

PMID- 26315118
TI  - Facile one-pot formulation of TRAIL-embedded paclitaxel-bound albumin
      nanoparticles for the treatment of pancreatic cancer.
AB  - Nanoparticle albumin-bound (nabTM) technology is an effective way of delivering
      hydrophobic chemotherapeutics. We developed a one-pot/one-step formulation of
      paclitaxel (PTX)-bound albumin nanoparticles with embedded tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL/PTX HSA-NP) for the treatment of
      pancreatic cancer. TRAIL/PTX HSA-NPs were fabricated using a high-pressure
      homogenizer at a TRAIL feeding ratio of 0.2%, 1.0%, and 2.0%. TRAIL/PTX HSA-NPs
      were spherical and became larger in size (170-230 nm) with increasing TRAIL
      amount (0.2-2.0%). The loading efficiencies of PTX were in the range of ~86.4%
      and significantly low at 2.0% TRAIL (60.4%). Specifically, the inhibitory
      concentrations (IC50) of TRAIL (1.0 or 2.0%)/PTX HSA-NPs were >20-fold lower than
      that of plain PTX-HSA NP (0.032+/-0.06, 0.022+/-0.005, and 0.96+/-0.15 ng/ml,
      respectively) in pancreatic Mia Paca-2 cells. Considering TRAIL loading,
      bioactivity, and particle size, TRAIL(1.0%)/PTX HSA-NPs were determined as the
      optimal candidate for further studies. TRAIL(1.0%)/PTX HSA-NPs displayed
      substantially greater apoptotic activity than plain PTX HSA-NP in both FACS and
      TUNEL analysis. The loaded PTX and TRAIL were gradually released from the
      TRAIL(1.0%)/PTX HSA-NPs until ~24 h, which is considered to be a sufficient time
      for delivery to the tumor tissue. TRAIL(1.0%)/PTX HSA-NP displayed markedly more
      antitumor efficacy than plain PTX HSA-NP in Mia Paca-2 cell-xenografted mice in
      terms of tumor volume (size) and weight (213.9 mm(3) and 0.18 g vs. 1126.8 mm(3)
      and 0.80 g, respectively). These improved in vitro and in vivo performances were
      due to the combined synergistic effects of PTX and TRAIL. We believe that this
      TRAIL/PTX HSA-NP would have potential as a novel apoptosis-based anticancer
      agent.

PMID- 26315119
TI  - Effect of milling temperatures on surface area, surface energy and cohesion of
      pharmaceutical powders.
AB  - Particle bulk and surface properties are influenced by the powder processing
      routes. This study demonstrates the effect of milling temperatures on the
      particle surface properties, particularly surface energy and surface area, and
      ultimately on powder cohesion. An active pharmaceutical ingredient (API) of
      industrial relevance (brivanib alaninate, BA) was used to demonstrate the effect
      of two different, but most commonly used milling temperatures (cryogenic vs.
      ambient). The surface energy of powders milled at both cryogenic and room
      temperatures increased with increasing milling cycles. The increase in surface
      energy could be related to the generation of surface amorphous regions. Cohesion
      for both cryogenic and room temperature milled powders was measured and found to
      increase with increasing milling cycles. For cryogenic milling, BA had a surface
      area ~ 5* higher than the one obtained at room temperature. This was due to the
      brittle nature of this compound at cryogenic temperature. By decoupling average
      contributions of surface area and surface energy on cohesion by salinization post
      milling, the average contribution of surface energy on cohesion for powders
      milled at room temperature was 83% and 55% at cryogenic temperature.

PMID- 26315120
TI  - Preparation of olanzapine and methyl-beta-cyclodextrin complexes using a single
      step, organic solvent-free supercritical fluid process: An approach to enhance
      the solubility and dissolution properties.
AB  - The purpose of this study was to evaluate a single-step, organic solvent-free
      supercritical fluid process for the preparation of olanzapine-methyl-beta
      cyclodextrin complexes with an express goal to enhance the dissolution properties
      of olanzapine. The complexes were prepared by supercritical carbon dioxide
      processing, co-evaporation, freeze drying and physical mixing. The prepared
      complexes were then analysed by differential scanning calorimetry, X-ray powder
      diffraction, scanning electron microscopy, solubility and dissolution studies.
      Computational molecular docking studies were performed to study the formation of
      molecular inclusion complexation of olanzapine with methyl-beta-cyclodextrin. All
      the binary mixtures of olanzapine with methyl-beta-cyclodextrin, except physical
      mixture, exhibited a faster and greater extent of drug dissolution than the drug
      alone. Products obtained by the supercritical carbon dioxide processing method
      exhibited the highest apparent drug dissolution. The characterisation by
      different analytical techniques suggests complete complexation or amorphisation
      of olanzapine and methyl-beta-cyclodextrin complexes prepared by supercritical
      carbon dioxide processing method. Therefore, organic solvent-free supercritical
      carbon dioxide processing method proved to be novel and efficient for the
      preparation of solid inclusion complexes of olanzapine with methyl-beta
      cyclodextrin. The preliminary data also suggests that the complexes of olanzapine
      with methyl-beta-cyclodextrin will lead to better therapeutic efficacy due to
      better solubility and dissolution properties. 

PMID- 26315121
TI  - Formulation of a modified-release pregabalin tablet using hot-melt coating with
      glyceryl behenate.
AB  - A modified-release (MR) tablet of the anti-anxiety drug pregabalin (PRE) was
      prepared by hot-melt coating PRE with glyceryl behenate (GB) as a release
      retardant and compressing to form a matrix with microcrystalline cellulose (MCC)
      as a hydrophilic diluent. GB-coated PRE had a size in the range of 177-290 MUm
      with good to acceptable flowability. Tablet hardness decreased slightly as GB
      content increased. PRE release from the tablet matrices was successfully modified
      by altering the ratio of MCC and GB, and it was found that dissolution- or
      diffusion-controlled release depended on the amount of GB used. Drug release was
      pH-independent. An accelerated stability test on the most promising MR tablet at
      40 degrees C and 75% relative humidity for 6 months showed no significant changes
      in PRE content, and the occurrence of total impurities--including PRE-lactam--was
      within acceptable limits. After oral administration of the selected MR tablet or
      a commercial IR capsule (Lyrica) to healthy human volunteers, pharmacokinetic
      parameters including Tmax, Cmax, AUC0-24, and T1/2 were compared. The confidence
      interval of AUC0-24 was within the adequate range, but that of Cmax was
      inadequate. This study demonstrated the potential use of GB for PRE-containing MR
      formulations.

PMID- 26315122
TI  - Mucoadhesive oral films: The potential for unmet needs.
AB  - Oral drug delivery is the most common route of drug administration. Nevertheless,
      there are some important limitations that reinforce the need for developing new
      drug delivery systems. Mucoadhesive oral films (MOF) are promising dosage forms
      that adhere to the oral mucosa and deliver the drug through it, which present
      several advantages. These include: bypassing the hepatic first pass effect, fast
      onset of action, ease of transportation and handling. The use of such dosage form
      is beneficial for drugs that have poor oral bioavailability and also for drugs
      that need to be rapidly absorbed. In spite of the known benefits, the number of
      marketed MOF is still quite small. This review explores the products under
      development and corresponding clinical trials in respect to their status,
      therapeutic indication, companies involved and technologies. In this way, it was
      possible to identify the preferred therapeutic indications, new research and
      market trends as well as future prospects of MOF. Moreover, it is reasonable to
      expect an increase in the number of products on the market due to their great
      potential to satisfy unmet medical needs. 

PMID- 26315123
TI  - Design of lipid microparticle dispersions based on the physicochemical properties
      of the lipid and aqueous phase.
AB  - Lipid microparticle (LMP) dispersions may be utilized as novel pharmaceutical
      dosage forms for different administration routes. The particle size and particle
      size distribution of the LMPs can be classified to the most crucial
      specifications for therapeutical and research applications. The size parameters
      can be adjusted via the physicochemical properties of the inner lipid and the
      outer aqueous phase. In the present study, ten different solid lipids with
      incorporated lecithin and four concentrations of the surfactant poloxamer 407
      (P407) were utilized for LMP dispersion preparation. Physicochemical properties
      of the bulk and dispersed lipid matrices as well as features of the P407
      solutions were determined. Correlations between the mean particle size (mean) of
      the LMPs and the span as parameter for the particle size distribution as
      responses were identified by plotting against the measured physicochemical
      parameters. Most significant linear correlations were found between the mean and
      the micellization onset temperature (Tmicell) in the parent solution and the
      dynamic viscosity of the emulsifier solution at 25  degrees C and between the
      span and the Tmicell in the LMP dispersion. Consequently, P407 micelles as a
      reservoir for surfactant monomers and the overall viscosity as a separator
      between newly-formed lipid droplets are fundamental stabilizing parameters.

PMID- 26315124
TI  - NaCl-triggered self-assembly of hydrophilic poloxamine block copolymers.
AB  - Tetronic 1307 (T1307) is a hydrophilic poloxamine (HLB>24) with a high molecular
      mass owing to its long PEO and PPO blocks. In spite of good biocompatibility, its
      use as a component of drug delivery systems is limited by its high critical
      micelle concentration (CMC) and temperature (CMT). The aim of this work was to
      elucidate whether the addition of NaCl or the combination of salts and
      temperature may bring T1307 micellization and gelling features into more
      practically useful values. Increasing NaCl concentration in the 0.154 M
      (isotonic) to 2M (hypertonic) range made the copolymer more hydrophobic and more
      prone to self-assemble into unimodal micelles, as observed by means of pi-A
      isotherms, (1)H NMR, dynamic light scattering (DLS), small-angle neutron
      scattering (SANS), and pyrene fluorescence. The decrease in CMC and CMT observed
      for T1307 in 0.5 M NaCl medium (tolerable hypertonic solution), compared to
      water, notably favored the solubility of hydrophobic drugs such as curcumin and
      quercetin. Moreover, phase diagram, intrinsic viscosity and sol-to-gel transition
      were markedly affected by NaCl concentration. Overall, the strong dependence of
      T1307 self-assembly features on NaCl opens interesting possibilities for tuning
      the performance of T1307 as a component of nanocarriers and in situ gelling
      systems.

PMID- 26315126
TI  - NiS1.97: A New Efficient Water Oxidation Catalyst for Photoelectrochemical
      Hydrogen Generation.
AB  - NiS1.97, a sulfur-deficient dichalcogenide, in nanoscale form, is shown to be a
      unique and efficient photoelectrochemical (PEC) catalyst for H2 generation by
      water splitting. Phase pure NiS1.97 nanomaterial is obtained by converting nickel
      oxide into sulfide by controlled sulfurization method, which is otherwise
      difficult to establish. The defect states (sulfur vacancies) in this material
      increase the carrier density and in turn lead to favorable band line-up with
      respect to redox potential of water, rendering it to be an effective
      photoelectrochemical catalyst. The material exhibits a remarkable PEC performance
      of 1.25 mA/cm(2) vs NHE at 0.68 V in neutral pH, which is almost 1000 times
      superior as compared with that of the stoichiometric phase of NiS2. The latter is
      well-known to be a cocatalyst but not as a primary PEC catalyst. 

PMID- 26315125
TI  - Protein corona hampers targeting potential of MUC1 aptamer functionalized SN-38
      core-shell nanoparticles.
AB  - Nanoparticles have been considered to improve delivery and physicochemical
      characteristics of bioactive agents in recent years. In this study, a core-shell
      chitosan nanoparticulate system was prepared for the targeted delivery of SN-38.
      SN-38, an active metabolite of camptothecin, conjugated to hyaluronic acid (HA)
      was used as the shell of chitosan nanoparticles decorated with MUC1 aptamer. The
      conjugation was confirmed by UV and (1)H NMR techniques. Targeting efficiency was
      evaluated by confocal microscopy and flow cytometry. It was shown that MUC1
      decoration increased the uptake of nanoparticles by HT29 cells, MUC1 positive
      cell line, while CHO as MUC1 negative cell line showed no enhanced uptake of
      decorated nanoparticles. Compared to non-targeted nanoparticles, flow cytometric
      annexin V/PI analyses showed that the nanoparticles exert cytotoxicity through
      apoptosis. It was, however, shown that protein corona adsorption at the surface
      of nanoparticles hampered the cytotoxicity of nanoparticles, as there was no
      difference between the cytotoxicity of targeted and non-targeted nanoparticles,
      when treated with bovine serum albumin prior to cytotoxicity study. 

PMID- 26315127
TI  - Comparative RNA-seq analysis of the Tritrichomonas foetus PIG30/1 isolate from
      pigs reveals close association with Tritrichomonas foetus BP-4 isolate 'bovine
      genotype'.
AB  - Tritrichomonas foetus was described as a commensal of the stomach, caecum and
      nasal cavity of pigs before it was recognised as the cause of reproductive tract
      disease of cattle. T. foetus also causes chronic large bowel diarrhoea in
      domestic cats. Multi-locus genotyping and comparative transcriptome analysis has
      previously revealed that T. foetus isolated from cat and cattle hosts are
      genetically distinct, referred to as the 'feline genotype' and 'bovine genotype',
      respectively. Conversely, multi-locus genotyping has grouped porcine T. foetus
      with the 'bovine genotype'. To compare the extent of the similarity between
      porcine T. foetus and cattle 'bovine genotype' isolates, RNA-sequencing (RNA-seq)
      was used to produce the first cell-wide transcriptome library of porcine T.
      foetus PIG30/1. Comparative transcriptome analysis of the PIG30/1 with the
      published bovine (BP-4) and feline (G10/1) transcriptomes revealed that the
      porcine T. foetus shares a 4.7 fold greater number of orthologous genes with the
      bovine T. foetus than with the feline T. foetus. Comparing transcription of the
      virulence factors, cysteine proteases (CP) between the three isolates, the
      porcine T. foetus was found to preferentially transcribe CP8 like the 'bovine
      genotype' T. foetus, compared to thehigh transcription of CP7 seen for 'feline
      genotype' T. foetus. At the cell-wide transcriptome level, the porcine T. foetus
      isolate (PIG30/1) groups closer with the 'bovine genotype' T. foetus rather than
      the 'feline genotype' T. foetus. 

PMID- 26315128
TI  - High prevalence of Tritrichomonas foetus 'bovine genotype' in faecal samples from
      domestic pigs at a farm where bovine trichomonosis has not been reported for over
      30 years.
AB  - Bovine venereal trichomonosis caused by the flagellate Tritrichomonas foetus is a
      notifiable disease in Australia. While, T. foetus is pathogenic in both cattle
      and cats, it has long been established that the same T. foetus colonises the
      stomach, caecum and nasal cavity of pigs without apparent clinical significance.
      Multi-locus genotyping grouped the non-pathogenic porcine T. foetus with the
      pathogenic 'bovine genotype', rather than with the 'feline genotype' T. foetus.
      Bovine trichomonosis is now uncommon due to wide-spread use of artificial
      insemination, however, whether T. foetus remains prevalent in pigs where bovine
      trichomonosis has been eradicated remains unknown. We surveyed faecal samples
      from pigs farmed in close proximity with T. foetus-negative cattle. The Modified
      Diamond's Medium assay used were 77.4% (24/31) positive for trichomonads and
      64.50% (20/31) were T. foetus-positive based on real-time PCR and conventional
      PCR. An axenic reference strain of T. foetus, designated PIG30/1 was established.
      In addition, a novel trichomonad ITS rDNA, PIG12, closely related to sequences
      from Trichomitus spp is reported. Multi-locus genotyping at nine loci matched
      PIG30/1 to the 'bovine genotype' T. foetus. In conclusion, cross-species
      transmission of T. foetus between pigs and cows from environmental exposure of T.
      foetus-contaminated pig faeces is unlikely. Domestic T. foetus-positive pigs
      possess a negligible risk of a successful T. foetus transmission event to cattle.

PMID- 26315129
TI  - Charge-tunable indium-organic frameworks built from cationic, anionic, and
      neutral building blocks.
AB  - By using the same ligand, 2,5-furandicarboxylic acid (FDA), and varying synthetic
      conditions (especially the In(3+)/FDA ratio), it is possible to access three
      unique building blocks of indium, demonstrating charge-switching from a positive
      trimer to a negative monomer and leading to the synthesis of In-MOFs with tunable
      framework charge. 

PMID- 26315130
TI  - Outcomes of slit mesh in laparoscopic totally extraperitoneal inguinal hernia
      repair: Does it affect recurrence?
AB  - INTRODUCTION: The aim of this study was to compare outcomes between slit and non
      slit mesh placement in laparoscopic totally extraperitoneal inguinal hernia
      repair. METHODS: This is a retrospective study of 113 patients who underwent
      laparoscopic totally extraperitoneal inguinal hernia repair with Ultrapro mesh
      between January 2010 and December 2011. Sixty-two and 82 hernias were operated on
      in the slit mesh and non-slit mesh groups, respectively. Postoperative
      complications, recurrence, and patient satisfaction levels were evaluated.
      RESULTS: One hernia in the slit mesh group (1/62, 1.6%) and one in the non-slit
      mesh group (1/82, 1.2%) developed recurrence (P = 1.00). The incidence of
      postoperative neuralgia was 4/62 (6.5%) and 7/82 (8.5%) in the slit mesh and non
      slit mesh groups, respectively (P = 0.76). Satisfaction rates in the slit mesh
      and non-slit mesh groups were similar at 60/62 (96.8%) and 80/82 (97.6%),
      respectively (P = 1.00). CONCLUSION: No significant differences in outcomes were
      found between slit and non-slit mesh placement. Both have low complication rates,
      low recurrence rates, and high satisfaction levels.

PMID- 26315131
TI  - CML10, a variant of calmodulin, modulates ascorbic acid synthesis.
AB  - Calmodulins (CaMs) regulate numerous Ca(2+) -mediated cellular processes in
      plants by interacting with their respective downstream effectors. Due to the
      limited number of CaMs, other calcium sensors modulate the regulation of Ca(2+) 
      mediated cellular processes that are not managed by CaMs. Of 50 CaM-like (CML)
      proteins identified in Arabidopsis thaliana, we characterized the function of
      CML10. Yeast two-hybrid screening revealed phosphomannomutase (PMM) as a putative
      interaction partner of CML10. In vitro and in vivo interaction assays were
      performed to analyze the interaction mechanisms of CML10 and PMM. PMM activity
      and the phenotypes of cml10 knock-down mutants were studied to elucidate the
      role(s) of the CML10-PMM interaction. PMM interacted specifically with CML10 in
      the presence of Ca(2+) through its multiple interaction motifs. This interaction
      promoted the activity of PMM. The phenotypes of cml10 knock-down mutants were
      more sensitive to stress conditions than wild-type plants, corresponding with the
      fact that PMM is an enzyme which modulates the biosynthesis of ascorbic acid, an
      antioxidant. The results of this research demonstrate that a calcium sensor,
      CML10, which is an evolutionary variant of CaM, modulates the stress responses in
      Arabidopsis by regulating ascorbic acid production. 

PMID- 26315132
TI  - Body composition and adipokines in patients with juvenile idiopathic arthritis
      and systemic glucocorticoids.
AB  - OBJECTIVES: The aim of this cross-sectional study was to explore body
      composition, and the relationship of serum adipokines with bone mass and disease
      activity, in a cohort of JIA patients with at least three months' exposure to
      systemic glucocorticoids (GC). METHODS: Fifty patients with JIA (34 girls, median
      age 12.4 years and disease duration 6.3 years) and 88 controls matched for gender
      and age participated in this study. Bone mineral content (BMC) and areal bone
      mineral density (BMD) of the lumbar spine and whole body, as well as body
      composition were assessed with dual-energy x-ray absorptiometry. Fasting serum
      leptin and adiponectin were measured. RESULTS: Fat and lean mass were similar
      between patients and controls, but patients had slightly decreased BMD Z-scores.
      Serum leptin and adiponectin concentrations were similar. Disease activity was
      low, and no correlation with adipokines was observed. Patients with bone age
      corrected lumbar spine BMD Z-score <=-1.0 ("low BMD") did not show alterations in
      body composition, GC exposure or current disease activity, but had decreased BMC
      to-lean mass ratio (p<0.001) and tendency for increased serum leptin (p=0.064).
      However, no association of leptin with BMD in multivariate analysis existed in
      patients or controls. An inverse association between adiponectin and whole body
      BMD was observed in both groups. CONCLUSIONS: Normal body composition was
      observed in a JIA cohort with low-dose GC exposure. Patients with "low BMD"
      tended to have increased serum leptin, but leptin did not associate with BMD. In
      this cohort with low disease activity, no correlation between adipokines and
      disease activity was present.

PMID- 26315133
TI  - Screening of non-Ionic Surfactant for Enhancing Biobutanol Production.
AB  - This work deals with finding a suitable non-ionic surfactant which has high
      butanol capturing capacity and can be separated at a temperature close to room
      temperature and does not extract any intermediates or substrate (i.e., glucose).
      Importantly, it should be biocompatible, and its separation from the aqueous
      phase is not affected by other fermentation products. Hence, a pool of non-ionic
      Pluronic surfactants (L31, L61, L62D, L62LF, L62, L81, L92, L101, L121, L64, P65,
      P84, P104, P105) were selected for the study. Screening of the surfactant was
      done based on its hydrophile-lipophile balance (HLB) value, butanol capturing
      capacity (BCC), and cloud point temperature. Among the various surfactant
      investigated, L62D captured maximum amount of butanol (0.68 g/g of surfactant).
      Also, the cloud point temperature of L62D is close to room temperature (28.7 
      degrees C). Biocompatibility studies were carried out by conducting fermentation
      in presence of 3% L62D which resulted in 148% increase in butanol production as
      compared to control (without surfactant). Further, the fermentation products did
      not have strong influence on phase separation.

PMID- 26315134
TI  - Nitrate Starvation Induced Changes in Root System Architecture, Carbon:Nitrogen
      Metabolism, and miRNA Expression in Nitrogen-Responsive Wheat Genotypes.
AB  - Improvement of nutrient use efficiency in cereal crops is highly essential not
      only to reduce the cost of cultivation but also to save the environmental
      pollution, reduce energy consumption for production of these chemical
      fertilizers, improve soil health, and ultimately help in mitigating climate
      change. In the present investigation, we have studied the morphological (with
      special emphasis on root system architecture) and biochemical responses (in terms
      of assay of the key enzymes involved in N assimilation) of two N-responsive wheat
      genotypes, at the seedling stage, under nitrate-optimum and nitrate-starved
      conditions grown in hydroponics. Expression profile of a few known wheat micro
      RNAs (miRNAs) was also studied in the root tissue. Total root size, primary root
      length, and first- and second-order lateral root numbers responded significantly
      under nitrate-starved condition. Morphological parameters in terms of root and
      shoot length and fresh and dry weight of roots and shoots have also been observed
      to be significant between N-optimum and N-starved condition for each genotypes.
      Nitrate reductase (NR), glutamine synthatase (GS), and glutamate dehydrogenase
      (GDH) activity significantly decreased under N-starved condition. Glutamine
      oxoglutarate amino transferase (GOGAT) and pyruvate kinase (PK) activity was
      found to be genotype dependent. Most of the selected miRNAs were expressed in
      root tissues, and some of them showed their differential N-responsive expression.
      Our studies indicate that one of the N-responsive genotype (NP-890) did not get
      affected significantly under nitrogen starvation at seedling stage. 

PMID- 26315135
TI  - Switching properties of Li-benzene complexes in a uniform electric field: a case
      where a "small" change makes a big difference.
AB  - The effect of a homogeneous static electric field on the Li-benzene complex in
      two configurations, one with a larger Li-C6H6 distance ("loose") and one with a
      shorter distance ("tight"), has been investigated. The electric field has the
      same orientation as the direction of the dipole moments of the complexes. When
      the direction of the field intensity vector was the same as that of the dipole
      moment vector, optimization of the complex's geometry in one configuration
      resulted in switching it to the other one. Reversing the direction of the field
      then transformed the other configuration back to the original one. This switching
      behavior was observed beginning with the loose configuration and with the tight
      configuration. The geometrical and electronic parameters of the complex after
      four steps of the reversible switching have been calculated for a selected field
      intensity of 0.005 atomic units (a.u.), that is 0.257 V A(-1). 

PMID- 26315136
TI  - A small-world network model of facial emotion recognition.
AB  - Various models have been proposed to increase understanding of the cognitive
      basis of facial emotions. Despite those efforts, interactions between facial
      emotions have received minimal attention. If collective behaviours relating to
      each facial emotion in the comprehensive cognitive system could be assumed,
      specific facial emotion relationship patterns might emerge. In this study, we
      demonstrate that the frameworks of complex networks can effectively capture those
      patterns. We generate 81 facial emotion images (6 prototypes and 75 morphs) and
      then ask participants to rate degrees of similarity in 3240 facial emotion pairs
      in a paired comparison task. A facial emotion network constructed on the basis of
      similarity clearly forms a small-world network, which features an extremely short
      average network distance and close connectivity. Further, even if two facial
      emotions have opposing valences, they are connected within only two steps. In
      addition, we show that intermediary morphs are crucial for maintaining full
      network integration, whereas prototypes are not at all important. These results
      suggest the existence of collective behaviours in the cognitive systems of facial
      emotions and also describe why people can efficiently recognize facial emotions
      in terms of information transmission and propagation. For comparison, we
      construct three simulated networks--one based on the categorical model, one based
      on the dimensional model, and one random network. The results reveal that small
      world connectivity in facial emotion networks is apparently different from those
      networks, suggesting that a small-world network is the most suitable model for
      capturing the cognitive basis of facial emotions.

PMID- 26315137
TI  - Controlled Light-Mediated Preparation of Gold Nanoparticles by a Norrish Type I
      Reaction of Photoactive Polymers.
AB  - Gold nanoparticles (AuNPs) are subjects of broad interest in scientific community
      due to their promising physicochemical properties. Herein we report the facile
      and controlled light-mediated preparation of gold nanoparticles through a Norrish
      type I reaction of photoactive polymers. These carefully designed polymers act as
      reagents for the photochemical reduction of gold ions, as well as stabilizers for
      the in situ generated AuNPs. Manipulating the length and composition of the
      photoactive polymers allows for control of AuNP size. Nanoparticle diameter can
      be controlled from 1.5 nm to 9.6 nm.

PMID- 26315138
TI  - Roles of Toll-like Receptor 7 and 8 in Prevention of Intrauterine Transmission of
      Hepatitis B Virus.
AB  - BACKGROUND: Approximately 5% of newborns were infected by hepatitis B virus (HBV)
      via intrauterine transmission, but most of the infants born to HBV-positive
      mothers are protected from infection. However, the mechanisms by which
      intrauterine transmission is avoided remain elusive, and the roles of toll-like
      receptors (TLRs) have been proposed. The aims of this study were to clarify if
      TLR 7 and 8 are involved in the prevention of intrauterine transmission of HBV.
      METHODS: Real time polymerase-chain reaction (PCR) was used to determine the
      expression of TLRs and cytokines in placenta and trophoblasts. The expression of
      MyD88 was interfered with small interfering RNA (siRNA) in trophoblasts. An in
      intro model mimicking trophoblast barrier was established to evaluate the effect
      of MyD88 siRNA on HBV transmission across trophoblast barrier. RESULTS: There
      were significant differences in placental expression of TLR7 (F=3.263, P=0.048)
      and TLR8 (F=3.257, P=0.048) among control (HBV-negative women), non-infected
      group (HBV-positive women whose infants were not infected) and infected group
      (HBV-positive women whose infants were infected). The expression of TLR7 was
      significantly higher in non-infected group than infected group (P=0.039) and
      control (P=0.043). There was a significant difference in TLR8 expression between
      non-infected group and control (P=0.014), and the difference was close to but not
      significant (P=0.074) between non-infected and infected groups. Exposure of
      trophoblast to HBV significantly induced the expression of TLR7 (P<0.001), TLR8
      (P=0.005), MyD88 (P=0.004), interferon (IFN)-alpha (P=0.004), IFN-beta (P<0.001)
      and interleukin (IL)-8 (P=0.001). When MyD88 was interfered by siRNA, the
      expression of IFN-alpha (P<0.001), IFN-beta (P=0.01) and IL-8 (P<0.001) was
      significantly decreased while the amount of HBV transcytosed across trophoblastic
      barrier significantly increased (P=0.03). CONCLUSIONS: TLR7 and TLR8 on
      trophoblastic cells play an important role in the prevention of intrauterine HBV
      transmission by inhibiting HBV translocation across trophoblast.

PMID- 26315140
TI  - Synchronous parotid and nasopharyngeal Warthin tumor.
AB  - BACKGROUND: Warthin tumor is the second most common benign salivary gland
      neoplasm after pleomorphic adenoma. Warthin tumors occur almost exclusively in
      the parotid gland and periparotid lymph nodes, extraparotid localization is rare.
      METHODS AND RESULTS: We describe a case of a patient presenting with a
      synchronous unilateral parotid gland and nasopharyngeal Warthin tumor.
      CONCLUSION: We propose that, although this occurrence of a synchronous parotid
      gland and nasopharyngeal Warthin tumor may be coincidental, it is more likely to
      be an effect of a systemic factor.

PMID- 26315139
TI  - Infectivity and insertional mutagenesis of endogenous retrovirus in autoimmune
      NZB and B/W mice.
AB  - Murine leukaemia virus has been suggested to contribute to both autoimmune
      disease and leukaemia in the NZB mouse and in the (NZB * NZW) F1 (abbreviated
      B/W) mouse. However, with apparently only xenotropic but no ecotropic virus
      constitutively expressed in these mice, few mechanisms could explain the
      aetiology of either disease in either mouse strain. Because pseudotyped and/or
      inducible ecotropic virus may play a role, we surveyed the ability of murine
      leukaemia virus in NZB, NZW and B/W mice to infect and form a provirus. From the
      spleen of NZB mice, we isolated circular cDNA of xenotropic and polytropic virus,
      which indicates ongoing infection by these viruses. From a B/W lymphoma, we
      isolated and determined the complete sequence of a putative ecotropic NZW virus.
      From B/W mice, we recovered de novo endogenous retroviral integration sites
      (tags) from the hyperproliferating cells of the spleen and the peritoneum. The
      tagged genes seemed to be selected to aid cellular proliferation, as several of
      them are known cancer genes. The insertions are consistent with the idea that
      endogenous retrovirus contributes to B-cell hyperproliferation and progression to
      lymphoma in B/W mice. 

PMID- 26315141
TI  - The role of placenta-derived mesenchymal stem cells in healing of induced full
      thickness skin wound in a mouse model.
AB  - We examined the effect of placenta-derived MSCs (PDMSCs) injection
      intraregionally and intraperitoneally on healing of induced full thickness mice
      skin wounds; moreover, the mechanisms by which MSCs exert their effects were also
      studied. Sixty female mice were divided into three groups after induction of full
      thickness skin wound; untreated group, wounded mice were injected with MSCs
      derived from human placenta intraperitoneally or intraregionally. Skin biopsies
      were obtained 7 and 12 days after wound incision for histological examinations,
      detection of vascular endothelial growth factor (VEGF) by ELISA, and estimation
      of expression of mouse ICAM-1, Integrin beta1, Integrin beta3 genes and human
      albumin and GAPDH genes by reverse transcription polymerase chain reaction. Human
      placenta derived-MSCs treated groups showed accelerated wound healing than non
      treated group. VEGF, Integrin beta1, and Integrin beta3 levels were significantly
      increased in the intraregionally and intraperitoneally treated mice as compared
      to non-treated group at day 7 after wound induction. ICAM-1 showed significant
      decrease in its expression in treated groups compared with non-treated group.
      Interestingly, the intraperitoneal MSCs injections showed better results than
      intraregional one. PDMSCs accelerate full thickness skin wound healing and the
      intraperitoneal MSCs injections are more effective than intraregional one. MSCs
      promote wound healing through release of proangiogenic factors as VEGF, increase
      healing promoting factors as integrin beta1 and beta3, and decrease
      proinflammatory cytokines as ICAM-1.

PMID- 26315142
TI  - Dipolar SAMs Reduce Charge Carrier Injection Barriers in n-Channel Organic Field
      Effect Transistors.
AB  - In this work we examine small conjugated molecules bearing a thiol headgroup as
      self assembled monolayers (SAM). Functional groups in the SAM-active molecule
      shift the work function of gold to n-channel semiconductor regimes and improve
      the wettability of the surface. We examine the effect of the presence of
      methylene linkers on the orientation of the molecule within the SAM. 3,4,5
      Trimethoxythiophenol (TMP-SH) and 3,4,5-trimethoxybenzylthiol (TMP-CH2-SH) were
      first subjected to computational analysis, predicting work function shifts of 
      430 and -310 meV. Contact angle measurements show an increase in the wetting
      envelope compared to that of pristine gold. Infrared (IR) measurements show tilt
      angles of 22 and 63 degrees , with the methylene-linked molecule (TMP-CH2-SH)
      attaining a flatter orientation. The actual work function shift as measured with
      photoemission spectroscopy (XPS/UPS) is even larger, -600 and -430 meV,
      respectively. The contact resistance between gold electrodes and poly[N,N'-bis(2
      octyldodecyl)-naphthalene-1,4:5,8-bis(dicarboximide)-2,6-diyl]-alt-5,5'-(2,2'
      bithiophene) (Polyera Aktive Ink, N2200) in n-type OFETs is demonstrated to
      decrease by 3 orders of magnitude due to the use of TMP-SH and TMP-CH2-SH. The
      effective mobility was enhanced by two orders of magnitude, significantly
      decreasing the contact resistance to match the mobilities reported for N2200 with
      optimized electrodes. 

PMID- 26315143
TI  - Coping-Infused Dialogue through Patient-Preferred Live Music: A Medical Music
      Therapy Protocol and Randomized Pilot Study for Hospitalized Organ Transplant
      Patients.
AB  - BACKGROUND: Solid organ transplant patients often experience a variety of
      psychosocial stressors that can lead to distress and may hinder successful
      recovery. Using coping-infused dialogue (CID) through patient- preferred live
      music (PPLM) music therapy sessions may improve mood and decrease pain while also
      imparting psychoeducational knowledge concerning the identification of local and
      global problems and coping skills. OBJECTIVE: The purpose of this pilot study was
      to develop a coping-based medical music therapy protocol that combines coping
      infused dialogue (CID) with patient-preferred live music (PPLM) and measure the
      effects of the resulting CID-PPLM protocol on mood (positive and negative affect)
      and pain in hospitalized transplant patients. METHODS: Our study used a pre
      /posttest single-session wait-list control design. Participants (N=25) were
      randomly assigned to experimental (CID-PPLM) or control (usual care) conditions.
      Participants in the CID-PPLM condition received a single 30-minute session that
      integrated stressor identification and knowledge of coping skills (CID) with
      patient-preferred live music (PPLM). RESULTS: Results indicated no between-group
      differences at pretest and significant correlations between pre- and posttest
      measures. Concerning posttest ANCOVA analyses, there were significant between
      group differences in positive affect, negative affect, and pain, with
      experimental participants having more favorable posttest scores than control
      participants. Effect sizes were in the medium-to-large range for positive affect
      (eta2=.198), negative affect (eta2=.422), and pain (eta2=.303). CONCLUSIONS: CID
      through receptive PPLM may be an effective protocol for improving mood and
      decreasing pain in organ transplant recipients. MT interventions can be an
      important tool to develop rapport and enhance outcomes with patients. As greater
      engagement during interventions may have stronger treatment effects, we recommend
      future research examining patient engagement as a potential mediator of
      intervention effects, as well as the number of sessions required to maximize
      clinical outcomes.

PMID- 26315144
TI  - Systems Approach to targeted and long-acting HIV/AIDS therapy.
AB  - Medication adherence and insufficient drug levels are central to HIV/AIDS disease
      progression. Recently, Fletcher et al. confirmed that HIV patients on oral
      antiretroviral therapy had lower intracellular drug concentrations in lymph nodes
      than in blood. For instance, in the same patient, multiple lymph node drug
      concentrations were as much as 99 % lower than in blood. This study built upon
      our previous finding that HIV patients taking oral indinavir had 3-fold lower
      mononuclear cell drug concentrations in lymph nodes than in blood. As a result,
      an association between insufficient lymph node drug concentrations in cells and
      persistent viral replication has now been validated. Lymph node cells,
      particularly CD4 T lymphocytes, host HIV infection and persistence; CD4 T cell
      depletion in blood correlates with AIDS progression. With established drug
      targets to overcome drug insufficiency in lymphoid cells and tissues, we have
      developed and employed a "Systems Approach" to engineer multi-drug-incorporated
      particles for HIV treatment. The goal is to improve lymphatic HIV drug exposure
      to eliminate HIV drug insufficiency and disease progression. We found that nano
      particulate drugs that absorb, transit, and retain in the lymphatic system after
      subcutaneous dosing improve intracellular lymphatic drug exposure and overcome
      HIV lymphatic drug insufficiency. The composition, physical properties, and
      stability of the drug nanoparticles contribute to the prolonged and enhanced drug
      exposure in lymphoid cells and tissues. In addition to overcoming lymphatic drug
      insufficiency and potentially reversing HIV infection, targeted drug nanoparticle
      properties may extend drug concentrations and enable the development of long
      acting HIV drug therapy for enhanced patient compliance. 

PMID- 26315145
TI  - Identification, characterization and immunological analysis of Ras related C3
      botulinum toxin substrate 1 (Rac1) from grass carp Ctenopharyngodon idella.
AB  - Rac1, a Rho GTPase, serves critical immunological functions in mammals. Here, a
      Rac1 homolog (gcRac1) was identified in grass carp (Ctenopharyngodon idella). The
      full-length 2023-base pair gcRac1 cDNA contained a 579-bp open reading frame
      encoding a 192-residue protein, including a conserved RHO domain and nuclear
      localization signal. The gcRac1 protein shares high identity with other Rac1
      counterparts and phylogenetically clustered with Danio rerio Rac1. The gcRac1
      transcript showed wide tissue distribution and was inducible by Aeromonas
      hydrophila in vivo and in vitro; its expression also fluctuated with LPS or
      flagellin stimulation in vitro. With gcRac1 over-expression, gcPAK1, gcIL1-beta,
      gcTNF-alpha and gcIFN were basically up-regulated by A. hydrophila and bacterial
      PAMPs induction, while gcRac1 knockdown decreased these transcripts after A.
      hydrophila challenge. Over-expression of gcRac1 reduced, while its suppression
      facilitated, bacterial invasion. Moreover, gcRac1 could activate NF-kappaB
      signaling. These findings implicate the vital role of gcRac1 in grass carp innate
      immunity. 

PMID- 26315146
TI  - Expert's comment concerning "Chest wall reconstruction after en bloc Pancoast
      tumor resection with the use of MatrixRib and SILC Fixation systems: technical
      note" (Marcin Czyz, Emmanuel Addae-Boateng, Bronek M. Boszczyk): Update in
      Pancoast Tobias en bloc resections.

PMID- 26315147
TI  - Limited Self-control, Obesity, and the Loss of Happiness.
AB  - Is obesity the consequence of an optimally chosen lifestyle or do people consume
      too much relative to their long-term preferences? The latter perspective accepts
      that people might face self-control problems when exposed to the immediate
      gratification from food. We exploit unique survey data for Switzerland in
      multinomial logit and ordered probit regressions to study (i) the covariates of
      obesity including indicators of self-control and (ii) the consequences of obesity
      on the subjective well-being of people with limited willpower. Our main finding
      is that obesity decreases the well-being of individuals who report having limited
      self-control, but not otherwise. (c) 2015 John Wiley & Sons, Ltd.

PMID- 26315148
TI  - Pregnancy course in patients with intrahepatic cholestasis of pregnancy treated
      with very low doses of ursodeoxycholic acid.

PMID- 26315149
TI  - Prevalence of Anti-Citrullinated Protein Antibodies and IgM Rheumatoid Factor in
      First-Degree Relatives of Dutch Rheumatoid Arthritis Patients.

PMID- 26315150
TI  - Abattoir surveillance demonstrates contagious bovine pleuropneumonia is
      widespread in Tanzania.
AB  - A study was conducted to investigate the presence of contagious bovine
      pleuropneumonia (CBPP) in the slaughter facilities in 10 regions of Tanzania that
      reported pathological lesions suggestive of CBPP during meat inspection. The aim
      was to ascertain if slaughter facilities can be used to monitor the occurrence
      and spread of CBPP in the country. The study involved a questionnaire survey,
      clinical examination of animals for CBPP symptoms prior to slaughter and
      postmortem examination of the respiratory system in slaughtered cattle. A total
      of 12 slaughterhouses and 31 animal markets were involved in the study. A total
      of 2736 cattle were slaughtered comprising 1978 and 758 in slaughterhouses and
      animal markets, respectively. Of the total slaughtered stock, 351 of 2736 (12.8
      %) had lesions suggestive of CBPP and of these, 236 (8.6 %) were from
      slaughterhouses and 115 (4.2 %) from animal markets. Acute CBPP cases were
      observed in 192 of the 236 (81.4 %) and 71 of the 115 (61.7 %) of the animals
      inspected in the slaughterhouses and markets, respectively. Chronic cases were
      encountered in 24 (10.2 %) of the animals slaughtered in the slaughterhouses and
      19 (16.5 %) at animal markets. This work has confirmed that targeted monitoring
      for CBPP lesions through meat inspection can be a useful tool for CBPP
      surveillance in endemic countries like Tanzania. 

PMID- 26315151
TI  - Serological and molecular survey of sheep infected with Mycoplasma ovipneumoniae
      in Xinjiang, China.
AB  - Mycoplasma pneumonia is one of the most important infectious diseases that
      threaten sheep production. In order to investigate the epidemic status of
      Mycoplasma ovipneumoniae infection in sheep, indirect hemagglutination assay was
      used to analyze 1679 serum samples collected from four different breeds of sheep
      (Kazak sheep, Hu sheep, Merino sheep, and Duolang sheep) in six regions in
      Xinjiang between 2012 and 2014. One thousand one hundred sixty-nine sheep nasal
      swabs and 180 lungs were PCR analyzed. The results showed that the average
      positive rates of the serum samples were 17.75 %. The positive rates were between
      9.76 and 30.61 % in the four breeds. Among them, the Hu sheep had a significantly
      higher rate than other breeds (P < 0.05). The average positive rates of nasal
      swabs and lungs were 10.18 and 28.89 %, respectively. Based on the phylogenetic
      trees of 16S RNA gene, the isolates were closest to those strains isolated from
      inland areas of China, indicating that these epidemic isolates came from the
      trans-province introductions. Our survey suggests that quarantine is necessary
      for sheep imported from inland, and effective immunization should be implemented
      in sheep susceptible to M. ovipneumoniae in Xinjiang, China. 

PMID- 26315152
TI  - Earlier intensified insulin treatment of Type 1 diabetes and its association with
      long-term macrovascular and renal complications.
AB  - AIMS: To investigate the incidence of all-cause mortality, composite mortality
      and morbidity in people with Type 1 diabetes formerly randomized in the Stockholm
      Diabetes Intervention Study. METHODS: A total of 102 people with Type 1 diabetes
      were randomized in the period 1982-1984 to intensified conventional treatment or
      standard treatment with insulin for a mean of 7.5 years. We prospectively re
      evaluated this cohort for the period until 2011 with regard to all-cause
      mortality and composite mortality, which consisted of myocardial infarction,
      stroke and end-stage renal disease as primary endpoints. Secondary endpoints were
      first-time hospitalization for myocardial infarction and stroke or end-stage
      renal disease. Data on HbA1c levels (mean of 22 values/person) were
      retrospectively collected between 1996 and 2011. RESULTS: During the median
      follow-up of 28 years, 22 people died: seven in the intensified conventional
      insulin group compared with 15 in the standard treatment group (P = 0.30). With
      regard to composite mortality, six people in the intensified conventional insulin
      group died compared with 11 in the standard treatment group (P = 0.56). For the
      secondary endpoints, 11 people in the intensified conventional insulin group
      developed myocardial infarction or stroke compared with 17 in the standard
      treatment group (P = 0.72), and one person in the intensified conventional
      insulin compared with seven people in the standard treatment group developed end
      stage renal disease (P = 0.09). Mean HbA1c levels did not differ between groups
      during the follow-up years. CONCLUSIONS: All-cause mortality, cardiovascular
      morbidity and progression to end-stage renal disease did not differ in people
      with Type 1 diabetes earlier randomized to intensified insulin treatment.

PMID- 26315153
TI  - Historical perspectives: a snapshot of women admitted to psychiatric facilities
      with psychosis or mania after childbirth in the late Victorian and inter-war
      periods.
AB  - AIM: This study analysed historical healthcare records to investigate how women
      diagnosed with mania or psychosis and admitted to two mental health facilities in
      Australia following childbirth, were described in the late Victorian (1885-1895)
      and inter-war period (1925-1935). BACKGROUND: Although historians have examined
      the history of mental health systems in Australia, there is no published
      scholarship that considers the healthcare records of these women. This was a
      unique opportunity to explore these documents. DESIGN: An historical study
      examining healthcare records. The data collection occurred in 2012. METHODS:
      Women admitted to mental health facilities with a diagnosis of psychosis or mania
      were identified in the admission registers found in the State Record Office of
      New South Wales and, if available, their healthcare record was transcribed
      verbatim. The records were imported into NVivo 10 for content analysis to
      determine the range and scope of information. A further textual analysis was
      conducted to see if the woman's diagnosis was congruent with the outcome of her
      admission. RESULTS/FINDINGS: 155 cases were identified across the two periods.
      Although, demographic data and the description of the women on admission were
      remarkably similar, 17% of women were physically, rather than mentally, ill and
      died soon after admission. The findings demonstrate the importance of current
      practices such as taking a comprehensive healthcare assessment and the use of
      antibiotics and sanitary measures during labour and in the postnatal period.
      CONCLUSION: Historical investigations of healthcare records provide legitimacy
      for current healthcare practices.

PMID- 26315154
TI  - Minimizing right ventricular pacing in pacemaker patients with intact and
      compromised atrioventricular conduction : Results from the EVITA Trial.
AB  - INTRODUCTION: Unnecessary ventricular pacing is associated with increased
      morbidity and mortality. Over the years different algorithms have been developed
      to reduce right ventricular pacing. OBJECTIVES: Goal of the present study was to
      test the efficacy of the ventricular intrinsic preference (VIP) algorithm in
      patients with atrioventricular intact (AVi) and atrioventricular compromised
      (AVc) AV-conduction. METHODS: Evaluation of VIP feature in pacemaker patients
      (EVITA) was a multicenter, prospective, randomized trial (Trials.gov Identifier:
      NCT00366158). In total, 389 patients were randomized to AVc group: n = 140/132
      VIP OFF/VIP On, AVi group: n = 54/63 VIP OFF/VIP ON). One-month post-implantation
      AV conduction testing (AVc: PR/AR interval > 210 ms) was performed. Follow-up
      visits occurred 6 and 12 months after DDD-pacemaker implantation. RESULTS: In AVi
      and AVc-patients initiation of the VIP feature significantly reduced incidence of
      ventricular pacing (AVi: 53 +/- 38 vs. 9 +/- 21%, p = 0.0001; AVc: 79 +/- 31 vs.
      28 +/- 35%, p = 0.0001). DDD-pacemaker implantation per se significantly reduced
      incidence of AF in VIP ON (AVi 27 vs. 0%, p < 0.0001; AVc 29 vs. 3%, p < 0.0001)
      and VIP OFF patients (AVi 43 vs. 4%, p < 0.0001; AVc 33 vs. 3, p < 0.0001),
      without significant differences between VIP ON and OFF groups (p > 0.05). In the
      AVc group activation of VIP significantly reduced incidence of adverse events
      (AE). All-cause mortality was not significantly different in VIP ON (n = 5) and
      VIP OFF (n = 4, p > 0.05) patients. CONCLUSION: AV search hysteresis (VIP)
      markedly reduces ventricular pacing both in patients with normal AV conduction
      and in patients with prolonged PR interval or intermittent AV block.

PMID- 26315155
TI  - Manipulating aggregation and molecular orientation in all-polymer photovoltaic
      cells.
AB  - Manipulating molecular orientation at the donor/acceptor interface is the key to
      boosting charge separation properties and efficiencies of anisotropic-materials
      based organic photovoltaics (OPVs). By replacing the polymeric donor PBDTBDD with
      its 2D-conjugated polymer PBDTBDD-T, the power conversion efficiency of OPVs
      featuring the anisotropic polymer acceptor PNDI is drastically boosted from 2.4%
      up to 5.8%. 

PMID- 26315157
TI  - Professional regulation--incoherent, expensive and ineffective.

PMID- 26315156
TI  - Temperament and its Association with Autism Symptoms in a High-risk Population.
AB  - Temperament was investigated in a group of high-risk infants (N = 383; 45 %
      girls) who had an older sibling with autism spectrum disorder (ASD), and in
      community control infants (N = 162; 46 % girls) with no family history of ASD
      (low-risk). The infants were assessed at age 12 months using the Infant Behavior
      Questionnaire, and at 24 months using the Toddler Behavior Assessment
      Questionnaire. At 36 months, an independent blind diagnostic assessment for ASD
      was conducted using the Autism Diagnostic Interview-Revised (ADI-R) and the
      Autism Diagnostic Observation Schedule (ADOS). The results indicate not only
      differences in temperament traits between the high- and low-risk groups, but also
      differences in the structure of higher-order temperament factors. The results
      support the importance of early reactive temperament in the development of
      Effortful Control in the high-risk sample. Furthermore, Effortful Control at 24
      months appears to play a critical role in predicting later ASD symptoms (at 36
      months). Taken together, these findings support the use of early temperament as
      an endophenotype for ASD. 

PMID- 26315158
TI  - A tribute to the king.

PMID- 26315159
TI  - Prison dentistry: Irish prisoners' oral health.

PMID- 26315160
TI  - Case report: Getting it taped.

PMID- 26315161
TI  - Oral cancer: Cancer referral guidelines.

PMID- 26315162
TI  - In surgery: An observation on an observation.

PMID- 26315163
TI  - Publishing: Predatory publishing.

PMID- 26315164
TI  - Feature: Getting the mix right.

PMID- 26315166
TI  - Dental profession takes a lead on antibiotic resistance.

PMID- 26315167
TI  - BDJ World War I cover series prints.

PMID- 26315168
TI  - A result for dentistry in West Midlands as BDA and LDC unite on minor oral
      surgery.

PMID- 26315169
TI  - Calls for smoking ban to be extended.

PMID- 26315170
TI  - From the archive: Now and then.

PMID- 26315173
TI  - Jeremy Rees: 'We need to make people more aware of the issues relating to acid
      erosion'.
AB  - Jeremy Rees is Professor of Restorative Dentistry at Cardiff University. Jeremy
      is also the director of Cardiff's M Clin Dent programme. His research interests
      include biomechanics, erosion, dentine sensitivity and tooth whitening. 

PMID- 26315174
TI  - Clinical research in primary dental care.
AB  - Many commissioning bodies for research expect that researchers will actively
      involve the public and patients in their projects. The National Institute for
      Health Research (NIHR), for example, involves members of the public in reviewing
      funding applications and making recommendations about research funding. The
      NIHR's portfolio is currently operating in 97% of NHS Trusts and this now
      includes research sited in primary dental care. This paper presents some case
      studies of these and other projects which are designed specifically for patient
      benefit in dental services in the community. This means there is no necessity to
      translate the outcomes of such research from a university or hospital base to the
      general population as the projects are undertaken in dental practices that
      provide primary dental care to (predominantly) NHS patients. The relevance of the
      outcomes to dental care is, therefore, likely to be of direct interest and
      importance to commissioners of healthcare funding in the UK who have a duty to
      use evidence bases for commissioning decisions.

PMID- 26315179
TI  - The use of a mobile app to motivate evidence-based oral hygiene behaviour.

PMID- 26315180
TI  - A multivariate statistical analysis on variables affecting inferior alveolar
      nerve damage during third molar surgery.

PMID- 26315181
TI  - Dental students' perceptions of their experience at a residential outreach
      centre.
AB  - INTRODUCTION: The Portsmouth Dental Academy delivers an interprofessional
      education to dental students on outreach placement from King's College London
      Dental Institute. AIM: To establish what the dental students' attitudes to the
      placement are and how these correlate to the perceptions of the staff who work
      with them. METHOD: Using Delphi consensus procedures, a simple, closed, two
      question questionnaire was developed. The questionnaire was completed by the
      students and then, to triangulate the results, was subsequently applied to staff
      who teach and assist them on clinic. RESULTS: To the question: Why do you think
      the experience that is commonly termed the 'Portsmouth experience' is so
      successful 'in the eyes of the students'?, the students ranked first the
      response: 'Students gain experience in primary dental care clinical practice
      under the current NHS contract - UDAs and KPIs'. To the second question: What do
      you think the students most enjoyed about working in Portsmouth?, the students
      ranked first: 'A sense of independence - being made to make their own decisions'.
      CONCLUSION: The students' major perception of the 'Portsmouth experience' centres
      around the placement being a realistic preparation for their future practising
      career. This is combined with a strong sense of belonging when studying and
      working at the Academy.

PMID- 26315182
TI  - A qualitative evaluation of foundation dentists' and training programme
      directors' perceptions of clinical audit in general dental practice.
AB  - This study reports on an investigation into clinical audit (CA) educational and
      service delivery outcomes in a dental foundation training (DFT) programme. The
      aim was to investigate CA teaching, learning and practice from the perspective of
      foundation dentists (FDs) and to record suggestions for improvement. A
      qualitative research methodology was used. Audio recordings of focus group
      interviews with FDs were triangulated by an interview with a group of training
      programme directors (TPDs). The interviews were transcribed and thematically
      analysed using a 'Framework' approach within Nvivo Data Analysis Software. FDs
      report considerable learning and behaviour change. However, TPDs have doubts
      about the long-term effects on service delivery. There can be substantial
      learning in the clinical, managerial, communication and professionalism domains,
      and in the development of time management, organisational and team-working
      skills. Information is provided about use of resources and interaction with
      teachers and colleagues. CA provides learning opportunities not produced by other
      educational activities including 'awkward conversations' with team-members in the
      context of change management and providing feedback. This is relevant when
      applying the recommendations of the Francis report. This paper should be useful
      to any dentist conducting audit or team training. Suggestions are made for
      improvements to resources and support including right touch intervention.
      Trainers should teach in the 'Goldilocks Zone'.

PMID- 26315183
TI  - The impact of dental phobia on patient consent.
AB  - Dental anxiety is prevalent across a broad spectrum of the population. Dental
      phobia is extreme dental fear, which interferes with normal functioning. For any
      dental treatment, it is an ethical, legal and professional duty of dentists to
      obtain valid informed consent from their patients. The question arises as to how
      dental phobia impacts on patients' ability to give valid informed consent.
      Extreme fear may impair patient ability to understand information about the
      procedure, their capacity to make balanced decisions, and to make these decisions
      voluntarily. A trusting rapport between dentist and patient, supporting patient
      understanding by providing useful information material, and keeping regular
      appointments, may help overcome these obstacles. Other factors impacting on the
      informed consent process are institutional in nature. Implementing ways to
      overcome these is part of the dentist's duty to obtain valid consent. 

PMID- 26315196
TI  - The use of a mobile app to motivate evidence-based oral hygiene behaviour.
AB  - INTRODUCTION: Mobile apps are software programmes that run on smartphones and
      other mobile devices. Mobile health apps can help people manage their own health
      and wellness, promote healthy living and gain access to useful information when
      and where they need it. The Brush DJ oral health app was developed to use the
      opportunity mobile apps offer to motivate an evidence-based oral hygiene routine.
      A literature review has found no research investigating the use of a mobile app
      to motivate evidence-based oral hygiene behaviour. OBJECTIVE: The objective of
      this preliminary investigation was to assess user perception of an oral health
      app to give a basis for future research and development of app technology in
      relation to oral health. METHOD: A cross-sectional qualitative user perception
      questionnaire.RESULTS :One hundred and eighty-nine people responded to the
      questionnaire. Seventy percent (n = 113) of respondents reported that their teeth
      felt cleaner since using the app. Eighty-eight percent (n = 133) reported the app
      motivated them to brush their teeth for longer and 92.3% (n = 144) would
      recommend the app to their friends and family. Four broad themes relating to how
      the app helped toothbrushing were reported. These themes were motivation,
      education, compliance and perceived benefits. CONCLUSION: A mobile app is a
      promising tool to motivate an evidence-based oral hygiene routine.

PMID- 26315197
TI  - A multivariate statistical analysis on variables affecting inferior alveolar
      nerve damage during third molar surgery.
AB  - AIM: The risk factors associated with inferior alveolar nerve damage during third
      molar surgery were investigated. MATERIAL AND METHODS: Surgeries performed during
      a period of 50 months by a single expert surgeon were reviewed. Only those
      surgeries that met the selected inclusion criteria were considered for this
      study. The following tests were applied for the statistical analysis: the
      Kolmogorov-Smirnov test, the principal components analysis, the Mann-Whitney U
      test, the two-tailed exact Fisher test and the Bonferroni sequential correction.
      RESULTS: The surgical difficulty index, multi-rooted third molars and changes in
      the inferior alveolar nerve running in relation to the tooth roots are predictors
      of nerve damage. CONCLUSIONS: Computed tomography is mandatory when the nerve is
      superimposed on the tooth root on the ortopantomography. SCIENTIFIC RATIONALE FOR
      STUDY: Lower third molar extraction is one of the most common procedures in oral
      and maxillofacial surgery, and it is burdened by the risk of inferior alveolar
      nerve damage. Understanding which factors are able to predict this complication
      is therefore essential in correctly programming surgery. PRINCIPAL FINDINGS:
      Surgical difficulty index, multi-rooted third molars and changes in inferior
      alveolar nerve running in relation to the tooth roots are predictors of nerve
      damage. PRACTICAL IMPLICATIONS: If, on the orthopantomography, the nerve is
      superimposed on the tooth root, a computed tomography is mandatory to define all
      of these variables.

PMID- 26315198
TI  - Linezolid extracorporeal removal during haemodialysis with high cut-off membrane
      in critically ill patients.
AB  - Continuous venovenous haemodialysis with high cut-off membrane (HCO-CVVHD) is
      often used in critically ill septic patients with acute kidney injury (AKI) to
      sustain renal function and to remove circulating inflammatory mediators. The aim
      of this study was to analyse the extracorporeal removal of linezolid and related
      alterations in pharmacokinetic/pharmacodynamic (PK/PD) parameters during HCO
      CVVHD. Three critically ill septic patients with AKI, treated with linezolid and
      HCO-CVVHD, were prospectively observed. To calculate the extracorporeal clearance
      of linezolid and the PK parameters, effluent, pre-filter and post-filter samples
      were contemporaneously collected before linezolid infusion, just after 1-h
      infusion (maximum serum concentration; C(max)), at 3 h and 6 h after dosing, and
      before the next dose (trough serum concentration; C(min)). Linezolid C(max) and
      C(min) (pre-filter) ranged from 10.4-23.5 mg/L and from 2.9-10.3 mg/L. The
      dialysate saturation coefficient was 0.66-0.85 and the extracorporeal clearance
      with a diffusive dose of 35 m L/kg/h ranged from 2.1-2.5 L/h. Total linezolid
      clearance was between 1.7 L/h and 6.3 L/h. The total area under the plasma
      concentration-time curve (AUC0-infinity) ranged from 95.1 mgh/L to 352.9 mgh/L,
      in accordance with the different clinical conditions. AUCfree/MIC ratios were
      always <85 for an MIC of 4.0 mg/L, and two of three patients did not reach the
      optimal PK/PD target of >=85 even when using an MIC of 2.0 mg/L. Although
      extracorporeal clearance may affect linezolid total clearance, the clinical
      features of critically ill septic patients appear to be mainly responsible for
      the high variability of linezolid serum concentrations.

PMID- 26315200
TI  - Review article series on the state of recent evidence in childhood cancer.

PMID- 26315199
TI  - In vitro activity of ceftolozane/tazobactam against clinical isolates of
      Pseudomonas aeruginosa and Enterobacteriaceae recovered in Spanish medical
      centres: Results of the CENIT study.
AB  - Ceftolozane/tazobactam is a novel antimicrobial agent with activity against
      Pseudomonas aeruginosa, including drug-resistant strains, and other Gram-negative
      pathogens, including most extended-spectrum beta-lactamase (ESBL)-producing
      Enterobacteriaceae. The CENIT study evaluated the in vitro activity of
      ceftolozane/tazobactam and comparators against clinical isolates of P. aeruginosa
      (n=500) and Enterobacteriaceae (n=500) collected from patients with complicated
      intra-abdominal, complicated urinary tract, lower respiratory tract or
      bloodstream infections in 10 medical centres in Spain (January-September 2013).
      Antimicrobial susceptibility was determined by the ISO broth microdilution method
      using commercial dry-form panels and results were interpreted per EUCAST and CLSI
      guidelines and for ceftolozane/tazobactam with FDA criteria.
      Ceftolozane/tazobactam and ceftolozane alone were the most potent (MIC(50/90),
      0.5/4 mg/L) agents tested against all P. aeruginosa isolates. This advantage was
      maintained regardless of resistance phenotype, even against isolates resistant to
      multiple antibiotics. Ceftolozane/tazobactam demonstrated excellent overall
      activity (MIC50/90, 0.25/0.5 mg/L) against all 250 Escherichia coli isolates,
      including isolates displaying a wild-type (MIC(90), 0.25/0.25 mg/L) or ESBL
      (MIC(50/90), 0.5/1mg/L) phenotype, and good activity against isolates displaying
      an AmpC-like phenotype (MIC range 0.25-4 mg/L). Ceftolozane/tazobactam
      demonstrated good overall activity (MIC(50/90), 0.25/4 mg/L) against all 104
      Klebsiella spp. isolates, although activity was lower against those with an ESBL
      phenotype (MIC(50/90), 4/16 mg/L), and was inactive against the carbapenemase
      producing isolates (MIC>=64 mg/L). Ceftolozane/tazobactam demonstrated excellent
      in vitro activity against most of the P. aeruginosa and Enterobacteriaceae
      clinical isolates obtained from medical centres in Spain, supporting the
      potential value of ceftolozane/tazobactam in treating infections due to these
      pathogens.

PMID- 26315201
TI  - Erythromelalgia with a linear pattern in a 12-year-old girl.
AB  - Erythromelalgia is a rare clinical syndrome characterized by erythema, increased
      temperature, and severe burning pain that can be aggravated by warmth or relieved
      by cold. Erythromelalgia occurs either as a primary, idiopathic form, or
      secondary to a number of diseases and conditions. Although fairly well studied in
      adults, the characteristics, pathogenesis, and natural history are poorly
      characterized in the pediatric age group. Different therapeutic options have been
      tried, but no optimal treatment has been suggested for erythromelalgia. We report
      a rare case of linear erythromelalgia in a 12-year-old girl involving her central
      body from the peripheral extremities, which seemed to be secondary due to
      vasculitis. Clinical progress waxed and waned on maintenance aspirin and
      propranolol. 

PMID- 26315202
TI  - Renal-limited necrotizing granulomatous vasculitis in a pediatric patient.
AB  - A 10-year-old girl presented with mild proteinuria and hypertension. Laboratory
      data indicated slightly elevated serum creatinine (0.67 mg/dL) and elevated serum
      IgG (2111 mg/dL). On renal arteriography mild stenosis over the entire length of
      the right renal artery and irregular stenosis of the interlobar arteries in the
      right kidney were seen. She was diagnosed with renovascular hypertension, and
      received conventional anti-hypertensive therapy, but did not respond to them. The
      right kidney had atrophy and dysfunction on technetium-99m-labeled
      dimercaptosuccinic acid renal scintigraphy, and was therefore resected.
      Histopathology of the kidney indicated severe necrotizing granulomatous
      vasculitis affecting the arteries from the renal hilus to the interlobar area.
      After nephrectomy plus steroid pulse therapy, blood pressure and urinary protein
      returned to normal. To our knowledge, this is the first report of necrotizing
      granulomatous vasculitis limited to the medium-sized renal arteries.

PMID- 26315203
TI  - Staphylococcus aureus endocarditis and pyomyositis: Rare complications of
      rotavirus gastroenteritis.
AB  - Rotavirus may cause life-threatening complications in untreated patients during
      the course of gastroenteritis. Electrolyte imbalance, bacteremia and sepsis are
      the most common complications of rotavirus gastroenteritis (RG). It is believed
      that translocation of intestinal microorganisms as a result of intestinal
      epithelium dysfunction is the underlying mechanism of bacteremia in RG. Although
      Gram-negative bacteremia has been noted as a complication in RG, Staphylococcus
      aureus bacteremia and endocarditis have not been reported previously. A 22-month
      old boy was admitted with complaints of fever, diarrhea and dehydration. He was
      diagnosed with RG complicated with S. aureus bacteremia, pyomyositis and
      endocarditis. We call attention to these complications in patients with prolonged
      or late-onset fever during RG as rare complications of the disease. 

PMID- 26315204
TI  - Acute acalculous cholecystitis with eosinophilic infiltration.
AB  - We report a case of acute acalculous cholecystitis with eosinophilic
      infiltration. A previously healthy 6-year-old boy was referred with right
      abdominal pain. Imaging demonstrated marked thickening of the gallbladder wall
      and peri-cholecystic effusion. Acute acalculous cholecystitis was diagnosed.
      Symptoms persisted despite conservative treatment, therefore cholecystectomy was
      performed. Pathology indicated infiltration of eosinophils into all layers of the
      gallbladder wall. The postoperative course was uneventful and the patient has had
      no further symptoms. Eosinophilic cholecystitis is acute acalculous cholecystitis
      with infiltration of eosinophils. The causes include parasites, gallstones,
      allergies, and medications. In addition, it may be seen in conjunction with
      eosinophilic gastroenteritis, eosinophilic pancreatitis, or both. An allergic
      reaction to abnormal bile is thought to be the underlying cause. The present case
      did not fulfill the diagnostic criteria of eosinophilic cholecystitis, but this
      may have been in the process of developing. 

PMID- 26315205
TI  - Differing phenotypes of Moyamoya disease in a familial case involving
      heterozygous c.14429G > A variant in RNF213.
AB  - Moyamoya disease (MMD) is a chronic steno-occlusive arteriopathy involving the
      development of abnormal collateral vessels. Ring finger protein (RNF213) on the
      17q25.3 locus was identified as an MMD-susceptibility gene in East Asian
      populations. We report a 5-year-old Japanese boy diagnosed with cerebral
      infarction and unilateral MMD. Magnetic resonance angiography (MRA) showed severe
      stenosis of the left internal carotid artery (ICA), terminal portion of the left
      ICA, and left origin of the posterior cerebral artery. Genetic testing indicated
      a heterozygous c.14429G > A (formerly described as c.14576G > A) variant in
      RNF213. The boy's mother had no neurological symptoms, but sequencing of RNF213
      showed the same variant, and MRA indicated stenosis of the terminal bilateral
      ICA. This is the first report, to our knowledge, of different MMD phenotypes in a
      familial case involving the same heterozygous c.14429G > A variant in RNF213.
      Genetic testing for RNF213 is suggested for family member screening.

PMID- 26315206
TI  - Systemic multi-organ involvement in chronic active Epstein-Barr virus disease.

PMID- 26315207
TI  - Cartilage matrix infection in young children by Kingella kingae.

PMID- 26315208
TI  - [Clinical and paraclinical prognostic factors in non-small cell lung cancer
      surgery].
AB  - INTRODUCTION: Lung cancer prognosis is mainly based on the TNM, histology and
      molecular biology. Our aim was to analyze the prognostic value of certain
      clinical and paraclinical variables. PATIENTS AND METHODS: We studied among 6105
      patients operated on, divided during 3 time-periods (1979 to 2010), the following
      prognostic factors: type of surgery, pTNM, histology, age, sex, smoking history,
      clinical presentation, and paraclinical variables. RESULTS: Postoperative
      mortality was 4% (243/6105), rate of complications was 23.3% (1424/6105). The 5
      year overall survival was 43.2% and 10-year was 27%. Best survival was observed
      after complete resection (R0) (P<10(-6)), lobectomy (P<10(-6)), lymph node
      dissection (P=0.0006), early pTNM stages (P<10(-6)), absence of a solid component
      in adenocarcinoma. Other pejorative factors were: male gender (P=10(-5)), age
      (P=0.0000002), comorbidity (P=0.016), history of cancer (P<10(-5)), postoperative
      complications (P=0.0018), FEV lower than 80% (P=0.0000025), time-periods (P<10(
      6)). All these factors were confirmed by multivariate analysis, except gender.
      Smoking was not poor prognostic factor in univariate analysis (P=0.09) but became
      significant in the multivariate one (P=0.013). CONCLUSION: Medical and human
      factors, and the general physiological state, play an important role in prognosis
      after surgery. We do not know their exact meaning and, like studies on
      chemotherapy, they justify special research.

PMID- 26315210
TI  - A review of guidance on immunization in persons with defective or deficient
      splenic function.
AB  - The spleen acts as a blood filter and lymphopoietic organ. Asplenic and
      hyposplenic individuals are more susceptible to serious infections caused by
      encapsulated bacteria but they can be protected by antibiotic prophylaxis and
      immunizations. Recent progress in vaccinology means prophylaxis is now successful
      in the vast majority of serious infections with pneumococci, meningococci and
      Haemophilus influenzae type b responsible for the majority of cases of
      overwhelming sepsis in asplenic patients. Current guidelines are coherent.
      Physicians treating patients with conditions associated with hyposplenism are
      ethically obliged to immunize their patients using the vaccines currently
      available to protect them from largely preventable, life-threatening infections. 

PMID- 26315209
TI  - CSN and CAVA: variant annotation tools for rapid, robust next-generation
      sequencing analysis in the clinical setting.
AB  - BACKGROUND: Next-generation sequencing (NGS) offers unprecedented opportunities
      to expand clinical genomics. It also presents challenges with respect to
      integration with data from other sequencing methods and historical data.
      Provision of consistent, clinically applicable variant annotation of NGS data has
      proved difficult, particularly of indels, an important variant class in clinical
      genomics. Annotation in relation to a reference genome sequence, the DNA strand
      of coding transcripts and potential alternative variant representations has not
      been well addressed. Here we present tools that address these challenges to
      provide rapid, standardized, clinically appropriate annotation of NGS data in
      line with existing clinical standards. METHODS: We developed a clinical
      sequencing nomenclature (CSN), a fixed variant annotation consistent with the
      principles of the Human Genome Variation Society (HGVS) guidelines, optimized for
      automated variant annotation of NGS data. To deliver high-throughput CSN
      annotation we created CAVA (Clinical Annotation of VAriants), a fast, lightweight
      tool designed for easy incorporation into NGS pipelines. CAVA allows transcript
      specification, appropriately accommodates the strand of a gene transcript and
      flags variants with alternative annotations to facilitate clinical interpretation
      and comparison with other datasets. We evaluated CAVA in exome data and a
      clinical BRCA1/BRCA2 gene testing pipeline. RESULTS: CAVA generated CSN calls for
      10,313,034 variants in the ExAC database in 13.44 hours, and annotated the
      ICR1000 exome series in 6.5 hours. Evaluation of 731 different indels from a
      single individual revealed 92 % had alternative representations in left aligned
      and right aligned data. Annotation of left aligned data, as performed by many
      annotation tools, would thus give clinically discrepant annotation for the 339
      (46 %) indels in genes transcribed from the forward DNA strand. By contrast, CAVA
      provides the correct clinical annotation for all indels. CAVA also flagged the
      370 indels with alternative representations of a different functional class,
      which may profoundly influence clinical interpretation. CAVA annotation of 50
      BRCA1/BRCA2 gene mutations from a clinical pipeline gave 100 % concordance with
      Sanger data; only 8/25 BRCA2 mutations were correctly clinically annotated by
      other tools. CONCLUSIONS: CAVA is a freely available tool that provides rapid,
      robust, high-throughput clinical annotation of NGS data, using a standardized
      clinical sequencing nomenclature.

PMID- 26315211
TI  - Faculty Development for a New Curriculum: Implementing a Strategy for Veterinary
      Teachers within the Wider University Context.
AB  - Faculty development in veterinary education is receiving increasing attention
      internationally and is considered of particular importance during periods of
      organizational or curricular change. This report outlines a faculty development
      strategy developed since October 2012 at the University of Bristol Veterinary
      School, in parallel with the development and implementation of a new curriculum.
      The aim of the strategy is to deliver accessible, contextual faculty development
      workshops for clinical and non-clinical staff involved in veterinary student
      training, thereby equipping staff with the skills and support to deliver high
      quality teaching in a modern curriculum. In October 2014, these workshops became
      embedded within the new University of Bristol Continuing Professional Development
      scheme, Cultivating Research and Teaching Excellence. This scheme ensures that
      staff have a clear and structured route to achieving formal recognition of their
      teaching practice as well as access to a wide range of resources to further their
      overall professional development. The key challenges and constraints are
      discussed. 

PMID- 26315212
TI  - Veterinarian-Client Communication Skills: Current State, Relevance, and
      Opportunities for Improvement.
AB  - Communication is increasingly recognized as a core skill for veterinary
      practitioners, and in recent years, attention to communication competency and
      skills training has increased. To gain an up-to-date assessment of the current
      state of veterinary communication skills and training, we conducted a survey
      among veterinary practitioners in the United Kingdom and United States in
      2012/2013. The questionnaire was used to assess the current state, relevance, and
      adequacy of veterinary communication skills among veterinary practitioners, to
      assess interest in further training, and to understand perceived challenges in
      communicating with clients. There was an overall response rate of 29.6% (1,774 of
      6,000 recipients), with a higher response rate for UK-based practitioners (39.7%)
      than practitioners in the US (19.5%). Ninety-eight percent of respondents agreed
      that communication skills were as important as or more important than clinical
      knowledge. Forty-one percent of respondents had received formal veterinary
      communication skills training during veterinary school, and 47% had received
      training post-graduation. Thirty-five percent said their veterinary communication
      skills training during veterinary school prepared them well or very well for
      communicating with clients about the health of their pets, compared to 61% of
      those receiving post-graduate training. Forty percent said they would be
      interested in further veterinary communication skills training, with the
      preferred methods being simulated consultations and online training. While there
      has been increased emphasis on communication skills training during and after
      veterinary school, there is a need for more relevant and accessible training. 

PMID- 26315213
TI  - Do Veterinary Students See a Need for More In-Course Discussion? A Survey.
AB  - Rather than merely transferring information, veterinary education should
      stimulate and motivate students and encourage them to think. Currently in
      veterinary education, most curricula use the method of frontal teaching (e.g., in
      lectures). A student-centered critical approach to information is rarely used.
      Our research sought to determine if students consider in-course discussion useful
      and if sufficient possibilities for discussion are provided and supported by
      their lecturers. In December 2013, we conducted a survey of fourth-year students.
      Specifically, we wanted to know if students consider in-course discussion about
      course content useful for successful learning and if students wish to have more
      opportunities for discussion during class time. Finally, we wanted to identify
      barriers that limit the students' motivation and ability to engage in discussion
      of course content. In total, 105 students completed the survey. The majority of
      students agreed or strongly agreed that clinical topics should be discussed
      during class time. Frequently stated reasons were improved learning (85.7%) and
      the opportunity to look at topics from different perspectives (92.4%). In
      conclusion, we found a considerable dearth of and request for discussion within
      veterinary education. In light of these findings, we emphasize the need for new
      teaching strategies that promote independent thinking and critical questioning.
      We suggest the implementation of more discussion opportunities in well considered
      and moderated settings in veterinary teaching. 

PMID- 26315214
TI  - Does a Rater's Professional Background Influence Communication Skills Assessment?
AB  - There is increasing pressure in veterinary education to teach and assess
      communication skills, with the Objective Structured Clinical Examination (OSCE)
      being the most common assessment method. Previous research reveals that raters
      are a large source of variance in OSCEs. This study focused on examining the
      effect of raters' professional background as a source of variance when assessing
      students' communication skills. Twenty-three raters were categorized according to
      their professional background: clinical sciences (n=11), basic sciences (n=4),
      clinical communication (n=5), or hospital administrator/clinical skills
      technicians (n=3). Raters from each professional background were assigned to the
      same station and assessed the same students during two four-station OSCEs.
      Students were in year 2 of their pre-clinical program. Repeated-measures ANOVA
      results showed that OSCE scores awarded by the rater groups differed
      significantly: (F(matched_station_1) [2,91]=6.97, p=.002), (F(matched_station_2)
      [3,90]=13.95, p=.001), (F(matched_station_3) [3,90]=8.76, p=.001), and
      ((Fmatched_station_4) [2,91]=30.60, p=.001). A significant time effect between
      the two OSCEs was calculated for matched stations 1, 2, and 4, indicating
      improved student performances. Raters with a clinical communication skills
      background assigned scores that were significantly lower compared to the other
      rater groups. Analysis of written feedback provided by the clinical sciences
      raters showed that they were influenced by the students' clinical knowledge of
      the case and that they did not rely solely on the communication checklist items.
      This study shows that it is important to consider rater background both in
      recruitment and training programs for communication skills' assessment.

PMID- 26315215
TI  - Developing Confidence in Uncertainty: Conflicting Roles of Trainees as They
      Become Educators in Veterinary and Human Medicine.
AB  - The important role of medical trainees (interns and residents) as teachers is
      increasingly recognized in veterinary and human medicine, but often is not
      supported through adult learning programs or other preparatory training methods.
      To develop appropriate teaching programs focused on effective clinical teaching,
      more understanding is needed about the support required for the trainee's
      teaching role. Following discussion among faculty members from education and
      veterinary and pediatric medicine, an experienced external observer and expert in
      higher education observed 28 incoming and outgoing veterinary and pediatric
      trainees in multiple clinical teaching settings over 10 weeks. Using an
      interpretative approach to analyze the data, we identified five dynamics that
      could serve as the foundation for a new program to support clinical teaching: (1)
      Novice-Expert, recognizing transitions between roles; (2) Collaboration
      Individuality, recognizing the power of peer learning; (3) Confidence
      Uncertainty, regarding the confidence to act; (4) Role-Interdisciplinarity,
      recognizing the ability to maintain a discrete role and yet synthesize knowledge
      and cope with complexity; and (5) Socialization-Identity, taking on different
      selves. Trainees in veterinary and human medicine appeared to have similar needs
      for support in teaching and would benefit from a variety of strategies: faculty
      should provide written guidelines and practical teaching tips; set clear
      expectations; establish sustained support strategies, including contact with an
      impartial educator; identify physical spaces in which to discuss teaching;
      provide continuous feedback; and facilitate peer observation across medical and
      veterinary clinical environments. 

PMID- 26315216
TI  - Nanomaterial-enabled Rapid Detection of Water Contaminants.
AB  - Water contaminants, e.g., inorganic chemicals and microorganisms, are critical
      metrics for water quality monitoring and have significant impacts on human health
      and plants/organisms living in water. The scope and focus of this review is
      nanomaterial-based optical, electronic, and electrochemical sensors for rapid
      detection of water contaminants, e.g., heavy metals, anions, and bacteria. These
      contaminants are commonly found in different water systems. The importance of
      water quality monitoring and control demands significant advancement in the
      detection of contaminants in water because current sensing technologies for water
      contaminants have limitations. The advantages of nanomaterial-based sensing
      technologies are highlighted and recent progress on nanomaterial-based sensors
      for rapid water contaminant detection is discussed. An outlook for future
      research into this rapidly growing field is also provided. 

PMID- 26315217
TI  - Probiotic Bifidobacterium longum alters gut luminal metabolism through
      modification of the gut microbial community.
AB  - Probiotics are well known as health-promoting agents that modulate intestinal
      microbiota. However, the molecular mechanisms underlying this effect remain
      unclear. Using gnotobiotic mice harboring 15 strains of predominant human gut
      derived microbiota (HGM), we investigated the effects of Bifidobacterium longum
      BB536 (BB536-HGM) supplementation on the gut luminal metabolism. Nuclear magnetic
      resonance (NMR)-based metabolomics showed significantly increased fecal levels of
      pimelate, a precursor of biotin, and butyrate in the BB536-HGM group. In
      addition, the bioassay revealed significantly elevated fecal levels of biotin in
      the BB536-HGM group. Metatranscriptomic analysis of fecal microbiota followed by
      an in vitro bioassay indicated that the elevated biotin level was due to an
      alteration in metabolism related to biotin synthesis by Bacteroides caccae in
      this mouse model. Furthermore, the proportion of Eubacterium rectale, a butyrate
      producer, was significantly higher in the BB536-HGM group than in the group
      without B. longum BB536 supplementation. Our findings help to elucidate the
      molecular basis underlying the effect of B. longum BB536 on the gut luminal
      metabolism through its interactions with the microbial community. 

PMID- 26315218
TI  - My year as journal editor.

PMID- 26315219
TI  - [Physician heroes--and antiheroes].

PMID- 26315220
TI  - [Re: Different guidelines for treatment of prostate cancer].

PMID- 26315223
TI  - [Re: Medicinal cannabis].

PMID- 26315224
TI  - [Re: E-cigarettes--harmful or beneficial?].

PMID- 26315225
TI  - [T. Sanner & T.K. Grimsrud reply].

PMID- 26315226
TI  - [Re: How doctors do not wish to die].

PMID- 26315227
TI  - [Re: Meeting yourself and others in the door].

PMID- 26315230
TI  - [Treatment for stage I-testicular cancer should be assessed individually].

PMID- 26315231
TI  - [All suicides are not due to treatment failure].

PMID- 26315232
TI  - [Less sitting--better health?].

PMID- 26315233
TI  - [Does Alzheimer Disease mean dementia?].

PMID- 26315236
TI  - Is childhood stress associated with shorter telomeres?
AB  - BACKGROUND: It has been shown that severe stress in childhood is harmful to later
      health. New research aims to ascertain whether - and if so, how - the telomeres,
      the protective caps at the end of our chromosomes, may be one of the links
      between this type of experience and later morbidity. Here we present an overview
      of studies which have examined the association between stress in childhood and
      length of telomeres. METHOD: The review encompasses 26 original studies found
      through a literature search in PubMed. We included studies of the relationship
      between length of telomeres and various stress-inducing factors from conception
      throughout childhood and adolescence. RESULTS: The studies were grouped into four
      topics. The empirical research base for mother's stress in pregnancy and parents'
      ability to care for their children is too small to draw any conclusions.
      Psychosocial stress in childhood was associated with shorter telomere length in
      12 of 14 studies. Socioeconomic status in childhood was not unequivocally
      associated with telomere length. INTERPRETATION: Shorter telomeres are possibly
      associated with psychosocial stress in childhood. This field of research is still
      new, and more longitudinal studies are needed with an emphasis on childhood
      experiences and coordination of measurement variables and results measurement in
      order to confirm this association.

PMID- 26315237
TI  - Cluster headache.

PMID- 26315238
TI  - Pale pink blood vessels in the back of the eye.

PMID- 26315239
TI  - [A woman in her 70s with decompensated heart failure during surgery].

PMID- 26315240
TI  - A man in his 50s with high ferritin levels and increasing cognitive impairment.

PMID- 26315241
TI  - Priority-setting criteria in the Norwegian health services.

PMID- 26315242
TI  - Age and severity.

PMID- 26315243
TI  - [How big should an intensive care unit be?].

PMID- 26315244
TI  - [Body or head transplantation?].

PMID- 26315255
TI  - The incidence and sites of Nasopharyngeal carcinoma (NPC) metastases on FDG
      PET/CT scans.
AB  - INTRODUCTION: The only investigation to determine if a whole body FDG PET/CT scan
      is helpful in the evaluation of NPC is a study from Stanford. In this study, 26
      patients with whole body PET/CT, were evaluated for lesions below adrenals and
      showed that 7.7% of distant metastases were below adrenals. Our study comparing
      distant metastases below diaphragm with Stanford study to evaluate the need for
      whole body PET/CT. MATERIAL AND METHODS: Reports of NPC patients in Singapore
      General Hospital were reviewed. The lesions were analyzed for total number and
      number below diaphragm. The lesions below the diaphragm were further analyzed if
      they were solitary or involved multiple areas and if any additional lesions were
      above diaphragm. RESULTS: 717 reports were included in final analysis. The number
      of FDG avid lesions in these reports was 709. Distant metastases represented 352
      of the 709 lesions. The number of lesions below diaphragm was 152, of the lesions
      below diaphragm only 16 of lesions have no co-existing distant metastases above
      diaphragm. From these lesions, there were only 12 solitary lesions. The other 4
      has concurrent metastases but all localized below diaphragm. CONCLUSION: Compared
      to Stanford study, number of reports is more representative in this study and the
      yield is much lower (7.7% versus 2.26%). From the results of our study we can
      consider limiting the scan area from vertex to below diaphragm. However, the
      symptoms and clinical presentation of the patient will further direct the
      requesting physician in the area to be imaged.

PMID- 26315256
TI  - Chronic stress promotes oral cancer growth and angiogenesis with increased
      circulating catecholamine and glucocorticoid levels in a mouse model.
AB  - OBJECTIVES: Chronic stress was previously reported to play a role in the
      development of oral cancer, yet the correlation between stressors and oral cancer
      progression is not well understood. MATERIALS AND METHODS: We implanted human
      oral cancer cell line CAL 27 in nude mice to investigate the effects of chronic
      stress on tumor growth, and designed a physical restraint system to create an
      experimentally stressed animal model, in which periodic immobilization induced
      characteristic chronic stress. Tumor burdened animal were randomly assigned into
      four groups: (a) control group, (b) daily stress for 2h with light, (c) daily
      stress for 2h in dark, and (d) daily stress for 6h with light. Animals were
      sacrificed after three weeks. Various analyses were performed on parameters
      including body weight, tumor weight, in situ expression of MMP-2 and VEGF, and
      the plasma concentrations of epinephrine, norepinephrine and glucocorticoid.
      RESULTS AND CONCLUSION: Our data showed that chronic stress resulted in greater
      tumor size, more expression of MMP-2 and VEGF, higher level of plasma
      catecholamines, and more invasive growth of oral carcinoma cells in a mice model.
      We have successfully set up an animal model, which studied the effect of chronic
      stress on oral carcinoma growth rate and progression. These data further
      suggested that catecholamine and glucocorticoid might stimulate tumor progression
      under chronic stress.

PMID- 26315257
TI  - Endometriosis in teenagers.
AB  - Endometriosis affects a significant proportion of teenagers. Published studies
      suggest that laparoscopically confirmed endometriosis could be found in over 60%
      of adolescent girls undergoing laparoscopic investigation for pain, in 75% of
      girls with chronic pelvic pain resistant to treatment and in 70% of girls with
      dysmenorrhea and in approximately 50% of girls with chronic pelvic pain not
      necessarily resistant to treatment. Both early and advanced forms, including deep
      endometriosis have been reported to be present in teenagers. It has recently been
      claimed that deep endometriosis has its roots in teenage years. Risk factors
      include obstructive mullerian anomalies, family history, early menarche and early
      onset dysmenorrhea. Both surgical and medical treatment approaches are used for
      treatment in this age group, but care should be taken when treatment with GnRHa
      and progestins is being considered due to their potential impact on bone
      formation. Further studies are urgently needed to determine whether early
      diagnosis and treatment of teenage endometriosis lead to better long term
      outcomes or simply increase number of interventions without preventing
      progression of the disease. 

PMID- 26315258
TI  - Hematologic neoplasms: interpreting lung findings in chest computed tomography.
AB  - Lung disease is very common in patients with hematologic neoplasms and varies in
      function of the underlying disease and its treatment. Lung involvement is
      associated with high morbidity and mortality, so it requires early appropriate
      treatment. Chest computed tomography (CT) and the analysis of biologic specimens
      are the first line diagnostic tools in these patients, and sometimes invasive
      methods are necessary. Interpreting the images requires an analysis of the
      clinical context, which is often complex. Starting from the knowledge about the
      differential diagnosis of lung findings that radiologists acquire during
      training, this article aims to explain the key clinical and radiological aspects
      that make it possible to orient the diagnosis correctly and to understand the
      current role of CT in the treatment strategy for this group of patients. 

PMID- 26315259
TI  - Parametric methods for characterizing myocardial tissue by magnetic resonance
      imaging (part 2): T2 mapping.
AB  - Cardiac magnetic resonance imaging is considered the reference technique for
      characterizing myocardial tissue; for example, T2-weighted sequences make it
      possible to evaluate areas of edema or myocardial inflammation. However,
      traditional sequences have many limitations and provide only qualitative
      information. Moreover, traditional sequences depend on the reference to remote
      myocardium or skeletal muscle, which limits their ability to detect and quantify
      diffuse myocardial damage. Recently developed magnetic resonance myocardial
      mapping techniques enable quantitative assessment of parameters indicative of
      edema. These techniques have proven better than traditional sequences both in
      acute cardiomyopathy and in acute ischemic heart disease. This article
      synthesizes current developments in T2 mapping as well as their clinical
      applications and limitations. 

PMID- 26315260
TI  - The phase diagram of high-pressure superionic ice.
AB  - Superionic ice is a special group of ice phases at high temperature and pressure,
      which may exist in ice-rich planets and exoplanets. In superionic ice liquid
      hydrogen coexists with a crystalline oxygen sublattice. At high pressures, the
      properties of superionic ice are largely unknown. Here we report evidence that
      from 280 GPa to 1.3 TPa, there are several competing phases within the close
      packed oxygen sublattice. At even higher pressure, the close-packed structure of
      the oxygen sublattice becomes unstable to a new unusual superionic phase in which
      the oxygen sublattice takes the P2(1)/c symmetry. We also discover that higher
      pressure phases have lower transition temperatures. The diffusive hydrogen in the
      P2(1)/c superionic phase shows strong anisotropic behaviour and forms a quasi-two
      dimensional liquid. The ionic conductivity changes abruptly in the solid to close
      packed superionic phase transition, but continuously in the solid to P2(1)/c
      superionic phase transition.

PMID- 26315261
TI  - Assessing the damage control resuscitation: development, drivers and direction.
AB  - Damage control resuscitation (DCR) has become a more widely adopted acute
      management strategy over the past decade. A cornerstone of this strategy is the
      performance of an initial limited surgical intervention for the control of active
      bleeding and contamination. This technique is indicated where significant
      physiological compromise exists and immediate surgical intervention is required.
      This damage control surgery itself is completed judiciously to allow a period of
      resuscitative stabilisation before later definitive surgical solutions. This
      discussion describes the three further principles of DCR and then explores the
      rationale and drivers behind the development of this approach. 

PMID- 26315262
TI  - The role of endobronchial ultrasound-guided fine needle aspiration in the
      diagnosis of pleural mesothelioma.
AB  - OBJECTIVE: The aims of the present study were to investigate the role of
      endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in
      the diagnosis of malignant pleural mesothelioma (MPM), and to identify specific
      clinical settings in which this procedure can be recommended. METHODS: We
      retrospectively reviewed the clinical and pathological files of patients having
      undergone EBUS-TBNA from February 2011 to October 2014 to investigate thoracic
      lesions. Among 736 patients, we identified four of them with a diagnosis of MPM
      achieved primarily through EBUS-TBNA. The diagnosis was made on formalin-fixed
      paraffin-embedded cell blocks, by checking the expression of mesothelial and
      carcinomatous-specific markers. RESULTS: In all patients, the collected tissue
      was adequate, and the histological analysis in association with
      immunohistochemistry led us to the diagnosis of malignant pleural mesothelioma.
      In three patients, the diagnosis of mesothelioma was clinically suspected, as
      patients presented with diffuse pleural thickening. In two patients,
      videothoracoscopy was not possible owing to the 'dry' presentation of the pleural
      disease and the site of thickening. In this setting, EBUS-TBNA was considered, at
      a multidisciplinary consensus meeting, as the most adequate available method to
      obtain a histological diagnosis. CONCLUSION: EBUS-TBNA may be a valuable
      diagnostic technique in the field of pleural pathology in selected clinical
      settings. More specifically 'dry' mesothelioma forming para-tracheal nodules or
      masses not accessible by surgery or by computed tomography/ultrasonogaphy-guided
      needle biopsy constitutes a good indication to perform EBUS-TBNA.

PMID- 26315263
TI  - Development of a D genome specific marker resource for diploid and hexaploid
      wheat.
AB  - BACKGROUND: Mapping and map-based cloning of genes that control agriculturally
      and economically important traits remain great challenges for plants with complex
      highly repetitive genomes such as those within the grass tribe, Triticeae.
      Mapping limitations in the Triticeae are primarily due to low frequencies of
      polymorphic gene markers and poor genetic recombination in certain genetic
      regions. Although the abundance of repetitive sequence may pose common problems
      in genome analysis and sequence assembly of large and complex genomes, they
      provide repeat junction markers with random and unbiased distribution throughout
      chromosomes. Hence, development of a high-throughput mapping technology that
      combine both gene-based and repeat junction-based markers is needed to generate
      maps that have better coverage of the entire genome. RESULTS: In this study, the
      available genomics resource of the diploid Aegilop tauschii, the D genome donor
      of bread wheat, were used to develop genome specific markers that can be applied
      for mapping in modern hexaploid wheat. A NimbleGen array containing both gene
      based and repeat junction probe sequences derived from Ae. tauschii was developed
      and used to map the Chinese Spring nullisomic-tetrasomic lines and deletion bin
      lines of the D genome chromosomes. Based on these mapping data, we have now
      anchored 5,171 repeat junction probes and 10,892 gene probes, corresponding to
      5,070 gene markers, to the delineated deletion bins of the D genome. The order of
      the gene-based markers within the deletion bins of the Chinese Spring can be
      inferred based on their positions on the Ae. tauschii genetic map. Analysis of
      the probe sequences against the Chinese Spring chromosome sequence assembly
      database facilitated mapping of the NimbleGen probes to the sequence contigs and
      allowed assignment or ordering of these sequence contigs within the deletion
      bins. The accumulated length of anchored sequence contigs is about 155 Mb,
      representing ~ 3.2 % of the D genome. A specific database was developed to allow
      user to search or BLAST against the probe sequence information and to directly
      download PCR primers for mapping specific genetic loci. CONCLUSIONS: In bread
      wheat, aneuploid stocks have been extensively used to assign markers linked with
      genes/traits to chromosomes, chromosome arms, and their specific bins. Through
      this study, we added thousands of markers to the existing wheat chromosome bin
      map, representing a significant step forward in providing a resource to navigate
      the wheat genome. The database website ( http://probes.pw.usda.gov/ATRJM/ )
      provides easy access and efficient utilization of the data. The resources
      developed herein can aid map-based cloning of traits of interest and the
      sequencing of the D genome of hexaploid wheat.

PMID- 26315264
TI  - Synthesis and X-ray crystal structure of the dirhenium complex Re2(i-C3H7COO)4Cl2
      and its interactions with the DNA purine nucleobases.
AB  - The dirhenium complex Re2(i-C3H7COO)4Cl2 was synthesized and characterized by X
      ray crystallography, (1)H NMR and electronic spectroscopies, and electrospray
      ionization-mass spectrometry. The reactions of Re2(i-C3H7COO)4Cl2 with the
      substituted DNA purine nucleobases guanine (9-methylguanine and 9-ethylguanine)
      and adenine (9-methyladenine and 9-ethyladenine) were investigated by proton
      nuclear magnetic resonance and electronic spectroscopies as well as electrospray
      ionization-mass spectrometry. The data corroborate binding of two 9-methylguanine
      (or 9-ethylguanine) and 9-methyladenine (or 9-ethyladenine) bases per dirhenium
      unit in a bidentate fashion, in equatorial positions, via sites N7/O6 and N1/N6,
      respectively, with concomitant substitution of two carboxylate groups to form a
      single isomer of cis-Re2(i-C3H7COO)2(nucleobase)2Cl2. The binding of the bases to
      the dirhenium core disrupts important nucleobase interactions and may have
      important biological implications with respect to the anticancer activity of
      dirhenium complexes. 

PMID- 26315265
TI  - Shared and unique mutational gene co-occurrences in cancers.
AB  - Cancers are often associated with mutations in multiple genes; thus, studying the
      distributions of genes that harbor cancer-promoting mutations in cancer samples
      and their co-occurrences could provide insights into cancer diagnostics and
      treatment. Using data from the Catalogue of Somatic Mutations in Cancer (COSMIC),
      we found that mutated genes in cancer samples followed a power-law distribution.
      For instance, a few genes were mutated in a large number of samples (designated
      as high-frequent genes), while a large number of genes were only mutated in a few
      samples. This power-law distribution can be found in samples of all cancer types
      as well as individual cancers. In samples where two or more mutated genes are
      found, the high-frequent genes, i.e., those that were frequently mutated, often
      did not co-occur with other genes, while the other genes often tended to co
      occur. Co-occurrences of mutated genes were often unique to a certain cancer;
      however, some co-occurrences were shared by multiple cancer types. Our results
      revealed distinct patterns of high-frequent genes and those that were less
      frequently mutated in the cancer samples in co-occurring and anti-co-occurring
      networks. Our results indicated that distinct treatment strategies should be
      adopted for cancer patients with known high-frequent gene mutations and those
      without. The latter might be better treated with a combination of drugs targeting
      multiple genes. Our results also suggested that possible cross-cancer treatments,
      i.e., the use of the same drug combinations, may treat cancers of different
      histological origins. 

PMID- 26315266
TI  - Natural liposomes and synthetic polymeric structures for biomedical applications.
AB  - In the last decades, the development and design of drug delivery systems have
      attracted great attention. Especially siRNA carriers have been of special
      interest since discovered as suitable tool for gene silencing. Self-assembled
      structures consisting of amphiphilic molecules are the most investigated carriers
      with regards to siRNA delivery. Liposomes as drug vehicles already found their
      way into clinical use, as they are highly biocompatible and their colloidal
      stability and circulation time in blood can be significantly enhanced by
      PEGylation. Fully synthetic polymersomes inspired by these natural structures
      provide enhanced stability and offer a wide range of modification-possibilities.
      Therefore, their design as carrier vehicles has become of great interest. This
      mini-review highlights the possibilities of using polymeric vesicles for
      potential drug delivery and gives a brief overview of their potential regarding
      fine-tuning towards targeted delivery or triggered drug release. 

PMID- 26315267
TI  - 2-Deoxyglucose induces the expression of thioredoxin interacting protein (TXNIP)
      by increasing O-GlcNAcylation - Implications for targeting the Warburg effect in
      cancer cells.
AB  - The high proliferation rate of cancer cells and the microenvironment in the tumor
      tissue require the reprogramming of tumor cell metabolism. The major mechanism of
      metabolic reprogramming in cancer cells is the Warburg effect, defined as the
      preferential utilization of glucose via glycolysis even in the presence of
      oxygen. Targeting the Warburg effect is considered as a promising therapeutic
      strategy in cancer therapy. In this regard, the glycolytic inhibitor 2
      deoxyglucose (2DG) has been evaluated clinically. 2DG exerts its effect by
      directly inhibiting glycolysis at the level of hexokinase and
      phosphoglucoisomerase. In addition, 2DG is also known to induce the expression of
      thioredoxin interacting protein (TXNIP), a tumor suppressor protein and an
      important negative regulator of cellular glucose uptake. Hence, characterization
      of the mechanism through which 2DG regulates TXNIP expression may reveal novel
      approaches to target the Warburg effect in cancer cells. Therefore, in this study
      we sought to test various hypotheses for the mechanistic basis of the 2DG
      dependent TXNIP regulation. We have shown that 2DG induced TXNIP expression is
      independent of carbohydrate response element mediated transcription. Furthermore,
      the induction of TXNIP is neither dependent on the ability of 2DG to deplete
      cellular ATP nor to cause endoplasmic reticulum stress. We found that the 2DG
      induced TXNIP expression is at least in part dependent on the inhibition of the O
      GlcNAcase enzyme and the accumulation of O-GlcNAc modified proteins. These
      results have implications for the identification of therapeutic targets to
      increase TXNIP expression in cancer. 

PMID- 26315268
TI  - Adenylyl cyclase localization to the uropod of aggregating Dictyostelium cells
      requires RacC.
AB  - The localization of adenylyl cyclase A (ACA) to uropod of cells is required for
      the stream formation during Dictyostelium development. RacC is a Dictyostelium
      orthologue of Cdc42. We identified a streaming defect of racC(-) cells as they
      are clearly less polarized and form smaller and fragmented streams. ACA-YFP is
      mainly associated with intracellular vesicular structures, but not with the
      plasma membrane in racC(-) cells. racC(-) cells have a slightly higher number of
      vesicles than Ax3 cells, suggesting that the defect of ACA trafficking is not
      simply due to the lack of vesicle formation. While the ACA-YFP vesicles traveled
      with an average velocity of 9.1 MUm/min in Ax3 cells, a slow and diffusional
      movement without direction with an average velocity of 4 MUm/min was maintained
      in racC(-) cells. Images acquired by using total internal reflection fluorescence
      (TIRF) microscopy and fluorescence recovery after photobleaching (FRAP) analysis
      revealed that a significantly decreased number of ACA-YFP vesicles appeared near
      the cell membrane, indicating a defect in ACA-YFP vesicle trafficking. These
      results suggest an important role of RacC in the rapid and directional movements
      of ACA vesicles on microtubules to the plasma membrane, especially to the back of
      polarized cell.

PMID- 26315269
TI  - Crystal structure of Legionella pneumophila type IV secretion system effector
      LegAS4.
AB  - The SET domain of LegAS4, a type IV secretion system effector of Legionella
      pneumophila, is a eukaryotic protein motif involved in histone methylation and
      epigenetic modulation. The SET domain of LegAS4 is involved in the modification
      of Lys4 of histone H3 (H3K4) in the nucleolus of the host cell, thereby enhancing
      heterochromatic rDNA transcription. Moreover, LegAS4 contains an ankyrin repeat
      domain of unknown function at its C-terminal region. Here, we report the crystal
      structure of LegAS4 in complex with S-adenosyl-l-methionine (SAM). Our data
      indicate that the ankyrin repeats interact extensively with the SET domain,
      especially with the SAM-binding amino acids, through conserved residues.
      Conserved surface analysis marks Glu159, Glu203, and Glu206 on the SET domain
      serve as candidate residues involved in interaction with the positively charged
      histone tail. Conserved surface residues on the ankyrin repeat domain surround a
      small pocket, which is suspected to serve as a binding site for an unknown
      ligand.

PMID- 26315270
TI  - GLP-1 contributes to increases in PGC-1alpha expression by downregulating miR-23a
      to reduce apoptosis.
AB  - GLP-1 can help to overcome problems of liver cells metabolism, not only
      pancreatic cell. But the explicit mechanism of this effect remains unclear. In
      recent years, microRNAs have received the attention of researchers and some
      microRNAs have important implications for diabetes. The mitochondrial protective
      gene PGC-1alpha is also closely related to diabetes, and UCP2 is related to anti
      mitochondrial oxidative stress, but the mechanism of action of these genes is
      unclear. In this study, we used HepG2 cell line and used the cell counting kit
      (CCK) to measure the cell viability with GLP-1(7-36) and/or glucotoxicity. To
      investigate alterations in gene expression resulting from incubation with GLP-1
      (7-36) or hyperglycaemia, the RNA expression levels of miR-23a, PGC-1alpha, Bak,
      Bax and UCP2 were quantified using real-time PCR. The protein levels of PGC
      1alpha were determined by western blot. The role of miR-23a in the regulation of
      PGC-1alpha was further assessed through cell transfection to downregulate of miR
      23a expression. In this study, the viability of HepG2 hepatocytes was decreased
      under hyperglycaemia, but incubation with 10 nmol/L GLP-1 (7-36) amide for 24 h
      significantly increased the viability and decreased the mRNA expression levels of
      Bax and Bak. Incubation with GLP-1(7-36) amide for 24 h attenuated the RNA
      expression of miR-23a and increased the mRNA and protein expression of PGC
      1alpha. Inhibition of miR-23a expression by cell transfection led to increases in
      the mRNA and protein expression of PGC-1alpha. In addition, the mRNA expression
      of UCP2 increased after incubation with GLP-1(7-36) for 24 h. In conclusion, GLP
      1 induced increased expression of mitochondrial protective gene PGC-1alpha by
      downregulating miR-23a to inhibit hepatocyte apoptosis and also enhanced UCP2 to
      reduce apoptosis.

PMID- 26315271
TI  - Association of Fat Mass and Adipokines With Foot Pain in a Community Cohort.
AB  - OBJECTIVE: To determine, first, if fat mass index (FMI) or fat-free mass index
      (FFMI) and serum adipokines tumor necrosis factor (TNF) and interleukin-6 (IL-6)
      are associated with prevalent (stage 2) foot pain, and, second, if they are
      predictive of future (stage 3) foot pain. METHODS: A subset of participants ages
      >=50 years (n = 1,462) from the North West Adelaide Health Study were used for
      this study. Participants from this community cohort were asked in stage 2 (2004
      2006) and stage 3 (2008-2010) if they had foot pain, aching, or stiffness. In
      stage 2, serum adipokines and anthropometry were measured, while body composition
      was analyzed with dual x-ray absorptiometry. These variables, along with
      comorbidities and social history, were used in logistic regression analyses to
      determine if FMI, FFMI, and serum adipokines were associated with foot pain.
      RESULTS: Prevalent foot pain was present in 20.2% of participants, and future
      foot pain in 36.4%. Following multivariate modeling, the odds of having pain at
      stage 2 increased by 8% for each FMI unit (odds ratio [OR] 1.08, 95% confidence
      interval [95% CI] 1.04-1.12), while the odds of having pain at stage 3 increased
      by 6% for each FMI unit at stage 2 (OR 1.06, 95% CI 1.02-1.11). TNF level, IL-6
      level, and FFMI were not associated with pain. CONCLUSION: Increased FMI, but not
      body mass index, FFMI, or TNF or IL-6 level, was associated with both prevalent
      and future foot pain. These results suggest that body fat may be more important
      than body weight with respect to foot pain. The role played by other adipokines
      requires further investigation.

PMID- 26315272
TI  - Superfluidity and Chaos in low dimensional circuits.
AB  - The hallmark of superfluidity is the appearance of "vortex states" carrying a
      quantized metastable circulating current. Considering a unidirectional flow of
      particles in a ring, at first it appears that any amount of scattering will
      randomize the velocity, as in the Drude model, and eventually the ergodic steady
      state will be characterized by a vanishingly small fluctuating current. However,
      Landau and followers have shown that this is not always the case. If elementary
      excitations (e.g. phonons) have higher velocity than that of the flow, simple
      kinematic considerations imply metastability of the vortex state: the energy of
      the motion cannot dissipate into phonons. On the other hand if this Landau
      criterion is violated the circulating current can decay. Below we show that the
      standard Landau and Bogoliubov superfluidity criteria fail in low-dimensional
      circuits. Proper determination of the superfluidity regime-diagram must account
      for the crucial role of chaos, an ingredient missing from the conventional
      stability analysis. Accordingly, we find novel types of superfluidity, associated
      with irregular or chaotic or breathing vortex states. 

PMID- 26315273
TI  - Robin sequence: A European survey on current practice patterns.
AB  - To provide an overview of current practice patterns with regard to Robin sequence
      (RS) patients in Europe, a survey was conducted among European clinicians. This
      online survey consisted of different sections assessing characteristics of the
      respondent and clinic, definition, diagnosis, treatment, and follow-up. In total,
      surveys from 101 different European clinics were included in the analysis, and 56
      different RS definitions were returned. The majority (72%) of the respondents
      used a sleep study system to determine the severity of the airway obstruction. A
      total of 63% used flexible endoscopy and 16% used rigid endoscopy in the
      diagnostic process. Treatment of the airway obstruction differed considerably
      between the different countries. Prone positioning for mild airway obstruction
      was the treatment modality used most often (63%). When prone positioning was not
      successful, a nasopharyngeal airway was used (62%). Surgical therapies varied
      considerably among countries. For severe obstruction, mandibular distraction was
      performed most frequently. Three-quarters of the respondents noted the presence
      of catch-up growth in their patient population. This first European survey study
      on definition and management of RS shows that there are considerable differences
      within Europe. Therefore, we would encourage the establishment of national (and
      international) guidelines to optimize RS patient care. 

PMID- 26315274
TI  - Lower lip deformity in patients with cleft and non-cleft Class III malocclusion
      before and after orthognathic surgery.
AB  - BACKGROUND: Orthognathic surgery does not yield the same cosmetic benefits in
      patients with Class III jaw deformities associated with clefts as for patients
      without clefts. Preoperative upper lip tightness caused by cleft lip repair may
      not fully explain this difference, suggesting that a lower lip deformity is
      present. The study compared the outcomes of orthognathic surgery in patients with
      cleft and non-cleft Class III malocclusion, focusing on lip relationship.
      MATERIALS AND METHODS: The surgical records of 50 patients with Class III
      malocclusion, including 25 with and 25 without clefts, who had undergone
      orthognathic surgery, were retrospectively analyzed. Lateral cephalometric
      tracings, preoperatively and at 6 months postoperatively, were superimposed to
      analyze the soft tissue changes at seven reference points. RESULTS: At 6 months
      after surgery, there were no significant differences in skeletal location,
      whereas the soft tissues of the lower lip differed significantly between patients
      with and without cleft (p=0.002), indicating the persistence of a lower lip
      deformity in cleft patients. Moreover, the soft tissues of the lower lip receded
      in non-cleft patients and protruded in cleft patients after orthognathic surgery.
      CONCLUSION: Lower lip deformity and upper lip tightness may result in an
      unsatisfactory relationship between the upper and lower lips of patients with
      cleft-related jaw deformity after orthognathic surgery. Other factors were less
      important than the pathology of the lower lip.

PMID- 26315275
TI  - Surgical treatment of painful lesions of the inferior alveolar nerve.
AB  - Nerve-related complications are being reported with increasing frequency
      following oral and dental surgery, and typically involve the inferior alveolar
      nerve (IAN). We assess herein the etiology of neuropathic pain related to IAN
      injuries, and describe the various surgical treatment techniques available.
      Between 2007 and 2013, 19 patients were referred to the Maxillofacial Surgery
      Department of San Paolo Hospital (Milan, Italy) with pain in the area supplied by
      the IAN, which developed following endodontic treatment, oral surgery and
      maxillofacial surgery. All patients underwent IAN surgery by several different
      microsurgical procedures. Most of the patients affected by pain before surgery
      experienced complete or partial amelioration of symptoms. All patients receiving
      sural nerve grafts were pain-free 12 months after surgery. In five patients the
      operation was unsuccessful. In 78.94% of cases, a significant increase in nerve
      function was observed. Pain following IAN surgical damage may be addressed by
      microsurgery; nerve substitution with a sural nerve interpositional graft appears
      to represent the most efficacious procedure. Scar releasing, nerve decompression
      and nerve substitution using vein grafts are less effective. Removal of
      endodontic material extravasated into the mandibular canal is mandatory and
      effective in patients experiencing severe pain. Surgery should be performed
      within 12 months postoperatively, ideally during the first few weeks after
      symptoms onset. 

PMID- 26315276
TI  - Pilot investigation of the molecular discrimination of human osteoblasts from
      different bone entities.
AB  - In oral and maxillofacial surgery, autologous grafts from the iliac crest remain
      the 'gold standard' for alveolar ridge reconstruction, whereas intraoral bone
      grafts are considered in smaller defects. To date, a comparison of the osteogenic
      potential of osteoblasts with regard to their tissue origin is missing. Primary
      osteoblasts have proven useful for the investigation of the tissue-specific
      osteogenic properties. The present study compares primary human alveolar (aHOBs)
      and iliac osteoblasts (iHOBs) derived from three female patients undergoing
      routine intraoral bone grafting. Proliferation potential of the osteoblasts was
      evaluated using real-time impedance monitoring. Relative gene expression of bone
      specific biomarkers was analyzed and quantified using quantitative polymerase
      chain reactions (qPCR). Immunohistochemistry and phase contrast microscopy were
      performed, as well as alkaline phosphatase assay and alizarin red staining to
      visualize morphology and mineralization capacity. A twofold faster proliferation
      rate of aHOBs compared with iHOBs (130 h vs. 80 h) was observed. Alkaline
      phosphatase activity and alizarin red staining in both HOBs indicated similar
      mineralization capacity. Gene expression of seven genes (BMP1, CSF-1, TGFBR1,
      ICAM1, VCAM1, SPP1 and DLX5) was significantly higher in iHOB than in aHOB
      samples. These data suggest a higher osteogenic potential of osteoblasts derived
      from the iliac crest compared with primary osteoblasts from the alveolar bone and
      may lead to a better understanding of the molecular impact of bone cells from
      different bone entities on bone regeneration in alveolar ridge reconstructions.

PMID- 26315277
TI  - Soft Tissue B-Cell Lymphoma, Unclassifiable, with Features Intermediate between
      Diffuse Large B-Cell Lymphoma and Burkitt's Lymphoma Diagnosed by Fine Needle
      Aspiration Cytology.

PMID- 26315279
TI  - [Anemias].

PMID- 26315278
TI  - Symptoms of generalized anxiety disorder but not panic disorder at age 15 years
      increase the risk of depression at 18 years in the Avon Longitudinal Study of
      Parents and Children (ALSPAC) cohort study.
AB  - BACKGROUND: Generalized anxiety disorder (GAD) and panic disorder (PD) differ in
      their biology and co-morbidities. We hypothesized that GAD but not PD symptoms at
      the age of 15 years are associated with depression diagnosis at 18 years. METHOD:
      Using longitudinal data from the Avon Longitudinal Study of Parents and Children
      (ALSPAC) birth cohort we examined relationships of GAD and PD symptoms (measured
      by the Development and Well-Being Assessment) at 15 years with depression at 18
      years (by the Clinical Interview Schedule - Revised) using logistic regression.
      We excluded adolescents already depressed at 15 years and adjusted for social
      class, maternal education, birth order, gender, alcohol intake and smoking. We
      repeated these analyses following multiple imputation for missing data. RESULTS:
      In the sample with complete data (n = 2835), high and moderate GAD symptoms in
      adolescents not depressed at 15 years were associated with increased risk of
      depression at 18 years both in unadjusted analyses and adjusting for PD symptoms
      at 15 years and the above potential confounders. The adjusted odds ratio (OR) for
      depression at 18 years in adolescents with high relative to low GAD scores was
      5.2 [95% confidence interval (CI) 3.0-9.1, overall p < 0.0001]. There were no
      associations between PD symptoms and depression at 18 years in any model (high
      relative to low PD scores, adjusted OR = 1.3, 95% CI 0.3-4.8, overall p = 0.737).
      Missing data imputation strengthened the relationship of GAD symptoms with
      depression (high relative to low GAD scores, OR = 6.2, 95% CI 3.9-9.9) but those
      for PD became weaker. CONCLUSIONS: Symptoms of GAD but not PD at 15 years are
      associated with depression at 18 years. Clinicians should be aware that
      adolescents with GAD symptoms may develop depression.

PMID- 26315280
TI  - Quantification of endocytosis using a folate functionalized silica hollow
      nanoshell platform.
AB  - A quantification method to measure endocytosis was designed to assess cellular
      uptake and specificity of a targeting nanoparticle platform. A simple N 
      hydroxysuccinimide ester conjugation technique to functionalize 100-nm hollow
      silica nanoshell particles with fluorescent reporter fluorescein isothiocyanate
      and folate or polyethylene glycol (PEG) was developed. Functionalized nanoshells
      were characterized using scanning electron microscopy and transmission electron
      microscopy and the maximum amount of folate functionalized on nanoshell surfaces
      was quantified with UV-Vis spectroscopy. The extent of endocytosis by HeLa
      cervical cancer cells and human foreskin fibroblast (HFF-1) cells was
      investigated in vitro using fluorescence and confocal microscopy. A simple
      fluorescence ratio analysis was developed to quantify endocytosis versus surface
      adhesion. Nanoshells functionalized with folate showed enhanced endocytosis by
      cancer cells when compared to PEG functionalized nanoshells. Fluorescence ratio
      analyses showed that 95% of folate functionalized silica nanoshells which adhered
      to cancer cells were endocytosed, while only 27% of PEG functionalized nanoshells
      adhered to the cell surface and underwent endocytosis when functionalized with
      200 and 900  MUg , respectively. Additionally, the endocytosis of folate
      functionalized nanoshells proved to be cancer cell selective while sparing normal
      cells. The developed fluorescence ratio analysis is a simple and rapid
      verification/validation method to quantify cellular uptake between datasets by
      using an internal control for normalization.

PMID- 26315281
TI  - Disruption of beta-catenin/CBP signaling inhibits human airway epithelial
      mesenchymal transition and repair.
AB  - The epithelium of asthmatics is characterized by reduced expression of E-cadherin
      and increased expression of the basal cell markers ck-5 and p63 that is
      indicative of a relatively undifferentiated repairing epithelium. This phenotype
      correlates with increased proliferation, compromised wound healing and an
      enhanced capacity to undergo epithelial-mesenchymal transition (EMT). The
      transcription factor beta-catenin plays a vital role in epithelial cell
      differentiation and regeneration, depending on the co-factor recruited.
      Transcriptional programs driven by the beta-catenin/CBP axis are critical for
      maintaining an undifferentiated and proliferative state, whereas the beta
      catenin/p300 axis is associated with cell differentiation. We hypothesized that
      disrupting the beta-catenin/CBP signaling axis would promote epithelial
      differentiation and inhibit EMT. We treated monolayer cultures of human airway
      epithelial cells with TGFbeta1 in the presence or absence of the selective small
      molecule ICG-001 to inhibit beta-catenin/CBP signaling. We used western blots to
      assess expression of an EMT signature, CBP, p300, beta-catenin, fibronectin and
      ITGbeta1 and scratch wound assays to assess epithelial cell migration. Snai-1 and
      -2 expressions were determined using q-PCR. Exposure to TGFbeta1 induced EMT,
      characterized by reduced E-cadherin expression with increased expression of alpha
      smooth muscle actin and EDA-fibronectin. Either co-treatment or therapeutic
      administration of ICG-001 completely inhibited TGFbeta1-induced EMT. ICG-001 also
      reduced the expression of ck-5 and -19 independent of TGFbeta1. Exposure to ICG
      001 significantly inhibited epithelial cell proliferation and migration,
      coincident with a down regulation of ITGbeta1 and fibronectin expression. These
      data support our hypothesis that modulating the beta-catenin/CBP signaling axis
      plays a key role in epithelial plasticity and function. 

PMID- 26315282
TI  - Muscle Power Is an Independent Determinant of Pain and Quality of Life in Knee
      Osteoarthritis.
AB  - OBJECTIVE: This study examined the relationships between leg muscle strength,
      power, and perceived disease severity in subjects with knee osteoarthritis (OA)
      in order to determine whether dynamic leg extensor muscle power would be
      associated with pain and quality of life in knee OA. METHODS: Baseline data on
      190 subjects with knee OA (mean +/- SD age 60.2 +/- 10.4 years, body mass index
      32.7 +/- 7.2 kg/m(2) ) were obtained from a randomized controlled trial. Knee
      pain was measured using the Western Ontario and McMaster Universities
      Osteoarthritis Index, and health-related quality of life was assessed using the
      Short Form 36 (SF-36). One-repetition maximum (1RM) strength was assessed using
      the bilateral leg press, and peak muscle power was measured during 5 maximum
      voluntary velocity repetitions at 40% and 70% of 1RM. RESULTS: In univariate
      analysis, greater muscle power was significantly associated with pain (r = -0.17,
      P < 0.02) and also significantly and positively associated with SF-36 physical
      component summary (PCS) scores (r = 0.16, P < 0.05). After adjustment for
      multiple covariates, muscle power was a significant independent predictor of pain
      (P <= 0.05) and PCS scores (P <= 0.04). However, muscle strength was not an
      independent determinant of pain or quality of life (P >= 0.06). CONCLUSION:
      Muscle power is an independent determinant of pain and quality of life in knee
      OA. Compared to strength, muscle power may be a more clinically important measure
      of muscle function within this population. New trials to systematically examine
      the impact of muscle power training interventions on disease severity in knee OA
      are particularly warranted.

PMID- 26315283
TI  - Improving the effectiveness of service delivery in the public healthcare sector:
      the case of ophthalmology services in Malaysia.
AB  - BACKGROUND: Rising demand of ophthalmology care is increasingly straining
      Malaysia's public healthcare sector due to its limited human and financial
      resources. Improving the effectiveness of ophthalmology service delivery can
      promote national policy goals of population health improvement and system
      sustainability. This study examined the performance variation of public
      ophthalmology service in Malaysia, estimated the potential output gain and
      investigated several factors that might explain the differential performance.
      METHODS: Data for 2011 and 2012 on 36 ophthalmology centres operating in the
      Ministry of Health hospitals were used in this analysis. We first consulted a
      panel of ophthalmology service managers to understand the production of
      ophthalmology services and to verify the production model. We then assessed the
      relative performance of these centres using Data Envelopment Analysis (DEA).
      Efficiency scores (ES) were decomposed into technical, scale, and congestion
      component. Potential increase in service output was estimated. Sensitivity
      analysis of model changes was performed and stability of the result was assessed
      using bootstrap approach. Second stage Tobit regression was conducted to
      determine if hospital type, availability of day services and population
      characteristics were related to the DEA scores. RESULTS: In 2011, 33% of the
      ophthalmology centres were found to have ES > 1 (mean ES = 1.10). Potential
      output gains were 10% (SE +/- 2.92), 7.4% (SE +/- 2.06), 6.9% (SE +/- 1.97) if
      the centres could overcome their technical, scale and congestion inefficiencies.
      More centres moved to the performance frontier in 2012 (mean ES = 1.07), with
      lower potential output gain. The model used has good stability. Robustness checks
      show that the DEA correctly identified low performing centres. Being in state
      hospital was significantly associated with better performance. CONCLUSIONS: Using
      DEA to benchmarking service performance of ophthalmology care could provide
      insights for policy makers and service managers to intuitively visualise the
      overall performance of resource use in an otherwise difficult to assess scenario.
      The considerable potential output gain estimated indicates that effort should be
      invested to understand what drove the performance variation and optimise them.
      Similar performance assessment should be undertaken for other healthcare services
      in the country in order to work towards a sustainable health system.

PMID- 26315285
TI  - Live attenuated herpes zoster vaccine for HIV-infected adults.
AB  - OBJECTIVES: Multiple guidelines exist for the use of live viral vaccines for
      measles-mumps-rubella (MMR), varicella and yellow fever in people with HIV
      infections, but these guidelines do not make recommendations regarding live
      attenuated herpes zoster vaccine (LAHZV), which is approved for people over 50
      years in the general population. LAHZV is made with the same virus used in
      varicella vaccine. The incidence of herpes zoster remains increased in people
      with HIV infection, even when on suppressive antiretroviral therapy, and a
      growing proportion of HIV-infected patients are over 50 years of age. The purpose
      of this article is to review the use of varicella vaccine and LAHZV in people
      with HIV infection and to make recommendations about the use of LAHZV in adults
      with HIV infection. METHODS: A PubMed search was undertaken using the terms
      'herpes zoster AND HIV' and 'varicella AND HIV'. Reference lists were also
      reviewed for pertinent citations. RESULTS: Varicella vaccine is recommended in
      varicella-susceptible adults, as long as they have a CD4 count > 200 cells/MUL,
      the same CD4 threshold used for MMR and yellow fever vaccines. No transmission of
      vaccine strain Varicella zoster virus has been documented in people with HIV
      infections with a CD4 count above this threshold. LAHZV was administered to 295
      HIV-infected adults with a CD4 count > 200 cells/MUL, and was safe and
      immunogenic with no cases of vaccine strain infection. CONCLUSIONS: It is
      recommended that LAHZV be administered to HIV-infected adults with a CD4 count
      above 200 cells/MUL, the same CD4 threshold used for other live attenuated viral
      vaccines.

PMID- 26315284
TI  - Effect of integrated infectious disease training and on-site support on the
      management of childhood illnesses in Uganda: a cluster randomized trial.
AB  - BACKGROUND: The Integrated Infectious Disease Capacity-Building Evaluation
      (IDCAP) was designed to test the effects of two interventions, Integrated
      Management of Infectious Disease (IMID) training and on-site support (OSS), on
      clinical practice of mid-level practitioners. This article reports the effects of
      these interventions on clinical practice in management of common childhood
      illnesses. METHODS: Two trainees from each of 36 health facilities participated
      in the IMID training. IMID was a three-week core course, two one-week boost
      courses, and distance learning over nine months. Eighteen of the 36 health
      facilities were then randomly assigned to arm A, and participated in OSS, while
      the other 18 health facilities assigned to arm B did not. Clinical faculty
      assessed trainee practice on clinical practice of six sets of tasks: patient
      history, physical examination, laboratory tests, diagnosis, treatment, and
      patient/caregiver education. The effects of IMID were measured by the post/pre
      adjusted relative risk (aRR) of appropriate practice in arm B. The incremental
      effects of OSS were measured by the adjusted ratio of relative risks (aRRR) in
      arm A compared to arm B. All hypotheses were tested at a 5% level of
      significance. RESULTS: Patient samples were comparable across arms at baseline
      and endline. The majority of children were aged under five years; 84% at baseline
      and 97% at endline. The effects of IMID on patient history (aRR = 1.12; 95% CI =
      1.04-1.21) and physical examination (aRR = 1.40; 95% CI = 1.16-1.68) tasks were
      statistically significant. OSS was associated with incremental improvement in
      patient history (aRRR = 1.18; 95% CI = 1.06-1.31), and physical examination (aRRR
      = 1.27; 95% CI = 1.02-1.59) tasks. Improvements in laboratory testing, diagnosis,
      treatment, and patient/caregiver education were not statistically significant.
      CONCLUSION: IMID training was associated with improved patient history taking and
      physical examination, and OSS further improved these clinical practices. On-site
      training and continuous quality improvement activities support transfer of
      learning to practice among mid-level practitioners.

PMID- 26315287
TI  - Xenotransplantation literature update, July-August 2015.

PMID- 26315286
TI  - Increased SYK activity is associated with unfavorable outcome among patients with
      acute myeloid leukemia.
AB  - Recent discoveries have led to the testing of novel targeted therapies for the
      treatment of acute myeloid leukemia (AML). To better inform the results of
      clinical trials, there is a need to identify and systematically assess biomarkers
      of response and pharmacodynamic markers of successful target engagement. Spleen
      tyrosine kinase (SYK) is a candidate therapeutic target in AML. Small-molecule
      inhibitors of SYK induce AML differentiation and impair leukemia progression in
      preclinical studies. However, tools to predict response to SYK inhibition and to
      routinely evaluate SYK activation in primary patient samples have been lacking.
      In this study we quantified phosphorylated SYK (P-SYK) in AML cell lines and
      establish that increasing levels of baseline P-SYK are correlated with an
      increasing sensitivity to small-molecule inhibitors targeting SYK. In addition,
      we found that pharmacological inhibition of SYK activity extinguishes P-SYK
      expression as detected by an immunohistochemical (IHC) test. Quantitative
      analysis of P-SYK expression by the IHC test in a series of 70 primary bone
      marrow biopsy specimens revealed a spectrum of P-SYK expression across AML cases
      and that high P-SYK expression is associated with unfavourable outcome
      independent of age, cytogenetics, and white blood cell count. This study thus
      establishes P-SYK as a critical biomarker in AML that identifies tumors sensitive
      to SYK inhibition, identifies an at-risk patient population, and allows for the
      monitoring of target inhibition during treatment. 

PMID- 26315288
TI  - Photo-thermal effect enhances the efficiency of radiotherapy using Arg-Gly-Asp
      peptides-conjugated gold nanorods that target alphavbeta3 in melanoma cancer
      cells.
AB  - BACKGROUND: Thermotherapy has been known to be one of the most effective
      adjuvants to radiotherapy (RT) in cancer treatment, but it is not widely
      implemented clinically due to some limitations, such as, inadequate temperature
      concentrations to the tumor tissue, nonspecific and non-uniform distribution of
      heat. So we constructed arginine-glycine-aspartate peptides-conjugated gold
      nanorods (RGD-GNRs) that target the alpha(v) beta(3) Integrin (alphavbeta3) and
      investigate whether the photo-thermal effect of RGD-GNRs by near infrared
      radiation (NIR) could enhance the efficiency of RT in melanoma cancer cells.
      RESULTS: RGD-GNRs could be seen both on the surface of the cell membranes and
      cytoplasm of A375 cells with high expression of alphavbeta3. After exposed to 808
      nm NIR, RGD-GNRs with various concentrations could be rapidly heated up. Compared
      to other treatments, flow cytometric analysis indicated that RT + NIR + RGD-GNRs
      increased apoptosis (p < 0.001) and decreased the proportion of cells in the more
      radioresistant S phase (p = 0.014). Treated with NIR + RGD-GNRs, the
      radiosensitivity was also significantly enhanced (DMFSF2: 1.41). CONCLUSION:
      Results of the current study showed the feasibility of using RGD-GNRs for
      synergetic RT with photo-thermal therapy. And it would greatly benefit the
      therapeutic effects of refractory or recurrent malignant cancers.

PMID- 26315289
TI  - Evaluation of older driver head functional range of motion using portable
      immersive virtual reality.
AB  - BACKGROUND: The number of drivers over 65 years of age continues to increase.
      Although neck rotation range has been identified as a factor associated with self
      reported crash history in older drivers, it was not consistently reported as
      indicators of older driver performance or crashes across previous studies. It is
      likely that drivers use neck and trunk rotation when driving, and therefore the
      functional range of motion (ROM) (i.e. overall rotation used during a task) of
      older drivers should be further examined. OBJECTIVE: Evaluate older driver
      performance in an immersive virtual reality, simulated, dynamic driving blind
      spot target detection task. METHODS: A cross-sectional laboratory study recruited
      twenty-six licensed drivers (14 young between 18 and 35 years, and 12 older
      between 65 to 75 years) from the local community. Participants were asked to
      detect targets by performing blind spot check movements while neck and trunk
      rotation was tracked. Functional ROM, target detection success, and time to
      detection were analyzed. RESULTS: In addition to neck rotation, older and younger
      drivers on average rotated their trunks 9.96 degrees  and 18.04 degrees ,
      respectively. The younger drivers generally demonstrated 15.6 degrees  greater
      functional ROM (p<.001), were nearly twice as successful in target detection due
      to target location (p=.008), and had 0.46 s less target detection time (p=.016)
      than the older drivers. CONCLUSION: Assessing older driver functional ROM may
      provide more comprehensive assessment of driving ability than neck ROM. Target
      detection success and time to detection may also be part of the aging process as
      these measures differed between driver groups.

PMID- 26315290
TI  - Of mice, pigs and humans: An analysis of mitochondrial phospholipids from mammals
      with very different maximal lifespans.
AB  - The maximal lifespan (MLS) of mammals is inversely correlated with the
      peroxidation index, a measure of the proportion and level of unsaturation of
      polyunsaturated fatty acids (PUFA) in membranes. This relationship is likely
      related to the fact that PUFA are highly susceptible to damage by peroxidation.
      Previous comparative work has examined membrane composition at the level of fatty
      acids, and relatively little is known regarding the distribution of PUFA across
      phospholipid classes or phospholipid molecules. In addition, data for humans is
      extremely rare in this area. Here we present the first shotgun lipidomics
      analysis of mitochondrial membranes and the peroxidation index of skeletal
      muscle, liver, and brain in three mammals that span the range of mammalian
      longevity. The species compared were mice (MLS of 4 years), pigs (MLS of 27
      years), and humans (MLS of 122 years). Mouse mitochondria contained highly
      unsaturated PUFA in all phospholipid classes. Human mitochondria had lower PUFA
      content and a lower degree of unsaturation of PUFA. Pig mitochondria shared
      characteristics of both mice and humans. We found that membrane susceptibility to
      peroxidation was primarily determined by a limited number of phospholipid
      molecules that differed between both tissues and species.

PMID- 26315291
TI  - Uveitis in juvenile idiopathic arthritis: recent therapeutic advances.
AB  - Uveitis is a common association of juvenile idiopathic arthritis (JIA) that has
      previously been characterized by poor visual prognosis with limited options for
      effective treatment. Since corticosteroid treatment is not a preferred long-term
      option for most patients with this condition, systemic immunosuppressive therapy
      is frequently employed. The medical options for the treatment of JIA-associated
      uveitis have recently expanded beyond conventional immunosuppressive drugs to the
      biological agents. The biological drugs that are most commonly employed for JIA
      associated uveitis are the tumor necrosis factor-alpha inhibitors. Other
      biological agents that have been used to treat the disease include drugs that
      target cytokine receptors, lymphocyte antigens and lymphocyte co-stimulation
      signals. This Mini Review highlights recent developments in the medical treatment
      of JIA-associated uveitis. 

PMID- 26315292
TI  - Laparoscopic surgery for esophageal achalasia: Multiport vs single-incision
      approach.
AB  - INTRODUCTION: SILS can potentially improve aesthetic outcomes without adversely
      affecting treatment outcomes, but these outcomes are uncertain in laparoscopic
      Heller-Dor surgery. We determined if the degree of patient satisfaction with
      aesthetic outcomes progressed with the equivalent treatment outcomes after the
      introduction of a single-incision approach to laparoscopic Heller-Dor surgery.
      METHODS: We retrospectively reviewed 20 consecutive esophageal achalasia patients
      (multiport approach, n = 10; single-incision approach, n = 10) and assessed the
      treatment outcomes and patient satisfaction with the aesthetic outcomes. RESULTS:
      In the single-incision approach, thin supportive devices were routinely used to
      gain exposure to the esophageal hiatus. No statistically significant differences
      in the operating time (210.2 +/- 28.8 vs 223.5 +/- 46.3 min; P = 0.4503) or blood
      loss (14.0 +/- 31.7 vs 16.0 +/- 17.8 mL; P = 0.8637) were detected between the
      multiport and single-incision approaches. We experienced no intraoperative
      complications. Mild dysphagia, which resolved spontaneously, was noted
      postoperatively in one patient treated with the multiport approach. The reduction
      rate of the maximum lower esophageal sphincter pressure was 25.1 +/- 34.4% for
      the multiport approach and 21.8 +/- 19.2% for the single-incision approach (P =
      0.8266). Patient satisfaction with aesthetic outcomes was greater for the single
      incision approach than for the multiport approach. CONCLUSION: When single
      incision laparoscopic Heller-Dor surgery was performed adequately and combined
      with the use of thin supportive devices, patient satisfaction with the aesthetic
      outcomes was higher and treatment outcomes were equivalent to those of the
      multiport approach.

PMID- 26315293
TI  - Ovarian actions of resveratrol.
AB  - Resveratrol, a natural polyphenol found in grapes, berries, and medicinal plants,
      exhibits antioxidant and anti-inflammatory activities and has been proposed to be
      a longevity-prolonging agent. There is also growing evidence that resveratrol has
      cardioprotective properties and beneficial effects on both glucose and lipid
      metabolism. Recently, several studies have examined the use of resveratrol as a
      therapeutic agent to treat numerous pathological and metabolic disorders. Herein,
      we present insights into the mechanisms of action, biological effects, and
      current evidence of actions of resveratrol on the ovary. In vitro, resveratrol
      inhibits proliferation and androgen production by theca-interstitial cells.
      Resveratrol also exerts a cytostatic, but not cytotoxic, effect on granulosa
      cells, while decreasing aromatization and vascular endothelial growth factor
      expression. In vivo, resveratrol treatment reduced the size of adipocytes and
      improved estrus cyclicity in the previously acyclic rat model of polycystic ovary
      syndrome (PCOS). In addition, resveratrol increased the ovarian follicular
      reserve and prolonged the ovarian life span in rats. Taken together, resveratrol
      emerges as a potential therapeutic agent to treat conditions associated with
      androgen excess, such as PCOS. The efficacy of resveratrol in the treatment of
      gynecological conditions requires further investigation. 

PMID- 26315294
TI  - Resveratrol: challenges in analyzing its biological effects.
AB  - Testing the biological activities of a dietary compound like resveratrol presents
      various challenges, which are highlighted in this commentary, with some suggested
      direction for future research, focusing on five challenges: (1) many different
      cellular effects are observed for resveratrol, but it is not known whether they
      arise from one point of action (or a few) or whether resveratrol is non-specific
      in its action; (2) the health-promotion effect of dietary resveratrol is likely a
      combinatory effect of various bioactive components in the mixture (diet); (3) the
      known cell biological response to resveratrol is presently based on exposure to
      short-term high levels, and better in vitro analyses have to be developed; (4)
      the actual level of resveratrol and resveratrol metabolites present in vitro and
      in vivo during experiments may be over- and underestimated, respectively, because
      resveratrol is not very soluble in water; and (5) only a few small clinical
      studies have been published to date, focusing on the therapeutic effects of
      resveratrol. Further, clinical trials addressing the disease-preventive effects
      are especially challenging. 

PMID- 26315295
TI  - Resveratrol and health from a consumer perspective: perception, attitude, and
      adoption of a new functional ingredient.
AB  - Resveratrol is an ingredient widely researched, with growing evidence of health
      promoting effects. However, the reactions of supplement or food consumers to
      resveratrol has not been researched, and the ingredient is yet unknown to most
      consumers. We used respective literature and our own resveratrol consumer studies
      with Danish and U.S. consumers to look at current findings and future research
      directions for three questions. (1) Which factors determine consumer interest in
      a yet unknown functional ingredient such as resveratrol? (2) How should
      resveratrol be marketed as a new functional ingredient to be understood and
      favorably perceived? (3) What could be the effects of adoption of an ingredient
      such as resveratrol on the healthy lifestyle of a consumer? Literature and first
      results indicate that personal relevance and familiarity are crucial factors;
      however, consumers show little interest in resveratrol and lack relevant
      knowledge, especially in Denmark. Favorable attitudes were explained by health
      outcome expectations, use of complementary and alternative medicine, and interest
      in the indulgence dimension of food. Nonscientifically phrased communication led
      to more favorable attitudes in Danish consumers; scientifically phrased
      communication, though, made U.S. consumers more likely to retain favorable
      attitudes in the presence of contradictory evidence. We discuss future research
      directions in different cultural backgrounds and market contexts and for
      different foods. 

PMID- 26315296
TI  - Introduction to Resveratrol and Health: 3rd International Conference.

PMID- 26315298
TI  - The Carlin Effect.

PMID- 26315297
TI  - Different Phenotypes of Non-Steroidal Anti-Inflammatory Drug Hypersensitivity
      during Childhood.
AB  - BACKGROUND: Although non-steroidal anti-inflammatory drug hypersensitivity (NSAID
      H) has been widely studied in adults, there is still a lack of data regarding the
      features and phenotypes of NSAID-H in children. Our aim was to define risk
      factors and different phenotypes according to clinical patterns. METHODS:
      Patients with a history of reaction to any NSAIDs referred between January 2012
      and October 2014 were included. After completing a European Network for Drug
      Allergy (ENDA) questionnaire, initial skin and/or oral provocation tests (OPTs)
      were performed for the offending drug. Additional OPTs were done with aspirin in
      case of NSAID-H to determine cross-reactivity. NSAID-hypersensitive patients were
      defined as being either a selective responder (SR) or cross-intolerant (CI) and
      further categorized according to either the ENDA/GA2LEN classification or an
      alternative scheme by Caimmi et al. [Int Arch Allergy Immunol 2012;159:306-312].
      RESULTS: Among 121 patients [58.7% male, average age 7.8 years (4.7-10.8)] with
      161 NSAID-related reactions, 110 patients with 148 reactions were assessed. NSAID
      H was diagnosed in 30 (27%) patients with 37 (25%) reactions. Multivariate
      regression analysis revealed that an immediate-type reaction and respiratory
      symptoms during the reaction increased the risk of a reproducible NSAID-related
      reaction (OR 3.508, 95% CI 1.42-8.7, p = 0.007; OR 3.951, 95% CI 1.33-11.77, p =
      0.014, respectively). Additional OPTs revealed 13 SRs and 14 CIs. A family
      history of allergic disease was more frequent in CIs compared to SRs (57.1 vs.
      15.4%, p = 0.031). Reactions belonging to CIs were more frequently characterized
      by angioedema compared to those of SRs (81.3 vs. 46.2%, p = 0.019). SRs and CIs
      were further classified as single NSAID-induced urticaria/angioedema and/or
      anaphylaxis (n = 13), NSAID-induced urticaria/angioedema (n = 7), NSAID
      exacerbated cutaneous disease (n = 2) and NSAID-exacerbated respiratory disease
      (n = 1). Four CIs could not be categorized according to either classification
      system. One SR could not be categorized according to ENDA/GA2LEN. CONCLUSION:
      During childhood, NSAID-H exhibits different phenotypes and the majority of them
      can be categorized with current classification systems; however, classifications
      based on adult data may not exactly fit NSAID-H in paediatric patients.

PMID- 26315299
TI  - HMGN5 blockade by siRNA enhances apoptosis, suppresses invasion and increases
      chemosensitivity to temozolomide in meningiomas.
AB  - The high-mobility group nucleosome-binding protein-5 (HMGN5) is frequently
      overexpressed in various malignant cancers. However, the potential correlation
      between HMGN5 and prognosis in patients with meningiomas remains unknown. In the
      present study, we explored the expression of HMGN5 in meningiomas with
      immunohistochemistry and correlated the results to the patient outcome. Potential
      effects of HMGN5 on tumor growth, apoptosis and invasion were also examined in
      representative cell lines (IOMM-Lee and CH157) by downregulating HMGN5 with RNA
      interference (siRNA). We demonstrate that there is a positive association between
      HMGN5 expression and meningioma histological grade. Statistical analysis reveals
      that lower HMGN5 expression predict lower meningioma recurrence. In addition,
      downregulation of HMGN5 inhibits IOMM-Lee and CH157 cell proliferation, enhances
      cell apoptosis and suppresses tumor invasion. Our results further revealed that
      HMGN5 inhibition decreased P-glycoprotein (MDR-1) expression without affecting
      multidrug resistance associated proteins 1 (MRP-1) expression to increase
      chemosensitivity to temozolomide (TMZ) of meningioma cells. Collectively, this
      study indicates that HMGN5 is a novel target for developing effective therapeutic
      strategies for malignant meningiomas.

PMID- 26315300
TI  - Amelioration of experimental arthritis by intra-articular injection of an
      epidermal growth factor receptor tyrosine kinase inhibitor.
AB  - OBJECTIVES: Selectively targeting signalling pathways represents a promising
      pharmacological approach in rheumatoid arthritis (RA). Abundant levels of
      epidermal growth factor receptor (EGFR) are expressed in the synovial lining
      layers, and the anti-arthritis effect of erlotinib and lapatinib, small-molecule
      EGFR tyrosine kinase inhibitors (TKIs), has been demonstrated through the
      systemic administration on experimental arthritis models. Nevertheless, their
      therapeutic responses by the intra-articular (i.a.) route remain to be explored
      in rheumatoid joint. METHODS: The administration of an EGFR TKI (a gefitinib
      analogue) was explored in two in vivo models of collagen-induced arthritis (CIA)
      and in vitro experiments by using synovial fibroblasts (SF) from RA patients and
      CIA rats. RESULTS: There was a significant reduction of arthritis scores in CIA
      mice receiving the daily intraperitoneal injection. After the onset of arthritis
      in CIA rats, ankle joints receiving a single i.a. injection had significant lower
      articular indexes with reduced synovial inflammation, pannus formation and
      erosion on cartilage and bone as well as total histological scores by
      histopathological analyses. In CIASF or RASF, upon in vitro human EGF
      stimulation, there was a dose-dependent increase in cell proliferation and Akt
      activation with suppressed responses under the EGFR TKI treatment. CONCLUSIONS:
      These findings demonstrate the effect of i.a. injection of an EGFR TKI on
      amelioration of rheumatoid joint through the suppression of synovial
      inflammation, pannus formation and erosion on cartilage and bone in experimental
      arthritis, implicating targeting the i.a. EGFR signalling transduction as a
      pharmacological strategy.

PMID- 26315302
TI  - Correlation of the molecular structure of host materials with lifetime and
      efficiency of blue phosphorescent organic light-emitting diodes.
AB  - Bicarbazole derivatives, 9,9'-bis(dibenzo[b,d]thiophen-2-yl)-9H,9'H-3,3'
      bicarbazole (BCzDBT), 9,9'-bis(dibenzo[b,d]furan-2-yl)-9H,9'H-3,3'-bicarbazole
      (BCzDBF), and 9,9'-di([1,1'-biphenyl]-3-yl)-9H,9'H-3,3'-bicarbazole (BCzBP), were
      designed and examined as the hole transport type host materials of the tris[1
      (2,4-diisopropyldibenzo[b,d]furan-3-yl)-2-phenylimidazole] (Ir(dbi)3) blue
      triplet emitter. BCzDBT performed better than BCzDBF and BCzBP as the hosts of
      Ir(dbi)3 and could demonstrate 24.8% quantum efficiency and long lifetime in the
      blue phosphorescent devices. Strong hole carrying properties of the bicarbazole
      derivatives were proposed as the main factors for the high quantum efficiency of
      the BCzDBT devices, and thermal and chemical stability of BCzDBT were suggested
      as crucial factors for the long lifetime of the BCzDBT devices. 

PMID- 26315301
TI  - From gene discovery to new biological mechanisms: heparanases and congenital
      urinary bladder disease.
AB  - We present a scientific investigation into the pathogenesis of a urinary bladder
      disease. The disease in question is called urofacial syndrome (UFS), a congenital
      condition inherited in an autosomal recessive manner. UFS features incomplete
      urinary bladder emptying and vesicoureteric reflux, with a high risk of recurrent
      urosepsis and end-stage renal disease. The story starts from a human genomic
      perspective, then proceeds through experiments that seek to determine the roles
      of the implicated molecules in embryonic frogs and newborn mice. A future aim
      would be to use such biological knowledge to intelligently choose novel therapies
      for UFS. We focus on heparanase proteins and the peripheral nervous system,
      molecules and tissues that appear to be key players in the pathogenesis of UFS
      and therefore must also be critical for functional differentiation of healthy
      bladders. These considerations allow the envisioning of novel biological
      treatments, although the potential difficulties of targeting the developing
      bladder in vivo should not be underestimated.

PMID- 26315303
TI  - Effects of Zinc Supplementation on Endocrine Outcomes in Women with Polycystic
      Ovary Syndrome: a Randomized, Double-Blind, Placebo-Controlled Trial.
AB  - The current study was conducted to evaluate the effects of zinc supplementation
      on endocrine outcomes, biomarkers of inflammation, and oxidative stress in
      patients with polycystic ovary syndrome (PCOS). This study was a randomized
      double-blind, placebo-controlled trial. Forty-eight women (18-40 years) with PCOS
      diagnosed according to Rotterdam criteria were randomly assigned to receive
      either 220 mg zinc sulfate (containing 50 mg zinc) (group 1; n = 24) and/or
      placebo (group 2; n = 24) for 8 weeks. Hormonal profiles, biomarkers of
      inflammation, and oxidative stress were measured at study baseline and after 8
      week intervention. After 8 weeks of intervention, alopecia (41.7 vs. 12.5%, P =
      0.02) decreased compared with the placebo. Additionally, patients who received
      zinc supplements had significantly decreased hirsutism (modified Ferriman-Gallwey
      scores) (-1.71 +/- 0.99 vs. -0.29 +/- 0.95, P < 0.001) and plasma malondialdehyde
      (MDA) levels (-0.09 +/- 1.31 vs. +2.34 +/- 5.53 MUmol/L, P = 0.04) compared with
      the placebo. A trend toward a significant effect of zinc intake on reducing high
      sensitivity C-reactive protein (hs-CRP) levels (P = 0.06) was also observed. We
      did observe no significant changes of zinc supplementation on hormonal profiles,
      inflammatory cytokines, and other biomarkers of oxidative stress. In conclusion,
      using 50 mg/day elemental zinc for 8 weeks among PCOS women had beneficial
      effects on alopecia, hirsutism, and plasma MDA levels; however, it did not affect
      hormonal profiles, inflammatory cytokines, and other biomarkers of oxidative
      stress.

PMID- 26315304
TI  - Environmental Lead (Pb) Exposure Versus Fatty Acid Content in Blood and Milk of
      the Mother and in the Blood of Newborn Children.
AB  - Significant progress in understanding the effects of the neurotoxic action of
      lead (Pb) in young organisms had led to reduction of "safe" level in the blood
      (Pb-B) to 5 MUg/dL in children and pregnant women. Prolonged exposure to
      relatively low levels of Pb, generally asymptomatic and subclinical (i.e.,
      microintoxication), is currently the dominant form of environmental poisoning,
      and its negative effects on health may appear after many years, e.g., secondary
      contamination from Pb bone deposits released in pregnancy. Therefore, the aim of
      this study was to investigate the effect of environmental exposure (urban areas)
      of mothers to Pb, on its levels in their milk and blood and in the blood of
      newborns. Moreover, the aim was to determine the fatty acid profile in the
      mothers' blood and milk and in the blood of newborns. We also wanted to find if
      infant birth weight depends on Pb blood levels, as well as on Pb and fatty acid
      levels in the blood and milk of the mothers. Finally, we examined if the mothers'
      weight and body mass index (BMI) before pregnancy influenced the concentration of
      Pb and fatty acid profile in the blood and milk of mothers and in the blood of
      their children. Analysis of fatty acids elaidic (C18:1, 9t), oleic (C18:1, 9c),
      vaccenic (C18:1, 11t), cis-vaccenic (C18:1, 11c), linoleic (C18:2, cis), gamma
      linolenic (C18:3, n-6), alpha-linolenic (C18:3, n-3), arachidonic (C20:4, n-6),
      eicosapentaenoic (C20:5, n-3), and docosahexaenoic (C22:6, n-3) was conducted by
      gas chromatography. The concentration of Pb in the whole blood and milk were
      determined by atomic absorption spectrometry with graphite furnace atomization
      and Zeeman correction. Our study established a significant and strong correlation
      between the content of Pb in the blood of the mother and the child. This supports
      the assumption that the transport of Pb through the placenta is neither regulated
      nor selective. Environmental maternal exposure to lead resulting in Pb-B levels
      considered safe for pregnant women had no effect on infant birth weight, the
      concentration of fatty acids in the blood and milk of mothers, or in the blood of
      newborns. Mothers' weight and BMI before pregnancy had no effect on the
      concentration of Pb and studied fatty acid profile. 

PMID- 26315305
TI  - Effects of Imbalance in Trace Element on Thyroid Gland from Moroccan Children.
AB  - The major environmental factor that determines goiter prevalence is iodine
      status. However, other trace elements like selenium and zinc can influence the
      thyroid function. Hair samples (n = 68) were collected from goitrous and non
      goitrous children aged 8-12 years living in the area of Al Haouz Marrakech
      (Morocco). Trace element concentrations (Cr, Fe, Mg, Zn, Se, I) in hair were
      measured using flame atomic absorption spectroscopy, graphite furnace atomic
      absorption spectroscopy, and inductively coupled plasma mass spectrometry.
      Difference in the mean concentration of each trace element between groups was
      determined by ANOVA test. The mean concentration levels of I, Se, and Zn for
      goitrous children were lower and were similar to the mean concentrations reported
      in the literature for subjects with goiter. The regression results gave us a
      better model that revealed significant positive relations between thyroid volume
      and Zn contents and significant negative relation with I and Se. The overall
      findings of the present study revealed that the actual factors of thyroid gland
      volume increase are I and Se deficiency. This work could shed some light on the
      effects of trace elements-other than iodine-on the thyroid disorders.

PMID- 26315306
TI  - Characterization of Selenoprotein M and Its Response to Selenium Deficiency in
      Chicken Brain.
AB  - Selenoprotein M (SelM) may function as thiol disulfide oxidoreductase that
      participates in the formation of disulfide bonds and can be implicated in calcium
      responses. SelM may have a functional role in catalyzing free radicals and has
      been associated with Alzheimer's disease (AD). However, studies of SelM in
      chicken remain very limited. In this study, two groups of day-old broiler chicks
      (n = 40/group) were fed a corn-soy basal diet (BD, 13 MUg Se/kg) and BD
      supplemented with Se (as sodium selenite) at 0.3 mg/kg. The brain was collected
      at 14, 21, 28, and 42 days of age. We performed a sequence analysis and predicted
      the structure and function of SelM. We also investigated the effects of Se
      deficiency on the expression of Selt, Selw, and Selm and the Se status in the
      chicken brain. The results show that Se deficiency induced the lower (P < 0.05)
      Se content, glutathione peroxidase (GPx), and catalase (CAT) activities;
      increased (P < 0.05) malondialdehyde (MDA) content; and reduced (P < 0.05) the
      expression of Selm messenger RNA (mRNA) and protein abundance of SelM in the
      brain. However, there were no significant brain Selt and Selw mRNA levels by
      dietary Se deficiency in chicks. The different regulations of these three redox
      (Rdx) protein expressions by Se deficiency represent a novel finding of the
      present study. Our results demonstrated that SelM may have an important role in
      protecting against oxidative damage in the brain of chicken, which might shed
      light on the role of SelM in human neurodegenerative disease. More studies are
      needed to confirm our conclusion.

PMID- 26315307
TI  - An Indoxyl-Based Strategy for the Synthesis of Indolines and Indolenines.
AB  - An indoxyl-based strategy for the synthesis of indolines and indolenines via
      unprecedented aza-pinacol and aza-semipinacol rearrangements was developed. This
      method provides direct access to the core structures of several classes of indole
      alkaloids. The synthetic utility was demonstrated by the divergent synthesis of
      an array of functionalized polycyclic structures from a common intermediate and
      the formal total synthesis of the indoline natural product minfiensine. The
      reversed reactivity of indoxyl as a building block compared to that of indole
      offers a conceptually distinct disconnection strategy for indoline- and
      indolenine-containing heterocycles and natural products. 

PMID- 26315308
TI  - Sex-related alcohol expectancies and high-risk sexual behaviour among drinking
      adults in Kampala, Uganda.
AB  - Alcohol consumption, a risk factor for HIV transmission in sub-Saharan Africa, is
      considered high in Uganda. A cross sectional study was conducted to determine
      whether sex-related expectations about the effects of alcohol explain the
      association between alcohol use and risky sexual behaviours in a population-based
      sample of adults in Kampala. Associations between alcohol use (current and higher
      risk drinking) and high-risk sexual behaviours (multiple regular partners and
      casual sex) were tested. In age-sex-adjusted models, having multiple regular
      partners was associated with current drinking (odds ratio [OR] = 2.76, 95%
      confidence intervals [CIs] = 1.15, 6.63) and higher risk drinking (OR = 3.35, 95%
      CI = 1.28, 8.71). Associations were similar but not statistically significant for
      having a causal sex partner. Sex-related alcohol outcome expectancy was
      associated with both alcohol use and high-risk sexual behaviour and attenuated
      relationships between multiple regular partners and both current drinking (OR =
      1.94, 95% CI = 0.57, 6.73) and higher risk drinking (OR = 2.44, 95% CI = 0.68,
      8.80). In this setting sexual behaviours related with alcohol consumption were
      explained, in part, by sex-related expectations about the effects of alcohol.
      These expectations could be an important component to target in HIV education
      campaigns. 

PMID- 26315309
TI  - Liposomal treatment of xerostomia, odor, and taste abnormalities in patients with
      head and neck cancer.
AB  - BACKGROUND: Smell and taste disorders, sicca symptoms, can be detected in
      patients with head and neck cancer. The purpose of this study was to assess the
      utility of local liposomal application in the treatment of patients with head and
      neck cancers. METHODS: Ninety-eight patients with head and neck cancer were
      included in this study. The groups were defined as: group 1 = only surgery; group
      2 = surgery + adjuvant radiochemotherapy; and group 3 = primarily
      radiochemotherapy. All patients had finished cancer treatment and received
      liposomal sprays for the nose and mouth for 2 months (LipoNasal, LipoSaliva;
      Optima Pharmaceutical GmbH, Germany) and suffered from taste and smell disorders.
      We performed tests with "Sniffin' Sticks," "Taste Strips," and a xerostomia
      questionnaire before and after treatment. RESULTS: After application of
      liposomes, patients demonstrated a statistically significant increase in smell
      and taste, and reduced xerostomia. CONCLUSION: Our results demonstrate that using
      nonpharmaceutical liposomal sprays improve smell, taste, and symptoms of
      xerostomia in patients with head and neck cancer. (c) 2015 Wiley Periodicals,
      Inc. Head Neck 38: E1232-E1237, 2016.

PMID- 26315310
TI  - Scientific Interests of 21st Century Clinical Oral Implant Research: Topical
      Trend Analysis.
AB  - BACKGROUND: Discrimination between ongoing and solved research questions may help
      to distinguish established dogmas from evidence-based implant dentistry. PURPOSE:
      The purpose of this study was to investigate topics of interest in the field of
      oral implant science and evolving thematic trends in clinical studies during the
      last decade. MATERIALS AND METHODS: Electronic and manual searches of English
      literature were performed to identify clinical studies on oral implants. Out of
      15,695 publications screened, 2,875 clinical investigations were included.
      RESULTS: Among the most prevalent topics were immediate loading (14.3%), bone
      substitutes (11.6%), lateral sinus grafting (10.7%), implant overdentures
      (10.5%), single-tooth implant crowns (8.8%), cross-arch implant bridges (8.0%),
      immediate implant placement (7.5%), implant surfaces (7.0%), simultaneous implant
      placement and augmentation (6.4%) as well as guided bone regeneration (5.3%).
      Significant increase of scientific interest was seen in immediate loading (+6.3%,
      p < .001), platform switching (+2.9%, p < 0.001), lateral sinus grafting (+2.3%,
      p = .024), flapless implant surgery (+2.2%, p < 0.001), and guided implant
      surgery (+1.9%, p = .011), while research on implant overdentures (-6.6%, p =
      .033) and tooth-to-implant connection (-2.5%, p = .010) was on the decline.
      CONCLUSIONS: Literature coverage, since the beginning of the 21st century, has
      seen greater focus on surgical topics compared to prosthodontic issues (p = .005)
      while only few topics experienced decrease of interest indicating scientific
      consensus.

PMID- 26315311
TI  - Difficulties in emotion regulation differentiate depressive and obsessive
      compulsive symptoms and their co-occurrence.
AB  - BACKGROUND AND OBJECTIVES: Depressive and obsessive-compulsive (OC) symptoms are
      frequently comorbid, and the combination of these may result in additional
      impairment compared to the difficulties of experiencing one of these symptom
      groups. Emotion regulation difficulties underlie many forms of psychopathology
      symptoms, and this study examined whether aspects of emotion regulation could
      differentiate clinical levels of depressive and OC symptoms, and their co
      occurrence. DESIGN AND METHOD: College students (N = 199; Mage = 19.47 years;
      59.8% female) were grouped based on the presence of clinical levels of OC and
      depressive symptoms. Using a multinomial logistic regression approach,
      differences in odds ratios for emotion regulation difficulties were examined.
      RESULTS: The co-occurring clinical-symptom group was differentiated from the
      single clinical-symptom groups on several aspects of emotion regulation. Impulse
      control difficulties and limited access to emotion regulation strategies
      differentiated clinical levels of depressive from OC symptoms. CONCLUSIONS: This
      study highlights the importance of conducting a nuanced emotion assessment to
      best inform prevention and treatment of depressive and OC symptoms, and their
      comorbidity.

PMID- 26315312
TI  - Endoscopic Transcanal Inlay Myringoplasty: Alternative Approach for Anterior
      Perforations.

PMID- 26315313
TI  - Partial Epiglottoplasty for Pharyngeal Dysphagia due to Cervical Spine Pathology.
AB  - OBJECTIVE: To examine the role of epiglottoplasty in patients with pharyngeal
      dysphagia due to pharyngeal crowding from cervical spine pathology and to assess
      swallowing outcomes following epiglottoplasty. STUDY DESIGN: Retrospective case
      series. SETTING: Academic tertiary care medical center. SUBJECTS AND METHODS:
      Dysphagia can occur in patients with cervical spine pathology because of
      hypopharyngeal crowding. Swallowing studies, such as modified barium swallow
      study and fiberoptic endoscopic evaluation of swallowing, may demonstrate a
      nonretroflexing epiglottis owing to cervical spine osteophytes or hardware, thus
      impeding pharyngeal bolus transit. We performed partial epiglottoplasties in a
      series of these patients. A retrospective review of swallowing outcomes was
      performed to assess the efficacy of this surgery in this patient population.
      RESULTS: Epiglottic dysfunction causing dysphagia due to cervical spine pathology
      was diagnosed by modified barium swallow study and/or fiberoptic endoscopic
      evaluation of swallowing in 12 patients. Findings included hypopharyngeal
      crowding because of cervical osteophytes (n = 8) or cervical hardware (n = 4)
      associated with absent epiglottic retroflexion and retained vallecular residue.
      Partial epiglottoplasty resulted in significant reduction of vallecular residue
      and a significant increase in functional swallow outcomes without an increase in
      swallow morbidity. CONCLUSION: There is a role for partial epiglottoplasty in
      patients with dysphagia attributed to hypopharyngeal crowding from cervical spine
      pathology. Surgery enables reduced vallecular residue and improved functional
      swallowing outcomes.

PMID- 26315314
TI  - More Than Capacity: Alternatives for Sexual Decision Making for Individuals With
      Dementia.
AB  - Sexual expression can be an important aspect of well being for older adults with
      dementia living in nursing homes. There is a tension in the nursing home,
      however, between ensuring autonomy of residents for sexual expression and
      protecting residents from harm. To alleviate this tension, nursing homes can
      conduct an assessment of residents' capacity for sexual consent. This article
      argues that although such assessments can be useful in the initial evaluation of
      capacity, this is a somewhat flawed approach to sexual decision making and a
      finding of incapacity should not necessarily preclude sexual expression. In
      instances where residents are found to lack capacity but continue to express
      interest in sexual expression, a committee approach can be utilized where
      residents, the nursing home, and family members can convene to advocate for
      residents' autonomy, dignity, and right to sexual expression while working to
      minimize harm. Such advocacy decisions can be based on substituted judgment, a
      best interest standard, or some combination of the two. Although committee
      decision making for sexual expression seems intrusive, it at least allows for
      continued discussion of the right to sexual freedom for residents in the face of
      significant counterbalancing forces. 

PMID- 26315315
TI  - Aging in Poland.
AB  - With 38 million residents, Poland has the eighth-largest population in Europe. A
      successful transition from communism to democracy, which began in 1989, has
      brought several significant changes to the country's economic development,
      demographic structure, quality of life, and public policies. As in the other
      European countries, Poland has been facing a rapid increase in the number of
      older adults. Currently, the population 65 and above is growing more rapidly than
      the total population and this discrepancy will have important consequences for
      the country's economy. As the population ages, there will be increased demands to
      improve Poland's health care and retirement systems. This article aims to provide
      a brief overview of the demographic trends in Poland as well a look at the
      country's major institutions of gerontology research. The article also describes
      key public policies concerning aging and how these may affect the well-being of
      Poland's older adults. 

PMID- 26315316
TI  - Dual Sensory Loss in Older Adults: A Systematic Review.
AB  - PURPOSE OF THE STUDY: Combined vision and hearing loss [dual sensory loss (DSL)]
      is commonly experienced by older adults. The literature on comorbidities and
      outcomes associated with DSL in older adults is limited and thus a systematic
      review was conducted to explore the existing research and identify gaps in the
      evidence base. DESIGN AND METHODS: A review was conducted in accordance with the
      Preferred Reporting Items for Systematic Reviews. Forty-two articles were
      selected for review. RESULTS: Although several studies evaluated DSL and its
      comorbidities and impacts, few fully met the criteria for good study design.
      Reviewed studies primarily investigated DSL and its comorbidities using cross
      sectional methods and varying methods of vision and hearing assessment. Many of
      the studies were large population studies that did not provide sufficient
      information to draw valid conclusions about the impact of DSL in older adults.
      IMPLICATIONS: Studies focusing specifically on sensory loss in older people
      across a broad age range are needed to inform clinical practice so that DSL and
      its impacts in older adults can be identified and managed, leading to improved
      quality of life for this population.

PMID- 26315317
TI  - Living With Ambiguity: A Metasynthesis of Qualitative Research on Mild Cognitive
      Impairment.
AB  - PURPOSE OF THE STUDY: Mild Cognitive Impairment (MCI) is a diagnosis proposed to
      describe an intermediate state between normal cognitive aging and dementia. MCI
      has been criticised for its conceptual fuzziness, its ambiguous relationship to
      dementia, and the tension it creates between medical and sociological
      understandings of "normal aging". DESIGN AND METHODS: We examined the published
      qualitative literature on experiences of being diagnosed and living with MCI
      using metasynthesis as the methodological framework. RESULTS: Two overarching
      conceptual themes were developed. The first, MCI and myself-in-time, showed that
      a diagnosis of MCI could profoundly affect a person's understanding of their
      place in the world. This impact appears to be mediated by multiple factors
      including a person's social support networks, which daily activities are
      affected, and subjective interpretations of the meaning of MCI. The second theme,
      Living with Ambiguity, describes the difficulties people experienced in making
      sense of their diagnosis. Uncertainty arose, in part, from lack of clarity and
      consistency in the information received by people with MCI, including whether
      they are even told MCI is the diagnosis. IMPLICATIONS: We conclude by suggesting
      an ethical tension is always at play when a MCI diagnosis is made. Specifically,
      earlier support and services afforded by a diagnosis may come at the expense of a
      person's anxiety about the future, with continued uncertainty about how his or
      her concerns and needs can be addressed.

PMID- 26315318
TI  - Optimization of Droplet Digital PCR from RNA and DNA extracts with direct
      comparison to RT-qPCR: Clinical implications for quantification of Oseltamivir
      resistant subpopulations.
AB  - The recent introduction of Droplet Digital PCR (ddPCR) has provided researchers
      with a tool that permits direct quantification of nucleic acids from a wide range
      of samples with increased precision and sensitivity versus RT-qPCR. The sample
      interdependence of RT-qPCR stemming from the measurement of Cq and DeltaCq values
      is eliminated with ddPCR which provides an independent measure of the absolute
      nucleic acid concentration for each sample without standard curves thereby
      reducing inter-well and inter-plate variability. Well-characterized RNA purified
      from H275-wild type (WT) and H275Y-point mutated (MUT) neuraminidase of influenza
      A (H1N1) pandemic 2009 virus was used to demonstrate a ddPCR optimization
      workflow to assure robust data for downstream analysis. The ddPCR reaction mix
      was also tested with RT-qPCR and gave excellent reaction efficiency (between 90%
      and 100%) with the optimized MUT/WT duplexed assay thus enabling the direct
      comparison of the two platforms from the same reaction mix and thermal cycling
      protocol. ddPCR gave a marked improvement in sensitivity (>30-fold) for mutation
      abundance using a mixture of purified MUT and WT RNA and increased precision (>10
      fold, p<0.05 for both inter- and intra-assay variability) versus RT-qPCR from
      patient samples to accurately identify residual mutant viral population during
      recovery. 

PMID- 26315319
TI  - Evaluation of two HIV antibody confirmatory assays: GeeniusTM HIV1/2 Confirmatory
      Assay and the recomLine HIV-1 & HIV-2 IgG Line Immunoassay.
AB  - The laboratory diagnosis of an HIV infection mainly depends on the detection of
      HIV-specific antibodies/HIV p24 antigen whereby different algorithms for the
      confirmation of reactive screening assays exist. The objective of the present
      study was to compare the performance of two supplemental HIV antibody
      confirmatory assays: the GeeniusTM HIV1/2 Confirmatory Assay and the recomLine
      HIV-1 & HIV-2 IgG Line Immunoassay. Therefore 279 serum samples previously
      analyzed for HIV during routine diagnostics at the Institute for Medical
      Virology, National Reference Center for Retroviruses, University Hospital
      Frankfurt, were analyzed retrospectively. 96.8% samples had concordant results in
      both HIV confirmatory assays, whereby the Geenius Assay showed a discrimination
      rate of 100% while two HIV-1 samples were not typeable with the recomLine Assay.
      Overall assay sensitivity was 100% in both assays and specificity was 99.0%
      (recomLine Assay) and 93.4% (Geenius Assay), respectively. The kappa-values for
      both assays indicated high agreement. Overall nine samples had discordant results
      from which four were from acutely EBV/CMV-infected patients and one from a
      patient with primary HIV-1 infection during seroconversion. In conclusion, both
      assays are well suited for the detection, confirmation and discrimination of HIV
      1- and -2-specific antibodies. 

PMID- 26315320
TI  - Qiliqiangxin Protects Against Cardiac Ischemia-Reperfusion Injury via Activation
      of the mTOR Pathway.
AB  - BACKGROUND/AIMS: Qiliqiangxin (QL) has been used for the treatment of chronic
      heart failure in China. Accumulating evidence suggests QL's cardio-protective
      effects on continuous myocardial ischemia. However, it is unclear whether QL has
      beneficial effects on cardiac ischemia-reperfusion (I/R) injury. METHODS: A mouse
      model of cardiac I/R was established by ligation of the left anterior descending
      coronary artery for 45 minutes followed by reperfusion. The mice were treated
      with QL for three days before surgery and continually after I/R.
      Triphenyltetrazolium chloride staining, echocardiography and Masson's trichrome
      staining were used to determine infarct size, cardiac function, and fibrosis,
      respectively. Expression levels of phospho-mTOR (Ser2448), mTOR, phospho-4EBP
      (Ser65), 4EBP, phospho-Akt (Ser473) and Akt were detected by Western blotting.
      RESULTS: At 1 day after I/R, QL treatment significantly reduced the infarct size
      of mice exposed to I/R. At 7 days after I/R, mortality was reduced in QL treated
      animals in comparison with the control group. In addition, QL treated mice showed
      increased left ventricular ejection fraction (LVEF) and left ventricular
      fractional shortening (LVFS) at 1 and 7 days after I/R. In agreement, Masson's
      trichrome staining demonstrated that interstitial fibrosis was less pronounced in
      QL treated mice compared with controls, suggesting that adverse left ventricular
      remodeling is attenuated in QL treated mice. Moreover, western blotting analysis
      demonstrated that QL activated the mTOR pathway, while mTOR inhibition via
      Rapamycin abolished the protective effects of QL against I/R injury. CONCLUSION:
      This study suggests that QL attenuates the progression of cardiac remodeling
      after I/R likely via mTOR activation. This represents a new application for QL in
      the prevention of I/R injury.

PMID- 26315322
TI  - Response to the Letter by Canbaz et al.

PMID- 26315323
TI  - Importance of the intraoperative appearance of preserved parathyroid glands after
      total thyroidectomy.
AB  - PURPOSE: Hypocalcemia after total thyroidectomy is a concern for every endocrine
      surgeon. We conducted this study to establish the value of the macroscopic
      appearance of preserved parathyroid glands after thyroidectomy in predicting post
      thyroidectomy hypocalcemia. METHODS: In 2009, 237 patients underwent total
      thyroidectomy at our hospital. The macroscopic appearance of the preserved
      parathyroid glands was recorded and the serum calcium and intact parathyroid
      hormone levels were measured postoperatively. RESULTS: Thirteen patients (5.5 %)
      had transient hypocalcemia and 1 patient (0.4 %) had permanent hypocalcemia. All
      of the hypocalcemia patients with more than one normal preserved parathyroid had
      asymptomatic transient hypocalcemia that did not require medication. The
      sensitivity, specificity, positive predictive value, and negative predictive
      value for hypocalcemia with at least 1 normal preserved parathyroid were 78.6,
      79.4, 19.3, and 98.3 %, respectively. CONCLUSION: The macroscopic appearance of
      preserved parathyroid glands and the number of well-preserved parathyroid glands
      after thyroidectomy proved effective in predicting post-thyroidectomy
      hypocalcemia.

PMID- 26315321
TI  - Brain health: the importance of recognizing cognitive impairment: an IAGG
      consensus conference.
AB  - Cognitive impairment creates significant challenges for patients, their families
      and friends, and clinicians who provide their health care. Early recognition
      allows for diagnosis and appropriate treatment, education, psychosocial support,
      and engagement in shared decision-making regarding life planning, health care,
      involvement in research, and financial matters. An IAGG-GARN consensus panel
      examined the importance of early recognition of impaired cognitive health. Their
      major conclusion was that case-finding by physicians and health professionals is
      an important step toward enhancing brain health for aging populations throughout
      the world. This conclusion is in keeping with the position of the United States'
      Centers for Medicare and Medicaid Services that reimburses for detection of
      cognitive impairment as part the of Medicare Annual Wellness Visit and with the
      international call for early detection of cognitive impairment as a patient's
      right. The panel agreed on the following specific findings: (1) validated
      screening tests are available that take 3 to 7 minutes to administer; (2) a
      combination of patient- and informant-based screens is the most appropriate
      approach for identifying early cognitive impairment; (3) early cognitive
      impairment may have treatable components; and (4) emerging data support a
      combination of medical and lifestyle interventions as a potential way to delay or
      reduce cognitive decline. 

PMID- 26315324
TI  - Feasibility of the liver-first approach for patients with initially unresectable
      and not optimally resectable synchronous colorectal liver metastases.
AB  - PURPOSE: To investigate the outcomes of patients with colorectal cancer and
      initially unresectable or not optimally resectable liver metastases, who were
      treated using the liver-first approach in the era of modern chemotherapy in
      Japan. METHODS: We analyzed and compared data retrospectively on patients with
      asymptomatic resectable colorectal cancer and initially unresectable or not
      optimally resectable liver metastases, who were treated either using the liver
      first approach (n = 12, LF group) or the primary-first approach (n = 13, PF
      group). RESULTS: Both groups of patients completed their therapeutic plan and
      there was no mortality. Postoperative morbidity rates after primary resection and
      hepatectomy, and post-hepatectomy liver failure rate were comparable between the
      groups (p = 1.00, p = 0.91, and p = 0.55, respectively). Recurrence rates, median
      recurrence-free survival since the last operation, and 3-year overall survival
      rates from diagnosis were also comparable between the LF and PF groups (58.3 vs.
      61.5 %, p = 0.87; 10.5 vs. 18.6 months, p = 0.57; and 87.5 vs. 82.5 %, p = 0.46,
      respectively). CONCLUSIONS: The liver-first approach may be an appropriate
      treatment sequence without adversely affecting perioperative or survival outcomes
      for selected patients.

PMID- 26315325
TI  - Genes encoding ten newly designated OXA-63 group class D beta-lactamases
      identified in strains of the pathogenic intestinal spirochaete Brachyspira
      pilosicoli.
AB  - The anaerobic spirochaete Brachyspira pilosicoli colonizes the large intestine of
      birds and mammals, including human beings, and may induce colitis and diarrhoea.
      B. pilosicoli has a recombinant population structure, and strains show extensive
      genomic rearrangements and different genome sizes. The resident chromosomal gene
      blaOXA-63 in B. pilosicoli encodes OXA-63, a narrow-spectrum group IV class D
      beta-lactamase. Genes encoding four OXA-63 variants have been described in B.
      pilosicoli, and the current study was designed to investigate the distribution
      and diversity of such genes and proteins in strains of B. pilosicoli. PCRs were
      used to amplify blaOXA-63 group genes from 118 B. pilosicoli strains from
      different host species and geographical origins. One primer set was targeted
      externally to the gene and two sets were designed to amplify internal components.
      A total of 16 strains (13.6%) showed no evidence of possessing blaOXA-63 group
      genes, 44 (37.3%) had a full gene, 27 (22.9%) apparently had a gene but it failed
      to amplify with external primers, and 29 (24.6%) had only one or other of the two
      internal components amplified. Based on translation of the nucleotide sequences,
      ten new variants of the beta-lactamase, designated OXA-470 through OXA-479, were
      identified amongst the 44 strains that had the full gene amplified. The 16
      strains lacking blaOXA-63 group genes had a region of 1674 bp missing around
      where the gene was expected to reside. Despite apparent genomic rearrangements
      occurring in B. pilosicoli, positive selection pressures for conservation of
      blaOXA-63 group genes and OXA proteins appear to have been exerted.

PMID- 26315326
TI  - Identifying an outcome measure to assess the impact of Mobility Dogs.
AB  - PURPOSE: Mobility Dogs(r) trains dogs to work with people with physical
      disabilities to increase independence, confidence, self-esteem and participation.
      Mobility Dogs(r) seeks to critically evaluate and improve its services as it
      grows. This study aimed to identify and implement a standardised outcome measure
      into practice at Mobility Dogs(r). METHOD: Based on the Consolidated Framework
      for Implementation Research and guided by a steering group of key stakeholders, a
      three-phase approach was developed to identify and assess an outcome measure. The
      steering group highlighted the organisation's specific needs, selected
      participation as the assessment domain and identified core utility requirements
      of the measure. A comprehensive review of evidence was undertaken to identify and
      rank potential measures according to the specified needs. RESULTS: Of the seven
      participation outcome measures that met inclusion criteria, the three highest
      ranked measures were critically evaluated by the steering group to determine
      suitability against the organisation's needs. The Impact on Participation and
      Autonomy (IPA) was selected for implementation into practice at Mobility Dogs(r).
      CONCLUSION: Use of the IPA is an important first step for Mobility Dogs(r) to
      test the benefits of trained service dogs. This process could be replicated by
      other service dog organisations to identify outcome measures to assess their own
      services. Implications for Rehabilitation Service dogs (such as Mobility Dogs(r)
      in New Zealand) assist people living with physical impairments by performing
      tasks, however there is limited evidence on outcomes. The process for selecting
      an appropriate outcome measure for Mobility Dogs(r) involving partnership between
      Mobility Dogs(r) personnel and academics was an effective way to steer the
      project by determining important properties of the measure, before a search of
      the literature was undertaken. While the IPA was selected as the most appropriate
      outcome measure for use at Mobility Dogs(r), it was the process that is valuable
      to replicate if other organisations wish to select an outcome measure for use in
      their own practice.

PMID- 26315327
TI  - Crime Victimisation and Subjective Well-Being: Panel Evidence From Australia.
AB  - This paper estimates the effect of physical violence and property crimes on
      subjective well-being in Australia. Our methodology improves on previous
      contributions by (i) controlling for the endogeneity of victimisation and (ii)
      analysing the heterogeneous effect of victimisation along the whole distribution
      of well-being. Using fixed effects panel estimation, we find that both types of
      crimes reduce reported well-being to a large extent, with physical violence
      exerting a larger average effect than property crimes. Furthermore, using
      recently developed panel data quantile regression model with fixed effects, we
      show that the negative effects of both crimes are highly heterogeneous, with a
      monotonic decrease over the distribution of subjective well-being. Copyright (c)
      2015 John Wiley & Sons, Ltd.

PMID- 26315328
TI  - Reply: To PMID 25989470.

PMID- 26315329
TI  - Genomic detection and characterization of a Korean isolate of Little cherry virus
      1 sampled from a peach tree.
AB  - A peach tree (Prunus persica) showing yellowing and mild mottle symptoms was
      analyzed using high-throughput RNA sequencing to determine the causal agent. A
      total of nine contigs similar to Little cherry virus 1 (LChV-1) were produced,
      and all the contigs showed nucleotide sequence identity (lower than 83 %) and
      query coverage (higher than 73 %) with LChV-1. The symptomatic peach sample was
      confirmed to be infected with LChV-1-like virus as a result of reverse
      transcription-polymerase chain reaction using primers designed based on sequences
      of the contigs. Occurrence of diseases caused by LChV-1 in Prunus species has
      been reported. Complete 16,931-nt genome of the peach virus composed of eight
      open reading frames was determined, and conserved domains including viral
      methyltransferase, viral helicase 1, RNA-dependent RNA polymerase (RdRp), heat
      shock protein 70 homologue (HSP70h), HSP90h and closterovirus coat protein (CP)
      were identified. Phylogenetic trees based on amino acid sequence alignments
      between the peach virus and members in the family Closteroviridae showed that the
      virus was most similar to LChV-1. Pairwise comparisons based on amino acid
      sequence alignments of three genes (RdRp, HSP70h and CP) between the peach virus
      and LChV-1 isolates showed the highest amino acid sequence identities, with 84.32
      % for RdRp, 85.48 % for HSP70h and 80.45 % for CP. These results indicate that
      this is the first report for the presence of LChV-1 in South Korea and may be one
      of the first reports of natural infection of peach by LChV-1. Although it is not
      clear if LChV-1 YD isolate was responsible for specific symptoms observed,
      detection and characterization of the peach tree-infecting LChV-1 in South Korea
      would be useful in terms of the epidemiology of LChV-1.

PMID- 26315330
TI  - Parrot bornavirus-2 and -4 RNA detected in wild bird samples in Japan are
      phylogenetically adjacent to those found in pet birds in Japan.
AB  - Bornaviruses (family Bornaviridae) are non-segmented negative-strand RNA viruses.
      Avian bornaviruses (ABVs), which are causative agents of proventricular
      dilatation disease, are a genetically diverse group with at least 15 genotypes,
      including parrot bornaviruses (PaBVs) and aquatic bird bornavirus 1(ABBV-1).
      Borna disease virus 1(BoDV-1), which infects mammals and causes neurological
      diseases, has also been reported to infect avian species, although the numbers of
      the cases have been markedly fewer than those of ABVs. In this study, we
      conducted genetic surveillance to detect ABVs (PaBV-1 to -5 and ABBV-1) and BoDV
      1 in wild birds in Japan. A total of 2078 fecal or cloacal swab samples were
      collected from wild birds in 2006, 2007, 2008, and 2011, in two regions of Japan.
      The results demonstrated the presence of PaBV-2 and -4 RNA, while no positive
      results for other PaBVs, ABBV-1, and BoDV-1 were obtained. PaBV-2 and -4 RNA were
      detected in 18 samples (0.9 %) of the genera Anas, Grus, Larus, Calidris,
      Haliaeetus, and Emberiza, in which either PaBV-2 RNA or PaBV-4 RNA, or both PaBV
      2 and -4 RNA were detected in 15 (0.7 %), 5 (0.2 %), and 2 (0.1 %) samples,
      respectively. The nucleotide sequences of PaBV-2 and -4 detected in these samples
      from wild birds are phylogenetically close to those found in samples from pet
      birds in Japan, with identities ranging from 99.8 to 100 % and from 98.2 to 99.4
      %, respectively. To the best of our knowledge, this is the first report on the
      detection of PaBV-2 and -4 RNA detected in samples from wild birds.

PMID- 26315331
TI  - Diabetic hepatosclerosis: another diabetes microvascular complication?
AB  - BACKGROUND: Liver disease in diabetes is common and is frequently the result of
      hepatic steatosis. Diabetic hepatosclerosis is a relatively recent description of
      sinusoidal fibrosis, without steatosis, observed in liver biopsies of people with
      diabetes presenting with cholestasis. Its association with other microvascular
      complications suggests it is a form of hepatic diabetic microangiopathy. CASE
      REPORT: We report the case of a 50-year-old woman with longstanding Type 1
      diabetes, complicated by nephropathy resulting in cadaveric renal transplant,
      retinopathy, gastroparesis and neuropathy with slowly healing ulceration to her
      right foot. She was noted to have deranged liver function tests: alanine
      aminotransferase, 162 IU/l; bilirubin, 44 IU/l; alkaline phosphatase, 5279 IU/l
      (isoenzymes; bone 1029 IU/l, liver 4250 IU/l); gamma-glutamyl transferase, 662
      IU/l. A non-invasive liver screen did not reveal the cause of the cholestasis. A
      liver biopsy demonstrated sinusoidal fibrosis without evidence of steatosis and
      thus a diagnosis of diabetic hepatosclerosis was made. Comparison with a biopsy
      performed 11 years previously at a different trust due to elevated alkaline
      phosphatase levels revealed slow progression of the sinusoidal fibrosis.
      DISCUSSION: This case describes the longest reported clinical course of diabetic
      hepatosclerosis, spanning 11 years, in which time the patient did not develop
      evidence of cirrhosis or portal hypertension. It is difficult to estimate the
      clinical relevance of this condition because little is known regarding its
      clinical course and effect on morbidity and mortality. Identified patients should
      undergo low-intensity, long-term follow-up to improve understanding of its
      clinical sequelae and relevance.

PMID- 26315332
TI  - Gap-balancing technique combined with patient-specific instrumentation in TKA.
AB  - INTRODUCTION: Combining patient-specific instrumentation (PSI) with a balancer
      device in total knee arthroplasty (TKA) to achieve functional femoral rotational
      alignment is a novel technique. The primary goal of this study was to introduce a
      new method to combine PSI with a gap-balancing technique and to determine the
      impact of the technique on rotation of the femoral component. MATERIALS AND
      METHODS: Twenty-five primary TKAs (15 women, 10 men) were prospectively studied.
      All TKAs involved PSI with an associated gap-balancing device. Front plane
      alignment was performed intraoperatively with the PSI, followed by rectangular,
      symmetrical extension and creation of a flexion gap using the balancer device to
      set the femoral rotation. RESULTS: Femoral component rotation was between 3
      degrees  internal and 6 degrees  external rotation versus the transepicondylar
      axis. There were no postoperative signs of patellofemoral dysfunction. In no
      cases was the resulting joint line displacement >3 mm. The mean elevation was 1.2
      +/- 0.9 mm (range 0-3). The leg axis was straight in all cases (+/-3 degrees ),
      at a mean of 1.6 degrees  +/- 1.0 degrees  varus (range 0 degrees -3 degrees 
      varus). CONCLUSIONS: PSI was with the gap-balancing technique was successfully
      used without affecting anatomical alignment. With the balancer device, PSI can be
      used more widely than techniques based solely on landmarks, as the soft-tissue
      tension can be taken into account, thus virtually eliminating flexion
      instabilities.

PMID- 26315333
TI  - Morphological Variations in the Transverse Venous Sinus Anatomy of Dogs and its
      Relationship to Skull Landmarks.
AB  - We characterized the anatomical morphology of the transverse venous sinus (TVS)
      of 69 canine adult cadavers belonging to three groups: brachycephalic (B),
      dolichocephalic (D) and mesaticephalic (M). In addition, we outlined its path
      over the skull using five classic human craniometric points (CPs): the asterion
      (ast), the bregma (b), the glabella (g), the stephanion (st) and the pterion
      (pt). The study aimed to establish anatomical differences in the TVS between
      groups and in the relationship between the TVS and skull. We found that TVS
      anatomy and its relationships to skull landmarks vary markedly between the
      groups, with similar anatomical arrangements in B and M. The TVS length can be
      ranked as M < B < D (with D being the biggest), whereas the width can be ranked
      as M < D < B (with B being the widest) with the right side being smaller than the
      left. In the B and M groups, the TVS assumes a craniocaudal trajectory that is
      closer to the lateral skull wall than in D, where the TVS presents a caudocranial
      direction. By documenting the morphological characteristics of the TVS, we can
      create a set of anatomical references allowing construction of a basic framework
      to greatly decrease the probability of TVS injury during neuronavigation
      procedures when supported by a good knowledge of the skull, brain anatomies and
      their relationships. 

PMID- 26315335
TI  - Corrigendum: Palladium-Catalyzed Three-Component Cascade Reaction: Facial Access
      to Densely Functionalized Indolizines.

PMID- 26315337
TI  - Biomolecular DNP-Supported NMR Spectroscopy using Site-Directed Spin Labeling.
AB  - Dynamic nuclear polarization (DNP) has been shown to greatly enhance
      spectroscopic sensitivity, creating novel opportunities for NMR studies on
      complex and large molecular assemblies in life and material sciences. In such
      applications, however, site-specificity and spectroscopic resolution become
      critical factors that are usually difficult to control by current DNP-based
      approaches. We have examined in detail the effect of directly attaching mono- or
      biradicals to induce local paramagnetic relaxation effects and, at the same time,
      to produce sizable DNP enhancements. Using a membrane-embedded ion channel as an
      example, we varied the degree of paramagnetic labeling and the location of the
      DNP probes. Our results show that the creation of local spin clusters can
      generate sizable DNP enhancements while preserving the intrinsic benefits of
      paramagnetic relaxation enhancement (PRE)-based NMR approaches. DNP using
      chemical labeling may hence provide an attractive route to introduce molecular
      specificity into DNP studies in life science applications and beyond. 

PMID- 26315340
TI  - Long-Term Followup of a Multicenter Cohort of 101 Patients With Eosinophilic
      Granulomatosis With Polyangiitis (Churg-Strauss).
AB  - OBJECTIVE: To assess the long-term outcome in eosinophilic granulomatosis with
      polyangiitis (Churg-Strauss) (EGPA). METHODS: A total of 101 patients fulfilling
      the American College of Rheumatology criteria for EGPA were included between 1990
      and 2011. Clinical features, antineutrophil cytoplasm autoantibodies (ANCAs), and
      Five-Factors Score (FFS) were assessed at diagnosis. Overall and cumulative
      survival rates, relapse-free survival, and sequelae were studied based on ANCA
      status and FFS. RESULTS: The rate of cardiomyopathy did not differ according to
      ANCA status. A total of 79.6% of patients achieved first remission, but 81.1%
      relapsed. ANCA-positive patients did not relapse more frequently but exhibited
      more severe disease with mononeuritis (P = 0.0004) and renal involvement (P =
      0.02). Being Italian was the only prognostic factor associated with a higher
      relapse-free survival (P = 0.01), thanks to a longer maintenance of
      immunosuppressive drugs, suggesting the need for prolonged low-dose
      corticosteroids. Overall, survival reached 93.1% after a median followup of 6
      years. No factor was associated with mortality, but patients over age 65 years
      with cardiomyopathy or ANCA positivity had more serious outcomes. Sequelae
      affected 83.2% of patients. Ear, nose, and throat (ENT) involvement was a
      protective factor for renal (P = 0.04) and cardiac (P = 0.03) morbidity. ANCA
      positivity was correlated with chronic kidney disease (P = 0.03) and chronic
      neurologic disability (P = 0.02). CONCLUSION: The actual challenges of EGPA
      management concern morbidity prevention and quality of life improvement. Long
      term corticosteroid treatment appears to reduce relapse risk. ENT involvement is
      associated with less renal and cardiac morbidity. ANCA positivity predicts renal
      and neurologic damage.

PMID- 26315341
TI  - A novel viral thymidylate kinase with dual kinase activity.
AB  - Nucleotide phosphorylation is a key step in DNA replication and viral infections,
      since suitable levels of nucleotide triphosphates pool are required for this
      process. Deoxythymidine monophosphate (dTMP) is produced either by de novo or
      salvage pathways, which is further phosphorylated to deoxythymidine triphosphate
      (dTTP). Thymidyne monophosphate kinase (TMK) is the enzyme in the junction of
      both pathways, which phosphorylates dTMP to yield deoxythymidine diphosphate
      (dTDP) using adenosine triphosphate (ATP) as a phosphate donor. White spot
      syndrome virus (WSSV) genome contains an open reading frame (ORF454) that encodes
      a thymidine kinase and TMK domains in a single polypeptide. We overexpressed the
      TMK ORF454 domain (TMKwssv) and its specific activity was measured with dTMP and
      dTDP as phosphate acceptors. We found that TMKwssv can phosphorylate dTMP to
      yield dTDP and also is able to use dTDP as a substrate to produce dTTP. Kinetic
      parameters K M and k cat were calculated for dTMP (110 MUM, 3.6 s(-1)), dTDP (251
      MUM, 0.9 s(-1)) and ATP (92 MUM, 3.2 s(-1)) substrates, and TMKwssv showed a
      sequential ordered bi-bi reaction mechanism. The binding constants K d for dTMP
      (1.9 MUM) and dTDP (10 MUM) to TMKwssv were determined by Isothermal Titration
      Calorimetry. The affinity of the nucleotidic analog stavudine monophosphate was
      in the same order of magnitude (K d 3.6 MUM) to the canonical substrate dTMP.
      These results suggest that nucleotide analogues such as stavudine could be a
      suitable antiviral strategy for the WSSV-associated disease.

PMID- 26315342
TI  - Oxidative stress-induced overexpression of miR-25: the mechanism underlying the
      degeneration of melanocytes in vitiligo.
AB  - Oxidative stress has a critical role in the pathogenesis of vitiligo. However,
      the specific molecular mechanism involved in oxidative stress-induced melanocyte
      death is not well characterized. Given the powerful role of microRNAs (miRNAs) in
      the regulation of cell survival as well as the fact that the generation of miRNAs
      can be affected by oxidative stress, we hypothesized that miRNAs may participate
      in vitiligo pathogenesis by modulating the expression of vital genes in
      melanocytes. In the present study, we initially found that miR-25 was increased
      in both serum and lesion samples from vitiligo patients, and its serum level was
      correlated with the activity of vitiligo. Moreover, restoration of miR-25
      promoted the H2O2-induced melanocyte destruction and led to the dysfunction of
      melanocytes. Further experiments proved that MITF, a master regulator in
      melanocyte survival and function, accounted for the miR-25-caused damaging impact
      on melanocytes. Notably, other than the direct role on melanocytes, we observed
      that miR-25 inhibited the production and secretion of SCF and bFGF from
      keratinocytes, thus impairing their paracrine protective effect on the survival
      of melanocytes under oxidative stress. At last, we verified that oxidative stress
      could induce the overexpression of miR-25 in both melanocytes and keratinocytes
      possibly by demethylating the promoter region of miR-25. Taken together, our
      study demonstrates that oxidative stress-induced overexpression of miR-25 in
      vitiligo has a crucial role in promoting the degeneration of melanocytes by not
      only suppressing MITF in melanocytes but also impairing the paracrine protective
      effect of keratinocytes. Therefore, it is worthy to investigate the possibility
      of miR-25 as a potential drug target for anti-oxidative therapy in vitiligo. 

PMID- 26315344
TI  - Polarization Rotation in Ferroelectric Tricolor PbTiO3/SrTiO3/PbZr0.2Ti0.8O3
      Superlattices.
AB  - In ferroelectric thin films, controlling the orientation of the polarization is a
      key element to controlling their physical properties. We use laboratory and
      synchrotron X-ray diffraction to investigate ferroelectric bicolor
      PbTiO3/PbZr0.2Ti0.8O3 and tricolor PbTiO3/SrTiO3/PbZr0.2Ti0.8O3 superlattices and
      to study the role of the SrTiO3 layers on the domain structure. In the tricolor
      superlattices, we demonstrate the existence of 180 degrees  ferroelectric stripe
      nanodomains, induced by the depolarization field produced by the SrTiO3 layers.
      Each ultrathin SrTiO3 layer modifies the electrostatic boundary conditions
      between the ferroelectric layers compared to the corresponding bicolor
      structures, leading to the suppression of the a/c polydomain states. Combined
      with the electrostatic effect, the tensile strain induced by PbZr0.2Ti0.8O3 in
      the PbTiO3 layers leads to polarization rotation in the system as evidenced by
      grazing incidence X-ray measurements. This polarization rotation is associated
      with the monoclinic Mc phase as revealed by the splitting of the (HHL) and (H0L)
      reciprocal lattice points. This work demonstrates that the tricolor
      paraelectric/ferroelectric superlattices constitute a tunable system to
      investigate the concomitant effects of strains and depolarizing fields. Our
      studies provide a pathway to stabilize a monoclinic symmetry in ferroelectric
      layers, which is of particular interest for the enhancement of the piezoelectric
      properties. 

PMID- 26315343
TI  - Eating Disorders and Problematic Eating Behaviours Before and After Bariatric
      Surgery: Characterization, Assessment and Association with Treatment Outcomes.
AB  - Accumulating evidence suggests that bariatric surgery candidates are likely to
      present with eating disorders (EDs) and/or problematic eating behaviours (EBs),
      and research suggests that these problems may persist or develop after bariatric
      surgery. While there is growing evidence indicating that EDs and EBs may impact
      bariatric surgery outcomes, the definitions and assessment methods used lack
      consensus, and findings have been mixed. The aims of this paper were (1) to
      summarize the existing literature on pre-operative and post-operative EDs and
      problematic EBs; (2) to discuss the terms, definitions and assessment measures
      used across studies; and (3) to consider the extent to which the presence of
      these problems impact surgery outcomes. We highlight the importance of
      investigators utilizing consistent definitions and assessment methodologies
      across studies.

PMID- 26315345
TI  - The involvement of aquaporin 1 in the hepatopulmonary syndrome rat serum-induced
      migration of pulmonary arterial smooth muscle cells via the p38-MAPK pathway.
AB  - Hepatopulmonary syndrome (HPS) is characterized by arterial oxygenation defects
      induced by intrapulmonary vascular dilation (IPVD). Pulmonary vascular remodeling
      (PVR) is an important pathological feature of IPVD; however, the details
      regarding the underlying mechanisms of this process remain undefined. Recent
      studies have determined that the abnormal migration of pulmonary arterial smooth
      muscle cells (PASMCs) plays a role in the pathogenesis of the PVR associated with
      HPS. Additionally, aquaporin 1 (AQP1) not only functions as a water channel
      molecule but also promotes cell migration by facilitating water transport in the
      lamellipodia of migrating cells. Common bile duct ligation (CBDL) rat is a well
      accepted HPS model; we determined that the immunoperoxidase labeling of AQP1 was
      enhanced in the media of the pulmonary vessels in CBDL rats. HPS rat serum
      mediated the overexpression of AQP1 in PASMCs, and also upregulated PASMC
      migration. Small interfering RNAs (siRNAs) that targeted rat AQP1 caused
      significant downregulation of AQP1, which resulted in decreased PASMC migration.
      Furthermore, the inhibition of the p38-MAPK pathway abolished AQP1-dependent
      PASMC migration. In conclusion, this study demonstrated that AQP1 enhanced PASMC
      migration via the p38-MAPK pathway in rat with HPS and may represent a potential
      therapeutic strategy in the setting of pulmonary vascular remodeling associated
      with HPS. 

PMID- 26315346
TI  - Subtrochanteric femoral fractures treated with the Long Gamma3(r) nail: A
      historical control case study versus Long trochanteric Gamma nail(r).
AB  - BACKGROUND: Gamma nail was developed for the treatment of subtrochanteric hip
      fractures. Despite its advantages over extramedullary devices, gamma nail has
      been historically related to significant complications (implant breakage, femoral
      fractures at the tip of the nail). There is limited data to determine if the rate
      of these complications was minimized by using a new design of the gamma nail.
      Therefore we performed a case control study between the long gamma3 nail (LG3N)
      and the long trochanteric gamma nail (LTGN) to assess if: (1) the complication
      rate in the treatment of subtrochanteric fractures using the LG3N was lower than
      the one using the LTGN; (2) the reoperation rate was lower after using the LG3N.
      HYPOTHESIS: The complication rate after fixation of subtrochanteric fracture of
      the femur is lower with LG3N than with the LTGN. PATIENTS AND METHODS: This study
      prospectively recorded the intra- and postoperative complications of 75 patients
      with subtrochanteric fractures treated with the LG3N and compared them with those
      of a historical cohort of 83 patients treated with the LTGN. The two groups were
      matched regarding age, gender and fracture type. Patients with open,
      pathological, or impending fractures were excluded. RESULTS: Intraoperative
      complications in the LG3N group were lower (4 cases, 5.3%) compared with those in
      the LTGN group (9 cases, 10.8%; P=0.04). The major intraoperative complication
      encountered with the use of LTGN was fracture of the femur in 3 cases. We
      encountered in total 9 postoperative complications in LG3N (12%) and 20 in group
      LTGN (24%). The most frequent complication in both groups was the cut out of the
      lag screw (3 cases in LG3N and 7 cases in LTGN group). The overall reoperation
      rate was higher in LTGN group (20.4% vs 10.6%; P=0.03). CONCLUSION: As a result
      of the improvement of its mechanical characteristics, LG3N has proved a safe and
      efficient implant for the treatment of subtochanteric fractures. The new design
      seems superior to previous generation, giving promising outcomes, reduced
      mechanical complication rates, and reduced reoperation rate. LEVEL OF EVIDENCE:
      Level III - case controlled study.

PMID- 26315347
TI  - Clinical application of radial magnetic resonance imaging for evaluation of
      rotator cuff tear.
AB  - BACKGROUND: Magnetic resonance imaging is useful for evaluating the rotator cuff,
      but some tendinous insertions cannot be assessed using oblique sagittal, oblique
      coronal, and axial magnetic resonance (MR) images because of the presence of the
      partial volume effect. HYPOTHESIS: The purpose of this study was to determine
      whether radial-slice MR images could reveal normal rotator cuff insertions and
      rotator cuff tears more clearly than conventional MR images. PATIENTS AND
      METHODS: The study included 18 subjects with normal rotator cuffs and 30 with
      rotator cuff tears. MR images of rotator cuff insertions sliced into radial,
      oblique coronal, and axial sections were obtained. The extent to which normal
      rotator cuff insertions and rotator cuff tears were visualized in each of the
      three MR images was evaluated. RESULTS: The top to posterior portions of the
      rotator cuff insertions from 0 degrees  to 120 degrees  could be visualized in
      the radial MR images. In comparison, the posterior portions of the rotator cuff
      insertions could not be visualized around 45 degrees  in both the oblique coronal
      and axial MR images. DISCUSSION: These findings demonstrate that radial MR images
      are superior to the oblique coronal and axial MR images regarding their ability
      to accurately visualize rotator cuff insertions. Radial MR images also revealed
      greater detail around 45 degrees  in the posterior area of the rotator cuff tears
      than the oblique coronal and axial MR images. Radial MR images are particularly
      useful for visualizing clinically important posterosuperior rotator cuff tears.
      LEVEL OF EVIDENCE: Level III - Diagnostic study.

PMID- 26315348
TI  - Does arthrodesis of the first metatarsophalangeal joint correct the
      intermetatarsal M1M2 angle? Analysis of a continuous series of 208 arthrodeses
      fixed with plates.
AB  - INTRODUCTION: First-ray metatarsophalangeal arthrodesis is a classic surgical
      procedure in the treatment of severe hallux valgus, hallux rigidus, revision
      surgery, and inflammatory arthritis. The objective of this study was to verify if
      metatarsophalangeal plate arthrodesis could correct the M1M2 intermetatarsal
      angle. MATERIAL AND METHODS: This prospective and continuous series (June 2007 to
      March 2011) included 208 patients (48% severe and/or arthritic hallux valgus, 18%
      hallux rigidus, 16% rheumatoid forefoot, 13% surgical revision of the first ray,
      5% hallux varus), with a mean age of 62.4+/-9.9 years (range, 19-87 years). All
      the patients were operated on by a senior surgeon with the same technique:
      spherical avivement of the joint surfaces using reamers, osteosynthesis with an
      anatomic plate (Fyxis-BiotechTM) in Ti.6Al.4 V alloy prebent to 5 degrees  with a
      phalangeal arm to receive an oblique metatarsophalangeal screw in compression, in
      addition to four 2.7-mm nonlocking dorsal screws. The full-scale preoperative and
      intraoperative angle measurements were taken on AP and lateral X-rays of the
      weightbearing foot, as related to the etiology and the severity of the
      preoperative metatarsus varus (M1M2<15 degrees , M1M2 15-19 degrees , M1M2>=20
      degrees ). The statistical analysis was done using the StatView software.
      RESULTS: The mean follow-up was 18.6+/-12.4 months (range, 2-76 months). Nearly
      all of the arthrodesis patients (97%) achieved bone union, and 5% of the plates
      were removed. The M1P1 angle decreased from 33.8+/-19.7 degrees  (range, -45
      degrees  to -67 degrees ) preoperatively to 13.3+/-5.3 degrees  (range, 0-32
      degrees ) at the last follow-up, and the M1M2 angle from 14.2+/-5.4 degrees
      (range, 0-26 degrees ) to 6.5+/-2.3 degrees  (range, 0-12 degrees ). The
      preoperative M1M2 angle was <15 degrees  in 97 patients, 15-19 degrees  for 78
      patients, and >=20 degrees  for the 33 others; at the last follow-up it was 5.8+/
      2.1 degrees  (range, 0-10 degrees ), 6.7+/-2.2 degrees  (0-10 degrees ), and
      8.1+/-2.4 degrees  (3-12 degrees ), respectively. No correction of the metatarsus
      varus was demonstrated in relation to etiology. The M1M2 angle was >10 degrees 
      in only two patients (one case of rheumatoid arthritis and one case of severe
      hallux valgus): 0.9%. DISCUSSION: These results show that isolated
      metatarsophalangeal arthrodesis of the first ray can correct metatarsus varus
      even in substantial deformations in any etiology. LEVEL OF PROOF: Level II cohort
      study.

PMID- 26315349
TI  - Do Children See in Black and White? Children's and Adults' Categorizations of
      Multiracial Individuals.
AB  - Categorizations of multiracial individuals provide insight into the development
      of racial concepts. Children's (4-13 years) and adults', both White (Study 1) and
      Black (Study 2; N = 387), categorizations of multiracial individuals were
      examined. White children (unlike Black children) more often categorized
      multiracial individuals as Black than as White in the absence of parentage
      information. White and Black adults (unlike children) more often categorized
      multiracial individuals as Black than as White, even when knowing the
      individuals' parentage. Children's rates of in-group contact predicted their
      categorizations. These data suggest that a tendency to categorize multiracial
      individuals as Black relative to White emerges early in development and results
      from perceptual biases in White children but ideological motives in White and
      Black adults.

PMID- 26315350
TI  - Effect of transportation and pre-slaughter water shower spray with resting on AMP
      activated protein kinase, glycolysis and meat quality of broilers during summer.
AB  - The aim of this study was to determine the effects of pre-slaughter transport
      during summer and subsequent water shower spray on stress, postmortem glycolysis,
      energy metabolism and adenosine monophosphate-activated protein kinase (AMPK) in
      Pectoralis major (PM) muscle of broilers. Results indicated that transport during
      high ambient temperature induced the release of plasma corticosterone, which
      significantly affected stress conditions. Moreover, we found a lower energy
      status in the early postmortem period compared to the control group. AMPK was
      activated in this situation, following by the rapid glycolysis and accumulation
      of lactic acid, leading to a high incidence of pale, soft, exudative (PSE)-like
      meat. Water shower spray with resting after transport relieved the stress
      situation, recovered energy homeostasis and lessened the deterioration of meat
      quality. As a key molecular target for the control of energy status, AMPK has a
      similar potential in regulating postmortem muscle glycolysis of broilers as in
      mammals. 

PMID- 26315351
TI  - A Review of Propensity-Score Methods and Their Use in Cardiovascular Research.
AB  - Observational studies using propensity-score methods have been increasing in the
      cardiovascular literature because randomized controlled trials are not always
      feasible or ethical. However, propensity-score methods can be confusing, and the
      general audience may not fully understand the importance of this technique. The
      objectives of this review are to describe (1) the fundamentals of propensity
      score methods, (2) the techniques to assess for propensity-score model adequacy,
      (3) the 4 major methods for using the propensity score (matching, stratification,
      covariate adjustment, and inverse probability of treatment weighting [IPTW])
      using examples from previously published cardiovascular studies, and (4) the
      strengths and weaknesses of these 4 techniques. Our review suggests that matching
      or IPTW using the propensity score have shown to be most effective in reducing
      bias of the treatment effect. 

PMID- 26315352
TI  - Assessment of the electrochemical effects of pulsed electric fields in a
      biological cell suspension.
AB  - Electroporation of cells is successfully used in biology, biotechnology and
      medicine. Practical problems still arise in the electroporation of cells in
      suspension. For example, the determination of cell electroporation is still a
      demanding and time-consuming task. Electric pulses also cause contamination of
      the solution by the metal released from the electrodes and create local
      enhancements of the electric field, leading to the occurrence of electrochemical
      reactions at the electrode/electrolyte interface. In our study, we investigated
      the possibility of assessing modifications to the cell environment caused by
      pulsed electric fields using electrochemical impedance spectroscopy. We designed
      an experimental protocol to elucidate the mechanism by which a pulsed electric
      field affects the electrode state in relation to different electrolyte
      conductivities at the interface. The results show that a pulsed electric field
      affects electrodes and its degree depends on the electrolyte conductivity.
      Evolution of the electrochemical reaction rate depends on the initial free
      charges and those generated by the pulsed electric field. In the presence of
      biological cells, the initial free charges in the medium are reduced. The
      electrical current path at low frequency is longer, i.e., conductivity is
      decreased, even in the presence of increased permeability of the cell membrane
      created by the pulsed electric field. 

PMID- 26315353
TI  - Tumor suppressor functions of BNIP3 and mitophagy.
AB  - There is a growing realization that tumor cells rely on healthy mitochondria to
      promote their growth under changing microenvironmental stresses and do so by
      dynamically modulating both their mitochondrial mass and state of mitochondrial
      fusion. Our recent work adds to this appreciation by showing that the mitophagy
      receptor BNIP3 functions as a tumor suppressor in mammary tumorigenesis and also
      as a prognostic indicator of progression to metastasis in certain sub-types of
      human breast cancer. 

PMID- 26315355
TI  - BRIP1 as an ovarian cancer susceptibility gene: ready for the clinic?

PMID- 26315356
TI  - Calcific uraemic arteriolopathy.
AB  - A 37-year-old African-American woman with end-stage renal disease presumed to be
      secondary to diabetes mellitus type 2, on daily peritoneal dialysis, was admitted
      for a painful left lower extremity lesion. Examination revealed a large, dusky,
      tender region over the left lateral thigh. She was on warfarin for mechanical
      heart valves. Despite discontinuation of warfarin and placement on heparin, the
      lesion progressed to extend to the medial left thigh and medial and lateral right
      thigh. CT scan demonstrated arteriolar medial calcification and vascular
      calcification of the small subcutaneous vessels, without evidence of abscess or
      haematoma. The patient declined punch biopsy. Given the known risk factors of
      high calcium-phosphate and radiological findings, a diagnosis of calcific uraemic
      arteriolopathy was made. Phosphate-binder therapy was optimised. She was
      transitioned to daily haemodialysis, and sodium thiosulfate was initiated. Skin
      lesions demonstrated improvement at her 5 weeks posthospitalisation follow-up. 

PMID- 26315357
TI  - Isolated brachiocephalic artery dissection presenting as acute stroke.
AB  - Isolated brachiocephalic artery dissection is an extremely rare condition. Its
      presentation as an acute stroke can pose a significant diagnostic challenge in
      patients because of its rarity. We present a case of isolated spontaneous
      brachiocephalic artery dissection presenting as acute cerebrovascular accident.
      This case also illustrates the treatment dilemma brachiocephalic artery
      dissection can present, whether to choose antithrombotic/anticoagulation therapy
      and/or surgery, and also the dilemma in blood pressure management. 

PMID- 26315354
TI  - Germline Mutations in the BRIP1, BARD1, PALB2, and NBN Genes in Women With
      Ovarian Cancer.
AB  - BACKGROUND: Epithelial ovarian cancer (EOC) is the most lethal gynecological
      malignancy, responsible for 13 000 deaths per year in the United States. Risk
      prediction based on identifying germline mutations in ovarian cancer
      susceptibility genes could have a clinically significant impact on reducing
      disease mortality. METHODS: Next generation sequencing was used to identify
      germline mutations in the coding regions of four candidate susceptibility genes
      BRIP1, BARD1, PALB2 and NBN-in 3236 invasive EOC case patients and 3431 control
      patients of European origin, and in 2000 unaffected high-risk women from a
      clinical screening trial of ovarian cancer (UKFOCSS). For each gene, we estimated
      the prevalence and EOC risks and evaluated associations between germline variant
      status and clinical and epidemiological risk factor information. All statistical
      tests were two-sided. RESULTS: We found an increased frequency of deleterious
      mutations in BRIP1 in case patients (0.9%) and in the UKFOCSS participants (0.6%)
      compared with control patients (0.09%) (P = 1 x 10(-4) and 8 x 10(-4),
      respectively), but no differences for BARD1 (P = .39), NBN1 ( P = .61), or PALB2
      (P = .08). There was also a difference in the frequency of rare missense variants
      in BRIP1 between case patients and control patients (P = 5.5 x 10(-4)). The
      relative risks associated with BRIP1 mutations were 11.22 for invasive EOC (95%
      confidence interval [CI] = 3.22 to 34.10, P = 1 x 10(-4)) and 14.09 for high
      grade serous disease (95% CI = 4.04 to 45.02, P = 2 x 10(-5)). Segregation
      analysis in families estimated the average relative risks in BRIP1 mutation
      carriers compared with the general population to be 3.41 (95% CI = 2.12 to 5.54,
      P = 7*10(-7)). CONCLUSIONS: Deleterious germline mutations in BRIP1 are
      associated with a moderate increase in EOC risk. These data have clinical
      implications for risk prediction and prevention approaches for ovarian cancer and
      emphasize the critical need for risk estimates based on very large sample sizes
      before genes of moderate penetrance have clinical utility in cancer prevention.

PMID- 26315358
TI  - A case of atypical Bartonella henselae infection in a patient with methimazole
      induced agranulocytosis.
AB  - Antithyroid medications such as methimazole and propylthiouracil are commonly
      used to treat hyperthyroid disorders. Thionamide-induced agranulocytosis is a
      rare but life-threatening potential side effect of these medicines. In addition
      to routine monitoring of blood counts, healthcare workers caring for patients on
      such medication need to be mindful of atypical presentations of acute
      agranulocytosis throughout the treatment course. The manifestations of underlying
      infectious aetiologies can be mistaken for more common illness and result in
      delayed diagnosis. We present a case of a 41-year-old woman receiving methimazole
      for Grave's disease, who presented to outpatient care with high fever,
      pharyngitis, lymphadenopathy and jaundice. After failing to respond to empiric
      antibiotics, a diagnosis of neutropenia was made and the patient was admitted for
      inpatient care with eventual recovery following a course of granulocyte colony
      stimulating factor. A diagnosis of atypical Bartonella henselae was eventually
      made and treated appropriately. The patient was later discharged and underwent
      radioactive iodine ablation. 

PMID- 26315359
TI  - Tamoxifen-associated portal vein thrombosis causing severe oesophageal variceal
      bleeding.
AB  - A 46-year-old woman with medical history of breast cancer on tamoxifen presented
      with syncope. On arrival to the hospital, the patient developed massive
      haematemesis and a subsequent esophagogastroduodenoscopy revealed oesophageal
      varices without any known history of liver disease. Further evaluation identified
      portal vein thrombosis probably caused by tamoxifen use. 

PMID- 26315360
TI  - Retinal artery vasculitis secondary to administration of influenza vaccine.
AB  - There are many differential diagnoses in investigating patients who present with
      retinal vasculitis, and the laboratory investigations used to investigate this
      have low-to-moderate sensitivity and/or specificity. Diagnoses include conditions
      such as tuberculosis or sarcoidosis, which may require long courses of
      antibiotics or immunosuppression. Influenza vaccination has been recognised as a
      cause of vasculitis for decades, although a purely ocular presentation is rare.
      We present a case of a 78-year-old Caucasian woman presenting with a single
      vessel arterial vasculitis of the right eye 8 weeks following influenza
      vaccination at her local general practitioner practice. We encourage
      ophthalmologists, rheumatologists and uveitis specialists to consider influenza
      vaccine as a cause of ocular vasculitis if the vaccine has been recently
      administered.

PMID- 26315361
TI  - Central retinal vein occlusion with cillioretinal artery occlusion in
      hyperhomocysteinemia.

PMID- 26315362
TI  - Simultaneous quantitation of two diastereoisomers of lobaplatin in rat plasma by
      supercritical fluid chromatography with tandem mass spectrometry and its
      application to a pharmacokinetic study.
AB  - Lobaplatin, consisting of two diastereoisomers, is a third-generation platinum
      antineoplastic agent that has shown encouraging anticancer activity in a variety
      of tumor types. To investigate any stereospecificity in the pharmacokinetics of
      lobaplatin, a novel, simple, rapid and sensitive supercritical fluid
      chromatography with tandem mass spectrometry method was developed for the
      simultaneous quantitation of lobaplatin diastereoisomers in rat plasma. After a
      simple protein precipitation with methanol, the analytes and dexpantoprazole
      (internal standard) were chromatographed on an Acquity UPC(2) system with a
      Chiralcel OZ-RH column using a mobile phase consisting of carbon dioxide and
      methanol (65:35, v/v) at 40 degrees C over 6 min. The assay was linear over a
      concentration range of 25-15,000 ng/mL for both diastereoisomers using 100 MUL of
      rat plasma for sample preparation. The lower limit of quantification was 25 ng/mL
      for both compounds, which was sufficient to detect the diastereoisomers in the
      incurred samples within this study. Intra- and inter-day precisions were below
      11.8% and the accuracies were below 4.5%. The validated method was successfully
      applied to a pharmacokinetic study after an intravenous administration of 7.6
      mg/kg lobaplatin to rats. There was no apparent stereospecificity in the
      pharmacokinetics between the two diastereoisomers of lobaplatin.

PMID- 26315363
TI  - Sphingosinicella cucumeris sp. nov., isolated from soil of a cucumber garden.
AB  - A novel bacterial strain, THG-sc1(T), was isolated from a soil sample of a
      cucumber garden and was characterised by using a polyphasic approach. Cells were
      observed to be Gram-stain negative, non-motile and rod-shaped. The strain was
      found to be aerobic, catalase and oxidase positive, esculin and starch negative,
      and to have an optimum growth temperature and pH of 28  degrees C and 7.5,
      respectively. On the basis of 16S rRNA gene sequence analysis, strain THG-sc1(T)
      was found to belong to the genus Sphingosinicella and to be closely related to
      Sphingosinicella vermicomposti KCTC 22446(T), followed by Sphingosinicella
      xenopeptidilytica DSM 17130(T) and Sphingosinicella microcystinivorans KCTC
      12019(T). The DNA G+C content was determined to be 60.8 mol% and the predominant
      respiratory quinone was identified as ubiquinone-10. The major polyamine was
      found to be sym-homospermidine. The major polar lipids were identified as
      sphingoglycolipid, phosphatidylethanolamine, phosphatidylglycerol and an
      unidentified phospholipid. The major fatty acids were identified as
      C(18:1)omega7c, C(16:0) and summed feature 3 (C(16:1)omega7c and/or iso-C(15:0) 2
      OH, as defined by MIDI). The results of the genotypic analysis, in combination
      with chemotaxonomic and physiological data, demonstrated that strain THG-sc1(T)
      represents a novel species within the genus Sphingosinicella, for which the name
      Sphingosinicella cucumeris is proposed. The type strain is THG-sc1(T) (=KACC
      18279(T) = CCTCC AB 2015120(T)).

PMID- 26315364
TI  - Arguments for choosing extracorporeal shockwave lithotripsy for removal of
      urinary tract stones.
AB  - At a time when there is an almost unlimited enthusiasm and preference among
      urologists for endoscopic stone removal, we have found it essential to meet some
      of the frequently presented arguments on why extracorporeal shockwave lithotripsy
      (SWL) should not be used. We have based our considerations in this brief article
      on our 30-35 years' experience with the non-invasive or least invasive technique
      that SWL represents. Stone disintegration, requirement of repeated treatment
      sessions, the concern of residual fragments, complications and economic aspects
      are some points that are discussed.

PMID- 26315365
TI  - 1.0 T open-configuration magnetic resonance-guided microwave ablation of pig
      livers in real time.
AB  - The current fastest frame rate of each single image slice in MR-guided ablation
      is 1.3 seconds, which means delayed imaging for human at an average reaction
      time: 0.33 seconds. The delayed imaging greatly limits the accuracy of puncture
      and ablation, and results in puncture injury or incomplete ablation. To overcome
      delayed imaging and obtain real-time imaging, the study was performed using a 1.0
      T whole-body open configuration MR scanner in the livers of 10 Wuzhishan pigs. A
      respiratory-triggered liver matrix array was explored to guide and monitor
      microwave ablation in real-time. We successfully performed the entire ablation
      procedure under MR real-time guidance at 0.202 s, the fastest frame rate for each
      single image slice. The puncture time ranged from 23 min to 3 min. For the pigs,
      the mean puncture time was shorted to 4.75 minutes and the mean ablation time was
      11.25 minutes at power 70 W. The mean length and widths were 4.62 +/- 0.24 cm and
      2.64 +/- 0.13 cm, respectively. No complications or ablation related deaths
      during or after ablation were observed. In the current study, MR is able to guide
      microwave ablation like ultrasound in real-time guidance showing great potential
      for the treatment of liver tumors. 

PMID- 26315366
TI  - Information processing in patients in vegetative and minimally conscious states.
AB  - OBJECTIVE: Evaluation of a short two-tone oddball paradigm to discriminate
      between the vegetative state (VS) and minimal consciousness state (MCS) in a
      sample of patients with severe disorders of consciousness (DOC). METHOD: EEG was
      recorded from 45 DOC patients and 14 healthy participants while listening to an
      auditory oddball paradigm presented in a passive - just listen - and an active -
      count the odd tones - condition. In patients, the experiment was repeated after a
      minimum of one week. RESULTS: Prevalence of the P300 was higher in healthy
      participants (71%) than in patients, but did not discriminate between VS (T1:
      ~10%; T2: ~11%) and MCS (T1: ~13%; T2: 25%) patients. CONCLUSION: Results cast
      doubt on whether this simple auditory stimulation paradigm, which requires
      cognitive action from the listener, is sensitive enough to discriminate between
      patients with DOC. SIGNIFICANCE: The sensitivity of the P300 ERP obtained in a
      short two-tone oddball paradigm presented in a passive and an active condition
      appears to be too low for routine application in a clinical setting aiming at
      distinguishing between VS and MCS patients.

PMID- 26315367
TI  - A case of upper limb chronic motor axonopathy with reversal of conduction failure
      and activity-dependent conduction block after immunomodulatory treatment.

PMID- 26315368
TI  - Evaluation of extensor digitorum brevis thickness in healthy subjects: A
      comparative analysis of nerve conduction studies and ultrasound scans.
AB  - OBJECTIVES: (1) To evaluate the relationship between the thickness and compound
      muscle action potential (CMAP) of the extensor digitorum brevis (EDB) muscle; (2)
      to obtain reference values for distal lower extremity muscle thickness as a
      possible measure of peripheral neuropathy; and (3) to evaluate various factors
      associated with unexplained EDB atrophy. METHODS: We measured the thickness of
      EDB, abductor hallucis brevis (AHB) and tibialis anterior (TA) muscles in 80
      healthy volunteers with ultrasound and assessed EDB CMAP with fibular nerve
      stimulation. Two foot muscle-associated lifestyle factors were assessed and
      sociodemographic information was collected. RESULTS: A significant correlation
      was observed between the amplitude of the fibular nerve CMAP and EDB thickness.
      The thickness of each of the three muscles was greater in men compared to women.
      EDB thickness decreased significantly with age although the thicknesses of the
      AHB and TA muscles were not correlated with age. CONCLUSIONS: EDB thickness was
      closely associated with fibular nerve CMAP but with less variation and differed
      among groups by age and sex; it was not associated with lifestyle factors.
      SIGNIFICANCE: The ability to obtain this measure painlessly with ultrasound and
      its low variation recommend it as a potentially useful complementary measure of
      distal neuromuscular function.

PMID- 26315369
TI  - Adenomyosis: what is new?
AB  - Adenomyosis is described as the benign invasion of endometrium into the
      myometrium, with endometrial glands and stroma surrounded by the hypertrophic and
      hyperplastic myometrium. It may affect 20% of female population and most widely
      seen among perimenopausal and multiparous women. Its etiopathogenesis, diagnosis,
      clinical findings and current various treatment options will be discussed in this
      article. 

PMID- 26315371
TI  - Corrigendum: GABA signalling modulates plant growth by directly regulating the
      activity of plant-specific anion transporters.

PMID- 26315370
TI  - The anti-inflammatory glycoprotein, CD200, restores neurogenesis and enhances
      amyloid phagocytosis in a mouse model of Alzheimer's disease.
AB  - Cluster of Differentiation-200 (CD200) is an anti-inflammatory glycoprotein
      expressed in neurons, T cells, and B cells, and its receptor is expressed on
      glia. Both Alzheimer's disease patients and mouse models display age-related or
      amyloid-beta peptide (Abeta)-induced reductions in CD200. The goal of this study
      was to determine if neuronal CD200 expression restores hippocampal neurogenesis
      and reduces Abeta in the amyloid precursor protein mouse model. Amyloid precursor
      protein and wild-type mice were injected at 6 months of age with an adeno
      associated virus expressing CD200 into the hippocampus and sacrificed at 12
      months. CD200 expression restored neural progenitor cell proliferation and
      differentiation in the subgranular and granular cell layers of the dentate gyrus
      and reduced diffuse but not thioflavin-S(+) plaques in the hippocampus. In vitro
      studies demonstrated that CD200-stimulated microglia increased neural
      differentiation of neural stem cells and enhanced axon elongation and dendrite
      number. CD200 also enhanced Abeta uptake by microglia. These data indicate that
      CD200 is capable of enhancing microglia-mediated Abeta clearance and neural
      differentiation and has potential as a therapeutic for Alzheimer's disease. 

PMID- 26315372
TI  - Review article: quality of follow-up care for anaphylaxis in the emergency
      department.
AB  - The prevalence of allergic disorders is rising, with a corresponding increase in
      patients presenting to an ED with anaphylaxis. Appropriate follow up is required
      for patients with anaphylaxis. We reviewed two potential performance indicators
      for the quality of post-discharge care: (i) the rate of self-injectable
      adrenaline prescription; and (ii) the referral rate for follow-up care with
      allergy specialists. A search of Cochrane Library, PubMed and Google Scholar was
      performed using the following initial search string: anaphylaxis and 'emergency
      department'. We considered any (interventional or observational design) study
      assessing post-discharge care in anaphylaxis, measured by either adrenaline self
      injection prescription or allergist referral. Subjects were patients with
      (suspected) anaphylaxis or severe allergic reaction, with no age limit. This
      review summarises findings from 16 relevant papers, all retrospective analyses of
      post-discharge care for anaphylaxis. Weighted arithmetic means were calculated
      for rates of prescription of adrenaline auto-injector and referral to an
      allergist following admission to an ED in patients with (suspected) anaphylaxis
      or severe allergic reaction. Prescription rates for self-injected adrenaline at
      the time of discharge following anaphylaxis varied from 0% to 68%, with a mean of
      44%. Allergist referral rates ranged from 0% to 84%, with a mean of 33%. This
      review demonstrates that there is room for improvement in post-discharge care for
      patients who present to the ED with an anaphylactic reaction. 

PMID- 26315373
TI  - Energy metabolism and the high-altitude environment.
AB  - At high altitude the barometric pressure falls, challenging oxygen delivery to
      the tissues. Thus, whilst hypoxia is not the only physiological stress
      encountered at high altitude, low arterial P(O2) is a sustained feature, even
      after allowing adequate time for acclimatization. Cardiac and skeletal muscle
      energy metabolism is altered in subjects at, or returning from, high altitude. In
      the heart, energetic reserve falls, as indicated by lower phosphocreatine-to-ATP
      ratios. The underlying mechanism is unknown, but in the hypoxic rat heart fatty
      acid oxidation and respiratory capacity are decreased, whilst pyruvate oxidation
      is also lower after sustained hypoxic exposure. In skeletal muscle, there is not
      a consensus. With prolonged exposure to extreme high altitude (>5500 m) a loss of
      muscle mitochondrial density is seen, but this was not observed in a simulated
      ascent of Everest in hypobaric chambers. At more moderate high altitude,
      decreased respiratory capacity may occur without changes in mitochondrial volume
      density, and fat oxidation may be downregulated, although this is not seen in all
      studies. The underlying mechanisms, including the possible role of hypoxia
      signalling pathways, remain to be resolved, particularly in light of confounding
      factors in the high-altitude environment. In high-altitude-adapted Tibetan
      natives, however, there is evidence of natural selection centred around the
      hypoxia-inducible factor pathway, and metabolic features in this population (e.g.
      low cardiac phosphocreatine-to-ATP ratios, increased cardiac glucose uptake and
      lower muscle mitochondrial densities) share similarities with those in
      acclimatized lowlanders, supporting a possible role for the hypoxia-inducible
      factor pathway in the metabolic response of cardiac and skeletal muscle energy
      metabolism to high altitude.

PMID- 26315374
TI  - Thyroid function and autoimmunity in Danish pregnant women after an iodine
      fortification program and associations with obstetric outcomes.
AB  - OBJECTIVE: Aberrations in maternal thyroid function and autoimmunity during
      pregnancy have been associated with negative obstetric outcome. In Denmark, a
      national iodine fortification program was implemented in the year 2000 with the
      aim to alleviate the mild-moderate iodine deficiency. Following the iodine
      implementation, there has been an increase in thyroid autoimmunity in the
      background population. This study investigates the thyroid status of pregnant
      Danish women following the iodine fortification program, and a possible
      association with preterm delivery. DESIGN: Historical cohort study of 1278
      randomly selected pregnant Danish women attending the national Down's syndrome
      screening program. METHODS: The main outcome measures were thyroid status
      according to laboratory- and gestational-age-specific reference intervals, and
      association with risk of abnormal obstetric outcome. Antibody-positivity was
      defined as an antibody-level (thyroid peroxidase and/or thyroglobulin antibodies)
      above 60 U/ml. RESULTS: Establishing laboratory-specific gestational-age
      dependent reference intervals, we found a prevalence of maternal thyroid
      dysfunction of 10%-15.8% by use of the cut-off suggested by the American Thyroid
      Association. Thyroid dysfunction was significantly associated with antibody
      positivity (P<0.05). No associations were found between preterm delivery and
      thyroid dysfunction (adjusted OR 0.6, 95% CI: 0.1-2.3) or autoimmunity (adjusted
      OR 1.1, 95% CI: 0.4-2.7). CONCLUSIONS: After the implementation of the Danish
      iodine fortification program, the prevalence of thyroid dysfunction and
      autoimmunity in Danish pregnant women is high - even higher by use of pre
      established reference intervals from international consensus guidelines. However,
      no associations were found with abnormal obstetric outcome. Large randomized
      controlled trials are needed to clarify the benefit of treating slight
      aberrations in pregnant women's thyroid function.

PMID- 26315375
TI  - LC-MS/MS based determination of basal- and ACTH-stimulated plasma concentrations
      of 11 steroid hormones: implications for detecting heterozygote CYP21A2 mutation
      carriers.
AB  - OBJECTIVE: Heterozygosity in 21-hydroxylase deficiency (21OHD) has been
      associated with hyperandrogenemic symptoms in children and adults. Moreover, the
      carrier status is mandatory for genetic counseling. We aimed at defining a
      hormonal parameter for carrier detection by mass spectrometry. DESIGN: Eleven
      basal and ACTH-stimulated steroid hormones of heterozygous carriers of CYP21A2
      mutations and control individuals were compared. METHOD: Hormones were determined
      in plasma samples by liquid chromatography tandem mass spectrometry (LC-MS/MS) in
      58 carriers (35 males, 23 females, age range 6-78 years) and 44 random controls
      (25 males, 19 females, age range 8-58 years). RESULTS: Heterozygotes could be
      identified best applying the 17-hydroxyprogesterone+21
      deoxycortisol/cortisol*1000 ((17OHP+21S)/F*1000) equation 30  min after ACTH
      injection. An optimal cut-off value of 8.4 provided 89% sensitivity and
      specificity. Considering this data and a published frequency of heterozygotes of
      1/50 to 1/61, the positive predictive value (PPV) of this cut-off is 12%. Of
      note, the negative predictive value (NPV) excluding heterozygosity in a given
      patient is 99.8%. CONCLUSION: Considering only marginal biochemical effects
      anticipated from heterozygosity, the stimulated ((17OHP+21S)/F*1000) identifies
      and excludes heterozygotes remarkably well. Nevertheless, LC-MS/MS cannot replace
      genetic testing, since sensitivity and specificity did not reach 100%. However,
      due to the considerably high NPV of the optimal cut-off and to a specificity of
      even 100% applying a cut-off higher than 14.7, hormonal assessment of
      heterozygosity can be of significant aid in conditions with limited access to
      genetic testing, as in some health care systems. The ((17OHP+21S)/F*1000)
      equation can guide diagnostic considerations in the differential diagnosis of
      hyperandrogenism.

PMID- 26315376
TI  - Sustained delivery of chondroitinase ABC by poly(propylene carbonate)-chitosan
      micron fibers promotes axon regeneration and functional recovery after spinal
      cord hemisection.
AB  - We describe the sustained delivery of chondroitinase ABC (ChABC) in the
      hemisected spinal cord using polypropylene carbonate (PPC) electrospun fibers
      with chitosan (CS) microspheres as a vehicle. PPC and ChABC-loaded CS
      microspheres were mixed with acetonitrile, and micron fibers were generated by
      electrospinning. ChABC release was assessed in vitro with high-performance liquid
      chromatography (HPLC) and revealed stabilized and prolonged release. Moreover,
      the released ChABC showed sustained activity. PPC-CS micron fibers with or
      without ChABC were then implanted into a hemisected thoracic spinal cord. In the
      following 4 weeks, we examined functional recovery and performed
      immunohistochemical analyses. We found that sustained delivery of ChABC promoted
      axon sprouting and functional recovery and reduced glial scarring; PPC-CS micron
      fibers without ChABC did not show these effects. The present findings suggest
      that PPC-CS micron fibers containing ChABC are a feasible option for spinal cord
      injury treatment. Furthermore, the system described here may be useful for local
      delivery of other therapeutic agents. 

PMID- 26315377
TI  - A rat model of chronic subdural hematoma: Insight into mechanisms of
      revascularization and inflammation.
AB  - Chronic subdural hematoma (CSDH) is a common neurological occurrence in the
      elderly population with significant impact on the quality of life and work.
      Studies have attempted to determine the risk factors and pathophysiological
      mechanisms of CSDH using models in numerous mammalian species. To date, these
      animal models have only been able to reproduce limited durations of hematoma
      which does not accurately reflect the chronic state of CSDH. To address some of
      these challenges we modified a rat model of CSDH using two consecutive injections
      of autologous blood resulting in a hematoma of more than three weeks. We observed
      inflammatory and angiogenic changes related to the development and recovery of
      CSDH. In this study the technique for producing a CSDH in a small animal model
      had a success rate of 78.13%. The hematoma was sustainable up to 24 days.
      Hematoma resolution was associated with a gradual decrease in local pro
      inflammatory factors and gradual increase in anti-inflammatory factors as well as
      proliferation and subsequent maturation of newly formed vessels. These events
      were also associated with improved behavioral outcome. Expression of anti
      inflammatory cytokines also paralleled reabsorption of the hematoma. Reduction in
      hematoma size was also associated with neurological recovery. These data suggest
      that vessel maturation and anti-inflammatory pathways may contribute to the
      resolution of CSDH and neurological recovery. The regulation of the two
      mechanisms is a potential target for the treatment of CSDH. The modified model of
      rat CSDH demonstrated a high level of reproducibility in our hands and may be
      useful in future CSDH studies. 

PMID- 26315378
TI  - Temporal profile of the vascular anatomy evaluated by 9.4-tesla magnetic
      resonance angiography and histological analysis in mice with the R4859K mutation
      of RNF213, the susceptibility gene for moyamoya disease.
AB  - Moyamoya disease (MMD) is a chronic, occlusive cerebrovascular disease with an
      unknown etiology. Recent genome-wide and locus-specific association studies
      identified the RNF213 gene (RNF213) as an important susceptibility gene of MMD
      among East Asian populations; however, the mechanism by which an abnormality in
      RNF213 leads to MMD has not yet been elucidated. Therefore, we herein generated
      Rnf213-knock-in mice (RNF213-KI) expressing a missense mutation in mouse Rnf213,
      p. R4828K, on Exon 61, corresponding to human RNF213, p. R4859K, on Exon 60, in
      MMD patients, and investigated whether they developed MMD. We assessed the
      temporal profile of intracranial arteries by 9.4-T magnetic resonance angiography
      (MRA) continuously in the same mouse up to 64 weeks of age. The ratios of the
      outer diameter of the internal carotid artery (ICA)/basilar artery (BA) and
      middle cerebral artery (MCA)/BA were evaluated histopathologically. The common
      carotid arteries (CCA) were sectioned and arterial wall thickness/thinness was
      evaluated by Elastica-Masson staining before and after CCA ligation, which
      selectively induced vascular hyperplasia. The results obtained showed that RNF213
      KI grew normally, with no significant difference being observed in MRA findings
      or the anatomy of the circle of Willis between homozygous RNF213-KI and wild-type
      (Wt) littermates. Furthermore, no significant difference was noted in the
      diameter of the intracranial vasculature (ICA/BA; p=0.82, MCA/BA; p=0.27) or in
      vascular remodeling after CCA ligation. Therefore, RNF213-KI did not
      spontaneously develop MMD. Multiple secondary insults such as environmental
      factors may contribute to the onset of MMD in addition to genetic factors. 

PMID- 26315379
TI  - Fatigue in Primary Sjogren's Syndrome: Clinical, Laboratory, Psychometric, and
      Biologic Associations.
AB  - OBJECTIVE: To identify independent contributors of fatigue in primary Sjogren's
      syndrome (SS) patients, taking into account clinical, laboratory, and
      psychological features, and to explore the potential role of interferon (IFN)
      induced gene indoleamine 2,3-dioxygenase (IDO-1), anti-21-hydroxylase (anti
      21[OH]) antibodies, and soluble BAFF. METHODS: Detailed clinical and laboratory
      characteristics were recorded for 106 primary SS patients. The Functional
      Assessment of Chronic Illness Therapy-Fatigue, Zung Depression Scale, State-Trait
      Anxiety Inventory, Eysenck Personality Questionnaire Scale, and Athens Insomnia
      Scale were adopted to assess fatigue, depression, anxiety, and sleep
      disturbances, respectively. Peripheral whole blood expression levels of IDO-1, as
      well as type I and II IFN-induced genes were calculated using quantitative
      reverse transcriptase-polymerase chain reaction. Serum anti-21(OH) antibodies and
      soluble BAFF levels were determined by a radioimmunoassay and an enzyme-linked
      immunosorbent assay, respectively. Univariate and multivariate models were
      performed to identify determinants of fatigue. RESULTS: Fatigue was detected in
      32 of 106 (30.2%) primary SS patients. In univariate analysis, fatigue was
      associated with arthralgias/myalgias, fibromyalgia hydroxychloroquine therapy,
      both state and trait anxiety scores, depression, and neuroticism, as well as
      impaired sleep patterns. Multivariate analysis revealed neuroticism (odds ratio
      [OR] 6.9, [95% confidence interval (95% CI) 1.7-28.0]), depression (OR 3.0 [95%
      CI 0.8-11.0]), and fibromyalgia (OR 5.5 [95% CI 1.1-27.7]) as independent fatigue
      contributors. Soluble BAFF levels, anti-21(OH) autoantibodies, and IDO-1
      messenger RNA expression did not significantly differ between fatigued and
      nonfatigued primary SS patients. CONCLUSION: Depression, neuroticism, and
      fibromyalgia play a major role in primary SS-associated fatigue and should be
      addressed in clinical practice, with active collaboration between rheumatologists
      and mental health professionals. Further studies are warranted in order to
      explore underlying pathophysiologic pathways that might explain fatigue in the
      setting of primary SS.

PMID- 26315380
TI  - Synchronization Analysis of Master-Slave Probabilistic Boolean Networks.
AB  - In this paper, we analyze the synchronization problem of master-slave
      probabilistic Boolean networks (PBNs). The master Boolean network (BN) is a
      deterministic BN, while the slave BN is determined by a series of possible
      logical functions with certain probability at each discrete time point. In this
      paper, we firstly define the synchronization of master-slave PBNs with
      probability one, and then we investigate synchronization with probability one. By
      resorting to new approach called semi-tensor product (STP), the master-slave PBNs
      are expressed in equivalent algebraic forms. Based on the algebraic form, some
      necessary and sufficient criteria are derived to guarantee synchronization with
      probability one. Further, we study the synchronization of master-slave PBNs in
      probability. Synchronization in probability implies that for any initial states,
      the master BN can be synchronized by the slave BN with certain probability, while
      synchronization with probability one implies that master BN can be synchronized
      by the slave BN with probability one. Based on the equivalent algebraic form,
      some efficient conditions are derived to guarantee synchronization in
      probability. Finally, several numerical examples are presented to show the
      effectiveness of the main results. 

PMID- 26315381
TI  - Gastrointestinal cancers in inflammatory bowel disease: An update with emphasis
      on imaging findings.
AB  - Inflammatory bowel diseases (IBD) are associated with an increased risk of
      gastrointestinal cancers depending on the specific type of IBD, the extent of the
      disease and its location. Patients with IBD and extensive colonic involvement are
      at increased risk of colorectal cancer whereas patients with Crohn disease have
      an increased risk for small-bowel and anal carcinoma. These cancers
      preferentially develop on sites of longstanding inflammation. In regards to colon
      cancer, several key pathogenic events are involved, including chromosomal
      instability, microsatellite instability and hypermethylation. The risk for colon
      cancer in IBD patients correlates with longer disease duration, presence of
      sclerosing cholangitis, pancolitis, family history of colorectal cancer, early
      onset of the disease and severity of bowel inflammation. Identification of
      increased colorectal cancer risk in individual IBD patients has led to formal
      surveillance guidelines. Conversely, although an increased risk for other types
      of cancer has been well identified, no specific formal screening recommendations
      exist. Consequently, the role of the radiologist is crucial to alert the
      referring gastroenterologist when a patient with IBD presents with unusual
      imaging findings at either computed tomography (CT) or magnetic resonance (MR)
      imaging. This review provides an update on demographics, molecular, clinical and
      histopathological features of gastrointestinal cancers in IBD patients including
      colorectal carcinoma, small bowel adenocarcinoma, neuroendocrine tumors and anal
      carcinoma, along with a special emphasis on the current role of CT and MR
      imaging. 

PMID- 26315382
TI  - TP53 dysfunction in diffuse large B-cell lymphoma.
AB  - The aberrations of TP53 gene and dysregulation of the TP53 pathway are important
      in the pathogenesis of many human cancers, including malignant lymphomas,
      especially for diffuse large B cell lymphoma (DLBCL). By regulating many
      downstream target genes or molecules, TP53 governs major defenses against tumor
      growth and promotes cellular DNA repair, apoptosis, autophagy, cell cycle arrest,
      signaling, transcription, immune or inflammatory responses and metabolism.
      Dysfunction of TP53, including microRNA regulations, copy number alterations of
      TP53 pathway and TP53 itself, dysregulation of TP53 regulators, and somatic
      mutations by abnormal TP53 function modes, play an important role in lymphoma
      generation, progression and invasion. The role of TP53 in DLBCL has been widely
      explored recently. In this review, we summarized recent advances on different
      mechanisms of TP53 in DLBCL and new therapeutic approaches to overcome TP53
      inactivation. 

PMID- 26315383
TI  - Therapeutic hyperthermia: The old, the new, and the upcoming.
AB  - Hyperthermia has long been used for cancer treatment, either alone or in
      combination with chemotherapy, radiation therapy, or both. Its efficacy and
      versatility continue to be well demonstrated in randomized trials across a number
      of primary cancers, but barriers to its widespread adoption persist including
      effective delivery and verification systems. This article describes hyperthermia,
      details its biological mechanisms of action and immunological effects, and
      summarizes select preclinical data and key clinical trials combining hyperthermia
      with standard cancer treatments. Current challenges and emerging technologies
      that have the potential to make this translational therapy more accessible to a
      greater number of patients are also described. 

PMID- 26315385
TI  - Patterns of testosterone in three Nearctic-Neotropical migratory songbirds during
      spring passage.
AB  - Preparation for breeding may overlap extensively with vernal migration in long
      distance migratory songbirds. Testosterone plays a central role in mediating this
      transition into breeding condition by facilitating changes to physiology and
      behavior. While changes in testosterone levels are well studied in captive
      migrants, these changes are less well known in free-living birds. We examined
      testosterone levels in free-living Nearctic-Neotropical migrants of three species
      during their vernal migration. Testosterone levels increased during the migratory
      period in males of all three species but significantly so in only two.
      Testosterone levels in females remained the same throughout their migration. Our
      results support the extensive overlap between vernal migration and breeding
      preparation in male songbirds. The pattern of testosterone changes during vernal
      migration is far from clear in females. 

PMID- 26315384
TI  - Is the whole greater than the sum of its parts? De novo assembly strategies for
      bacterial genomes based on paired-end sequencing.
AB  - BACKGROUND: Whole genome sequence construction is becoming increasingly feasible
      because of advances in next generation sequencing (NGS), including increasing
      throughput and read length. By simply overlapping paired-end reads, we can obtain
      longer reads with higher accuracy, which can facilitate the assembly process.
      However, the influences of different library sizes and assembly methods on paired
      end sequencing-based de novo assembly remain poorly understood. RESULTS: We used
      250 bp Illumina Miseq paired-end reads of different library sizes generated from
      genomic DNA from Escherichia coli DH1 and Streptococcus parasanguinis FW213 to
      compare the assembly results of different library sizes and assembly approaches.
      Our data indicate that overlapping paired-end reads can increase read accuracy
      but sometimes cause insertion or deletions. Regarding genome assembly, merged
      reads only outcompete original paired-end reads when coverage depth is low, and
      larger libraries tend to yield better assembly results. These results imply that
      distance information is the most critical factor during assembly. Our results
      also indicate that when depth is sufficiently high, assembly from subsets can
      sometimes produce better results. CONCLUSIONS: In summary, this study provides
      systematic evaluations of de novo assembly from paired end sequencing data. Among
      the assembly strategies, we find that overlapping paired-end reads is not always
      beneficial for bacteria genome assembly and should be avoided or used with
      caution especially for genomes containing high fraction of repetitive sequences.
      Because increasing numbers of projects aim at bacteria genome sequencing, our
      study provides valuable suggestions for the field of genomic sequence
      construction.

PMID- 26315386
TI  - Fresh water acclimation elicits a decrease in plasma corticosteroids in the
      euryhaline Atlantic stingray, Dasyatis sabina.
AB  - It is thought that the elasmobranch corticosteroid hormone 1alpha
      hydroxycorticosterone (1alpha-B) functions as both a glucocorticoid (GC) and
      mineralocorticoid (MC). Classical antinatriuretic MC activities would run counter
      to the osmoregulatory strategy of euryhaline elasmobranchs acclimating to fresh
      water (FW). Therefore we hypothesize that FW acclimation will be accompanied by a
      decrease in plasma corticosteroids in these animals. However, events that
      activate the "fight-or-flight" response could mask changes associated with
      acclimation to lower salinities. To better define the MC role of corticosteroids
      in elasmobranchs, we designed a transfer system that allows the acclimation of
      Atlantic stingrays (Dasyatis sabina) from seawater (SW) to FW over 12h while
      minimizing other extraneous stressors. Blood and interrenal glands were sampled
      from one group of stingrays 24h after FW transfer, while another group was
      sampled two weeks after FW transfer. Two other groups served as mock-transfer
      controls in that they were treated and sampled in the same way, but remained in
      SW for the entire period. Plasma corticosteroids, osmolality, chloride, and urea
      were significantly lower in FW-acclimated stingrays (compared to mock-transfer
      stingrays) 24h after FW transfer. This pattern remained after two weeks in FW,
      with the exception that plasma corticosteroids returned to pre-acclimation
      levels. There were no significant differences between experimental groups in
      interrenal levels of mRNAs encoding key steroidogenic proteins (steroidogenic
      acute regulatory protein and cholesterol side chain cleavage enzyme). Temporally
      decreased corticosteroid levels during FW acclimation are consistent with the
      unique strategy of euryhaline elasmobranchs, whereby lower plasma osmolality is
      maintained in FW vs. SW environments to reduce hydromineral gradients. 

PMID- 26315387
TI  - New insights into the factors mediating the onset of puberty in sea bass.
AB  - In populations of 1-year-old male European sea bass (Dicentrarchus labrax), only
      large males are able to acquire for the first time a functional competence of
      their reproductive axis; in other words, to attain puberty. To examine the causes
      and mechanisms involved in the onset of puberty in this species, a size sorting
      sampling was carried out to obtain two experimental groups of small and large
      male fish exhibiting different growth rates. As expected, only large fish reached
      full spermiogenesis (stage V of testicular development) by the end of the
      experiment. Our study suggests that fish size is a permissive condition to ensure
      full effectiveness of the hormonal (Gnrh1, gonadotropins and sexual steroids)
      actions. Thus, though small fish had endocrine profiles similar to those of large
      fish, their amplitude was much lower, and was most likely the reason why
      functional competence of the reproductive axis was not achieved. Moreover, this
      work provides evidence of the involvement of kisspeptin and Gnrh1 systems in the
      onset of puberty in a marine teleost fish. It also indicates that very likely
      kisspeptin and Gnrh1 may regulate gonadotropins and sex steroids at specific
      stages of testicular development. 

PMID- 26315388
TI  - FSH and bFGF regulate the expression of genes involved in Sertoli cell energetic
      metabolism.
AB  - The purpose of this study was to investigate if FSH and bFGF regulate fatty acid
      (FA) metabolism and mitochondrial biogenesis in Sertoli cells (SC). SC cultures
      obtained from 20-day-old rats were incubated with 100ng/ml FSH or 30ng/ml bFGF
      for 6, 12, 24 and 48h. The expression of genes involved in transport and
      metabolism of FA such as: fatty acid transporter CD36 (FAT/CD36), carnitine
      palmitoyltransferase 1 (CPT1), long- and medium-chain 3-hydroxyacyl-CoA
      dehydrogenases (LCAD, MCAD), and of genes involved in mitochondrial biogenesis
      such as: nuclear respiratory factors 1 and 2 (NRF1, NRF2) and transcription
      factor A (Tfam), was analyzed. FSH stimulated FAT/CD36, CPT1, MCAD, NRF1, NRF2
      and Tfam mRNA levels while bFGF only stimulated CPT1 expression. A possible
      participation of PPARbeta/delta activation in the regulation of gene expression
      and lactate production was then evaluated. SC cultures were incubated with FSH or
      bFGF in the presence of the PPARbeta/delta antagonist GSK3787 (GSK; 20MUM). bFGF
      stimulation of CPT1 expression and lactate production were inhibited by GSK. On
      the other hand, FSH effects were not inhibited by GSK indicating that FSH
      regulates the expression of genes involved in FA transport and metabolism and in
      mitochondrial biogenesis, independently of PPARbeta/delta activation. FA
      oxidation and mitochondrial biogenesis as well as lactate production are
      essential for the energetic metabolism of the seminiferous tubule. The fact that
      these processes are regulated by hormones in a different way reflects the
      multifarious regulation of molecular mechanisms involved in Sertoli cell
      function. 

PMID- 26315389
TI  - Determination of plasma kisspeptin concentrations during reproductive cycle and
      different phases of pregnancy in crossbred cows using bovine specific enzyme
      immunoassay.
AB  - Kisspeptin, a decapeptide and potent secretagogue of GnRH has been emerged
      recently as a master player in the regulation of reproduction in animals.
      Determination of kisspeptin in peripheral circulation is, therefore, very
      important for studying the control of its secretion and its role on reproduction
      in bovine species, the information on which is not available during any
      physiological state in this species, may probably be due to non-availability of
      simple assay procedure to measure the hormone. Therefore, the objective of this
      study was to develop and validate a simple and sufficiently sensitive enzyme
      immunoassay (EIA) for kisspeptin determination in bovine plasma using the biotin
      streptavidin amplification system and second antibody coating technique. Biotin
      was coupled to kisspeptin and used to bridge between streptavidin-peroxidase and
      the immobilized kisspeptin antiserum in the competitive assay. The EIA was
      conducted directly in 100 MUl of unknown bovine plasma. Kisspeptin standards
      ranging from 0.01 to 25.6 ng/100 MUl/well were prepared in hormone-free plasma.
      The lowest detection limit was 0.1 ng/ml plasma. Plasma volumes for the EIA,
      viz., 50, 100 and 200 MUl did not influence the shape of standard curve even
      though a drop in OD450 was seen with higher plasma volumes. A parallelism test
      was carried out to compare the endogenous bovine kisspeptin with kisspeptin
      standard used. It showed good parallelism with the kisspeptin standard curve. For
      the biological validation of the assay, plasma kisspeptin was measured in blood
      samples collected from six non-lactating cyclic cows during entire estrous cycle
      and from 18 pregnant cows during different stages of pregnancy. The mean plasma
      kisspeptin concentration during different days of the estrous cycle was different
      (P<0.001). Three peaks of kisspeptin were recorded, one on a day before
      appearance of preovulatory LH surge, second at day 6 and third one at day 18 of
      the estrous cycle. Plasma kisspeptin concentrations increased (P<0.001) from
      first through last trimester of pregnancy. Kisspeptin concentrations were also
      measured in different follicular, luteal and placental tissues. Follicular and
      placental kisspeptin levels increased (P<0.01) during follicular development and
      with the advancement of pregnancy, respectively. On the other hand, luteal
      concentrations of kisspeptin decreased (P<0.01) with its developmental process.
      In conclusion, a simple, sufficiently sensitive and direct EIA procedure has been
      developed for the first time to determine plasma kisspeptin levels in bovine. A
      wide range of kisspeptin concentrations can be detected during different
      physiological stages in bovine using this kisspeptin-EIA procedure.

PMID- 26315390
TI  - Altered corticostriatal functional connectivity in individuals with high social
      anhedonia.
AB  - BACKGROUND: Dysregulation of the striatum and altered corticostriatal
      connectivity have been associated with psychotic disorders. Social anhedonia has
      been identified as a predictor for the development of schizophrenia spectrum
      disorders. The aim of the present study was to examine corticostriatal functional
      connectivity in individuals with high social anhedonia. METHOD: Twenty-one
      participants with high social anhedonia score and 30 with low social anhedonia
      score measured by the Chinese version of the Revised Social Anhedonia Scale were
      recruited from university undergraduates (age 17-21 years) to undergo resting
      state functional MRI scans. Six subdivisions of the striatum in each hemisphere
      were defined as seeds. Voxel-wise functional connectivity analyses were conducted
      between each seed and the whole brain voxels, followed by repeated-measures ANOVA
      for the group effect. RESULTS: Participants with high social anhedonia showed
      hyper-connectivity between the ventral striatum and the anterior cingulate cortex
      and the insula, and between the dorsal striatum and the motor cortex. Hypo
      connectivity in participants with high social anhedonia was also observed between
      the ventral striatum and the posterior cingulate cortex. Partial correlation
      analyses further showed that the functional connectivity between the ventral
      striatum and the prefrontal cortex was associated with pleasure experience and
      emotional suppression. CONCLUSIONS: Our findings suggest that altered
      corticostriatal connectivity can be found in participants with high levels of
      social anhedonia. Since social anhedonia has been considered a predictor for
      schizophrenia spectrum disorders, our results may provide novel evidence on the
      early changes in brain functional connectivity in at-risk individuals.

PMID- 26315391
TI  - [Augmentation with PMMA cement].
AB  - Cements based on polymethyl methacrylate (PMMA) can be used without any problem
      in a variety of clinical augmentations. Cement-related complications in surgical
      procedures involving PMMA cements, such as embolism, thermal necrosis, toxicity
      and hypersensitivity, are often due to other causes. Knowledge about the
      properties of the cement helps the user to safely employ PMMA cements in
      augmentations. High radio-opacity is required in vertebral body augmentations and
      this is provided in particular by zirconium dioxide. In vertebral body
      augmentations, a low benzoyl peroxide (BPO) content can considerably prolong the
      liquid dough phase. In augmentations with cement fillings in the region of a
      tumor, a high BPO content can specifically increase the peak temperature of the
      PMMA cement. In osteosynthetic augmentations with PMMA, necrosis is rare because
      heat development in the presence of metallic implants is low due to heat
      conduction via the implant. Larger cement fillings where there is no heat
      conduction via metal implants can exhibit substantially higher peak temperatures.
      The flow properties of PMMA cements are of particular importance for the user to
      allow optimum handling of PMMA cements. In patients with hypersensitivity to
      antibiotics, there is no need to avoid the use of PMMA as there are sufficient
      PMMA-based alternatives. The PMMA cements are local drug delivery systems and
      antibiotics, antiseptics, antimycotics and also cytostatics can be mixed with the
      cement. Attention must be paid to antagonistic and synergistic effects.

PMID- 26315392
TI  - Discovery of bioactive molecules from CuAAC click-chemistry-based combinatorial
      libraries.
AB  - The rapid assembly and in situ screening of focused combinatorial fragment
      libraries using CuAAC click chemistry is a highly robust and efficient strategy
      for establishing SAR and for discovering bioactive molecules. This review
      outlines the current status of this methodology in drug discovery application.
      The inherent limitations, challenges and prospects are critically discussed. 

PMID- 26315394
TI  - The Diagnostic Value of Routine Papanicolaou Smears for Detecting Endometrial
      Cancers: An Update.
AB  - OBJECTIVE: The presence of degenerative endometrial debris and abnormal
      endometrial cells is considered to be the hint for endometrial pathology. The
      purpose of this study was to evaluate the efficacy of Papanicolaou (Pap) smears
      in detecting endometrial cancers. STUDY DESIGN: There were 146 cases of
      endometrial cancer diagnosed at our institute in 2000-2002 and 271 in 2010-2012.
      Among them, 57 and 95 relevant reports of Pap smears 6 months prior to the
      histology diagnosis were retrieved for this study, respectively. In the first
      time period, new criteria for detecting endometrial lesions had not yet been
      incorporated into routine screening. RESULTS: Twenty cases (21%) of
      adenocarcinoma, 12 (13%) of atypical glandular cells, 4 (4%) of endometrial
      debris and 59 (62%) negative reports were found among the more recent 95 relevant
      Pap smears. The overall efficacy of the Pap smear for detecting endometrial
      malignancy was 38%, higher than 10 years previously (30%). CONCLUSION: Although
      the Pap smear was originally designed to screen cervical lesions, more effective
      detection of endometrial lesions could be achieved by adding new criteria to the
      routine screening.

PMID- 26315393
TI  - Regulation of Cholesterol Homeostasis by Hedgehog Signaling in Osteoarthritic
      Cartilage.
AB  - OBJECTIVE: With no effective therapies to attenuate cartilage degeneration in
      osteoarthritis (OA), the result is pain and disability. Activation of hedgehog
      (HH) signaling causes changes related to the progression of OA, with higher
      levels of Gli-mediated transcriptional activation associated with increased
      disease severity. To elucidate the mechanism through which this occurs, this
      study sought to identify genes regulated by HH signaling in human OA
      chondrocytes. METHODS: Using human OA cartilage samples, microarray analyses were
      performed to detect changes in gene expression when the HH pathway was modulated.
      Results were analyzed for differentially expressed genes, grouped into functional
      networks, and validated in independent samples. To investigate the effects of
      chondrocyte-specific sterol accumulation, we generated mice lacking Insig1 and
      Insig2, which are major negative regulators of cholesterol homeostasis, under
      Col2a1 regulatory elements. RESULTS: HH signaling was found to regulate genes
      that govern cholesterol homeostasis, and this led to alterations in cholesterol
      accumulation in chondrocytes. A higher level of Gli-mediated transcription
      resulted in accumulation of intracellular cholesterol. In genetically modified
      mice, chondrocyte-specific cholesterol accumulation was associated with an OA
      phenotype. Reducing cholesterol accumulation attenuated the severity of OA in
      mice in vivo and decreased the expression of proteases in human OA cartilage in
      vitro. CONCLUSION: HH signaling regulates cholesterol homeostasis in
      chondrocytes, and intracellular cholesterol accumulation contributes to the
      severity of OA. Our findings have therapeutic implications, since reduction of HH
      signaling reversed cholesterol accumulation and statin treatment attenuated
      cartilage degeneration.

PMID- 26315395
TI  - Clinicopathological characteristics and management of prostate cancer in the
      human immunodeficiency virus (HIV)-positive population: experience in an
      Australian major HIV centre.
AB  - OBJECTIVES: To characterise clinicopathological characteristics of prostate
      cancer among human immunodeficiency virus (HIV)-positive men and to evaluate the
      current practice patterns in the management of prostate cancer in these men.
      PATIENTS AND METHODS: We retrospectively reviewed all patients with HIV in the
      State-wide HIV referral centre in Victoria, who were diagnosed with prostate
      cancer from 2000 onwards. In all, 12 patients were identified, and the medical
      records were reviewed to collect data on HIV parameters at the time of prostate
      cancer diagnosis, as well as prostate cancer clinicopathological characteristics,
      treatment details and outcomes. RESULTS: At the time of prostate cancer
      diagnosis, eight patients had undetectable viral load, and the median cluster of
      differentiation 4 (CD4) count was 485 cells/MUL. The average age at diagnosis of
      prostate cancer was 63 years and the median prostate-specific antigen (PSA) level
      of 11.1 ng/mL. Four patients had Gleason 6 prostate cancer, four Gleason 7, one
      Gleason 8 and three Gleason 9. Seven of the 12 patients had a positive family
      history for prostate cancer. Of the patients with clinically localised prostate
      cancer (10), most were treated with radiotherapy (RT): one permanent seed
      brachytherapy (BT), five external beam RT (EBRT), two open radical
      prostatectomies (RP), one active surveillance (AS), and one on watchful waiting
      (WW). For the two patients with metastatic disease, one had androgen-deprivation
      therapy and EBRT, while the other had a combination of EBRT and chemo-hormonal
      therapy with doxetacel. All patients were followed for a median of 46 months,
      with three deaths reported, none of which was a prostate cancer-specific death.
      CONCLUSIONS: This is the first Australasian series on prostate cancer management
      in a HIV population. With the prolonged survival among HIV-positive men in the
      highly active anti-retroviral therapy era, PSA testing should be offered to this
      group of patients, especially those with a positive family history. HIV-positive
      men should also be offered all treatment options in the same manner as men in the
      general population.

PMID- 26315396
TI  - EMT-induced metabolite signature identifies poor clinical outcome.
AB  - Metabolic reprogramming is a hallmark of cancer. Epithelial-mesenchymal
      transition (EMT) induces cancer stem cell (CSC) characteristics and promotes
      tumor invasiveness; however relatively little is known about the metabolic
      reprogramming in EMT. Here we show that breast epithelial cells undergo metabolic
      reprogramming following EMT. Relative to control, cell lines expressing EMT
      transcription factors show >=1.5-fold accumulation of glutamine, glutamate, beta
      alanine and glycylleucine as well as >=1.5-fold reduction of phosphoenolpyruvate,
      urate, and deoxycarnitine. Moreover, these metabolic alterations were found to be
      predictive of overall survival (hazard ratio = 2.3 (95% confidence interval: 1.31
      4.2), logrank p-value = 0.03) and define breast cancer molecular subtypes. EMT
      associated metabolites are primarily composed of anapleurotic precursors,
      suggesting that cells undergoing EMT have a shift in energy production. In
      summary, we describe a unique panel of metabolites associated with EMT and
      demonstrate that these metabolites have the potential for predicting clinical and
      biological characteristics associated with patient survival. 

PMID- 26315397
TI  - Enzymes in the in-situ pellicle of children with different caries activity.
AB  - The present study investigated, for the first time, enzymes in the in-situ
      pellicle of children. Furthermore, it was purposed to detect glucosyltransferase
      (GTF) isoforms in each child's pellicle. Twenty-four children (5-9 yr of age)
      participated in the study. Twelve were caries free with no decayed, missing, and
      filled teeth (dmft), whereas 12 had active caries (dmft >= 2, indicating at least
      two untreated carious lesions). Bovine enamel slabs, fixed on individual upper
      jaw splints, were utilized for pellicle formation in situ. After 3 and 30 min,
      samples were tested for amylase, lysozyme, and peroxidase activities; total GTF
      activity was examined only in the 30-min pellicle. Gold-immunolabelling was used
      to quantify the GTF B, C, and D isoforms in the pellicle by transmission electron
      microscopy (TEM). All enzymes tested were detected in the children's in-situ
      pellicle in an active conformation, and there were no significant differences in
      their levels of activity between caries-free and caries-active children. All GTF
      isoforms were found to be randomly distributed within all pellicle layers,
      althoug GTF B was only detected very sporadically. A significantly higher amount
      of GTF D was detected in the pellicle of caries-active children. Pellicle
      formation in children is characterized by uniformity and selectivity.
      Glucosyltransferase D might represent a possible biomarker for high caries risk
      in children.

PMID- 26315398
TI  - The effectiveness of an integrated collaborative care model vs. a shifted
      outpatient collaborative care model on community functioning, residential
      stability, and health service use among homeless adults with mental illness: a
      quasi-experimental study.
AB  - BACKGROUND: Although a growing number of collaborative mental health care models
      have been developed, targeting specific populations, few studies have utilized
      such interventions among homeless populations. This quasi-experimental study
      compared the outcomes of two shelter-based collaborative mental health care
      models for men experiencing homelessness and mental illness: (1) an integrated
      multidisciplinary collaborative care (IMCC) model and (2) a less resource
      intensive shifted outpatient collaborative care (SOCC) model. METHODS: In total
      142 participants, 70 from IMCC and 72 from SOCC were enrolled and followed for 12
      months. Outcome measures included community functioning, residential stability,
      and health service use. Multivariate regression models were used to compare study
      arms with respect to change in community functioning, residential stability, and
      health service use outcomes over time and to identify baseline demographic,
      clinical or homelessness variables associated with observed changes in these
      domains. RESULTS: We observed improvements in both programs over time on measures
      of community functioning, residential stability, hospitalizations, emergency
      department visits and community physician visits, with no significant differences
      between groups over time on these outcome measures. CONCLUSIONS: Our findings
      suggest that shelter-based collaborative mental health care models may be
      effective for individuals experiencing homelessness and mental illness. Future
      studies should seek to confirm these findings and examine the cost effectiveness
      of collaborative care models for this population.

PMID- 26315399
TI  - Cortical thickness predicts the first onset of major depression in adolescence.
AB  - Given the increasing prevalence of Major Depressive Disorder and recent advances
      in preventative treatments for this disorder, an important challenge in pediatric
      neuroimaging is the early identification of individuals at risk for depression.
      We examined whether machine learning can be used to predict the onset of
      depression at the individual level. Thirty-three never-disordered adolescents (10
      15 years old) underwent structural MRI. Participants were followed for 5 years to
      monitor the emergence of clinically significant depressive symptoms. We used
      support vector machines (SVMs) to test whether baseline cortical thickness could
      reliably distinguish adolescents who develop depression from adolescents who
      remained free of any Axis I disorder. Accuracies from subsampled cross-validated
      classification were used to assess classifier performance. Baseline cortical
      thickness correctly predicted the future onset of depression with an overall
      accuracy of 70% (69% sensitivity, 70% specificity; p=0.021). Examination of SVM
      feature weights indicated that the right medial orbitofrontal, right precentral,
      left anterior cingulate, and bilateral insular cortex contributed most strongly
      to this classification. These findings indicate that cortical gray matter
      structure can predict the subsequent onset of depression. An important direction
      for future research is to elucidate mechanisms by which these anomalies in gray
      matter structure increase risk for developing this disorder. 

PMID- 26315400
TI  - Mediobasal hypothalamic and adenohypophyseal TRH-degrading enzyme (PPII) is down
      regulated by zinc deficiency.
AB  - Thyrotropin-releasing hormone (TRH) synthesized in hypothalamic paraventricular
      nucleus directs hypothalamus-pituitary-thyroid (HPT) axis function, regulating
      thyrotropin release from adenohypophysis and thyroid hormones serum
      concentration. Pyroglutamyl aminopeptidase II (PPII), a Zn-dependent
      metallopeptidase located in adenohypophysis and medial-basal-hypothalamus
      degrades TRH released from the median eminence and participates in HPT axis
      function by regulating TRH-induced thyrotropin release from adenohypophysis. It
      is unknown whether dietary Zn deficiency down-regulates PPII. Our aim was to
      compare adenohypohyseal and medial-basal-hypothalamic PPII activity and
      expression of adult rats fed a Zn-deficient diet (2ppm) throughout their lifespan
      (DD), prenatally (DC) or after weaning (CD) vs. that of animals fed a control
      diet (20ppm:CC). Female rats consumed a Zn-deficient or control diet from two
      weeks before gestation and up to the end of lactation. We analyzed
      adenohypophyseal and medial-basal-hypothalamic PPII activity of dams and male
      offspring when adults; its relation to median eminence TRH, serum thyrotropin,
      leptin and thyroid hormones concentration. Offspring ate the same diet as their
      dams (CC, DD) or were switched from dietary regime after weaning (CD, DC) and
      until 2.5 months of age. DD males showed decreased adenohypophyseal and medial
      basal-hypothalamic PPII activity, along with high thyrotropin serum
      concentration. Post-weaning Zn-deficiency (CD) decreased PPII activity only in
      adenohypophysis and increased thyrotropin circulating levels. Zn-replenishment
      (DC) normalized PPII activity in both regions and serum thyrotropin
      concentration. Adenohypophyseal PPII activity decreased and prolactin levels
      increased in Zn-deficient dams. We concluded that long-term changes in dietary Zn
      down-regulate PPII activity independently of T3, increasing thyrotropin serum
      concentration, overall resembling sub-clinical hypothyroidism. 

PMID- 26315401
TI  - Investigating client perception and attitude to decentralization of HIV/AIDS
      treatment services to primary health centres in three Nigerian states.
AB  - BACKGROUND: The opinions of consumers in decentralization provide insights into
      possible levels of improvement in access and uptake of services. OBJECTIVES: The
      study examined clients' perception and attitude towards decentralization of
      antiretroviral treatment services from central hospitals to primary health
      centres (PHCs). METHODOLOGY: A cross-sectional survey was undertaken in three
      states in Nigeria. A total of 1265 exit interviews were conducted with HIV/AIDS
      clients in nine health facilities. FINDINGS: About a third of all the respondents
      were not comfortable with receiving ART services in a PHC facility close to where
      they live. The reasons given by 385 respondents who would not want their
      treatment centres near were as follows: fear of disclosure, 299 (80.4%); fear of
      being discriminated against, 278 (74.3%); and satisfaction with care received at
      current facility, 278 (74.3%). However, more than 90% of respondents in all three
      states felt that decentralization of ART services to PHCs would be beneficial in
      controlling HIV/AIDS in Nigeria; the difference in respondents' perception across
      the three state was found to be statistically significant (P < 0.001).
      CONCLUSION: The findings imply that scaling-up of treatment services to PHCs
      would be widely accepted, and probably result in increased uptake. However, this
      must be accompanied by targeted behaviour change interventions for clients who
      for the fear of disclosure and stigma would still not access care from proximate
      facilities.

PMID- 26315402
TI  - Intraventricular hemorrhage in asphyxiated newborns treated with hypothermia: a
      look into incidence, timing and risk factors.
AB  - BACKGROUND: Intraventricular hemorrhage (IVH) is uncommon in term newborns.
      Asphyxia and hypothermia have been mentioned separately as possible risk factors
      of IVH, since they might cause fluctuations of cerebral blood flow. The aim of
      this study was to assess the incidence, the timing, and the risk factors of
      intraventricular hemorrhage (IVH) in term asphyxiated newborns treated with
      hypothermia. METHODS: We conducted a prospective cohort study of all term
      asphyxiated newborns treated with hypothermia from August 2008 to June 2013. The
      presence or not of IVH was assessed using brain magnetic resonance imaging (MRI)
      performed after the hypothermia treatment was completed or using head ultrasound
      during the hypothermia treatment. For these newborns, to determine the timing of
      IVH, we retrospectively reviewed if they had other brain imaging studies
      performed during their neonatal hospitalization stay. In addition, we compared
      their general characteristics with those not developing IVH. RESULTS: One hundred
      and sixty asphyxiated newborns met the criteria for hypothermia. Fifteen of these
      newborns developed IVH, leading to an estimate of 9% (95% CI: 5.3-15.0%) of IVH
      in this population of newborns. Fifty-three percent had hemorrhage limited to the
      choroid plexus or IVH without ventricular dilatation; 47% had IVH with
      ventricular dilatation or parenchymal hemorrhage. Sixty-seven percent had an
      initial normal brain imaging; the diagnostic brain imaging that demonstrated the
      IVH was obtained either during cooling (in 30%), within 24 h of the rewarming (in
      30%), or 24 h after the rewarming (in 40%). Recurrent seizures were the
      presenting symptom of IVH during the rewarming in 20% of the newborns.
      Coagulopathy was more frequent in the asphyxiated newborns developing IVH (p <
      0.001). The asphyxiated newborns developing IVH also presented more frequently
      with persistent pulmonary hypertension, hypotension, thrombocytopenia and
      coagulopathy (p = 0.03). CONCLUSIONS: The asphyxiated newborns treated with
      hypothermia appear to be at an increased risk of IVH, especially those with
      significant hemodynamic instability. IVH seems to develop during late hypothermia
      and rewarming. Efforts should be directed towards maintaining hemodynamic
      stability in these patients, even during the rewarming.

PMID- 26315403
TI  - Impairment of Macrophage Cholesterol Efflux by Cholesterol Hydroperoxide
      Trafficking: Implications for Atherogenesis Under Oxidative Stress.
AB  - OBJECTIVE: Oxidative stress associated with cardiovascular disease can produce
      various oxidized lipids, including cholesterol oxides, such as 7-hydroperoxide (7
      OOH), 7-hydroxide (7-OH), and 7-ketone (7=O). Unlike 7=O and 7-OH, 7-OOH is redox
      active, giving rise to the others via potentially toxic-free radical reactions.
      We tested the novel hypothesis that under oxidative stress conditions,
      steroidogenic acute regulatory (StAR) family proteins not only deliver
      cholesterol to/into mitochondria of vascular macrophages, but also 7-OOH, which
      induces peroxidative damage that impairs early stage reverse cholesterol
      transport. APPROACH AND RESULTS: Stimulation of human monocyte-derived THP-1
      macrophages with dibutyryl-cAMP resulted in substantial upregulation of StarD1
      and ATP-binding cassette (ABC) transporter, ABCA1. Small interfering RNA-induced
      StarD1 knockdown before stimulation had no effect on StarD4, but reduced ABCA1
      upregulation, linking the latter to StarD1 functionality. Mitochondria in
      stimulated StarD1-knockdown cells internalized 7-OOH slower than nonstimulated
      controls and underwent less 7-OOH-induced lipid peroxidation and membrane
      depolarization, as probed with C11-BODIPY (4,4-difluoro-5-(4-phenyl-1,3
      butadienyl)-4-bora-3a,4a-diaza-s-inda-cene-3-undecanoic acid) and JC-1 (5,5',6,6'
      tetrachloro-1,1',3,3'-tetraethyl-benzimidazolylcarbocyanine iodide),
      respectively. Major functional consequences of 7-OOH exposure were (1) loss of
      mitochondrial CYP27A1 activity, (2) reduced 27-hydroxycholesterol (27-OH) output,
      and (3) downregulation of cholesterol-exporting ABCA1 and ABCG1. Consistently, 7
      OOH-challenged macrophages exported less cholesterol to apoA-I or high-density
      lipoprotein than did nonchallenged controls. StarD1-mediated 7-OOH transport was
      also found to be highly cytotoxic, whereas 7=O and 7-OH were minimally toxic.
      CONCLUSIONS: This study describes a previously unrecognized mechanism by which
      macrophage cholesterol efflux can be incapacitated under oxidative stress-linked
      disorders, such as chronic obesity and hypertension. Our findings provide new
      insights into the role of macrophage redox damage/dysfunction in atherogenesis.

PMID- 26315404
TI  - Modulation of the Coagulation Cascade Using Aptamers.
AB  - As a novel class of therapeutics, aptamers, or nucleic acid ligands, have
      garnered clinical interest because of the ease of isolating a highly specific
      aptamer against a wide range of targets, their chemical flexibility and
      synthesis, and their inherent ability to have their function reversed. The
      following review details the development and molecular mechanisms of aptamers
      targeting specific proteases in the coagulation cascade. The ability of these
      anticoagulant aptamers to bind to and inhibit exosite function rather than
      binding within the active site highlights the importance of exosites in blocking
      protein function. As both exosite inhibitors and reversible agents, the use of
      aptamers is a promising strategy for future therapeutics. 

PMID- 26315405
TI  - XBP 1-Deficiency Abrogates Neointimal Lesion of Injured Vessels Via Cross Talk
      With the PDGF Signaling.
AB  - OBJECTIVE: Smooth muscle cell (SMC) migration and proliferation play an essential
      role in neointimal formation after vascular injury. In this study, we intended to
      investigate whether the X-box-binding protein 1 (XBP1) was involved in these
      processes. APPROACH AND RESULTS: In vivo studies on femoral artery injury models
      revealed that vascular injury triggered an immediate upregulation of XBP1
      expression and splicing in vascular SMCs and that XBP1 deficiency in SMCs
      significantly abrogated neointimal formation in the injured vessels. In vitro
      studies indicated that platelet-derived growth factor-BB triggered XBP1 splicing
      in SMCs via the interaction between platelet-derived growth factor receptor beta
      and the inositol-requiring enzyme 1alpha. The spliced XBP1 (XBP1s) increased SMC
      migration via PI3K/Akt activation and proliferation via downregulating calponin
      h1 (CNN1). XBP1s directed the transcription of mir-1274B that targeted CNN1 mRNA
      degradation. Proteomic analysis of culture media revealed that XBP1s decreased
      transforming growth factor (TGF)-beta family proteins secretion via
      transcriptional suppression. TGF-beta3 but not TGF-beta1 or TGF-beta2 attenuated
      XBP1s-induced CNN1 decrease and SMC proliferation. CONCLUSIONS: This study
      demonstrates for the first time that XBP1 is crucial for SMC proliferation via
      modulating the platelet-derived growth factor/TGF-beta pathways, leading to
      neointimal formation.

PMID- 26315406
TI  - Rho-Kinase Inhibition During Early Cardiac Development Causes Arrhythmogenic
      Right Ventricular Cardiomyopathy in Mice.
AB  - OBJECTIVE: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is
      characterized by fibrofatty changes of the right ventricle, ventricular
      arrhythmias, and sudden death. Though ARVC is currently regarded as a disease of
      the desmosome, desmosomal gene mutations have been identified only in half of
      ARVC patients, suggesting the involvement of other associated mechanisms. Rho
      kinase signaling is involved in the regulation of intracellular transport and
      organizes cytoskeletal filaments, which supports desmosomal protein complex at
      the myocardial cell-cell junctions. Here, we explored whether inhibition of Rho
      kinase signaling is involved in the pathogenesis of ARVC. APPROACH AND RESULTS:
      Using 2 novel mouse models with SM22alpha- or alphaMHC-restricted overexpression
      of dominant-negative Rho-kinase, we show that mice with Rho-kinase inhibition in
      the developing heart (SM22alpha-restricted) spontaneously develop cardiac
      dilatation and dysfunction, myocardial fibrofatty changes, and ventricular
      arrhythmias, resulting in premature sudden death, phenotypes fulfilling the
      criteria of ARVC in humans. Rho-kinase inhibition in the developing heart results
      in the development of ARVC phenotypes in dominant-negative Rho-kinase mice
      through 3 mechanisms: (1) reduction of cardiac cell proliferation and ventricular
      wall thickness, (2) stimulation of the expression of the proadipogenic
      noncanonical Wnt ligand, Wnt5b, and the major adipogenic transcription factor,
      PPARgamma (peroxisome proliferator activated receptor-gamma), and inhibition of
      Wnt/beta-catenin signaling, and (3) development of desmosomal abnormalities.
      These mechanisms lead to the development of cardiac dilatation and dysfunction,
      myocardial fibrofatty changes, and ventricular arrhythmias, ultimately resulting
      in sudden premature death in this ARVC mouse model. CONCLUSIONS: This study
      demonstrates a novel crucial role of Rho-kinase inhibition during cardiac
      development in the pathogenesis of ARVC in mice.

PMID- 26315407
TI  - Kinetic and Related Determinants of Plasma Triglyceride Concentration in
      Abdominal Obesity: Multicenter Tracer Kinetic Study.
AB  - OBJECTIVES: Patients with obesity and diabetes mellitus have increased risk of
      cardiovascular disease. A major cause is an atherogenic dyslipidemia related
      primarily to elevated plasma concentrations of triglyceride-rich lipoproteins.
      The aim of this study was to clarify determinants of plasma triglyceride
      concentration. We focused on factors that predict the kinetics of very-low
      density lipoprotein 1 (VLDL1) triglycerides. APPROACH AND RESULTS: A multicenter
      study using dual stable isotopes (deuterated leucine and glycerol) and
      multicompartmental modeling was performed to elucidate the kinetics of
      triglycerides and apoB in VLDL1 in 46 subjects with abdominal obesity and
      additional cardiometabolic risk factors. Results showed that plasma triglyceride
      concentrations were dependent on both the secretion rate (r=0.44, P<0.01; r=0.45,
      P<0.01) and fractional catabolism (r=0.49, P<0.001; r=0.55, P<0.001) of VLDL1
      triglycerides and VLDL1-apoB. Liver fat mass was independently and directly
      associated with secretion rates of VLDL1-triglycerides (r=0.56, P<0.001) and
      VLDL1-apoB (r=0.53, P<0.001). Plasma apoC-III concentration was independently and
      inversely associated with the fractional catabolisms of VLDL1-triglycerides
      (r=0.48, P<0.001) and VLDL1-apoB (r=0.51, P<0.001). CONCLUSIONS: Plasma
      triglyceride concentrations in abdominal obesity are determined by the kinetics
      of VLDL1 subspecies, catabolism being mainly dependent on apoC-III concentration
      and secretion on liver fat content. Reduction in liver fat and targeting apoC-III
      may be an effective approach for correcting triglyceride metabolism atherogenic
      dyslipidemia in obesity.

PMID- 26315409
TI  - Preparing for the next Katrina.

PMID- 26315408
TI  - Mitochondrial Aldehyde Dehydrogenase 2 Regulates Revascularization in Chronic
      Ischemia: Potential Impact on the Development of Coronary Collateral Circulation.
AB  - OBJECTIVE: Revascularization is an essential process to compensate for cardiac
      underperfusion and, therefore, preserves cardiac function in the face of chronic
      ischemic injury. Recent evidence suggested a vital role of aldehyde dehydrogenase
      2 (ALDH2) in cardiac protection after ischemia. This study was designed to
      determine whether ALDH2 regulates chronic ischemia-induced angiogenesis and to
      explore the underlying mechanism involved. Moreover, the clinical impact of the
      ALDH2 mutant allele on the development of coronary collateral circulation (CCC)
      was evaluated. APPROACH AND RESULTS: Mice limb ischemia was performed. Compared
      with wild-type, ALDH2 deletion significantly reduced perfusion recovery, small
      artery and capillary density, and increased muscle atrophy in this ischemic
      model. In vitro, ALDH2-knockdown reduced proliferation, migration and hypoxia
      triggered endothelial tube formation of endothelial cells, the effects of which
      were restored by ALDH2 transfection. Further examination revealed that ALDH2
      regulated angiogenesis possibly through hypoxia-inducible factor-1alpha/vascular
      endothelial growth factor pathways. To further discern the role of ALDH2
      deficiency in the function of bone marrow stem/progenitor cells, cross bone
      marrow transplantation was performed between wild-type and ALDH2-knockout mice.
      However, there was no significant improvement for wild-type bone marrow
      transplantation into knockout mice. ALDH2 genotyping was screened in 139 patients
      with chronic total occlusion recruited to Zhongshan Hospital (2011.10-2014.4).
      Patients with poor CCC (Rentrop 0-1; n=51) exhibited a higher frequency of the AA
      genotype than those with enriched CCC (Rentrop 2-3; n=88; 11.76% versus 1.14%;
      P=0 0.01). However, the AA group displayed less enriched CCC frequency in
      Logistic regression model when compared with the GG group (odds ratio=0.08; 95%
      confidence interval, 0.009-0.701; P=0 0.026). Furthermore, serum vascular
      endothelial growth factor level tended to be lower in patients with ALDH2
      mutation. CONCLUSIONS: This study demonstrated that ALDH2 possesses an intrinsic
      capacity to regulate angiogenesis via hypoxia-inducible factor-1alpha and
      vascular endothelial growth factor. Patients with ALDH2-deficient genotype
      displayed a higher risk of developing poor CCC. Therapeutic individualization
      based on ALDH2 allele distribution may thus improve the therapeutic benefit,
      especially in the East Asian decedents.

PMID- 26315411
TI  - BRAZIL. Fiscal crisis has Brazilian scientists scrambling.

PMID- 26315412
TI  - REPRODUCIBILITY. Many psychology papers fail replication test.

PMID- 26315413
TI  - NEUROSCIENCE. Plugged pores may underlie some ALS, dementia cases.

PMID- 26315414
TI  - ENERGY. Dark horse scores a fusion coup.

PMID- 26315415
TI  - BOTANY. Orchids' dazzling diversity explained.

PMID- 26315416
TI  - The missing mudbug.

PMID- 26315417
TI  - Birth of the moralizing gods.

PMID- 26315418
TI  - Turning history into a binary code.

PMID- 26315419
TI  - SYNTHETIC BIOLOGY. Synthetic communities, the sum of parts.

PMID- 26315420
TI  - ORGANIC CHEMISTRY. As simple as [2+2].

PMID- 26315422
TI  - ANTHROPOLOGY. Defining the genus Homo.

PMID- 26315421
TI  - MICROBIOME. Microbiota RORgulates intestinal suppressor T cells.

PMID- 26315423
TI  - Gene editing: Advising advice.

PMID- 26315424
TI  - The wisdom of baboon decisions.

PMID- 26315425
TI  - The wisdom of baboon decisions-Response.

PMID- 26315426
TI  - BIOPHYSICS. Comment on "Extreme electric fields power catalysis in the active
      site of ketosteroid isomerase".
AB  - Fried et al. (Reports, 19 December 2014, p. 1510) demonstrated a strong
      correlation between reaction rate and the carbonyl stretching frequency of a
      product analog bound to ketosteroid isomerase oxyanion hole mutants and concluded
      that the active-site electric field provides 70% of catalysis. Alternative
      comparisons suggest a smaller contribution, relative to the corresponding
      solution reaction, and highlight the importance of atomic-level descriptions. 

PMID- 26315427
TI  - BIOPHYSICS. Comment on "Extreme electric fields power catalysis in the active
      site of ketosteroid isomerase".
AB  - Fried et al. (Reports, 19 December 2014, p. 1510) demonstrate electric field
      dependent acceleration of biological catalysis using ketosteroid isomerase as a
      prototypic example. These findings were not extended to aqueous solution because
      water by itself has field fluctuations that are too large and fast to provide a
      catalytic effect. Given physiological context, when water electrostatic
      interactions are considered, electric fields play a less important role in the
      catalysis. 

PMID- 26315428
TI  - BIOPHYSICS. Response to Comments on "Extreme electric fields power catalysis in
      the active site of ketosteroid isomerase".
AB  - Natarajan et al. and Chen and Savidge comment that comparing the electric field
      in ketosteroid isomerase's (KSI's) active site to zero overestimates the
      catalytic effect of KSI's electric field because the reference reaction occurs in
      water, which itself exerts a sizable electrostatic field. To compensate,
      Natarajan et al. argue that additional catalytic weight arises from positioning
      of the general base, whereas Chen and Savidge propose a separate contribution
      from desolvation of the general base. We note that the former claim is not well
      supported by published results, and the latter claim is intriguing but lacks
      experimental basis. We also take the opportunity to clarify some of the more
      conceptually subtle aspects of electrostatic catalysis. 

PMID- 26315429
TI  - FUNGAL BIOGEOGRAPHY. Response to Comment on "Global diversity and geography of
      soil fungi".
AB  - Schadt and Rosling (Technical Comment, 26 June 2015, p. 1438) argue that primer
      template mismatches neglected the fungal class Archaeorhizomycetes in a global
      soil survey. Amplicon-based metabarcoding of nine barcode-primer pair
      combinations and polymerase chain reaction (PCR)-free shotgun metagenomics
      revealed that barcode and primer choice and PCR bias drive the diversity and
      composition of microorganisms in general, but the Archaeorhizomycetes were little
      affected in the global study. We urge that careful choice of DNA markers and
      primers is essential for ecological studies using high-throughput sequencing for
      identification. 

PMID- 26315430
TI  - SOLID-STATE PHYSICS. Scalable T2 resistivity in a small single-component Fermi
      surface.
AB  - Scattering among electrons generates a distinct contribution to electrical
      resistivity that follows a quadratic temperature (T) dependence. In strongly
      correlated electron systems, the prefactor A of this T(2) resistivity scales with
      the magnitude of the electronic specific heat, gamma. Here we show that one can
      change the magnitude of A by four orders of magnitude in metallic strontium
      titanate (SrTiO3) by tuning the concentration of the carriers and, consequently,
      the Fermi energy. The T(2) behavior persists in the single-band dilute limit
      despite the absence of two known mechanisms for T(2) behavior: distinct electron
      reservoirs and Umklapp processes. The results highlight the absence of a
      microscopic theory for momentum decay through electron-electron scattering in
      various Fermi liquids. 

PMID- 26315431
TI  - QUANTUM MECHANICS. Quantum squeezing of motion in a mechanical resonator.
AB  - According to quantum mechanics, a harmonic oscillator can never be completely at
      rest. Even in the ground state, its position will always have fluctuations,
      called the zero-point motion. Although the zero-point fluctuations are
      unavoidable, they can be manipulated. Using microwave frequency radiation
      pressure, we have manipulated the thermal fluctuations of a micrometer-scale
      mechanical resonator to produce a stationary quadrature-squeezed state with a
      minimum variance of 0.80 times that of the ground state. We also performed phase
      sensitive, back-action evading measurements of a thermal state squeezed to 1.09
      times the zero-point level. Our results are relevant to the quantum engineering
      of states of matter at large length scales, the study of decoherence of large
      quantum systems, and for the realization of ultrasensitive sensing of force and
      motion. 

PMID- 26315432
TI  - NANOPARTICLES. Production of amorphous nanoparticles by supersonic spray-drying
      with a microfluidic nebulator.
AB  - Amorphous nanoparticles (a-NPs) have physicochemical properties distinctly
      different from those of the corresponding bulk crystals; for example, their
      solubility is much higher. However, many materials have a high propensity to
      crystallize and are difficult to formulate in an amorphous structure without
      stabilizers. We fabricated a microfluidic nebulator that can produce amorphous
      NPs from a wide range of materials, even including pure table salt (NaCl). By
      using supersonic air flow, the nebulator produces drops that are so small that
      they dry before crystal nuclei can form. The small size of the resulting spray
      dried a-NPs limits the probability of crystal nucleation in any given particle
      during storage. The kinetic stability of the a-NPs-on the order of months-is
      advantageous for hydrophobic drug molecules.

PMID- 26315433
TI  - ORGANIC CHEMISTRY. Iron-catalyzed intermolecular [2+2] cycloadditions of
      unactivated alkenes.
AB  - Cycloadditions, such as the [4+2] Diels-Alder reaction to form six-membered
      rings, are among the most powerful and widely used methods in synthetic
      chemistry. The analogous [2+2] alkene cycloaddition to synthesize cyclobutanes is
      kinetically accessible by photochemical methods, but the substrate scope and
      functional group tolerance are limited. Here, we report iron-catalyzed
      intermolecular [2+2] cycloaddition of unactivated alkenes and cross cycloaddition
      of alkenes and dienes as regio- and stereoselective routes to cyclobutanes.
      Through rational ligand design, development of this base metal-catalyzed method
      expands the chemical space accessible from abundant hydrocarbon feedstocks. 

PMID- 26315434
TI  - SEXUAL SELECTION. Irrationality in mate choice revealed by tungara frogs.
AB  - Mate choice models derive from traditional microeconomic decision theory and
      assume that individuals maximize their Darwinian fitness by making economically
      rational decisions. Rational choices exhibit regularity, whereby the relative
      strength of preferences between options remains stable when additional options
      are presented. We tested female frogs with three simulated males who differed in
      relative call attractiveness and call rate. In binary choice tests, females'
      preferences favored stimulus caller B over caller A; however, with the addition
      of an inferior "decoy" C, females reversed their preferences and chose A over B.
      These results show that the relative valuation of mates is not independent of
      inferior alternatives in the choice set and therefore cannot be explained with
      the rational choice models currently used in sexual selection theory. 

PMID- 26315435
TI  - LIFE HISTORY. Age-related mortality explains life history strategies of tropical
      and temperate songbirds.
AB  - Life history theory attempts to explain why species differ in offspring number
      and quality, growth rate, and parental effort. I show that unappreciated
      interactions of these traits in response to age-related mortality risk challenge
      traditional perspectives and explain life history evolution in songbirds. Counter
      to a long-standing paradigm, tropical songbirds grow at similar overall rates to
      temperate species but grow wings relatively faster. These growth tactics are
      favored by predation risk, both in and after leaving the nest, and are
      facilitated by greater provisioning of individual offspring by parents. Increased
      provisioning of individual offspring depends on partitioning effort among fewer
      young because of constraints on effort from adult and nest mortality. These
      growth and provisioning responses to mortality risk finally explain the conundrum
      of small clutch sizes of tropical birds. 

PMID- 26315436
TI  - FUNGAL SYMBIONTS. Global assessment of arbuscular mycorrhizal fungus diversity
      reveals very low endemism.
AB  - The global biogeography of microorganisms remains largely unknown, in contrast to
      the well-studied diversity patterns of macroorganisms. We used arbuscular
      mycorrhizal (AM) fungus DNA from 1014 plant-root samples collected worldwide to
      determine the global distribution of these plant symbionts. We found that AM
      fungal communities reflected local environmental conditions and the spatial
      distance between sites. However, despite AM fungi apparently possessing limited
      dispersal ability, we found 93% of taxa on multiple continents and 34% on all six
      continents surveyed. This contrasts with the high spatial turnover of other
      fungal taxa and with the endemism displayed by plants at the global scale. We
      suggest that the biogeography of AM fungi is driven by unexpectedly efficient
      dispersal, probably via both abiotic and biotic vectors, including humans. 

PMID- 26315437
TI  - NEURONAL DEVELOPMENT. Glycerophospholipid regulation of modality-specific sensory
      axon guidance in the spinal cord.
AB  - Glycerophospholipids, the structural components of cell membranes, have not been
      considered to be spatial cues for intercellular signaling because of their
      ubiquitous distribution. We identified lyso-phosphatidyl-beta-D-glucoside
      (LysoPtdGlc), a hydrophilic glycerophospholipid, and demonstrated its role in
      modality-specific repulsive guidance of spinal cord sensory axons. LysoPtdGlc is
      locally synthesized and released by radial glia in a patterned spatial
      distribution to regulate the targeting of nociceptive but not proprioceptive
      central axon projections. Library screening identified the G protein-coupled
      receptor GPR55 as a high-affinity receptor for LysoPtdGlc, and GPR55 deletion or
      LysoPtdGlc loss of function in vivo caused the misallocation of nociceptive axons
      into proprioceptive zones. These findings show that LysoPtdGlc/GPR55 is a lipid
      based signaling system in glia-neuron communication for neural development.

PMID- 26315438
TI  - DNA RECOMBINATION. Base triplet stepping by the Rad51/RecA family of
      recombinases.
AB  - DNA strand exchange plays a central role in genetic recombination across all
      kingdoms of life, but the physical basis for these reactions remains poorly
      defined. Using single-molecule imaging, we found that bacterial RecA and
      eukaryotic Rad51 and Dmc1 all stabilize strand exchange intermediates in precise
      three-nucleotide steps. Each step coincides with an energetic signature (0.3 kBT)
      that is conserved from bacteria to humans. Triplet recognition is strictly
      dependent on correct Watson-Crick pairing. Rad51, RecA, and Dmc1 can all step
      over mismatches, but only Dmc1 can stabilize mismatched triplets. This finding
      provides insight into why eukaryotes have evolved a meiosis-specific recombinase.
      We propose that canonical Watson-Crick base triplets serve as the fundamental
      unit of pairing interactions during DNA recombination. 

PMID- 26315439
TI  - HEART DISEASE. Titin mutations in iPS cells define sarcomere insufficiency as a
      cause of dilated cardiomyopathy.
AB  - Human mutations that truncate the massive sarcomere protein titin [TTN-truncating
      variants (TTNtvs)] are the most common genetic cause for dilated cardiomyopathy
      (DCM), a major cause of heart failure and premature death. Here we show that
      cardiac microtissues engineered from human induced pluripotent stem (iPS) cells
      are a powerful system for evaluating the pathogenicity of titin gene variants. We
      found that certain missense mutations, like TTNtvs, diminish contractile
      performance and are pathogenic. By combining functional analyses with RNA
      sequencing, we explain why truncations in the A-band domain of TTN cause DCM,
      whereas truncations in the I band are better tolerated. Finally, we demonstrate
      that mutant titin protein in iPS cell-derived cardiomyocytes results in sarcomere
      insufficiency, impaired responses to mechanical and beta-adrenergic stress, and
      attenuated growth factor and cell signaling activation. Our findings indicate
      that titin mutations cause DCM by disrupting critical linkages between
      sarcomerogenesis and adaptive remodeling. 

PMID- 26315440
TI  - SYNTHETIC BIOLOGY. Emergent genetic oscillations in a synthetic microbial
      consortium.
AB  - A challenge of synthetic biology is the creation of cooperative microbial systems
      that exhibit population-level behaviors. Such systems use cellular signaling
      mechanisms to regulate gene expression across multiple cell types. We describe
      the construction of a synthetic microbial consortium consisting of two distinct
      cell types-an "activator" strain and a "repressor" strain. These strains produced
      two orthogonal cell-signaling molecules that regulate gene expression within a
      synthetic circuit spanning both strains. The two strains generated emergent,
      population-level oscillations only when cultured together. Certain network
      topologies of the two-strain circuit were better at maintaining robust
      oscillations than others. The ability to program population-level dynamics
      through the genetic engineering of multiple cooperative strains points the way
      toward engineering complex synthetic tissues and organs with multiple cell types.

PMID- 26315441
TI  - The fungi that ate my house.

PMID- 26315442
TI  - ADVANCED IMAGING. Extended-resolution structured illumination imaging of
      endocytic and cytoskeletal dynamics.
AB  - Super-resolution fluorescence microscopy is distinct among nanoscale imaging
      tools in its ability to image protein dynamics in living cells. Structured
      illumination microscopy (SIM) stands out in this regard because of its high speed
      and low illumination intensities, but typically offers only a twofold resolution
      gain. We extended the resolution of live-cell SIM through two approaches:
      ultrahigh numerical aperture SIM at 84-nanometer lateral resolution for more than
      100 multicolor frames, and nonlinear SIM with patterned activation at 45- to 62
      nanometer resolution for approximately 20 to 40 frames. We applied these
      approaches to image dynamics near the plasma membrane of spatially resolved
      assemblies of clathrin and caveolin, Rab5a in early endosomes, and alpha-actinin,
      often in relationship to cortical actin. In addition, we examined mitochondria,
      actin, and the Golgi apparatus dynamics in three dimensions. 

PMID- 26315444
TI  - COLLOIDS. Colloidal matter: Packing, geometry, and entropy.
AB  - Colloidal particles with well-controlled shapes and interactions are an ideal
      experimental system for exploring how matter organizes itself. Like atoms and
      molecules, these particles form bulk phases such as liquids and crystals. But
      they are more than just crude analogs of atoms; they are a form of matter in
      their own right, with complex and interesting collective behavior not seen at the
      atomic scale. Their behavior is affected by geometrical or topological
      constraints, such as curved surfaces or the shapes of the particles. Because the
      interactions between the particles are often short-ranged, we can understand the
      effects of these constraints using geometrical concepts such as packing. The
      geometrical viewpoint gives us a window into how entropy affects not only the
      structure of matter, but also the dynamics of how it forms. 

PMID- 26315446
TI  - Mitoprotective dietary approaches for Myalgic Encephalomyelitis/Chronic Fatigue
      Syndrome: Caloric restriction, fasting, and ketogenic diets.
AB  - Myalgic Encephalomyelitis/Chronic Fatigue Syndrome is an idiopathic illness
      characterized by debilitating fatigue and neuro-immune abnormalities. A growing
      body of evidence proposes mitochondrial dysfunction as a central perpetrator of
      the illness due to activation of immune-inflammatory pathways that burden the
      mitochondria. Under a model of mitochondrial dysfunction, this paper explores
      dietary strategies that are mitoprotective. Studied for decades, the cellular
      mechanisms of ketogenic diets, fasting, and caloric restriction now reveal
      mitochondria-specific mechanisms which could play a role in symptom reduction in
      Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Future research should
      examine the physiological effects of these dietary strategies in Myalgic
      Encephalomyelitis/Chronic Fatigue Syndrome. 

PMID- 26315445
TI  - One-year trajectories of mental and physical functioning during and after
      rehabilitation among individuals with disabilities.
AB  - PURPOSE: First, to evaluate the trajectories of physical and mental functioning
      in individuals with chronic disabilities receiving adapted physical activity
      based rehabilitation. Second, to determine whether demographic factors,
      disability group, pain, fatigue and self-efficacy at baseline influenced these
      trajectories. RESEARCH DESIGN: A prospective intervention study. METHODS: The
      study included 214 subjects with chronic disabilities who were admitted to a four
      week adapted physical activity-based rehabilitation stay at Beitostolen
      Healthsports Centre. The subjects completed written questionnaires eight and four
      weeks before the rehabilitation, at admission to and discharge from the
      rehabilitation centre and again four weeks and 12 months after discharge.
      Multilevel models were performed to examine the trajectories of SF-12 physical
      and mental functioning with possible predictors. RESULTS: Time yielded a
      statistically significant effect on physical and mental functioning (p < 0.001).
      Low age (p = 0.002), no more than 2 h of personal assistance per week (p =
      0.023), non-nervous system disability (p = 0.019), low pain level (p < 0.001) and
      high chronic disease-efficacy (p = 0.007) were associated with higher physical
      functioning. There was a greater improvement in physical functioning for subjects
      with lower chronic disease-efficacy at baseline (p = 0.036) and with a disability
      not associated with the nervous system (p = 0.040). Low fatigue (p = 0.001) and
      high chronic disease-efficacy (p = 0.004) predicted higher mental functioning.
      There was also a greater improvement in mental functioning for subjects with high
      fatigue (p =0.003) and low chronic disease efficacy at baseline (p = 0.032).
      CONCLUSION: Individuals with chronic disabilities who participated in an adapted
      physical activity-based intervention showed statistically significant increases
      in both physical and mental functioning across the 12 months after the
      intervention. The greatest improvement was among subjects with a high level of
      fatigue and low chronic disease-efficacy, as well as disabilities not associated
      with the nervous system, which has implications for the target groups in future
      rehabilitation.

PMID- 26315447
TI  - Noise sensitivity: A neurophenomenological perspective.
AB  - This paper addresses the current limitations of noise sensitivity research and
      the benefit of undertaking a neurophenomenological approach of investigation. It
      begins by questioning the invariance of noise sensitivity across different
      studies and contexts and argues that these are issues associated with the
      psychometric construct rather than the underlying reaction patterns. It suggest
      that our definition and operationalization of noise sensitivity might have been
      misspecified and that it needs to be revised on the basis of heuristically
      derived first-person data about our experiences of noise. It then shows why the
      basic principles of the neurophenomenological program are applicable to
      psychoacoustic research. Namely, it argues that phenomenological training leading
      to reflexive introspection and verbalization of our susceptibility to noise might
      have three-fold implication - (i) it will generate deeper understanding of noise
      sensitivity which will then allow us to deduce a hierarchical structure of
      meaning and concepts to supplement and be fed to quantitative research, (ii) it
      will provide better interpretation of neuroimaging and electroencephalographic
      data related to noise reaction and perception, which in turn will allow a process
      of reciprocal validation, (iii) and, most importantly, it presents a promising
      technique for emotional regulation of noise processing via modulation of the
      amygdalar function, when a state of awareness of this processing has been
      achieved. 

PMID- 26315448
TI  - Retinal layer location of increased retinal thickness in eyes with subclinical
      and clinical macular edema in diabetes type 2.
AB  - PURPOSE: To identify the retinal layer predominantly affected in eyes with
      subclinical and clinical macular edema in diabetes type 2. METHODS: A cohort of
      194 type 2 diabetic eyes/patients with mild nonproliferative diabetic retinopathy
      (ETDRS levels 20/35) were examined with Cirrus spectral-domain optical coherence
      tomography (OCT) at the baseline visit (ClinicalTrials.gov identifier:
      NCT01145599). Automated segmentation of the retinal layers of the eyes with
      subclinical and clinical macular edema was compared with a sample of 31 eyes from
      diabetic patients with normal OCT and an age-matched control group of 58 healthy
      eyes. RESULTS: From the 194 eyes in the study, 62 had subclinical macular edema
      and 12 had clinical macular edema. The highest increases in retinal thickness
      (RT) were found in the inner nuclear layer (INL; 33.6% in subclinical macular
      edema and 81.8% in clinical macular edema). Increases were also found in the
      neighboring layers. Thinning of the retina was registered in the retinal nerve
      fiber, ganglion cells and inner plexiform layers in the diabetic eyes without
      macular edema. CONCLUSIONS: The increase in RT occurring in diabetic eyes with
      macular edema is predominantly located in the INL but extends to neighboring
      retinal layers indicating that it may be due to extracellular fluid accumulation.

PMID- 26315443
TI  - PSYCHOLOGY. Estimating the reproducibility of psychological science.
AB  - Reproducibility is a defining feature of science, but the extent to which it
      characterizes current research is unknown. We conducted replications of 100
      experimental and correlational studies published in three psychology journals
      using high-powered designs and original materials when available. Replication
      effects were half the magnitude of original effects, representing a substantial
      decline. Ninety-seven percent of original studies had statistically significant
      results. Thirty-six percent of replications had statistically significant
      results; 47% of original effect sizes were in the 95% confidence interval of the
      replication effect size; 39% of effects were subjectively rated to have
      replicated the original result; and if no bias in original results is assumed,
      combining original and replication results left 68% with statistically
      significant effects. Correlational tests suggest that replication success was
      better predicted by the strength of original evidence than by characteristics of
      the original and replication teams. 

PMID- 26315449
TI  - Microarray profiling of preselected CHO host cell subclones identifies gene
      expression patterns associated with increased production capacity.
AB  - Over the last three decades, product yields from CHO cells have increased
      dramatically, yet specific productivity (qP) remains a limiting factor. In a
      previous study, using repeated cell-sorting, we have established different host
      cell subclones that show superior transient qP over their respective parental
      cell lines (CHO-K1, CHO-S). The transcriptome of the resulting six cell lines in
      different biological states (untransfected, mock transfected, plasmid
      transfected) was first explored by hierarchical clustering and indicated that
      gene activity associated with increased qP did not stem from a certain cellular
      state but seemed to be inherent for a high qP host line. We then performed a
      novel gene regression analysis identifying drivers for an increase in qP. Genes
      significantly implicated were first systematically tested for enrichment of GO
      terms using a Bayesian approach incorporating the hierarchical structure of the
      GO term tree. Results indicated that specific cellular components such as
      nucleus, ER, and Golgi are relevant for cellular productivity. This was
      complemented by targeted GSA that tested functionally homogeneous, manually
      curated subsets of KEGG pathways known to be involved in transcription,
      translation, and protein processing. Significantly implicated pathways included
      mRNA surveillance, proteasome, protein processing in the ER and SNARE
      interactions in vesicular transport. 

PMID- 26315450
TI  - A homogeneous time-resolved fluorescence-based high-throughput screening for
      discovery of inhibitors of Nef-sdAb19 interaction.
AB  - The human immunodeficiency virus (HIV) protein negative factor (Nef) is important
      for AIDS pathogenesis. An anti-Nef single-domain antibody (sdAb19) derived from
      camelids has been previously generated and shown to effectively block the
      physiological functions of Nef in vitro and in vivo in nef-transgenic mice.
      However, sdAb19 must be ectopically expressed within the target cell to be able
      to exert its neutralizing effect on Nef, while the extra-cellular administration
      method turned out to be ineffective. This might suggest a default of the
      stability or/and deliverability of sdAb19. The identification of small molecule
      compounds capable of inhibiting the Nef-sdAb19 interaction and mimicking the
      neutralizing activity of sdAb19 in vivo would therefore be the means of
      circumventing the problem encountered with sdAb19. Here we describe the
      development of a high-throughput screening method combining the homogeneous time
      resolved fluorescence (HTRF) and the microscale thermophoresis (MST) techniques
      for the identification of small-molecule compounds inhibiting the Nef-sdAb19
      interaction by binding to Nef protein. Eight small-molecule compounds have been
      selected for their ability to significantly inhibit the Nef-sdAb19 interaction
      and to bind to Nef. These molecules could be further assessed for their potential
      of being the Nef-neutralizing agents in the future.

PMID- 26315451
TI  - Prevalence and clinical impact of fibromyalgia in patients with primary Sjogren's
      syndrome.
AB  - OBJECTIVES: Clinical features of primary Sjogren's syndrome (pSS) overlap with
      those of fibromyalgia (FM). This cross-sectional study was conducted to
      investigate the prevalence of FM in pSS patients and to compare the clinical
      features of pSS patients with FM to those without FM. METHODS: One hundred pSS
      patients were consecutively assessed to identify the presence of FM according to
      the American College of Rheumatology (ACR) 2010 criteria. Clinical and laboratory
      data were collected from all patients. Additional assessments included EULAR
      Sjogren's Syndrome Patient Reported Index (ESSPRI) and EULAR Sjogren's Syndrome
      Disease Activity Index (ESSDAI). The severity of depression was measured by
      Hamilton depression rating scale 17-items (HAM-D scale). RESULTS: The prevalence
      of FM was 31.0% (31/100) in pSS. Widespread pain index and symptom severity scale
      were significantly correlated with ESSPRI (r=0.6542 and r=0.7173, both p<0.0001)
      and HAM-D scale (r=0.6734 and r=0.6471, both p<0.0001) in pSS. In multivariate
      analysis, ESSPRI and HAM-D scale were independently associated with increase of
      tender point count and symptom severity scale. ESSPRI was significantly higher in
      pSS patients with FM compared to those without FM (p<0.0001). The prevalence of
      FM in pSS patients with moderate-to-severe depression was significantly higher
      than those with mild depression or without depression (odds ratio= 10.62,
      p=0.0009). Serum 25-hydroxy vitamin D3 levels in pSS patients with FM were
      significantly (p=0.0072) decreased compared to those without FM. CONCLUSIONS: Our
      study showed that FM was prevalent in pSS. FM was associated with higher ESSPRI
      and more severe depression.

PMID- 26315452
TI  - Dipolar motions and ionic conduction in an ibuprofen derived ionic liquid.
AB  - It was demonstrated that the combination of the almost water insoluble active
      pharmaceutical ingredient (API) ibuprofen with the biocompatible 1-ethanol-3
      methylimidazolium [C2OHMIM] cation of an ionic liquid (IL) leads to a highly
      water miscible IL-API with a solubility increased by around 5 orders of
      magnitude. Its phase transformations, as crystallization and glass transition,
      are highly sensitive to the water content, the latter shifting to higher
      temperatures upon dehydration. By dielectric relaxation spectroscopy the
      dynamical behavior of anhydrous [C2OHMIM][Ibu] and with 18.5 and 3% of water
      content (w/w) was probed from well below the calorimetric glass transition (Tg)
      up to the liquid state. Multiple reorientational dipolar processes were detected
      which become strongly affected by conductivity and electrode polarization near
      above Tg. Therefore [C2OHMIM][Ibu] exhibits mixed behavior of a conventional
      molecular glass former and an ionic conductor being analysed in this work through
      conductivity, electrical modulus and complex permittivity. The dominant process,
      sigmaalpha-process, originates by a coupling between both charge transport and
      dipolar mechanisms. The structural relaxation times were derived from
      permittivity analysis and confirmed by temperature modulated differential
      scanning calorimetry. The temperature dependence of the beta-secondary relaxation
      is coherent with a Johari-Goldstein (betaJG) process as detected in conventional
      glass formers. 

PMID- 26315453
TI  - Biomimetic Total Syntheses of (-)-Leucoridines A and C through the Dimerization
      of (-)-Dihydrovalparicine.
AB  - Concise biomimetic syntheses of the Strychnos-Strychnos-type bis-indole alkaloids
      (-)-leucoridine A (1) and C (2) were accomplished through the biomimetic
      dimerization of (-)-dihydrovalparicine (3). En route to 3, the known alkaloids
      (+)-geissoschizoline (8) and (-)-dehydrogeissoschizoline (10) were also prepared.
      DFT calculations were employed to elucidate the mechanism, which favors a
      stepwise aza-Michael/spirocyclization sequence over the alternate hetero-Diels
      Alder cycloaddition reaction. 

PMID- 26315455
TI  - Sugar and health in South Africa: Potential challenges to leveraging policy
      change.
AB  - A growing body of evidence indicates that excessive sugar consumption is driving
      epidemics of obesity and related non-communicable diseases (NCDs) around the
      world. South Africa (SA), a major consumer of sugar, is also the third most obese
      country in Africa, and 40% of all deaths in the country result from NCDs. A
      number of fiscal, regulatory, and legislative levers could reduce sugar
      consumption in SA. This paper focuses on a sugar-sweetened beverage (SSB) tax.
      The purpose of the paper is to highlight the challenges that government might
      anticipate. Policies cannot be enacted in a vacuum and discussion is focused on
      the industrial, economic, and societal context. The affected industry actors have
      been part of the SA economy for over a century and remain influential. To deflect
      attention, the sugar industry can be expected either to advocate for self
      regulation or to promote public-private partnerships. This paper cautions against
      both approaches as evidence suggests that they will be ineffective in curbing the
      negative health impacts caused by excessive sugar consumption. In summary, policy
      needs to be introduced with a political strategy sensitive to the various
      interests at stake. In particular, the sugar industry can be expected to be
      resistant to the introduction of any type of tax on SSBs.

PMID- 26315454
TI  - Trends in treatment and survival for advanced laryngeal cancer: A 20-year
      population-based study in The Netherlands.
AB  - BACKGROUND: The purpose of this study was to determine time trends for primary
      treatment modalities in advanced laryngeal cancer, overall survival (OS), and
      laryngectomy-free interval (LFI) over the last 2 decades in The Netherlands.
      METHODS: We conducted an analysis of T3 to T4 laryngeal cancer data from 2
      combined national (population-based and pathology-based) cancer registries.
      RESULTS: A total of 2072 T3 cases (14.7%) and 1722 T4 cases (12.2%) were
      identified. Total laryngectomy as primary treatment modality decreased, whereas
      radiotherapy (RT) increased. For T3 disease, 5-year OS after primary total
      laryngectomy (+/- adjuvant RT), RT, and chemoradiotherapy (CRT) was 49%, 47%, and
      45%, respectively. For T4 disease, this was 48%, 34%, and 42% (overall p <
      .0001), respectively. Five-year LFI for T3 disease was 81% (RT) and 77% (CRT),
      and for T4 disease it was 81% and 87%, respectively. CONCLUSION: From 1991 to
      2010 total laryngectomy as primary treatment modality for advanced laryngeal
      cancer decreased and RT increased. T3 disease showed similar survival rates for
      all primary treatment modalities. For T4 disease, total laryngectomy (+ adjuvant
      RT) showed the best survival. (c) 2015 Wiley Periodicals, Inc. Head Neck 38:
      E1247-E1255, 2016.

PMID- 26315456
TI  - On the uncertainty propagation in multiscale modeling of cortical bone
      elasticity.

PMID- 26315457
TI  - Position effect modifying gene expression in a patient with ring chromosome 14.
AB  - The clinical phenotype of patients with ring chromosomes usually reflects the
      loss of genomic material during ring formation. However, phenotypic alterations
      can also be found in the presence of complete ring chromosomes, in which the
      breakage and rejoining in terminal regions of both chromosome arms result in no
      gene loss. Here, we present a patient with a ring chromosome 14 that lost nothing
      but the telomeres. Since he and other patients with a similar chromosome
      abnormality present certain abnormal characteristics, we investigated the gene
      expression of eight chromosome 14 genes to find out whether the configuration of
      the ring had changed it, possibly producing some of these clinical features. The
      expression of these eight genes was studied by quantitative real-time polymerase
      chain reaction (qPCR) in the patient and in seven controls matched for gender and
      age. Two of them were found to be downregulated in the patient compared to the
      controls, indicating that his phenotype might be related to alterations in the
      expression of genes located in the abnormal chromosome, even when the copy number
      is normal. Thus, the phenotypic alterations found in the presence of complete
      ring chromosomes may be related to changes in the chromatin architecture,
      bringing about a change of expression by position effect. These results may
      explain some of the characteristics presented by our patient.

PMID- 26315458
TI  - Altered source memory retrieval is associated with pathological doubt in
      obsessive-compulsive disorder.
AB  - Individuals with obsessive-compulsive disorder (OCD) often complain of doubt
      related to memory. As neuropsychological research has demonstrated that
      individuals with OCD tend to focus on details and miss the larger context, the
      construct of source (contextual) memory may be particularly relevant to memory
      complaints in OCD. Memory for object versus contextual information relies on
      partially distinct regions within the prefrontal cortex, parietal and medial
      temporal lobe, and may be differentially impacted by OCD. In the present study,
      we sought to test the hypothesis that individuals with OCD exhibit impaired
      source memory retrieval using a novel memory paradigm - The Memory for Rooms Test
      (MFRT) - a four-room memory task in which participants walk through four rooms
      and attempt to encode and remember objects. Demographically matched individuals
      with OCD and healthy controls studied objects in the context of four rooms, and
      then completed a memory retrieval test while undergoing functional magnetic
      resonance imaging (fMRI). While no differences were observed in source memory
      accuracy, individuals with OCD exhibited greater task related activation in the
      posterior cingulate cortex (PCC) relative to healthy controls during correct
      source memory retrieval. During correct object recognition, individuals with OCD
      failed to recruit the dorsolateral prefrontal(DLPFC)/premotor, left mPFC, and
      right parietal regions to the same extent as healthy controls. Our results
      suggest abnormal recruitment of frontal-parietal and PCC regions during source
      verses object memory retrieval in OCD. Within the OCD group, activation in the
      PCC and the premotor/DLPFC was associated with greater pathological doubt. This
      finding is consistent with the observation that OCD patients often experience
      extreme doubt, even when memory performance is intact. 

PMID- 26315459
TI  - TrkB in the hippocampus and nucleus accumbens differentially modulates depression
      like behavior in mice.
AB  - Brain-derived neurotrophic factor (BDNF) exerts antidepressant-like effects in
      the hippocampus and pro-depressant effects in the nucleus accumbens (NAc). It is
      thought that downstream signaling of the BDNF receptor TrkB mediates the effects
      of BDNF in these brain structures. Here, we evaluate how TrkB regulates affective
      behavior in the hippocampus and NAc. We overexpressed TrkB by electroporating a
      non-viral plasmid in the NAc or hippocampus in mice. Depression- and anxiety-like
      behaviors were evaluated in the sucrose test (anhedonia), the forced swim test
      (despair) and the elevated zero maze (anxiety). Targeted brain tissue was
      biochemically analyzed to identify molecular mechanisms responsible for the
      observed behavior. Overexpressing TrkB in the NAc increased the number of young
      neuronal cells and decreased despair and basal corticosterone levels. TrkB
      overexpression in the hippocampus increased astrocyte production and activation
      of the transcription factor CREB, yet without altering affective behavior. Our
      data suggest antidepressant effects of BDNF-TrkB in the NAc, which could not be
      explained by activation of the transcription factors CREB or beta-catenin. The
      effects TrkB has on depression-related behavior in different brain regions appear
      to critically depend on the targeted cell type. 

PMID- 26315460
TI  - Vitamin D deficiency and its association with fatigue and quality of life in
      advanced cancer patients under palliative care: A cross-sectional study.
AB  - BACKGROUND: A normal vitamin D status is required for bones and muscles to
      maintain their function and structure, but it also contributes to the functional
      integrity of other multiple physiologic systems in the body. AIM: To assess the
      relationship of Vitamin D deficiency with health-related quality-of-life issues,
      fatigue, and physical functioning in advanced cancer patients. DESIGN: This is a
      cross-sectional study. PATIENTS/SETTINGS: Adults under palliative care, having a
      locally advanced or metastatic or inoperable solid cancer. RESULTS: Among 30
      patients in palliative care with advanced solid cancer, 90% were vitamin D
      deficient. Serum Vitamin D concentration was positively correlated with patient
      reported absence of fatigue (s = 0.49), and physical and functional well-being (s
      = 0.44 and s = 0.41, respectively, p < 0.01). Fatigue was the symptom with the
      highest median impact on their lives and was the only one associated with serum
      vitamin D (p = 0.031), with lower fatigue in patients with vitamin D
      concentrations in the third tertile. There was no evidence of a direct
      association between health-related quality of life and vitamin D status.
      CONCLUSION: The 90% frequency of advanced cancer patients with vitamin D
      deficiency, together with the positive correlation of vitamin D status with the
      absence of fatigue and improved physical and functional well-being, points to
      vitamin D supplementation as a potential therapy to enhance the patient's quality
      of life.

PMID- 26315461
TI  - Contemporary frameless intracranial biopsy techniques: Might variation in safety
      and efficacy be expected?
AB  - BACKGROUND: Frameless stereotactic neuronavigation has proven to be a feasible
      technology to acquire brain biopsies with good accuracy and little morbidity and
      mortality. New systems are constantly introduced into the neurosurgical
      armamentarium, although few studies have actually evaluated and compared the
      diagnostic yield, morbidity, and mortality of various manufacturer's frameless
      neuronavigation systems. The present study reports our experience with brain
      biopsy procedures performed using both the Medtronic Stealth Treon(TM) Vertek(r)
      and BrainLAB(r) Varioguide frameless stereotactic brain biopsy systems. PATIENTS
      AND METHODS: All 247 consecutive biopsies from January 2008 until May 2013 were
      evaluated retrospectively. One hundred two biopsies each were performed using the
      Medtronic (2008-2009) and BrainLAB(r) system (2011-2013), respectively. The year
      2010 was considered a transition year, in which 43 biopsies were performed with
      either system. Patient demographics, perioperative characteristics, and
      histological diagnosis were reviewed, and a comparison was made between the two
      brain biopsy systems. RESULTS: The overall diagnostic yield was 94.6 %, i.e., 11
      biopsies were nondiagnostic, 5 (4.9 %) with the Medtronic and 6 (5.9 %) with the
      BrainLAB(r) system. No differences besides the operating time (108 vs 120 min)
      were found between the two biopsy methods. On average, 6.6 tissue samples were
      taken with either technique. Peri- and postoperative complications were seen in
      5.3 % and 12.9 %, consisting of three symptomatic hemorrhages (1.2 %). Biopsy
      related mortality occurred in 0.8 % of all biopsies. CONCLUSIONS: Regarding
      diagnostic yield, complication rate, and biopsy-related mortality, there seems to
      be no difference between the frameless biopsy technique from Medtronic and
      BrainLAB(r). In contemporary time, the neurosurgeon has many tools to choose
      from, all with a relatively fast learning curve and ever improving feasibility.
      Thus, the issue of choice involves not the results, but the familiarity, end-user
      friendliness, and overall comfort when operating the system.

PMID- 26315462
TI  - A small conserved motif supports polarity augmentation of Shigella flexneri IcsA.
AB  - The rod-shaped enteric intracellular pathogen Shigella flexneri and other
      Shigella species are the causative agents of bacillary dysentery. S. flexneri are
      able to spread within the epithelial lining of the gut, resulting in lesion
      formation, cramps and bloody stools. The outer membrane protein IcsA is essential
      for this spreading process. IcsA is the initiator of an actin-based form of
      motility whereby it allows the formation of a filamentous actin 'tail' at the
      bacterial pole. Importantly, IcsA is specifically positioned at the bacterial
      pole such that this process occurs asymmetrically. The mechanism of IcsA polarity
      is not completely understood, but it appears to be a multifactorial process
      involving factors intrinsic to IcsA and other regulating factors. In this study,
      we further investigated IcsA polarization by its intramolecular N-terminal and
      central polar-targeting (PT) regions (nPT and cPT regions, respectively). The
      results obtained support a role in polar localization for the cPT region and
      contend the role of the nPT region. We identified single IcsA residues that have
      measurable impacts on IcsA polarity augmentation, resulting in decreased S.
      flexneri sprading efficiency. Intriguingly, regions and residues involved in PT
      clustered around a highly conserved motif which may provide a functional scaffold
      for polarity-augmenting residues. How these results fit with the current model of
      IcsA polarity determination is discussed. 

PMID- 26315463
TI  - Pyruvate kinase deficiency and severe congenital hemolytic anemia in a double
      heterozygous patient with paternal transmission of an early germ-line de novo
      mutation.

PMID- 26315464
TI  - Protective Effects of Modeled Superoxide Dismutase Coordination Compound (MSODa)
      Against Ischemia/Reperfusion Injury in Rat Skeletal Muscle.
AB  - BACKGROUND/AIM: Ischemia/reperfusion (I/R) injury of skeletal muscles is common
      pathophysiology during surgeries and the superoxide dismutase (SOD) plays a
      critical role in this process. SOD-modeled coordination compound (MSODa) may
      simulate the protective effects as SOD. METHODS: Therefore, this study was
      designed to explore the protective effects and underlying mechanism of MSODa on
      malondialdehyde (MDA) and integrin-beta2 (CD11b/CD18) in plasma, myeloperoxidase
      (MPO) and intercellular cell adhesion molecule-1 (ICAM-1) in tissue, and
      morphological changes before and after I/R injury. The rat model of I/R in hind
      limb was established and randomly divided into sham, ischemia, I/R, I/R-treated
      with saline, SOD, and MSODa, respectively. RESULTS: These results showed that
      averaged values for MDA, MPO, CD11b/CD18, and ICAM-1 were significantly increased
      (P < 0.01 vs ischemia alone) in a time-dependent fashion along with marked tissue
      remodeling, such as abnormal arrangement of muscular fibers, interstitial edema,
      vasodilation with no-reflow, inflammatory cells adherent and infiltration,
      structural changes in mitochondrial, and decrease in glycogens as well. However,
      all parameter changes induced by I/R injury were reversed, at least partially, by
      MSODa and SOD treatments and intriguingly, the beneficial/protective effects of
      MSODa was superior to SOD with an early onset. CONCLUSION: This novel finding
      demonstrates that MSODa improves I/R injury of skeletal muscles due at least
      partially to inhibition of adherent molecule expression and reduction of oxygen
      free radical formation during I/R pathophysiological processes and this
      protective action of MSODa was superior to SOD, highlighting the bright future
      for MSODa in clinical management of tissue I/R injury.

PMID- 26315465
TI  - Developing a treatment summary and survivorship care plan responsive to African
      American breast cancer survivors.

PMID- 26315466
TI  - Functional outcome of tongue motions with selective hypoglossal nerve stimulation
      in patients with obstructive sleep apnea.
AB  - BACKGROUND: Selective upper airway stimulation of the hypoglossal nerve is a
      novel therapy option for obstructive sleep apnea. Different tongue motions were
      observed after surgery during active therapy. METHODS: We examined tongue motions
      in 14 patients (mean age 51 +/- 10 years) who received an implantation of an
      upper airway stimulation system (Inspire Medical Systems) from September 2013 to
      February 2014 in three different implantation centers in Germany after surgery.
      Sleep recording was performed preoperatively: 2 months (M02) and 6 months (M06)
      after surgery. RESULTS: There were three different tongue motions observed after
      surgery at 1 month (M01), M02, and M06 after surgery: bilateral protrusion (BP),
      right protrusion (RP), and mixed activation (MA). At M01: 10 BP, 2 RP, and 2 MA;
      at M02: 12 BP, 0 RP, and 2 MA; and at M06: 12 BP, 0 RP, and 2 MA could be
      detected. The average apnea-hypopnea index (AHI) was reduced from 32.5 +/- 14.2/h
      before surgery to 17.9 +/- 23.3/h at M02 and 14.1 +/- 19.8/h at M06. An increased
      reduction in AHI was found in BP and RP group (Baseline: 29.6 +/- 12.6/h; M02:
      12.06 +/- 14.1/h; M06: 9.7 +/- 12.6/h) compared to the MA group (Baseline 49.6 +/
      13.8/h; M02: 49.7 +/- 5.1/h; M06: 40.5 +/- 4.1/h). CONCLUSIONS: These findings
      suggest that the postoperative tongue motions in upper airway stimulation are
      associated with the therapy outcome. The stimulation electrode placement on the
      hypoglossal nerve for selective muscle recruitment may play a role in the
      mechanism of action.

PMID- 26315467
TI  - Erythrocyte sedimentation rate may help predict severity of obstructive sleep
      apnea.
AB  - PURPOSE: Previous studies have shown a relationship between obstructive sleep
      apnea (OSA) and erythrocyte sedimentation rate (ESR), a representative marker for
      inflammation. We aimed to elucidate the possible association between elevated ESR
      and OSA severity. METHODS: A total of 341 patients who visited a sleep center
      were retrospectively enrolled. Subjects underwent physical examination, overnight
      polysomnography (PSG), and blood sampling for ESR and high-sensitivity C-reactive
      protein (hs-CRP). We compared the ESR and hs-CRP level to OSA severity and
      measured their correlation with other PSG parameters. RESULTS: The ESR was
      significantly higher in patients with severe OSA (apnea-hypopnea index (AHI) >=
      30) than those with simple snoring (AHI < 5; P = 0.016), mild OSA (5 <= AHI < 15;
      P = 0.010), and moderate OSA (15 <= AHI < 30; P = 0.042). Similarly, the hs-CRP
      level in patients with severe OSA was significantly higher than that in patients
      with simple snoring (P = 0.006) and mild OSA (P = 0.013). Multivariate analysis
      also showed that elevated ESR was associated with moderate and severe OSA
      (adjusted OR = 2.231 (P = 0.048) and 2.606 (P = 0.002), respectively) after
      adjusting for sex, age, body mass index, smoking, hypertension, diabetes
      mellitus, and hyperlipidemia. However, elevated hs-CRP was not associated with
      the OSA severity. CONCLUSIONS: ESR more closely correlated with PSG parameters
      recorded during sleep hypoxic episodes than hs-CRP. Moreover, the ESR may be
      useful to predict the OSA severity because moderate and severe OSA were
      independently associated with an elevated ESR.

PMID- 26315468
TI  - Metal-Borohydride-Modified Zr(BH4 )4 ?8 NH3 : Low-Temperature Dehydrogenation
      Yielding Highly Pure Hydrogen.
AB  - Due to its high hydrogen density (14.8 wt %) and low dehydrogenation peak
      temperature (130  degrees C), Zr(BH4 )4 ?8 NH3 is considered to be one of the
      most promising hydrogen-storage materials. To further decrease its
      dehydrogenation temperature and suppress its ammonia release, a strategy of
      introducing LiBH4 and Mg(BH4 )2 was applied to this system. Zr(BH4 )4 ?8 NH3 -4
      LiBH4 and Zr(BH4 )4 ?8 NH3 -2 Mg(BH4 )2 composites showed main dehydrogenation
      peaks centered at 81 and 106  degrees C as well as high hydrogen purities of 99.3
      and 99.8 mol % H2 , respectively. Isothermal measurements showed that 6.6 wt %
      (within 60 min) and 5.5 wt % (within 360 min) of hydrogen were released at 100 
      degrees C from Zr(BH4 )4 ?8 NH3 -4 LiBH4 and Zr(BH4 )4 ?8 NH3 -2 Mg(BH4 )2 ,
      respectively. The lower dehydrogenation temperatures and improved hydrogen
      purities could be attributed to the formation of the diammoniate of diborane for
      Zr(BH4 )4 ?8 NH3 -4 LiBH4 , and the partial transfer of NH3 groups from Zr(BH4 )4
      ?8 NH3 to Mg(BH4 )2 for Zr(BH4 )4 ?8 NH3 -2 Mg(BH4 )2 , which result in balanced
      numbers of BH4 and NH3 groups and a more active H(delta+) ???(-delta) H
      interaction. These advanced dehydrogenation properties make these two composites
      promising candidates as hydrogen-storage materials.

PMID- 26315469
TI  - Selective Inhibition of Membrane Type 1 Matrix Metalloproteinase Abrogates
      Progression of Experimental Inflammatory Arthritis: Synergy With Tumor Necrosis
      Factor Blockade.
AB  - OBJECTIVE: In rheumatoid arthritis (RA), destruction of articular cartilage by
      the inflamed synovium is considered to be driven by increased activities of
      proteolytic enzymes, including matrix metalloproteinases (MMPs). The purpose of
      this study was to investigate the therapeutic potential of selective inhibition
      of membrane type 1 MMP (MT1-MMP) and its combination with tumor necrosis factor
      (TNF) blockage in mice with collagen-induced arthritis (CIA). METHODS: CIA was
      induced in DBA/1 mice by immunization with bovine type II collagen. From the
      onset of clinical arthritis, mice were treated with MT1-MMP selective inhibitory
      antibody DX-2400 and/or TNFR-Fc fusion protein. Disease progression was monitored
      daily, and serum, lymph nodes, and affected paws were collected at the end of the
      study for cytokine and histologic analyses. For in vitro analysis, bone marrow
      derived macrophages were stimulated with lipopolysaccharide for 24 hours in the
      presence of DX-2400 and/or TNFR-Fc to analyze cytokine production and phenotype.
      RESULTS: DX-2400 treatment significantly reduced cartilage degradation and
      disease progression in mice with CIA. Importantly, when combined with TNF
      blockade, DX-2400 acted synergistically, inducing long-term benefit. DX-2400 also
      inhibited the up-regulation of interleukin-12 (IL-12)/IL-23 p40 via polarization
      toward an M2 phenotype in bone marrow-derived macrophages. Increased production
      of IL-17 induced by anti-TNF, which correlated with an incomplete response to
      anti-TNF, was abrogated by combined treatment with DX-2400 in CIA. CONCLUSION:
      Targeting MT1-MMP provides a potential strategy for joint protection, and its
      combination with TNF blockade may be particularly beneficial in RA patients with
      an inadequate response to anti-TNF therapy.

PMID- 26315470
TI  - Induction of labor in breech presentations at term: a retrospective observational
      study.
AB  - OBJECTIVE: The aim of this study is to evaluate whether induction of breech
      delivery at term is feasible and safe for mother and child compared with
      spontaneous vaginal breech delivery. STUDY DESIGN: A total of 268 singleton term
      breech deliveries with an attempted vaginal delivery were identified in a single
      center retrospective observational study. Out of these, 73 cases had an induction
      of labor for various medical and obstetric reasons and were compared to 195
      spontaneous singleton breech deliveries. The main outcome measure was the mode of
      delivery. Secondary outcomes included maternal and neonatal morbidity and
      mortality. RESULTS: The vaginal delivery rate in the induction group was 64.4%
      compared with 80% in the spontaneous delivery group. No statistical differences
      were observed between the two delivery groups regarding neonatal and maternal
      morbidity and mortality. CONCLUSIONS: The vaginal delivery rate was significantly
      lower in induced than in spontaneous breech deliveries. The neonatal and maternal
      morbidity and mortality rates were similar implying that induction in breech
      delivery is an option and it is time for clinical reappraisal.

PMID- 26315471
TI  - Vitamin D and its relation with ionic calcium, parathyroid hormone, maternal and
      neonatal characteristics in pregnancy after roux-en-Y gastric bypass.
AB  - PURPOSE: The objective of this study was to evaluate vitamin D nutritional status
      and its relation with ionic calcium, parathyroid hormone (PTH), maternal
      anthropometry and perinatal outcomes in pregnant women who previously underwent
      Roux-en-Y gastric bypass (RYGB) surgery. METHODS: In a clinic specialized in
      obesity control located in the city of Rio de Janeiro (Brazil), the following
      information were collected for adult women who underwent RYGB before pregnancy:
      serum concentrations of vitamin D [25(OH)D], calcium and PTH per gestational
      trimester and data on maternal anthropometry, gestational intercurrences and
      perinatal outcomes. RESULTS: The present study included 46 post-RYGB pregnant
      women. The prevalence of pregnant women with deficiency (<=20 ng/mL) or
      insufficiency (>=21 and 29 ng/mL) of vitamin D was above 70% in all trimesters.
      The prevalence of calcium deficiency was 15.2% in the first and in the second
      trimesters and 20% in the third trimester, while the prevalence of excess PTH was
      19.6, 30.4 and 32.6% in the first, the second and the third trimesters,
      respectively. In the second and the third trimesters, a significant difference
      was observed between concentrations of 25(OH)D, and a negative correlation was
      observed between concentrations of calcium and PTH. Association of 25(OH)D with
      urinary tract infection (UTI) was found, but there was no association with
      calcium, PTH, maternal anthropometry, type of delivery and weight and gestational
      age at birth CONCLUSIONS: The post-RYGB pregnant women showed an elevated serum
      inadequacy (deficiency or insufficiency) of 25(OH)D during pregnancy. Maternal
      vitamin D status showed no association with maternal variables, except UTI, and
      the neonatal variables analyzed.

PMID- 26315472
TI  - Hysteroscopic chasing for endometrial cancer in a low-risk population: risks of
      overinvestigation.
AB  - PURPOSE: To evaluate the appropriateness of the indications for hysteroscopy
      done, in fertile and postmenopausal women, for the detection of endometrial
      cancer. METHODS: A retrospective analysis of 2673 consecutive women who underwent
      office hysteroscopy chasing for endometrial cancer between January 2012 and June
      2014. According to their medical history only low-risk women entered the study.
      RESULTS: A total of 1070 patients entered the study. The main outcome measure was
      the appropriateness of the indications for hysteroscopy. Appropriateness was
      assessed on the basis of guidelines of scientific societies and histologic
      report. According to the algorithm developed for appropriateness, 44 % of
      procedures resulted in being inappropriate. In reproductive-aged women 57 % of
      hysteroscopies were inappropriate. In postmenopausal women inappropriate
      hysteroscopies were 45 %. In reproductive-aged women, the reasons for
      inappropriateness were: absence of abnormal uterine bleeding (AUB) or AUB without
      a trial of progestin therapy. In postmenopausal women, the reasons for
      inappropriateness were: ultrasound report of endometrial thickening or polyp
      without bleeding. CONCLUSIONS: Hysteroscopy is often recommended for
      inappropriate indications. More evidence is needed to identify the risks of
      overinvestigation, overdiagnosis, and related overtreatment and to better
      identify the threshold beyond which benefits are likely to outweigh harms.

PMID- 26315473
TI  - Simultaneous detection of human papillomavirus integration and c-MYC gene
      amplification in cervical lesions: an emerging marker for the risk to
      progression.
AB  - PURPOSE: The persistence of high-risk oncogenic human papillomavirus (HR-HPV)
      infection and its integration into the host genome are key steps in the induction
      of malignant alterations. c-MYC chromosome region is a frequent localization for
      HPV insertion that has been observed in chromosome band 8q24 by fluorescence in
      situ hybridization (FISH). We report the HPV viral integration and amplification
      patterns of the c-MYC gene in cytological smears with FISH as a potential
      biomarker for the progression of squamous intraepithelial lesions (SIL). METHODS:
      HPV detection and genotyping by polymerase chain reaction (PCR) and FISH analysis
      by "Vysis Cervical FISH Probe" kit (ABBOTT Molecular Inc.) were performed in 37
      cervical samples including 8 NILM, 7 ASC-US, 7 LSIL, 3 ASC-H, 7 HSIL and 5 SCC.
      RESULTS: The results show concordance between FISH and PCR techniques for HPV
      detection. The majority of the samples contained HR-HPV, the majority being -16
      and -18 genotypes. HPV integration as determined by FISH was most frequent in
      high-risk lesions. The c-MYC gene amplification was found only in HPV-positive
      samples and was detected primarily in high-risk lesions and in cells with an
      integrated form of HPV. CONCLUSIONS: HPV integration and c-MYC gene amplification
      detected by FISH could be an important biomarker for use in clinical practice to
      determine SIL with a risk of progression.

PMID- 26315474
TI  - Thirdhand Smoke in the Homes of Medically Fragile Children: Assessing the Impact
      of Indoor Smoking Levels and Smoking Bans.
AB  - INTRODUCTION: Thirdhand smoke (THS) residue results from secondhand smoke, and is
      emerging as a distinct public health hazard, particularly for medically fragile
      pediatric patients living with smokers. THS is difficult to remove and readily
      reacts with other pollutants to form carcinogens and ultrafine particles. This
      study investigated THS found in homes of high-risk infants admitted to a neonatal
      intensive care unit and their association with characteristics (eg, number of
      household smokers) hypothesized to influence THS. METHODS: Baseline data from 141
      hospitalized infants' homes were analyzed, along with follow-up data (n = 22) to
      explore household smoking characteristics and THS changes in response to indoor
      smoking ban policies. RESULTS: Households with an indoor ban, in which not more
      than 10 cigarettes/d were smoked, had the lowest levels of THS contamination
      compared to homes with no ban (P < .001) and compared to homes with an indoor ban
      in which greater numbers of cigarettes were smoked (P < .001). Importantly, homes
      with an indoor ban in which at least 11 cigarettes/d were smoked were not
      different from homes without a ban. The follow-up sample of 22 homes provided
      initial evidence indicating that, unless a ban was implemented, THS levels in
      homes continued to increase over time. CONCLUSIONS: Preliminary longitudinal data
      suggest that THS may continue to accumulate in homes over time and household
      smoking bans may be protective. However, for homes with high occupant smoking
      levels, banning indoor smoking may not be fully adequate to protect children from
      THS. Unless smoking is reduced and bans are implemented, medically fragile
      children will be exposed to the dangers of THS.

PMID- 26315475
TI  - Flavored Tobacco Products in the United States: A Systematic Review Assessing Use
      and Attitudes.
AB  - OBJECTIVES: We systematically reviewed research examining use of and attitudes
      toward nonmenthol-flavored tobacco products to provide information relevant to a
      decision to regulate these products in the future. METHODS: To identify eligible
      studies, we searched PubMed, CINHAL, Embase, LILACS, and PsycINFO on September
      19, 2013, without date restrictions. We obtained additional studies via gray
      literature searches, expert contacts, and hand-searching citations of included
      articles. We included participants of all ages. We conducted a qualitative
      synthesis for included studies. RESULTS: The 32 studies included in this review
      exhibited substantial heterogeneity and were of varied methodological quality.
      Findings from observational, experimental, and quasiexperimental studies suggest
      that flavored tobacco use is associated with young age and that consumers may
      perceive flavored products more favorably than nonflavored products. Evidence
      from qualitative studies indicates that flavoring in tobacco is viewed favorably
      by users and nonusers of these products. CONCLUSIONS: The Food and Drug
      Administration has expressed interest in regulating flavored tobacco products.
      This systematic review strengthens the evidence base relating to this issue by
      synthesizing the literature from the United States on the use of and attitudes
      toward flavored tobacco. To address gaps in the literature, more research is
      needed to understand how flavoring impacts tobacco use over time. The evidence
      base would further be strengthened with the collection of brand-, flavor-, and
      product-specific data.

PMID- 26315476
TI  - Does using two Doppler cardiac output monitors in tandem provide a reliable trend
      line of changes for validation studies?
AB  - The demise of the pulmonary artery catheter as a gold standard in cardiac output
      measurement has created the need for new standard. Doppler cardiac output can be
      measured suprasternally (USCOM) and via the oesophagus (CardioQ). Use in tandem
      they may provide a reliable trend line of cardiac output changes against which
      new technologies can be assessed. Data from three similar clinical studies was
      pooled. Simultaneous USCOM and CardioQ readings, 13 (7-27), were performed every
      15-30 min intraoperatively. Within individual patient regression analysis was
      performed. Data was normalized, CardioQ against USCOM, to eliminate the
      systematic error component following calibration. Bland-Altman and trend,
      concordance and polar analysis, were performed on the grouped data. Cardiac
      output was indexed (CI) to BSA. Data from 53 patients, aged 59 (26-81) years,
      scheduled for major surgery were included. Within-individual mean (SD) CI was 3.4
      (0.6) L min(-1) m(-2). Correlation was good to excellent in 83 % of cases, R(2) >
      0.80, and reasonable in 96 %, R(2) > 0.60. Percentage error was 38 %, and
      decreased to 14 % with normalization. The estimated 95 % precision for a single
      Doppler reading was +/-10 %. Concordance rate was 96.6 % (confidence intervals
      94.7-99.5 %) and above the >92 % threshold for good trending ability. Polar
      analysis also confirmed good trending ability. The regression line between
      Doppler methods was offset with a slope of 0.9, thus CardioQ CI readings
      increased relative to USCOM. Both Doppler methods trended cardiac output
      reliably. Used in tandem they provide a new standard to assess cardiac output
      trending. 

PMID- 26315478
TI  - On Modelling Minimal Disease Activity.
AB  - OBJECTIVE: To explore methods for statistical modelling of minimal disease
      activity (MDA) based on data from intermittent clinic visits. METHODS: The
      analysis was based on a 2-state model. Comparisons were made between analyses
      based on "complete case" data from visits at which MDA status was known, and the
      use of hidden model methodology that incorporated information from visits at
      which only some MDA defining criteria could be established. Analyses were based
      on an observational psoriatic arthritis cohort. RESULTS: With data from 856
      patients and 7,024 clinic visits, analysis was based on virtually all visits,
      although only 62.6% provided enough information to determine MDA status.
      Estimated mean times for an episode of MDA varied from 4.18 years to 3.10 years,
      with smaller estimates derived from the hidden 2-state model analysis. Over a 10
      year period, the estimated expected times spent in MDA episodes of longer than 1
      year was 3.90 to 4.22, and the probability of having such an MDA episode was
      estimated to be 0.85 to 0.91, with longer times and greater probabilities seen
      with the hidden 2-state model analysis. CONCLUSION: A 2-state model provides a
      useful framework for the analysis of MDA. Use of data from visits at which MDA
      status can not be determined provide more precision, and notable differences are
      seen in estimated quantities related to MDA episodes based on complete case and
      hidden 2-state model analyses. The possibility of bias, as well as loss of
      precision, should be recognized when complete case analyses are used.

PMID- 26315477
TI  - Accuracy and precision of minimally-invasive cardiac output monitoring in
      children: a systematic review and meta-analysis.
AB  - Several minimally-invasive technologies are available for cardiac output (CO)
      measurement in children, but the accuracy and precision of these devices have not
      yet been evaluated in a systematic review and meta-analysis. We conducted a
      comprehensive search of the medical literature in PubMed, Cochrane Library of
      Clinical Trials, Scopus, and Web of Science from its inception to June 2014
      assessing the accuracy and precision of all minimally-invasive CO monitoring
      systems used in children when compared with CO monitoring reference methods.
      Pooled mean bias, standard deviation, and mean percentage error of included
      studies were calculated using a random-effects model. The inter-study
      heterogeneity was also assessed using an I(2) statistic. A total of 20 studies
      (624 patients) were included. The overall random-effects pooled bias, and mean
      percentage error were 0.13 +/- 0.44 l min(-1) and 29.1 %, respectively.
      Significant inter-study heterogeneity was detected (P < 0.0001, I(2) = 98.3 %).
      In the sub-analysis regarding the device, electrical cardiometry showed the
      smallest bias (-0.03 l min(-1)) and lowest percentage error (23.6 %). Significant
      residual heterogeneity remained after conducting sensitivity and subgroup
      analyses based on the various study characteristics. By meta-regression analysis,
      we found no independent effects of study characteristics on weighted mean
      difference between reference and tested methods. Although the pooled bias was
      small, the mean pooled percentage error was in the gray zone of clinical
      applicability. In the sub-group analysis, electrical cardiometry was the device
      that provided the most accurate measurement. However, a high heterogeneity
      between studies was found, likely due to a wide range of study characteristics. 

PMID- 26315479
TI  - A Promoter Polymorphism of the Vitamin D Metabolism Gene Cyp24a1 is Associated
      with Severe Atopic Dermatitis in Adults.
AB  - Atopic dermatitis (AD) is a chronic inflammatory skin disease in which genetic
      and environmental factors result in impaired epidermal barrier functioning and an
      altered immune response. Vitamin D influences these 2 pathomechanisms, and
      beneficial results have been suggested in AD. The aim of this study was to
      investigate the potential roles of the 2 essential vitamin D metabolizing
      enzymes. The frequencies of 6 common polymorphisms in the genes encoding the
      vitamin D synthesizing enzyme Cyp27b1 or the inactivating enzyme Cyp24a1 were
      assessed in 281 patients with AD and 278 healthy donors in a case-control
      setting. The Cyp24a1 rs2248359-major C allele was significantly over-represented
      in patients with AD compared with controls, which was more pronounced in patients
      with severe AD. In addition, haplotypes of the Cyp24a1 and Cyp27b1 genes were
      associated with AD. These data support that vitamin D mediates beneficial
      functions in AD and suggest that future studies on the impact of vitamin D on AD
      should consider the individual genotypes of the vitamin D metabolizing enzymes. 

PMID- 26315480
TI  - Clopidogrel inhibits angiogenesis of gastric ulcer healing via downregulation of
      vascular endothelial growth factor receptor 2.
AB  - BACKGROUND/PURPOSE: Although clopidogrel does not cause gastric mucosal injury,
      it does not prevent peptic ulcer recurrence in high-risk patients. We explored
      whether clopidogrel delays gastric ulcer healing via inhibiting angiogenesis and
      to elucidate the possible mechanisms. METHODS: Gastric ulcers were induced in
      Sprague Dawley rats, and ulcer healing and angiogenesis of ulcer margin were
      compared between clopidogrel-treated rats and controls. The expressions of the
      proangiogenic growth factors and their receptors including basic fibroblast
      growth factor (bFGF), bFGF receptor (FGFR), vascular endothelial growth factor
      (VEGF), VEGFR1, VEGFR2, platelet-derived growth factor (PDGF)A, PDGFB, PDGFR A,
      PDGFR B, and phosphorylated form of mitogenic activated protein kinase pathways
      over the ulcer margin were compared via western blot and reverse transcription
      polymerase chain reaction. In vitro, human umbilical vein endothelial cells
      (HUVECs) were used to elucidate how clopidogrel inhibited growth factors
      stimulated HUVEC proliferation. RESULTS: The ulcer sizes were significantly
      larger and the angiogenesis of ulcer margin was significantly diminished in the
      clopidogrel (2 and 10 mg/kg/d) treated groups. Ulcer induction markedly increased
      the expression of phosphorylated form of extracellular signal-regulated kinase
      (pERK), FGFR2, VEGF, VEGFR2, and PDGFRA when compared with those of normal
      mucosa. Clopidogrel treatment significantly decreased pERK, FGFR2, VEGF, VEGFR2,
      and PDGFRA expression at the ulcer margin when compared with those of the
      respective control group. In vitro, clopidogrel (10(-6)M) inhibited VEGF
      stimulated (20 ng/mL) HUVEC proliferation, at least, via downregulation of VEGFR2
      and pERK. CONCLUSION: Clopidogrel inhibits the angiogenesis of gastric ulcer
      healing at least partially by the inhibition of the VEGF-VEGFR2-ERK signal
      transduction pathway.

PMID- 26315481
TI  - Comparison of different therapies in high-risk patients with idiopathic
      membranous nephropathy.
AB  - BACKGROUND/PURPOSE: Immunosuppressive therapy plays an important role in patients
      with high-risk idiopathic membranous nephropathy (IMN), but the therapeutic
      modality is still controversial. METHODS: Corticosteroid combined with oral
      tacrolimus (TAC, target trough blood concentration of 4-8 ng/mL), intravenous
      cyclophosphamide (CYC, 750 mg/m(2)/mo, or oral mycophenolate mofetil (MMF, 1.5
      2.0 g/d) were randomly administered for 9 months to 90 patients with IMN proved
      with renal biopsy with severe proteinuria (>8 g/d). RESULTS: Eighty-six of the 90
      patients completed the study. The total remission (TR) rates in the TAC group
      were significantly higher than those in the CYC group at 1 and 2 months (p <
      0.01) and the MMF group at 1-4 months (p < 0.01). The TR rates were 83.3%, 73.3%,
      and 70.0% in the TAC, CYC, and MMF groups at 9 months (p = 0.457), and there were
      no significant differences between the three groups from 5 to 9 months.
      Furthermore, TAC reduced proteinuria and ameliorated hypoalbuminemia more quickly
      and effectively than CYC and MMF. We observed no severe adverse events in the
      three groups. CONCLUSION: Tacrolimus combined with corticosteroid had tolerable
      adverse effects and induced the remission of IMN more effectively and more
      rapidly. This is the first prospective randomized cohort study to compare three
      different therapies in patients at high risk for IMN. It provides strong evidence
      for choosing optimal treatment for patients with IMN. The long-term efficacy of
      this treatment strategy should be investigated further in future studies.

PMID- 26315482
TI  - Risk factors for in-hospital mortality in patients with type 2 diabetes
      complicated by community-acquired Klebsiella pneumoniae bacteremia.
AB  - BACKGROUND/PURPOSE: Patients with diabetes are at a high risk of infection
      related morbidity and mortality. Klebsiella pneumoniae bacilli are prevalent
      among diabetic patients, especially in Asian populations. The present study aimed
      to identify risk factors for in-hospital mortality among diabetic patients
      complicated by community-acquired K. pneumoniae bacteremia. METHODS: We evaluated
      the clinical characteristics of 341 Taiwanese type 2 diabetic patients who were
      treated for community-acquired K. pneumoniae bacteremia. We then analyzed outcome
      predictors, and in particular comorbidities and the site of infection. RESULTS:
      The overall in-hospital mortality rate was 14.1%. Comorbid cancer was the leading
      factor, accounting for 32.1% of all cases of mortality. Pulmonary infection,
      primary bacteremia, afebrile or shock presentation and low serum albumin level
      were risk factors for in-hospital mortality. Regardless of comorbidities,
      pulmonary infection [odds ratio (OR) 10.74, 95% confidence interval (CI) 2.02
      57.09] and albumin level (OR 0.15, 95% CI 0.03-0.76) were the main risk
      predictors. The receiver operating characteristic curve indicated that a serum
      albumin level lower than 2.4 g/dL (71.1% sensitivity and 77.4% specificity)
      suggested a poor prognosis in the diabetic patients with K. pneumoniae
      bacteremia. In patients with pulmonary infection, the capsular serotypes of K.
      pneumoniae were not related to poor outcomes, and an initial presentation of
      blunted fever or shock were independent factors for mortality. CONCLUSION:
      Cancer, pulmonary infection, and low serum albumin levels were independent
      indicators of in-hospital mortality in the diabetic patients complicated by K.
      pneumoniae bacteremia. The sites of infection and host characteristics should
      always elicit medical attention when treating these patients.

PMID- 26315483
TI  - YAP activates the Hippo pathway in a negative feedback loop.

PMID- 26315484
TI  - RNA Pol II as a sensor of 5caC.
AB  - Cytosines in genomic DNA come in different flavors. A recent paper published in
      Nature reveals that an oxidized variety, 5-carboxylcytosine, is recognized by the
      elongating RNA polymerase, shedding light on the role of DNA oxidation in
      transcription regulation. 

PMID- 26315485
TI  - An integrated network platform for contextual prioritization of drugs and
      pathways.
AB  - Repurposing of drugs to novel disease indications has promise for faster clinical
      translation. However, identifying the best drugs for a given pathological context
      is not trivial. We developed an integrated random walk-based network framework
      that combines functional biomolecular relationships and known drug-target
      interactions as a platform for contextual prioritization of drugs, genes and
      pathways. We show that the use of gene-centric or drug-centric data, such as gene
      expression data or a phenotypic drug screen, respectively, within this network
      platform can effectively prioritize drugs and pathways, respectively, to the
      studied biological context. We demonstrate that various genomic data can be used
      as contextual cues to effectively prioritize drugs to the studied context, while
      similarly, phenotypic drug screen data can be used to effectively prioritize
      genes and pathways to the studied phenotypic context. As a proof-of-principle, we
      showcase the use of our platform to identify known and novel drug indications
      against different subsets of breast cancers through contextual prioritization
      based on genome-wide gene expression, shRNA and drug screen and clinical survival
      data. The integrated network and associated methods are incorporated into the
      NetWalker suite for functional genomics analysis (). 

PMID- 26315486
TI  - Performance indicators evaluation of the population-based breast cancer screening
      programme in Northern Portugal using the European Guidelines.
AB  - OBJECTIVE: To evaluate the first 10 years of operation of the population-based
      breast cancer screening programme implemented in the Northern Region of Portugal,
      using selected recommended standard performance indicators. METHODS: Data from
      women aged 50-69 screened with two-view mammography, biennially, in the period
      2000-2009, were included. Main performance indicators were compared with the
      recommended levels of the European Guidelines. RESULTS: A total of 202,039
      screening examinations were performed, 71,731 (35.5%) in the initial screening
      and 130,308 (64.5%) in the subsequent screening. Coverage rate by examination
      reached 74.3% of the target population, in the last period evaluated. Recall
      rates were 8.1% and 2.4% and cancer detection rates were 4.4/1000 and 2.9/1000
      respectively, for initial and subsequent screenings. The breast cancer detection
      rate, expressed as a multiple of the background expected incidence was 3.1 in
      initial screen and 2.2 in subsequent screen. The incidence of invasive interval
      cancers met the desirable recommended levels both the first and second years
      since last screening examination, in the initial and subsequent screenings.
      Invasive tumours <15mm were 50.4% and 53.8% of the invasive cancers detected in
      initial and subsequent screenings. Less favourable size, grading and biomarkers
      expression were found in interval cancers compared to screen-detected cancers.
      CONCLUSIONS: Breast cancer screening programme in the Northern Region of Portugal
      was well accepted by the population. Most of the performance indicators were
      consistent with the desirable levels of the European Guidelines, which indicate
      an effective screening programme. Future research should verify the consistency
      of some of these results by using updated information from a larger population.

PMID- 26315488
TI  - Domestication and cereal feeding developed domestic pig-type intestinal
      microbiota in animals of suidae.
AB  - Intestinal microbiota are characterized by host-specific microorganisms, which
      have been selected through host-microbe interactions under phylogenetic evolution
      and transition of feeding behavior by the host. Although many studies have
      focused on disease-related intestinal microbiota, the origin and evolution of
      host-specific intestinal microbiota have not been well elucidated. Pig is the
      ideal mammal model to reveal the origin and evolution of host-specific intestinal
      microbiota because their direct wild ancestor and close phylogenetic neighbors
      are available for comparison. The pig has been recognized as a Lactobacillus-type
      animal. We analyzed the intestinal microbiota of various animals in Suidae:
      domestic pigs, wild boars and Red river hogs to survey the origin and evolution
      of Lactobacillus-dominated intestinal microbiota by metagenomic approach and
      following quantitative PCR confirmation. The metagenomic datasets were separated
      in two clusters; the wild animal cluster being characterized by a high abundance
      of Bifidobacterium, whereas the domesticated (or captured) animal cluster by
      Lactobacillus. In addition, Enterobacteriaceae were harbored as the major family
      only in domestic Sus scrofa. We conclude that domestication may have induced a
      larger Enterobacteriaceae population in pigs, and the introduction of modern
      feeding system further caused the development of Lactobacillus-dominated
      intestinal microbiota, with genetic and geographical factors possibly having a
      minor impact. 

PMID- 26315487
TI  - Multilayer-Coated Liquid Crystalline Nanoparticles for Effective Sorafenib
      Delivery to Hepatocellular Carcinoma.
AB  - Hepatocellular carcinoma is one of the most common cancers in adults and develops
      due to activation of oncogenes and inactivation of tumor suppressor genes.
      Sorafenib (SF) is a U.S. Food and Drug Administration (FDA) approved drug for the
      treatment of hepatocellular carcinoma. However, its clinical use is limited by
      its poor aqueous solubility and undesirable side effects. Monoolein-based liquid
      crystalline nanoparticles (LCN) are self-assembled structures that have been
      determined as promising drug-delivery vehicles. Therefore, the main aim of this
      study was to prepare layer-by-layer (LbL) polymer-assembled SF-loaded LCNs (LbL
      LCN/SF) for effective delivery of SF to hepatocellular carcinoma. Results
      revealed that LbL-LCN/SF presented optimum particle size (~165 nm) and
      polydispersity index (PDI, ~0.14) with appropriate polymer layer assembly
      confirmed by transmission electron microscopy (TEM) and atomic force microscopy
      (AFM). Furthermore, LbL-LCN/SF effectively controlled burst release and exhibited
      pH-sensitive release of SF, thereby increasing drug release in the acidic
      microenvironment of tumor cells. Compared to free SF and bare LCN, the hemolytic
      activity of LbL-LCN/SF was significantly reduced (p<0.01). Interestingly, LbL
      LCN/SF was more cytotoxic to HepG2 cells than the free drug was. Additionally,
      high cellular uptake and greater apoptotic effects of LbL-LCN/SF in HepG2 cells
      indicates superior antitumor effects. Therefore, LbL-LCN/SF is a potentially
      effective formulation for hepatocellular carcinoma.

PMID- 26315490
TI  - Left to right and right to left.

PMID- 26315489
TI  - Depression and Personality Traits Associated With Emotion Dysregulation:
      Correlates of Suicide Attempts in Women with Bulimia Nervosa.
AB  - OBJECTIVE: The objective of this study was to identify personality traits and
      psychiatric comorbidities associated with a lifetime history of a suicide attempt
      in women with bulimia nervosa (BN). METHOD: Data from two samples of women with
      BN (n = 204 and n = 133) were examined. Participants in both samples completed
      the Dimensional Assessment of Personality Pathology-Basic Questionnaire and
      reported whether they had ever had a lifetime suicide attempt. Comorbid
      psychopathology was based on self-reported questionnaire and interview data.
      Univariate and multivariate logistic regression analyses were run, predicting a
      lifetime suicide attempt. RESULTS: Based on the Dimensional Assessment of
      Personality Pathology-Basic Questionnaire, identity problems were associated with
      a lifetime suicide attempt in both samples; cognitive dysregulation, anxiousness
      and insecure attachment were associated with a lifetime suicide attempt in one
      but not both samples. Lifetime anxiety disorder was associated with a lifetime
      suicide attempt in one sample, and depression was associated with a lifetime
      suicide attempt in both samples. Multivariate analyses revealed that only
      depression was uniquely associated with a lifetime suicide attempt in both
      samples. DISCUSSION: Although personality traits associated with aspects of
      emotion dysregulation were associated with a lifetime suicide attempt, depression
      was found to have the strongest association with a lifetime suicide attempt in
      two samples of women with BN. These findings suggest that depression severity may
      be the most important target of treatment and suicide prevention efforts in women
      with BN.

PMID- 26315491
TI  - Permanent pacemaker implantation after aortic valve replacement: Long-term
      dependency or rhythm recovery?
AB  - INTRODUCTION: Conduction disturbances requiring permanent pacemaker (PM)
      implantation occur in 3-12% of patients after aortic valve replacement (AVR). Our
      aim was to assess long-term PM dependency and its predictors in these patients.
      METHODS: We conducted a retrospective study of all consecutive patients
      undergoing permanent PM implantation after AVR between January 2004 and December
      2010. Absence of sinus rhythm or atrial fibrillation with appropriate ventricular
      response at a pacing rate of 30 bpm for 10 s was defined as pacemaker dependency.
      RESULTS: Ninety-one patients underwent permanent PM implantation and during
      follow-up (1026.6 +/- 732.0 days) 64% of them did not recover rhythm. Age,
      conduction disorders on the preoperative ECG, negative chronotropic medication
      before surgery, cardiopulmonary bypass and aortic cross-clamp times did not
      influence rhythm recovery. In multivariate analysis, valvular disease etiology
      related to endocarditis, prosthetic dysfunction and bicuspid valve were
      associated with long-term PM dependency (OR 5.05; CI: 1.43-17.75). CONCLUSIONS:
      The majority of patients undergoing permanent PM implantation after AVR did not
      recover from conduction disorders during follow-up. The etiology of valvular
      disease was an independent predictor of late PM dependence.

PMID- 26315492
TI  - An endostatin-derived peptide orally exerts anti-fibrotic activity in a murine
      pulmonary fibrosis model.
AB  - OBJECTIVE: Pulmonary fibrosis causes high morbidity and mortality in affected
      individuals. Recently, we showed that parenteral or intratracheal administration
      of a peptide derived from endostatin, called E4, prevents and ameliorates
      fibrosis using different models of dermal and pulmonary disease. No marketed
      orally delivered peptide drugs are currently available for progressive pulmonary
      fibrosis; however oral delivery of drugs is the preferred route for treating most
      chronic diseases. Thus, we investigated whether oral administration of E4 peptide
      exerted anti-fibrotic activity in a murine pulmonary fibrosis model. METHODS:
      Bleomycin (1.2mU/g body weight) was intratracheally administrated to male 6-8
      week-old C57BL/6J mice. E4 peptide (20, 10, 5, and 1 MUg/mouse) or scrambled
      control peptide (20 MUg/mouse) was orally administered on the same day as
      bleomycin. In some experiments, E4 peptide (10 and 5 MUg/mouse) was orally
      administered three times on days 0, 3, and 6 post-bleomycin treatment. Lungs were
      harvested on day 21 for histological analysis and hydroxyproline assay. RESULTS:
      Histological analysis and hydroxyproline assay revealed that bleomycin
      successfully induced pulmonary fibrosis, and that 20 MUg of oral E4 peptide
      ameliorated the fibrosis. The lower doses of E4 peptide (10, 5, and 1 MUg) were
      insufficient to exert anti-fibrotic activity when given as a single dose.
      Multiple doses of E4 peptide efficiently exerted anti-fibrotic activity even at
      lower doses. CONCLUSION: E4 peptide shows oral bioavailability and exerts anti
      fibrotic activity in a bleomycin-induced pulmonary fibrosis model. We suggest
      that E4 peptide is a novel oral drug for fibroproliferative disorders.

PMID- 26315493
TI  - Inhibitory effect of antidepressant drugs on contact hypersensitivity reaction is
      connected with their suppressive effect on NKT and CD8(+) T cells but not on TCR
      delta T cells.
AB  - BACKGROUND: Contact hypersensitivity (CHS) reaction induced by a topical
      application of hapten is a cell-mediated antigen-specific type of skin
      inflammation mediated by interaction of several subtypes of T cell
      subpopulations. Recently, it has been shown that antidepressant drugs inhibit CHS
      reaction, although the mechanism of this effect remains unknown. The aim of the
      present study was to investigate the effect of 2-week desipramine or fluoxetine
      administration on the CHS reaction induced by picryl chloride (PCL) application
      in B10.PL mice and in knock-out mice established on B10.PL background: TCRdelta(
      /-) mice lacking TCRgammadelta T lymphocytes; beta2m(-/-) mice lacking CD8(+) T
      lymphocytes and CD1d(-/-) mice lacking CD1d dependent natural killer T (NKT)
      lymphocytes. METHODS: B10.PL, TCRdelta(-/-), beta2m(-/-) and CD1d(-/-) mice were
      divided into six groups: 1) vehicle-treated negative control group; 2)
      desipramine-treated negative control group; 3) fluoxetine-treated negative
      control group; 4) vehicle and PCL-treated group (positive control group); 5)
      desipramine and PCL-treated group; and 6) fluoxetine and PCL-treated group. CHS
      to PCL was tested by evaluation of ear swelling. Metabolic activity of spleen and
      lymph node cells were estimated by MTT test. RESULTS: The antidepressants
      significantly suppressed the CHS reaction in B10.PL mice: desipramine by 55% and
      fluoxetine by 42% compared to the positive control. This effect was even stronger
      in TCRdelta(-/-) mice, in which fluoxetine reduced the ear swelling by 73% in
      comparison with the vehicle-treated positive control group. On the other hand,
      desipramine and fluoxetine did not inhibit CHS reaction in beta2m(-/-) and CD1d(
      /-) mice. Moreover, PCL increased metabolic and/or proliferative activity of
      splenocytes in all four strains of mice whereas the antidepressants decreased
      this activity of splenocytes in B10.PL, TCRdelta(-/-) and CD1d(-/-) mice.
      CONCLUSION: The results of the present study show that lack of CD8(+) T cells or
      NKT cells abolishes the immunosuppressive effect of antidepressant drugs on PCL
      induced CHS reaction in mice. These results suggest that antidepressant drug
      induced inhibition of CHS reaction is connected with their inhibitory effect on
      ability of CD8(+) T cells and NKT cells to induce and/or escalate CHS reaction.
      TCRgammadelta cells seem not to be involved in antidepressant-induced suppression
      of CHS.

PMID- 26315494
TI  - Building up the machinery for DNA replication.

PMID- 26315495
TI  - Analysis of small carbohydrates in several bioactive botanicals by gas
      chromatography with mass spectrometry and liquid chromatography with tandem mass
      spectrometry.
AB  - Bioactive botanicals contain natural compounds with specific biological activity,
      such as antibacterial, antioxidant, immune stimulating, and taste improving. A
      full characterization of the chemical composition of these botanicals is
      frequently necessary. A study of small carbohydrates from the plant materials of
      18 bioactive botanicals is further described. The study presents the
      identification of the carbohydrate using a gas chromatographic-mass spectrometric
      analysis that allows detection of molecules as large as maltotetraose, after
      changing them into trimethylsilyl derivatives. A number of carbohydrates in the
      plant (fructose, glucose, mannose, sucrose, maltose, xylose, sorbitol, and myo-,
      chiro-, and scyllo-inositols) were quantitated using a novel liquid
      chromatography with tandem mass spectrometric technique. Both techniques involved
      new method developments. The gas chromatography with mass spectrometric analysis
      involved derivatization and separation on a Rxi((r))-5Sil MS column with H2 as a
      carrier gas. The liquid chromatographic separation was obtained using a
      hydrophilic interaction type column, YMC-PAC Polyamine II. The tandem mass
      spectrometer used an electrospray ionization source in multiple reaction
      monitoring positive ion mode with the detection of the adducts of the
      carbohydrates with Cs(+) ions. The validated quantitative procedure showed
      excellent precision and accuracy allowing the analysis in a wide range of
      concentrations of the analytes.

PMID- 26315496
TI  - Synthesis of Triphenylene-Based Triptycenes via Suzuki-Miyaura Cross-Coupling and
      Subsequent Scholl Reaction.
AB  - A two-step method (Suzuki-Miyaura cross-coupling, followed by Scholl oxidation)
      to triphenylene-based triptycenes is described, rendering a variety of pi
      extended triptycenes accessible in high yields and without the necessity of
      column chromatography purification. The versatility of this reaction has been
      demonstrated in the synthesis of a supertriptycene in only four steps and high
      yields. 

PMID- 26315497
TI  - Evaluation of the Effect of 1,3-Bis(4-Phenyl)-1H-1,2,3-Triazolyl-2-Propanolol on
      Gene Expression Levels of JAK2-STAT3, NF-kappaB, and SOCS3 in Cells Cultured from
      Biopsies of Mammary Lesions.
AB  - Breast cancer is the most frequent neoplasia in women and is responsible for
      approximately 13.8% of deaths per year for this gender. It has been suggested
      that JAK2, STAT3, and NF-kappaB gene expression is involved in this type of
      cancer. The objective of the present study was to determine the effect of
      bistriazole in these signaling pathways in patients with breast cancer and benign
      mammary lesions. The inhibitory concentration 50 of bistriazole was calculated in
      cell cultures of patients with benign lesions, Probit = 4.6 MUM with IC = 95%.
      The study was performed by examining 63 women who submitted to mammary biopsies.
      Biopsies of the mammary lesions were performed, gene expression was determined,
      and cells were cultured in the presence of 4.6 MUM bistriazole. We found that
      breast cancer is related to age greater than 50 (P <= 0.01), being overweight (P
      <= 0.023) and having a waist circumference larger than 80 cm (P <= 0.01). The
      gene expression of JAK2, STAT3, and NF-kappaB was higher in groups of patients
      with breast cancer, while SOCS3 expression was lower. After being exposed to
      bistriazole, the expression of JAK2 and STAT3 decreased, and the expression of
      SOCS3 and NF-kappaB increased. In conclusion, this molecule in development has an
      effect on the gene expression of JAK3 and STAT3; nevertheless, the lack of change
      in NF-kappaB indicates that it is not a regulator of inflammation, and therefore,
      more studies should be performed. 

PMID- 26315498
TI  - Erratum to: Abnormal Myocardial Strain Indices in Children Receiving
      Anthracycline Chemotherapy.
AB  - Erratum to: Pediatr Cardiol DOI 10.1007/s00246-015-1203-8. The original version
      of this article unfortunately contained a mistake in the author's group. The
      given name of Payam Ghazi was misspelled and the first and middle names of John
      Lynn Jefferies were interchanged. The two co-author names are corrected with this
      erratum.

PMID- 26315499
TI  - In vivo reprogrammed pluripotent stem cells from teratomas share analogous
      properties with their in vitro counterparts.
AB  - Recently, induced pluripotent stem cells (iPSCs) have been generated in vivo from
      reprogrammable mice. These in vivo iPSCs display features of totipotency, i.e.,
      they differentiate into the trophoblast lineage, as well as all 3 germ layers.
      Here, we developed a new reprogrammable mouse model carrying an Oct4-GFP reporter
      gene to facilitate the detection of reprogrammed pluripotent stem cells. Without
      doxycycline administration, some of the reprogrammable mice developed
      aggressively growing teratomas that contained Oct4-GFP(+) cells. These teratoma
      derived in vivo PSCs were morphologically indistinguishable from ESCs, expressed
      pluripotency markers, and could differentiate into tissues of all 3 germ layers.
      However, these in vivo reprogrammed PSCs were more similar to in vitro iPSCs than
      ESCs and did not contribute to the trophectoderm of the blastocysts after
      aggregation with 8-cell embryos. Therefore, the ability to differentiate into the
      trophoblast lineage might not be a unique characteristic of in vivo iPSCs. 

PMID- 26315500
TI  - Trajectories of Anxiety Among Women with Breast Cancer: A Proxy for Adjustment
      from Acute to Transitional Survivorship.
AB  - Anxiety is one of the main components of distress among women with breast cancer
      (BC), particularly in the early stages of the disease. Changes in anxiety over
      time may reflect the process of adjustment or lack thereof. The process of
      adjustment in the traverse of acute to transitional stages of survivorship
      warrants further examination. To examine the trajectory of anxiety and the
      specific patterns that may indicate a lack of adjustment within 2 years following
      BC surgery, survey data from a 2-year prospective cohort study of 725 women with
      BC were analyzed by Mixture Growth Modelling and logistic regression and Analysis
      of Variance. A piece-wise growth curve displayed the best fit to the data,
      indicating a significant decrease in anxiety in the first year, followed by a
      slower rate of change during the second year. Four classes of trajectories were
      identified: High Stable, High Decrease, Mild Decrease, and Low Decrease. Of
      these, High Stable anxiety showed the most substantive indications of lack of
      adjustment. This subgroup was predominantly characterized by sociodemographic
      variables such as financial difficulties. Our results support an emphasis on the
      transitional nature of the stage that follows the end of primary active treatment
      and imply a need for supportive follow up care for those who display lack of
      adjustment at this stage.

PMID- 26315502
TI  - JHSB Policy Brief. Does Medical Treatment of Children's Behavioral Problems Lower
      Foster Care Rates?

PMID- 26315501
TI  - Educational Inequalities in Health Behaviors at Midlife: Is There a Role for
      Early-life Cognition?
AB  - Education is a fundamental cause of social inequalities in health because it
      influences the distribution of resources, including money, knowledge, power,
      prestige, and beneficial social connections, that can be used in situ to
      influence health. Recent studies have highlighted early-life cognition as
      commonly indicating the propensity for educational attainment and determining
      health and age of mortality. Health behaviors provide a plausible mechanism
      linking both education and cognition to later-life health and mortality. We
      examine the role of education and cognition in predicting smoking, heavy
      drinking, and physical inactivity at midlife using data from the Wisconsin
      Longitudinal Study (N = 10,317), National Survey of Health and Development (N =
      5,362), and National Childhood Development Study (N = 16,782). Adolescent
      cognition was associated with education but was inconsistently associated with
      health behaviors. Education, however, was robustly associated with improved
      health behaviors after adjusting for cognition. Analyses highlight structural
      inequalities over individual capabilities when studying health behaviors. 

PMID- 26315503
TI  - Editor's Note: Karraker and Latham Republication.

PMID- 26315504
TI  - In Sickness and in Health? Physical Illness as a Risk Factor for Marital
      Dissolution in Later Life.
AB  - The health consequences of marital dissolution are well known, but little work
      has examined the impact of health on the risk of marital dissolution. We use a
      sample of 2,701 marriages from the Health and Retirement Study to examine the
      role of serious physical illness onset in subsequent marital dissolution via
      either divorce or widowhood. We use a series of discrete time event history
      models with competing risks to estimate the impact of husband's and wife's
      physical illness onset on risk of divorce and widowhood. We find that only
      measures of wife's illness onset are associated with elevated risk of divorce,
      while measures of either spouse's illness onset is associated with elevated risk
      of widowhood. Further, in the case of heart problems, we find that this gender
      difference is statistically significant. These findings suggest health as a
      determinant of marital dissolution in later life via both biological and gendered
      social pathways. 

PMID- 26315505
TI  - Paracrine effect of inflammatory cytokine-activated bone marrow mesenchymal stem
      cells and its role in osteoblast function.
AB  - Mesenchymal stem cells (MSCs) have a crucial function in bone regeneration.
      Inflammation is a well-documented component of the osteogenic microenvironment.
      In the present study, we investigated whether stimulation of MSCs with
      inflammatory cytokines promotes osteogenesis through a paracrine mediator. MSCs
      were pre-stimulated with the inflammatory factors IFN-gamma and TNF-alpha. After
      pre-stimulation, the MSC secretion levels of IL-6, HGF, VEGF, and TGF-beta were
      significantly elevated (p < 0.01); however, the production of IL-2, IL-4, and IL
      10 was not changed (p > 0.05). MG63, an osteoblast-like cell line, was cultured
      in different MSC-conditioned media. After treatment with conditioned media
      collected from MSCs pre-treated with cytokines, the proliferation and migration
      of MG63 cells were significantly improved, and the expression levels of the
      osteoblast differentiation markers ALP, COLI, OCN and OPN were significantly
      increased as revealed by a quantitative PCR analysis (p < 0.05). Furthermore, an
      immunofluorescence staining assay showed that more MG63 cells were OPN-positive,
      while an Alizarin red staining indicated the increased formation of calcium
      nodules in the IFN-gamma and TNF-alpha combined pretreatment group. The results
      indicated that conditioned medium from inflammatory cytokine-activated MSCs can
      significantly promote osteoblast proliferation, migration, differentiation, and
      mineralization and ultimately enhance osteogenesis through paracrine mechanisms.
      These findings present a new direction for the clinical application of MSCs in
      the repair of bone defects. 

PMID- 26315506
TI  - A quantitative method for evaluating numerical simulation accuracy of time
      transient Lamb wave propagation with its applications to selecting appropriate
      element size and time step.
AB  - Lamb wave technique has been widely used in non-destructive evaluation (NDE) and
      structural health monitoring (SHM). However, due to the multi-mode
      characteristics and dispersive nature, Lamb wave propagation behavior is much
      more complex than that of bulk waves. Numerous numerical simulations on Lamb wave
      propagation have been conducted to study its physical principles. However, few
      quantitative studies on evaluating the accuracy of these numerical simulations
      were reported. In this paper, a method based on cross correlation analysis for
      quantitatively evaluating the simulation accuracy of time-transient Lamb waves
      propagation is proposed. Two kinds of error, affecting the position and shape
      accuracies are firstly identified. Consequently, two quantitative indices, i.e.,
      the GVE (group velocity error) and MACCC (maximum absolute value of cross
      correlation coefficient) derived from cross correlation analysis between a
      simulated signal and a reference waveform, are proposed to assess the position
      and shape errors of the simulated signal. In this way, the simulation accuracy on
      the position and shape is quantitatively evaluated. In order to apply this
      proposed method to select appropriate element size and time step, a specialized
      2D-FEM program combined with the proposed method is developed. Then, the proper
      element size considering different element types and time step considering
      different time integration schemes are selected. These results proved that the
      proposed method is feasible and effective, and can be used as an efficient tool
      for quantitatively evaluating and verifying the simulation accuracy of time
      transient Lamb wave propagation. 

PMID- 26315507
TI  - Partial mGlu5 Negative Allosteric Modulators Attenuate Cocaine-Mediated Behaviors
      and Lack Psychotomimetic-Like Effects.
AB  - Cocaine abuse remains a public health concern for which pharmacotherapies are
      largely ineffective. Comorbidities between cocaine abuse, depression, and anxiety
      support the development of novel treatments targeting multiple symptom clusters.
      Selective negative allosteric modulators (NAMs) targeting the metabotropic
      glutamate receptor 5 (mGlu5) subtype are currently in clinical trials for the
      treatment of multiple neuropsychiatric disorders and have shown promise in
      preclinical models of substance abuse. However, complete blockade or inverse
      agonist activity by some full mGlu5 NAM chemotypes demonstrated adverse effects,
      including psychosis in humans and psychotomimetic-like effects in animals,
      suggesting a narrow therapeutic window. Development of partial mGlu5 NAMs,
      characterized by their submaximal but saturable levels of blockade, may represent
      a novel approach to broaden the therapeutic window. To understand potential
      therapeutic vs adverse effects in preclinical behavioral assays, we examined the
      partial mGlu5 NAMs, M-5MPEP and Br-5MPEPy, in comparison with the full mGlu5 NAM
      MTEP across models of addiction and psychotomimetic-like activity. M-5MPEP, Br
      5MPEPy, and MTEP dose-dependently decreased cocaine self-administration and
      attenuated the discriminative stimulus effects of cocaine. M-5MPEP and Br-5MPEPy
      also demonstrated antidepressant- and anxiolytic-like activity. Dose-dependent
      effects of partial and full mGlu5 NAMs in these assays corresponded with
      increasing in vivo mGlu5 occupancy, demonstrating an orderly occupancy-to
      efficacy relationship. PCP-induced hyperlocomotion was potentiated by MTEP, but
      not by M-5MPEP and Br-5MPEPy. Further, MTEP, but not M-5MPEP, potentiated the
      discriminative-stimulus effects of PCP. The present data suggest that partial
      mGlu5 NAM activity is sufficient to produce therapeutic effects similar to full
      mGlu5 NAMs, but with a broader therapeutic index. 

PMID- 26315509
TI  - A strange finding in the common bile duct.

PMID- 26315508
TI  - Prevention of Trauma and Stressor-Related Disorders: A Review.
AB  - Posttraumatic stress disorder (PTSD) is a common, frequently chronic, and
      disabling condition which, along with acute stress disorder (ASD), is categorized
      as a trauma- and stressor-related disorder by the DSM-5. These disorders are
      unique in requiring exposure to a severe stressor, which implies that potential
      sufferers could be identified and helped before developing a disorder. Research
      on prevention strategies for stress-related disorders has taken a number of
      avenues, including intervention before and after trauma and the use of both
      psychosocial and somatic approaches. Despite advances in neurobiological
      understanding of response to trauma, clinical evidence for preventive
      interventions remains sparse. This review provides an overview of prevention
      approaches and summarizes the existing literature on prevention of ASD and PTSD,
      including clinical and preclinical studies. Given the potential benefits to
      trauma survivors and society, the development of effective preventive
      interventions should be given greater priority. Resources should be directed to
      adequately test promising interventions in clinical trials, and research should
      be conducted according to translational research principles in which preclinical
      research informs the design of clinical studies. 

PMID- 26315511
TI  - A review of the evidence on reducing macrovascular risk in patients with
      atherogenic dyslipidaemia: A report from an expert consensus meeting on the role
      of fenofibrate-statin combination therapy.
AB  - A meeting of European experts in cardiovascular (CV) disease and lipids was
      convened in Paris, France, on 10 November 2014 to discuss lipid profile, and in
      particular atherogenic dyslipidaemia (AD), and associated CV risk. Key points
      that were raised and discussed during the meeting are summarised in this paper,
      which also accounts for further discussion and agreement on these points by the
      group of experts. Elevated levels of low-density lipoprotein cholesterol (LDL-c)
      are commonly associated with a greater CV risk than low LDL-c levels, and are
      routinely managed with statins. However, even for patients controlled on statins
      and achieving low LDL-c levels, abnormal lipid profiles observed in some patients
      (i.e. elevated triglyceride levels, with/without low levels of high-density
      lipoprotein cholesterol [HDL-c]) have been linked to the presence of a residual
      CV risk. Therefore, it is recommended that both triglyceride and HDL-c levels be
      measured, to allow for the overall CV residual risk to be adequately managed.
      Favourable safety and clinical data support the combination of statins with other
      lipid-lowering agents, such as fenofibrate. Patients who have elevated
      triglyceride levels plus low levels of HDL-c are most likely to achieve clinical
      benefit from fenofibrate-statin combination therapy. In these patients with AD,
      achieving target non-HDL-c levels should be a key focus of CV risk management,
      and the use of non-HDL-c was advocated to provide a better measure of CV risk
      than LDL-c levels. 

PMID- 26315510
TI  - Associations between circulating endostatin levels and vascular organ damage in
      systemic sclerosis and mixed connective tissue disease: an observational study.
AB  - INTRODUCTION: Systemic sclerosis (SSc) and mixed connective tissue disease (MCTD)
      are chronic immune-mediated disorders complicated by vascular organ damage. The
      aim of this study was to examine the serum levels of the markers of
      neoangiogenesis: endostatin and vascular endothelial growth factor (VEGF), in our
      unselected cohorts of SSc and MCTD. METHODS: Sera of SSc patients (N = 298) and
      MCTD patients (N = 162) from two longitudinal Norwegian cohorts were included.
      Blood donors were included as controls (N = 100). Circulating VEGF and endostatin
      were analyzed by enzyme immunoassay. RESULTS: Mean endostatin levels were
      increased in SSc patients 93.7 (37) ng/ml (P < .001) and MCTD patients 83.2 (25)
      ng/ml (P < .001) compared to controls 65.1 (12) ng/ml. Median VEGF levels were
      elevated in SSc patients 209.0 (202) pg/ml compared to MCTD patients 181.3 (175)
      pg/ml (P = .017) and controls 150.0 (145) pg/ml (P < .001). Multivariable
      analysis of SSc subsets showed that pulmonary arterial hypertension (coefficient
      15.7, 95 % CI: 2.2-29.2, P = .023) and scleroderma renal crisis (coefficient
      77.6, 95 % CI: 59.3-100.0, P < .001) were associated with elevated endostatin
      levels. Multivariable analyses of MCTD subsets showed that digital ulcers were
      associated with elevated endostatin levels (coefficient 10.5, 95 % CI: 3.2-17.8,
      P = .005). The risk of death increased by 1.6 per SD endostatin increase (95 %
      CI: 1.2-2.1, P = .001) in the SSc cohort and by 1.6 per SD endostatin increase
      (95 % CI: 1.0-2.4, P = .041) in the MCTD cohort after adjustments to known risk
      factors. CONCLUSIONS: Endostatin levels were elevated in patients with SSc and
      MCTD, particularly SSc patients with pulmonary arterial hypertension and
      scleroderma renal crisis, and MCTD patients with digital ulcers. Elevated
      endostatin levels were also associated with increased all-cause mortality during
      follow-up in both groups of patients. We propose that endostatin might indicate
      the degree of vascular injury in SSc and MCTD patients.

PMID- 26315513
TI  - Dealing with bullying and harassment: a practical guide for Australasian
      emergency medicine trainees.

PMID- 26315512
TI  - The wheat resistance gene Lr34 results in the constitutive induction of multiple
      defense pathways in transgenic barley.
AB  - The wheat gene Lr34 encodes an ABCG-type transporter which provides durable
      resistance against multiple pathogens. Lr34 is functional as a transgene in
      barley, but its mode of action has remained largely unknown both in wheat and
      barley. Here we studied gene expression in uninfected barley lines transgenic for
      Lr34. Genes from multiple defense pathways contributing to basal and inducible
      disease resistance were constitutively active in seedlings and mature leaves. In
      addition, the hormones jasmonic acid and salicylic acid were induced to high
      levels, and increased levels of lignin as well as hordatines were observed. These
      results demonstrate a strong, constitutive re-programming of metabolism by Lr34.
      The resistant Lr34 allele (Lr34res) encodes a protein that differs by two amino
      acid polymorphisms from the susceptible Lr34sus allele. The deletion of a single
      phenylalanine residue in Lr34sus was sufficient to induce the characteristic Lr34
      based responses. Combination of Lr34res and Lr34sus in the same plant resulted in
      a reduction of Lr34res expression by 8- to 20-fold when the low-expressing
      Lr34res line BG8 was used as a parent. Crosses with the high-expressing Lr34res
      line BG9 resulted in an increase of Lr34sus expression by 13- to 16-fold in
      progenies that inherited both alleles. These results indicate an interaction of
      the two Lr34 alleles on the transcriptional level. Reduction of Lr34res
      expression in BG8 crosses reduced the negative pleiotropic effects of Lr34res on
      barley growth and vigor without compromising disease resistance, suggesting that
      transgenic combination of Lr34res and Lr34sus can result in agronomically useful
      resistance. 

PMID- 26315514
TI  - Cancer Genetics and Implications for Clinical Management.
AB  - There is now compelling evidence that the molecular heterogeneity of cancer is
      associated with disparate phenotypes with variable outcomes and therapeutic
      responsiveness to therapy in histologically indistinguishable cancers. This
      diversity may explain why conventional clinical trial designs have mostly failed
      to show efficacy when patients are enrolled in an unselected fashion. Knowledge
      of the molecular phenotype has the potential to improve therapeutic selection and
      hence the early delivery of the optimal therapeutic regimen. Resolution of the
      challenges associated with a more stratified approach to health care will ensure
      more precise diagnostics and enhance therapeutic selection, which will improve
      overall outcomes. 

PMID- 26315516
TI  - Principles of Cancer Screening.
AB  - Cancer screening has long been an important component of the struggle to reduce
      the burden of morbidity and mortality from cancer. Notwithstanding this history,
      many aspects of cancer screening remain poorly understood. This article presents
      a summary of basic principles of cancer screening that are relevant for
      researchers, clinicians, and public health officials alike. 

PMID- 26315517
TI  - Lung Cancer Screening.
AB  - Screening for lung cancer in high-risk individuals with annual low-dose computed
      tomography has been shown to reduce lung cancer mortality by 20% and is
      recommended by multiple health care organizations. Lung cancer screening is not a
      specific test; it is a process that involves appropriate selection of high-risk
      individuals, careful interpretation and follow-up of imaging, and annual testing.
      Screening should be performed in the context of a multidisciplinary program
      experienced in the diagnosis and management of lung nodules and early-stage lung
      cancer. 

PMID- 26315515
TI  - The Triple-Code Model for Pancreatic Cancer: Cross Talk Among Genetics,
      Epigenetics, and Nuclear Structure.
AB  - Pancreatic adenocarcinoma is painful, generally incurable, and frequently lethal.
      The current progression model indicates that this cancer evolves by mutations and
      deletions in key oncogenes and tumor suppressor genes. This article describes an
      updated, more comprehensive model that includes concepts from the fields of
      epigenetics and nuclear architecture. Widespread use of next-generation
      sequencing for identifying genetic and epigenetic changes genome-wide will help
      identify and validate more and better markers for this disease. Epigenetic
      alterations are amenable to pharmacologic manipulations, thus this new integrated
      paradigm will contribute to advance this field from a mechanistic and
      translational point of view. 

PMID- 26315518
TI  - Colorectal Cancer Screening.
AB  - Colorectal cancer (CRC) is a leading cause of cancer morbidity and mortality in
      the Western world. Advances in surgical and medical management have led to
      improved outcomes; however, the prognosis of CRC is often poor when detected at a
      symptomatic stage. Most cases of CRC develop over years from removable well
      defined precursor lesions, and asymptomatic, curable disease may be detected by
      convenient noninvasive tests. These features make CRC a suitable candidate for
      screening, and several options are available. This article outlines the evidence
      for established CRC screening tests along with a discussion on newer tests and
      ongoing research. 

PMID- 26315519
TI  - Breast Cancer Screening.
AB  - Breast cancer screening has become a controversial topic. Understanding the
      points of contention requires an appreciation of the conceptual framework
      underpinning cancer screening in general, knowledge of the strengths and
      limitations of available screening modalities, and familiarity with published
      clinical trial data. This review is data intense with the intention of presenting
      enough information to permit the reader to enter into the discussion with an
      ample knowledge base. The focus throughout is striking a balance between the
      benefits and harms of breast cancer screening. 

PMID- 26315520
TI  - Screening for Viral Hepatitis and Hepatocellular Cancer.
AB  - Accurate tests for at-risk populations are available for hepatitis B virus,
      hepatitis C virus (HCV), and hepatocellular carcinoma (HCC). Effective treatments
      for all three diseases exist if diagnosed early. New antivirals are making a
      significant impact on HCV. Liver transplant is curative for early HCC and is
      prioritized by the United Network for Organ Sharing in the United States.
      Screening and surveillance for deadly disease only makes sense if there are
      identifiable populations at risk for the condition, there are sensitive and
      specific low-cost tests available for the condition, and there are effective
      treatments for the condition. 

PMID- 26315521
TI  - Prostate Cancer Screening and the Associated Controversy.
AB  - Prostate cancer is the most common malignancy diagnosed in men and the second
      leading cause of cancer death for men in the United States. Widespread use of
      prostate-specific antigen (PSA) screening led to a decrease in mortality;
      however, PSA screening may have led to overdiagnosis and overtreatment of
      clinically insignificant cancers. The US Preventive Services Task Force (USPSTF)
      released a statement recommending against the use of PSA, which was met with
      concern from professional organizations. This article reviews the epidemiology of
      prostate cancer, data from the largest screening trials, USPSTF recommendation
      statement, and current strategies used to improve overdiagnosis and
      overtreatment. 

PMID- 26315522
TI  - Screening for Pancreatic Cancer.
AB  - Neither extended surgery nor extended indication for surgery has improved
      survival in patients with pancreatic cancer. According to autopsy studies,
      presumably 90% are metastatic. The only cure is complete removal of the tumor at
      an early stage before it becomes a systemic disease or becomes invasive. Early
      detection and screening of individuals at risk is currently under way. This
      article reviews the evidence and methods for screening, either familial or
      sporadic. Indication for early-stage surgery and precursors are discussed.
      Surgeons should be familiar with screening because it may provide patients with a
      chance for cure by surgical resection. 

PMID- 26315523
TI  - Screening and Early Detection of Gastric Cancer: East Versus West.
AB  - Low ratio of mortality over incidence of gastric cancer in Asian countries
      including Korea and Japan could be explained by early detection after screening,
      different treatment strategy, or genetic disparity between the East and West.
      Early detection after screening program for gastric cancer and subsequent
      surgical treatment including appropriate lymph node dissection has been developed
      successfully in high risk areas such as East Asian countries. Even in countries
      with a low prevalence of gastric cancer, a specific screening program is
      recommended for any high-risk population. 

PMID- 26315525
TI  - Personalized Approaches to Gastrointestinal Cancers: Importance of Integrating
      Genomic Information to Guide Therapy.
AB  - Cancers are characterized by complex tumor heterogeneity driven by subclones with
      differential genotypes and phenotypes, which then drives cancer behavior. As
      genomic strategies become feasible on smaller samples such as biopsies, coupled
      with decreasing costs of these approaches, clinicians will increasingly use
      genomic information to drive therapeutic decision making. Early applications of
      such personalized approaches are discussed. Genetic testing of high-risk family
      members may identify patients with germline mutations who can have prophylactic
      surgeries as a cancer prevention strategy. This article discusses examples of
      successful targeted therapy. Clinical trials need to incorporate genetic testing
      to stratify patients into different groups. 

PMID- 26315524
TI  - Hereditary Colorectal Cancer: Genetics and Screening.
AB  - Colorectal cancer (CRC) is the third most common cancer and the third leading
      cause of cancer death in men and women in the United States. About 30% of
      patients with CRC report a family history of CRC. However, only 5% of CRCs arise
      in the setting of a well-established mendelian inherited disorder. In addition,
      serrated polyposis is a clinically defined syndrome with multiple serrated polyps
      in the colorectum and an increased CRC risk for which the genetics are unknown.
      This article focuses on genetic and clinical aspects of Lynch syndrome, familial
      adenomatous polyposis, and MUTYH-associated polyposis. 

PMID- 26315526
TI  - Cancer Screening and Genomics.

PMID- 26315527
TI  - Cancer Screening and Genetics. Preface.

PMID- 26315528
TI  - Glycosphingolipids and oxidative stress: evaluation of hydroxyl radical oxidation
      of galactosyl and lactosylceramides using mass spectrometry.
AB  - Galactosylceramide (GalCer) and lactosylceramide (LacCer) are structural and
      signaling lipids, playing important roles in signal transduction and cell
      adhesion. They are especially abundant in the nervous system and in important
      components of the myelin sheath. Although neurodegenerative disorders are
      associated with increased oxidative stress and lipid oxidation, the connection
      between oxidative stress and glycosphingolipid modification has been scarcely
      addressed. In this study, we aimed to characterize the structural changes caused
      by the hydroxyl radical to GalCer and LacCer molecular species using electrospray
      ionization mass spectrometry (ESI-MS and MS/MS) and high performance liquid
      chromatography-tandem mass spectrometry (HPLC-MS(n)). ESI-MS and LC-MS spectra of
      24:1GalCer and 24:1LacCer after free radical oxidation showed the formation of
      new species, which were identified as keto, hydroxyl and hydroperoxy derivatives,
      arising from modification in the mono unsaturated fatty acyl chain. Formation of
      ceramide and oxidized ceramides was also observed as a result of 24:1GalCer and
      24:1LacCer radical oxidation. 24:1GlcCer (glucosylceramide) was detected after
      LacCer oxidation, probably due to oxidative cleavage of lactosyl moiety. This
      study shows that glycosphingolipids are prone to radical induced oxidation, which
      can be one of the causes of the increased ceramides content and pro apoptotic
      events during oxidative conditions and neurodegeneration. This MS study will
      support the future identification of oxidized galactosyl- and lactosylceramide
      species in sphingolipidomic studies applied to biological samples related with
      oxidative conditions. 

PMID- 26315529
TI  - Alternative Methods for Defining Osteoarthritis and the Impact on Estimating
      Prevalence in a US Population-Based Survey.
AB  - OBJECTIVE: Provide a contemporary estimate of osteoarthritis (OA) by comparing
      the accuracy and prevalence of alternative definitions of OA. METHODS: The
      Medical Expenditure Panel Survey (MEPS) household component (HC) records
      respondent-reported medical conditions as open-ended responses; professional
      coders translate these responses into International Classification of Diseases,
      Ninth Revision, Clinical Modification (ICD-9-CM) codes for the medical conditions
      files. Using these codes and other data from the MEPS-HC medical conditions
      files, we constructed 3 case definitions of OA and assessed them against medical
      provider diagnoses of ICD-9-CM 715 (osteoarthrosis and allied disorders) in a
      MEPS subsample. The 3 definitions were 1) strict = ICD-9-CM 715; 2) expanded =
      ICD-9-CM 715, 716 (other and unspecified arthropathies) OR 719 (other and
      unspecified disorders of joint); and 3) probable = strict OR expanded +
      respondent-reported prior diagnosis of OA or other arthritis excluding rheumatoid
      arthritis. RESULTS: Sensitivity and specificity of the 3 definitions,
      respectively, were 34.6% and 97.5% for strict, 73.8% and 90.5% for expanded, and
      62.9% and 93.5% for probable. CONCLUSION: The strict definition for OA (ICD-9-CM
      715) excludes many individuals with OA. The probable definition of OA has the
      optimal combination of sensitivity and specificity relative to the 2 other MEPS
      based definitions and yields a national annual estimate of 30.8 million adults
      with OA (13.4% of US adult population) for 2008-2011.

PMID- 26315530
TI  - Spatiotemporal dynamics of counterpropagating Airy beams.
AB  - We analyse theoretically the spatiotemporal dynamics of two incoherent
      counterpropagating Airy beams interacting in a photorefractive crystal under
      focusing conditions. For a large enough nonlinearity strength the interaction
      between the two Airy beams leads to light-induced waveguiding. The stability of
      the waveguide is determined by the crystal length, the nonlinearity strength and
      the beam's intensities and is improved when comparing to the situation using
      Gaussian beams. We further identify the threshold above which the waveguide is no
      longer static but evolves dynamically either time-periodically or even
      chaotically. Above the stability threshold, each Airy-soliton moves erratically
      between privileged output positions that correspond to the spatial positions of
      the lobes of the counterpropagating Airy beam. These results suggest new ways of
      creating dynamically varying waveguides, optical logic gates and chaos-based
      computing. 

PMID- 26315531
TI  - Hypertension in Pregnancy and Future Cardiovascular Event Risk in Siblings.
AB  - Hypertension in pregnancy is a risk factor for future hypertension and
      cardiovascular disease. This may reflect an underlying familial predisposition or
      persistent damage caused by the hypertensive pregnancy. We sought to isolate the
      effect of hypertension in pregnancy by comparing the risk of hypertension and
      cardiovascular disease in women who had hypertension in pregnancy and their
      sisters who did not using the dataset from the Genetic Epidemiology Network of
      Arteriopathy study, which examined the genetics of hypertension in white, black,
      and Hispanic siblings. This analysis included all sibships with at least one
      parous woman and at least one other sibling. After gathering demographic and
      pregnancy data, BP and serum analytes were measured. Disease-free survival was
      examined using Kaplan-Meier curves and Cox proportional hazards regression.
      Compared with their sisters who did not have hypertension in pregnancy, women who
      had hypertension in pregnancy were more likely to develop new onset hypertension
      later in life, after adjusting for body mass index and diabetes (hazard ratio
      1.75, 95% confidence interval 1.27-2.42). A sibling history of hypertension in
      pregnancy was also associated with an increased risk of hypertension in brothers
      and unaffected sisters, whereas an increased risk of cardiovascular events was
      observed in brothers only. These results suggest familial factors contribute to
      the increased risk of future hypertension in women who had hypertension in
      pregnancy. Further studies are needed to clarify the potential role of
      nonfamilial factors. Furthermore, a sibling history of hypertension in pregnancy
      may be a novel familial risk factor for future hypertension. 

PMID- 26315532
TI  - Double-Negative alphabeta T Cells Are Early Responders to AKI and Are Found in
      Human Kidney.
AB  - Ischemia-reperfusion injury (IRI) is a major cause of AKI, and previous studies
      established important roles for conventional CD4(+) T cells, natural killer T
      cells, and CD4(+)CD25(+)FoxP3(+) Tregs in AKI pathogenesis. We recently
      identified CD4(-)CD8(-) (double-negative; DN) T cells as an important subset of
      alphabeta T cell receptor-positive cells residing in mouse kidney. However,
      little is known about the pathophysiologic functions of kidney DN T cells. In
      this study, we phenotypically and functionally characterized murine kidney DN T
      cells in the steady state and in response to IRI. Unlike CD4(+) and CD8(+) T
      cells, DN T cells in the steady state expressed high levels of CD69, CD28, and
      CD40L; differentially expressed IL-27 and IL-10 anti-inflammatory cytokines;
      spontaneously proliferated at a very high rate; and suppressed in vitro
      proliferation of activated CD4(+) T cells. Within the first 3-24 hours after IRI,
      kidney DN T cells expanded significantly and upregulated expression of IL-10. In
      adoptive transfer experiments, DN T cells significantly protected recipients from
      AKI by an IL-10-dependent mechanism. DN T cells also made up a large fraction of
      the T cell compartment in human kidneys. Our results indicate that DN T cells are
      an important subset of the resident alphabeta(+) T cell population in the
      mammalian kidney and are early responders to AKI that have anti-inflammatory
      properties.

PMID- 26315533
TI  - Peripheral blood proinflammatory response in women during menstrual cycle and
      endometriosis.
AB  - The aim of this study was to evaluate differences in levels of serum and monocyte
      derived interleukin (IL)-1, IL-6 and neopterin (NPT) in women with normal or
      abnormal menstrual cycles and women with endometriosis. The women participating
      in this study were divided into 4 groups: 25 women with normal menstrual cycle;
      25 women taking oral contraception (OC); 20 postmenopausal women and 25
      endometriosis patients. IL-1beta, IL-6 and NPT levels in serum and monocyte
      culture media were measured with ELISA methods. The data collected showed the
      lowest serum NPT levels in women with follicular menstrual cycles. The levels of
      both types of interleukins in serum were the lowest in women using OC. In
      contrast, the highest concentrations of all cytokines were found in the serum of
      women with endometriosis. The lowest monocyte activity was observed in women with
      a follicular menstrual cycle phase and the highest in endometriosis. Monocytes
      from women using OC secreted similar amounts of cytokines to the cells during the
      follicular menstrual cycle phase. Changes occurring at the time of contraception,
      after menopause and during endometriosis, are followed by changed proinflammatory
      monocyte activity, which is associated with different secretion of cytokines. OC
      can inhibit inflammatory monocyte properties. Lower serum concentration of
      cytokines compared to cell secretion may suggest some control mechanisms of
      monocyte activity. 

PMID- 26315534
TI  - Endogenous and pharmacologic targeting of the STING pathway in cancer
      immunotherapy.

PMID- 26315536
TI  - Preventing depression and anxiety in young people: a review of the joint efficacy
      of universal, selective and indicated prevention.
AB  - Depression and anxiety (internalizing disorders) are the largest contributors to
      the non-fatal health burden among young people. This is the first meta-analysis
      to examine the joint efficacy of universal, selective, and indicated preventive
      interventions upon both depression and anxiety among children and adolescents (5
      18 years) while accounting for their co-morbidity. We conducted a systematic
      review of reviews in Medline, PsycINFO and the Cochrane Library of Systematic
      Reviews, from 1980 to August 2014. Multivariate meta-analysis examined the
      efficacy of preventive interventions on depression and anxiety outcomes
      separately, and the joint efficacy on both disorders combined. Meta-regressions
      examined heterogeneity of effect according to a range of study variables.
      Outcomes were relative risks (RR) for disorder, and standardized mean differences
      (Cohen's d) for symptoms. One hundred and forty-six randomized controlled trials
      (46 072 participants) evaluated universal (children with no identified risk, n =
      54) selective (population subgroups of children who have an increased risk of
      developing internalizing disorders due to shared risk factors, n = 45) and
      indicated prevention (children with minimal but detectable symptoms of an
      internalizing disorder, n = 47), mostly using psychological-only strategies (n =
      105). Reductions in internalizing disorder onset occurred up to 9 months post
      intervention, whether universal [RR 0.47, 95% confidence interval (CI) 0.37
      0.60], selective (RR 0.61, 95% CI 0.43-0.85) or indicated (RR 0.48, 95% CI 0.29
      0.78). Reductions in internalizing symptoms occurred up to 12 months post
      intervention for universal prevention; however, reductions only occurred in the
      shorter term for selective and indicated prevention. Universal, selective and
      indicated prevention interventions are efficacious in reducing internalizing
      disorders and symptoms in the short term. They might be considered as repeated
      exposures in school settings across childhood and adolescence. (PROSPERO
      registration: CRD42014013990.). 

PMID- 26315535
TI  - miR-9-5p suppresses pro-fibrogenic transformation of fibroblasts and prevents
      organ fibrosis by targeting NOX4 and TGFBR2.
AB  - Uncontrolled extracellular matrix (ECM) production by fibroblasts in response to
      injury contributes to fibrotic diseases, including idiopathic pulmonary fibrosis
      (IPF). Reactive oxygen species (ROS) generation is involved in the pathogenesis
      of IPF. Transforming growth factor-beta1 (TGF-beta1) stimulates the production of
      NADPH oxidase 4 (NOX4)-dependent ROS, promoting lung fibrosis (LF). Dysregulation
      of microRNAs (miRNAs) has been shown to contribute to LF. To identify miRNAs
      involved in redox regulation relevant for IPF, we performed arrays in human lung
      fibroblasts exposed to ROS. miR-9-5p was selected as the best candidate and we
      demonstrate its inhibitory effect on TGF-beta receptor type II (TGFBR2) and NOX4
      expression. Increased expression of miR-9-5p abrogates TGF-beta1-dependent
      myofibroblast phenotypic transformation. In the mouse model of bleomycin-induced
      LF, miR-9-5p dramatically reduces fibrogenesis and inhibition of miR-9-5p and
      prevents its anti-fibrotic effect both in vitro and in vivo. In lung specimens
      from patients with IPF, high levels of miR-9-5p are found. In omentum-derived
      mesothelial cells (MCs) from patients subjected to peritoneal dialysis (PD), miR
      9-5p also inhibits mesothelial to myofibroblast transformation. We propose that
      TGF-beta1 induces miR-9-5p expression as a self-limiting homeostatic response.

PMID- 26315537
TI  - Diet and nutrient balance of red panda in Nepal.
AB  - We identified the winter plant species consumed by red panda in the Dhorpatan
      Hunting Reserve of eastern Nepal and compared this to the early-summer diet which
      was determined previously by Panthi et al. (2012). In addition, we estimated the
      proximate nutritional content of the leaves identified in red panda diet for both
      seasons, and we used nutritional geometry to explore macronutrient balance of
      leaves from the two different sampling periods. We identified six different
      plants in winter scats, which were the same as found in the previously determined
      early-summer diet. Arundinaria spp. bamboos were the main species found (82.1 %
      relative frequency), followed by Acer spp. (6.3 %), Betula utilis (4.6 %),
      Quercus semicarpifolia (3.7 %), Berberis spp. (1.3 %), and lichens (1.0 %),
      leaving 2.0 % unidentified. Geometric analysis suggested that the macronutrient
      balance of seasonal diets were similar in nutrient balance to the most frequently
      consumed Arundinaria spp. Differences in macronutrient balance may indicate
      seasonal nutrient preferences, such as increased carbohydrate intake in winter
      for thermogenesis, and increased protein and lipid intake in early summer to
      support reproduction and lactation; however, these differences may also indicate
      differences in resource availability. Habitat conserved for red panda in the
      region should include sufficient Arundinaria spp. as well as lesser consumed
      plants which may serve as complimentary foods.

PMID- 26315538
TI  - Spatial and temporal expression of zebrafish glutathione peroxidase 4 a and b
      genes during early embryo development.
AB  - Antioxidant cellular mechanisms are essential for cell redox homeostasis during
      animal development and in adult life. Previous in situ hybridization analyses of
      antioxidant enzymes in zebrafish have indicated that they are ubiquitously
      expressed. However, spatial information about the protein distribution of these
      enzymes is not available. Zebrafish embryos are particularly suitable for this
      type of analysis due to their small size, transparency and fast development. The
      main objective of the present work was to analyze the spatial and temporal gene
      expression pattern of the two reported zebrafish glutathione peroxidase 4 (GPx4)
      genes during the first day of zebrafish embryo development. We found that the
      gpx4b gene shows maternal and zygotic gene expression in the embryo proper
      compared to gpx4a that showed zygotic gene expression in the periderm covering
      the yolk cell only. Following, we performed a GPx4 protein immunolocalization
      analysis during the first 24-h of development. The detection of this protein
      suggests that the antibody recognizes GPx4b in the embryo proper during the first
      24 h of development and GPx4a at the periderm covering the yolk cell after 14
      somite stage. Throughout early cleavages, GPx4 was located in blastomeres and was
      less abundant at the cleavage furrow. Later, from the 128-cell to 512-cell
      stages, GPx4 remained in the cytoplasm but gradually increased in the nuclei,
      beginning in marginal blastomeres and extending the nuclear localization to all
      blastomeres. During epiboly progression, GPx4b was found in blastoderm cells and
      was excluded from the yolk cell. After 24 h of development, GPx4b was present in
      the myotomes particularly in the slow muscle fibers, and was excluded from the
      myosepta. These results highlight the dynamics of the GPx4 localization pattern
      and suggest its potential participation in fundamental developmental processes.

PMID- 26315539
TI  - Proportions of CD4+, CD8+ and B cell subsets are not affected by exposure to HIV
      or to Cotrimoxazole prophylaxis in Malawian HIV-uninfected but exposed children.
AB  - BACKGROUND: As a result of successful PMTCT programs, children born from HIV
      infected mothers are now effectively protected from contracting the infection.
      However, it is not well known whether in utero exposure to the virus and the
      subsequent exposure to Cotrimoxazole (CTX) prophylaxis affect the cell mediated
      immune system of the children. This observational prospective study was aimed at
      determining how CD4(+) T, CD8(+) T and B cell subsets varied in HIV-exposed but
      uninfected (HEU) children at different ages. METHODS: We recruited HEU and HIV
      unexposed and uninfected (HUU) children from 6 months of age and followed them up
      until they were 18 months old. HEU children received daily CTX prophylaxis
      beginning at 6 weeks of age until when 12 months of age. Venous blood samples
      were collected 6 monthly and analysed for different subsets of CD8(+) T, B cells
      and totalCD4(+) T cells. RESULTS: At 6 months of age, HEU children had a lower
      percentage of total CD4(+) T cells compared to HUU children and a lower
      proportion of naive CD8(+) T cells but higher percentage of effector memory
      CD8(+) T cells compared to HUU children. HEU and HUU children had similar
      proportions of all B cell subsets at all ages. CONCLUSIONS: The study showed that
      the subtle variations in CD4(+) and CD8(+) T cell subsets observed at 6 months do
      not last beyond 12 months of age, suggesting that HEU children have a robust cell
      mediated immune system during first year of life. TRIAL REGISTRATION: This
      article report is not based on results of a controlled health-care intervention.

PMID- 26315540
TI  - Type I Interferon Inhibition of MicroRNA-146a Maturation Through Up-Regulation of
      Monocyte Chemotactic Protein-Induced Protein 1 in Systemic Lupus Erythematosus.
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE) is characterized by the
      uncontrolled production of inflammatory cytokines, among which type I interferon
      (IFN) is recognized as a crucial pathogenic factor. The expression of microRNA
      146a (miR-146a) is reduced in the white blood cells of SLE patients and accounts
      for their overactivated inflammatory responses. However, the mechanism of the
      reduction of miR-146a is still not fully understood. This study was undertaken to
      test whether the key pathogenic cytokine, type I IFN, is responsible for the
      dysregulation of miR-146a in SLE. METHODS: Gene and protein expression was
      measured in all cells by reverse transcription-quantitative polymerase chain
      reaction, Northern blotting, or Western blotting. In THP-1 cells, expression of
      monocyte chemotactic protein-induced protein 1 (MCPIP-1) was knocked down with a
      lentivirus encoding a short hairpin RNA targeting MCPIP1. The cells were
      pretreated with type I IFN and assessed for gene expression levels of miR-146a.
      White blood cells from patients with SLE were analyzed for the expression of the
      IFN-inducible genes MCPIP1 and miR-146a, and the gene expression data were
      compared for correlation. RESULTS: Pretreatment of THP-1 cells with type I IFN
      attenuated the induction of miR-146a posttranscriptionally, by down-regulating
      the expression of pre-miR-146a but not pri-miR-146a or its original unspliced
      transcript. Expression of MCPIP-1, which was enhanced by type I IFN, was found to
      be responsible for the inhibition of miR-146a. In white blood cells from patients
      with SLE, MCPIP1 expression was elevated, and its expression correlated
      positively with the IFN score and negatively with the miR-146a transcript level.
      CONCLUSION: Type I IFN inhibits the maturation of miR-146a through the up
      regulation of MCPIP-1, and thus contributes to the uncontrolled inflammation and
      excessive inflammatory gene expression in SLE.

PMID- 26315541
TI  - MicroRNA-424 inhibits Akt3/E2F3 axis and tumor growth in hepatocellular
      carcinoma.
AB  - By comparing the expression profiles of miRNAs in different subtypes of HCC, we
      identified miR-424 as a HCC related miRNA. We found that the expression of miR
      424 was significantly decreased in HCC tissues and six liver cancer cell lines.
      Significantly, its expression levels were correlated with tumor size, multiple
      nodules, vein invasion, TNM stage and overall survival of HCC. We showed that up
      regulated miR-424 suppressed HCC cell proliferation in vivo and in vitro. Multi
      pathway reporter arrays suggested that miR-424 suppressed the pRb-E2F pathway.
      Consistently, Akt3 and E2F3 were identified as the targets of miR-424 as
      evidenced by that ectopic miR-424 expression suppressed Akt3 and E2F3
      expressions. Silencing Akt3 and E2F3 by siRNA pheno-copied the effect of ectopic
      miR-424 on HCC growth. Whereas, overexpression of Akt3 and E2F3 attenuated the
      effect of miR-424 on HCC growth. Together, our data demonstrated a tumor
      suppressor role for miR-424 in HCC development and progression with therapeutic
      implications. The strong correlation of miR-424 expression with HCC patient
      survival suggests that miR-424 could be a valuable biomarker for HCC prognosis. 

PMID- 26315542
TI  - Cutting efficiency of diamond burs operated with electric high-speed dental
      handpiece on zirconia.
AB  - Zirconia-based dental restorations are becoming used more commonly. However,
      limited attention has been given to the difficulties experienced, concerning
      cutting, in removing the restorations when needed. The aim of the present study
      was to compare the cutting efficiency of diamond burs, operated using an electric
      high-speed dental handpiece, on zirconia (Zir) with those on lithium disilicate
      glass-ceramic (LD) and leucite glass-ceramic (L). In addition, evaluation of the
      cutting efficiency of diamond burs on Zir of different thicknesses was performed.
      Specimens of Zir were prepared with thicknesses of 0.5, 1.0, 2.0, and 4.0 mm, and
      specimens of LD and L were prepared with a thickness of 1.0 mm. Cutting tests
      were performed using diamond burs with super coarse (SC) and coarse (C) grains.
      The handpiece was operated at 150,000 rpm with a cutting force of 0.9 N. The
      results demonstrated that cutting of Zir took about 1.5- and 7-fold longer than
      cutting of LD and L, respectively. The SC grains showed significantly higher
      cutting efficiency on Zir than the C grains. However, when the thickness of Zir
      increased, the cutting depth was significantly decreased. As it is suggested that
      cutting of zirconia is time consuming, this should be taken into consideration in
      advance when working with zirconia restorations.

PMID- 26315544
TI  - The Role of Ownership in Hospice Care: Commentary on Teno et al.

PMID- 26315545
TI  - Cytomorphologic and Flow Cytometric Analysis of Cerebrospinal Fluid with T-Cell
      Lymphoma Involvement: A Retrospective Study of Rare Cases.
AB  - OBJECTIVE: To compare the efficacy of conventional cytomorphologic analysis and
      flow cytometry (FC) in the diagnosis of T-cell lymphoma in the cerebrospinal
      fluid (CSF). STUDY DESIGN: We performed a retrospective review of CSF samples
      from 2002 to 2012 that showed involvement of a T-cell lymphoma, either by
      cytomorphologic analysis and/or FC. Patients' demographics, clinical history and
      follow-up were assessed. RESULTS: Thirty-nine CSF samples were identified from 9
      patients. A definitive diagnosis of T-cell lymphoma involvement was made by
      cytomorphologic analysis and FC in 6 (15.4%) and 39 (100.0%) specimens,
      respectively. In specimens with definitive cytopathologic diagnoses, the
      cytomorphologic features included increased cellularity, a monotonous lymphoid
      population and large, atypical lymphoid cells. Considering cytomorphologic
      features only, 9 specimens demonstrated atypical lymphocytes not fulfilling the
      criteria for malignancy, and 24 specimens were negative for malignancy.
      CONCLUSIONS: CSF with T-cell lymphoma involvement may yield paucicellular or
      acellular specimens depending on the volume of the CSF, the time interval between
      specimen collection and specimen processing and the application of preservative
      to CSF. The rate of detection of T-cell lymphoma in the CSF by FC is
      unequivocally higher than by cytomorphologic analysis. Careful attention to
      clinical history is crucial, as FC testing may be tailored to evaluate for T-cell
      lymphoproliferative disorders in limited samples.

PMID- 26315546
TI  - Expectations of Medical Student Neuroradiology Education: A Survey of Practicing
      Neuroradiologists and Neurologists.
AB  - The purpose of this study is to evaluate which neuroradiological diseases
      neuroradiologists and neurologists believe medical students should be exposed to
      during their neuroradiology rotation. Members of the American Society of
      Neuroradiology (ASNR) and the American Academy of Neurology (AAN) were surveyed.
      Respondents were presented 32 diseases with neuroimaging findings and asked which
      ones medical students should be exposed to during a neuroradiology rotation.
      Using a 50% response threshold per disease entity, results were tabulated into 3
      groups: diagnoses that (1) more than 50% of neuroradiologists and neurologists
      felt medical students should see radiologically by rotation completion, (2) less
      than 50% of respondents in both the groups felt were important, and (3) both the
      groups disagree are important. Both the groups thought medical students should be
      exposed to imaging of intraparenchymal hemorrhage (ASNR = 80.4% vs AAN = 84.3%; P
      = 0.346) and subarachnoid hemorrhage (ASNR = 74% vs AAN = 78%; P = 0.394). Both
      the groups (>50%) thought subdural hematoma, acute ischemic stroke, epidural
      hematoma, and spinal cord compression are important. Conditions such as spine
      fractures, nonacute stroke, arteriovenous malformation, and ear-nose-throat
      pathology showed varied results between both the groups. Varying degrees of
      similarity and differences exist between the expectations of neuroradiologists
      and neurologists regarding medical student neuroradiology education, presenting a
      positive opportunity for greater consensus, dialogue, and joint curriculum
      formation. 

PMID- 26315547
TI  - Risk factors for delay in age-appropriate vaccinations among Gambian children.
AB  - BACKGROUND: Vaccination has been shown to reduce mortality and morbidity due to
      vaccine-preventable diseases. However, these diseases are still responsible for
      majority of childhood deaths worldwide especially in the developing countries.
      This may be due to low vaccine coverage or delay in receipt of age-appropriate
      vaccines. We studied the timeliness of routine vaccinations among children aged
      12-59 months attending infant welfare clinics in semi-urban areas of The Gambia,
      a country with high vaccine coverage. METHODS: A cross-sectional survey was
      conducted in four health centres in the Western Region of the Gambia. Vaccination
      dates were obtained from health cards and timeliness assessed based on the
      recommended age ranges for BCG (birth-8 weeks), Diphtheria-Pertussis-Tetanus (6
      weeks-4 months; 10 weeks-5 months; 14 weeks-6 months) and measles vaccines (38
      weeks-12 months). Risk factors for delay in age-appropriate vaccinations were
      determined using logistic regression. Analysis was limited to BCG, third dose of
      Diphtheria-Pertussis -Tetanus (DPT3) and measles vaccines. RESULTS: Vaccination
      records of 1154 children were studied. Overall, 63.3% (95 % CI 60.6-66.1%) of the
      children had a delay in the recommended time to receiving at least one of the
      studied vaccines. The proportion of children with delayed vaccinations increased
      from BCG [5.8% (95 % CI 4.5-7.0%)] to DPT3 [60.4% (95 % CI 57.9%-63.0%)] but was
      comparatively low for the measles vaccine [10.8% (95 % CI 9.1%-12.5%)]. Mothers
      of affected children gave reasons for the delay, and their profile correlated
      with type of occupation, place of birth and mode of transportation to the health
      facilities. CONCLUSION: Despite high vaccination coverage reported in The Gambia,
      a significant proportion of the children's vaccines were delayed for reasons
      related to health services as well as profile of mothers. These findings are
      likely to obtain in several countries and should be addressed by programme
      managers in order to improve and optimize the impact of the immunization coverage
      rates.

PMID- 26315550
TI  - Polarization Transfer from Ligands Hyperpolarized by Dissolution Dynamic Nuclear
      Polarization for Screening in Drug Discovery.
AB  - Nuclear magnetic resonance (NMR) spectroscopy is a valuable technique for ligand
      screening, because it exhibits high specificity toward chemical structure and
      interactions. Dissolution dynamic nuclear polarization (DNP) is a recent advance
      in NMR methodology that enables the creation of non-equilibrium spin states,
      which can dramatically increase NMR sensitivity. Here, the transfer of such spin
      polarization from hyperpolarized ligand to protein is observed. Mixing
      hyperpolarized benzamidine with the serine protease trypsin, a "fingerprint" of
      enhanced protein signals is observed, which shows a different intensity profile
      than the equilibrium NMR spectrum of the protein, but coincides closely to the
      frequency profile of a saturation transfer difference (STD) NMR experiment. The
      DNP experiment benefits from hyperpolarization and enables observation of all
      frequencies in a single, rapid experiment. Based on these merits, it is an
      interesting alternative to the widely used STD experiment for identification of
      protein-ligand interactions. 

PMID- 26315551
TI  - Motorcycle-related hospitalization of adolescents in a Level I trauma center in
      southern Taiwan: a cross-sectional study.
AB  - BACKGROUND: The aim of this study was to investigate and compare the injury
      pattern, mechanisms, severity, and mortality of adolescents and adults
      hospitalized for treatment of trauma following motorcycle accidents in a Level I
      trauma center. METHODS: Detailed data regarding patients aged 13-19 years
      (adolescents) and aged 30-50 years (adults) who had sustained trauma due to a
      motorcycle accident were retrieved from the Trauma Registry System between
      January 1, 2009 and December 31, 2012. The Pearson's chi-squared test, Fisher's
      exact test, or the independent Student's t-test were performed to compare the
      adolescent and adult motorcyclists and to compare the motorcycle drivers and
      motorcycle pillion. RESULTS: Analysis of Abbreviated Injury Scale (AIS) scores
      revealed that the adolescent patients had sustained higher rates of facial,
      abdominal, and hepatic injury and of cranial, mandibular, and femoral fracture
      but lower rates of thorax and extremity injury; hemothorax; and rib, scapular,
      clavicle, and humeral fracture compared to the adults. No significant differences
      were found between the adolescents and adults regarding Injury Severity Score
      (ISS), New Injury Severity Score (NISS), Trauma-Injury Severity Score (TRISS),
      mortality, length of hospital stay, or intensive care unit (ICU) admission rate.
      A significantly greater percentage of adolescents compared to adults were found
      not to have worn a helmet. Motorcycle riders who had not worn a helmet were found
      to have a significantly lower first Glasgow Coma Scale (GCS) score, and a
      significantly higher percentage was found to present with unconscious status,
      head and neck injury, and cranial fracture compared to those who had worn a
      helmet. CONCLUSION: Adolescent motorcycle riders comprise a major population of
      patients hospitalized for treatment of trauma. This population tends to present
      with a higher injury severity compared to other hospitalized trauma patients and
      a bodily injury pattern differing from that of adult motorcycle riders,
      indicating the need to emphasize use of protective equipment, especially helmets,
      to reduce their rate and severity of injury.

PMID- 26315552
TI  - Two novel variants on 13q22.1 are associated with risk of esophageal squamous
      cell carcinoma.
AB  - BACKGROUND: Chromosome 13q22.1 has previously been identified to be a
      susceptibility locus for pancreatic cancer in Chinese and European ancestry
      populations. This pleiotropy study aimed to identify novel variants in this
      region associated with susceptibility to different types of human cancer. METHOD:
      To fine-map the 13q22.1 region, imputation analyses were conducted on the basis
      of the GWAS data of 2,031 esophageal squamous cell cancer (ESCC) cases and 2,044
      controls and 5,930 SNPs (625 directly genotyped and 5,305 well imputed).
      Promising associations were then examined in ESCC (4,146 cases and 4,135
      controls), gastric cardia cancer (1,894 cases and 1,912 controls), noncardia
      gastric cancer (1,007 cases and 2,243 controls), and colorectal cancer (1,111
      cases and 1,138 controls). Fine mapping and biochemical analyses were further
      performed to elucidate the potential function of novel variants. RESULTS: Two
      novel variants, rs1924966 and rs115797771, were associated with ESCC risk (P =
      1.37 * 10(-10) and P = 2.32 * 10(-10), respectively) and were also associated
      with risk of gastric cardia cancer (P = 0.0003 and P = 0.0018, respectively) but
      not gastric cancer and colorectal cancer. Fine-mapping revealed another SNP,
      rs58090485, in strong linkage disequilibrium with rs115797771 (r(2) = 0.94).
      Functional analysis showed that this SNP disturbs a transcriptional repressor
      binding to the promoter region of KLF5, which might result in high constitutional
      expression of KLF5. CONCLUSIONS: These results demonstrate that variants mapped
      on 13q22.1 are associated with the risk of different types of cancer. IMPACT:
      13q22.1 might serve as a biomarker for the identification of individuals at risk
      for ESCC and gastric cardia cancer.

PMID- 26315553
TI  - Octreotide long-acting repeatable among elderly patients with neuroendocrine
      tumors: a survival analysis of SEER-Medicare data.
AB  - BACKGROUND: Octreotide long-acting repeatable (LAR) is approved in the United
      States for the management of carcinoid syndromes among patients with
      neuroendocrine tumors (NET). The objective of our study is to evaluate the impact
      of octreotide LAR on overall survival (OS), as it has not been established.
      METHODS: NET patients of 65 years and older diagnosed between January 1999 and
      December 2009 were identified from the SEER-Medicare database. We compared the OS
      of NET patients who started octreotide LAR within 12 months of diagnosis with
      those who did not receive it during the same period. We conducted Kaplan-Meier
      estimations and Cox proportional hazard models to examine the association between
      octreotide LAR and OS. RESULTS: Among 1,176 distant stage patients, 233 (20%)
      received octreotide LAR within 12 months of diagnosis, compared with 2% (96 in
      5,764) of local/regional stage patients. Median OS for patients who started
      octreotide LAR within 12 months was 35.22 months [95% confidence interval (CI),
      27.96-47.77], longer than those who did not receive it (19.15 months; 95% CI,
      16.36-22.80; P < 0.0001). Multivariate analysis showed that octreotide LAR was
      associated with significant survival improvement for distant stage patients (HR,
      0.68; P < 0.001) and in the subgroups with (HR, 0.65; P, 0.003) and without (HR,
      0.55; P, 0.002) carcinoid syndrome. No survival benefit was found among
      local/regional stage patients. CONCLUSION: This population-based study suggests
      potential survival benefits of octreotide LAR among elderly distant stage NET
      patients, both with or without carcinoid syndrome. IMPACT: The study provides
      population-based evidence of a positive association between octreotide LAR and
      overall survival among elderly distant stage NET patients.

PMID- 26315554
TI  - The effect of change in body mass index on volumetric measures of mammographic
      density.
AB  - BACKGROUND: Understanding how changes in body mass index (BMI) relate to changes
      in mammographic density is necessary to evaluate adjustment for BMI gain/loss in
      studies of change in density and breast cancer risk. Increase in BMI has been
      associated with a decrease in percent density, but the effect on change in
      absolute dense area or volume is unclear. METHODS: We examined the association
      between change in BMI and change in volumetric breast density among 24,556 women
      in the San Francisco Mammography Registry from 2007 to 2013. Height and weight
      were self-reported at the time of mammography. Breast density was assessed using
      single x-ray absorptiometry measurements. Cross-sectional and longitudinal
      associations between BMI and dense volume (DV), non-dense volume (NDV), and
      percent dense volume (PDV) were assessed using multivariable linear regression
      models, adjusted for demographics, risk factors, and reproductive history.
      RESULTS: In cross-sectional analysis, BMI was positively associated with DV
      [beta, 2.95 cm(3); 95% confidence interval (CI), 2.69-3.21] and inversely
      associated with PDV (beta, -2.03%; 95% CI, -2.09, -1.98). In contrast, increasing
      BMI was longitudinally associated with a decrease in both DV (beta, -1.01 cm(3);
      95% CI, -1.59, -0.42) and PDV (beta, -1.17%; 95% CI, -1.31, -1.04). These
      findings were consistent for both pre- and postmenopausal women. CONCLUSION: Our
      findings support an inverse association between change in BMI and change in PDV.
      The association between increasing BMI and decreasing DV requires confirmation.
      IMPACT: Longitudinal studies of PDV and breast cancer risk, or those using PDV as
      an indicator of breast cancer risk, should evaluate adjustment for change in BMI.

PMID- 26315555
TI  - Aspirin use and risk of breast cancer: systematic review and meta-analysis of
      observational studies.
AB  - Previous studies concerning the association between aspirin use and breast cancer
      risk yielded inconsistent results. We aimed to investigate the association by
      meta-analysis. PubMed and EMBASE were searched for relevant studies. We
      calculated the summary relative risks (RR) and 95% confidence intervals (CI)
      using random-effects models. Seventeen cohort studies and 15 case-control studies
      were included. The overall result showed that aspirin use decreased risk of
      breast cancer (RR, 0.90; 95% CI, 0.85-0.95). However, there was evidence of
      publication bias and heterogeneity and the association disappeared after
      correction using the trim-and-fill method. When stratified by study design, a
      significant benefit for aspirin users was only found in population-based and
      hospital-based case-control studies but not in cohort or nest case-control
      studies. Further subgroup analyses showed that aspirin use could decrease risk of
      in situ breast tumors or hormone receptor-positive tumors and reduce risk of
      breast cancer in postmenopausal women. Aspirin use may not affect overall risk of
      breast cancer, but decrease risk of in situ breast tumors or hormone receptor
      positive tumors and reduce risk of breast cancer in postmenopausal women.
      Considering between-study significant heterogeneity and publication bias,
      confirmation in future studies is also essential.

PMID- 26315556
TI  - Myricetin inhibits proliferation of cisplatin-resistant cancer cells through a
      p53-dependent apoptotic pathway.
AB  - Cisplatin is a commonly used drug for cancer treatment by crosslinking DNA,
      leading to apoptosis of cancer cells, resistance to cisplatin treatment often
      occurs, leading to relapse. Therefore, there is a need for the development of
      more effective treatment strategies that can overcome chemoresistance. Myricetin
      is a flavonoid from fruits and vegetables, showing anticancer activity in various
      cancer cells. In this study, we found myricetin exhibited greater cytotoxicity
      than cisplatin in two cisplatin-resistant ovarian cancer cell lines, OVCAR-3 and
      A2780/CP70, and it was less cytotoxic to the normal ovarian cell line IOSE-364.
      Myricetin selectively induced apoptosis in both cisplatin-resistant cancer cell
      lines, but did not induce apoptosis in the normal ovarian cell line. It induced
      both Bcl-2 family-dependent intrinsic and DR5 dependent extrinsic apoptosis in
      OVCAR-3 cells. P53, a multifunctional tumor suppressor, regulated apoptosis in
      OVCAR-3 cells through a Bcl-2 family protein-dependent pathway. Myricetin did not
      induce cell cycle arrest in either ovarian cancer cell line. Because of its
      potency and selectivity against cisplatin-resistant cancer cells, myricetin could
      potentially be used to overcome cancer chemoresistance against platinum-based
      therapy. 

PMID- 26315557
TI  - Main causes and risk factors for hospitalisation in patients with primary
      Sjogren's syndrome.
AB  - OBJECTIVES: To identify the causes and risk factors for hospitalisation in
      primary Sjogren's syndrome (pSS). METHODS: We included 170 pSS patients who
      regularly attended our Institution (2000-2013) and retrospectively collected
      demographic, clinical (glandular and extraglandular features) and serological
      (anti-Ro/SSA, anti-La/SSB, RF, low C3 or C4 and immunoglobulin levels) data. If
      they were hospitalised, a rheumatologist determined the primary cause. We
      registered the length of hospitalisation, need for Intensive Care Unit (ICU)
      admission, number of hospitalisations and death. The Disease Damage Index (SSDDI)
      (excluding the oral and ocular items) and the Charlson comorbidity Index were
      assessed. We used a logistic regression analysis and multiple imputation method
      for missing data. RESULTS: Fifty-five (32%) patients were hospitalised,
      representing 111 hospitalisations (28 patients had >=1 hospital admission). The
      hospitalisation incidence density rate was 6.49/100 patient / years. The median
      length of hospital stay was 9 days (IQR 6-15), there were 7 ICU admissions and 6
      deaths. The main causes of admissions were disease activity (33.3%) and infection
      (32.4%). At the multivariate analysis, the variables associated with
      hospitalisation were hepatic involvement (OR=5.4; 95% CI 1.61-18.15; p=0.006),
      vasculitis (OR=3.8; 95% CI 1.11-13.09; p=0.03), the SSDDI (OR=1.3; 95% CI 1.01
      1.66; p=0.03) and the use of antimalarials (OR=0.08; 95% CI 0.02-0.22; p<0.001).
      CONCLUSIONS: The major causes for hospitalisation were disease activity and
      infection. Patients with hepatic involvement, vasculitis and more damage accrual
      had the highest risk for being hospitalised, while the use of antimalarials was
      protective.

PMID- 26315559
TI  - Improved charge transport and injection in a meso-superstructured solar cell by a
      tractable pre-spin-coating process.
AB  - In meso-superstructured solar cells (MSSCs), the state-of-the-art perovskite acts
      as both the light harvester and electron transporter due to its ambipolar
      properties. The inefficient pore filling and infiltration of perovskite directly
      affect the continuous distribution of perovskite in mesoporous Al2O3, resulting
      in discontinuous carrier transport in the mesoporous structure and insufficient
      electron injection to the compact TiO2 layer. Herein, we introduce a simple pre
      spin-coating process to improve the infiltration and pore filling of perovskite,
      which results in higher light absorption and enhanced electron injection, as seen
      in UV-vis spectra and photoluminescence (PL) spectra, respectively. We first
      apply time of flight (TOF) experiments to characterize charge transport in MSSCs,
      and the results reveal that more continuous charge transport pathways are formed
      with the pre-spin-coating process. This effective method, with ease of
      processing, demonstrates obviously improved photocurrents, reaching an efficiency
      as high as 14%, and promotes the application of lead halide perovskite materials
      in the photovoltaics field. 

PMID- 26315558
TI  - No association between fiber intake and prostate cancer risk: a meta-analysis of
      epidemiological studies.
AB  - BACKGROUND: The findings of epidemiologic studies on the association between
      fiber intake and prostate cancer risk remain conflicting. We aimed to examine
      this association by conducting a meta-analysis of epidemiological studies.
      METHODS: Relevant studies were identified by PubMed (1966 to March 2015) and
      Embase (1974 to March 2015) database search through March 2015. We included
      epidemiological studies that reported relative risks (RRs) or odds ratios (ORs)
      with 95% confidence intervals (CIs) for the association between dietary fiber
      intake and prostate cancer risk. Random effects models were used to calculate the
      summary risk estimates. RESULTS: For the highest compared with the lowest dietary
      fiber intake, a significantly decreased risk with prostate cancer was observed in
      case-control studies (OR = 0.82; 95% CI, 0.68-0.96), but not in cohort studies
      (RR = 0.94; 95% CI, 0.77-1.11). The combined risk estimate of all studies was
      0.89 (95% CI, 0.77, 1.01). A significant heterogeneity was observed across
      studies (p = 0.005). There was no evidence of significant publication bias based
      on Begg's funnel plot (p = 0.753) or Egger's test (p = 0.946). CONCLUSIONS: This
      meta-analysis suggests the absence of evidence for association between dietary
      fiber intake and prostate cancer risk.

PMID- 26315560
TI  - One-year progression of diabetic subclinical macular edema in eyes with mild
      nonproliferative diabetic retinopathy: location of the increase in retinal
      thickness.
AB  - PURPOSE: To characterize the 1-year progression of retinal thickness (RT)
      increase occurring in eyes with subclinical macular edema in type 2 diabetes.
      METHODS: Forty-eight type 2 diabetic eyes/patients with mild nonproliferative
      diabetic retinopathy (NPDR; levels 20 and 35 in the Early Treatment Diabetic
      Retinopathy Study) classified as presenting subclinical macular edema at baseline
      completed the 1-year follow-up period, from a sample of 194 followed in a 12
      month observational and prospective study (ClinicalTrials.gov identifier:
      NCT01145599). Automated segmentation of the retinal layers in these eyes was
      performed, followed by verification and correction by a human grader. RESULTS:
      The highest increase in RT over the 1-year follow-up period for the 48
      eyes/patients with subclinical macular edema was found in the inner nuclear layer
      (INL). Progression to clinical macular edema was also associated with increased
      thickening of other retinal layers aside from the INL. The microvascular disease
      activity shown by microaneurysm (MA) turnover >=6 was associated with progression
      from subclinical to clinical macular edema. CONCLUSIONS: Increases in RT
      occurring over a period of 1 year in diabetic eyes with mild NPDR and subclinical
      macular edema occur mainly in the INL. The development of clinical macular edema
      appears to be associated with increased thickening of other retinal layers and
      microvascular disease activity.

PMID- 26315561
TI  - Enzymatic prenylation and oxime ligation for the synthesis of stable and
      homogeneous protein-drug conjugates for targeted therapy.
AB  - Targeted therapy based on protein-drug conjugates has attracted significant
      attention owing to its high efficacy and low side effects. However, efficient and
      stable drug conjugation to a protein binder remains a challenge. Herein, a
      chemoenzymatic method to generate highly stable and homogenous drug conjugates
      with high efficiency is presented. The approach comprises the insertion of the
      CaaX sequence at the C-terminal end of the protein binder, prenylation using
      farnesyltransferase, and drug conjugation through an oxime ligation reaction.
      MMAF and an EGFR-specific repebody are used as the antitumor agent and protein
      binder, respectively. The method enables the precisely controlled synthesis of
      repebody-drug conjugates with high yield and homogeneity. The utility of this
      approach is illustrated by the notable stability of the repebody-drug conjugates
      in human plasma, negligible off-target effects, and a remarkable antitumor
      activity in vivo. The present method can be widely used for generating highly
      homogeneous and stable PDCs for targeted therapy. 

PMID- 26315562
TI  - Iatrogenic dural arteriovenous fistula after radical neck dissection for
      metastatic malignant disease: A case report.
AB  - BACKGROUND: A case of dural arteriovenous fistula (dAVF) developed after radical
      neck dissection for lymph node metastasis 2 years after oral surgery for tongue
      cancer. METHODS: The patient was asymptomatic during follow-up visits with no
      evidence of metastasis on follow-up CT scan of the neck. However, diagnostic
      angiography showed left internal carotid artery (ICA) stenosis and dAVF involving
      the posterior meningeal artery and transverse sinus at the left posterior fossa
      with cortical venous reflux (Cognard type III). They were treated with carotid
      stenting and surgery, respectively. RESULTS: The postoperative course was
      uneventful. Follow-up angiography revealed obliteration of the dAVF. CONCLUSION:
      This was a rare case of iatrogenic dAVF after surgical ligation of venous outflow
      during radical neck dissection. The surgical plan is presented along with a
      literature review regarding the development of iatrogenic dAVFs induced by direct
      surgical trauma.

PMID- 26315563
TI  - Barriers and facilitators to voluntary HIV testing uptake among communities at
      high risk of HIV exposure in Chennai, India.
AB  - In India, increasing uptake of voluntary HIV testing among 'core risk groups' is
      a national public health priority. While HIV testing uptake has been studied
      among key populations in India, limited information is available on multi-level
      barriers and facilitators to HIV testing, and experiences with free, publicly
      available testing services, among key populations. We conducted 12 focus groups
      (n = 84) and 12 key informant interviews to explore these topics among men who
      have sex with men, transgender women, cisgender female sex workers, and injecting
      drug users in the city of Chennai. We identified inter-related barriers at social
      structural, health-care system, interpersonal, and individual levels. Barriers
      included HIV stigma, marginalised-group stigma, discrimination in health-care
      settings, including government testing centres, and fears of adverse social
      consequences of testing HIV positive. Facilitators included outreach programmes
      operated by community-based/non-governmental organisations, accurate HIV
      knowledge and risk perception for HIV, and access to drug dependence treatment
      for injecting drug users. Promoting HIV testing among these key populations
      requires interventions at several levels: reducing HIV-related and marginalised
      group stigma, addressing the fears of consequences of testing, promoting pro
      testing peer and social norms, providing options for rapid and non-blood-based
      HIV tests, and ensuring non-judgmental and culturally competent HIV counselling
      and testing services.

PMID- 26315564
TI  - Two-Center Prospective, Randomized, Clinical, and Radiographic Study Comparing
      Osteotome Sinus Floor Elevation with or without Bone Graft and Simultaneous
      Implant Placement.
AB  - PURPOSE: To evaluate stability and success rate of hydrophilic nanostructured
      implants placed via osteotome sinus floor elevation (OSFE) without grafting
      material or using beta-tricalcium phosphate (beta-TCP), deproteinized bovine bone
      (DBB), or their combination, and also to assess three-dimensional volumetric
      stability of endo-sinus bone gained in the aforementioned conditions. MATERIALS
      AND METHODS: OSFE with simultaneous implant placement (10-mm long SLActive-BL(r)
      , Straumann, Basel, Switzerland) was performed. Grafting materials were randomly
      allocated to implant sites, whereas one site was left without graft. Implant
      stability was measured by resonance frequency analysis over 6 months. Implant
      success was evaluated after 2 years of loading. Volume of new endo-sinus bone was
      calculated from CBCT images using 3D Slicer(r) software. RESULTS: A total of 180
      implants were inserted into posterior maxilla of 45 patients with 6.59 +/- 0.45
      mm of residual bone height, and all remained successful after 2 years. Implant
      stability steadily increased during healing, without significant difference
      between groups (p = .658). After 2 years, endo-sinus bone significantly shrank (p
      < .001) in all groups (DBB:66.34%; beta-TCP:61.44%; new bone formed from
      coagulum: 53.02%; beta-TCP + DBB:33.47%). CONCLUSIONS: Endo-sinus bone gained
      after OSFE inevitably and significantly shrinks regardless of whether grafting
      material is applied or not. Grafting material offers no significant advantage to
      stability nor clinical success of hydrophilic and nanostructured implants placed
      simultaneously with OSFE.

PMID- 26315565
TI  - Quantify osteoarthritis gait at the doctor's office: a simple pelvis
      accelerometer based method independent from footwear and aging.

PMID- 26315566
TI  - Observation of Ultrafast Free Carrier Dynamics in Single Layer MoS2.
AB  - The dynamics of excited electrons and holes in single layer (SL) MoS2 have so far
      been difficult to disentangle from the excitons that dominate the optical
      response of this material. Here, we use time- and angle-resolved photoemission
      spectroscopy for a SL of MoS2 on a metallic substrate to directly measure the
      excited free carriers. This allows us to ascertain a direct quasiparticle band
      gap of 1.95 eV and determine an ultrafast (50 fs) extraction of excited free
      carriers via the metal in contact with the SL MoS2. This process is of key
      importance for optoelectronic applications that rely on separated free carriers
      rather than excitons. 

PMID- 26315567
TI  - The Debrisoft((r)) Monofilament Debridement Pad for Use in Acute or Chronic
      Wounds: A NICE Medical Technology Guidance.
AB  - As part of its Medical Technology Evaluation Programme, the National Institute
      for Health and Care Excellence (NICE) invited a manufacturer to provide clinical
      and economic evidence for the evaluation of the Debrisoft((r)) monofilament
      debridement pad for use in acute or chronic wounds. The University of Birmingham
      and Brunel University, acting as a consortium, was commissioned to act as an
      External Assessment Centre (EAC) for NICE, independently appraising the
      submission. This article is an overview of the original evidence submitted, the
      EAC's findings and the final NICE guidance issued. The sponsor submitted a simple
      cost analysis to estimate the costs of using Debrisoft((r)) to debride wounds
      compared with saline and gauze, hydrogel and larvae. Separate analyses were
      conducted for applications in home and applications in a clinic setting. The
      analysis took an UK National Health Service (NHS) perspective. It incorporated
      the costs of the technologies and supplementary technologies (such as dressings)
      and the costs of their application by a district nurse. The sponsor concluded
      that Debrisoft((r)) was cost saving relative to the comparators. The EAC made
      amendments to the sponsor analysis to correct for errors and to reflect
      alternative assumptions. Debrisoft((r)) remained cost saving in most analyses and
      savings ranged from L77 to L222 per patient compared with hydrogel, from L97 to
      L347 compared with saline and gauze, and from L180 to L484 compared with larvae
      depending on the assumptions included in the analysis and whether debridement
      took place in a home or clinic setting. All analyses were severely limited by the
      available data on effectiveness, in particular a lack of comparative studies and
      that the effectiveness data for the comparators came from studies reporting
      different clinical endpoints compared with Debrisoft((r)). The Medical
      Technologies Advisory Committee made a positive recommendation for adoption of
      Debrisoft((r)) and this has been published as a NICE medical technology guidance
      (MTG17). 

PMID- 26315568
TI  - Complete genome sequence of Bacillus thuringiensis HS18-1.
AB  - Bacillus thuringiensis is a spore-forming bacterium that is a type of insect
      pathogen used in the field of microbial insect control. B. thuringiensis HS18-1
      has effective toxicity for Lepidoptera and Diptera insects. It contains different
      types of parasporal crystal genes, including cry4Cb1, cry50Aa1, cry69Ab1,
      cry30Ga, cry30Ea, cry70Aa, cry71Aa, cry72Aa, cry56Aa and cry54Ba. Here, we report
      the complete genome sequence of B. thuringiensis HS18-1, which contains one
      circular gapless chromosome and nine circular plasmids. 

PMID- 26315569
TI  - Changing Epidemiology of Intestinal Obstruction in Ghana: Signs of Increasing
      Surgical Capacity and an Aging Population.
AB  - INTRODUCTION: This study aimed to describe the epidemiology and outcomes of
      intestinal obstruction at a tertiary hospital in Ghana over time. METHODS:
      Records of all patients admitted to a tertiary hospital from 2007 to 2011 with
      intestinal obstruction were identified using ICD-9 codes. Sociodemographic and
      clinical data were compared to a previously published series of intestinal
      obstructions from 1998 to 2003. Factors contributing to longer than expected
      hospital stays and death were further examined. RESULTS: Of the 230 records
      reviewed, 108 patients (47%) had obstructions due to adhesions, 50 (21%) had
      volvulus, 22 (7%) had an ileus from perforation and 14 (6%) had intussusception.
      Hernia fell from the 1st to the 8th most common cause of obstruction. Patients
      with intestinal obstruction were older in 2007-2011 compared to those presenting
      between 1998 and 2003 (p < 0.001); conditions associated with older age (e.g.,
      volvulus and neoplasia) were more frequently encountered (p < 0.001). Age over 50
      years was strong factor of in-hospital death (adjusted OR 14.2, 95% CI 1.41
      142.95). CONCLUSION: Efforts to reduce hernia backlog and expand the surgical
      workforce may have had an effect on intestinal obstruction epidemiology in Ghana.
      Increasing aging-related pathology and a higher risk of death in elderly patients
      suggest that improvement in geriatric surgical care is urgently needed.

PMID- 26315570
TI  - Whole Body MRI in the Staging of Esophageal Cancer--A Prospective Comparison with
      Whole Body 18F-FDG PET-CT.
AB  - BACKGROUND: Positron emission tomography and computed tomography (PET-CT) is
      established in the staging of esophageal cancer. In this study, an MRI protocol
      was designed to emulate the anatomical (T1-weighed (T1W) and T2W imaging) and
      functional information (diffusion-weighted imaging) provided by PET-CT. METHODS:
      In all, 49 patients with carcinoma of the esophagus underwent PET-CT and whole
      body MRI (WBMRI). WBMRI was carried out using dedicated sequences tailored to
      detect metastatic disease at each area corresponding to the anatomical coverage
      of PET-CT. Nodal status was determined from histopathology and endoscopic
      ultrasound biopsy (EUS). RESULTS: PET-CT and WBMRI identified the primary tumor
      in 46/49 (94%) and 48/49 (98%) patients, respectively. Nodal analysis in patients
      undergoing surgery (n = 18) yielded sensitivity, specificity, positive predictive
      value (PPV), negative predictive value (NPV) and accuracy of 27, 100, 100, 47 and
      56% for PET-CT, compared with 30, 100, 100, 53 and 61% for WBMRI. When nodal
      analysis included both surgical specimens and EUS criteria (n = 39), sensitivity,
      specificity, PPV, NPV and accuracy were 46, 91, 93, 40 and 59% for PET-CT
      compared with 59, 92, 94, 50 and 67% for WBMRI. Both imaging modalities
      identified distant metastases in 2 patients. CONCLUSION: WBMRI has similar
      accuracy to PET-CT in detecting the primary tumor, nodal deposits and for
      exclusion of systemic metastatic disease.

PMID- 26315572
TI  - Concise Review: Process Development Considerations for Cell Therapy.
AB  - The development of robust and well-characterized methods of production of cell
      therapies has become increasingly important as therapies advance through clinical
      trials toward approval. A successful cell therapy will be a consistent, safe, and
      effective cell product, regardless of the cell type or application. Process
      development strategies can be developed to gain efficiency while maintaining or
      improving safety and quality profiles. This review presents an introduction to
      the process development challenges of cell therapies and describes some of the
      tools available to address production issues. This article will provide a summary
      of what should be considered to efficiently advance a cellular therapy from the
      research stage through clinical trials and finally toward commercialization. The
      identification of the basic questions that affect process development is
      summarized in the target product profile, and considerations for process
      optimization are discussed. The goal is to identify potential manufacturing
      concerns early in the process so they may be addressed effectively and thus
      increase the probability that a therapy will be successful. SIGNIFICANCE: The
      present study contributes to the field of cell therapy by providing a resource
      for those transitioning a potential therapy from the research stage to clinical
      and commercial applications. It provides the necessary steps that, when followed,
      can result in successful therapies from both a clinical and commercial
      perspective.

PMID- 26315573
TI  - Introduction.
AB  - Surgery for cancers of the digestive tract is associated with a high risk of
      postoperative complications. Peri-operative nutritional support is part of the
      treatment plan, with a demonstrated positive impact on postoperative course. The
      aim of this good clinical practices guide is to help surgeons and physicians in
      improving malnutrition screening and implementing perioperative nutritional care.

PMID- 26315571
TI  - Health Span-Extending Activity of Human Amniotic Membrane- and Adipose Tissue
      Derived Stem Cells in F344 Rats.
AB  - Aging brings about the progressive decline in cognitive function and physical
      activity, along with losses of stem cell population and function. Although
      transplantation of muscle-derived stem/progenitor cells extended the health span
      and life span of progeria mice, such effects in normal animals were not
      confirmed. Human amniotic membrane-derived mesenchymal stem cells (AMMSCs) or
      adipose tissue-derived mesenchymal stem cells (ADMSCs) (1*10(6) cells per rat)
      were intravenously transplanted to 10-month-old male F344 rats once a month
      throughout their lives. Transplantation of AMMSCs and ADMSCs improved cognitive
      and physical functions of naturally aging rats, extending life span by 23.4% and
      31.3%, respectively. The stem cell therapy increased the concentration of
      acetylcholine and recovered neurotrophic factors in the brain and muscles,
      leading to restoration of microtubule-associated protein 2, cholinergic and
      dopaminergic nervous systems, microvessels, muscle mass, and antioxidative
      capacity. The results indicate that repeated transplantation of AMMSCs and ADMSCs
      elongate both health span and life span, which could be a starting point for
      antiaging or rejuvenation effects of allogeneic or autologous stem cells with
      minimum immune rejection. SIGNIFICANCE: This study demonstrates that repeated
      treatment with stem cells in normal animals has antiaging potential, extending
      health span and life span. Because antiaging and prolonged life span are issues
      currently of interest, these results are significant for readers and
      investigators.

PMID- 26315574
TI  - Immunonutrition.
AB  - Based on a grade A level of evidence, immunonutrition should be given to all
      patients operated on for a digestive cancer 5 to 7 days prior to surgery whatever
      could be the patient nutritional status. Immunonutrition should be continued in
      the postoperative phase in malnourished patients for 5 to 7 days or until
      patients are able to recover oral feeding covering at least 60% of their needs. 

PMID- 26315575
TI  - Role of the nutritional support in the ERAS programme.
AB  - ERAS programs are based on a combination of perioperative measures with a proven
      efficacy, that combined with each other lead to an enhanced recovery after
      surgery through a synergistic pathway. Such programs help to decrease
      postoperative morbidity and to reduce length of hospital stay. Beside
      immunonutrition, carbohydrate loading until 2 hours before surgery and early
      postoperative oral feeding are safe and allows enhanced recovery after surgery. 

PMID- 26315576
TI  - Perspectives.
AB  - Nutrition is part of the treatment plan. Nutritional support as well as
      immunonutrition have been shown to decrease the rate of postoperative
      complications. Many issues remain to be investigated to better understand
      underlying mechanisms and to offer patients a personalized approach. 

PMID- 26315577
TI  - Nutritional assessment and screening for malnutrition.
AB  - Malnutrition can be detected in up to 50% of patients with gastrointestinal
      cancer. Although malnutrition reflects the severity of cancer, it is important to
      underline that anticancer treatments including surgery likely increase the
      severity of malnutrition. Additionally, malnutrition is associated with an
      increased risk of perioperative morbidity and mortality. Nutritional assessment
      should be a part of pre-treatment work up of gastrointestinal cancer patients
      because nutritional support has been shown to limit the negative impact of
      malnutrition on perioperative outcome. The objective of these practice guidelines
      is to address the following questions regarding nutritional screening in
      gastrointestinal cancer patients: who should benefit from nutritional assessment,
      when nutritional assessment should be proposed, how nutritional assessment should
      be carried out and why nutritional assessment is indicated. 

PMID- 26315578
TI  - Parenteral and enteral nutritional support (excluding immunonutrition).
AB  - The surgeon plays a key role in the perioperative nutritional care in patients
      undergoing elective major digestive surgery; therefore, he has to be able to
      anticipate needs and to implement corrective measures according to
      recommendations. Pre- and postoperative enteral feeding is preferred. In patients
      without obvious undernutrition, postoperative nutritional support has to be
      initiated if patients cannot maintain oral intake above 60% of recommended intake
      for more than 7 days, and it has to be programmed if it is anticipated that the
      patient will be unable to eat for more than 7 days. Preoperative and
      postoperative nutritional support has to be offer in malnourished patients
      (grades 3 and 4). 

PMID- 26315579
TI  - Is cognitive stability in Parkinson's disease a predictable phenomenon? A 5-year
      follow-up study.
AB  - Cognitive disturbances are integral to the course of PD but the rate of cognitive
      decline remains largely unpredictable. The aim of this study was to determine the
      clinical features associated with "cognitive stability". Fifty-four patients (32
      with normal cognition and 22 featuring MCI) were recruited in 2009 and re
      evaluated after a mean time of 4.7 years; all patients underwent a detailed
      neuropsychological and clinical evaluation. A proportion of 61 % of patients (19
      with normal cognition and 14 with MCI) remained cognitive stable, whereas 39 %
      had reduced cognitive reserve. After multivariate analysis, only the preservation
      of visuo-spatial domain was predictive of cognitive stability.

PMID- 26315580
TI  - Palladium-catalyzed decarboxylative cyanation of aromatic carboxylic acids using
      [(13)C] and [(14)C]-KCN.
AB  - The development of robust and straightforward methods to efficiently label
      aromatic moieties starting from simple and convenient radio-synthetic sources
      still represents a considerable challenge. In this report, a new palladium
      catalyzed decarboxylative cyanation protocol has been described. This procedure
      utilizes [(14)C]-labeled potassium cyanide, one of the simplest and commercially
      available sources of carbon-14. Under the optimized reaction conditions, a series
      of [(13)C] and [(14)C]-aromatic nitriles were easily prepared (12-74% yield
      starting from potassium cyanide). The usefulness of this methodology is
      highlighted by a rare example of a formal two-step [(12)C]-[(14)C] carbon isotope
      exchange. The current synthetic approach may represent a promising alternative to
      traditional preparations of relevant building blocks such as labeled aromatic
      nitriles.

PMID- 26315582
TI  - Corrigendum to: Low-intensity pulsed ultrasound (LIPUS) can decrease the economic
      burden of fracture non-union.

PMID- 26315581
TI  - Open-Minded Cognition.
AB  - The present research conceptualizes open-minded cognition as a cognitive style
      that influences how individuals select and process information. An open-minded
      cognitive style is marked by willingness to consider a variety of intellectual
      perspectives, values, opinions, or beliefs-even those that contradict the
      individual's opinion. An individual's level of cognitive openness is expected to
      vary across domains (such as politics and religion). Four studies develop and
      validate a novel measure of open-minded cognition, as well as two domain-specific
      measures of religious and political open-minded cognition. Exploratory and
      confirmatory factor analysis (controlling for acquiescence bias) are used to
      develop the scales in Studies 1 to 3. Study 4 demonstrates that these scales
      possess convergent and discriminant validity. Study 5 demonstrates the scale's
      unique predictive validity using the outcome of Empathic Concern (Davis, 1980).
      Study 6 demonstrates the scale's unique predictive validity using the outcomes of
      warmth toward racial, religious, and sexual minorities. 

PMID- 26315583
TI  - Work-related perceptions and quality of life among breast cancer survivors.

PMID- 26315584
TI  - The Impact of a Non-Functional Thyroid Receptor Beta upon Triiodotironine-Induced
      Cardiac Hypertrophy in Mice.
AB  - BACKGROUND/AIMS: Thyroid hormone (TH) signalling is critical for heart function.
      The heart expresses thyroid hormone receptors (THRs); THRalpha1 and THRbeta1. We
      aimed to investigate the regulation mechanisms of the THRbeta isoform, its
      association with gene expression changes and implications for cardiac function.
      METHODS: The experiments were performed using adult male mice expressing
      TRbetaDelta337T, which contains the Delta337T mutation of the human THRB gene and
      impairs ligand binding. Cardiac function and RNA expression were studied after
      hypo-or hyperthyroidism inductions. T3-induced cardiac hypertrophy was not
      observed in TRbetaDelta337T mice, showing the fundamental role of THRbeta in
      cardiac hypertrophy. RESULTS: We identified a group of independently regulated
      THRbeta genes, which includes Adrb2, Myh7 and Hcn2 that were normally regulated
      by T3 in the TRbetaDelta337T group. However, Adrb1, Myh6 and Atp2a2 were
      regulated via THRbeta. The TRbetaDelta337T mice exhibited a contractile deficit,
      decreased ejection fraction and stroke volume, as assessed by echocardiography.
      In our model, miR-208a and miR-199a may contribute to THRbeta-mediated cardiac
      hypertrophy, as indicated by the absence of T3-regulated ventricular expression
      in TRbetaDelta337T mice. CONCLUSION: THRbeta has important role in the regulation
      of specific mRNA and miRNA in T3-induced cardiac hypertrophic growth and in the
      alteration of heart functions.

PMID- 26315585
TI  - Which patients with rheumatoid arthritis, spondyloarthritis, or juvenile
      idiopathic arthritis receive TNF-alpha antagonists in France? The CORPUS cohort
      study.
AB  - OBJECTIVES: Limited information is available about the characteristics of
      patients with active inflammatory rheumatic diseases who start TNF-alpha
      antagonist therapy. Our objective was to assess TNF-alpha antagonist prescription
      patterns in this context in France. METHODS: Between 2007 and 2009, 102
      rheumatologists, internists, and pediatricians in French university hospitals and
      private practice prospectively recruited biologics-naive patients with active
      rheumatoid arthritis (RA) (DAS28>3.2 despite methotrexate therapy),
      spondyloarthritis (SA) (BASDAI>=4 despite non-steroidal anti-inflammatory drug
      [NSAID] use), and juvenile idiopathic arthritis (JIA) (unresponsive to
      methotrexate). Patients were monitored prospectively for 1 year. RESULTS: Of the
      543 RA, 287 SA, and 53 JIA patients included in the study, 382 RA, 171 SA, and 28
      JIA patients had complete follow-up data available after 1 year. Among these
      patients, 110/382 (28.8%) with RA, 81/171 (47.4%) with SA, and 26/28 (92.9%) with
      JIA received at least one TNF-alpha antagonist dose during the 1-year follow-up.
      The main physician-reported reason for not starting TNF-alpha antagonists in
      patients with RA or SA was low disease activity (72% for RA and 67% for SA);
      absence of TNF-alpha antagonist therapy was due to patient refusal in only 10%
      and to contraindications in 6% to 7% of cases. CONCLUSIONS: In France, TNF-alpha
      antagonists, which are fully reimbursed by the national health insurance system,
      were used almost routinely in JIA patients unresponsive to methotrexate and were
      given to about half the SA patients with BASDAI>=4 despite NSAID use and a third
      of RA patients with DAS28>3.2 despite methotrexate therapy.

PMID- 26315586
TI  - Comparative responses of river biofilms at the community level to common organic
      solvent and herbicide exposure.
AB  - Residual pesticides applied to crops migrate from agricultural lands to surface
      and ground waters. River biofilms are the first aquatic non-target organisms
      which interact with pesticides. Therefore, ecotoxicological experiments were
      performed at laboratory scale under controlled conditions to investigate the
      community-level responses of river biofilms to a chloroacetanilide herbicide
      (alachlor) and organic solvent (methanol) exposure through the development
      referenced to control. Triplicate rotating annular bioreactors, inoculated with
      river water, were used to cultivate river biofilms under the influence of 1 and
      10 MUg L(-1) of alachlor and 25 mg L(-1) of methanol. For this purpose,
      functional (thymidine incorporation and carbon utilization spectra) and
      structural responses of microbial communities were assessed after 5 weeks of
      development. Structural aspects included biomass (chlorophyll a, confocal laser
      scanning microscopy) and composition (fluor-conjugated lectin binding, molecular
      fingerprinting, and diatom species composition). The addition of alachlor
      resulted in a significant reduction of bacterial biomass at 1 MUg L(-1), whereas
      at 10 MUg L(-1), it induced a significant reduction of exopolymer lectin binding,
      algal, bacterial, and cyanobacterial biomass. However, there were no changes in
      biofilm thickness or thymidine incorporation. No significant difference between
      the bacterial community structures of control and alachlor-treated biofilms was
      revealed by terminal restriction fragment length polymorphism (T-RFLP) analyses.
      However, the methanol-treated bacterial communities appeared different from
      control and alachlor-treated communities. Moreover, methanol treatment resulted
      in an increase of bacterial biomass and thymidine incorporation as well. Changes
      in dominant lectin binding suggested changes in the exopolymeric substances and
      community composition. Chlorophyll a and cyanobacterial biomass were also altered
      by methanol. This study suggested that the concentration-dependent effect of
      alachlor mainly remains limited to biomass and growth inhibition without apparent
      changes of structural and functional characteristics measured. Our work also
      establishes the potential toxic effects of organic solvents on river biofilm in
      ecotoxicological experiments. For the ecotoxicological experiments, the
      alternative of dissolution in organic solvent followed by its evaporation,
      depositing the chemical on a glass surface prior to dissolution in river water
      used here, appears to allow exposure while minimizing the effect of organic
      solvent.

PMID- 26315588
TI  - Potential application of oil-suspended particulate matter aggregates (OSA) on the
      remediation of reflective beaches impacted by petroleum: a mesocosm simulation.
AB  - This paper presents the oil-suspended particulate matter aggregate (OSA) resulted
      from the interaction of droplets of dispersed oil in a water column and
      particulate matter. This structure reduces the adhesion of oil on solid surfaces,
      promotes dispersion, and may accelerate degradation processes. The effects of the
      addition of fine sediments (clay + silt) on the formation of OSA, their impact on
      the dispersion and degradation of the oil, and their potential use in recovering
      reflective sandy beaches were evaluated in a mesoscale simulation model. Two
      simulations were performed (21 days), in the absence and presence of fine
      sediments, with four units in each simulation using oil from the Reconcavo Basin.
      The results showed that the use of fine sediment increased the dispersion of the
      oil in the water column up to four times in relation to the sandy sediment. There
      was no evidence of the transport of hydrocarbons in bottom sediments associated
      with fine sediments that would have accelerated the dispersion and degradation
      rates of the oil. Most of the OSA that formed in this process remained in the
      water column, where the degradation processes were more effective. Over the 21
      days of simulation, we observed a 40 % reduction on average of the levels of
      saturated hydrocarbons staining the surface oil.

PMID- 26315587
TI  - A coordinated set of ecosystem research platforms open to international research
      in ecotoxicology, AnaEE-France.
AB  - The infrastructure for Analysis and Experimentation on Ecosystems (AnaEE-France)
      is an integrated network of the major French experimental, analytical, and
      modeling platforms dedicated to the biological study of continental ecosystems
      (aquatic and terrestrial). This infrastructure aims at understanding and
      predicting ecosystem dynamics under global change. AnaEE-France comprises
      complementary nodes offering access to the best experimental facilities and
      associated biological resources and data: Ecotrons, seminatural experimental
      platforms to manipulate terrestrial and aquatic ecosystems, in natura sites
      equipped for large-scale and long-term experiments. AnaEE-France also provides
      shared instruments and analytical platforms dedicated to environmental (micro)
      biology. Finally, AnaEE-France provides users with data bases and modeling tools
      designed to represent ecosystem dynamics and to go further in coupling
      ecological, agronomical, and evolutionary approaches. In particular, AnaEE-France
      offers adequate services to tackle the new challenges of research in
      ecotoxicology, positioning its various types of platforms in an ecologically
      advanced ecotoxicology approach. AnaEE-France is a leading international
      infrastructure, and it is pioneering the construction of AnaEE (Europe)
      infrastructure in the field of ecosystem research. AnaEE-France infrastructure is
      already open to the international community of scientists in the field of
      continental ecotoxicology.

PMID- 26315589
TI  - Is a Clean Development Mechanism project economically justified? Case study of an
      International Carbon Sequestration Project in Iran.
AB  - The present study evaluates a carbon sequestration project for the three plant
      species in arid and semiarid regions of Iran. Results show that Haloxylon
      performed appropriately in the carbon sequestration process during the 6 years of
      the International Carbon Sequestration Project (ICSP). In addition to a high
      degree of carbon dioxide sequestration, Haloxylon shows high compatibility with
      severe environmental conditions and low maintenance costs. Financial and economic
      analysis demonstrated that the ICSP was justified from an economic perspective.
      The financial assessment showed that net present value (NPV) (US$1,098,022.70),
      internal rate of return (IRR) (21.53%), and payback period (6 years) were in an
      acceptable range. The results of the economic analysis suggested an NPV of
      US$4,407,805.15 and an IRR of 50.63%. Therefore, results of this study suggest
      that there are sufficient incentives for investors to participate in such kind of
      Clean Development Mechanism (CDM) projects.

PMID- 26315590
TI  - Purification of landscape water by using an innovative application of subsurface
      flow constructed wetland.
AB  - This study attempted to purify eutrophic landscape water under a low pollutant
      concentration and high hydraulic volume loading using an embedded subsurface flow
      (SSF) constructed wetland (CW). Three species of aquatic plants (i.e., Cyperus
      alternifolius subsp. flabelliformis, Canna indica, and Hydrocotyle verticillata)
      were found to be conducive to the requirements of purifying the low-polluted
      water. Field results of nearly 2 years of experiments showed that SSF CW purified
      the eutrophic water and maintained the landscape water in a visibly clear
      condition. In an environment approaching the SSF CW background concentration,
      pollutant removal processes were divided into modulation and optimum performance
      periods. Average concentrations of biochemical oxygen demand (BOD), ammonium
      nitrogen (NH4 (+)-N), and total phosphorous (TP) in the optimum performance
      period were 0.69-1.00, 0.35-1.42, and 0.19-0.23 mg/L, respectively. Almost 500
      days of BOD and NH4 (+)-N removals were necessary to perform optimally. A shorter
      period, 350 days, was required for TP optimum removal. This feature of two stage
      removals was not found in chlorophyll-a (Chl-a) and suspended solids (SS), whose
      averages were 11.86-17.98 and 13.30 MUg/L, respectively. Filter cleaning and
      water replacement were unnecessary, while only water recharging was needed to
      compensate for the water lost by evapotranspiration. The field SSF CW has
      maintained its performance level for over 7 years.

PMID- 26315591
TI  - Evaluation of epoxiconazole bioavailability in soil to the earthworm Aporrectodea
      icterica.
AB  - In soil, the determination of total concentration using an exhaustive extraction
      method has little relevance to evaluate the exposure of an organism to a
      chemical, because of sorption processes. This study aims to propose a mild
      extraction method to evaluate the bioavailability of the fungicide epoxiconazole
      to the earthworm Aporrectodea icterica. Experiments were conducted in soils
      presenting various textures and organic carbon contents, spiked with formulated
      epoxiconazole 7 to 56 days prior to their extraction. In parallel, the
      epoxiconazole concentration was determined in exposed earthworms and the
      fungicide's effects were evaluated by measuring weight gain, enzymatic activities
      and total protein contents. Among the various mild chemical solvents tested to
      evaluate the environmental availability of the fungicide, the 50 mM hydroxypropyl
      beta-cyclodextrin solution allowed to extract around 30% of epoxiconazole. This
      percentage corresponded to the ratio determined in exposed A. icterica under
      similar soil conditions. Furthermore, this mild method was demonstrated to be
      sensitive to soil sorption capacities and to ageing. The mild extraction method
      was then applied to explore the relationship between total and (bio)available
      concentrations in soil and in A. icterica, over 7- or 28-day exposure time. This
      demonstrated the proportionality between epoxiconazole concentration in earthworm
      and available in soil (up to 96%, with regression coefficient R(2) = 0.98).
      Sublethal effects on earthworm remained not significant.

PMID- 26315593
TI  - Enhanced coagulation for improving coagulation performance and reducing residual
      aluminum combining polyaluminum chloride with diatomite.
AB  - The feasibility of using enhanced coagulation, which combined polyaluminum
      chloride (PAC) with diatomite for improving coagulation performance and reducing
      the residual aluminum (Al), was discussed. The effects of PAC and diatomite
      dosage on the coagulation performance and residual Al were mainly investigated.
      Results demonstrated that the removal efficiencies of turbidity, dissolved
      organic carbon (DOC), and UV254 were significantly improved by the enhanced
      coagulation, compared with PAC coagulation alone. Meaningfully, the five forms of
      residual Al (total Al (TAl), total dissolved Al (TDAl), dissolved organic Al
      (DOAl), dissolved monomeric Al (DMAl), and dissolved organic monomeric Al
      (DOMAl)) all had different degrees of reduction in the presence of diatomite and
      achieved the lowest concentrations (0.185, 0.06, 0.053, 0.014, and 0 mg L(-1),
      respectively) at a PAC dose of 15 mg L(-1) and diatomite dose of 40 mg L(-1). In
      addition, when PAC was used as coagulant, the majority of residual Al existed in
      dissolved form (about 31.14-70.16%), and the content of DOMAl was small in the
      DMAl.

PMID- 26315594
TI  - Peat and coconut fiber as biofilters for chromium adsorption from contaminated
      wastewaters.
AB  - Batch adsorption experiments were performed for the removal of chromium (III) and
      chromium (VI) ions from aqueous solutions using Canadian peat and coconut fiber.
      The Langmuir model was used to describe the adsorption isotherm. The maximum
      adsorption for peat reached 18.75 mg/g for Cr(III) and 8.02 mg/g for Cr(VI),
      whereas the value for fiber was slightly higher and reached 19.21 mg/g for
      Cr(III) and 9.54 mg/g for Cr(VI). Both chromium forms could be easily eluted from
      the materials. The adsorption of chromium forms to organic matter could be
      explained in terms of formation of donor-acceptor chemical covalent bound with
      hydroxyl groups as ligands and chromium as the central atom in the formed
      complex. The chromate-reducing activities were monitored with the use of electron
      paramagnetic resonance spectroscopy. The results showed that both adsorption and
      reduction occurred simultaneously and the maximum adsorption capacity of
      hexavalent chromium being equal to 95% for fiber and 92% for peat was obtained at
      pH 1.5. The reduction of Cr(VI) in wastewaters began immediately and disappeared
      after 20 h. Both materials contained yeast and fungi species which can be
      responsible for reduction of chromium compounds, due to their enzymatic activity
      (Chwastowski and Koloczek (Acta Biochim Pol 60: 829-834, 2013)). The reduction of
      Cr(VI) is a two-phase process, the first phase being rapid and based on chemical
      reaction and the second phase having biological features. After the recovery
      step, both types of organic materials can be used again for chromium adsorption
      without any loss in the metal uptake. Both of the materials could be used as
      biofilters in the wastewater treatment plants.

PMID- 26315592
TI  - A review on progress of heavy metal removal using adsorbents of microbial and
      plant origin.
AB  - Heavy metals released into the water bodies and on land surfaces by industries
      are highly toxic and carcinogenic in nature. These heavy metals create serious
      threats to all the flora and fauna due to their bioaccumulatory and biomagnifying
      nature at various levels of food chain. Existing conventional technologies for
      heavy metal removal are witnessing a downfall due to high operational cost and
      generation of huge quantity of chemical sludge. Adsorption by various adsorbents
      appears to be a potential alternative of conventional technologies. Its low cost,
      high efficiency, and possibility of adsorbent regeneration for reuse and recovery
      of metal ions for various purposes have allured the scientists to work on this
      technique. The present review compiles the exhaustive information available on
      the utilization of bacteria, algae, fungi, endophytes, aquatic plants, and
      agrowastes as source of adsorbent in adsorption process for removal of heavy
      metals from aquatic medium. During the last few years, a lot of work has been
      conducted on development of adsorbents after modification with various chemical
      and physical techniques. Adsorption of heavy metal ions is a complex process
      affected by operating conditions. As evident from the literature, Langmuir and
      Freundlich are the most widely used isotherm models, while pseudo first and
      second order are popularly studied kinetic models. Further, more researches are
      required in continuous column system and its practical application in wastewater
      treatment.

PMID- 26315595
TI  - Elevated atmospheric CO2 affected photosynthetic products in wheat seedlings and
      biological activity in rhizosphere soil under cadmium stress.
AB  - The objective of this study was to investigate the effects of elevated CO2 (700
      +/- 23 MUmol mol(-1)) on photosynthetic products in wheat seedlings and on
      organic compounds and biological activity in rhizosphere soil under cadmium (Cd)
      stress. Elevated CO2 was associated with decreased quantities of reducing sugars,
      starch, and soluble amino acids, and with increased quantities of soluble sugars,
      total sugars, and soluble proteins in wheat seedlings under Cd stress. The
      contents of total soluble sugars, total free amino acids, total soluble phenolic
      acids, and total organic acids in the rhizosphere soil under Cd stress were
      improved by elevated CO2. Compared to Cd stress alone, the activity of amylase,
      phenol oxidase, urease, L-asparaginase, beta-glucosidase, neutral phosphatase,
      and fluorescein diacetate increased under elevated CO2 in combination with Cd
      stress; only cellulase activity decreased. Bacterial abundance in rhizosphere
      soil was stimulated by elevated CO2 at low Cd concentrations (1.31-5.31 mg Cd kg(
      1) dry soil). Actinomycetes, total microbial abundance, and fungi decreased under
      the combined conditions at 5.31-10.31 mg Cd kg(-1) dry soil. In conclusion,
      increased production of soluble sugars, total sugars, and proteins in wheat
      seedlings under elevated CO2 + Cd stress led to greater quantities of organic
      compounds in the rhizosphere soil relative to seedlings grown under Cd stress
      only. Elevated CO2 concentrations could moderate the effects of heavy metal
      pollution on enzyme activity and microorganism abundance in rhizosphere soils,
      thus improving soil fertility and the microecological rhizosphere environment of
      wheat under Cd stress. 

PMID- 26315596
TI  - Effects of Phosphorylation of beta Subunits of Phycocyanins on State Transition
      in the Model Cyanobacterium Synechocystis sp. PCC 6803.
AB  - Synechocystis sp. PCC 6803 (hereafter Synechocystis) is a model cyanobacterium
      and has been used extensively for studies concerned with photosynthesis and
      environmental adaptation. Although dozens of protein kinases and phosphatases
      with specificity for Ser/Thr/Tyr residues have been predicted, only a few
      substrate proteins are known in Synechocystis. In this study, we report 194 in
      vivo phosphorylation sites from 149 proteins in Synechocystis, which were
      identified using a combination of peptide pre-fractionation, TiO(2) enrichment
      and liquid chromatograpy-tandem mass spectrometry (LC-MS/MS) analysis. These
      phosphorylated proteins are implicated in diverse biological processes, such as
      photosynthesis. Among all identified phosphoproteins involved in photosynthesis,
      the beta subunits of phycocyanins (CpcBs) were found to be phosphorylated on
      Ser22, Ser49, Thr94 and Ser154. Four non-phosphorylated mutants were constructed
      by using site-directed mutagenesis. The in vivo characterization of the cpcB
      mutants showed a slower growth under high light irradiance and displayed
      fluorescence quenching to a lower level and less efficient energy transfer inside
      the phycobilisome (PBS). Notably, the non-phosphorylated mutants exhibited a
      slower state transition than the wild type. The current results demonstrated that
      the phosphorylation status of CpcBs affects the energy transfer and state
      transition of photosynthesis in Synechocystis. This study provides novel insights
      into the molecular mechanisms of protein phosphorylation in the regulation of
      photosynthesis in cyanobacteria and may facilitate the elucidation of the entire
      regulatory network by linking kinases to their physiological substrates.

PMID- 26315598
TI  - Transcriptional mutagenesis by 8-oxodG in alpha-synuclein aggregation and the
      pathogenesis of Parkinson's disease.
AB  - Parkinson's disease (PD) is an age-related progressive neurodegenerative disease
      associated with selective loss of dopaminergic neurons. The characteristic
      hallmark of the disease is intracytoplasmic proteinacious inclusion bodies called
      Lewy bodies, primarily consisting of a presynaptic protein alpha-synuclein.
      Oxidative stress-mediated damage to macromolecules have been shown to occur
      frequently in PD. Oxidative damage to DNA in the form of oxidized guanine (8
      oxodG) accumulates in both the mitochondrial and nuclear DNA of dopaminergic
      neurons of the substantia nigra in PD. 8-oxodG-mediated transcriptional
      mutagenesis has been shown to have the potential to alter phenotype of cells
      through production of mutant pool of proteins. This review comprehensively
      summarizes the role of oxidative stress-mediated damage incurred during
      neurodegeneration, and highlights the scope of transcriptional mutagenesis event
      in leading to alpha-synuclein aggregation as seen in PD. 

PMID- 26315599
TI  - The effect of ferulic acid ethyl ester on leptin-induced proliferation and
      migration of aortic smooth muscle cells.
AB  - Leptin is a peptide hormone, which has a central role in the regulation of body
      weight; it also exerts many potentially atherogenic effects. Ferulic acid ethyl
      ester (FAEE) has been approved for antioxidant properties. The aim of this study
      was to investigate whether FAEE can inhibit the atherogenic effects of leptin and
      the possible molecular mechanism of its action. Both of cell proliferation and
      migration were measured when the aortic smooth muscle cell (A10 cell) treated
      with leptin and/or FAEE. Phosphorylated p44/42MAPK, cell cycle-regulatory protein
      (for example, cyclin D1, p21, p27), beta-catenin and matrix metalloproteinase-9
      (MMP-9) proteins levels were also measured. Results demonstrated that leptin (10,
      100 ng ml(-1)) significantly increased the proliferation of cells and the
      phosphorylation of p44/42MAPK in A10 cells. The proliferative effect of leptin
      was significantly reduced by the pretreatment of U0126 (0.5 MUM), a MEK
      inhibitor, in A10 cells. Meanwhile, leptin significantly increased the protein
      expression of cyclin D1, p21, beta-catenin and decreased the expression of p27 in
      A10 cells. In addition, leptin (10 ng ml(-1)) significantly increased the
      migration of A10 cells and the expression of MMP-9 protein. Above effects of
      leptin were significantly reduced by the pretreatment of FAEE (1 and 10 MUM) in
      A10 cells. In conclusion, FAEE exerts multiple effects on leptin-induced cell
      proliferation and migration, including the inhibition of p44/42MAPK
      phosphorylation, cell cycle-regulatory proteins and MMP-9, thereby suggesting
      that FAEE may be a possible therapeutic approach to the inhibition of obese
      vascular disease. 

PMID- 26315601
TI  - Insulin Resistance May Contribute to Upregulation of Adhesion Molecules on
      Endothelial Cells in Psoriatic Plaques.
AB  - Psoriasis primarily affects the skin, but also has a systemic dimension and is
      associated with severe comorbidities. Since endothelial cells play an important
      role in psoriasis as well as in the development of cardiovascular comorbidities,
      we investigated whether a common mechanism, namely cytokine-induced insulin
      resistance, underlies both pathologies. Activation of the insulin pathway was
      studied in psoriatic skin and dermal endothelial cells. Expression of adhesion
      molecules was assessed by flow cytometry, as well as their biological function in
      flow chamber experiments. The phosphorylation status of Akt, a central kinase in
      the insulin pathway, suggests that endothelial cells within psoriatic plaques are
      rendered insulin resistant by pro-inflammatory cytokines. Insulin counteracts the
      expression of adhesion molecules, but has limited effects on interactions between
      T cells and endothelial cells. Pro-inflammatory cytokines induce insulin
      resistance in endothelial cells, which may contribute to the development of the
      inflammatory infiltrate in psoriasis. 

PMID- 26315600
TI  - Middle East respiratory syndrome coronavirus: transmission, virology and
      therapeutic targeting to aid in outbreak control.
AB  - Middle East respiratory syndrome coronavirus (MERS-CoV) causes high fever, cough,
      acute respiratory tract infection and multiorgan dysfunction that may eventually
      lead to the death of the infected individuals. MERS-CoV is thought to be
      transmitted to humans through dromedary camels. The occurrence of the virus was
      first reported in the Middle East and it subsequently spread to several parts of
      the world. Since 2012, about 1368 infections, including ~487 deaths, have been
      reported worldwide. Notably, the recent human-to-human 'superspreading' of MERS
      CoV in hospitals in South Korea has raised a major global health concern. The
      fatality rate in MERS-CoV infection is four times higher compared with that of
      the closely related severe acute respiratory syndrome coronavirus infection.
      Currently, no drug has been clinically approved to control MERS-CoV infection. In
      this study, we highlight the potential drug targets that can be used to develop
      anti-MERS-CoV therapeutics. 

PMID- 26315602
TI  - Guest Editorial: Special Issue, Anxiety in Children and Adolescents.

PMID- 26315604
TI  - The role of previously untreated patient studies in understanding the development
      of FVIII inhibitors.
AB  - Development of inhibitors against factor VIII (FVIII), the major complication of
      haemophilia A treatment today, is influenced by multiple factors. Genetic (F8
      mutation, family history, ethnicity, polymorphisms in immune modulating genes)
      and non-genetic (intensive exposure to FVIII, presence of pro-inflammatory
      signals as might occur with large bleeds, infections, surgery, or other immune
      stimulants [e.g. vaccines]) risk factors as well as their complex inter
      relationships contribute to the inhibitor risk profile of haemophilia patients,
      particularly in the previously untreated patient (PUP) population. Studies in
      PUPs have been fundamental to furthering the understanding of FVIII inhibitor
      development, as well as discovering previously unappreciated risk factors. The
      multi-factorial nature of inhibitor development makes it difficult to ascertain
      the contribution of FVIII products in inhibitor development through individual
      PUP studies. Sufficiently powered studies of large cohorts may overcome these
      limitations but interpretations should be conducted cautiously. Proper design and
      implementation of PUP safety studies will become even more important with the
      introduction of new molecules, such as extended half-life or human cell-line
      derived FVIII that propose reduced immunogenicity. Despite these difficulties,
      carefully performed clinical studies in PUPs may provide important insights into
      the natural history of the immune response to FVIII and may suggest targets for
      intervention to reduce immunogenicity.

PMID- 26315603
TI  - Increased density of DISC1-immunoreactive oligodendroglial cells in fronto
      parietal white matter of patients with paranoid schizophrenia.
AB  - Profound white matter abnormalities have repeatedly been described in
      schizophrenia, which involve the altered expression of numerous oligodendrocyte
      associated genes. Transcripts of the disrupted-in-schizophrenia 1 (DISC1) gene, a
      key susceptibility factor in schizophrenia, have recently been shown to be
      expressed by oligodendroglial cells and to negatively regulate oligodendrocyte
      differentiation and maturation. To learn more about the putative role(s) of
      oligodendroglia-associated DISC1 in schizophrenia, we analyzed the density of
      DISC1-immunoreactive oligodendrocytes in the fronto-parietal white matter in
      postmortem brains of patients with schizophrenia. Compared with controls (N = 12)
      and cases with undifferentiated/residual schizophrenia (N = 6), there was a
      significantly increased density of DISC1-expressing glial cells in paranoid
      schizophrenia (N = 12), which unlikely resulted from neuroleptic treatment.
      Pathophysiologically, over-expression of DISC1 protein(s) in white matter
      oligodendrocytes might add to the reduced levels of two myelin markers, 2',3'
      cyclic-nucleotide 3'-phosphodiesterase and myelin basic protein in schizophrenia.
      Moreover, it might significantly contribute to cell cycle abnormalities as well
      as to deficits in oligodendroglial cell differentiation and maturation found in
      schizophrenia. 

PMID- 26315605
TI  - Characterization of a solvent, surfactant and temperature-tolerant laccase from
      Pleurotus sp. MAK-II and its dye decolorizing property.
AB  - OBJECTIVE: Laccase is industrially important but a major challenge is the
      production of an ideal laccase with suitable physicochemical properties to
      tolerate temperature, surfactants, metal ions and solvents towards its potential
      application in bioremediation. RESULTS: A laccase with a molecular mass of 43 kDa
      was purified from Pleurotus sp. MAK-II. It was optimally active at pH 4.5 and 60 
      degrees C using ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) as
      substrate. The laccase was susceptible to NaN3 and NaCN. Activity was strongly
      enhanced by Cu(2+), Mg(2+) and Ca(2+). The purified laccase showed stability
      towards various surfactants and solvents and decolorized, in the presence of
      violuric acid as redox mediator, the diazo dye Congo Red and the anthraquinone
      dye Remazol Brilliant Blue R to the extent of 96 and 72 %, respectively.
      CONCLUSION: The ideal physicochemical properties of Pleurotus sp. MAK-II-derived
      laccase suggest that it could be effectively used in the textile dye industry.

PMID- 26315606
TI  - Exogenous transglutaminase improves multiple-stress tolerance in Lactococcus
      lactis and other lactic acid bacteria with glutamine and lysine in the cell wall.
AB  - OBJECTIVE: To increase the resistance of ingested bacteria to multiple
      environmental stresses, the role of transglutaminase in Lactococcus lactis and
      possible mechanisms of action were explored. RESULTS: L. lactis grown with
      transglutaminase exhibited significantly higher resistance to bile salts,
      stimulated gastric juice, antibiotics, NaCl, and cold stress compared to the
      control (cultured without transglutaminase), with no negative influence on cell
      growth. Transmission electron microscopy revealed that the cell walls of L.
      lactis cultured with 9 U transglutaminase/ml were approx. 1.9-times thicker than
      the control. Further analysis demonstrated that the multi-resistant phenotype was
      strain-specific; that is, it occurred in bacteria with the presence of glutamine
      and lysine in the peptidoglycan. CONCLUSION: Supplementation of culture media
      with transglutaminase is an effective, simple, and inexpensive strategy to
      protect specific ingested bacteria against multiple environmental challenges.

PMID- 26315607
TI  - CDK14 Contributes to Reactive Gliosis via Interaction with Cyclin Y in Rat Model
      of Spinal Cord Injury.
AB  - Cyclin-dependent kinases (CDKs) are perceived as the engine that drives cell
      cycle progression whereas cyclins are considered to be the gears that are changed
      to aid the transition between cycle phases. CDK14 is a cdc2-related
      serine/threonine protein kinase and plays an important role in normal cell cycle
      progression. However, its distribution and function in the central nervous system
      (CNS) lesion remain unclear. In this study, we mainly investigated the protein
      expression and cellular localization of CDK14 during spinal cord injury (SCI).
      Western blot analysis revealed that the expression of CDK14 was gradually
      increased and reached a peak at 3 days after SCI. The expression of CDK14 was
      further analyzed by immunohistochemistry. Double immunofluorescence staining
      showed that CDK14 was co-expressed prominent in astrocytes. Co-localization
      CDK14/proliferating cell nuclear antigen (PCNA) were detected in glial cells.
      cyclin Y, which can interact with CDK14, was detected that had same expression
      trend was consistent with CDK14 Western blot results in SCI. Double
      immunofluorescence staining indicated that CDK14 co-expressed with cyclin Y in
      some cells. Co-immunoprecipitation had been showed that CDK14 could interact with
      cyclin Y after acute SCI. Taken together, these data suggested that both CDK14
      and cyclin Y may play important roles in spinal cord pathophysiology.

PMID- 26315608
TI  - ADNP/ADNP2 expression in oligodendrocytes: implication for myelin-related
      neurodevelopment.
AB  - Oligodendrocytes, the myelin-forming cells of the central nervous system, play
      important roles in brain development and maintenance. Activity-dependent
      neuroprotective protein (ADNP), an early marker essential for brain formation,
      interacts with microtubule end-binding proteins (EB1, EB2, and EB3). EB1 and EB3
      are highly expressed in neurons (axons and dendritic spines, respectively) and
      EB1 enhancement of neurite outgrowth is attenuated by EB2. ADNP/EB presence in
      oligodendrocytes has not been studied so far. Here, we measured messenger RNA
      (mRNA) levels of ADNP and EB1-EB3 in rat brain oligodendrocytes during culture
      maturation and in rat brains during development (1, 35, and 75 days) in
      comparison with rat astrocytes, dorsal root ganglion (DRG) neurons, and the
      oligodendroglia cell lines (OLN-93 cell line, not expressing the microtubule
      associated protein (MAP) tau, and OLN-93 cells stably transfected to express
      various forms of tau). Results showed that all transcripts studied were expressed
      in oligodendrocytes. ADNP and EB2 mRNA transcript content peaked at the time of
      oligodendrocyte maturation (5 days in vitro) and was highest in newborn rat
      brains compared with mature brains. ADNP2 (the only family member of ADNP), and
      EB1, although expressed in lower quantities, essentially paralleled ADNP and EB2
      expression patterns, respectively. EB3 mRNA, peaking upon oligodendrocyte
      maturation, showed an apparent second peak of expression (10 days in vitro) and
      increased in the mature rat brain compared with the newborn brain. DRG cells
      expressed the highest levels of EB3, when compared with oligodendrocyte
      precursors and with astrocytes but not when compared with mature
      oligodendrocytes. Mature oligodendrocytes and oligodendrocyte precursors
      expressed ~30-40-fold more EB2 vs. EB3, and ~4-7-fold vs. ADNP. DRGs expressed ~5
      fold more EB2 vs. EB3 and astrocytes showed an in-between (~20-fold) ratio. Only
      DRGs expressed similar EB1 and EB3 transcript levels, contrasting with
      oligodendrocyte and astrocytes (~10-30-fold more EB1). Astrocytes expressed more
      ADNP than DRGs and oligodendrocyte precursor cells (~2-fold) but not compared
      with mature oligodendrocytes. EB1 and EB3 were previously found to be associated
      with tau. Immortalized oligodendrocytes showed an intermediate phenotype of mRNA
      expression compared with oligodendrocyte precursor cells and mature
      oligodendrocytes with tau transfection reducing overall ADNP and EB expression.
      In summary, ADNPs and EBs are highly expressed in oligodendrocytes suggesting an
      impact on myelin formation in health and disease. 

PMID- 26315609
TI  - Evaluation of Su Fu'ning Lotion's Inhibitory Effects on Bladder Cancer Cells In
      Vitro and In Vivo by Intravesical Instillation.
AB  - BACKGROUND: Bladder cancer is a common malignant tumor with a very high
      recurrence rate after surgery. Intravesical instillation can help clear up the
      residual tumor cells after surgery and thereby reduce the recurrence rate.
      OBJECTIVE: To establish a bladder tumor transplantation animal model and to
      evaluate the inhibitory effects of a novel perfusate, Su Fu'ning Lotion (SFN), on
      bladder tumor. METHODS: SFN was compared with several commonly used chemotherapy
      drugs, including mitomycin (MMC) and pirarubicin (THP) for anticancer effects on
      the bladder cancer cell lines T24, BTT, and BIU-87 and SFN half inhibitory
      concentrations (IC50) were determined after 48 hours of treatment. In addition,
      bladder cancer orthotopic transplantation tumor models were established in BALB/C
      nude mice and T739 mice, and SFN anticancer effects were assessed in vivo, with
      normal saline and MMC as negative and positive controls, respectively. RESULTS:
      SFN, MMC, and THP were all lethal to bladder cancer cells, in vitro, with SFN and
      THP significantly superior to MMC. IC50 values for SFN were 13.22, 11.22, and
      12.5 ug/mL on T24, BTT, and BIU-87 cells, respectively. In vivo, SFN
      significantly reduced the mouse bladder wet weight and prolonged the animal
      survival compared with controls (P < .05), suggesting that SFN significantly
      inhibited T24/BTT cell growth in mice. CONCLUSION: SFN inhibited the bladder
      cancer cell proliferation in vitro and in vivo and significantly prolonged the
      survival of mice with bladder cancer xenografts, indicating that SFN could be
      used as a perfusate after surgery for removal of residual bladder cancers cells.

PMID- 26315610
TI  - Protein corona mitigates the cytotoxicity of graphene oxide by reducing its
      physical interaction with cell membrane.
AB  - Many recent studies have shown that the way nanoparticles interact with cells and
      biological molecules can vary greatly in the serum-containing or serum-free
      culture medium. However, the underlying molecular mechanisms of how the so-called
      "protein corona" formed in serum medium affects nanoparticles' biological
      responses are still largely unresolved. Thus, it is critical to understand how
      absorbed proteins on the surfaces of nanoparticles alter their biological
      effects. In this work, we have demonstrated with both experimental and
      theoretical approaches that protein BSA coating can mitigate the cytotoxicity of
      graphene oxide (GO) by reducing its cell membrane penetration. Our cell viability
      and cellular uptake experiments showed that protein corona decreased cellular
      uptake of GO, thus significantly mitigating the potential cytotoxicity of GO. The
      electron microscopy images also confirmed that protein corona reduced the
      cellular morphological damage by limiting GO penetration into the cell membrane.
      Further molecular dynamics (MD) simulations validated the experimental results
      and revealed that the adsorbed BSA in effect weakened the interaction between the
      phospholipids and graphene surface due to a reduction of the available surface
      area plus an unfavorable steric effect, thus significantly reducing the graphene
      penetration and lipid bilayer damaging. These findings provide new insights into
      the underlying molecular mechanism of this important graphene protein corona
      interaction with cell membranes, and should have implications in future
      development of graphene-based biomedical applications. 

PMID- 26315611
TI  - Evolution of Patient Decision-Making Regarding Medical Treatment of Rheumatoid
      Arthritis.
AB  - OBJECTIVE: The migration of health care toward a consumer-driven system favors
      increased patient participation during the treatment decision-making process.
      Patient involvement in treatment decision discussions has been linked to
      increased treatment adherence and patient satisfaction. Previous studies have
      quantified decision-making styles of patients with rheumatoid arthritis (RA);
      however, none of them have considered the evolution of patient involvement after
      living with RA for many years. We conducted a qualitative study to determine the
      decision-making model used by long-term RA patients, and to describe the changes
      in their involvement over time. METHODS: Twenty participants were recruited from
      the ongoing Silicone Arthroplasty in Rheumatoid Arthritis study. Semistructured
      interviews were conducted and data were analyzed using grounded theory
      methodology. RESULTS: Nineteen out of 20 participants recalled using the
      paternalistic decision-making (PDM) model immediately following their diagnosis.
      Fourteen of the 19 participants who initially used PDM evolved to shared decision
      making (SDM). Participants attributed the change in involvement to the
      development of a trusting relationship with their physician, as well as to
      becoming educated about the disease. CONCLUSION: When initially diagnosed with
      RA, patients may let their physician decide on the best treatment course.
      However, over time patients may evolve to exercise a more collaborative role.
      Physicians should understand that even within SDM, each patient can demonstrate a
      varied amount of autonomy. It is up to the physician to have a discussion with
      each patient to determine his or her desired level of involvement.

PMID- 26315612
TI  - Quantitative and qualitative determination of LiuweiDihuang preparations by ultra
      high performance liquid chromatography in dual-wavelength fingerprinting mode and
      random forest.
AB  - The classical traditional Chinese formulation LiuweiDihuang, shown to have
      clinical efficacy for "nourishing kidney-yin" in traditional Chinese medicine,
      has been used for thousands of years in China. Little attention, however, has
      been paid to quality control methods for this formulation. Hence, a rapid and
      sensitive analytical technique is urgently needed for the evaluation of
      LiuweiDihuang preparations to assess its quality and pharmacological
      functionality. In this study, an ultra high performance liquid chromatography
      dual-wavelength method was developed to simultaneously determine 11 constituents
      in LiuweiDihuang preparations. This robust approach provided a fast and
      comprehensive quantitative determination of the major bioactive markers within
      LiuweiDihuang preparations. To distinguish four dosage forms of LiuweiDihuang
      preparations, a random forest technique was applied on the spectrometric
      fingerprint data obtained. This combination approach of chromatographic
      techniques and data analyses might serve as a rapid and efficient tool to ensure
      the quality of LiuweiDihuang preparations and other Chinese medicinal
      formulations and can support quality control and scientific research into the
      pharmacological potential for these formulations. 

PMID- 26315613
TI  - Re-examining tau-immunoreactive pathology in the population: granulovacuolar
      degeneration and neurofibrillary tangles.
AB  - INTRODUCTION: Alzheimer's disease (AD) is associated with neurofibrillary
      pathology, including neurofibrillary tangles (NFT), neuritic plaques (NP) and
      neuropil threads containing aggregated microtubule associated protein tau.
      Aggregated tau is also associated with granulovacuolar degeneration (GVD). The
      relationships between tau, GVD, NFT and dementia are unclear. METHODS: We
      assessed hippocampal (CA1) tau-immunoreactive GVD and NFT pathology in brain
      donations from the population-representative Cambridge City over 75s Cohort
      (CC75C) using the CERAD protocol and a modified protocol that included a
      morphological characterisation of tau-immunoreactive deposits within neurons as
      NFTs or as GVD. Associations between GVD, NFT and dementia were investigated.
      RESULTS: Hippocampal pyramidal neurons affected with either NFT or GVD are common
      in the older population. Some tau-immunoreactive deposits resemble ghost GVD
      neurons. Tau immunoreactivity identified GVD in 95% cases rated as none with
      haematoxylin and eosin staining. Both severe NFT (odds ratio (OR) 7.33, 95%
      confidence interval (CI) 2.01; 26.80, p = 0.003) and severe GVD (OR 7.48, 95%
      (CI) 1.54; 36.24, p = 0.012) were associated with dementia status. Increasing NFT
      (OR 2.47 95% (CI) 1.45; 4.22, p = 0.001) and GVD (OR 2.12 95% (CI) 1.23; 3.64, p
      = 0.007) severities are associated with increasing dementia severity. However,
      when the analyses were controlled for other neuropathologies (NFT, NP, Tar-DNA
      binding Protein-43 and amyloid deposits), the associations between GVD and
      dementia lost significance. CONCLUSIONS: Current neuropathological assessments do
      not adequately evaluate the presence and severity of the GVD pathology and its
      contribution to dementia remains unclear. We recommend that protocols to assess
      GVD should be developed for routine use and that tau, in a non-PHF associated
      conformation, is reliably associated with GVD.

PMID- 26315614
TI  - Therapeutic Developments for Tics and Myoclonus.
AB  - Tics and myoclonus are phenomenologically similar given that both are jerk-like
      movements, but, in contrast to myoclonus, tics are often preceded by premonitory
      sensations and are typically associated with a variety of behavioral
      comorbidities, including attention deficit and obsessive-compulsive disorder.
      There are many other clinical features that help differentiate these two
      hyperkinetic disorders. Whereas behavioral and antidopaminergic therapies are
      most effective in the management of tics, clonazepam, other anticonvulsants, and
      serotonergic drugs are often used to control myoclonic movements. Botulinum toxin
      may also be helpful in focal tics and in segmental forms of myoclonus. DBS plays
      an increasingly important role in the treatment of these disorders, particularly
      when they are generalized and are disabling despite optimal medical therapy.

PMID- 26315615
TI  - Expansion of Thiele's Acid Chemistry in Pursuit of a Suite of Conformationally
      Constrained Scaffolds.
AB  - The Diels-Alder dimer of cyclopentadiene carboxylate, Thiele's acid has
      conformational properties that make it attractive as a molecular scaffold for
      applications in supramolecular and biological chemistry. However, a lack of known
      reaction methodology for derivatives of Thiele's acid (or the corresponding
      esters) has hampered its utilization in these fields. We describe an improved
      preparation of Thiele's esters and survey the chemistry of these versatile
      intermediates. As part of this effort, we also describe the synthesis of a suite
      of Thiele's acid (or ester) analogues spanning a broad range of cleft angles. 

PMID- 26315617
TI  - Breast and Prostate Cancer Survivor Responses to Group Exercise and Supportive
      Group Psychotherapy.
AB  - This study qualitatively examined an 8-week group exercise and counseling
      intervention for breast and prostate cancer survivors. Groups exercised 3 days
      per week, 50 minutes per session, performing moderate-intensity aerobic and
      resistance training. Groups also underwent 90-minute supportive group
      psychotherapy sessions once per week. Survivors discussed their experiences in
      focus groups post intervention. Transcripts were analyzed using interpretative
      phenomenological analysis. Survivors described how exercise facilitated
      counseling by creating mutual aid and trust, and counseling helped participants
      with self-identity, sexuality, and the return to normalcy. When possible,
      counselors and fitness professionals should create partnerships to optimally
      support cancer survivors.

PMID- 26315618
TI  - Uterine leiomyosarcoma with osteoclast-like giant cells associated with high
      expression of receptor activator of nuclear factor kappaB ligand.
AB  - The occurrence of osteoclast-like giant cells (OLGCs) in uterine leiomyosarcomas
      (LMSs) is a rare phenomenon. The nature of OLGCs and the significance of their
      accumulation in these tumors are poorly understood. Recent studies revealed that
      the formation of osteoclasts requires a specific cytokine, receptor activator of
      nuclear factor kappaB ligand (RANKL), in bone. In this study, we investigated the
      expression of RANKL in 2 cases of uterine LMS with OLGCs by means of
      immunohistochemistry and compared the extent of RANKL expression with that in
      conventional uterine LMSs and leiomyomas by using real-time reverse-transcription
      quantitative polymerase chain reaction. Our cases of uterine LMS with OLGCs
      showed markedly high expression of RANKL messenger RNA with clear RANKL
      immunoreactivity compared with messenger RNA expression and immunoreactivity of
      conventional uterine LMSs and leiomyomas. These findings suggest that the tumors
      producing RANKL may account for accumulation of OLGCs in tumor tissue because of
      RANKL-related osteoclastogenesis. 

PMID- 26315616
TI  - Targeting CDK6 in cancer: State of the art and new insights.
AB  - Cyclin-dependent kinase 6 (CDK6) plays a vital role in regulating the progression
      of the cell cycle. More recently, CDK6 has also been shown to have a
      transcriptional role in tumor angiogenesis. Up-regulated CDK6 activity is
      associated with the development of several types of cancers. While CDK6 is over
      expressed in cancer cells, it has a low detectable level in non-cancerous cells
      and CDK6-null mice develop normally, suggesting a specific oncogenic role of
      CDK6, and that its inhibition may represent an ideal mechanism-based and low
      toxic therapeutic strategy in cancer treatment. Identification of selective small
      molecule inhibitors of CDK6 is thus needed for drug development. Herein, we
      review the latest understandings of the biological regulation and oncogenic roles
      of CDK6. The potential clinical relevance of CDK6 inhibition, the progress in the
      development of small-molecule CDK6 inhibitors and the rational design of
      potential selective CDK6 inhibitors are also discussed. 

PMID- 26315619
TI  - Bifunctional Manganese Ferrite/Polyaniline Hybrid as Electrode Material for
      Enhanced Energy Recovery in Microbial Fuel Cell.
AB  - Microbial fuel cells (MFCs) are emerging as a sustainable technology for waste to
      energy conversion where electrode materials play a vital role on its performance.
      Platinum (Pt) is the most common material used as cathode catalyst in the MFCs.
      However, the high cost and low earth abundance associated with Pt prompt the
      researcher to explore inexpensive catalysts. The present study demonstrates a
      noble metal-free MFC using a manganese ferrite (MnFe2O4)/polyaniline (PANI)-based
      electrode material. The MnFe2O4 nanoparticles (NPs) and MnFe2O4 NPs/PANI hybrid
      composite not only exhibited superior oxygen reduction reaction (ORR) activity
      for the air cathode but also enhanced anode half-cell potential upon modifying
      carbon cloth anode in the single-chambered MFC. This is attributed to the
      improved extracellular electron transfer of exoelectrogens due to Fe(3+) in
      MnFe2O4 and its capacitive nature. The present work demonstrates for the first
      time the dual property of MnFe2O4 NPs/PANI, i.e., as cathode catalyst and an
      anode modifier, thereby promising cost-effective MFCs for practical applications.

PMID- 26315620
TI  - Neutrophil-lymphocyte ratio: Can clinicians really trust it as an inflammatory
      indicator?

PMID- 26315621
TI  - Response to the Letter to the Editor: "Neutrophil-lymphocyte ratio: Can
      clinicians really trust it as an inflammatory indicator?".

PMID- 26315622
TI  - Iron metabolism and incidence of metabolic syndrome.
AB  - BACKGROUND AND AIMS: Whether iron metabolism affects metabolic syndrome (METS) is
      debated. We assessed the association between several markers of iron metabolism
      and incidence of METS. METHODS AND RESULTS: Data from 3271 participants (1870
      women, 51.3 +/- 10.4 years), free of METS at baseline and followed for 5.5 years.
      The association of serum iron, ferritin and transferrin with incident METS was
      assessed separately by gender. Incidence of METS was 22.6% in men and 16.5% in
      women (p < 0.001). After multivariate adjustment, a positive association was
      found between transferrin and incident METS in men: odds ratio (OR) and 95%
      confidence interval for the fourth relative to the first quartile 1.55 (1.04
      2.31), p for trend = 0.03, while no association was found for iron OR = 0.81
      (0.53-1.24), p for trend = 0.33 and ferritin OR = 1.30 (0.88-1.92), p for trend =
      0.018. In women, a negative association was found between iron and incident METS:
      OR for the fourth relative to the first quartile 0.51 (0.33-0.80), p for
      trend<0.03; the association between transferrin and incident METS was borderline
      significant: OR = 1.45 (0.97-2.17), p for trend = 0.07 and no association was
      found for ferritin: OR = 1.11 (0.76-1.63), p for trend = 0.58. CONCLUSION:
      Transferrin, not ferritin, is independently associated with an increased risk of
      incident METS; the protective effect of iron in women should be further explored.

PMID- 26315623
TI  - Overnourishment during lactation induces metabolic and haemodynamic heart
      impairment during adulthood.
AB  - AIM: In this study, the effects of postnatal overfeeding on heart energy
      homoeostasis and cardiac haemodynamics in adult male Swiss mice were examined.
      METHODS AND RESULTS: During the suckling period, the mice were divided into four
      groups of control or overfed pups in combination with baseline or
      ischaemia/reperfusion treatments (control group baseline, CGBL; overfed group
      baseline, OGBL; control group ischaemia/reperfusion, CGIR; and overfed group
      ischaemia/reperfusion, OGIR). End diastolic pressure (EDP), heart contraction
      speed (Max dP/dt), relaxation speed (Min dP/dt), isovolumetric relaxation time
      (Tau) and frequency by beats per minute (BPM) were measured. During baseline and
      ischaemia/reperfusion, key proteins such as AKT1, AKT2, AKT3, pAKT, adenosine
      monophosphate-activated protein kinase (AMPK), pAMPK, insulin receptor beta
      (IRbeta), protein tyrosine phosphatase 1B (PTP1B), insulin receptor substrate 1
      (IRS1), fatty acid binding protein (FABP), CD36, phosphoinositide 3-kinase (PI3K)
      and peroxisome proliferator-activated receptor gamma coactivator 1-alpha
      (PGC1alpha) were studied. The expression of atrial natriuretic peptide (ANP), B
      type natriuretic peptide (BNP), carnitine palmitoyltransferase 1 (CPT1) and
      uncoupling protein 3 (UCP3) was studied as a marker of cardiac hypertrophy and
      energetic metabolism. Cardiac fibrosis was analyzed by quantifying collagen
      deposition, which is increased in the OGBL and OGIR groups compared with the
      control groups. CONCLUSIONS: The OGBL group showed reduced EDP compared with the
      CGBL group and high Max dP/dt compared with the OGBL group. Ischaemia/reperfusion
      increased EDP and Min dP/dt in the intragroup comparison. By contrast, Tau and
      frequency were not significantly different among groups. The OGIR mice showed
      significant alterations in heart metabolism proteins, including AKT2, pAKT/AKT1,
      pAKT/AKT2, AMPK, pAMPK/AMPK, PTP1B, IRS1, FABP and CD36. Furthermore, alterations
      in ANP, BNP, CPT1 and UCP3 messenger RNA (mRNA) expression indicated hypertrophy
      and reduction in their efficiency, such that exclusive overnutrition in childhood
      induces a long-term effect on haemodynamics, metabolism and heart remodelling.

PMID- 26315625
TI  - Education level and chronic liver disease by aetiology: A proportional mortality
      study.
AB  - BACKGROUND: Data are lacking on mortality from chronic liver diseases of
      different aetiology by education level. AIMS: To investigate the association
      between education level and mortality from alcoholic, viral, and non-viral/non
      alcoholic chronic liver disease. METHODS: Proportional mortality was investigated
      in 2011-2013 in the Veneto Region (Italy). Odds ratios were estimated by
      conditional logistic regression with deaths from liver cirrhosis, liver cancer,
      and viral hepatitis as cases, and all other deaths as controls. Disease aetiology
      was determined from all conditions mentioned in the death certificate. RESULTS:
      Overall chronic liver disease proportional mortality was higher in males (OR
      1.37, 95% CI 1.18-1.60) and females (OR 1.72, 95% CI 1.29-2.30) with primary
      education than in subjects with higher educational level. The risk for alcohol
      related and non-viral/non-alcohol-related disease significantly increased with
      lower education in both genders. CONCLUSIONS: Proportional mortality analysis of
      multiple causes of death records showed an association between education and
      chronic liver diseases with alcoholic and non-viral/non-alcoholic aetiology.

PMID- 26315624
TI  - Genome sequencing of herb Tulsi (Ocimum tenuiflorum) unravels key genes behind
      its strong medicinal properties.
AB  - BACKGROUND: Krishna Tulsi, a member of Lamiaceae family, is a herb well known for
      its spiritual, religious and medicinal importance in India. The common name of
      this plant is 'Tulsi' (or 'Tulasi' or 'Thulasi') and is considered sacred by
      Hindus. We present the draft genome of Ocimum tenuiflurum L (subtype Krishna
      Tulsi) in this report. The paired-end and mate-pair sequence libraries were
      generated for the whole genome sequenced with the Illumina Hiseq 1000, resulting
      in an assembled genome of 374 Mb, with a genome coverage of 61 % (612 Mb
      estimated genome size). We have also studied transcriptomes (RNA-Seq) of two
      subtypes of O. tenuiflorum, Krishna and Rama Tulsi and report the relative
      expression of genes in both the varieties. RESULTS: The pathways leading to the
      production of medicinally-important specialized metabolites have been studied in
      detail, in relation to similar pathways in Arabidopsis thaliana and other plants.
      Expression levels of anthocyanin biosynthesis-related genes in leaf samples of
      Krishna Tulsi were observed to be relatively high, explaining the purple
      colouration of Krishna Tulsi leaves. The expression of six important genes
      identified from genome data were validated by performing q-RT-PCR in different
      tissues of five different species, which shows the high extent of urosolic acid
      producing genes in young leaves of the Rama subtype. In addition, the presence of
      eugenol and ursolic acid, implied as potential drugs in the cure of many diseases
      including cancer was confirmed using mass spectrometry. CONCLUSIONS: The
      availability of the whole genome of O.tenuiflorum and our sequence analysis
      suggests that small amino acid changes at the functional sites of genes involved
      in metabolite synthesis pathways confer special medicinal properties to this
      herb.

PMID- 26315626
TI  - Differential Sequestration of a Cytotoxic Vismione from the Host Plant Vismia
      baccifera by Periphoba arcaei and Pyrrhopyge thericles.
AB  - We sought to compare the abilities of the specialist Lepidoptera Pyrrhopyge
      thericles (Hesperiidae) and the generalist Periphoba arcaei (Saturniidae) to
      assimilate three highly cytotoxic compounds from their larval host plant, Vismia
      baccifera (Clusiaceae) and to determine whether either insect discriminated in
      its assimilation of the compounds that are structurally similar but of variable
      cytotoxicity. Vismione B (1), deacetylvismione A (2), and deacetylvismione H (3)
      are cytotoxic compounds isolated from V. baccifera. Compound 1 was found in the
      2nd and 3rd instars of P. arcaei, but not in the mature larvae or the pupae.
      Pyrrhopyge thericles assimilated trace quantities of compound 1 and
      deacetylvismione A (2), which were both found in the 3rd and 4th instars. In
      extracts of V. baccifera, compound 2 is present at levels approximately 6-fold
      greater than compound 1, indicating that the generalist P. arcaei is capable of
      selectively sequestering cytotoxic compounds from its host plant. Compounds 1 and
      2 show comparable cytotoxicities in three different cancer cell lines, suggesting
      that properties other than cytotoxicity are responsible for the selective
      sequestration of 1 by P. arcaei. This study represents the first time that
      sequestration of this class of compounds has been recorded in the Lepidoptera. 

PMID- 26315627
TI  - North American Invasion of the Tawny Crazy Ant (Nylanderia fulva) Is Enabled by
      Pheromonal Synergism from Two Separate Glands.
AB  - A new invader, the "tawny crazy ant", Nylanderia fulva (Hymenoptera: Formicidae;
      Formicinae), is displacing the red imported fire ant, Solenopsis invicta
      (Formicidae: Myrmicinae), in the southern U.S., likely through its superior
      chemical arsenal and communication. Alone, formic acid is unattractive, but this
      venom (= poison) acid powerfully synergizes attraction of tawny crazy ants to
      volatiles from the Dufour's gland secretion of N. fulva workers, including the
      two major components, undecane and 2-tridecanone. The unexpected pheromonal
      synergism between the Dufour's gland and the venom gland appears to be another
      key factor, in addition to previously known defensive and detoxification
      semiochemical features, for the successful invasion and domination of N. fulva in
      the southern U.S. This synergism is an efficient mechanism enabling N. fulva
      workers to outcompete Solenopsis and other ant species for food and territory.
      From a practical standpoint, judicious point-source release formulation of tawny
      crazy ant volatiles may be pivotal for enhanced attract-and-kill management of
      this pest. 

PMID- 26315628
TI  - The History of Geriatric Anesthesia in the United States and the Society for the
      Advancement of Geriatric Anesthesia.
AB  - Creation of the American Society of Anesthesiologists Committee on Geriatric
      Anesthesia provided an opportunity for individuals to interact, strategize, and
      work with medical organizations outside of anesthesiology. These opportunities
      expanded with creation of the Society for the Advancement of Geriatric
      Anesthesia. The American Geriatrics Society provided a major boost when they
      realized it was important for surgical and related specialties to take an active
      role in the care of older patients. From this have come educational grants to
      improve residency training and establishment of a major research grant program
      now managed by the National Institutes of Health. Nevertheless, for improved care
      of the older patient, the level of involvement has to increase. 

PMID- 26315629
TI  - Geriatrics and the Perioperative Surgical Home.
AB  - An ever-changing health care system with a constantly increasing aging surgical
      population creates both opportunities for providing improved health care as well
      as significant challenges. Coordinated health care initiatives are needed if one
      is to adequately balance the need for evidence-based improved patient outcomes
      and the often-associated increased costs. In this article the authors postulate
      that a protocol-driven, multidisciplinary approach may be a pathway for
      implementing an effective triple aim to health care, especially in a frail
      geriatric population. 

PMID- 26315630
TI  - Physiology Considerations in Geriatric Patients.
AB  - Physiology changes at the structural, functional, and molecular levels as people
      age, and every major organ system experiences physiologic change with time. The
      changes to the nervous system result mostly in cognitive impairments, the
      cardiovascular system develops higher blood pressures with lower cardiac output,
      the respiratory system undergoes a reduction of arterial oxyhemoglobin levels,
      the gastrointestinal system experiences delayed gastric emptying and reduction of
      hepatic metabolism, and the renal system experiences a diminished glomerular
      filtration rate. Combined, these changes create a complex physiologic condition.
      This unique physiology must be taken into consideration for geriatric patients
      undergoing general anesthesia. 

PMID- 26315631
TI  - Geriatric Pharmacology.
AB  - Aging involves changes in several physiologic processes that lead to decreased
      volumes of distribution, slowed metabolism, and increased end-organ sensitivity
      to anesthetics. These changes generally result in increased potency. Elderly
      patients require less anesthetic medication, but the true extent of reduction is
      underappreciated and less uniformly practiced. The impact of potential anesthetic
      drug overdosing on intermediate and long-term outcomes is not fully appreciated.
      It may be necessary to consider age as a continuous variable for anesthetic drug
      dosing in older patients rather than treating adult versus elderly patients.
      Further pharmacologic studies are required in people more than 85 years old. 

PMID- 26315632
TI  - Preoperative Assessment of Geriatric Patients.
AB  - The preoperative assessment of geriatric patients provides an excellent
      opportunity to evaluate the patient for perioperative risk factors such as
      frailty, functional status, nutritional status, cardiovascular and pulmonary
      status, and substance dependence. It also provides an overall clinical picture on
      which health care providers can base a framework to reduce these risk factors. 

PMID- 26315633
TI  - Optimal Preoperative Evaluation and Perioperative Care of the Geriatric Patient:
      A Surgeon's Perspective.
AB  - The elderly preoperative patient benefits from an assessment that includes more
      than a routine physical examination and electrocardiogram. Such an assessment
      includes domains likely to affect the elderly: cognition, functionality, frailty,
      polypharmacy, nutrition, and social support. This fosters decisions based on
      functional age rather than chronologic age and on each patient as an individual.
      One such assessment is that promulgated by the American College of Surgeons
      National Surgery Quality Improvement Program/American Geriatrics Society Best
      Practice Guidelines. We should not miss any opportunity to improve results in
      this growing population of surgical patients. 

PMID- 26315634
TI  - Anesthetic Considerations for Common Procedures in Geriatric Patients: Hip
      Fracture, Emergency General Surgery, and Transcatheter Aortic Valve Replacement.
AB  - The elderly population is growing. Geriatric patients undergo a large proportion
      of surgical procedures and have increased complications, morbidity, and
      mortality, which may be associated with increased intensive care unit time,
      length of stay, hospital readmission, and cost. Identification of optimal
      anesthetic care for these patients, leading to decreased complications and
      contributing to best possible outcomes, will have great value. This article
      reviews the anesthetic considerations for intraoperative care of geriatric
      patients and focus on 3 procedures (hip fractures, emergency abdominal surgery,
      and transcatheter aortic valve replacement). An approach to evaluation and
      management of the elderly surgical patient is described. 

PMID- 26315635
TI  - Postoperative Delirium in the Geriatric Patient.
AB  - Postoperative delirium, a common complication in older surgical patients, is
      independently associated with increased morbidity and mortality. Patients older
      than 65 years receive greater than one-third of the more than 40 million
      anesthetics delivered yearly in the United States. This number is expected to
      increase with the aging of the population. Thus, it is increasingly important
      that perioperative clinicians who care for geriatric patients have an
      understanding of the complex syndrome of postoperative delirium. 

PMID- 26315637
TI  - Critical Care Issues of the Geriatric Patient.
AB  - Medical care of the geriatric patient is an important area of focus as the
      population ages and life expectancy increases. In particular, critical care of
      the geriatric patient will be especially affected, because geriatric patients
      will consume most critical care beds in the future and subsequently require
      increased use of resources. This review focuses on the physiologic effects of
      aging on all body systems. Focus on frailty and its effect on recovery from
      critical illness and its potential to modify the course of patient care will be
      important areas of research in the future. 

PMID- 26315638
TI  - Pain Management Issues for the Geriatric Surgical Patient.
AB  - Adequate treatment of pain is of utmost importance in making uncomplicated the
      perioperative course for geriatric surgical patients. Effective analgesia reduces
      morbidity, improves patient and family satisfaction, and is a natural expectation
      of high-quality care. Pain treatment in older adults is more complicated than in
      younger counterparts, and great consideration must be given to age-related
      changes in physiology and pharmacokinetics. Pain treatment must be individualized
      based on each patient's profile. Side effects must be minimized and organ
      toxicity avoided. When complications occur they may be more severe, and treatment
      must be prompt. Alternative plans for analgesia must be readily enacted. 

PMID- 26315639
TI  - Chronic Pain in Older Adults.
AB  - This review summarizes existing evidence relevant to the epidemiology of chronic
      pain in older adults, age-related differences relevant to pain, pain assessment,
      and important considerations regarding pain management in later life. Features
      unique to pain assessment in older adults include the likelihood of multiple
      diagnoses contributing to chronic pain, the ability of older adults to self
      report, including those with mild to moderate cognitive impairment, and
      recognition that some older adults with cognitive impairment may demonstrate
      various behaviors to communicate pain. Management is best accomplished through a
      multimodal approach, including pharmacologic and nonpharmacologic treatments,
      physical rehabilitation, and psychological therapies. Interventional pain
      therapies may be appropriate in select older adults, which may reduce the need
      for pharmacologic treatments. 

PMID- 26315640
TI  - Palliative Care for the Geriatric Anesthesiologist.
AB  - Many seriously ill geriatric patients are at higher risk for perioperative
      morbidity and mortality, and incorporating proactive palliative care principles
      may be appropriate. Advanced care planning is a hallmark of palliative care in
      that it facilitates alignment of the goals of care between the patient and the
      health care team. When these goals conflict, perioperative dilemmas can occur.
      Anesthesiologists must overcome many cultural and religious barriers when
      managing the care of these patients. Palliative care is gaining ground in several
      perioperative populations where integration with certain patient groups has
      occurred. Geriatric anesthesiologists must be aware of how palliative care and
      hospice influence and enhance the care of elderly patients. 

PMID- 26315636
TI  - Postoperative Cognitive Dysfunction: Minding the Gaps in Our Knowledge of a
      Common Postoperative Complication in the Elderly.
AB  - Postoperative cognitive dysfunction (POCD) is a common complication associated
      with significant morbidity and mortality in elderly patients. There is much
      interest in and controversy about POCD, reflected partly in the increasing number
      of articles published on POCD recently. Recent work suggests surgery may also be
      associated with cognitive improvement in some patients, termed postoperative
      cognitive improvement (POCI). As the number of surgeries performed worldwide
      approaches 250 million per year, optimizing postoperative cognitive function and
      preventing/treating POCD are major public health issues. In this article, we
      review the literature on POCD and POCI, and discuss current research challenges
      in this area. 

PMID- 26315641
TI  - Geriatric Anesthesia: Can We Achieve the Goal of Returning our Elderly to
      Baseline or Improved Function?

PMID- 26315642
TI  - Optimizing Perioperative Care for Older Adults.

PMID- 26315643
TI  - Unilateral Psoriatic Arthritis in Hemiparesis.

PMID- 26315646
TI  - [Suicidal behavior: a psychiatric emergency situation, suicide prevention: a
      psychiatric obligation].
AB  - In German psychiatry suicidal behavior is seen as sign of a psychiatric crisis in
      a person in the context of psychopathology, psychodynamics and psychosocial
      situation. Psychiatric disorders are found in up to 90% of people who commit
      suicide and the time span following the decision to commit suicide is often very
      short, within 24 h. Suicide prevention is a central duty and obligation in
      psychiatry and psychotherapy. This article gives an overview on the current state
      of knowledge on suicide from a clinical point of view.

PMID- 26315647
TI  - Real-time terahertz digital holography with a quantum cascade laser.
AB  - Coherent imaging in the THz range promises to exploit the peculiar capabilities
      of these wavelengths to penetrate common materials like plastics, ceramics, paper
      or clothes with potential breakthroughs in non-destructive inspection and quality
      control, homeland security and biomedical applications. Up to now, however, THz
      coherent imaging has been limited by time-consuming raster scanning, point-like
      detection schemes and by the lack of adequate coherent sources. Here, we
      demonstrate real-time digital holography (DH) at THz frequencies exploiting the
      high spectral purity and the mW output power of a quantum cascade laser combined
      with the high sensitivity and resolution of a microbolometric array. We show
      that, in a one-shot exposure, phase and amplitude information of whole samples,
      either in reflection or in transmission, can be recorded. Furthermore, a 200
      times reduced sensitivity to mechanical vibrations and a significantly enlarged
      field of view are observed, as compared to DH in the visible range. These
      properties of THz DH enable unprecedented holographic recording of real world
      dynamic scenes. 

PMID- 26315648
TI  - Characteristics associated with sexual assaults at mass gatherings.
AB  - INTRODUCTION: Sexual assault is disturbingly common, yet little is known about
      those occurring at mass gatherings, defined as a group of people congregated for
      a common purpose. Our objectives were to examine patterns of variation in sexual
      assault associated with mass gatherings and to determine factors associated with
      assaults occurring at mass gatherings. METHODS: We performed a case series
      analysis from January to December, 2013. We included all patients >16 years
      presenting within 30 days of their sexual assault to the Ottawa Hospital Sexual
      Assault and Partner Abuse Care Program (SAPACP). Cases were stratified by whether
      or not they occurred at mass gatherings. We abstracted from the SAPACP records:
      patient and sexual assault characteristics, alcohol or drug consumption and
      medical and forensic care accepted. We performed descriptive analyses and
      multiple logistical regression to identify factors associated with mass gathering
      assaults. RESULTS: We found 204 cases of sexual assault, of which 53 (26%)
      occurred at mass gatherings. Relative frequencies of mass gathering sexual
      assaults peaked during New Year's Eve, Canada Day, university frosh week and
      Halloween. We found the following factors were statistically significantly
      associated with sexual assault at mass gatherings: younger age (OR=0.95, 95% CI
      0.91 to 0.99); voluntary consumption of drugs and alcohol (3.88, 95% CI 1.34 to
      11.23); assault occurring on a holiday (2.37, 95% CI 1.00 to 5.64) and the
      assailant unknown to the victim (2.43, 95% CI 1.15 to 5). INTERPRETATION: This
      study is the first to describe patterns of variation in sexual assault incidents
      associated with occurrence of mass gatherings as well as factors associated with
      such assaults. We will disseminate these results to key stakeholders in order to
      develop prevention-minded policies for future mass gatherings.

PMID- 26315649
TI  - A systems biology approach identifies new regulators of poplar root development
      under low nitrogen.
AB  - In Populus, low nitrogen (LN) elicits rapid and vigorous lateral root (LR)
      proliferation, which is closely mirrored by corresponding transcriptomic changes.
      Using transcriptomic data, we built a genetic network encompassing a large
      proportion of the differentially regulated transcriptome. The network is
      organized in a hierarchical fashion, centered on 11 genes. Transgenic
      manipulations of only three of the 11 genes had a strong impact on root
      development under LN. These three genes encoded an F-box protein similar to
      Hawaiian Skirt (PtaHWS) and two transcription factors (PtaRAP2.11 and PtaNAC1).
      Up- and downregulation of the three genes caused increased and decreased root
      proliferation under LN conditions, respectively. The transgenic manipulations had
      a strong positive effect on growth under greenhouse conditions including
      increased shoot and root biomass. The three genes appeared to encompass a
      putative yet-unknown mechanism that underlies root development under LN.
      Specifically, the genes are predominantly expressed in roots and have a similar
      temporal response to LN. More importantly, transgenic manipulation for each of
      the three genes had a highly significant impact on the expression of the other
      two. The transgenic manipulations appear to also affect the expression of the
      regulatory miRNA (PtamiRNA164e) of one of the transcription factors (PtaNAC1),
      albeit in an opposite fashion. Consistent with a putative function of PtaHWS in
      proteasome degradation, treatment with proteasome inhibitor reversed the
      expression changes in the transgenic plants. The insights from this study will
      allow genetic modifications of root architecture for more efficient and dynamic
      nitrogen foraging in biofuel crops like poplar. 

PMID- 26315650
TI  - [Rural medical practice at the beginning of the 20th century. Martinez Saldise
      (1855-1937), honorary member of Paediatric Society of Madrid in 1927].
AB  - INTRODUCTION: On the centenary of the foundation of the Paediatrics Society of
      Madrid, a tribute is presented to rural medical practice of that time, although
      there are few documents on the history of rural medicine. The main objective is
      to describe the context of the rural medical practice in the late 19th and
      beginning 20th century, while presenting a historical biographical review of
      Manuel Martinez Saldise, who was medical specialist from Cazalegas (Toledo). He
      was appointed an Honorary Member by the Paediatrics Society of Madrid in 1927.
      MATERIAL AND METHODS: A search was carried out in repositories of digitized
      media, web portals of history of medicine, PubMed, IME files of local councils
      and medical colleges. The family archives were reviewed with the collaboration of
      his descendants. RESULTS: The hiring of rural doctors was carried out by the
      municipalities, and the salary largely depended on private practice as well as
      "retainers". Specialist physicians took part in epidemics, legal medicine, and in
      hygiene measures. They also had disputes with mayors, chiefs, with colleagues and
      with protectionism. A summary of the biography and occupational activity of
      Manuel Martinez Saldise is presented. COMMENTS: Rural doctors were subjected to
      the society of their time, with the issues that arose, denouncing the
      shortcomings of the local administrations, dedicated efforts to their family and
      the most disadvantaged.

PMID- 26315651
TI  - Report of the international conference on regulatory endeavors towards the sound
      development of human cell therapy products.
AB  - The regulation of human cell therapy products is a key factor in their
      development and use to treat human diseases. In that regard, there is a
      recognized need for a global effort to develop a set of common principles that
      may serve to facilitate a convergence of regulatory approaches to ensure the
      smooth and efficient evaluation of products. This conference, with experts from
      regulatory agencies, industry, and academia, contributed to the process of
      developing such a document. Elements that could form a minimum consensus package
      of requirements for evaluating human cell therapy products were the overall focus
      of the conference. The important regulatory considerations that are unique to
      human cell therapy products were highlighted. Sessions addressed specific points
      that are different from those of traditional biological/biotechnological protein
      products. Panel discussions complemented the presentations. The conference
      concluded that most of the current regulatory framework is appropriate for cell
      therapy, but there are some areas where the application of the requirements for
      traditional biologicals is inappropriate. In addition, it was agreed that there
      is a need for international consensus on core regulatory elements, and that one
      of the major international organizations should take the lead in formulating such
      a consensus document. 

PMID- 26315652
TI  - Impact of National and International Stem Cell Banking Initiatives on progress in
      the field of cell therapy: IABS-JST Joint Workshop: Summary for Session 5.
AB  - In order to assure the quality and safety of future advanced cell therapies it is
      vital to ensure that source materials including the donor cells have been
      assessed and demonstrated as suitable for use in the development and manufacture
      of such new medicines. Here we provide a brief overview of the key issues in the
      delivery of quality controlled and safety tested seed stocks of human pluripotent
      stem cell lines to support stem cell research and the development of advanced
      cell therapies. We also reflect on the importance of national and internationally
      coordinated cell banking systems in this process in order to promote more
      efficient development of cell therapies. 

PMID- 26315653
TI  - Protocolized sedation effect on post-ICU posttraumatic stress disorder
      prevalence: A systematic review and network meta-analysis.
AB  - PURPOSE: Strategies aiming light sedation are associated with decreased length on
      mechanical ventilation. However, awake or easily arousable patients may be prone
      to greater prevalence of posttraumatic stress disorder (PTSD). These systematic
      review and meta-analysis aimed to evaluate the safety of light sedation
      strategies regarding the prevalence of PTSD. METHODS: We searched MEDLINE,
      Scopus, and Web of Science from inception to November 2014 for randomized
      controlled trials that evaluated light sedation strategies and addressed PTSD
      prevalence in the follow-up as a specific outcome. Because not all trials
      performed the same comparisons, we performed a network meta-analysis to evaluate
      indirect comparisons. RESULTS: Five studies fulfilled our inclusion criteria and
      were included in the meta-analysis. Two studies compared daily sedation
      interruption with usual care (92 patients), 2 studies compared a light sedation
      protocol with daily sedation interruption (47 patients), and 1 study compared
      light and deep sedation (102 patients). Compared with usual sedation care/deep
      sedation, neither daily interruption of sedation (odds ratio=0.66; 95% confidence
      interval, 0.22-1.98) nor a light sedation protocol (odds ratio=0.90, 95%
      confidence interval, 0.27-3.05) was associated with increased risks on long-term
      PTSD prevalence. CONCLUSION: Light sedation strategies seem to be safe in terms
      of PTSD prevalence. However, the small number of included trials and patients may
      not be sufficient to drive strong statements.

PMID- 26315654
TI  - The Surgical Optimal Mobility Score predicts mortality and length of stay in an
      Italian population of medical, surgical, and neurologic intensive care unit
      patients.
AB  - PURPOSE: We validated the Italian version of Surgical Optimal Mobility Score
      (SOMS) and evaluated its ability to predict intensive care unit (ICU) and
      hospital length of stay (LOS), and hospital mortality in a mixed population of
      ICU patients. MATERIALS AND METHODS: We applied the Italian version of SOMS in a
      consecutive series of prospectively enrolled, adult ICU patients. Surgical
      Optimal Mobility Score level was assessed twice a day by ICU nurses and twice a
      week by an expert mobility team. Zero-truncated Poisson regression was used to
      identify predictors for ICU and hospital LOS, and logistic regression for
      hospital mortality. All models were adjusted for potential confounders. RESULTS:
      Of 98 patients recruited, 19 (19.4%) died in hospital, of whom 17 without and 2
      with improved mobility level achieved during the ICU stay. SOMS improvement was
      independently associated with lower hospital mortality (odds ratio, 0.07; 95%
      confidence interval [CI], 0.01-0.42) but increased hospital LOS (odds ratio,
      1.21; 95% CI: 1.10-1.33). A higher first-morning SOMS on ICU admission,
      indicating better mobility, was associated with lower ICU and hospital LOS (rate
      ratios, 0.89 [95% CI, 0.80-0.99] and 0.84 [95% CI, 0.79-0.89], respectively).
      CONCLUSIONS: The first-morning SOMS on ICU admission predicted ICU and hospital
      LOS in a mixed population of ICU patients. SOMS improvement was associated with
      reduced hospital mortality but increased hospital LOS, suggesting the need of
      optimizing hospital trajectories after ICU discharge.

PMID- 26315655
TI  - Altered mental status in the neurocritical care unit.
AB  - Altered mental status is a common pathological entity in critically ill patients
      and particularly in those with preexisting cerebral injury. In the neurological
      critical care unit, the prevalence of altered mental status is especially high
      because of the inherent nervous system disease of these patients. Altered mental
      status can be crudely divided into encephalopathy and delirium. Although often
      used interchangeably, the 2 pathological entities have subtle differences in
      etiology and presentation. This is a review of delirium and encephalopathy in the
      neurological critical care unit. 

PMID- 26315656
TI  - The difficulties of designing a broadly accepted PLMS scoring algorithm.

PMID- 26315657
TI  - Photo-induced H2 production from a CH3OH-H2O solution at insulator surface.
AB  - In a conventional photocatalytic or photochemical process, either a photocatalyst
      or a molecule is excited by irradiation light that has energy greater than the
      forbidden band (i.e., the band gap) of the semiconductor or the transition energy
      of an excited state of the molecule, respectively, for a reaction to occur.
      However, in this work, we found that a considerable amount of H2 can be generated
      from a CH3OH-H2O solution at a quartz surface using light with energy far outside
      the electronic absorbance range of the CH3OH-H2O solution; this process should
      not occur in principle via either conventional photocatalysis or a photochemical
      process. The H2 production was further confirmed using 266 nm and 355 nm lasers
      as light sources. Our work demonstrates that photo-induced H2 production can
      occur on insulator surfaces (e.g., quartz), which were commonly believed to be
      inert, and will shed light on the surface nature of insulators. 

PMID- 26315658
TI  - Atypical Findings on Cervicovaginal Smears Correlate with Cervical Involvement by
      Malignant Mixed Mullerian Tumors of the Uterus.
AB  - OBJECTIVE: A malignant mixed mullerian tumor (MMMT) is a high-grade neoplasm
      commonly arising from the uterus. Patients present with bleeding and a mass
      protruding from the cervix. This study was designed to correlate Papanicolaou
      (Pap) smear findings with histological findings in women diagnosed with MMMT.
      STUDY DESIGN: Women diagnosed with MMMT were identified. Preoperative Pap tests
      were correlated with histological findings. Statistical analysis was performed to
      assess associations between abnormal Pap tests and histological findings.
      RESULTS: Forty patients with MMMT were included in the study. Age ranged from 37
      85 years and tumor size ranged from 1.2 to 21 cm. In presurgical Pap tests (4
      conventional and 36 liquid based), 11 smears (27.5%) were diagnosed as negative,
      5 (12.5%) as atypical squamous cells of undetermined significance, 6 (15%) as
      atypical glandular cells, 16 (40%) as malignant and 2 (5%) as high-grade squamous
      intraepithelial lesion. Malignant cells detected on Pap smears showed a strong
      correlation with endocervical involvement by MMMT (p = 0.002). Larger tumors were
      more likely to involve the cervix (p = 0.0115). CONCLUSIONS: The Pap test can
      predict cervical involvement by MMMT. On Pap smears, MMMT cells showed no
      correlation with other adverse histological features (lymphovascular invasion,
      myoinvasion or adnexal involvement).

PMID- 26315659
TI  - Skin and Environmental Contamination in Patients Diagnosed With Clostridium
      difficile Infection but Not Meeting Clinical Criteria for Testing.
AB  - Of 134 patients diagnosed with Clostridium difficile infection, 30 (22%) did not
      meet clinical criteria for testing because they lacked significant diarrhea or
      had alternative explanations for diarrhea and no recent antibiotic exposure. For
      these patients, skin and/or environmental contamination was common only in those
      with prior antibiotic exposure.

PMID- 26315660
TI  - CAVEOLIN-1 expression in brain metastasis from lung cancer predicts worse outcome
      and radioresistance, irrespective of tumor histotype.
AB  - Brain metastases develop in one-third of patients with non-small-cell lung cancer
      and are associated with a dismal prognosis, irrespective of surgery or chemo
      radiotherapy. Pathological markers for predicting outcomes after surgical
      resection and radiotherapy responsiveness are still lacking. Caveolin 1 has been
      associated with chemo- and radioresistance in various tumors, including non-small
      cell lung cancer. Here, caveolin 1 expression was assessed in a series of 69
      brain metastases from non-small-cell lung cancer and matched primary tumors to
      determine its role in predicting survival and radiotherapy responsiveness. Only
      caveolin 1 expression in brain metastasis was associated with poor prognosis and
      an increased risk of death (log rank test, p = 0.015). Moreover, in the younger
      patients (median age of <54 years), caveolin 1 expression neutralized the
      favorable effect of young age on survival compared with the older patients. Among
      the radiotherapy-treated patients, an increased risk of death was detected in the
      group with caveolin 1-positive brain metastasis (14 out of 22 patients, HR=6.839,
      95% CI 1.849 to 25.301, Wald test p = 0.004). Overall, caveolin 1 expression in
      brain metastasis from non-small-cell lung cancer is independently predictive of
      worse outcome and radioresistance and could become an additional tool for
      personalized therapy in the critical subset of brain-metastatic non-small-cell
      lung cancer patients. 

PMID- 26315661
TI  - Estimating the cost of referral and willingness to pay for referral to higher
      level health facilities: a case series study from an integrated community case
      management programme in Uganda.
AB  - BACKGROUND: Integrated community case management (iCCM) relies on community
      health workers (CHWs) managing children with malaria, pneumonia, diarrhoea, and
      referring children when management is not possible. This study sought to
      establish the cost per sick child referred to seek care from a higher-level
      health facility by a CHW and to estimate caregivers' willingness to pay (WTP) for
      referral. METHODS: Caregivers of 203 randomly selected children referred to
      higher-level health facilities by CHWs were interviewed in four Midwestern Uganda
      districts. Questionnaires and document reviews were used to capture direct,
      indirect and opportunity costs incurred by caregivers, CHWs and health facilities
      managing referred children. WTP for referral was assessed through the 'bidding
      game' approach followed by an open-ended question on maximum WTP. Descriptive
      analysis was conducted for factors associated with referral completion and WTP
      using logistic and linear regression methods, respectively. The cost per case
      referred to higher-level health facilities was computed from a societal
      perspective. RESULTS: Reasons for referral included having fever with a negative
      malaria test (46.8%), danger signs (29.6%) and drug shortage (37.4%). Among the
      referred, less than half completed referral (45.8%). Referral completion was 2.8
      times higher among children with danger signs (p = 0.004) relative to those
      without danger signs, and 0.27 times lower among children who received pre
      referral treatment (p < 0.001). The average cost per case referred was US$ 4.89
      and US$7.35 per case completing referral. For each unit cost per case referred,
      caregiver out of pocket expenditure contributed 33.7%, caregivers' and CHWs'
      opportunity costs contributed 29.2% and 5.1% respectively and health facility
      costs contributed 39.6%. The mean (SD) out of pocket expenditure was US$1.65
      (3.25). The mean WTP for referral was US$8.25 (14.70) and was positively
      associated with having received pre-referral treatment, completing referral and
      increasing caregiver education level. CONCLUSION: The mean WTP for referral was
      higher than the average out of pocket expenditure. This, along with suboptimal
      referral completion, points to barriers in access to higher-level facilities as
      the primary cause of low referral. Community mobilisation for uptake of referral
      is necessary if the policy of referring children to the nearest health facility
      is to be effective.

PMID- 26315662
TI  - CRFs based de-identification of medical records.
AB  - De-identification is a shared task of the 2014 i2b2/UTHealth challenge. The
      purpose of this task is to remove protected health information (PHI) from medical
      records. In this paper, we propose a novel de-identifier, WI-deId, based on
      conditional random fields (CRFs). A preprocessing module, which tokenizes the
      medical records using regular expressions and an off-the-shelf tokenizer, is
      introduced, and three groups of features are extracted to train the de-identifier
      model. The experiment shows that our system is effective in the de-identification
      of medical records, achieving a micro-F1 of 0.9232 at the i2b2 strict entity
      evaluation level. 

PMID- 26315663
TI  - Numerical study of the effect of the nasal cycle on unilateral nasal resistance.
AB  - We used computational fluid dynamics to study the effects of the nasal cycle on
      the modification of unilateral nasal resistance using nasal cavity models from 2
      different patients with chronic rhinosinusitis. A steady airflow field with an
      inspiratory flow rate of 250 mL/s was simulated using ANSYS-FLUENT v14.5. The
      distribution of local unilateral nasal resistance showed different shapes of
      variation and magnitudes of resistance depending on the distribution of cross
      sectional area in the nasal cavity models. The highest local resistance on the
      congested side was found near the nasal valve area in the first patient, whereas
      the highest value was found in the nasal vestibule for the second patient. The
      relative importance of nasal resistance in the turbinated air passage differed
      for the 2 patients. The unilateral resistance of the congested state was in the
      range of 0.0229-0.221 Pas/mL. In the inferior meatus, greater flow rate was
      allowed during the congested state than during the decongested state if an
      extensive backflow developed.

PMID- 26315664
TI  - Non-suicidal self-injury with and without borderline personality disorder:
      differences in self-injury and diagnostic comorbidity.
AB  - Although non-suicidal self-injury (NSSI) occurs in people with and without
      borderline personality disorder (BPD), few studies have compared the clinical
      characteristics of these two groups. The present study sampled adults with a
      history of NSSI and compared those with and without BPD on (a) NSSI features, (b)
      co-occurring psychiatric disorders, and (c) severity of depression, suicidal
      ideation and emotion dysregulation. Participants (NSSI+BPD, n=46; NSSI Only,
      n=54) completed semi-structured interviews and self-report measures. Whereas the
      groups did not differ in age of NSSI onset, the NSSI+BPD group engaged in more
      frequent, recent and severe NSSI, and reported higher rates of skin carving, head
      banging, self-punching and self-scratching than the NSSI Only group. Participants
      with BPD also showed greater diagnostic comorbidity, particularly for anxiety
      disorders, but did not differ from participants without BPD in rates of mood,
      substance or psychotic disorders. The NSSI+BPD group reported more severe
      depressive symptomatology, suicidal ideation and emotion dysregulation than the
      NSSI Only group. Supplementary analyses on the subset of participants with recent
      (past year) NSSI revealed similarly medium to large differences between those
      with and without BPD. Implications for assessment and treatment are discussed. 

PMID- 26315665
TI  - Parents' personality clusters and eating disordered daughters' personality and
      psychopathology.
AB  - The present study explores how parents' personality clusters relate to their
      eating disordered daughters' personality and psychopathology. Mothers and fathers
      were tested with the Temperament Character Inventory. Their daughters were
      assessed with the following: Temperament and Character Inventory, Eating Disorder
      Inventory-2, Symptom Checklist-90, Parental Bonding Instrument, Attachment Style
      Questionnaire, and Family Assessment Device. Daughters' personality traits and
      psychopathology scores were compared between clusters. Daughters' features were
      related to those of their parents. Explosive/adventurous mothers were found to
      relate to their daughters' borderline personality profile and more severe
      interoceptive awareness. Mothers' immaturity was correlated to their daughters'
      higher character immaturity, inadequacy, and depressive feelings. Fathers who
      were explosive/methodic correlated with their daughters' character immaturity,
      severe eating, and general psychopathology. Fathers' character immaturity only
      marginally related to their daughters' specific features. Both parents'
      temperament clusters and mothers' character clusters related to patients'
      personality and eating psychopathology. The cluster approach to personality
      related dynamics of families with an individual affected by an eating disorder
      expands the knowledge on the relationship between parents' characteristics and
      daughters' illness, suggesting complex and unique relationships correlating
      parents' personality traits to their daughters' disorder. 

PMID- 26315666
TI  - Implementing Major Trauma Audit in Ireland.
AB  - BACKGROUND: There are 27 receiving trauma hospitals in the Republic of Ireland.
      There has not been an audit system in place to monitor and measure processes and
      outcomes of care. The National Office of Clinical Audit (NOCA) is now working to
      implement Major Trauma Audit (MTA) in Ireland using the well-established National
      Health Service (NHS) UK Trauma Audit and Research Network (TARN). AIMS: The aim
      of this report is to highlight the implementation process of MTA in Ireland to
      raise awareness of MTA nationally and share lessons that may be of value to other
      health systems undertaking the development of MTA. METHODS: The National Trauma
      Audit Committee of the Royal College of Surgeons in Ireland, consisting of
      champions and stakeholders in trauma care, in 2010 advised on the adaptation of
      TARN for Ireland. In 2012, the Emergency Medicine Program endorsed TARN and in
      setting up the National Emergency Medicine Audit chose MTA as the first audit
      project. A major trauma governance group was established representing
      stakeholders in trauma care, a national project co-ordinator was recruited and a
      clinical lead nominated. Using Survey Monkey, the chief executives of all trauma
      receiving hospitals were asked to identify their hospital's trauma governance
      committee, trauma clinical lead and their local trauma data co-ordinator.
      Hospital Inpatient Enquiry systems were used to identify to hospitals an estimate
      of their anticipated trauma audit workload. RESULTS: There are 25 of 27 hospitals
      now collecting data using the TARN trauma audit platform. These hospitals have
      provided MTA Clinical Leads, allocated data co-ordinators and incorporated MTA
      reports formally into their clinical governance, quality and safety committee
      meetings. There has been broad acceptance of the NOCA escalation policy by
      hospitals in appreciation of the necessity for unexpected audit findings to
      stimulate action. CONCLUSION: Major trauma audit measures trauma patient care
      processes and outcomes of care to drive quality improvement at hospital and
      national level. MTA will facilitate the strategic development of trauma care in
      Ireland by monitoring processes and outcomes and the effects of changes in trauma
      service provision.

PMID- 26315667
TI  - Plate fixation versus conservative treatment of displaced midshaft clavicle
      fractures: Functional outcome and patients' satisfaction during a mean follow-up
      of 5 years.
AB  - INTRODUCTION: The aim of the present prospective clinical trial was to compare
      patient-oriented and surgeon-based outcomes after non-operative care with
      operative treatment of displaced midshaft clavicle fractures. PATIENTS/METHODS:
      Between January 2009 and July 2011, 97 consecutive patients presenting with a
      midshaft clavicle fracture were prospectively recorded and included in this
      study. The patients were placed in either of the treatment groups on their own
      preference. They were then seen in outpatient clinic at two, six and 24 weeks
      were all endpoints were investigated and motivation of choice of treatment was
      noted. Study follow-up was continued until Augustus 2014, being the time point
      that long-term functional outcome was measured through a DASH score by letter.
      RESULTS: 97 patients were included in the functional outcome analysis. The mean
      DASH and Constant scores were significant better in the operative (90.9+/-14.2
      and 15.7+/-17.2) than in the conservative treatment group at six weeks (78.7+/
      17.0 and 24.8+/-16.7). There was a significant improvement in the Constant
      (95.9+/-10.5 versus 94.5+/-5.9) and DASH scores (8.8+/-12.0 versus 7.1+/-10.7)
      for both groups at 24 weeks but there was no significant difference in functional
      scores between the groups. Four patients developed a non-union, one patient in
      the operative and three patients in the conservative group. Overall complications
      were significantly higher in the operative group (31%) compared to the
      conservative group (9%) (p<0.001). There was no significant difference in long
      term functional outcome between the two treatment groups (5.2+/-9.8 versus 2.5+/
      4.9 p=0.12). Patient's satisfaction was higher in the operative than in the
      conservative group (p<0.04). CONCLUSION: Significant superior outcome scores were
      seen at six weeks for the operative group. However, at 24 weeks and 5-year follow
      up no difference was seen in functional outcome scores for both treatment groups.
      Therefore, the challenge for the future is to better identify the subgroup of
      patients who might benefit from primary surgical intervention.

PMID- 26315668
TI  - Role of DetR in defence is critical for virulence of Xanthomonas oryzae pv.
      oryzae.
AB  - Like other bacteria, Xanthomonas oryzae pv. oryzae (Xoo), the causal agent of
      bacterial leaf blight disease in rice, possesses intracellular signalling
      systems, known as two-component regulatory systems (TCSs), which regulate
      pathogenesis and biological processes. Completion of the genome sequences of
      three Xoo strains has facilitated the functional study of genes, including those
      of TCSs, but the biological functions of most Xoo TCSs have not yet been
      uncovered. To identify TCSs involved in Xoo pathogenesis, we generated knockout
      strains lacking response regulators (RRs, a cytoplasmic signalling component of
      the TCS) and examined the virulence of the RR knockout strains. This study
      presents a knockout strain (detR(-) ) lacking the PXO_04659 gene which shows
      dramatically reduced virulence relative to the wild-type. Our studies to
      elucidate detR function in Xoo pathogenesis revealed a reduction in extracellular
      polysaccharide (EPS), intolerance to reactive oxygen species (ROS) and
      deregulation of iron homeostasis in the detR(-) strain. Moreover, gene expression
      of regulatory factors, including other RRs and transcription factors (TFs), was
      altered in the absence of DetR protein, as determined by reverse transcription
      polymerase chain reaction (RT-PCR) and/or real-time quantitative RT-PCR analyses.
      All evidence leads to the conclusion that DetR is essential for Xoo virulence
      through the regulation of the Xoo defence system including EPS synthesis, ROS
      detoxification and iron homeostasis, solely or cooperatively with other
      regulatory factors. 

PMID- 26315669
TI  - Utility of diabetes-associated autoantibodies for classification of new onset
      diabetes in children and adolescents.
AB  - OBJECTIVE: To determine whether measuring diabetes-associated autoantibodies
      (DAA) in pediatric new onset diabetes (NODM) can be restricted to patients with
      equivocal diabetes type. RESEARCH DESIGN AND METHODS: Retrospective analysis of
      all patients with NODM admitted to Boston Children's Hospital from 1 October 2007
      to 1 July 2013 who had measurement of DAA [glutamic acid decarboxylase, insulin,
      insulinoma-associated antigen 2 (IA-2)]. Data collection included initial
      diagnosis of diabetes type before DAA results and at follow-up. We used logistic
      regression to predict type 1 diabetes (T1D) and developed a clinical score to
      classify diabetes type. RESULTS: Of 1089 patients (45.4% female, 76.7% White, age
      10.6 +/- 4.5 yr), initial diagnosis was 1021 (93.8%) T1D, 42 (3.9%) type 2
      diabetes (T2D), and 26 (2.4%) other. Of 993 patients with clinical T1D, 78 (7.9%)
      were DAA-, and of 42 patients with clinical T2D, 12 (28.6%) were DAA+. Type of
      diabetes was reclassified at follow-up in less than 6% of patients. Data from a
      subset of 736 patients were used to develop a scoring system to predict T1D.
      Using weight z-score, age, and race, the scoring system had 91.7% sensitivity,
      82% specificity, and a positive predictive value of 98.6%, and suggested DAA
      measurement was unnecessary in 85.3% of patients. Findings were similar in a
      validation cohort of 234 patients. CONCLUSIONS: Application of a simple scoring
      system may reduce to ~15% the number of DAA measurements needed to classify
      diabetes type, resulting in substantial cost savings. Clinical judgment should
      guide the decision to measure DAA.

PMID- 26315671
TI  - Circulating Nucleic Acids Special Issue.

PMID- 26315670
TI  - Poisoning emergency visits among children: a 3-year retrospective study in Qatar.
AB  - BACKGROUND: Poisoning in toddlers and infants is almost always unintentional due
      to their exploratory behavior, which is different from adults. The prevalence and
      background of childhood poisoning in Qatar is still unknown. The aim of this
      study is to explore the extent of childhood poisoning in Qatar and, specifically,
      to describe the frequency of poisoning as a cause of Accident & Emergency (A&E)
      admission, the demographic profile of affected patients, the circumstances
      leading to exposure, and the specific agents involved in poisoning among children
      under age 14 in our setting. METHODS: This study was a cross-sectional survey of
      children up to 14 years old utilizing retrospective data between October 2009 and
      October 2012. The data were collected from the childhood poisoning case registry
      and patient medical records at the Accident and Emergency (A&E) Unit of all the
      Hamad Medical Corporation hospitals. Pharmacists reviewed all the handwritten
      medical records. Data written on the data collection form were transferred into
      excel and later into SPSS version 21. The data were analyzed using frequencies
      and percentages, and a chi-square test was used for categorical variables.
      RESULTS: Out of 1179 registered poisoning cases listed in the registry, only 794
      cases (67.3%) were usable and included in the final analysis. A&E admissions for
      unintentional poisoning for children accounted for 0.22% of all A&E admissions
      from 2009 to 12. The majority of poisoning cases happened among children between
      1 and 5 years old (n = 704, 59.7%). Cases were more frequent among non-Qatari
      than Qatari children (39.4% vs. 28.5%). Most cases occurred in the living room
      (28.2%) and typically took place in the afternoon (29.2%). Analgesic and
      antipyretic medicines were the most common agents ingested by children (n = 194,
      36.9%), specifically paracetamol (n = 140, 26.6%). CONCLUSIONS: Cases of
      unintentional poisoning are higher among children aged 1 to 5 years, males and
      non-Qatari. Most cases occurred in the living room and typically took place in
      the afternoon. The most common type of poison ingested by children was medicines,
      i.e., analgesics and antipyretics, specifically paracetamol.

PMID- 26315672
TI  - Hyperbolic polaritonic crystals based on nanostructured nanorod metamaterials.
AB  - Surface plasmon polaritons usually exist on a few suitable plasmonic materials;
      however, nanostructured plasmonic metamaterials allow a much broader range of
      optical properties to be designed. Here, bottom-up and top-down nanostructuring
      are combined, creating hyperbolic metamaterial-based photonic crystals termed
      hyperbolic polaritonic crystals, allowing free-space access to the high spatial
      frequency modes supported by these metamaterials. 

PMID- 26315674
TI  - Identification of Akt1 as a potent therapeutic target for oral squamous cell
      carcinoma.
AB  - Oncogene addiction can provide therapeutic opportunities in human malignancies.
      In this study, we aimed to identify critical oncogenes for oral squamous cell
      carcinoma (OSCC) development and progression. We determined gene expression
      profiles in 10 primary OSCCs and 10 human OSCC cell lines using Applied
      Biosystems Human Genome Survey Arrays. Akt1 was the only gene identified that was
      expressed in all OSCC tissues and cultured cells, but not in non-neoplastic
      tissues and cells. Subsequently, western blot analysis showed that Akt1 protein
      was overexpressed in OSCC tissues and cell lines. Immunohistochemistry also
      showed Akt1 protein expression in 59 of 63 (94%) primary OSCCs. To clarify the
      oncogenic function of Akt1 in human OSCC cells, we used RNA interference. We
      designed and synthesized 5 small interfering RNAs specific for Akt1 (siAkt1).
      Transfecting human OSCC cells with siAkt1 in vitro markedly suppressed their
      expression of Akt1 protein and significantly reduced their growth rate.
      Furthermore, the growth of human OSCC tumors which had been subcutaneously
      xenografted in athymic nude mice lacking interferon responses was markedly
      inhibited by atelocollagen-mediated systemic siAkt1 administration. We also found
      that synthetic siAkt1 had an inhibitory effect on the growth of primary cultured
      OSCC cells. Finally, we investigated the molecular mechanisms involved in the
      growth inhibitory effect of Akt1 suppression using microarray analysis of human
      OSCC cells transfected with siAkt1. Knockdown of Akt1 induced the expression of
      CDKN2B, a tumor suppressor gene, and reduced the expression of TGFBR1, which
      supports malignant phenotypes. These results suggest that Akt1 functions as a
      critical oncogene in human OSCC cells and may therefore be an appropriate target
      for novel OSCC therapies.

PMID- 26315673
TI  - Chronic mTOR inhibition in mice with rapamycin alters T, B, myeloid, and innate
      lymphoid cells and gut flora and prolongs life of immune-deficient mice.
AB  - The mammalian (mechanistic) target of rapamycin (mTOR) regulates critical immune
      processes that remain incompletely defined. Interest in mTOR inhibitor drugs is
      heightened by recent demonstrations that the mTOR inhibitor rapamycin extends
      lifespan and healthspan in mice. Rapamycin or related analogues (rapalogues) also
      mitigate age-related debilities including increasing antigen-specific immunity,
      improving vaccine responses in elderly humans, and treating cancers and
      autoimmunity, suggesting important new clinical applications. Nonetheless, immune
      toxicity concerns for long-term mTOR inhibition, particularly immunosuppression,
      persist. Although mTOR is pivotal to fundamental, important immune pathways,
      little is reported on immune effects of mTOR inhibition in lifespan or healthspan
      extension, or with chronic mTOR inhibitor use. We comprehensively analyzed immune
      effects of rapamycin as used in lifespan extension studies. Gene expression
      profiling found many and novel changes in genes affecting differentiation,
      function, homeostasis, exhaustion, cell death, and inflammation in distinct T-
      and B-lymphocyte and myeloid cell subpopulations. Immune functions relevant to
      aging and inflammation, and to cancer and infections, and innate lymphoid cell
      effects were validated in vitro and in vivo. Rapamycin markedly prolonged
      lifespan and healthspan in cancer- and infection-prone mice supporting disease
      mitigation as a mechanism for mTOR suppression-mediated longevity extension. It
      modestly altered gut metagenomes, and some metagenomic effects were linked to
      immune outcomes. Our data show novel mTOR inhibitor immune effects meriting
      further studies in relation to longevity and healthspan extension. 

PMID- 26315675
TI  - Comparative Risk of Hospitalized Infection Associated With Biologic Agents in
      Rheumatoid Arthritis Patients Enrolled in Medicare.
AB  - OBJECTIVE: The risks of hospitalized infection associated with biologic agents
      used to treat rheumatoid arthritis (RA) are unclear. The aim of this study was to
      determine whether the associated risk of hospitalized infections differed between
      specific biologic agents used to treat RA. METHODS: In a retrospective cohort
      study using Medicare data from 2006-2011 for all enrolled patients with RA, new
      episodes of treatment with etanercept, adalimumab, certolizumab, golimumab,
      infliximab, abatacept, rituximab, and tocilizumab were identified. Patients were
      required to have received another biologic agent previously and to have been
      continuously enrolled in Medicare medical and pharmacy plans during the baseline
      period and throughout followup. Followup started on the date of initiation of
      treatment with the new biologic agent (after previous treatment with a different
      biologic agent) and ended on the date of the earliest hospitalized infection, at
      12 months, after an exposure gap of >30 days, or at the time of death or loss of
      Medicare coverage. Cox regression analysis was used to calculate the adjusted
      hazard ratio (HR) for hospitalized infection, adjusting for an infection risk
      score and other confounders. RESULTS: Of 31,801 new biologic treatment episodes
      in patients who had previously received another biologic agent, 12.0% were with
      etanercept, 15.2% with adalimumab, 5.9% with certolizumab, 4.4% with golimumab,
      12.4% with infliximab, 28.9% with abatacept, 14.8% with rituximab, and 6.3% with
      tocilizumab. During followup, we identified 2,530 hospitalized infections;
      incidence rates ranged from 13.1 per 100 person-years (abatacept) to 18.7 per 100
      person-years (rituximab). After adjustment, etanercept (HR 1.24, 95% confidence
      interval [95% CI] 1.07-1.45), infliximab (HR 1.39, 95% CI 1.21-1.60), and
      rituximab (HR 1.36, 95% CI 1.21-1.53) had significantly higher HRs for
      hospitalized infection compared with abatacept. CONCLUSION: In RA patients with
      prior exposure to a biologic agent, exposure to etanercept, infliximab, or
      rituximab was associated with a greater 1-year risk of hospitalized infection
      compared with the risk associated with exposure to abatacept.

PMID- 26315676
TI  - The anthelmintic drug mebendazole inhibits growth, migration and invasion in
      gastric cancer cell model.
AB  - The present study aimed to investigate the effects of MBZ on a human malignant
      ascites cell line derived from a primary gastric cancer tumor. Our data reveal
      that MBZ showed high cytotoxicity in vitro, displaying an IC50 of 0.39 MUM and
      1.25 MUM in ACP-02 and ACP-03, respectively. The association between MBZ and 5-FU
      increased slightly the cytotoxicity when compared to MBZ and 5-FU alone.
      Furthermore, MBZ disrupted the microtubule structure of AGP-01 cells and
      inhibited significantly the invasion and migration of these cells. Activity of
      active MMP-2 significantly decreased at all tested concentration of MBZ compared
      to negative control. These results support the indication of MBZ in combination
      with chemotherapeutic agents as a possible adjuvant therapy for the
      management/treatment of patients with advanced gastric cancer since MBZ is a drug
      of low cost with acceptable safety profile and reduced toxicity to normal cells.
      However, clinical trials must be performed in o to evaluate its efficacy in
      gastric cancer patients.

PMID- 26315677
TI  - Immobilization of a Molecular Ruthenium Catalyst on Hematite Nanorod Arrays for
      Water Oxidation with Stable Photocurrent.
AB  - Photoelectrochemical (PEC) cells for light-driven water splitting are prepared
      using hematite nanorod arrays on conductive glass as the photoanode. These
      devices improve the photocurrent of the hematite-based photoanode for water
      splitting, owing to fewer surface traps and decreased electron recombination
      resulting from the one-dimensional structure. By employing a molecular ruthenium
      co-catalyst, which contains a strong 2,6-pyridine-dicarboxylic acid anchoring
      group at the hematite photoanode, the photocurrent of the PEC cell is enhanced
      with high stability for over 10 000 s in a 1 m KOH solution. This approach can
      pave a route for combining one-dimensional nanomaterials and molecular catalysts
      to split water with high efficiency and stability. 

PMID- 26315679
TI  - Infrared spectra reveal box-like structures for a pentamer and hexamer of mixed
      carbon dioxide-acetylene clusters.
AB  - Except for a few cases like water and carbon dioxide, identification and
      structural characterization of clusters with more than four monomers is rare.
      Here, we provide experimental and theoretical evidence for existence of box-like
      structures for a pentamer and a hexamer of mixed carbon dioxide-acetylene
      clusters. Two mid-infrared cluster absorption bands are observed in the CO2nu3
      band region using a tunable diode laser to probe a pulsed supersonic jet. Each
      requires the presence of both carbon dioxide and acetylene in the jet, and (from
      observed rotational spacings) involves clusters containing about 4 to 7
      molecules. Structures are predicted for mixed CO2 + C2H2 clusters using a
      distributed multipole model, and the bands are assigned to a specific pentamer,
      (CO2)3-(C2H2)2, and hexamer, (CO2)4-(C2H2)2. The hexamer has a box-like structure
      whose D2d symmetry is supported by observed intensity alternation in the
      spectrum. The pentamer has a closely related structure which is obtained by
      removing one CO2 molecule from the hexamer. These are among the largest mixed
      molecular clusters to be assigned by high-resolution spectroscopy. 

PMID- 26315678
TI  - Monospecific anti-Ro52/TRIM21 antibodies in a tri-nation cohort of 1574 systemic
      sclerosis subjects: evidence of an association with interstitial lung disease and
      worse survival.
AB  - OBJECTIVES: Autoantibodies directed against Ro52/TRIM21 are common in systemic
      sclerosis (SSc) but their clinical significance remains uncertain. The aim of
      this study was to assess the clinical correlates and survival of subjects with
      monospecific anti-Ro52/TRIM21 antibodies, i.e. anti-Ro52/TRIM21 antibodies in the
      absence of other SSc-related antibodies. METHODS: A tri-nation (Canada,
      Australia, USA) cohort of 1574 SSc subjects was formed, demographic and clinical
      variables were harmonised and sera were tested using a common diagnostic
      platform. Statistical analyses were performed to determine associations between
      the presence of monospecific anti-Ro52/TRIM21 antibodies and outcomes of
      interest, including interstitial lung disease (ILD) and survival. RESULTS: 103
      (6.5%) had monospecific anti-Ro52/TRIM21 antibodies, 324 (20.6%) had anti
      Ro52/TRIM21 antibodies overlapping with other SSc-related antibodies and 1147
      (72.9%) were negative for anti-Ro52/TRIM21 antibodies. Monospecific subjects were
      less likely to be White compared to negative subjects (68% vs. 82%, odds ratio
      (OR) 0.48, 95% confidence interval (CI) 0.30-0.75, p=0.0011). ILD was the only
      clinical variable significantly associated with monospecific anti-Ro52/TRIM21
      antibodies compared to negative subjects (adjusted OR 2.70, 95% CI 1.75-4.14,
      p<0.0001). Subjects with monospecific anti-Ro52/TRIM21 antibodies were at
      significantly increased risk of death compared to subjects without anti
      Ro52/TRIM21 antibodies (log rank p=0.0003; adjusted hazard ratio (HR) 1.87, 95%
      CI 1.24-2.82, p=0.0029). CONCLUSIONS: The results obtained from this unique tri
      nation cohort represent the strongest evidence to date that anti-Ro52/TRIM21
      antibodies are independently associated with the presence of ILD and poor
      survival in SSc. These data provide strong support for the predictive and
      prognostic value of this serological biomarker in SSc.

PMID- 26315680
TI  - A Strategy to Control the Reactivation of Frustrated Lewis Pairs from Shelf
      Stable Carbene Borane Complexes.
AB  - N-Phosphine oxide substituted imidazolylidenes (PoxIms) have been synthesized and
      fully characterized. These species can undergo significant changes to the spatial
      environment surrounding their carbene center through rotation of the phosphine
      oxide moiety. Either classical Lewis adducts (CLAs) or frustrated Lewis pairs
      (FLPs) are thus formed with B(C6 F5 )3 depending on the orientation of the
      phosphine oxide group. A strategy to reactivate FLPs from CLAs by exploiting
      molecular motions that are responsive to external stimuli has therefore been
      developed. The reactivation conditions were successfully controlled by tuning the
      strain in the PoxIm-B(C6 F5 )3 complexes so that reactivation only occurred above
      ambient temperature. 

PMID- 26315681
TI  - Dating concerns among women with breast cancer or with genetic breast cancer
      susceptibility: a review and meta-synthesis.
AB  - OBJECTIVE: While dating is critical in the formation of a lifelong romantic
      relationship, women with breast cancer or a genetic susceptibility to developing
      this disease report a myriad of dating concerns. This review synthesises and
      discusses the perceived dating barriers and concerns in this population. METHOD:
      A systematic search of CINAHL, Embase, MEDLINE, PsycINFO and PubMed was
      undertaken and yielded 19 published qualitative studies. Papers were subjected to
      critical appraisal to ensure the integrity of findings. RESULTS: Six areas of
      concern were identified: Feeling unattractive due to treatment side effects;
      perceiving limited dating partners available; determining how, when and what to
      disclose; fear of cancer recurrence and reduced life expectancy; apprehension
      about entering into a new sexual relationship; and dating urgency and not wanting
      to 'waste time' on partners without long-term potential. CONCLUSIONS: This paper
      provides a valuable synthesis of the complex issues, concerns and decisions that
      single women face at different stages of relationship formation following their
      breast cancer experience. Future research is warranted to explore the
      perceptions, appraisals and beliefs underlying these concerns, to help guide the
      future design and development of appropriate informational and supportive care
      offered to breast cancer patients.

PMID- 26315682
TI  - Systolic ShMOLLI myocardial T1-mapping for improved robustness to partial-volume
      effects and applications in tachyarrhythmias.
AB  - BACKGROUND: T1-mapping using the Shortened Modified Look-Locker Inversion
      Recovery (ShMOLLI) technique enables non-invasive assessment of important
      myocardial tissue characteristics. However, tachyarrhythmia may cause
      mistriggering and inaccurate T1 estimation. We set out to test whether systolic
      T1-mapping might overcome this, and whether T1 values or data quality would be
      significantly different compared to conventional diastolic T1-mapping. METHODS:
      Native T1 maps were acquired using ShMOLLI at 1.5 T (Magnetom Avanto, Siemens
      Healthcare) in 10 healthy volunteers (5 male) in sinus rhythm, at varying
      prescribed trigger delay (TD) times: 0, 50, 100 and 150 ms (all "systolic"), 340
      ms (MOLLI TD 500 ms, the conventional TD for ShMOLLI) and also "end diastolic".
      T1 maps were also acquired using a shorter readout, to explore the effect of
      reducing image readout time and sensitivity to systolic motion. The feasibility
      and image quality of systolic T1-mapping was tested in 15 patients with
      tachyarrhythmia (n = 13 atrial fibrillation, n = 2 sinus tachycardia; mean HR
      range 93-121 bpm). RESULTS: In healthy volunteers, systolic readout increased the
      thickness of myocardium compared to the diastolic readout. There was a small
      overall effect of TD on T1 values (p = 0.04), with slightly shorter T1 values in
      systole compared to diastole (maximum difference 10 ms). While there were
      apparent gender differences (with no effect of TD on T1 values in males, more
      marked differences in females, and exaggeration of this effect in thinner
      myocardial segments in females), dilatation and erosion of contours suggested
      that the effect of TD on T1 in females was almost entirely due to more partial
      volume effects in diastole. All T1 maps were of excellent quality, but systolic
      TD and shorter readout were associated with less variability in segmental T1
      values. In tachycardic patients, systolic acquisitions produced consistently
      excellent T1 maps (median R (2) = 0.993). CONCLUSIONS: In healthy volunteers,
      systolic ShMOLLI T1-mapping reduces T1 variability and reports clinically
      equivalent T1 values to conventional diastolic readout; slightly shorter T1
      values in systole are mostly explained by reduced partial-volume effects due to
      the increase in functional myocardial thickness. In patients with
      tachyarrhythmia, systolic ShMOLLI T1-mapping is feasible, circumvents
      mistriggering and produces excellent quality T1 maps. This extends its clinical
      applicability to challenging rhythms (such as rapid atrial fibrillation) and aids
      the investigation of thinner myocardial segments. With further validation,
      systolic T1-mapping may become a new and convenient standard for myocardial T1
      mapping.

PMID- 26315683
TI  - Associations of spontaneous self-affirmation with health care experiences and
      health information seeking in a national survey of US adults.
AB  - OBJECTIVE: Self-affirming--such as by reflecting on one's strengths and values-
      reduces defensiveness to threatening information, reduces negative effects of
      stereotype threat and promotes prosociality. These outcomes may promote physical
      health, highlighting a need to examine the role of self-affirmation in medical
      and health contexts. DESIGN: Data were collected as part of the nationally
      representative, cross-sectional, 2013 Health Information National Trends Survey.
      Items were completed by 2731 respondents. MAIN OUTCOME MEASURES: Respondents
      answered questions about spontaneous self-affirmation tendencies, perceptions of
      providers and health care, involvement in medical appointments, health
      information seeking and engagement in medical research. RESULTS: Spontaneous self
      affirmation was associated with more positive perceptions of communication with
      one's provider, better perceived quality of care, greater likelihood of asking
      questions in a medical appointment, greater information seeking for oneself and
      multiple indices of surrogate information seeking (i.e. seeking information for
      others). Four of eight significant associations remained significant when
      controlling for optimism. The associations of self-affirmation with aspects of
      the patient-provider relationship were not modified by factors likely to be
      associated with stereotype threat (e.g. race or BMI). CONCLUSION: Spontaneous
      self-affirmation was related to positive outcomes in health contexts.
      Experimental research is needed to further explore the causal nature of these
      associations.

PMID- 26315684
TI  - Evaluation of Cytochrome P450 (CYP) 3A4-Based Interactions of Levomilnacipran
      with Ketoconazole, Carbamazepine or Alprazolam in Healthy Subjects.
AB  - BACKGROUND AND OBJECTIVES: Levomilnacipran is a serotonin and norepinephrine
      reuptake inhibitor with balanced potency for the reuptake inhibition of
      norepinephrine and serotonin, approved in the USA for the treatment of major
      depressive disorder (MDD) in adults. We conducted studies in healthy human
      subjects to investigate pharmacokinetic interactions when levomilnacipran
      extended-release (ER) is administered in combination with an inhibitor
      (ketoconazole), an inducer (carbamazepine), or a substrate (alprazolam) of
      cytochrome P450 (CYP) 3A4. METHODS: Randomised, open-label studies were conducted
      in healthy volunteers (n = 34 ketoconazole, n = 34 carbamazepine, n = 30
      alprazolam) and pharmacokinetic parameters were determined when levomilnacipran
      was administered alone or together with the relevant study drug. RESULTS: Co
      administration of ketoconazole with levomilnacipran ER increased levomilnacipran
      maximum concentration (C max) by 39% [90% confidence interval (CI) 31-47%] and
      area under the concentration-time curve (AUC) by 57% (90% CI 47-67%), whereas
      carbamazepine reduced the C max and AUC of levomilnacipran by 26% (90% CI 22-30%)
      and 29% (90% CI 26-32%), respectively. Levomilnacipran at steady state had no
      significant effect on the pharmacokinetics of a single 1 mg dose of alprazolam
      extended release (XR); neither did single-dose alprazolam XR affect the steady
      state pharmacokinetics of levomilnacipran. No new safety concerns were noted in
      these studies. CONCLUSIONS: Based on these results, the levomilnacipran ER dose
      should not exceed 80 mg once daily when used with ketoconazole, compared to 120
      mg once daily in the absence of ketoconazole. No dose adjustment for
      levomilnacipran is suggested when levomilnacipran ER is co-administered with
      carbamazepine or other CYP3A4 inducers. Co-administration with levomilnacipran of
      drugs metabolised by CYP3A4, such as alprazolam, requires no dose adjustment due
      to pharmacokinetic considerations.

PMID- 26315685
TI  - Lithium-Associated Hyperparathyroidism: A Pooled Analysis.
AB  - BACKGROUND: Lithium treatment has been associated with hyperparathyroidism (HPT).
      However, there are conflicting data regarding the rate of single- (SGD) versus
      multiple-gland disease (MGD) as well as the optimum surgical approach in these
      cases. METHODS: Published data were identified through systematic electronic
      literature searches. Studies that fulfilled the preset inclusion criteria were
      analyzed (n = 12). RESULTS: These studies documented 210 lithium-associated HPT
      (LAH) cases. Of these, 103 (49%) were due to SGD and 107 (51%) due to MGD. The
      unadjusted odds ratio of having multiple LAH compared to sporadic HPT was 3.44
      (95% confidence interval 2.5907-4.5633; p < 0.0001). The sensitivity of
      preoperative sestamibi and sonography for SGD was 66-100 and 75-82%,
      respectively. The sensitivity for MGD was 9-67% for both. Intraoperative
      parathyroid hormone monitoring was utilized in 6 studies. Three studies
      recommended minimally invasive parathyroidectomy (MIP), while the other 3
      recommended bilateral exploration. CONCLUSION: LAH is a relatively frequent
      condition among patients on lithium, and calcium monitoring should be performed
      initially and longitudinally. Almost half of the LAH cases are due to SGD. MIP
      should be the optimum surgical approach.

PMID- 26315686
TI  - Adaptive mutations in PB2 gene contribute to the high virulence of a natural
      reassortant H5N2 avian influenza virus in mice.
AB  - The highly pathogenic A/chicken/Hebei/1102/2010 (HB10) H5N2 virus is a natural
      reassortant derived from circulating H5N1 and endemic H9N2 avian influenza
      viruses (AIV). To evaluate the potential of its interspecies transmission, we
      previously serially passaged the non-virulent HB10 virus in the mouse lung and
      obtained a high virulence variant (HB10-MA). Genomic sequencing revealed five
      mutations (HA-S227N, PB2-Q591K, PB2-D701N, PA-I554V and NP-R351K) that
      distinguished HB10-MA virus from its parental HB10 virus. In this study, we
      further investigated the molecular basis for the enhanced virulence of HB10-MA in
      mice. By generating a series of reassortants between the two viruses and
      evaluating their virulence in mice, we found that both PB2 and PA genes
      contribute to the high virulence of HB10-MA in mice, whereas PB2 gene carrying
      the 591K and/or 701N had a dominant function. In addition, the two amino acids
      showed a cumulative effect on the virulence, virus replication, and polymerase
      activity of HB10 or HB10-MA. Therefore, our results collectively emphasized the
      crucial role of PB2 gene, particularly the paired mutations of Q591K and D701N in
      the host adaptation of the novel reassortant H5N2 AIV in mammals, which may
      provide helpful insights into the pathogenic potential of emerging AIV in human
      beings. 

PMID- 26315687
TI  - Hirame rhabdovirus (HIRRV) as the cause of a natural disease outbreak in cultured
      black seabream (Acanthopagrus schlegeli) in Korea.
AB  - In 2015, a high mortality rate of about 40% was observed in black seabream
      (Acanthopagrus schlegeli) on a farm on the southern coast of Korea. Most of the
      diseased fish showed a hemorrhage of the mouth, pale liver, petechial
      hemorrhaging in the internal fat, and an enlarged spleen. Other than Alella sp.,
      no parasites or bacteria were isolated from the diseased fish, and all of the
      tissue filtrates produced cytopathic effects (CPEs) in FHM and CHSE-214 cells. A
      polymerase chain reaction analysis revealed that the cell culture supernatants
      with CPE expressed specific 730-bp fragments for the hirame rhabdovirus (HIRRV)
      phosphoprotein gene. The nucleotide sequences showed a minimum of 95.8% identity
      to five other known isolates of HIRRV, including CA-9703 and 8401-H from olive
      flounder (Paralichthys olivaceus) in Korea and Japan. An experimental challenge
      was conducted in which the virus was delivered by injection, and the cumulative
      mortalities of black seabream challenged with this new HIRRV isolate at 10(4.8)
      TCID50/fish and 10(3.8) TCID50/fish were 100% and 20%, respectively. This
      fulfilled Koch's postulates and confirmed that HIRRV was the cause of disease and
      mortality for both the natural and experimental infection of black seabream.

PMID- 26315688
TI  - Antiviral effect of lithium chloride on infection of cells by canine parvovirus.
AB  - Canine parvovirus type 2 causes significant viral disease in dogs, with high
      morbidity, high infectivity, and high mortality. Lithium chloride is a potential
      antiviral drug for viruses. We determined the antiviral effect of Lithium
      Chloride on canine parvovirus type 2 in feline kidney cells. The viral DNA and
      proteins of canine parvovirus were suppressed in a dose-dependent manner by
      lithium chloride. Further investigation verified that viral entry into cells was
      inhibited in a dose-dependent manner by lithium chloride. These results indicated
      that lithium chloride could be a potential antiviral drug for curing dogs with
      canine parvovirus infection. The specific steps of canine parvovirus entry into
      cells that are affected by lithium chloride and its antiviral effect in vivo
      should be explored in future studies. 

PMID- 26315689
TI  - Aging Effects on Whole-Brain Functional Connectivity in Adults Free of Cognitive
      and Psychiatric Disorders.
AB  - Aging is associated with decreased resting-state functional connectivity (RSFC)
      within the default mode network (DMN), but most functional imaging studies have
      restricted the analysis to specific brain regions or networks, a strategy not
      appropriate to describe system-wide changes. Moreover, few investigations have
      employed operational psychiatric interviewing procedures to select participants;
      this is an important limitation since mental disorders are prevalent and
      underdiagnosed and can be associated with RSFC abnormalities. In this study,
      resting-state fMRI was acquired from 59 adults free of cognitive and psychiatric
      disorders according to standardized criteria and based on extensive
      neuropsychological and clinical assessments. We tested for associations between
      age and whole-brain RSFC using Partial Least Squares, a multivariate technique.
      We found that normal aging is not only characterized by decreased RSFC within the
      DMN but also by ubiquitous increases in internetwork positive correlations and
      focal internetwork losses of anticorrelations (involving mainly connections
      between the DMN and the attentional networks). Our results reinforce the notion
      that the aging brain undergoes a dedifferentiation processes with loss of
      functional diversity. These findings advance the characterization of healthy
      aging effects on RSFC and highlight the importance of adopting a broad, system
      wide perspective to analyze brain connectivity.

PMID- 26315690
TI  - Effects of a Neonatal Experience Involving Reward Through Maternal Contact on the
      Noradrenergic System of the Rat Prefrontal Cortex.
AB  - The noradrenergic system plays an important role in prefrontal cortex (PFC)
      function. Since early life experiences play a crucial role in programming brain
      function, we investigated the effects of a neonatal experience involving reward
      through maternal contact on the noradrenergic system of the rat PFC. Rat pups
      were exposed during Postnatal days (PNDs) 10-13, to a T-maze in which contact
      with the mother was used as a reward (RER). RER males had higher norepinephrine
      levels in the PFC both on PND 13 and in adulthood. The RER experience resulted in
      adulthood in increased levels of the active demethylase GADD45b, hypomethylation
      of the beta1 adrenergic receptor (ADRB1) gene promoter, and consequent enhanced
      expression of its mRNA in the PFC. In addition, protein and binding levels of the
      ADRB1, as well as those of its downstream effector phosphorylated cAMP response
      element-binding protein were elevated in RER males. The higher activity of the
      PFC noradrenergic system of the RER males was reflected in their superior
      performance in the olfactory discrimination and the contextual fear extinction, 2
      PFC noradrenergic system-dependent behavioral tasks.

PMID- 26315691
TI  - Changing sources of polychlorinated dibenzo-p-dioxins and furans in sediments and
      ecological risk for nekton in the lower Passaic River and Newark Bay, New Jersey,
      USA.
AB  - Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) were measured in
      sediments (surface and deeper sediments) and porewater of the lower Passaic River
      and Newark Bay (New Jersey, USA) to apportion their sources and conduct an
      ecological risk assessment. Positive matrix factorization was applied to identify
      sources of PCDD/Fs. Five source profiles were extracted from the positive matrix
      factorization model applied to the sediment samples including chloranil,
      combustion, polychlorinated biphenyl impurities, mixed urban sources, and the
      historical contamination from the former Diamond Alkali plant. The ecological
      risk assessment was estimated using several lines of evidence depending on site
      specific data (blue crab and fish samples representing different feeding habits
      and positions in the trophic wood web of the river). Porewater concentrations
      gave the best estimates of lipid concentrations especially in the blue crab
      samples (with an average factor difference of 3.8). Calculated hazard quotients
      (HQs) for the fish samples and blue crab were >1 based on the no-effect
      concentration and tissue screening concentration approaches. At the same time,
      calculated porewater toxic units were >1. Sediment concentrations exceeded the
      published sediment quality guidelines for the protection of fish and benthic
      species, indicating the existence of significant risk to the aquatic life in the
      Passaic River. Accordingly, further actions and control measures are needed to
      reduce the emission of PCDD/Fs from ongoing sources.

PMID- 26315693
TI  - A comparison of rheumatoid arthritis and systemic lupus erythematosus trial
      design: a commentary on ways to improve the number of positive trials in SLE.
AB  - OBJECTIVES: Recent systemic lupus erythematosus (SLE) randomised controlled
      trials (RCTs) were examined for potential design flaws and compared to rheumatoid
      arthritis (RA) RCT over the same time period to suggest modifications to SLE RCTs
      that could help improve the potential success rate of future SLE trials. METHODS:
      RA and SLE biologics RCTs published between 2005 and July 2013 were identified
      using PubMed. Inclusion criteria, study design, outcome measures, sample size
      calculations, patient baseline characteristics steroid use in the protocol and
      results were extracted and compared. RESULTS: All trials required active disease
      for enrolment. Twenty-two RA RCTs and eight SLE RCTs were included. All RA RCTs
      used either a partial or continuous measure of improvement. SLE RCTs used SLEDAI,
      BILAG, SLAM, SRI and BICLA. RA trials were larger (543 vs. 376 participants).
      Concomitant corticosteroid use was stable in 100% of RA trials while all SLE RCTs
      allowed dose tapering. RA trials were mostly in methotrexate or DMARD inadequate
      responders whereas SLE trials allowed for the presence or absence
      immunosuppressives within all trials. Sample sizes in RA were determined on a
      change in disease activity or proportion meeting a disease state. Positive trials
      were found in 100% of RA RCTs and 25% of SLE RCTs. CONCLUSIONS: The potential
      insensitivity of SLE disease activity indices to partial improvements may result
      in type II errors in SLE RCTs. Varying concomitant pharmacotherapy, especially
      corticosteroid use, in SLE may blunt observed treatment effects. Steroid tapering
      should be considered a trial outcome in isolation. More realistic sample size
      calculations are needed in SLE.

PMID- 26315692
TI  - Mental health outcomes during colorectal cancer survivorship: a review of the
      literature.
AB  - OBJECTIVE: This article reviews literature on adults' mental health outcomes
      during acute and long-term colorectal cancer (CRC) survivorship. METHODS: We
      identified articles that included at least one measure of psychological symptoms
      or mental quality of life or well-being through a search of databases (CINAHL,
      MEDLINE, PsycINFO, and PsycARTICLES). Articles were published between January
      2004 and April 2015. RESULTS: A significant proportion of CRC survivors
      experience clinically meaningful levels of anxiety and depressive symptoms or
      reduced mental well-being across the trajectory of the illness. Demographic,
      medical, and psychosocial predictors of mental health outcomes were identified.
      However, few studies were theory-driven, and gaps remain in our understanding of
      risk and protective factors with respect to mental health outcomes, especially
      during long-term CRC survivorship. CONCLUSIONS: Theory-driven longitudinal
      research with larger samples is required to identify subgroups of CRC survivors
      with different trajectories of psychological adjustment. Such research would
      assess adjustment as a function of internal resources (e.g., personality and
      coping) and external resources (e.g., finances and social support) to inform
      future interventions for CRC survivors. Copyright (c) 2015 John Wiley & Sons,
      Ltd.

PMID- 26315695
TI  - Pre-hospital management of patients with chest pain and/or dyspnoea of cardiac
      origin. A position paper of the Acute Cardiovascular Care Association (ACCA) of
      the ESC.
AB  - Chest pain and acute dyspnoea are frequent causes of emergency medical services
      activation. The pre-hospital management of these conditions is heterogeneous
      across different regions of the world and Europe, as a consequence of the variety
      of emergency medical services and absence of specific practical guidelines. This
      position paper focuses on the practical aspects of the pre-hospital treatment on
      board and transfer of patients taken in charge by emergency medical services for
      chest pain and dyspnoea of suspected cardiac aetiology after the initial
      assessment and diagnostic work-up. The objective of the paper is to provide
      guidance, based on evidence, where available, or on experts' opinions, for all
      emergency medical services' health providers involved in the pre-hospital
      management of acute cardiovascular care.

PMID- 26315694
TI  - The emergence of sedentary behaviour physiology and its effects on the
      cardiometabolic profile in young and older adults.
AB  - It has recently emerged that sedentary behaviour is independent of a lack of
      physical activity as individuals can be sufficiently active, based on the
      recommended physical activity guidelines, but also spend the majority of their
      waking hours engaging in sedentary behaviour. Individuals who follow this pattern
      of physical activity and sedentary behaviour are known as 'active couch
      potatoes'. Sedentary behaviour has been found to have detrimental effects on
      cardiometabolic markers associated with cardiovascular disease. Since the
      positive effects of moderate-to-vigorous intensity physical activity do not
      necessarily negate the deleterious effects of sedentary behaviour on
      cardiometabolic markers, it is postulated that engaging in light physical
      activity is an intervention that will successfully reduce levels of sedentary
      behaviour and may hence improve health markers of quality of life. We propose
      that such lifestyle changes may be particularly relevant to older populations as
      these engage in sedentary behaviour for the majority of their waking hours,
      thereby adding to the negative aging effect on cardiometabolic markers. 

PMID- 26315696
TI  - Mixed-Metal Coordination Cages Constructed with Pyridyl-Functionalized beta
      Diketonate Metalloligands: Syntheses, Structures and Host-Guest Properties.
AB  - The design and synthesis of mixed-metal coordination cages, which can act as
      hosts to encapsule guest molecules, is a subject of intensive research, and the
      utilization of metalloligand is an effective method to construct a designed
      heterometallic architecture. Herein, a series of heterometallic cages with half
      sandwich Rh, Ir and Ru fragments using Cu(II) -metalloligand as a building block
      by a stepwise approach is reported. The cavity sizes of the cages could be
      controlled easily by the lengths of the organic ligands. Because the
      metalloligands in the oxalate-based cage are somewhat distorted and concave,
      there are weak Cu???O interactions in the molecules, forming a binuclear copper
      unit. By increasing the height of the cages using longer ligands, 2,5-dichloro
      3,6-dihydroxy-1,4-benzoquinone (H2 CA), the organometallic boxes display
      interesting host-guest behavior, which are made large enough to accommodate some
      large molecules, such as pyrene and [Pt(acac)2 ]. Interestingly, the
      heterometallic cage with larger cavity size can transfer into a homometallic
      hexanuclear prism in the presence of pyrazine. 

PMID- 26315697
TI  - The Appearance of a Leptin Effect on Glucose Absorption in Caco2 Cells Depends on
      Their Differentiation Level.
AB  - Backdround/Aims: The aim of this work was to study the effect and mechanism of
      action of leptin added apically, on glucose absorption, using Caco-2 cells as a
      model. METHODS: Cells were grown on inserts and treated with leptin, at different
      time points after confluence. Radiolabelled glucose was added to the upper
      chamber and samples from the lower chamber were collected and assayed for
      radioactivity. RESULTS: Glucose absorption increased with an increase in the
      level of differentiation and was associated with an increase in the protein
      expression level of glucose transporters. Leptin reduced glucose absorption only
      by day 16 after confluence, the time at which apical leptin receptors started
      appearing. This inhibitory effect became higher the longer the post confluence
      period, and was prominent on day 23. The hormone effect was found to be mediated
      via a decrease in the number of glucose transporters (SGLT1 and GLUT2) and a
      decrease in the activity of the Na+/K+ ATPase which was assayed by measuring the
      amount of inorganic phosphate liberated in presence and absence of enzyme
      activators. CONCLUSION: It was concluded that by day 23 post confluence, Caco-2
      cells are differentiated and are appropriate to use as a model for intestinal
      transport studies.

PMID- 26315698
TI  - Reply to 'Results of conservative management for consecutive esotropia after
      intermittent exotropia surgery'.

PMID- 26315699
TI  - Prior rates of visual field loss and lifetime risk of blindness in glaucomatous
      patients undergoing trabeculectomy.
AB  - PURPOSE: Trend-based analyses examining rates of visual field (VF) loss in
      glaucoma are useful for predicting risk of vision-related morbidity. Although
      patients with faster losses are likely to require treatment escalation, little is
      known about rates that might trigger a decision to intervene surgically. The aims
      of this study were to investigate prior rates of VF loss in patients attending
      for trabeculectomy and to estimate, in the absence of surgical intervention,
      lifetime risk of visual impairment, and blindness. PATIENTS AND METHODS: A
      retrospective analysis of 117 eyes of 86 consecutive patients with glaucoma
      attending for trabeculectomy, including 53 patients referred from general
      ophthalmology clinics and 33 patients from specialist glaucoma clinics. Rates of
      change in standard automated perimetry mean deviation were examined using linear
      regression and random coefficient models. Risk of lifetime visual impairment and
      blindness was calculated using life expectancy data. RESULTS: Mean age at surgery
      was 71.0+/-9.7 years. Patients were followed for 10.7+/-7.5 years prior to
      surgery with an average of seven useable fields per eye. On average patients
      referred from general clinics lost 1.04 dB/year compared with 0.77 dB/year in
      those referred from glaucoma clinics (P=0.070). Patients referred from general
      clinics had more medication changes prior to surgery (3.4 and 2.6 changes,
      respectively; P=0.004). Given Scottish life expectancy data, untreated, 61 eyes
      (52%) would have passed the threshold for visual impairment, whereas 40 (34%)
      would have passed the threshold demarcating blindness. CONCLUSION: Patients
      attending for trabeculectomy had faster average rates of field loss prior to
      surgery than published values for the general glaucoma population with over one
      third of eyes studied predicted to have become blind without intervention. Those
      managed by glaucoma specialists had fewer changes in medication and tended to
      slower rates of VF loss, although the latter did not reach statistical
      significance.

PMID- 26315701
TI  - Are rates of vision loss in patients in English glaucoma clinics slowing down
      over time? Trends from a decade of data.
AB  - PURPOSE: To examine changes in rates of visual field (VF) progression in patients
      attending a sample of glaucoma clinics in England between 1999 and 2012. METHODS:
      An archive of 473 252 Humphrey VFs recorded across the UK was retrospectively
      examined. Distribution of rates recorded in the first half of the decade was
      compared with the second. The relationship between age and severity of MD loss at
      baseline with rates of loss and frequency of testing was examined. RESULTS: VF
      series from 18 926 eyes were analysed. Median rate of MD loss for the period
      before and after 2003 was -0.11 and -0.06 dB/year, respectively, but the
      proportion of eyes with medium or fast rates of MD loss remained constant. Median
      rate of MD loss in older (>70 years) eyes was faster than that observed in
      younger (<60 years) eyes (-0.21 compared with -0.01 dB/year). Median rate of loss
      did not vary with severity of MD loss at baseline. Frequency of testing,
      typically carried out annually, did not vary by age, rate of loss or disease
      severity. CONCLUSIONS: VFs of eyes treated in the first half of the decade
      deteriorated more rapidly than those in the second half. Several factors might
      explain these differences but average effects were small and there was no
      reduction in the proportion of rapidly progressing eyes over the decade. Older
      age and, to a lesser extent, worse VF damage at diagnosis are indicators for
      faster VF loss in clinics, but frequency of VF testing was similar for all
      patients.

PMID- 26315700
TI  - Measures of socioeconomic status and self-reported glaucoma in the U.K. Biobank
      cohort.
AB  - PURPOSE: To determine ocular, demographic, and socioeconomic associations with
      self-reported glaucoma in the U.K. Biobank. METHODS: Biobank is a study of U.K.
      residents aged 40-69 years registered with the National Health Service. Data were
      collected on visual acuity, intraocular pressure (IOP), corneal biomechanics, and
      questionnaire from 112,690 participants. Relationships between ocular,
      demographic, and socioeconomic variables with reported diagnosis of glaucoma were
      examined. RESULTS: In all, 1916 (1.7%) people in U.K. Biobank reported glaucoma
      diagnosis. Participants reporting glaucoma were more likely to be older (mean
      61.4 vs. 56.7 years, P<0.001) and male (2.1% vs. 1.4%, P=0.001). The rate of
      reported glaucoma was significantly higher in Black (3.28%, P<0.001) and Asian
      (2.14%, P=0.009) participants compared with White participants (1.62%,
      reference). Cases of reported glaucoma had a higher mean IOP (18 mm Hg both eyes,
      P<0.001), lower corneal hysteresis (9.96 right eye, 9.89 left eye, P<0.001), and
      lower visual acuity (0.09 logMAR right eye, 0.08 logMAR left eye, P<0.001)
      compared with those without (16 mm Hg both eyes, hysteresis 10.67 right eye,
      10.63 left eye, 0.03 logMAR right eye, 0.02 logMAR left eye). The mean Townsend
      deprivation index was -0.72 for those reporting glaucoma and -0.95 for those
      without (P<0.001), indicating greater relative deprivation in those reporting
      glaucoma. Multivariable logistic regression showed that people in the lowest
      income group (<L18,000/year) were significantly more likely to report a diagnosis
      of glaucoma compared with any other income level (P<0.01). We observed increasing
      glaucoma risk across the full range of income categories, with highest risk among
      those of lowest income, and no evidence of a threshold effect. CONCLUSIONS: In a
      large U.K. cohort, individuals reporting glaucoma had more adverse socioeconomic
      characteristics. Study of the mechanisms explaining these effects may aid our
      understanding of health inequality and will help inform public health
      interventions.

PMID- 26315702
TI  - Is day-1 postoperative review necessary after pars plana vitrectomy?
AB  - PURPOSE: This study aimed to determine the proportion of patients requiring
      alteration in management based on the findings of the day-1 postoperative visit
      after pars plana vitrectomy, and to identify clinical characteristics that
      predict the need for unexpected intervention. PATIENTS AND METHODS: A
      retrospective case note review was conducted of all patients who underwent pars
      plana vitrectomy and who then attended for review on the first postoperative day.
      All patients received routine prophylactic anti-glaucoma medication. RESULTS: Two
      hundred and seventy-three patients examined on day 1 following vitrectomy were
      studied. Indications for surgery included retinal detachment, epiretinal
      membrane, macular hole, vitreous haemorrhage, diabetic eye disease, and floaters.
      Twenty-gauge (20G) vitrectomy was performed in 124 eyes (45%); 23-gauge (23G)
      vitrectomy was performed in 149 eyes (55%). Phacoemulsification was performed
      concurrently in 51/273 (19%) eyes. Ten patients (3.7%) required unexpected
      intervention on day 1 owing to intraocular pressure (IOP) >30 (2/273), IOP <6
      (5/273), or unexpected return to theatre for anterior chamber washout (3/273).
      There was no difference in intervention rate or day-1 IOP between 20G and 23G
      cases. Hypotony was less common if gas tamponade was used (chi(2)-test, P<0.001).
      Patients undergoing combined phacoemulsification and 20G vitrectomy were
      significantly more likely to require intervention on day 1 than patients
      undergoing 20G vitrectomy alone (15.0 vs 1.9%, P=0.029, Fisher's exact test) but
      this was not the case for patients undergoing 23G vitrectomy (0 vs 4.2%, Fisher's
      exact test, P=0.58). CONCLUSIONS: The intervention rate on the first day after
      vitrectomy is low and day-1 postoperative review can be safely omitted in the
      majority of patients undergoing vitrectomy.

PMID- 26315703
TI  - Results of conservative management for consecutive esotropia after intermittent
      exotropia surgery.

PMID- 26315704
TI  - Cost effectiveness of collagen crosslinking for progressive keratoconus in the UK
      NHS.
AB  - BACKGROUND: Keratoconus is a progressive degenerative corneal disorder of
      children and young adults that is traditionally managed by refractive error
      correction, with corneal transplantation reserved for the most severe cases. UVA
      collagen crosslinking is a novel procedure that aims to prevent disease
      progression, currently being considered for use in the UK NHS. We assess whether
      it might be a cost-effective alternative to standard management for patients with
      progressive keratoconus. METHODS: We constructed a Markov model in which we
      estimated disease progression from prospective follow-up studies, derived costs
      derived from the NHS National Tariff, and calculated utilities from linear
      regression models of visual acuity in the better-seeing eye. We performed
      deterministic and probabilistic sensitivity analyses to assess the impact of
      possible variations in the model parameters. RESULTS: Collagen crosslinking is
      cost effective compared with standard management at an incremental cost of L 3174
      per QALY in the base case. Deterministic sensitivity analysis shows that this
      could rise above L 33,263 per QALY if the duration of treatment efficacy is
      limited to 5 years. Other model parameters are not decision significant. Collagen
      crosslinking is cost effective in 85% of simulations at a willingness-to-pay
      threshold of L 30,000 per QALY. CONCLUSION: UVA collagen crosslinking is very
      likely to be cost effective, compared with standard management, for the treatment
      of progressive keratoconus. However, further research to explore its efficacy
      beyond 5 years is desirable.

PMID- 26315705
TI  - The Royal College of Ophthalmologists Guidelines on retinal vein occlusions:
      executive summary.

PMID- 26315707
TI  - New superior-inferior visual field asymmetry indices for detecting POAG and their
      agreement with the glaucoma hemifield test.
AB  - PURPOSE: To describe and measure the discriminatory performance of three new
      superior-inferior asymmetry indices for detecting primary open angle glaucoma
      (POAG) and to compare these with the glaucoma hemifield test (GHT). METHODS: In
      all, 412 control and 247 POAG eyes were selected from a visual field database of
      patients attending the Manchester Royal Eye Hospital. Age-adjusted defect
      asymmetries were calculated for each of the 22 vertically mirrored test point
      pairs used in the GHT. The three new indices, hemifield mean difference (HMD) and
      hemifield standard deviation (HSD) of the asymmetry values along with the number
      of test pairs (NP) falling outside the 85% probability limits of the control
      population, were calculated. ROC curves of the indices and GHT were constructed.
      Agreement between the indices was explored with a proportional Venn diagram and 3
      * 3 contingency tables. Cases of disagreement between the indices were reviewed.
      RESULTS: The area under the ROC curves were HMD=0.745 (95% confidence interval
      (CI) 0.705-0.786), HSD=0.864 (95% CI 0.833-0.894), NP=0.863 (95% CI 0.832-0.893)
      and GHT=0.792 (95% CI 0.754-0.829). The Venn diagram and contingency tables
      highlighted the good agreement between HSD, NP and GHT. Agreement was 78% (HSD
      vs. GHT) and 82% (NP vs. GHT) in the control sample and 70% (HSD vs. GHT) and 71%
      (NP vs. GHT) in the POAG sample. Five cases are presented where disagreement
      existed between the indices. CONCLUSIONS: The new HSD and NP asymmetry indices
      perform better than GHT in differentiating between normal and POAG eyes in this
      data set. GHT can fail to detect significant asymmetry, detected by HSD and NP,
      when an early defect crosses sector boundaries.

PMID- 26315708
TI  - Total Body Photography as an Aid to Skin Self-examination: A Patient's
      Perspective.
AB  - Skin self-examination can help patients who are at high risk for developing
      melanoma to become more involved in their own surveillance and treatment. This
      study examined the use of total body photography as an aid to skin self
      examination from the patients' perspective. A total of 179 individuals at high
      risk for developing melanoma who had undergone total body photography (60.5%
      response rate) completed a self-reported questionnaire assessing the frequency of
      skin self-examination, perceived usefulness of total body photography, and a
      variety of potential demographic, clinical and psychological factors. Only
      approximately half of the participants indicated skin self-examination as useful
      and 78.9% preferred clinical skin examination by a specialist. Finding total body
      photography useful was associated with having received instructions on how to
      perform skin self-examination, the use of a (hand)mirror, and confidence to
      detect changing moles. These findings allow us to develop strategies to further
      improve patients' self-screening behaviours. 

PMID- 26315706
TI  - Genes, pathways, and animal models in primary open-angle glaucoma.
AB  - Glaucoma is an optic neuropathy characterized by loss of retinal ganglion cells
      (RGCs) and consequently visual field loss. It is a complex and heterogeneous
      disease in which both environmental and genetic factors play a role. With the
      advent of genome-wide association studies (GWASs), the number of loci associated
      with primary open-angle glaucoma (POAG) have increased greatly. There has also
      been major progress in understanding the genes determining the vertical cup-disc
      ratio (VCDR), disc area (DA), cup area (CA), intraocular pressure (IOP), and
      central corneal thickness (CCT). In this review, we will update and summarize the
      genetic loci associated so far with POAG, VCDR, DA, CA, IOP, and CCT. We will
      describe the pathways revealed and supported by genetic association studies,
      integrating current knowledge from human and experimental data. Finally, we will
      discuss approaches for functional genomics and clinical translation. 

PMID- 26315710
TI  - Adiponectin in Asthma and Obesity: Protective Agent or Risk Factor for More
      Severe Disease?
AB  - PURPOSE: The relationship between asthma and obesity is well established,
      although the pathophysiological mechanisms linking both diseases remain unknown.
      Adiponectin is a hormone secreted by adipose cells, plays a role in the
      modulation of inflammation and may be the key linking these two types of
      inflammation. METHODS: We conducted a cross-sectional study with asthma with
      different body mass indices (BMI); the patients were classified as eutrophic,
      overweight, or obese. We assessed disease control using the GINA consensus, and
      the levels of adiponectin, C-reactive protein (CRP) and interleukin 33 (IL-33) in
      each of the patients. RESULTS: We evaluated 75 of the 96 patients eligible for
      the study, including 25 in each BMI group. The CRP levels were significantly
      higher in the obese patients compared with both the eutrophic (p = 0.01) and the
      overweight (p = 0.03) patients. The mean adiponectin level was 21.82 +/- 9.93
      mg/L for the eutrophic asthmatics, which is a level that was significantly higher
      than in the overweight (15.31 +/- 6.27 mg/L, p = 0.0140) and the obese (16.69 +/-
      11.45 mg/L, p = 0.0287) patients. The patients with higher adiponectin levels
      exhibited smaller FEV1 (p = 0.02) and lower FVC (p = 0.003). The IL-33 levels
      were not different between the groups. CONCLUSIONS: Adiponectin does not protect
      against the development of inflammation in the setting of asthma and may in fact
      exacerbate the disease via its anti-TH1 inflammatory effects, allowing for
      increased TH2 differentiation and a more severe allergic response.

PMID- 26315711
TI  - Once daily ledipasvir/sofosbuvir fixed-dose combination with ribavirin in
      patients with inherited bleeding disorders and hepatitis C genotype 1 infection.
AB  - AIM: People with inherited bleeding disorders have been disproportionally
      affected by HCV. We assessed the fixed-dose combination of the NS5A inhibitor
      ledipasvir (LDV) with the NS5B polymerase inhibitor sofosbuvir (SOF) with
      ribavirin (RBV) in patients with genotype 1 HCV and inherited bleeding disorders.
      METHODS: To be eligible, patients had to be over 18 years of age and have an
      inherited bleeding disorder. HCV treatment-naive and -experienced patients could
      enrol. All patients received LDV 90 mg per SOF 400 mg once daily and weight-based
      RBV in a divided dose for 12 weeks. The primary efficacy endpoint was sustained
      virologic response (SVR), defined as HCV RNA below the limit of detection (15 IU
      mL-1 ) 12 weeks after the end of treatment (SVR12). RESULTS: Of the 14 patients
      enrolled, 8 (57%) had haemophilia A, 3 (21%) had haemophilia B and 2 (14%) had
      von Willebrand disease, and 1 (7%) had factor XIII deficiency. All 14 patients
      (100%, 95% CI: 77-100%) achieved SVR12. Treatment was well tolerated: all
      patients completed therapy, with mostly mild adverse events. No specific safety
      concerns associated with the patient's underlying bleeding disorders were noted.
      CONCLUSION: These results appear to suggest that people with HCV and inherited
      bleeding disorders can be safely and effectively treated with 12 weeks of LDV/SOF
      plus RBV.

PMID- 26315712
TI  - Attitudes of physicians toward assessing risk and using granulocyte colony
      stimulating factor as primary prophylaxis in patients receiving chemotherapy
      associated with an intermediate risk of febrile neutropenia.
AB  - Febrile neutropenia (FN) is a potentially fatal complication of chemotherapy.
      This prospective, observational study describes physicians' approaches toward
      assessing FN risk in patients receiving chemotherapy regimens with an
      intermediate (10-20 %) FN risk. In the baseline investigator assessment,
      physicians selected factors considered important when assessing overall FN risk
      and deciding on granulocyte colony-stimulating factor (G-CSF) primary prophylaxis
      (PP). Physicians then completed patient assessments using the same lists of
      factors. The final FN risk scores and whether G-CSF PP was planned were reported.
      The final analysis included 165 physicians and 944 patients. The most frequently
      considered factor in both assessments was chemotherapy agents in the backbone (88
      % of investigator and 93 % of patient assessments). History of FN (83 %),
      baseline laboratory values (76 %) and age (73 %) were commonly selected at
      baseline, whereas tumor type (72 %), guidelines (62 %) and tumor stage (43 %)
      were selected most during patient assessments. Median investigator-reported FN
      risk threshold for G-CSF PP was 20 % (range 10-85 %). G-CSF PP was planned in 82
      % of patients with an FN risk at or above this threshold; therefore, almost one
      fifth of qualifying patients would not receive G-CSF PP. Physicians generally
      follow guidelines, but also consider individual patient characteristics when
      assessing FN risk and deciding on G-CSF PP. A standardized FN risk assessment may
      optimize the use of G-CSF PP, which may minimize the incidence of FN in patients
      undergoing chemotherapy with an intermediate FN risk. ClinicalTrials.gov
      Identifier: NCT01813721. 

PMID- 26315713
TI  - Nanoscale-alumina induces oxidative stress and accelerates amyloid beta (Abeta)
      production in ICR female mice.
AB  - The adverse effects of nanoscale-alumina (Al2O3-NPs) have been previously
      demonstrated in both in vitro and in vivo studies, whereas little is known about
      their mechanism of neurotoxicity. It is the goal of this research to determine
      the toxic effects of nano-alumina on human neuroblastoma SH-SY5Y and mouse
      hippocampal HT22 cells in vitro and on ICR female mice in vivo. Nano-alumina
      displayed toxic effects on SH-SY5Y cell lines in three different concentrations
      also increased aluminium abundance and induced oxidative stress in HT22 cells.
      Nano-alumina peripherally administered to ICR female mice for three weeks
      increased brain aluminium and ROS production, disturbing brain energy
      homeostasis, and led to the impairment of hippocampus-dependent memory. Most
      importantly, these nano-particles induced Alzheimer disease (AD) neuropathology
      by enhancing the amyloidogenic pathway of Amyloid Beta (Abeta) production,
      aggregation and implied the progression of neurodegeneration in the cortex and
      hippocampus of these mice. In conclusion, these data demonstrate that nano
      alumina is toxic to both cells and female mice and that prolonged exposure may
      heighten the chances of developing a neurodegenerative disease, such as AD. 

PMID- 26315715
TI  - Rheumatologist and Primary Care Management of Cardiovascular Disease Risk in
      Rheumatoid Arthritis: Patient and Provider Perspectives.
AB  - OBJECTIVE: Despite increased cardiovascular disease (CVD) risk, rheumatoid
      arthritis (RA) patients often lack CVD preventive care. We examined CVD
      preventive care processes from RA patient and provider perspectives to develop a
      process map for identifying targets for future interventions to improve CVD
      preventive care. METHODS: Thirty-one participants (15 patients, 7
      rheumatologists, and 9 primary care physicians [PCPs]) participated in interviews
      that were coded using NVivo software and analyzed using grounded theory
      techniques. RESULTS: Patients and providers reported that receipt of preventive
      care depends upon identifying and acting on risk factors, although most noted
      that both processes rarely occurred. Engagement in these processes was influenced
      by various provider-, system-, visit-, and patient-related conditions, such as
      patient activation or patients' knowledge about their risk. While nearly half of
      patients and PCPs were unaware of RA-CVD risk, all rheumatologists were aware of
      risk. Rheumatologists reported not systematically identifying risk factors, or,
      if identified, they described communicating about CVD risk factors via clinic
      notes to PCPs instead of acting directly due to perceived role boundaries. PCPs
      suggested that scheduling PCP visits could improve CVD risk management, and all
      participants viewed comanagement positively. CONCLUSION: Findings from this study
      illustrate important gaps and opportunities to support identifying and acting on
      CVD risk factors in RA patients from the provider, system, visit, and patient
      levels. Future work should investigate professional role support through improved
      guidelines, patient activation, and system-based RA-CVD preventive care
      strategies.

PMID- 26315716
TI  - Improved stereoselective bioreduction of t-butyl 6-cyano-(5R)-hydroxy-3
      oxohexanoate by Rhodotorula glutinis through heat treatment.
AB  - Optically pure t-butyl 6-cyano-(3R, 5R)-dihydroxyhexanoate ((R)-1b) is the key
      precursor for atorvastatin calcium, the most widely used cholesterol-lowering
      drug. In this work, a strain ZJB-09224 capable of asymmetrically reducing t-butyl
      6-cyano-(5R)-hydroxy-3-oxohexanoate (1a) to corresponding optically pure (R)-1b
      was successfully isolated from soil sample, identified belonging to Rhodotorula
      glutinis based on the morphology, physiological tests, and the 18S rDNA sequence
      analysis. It was found that heat treatment of cell suspension at 45  degrees C
      for 25 Min significantly improved R. glutinis ZJB-09224 stereoselectivity. The
      asymmetric bioreduction of 1a was most efficient at pH 7.5, 35  degrees C, 50 mM
      (15.0 g L-1 ) substrate concentration, 40.0 g DCW L-1 cell loading size, 0.54 M
      (60.0 g L-1 ) sodium lactate acting as co-substrate. Under these optimal
      conditions, 0.046 M (R)-1b was produced with de (diastereomeric excess) value of
      99.2% after 40 H conversion. Moreover, R. glutinis ZJB-09224 has a broad
      substrate spectrum, making it a potential tool for some valuable chiral alcohol
      pharmaceutical intermediates synthesis.

PMID- 26315717
TI  - Simulation of the Elastic and Ultimate Tensile Properties of Diamond, Graphene,
      Carbon Nanotubes, and Amorphous Carbon Using a Revised ReaxFF Parametrization.
AB  - In light of the enduring interest in using nanostructured carbon materials as
      reinforcing elements in composite materials, there is a significant need for a
      reliable computational tool capable to predict the mechanical properties, both
      elastic properties and properties at the point of fracture, in large-scale
      atomistic simulations. A revised version of the ReaxFF reactive force field
      parametrization for carbon, ReaxFFC-2013, was recently published and is notable
      because of the inclusion of density functional theory (DFT)-derived mechanical
      data for diamond and graphite in the fitting set. The purpose of the present work
      is to assess the accuracy of this new force field for predicting the mechanical
      properties for several allotropes of carbon, both in the elastic regime and
      during fracture. The initial discussion focuses on the performance of ReaxFFC
      2013 for diamond and graphene, the two carbon forms for which mechanical
      properties were included in the parametrization data set. After it is established
      that simulations conducted with the new force field yield results that agree well
      with DFT and experimental data for most properties of interest, its
      transferability to amorphous carbon and carbon nanotubes is explored. ReaxFFC
      2013 is found to produce results that, for the most part, compare favorably with
      available experimental data for single and multiwalled nanotubes and for
      amorphous carbon models prepared over a range of densities. Although there is
      opportunity for improvement in some predicted properties, the ReaxFFC-2013
      parametrization is shown to generally perform well for each form of carbon and to
      compare favorably with DFT and experimental data. 

PMID- 26315718
TI  - How to take non-knowledge seriously, or "the unexpected virtue of ignorance".
AB  - This commentary argues that we need to take ignorance and non-knowledge seriously
      in the fields of science communication and public understanding of science. As
      much as we want ignorance to disappear, it seems that it is here to stay-in the
      sciences and in the rest of society. Drawing on the vast but scattered literature
      on ignorance and non-knowledge, we suggest that paying closer attention to these
      phenomena could be beneficial for science communicators. Despite the fact that
      ignorance and non-knowledge, just like knowledge, today are highly politicized
      fields, they may also open up for new lines of inquiry and may be key to more
      pluralistic and equal democratic deliberation about science and technology.

PMID- 26315719
TI  - Crafting a public for geoengineering.
AB  - In a short period of time, climate 'geoengineering' has been added to the list of
      technoscientific issues subject to deliberative public engagement. Here, we
      analyse this rapid trajectory of publicization and explore the particular manner
      in which the possibility of intentionally altering the Earth's climate system to
      curb global warming has been incorporated into the field of 'public engagement
      with science'. We describe the initial framing of geoengineering as a singular
      object of debate and subsequent attempts to 'unframe' the issue by placing it
      within broader discursive fields. The tension implicit in these processes of
      structured debate - how to turn geoengineering into a workable object of
      deliberation without implying a commitment to its reality as a policy option -
      raises significant questions about the role of 'public engagement with science'
      scholars and methods in facilitating public debate on speculative technological
      futures.

PMID- 26315720
TI  - All models are wrong, but some are useful: Averting the 'microbial apocalypse'.

PMID- 26315721
TI  - Spiritual Well-Being in Hispanic and Non-Hispanic Survivors of Allogeneic
      Hematopoietic Stem Cell Transplantation.
AB  - Research suggests that spiritual well-being positively contributes to quality of
      life during and following cancer treatment. This relationship has not been well
      described in ethnically diverse survivors of allogeneic transplantation.  This
      study compares spiritual well-being and quality of life of Hispanic (n = 69) and
      non-Hispanic (n = 102) survivors. Hispanic participants were significantly
      younger and reported significantly greater spiritual well-being than non-Hispanic
      survivors. Survivors with higher spiritual well-being had significantly better
      quality of life. Meaning and Peace significantly predicted quality of life.
      Although Hispanic survivors report greater spiritual well-being, Meaning and
      Peace, irrespective of ethnicity, have a salutary effect on quality of life. 

PMID- 26315722
TI  - CHO expressed recombinant human lactoferrin as an adjuvant for BCG.
AB  - Lactoferrin (LF), an iron binding protein with immune modulatory activities, has
      adjuvant activity to enhance vaccine efficacy. Tuberculosis (TB) is a pulmonary
      disease caused by the pathogen Mycobacterium tuberculosis (MTB). Progressive TB
      disease is clinically defined by damaging pulmonary pathology, a result of
      inflammation due to immune reactivity. The current vaccine for TB, an attenuated
      strain of Mycobacterium bovis, Bacillus Calmette Guerin (BCG), has only limited
      efficacy to prevent adult pulmonary TB. This study examines a Chinese hamster
      ovary (CHO) expressed recombinant human LF (rHLF) to boost efficacy of the BCG
      vaccine and delay early pathology post infectious challenge. C57BL/6 mice were
      immunized with BCG, or BCG admixed with either rHLF or bovine LF (bLF; internal
      control), or remained unvaccinated. Mice were then aerosol challenged with Erdman
      MTB. All vaccinated mice demonstrated decreased organ bacterial load up to 19
      weeks post infection compared with non-vaccinated controls. Furthermore, mice
      receiving bLF or rHLF supplemented BCG vaccines showed a modest decrease in lung
      pathology developed over time, compared to the BCG vaccine alone. While mice
      vaccinated with BCG/rHLF demonstrated increased general lung inflammation at day
      7, it occurred without noticeable increase in pro-inflammatory cytokines. At
      later times, decreased pathology in the rHLF groups correlated with decreased
      inflammatory cytokines. Splenic recall to BCG antigens showed BCG/rHLF
      vaccination increased production of IFN-gamma, IL-6, and GM-CSF compared to
      naive, BCG, and BCG/bLF groups. Analysis of T cell stimulating functions of bone
      marrow derived macrophages and dendritic cells treated with BCG/bLF or BCG/rHLF
      showed decreases in IL-10 production when co-cultured with sensitized CD4 and CD8
      T cells, compared to those cultured with macrophages/dendritic cells treated with
      BCG without LF. These results indicate that addition of rHLF to the BCG vaccine
      can modulate development of host pathology early post infectious challenge, most
      likely through host immune regulation affecting hypersensitive responses. 

PMID- 26315723
TI  - Seizures in an immunocompromised adolescent: a case report.
AB  - INTRODUCTION: Tuberculosis is a progressive and disabling infection predominantly
      seen in low-income and middle-income countries. Immunocompromised patients are at
      a higher risk of contracting tuberculosis than the healthy population. The
      presentation may also be atypical, leading to delay in diagnosis. We report the
      first case of tuberculous cerebral vasculitis presenting with epilepsia partialis
      continua. CASE PRESENTATION: A 17-year-old adolescent boy of Sri Lankan Moor
      heritage was taking long-term immunosuppressants for nephrotic syndrome. He
      presented to hospital with focal fits affecting his left arm. He later developed
      choreiform movements of the same arm, progressing to epilepsia partialis continua
      and weakness. The gradually evolving focal neurological signs and underlying
      immunosuppression raised the possibility of localized cerebral infection or
      inflammation. Analysis of his cerebrospinal fluid showed lymphocytosis with
      normal cellular morphology. Magnetic resonance imaging was suggestive of
      progressive vasculitic infarctions of the cerebral cortex and basal ganglia.
      There was no evidence of active autoimmune or viral disease on hematological
      investigations, but molecular amplification detected Mycobacterium tuberculosis
      in his cerebrospinal fluid. Although our patient had been established on
      isoniazid preventive treatment for eight months before the episode, tuberculosis
      was nonetheless considered to be the most likely cause of the cerebral
      vasculitis. He was treated with a trial of anti-tuberculosis treatment, including
      streptomycin and adjunctive steroids, and made an uneventful recovery.
      CONCLUSION: Clinicians should have a high index of suspicion for tuberculosis
      infection in patients with compromised immunity and other risk factors. The
      pathophysiological mechanisms underpinning cerebral vasculitis and epilepsia
      partialis continua are not completely understood. The efficacy of isoniazid
      prophylaxis in patients with immune suppression warrants further study. We
      present a regimen that successfully treated tuberculous cerebral vasculitis.

PMID- 26315724
TI  - Alternating high and low climate variability: The context of natural selection
      and speciation in Plio-Pleistocene hominin evolution.
AB  - Interaction of orbital insolation cycles defines a predictive model of
      alternating phases of high- and low-climate variability for tropical East Africa
      over the past 5 million years. This model, which is described in terms of climate
      variability stages, implies repeated increases in landscape/resource instability
      and intervening periods of stability in East Africa. It predicts eight prolonged
      (>192 kyr) eras of intensified habitat instability (high variability stages) in
      which hominin evolutionary innovations are likely to have occurred, potentially
      by variability selection. The prediction that repeated shifts toward high climate
      variability affected paleoenvironments and evolution is tested in three ways. In
      the first test, deep-sea records of northeast African terrigenous dust flux
      (Sites 721/722) and eastern Mediterranean sapropels (Site 967A) show increased
      and decreased variability in concert with predicted shifts in climate
      variability. These regional measurements of climate dynamics are complemented by
      stratigraphic observations in five basins with lengthy stratigraphic and
      paleoenvironmental records: the mid-Pleistocene Olorgesailie Basin, the Plio
      Pleistocene Turkana and Olduvai Basins, and the Pliocene Tugen Hills sequence and
      Hadar Basin--all of which show that highly variable landscapes inhabited by
      hominin populations were indeed concentrated in predicted stages of prolonged
      high climate variability. Second, stringent null-model tests demonstrate a
      significant association of currently known first and last appearance datums (FADs
      and LADs) of the major hominin lineages, suites of technological behaviors, and
      dispersal events with the predicted intervals of prolonged high climate
      variability. Palynological study in the Nihewan Basin, China, provides a third
      test, which shows the occupation of highly diverse habitats in eastern Asia,
      consistent with the predicted increase in adaptability in dispersing Oldowan
      hominins. Integration of fossil, archeological, sedimentary, and paleolandscape
      evidence illustrates the potential influence of prolonged high variability on the
      origin and spread of critical adaptations and lineages in the evolution of Homo.
      The growing body of data concerning environmental dynamics supports the idea that
      the evolution of adaptability in response to climate and overall ecological
      instability represents a unifying theme in hominin evolutionary history.

PMID- 26315725
TI  - Hollow Fluffy Co3O4 Cages as Efficient Electroactive Materials for
      Supercapacitors and Oxygen Evolution Reaction.
AB  - Nano-/micrometer multiscale hierarchical structures not only provide large
      surface areas for surface redox reactions but also ensure efficient charge
      conductivity, which is of benefit for utilization in areas of electrochemical
      energy conversion and storage. Herein, hollow fluffy cages (HFC) of Co3O4,
      constructed of ultrathin nanosheets, were synthesized by the formation of Co(OH)2
      hollow cages and subsequent calcination at 250  degrees C. The large surface area
      (245.5 m2 g(-1)) of HFC Co3O4 annealed at 250  degrees C ensures the efficient
      interaction between electrolytes and electroactive components and provides more
      active sites for the surface redox reactions. The hierarchical structures
      minimize amount of the grain boundaries and facilitate the charge transfer
      process. Thin thickness of nanosheets (2-3 nm) ensures the highly active sites
      for the surface redox reactions. As a consequence, HFC Co3O4 as the
      supercapacitor electrode exhibits a superior rate capability, shows an excellent
      cycliability of 10,000 cycles at 10 A g(-1), and delivers large specific
      capacitances of 948.9 and 536.8 F g(-1) at 1 and 40 A g(-1), respectively.
      Catalytic studies of HFC Co3O4 for oxygen evolution reaction display a much
      higher turnover frequency of 1.67*10(-2) s(-1) in pH 14.0 KOH electrolyte at 400
      mV overpotential and a lower Tafel slope of 70 mV dec(-1). HFC Co3O4 with the
      efficient electrochemical activity and good stability can remain a promising
      candidate for the electrochemical energy conversion and storage.

PMID- 26315726
TI  - The interactions between SATB1 and F-actin are important for mechanisms of active
      cell death.
AB  - INTRODUCTION: The direct involvement of nuclear actin filaments in gene
      transcription and remodeling of chromatin is still debatable. However, nuclear
      localization of F-actin and its interactions with other nuclear matrix proteins
      have been reported. The aim of the study was to estimate the interactions between
      nuclear F-actin and one of the matrix proteins, special AT-rich sequence-binding
      protein 1 (SATB1), during active cell death induced in vitro by geldanamycin
      (GA). MATERIAL AND METHODS: The expression of SATB1 was modified by the
      transfection of non-aggressive breast cancer MCF-7 cells with siRNA against SATB1
      or expression plasmid with cloned cDNA of SATB1. The amount and localization of F
      actin were altered by changes of cofilin-1 (CFL1) expression in MCF-7 cells. The
      association between SATB1 and F-actin during GA-induced cell death was analyzed
      using confocal and transmission electron microscopy. RESULTS: Our studies
      revealed the colocalization between nuclear F-actin and SATB1 protein, during GA
      induced death of breast cancer MCF-7 cells. The colocalization was enhanced in
      cells with overexpressed SATB1 and cofilin-1. At the ultrastructural level the
      SATB1 and F-actin complexes were seen at the border of condensed and decondensed
      chromatin. The presence of SATB1/F-actin molecular complexes was confirmed by
      magnetic separation of F-actin and interacting proteins. CONCLUSION: We suggest
      that the molecular interactions between SATB1 and F-actin are necessary for
      active cell death to occur.

PMID- 26315727
TI  - Cytogenetic data on the threatened leafcutter ant Atta robusta Borgmeier, 1939
      (Formicidae: Myrmicinae: Attini).
AB  - The karyotype of the threatened ant species Atta robusta is described so as to
      establish the evolutionary relationships of this taxon with other leafcutter
      ants. Standard Giemsa staining, C-banding, NOR banding, fluorochromes CMA3/DAPI,
      Hsc-FA technique and Fluorescence in situ Hybridization (FISH) using 18S rDNA
      probe were conducted on a population from Aracruz, state of Espirito Santo,
      Brazil, allowing for comparisons with data available on Atta and other fungus
      growing ant species. The diploid chromosome number observed for A. robusta was
      2n=22, and the karyotypic formula was 18m+2sm+2st. Heterochromatic blocks were
      observed in the centromeric region of most chromosomes, where one pair of
      metacentric chromosomes is characterized by a GC-rich heterochromatic band in the
      interstitial region of its long arm. The detection of 18S rDNA using FISH
      confirmed the presence of single NOR for A. robusta. This is the first report of
      rDNA 18S detection using FISH for leafcutter ants. The cytogenetic results of
      this study confirm the information available for Atta and allow us to confirm the
      conserved chromosome number, morphology and banding pattern within the genus for
      the taxa studied to date, which included species from three out of the four
      groups of Atta indicated by molecular data. The accumulation of cytogenetic data
      on fungus-growing ants enhances the understanding of the genomic evolutionary
      patterns of Atta, since it belongs to a group of recent origin between the most
      well studied ants. Cytogenetic data does not indicate restrictions in relocation
      or reintroduction in areas where populations were extinct due to the conserved
      karyotype. This study allows for cytogenetic comparison of A. robusta with other
      ants of Atta, emphasizing the importance of chromosomal information for species
      conservation. 

PMID- 26315728
TI  - Surgical and medical treatment in patients with acute severe ulcerative colitis.
AB  - Ulcerative colitis (UC) is a chronic inflammatory disease of the mucosa of the
      colorectum. The treatment of UC depends on the severity of symptoms and the
      extent of the disease. Acute severe colitis (ASC) occurs in 12-25% of patients
      with UC. Patients with ASC must be managed by a multidisciplinary team. Medically
      or surgically aggressive treatment is carried out with the final aim of reducing
      mortality. Intravenous administration of corticosteroids is the mainstay of the
      therapy. Medical rescue therapy based on cyclosporine or infliximab should be
      considered if there is no response to corticosteroids for 3 days. If there has
      been no response to medical rescue therapy after 4-7 days, the patient must
      undergo colectomy in emergency surgery. Prolonged observation is
      counterproductive, as over time it increases the risk of toxic megacolon and
      perforation, with a very high mortality rate. The best potential treatment is
      subtotal colectomy with ileostomy and preservation of the rectum. Emergency
      surgery in UC should not be seen as a last chance, but can be considered as a
      life-saving procedure. Colectomies in emergency setting are characterized by high
      morbidity rates but the mortality is low. 

PMID- 26315730
TI  - A Colorimetric and Fluorescent Sensor Based on Novel Iminocoumarin Precursor for
      Pd(2+) Dectection in Aqueous Solution.
AB  - A novel iminocoumarin precursor L was designed and well characterized. Sensor L
      showed high selectivity toward Pd(2+) in aqueous solution (CH3CN:H2O, v/v, 1:1)
      with a detection limit is 2.1 * 10(-7)M. Iminocoumarin was formed when added
      Pd(2+) to the solution of L by removing the propargylic group.

PMID- 26315729
TI  - A Study on Spectro-Analytical Aspects, DNA - Interaction, Photo-Cleavage, Radical
      Scavenging, Cytotoxic Activities, Antibacterial and Docking Properties of 3 - (1 
      (6 - methoxybenzo [d] thiazol - 2 - ylimino) ethyl) - 6 - methyl - 3H - pyran -
      2, 4 - dione and its Metal Complexes.
AB  - The focus of the present work is on the design, synthesis, characterization, DNA
      interaction, photo-cleavage, radical scavenging, in-vitro cytotoxicity,
      antimicrobial, docking and kinetic studies of Cu (II), Cd (II), Ce (IV) and Zr
      (IV) metal complexes of an imine derivative, 3 - (1 - (6 - methoxybenzo [d]
      thiazol - 2 - ylimino) ethyl) - 6 - methyl - 3H - pyran - 2, 4 - dione. The
      investigation of metal ligand interactions for the determination of composition
      of metal complexes, corresponding kinetic studies and antioxidant activity in
      solution was carried out by spectrophotometric methods. The synthesized metal
      complexes were characterized by EDX analysis, Mass, IR, (1)H-NMR, (13)C-NMR and
      UV-Visible spectra. DNA binding studies of metal complexes with Calf thymus (CT)
      DNA were carried out at room temperature by employing UV-Vis electron absorption,
      fluorescence emission and viscosity measurement techniques. The results revealed
      that these complexes interact with DNA through intercalation. The results of in
      vitro antibacterial studies showed the enhanced activity of chelating agent in
      metal chelated form and thus inferring scope for further development of new
      therapeutic drugs. Cell viability experiments indicated that all complexes showed
      significant dose dependent cytotoxicity in selected cell lines. The molecular
      modeling and docking studies were carried out with energy minimized structures of
      metal complexes to identify the receptor to metal interactions. 

PMID- 26315731
TI  - Biomechanical Modeling to Improve Coronary Artery Bifurcation Stenting: Expert
      Review Document on Techniques and Clinical Implementation.
AB  - Treatment of coronary bifurcation lesions remains an ongoing challenge for
      interventional cardiologists. Stenting of coronary bifurcations carries higher
      risk for in-stent restenosis, stent thrombosis, and recurrent clinical events.
      This review summarizes the current evidence regarding application and use of
      biomechanical modeling in the study of stent properties, local flow dynamics, and
      outcomes after percutaneous coronary interventions in bifurcation lesions.
      Biomechanical modeling of bifurcation stenting involves computational simulations
      and in vitro bench testing using subject-specific arterial geometries obtained
      from in vivo imaging. Biomechanical modeling has the potential to optimize
      stenting strategies and stent design, thereby reducing adverse outcomes. Large
      scale clinical studies are needed to establish the translation of pre-clinical
      findings to the clinical arena.

PMID- 26315732
TI  - Long-Term Clinical Outcomes of Final Kissing Ballooning in Coronary Bifurcation
      Lesions Treated With the 1-Stent Technique: Results From the COBIS II Registry
      (Korean Coronary Bifurcation Stenting Registry).
AB  - OBJECTIVES: This study investigated the impact of final kissing ballooning (FKB)
      after main vessel (MV) stenting on outcomes in patients with coronary bifurcation
      lesions after application of the 1-stent technique. BACKGROUND: Although FKB has
      been established as the standard method for bifurcation lesions treated with a 2
      stent strategy, its efficacy in a 1-stent approach is highly controversial.
      METHODS: This study enrolled 1,901 patients with a bifurcation lesion with a side
      branch diameter >=2.3 mm, treated solely with the 1-stent technique using a drug
      eluting stent from 18 centers in Korea between January 1, 2003 and December 31,
      2009. The primary outcome was major adverse cardiac events (MACE)-cardiac death,
      myocardial infarction, or target lesion revascularization. Propensity score
      matching analysis was also performed. RESULTS: FKB was performed in 620 patients
      and the post minimal lumen diameter of the MV and side branch was larger in the
      FKB group than in the non-FKB group. During follow-up (median 36 months), the
      incidence of MACE (adjusted hazard ratio [HR]: 0.68, 95% confidence interval
      [CI]: 0.46 to 0.99; p = 0.048) was lower in the FKB group than the non-FKB group.
      After propensity score matching (545 pairs), the FKB group had a lower incidence
      of MACE (adjusted HR: 0.50, 95% CI: 0.30 to 0.85; p = 0.01), and target lesion
      revascularization in the MV (adjusted HR: 0.51, 95% CI: 0.28 to 0.93; p = 0.03)
      and both vessels (adjusted HR: 0.47, 95% CI: 0.25 to 0.90; p = 0.02) than in the
      non-FKB group. CONCLUSIONS: In coronary bifurcation lesions, we demonstrated that
      the 1-stent technique with FKB was associated with a favorable long-term clinical
      outcome, mainly driven by the reduction of target lesion revascularization in the
      MV or both vessels as a result of an increase in minimal lumen diameter. (Korean
      Coronary Bifurcation Stenting Registry II [COBIS II]: NCT01642992).

PMID- 26315733
TI  - Comparative Analysis of Sequential Proximal Optimizing Technique Versus Kissing
      Balloon Inflation Technique in Provisional Bifurcation Stenting: Fractal Coronary
      Bifurcation Bench Test.
AB  - OBJECTIVES: This study used a fractal bifurcation bench model to compare 6
      optimization sequences for coronary bifurcation provisional stenting, including 1
      novel sequence without kissing balloon inflation (KBI), comprising initial
      proximal optimizing technique (POT) + side-branch inflation (SBI) + final POT,
      called "re-POT." BACKGROUND: In provisional bifurcation stenting, KBI fails to
      improve the rate of major adverse cardiac events. Proximal geometric deformation
      increases the rate of in-stent restenosis and target lesion revascularization.
      METHODS: A bifurcation bench model was used to compare KBI alone, KBI after POT,
      KBI with asymmetric inflation pressure after POT, and 2 sequences without KBI:
      initial POT plus SBI, and initial POT plus SBI with final POT (called "re-POT").
      For each protocol, 5 stents were tested using 2 different drug-eluting stent
      designs: that is, a total of 60 tests. RESULTS: Compared with the classic KBI
      only sequence and those associating POT with modified KBI, the re-POT sequence
      gave significantly (p < 0.05) better geometric results: it reduced SB ostium
      stent-strut obstruction from 23.2 +/- 6.0% to 5.6 +/- 8.3%, provided perfect
      proximal stent apposition with almost perfect circularity (ellipticity index
      reduced from 1.23 +/- 0.02 to 1.04 +/- 0.01), reduced proximal area overstretch
      from 24.2 +/- 7.6% to 8.0 +/- 0.4%, and reduced global strut malapposition from
      40 +/- 6.2% to 2.6 +/- 1.4%. CONCLUSIONS: In comparison with 5 other techniques,
      the re-POT sequence significantly optimized the final result of provisional
      coronary bifurcation stenting, maintaining circular geometry while significantly
      reducing SB ostium strut obstruction and global strut malapposition. These
      experimental findings confirm that provisional stenting may be optimized more
      effectively without KBI using re-POT.

PMID- 26315734
TI  - Differential Prognostic Effect Between First- and Second-Generation Drug-Eluting
      Stents in Coronary Bifurcation Lesions: Patient-Level Analysis of the Korean
      Bifurcation Pooled Cohorts.
AB  - OBJECTIVES: The purpose of this study was to investigate the differential
      clinical outcomes after percutaneous coronary intervention (PCI) for coronary
      bifurcation lesions with 1- or 2-stenting techniques using first- or second
      generation drug-eluting stents (DES). BACKGROUND: The 2-stenting technique has
      been regarded to have worse clinical outcomes than the 1-stenting technique after
      bifurcation PCI with first-generation DES. However, there has been a paucity of
      data comparing the 1- and 2-stenting techniques with the use of second-generation
      DES. METHODS: Patient-level pooled analysis was performed with 3,162 patients
      undergoing PCI using first- or second-generation DES for bifurcation lesions from
      the "Korean Bifurcation Pooled Cohorts" (COBIS [Coronary Bifurcation Stenting]
      II, EXCELLENT [Registry to Evaluate Efficacy of Xience/Promus Versus Cypher in
      Reducing Late Loss After Stenting], and RESOLUTE-Korea [Registry to Evaluate the
      Efficacy of Zotarolimus-Eluting Stent]). The 3-year clinical outcomes were
      compared between 1- and 2-stenting techniques, stratified by the type of DES.
      RESULTS: With first-generation DES, rates of target lesion failure (TLF) or
      patient-oriented composite outcome (POCO) (a composite of all death, any
      myocardial infarction, any repeat revascularization, and cerebrovascular
      accidents) at 3 years were significantly higher after the 2-stenting than the 1
      stenting technique (TLF 8.6% vs. 17.5%; p < 0.001; POCO 18.1% vs. 28.5%, p <
      0.001). With second-generation DES, however, there was no difference between 1-
      and 2-stenting techniques (TLF 5.4% vs. 5.8%; p = 0.768; POCO 11.2% vs. 12.9%; p
      = 0.995). The differential effects of 2-stenting technique on the prognosis
      according to the type of DES were also corroborated with similar results by the
      inverse probability weighted model. The 2-stenting technique was a significant
      independent predictor of TLF in first-generation DES (hazard ratio: 2.046; 95%
      confidence interval: 1.114 to 3.759; p < 0.001), but not in second-generation DES
      (hazard ratio: 0.667; 95% confidence interval: 0.247 to 1.802; p = 0.425).
      CONCLUSIONS: Patient-level pooled analysis of 3,162 patients in Korean
      Bifurcation Pooled Cohorts demonstrated that the 2-stenting technique showed
      comparable outcomes to 1-stenting technique with second-generation DES, which is
      different from the results of first-generation DES favoring the 1-stenting
      technique.

PMID- 26315735
TI  - Current Treatment of Bifurcation Lesions: Re-Examining the 1- Versus 2-Stent
      Argument.

PMID- 26315737
TI  - Unmatched Results After Double Kissing Crush Stenting Technique in Distal Left
      Main Coronary Artery Treatment?

PMID- 26315736
TI  - Clinical Outcome After DK Crush Versus Culotte Stenting of Distal Left Main
      Bifurcation Lesions: The 3-Year Follow-Up Results of the DKCRUSH-III Study.
AB  - OBJECTIVES: The present study aimed to investigate the difference in major
      adverse cardiac events (MACE) at 3 years after double-kissing (DK) crush versus
      culotte stenting for unprotected left main distal bifurcation lesions (LMDBLs).
      BACKGROUND: The multicenter and randomized DKCRUSH-III (Comparison of double
      kissing crush versus culotte stenting for unprotected distal left main
      bifurcation lesions: results from a multicenter, randomized, prospective study)
      showed that DK crush stenting was associated with fewer MACE at 1-year follow-up
      in patients with LMDBLs compared with culotte stenting. Here, we report the 3
      year clinical outcome of the DKCRUSH-III study. METHODS: A total of 419 patients
      with LMDBLs who were randomly assigned to either the DK crush or culotte group in
      the DKCRUSH-III study were followed for 3 year. The primary endpoint was the
      occurrence of a MACE at 3 years. Stent thrombosis (ST) was the safety endpoint.
      Patients were classified by simple and complex LMDBLs according to the DEFINITION
      (Definition and Impact of Complex Bifurcation Lesions on Clinical Outcomes After
      Percutaneous Coronary Intervention Using Drug-Eluting Stents) study criteria.
      RESULTS: At 3 years, MACE occurred in 49 patients the culotte group and in 17
      patients in the DK crush group (cumulative event rates of 23.7% and 8.2%,
      respectively; p < 0.001), mainly driven by increased myocardial infarction (8.2%
      vs. 3.4%, respectively; p = 0.037) and target-vessel revascularization (18.8% vs.
      5.8%, respectively; p < 0.001) between groups. Definite ST rate was 3.4% in the
      culotte group and 0% in the DK crush group (p = 0.007). Complex LMDBLs were
      associated with a higher rate of MACE (35.3%) at 3 years compared with a rate of
      8.1% in patients with simple LMDBLs (p < 0.001), with an extremely higher rate in
      the culotte group (51.5% vs. 15.1%, p < 0.001). CONCLUSIONS: Culotte stenting for
      LMDBLs was associated with significantly increased rates of MACE and ST. (Double
      Kissing [DK] Crush Versus Culotte Stenting for the Treatment of Unprotected
      Distal Left Main Bifurcation Lesions: DKCRUSH-III, a Multicenter Randomized Study
      Comparing Double-Stent Techniques; ChiCTR-TRC-11001877).

PMID- 26315739
TI  - Atrial Fibrillation and Transcatheter Aortic Valve Replacement: The Burden of
      Advanced Cardiovascular Disease in Aortic Stenosis.

PMID- 26315738
TI  - Baseline Characteristics and Prognostic Implications of Pre-Existing and New
      Onset Atrial Fibrillation After Transcatheter Aortic Valve Implantation: Results
      From the FRANCE-2 Registry.
AB  - OBJECTIVES: The aim of this study was to determine baseline characteristics and
      clinical outcomes of patients with pre-existing atrial fibrillation (AF) and of
      patients who presented with new-onset AF after transcatheter aortic valve
      implantation (TAVI). BACKGROUND: Little is known regarding the impact of AF after
      TAVI. METHODS: The FRANCE-2 registry included all patients undergoing TAVI (N =
      3,933) in France in 2010 and 2011. New-onset AF was defined as the occurrence of
      AF post-procedure in a patient with no documented history of AF. RESULTS: AF was
      documented before TAVI in 25.8% of patients. New-onset AF was observed in 174
      patients after TAVI among patients without a history of pre-existing AF (6.0%).
      At 1 year, the rates of all-cause death (26.5 vs. 16.6%, respectively; p < 0.001)
      and cardiovascular death (11.5 vs. 7.8%, respectively; p < 0.001) were
      significantly higher in patients with pre-existing AF compared with those without
      AF. Rehospitalization for worsening heart failure and New York Heart Association
      functional class was also higher in patients with pre-existing AF versus those
      without, resulting in a higher rate of combined efficacy endpoint in this group
      (p < 0.001). A history of stroke, surgical (nontransfemoral) approach,
      cardiological, and hemorrhagic procedure-related events were all independently
      related to the occurrence of new-onset post-procedural AF. New-onset AF in
      patients without pre-existing AF was associated with a higher rate of combined
      safety endpoint at 30 days (p < 0.001) and a higher rate of both all-cause death
      and combined efficacy endpoint at 1 year (p = 0.003 and p = 0.02, respectively).
      CONCLUSIONS: Pre-existing and new-onset AF are both associated with higher
      mortality and morbidity after TAVI.

PMID- 26315714
TI  - International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin
      Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli
      [corrected].
AB  - The renin angiotensin system (RAS) produced hormone peptides regulate many vital
      body functions. Dysfunctional signaling by receptors for RAS peptides leads to
      pathologic states. Nearly half of humanity today would likely benefit from modern
      drugs targeting these receptors. The receptors for RAS peptides consist of three
      G-protein-coupled receptors-the angiotensin II type 1 receptor (AT1 receptor),
      the angiotensin II type 2 receptor (AT2 receptor), the MAS receptor-and a type II
      trans-membrane zinc protein-the candidate angiotensin IV receptor (AngIV binding
      site). The prorenin receptor is a relatively new contender for consideration, but
      is not included here because the role of prorenin receptor as an independent
      endocrine mediator is presently unclear. The full spectrum of biologic
      characteristics of these receptors is still evolving, but there is evidence
      establishing unique roles of each receptor in cardiovascular, hemodynamic,
      neurologic, renal, and endothelial functions, as well as in cell proliferation,
      survival, matrix-cell interaction, and inflammation. Therapeutic agents targeted
      to these receptors are either in active use in clinical intervention of major
      common diseases or under evaluation for repurposing in many other disorders.
      Broad-spectrum influence these receptors produce in complex pathophysiological
      context in our body highlights their role as precise interpreters of distinctive
      angiotensinergic peptide cues. This review article summarizes findings published
      in the last 15 years on the structure, pharmacology, signaling, physiology, and
      disease states related to angiotensin receptors. We also discuss the challenges
      the pharmacologist presently faces in formally accepting newer members as
      established angiotensin receptors and emphasize necessary future developments.

PMID- 26315740
TI  - Treatment of Symptomatic Severe Aortic Stenosis With a Novel Resheathable Supra
      Annular Self-Expanding Transcatheter Aortic Valve System.
AB  - OBJECTIVES: The purpose of this study was to prospectively evaluate the safety
      and clinical performance of the CoreValve Evolut R transcatheter aortic valve
      replacement (TAVR) system (Medtronic, Inc., Minneapolis, Minnesota) in a single
      arm, multicenter pivotal study in high- or extreme-risk patients with symptomatic
      aortic valve stenosis. BACKGROUND: Although outcomes following TAVR are
      improving, challenges still exist. The repositionable 14-F equivalent CoreValve
      Evolut R TAVR system was developed to mitigate some of these challenges. METHODS:
      Suitable patients (n = 60) underwent TAVR with a 26- or 29-mm Evolut R valve.
      Primary safety endpoints were mortality and stroke at 30 days. Primary clinical
      performance endpoints were device success per the VARC-2 (Valve Academic Research
      Consortium-2) and the percent of patients with mild or less aortic regurgitation
      24 h to 7 days post-procedure. RESULTS: Patients (66.7% female; mean age 82.8 +/-
      6.1 years; Society of Thoracic Surgeons Score 7.0 +/- 3.7%) underwent TAVR via
      the transfemoral route in 98.3%, using a 29-mm valve in 68.3% of patients. All
      attempts at repositioning were successful. No death or stroke was observed up to
      30 days. The VARC-2 overall device success rate was 78.6%. Paravalvular
      regurgitation post TAVR was mild or less in 96.6%, moderate in 3.4%, and severe
      in 0% at 30 days. Major vascular complications occurred in 8.3%, and permanent
      pacemaker implantation was required in 11.7% of patients. CONCLUSIONS: The
      repositionable 14-F equivalent Evolut R TAVR system is safe and effective at
      treating high-risk symptomatic aortic stenosis patients. Repositioning was
      successful when required in all patients, with low rates of moderate or severe
      paravalvular aortic regurgitation and low permanent pacemaker implantation. (The
      Medtronic CoreValveTM Evolut RTM CE Mark Clinical Study; NCT01876420).

PMID- 26315741
TI  - Stent Repair for Complex Coarctation of Aorta.
AB  - OBJECTIVES: This study sought to determine whether several anatomic or evolving
      characteristics of the coarctation may create challenging conditions for
      treatment. BACKGROUND: Stent repair of coarctation of aorta is an alternative to
      surgical correction. METHODS: We analyzed our 21-year experience in the
      percutaneous treatment of complex coarctation of aorta. Adverse conditions for
      treatment were as follow: 1) complete interruption of the aortic arch (n = 11);
      2) associated aneurysm (n = 18); 3) complex stenosis (n = 30); and 4) the need
      for re-expansion and/or restenting (n = 21). Twenty patients (33%) belonged to
      more than 1 group. Ten interruptions were type A and 1 was type B. The mean
      length of the interrupted aorta was 9 +/- 11 mm. The associated aneurysms were
      native in 8 patients and after previous intervention in 10 patients. Aneurysm
      shapes were fusiform in 8 patients and saccular in 10. The following
      characteristics defined complex stenosis as long diffuse stenosis, very tortuous
      coarctation, or stenosis involving a main branch or an unusual location. Patients
      previously stented at an early age, required re-expansion and/or restenting after
      reaching 16 +/- 5 years of age. RESULTS: Two patients had died by 1-month follow
      up. The remaining 58 patients did well and were followed-up for a mean period of
      10 +/- 6 years. Late adverse events occurred in 3 patients (5%). All remaining
      patients are symptom-free, with normal baseline blood pressure. Imaging
      techniques revealed good patency at follow-up without associated aneurysm or
      restenosis. The actuarial survival free probability of all complex patients at 15
      years was 92%. CONCLUSIONS: Stent repair of complex coarctation of aorta is
      feasible and safe. Initial results are maintained at later follow-up.

PMID- 26315742
TI  - Overcoming Complexity: Stenting for Aortic Coarctation Comes of Age.

PMID- 26315744
TI  - Catheter-Directed Thrombolysis for Pulmonary Embolism: Where Do We Stand?

PMID- 26315745
TI  - Percutaneous Coronary Artery Bypass for Type 3 Coronary Perforation.

PMID- 26315743
TI  - A Prospective, Single-Arm, Multicenter Trial of Ultrasound-Facilitated, Catheter
      Directed, Low-Dose Fibrinolysis for Acute Massive and Submassive Pulmonary
      Embolism: The SEATTLE II Study.
AB  - OBJECTIVES: This study conducted a prospective, single-arm, multicenter trial to
      evaluate the safety and efficacy of ultrasound-facilitated, catheter-directed,
      low-dose fibrinolysis, using the EkoSonic Endovascular System (EKOS, Bothell,
      Washington). BACKGROUND: Systemic fibrinolysis for acute pulmonary embolism (PE)
      reduces cardiovascular collapse but causes hemorrhagic stroke at a rate exceeding
      2%. METHODS: Eligible patients had a proximal PE and a right ventricular (RV)-to
      left ventricular (LV) diameter ratio >=0.9 on chest computed tomography (CT). We
      included 150 patients with acute massive (n = 31) or submassive (n = 119) PE. We
      used 24 mg of tissue-plasminogen activator (t-PA) administered either as 1 mg/h
      for 24 h with a unilateral catheter or 1 mg/h/catheter for 12 h with bilateral
      catheters. The primary safety outcome was major bleeding within 72 h of procedure
      initiation. The primary efficacy outcome was the change in the chest CT-measured
      RV/LV diameter ratio within 48 h of procedure initiation. RESULTS: Mean RV/LV
      diameter ratio decreased from baseline to 48 h post-procedure (1.55 vs. 1.13;
      mean difference, -0.42; p < 0.0001). Mean pulmonary artery systolic pressure
      (51.4 mm Hg vs. 36.9 mm Hg; p < 0.0001) and modified Miller Index score (22.5 vs.
      15.8; p < 0.0001) also decreased post-procedure. One GUSTO (Global Utilization of
      Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries)
      defined severe bleed (groin hematoma with transient hypotension) and 16 GUSTO
      defined moderate bleeding events occurred in 15 patients (10%). No patient
      experienced intracranial hemorrhage. CONCLUSIONS: Ultrasound-facilitated,
      catheter-directed, low-dose fibrinolysis decreased RV dilation, reduced pulmonary
      hypertension, decreased anatomic thrombus burden, and minimized intracranial
      hemorrhage in patients with acute massive and submassive PE. (A Prospective,
      Single-arm, Multi-center Trial of EkoSonic(r) Endovascular System and Activase
      for Treatment of Acute Pulmonary Embolism (PE) [SEATTLE II]; NCT01513759).

PMID- 26315746
TI  - First-In-Man Simultaneous Transcatheter Aortic and Mitral Valve Replacement to
      Treat Severe Native Aortic and Mitral Valve Stenoses.

PMID- 26315747
TI  - The Dynamic and Evolving Realm of Interventional Cardiology: A Fellow-in
      Training's Perspective.

PMID- 26315748
TI  - Transcatheter Aortic and Mitral Valve Replacement in a Patient With Critical
      Aortic and Mitral Valve In-Ring Stenosis.

PMID- 26315749
TI  - Late Presentation of Left Main Coronary Artery Impingement Post-Transcatheter
      Aortic Valve Replacement.

PMID- 26315750
TI  - First-in-Human Transcatheter Pulmonic Valve Implantation Through a Tricuspid
      Valve Bioprosthesis to Treat Native Pulmonary Valve Regurgitation Caused by
      Carcinoid Syndrome.

PMID- 26315751
TI  - "DVT" of the Heart: A "Novel" Treatment for an Old Problem.

PMID- 26315752
TI  - Development of Late Stent Malapposition After Paclitaxel-Coated Balloon
      Angioplasty for In-Stent Neoatherosclerosis.

PMID- 26315753
TI  - Late Structural Discontinuity as a Possible Cause of Very Late Everolimus-Eluting
      Bioresorbable Scaffold Thrombosis.

PMID- 26315754
TI  - Increased Risk of Autism Spectrum Disorders in Children Born to Women With
      Systemic Lupus Erythematosus: Results From a Large Population-Based Cohort.
AB  - OBJECTIVE: In utero exposure to maternal antibodies and cytokines are potential
      risk factors for autism spectrum disorders (ASDs). The aim of this study was to
      determine whether children born to mothers with systemic lupus erythematosus
      (SLE) have an increased risk of ASD compared to children born to mothers without
      SLE. METHODS: The study population was derived from the Offspring of SLE Mothers
      Registry (OSLER), a large population-based cohort identified through healthcare
      databases in Quebec (1989-2009) comprising all women who had >=1 hospitalization
      for a delivery (stillbirth or live birth) after SLE diagnosis. As general
      population controls, a randomly selected group of women without SLE was matched
      >=4:1 to the mothers with SLE for age and year of delivery. Children born live to
      mothers with SLE and those born live to matched controls were identified, and a
      recorded diagnosis of ASD was ascertained for each child. Multivariate analyses
      were performed to adjust for parents' demographic characteristics, sex, birth
      order of the child, maternal comorbidities, and obstetric complications. RESULTS:
      In total, 509 women with SLE had 719 children, and 5,824 matched controls had
      8,493 children. Children born to women with SLE were more frequently found to
      have a diagnosis of ASD compared to controls (frequency of recorded ASDs 1.4%
      [95% confidence interval (95% CI) 0.8-2.5] versus 0.6% [95% CI 0.5-0.8]), a
      difference of 0.8% (95% CI 0.1-1.9). The mean age at ASD diagnosis was younger in
      offspring of SLE mothers (mean 3.8 years, 95% CI 1.8-5.8) compared to offspring
      of controls (mean 5.7 years, 95% CI 4.9-6.5). In primary multivariate analysis,
      SLE offspring had a substantially increased risk of ASD compared to controls
      (odds ratio 2.19, 95% CI 1.09-4.39). CONCLUSION: Compared to children from the
      general population, children born to women with SLE have an increased risk of
      ASD, although, in absolute terms, it represents a rare outcome. These hypothesis
      generating data provide direction for additional studies of maternal autoimmunity
      and ASD risk.

PMID- 26315755
TI  - Biophysics of Mechanotransduction.

PMID- 26315756
TI  - Highly active antiretroviral therapy and dyslipidemia in people living with
      HIV/AIDS in Fako Division, South West Region of Cameroon.
AB  - BACKGROUND: The advent of HAART has been associated with a profound reduction in
      morbidity and mortality from HIV/AIDS. However, side effects and toxicities
      associated with HAART may lead to an increased risk for cardiovascular diseases.
      The aim of this study was to determine the prevalence of dyslipidemia and
      determining factors of derangements in lipid profile associated with the use of
      HAART regimens in people living with HIV/AIDS in Fako Division of the South West
      Region of Cameroon. METHODS: This cross-sectional study was conducted between
      March and August 2014. Lipid profile was determined after overnight fast and
      dyslipidemia diagnosed according to the US National Cholesterol Education Program
      III criteria. Socio-demographic characteristics were also collected using a
      questionnaire. Data was analyzed using STATA; chi-square test, student's t-test,
      ANOVA and logistic regressions were computed. RESULTS: Two hundred and nine
      participants were recruited including 157 (75.1 %) on HAART and 52 (24.9 %) HAART
      naive. Antiretrovirals were drugs containing two nucleoside backbones
      (zidovudine/ /lamivudine/tenofovir) with either a non-nucleoside
      (nevirapine/efavirenz) or a protease inhibitor (lopinavir). No patient was
      treated with statins. Their mean age was 43.4 (+/-11.0) years. The mean CD4(+) T
      cell count was 425 (+/-281) cells/MUl after mean duration of HIV infection of
      54.8 (+/-43.9) months and mean duration on ART of 63.7 (+/-41.4) months. The
      prevalence of total cholesterol (>= 200 mg/dL) was 51.0 % in patients on HAART
      and 9.6 % pre-HAART patients (p < 0.0001), whereas LDL-cholesterol >= 130 mg/dL
      occurred in 36.9 % and in 7.7 % respectively, (p = 0.0001). Receiving HAART
      (adjusted odds ratio =6.24, 95 % CI: 2.33-17.45, p < 0.0001) and HIV duration of
      42 months and more (aOR = 2.26, 95 % CI: 1.16-4.42, p = 0.017) were independently
      associated with total cholesterol >= 200 mg/dL. Receiving HAART (aOR = 5.28, 95 %
      CI: 1.17-16.32, p = 0.004) was independently associated with raised LDL
      cholesterol values. The adjusted odds ratio (95 % CI) of BMI >= 25.0 kg/m(2)
      versus BMI < 25.0 kg/m(2) was 3.25 (1.44-7.34) for triglycerides >= 150 mg/dL.
      CONCLUSION: HAART regimens were significantly associated with atherogenic lipid
      profile. Lipid profile should be monitored in HIV/AIDS patients on therapy so
      that any negative effects of HAART are optimally managed.

PMID- 26315758
TI  - Prenatal diagnosis of cobblestone lissencephaly associated with Walker-Warburg
      syndrome based on a specific sonographic pattern.
AB  - We report a specific sonographic cerebral pattern of cobblestone lissencephaly
      (CL) that has not been described previously. This pattern was encountered in four
      index cases and allowed prenatal diagnosis of CL associated with Walker-Warburg
      syndrome. The pattern included both an outer echogenic band with reduced
      pericerebral space, corresponding to an infra- and supratentorial extracortical
      layer of neuroglial overmigration on pathological examination, and a 'Z'-shaped
      appearance of the brainstem. This pattern was found as early as 14 weeks'
      gestation in one of our cases.

PMID- 26315759
TI  - [A core deficit in Parkinson disease?].
AB  - INTRODUCTION: Parkinson disease is a neurodegenerative condition involving motor,
      cognitive, and linguistic deficits. It is important to know why all these
      different deficits co-occur in the affected people. This paper aims to clarify
      whether these comorbid deficits result from the selective impairment of a
      computational primitive, namely, a context-sensitive computational ability
      according to Chomsky's Hierarchy (a well-established research tool in comparative
      neuroscience). PATIENTS AND METHODS: A total of 15 medicated subjects with
      Parkinson disease and 15 controls were selected. They were matched in age and
      education. A battery of tasks was designed to test 3 different domains (motor
      capacities, cognition, and language) and 2 different computational abilities
      (context-free and context-sensitive operations). RESULTS: Significant differences
      between groups were observed only regarding the linguistic task involving context
      sensitive computations (correferences). CONCLUSIONS: The observed deficits in our
      patients with Parkinson disease cannot be explained in terms of the selective
      impairment of one only unspecific, low-level computational process. At the same
      time, differences between patients and controls are expected to be greater if the
      former are not medicated. Moreover, we should pursue in the search of (this kind
      of) computational primitives than can be selectively impaired in people with
      Parkinson disease, because they may help to achieve an earlier diagnosis of this
      condition.

PMID- 26315757
TI  - Involvement of normalized NMDA receptor and mTOR-related signaling in rapid
      antidepressant effects of Yueju and ketamine on chronically stressed mice.
AB  - Yueju, a Traditional Chinese Medicine formula, exhibited fast-onset
      antidepressant responses similar to ketamine. This study focused on assessing the
      rapid and persistent antidepressant efficacy of Yueju and ketamine in chronically
      stressed mice and its association with alternations in prefrontal N-methyl-D
      aspartate (NMDA) receptor and mammalian target of rapamycin (mTOR)-related
      activity. Chronic mild stress (CMS) led to deficits in sucrose preference test
      (SPT), forced swim test, tail suspension test, and novelty-suppressed feeding
      test, which were improved differently by acute Yueju or ketamine administration.
      The improvement in SPT started as soon as 2 hours post Yueju and ketamine but
      lasted for 6 days only by Yueju. Body weight was regained by Yueju more than
      ketamine at post-drug administration day (PAD) 6. CMS decreased phosphorylation
      of the mTOR effectors 4E-BP1 and p70S6K, their upstream regulators ERK and Akt,
      and downstream targets including synaptic protein GluR1. Yueju or ketamine
      reversed these changes at PAD 2, but only Yueju reversed phosphor-Akt at PAD 6.
      CMS selectively and lastingly increased NMDA receptor subunit NR1 expression,
      which was reversed by ketamine or Yueju at PAD 2 but only by Yueju at PAD 6.
      These findings suggest that NR1 and Akt/mTOR signaling are important therapeutic
      targets for depression. 

PMID- 26315760
TI  - Alzheimer's Disease: Genomics and Beyond.
AB  - Alzheimer's disease (AD) is a major form of senile dementia. Despite the critical
      roles of Abeta and tau in AD pathology, drugs targeting Abeta or tau have so far
      reached limited success. The advent of genomic technologies has made it possible
      to gain a more complete picture regarding the molecular network underlying the
      disease progression which may lead to discoveries of novel treatment targets. In
      this review, we will discuss recent progresses in AD research focusing on genome,
      transcriptome, epigenome, and related subjects. Advancements have been made in
      the finding of novel genetic risk factors, new hypothesis for disease mechanism,
      candidate biomarkers for early diagnosis, and potential drug targets. As an
      integration effort, we have curated relevant data in a database named AlzBase. 

PMID- 26315761
TI  - The Potential of Proteomics in Understanding Neurodegeneration.
AB  - Neurodegenerative diseases are a major health concern worldwide. Diseases such as
      Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic
      lateral sclerosis, as well as many other diseases affecting the neuromuscular
      system, are a leading cause of disability in the aging population. Presymptomatic
      diagnosis of neurodegenerative disorders is challenging due to the lack of robust
      biomarkers. Likewise, the design of effective intervention strategies is limited
      because most neurodegenerative disorders are heterogeneous in nature. Reliable
      noninvasive biomarkers are therefore urgently needed to allow presymptomatic and
      accurate diagnosis, to track disease progression, to evaluate the effectiveness
      of new treatment regimens, and to ultimately design new therapeutic intervention
      strategies. Recent biological and technological advances within the field of
      proteomic promises to provide insight into global proteome changes in
      neurodegeneration, thus allowing increased understanding of molecular pathways
      leading to neuronal cell death and the identification of biomarkers. The
      combination of gel-based techniques and mass spectrometry permits large-scale
      identification of peptide sequences in biological samples as well as the
      characterization of posttranslational protein modifications. The application of
      comparative high-throughput proteomic analyses in animal models and human tissues
      will aid in the identification of both diagnostic and prognostic biomarkers and
      will provide a platform for a future personalized medicine approach in
      neurodegeneration. 

PMID- 26315762
TI  - Proteomics Approach to Identify Biomarkers in Neurodegenerative Diseases.
AB  - This chapter examines the use of proteomics in understanding pathogenesis and
      identifying possible biomarkers in a range of neurodegenerative diseases such as
      Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis,
      Huntington's disease, and prion diseases. We have attempted to look at the
      neuroproteomic approach from a biomarker discovery point of view. Novel
      biomarkers can pave the way for new therapeutic targets and lead us to a better
      understanding of the pathogenesis involved in the neurodegenerative diseases. 

PMID- 26315763
TI  - Uncovering Neurodegenerative Protein Modifications via Proteomic Profiling.
AB  - Degenerative protein modifications (DPMs) are caused by nonenzymatic chemical
      reactions that induce changes in protein structure and function which promote
      disease initiation, pathological progression and also natural aging. These
      undesirable DPMs include oxidation, carbonylation, carbamylation, glycation,
      deamidation, isomerization, nitration, and racemization, which impart deleterious
      structural and functional changes on extracellular matrix proteins and long-lived
      cell types such as cardiomyocytes and neurons, leading to impaired overall organ
      function. Despite the obvious clinical importance of understanding DPM biology,
      the molecular mechanisms that mediate these modifications remain poorly
      understood largely due to the technical challenges associated with their study.
      However, recent advances in mass spectrometry-based proteomics technologies now
      permit global quantitative proteomic profiling of cell lines, animal models, and
      human clinical samples from a variety of different patient types. These new
      methods have not only uncovered changes in global protein expression levels but
      have also identified specific modifications of particular amino acid residues in
      protein backbones that are associated with disease progression. The nonenzymatic
      induction of DPMs as revealed by proteomic profiling can help us to better
      understand the underlying molecular pathology of protein dysfunction in human
      diseases and natural aging. This chapter discusses recent progress in
      understanding how proteomic profiling of patient samples derived from the central
      nervous system can elucidate the DPM biology of human neurodegenerative diseases.

PMID- 26315764
TI  - Comparative Proteomics for the Evaluation of Protein Expression and Modifications
      in Neurodegenerative Diseases.
AB  - Together with hypothesis-driven approaches, high-throughput differential
      proteomic analysis performed primarily not only in human cerebrospinal fluid and
      serum but also on protein content of other tissues (blood cells, muscles,
      peripheral nerves, etc.) has been used in the last years to investigate
      neurodegenerative diseases. Even if the goal for these analyses was mainly the
      discovery of neurodegenerative disorders biomarkers, the characterization of
      specific posttranslational modifications (PTMs) and the differential protein
      expression resulted in being very informative to better define the pathological
      mechanisms. In this chapter are presented and discussed the positive aspects and
      challenges of the outcomes of some of our investigations on neurological and
      neurodegenerative disease, in order to highlight the important role of protein
      PTMs studies in proteomics-based approaches. 

PMID- 26315765
TI  - Preface. Omic Studies of Neurodegenerative Disease: Part A.

PMID- 26315767
TI  - Efficient and accurate treatment of electron correlations with Correlation Matrix
      Renormalization theory.
AB  - We present an efficient method for calculating the electronic structure and total
      energy of strongly correlated electron systems. The method extends the
      traditional Gutzwiller approximation for one-particle operators to the evaluation
      of the expectation values of two particle operators in the many-electron
      Hamiltonian. The method is free of adjustable Coulomb parameters, and has no
      double counting issues in the calculation of total energy, and has the correct
      atomic limit. We demonstrate that the method describes well the bonding and
      dissociation behaviors of the hydrogen and nitrogen clusters, as well as the
      ammonia composed of hydrogen and nitrogen atoms. We also show that the method can
      satisfactorily tackle great challenging problems faced by the density functional
      theory recently discussed in the literature. The computational workload of our
      method is similar to the Hartree-Fock approach while the results are comparable
      to high-level quantum chemistry calculations. 

PMID- 26315766
TI  - Quality Markers in Cardiology. Main Markers to Measure Quality of Results
      (Outcomes) and Quality Measures Related to Better Results in Clinical Practice
      (Performance Metrics). INCARDIO (Indicadores de Calidad en Unidades Asistenciales
      del Area del Corazon): A SEC/SECTCV Consensus Position Paper.
AB  - Cardiology practice requires complex organization that impacts overall outcomes
      and may differ substantially among hospitals and communities. The aim of this
      consensus document is to define quality markers in cardiology, including markers
      to measure the quality of results (outcomes metrics) and quality measures related
      to better results in clinical practice (performance metrics). The document is
      mainly intended for the Spanish health care system and may serve as a basis for
      similar documents in other countries. 

PMID- 26315768
TI  - What do we know about obsessive-compulsive disorder following traumatic brain
      injury?
AB  - In addition to the well-known cognitive impairment following traumatic brain
      injury (TBI), neuropsychiatric sequelae are often reported as well. Although not
      the most common neuropsychiatric consequence of TBI, obsessive-compulsive
      disorder (OCD) has been associated with TBI. However, diagnosing new onset OCD
      secondary to TBI is complicated by the potential for cognitive impairment
      secondary to TBI masquerading as OCD. In particular, memory difficulties and
      executive dysfunction may be confused as representing obsessions and compulsions.
      Research in this area, which could guide clinical practice, remains limited. In
      addition to using Diagnostic and Statistical Manual of Mental Disorders, Fifth
      Edition (DSM-V) criteria, neuropsychological testing and collateral interviews
      may help clinicians when considering differential diagnoses in this complex area
      of neuropsychiatry. 

PMID- 26315769
TI  - 14th International Workshop on Co-morbidities and Adverse Drug Reactions in HIV.

PMID- 26315770
TI  - Phenotypic and genotypic characterization of Brucella strains isolated from
      autochthonous livestock reveals the dominance of B. abortus biovar 3a in Nigeria.
AB  - Brucellosis is a worldwide widespread zoonosis caused by bacteria of the genus
      Brucella. Control of this disease in a given area requires an understanding of
      the Brucella species circulating in livestock and humans. However, because of the
      difficulties intrinsic to Brucella isolation and typing, such data are scarce for
      resource-poor areas. The paucity of bacteriological data and the consequent
      imperfect epidemiological picture are particularly critical for Sahelian and Sub
      Sahara African countries. Here, we report on the characterization of 34 isolates
      collected between 1976 and 2012 from cattle, sheep and horses in Nigeria. All
      isolates were identified as Brucella abortus by Bruce-ladder PCR and assigned to
      biovar 3 by conventional typing. Further analysis by enhanced AMOS-ERY PCR showed
      that all of them belonged to the 3a sub-biovar, and MLVA analysis grouped them in
      a cluster clearly distinct from that formed by European B. abortus biovar 3b
      strains. Nevertheless, MLVA detected heterogeneity within the Nigerian biovar 3a
      strains. The close genetic profiles of the isolates from cattle, sheep and
      horses, suggest that, at least in some parts of Nigeria, biovar 3a circulates
      among animal species that are not the preferential hosts of B. abortus.
      Consistent with previous genetic analyses of 7 strains from Ivory Cost, Gambia
      and Togo, the analysis of these 34 Nigerian strains supports the hypothesis that
      the B. abortus biovar 3a lineage is dominant in West African countries. 

PMID- 26315771
TI  - Orf virus infection in sheep or goats.
AB  - Orf virus, a member of the genus Parapoxvirus, is the causative agent of
      contagious ecthyma ('Orf'). It is a pathogen with worldwide distribution, causing
      significant financial losses in livestock production. The disease mainly affects
      sheep and goats, but various other ruminants and mammals have been reported to be
      infected as well. It is also a zoonotic disease, affecting mainly people who come
      in direct or indirect contact with infected animals (e.g. farmers,
      veterinarians). The disease is usually benign and self-limiting, although in many
      cases, especially in young animals, it can be persistent and even fatal.
      Production losses caused by Orf virus are believed to be underestimated, as it is
      not a notifiable disease. This review of literature presents all latest
      information regarding the virus; considerations regarding treatment and
      prevention will be also discussed. 

PMID- 26315772
TI  - Molecular and histological characterization of bovine papillomavirus in North
      West Italy.
AB  - Bovine papillomaviruses (BPVs) are group of worldwide-spread DNA virus that
      infect primarily cattle determining diseases of considerable economic relevance.
      Recently, research on BPVs, received a great impulse owing to the development of
      specific biomolecular analysis, mostly based on L1 gene sequencing, that resulted
      in the identification of new viral types. This work is aimed at the
      identification and molecular and histopathological characterization of BPVs
      circulating in North West Italy, one of the main national cattle breeding areas.
      In this study, 71 bioptic specimens were submitted both to histological
      examination and to PCR and sequencing analysis. Histopathology revealed various
      lesion types; however, no connections were demonstrated between involved viral
      types and histopathological findings. BPV DNA was demonstrated in all the
      analyzed samples and several viral types were detected. Particularly, molecular
      investigations revealed a broad diffusion of highly pathogenic BPV1 and 2
      Deltapapillomavirus and presence of BPV3 and 9 Xipapillomavirus. Two cases of co
      infection were also demonstrated. Phylogenetic analysis revealed presence of
      different clusters and therefore a noteworthy genetic variety among the analyzed
      viral types. This study provides information on the main BPVs types in North West
      Italy and our results demonstrate the complexity of viral epidemiology which is
      characterized by circulation of multiple viral types even inside single herds.
      Knowledge of the prevalence and of the variety of BPVs is a milestone for the
      development of appropriate prophylactic and therapeutic measures. 

PMID- 26315773
TI  - The rectal microbiota of cats infected with feline immunodeficiency virus
      infection and uninfected controls.
AB  - Rectal swabs were collected from 31 cats, 16 with FIV infection and 15 uninfected
      controls, to evaluate and compare the rectal bacterial microbiota in cats with
      feline immunodeficiency virus (FIV) infection and uninfected controls. The rectal
      microbiota was characterized via next generation sequencing of 16S rRNA gene (V4
      region) polymerase chain reaction products. Eighteen different phyla were
      identified. Firmicutes dominated in both groups, followed by Proteobacteria and
      Actinobacteria, but there were no significant differences between groups. When
      predominant orders are compared, FIV-infected cats had significant higher median
      relative abundances of Bifidobacteriales (P=0.022), Lactobacillales (P=0.022) and
      Aeromonadales (P=0.043). No differences were identified in the 50 most common
      genera when adjusted for false discovery rate. There were significant differences
      in community membership (Jaccard index, unifrac P=0.008, AMOVA P<0.001) and
      community structure (Yue&Clayton index, unifrac P=0.03, AMOVA P=0.005) between
      groups. However, only one metacommunity (enterotype) was identified. The rectal
      microbiota differed between cats with FIV infection and uninfected controls. Some
      of the changes that were noted have been associated with 'dysbiosis' and
      proinflammatory states in other species, so it is possible that subclinical
      alteration in the intestinal microbiota could influence the health of FIV
      infected cats. Evaluation of the reasons for microbiota alteration and the
      potential impact on cat health is required. 

PMID- 26315774
TI  - Coxiella burnetii infections in sheep or goats: an opinionated review.
AB  - Q fever is an almost ubiquitous zoonosis caused by Coxiella burnetii, which is
      able to infect several animal species, as well as humans. Cattle, sheep and goats
      are the primary animal reservoirs. In small ruminants, infections are mostly
      without clinical symptoms, however, abortions and stillbirths can occur, mainly
      during late pregnancy. Shedding of C. burnetii occurs in feces, milk and, mostly,
      in placental membranes and birth fluids. During parturition of infected small
      ruminants, bacteria from birth products become aerosolized. Transmission to
      humans mainly happens through inhalation of contaminated aerosols. In the last
      decade, there have been several, sometimes large, human Q fever outbreaks related
      to sheep and goats. In this review, we describe C. burnetii infections in sheep
      and goats, including both advantages and disadvantages of available laboratory
      techniques, as pathology, different serological tests, PCR and culture to detect
      C. burnetii. Moreover, worldwide prevalences of C. burnetii in small ruminants
      are described, as well as possibilities for treatment and prevention. Prevention
      of shedding and subsequent environmental contamination by vaccination of sheep
      and goats with a phase I vaccine are possible. In addition, compulsory
      surveillance of C. burnetii in small ruminant farms raises awareness and hygiene
      measures in farms help to decrease exposure of people to the organism. Finally,
      this review challenges how to contain an infection of C. burnetii in small
      ruminants, bearing in mind possible consequences for the human population and
      probable interference of veterinary strategies, human risk perception and
      political considerations. 

PMID- 26315775
TI  - Two novel neutralizing antigenic epitopes of the s1 subunit protein of a QX-like
      avian infectious bronchitis virus strain Sczy3 as revealed using a phage display
      peptide library.
AB  - The spike (S) protein of the infectious bronchitis virus (IBV) plays a central
      role in the pathogenicity, the immune antibody production, serotype and the
      tissue tropism. In this study, we generate 11 monoclonal antibodies (mAbs)
      against S1 subunit of IBV Sczy3 strain, and two mAbs 1D5 and 6A12 were positive
      in indirect ELISA against both His-S1 protein and the purified whole viral
      antigen. MAb 6A12 and 1D5 could recognized by other 10 IBV strains (IBVs) from
      five different genotypes, except that 1D5 had a relatively low reaction with two
      of the 10 tested IBVs. End-point neutralizing assay performed in chicken embro
      kidney (CEK) cells revealed that the neutralization titer of 6A12 and 1D5 against
      Sczy3 reached 1:44.7 and 1:40.6, respectively. After screening a phage display
      peptide library and peptide scanning, we identified two linear B-cell epitopes
      that were recognized by the mAbs 1D5 and 6A12, which corresponded to the amino
      acid sequences (87)PPQGMAW(93) and (412)IQTRTEP(418), respectively, in the IBV S1
      subunit. Sequences comparison revealed that epitope (412)IQTRTEP(418) was
      conserved among IBVs, while the epitope (87)PPQGMAW(93) was relatively variable
      among IBVs. The novel mAbs and the epitopes identified will be useful for
      developing diagnostic assays for IBV infections. 

PMID- 26315776
TI  - Development of a subunit vaccine containing recombinant chicken anemia virus VP1
      and pigeon IFN-gamma.
AB  - Chicken anemia virus (CAV) is a severe threat to the chicken industry and causes
      heavy economic losses worldwide. In this study, we evaluated the immune response
      and protective efficacy provided by a subunit vaccine containing recombinant VP1
      (rVP1) and pigeon interferon-gamma (rPiIFN-gamma). Results indicated that rPiIFN
      gamma enhanced humoral immunity elicited by rVP1 as early as 10 day after primary
      immunization and reach the high titer after secondary immunization. When compared
      to chickens immunized with rVP1, inactivated vaccine, chickens immunized with
      rVP1+rPiIFN-gamma showed faster and higher levels (p<0.05) of antibody titer. The
      CAV challenge result showed that the rVP1+rPiIFN-gamma vaccine prevent the
      reducing of hematocrit values in comparison with the rVP1 or inactivated groups.
      The relative fold inductions of mRNA expression of Th1-type (IFN-gamma), but not
      Th2-type (IL-4) cytokines in splenocytes isolated from chickens immunized with
      rVP1+rPiIFN-gamma were significantly higher than those of the rVP1 or inactivated
      vaccine groups. In conclusion, our study found that rPiIFN-gamma can enhance both
      humoral and cellular immunity elicited by an rVP1 vaccine. The rVP1+rPiIFN-gamma
      vaccine may provide a new strategy vaccine against CAV in chicken. 

PMID- 26315777
TI  - Association between Serum Sialic Acid Levels and Nonalcoholic Fatty Liver
      Disease: A Cross-Sectional Study.
AB  - BACKGROUND: To assess the association between serum sialic acid (SA) levels and
      nonalcoholic fatty liver disease (NAFLD) in a Chinese population. METHODS: A
      cross-sectional study was performed among 3,898 Chinese who took their annual
      health examination. Serum SA levels and other clinical and laboratory parameters
      were measured. RESULTS: A total of 18.11% fulfilled the diagnostic criteria of
      NAFLD. NAFLD subjects with/without metabolic syndrome (MS) had significantly
      higher serum SA levels than those without NAFLD. Serum SA levels were
      significantly and positively correlated with components of MS (body mass index,
      systolic blood pressure, diastolic blood pressure, triglyceride and fasting
      plasma glucose) in the NAFLD group. Stepwise logistic regression analysis showed
      that SA levels were significantly associated with the risk factor for NAFLD.
      Serum SA levels were negatively correlated with the FIB-4 score, and lower serum
      SA levels were independent factors predicting advanced fibrosis in subjects with
      NAFLD. CONCLUSIONS: Our results showed a significant association between serum SA
      levels and NAFLD.

PMID- 26315778
TI  - Properties of phosphorylated thymidylate synthase.
AB  - Thymidylate synthase (TS) may undergo phosphorylation endogenously in mammalian
      cells, and as a recombinant protein expressed in bacterial cells, as indicated by
      the reaction of purified enzyme protein with Pro-Q(r) Diamond Phosphoprotein Gel
      Stain (PGS). With recombinant human, mouse, rat, Trichinella spiralis and
      Caenorhabditis elegans TSs, expressed in Escherichia coli, the phosphorylated,
      compared to non-phosphorylated recombinant enzyme forms, showed a decrease in
      Vmax(app), bound their cognate mRNA (only rat enzyme studied), and repressed
      translation of their own and several heterologous mRNAs (human, rat and mouse
      enzymes studied). However, attempts to determine the modification site(s),
      whether endogenously expressed in mammalian cells, or recombinant proteins, did
      not lead to unequivocal results. Comparative ESI-MS/analysis of IEF fractions of
      TS preparations from parental and FdUrd-resistant mouse leukemia L1210 cells,
      differing in sensitivity to inactivation by FdUMP, demonstrated phosphorylation
      of Ser(10) and Ser(16) in the resistant enzyme only, although PGS staining
      pointed to the modification of both L1210 TS proteins. The TS proteins
      phosphorylated in bacterial cells were shown by (31)P NMR to be modified only on
      histidine residues, like potassium phosphoramidate (KPA)-phosphorylated TS
      proteins. NanoLC-MS/MS, enabling the use of CID and ETD peptide fragmentation
      methods, identified several phosphohistidine residues, but certain phosphoserine
      and phosphothreonine residues were also implicated. Molecular dynamics studies,
      based on the mouse TS crystal structure, allowed one to assess potential of
      several phosphorylated histidine residues to affect catalytic activity, the
      effect being phosphorylation site dependent. 

PMID- 26315779
TI  - Effectiveness of an intermediate care hospital on readmissions, mortality,
      activities of daily living and use of health care services among hospitalized
      adults aged 60 years and older--a controlled observational study.
AB  - BACKGROUND: Intermediate care is a health care model developed to optimize the
      coordination of health care services and functional independence. In Central
      Norway, an intermediate care hospital (ICH) was established in a municipality to
      improve hospital discharge and follow-up among elderly patients with chronic
      conditions and comprehensive care needs. The aim of this study was to investigate
      the effectiveness of hospital discharges to a municipality with an ICH compared
      to discharges to a municipality without an ICH. METHODS: This was a non
      randomized controlled observational study of hospitalized patients aged 60 years
      and older from two municipalities. Patients (n = 328) admitted to a general
      hospital from February 2010 through September 2011 were included in the study and
      followed for 12 months. The data were analyzed using descriptive statistics,
      analysis of covariance (ANCOVA) and Cox proportional hazard regression. RESULTS:
      Each patient discharged from the general hospital to the municipality with an ICH
      had a shorter length of stay and used on average 4.2 (p = 0.046) fewer hospital
      days during 1 year compared to patients from the municipality without an ICH.
      Otherwise, no statistical significant differences were found between the
      municipalities in terms of hospital readmissions, admissions, mortality,
      activities of daily living, primary health care utilization or total care days. A
      post hoc analysis of patients discharged to the ICH compared to the municipality
      without an ICH, showed that the ICH patients were older and frailer, but the
      outcome was similar to the main analysis. CONCLUSIONS: Having an ICH in the
      municipality facilitated shorter length of hospital stay and kept the risk of
      readmissions, mortality and post-hospitalization care needs at the same level as
      without an ICH.

PMID- 26315780
TI  - Social capital among healthcare professionals: A prospective study of its
      importance for job satisfaction, work engagement and engagement in clinical
      improvements.
AB  - BACKGROUND: Social capital can be an important resource to facilitate the needed
      improvements in quality of care and efficiency in hospitals. OBJECTIVES: To
      assess the importance of social capital (recognition, vertical trust, horizontal
      trust and reciprocity) for job satisfaction, work engagement and engagement in
      clinical improvements. DESIGN: A prospective cohort design was used. SETTINGS:
      Intensive care units and emergency, surgical and medical units at five Swedish
      hospitals with ongoing development of their processes of care. PARTICIPANTS:
      Healthcare professionals (physicians, registered nurses, assistant nurses) at
      five Swedish midsize hospitals. METHODS: The participants answered a
      questionnaire at two occasions, NN=1602 at baseline and NN=1548 at one-year
      follow-up. Mean hospital response rate was 53% at baseline and 59% at follow-up.
      Univariate, multivariate and logistic regression analyses were performed, and the
      prospective analysis was based on 477 respondents. RESULTS: Social capital was
      associated with healthcare professionals' general work engagement and job
      satisfaction. Analysis showed positive associations between all measured aspects
      of social capital and engagement in clinical improvements of patient safety and
      quality of care. The prospective analysis showed that increased social capital
      predicted increased job satisfaction, work engagement and engagement in clinical
      improvements of patient safety. CONCLUSION: Social capital is strongly related to
      job satisfaction and active engagement with clinical improvements. The findings
      contribute to a deeper knowledge of social capital as a predictive factor that
      influences patient safety and health among healthcare staff.

PMID- 26315781
TI  - A mutational analysis of the cytosolic domain of the tomato Cf-9 disease
      resistance protein shows that membrane-proximal residues are important for Avr9
      dependent necrosis.
AB  - The tomato Cf-9 gene encodes a membrane-anchored glycoprotein that imparts race
      specific resistance against the tomato leaf mould fungus Cladosporium fulvum in
      response to the avirulence protein Avr9. Although the N-terminal half of the
      extracellular leucine-rich repeat (eLRR) domain of the Cf-9 protein determines
      its specificity for Avr9, the C-terminal half, including its small cytosolic
      domain, is postulated to be involved in signalling. The cytosolic domain of Cf-9
      carries several residues that are potential sites for ubiquitinylation or
      phosphorylation, or signals for endocytic uptake. A targeted mutagenesis approach
      was employed to investigate the roles of these residues and cellular processes in
      Avr9-dependent necrosis triggered by Cf-9. Our results indicate that the membrane
      proximal region of the cytosolic domain of Cf-9 plays an important role in Cf-9
      mediated necrosis, and two amino acids within this region, a threonine (T835) and
      a proline (P838), are particularly important for Cf-9 function. An alanine
      mutation of T835 had no effect on Cf-9 function, but an aspartic acid mutation,
      which mimics phosphorylation, reduced Cf-9 function. We therefore postulate that
      phosphorylation/de-phosphorylation of T835 could act as a molecular switch to
      determine whether Cf-9 is in a primed or inactive state. Yeast two-hybrid
      analysis was used to show that the cytosolic domain of Cf-9 interacts with the
      cytosolic domain of tomato VAP27. This interaction could be disrupted by an
      alanine mutation of P838, whereas interaction with CITRX remained unaffected. We
      therefore postulate that a proline-induced kink in the membrane-proximal region
      of the cytosolic domain of Cf-9 may be important for interaction with VAP27,
      which may, in turn, be important for Cf-9 function. 

PMID- 26315782
TI  - Glycemic control and sponsor rank of military dependents with type 1 diabetes
      mellitus.
AB  - BACKGROUND: Disparities in glycemic control are reported in children with type 1
      diabetes related to differences in access to health care and socioeconomic
      status. In the US military, rank is an indicator of socioeconomic status, but all
      have complete health care access without cost. OBJECTIVE: We sought to determine
      if glycemic control in children with type 1 diabetes differs if their sponsor
      (parent) is an officer vs. enlisted military service member. METHODS: We
      performed a cross-sectional retrospective chart review of children with type 1
      diabetes >1 yr duration whose parent is a military service member. RESULTS: A
      total of 281 subjects met study criteria, 136 (48.4%) having an enlisted and 145
      (51.6%) having an officer sponsor. The groups differed by race with 38.2% black
      in the enlisted and 9% black in the officer group (p < 0.001). The median
      enlisted average hemoglobin A1c (HbA1c) over the most recent year of available
      data was significantly higher than the officer group (9.2 vs. 8.4%, p < 0.001).
      The difference remained significant when controlled for age and race. Diabetes
      related hospitalizations were greater in the enlisted group (39.0 vs. 19.3%, p <
      0.001). More subjects in the officer group were on insulin pumps (54.5 vs. 28.7%,
      p < 0.001). CONCLUSION: Dependent children of enlisted service members with type
      1 diabetes have higher HbA1c levels, more diabetes-related hospitalizations, and
      are less likely to use insulin pumps than children of officers. These differences
      are likely linked to socioeconomic status and education levels given the
      universal access to health care within the military system.

PMID- 26315783
TI  - Monodisperse magnesium hydride nanoparticles uniformly self-assembled on
      graphene.
AB  - Monodisperse MgH2 nanoparticles with homogeneous distribution and a high loading
      percent are developed through hydrogenation-induced self-assembly under the
      structure-directing role of graphene. Graphene acts not only as a structural
      support, but also as a space barrier to prevent the growth of MgH2 nanoparticles
      and as a thermally conductive pathway, leading to outstanding performance. 

PMID- 26315786
TI  - Reply: To PMID 25779552.

PMID- 26315785
TI  - The role of autophagy in axonal degeneration of the optic nerve.
AB  - Different pathological conditions including glaucoma, optic neuritis, hereditary
      optic atrophy and traumatic injury lead to a degeneration of retinal ganglion
      cell axons in the optic nerve. Besides this clinical relevance, several
      experimental models employ the optic nerve as a model system to examine general
      mechanisms of axonal degeneration in the central nervous system. Several
      experimental studies have demonstrated that an activation of autophagy is a
      prominent feature of axonal degeneration in the optic nerve independent of the
      underlying pathological condition. However, the function of autophagy in axonal
      degeneration remains still unclear. Inhibition of autophagy was found to
      attenuate axonal degeneration within the first hours after optic nerve lesion.
      Other studies focusing on survival of retinal ganglion cells at later
      postlesional time points report contradicting results, where both inhibition and
      induction of autophagy were beneficial for survival, depending on the model
      system or examination time. Therefore, a more precise understanding of the role
      and the kinetics of autophagy in axonal degeneration is mandatory to develop new
      therapies for diseases of the optic nerve. Here, we review the literature on the
      pathophysiological role of autophagy in axonal degeneration in the optic nerve
      and discuss its implications for future therapeutic approaches in diseases of the
      eye and the central nervous system involving axonal degeneration. 

PMID- 26315784
TI  - Systemic treatment with a 5HT1a agonist induces anti-oxidant protection and
      preserves the retina from mitochondrial oxidative stress.
AB  - Chronic oxidative stress contributes to age related diseases including age
      related macular degeneration (AMD). Earlier work showed that the 5-hydroxy
      tryptamine 1a (5HT1a) receptor agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8
      OH-DPAT) protects retinal pigment epithelium (RPE) cells from hydrogen peroxide
      treatment and mouse retinas from oxidative insults including light injury. In our
      current experiments, RPE derived cells subjected to mitochondrial oxidative
      stress were protected from cell death by the up-regulation of anti-oxidant
      enzymes and of the metal ion chaperone metallothionein. Differentiated RPE cells
      were resistant to oxidative stress, and the expression of genes for protective
      proteins was highly increased by oxidative stress plus drug treatment. In mice
      treated with 8-OH-DPAT, the same genes (MT1, HO1, NqO1, Cat, Sod1) were induced
      in the neural retina, but the drug did not affect the expression of Sod2, the
      gene for manganese superoxide dismutase. We used a mouse strain deleted for Sod2
      in the RPE to accelerate age-related oxidative stress in the retina and to test
      the impact of 8-OH-DPAT on the photoreceptor and RPE degeneration developed in
      these mice. Treatment of mice with daily injections of the drug led to increased
      electroretinogram (ERG) amplitudes in dark-adapted mice and to a slight
      improvement in visual acuity. Most strikingly, in mice treated with a high dose
      of the drug (5 mg/kg) the structure of the RPE and Bruch's membrane and the
      normal architecture of photoreceptor outer segments were preserved. These results
      suggest that systemic treatment with this class of drugs may be useful in
      preventing geographic atrophy, the advanced form of dry AMD, which is
      characterized by RPE degeneration. 

PMID- 26315789
TI  - Popliteal Artery Entrapment Syndrome: Report of 2 Critical Aspects Cases.
AB  - Popliteal artery entrapment syndrome is a rare and underdiagnosed cause of
      claudication in young adult. The typical clinical feature is calf claudication;
      the following case reports describe 2 rare clinical aspects, acute limb ischemia
      and pulsatile mass revealing a bilateral anatomic entrapment. These cases suggest
      that an early diagnosis is mandatory to avoid a dramatic clinical outcome and to
      limit the surgical treatment to a myotomy. 

PMID- 26315788
TI  - miRNA-99b-3p functions as a potential tumor suppressor by targeting glycogen
      synthase kinase-3beta in oral squamous cell carcinoma Tca-8113 cells.
AB  - Dysregulation of microRNAs (miRNAs) has been associated with carcinogenesis in
      oral squamous cell carcinoma (OSCC). In the present study, we investigated the
      expression and function of miR-99b-3p in human OSCC. We found that the expression
      levels of miR-99b-3p decreased in 21 clinical OSCC samples (84%). Furthermore,
      ectopic expression of miR-99b-3p inhibited OSCC cell proliferation by
      downregulating glycogen synthase kinase-3beta (GSK3beta), an miR-99b-3p' target
      gene, at the mRNA and protein levels, both in vitro and in vivo. Moreover, the
      silencing of GSK3beta recapitulated the cellular and molecular effects in a
      similar manner to the overexpression of miR-99b-3p, which included inhibition of
      OSCC cell proliferation and suppression of p65 (RelA) and G1 regulators (cyclin
      D1, CDK4 and CDK6) in vitro. Our data suggest that miR-99b-3p functions as a
      tumor suppressor in OSCC via GSK3beta downregulation.

PMID- 26315787
TI  - Determinants of hypertension in a young adult Ugandan population in
      epidemiological transition-the MEPI-CVD survey.
AB  - BACKGROUND: High blood pressure is the principal risk factor for stroke, heart
      failure and kidney failure in the young population in Africa. Control of
      hypertension is associated with a larger reduction in morbidity and mortality in
      younger populations compared with the elderly; however, blood pressure control
      efforts in the young are hampered by scarcity of data on prevalence and factors
      influencing awareness, treatment and control of hypertension. We aimed to
      describe the prevalence of prehypertension and hypertension among young adults in
      a peri-urban district of Uganda and the factors associated with occurrence of
      hypertension in this population. METHODS: This cross-sectional study was
      conducted between August, 2012 and May 2013 in Wakiso district, a suburban
      district that that encircles Kampala, Uganda's capital city. We collected data on
      socio-demographic characteristics and hypertension status using a modified STEPs
      questionnaire from 3685 subjects aged 18-40 years selected by multistage cluster
      sampling. Blood pressure and anthropometric measurements were performed using
      standardized protocols. Fasting blood sugar and HIV status were determined using
      a venous blood sample. Association between hypertension status and various
      biosocial factors was assessed using logistic regression. RESULTS: The overall
      prevalence of hypertension was 15% (95% CI 14.2 - 19.6) and 40% were pre
      hypertensive. Among the 553 hypertensive participants, 76 (13.7%) were aware of
      their diagnosis and all these participants had initiated therapy with target
      blood pressure control attained in 20% of treated subjects. Hypertension was
      significantly associated with the older age-group, male sex and obesity. There
      was a significantly lower prevalence of hypertension among participants with HIV
      OR 0.6 (95% CI 0.4-0.8, P = 0.007). CONCLUSION: There is a high prevalence of
      high blood pressure in this young periurban population of Uganda with sub-optimal
      diagnosis and control. There is previously undocumented high rate of treatment, a
      unique finding that may be exploited to drive efforts to control hypertension.
      Specific programs for early diagnosis and treatment of hypertension among the
      young should be developed to improve control of hypertension. The relationship
      between HIV infection and blood pressure requires further clarification by
      longitudinal studies.

PMID- 26315790
TI  - Endovascular Treatment of Chronic Total Occlusions of the Iliac Arteries: Early
      and Midterm Results.
AB  - BACKGROUND: To examine the effects of endovascular therapy on the treatment of
      chronic total occlusions (CTOs) of the iliac arteries. METHODS: We analyzed a
      cohort of 48 patients (56 limbs) who were treated by endovascular means for iliac
      artery CTOs during a period of 4 years in 2 vascular surgery centers in Greece.
      The data were collected retrospectively and were statistically analyzed to report
      on technical success, morbidity, mortality, primary and secondary patency, and
      limb salvage through different patient and/or lesion stratifications. RESULTS:
      Recanalization was accomplished without assisting devices, and primary stenting
      was always performed. The technical success of the endovascular treatment reached
      91%. Patients experienced 4.2% major morbidity and 2.1% mortality rate. Mean
      ankle-brachial pressure index increased from 0.43 +/- 0.12 preoperatively to 0.89
      +/- 0.11 postoperatively. A median improvement by 3 Rutherford clinical
      categories was recorded at the first-month follow-up. The estimated limb salvage
      rate for patients suffering from critical limb ischemia (CLI) was 90.9% at 36
      months. Kaplan-Meier analysis estimation for overall primary and secondary
      patency rate of the treated lesions was 91.4% and 95.3%, respectively at 36
      months. There were no statistically significant differences in primary and
      secondary patency rate between patients in different clinical stages (CLI versus
      intermittent claudication), as well as between CTO lesions of different Trans
      Atlantic Inter-Society Consensus (TASC) categories (TASC B versus TASC C versus
      TASC D). There was not statistical significant difference between the technical
      success of TASC B, C, and D lesion groups. CONCLUSIONS: The endovascular
      treatment of iliac CTOs seems to be safe and feasible. The technical success of
      the procedure could be high, whereas primary and secondary patency rates seem to
      be optimal, with remarkable limb salvage rate and overall clinical improvement. A
      potential shift to an endovascular-first approach for such lesions might be
      currently justified.

PMID- 26315791
TI  - Risk Factors for Thrombosis Development in Mexican Patients.
AB  - BACKGROUND: To identify inherited factors: Protein C (PC), protein S (PS),
      antithrombin (AT), plasminogen (Plg), the activated PC resistance (APCR),
      prothrombin (PT) mutation G20210 A (PTG20210 A) and methylenetetrahydrofolate
      reductase C677 T polymorphism (MTHFR C677 T), as well as acquired-risk factors
      such as: diabetes mellitus, surgeries, smoking, obesity, hypertension, trauma,
      alcoholism, family history; and their association, in Mexican patients with
      diagnostic of thrombophilia. METHODS: Overall, 200 patients diagnosed with
      thrombophilia and 100 healthy controls. Commercial kits were used for the
      coagulometric tests and polymerase chain reaction, restriction fragment length
      polymorphism for molecular alterations. RESULTS: Alterations were found with an
      estimated prevalence to PC 0.65%, AT 2.04% and Plg 2.5%, APCR 2%, PT 20210 2%,
      and MTHFR 65%. The C677 T polymorphism of the MTHFR did not associate with
      acquired-risk factors so we can suppose that it is an independent risk factor.
      For the patients that only presented acquired-risk factors (21 of 200), the
      association smoking-alcoholism showed to be the cause of thrombosis with high
      risk. The following were also associated: smoking with AT, PC, and alcoholism;
      obesity with Plg; smoking with alcoholism, and PS deficiency. CONCLUSIONS: Risk
      factors for both primary and secondary and their association were present as a
      cause of thrombosis in the patients studied, and the possibility to suffer a
      recurrent thrombosis.

PMID- 26315792
TI  - Hybrid Endovascular Solutions for Supra-Aortic Vessels Extra-Anatomic Bypass
      Infection.
AB  - The use of extra-anatomic bypasses for the hybrid repair of thoracic aortic
      pathologies should consider the risk of vascular graft infection. Graft
      infections at cervical level are extremely rare and are associated with high
      mortality and morbidity rates. We report 2 cases of infected extra-anatomic
      bypasses for supra-aortic vessels debranching treated with a hybrid approach: re
      extra-anatomical bypass with the Viabahn Open Revascularization Technique
      (VORTEC) in the first patient and the EndoVAC approach in the second case.
      Endovascular techniques may offer bail-out solutions in a hybrid fashion to treat
      vascular graft infection in patients considered unfeasible for the conventional
      surgical repair, associated with appropriate antibiotic therapy. 

PMID- 26315793
TI  - Groin Swelling in a Four-Year-Old Boy: Primary Great Saphenous Vein Aneurysm.
AB  - Primary venous aneurysm, especially in pediatric population, is a very rare
      clinical entity. We report a case of primary great saphenous vein aneurysm in a 4
      year-old boy. He was initially suspected of suffering from inguinal hernia
      because the soft mass was detected at the inguinal region when the patient was in
      the standing position, but color Doppler ultrasonography demonstrated the
      swelling to be a great saphenous vein aneurysm. We decided that surgery was the
      best option because of potential risk for thromboembolism. 

PMID- 26315794
TI  - Treatment of a Juxtarenal Aneurysm with a Parallel Graft in the Left Renal Artery
      and Polymer-Based Technology to Seal the Entire Aneurysmal Sac.
AB  - BACKGROUND: Presenting the treatment of a juxtarenal aneurysm using a Nellix
      device combined with a chimney stent in a renal artery. CASE REPORT: A 72-year
      old woman was diagnosed with a 5.5-cm bilobed juxtarenal aneurysm. She underwent
      successful aneurysm repair with the Nellix system combined with a chimney stent
      in the left renal artery. Angio computed tomography control showed complete
      sealing of the aneurysm sac and patent chimney stent. CONCLUSIONS: Endovascular
      aneurysm sealing combined with chimney may be a valid way to treat juxtarenal
      aneurysms, and the conformable polymer-filled endobags may provide a durable seal
      around the chimney-graft preventing gutter formation.

PMID- 26315795
TI  - The Association of Publication of Center for Medicaid and Medicare Services
      Guidelines for Carotid Artery Angioplasty and Stenting (CAS) and CREST Results on
      the Utilization of CAS in Carotid Revascularization.
AB  - BACKGROUND: Since the 2004 approval of carotid artery angioplasty and stenting
      (CAS), there have been 2 seminal publications about CAS reimbursement (Center for
      Medicaid and Medicare Several guidelines [CMSG]; 2008) and clinical outcomes
      (Carotid Revascularization Endarterectomy versus Stent Trial [CREST]; 2010). We
      explored trends in CAS utilization after these publications nationally. METHODS:
      The most recent datasets of the nationwide inpatient sample (NIS) was queried for
      patients undergoing carotid revascularization. Utilization proportions of CAS
      were calculated quarterly from 2005 to 2011 for NIS. Three-time intervals related
      to CMSG and CREST publication were selected 2005-2008, 2008-2010, and after 2010.
      Logistic regression with piecewise linear trend for time was used to estimate
      different trends in CAS utilization for overall samples and for neurologically
      asymptomatic and symptomatic cases. RESULTS: The majority (95%) of the carotid
      revascularizations were performed on asymptomatic patients. Overall, CAS
      utilization constituted 12.5% of carotid revascularization procedures with a
      significant period increase of CAS; from 9.4% to 14%; P < 0.001. There was a
      small but significant decrease in the rate of CAS utilization after CMSG were
      published corresponding to a 2% decline in the odds ratio (OR) of CAS per quarter
      (OR, 0.98; 95% confidence interval, 0.97-0.99; P = 0.001). After CREST, CAS
      utilization continued to increase in both NIS but the rate of increase did not
      change significantly from the prepublication to the postpublication time
      interval. The odds of in-hospital mortality and postoperative stroke were
      independently and significantly higher for CAS patients in both overall and
      within the symptomatic cohorts. In all 3 periods of the study, and compared to
      carotid endarterectomy, the odds of mortality and postoperative stroke were
      significantly higher among patients who underwent CAS. CONCLUSIONS: Although
      overall utilization of CAS increased since 2005, it was not uniformly associated
      by the publication of CMSG or CREST. Despite increased utilization, the odds of
      adverse outcomes were independently higher among CAS patients.

PMID- 26315796
TI  - Integrated Vascular Surgery Resident Satisfaction.
AB  - BACKGROUND: This is the first survey to assess and quantify the level of
      satisfaction among the integrated vascular surgery residents. METHODS: An
      anonymous 13-question survey was electronically distributed to 225 members of the
      Society of Vascular Surgery Resident listserv. The questions were a combination
      of multiple choice, free response, and 5-point Leichhardt scale. Satisfaction was
      defined as a score of 3 or higher on a 5-point scale. RESULTS: Sixty-nine of 225
      responded to the survey with fairly equal distribution across the postgraduate
      years. Trainees reported high rates of satisfaction, >90%, with regards to
      faculty, educational curriculum, case selection, their peers and interactions
      with the general surgery residents and faculty. Among nonvascular rotations,
      critical care, acute care services and/or trauma and cardiothoracic were most
      frequently rated as satisfactory (100%, 95%, and 92%, respectively). Minimally
      invasive and bariatric were rated as least satisfactory at 47% and 44%.
      CONCLUSIONS: Overall vascular residents are satisfied with various aspects of
      their respective programs. Critical care, acute care services and/or trauma, and
      cardiothoracic were most universally deemed beneficial to overall education,
      whereas other rotations have more diverse responses, suggesting very program
      specific distinctions between the services.

PMID- 26315797
TI  - Abdominal Aortic Hemodynamics in Intermittent Claudication Patients at Rest and
      during Dynamic Pedaling Exercise.
AB  - BACKGROUND: Lower-extremity exercise has been shown to eliminate adverse
      hemodynamics conditions, such as low and oscillating blood flow and wall shear
      stress, in the abdominal aortas of healthy young and older adults. METHODS: We
      use cine phase-contrast magnetic resonance imaging and a custom MRI-compatible
      exercise cycle to quantify hemodynamic changes because of pedaling exercise in
      patients diagnosed with intermittent claudication. RESULTS: With only an average
      heart increase of 35 +/- 18% and exercise workload of 36 +/- 16 watts, the
      patients experienced approximately 3- and 6-fold increases in blood flow, and 4-
      and 16-fold increases in wall shear stress at the supraceliac and infrarenal
      aortic locations, respectively. Also, all oscillations in flow and shear stress
      at rest were eliminated with exercise. CONCLUSIONS: Claudication patients
      experience 3- to 4-fold lower oscillations in flow and shear stress at rest as
      compared with healthy age-matched controls, likely because of reduced distal
      arterial compliance as a result of distal atherosclerosis. The magnitude of flow
      and shear oscillatory indices may be good indicators of distal arterial
      compliance and health, and may provide predictive power for the efficacy of focal
      interventions.

PMID- 26315798
TI  - Right Brachial to Atrial Xenograft Conduit for Hemodialysis Access: A Case
      Report.
AB  - Biologic grafts may be a viable alternative to their prosthetic counterparts in
      the patients who have exhausted conventional access alternatives given their
      superior patency rates and possible resilience to infection. This is a case
      report of a 66-year-old woman with end-stage renal disease and human
      immunodeficiency virus who has had multiple failed peripheral arteriovenous (AV)
      fistulas and grafts as well as inferior vena caval obstruction necessitating a
      transhepatic catheter for hemodialysis (HD). Given the patient's comorbidities
      and history, a right brachial artery-to-atrial conduit was created for long-term
      access. Biologic bovine carotid artery was used given its decreased
      susceptibility to infection and favorable patency rates. The AV access continues
      to function at 3.5-year follow-up and remains her primary means of HD. We present
      this novel use of a biologic graft as an option in patients with central venous
      obstruction and high risk of infection requiring exotic dialysis access. 

PMID- 26315799
TI  - Magnetic Resonance Imaging in Proximal Venous Outflow Obstruction.
AB  - BACKGROUND: Proximal venous outflow obstruction (PVOO) in the abdomen and pelvis
      is increasingly recognized as an important contributor to venous disease of the
      lower extremity. There are currently no guidelines regarding a noninvasive
      screening tool for PVOO, although magnetic resonance venography (MRV) is commonly
      used in many practices. The objective of this study was to determine the value
      and utility of MRV in diagnosis and screening for PVOO. METHODS: This
      retrospective study consisted of 46 consecutive patients, all of whom presented
      with signs and/or symptoms of PVOO and were evaluated with MRV followed by
      intravascular ultrasound (IVUS) and venography. Of these 46 patients suspected to
      have PVOO based on clinical evaluation, 24 patients had PVOO confirmed with IVUS
      and venography and PVOO was not observed on IVUS and venography in the remaining
      22 patients. The MRV of these 46 patients was retrospectively reviewed in a
      blinded fashion and then correlated with IVUS and venography by 1 vascular
      surgeon. A scoring system was developed to define the types of radiography
      findings that were observed: normal, suspicious, and abnormal. RESULTS: When
      compared with IVUS and multiplane venography, the interpretation of MRV had a
      sensitivity of 100% and a specificity of 22.7%. The positive predictive value of
      MRV was 58.5%, and the negative predictive value was 100%. CONCLUSIONS: The high
      sensitivity (100%) and low specificity (22.7%) of MRV suggest that it can be a
      screening tool at best, used only to rule out PVOO; it cannot be used to confirm
      PVOO, given its a 41.5% false positive rate. Thus, the development of a
      different, noninvasive diagnostic test that can more accurately assess patients
      with suspected PVOO during the initial evaluation of their lower-extremity venous
      disease should be explored.

PMID- 26315800
TI  - Superficial Femoral Artery Stent Disruption Treated by Peripheral Endograft.
AB  - We report a case of superficial femoral artery (SFA) stent fractures (SF) with
      atypical symptoms and site of disruption. Patient was hospitalized for sudden
      onset of right thigh pain, nonrelated to steno-obstructive disease. Preoperative
      ultrasound suspected and computed tomographic angiography (CTA) confirmed
      multiple proximal SFA SFs with concurrent pseudoaneurysms. A peripheral endograft
      was deployed covering the entire SFA, achieving a complete "relining" with
      exclusion of the pseudoaneurysm. Pain disappeared and postoperative control
      demonstrated good patency of the SFA. After 1 month, patient reported no further
      events and CTA revealed patency of the endograft and exclusion of the
      pseudoaneurysm. At 1 year follow-up, Viabahn is patent with no further symptoms
      reported by the patient. 

PMID- 26315801
TI  - A Rare Case of a Massive Carotid Body Tumor in a 3-Year-Old Infant: Case
      Presentation and a Literature Review.
AB  - BACKGROUND: Paragangliomas are neuroendocrine tumors derived from the extra
      adrenal paraganglia of the autonomic nervous system. Only 3% of all
      paragangliomas are reported to occur in the head and neck region. The most common
      paraganglioma of the head and neck is the carotid body tumor. Only few cases have
      been described in the literature regarding the pediatric age group less than aged
      14 years, mostly as case reports. CASE REPORT: Our case describes a massive
      paraganglioma in the head and neck region occurring in a 3-year-old Arabic boy,
      for which surgical excision was not possible and radiotherapy resulted in a good
      clinical and radiologic response. CONCLUSIONS: Paragangliomas a rare in children
      and mostly diagnosed in a locally advanced stage. Surgery in most cases is
      difficult especially because of the proximity of the vessels; radiotherapy is
      still a good alternative for those cases.

PMID- 26315802
TI  - Using a Chimney to Make a Sandwich: Salvage of a Multibranched Thoracoabdominal
      Aortic Endograft with a Type IIIb Endoleak.
AB  - BACKGROUND: The advent of branched and fenestrated aortic endografts has
      facilitated the treatment of increasingly complex aortic pathology. The
      management of complications and endoleaks involving the branches and
      fenestrations of these grafts represents an increasingly significant clinical and
      technical challenge. METHODS: A 79-year-old woman developed a rare type IIIb
      endoleak from a tear in the graft fabric immediately posterior to the celiac axis
      branch 3 years after the placement of an off-the-shelf branched endograft for a
      type II thoracoabdominal aortic aneurysm. The patient presented urgently with
      abdominal pain and a maximal aneurysm diameter of 15.3 cm. RESULTS: The operative
      plan was to create a chimney graft completely within the original branched
      endograft to cover the defect and maintain celiac branch flow. The celiac trunk
      was accessed from a left axillary approach and access for the main endograft body
      was achieved via the left femoral artery. Two balloon-expandable covered stents
      were deployed from the celiac branch extending into the main endograft as a
      chimney and molded to 2 aortic extension cuffs to cover the fabric defect. The
      resultant configuration was a modified-sandwich graft within the original stent
      graft and resulted in successful exclusion of the endoleak. Postoperative imaging
      at 1, 6, and 12 months has demonstrated continued patency of the celiac trunk, no
      further endoleak, and a 16-mm reduction in aneurysm size. CONCLUSIONS: The
      chimney technique was successfully applied as an endovascular option to salvage a
      multibranched endograft with a significant and anatomically unfavorable defect.
      Careful follow-up and additional clinical study are required to clarify the role
      of off-the-shelf solutions in complex endoleak management.

PMID- 26315803
TI  - Reborn of Internal-External Carotid Artery Transposition as a Repair Method for
      Shotgun Injury of Neck Zone 2.
AB  - A 26-year-old male presented to the emergency center having been shot in the
      neck. Multislice computed tomography angiography revealed injury of the right
      internal carotid artery at level of the carotid bifurcation with hematoma and
      injury of right internal jugular vein. Under general anesthesia, transposition of
      internal carotid artery to external carotid artery, with ligation of internal
      jugular vein, was successfully performed. This case emphasizes the value of "old
      fashion" surgical treatment in modern endovascular age. 

PMID- 26315804
TI  - Rational Design of an Electron-Reservoir Pt(II) Complex for Efficient
      Photocatalytic Hydrogen Production from Water.
AB  - Herein we report a Pt(II) complex containing a 4,4'-bis[4-(triphenylsilyl)phenyl]
      2,2'-bipyridine ligand as a molecular catalyst for water splitting. Systematic
      studies of the electrochemical and electronic properties of this catalyst, in
      comparison with two control complexes, reveal electron-reservoir characteristics
      upon two-electron reduction. A turnover number of 510,000 was recorded by
      employing this complex as a water reduction catalyst in combination with a state
      of-the-art photosensitizer and N,N-dimethylaniline as a sacrificial electron
      donor, which represents a large improvement over the control complexes that do
      not contain the tetraphenylsilyl ligand substitution.

PMID- 26315805
TI  - Deglycosylation of Toxocara excretory-secretory antigens improves the specificity
      of the serodiagnosis for human toxocariasis.
AB  - Serodiagnosis of human toxocariasis is difficult in tropical areas where other
      helminthiasis are endemic. Many studies have shown that glycans from helminths
      may be the responsible for cross-reactions in the immunoassays. In this study, we
      have evaluated the deglycosylation of the Toxocara canis excretory-secretory
      (TES) antigens for the detection of IgG antibodies using a panel of 228 serum
      samples (58 patients with toxocariasis, 75 patients with other helminth
      infections and 95 healthy individuals) by ELISA and Western blot assays. Our
      results showed that the deglycosylation of TES antigens resulted in a single
      fraction of 26 kDa (dTES) and was able to detect IgG antibodies with a
      sensitivity and specificity of 100% in both above-mentioned assays. The rate of
      cross-reactions, observed in ELISA with TES (13.3%), was significantly reduced
      (5.3%) when the dTES antigens were used. Likewise, the cross-reactivity observed
      with the fractions of 32, 55 and 70 kDa of the TES antigens was totally
      eliminated when the dTES were used in the Western blot. All these results showed
      that the deglycosylation of the TES antigens really improves the specificity of
      the serodiagnosis of human toxocariasis in endemic areas for helminth infections.

PMID- 26315806
TI  - Likelihood of 'falling through the net' relates to contemporary prevalence of
      gestational diabetes. Reply to Ikomi A, Mannan S, Anthony R, Kiss S [letter].

PMID- 26315808
TI  - Flexible structural and electronic properties of a pentagonal B2C monolayer via
      external strain: a computational investigation.
AB  - Inspired by the recent theoretical finding that penta-graphene, composed entirely
      of carbon pentagons, is dynamically and mechanically stable [Proc. Natl. Acad.
      Sci. U. S. A., 2015, 112, 2372-2377], we computationally designed a new two
      dimensional (2D) inorganic material, a pentagonal B2C monolayer (penta-B2C), in
      which each pentagon contains three boron and two carbon atoms, the C atom is four
      coordinated with four B atoms, and all the B atoms are three-coordinated with two
      C atoms and one B atom, forming a buckled 2D network. The pentagonal B2C
      monolayer is semiconducting with a wide indirect band gap of 2.28 eV from HSE
      calculations. The absence of imaginary modes in its phonon spectrum, and the high
      melting point predicted by molecular dynamics (MD) simulations indicate its good
      stability. Interestingly, the buckled structure could be stretched to planar
      under 15% biaxial tensile strain, and the band gap will be strikingly reduced to
      0.06 eV. The semiconducting properties of penta-B2C could also be switched to
      those of a metallic semiconductor under certain biaxial strains, while uniaxial
      strains could only tune the band gaps without changing the semiconducting
      characteristics. 

PMID- 26315807
TI  - Distinct binding of amyloid imaging ligands to unique amyloid-beta deposited in
      the presubiculum of Alzheimer's disease.
AB  - Non-invasive determination of amyloid-beta peptide (Abeta) deposition with
      radioligands serves for the early diagnosis and clarification of pathogenetic
      mechanisms of Alzheimer's disease (AD). The polymorphic binding site on
      multimeric Abeta for current radioligands, however, is little understood. In this
      study, we investigated the binding of several radioligands including (11)C
      Pittsburgh Compound B ((11)C-PiB), (3)H-AZD2184, and two recently developed
      compounds, (125)I-DRM106 and (125)I-DRK092, with unique presubicular Abeta
      deposits lacking interaction with the commonly used amyloid dyes FSB. (11)C-PiB,
      (3)H-AZD2184, and (125)I-DRK092 showed overt binding to presubicular Abeta
      deposits, while (125)I-DRM106 barely bound to these aggregates despite its strong
      binding in the hippocampal CA1 sector. Unlike neuritic plaques in the CA1, Abeta
      lesions in the presubiculum were not accompanied by inflammatory gliosis enriched
      with 18-kDa translocator protein (TSPO). Thus, there are at least two different
      components in Abeta aggregates providing distinct binding sites for the current
      amyloid radioligands, and one of these binding components is distinctly present
      in the presubicular Abeta deposits. Amyloid radioligands lacking affinity for
      this component, such as (125)I-DRM106, may selectively capture Abeta deposits
      tightly associated with TSPO neuroinflammation and neurodegeneration as
      exemplified by CA1 neuritic plaques. Hence, comparative autoradiographic
      assessments of radioligand binding in CA1 and presubiculum could serve for the
      development of an amyloid PET imaging agent visualizing neurotoxicity-related
      Abeta pathologies. Non-invasive determination of amyloid-beta peptide (Abeta)
      serves for the early diagnosis and clarification of pathogenetic mechanisms of
      Alzheimer's disease (AD). We found that there are at least two different amyloid
      components in hippocampal CA1 and presubiculum providing distinct binding sites
      for the current amyloid radioligands. Comparative analysis for radioligand
      binding in these two regions could serve for developing novel imaging agents
      selectively visualizing neurotoxicity-related Abeta pathologies.

PMID- 26315809
TI  - Accuracy of (18) FDG PET-CT for treatment evaluation 3 months after completion of
      chemoradiotherapy for head and neck squamous cell carcinoma: 2-year minimum
      follow-up.
AB  - BACKGROUND: The purpose of this study was to assess the accuracy of (18) F
      fluorodeoxyglucose positron emission tomography ((18) FDG PET)-CT in detecting
      residual or recurrent disease after nonsurgical treatment for head and neck
      squamous cell carcinoma (HNSCC). METHODS: We conducted a retrospective analysis
      of patients with oral cavity, oropharynx, larynx, hypopharynx, or cervical lymph
      node location of SCC treated with chemoradiotherapy. Twelve weeks posttreatment,
      (18) FDG PET-CT results were compared to histology if residual disease was
      suspected. Patients with complete response received a minimum of 24-month follow
      up. RESULTS: Forty-seven patients were included with 40 months of median follow
      up: 46 with a squamous cell carcinoma (SCC) at the primary site and 43 in the
      neck. Sensitivity, specificity, positive predictive value (PPV), and negative
      predictive value (NPV) were 86.7%, 90%, 76.5%, and 93.1%, respectively, at the
      primary site and 100%, 97.2%, 87.5%, 100%, respectively, in the neck. CONCLUSION:
      (18) FDG PET-CT seems effective in detecting residual disease and in predicting
      recurrent disease within the first 2 years of follow-up after nonsurgical
      treatment. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1271-E1276, 2016.

PMID- 26315811
TI  - A quantitative approach to polar organic reactivity.
AB  - A method is presented which allows one to predict toxic effects which are
      triggered by the formation of covalent bonds between electron-deficient
      (electrophilic) compounds and biological electron-rich (nucleophilic) targets, as
      proteins or nucleic acids. It is based on our comprehensive nucleophilicity and
      electrophilicity scales, which we constructed as an aid for the planning of
      organic syntheses. For the construction of these scales, rate constants for the
      reactions of benzhydrylium ions (aryl2CH(+)) and structurally related quinone
      methides with nucleophiles have been measured and correlated by the equation lg
      k(20  degrees C) = sN(E + N), which yields absolute rate constants k (L mol(-1)
      s(-1)) from one parameter for electrophiles (the electrophilicity E) and two for
      nucleophiles (the nucleophilicity parameter N and the susceptibility sN). A
      freely accessible database (http://www.cup.uni-muenchen.de/oc/mayr/DBintro.html)
      is described, which presently comprises data for 1000 nucleophiles and 260
      electrophiles and provides links to the original literature reports. The kinetic
      scales are complemented by a thermodynamic counterpart, which enables one to
      calculate association constants K (L mol(-1)) of electrophiles with nucleophiles
      from the empirical Lewis acidity parameters LA and Lewis basicity parameters LB
      by the equation lg K (20 degrees C) = LA + LB. 

PMID- 26315810
TI  - Crushed Versus Integral Tablets of Ticagrelor in ST-Segment Elevation Myocardial
      Infarction Patients: A Randomized Pharmacokinetic/Pharmacodynamic Study.
AB  - OBJECTIVE: The objective of this study was to assess the pharmacokinetic and
      pharmacodynamic behavior of ticagrelor administered either as crushed (in the
      semi-upright sitting position) or as integral (in the supine position) tablets in
      ST-segment elevation myocardial infarction (STEMI) patients undergoing primary
      percutaneous coronary intervention (PCI). METHODS: We randomized 20 patients to
      ticagrelor 180 mg either as 2 integral tablets administered in the supine
      position (standard administration) or as 2 tablets crushed and dispersed,
      administered in the semi-upright sitting position. Blood samples were drawn for
      pharmacokinetic and pharmacodynamic assessment at randomization (0 h) and at 0.5,
      1, 2, and 4 h. RESULTS: At 1 h, ticagrelor plasma exposure and area under the
      plasma concentration-time curve from time zero to 1 h (AUC1) (co-primary
      endpoints) were higher in the crushed versus integral tablets group (median 586
      vs. 70.1 ng/mL and 234 vs. 24.4 ng.h/mL, respectively), with a ratio of adjusted
      geometric means (95% confidence interval [CI]) of 12.67 (2.34-68.51) [p = 0.005]
      and 19.28 (3.51-106.06) [p = 0.002], respectively. Time to maximum plasma
      concentration was shorter in the crushed versus integral tablets group (median 2
      vs. 4 h), with a ratio of adjusted geometric means (95% CI) of 0.69 (0.49-0.97)
      [p = 0.035]. Parallel findings were observed with AR-C124910XX (active
      metabolite). Platelet reactivity (VerifyNow((r))) at 1 h was lower with crushed
      versus standard administration with least squares estimates mean difference (95%
      CI) of 92 (-158.4 to 26.6) P2Y12 reaction units (p = 0.009). CONCLUSIONS: In
      patients with STEMI undergoing primary PCI, ticagrelor crushed tablets
      administered in the semi-upright sitting position seems to lead to a faster
      compared with standard administration-absorption, with stronger antiplatelet
      activity within the first hour. TRIAL REGISTRATION: ClinicalTrials.gov
      identifier: NCT02046486.

PMID- 26315812
TI  - Pseudomyogenic hemangioendothelioma/epithelioid sarcoma-like hemangioendothelioma
      of the lower limb: report of a rare case.
AB  - Pseudomyogenic hemangioendothelioma is an extremely rare soft tissue tumor, also
      named as epithelioid sarcoma-like hemangioendothelioma, which occurs more
      frequently in young adult males. It was originally recognized as a variant of
      epitheloid sarcoma, however it is now concluded as a distinctive, rarely
      metastasizing endothelial neoplasm. We present a case of pseudomyogenic
      hemangioendothelioma in the lower limb in a 49-year-old female who has a long
      course of disease and suffered from twice local recurrences and lymph node
      affection of the tumor. The mass was subcutaneous and the margins were ill
      defined. Morphologically, the tumor cells show diversity, composed of large
      spindle cells and round cells, both with abundant eocinophilic cytoplasm,
      mimicking rhybdomyoplasts and epitheloid cells respectively. The tumor cells show
      diffuse strong expression of Factor VIII, Fli-1, INI-1, vimentin, MDM2, and CDK4,
      local expression of CD31, AE1/AE3, EMA and P63, and no expression of CD34, S-100,
      actin-sm, desmin, MyoD1, and HMB45. Based on these information, this case is
      diagnosed as pseudomyogenic hemangioendothelioma after ruling out the main
      differential diagnosises including epithelioid sarcoma, malignant peripheral
      nerve sheath tumor and rhabdomyosarcoma. From this case we suggest that
      pseudomyogenic hemangioendothelioma may be confused with a variety of soft tissue
      neoplasm histologically. The clinical feature of the case of a long course of
      disease with twice local recurrences and final lymph node involvement 10 years
      after excision of the primary tumor indicates a relative indolent behavior of
      this tumor. 

PMID- 26315813
TI  - Pleural irregularity, a new ultrasound sign for the study of interstitial lung
      disease in systemic sclerosis and antisynthetase syndrome.
AB  - OBJECTIVES: To evaluate a new ultrasound sign, pleural irregularity (PI), for the
      study of interstitial lung disease (ILD) in patients with systemic sclerosis
      (SSc) and antisynthetase syndrome (ASS). METHODS: The study included patients
      from our SSc and ASS cohorts with varying degrees of ILD, enrolled from 2011 to
      2014. Chest high-resolution computed tomography (HRCT), pulmonary function tests
      (FVC and DLCO) and chest sonography were performed in each patient. Ultrasound PI
      and B-lines were quantified using a 72-sonographic point score and HRCT lung
      abnormalities were quantified using Warrick and Wells scores and categorised
      through Goh's algorithm. PI was correlated with HRCT and pulmonary function test
      parameters and its diagnostic performance to detect and classify the extent of
      ILD was evaluated and compared with B-lines. RESULTS: Thirty-seven patients were
      studied, 21 with ASS and 16 with SSc (8 without ILD). PI correlated with the
      Warrick score both in SSc (r=0.6, p=0.01) and ASS patients (r=0.6, p=0.005),
      showing a higher performance to detect ILD than using B-lines (p=0.01). In SSc
      patients PI also correlated with Wells score (r=0.7, p<0.001) and with DLCO (r=
      0.5, p=0.05), showing a high diagnostic value for detecting ILD (AUC=0.85, 95% CI
      0.64-1) and classifying it into limited or extensive (AUC=0.81, 95% CI 0.57-1). A
      modification of the Goh algorithm including PI was developed as a screening tool
      to avoid the use of HRCT in SSc patients without ultrasound evidence of extensive
      ILD. CONCLUSIONS: PI is useful for evaluation of ILD in SSc and ASS patients, and
      can be incorporated into a diagnostic algorithm in SSc patients to reducing the
      need for exposure to ionising radiation.

PMID- 26315814
TI  - How to reduce sitting time? A review of behaviour change strategies used in
      sedentary behaviour reduction interventions among adults.
AB  - Sedentary behaviour - i.e., low energy-expending waking behaviour while seated or
      lying down - is a health risk factor, even when controlling for physical
      activity. This review sought to describe the behaviour change strategies used
      within interventions that have sought to reduce sedentary behaviour in adults.
      Studies were identified through existing literature reviews, a systematic
      database search, and hand-searches of eligible papers. Interventions were
      categorised as 'very promising', 'quite promising', or 'non-promising' according
      to observed behaviour changes. Intervention functions and behaviour change
      techniques were compared across promising and non-promising interventions. Twenty
      six eligible studies reported thirty-eight interventions, of which twenty (53%)
      were worksite-based. Fifteen interventions (39%) were very promising, eight quite
      promising (21%), and fifteen non-promising (39%). Very or quite promising
      interventions tended to have targeted sedentary behaviour instead of physical
      activity. Interventions based on environmental restructuring, persuasion, or
      education were most promising. Self-monitoring, problem solving, and
      restructuring the social or physical environment were particularly promising
      behaviour change techniques. Future sedentary reduction interventions might most
      fruitfully incorporate environmental modification and self-regulatory skills
      training. The evidence base is, however, weakened by low-quality evaluation
      methods; more RCTs, employing no-treatment control groups, and collecting
      objective data are needed. 

PMID- 26315815
TI  - High-yield clicking and dissociation of doxorubicin nanoclusters exhibiting
      differential cellular uptakes and imaging.
AB  - Gold nanoparticles (AuNPs) and quantum dots (Qdots) were clicked into doxorubicin
      nanoclusters that showed enzyme-dependent dissociation behaviors for differential
      cellular uptakes and imaging. The AuNPs were co-functionalized with doxorubicin
      (DOX) and azide-terminated polymer (DOX/azide@AuNP), while an enzyme-cleavable
      peptide and alkyne-terminated polymer were sequentially conjugated on Qdot
      surface (Alkyne-MMP@Qdot). Fourier transform infrared spectroscopy (FTIR), Raman
      spectroscopy, and fluorescence imaging detected the azide and alkyne groups on
      DOX/azide@AuNP and Alkyne-MMP@Qdot, respectively, and the click-reactivity was
      also confirmed. In the presence of the catalyst, two nanoparticles were clicked
      to doxorubicin nanoclusters, which increased the volume of the particles ca. 343
      fold within 30min. Upon matrix metalloproteinase-2 (MMP-2) digestion, the
      nanoclusters were clearly dissociated into smaller particles, and the
      fluorescence of the quenched Qdot was also recovered, which suggests that the
      nanoclusters respond to MMP-2 concentrations and can thus be employed for cancer
      imaging. Confocal microscopy and an elemental analysis of the cancer cells
      revealed that the cellular uptakes of doxorubicin nanoclusters significantly
      increased at higher MMP-2 concentrations, and doxorubicin could also be cleaved
      for anti-cancer effects. In vivo and in vitro cytotoxicity assay accordingly
      showed that the cytotoxicity of doxorubicin nanoclusters against cancer cells
      increased in MMP-2-rich environments such as tumor site. Thus, these nanoclusters
      containing DOX/azide@AuNP and Alkyne-MMP@Qdot are expected to be multifunctional
      carriers for targeted anti-cancer treatments and imaging. 

PMID- 26315816
TI  - Drug delivery strategies and systems for HIV/AIDS pre-exposure prophylaxis and
      treatment.
AB  - The year 2016 will mark an important milestone - the 35th anniversary of the
      first reported cases of HIV/AIDS. Antiretroviral Therapy (ART) including Highly
      Active Antiretroviral Therapy (HAART) drug regimens is widely considered to be
      one of the greatest achievements in therapeutic drug research having transformed
      HIV infection into a chronically managed disease. Unfortunately, the lack of
      widespread preventive measures and the inability to eradicate HIV from infected
      cells highlight the significant challenges remaining today. Moving forward there
      are at least three high priority goals for anti-HIV drug delivery (DD) research:
      (1) to prevent new HIV infections from occurring, (2) to facilitate a functional
      cure, i.e., when HIV is present but the body controls it without drugs and (3) to
      eradicate established infection. Pre-exposure Prophylaxis (PrEP) represents a
      significant step forward in preventing the establishment of chronic HIV
      infection. However, the ultimate success of PrEP will depend on achieving
      sustained antiretroviral (ARV) tissue concentrations and will require strict
      patient adherence to the regimen. While first generation long acting/extended
      release (LA/ER) DD Systems (DDS) currently in development show considerable
      promise, significant DD treatment and prevention challenges persist. First, there
      is a critical need to improve cell specificity through targeting in order to
      selectively achieve efficacious drug concentrations in HIV reservoir sites to
      control/eradicate HIV as well as mitigate systemic side effects. In addition,
      approaches for reducing cellular efflux and metabolism of ARV drugs to prolong
      effective concentrations in target cells need to be developed. Finally, given the
      current understanding of HIV pathogenesis, next generation anti-HIV DDS need to
      address selective DD to the gut mucosa and lymph nodes. The current review
      focuses on the DDS technologies, critical challenges, opportunities, strategies,
      and approaches by which novel delivery systems will help iterate towards
      prevention, functional cure and eventually the eradication of HIV infection. 

PMID- 26315819
TI  - Elimination of chrysanthemum stunt viroid and chrysanthemum chlorotic mottle
      viroid from infected chrysanthemum by cryopreservation.
AB  - Chrysanthemum morifolium 'Borami' and 'Secret Pink' showing symptoms of stunt
      disease caused by chrysanthemum stunt viroid (CSVd) and 'Yellow Cap' showing
      chlorotic mottle disease caused by chrysanthemum chlorotic mottle viroid (CChMVd)
      were confirmed to be infected by the respective viroids by using reverse
      transcription polymerase chain reaction (RT-PCR). Real-time PCR results showed
      that the viroid concentrations in the infected cultivars varied between the
      different regions of origin (Chilgok, Gumi, and Gyeongsan). We applied a
      cryopreservation protocol for elimination of CSVd from naturally infected
      'Borami' collected from Gumi, showing the lowest concentration of CSVd, by
      varying several factors such as plant vitrification solutions (PVS2 and PVS3),
      duration of exposure to liquid nitrogen, shoot-tip size, and low-temperature
      treatment. The solution (PVS2) and low-temperature treatment were found to be
      critical factors determining the efficacy of viroid elimination. We optimized the
      protocol by combining of all resulted optimal factors and tested the
      applicability of the protocol in 'Borami' collected from Chilgok and Gyeongsan
      and in 'Secret Pink' from Chilgok, Gumi, and Gyeongsan, which displayed different
      viroid concentrations. We found that the elimination rates varied depending on
      the cultivar and region of origin. Similar results were observed when the
      protocol was applied to eliminate CChMVd from the 'Yellow Cap' collected from the
      same regions. Finally, we found that nested PCR is more reliable for viroid
      detection than RT-PCR. Overall, cryopreservation can be used to eliminate viroids
      from infected chrysanthemums; however, the efficacy depends on genotype and
      initial viroid concentration. 

PMID- 26315820
TI  - Advances in Boerhaavia diffusa hairy root technology: a valuable pursuit for
      identifying strain sensitivity and up-scaling factors to refine metabolite yield
      and bioactivity potentials.
AB  - The present study reports the Agrobacterium rhizogenes-mediated hairy root
      induction in of an ethno-medicinally significant herb-Boerhaavia diffusa L., for
      elucidating the underlying competence regarding its biosynthetic (i.e.
      boeravinone B and eupalitin) and bioactivity (antibacterial, antioxidant and anti
      inflammatory) potentials. Host plant-specific receptiveness towards A. rhizogenes
      strains and disparity in compatibility threshold of leaf and nodal explants were
      evident. Only leaf explants responded, attaining hairy root induction with the
      ATCC 15834 followed by A4 and SA79 strains in reducing order of transformation
      efficiency. The growth behaviours differed amongst independent rhizoclones, and
      two clones of A4 (RBH) and ATCC 15834 (RBT8) origin demonstrated higher growth
      potentials. Polymerase chain reaction amplification of rol genes confirmed their
      transformed nature. Optimization of the appropriate solvent and reverse phase
      high-performance liquid chromatography parameters relating to the targeted
      metabolite production in the selected RBH and RBT8 clones revealed higher
      accumulation of eupalitin with the RBH clone having the best result of 1.44 times
      greater yield over the control root. Compared to the selected rhizoclones, the
      control roots however showed higher boeravinone B content. Devising a modified
      "stirred-tank" reactor through equipping with marine impellers and ring spargers
      facilitated high-density RBH root biomass yield with 6.1-fold and 1.15-fold yield
      increment of the boeravinone B and eupalitin respectively compared to shake-flask
      cultures. Considering the control roots, the RBH clone revealed analogous
      antioxidant/antibacterial activities with improved anti-inflammatory potential.
      The hairy root mediated higher production of boeravinone B and eupalitin could be
      achieved for the first time in bioreactor. 

PMID- 26315817
TI  - Nano-enabled delivery of diverse payloads across complex biological barriers.
AB  - Complex biological barriers are major obstacles for preventing and treating
      disease. Nanocarriers are designed to overcome such obstacles by enhancing drug
      delivery through physiochemical barriers and improving therapeutic indices. This
      review critically examines both biological barriers and nanocarrier payloads for
      a variety of drug delivery applications. A spectrum of nanocarriers is discussed
      that have been successfully developed for improving tissue penetration for
      preventing or treating a range of infectious, inflammatory, and degenerative
      diseases. 

PMID- 26315818
TI  - Thiol-ene and photo-cleavage chemistry for controlled presentation of
      biomolecules in hydrogels.
AB  - Hydrogels have emerged as promising scaffolds in regenerative medicine for the
      delivery of biomolecules to promote healing. However, increasing evidence
      suggests that the context that biomolecules are presented to cells (e.g., as
      soluble verses tethered signals) can influence their bioactivity. A common
      approach to deliver biomolecules in hydrogels involves physically entrapping them
      within the network, such that they diffuse out over time to the surrounding
      tissues. While simple and versatile, the release profiles in such system are
      highly dependent on the molecular weight of the entrapped molecule relative to
      the network structure, and it can be difficult to control the release of two
      different signals at independent rates. In some cases, supraphysiologically high
      loadings are used to achieve therapeutic local concentrations, but uncontrolled
      release can then cause deleterious off-target side effects. In vivo, many growth
      factors and cytokines are stored in the extracellular matrix (ECM) and released
      on demand as needed during development, growth, and wound healing. Thus, emerging
      strategies in biomaterial chemistry have focused on ways to tether or sequester
      biological signals and engineer these bioactive scaffolds to signal to delivered
      cells or endogenous cells. While many strategies exist to achieve tethering of
      peptides, protein, and small molecules, this review focuses on photochemical
      methods, and their usefulness as a mild reaction that proceeds with fast kinetics
      in aqueous solutions and at physiological conditions. Photo-click and photo
      caging methods are particularly useful because one can direct light to specific
      regions of the hydrogel to achieve spatial patterning. Recent methods have even
      demonstrated reversible introduction of biomolecules to mimic the dynamic changes
      of native ECM, enabling researchers to explore how the spatial and dynamic
      context of biomolecular signals influences important cell functions. This review
      will highlight how two photochemical methods have led to important advances in
      the tissue regeneration community, namely the thiol-ene photo-click reaction for
      bioconjugation and photocleavage reactions that allow for the removal of
      protecting groups. Specific examples will be highlighted where these
      methodologies have been used to engineer hydrogels that control and direct cell
      function with the aim of inspiring their use in regenerative medicine. 

PMID- 26315822
TI  - Intravenous immunogobulin therapy for severe gastrointestinal involvement in
      systemic sclerosis.
AB  - OBJECTIVES: Gastrointestinal (GI) disease is one of the major causes of morbidity
      in patients with systemic sclerosis (SSc). The most common manifestation of GI
      disease is oesophageal involvement affecting 70-90% of patients. Severe GI
      disease is uncommon, but results in symptoms such as early satiety, pseudo
      obstruction, weight loss and malnutrition. The pathogenesis is relatively poorly
      understood, and management focuses on symptomatic control rather than
      immunomodulation. METHODS: We describe two cases of patients with SSc myositis
      overlap syndrome with severe GI involvement who demonstrated improvements in
      swallowing, early satiety and diarrhoea following the administration of
      intravenous immunoglobulin (IVIg). RESUTS: Clinical data related to the two cases
      were collected by review of medical records. CONCLUSIONS: GI complications range
      from mild symptoms to debilitating and life threatening. We propose that IVIg may
      have an immunomodulatory effect in a subset of patients with SSc myositis overlap
      syndrome.

PMID- 26315821
TI  - An antifungal protein from Ginkgo biloba binds actin and can trigger cell death.
AB  - Ginkbilobin is a short antifungal protein that had been purified and cloned from
      the seeds of the living fossil Ginkgo biloba. Homologues of this protein can be
      detected in all seed plants and the heterosporic fern Selaginella and are
      conserved with respect to domain structures, peptide motifs, and specific
      cysteine signatures. To get insight into the cellular functions of these
      conserved motifs, we expressed green fluorescent protein fusions of full-length
      and truncated ginkbilobin in tobacco BY-2 cells. We show that the signal peptide
      confers efficient secretion of ginkbilobin. When this signal peptide is either
      cleaved or masked, ginkbilobin binds and visualizes the actin cytoskeleton. This
      actin-binding activity of ginkbilobin is mediated by a specific subdomain just
      downstream of the signal peptide, and this subdomain can also coassemble with
      actin in vitro. Upon stable overexpression of this domain, we observe a specific
      delay in premitotic nuclear positioning indicative of a reduced dynamicity of
      actin. To elucidate the cellular response to the binding of this subdomain to
      actin, we use chemical engineering based on synthetic peptides comprising
      different parts of the actin-binding subdomain conjugated with the cell
      penetrating peptide BP100 and with rhodamine B as a fluorescent reporter. Binding
      of this synthetic construct to actin efficiently induces programmed cell death.
      We discuss these findings in terms of a working model, where ginkbilobin can
      activate actin-dependent cell death. 

PMID- 26315823
TI  - Near infrared reflectance spectroscopy (NIRS) analyses of nutrient composition
      and condensed tannin concentrations in carolina willow (Salix caroliniana).
AB  - Iron overload disorder has been described in a number of zoo-managed species, and
      it has been recommended to increase the tannin composition of the diet as a safe
      way to minimize iron absorption in these iron-sensitive species. The goal of this
      study was to examine the potential of near infrared reflectance spectroscopy
      (NIRS) as a rapid and simple screening tool to assess willow (Salix caroliniana)
      nutrient composition (crude protein: CP; acid detergent fiber: ADF; neutral
      detergent fiber: NDF; lignin, gross energy: GE) and condensed tannin (CT)
      concentrations. Calibration equations were developed by regression of the lab
      values from 2 years using partial least squares on n = 144 NIRS spectra to
      predict n = 20 independent validation samples. Using the full 2-year dataset,
      good prediction statistics were obtained for CP, ADF, NDF, and GE in plant leaves
      and stems (r(2 ) > 0.75). NIRS did not predict lignin concentrations reliably
      (leaves r(2)  = 0.52, stems r(2)  = 0.33); however, CTs were predicted moderately
      well (leaves r(2)  = 0.72, stems r(2)  = 0.67). These data indicate that NIRS can
      be used to quantify several key nutrients in willow leaves and stems including
      concentrations of plant secondary compounds which, depending on the bioactivity
      of the compound, may be targeted to feed iron-sensitive browsing animals.

PMID- 26315825
TI  - Total Closure of Enlarged Tracheoesophageal Puncture with Septal Button: Long
      Term Results.
AB  - Tracheoesophageal puncture enlargement in laryngectomized patients is a
      significant problem due to complications such as aspiration pneumonia. There are
      several management methods including conservative and nonconservative techniques.
      A total closure of the enlarged tracheoesophageal puncture is needed in some
      cases when conservative approaches have failed. At this point, the insertion of a
      silicone septal button in the puncture site is a useful, inexpensive, and simple
      technique. The follow-up of 4 patients managed with this technique revealed
      satisfactory long-term results. 

PMID- 26315824
TI  - Substance use among adolescent and young adult cancer survivors.
AB  - OBJECTIVE: Health-promoting behaviors are recommended to childhood cancer
      survivors (CCS) to reduce late effects resulting from cancer treatment.
      Understanding factors associated with substance use is needed, especially among
      Hispanic CCS who are underrepresented in previous studies. The objective of this
      study is to examine substance use behaviors of recently treated Hispanic and non
      Hispanic CCS. METHODS: One hundred ninety-three Los Angeles County CCS who were
      diagnosed between 2000 and 2007 (54% Hispanic; mean age 19.9 years, SD = 2.8;
      mean age at diagnosis = 12.1, SD = 3.0; mean years since diagnosis = 7.8, SD =
      2.0) provided self-reported information on substance use, demographics, clinical
      factors, religiosity, and depressive symptoms. Risk and protective factors for
      substance use were examined using multivariable logistic regression. RESULTS:
      Prevalence of 30-day substance use was 11%, 25%, and 14% for tobacco, alcohol,
      and marijuana, respectively. In controlled regression models, age was positively
      associated with tobacco use, binge drinking, and polysubstance use (use of at
      least two of the three substances). Male gender, higher depressive symptoms, and
      higher socioeconomic status were associated with greater marijuana use. In
      addition, religiosity was negatively associated with the use of all substances.
      CONCLUSIONS: The prevalence rates for substance use in this ethnically diverse
      representative sample of CCS are lower than those observed in the general
      population. Older CCS were at higher risk of substance use, and depression was
      associated with greater marijuana use. No differences by ethnicity were observed.
      Interventions for substance use prevention/cessation among CCS may be most
      effective if implemented before the age of 21 years and address mental health as
      part of survivorship care. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 26315826
TI  - Low daily energy expenditure enables giant pandas to survive on bamboo.

PMID- 26315827
TI  - Reduced graphene oxide-supported TiO2 fiber bundles with mesostructures as anode
      materials for lithium-ion batteries.
AB  - Although the synthesis of mesoporous materials is well established, the
      preparation of TiO2 fiber bundles with mesostructures, highly crystalline walls,
      and good thermal stability on the RGO nanosheets remains a challenge. Herein, a
      low-cost and environmentally friendly hydrothermal route for the synthesis of RGO
      nanosheet-supported anatase TiO2 fiber bundles with dense mesostructures is used.
      These mesostructured TiO2 -RGO materials are used for investigation of Li-ion
      insertion properties, which show a reversible capacity of 235 mA h g(-1) at 200
      mA g(-1) and 150 mA h g(-1) at 1000 mA g(-1) after 1000 cycles. The higher
      specific surface area of the new mesostructures and high conductive substrate
      (RGO nanosheets) result in excellent lithium storage performance, high-rate
      performance, and strong cycling stability of the TiO2 -RGO composites. 

PMID- 26315828
TI  - Intraarterial Microdosing: A Novel Drug Development Approach, Proof-of-Concept
      PET Study in Rats.
AB  - Intraarterial microdosing (IAM) is a novel drug development approach combining
      intraarterial drug delivery and microdosing. We aimed to demonstrate that IAM
      leads to target exposure similar to that of systemic full-dose administration but
      with minimal systemic exposure. IAM could enable the safe, inexpensive, and early
      study of novel drugs at the first-in-human stage and the study of established
      drugs in vulnerable populations. METHODS: Insulin was administered
      intraarterially (ipsilateral femoral artery) or systemically to 8 CD IGS rats
      just before blood sampling or 60-min (18)F-FDG uptake PET imaging of ipsilateral
      and contralateral leg muscles (lateral gastrocnemius) and systemic muscles
      (spinotrapezius). The (18)F-FDG uptake slope analysis was used to compare the
      interventions. Plasma levels of insulin and glucose were compared using area
      under the curve calculated by the linear trapezoidal method. A physiologically
      based computational pharmacokinetics/pharmacodynamics model was constructed to
      simulate the relationship between the administered dose and response over time.
      RESULTS: (18)F-FDG slope analysis found no difference between IAM and systemic
      full-dose slopes (0.0066 and 0.0061, respectively; 95% confidence interval [CI], 
      0.024 to 0.029; P = 0.7895), but IAM slope was statistically significantly
      greater than systemic microdose (0.0018; 95% CI, -0.045 to -0.007; P = 0.0147)
      and sham intervention (-0.0015; 95% CI, 0.023-0.058; P = 0.0052). The
      pharmacokinetics/pharmacodynamics data were used to identify model parameters
      that describe membrane insulin binding and glucose-insulin dynamics. CONCLUSION:
      Target exposure after IAM was similar to systemic full dose administration but
      with minimal systemic effects. The computational
      pharmacokinetics/pharmacodynamics model can be generalized to predict whole-body
      response. Findings should be validated in larger, controlled studies in animals
      and humans using a range of targets and classes of drugs.

PMID- 26315829
TI  - Clinical Efficacy and Safety Comparison of 177Lu-EDTMP with 153Sm-EDTMP on an
      Equidose Basis in Patients with Painful Skeletal Metastases.
AB  - This prospective study compared 177Lu-ethylene diamine tetramethylene phosphonate
      (EDTMP) with 153Sm-EDTMP for painful skeletal metastases. METHODS: Half of the 32
      patients were treated with 177Lu-EDTMP and half with 153Sm-EDTMP, at 37 MBq/kg of
      body weight. Analgesic, pain, and quality-of-life scores (EORTC, Karnofsky, ECOG)
      and bone proliferation marker were used to examine efficacy. Hematologic toxicity
      was evaluated using NCI-CTCAE and compared between groups at baseline and each
      month till 3 mo after therapy. Pain relief was categorized as complete, partial,
      minimal, or none. RESULTS: Pain relief with 177Lu-EDTMP was 80%: 50% complete,
      41.67% partial, and 8.33% minimal. Pain relief with 153Sm-EDTMP was 75%: 33.33%
      complete, 58.33% partial, and 8.33% minimal. The difference was not significant
      (P=1.000). Quality of life at 3 mo after therapy improved significantly in both
      groups as per ECOG score (P=0.014 and 0.005 for 177Lu-EDTMP and 153Sm-EDTMP,
      respectively), Karnofsky index (P=0.007 and 0.023 for 177Lu-EDTMP and 153Sm
      EDTMP, respectively), and EORTC score (P=0.004 and <0.001 for 177Lu-EDTMP and
      153Sm-EDTMP, respectively). Bone proliferation marker in responders of both
      groups dropped significantly (P=0.008 for 177Lu-EDTMP and P=0.019 for 153Sm
      EDTMP), parallel to clinical response. For 177Lu-EDTMP, anemia, leukopenia, and
      thrombocytopenia were nonserious (grade I/II) in 46.67%, 46.67%, and 20%,
      respectively, and serious (grade III/IV) in 20%, 6.67%, and 0%, respectively. For
      153Sm-EDTMP, anemia, leukopenia, and thrombocytopenia were nonserious (grade
      I/II) in 62.5%, 31.25%, and 18.75%, respectively, and serious (grade III/IV) in
      18.75%, 0%, and 6.25%, respectively. One patient treated with 153Sm-EDTMP had
      grade IV thrombocytopenia but required no blood transfusion. Differences between
      groups were not significant for either nonserious or serious toxicity. For 177Lu
      EDTMP, 3 of 12 responders experienced the flare phenomenon on the third day after
      therapy and one on the fifth day, showing no response to therapy. For 153Sm
      EDTMP, 2 of 12 responders experienced the flare phenomenon, both on the third day
      after therapy. CONCLUSION: 177Lu-EDTMP has pain response efficacy similar to that
      of 153Sm-EDTMP and is a feasible and safe alternative, especially in centers with
      no nearby access to 153Sm-EDTMP.

PMID- 26315830
TI  - Predictive Value of 99mTc-MAA SPECT for 90Y-Labeled Resin Microsphere
      Distribution in Radioembolization of Primary and Secondary Hepatic Tumors.
AB  - This study analyzed the predictive value of (99m)Tc-labeled macroaggregated
      albumin ((99m)Tc-MAA) SPECT for (90)Y-labeled resin microsphere therapy
      (radioembolization) by comparing uptake on pretherapeutic (99m)Tc-MAA SPECT with
      uptake on posttherapeutic (90)Y-bremsstrahlung SPECT. METHODS: We included 502
      patients (55% male; mean age +/- SD, 62 +/- 11 y) who underwent radioembolization
      between 2005 and 2013 because of primary or secondary liver malignancies
      (colorectal cancer [n = 195, 38.8%], neuroendocrine tumors [n = 77, 15.3%],
      breast cancer [n = 68, 13.5%], hepatocellular carcinoma [n = 59, 11.8%],
      cholangiocellular carcinoma [n = 40, 8.0%], or urologic tumors [n = 14, 2.8%]).
      Manually drawn regions of interest around tumors and adjacent healthy liver
      tissue for up to 3 lesions per patient on (99m)Tc-MAA and (90)Y-bremsstrahlung
      scans were used to quantify mean counts per pixel and evaluate the mean tumor-to
      background ratio (TBR). Data were given as mean +/- SD. Additionally, uptake in
      lesions on (99m)Tc-MAA and (90)Y-bremsstrahlung scans was graded visually as
      homogeneously higher than (grade 1), heterogeneously higher than (grade 2), equal
      to (grade 3), or lower than (grade 4) uptake in normal liver tissue. The Mann
      Whitney U test and Spearman correlation were used to evaluate statistically
      significant differences between (99m)Tc-MAA and (90)Y-bremsstrahlung SPECT.
      RESULTS: In total, 1,008 lesions were analyzed. Of the 23% (230/1,008) of lesions
      that had grade 1 uptake on (99m)Tc-MAA SPECT, 81% (186/230) remained grade 1
      after radioembolization whereas 16% (37/230) were grade 2. Of the lesions with
      grade 2 uptake on (99m)Tc-MAA SPECT, 16% had grade 1 uptake and 82% grade 2
      uptake after radioembolization. Of the lesions with grade 3 uptake, however, 27%
      had grade 1 uptake and 47% grade 2 uptake after radioembolization. Even among the
      lesions with grade 4 uptake on (99m)Tc-MAA SPECT, 21% had grade 1 uptake and 46%
      grade 2 uptake after radioembolization. The mean TBR on (99m)Tc-MAA and (90)Y
      bremsstrahlung SPECT showed a significant, though low, correlation in the total
      population (r = 0.26; P < 0.001) and in hepatocellular carcinoma (r = 0.4; P <
      0.001), cholangiocellular carcinoma (r = 0.3; P < 0.05), breast cancer (r = 0.3;
      P < 0.001), colorectal cancer (r = 0.2; P < 0.001), and neuroendocrine tumors (r
      = 0.2; P < 0.01). CONCLUSION: Although significant for most lesions, the
      correlation between (99m)Tc-MAA and (90)Y-microsphere mean TBR was low.
      Classifying uptake into 4 grades revealed that lesions with high uptake on
      (99m)Tc-MAA SPECT maintain high uptake within radioembolization. More than 60% of
      lesions with a pretherapeutically lower uptake than in healthy liver tissue,
      however, showed high uptake within radioembolization. Patients with low tumor
      uptake on pretherapeutic (99m)Tc-MAA imaging should not be excluded from
      radioembolization.

PMID- 26315831
TI  - Myocardial Blood Flow and Innervation Measures from a Single Scan: An Appealing
      Concept but a Challenging Paradigm.

PMID- 26315832
TI  - Analytic Validation of the Automated Bone Scan Index as an Imaging Biomarker to
      Standardize Quantitative Changes in Bone Scans of Patients with Metastatic
      Prostate Cancer.
AB  - A reproducible and quantitative imaging biomarker is needed to standardize the
      evaluation of changes in bone scans of prostate cancer patients with skeletal
      metastasis. We performed a series of analytic validation studies to evaluate the
      performance of the automated bone scan index (BSI) as an imaging biomarker in
      patients with metastatic prostate cancer. METHODS: Three separate analytic
      studies were performed to evaluate the accuracy, precision, and reproducibility
      of the automated BSI. Simulation study: bone scan simulations with predefined
      tumor burdens were created to assess accuracy and precision. Fifty bone scans
      were simulated with a tumor burden ranging from low to high disease confluence
      (0.10-13.0 BSI). A second group of 50 scans was divided into 5 subgroups, each
      containing 10 simulated bone scans, corresponding to BSI values of 0.5, 1.0, 3.0,
      5.0, and 10.0. Repeat bone scan study: to assess the reproducibility in a routine
      clinical setting, 2 repeat bone scans were obtained from metastatic prostate
      cancer patients after a single 600-MBq (99m)Tc-methylene diphosphonate injection.
      Follow-up bone scan study: 2 follow-up bone scans of metastatic prostate cancer
      patients were analyzed to determine the interobserver variability between the
      automated BSIs and the visual interpretations in assessing changes. The automated
      BSI was generated using the upgraded EXINI bone(BSI) software (version 2). The
      results were evaluated using linear regression, Pearson correlation, Cohen kappa
      measurement, coefficient of variation, and SD. RESULTS: Linearity of the
      automated BSI interpretations in the range of 0.10-13.0 was confirmed, and
      Pearson correlation was observed at 0.995 (n = 50; 95% confidence interval, 0.99
      0.99; P < 0.0001). The mean coefficient of variation was less than 20%. The mean
      BSI difference between the 2 repeat bone scans of 35 patients was 0.05 (SD =
      0.15), with an upper confidence limit of 0.30. The interobserver agreement in the
      automated BSI interpretations was more consistent (kappa = 0.96, P < 0.0001) than
      the qualitative visual assessment of the changes (kappa = 0.70, P < 0.0001) was
      in the bone scans of 173 patients. CONCLUSION: The automated BSI provides a
      consistent imaging biomarker capable of standardizing quantitative changes in the
      bone scans of patients with metastatic prostate cancer.

PMID- 26315833
TI  - SPECT Myocardial Perfusion Imaging: Poststress, End Systolic Images and the
      Ongoing Effort to Improve Diagnostic Accuracy.

PMID- 26315835
TI  - Mapping Radiation Injury and Recovery in Bone Marrow Using 18F-FLT PET/CT and
      USPIO MRI in a Rat Model.
AB  - We present and test the use of multimodality imaging as a topological tool to map
      the amount of the body exposed to ionizing radiation and the location of
      exposure, which are important indicators of survival and recovery. To achieve our
      goal, PET/CT imaging with 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) was used
      to measure cellular proliferation in bone marrow (BM), whereas MRI using ultra
      small superparamagnetic iron oxide (USPIO) particles provided noninvasive
      information on radiation-induced vascular damage. METHODS: Animals were x-ray
      irradiated at a dose of 7.5 Gy with 1 of 3 radiation schemes-whole-body
      irradiation, half-body shielding (HBS), or 1-leg shielding (1LS)-and imaged
      repeatedly. The spatial information from the CT scan was used to segment the
      region corresponding to BM from the PET scan using algorithms developed in-house,
      allowing for quantification of proliferating cells, and BM blood volume was
      estimated by measuring the changes in the T2 relaxation rates (DeltaR2) collected
      from MR scans. RESULTS: (18)F-FLT PET/CT imaging differentiated irradiated from
      unirradiated BM regions. Two days after irradiation, proliferation of 1LS animals
      was significantly lower than sham (P = 0.0001, femurs; P < 0.0001, tibias) and
      returned to sham levels by day 10 (P = 0.6344, femurs; P = 0.3962, tibias). The
      degree of shielding affected proliferation recovery, showing an increase in the
      irradiated BM of the femurs, but not the tibias, of HBS animals when compared
      with 1LS (P = 0.0310, femurs; P = 0.5832, tibias). MRI of irradiated spines
      detected radiation-induced BM vascular damage, measured by the significant
      increase in DeltaR2 2 d after whole-body irradiation (P = 0.0022) and HBS (P =
      0.0003) with a decreasing trend of values, returning to levels close to baseline
      over 10 d. Our data were corroborated using gamma-counting and histopathology.
      CONCLUSION: We demonstrated that (18)F-FLT PET/CT and USPIO MRI are valuable
      tools in mapping regional radiation exposure and the effects of radiation on BM.
      Analysis of the (18)F-FLT signal allowed for a clear demarcation of exposed BM
      regions and elucidated the kinetics of BM recovery, whereas USPIO MRI was used to
      assess vascular damage and recovery.

PMID- 26315834
TI  - Photoacoustic Tomography Detects Early Vessel Regression and Normalization During
      Ovarian Tumor Response to the Antiangiogenic Therapy Trebananib.
AB  - The primary aim of this study was to assess the potential of in vivo
      photoacoustic tomography for direct functional measurement of ovarian tumor
      response to antiangiogenic therapy. METHODS: In vivo studies were performed with
      institutional animal care and use committee approval. We used an orthotopic mouse
      model of ovarian cancer treated with trebananib (n = 9) or vehicle (n = 9). Tumor
      bearing mice were randomized into trebananib or vehicle groups at day 10 and
      dosed on days 12, 15, and 18 after implantation. Photoacoustic tomography and
      blood draws were performed at day 10 and then 24 h after each drug dose. Tumors
      were excised for histopathology after the final studies on day 19. Data analysis
      to test for statistical significance was performed blinded. RESULTS: Blockade of
      angiopoietin signaling using trebananib resulted in reduced total hemoglobin
      weighted photoacoustic signal (n = 9, P = 0.01) and increased oxyhemoglobin
      weighted photoacoustic signal (n = 9, P < 0.01). The latter observation indicated
      normalization of the residual tumor vessels, which was also implied by low levels
      of angiopoietin 1 in serum biomarker profiling (0.76 +/- 0.12 ng/mL). These
      noninvasive measures reflected a 30% reduction in microvessel density and
      increased vessel maturation in ex vivo sections. CONCLUSION: Photoacoustic
      tomography is able to evaluate both vessel regression and normalization in
      response to trebananib. Noninvasive imaging data were supported by modulation of
      serum markers in vitro and ex vivo histopathology.

PMID- 26315836
TI  - 18F-Labeled Single-Stranded DNA Aptamer for PET Imaging of Protein Tyrosine
      Kinase-7 Expression.
AB  - Protein tyrosine kinase-7 (PTK7), a member of receptor tyrosine kinase
      superfamily initially identified as colon carcinoma kinase-4, is highly expressed
      in various human malignancies. Its expression was found to correlate with
      aggressive biologic behaviors such as increased cell proliferation, invasiveness,
      and migration. Despite the importance and unmet need of imaging PTK7 in vivo,
      there is currently no clinically relevant method to visualize tumoral PTK7
      expression noninvasively such as PET or SPECT. This study aimed to develop a
      specific, selective, and high-affinity PET radioligand based on single-stranded
      DNA aptamer to address this challenge. METHODS: Sgc8, a 41-oligonucleotide that
      targets to PTK7, was labeled with (18)F using a 2-step radiochemical synthesis,
      which featured a direct 1-step radiofluorination on the distinctive spirocyclic
      hypervalent iodine(III) precursor to give (18)F-fluorobenzyl azide followed by
      copper-mediated click conjugation with Sgc8-alkyne. (18)F-Sgc8 was evaluated in
      vitro and in vivo in 2 cell lines, HCT116 and U87MG, which express high and low
      amounts of PTK7, respectively. RESULTS: Sgc8 was labeled efficiently with (18)F
      in an isolated radiochemical yield of 62% +/- 2%, non-decay-corrected based on
      (18)F-fluorobenzyl azide. (18)F-Tr-Sgc8 was found to possess high-affinity
      binding to both cell lines, with binding affinity values of 2.7 +/- 0.6 nM for
      HCT116 and 16.9 +/- 2.1 nM for U87MG. In vivo PET imaging clearly visualized PTK7
      expression in HCT116 xenografted mice, with tumor uptake of 0.76 +/- 0.09
      percentage injected dose per gram (%ID/g) at 30 min after injection for the
      subcutaneous tumor model and greater than 1.5 %ID/g for the liver metastasis
      model. U87MG xenograft tumors had much lower tracer accumulation (0.13 +/- 0.06
      %ID/g at 30 min after injection), which was consistent with the lower expression
      of PTK7 in this tumor model. The labeled aptamer was rapidly cleared from the
      blood through the kidneys and bladder to give high tumor-to-blood and tumor-to
      muscle ratios of 7.29 +/- 1.51 and 10.25 +/- 2.08, respectively. CONCLUSION: The
      (18)F-radiolabeling methodology shown here is a robust procedure for labeling
      aptamers and similar chemical moieties and can be applied to many different
      targets. Quantification of PTK7 using (18)F-Tr-Sgc8 may be suitable for clinical
      translation and might help in the future to select and monitor appropriate
      therapies.

PMID- 26315837
TI  - Isoliquiritigenin Inhibits Interferon-gamma-Inducible Genes Expression in
      Hepatocytes through Down-Regulating Activation of JAK1/STAT1, IRF3/MyD88,
      ERK/MAPK, JNK/MAPK and PI3K/Akt Signaling Pathways.
AB  - BACKGROUND & AIMS: The high expression levels of interferon-gamma (IFN-gamma)
      inducible genes correlate positively with liver diseases. The present study aimed
      to explore the effect of isoliquiritigenin (ISL) on the expression of genes
      induced by IFN-gamma in vitro, and to elucidate the underlying molecular
      mechanisms. METHODS: HepG2 and L02 cells were divided into control, ISL, IFN
      gamma, and IFN-gamma plus ISL groups. The cytotoxicity of compounds to cells was
      evaluated by Cell Counting Kit 8 (CCK8) assay; the expression levels of chemokine
      (C-X-C motif) ligand 9 (CXCL9), CXCL10, CXCL11, and interleukin-6 (IL-6) in cells
      and supernatant were measured by quantitative real time polymerase chain reaction
      (qRT-PCR) and ELISA, respectively. Moreover, western blot was used to examine the
      phosphorylated levels of janus kinase (JAK)/signal transducer and activator of
      transcription 1 (STAT1), nuclear factor (NF)-kappaB, interferon regulatory factor
      3 (IRF3)/myeloid differentiation factor 88 (MyD88), mitogen-activated protein
      kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/Protein Kinase B (Akt) in
      HepG2 and L02 cells exposed to ISL, IFN-gamma and IFN-gamma plus ISL. RESULTS:
      The results showed that IFN-gamma treatment induced the expression of CXCL9,
      CXCL10, CXCL11, and IL-6 in HepG2 and LO2 cells, which could be significantly and
      dose-dependently inhibited by ISL treatment (P < 0.05 or P < 0.01), but the
      inhibitory effect of ISL on IL-6 expression was not so good as on CXCL9, CXCL10,
      and CXCL11 expression. Furthermore, ISL treatment dose-dependently inhibited the
      activation of JAK1/STAT1, IRF3/MyD88, extracellular signal-regulated kinase
      (ERK)/MAPK, c-Jun N-terminal kinase (JNK)/MAPK, and PI3K/Akt signaling pathways
      (P < 0.05), but had no effect on the activation of JAK2/STAT1, NF-kappaB and
      p38/MAPK signaling pathways. CONCLUSION: We demonstrate that ISL inhibits IFN
      gamma-induced inflammation in hepatocytes via influencing the activation of
      JAK1/STAT1, IRF3/MyD88, ERK/MAPK, JNK/MAPK, and PI3K/Akt signaling pathways.

PMID- 26315838
TI  - Susceptibility-weighted magnetic resonance imaging for the evaluation of deep
      infiltrating endometriosis: preliminary results.
AB  - BACKGROUND: Knowledge of the precise sites of deep infiltrating endometriosis
      (DIE) lesions is essential for preoperative workup and treatment. Susceptibility
      weighted imaging (SWI) has high sensitivity for blood products and have recently
      been applied in abdominal imaging. PURPOSE: To determine the value of SWI in the
      diagnosis of DIE. MATERIAL AND METHODS: Forty-three clinically suspected DIE
      patients with sonographically diagnosed ovarian endometriomas who had tenderness
      or palpable nodule(s) on rectovaginal examination were referred to pelvic
      magnetic resonance imaging (MRI) including SWI. Two patients were excluded from
      the study because of low quality of SWI series. Twenty-eight patients who were
      offered laparoscopic endometriosis surgery (LES) preferred medical treatment over
      surgical approach. Thirteen out of 41 participants had LES. Lesions were
      evaluated for their locations, signal intensities on T1-weighted (T1W) and T2
      weighted (T2W) images, and presence of signal voids on SWI using 3T MRI and
      correlated with LES findings. RESULTS: A total of 18 endometriosis foci were
      laparoscopically removed from 13 patients. DIE lesions removed at laparoscopy
      were located at the uterosacral ligament (9/18), rectovaginal region (4/18),
      retrocervical region (2/18), and fallopian tubes (3/18). Eleven out of 18 (61%)
      DIE foci were detected by their high-signal intensities on T1W images whereas 16
      out of 18 (89%) DIE foci were detected by signal voids on SWI. CONCLUSION: SWI
      imaging with its high sensitivity to blood products, contributes to the diagnosis
      of DIE by depicting different phases of hemorrhage not seen by conventional MRI
      sequences.

PMID- 26315839
TI  - Sclerosing Lipogranuloma with Multiple Skin Lesions and Pulmonary Involvement,
      Secondary to a Factitious Disorder.

PMID- 26315840
TI  - What accounts for ethnic differences in newborn skinfold thickness comparing
      South Asians and White Caucasians? Findings from the START and FAMILY Birth
      Cohorts.
AB  - OBJECTIVE: South Asians are a high-risk group for type 2 diabetes and coronary
      heart disease. We sought to determine ethnic differences in newborn adiposity
      comparing South Asians (SA) to White Caucasians (Whites). METHODS: Seven hundred
      ninety pregnant women (401 SA, 389 Whites) and their full-term offspring from two
      birth cohorts in Canada were analyzed. Pregnant women completed a health
      assessment including a 75-g oral glucose tolerance test to assess for
      dysglycemia. Birthweight, length, waist and hip circumference, and triceps and
      subscapular skinfold thickness (a surrogate measure of body adiposity) were
      measured in all newborns. Multivariate regression was used to identify maternal
      factors associated with newborn skinfold measurements. RESULTS: South Asian women
      were younger (30.1 vs 31.8 years, P<0.001), their prepregnancy body mass index
      was lower (23.7 vs 26.2, P<0.0001) and gestational diabetes was substantially
      higher (21% vs 13%, P=0.005) compared with Whites. Among full-term newborns,
      South Asians had lower birthweight (3283 vs 3517 g, P=0.0001), had greater
      skinfold thickness (11.7 vs 10.6 mm; P=0.0001) and higher waist circumference
      (31.1 vs 29.9 cm, P=0.0001) compared with Whites. Risk factors for newborn
      skinfold thickness included South Asian ethnicity (standardized estimate (s.e.):
      0.24; P<0.0001), maternal glucose (s.e.: 0.079; P=0.04) and maternal body fat
      (s.e.: 0.14; P=0.0002). CONCLUSIONS: South Asian newborns are lower birthweight
      and have greater skinfold thickness, compared with White newborns, and this is
      influenced by maternal body fat and glucose. Interventions aimed at reducing body
      fat prior to pregnancy and gestational diabetes during pregnancy in South Asians
      may favorably alter newborn body composition and require evaluation.

PMID- 26315841
TI  - Exogenous administration of DLK1 ameliorates hepatic steatosis and regulates
      gluconeogenesis via activation of AMPK.
AB  - BACKGROUND/OBJECTIVES: Activation of Notch signaling pathologically enhances
      lipogenesis and gluconeogenesis in the liver causing non-alcoholic fatty liver
      disease (NAFLD) and diabetes. Delta-like 1 homolog (DLK1), an imprinted gene that
      can modulate adipogenesis and muscle development in mice, was found as an
      inhibitory regulator of Notch signaling. Therefore, we investigated the metabolic
      effect of exogenous DLK1 in vitro and in vivo. SUBJECTS/METHODS: A soluble DLK1
      peptide was generated with fusion between a human Fc fragment and extracellular
      domain of DLK1. Male db/db mice were randomly assigned to two groups: vehicle
      treated and DLK1-treated group (25 mg kg(-1), intraperitoneal injection, twice a
      week for 4 weeks). Primary mice hepatocytes and HepG2 cells were used for in
      vitro experiments. RESULTS: After 4 weeks of DLK1 administration, hepatic
      triglyceride content and lipid droplets in liver tissues, as well as serum levels
      of liver enzymes, were markedly decreased in db/db mice. DLK1 treatment induced
      phosphorylation of AMPK and ACC and suppressed nuclear expression of SREBP-1c in
      the mouse liver or hepatocytes, indicating regulation of fatty acid oxidation and
      synthesis pathways. Furthermore, DLK1-treated mice showed significantly lower
      levels of fasting and random glucose, with improved glucose and insulin tolerance
      compared with the vehicle-treated group. Macrophage infiltration and
      proinflammatory cytokine levels in the epididymal fat were decreased in DLK1
      treated db/db mice. Moreover, DLK1 suppressed glucose production from
      hepatocytes, which was blocked after co-administration of an AMPK inhibitor,
      compound C. DLK1-treated hepatocytes and mouse liver tissues showed lower PEPCK
      and G6Pase expression. DLK1 triggered AKT phosphorylation followed by cytosolic
      translocation of FOXO1 from the nucleus in hepatocytes. CONCLUSIONS: The present
      study demonstrated that exogenous administration of DLK1 reduced hepatic
      steatosis and hyperglycemia via AMPK activation in the liver. This result
      suggests that DLK1 may be a novel therapeutic approach for treating NAFLD and
      diabetes.

PMID- 26315842
TI  - Intestinal GLP-1 and satiation: from man to rodents and back.
AB  - In response to luminal food stimuli during meals, enteroendocrine cells release
      gastrointestinal (GI) peptides that have long been known to control secretory and
      motor functions of the gut, pancreas and liver. Glucagon-like peptide-1 (GLP-1)
      has emerged as one of the most important GI peptides because of a combination of
      functions not previously ascribed to any other molecule. GLP-1 potentiates
      glucose-induced insulin secretion, suppresses glucagon release, slows gastric
      emptying and may serve as a satiation signal, although the physiological status
      of the latter function has not been fully established yet. Here we review the
      available evidence for intestinal GLP-1 to fulfill a number of established
      empirical criteria for assessing whether a hormone inhibits eating by eliciting
      physiological satiation in man and rodents. 

PMID- 26315843
TI  - Changes in inflammation, oxidative stress and adipokines following bariatric
      surgery among adolescents with severe obesity.
AB  - BACKGROUND/OBJECTIVES: Inflammation, oxidative stress and dysregulation of
      adipokines are thought to be pathophysiological mechanisms linking obesity to the
      development of insulin resistance and atherosclerosis. In adults, bariatric
      surgery reduces inflammation and oxidative stress, and beneficially changes the
      levels of several adipokines, but little is known about the postsurgical changes
      among adolescents. SUBJECTS/METHODS: In two separate longitudinal cohorts we
      evaluated change from baseline of interleukin-6 (IL-6), tumor necrosis factor
      alpha (TNF-alpha), monocyte chemo-attractant protein-1 (MCP-1), oxidized low
      density lipoprotein cholesterol (oxLDL), adiponectin, leptin and resistin up to
      12 months following elective laparoscopic Roux-en-Y gastric bypass (RYGB) or
      vertical sleeve gastrectomy (VSG) surgery in adolescents with severe obesity.
      RESULTS: In cohort 1, which consisted of 39 adolescents (mean age 16.5+/-1.6
      years; 29 females) undergoing either RYGB or VSG, IL-6 (baseline: 2.3+/-3.4 pg
      ml(-1) vs 12 months: 0.8+/-0.6 pg ml(-1), P<0.01), leptin (baseline: 178+/-224 ng
      ml(-1) vs 12 months: 41.4+/-31.9 ng ml(-1), P<0.001) and oxLDL (baseline: 41.6+/
      11.6 U l(-1) vs 12 months: 35.5+/-11.1 U l(-1), P=0.001) significantly decreased
      and adiponectin significantly increased (baseline: 5.4+/-2.4 MUg ml(-1) vs 12
      months: 13.5+/-8.9 MUg ml(-1), P<0.001). In cohort 2, which consisted of 13
      adolescents (mean age 16.5+/-1.6 years; 10 females) undergoing RYGB, results were
      similar: IL-6 (baseline: 1.7+/-0.9 pg ml(-1) vs 12 months: 0.4+/-0.9 pg ml(-1),
      P<0.05) and leptin (baseline: 92.9+/-31.3 ng ml(-1) vs 12 months: 37.3+/-33.4 ng
      ml(-1), P<0.001) significantly decreased and adiponectin significantly increased
      (baseline: 6.1+/-2.9 MUg ml(-1) vs 12 months: 15.4+/-8.0 MUg ml(-1), P<0.001).
      When the cohorts were combined to evaluate changes at 12 months, oxLDL also
      significantly decreased (baseline: 39.8+/-16.7 U l(-1) vs 12 months: 32.7+/-11.9
      U l(-1), P=0.03). CONCLUSIONS: Bariatric surgery produced robust improvements in
      markers of inflammation, oxidative stress and several adipokines among
      adolescents with severe obesity, suggesting potential reductions in risk for type
      2 diabetes and cardiovascular disease.

PMID- 26315844
TI  - Intensive lifestyle treatment for non-alcoholic fatty liver disease in children
      with severe obesity: inpatient versus ambulatory treatment.
AB  - BACKGROUND/AIMS: Lifestyle intervention is the only established therapy for non
      alcoholic fatty liver disease (NAFLD). The optimal treatment schedule and
      predictors of response of this treatment have not been established in children.
      We aimed to evaluate the 2-year efficacy of an inpatient versus ambulatory
      intensive lifestyle intervention for treating NAFLD in children with severe
      obesity. METHODS: A cohort study of 51 severely obese non-diabetic children (mean
      age 14.7 (+/-2.4) years; BMI-z-score 3.5 (+/-0.5)) with liver steatosis were non
      randomly allocated to inpatient treatment (2 or 6 months), ambulatory treatment
      or usual care. Proton Magnetic Resonance Spectroscopy determined liver steatosis
      and serum alanine aminotransferase (ALT) at 6 months were the primary outcome
      measures. Baseline variables were evaluated as predictors of treatment response.
      RESULTS: Liver steatosis had disappeared in 43, 29 and 22% and serum ALT
      normalized in 41, 33 and 6% at the end of 6 months in the inpatient, ambulatory
      or usual care treatment groups, respectively. Only the proportions of ALT
      normalization in inpatient and ambulatory treatment compared with usual care were
      significantly higher. Treatment effects of inpatient and ambulatory treatment
      were sustained at 1.5 years follow-up. No baseline characteristic, including
      PNPLA3 polymorphism or leptin, was consistently predictive for treatment
      response. CONCLUSIONS: A 6-month intensive inpatient and ambulatory lifestyle
      treatment in children with severe obesity reverses NAFLD in a minority of
      patients. This study suggests that inpatient compared with ambulatory intensive
      treatment does not importantly increase treatment success. Further efforts to
      optimize and individualize lifestyle interventions and additional treatments
      options are needed particular for children with severe obesity resistant to
      conventional lifestyle interventions.

PMID- 26315845
TI  - Early prophylaxis in children with severe haemophilia A: clinical and ultrasound
      imaging outcomes.
AB  - AIM: This observational study was undertaken with the aim to describe the
      characteristics and evaluate the outcomes of prophylactic treatment in children
      with severe haemophilia A (HA) treated at our centre. METHODS: Twenty-five
      patients aged 4-19 years with severe HA, no history of inhibitors and treated
      with at least two infusions of factor VIII (FVIII) per week were studied.
      Prophylactic doses and annual joint bleeding rate (AJBR) were retrospectively
      evaluated over the last 5 years. Current joint status was assessed using the
      Haemophilia Joint Health Score (HJHS) (136 joints of 23 patients) and the
      Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) procedure (124
      joints of 21 patients). RESULTS: Median AJBR was 0.2 and median prophylaxis dose
      65.4 IU-1  kg-1  week-1 . Median total HJHS was 0 (range 0-13) and total HEAD-US
      1 (0-8). At the joint level, 85.3% of joints were normal on HJHS and 79.0% on US.
      The ankle was the joint most commonly affected, considering bleeding and
      ultrasound results. Correlation was found between HEAD-US scores and bleeding
      scores but not between HEAD-US and HJHS scores. HJHS and HEAD-US scores were
      concordant in 91/124 (73.4%) joints (86 joints normal and five abnormal).
      Ultrasound detected minimal changes in 19.6% of joints with normal physical
      function, whereas 12.2% of joints considered normal on ultrasound showed changes
      at HJHS. CONCLUSION: A well-preserved joint status was found in our cohort. High
      resolution US detected a higher percentage of abnormalities than the physical
      evaluation, but the clinical implications of these findings still need to be
      ascertained.

PMID- 26315847
TI  - Photoinduced cytotoxicity by a platinum diimine complex employing magnetite
      silica nanocomposites as delivery vehicles.
AB  - Tartaric acid-modified core-shell magnetite-silica nanocomposites were prepared
      by a sol-gel method, and characterized by X-ray diffraction, Fourier transform
      infrared spectroscopy, transmission electron microscopy and dynamic light
      scattering. Then the nanocomposites were employed as carriers of a photoactive
      platinum diimine complex. Photoinduced cytotoxicity by the photosensitizer-loaded
      nanocomposites in different human carcinoma cells has been studied by cell
      viability assay. The results suggest that the as-synthesized nanocomposites have
      good stability in water, and the cytotoxicity induced by the platinum diimine
      complex in red light can be significantly enhanced when the photosensitizer is
      loaded with the magnetic nanocomposites. 

PMID- 26315848
TI  - Bacteriophage-based nanoprobes for rapid bacteria separation.
AB  - The lack of practical methods for bacterial separation remains a hindrance for
      the low-cost and successful development of rapid detection methods from complex
      samples. Antibody-tagged magnetic particles are commonly used to pull analytes
      from a liquid sample. While this method is well-established, improvements in
      capture efficiencies would result in an increase of the overall detection assay
      performance. Bacteriophages represent a low-cost and more consistent
      biorecognition element as compared to antibodies. We have developed nanoscale
      bacteriophage-tagged magnetic probes, where T7 bacteriophages were bound to
      magnetic nanoparticles. The nanoprobe allowed the specific recognition and
      attachment to E. coli cells. The phage magnetic nanprobes were directly compared
      to antibody-conjugated magnetic nanoprobes. The capture efficiencies of
      bacteriophages and antibodies on nanoparticles for the separation of E. coli K12
      at varying concentrations were determined. The results indicated a similar
      bacteria capture efficiency between the two nanoprobes. 

PMID- 26315846
TI  - Mitochondrial disease: genetics and management.
AB  - Mitochondrial disease is one of the most common groups of genetic diseases with a
      minimum prevalence of greater than 1 in 5000 in adults. Whilst multi-system
      involvement is often evident, neurological manifestation is the principal
      presentation in most cases. The multiple clinical phenotypes and the involvement
      of both the mitochondrial and nuclear genome make mitochondrial disease
      particularly challenging for the clinician. In this review article we cover
      mitochondrial genetics and common neurological presentations associated with
      adult mitochondrial disease. In addition, specific and supportive treatments are
      discussed.

PMID- 26315849
TI  - Total Synthesis of (-)-Conolutinine.
AB  - The first enantioselective synthesis of (-)-conolutinine was achieved in 10
      steps. The synthesis featured a catalytic asymmetric bromocyclization of
      tryptamine to forge the tricycle intermediate. Hydration of an alkene catalyzed
      by Co(acac)2 was also employed as a key step to diastereoselectively introduce
      the tertiary alcohol moiety. The absolute configuration of (-)-conolutinine was
      established to be (2S,5aS,8aS,13aR) based on this asymmetric total synthesis. 

PMID- 26315850
TI  - Establishing the Structural Integrity of Core-Shell Nanoparticles against
      Elemental Migration using Luminescent Lanthanide Probes.
AB  - Core-shell structured nanoparticles are increasingly used to host luminescent
      lanthanide ions but the structural integrity of these nanoparticles still lacks
      sufficient understanding. Herein, we present a new approach to detect the
      diffusion of dopant ions in core-shell nanostructures using luminescent
      lanthanide probes whose emission profile and luminescence lifetime are sensitive
      to the chemical environment. We show that dopant ions in solution-synthesized
      core-shell nanoparticles are firmly confined in the designed locations. However,
      annealing at certain temperatures (greater than circa 350  degrees C) promotes
      diffusion of the dopant ions and leads to degradation of the integrity of the
      nanoparticles. These insights into core-shell nanostructures should enhance our
      ability to understand and use lanthanide-doped luminescent nanoparticles. 

PMID- 26315852
TI  - Nonlinearities in protein space limit the utility of informatics in protein
      biophysics.
AB  - We examine the utility of informatic-based methods in computational protein
      biophysics. To do so, we use newly developed metric functions to define
      completely independent sequence and structure spaces for a large database of
      proteins. By investigating the relationship between these spaces, we demonstrate
      quantitatively the limits of knowledge-based correlation between the sequences
      and structures of proteins. It is shown that there are well-defined, nonlinear
      regions of protein space in which dissimilar structures map onto similar
      sequences (the conformational switch), and dissimilar sequences map onto similar
      structures (remote homology). These nonlinearities are shown to be quite common
      almost half the proteins in our database fall into one or the other of these two
      regions. They are not anomalies, but rather intrinsic properties of structural
      encoding in amino acid sequences. It follows that extreme care must be exercised
      in using bioinformatic data as a basis for computational structure prediction.
      The implications of these results for protein evolution are examined.

PMID- 26315853
TI  - Hepatitis B and D viral receptors.

PMID- 26315851
TI  - Within-Day Variability of Fatigue and Pain Among African Americans and Non
      Hispanic Whites With Osteoarthritis of the Knee.
AB  - OBJECTIVE: Fatigue is common among persons with osteoarthritis (OA), but little
      is known about racial/ethnic differences in the prevalence, correlates, or
      dynamics of fatigue in OA. This research therefore used experience sampling
      methodology (ESM) to examine fatigue and pain at global and momentary levels
      among African Americans and non-Hispanic whites with OA. METHODS: Thirty-nine
      African Americans and 81 non-Hispanic whites with physician-diagnosed knee OA
      completed a baseline interview and an ESM protocol assessing fatigue, pain, and
      mood 4 times daily for 7 days. In addition to analyzing basic group differences,
      multilevel modeling examined within- versus between-subject patterns and
      correlates of variability in momentary fatigue, controlling for demographics and
      other potential confounders. RESULTS: Both racial groups experienced moderate
      levels of fatigue; however, there were clear individual differences in both mean
      fatigue level and variability across momentary assessments. Mean fatigue levels
      were associated with global pain and depression. Increase in fatigue over the
      course of the day was much stronger among non-Hispanic whites than African
      Americans. Momentary fatigue and pain were closely correlated. Mean fatigue
      predicted variability in mood; at the momentary level, both fatigue and pain were
      independently associated with mood. CONCLUSION: Fatigue is a significant factor
      for both African Americans and non-Hispanic whites with OA, and is negatively
      related to quality of life. Pain symptoms, at both the momentary level and across
      individuals, were robust predictors of fatigue. Although overall levels of
      reported symptoms were similar across these 2 groups, the pattern of fatigue
      symptoms across the day differed.

PMID- 26315854
TI  - New Evidence about the Spontaneous Symmetry Breaking: Action of an Asymmetric
      Weak Heat Source.
AB  - In the present study, we show how, in a stagnant water solution of uncharged
      aggregated achiral porphyrin-based molecules, a mirror-symmetry breaking (SB) can
      be induced and controlled by means of a weak asymmetric thermal gradient. In
      particular, it is shown that the optical activity of the aggregate porphyrin
      solution can be generated and reversed, in sign, only acting on the thermal ramp
      direction (heating or cooling). In order to avoid data misinterpretation, the
      aggregate structure modifications with the temperature change and the linear
      dichroism contribution to circular dichroism spectra were evaluated. A model
      simulation, using a finite element analysis approach describing the thermal
      flows, shows that small thermal gradients are able to give rise to asymmetric
      heat flow. The results reported here can be considered new evidence about the
      spontaneous symmetry breaking phenomenon induced by very weak forces having an
      important role in the natural chiral selective processes. 

PMID- 26315855
TI  - Traumatic brain injury accelerates kindling epileptogenesis in rats.
AB  - OBJECTIVES: Traumatic brain injury (TBI) is a well-known cause of symptomatic
      epilepsy. In animal models of post-traumatic epilepsy (PTE), progression of
      trauma to epilepsy takes several weeks to months. Although this long process is
      similar to clinical PTE, it is costly and laborious. We used a combination of TBI
      and kindling as an accelerated animal model to develop epilepsy in much shorter
      period compared to that occurring in PTE. METHODS: Traumatic brain injury was
      exerted to parieto-temporal cortex of anaesthetised rats by controlled cortical
      impact (CCI, 5 mm round tip, 4.5 mm/seconds velocity and 150 ms duration).
      Chemical kindling started 24 hours after CCI by intraperitoneal injection of 30
      mg/kg pentylenetetrazole (PTZ) every other day until manifestation of three
      consecutive generalised seizures. Rapid electrical kindling of the amygdala began
      1 week after TBI by exertion of 12 daily threshold stimuli (50 Hz mono-phasic
      square-wave stimulus of 1 ms per wave for 3 seconds) with 5 minutes interval
      between each stimulation until the rats became kindled. RESULTS: Controlled
      cortical impact injury accelerated rate of both chemical and electrical kindling.
      Number of PTZ injections required for acquisition of generalised seizures
      decreased from 13.1 +/- 1.6 in sham-operated animals to 7.1 +/- 0.3 in traumatic
      rats (p < 0.05). The required number of stimuli to elicit electrically kindled
      focal and generalised seizures decreased from 24.0 +/- 3.9 and 80 +/- 6.5 in sham
      operated animals to 6.6 +/- 0.9 and 53 +/- 6.5 in traumatic rats (p < 0.01),
      respectively. LIMITATIONS: Unlike the animal models of PTE in which recurrent
      seizures occur spontaneously after TBI, in our study, epilepsy is elicited by
      kindling stimulations. DISCUSSION: Traumatic brain injury facilitates acquisition
      of epilepsy in both chemical and electrical kindling models. Combination of
      trauma and kindling can be considered as an inexpensive and time-saving animal
      model in PTE studies.

PMID- 26315857
TI  - Recruitment and Reasons for Non-Participation in a Family-Coping-Orientated
      Palliative Home Care Trial (FamCope).
AB  - Cancer patients and their family caregivers need support to cope with physical,
      psychosocial, and existential problems early in the palliative care trajectory.
      Many interventions target patient symptomatology, with health care professionals
      acting as problem-solvers. Family coping, however, is a new research area within
      palliative care. The FamCope intervention was developed to test if a nurse-led
      family-coping-orientated palliative home care intervention would help families
      cope with physical and psychosocial problems at home--together as a family and in
      interaction with health care professionals. However, an unexpectedly high number
      of families declined participation in the trial. We describe and discuss the
      recruitment strategy and patient reported reasons for non-participation to add to
      the knowledge about what impedes recruitment and to identify the factors that
      influence willingness to participate in research aimed at family coping early in
      the palliative care trajectory. Patients with advanced cancer and their closest
      relative were recruited from medical, surgical, and oncological departments.
      Reasons for non-participation were registered and characteristics of participants
      and non-participants were compared to evaluate differences between subgroups of
      non-participants based on reasons not to participate and reasons to participate
      in the trial. A total of 65.9% of the families declined participation. Two main
      categories for declining participation emerged: first, that the "burden of
      illness is too great" and, second, that it was "too soon" to receive this kind of
      support. Men were more likely to participate than women. Patients in the "too
      soon" group had similar characteristics to participants in the trial. Timing of
      interventions and readiness of patients and their relatives seems to affect
      willingness to receive a family-coping-orientated care approach and impeded
      recruitment to this trial. Our findings can be used in further research and in
      clinical practice in order to construct interventions and target relevant
      populations for early family-coping-orientated palliative care.

PMID- 26315856
TI  - Cellular Signaling Pathways and Posttranslational Modifications Mediated by
      Nematode Effector Proteins.
AB  - Plant-parasitic cyst and root-knot nematodes synthesize and secrete a suite of
      effector proteins into infected host cells and tissues. These effectors are the
      major virulence determinants mediating the transformation of normal root cells
      into specialized feeding structures. Compelling evidence indicates that these
      effectors directly hijack or manipulate refined host physiological processes to
      promote the successful parasitism of host plants. Here, we provide an update on
      recent progress in elucidating the molecular functions of nematode effectors. In
      particular, we emphasize how nematode effectors modify plant cell wall structure,
      mimic the activity of host proteins, alter auxin signaling, and subvert defense
      signaling and immune responses. In addition, we discuss the emerging evidence
      suggesting that nematode effectors target and recruit various components of host
      posttranslational machinery in order to perturb the host signaling networks
      required for immunity and to regulate their own activity and subcellular
      localization. 

PMID- 26315858
TI  - Adaptations: Using Darwin's Origin to teach biology and writing.
AB  - Charles Darwin's On the Origin of Species is at once familiar and unfamiliar.
      Everyone knows that the Origin introduced the world to the idea of evolution by
      natural selection, but few of us have actually read it. We suggest that it is
      worth taking the time not only to read what Darwin had to say, but also to use
      the Origin to teach both biology and writing. It provides scientific lessons in
      areas beyond evolutionary biology, such as ecology and biogeography. In addition,
      it provides valuable rhetorical lessons-how to construct an argument, write
      persuasively, make use of evidence, know your audience, and anticipate
      counterarguments. We have been using the Origin in various classes for several
      years, introducing new generations to Darwin, in his own words. 

PMID- 26315860
TI  - Colchicine as a therapeutic option in periodic fever, aphthous stomatitis,
      pharyngitis, cervical adenitis (PFAPA) syndrome.
AB  - OBJECTIVE: To evaluate the efficacy of colchicine in reducing the frequency of
      attacks in patients with PFAPA. STUDY DESIGN: We conducted a 6-month open label,
      randomized, controlled study among patients with PFAPA who attend the Pediatric
      Rheumatology Clinic at the Rambam Medical Center in Israel. A total of 18
      patients aged4 -11 years (males:females ratio = 11:7) were randomized into a
      control group (I, 10 children) and a study group (II, 8 children). Group I was
      followed for 6 months without any intervention, and group II was initially
      followed for 3 months and was thereafter treated with colchicine for 3 additional
      months, according to standard regimen. During the 6-month period of the study the
      patients and their physician recorded all the episodes of PFAPA in a constructed
      log. DNA analyses for the 5 common FMF mutations in Israel were performed in 17
      out of the 18 patients. RESULTS: The number of episodes during the first 3 months
      was similar in both groups (group I 3.2 +/- 1.5, group II 4.9 +/- 2.3; p <=
      0.12). Group II had significantly less PFAPA attacks in the second period while
      on colchicine therapy (4.9 +/- 2.3 vs. 1.6 +/- 1.2; p <= 0.01), in opposition to
      group I, where no difference in the number of attacks was noted between the first
      and second period of follow-up (3.2 +/- 1.5 vs. 2.7 +/- 1.5; p = 0.33). Of the 17
      patients tested, 8 were carriers for FMF mutations (2 in group I and 6 in group
      II). CONCLUSION: Colchicine prophylaxis seems to be effective in reducing the
      number of attacks in PFAPA.

PMID- 26315859
TI  - Vasculitis in patients with inflammatory bowel diseases: A study of 32 patients
      and systematic review of the literature.
AB  - BACKGROUND: Published small case series suggest that inflammatory bowel disease
      [IBD; Crohn's disease (CD) or ulcerative colitis (UC)] and vasculitis co-occur
      more frequently than would be expected by chance. OBJECTIVES: To describe this
      association by an analysis of a large cohort of carefully studied patients and
      through a systematic literature review. METHODS: Patients with both IBD and
      vasculitis enrolled in the Vasculitis Clinical Research Consortium (VCRC)
      Longitudinal Studies, followed in Canadian Vasculitis research network (CanVasc)
      centers and/or in the University of Toronto's IBD clinic were included in this
      case series. A systematic literature review of patients with IBD and vasculitis
      involved a PubMed search through February 2014. The main characteristics of
      patients with Takayasu arteritis (TAK) and IBD were compared to those in patients
      with TAK without IBD followed in the VCRC. RESULTS: The study identified 32
      patients with IBD and vasculitis: 13 with large-vessel vasculitis [LVV; 12 with
      TAK, 1 with giant cell arteritis (GCA); 8 with CD, 5 with UC]; 8 with ANCA
      associated vasculitis [AAV; 6 granulomatosis with polyangiitis (GPA), 2 with
      eosinophilic granulomatosis with polyangiitis (EGPA)]; 5 with isolated cutaneous
      vasculitis; and 6 with other vasculitides. Patients with LVV and AAV were mostly
      female (18/21). The diagnosis of IBD preceded that of vasculitis in 12/13
      patients with LVV and 8/8 patients with AAV. The review of the literature
      identified 306 patients with IBD and vasculitis: 144 with LVV (133 TAK; 87 with
      IBD preceding LVV), 19 with AAV [14 GPA, 1 EGPA, 4 microscopic polyangiitis
      (MPA)], 66 with isolated cutaneous vasculitis, and 77 with other vasculitides.
      Patients with IBD and TAK were younger and had more frequent headaches,
      constitutional symptoms, or gastrointestinal symptoms compared to those patients
      in the VCRC who had TAK without IBD. CONCLUSIONS: These findings highlight the
      risk of vasculitis, especially TAK, in patients with IBD (both CD and UC).

PMID- 26315861
TI  - Editorial.

PMID- 26315862
TI  - The radiometal makes a difference. Synthesis and preliminary characterisation of
      DOTA-minigastrin analogue complexes with Ga, Lu and Y.
AB  - BACKGROUND: The minigastrin analogue - CP04: DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Met-Asp
      Phe-NH2 has been developed for CCK2R targeting. This analogue can be
      radiolabelled with 111In or 68Ga for imaging, or with 90Y and 177Lu for therapy.
      However, affinity of the chelator-peptide conjugates to the cell membrane
      receptors may vary depending on the metal incorporated into the complex. So far,
      there are no such studies for the ligands of gastrin/cholecystokinin receptor
      CCK2R. It is supposed that the reason for the differentiation of receptor
      affinity to the respective receptors is in the changes of structure of chelating
      system and their influence on the bioactive conformations of the metal conjugated
      peptides. Herein, we report on the radiolabeling of CP04 with 90Y, 177Lu and 68Ga
      and synthesis of cold CP04 complexes with respective stable metals for further
      structural and physico-chemical and biological studies. MATERIALS AND METHODS:
      From 200 to 600 MBq of 90Y, 177Lu or 68Ga were used for radiolabelling of 20 MUg
      of CP04 dissolved in ascorbic acid solution (50 mg/mL, pH 4.5). Non-radioactive
      complexes with Lu and Ga were synthesized in milligram amounts starting from 0.5
      mg up to 5 mg of CP04 dissolved in ascorbic acid solution (50 mg/mL, pH 4.5) when
      using 2-molar excess of the metal ions. Complex formation needed 5 min in
      microwave oven or 12 min in thermo-block at 95 degrees C. RP-HPLC isocratic
      method (Kinetex 150/4.6 mm; 25% AcN/0.1% TFA, 1 mL/min) with UV/Vis and
      radiometric detection was developed for investigation of the radiolabelled and
      "cold" complexes. For LC-MS investigations, HPLC method was modified replacing
      TFA by formic acid. RESULTS AND DISCUSSION: Yields of CP04 radiolabelling were
      greater than 90% for all three radionuclides. The HPLC method enabled
      identification of these radio-complexes based on comparison to their non
      radioactive equivalents. In all cases, chromatograms revealed peaks that could be
      attributed to the metal-CP04 complexes and to impurities (including methionine
      oxidation). LC-MS analysis of Ga and Lu complexes revealed conformity of the
      observed molecular ions to the predicted formulas (m/z 2116 and 2220 Da for Ga
      and Lu, respectively). Different chromatographic behaviour observed for Ga-CP04
      complex comparing to Lu- and Y- labelled peptide (relative retention to CP04:
      1.08, 0.86 and 0.85, respectively) suggest different coordination of the metal
      ions. Therefore, further studies are planned using the non-radioactive complexes
      in order to assess their structural conformations.

PMID- 26315863
TI  - The nonspecific lymph node uptake of 18F-choline in patients with prostate cancer
      -a prospective observational study.
AB  - BACKGROUND: The aim of this study was to observe and characterize the nonspecific
      18F-choline lymph node uptake in patients with prostate cancer. MATERIAL AND
      METHODS: In this single center, prospective observational study which was done in
      University Hospital Center Zagreb between December 2012 and October 2014, 69
      patients (median age 71 years; range 50-92) with prostate cancer were included.
      Patients underwent 18F-choline PET/CT for staging or restaging of prostate
      cancer. The mean follow-up period was 11.5 months. Kruskal-Wallis test was used
      to find out if the differences between SUV values of specific and nonspecific
      accumulation of the tracer are statistically significant. RESULTS: Nonspecific
      accumulation of 18F-choline in lymph nodes was found in 36 patients (52.7%). Most
      of these findings (n = 24) were nonspecific accumulation of the tracer in
      mediastinal lymph nodes. Other sites of nonspecific tracer uptake were pulmonary
      hila (n = 20), inguinal lymph nodes (n = 15), and axillary lymph nodes (n = 10).
      Mean SUV values for mediastinal lymph nodes, pulmonary hila, axillary and
      inguinal lymph nodes were 4.8, 4.3, 3.1 and 4.1, respectively. Mean SUV value of
      nonspecific sites of tracer accumulation was lower (not significantly; (p = 0.2)
      than tracer uptake values measured in metastases sites (bone metastases mean
      SUVmax value - 13.2, metastatic lymph nodes mean SUVmax value - 9.2).
      CONCLUSIONS: 18F-choline PET/CT is a valuable and an established functional
      diagnostic imaging method for staging and restaging prostate cancer. However,
      nonspecific uptake of the tracer can often be seen in lymph nodes not related to
      primary disease. Patient history, clinical examination, laboratory tests and
      correlation with other imaging methods, must be taken into consideration when
      interpreting 18F-choline PET/CT findings.

PMID- 26315864
TI  - Influence of low grade exercise on skeletal scintigraphy using Tc-99m methylene
      diphosphonate.
AB  - BACKGROUND: Tc-99m methylene diphosphonate [MDP] bone scan is the basis of the
      skeletal imaging in nuclear medicine being a highly sensitive tool for detecting
      bone diseases. Mechanical stimulation induced by low grade exercise or whole-body
      vibration appears to be advantageous regarding the maintenance and/or improvement
      of skeletal mass in humans. We aimed to assess the physiological influence of low
      grade exercise on the quality of skeletal scintigraphy using Tc-99m MDP. MATERIAL
      AND METHODS: Tc-99m MDP bone scan was done for 92 volunteers [Group 1; G1]. Five
      days later, the same subjects were re-scanned [Group 2; G2] after an exercise on
      treadmill for 5 minutes. Image quality was assessed using quantitative measures
      whereby equal regions of interest (ROI) were drawn over the femoral diaphysis,
      and the contralateral adductor area. The total number of counts from the bone [B]
      ROI and soft tissue [ST] ROI was expressed as a ratio [B:ST ratio] and a mean
      value for each was established. RESULTS: Statistically significant difference was
      found between the B:ST ratio means [p = 0.001] in G1 and G2. CONCLUSION: This
      study raised a physiological influence of low grade exercise on the image quality
      of tc-99m MDP skeletal scintigraphy by increasing MDP osseous uptake.

PMID- 26315865
TI  - Studies on the separation of 99mTc from large excess of molybdenum.
AB  - BACKGROUND: Due to aging and unexpected prolonged shutdown of nuclear reactors
      producing 99Mo for 99Mo/ 99mTc generators it was necessary to explore the
      alternative methods of technetium-99m production. The first choice were the
      accelerators. Three years ago IAEA (International Atomic Energy Agency) initiated
      the Coordinated Research Project "Accelerator-based Alternatives to Non-HEU
      production of Mo-99 /Tc-99m" aimed at direct production of 99mTc in proton
      accelerators using the 100Mo(p,2n)99mTc reaction. POLATOM is participating in
      this enterprise together with the Heavy Ion Laboratory of Warsaw University and
      the Institute of Nuclear Chemistry and Technology. MATERIAL AND METHODS:
      99Mo/99mTc solutions and pure 99mTc used for generators production or milked from
      ready to use generators were used in experiments. Commercial chromatographic and
      laboratory-prepared columns were used for separation. The peristaltic pumps were
      used for solutions delivery onto the columns. Radioactivity of eluted 99Mo and
      99mTc was measured using high resolution gamma spectrometry or ionisation chamber
      in case of high radioactivity. For separation, three different chromatographic
      methods were used, one based on ion exchange and two on extraction. RESULTS:
      Synthetic mixtures simulating the real solutions were used. 99mTc is
      quantitatively bound in the Dowex-1 * 8 column whereas molybdenum is only
      slightly retained and totally rinsed with 2M NaOH. 99mTc is eluted with TBAB. The
      elution yield has been reproducible and amounted to 78%. The AnaLig Tc-02 resin
      column was used for 99mTc retention. Residual Mo was removed by rinsing with 2M
      NaOH and 99mTc eluted using small volume of water. The recovery was equal to
      about 85%. Using C-18 column coated with PEG over 80% of 99mTc was recovered in
      about 50 mL of water. The reduction of volume was necessary. CONCLUSIONS: The
      recovery of 99mTc was the highest using AnaLig Tc-02 resin. Time of 99mTc
      separation is the shortest for AnaLig Tc-02 resin and it is not higher than 100
      minutes and it can further be shortened.

PMID- 26315866
TI  - Perfusion lung scintigraphy for the prediction of postoperative residual
      pulmonary function in patients with lung cancer.
AB  - BACKGROUND: Accurate prediction of postoperative pulmonary function in patients
      with non-small cell lung cancer is crucial for proper qualification for surgery,
      the only effective therapeutic method. The aim of the study was to select the
      most accurate method for acquisition and processing of lung perfusion
      scintigraphy (LPS) combined with spirometry for prediction of postoperative
      pulmonary function in patients qualified for surgery. MATERIAL AND METHODS: LPS
      was performed in 70 patients (40 males, 30 females), with preoperative spirometry
      (mean FEV1preop = 2.26 +/- 0.72 L), after administration of 185 MBq of 99mTc
      microalbumin/macroaggregate, using planar (appa) and SPECT/CT methods. Predicted
      postoperative lung function (FEV1pred) was calculated as a part of active lung
      parenchyma to remain after surgery. A non-imaging segment counting method was
      also applied. FEV1pred(appa, SPECT, SPECT/CT, segm.) were further compared with
      actual FEV1postop values obtained from postoperative spirometry. RESULTS: In the
      whole studied group (47 lobectomies, 23 pneumonectomies) mean value of FEV1postop
      was equal to 1.76 (+/- 0.56) L. FEV1pred(appa, SPECT, SPECT/CT, segm.) were equal
      to 1.75 (+/- 0.58) L, 1.71 (+/- 0.57) L, 1.72 (+/- 0.57) L and 1.57 (+/- 0.58) L,
      respectively. A segment counting method systematically lowered predicted FEV1
      values (p < 10-5). Moreover, in 31 patients with FEV1preop < 2 L error of
      predicted values was assessed with Bland-Altman method. Mean absolute differences
      FEV1postop - FEV1pred amounted to: appa - (0.04 +/- 0.13) L, SPECT - (0.07 +/-
      0.14) L, SPECT/CT - (0.06 +/- 0.14) L and segm. - (0.21 +/- 0.19) L,
      respectively. Lower limit of 95% confidence interval calculated for planar -
      optimal method, was equal to -220 mL (also determined separately in subgroups
      after lobectomy and pneumonectomy). CONCLUSIONS: This study shows that planar LPS
      may be applied for prediction of postoperative pulmonary function in patients
      qualified for pneumonectomy and lobectomy. If actual FEV1postop value is to be >=
      800 mL, predicted value should exceed 1000 mL.

PMID- 26315867
TI  - Effect of CT misalignment on attenuation--corrected myocardial perfusion SPECT.
AB  - BACKGROUND: Use of CT based attenuation correction (AC) for myocardial perfusion
      SPECT (MPS) is growing fast due to a rapid development of hybrid SPECT/CT
      systems. SPECT and CT studies are performed in a sequential way extending total
      study acquisition and making a patient movement more likely. The present work
      aims at answering the question how large misalignment between SPECT and CT
      studies should be considered significant and how often those misregistrations are
      observed. MATERIAL AND METHODS: A retrospective study applying AC was performed
      in 107 patients who had coronary angiography (CA) performed within 3 months.
      Patients underwent a stress/rest Tc-99m MIBI 2 day SPECT/CT myocardial perfusion
      study. In case of SPECT and CT misalignment CT slices were shifted manually;
      shifts along 3 axes were recorded and after realignment a repeat reconstruction
      was performed. Euclidean distance of misalignment was also calculated. Images
      were analyzed by two experienced nuclear medicine specialists (consensus)
      applying visual semiquantitative method. Perfusion of three arteries was scored
      using a 5 grade scale. CA results were used as a reference for MPS findings.
      RESULTS: In 47 patients (44%) CT realignment was necessary. CT was shifted mostly
      along x and y axes, and less often along z axis. Euclidean distance S exceeded 2
      pixels in 3 stress and 2 rest studies. Only in 7 patients changes of scores
      assigned to coronary vessels were noted as a result of CT realignment. These
      changes concerned 9 vessel areas. In 7 out of 9 cases changes were noted toward a
      better agreement with results of CA. Only in one patient, with stress S > 3
      pixels and negative result of CA, CT realignment changed vessel area score
      significantly, from probably abnormal to normal. CONCLUSIONS: Only misalignments
      large enough, exceeding 2-3 pixels, have negative impact on attenuation corrected
      images. Such misalignments are rare, in our material were observed in 3 stress
      and 2 rest studies (3% and 2% of all studies, respectively). Only in one patient
      (below 1% of all studied patients) CT misalignment caused a significant study
      misinterpretation. Although alignment of SPECT and CT studies should be checked
      in every patient, small misalignments do not affect study interpretation

PMID- 26315868
TI  - Early brain perfusion improvement after ventriculoperitoneal shunt surgery in
      patients with idiopathic normal pressure hydrocephalus evaluated by 99mTc-HMPAO
      SPECT - preliminary report.
AB  - BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a clinical
      syndrome that consists of the triad: gait disturbance, mental deterioration and
      urinary incontinence associated with normal cerebrospinal fluid pressure (CSF),
      without pre-existing abnormalities. The most popular treatment option is surgical
      implantation of a shunt. Brain perfusion increase occurring months or years after
      successful shunt surgery is well described in the literature. Early improvement
      of perfusion is not well documented. Therefore, the objective of the present
      study was to determine patterns of brain perfusion changes 3-6 days after the
      ventriculoperitoneal shunting in patients with iNPH by using 99mTc-HMPAO SPECT.
      MATERIAL AND METHODS: Sixteen patients with iNPH (9 women, 7 men, mean age 64.1
      +/- 12.7 years) who underwent ventriculoperitoneal shunt surgery were included
      into the study group. Indications for implanting a shunt were based on clinical
      history, neuroimaging and CSF dynamic studies with an infusion test. Brain
      perfusion SPECT was performed 1-2 days before and 3-6 days after the surgical
      treatment. For comparison of perfusion before and after the surgery SPECT scans
      were assessed visually and semiquantitatively with voxel based analysis. RESULTS:
      No side effects were observed after the surgery. Brain perfusion improvement
      after shunting was observed in 10 patients (62.5%). Patterns of perfusion changes
      varied between patients, with combinations of different bilateral and lateralized
      brain regions involved. Perfusion increased in the whole brain (3 patients), in
      the right cerebral hemisphere (1 patient) or in the separate cerebral regions (6
      patients): frontal, parietal, temporal, cerebellum, cingulate gyrus. Perfusion
      improvement was predominantly observed in the frontal lobes: right frontal (3
      cases, 18.8%), left frontal (3 cases, 18.8%). CONCLUSIONS: Cerebral perfusion is
      recovered promptly after ventriculoperitoneal shunt surgery in about 60% of
      patients with iNPH. This improvement may be global or regional in different
      cerebral areas with prevalence of the frontal lobes.

PMID- 26315869
TI  - Long bone metastases as predictors of survival in patients with metastatic renal
      cancer.
AB  - BACKGROUND: The aim of this study was to assess the prevalence of long bone
      metastases in renal cancer patients and to evaluate their utility as predictors
      of survival in this group. MATERIAL AND METHODS: This retrospective study
      included 20 patients with metastatic renal cancer and bone metastases. The
      patients were referred for regular bone scintigraphy in order to assess disease
      spread in the skeleton. The patients were divided into two groups: those with 1)
      metastases in the skeleton (including long bones) and those with 2) metastases in
      the axial skeleton only. RESULTS: Bone scintigraphy imaging was performed
      regularly up to 81 months from the first positive bone scan. During that time 11
      deaths (8 among patients with long bone lesions) were recorded. Kaplan-Meyer
      curves showed that patients with long bone metastases tend to have lower survival
      probability in comparison to the ones with metastases in other bones.
      CONCLUSIONS: Bone metastases localization seems to influence survival in patients
      with renal cancer. Long bone-involving spread of the disease is associated with
      worse survival probability than the spread to the other bones.

PMID- 26315870
TI  - The use of 90Y-PET imaging in evaluation of 90Y-microspheres distribution in the
      liver: initial results.

PMID- 26315871
TI  - 99mTc(V)-DMSA SPECT-CT findings in a case of Gorham-Stout disease.
AB  - The Gorham-Stout disease is a very rare condition, characterized by
      lymphovascular proliferation and massive bone resorption. We present a 48-year
      old male patient with osteolysis involving the left femoral head and neck, as
      well as to the ipsilateral acetabulum. Besides the morphological imaging, he
      underwent bone scintigraphy, technetium-99m-V-dimercaptosuccinic acid [99mTc(V)
      DMSA] single photon emission computed tomography/computed tomography (SPECT/CT)
      and histological examination. Together these findings gave the definitive
      diagnosis. This is the first case ever published with 99mTc(V)-DMSA SPECT-CT.
      Advances on the knowledge of disease suggests that this imaging procedure could
      have utility in diagnosis and evaluation of the disease activity and therapy
      response. 

PMID- 26315872
TI  - 124I-MIBG: a new promising positron-emitting radiopharmaceutical for the
      evaluation of neuroblastoma.
AB  - Neuroblastoma is the most common extra-cranial solid tumor in pediatric patients.
      Despite the established role of 123I-MIBG and 131I-MIBG scintigraphy in this
      tumor, only limited data are available regarding the use of 124I
      metaiodobenzylguanidine (MIBG) positron emission tomography (PET)/computed
      tomography (CT). We present our preliminary experience with 124I-MIBG PET/CT: two
      pediatric patients affected by neuroblastoma, who underwent 124I-MIBG PET/CT for
      pre-therapy distribution evaluation and restaging purposes. We aimed to evaluate
      whether 124I-MIBG PET/CT can detect as many or more neuroblastoma lesions than
      123I/131I-MIBG imaging. Our cases show promising results, although further
      validation and standardization of 124I-MIBG PET/CT are required. 

PMID- 26315873
TI  - Unsual bone metastasis to the rib and the tibia of a follicular variant of
      papillary thyroid carcinoma.
AB  - Usually differentiated thyroid cancer is a slow growing tumor with low metastatic
      potential. We present the case of female patient of 26-years-old who underwent
      thyroidectomy, followed by 3.7 GBq of 131 I. The post-therapeutic whole-body scan
      showed intense uptake in the left part of posterior thorax and a faint
      radioactivity in the upper right tibia. A Chest CT-scan and a localized knee MRI
      confirm that they are bone metastasis in the middle portion of the 8th right rib
      and in the upper tibial metaphysic. 

PMID- 26315874
TI  - Diagnosis and treatment of Graves' disease with particular emphasis on
      appropriate techniques in nuclear medicine. General state of knowledge.
AB  - Graves' disease is an autoimmune disease. It accounts for 50-80% of cases of
      hyperthyroidism. Antibodies against the TSH receptor (TRAb) are responsible for
      hyperthyroidism (TRAB). The key role in monitoring and diagnosis of Graves'
      disease plays the level of hormones of free thyroxine and triiodothyronine.
      Helpful is an ultrasound of the thyroid scintigraphy which due to its functional
      character is both a valuable addition to morphological studies as well as plays
      an important role in the diagnosis and therapy in patients with Graves' disease.
      There is no perfect treatment for Graves' disease. The reason for this is the
      lack of therapy directed against primary pathogenic mechanisms. Currently
      available treatments need to be thoroughly discussed during the first visit as
      the patient's understanding of the choice of a treatment constitutes a vital role
      in the success of therapy. Graves' disease treatment is based on three types of
      therapies that have been carried out for decades including: pharmacological
      treatment anti-thyroid drugs, I131 therapy and radical treatment - thyroidectomy.
      The purpose of the treatment is to control symptoms and patient to return to
      euthyreosis. Treatment of Graves' disease is of great importance because if left
      untreated, it can lead to long-term harmful effects on the heart, bone and mental
      well-being of patients. 

PMID- 26315876
TI  - The effect of magnesium sulphate on intubating condition for rapid-sequence
      intubation: a randomized controlled trial.
AB  - STUDY OBJECTIVES: We compared magnesium sulphate with control, ketamine,
      rocuronium prime, and large-dose rocuronium (0.9 mg/kg) with regard to intubation
      conditions during rapid-sequence induction. DESIGN: This is a prospective,
      randomized, double-blinded study. SETTING: The setting is at an operating room in
      a university-affiliated hospital. PATIENTS: One hundred ten patients scheduled
      for general anesthesia were randomly allocated to the following 5 groups in equal
      numbers. INTERVENTIONS: The control and rocuronium 0.9 groups received rocuronium
      0.6 and 0.9 mg/kg, respectively; the ketamine group was given 0.5 mg/kg ketamine
      2 minutes before 0.6 mg/kg rocuronium; the rocuronium prime group received 0.06
      mg/kg rocuronium 3 minutes before 0.54 mg/kg rocuronium; and the magnesium group
      received 50 mg/kg magnesium sulphate. Intubation was initiated 50 seconds after
      the rocuronium injection. MEASUREMENTS: Intubating condition (primary outcome),
      rocuronium onset, rocuronium duration, train-of-four ratio upon intubation, and
      hemodynamic variables (secondary outcomes) were recorded. MAIN RESULTS: The
      excellent intubating condition was more frequent in the magnesium group (P <
      .05). Onset of neuromuscular block was shorter in the magnesium group than in the
      control, ketamine, and rocuronium prime groups (P < .05). No difference in onset
      time was found between the magnesium and rocuronium 0.9 groups. Block duration
      was longest in the rocuronium 0.9 group. The train-of-four ratio on intubation
      was lowest in the rocuronium prime group. The only adverse event was a burning or
      heat sensation reported by 5 patients in the magnesium group. CONCLUSIONS:
      Magnesium sulphate pretreatment was most likely to provide excellent intubating
      condition for rapid-sequence intubation compared with the control, ketamine
      pretreatment, rocuronium prime, and large-dose rocuronium. However, magnesium
      sulphate administration is associated with a burning or heat sensation.

PMID- 26315877
TI  - Computer simulations of the mechanical response of brushes on the surface of
      cancerous epithelial cells.
AB  - We report a model for atomic force microscopy by means of computer simulations of
      molecular brushes on surfaces of biological interest such as normal and cancerous
      cervical epithelial cells. Our model predicts that the force needed to produce a
      given indentation on brushes that can move on the surface of the cell (called
      "liquid" brushes) is the same as that required for brushes whose ends are fixed
      on the cell's surface (called "solid" brushes), as long as the tip of the
      microscope covers the entire area of the brush. Additionally, we find that
      cancerous cells are softer than normal ones, in agreement with various
      experiments. Moreover, soft brushes are found to display larger resistance to
      compression than stiff ones. This phenomenon is the consequence of the larger
      equilibrium length of the soft brushes and the cooperative association of solvent
      molecules trapped within the brushes, which leads to an increase in the osmotic
      pressure. Our results show that a careful characterization of the brushes on
      epithelial cells is indispensable when determining the mechanical response of
      cancerous cells. 

PMID- 26315878
TI  - Structural Violence in Health Care: Lived Experience of Street-Based Female
      Commercial Sex Workers in Kathmandu.
AB  - Thirty-five in-depth, semi-structured interviews were conducted with female,
      street-based, commercial sex workers in Kathmandu, Nepal. The framework of
      structural violence guided this study in identifying the structural context that
      impacts the female sex workers' lives and may cause harm to their health.
      Structural violence in health care was revealed through thematic analysis as (a)
      discrimination, (b) forced choice, and (c) limitations to health information
      sources. Lived experiences highlight how the sex workers engaged with structural
      limitations in health care access, services, and utilization. Structural violence
      conveys a message about who is entitled to health care and what a society
      emphasizes and expects regarding acceptable health behavior. Examining the
      structural violence highlighted how the sex workers negotiated, understood, and
      engaged with structural limitations in health care access, services, and
      utilization.

PMID- 26315879
TI  - Long-term outcome of endoscopic and surgical resection for foregut neuroendocrine
      tumors.
AB  - OBJECTIVE: Endoscopic resection (ER) of foregut neuroendocrine tumors (NETs) is
      increasingly performed instead of surgery. This study aimed to compare the long
      term therapeutic outcomes of ER and surgical resection (SR) for foregut NETs.
      METHODS: From 2002 to 2012, a total of 49 patients with histologically confirmed
      foregut NETs were treated by ER (n = 33) and SR (n = 16). The clinicopathological
      characteristics and therapeutic outcomes were evaluated. RESULTS: Of the 33
      patients who underwent ER [endoscopic mucosal resection (n = 26), endoscopic
      mucosal dissection (n = 7)], 32 were diagnosed as NET-G1 and NET-G2, and the
      other as neuroendocrine carcinoma (NEC). Of the 16 patients who underwent SR, 10
      were diagnosed as NET-G1, 2 as NET-G2 and 4 as NEC. The median tumor size was
      significantly smaller in the ER group compared with the SR group (7 mm vs 19 mm,
      P = 0.001). In almost all patients treated with ER (32/33), NET invasion was
      limited to the mucosa and submucosa. Non-curative resections were observed in
      24.2% of the patients in the ER group (8/33) and 25.0% in the SR group (4/16). No
      recurrence occurred in NET cases with positive resection margins by ER. However,
      all cases of non-curative resection with lymphatic invasion (one in the ER group
      and four in the SR group) developed liver metastasis during the follow-up despite
      complete resection, and all these five patients has histologically confirmed
      NECs. CONCLUSION: NET patients treated by ER may have a good prognosis if the
      tumor size is small and histologically low grade without lymphatic invasion.

PMID- 26315880
TI  - Newborn Screening for Lysosomal Storage Disorders: Views of Genetic Healthcare
      Providers.
AB  - Lysosomal storage diseases (LSDs), lysosomal enzyme deficiencies causing multi
      system organ damage, have come to the forefront in newborn screening (NBS)
      initiatives due to new screening technologies and emerging treatments. We
      developed a qualitative discussion tool to explore opinions of genetic healthcare
      providers (HCPs) regarding population-based NBS for MPS types 1 and 2, Pompe,
      Gaucher, Fabry, and Krabbe diseases. Thirty-eight telephone interviews conducted
      by a single researcher were analyzed and coded for thematic trends. Six major
      themes emerged: 1) treatment availability and efficacy is crucial; 2) early age
      of disease onset is important; 3) ambiguity regarding prognosis is undesirable;
      4) parents' ability to make reproductive decisions is seen by some as a benefit
      of NBS; 5) paucity of resources for follow-up exists; and 6) the decision-making
      process for adding conditions to mandated NBS is concerning to HCPs. Among the
      LSDs discussed, Pompe was considered most appropriate, and Krabbe least
      appropriate, for NBS. MPS1 and MPS2 were overall considered favorably for
      screening, but MPS1 ranked higher, due to a perception of better efficacy of
      therapeutic options. Fabry and Gaucher diseases were viewed less favorably due to
      later age of onset. The themes identified in this study must be addressed by
      decision-makers in expanding NBS for LSDs and may be applied to many diseases
      being considered for NBS in the future.

PMID- 26315881
TI  - Human amniotic mesenchymal stromal cells (hAMSCs) as potential vehicles for drug
      delivery in cancer therapy: an in vitro study.
AB  - INTRODUCTION: In the context of drug delivery, mesenchymal stromal cells (MSCs)
      from bone marrow and adipose tissue have emerged as interesting candidates due to
      their homing abilities and capacity to carry toxic loads, while at the same time
      being highly resistant to the toxic effects. Amongst the many sources of MSCs
      which have been identified, the human term placenta has attracted particular
      interest due to its unique, tissue-related characteristics, including its high
      cell yield and virtually absent expression of human leukocyte antigens and co
      stimulatory molecules. Under basal, non-stimulatory conditions, placental MSCs
      also possess basic characteristics common to MSCs from other sources. These
      include the ability to secrete factors which promote cell growth and tissue
      repair, as well as immunomodulatory properties. The aim of this study was to
      investigate MSCs isolated from the amniotic membrane of human term placenta
      (hAMSCs) as candidates for drug delivery in vitro. METHODS: We primed hAMSCs from
      seven different donors with paclitaxel (PTX) and investigated their ability to
      resist the cytotoxic effects of PTX, to upload the drug, and to release it over
      time. We then analyzed whether the uptake and release of PTX was sufficient to
      inhibit proliferation of CFPAC-1, a pancreatic tumor cell line sensitive to PTX.
      RESULTS: For the first time, our study shows that hAMSCs are highly resistant to
      PTX and are not only able to uptake the drug, but also release it over time.
      Moreover, we show that PTX is released from hAMSCs in a sufficient amount to
      inhibit tumor cell proliferation, whilst some of the PTX is also retained within
      the cells. CONCLUSION: Taken together, for the first time our results show that
      placental stem cells can be used as vehicles for the delivery of cytotoxic
      agents.

PMID- 26315882
TI  - Dendritic Remodeling: Lessons from Invertebrate Model Systems.
AB  - Dendrites are the entry site of neural signals into neurons. Once formed,
      dendrites are not just the same in structure but rather are dynamically remodeled
      in vivo: some dendrites are pruned away, while others lengthen and branch out.
      Dendritic remodeling occurs not only during neural development, but also in
      mature dendrites under both physiological and pathological conditions, suggesting
      its contribution to neural plasticity. The underlying cellular and molecular
      mechanisms remained poorly understood until recently, but they are just beginning
      to be elucidated from recent studies on invertebrate model systems. Here, we
      review recent advances in our understanding of how dendrites are remodeled by
      focusing particularly on insights obtained from Drosophila sensory neurons. 

PMID- 26315883
TI  - Connexins: Intercellular Signal Transmitters in Lymphohematopoietic Tissues.
AB  - Life-long hematopoietic demands are met by a pool of hematopoietic stem cells
      (HSC) with self-renewal and multipotential differentiation ability. Humoral and
      paracrine signals from the bone marrow (BM) hematopoietic microenvironment
      control HSC activity. Cell-to-cell communication through connexin (Cx) containing
      gap junctions (GJs) allows pluricellular coordination and synchronization through
      transfer of small molecules with messenger activity. Hematopoietic and
      surrounding nonhematopoietic cells communicate each other through GJs, which
      regulate fetal and postnatal HSC content and function in hematopoietic tissues.
      Traffic of HSC between peripheral blood and BM is also dependent on Cx proteins.
      Cx mutations are associated with human disease and hematopoietic dysfunction and
      Cx signaling may represent a target for therapeutic intervention. In this review,
      we illustrate and highlight the importance of Cxs in the regulation of
      hematopoietic homeostasis under normal and pathological conditions. 

PMID- 26315884
TI  - Engineered Minichromosomes in Plants: Structure, Function, and Applications.
AB  - Engineered minichromosomes are small chromosomes that contain a transgene and
      selectable marker, as well as all of the necessary components required for
      maintenance in an organism separately from the standard chromosome set. The
      separation from endogenous chromosomes makes engineered minichromosomes useful in
      the production of transgenic plants. Introducing transgenes to minichromosomes
      does not have the risk of insertion within a native gene; additionally,
      transgenes on minichromosomes can be transferred between lines without the
      movement of linked genes. Of the two methods proposed for creating engineered
      minichromosomes, telomere-mediated truncation is more reliable in plant systems.
      Additionally, many plants contain a supernumerary, or B chromosome, which is an
      excellent starting material for minichromosome creation. The use of site-specific
      recombination systems in minichromosomes can increase their utility, allowing for
      the addition or subtraction of transgenes in vivo. The creation of
      minichromosomes with binary bacterial artificial chromosome vectors provides the
      ability to introduce many transgenes at one time. Furthermore, coupling
      minichromosomes with haploid induction systems can facilitate transfer between
      lines. Minichromosomes can be introduced to a haploid-inducing line and crossed
      to target lines. Haploids of the target line that then contain a minichromosome
      can then be doubled. These homozygous lines will contain the transgene without
      the need for repeated introgressions. 

PMID- 26315885
TI  - New Insights into the Role of Ubiquitin Networks in the Regulation of
      Antiapoptosis Pathways.
AB  - Ubiquitin is a small modifier protein that conjugates on lysine (Lys) residues of
      substrates, and it can be targeted by another ubiquitin molecule to form chains
      through conjugation on the intrinsic Lys residues and methionine (Met) 1 residue.
      Ubiquitination of substrates by such chains determines the fate of substrates,
      thereby influencing various biological processes. In this chapter, we focus on
      apoptosis with an emphasis on the regulation by ubiquitination. The signal
      transduction of apoptosis is governed not only by the classical function of
      ubiquitin, which is proteasome-dependent degradation of substrates, but also by
      the apoptosis signaling complex formation guided by different types of ubiquitin
      chains. Ubiquitinations of pro- and antiapoptotic proteins are tightly regulated
      by particular sets of enzymes, such as ubiquitin E3 ligases and deubiquitinases
      (DUBs). We further discuss ubiquitination in the tumor necrosis factor (TNF)
      signaling pathway as an example for the ubiquitin-dependent regulation of
      apoptosis and cell survival. 

PMID- 26315886
TI  - Formation of Tubulovesicular Carriers from Endosomes and Their Fusion to the
      trans-Golgi Network.
AB  - Endosomes undergo extensive spatiotemporal rearrangements as proteins and lipids
      flux through them in a series of fusion and fission events. These controlled
      changes enable the concentration of cargo for eventual degradation while ensuring
      the proper recycling of other components. A growing body of studies has now
      defined multiple recycling pathways from endosomes to the trans-Golgi network
      (TGN) which differ in their molecular machineries. The recycling process requires
      specific sets of lipids, coats, adaptors, and accessory proteins that coordinate
      cargo selection with membrane deformation and its association with the
      cytoskeleton. Specific tethering factors and SNARE (SNAP (Soluble NSF Attachment
      Protein) Receptor) complexes are then required for the docking and fusion with
      the acceptor membrane. Herein, we summarize some of the current knowledge of the
      machineries that govern the retrograde transport from endosomes to the TGN. 

PMID- 26315887
TI  - Insights into Transcriptional Regulation of Hepatic Glucose Production.
AB  - Maintenance of systemic glucose homeostasis is pivotal in animals because most
      tissues, especially brain and red blood cells, rely on glucose as the sole energy
      source. The liver protects the body from hypoglycemia because it possesses two
      biochemical pathways, namely gluconeogenesis and glycogenolysis which provide
      glucose during starvation period. Posttranslational regulation by allosteric
      effectors and/or reversible phosphorylation of the key enzymes involved in these
      two pathways provide the rapid response for the immediate increase in the enzyme
      activities to accelerate rates of gluconeogenesis and glycogenolysis, but these
      mechanisms are insufficient for long-term control. Glucoregulatory hormones can
      alter the rate of enzyme synthesis at the transcriptional step by modulating the
      key transcription factors and coactivators, such as CREB/CRTC2, FoxO1, nuclear
      receptors, C/EBPalpha, hepatocyte nuclear factors, PGC1alpha, and CLOCK genes.
      Precise and well-coordinated regulation of activities of these transcription
      factors at the right time enables liver to synthesize or suppress glucose
      production, thus maintaining the proper function of tissues and organs during
      starvation and feeding cycles. Loss of function mutation or deregulation of these
      key transcription factors and coactivators can result in the pathophysiological
      condition, such as type 2 diabetes. 

PMID- 26315888
TI  - Tropomyosin as a Regulator of Actin Dynamics.
AB  - Tropomyosin is a major regulatory protein of contractile systems and
      cytoskeleton, an actin-binding protein that positions laterally along actin
      filaments and modulates actin-myosin interaction. About 40 tropomyosin isoforms
      have been found in a variety of cytoskeleton systems, not necessarily connected
      with actin-myosin interaction and contraction. Involvement of specific
      tropomyosin isoforms in the regulation of key cell processes was shown, and
      specific features of tropomyosin genes and protein structure have been
      investigated with molecular biology and genetics approaches. However, the
      mechanisms underlying the effects of tropomyosin on cytoskeleton dynamics are
      still unclear. As tropomyosin is primarily an F-actin-binding protein, it is
      important to understand how it interacts both with actin and actin-binding
      proteins functioning in muscles and cytoskeleton to regulate actin dynamics. This
      review focuses on biochemical data on the effects of tropomyosin on actin
      assembly and dynamics, as well as on the modulation of these effects by actin
      binding proteins. The data indicate that tropomyosin can efficiently regulate
      actin dynamics via allosteric conformational changes within actin filaments. 

PMID- 26315889
TI  - Battery-powered bone drill: caution needed in densely blastic lesions.
AB  - Image-guided biopsies play an important role for pathologic diagnosis of bone
      tumors. Recently, motorized, battery powered bone marrow biopsy devices have been
      used to biopsy focal bone lesions with high accuracy. We present here two cases
      of densely blastic metastases where the biopsy sample could not be removed from
      the needle. These two cases suggest that if the lesion is densely blastic, then
      the sample should be small (<5 mm) to ensure that the biopsy specimen will not be
      stuck within the biopsy needle. 

PMID- 26315891
TI  - Enhancing Tabletop X-Ray Phase Contrast Imaging with Nano-Fabrication.
AB  - X-ray phase-contrast imaging is a promising approach for improving soft-tissue
      contrast and lowering radiation dose in biomedical applications. While current
      tabletop imaging systems adapt to common x-ray tubes and large-area detectors by
      employing absorptive elements such as absorption gratings or monolithic crystals
      to filter the beam, we developed nanometric phase gratings which enable tabletop
      x-ray far-field interferometry with only phase-shifting elements, leading to a
      substantial enhancement in the performance of phase contrast imaging. In a
      general sense the method transfers the demands on the spatial coherence of the x
      ray source and the detector resolution to the feature size of x-ray phase masks.
      We demonstrate its capabilities in hard x-ray imaging experiments at a fraction
      of clinical dose levels and present comparisons with the existing Talbot-Lau
      interferometer and with conventional digital radiography. 

PMID- 26315892
TI  - The effect of intense exercise periods on physical and technical performance
      during elite Australian Football match-play: A comparison of experienced and less
      experienced players.
AB  - OBJECTIVES: The physical and technical responses of experienced (>=5 years) and
      less experienced (1-4 years) elite Australian Football (AF) players were compared
      following the most intense passages of match-play. DESIGN: Descriptive cohort
      study. METHODS: Time-motion analyses were performed using global positioning
      systems (MinimaxX S4, Catapult Innovations, Melbourne, Australia) on one elite AF
      team during 13 matches. The global positioning data were categorised into total
      distance, low-speed activity (0-2.78ms(-1)), moderate-speed running (2.79-4.14ms(
      1)) and high-speed running (>=4.15ms(-1)) distances. A standardised 5-point
      technical coding criteria was used to rate the number and quality of skill
      involvements during match-play. RESULTS: Following the most intense 3-min running
      period the experienced players covered greater distances at high-speeds in match
      quarters two (effect size, ES=0.42+/-0.30) and three (ES=0.38+/-0.33) than their
      less experienced counterparts. Compared with less experienced players,
      experienced players performed more skill involvements during the second quarter
      (ES=0.42+/-0.33) and fourth quarter peak 3-min bouts of exercise intensity
      (ES=0.40+/-0.30) and quarter one (ES=0.49+/-0.29) and three subsequent periods
      (ES=0.33+/-0.20). CONCLUSIONS: Less experienced players exhibited greater
      reductions in physical and technical performance following peak periods of match
      play. These findings suggest that training may require a greater emphasis on
      developing the ability of less experienced players to maintain physical
      performance and gain possession of the football following intense periods of
      match-play.

PMID- 26315890
TI  - Promotion of Inflammatory Arthritis by Interferon Regulatory Factor 5 in a Mouse
      Model.
AB  - OBJECTIVE: Polymorphisms in the transcription factor interferon regulatory factor
      5 (IRF5) are associated with an increased risk of developing rheumatoid arthritis
      (RA). This study was undertaken to determine the role of IRF5 in a mouse model of
      arthritis development. METHODS: K/BxN serum-transfer arthritis was induced in
      mice deficient in IRF5, or lacking IRF5 only in myeloid cells, and arthritis
      severity was evaluated. K/BxN arthritis was also induced in mice deficient in
      TRIF, Toll-like receptor 2 (TLR2), TLR3, TLR4, and TLR7 to determine the pathways
      through which IRF5 might promote arthritis. In vitro studies were performed to
      determine the role of IRF5 in interleukin-1 (IL-1) receptor and TLR signaling.
      RESULTS: Arthritis severity was reduced in IRF5-deficient, TRIF-deficient, TLR3
      deficient, and TLR7-deficient mice. The expression of multiple genes regulating
      neutrophil recruitment or function and bioactive IL-1beta formation was reduced
      in the joints during active arthritis in IRF5-deficient mice. In vitro studies
      showed that TLR7 and the TRIF-dependent TLR3 pathway induce proinflammatory
      cytokine production in disease-relevant cell types in an IRF5-dependent manner.
      CONCLUSION: Our findings indicate that IRF5 contributes to disease pathogenesis
      in inflammatory arthritis. This is likely due at least in part to the role of
      IRF5 in mediating proinflammatory cytokine production downstream of TLR7 and
      TLR3. Since TLR7 and TLR3 are both RNA-sensing TLRs, this suggests that
      endogenous RNA ligands present in the inflamed joint promote arthritis
      development. These findings may be relevant to human RA, since RNA capable of
      activating TLR7 and TLR3 is present in synovial fluid and TLR7 and TLR3 are up
      regulated in the joints of RA patients.

PMID- 26315893
TI  - Collapse of the echinoid Paracentrotus lividus populations in the Eastern
      Mediterranean--result of climate change?
AB  - The European purple sea urchin (Paracentrotus lividus) is considered to be a key
      herbivore throughout its distribution range--North-East Atlantic and
      Mediterranean Sea. It was also abundant in its eastern distributional edge, on
      rocky habitats of the coastline of Israel, but its populations have recently
      collapsed, and today it is an extremely rare species in the region. Field and
      laboratory experiments, that were carried out in order to examine the impact of
      the recent sea surface temperature rise in the Eastern Mediterranean, showed
      massive urchin mortality when temperatures crossed 30.5  degrees C before
      reaching peak summer values. These results suggest that elevated seawater
      temperatures in recent years may be a main cause for the disappearance of P.
      lividus from the southeast Mediterranean Sea, which may indicate distributional
      range contraction in this region.

PMID- 26315894
TI  - A general framework for comparative Bayesian meta-analysis of diagnostic studies.
AB  - BACKGROUND: Selecting the most effective diagnostic method is essential for
      patient management and public health interventions. This requires evidence of the
      relative performance of alternative tests or diagnostic algorithms. Consequently,
      there is a need for diagnostic test accuracy meta-analyses allowing the
      comparison of the accuracy of two or more competing tests. The meta-analyses are
      however complicated by the paucity of studies that directly compare the
      performance of diagnostic tests. A second complication is that the diagnostic
      accuracy of the tests is usually determined through the comparison of the index
      test results with those of a reference standard. These reference standards are
      presumed to be perfect, i.e. allowing the classification of diseased and non
      diseased subjects without error. In practice, this assumption is however rarely
      valid and most reference standards show false positive or false negative results.
      When an imperfect reference standard is used, the estimated accuracy of the tests
      of interest may be biased, as well as the comparisons between these tests.
      METHODS: We propose a model that allows for the comparison of the accuracy of two
      diagnostic tests using direct (head-to-head) comparisons as well as indirect
      comparisons through a third test. In addition, the model allows and corrects for
      imperfect reference tests. The model is inspired by mixed-treatment comparison
      meta-analyses that have been developed for the meta-analysis of randomized
      controlled trials. As the model is estimated using Bayesian methods, it can
      incorporate prior knowledge on the diagnostic accuracy of the reference tests
      used. RESULTS: We show the bias that can result from using inappropriate methods
      in the meta-analysis of diagnostic tests and how our method provides more correct
      estimates of the difference in diagnostic accuracy between two tests. As an
      illustration, we apply this model to a dataset on visceral leishmaniasis
      diagnostic tests, comparing the accuracy of the RK39 dipstick with that of the
      direct agglutination test. CONCLUSIONS: Our proposed meta-analytic model can
      improve the comparison of the diagnostic accuracy of competing tests in a
      systematic review. This is however only true if the studies and especially
      information on the reference tests used are sufficiently detailed. More
      specifically, the type and exact procedures used as reference tests are needed,
      including any cut-offs used and the number of subjects excluded from full
      reference test assessment. If this information is lacking, it may be better to
      limit the meta-analysis to direct comparisons.

PMID- 26315895
TI  - Comparative Assessment of Oral Mesenchymal Stem Cells Isolated from Healthy and
      Diseased Tissues.
AB  - The aim of the present study was to isolate human mesenchymal stem cells (MSCs)
      from palatal connective and periodontal granulation tissues and to comparatively
      evaluate their properties. MSCs were isolated using the explant culture method.
      Adherence to plastic, specific antigen makeup, multipotent differentiation
      potential, functionality, and ultrastructural characteristics were investigated.
      The frequency of colony-forming unit fibroblasts for palatal-derived mesenchymal
      stem cells (pMSCs) was significantly higher than that of granulation tissue
      derived mesenchymal stem cells (gtMSCs). A significantly higher population
      doubling time and lower migration potential were recorded for gtMSCs than for
      pMSCs. Both cell lines were positive for CD105, CD73, CD90, CD44, and CD49f, and
      negative for CD34, CD45, and HLA-DR, but the level of expression was different.
      MSCs from both sources were relatively uniform in their ultrastructure.
      Generally, both cell lines possessed a large, irregular-shaped euchromatic
      nucleus, and cytoplasm rich in mitochondria, lysosomes, and endoplasmic
      reticulum. The periphery of the plasma membrane displayed many small filopodia.
      MSCs from both cell lines were successfully differentiated into osteogenic,
      adiopogenic, and chondrogenic lineages. Both healthy and diseased tissues may be
      considered as valuable sources of MSCs for regenerative medicine owing to the
      high acceptance and fewer complications during harvesting. 

PMID- 26315896
TI  - Different extenders in the cryopreservation of bovine epididymal spermatozoa.
AB  - The objective of this study was to evaluate the effects of two different egg yolk
      extenders incubated with or without Sperm Talp on the motility and plasma
      membrane integrity of cryopreserved bovine epididymal spermatozoa after freezing.
      Twenty-five testicles with epididymides from mature bulls were collected at the
      abattoir. Epididymal sperm recovery was performed by retrograde flushing using a
      skim milk-extender (Botu-SemenTM). After recovery, sperm were incubated either
      without or with Sperm Talp and then submitted to centrifugation. For the freezing
      process, half of the testes were processed with Tris egg yolk extender, and half
      were processed with Botu-BovTM egg yolk extender. Samples incubated in Sperm Talp
      exhibited better results than epididymal spermatozoa that were incubated without
      Sperm Talp (p<0.05). Both Botu-BovTM and Tris could be utilised to freeze sperm
      from the bovine epididymides if the sperm were previously incubated with Sperm
      Talp. The extenders examined in this work did not differ in their effect on
      plasma membrane integrity after freezing. 

PMID- 26315897
TI  - Predictors of Outcomes in Diabetic Foot Osteomyelitis Treated Initially With
      Conservative (Nonsurgical) Medical Management: A Retrospective Study.
AB  - The optimal way to manage diabetic foot osteomyelitis remains uncertain, with
      debate in the literature as to whether it should be managed conservatively (ie,
      nonsurgically) or surgically. We aimed to identify clinical variables that
      influence outcomes of nonsurgical management in diabetic foot osteomyelitis. We
      conducted a retrospective study of consecutive patients with diabetes presenting
      to a tertiary center between 2007 and 2011 with foot osteomyelitis initially
      treated with nonsurgical management. Remission was defined as wound healing with
      no clinical or radiological signs of osteomyelitis at the initial or contiguous
      sites 12 months after clinical and/or radiological resolution. Nine demographic
      and clinical variables including osteomyelitis site and presence of foot pulses
      were analyzed. We identified 100 cases, of which 85 fulfilled the criteria for
      analysis. After a 12-month follow-up period, 54 (63.5%) had achieved remission
      with nonsurgical management alone with a median (interquartile range) duration of
      antibiotic treatment of 10.8 (10.1) weeks. Of these, 14 (26%) were admitted for
      intravenous antibiotics. The absence of pedal pulses in the affected foot (n =
      34) was associated with a significantly longer duration of antibiotic therapy to
      achieve remission, 8.7 (7.1) versus 15.9 (13.3) weeks (P = .003). Osteomyelitis
      affecting the metatarsal was more likely to be amputated than other sites of the
      foot (P = .016). In line with previous data, we have shown that almost two thirds
      of patients presenting with osteomyelitis healed without undergoing surgical bone
      resection. 

PMID- 26315899
TI  - 15th International Workshop on Co-morbidities and Adverse Drug Reactions in HIV.

PMID- 26315898
TI  - Opuntia Extract Reduces Scar Formation in Rabbit Ear Model: A Randomized
      Controlled Study.
AB  - The purpose of this article is to investigate the effect of Opuntia stricta H
      (Cactaceae) extract on suppression of hypertrophic scar on ventral surface wounds
      of rabbit ears. Full thickness skin defection was established in a rabbit ear to
      simulate hypertrophic scar. Opuntia extract was sprayed on the wounds in the
      experimental group, and normal saline was used in the control group. After the
      wounds healed with scar formation, the hypertrophic scar tissue was harvested on
      days 22, 39, and 54 for histological analysis. The expression of type I and type
      III collagen and matrix metalloproteinase-1 (MMP-1) were evaluated by
      immunohistochemistry and real-time quantitative polymerase chain reaction. The
      results indicated that the scar of the control group is more prominent compared
      with the opuntia extract group. The expression of type I collagen in the opuntia
      extract group was lower than the control group, while type III collagen in
      opuntia extract group gradually increased and exceeded control group. The
      expression of MMP-1 decreased in the opuntia extract group, while the control
      group increased over time, but the amount of MMP-1 was much higher than that in
      the control group on day 22. In conclusion, opuntia extract reduces hypertrophic
      scar formation by means of type I collagen inhibition, and increasing type III
      collagen and MMP-1.T he novel application of opuntia extract may lead to
      innovative and effective antiscarring therapies. 

PMID- 26315900
TI  - InteractiveROSETTA: a graphical user interface for the PyRosetta protein modeling
      suite.
AB  - Modern biotechnical research is becoming increasingly reliant on computational
      structural modeling programs to develop novel solutions to scientific questions.
      Rosetta is one such protein modeling suite that has already demonstrated wide
      applicability to a number of diverse research projects. Unfortunately, Rosetta is
      largely a command-line-driven software package which restricts its use among non
      computational researchers. Some graphical interfaces for Rosetta exist, but
      typically are not as sophisticated as commercial software. Here, we present
      InteractiveROSETTA, a graphical interface for the PyRosetta framework that
      presents easy-to-use controls for several of the most widely used Rosetta
      protocols alongside a sophisticated selection system utilizing PyMOL as a
      visualizer. InteractiveROSETTA is also capable of interacting with remote Rosetta
      servers, facilitating sophisticated protocols that are not accessible in
      PyRosetta or which require greater computational resources. AVAILABILITY AND
      IMPLEMENTATION: InteractiveROSETTA is freely available at
      https://github.com/schenc3/InteractiveROSETTA/releases and relies upon a separate
      download of PyRosetta which is available at http://www.pyrosetta.org after
      obtaining a license (free for academic use).

PMID- 26315901
TI  - LncRNA-ID: Long non-coding RNA IDentification using balanced random forests.
AB  - MOTIVATION: Long non-coding RNAs (lncRNAs), which are non-coding RNAs of length
      above 200 nucleotides, play important biological functions such as gene
      expression regulation. To fully reveal the functions of lncRNAs, a fundamental
      step is to annotate them in various species. However, as lncRNAs tend to encode
      one or multiple open reading frames, it is not trivial to distinguish these long
      non-coding transcripts from protein-coding genes in transcriptomic data. RESULTS:
      In this work, we design a new tool that calculates the coding potential of a
      transcript using a machine learning model (random forest) based on multiple
      features including sequence characteristics of putative open reading frames,
      translation scores based on ribosomal coverage, and conservation against
      characterized protein families. The experimental results show that our tool
      competes favorably with existing coding potential computation tools in lncRNA
      identification. AVAILABILITY AND IMPLEMENTATION: The scripts and data can be
      downloaded at https://github.com/zhangy72/LncRNA-ID.

PMID- 26315902
TI  - database.bio: a web application for interpreting human variations.
AB  - Rapid advances of next-generation sequencing technology have led to the
      integration of genetic information with clinical care. Genetic basis of diseases
      and response to drugs provide new ways of disease diagnosis and safer drug usage.
      This integration reveals the urgent need for effective and accurate tools to
      analyze genetic variants. Due to the number and diversity of sources for
      annotation, automating variant analysis is a challenging task. Here, we present
      database.bio, a web application that combines variant annotation, prioritization
      and visualization so as to support insight into the individual genetic
      characteristics. It enhances annotation speed by preprocessing data on a
      supercomputer, and reduces database space via a unified database representation
      with compressed fields. AVAILABILITY AND IMPLEMENTATION: Freely available at
      https://database.bio.

PMID- 26315903
TI  - Bayexer: an accurate and fast Bayesian demultiplexer for Illumina sequences.
AB  - Demultiplexing is used after high-throughput sequencing to in silico assign reads
      to the samples of origin based on the sequenced reads of the indices. Existing
      demultiplexing tools based on the similarity between the read index and the
      reference index sequences may fail to provide satisfactory results on low-quality
      datasets. We developed Bayexer, a Bayesian demultiplexing algorithm for Illumina
      sequencers. Bayexer uses the information extracted directly from the contaminant
      sequences of the targeting reads as the training dataset for a naive Bayes
      classifier to assign reads. According to our evaluation, Bayexer provides higher
      capability, accuracy and speed on various real datasets than other tools.
      AVAILABILITY AND IMPLEMENTATION: Bayexer is implemented in Perl and freely
      available at https://github.com/HaisiYi/Bayexer.

PMID- 26315904
TI  - LIBRA: LIgand Binding site Recognition Application.
AB  - MOTIVATION: In recent years, structural genomics and ab initio molecular modeling
      activities are leading to the availability of a large number of structural models
      of proteins whose biochemical function is not known. The aim of this study was
      the development of a novel software tool that, given a protein's structural
      model, predicts the presence and identity of active sites and/or ligand binding
      sites. RESULTS: The algorithm implemented by ligand binding site recognition
      application (LIBRA) is based on a graph theory approach to find the largest
      subset of similar residues between an input protein and a collection of known
      functional sites. The algorithm makes use of two predefined databases for active
      sites and ligand binding sites, respectively, derived from the Catalytic Site
      Atlas and the Protein Data Bank. Tests indicate that LIBRA is able to identify
      the correct binding/active site in 90% of the cases analyzed, 90% of which
      feature the identified site as ranking first. As far as ligand binding site
      recognition is concerned, LIBRA outperforms other structure-based ligand binding
      sites detection tools with which it has been compared. AVAILABILITY AND
      IMPLEMENTATION: The application, developed in Java SE 7 with a Swing GUI
      embedding a JMol applet, can be run on any OS equipped with a suitable Java
      Virtual Machine (JVM), and is available at the following URL:
      http://www.computationalbiology.it/software/LIBRAv1.zip.

PMID- 26315905
TI  - EPGA2: memory-efficient de novo assembler.
AB  - MOTIVATION: In genome assembly, as coverage of sequencing and genome size
      growing, most current softwares require a large memory for handling a great deal
      of sequence data. However, most researchers usually cannot meet the requirements
      of computing resources which prevent most current softwares from practical
      applications. RESULTS: In this article, we present an update algorithm called
      EPGA2, which applies some new modules and can bring about improved assembly
      results in small memory. For reducing peak memory in genome assembly, EPGA2
      adopts memory-efficient DSK to count K-mers and revised BCALM to construct De
      Bruijn Graph. Moreover, EPGA2 parallels the step of Contigs Merging and adds
      Errors Correction in its pipeline. Our experiments demonstrate that all these
      changes in EPGA2 are more useful for genome assembly. AVAILABILITY AND
      IMPLEMENTATION: EPGA2 is publicly available for download at
      https://github.com/bioinfomaticsCSU/EPGA2.

PMID- 26315906
TI  - An interactive genome browser of association results from the UK10K cohorts
      project.
AB  - High-throughput sequencing technologies survey genetic variation at genome scale
      and are increasingly used to study the contribution of rare and low-frequency
      genetic variants to human traits. As part of the Cohorts arm of the UK10K
      project, genetic variants called from low-read depth (average 7*) whole genome
      sequencing of 3621 cohort individuals were analysed for statistical associations
      with 64 different phenotypic traits of biomedical importance. Here, we describe a
      novel genome browser based on the Biodalliance platform developed to provide
      interactive access to the association results of the project. AVAILABILITY AND
      IMPLEMENTATION: The browser is available at http://www.uk10k.org/dalliance.html.
      Source code for the Biodalliance platform is available under a BSD license from
      http://github.com/dasmoth/dalliance, and for the LD-display plugin and backend
      from http://github.com/dasmoth/ldserv.

PMID- 26315907
TI  - Fast and accurate approximate inference of transcript expression from RNA-seq
      data.
AB  - MOTIVATION: Assigning RNA-seq reads to their transcript of origin is a
      fundamental task in transcript expression estimation. Where ambiguities in
      assignments exist due to transcripts sharing sequence, e.g. alternative isoforms
      or alleles, the problem can be solved through probabilistic inference. Bayesian
      methods have been shown to provide accurate transcript abundance estimates
      compared with competing methods. However, exact Bayesian inference is intractable
      and approximate methods such as Markov chain Monte Carlo and Variational Bayes
      (VB) are typically used. While providing a high degree of accuracy and modelling
      flexibility, standard implementations can be prohibitively slow for large
      datasets and complex transcriptome annotations. RESULTS: We propose a novel
      approximate inference scheme based on VB and apply it to an existing model of
      transcript expression inference from RNA-seq data. Recent advances in VB
      algorithmics are used to improve the convergence of the algorithm beyond the
      standard Variational Bayes Expectation Maximization algorithm. We apply our
      algorithm to simulated and biological datasets, demonstrating a significant
      increase in speed with only very small loss in accuracy of expression level
      estimation. We carry out a comparative study against seven popular alternative
      methods and demonstrate that our new algorithm provides excellent accuracy and
      inter-replicate consistency while remaining competitive in computation time.
      AVAILABILITY AND IMPLEMENTATION: The methods were implemented in R and C++, and
      are available as part of the BitSeq project at github.com/BitSeq. The method is
      also available through the BitSeq Bioconductor package. The source code to
      reproduce all simulation results can be accessed via
      github.com/BitSeq/BitSeqVB_benchmarking.

PMID- 26315908
TI  - HiXCorr: a portable high-speed XCorr engine for high-resolution tandem mass
      spectrometry.
AB  - Peptide identification is an important problem in proteomics. One of the most
      popular scoring schemes for peptide identification is XCorr (cross-correlation).
      Since calculating XCorr is computationally intensive, a lot of efforts have been
      made to develop fast XCorr engines. However, the existing XCorr engines are not
      suitable for high-resolution MS/MS spectrometry because they are either slow or
      require a specific type of CPU. We present a portable high-speed XCorr engine for
      high-resolution tandem mass spectrometry by developing a novel algorithm for
      calculating XCorr. The algorithm enables XCorr calculation 1.25-49 times faster
      than previous algorithms for 0.01 Da fragment tolerance. Furthermore, our engine
      is easily portable to any machine with different types of CPU because it is
      developed in C language. Hence, our XCorr engine will expedite peptide
      identification by high-resolution tandem mass spectrometry. AVAILABILITY AND
      IMPLEMENTATION: Available at http://isa.hanyang.ac.kr/HiXCorr/HiXCorr.html.

PMID- 26315909
TI  - glmgraph: an R package for variable selection and predictive modeling of
      structured genomic data.
AB  - One central theme of modern high-throughput genomic data analysis is to identify
      relevant genomic features as well as build up a predictive model based on
      selected features for various tasks such as personalized medicine. Correlating
      the large number of 'omics' features with a certain phenotype is particularly
      challenging due to small sample size (n) and high dimensionality (p). To address
      this small n, large p problem, various forms of sparse regression models have
      been proposed by exploiting the sparsity assumption. Among these, network
      constrained sparse regression model is of particular interest due to its ability
      to utilize the prior graph/network structure in the omics data. Despite its
      potential usefulness for omics data analysis, no efficient R implementation is
      publicly available. Here we present an R software package 'glmgraph' that
      implements the graph-constrained regularization for both sparse linear regression
      and sparse logistic regression. We implement both the L1 penalty and minimax
      concave penalty for variable selection and Laplacian penalty for coefficient
      smoothing. Efficient coordinate descent algorithm is used to solve the
      optimization problem. We demonstrate the use of the package by applying it to a
      human microbiome dataset, where phylogeny structure among bacterial taxa is
      available. AVAILABILITY AND IMPLEMENTATION: 'glmgraph' is implemented in R and
      C++ Armadillo and publicly available under CRAN.

PMID- 26315910
TI  - Identification of hierarchical chromatin domains.
AB  - MOTIVATION: The three-dimensional structure of the genome is an important
      regulator of many cellular processes including differentiation and gene
      regulation. Recently, technologies such as Hi-C that combine proximity ligation
      with high-throughput sequencing have revealed domains of self-interacting
      chromatin, called topologically associating domains (TADs), in many organisms.
      Current methods for identifying TADs using Hi-C data assume that TADs are non
      overlapping, despite evidence for a nested structure in which TADs and sub-TADs
      form a complex hierarchy. RESULTS: We introduce a model for decomposition of
      contact frequencies into a hierarchy of nested TADs. This model is based on
      empirical distributions of contact frequencies within TADs, where positions that
      are far apart have a greater enrichment of contacts than positions that are close
      together. We find that the increase in contact enrichment with distance is
      stronger for the inner TAD than for the outer TAD in a TAD/sub-TAD pair. Using
      this model, we develop the TADtree algorithm for detecting hierarchies of nested
      TADs. TADtree compares favorably with previous methods, finding TADs with a
      greater enrichment of chromatin marks such as CTCF at their boundaries.
      AVAILABILITY AND IMPLEMENTATION: A python implementation of TADtree is available
      at http://compbio.cs.brown.edu/software/ CONTACT: braphael@cs.brown.edu
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 26315911
TI  - msa: an R package for multiple sequence alignment.
AB  - Although the R platform and the add-on packages of the Bioconductor project are
      widely used in bioinformatics, the standard task of multiple sequence alignment
      has been neglected so far. The msa package, for the first time, provides a
      unified R interface to the popular multiple sequence alignment algorithms
      ClustalW, ClustalOmega and MUSCLE. The package requires no additional software
      and runs on all major platforms. Moreover, the msa package provides an R
      interface to the powerful package shade which allows for flexible and
      customizable plotting of multiple sequence alignments. AVAILABILITY AND
      IMPLEMENTATION: msa is available via the Bioconductor project:
      http://bioconductor.org/packages/release/bioc/html/msa.html. Further information
      and the R code of the example presented in this paper are available at
      http://www.bioinf.jku.at/software/msa/.

PMID- 26315912
TI  - Hierarchical boosting: a machine-learning framework to detect and classify hard
      selective sweeps in human populations.
AB  - MOTIVATION: Detecting positive selection in genomic regions is a recurrent topic
      in natural population genetic studies. However, there is little consistency among
      the regions detected in several genome-wide scans using different tests and/or
      populations. Furthermore, few methods address the challenge of classifying
      selective events according to specific features such as age, intensity or state
      (completeness). RESULTS: We have developed a machine-learning classification
      framework that exploits the combined ability of some selection tests to uncover
      different polymorphism features expected under the hard sweep model, while
      controlling for population-specific demography. As a result, we achieve high
      sensitivity toward hard selective sweeps while adding insights about their
      completeness (whether a selected variant is fixed or not) and age of onset. Our
      method also determines the relevance of the individual methods implemented so far
      to detect positive selection under specific selective scenarios. We calibrated
      and applied the method to three reference human populations from The 1000 Genome
      Project to generate a genome-wide classification map of hard selective sweeps.
      This study improves detection of selective sweep by overcoming the classical
      selection versus no-selection classification strategy, and offers an explanation
      to the lack of consistency observed among selection tests when applied to real
      data. Very few signals were observed in the African population studied, while our
      method presents higher sensitivity in this population demography. AVAILABILITY
      AND IMPLEMENTATION: The genome-wide results for three human populations from The
      1000 Genomes Project and an R-package implementing the 'Hierarchical Boosting'
      framework are available at http://hsb.upf.edu/.

PMID- 26315913
TI  - HapCol: accurate and memory-efficient haplotype assembly from long reads.
AB  - MOTIVATION: Haplotype assembly is the computational problem of reconstructing
      haplotypes in diploid organisms and is of fundamental importance for
      characterizing the effects of single-nucleotide polymorphisms on the expression
      of phenotypic traits. Haplotype assembly highly benefits from the advent of
      'future-generation' sequencing technologies and their capability to produce long
      reads at increasing coverage. Existing methods are not able to deal with such
      data in a fully satisfactory way, either because accuracy or performances degrade
      as read length and sequencing coverage increase or because they are based on
      restrictive assumptions. RESULTS: By exploiting a feature of future-generation
      technologies-the uniform distribution of sequencing errors-we designed an exact
      algorithm, called HapCol, that is exponential in the maximum number of
      corrections for each single-nucleotide polymorphism position and that minimizes
      the overall error-correction score. We performed an experimental analysis,
      comparing HapCol with the current state-of-the-art combinatorial methods both on
      real and simulated data. On a standard benchmark of real data, we show that
      HapCol is competitive with state-of-the-art methods, improving the accuracy and
      the number of phased positions. Furthermore, experiments on realistically
      simulated datasets revealed that HapCol requires significantly less computing
      resources, especially memory. Thanks to its computational efficiency, HapCol can
      overcome the limits of previous approaches, allowing to phase datasets with
      higher coverage and without the traditional all-heterozygous assumption.
      AVAILABILITY AND IMPLEMENTATION: Our source code is available under the terms of
      the GNU General Public License at http://hapcol.algolab.eu/ CONTACT:
      bonizzoni@disco.unimib.it SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 26315914
TI  - CoD: inferring immune-cell quantities related to disease states.
AB  - MOTIVATION: The immune system comprises a complex network of genes, cells and
      tissues, coordinated through signaling pathways and cell-cell communications.
      However, the orchestrated role of the multiple immunological components in
      disease is still poorly understood. Classifications based on gene-expression data
      have revealed immune-related signaling pathways in various diseases, but how such
      pathways describe the immune cellular physiology remains largely unknown.
      RESULTS: We identify alterations in cell quantities discriminating between
      disease states using ' Cell type of Disease' (CoD), a classification-based
      approach that relies on computational immune-cell decomposition in gene
      expression datasets. CoD attains significantly higher accuracy than alternative
      state-of-the-art methods. Our approach is shown to recapitulate and extend
      previous knowledge acquired with experimental cell-quantification technologies.
      CONCLUSIONS: The results suggest that CoD can reveal disease-relevant cell types
      in an unbiased manner, potentially heralding improved diagnostics and treatment.
      AVAILABILITY AND IMPLEMENTATION: The software described in this article is
      available at http://www.csgi.tau.ac.il/CoD/.

PMID- 26315915
TI  - Integrated structure- and ligand-based in silico approach to predict inhibition
      of cytochrome P450 2D6.
AB  - MOTIVATION: Cytochrome P450 (CYP) is a superfamily of enzymes responsible for the
      metabolism of drugs, xenobiotics and endogenous compounds. CYP2D6 metabolizes
      about 30% of drugs and predicting potential CYP2D6 inhibition is important in
      early-stage drug discovery. RESULTS: We developed an original in silico approach
      for the prediction of CYP2D6 inhibition combining the knowledge of the protein
      structure and its dynamic behavior in response to the binding of various ligands
      and machine learning modeling. This approach includes structural information for
      CYP2D6 based on the available crystal structures and molecular dynamic
      simulations (MD) that we performed to take into account conformational changes of
      the binding site. We performed modeling using three learning algorithms--support
      vector machine, RandomForest and NaiveBayesian--and we constructed combined
      models based on topological information of known CYP2D6 inhibitors and predicted
      binding energies computed by docking on both X-ray and MD protein conformations.
      In addition, we identified three MD-derived structures that are capable all
      together to better discriminate inhibitors and non-inhibitors compared with
      individual CYP2D6 conformations, thus ensuring complementary ligand profiles.
      Inhibition models based on classical molecular descriptors and predicted binding
      energies were able to predict CYP2D6 inhibition with an accuracy of 78% on the
      training set and 75% on the external validation set.

PMID- 26315916
TI  - Characterising knee motion and laxity in a testing machine for application to
      total knee evaluation.
AB  - The goal of this study was to determine knee motions in specimens under combined
      input forces over a full range of flexion, so that the various flexion angles and
      loading combinations encountered in functional conditions would be contained. The
      purpose was that the data would act as a benchmark for the evaluation of TKR
      designs using the same testing methodology. We measured the neutral path of
      motion and laxity about the neutral path. The femur was flexed in a continuous
      movement, rather than at discrete flexion angles, using optical tracking. The
      motion of the femoral circular axis relative to the tibia was determined, as well
      as the contact patches on the tibial surfaces. The neutral path of motion was
      independent of compressive load, and consisted of a relatively constant medial
      contact and steady posterior displacement laterally, in agreement with previous
      studies. The anterior-posterior laxities of the lateral and medial condyles were
      similar whether AP forces or torques were applied. The lateral laxity was
      predominantly anterior with respect to the neutral path, while on the medial
      side, the laxity was less than lateral and predominantly posterior of the neutral
      path. Contact on the anterior surface of the medial tibial plateau only occurred
      in some cases in 5 degrees  hyperextension and at 0 degrees  flex when an
      anterior femoral shear or an external femoral torque were applied. The method can
      be regarded as a development of the ASTM constraint standard, with the addition
      of the benchmark, for the evaluation of total knee designs. 

PMID- 26315917
TI  - Unlocking the talus by eversion limits medial ankle injury risk during external
      rotation.
AB  - Eversion prior to excessive external foot rotation has been shown to predispose
      the anterior tibiofibular ligament (ATiFL) to failure, yet protect the anterior
      deltoid ligament (ADL) from failure despite high levels of foot rotation. The
      purpose of the current study was to measure the rotations of both the subtalar
      and talocrural joints during foot external rotation at sub-failure levels in
      either a neutral or a pre-everted position as a first step towards understanding
      the mechanisms of injury in previous studies. Fourteen (seven pairs) cadaver
      lower extremities were externally rotated 20 degrees  in either a pre-everted or
      neutral configuration, without producing injury. Motion capture was performed to
      track the tibia, talus, and calcaneus motions, and a joint coordinate system was
      used to analyze motions of the two joints. While talocrural joint rotation was
      greater in the neutral ankle (13.3+/-2.0 degrees  versus 10.5+/-2.7 degrees ,
      p=0.006), subtalar joint rotation was greater in the pre-everted ankle (2.4+/-1.9
      degrees  versus 1.1+/-1.0 degrees , p=0.014). Overall, the talocrural joint
      rotated more than the subtalar joint (11.9+/-2.8 degrees  versus 1.8+/-1.6
      degrees , p<0.001). It was proposed that the calcaneus and talus 'lock' in a
      neutral position, but 'unlock' when the ankle is everted prior to rotation. This
      locking/unlocking mechanism could be responsible for an increased subtalar
      rotation, but decreased talocrural rotation when the ankle is pre-everted,
      protecting the ADL from failure. This study may provide information valuable to
      the study of external rotation kinematics and injury risk. 

PMID- 26315918
TI  - Kinetic comparison of walking on a treadmill versus over ground in children with
      cerebral palsy.
AB  - Kinetic outcomes are an essential part of clinical gait analysis, and can be
      collected for many consecutive strides using instrumented treadmills. However,
      the validity of treadmill kinetic outcomes has not been demonstrated for children
      with cerebral palsy (CP). In this study we compared ground reaction forces (GRF),
      center of pressure, and hip, knee and ankle moments, powers and work, between
      overground (OG) and self-paced treadmill (TM) walking for 11 typically developing
      (TD) children and 9 children with spastic CP. Considerable differences were found
      in several outcome parameters. In TM, subjects demonstrated lower ankle power
      generation and more absorption, and increased hip moments and work. This shift
      from ankle to hip strategy was likely due to a more backward positioning of the
      hip and a slightly more forward trunk lean. In mediolateral direction, GRF and
      hip and knee joint moments were increased in TM due to wider step width. These
      findings indicate that kinetic data collected on a TM cannot be readily compared
      with OG data in TD children and children with CP, and that treadmill-specific
      normative data sets should be used when performing kinetic gait analysis on a
      treadmill. 

PMID- 26315919
TI  - Sensitivity of femoral strain calculations to anatomical scaling errors in
      musculoskeletal models of movement.
AB  - The determination of femoral strain in post-menopausal women is important for
      studying bone fragility. Femoral strain can be calculated using a reference
      musculoskeletal model scaled to participant anatomies (referred to as scaled
      generic) combined with finite-element models. However, anthropometric errors
      committed while scaling affect the calculation of femoral strains. We assessed
      the sensitivity of femoral strain calculations to scaled-generic anthropometric
      errors. We obtained CT images of the pelves and femora of 10 healthy post
      menopausal women and collected gait data from each participant during six weight
      bearing tasks. Scaled-generic musculoskeletal models were generated using skin
      mounted marker distances. Image-based models were created by modifying the scaled
      generic models using muscle and joint parameters obtained from the CT data.
      Scaled-generic and image-based muscle and hip joint forces were determined by
      optimisation. A finite-element model of each femur was generated from the CT
      images, and both image-based and scaled-generic principal strains were computed
      in 32 regions throughout the femur. The intra-participant regional RMS error
      increased from 380 MUepsilon (R2=0.92, p<0.001) to 4064 MUepsilon (R2=0.48,
      p<0.001), representing 5.2% and 55.6% of the tensile yield strain in bone,
      respectively. The peak strain difference increased from 2821 MUepsilon in the
      proximal region to 34,166 MUepsilon at the distal end of the femur. The inter
      participant RMS error throughout the 32 femoral regions was 430 MUepsilon
      (R2=0.95, p<0.001), representing 5.9% of bone tensile yield strain. We conclude
      that scaled-generic models can be used for determining cohort-based averages of
      femoral strain whereas image-based models are better suited for calculating
      participant-specific strains throughout the femur.

PMID- 26315920
TI  - The influence of the instabilities in modelling arteriovenous junction
      haemodynamics.
AB  - The arteriovenous junction is characterised by high flow rates, large pressure
      difference and typically a palpable thrill or audible bruit, associated with
      turbulent flow. However, the arteriovenous junction is frequently studied with
      the assumption of streamline flow. This assumption is based on the Reynolds
      number calculation, although other factors can contribute to turbulent
      generation. In this study, the presence of instabilities is examined and the
      influencing factors discussed. This was performed using a pseudo-realistic
      geometry with adapted graft angles, vein diameter, outflow split ratio and graft
      inlet velocity values. Correlation was performed between steady and unsteady
      averaged simulation cases with correlation performance ranked. Overall the
      arteriovenous junction is capable of possessing highly disturbed flows, in which
      strict modelling requirements are necessary to capture such instabilities and
      avoid erroneous conclusions. Vein diameter and flow split ratio contribute to
      turbulent generation, thus Reynolds number cannot be used as a sole turbulent
      criterion in the arteriovenous junction. 

PMID- 26315921
TI  - Determining the combined effect of the lymphatic valve leaflets and sinus on
      resistance to forward flow.
AB  - The lymphatic system is vital to a proper maintenance of fluid and solute
      homeostasis. Collecting lymphatics are composed of actively contracting tubular
      vessels segmented by bulbous sinus regions that encapsulate bi-leaflet check
      valves. Valve resistance to forward flow strongly influences pumping performance.
      However, because of the sub-millimeter size of the vessels with flow rates
      typically <1 ml/h and pressures of a few cmH2O, resistance is difficult to
      measure experimentally. Using a newly defined idealized geometry, we employed an
      uncoupled approach where the solid leaflet deflections of the open valve were
      computed and lymph flow calculations were subsequently performed. We sought to
      understand: 1) the effect of sinus and leaflet size on the resulting deflections
      experienced by the valve leaflets and 2) the effects on valve resistance to
      forward flow of the fully open valve. For geometries with sinus-to-root diameter
      ratios >1.39, the average resistance to forward flow was 0.95*10(6)[g/(cm4 s)].
      Compared to the viscous pressure drop that would occur in a straight tube the
      same diameter as the upstream lymphangion, valve leaflets alone increase the
      pressure drop up to 35%. However, the presence of the sinus reduces viscous
      losses, with the net effect that when combined with leaflets the overall
      resistance is less than that of the equivalent continuing straight tube.
      Accurately quantifying resistance to forward flow will add to the knowledge used
      to develop therapeutics for treating lymphatic disorders and may eventually lead
      to understanding some forms of primary lymphedema.

PMID- 26315922
TI  - Antimicrobial photodynamic effect of phenothiazinic photosensitizers in
      formulations with ethanol on Pseudomonas aeruginosa biofilms.
AB  - BACKGROUND DATA: Methylene blue (MB) and toluidine blue (TB) are recognized as
      safe photosensitizers (Ps) for use in humans. The clinical effectiveness of the
      antimicrobial photodynamic therapy with MB and TB needs to be optimized, and
      ethanol can increase their antimicrobial effect. Formulations of MB and TB
      containing ethanol were evaluated for their ability to produce singlet oxygen and
      their antibacterial effect on Pseudomonas aeruginosa biofilms. METHODS:
      Photoactivated formulations were prepared by diluting the Ps (250 MUM) in
      buffered water (pH 5.6, sodium acetate/acetic acid), 10% ethanol (buffer:
      ethanol, 90:10), or 20% ethanol (buffer: ethanol, 80:20). Biofilms also were
      exposed to the buffer, 10% ethanol, or 20% ethanol without photoactivation.
      Untreated biofilm was considered the control group. The production of singlet
      oxygen in the formulations was measured based on the photo-oxidation of 1,3
      diphenylisobenzofuran. The photo-oxidation and CFU (log10) data were evaluated by
      two-way ANOVA and post-hoc Tukey's tests. RESULTS: In all the formulations,
      compared to TB, MB showed higher production of singlet oxygen. In the absence of
      photoactivation, neither the buffer nor the 10% ethanol solution showed any
      antimicrobial effect, while the 20% ethanol solution significantly reduced
      bacterial viability (P=0.009). With photoactivation, only the formulations
      containing MB and both 10% and 20% ethanol solutions significantly reduced the
      viability of P. aeruginosa biofilms when compared with the control. CONCLUSIONS:
      MB formulations containing ethanol enhanced the antimicrobial effect of the
      photodynamic therapy against P. aeruginosa biofilms in vitro.

PMID- 26315923
TI  - In vitro photoinactivation of bovine mastitis related pathogens.
AB  - BACKGROUND: Bovine mastitis is considered the most important disease of worldwide
      dairy industry. Treatment of this disease is based on the application
      intramammary antibiotic, which favors an increase in the number of resistant
      bacteria in the last decade. Photodynamic inactivation (PDI) has been
      investigated in different areas of Health Sciences, and has shown great potential
      for inactivating different pathogens, without any selection of resistant
      microorganisms. The objective of this study was to investigate the efficacy of
      PDI in the inactivation of pathogens associated with bovine mastitis. METHODS: We
      tested the effectiveness of PDI against antibiotic resistant strains, isolated
      from bovine mastitis, from the following species: Staphylococcus aureus,
      Streptococcus agalactiae, Streptococcus dysgalactiae, Corynebacterium bovis, and
      the alga Prototheca zopfii. Nine experimental groups were evaluated: control, no
      treatment; light only, irradiation of a red light-emitting diode (lambda=662 (20)
      nm) for 180 s; exposure to 50 MUM methylene blue alone for 5 min; and PDI for 5,
      10, 30, 60, 120 and 180 s. RESULTS: S. dysgalactiae, S. aureus, and C. bovis were
      inactivated after 30s of irradiation, whereas S. agalactiae was inactivated after
      120 s and P. zopfii at 180 s of irradiation. CONCLUSION: These results show that
      PDI can be an interesting tool for inactivating pathogens for bovine mastitis.

PMID- 26315924
TI  - Preparation of a silanone through oxygen atom transfer to a stable cyclic
      silylene.
AB  - We report the evaporation of a stable cyclic silylene and its oxidation (with
      ozone or N2 O) through oxygen atom transfer to form the corresponding silanone
      under matrix isolation conditions. As uncomplexed silanones are rare owing to
      their very high reactivity, this method provides an alternative route to these
      sought-after molecules. The silanone, as well as a novel bicyclic silane with a
      bridgehead silicon atom derived from an intramolecular silylene C?H bond
      insertion, were characterized by comparison of high-resolution infrared spectra
      with density functional theory (DFT) computations at the M06-2X/cc-pVDZ level of
      theory. 

PMID- 26315925
TI  - Diagnostic tools for post-gastric bypass hypoglycaemia.
AB  - In spite of its evident success, several late complications can occur after
      gastric bypass surgery. One of these is post-gastric bypass hypoglycaemia. No
      evidence-based guidelines exist in the literature on how to confirm the presence
      of this syndrome. This study aims to describe and compare the tests aimed at
      making a diagnosis of post-gastric bypass hypoglycaemia and to provide a
      diagnostic approach based upon the available evidence. A search was conducted in
      PubMed, Cochrane and Embase. A few questionnaires have been developed to measure
      the severity of symptoms in post-gastric bypass hypoglycaemia but none has been
      validated. The gold standard for provocation of a hypoglycaemic event is the oral
      glucose tolerance test or the liquid mixed meal tolerance test. Both show a high
      prevalence of hypoglycaemia in post-gastric bypass patients with and without
      hypoglycaemic complaints as well as in healthy volunteers. No uniformly
      established cut-off values for glucose concentrations are defined in the
      literature for the diagnosis of post-gastric bypass hypoglycaemia. For
      establishing an accurate diagnosis of post-gastric bypass hypoglycaemia, a
      validated questionnaire, in connection with the diagnostic performance of
      provocation tests, is the most important thing missing. Given these shortcomings,
      we provide recommendations based upon the current literature. 

PMID- 26315926
TI  - Successful treatment of self-inflicted tongue trauma patient using a special oral
      appliance.
AB  - A 7-year-old male presented with a painful ulcerative lesion on the right lateral
      tongue and left lower buccal mucosa due to self-inflicted trauma. Antibiotic
      medication and use of a mouthwash agent were not effective. We made a special
      oral appliance to cover the maxillary arch and teeth to protect the tongue. The
      patient showed immediate improvement and did not suffer from any complications.
      Invasive procedures such as biopsy were not needed. We believe that accurate
      clinical diagnosis is important and treatment with an oral appliance is effective
      in self-inflicted oral trauma in children. 

PMID- 26315927
TI  - To remove or not to remove: Review of cases of medial migration of tympanostomy
      tubes.
AB  - OBJECTIVE: Few cases of medial migration of tympanostomy tubes have been reported
      and its optimal management has not been well delineated especially in
      asymptomatic patients. The aim of this review is to present all cases of
      medialized tympanostomy tubes reported in the literature in order to provide the
      most beneficial management option. METHODS: Eligible articles were identified
      through a comprehensive search in Cochrane, Embase and Medline electronic
      databases. Two reviewers independently screened the data sources, using pre
      defined inclusion criteria to generate a list of eligible articles. Data
      extracted included patient demographics, diagnosis, type of tube, timing of
      migration, presenting symptoms, examination outcomes, treatment and follow up.
      RESULTS: 10 articles were chosen for data extraction from which 29 patients
      presenting with medial migration of tympanostomy tube were identified.
      CONCLUSION: The low complications associated with removing a medialized tube and
      the risk of leaving foreign objects in the middle ear cleft make myringotomy for
      removal of the tube a practical and safe management option for medialized tubes
      even in asymptomatic patients.

PMID- 26315928
TI  - Impact of socio-economic status on ear health and behaviour in children: A cross
      sectional study in the capital of India.
AB  - INTRODUCTION: Socio-economic differences in the society have been a major cause
      for the discrepancy in disease and behavioural patterns in society. With 360
      million people (32 million children) in the world suffering from disabling
      hearing losses, it is imperative to gain an insight into the impact of
      differences in socio-economic strata on children's ear health issues, their
      knowledge of ear ailments and attitude towards ear health so as to suggest
      policies addressing ear health issues. METHODS: The study was carried out in two
      different school types namely government schools and private schools which
      represent wide difference in the socio-economic status of the students studying
      there. A questionnaire was administered to students aged 10 to 13 years to assess
      the current ear care practices, knowledge regarding ear ailments, attitude
      towards hearing and their adaptability to reform. RESULTS: The children belonging
      to higher socio-economic status were found to have lesser incidence of ear
      diseases and ear abuse, more referrals for ear ailments, lesser indulgence in
      risky ear health behaviours, better knowledge pool, positive attitude towards ear
      health and hearing and were more adaptable to change for better hearing.
      CONCLUSION: Structures of social disparity are essential determinants of ear
      health acting both independently and through their influence on behavioural
      determinants of health. Increasing awareness of ear health issues at the school
      level itself should be one of the goals of health care providers.

PMID- 26315929
TI  - Predictors of complications following adenotonsillectomy in children with severe
      obstructive sleep apnea.
AB  - OBJECTIVE: To identify pre-operative risk factors predicting complications
      following adenotonsillectomy in children with severe OSA. METHODS: Retrospective
      chart review in an academic tertiary care center. Children with symptoms of OSA
      with overnight polysomnography (PSG) revealing apnea-hypopnea index (AHI) >10,
      who underwent adenotonsillectomy with overnight postoperative observation between
      2008 and 2012. Univariate logistic regression was used to assess odds ratio (OR)
      of individual risk factors versus postoperative complications such as overnight
      desaturations <90%, length of stay (LOS)>24 h, supplemental oxygen requirement,
      and transfer to a higher level of care. RESULTS: All patients (n=157) with severe
      OSA were observed overnight. Mean age was 5.3+/-3.7 years. Twenty-five (15.9%)
      patients had LOS>24 h. Forty-two (26.8%) had overnight desaturations <90%. AHI
      >=15 and O2 saturation nadir <80% on preop polysomnography (PSG) were independent
      predictors of post-op O2 saturation <90% and LOS>24 h. (p<0.05). PSG minimum
      saturation <80% was the strongest predictor of all variables examined with an OR
      of 6.98 (3.15-15.48, 95% CI) for desaturation <90% and 5.19 (2.11-12.75, 95% CI)
      for LOS>24 h. Preop PSG O2 saturation<90% predicted overnight post op oxygen
      requirement with an OR of 3.38 (1.39-8.25, 95%CI). CONCLUSIONS: Preoperative
      polysomnography yields significant independent predictors of post-op
      complications in children with OSA. While AHI is a significant independent
      predictor, minimum O2 saturation on preop PSG appeared the strongest predictor
      when <80%. Patients with these risk factors, especially low O2 on PSG, warrant
      overnight observation with continuous pulse oximetry.

PMID- 26315930
TI  - Paroxysmal nocturnal hemoglobinuria and telomere length predicts response to
      immunosuppressive therapy in pediatric aplastic anemia.
AB  - Acquired aplastic anemia is an immune-mediated disease characterized by severe
      defects in stem cell number resulting in hypocellular marrow and peripheral blood
      cytopenias. Minor paroxysmal nocturnal hemoglobinuria populations and a short
      telomere length were identified as predictive biomarkers of immunosuppressive
      therapy responsiveness in aplastic anemia. We enrolled 113 aplastic anemia
      patients (63 boys and 50 girls) in this study to evaluate their response to
      immunosuppressive therapy. The paroxysmal nocturnal hemoglobinuria populations
      and telomere length were detected by flow cytometry. Forty-seven patients (42%)
      carried a minor paroxysmal nocturnal hemoglobinuria population. The median
      telomere length of aplastic anemia patients was -0.99 standard deviation (SD)
      (range -4.01-+3.01 SD). Overall, 60 patients (53%) responded to immunosuppressive
      therapy after six months. Multivariate logistic regression analysis identified
      the absence of a paroxysmal nocturnal hemoglobinuria population and a shorter
      telomere length as independent unfavorable predictors of immunosuppressive
      therapy response at six months. The cohort was stratified into a group of poor
      prognosis (paroxysmal nocturnal hemoglobinuria negative and shorter telomere
      length; 37 patients) and good prognosis (paroxysmal nocturnal hemoglobinuria
      positive and/or longer telomere length; 76 patients), respectively. The response
      rates of the poor prognosis and good prognosis groups at six months were 19% and
      70%, respectively (P<0.001). The combined absence of a minor paroxysmal nocturnal
      hemoglobinuria population and a short telomere length is an efficient predictor
      of poor immunosuppressive therapy response, which should be considered while
      deciding treatment options: immunosuppressive therapy or first-line hematopoietic
      stem cell transplantation. The trial was registered in www.umin.ac.jp with number
      UMIN000017972. 

PMID- 26315931
TI  - Outcome of advanced chronic lymphocytic leukemia following different first-line
      and relapse therapies: a meta-analysis of five prospective trials by the German
      CLL Study Group (GCLLSG).
AB  - To evaluate the effect of first-line and subsequent therapies, the outcome of
      1,558 patients with chronic lymphocytic leukemia from five prospective phase
      II/III trials conducted between 1999 and 2010 was analyzed. The 3-year overall
      survival rate was higher after first-line treatment with chemoimmunotherapies
      such as fludarabine/cyclophosphamide/rituximab (87.9%) or bendamustine/rituximab
      (90.7%) compared to chemotherapies without an antibody
      (fludarabine/cyclophosphamide: 84.6%; fludarabine: 77.5%; chlorambucil: 77.4%).
      Furthermore, the median overall survival was longer in patients receiving at
      least one antibody-containing regimen in any treatment line (94.4 months)
      compared to the survival in patients who never received an antibody (84.3 months,
      P<0.0001). Univariate Cox regression analysis demonstrated that patients who did
      receive antibody treatment had a 1.42-fold higher risk of death (hazard ratio,
      1.42; 95% confidence interval: 1.185-1.694). Therapies administered at relapse
      were very heterogeneous. Only 55 of 368 patients (14.9%) who started second-line
      treatment >24 months after first-line therapy repeated the first-line regimen.
      Among 315 patients requiring treatment <=24 months after first-line therapy,
      cyclophosphamide/doxorubicin/vincristine/prednisone with or without rituximab as
      well as alemtuzumab were the most commonly used therapies. In these early
      relapsing patients, the median overall survival was shorter following therapies
      containing an anthracycline and/or three or more cytotoxic agents (e.g.
      cyclophosphamide/doxorubicin/vincristine/prednisone or
      fludarabine/cyclophosphamide/mitoxantrone, 30.0 months) compared to single agent
      chemotherapy (e.g. fludarabine; 39.6 months) and standard chemoimmunotherapy
      (e.g. fludarabine/cyclophosphamide/rituximab: 61.6 months). In conclusion, the
      analysis confirms the superior efficacy of chemoimmunotherapies in patients with
      chronic lymphocytic leukemia. Moreover, the use of aggressive
      chemo(immuno)therapy combinations in patients with an early relapse does not
      offer any benefit when compared to less intensive therapies. Trial identifier:
      NCT00281918, ISRCTN75653261, ISRCTN36294212, NCT00274989 and NCT00147901.

PMID- 26315932
TI  - Impairment of neutrophil oxidative burst in children with sickle cell disease is
      associated with heme oxygenase-1.
AB  - Sickle cell disease is a risk factor for invasive bacterial infections, and
      splenic dysfunction is believed to be the main underlying cause. We have
      previously shown that the liberation of heme in acute hemolysis can induce heme
      oxygenase-1 during granulopoiesis, impairing the ability of developing
      neutrophils to mount a bactericidal oxidative burst, and increasing
      susceptibility to bacterial infection. We hypothesized that this may also occur
      with the chronic hemolysis of sickle cell disease, potentially contributing to
      susceptibility to infections. We found that neutrophil oxidative burst activity
      was significantly lower in treatment-naive children with sickle cell disease
      compared to age-, gender- and ethnicity-matched controls, whilst degranulation
      was similar. The defect in neutrophil oxidative burst was quantitatively related
      to both systemic heme oxygenase-1 activity (assessed by carboxyhemoglobin
      concentration) and neutrophil mobilization. A distinct population of heme
      oxygenase-1-expressing cells was present in the bone marrow of children with
      sickle cell disease, but not in healthy children, with a surface marker profile
      consistent with neutrophil progenitors (CD49d(Hi) CD24(Lo) CD15(Int) CD16(Int)
      CD11b(+/-)). Incubation of promyelocytic HL-60 cells with the heme oxygenase-1
      substrate and inducer, hemin, demonstrated that heme oxygenase-1 induction during
      neutrophilic differentiation could reduce oxidative burst capacity. These
      findings indicate that impairment of neutrophil oxidative burst activity in
      sickle cell disease is associated with hemolysis and heme oxygenase-1 expression.
      Neutrophil dysfunction might contribute to risk of infection in sickle cell
      disease, and measurement of neutrophil oxidative burst might be used to identify
      patients at greatest risk of infection, who might benefit from enhanced
      prophylaxis. 

PMID- 26315933
TI  - Ten-Year Trends (2000-2010) of Overweight and Obesity Prevalence among the Young
      and Middle-Aged Adult Population of the Balearic Islands, a Mediterranean Region.
AB  - BACKGROUND AND AIMS: This article aimed at assessing the 10-year trends (2000
      2010) in the prevalence of overweight and obesity among the Balearic Islands'
      adult population. METHODS: Body mass index (BMI, kg/m2) for young (18-35 year
      olds) and middle-aged (36-55 year-olds) adults living in the Balearics was
      calculated. Data represented 1,089 people during 1999-2000 and 1,081 people
      during 2009-2010. The BMI categories were as follows: normal weight (18.5 < 25),
      overweight (25.0 < 30) and obese (>=30). RESULTS: Weighted frequency estimates
      and logistic regression analysis were used to calculate overweight and obesity
      trends. While the prevalence of overweight and obesity mostly remained stable
      over the 2000-2010 period, the prevalence of obesity increased from 5.1 to 8.3%
      in young adults (aged 18-35), a 1.66-fold increase in prevalence (95% CI 1.02
      2.70) over the study period. CONCLUSIONS: Total overweight and obesity prevalence
      remained stable in the Balearic adult population; however, a rising prevalence of
      obesity has been observed in young adults, which suggests a need to develop and
      change current strategies in order to reverse the current trends in obesity among
      this age group.

PMID- 26315934
TI  - A systematic review of attention deficit hyperactivity disorder (ADHD) and
      mathematical ability: current findings and future implications.
AB  - BACKGROUND: Several recent behavioural and behavioural genetic studies have
      investigated the relationship between attention deficit hyperactivity disorder
      (ADHD) and mathematical ability. The aim of this systematic review was to provide
      an overview of these studies to date. An emphasis was placed on reviewing results
      that explored the association between mathematics and the two ADHD components of
      attention and hyperactivity-impulsivity separately. METHODS: A systematic search
      of quantitative studies investigating the association between mathematics and
      ADHD was conducted across five databases (PsychINFO, Web of Science, PubMed,
      EMBASE, and Scopus). A total of 30 cross-sectional and four longitudinal studies
      were included in this review. RESULTS: Narrative synthesis of the results was
      provided using PRISMA guidelines. Taken together, the studies pointed at
      substantial evidence for a negative association between ADHD symptoms and
      mathematical ability. This association was particularly marked for the
      inattentive component of ADHD than for the hyperactive-impulsive component.
      Evidence from twin studies also showed a significant genetic correlation between
      mathematics and ADHD, which was greater for the inattentive component of ADHD
      compared to the hyperactive-impulsive component. CONCLUSIONS: The differential
      relationship of the hyperactivity-impulsivity and inattention domains with
      mathematics emphasises the heterogeneity within the disorder and suggests a
      partially different aetiology of the two ADHD domains. A better understanding of
      the aetiology of ADHD could help develop more efficient interventions aimed at
      the reduction of its symptoms. It could also offer an explanatory framework for
      shortcomings in achievement and inform the development of non-pharmacological
      intervention strategies.

PMID- 26315935
TI  - Toward Balance Recovery With Leg Prostheses Using Neuromuscular Model Control.
AB  - OBJECTIVE: Lower limb amputees are at high risk of falling as current prosthetic
      legs provide only limited functionality for recovering balance after unexpected
      disturbances. For instance, the most established control method used on powered
      leg prostheses tracks local joint impedance functions without taking the global
      function of the leg in balance recovery into account. Here, we explore an
      alternative control policy for powered transfemoral prostheses that considers the
      global leg function and is based on a neuromuscular model of human locomotion.
      METHODS: We adapt this model to describe and simulate an amputee walking with a
      powered prosthesis using the proposed control, and evaluate the gait robustness
      when confronted with rough ground and swing leg disturbances. We then implement
      and partially evaluate the resulting controller on a leg prosthesis prototype
      worn by a nonamputee user. RESULTS: In simulation, the proposed prosthesis
      control leads to gaits that are more robust than those obtained by the impedance
      control method. The initial hardware experiments with the prosthesis prototype
      show that the proposed control reproduces normal walking patterns qualitatively
      and effectively responds to disturbances in early and late swing. However, the
      response to midswing disturbances neither replicates human responses nor averts
      falls. CONCLUSIONS: The neuromuscular model control is a promising alternative to
      existing prosthesis controls, although further research will need to improve on
      the initial implementation and determine how well these results transfer to
      amputee gait. SIGNIFICANCE: This paper provides a potential avenue for future
      development of control policies that help to improve amputee balance recovery.

PMID- 26315936
TI  - Electrolyte-gated graphene Schottky barrier transistors.
AB  - A new device architecture for flexible vertical Schottky barrier (SB) transistors
      and logic gates based on graphene-organic-semiconductor-metal heterostructures
      and ion gel gate dielectrics is demonstrated. The devices show well-behaved p-
      and n-type characteristics under low-voltage operation (<1 V), yielding high
      current densities (>100 mA cm(-2) ) and on/off current ratios (>10(3) ). 

PMID- 26315938
TI  - Anti-Porphyromonas gingivalis Antibodies in Rheumatoid Arthritis: Comment on the
      Article by Seror et al.

PMID- 26315939
TI  - Multifaceted roles of 5'-regulatory region of the cancer associated gene B4GALT1
      and its comparison with the gene family.
AB  - beta1,4-Galactosylransferases are a family of enzymes encoded by seven B4GALT
      genes and are involved in the development of anticancer drug resistance and
      metastasis. Among these genes, the B4GALT1 shows significant variations in the
      transcript origination sites in different cell types/tissues and encodes an
      interesting dually partitioning beta-1, 4-galactosyltransferase protein. We
      identified at 5'-end of B4GALT1 a 1.454 kb sequence forming a transcription
      regulatory region, referred to by us as the TR1-PE1, had all characteristics of a
      bidirectional promoter directing the transcription of B4GALT1 in a divergent
      manner along with its long non-coding RNA (lncRNA) antisense counterpart B4GALT1
      AS1. The TR1-PE1 showed unique dinucleotide base-stacking energy values specific
      to transcription factor binding sites (TFBSs), INR and BRE, and harbored CpG
      Island (CGI) that showed GC skew with potential for R-loop formation at the
      transcription starting sites (TSSs). The 5'-regulatory axis of B4GALT1 also
      included five more novel TFBSs for CTCF, GLI1, TCF7L2, GATA3 and SOX5, in
      addition to unique (TG)18 repeats in conjunction with 22 nucleotide TG-associated
      sequence (TGAS). The five lncRNA B4GALT1-AS1 transcripts showed significant
      complementarity with B4GALT1 mRNA. In contrast, the rest of B4GALT genes showed
      fewer lncRNAs, and all lacked the (TG)18 and TGAS. Our results are strongly
      supported by the FANTOM5 study which showed tissue-specific variations in
      transcript origination sites for this gene. We suggest that the unique expression
      patterns for the B4GALT1 in normal and malignant tissues are controlled by a
      differential usage of 5'-B4GALT1 regulatory units along with a post
      transcriptional regulation by the antisense RNA, which in turn govern the cell
      matrix interactions, neoplastic progression, anticancer drug sensitivity, and
      could be utilized in personalized therapy.

PMID- 26315937
TI  - Sugar-dependent modulation of neuronal development, regeneration, and plasticity
      by chondroitin sulfate proteoglycans.
AB  - Chondroitin sulfate proteoglycans (CSPGs) play important roles in the developing
      and mature nervous system, where they guide axons, maintain stable connections,
      restrict synaptic plasticity, and prevent axon regeneration following CNS injury.
      The chondroitin sulfate glycosaminoglycan (CS GAG) chains that decorate CSPGs are
      essential for their functions. Through these sugar chains, CSPGs are able to bind
      and regulate the activity of a diverse range of proteins. CSPGs have been found
      both to promote and inhibit neuronal growth. They can promote neurite outgrowth
      by binding to various growth factors such as midkine (MK), pleiotrophin (PTN),
      brain-derived neurotrophic factor (BDNF) and other neurotrophin family members.
      CSPGs can also inhibit neuronal growth and limit plasticity by interacting with
      transmembrane receptors such as protein tyrosine phosphatase sigma (PTPsigma),
      leukocyte common antigen-related (LAR) receptor protein tyrosine phosphatase, and
      the Nogo receptors 1 and 3 (NgR1 and NgR3). These CS-protein interactions depend
      on specific sulfation patterns within the CS GAG chains, and accordingly,
      particular CS sulfation motifs are upregulated during development, in the mature
      nervous system, and in response to CNS injury. Thus, spatiotemporal regulation of
      CS GAG biosynthesis may provide an important mechanism to control the functions
      of CSPGs and to modulate intracellular signaling pathways. Here, we will discuss
      these sulfation-dependent processes and highlight how the CS sugars on CSPGs
      contribute to neuronal growth, axon guidance, and plasticity in the nervous
      system. 

PMID- 26315940
TI  - How does tobacco smoke influence the morphometry of the fetus and the umbilical
      cord?-Research on pregnant women with intrauterine growth restriction exposed to
      tobacco smoke.
AB  - Proper structure of the umbilical cord is important for the fetal development. We
      evaluated effects of toxic factors from tobacco smoke on fetal and umbilical cord
      morphometry. 109 women in weeks 29-40 of pregnancy (31 smokers with intrauterine
      growth restriction (IUGR); 28 non-smoking women with IUGR; 50 healthy
      pregnancies) were included. In smokers with IUGR, cotinine, cadmium and lead
      concentrations were significantly higher than in controls (mean 55.23ng/l;
      1.52ng/ml; 14.85ng/ml vs 1.07; 0.34; 9.42) and inverse correlation between lead
      concentration and uncoiled umbilical cord was significant (r=-0.80). In smokers
      with IUGR, area of Wharton's jelly was increased compared to nonsmokers and
      controls. Inverse correlations occurred between cotinine and cadmium
      concentration and fetal percentile in smokers (r=-0.87; r=-0.87) and non-smokers
      (r=-0.47; r=-0.78) with IUGR. Exposure to tobacco smoke measured by cotinine,
      cadmium and lead concentration has an impact on fetal growth and umbilical cord
      morphometry and correlates with intensity of IUGR. 

PMID- 26315941
TI  - Metal-free and Scalable Synthesis of Porous Hyper-cross-linked Polymers: Towards
      Applications in Liquid-Phase Adsorption.
AB  - A metal-free route for the synthesis of hyper-cross-linked polymers (HCP) based
      on Bronsted acids such as trifluoromethanesulfonic acid as well as H2 SO4 is
      reported. It is an improved method compared to conventional synthesis strategies
      that use stoichiometric amounts of metal-based Lewis acids such as FeCl3 . The
      resulting high-performance adsorbents exhibit a permanent porosity with high
      specific surface areas up to 1842 m(2)  g(-1) . Easy scalability of the HCP
      synthesis is proven on the multi-gram scale. All chemo-physical properties are
      preserved. Water-vapor adsorption shows that the resulting materials exhibit an
      even more pronounced hydrophobicity compared to the conventionally prepared
      materials. The reduced surface polarity enhances the selectivity in the liquid
      phase adsorption of the biogenic platform chemical 5-hydroxymethylfurfural. 

PMID- 26315942
TI  - Functional impairment and mental health functioning among Vietnamese children.
AB  - PURPOSE: Functional impairment is a key indicator of need for mental health
      services among children and adolescents, often a stronger predictor of service
      usage than mental health symptoms themselves. Functional impairment may be of
      particular importance in low- and middle-income countries (LMIC) because of its
      potential to focus policy on treatment of child mental health problems which is
      generally given low priority in LMIC. However, few studies have assessed
      functional impairment in LMIC. The present study assessed rates of functional
      impairment among children in Vietnam, as a case example of an LMIC, as well as
      effects of other risk/protective factors of particular relevance to LMIC (e.g.,
      whether the family lived in an urban or rural area; family structure variables
      such as grandparents living with the family). METHODS: 1314 parents of children 6
      16 years old from 10 Vietnamese provinces were interviewed. RESULTS: The overall
      rate of functional impairment among Vietnamese children was 20 %, similar to
      rates in high-income countries such as Germany and the United States, suggesting
      that LMIC status may not be associated with dramatic increases in functional
      impairment in children. Functional impairment was significantly greater among
      mental health cases than non-cases, with increases of over 550 % associated with
      mental health caseness. A number of other risk factors (e.g., marital status) had
      smaller but significant effects. CONCLUSIONS: Mental health problems are a major
      but not the sole contributor to functional impairment among Vietnamese children.
      The pragmatic significance of this research lies in its potential to affect
      public awareness and policy related to child mental health in LMIC.

PMID- 26315943
TI  - Isolated facial diplegia in Guillain-Barre syndrome: Bifacial weakness with
      paresthesias.
AB  - Bifacial weakness with paresthesias (BFP) is a subtype of Guillain-Barre syndrome
      defined by rapidly progressive bilateral facial weakness in the absence of other
      cranial neuropathies, ataxia, or limb weakness. Many patients also complain of
      distal limb paresthesias and display diminished or absent deep tendon reflexes.
      BFP is a localized form of Guillain-Barre syndrome and is thought to be caused
      exclusively by demyelinating- rather than axonal-type neuropathy. Patients with
      BFP do not display anti-ganglioside IgG antibodies. Since it is rare, many
      physicians are unfamiliar with BFP, as bilateral facial weakness is more commonly
      associated with sarcoidosis, Lyme disease, or meningeal pathology. Many patients
      diagnosed with bilateral Bell palsy may instead have BFP. In this review, we
      highlight the clinical features of BFP and outline diagnostic criteria.

PMID- 26315944
TI  - Nicotinic acetylcholine receptors mediate donepezil-induced oligodendrocyte
      differentiation.
AB  - Oligodendrocytes are the myelin-forming cells of the central nervous system
      (CNS). Failure of myelin development and oligodendrocyte loss results in serious
      human disorders, including multiple sclerosis. Here, we show that donepezil, an
      acetlycholinesterase inhibitor developed for the treatment of Alzheimer's
      disease, can stimulate oligodendrocyte differentiation and maturation of neural
      stem cell-derived oligodendrocyte progenitor cells without affecting
      proliferation or cell viability. Transcripts for essential myelin-associated
      genes, such as PLP, MAG, MBP, CNPase, and MOG, in addition to transcription
      factors that regulate oligodendrocyte differentiation and myelination, were
      rapidly increased after treatment with donepezil. Furthermore, luciferase assays
      confirmed that both MAG and MBP promoters display increased activity upon
      donepezil-induced oligodendrocytes differentiation, suggesting that donepezil
      increases myelin gene expression mainly through enhanced transcription. We also
      found that the increase in the number of oligodendrocytes observed following
      donepezil treatment was significantly inhibited by the nicotinic acetylcholine
      receptor (nAChR) antagonist mecamylamine, but not by the muscarinic acetylcholine
      receptor antagonist scopolamine. Moreover, donepezil-induced myelin-related gene
      expression was suppressed by mecamylamine at both the mRNA and protein level.
      These results suggest that donepezil stimulates oligodendrocyte differentiation
      and myelin-related gene expression via nAChRs in neural stem cell-derived
      oligodendrocyte progenitor cells. We show that donepezil, a drug for the
      treatment of Alzheimer disease, can stimulate oligodendrocyte differentiation and
      maturation of oligodendrocyte progenitor cells. Transcripts for essential myelin
      associated genes, such as PLP, MAG, MBP, CNPase and MOG in addition to
      transcripton factors that regulate oligodendrocyte differentiation and
      myelination were rapidly increased after treatment with donepezil. These effects
      were partly dependent on nicotinic acetylcholine receptor (nAChR). 

PMID- 26315945
TI  - Lysozyme adsorption at a silica surface using simulation and experiment: effects
      of pH on protein layer structure.
AB  - Hen Egg White Lysozyme (HEWL) is a widely used exemplar to study protein
      adsorption on surfaces and interfaces. Here we use fully atomistic Molecular
      Dynamics (MD) simulations, Multi-Parametric Surface Plasmon Resonance (MP-SPR),
      contact angle and zeta potential measurements to study HEWL adsorption at a
      silica surface. The simulations provide a detailed description of the adsorption
      mechanism and indicate that at pH7 the main adsorption driving force is
      electrostatics, supplemented by weaker hydrophobic forces. Moreover, they reveal
      the preferred orientation of the adsorbed protein and show that its structure is
      only slightly altered at the interface with the surface. This provides the basis
      for interpreting the experimental results, which indicate the surface adsorbs a
      close-packed monolayer at about pH10 where the surface has a large negative zeta
      potential and the HEWL is positively charged. At higher pH, the adsorption amount
      of the protein layer is greatly reduced due to the loss of charge on the protein.
      At lower pH, the smaller zeta potential of the surface leads to lower HEWL
      adsorption. These interpretations are complemented by the contact angle
      measurements that show how the hydrophobicity of the surface is greatest when the
      surface coverage is highest. The simulations provide details of the hydrophobic
      residues exposed to solution by the adsorbed HEWL, completing the picture of the
      protein layer structure. 

PMID- 26315946
TI  - Degradation of polypropylene in vivo: A microscopic analysis of meshes explanted
      from patients.
AB  - Polypropylene meshes, originally introduced for hernia repair, are presently
      utilized in several anatomical sites. Several million are implanted annually
      worldwide. Depending on the device, up to 10% will be excised to treat
      complications. The excised meshes can provide material to study the
      complications, however, they have remained underutilized over the last decades
      and the mechanisms of complications continue to be incompletely understood. The
      fundamental question as to whether polypropylene degrades in vivo is still
      debated. We have examined 164 excised meshes using conventional microscopy to
      search for features of polypropylene degradation. Four specimens were also
      examined by transmission electron microscopy. The degraded material, detected by
      its ability to absorb dyes in the degradation nanopores, formed a continuous
      layer at the surface of the mesh fibers. It retained birefringence, inclusions of
      non-degraded polypropylene, and showed ability to meld with the non-degraded
      fiber core when heated by the surgical cautery. Several features indicated that
      the degradation layer formed in vivo: inflammatory cells trapped within fissures,
      melting caused by cautery of excision surgery, and gradual but progressive growth
      of the degradation layer while in the body. Cracking of the degraded material
      indicated a contribution to clinically important mesh stiffening and deformation.
      Chemical products of degradation need to be analyzed and studied for their role
      in the mesh-body interactions. The described methods can also be used to study
      degradation of other materials. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater
      Res Part B: Appl Biomater, 105B: 237-248, 2017.

PMID- 26315947
TI  - False-positive finding of retropharyngeal lymph node recurrence in both fluorine
      (18)FDG PET and MRI in a patient with nasopharyngeal carcinoma.
AB  - BACKGROUND: Biopsy of the retropharyngeal node is not routinely accessible. The
      diagnosis of retropharyngeal lymph node recurrence in patients with
      nasopharyngeal carcinoma (NPC) is often based on an imaging study. METHODS: We
      reported a patient with NPC who was incorrectly diagnosed with left
      retropharyngeal lymph node recurrence by both MRI and positron emission
      tomography (PET)/CT. RESULTS: A woman who was treated for stage IVA NPC 2 years
      previously was found to have a nodal lesion in the left retropharyngeal space on
      MRI together with focal fluorodeoxyglucose (FDG) uptake on PET/CT. Locoregional
      recurrence was suspected, and surgery was performed. Subsequent pathology results
      showed reactive lymphoid hyperplasia. CONCLUSION: Although tissue biopsy for the
      retropharyngeal node is technically difficult, this case demonstrates that tumor
      recurrence cannot be diagnosed even based on both positive findings on MRI and
      PET/CT in patients with NPC.

PMID- 26315948
TI  - Pharmacological Management of Opioid Use Disorder in Pregnant Women.
AB  - Opioid misuse during pregnancy is associated with negative outcomes for both
      mother and fetus due not only to the physiological effects of the drug but also
      to the associated social, medical and mental health problems that accompany
      illicit drug use. An interdisciplinary approach to the treatment of opioid use
      disorder during pregnancy is most effective. Ideally, obstetric and substance use
      treatment are co-located and ancillary support services are readily available.
      Medication-assisted treatment with methadone or buprenorphine is intrinsic to
      evidence-based care for the opioid-using pregnant woman. Women who are not
      stabilized on an opioid maintenance medication experience high rates of relapse
      and worse outcomes. Methadone has been the mainstay of maintenance treatment for
      nearly 50 years, but recent research has found that both methadone and
      buprenorphine maintenance treatments significantly improve maternal, fetal and
      neonatal outcomes. Although methadone remains the current standard of care, the
      field is beginning to move towards buprenorphine maintenance as a first-line
      treatment for pregnant women with opioid use disorder, because of its greater
      availability and evidence of better neonatal outcomes than methadone. However,
      there is some evidence that treatment dropout may be greater with buprenorphine
      relative to methadone.

PMID- 26315950
TI  - Radiographic axial spondyloarthritis versus ankylosing spondylitis.

PMID- 26315951
TI  - Identification of complications that have a significant effect on length of stay
      after spine surgery and predictive value of 90-day readmission rate.
AB  - OBJECT: Complications after spine surgery have an impact on overall outcome and
      health care expenditures. The increased cost of complications is due in part to
      associated prolonged hospital stays. The authors propose that certain
      complications have a greater impact on length of stay (LOS) than others and that
      those complications should be the focus of future targeted prevention efforts.
      They conducted a retrospective analysis of a prospectively maintained database to
      identify complications with the greatest impact on LOS as well as the predictive
      value of these complications with respect to 90-day readmission rates. METHODS:
      Data on 249 patients undergoing spine surgery at Thomas Jefferson University from
      May to December 2008 were collected by a study auditor. Any complications
      occurring within 30 days of surgery were recorded as was overall LOS for each
      patient. Stepwise regression analysis was performed to determine whether specific
      complications had a statistically significant effect on LOS. For correlation, all
      readmissions within 90 days were recorded and organized by complication for
      comparison with those complications affecting LOS. RESULTS: The mean LOS for
      patients without postoperative complications was 6.9 days. Patients who developed
      pulmonary complications had an associated increase in LOS of 11.1 days (p <
      0.005). The development of a urinary tract infection (UTI) was associated with an
      increase in LOS of 3.4 days (p = 0.002). A new neurological deficit was
      associated with an increase in LOS of 8.2 days (p = 0.004). Complications
      requiring return to the operating room (OR) showed a trend toward an increase in
      LOS of 4.7 days (p = 0.09), as did deep wound infections (3.3 days, p = 0.08).
      The most common reason for readmission was for wound drainage (n = 21; surgical
      drainage was required in 10 [4.01%] of these 21 cases). The most common diagnoses
      for readmission, in decreasing order of incidence, were categorized as hardware
      malpositioning (n = 4), fever (n = 4), pulmonary (n = 2), UTI (n = 2), and
      neurological deficit (n = 1). Complications affecting LOS were not found to be
      predictive of readmission (p = 0.029). CONCLUSIONS: Postoperative complications
      in patients who have undergone spine surgery are not uncommon and are associated
      with prolonged hospital stays. In the current cohort, the occurrence of pulmonary
      complications, UTI, and new neurological deficit had the greatest effect on
      overall LOS. Further study is required to determine the causative factors
      affecting readmission. These specific complications may be high-yield targets for
      cost reduction and/or prevention efforts.

PMID- 26315949
TI  - The RESPECT study: RESearch on the PrEvalence and the diagnosis of COPD and its
      Tobacco-related etiology: a study protocol.
AB  - BACKGROUND: Smoking remains a leading health risk factor among Europeans.
      Tobacco, together with other factors, will lead to an expansive epidemic of
      chronic diseases, including COPD, among the working population in Russia. The
      general aim of the RESearch on the PrEvalence and the diagnosis of COPD and its
      Tobacco-related etiology (RESPECT) study is to gain a better understanding of the
      prevalence, pathogenesis and symptoms of COPD. METHODS/DESIGN: The RESPECT study
      is a prospective, population-based cohort study of subjects aged 35-70 years in
      two north-west regions of the Russian Federation (Saint Petersburg and
      Arkhangelsk). The study includes three components: a cross-sectional study
      (prevalence), a case-control study and a cohort study (diagnostic). An
      investigator who interviewed the patient completed three questionnaires.
      Spirometry, including a reversibility test, was offered to all participants.
      Individuals displaying forced expiratory volume in 1 s (FEV1)/forced vital
      capacity (FVC) < 0.7 and/or FEV1/FVC < the lower limit of normal before and/or
      after bronchodilation were included in a follow-up study and were examined by a
      pulmonologist using a standardized comprehensive examination protocol. A future
      case-control study of two matched groups of patients (heavy smokers with COPD
      versus heavy smokers without COPD) will provide information on which factors
      (biomarkers, including pneumoproteins, in serum and induced sputum) are related
      to tobacco-induced COPD. DISCUSSION: In total, 3133 individuals (2122 from St.
      Petersburg and 1012 from Arkhangelsk) aged 35-70 years agreed to participate in
      this study and met the inclusion criteria. In total, 2974 participants met the
      quality criteria for spirometry, and 2388 reversibility tests were performed. A
      cohort of newly defined obstructive pulmonary disease patients (247 persons) was
      established for follow-up investigation. The RESPECT study will provide
      information regarding the prevalence of COPD in the north-west region of the
      Russian Federation. Moreover, the comprehensive RESPECT database will enable us
      to explore new research questions, provide novel insight into the risk factors
      and different phenotypes of COPD, and contribute to an improved understanding of
      the reasons why some heavy smokers develop the disease whereas others do not.
      CLINICAL TRIAL REGISTRATION: NCT02307799 (the release date: 12/01/2014).

PMID- 26315952
TI  - Concurrent spinal schwannoma and meningioma mimicking a single cervical dumbbell
      shaped tumor: case report.
AB  - Dumbbell-shaped tumors consisting of 2 different tumors are extremely rare.
      Herein, the authors present a case of concurrent spinal schwannoma and meningioma
      mimicking a single cervical dumbbell-shaped tumor. A 64-year-old man presented
      with a 5-year history of gradually exacerbating left occipital pain without
      clinical evidence of neurofibromatosis. Magnetic resonance imaging showed an
      extradural tumor along the left C-2 nerve root with a small intradural component.
      The tumor was approached via a C-1 hemilaminectomy. The intradural tumor was
      resected together with the extradural tumor after opening the dura mater. The
      intradural tumor was attached to the dura mater around the exit point of the C-2
      nerve root. Intraoperative biopsy revealed that the extradural tumor was a
      schwannoma and that the intradural tumor was a meningioma. The dura mater
      adjacent to the tumor was then coagulated and resected. Postoperative
      pathological examination confirmed the same diagnoses with no evidence of
      continuity between the intra- and extradural components. The patient's
      postoperative clinical course was uneventful. Clinicians should be aware that
      cervical dumbbell-shaped tumors can consist of 2 different tumors. 

PMID- 26315954
TI  - Sacroiliac joint fusion.

PMID- 26315953
TI  - Impact of dynamic alignment, motion, and center of rotation on myelopathy grade
      and regional disability in cervical spondylotic myelopathy.
AB  - OBJECT: Cervical stenosis is a defining feature of cervical spondylotic
      myelopathy (CSM). Matsunaga et al. proposed that elements of stenosis are both
      static and dynamic, where the dynamic elements magnify the canal deformation of
      the static state. For the current study, the authors hypothesized that dynamic
      changes may be associated with myelopathy severity and neck disability. This goal
      of this study was to present novel methods of dynamic motion analysis in CSM.
      METHODS: A post hoc analysis was performed of a prospective, multicenter database
      of patients with CSM from the AOSpine North American study. One hundred ten
      patients (34%) met inclusion criteria, which were symptomatic CSM, age over 18
      years, baseline flexion/extension radiographs, and health-related quality of life
      (HRQOL) questionnaires (modified Japanese Orthopaedic Association [mJOA] score,
      Neck Disability Index [NDI], the 36-Item Short Form Health Survey Physical
      Component Score [SF-36 PCS], and Nurick grade). The mean age was 56.9 +/- 12
      years, and 42% of patients were women (n = 46). Correlations with HRQOL measures
      were analyzed for regional (cervical lordosis and cervical sagittal vertical
      axis) and focal parameters (kyphosis and spondylolisthesis between adjacent
      vertebrae) in flexion and extension. Baseline dynamic parameters
      (flexion/extension cone relative to a fixed C-7, center of rotation [COR], and
      range of motion arc relative to the COR) were also analyzed for correlations with
      HRQOL measures. RESULTS: At baseline, the mean HRQOL measures demonstrated
      disability and the mean radiographic parameters demonstrated sagittal
      malalignment. Among regional parameters, there was a significant correlation
      between decreased neck flexion (increased C2-7 angle in flexion) and worse Nurick
      grade (R = 0.189, p = 0.048), with no significant correlations in extension.
      Focal parameters, including increased C-7 sagittal translation overT-1 (slip),
      were significantly correlated with greater myelopathy severity (mJOA score,
      Flexion R = -0.377, p = 0.003; mJOA score, Extension R = -0.261, p = 0.027).
      Sagittal slip at C-2 and C-4 also correlated with worse HRQOL measures. Reduced
      flexion/extension motion cones, a more posterior COR, and smaller range of motion
      correlated with worse general health SF-36 PCS and Nurick grade. CONCLUSIONS:
      Dynamic motion analysis may play an important role in understanding CSM. Focal
      parameters demonstrated a significant correlation with worse HRQOL measures,
      especially increased C-7 sagittal slip in flexion and extension. Novel methods of
      motion analysis demonstrating reduced motion cones correlated with worse
      myelopathy grades. More posterior COR and smaller range of motion were both
      correlated with worse general health scores (SF-36 PCS and Nurick grade). To our
      knowledge, this is the first study to demonstrate correlation of dynamic motion
      and listhesis with disability and myelopathy in CSM.

PMID- 26315955
TI  - Cost minimization in treatment of adult degenerative scoliosis.
AB  - OBJECT: Back pain is an increasing concern for the aging population. This study
      aims to evaluate if minimally invasive surgery presents cost-minimization
      benefits compared with open surgery in treating adult degenerative scoliosis.
      METHODS: Seventy-one patients with adult degenerative scoliosis received 2-stage,
      multilevel surgical correction through either a minimally invasive spine surgery
      (MIS) approach with posterior instrumentation (n = 38) or an open midline (Open)
      approach (n = 33). Costs were derived from hospital and rehabilitation charges.
      Length of stay, blood loss, and radiographic outcomes were obtained from
      electronic medical records. Functional outcomes were measured with Oswestry
      Disability Index (ODI) and visual analog scale (VAS) surveys. RESULTS: Patients
      in both cohorts were similar in age (Age(MIS) = 65.68 yrs, Age(Open) = 63.58 yrs,
      p = 0.28). The mean follow-up was 18.16 months and 21.82 months for the MIS and
      Open cohorts, respectively (p = 0.34). MIS and Open cohorts had an average of
      4.37 and 7.61 levels of fusion, respectively (p < 0.01). Total inpatient charges
      were lower for the MIS cohort ($269,807 vs $391,889, p < 0.01), and outpatient
      rehabilitation charges were similar ($41,072 vs $49,272, p = 0.48). MIS patients
      experienced reduced length of hospital stay (7.03 days vs 14.88 days, p < 0.01)
      and estimated blood loss (EBL) (EBL(MIS) = 470.26 ml, EBL(Open)= 2872.73 ml, p <
      0.01). Baseline ODI scores were lower in the MIS cohort (40.03 vs 48.04, p =
      0.03), and the cohorts experienced similar 1-year improvement (DeltaODI(MIS) = 
      15.98, DeltaODI(Open) = -21.96, p = 0.25). Baseline VAS scores were similar
      (VAS(MIS) = 6.56, VAS(Open)= 7.10, p = 0.32), but MIS patients experienced less
      reduction after 1 year (DeltaVAS(MIS) = -3.36, DeltaVAS(Open) = -4.73, p = 0.04).
      Preoperative sagittal vertical axis (SVA) were comparable (preoperative SVA(MIS)
      = 63.47 mm, preoperative SVA(Open) = 71.3 mm, p = 0.60), but MIS patients had
      larger postoperative SVA (postoperative SVA(MIS) = 51.17 mm, postoperative
      SVA(Open) = 28.17 mm, p = 0.03). CONCLUSIONS: Minimally invasive surgery
      demonstrated reduced costs, blood loss, and hospital stays, whereas open surgery
      exhibited greater improvement in VAS scores, deformity correction, and sagittal
      balance. Additional studies with more patients and longer follow-up will
      determine if MIS provides cost-minimization opportunities for treatment of adult
      degenerative scoliosis.

PMID- 26315956
TI  - Selective versus nonselective thoracic fusion in Lenke 1C curves: a meta-analysis
      of baseline characteristics and postoperative outcomes.
AB  - OBJECT: Lenke 1C curves are challenging to manage surgically due to the
      structural thoracic deformity and nonstructural lumbar curve. Selective thoracic
      fusion (STF) is considered the standard of care because it preserves motion of
      the lumbar segment, yet nonselective STF (NSTF) remains prevalent. This study
      aims to identify baseline patient characteristics that drive treatment and to
      compare postoperative outcomes for both procedures. METHODS: Studies that
      compared baseline and postoperative demographic data, health-related quality of
      life (HRQL) questionnaires, and radiographic parameters of patients with Lenke 1C
      curves undergoing STF or NSTF were identified for meta-analysis. The effect
      measure is expressed as a mean difference (MD) with 95% CI. A positive MD
      signifies a greater STF value, or a mean increase within the group. RESULTS: One
      prospective and 6 retrospective case-control studies with sample size of 488
      patients (344 STF and 144 NSTF) were identified. Baseline age, sex, and HRQLs
      were equivalent, except for better scores in the STF group for the Scoliosis
      Appearance Questionnaire (SAQ): Unrelated to Deformity item (3.47 vs 3.88, p =
      0.01) and the Spine Research Society questionnaire, Item 22: Pain (4.13 vs 3.92,
      p = 0.04). Radiographic findings were significantly worse in NSTF, as measured by
      the thoracolumbar/lumbar (TL/L) Cobb angle (MD: -4.29 degrees , p < 0.01) and
      TL/L apical vertebral translation (AVT) (MD: -6.08, p < 0.01). Radiographic
      findings significantly improved in STF, as measured in the main thoracic (MT)
      Cobb angle (MD: -27.78 degrees , p < 0.01), TL/L Cobb angle (MD: -16.24 degrees ,
      p < 0.01), MT:TL/L Cobb ratio (MD: -0.21, p < 0.01), coronal balance (MD: 0.47, p
      = 0.02), and thoracic kyphosis (MD: 7.87 degrees , p < 0.01); and in NSTF in
      proximal thoracic (PT) Cobb angle (24 degrees  vs 14.1 degrees , p < 0.01), MT
      Cobb angle (53.5 degrees  vs 20.5 degrees , p < 0.01), and TL/L Cobb angle (41.6
      degrees  vs 16.6 degrees , p < 0.01). Postoperative TL/L Cobb angle (23.1 degrees
      vs 16.6 degrees , p < 0.01) was significantly higher in STF; but PT Cobb angle,
      MT Cobb angle, and MT:TL/L Cobb ratio are equivalent. CONCLUSIONS: Patients with
      larger lumbar compensatory curves displaying a larger degree of coronal
      translation, as measured by the TL/L AVT, are more likely to undergo an NSTF.
      Contrary to established guidelines, larger MT curve magnitudes and MT:TL/L Cobb
      angle ratios have not been found to influence the decision to pursue a selective
      thoracic fusion. Although overall both STF and NSTF groups are found to have
      effective postoperative coronal balance, the STF group has only modest
      improvements in the lumbar curve position as determined by a relatively unchanged
      TL/L AVT. Furthermore, surgeons may prefer NSTF in patients who may have a worse
      overall perception of their spinal deformity as measured by HRQL measures of pain
      and desire for appearance change.

PMID- 26315957
TI  - Utility of nonpenetrating titanium clips for dural closure during spinal surgery
      to prevent postoperative cerebrospinal fluid leakage.
AB  - OBJECT: The nonpenetrating titanium clip has been successfully used in peripheral
      arterial bypass surgery. The purpose of this study was to evaluate the leakage
      pressures and patterns of nonpenetrating titanium clips using a simple model that
      mimicked spinal surgery. In addition, the authors describe their surgical
      experience with these clips and the follow-up results in 31 consecutive patients.
      METHODS: The authors compared nonpenetrating titanium clips and expanded
      polytetrafluoroethylene (ePTFE) sutures in relation to the water pressure that
      could be tolerated by sutured ePTFE sheets, and the leakage pressure patterns
      were determined. The changes in leakage pressures at 5 minutes, 30 minutes, and
      12 hours were examined when the clips and sutures were used in combination with
      the mesh-and-glue technique in an in vitro study. Thirty-one patients underwent
      spinal intradural procedures using nonpenetrating titanium clips to suture the
      dura maters using the meshand-glue technique, involving fibrin glue and
      polyglycolic acid-fibrin sheets. RESULTS: A significant difference was apparent
      between the ePTFE suture group and the nonpenetrating titanium clip group, with
      the latter showing a leakage pressure that could be sustained and was 1508%
      higher than that of the former (p = 0.001). In relation to leakage patterns, the
      nonpenetrating titanium clips did not make any suture holes in the ePTFE sheet
      and fluid leakage occurred between the clips, whereas fluid leakage was
      associated with the pressure elevation that occurred at the suture holes made by
      the ePTFE sutures. Of the 31 patients who underwent spinal intradural procedures
      using nonpenetrating titanium clips, 1 (3.2%) experienced cerebrospinal fluid
      (CSF) leakage postoperatively. No other complications-for example, allergic
      reactions, adhesions, or infections--were encountered. CONCLUSIONS: The
      interrupted placement of nonpenetrating titanium clips enables dural closure
      without creating any holes. These clips facilitate improvements in the initial
      leakage pressure and reduce postoperative CSF leakage following spinal surgery.
      The authors conclude that it is very beneficial to suture the spinal dura mater
      using nonpenetrating titanium clips given the anatomical characteristics of the
      spinal dura mater and the fact that the clips do not create suture holes.

PMID- 26315958
TI  - Odontoid process inclination in normal adults and in an adult population with
      Chiari malformation Type I.
AB  - OBJECT: Posterior odontoid process inclination has been demonstrated as a factor
      associated with Chiari malformation Type I (CM-I) in the pediatric population;
      however, no studies to date have examined this measurement in the adult CM-I
      population. The purpose of this study was to evaluate craniocervical junction
      (CCJ) measurements in adult CM-I versus a control group. METHODS: The odontoid
      retroflexion, odontoid retroversion, odontoid height, posterior basion to C-2
      line measured to the dural margin (pB-C2 line), posterior basion to C-2 line
      measured to the dorsal odontoid cortical margin (pB-C2* line), and clivus-canal
      angle measurements were retrospectively analyzed in adult patients with CM-I
      using MRI. These measurements were compared with normative values established
      from CT scans of the cervical spine in adults without CM-I. RESULTS: A
      statistically significant difference was found between 55 adults with CM-I and
      150 sex-matched controls (125 used for analysis) in the mean clivus-canal angle
      and the mean pB-C2 line. CONCLUSIONS: These data suggest that there are sex
      specific differences with respect to measurements at the CCJ between men and
      women, with women showing a more posteriorly inclined odontoid process. There
      were also differences between the CM-I and control groups: a more acute clivus
      canal angle was associated with CM-I in the adult population. These CCJ findings
      could have an influence on presurgical planning.

PMID- 26315959
TI  - Minimally invasive anterior lumbar interbody fusion for adult degenerative
      scoliosis with 1 or 2 dislocated levels.
AB  - OBJECT: Frequent complications of posterolateral instrumented fusion have been
      reported after treatment of degenerative scoliosis in elderly patients.
      Considering that in some cases, most of the symptomatology of adult degenerative
      scoliosis (ADS) is a consequence of the segmental instability at the dislocated
      level, the use of minimally invasive anterior lumbar interbody fusion (ALIF) to
      manage symptoms can be advocated to reduce surgical morbidity. The purpose of
      this study was to evaluate the midterm outcomes of 1- or 2-level minimally
      invasive ALIFs in ADS patients with 1- or 2-level dislocations. METHODS: A total
      of 47 patients (average age 64 years; range 43-80 years) with 1- or 2-level ALIF
      performed for ADS (64 levels) in a single institution were included in the study.
      An independent spine surgeon retrospectively reviewed all the patients' medical
      records and radiographs to assess operative data and surgery-related
      complications. Clinical outcome was reported using the Oswestry Disability Index
      (ODI) and the visual analog scale (VAS) for lumbar and leg pain. Intraoperative
      data and complications were collected. Fusion and risk for adjacent-level
      degeneration were assessed. RESULTS: The mean follow-up duration was 3 years
      (range 1-10 years). ODI, and back and leg pain VAS scores were significantly
      improved at last follow-up. A majority of patients (74%) had a statistically
      significant improvement in their ODI score of more than 20 points at latest
      follow-up and 1 had a worsening of his disability. The mean operating time was
      166 minutes (range 70-355 minutes). The mean estimated blood loss was 410 ml
      (range 50-1700 ml). Six (5 major and 1 minor) surgical complications (12.7% of
      patients) and 13 (2 major and 11 minor) medical complications (27.7% of patients)
      occurred without death or wound infection. Fusion was achieved in 46 of 47
      patients. Surgery resulted in a slight but significant decrease of the Cobb
      angle, and improved the pelvic parameters and lumbar lordosis, but had no effect
      on the global sagittal balance. At latest follow-up, 9 patients (19.1%) developed
      adjacent-segment disease at a mean of 2 years' delay from the index surgery; 4
      were symptomatic but treated medically, and none required iterative surgery.
      CONCLUSIONS: Single- or 2-level minimally invasive fusion through a minimally
      invasive anterior approach in some selected cases of ADS produced a good
      functional outcome with a high fusion rate. They were associated with a
      significantly lower rate of complications in this study than the historical
      control.

PMID- 26315960
TI  - Nano-antioxidants: An emerging strategy for intervention against
      neurodegenerative conditions.
AB  - Oxidative stress has for long been linked to the neuronal cell death in many
      neurodegenerative conditions. Conventional antioxidant therapies have been less
      effective in preventing neuronal damage caused by oxidative stress due to their
      inability to cross the blood brain barrier. Nanoparticle antioxidants constitute
      a new wave of antioxidant therapies for prevention and treatment of diseases
      involving oxidative stress. It is believed that nanoparticle antioxidants have
      strong and persistent interactions with biomolecules and would be more effective
      against free radical induced damage. Nanoantioxidants include inorganic
      nanoparticles possessing intrinsic antioxidant properties, nanoparticles
      functionalized with antioxidants or antioxidant enzymes to function as an
      antioxidant delivery system. Nanoparticles containing antioxidants have shown
      promise as high-performance therapeutic nanomedicine in attenuating oxidative
      stress with potential applications in treating and preventing neurodegenerative
      conditions. However, to realize the full potential of nanoantioxidants, negative
      aspects associated with the use of nanoparticles need to be overcome to validate
      their long term applications. 

PMID- 26315961
TI  - Statistical survey of the buried waters in the Protein Data Bank.
AB  - The structures of buried water molecules were studied in an ensemble of high
      quality and non-redundant protein crystal structures. Buried water molecules were
      clustered and classified in lake-like clusters, which are completely isolated
      from the bulk solvent, and bay-like clusters, which are in contact with the bulk
      solvent through a surface water molecule. Buried water molecules are extremely
      common: lake-like clusters are found in 89 % of the protein crystal structures
      and bay-like clusters in 93 %. Clusters with only one water molecule are much
      more common than larger clusters. Both cluster types incline to be surrounded by
      loop residues, and to a minor extent by residues in extended secondary structure.
      Helical residues on the contrary do not tend to surround clusters of buried water
      molecules. One buried water molecule is found every 30-50 amino acid residues,
      depending on the secondary structures that are more abundant in the protein. Both
      main- and side-chain atoms are in contact with buried waters; they form four
      hydrogen bonds with the first water and 1-1.5 additional hydrogen bond for each
      additional water in the cluster. Consequently, buried water molecules appear to
      be firmly packed and rigid like the protein atoms. In this regard, it is
      remarkable to observe that prolines often surround water molecules buried in the
      protein interior. Interestingly, clusters of buried water molecules tend to be
      just beneath the protein surface. Moreover, water molecules tend to form a one
      dimensional wire rather than more compact arrangements. This agrees with recent
      evidence of the mechanisms of solvent exchange between internal cavities and bulk
      solvent.

PMID- 26315962
TI  - Radiologic damage at baseline predicts patient-related outcomes 18 years after
      the initiation of methotrexate therapy in patients with severe rheumatoid
      arthritis.
AB  - OBJECTIVES: We aimed to assess the association of the degree of radiologic damage
      at baseline with long-term patient-related outcomes (PRO) in patients with severe
      rheumatoid arthritis (RA). METHODS: This prospective observational single-centre
      study (Ratingen, Germany) included all RA patients starting treatment with
      methotrexate (MTX) between 1980 and 1987. Standardised clinical evaluations and
      radiographs of hands and feet were obtained at baseline and during the following
      years. About 18 years later, patients were invited for a re-assessment. PRO were
      assessed in three dimensions according to the International Classification of
      Functioning and Disability (ICF). Statistical analyses comprised multivariable
      models using baseline values for radiologic damage of hands and feet, age,
      gender, disease duration, rheumatoid factor positivity, measures of disease
      activity, and response to MTX as covariates. RESULTS: At baseline, the mean
      disease duration was 8.5 years. The disease was active with a mean number of
      swollen joints of 18 (out of 32) and a mean erythrocyte sedimentation rate of 55
      mm/hour. Radiologic damage was present in 95% of the patients. After 18 years,
      patient-related outcomes could be assessed in 78/271 patients (29%). Among chosen
      covariates, only the degree of baseline radiologic damage as measured by the
      Ratingen score was predictive of all long-term PRO (p<0.016). CONCLUSIONS: In
      this cohort including patients with severe RA, baseline radiologic damage was a
      good long-term predictor of PRO related to all three ICF dimensions.

PMID- 26315964
TI  - HPV vaccine acceptance in male adolescents.

PMID- 26315965
TI  - Does low level laser therapy relieve the pain caused by the placement of the
      orthodontic separators?--A meta-analysis.
AB  - OBJECTIVE: Pain caused by orthodontic treatment can affect patient's compliance
      and even force them to terminate treatments. The aim of this meta-analysis is to
      evaluate of the analgesic effect of low level laser therapy (LLLT) after
      placement of the orthodontic separators. METHODS: Five databases: PubMed, Embase,
      Cochrane library, China Biology Medicine disc (SinoMed CBM), China National
      Knowledge Infrastructure (CNKI) were searched for all the appropriate studies in
      June, 2014. Two reviewers screened the research results under our inclusion
      criteria and evaluated the risk of bias independently. Then the data of the
      included studies was extracted for quantitative analysis by the Review Manager
      5.1 software. RESULTS: Six studies were included in our meta-analysis finally.
      Comparing to the placebo group, the LLLT has good analgesic effect at 6 h, 1d,
      2d, 3d after placement of separators which is of statistical significance. While
      at 2 h, 4d, 5d after the placement, the results tend to support LLLT, but not
      statistically significant. CONCLUSION: Based on current included studies, LLLT
      can reduce the pain caused by the placement of separators effectively. However,
      because of the high heterogeneity, well designed RCTs are required in the future.

PMID- 26315966
TI  - Molecular and Histological Changes in Post-Treatment Biopsies of Non-Squamous Non
      Small Cell Lung Cancer: A Retrospective Study.
AB  - BACKGROUND: Recently, in advanced non-small cell lung cancer (NSCLC), standard
      chemotherapy was flanked by biological agents directed against genomic
      abnormalities, including EGFR and ALK alterations, that significantly improved
      patient outcome. Despite these achievements, tumour progression almost always
      occurs and a reassessment of the tumour genetic profile may contribute to
      modulating the therapeutic regimen. Resampling may provide tissue for additional
      tests to detect acquired resistance and/or new genetic alterations, but the
      currently available information is limited. PATIENTS AND METHODS: Histological
      and genetic reassessments of biopsy or surgical tissue samples from 50 non
      squamous NSCLC patients before and after at least one systemic treatment were
      performed. EGFR, KRAS, BRAF, PIK3CA and HER2 mutations were sequenced, p.T790M
      was identified with real-time PCR, and ALK and MET genomic alterations by
      fluorescence in situ hybridization. RESULTS: Overall in baseline biopsies, 37/50
      (74 %) tumours had genetic alterations, either single (52 %) or multiple (22 %).
      Among them, 16 were EGFR mutations and 6 ALK rearrangements. In the second tissue
      sampling, 54 % of cases had additional genomic changes, including newly acquired
      alterations (81 %) or losses (18 %). The commonest changes were MET amplification
      and p.T790M mutation. One case had a histological shift from adenocarcinoma to
      small cell carcinoma. CONCLUSIONS: The remarkable number of molecular changes
      following systemic therapy and the genetic complexity of some cases underline the
      value of histological and molecular re-evaluation of lung cancer to tailor the
      most appropriate therapy during disease progression.

PMID- 26315968
TI  - Competitive Gold-Promoted Meyer-Schuster and oxy-Cope Rearrangements of 3-Acyloxy
      1,5-enynes: Selective Catalysis for the Synthesis of (+)-(S)-gamma-Ionone and (-)
      (2S,6 R)-cis-gamma-Irone.
AB  - We report a simple, highly stereoselective synthesis of (+)-(S)-gamma-ionone and
      (-)-(2S,6R)-cis-gamma-irone, two characteristic and precious odorants; the latter
      compound is a constituent of the essential oil obtained from iris rhizomes. Of
      general interest in this approach are the photoisomerization of an endo
      trisubstituted cyclohexene double bond to an exo vinyl group and the installation
      of the enone side chain through a [(NHC)Au(I)]-catalyzed Meyer-Schuster-like
      rearrangement. This required a careful investigation of the mechanism of the gold
      catalyzed reaction and a judicious selection of reaction conditions. In fact, it
      was found that the Meyer-Schuster reaction may compete with the oxy-Cope
      rearrangement. Gold-based catalytic systems can promote either reaction
      selectively. In the present system, the mononuclear gold complex [Au(IPr)Cl], in
      combination with the silver salt AgSbF6 in 100:1 butan-2-one/H2O, proved to
      efficiently promote the Meyer-Schuster rearrangement of propargylic benzoates,
      whereas the digold catalyst [{Au(IPr)}2(MU-OH)][BF4] in anhydrous dichloromethane
      selectively promoted the oxy-Cope rearrangement of propargylic alcohols.

PMID- 26315967
TI  - Impact of Continuing First-Line EGFR Tyrosine Kinase Inhibitor Therapy Beyond
      RECIST Disease Progression in Patients with Advanced EGFR-Mutated Non-Small-Cell
      Lung Cancer (NSCLC): Retrospective GFPC 04-13 Study.
AB  - Retrospective studies suggested a benefit of first-line tyrosine kinase inhibitor
      (TKI) treatment continuation after response evaluation in solid tumors (RECIST)
      progression in epidermal growth factor receptor (EGFR)-mutated non-small-cell
      lung cancer (NSCLC) patients. The aim of this multicenter observational
      retrospective study was to assess the frequency of this practice and its impact
      on overall survival (OS). The analysis included advanced EGFR-mutated NSCLC
      patients treated with first-line TKI who experienced RECIST progression between
      June 2010 and July 2012. Among the 123 patients included (67 +/- 12.7 years,
      women: 69 %, non smokers: 68 %, PS 0-1: 87 %), 40.6 % continued TKI therapy after
      RECIST progression. There was no difference between the patients who did and did
      not continue TKI therapy with respect to progression-free survival (PFS1: 10.5
      versus 9.5 months, p = 0.4). Overall survival (OS) showed a non-significant trend
      in favor of continuing TKI therapy (33.0 vs. 21.2 months, p = 0.054).
      Progressions were significantly less symptomatic in the TKI continuation group
      than in the discontinuation group (18 % vs. 37 %, p < 0.01). Univariate analysis
      showed a higher risk of death among patients with PS >1 (HR 4.33, 95 %CI: 2.21
      8.47, p = 0.001), >1 one metastatic site (HR 1.96, 95 %CI: 1.06-3.61, p = 0.02),
      brain metastasis (HR 1.75, 95 %CI: 1.08-2.84, p = 0.02) at diagnosis, and a trend
      towards a higher risk of death in cases of TKI discontinuation after progression
      (HR 1.62, 95 %CI: 0.98-2.67, p = 0.056 ). In multivariate analysis only PS >1 (HR
      6.27, 95 %CI: 2.97-13.25, p = 0.00001) and >1 metastatic site (HR 2.54, 95 %CI:
      1.24-5.21, p = 0.02) at diagnosis remained significant. This study suggests that
      under certain circumstances, first-line TKI treatment continuation after RECIST
      progression is an acceptable option in EGFR-mutated NSCLC patients. CLINICAL
      TRIAL INFORMATION: NCT02293733.

PMID- 26315969
TI  - Salvage Procedures after Total Necrosis of a Free Jejunal Graft.
AB  - PURPOSE OF THE STUDY: To determine the appropriate salvage method after total
      necrosis of a jejunal graft after reconstruction of total
      laryngopharyngoesophagectomy or a larynx-preserving operation, considering the
      complexity of medical service in China. PROCEDURES: We reviewed 5 patients with a
      mean age of 61 years who developed total jejunal graft necrosis and underwent
      reconstruction of a free jejunal transfer in our hospital. The total number and
      choice of salvage procedures, the symptoms and the results of salvage for the 5
      patients have been reviewed. RESULTS: Four of the 5 patients survived. One of
      them underwent gastric pull-up reconstruction and recovered well. One patient
      died due to severe infection after the loss of the jejunal graft and secondary
      gastric pull-up reconstruction. A temporary external fistula was formed in 3
      patients after the initial jejunal graft necrosis, 2 of which underwent fistula
      repair 6 and 5 months later, while one went on long-term gastric tube feeding.
      CONCLUSION: Our results suggest that a temporary external fistula formation is an
      optional secondary salvage procedure after total necrosis of an initial jejunal
      graft, considering the relatively low quality of medical service in China.

PMID- 26315970
TI  - Evaluation of Fluorescence Imaging with Reflectance Enhancement (FIRE) for
      Quantifying Enamel Demineralization In vitro.
AB  - OBJECTIVES: To assess the ability of fluorescence imaging with reflectance
      enhancement (FIRE) to quantify early enamel demineralization in vitro. METHODS: A
      total of 30 bovine enamel specimens were immersed in demineralizing solution to
      produce artificial caries. Specimens were examined by FIRE, quantitative light
      induced fluorescence (QLF), and polarized light microscopy (PLM) at baseline and
      after 0.5, 1, 2, 4, 8, 24, 48 and 72 h of immersion. Fluorescence loss measured
      by FIRE and QLF was compared with lesion depth measurements by PLM. RESULTS: Over
      all time points, measurement of fluorescence loss by FIRE correlated well with
      the measurement of x0394;F by QLF and of x0394;Q by QLF. Both FIRE and QLF
      techniques showed significant correlation with PLM. CONCLUSION: FIRE technology
      may be useful for quantifying enamel demineralization in vitro.

PMID- 26315973
TI  - Circumferential cryoablation in a strictured esophagus: a feasibility and dose
      finding study in a porcine model after inducing stenosis by endoscopic mucosal
      resection.
AB  - In the treatment of early esophageal Barrett's neoplasia, radiofrequency ablation
      may be hindered by stenosis due to prior endoscopic resection (ER). The flexible
      balloon-based circumferential CryoBalloon Ablation System (CBAS) may overcome
      this problem by the conformability of the compliant balloon which might enable
      circumferential cryoablation in a stenosis. The aim of the current study was to
      evaluate the feasibility of the CBAS as well as the dose-response effect of
      cryoablation in a strictured esophagus model. In six pigs, a stenosis was induced
      by ER (3 cm in length, 75% of circumference) in the proximal, mid, and distal
      esophagus. After 28 days, cryoablation with the CBAS was performed, with the
      length of ablation time (6, 8, or 10 seconds) randomly assigned per stricture
      location within the esophagus. Four days post-ablation, the esophagi were
      harvested for histopathological assessment of the percentage of the total
      circumference affected by cryoablation and the maximum depth of necrosis. At 28
      days, all 18 ER areas had transformed into strictures with +/-50% of its original
      diameter remaining. In 9 of 18 strictures, more than one attempt for cryoablation
      was necessary due to displacement of the balloon. Histopathological evaluation
      showed a wide range in circumferential uniformity (0-100%) and maximum necrosis
      depth (epithelium to external proper muscle layer) of cryoablation, both
      independent of ablation times. Deepest ablation effects were seen at the center
      of the resection-induced scar. This first generation CryoBalloon Focal Ablation
      System was not feasible for ablation within severe stenoses, since it results in
      inconsistent circumferential uniformity of cryoablation with subsequent
      differences in depth of ablation. Further research with a next generation CBAS in
      a more realistic stricture model is warranted. 

PMID- 26315971
TI  - Deficient mismatch repair: Read all about it (Review).
AB  - Defects in the DNA mismatch repair (MMR) proteins, result in a phenotype called
      microsatellite instability (MSI), occurring in up to 15% of sporadic colorectal
      cancers. Approximately one quarter of colon cancers with deficient MMR (dMMR)
      develop as a result of an inherited predisposition syndrome, Lynch syndrome
      (formerly known as HNPCC). It is essential to identify patients who potentially
      have Lynch syndrome, as not only they, but also family members, may require
      screening and monitoring. Diagnostic criteria have been developed, based
      primarily on Western populations, and several methodologies are available to
      identify dMMR tumours, including immunohistochemistry and microsatellite testing.
      These criteria have provided evidence supporting the introduction of reflex
      testing. Yet, it is becoming increasingly clear that tests have a limited
      sensitivity and specificity and may yet be superseded by next generation
      sequencing. In this review, the limitations of diagnostic criteria are discussed,
      and current and emerging screening technologies explained. There is now useful
      evidence supporting the prognostic and predictive value of dMMR status in
      colorectal tumours, but much less is known about their value in extracolonic
      tumours, that may also feature in Lynch syndrome. This review assesses current
      literature relating to dMMR in endometrial, ovarian, gastric and melanoma
      cancers, which it would seem, may benefit from large-scale clinical trials in
      order to further close the gap in knowledge between colorectal and extracolonic
      tumours. 

PMID- 26315972
TI  - Temporal variation selects for diet-microbe co-metabolic traits in the gut of
      Gorilla spp.
AB  - Although the critical role that our gastrointestinal microbes play in host
      physiology is now well established, we know little about the factors that
      influenced the evolution of primate gut microbiomes. To further understand
      current gut microbiome configurations and diet-microbe co-metabolic fingerprints
      in primates, from an evolutionary perspective, we characterized fecal bacterial
      communities and metabolomic profiles in 228 fecal samples of lowland and mountain
      gorillas (G. g. gorilla and G. b. beringei, respectively), our closest
      evolutionary relatives after chimpanzees. Our results demonstrate that the gut
      microbiomes and metabolomes of these two species exhibit significantly different
      patterns. This is supported by increased abundance of metabolites and bacterial
      taxa associated with fiber metabolism in mountain gorillas, and enrichment of
      markers associated with simple sugar, lipid and sterol turnover in the lowland
      species. However, longitudinal sampling shows that both species' microbiomes and
      metabolomes converge when hosts face similar dietary constraints, associated with
      low fruit availability in their habitats. By showing differences and convergence
      of diet-microbe co-metabolic fingerprints in two geographically isolated primate
      species, under specific dietary stimuli, we suggest that dietary constraints
      triggered during their adaptive radiation were potential factors behind the
      species-specific microbiome patterns observed in primates today. 

PMID- 26315974
TI  - Novel, human cell line-derived recombinant factor VIII (human-cl rhFVIII;
      Nuwiq(r) ) in adults with severe haemophilia A: efficacy and safety.
AB  - INTRODUCTION: Nuwiq(r) [human cell line-derived recombinant factor VIII (human-cl
      rhFVIII)] is a new generation rFVIII protein, without chemical modification or
      fusion to any other protein, produced in a human cell line. AIM/METHODS: This
      prospective, open-label, multinational phase III study assessed the efficacy and
      safety of human-cl rhFVIII in 32 adult previously treated patients (PTPs) with
      severe haemophilia A during standard prophylaxis for >=6 months and >=50 exposure
      days. Efficacy in treating bleeds and during surgical prophylaxis was also
      assessed. RESULTS: Prophylactic efficacy, based on mean monthly bleeding rate,
      was rated as 'excellent' or 'good' in 97% of patients for all bleeds and in 100%
      of patients for spontaneous bleeds. Mean (SD) annualized bleeding rate was 2.28
      (3.73) [median = 0.9] for all bleeds, 1.16 (2.57) [median = 0] for spontaneous
      bleeds and 1.00 (1.79) [median = 0] for traumatic bleeds. There were no bleeds in
      50% of patients and there were no major, life-threatening bleeds. Efficacy was
      'excellent' or 'good' in treating 28 (100%) of 28 bleeds. Overall efficacy was
      rated as 'excellent' during four surgical procedures (three major, one minor) and
      'moderate' during one major surgery. Incremental in vivo recovery (IVR) data were
      comparable with the one-stage and chromogenic assays. IVR was >2.0% per IU kg-1
      for all measurements and stable over 6 months. No patients developed FVIII
      inhibitors and there were no treatment-related serious or severe adverse events.
      CONCLUSION: These results in adult PTPs indicate that human-cl rhFVIII is
      effective for the prevention and treatment of bleeds in adults with severe
      haemophilia A.

PMID- 26315975
TI  - Acoustophoretic removal of proteins from blood components.
AB  - This work presents the development of a miniaturized system for removing plasma
      proteins and other low-molecular-weight compounds from red blood cell (RBC)
      concentrate in a simple one-step-process using integrated ultrasound. The
      technology utilizes the principles of acoustophoresis to transfer the RBCs from
      the original plasma-containing solution into a protein-free SAG-M additive
      solution in a continuous flow process. The preparation of protein free RBC
      concentrate is important for blood transfusion to patients suffering from
      immunoglobulin A (IgA)-deficiency and developing antibodies against IgA. We show
      a nearly complete removal of both albumin and IgA from concentrated RBCs via this
      one-step-processes in samples obtained from RBC concentrate. The cell recovery of
      our technology is close to 97%, compared to just above 90% of the current
      procedure of repeated dilution and centrifugation steps. This work clearly shows
      the potential of integrated acoustophoresis in a miniaturized system for clinical
      applications.

PMID- 26315977
TI  - Microporous carbon nanosheets with redox-active heteroatoms for pseudocapacitive
      charge storage.
AB  - We report microporous carbon nanosheets containing numerous redox active
      heteroatoms fabricated from exfoliated waste coffee grounds by simple heating
      with KOH for pseudocapacitive charge storage. We found that various heteroatom
      combinations in carbonaceous materials can be a redox host for lithium ion
      storage. The bio-inspired nanomaterials had unique characteristics, showing
      superior electrochemical performances as cathode for asymmetric pseudocapacitors.

PMID- 26315976
TI  - Novel 5'/3'RACE Method for Amplification and Determination of Single-Stranded
      RNAs Through Double-Stranded RNA (dsRNA) Intermediates.
AB  - To acquire the full-length sequences and to determine the 5'/3'ends of the RNA
      genomes and mRNA transcripts using the rapid amplification of cDNA ends (RACE)
      protocols-via cDNA or mRNA templates-are a great challenge. This 4-steps RNA
      based RACE method uses different ways to determine the RNA ends through a double
      stranded (ds) RNA intermediate (dsRNA-RACE). In the first step a complementary
      RNA strand is synthesised by Phi6 RNA replicase enzyme next to the template ssRNA
      forming a dsRNA intermediate. The following steps include adapter ligation,
      nucleic acid purification and two classical methods with minor modifications
      reverse transcription and polymerase chain reaction. The dsRNA-RACE protocol
      could be used in wide variety of ssRNA (cellular, viral, bacterial, etc.)
      templates in the field of microbiology and cellular biology and suitable for the
      amplification of full-length RNAs including the 5'/3'ends. This is a novel,
      expansively utilizable molecular tool with fewer disadvantages than the existing
      5'/3'RACE approaches. 

PMID- 26315978
TI  - Measurement-Based Care Versus Standard Care for Major Depression: A Randomized
      Controlled Trial With Blind Raters.
AB  - OBJECTIVE: The authors compared measurement-based care with standard treatment in
      major depression. METHODS: Outpatients with moderate to severe major depression
      were consecutively randomized to 24 weeks of either measurement-based care
      (guideline- and rating scale-based decisions; N=61), or standard treatment
      (clinicians' choice decisions; N=59). Pharmacotherapy was restricted to
      paroxetine (20-60 mg/day) or mirtazapine (15-45 mg/day) in both groups.
      Depressive symptoms were measured with the Hamilton Depression Rating Scale (HAM
      D) and the Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR).
      Time to response (a decrease of at least 50% in HAM-D score) and remission (a HAM
      D score of 7 or less) were the primary endpoints. Outcomes were evaluated by
      raters blind to study protocol and treatment. RESULTS: Significantly more
      patients in the measurement-based care group than in the standard treatment group
      achieved response (86.9% compared with 62.7%) and remission (73.8% compared with
      28.8%). Similarly, time to response and remission were significantly shorter with
      measurement-based care (for response, 5.6 weeks compared with 11.6 weeks, and for
      remission, 10.2 weeks compared with 19.2 weeks). HAM-D scores decreased
      significantly in both groups, but the reduction was significantly larger for the
      measurement-based care group (-17.8 compared with -13.6). The measurement-based
      care group had significantly more treatment adjustments (44 compared with 23) and
      higher antidepressant dosages from week 2 to week 24. Rates of study
      discontinuation, adverse effects, and concomitant medications did not differ
      between groups. CONCLUSIONS: The results demonstrate the feasibility and
      effectiveness of measurement-based care for outpatients with moderate to severe
      major depression, suggesting that this approach can be incorporated in the
      clinical care of patients with major depression.

PMID- 26315979
TI  - Gene-Environment Interaction in Youth Depression: Replication of the 5-HTTLPR
      Moderation in a Diverse Setting.
AB  - OBJECTIVE: Replication of scientific findings is a major challenge in biomedical
      research. In psychiatry, the identification of measured gene-environment
      interactions (G*E) has promoted a heated debate over the past decade, with
      controversial results about its influence on disorders such as major depression.
      The authors sought to replicate a 2003 study on G*E in youth depression in a
      large birth cohort from a diverse setting. METHOD: Using data from the 1993
      Pelotas Birth Cohort Study, and adopting a design as similar as possible to that
      of the original study, the authors tested whether the relationship between
      childhood maltreatment and a subsequent depressive episode diagnosis was
      moderated by 5-HTTLPR genotype. Of 5,249 individuals assessed at birth and
      followed up to age 18, data on the evaluation for depressive episodes in early
      adulthood, on childhood maltreatment, and on genotype were available for 3,558
      participants, of whom 2,392 remained after conservative screening for previous
      depressive symptoms. Associations were investigated with logistic regression
      analyses and controlling for potential confounders. RESULTS: The results
      replicated important findings of the original study, this time in a sample of
      young adults from a middle-income country: there was a differential dose-response
      relationship between childhood maltreatment and major depression according to 5
      HTTLPR genotype. CONCLUSIONS: After following a research strategy as comparable
      as possible to that of the original study, the results corroborated the existence
      of a measured G*E, now in a large sample from a different sociocultural context.
      These findings provide further evidence that a genetic variant in the 5-HTTLPR
      moderates the link between childhood maltreatment and youth depression.

PMID- 26315980
TI  - Baseline Striatal Functional Connectivity as a Predictor of Response to
      Antipsychotic Drug Treatment.
AB  - OBJECTIVE: Clinical response to antipsychotic drug treatment is highly variable,
      yet prognostic biomarkers are lacking. The authors recently demonstrated that
      successful antipsychotic drug treatment alters resting-state functional
      connectivity of the striatum. The goal of the present study was to test whether
      intrinsic striatal connectivity patterns provide prognostic information and can
      serve as a potential biomarker of treatment response to antipsychotic drugs.
      METHOD: The authors used resting-state functional MRI (fMRI) to develop a
      prognostic index in a discovery cohort of 41 first-episode schizophrenia
      patients, then tested this index in an independent cohort of 40 newly
      hospitalized chronic patients with acute psychosis. In the discovery cohort,
      patients underwent resting-state fMRI scanning at the initiation of randomized
      controlled treatment with a second-generation antipsychotic. Whole-brain
      functional connectivity maps were generated for each subject from striatal seed
      regions. A stringent measure of clinical response was calculated that required
      sustained improvement over two consecutive study visits. Clinical response was
      entered into a survival analysis, and Cox regression was applied to the
      functional connectivity data. A striatal connectivity index was created,
      comprising functional connections of the striatum that predicted treatment
      response. This striatal connectivity index was tested on a generalizability
      cohort of patients with psychotic disorders who were hospitalized for an acute
      psychotic episode. RESULTS: A total of 91 regions functionally connected with the
      striatum provided significant prognostic information. Connectivity in these
      regions was used to create a baseline striatal connectivity index that predicted
      response to antipsychotic treatment with high sensitivity and specificity in both
      the discovery and generalizability cohorts. CONCLUSIONS: These results provide
      evidence that individual differences in striatal functional connectivity predict
      response to antipsychotic drug treatment in acutely psychotic patients. With
      further development, this has the potential to serve as a prognostic biomarker
      with clinical utility and to reduce the overall burden associated with psychotic
      illnesses.

PMID- 26315981
TI  - Extended-Release Guanfacine for Hyperactivity in Children With Autism Spectrum
      Disorder.
AB  - OBJECTIVE: Hyperactivity, impulsiveness, and distractibility are common problems
      in children with autism spectrum disorder (ASD). Extended-release guanfacine is
      approved for children with attention deficit hyperactivity disorder but not well
      studied in ASD. METHOD: In a multisite, randomized clinical trial, extended
      release guanfacine was compared with placebo in children with ASD accompanied by
      hyperactivity, impulsiveness, and distractibility. RESULTS: Sixty-two subjects
      (boys, N=53; girls, N=9; mean age=8.5 years [SD=2.25]) were randomly assigned to
      guanfacine (N=30) or placebo (N=32) for 8 weeks. The guanfacine group showed a
      43.6% decline in scores on the Aberrant Behavior Checklist-hyperactivity subscale
      (least squares mean from 34.2 to 19.3) compared with a 13.2% decrease in the
      placebo group (least squares mean from 34.2 to 29.7; effect size=1.67). The rate
      of positive response (much improved or very much improved on the Clinical Global
      Impression-Improvement scale) was 50% (15 of 30) for guanfacine compared with
      9.4% (3 of 32) for placebo. A brief cognitive battery tapping working memory and
      motor planning showed no group differences before or after 8 weeks of treatment.
      The modal dose of guanfacine at week 8 was 3 mg/day (range: 1-4 mg/day), and the
      modal dose was 3 mg/day (range: 2-4 mg/day) for placebo. Four guanfacine-treated
      subjects (13.3%) and four placebo subjects (12.5%) exited the study before week
      8. The most common adverse events included drowsiness, fatigue, and decreased
      appetite. There were no significant changes on ECG in either group. For subjects
      in the guanfacine group, blood pressure declined in the first 4 weeks, with
      return nearly to baseline by endpoint (week 8). Pulse rate showed a similar
      pattern but remained lower than baseline at endpoint. CONCLUSIONS: Extended
      release guanfacine appears to be safe and effective for reducing hyperactivity,
      impulsiveness, and distractibility in children with ASD.

PMID- 26315982
TI  - Association Between ADHD and Obesity: A Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: Impulsivity and inattention related to attention deficit hyperactivity
      disorder (ADHD) may increase food intake and, consequently, weight gain. However,
      findings on the association between obesity/overweight and ADHD are mixed. The
      authors conducted a meta-analysis to estimate this association. METHOD: A broad
      range of databases was searched through Aug. 31, 2014. Unpublished studies were
      also obtained. Study quality was rated with the Newcastle-Ottawa Scale. Random
      effects models were used. RESULTS: Forty-two studies that included a total of
      728,136 individuals (48,161 ADHD subjects; 679,975 comparison subjects) were
      retained. A significant association between obesity and ADHD was found for both
      children (odds ratio=1.20, 95% CI=1.05-1.37) and adults (odds ratio=1.55, 95%
      CI=1.32-1.81). The pooled prevalence of obesity was increased by about 70% in
      adults with ADHD (28.2%, 95% CI=22.8-34.4) compared with those without ADHD
      (16.4%, 95% CI=13.4-19.9), and by about 40% in children with ADHD (10.3%, 95%
      CI=7.9-13.3) compared with those without ADHD (7.4%, 95% CI=5.4-10.1). The
      significant association between ADHD and obesity remained when limited to studies
      1) reporting odds ratios adjusted for possible confounding factors; 2) diagnosing
      ADHD by direct interview; and 3) using directly measured height and weight.
      Gender, study setting, study country, and study quality did not moderate the
      association between obesity and ADHD. ADHD was also significantly associated with
      overweight. Individuals medicated for ADHD were not at higher risk of obesity.
      CONCLUSIONS: This study provides meta-analytic evidence for a significant
      association between ADHD and obesity/overweight. Further research should address
      possible underlying mechanisms and the long-term effects of ADHD treatments on
      weight in individuals with both ADHD and obesity.

PMID- 26315983
TI  - Finding the Elusive Psychiatric "Lesion" With 21st-Century Neuroanatomy: A Note
      of Caution.
AB  - The widespread use of MRI has led to a wealth of structural and functional
      anatomical findings in patients with diverse psychiatric disorders that may
      represent insights into pathobiology. However, recent technical reports indicate
      that data from popular MRI research-particularly structural MRI, resting--state
      functional MRI, and diffusion tensor imaging--are highly sensitive to common
      artifacts (e.g., head motion and breathing effects) that may dominate the
      results. Because these and other important confounders of MRI data (e.g.,
      smoking, body weight, metabolic variations, medical comorbidities, psychoactive
      drugs, alcohol use, mental state) tend to vary systematically between patient and
      control groups, the evidence that findings are neurobiologically meaningful is
      inconclusive and may represent artifacts or epiphenomena of uncertain value. The
      authors caution that uncritically accepting from study to study findings that may
      represent fallacies of all sorts carries the risk of misinforming practitioners
      and patients about biological abnormalities underlying psychiatric illness.

PMID- 26315984
TI  - Isn't It About Time to Employ Measurement-Based Care in Practice?

PMID- 26315985
TI  - 1,2-Phosphaborines: hybrid inorganic/organic P-B analogues of benzene.
AB  - Photolysis of the cyclic phosphine oligomer [PPh]5 in the presence of
      pentaarylboroles leads to the formation of 1,2-phosphaborines by the formal
      insertion of a phenylphosphinidene fragment into the endocyclic C?B bond. The
      solid-state structure features a virtually planar central ring with bond lengths
      indicating significant delocalization. Appreciable ring current in the 1,2
      phosphaborine core, detected in nuclear independent chemical shift (NICS)
      calculations, are consistent with aromatic character. These products are the
      first reported 1,2-BPC4 conjugated heterocycles and open a new avenue for B?P as
      a valence isoelectronic substitute for C?C in arene systems. 

PMID- 26315986
TI  - Clinical Impact of Coexisting Patellofemoral Osteoarthritis in Japanese Patients
      With Medial Knee Osteoarthritis.
AB  - OBJECTIVE: To evaluate the clinical impact in knee osteoarthritis (OA) of
      coexisting patellofemoral (PF) joint OA (PFOA) in Japanese patients with medial
      tibiofemoral (TF) joint OA (TFOA). METHODS: Patients with medial knee OA (n =
      143) were enrolled. The radiographic severity of the TF and PF joints, anatomic
      axis angle of the TF joint, patellar alignment, trochlear morphology, patellar
      height, and passive range of motion (ROM) of the painful knee were evaluated.
      Additionally, the Japanese Knee Osteoarthritis Measure (JKOM) was used to
      investigate the association between the presence of PFOA and clinical symptoms.
      RESULTS: PFOA was present in 98 of 143 patients (68.5%) with medial knee OA.
      Quantile regression analysis revealed that coexisting PFOA was associated with
      the pain-related subcategory of the JKOM. Furthermore, multiple logistic
      regression analysis showed that coexisting PFOA was associated with higher odds
      of reporting knee pain on using stairs while ascending (odds ratio [OR] 4.81 [95%
      confidence interval (95% CI) 1.73, 14.3]) and descending (OR 3.86 [95% CI 1.44,
      10.8]). A more varus knee alignment and lower knee flexion ROM, which are
      features of patients with coexisting PFOA, were associated with knee pain while
      ascending/descending stairs. However, patellar alignment, trochlear morphology,
      and patellar height were not significantly associated with knee pain. CONCLUSION:
      PFOA coexisting with medial knee OA was associated with worse clinical symptoms,
      particularly while ascending/descending stairs, although patellar alignment did
      not contribute to reporting knee pain. Further studies that include evaluation of
      the PF joint are warranted to develop a basis for an optimal intervention based
      on compartmental involvement.

PMID- 26315988
TI  - Implications of human value shift and persistence for biodiversity conservation.
AB  - Large-scale change in human values and associated behavior change is believed by
      some to be the ultimate solution to achieve global biodiversity conservation. Yet
      little is known about the dynamics of values. We contribute to this area of
      inquiry by examining the trajectory of values affecting views of wildlife in
      North America. Using data from a 19-state study in the United States and global
      data from the Schwartz Value Survey, we explored questions of value persistence
      and change and the nature of attitudinal responses regarding wildlife
      conservation issues. We found support, based on subjects' ancestry, for the
      supposition that domination is a prevalent American value orientation toward
      wildlife that has origins in European Judeo-Christian traditions. Independent of
      that effect, we also found indications of change. Modernization is contributing
      to a shift from domination to mutualism value orientations, which is fostering
      attitudes less centered on human interests and seemingly more consistent with a
      biocentric philosophy. Our findings suggest that if value shift could be achieved
      in a purposeful way, then significant and widespread behavior change believed
      necessary for long-term conservation success may indeed be possible. In
      particular, greater emphasis on mutualism values may help provide the context for
      more collaborative approaches to support future conservation efforts. However,
      given the societal forces at play, it is not at all clear that human-engineered
      value shift is tenable. Instead of developing strategies aimed at altering
      values, it may be more productive to create strategies that recognize and work
      within the boundaries of existing values. Whereas values appear to be in a period
      of flux, it will be difficult to predict future trends without a better
      understanding of value formation and shift, particularly under conditions of
      rapid social-ecological change. 

PMID- 26315989
TI  - Could gut microbiota protect against sclerosing cholangitis?

PMID- 26315987
TI  - A decade of metaproteomics: where we stand and what the future holds.
AB  - We are living through exciting times during which we are able to unravel the
      "microbial dark matter" in and around us through the application of high
      resolution "meta-omics". Metaproteomics offers the ability to resolve the major
      catalytic units of microbial populations and thereby allows the establishment of
      genotype-phenotype linkages from in situ samples. A decade has passed since the
      term "metaproteomics" was first coined and corresponding analyses were carried
      out on mixed microbial communities. Since then metaproteomics has yielded many
      important insights into microbial ecosystem function in the various environmental
      settings where it has been applied. Although initial progress in analytical
      capacities and resulting numbers of proteins identified was extremely fast, this
      trend slowed rapidly. Here, we discuss several representative metaproteomic
      investigations of activated sludge, acid mine drainage biofilms, freshwater and
      seawater microbial communities, soil, and human gut microbiota. By using these
      case studies, we highlight current challenges and possible solutions for
      metaproteomics to realize its full potential, i.e. to enable conclusive links
      between microbial community composition, physiology, function, interactions,
      ecology, and evolution in situ. 

PMID- 26315990
TI  - Wall characteristics and mechanisms of ischaemic stroke in patients with
      atherosclerotic middle cerebral artery stenosis: a high-resolution MRI study.
AB  - OBJECTIVE: To evaluate the characteristics of atherosclerotic middle cerebral
      artery (MCA) stenosis by high-resolution magnetic resonance imaging (HR-MRI) and
      determine the relationship between wall characteristics and infarction patterns.
      METHODS: Thirty-six patients with acute ischaemic stroke due to MCA stenosis
      underwent diffusion-weighted magnetic resonance imaging (DWI) and HR MRI. Wall
      characteristics of MCA, including irregular surface, superior location, T2
      hyperintense of plaques and positive remodelling (PR), were analysed.
      Characteristics of acute infarct on DWI were categorised according to the number
      (single or multiple infarcts) and the pattern of cerebral infarcts (cortical,
      border zone or perforating artery territory infarcts). The relationship between
      wall characteristics and infarction patterns was evaluated. RESULTS: PR was
      observed in 20 patients, irregular surface plaque in 18 patients, superior
      location of plaques in 14 patients and T2-hyperintense foci in 13 patients.
      Seventeen patients had multiple acute cerebral infarcts and 13 showed single
      acute cerebral infarcts. Border zone infarcts were the most common (76.5%) among
      multiple acute infarcts. Penetrating artery infarcts (PAI) accounted for 76.9% of
      all single infarcts. Multiple infarcts were more frequently observed in patients
      with PR (P =  0.007) or plaque surface irregularity (P =  0.035). Single
      infarcts, especially PAI, were more prevalent in patients with superior plaque (P
      =  0.030). No statistically significant differences were observed between
      multiple and single infarcts in patients with T2-hyperintense lesions (P =
      0.638). CONCLUSIONS: PR or irregular surface plaques were associated with artery
      to-artery embolism. Superior location of plaques was associated with PAI. HR-MRI
      provides insights into intracranial atherosclerosis in vivo, predictive of
      infarction patterns.

PMID- 26315991
TI  - Analysis of POU5F1, c-Kit, PLAP, AP2gamma and SALL4 in gonocytes of patients with
      cryptorchidism.
AB  - Cryptorchidism is a risk factor for the development of testicular germ cell
      tumors (TGCTs). The most common type of TGCT in cryptorchidism is seminoma. The
      intratubular germ cell neoplasia unclassified (ITGCNU) is a histological pattern
      preceding the development of seminomas and non-seminomas. It was suggested that
      in patients with cryptorchidism, the gonocytes remained undifferentiated with
      pluripotent abilities expressing proteins like POU domain class 5 transcription
      factor 1 (POU5F1), tyrosine kinase receptor c-Kit, placental-like alkaline
      phosphatase (PLAP), the transcription factor AP2gamma and sal-like protein 4
      (SALL4) that confer to the gonocytes this ability and therefore make them
      susceptible to develop ITGCNU. The aim of the present study was to determine if
      the gonocytes of patients with cryptorchidism express POU5F1, c-Kit, PLAP,
      AP2gamma and SALL4 proteins after their differentiation period. Based on this, we
      evaluated samples of testicular tissue from newborns to 16-year old subjects with
      or without cryptorchidism in search of POU5F1, c-Kit, PLAP, AP2gamma and SALL4
      using immunocytochemical method, the results of which were validated by RT-PCR.
      The results showed that control subjects witnessed a down-regulation in the
      expression of these five proteins in the first year of life, which eventually
      disappeared. On the other hand, it was determined that 21.6% (8/37) of the
      patients with cryptorchidism continued to express, at least, one of the proteins
      analyzed in this study after the second year of life. And only 5.4% (2/37) of the
      patients were positive to the five markers. These data sustain the proposed
      hypothesis that in cryptorchid patients, ITGCNU arises from gonocytes that fail
      in their differentiation process to spermatogonia with conservation of the
      proteins (POU5F1, c-Kit, PLAP, AP2gamma and SALL4) that maintain pluripotency and
      undifferentiated characteristics and which are responsible for making the
      gonocytes susceptible to malignancy. However, we cannot guarantee that these
      patients present neoplastic transformation. 

PMID- 26315992
TI  - Vitamin E supplementation ameliorates aflatoxin B1-induced nephrotoxicity in
      rats.
AB  - Fungal toxins in nutrition can cause organ dysfunction or even failure. Aflatoxin
      B1 (AFB1)-induced renal impairment is not sufficiently studied regarding its
      extent and prevention. The aim of this experiment was to study the effect of AFB1
      on renal cortical tissue and whether its possible harmful effect could be
      prevented by the conventional economical antioxidant, vitamin E. Forty rats were
      divided into four groups; I-IV. Group I represented the control while the others
      received vitamin E (Vit E), AFB1 and AFB1+Vit E, respectively. Renal cortex
      specimens were taken from each group after 25 days. Then, specimens were prepared
      for histological study by hematoxlyin and eosin (H&E), Masson's trichrome,
      caspase-3 as well as for ultrastructural examination and oxidative stress
      parameters evaluation. Data were morphometrically and statistically analyzed. In
      AFB1-treated group, focal tubulo-interstitial affection in the form of tubular
      cytoplasmic vacuolation, mitochondrial disruption, numerous lysosomes, marked
      increase in collagen deposition and in caspase-3 expression were observed.
      Glomerular impairment in the form of fusion of podocytes enlarged foot processes
      and thickening of the glomerular basement membrane (GBM) with loss of its
      trilaminar appearance were detected. In the group treated by AFB1+Vit E, there
      were minimal affection of the histological structure of the renal cortex as well
      as significant increase in the anti-oxidative parameters which were significantly
      decreased in the AFB1-treated group. Therefore, Vit E could be considered in wide
      experimental studies to be a first choice antioxidant of high cost-effectiveness
      in prevention of fungal toxins pro-oxidant-induced renal impairment. 

PMID- 26315993
TI  - Asexual sporulation facilitates adaptation: The emergence of azole resistance in
      Aspergillus fumigatus.
AB  - Understanding the occurrence and spread of azole resistance in Aspergillus
      fumigatus is crucial for public health. It has been hypothesized that asexual
      sporulation, which is abundant in nature, is essential for phenotypic expression
      of azole resistance mutations in A. fumigatus facilitating subsequent spread
      through natural selection. Furthermore, the disease aspergilloma is associated
      with asexual sporulation within the lungs of patients and the emergence of azole
      resistance. This study assessed the evolutionary advantage of asexual sporulation
      by growing the fungus under pressure of one of five different azole fungicides
      over seven weeks and by comparing the rate of adaptation between scenarios of
      culturing with and without asexual sporulation. Results unequivocally show that
      asexual sporulation facilitates adaptation. This can be explained by the
      combination of more effective selection because of the transition from a
      multicellular to a unicellular stage, and by increased mutation supply due to the
      production of spores, which involves numerous mitotic divisions. Insights from
      this study are essential to unravel the resistance mechanisms of sporulating
      pathogens to chemical compounds and disease agents in general, and for designing
      strategies that prevent or overcome the emerging threat of azole resistance in
      particular.

PMID- 26315994
TI  - Sublingual immunotherapy for asthma.
AB  - BACKGROUND: Asthma is a common long-term respiratory disease affecting
      approximately 300 million people worldwide. Approximately half of people with
      asthma have an important allergic component to their disease, which may provide
      an opportunity for targeted treatment. Sublingual immunotherapy (SLIT) aims to
      reduce asthma symptoms by delivering increasing doses of an allergen (e.g. house
      dust mite, pollen extract) under the tongue to induce immune tolerance. However,
      it is not clear whether the sublingual delivery route is safe and effective in
      asthma. OBJECTIVES: To assess the efficacy and safety of sublingual immunotherapy
      compared with placebo or standard care for adults and children with asthma.
      SEARCH METHODS: We identified trials from the Cochrane Airways Group Specialised
      Register (CAGR), ClinicalTrials.gov (www.ClinicalTrials.gov), the World Health
      Organization (WHO) trials portal (www.who.int/ictrp/en/) and reference lists of
      all primary studies and review articles. The search is up to date as of 25 March
      2015. SELECTION CRITERIA: We included parallel randomised controlled trials
      (RCTs), irrespective of blinding or duration, that evaluated sublingual
      immunotherapy versus placebo or as an add-on to standard asthma management. We
      included both adults and children with asthma of any severity and with any
      allergen-sensitisation pattern. We included studies that recruited participants
      with asthma, rhinitis, or both, providing at least 80% of trial participants had
      a diagnosis of asthma. DATA COLLECTION AND ANALYSIS: Two review authors
      independently screened the search results for included trials, extracted
      numerical data and assessed risk of bias, all of which were cross-checked for
      accuracy. We resolved disagreements by discussion.We analysed dichotomous data as
      odds ratios (ORs) or risk differences (RDs) using study participants as the unit
      of analysis; we analysed continuous data as mean differences (MDs) or
      standardised mean differences (SMDs) using random-effects models. We rated all
      outcomes using GRADE (Grades of Recommendation, Assessment, Development and
      Evaluation) and presented results in the 'Summary of findings' table. MAIN
      RESULTS: Fifty-two studies met our inclusion criteria, randomly assigning 5077
      participants to comparisons of interest. Most studies were double-blind and
      placebo-controlled, but studies varied in duration from one day to three years.
      Most participants had mild or intermittent asthma, often with co-morbid allergic
      rhinitis. Eighteen studies recruited only adults, 25 recruited only children and
      several recruited both or did not specify (n = 9).With the exception of adverse
      events, reporting of outcomes of interest to this review was infrequent, and
      selective reporting may have had a serious effect on the completeness of the
      evidence. Allocation procedures generally were not well described, about a
      quarter of the studies were at high risk of bias for performance or detection
      bias or both and participant attrition was high or unknown in around half of the
      studies.One short study reported exacerbations requiring a hospital visit and
      observed no adverse events. Five studies reported quality of life, but the data
      were not suitable for meta-analysis. Serious adverse events were infrequent, and
      analysis using risk differences suggests that no more than 1 in 100 are likely to
      suffer a serious adverse event as a result of treatment with SLIT (RD 0.0012, 95%
      confidence interval (CI) -0.0077 to 0.0102; participants = 2560; studies = 22;
      moderate-quality evidence).Within secondary outcomes, wide but varied reporting
      of largely unvalidated asthma symptom and medication scores precluded meaningful
      meta-analysis; a general trend suggested SLIT benefit over placebo, but variation
      in scales meant that results were difficult to interpret.Changes in inhaled
      corticosteroid use in micrograms per day (MD 35.10 mcg/d, 95% CI -50.21 to
      120.42; low-quality evidence), exacerbations requiring oral steroids (studies =
      2; no events) and bronchial provocation (SMD 0.69, 95% CI -0.04 to 1.43; very low
      quality evidence) were not often reported. This led to many imprecise estimates
      with wide confidence intervals that included the possibility of both benefit and
      harm from SLIT.More people taking SLIT had adverse events of any kind compared
      with control (OR 1.70, 95% CI 1.21 to 2.38; low-quality evidence; participants =
      1755; studies = 19), but events were usually reported to be transient and
      mild.Lack of data prevented most of the planned subgroup and sensitivity
      analyses. AUTHORS' CONCLUSIONS: Lack of data for important outcomes such as
      exacerbations and quality of life and use of different unvalidated symptom and
      medication scores have limited our ability to draw a clinically useful
      conclusion. Further research using validated scales and important outcomes for
      patients and decision makers is needed so that SLIT can be properly assessed as
      clinical treatment for asthma. Very few serious adverse events have been
      reported, but most studies have included patients with intermittent or mild
      asthma, so we cannot comment on the safety of SLIT for those with moderate or
      severe asthma. SLIT is associated with increased risk of all adverse events.

PMID- 26315995
TI  - A quantitative review of healthcare professionals' questions to a local
      immunization advice service: 4299 enquiries from 3 years.
AB  - BACKGROUND: Immunization advice services can support health professionals by
      providing rapid access to accurate and reliable current information and advice.
      The Vaccine Advice for Clinicians Service (VACCSline) is a service for health
      professionals working within the Thames Valley Area of the UK. METHODS: We
      reviewed all 4299 enquiries received by VACCSline over 3 years. Queries were
      summarized by vaccine type and topic of enquiry. Associations with profession and
      workplace of the enquirer were tested using Fisher's exact tests. RESULTS:
      Incomplete immunization status and non-UK schedules were the most common topics
      of enquiry. Practice nurses were the main service users followed by doctors.
      Enquiries varied by professional role. Alterations to the immunization programme
      led to temporary changes to enquiry content and some more persistent adjustments
      in the balance of enquiries were identified, such as an increase in enquiries
      relating to vaccination in pregnancy. CONCLUSIONS: The content of enquiries to
      VACCSline is broad, confirming the need for immunizers to have a wide knowledge
      base and access to specialist advice to assist with complex scenarios. Systematic
      data capture provided intelligence to guide training and materials to support
      immunizers. A wider networked application of this approach could improve support
      for immunizers.

PMID- 26315996
TI  - A retrospective evaluation of the NHS Health Check Programme in a multi-ethnic
      population.
AB  - BACKGROUND: The NHS Health Check Programme was introduced in 2009 to improve
      primary prevention of coronary heart disease, stroke, diabetes and chronic kidney
      disease; however, there has been debate regarding the impact. We present a
      retrospective evaluation of Leicester City Clinical Commissioning Group. METHODS:
      Data are reported on diagnosis of type 2 diabetes, hypertension, chronic kidney
      disease, high risk of type 2 diabetes and high risk of cardiovascular disease.
      Data on management following the Health Check are also reported. RESULTS: Over a
      5-year period, 53 799 health checks were performed, 16 388 (30%) people were
      diagnosed with at least one condition when diagnosis of being at high risk of
      cardiovascular disease was defined as >=20%. This figure increased to 43% when
      diagnosis of high cardiovascular risk >=10% was included. Of the 3063 (5.7%)
      individuals diagnosed with type 2 diabetes, 54% were prescribed metformin and 26%
      were referred for structured education. Of the 5797 (10.8%) individuals diagnosed
      at high risk of cardiovascular disease (>=20%), 64% were prescribed statins.
      CONCLUSIONS: A high proportion of new cases of people at risk of cardiovascular
      disease were identified by the NHS Health Check Programme. Data suggest that this
      has translated into appropriate preventative measures.

PMID- 26315997
TI  - The impact of chronic blackberry intake on the neuroinflammatory status of rats
      fed a standard or high-fat diet.
AB  - Neuroinflammation has been suggested as a central mediator of central nervous
      system dysfunction, including in dementia and neurodegenerative disease.
      Flavonoids have emerged as promising candidates for the prevention of
      neurodegenerative diseases and are thought to be capable of antiinflammatory
      effects in the brain. In the present study, the impact of a chronic intake of an
      anthocyanin extract from blackberry (BE) on brain inflammatory status in the
      presence or absence of a high-fat diet was investigated. Following intake of the
      dietary regimes for 17 weeks neuroinflammatory status in Wistar rat cortex,
      hippocampus and plasma were assessed using cytokine antibody arrays. In the
      cortex, intake of the high-fat diet resulted in an increase of at least 4-fold,
      in expression of the cytokine-induced neutrophil chemoattractant CINC-3, the
      ciliary neurotrophic factor CNTF, the platelet-derived growth factor PDGF-AA, IL
      10, the tissue inhibitor of metalloproteinase TIMP-1 and the receptor for
      advanced glycation end products RAGE. BE intake partially decreased the
      expression of these mediators in the high-fat challenged brain. In standard-fed
      animals, BE intake significantly increased cortical levels of fractalkine, PDGF
      AA, activin, the vascular endothelial growth factor VEGF and agrin expression,
      suggesting effects as neuronal growth and synaptic connection modulators. In
      hippocampus, BE modulates fractalkine and the thymus chemokine TCK-1 expression
      independently of diet intake and, only in standard diet, increased PDGF-AA.
      Exploring effects of anthocyanins on fractalkine transcription using the neuronal
      cell line SH-SY5Y suggested that other cell types may be involved in this effect.
      This is the first evidence, in in vivo model, that blackberry extract intake may
      be capable of preventing the detrimental effects of neuroinflammation in a high
      fat challenged brain. Also, fractalkine and TCK-1 expression may be specific
      targets of anthocyanins and their metabolites on neuroinflammation.

PMID- 26315999
TI  - Erratum to: Evaluation of BLAST-based edge-weighting metrics used for homology
      inference with the Markov Clustering algorithm.

PMID- 26315998
TI  - Genetic association between TRAIL-R1 Thr209Arg and cancer susceptibility.
AB  - We aimed to determine the indecisive association between tumor necrosis factor
      related apoptosis-inducing ligand receptor 1 (TRAIL-R1) Thr209Arg polymorphism
      and inherited susceptibility to cancer. A meta-analysis combining data on 9,517
      individuals was performed to assess the association between TRAIL-R1 Thr209Arg
      and cancer incidence. The summary ORs with 95% CI calculated with the fixed
      effects model suggested that Thr209Arg was not significantly associated with
      cancer susceptibility (homozygous model: OR 0.98, 95% CI 0.88-1.09; heterozygous
      model: OR 0.95, 95% CI 0.87-1.04; allele frequency model: OR 0.99, 95% CI 0.94
      1.05; dominant model: OR 0.98, 95% CI 0.91-1.05; recessive model: OR 1.01, 95% CI
      0.92-1.10). Stratified analysis by ethnicity and cancer type yielded similar null
      associations. These statistical data suggest that Thr209Arg in exon 4 of the
      TRAIL-R1 gene may not represent a modifier of susceptibility to cancer. 

PMID- 26316002
TI  - No justice in sight: The mental health and wellbeing of West Papuan refugees.

PMID- 26316003
TI  - Keep calm: Psychiatric disorders are organic! The power of words in medicine.

PMID- 26316004
TI  - Immune activation as a mediator of the gut-brain axis in manic episodes.

PMID- 26316005
TI  - Clinical outcomes of esophageal stents in patients with malignant esophageal
      obstruction according to palliative additional treatment.
AB  - OBJECTIVE: To evaluate the efficacy and feasibility of esophageal self-expanding
      metal stents (SEMS) insertion for malignant esophageal obstruction (MEO) in
      patients with or without additional palliative treatment. METHODS: We
      retrospectively reviewed the medical records of the patients with SEMS for MEO.
      Baseline characteristics, changes in Mellow-Pinkas dysphagia score, and adverse
      events were collected and compared according to the presence and absence of
      additional palliative treatment. RESULTS: Altogether 192 patients underwent 236
      SEMS insertion procedures. Esophageal, gastric cardiac and lung cancers were seen
      in 46.4%, 33.3% and 15.1% of the patients, respectively. Their Mellow-Pinkas
      score significantly decreased within one week and one month after the SEMS
      insertion (1.66 +/- 0.79 and 1.71  +/-  0.87 vs 3.09  +/-  0.79, respectively, P
      =  0.000). Complications occurred in 54 (22.9%) of 236 SEMS insertion; there were
      28 (11.9%) stent obstruction, 5 (2.1%) perforation (2.1%), 10 (4.2%) stent
      migration, 5 (2.1%) tracheoesophageal fistula, but no procedure-related death.
      Most complications were managed by inserting additional SEMS. The risk of stent
      obstruction was significantly higher in uncovered stents than in covered SEMS (OR
      3.56, 95% CI 1.39-9.12, P = 0.006). Mean duration to the development of
      complications was 74.8 +/- 111.1 days. Overall survival (169.0 +/- 127.8 days vs
      96.4 +/- 90.6 days, P = 0.000) and stent patency (143.3 +/- 123.9 days vs 67.6 +/
      71.3 days, P = 0.000) were significantly favorable in patients with SEMS and
      additional palliative treatments compared with those with SEMS alone. CONCLUSION:
      SEMS insertion is effective and safe for treating MEO, and additional palliative
      treatment might lengthen stent patency by prolonging the patient's survival.

PMID- 26316006
TI  - Barriers to Providing Health Education During Primary Care Visits at Community
      Health Centers: Clinical Staff Insights.
AB  - The rapid increase of diverse patients living in the US has created a different
      set of needs in healthcare, with the persistence of health disparities continuing
      to challenge the current system. Chronic disease management has been discussed as
      a way to improve health outcomes, with quality patient education being a key
      component. Using a community based participatory research framework, this study
      utilized a web-based survey and explored clinical staff perceptions of barriers
      to providing patient education during primary care visits. With a response rate
      of nearly 42 %, appointment time allotment seemed to be one of the most critical
      factors related to the delivery of health education and should be considered key.
      The importance of team-based care and staff training were also significant.
      Various suggestions were made in order to improve the delivery of quality patient
      education at community health centers located in underserved areas.

PMID- 26316007
TI  - Rural Family Perspectives and Experiences with Early Infant Hearing Detection and
      Intervention: A Qualitative Study.
AB  - Infant hearing loss has the potential to cause significant communication
      impairment. Timely diagnosis and intervention is essential to preventing
      permanent deficits. Many infants from rural regions are delayed in diagnosis and
      treatment of hearing loss. The purpose of this study is to characterize the
      barriers in timely infant hearing healthcare for rural families following newborn
      newborn hearing screening (NHS) testing. Using stratified purposeful sampling,
      the study design involved semi-structured phone interviews with parents/guardians
      of children who failed NHS testing in the Appalachian region of Kentucky between
      2012 and 2014 to describe their experiences with early hearing detection and
      intervention program. Thematic qualitative analysis was performed on interview
      transcripts to identify common recurring themes in content. 40 parents/guardians
      participated in the study and consisted primarily of mothers. Demographic data
      revealed limited educational levels of the participants and 70 % had state-funded
      insurance coverage. Participants reported barriers in timely infant hearing
      healthcare that included poor communication of hearing screening results,
      difficulty in obtaining outpatient testing, inconsistencies in healthcare
      information from primary care providers, lack of local resources, insurance
      related healthcare delays, and conflict with family and work responsibilities.
      Most participants expressed a great desire to obtain timely hearing healthcare
      for their children and expressed a willingness to use resources such as
      telemedicine to obtain that care. There are multiple barriers to timely rural
      infant hearing healthcare. Minimizing misinformation and improving access to care
      are priorities to prevent delayed diagnosis and treatment of hearing loss.

PMID- 26316008
TI  - Central line-associated bloodstream infections among critically-ill patients in
      the era of bundle care.
AB  - BACKGROUND/PURPOSE: Patients admitted to intensive care units (ICUs) are at high
      risk for central line-associated bloodstream infections (CLABSIs). Bundle care
      has been documented to reduce CLABSI rates in Western countries, however, few
      reports were from Asian countries and the differences in the epidemiology or
      outcomes of critically-ill patients with CLABSIs after implementation of bundle
      care remain unknown. We aimed to evaluate the incidence, microbiological
      characteristics, and factors associated with mortality in critically-ill patients
      after implementation of bundle care. METHODS: Prospective surveillance was
      performed on patients admitted to ICUs at the National Taiwan University
      Hospital, Taipei, Taiwan from January 2012 to June 2013. The demographic,
      microbiological, and clinical data of patients who developed CLABSI according to
      the National Healthcare Safety Network definition were reviewed. A total of 181
      episodes of CLABSI were assessed in 156 patients over 46,020 central-catheter
      days. RESULTS: The incidence of CLABSI was 3.93 per 1000 central-catheter days.
      The predominant causative microorganisms isolated from CLABSI episodes were Gram
      negative bacteria (39.2%), followed by Gram-positive bacteria (33.2%) and Candida
      spp. (27.6%). Median time from insertion of a central catheter to occurrence of
      CLABSI was 8 days. In multivariate analysis, the independent factors associated
      with mortality were higher Pitt bacteremia score [odds ratio (OR) 1.41; 95%
      confidence interval (CI) 1.18-1.68] and longer interval between onset of CLABSIs
      and catheter removal (OR 1.10; 95% CI 1.02-1.20), respectively. CONCLUSION: In
      institutions with a high proportion of CLABSI caused by Gram-negative bacteria,
      severity of bacteremia and delay in catheter removal were significant factors
      associated with mortality.

PMID- 26316009
TI  - Risk of recurrent nontyphoid Salmonella bacteremia in human immunodeficiency
      virus-infected patients with short-term secondary prophylaxis in the era of
      combination antiretroviral therapy.
AB  - BACKGROUND/PURPOSE: Nontyphoid Salmonella (NTS) bacteremia causes high mortality
      and recurrence rates in human immunodeficiency virus (HIV)-infected patients.
      This study aimed to investigate the risk of recurrent NTS bacteremia in the era
      of combination antiretroviral therapy (cART). METHODS: The medical records of
      consecutive HIV-infected patients with NTS bacteremia from January 2006 to June
      2014 were reviewed. The patients were divided into two groups: patients who
      achieved a decline of plasma HIV RNA load by >= 2 log10 after 4 weeks of cART
      (good short-term virological response) and those who failed to achieve the goal
      (poor short-term virological response). Clinical information was collected on the
      demographics, immunological and virological responses, prophylactic antibiotics
      used, episodes of recurrent NTS bacteremia, and mortality. RESULTS: During the
      study period, 49 patients with 52 episodes of NTS bacteremia were included: 29
      patients in the good virological response group, in which 16 received secondary
      prophylaxis; and 20 patients in the poor response group, in which 15 received
      secondary prophylaxis. There were no recurrent episodes of NTS bacteremia in the
      good-response group, whereas the incidence rate of recurrent NTS bacteremia was
      5.21 per 100 person-years and 56.42 per 100 person-years of follow-up in patients
      receiving and not receiving prophylaxis, respectively, in the poor-response
      group. No patients died in the good-response group, whereas five patients (25%)
      in the poor-response group died. The resistance rate of 52 NTS isolates tested to
      ciprofloxacin was 7.7%. CONCLUSION: The risk of recurrent NTS bacteremia is low
      in HIV-infected patients who achieve short-term virological response to cART,
      regardless of secondary prophylaxis.

PMID- 26316010
TI  - Genetically diverse serotypes III and VI substitute major clonal disseminated
      serotypes Ib and V as prevalent serotypes of Streptococcus agalactiae from 2007
      to 2012.
AB  - BACKGROUND: Streptococcus agalactiae [group B Streptococcus (GBS)] has become
      more prevalent in nonpregnant women, the elderly, and people who are
      immunocompromised. We investigated the serotype and genomic changes of GBS human
      isolates from different hospitals from 2007 to 2012. METHODS: The serotype and
      genotype of 658 GBS human isolates were determined with multiplex polymerase
      chain reaction and pulsed field gel electrophoresis analysis. Multilocus sequence
      typing analysis determined the sequence type (ST) of the major clones of
      serotypes Ib, V, and VI. RESULTS: Most of the isolates were collected from urine
      samples (60.5%) with a reduction in the rate from 74.6% in 2007 to 34.5% in 2012
      and from infected patients older than 30 years (72.6%). The female/male ratio
      differed depending on the source: 3.52 in the urine group, 0.48 in the wound
      group, and 0.43 in pus. Serotypes Ib (16.5%), III (16.9%), V (27.2%), and VI
      (17.6%) were the most predominant among the nine serotypes identified and were
      separated into two prevalence patterns: a decrease in serotypes Ib and V and an
      increase in serotypes III and VI from 2007 to 2012. The prevalence change was
      associated with the urine group. Additionally, serotype VI become more prevalent
      in blood samples in four hospitals. The pulsed field gel electrophoresis analysis
      demonstrated three genetic patterns: limited pulsotypes and a major clonal
      dissemination for serotypes Ib and V, diverse pulsotypes for serotypes III, and
      diverse pulsotypes with a major clonal dissemination for serotype VI. Multilocus
      sequence typing analysis of the major clones identified ST12 for serotype Ib and
      ST1 for serotypes V and VI. CONCLUSION: Rapid genomic variations with different
      evolutionary patterns have led to the establishment of serotypes III and VI as
      the predominant GBS serotypes.

PMID- 26316012
TI  - Functional Changes of Dendritic Cells in C6 Glioma-Bearing Rats That Underwent
      Combined Argon-Helium Cryotherapy and IL-12 Treatment.
AB  - OBJECTIVE: The aim of this study was to explore changes in tumor tissues of
      glioma-bearing rats that underwent argon-helium cryoablation as well as changes
      in antitumor immunity before and after combined interleukin 12 treatment.
      METHODS: Two hundred sixty Wistar rats were randomly divided into a blank control
      group, intravenous injection interleukin-12 group, cryotherapy group, and
      cryotherapy + intravenous injection group. C6 glioma cells proliferated in vitro
      were implanted subcutaneously on the backs of rats to establish C6 glioma-bearing
      animal models. Each group underwent the corresponding treatments, and
      morphological changes in tumor tissues were examined using hematoxylin-eosin
      staining. CD11c staining was examined using immunohistochemistry, and differences
      in dendritic cells and T-cell subsets before and after treatment were analyzed
      using flow cytometry. RESULTS: The control group showed no statistical changes in
      terms of tumor tissue morphology and cellular immunity, cryotherapy group, and
      cryotherapy + intravenous injection group, among which the count for the
      cryotherapy + intravenous injection group was significantly higher than those of
      all other groups. In the argon-helium cryotherapy group, tumor cells were damaged
      and dendritic cell markers were positive. The number of CD11c+ and CD86+ cells
      increased significantly after the operation as did the cytokine interferon-gamma
      level (P < .01), suggesting a shift toward Th1-type immunity. CONCLUSION:
      Combined treatment of argon-helium cryoablation and interleukin 12 for gliomas
      not only effectively injured tumor tissues but also boosted immune function and
      increased antitumor ability. Therefore, this approach is a promising treatment
      measure for brain gliomas.

PMID- 26316011
TI  - Stem cells isolated from human dental pulp and amniotic fluid improve skeletal
      muscle histopathology in mdx/SCID mice.
AB  - INTRODUCTION: Duchenne muscular dystrophy (DMD), caused by a lack of the
      functional structural protein dystrophin, leads to severe muscle degeneration
      where the patients are typically wheelchair-bound and die in their mid-twenties
      from cardiac or respiratory failure or both. The aim of this study was to
      investigate the potential of human dental pulp stem cells (hDPSCs) and human
      amniotic fluid stem cells (hAFSCs) to differentiate toward a skeletal myogenic
      lineage using several different protocols in order to determine the optimal
      conditions for achieving myogenic commitment and to subsequently evaluate their
      contribution in the improvement of the pathological features associated with
      dystrophic skeletal muscle when intramuscularly injected into mdx/SCID mice, an
      immune-compromised animal model of DMD. METHODS: Human DPSCs and AFSCs were
      differentiated toward myogenic lineage in vitro through the direct co-culture
      with a myogenic cell line (C2C12 cells) and through a preliminary demethylation
      treatment with 5-Aza-2'-deoxycytidine (5-Aza), respectively. The commitment and
      differentiation of both hDPSCs and hAFSCs were evaluated by immunofluorescence
      and Western blot analysis. Subsequently, hDPSCs and hAFSCs, preliminarily
      demethylated and pre-differentiated toward a myogenic lineage for 2 weeks, were
      injected into the dystrophic gastrocnemius muscles of mdx/SCID mice. After 1, 2,
      and 4 weeks, the gastrocnemius muscles were taken for immunofluorescence and
      histological analyses. RESULTS: Both populations of cells engrafted within the
      host muscle of mdx/SCID mice and through a paracrine effect promoted angiogenesis
      and reduced fibrosis, which eventually led to an improvement of the
      histopathology of the dystrophic muscle. CONCLUSION: This study shows that hAFSCs
      and hDPSCs represent potential sources of stem cells for translational strategies
      to improve the histopathology and potentially alleviate the muscle weakness in
      patients with DMD.

PMID- 26316013
TI  - A Randomized Trial Comparing Disease Activity Measures for the Assessment and
      Prediction of Response in Rheumatoid Arthritis Patients Initiating Certolizumab
      Pegol.
AB  - OBJECTIVE: The aim of the Patient/Physician Reported Efficacy Determination In
      Clinical Practice Trial (PREDICT; ClinicalTrials identifier NCT01255761) was to
      compare the patient-reported Routine Assessment of Patient Index Data 3 (RAPID-3)
      instrument with the investigator-based Clinical Disease Activity Index (CDAI) for
      assessing certolizumab pegol (CZP) treatment response in rheumatoid arthritis
      patients at 12 weeks and to predict the treatment response at week 52 using the
      data from week 12 (coprimary end points). METHODS: Patients received 400 mg of
      CZP at weeks 0, 2, and 4 (loading dose), followed by 200 mg every 2 weeks
      thereafter. Patients were randomized 1:1 to assessment with the RAPID-3 or the
      CDAI. Responder classification was performed at week 12; treatment response was
      defined as a score of <=6 or a 20% improvement over baseline on the RAPID-3 or a
      score of <=10 or a 20% improvement over baseline on the CDAI. Long-term treatment
      success was defined as a Disease Activity Score in 28 joints using the
      erythrocyte sedimentation rate (DAS28-ESR) of <=3.2 at week 52. Comparisons were
      made for the coprimary end points using noninferiority methods. Patients with
      improvement of <1 on the CDAI score or with no improvement on the RAPID-3 score
      at week 12 or patients with high levels of disease activity (CDAI score >22 or
      RAPID-3 score >12) at 2 consecutive visits were withdrawn from the study.
      RESULTS: Patients had longstanding disease (mean 8.9 years) and high levels of
      disease activity (mean scores of 6.3 on the DAS28-ESR, 16.1 on the RAPID-3, and
      40.2 on the CDAI). Previous anti-tumor necrosis factor therapy had failed in
      55.5% of them. At week 12, a total of 64.7% (by RAPID-3) and 76.4% (by CDAI) of
      the patients were classified as responders (difference of -11.9% [95% confidence
      interval -18.4%, -5.3%]). At week 52, a total of 31.5% (by RAPID-3) and 32.3% (by
      CDAI) of the responders achieved a low level of disease activity on the DAS28-ESR
      (difference of -1.3% [95% confidence interval -9.3%, 6.6%]). CONCLUSION: The CDAI
      classified more patients as CZP responders at week 12 than did the RAPID-3.
      Although these outcome measures were not statistically comparable, the positive
      predictive value for low disease activity at week 52 was similar. As these tools
      cover differing domains of therapy response, further evaluation for clinical
      disease activity assessments and treatment decisions is needed.

PMID- 26316014
TI  - Mathematical Modelling and Prediction of the Effect of Chemotherapy on Cancer
      Cells.
AB  - Cancer is a class of diseases characterized by out-of-control cells' growth which
      affect DNAs and make them damaged. Many treatment options for cancer exist, with
      the primary ones including surgery, chemotherapy, radiation therapy, hormonal
      therapy, targeted therapy and palliative care. Which treatments are used depends
      on the type, location, and grade of the cancer as well as the person's health and
      wishes. Chemotherapy is the use of medication (chemicals) to treat disease. More
      specifically, chemotherapy typically refers to the destruction of cancer cells.
      Considering the diffusion of drugs in cancer cells and fractality of DNA walks,
      in this research we worked on modelling and prediction of the effect of
      chemotherapy on cancer cells using Fractional Diffusion Equation (FDE). The
      employed methodology is useful not only for analysis of the effect of special
      drug and cancer considered in this research but can be expanded in case of
      different drugs and cancers. 

PMID- 26316015
TI  - Frequency of intradialytic hypotensive episodes: old problem, new insights.
AB  - Symptomatic intradialytic hypotension (IDH) continues to be an important
      complication of hemodialysis treatment. There is some evidence that besides an
      IDH episode, repeated episodes could represent an even more important independent
      risk factor for mortality in hemodialysis patients. A retrospective cross
      sectional study was performed to study 18 dialysis treatments in 43 patients
      during 6 weeks. Relationships of IDH episodes with baseline variables were
      examined using a Poisson regression model (generalized linear model). IDH was
      frequent (93% of patients) and highly variable by patient (0%-100%). Multivariate
      analysis showed that patients who experienced frequent hypotensive episodes had a
      lower dry weight (90% confidence interval [CI]: 0.95-0.99), higher phosphorus
      levels (90% CI: 1.07-1.47), greater prevalence of diabetes mellitus (90% CI: 1.11
      2.71), and hypertension (90% CI: 1.04-2.45). Dry weight, hypertension, and
      phosphorus levels are modifiable risk factors to possibly reduce the rate of IDH
      episodes. The potential protective role of phosphorus warrants further
      investigation. 

PMID- 26316016
TI  - Longitudinal evaluation of health-related quality of life after
      osteoradionecrosis of the mandible.
AB  - There is a lack of longitudinal data on the effect of osteoradionecrosis (ORN) on
      health-related quality of life (HRQoL). We report data on HRQoL across groups of
      patients with ORN at different stages of disease and reconstruction. We
      identified 71 patients treated for ORN of the mandible, and cross-referenced the
      data with their medical records. They were divided into 4 groups according to the
      Notani classification and patients who did not have ORN were used for comparison.
      Patients with ORN reported the most pain, and rates were relatively high for
      problems concerning appearance, activity, recreation, swallowing, and chewing.
      There were significant differences for pain, appearance, swallowing, and chewing
      between patients who had ORN and those who did not and had not had radiotherapy.
      On the University of Washington quality of life questionnaire (UWQoL), patients
      with ORN reported similar levels of morbidity to those who had had radiotherapy
      but did not have ORN, particularly on the physical and social-emotional
      subscales. Those with grade III ORN were particularly affected, and the UWQoL
      scores after mandibular resection and reconstruction were disappointing. HRQoL
      after composite resection for Notani grade III disease is relatively poor. In
      patients whose symptoms can be managed without an operation, it seems appropriate
      to defer resection and reconstruction until there is an appreciable drop in the
      quality of life, and pain is difficult to control. 

PMID- 26316017
TI  - Risk of wound infection and safety profile of amoxicillin in healthy patients
      which required third molar surgery: a systematic review and meta-analysis.
AB  - The aim of this systematic review and meta-analysis was to assess the risk of
      surgical wound infection and the adverse effects of amoxicillin in healthy
      patients who required excision of third molars. We identified eligible reports
      from searches of PubMed, Medline(r), the Cochrane Library, Imbiomed, LILACS, and
      Google Scholar. Studies that met our minimum requirements were evaluated using
      inclusion and exclusion criteria and the Oxford Quality Scale. Those with a score
      of 3 or more on this Scale were included and their data were extracted and
      analysed. For evaluation of the risk of infection the absolute risk reduction,
      number needed to treat, and 95% CI were calculated. For evaluation of the risk of
      an adverse effect the absolute risk increase, number needed to harm, and 95% CI
      were calculated using the Risk Reduction Calculator. Each meta-analysis was made
      with the help of the Mantel-Haenszel random effects model, and estimates of risk
      (OR) and 95% CI were calculated using the Review Manager 5.3, from the Cochrane
      Library. A significant risk was assumed when the lower limit of the 95% CI was
      greater than 1. Probabilities of less than 0.05 were accepted as significant. The
      results showed that there was no reduction in the risk of infection when
      amoxicillin was given before or after operation compared with an untreated group
      or placebo. In conclusion, this study suggests that amoxicillin given
      prophylactically or postoperatively does not reduce the risk of infection in
      healthy patients having their third molars extracted. 

PMID- 26316018
TI  - Multiple glass fragments in the periorbital region 43 years after initial injury:
      report of an unusual case.

PMID- 26316019
TI  - In touch to teach: Do nurse educators need to maintain or possess recent clinical
      practice to facilitate student learning?
AB  - In recent years UK university-based nurse educators have seen a reduction in
      their responsibilities for nursing students' practice-based assessments. Many
      university-based nurse educators feel that this lack of input into students'
      clinical assessments leaves them open to criticism as they are perceived to be
      less "in-touch" with clinical practice and that their knowledge to teach nursing
      students is diminished as a result. This paper examines and debates some
      interpretations of the term "recent clinical practice" and challenges the
      misconception among many in the profession, as well as government and
      professional bodies, that university-based nurse educators require recent
      clinical practice to effectively teach students and enhance the student learning
      experience in the academic university setting. 

PMID- 26316020
TI  - The Epidemiology of Human Immunodeficiency Virus Infection and Care among Adult
      and Adolescent Females in the United States, 2008-2012.
AB  - OBJECTIVE: We sought to determine epidemiological patterns in diagnoses of human
      immunodeficiency virus (HIV) infection and prevalence among females by age,
      race/ethnicity and transmission category, and essential steps in the continuum of
      HIV care. METHODS: Using data from the National HIV Surveillance System, we
      estimated the number of females aged 13 years or older diagnosed with HIV
      infection in 2008 through 2012 and living with HIV at the end of 2011 in the
      United States. We determined percentages of females linked to care, retained in
      care, and virally suppressed in 18 jurisdictions with complete reporting of CD4
      and viral load test results. RESULTS: From 2008 to 2012, the estimated rate of
      HIV diagnoses among females decreased from 9.3 to 6.9 per 100,000 (-7.1% per
      year; 95% confidence interval [CI], -7.9, -6.3). In 2012, the diagnosis rate was
      highest among Blacks/African Americans (35.7), followed by Hispanics or Latinos
      (6.4), and Native Hawaiian Other Pacific Islander (5.1), and lowest among Whites
      (1.8). Most females diagnosed in 2012 were linked to care within 3 months of
      diagnosis (82.5%). About one-half (52.4%) of females living with HIV in 2011
      received ongoing care in 2011 and 44.3% had a suppressed viral load. Viral
      suppression was lower among American Indian/Alaska Native (29.7%) and
      Black/African American (41.6%) compared with White females (46.5%). The
      percentage in care and with viral suppression was lower among younger compared
      with older females. CONCLUSION: HIV diagnoses continue to decrease among females;
      however, disparities exist in HIV burden and viral suppression. Improvements in
      care and treatment outcomes are needed for all women with particular emphasis on
      younger women.

PMID- 26316021
TI  - A Novel Designed Bioreactor for Recovering Precious Metals from Waste Printed
      Circuit Boards.
AB  - For recovering precious metals from waste printed circuit boards (PCBs), a novel
      hybrid technology including physical and biological methods was developed. It
      consisted of crushing, corona-electrostatic separation, and bioleaching.
      Bioleaching process is the focus of this paper. A novel bioreactor for
      bioleaching was designed. Bioleaching was carried out using Pseudomonas
      chlororaphis. Bioleaching experiments using mixed particles of Au and Cu were
      performed and leachate contained 0.006 mg/L, 2823 mg/L Au(+) and Cu(2+)
      respectively. It showed when Cu existed, the concentrations of Au were extremely
      small. This provided the feasibility to separate Cu from Au. The method of
      orthogonal experimental design was employed in the simulation bioleaching
      experiments. Experimental results showed the optimized parameters for separating
      Cu from Au particles were pH 7.0, temperature 22.5  degrees C, and rotation speed
      80 r/min. Based on the optimized parameters obtained, the bioreactor was operated
      for recovering mixed Au and Cu particles. 88.1 wt.% of Cu and 76.6 wt.% of Au
      were recovered. The paper contributed important information to recover precious
      metals from waste PCBs. 

PMID- 26316023
TI  - Termite mounds harness diurnal temperature oscillations for ventilation.
AB  - Many species of millimetric fungus-harvesting termites collectively build
      uninhabited, massive mound structures enclosing a network of broad tunnels that
      protrude from the ground meters above their subterranean nests. It is widely
      accepted that the purpose of these mounds is to give the colony a controlled
      microclimate in which to raise fungus and brood by managing heat, humidity, and
      respiratory gas exchange. Although different hypotheses such as steady and
      fluctuating external wind and internal metabolic heating have been proposed for
      ventilating the mound, the absence of direct in situ measurement of internal air
      flows has precluded a definitive mechanism for this critical physiological
      function. By measuring diurnal variations in flow through the surface conduits of
      the mounds of the species Odontotermes obesus, we show that a simple combination
      of geometry, heterogeneous thermal mass, and porosity allows the mounds to use
      diurnal ambient temperature oscillations for ventilation. In particular, the thin
      outer flutelike conduits heat up rapidly during the day relative to the deeper
      chimneys, pushing air up the flutes and down the chimney in a closed convection
      cell, with the converse situation at night. These cyclic flows in the mound flush
      out CO2 from the nest and ventilate the colony, in an unusual example of deriving
      useful work from thermal oscillations. 

PMID- 26316022
TI  - C5orf30 is a negative regulator of tissue damage in rheumatoid arthritis.
AB  - The variant rs26232, in the first intron of the chromosome 5 open reading frame
      30 (C5orf30) locus, has recently been associated with both risk of developing
      rheumatoid arthritis (RA) and severity of tissue damage. The biological
      activities of human C5orf30 are unknown, and neither the gene nor protein show
      significant homology to any other characterized human sequences. The C5orf30 gene
      is present only in vertebrate genomes with a high degree of conservation,
      implying a central function in these organisms. Here, we report that C5orf30 is
      highly expressed in the synovium of RA patients compared with control synovial
      tissue, and that it is predominately expressed by synovial fibroblast (RASF) and
      macrophages in the lining and sublining layer of the tissue. These cells play a
      central role in the initiation and perpetuation of RA and are implicated in
      cartilage destruction. RASFs lacking C5orf30 exhibit increased cell migration and
      invasion in vitro, and gene profiling following C5orf30 inhibition confirmed up
      regulation of genes involved in cell migration, adhesion, angiogenesis, and
      immune and inflammatory pathways. Importantly, loss of C5orf30 contributes to the
      pathology of inflammatory arthritis in vivo, because inhibition of C5orf30 in the
      collagen-induced arthritis model markedly accentuated joint inflammation and
      tissue damage. Our study reveal C5orf30 to be a previously unidentified negative
      regulator of tissue damage in RA, and this protein may act by modulating the
      autoaggressive phenotype that is characteristic of RASFs. 

PMID- 26316024
TI  - Impact of barley form on equine total tract fibre digestibility and colonic
      microbiota.
AB  - This study aimed at assessing the impact of four barley forms on total tract
      apparent digestibility of dietary fibre in horses fed a large amount of starch in
      the morning meal (0.27% BW). Processed barley forms had a greater pre-caecal
      starch digestibility than the whole form. Based on this result, we hypothesised
      that using barley-processing methods would limit the potential dumping of
      undegraded starch in the hindgut of horses and, consequently, the potential
      negative effect on fibre degradation in the hindgut. In a 4*4 latin square
      design, four mature geldings fitted with a right ventral colon-fistula were fed a
      meadow hay : concentrate (62 : 38; dry matter (DM) basis) diet at 1.7% BW. The
      concentrate was made of 80% barley distributed either as whole grain or as
      processed forms: 2.5 mm ground, pelleted or steam-flaked. For each period, total
      tract apparent digestibilities of DM, NDF and ADF were determined over 3
      consecutive days by total faecal collection, whereas pH, volatile fatty acids
      (VFA) concentrations and cultural functional bacteria counts (total anaerobic,
      cellulolytic bacteria, lactic acid producers, amylolytic bacteria and lactic acid
      utilisers) in colonic content were evaluated on 1 day 4 h after the morning meal.
      Total tract apparent digestibility of DM and dietary fibre was influenced
      (P<0.05) by barley form. Diets including thermo-mechanically treated barley forms
      led to a higher (P<0.05) total tract apparent digestibility of NDF than those
      constituted of ground barley and also led to a greater (P<0.05) total tract
      apparent digestibility of ADF than those made of whole or ground barley forms.
      However, no significant difference was observed in colonic pH, VFA concentrations
      and cultural bacteria concentrations. Owing to a high starch supply in the
      morning meal, the concentration of the functional bacteria in the colonic content
      averaged 7.8 log CFU/ml, 5.9 NPM/ml, 6.9 and 7.3 CFU/ml for total anaerobic,
      cellulolytic, amylolytic and lactic acid-utilising bacteria, respectively.
      Consequently, providing horses with pelleted or steam-flaked instead of ground
      barley forms may limit the negative impact of starch on fibre digestibility in
      horses fed a high level of starch in the morning meal (0.27% BW). Moreover, the
      fibre-to-starch ratio fed in this experiment did not cause any digestive upset. 

PMID- 26316025
TI  - The Mediterranean diet among British older adults: Its understanding,
      acceptability and the feasibility of a randomised brief intervention with two
      levels of dietary advice.
AB  - OBJECTIVES: To assess (i) understanding, acceptability and preference for two
      graphical displays of the Mediterranean diet (MD); and (ii) feasibility of a
      brief MD intervention and cost of adherence to this diet among British older
      adults. DESIGN: Two studies undertaken at the Human Nutrition Research Centre,
      Newcastle University are reported. In study-1, preference and understanding of
      the MD guidelines and two graphical displays, a plate and a pyramid, were
      evaluated in an educational group session (EGS). In study-2, we evaluated the
      feasibility of a three-week brief MD intervention with two levels of dietary
      advice: Group-1 (level 1) attended an EGS on the MD, and Group-2 (level 2)
      attended an EGS and received additional support. MD adherence using a 9-point
      score, and the cost of food intake during intervention, were assessed. RESULTS
      STUDY-1: No differences in preference for a MD plate or pyramid were observed.
      Both graphic displays were rated as acceptable and conveyed clearly these
      guidelines. STUDY-2: The intervention was rated as acceptable. No significant
      differences were observed between groups 1 and 2. Analysis of the combined sample
      showed significant increases from baseline in fish intake (P=0.01) and MD score
      (P=0.05). The cost of food intake during intervention was not significantly
      different from baseline. CONCLUSION: British older adults rated a MD as an
      acceptable model of healthy eating, and a plate and a pyramid as comprehensible
      graphic displays of these guidelines. A brief dietary intervention was also
      acceptable and revealed that greater adherence to the MD could be achieved
      without incurring significantly greater costs.

PMID- 26316027
TI  - 16th International Workshop on Co-morbidities and Adverse Drug Reactions in HIV.

PMID- 26316026
TI  - Effects of handgrip exercise or inorganic nitrate supplementation on 24-h
      ambulatory blood pressure and peripheral arterial function in overweight and
      obese middle age and older adults: A pilot RCT.
AB  - INTRODUCTION: Hypertension is a major contributor to the global burden of
      cardiovascular diseases and its prevalence increases progressively with ageing.
      Therefore the identification of effective, age-friendly exercise and nutritional
      interventions which lower blood pressure (BP) is a research priority. OBJECTIVE:
      To undertake a pilot RCT examining the efficacy of isometric handgrip exercise
      (IHGE) and beetroot juice (a rich source of inorganic nitrate) consumption in
      modifying clinic and 24-h ambulatory BP (24-h ABP), peripheral arterial function
      and plasma asymmetric dimethylarginine (ADMA) in older overweight and obese
      adults. DESIGN: Thirty middle age and older adults (62+/-5 years) were randomised
      to: (a) bilateral IHGE at 50% of maximal voluntary contraction (8 min/day), (b)
      140 ml/day of concentrated beetroot juice, or (c) no-intervention (control
      group), for 7 days. All groups followed a standardised diet to control nitrate
      intake. Clinic and 24-h ABP, peripheral arterial function quantified by pulse
      wave velocity (PWV) and arterial volume distensibility were assessed before and
      after intervention. SETTING: Clinical ageing research unit, Newcastle University.
      RESULTS: At baseline, there were no between-group differences in age, handgrip
      strength, clinic or 24-h ABP, BMI, waist circumference, fat mass, physical
      activity level, energy intake or urinary and plasma nitrate concentrations. After
      intervention, there were no significant effects on clinic systolic and diastolic
      BP or 24-h ABP, PWV (p=0.54), arterial volume distensibility (p=0.89), or ADMA
      (p=0.45). CONCLUSIONS: IHGE or beetroot juice consumption for 7 days did not
      affect BP or peripheral arterial function in overweight and obese middle age and
      older adults. Ageing may reduce the effects of these interventions on vascular
      function and studies are needed to test this hypothesis.

PMID- 26316028
TI  - "It is meaningful; I feel that I can make a difference" -A qualitative study
      about GPs' experiences of work at nursing homes in Sweden.
AB  - + BACKGROUND: Swedish nursing homes (NH) have limited capacity. As a result
      elderly people living in NH represent the part of the elderly population in most
      need of care. In Sweden a General Practitioner (GP) is usually responsible for
      the medical care of all subjects living in a NH. The residents in NH seldom have
      adequate pharmacological treatment according to diagnosis and often have
      polypharmacy and/or inappropriate medical treatment regarding concerns of
      declining renal function. What prevents optimal care for the elderly is
      multifaceted, but there is limited research on how GPs experience their work with
      the elderly in NH in Sweden. This study aims to illuminate the GPs' work with the
      elderly in NH to provide input on how the care can be improved, as well as to
      identify potential obstacles for good quality of care. METHODS: This qualitative
      study is based on individual semi-structured interviews with 12 GPs and a follow
      up focus group discussion with six of the interviewed GPs. The interviews were
      analysed with systematic text condensation, with the process leading to identify
      categories and themes. Thereafter, the themes were discussed among six of the
      participating GPs in a focus group interview. RESULTS: Two main themes were
      identified: concern for the patient and sustainable working conditions. The
      principal focus for the GPs was to contribute to the best possible quality of
      life for the patients. The GPs described discordance between the demand from
      staff for medications and the patients' actual need of care. GPs found their work
      with NH enjoyable. Even though the patients at the NH often suffered from
      multiple illnesses, which could lead to difficult decisions being made, the
      doctors felt confident in their role by having a holistic view of the patient in
      tandem with reliable support from the nurse at the NH. CONCLUSION: Working with
      NH patients was considered important and meaningful, with the GPs striving for
      the patient's well-being with special consideration to the continuum of ageing. A
      continuous and well-functioning relationship between the GP and the nurse was
      crucial for the patients' well-being.

PMID- 26316029
TI  - A Graph-Theoretical Approach for Tracing Filamentary Structures in Neuronal and
      Retinal Images.
AB  - The aim of this study is about tracing filamentary structures in both neuronal
      and retinal images. It is often crucial to identify single neurons in neuronal
      networks, or separate vessel tree structures in retinal blood vessel networks, in
      applications such as drug screening for neurological disorders or computer-aided
      diagnosis of diabetic retinopathy. Both tasks are challenging as the same
      bottleneck issue of filament crossovers is commonly encountered, which
      essentially hinders the ability of existing systems to conduct large-scale drug
      screening or practical clinical usage. To address the filament crossovers'
      problem, a two-step graph-theoretical approach is proposed in this paper. The
      first step focuses on segmenting filamentary pixels out of the background. This
      produces a filament segmentation map used as input for the second step, where
      they are further separated into disjointed filaments. Key to our approach is the
      idea that the problem can be reformulated as label propagation over directed
      graphs, such that the graph is to be partitioned into disjoint sub-graphs, or
      equivalently, each of the neurons (vessel trees) is separated from the rest of
      the neuronal (vessel) network. This enables us to make the interesting connection
      between the tracing problem and the digraph matrix-forest theorem in algebraic
      graph theory for the first time. Empirical experiments on neuronal and retinal
      image datasets demonstrate the superior performance of our approach over existing
      methods. 

PMID- 26316030
TI  - Mobile Biplane X-Ray Imaging System for Measuring 3D Dynamic Joint Motion During
      Overground Gait.
AB  - Most X-ray fluoroscopy systems are stationary and impose restrictions on the
      measurement of dynamic joint motion; for example, knee-joint kinematics during
      gait is usually measured with the subject ambulating on a treadmill. We developed
      a computer-controlled, mobile, biplane, X-ray fluoroscopy system to track human
      body movement for high-speed imaging of 3D joint motion during overground gait. A
      robotic gantry mechanism translates the two X-ray units alongside the subject,
      tracking and imaging the joint of interest as the subject moves. The main aim of
      the present study was to determine the accuracy with which the mobile imaging
      system measures 3D knee-joint kinematics during walking. In vitro experiments
      were performed to measure the relative positions of the tibia and femur in an
      intact human cadaver knee and of the tibial and femoral components of a total
      knee arthroplasty (TKA) implant during simulated overground gait. Accuracy was
      determined by calculating mean, standard deviation and root-mean-squared errors
      from differences between kinematic measurements obtained using volumetric models
      of the bones and TKA components and reference measurements obtained from metal
      beads embedded in the bones. Measurement accuracy was enhanced by the ability to
      track and image the joint concurrently. Maximum root-mean-squared errors were
      0.33 mm and 0.65 degrees  for translations and rotations of the TKA knee and 0.78
      mm and 0.77 degrees  for translations and rotations of the intact knee, which are
      comparable to results reported for treadmill walking using stationary biplane
      systems. System capability for in vivo joint motion measurement was also
      demonstrated for overground gait.

PMID- 26316031
TI  - Hydrolytic and oxidative degradation of electrospun supramolecular biomaterials:
      In vitro degradation pathways.
AB  - The emerging field of in situ tissue engineering (TE) of load bearing tissues
      places high demands on the implanted scaffolds, as these scaffolds should provide
      mechanical stability immediately upon implantation. The new class of synthetic
      supramolecular biomaterial polymers, which contain non-covalent interactions
      between the polymer chains, thereby forming complex 3D structures by self
      assembly. Here, we have aimed to map the degradation characteristics of promising
      (supramolecular) materials, by using a combination of in vitro tests. The
      selected biomaterials were all polycaprolactones (PCLs), either conventional and
      unmodified PCL, or PCL with supramolecular hydrogen bonding moieties (either 2
      ureido-[1H]-pyrimidin-4-one or bis-urea units) incorporated into the backbone. As
      these materials are elastomeric, they are suitable candidates for cardiovascular
      TE applications. Electrospun scaffold strips of these materials were incubated
      with solutions containing enzymes that catalyze hydrolysis, or solutions
      containing oxidative species. At several time points, chemical, morphological,
      and mechanical properties were investigated. It was demonstrated that
      conventional and supramolecular PCL-based polymers respond differently to enzyme
      accelerated hydrolytic or oxidative degradation, depending on the morphological
      and chemical composition of the material. Conventional PCL is more prone to
      hydrolytic enzymatic degradation as compared to the investigated supramolecular
      materials, while, in contrast, the latter materials are more susceptible to
      oxidative degradation. Given the observed degradation pathways of the examined
      materials, we are able to tailor degradation characteristics by combining
      selected PCL backbones with additional supramolecular moieties. The presented
      combination of in vitro test methods can be employed to screen, limit, and select
      biomaterials for pre-clinical in vivo studies targeted to different clinical
      applications. 

PMID- 26316032
TI  - Highly Efficient Enrichment of Volatile Iodine by Charged Porous Aromatic
      Frameworks with Three Sorption Sites.
AB  - The targeted synthesis of a series of novel charged porous aromatic frameworks
      (PAFs) is reported. The compounds PAF-23, PAF-24, and PAF-25 are built up by a
      tetrahedral building unit, lithium tetrakis(4-iodophenyl)borate (LTIPB), and
      different alkyne monomers as linkers by a Sonogashira-Hagihara coupling reaction.
      They possess excellent adsorption properties to organic molecules owing to their
      "breathing" dynamic frameworks. As these PAF materials assemble three effective
      sorption sites, namely the ion bond, phenyl ring, and triple bond together, they
      exhibit high affinity and capacity for iodine molecules. To the best of our
      knowledge, these PAF materials give the highest adsorption values among all
      porous materials (zeolites, metal-organic frameworks, and porous organic
      frameworks) reported to date. 

PMID- 26316033
TI  - Metrics of separation performance in chromatography: Part 3: General separation
      performance of linear solvent strength gradient liquid chromatography.
AB  - The separation performance metrics defined in Part 1 of this series are applied
      to the evaluation of general separation performance of linear solvent strength
      (LSS) gradient LC. Among the evaluated metrics was the peak capacity of an
      arbitrary segment of a chromatogram. Also evaluated were the peak width, the
      separability of two solutes, the utilization of separability, and the speed of
      analysis-all at an arbitrary point of a chromatogram. The means are provided to
      express all these metrics as functions of an arbitrary time during LC analysis,
      as functions of an arbitrary outlet solvent strength changing during the
      analysis, as functions of parameters of the solutes eluting during the analysis,
      and as functions of several other factors. The separation performance of gradient
      LC is compared with the separation performance of temperature-programmed GC
      evaluated in Part 2. 

PMID- 26316034
TI  - Development and validation of a rapid ultra-high performance liquid
      chromatography method for the assay of benzalkonium chloride using a quality-by
      design approach.
AB  - A rapid robust reversed-phase UHPLC method has been developed for the analysis of
      total benzalkonium chloride in preserved drug formulation. A systematic Quality
      by-Design (QbD) method development approach using commercial, off the shelf
      software (Fusion AE((r))) has been used to optimize the column, mobile phases,
      gradient time, and other HPLC conditions. Total benzalkonium chloride analysis
      involves simple sample preparation. The method uses gradient elution from an ACE
      Excel 2 C18-AR column (50mm*2.1mm, 2.0MUm particle size), ammonium phosphate
      buffer (pH 3.3; 10mM) as aqueous mobile phase and methanol/acetonitrile (85/15,
      v/v) as the organic mobile phase with UV detection at 214nm. Using these
      conditions, major homologs of the benzalkonium chloride (C12 and C14) have been
      separated in less than 2.0min. The validation results confirmed that the method
      is precise, accurate and linear at concentrations ranging from 0.025mg/mL to
      0.075mg/mL for total benzalkonium chloride. The recoveries ranged from 99% to
      103% at concentrations from 0.025mg/mL to 0.075mg/mL for total benzalkonium
      chloride. The validation results also confirmed the robustness of the method as
      predicted by Fusion AE((r)). 

PMID- 26316035
TI  - Multidetector thermal field-flow fractionation as a unique tool for the tacticity
      based separation of poly(methyl methacrylate)-polystyrene block copolymer
      micelles.
AB  - Poly(methyl methacrylate)-polystyrene (PMMA-PS) micelles with isotactic and
      syndiotactic coronas are prepared in acetonitrile and subjected to thermal field
      flow fractionation (ThFFF) analysis at various conditions of increasing
      temperature gradients. It is shown for the first time that multidetector ThFFF
      provides comprehensive information on important micelle characteristics such as
      size (Dh), shape (Rg/Rh), aggregation number (Z), thermal diffusion (DT) and
      Soret coefficients (ST) as a function of temperature from a single injection.
      Moreover, it is found that micelles exhibit a unique decreasing trend in DT as a
      function of temperature which is independent of the tacticity of the corona and
      the micelle preparation method used. It is also demonstrated that ThFFF can
      monitor micelle to vesicle transitions as a function of temperature. In addition
      to ThFFF, it is found from DLS analysis that the tacticity of the corona
      influences the critical micelle concentration and the magnitude to which micelles
      expand/contract with temperature. The tacticity does not, however, influence the
      critical micelle temperature. Furthermore, the separation of micelles based on
      the tacticity of the corona highlight the unique capabilities of ThFFF. 

PMID- 26316036
TI  - Do stars govern our actions? Astrocyte involvement in rodent behavior.
AB  - Astrocytes have emerged as important partners of neurons in information
      processing. Important progress has been made in the past two decades in
      understanding the role of astrocytes in the generation of neuron-astrocyte
      network outputs resulting in behavior. We review evidence for astrocyte
      involvement across four different behavioral domains: cognition, emotion, motor,
      and sensory processing. Accumulating evidence from animal models has provided a
      wealth of data that largely supports a direct involvement of astrocytes on
      diverse aspects of behavior. The development of tools for selectively controlling
      the temporal and spatial properties of astrocyte activity will help to
      consolidate our knowledge of the mechanisms underlying this involvement. 

PMID- 26316037
TI  - Engineering the electronic state of a perovskite electrocatalyst for
      synergistically enhanced oxygen evolution reaction.
AB  - A surface hydrogen effect to modulate the pure electronic-state transition in
      perovskite Ca0.9 Yb0.1 MnO3 synergistically generates a more suitable eg electron
      filling status and better conductivity. This achieves 100 times higher catalytic
      activity compared to that of a pristine sample. 

PMID- 26316038
TI  - Ghrelin, neuropeptide Y (NPY) and cholecystokinin (CCK) in blunt snout bream
      (Megalobrama amblycephala): cDNA cloning, tissue distribution and mRNA expression
      changes responding to fasting and refeeding.
AB  - Blunt snout bream (Megalobrama amblycephala Yih, 1955) is an endemic freshwater
      fish in China for which the endocrine mechanism of regulation of feeding has
      never been examined. Ghrelin, neuropeptide Y (NPY) and cholecystokinin (CCK) play
      important roles in the regulation of fish feeding. In this study, full-length
      cDNAs of ghrelin, NPY and CCK were cloned and analyzed from blunt snout bream.
      Both the ghrelin and NPY genes of blunt snout bream had the same amino acid
      sequences as grass carp, and CCK also shared considerable similarity with that of
      grass carp. The three genes were expressed in a wide range of adult tissues, with
      the highest expression levels of ghrelin in the hindgut, NPY in the hypothalamus
      and CCK in the pituitary, respectively. Starvation challenge experiments showed
      that the expression levels of ghrelin and NPY mRNA increased in brain and
      intestine after starvation, and the expression levels of CCK decreased after
      starvation. Refeeding could bring the expression levels of the three genes back
      to the control levels. These results indicated that the feeding behavior of blunt
      snout bream was regulated by the potential correlative actions of ghrelin, NPY
      and CCK, which contributed to the defense against starvation. This study will
      further our understanding of the function of ghrelin, NPY and CCK and the
      molecular mechanism of feeding regulation in teleosts.

PMID- 26316039
TI  - Appetite regulation in Schizothorax prenanti by three CART genes.
AB  - In recent years, cocaine- and amphetamine-regulated transcript (CART) has
      received much attention as mediators of appetite regulation in mammals. However,
      the involvement of CART in the feeding behavior of teleosts has not been well
      understood. In this study, three distinct CARTs were cloned from the Schizothorax
      prenanti (S. prenanti). Real-time quantitative PCR were applied to characterize
      the tissue distribution and appetite regulatory effects of CARTs in S. prenanti.
      The S. prenanti CART-1, CART-2 and CART-3 full-length cDNA sequences were 597 bp,
      694 bp and 749 bp in length, encoding the peptides of 125, 120 and 104 amino acid
      residues, respectively. All the S. prenanti CARTs consisted of three exons and
      two introns. Tissue distribution analysis showed that the high mRNA levels of S.
      prenanti CART-1 were observed in the telencephalon and eye, followed by the
      hypothalamus, myelencephalon, and mesencephalon. The S. prenanti CART-2 mRNA was
      mainly found in the mesencephalon, hypothalamus, telencephalon and
      myelencephalon. The S. prenanti CART-3 mRNA was widely distributed among the
      tissues, with the high levels in the hypothalamus and foregut. In the
      periprandial experiment, all three CARTs mRNA expressions in the hypothalamus
      were highly elevated after a meal, suggesting that CARTs are postprandial satiety
      signals. In the fasting experiment, all three CARTs mRNA expressions decreased
      after fasting and increased after refeeding, suggesting that CARTs might be
      involved in regulation of appetite in the S. prenanti.

PMID- 26316040
TI  - Association of Polymorphisms of Cytochrome P450 2D6 With Blood Hydroxychloroquine
      Levels in Patients With Systemic Lupus Erythematosus.
AB  - OBJECTIVE: To evaluate associations of genetic polymorphisms in cytochrome P450
      (CYP) isoforms 2D6, 3A5, and 3A4 with blood concentrations of hydroxychloroquine
      (HCQ) and its metabolite, N-desethyl HCQ (DHCQ), in patients with systemic lupus
      erythematosus (SLE). METHODS: SLE patients taking HCQ for >3 months were
      recruited and were genotyped for 4 single-nucleotide polymorphisms in CYP2D6*10,
      CYP3A5*3, and CYP3A4*18B. Blood HCQ and DHCQ concentrations ([HCQ] and [DHCQ])
      were measured and their association with corresponding genotypes was
      investigated. RESULTS: A total of 194 patients were included in the analysis.
      CYP2D6*10 polymorphisms (rs1065852 and rs1135840) were significantly associated
      with the [DHCQ]:[HCQ] ratio after adjustment for age, sex, dose per weight per
      day, and SLE Disease Activity Index score (P = 0.03 and P < 0.01, respectively).
      In adjusted models, the [DHCQ]:[HCQ] ratio was highest in patients with the G/G
      genotype of the CYP2D6*10 (rs1065852) polymorphism and lowest in those with the
      A/A genotype (P = 0.03). Similarly, the [DHCQ]:[HCQ] ratio was highest in
      patients with the C/C genotype of the CYP2D6*10 (rs1135840) polymorphism and
      lowest in those with the G/G genotype (P < 0.01). The CYP2D6*10 (rs1065852)
      polymorphism was significantly related to the [DHCQ] (P = 0.01). However, the
      polymorphisms of CYP3A5*3 and CYP3A4*18B did not show any significant association
      with the [HCQ], [DHCQ], or [DHCQ]:[HCQ] ratio. CONCLUSION: Our study showed that
      the [DHCQ]:[HCQ] ratio was related to CYP2D6 polymorphisms in Korean lupus
      patients taking oral HCQ. CYP polymorphisms may explain why there is wide
      variation in blood HCQ concentrations. The role of an individual's CYP
      polymorphisms should be considered when prescribing oral HCQ.

PMID- 26316041
TI  - E-cadherin knockdown increases beta-catenin reducing colorectal cancer
      chemosensitivity only in three-dimensional cultures.
AB  - Decreased expression of E-cadherin correlates with poor prognosis in colorectal
      cancer. Certain E-cadherin signaling cascades are triggered by intercellular
      force or binding to cadherins on adjacent cells. Three-dimensional (3D) cell
      cultures represent a better approximation of cell-cell adhesion in vivo than two
      dimensional (2D) cultures. Here, we explored the role of E-cadherin in colorectal
      cancer chemosensitivity in 3D cultures. Cell-cell junctions, including tight
      junctions, gap junctions, intermediate junctions and desmosomes, were commonly
      found in 3D cultures. Knockdown of E-cadherin by lentiviral delivery of shRNA
      significantly reduced chemosensitivity to 5-fluorouracil and irinotecan,
      increased beta-catenin protein level in HCT116 3D cultures. However, these
      effects were not observed in 2D cultures. Knockdown of beta-catenin significantly
      increased chemosensitivity to 5-fluorouracil and irinotecan in HCT116 3D cultures
      and LoVo 3D cultures. 5-Fluorouracil activated p38, ERK1/2 and JNK1/2 in a time
      dependent manner in HCT116 3D cultures. E-cadherin knockdown enhanced p-p38 and p
      ERK1/2, except p-JNK1/2 in HCT116 3D cultures. Knockdown of beta-catenin
      attenuated p-p38 and p-ERK1/2 in HCT116 3D cultures and LoVo 3D cultures.
      Inhibition of p-p38 or p-ERK1/2 in HCT116 3D cultures significantly increased
      chemosensitivity. Our results indicate E-cadherin knockdown increases beta
      catenin resulting in reduction of chemosensitivity only in 3D cultures, and beta
      catenin increasing the p-p38/p-ERK1/2 is involved in this mechanism.

PMID- 26316042
TI  - Role of Fatty Acid-Binding Protein 2 Ala54Thr Genotype on Weight Loss and
      Cardiovascular Risk Factors after a High-Protein/Low-Carbohydrate versus a
      Standard Hypocaloric Diet during 9 Months.
AB  - BACKGROUND: It has been found that the expression of fatty acid-binding protein 2
      gene mRNA is under dietary control. The polymorphism Ala54Thr of this protein was
      associated with high insulin resistance. OBJECTIVE: The aim of our study was to
      investigate the influence of Thr54 polymorphism on metabolic response, weight
      loss and serum adipokine levels secondary to high-protein/low-carbohydrate vs.
      standard hypocaloric diets during 9 months. DESIGN: A population of 193 obese
      subjects was analyzed in a randomized trial. A nutritional evaluation was
      performed at the beginning and at the end of a 9-month period in which subjects
      received 1 of 2 diets (diet HP: high-protein/low-carbohydrate vs. diet S:
      standard diet). RESULTS: With both diets and in both genotype groups, body mass
      index, weight, fat mass, waist circumference, systolic blood pressure and leptin
      levels decreased. With both diets and only in wild genotype (diet HP vs. diet S),
      glucose (-6.2 +/- 2.1 vs. -4.9 +/- 2.0 mg/dl; p < 0.05), insulin levels (-5.0 +/-
      3.9 vs. -2.0 +/- 2.1 UI/l; p < 0.05), homeostasis model assessment for insulin
      resistance (HOMA-R) (-1.1 +/- 0.9 vs. -0.7 +/- 1.0 units; p < 0.05) decreased.
      The improvement in these parameters was higher with diet HP than HS. With both
      diets and only in the wild genotype, total cholesterol and LDL-total cholesterol
      levels decreased. CONCLUSION: Carriers of Thr54 allele have a different metabolic
      response after weight loss than wild type non-A carriers obese, with a lack of
      decrease of LDL-cholesterol, glucose, insulin levels and HOMA-R.

PMID- 26316043
TI  - International Veterinary Epilepsy Task Force consensus reports on epilepsy
      definition, classification and terminology, affected dog breeds, diagnosis,
      treatment, outcome measures of therapeutic trials, neuroimaging and
      neuropathology in companion animals.

PMID- 26316044
TI  - Analysis of thin baked-on silicone layers by FTIR and 3D-Laser Scanning
      Microscopy.
AB  - Pre-filled syringes (PFS) and auto-injection devices with cartridges are
      increasingly used for parenteral administration. To assure functionality,
      silicone oil is applied to the inner surface of the glass barrel. Silicone oil
      migration into the product can be minimized by applying a thin but sufficient
      layer of silicone oil emulsion followed by thermal bake-on versus spraying-on
      silicone oil. Silicone layers thicker than 100nm resulting from regular spray-on
      siliconization can be characterized using interferometric profilometers. However,
      the analysis of thin silicone layers generated by bake-on siliconization is more
      challenging. In this paper, we have evaluated Fourier transform infrared (FTIR)
      spectroscopy after solvent extraction and a new 3D-Laser Scanning Microscopy (3D
      LSM) to overcome this challenge. A multi-step solvent extraction and subsequent
      FTIR spectroscopy enabled to quantify baked-on silicone levels as low as 21
      325MUg per 5mL cartridge. 3D-LSM was successfully established to visualize and
      measure baked-on silicone layers as thin as 10nm. 3D-LSM was additionally used to
      analyze the silicone oil distribution within cartridges at such low levels. Both
      methods provided new, highly valuable insights to characterize the siliconization
      after processing, in order to achieve functionality. 

PMID- 26316046
TI  - The role of ambulatory urodynamics in investigation of female urinary
      incontinence.
AB  - INTRODUCTION AND HYPOTHESIS: Lower urinary tract symptoms (LUTS) impact upon
      quality of life and occur in women of all ages. The National Institute for
      Clinical Excellence states that ambulatory urodynamic monitoring (AUM) should be
      used as a second-line investigational modality; however, its use is becoming more
      frequent. AUM provides a valid second line to conventional urodynamic methods
      that may be more widely used. METHOD: A literature review was undertaken to
      assess evidence for the use of AUM alongside a retrospective review of patients
      undergoing AUM at a tertiary care centre and symptom reporting at a follow-up
      visit. Both these methods included evidence for pathology detection, technical
      ease of use, recreation of symptoms and patient experience, allowing comparison
      of literature results to those experienced in day-to-day use. RESULTS: The
      literature shows AUM to have sensitivity superior to that of other urodynamic
      investigations. However, evidence suggests this correlates less well with
      clinical effectiveness. Patients felt AUM was superior in recreating their
      symptoms, and they tolerated the procedure well. The increased technical demands
      of AUMs, however, meant that traces were more commonly harder to interpret than
      with conventional urodynamics. Our experience correlates well with the existing
      literature, suggesting increased symptom diagnosis; 63.2 % of diagnoses
      correlated well with symptoms. CONCLUSION: AUM remains an important urodynamic
      method to supplement conventional urodynamics. Evidence suggests it is superior
      in LUTS diagnosis, but its technical difficulty can affect results.

PMID- 26316045
TI  - Cardiovascular status after Kawasaki disease in the UK.
AB  - OBJECTIVE: Kawasaki disease (KD) is an acute vasculitis that causes coronary
      artery aneurysms (CAA) in young children. Previous studies have emphasised poor
      long-term outcomes for those with severe CAA. Little is known about the fate of
      those without CAA or patients with regressed CAA. We aimed to study long-term
      cardiovascular status after KD by examining the relationship between coronary
      artery (CA) status, endothelial injury, systemic inflammatory markers,
      cardiovascular risk factors (CRF), pulse-wave velocity (PWV) and carotid intima
      media thickness (cIMT) after KD. METHODS: Circulating endothelial cells (CECs),
      endothelial microparticles (EMPs), soluble cell-adhesion molecules cytokines,
      CRF, PWV and cIMT were compared between patients with KD and healthy controls
      (HC). CA status of the patients with KD was classified as CAA present (CAA+) or
      absent (CAA-) according to their worst-ever CA status. Data are median (range).
      RESULTS: Ninety-two KD subjects were studied, aged 11.9 years (4.3-32.2), 8.3
      years (1.0-30.7) from KD diagnosis. 54 (59%) were CAA-, and 38 (41%) were CAA+.
      There were 51 demographically similar HC. Patients with KD had higher CECs than
      HC (p=0.00003), most evident in the CAA+ group (p=0.00009), but also higher in
      the CAA- group than HC (p=0.0010). Patients with persistent CAA had the highest
      CECs, but even those with regressed CAA had higher CECs than HC (p=0.011). CD105
      EMPs were also higher in the KD group versus HC (p=0.04), particularly in the
      CAA+ group (p=0.02), with similar findings for soluble vascular cell adhesion
      molecule 1 and soluble intercellular adhesion molecule 1. There was no difference
      in PWV, cIMT, CRF or in markers of systemic inflammation in the patients with KD
      (CAA+ or CAA-) compared with HC. CONCLUSIONS: Markers of endothelial injury
      persist for years after KD, including in a subset of patients without CAA.

PMID- 26316047
TI  - Reference values for ultrasonograpy of peripheral nerves.
AB  - INTRODUCTION: High-resolution ultrasonography (HRU) is a novel method that
      provides morphological information about peripheral nerves. We aimed to determine
      reference values for nerve cross-sectional area (CSA) on HRU. METHODS: One
      hundred healthy volunteers had HRU of median, radial, ulnar, fibular, tibial,
      sural, and superficial fibular nerves at defined sites. The CSA was measured and
      the effects of age, gender, and body mass index (BMI) were evaluated. RESULTS:
      CSA values in healthy subjects are described. CSA is larger in lower limb motor
      nerves than in sensory nerves at similar sites, and the CSA tends to be
      symmetrical. The strongest effect on CSA was for age, although gender and BMI had
      some effects. CONCLUSIONS: This study provides normative values for HRU, and it
      suggests that further research with age- and gender-specific distributions must
      be a key priority in the development of HRU for use as a diagnostic test for
      peripheral nerve diseases.

PMID- 26316049
TI  - A global full-dimensional potential energy surface and quasiclassical trajectory
      study of the O((1)D) + CH4 multichannel reaction.
AB  - We report a new global, full-dimensional ground-state potential energy surface
      (PES) of the O((1)D) + CH4 multichannel reaction, based on high-level ab initio
      calculations and fitting procedures. The PES is a permutationally invariant fit
      to roughly 340 000 electronic energies calculated by the MRCI + Q/aug-cc-pVTZ
      level of theory. Extensive quasiclassical trajectory calculations were carried
      out on the new PES at the collision energy of relevance to the previously
      universal crossed molecular beam experiments. The product branching ratios,
      translational energy distributions and angular distributions of OH + CH3, H +
      CH2OH/CH3O and H2 + HCOH/H2CO product channels were calculated and compared with
      the available experimental results. Very good agreement between theory and
      experiment has been achieved. The O((1)D) + CH4 reaction mainly proceeds through
      the CH3OH intermediate via a trapped abstraction mechanism, starting with the
      abstraction of the hydrogen atom, rather than the direct insertion pathway with
      the O((1)D) atom directly inserting into the C-H bond of CH4. The process with a
      very short lifetime behaves like an abstraction reaction, producing a pronounced
      forward scattering peak as found in the OH + CH3 channel, while the process with
      a relatively long lifetime produces reaction products with nearly forward and
      backward scattering symmetry, similar to an insertion reaction, as found in other
      reaction channels. 

PMID- 26316048
TI  - Down-regulation of BDNF in cell and animal models increases striatal-enriched
      protein tyrosine phosphatase 61 (STEP61 ) levels.
AB  - Brain-derived neurotrophic factor (BDNF) regulates synaptic strengthening and
      memory consolidation, and altered BDNF expression is implicated in a number of
      neuropsychiatric and neurodegenerative disorders. BDNF potentiates N-methyl-D
      aspartate receptor function through activation of Fyn and ERK1/2. STriatal
      Enriched protein tyrosine Phosphatase (STEP) is also implicated in many of the
      same disorders as BDNF but, in contrast to BDNF, STEP opposes the development of
      synaptic strengthening. STEP-mediated dephosphorylation of the NMDA receptor
      subunit GluN2B promotes internalization of GluN2B-containing NMDA receptors,
      while dephosphorylation of the kinases Fyn, Pyk2, and ERK1/2 leads to their
      inactivation. Thus, STEP and BDNF have opposing functions. In this study, we
      demonstrate that manipulation of BDNF expression has a reciprocal effect on
      STEP61 levels. Reduced BDNF signaling leads to elevation of STEP61 both in
      BDNF(+/-) mice and after acute BDNF knockdown in cortical cultures. Moreover, a
      newly identified STEP inhibitor reverses the biochemical and motor abnormalities
      in BDNF(+/-) mice. In contrast, increased BDNF signaling upon treatment with a
      tropomyosin receptor kinase B agonist results in degradation of STEP61 and a
      subsequent increase in the tyrosine phosphorylation of STEP substrates in
      cultured neurons and in mouse frontal cortex. These findings indicate that BDNF
      tropomyosin receptor kinase B signaling leads to degradation of STEP61 , while
      decreased BDNF expression results in increased STEP61 activity. A better
      understanding of the opposing interaction between STEP and BDNF in normal
      cognitive functions and in neuropsychiatric disorders will hopefully lead to
      better therapeutic strategies. Altered expression of BDNF and STEP61 has been
      implicated in several neurological disorders. BDNF and STEP61 are known to
      regulate synaptic strengthening, but in opposite directions. Here, we report that
      reduced BDNF signaling leads to elevation of STEP61 both in BDNF(+/-) mice and
      after acute BDNF knockdown in cortical cultures. In contrast, activation of TrkB
      receptor results in the degradation of STEP61 and reverses hyperlocomotor
      activity in BDNF(+/-) mice. Moreover, inhibition of STEP61 by TC-2153 is
      sufficient to enhance the Tyr phosphorylation of STEP substrates and also
      reverses hyperlocomotion in BDNF(+/-) mice. These findings give us a better
      understanding of the regulation of STEP61 by BDNF in normal cognitive functions
      and in neuropsychiatric disorders. 

PMID- 26316051
TI  - Triad of Intraspinal Meningioma, Schwannoma, and Ependymoma: Report of an
      Extremely Rare Case.
AB  - Mixed tumors composed of schwannoma and meningioma are extremely rare and are
      usually associated with neurofibromatosis type 2. So far, all the cases reported
      have involved the cerebellopontine angle. Only 3 reported cases did not have a
      clear association with neurofibromatosis type 2. We report a mixed tumor
      comprising schwannoma admixed with meningioma and ependymoma in the cervical
      spinal cord of a 22-year-old male. 

PMID- 26316052
TI  - Thyroid Transcription Factor-1 Expression in Adenocarcinomas of the Bile Duct.
AB  - BACKGROUND: The immunoreactivity of thyroid transcription factor-1 (TTF-1) is a
      very specific marker for lung and thyroid neoplasms; the expression of TTF-1 has
      also been demonstrated in extrapulmonary carcinomas. We examined the expression
      of TTF-1 in 15 intestinal-type adenocarcinomas of the extrahepatic bile duct. We
      then compared the expression to TTF-1 staining with other immunohistochemical
      markers including cytokeratin (CK) 7, CK20, caudal-type homeobox transcription
      factor 2 (CDX2), Napsin A, and MUC2. We additionally compared the
      clinicopathological prognostic factors with the TTF-1 expression status. RESULTS:
      Nuclear TTF-1 staining was detected in 2 cases (13.3%), and Napsin A was positive
      in the same 2 cases (13.3%). All cases were positive for CK20, CDX2, and MUC2; 5
      cases were positive for CK7. There was no correlation between TTF-1 expression
      and the clinicopathological characteristics. CONCLUSIONS: To avoid potential
      pitfalls, TTF-1 should be interpreted in conjunction with the clinical setting,
      histology, and the results of markers such as CK7, CK20, Napsin A, and CDX2. This
      report is the first of TTF-1 positivity in adenocarcinomas from the extrahepatic
      biliary tract.

PMID- 26316050
TI  - Prevascularized silicon membranes for the enhancement of transport to implanted
      medical devices.
AB  - Recent advances in drug delivery and sensing devices for in situ applications are
      limited by the diffusion-limiting foreign body response of fibrous encapsulation.
      In this study, we fabricated prevascularized synthetic device ports to help
      mitigate this limitation. Membranes with rectilinear arrays of square pores with
      widths ranging from 40 to 200 MUm were created using materials (50 MUm thick
      double-sided polished silicon) and processes (photolithography and directed
      reactive ion etching) common in the manufacturing of microfabricated sensors.
      Vascular endothelial cells responded to membrane geometry by either forming
      vascular tubes that extended through the pore or completely filling membrane
      pores after 4 days in culture. Although tube formation began to predominate
      overgrowth around 75 MUm and continued to increase at even larger pore sizes,
      tubes formed at these large pore sizes were not completely round and had
      relatively thin walls. Thus, the optimum range of pore size for
      prevascularization of these membranes was estimated to be 75-100 MUm. This study
      lays the foundation for creating a prevascularized port that can be used to
      reduce fibrous encapsulation and thus enhance diffusion to implanted medical
      devices and sensors. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B:
      Appl Biomater, 104B: 1602-1609, 2016.

PMID- 26316053
TI  - Surgeon performed ultrasound-guided fine-needle aspirates of the thyroid: 1067
      biopsies and learning curve in a teaching center.
AB  - BACKGROUND: Surgeon performed ultrasound-guided fine-needle aspirates (UG-FNAs)
      reduce delay in diagnosis and allow for surgeon surveillance. We present the
      first report on a learning curve and impact of head and neck surgical trainees on
      adequacy rates. METHODS: Thyroid UG-FNA biopsies from 2009 to 2013 were reviewed
      retrospectively. Specimen adequacy, cytologic diagnosis, and surgical pathology
      were used to calculate adequacy and accuracy. RESULTS: One thousand sixty-seven
      biopsies were examined in 723 individuals. The adequacy rate from adoption into
      practice improved from 71% to 78% to 85% over 300 cases. When UG-FNA was
      subsequently taught to trainees, adequacy rates varied among trainees (p < .037),
      and there were higher nondiagnostic rates earlier in training (p = .04). Adequacy
      was not related to size or palpability, but cystic lesions yielded more
      inadequate specimens (p < .001). CONCLUSION: Surgeon performed UG-FNA biopsy can
      be performed adequately in an outpatient setting. Adequacy rates reach acceptable
      levels after 300 cases, whereas trainee involvement impacts adequacy rates. (c)
      2015 Wiley Periodicals, Inc. Head Neck 38: E1281-E1284, 2016.

PMID- 26316055
TI  - Erratum.

PMID- 26316054
TI  - Safety Profile of Certolizumab Pegol in Patients with Immune-Mediated
      Inflammatory Diseases: A Systematic Review and Meta-Analysis.
AB  - INTRODUCTION: Certolizumab pegol (CZP), an anti-tumor necrosis factor PEGylated
      Fab' fragment of a humanized monoclonal antibody, is currently approved for
      treatment of some immune-mediated inflammatory diseases (IMIDs). To our
      knowledge, no systematic review and meta-analysis evaluating the overall safety
      profile of CZP has been performed. OBJECTIVE: The objective of this systematic
      review was to assess the adverse event (AE) patterns of CZP versus a control in
      patients with IMIDs. METHODS: A systematic literature search was performed using
      PubMed/MEDLINE, EMBASE, the Cochrane Library, and the FDA database for clinical
      trials up to March 2014. Eligible studies were those that compared the safety
      profile of CZP to a control group in patients with IMIDs. The following data were
      extracted: number of patients experiencing AEs, serious AEs (SAEs), adverse drug
      reactions (ADRs), withdrawals due to AEs, fatal AEs, infectious AEs and SAEs,
      upper respiratory tract infections, injection-site reactions, neoplasms, and
      tuberculosis. RESULTS: A total of 2023 references were identified and 18
      randomized controlled trials were included. The main pooled risk ratios of CZP
      treated versus control patients were as follows: AEs 1.09 (95% confidence
      interval, CI 1.04-1.14), SAEs 1.50 (95% CI 1.21-1.86), ADRs 1.20 (95% CI 1.03
      1.39), infectious AEs 1.28 (95% CI 1.13-1.45), infectious SAEs 2.17 (95% CI 1.36
      3.47), and upper respiratory tract infections 1.34 (95% CI 1.15-1.57).
      CONCLUSION: Safety data on CZP suggest an overall favorable tolerability profile,
      with infections being the most common AE. However, CZP-treated patients had a
      twofold higher risk of infectious SAEs than control patients. Large observational
      studies and data from national registries are needed to detect rare AEs, which
      might occur after long-term exposures to CZP.

PMID- 26316056
TI  - Delayed reactivation of chronic infantile neurologic, cutaneous, articular
      syndrome (CINCA) in a patient with somatic mosaicism of CIAS1/NLRP3 gene after
      withdrawal of anti-IL-1 beta therapy.

PMID- 26316057
TI  - Neurochemical factors underlying individual differences in locomotor activity and
      anxiety-like behavioral responses in zebrafish.
AB  - Variation among individuals may arise for several reasons, and may have diverse
      underlying mechanisms. Individual differences have been studied in a variety of
      species, but recently a new model organism has emerged in this field that offers
      both sophistication in phenotypical characterization and powerful mechanistic
      analysis. Recently, zebrafish, one of the favorites of geneticists, have been
      shown to exhibit consistent individual differences in baseline locomotor
      activity. In the current study, we further explore this finding and examine
      whether individual differences in locomotor activity correlate with anxiety-like
      behavioral measures and with levels of dopamine, serotonin and the metabolites of
      these neurotransmitters. In addition, we examine whether individual differences
      in locomotor activity are also associated with reactivity to the locomotor
      stimulant effects of and neurochemical responses to acute ethanol exposure (30min
      long, 1% v/v ethanol bath application). Principal component analyses revealed a
      strong association among anxiety-like responses, locomotor activity, serotonin
      and dopamine levels. Furthermore, ethanol exposure was found to abolish the
      locomotion-dependent anxiety-like behavioral and serotonergic responses
      suggesting that this drug also engages a common underlying pathway. Overall, our
      results provide support for an important role of the serotonergic system in
      mediating individual differences in anxiety-like responses and locomotor activity
      in zebrafish and for a minor modulatory role of the dopaminergic system. 

PMID- 26316058
TI  - Intestinal solubility and absorption of poorly water soluble compounds:
      predictions, challenges and solutions.
AB  - We have explored for which type of compounds biorelevant dissolution profiling in
      simulated intestinal fluids would accurately predict solubility in human
      intestinal fluid. In total, 474 solubility values in simulated and aspirated
      human intestinal fluid for 78 drugs were compiled and analyzed. Significant
      solubilization in the colloidal structures was obtained in fasted and fed state
      fluids for drug compounds with a logD(oct)>3. Highly lipophilic compounds with
      high melting points (Tm > 200  degrees C) could also be significantly
      solubilized, but typically such compounds had solubility values in the lower
      ug/ml range also in the presence of the colloidal structures. On the basis of our
      analysis, compounds with a logD(oct)>3 should be explored in biorelevant
      dissolution media to better predict in vivo performance after oral dosing.

PMID- 26316059
TI  - Stigma in youth with Tourette's syndrome: a systematic review and synthesis.
AB  - Tourette's syndrome (TS) is a childhood onset neurodevelopmental disorder,
      characterised by tics. To our knowledge, no systematic reviews exist which focus
      on examining the body of literature on stigma in association with children and
      adolescents with TS. The aim of the article is to provide a review of the
      existing research on (1) social stigma in relation to children and adolescents
      with TS, (2) self-stigma and (3) courtesy stigma in family members of youth with
      TS. Three electronic databases were searched: PsycINFO, PubMed and Web of
      Science. Seventeen empirical studies met the inclusion criteria. In relation to
      social stigma in rating their own beliefs and behavioural intentions, youth who
      did not have TS showed an unfavourable attitude towards individuals with TS in
      comparison to typically developing peers. Meanwhile, in their own narratives
      about their lives, young people with TS themselves described some form of
      devaluation from others as a response to their disorder. Self-degrading comments
      were denoted in a number of studies in which the children pointed out
      stereotypical views that they had adopted about themselves. Finally, as regards
      courtesy stigma, parents expressed guilt in relation to their children's
      condition and social alienation as a result of the disorder. Surprisingly,
      however, there is not one study that focuses primarily on stigma in relation to
      TS and further studies that examine the subject from the perspective of both the
      'stigmatiser' and the recipient of stigma are warranted. 

PMID- 26316060
TI  - App use, physical activity and healthy lifestyle: a cross sectional study.
AB  - BACKGROUND: Physical inactivity is a growing public health concern. Use of mobile
      applications (apps) may be a powerful tool to encourage physical activity and a
      healthy lifestyle. For instance, apps may be used in the preparation of a running
      event. However, there is little evidence for the relationship between app use and
      change in physical activity and health in recreational runners. The aim of this
      study was to determine the relationship between the use of apps and changes in
      physical activity, health and lifestyle behaviour, and self-image of short and
      long distance runners. METHODS: A cross sectional study was designed. A random
      selection of 15,000 runners (of 54,000 participants) of a 16 and 6.4 km
      recreational run (Dam tot Damloop) in the Netherlands was invited to participate
      in an online survey two days after the run. Anthropometrics, app use, activity
      level, preparation for running event, running physical activity (RPA), health and
      lifestyle, and self-image were addressed. A chi-squared test was conducted to
      analyse differences between app users and non-app users in baseline
      characteristics as well as in RPA, healthy lifestyle and perceived health. In
      addition, a multivariate logistic regression analysis was performed to determine
      if app use could predict RPA, perceived health and lifestyle, and self-image.
      RESULTS: Of the 15,000 invited runners, 28% responded. For both distances, app
      use was positively related to RPA and feeling healthier (p < 0.05). Also, app use
      was positively related to feeling better about themselves, feeling like an
      athlete, motivating others to participate in running, and losing weight (p <
      0.01). Furthermore, for 16 km runners app use was positively related to eating
      healthier, feeling more energetic and reporting a higher chance to maintain sport
      behaviour (p < 0.05). CONCLUSIONS: These results suggest that use of mobile apps
      has a beneficial role in the preparation of a running event, as it promotes
      health and physical activity. Further research is now needed to determine a
      causal relationship between app use and physical and health related behaviour.

PMID- 26316061
TI  - Agreement in assessment of infliximab and adalimumab levels in rheumatoid
      arthritis: interlaboratory and interassay comparison.
AB  - OBJECTIVES: Infliximab (IFX) and adalimumab (ADL) drug levels and anti-drug
      antibodies (ADA) are assessed using a variety of techniques, therefore, results
      cannot accurately be compared for clinical purposes. The aim of this study was to
      test two infliximab (IFX) and adalimumab (ADL) ELISA versions, for drug levels
      and ADA, to see whether they yield similar results. METHODS: ELISA versions
      [Promonitor(r) IFX R1 and R2 (V.1), Promonitor(r) IFX and Anti-IFX (V.2);
      Promonitor(r) ADL R1 and R2 (V.1), Promonitor(r) ADL and Anti-ADL (V.2) kits
      (Progenika Biopharma, Spain)] were used to measure drug levels and ADA in IFX
      (n=24) and ADL (n=24) rheumatoid arthritis-treated patients in three independent
      laboratories. Quantitative and qualitative agreements were evaluated using
      intraclass correlation coefficients (ICC), and Cohen's Kappa (kappa)
      respectively. The Bland-Altman plots assessed differences between V.1 and V.2.
      RESULTS: Interlaboratory agreement (ICC/kappa) with V.1 was poor for IFX
      (0.66/0.62) and ADL (0.69/0.52) drug levels; meanwhile, high agreement was found
      with V.2 for IFX (0.98/0.95) and ADL (0.094/1.00). Comparison between V.1 and V.2
      in each laboratory resulted in systematically higher values in V.2 than in V.1
      and poor agreement (ICC/kappa ranges) for IFX (0.12-0.7/ 0.19-0.42) and ADL (0.69
      0.89 /0.50-0.73). CONCLUSIONS: Qualitative measurements result in better
      agreement, as evidenced in our study. Greater agreement in V.2 compared with V.1
      for IFX and ADL levels could be due to a better tune up. Further studies are
      required to standardise methods to establish therapeutic reference ranges.

PMID- 26316062
TI  - Endometrial side population cells: potential adult stem/progenitor cells in
      endometrium.
AB  - Uterine endometrium is one of the most important organs for species preservation.
      However, the physiology of human endometrium remains poorly understood, because
      the human endometrium undergoes rapid and large changes during each menstrual
      cycle and it is very difficult to investigate human endometrium as one organ.
      This remarkable regenerative capacity of human endometrium strongly suggests the
      existence of adult stem cells, and physiology of endometrium cannot be explained
      without adult stem cells. Therefore, investigating endometrial stem/progenitor
      cells should lead to a breakthrough in understanding the normal endometrial
      physiology and the pathophysiology of endometrial neoplastic disorders, such as
      endometriosis and endometrial cancer. Several cell populations have been
      discovered as putative endometrial stem/progenitor cells. Emerging evidence
      reveals that the endometrial side population (SP) is one of the potential
      endometrial stem/progenitor populations. Of all the endometrial stem/progenitor
      cell candidates, the endometrial SP (ESP) is best investigated in vitro and in
      vivo, and has the largest number of references. In this review, we provide an
      overview of the accumulating evidence for the ESP cells, both directly from human
      endometria and from cultured endometrial cells. Furthermore, SP cells are
      compared to other potential stem/progenitor cells, and we discuss their stem cell
      properties. We also discuss the difficulties and unsolved issues in endometrial
      stem cell biology. 

PMID- 26316064
TI  - L-carnitine and pyruvate are prosurvival factors during the storage of stallion
      spermatozoa at room temperature.
AB  - The spermatozoa of many stallions do not tolerate being cooled, restricting the
      commercial viability of these animals and necessitating the development of a
      chemically defined room temperature (RT) storage medium. This study examined the
      impact of two major modulators of oxidative phosphorylation, pyruvate (Pyr) and L
      carnitine (L-C), on the storage of stallion spermatozoa at RT. Optimal
      concentrations of Pyr (10 mM) and L-C (50 mM) were first identified and these
      concentrations were then used to investigate the effects of these compounds on
      sperm functionality and oxidative stress at RT. Mitochondrial and cytosolic
      reactive oxygen species, along with lipid peroxidation, were all significantly
      suppressed by the addition of L-C (48 h MitoSOX Red negative: 46.2% vs. 26.1%; 48
      and 72 h dihydroethidium negative: 61.6% vs. 43.1% and 64.4% vs. 46.9%,
      respectively; 48 and 72 h 4-hydroxynonenal negative: 37.1% vs. 23.8% and 41.6%
      vs. 25.7%, respectively), while the Pyr + L-C combination resulted in
      significantly higher motility compared to the control at 72 h (total motility:
      64.2% vs. 39.4%; progressive motility: 34.2% vs. 15.2%). In addition,
      supplementation with L-C significantly reduced oxidative DNA damage at 72 h (9.0%
      vs. 15.6%). To investigate the effects of L-C as an osmolyte, comparisons were
      made between media that were osmotically balanced with NaCl, choline chloride, or
      L-C. This analysis demonstrated that spermatozoa stored in the L-C balanced
      medium had significantly higher total motility (55.0% vs. 39.0%), rapid motility
      (44.0% vs. 25.7%), and ATP levels (70.9 vs. 12.8 ng/ml) following storage
      compared with the NaCl treatment, while choline chloride did not significantly
      improve these parameters compared to the control. Finally, mass spectrometry was
      used to demonstrate that a combination of Pyr and L-C produced significantly
      higher acetyl-L-carnitine production than any other treatment (6.7 pg/10(6)
      spermatozoa vs. control at 4.0 pg/10(6) spermatozoa). These findings suggest that
      Pyr and L-C could form the basis of a novel, effective RT storage medium for
      equine spermatozoa. 

PMID- 26316063
TI  - In utero exposure to di-(2-ethylhexyl) phthalate induces testicular effects in
      neonatal rats that are antagonized by genistein cotreatment.
AB  - Fetal exposure to endocrine disruptors (EDs) is believed to predispose males to
      reproductive abnormalities. Although males are exposed to combinations of
      chemicals, few studies have evaluated the effects of ED mixtures at
      environmentally relevant doses. Our previous work showed that fetal exposure to a
      mixture of the phytoestrogen genistein (GEN) and the plasticizer di-(2
      ethylhexyl) phthalate (DEHP) induced unique alterations in adult testis. In this
      follow-up study, we examined Postnatal Day 3 (PND3) and PND6 male offspring
      exposed from Gestational Day 14 to parturition to corn oil, 10mg/kg GEN, DEHP, or
      their combination, to gain insight into the early molecular events driving long
      term alterations. DEHP stimulated the mRNA and protein expression of the
      steroidogenic enzyme HSD3B, uniquely at PND3. DEHP also increased the mRNA
      expression of Nestin, a Leydig progenitor/Sertoli cell marker, and markers of
      Sertoli cell (Wt1), gonocyte (Plzf, Foxo1), and proliferation (Pcna) at PND3,
      while these genes were unchanged by the mixture. Redox (Nqo1, Sod2, Sod3, Trx,
      Gst, Cat) and xenobiotic transporter (Abcb1b, Abcg2) gene expression was also
      increased by DEHP at PND3, while attenuated when combined with GEN, suggesting
      the involvement of cellular stress in short-term DEHP effects and a protective
      effect of GEN. The direct effects of GEN and mono-(2-ethylhexyl) phthalate, the
      principal bioactive metabolite of DEHP, on testis were investigated in PND3 organ
      cultures, showing a stimulatory effect of 10 MUM mono-(2-ethylhexyl) phthalate on
      basal testosterone production that was normalized by GEN. These effects
      contrasted with previous reports of androgen suppression and decreased gene
      expression in perinatal rat testis by high DEHP doses, implying that neonatal
      effects are not predictive of adult effects. We propose that GEN, through an
      antioxidant action, normalizes reactive oxygen species-induced neonatal effects
      of DEHP. The notion that these EDs do not follow classical dose-response effects
      and involve different mechanisms of toxicity from perinatal ages to adulthood
      highlights the importance of assessing impacts across a range of doses and ages. 

PMID- 26316065
TI  - Intra-operative adjustment of standard planes in C-arm CT image data.
AB  - PURPOSE: With the help of an intra-operative mobile C-arm CT, medical
      interventions can be verified and corrected, avoiding the need for a post
      operative CT and a second intervention. An exact adjustment of standard plane
      positions is necessary for the best possible assessment of the anatomical regions
      of interest but the mobility of the C-arm causes the need for a time-consuming
      manual adjustment. In this article, we present an automatic plane adjustment at
      the example of calcaneal fractures. METHODS: We developed two feature detection
      methods (2D and pseudo-3D) based on SURF key points and also transferred the SURF
      approach to 3D. Combined with an atlas-based registration, our algorithm adjusts
      the standard planes of the calcaneal C-arm images automatically. The robustness
      of the algorithms is evaluated using a clinical data set. Additionally, we tested
      the algorithm's performance for two registration approaches, two resolutions of C
      arm images and two methods for metal artifact reduction. RESULTS: For the feature
      extraction, the novel 3D-SURF approach performs best. As expected, a higher
      resolution ([Formula: see text] voxel) leads also to more robust feature points
      and is therefore slightly better than the [Formula: see text] voxel images
      (standard setting of device). Our comparison of two different artifact reduction
      methods and the complete removal of metal in the images shows that our approach
      is highly robust against artifacts and the number and position of metal implants.
      CONCLUSIONS: By introducing our fast algorithmic processing pipeline, we
      developed the first steps for a fully automatic assistance system for the
      assessment of C-arm CT images.

PMID- 26316066
TI  - An N-Acetyl Cysteine Ruthenium Tricarbonyl Conjugate Enables Simultaneous Release
      of CO and Ablation of Reactive Oxygen Species.
AB  - We have designed and synthesised a [Ru(CO)3 Cl2 (NAC)] pro-drug that features an
      N-acetyl cysteine (NAC) ligand. This NAC carbon monoxide releasing molecule
      (CORM) conjugate is able to simultaneously release biologically active CO and to
      ablate the concurrent formation of reactive oxygen species (ROS). Complexes of
      the general formulae [Ru(CO)3 (L)3 ](2+) , including [Ru(CO)3 Cl(glycinate)]
      (CORM-3), have been shown to produce ROS through a water-gas shift reaction,
      which contributes significantly, for example, to their antibacterial activity. In
      contrast, NAC-CORM conjugates do not produce ROS or possess antibacterial
      activity. In addition, we demonstrate the synergistic effect of CO and NAC both
      for the inhibition of nitric oxide (formation) and in the expression of tumour
      necrosis factor (TNF)-alpha. This work highlights the advantages of combining a
      CO-releasing scaffold with the anti-oxidant and anti-inflammatory drug NAC in a
      unique pro-drug. 

PMID- 26316067
TI  - European laws on compulsory commitment to care of persons suffering from
      substance use disorders or misuse problems- a comparative review from a human and
      civil rights perspective.
AB  - BACKGROUND: Laws on compulsory commitment to care (CCC) in mental health, social
      and criminal legislation for adult persons with alcohol and/or drug dependence or
      misuse problems are constructed to address different scenarios related to
      substance use disorders. This study examines how such CCC laws in European states
      vary in terms of legal rights, formal orders of decision and criteria for
      involuntary admission, and assesses whether three legal frameworks (criminal,
      mental and social law) equally well ensure human and civil rights. METHODS:
      Thirty-nine laws, from 38 countries, were analysed. Respondents replied in web
      based questionnaires concerning a) legal rights afforded the persons with
      substance use problems during commitment proceedings, b) sources of formal
      application, c) instances for decision on admission, and d) whether or not 36
      different criteria could function as grounds for decisions on CCC according to
      the law in question. Analysis of a-c were conducted in bivariate cross
      tabulations. The 36 criteria for admission were sorted in criteria groups based
      on principal component analysis (PCA). To investigate whether legal rights,
      decision-making authorities or legal criteria may discriminate between types of
      law on CCC, discriminant analyses (DA) were conducted. RESULTS: There are few
      differences between the three types of law on CCC concerning legal rights
      afforded the individual. However, proper safeguards of the rights against
      unlawful detention seem still to be lacking in some CCC laws, regardless type of
      law. Courts are the decision-making body in 80 % of the laws, but this varies
      clearly between law types. Criteria for CCC also differ between types of law,
      i.e. concerning who should be treated: dependent offenders, persons with
      substance use problems with acting out or aggressive behaviors, or other
      vulnerable persons with alcohol or drug problems. CONCLUSION: The study raises
      questions concerning whether various European CCC laws in relation to substance
      use disorder or misuse problems comply with international ratified conventions
      concerning human and civil rights. This, however, applies to all three types of
      law, i.e. social, mental health and criminal legislation. The main differences
      between law types concern legal criteria, reflecting different national
      priorities on implicit ambitions of CCC - for correction, for prevention, or for
      support to those in greatest need of care.

PMID- 26316069
TI  - Association between Atopic Dermatitis and Depression in US Adults.

PMID- 26316068
TI  - The collagen receptor uPARAP/Endo180 in tissue degradation and cancer (Review).
AB  - The collagen receptor uPARAP/Endo180, the product of the MRC2 gene, is a central
      component in the collagen turnover process governed by various mesenchymal cells.
      Through the endocytosis of collagen or large collagen fragments, this recycling
      receptor serves to direct basement membrane collagen as well as interstitial
      collagen to lysosomal degradation. This capacity, shared only with the mannose
      receptor from the same protein family, endows uPARAP/Endo180 with a critical role
      in development and homeostasis, as well as in pathological disruptions of the
      extracellular matrix structure. Important pathological functions of
      uPARAP/Endo180 have been identified in various cancers and in several fibrotic
      conditions. With a particular focus on matrix turnover in cancer, this review
      presents the necessary background for understanding the function of
      uPARAP/Endo180 at the molecular and cellular level, followed by an in-depth
      survey of the available knowledge of the expression and role of this receptor in
      various types of cancer and other degenerative diseases.

PMID- 26316070
TI  - Platelet-Activating Factor Induces Epigenetic Modifications in Human Mast Cells.
AB  - UV radiation-induced systemic immune suppression is a major risk factor for skin
      cancer induction. The migration of dermal mast cells from the skin to the
      draining lymph nodes has a prominent role in activating systemic immune
      suppression. UV-induced keratinocyte-derived platelet-activating factor (PAF)
      activates mast cell migration, in part by upregulating the expression of CXCR4 on
      the surface of mast cells. Others have indicated that epigenetic mechanisms
      regulate CXCR4 expression; therefore, we asked whether PAF activates epigenetic
      mechanisms in mast cells. Human mast cells were treated with PAF, and the effect
      on DNA methylation and/or acetylation was measured. PAF suppressed the expression
      of DNA methyltransferase (DNMT) 1 and 3b. On the other hand, PAF increased p300
      histone acetyltransferase expression, and the acetylation of histone H3, which
      coincided with a decreased expression of the histone deacetylase HDAC2. Chromatin
      immunoprecipitation assays indicated that PAF treatment activated the acetylation
      of the CXCR4 promoter. Finally, inhibiting histone acetylation blocked p300
      upregulation and suppressed PAF-induced surface expression of CXCR4. Our findings
      suggest a novel molecular mechanism for PAF, activation of epigenetic
      modifications. We suggest that PAF may serve as an endogenous molecular mediator
      that links the environment (UV radiation) with the epigenome. 

PMID- 26316071
TI  - Hydrogen sulfide synthesis enzymes reduced in lower esophageal sphincter of
      patients with achalasia.
AB  - The etiology of achalasia remains largely unknown. Considerable evidence reveals
      that the lower esophageal sphincter dysfunction is due to the lack of inhibitory
      neurotransmitter, secondary to esophageal neuronal inflammation or loss. Recent
      studies suggest hydrogen sulfide may act as an inhibitory transmitter in
      gastrointestinal tract, but study about hydrogen sulfide in human esophagus still
      lack. The aim of the study was to investigate if hydrogen sulfide synthesis
      enzymes could be detected in human esophagus and if the synthesis of the
      endogenous hydrogen sulfide could be affected in achalasia patients. Tissue
      samples in cardia, lower esophageal sphincter, 2 cm and 4 cm above lower
      esophageal sphincter were obtained from achalasia patients undergoing peroral
      endoscopic myotomy. Control tissues in lower esophageal sphincter were obtained
      from esophageal carcinoma patients. Expression of cystathionine-beta-synthase and
      cystathionine-gamma-lyase in lower esophageal sphincter of achalasia patients and
      control were detected by immunohistochemical staining. In addition, expression of
      cystathionine-beta-synthase and cystathionine-gamma-lyase were compared among
      different parts of esophagus in achalasia patients. Compared with control, the
      expression of cystathionine-beta-synthase and cystathionine-gamma-lyase in lower
      esophageal sphincter of achalasia patients was significantly reduced (chi2 =
      11.429, P = 0.010). The expression of cystathionine-beta-synthase and
      cystathionine-gamma-lyase were lower in lower esophageal sphincter than that in 2
      cm and 4 cm above lower esophageal sphincter, respectively (all P < 0.05). In
      conclusion, the expression of hydrogen sulfide synthesis enzymes, cystathionine
      beta-synthase and cystathionine-gamma-lyase, can be detected in human esophagus
      and is reduced in patients with achalasia, which implicates the involvement of
      the two hydrogen sulfide synthesis enzymes in the pathophysiology of achalasia.

PMID- 26316072
TI  - Reconstruction of Defects Involving the Nasal Ala and the Nasolabial Fold: The
      Role of the Microvascular Prehelical Rim Graft.
AB  - PURPOSE: To demonstrate a surgical technique for reconstructing defects involving
      the triangle of the nasal ala, nasolabial fold and upper lip. PROCEDURE:
      Retrospective survey with follow-up including 4 consecutive patients with
      extensive skin and soft tissue defects. RESULTS: Successful reconstruction with
      good nasal function and acceptable cosmetic result was achieved in all patients.
      CONCLUSION: The microvascular helical rim graft offers a unique option to
      reconstruct defects in this specific triangular area of the face when standard
      techniques have failed.

PMID- 26316073
TI  - In vitro Detection of Occlusal Caries on Permanent Teeth by a Visual, Light
      Induced Fluorescence and Photothermal Radiometry and Modulated Luminescence
      Methods.
AB  - BACKGROUND: The paradigm shift towards the nonsurgical management of dental
      caries relies on the early detection of the disease. Detection of caries at an
      early stage is of unequivocal importance for early preventive intervention.
      OBJECTIVE: The aim of this in vitro study is to evaluate the performance of a
      visual examination using the International Caries Detection and Assessment System
      (ICDAS) criteria, two quantitative light-induced fluorescence (QLF) systems-
      InspektorTM Pro and QLF-D BiluminatorTM 2 (Inspektor Research Systems B.V.,
      Amsterdam, The Netherlands)--and a photothermal radiometry and modulated
      luminescence, The Canary System(r) (Quantum Dental Technologies, Toronto, Ont.,
      Canada) on the detection of primary occlusal caries on permanent teeth. METHODS:
      A total of 60 teeth with occlusal surface sites ranging from sound to
      noncavitated lesions (ICDAS 0-4) were assessed with each detection method twice
      in a random order. Histological validation was used to compare methods for
      sensitivity, specificity, percent correct, and the area under the receiver
      operating characteristic curve (AUC), at standard and optimum sound thresholds.
      Interexaminer agreement and intraexaminer repeatability were measured using
      intraclass correlation coefficients. RESULTS: Interexaminer agreement ranged
      between 0.48 (The Canary System(r)) and 0.96 (QLF-D BiluminatorTM 2).
      Intraexaminer repeatability ranges were 0.33-0.63 (The Canary System(r)) and 0.96
      0.99 (QLF-D BiluminatorTM 2). The sensitivity range was 0.75-0.96 while that of
      specificity was 0.43-0.89. The AUC were 0.79 (The Canary System(r)), 0.87
      (ICDAS), 0.90 (InspektorTM Pro), and 0.94 (QLF-D BiluminatorTM 2). CONCLUSION:
      ICDAS had the best combination of sensitivity and specificity followed by QLF-D
      BiluminatorTM 2 at optimum threshold.

PMID- 26316074
TI  - Accumulation of mannitol in the cytoplasm and vacuole during the expansion of
      sepal cells associated with flower opening in Delphinium * belladonna cv.
      Bellamosum.
AB  - MAIN CONCLUSION: The role of mannitol differs from that of glucose, fructose and
      sucrose in sepal cell expansion associated with flower opening in Delphinium *
      belladonna. Sepals of Delphinium * belladonna are colored and much larger than
      the petals. To determine whether the role of mannitol in sepal growth associated
      with flower opening differs from those of ubiquitous metabolic sugars including
      glucose, fructose and sucrose, we investigated changes in cell number,
      subcellular concentrations of soluble carbohydrates, and osmotic potential in
      sepals during flower opening in Delphinium * belladonna cv. Bellamosum. The
      number of epidermal cells in the sepals did not increase from the stage when
      sepal pigmentation started, whereas the cell area increased during flower
      opening, indicating that petal growth during flower opening depends on cell
      expansion. Mannitol concentrations in the vacuole at three different stages were
      approximately 100 mM, which were much higher than the other carbohydrate
      concentrations, but they decreased slightly at open stage. In contrast, mannitol
      concentration in the cytoplasm was 56 mM at bud stage, but it increased to 104 mM
      at open stage. Glucose and fructose concentrations in the vacuole at open stage
      increased to 45 and 56 mM, respectively. Total osmotic potential in apoplast and
      symplast, which was partially due to soluble carbohydrates, was almost constant
      during flower opening. Therefore, mannitol may be acting constitutively as the
      main osmoticum in the vacuole where it may contribute to the maintenance of the
      osmotic balance between the cytoplasm and vacuole in open flowers. The role of
      mannitol differs from those of glucose, fructose, and sucrose in sepal cell
      expansion in Delphinium * belladonna.

PMID- 26316075
TI  - HBx triggers either cellular senescence or cell proliferation depending on
      cellular phenotype.
AB  - Replicative senescence is a hallmark of chronic liver diseases including chronic
      hepatitis B virus (HBV) infection, whereas HBV-encoded oncoproteins HBx and preS2
      have been found to overcome senescence. HBx possesses a C-terminal truncation
      mainly in hepatocellular carcinomas but also in noncancerous liver tissues. Here,
      by cell counting, BrdU incorporation, MTT proliferation assay, cell cycle
      analysis, SA-betagal staining and Western blotting in primary and malignant
      cells, we investigated the effect of HBx C-terminal mutants on cellular
      senescence. HBx C-terminal mutants were found to trigger cellular senescence in
      primary MRC5 cells, and malignant liver cells Huh7, and SK-Hep1. In contrast,
      these mutants promoted the proliferation of HepG2 malignant liver cells. The pro
      senescent effect of HBx relied on an increased p16(INK4a) and p21(Waf1/Cip1)
      expression, and a decreased phosphorylation of Rb. Together, these results
      suggest that the two main variants of HBx present in HBV-infected liver possess
      opposite effects on cellular senescence that depend on the phenotype of infected
      cells.

PMID- 26316076
TI  - Real-time monitoring of oxidative etching on single Ag nanocubes via light
      scattering dark-field microscopy imaging.
AB  - A low-cost and easily-conducted light-scattering dark-field microscopy imaging
      (iDFM) technique for real-time and in situ monitoring of the oxidative etching on
      a single Ag nanocube was presented by using an ordinary dark-field microscopy
      system, which provides an alternative approach to study the behaviors of metal
      nanoparticles in chemical reactions and biological processes at the single
      nanoparticle level. 

PMID- 26316078
TI  - Nobiletin Stimulates Chloride Secretion in Human Bronchial Epithelia via a
      cAMP/PKA-Dependent Pathway.
AB  - BACKGROUND/AIMS: Nobiletin, a citrus flavonoid isolated from tangerines, alters
      ion transport functions in intestinal epithelia, and has antagonistic effects on
      eosinophilic airway inflammation of asthmatic rats. The present study examined
      the effects of nobiletin on basal short-circuit current (I(SC)) in a human
      bronchial epithelial cell line (16HBE14o-), and characterized the signal
      transduction pathways that allowed nobiletin to regulate electrolyte transport.
      METHODS: The I(SC) measurement technique was used for transepithelial electrical
      measurements. Intracellular calcium ([Ca(2+)]i) and cAMP were also quantified.
      RESULTS: Nobiletin stimulated a concentration-dependent increase in I(SC), which
      was due to Cl- secretion. The increase in I(SC) was inhibited by a cystic
      fibrosis transmembrane conductance regulator inhibitor (CFTR(inh)-172), but not
      by 4,4'-diisothiocyano-stilbene-2,2'-disulphonic acid (DIDS), Chromanol 293B,
      clotrimazole, or TRAM-34. Nobiletin-stimulated I(SC) was also sensitive to a
      protein kinase A (PKA) inhibitor, H89, and an adenylate cyclase inhibitor, MDL
      12330A. Nobiletin could not stimulate any increase in I(SC) in a cystic fibrosis
      (CF) cell line, CFBE41o-, which lacked a functional CFTR. Nobiletin stimulated a
      real-time increase in cAMP, but not [Ca(2+)]i. CONCLUSION: Nobiletin stimulated
      transepithelial Cl- secretion across human bronchial epithelia. The mechanisms
      involved activation of adenylate cyclase- and cAMP/PKA-dependent pathways,
      leading to activation of apical CFTR Cl- channels.

PMID- 26316077
TI  - Colistin-Induced Apoptosis of Neuroblastoma-2a Cells Involves the Generation of
      Reactive Oxygen Species, Mitochondrial Dysfunction, and Autophagy.
AB  - Neurotoxicity remains a poorly characterized adverse effect associated with
      colistin therapy. The aim of the present study was to investigate the mechanism
      of colistin-induced neurotoxicity using the mouse neuroblastoma2a (N2a) cell
      line. Colistin treatment (0-200 MUM) of N2a neuronal cells induced apoptotic cell
      death in a dose-dependent manner. Colistin-induced neurotoxicity was associated
      with a significant increase of reactive oxygen species (ROS) levels, with a
      concomitant decrease in the activities of superoxide dismutase (SOD), catalase
      (CAT), and the glutathione (GSH) levels. Mitochondrial dysfunction was evident
      from the dissipation of membrane potential and the increase of Bax/Bcl-2,
      followed by the release of cytochrome c (CytC). Caspase-3/7, -8, and -9
      activations were also detected. Colistin-induced neurotoxicity significantly
      increased the gene expression of p53 (1.6-fold), Bax (3.3-fold), and caspase-8
      (2.2-fold) (all p < 0.01). The formation of autophagic vacuoles was evident with
      the significant increases (all p < 0.05 or 0.01) of both of Beclin 1 and LC3B
      following colistin treatment (50-200 MUM). Furthermore, inhibition of autophagy
      by pretreatment with chloroquine diphosphate (CQ) enhanced colistin-induced
      apoptosis via caspase activation, which could be attenuated by co-treatment with
      the pan-caspase inhibitor Z-VAD-FMK. In summary, our study reveals that colistin
      induced neuronal cell death involves ROS-mediated oxidative stress and
      mitochondrial dysfunction, followed by caspase-dependent apoptosis and autophagy.
      A knowledge base of the neuronal signaling pathways involved in colistin-induced
      neurotoxicity will greatly facilitate the discovery of neuroprotective agents for
      use in combination with colistin to prevent this undesirable side effect.

PMID- 26316079
TI  - Therapeutic Effects of Transplantation of As-MiR-937-Expressing Mesenchymal Stem
      Cells in Murine Model of Alzheimer's Disease.
AB  - BACKGROUND/AIMS: Alzheimer's disease (AD) is one of the most common dementias
      among aged people, and is clinically characterized by progressive memory loss,
      behavioral and learning dysfunction and cognitive deficits. So far, this is no
      cure for AD. A therapeutic effect of transplantation of mesenchymal stem cells
      (MSCs) into murine model of AD has been reported, but remains to be further
      improved. Brn-4 is a transcription factor that plays a critical role in neuronal
      development, whereas the effects of Brn-4 overexpression in transplanted MSCs on
      AD are unknown. METHODS: MSCs were isolated from mouse bone marrow and induced to
      overexpress antisense of miRNA-937 (as-miR-937) through adeno-associated virus
      (AAV)-mediated transduction, and purified by flow cytometry based on expression
      of a GFP co-transgene in the cells. The Brn-4 levels in mouse MSCs were examined
      in miR-937-modified MSCs by RT-qPCR and by Western blot. These miR-937-modified
      MSCs were then transplanted into an APP/PS1 transgenic AD model in mice. The
      effects of saline control, MSCs and asmiR-937 MSCs on AD mice were examined by
      deposition of amyloid-beta peptide aggregates (Abeta), social recognition test
      (SR), Plus-Maze Discriminative Avoidance Task (PM-DAT) and the levels of Brain
      derived neurotrophic factor (BDNF) in the mouse brain. RESULTS: MSCs expressed
      high levels of Brn-4 transcripts but low levels of Brn-4 protein. Poor protein vs
      mRNA levels of Brn-4 in MSCs appeared to result from the presence of high levels
      of miR-937 in MSCs. miR-937 inhibited translation of Brn-4 mRNA through binding
      to the 3'-UTR of the Brn-4 mRNA in MSCs. Expression of as-miR-937 significantly
      increased Brn-4 protein levels in MSCs. Transplantation of as-miR-937-expressing
      MSCs significantly reduced the deposition of Abeta, increased the levels of BDNF,
      and significantly improved the appearance in SR and PM-DAT in AD mice.
      CONCLUSION: Overexpression of as-miR-937 in MSCs may substantially improve the
      therapeutic effects of MSCs on AD, possibly through augmenting Brn-4 levels in
      MSCs.

PMID- 26316080
TI  - Clofazimine Induced Suicidal Death of Human Erythrocytes.
AB  - BACKGROUND/AIMS: The antimycobacterial riminophenazine clofazimine has previously
      been shown to up-regulate cellular phospholipase A2 and to induce apoptosis. In
      erythrocytes phospholipase A2 stimulates eryptosis, the suicidal erythrocyte
      death characterized by cell shrinkage and cell membrane scrambling with
      phosphatidylserine translocation to the erythrocyte surface. Phospholipase A2 is
      in part effective by fostering formation of prostaglandin E2, which triggers
      Ca(2+) entry. Stimulators of Ca(2+) entry and eryptosis further include oxidative
      stress and energy depletion. The present study tested, whether and how
      clofazimine induces eryptosis. METHODS: Phosphatidylserine exposure at the cell
      surface was estimated from annexin V binding, cell volume from forward scatter,
      hemolysis from hemoglobin release, cytosolic Ca(2+) activity ([Ca(2+)]i) from
      Fluo3-fluorescence, reactive oxygen species (ROS) from 2', 7'
      dichlorodihydrofluorescein diacetate (DCFDA) fluorescence, and cytosolic ATP
      level utilizing a luciferin-luciferase assay kit. RESULTS: A 24-48 hours exposure
      of human erythrocytes to clofazimine (>= 1.5 ug/ml) significantly increased the
      percentage of annexin-V-binding cells without appreciably modifying forward
      scatter. Clofazimine significantly increased [Ca(2+)]i, significantly decreased
      cytosolic ATP, but did not significantly modify ROS. The effect of clofazimine on
      annexin-V-binding was significantly blunted, but not fully abolished by removal
      of extracellular Ca(2+), and by phospholipase A2 inhibitor quinacrine (25 uM).
      Clofazimine further augmented the effect of Ca(2+) ionophore ionomycin (0.1 uM)
      on eryptosis. The clofazimine induced annexin-V-binding was, however, completely
      abrogated by combined Ca(2+) removal and addition of quinacrine. CONCLUSION:
      Clofazimine stimulates phospholipid scrambling of the erythrocyte cell membrane,
      an effect in part dependent on entry of extracellular Ca(2+), paralleled by
      cellular energy depletion and sensitive to phospholipase A2 inhibitor quinacrine.

PMID- 26316081
TI  - MiR-497 Suppresses YAP1 and Inhibits Tumor Growth in Non-Small Cell Lung Cancer.
AB  - BACKGROUND/AIMS: To investigate the expression, clinical significance and the
      cellular effects of miR-497 in non-small cell lung cancer (NSCLC). METHODS: NSCLC
      cells were transiently transfected with miR-497 mimics or siRNA to up-regulate or
      down-regulate expression. Quantitative real-time PCR (qRT-PCR) was used to detect
      the mRNA level of miR-497. Luciferase assays, colony formation assays and BrdU
      incorporation assays were performed to identify the targets and role of miR-497
      in NSCLC cells. Finally, the abundance of miR-497 was analyzed in a total of 51
      NSCLC specimens. RESULTS: The transcript levels of miR-497 were significantly
      decreased in NSCLC tissue (25/30; 83.3%). Low miR-497 levels in tumor tissue
      correlated with advanced pT stage. Additionally, miR-497 transcript levels
      correlated with overall survival of NSCLC patients (n = 51, p = 0.022).
      Overexpression of miR-497 inhibited the proliferation of NSCLC cell and down
      regulation of miR-497 resulted in elevated NSCLC growth. Exogenous over
      expression of YAP1 partially eliminated miR-497-induced cell growth. CONCLUSION:
      miR-497 plays an important role in inhibiting the proliferation of NSCLC by
      targeting YAP1. Our results suggest that miR-497 is a potential therapeutic
      target in treating patients with NSCLC.

PMID- 26316082
TI  - Removal of Potential Phosphorylation Sites does not Alter Creatine Transporter
      Response to PKC or Substrate Availability.
AB  - BACKGROUND: Creatine, Phosphocreatine, and creatine kinases, constitute an energy
      shuttle that links ATP production in mitochondria with cellular consumption
      sites. Myocytes and neurons cannot synthesize creatine and depend on uptake
      across the cell membrane by a specialized transporter to maintain intracellular
      creatine levels. Although recent studies have improved our understanding of
      creatine transport in cardiomyocytes, the structural elements underlying the
      creatine transporter protein regulation and the relevant intracellular signaling
      processes are unknown. METHODS: The effects of pharmacological activation of
      kinases or phosphatases on creatine transport in cardiomyocytes in culture were
      evaluated. Putative phosphorylation sites in the creatine transporter protein
      were identified by bioinformatics analyses, and ablated using site-directed
      mutagenesis. Mutant transporter function and their responses to pharmacological
      PKC activation or changes in creatine availability in the extracellular
      environment, were evaluated. RESULTS: PKC activation decreases creatine transport
      in cardiomyocytes in culture. Elimination of high probability potential
      phosphorylation sites did not abrogate responses to PKC activation or substrate
      availability. CONCLUSION: Modulation of creatine transport in cardiomyocytes is a
      complex process where phosphorylation at predicted sites in the creatine
      transporter protein does not significantly alter activity. Instead, non-classical
      structural elements in the creatine transporter and/or interactions with
      regulatory subunits may modulate its activity.

PMID- 26316083
TI  - 8-Methoxypsoralen Induces Intrinsic Apoptosis in HepG2 Cells: Involvement of
      Reactive Oxygen Species Generation and ERK1/2 Pathway Inhibition.
AB  - BACKGROUND/AIMS: 8-Methoxypsoralen (8-MOP), a formerly considered
      photosensitizing agent, induces apoptosis when used alone. On this basis, the
      present study was designed to explore the effects and mechanisms of 8-MOP-induced
      apoptosis in human hepatocellular carcinoma HepG2 cells, independent of its
      photoactivation. METHODS: We analyzed the cell viability with MTT assay. Flow
      cytometry was used to examine the apoptosis rate, mitochondrial membrane
      potential (MMP) and reactive oxygen species (ROS) generation after specific
      staining. The expression and location of apoptosis-associated protein as well as
      the activation status of cell signaling pathway were determined by Western blot
      analysis. RESULTS: 8-MOP significantly decreased cell viability and induced cell
      apoptosis through mitochondrial apoptotic pathway, as demonstrated by increased
      Bax/Bcl-2 ratio, collapsed MMP, and induced cytochrome c release (Cyt c) and
      apoptosis-inducing factor (AIF) transposition. ROS generation was significantly
      increased by 8-MOP and the eradication of ROS significantly abolished 8-MOP
      induced apoptosis. In addition, the activation of ERK1/2 was drastically
      decreased by 8-MOP as ERK inhibitor PD98059, indicating a role of ERK1/2
      signaling pathway in 8-MOP-induced cell apoptosis. CONCLUSION: 8-MOP induces
      intrinsic apoptosis by increasing ROS generation and inhibiting ERK1/2 pathway in
      HepG2 cells. The findings are important in substantiating the anti-tumor role of
      8-MOP in cancer therapy.

PMID- 26316085
TI  - Up-Regulation of MiR-452 Inhibits Metastasis of Non-Small Cell Lung Cancer by
      Regulating BMI1.
AB  - BACKGROUND/AIMS: MicroRNAs (miRNAs) have been regarded as a new class of
      regulators in cellular processes in non-small cell lung cancer (NSCLC). However,
      the relationship between miR-452 and the development of NSCLC remains unclear.
      METHODS: qRT-PCR was used to detect the expression of miR-452 and its target gene
      in NSCLC samples (n=60). The transwell assay was used to test the cell invasion
      capability. The regulation mechanism was confirmed by luciferase reporter assay
      and western blot assay. RESULTS: In the current study, a relatively lower miR-452
      and higher BMI1 expression levels were confirmed to be associated with advanced
      tumor stage and more extent of lymph nodes metastasis. In vitro, down-regulated
      miR-452 could enhance cell invasion capability. Furthermore, miR-452 modulated
      BMI1 expression by binding to its 3'-UTR. The enhancement of cell invasion
      capability induced by down-regulated miR-452 was eliminated by repression of
      BMI1. CONCLUSIONS: Our results suggest that miR-452 plays a vital role in
      development of NSCLC, and this miR-452-BMI1 pathway might generate a novel
      insight into the treatment of NSCLC.

PMID- 26316084
TI  - MicroRNA-340 Inhibits Esophageal Cancer Cell Growth and Invasion by Targeting
      Phosphoserine Aminotransferase 1.
AB  - BACKGROUND/AIMS: Emerging evidence indicates that microRNA (miR)-340 is
      downregulated in various human cancers, suggesting that it acts as a tumor
      suppressor. The aim of the present study was to evaluate the expression and role
      of miR-340 in human esophageal squamous cell carcinoma (ESCC). METHODS: The
      expression of miR-340 was examined in 64 paired ESCC and adjacent non-tumor
      tissues by quantitative real time PCR. The effects of miR-340 on ESCC cell
      proliferation and metastasis were examined by MTT and Matrigel invasion assays.
      Tumor growth was assessed by subcutaneous inoculation of cells into BALB/c nude
      mice. Targets of miR-340 were identified by bioinformatics and verified by
      luciferase reporter assays, quantitative real-time PCR, and western blotting.
      RESULTS: MiR-340 was significantly downregulated in ESCC tumor tissues compared
      to adjacent non-tumor tissues and in ESCC cell lines compared to esophageal
      endothelial cells. Overexpression of miR-340 inhibited ESCC cell growth, colony
      formation, and invasion, and tumor growth in a xenograft mouse model. PSAT1 was
      identified as a direct target of miR-340 and its ectopic expression partially
      reversed the miR-340 mediated inhibition of viability, invasion and EMT in ESCC
      cells. The expression of miR-340 was negatively correlated with that of PSAT1 in
      human ESCC samples. CONCLUSION: MiR-340 functions as a tumor suppressor by
      modulating the expression of PSAT1 and may contribute to the progression and
      invasiveness of ESCC.

PMID- 26316086
TI  - Chorein Sensitive Arrangement of Cytoskeletal Architecture.
AB  - BACKGROUND/AIMS: Chorein is a protein expressed in various cell types. Loss of
      function mutations of the chorein encoding gene VPS13A lead to chorea
      acanthocytosis, an autosomal recessive genetic disease characterized by movement
      disorder and behavioral abnormalities. Recent observations revealed that chorein
      is a powerful regulator of actin cytoskeleton in erythrocytes, platelets, K562
      and endothelial HUVEC cells. METHODS: In the present study we have used Western
      blotting to study actin polymerization dynamics, laser scanning microscopy to
      evaluate in detail the role of chorein in microfilaments, microtubules and
      intermediate filaments cytoskeleton architecture and RT-PCR to assess gene
      transcription of the cytoskeletal proteins. RESULTS: We report here powerful
      depolymerization of actin microfilaments both, in erythrocytes and fibroblasts
      isolated from chorea-acanthocytosis patients. Along those lines, morphological
      analysis of fibroblasts from chorea-acanthocytosis patients showed disarranged
      microtubular network, when compared to fibroblasts from healthy donors.
      Similarly, the intermediate filament networks of desmin and cytokeratins showed
      significantly disordered organization with clearly diminished staining in
      patient's fibroblasts. In line with this, RT-PCR analysis revealed significant
      downregulation of desmin and cytokeratin gene transcripts. CONCLUSION: Our
      results provide for the first time evidence that defective chorein is accompanied
      by significant structural disorganization of all cytoskeletal structures in human
      fibroblasts from chorea-acanthocytosis patients.

PMID- 26316087
TI  - Predicted versus measured thoracic gas volumes of collegiate athletes made by the
      BOD POD air displacement plethysmography system.
AB  - Measured (TGVm) and predicted (TGVp) thoracic gas volumes from the BOD POD were
      compared in 33 lean, university athletes. On average, TGVp (3.529 L) was not
      significantly different (p = 0.343) from TGVm (3.628 L); however, there was a
      bias (r = -0.703, p < 0.001). The difference in the percentage of body fat (BF)
      was within +/-2% BF for 76% of the sample, but athletes at the extremes of height
      should have TGV measured. 

PMID- 26316088
TI  - Whole-Genome Sequencing of a Single Viral Species from a Highly Heterogeneous
      Sample.
AB  - Metagenomic studies suggest that only a small fraction of the viruses that exist
      in nature have been identified and studied. Characterization of unknown viral
      genomes is hindered by the many genomes populating any virus sample. A new method
      is reported that integrates drop-based microfluidics and computational analysis
      to enable the purification of any single viral species from a complex mixed virus
      sample and the retrieval of complete genome sequences. By using this platform,
      the genome sequence of a 5243 bp dsDNA virus that was spiked into wastewater was
      retrieved with greater than 96% sequence coverage and more than 99.8% sequence
      identity. This method holds great potential for virus discovery since it allows
      enrichment and sequencing of previously undescribed viruses as well as known
      viruses.

PMID- 26316089
TI  - Self-Reported Knee Instability Before and After Total Knee Replacement Surgery.
AB  - OBJECTIVE: To determine the prevalence and burden of pain and activity
      limitations associated with retaining presurgery self-reported knee instability 6
      months after total knee replacement (TKR) surgery and to identify early
      potentially modifiable risk factors for retaining knee instability in the
      operated knee after TKR surgery. METHODS: A secondary analysis was performed
      using measures obtained from 390 participants undergoing primary unilateral TKR
      and participating in a randomized clinical trial. Self-reported knee instability
      was measured using 2 items from the Activities of Daily Living Scale of the Knee
      Outcome Survey. Outcome measures were knee pain (range 0-20) and physical
      function (range 0-68) on the Western Ontario and McMaster Universities Arthritis
      Index (WOMAC), stair-climb power, 50-foot walk time, knee range of motion, and
      isometric knee flexion and extension strength. RESULTS: In this study, 72% of
      participants reported knee instability just prior to surgery, with 32% retaining
      instability in the operated knee 6 months after surgery. Participants retaining
      operated knee instability had significantly more knee pain and activity
      limitations 6 months after surgery, with mean +/- SD WOMAC scores of 4.8 +/- 3.7
      and 17.5 +/- 11.1, respectively, compared to participants without knee
      instability, with 2.9 +/- 3.1 and 9.8 +/- 9.2. The multivariable predictor model
      for retained knee instability included a high comorbidity score (>6), low stair
      climb power (<150 watts), more pain in the operated knee (>7 of 20), and younger
      age (<60 years). CONCLUSION: Self-reported knee instability is highly prevalent
      before and after TKR surgery and is associated with a considerable burden of pain
      and activity limitation in the operated knee. Increasing lower extremity muscle
      power may reduce the risk of retaining knee instability after TKR surgery.

PMID- 26316092
TI  - Reply.

PMID- 26316090
TI  - Nitric oxide inhibits larval settlement in Amphibalanus amphitrite cyprids by
      repressing muscle locomotion and molting.
AB  - Nitric oxide (NO) is a universal signaling molecule and plays a negative role in
      the metamorphosis of many biphasic organisms. Recently, the NO/cGMP (cyclic
      guanosine monophosphate) signaling pathway was reported to repress larval
      settlement in the barnacle Amphibalanus amphitrite. To understand the underlying
      molecular mechanism, we analyzed changes in the proteome of A. amphitrite cyprids
      in response to different concentrations of the NO donor sodium nitroprusside
      (SNP; 62.5, 250, and 1000 MUM) using a label-free proteomics method. Compared
      with the control, the expression of 106 proteins differed in all three
      treatments. These differentially expressed proteins were assigned to 13 pathways
      based on KEGG pathway enrichment analysis. SNP treatment stimulated the
      expression of heat shock proteins and arginine kinase, which are functionally
      related to NO synthases, increased the expression levels of glutathione
      transferases for detoxification, and activated the iron-mediated fatty acid
      degradation pathway and the citrate cycle through ferritin. Moreover, NO
      repressed the level of myosins and cuticular proteins, which indicated that NO
      might inhibit larval settlement in A. amphitrite by modulating the process of
      muscle locomotion and molting. 

PMID- 26316093
TI  - The moderating role of internalising negative emotionality in the relation of
      self-regulation to social adjustment in Italian preschool-aged children.
AB  - The purpose of this study was to examine the moderating role of internalising
      negative emotionality (i.e., anxious, concerned, and embarrassed displays) in the
      association between children's self-regulation and social adjustment. Seventy
      four Italian children (44 girls, 30 boys; M age = 35.05 months, SD = 3.57) were
      assessed using two self-regulation tasks. Internalising negative emotionality was
      assessed through observations of children's emotion expressions during the tasks.
      Teachers evaluated children's social competence and internalising and
      externalising problems. Results demonstrated that among children who exhibited
      internalising negative emotionality, self-regulation was positively associated
      with social competence and negatively related to externalising problems. Our
      results suggest that self-regulation may play a crucial role for social
      adjustment when children show emotions such as anxiety and embarrassment during
      challenging situations.

PMID- 26316094
TI  - Ole e 1, Ole e 7, and Ole e 9: Identifying distinct clinical subsets of olive
      tree-allergic patients.

PMID- 26316096
TI  - Further clinical trials on macrolides for bronchiolitis in infants are
      unnecessary.

PMID- 26316097
TI  - Spontaneous Dorsal Extramedullary Hematoma: A Rare Case Presenting as Isolated
      Thunderclap Headache.

PMID- 26316095
TI  - Alopecia areata profiling shows TH1, TH2, and IL-23 cytokine activation without
      parallel TH17/TH22 skewing.
AB  - BACKGROUND: Alopecia areata (AA) is a common T cell-mediated disorder with
      limited therapeutics. A molecular profile of cytokine pathways in AA tissues is
      lacking. Although studies have focused on TH1/IFN-gamma responses, several
      observations support a shared genetic background between AA and atopy. OBJECTIVE:
      We sought to define the AA scalp transcriptome and associated biomarkers with
      comparisons with atopic dermatitis (AD) and psoriasis. METHODS: We performed
      microarray and RT-PCR profiling of 27 lesional and 17 nonlesional scalp samples
      from patients with AA for comparison with normal scalp samples (n = 6). AA gene
      expression was also compared with samples from patients with lesional or
      nonlesional AD and those with psoriasis. A fold change of greater than 1.5 and a
      false discovery rate of less than 0.05 were used for differentially expressed
      genes (DEGs). RESULTS: We established the AA transcriptomes (lesional vs
      nonlesional: 734 DEGs [297 upregulated and 437 downregulated]; lesional vs
      normal: 4230 DEGs [1980 upregulated and 2250 downregulated]), including many
      upregulated immune and downregulated hair keratin genes. Equally impressive as
      upregulation in TH1/interferon markers (IFNG and CXCL10/CXCL9) were those noted
      in TH2 (IL13, CCL18, CCL26, thymic stromal lymphopoietin, and periostin), TH9/IL
      9, IL-23 (p40 and p19), and IL-16 mediators (all P < .05). There were no
      increases in TH17/TH22 markers. Hair keratin (KRT) expressions (ie, KRT86 and
      KRT85) were significantly suppressed in lesional skin. Greater scalp involvement
      (>25%) was associated with greater immune and keratin dysregulation and larger
      abnormalities in nonlesional scalp samples (ie, CXCL10 and KRT85). CONCLUSIONS:
      Our data associate the AA signature with TH2, TH1, IL-23, and IL-9/TH9 cytokine
      activation, suggesting consideration of anti-TH2, anti-TH1, and anti-IL-23
      targeting strategies. Similar to psoriasis and AD, clinical trials with selective
      antagonists are required to dissect key pathogenic pathways.

PMID- 26316098
TI  - Ultrasound-guided catheterisation of the subclavian vein: freehand vs needle
      guided technique.
AB  - The objective of this prospective, randomised study was to examine the impact of
      a multi-angle needle guide for ultrasound-guided, in-plane, central venous
      catheter placement in the subclavian vein. One hundred and sixty patients were
      randomly allocated to two groups, freehand or needle-guided, and then 159
      catheterisations were analysed. Cannulation of the first examined access site was
      successful in 96.9% of cases with no significant difference between groups. There
      were three arterial punctures and no other severe injuries. Catheter
      misplacements did not differ between the groups. Higher success rates within the
      first and second attempts in the needle-guided group were observed (p = 0.041 and
      p = 0.019, respectively). Use of the needle guide reduced the access time from a
      median (IQR [range]) of 30 (18-76 [6-1409]) s to 16 (10-30 [4-295]) s; p =
      0.0001, and increased needle visibility from 31.8% (9.7%-52.2% [0-96.67]) to
      86.2% (62.5%-100% [0-100]); p < 0.0001. A multi-angle needle guide significantly
      improved aligning the needle and ultrasound plane compared with the freehand
      technique when cannulating the subclavian vein. Use of the guide resulted in
      faster access times and increased success at the first and second attempts.

PMID- 26316099
TI  - Integrated bioethanol and biomanure production from potato waste.
AB  - Disposal of potato processing waste and the problem of pollution associated with
      it is a vital issue that is being faced by the potato processing plants. The
      conventional peeling methods presently followed in the processing plants for
      removing the potato peel, also result in the loss of some portion of the mash
      which is rich in starch. Indiscriminate discharge of the waste causes detrimental
      effects in the environment, so this problem can be resolved by successful
      utilization of the waste for the generation of value added products. Hence, the
      present work focuses on integrated production of bioethanol and biomanure to
      utilize the waste completely leading to zero waste generation. The first part of
      the work describes a comparative study of ethanol production from potato peel and
      mash wastes by employing co-culture of Aspergillus niger and Saccharomyces
      cerevisiae at various incubation time (24-120 h) instead of application of
      enzymes. The solid state fermentation of potato peel and mash inoculated with co
      culture, resulted in bioethanol production of 6.18% (v/v) and 9.30% (v/v)
      respectively. In the second part of the work, the residue obtained after ethanol
      production was inoculated with seven different microorganisms (Nostoc muscorum,
      Fischerella muscicola, Anabaena variabilis, Aulosira fertilissima,
      Cylindrospermum muscicola, Azospirillium lipoferum, Azotobacter chroococcum) and
      mixture of all the organisms in equal ratio for nitrogen (N), phosphorous (P) and
      potassium (K) enrichment. Among them, A. variabilis was found to enrich N, P and
      K content of the residue by nearly 7.66, 21.66 and 15 fold than that of the
      initial content, ultimately leading to improved N:P:K ratio of approximately
      2:1:1. The application of simultaneous saccharification and fermentation (SSF)
      for the conversion of potato waste to ethanol and enrichment of residue obtained
      after ethanol production with microorganisms to be used as manure envisages
      environmental sustainability.

PMID- 26316100
TI  - Synthesis of high-purity precipitated calcium carbonate during the process of
      recovery of elemental sulphur from gypsum waste.
AB  - We recently showed that the production of elemental sulphur and calcium carbonate
      (CaCO3) from gypsum waste by thermally reducing the waste into calcium sulphide
      (CaS) followed by its direct aqueous carbonation yielded low-grade carbonate
      products (i.e. <90 mass% as CaCO3). In this study, we used the insight gained
      from our previous work and developed an indirect aqueous CaS carbonation process
      for the production of high-grade CaCO3 (i.e. >99 mass% as CaCO3) or precipitated
      calcium carbonate (PCC). The process used an acid gas (H2S) to improve the
      aqueous dissolution of CaS, which is otherwise poorly soluble. The carbonate
      product was primarily calcite (99.5%) with traces of quartz (0.5%). Calcite was
      the only CaCO3 polymorph obtained; no vaterite or aragonite was detected. The
      product was made up of micron-size particles, which were further characterised by
      XRD, TGA, SEM, BET and true density. Results showed that about 0.37 ton of high
      grade PCC can be produced from 1.0 ton of gypsum waste, and generates about 0.19
      ton of residue, a reduction of 80% from original waste gypsum mass to mass of
      residue that needs to be discarded off. The use of gypsum waste as primary
      material in replacement of mined limestone for the production of PPC could
      alleviate waste disposal problems, along with converting significant volumes of
      waste materials into marketable commodities.

PMID- 26316101
TI  - Valorisation of fish by-products against waste management treatments--Comparison
      of environmental impacts.
AB  - Reuse and valorisation of fish by-products is a key process for marine resources
      conservation. Usually, fishmeal and oil processing factories collect the by
      products generated by fishing port and industry processing activities, producing
      an economical benefit to both parts. In the same way, different added-value
      products can be recovered by the valorisation industries whereas fishing
      companies save the costs associated with the management of those wastes. However,
      it is important to estimate the advantages of valorisation processes not only in
      terms of economic income, but also considering the environmental impacts. This
      would help to know if the valorisation of a residue provokes higher impact than
      other waste management options, which means that its advantages are probably not
      enough for guarantying a sustainable waste reuse. To that purpose, there are
      several methodologies to evaluate the environmental impacts of processes,
      including those of waste management, providing different indicators which give
      information on relevant environmental aspects. In the current study, a
      comparative environmental assessment between a valorisation process (fishmeal and
      oil production) and different waste management scenarios (composting,
      incineration and landfilling) was developed. This comparison is a necessary step
      for the development and industrial implementation of these processes as the best
      alternative treatment for fish by-products. The obtained results showed that both
      valorisation process and waste management treatments presented similar impacts.
      However, a significant benefit can be achieved through valorisation of fish by
      products. Additionally, the implications of the possible presence of pollutants
      were discussed. 

PMID- 26316102
TI  - Effect of moisture on pretreatment efficiency for anaerobic digestion of
      lignocellulosic substrates.
AB  - The present study evaluates the effect of moisture in low-temperature and
      ultrasound pretreatment on lignocellulosic substrates anaerobic biodegradability,
      where brewer's spent grain was used as model substrate. Besides moisture content,
      low-temperature pretreatment was also evaluated in terms of temperature (60-80
      degrees C) and exposure time (12-72 h). Likewise, ultrasonication was also
      evaluated in terms of specific energy (1000-50,000 kJ kg TS(-1)). In addition,
      the effect of substrate particle size reduction by milling pretreatment was also
      considered. The results clearly demonstrated that substrate moisture (total solid
      concentration) is a significant parameter for pretreatment performance, although
      it has been rarely considered in pretreatment optimisation. Specifically,
      moisture optimisation increased the methane yield of brewer's spent grain by 6%
      for low-temperature pretreatment (60 degrees C), and by 14% for ultrasound
      pretreatment (1000 kJ kg TS(-1)) towards the control (without pretreatment). In
      both pretreatments, the experimental optimum total solid concentration was 100
      gTS kg(-1). Thus, lowering substrate moisture, a strategy suggested attaining
      energetic pretreatment feasibility, needs to be analysed as another pretreatment
      variable since it might have limited correlation. Finally, a preliminary
      energetic balance of the pretreatments under study showed that the extra methane
      production could not cover the energetic pretreatment expenses.

PMID- 26316103
TI  - Up-regulation of Serum MiR-130b-3p Level is Associated with Renal Damage in Early
      Lupus Nephritis.
AB  - Systemic lupus erythematosus (SLE) is a common but severe autoimmune systemic
      inflammatory disease. Lupus nephritis (LN) is a serious complication of
      SLE,affecting up to 70% of SLE patients. Circulating microRNAs (miRNA) are
      emerging as biomarkers for pathological conditions and play significant roles in
      intercellular communication. In present research, serum samples from healthy
      control, early and late stage LN patients were used to analyze the expression
      profile of miRNAs by microarray. Subsequent study demonstrated that miR-130b-3p
      in serum of patients with early stage LN were significantly up-regulated when
      compared with healthy controls. In addition,we have also observed that the
      expression of a large amount of circulating microRNAs significantly decreased in
      patients with late stage LN. The further analysis found that the expression of
      serum miR-130b-3p was positively correlated with 24-hour proteinuria and renal
      chronicity index in patients with early stage LN.Transfection of renal tubular
      cellline(HK-2)with miR-130b-3p mimics can promote epithelial-mesenchymal
      transition (EMT). The opposite effects were observed when transfected with miR
      130b-3p inhibitors. MiR-130b-3p negatively regulated ERBB2IP expression by
      directly targeting the 3'-UTR of ERBB2IP The circulating miR-130b-3p might serve
      as a biomarker and play an important role in renal damage in early stage LN
      patients. 

PMID- 26316104
TI  - Variations in inflammatory genes as molecular markers for prediction of
      inflammatory bowel disease occurrence.
AB  - OBJECTIVE: Research on inflammatory bowel disease (IBD) has highlighted genes
      involved in the regulation of inflammatory responses as contributors to disease
      pathogenesis. This study aimed to evaluate the associations between IBD and
      variations in NOD2, TLR4, TNF-alpha, IL-6, IL-1beta and IL-1RN genes, and to use
      the genetic data obtained in predictive modeling. METHODS: A total of 167 IBD
      patients and 101 healthy controls were genotyped by polymerase chain reaction
      restriction fragment length polymorphism. Using the genotype data attained as the
      input to various classification algorithms, IBD prediction models were designed.
      The area under the receiver operating characteristic curve (AUROC) was used to
      measure their performance. RESULTS: Significant associations were found between
      Crohn's disease (CD) and minor NOD2 variants, as well as TLR4 299Gly, TNF-alpha G
      308A, IL-6 G-174C and IL-1RN VNTR A2 variants, while ulcerative colitis (UC) was
      associated only with IL-1RN VNTR A2 variants. CD and UC showed highly significant
      difference in the allelic distribution of TNF-alpha G-308A, where the A allele
      was found to be related to CD, and the G allele to UC. A combined effect of
      patients' gender and TLR4 variants was observed among CD patients. When all
      analyzed genotype and gender data were used, prediction performance achieved a
      maximum AUROC of 0.690 for CD and 0.601 for UC dataset. CONCLUSION: Variations in
      the genes involved in immune regulation are genetic factors of importance in IBD
      susceptibility that could potentially be used as predictors of disease
      development.

PMID- 26316105
TI  - Evaluation of optimized bronchoalveolar lavage sampling designs for
      characterization of pulmonary drug distribution.
AB  - Bronchoalveolar lavage (BAL) is a pulmonary sampling technique for
      characterization of drug concentrations in epithelial lining fluid and alveolar
      cells. Two hypothetical drugs with different pulmonary distribution rates (fast
      and slow) were considered. An optimized BAL sampling design was generated
      assuming no previous information regarding the pulmonary distribution (rate and
      extent) and with a maximum of two samples per subject. Simulations were performed
      to evaluate the impact of the number of samples per subject (1 or 2) and the
      sample size on the relative bias and relative root mean square error of the
      parameter estimates (rate and extent of pulmonary distribution). The optimized
      BAL sampling design depends on a characterized plasma concentration time profile,
      a population plasma pharmacokinetic model, the limit of quantification (LOQ) of
      the BAL method and involves only two BAL sample time points, one early and one
      late. The early sample should be taken as early as possible, where concentrations
      in the BAL fluid >= LOQ. The second sample should be taken at a time point in the
      declining part of the plasma curve, where the plasma concentration is equivalent
      to the plasma concentration in the early sample. Using a previously described
      general pulmonary distribution model linked to a plasma population
      pharmacokinetic model, simulated data using the final BAL sampling design enabled
      characterization of both the rate and extent of pulmonary distribution. The
      optimized BAL sampling design enables characterization of both the rate and
      extent of the pulmonary distribution for both fast and slowly equilibrating
      drugs.

PMID- 26316106
TI  - Severe extra-articular manifestations of rheumatoid arthritis in absence of
      concomitant joint involvement following long-term spontaneous remission. A case
      report.
AB  - Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease
      occasionally associated with severe extra-articular manifestations, mostly in
      cases of longstanding highly active disease. We report the case of a 56 year-old
      woman diagnosed with active RA at the age of 40. After 5 years of high activity,
      her arthritis subsides spontaneously during pregnancy despite the lack of
      treatment with disease-modifying anti-rheumatic drugs. She remains without
      articular symptoms for 7 years, and then she develops a Felty's syndrome
      requiring steroid treatment and splenectomy. Following steroid withdrawal she
      develops pericarditis with massive serohematic pericardial effusion, still in
      absence of articular activity, and responds to immunosuppressive therapy and
      colchicine. We emphasize the unusual spontaneous and sustained joint remission
      without specific treatment, and the development of severe extra-articular
      manifestations of RA in absence of concomitant articular activity, as well as the
      importance of controlling inflammation. 

PMID- 26316107
TI  - Quantitative gene set analysis generalized for repeated measures, confounder
      adjustment, and continuous covariates.
AB  - BACKGROUND: Gene set analysis (GSA) of gene expression data can be highly
      powerful when the biological signal is weak compared to other sources of
      variability in the data. However, many gene set analysis approaches utilize
      permutation tests which are not appropriate for complex study designs. For
      example, the correlation of subjects is broken when comparing time points within
      a longitudinal study. Linear mixed models provide a method to analyze
      longitudinal studies as well as adjust for potential confounding factors and
      account for sources of variability that are not of primary interest. Currently,
      there are no known gene set analysis approaches that fully account for these
      study design and analysis aspects. In order to do so, we generalize the QuSAGE
      gene set analysis algorithm, denoted Q-Gen, and provide the necessary estimation
      adjustments to incorporate linear mixed model analyses. RESULTS: We assessed the
      performance of our generalized method in comparison to the original QuSAGE method
      in settings such as longitudinal repeated measures analysis and accounting for
      potential confounders. We demonstrate that the original QuSAGE method can not
      control for type-I error when these complexities exist. In addition to
      statistical appropriateness, analysis of a longitudinal influenza study suggests
      Q-Gen can allow for greater sensitivity when exploring a large number of gene
      sets. CONCLUSIONS: Q-Gen is an extension to the gene set analysis method of
      QuSAGE, and allows for linear mixed models to be applied appropriately within a
      gene set analysis framework. It provides GSA an added layer of flexibility that
      was not currently available. This flexibility allows for more appropriate
      statistical modeling of complex data structures that are inherent to many
      microarray study designs and can provide more sensitivity.

PMID- 26316108
TI  - Interacting Network of the Gap Junction (GJ) Protein Connexin43 (Cx43) is
      Modulated by Ischemia and Reperfusion in the Heart.
AB  - The coordinated and synchronized cardiac muscle contraction relies on an
      efficient gap junction-mediated intercellular communication (GJIC) between
      cardiomyocytes, which involves the rapid anisotropic impulse propagation through
      connexin (Cx)-containing channels, namely of Cx43, the most abundant Cx in the
      heart. Expectedly, disturbing mechanisms that affect channel activity,
      localization and turnover of Cx43 have been implicated in several
      cardiomyopathies, such as myocardial ischemia. Besides gap junction-mediated
      intercellular communication, Cx43 has been associated with channel-independent
      functions, including modulation of cell adhesion, differentiation, proliferation
      and gene transcription. It has been suggested that the role played by Cx43 is
      dictated by the nature of the proteins that interact with Cx43. Therefore, the
      characterization of the Cx43-interacting network and its dynamics is vital to
      understand not only the molecular mechanisms underlying pathological malfunction
      of gap junction-mediated intercellular communication, but also to unveil novel
      and unanticipated biological functions of Cx43. In the present report, we applied
      a quantitative SWATH-MS approach to characterize the Cx43 interactome in rat
      hearts subjected to ischemia and ischemia-reperfusion. Our results demonstrate
      that, in the heart, Cx43 interacts with proteins related with various biological
      processes such as metabolism, signaling and trafficking. The interaction of Cx43
      with proteins involved in gene transcription strengthens the emerging concept
      that Cx43 has a role in gene expression regulation. Importantly, our data shows
      that the interactome of Cx43 (Connexome) is differentially modulated in diseased
      hearts. Overall, the characterization of Cx43-interacting network may contribute
      to the establishment of new therapeutic targets to modulate cardiac function in
      physiological and pathological conditions. Data are available via ProteomeXchange
      with identifier PXD002331. 

PMID- 26316109
TI  - Surgeons OverSeas Assessment of Surgical Need (SOSAS) Uganda: Update for
      Household Survey.
AB  - INTRODUCTION: The first step in improving surgical care delivery in low- and
      middle-income countries (LMICs) is quantifying surgical need. The Surgeons
      OverSeas Assessment of Surgical Need (SOSAS) is a validated household survey that
      has been previously implemented in three LMICs with great success. We implemented
      the SOSAS survey in Uganda, a medium-sized country with comparatively more
      language and ethnic group diversity. METHODS: The investigators partnered with
      the Performance Monitoring and Accountability 2020 (PMA2020) Uganda to access a
      data collection platform sampling 2520 households in 105 randomly selected
      enumeration areas. Due to geographic size consideration and language diversity,
      SOSAS's methodology was updated in three significant dimensions (1) technology,
      (2) staff management, and (3) questionnaire adaptations. RESULTS: The SOSAS
      survey was successfully implemented with non-medically trained but field proven
      research assistants. We sampled 2315 of 2402 eligible households (response rate
      96.4 %) and 4248 of 4374 eligible individual respondents (response rate 97.1 %).
      The female-to-male ratio was 51.1-48.9 %. Total survey cost was USD 73,145 and
      data collection occurred in 14 days. DISCUSSION: SOSAS Uganda has demonstrated
      that non-medically trained, but university-educated, experienced researchers
      supervised by academic surgeons can successfully perform accurate data collection
      of SOSAS. SOSAS can be successfully implemented within larger and more diverse
      LMICs using existing national survey platforms, and SOSAS Uganda provides
      insights on how SOSAS can be executed specifically within other PMA2020 program
      countries.

PMID- 26316110
TI  - Feasibility of Catheter Placement Under Ultrasound Guidance for Progressive
      Preoperative Pneumoperitoneum for Large Incisional Hernia with Loss of Domain.
AB  - INTRODUCTION: Large incisional hernias with loss of domain (LIHLD) of the
      abdominal wall remain a therapeutic challenge due to the difficulty of replacing
      the contents of the hernia sac into the peritoneal cavity. Preoperative
      progressive pneumoperitoneum (PPP) is a valuable option. The purpose of this
      study was to evaluate the feasibility of peritoneal catheter insertion under
      ultrasound guidance for PPP and to compare the morbidity and mortality of this
      new technique to previously used techniques in our department. METHODS: Medical
      records were reviewed retrospectively from February 1989 to April 2013 in a
      single institution. Three different techniques of PPP were evaluated: surgical
      subcutaneous implantable port (SIP), surgical peritoneal dialysis catheter (PDC),
      and radiologic multipurpose drainage catheter (MDC). Collected data included
      patients' age, sex, body mass index, medical and surgical history, hernia
      location, PPP technique, length of hospitalization, volume of air injected,
      morbidity and mortality linked to PPP, and the procedure of hernia repair.
      RESULTS: Thirty-seven patients with a mean age of 63.1 years were evaluated.
      Progressive preoperative pneumoperitoneum was performed using SIP, PDC, and MDC
      for 14, 11, and 12 patients, respectively. Overall morbidity related to the
      technique was seen in 36 % of SIP, 27 % of PDC, and 0 % of MDC. One patient from
      the SIP group died on the 3rd postoperative day due to septic shock following
      aspiration pneumonia. No postoperative mortality in the other groups was
      observed. CONCLUSION: The MDC is an interesting modification of the original
      technique and is a safe procedure. It is a minimally invasive technique with a
      very low risk of perforation of the viscera. Therefore, the use of a non
      absorbable prosthesis with MDC technique can be offered for all patients
      undergoing PPP without increasing the risk of infection.

PMID- 26316111
TI  - A Comparison of Laparoscopy and Laparotomy for the Management of Abdominal
      Trauma: A Systematic Review and Meta-analysis.
AB  - BACKGROUND: This study aimed to systematically review and compare the
      perioperative outcomes of laparoscopy with laparotomy for abdominal trauma
      patients. METHODS: We conducted a systematic review and meta-analysis comparing
      the perioperative outcomes of laparoscopy with laparotomy for abdominal trauma
      patients. Clinical endpoints included length of hospital stay, operation time,
      amount of intraoperative blood loss, time to postoperative exhaust, time to
      regular diet, time to out of bed, duration of postoperative pain, postoperative
      complications, perioperative mortality rate, length of intensive care unit (ICU)
      stay, missed injuries, conversions to laparotomy, and cure rate. RESULTS: Sixty
      four studies including 9058 patients with abdominal trauma were included. In
      these studies, laparoscopy was used as a screening, diagnostic, or therapeutic
      tool. Meta-analysis showed significant reductions in the incidence of
      postoperative complications (relative risk [RR] [95 % confidence interval (CI)]
      0.37 [0.29-0.46]), perioperative mortality rate (RR 0.64; 95 % CI 0.52-0.80),
      operation time (mean difference [MD] [95 % CI] -19.93 min [-34.43 to 5.43]),
      length of hospital stay (MD -5.15 days; 95 % CI -6.80 to 3.50), amount of
      intraoperative blood loss (MD -141.33 ml; 95 % CI -260.99 to 21.67), time to
      postoperative exhaust (MD -5.32 h; 95 % CI -8.60 to 2.05), time to regular diet
      (MD -3.46 h; 95 % CI -6.31 to 0.61), time to out of bed (MD -23.51 h; 95 % CI 
      24.85 to 22.16), duration of postoperative pain (MD -21.34 h; 95 % CI -22.65 to
      20.03), length of ICU stay (MD -1.89 days; 95 % CI -4.05 to 0.27) in patients
      with abdominal trauma treated with laparoscopy compared with laparotomy. The
      pooled incidence of postoperative complications, missed injuries, conversions,
      and perioperative mortality rate of laparoscopy among the case reports were 0.04
      (95 % CI 0.03-0.06), 0.01 (95 % CI 0.01-0.02), 0.24 (95 % CI 0.20-0.28), 0.01(95
      % CI 0.01-0.02), respectively. Cure rate of laparoscopy ranged from 46 to 95 %
      and the pooled rate was 0.76 (95 % CI 0.71-0.81). CONCLUSIONS: Laparoscopy is an
      effective way to improve perioperative outcomes and reduce the complications of
      hemodynamically stable patients with abdominal trauma. It is worth further
      popularization in clinical practice.

PMID- 26316113
TI  - Incidence of Venous Thromboembolism Following Laparoscopic Surgery for
      Gastrointestinal Cancer: A Single-Center, Prospective Cohort Study.
AB  - BACKGROUND: The occurrence of venous thromboembolism (VTE), manifesting as deep
      vein thrombosis or pulmonary embolism, after gastric and colorectal cancer
      surgery remains poorly characterized. The purpose of this study was to
      investigate the incidence of VTE following laparoscopic surgery in Japanese
      patients with gastric and colorectal cancer and identify the associated risk
      factors. METHODS: We prospectively analyzed VTE events after laparoscopic surgery
      for gastric and colorectal cancer from April 2012 to March 2013 in our institute.
      Deep vein thrombosis was diagnosed with Doppler ultrasound sonography of the
      lower limb. Thromboprophylaxis, graduated compression stockings, and intermittent
      pneumatic compression were used in all patients. Fondaparinux sodium was used in
      several patients. We examined all patients' plasma D-dimer levels throughout the
      perioperative period. RESULTS: In total, 101 patients were enrolled in this
      study; 71 who underwent laparoscopic surgery for gastrointestinal cancer were
      finally analyzed. Thirteen patients (18.3 %) developed asymptomatic VTE. There
      were no relationships between the development of VTE and perioperative factors
      such as cardiovascular disease, operation time, blood loss, postoperative
      complications, and fondaparinux administration. Neoadjuvant treatment
      (chemotherapy or chemoradiotherapy) was significantly associated with VTE (p <
      0.05). Plasma D-dimer levels were higher 7 days after surgery in patients with
      than without VTE, although the levels remained high after surgery in all
      patients. CONCLUSIONS: The incidence of VTE among Japanese patients who underwent
      laparoscopic surgery for gastrointestinal cancer was not low. In particular,
      clinicians should consider the higher risk of VTE in patients undergoing
      neoadjuvant therapy.

PMID- 26316114
TI  - Through the Looking Glass: Real-Time Video Using 'Smart' Technology Provides
      Enhanced Intraoperative Logistics.
AB  - INTRODUCTION: In the setting of increasingly complex medical therapies and
      limited physician resources, the recent emergence of 'smart' technology offers
      tremendous potential for improved logistics, efficiency, and communication
      between medical team members. In an effort to harness these capabilities, we
      sought to evaluate the utility of this technology in surgical practice through
      the employment of a wearable camera device during cardiothoracic organ recovery.
      METHODS: A single procurement surgeon was trained for use of an Explorer Edition
      Google Glass (Google Inc., Mountain View, CA) during the recovery process. Live
      video feed of each procedure was securely broadcast to allow for members of the
      home transplant team to remotely participate in organ assessment. Primary
      outcomes involved demonstration of technological feasibility and validation of
      quality assurance through group assessment. RESULTS: The device was employed for
      the recovery of four organs: a right single lung, a left single lung, and two
      bilateral lung harvests. Live video of the visualization process was remotely
      accessed by the home transplant team, and supplemented final verification of
      organ quality. In each case, the organs were accepted for transplant without
      disruption of standard procurement protocols. Media files generated during the
      procedures were stored in a secure drive for future documentation, evaluation,
      and education purposes without preservation of patient identifiers. CONCLUSIONS:
      Live video streaming can improve quality assurance measures by allowing off-site
      members of the transplant team to participate in the final assessment of donor
      organ quality. While further studies are needed, this project suggests that the
      application of mobile 'smart' technology offers not just immediate value, but the
      potential to transform our approach to the practice of medicine.

PMID- 26316112
TI  - Augmented Reality Guidance for the Resection of Missing Colorectal Liver
      Metastases: An Initial Experience.
AB  - BACKGROUND: Modern chemotherapy achieves the shrinking of colorectal cancer liver
      metastases (CRLM) to such extent that they may disappear from radiological
      imaging. Disappearing CRLM rarely represents a complete pathological remission
      and have an important risk of recurrence. Augmented reality (AR) consists in the
      fusion of real-time patient images with a computer-generated 3D virtual patient
      model created from pre-operative medical imaging. The aim of this prospective
      pilot study is to investigate the potential of AR navigation as a tool to help
      locate and surgically resect missing CRLM. METHODS: A 3D virtual anatomical model
      was created from thoracoabdominal CT-scans using customary software (VR
      RENDER((r)), IRCAD). The virtual model was superimposed to the operative field
      using an Exoscope (VITOM((r)), Karl Storz, Tuttlingen, Germany). Virtual and real
      images were manually registered in real-time using a video mixer, based on
      external anatomical landmarks with an estimated accuracy of 5 mm. This modality
      was tested in three patients, with four missing CRLM that had sizes from 12 to 24
      mm, undergoing laparotomy after receiving pre-operative oxaliplatin-based
      chemotherapy. RESULTS: AR display and fine registration was performed within 6
      min. AR helped detect all four missing CRLM, and guided their resection. In all
      cases the planned security margin of 1 cm was clear and resections were confirmed
      to be R0 by pathology. There was no postoperative major morbidity or mortality.
      No local recurrence occurred in the follow-up period of 6-22 months. CONCLUSIONS:
      This initial experience suggests that AR may be a helpful navigation tool for the
      resection of missing CRLM.

PMID- 26316115
TI  - Pure Laparoscopic Versus Open Left Lateral Sectionectomy for Hepatocellular
      Carcinoma: A Single-Center Experience.
AB  - INTRODUCTION: Laparoscopic left lateral sectionectomy has been proven to be a
      safe and effective treatment for liver lesions. However, most of the literatures
      only reported this treatment method on benign lesion or colorectal metastases.
      The data on long-term outcome of laparoscopic left lateral section resection in
      patients with HCC and cirrhosis are still limited. The aim of this study is to
      analyze the survival outcome of laparoscopic left lateral sectionectomy when
      compared to open approach in patients with HCCs. METHOD: Between January 2004 and
      September 2014, 967 patients had primary HCC with hepatectomy performed. Twenty
      four patients had undergone pure laparoscopic left lateral sectionectomy for
      hepatocellular carcinoma (HCC). Twenty-nine patients with case-matched tumor
      characteristics and liver functions but received open left lateral sectionectomy
      for HCC were included for comparison. RESULTS: Comparing laparoscopic group to
      open resection group, the median operation time was 190.5 versus 195 min (P =
      0.734); the median blood loss was 100 versus 300 ml (P < 0.001). Hospital stay
      was 5 days in laparoscopic group versus 6 days in the open group (P = 0.057).
      There was no difference between the two groups in terms of complications (P =
      0.495). The median survival in laparoscopic group was >115 months versus >125
      months in the open group (P = 0.853). CONCLUSION: Laparoscopic left lateral
      sectionectomy for HCC is a safe and simple procedure associated with less blood
      loss. The survival outcome is comparable with conventional open approach. It is
      becoming a more favorable treatment option even for patients with HCC and
      cirrhosis.

PMID- 26316116
TI  - Liver Resection for De Novo Hepatocellular Carcinoma Complicated by Pyogenic
      Liver Abscess: A Clinical Challenge.
AB  - BACKGROUND: De novo hepatocellular carcinoma (HCC) complicated by pyogenic liver
      abscess is rare, and the standard of care for this disease has yet been defined.
      This study assesses whether liver resection can be recommended as its standard
      treatment. METHODS: This retrospective study reviewed the prospectively collected
      data of the 1725 patients who underwent primary liver resection for HCC at our
      hospital during the period from December 1989 to December 2012. Outcomes were
      compared between patients with and without liver abscess. RESULTS: Twenty-two
      (1.28 %) patients had HCC and liver abscess. Fourteen of them received
      preoperative drainage. Patients with and without abscess had similar tumor
      characteristics, but patients with abscess had more operative blood loss (2.2 vs.
      0.8 L; p < 0.0001) and more of them needed blood transfusion (63.6 vs. 23.1 %; p
      < 0.0001). They also had a longer hospital stay (38.5 vs. 10 days; p < 0.0001), a
      higher hospital mortality (40.9 vs. 2.8 %; p < 0.001), a higher postoperative
      complication rate (100 vs. 25.9 %; p < 0.0001), and poorer 1, 3, and 5-years
      disease-free survival rates (p = 0.023). CONCLUSIONS: The post-resection
      mortality of the patients with de novo HCC complicated by pyogenic liver abscess
      was so high that liver resection is not recommended as the standard treatment.
      More research is needed to determine the best therapy for this rare disease.

PMID- 26316117
TI  - Downregulation of miR-138 as a Contributing Mechanism to Lcn-2 Overexpression in
      Colorectal Cancer with Liver Metastasis.

PMID- 26316118
TI  - Papillary Thyroid Microcarcinoma: An Over-Treated Malignancy?

PMID- 26316119
TI  - Juvenile Idiopathic Arthritis in Olmsted County, Minnesota, 1960-2013.
AB  - OBJECTIVE: To evaluate the incidence and prevalence of juvenile idiopathic
      arthritis (JIA) in Olmsted County, Minnesota in 1994-2013 and trends in juvenile
      rheumatoid arthritis (JRA) in 1960-2013. METHODS: Cases of arthritis in 1994-2013
      were identified by diagnosis code with medical chart review to confirm diagnosis
      separately for JIA and JRA. Overall incidence rates with 95% confidence intervals
      (95% CIs) were age and sex adjusted to the 2010 US white population. Comparisons
      were made with an earlier (1960-1993) cohort from this same population. RESULTS:
      Seventy-one incident cases of JIA in 1994-2013 were identified, with an overall
      age- and sex-adjusted incidence rate of 10.3 per 100,000 (95% CI 7.9-12.7). Forty
      two (59%) were female, with an incidence of 12.4 per 100,000 (95% CI 8.6-16.2),
      as compared to 8.3 per 100,000 (95% CI 5.2-11.3) in males. The most common
      subtype was oligoarthritis (63%). The mean +/- SD age at diagnosis was 8.2 +/-
      5.3 years. The prevalence of JIA on January 1, 2000 and January 1, 2010 was 51.0
      per 100,000 (95% CI 25.2-76.8) and 57.6 per 100,000 (95% CI 31.0-94.5),
      respectively. When the annual incidence of JRA was compared over time from 1960
      to 2013, there was no significant change in incidence overall; however, the
      incidence decreased among females (P = 0.003). A cyclic pattern of incidence was
      observed, with peaks approximately every 10 years. Similar to the findings with
      regard to incidence, prevalence did not change overall, but decreased among
      females (P = 0.048). There were 4 deaths in the cohort of JRA patients diagnosed
      in 1960-2013; the standardized mortality ratio was 1.50 (95% CI 0.41-3.83).
      CONCLUSION: Incidence of juvenile arthritis overall in Olmsted County, Minnesota
      has not changed significantly in the past 53 years. A consistent cyclic pattern
      was noted.

PMID- 26316121
TI  - 'Response to Midwifery students' experiences of an innovative clinical placement
      model embedded within midwifery continuity of care in Australia'.

PMID- 26316120
TI  - Solution structure of the transmembrane domain of the mouse erythropoietin
      receptor in detergent micelles.
AB  - Erythropoiesis is regulated by the erythropoietin receptor (EpoR) binding to its
      ligand. The transmembrane domain (TMD) and the juxtamembrane (JM) regions of the
      EpoR are important for signal transduction across the cell membrane. We report a
      solution NMR study of the mouse erythropoietin receptor (mEpoR) comprising the
      TMD and the JM regions reconstituted in dodecylphosphocholine (DPC) micelles. The
      TMD and the C-terminal JM region of the mEpoR are mainly alpha-helical, adopting
      a similar structure to those of the human EpoR. Residues from S216 to T219 in
      mEpoR form a short helix. Relaxation study demonstrates that the TMD of the mEpoR
      is rigid whilst the N-terminal region preceding the TMD is flexible. Fluorescence
      spectroscopy and sequence analysis indicate that the C-terminal JM region is
      exposed to the solvent. Helix wheel result shows that there is hydrophilic patch
      in the TMD of the mEpoR formed by residues S231, S238 and T242, and these
      residues might be important for the receptor dimerization. 

PMID- 26316122
TI  - Gene expression signatures of breast cancer stem and progenitor cells do not
      exhibit features of Warburg metabolism.
AB  - INTRODUCTION: Cancers are believed to adapt to continual changes in glucose and
      oxygen availability by relying almost exclusively on glycolytic metabolism for
      energy (i.e. the Warburg effect). The process by which breast cancers sustain
      growth in avascular tissue is thought to be mediated via aberrant hypoxia
      response with ensuing shifts in glycolytic metabolism. Given their role in
      initiating and perpetuating tumors, we sought to determine whether breast cancer
      stem and progenitor cells play an instrumental role in this adaptive metabolic
      response. METHODS: Breast cancer stem/progenitor cells were isolated from
      invasive ductal carcinomas, and benign stem cells (SC) were isolated from
      reduction mammoplasty tissues. Relative expression of 33 genes involved in
      hypoxia and glucose metabolism was evaluated in flow cytometrically isolated stem
      and progenitor cell populations. Significance between cohorts and cell
      populations was determined using Student's 2-tailed t test. RESULTS: While benign
      stem/progenitor cells exhibited few significant inter-group differences in
      expression of genes involved in hypoxia regulation or glucose metabolism, breast
      cancer stem/progenitor cells demonstrated significant inter-group variability.
      Breast cancer stem/progenitor cells adapted to microenvironments through changes
      in stem cell numbers and transcription of glycolytic genes. One of four breast
      cancer stem/progenitor cells subpopulations exhibited an aerobic glycolysis gene
      expression signature. This subpopulation comprises the majority of the tumor and
      therefore best reflects invasive ductal carcinoma tumor biology. Although
      PI3K/AKT mutations are associated with increased proliferation of breast cancer
      cells, mutations in breast cancer stem/progenitor cells subpopulations did not
      correlate with changes in metabolic gene expression. CONCLUSIONS: The adaptive
      capacity of breast cancer stem/progenitor cells may enable tumors to survive
      variable conditions encountered during progressive stages of cancer growth.

PMID- 26316124
TI  - Dot-Diffused Halftoning With Improved Homogeneity.
AB  - Compared with the error diffusion, dot diffusion provides an additional pixel
      level parallelism for digital halftoning. However, even though its periodic and
      blocking artifacts had been eased by the previous works, it was still far from
      satisfactory in terms of the blue noise spectrum perspective. In this paper, we
      strengthen the relation among the pixel locations of the same processing order by
      an iterative halftoning method, and the results demonstrate a significant
      improvement. Moreover, a new approach of deriving the averaged power spectrum
      density is proposed to avoid the regular sampling of the well-known Bartlett's
      procedure which inaccurately presents the halftone periodicity of certain
      halftoning techniques with parallelism. As a result, the proposed dot diffusion
      is substantially superior to the state-of-the-art parallel halftoning methods in
      terms of visual quality and artifact-free property, and competitive runtime to
      the theoretical fastest ordered dithering is offered simultaneously. 

PMID- 26316123
TI  - Dichotic Listening Can Improve Perceived Clarity of Music in Cochlear Implant
      Users.
AB  - Musical enjoyment for cochlear implant (CI) recipients is often reported to be
      unsatisfactory. Our goal was to determine whether the musical experience of
      postlingually deafened adult CI recipients could be enriched by presenting the
      bass and treble clef parts of short polyphonic piano pieces separately to each
      ear (dichotic). Dichotic presentation should artificially enhance the
      lateralization cues of each part and help the listeners to better segregate them
      and thus provide greater clarity. We also hypothesized that perception of the
      intended emotion of the pieces and their overall enjoyment would be enhanced in
      the dichotic mode compared with the monophonic (both parts in the same ear) and
      the diotic mode (both parts in both ears). Twenty-eight piano pieces specifically
      composed to induce sad or happy emotions were selected. The tempo of the pieces,
      which ranged from lento to presto covaried with the intended emotion (from sad to
      happy). Thirty participants (11 normal-hearing listeners, 11 bimodal CI and
      hearing-aid users, and 8 bilaterally implanted CI users) participated in this
      study. Participants were asked to rate the perceived clarity, the intended
      emotion, and their preference of each piece in different listening modes. Results
      indicated that dichotic presentation produced small significant improvements in
      subjective ratings based on perceived clarity and preference. We also found that
      preference and clarity ratings were significantly higher for pieces with fast
      tempi compared with slow tempi. However, no significant differences between
      diotic and dichotic presentation were found for the participants' preference
      ratings, or their judgments of intended emotion. 

PMID- 26316125
TI  - Dual Graph Regularized Latent Low-Rank Representation for Subspace Clustering.
AB  - Low-rank representation (LRR) has received considerable attention in subspace
      segmentation due to its effectiveness in exploring low-dimensional subspace
      structures embedded in data. To preserve the intrinsic geometrical structure of
      data, a graph regularizer has been introduced into LRR framework for learning the
      locality and similarity information within data. However, it is often the case
      that not only the high-dimensional data reside on a non-linear low-dimensional
      manifold in the ambient space, but also their features lie on a manifold in
      feature space. In this paper, we propose a dual graph regularized LRR model
      (DGLRR) by enforcing preservation of geometric information in both the ambient
      space and the feature space. The proposed method aims for simultaneously
      considering the geometric structures of the data manifold and the feature
      manifold. Furthermore, we extend the DGLRR model to include non-negative
      constraint, leading to a parts-based representation of data. Experiments are
      conducted on several image data sets to demonstrate that the proposed method
      outperforms the state-of-the-art approaches in image clustering. 

PMID- 26316126
TI  - Joint Group Sparse PCA for Compressed Hyperspectral Imaging.
AB  - A sparse principal component analysis (PCA) seeks a sparse linear combination of
      input features (variables), so that the derived features still explain most of
      the variations in the data. A group sparse PCA introduces structural constraints
      on the features in seeking such a linear combination. Collectively, the derived
      principal components may still require measuring all the input features. We
      present a joint group sparse PCA (JGSPCA) algorithm, which forces the basic
      coefficients corresponding to a group of features to be jointly sparse. Joint
      sparsity ensures that the complete basis involves only a sparse set of input
      features, whereas the group sparsity ensures that the structural integrity of the
      features is maximally preserved. We evaluate the JGSPCA algorithm on the problems
      of compressed hyperspectral imaging and face recognition. Compressed sensing
      results show that the proposed method consistently outperforms sparse PCA and
      group sparse PCA in reconstructing the hyperspectral scenes of natural and man
      made objects. The efficacy of the proposed compressed sensing method is further
      demonstrated in band selection for face recognition. 

PMID- 26316127
TI  - 2D Non-Separable Block-Lifting Structure and Its Application to M-Channel Perfect
      Reconstruction Filter Banks for Lossy-to-Lossless Image Coding.
AB  - We propose a 2D non-separable block-lifting structure (2D-NSBL) that is easily
      formulated from the 1D separable block-lifting structure (1D-SBL) and 2D non
      separable lifting structure (2D-NSL). The 2D-NSBL can be regarded as an extension
      of the 2D-NSL, because a two-channel 2D-NSBL is completely equivalent to a 2D
      NSL. We apply the 2D-NSBL to M-channel ( M=2(n), n ? N) perfect reconstruction
      filter banks (PRFBs). The 2D-NSBL-based PRFBs outperform 1D-SBL-based PRFBs at
      lossy-to-lossless coding, whose image quality is scalable from lossless data to
      high compressed lossy data, because their rounding errors are reduced by merging
      many rounding operations.

PMID- 26316128
TI  - Image Segmentation With Cage Active Contours.
AB  - In this paper, we present a framework for image segmentation based on
      parametrized active contours. The evolving contour is parametrized according to a
      reduced set of control points that form a closed polygon and have a clear visual
      interpretation. The parametrization, called mean value coordinates, stems from
      the techniques used in computer graphics to animate virtual models. Our framework
      allows to easily formulate region-based energies to segment an image. In
      particular, we present three different local region-based energy terms: 1) the
      mean model; 2) the Gaussian model; 3) and the histogram model. We show the
      behavior of our method on synthetic and real images and compare the performance
      with state-of-the-art level set methods. 

PMID- 26316129
TI  - Image-Specific Prior Adaptation for Denoising.
AB  - Image priors are essential to many image restoration applications, including
      denoising, deblurring, and inpainting. Existing methods use either priors from
      the given image (internal) or priors from a separate collection of images
      (external). We find through statistical analysis that unifying the internal and
      external patch priors may yield a better patch prior. We propose a novel prior
      learning algorithm that combines the strength of both internal and external
      priors. In particular, we first learn a generic Gaussian mixture model from a
      collection of training images and then adapt the model to the given image by
      simultaneously adding additional components and refining the component
      parameters. We apply this image-specific prior to image denoising. The
      experimental results show that our approach yields better or competitive
      denoising results in terms of both the peak signal-to-noise ratio and structural
      similarity. 

PMID- 26316130
TI  - Visual Quality Evaluation of Image Object Segmentation: Subjective Assessment and
      Objective Measure.
AB  - A visual quality evaluation of image object segmentation as one member of the
      visual quality evaluation family has been studied over the years. Researchers aim
      at developing the objective measures that can evaluate the visual quality of
      object segmentation results in agreement with human quality judgments. It is also
      significant to construct a platform for evaluating the performance of the
      objective measures in order to analyze their pros and cons. In this paper, first,
      we present a novel subjective object segmentation visual quality database, in
      which a total of 255 segmentation results were evaluated by more than thirty
      human subjects. Then, we propose a novel full-reference objective measure for an
      object segmentation visual quality evaluation, which involves four human visual
      properties. Finally, our measure is compared with some state-of-the-art objective
      measures on our database. The experiment demonstrates that the proposed measure
      performs better in matching subjective judgments. Moreover, the database is
      available publicly for other researchers in the field to evaluate their measures.

PMID- 26316131
TI  - Stroke Detector and Structure Based Models for Character Recognition: A
      Comparative Study.
AB  - Characters, which are man-made symbols composed of strokes arranged in a certain
      structure, could provide semantic information and play an indispensable role in
      our daily life. In this paper, we try to make use of the intrinsic
      characteristics of characters and explore the stroke and structure-based methods
      for character recognition. First, we introduce two existing part-based models to
      recognize characters by detecting the elastic strokelike parts. In order to
      utilize strokes of various scales, we propose to learn the discriminative multi
      scale stroke detector-based representation (DMSDR) for characters. However, the
      part-based models and DMSDR need to manually label the parts or key points for
      training. In order to learn the discriminative stroke detectors automatically, we
      further propose the discriminative spatiality embedded dictionary learning-based
      representation (DSEDR) for character recognition. We make a comparative study of
      the performance of the tree-structured model (TSM), mixtures-of-parts TSM, DMSDR,
      and DSEDR for character recognition on three challenging scene character
      recognition (SCR) data sets as well as two handwritten digits recognition data
      sets. A series of experiments is done on these data sets with various
      experimental setup. The experimental results demonstrate the suitability of
      stroke detector-based models for recognizing characters with deformations and
      distortions, especially in the case of limited training samples. 

PMID- 26316132
TI  - PET-CT in the sub-arctic region of Norway 2010-2013. At the edge of what is
      possible?
AB  - BACKGROUND: It is challenging to obtain a similar access to positron emission
      tomography/computed tomography (PET-CT) within the whole region served. In the
      subarctic and arctic region of Norway, significant distances, weather conditions
      and seasonable darkness have been challenging when the health care provider has
      aimed for a high quality PET-CT service with similar availability to all
      inhabitants. METHODS: The PET-CT service at the University Hospital of North
      Norway (UNN) was established in May 2010. The glucose analogue tracer fluorine-18
      fluorodeoxyglucose (FDG) was delivered from Helsinki, Finland. An ambulatory PET
      CT scanner was initially employed and a permanent local one was introduced in
      October 2011. In March 2014, we analysed retrospectively all data on the PET-CT
      exams performed at the Section of Nuclear Medicine, Department of Radiology
      during a 32 months time period 2010-13. The following patient data were recorded:
      gender, age, diagnosis, residence and distance of travelling. There were in total
      796 exams in 706 patients. RESULTS: Four hundred sixty-one PET-CT exams per
      million inhabitants were, on average, performed per year. Lung cancer (32.7%),
      malignant melanoma (11.3%), colorectal cancer (10.9%) and lymphoma (9.7%)
      constituted two-thirds of all exams. Three-fourths were males and the median age
      was 63.5 years (range 15.2-91.4 years). The access to PET-CT exam varied within
      the region. The southern county (Nordland) experienced a significantly less
      access (p < 0.0001) to the regional service. Except for malignant melanoma, this
      finding was observed in all major cancer subgroups. In colorectal cancer and
      lymphoma a lower consumption of PET-CT was also observed in the northeastern
      county (Finnmark). Patients' mean distance of travelling by car (one way) was 373
      km (median 313 km, range 5-936 km). CONCLUSION: PET-CT was not similarly
      available within the region. Especially, inhabitants in the southern county
      experienced less access to the regional service. National and regional standards
      of care, new scanners and improved collaboration between hospital trusts may
      alter this situation.

PMID- 26316134
TI  - Audiometric Results after Stapedotomy Operations in Patients with Otosclerosis
      and Preoperative Small Air-Bone Gaps.
AB  - OBJECTIVES: The efficacy of stapedotomies performed on patients with small air
      bone gaps (<25 dB) was compared with the efficacy of the operation in patients
      who had otosclerosis with high air-bone gaps (>=25 dB). METHODS: This
      retrospective study evaluates the short-term postoperative air and bone
      conduction thresholds and air-bone gaps after 182 CO2 laser stapedotomies.
      RESULTS: A significantly smaller air-bone gap and lower air conduction thresholds
      after surgery were observed in the group of patients who underwent surgery with
      preoperative air-bone gaps of less than 25 dB. Bone conduction thresholds improve
      in the group with small air-bone gaps after surgery. CONCLUSIONS: The results
      after stapedotomies are good even if the preoperative air-bone gap is small and
      the overall risk of hearing deterioration due to stapes surgery remains low.

PMID- 26316133
TI  - International veterinary epilepsy task force consensus report on epilepsy
      definition, classification and terminology in companion animals.
AB  - Dogs with epilepsy are among the commonest neurological patients in veterinary
      practice and therefore have historically attracted much attention with regard to
      definitions, clinical approach and management. A number of classification
      proposals for canine epilepsy have been published during the years reflecting
      always in parts the current proposals coming from the human epilepsy organisation
      the International League Against Epilepsy (ILAE). It has however not been
      possible to gain agreed consensus, "a common language", for the classification
      and terminology used between veterinary and human neurologists and
      neuroscientists, practitioners, neuropharmacologists and neuropathologists. This
      has led to an unfortunate situation where different veterinary publications and
      textbook chapters on epilepsy merely reflect individual author preferences with
      respect to terminology, which can be confusing to the readers and influence the
      definition and diagnosis of epilepsy in first line practice and research
      studies.In this document the International Veterinary Epilepsy Task Force (IVETF)
      discusses current understanding of canine epilepsy and presents our 2015 proposal
      for terminology and classification of epilepsy and epileptic seizures. We propose
      a classification system which reflects new thoughts from the human ILAE but also
      roots in former well accepted terminology. We think that this classification
      system can be used by all stakeholders. 

PMID- 26316135
TI  - Vegetarianism, low meat consumption and the risk of colorectal cancer in a
      population based cohort study.
AB  - To study how a vegetarian or low meat diet influences the risk of colorectal
      cancer compared to a high meat diet, and to assess the explanatory role of
      factors associated with these diets. In the Netherlands Cohort Study - Meat
      Investigation Cohort (NLCS-MIC) (cohort of 10,210 individuals including 1040 self
      defined vegetarians), subjects completed a baseline questionnaire in 1986, based
      on which they were classified into vegetarians (n = 635), pescetarians (n = 360),
      1 day/week- (n = 1259), 2-5 day/week- (n = 2703), and 6-7 day/week meat consumers
      (n = 5253). After 20.3 years of follow-up, 437 colorectal cancer cases (307
      colon, 92 rectal) were available. A non-significantly decreased risk of CRC for
      vegetarians, pescetarians, and 1 day/week compared to 6-7 day/week meat consumers
      was observed (age/sex adjusted Hazard Ratios (HR): 0.73(0.47-1.13), 0.80(0.47
      1.39), and 0.72(0.52-1.00), respectively). Most of the differences in HR between
      these groups could be explained by intake of dietary fiber and soy products.
      Other (non-)dietary factors characteristic for a vegetarian or low meat diet had
      negligible individual effects, but attenuated the HRs towards the null when
      combined. Vegetarians, pescetarians, and 1 day/week meat eaters showed a non
      significantly decreased risk of colorectal cancer compared to 6-7 day/week meat
      consumers, mainly due to differences in dietary pattern other than meat intake. 

PMID- 26316136
TI  - Vascular Plug-Assisted Retrograde Transvenous Obliteration for the Treatment of
      Gastric Varices and Hepatic Encephalopathy: A Prospective Multicenter Study.
AB  - PURPOSE: To evaluate technical and clinical outcomes of vascular plug-assisted
      retrograde transvenous obliteration (PARTO) for the treatment of gastric varices
      (GVs) and hepatic encephalopathy (HE). MATERIALS AND METHODS: From March 2012 to
      June 2014, 73 consecutive patients (47 men, 26 women; mean age, 59 y; range, 28
      79 y) who had undergone PARTO were evaluated in a prospective multicenter study.
      Among 57 patients with GVs, 28 had GVs in danger of rupture, 23 had experienced
      recent bleeding, and 6 had active variceal bleeding. The 16 patients with HE had
      been treated unsuccessfully with medical therapies. RESULTS: Placement of the
      vascular plug and subsequent gelatin sponge embolization were technically
      successful in all 73 patients. There were no procedure-related complications.
      Follow-up CT obtained within 1 wk after PARTO showed complete thrombosis of GVs
      and portosystemic shunts in 72 of 73 patients (98.6%). Sixty patients who
      underwent follow-up longer than 3 mo showed complete obliteration of GVs and
      portosystemic shunts. There were no cases of variceal bleeding or HE at the end
      of follow-up (mean, 544 d). Improvement in Child-Pugh score was observed in 24
      patients (40%) at 1-mo follow-up. Worsening of ascites and esophageal varices was
      observed in 14 (23.3%) and 16 (26.7%) patients at 3-mo follow-up. CONCLUSIONS:
      The present results of PARTO indicate that it can be rapidly performed with high
      technical success and durable clinical efficacy for the treatment of GVs and HE
      in the presence of a portosystemic shunt. Therefore, PARTO might be considered a
      first-line treatment in appropriate patients.

PMID- 26316137
TI  - Randomized Trial Comparing Radiologic Pigtail Gastrostomy and Peroral Image
      Guided Gastrostomy: Intra- and Postprocedural Pain, Radiation Exposure,
      Complications, and Quality of Life.
AB  - PURPOSE: To prospectively compare radiologically created pigtail gastrostomy
      (PG), in which the tube is inserted directly through the abdominal wall, versus
      peroral image-guided gastrostomy (POG), in which the tube is inserted through the
      mouth. Pain profiles (primary outcome measure), fluoroscopy times, total room
      times, technical success, complications, and quality of life (QOL) were measured.
      MATERIALS AND METHODS: Sixty patients were prospectively randomized to receive 14
      F PG or 20-F POG tubes. All patients received prophylactically created
      gastrostomies before radiation therapy for head and neck squamous-cell carcinoma.
      Patients receiving palliative treatment were excluded, as were those with
      established pharyngeal obstruction. Pain was measured by numeric rating scale
      (NRS) scores for 6 weeks after the procedure and by intraprocedural fentanyl and
      midazolam doses and postprocedural 24-h morphine doses. Fluoroscopy times, total
      room times, technical success, complications up to 6 months, and gastrostomy
      related QOL (using the Functional Assessment of Cancer Therapy-Enteral Feeding
      questionnaire) were determined. RESULTS: Fifty-six patients underwent the
      randomized procedure. The POG group required significantly higher intraprocedural
      midazolam and fentanyl doses (mean, 1.2 mg and 67 MUg, respectively, for PG vs
      1.9 mg and 105 MUg for POG; P < .001) and had significantly longer fluoroscopy
      times (mean, 1.3 min for PG vs 4.8 min for POG; P < .0001). NRS scores, morphine
      doses, total room times, technical success, complication rates, and QOL did not
      differ significantly between groups. The one major complication, a misplaced PG
      in the peritoneal cavity, followed a technical failure of POG creation.
      CONCLUSIONS: Despite the differences in insertion technique and tube caliber, the
      measured outcomes of POG and PG are comparable.

PMID- 26316138
TI  - Reduction surgery using a combination of a stereolithographic model and
      navigation system for ossifying fibroma with secondary central giant cell
      granuloma.
AB  - Both central giant cell granuloma (CGCG) and ossifying fibroma (OF) are
      relatively common diseases. The synchronous presentation of CGCG and OF is,
      however, an extremely rare occurrence. We present an unusual case with the
      synchronous presentation of these two diseases in the maxilla and introduce a
      surgical strategy based on a combination of the stereolithographic model and
      navigation system for the treatment of gigantic OF with secondary CGCG. 

PMID- 26316139
TI  - Auditory-Perceptual and Acoustic Methods in Measuring Dysphonia Severity of
      Korean Speech.
AB  - OBJECTIVES: The purpose of this study was to explore the criterion-related
      concurrent validity of two standardized auditory-perceptual rating protocols and
      the Acoustic Voice Quality Index (AVQI) for measuring dysphonia severity in
      Korean speech. METHODS: Sixty native Korean subjects with various voice disorders
      were asked to sustain the vowel [a:] and to read aloud the Korean text "Walk." A
      3-second midvowel portion of the sustained vowel and two sentences (with 25
      syllables) were edited, concatenated, and analyzed according to methods described
      elsewhere. From 56 participants, both continuous speech and sustained vowel
      recordings had sufficiently high signal-to-noise ratios (35.5 dB and 37 dB on
      average, respectively) and were therefore subjected to further dysphonia severity
      analysis with (1) "G" or Grade from the GRBAS protocol, (2) "OS" or Overall
      Severity from the Consensus Auditory-Perceptual Evaluation of Voice protocol, and
      (3) AVQI. RESULTS: First, high correlations were found between G and OS (rS =
      0.955 for sustained vowels; rS = 0.965 for continuous speech). Second, the AVQI
      showed a strong correlation with G (rS = 0.911) as well as OS (rP = 0.924). These
      findings are in agreement with similar studies dealing with continuous speech in
      other languages. CONCLUSIONS: The present study highlights the criterion-related
      concurrent validity of these methods in Korean speech. Furthermore, it supports
      the cross-linguistic robustness of the AVQI as a valid and objective marker of
      overall dysphonia severity.

PMID- 26316140
TI  - Hybrid electrolytes with controlled network structures for lithium metal
      batteries.
AB  - Solid polymer electrolytes (SPEs) with tunable network structures are prepared by
      a facile one-pot reaction of polyhedral oligomeric silsesquioxane and
      poly(ethylene glycol). These SPEs, with high conductivity and high modulus,
      exhibit superior resistance to lithium dendrite growth even at high current
      densities. Measurements of lithium metal batteries with a LiFePO4 cathode show
      excellent cycling stability and rate capability. 

PMID- 26316141
TI  - Impaired CXCR1-dependent oxidative defence in active tuberculosis patients.
AB  - Much of the pronounced host inflammatory response that occurs in tuberculosis
      (TB) is related to failed immunity against the invading pathogen. The G-protein
      coupled receptors CXCR1 and CXCR2 are implicated in important signal transduction
      pathways in lung inflammatory responses. We investigated the expression and
      function of these receptors in a simple whole blood model from 24 patients with
      pulmonary TB and in subjects with latent TB infection (LTBI). Healthy controls
      were recruited from close contacts to the pulmonary index patients. We found that
      pulmonary TB patients had significantly increased CXCR1 expression on blood cells
      compared to LTBI subjects and controls (p < 0.001). In contrast, LTBI subjects
      had a significant increase in CXCR2 expression compared to pulmonary TB patients
      (p < 0.001) and controls (p < 0.01). Leukocyte function, measured as oxidative
      capacity, was decreased in pulmonary TB patients compared to LTBI and controls (p
      < 0.001) and correlated with the increased CXCR1 expression. Leukocyte
      recruitment, measured as the expression of microRNA-223 was increased in
      pulmonary TB patients compared to LTBI (p < 0.05). We found that variations in
      receptor expression are linked to disease progression and affect the immune
      response against Mycobacterium tuberculosis (Mtb). 

PMID- 26316142
TI  - Direct identification and discernment of Mycobacterium avium and Mycobacterium
      intracellulare using a real-time RNA isothermal amplification and detection
      method.
AB  - The purpose of this work was to establish a real-time simultaneous amplification
      and testing method for identification and discernment of Mycobacterium avium and
      Mycobacterium intracellulare (SAT-MAC assay) and to evaluate the efficiency with
      which this method can detect isolated strains and clinical sputum specimens. The
      specific 16S rRNA sequences of M. avium and M. intracellulare were used as
      targets to design RNA probes and a reverse transcription primer containing T7
      promoter. RNA isothermal amplification and real-time fluorescence detection were
      performed at 42  degrees C. SAT-MAC assay, culture tests on Lowenstein-Jensen (L
      J) culture medium and PCR-sequencing were used to test the clinical isolated
      strains and sputum specimens. The limit of detection (LOD) of M. avium and M.
      intracellulare by SAT-MAC was found to be 30 CFU/mL and 20 CFU/mL. SAT-MAC showed
      high specificity in 21 species of mycobacteria standard strains and 5 species of
      non-mycobacteria bacteria. Using PCR-sequencing as the reference method, both
      rates of SAT-MAC assay for identifying M. avium and M. intracellulare from
      clinical isolates were 100% (259/259). Consistent with the results of L-J culture
      combined PCR-sequencing, the coincidence rate of SAT-MAC assay in clinical sputum
      specimens was 100% (369/369) for M. avium and 99.19% (366/369) for Mycobacterium
      intracellular. The SAT-MAC assay can identify and distinguish M. avium and M.
      intracellulare rapidly and accurately. It may be suitable for use in clinical
      microbiology laboratories. 

PMID- 26316143
TI  - Predicting the carcass chemical composition and describing its growth in live
      pigs of different sexes using computed tomographys.
AB  - The aims of this study were (1) to evaluate the ability of computed tomography
      (CT) to predict the chemical composition of live pigs and carcasses, (2) to
      compare the chemical composition of four different sex types at a commercial
      slaughter weight and (3) to model and evaluate the chemical component growth of
      these sex types. A total of 92 pigs (24 entire males (EM), 24 surgically
      castrated males (CM), 20 immunocastrated males (IM) and 24 females (FE)) was
      used. A total of 48 pigs (12 per sex type) were scanned repeatedly in vivo using
      CT at 30, 70, 100 and 120 kg and slaughtered at the end of the experiment. The
      remaining 44 were CT scanned in vivo and slaughtered immediately: 12 pigs (4 EM,
      4 CM and 4 FE) at 30 kg and 16 pigs each at 70 kg and 100 kg (4 per sex type).
      The left carcasses were CT scanned, and the right carcasses were minced and
      analysed for protein, fat, moisture, ash, Ca and P content. Prediction equations
      for the chemical composition were developed using Partial Least Square
      regression. Allometric growth equations for the chemical components were
      modelled. By using live animal and carcass CT images, accurate prediction
      equations were obtained for the fat (with a root mean square error of prediction
      (RMSEPCV) of 1.31 and 1.34, respectively, and R 2=0.91 for both cases) and
      moisture relative content (g/100 g) (RMSEPCV=1.19 and 1.38 and R 2=0.94 and 0.93,
      respectively) and were less accurate for the protein (RMSEPCV=0.65 and 0.67 and R
      2=0.54 and 0.63, respectively) and mineral content (RMSEPCV from 0.28 to 1.83 and
      R 2 from 0.09 to 0.62). Better equations were developed for the absolute amounts
      of protein, fat, moisture and ash (kg) (RMSEPCV from 0.26 to 1.14 and R 2 from
      0.91 to 0.99) as well as Ca and P (g) (RMSEPCV=144 and 71, and R 2=0.76 to 0.66,
      respectively). At 120 kg, CM had a higher fat and lower moisture content than EM.
      For protein, CM and IM had lower values than FE and EM. The ash content was
      higher in EM and IM than in FE and CM, while IM had a higher Ca and P content
      than the others. The castrated animals showed a higher allometric coefficient for
      fat and a lower one for moisture, with IM having intermediate values. However,
      for the Ca and P models, IM presented higher coefficients than EM and FE, and CM
      were intermediate. 

PMID- 26316144
TI  - Age of entitlement and the young: Implications for social psychiatry.

PMID- 26316145
TI  - Association between helicobacter pylori infection and carcinoma of the larynx or
      pharynx.
AB  - BACKGROUND: Infection with Helicobacter pylori (H. pylori) plays a role in the
      development of gastric carcinoma. However, there is controversy as to whether H.
      pylori infection increases laryngeal or pharyngeal cancers. METHODS: We managed a
      systematic review of researches related to H. pylori infection in laryngeal or
      pharyngeal carcinomas, distributed up to December 2014. Odds ratios (ORs) and 95%
      confidence intervals (CIs) were assessed by random effects models or according to
      heterogeneity I(2) . RESULTS: Eleven studies were involved in the meta-analysis.
      Overall, H. pylori infection was significantly higher in the study group compared
      with the normal control group (OR = 2.87; 95% CI = 1.71-4.84; I(2) = 67.1; p <
      .0001, random effects analysis). The ORs for laryngeal carcinoma were 3.28 (95%
      CI = 1.91-5.63; I(2) = 58; p < .0001, random effects model). The ORs for
      pharyngeal cancer were 1.35 (95% CI = 0.86-2.12; p = .188, random effects model).
      CONCLUSION: This study supported the proposition that infection with H. pylori
      was related to laryngeal carcinoma, specifically in the hospital-based control
      group and diagnosed by polymerase chain reaction (PCR) or enzyme-linked
      immunosorbent assay (ELISA). Nevertheless, no significant relationship was
      discovered between H. pylori infection and pharyngeal cancer. (c) 2015 Wiley
      Periodicals, Inc. Head Neck 38: E2291-E2296, 2016.

PMID- 26316147
TI  - Visually guided pulmonary vein isolation in patients with persistent atrial
      fibrillation.
AB  - AIMS: The role of balloon catheters in patients with persistent forms of atrial
      fibrillation (AF) remains ill defined. We therefore sought to assess the safety
      and efficacy of a laser balloon (LB)-guided pulmonary vein isolation (PVI) in
      consecutive all-comers with persistent AF. METHODS AND RESULTS: All patients
      undergoing an LB-guided PVI procedure for persistent AF between January 2011 and
      December 2012 were matched to patients undergoing circumferential PVI using
      irrigated radiofrequency (RF) current ablation for date of procedure, age,
      gender, AF duration, left atrial (LA) size, and left ventricular ejection
      fraction. The primary endpoint was freedom from AF between 90 and 365 days post
      ablation after a single procedure. Eighty patients (mean age 66 +/- 9; 71% male)
      with a median (Q1-Q3) AF episode duration of 2 (1-3) months underwent successful
      PVI in the two groups. The primary endpoint of 1-year single procedure AF/atrial
      tachycardia (AT) recurrences was reached by 11/40 (27.5%) patients in the LB
      group and in 9/40 (22.5%) patients in the RF group (P = 0.87). During a mean
      follow-up of 517 +/- 170 days, 13 (32.5%) and 16 (40%) patients in the LB and RF
      groups, respectively, experienced AF/AT recurrences (P = 0.64). Procedural
      complications occurred in one patient in the LB group and in six patients in the
      RF group. CONCLUSION: A subset of patients with drug-refractory persistent AF of
      short duration benefit from pure PVI without additional substrate modification. A
      LB-based strategy showed similar outcomes as an irrigated RF-guided
      circumferential PVI and may be considered an alternative option for the index
      ablation.

PMID- 26316146
TI  - Real-time magnetic resonance-guided ablation of typical right atrial flutter
      using a combination of active catheter tracking and passive catheter
      visualization in man: initial results from a consecutive patient series.
AB  - AIMS: Recently cardiac magnetic resonance (CMR) imaging has been found feasible
      for the visualization of the underlying substrate for cardiac arrhythmias as well
      as for the visualization of cardiac catheters for diagnostic and ablation
      procedures. Real-time CMR-guided cavotricuspid isthmus ablation was performed in
      a series of six patients using a combination of active catheter tracking and
      catheter visualization using real-time MR imaging. METHODS AND RESULTS: Cardiac
      magnetic resonance utilizing a 1.5 T system was performed in patients under deep
      propofol sedation. A three-dimensional-whole-heart sequence with navigator
      technique and a fast automated segmentation algorithm was used for online
      segmentation of all cardiac chambers, which were thereafter displayed on a
      dedicated image guidance platform. In three out of six patients complete isthmus
      block could be achieved in the MR scanner, two of these patients did not need any
      additional fluoroscopy. In the first patient technical issues called for a
      completion of the procedure in a conventional laboratory, in another two patients
      the isthmus was partially blocked by magnetic resonance imaging (MRI)-guided
      ablation. The mean procedural time for the MR procedure was 109 +/- 58 min. The
      intubation of the CS was performed within a mean time of 2.75 +/- 2.21 min. Total
      fluoroscopy time for completion of the isthmus block ranged from 0 to 7.5 min.
      CONCLUSION: The combination of active catheter tracking and passive real-time
      visualization in CMR-guided electrophysiologic (EP) studies using advanced
      interventional hardware and software was safe and enabled efficient navigation,
      mapping, and ablation. These cases demonstrate significant progress in the
      development of MR-guided EP procedures.

PMID- 26316148
TI  - Efficient national surveillance for health-care-associated infections.
AB  - BACKGROUND: Detecting novel healthcare-associated infections (HCAI) as early as
      possible is an important public health priority. However, there is currently no
      evidence base to guide the design of efficient and reliable surveillance systems.
      Here we address this issue in the context of a novel pathogen spreading primarily
      between hospitals through the movement of patients. METHODS: Using a mathematical
      modelling approach we compare the current surveillance system for a HCAI that
      spreads primarily between hospitals due to patient movements as it is implemented
      in Scotland with a gold standard to determine if the current system is maximally
      efficient or whether it would be beneficial to alter the number and choice of
      hospitals in which to concentrate surveillance effort. RESULTS: We validated our
      model by demonstrating that it accurately predicts the risk of meticillin
      resistant Staphylococcus aureus bacteraemia cases in Scotland. Using the 29 (out
      of 182) sentinel hospitals that currently contribute most of the national
      surveillance effort results in an average detection time of 117 days. A reduction
      in detection time to 87 days is possible by optimal selection of 29 hospitals.
      Alternatively, the same detection time (117 days) can be achieved using just 22
      optimally selected hospitals. Increasing the number of sentinel hospitals to 38
      (teaching and general hospitals) reduces detection time by 43 days; however
      decreasing the number to seven sentinel hospitals (teaching hospitals) increases
      detection time substantially to 268 days. CONCLUSIONS: Our results show that the
      current surveillance system as it is used in Scotland is not optimal in detecting
      novel pathogens when compared to a gold standard. However, efficiency gains are
      possible by better choice of sentinel hospitals, or by increasing the number of
      hospitals involved in surveillance. Similar studies could be used elsewhere to
      inform the design and implementation of efficient national, hospital-based
      surveillance systems that achieve rapid detection of novel HCAIs for minimal
      effort.

PMID- 26316149
TI  - Effects of Iron Chelators on Pulmonary Iron Overload and Oxidative Stress in beta
      Thalassemic Mice.
AB  - AIM: To evaluate the effect of iron chelators on iron-related pulmonary pathology
      and oxidative stress in an animal model of beta-thalassemia. METHODS: Pulmonary
      iron overload was induced in heterozygous beta-globin knockout mice (mubetath
      3/+, BKO). Over a period of 2 weeks, 180 mg of iron/mouse was loaded by
      intraperitoneal injection of iron dextran, and subsequently treated daily via
      intraperitoneal with either deferoxamine (DF) or deferiprone (L1) at an equimolar
      concentration of iron binding (0.2 and 0.6 MUmol/g body weight, respectively) for
      7 days. RESULTS: Iron loading resulted in iron deposition in peribronchial
      regions, septa and also in alveolar macrophages with a grading score of 3. This
      iron burden resulted in lung epithelial injuries, fibrosis and corresponded with
      increased lipid peroxidation and decreased tissue catalase activity. Treatment
      with DF or L1 resulted in a reduction of iron-laden alveolar macrophages and
      decreased oxidative stress and tissue damage, showing the iron mobilizing ability
      of both compounds. CONCLUSION: Iron chelation therapy, with DF and L1, may
      protect against pulmonary damage by sequestering catalytic iron and improving
      oxidative status. It may be beneficial in the prevention of pulmonary
      complications in thalassemia.

PMID- 26316150
TI  - A Key Role of Autophagy in Osteoblast Differentiation on Titanium-Based Dental
      Implants.
AB  - Autophagy plays an important role in embryogenesis, for the maintenance of tissue
      homeostasis and the elimination of damaged subcellular structures. Furthermore,
      autophagy could be a mode of physiological cell death and also be implicated in
      cell differentiation. Thus, we hypothesized that autophagy may have an impact on
      the differentiation of osteoblast cells influenced by various titanium-based
      surfaces. Interactions between smooth, commercially available pure titanium (Ti
      cp), rough Ticer, acid-etched Ti cp (SS) and M1-M3 (comprised of the monoclinic
      phase of sodium-titanium oxides and rutile; M2 contains amorphous calcium
      phosphates) and human osteoblast cells were investigated. Immunofluorescent
      staining was used for detecting autophagy, cell cluster formation and collagen
      type I (Col-1) expression. Flow cytometry was employed to identify autophagy, the
      production of endogenous nitric oxide (NO) and the size and granularity of the
      cells. Rough surfaces caused osteoblast differentiation via the autophagic
      dependent PI3/Akt signalling pathway. These surfaces induced the formation of
      discrete populations of large, granular cells, i.e. mature osteoblasts. In
      addition, M1-M3 provoked the development of a third population of small, granular
      cells, responsible for cell cluster formation, which are important for the
      formation of bone noduli and mineralisation. The same surfaces induced faster
      osteoblast maturation and enhanced NO production, a hallmark of the already
      mentioned processes. Neither the mature osteoblasts nor the small cells appeared
      after the inhibition of autophagy. Inhibition of autophagy also prevented cell
      cluster formation. We demonstrate that autophagy plays an essential role in the
      osteoblast differentiation on titanium-based surfaces with rough topography.

PMID- 26316151
TI  - In vivo assessment of two endothelialization approaches on bioprosthetic valves
      for the treatment of chronic deep venous insufficiency.
AB  - Chronic deep venous insufficiency is a debilitating disease with limited
      therapeutic interventions. A bioprosthetic venous valve could not only replace a
      diseased valve, but has the potential to fully integrate into the patient with a
      minimally invasive procedure. Previous work with valves constructed from small
      intestinal submucosa (SIS) showed improvements in patients' symptoms in clinical
      studies; however, substantial thickening of the implanted valve leaflets also
      occurred. As endothelial cells are key regulators of vascular homeostasis, their
      presence on the SIS valves may reduce the observed thickening. This work tested
      an off-the-shelf approach to capture circulating endothelial cells in vivo using
      biotinylated antikinase insert domain receptor antibodies in a suspended leaflet
      ovine model. The antibodies on SIS were oriented to promote cell capture and
      showed positive binding to endothelial cells in vitro; however, no differences
      were observed in leaflet thickness in vivo between antibody-modified and
      unmodified SIS. In an alternative approach, valves were pre-seeded with
      autologous endothelial cells and tested in vivo. Nearly all the implanted pre
      seeded valves were patent and functioning; however, no statistical difference was
      observed in valve thickness with cell pre-seeding. Additional cell capture
      schemes or surface modifications should be examined to find an optimal method for
      encouraging SIS valve endothelialization to improve long-term valve function in
      vivo. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater,
      104B: 1610-1621, 2016.

PMID- 26316152
TI  - Convergent synthesis of double point modified analogs of 1alpha,25
      dihydroxyvitamin D2 for biological evaluation.
AB  - There is a long lasting controversy over the biological activity of vitamin D2 as
      compared to vitamin D3 in terms of maintaining of calcium homeostasis and raising
      the level of circulating 25-OH-D. To shed more light on this relationship we
      synthesized 1alpha,25-dihydroxyvitamin D2, by a novel convergent strategy, to
      compare this compound directly with the activity of 1alpha,25-dihydroxyvitamin
      D3. The same synthetic strategy also provided a series of (5E,7E) geometric
      isomers of the natural 1alpha,25-dihydroxyvitamin D2 as well as a series of
      double point modified analogs of its (24R)-epimer, including C-22 hydroxy
      derivatives. The structure of the new analogs was determined by 1H and 13C NMR as
      well as by mass spectrometry. The influence of (5E,7E) modification, alone or in
      combination with additional modifications in the side chain, on the activity
      profile and metabolic deactivation of analogs of 1alpha,25-dihydroxyvitamin D2
      still remains unknown. (5E,7E) modification in the structure of new analogs of
      1alpha,25-dihydroxyvitamin D2 is expected to give analogs with no influence on
      calcium level, as was previously obtained for the analogs of 1alpha,25
      dihydroxyvitamin D3. Investigation of the affinities for the vitamin D receptor
      and cell differentiation, transcriptional and calcium activities of the most
      active form of vitamin D2 and of (5E,7E) analogs, compared to 1alpha,25
      dihydroxyvitamin D3, is underway in the collaborating laboratories.

PMID- 26316153
TI  - Identification of TRIM22 as a progesterone-responsive gene in Ishikawa
      endometrial cancer cells.
AB  - Progesterone plays important roles in implantation and maintains pregnancy. It
      antagonizes estrogen-mediated cell proliferation and promotes differentiation in
      the uterus. The action of progesterone is mediated by specific receptors, namely,
      the progesterone receptors (PRs). We generated two Ishikawa cell clones stably
      expressing PR isoform A (PR-A) and identified progesterone-responsive genes using
      cDNA microarray analysis. Fifteen genes were identified as progesterone
      responsive gene candidates by microarray analysis and their progesterone
      responsiveness was shown by quantitative reverse transcriptase polymerase chain
      reaction (qRT-PCR) analysis. Out of these 15 genes, we focused on TRIM22. A
      database search revealed a progesterone response element (PRE) located from the 
      25 to -11 bp region upstream of TRIM22 exon 1. This PRE had a 1-bp mismatch in
      the consensus PRE sequence. A chromatin immunoprecipitation assay revealed that
      the interaction of PR with the TRIM22 PRE region increased in a hormone-dependent
      manner. The progesterone-dependent enhancer activity of TRIM22 PRE was
      demonstrated using a luciferase assay. Based on these results, we propose that
      TRIM22 is a direct target gene of PR and that it can mediate progesterone actions
      in uterine cells.

PMID- 26316154
TI  - Randomized clinical trial of transcutaneous electrical posterior tibial nerve
      stimulation versus lateral internal sphincterotomy for treatment of chronic anal
      fissure.
AB  - OBJECTIVES: The objective of this study was to evaluate the efficacy of
      transcutaneous electrical posterior tibial nerve stimulation in treatment of
      patients with chronic anal fissure and to compare it with the conventional
      lateral internal sphincterotomy. PATIENTS AND METHODS: Consecutive patients with
      chronic anal fissure were randomly allocated into two treatment groups:
      transcutaneous electrical posterior tibial nerve stimulation group and lateral
      internal sphincterotomy group. The primary outcome measures were number of
      patients with clinical improvement and healed fissure. Secondary outcome measures
      were complications, VAS pain scores, Wexner's constipation and Peascatori anal
      incontinence scores, anorectal manometry, and quality of life index. RESULTS:
      Seventy-three patients were randomized into two groups of 36 patients who were
      subjected to transcutaneous electrical nerve stimulation and 37 patients who
      underwent lateral internal sphincterotomy. All (100%) patients in lateral
      internal sphincterotomy group had clinical improvement at one month following the
      procedure in contrast to 27 (75%) patients in transcutaneous electrical nerve
      stimulation group. Recurrence of anal fissure after one year was reported in one
      (2.7%) and 11 (40.7%) patients in lateral internal sphincterotomy and
      transcutaneous electrical nerve stimulation groups respectively. Resting anal
      pressure and functional anal canal length were significantly reduced after
      lateral internal sphincterotomy. CONCLUSION: Transcutaneous electrical posterior
      tibial nerve stimulation for treatment of chronic anal fissure is a novel, non
      invasive procedure and has no complications. However, given the higher rate of
      clinical improvement and fissure healing and the lower rate of fissure
      recurrence, lateral internal sphincterotomy remains the gold standard for
      treating chronic anal fissure.

PMID- 26316155
TI  - Oncological strategies for middle and low rectal cancer with synchronous liver
      metastases.
AB  - PURPOSES: In rectal cancer, the incidence of synchronous liver metastases (SLM)
      ranges from 14% to 30%. The treatment of SLM combines neo-adjuvant chemo- and/or
      radiotherapy with of one three surgical resection strategies (rectal resection
      first, liver resection first or simultaneous resection). The present study
      evaluated the success rate for each resection strategy. METHODS: From January
      2005 to December 2013, we retrospectively included all patients with distal
      (middle and low) rectal cancer (MLRC) and SLM and who had been operated on with
      curative intent. The primary study endpoint was the proportion of complete
      resections at both tumour sites. The secondary endpoints were postoperative
      morbidity, the long-term outcome and risk factors for incomplete resection.
      RESULTS: 52 patients were included. There were no significant intergroup
      differences in the incidence of complete resection (respectively 74%, 66% and 50%
      in the rectum-first (n = 20), simultaneous (n = 10) and liver-first groups (n =
      5); p = 0.3), the overall complication rate or mortality rate after rectal
      resection (p = 0.5) or liver resection (p = 0.8), overall survival (60, 47 and 38
      months, respectively; p = 0.4) or disease-free survival (31, 32 and 7.8 months,
      respectively; p = 0.1). Emergency surgery was the only risk factor for treatment
      failure (p = 0.01). CONCLUSION: There were no differences in short and long-term
      outcomes between the three strategies. No one oncological strategy should be
      favoured for all cases of MLRC with SLM. The strategy should be choosen, based on
      the oncological emergency (rectum-first or liver-first), predictive factors for
      morbidity in rectal surgery and MDT discussion.

PMID- 26316156
TI  - Long-term results of the David Procedure in patients with acute type A aortic
      dissection.
AB  - INTRODUCTION: The David Procedure may provide an attractive alternative to aortic
      root replacement in patients with aortic valve insufficiency (AI) even in the
      emergency setting of an acute type A aortic dissection (AAD). METHODS: From 1996
      to 2011 the David Procedure was performed in 23 patients with AAD in our
      department. Patients' mean age was 49 +/- 15 years and 70% (n = 16) were male.
      Concomitant hemiarch replacement was performed in 19 patients while the remaining
      4 patients underwent full arch replacement. Additional leaflet prolapse was
      corrected by plication in 5 cases. A modification of the classic David technique
      was performed by creating a pseudosinus in 6 patients (26%) and a neosinus in 9
      patients (39%). Mean follow up was 7.7 +/- 3 years. RESULTS: Thirty-day mortality
      was zero. There were 4 late deaths (17%). One patient suffered a perioperative
      neurologic event (4%). One further patient suffered a late stroke during follow
      up (0.6%/pt-yr). Three patients (1.7%/pt-yr) required aortic valve reoperation
      during follow up: in 2 cases leaflet perforation was observed, and one patient
      had to undergo valve replacement because of endocarditis with severe AI. There
      were two cases of bleeding events (1.1%/pt-yr) at follow up. The linearized rate
      for recurrent AI >= 2 degrees  was 1.1%/pt-yr. DISCUSSION: The David Procedure
      certainly provides a challenging option to treat selected young patients with AI
      in the presence of AAD. However, current data suggest that it is safe and
      feasible. CONCLUSIONS: Long-term valve-related events of the David Procedure
      applied in emergency cases are rare and aortic valve function remains stable for
      many years.

PMID- 26316157
TI  - Preventing transfer of infectious agents.
AB  - Xenotransplantation using pig cells, tissues and organs may be associated with
      the transfer of porcine infectious agents, which may infect the human recipient
      and in the worst case induce a disease (zoonosis). To prevent this, a broad
      screening program of the donor animals for putative zoonotic microorganisms,
      including bacteria, viruses, fungi and others, using sensitive and specific
      detection methods has to be performed. As long as it is still unknown, which
      microorganism represents a real risk for the recipient, experience from
      allotransplantation should be brought in. Due to the fact that pigs can be
      screened long before the date of transplantation, xenotransplantation will become
      eventually safer compared with allotransplantation. Screening and selection of
      animals free of potential zoonotic microorganisms, Caesarean section, vaccination
      and/or treatment with chemotherapeutics are the strategies of choice to obtain
      donor animals not transmitting microorganisms. In the case of porcine endogenous
      retroviruses (PERVs) which are integrated in the genome of all pigs and which
      cannot be eliminated this way, selection of animals with low virus expression and
      generation of genetically modified pigs suppressing PERV expressions may be
      performed. 

PMID- 26316158
TI  - Synthesis of Adjacent Quaternary Stereocenters by Catalytic Asymmetric
      Allylboration.
AB  - Allylboration of ketones with gamma-disubstituted allylboronic acids is performed
      in the presence of chiral BINOL derivatives. The reaction is suitable for single
      step creation of adjacent quaternary stereocenters with high selectivity. We show
      that, with an appropriate choice of the chiral catalyst and the stereoisomeric
      prenyl substrate, full control of the stereo- and enantioselectivity is possible
      in the reaction. 

PMID- 26316160
TI  - Development of glutathione-conjugated asiatic acid-loaded bovine serum albumin
      nanoparticles for brain-targeted drug delivery.
AB  - OBJECTIVE: Asiatic acid, a well-known plant-based neuroprotective pentacyclic
      triterpenoid, has major limitation for its bioavailability in the brain. The
      objective of this study is to develop novel bovine serum albumin (BSA)
      nanoparticles coupled with glutathione (natural tripeptide) to enhance drug
      delivery to brain. METHODS: Asiatic acid-loaded BSA nanoparticles were prepared
      by using modified desolvation technique. Conjugation of glutathione with asiatic
      acid-loaded BSA nanoparticle was done by carbodiimide reaction using 1-ethyl-3-(3
      dimethylaminopropyl) carbodiimide (EDAC). In-vivo biodistribution study of
      asiatic acid solution, and conjugated and unconjugated asiatic acid-loaded BSA
      nanoparticles, at the dose equivalent to 75 mg/kg was evaluated, through
      intravenous administration to Wistar rats. Asiatic acid has very weak chromophore
      so high-pressure liquid chromatography-based novel pre-derivatization method was
      developed using p-toluidine as a coupling agent to improve sensitivity. KEY
      FINDINGS: The results showed 10-fold more bioavailability of asiatic acid in the
      brain after 5 h with glutathione-conjugated asiatic acid-loaded BSA nanoparticles
      as compared with asiatic acid solution with 627.21% drug targeting efficiency to
      the brain. CONCLUSION: The present investigation demonstrated enhanced delivery
      of asiatic acid using glutathione and hence served as a potential ligand to
      improve brain targeting efficiency.

PMID- 26316159
TI  - Next-generation sequencing: hype and hope for development of personalized
      radiation therapy?
AB  - The introduction of next-generation sequencing (NGS) in the field of cancer
      research has boosted worldwide efforts of genome-wide personalized oncology
      aiming at identifying predictive biomarkers and novel actionable targets. Despite
      considerable progress in understanding the molecular biology of distinct cancer
      entities by the use of this revolutionary technology and despite contemporaneous
      innovations in drug development, translation of NGS findings into improved
      concepts for cancer treatment remains a challenge. The aim of this article is to
      describe shortly the NGS platforms for DNA sequencing and in more detail key
      achievements and unresolved hurdles. A special focus will be given on potential
      clinical applications of this innovative technique in the field of radiation
      oncology. 

PMID- 26316161
TI  - Biochemical and Pharmacokinetic Properties of PEGylated Cystathionine gamma-Lyase
      from Aspergillus carneus KF723837.
AB  - Cystathionine gamma-lyase (CGL) was purified to its electrophoretic homogeneity
      from Aspergillus carneus by various chromatographic approaches. The purified
      enzyme has four identical subunits of 52 kDa based on SDS and native PAGE
      analyses. To improve its structural stability, purified CGL was modified by
      covalent binding to polyethylene glycol moieties. The specific activity of free
      CGL and PEG-CGL was 59.71 and 48.71 U/mg, respectively, with a PEGylation yield
      of 81.5 and 70.7% modification of surface epsilon-amino groups. Free- and
      modified CGL have the same pattern of pH stability (8.0-9.0). At 50  degrees C,
      the thermal stability [half-life time (T1/2)] of PEG-CGL was increased by 40% in
      comparison to free-CGL. The activity of CGL was completely inhibited by
      hydroxylamine and Hg(+2), with no effect by EDTA. Free-CGL (0.04 mM(-1)s(-1)) and
      PEG-CGL (0.03 mM(-1)s(-1)) have a similar catalytic efficiency to L-cystathionine
      as a substrate. The inhibition constant values of propargylglycine were 0.31 and
      0.52 uM for the free- and PEG-CGL, respectively. By in vitro proteolysis, PEG-CGL
      retains >50% of its initial activity compared to <10% of the free-CGL for acid
      protease for 30 min. From in vivo pharmacokinetics in New Zealand white rabbits,
      the T1/2 was 19.1 and 28.9 h for the Holo free-CGL and PEG-CGL, respectively,
      ensuring the role of PEGylation on shielding the CGL surface from proteolytic
      attack, reducing its antigenicity, and stabilizing its internal Schiff base. By
      external infusion of pyridoxal 5'-phosphate (10 uM), the T1/2 of free- and PEG
      CGL was prolonged to 24 and 33 h, respectively, so dissociation of pyridoxal 5'
      phosphate was one of the main causes of loss of enzyme activity. The biochemical
      and hematological responses of rabbits to free- and PEG-CGL were assessed, with
      relative similarity to the negative control, confirming the nil toxicity of
      enzymes. The titer of IgG was duplicated in response to free- versus PEG-CGL
      after 45 days. To the best of our knowledge, this is the first report concerned
      with purification and PEGylation of CGL from fungi, with higher affinity for L
      cystathionine. With further molecular studies, CGL will be a promising enzyme
      against various cardiovascular diseases and antioxidant deficiency, as well as
      for generation of a neurotransmitter (H2S).

PMID- 26316162
TI  - (Bi)Weekly folic acid supplementation might be inferior to a daily folic acid
      dosing schedule in the prevention of methotrexate-related toxicity in patients
      with rheumatoid arthritis.

PMID- 26316163
TI  - Genomic characterization of a US porcine kobuvirus strain.
AB  - Porcine kobuvirus has been detected from pig fecal samples in the USA, but there
      is still no information on the full-length genomes. In this study, we
      characterized the first complete genomic sequence of a US porcine kobuvirus
      strain OH/RV50/2011. The viral genome is 8123 nucleotides (nt) long, including a
      576-nt 5'-untranslated region (UTR), a 7380-nt polyprotein encoding sequence, and
      a 167-nt 3'-UTR. A complete genome sequence alignment suggested that two types of
      porcine kobuviruses were found based on whether a 30-aa deletion existed in the
      2B encoding region. Furthermore, several conserved motifs that can be used for
      the design of universal kobuvirus or porcine kobuvirus-specific primers were
      verified in non-structural protein genes. Phylogenetic analysis based on the
      complete genome sequence showed that RV50 was grouped with other porcine
      kobuviruses and more closely related to Chinese strains. Secondary structure
      analysis of the 5'-UTR showed that RV50 has three stem-loop domains in the first
      108 nt and has a potential hepacivirus-/pestivirus-like type IV group-B-like
      internal ribosomal entry site, like the porcine kobuvirus prototype strain S-1.
      Codon usage analysis showed that the most preferred usage tends to be C or U at
      the end of a codon in a porcine kobuvirus genome. These results will be useful in
      understanding the evolution of porcine kobuviruses . 

PMID- 26316164
TI  - Hydrogen peroxide causes Vibrio vulnificus bacteriolysis accelerated by sulfonyl
      fluoride compounds.
AB  - Induction of bacteriolysis of Vibrio vulnificus cells by 10 mM hydrogen peroxide
      (H(2)O(2)) was analyzed. All Vibrio species examined, except for Vibrio hollisae,
      were lysed by 10 mM H(2)O(2). Bacteriophage induction was not the cause of
      H(2)O(2)-induced bacteriolysis. Autolysis is also known to cause bacteriolysis.
      VvpS protein is a serine protease of V. vulnificus essential for autolysis. vvpS
      mutant underwent H(2)O(2)-induced bacteriolysis in the same manner as the wild
      type. Protease inhibitors including serine protease inhibitors did not inhibit
      H(2)O(2)-induced bacteriolysis, which means that bacteriolysis is not due to
      autolysis. Unexpectedly, H(2)O(2)-induced bacteriolysis was accelerated by adding
      4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) and
      phenylmethylsulfonyl fluoride which are serine protease inhibitors. The hydroxyl
      radical was generated by H(2)O(2)-AEBSF interaction. It was considered that
      H(2)O(2)-induced bacteriolysis was caused by the hydroxyl radical which was
      generated by Fenton reaction, and possibly mediated by AEBSF. Deferoxamine, an
      agent chelating ferric ion and Fenton reaction inhibitor, suppressed both
      H(2)O(2)-induced bacteriolysis and its acceleration by AEBSF. This suggests that
      both phenomena were Fenton reaction dependent, and hydroxyl radical generated by
      Fenton reaction caused bacteriolysis of V. vulnificus though the reason for high
      susceptibility of Vibrio species to hydroxyl radical is not known.

PMID- 26316165
TI  - Photolithographic Encoding of Metal Complexes.
AB  - A platform technology for the creation of spatially resolved surfaces encoded
      with a monolayer consisting of different metal complexes was developed. The
      concept entails the light-triggered activation of a self- assembled monolayer
      (SAM) of UV-labile anchors, that is, phenacylsulfides, and the subsequent
      cycloaddition of selected diene-functionalized metal complexes at defined areas
      on the surface. The synthesis and characterization of the metal complexes for the
      UV-light assisted anchoring on the surface and a detailed study of a short-chain
      oligomer model system in solution confirm the high efficiency of the
      photoreaction. The hybrid materials obtained by this concept can potentially be
      utilized for the design of highly valuable catalytic or (opto-)electronic
      devices. 

PMID- 26316166
TI  - Regulatory T cells in cancer; can they be controlled?

PMID- 26316167
TI  - Inhibition of CD147 expression by RNA interference reduces proliferation,
      invasion and increases chemosensitivity in cancer stem cell-like HT-29 cells.
AB  - The association between CD147 and cancer stem cells (CSCs) provides a new angle
      for cancer treatments. The aim of this study was to investigate the biological
      roles of CD147 in colorectal CSCs. The Oct4-green fluorescent protein (GFP)
      vector was used to isolate CSCs and pYr-mir30-shRNA was used to generate short
      hairpin RNA (shRNA) specifically for CD147. After RNA interference (RNAi), CD147
      was evaluated by reverse transcription-quantitative PCR and western blot
      analysis, and its biological functions were assessed by MTT and invasion assays.
      The results showed that the differentiation of isolated CSC-like HT-29 cells was
      blocked and these cells were highly positive for CD44 and CD147. RNAi-mediated
      CD147 silencing reduced the expression of CD147 at both mRNA and protein levels.
      Moreover, the activities of proliferation and invasion were decreased obviously
      in CSCs. Knockdown of CD147 increased the chemosensitivity of CSC-like cells to
      gemcitabine, cisplatin, docetaxel at 0.1, 1 and 10 uM respectively, however,
      there was no significant difference among the three groups to paclitaxel at 10
      uM. In conclusion, these results suggest that CD147 plays an important role in
      colorectal CSCs and might be regarded as a novel CSC-specific targeted strategy
      against colorectal cancer.

PMID- 26316168
TI  - Balance and coordination training, but not endurance training, enhances
      synaptophysin and neurotrophin-3 immunoreactivity in the lumbar spinal cord after
      sciatic nerve crush.
AB  - INTRODUCTION: Numerous rehabilitation treatments have been shown to be useful for
      peripheral and central restoration after (PNI). METHODS: After sciatic nerve
      crush, we investigated 4 weeks of endurance training (ET) and balance and
      coordination training (BCT) with sciatic function index, hind-paw stride length,
      and spinal cord dorsal horn synaptophysin and neurotrophin-3 immunoreactivity.
      RESULTS: Our results demonstrated no significant differences between the non
      trained (NT), ET, and BCT groups in sciatic functional index, and in stride
      length analysis, but the ET showed higher values compared with the NT group.
      Synaptophysin immunoreactivity was higher in the BCT group compared with the NT
      group, and neurotrophin-3 immunoreactivity in the BCT group was greater compared
      with the other groups. CONCLUSION: BCT can positively affect spinal cord
      plasticity after a (PNI), and these modifications are important in the
      rehabilitation process.

PMID- 26316169
TI  - Escalation and De-escalation of Therapy in COPD: Myths, Realities and
      Perspectives.
AB  - Chronic obstructive pulmonary disease (COPD) guidelines and strategies suggest
      escalating treatment, mainly depending on the severity of airflow obstruction.
      However, some de-escalation of therapy in COPD would be appropriate, although we
      still do not know when we should switch, step-up or step-down treatments in our
      patients. Unfortunately, trials comparing different strategies of step-up and
      step-down treatment (e.g. treatment initiation with one single agent and then
      further step-up if symptoms are not controlled versus initial use of double or
      triple therapy, possibly with lower doses of the individual components, or the
      role of N-acetylcysteine in combination therapy for a step-down approach) are
      still lacking. In general, there is a large and often inappropriate use of the
      inhaled corticosteroid (ICS)/long-acting beta2-agonist (LABA) combination.
      However, the withdrawal of the ICS in COPD patients at low risk of exacerbation
      can be safe, provided that patients are under regular treatment with long-acting
      bronchodilators. Maximising the treatment in patients with a degree of clinical
      instability by including an ICS in the therapeutic regimen is useful to control
      the disease, but may not be needed during periods of clinical stability. In
      patients with severe but stable COPD, the withdrawal of the ICS from triple
      therapy [LABA + long-acting muscarinic antagonist (LAMA) + ICS] is possible, but
      not when the patient has been hospitalised for an acute exacerbation of COPD. We
      must still establish how long we should wait before withdrawing the ICS. It is
      still unclear whether the same is true when only the LABA or the LAMA is
      withdrawn while continuing treatment with the other bronchodilator and the ICS.
      In any case, we strongly believe that it is always better to avoid a therapeutic
      step-up progression when it is not needed rather than being forced subsequently
      into a step-down approach in which the outcome is always unpredictable.

PMID- 26316171
TI  - Public Health Nurses' Experiences in Caring for the Fukushima Community in the
      Wake of the 2011 Fukushima Nuclear Accident.
AB  - OBJECTIVE: This study described public health nurses' (PHNs) experiences in
      caring for people in their communities during the recovery stage of the Fukushima
      nuclear accident. DESIGN AND SAMPLE: Forty-four PHNs responded to an open-ended
      questionnaire administered before a radiation protection workshop and
      participated in interviews after the workshop. Data were qualitatively analyzed.
      RESULTS: Two major themes were identified: (1) profound powerlessness and (2)
      compelling sense of mission. The participants cared for people driven by their
      compelling sense of mission, despite not having the correct information or
      sufficient knowledge. They spoke of being heart-broken and barely able to face
      the reality of the impact of the accident. CONCLUSIONS: PHNs supported people
      because of a compelling sense of mission yet it was a great burden. Education
      about radiation and radiation protection for nursing students and PHNs, two-way
      communication between PHNs and radiation specialists, long-term support by
      specialists, and the opportunity for PHNs to share their feelings and experiences
      is necessary.

PMID- 26316172
TI  - Nonlocal Total-Variation-Based Speckle Filtering for Ultrasound Images.
AB  - Ultrasound is one of the most important medical imaging modalities for its real
      time and portable imaging advantages. However, the contrast resolution and
      important details are degraded by the speckle in ultrasound images. Many speckle
      filtering methods have been developed, but they are suffered from several
      limitations, difficult to reach a balance between speckle reduction and edge
      preservation. In this paper, an adaptation of the nonlocal total variation (NLTV)
      filter is proposed for speckle reduction in ultrasound images. The speckle is
      modeled via a signal-dependent noise distribution for the log-compressed
      ultrasound images. Instead of the Euclidian distance, the statistical Pearson
      distance is introduced in this study for the similarity calculation between image
      patches via the Bayesian framework. And the Split-Bregman fast algorithm is used
      to solve the adapted NLTV despeckling functional. Experimental results on
      synthetic and clinical ultrasound images and comparisons with some classical and
      recent algorithms are used to demonstrate its improvements in both speckle noise
      reduction and tissue boundary preservation for ultrasound images.

PMID- 26316170
TI  - Identification of a New Susceptibility Locus for Systemic Lupus Erythematosus on
      Chromosome 12 in Individuals of European Ancestry.
AB  - OBJECTIVE: Genome-wide association studies (GWAS) in individuals of European
      ancestry identified a number of systemic lupus erythematosus (SLE) susceptibility
      loci using earlier versions of high-density genotyping platforms. Followup
      studies on suggestive GWAS regions using larger samples and more markers
      identified additional SLE loci in subjects of European descent. This multistage
      study was undertaken to identify novel SLE loci. METHODS: In stage 1, we
      conducted a new GWAS of SLE in a North American case-control sample of subjects
      of European ancestry (n = 1,166) genotyped on Affymetrix Genome-Wide Human SNP
      Array 6.0. In stage 2, we further investigated top new suggestive GWAS hits by in
      silico evaluation and meta-analysis using an additional data set of subjects of
      European descent (>2,500 individuals), followed by replication of top meta
      analysis findings in another data set of subjects of European descent (>10,000
      individuals) in stage 3. RESULTS: As expected, our GWAS revealed the most
      significant associations at the major histocompatibility complex locus (6p21),
      which easily surpassed the genome-wide significance threshold (P < 5 * 10(-8)).
      Several other SLE signals/loci previously implicated in Caucasians and/or Asians
      were also confirmed in the stage 1 discovery sample, and the strongest signals
      were observed at 2q32/STAT4 (P = 3.6 * 10(-7)) and at 8p23/BLK (P = 8.1 * 10(
      6)). Stage 2 meta-analyses identified a new genome-wide significant SLE locus at
      12q12 (meta P = 3.1 * 10(-8)), which was replicated in stage 3. CONCLUSION: Our
      multistage study identified and replicated a new SLE locus that warrants further
      followup in additional studies. Publicly available databases suggest that this
      newly identified SLE signal falls within a functionally relevant genomic region
      and near biologically important genes.

PMID- 26316173
TI  - Prior knowledge driven Granger causality analysis on gene regulatory network
      discovery.
AB  - BACKGROUND: Our study focuses on discovering gene regulatory networks from time
      series gene expression data using the Granger causality (GC) model. However, the
      number of available time points (T) usually is much smaller than the number of
      target genes (n) in biological datasets. The widely applied pairwise GC model
      (PGC) and other regularization strategies can lead to a significant number of
      false identifications when n>>T. RESULTS: In this study, we proposed a new
      method, viz., CGC-2SPR (CGC using two-step prior Ridge regularization) to resolve
      the problem by incorporating prior biological knowledge about a target gene data
      set. In our simulation experiments, the propose new methodology CGC-2SPR showed
      significant performance improvement in terms of accuracy over other widely used
      GC modeling (PGC, Ridge and Lasso) and MI-based (MRNET and ARACNE) methods. In
      addition, we applied CGC-2SPR to a real biological dataset, i.e., the yeast
      metabolic cycle, and discovered more true positive edges with CGC-2SPR than with
      the other existing methods. CONCLUSIONS: In our research, we noticed a " 1+1>2"
      effect when we combined prior knowledge and gene expression data to discover
      regulatory networks. Based on causality networks, we made a functional prediction
      that the Abm1 gene (its functions previously were unknown) might be related to
      the yeast's responses to different levels of glucose. Our research improves
      causality modeling by combining heterogeneous knowledge, which is well aligned
      with the future direction in system biology. Furthermore, we proposed a method of
      Monte Carlo significance estimation (MCSE) to calculate the edge significances
      which provide statistical meanings to the discovered causality networks. All of
      our data and source codes will be available under the link
      https://bitbucket.org/dtyu/granger-causality/wiki/Home.

PMID- 26316174
TI  - Genetic polymorphisms associated with the inflammatory response in bacterial
      meningitis.
AB  - BACKGROUND: Bacterial meningitis (BM) is an infectious disease that results in
      high mortality and morbidity. Despite efficacious antibiotic therapy,
      neurological sequelae are often observed in patients after disease. Currently,
      the main challenge in BM treatment is to develop adjuvant therapies that reduce
      the occurrence of sequelae. In recent papers published by our group, we described
      the associations between the single nucleotide polymorphisms (SNPs) AADAT +401C >
      T, APEX1 Asn148Glu, OGG1 Ser326Cys and PARP1 Val762Ala and BM. In this study, we
      analyzed the associations between the SNPs TNF -308G > A, TNF -857C > T, IL-8 
      251A > T and BM and investigated gene-gene interactions, including the SNPs that
      we published previously. METHODS: The study was conducted with 54 BM patients and
      110 healthy volunteers (as the control group). The genotypes were investigated
      via primer-introduced restriction analysis-polymerase chain reaction (PIRA-PCR)
      or polymerase chain reaction-based restriction fragment length polymorphism (PCR
      RFLP) analysis. Allelic and genotypic frequencies were also associated with
      cytokine and chemokine levels, as measured with the x-MAP method, and cell
      counts. We analyzed gene-gene interactions among SNPs using the generalized
      multifactor dimensionality reduction (GMDR) method. RESULTS: We did not find
      significant association between the SNPs TNF -857C > T and IL-8 -251A > T and the
      disease. However, a higher frequency of the variant allele TNF -308A was observed
      in the control group, associated with changes in cytokine levels compared to
      individuals with wild type genotypes, suggesting a possible protective role. In
      addition, combined inter-gene interaction analysis indicated a significant
      association between certain genotypes and BM, mainly involving the alleles APEX1
      148Glu, IL8 -251 T and AADAT +401 T. These genotypic combinations were shown to
      affect cyto/chemokine levels and cell counts in CSF samples from BM patients.
      CONCLUSIONS: In conclusion, this study revealed a significant association between
      genetic variability and altered inflammatory responses, involving important
      pathways that are activated during BM. This knowledge may be useful for a better
      understanding of BM pathogenesis and the development of new therapeutic
      approaches.

PMID- 26316177
TI  - Italian AKI Guidelines: The Best of the KDIGO and ADQI Results.

PMID- 26316176
TI  - Implementation of recommended non-pharmacotherapy in rheumatology practice: need
      for improvement.

PMID- 26316175
TI  - International veterinary epilepsy task force consensus proposal: diagnostic
      approach to epilepsy in dogs.
AB  - This article outlines the consensus proposal on diagnosis of epilepsy in dogs by
      the International Veterinary Epilepsy Task Force. The aim of this consensus
      proposal is to improve consistency in the diagnosis of epilepsy in the clinical
      and research settings. The diagnostic approach to the patient presenting with a
      history of suspected epileptic seizures incorporates two fundamental steps: to
      establish if the events the animal is demonstrating truly represent epileptic
      seizures and if so, to identify their underlying cause. Differentiation of
      epileptic seizures from other non-epileptic episodic paroxysmal events can be
      challenging. Criteria that can be used to make this differentiation are presented
      in detail and discussed. Criteria for the diagnosis of idiopathic epilepsy (IE)
      are described in a three-tier system. Tier I confidence level for the diagnosis
      of IE is based on a history of two or more unprovoked epileptic seizures
      occurring at least 24 h apart, age at epileptic seizure onset of between six
      months and six years, unremarkable inter-ictal physical and neurological
      examination, and no significant abnormalities on minimum data base blood tests
      and urinalysis. Tier II confidence level for the diagnosis of IE is based on the
      factors listed in tier I and unremarkable fasting and post-prandial bile acids,
      magnetic resonance imaging (MRI) of the brain (based on an epilepsy-specific
      brain MRI protocol) and cerebrospinal fluid (CSF) analysis. Tier III confidence
      level for the diagnosis of IE is based on the factors listed in tier I and II and
      identification of electroencephalographic abnormalities characteristic for
      seizure disorders. The authors recommend performing MRI of the brain and routine
      CSF analysis, after exclusion of reactive seizures, in dogs with age at epileptic
      seizure onset <6 months or >6 years, inter-ictal neurological abnormalities
      consistent with intracranial neurolocalisation, status epilepticus or cluster
      seizure at epileptic seizure onset, or a previous presumptive diagnosis of IE and
      drug-resistance with a single antiepileptic drug titrated to the highest
      tolerable dose.This consensus article represents the basis for a more
      standardised diagnostic approach to the seizure patient. These recommendations
      will evolve over time with advances in neuroimaging, electroencephalography, and
      molecular genetics of canine epilepsy.

PMID- 26316178
TI  - Hematopoietic cyclooxygenase-2 deficiency increases adipose tissue inflammation
      and adiposity in obesity.
AB  - OBJECTIVE: Adipose tissue (AT) macrophages mediate AT inflammation in obesity,
      and cyclooxygenase-2 (COX-2) is a major inflammatory gene. It was hypothesized
      that deletion of hematopoietic COX-2 will inhibit AT inflammation in obesity.
      METHODS: Lethally irradiated wild-type (WT) mice were injected with bone marrow
      (BM) cells collected from WT or COX-2 knock-out (COX-2-/-) donor mice and fed a
      high-fat diet for 16 weeks. RESULTS: The mice that received BM cells from COX-2-/
      mice (BM-COX-2-/-) gained increased body weight, fat mass, and visceral AT (VAT)
      mass. These mice exhibited reduced inflammatory markers in the VAT stromal
      vascular cells (SVC). However, the inflammatory markers were increased in
      adipocyte fraction and/or whole VAT. The activation of ERK1/2 MAPK, a pro
      inflammatory signaling pathway, was increased in BM-COX-2-/- mice. The molecular
      markers of adipogenesis were increased in the VAT or adipocyte fraction. Wnt
      signaling markers which inhibit adipogenesis, including Wnt3A and DVL3, were
      reduced, and Wnt5a/b which promotes inflammation was increased in the VAT and/or
      adipocytes. Finally, an increase in hepatic triglyceride levels in BM-COX-2-/-
      mice was noted. CONCLUSIONS: The data suggest that COX-2 deletion in
      hematopoietic cells reduces SVC inflammation but increases VAT inflammation and
      promotes adiposity likely via altered Wnt signaling.

PMID- 26316180
TI  - Delivery of a very low birth weight infant and increased maternal risk of cancer
      and death: a population study with 16 years of follow-up.
AB  - BACKGROUND: Pregnancy complications represent sentinel events for women's future
      health. We investigated whether delivery of a very low birth weight (VLBW) infant
      is associated with increased maternal risk for future incidence of maternal
      cancer and death. METHODS: This is a population-based cohort study of linked
      Israeli Ministry of Health datasets between 1995 and 2011. Women delivering a
      live singleton <1,500 g infant (VLBW group) were compared with women delivering a
      live singleton, 3,000-3,500 g (control). The first pregnancy eligible for entry
      into the study, the "index pregnancy," reflected exposure status for each
      participant. Primary outcomes were maternal cancer and death. Cancer diagnoses
      were further classified by primary site. Cox regression models adjusted for
      follow-up period and maternal characteristics at index pregnancy: Age at
      delivery, ethnicity, years of education, marital status, and previous cancer
      afforded calculation of hazard ratios (HR) and 95% confidence intervals (CI).
      FINDINGS: During the study period, 982,091 mothers with 2,243,736 live births
      were identified; of these, 13,773 births were VLBW eligible for inclusion in the
      study and 448,743 births were controls. Groups differed significantly by average
      follow-up and all maternal characteristics evaluated. Overall rate of cancers and
      death was significantly increased for VLBW women compared to controls: 18.4
      versus 15.7% and 7.3 versus 3.2%, both p < 0.0001. The Cox model adjusted for
      maternal characteristics showed significantly increased risk of cancer (all
      sites) in the VLBW women: HR 1.18 (95% CI 1.02-1.37) and for death: HR 2.13 (95%
      CI 1.68-2.71), and an increased combined risk of both outcomes: HR 1.4 (95% CI
      1.23-1.59). INTERPRETATION: The delivery of a VLBW newborn is an independent
      lifetime risk factor for subsequent maternal cancers and death. These women may
      benefit from targeted cancer screening and counseling.

PMID- 26316179
TI  - On-bead antibody-small molecule conjugation using high-capacity magnetic beads.
AB  - Antibodies labeled with small molecules such as fluorophore, biotin or drugs play
      an important role in various areas of biological research, drug discovery and
      diagnostics. However, the majority of current methods for labeling antibodies is
      solution-based and has several limitations including the need for purified
      antibodies at high concentrations and multiple buffer exchange steps. In this
      study, a method (on-bead conjugation) is described that addresses these
      limitations by combining antibody purification and conjugation in a single
      workflow. This method uses high capacity-magnetic Protein A or Protein G beads to
      capture antibodies directly from cell media followed by conjugation with small
      molecules and elution of conjugated antibodies from the beads. High-capacity
      magnetic antibody capture beads are key to this method and were developed by
      combining porous and hydrophilic cellulose beads with oriented immobilization of
      Protein A and Protein G using HaloTag technology. With a variety of fluorophores
      it is shown that the on-bead conjugation method is compatible with both thiol-
      and amine-based chemistry. This method enables simple and rapid processing of
      multiple samples in parallel with high-efficiency antibody recovery. It is
      further shown that recovered antibodies are functional and compatible with
      downstream applications. 

PMID- 26316181
TI  - Systematic review and meta-analysis on the significance of salvage esophagectomy
      for persistent or recurrent esophageal squamous cell carcinoma after definitive
      chemoradiotherapy.
AB  - The therapeutic strategy to be recommended in case of recurrent or persistent
      squamous cell esophageal cancer after completed definitive chemoradiotherapy
      (dCRT) has to be documented. Salvage esophagectomy has traditionally been
      recognized as a viable option, but many clinicians oppose the use of surgery due
      to the associated excessive morbidity and mortality. 'Second-line'
      chemoradiotherapy (CRT) without surgery may offer a treatment alternative in
      these difficult and demanding clinical situations. Until now, no comprehensive
      attempt has been carried out to compare the respective therapeutic options. A
      systematic literature search was performed focusing on studies comparing survival
      and treatment-related mortality in patients submitted to salvage esophagectomy or
      second-line CRT for recurrent or persistent esophageal squamous cell carcinoma
      after dCRT. Hazard ratios and risk ratios were calculated to compare the effect
      of these therapeutic strategies on overall survival and treatment-related
      mortality, respectively. Four studies containing 219 patients, with persistent or
      recurrent esophageal squamous cell carcinoma after dCRT, were included in the
      meta-analysis. The analysis revealed an overall survival benefit following
      salvage esophagectomy with a pooled hazard ratio for death of 0.42 (95%
      confidence interval 0.21-0.86, P = 0.017) compared with second-line CRT. A
      treatment-related mortality of 10.3% was recorded in the 36 patients who were
      submitted to salvage esophagectomy, while it was impossible to perform a meta
      analysis comparing treatment-related mortality between the groups. Salvage
      esophagectomy offers significant gain in long-term survival compared with second
      line CRT, although the surgery is potentially at a price of a high treatment
      related mortality.

PMID- 26316182
TI  - Can we judge an oxide by its cover? The case of platinum over alpha-Fe2O3 from
      first principles.
AB  - Metal/metal-oxide interfaces appear in a wide variety of disciplines including
      electronics, corrosion, electrochemistry, and catalysis. Specifically, covering a
      metal-oxide with a metal is often thought to enhance solar energy absorption and
      to improve photocatalytic activity. For example, the platinum/hematite (Pt/alpha
      Fe2O3) interface has demonstrated improved functionality. In order to advance our
      understanding of how metal coverage over an oxide helps performance, we
      characterize the geometry and electronic structure of the Pt/alpha-Fe2O3
      interface. We investigate the interface using density functional theory +U, and
      find a stable crystallographic orientation relationship: Fe2O3(0001)[11[combining
      macron]00]?Pt(111)[101[combining macron]] that agrees with experiment.
      Furthermore, there are significant changes in the electronic structure of alpha
      Fe2O3 as a result of Pt coverage. We therefore suggest the concept of "judging"
      the electronic properties of an oxide only with its cover. Specifically, covering
      Fe2O3 with Pt reduces carrier effective mass and creates a continuum of states in
      the band gap. The former could be beneficial for catalytic activity, while the
      latter may cause surface recombination. In order to circumvent this problem, we
      suggest putting metal coverage behind the oxide and far from the electrolyte in a
      photoelectrochemical device in order to quickly collect electron carriers and
      avoid recombination with vulnerable holes accumulating as a result of catalysis
      at the surface. 

PMID- 26316183
TI  - The medical autopsy as quality assurance tool in clinical medicine: dreams and
      realities.
AB  - The purpose of medical autopsy has changed to issues of quality assurance today.
      In addition, autopsies are considered valuable in medical education, e.g.,
      delivering cases for problem-based learning for students. Many studies underscore
      the need for autopsies also in the era of technical progress emphasizing the
      continuing discrepancies between antemortem and post mortem diagnoses. Despite
      these important tasks, we face a decline of autopsy for several reasons with
      complex interactions. The role of all persons involved in this decline is
      evaluated and suggestions for changes are proposed. Last but not least, the
      future of the autopsy is in the hands of pathology itself. 

PMID- 26316184
TI  - Does standardised structured reporting contribute to quality in diagnostic
      pathology? The importance of evidence-based datasets.
AB  - Key quality parameters in diagnostic pathology include timeliness, accuracy,
      completeness, conformance with current agreed standards, consistency and clarity
      in communication. In this review, we argue that with worldwide developments in
      eHealth and big data, generally, there are two further, often overlooked,
      parameters if our reports are to be fit for purpose. Firstly, population-level
      studies have clearly demonstrated the value of providing timely structured
      reporting data in standardised electronic format as part of system-wide quality
      improvement programmes. Moreover, when combined with multiple health data sources
      through eHealth and data linkage, structured pathology reports become central to
      population-level quality monitoring, benchmarking, interventions and benefit
      analyses in public health management. Secondly, population-level studies,
      particularly for benchmarking, require a single agreed international and evidence
      based standard to ensure interoperability and comparability. This has been taken
      for granted in tumour classification and staging for many years, yet
      international standardisation of cancer datasets is only now underway through the
      International Collaboration on Cancer Reporting (ICCR). In this review, we
      present evidence supporting the role of structured pathology reporting in quality
      improvement for both clinical care and population-level health management.
      Although this review of available evidence largely relates to structured
      reporting of cancer, it is clear that the same principles can be applied
      throughout anatomical pathology generally, as they are elsewhere in the health
      system. 

PMID- 26316186
TI  - A cross-sectional study on peripheral arterial disease in a district of Sri
      Lanka: prevalence and associated factors.
AB  - BACKGROUND: Peripheral arterial disease (PAD), a slowly progressive
      atherosclerotic disease affecting vital organs of the body, is increasingly
      recognized as a health burden worldwide. Epidemiological information on
      peripheral arterial disease is scarce in Sri Lanka. The present study intended to
      estimate the prevalence and associated factors of PAD among adults aged 40-74
      years in Gampaha district, Sri Lanka. METHODS: A cross-sectional study was
      carried out to estimate the prevalence of PAD among adults aged 40-74 years in
      four randomly selected divisional secretariat areas in Gampaha district in 2012
      2013. The sample size of 2912 adults was obtained from 104 clusters using
      multistage probability proportionate to size sampling. The number of individuals
      to be included in the 5-year age groups between 40 and 74 years was determined
      based on the population proportion of the respective age groups in the district.
      Cluster size was 28, and equal numbers of males and females were selected for
      each age group per cluster. PAD was defined as having an ankle-brachial pressure
      index <= 0.89. RESULTS: The age-and sex-standardized prevalence of PAD, adjusted
      for the sensitivity of the ankle-brachial pressure index was 3.6% (95% CI 2.9
      4.3%), and no significant difference was found between males (3.7%) and females
      (3.6%) (p = 0.08). Eighty-eight individuals were newly identified as having PAD,
      and a significant trend of prevalence with increasing age was observed (p <
      0.001). Histories of diabetes mellitus, hypertension, dyslipidemia, coronary
      artery disease, cerebrovascular accident, smoking, and erectile dysfunction among
      males were significantly associated with PAD (p < 0.001). Only one third of those
      with PAD experienced claudication symptoms. CONCLUSIONS: PAD was found to be a
      hidden disease in the Gampaha district population. Although there is minimal
      attention on PAD at present, the disease is likely to become a problematic public
      health concern in Sri Lanka, particularly with its aging population. Primary
      prevention measures to modify risk factors of PAD, including screening activities
      for early identification, should be a priority.

PMID- 26316185
TI  - Toxicity of zinc oxide nanoparticles on adult male Wistar rats.
AB  - The purpose of this study was to investigate the effects of zinc oxide
      nanoparticles (nZnO) on adult male Wistar rats. Thirty male Wistar rats divided
      into five groups of six animals each were used for this study. For ten days,
      Groups one to four continuously received 50, 100, 150 and 200 mg/kg nZnO,
      respectively. Group five served as the control group. At the end of the study,
      the rats were sacrificed and histopathological study of the liver and renal
      tissue, sperm analysis, serum oxidative stress parameters and some liver enzymes
      were done. The results of this study showed that nZnO at concentration more than
      50 mg/kg lead to significant changes in liver enzymes, oxidative stress, liver
      and renal tissue and sperm quality and quantity. In conclusion, the toxicity of
      nZnO is more significant when the concentration is increased; however, the use of
      low doses requires further investigation.

PMID- 26316188
TI  - Hepatic Resection for Hepatocellular Carcinoma with Tumor Thrombus in the Major
      Portal Vein.
AB  - BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) with tumor thrombus
      in the major portal vein has been extremely poor. We investigated the outcome of
      hepatic resection in HCC with major portal vein tumor thrombus (PVTT). METHODS:
      We retrospectively evaluated 52 consecutive patients who underwent hepatic
      resection for HCC with tumor thrombi in the first branch or trunk of the portal
      vein. Factors related to disease-free survival (DFS) and overall survival (OS)
      were analyzed. RESULTS: The median DFS and OS times were 8.9 and 27.6 months for
      the whole cohort, respectively. Multiple tumors (hazard ratio 2.12; 95% CI 1.11
      4.33; p = 0.023), positive surgical margins (hazard ratio 2.45; 95% CI 1.19-4.81;
      p = 0.016), and non-adjuvant hepatic arterial infusion chemotherapy (HAIC; hazard
      ratio 2.07; 95% CI 1.11-3.90; p = 0.023) were independent risk factors for DFS.
      Non-adjuvant HAIC (hazard ratio 1.84; 95% CI 1.01-3.37; p = 0.047) was an
      independent risk factor for OS. CONCLUSIONS: Macroscopically curative resection
      seems to be of benefit to HCC patients with PVTT, even with tumor thrombi in the
      first branch or trunk of the portal vein. Adjuvant postoperative HAIC might
      improve DFS and OS in such patients.

PMID- 26316187
TI  - Monoamine Oxidase-A Occupancy by Moclobemide and Phenelzine: Implications for the
      Development of Monoamine Oxidase Inhibitors.
AB  - BACKGROUND: Monoamine oxidase inhibitors (MAOIs) are being developed for major
      depressive disorder, Alzheimer's, and Parkinson's Disease. Newer MAOIs have
      minimal sensitivity to tyramine, but a key limitation for optimizing their
      development is that standards for in vivo monoamine oxidase-A (MAO-A) occupancy
      in humans are not well established. The objectives were to determine the dose
      occupancy relationship of moclobemide and the occupancy of phenelzine at typical
      clinical dosing. METHODS: Major depressive episode (MDE) subjects underwent
      [(11)C]harmine positron emission tomography scanning prior to and following 6
      weeks of treatment with moclobemide or phenelzine. RESULTS: Mean brain MAO-A
      occupancies were 74.23+/-8.32% for moclobemide at 300-600 mg daily (n = 11),
      83.75+/-5.52% for moclobemide at 900-1200 mg daily (n = 9), and 86.82+/-6.89% for
      phenelzine at 45-60 mg daily (n = 4). The regional dose-occupancy relationship of
      moclobemide fit a hyperbolic function [F(x) = a(x/[b + x]); F(1,18) = 5.57 to
      13.32, p = 0.002 to 0.03, mean 'a': 88.62+/-2.38%, mean 'b': 69.88+/-4.36 mg].
      Multivariate analyses of variance showed significantly greater occupancy of
      phenelzine (45-60mg) and higher-dose moclobemide (900-1200 mg) compared to lower
      dose moclobemide [300-600 mg; F(7,16) = 3.94, p = 0.01]. CONCLUSIONS: These
      findings suggest that for first-line MDE treatment, daily moclobemide doses of
      300-600mg correspond to a MAO-A occupancy of 74%, whereas for treatment-resistant
      MDE, either phenelzine or higher doses of moclobemide correspond to a MAO-A
      occupancy of at least 84%. Therefore, novel MAO inhibitor development should aim
      for similar thresholds. The findings provide a rationale in treatment algorithm
      design to raise moclobemide doses to inhibit more MAO-A sites, but suggest
      switching from high-dose moclobemide to phenelzine is best justified by binding
      to additional targets.

PMID- 26316189
TI  - Spinal hamartoma in an elderly man.
AB  - Spinal hamartoma is a very rare, benign spinal lesion, usually occurring in
      children with either spinal dysraphism or neurofibromatosis type 1. We report a
      case of thoracic spinal hamartoma in a 75-year-old male without associated
      lesions. This patient represents the oldest of 19 patients whose cases we found
      reported in detail and one of only nine reported cases without associated
      lesions. On magnetic resonance imaging, the current patient showed a well-defined
      exophytic appearance arising from the dorsal midline surface of the spinal cord.
      We discuss the radiological and pathological features of spinal hamartoma and
      review the literature, focusing on magnetic resonance imaging features for
      diagnosing spinal hamartoma. 

PMID- 26316190
TI  - Multi-Layer and Recursive Neural Networks for Metagenomic Classification.
AB  - Recent advances in machine learning, specifically in deep learning with neural
      networks, has made a profound impact on fields such as natural language
      processing, image classification, and language modeling; however, feasibility and
      potential benefits of the approaches to metagenomic data analysis has been
      largely under-explored. Deep learning exploits many layers of learning nonlinear
      feature representations, typically in an unsupervised fashion, and recent results
      have shown outstanding generalization performance on previously unseen data.
      Furthermore, some deep learning methods can also represent the structure in a
      data set. Consequently, deep learning and neural networks may prove to be an
      appropriate approach for metagenomic data. To determine whether such approaches
      are indeed appropriate for metagenomics, we experiment with two deep learning
      methods: i) a deep belief network, and ii) a recursive neural network, the latter
      of which provides a tree representing the structure of the data. We compare these
      approaches to the standard multi-layer perceptron, which has been well
      established in the machine learning community as a powerful prediction algorithm,
      though its presence is largely missing in metagenomics literature. We find that
      traditional neural networks can be quite powerful classifiers on metagenomic data
      compared to baseline methods, such as random forests. On the other hand, while
      the deep learning approaches did not result in improvements to the classification
      accuracy, they do provide the ability to learn hierarchical representations of a
      data set that standard classification methods do not allow. Our goal in this
      effort is not to determine the best algorithm in terms accuracy-as that depends
      on the specific application-but rather to highlight the benefits and drawbacks of
      each of the approach we discuss and provide insight on how they can be improved
      for predictive metagenomic analysis. 

PMID- 26316191
TI  - Development of an Immunosensor Based on Layered Double Hydroxides for MMR Cancer
      Biomarker Detection.
AB  - As a potential biomarker for the investigation of cancer inflammatory profiles,
      macrophage mannose receptor (MMR, CD206) is herein selected to develop an
      immunosensor based on layered double hydroxide (LDH). Like an endocyte C-type
      lectin receptor, MMR plays an important role in immune homeostasis by scavenging
      unwanted mannose glycoproteins. It attracts a progressive attention thanks to its
      particularly high expression within the tumor microenvironment. There is a great
      of interest to develop an immunosensor based on an antibody specific to MMR for
      detection of stroma versus tumor cells. In this work, we studied the feasibility
      of high sensitive MMR cancer Screen Printed Electrode (SPE) immunosensor. Working
      electrode of commercialized SPE was modified by immobilization of specific
      antibody (anti-MMR) into thin layer of LDH nanomaterials. Structural,
      morphological, and surface properties of LDHs were studied by X-Ray diffraction,
      atomic force microscopy and Infrared spectroscopy in ATR. Cyclic Voltammetry
      technique was used to study interaction between the human recombinant MMR protein
      (rHu-MMR, NSO derived) and an immobilized antibody into developed immunosensor.
      High specific response of -11.72 MUA/ng.mL(-1) (with a correlation coefficient of
      R(2)=0.994 ) were obtained in linear range of 0.05 ng/mL to 10.0 ng/mL of
      specific recombinant antigen. The limit of detection (LOD) was less than 15.0
      pg/mL. From these attractive results, the feasibility of an electrochemical
      immunosensor for cancer was proved. Additional experiments to study stability and
      reproducibility the immunosensor should be completed in perspective to use these
      anti-MMR based immunosensors for sensing human MMR in patient biopsies and sera. 

PMID- 26316192
TI  - A New Thermal Conductivity Model With Shaped Factor Ferromagnetism Nanoparticles
      Study for the Blood Flow in Non-Tapered Stenosed Arteries.
AB  - Blood flow model is consider to study the influence of magnetic field and
      different shaped nanoparticles in non-tapered stenosed arteries. The metallic
      different shaped nanoparticles for the blood flow with water as base fluid is not
      explored so far. The representation for the blood flow is through an axially and
      radially symmetric stenosis. Symmetry of the distribution of the wall shearing
      stress and resistive impedance and their growth with the developing stenosis is
      another important feature of our analysis. Exact solutions have been evaluated
      for velocity, resistance impedance, wall shear stress and shearing stress at the
      stenosis throat. The graphical results of different type of tapered arteries
      (i.e., converging tapering) have been examined for different parameters of
      interest for Cu-water. 

PMID- 26316193
TI  - Physiological and Genetic Analyses of Arabidopsis Thaliana Growth Responses to
      Electroporation.
AB  - Stress-induced effect on Arabidopsis thaliana seeds due to high-intensity
      electrical pulses is described. The pulsed electric field (PEF) treatment system
      was constructed under the concept of electroporation to deliver 10-nanosecond, 5
      Hz pulse train with the energy density per pulse up to 4 kJ .kg (-1). The
      analysis of the growth responses revealed that the optimal specific energy of  ~ 
      1 kJ . kg (-1) delivered the positive effect on the early growth with significant
      enhancement in the germination percentage and leaf area expansion. The same
      treatment energy, in addition, contributed to the higher level of the gene
      expression at nearly tenfold (PAD3 and PR1) compared with untreated control. Such
      optimistic evidences suggest that the PEF treatment may have practical
      applications such as to stimulate the delayed germination in preserved economical
      crops and should be preferred over chemical treatments due to its short-term
      effect. 

PMID- 26316194
TI  - Pilot Randomized Controlled Trial of Internet-Delivered Cognitive-Behavioral
      Treatment for Pediatric Headache.
AB  - OBJECTIVE: To evaluate the feasibility and preliminary effectiveness of an
      Internet-delivered cognitive-behavioral therapy (CBT) intervention for
      adolescents with chronic headache. BACKGROUND: Headache is among the most common
      pain complaints of childhood. Cognitive-behavioral interventions are efficacious
      for improving pain among youth with headache. However, many youth do not receive
      psychological treatment for headache due to poor access, which has led to
      consideration of alternative delivery modalities such as the Internet. METHODS:
      We used a parallel arm randomized controlled trial design to evaluate the
      feasibility and preliminary effectiveness of an Internet-delivered family-based
      CBT intervention, Web-based management of adolescent pain. Adolescents were
      eligible for the trial if they were a new patient being evaluated in a
      specialized headache clinic, between 11 and 17 years of age, and had recurrent
      headache for 3 months or more as diagnosed by a pediatric neurologist. Eighty
      three youths were enrolled in the trial. An online random number generator was
      used to randomly assign participants to receive Internet CBT adjunctive to
      specialized headache treatment (n = 44) or specialized headache treatment alone
      (n = 39). The primary treatment outcome was headache days. RESULTS: Youth and
      parents in the Internet CBT group demonstrated high levels of engagement with the
      web program and reported satisfaction with the intervention. Multilevel modelling
      (MLM) was used to conduct hypothesis testing for continuous outcomes. For our
      primary treatment outcome of headache days, adolescents reported a statistically
      significant reduction in headache days from baseline to post-treatment and
      baseline to 3-month follow-up in both treatment conditions (main effect for time
      F(2, 136) = 19.70, P < .001). However, there was no statistically significant
      difference between the Internet CBT group and the specialized headache treatment
      group at post-treatment or follow-up (group * time interaction F(2, 134) = 0.94,
      P = .395). For our secondary treatment outcomes, findings from MLM showed that
      adolescents in both groups demonstrated statistically significant improvement
      headache pain intensity, activity limitations, depressive symptoms, and parent
      protective behaviors from baseline to post-treatment and these gains were
      maintained at 3-month follow-up. Adolescent anxiety symptoms and sleep did not
      change during the study period for either group. There were no statistically
      significant group differences on any secondary outcomes at post-treatment or
      follow-up (P > .05 for all outcomes). No adverse events were reported.
      CONCLUSION: Although adjunctive Internet CBT did not lead to additional benefit
      in this population, future research should evaluate whether it is an effective
      intervention for adolescents with headache who are unable to access specialized
      headache treatment.

PMID- 26316195
TI  - Effects of Fe deficiency on the protein profile of Brassica napus phloem sap.
AB  - The aim of this work was to study the effect of Fe deficiency on the protein
      profile of phloem sap exudates from Brassica napus using 2DE (IEF-SDS-PAGE). The
      experiment was repeated thrice and two technical replicates per treatment were
      done. Phloem sap purity was assessed by measuring sugar concentrations. Two
      hundred sixty-three spots were consistently detected and 15.6% (41) of them
      showed significant changes in relative abundance (22 decreasing and 19
      increasing) as a result of Fe deficiency. Among them, 85% (35 spots), were
      unambiguously identified. Functional categories containing the largest number of
      protein species showing changes as a consequence of Fe deficiency were signaling
      and regulation (32%), and stress and redox homeostasis (17%). The Phloem sap
      showed a higher oxidative stress and significant changes in the hormonal profile
      as a result of Fe deficiency. Results indicate that Fe deficiency elicits major
      changes in signaling pathways involving Ca and hormones, which are generally
      associated with flowering and developmental processes, causes an alteration in
      ROS homeostasis processes, and induces decreases in the abundances of proteins
      involved in sieve element repair, suggesting that Fe-deficient plants may have an
      impaired capacity to heal sieve elements upon injury. 

PMID- 26316196
TI  - Religiosity, Social Support and Care Associated with Health in Older Mexicans
      with Diabetes.
AB  - The main purpose of this study was to examine the relationships between
      religiosity, social support, diabetes care and control and self-rated health of
      people living in Mexico who have been diagnosed with diabetes. Structural
      equation modeling was used to examine these associations using the Mexican Health
      and Aging Study, a national representative survey of older Mexicans. Findings
      indicate that emotional support from one's spouse/partner directly affects
      diabetes care and control and health. Although there is no direct relationship
      between religiosity and health, religiosity was positively associated with
      diabetes care and control, but not significantly related to health. 

PMID- 26316197
TI  - A Report of Stiff Person Syndrome in Tanzania with First Epidemiological Figures
      for Sub-Saharan Africa.

PMID- 26316198
TI  - Association between dietary factors and plasma fetuin-A concentrations in the
      general population.
AB  - Circulating fetuin-A, a novel marker for hepatic fat accumulation, has been
      related to a higher risk of type 2 diabetes and cardiovascular diseases in a
      growing number of prospective studies. However, little is known about dietary
      determinants of fetuin-A concentrations in the general population. Therefore, we
      aimed to investigate the association between dietary intake of energy, energy
      providing nutrients, alcohol and major food groups and plasma fetuin-A
      concentrations in the Bavarian Food Consumption Survey II. Dietary intake was
      assessed by three 24-h dietary recalls, and plasma concentrations of fetuin-A
      were measured in 558 adults (18-81 years). After multivariable adjustment for
      lifestyle factors and body fatness, higher energy intake was nonsignificantly
      associated with higher fetuin-A concentrations (per 2092 kJ/d (500 kcal/d) 3.7
      ug/ml, 95 % CI -0.5, 7.8 ug/ml). There was no clear association between energy
      providing nutrients and fetuin-A concentrations. Higher alcohol intake was
      associated with lower fetuin-A concentrations (P trend 0.003): mean fetuin-A
      concentrations were 324 (95 % CI 313, 335) ug/ml in non-drinkers, and with 293
      (95 % CI 281, 306) ug/ml significantly lower in participants who drank >=30 g
      alcohol per d. Mean fetuin-A concentrations decreased across quintiles of milk
      and dairy product intake (lowest quintile 319 (95 % CI 309, 330) ug/ml; highest
      quintile 304 (95 % CI 293, 314) ug/ml; P trend 0.03), and each 150-g increment in
      milk/dairy products per d was associated with 5.6 (95 % CI -9.6, -1.5) ug/ml
      lower fetuin-A. Dietary intakes of vegetables, meat or fish were not associated
      with fetuin-A concentrations. Because of the preventive potential of our
      findings, further exploration is warranted. 

PMID- 26316199
TI  - Hypoglycemia in a diabetic patient during hepatitis C therapy.

PMID- 26316200
TI  - First report on the isolation of melittin from Iranian honey bee venom and
      evaluation of its toxicity on gastric cancer AGS cells.
AB  - BACKGROUND: It has been previously reported that melittin, the main ingredient of
      honey bee venom, has anticancer properties. However, there appears to be no
      earlier study focusing on the isolation of melittin from Iranian honey bee venom
      (Apis mellifera meda), and evaluation of its effect on cancerous cells. METHODS:
      We isolated melittin using reversed-phase high performance liquid chromatography,
      and its potential toxicity on gastric cancer AGS cells was determined with an MTT
      [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] assay.
      Furthermore, to ascertain whether melittin induces apoptosis or necrosis in these
      cells, morphological evaluation, DNA fragmentation assay, propidium podide and
      annexin-V-FITC dual staining, and flow cytometric analysis were also conducted.
      RESULTS: The results of our study suggested that melittin inhibited the
      proliferation of AGS cells in a dose and time-dependent trend. All of the above
      four distinct assays indicated that melittin induces necrosis in AGS cells at
      concentrations of >= 1 MUg/mL. CONCLUSION: The present study indicated that
      melittin has an anticancer effect on gastric cancer AGS cells and stimulates
      necrotic cell death in these cells.

PMID- 26316201
TI  - Adult-onset glutaric aciduria type I presenting with white matter abnormalities
      and subependymal nodules.
AB  - A 55-year-old female presented with a 6-year history of paresthesias,
      incontinence, spasticity, and gait abnormalities. Neuroimaging revealed white
      matter abnormalities associated with subependymal nodules. Biochemical evaluation
      noted increased serum C5-DC glutarylcarnitines and urine glutaric and 3
      hydroxyglutaric acids. Evaluation of the glutaryl-CoA dehydrogenase (GCDH) gene
      revealed compound heterozygosity consisting of a novel variant (c.1219C>G;
      p.Leu407Val) and pathogenic mutation (c.848delT; p.L283fs). Together, these
      results were consistent with a diagnosis of adult-onset type I glutaric aciduria.

PMID- 26316202
TI  - Available Tools to Facilitate Early Patient Access to Medicines in the EU and the
      USA: Analysis of Conditional Approvals and the Implications for Personalized
      Medicine.
AB  - Scientific knowledge and our understanding of the human body and diseases have
      limited any possible treatment tailoring to each patient. The technological
      advances enabling the integration of various data sets (e.g. '-omics',
      microbiome, epigenetics and environmental exposure) have facilitated a greater
      understanding of the human body, the molecular basis of disease and all the
      factors influencing disease onset, progression and response to treatment, thereby
      ushering in the era of personalized medicine. We evaluate the regulatory
      approaches available to facilitate early patient access to efficacious and safe
      compounds in the EU and the USA in order to make more informed recommendations in
      the future as to the gaps in regulations for early patient access. An in-depth
      analysis of conditional approvals (EU) and accelerated approvals (USA) is
      performed based on the publicly available information (European public assessment
      reports and a summary review of products approved under both programmes). The
      types of product, indications, time to approval and type of evidence submitted
      were analysed. Between 2007 and early 2015, 17 products were conditionally
      approved in the EU and 25 in the USA, most of them in the area of oncology and
      based on evidence from phase II clinical trial data. Early approval of promising
      products based on data from early phases of development is already possible in
      the EU and the USA. Some of the improvements could entail implementing a rolling
      assessment of evidence in Europe and extending the scope of early dialogues. 

PMID- 26316203
TI  - Chirality control of self-assembled achiral nanofibers using amines in their
      solid state.
AB  - Although there are numerous examples of helical and spiral conformations in
      nature, including plant tendrils, snail shells, and even collagen, the occurrence
      of supramolecular systems that are able to reversibly undergo solid-to-solid
      helical transformation based on environmental chiral triggers is rare. In this
      work, we present a supramolecular, non-helical nanofiber which shows a distinct
      helical rearrangement in the presence of specific diamines and monoamines, such
      as cyclohexanediamines, alanine, lysine, and phenylalanine, depending on the
      molecular chirality of the surrounding analytes. A detailed investigation on the
      structural organization of the nanofibers using SEM and CD spectra analysis
      confirmed the repeatable and reversible nature of this amplification of chiral
      information. Further preparation of an electrospun nanofiber film was
      demonstrated for distinguishing chiral diamines and monoamines in solution by
      film immersion and CD analysis, which is the first example of amplification of
      chiral information in the solid-state using electrospun nanofiber films. With
      this system, we could demonstrate a reusable means for detecting the molecular
      chirality, which also provided a unique example of reversible control of solid
      state rearrangement in supramolecular helicity. 

PMID- 26316204
TI  - Metastasis suppressor 1 expression in human ovarian cancer: The impact on
      cellular migration and metastasis.
AB  - Metastasis suppressor 1 (MTSS1) is a potential metastasis suppressor gene
      involved in the regulation of cytoskeleton dynamics and subsequently in cell
      motility. MTSS1 expression is frequently reduced in a variety of cancer cells and
      tissues and this loss may account for increased invasive traits in cancer cells.
      The present study aimed to assess the role of MTSS1 in epithelial ovarian cancer
      (EOC) cells. Expression of MTSS1 in human ovarian cells was assessed at both the
      mRNA and protein levels using reverse transcription-PCR (RT-PCR) and
      immunohistochemistry, respectively. Full-length MTSS1 cDNA expression vector was
      used to generate MTSS1 overexpressing cells. The effect of MTSS1 overexpression
      on cellular functions was examined in EOC cells using a variety of in vitro
      assays. MTSS1 expression was observed both in ovarian cancer tissues and EOC
      cells. Over-expression of MTSS1 protein reduced the growth, invasion, adhesion
      and migration of EOC cell lines in vitro. The present study revealed that MTSS1
      plays an essential inhibitory role in the development and progression of ovarian
      cancers. MTSS1 overexpression is intimately related to migration and metastasis,
      suggesting that MTSS1 is a potential prognostic marker and therapeutic molecular
      target in human ovarian cancer.

PMID- 26316205
TI  - Impact of nephrolithiasis on kidney function.
AB  - BACKGROUND: Kidney stone disease has been associated with reduced kidney function
      and chronic kidney disease (CKD). The objective of the study was to examine
      kidney function, body mass index (BMI) and the prevalence of cardiovascular
      disease, hypertension and diabetes in recurrent kidney stone formers. METHODS: A
      cross-sectional, case-control study comparing measures of kidney function, BMI
      and comorbid conditions was conducted in 195 kidney stone patients aged 18 to 70
      years with recurrent clinical stone events and 390 age- and gender-matched
      controls. Wilcoxon-Mann-Whitney, chi-square tests and analysis of covariance were
      used to compare serum creatinine (SCr) and estimated glomerular filtration rate
      (eGFR) between the groups. RESULTS: The median age of stone formers was 51
      (range, 19-70) years and 108 (55 %) were males. Seventy patients (36 %) had
      experienced 2-4 clinical stone events, 41 (21 %) 5-10 episodes and 84 (43 %) more
      than 10. The median SCr was 75 (41-140) MUmol/L in the stone formers and 64 (34
      168) MUmol/L in the control group (p < 0.001). The mean eGFR was 87 +/- 20 and
      104 +/- 22 mL/min/1.73 m(2) in the stone formers and controls, respectively (p <
      0.001). After adjustment for body size and comorbid conditions, the difference in
      SCr and eGFR between cases and controls remained highly significant (p < 0.001).
      The prevalence of CKD was 9.3 % among stone formers compared with 1.3 % in the
      control group (P < 0.001). Hypertension and diabetes were significantly more
      prevalent among the cases that also had higher BMI than controls. CONCLUSIONS:
      Recurrent kidney stone formers have a significantly lower level of kidney
      function and a markedly higher prevalence of CKD than age- and gender-matched
      control subjects. The observed deleterious effect of kidney stones on kidney
      function appears to be independent of comorbid conditions.

PMID- 26316207
TI  - Partial Aneurysmectomy of Venous Aneurysms in Arteriovenous Dialysis Fistulas.
AB  - Upper extremity native arteriovenous fistulas (AVFs) continue to be the standard
      of care for hemodialysis patient's access. Although autogenous fistulas are
      superior to catheters and synthetic grafts, they are not without their own
      complications. One complication is venous aneurysms that can lead to skin
      erosion, bleeding, and site loss. Although traditionally repaired with ligation,
      interposition grafts, or stent placement, in this article, we discuss our
      experience with aneurysmorrhaphy utilizing a thoracoabdominal (TA) stapler.
      Thirteen aneurysms were treated with the TA stapler at a single, nonuniversity
      hospital for all patients from 2012 to 2014. The average aneurysm diameter was
      3.6 cm, and the average fistula age was 57.9 months. There were no bleeding
      complications or recurrences. The primary patency was 80% at 6 months, with a
      primary assisted patency of 90% during the same time frame. Aneurysmorrhaphy with
      the TA stapler appears to be a safe and viable option for the treatment of venous
      aneurysms associated with AVFs. 

PMID- 26316208
TI  - Catalysis of an Essential Step in Vitamin B2 Biosynthesis by a Consortium of
      Broad Spectrum Hydrolases.
AB  - An enzyme catalysing the essential dephosphorylation of the riboflavin precursor,
      5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione 5'-phosphate (6), was purified
      about 800-fold from a riboflavin-producing Bacillus subtilis strain, and was
      assigned as the translation product of the ycsE gene by mass spectrometry. YcsE
      is a member of the large haloacid dehalogenase (HAD) superfamily. The recombinant
      protein was expressed in Escherichia coli. It catalyses the hydrolysis of 6 (vmax
      , 12 MUmol mg(-1)  min(-1) ; KM , 54 MUm) and of FMN (vmax , 25 MUmol mg(-1) 
      min(-1) ; KM , 135 MUm). A ycsE deletion mutant of B. subtilis was not riboflavin
      dependent. Two additional proteins (YwtE, YitU) that catalyse the hydrolysis of 6
      at appreciable rates were identified by screening 13 putative HAD superfamily
      members from B. subtilis. The evolutionary processes that have resulted in the
      handling of an essential step in the biosynthesis of an essential cofactor by a
      consortium of promiscuous enzymes require further analysis.

PMID- 26316206
TI  - International Veterinary Epilepsy Task Force's current understanding of
      idiopathic epilepsy of genetic or suspected genetic origin in purebred dogs.
AB  - Canine idiopathic epilepsy is a common neurological disease affecting both
      purebred and crossbred dogs. Various breed-specific cohort, epidemiological and
      genetic studies have been conducted to date, which all improved our knowledge and
      general understanding of canine idiopathic epilepsy, and in particular our
      knowledge of those breeds studied. However, these studies also frequently
      revealed differences between the investigated breeds with respect to clinical
      features, inheritance and prevalence rates. Awareness and observation of breed
      specific differences is important for successful management of the dog with
      epilepsy in everyday clinical practice and furthermore may promote canine
      epilepsy research. The following manuscript reviews the evidence available for
      breeds which have been identified as being predisposed to idiopathic epilepsy
      with a proven or suspected genetic background, and highlights different breed
      specific clinical features (e.g. age at onset, sex, seizure type), treatment
      response, prevalence rates and proposed inheritance reported in the literature.
      In addition, certain breed-specific diseases that may act as potential
      differentials for idiopathic epilepsy are highlighted. 

PMID- 26316209
TI  - A 1.26 MUW Cytomimetic IC Emulating Complex Nonlinear Mammalian Cell Cycle
      Dynamics: Synthesis, Simulation and Proof-of-Concept Measured Results.
AB  - Cytomimetic circuits represent a novel, ultra low-power, continuous-time,
      continuous-value class of circuits, capable of mapping on silicon cellular and
      molecular dynamics modelled by means of nonlinear ordinary differential equations
      (ODEs). Such monolithic circuits are in principle able to emulate on chip, single
      or multiple cell operations in a highly parallel fashion. Cytomimetic topologies
      can be synthesized by adopting the Nonlinear Bernoulli Cell Formalism (NBCF), a
      mathematical framework that exploits the striking similarities between the
      equations describing weakly-inverted Metal-Oxide Semiconductor (MOS) devices and
      coupled nonlinear ODEs, typically appearing in models of naturally encountered
      biochemical systems. The NBCF maps biological state variables onto strictly
      positive subthreshold MOS circuit currents. This paper presents the synthesis,
      the simulation and proof-of-concept chip results corresponding to the emulation
      of a complex cellular network mechanism, the skeleton model for the network of
      Cyclin-dependent Kinases (CdKs) driving the mammalian cell cycle. This five
      variable nonlinear biological model, when appropriate model parameter values are
      assigned, can exhibit multiple oscillatory behaviors, varying from simple
      periodic oscillations, to complex oscillations such as quasi-periodicity and
      chaos. The validity of our approach is verified by simulated results with
      realistic process parameters from the commercially available AMS 0.35 MUm
      technology and by chip measurements. The fabricated chip occupies an area of 2.27
      mm2 and consumes a power of 1.26 MUW from a power supply of 3 V. The presented
      cytomimetic topology follows closely the behavior of its biological counterpart,
      exhibiting similar time-dependent solutions of the Cdk complexes, the
      transcription factors and the proteins.

PMID- 26316211
TI  - Aspergillus and aspergilloses in wild and domestic animals: a global health
      concern with parallels to human disease.
AB  - The importance of aspergillosis in humans and various animal species has
      increased over the last decades. Aspergillus species are found worldwide in
      humans and in almost all domestic animals and birds as well as in many wild
      species, causing a wide range of diseases from localized infections to fatal
      disseminated diseases, as well as allergic responses to inhaled conidia. Some
      prevalent forms of animal aspergillosis are invasive fatal infections in sea fan
      corals, stonebrood mummification in honey bees, pulmonary and air sac infection
      in birds, mycotic abortion and mammary gland infections in cattle, guttural pouch
      mycoses in horses, sinonasal infections in dogs and cats, and invasive pulmonary
      and cerebral infections in marine mammals and nonhuman primates. This article
      represents a comprehensive overview of the most common infections reported by
      Aspergillus species and the corresponding diseases in various types of animals. 

PMID- 26316210
TI  - Early goal-directed resuscitation of patients with septic shock: current evidence
      and future directions.
AB  - Severe sepsis and septic shock are among the leading causes of mortality in the
      intensive care unit. Over a decade ago, early goal-directed therapy (EGDT)
      emerged as a novel approach for reducing sepsis mortality and was incorporated
      into guidelines published by the international Surviving Sepsis Campaign. In
      addition to requiring early detection of sepsis and prompt initiation of
      antibiotics, the EGDT protocol requires invasive patient monitoring to guide
      resuscitation with intravenous fluids, vasopressors, red cell transfusions, and
      inotropes. The effect of these measures on patient outcomes, however, remains
      controversial. Recently, three large randomized trials were undertaken to re
      examine the effect of EGDT on morbidity and mortality: the ProCESS trial in the
      United States, the ARISE trial in Australia and New Zealand, and the ProMISe
      trial in England. These trials showed that EGDT did not significantly decrease
      mortality in patients with septic shock compared with usual care. In particular,
      whereas early administration of antibiotics appeared to increase survival,
      tailoring resuscitation to static measurements of central venous pressure and
      central venous oxygen saturation did not confer survival benefit to most
      patients. In the following review, we examine these findings as well as other
      evidence from recent randomized trials of goal-directed resuscitation. We also
      discuss future areas of research and emerging paradigms in sepsis trials. 

PMID- 26316212
TI  - In vitro antifungal activity of antipsychotic drugs and their combinations with
      conventional antifungals against Scedosporium and Pseudallescheria isolates.
AB  - In the present study, in vitro antifungal activities of five antipsychotic drugs
      (i.e., chlorpromazine hydrochloride, CPZ; trifluoperazine hydrochloride, TPZ;
      amantadine hydrochloride; R-(-)-deprenyl hydrochloride, and valproic acid sodium
      salt) and five conventional antifungal drugs (i.e., amphotericin B, AMB;
      caspofungin, CSP; itraconazole; terbinafine, TRB and voriconazole, VRC) were
      investigated in broth microdilution tests against four clinical and five
      environmental Scedosporium and Pseudallescheria isolates. When used alone,
      phenothiazines CPZ and TPZ exerted remarkable antifungal effects. Thus, their in
      vitro combinations with AMB, CSP, VRC, and TRB were also examined against the
      clinical isolates. In combination with antifungal agents, CPZ was able to act
      synergistically with AMB and TRB in cases of one and two isolates, respectively.
      In all other cases, indifferent interactions were revealed. Antagonism was not
      observed between the tested agents. These combinations may establish a more
      effective and less toxic therapy after further in vitro and in vivo studies for
      Scedosporium and Pseudallescheria infections. 

PMID- 26316213
TI  - Novel in vivo observations on double acting points of luliconazole on
      Trichophyton rubrum: an ultrastructural study.
AB  - Scales from lesional skin of 12 patients with tinea pedis were investigated by
      scanning electron microscopy (SEM) and transmission electron microscopy (TEM) to
      gain an insight into the spatial and morphological changes of dermatophytes after
      application of a clinical dosage of topical luliconazole 1% cream (Lulicon(r)
      cream 1%). In all cases, Trichophyton rubrum was identified. The scales from the
      lesions collected before and after topical luliconazole application were fixed
      with glutaraldehyde and subjected to SEM and TEM. For SEM, fixed specimens were
      first placed in 1N-KOH and then post-fixed and observed. SEM showed a swollen
      appearance of fungal hyphae as an early change, and then shrinkage of them
      showing a flattened and twisted appearance as a later change. TEM showed cell
      wall alterations with initial development of and accumulation of a granular
      structure in the outermost layer and subsequent amorphous and electron-lucent
      change of the thickened inner part of the cell wall. This is the first report of
      dramatic morphological changes of T. rubrum before and after topical luliconazole
      application in vivo demonstrated by SEM and TEM. We hypothesize that luliconazole
      has double acting points, on the plasma membrane and cell wall, of dermatophyte
      hyphae.

PMID- 26316214
TI  - Working memory affects false memory production for emotional events.
AB  - Whereas a link between working memory (WM) and memory distortions has been
      demonstrated, its influence on emotional false memories is unclear. In two
      experiments, a verbal WM task and a false memory paradigm for negative, positive
      or neutral events were employed. In Experiment 1, we investigated individual
      differences in verbal WM and found that the interaction between valence and WM
      predicted false recognition, with negative and positive material protecting high
      WM individuals against false remembering; the beneficial effect of negative
      material disappeared in low WM participants. In Experiment 2, we lowered the WM
      capacity of half of the participants with a double task request, which led to an
      overall increase in false memories; furthermore, consistent with Experiment 1,
      the increase in negative false memories was larger than that of neutral or
      positive ones. It is concluded that WM plays a critical role in determining false
      memory production, specifically influencing the processing of negative material.

PMID- 26316215
TI  - Splenectomy for beta-Thalassemia Major in Resource Challenged Settings: Often a
      Hobson's Choice!

PMID- 26316216
TI  - Cervical Arthroplasty for Traumatic Disc Herniation: An Age- and Sex-matched
      Comparison with Anterior Cervical Discectomy and Fusion.
AB  - BACKGROUND: The efficacy and safety of using cervical arthroplasty for
      degenerative disc disease have been demonstrated by prospective, randomized and
      controlled clinical trials. However, there are scant data on using cervical
      arthroplasty for traumatic disc herniation. Therefore, this study aimed to
      investigate the outcomes of patients who underwent cervical arthroplasty for
      traumatic disc herniation. METHODS: This cohort included patients who were
      admitted through the emergency department for trauma. Only patients who had newly
      onset, one- or two-level cervical disc disease causing radiculopathy or
      myelopathy were identified. None of these patients had previously sought for
      medical attention for such problems. Those patients who had severe spinal cord
      injury (i.e. American Spinal Injury Association scale A, B or C) or severe
      myelopathy (i.e. Nurick scale 4 or 5), bony fracture, dislocation, perched facet,
      kyphotic deformity, or instability were also excluded. An age- and sex-matched
      one-to-one comparison was made between patients who underwent cervical
      arthroplasty, on the one hand, and anterior cervical discectomy and fusion
      (ACDF). RESULTS: A total of 30 trauma patients (15 in the arthroplasty group and
      15 in the ACDF group) were analyzed, with a mean follow-up of 29.6 months. The
      demographic data were similar. Post-operation, the arthroplasty group had
      significant improvement in VAS of neck and arm pain, JOA, and NDI when compared
      to their pre-operation status. Similarly, the ACDF group also improved
      significantly after the operation. There were no differences between the two
      groups in post-operative VAS neck and arm pain, and JOA scores. The arthroplasty
      group maintained a range of motion in the indexed levels and had better NDI
      scores at 6-months post-operation than the ACDF group. CONCLUSIONS: For selected
      patients (i.e. no spinal cord injury, no fracture, and no instability) with
      traumatic cervical disc herniation, cervical arthroplasty yields similar
      improvement in clinical outcomes to ACDF and preserves segmental mobility.

PMID- 26316217
TI  - Stability analysis of a model gene network links aging, stress resistance, and
      negligible senescence.
AB  - Several animal species are considered to exhibit what is called negligible
      senescence, i.e. they do not show signs of functional decline or any increase of
      mortality with age. Recent studies in naked mole rat and long-lived sea urchins
      showed that these species do not alter their gene-expression profiles with age as
      much as other organisms do. This is consistent with exceptional endurance of
      naked mole rat tissues to various genotoxic stresses. We conjectured, therefore,
      that the lifelong transcriptional stability of an organism may be a key
      determinant of longevity. We analyzed the stability of a simple genetic-network
      model and found that under most common circumstances, such a gene network is
      inherently unstable. Over a time it undergoes an exponential accumulation of gene
      regulation deviations leading to death. However, should the repair systems be
      sufficiently effective, the gene network can stabilize so that gene damage
      remains constrained along with mortality of the organism. We investigate the
      relationship between stress-resistance and aging and suggest that the unstable
      regime may provide a mathematical basis for the Gompertz "law" of aging in many
      species. At the same time, this model accounts for the apparently age-independent
      mortality observed in some exceptionally long-lived animals. 

PMID- 26316218
TI  - Successful ultrarapid cryopreservation of wild Iberian ibex (Capra pyrenaica)
      spermatozoa.
AB  - A method for cryopreserving wild ibex sperm at high cooling rates was developed.
      To design a freezing solution based on Tris, citric acid, and glucose (TCG), two
      preliminary experiments were performed using glycerol (GLY) and dimethyl
      sulfoxide (DMSO) at different concentrations (5%, 10%, 20%). The 10% GLY + 10%
      DMSO combination reduced (P < 0.05) frozen-thawed sperm motility, which reached a
      minimum when 20% GLY + 20% DMSO was used. In the second experiment, sperm
      tolerance to three sucrose concentrations was evaluated (100-mM sucrose, 300-mM
      sucrose, 500-mM sucrose). Frozen-thawed sperm motility and sperm viability
      decreased (P < 0.05) at concentrations above 300 mM. The ultrarapid cooling
      procedure finally used involved a TCG egg yolk (ey)-based extender with 100-mM
      sucrose, either alone or with 5% GLY with or without BSA. Two warming procedures
      (37  degrees C vs. 60  degrees C) were also evaluated. The TCG ey with 100-mM
      sucrose but without GLY/BSA returned the best sperm quality variables. Slow
      warming at 37  degrees C strongly affected (P < 0.05) sperm motility and
      viability in all groups. Sperm selection by density gradient centrifugation
      produced no motile sperm when slow warming was performed. In contrast, when fast
      warming was used, sperm selection increased (P < 0.05) percentage of motility,
      viability, and the percentage of sperms with intact acrosomes. Heterologous in
      vivo fertilization involving domestic goats was performed to evaluate the in vivo
      fertilization capacity of the ultrarapidly cooled cryopreserved sperm (in TCG-ey
      + 100 mM sucrose), with warming undertaken at 60  degrees C. Inseminations of
      domestic goats resulted in three pregnancies (3 of 16, 18.7% fertility). In
      conclusion, ibex spermatozoa are strongly sensitive to high concentrations of
      permeable cryoprotectants and sucrose. However, the combination of ultrarapid
      cooling, using TCG-ey + 100-mM sucrose, and fast warming at 60  degrees C,
      followed by sperm selection by density gradient centrifugation to collect the
      motile sperm, has a positive effect on sperm viability. 

PMID- 26316219
TI  - The effect of energy balance on the transcriptome of bovine granulosa cells at 60
      days postpartum.
AB  - Dairy cows expend great amounts of energy during the lactation peak to cope with
      milk production. A state of negative energy balance (NEB) was suggested as a
      cause for the suboptimal fertility observed during this period, via an
      interaction with ovarian function. The objective of this study was to identify
      the impact of NEB on gene expression in granulosa cells of dairy cows at 60 days
      postpartum and to suggest a potential treatment to improve ovarian function.
      Dairy cows at 60 days postpartum from 10 typical medium-sized farms were
      synchronized using a single injection of prostaglandin. Dominant follicles  were
      collected 42 hours later by transvaginal aspiration. Blood concentrations of beta
      hydroxybutyrate (BHB) on the day of aspiration were used to classify animals into
      two groups: severe NEB (high BHB, n = 12) and mild NEB (low BHB, n = 12). The
      transcriptomes of granulosa cells from both groups were contrasted using
      microarrays, and the differentially expressed genes were analyzed using Ingenuity
      Pathway Analysis to identify affected functions and potential upstream
      regulators. Genes linked with cellular organization (KRT4 and PPL), proliferation
      (TACSTD2), and fatty acids metabolism (VNN2) were downregulated in granulosa
      cells from animals with severe NEB. Several genes linked to decitabine, a
      hypomethylating agent, and with beta-estradiol, were downregulated in the severe
      NEB group. Numerous genes linked to vitamins A and D were also downregulated in
      this group of cows, suggesting a potential deficiency of these vitamins in dairy
      cows during the postpartum period. This study supports the idea that energy
      balance has an impact on follicular dynamics which could be detrimental to
      resumption of fertility after calving. 

PMID- 26316221
TI  - Feedback Controller Design for the Synchronization of Boolean Control Networks.
AB  - This brief investigates the partial and complete synchronization of two Boolean
      control networks (BCNs). Necessary and sufficient conditions for partial and
      complete synchronization are established by the algebraic representations of
      logical dynamics. An algorithm is obtained to construct the feedback controller
      that guarantees the synchronization of master and slave BCNs. Two biological
      examples are provided to illustrate the effectiveness of the obtained results.

PMID- 26316220
TI  - Correlates of Mandrax use and condom beliefs in preventing sexually transmitted
      infections among a cohort of South African prison inmates.
AB  - BACKGROUND: This study was designed to identify the extent to which self-reported
      Mandrax use impacts condom-use beliefs amongst South African prison inmates.
      METHODS: Participants were inmates from four prisons in the provinces of KwaZulu
      Natal and Mpumalanga. In total, 357 inmates participated in the parent study of
      which 121 are included in this analysis based on their self-reported use of
      Mandrax. The questionnaire was developed in English, translated into Zulu, and
      back translated into English. Age significantly predicted the use of Mandrax:
      younger prison inmates reported higher use. Linear regression analysis was
      conducted to determine whether the use of Mandrax was associated with length of
      incarceration and other demographic variables, as well as participants' self
      reported condom use beliefs behavior. RESULTS: Regression results indicated that
      two factors operationalizing condom-use beliefs were impacted by Mandrax use: 1)
      it is important to use condoms every time you have sex (p<0.01); 2) condoms work
      well to prevent the spread of HIV (p<0.02). Both factors were also inversely
      related to Mandrax use. CONCLUSION: STI prevention programs among prison inmates
      that seek to promote safer sex behaviors among men must address attitudes to
      condom use, specifically consistent and correct use of latex condoms and reducing
      substance misuse.

PMID- 26316222
TI  - Oversampling the Minority Class in the Feature Space.
AB  - The imbalanced nature of some real-world data is one of the current challenges
      for machine learning researchers. One common approach oversamples the minority
      class through convex combination of its patterns. We explore the general idea of
      synthetic oversampling in the feature space induced by a kernel function (as
      opposed to input space). If the kernel function matches the underlying problem,
      the classes will be linearly separable and synthetically generated patterns will
      lie on the minority class region. Since the feature space is not directly
      accessible, we use the empirical feature space (EFS) (a Euclidean space
      isomorphic to the feature space) for oversampling purposes. The proposed method
      is framed in the context of support vector machines, where the imbalanced data
      sets can pose a serious hindrance. The idea is investigated in three scenarios:
      1) oversampling in the full and reduced-rank EFSs; 2) a kernel learning technique
      maximizing the data class separation to study the influence of the feature space
      structure (implicitly defined by the kernel function); and 3) a unified framework
      for preferential oversampling that spans some of the previous approaches in the
      literature. We support our investigation with extensive experiments over 50
      imbalanced data sets.

PMID- 26316223
TI  - Feature Combination and the kNN Framework in Object Classification.
AB  - In object classification, feature combination can usually be used to combine the
      strength of multiple complementary features and produce better classification
      results than any single one. While multiple kernel learning (MKL) is a popular
      approach to feature combination in object classification, it does not always
      perform well in practical applications. On one hand, the optimization process in
      MKL usually involves a huge consumption of computation and memory space. On the
      other hand, in some cases, MKL is found to perform no better than the baseline
      combination methods. This observation motivates us to investigate the underlying
      mechanism of feature combination with average combination and weighted average
      combination. As a result, we empirically find that in average combination, it is
      better to use a sample of the most powerful features instead of all, whereas in
      one type of weighted average combination, the best classification accuracy comes
      from a nearly sparse combination. We integrate these observations into the k
      nearest neighbors (kNNs) framework, based on which we further discuss some issues
      related to sparse solution and MKL. Finally, by making use of the kNN framework,
      we present a new weighted average combination method, which is shown to perform
      better than MKL in both accuracy and efficiency in experiments. We believe that
      the work in this paper is helpful in exploring the mechanism underlying feature
      combination.

PMID- 26316224
TI  - Optimal Formation of Multirobot Systems Based on a Recurrent Neural Network.
AB  - The optimal formation problem of multirobot systems is solved by a recurrent
      neural network in this paper. The desired formation is described by the shape
      theory. This theory can generate a set of feasible formations that share the same
      relative relation among robots. An optimal formation means that finding one
      formation from the feasible formation set, which has the minimum distance to the
      initial formation of the multirobot system. Then, the formation problem is
      transformed into an optimization problem. In addition, the orientation, scale,
      and admissible range of the formation can also be considered as the constraints
      in the optimization problem. Furthermore, if all robots are identical, their
      positions in the system are exchangeable. Then, each robot does not necessarily
      move to one specific position in the formation. In this case, the optimal
      formation problem becomes a combinational optimization problem, whose optimal
      solution is very hard to obtain. Inspired by the penalty method, this
      combinational optimization problem can be approximately transformed into a convex
      optimization problem. Due to the involvement of the Euclidean norm in the
      distance, the objective function of these optimization problems are nonsmooth. To
      solve these nonsmooth optimization problems efficiently, a recurrent neural
      network approach is employed, owing to its parallel computation ability. Finally,
      some simulations and experiments are given to validate the effectiveness and
      efficiency of the proposed optimal formation approach. 

PMID- 26316225
TI  - Spatiochromatic Context Modeling for Color Saliency Analysis.
AB  - Visual saliency is one of the most noteworthy perceptual abilities of human
      vision. Recent progress in cognitive psychology suggests that: 1) visual saliency
      analysis is mainly completed by the bottom-up mechanism consisting of feedforward
      low-level processing in primary visual cortex (area V1) and 2) color interacts
      with spatial cues and is influenced by the neighborhood context, and thus it
      plays an important role in a visual saliency analysis. From a computational
      perspective, the most existing saliency modeling approaches exploit multiple
      independent visual cues, irrespective of their interactions (or are not computed
      explicitly), and ignore contextual influences induced by neighboring colors. In
      addition, the use of color is often underestimated in the visual saliency
      analysis. In this paper, we propose a simple yet effective color saliency model
      that considers color as the only visual cue and mimics the color processing in
      V1. Our approach uses region-/boundary-defined color features with
      spatiochromatic filtering by considering local color-orientation interactions,
      therefore captures homogeneous color elements, subtle textures within the object
      and the overall salient object from the color image. To account for color
      contextual influences, we present a divisive normalization method for chromatic
      stimuli through the pooling of contrary/complementary color units. We further
      define a color perceptual metric over the entire scene to produce saliency maps
      for color regions and color boundaries individually. These maps are finally
      globally integrated into a one single saliency map. The final saliency map is
      produced by Gaussian blurring for robustness. We evaluate the proposed method on
      both synthetic stimuli and several benchmark saliency data sets from the visual
      saliency analysis to salient object detection. The experimental results
      demonstrate that the use of color as a unique visual cue achieves competitive
      results on par with or better than 12 state-of-the-art approaches.

PMID- 26316226
TI  - Upper Respiratory Infections and MRI Activity in Relapsing-Remitting Multiple
      Sclerosis.
AB  - BACKGROUND: Although clinical reports have suggested a relationship between
      systemic infections and multiple sclerosis (MS) relapses, MRI evidence supporting
      an association is conflicting. Here we evaluated the temporal relationship
      between upper respiratory infections (URIs) and MRI activity in relapsing
      remitting (RR) MS. METHODS: We combined individual data on URI with data on
      active lesions in pre-scheduled MRI examinations performed every 4 weeks for 28
      weeks in 69 patients. A 4-week at-risk (AR) period started, by definition, 1 week
      before the onset of a URI. We recorded the relationship between the number of
      active lesions in each MRI with (1) the number of days of AR time in the
      immediately preceding 4-week period and (2) the number of days passed since the
      onset of a preceding URI. RESULTS: Average MRI lesions/day showed no difference
      between AR (0.0764) and not-AR (0.0774) periods. The number of lesions in 483 pre
      scheduled MRI examinations did not correlate with the AR proportion in the prior
      4-week period (rho = -0.03), and time from URI onset did not correlate with
      lesion number on the next MRI examination (rho = 0.003). CONCLUSION: The
      occurrence of a URI did not increase the risk of MRI activity evaluated in an
      adjacent 4-week window in RRMS.

PMID- 26316227
TI  - Nicotine Smoking Prevents the Effects of Frontotemporal Transcranial Direct
      Current Stimulation (tDCS) in Hallucinating Patients With Schizophrenia.

PMID- 26316228
TI  - Country Differences and Changes in Focus of Scientific Tobacco Control
      Publications between 2000 and 2012 in Europe.
AB  - BACKGROUND/AIMS: The Framework Convention on Tobacco Control (FCTC) stresses the
      importance of scientific research. We examined the differences between 31
      European countries regarding quantity and focus of tobacco control research
      publications. METHODS: PubMed, Web of Science, Scopus, and PsycInfo were searched
      for peer-reviewed articles on tobacco, written by European authors, published
      between 2000 and 2012. For 2000, 2004, 2008, and 2012 we further identified the
      main focus of the publication. RESULTS: The volume of European tobacco control
      scientific publications had almost doubled. Scandinavian countries had most
      publications per inhabitant, while Bulgaria, Cyprus, Estonia, Latvia, Lithuania,
      Malta, Romania, Slovakia, and Slovenia had relatively little research output.
      There was a smaller increase in publications about harm from tobacco, relative to
      publications about treatment, and education, and to publications about
      environmental interventions. In 2012, 49% of all publications were about health,
      while the total number of publications on environmental interventions was
      relatively small (10%). CONCLUSION: Research output had almost doubled, in line
      with global trends, but is still unevenly distributed across Europe. Although we
      observed a shift in European publications away from the harm of tobacco towards
      protecting smokers and changing the environment, the field is still dominated by
      publications on smoking and health.

PMID- 26316230
TI  - Looking at the heart of patients with chronic obstructive pulmonary disease.

PMID- 26316229
TI  - Postembryonic staging of wild-type goldfish, with brief reference to skeletal
      systems.
AB  - BACKGROUND: Artificial selection of postembryonic features is known to have
      established morphological variation in goldfish (Carassius auratus). Although
      previous studies have suggested that goldfish and zebrafish are almost directly
      comparable at the embryonic level, little is known at the postembryonic level.
      RESULTS: Here, we categorized the postembryonic developmental process in the wild
      type goldfish into 11 different stages. We also report certain differences
      between the postembryonic developmental processes of goldfish and zebrafish,
      especially in the skeletal systems (scales and median fin skeletons), suggesting
      that postembryonic development underwent evolutionary divergence in these two
      teleost species. CONCLUSIONS: Our postembryonic staging system of wild-type
      goldfish paves the way for careful and appropriate comparison with other teleost
      species. The staging system will also facilitate comparative ontogenic analyses
      between wild-type and mutant goldfish strains, allowing us to closely study the
      relationship between artificial selection and molecular developmental mechanisms
      in vertebrates.

PMID- 26316231
TI  - MDR-TB Antibody Response (Western Blot) to Fractions of Isoniazid and Rifampicin
      Resistant Antigens of Mycobacterium tuberculosis.
AB  - Drug-resistant TB poses a major threat to control of TB worldwide. Despite
      progress in the detection of Multidrug-resistant TB (MDR-TB) cases, a major
      diagnostic gap remains: 55% of reported TB patients estimated to have MDR-TB were
      not detected in 2013. MDR-TB antigens were conjugated to CNBr-activated Sepharose
      4B. Specific polyclonal antibodies against MDR-TB Ags were prepared in rabbits
      using two boosted injections of the MDR-TB antigen. The antibodies were purified
      and treated with susceptible TB to remove any non-specific and cross-reactive
      antibodies. In the present study, comparative analysis of electrophoretic pattern
      of different antigens of INH/RIF-resistant TB were studied for identifying
      protein profiles. A RIF-resistant TB antigen was shown here to have different
      protein profiles from INH-resistant TB isolate. The results of Western blotting
      analysis showed that in the RIF- and INH-resistant antigenic fractions some bands
      of 14.4 and 45 kDa as immunogenic were common. Moreover, four bands of RIF
      resistant TB antigen fractions (16, 19, 21, and 45 KDa) and one band of INH
      resistant TB (about 26 KDa) were detected as diagnostic antigens. This study
      suggests that the Western blot is an accurate test to survey INH- and RIF
      resistant TB antigens of M. tuberculosis infection. These findings indicate that
      MDR-TB diagnosis (based on Ag detection) could be useful in the identification of
      disease stages that precede symptomatic and microbiologically positive TB, such
      as subclinical and incipient TB.

PMID- 26316232
TI  - Effects of Phospholipase C on Fusarium graminearum Growth and Development.
AB  - Phospholipase C (PLC) plays important roles in regulating various biological
      processes in eukaryotes. Currently, little is known about the function of PLC in
      filamentous fungi, especially the plant pathogenic fungi. Fusarium graminearum is
      the causal agent of Fusarium head blight in many cereal crops. BLAST search
      revealed that Fusarium genome contains six FgPLC genes. Using quantitative RT
      PCR, different FgPLC gene expressions in mycelia were analyzed. To investigate
      the role of FgPLC in F. graminearum biology, a pharmacological study using a
      known inhibitor of PLC (U73122) was conducted. Results showed that inhibition of
      FgPLC resulted in significant alterations of mycelial growth, conidiation,
      conidial germination, perithecium formation, and expressions of Tri5 and Tri6
      genes. As expected, the treatment of F. graminearum with U73343, an inactive
      analog of U73122, showed no effect on F. graminearum biology. Our results
      suggested strongly that FgPLC plays important roles in F. graminearum growth and
      development. 

PMID- 26316234
TI  - Prognosis of Pain and Physical Functioning in Patients With Knee Osteoarthritis:
      A Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: To systematically summarize the literature on the course of pain in
      patients with knee osteoarthritis (OA), prognostic factors that predict
      deterioration of pain, the course of physical functioning, and prognostic factors
      that predict deterioration of physical functioning in persons with knee OA.
      METHODS: A search was conducted in PubMed, CINAHL, Embase, Psych-INFO, and
      SPORTDiscus up to January 2014. A meta-analysis and a qualitative data synthesis
      were performed. RESULTS: Of the 58 studies included, 39 were of high quality.
      High heterogeneity across studies (I(2)  >90%) and within study populations
      (reflected by large SDs of change scores) was found. Therefore, the course of
      pain and physical functioning was interpreted to be indistinct. We found strong
      evidence for a number of prognostic factors predicting deterioration in pain
      (e.g., higher knee pain at baseline, bilateral knee symptoms, and depressive
      symptoms). We also found strong evidence for a number of prognostic factors
      predicting deterioration in physical functioning (e.g., worsening in radiographic
      OA, worsening of knee pain, lower knee extension muscle strength, lower walking
      speed, and higher comorbidity count). CONCLUSION: Because of high heterogeneity
      across studies and within study populations, no conclusions can be drawn with
      regard to the course of pain and physical functioning. These findings support
      current research efforts to define subgroups or phenotypes within knee OA
      populations. Strong evidence was found for knee characteristics, clinical
      factors, and psychosocial factors as prognostics of deterioration of pain and
      physical functioning.

PMID- 26316235
TI  - A System for Real-Time Feedback to Improve Gait and Posture in Parkinson's
      Disease.
AB  - For people with Parkinson's disease (PD), gait and postural impairments can
      significantly affect their ability to perform activities of daily living.
      Presentation of appropriate cues has been shown to improve gait in PD. Based on
      this, a treadmill-based system and experimental paradigm were developed to
      determine if people with PD can utilize real-time feedback (RTFB) of step length
      or back angle (uprightness) to improve gait and posture. Eleven subjects (mean
      age 67 +/- 8 years) with mild-to-moderate PD (Hoehn and Yahr stage I-III) were
      evaluated regarding their ability to successfully utilize RTFB of back angle or
      step length during quiet standing and treadmill walking tasks during a single
      session in their medication-on state. Changes in back angle and step length due
      to feedback were compared using Friedman nonparametric tests with Wilcoxon Signed
      Rank tests for post-hoc comparisons. Improvements in uprightness were observed as
      an increase in back angle during quiet standing (p = 0.005) and during treadmill
      walking (p = 0.005) with back angle feedback when compared to corresponding tasks
      without feedback. Improvements in gait were also observed as an increase in step
      length (p = 0.005) during step length feedback compared to tasks without
      feedback. These results indicate that people with mild-to-moderate PD can utilize
      RTFB to improve upright posture and gait. Future work will investigate the long
      term effects of this RTFB paradigm and the development of systems for clinical or
      home-based use.

PMID- 26316236
TI  - Body-Sensor-Network-Based Kinematic Characterization and Comparative Outlook of
      UPDRS Scoring in Leg Agility, Sit-to-Stand, and Gait Tasks in Parkinson's
      Disease.
AB  - Recently, we have proposed a body-sensor-network-based approach, composed of a
      few body-worn wireless inertial nodes, for automatic assignment of Unified
      Parkinson's Disease Rating Scale (UPDRS) scores in the following tasks: Leg
      agility (LA), Sit-to-Stand (S2S), and Gait (G). Unlike our previous works and the
      majority of the published studies, where UPDRS tasks were the sole focus, in this
      paper, we carry out a comparative investigation of the LA, S2S, and G tasks. In
      particular, after providing an accurate description of the features identified
      for the kinematic characterization of the three tasks, we comment on the
      correlation between the most relevant kinematic parameters and the UPDRS scoring.
      We analyzed the performance achieved by the automatic UPDRS scoring system and
      compared the estimated UPDRS evaluation with the one performed by neurologists,
      showing that the proposed system compares favorably with typical interrater
      variability. We then investigated the correlations between the UPDRS scores
      assigned to the various tasks by both the neurologists and the automatic system.
      The results, based on a limited number of subjects with Parkinson's disease (PD)
      (34 patients, 47 clinical trials), show poor-to-moderate correlations between the
      UPDRS scores of different tasks, highlighting that the patients' motor
      performance may vary significantly from one task to another, since different
      tasks relate to different aspects of the disease. An aggregate UPDRS score is
      also considered as a concise parameter, which can provide additional information
      on the overall level of the motor impairments of a Parkinson's patient. Finally,
      we discuss a possible implementation of a practical e-health application for the
      remote monitoring of PD patients. 

PMID- 26316233
TI  - International Veterinary Epilepsy Task Force consensus proposal: medical
      treatment of canine epilepsy in Europe.
AB  - In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown
      considerably over the last years. Nevertheless, the same questions remain, which
      include, 1) when to start treatment, 2) which drug is best used initially, 3)
      which adjunctive AED can be advised if treatment with the initial drug is
      unsatisfactory, and 4) when treatment changes should be considered. In this
      consensus proposal, an overview is given on the aim of AED treatment, when to
      start long-term treatment in canine epilepsy and which veterinary AEDs are
      currently in use for dogs. The consensus proposal for drug treatment protocols,
      1) is based on current published evidence-based literature, 2) considers the
      current legal framework of the cascade regulation for the prescription of
      veterinary drugs in Europe, and 3) reflects the authors' experience. With this
      paper it is aimed to provide a consensus for the management of canine idiopathic
      epilepsy. Furthermore, for the management of structural epilepsy AEDs are
      inevitable in addition to treating the underlying cause, if possible. 

PMID- 26316237
TI  - Optic Disc Boundary and Vessel Origin Segmentation of Fundus Images.
AB  - This paper presents a novel classification-based optic disc (OD) segmentation
      algorithm that detects the OD boundary and the location of vessel origin (VO)
      pixel. First, the green plane of each fundus image is resized and morphologically
      reconstructed using a circular structuring element. Bright regions are then
      extracted from the morphologically reconstructed image that lie in close vicinity
      of the major blood vessels. Next, the bright regions are classified as bright
      probable OD regions and non-OD regions using six region-based features and a
      Gaussian mixture model classifier. The classified bright probable OD region with
      maximum Vessel-Sum and Solidity is detected as the best candidate region for the
      OD. Other bright probable OD regions within 1-disc diameter from the centroid of
      the best candidate OD region are then detected as remaining candidate regions for
      the OD. A convex hull containing all the candidate OD regions is then estimated,
      and a best-fit ellipse across the convex hull becomes the segmented OD boundary.
      Finally, the centroid of major blood vessels within the segmented OD boundary is
      detected as the VO pixel location. The proposed algorithm has low computation
      time complexity and it is robust to variations in image illumination, imaging
      angles, and retinal abnormalities. This algorithm achieves 98.8%-100% OD
      segmentation success and OD segmentation overlap score in the range of 72%-84% on
      images from the six public datasets of DRIVE, DIARETDB1, DIARETDB0, CHASE_DB1,
      MESSIDOR, and STARE in less than 2.14 s per image. Thus, the proposed algorithm
      can be used for automated detection of retinal pathologies, such as glaucoma,
      diabetic retinopathy, and maculopathy.

PMID- 26316238
TI  - Endocrinology of the Menopause.
AB  - In women, age-related changes in ovarian function begin in the mid-30s with
      decreased fertility and compensatory hormonal changes in the hypothalamus
      pituitary-gonadal axis that maintain follicle development and estrogen secretion
      in the face of a waning pool of ovarian follicles. The menopause transition is
      characterized by marked variability in follicle development, ovulation, bleeding
      patterns, and symptoms of hyper- and hypoestrogenism. The menopause, which is
      clinically defined by the last menstrual period, is followed by the consistent
      absence of ovarian secretion of estradiol. 

PMID- 26316240
TI  - Bone Health and Osteoporosis.
AB  - Osteoporosis is characterized by low bone mass and microarchitectural
      deterioration of bone tissue leading to decreased bone strength and an increased
      risk of low-energy fractures. Central dual-energy X-ray absorptiometry
      measurements are the gold standard for determining bone mineral density. Bone
      loss is an inevitable consequence of the decrease in estrogen levels during and
      following menopause, but additional risk factors for bone loss can also
      contribute to osteoporosis in older women. A well-balanced diet, exercise, and
      smoking cessation are key to maintaining bone health as women age. Pharmacologic
      agents should be recommended in patients at high risk for fracture. 

PMID- 26316239
TI  - Menopausal Symptoms and Their Management.
AB  - The menopause transition is associated with various symptoms, which can interact
      to produce morbidity. Vasomotor symptoms are the most commonly reported, but
      vaginal dryness/dyspareunia, sleep difficulties and adverse mood changes have all
      been shown to worsen as women approach menopause. For postmenopausal women
      changes in cognition are more likely to be related to aging and not to hormones.
      This article reviews the symptoms of hot flashes (vasomotor symptoms), vaginal
      dryness/dyspareunia, adverse mood, poor sleep/insomnia, and cognitive complaints,
      describing their epidemiology, diagnosis, and treatment. This article thus
      reviews the epidemiology, pathophysiology, diagnosis, and treatment of these
      common menopausal symptoms. 

PMID- 26316241
TI  - Surgical Menopause.
AB  - In addition to the common symptoms that occur after natural menopause, special
      considerations apply to women who have had their ovaries removed, particularly
      when oophorectomy occurs before age 45 years. Women with premenopausal
      oophorectomy have more severe and prolonged menopausal symptoms. Their risks of
      adverse mood, heart disease, excessive bone resorption, sexual dysfunction, and
      cognitive disorders are increased compared with the general population. Retention
      of the ovaries carries a survival benefit for women at low risk of ovarian
      malignancy. Women facing oophorectomy should understand the balance of risks and
      benefits in order to make an informed decision. 

PMID- 26316242
TI  - Premature Menopause.
AB  - A heterogeneous disorder, premature menopause is not an uncommon entity,
      affecting approximately 1% of women younger than 40 years. Multisystem
      implications are recognized as sequelae to the premature deprivation of ovarian
      steroids, posing unique health-related challenges in this population. An
      integrated management approach that addresses both the physical and psychological
      health concerns and the overall well-being of this relatively chronologically
      young population is paramount.

PMID- 26316243
TI  - Menopause and the Heart.
AB  - Cardiovascular disease is the leading cause of death in postmenopausal US women.
      The contribution of postmenopausal hormone replacement therapy to cardiovascular
      risk is one of the most controversial women's health topics. Strikingly
      discordant results, between observational and randomized clinical trials, have
      been reported. Remaining questions regarding time of hormone therapy initiation
      are discussed, as are ongoing trials focused on these questions. Cardiovascular
      concerns, cautions, and current recommendations for use are delineated. 

PMID- 26316244
TI  - Menopausal Hormone Therapy: Current Considerations.
AB  - Menopausal hormone therapy (MHT) is the most effective treatment for vasomotor
      and vaginal symptoms. Today, symptomatic women younger than 60 years of age or
      less than 10 years since onset of menopause yield the greatest benefit of MHT
      with the lowest risks when compared with older women remote from menopause.
      Careful assessment before initiating therapy includes severity of bothersome
      symptoms, treatment preferences, medical history, presence of contraindications
      to MHT, and personal risk of cardiovascular disease and breast cancer.
      Considerations of type of MHT, dosing, and route of administration, and
      recommendations regarding duration of therapy are discussed.

PMID- 26316246
TI  - Menopause and Cancers.
AB  - Cancer is a disease of aging, and therefore is more prevalent after menopause.
      Menopausal symptoms resulting from cancer treatments are an important
      survivorship issue in cancer care. This article reviews the preventive
      strategies, utilization of health resources, and management of menopausal
      symptoms after cancer treatment. Preventive screening as informed by genetic and
      lifestyle risk, and lifestyle modification, may mitigate the risk of cancer and
      cancer mortality. Despite potential benefits to quality of life, hormone
      replacement is rarely prescribed to survivors of gynecologic malignancies.
      Special considerations are needed for the treatment and supportive care of
      menopausal symptoms in cancer survivors. 

PMID- 26316245
TI  - The Effect of Menopausal Hormone Therapies on Breast Cancer: Avoiding the Risk.
AB  - Estrogen and P treatment results in greater risk of breast cancer than placebo.
      Treatment with estrogen alone does not increase the risk of breast cancer, may be
      used by women who have had a hysterectomy, and may even result in a decreased
      risk of breast cancer. Continued research seeks to improve the understanding of
      the interplay between estrogen and progestogens that predispose to adverse
      effects on breast tissue. Caution over this hypothesized benefit is warranted
      until it is substantiated by data on the incidence of breast cancer in tissue
      selective estrogen complex users. 

PMID- 26316247
TI  - Complementary and Alternative Approaches to Menopause.
AB  - Given the persistent confusion about the risks and benefits of hormone therapy
      since 2002 and the first publication from the Women's Health Initiative's primary
      findings, women and health care providers are increasingly motivated to find
      effective, nonhormonal approaches to treat menopause-related symptoms.
      Complementary and alternative medicine has grown increasingly popular in the last
      decade. A wide array of botanic medicines is offered as an alternative approach
      to hormone therapy for menopause, but data documenting efficacy and safety are
      limited. None of the available botanicals is as effective as hormone therapy in
      the management of vasomotor symptoms.

PMID- 26316248
TI  - Menopause and Sexuality.
AB  - Sexuality is an important component in the lives of menopausal women. Despite the
      importance of sexual function in menopausal women, sexual dysfunction increases
      with age. Age-related decline in sexual function may significantly reduce quality
      of life, making recognition of sexual dysfunction by physicians important for
      getting menopausal women effective care. Sexual dysfunction can result from
      multiple etiologies including psychosocial factors, medication side effects,
      vulvovaginal atrophy, chronic illness, or hypoactive sexual desire disorder.
      Discovering the etiology and identifying modifiable factors of the sexual
      function will help define appropriate treatment. 

PMID- 26316250
TI  - Postmenopausal Endocrinology. Foreword.

PMID- 26316249
TI  - Regulation of Body Composition and Bioenergetics by Estrogens.
AB  - Evidence points to an important role of estradiol (E2) in the regulation of body
      composition and bioenergetics. Basic and preclinical research shows that the
      disruption of E2 signaling through either genetic manipulation or surgical
      intervention accelerates fat accumulation, with a disproportionate increase in
      abdominal fat. Clinical evidence for the regulation of body composition and
      bioenergetics by E2 is less consistent. Evidence exists both for and against
      menopause as the mediator of changes in body composition. Thus, a need remains to
      better understand the metabolic actions of estrogens in women and the potential
      impact on health after the menopause. 

PMID- 26316251
TI  - Menopause and Perimenopause. Preface.

PMID- 26316252
TI  - Phonon properties of graphene derived from molecular dynamics simulations.
AB  - A method that utilises atomic trajectories and velocities from molecular dynamics
      simulations has been suitably adapted and employed for the implicit calculation
      of the phonon dispersion curves of graphene. Classical potentials widely used in
      the literature were employed. Their performance was assessed for each individual
      phonon branch and the overall phonon dispersion, using available inelastic x-ray
      scattering data. The method is promising for systems with large scale
      periodicity, accounts for anharmonic effects and non-bonding interactions with a
      general environment, and it is applicable under finite temperatures. The
      temperature dependence of the phonon dispersion curves has been examined with
      emphasis on the doubly degenerate Raman active Gamma-E2g phonon at the zone
      centre, where experimental results are available. The potentials used show
      diverse behaviour. The Tersoff-2010 potential exhibits the most systematic and
      physically sound behaviour in this regard, and gives a first-order temperature
      coefficient of chi = -0.05 cm(-1)/K for the Gamma-E2g shift in agreement with
      reported experimental values. 

PMID- 26316253
TI  - Gender differences in life expectancy with and without disability among older
      adults in Ecuador.
AB  - BACKGROUND: Knowledge on disability's impact among older women and men in Ecuador
      is limited. This paper provides gender-specific estimates of disability
      prevalence, life expectancy with and without disability, and the factors
      associated with gender differences in disability at older age in Ecuador (2009
      2010). METHODS: Data from the Health, Well-Being, and Aging Survey (SABE) Ecuador
      2009 was used. Participants were 4480 men and women aged 60 and over. Life
      expectancy with and without disability was calculated using the Sullivan method.
      Logistic regression analyses were used to explore gender differences in
      disability prevalence. Two disability measures, indicating limitations in
      activities of daily living (ADL) and instrumental activities of daily living
      (IADL), were used. RESULTS: 60-year-old women in Ecuador can expect to live 16.3
      years without ADL limitations compared to 16.9 years for men. Life expectancy
      without IADL limitations was 12.5 years for women and 15.5 years for men. At age
      60, women's length of life with ADL and IADL disability was higher (7.9 years for
      women vs. 4.9 years for men with ADL, and 11.7 years for women vs. 6.3 years for
      men with IADL). After controlling for socioeconomic characteristics, chronic
      conditions and lifestyle factors, gender differences in ADL disability were not
      statistically significant. However, older women were 58% more likely (OR=1.58,
      95% CI 1.27, 1.95) to report having IADL limitations than men, even after
      including control variables. CONCLUSION: Interventions should tackle chronic
      disease, physical inactivity, and socioeconomic differences to reduce women's
      vulnerability to disability in older age.

PMID- 26316254
TI  - Sensing of biomolecular interactions using fluorescence complementing systems in
      living cells.
AB  - Sensing biomolecule interactions in living cells allows for a deeper
      understanding of the mechanisms governing biological processes, and has
      increasing significance for improvements in clinical diagnosis. It is now
      possible by using molecular biosensors. One method involving molecular biosensors
      is called molecular fluorescence complementation, usually referred to as BiFC
      (bimolecular fragment/fluorescence complementary/complementation) or TriFC
      (trimolecular fragment complementary/complementation). This complementation
      method is based on the principle that two non-fluorescent fragments of a
      fluorescent protein are brought into sufficient lyclose proximity, upon which
      they are reconstructed so that fluorescence is re-established. This process
      relies on the interaction between the two fusion partners, which normally are
      proteins. This method is simple, noninvasive, sensitive, and does not require
      specialized tools, hence being available to most standard laboratories. Here, we
      selectively describe three relevant examples, although many other molecular
      interactions have been shown to work with this method. Recent developments of
      this method include multicolor BiFC, which allows for simultaneous detection of
      multi-biomolecule interactions, RNA-protein interactions, far red and near
      infrared sensing systems for deep tissue imaging. Challenges in the utilization
      of this method are discussed. Given the current rate of technological
      advancements, we believe that fluorescence fragment complementing systems have
      the potential to be utilized across a wide range of areas, including in routine
      research and clinical diagnosis. 

PMID- 26316255
TI  - Significant anthropogenic-induced changes of climate classes since 1950.
AB  - Anthropogenic forcings have contributed to global and regional warming in the
      last few decades and likely affected terrestrial precipitation. Here we examine
      changes in major Koppen climate classes from gridded observed data and their
      uncertainties due to internal climate variability using control simulations from
      Coupled Model Intercomparison Project 5 (CMIP5). About 5.7% of the global total
      land area has shifted toward warmer and drier climate types from 1950-2010, and
      significant changes include expansion of arid and high-latitude continental
      climate zones, shrinkage in polar and midlatitude continental climates, poleward
      shifts in temperate, continental and polar climates, and increasing average
      elevation of tropical and polar climates. Using CMIP5 multi-model averaged
      historical simulations forced by observed anthropogenic and natural, or natural
      only, forcing components, we find that these changes of climate types since 1950
      cannot be explained as natural variations but are driven by anthropogenic
      factors. 

PMID- 26316256
TI  - Alterations in the phosphoproteomic profile of cells expressing a non-functional
      form of the SHP2 phosphatase.
AB  - The phosphatase SHP-2 plays an essential role in growth factor signaling and
      mutations in its locus is the cause of congenital and acquired pathologies.
      Mutations of SHP-2 are known to affect the activation of the RAS pathway. Gain-of
      function mutations cause the Noonan syndrome, the most common non-chromosomal
      congenital disorder. In order to obtain a holistic picture of the intricate
      regulatory mechanisms underlying SHP-2 physiology and pathology, we set out to
      characterize perturbations of the cell phosphorylation profile caused by an
      altered localization of SHP-2. To describe the proteins whose activity may be
      directly or indirectly modulated by SHP-2 activity, we identified tyrosine
      peptides that are differentially phosphorylated in wild type SHP-2 cells and
      isogenic cells expressing a non-functional SHP-2 variant that cannot
      dephosphorylate the physiological substrates due to a defect in cellular
      localization upon growth factor stimulation. By an iTRAQ based strategy coupled
      to mass spectrometry, we have identified 63 phosphorylated tyrosine residues in
      53 different proteins whose phosphorylation is affected by SHP-2 activity. Some
      of these confirm already established regulatory mechanisms while many others
      suggest new possible signaling routes that may contribute to the modulation of
      the ERK and p38 pathways by SHP-2. Interestingly many new proteins that we found
      to be regulated by SHP-2 activity are implicated in the formation and regulation
      of focal adhesions. 

PMID- 26316257
TI  - Non-nasopharyngeal head and neck lymphoepithelioma-like carcinoma in the United
      States: A population-based study.
AB  - BACKGROUND: Non-nasopharyngeal head and neck lymphoepithelioma-like carcinoma
      (LELC) is a rate entity. The purpose of this study was to analyze its
      demographic, clinicopathologic, and survival characteristics. METHODS: A cohort
      from the Surveillance, Epidemiology, and End Results (SEER) database of cases
      with non-nasopharyngeal head and neck LELC between 1973 and 2011. RESULTS: There
      were 378 cases with 5-year overall survival (OS) of 70.5% and disease-specific
      survival (DSS) of 77.7%. The majority of cases were <60-year-old white men.
      Salivary gland LELC had the highest OS (80.8%) and DSS (85.7%) at 5 years.
      Multivariate analysis showed that older age, no surgery, and no radiation were
      independently significantly associated with worse survival (p < .05). CONCLUSION:
      Non-nasopharyngeal head and neck LELC is uncommon in the United States with
      salivary gland LELC having the highest OS and DSS compared with other head and
      neck sites. The optimal treatment with surgery and/or radiotherapy needs to be
      further investigated. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1294-E1300,
      2016.

PMID- 26316259
TI  - Positive relationship between p42.3 gene and inflammation in chronic non-atrophic
      gastritis.
AB  - OBJECTIVE: Gastric cancer (GC) is a typical type of inflammation-related tumor.
      The p42.3 gene is shown to be highly expressed in GC, but its association with
      gastritis remains unknown. We aimed to explore the relationship between gastric
      inflammation and p42.3 gene in vitro and in vivo. METHODS: Normal gastric
      epithelial cells (GES-1) were treated with Helicobacter pylori (H. pylori) and
      tumor necrosis factor (TNF)-alpha. Total cell mRNA and protein were extracted and
      collected, and polymerase chain reaction and Western blot were performed to
      determine the relative expression of p42.3 gene. In total, 291 biopsy samples
      from patients with chronic non-atrophic gastritis were collected and
      immunohistochemistry was used to measure the p42.3 protein expression. The
      association between p42.3 protein expression and the clinicopathological
      characteristics of these patients were analyzed. RESULTS: Both H. pylori and TNF
      alpha significantly enhanced the p42.3 protein expression in GES-1 cells in a
      time and dose-dependent manner. In addition, p42.3 gene expression was positively
      associated with the severity of gastric mucosal inflammation and H. pylori
      infection (P = 0.000). Its expression was significantly more common in severe
      gastric inflammation and in H. pylori-infected cases. CONCLUSION: p42.3 gene
      expression is associated with gastric mucosal inflammation that can be
      upregulated by TNF-alpha and H. pylori infection.

PMID- 26316260
TI  - Protocatechuic acid protects brain mitochondrial function in streptozotocin
      induced diabetic rats.
AB  - Brain mitochondrial dysfunction has been demonstrated in diabetic animals with
      neurodegeneration. Protocatechuic acid (PCA), a major metabolite of anthocyanin,
      has been shown to exert glycemic control and oxidative stress reduction in the
      heart. However, its effects on oxidative stress and mitochondrial function in the
      brain under diabetic condition have never been investigated. We found that PCA
      exerted glycemic control, attenuates brain mitochondrial dysfunction, and
      contributes to the prevention of brain oxidative stress in diabetic rats. 

PMID- 26316261
TI  - Chiroptical properties of streptorubin B: the synergy between theory and
      experiment.
AB  - Analysis of the calculated and measured optical rotation (OR) together with other
      calculated chiroptical properties such as electronic circular dichroism (ECD) and
      vibrational circular dichroism (VCD) of the prodigiosin alkaloid streptorubin B
      shows that these are dominated by the pseudoenantiomeric atropisomers anti-(S)
      streptorubin B (1A) and syn-(S)-streptorubin (1B). Atropisomerism is a dynamic
      phenomenon with a potentially nonequilibrium population of isomers, and
      accordingly the measured chiroptical responses may vary with time, concentration,
      temperature, and the anion of the salts used. Streptorubin also has the potential
      to form stacked homodimers for which the optical rotations measured at 589 nm can
      vary greatly due to the presence of ECD-active electronic transitions in this
      region.

PMID- 26316262
TI  - Brief Report: Cartilage Thickness Change as an Imaging Biomarker of Knee
      Osteoarthritis Progression: Data From the Foundation for the National Institutes
      of Health Osteoarthritis Biomarkers Consortium.
AB  - OBJECTIVE: To investigate the association of cartilage thickness change over 24
      months, as determined by magnetic resonance imaging (MRI), with knee
      osteoarthritis (OA) progression at 24-48 months. METHODS: This nested case
      control study included 600 knees with a baseline Kellgren/Lawrence (K/L) grade of
      1-3 from 600 Osteoarthritis Initiative (OAI) participants. Case knees (n = 194)
      had both medial tibiofemoral radiographic joint space loss (>=0.7 mm) and a
      persistent increase in the Western Ontario and McMaster Universities
      Osteoarthritis Index pain score (>=9 on a 0-100 scale) 24-48 months from
      baseline. Control knees (n = 406) included 200 with neither radiographic nor pain
      progression, 103 with radiographic progression only, and 103 with pain
      progression only. Medial and lateral femorotibial cartilage was segmented from
      sagittal 3T MRIs at baseline, 12 months, and 24 months. Logistic regression was
      used to assess the association of change in cartilage thickness, with a focus on
      the central medial femorotibial compartment, and OA progression. RESULTS: Central
      medial femorotibial compartment thickness loss was significantly associated with
      case status, with an odds ratio (OR) of 1.9 (95% confidence interval [95% CI] 1.6
      2.3) (P < 0.0001). Association with case status reached P < 0.05 for both the
      central femur (OR 1.8 [95% CI 1.5-2.2]) and the central tibia (OR 1.6 [95% CI 1.3
      1.9]). Lateral femorotibial compartment cartilage thickness loss, in contrast,
      was not significantly associated with case status. A reduction in central medial
      femorotibial compartment cartilage thickness was strongly associated with
      radiographic progression (OR 4.0 [95% CI 2.9-5.3]; P < 0.0001) and only weakly
      associated with pain progression (OR 1.3 [95% CI 1.1-1.6]; P < 0.01). CONCLUSION:
      Our findings indicate that loss of medial femorotibial cartilage thickness over
      24 months is associated with the combination of radiographic and pain progression
      in the knee, with a stronger association for radiographic progression.

PMID- 26316263
TI  - Population shuffling between ground and high energy excited states.
AB  - Stochastic processes powered by thermal energy lead to protein motions traversing
      time-scales from picoseconds to seconds. Fundamental to protein functionality is
      the utilization of these dynamics for tasks such as catalysis, folding, and
      allostery. A hierarchy of motion is hypothesized to connect and synergize fast
      and slow dynamics toward performing these essential activities. Population
      shuffling predicts a "top-down" temporal hierarchy, where slow time-scale
      conformational interconversion leads to a shuffling of the free energy landscape
      for fast time-scale events. Until now, population shuffling was only applied to
      interconverting ground states. Here, we extend the framework of population
      shuffling to be applicable for a system interconverting between low energy ground
      and high energy excited states, such as the SH3 domain mutants G48M and
      A39V/N53P/V55L from the Fyn tyrosine kinase, providing another tool for accessing
      the structural dynamics of high energy excited states. Our results indicate that
      the higher energy gauche - rotameric state for the leucine chi2 dihedral angle
      contributes significantly to the distribution of rotameric states in both the
      major and minor forms of the SH3 domain. These findings are corroborated with
      unrestrained molecular dynamics (MD) simulations on both the major and minor
      states of the SH3 domain demonstrating high correlations between experimental and
      back-calculated leucine chi2 rotameric populations. Taken together, we
      demonstrate how fast time-scale rotameric side-chain population distributions can
      be extracted from slow time-scale conformational exchange data further extending
      the scope and the applicability of the population shuffling model.

PMID- 26316264
TI  - Explore Transplant at Home: a randomized control trial of an educational
      intervention to increase transplant knowledge for Black and White
      socioeconomically disadvantaged dialysis patients.
AB  - BACKGROUND: Compared to others, dialysis patients who are socioeconomically
      disadvantaged or Black are less likely to receive education about deceased donor
      kidney transplant (DDKT) and living donor kidney transplant (LDKT) before they
      reach transplant centers, often due to limited availability of transplant
      education within dialysis centers. Since these patients are often less
      knowledgeable or ready to pursue transplant, educational content must be
      simplified, made culturally sensitive, and presented gradually across multiple
      sessions to increase learning and honor where they are in their decision-making
      about transplant. The Explore Transplant at Home (ETH) program was developed to
      help patients learn more about DDKT and LDKT at home, with and without telephone
      conversations with an educator. METHODS AND STUDY DESIGN: In this randomized
      controlled trial (RCT), 540 low-income Black and White dialysis patients with
      household incomes at or below 250 % of the federal poverty line, some of whom
      receive financial assistance from the Missouri Kidney Program, will be randomly
      assigned to one of three education conditions: (1) standard-of-care transplant
      education provided by the dialysis center, (2) patient-guided ETH (ETH-PG), and
      (3) health educator-guided ETH (ETH-EG). Patients in the standard-of-care
      condition will only receive education provided in their dialysis centers. Those
      in the two ETH conditions will receive four video and print modules delivered
      over an 8 month period by mail, with the option of receiving supplementary text
      messages weekly. In addition, patients in the ETH-EG condition will participate
      in multiple telephonic educational sessions with a health educator. Changes in
      transplant knowledge, decisional balance, self-efficacy, and informed decision
      making will be captured with surveys administered before and after the ETH
      education. DISCUSSION: At the conclusion of this RCT, we will have determined
      whether an education program administered to socioeconomically disadvantaged
      dialysis patients, over several months directly in their homes, can help more
      individuals learn about the options of DDKT and LDKT. We also will be able to
      examine the efficacy of different educational delivery approaches to further
      understand whether the addition of a telephone educator is necessary for
      increasing transplant knowledge. TRIAL REGISTRATION: ClinicalTrials.gov,
      NCT02268682.

PMID- 26316266
TI  - Public Attitudes Toward Sexual Expression in Long-Term Care: Does Context Matter?
AB  - The purpose of this study was to (a) examine how age and sex of long-term care
      (LTC) residents influence public attitudes toward sexuality in LTC and (b)
      understand how, in the absence of cognitive decline, residing in LTC influences
      the perception of sexuality as a basic human right. Attitudes were examined using
      a factorial vignette with a probability sample of 325 respondents from a southern
      state. Results indicate that attitudes were not statistically affected by a
      vignette character's age or sex; but respondent education level, parenthood
      status, and religious affiliation did have direct bearing on attitudes. The
      notion of sexuality as a basic human right for residents of LTC was ultimately
      challenged as 19% of respondents said that LTC residents should not be permitted
      to have sexual relations with their spouse in the facility.

PMID- 26316265
TI  - Homeostatic regulation of h-conductance controls intrinsic excitability and
      stabilizes the threshold for synaptic modification in CA1 neurons.
AB  - KEY POINTS: We determined the contribution of the hyperpolarization-activated
      cationic (h) current (Ih ) to the homeostatic regulation of CA1 pyramidal cells
      in vitro using chronic treatments (48 h) that either increase (picrotoxin) or
      decrease (kynurenate) neuronal activity. The h-conductance was found to be up- or
      down-regulated following chronic activity enhancement or activity deprivation,
      respectively. This bidirectional plasticity of Ih was found to subsequently alter
      both apparent input resistance and intrinsic neuronal excitability. Bidirectional
      homeostatic plasticity of Ih also determined EPSP waveform and EPSP summation
      tested at 5-30 Hz. Long-term synaptic modification induced by repetitive
      stimulation of the Schaffer collaterals was found to be constant across
      treatments in the presence of Ih but not when Ih was blocked pharmacologically.
      Thus, bidirectional homeostatic regulation of Ih stabilizes induction of long
      term synaptic modification in CA1 pyramidal neurons that depends on EPSP
      summation. ABSTRACT: The hyperpolarization-activated cationic (h) current is a
      voltage-shock absorber, highly expressed in the dendrites of CA1 pyramidal
      neurons. Up-regulation of Ih has been reported following episodes of intense
      network activity but the effect of activity deprivation on Ih and the functional
      consequence of homeostatic regulation of Ih remain unclear. We determined here
      the contribution of Ih to the homeostatic regulation of CA1 pyramidal cell
      excitability. Intrinsic neuronal excitability was decreased in neurons treated
      for 2-3 days with the GABAA channel blocker picrotoxin (PiTx) but increased in
      neurons treated (2-3 days) with the glutamate receptor antagonist kynurenate
      (Kyn). Membrane capacitance remained unchanged after treatment but the apparent
      input resistance was reduced for PiTx-treated neurons and enhanced for Kyn
      treated neurons. Maximal Ih conductance was up-regulated after chronic
      hyperactivity but down-regulated following chronic hypoactivity. Up-regulation of
      Ih in PiTx-treated cultures was found to accelerate EPSP kinetics and reduce
      temporal summation of EPSPs whereas opposite effects were observed in Kyn-treated
      cultures, indicating that homeostatic regulation of Ih may control the induction
      of synaptic modification depending on EPSP summation. In fact, stimulation of the
      Schaffer collaterals at 3-10 Hz induced differential levels of plasticity in PiTx
      treated and Kyn-treated neurons when Ih was blocked pharmacologically but not in
      control conditions. These data indicate that homeostatic regulation of Ih
      normalizes the threshold for long-term synaptic modification that depends on EPSP
      summation. In conclusion, bidirectional homeostatic regulation of Ih not only
      controls spiking activity but also stabilizes the threshold for long-term
      potentiation induced in CA1 pyramidal neurons by repetitive stimulation.

PMID- 26316267
TI  - Painful Choices: A Qualitative Exploration of Facilitators and Barriers to Active
      Lifestyles Among Adults With Osteoarthritis.
AB  - Research has indicated physical activity and exercise can effectively attenuate
      biopsychosocial osteoarthritis-related symptoms in adults, more so than other
      management strategies; however, both leisure and structured physical activity are
      scarcely recommended by health care providers, and remain rarely adopted and
      adhered to in this patient population. Using qualitative interviews, the present
      study investigated potential facilitators and barriers to physical activity for
      adults with osteoarthritis. Fifteen participants (30-85 years of age) with
      osteoarthritis engaged in semi-structured interviews, which focused on
      experiences with physical activity/exercise, daily osteoarthritis management, and
      experiences with health professionals' recommendations. Analysis of the interview
      transcripts revealed that pain relief, clear health-related communication, and
      social support facilitated physical activity. Physical pain, psychological
      distress, and inadequate medical support were the most frequently expressed
      barriers. The present study supports the biopsychosocial nature of
      osteoarthritis, which may have important implications for advancing exercise as
      an effective and long-term intervention strategy in aging adults with
      osteoarthritis.

PMID- 26316268
TI  - Middle-Aged and Older Adult Health Care Selection.
AB  - This study assesses the prevalence of primary-care physician (PCP) bypass among
      rural middle-aged and older adults. Bypass is a behavior where people travel
      beyond local providers to obtain health care. This article applies a precise
      Geographic Information System (GIS)-based measure of bypass and examines the role
      of community and non-health-care-related characteristics on bypass. Our results
      indicate that bypass behavior among rural middle-aged and older adults is
      multifaceted. In addition to the perceived quality of local primary care,
      dissatisfaction with local services, such as shopping, creates an effect that
      increases the likelihood of bypass, whereas strong community ties decrease the
      likelihood of bypass. The results suggest that the "outshopping theory," where
      respondents select services in larger regional economic centers rather than local
      "mom and pop" providers, now extends to older adult health care selection.

PMID- 26316269
TI  - Renal tubular acidosis with hyperchloremic acidosis: harmless with a sting?

PMID- 26316270
TI  - The toll of the gridiron: damage-associated molecular patterns and hypertension
      in American football.
AB  - American football has unequivocally been linked to elevations in blood pressure
      and hypertension, especially in linemen. However, the mechanisms of this increase
      cannot be attributed solely to increased body weight and associated
      cardiometabolic risk factors (e.g.,dyslipidemia or hyperglycemia). Therefore,
      understanding the etiology of football-associated hypertension is essential for
      improving the quality of life in this mostly young population, as well as for
      lowering the potential for chronic disease in the future. We propose that
      inflammatogenic damage-associated molecular patterns (DAMPs) released into the
      circulation from football-induced musculoskeletal trauma activate pattern
      recognition receptors of the innate immune system-specifically, high mobility
      group box 1 protein (HMGB1) and mitochondrial (mt)DNA which activate Toll-like
      receptor (TLR)4 and -9, respectively. Previously, we observed that circulating
      levels of these 2 DAMPs are increased in hypertension, and activation of TLR4 and
      -9 causes endothelial dysfunction and hypertension. Therefore, our novel
      hypothesis is that musculoskeletal injury from repeated hits in football players,
      particularly in linemen, leads to elevated circulating HMGB1 and mtDNA to
      activate TLRs on endothelial cells leading to impaired endothelium-dependent
      vasodilation, increased vascular tone, and hypertension.

PMID- 26316271
TI  - Transient receptor potential channel 1 maintains adherens junction plasticity by
      suppressing sphingosine kinase 1 expression to induce endothelial
      hyperpermeability.
AB  - Stability of endothelial cell (EC) adherens junctions (AJs) is central for
      prevention of tissue edema, the hallmark of chronic inflammatory diseases
      including acute respiratory distress syndrome. Here, we demonstrate a previously
      unsuspected role of sphingosine kinase 1 (SPHK1) in the mechanism by which
      transient receptor potential channel 1 (Trpc1)-mediated Ca(2+) entry destabilizes
      AJs. Trpc1(-/-) monolayers showed a 2.2-fold increase in vascular endothelial
      (VE)-cadherin cell-surface expression above wild-type (WT) monolayers. Thrombin
      increased endothelial permeability (evident by a 5-fold increase in
      interendothelial gap area and 60% decrease in transendothelial electrical
      resistance) in WT but not Trpc1(-/-) ECs. Trpc1(-/-) mice resisted the
      hyperpermeability effects of the edemagenic agonists used and exhibited 60% less
      endotoxin-induced mortality. Because sphingosine-1-phosphate (S1P) strengthens
      AJs, we determined if TRPC1 functioned by inhibiting SPHK1 activity, which
      generates S1P. Intriguingly, Trpc1(-/-) ECs or ECs transducing a TRPC1-inactive
      mutant showed a 1.5-fold increase in basal SPHK1 expression compared with WT ECs,
      resulting in a 2-fold higher S1P level. SPHK1 inhibitor SK1-I decreased basal
      transendothelial electrical resistance more in WT ECs (48 and 72% reduction at 20
      and 50 MUM, respectively) than in Trpc1(-/-) ECs. However, SK1-I pretreatment
      rescued thrombin-induced EC permeability in Trpc1(-/-) ECs. Thus, TRPC1
      suppression of basal SPHK1 activity enables EC-barrier destabilization by
      edemagenic agonists.

PMID- 26316272
TI  - Genotype, B-vitamin status, and androgens affect spaceflight-induced ophthalmic
      changes.
AB  - Ophthalmic changes have occurred in a subset of astronauts on International Space
      Station missions. Visual deterioration is considered the greatest human health
      risk of spaceflight. Affected astronauts exhibit higher concentrations of 1
      carbon metabolites (e.g., homocysteine) before flight. We hypothesized that
      genetic variations in 1-carbon metabolism genes contribute to susceptibility to
      ophthalmic changes in astronauts. We investigated 5 polymorphisms in the
      methionine synthase reductase (MTRR), methylenetetrahydrofolate reductase
      (MTHFR), serine hydroxymethyltransferase (SHMT), and cystathionine beta-synthase
      (CBS) genes and their association with ophthalmic changes after flight in 49
      astronauts. The number of G alleles of MTRR 66 and C alleles of SHMT1 1420 both
      contributed to the odds of visual disturbances. Preflight dehydroepiandrosterone
      was positively associated with cotton wool spots, and serum testosterone response
      during flight was associated with refractive change. Block regression showed that
      B-vitamin status and genetics were significant predictors of many of the
      ophthalmic outcomes that we observed. In one example, genetics trended toward
      improving (P = 0.10) and B-vitamin status significantly improved (P < 0.001) the
      predictive model for refractive change after flight. We document an association
      between MTRR 66 and SHMT1 1420 polymorphisms and spaceflight-induced vision
      changes. This line of research could lead to therapeutic options for both space
      travelers and terrestrial patients.

PMID- 26316273
TI  - A single serving of caffeinated coffee impairs postprandial glucose metabolism in
      overweight men.
AB  - Previous studies regarding the acute effects of coffee on glycaemic control have
      used a single large dose of coffee, typically containing the caffeine equivalent
      of 2-4 servings of coffee. This study investigates whether the acute effects of
      coffee are dose-dependent, starting with a single serving. A total of ten healthy
      overweight males participated in a two-part randomised double-blind cross-over
      study. In the first part, they ingested 2, 4 or 8 g instant decaffeinated coffee
      (DC) dissolved in 400 ml water with caffeine added in proportion to the DC (total
      100, 200 or 400 mg caffeine) or control (400 ml water) all with 50 g glucose. In
      the second part, they ingested the same amounts of DC (2, 4, 8 g) or control, but
      with a standard 100 mg caffeine added to each. Capillary blood samples were taken
      every 15 min for 2 h after each drink and glucose and insulin levels were
      measured. Repeated measures ANOVA on glucose results found an effect when
      caffeine was varied in line with DC (P=0.008). Post hoc analysis revealed that
      both 2 and 4 g DC with varied caffeine content increased the glycaemic response
      v. CONTROL: There was no effect of escalating doses of DC when caffeine remained
      constant at 100 mg. These results demonstrate that one standard serving of coffee
      (2 g) is sufficient to affect glucose metabolism. Furthermore, the amount of
      caffeine found in one serving (100 mg) is sufficient to mask any potential
      beneficial effects of increasing other components. No dose-dependent effect was
      found.

PMID- 26316275
TI  - Concurrent and Predictive Validity of Composite Methods to Assess Nutritional
      Status in Older Adults on Hemodialysis.
AB  - OBJECTIVE: To assess the performance of subjective global assessment (SGA),
      malnutrition inflammation score (MIS), and mini nutritional assessment short-form
      (MNA-SF) in older adults on hemodialysis (HD) by evaluating their concurrent and
      predictive validity. DESIGN: An observational and prospective study including
      older adults on HD. SETTING: Six dialysis units. SUBJECTS: We assessed 137 HD
      patients aged >=60 years (71.7% male, 70.2 +/- 7.2 years). MAIN OUTCOME MEASURES:
      The nutritional status was assessed by 7-point SGA, MIS and MNA-SF, and by
      objective methods. Patients were followed up for 14.5 (8; 26.3) months (median
      and interquartile) to assess survival. RESULTS: Protein energy wasting (PEW) was
      present in 63% of the patients when assessed by SGA, in 77% by MIS, and in 26% by
      MNA-SF. Most objective parameters of patients classified with PEW were lower (P <
      .05) than those from patients classified as well-nourished by SGA, MIS, and MNA
      SF. In addition, the hazard of death was higher for patients classified as PEW by
      SGA (hazard ratio 2.63 [95% confidence interval 1.14-6.00]), MIS (5.13 [1.19
      13.7]), and MNA-SF (2.53 [1.34-4.77]) in comparison to well-nourished patients.
      CONCLUSIONS: The prevalence of PEW varied depending on the tool applied. SGA,
      MIS, and MNA-SF had good concurrent and predictive validity for the assessment of
      nutritional status, but SGA and MIS were likely to perform better than MNA-SF.

PMID- 26316274
TI  - Comparison of bipolar hemiarthroplasty and total hip arthroplasty for displaced
      femoral neck fractures in the healthy elderly: a meta-analysis.
AB  - BACKGROUND: Displaced femoral neck fractures (FNFs) in healthy elderly patients
      have traditionally been managed with hemiarthroplasty (HA) or total hip
      arthroplasty (THA), with studies suggesting that THA may be the better option.
      However, it has recently been reported that bipolar HA (BHA) also provides good
      outcomes, and it is not clear as to whether BHA or THA is most appropriate. The
      purpose of this study was to conduct a meta-analysis of randomized controlled
      trials (RCTs) comparing the outcomes of BHA with THA for treating FNF in healthy
      elderly patients. METHODS: We searched the following databases from inception to
      May 2015 for relevant RCTs without language restrictions: PubMed, the Cochrane
      Central Register of Controlled Trials, Ovid MEDLINE and EMBASE, CINAHL, the China
      Biological Medicine Database, International Clinical Trials Registry Platform,
      Current Controlled Trials, and ClinicalTrials.gov. RCTs that met the inclusion
      criteria were statistically analyzed using the Cochrane review methods. RESULTS:
      Eight RCTs were included (total 1,014 patients; 523 had BHA and 491 had THA). The
      data from included RCTs were divided into four subgroups according to different
      follow-up durations. The Harris Hip Score after BHA was not different from that
      after THA in all subgroups. Both reoperation rate and acetabular erosion rate
      were higher after BHA after more than 4 years, while there was a higher
      dislocation rate associated with THA within 4 years. THA was more favorable
      regarding the EQindex-5D and the mobility and pain rate, while BHA was more
      favorable regarding operating time. No significant differences were found
      regarding infection rate, general complications, 1-year mortality, blood loss,
      and length of postoperative hospital stay. CONCLUSIONS: For healthy elderly
      patients with displaced FNFs, treatment with BHA led to better outcomes regarding
      dislocation rate, while THA was better regarding acetabular erosion rate and
      reoperation rate. When comparing BHA with THA, there were no significant
      differences in other important outcomes such as Harris Hip Score, infection rate,
      general complications, and 1-year mortality. Further high-quality RCTs are needed
      to provide robust evidence and evaluate the treatment options.

PMID- 26316276
TI  - Serum Phosphorus Levels, Race, and Socioeconomic Status in Incident Hemodialysis
      Patients.
AB  - OBJECTIVE: We sought to examine the relationship between race, socioeconomic
      status, and serum phosphorus levels in patients with end-stage renal disease
      incident to hemodialysis (HD) at a large, integrated health-care delivery system
      in Southern California. DESIGN: Retrospective cohort study. SUBJECTS: A total of
      5,778 adult patients who initiated HD at our institution between January 1, 2007
      and June 30, 2013. MAIN OUTCOME MEASURES: Unadjusted and adjusted time-averaged
      serum phosphorus levels and actual phosphorus levels over time. Phosphorus levels
      were also analyzed by repeated measures as a continuous measure and by phosphorus
      category. Baseline patient covariates included age, self-reported race, gender,
      cause of end-stage renal disease, and Charlson comorbidity index scores.
      Education and income level were estimated using geocoded data. RESULTS: A total
      of 68,372 phosphorus levels were available for 4,862 patients. Estimated annual
      family income fell below $40,001 in 66.1% of African Americans (AAs) and 62.7% of
      Hispanics compared with 43.5% of Asians and 43.7% of whites, P < .0001.
      Educational level fell into the highest category for whites (70.8%) compared with
      AA (44.8%) or Hispanic (30.5%) patients, P < .0001. Adjusted time-averaged
      phosphorus levels were lower among Hispanics (4.33 mg/dL, 95% confidence interval
      [CI] 4.27-4.40) compared with Asian (4.54 mg/dL, 95% CI 4.45-4.64, P < .001) and
      white patients (4.48 mg/dL, 95% CI 4.43-4.54, P < .001) but similar to AA
      patients. Asian patients experienced a significant increase in phosphorus levels
      over time (0.11 mg/dL per year, P < .0001). There were no significant effects of
      race, time, or race by time interactions in the unadjusted and adjusted
      categorical analyses of phosphorus levels. CONCLUSIONS: Our findings suggest that
      serum phosphorus levels are similar among HD patients, irrespective of race or
      socioeconomic status.

PMID- 26316277
TI  - Is the workplace a site of cardiac arrest like any other: Update from Paris Fire
      Brigade data.

PMID- 26316278
TI  - Are changes in cerebrovascular autoregulation following cardiac arrest associated
      with neurological outcome? Results of a pilot study.
AB  - PURPOSE: To investigate the association between impaired cerebrovascular
      autoregulation (CVAR) and outcome in comatose survivors of cardiac arrest.
      METHODS: The correlation in the time domain between cerebral tissue oxygenation
      (cStO2) using near infrared spectroscopy (NIRS) and mean arterial pressure was
      used to determine the tissue oxygenation index (TOx) as a reflection of normal
      (TOx<0) or impaired (TOx>0) CVAR. Daily measurements (>1h recording time) were
      performed in the first three days post cardiac arrest. Survival and neurological
      outcome was assessed at three months following cardiac arrest. A control group of
      healthy volunteers was also investigated. RESULTS: 23 patients and 28 volunteers
      were studied. All survivors (n=8) of cardiac arrest had a good neurological
      outcome. The TOx (median [interquartile range] for days 1-3) was higher (Mann
      Whitney test, p<0.001) in non-survivors (0.04 [-0.02 to -0.16]) compared to
      survivors (-0.11 [-0.19 to -0.02]) and healthy volunteers (-0.15 [-0.27 to 
      0.04]) on every day and for days 1-3 following cardiac arrest. The TOx was not
      significantly different between survivors and healthy volunteers. The cStO2 did
      not discriminate survivors (67 [62-72]%) from non-survivors (71 [65-75]%).
      Logistic regression analysis demonstrated TOx to be independently associated with
      survival at three months post cardiac arrest (odds ratio [95% confidence
      interval] 0.01 [0.01-0.50], p=0.04). CONCLUSIONS: Early impairment of CVAR
      following cardiac arrest is independently associated with mortality at three
      months follow-up. Assessments of CVAR could add to the management and
      prognostication during post-resuscitation care and should be further investigated
      as a guide to optimise cerebral perfusion pressure.

PMID- 26316279
TI  - Use of the learning conversation improves instructor confidence in life support
      training: An open randomised controlled cross-over trial comparing teaching
      feedback mechanisms.
AB  - AIMS: Feedback is vital for the effective delivery of skills-based education. We
      sought to compare the sandwich technique and learning conversation structured
      methods of feedback delivery in competency-based basic life support (BLS)
      training. METHODS: Open randomised crossover study undertaken between October
      2014 and March 2015 at the University of Birmingham, United Kingdom. Six-hundred
      and forty healthcare students undertaking a European Resuscitation Council (ERC)
      BLS course were enrolled, each of whom was randomised to receive teaching using
      either the sandwich technique or the learning conversation. Fifty-eight
      instructors were randomised to initially teach using either the learning
      conversation or sandwich technique, prior to crossing-over and teaching with the
      alternative technique after a pre-defined time period. Outcome measures included
      skill acquisition as measured by an end-of-course competency assessment,
      instructors' perception of teaching with each feedback technique and candidates'
      perception of the feedback they were provided with. RESULTS: Scores assigned to
      use of the learning conversation by instructors were significantly more
      favourable than for the sandwich technique across all but two assessed domains
      relating to instructor perception of the feedback technique, including all skills
      based domains. No difference was seen in either assessment pass rates (80.9%
      sandwich technique vs. 77.2% learning conversation; OR 1.2, 95% CI 0.85-1.84;
      p=0.29) or any domain relating to candidates' perception of their teaching
      technique. CONCLUSIONS & RELEVANCE: This is the first direct comparison of two
      feedback techniques in clinical medical education using both quantitative and
      qualitative methodology. The learning conversation is preferred by instructors
      providing competency-based life support training and is perceived to favour
      skills acquisition.

PMID- 26316280
TI  - Pathogenesis of bladder exstrophy: A new hypothesis.
AB  - Classical bladder exstrophy affects 1 in 30 000 live births. Results of surgical
      treatment from different institutions employing various surgical techniques are
      not uniform, thus there is a need for a consensus on the best technique for
      bladder exstrophy repair. Surgical correction in bladder exstrophy would be more
      effective if the exact pathogenetic mechanism was deduced and the procedure was
      directed to correct the cause, which is responsible for the defect. The anatomy
      of exstrophy shows that the infraumbilical abdominal wall, the anterior wall of
      the bladder, and the urethra are split, with splayed out genitalia and
      musculature along with pubic diastasis. There is no tissue loss and hence
      embryological defect is unlikely to be the cause of bladder exstrophy. Thus there
      is a need to examine pathogenesis of bladder exstrophy. METHODS: A literature
      search was made of the various hypotheses for cause of bladder exstrophy, and
      attempts were made to propose a new hypothesis. The present hypothesis is also
      the basis for a technique of mobilization of pelvic musculature, done in two
      stages. RESULTS: The functional outcomes of 38 children with bladder exstrophy
      managed over a period of 10 years were reviewed. At a mean follow-up of 4.5 years
      (range 2.5-8 years), 82% of patients were functionally continent. CONCLUSIONS:
      The exact embryopathogenesis of bladder exstrophy is unknown. In this study a new
      hypothesis is proposed, with the aim of tailoring the surgical procedure to
      correct this defect. Bladder exstrophy epispadias complex (BEEC) is a deformative
      disruption occurring after embryogenic phase and pubic diastasis, and is central
      to exstrophy development. A working hypothesis can be formulated in line with our
      observation so that future experiments based this new hypothesis can aim to
      elucidate the exact pathogenesis.

PMID- 26316281
TI  - Delocalized Surface State in Epitaxial Si(111) Film with Spontaneous ?3 * ?3
      Superstructure.
AB  - The "multilayer silicene" films were grown on Ag(111), with increasing thickness
      above 30 monolayers (ML). Scanning tunneling microscopy (STM) observations
      suggest that the "multilayer silicene" is indeed a bulk-like Si(111) film with a
      (?3 * ?3)R30 degrees  honeycomb superstructure on surface. The possibility for
      formation of Si(111)(?3 * ?3)R30 degrees -Ag reconstruction on the surface can be
      distinctively ruled out by peeling off the surface layer with the STM tip. On
      this surface, delocalized surface state as well as linear energy-momentum
      dispersion was observed from quasiparticle interference patterns. Our results
      indicate that a bulklike silicon film with diamondlike structure can also host
      delocalized surface state, which is even more attractive for potential
      applications, such as new generation of nanodevices based on Si. 

PMID- 26316283
TI  - Absolutely Exponential Stability and Temperature Control for Gas Chromatograph
      System Under Dwell Time Switching Techniques.
AB  - This paper provides a design strategy for temperature control of the gas
      chromatograph. Usually gas chromatograph is modeled by a simple first order
      system with a time-delay, and a proportion integration (PI) controller is widely
      used to regulate the output of the gas chromatograph to the desired temperature.
      As the characteristics of the gas chromatograph varies at the different
      temperature range, the single-model based PI controller cannot work well when
      output temperature varies from one range to another. Moreover, the presence of
      various disturbance will further deteriorate the performance. In order to improve
      the accuracy of the temperature control, multiple models are used at the
      different temperature ranges. With a PI controller designed for each model
      accordingly, a delay-dependent switching control scheme using the dwell time
      technique is proposed to ensure the absolute exponential stability of the closed
      loop. Experiment results demonstrate the effectiveness of the proposed switching
      technique.

PMID- 26316282
TI  - Differential expression of the chemosensory transcriptome in two populations of
      the stemborer Sesamia nonagrioides.
AB  - Among the proposed mechanisms of local adaptation to different ecological
      environments, transcriptional changes may play an important role. In this study,
      we investigated whether such variability occurred within the chemosensory organs
      of a herbivorous insect, for which chemosensation guides most of its host
      preferences. A European and an African population of the noctuid Sesamia
      nonagrioides that display significant differences in their ecological preferences
      were collected on Zea mays and Typha domingensis, respectively. RNAseq were used
      between the two populations for digital expression profiling of chemosensory
      organs from larval antennae and palps. Preliminary data on adult female antennae
      and ovipositors were also collected. We found 6,550 differentially expressed
      transcripts in larval antennae and palps. Gene ontology enrichment analyses
      suggested that transcriptional activity was overrepresented in the French
      population and that virus and defense activities were overrepresented in the
      Kenyan population. In addition, we found differential expression of a variety of
      cytochrome P450s, which may be linked to the different host-plant diets. Looking
      at olfactory genes, we observed differential expression of numerous candidate
      odorant-binding proteins, chemosensory proteins, and one olfactory receptor,
      suggesting that differences in olfactory sensitivity participate in insect
      adaptation. 

PMID- 26316284
TI  - Observer-Based Adaptive Backstepping Consensus Tracking Control for High-Order
      Nonlinear Semi-Strict-Feedback Multiagent Systems.
AB  - Combined with backstepping techniques, an observer-based adaptive consensus
      tracking control strategy is developed for a class of high-order nonlinear
      multiagent systems, of which each follower agent is modeled in a semi-strict
      feedback form. By constructing the neural network-based state observer for each
      follower, the proposed consensus control method solves the unmeasurable state
      problem of high-order nonlinear multiagent systems. The control algorithm can
      guarantee that all signals of the multiagent system are semi-globally uniformly
      ultimately bounded and all outputs can synchronously track a reference signal to
      a desired accuracy. A simulation example is carried out to further demonstrate
      the effectiveness of the proposed consensus control method.

PMID- 26316285
TI  - Distributed Optimization for a Class of Nonlinear Multiagent Systems With
      Disturbance Rejection.
AB  - The paper studies the distributed optimization problem for a class of nonlinear
      multiagent systems in the presence of external disturbances. To solve the
      problem, we need to achieve the optimal multiagent consensus based on local cost
      function information and neighboring information and meanwhile to reject local
      disturbance signals modeled by an exogenous system. With convex analysis and the
      internal model approach, we propose a distributed optimization controller for
      heterogeneous and nonlinear agents in the form of continuous-time minimum-phase
      systems with unity relative degree. We prove that the proposed design can solve
      the exact optimization problem with rejecting disturbances.

PMID- 26316286
TI  - Learning the Inverse Dynamics of Robotic Manipulators in Structured Reproducing
      Kernel Hilbert Space.
AB  - We investigate the modeling of inverse dynamics without prior kinematic
      information for holonomic rigid-body robots. Despite success in compensating
      robot dynamics and friction, general inverse dynamics models are nontrivial.
      Rigid-body models are restrictive or inefficient; learning-based models are
      generalizable yet require large training data. The structured kernels address the
      dilemma by embedding the robot dynamics in reproducing kernel Hilbert space. The
      proposed kernels autonomously converge to rigid-body models but require fewer
      samples; with a semi-parametric framework that incorporates additional parametric
      basis for friction, the structured kernels can efficiently model general rigid
      body robots. We tested the proposed scheme in simulations and experiments; the
      models that consider the structure of function space are more accurate.

PMID- 26316287
TI  - Highlighting Relationships of a Smartphone's Social Ecosystem in Potentially
      Large Investigations.
AB  - Social media networks are becoming increasingly popular because they can satisfy
      diverse needs of individuals (both personal and professional). Modern mobile
      devices are empowered with increased capabilities, taking advantage of the
      technological progress that makes them smarter than their predecessors. Thus, a
      smartphone user is not only the phone owner, but also an entity that may have
      different facets and roles in various social media networks. We believe that
      these roles can be aggregated in a single social ecosystem, which can be derived
      by the smartphone. In this paper, we present our concept of the social ecosystem
      in contemporary devices and we attempt to distinguish the different communities
      that occur from the integration of social networking in our lives. In addition,
      we propose techniques to highlight major actors within the ecosystem. Moreover,
      we demonstrate our suggested visualization scheme, which illustrates the linking
      of entities that live in separate communities using data taken from the
      smartphone. Finally, we extend our concept to include various parallel ecosystems
      during potentially large investigations and we link influential entities in a
      vertical fashion. We particularly examine cases where data aggregation is
      performed by specific applications, producing volumes of textual data that can be
      analyzed with text mining methods. Our analysis demonstrates the risks of the
      rising "bring your own device" trend in enterprise environments. 

PMID- 26316288
TI  - Stabilization for a Class of Switched Nonlinear Systems With Novel Average Dwell
      Time Switching by T-S Fuzzy Modeling.
AB  - In this paper, the problem of switching stabilization for a class of switched
      nonlinear systems is studied by using average dwell time (ADT) switching, where
      the subsystems are possibly all unstable. First, a new concept of ADT is given,
      which is different from the traditional definition of ADT. Based on the new
      proposed switching signals, a sufficient condition of stabilization for switched
      nonlinear systems with unstable subsystems is derived. Then, the T-S fuzzy
      modeling approach is applied to represent the underlying nonlinear system to make
      the obtained condition easily verified. A novel multiple quadratic Lyapunov
      function approach is also proposed, by which some conditions are provided in
      terms of a set of linear matrix inequalities to guarantee the derived T-S fuzzy
      system to be asymptotically stable. Finally, a numerical example is given to
      demonstrate the effectiveness of our developed results.

PMID- 26316289
TI  - Automatic 2.5-D Facial Landmarking and Emotion Annotation for Social Interaction
      Assistance.
AB  - People with low vision, Alzheimer's disease, and autism spectrum disorder
      experience difficulties in perceiving or interpreting facial expression of
      emotion in their social lives. Though automatic facial expression recognition
      (FER) methods on 2-D videos have been extensively investigated, their performance
      was constrained by challenges in head pose and lighting conditions. The shape
      information in 3-D facial data can reduce or even overcome these challenges.
      However, high expenses of 3-D cameras prevent their widespread use. Fortunately,
      2.5-D facial data from emerging portable RGB-D cameras provide a good balance for
      this dilemma. In this paper, we propose an automatic emotion annotation solution
      on 2.5-D facial data collected from RGB-D cameras. The solution consists of a
      facial landmarking method and a FER method. Specifically, we propose building a
      deformable partial face model and fit the model to a 2.5-D face for localizing
      facial landmarks automatically. In FER, a novel action unit (AU) space-based FER
      method has been proposed. Facial features are extracted using landmarks and
      further represented as coordinates in the AU space, which are classified into
      facial expressions. Evaluated on three publicly accessible facial databases,
      namely EURECOM, FRGC, and Bosphorus databases, the proposed facial landmarking
      and expression recognition methods have achieved satisfactory results. Possible
      real-world applications using our algorithms have also been discussed. 

PMID- 26316290
TI  - Low-Complexity Hand Gesture Recognition System for Continuous Streams of Digits
      and Letters.
AB  - In this paper, we propose a complete gesture recognition framework based on
      maximum cosine similarity and fast nearest neighbor (NN) techniques, which offers
      high-recognition accuracy and great computational advantages for three
      fundamental problems of gesture recognition: 1) isolated recognition; 2) gesture
      verification; and 3) gesture spotting on continuous data streams. To support our
      arguments, we provide a thorough evaluation on three large publicly available
      databases, examining various scenarios, such as noisy environments, limited
      number of training examples, and time delay in system's response. Our
      experimental results suggest that this simple NN-based approach is quite accurate
      for trajectory classification of digits and letters and could become a promising
      approach for implementations on low-power embedded systems. 

PMID- 26316291
TI  - Consensus of Multiagent Systems Using Aperiodic Sampled-Data Control.
AB  - This paper is concerned with the consensus of multiagent systems with nonlinear
      dynamics through the use of aperiodic sampled-data controllers, which are more
      flexible than classical periodic sampled-data controllers. By input delay
      approach, the resulting sampled-data system is reformulated as a continuous
      system with time-varying delay in the control input. A continuous Lyapunov
      functional, which captures the information on sampling pattern, together with the
      free-weighting matrix method, is then used to establish a sufficient condition
      for consensusability. For a more general case that the sampled-data controllers
      are subject to constant input delays, a novel discontinuous Lyapunov functional
      is introduced on the basis of the vector extension of Wirtinger's inequality.
      This functional can lead to simplified and efficient stability conditions for
      computation and optimization. Further results on the estimate of maximal
      allowable sampling interval upper bound is given as well. Numerical example is
      provided to show the effectiveness and merits of the proposed protocol. 

PMID- 26316293
TI  - Facial reanimation using hypoglossal-facial neurorrhaphy with end-to-side
      coaptation between the jump interpositional nerve graft and hypoglossal nerve:
      Outcome and duration of preoperative paralysis.
AB  - BACKGROUND: In this report, we described the use of hypoglossal-facial
      neurorrhaphy with end-to-side coaptation between the jump interpositional nerve
      graft and the hypoglossal nerve for facial reanimation and analyzed the
      relationship between the outcome of surgery and duration of preoperative
      paralysis. METHODS: We performed hypoglossal-facial neurorrhaphy with the jump
      interpositional nerve graft on nine men and 10 women with unilateral complete
      facial paralysis. The patients, with a mean age of 39.7 +/- 18.1 years (range, 8
      65 years) at the time of surgery, experienced preoperative paralysis ranging from
      1 to 150 months (mean, 16.9 +/- 34.9 months). The movement of the corners of the
      mouth was evaluated 12 months after surgery using a unique method based on the
      House-Brackmann grading scale. RESULTS: The mean follow-up was 5.6 +/- 1.6 years
      (range, 3-9 years). The movement of the corners of mouth was classified as
      excellent in two cases, good in seven cases, fair in two cases, and poor in eight
      cases. Nine of the 11 cases with preoperative paralysis of 6 months or less had
      excellent or good results, whereas none of the eight cases with preoperative
      paralysis of 7 months or longer yielded excellent or good results, showing a
      significant difference (P = 0.01). CONCLUSIONS: To achieve successful reanimation
      of the corners of the mouth, hypoglossal-facial neurorrhaphy with end-to-side
      coaptation between the jump interpositional nerve graft and the hypoglossal nerve
      should be performed within 6 months after the onset of facial nerve paralysis.
      (c) 2015 Wiley Periodicals, Inc. Microsurgery 36:460-466, 2016.

PMID- 26316292
TI  - Spontaneous Reconstitution of Functional Transmembrane Proteins During
      Bioorthogonal Phospholipid Membrane Synthesis.
AB  - Transmembrane proteins are critical for signaling, transport, and metabolism, yet
      their reconstitution in synthetic membranes is often challenging. Non-enzymatic
      and chemoselective methods to generate phospholipid membranes in situ would be
      powerful tools for the incorporation of membrane proteins. Herein, the
      spontaneous reconstitution of functional integral membrane proteins during the de
      novo synthesis of biomimetic phospholipid bilayers is described. The approach
      takes advantage of bioorthogonal coupling reactions to generate proteoliposomes
      from micelle-solubilized proteins. This method was successfully used to
      reconstitute three different transmembrane proteins into synthetic membranes.
      This is the first example of the use of non-enzymatic chemical synthesis of
      phospholipids to prepare proteoliposomes.

PMID- 26316295
TI  - FOXM1 is overexpressed in B-acute lymphoblastic leukemia (B-ALL) and its
      inhibition sensitizes B-ALL cells to chemotherapeutic drugs.
AB  - The Forkhead box protein M1 (FOXM1) is a transcription factor that plays a
      central role in the regulation of cell cycle, proliferation, DNA repair, and
      apoptosis. FOXM1 is overexpressed in many human tumors and its upregulation has
      been linked to high proliferation rates and poor prognosis. We therefore studied
      the role of FOXM1 in B-lymphoblastic leukemia (B-ALL) in order to understand
      whether FOXM1 could be a key target for leukemia therapy. RT-PCR and western blot
      analysis were carried out in a small cohort of pediatric B-ALL patients to
      evaluate FOXM1 levels. To assess its biological relevance, its expression was
      down-modulated by transient RNA interference in B-ALL cell lines (REH and NALM
      6). Our results show that FOXM1 expression is higher in both B-ALL patients and
      cell lines when compared to PBMC or normal B-cells (CD19+) from healthy donors.
      Furthermore, blocking FOXM1 activity in two B-ALL cell lines, by either knockdown
      or treatment with the FOXM1 inhibitor thiostrepton, causes significant decrease
      in their cell proliferation. This decrease in cell proliferation was coupled with
      both an induction of the G2/M cell cycle arrest and with a reduction in the S
      phase population. Finally, we noted how thiostrepton synergises with
      chemotherapeutic agents commonly used in B-ALL therapy, thus increasing their
      efficiency. Therefore our results suggest that FOXM1 is highly expressed in both
      patients and B-ALL cell lines, and that targeting FOXM1 could be an attractive
      strategy for leukemia therapy and for overcoming drug resistance.

PMID- 26316296
TI  - Past and future evolution of Abies alba forests in Europe - comparison of a
      dynamic vegetation model with palaeo data and observations.
AB  - Information on how species distributions and ecosystem services are impacted by
      anthropogenic climate change is important for adaptation planning. Palaeo data
      suggest that Abies alba formed forests under significantly warmer-than-present
      conditions in Europe and might be a native substitute for widespread drought
      sensitive temperate and boreal tree species such as beech (Fagus sylvatica) and
      spruce (Picea abies) under future global warming conditions. Here, we combine
      pollen and macrofossil data, modern observations, and results from transient
      simulations with the LPX-Bern dynamic global vegetation model to assess past and
      future distributions of A. alba in Europe. LPX-Bern is forced with climate
      anomalies from a run over the past 21 000 years with the Community Earth System
      Model, modern climatology, and with 21st-century multimodel ensemble results for
      the high-emission RCP8.5 and the stringent mitigation RCP2.6 pathway. The
      simulated distribution for present climate encompasses the modern range of A.
      alba, with the model exceeding the present distribution in north-western and
      southern Europe. Mid-Holocene pollen data and model results agree for southern
      Europe, suggesting that at present, human impacts suppress the distribution in
      southern Europe. Pollen and model results both show range expansion starting
      during the Bolling-Allerod warm period, interrupted by the Younger Dryas cold,
      and resuming during the Holocene. The distribution of A. alba expands to the
      north-east in all future scenarios, whereas the potential (currently unrealized)
      range would be substantially reduced in southern Europe under RCP8.5. A. alba
      maintains its current range in central Europe despite competition by other
      thermophilous tree species. Our combined palaeoecological and model evidence
      suggest that A. alba may ensure important ecosystem services including stand and
      slope stability, infrastructure protection, and carbon sequestration under
      significantly warmer-than-present conditions in central Europe.

PMID- 26316294
TI  - Optimizing Antibiotic Stewardship in Nursing Homes: A Narrative Review and
      Recommendations for Improvement.
AB  - The emerging crisis in antibiotic resistance and concern that we now sit on the
      precipice of a post-antibiotic era have given rise to advocacy at the highest
      levels for widespread adoption of programmes that promote judicious use of
      antibiotics. These antibiotic stewardship programmes, which seek to optimize
      antibiotic choice when clinically indicated and discourage antibiotic use when
      clinically unnecessary, are being implemented in an increasing number of acute
      care facilities, but their adoption has been slower in nursing homes. The
      antibiotic prescribing process in nursing homes is fundamentally different from
      that observed in hospital and clinic settings, with formidable challenges to
      implementation of effective antibiotic stewardship. Nevertheless, an emerging
      body of research points towards ways to improve antibiotic prescribing practices
      in nursing homes. This review summarizes the findings of this research and
      presents ways in which antibiotic stewardship can be implemented and optimized in
      the nursing home setting. 

PMID- 26316297
TI  - Erratum to: Is entheses ultrasound reliable? A reading Latin American exercise.

PMID- 26316299
TI  - In reference to "A novel configuration of a traditional rapid response team
      decreases non-intensive care unit arrests and overall hospital mortality".

PMID- 26316298
TI  - Gastric bypass alters both glucose-dependent and glucose-independent regulation
      of islet hormone secretion.
AB  - OBJECTIVE: Roux-en-Y gastric bypass surgery (GB) is characterized by accentuated
      but short-lived postprandial elevations of blood glucose and insulin. This
      profile has been attributed to effects of relative hyperglycemia to directly
      stimulate beta-cells and an augmented incretin effect. An additional glucose
      independent stimulation of insulin secretion in GB subjects was hypothesized.
      METHODS: Fifteen subjects with prior GB, six matched obese non surgical controls,
      and seven lean individuals were recruited. Islet hormones were measured before
      and after meal ingestion during hyperinsulinemic hypoglycemic clamps to minimize
      the direct effects of glycemia and glucose-dependent gastrointestinal hormones on
      insulin secretion. RESULTS: The GB subjects had less suppression of fasting beta
      cell secretion during the insulin clamp compared to controls. In addition, meal
      induced insulin secretion increased in the GB subjects but not controls during
      fixed sub-basal glycemia. In contrast, the glucagon responses to hypoglycemia and
      meal ingestion were lower in the GB subjects than controls. CONCLUSIONS: Among
      subjects with GB, the response of insulin and glucagon secretion to decreasing
      blood glucose is blunted, but meal-induced insulin secretion is stimulated even
      at fixed systemic sub-basal glycemia. These findings indicate that, following GB,
      islet hormone secretion is altered as a result of factors beyond circulatory
      glucose levels.

PMID- 26316300
TI  - Laparoscopic repair of congenital midureteric strictures in infants and children.
AB  - PURPOSE: Congenital midureteric strictures (CMUS) are an uncommon cause of
      obstructive uropathy. There are only a few case reports of laparoscopic
      management of CMUS. We present our experience with laparoscopic repair of CMUS in
      7 children. PATIENTS AND METHODS: The records of all children (n=7, 5 infants)
      undergoing laparoscopic reconstruction for CMUS were reviewed. Preoperative
      imaging included ultrasound (US) and diuretic renography (DR) in all children.
      Intravenous urography or magnetic resonance urography was performed in 3 children
      when a dilated ureter was seen on the ultrasound. Retrograde pyelography was
      performed in 6 children before definitive surgery. All children underwent
      transperitoneal laparoscopic excision of the stricture with ureteroureterostomy.
      Follow-up included clinical examination and US in all children, with DR in 5
      children. RESULTS: Over a 3-year period, 7 children underwent laparoscopic repair
      of CMUS. Six children had antenatally diagnosed hydronephrosis, while one child
      presented with infected hydronephrosis, underwent nephrostomy and was later
      referred to us. The diagnosis of CMUS was suspected preoperatively in 4 children;
      in 3 children, diagnosis of CMUS was confirmed on retrograde pyelography.
      Laparoscopic repair was successfully completed in all children; there were no
      significant intraoperative or postoperative complications. At a median follow-up
      of 18months, all children are asymptomatic, with US (7) and DR (5) confirming
      significant reduction in the hydronephrosis and improved drainage. The cosmetic
      results have been excellent. CONCLUSION: To our knowledge, this is the first
      report of laparoscopic repair of CMUS in children. Laparoscopic repair of CMUS
      can be safely and successfully performed even in small infants, with good
      results.

PMID- 26316301
TI  - Reversed autogenous sternal plate flaps for treatment of sternal clefts: A novel
      technique.
AB  - OBJECTIVE: A sternal cleft is an extremely rare congenital anomaly resulting from
      a failure of the fusion of the sternal bars. The condition can be classified as
      complete or incomplete, where there is an inferior or less commonly a superior
      attachment. We report our experience with a modified surgical technique using a
      reverse autogenous sternal plate flap to treat complete sternal clefts in
      children beyond the neonatal period without the need for any prosthetic material
      or disruption of the chest wall structure. PATIENTS AND METHODS: The technique
      was performed on three patients beyond the neonatal period at the age of 2, 4 and
      12years. Two patients were female and one was a male. All cases were performed by
      a single surgeon. Parents were consented for the new technique. Institutional
      review board (IRB) approval was obtained. RESULTS: Recovery in all children was
      uncomplicated, and they were discharged home after 4, 4 and 5days respectively.
      There were no morbidities among all 3 patients. Review at 4 and 12weeks revealed
      complete wound healing and a well-united sternum. All remain asymptomatic on a
      median follow-up period of 22months. CONCLUSIONS: Our new technique in repairing
      complete sternal clefts was easy, reproducible and generated satisfactory results
      on a reasonable follow up period. Most importantly we avoided the use of
      prosthetic material and any disruption to the chest wall structure in a subgroup
      of older patients.

PMID- 26316302
TI  - A Romanian version of the UCLA Scleroderma Clinical Trial Consortium
      Gastrointestinal Tract Instrument.
AB  - OBJECTIVES: UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract
      (UCLA SCTC GIT 2.0) Instrument is a comprehensive, self-administered survey for
      the assessment of gastrointestinal involvement in scleroderma patients, developed
      and validated in English. Our objective was to translate and validate a Romanian
      version of UCLA SCTC GIT 2.0. METHODS: Translation from English into Romanian has
      been made using the forward-backward method. Sixty-four patients, attending a
      referral centre as part of an extensively studied cohort, were approached in a
      consecutive manner over a period of two years for administration of the
      questionnaire. We evaluated the reproducibility, internal consistency, construct
      validity and discriminative capacity of the translation (Romanian GIT). RESULTS:
      Fifty-four patients returned completed questionnaires. Internal consistency was
      demonstrated by Cronbach's alpha coefficient (0.931). Construct validity is
      supported by moderate, but significant correlations of Romanian GIT total score
      with the Mental Component Summary (MCS) of SF-36 (r=0.541, Spearman correlation)
      and among subscales, by significant correlations with SHAQ total score (r=0.559,
      Spearman correlation) and by strong correlations with gastrointestinal subscale
      of SHAQ (SHAQ GI) (r=0.726, Spearman correlation). Reproducibility was good as
      well. Divergent validity was supported by significant differences between
      patients with or without a clinical diagnosis of gastrointestinal disease. Other
      differences in the Romanian GIT total score were tested among subgroups of
      patients. CONCLUSIONS: The Romanian GIT has acceptable reliability and validity.
      This questionnaire can be used for the assessment of gastrointestinal involvement
      in scleroderma patients.

PMID- 26316304
TI  - Victim Reports of Bystander Reactions to In-Person and Online Peer Harassment: A
      National Survey of Adolescents.
AB  - Bullying prevention is increasingly targeting education to bystanders, but more
      information is needed on the complexities of bystander actions across a wide
      variety of incidents, including both online and in-person peer harassment. The
      current study analyzes victim report data from a nationally representative survey
      of youth ages 10-20 (n = 791; 51% female). Bystander presence was common across
      all harassment incident types (80% of incidents). In contrast to previous
      research, our study found that supportive bystander behaviors occurred at
      relatively high rates. Unfortunately, antagonistic bystander behaviors, although
      less common, were predictive of higher negative impact for the victim. A large
      percentage of victims (76%) also disclosed the harassment to confidants, who play
      an important role as secondary bystanders. While friends were the most common
      confidant, incidents were also disclosed to adults at high rates (60%) and with
      mostly positive results. The findings suggest that prevention programs could
      increase their impact by targeting education to both direct witnesses and
      confidants, and considering a wider variety of peer victimization incident types.

PMID- 26316303
TI  - Cardiomyocytes induce macrophage receptor shedding to suppress phagocytosis.
AB  - BACKGROUND: Mobilization of the innate immune response to clear and metabolize
      necrotic and apoptotic cardiomyocytes is a prerequisite to heart repair after
      cardiac injury. Suboptimal kinetics of dying myocyte clearance leads to secondary
      necrosis, and in the case of the heart, increased potential for collateral loss
      of neighboring non-regenerative myocytes. Despite the importance of myocyte
      phagocytic clearance during heart repair, surprisingly little is known about its
      underlying cell and molecular biology. OBJECTIVE: To determine if phagocytic
      receptor MERTK is expressed in human hearts and to elucidate key sequential steps
      and phagocytosis efficiency of dying adult cardiomyocytes, by macrophages.
      RESULTS: In infarcted human hearts, expression profiles of the phagocytic
      receptor MER-tyrosine kinase (MERTK) mimicked that found in experimental ischemic
      mouse hearts. Electron micrographs of myocardium identified MERTK signal along
      macrophage phagocytic cups and Mertk-/- macrophages contained reduced digested
      myocyte debris after myocardial infarction. Ex vivo co-culture of primary
      macrophages and adult cardiomyocyte apoptotic bodies revealed reduced engulfment
      relative to resident cardiac fibroblasts. Inefficient clearance was not due to
      the larger size of myocyte apoptotic bodies, nor were other key steps preceding
      the formation of phagocytic synapses significantly affected; this included
      macrophage chemotaxis and direct binding of phagocytes to myocytes. Instead,
      suppressed phagocytosis was directly associated with myocyte-induced inactivation
      of MERTK, which was partially rescued by genetic deletion of a MERTK proteolytic
      susceptibility site. CONCLUSION: Utilizing an ex vivo co-cultivation approach to
      model key cellular and molecular events found in vivo during infarction,
      cardiomyocyte phagocytosis was found to be inefficient, in part due to myocyte
      induced shedding of macrophage MERTK. These findings warrant future studies to
      identify other cofactors of macrophage-cardiomyocyte cross-talk that contribute
      to cardiac pathophysiology.

PMID- 26316306
TI  - Thermal luminescence quenching of amine-functionalized silicon quantum dots: a pH
      and wavelength-dependent study.
AB  - Understanding and resolving the mechanisms that affect the photoluminescence (PL)
      of Si QDs are of great importance because of their strong potential for
      optoelectronic and solar cell materials. In this article, the intrinsic exciton
      dynamics of water-dispersed allylamine-functionalized silicon quantum dots (Si
      QDs) have been explored as a function of temperature by means of steady-state and
      time-resolved PL spectroscopy. Significant PL quenching of Si QDs has been
      observed with increase in temperature from 278 K to 348 K. This thermal quenching
      is found to be a reversible process. The mechanism involves nonradiative
      reversible relaxation of conduction band electrons through the thermally-created
      temporary trap states. These temporary trap states arise due to the displacement
      of surface atoms from their regular positions at elevated temperature. Upon
      cooling, these surface irregularities relax back to their equilibrium positions
      with retrieval of the original PL intensity. It has been observed that the
      quenching mechanism is strongly influenced by the pH and excitation wavelength
      (lambdaex). At pH 3.5, the quenching mechanism involves nonradiative relaxation
      of conduction band electrons through the thermally-created temporary trap states.
      However, at pH 7.4, the unprotonated surface amine groups introduce permanent
      nitrogen-related surface defects inside the bandgap of Si QDs. At elevated
      temperature, the conduction band electrons get trapped in these nitrogen-related
      surface defects through the involvement of thermally-created temporary trap
      states. Subsequent exciton recombination of these nitrogen-related defect states
      results in red-shifted green color luminescence. By using the Arrhenius equation
      we have estimated the activation energy of this nonradiative thermal relaxation
      process and it was found to be 138 and 139 meV at pH 3.5 and pH 7.4,
      respectively. 

PMID- 26316305
TI  - Nice Guys and Gals Finish Last? Not in Early Adolescence When Empathic, Accepted,
      and Popular Peers are Desirable.
AB  - Little is known about attributes that elicit romantic desirability in early
      adolescence. The current study, with a sample of 531 sixth-grade students (45%
      boys) attending ethnically diverse middle schools, used a resource control
      framework to explore which self-reported behaviors (e.g., empathy and aggression)
      and peer-reported status (e.g., acceptance and perceived popularity) predict the
      likelihood of being considered romantically desirable (i.e., receiving at least
      one "crush" nomination from an opposite sex grademate). Self-reported empathy was
      positively associated with students' romantic desirability (primarily for those
      with high peer acceptance), whereas self-reported aggression on its own did not.
      Both peer-acceptance and popularity also were positively associated with
      students' romantic desirability, and aggressive behavior reduced popularity's
      effect. Although aggression may be integral for obtaining high peer status across
      cultures, prosocial behaviors were romantically valued. Our findings suggest that
      peer-vetted social status elicits romantic interest and during early adolescence,
      nice guys and gals really do not finish last.

PMID- 26316308
TI  - Endoscopic resection of a giant esophageal lipoma: a case report.

PMID- 26316307
TI  - Therapeutic Monoclonal Antibodies: What Headache Specialists Need to Know.
AB  - BACKGROUND: Monoclonal antibodies (mAbs) are now an important part of the
      treatment armamentarium for a wide range of conditions including cancer,
      autoimmune diseases, inflammatory diseases of the joint and bowel, transplant
      rejection, and multiple sclerosis. Significant progress over the last 30 years in
      the development of therapeutic mAbs has resulted in improved efficacy and safety.
      Monoclonal antibodies approved for the treatment of neurological illnesses so far
      are limited to use in multiple sclerosis. Several therapeutic mAbs have completed
      phase 2 clinical trials for migraine prevention, and there are phase 3 trials
      underway for migraine prophylaxis and for cluster headache at the time of this
      writing. AIM: The purpose of this review is to discuss the characteristics of
      mAbs, including their mechanism of action and safety profile, and briefly
      describe the mAbs being evaluated for the prevention of migraine and cluster
      headaches. SUMMARY: Monoclonal antibodies have several features that distinguish
      them from small molecules, including very high selectivity, relatively long half
      life that generally allows for once or twice monthly dosing, and significantly
      reduced potential for drug-drug interactions or other nontarget related
      toxicities. The clinical development of mAbs that target calcitonin gene-related
      peptide and its receptor is underway and will evaluate this promising new drug
      class for the prevention of migraine and cluster headache.

PMID- 26316309
TI  - Highly compressible and all-solid-state supercapacitors based on nanostructured
      composite sponge.
AB  - Based on polyaniline-single-walled carbon nanotubes -sponge electrodes, highly
      compressible all-solid-state supercapacitors are prepared with an integrated
      configuration using a poly(vinyl alcohol) (PVA)/H2 SO4 gel as the electrolyte.
      The unique configuration enables the resultant supercapacitors to be compressed
      as an integrated unit arbitrarily during 60% compressible strain. Furthermore,
      the performance of the resultant supercapacitors is nearly unchanged even under
      60% compressible strain. 

PMID- 26316310
TI  - The linkage between infant negative temperament and parenting self-efficacy: the
      role of resilience against negative performance feedback.
AB  - Caring for infants with negative reactive temperament may tax parents' confidence
      in their caregiving ability, or parenting self-efficacy (PSE). This may happen in
      particular in parents who interpret these signals as negative feedback on their
      performance. To test this hypothesis, 179 first-time pregnant women were
      presented a caregiving simulation that provided positive and negative feedback on
      their attempts to comfort a crying baby. According to their PSE resilience to
      negative feedback during the task, they were grouped in a high resilient and low
      resilient group. PSE was followed up at 32 weeks of pregnancy and 3 and 12 months
      after birth, while perceived temperament of the child was assessed at 3 and 12
      months after birth. Results showed that among women with low resilience against
      negative feedback, perceived negative temperament was negatively associated with
      PSE at 3 months, whereas no such association was observed among women with high
      resilience against negative feedback. Implications of the concept of resilience
      for the study of PSE are discussed. 

PMID- 26316311
TI  - Three-dimensional architecture of tandem repeats in chicken interphase nucleus.
AB  - Tandem repeats belong to a class of genomic repetitive elements that form arrays
      of head-to-tail monomers. Due to technical difficulties in sequencing and
      assembly of large tandem repeat arrays, it remains largely unknown by which
      mechanisms tandem-repeat-containing regions aid in maintenance of ordered radial
      genome organization during interphase. Here we analyzed spatial distribution of
      several types of tandem repeats in interphase nuclei of chicken MDCC-MSB1 cells
      and somatic tissues relative to heterochromatin compartments and nuclear center.
      We showed that telomere and subtelomere repeats generally localize at the nuclear
      or chromocenters periphery. A tandem repeat known as CNM, typical for centromere
      regions of gene-dense microchromosomes, forms interchromosome clusters and
      occupies DAPI-positive chromocenters that appear predominantly within the nuclear
      interior. In contrast, centromere-specific tandem repeats of the majority of gene
      poor macrochromosomes are embedded into the peripheral layer of heterochromatin.
      Chicken chromocenters rarely comprise centromere sequences of both macro- and
      microchromosomes, whose territories localize in different radial nuclear zones.
      Possible mechanisms of observed tandem repeats positioning and its implication in
      highly ordered arrangement of chromosome territories in chicken interphase
      nucleus are discussed. 

PMID- 26316312
TI  - Scaffold-Hopping of Multicationic Amphiphiles Yields Three New Classes of
      Antimicrobials.
AB  - Quaternary ammonium compounds (QACs) are a vital class of antiseptics. Recent
      investigations into their construction are uncovering novel and potent
      multicationic variants. Based on a trisQAC precedent, we have implemented a
      scaffold-hopping approach to develop alternative QAC architectures that display 1
      3 long alkyl chains in specific projections from cyclic and branched core
      structures bearing 3-4 nitrogen atoms. The preparation of 30 QAC structures
      allowed for correlation of scaffold structure with antimicrobial activity. We
      identified QACs with limited conformational flexibility that have improved
      bioactivity against planktonic bacteria as compared to their linear counterparts.
      We also confirmed that resistance, as evidenced by an increased minimum
      inhibitory concentration (MIC) for methicillin-resistant Staphylococcus aureus
      (MRSA) compared to methicillin-susceptible Staphylococcus aureus (MSSA), can
      reduce efficacy up to 64-fold for monocationic QACs. Differentiation of
      antimicrobial and anti-biofilm activity, however, was not observed, suggesting
      that these compounds utilize a non-specific mode of eradication. 

PMID- 26316313
TI  - Consolidation of proteomics data in the Cancer Proteomics database.
AB  - Cancer is a class of diseases characterized by abnormal cell growth and one of
      the major reasons for human deaths. Proteins are involved in the molecular
      mechanisms leading to cancer, furthermore they are affected by anti-cancer drugs,
      and protein biomarkers can be used to diagnose certain cancer types. Therefore,
      it is important to explore the proteomics background of cancer. In this report,
      we developed the Cancer Proteomics database to re-interrogate published proteome
      studies investigating cancer. The database is divided in three sections related
      to cancer processes, cancer types, and anti-cancer drugs. Currently, the Cancer
      Proteomics database contains 9778 entries of 4118 proteins extracted from 143
      scientific articles covering all three sections: cell death (cancer process),
      prostate cancer (cancer type) and platinum-based anti-cancer drugs including
      carboplatin, cisplatin, and oxaliplatin (anti-cancer drugs). The detailed
      information extracted from the literature includes basic information about the
      articles (e.g., PubMed ID, authors, journal name, publication year), information
      about the samples (type, study/reference, prognosis factor), and the proteomics
      workflow (Subcellular fractionation, protein, and peptide separation, mass
      spectrometry, quantification). Useful annotations such as hyperlinks to UniProt
      and PubMed were included. In addition, many filtering options were established as
      well as export functions. The database is freely available at
      http://cancerproteomics.uio.no. 

PMID- 26316314
TI  - Photoreduction of CO2 on TiO 2/SrTiO 3 Heterojunction Network Film.
AB  - Nanotube titanic acid (NTA) network film has a porous structure and large BET
      surface area, which lead them to possessing high utilization of the incident
      light and strong adsorption ability. We used NTA as the precursor to fabricate a
      TiO2/ SrTiO3 heterojunction film by the hydrothermal method. In the process of
      the reaction, part of NTA reacted with SrCl2 to form SrTiO3 nanocubes, and the
      remainder dehydrated to transform to the rutile TiO2. The ratio of TiO2 and
      SrTiO3 varied with the hydrothermal reaction time. SEM and TEM images indicated
      that SrTiO3 nanocubes dispersed uniformly on TiO2 film, and the particle size and
      crystallinity of SrTiO3 nanocubes increased with the reaction time prolonging.
      The TiO2/SrTiO3 heterojunction obtained by 1 h showed the best activity for CO2
      photoreduction, where the mole ratio of TiO2 and SrTiO3 was 4:1. And the photo
      conversion efficiency of CO2 to CH4 improved remarkably after the foreign
      electron traps of Pt and Pd nanoparticles were loaded. The highest photocatalytic
      production rate of CH4 reached 20.83 ppm/h cm(2). In addition, the selectivity of
      photoreduction product of CO2 was also increased apparently when Pd acted as the
      cocatalyst on TiO2/SrTiO3 heterojunction film. 

PMID- 26316315
TI  - Palladium-Catalyzed Oxidative Cycloisomerization of 2-Cinnamyl-1,3-Dicarbonyls:
      Synthesis of Functionalized 2-Benzyl Furans.
AB  - A new palladium-catalyzed intramolecular oxidative cycloisomerization of readily
      available starting materials, 2-cinnamyl-1,3-dicarbonyls, has been demonstrated
      for the creation of structurally diverse 2-benzyl furans. The cycloisomerization
      occurs by a regioselective 5-exo-trig pathway. The reaction shows a broad
      substrate scope with good to excellent yields. Furthermore, a one-pot procedure
      has been executed by using readily available cinnamyl alcohols and 1,3-diketones.

PMID- 26316316
TI  - Prevalence and management of oropharyngeal dysphagia in patients with severe
      anorexia nervosa: A large retrospective review.
AB  - OBJECTIVE: Oropharyngeal dysphagia (OPD) refers to difficulty swallowing food or
      a liquid bolus from the oral and pharyngeal cavities into the esophagus and
      increases the risk of possibly life-threatening pneumonia. Little has been
      reported on OPD in adults with anorexia nervosa (AN). This study includes a
      description of OPD in severe AN and discusses potentially effective clinical
      management. METHOD: Two hundred and six adults with severe AN, admitted over a
      five-year period to a national referral center specializing in the
      multidisciplinary medical stabilization of this population, were retrospectively
      evaluated by electronic database query and manual chart review. All patients
      whose initial medical assessment triggered a speech-language pathology (SLP)
      consultation, due to concerns for OPD, were reviewed in detail. RESULTS: Of the
      206 total patients, 42 presented with symptoms of OPD and received SLP
      consultation. In the OPD cohort, 37 (88%) were women, with median age 32 years
      old, and mean admission weights of 57% ideal body weight (IBW) and body mass
      index (BMI) of 12 kg/m(2). Compared with those who did not have OPD, OPD patients
      had significantly lower BMI on admission (12 kg/m(2) vs. 13.1 kg/m(2), p <
      0.001), longer stay (21 days vs. 14 days, p < 0.001), and were more medically
      compromised, including a greater incidence of refeeding hypophosphatemia (60.9%
      vs. 29.7%, p < 0.004). DISCUSSION: Clinical awareness of OPD may reduce the
      incidence of aspiration pneumonia and promote life-saving oral nutrition in
      patients with severe AN. Proper, timely evaluation and intervention may improve
      clinical outcomes.

PMID- 26316317
TI  - Interleukin-6 expression by interactions between gynecologic cancer cells and
      human mesenchymal stem cells promotes epithelial-mesenchymal transition.
AB  - Epithelial-to-mesenchymal transition (EMT) facilitates the invasion and
      metastasis of cancer cells. EMT seems to be mediated by the interaction between
      cancer cells and human mesenchymal stem cells (hMSCs) in the tumor
      microenvironment. The present study is intended to identify specific cytokines as
      potent inducers of EMT associated hMSCs-tumor interactions. We used ovarian
      cancer cell lines (SKOV-3 and IGROV-1), endometrial cancer cell line (Ishikawa)
      and hMSCs (bone marrow MSC, amniotic membrane MSC and decidua MSC). The
      expressions of EMT markers (E-cadherin, Snail, Twist and N-cadherin) were
      analyzed using quantitative RT-PCR, immunofluorescence and western blot analysis.
      Matrix metalloproteinases (MMP-2 and MMP-9), Matrigel invasion assay, and wound
      healing assay were used to analyze cell migration and invasion. Gynecologic
      cancer cells directly co-cultured with hMSCs had contact-dependent altered
      morphology and growth patterns. IL-6 was elevated in all co-cultures using a
      human cytokine array. After IL-6 treatment of cancer cell lines, RT-PCR and
      western blot analysis indicated a decrease in an epithelial marker and an
      increase in mesenchymal markers. Also, cancer cells with IL-6 significantly
      increase in MMP-2 and MMP-9 and significantly enhance the migration ability
      compared to untreated cells (P<0.05), as shown by wound healing assay. On
      Matrigel invasion assay, treated cells displayed significantly increased
      invasiveness compared to untreated cancer cells. Gyneocologic cancer cells
      exposed to IL-6 acquired mesenchymal properties that facilitated metastasis and
      invasion by promoting EMT. The present study suggests that IL-6 of the tumor
      microenvironment has a critical role in oncogenic EMT. 

PMID- 26316318
TI  - Obesity in children with different risk factors for obstructive sleep apnea: a
      community-based study.
AB  - This study investigated the association between obesity and obstructive sleep
      apnea (OSA) in preschool and school-age children. Parents of obese and randomly
      chosen normal weight children completed a questionnaire on sleep-related
      symptoms, demography, family, and medical history. All subjects were invited to
      undergo polysomnography (PSG). OSA cases were defined as obstructive apnea
      hypopnea index (OAHI) >=1. A total of 5930 children were studied with 9.5% obese
      (11.9% boys/6.1% girls), 205/2680 preschool and 360/3250 school children. There
      were 1030 children (535 obese/495 normal weight) who underwent PSG. OSA was
      higher in obese children and obese school children had higher OAHI, arousal
      index, and shorter total sleep time. However, there was no positive correlation
      between OSA and body mass index (BMI). The main risk factors for OSA in preschool
      children were adenotonsillar hypertrophy and recurrent respiratory tract
      infection. The main cause for OSA in school children was a history of parental
      snoring and obesity. Mallampati scores and sleep-related symptoms were found to
      be associated with OSA in both preschool and school children. CONCLUSION: We
      demonstrated differential risk factors for OSA in obese children, which suggest
      that a different mechanism may be involved in OSA development in preschool and
      school-age children. WHAT IS KNOWN: Various risk factors have been reported in
      obese children with OSA owing to the different age and different study design.
      Obese children have a higher prevalence and severity of obstructive sleep apnea
      (OSA). OSA risk factors in obese children are affected by different ages and
      study designs. WHAT IS NEW: A differential prevalence and risk factors for obese
      preschool and school-age children with OSA has been demonstrated.

PMID- 26316319
TI  - Large Study But Weak Test of Internal Validation: Comment on the Article by
      Solomon et al.

PMID- 26316320
TI  - Somatic mutations associated with leukemic progression of familial platelet
      disorder with predisposition to acute myeloid leukemia.

PMID- 26316322
TI  - Metal-free aerobic one-pot synthesis of substituted/annulated quinolines from
      alcohols via indirect Friedlander annulation.
AB  - Metal-free, operationally simple, and highly efficient one-pot aerobic process
      for the synthesis of functionalized/annulated quinolines is devised from easily
      available 2-aminobenzyl alcohol/2-aminobenzophenones and alkyl/aryl alcohols for
      the first time. The process involves two sequential reactions, namely in situ
      aerial oxidation of alcohols to the corresponding aldehydes/ketones followed by
      Friedlander annulation. 

PMID- 26316321
TI  - Hybrid Mesoporous Silica-Based Drug Carrier Nanostructures with Improved
      Degradability by Hydroxyapatite.
AB  - Potential bioaccumulation is one of the biggest limitations for silica nanodrug
      delivery systems in cancer therapy. In this study, a mesoporous silica
      nanoparticles/hydroxyapatite (MSNs/HAP) hybrid drug carrier, which enhanced the
      biodegradability of silica, was developed by a one-step method. The morphology
      and structure of the nanoparticles were characterized by TEM, DLS, FT-IR, XRD, N2
      adsorption-desorption isotherms, and XPS, and the drug loading and release
      behaviors were tested. TEM and ICP-OES results indicate that the degradability of
      the nanoparticles has been significantly improved by Ca(2+) escape from the
      skeleton in an acid environment. The MSNs/HAP sample exhibits a higher drug
      loading content of about 5 times that of MSNs. The biological experiment results
      show that the MSNs/HAP not only exhibits good biocompatibility and antitumor
      effect but also greatly reduces the side effects of free DOX. The as-synthesized
      hybrid nanoparticles may act as a promising drug delivery system due to their
      good biocompatibility, high drug loading efficiency, pH sensitivity, and
      excellent biodegradability. 

PMID- 26316323
TI  - Olfactory Neuroblastoma: A Case Report.
AB  - A 43-year-old female presented with persistent nasal congestion with intermittent
      epistaxis without resolution for the preceding 5 years. Clinical examination
      revealed a large pink rubbery mass, medial to the middle turbinate in the right
      nasal cavity extending to the choana. Radiographic images demonstrated a
      heterogeneously enhancing lobular soft tissue mass filling the right nasal
      cavity, causing lateral bowing of the right medial orbital wall and extending
      posteriorly to the right anterior ethmoid sinus. The clinical, radiographic,
      histologic, and immunohistochemical features of olfactory neuroblastoma are
      discussed.

PMID- 26316324
TI  - Cryptic insertion of 3'FOXO1 into inverted chromosome arm 2q in the presence of
      two normal chromosome 13s and 13 small interstitial duplications in a patient
      with alveolar rhabdomyosarcoma.
AB  - Alveolar rhabdomyosarcoma (ARMS) is a pediatric soft tissue neoplasm with a
      characteristic translocation, t(2;13)(q35;q14), which is detected in 70-80% of
      cases. This well-described translocation produces the gene fusion product PAX3
      FOXO1. Cryptic rearrangements of this fusion have never before been reported in
      ARMS. Here we describe a patient with ARMS that showed, by fluorescence in situ
      hybridization and G-banded chromosomes, a cryptic insertion of 3'FOXO1 into
      inverted chromosome 2q. The inversion breakpoints were depicted by array
      comparative genomic hybridization as two small interstitial duplications, one of
      which involved the PAX3 gene. In addition, the array comparative genomic
      hybridization results revealed 1q gain, 16q loss, and 11 more small duplications,
      with one of them involving the FOXO1 gene. Although the pathogenesis in classic
      ARMS cases is thought to be driven by the 5'PAX3-3'FOXO1 fusion on derivative
      chromosome 13, here we report a novel cryptic insertion of 3'FOXO1 resulting in a
      pathogenic fusion with 5'PAX3 on inverted chromosome 2q. 

PMID- 26316325
TI  - Long-Term Safety and Efficacy of Epratuzumab in the Treatment of Moderate-to-
      Severe Systemic Lupus Erythematosus: Results From an Open-Label Extension Study.
AB  - OBJECTIVE: The primary objective was to assess the long-term safety of repeated
      courses of epratuzumab therapy in patients with moderate-to-severe systemic lupus
      erythematosus. Secondary objectives were to assess long-term efficacy and health
      related quality of life (HRQOL). METHODS: Eligible patients from the 12-week,
      phase IIb, randomized, placebo-controlled EMBLEM study enrolled into the open
      label extension (OLE) study, SL0008. In the SL0008 study, patients received 1,200
      mg epratuzumab infusions at weeks 0 and 2 of repeating 12-week cycles, plus
      standard of care. Safety measures included treatment-emergent adverse events
      (TEAEs) and serious TEAEs. Efficacy measures included combined treatment
      response, the British Isles Lupus Assessment Group score, the Systemic Lupus
      Erythematosus Disease Activity Index score, and the physician's and patient's
      global assessment of disease activity. Total daily corticosteroid dose and HRQOL
      (by the Short Form 36 health survey) were also assessed. RESULTS: A total of 113
      of the 203 patients (55.7%) who entered the SL0008 study continued epratuzumab
      therapy until study closure (total cumulative exposure: 381.3 patient-years,
      median exposure: 845 days, and maximum exposure: 1,185 days/approximately 3.2
      years). TEAEs were reported in 192 patients (94.6%); most common were infections
      and infestations (68.0%, 138 patients). Serious TEAEs were reported in 51
      patients (25.1%), and 14 patients (6.9%) had serious infections. In patients
      treated for 108 weeks (n = 116), the median corticosteroid dose was reduced from
      10.0 mg/day at OLE screening to 5.0 mg/day at week 108. Improvements in efficacy
      and HRQOL measures in EMBLEM were maintained in the OLE, while placebo patients
      exhibited similar improvements in disease activity upon a switch to epratuzumab.
      CONCLUSION: Open-label epratuzumab treatment was well tolerated for up to 3.2
      years, and associated with sustained improvements in disease activity and HRQOL,
      while steroids were reduced.

PMID- 26316326
TI  - Hidden Genetic Variation in LCA9-Associated Congenital Blindness Explained by
      5'UTR Mutations and Copy-Number Variations of NMNAT1.
AB  - Leber congenital amaurosis (LCA) is a severe autosomal-recessive retinal
      dystrophy leading to congenital blindness. A recently identified LCA gene is
      NMNAT1, located in the LCA9 locus. Although most mutations in blindness genes are
      coding variations, there is accumulating evidence for hidden noncoding defects or
      structural variations (SVs). The starting point of this study was an LCA9
      associated consanguineous family in which no coding mutations were found in the
      LCA9 region. Exploring the untranslated regions of NMNAT1 revealed a novel
      homozygous 5'UTR variant, c.-70A>T. Moreover, an adjacent 5'UTR variant, c.
      69C>T, was identified in a second consanguineous family displaying a similar
      phenotype. Both 5'UTR variants resulted in decreased NMNAT1 mRNA abundance in
      patients' lymphocytes, and caused decreased luciferase activity in human retinal
      pigment epithelial RPE-1 cells. Second, we unraveled pseudohomozygosity of a
      coding NMNAT1 mutation in two unrelated LCA patients by the identification of two
      distinct heterozygous partial NMNAT1 deletions. Molecular characterization of the
      breakpoint junctions revealed a complex Alu-rich genomic architecture. Our study
      uncovered hidden genetic variation in NMNAT1-associated LCA and emphasized a
      shift from coding to noncoding regulatory mutations and repeat-mediated SVs in
      the molecular pathogenesis of heterogeneous recessive disorders such as
      hereditary blindness. 

PMID- 26316327
TI  - Effect of light on the growth of non-nitrogen-fixing and nitrogen-fixing
      phytoplankton in an aquatic system.
AB  - We discuss a mathematical model of growth of two types of phytoplankton, non
      nitrogen-fixing and nitrogen-fixing, that both require light in order to grow. We
      use general functional responses to represent the inhibitory effect their biomass
      has on the exposure to light. We give conditions for the existence and local
      stability of all of the possible steady-states (die out, single species survival,
      and coexistence). We derive conditions for global stability of the die out and
      single-species steady-states and for persistence of both species when the
      coexistence steady-state exists. Numerical investigation illustrates the
      qualitative dynamics demonstrating that even under constant environmental
      conditions, both stable intrinsic oscillatory behavior and a period doubling
      route to chaotic dynamics are possible. We also show that competitor-mediated
      coexistence can occur due to the positive feedback resulting from recycling by
      the nitrogen-fixing phytoplankton. To show the impact of seasonal change in water
      depth, we also allow the water depth to vary in an annual cycle and discuss echo
      blooms in this context. 

PMID- 26316328
TI  - Brillouin spectroscopy of fluid inclusions proposed as a paleothermometer for
      subsurface rocks.
AB  - As widespread, continuous instrumental Earth surface air temperature records are
      available only for the last hundred fifty years, indirect reconstructions of past
      temperatures are obtained by analyzing "proxies". Fluid inclusions (FIs) present
      in virtually all rock minerals including exogenous rocks are routinely used to
      constrain formation temperature of crystals. The method relies on the presence of
      a vapour bubble in the FI. However, measurements are sometimes biased by surface
      tension effects. They are even impossible when the bubble is absent (monophasic
      FI) for kinetic or thermodynamic reasons. These limitations are common for
      surface or subsurface rocks. Here we use FIs in hydrothermal or geodic quartz
      crystals to demonstrate the potential of Brillouin spectroscopy in determining
      the formation temperature of monophasic FIs without the need for a bubble. Hence,
      this novel method offers a promising way to overcome the above limitations. 

PMID- 26316329
TI  - Regulation of uric acid metabolism and excretion.
AB  - Purines perform many important functions in the cell, being the formation of the
      monomeric precursors of nucleic acids DNA and RNA the most relevant one. Purines
      which also contribute to modulate energy metabolism and signal transduction, are
      structural components of some coenzymes and have been shown to play important
      roles in the physiology of platelets, muscles and neurotransmission. All cells
      require a balanced quantity of purines for growth, proliferation and survival.
      Under physiological conditions the enzymes involved in the purine metabolism
      maintain in the cell a balanced ratio between their synthesis and degradation. In
      humans the final compound of purines catabolism is uric acid. All other mammals
      possess the enzyme uricase that converts uric acid to allantoin that is easily
      eliminated through urine. Overproduction of uric acid, generated from the
      metabolism of purines, has been proven to play emerging roles in human disease.
      In fact the increase of serum uric acid is inversely associated with disease
      severity and especially with cardiovascular disease states. This review describes
      the enzymatic pathways involved in the degradation of purines, getting into their
      structure and biochemistry until the uric acid formation. 

PMID- 26316330
TI  - Recombinant glycoproteins: The impact of cell lines and culture conditions on the
      generation of protein species.
AB  - Glycosylation is the most complex post-translational modification. Thus, it
      contributes to versatile chemical compositions of proteins, leading to high
      amounts of protein species. The structural heterogeneity of glycoproteins was
      also described by the definition of glycoforms. We therefore introduced a new
      term called "glycoprotein species" to join the two concepts from different fields
      of biology. In this study, we further determined the theoretical numbers of
      glycoprotein species of two recombinant glycoproteins - a therapeutical antibody
      and the human protease inhibitor alpha-1-antitrypsin (A1AT) - based on structural
      analysis of their N-glycans. Moreover, we showed that variations in the used cell
      lines and their cultivation conditions strongly influence the number of
      glycoprotein species in case of recombinant A1AT production. BIOLOGICAL
      SIGNIFICANCE: Protein glycosylation is a major source for the huge amount of
      protein species. This study extends the sight of protein species by the following
      contributions: 1) The new term "glycoprotein species" was defined to introduce
      the concept of glycoforms into the field. 2) An estimation of the number of
      potential glycoprotein species of two particular glycoproteins was given. 3) The
      influence of production conditions for recombinant glycoproteins on glycoprotein
      species generation was displayed.

PMID- 26316331
TI  - Paralytic shellfish toxin biosynthesis in cyanobacteria and dinoflagellates: A
      molecular overview.
AB  - Paralytic shellfish toxins (PSTs) are a group of water soluble neurotoxic
      alkaloids produced by two different kingdoms of life, prokaryotic cyanobacteria
      and eukaryotic dinoflagellates. Owing to the wide distribution of these
      organisms, these toxic secondary metabolites account for paralytic shellfish
      poisonings around the world. On the other hand, their specific binding to voltage
      gated sodium channels makes these toxins potentially useful in pharmacological
      and toxicological applications. Much effort has been devoted to the biosynthetic
      mechanism of PSTs, and gene clusters encoding 26 proteins involved in PST
      biosynthesis have been unveiled in several cyanobacterial species. Functional
      analysis of toxin genes indicates that PST biosynthesis in cyanobacteria is a
      complex process including biosynthesis, regulation, modification and export.
      However, less is known about the toxin biosynthesis in dinoflagellates owing to
      our poor understanding of the massive genome and unique chromosomal
      characteristics [1]. So far, few genes involved in PST biosynthesis have been
      identified from dinoflagellates. Moreover, the proteins involved in PST
      production are far from being totally explored. Thus, the origin and evolution of
      PST biosynthesis in these two kingdoms are still controversial. In this review,
      we summarize the recent progress on the characterization of genes and proteins
      involved in PST biosynthesis in cyanobacteria and dinoflagellates, and discuss
      the standing evolutionary hypotheses concerning the origin of toxin biosynthesis
      as well as future perspectives in PST biosynthesis. SCIENTIFIC QUESTION:
      Paralytic shellfish toxins (PSTs) are a group of potent neurotoxins which
      specifically block voltage-gated sodium channels in excitable cells and result in
      paralytic shellfish poisonings (PSPs) around the world. Two different kingdoms of
      life, cyanobacteria and dinoflagellates are able to produce PSTs. However, in
      contrast with cyanobacteria, our understanding of PST biosynthesis in
      dinoflagellates is extremely limited owing to their unique features. The origin
      and evolution of PST biosynthesis in these two kingdoms are still controversial.
      TECHNICAL SIGNIFICANCE: High-throughput omics technologies, such as genomics,
      transcriptomics and proteomics provide powerful tools for the study of PST
      biosynthesis in cyanobacteria and dinoflagellates, and have shown their powerful
      potential with regard to revealing genes and proteins involved in PST
      biosynthesis in two kingdoms. SCIENTIFIC SIGNIFICANCE: This review summarizes the
      recent progress in PST biosynthesis in cyanobacteria and dinoflagellates with
      focusing on the novel insights from omics technologies, and discusses the
      evolutionary relationship of toxin biosynthesis genes between these two kingdoms.

PMID- 26316332
TI  - Primary intraosseous mucoepidermoid carcinoma of the jaw: Reappraisal of The MD
      Anderson Cancer Center experience.
AB  - BACKGROUND: Mucoepidermoid carcinoma arises from major or minor salivary glands,
      making up 10% of salivary gland tumors. Intraosseous mucoepidermoid carcinomas
      are rare, and make up only 2% to 3% of all mucoepidermoid carcinomas. The
      t(11;19) and its CRTC1-MAML2 fusion gene transcript have been identified in
      mucoepidermoid carcinoma and are associated with a subset of mucoepidermoid
      carcinomas. The extent to which the transcript influences disease features and
      patient survival is unclear. METHODS: We conducted a retrospective analysis of
      records for clinical features, surgical interventions, and prognoses. Reverse
      transcriptase-polymerase chain reaction (RT-PCR) and fluorescence in situ
      hybridization (FISH) used to assess the t(11;19) fusion gene in intraosseous
      mucoepidermoid carcinoma. RESULTS: Twenty-five patients with intraosseous
      mucoepidermoid carcinoma treated between 1998 and 2013 were identified. The
      t(11;19) fusion gene transcript CRTC1-MAML2 manifested in 9 intraosseous
      mucoepidermoid carcinomas, whereas is was not detected in another 9 intraosseous
      carcinomas. Although the incidence of this fusion in mucoepidermoid carcinoma
      varies, it is generally accepted that more than 50% of this entity manifest the
      CRTC1-MAML2. CONCLUSION: Intraosseous mucoepidermoid carcinoma diagnosis should
      be based on clinical and pathologic manifestations and complete resection is the
      first choice for patient treatment. The need for neck dissection and adjuvant
      treatment are debatable. Radiotherapy may improve prognosis and may be
      recommended in the postoperative period. Primary intraosseous mucoepidermoid
      carcinoma can manifest the fusion transcript in a subset of tumors. (c) 2015
      Wiley Periodicals, Inc. Head Neck 38: E1312-E1317, 2016.

PMID- 26316334
TI  - Vitamin D deficiency in patients with intestinal malabsorption syndromes--think
      in and outside the gut.
AB  - There is a very high prevalence of vitamin D deficiency, which is defined by a
      serum level of 25-hydroxyvitamin D [25(OH)D] of lower than 20 ng/mL, in all
      populations of the world. Unfortunately, the prevalence of vitamin D deficiency
      in patients with intestinal malabsorption syndromes, including cystic fibrosis
      (CF), celiac disease (CD), short bowel syndrome and inflammatory bowel disease
      (IBD), is higher than that in the general population, indicating the presence of
      disease-specific causative factors. In this review, we aimed to present clinical
      findings to highlight the roles of insufficient exposure to sunlight and
      inflammation in the development of vitamin D deficiency in patients with
      intestinal malabsorption syndromes. Furthermore, we aimed to present experimental
      evidence that supported a role of vitamin D deficiency in the pathogenesis of
      IBD. Finally, we reviewed clinical intervention strategies aiming to normalize
      vitamin D status in and even to improve the conditions of patients and to discuss
      certain issues that needed to be addressed in future research. 

PMID- 26316333
TI  - GADD34-deficient mice develop obesity, nonalcoholic fatty liver disease, hepatic
      carcinoma and insulin resistance.
AB  - The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing in
      parallel with the prevalence of obesity. DNA damage-inducible protein 34
      (GADD34/Ppp1r15a), originally isolated from UV-inducible transcripts in Chinese
      hamster ovary (CHO) cells, dephosphorylates several kinases that function in
      important signaling cascades, including dephosphorylation of eIF2alpha. We
      examined the effects of GADD34 on natural life span by using GADD34-deficient
      mice. Here we observed for the first time that with age GADD34-deficient mice
      become obese, developing fatty liver followed by liver cirrhosis, hepatocellular
      carcinoma, and insulin resistance. We found that myofibroblasts and immune cells
      infiltrated the portal veins of aged GADD34-deficient mouse livers. A high-fat
      diet (HFD) induced a higher level of steatosis in young GADD34-deficient mice
      compared with WT mice. Differentiation into fat is dependent on insulin
      signaling. Insulin signaling in young GADD34-deficient mice was higher than that
      in WT mice, which explained the higher fat differentiation of mouse embryonic
      fibroblasts (MEFs) observed in GADD34-deficient mice. Through aging or a HFD,
      insulin signaling in GADD34-deficient liver converted to be down regulated
      compared with WT mice. We found that a HFD or palmitate treatment converted
      insulin signaling by up-regulating TNF-alpha and JNK. 

PMID- 26316335
TI  - Starch digestibility, energy utilization, and growth performance of broilers fed
      corn-soybean basal diets supplemented with enzymes.
AB  - A study was conducted to evaluate the effects of dietary alpha-amylase and beta
      xylanase supplementation of corn-soy diets, formulated with or without
      supplemental phytase, on growth performance, energy utilization, and starch
      digestibility in broiler chickens. A total of 336 slow-feathering, Cobb * Cobb
      500 male broilers were randomly distributed to 6 treatments having 8 replicates
      of 7 birds each. Birds were fed a common starter diet to d 14 post-hatch (3,050
      kcal/kg AMEn, 21.7% CP, 1.05% Ca, and 0.53% nPP). The experimental diets were
      provided afterwards until d 25. A 2 * 3 factorial arrangement of 2 control diets
      (basal = corn-soy diet without added phytase or PHY = corn-soy diet formulated
      with 1,000 phytase units/kg) and 3 carbohydrase supplementations (0, 80 kilo-Novo
      alpha-amylase units/kg, or 80 kilo-Novo alpha-amylase units/kg + 100 fungal beta
      xylanase units/kg) was used from d 14 to 25. Excreta were collected from 21 to 24
      d and all birds were euthanized at 25 d for jejunum and ileum content collection.
      Samples of feed, excreta, and jejunal and ileal digesta were analyzed for
      determination of total tract retention and ileal apparent digestibility. No
      interactions between diet and carbohydrase were observed. Broilers fed diets
      formulated with phytase or supplemented with amylase + xylanase had higher BW
      gain (BWG) and lower FCR (P < 0.05) when compared with birds fed diets without
      carbohydrases. Relative to the basal diet, AMEn was increased (P < 0.01) by 70
      kcal/kg and 99 kcal/kg when birds were fed the diet supplemented with amylase and
      amylase + xylanase, respectively. Starch digestibility in the jejunum and ileum
      was increased (P < 0.05) by 3.5% and 2.4%, respectively, when birds were fed the
      diet supplemented with amylase + xylanase. Results from this experiment show that
      corn-soy diets having phytase and supplemented with amylase and xylanase led to
      increased growth performance, AMEn, and starch digestibility in broilers.
      Furthermore, the efficacy of exogenous amylase and xylanase was independent of
      the presence of microbial phytase. 

PMID- 26316336
TI  - The effect of allopurinol administration on mitochondrial respiration and gene
      expression of xanthine oxidoreductase, inducible nitric oxide synthase, and
      inflammatory cytokines in selected tissues of broiler chickens.
AB  - Birds have a remarkable longevity for their body size despite an increased body
      temperature, higher metabolic rate, and increased blood glucose concentrations
      compared to most mammals. As the end-product of purine degradation, uric acid
      (UA) is generated in the xanthine/hypoxanthine reactions catalyzed by xanthine
      oxidoreductase (XOR). In the first study, Cobb * Cobb broilers (n = 12; 4 weeks
      old) were separated into 2 treatments (n = 6); control (CON) and allopurinol (AL)
      35 mg/kg BW (ALLO). The purpose of this study was to assess mitochondrial
      function in broiler chickens in response to potential oxidative stress generated
      from the administration of AL for 1 wk. There was a significant reduction in
      state 3 respiration (P = 0.01) and state 4 respiration (P = 0.007) in AL-treated
      birds compared to the controls. The purpose of the second study was to assess the
      effect of AL on gene expression of inflammatory cytokines interferon-gamma (IFN)
      gamma, IL-1beta, IL-6, and IL-12p35, as well as inducible nitric oxide synthase
      and XOR in liver tissue. Cobb * Cobb broilers were separated into two groups at 4
      wk age (n = 10); CON and ALLO. After 1 wk AL treatment, half of the birds in each
      group (CON 1 and ALLO 1) were euthanized while the remaining birds continued on
      AL treatment for an additional week (CON 2 and ALLO 2). A significant increase in
      gene expression of XOR, IFN-gamma, IL-1beta, and IL-12p35 in ALLO 2 birds as
      compared to birds in CON 2 was detected. Liver UA content was significantly
      decreased in both ALLO 1(P = 0.003) and ALLO 2 (P = 0.012) birds when compared to
      CON 1 and CON 2, respectively. The AL reduced liver UA concentrations and
      increased expression of inflammatory cytokines. Additional studies are needed to
      determine if AL causes a direct effect on mitochondria or if mitochondrial
      dysfunction observed in liver mitochondria was due indirectly through increased
      oxidative stress or increased inflammation. 

PMID- 26316337
TI  - Thermal manipulation during embryogenesis affects myoblast proliferation and
      skeletal muscle growth in meat-type chickens.
AB  - Thermal manipulation (TM) of 39.5 degrees C applied during mid-embryogenesis
      (embryonic d 7 to 16) has been proven to promote muscle development and enhance
      muscle growth and meat production in meat-type chickens. This study aimed to
      elucidate the cellular basis for this effect. Continuous TM or intermittent TM
      (for 12 h/d) increased myoblast proliferation manifested by higher (25 to 48%)
      myoblast number in the pectoral muscles during embryonic development but also
      during the first week posthatch. Proliferation ability of the pectoral-muscle
      derived myoblasts in vitro was significantly higher in the TM treatments until
      embryonic d 15 (intermittent TM) or 13 (continuous TM) compared to that of
      controls, suggesting increased myogenic progeny reservoir in the muscle. However,
      the proliferation ability of myoblasts was lower in the TM treatments vs. control
      during the last days of incubation. This coincided with higher levels of myogenin
      expression in the muscle, indicating enhanced cell differentiation in the TM
      muscle. A similar pattern was observed posthatch: Myoblast proliferation was
      significantly higher in the TM chicks relative to controls during the peak of
      posthatch cell proliferation until d 6, followed by lower cell number 2 wk
      posthatch as myoblast number sharply decreases. Higher myogenin expression was
      observed in the TM chicks on d 6. This resulted in increased muscle growth,
      manifested by significantly higher relative weight of breast muscle in the embryo
      and posthatch. It can be concluded that temperature elevation during mid-term
      embryogenesis promotes myoblast proliferation, thus increasing myogenic progeny
      reservoir in the muscle, resulting in enhanced muscle growth in the embryo and
      posthatch. 

PMID- 26316338
TI  - Influence of feeding alternative fiber sources on the gastrointestinal
      fermentation, digestive enzyme activities and mucosa morphology of growing
      Greylag geese.
AB  - The objective of this trial was to study the influence of dietary fiber sources
      on the gastrointestinal fermentation, digestive enzyme activity, and mucosa
      morphology of growing Greylag geese. In total, 240 Greylag geese (28-day-old)
      were allocated to 4 treatments (15 pens/treatment) differing in dietary fiber
      source: corn straw silage (CSS group), steam-exploded corn straw (SECS group),
      steam-exploded wheat straw (SEWS group), or steam-exploded rice straw (SERS
      group). At 112 days of age, 15 birds per group were euthanized to collect
      samples. No difference (P > 0.05) was found on all the gastrointestinal pH values
      and ammonia-nitrogen concentrations between the groups. The CSS and SERS groups
      had a lower (P < 0.05) proportion of acetic acid in the gizzard than the SECS and
      SEWS groups. The CSS group had a higher VFA concentration in the jejunum (P <
      0.05) and acetic acid proportion (P < 0.01) in the ceca, and a lower (P < 0.01)
      butyric acid proportion than the other groups except for the SECS group. The SECS
      group had a higher (P < 0.01) acetic acid proportion and lower (P < 0.05)
      proportions of propionic acid and valeric acid in the ceca than the SEWS and SERS
      groups. Different fiber sources resulted in different VFA profiles, especially in
      the gizzard and ceca. Almost all gastrointestinal protease activities of the CSS
      group were higher (P < 0.05) than the other groups, along with lower (P < 0.01)
      amylase activities in the duodenum, jejunum, ileum, and ceca. Lipase activity in
      proventriculus was highest (P < 0.01) in the SEWS group and its cecal activity
      was lower (P < 0.01) in the SECS and SEWS groups than the CSS and SERS groups
      with a higher (P < 0.01) lipase activity in the CSS group than the SERS group.
      The SECS and SERS groups had a higher cellulase activity in the ceca than the CSS
      and SEWS groups, with a higher (P < 0.01) rectal cellulase activity in the SERS
      group than the other groups. There was no significant effect (P > 0.05) on the
      intestinal mucosa morphology. These results suggest that corn straw silage
      improves protein digestion while steam-exploded straw provides more energy.

PMID- 26316339
TI  - Changing the incubation temperature during embryonic myogenesis influences the
      weight performance and meat quality of male and female broilers.
AB  - Eggs of broilers were initially incubated at 37.8 degrees C, then at 38.8 degrees
      C (group H) and 36.8 degrees C (group L) between embryonic days 7 to 10 (time A)
      and days 10 to 13 (time B) and further incubated at 37.8 degrees C until
      hatching. The chicks were fattened until day 35 and then slaughtered. The effect
      of treatment, time, and sex and their interactions on carcass and meat quality
      traits were determined. No significant impact of the "treatment time" was
      analysed, but "treatment" and "sex" and their interactions influenced (P < 0.05)
      the different parameters. After hatching, group L broilers were heavier (P <
      0.05), followed by slower growth compared to group H chicken. At slaughter day,
      body, carcass, and leg weights of group H broiler were higher (P < 0.05) and
      yield results lower (P < 0.05) compared to group L animals. pH, drip loss, shear
      force, and lightness values of group H broiler breast muscles were higher (P <
      0.05) and grill loss and redness values lower (P < 0.05) compared to group L
      Musculus pectoralis superficialis (MPS). Body, carcass, MPS, and leg weights, leg
      yields and grill loss and lightness values of the male broiler were higher (P <
      0.05) and drip loss results lower (P < 0.05) than the female birds. Male group H
      broiler showed lower (P < 0.05) carcass and MPS yields compared to the control
      and group L males, whereas females group H birds had higher (P < 0.05) carcass
      and MPS weights and lower leg yields (P < 0.05) than the female group L animals.
      The study shows that an increasing incubation temperature during early
      embryogenesis positively influences the growth and carcass traits of the
      broilers, accompanied with a partly negative impact on meat quality (drip loss,
      shear force, lightness). The growth effects were sex-dependent, as significant
      weight differences could be only found in female broilers. The results indicate
      that incubation temperature alteration influences molecular mechanisms in the
      muscle and other tissues with an impact on growth after hatch. 

PMID- 26316340
TI  - Ultrasonic eggshell thickness measurement for selection of layers.
AB  - This study aimed to develop a methodology for using ultrasonic technology (USG)
      to record eggshell thickness for selection of layers. Genetic correlations
      between eggshell strength and its thickness have been reported to be around 0.8,
      making shell thickness a selection index candidate element. Applying ultrasonic
      devices to measure shell thickness leaves an egg intact for further handling. In
      this study, eggs from 2 purebred populations of Rhode Island White (RIW) and
      Rhode Island Red (RIR) hens were collected on a single day in the 33rd week of
      the farm laying calendar from 2,414 RIR and 4,525 RIW hens. Beginning from the
      large end of the egg, measurements were taken at 5 latitudes: 0o (USG0), 45o
      (USG45), 90o (USG90), 135o (USG135), and 180o (USG180). To estimate the
      repeatability of readings, measurements were repeated at each parallel on 3
      meridians. Electronic micrometer measurement ( EMM: ) were taken with an
      electronic micrometer predominantly at the wider end of eggs from 2,397 RIR and
      4,447 RIW hens. A multiple-trait statistical model fit the fixed effect of year
      of-hatch * hatch-within-year, and random effects due to repeated measurements
      (except EMM) and an animal's additive genetic component. The shell was thinnest
      in the region where chicks break it upon hatching (USG0, USG45). Heritabilities
      of shell thickness in different regions of the shell ranged from 0.09 to 0.19
      (EMM) in RIW and from 0.12 to 0.23 (EMM) in RIR and were highest for USG45 and
      USG0. Because the measurement repeatabilities were all above 0.90, our
      recommendation for balancing egg strength against hatching ease is to take a
      single measurement of USG45. Due to high positive genetic correlations between
      shell thickness in different regions of the shell its thickness in the pointed
      end region will be modified accordingly, in response to selection for USG45. 

PMID- 26316341
TI  - Effects of dietary fiber on cecal short-chain fatty acid and cecal microbiota of
      broiler and laying-hen chicks.
AB  - This experiment was conducted to evaluate the effects of feeding dietary fiber on
      cecal short-chain fatty acid (SCFA) concentration and cecal microbiota of broiler
      and laying-hen chicks. The lower fiber diet was based on corn-soybean meal (SBM)
      and the higher fiber diet was formulated using corn-SBM-dried distillers grains
      with solubles (DDGS) and wheat bran to contain 60.0 g/kg of both DDGS and wheat
      bran from 1 to 12 d and 80.0 g/kg of both DDGS and wheat bran from 13 to 21 d.
      Diets were formulated to meet or exceed NRC nutrient requirements. Broiler and
      laying-hen chicks were randomly assigned to the high and low fiber diets with 11
      replicates of 8 chicks for each of the 4 treatments. One cecum from 3 chicks was
      collected from each replicate: one cecum underwent SCFA concentration analysis,
      one underwent bacterial DNA isolation for terminal restriction fragment length
      polymorphism (TRFLP), and the third cecum was used for metagenomics analyses.
      There were interactions between bird line and dietary fiber for acetic acid (P =
      0.04) and total SCFA (P = 0.04) concentration. There was higher concentration of
      acetic acid (P = 0.02) and propionic acid (P < 0.01) in broiler chicks compared
      to laying-hen chicks. TRFLP analysis showed that cecal microbiota varied due to
      diet (P = 0.02) and chicken line (P = 0.03). Metagenomics analyses identified
      differences in the relative abundance of Helicobacter pullorum and Megamonas
      hypermegale and the genera Enterobacteriaceae, Campylobacter, Faecalibacterium,
      and Bacteroides in different treatment groups. These results provide insights
      into the effect of dietary fiber on SCFA concentration and modulation of cecal
      microbiota in broiler and laying-hen chicks. 

PMID- 26316342
TI  - Standardized Ileal Amino Acid Digestibility of Corn, Corn Distillers' Dried
      Grains with Solubles, Wheat Middlings, and Bakery By-Products in Broilers and
      Laying Hens.
AB  - Standardized ileal amino acid digestibility (SIAAD) of 5 samples of corn
      distillers dried grain with solubles (DDGS), 5 samples of bakery by-products
      (BBP), 3 samples of corn, and 1 sample of wheat middlings (WM) were evaluated in
      broilers and laying hens. Diets containing each of the 14 feed ingredients were
      evaluated in 21 day-old broiler chickens. The DDGS and BBP containing diets were
      fed to 30-week-old laying hens, while corn and wheat middling were evaluated in
      50-week-old laying hens. All the diets were semi-purified with each feed
      ingredient being the only source of amino acid (AA). To obtain SIAAD values,
      apparent ileal AA digestibility was corrected for basal ileal endogenous AA
      losses using values generated from broilers and laying hens fed a nitrogen-free
      diet. Ileal crude protein digestibility for the 5 DDGS samples was higher (P <
      0.05) in broilers than in laying hens. Broilers had higher SIAAD for DDGS 2, 3,
      4, and 5 while there was no difference for DDGS 1 except for 4 AA where broilers
      had higher (P < 0.05) SIAAD values. Standardized ileal AA digestibility values
      for broilers were higher (P < 0.05) for BBP 1 and 4. Ileal CP digestibility for
      corn 1 was higher (P < 0.05) for broilers compared to laying hens, and SIAAD
      values for the 16 AA (9 indispensable and 7 dispensable) evaluated in this study
      were higher (P < 0.05) in broilers. Broilers had higher (P < 0.05) SIAAD values
      for 4 (histidine, leucine, phenylalanine, and valine) and 6 (histidine, leucine,
      methionine, phenylalanine, threonine, and valine) indispensable and 3 (cysteine,
      glutamic acid, and proline) and 4 (cysteine, glutamic acid, proline, and serine)
      dispensable AA for corn 2 and corn 3, respectively. No difference in SIAAD
      between broilers and laying hens was observed for WM. Results from this study
      confirm that high variability in digestibility exists between different samples
      of DDGS. Differences in SIAAD between broilers and laying hens were observed in
      some samples of DDGS and BBP. 

PMID- 26316343
TI  - The effect of different degrees of feed restriction on heat shock protein 70,
      acute phase proteins, and other blood parameters in female broiler breeders.
AB  - The aim of the current study was to determine the physiological response to feed
      restriction in female broiler breeders using a range of conventional and novel
      indicators. One hundred female breeders were subjected to one of five feeding
      regimens from d 28 to 42 as follows (i) ad libitum feeding (AL), (ii-v) 75, 60,
      45, and 30% of ad libitum feed intake. Blood heterophil to lymphocyte ratio
      (HLR), and plasma circulating corticosterone (CORT), ghrelin (GHR), serotonin (5
      HT), and dopamine (DA) and serum acute phase proteins (APP) concentrations
      together with brain heat shock protein (HSP) 70 level were measured. The results
      showed a significant effect of feed restriction on blood HLR and plasma CORT,
      GHR, 5-HT, DA, and brain HSP 70 levels. However, feed restriction had no effect
      on serum levels of APP of alpha-1 acid glycoprotein, ovotransferin, and
      ceruloplasmin. Serum levels of 5-HT and GHR varied curvilinearly with the feed
      restriction level. The relationship between brain HSP 70 and level of feed
      restriction was negligible. However, significant linear relationships between
      HLR, CORT, DA, and the level of feed restriction were noted. Thus, these 3
      parameters appear to represent a straight forward relation with severity of feed
      restriction. 

PMID- 26316344
TI  - Relationships Between Imaging Assessments and Outcomes in Solitaire With the
      Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic
      Stroke.
AB  - BACKGROUND AND PURPOSE: Imaging findings can predict outcomes in patients with
      acute stroke. Relationships between imaging findings and clinical and imaging
      outcomes in patients randomized to intravenous tissue-type plasminogen activator
      alone versus tissue-type plasminogen activator plus endovascular therapy
      (Solitaire device) in the Solitaire With the Intention for Thrombectomy as
      Primary Endovascular Treatment for Acute Ischemic Stroke (SWIFT PRIME) study were
      assessed. METHODS: We evaluated associations between imaging assessments
      (baseline mismatch profiles/ischemic core volumes and successful reperfusion)
      with imaging outcomes (27-hour infarct volume/growth) and clinical outcomes
      (modified Rankin Scale scores at 90 days). Imaging variables that predict
      favorable clinical outcomes were assessed in both univariate and multivariate
      models. RESULTS: One hundred and ninety-five patients were included. Successful
      reperfusion and infarct volume (assessed at 27 hours) were powerful independent
      predictors of favorable clinical outcomes (modified Rankin Scale score of 0-2 at
      90 days). Patients with the target mismatch profile at baseline had a higher rate
      of reperfusion, lesser infarct growth, smaller infarct volumes, and better
      clinical outcomes in the Solitaire plus tissue-type plasminogen activator
      (intervention) group than those in the tissue-type plasminogen activator-alone
      (control) group. Patients with larger mismatch volumes at baseline had a trend
      toward better treatment response in the intervention group than patients who had
      smaller (<50 mL) mismatch volumes. CONCLUSIONS: Patients who achieved reperfusion
      had substantially more favorable clinical and imaging outcomes in both the
      intervention and the control groups. Infarct volume at 27 hours strongly
      correlated with clinical outcome at 90 days in both treatment groups. SWIFT PRIME
      patients with the target mismatch profile had a highly favorable response to
      endovascular therapy on both clinical and imaging outcomes. Both reperfusion and
      infarct volumes at 27 hours were powerful and independent predictors of 90-day
      clinical outcomes. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01657461.

PMID- 26316345
TI  - Clinical and Economic Implications of Apixaban Versus Aspirin in the Low-Risk
      Nonvalvular Atrial Fibrillation Patients.
AB  - BACKGROUND AND PURPOSE: Although recommended by guidelines, the benefits of
      treating patients with atrial fibrillation with a low-stroke risk score, with
      aspirin or anticoagulants, have not been clearly established. With advent of
      safer non-vitamin K antagonist oral anticoagulant, we assessed the clinical and
      economic implications of 5 mg BID of apixaban versus aspirin among patients with
      a relative low risk of stroke as assessed using the CHADS2 (congestive heart
      failure, hypertension, age>75, diabetes mellitus, stroke/transient ischemic
      attack) and CHA2DS2-VASc (congestive heart failure, hypertension, age, diabetes
      mellitus, stroke/transient ischemic attack, vascular disease) stroke risk
      classification. METHODS: A previously developed and validated Markov model was
      adapted. A secondary analysis of the Apixaban Versus Acetylsalicylic Acid to
      Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable
      for Vitamin K Antagonist Treatment (AVERROES) study was conducted to estimate
      event rates in different low-risk cohorts by treatment. Three cohorts (n=1000)
      with a CHADS2 score of 1, CHA2DS2-VASc score of 1, and CHA2DS2-VASc of score 2 to
      4 were simulated to assess the number of clinical events avoided in terms of
      strokes and major bleeds, as well as life years gained, quality-adjusted life
      years gained, costs, and incremental costs per quality-adjusted life year gained.
      RESULTS: Apixaban was associated with fewer strokes and systemic embolism versus
      aspirin across all subgroups; however, it caused more major bleeding events. The
      reduction in systemic embolism offset the increase in major bleeding events
      leading to increased life expectancy and quality-adjusted life year gains,
      achieved at an increased cost that was lower than the UK threshold of $44,400
      (ie, L30,000) per quality-adjusted life year gained across the 3 cohorts
      examined. CONCLUSIONS: Anticoagulant treatment with apixaban versus aspirin in
      low-risk patients, as identified using CHADS2 or CHA2DS2-VASc, is projected to
      increase life expectancy and provide clinical benefits that are cost effective.

PMID- 26316347
TI  - Insufficient Evidence of Purported Lunar Effect on Pollination in Ephedra.
AB  - It has been suggested that the timing of pollination in Ephedra foeminea
      coincides with the full moon in July. The implication is that the plant can
      detect the full moon through light or gravity and that this trait is an
      evolutionary adaptation that aids the navigation by pollinating insects. Here we
      show that there are insufficient data to make such a claim, and we predict that
      pollinations of E. foeminea do not in general coincide with the full moon. 

PMID- 26316346
TI  - Rapid Assessment and Treatment of Transient Ischemic Attacks and Minor Stroke in
      Canadian Emergency Departments: Time for a Paradigm Shift.

PMID- 26316348
TI  - Reconstructing A/B compartments as revealed by Hi-C using long-range correlations
      in epigenetic data.
AB  - Analysis of Hi-C data has shown that the genome can be divided into two
      compartments called A/B compartments. These compartments are cell-type specific
      and are associated with open and closed chromatin. We show that A/B compartments
      can reliably be estimated using epigenetic data from several different platforms:
      the Illumina 450 k DNA methylation microarray, DNase hypersensitivity sequencing,
      single-cell ATAC sequencing and single-cell whole-genome bisulfite sequencing. We
      do this by exploiting that the structure of long-range correlations differs
      between open and closed compartments. This work makes A/B compartment assignment
      readily available in a wide variety of cell types, including many human cancers. 

PMID- 26316349
TI  - A one-handed maneuver for opening the airway during flexible bronchoscopy under
      deep sedation.

PMID- 26316350
TI  - Pressure ulcer risk assessment: retrospective analysis of Braden Scale scores in
      Portuguese hospitalised adult patients.
AB  - AIMS AND OBJECTIVES: To analyse the Braden Scale scores and sub-scores assessed
      in Portuguese hospitalised adult patients in association with their
      characteristics, diagnoses and length of stay. BACKGROUND: The Braden Scale is
      used worldwide for pressure ulcer risk assessment and supports nurses in the
      implementation of preventive interventions. DESIGN: Retrospective cohort analysis
      of electronic health record database from adult patients admitted to medical and
      surgical areas during 2012. METHODS: Braden Scale scores and sub-scores of 8147
      patients were associated with age, gender, type of admission (emergency service
      or programmed), specialty units (medical or surgical), length of stay, patient
      discharge (discharge, decease or transference to other hospital) and ICD-9
      diagnosis. RESULTS: The participants with significantly lower Braden Scale scores
      were women, older people, hospitalised in medical units, with emergency service
      admission, longer hospitalisation stays and/or with vascular, traumatisms,
      respiratory, infection or cardiac diseases. Mobility, friction/shear forces and
      activity had higher contributions to the Braden Scale score, while nutrition had
      the lowest contribution. CONCLUSIONS: Approximately one-third of all participants
      had high risk of pressure ulcer development at admission, which led to the
      application of nursing preventive care. Our study demonstrated that nurses should
      pay special attention to patients over 50 years of age, who had significantly
      lower Braden Scale scores. The Braden Scale scores significantly increased in the
      last assessments showing that Braden Scale is sensitive to the clinical
      improvement of the patient. Braden Scale correlations with length of stay reveal
      its importance as predictor of length of stay. RELEVANCE TO CLINICAL PRACTICE:
      Nurses should use Braden Scale assessment and consider patients' characteristics
      and diagnoses to plan more focused preventive interventions and improve nursing
      care. This study could be the first step to create a preventive protocol based on
      institutional reality, patients' characteristics, level of risk and affected sub
      scales.

PMID- 26316352
TI  - Preface: Issue 29.8: Best Practice.

PMID- 26316351
TI  - High-frequency focal repetitive cerebellar stimulation induces prolonged
      increases in human pharyngeal motor cortex excitability.
AB  - KEY POINTS: Neurostimulation is a rapidly emerging approach to swallowing
      rehabilitation, but cerebellar stimulation has not been explored as a treatment.
      Such proposed therapies for post-stroke dysphagia have required confirmation of
      physiological effects and optimisation of parameters in healthy humans prior to
      translational progression into patient groups. There is strong evidence for a
      role of the cerebellum in swallowing physiology, but this relationship has been
      under-explored. Recently, single pulses of cerebellar magnetic stimulation have
      been shown to directly evoke responses from pharyngeal musculature and produce
      short-term enhancement of cortico-pharyngeal motor evoked potentials, suggesting
      the feasibility of a cerebellar approach to neurostimulation in the swallowing
      system. We therefore examined multiple parameters of repetitive cerebellar
      magnetic stimulation and have described the optimal settings to provoke longer
      lasting changes in swallowing neurophysiology. Based on evidence from the post
      stroke dysphagia neurostimulation literature, these changes may have a
      therapeutic potential for swallowing rehabilitation. ABSTRACT: Brain
      neurostimulation has been shown to modulate cortical swallowing neurophysiology
      in post-stroke dysphagia with therapeutic effects which are critically dependent
      on the stimulation parameters. Cerebellar neurostimulation is, however, a novel,
      unexplored approach to modulation of swallowing pathways as a prelude to therapy
      for dysphagia. Here, we randomised healthy human subjects (n = 17) to receive one
      of five cerebellar repetitive TMS (rTMS) interventions (Sham, 1 Hz, 5 Hz, 10 Hz
      and 20 Hz) on separate visits to our laboratory. Additionally, a subset of
      subjects randomly received each of three different durations (50, 250, 500
      pulses) of optimal frequency versus sham cerebellar rTMS. Prior to interventions
      subjects underwent MRI-guided single-pulse transcranial magnetic stimulation
      (TMS) to co-localise pharyngeal and thenar representation in the cortex and
      cerebellum (midline and hemispheric) before acquisition of baseline motor evoked
      potential (MEP) recordings from each site as a measure of excitability. Post
      interventional MEPs were recorded for an hour and compared to sham using repeated
      measures ANOVA. Only 10 Hz cerebellar rTMS increased cortico-pharyngeal MEP
      amplitudes (mean bilateral increase 52%, P = 0.007) with effects lasting 30 min
      post-intervention with an optimal train length of 250 pulses (P = 0.019). These
      optimised parameters of cerebellar rTMS can produce sustained increases in
      corticobulbar excitability and may have clinical translation in future studies of
      neurogenic dysphagia.

PMID- 26316353
TI  - Nodular Scleroderma.

PMID- 26316354
TI  - Lean rats gained more body weight than obese ones from a high-fibre diet.
AB  - There is controversy over previous findings that a high ratio of Firmicutes to
      Bacteriodetes helps obese animals harvest energy from the diet. To further
      investigate the relationship between microbial composition and energy harvest,
      microbial adaptation to diet and time should be considered. In this study, lean
      and obese rats were successfully induced with low-fat and high-fat diets. An 8
      week high soyabean fibre (HSF)-containing diet was then fed to investigate the
      interaction between the diet and the rats' gut microbiota, as well as their
      influence on rats' growth. Rats' body weight (BW) was recorded weekly; their
      plasma lipids and their gut microbiota at week 11, 15 and 19 were analysed. After
      the consumption of the HSF diet, BW of lean rats increased significantly
      (P<0.05), but no significant alteration in BW was found in obese rats. The
      average content of plasma cholesterol was lowered and that of TAG was upgraded in
      both the groups when fed the HSF diet. There was no significant difference
      observed at each period between lean and obese rats. In the group of lean rats,
      the diversity of gut microbiota was elevated strongly (P<0.01), and bacteria from
      phylum Firmicutes and Bacteroidetes were both increased largely (P<0.01);
      however, the bacterial diversity and composition in obese rats were less altered
      after the HSF diet control. In conclusion, the increased Firmicutes and
      Bacteriodetes might relate to lean rats' higher BW gain; 'obese microbiota' could
      not help the hosts harvest more energy from the HSF diet. 

PMID- 26316355
TI  - Can the Neutrophil-to-Lymphocyte Ratio Appropriately Predict Carotid Artery
      Stenosis in Patients with Ischemic Stroke?-A Retrospective Study.
AB  - BACKGROUND: Carotid stenosis is a risk factor in ischemic stroke. Although C
      reactive protein, interleukin-6, and tumor necrosis factor-alpha are known to
      predict carotid atherosclerosis, they are difficult to obtain in clinical
      practice. By studying the association between neutrophil-to-lymphocyte ratio
      (NLR) and carotid artery intima-media thickening (IMT) in patients with ischemic
      stroke, we determined that the NLR can predict carotid stenosis. METHODS: We
      selected 252 patients with acute to subacute ischemic stroke who underwent
      carotid ultrasonography and complete and differential blood cell count tests. We
      collected data on sex, age, body mass index (BMI), alcohol consumption, smoking,
      hypertension, diabetes mellitus, dyslipidemia, and heart disease. Male and female
      patients were analyzed separately. We divided the subjects into 2 groups
      according to carotid IMT, and compared baseline characteristics and NLR between
      the 2 groups. The regression analysis was adjusted for confounding factors such
      as age, BMI, NLR, smoking, alcohol consumption, and a medical history of
      hypertension, diabetes mellitus, dyslipidemia, or heart disease. RESULTS: Carotid
      IMT tended to significantly increase with NLR and age in men and with age in
      women. In men, multiple linear regression analyses adjusted for confounding
      factors showed that NLR (P < 0.001) and age (P = 0.001) had a significant
      positive association with carotid IMT (adjusted R(2) = 0.185, root mean squared
      error [MSE] = 0.152). However, no parameters showed significant positive
      associations in women. CONCLUSION: NLR can be a clinically significant predictor
      of the degree of carotid stenosis in male patients with ischemic stroke. However,
      additional studies are required to obtain more concrete results.

PMID- 26316356
TI  - Research of Sleep Disorders in Patients with Acute Cerebral Infarction.
AB  - BACKGROUND: The purpose of this study is to investigate the incidence of sleep
      disorders (SD), characteristic of cerebral infarction patients with different
      parts affected. METHODS: The research selected 101 patients with a first
      occurrence of acute cerebral infarction as the experimental group, and 86
      patients without cerebral infarction as controls. Polysomnography, Pittsburgh
      Sleep Quality Index, Epworth Sleepiness Scale, and US National Stroke Scale were
      assessed. RESULTS: Compared with control group, the incidence of SD was higher in
      experimental group (P < .05), and the incidence of SD in women was more frequent
      in experimental group (P < .05). There was no significant difference in the types
      of SD patients with acute cerebral infarction. In addition, the sleep quality of
      cerebral infarction patients with different parts affected was different: the
      sleep quality of left hemisphere infarction patients was poor compared with the
      right one, and the sleep quality of anterior circulation patients was poor
      compared with posterior circulation patients. Patients with thalamus infarction
      had a longer sleep time and a shorter sleep latency and stage 2 of non-rapid eye
      movement sleep compared with non-thalamus infarction group. CONCLUSIONS: The
      prevalence of SD was relatively high in acute cerebral infarction patients, and
      the detailed classification of acute cerebral infarction may provide a more
      effective therapeutic method and therefore relieve patients' pain and supply a
      better quality of sleep.

PMID- 26316357
TI  - The venous lymph-node flap.

PMID- 26316359
TI  - Sustained neurological recovery induced by resveratrol is associated with
      angioneurogenesis rather than neuroprotection after focal cerebral ischemia.
AB  - According to the French paradox, red wine consumption reduces the incidence of
      vascular diseases even in the presence of highly saturated fatty acid intake.
      This phenomenon is widely attributed to the phytoalexin resveratrol, a red wine
      ingredient. Experimental studies suggesting that resveratrol has neuroprotective
      properties mostly used prophylactic delivery strategies associated with short
      observation periods. These studies did not allow conclusions to be made about
      resveratrol's therapeutic efficacy post-stroke. Herein, we systematically
      analyzed effects of prophylactic, acute and post-acute delivery of resveratrol
      (50mg/kg) on neurological recovery, tissue survival, and angioneurogenesis after
      focal cerebral ischemia induced by intraluminal middle cerebral artery occlusion
      in mice. Over an observation period of four weeks, only prolonged post-acute
      resveratrol delivery induced sustained neurological recovery as assessed by rota
      rod, tight rope and corner turn tests. Although prophylactic and acute
      resveratrol delivery reduced infarct volume and enhanced blood-brain-barrier
      integrity at 2 days post-ischemia by elevating resveratrol's downstream signal
      sirtuin-1, increasing cell survival signals (phosphorylated Akt, heme oxygenase
      1, Bcl-2) and decreasing cell death signals (Bax, activated caspase-3), a
      sustained reduction of infarct size on day 28 was not observed in any of the
      three experimental conditions. Instead, enhanced angiogenesis and neurogenesis
      were noted in animals receiving post-acute resveratrol delivery, which were
      associated with elevated concentrations of GDNF and VEGF in the brain. Thus,
      sustained neurological recovery induced by resveratrol depends on successful
      brain remodeling rather than structural neuroprotection. The recovery promoting
      effect of delayed resveratrol delivery opens promising perspectives for stroke
      therapy.

PMID- 26316358
TI  - Genetic targeting of protease activated receptor 2 reduces inflammatory
      astrogliosis and improves recovery of function after spinal cord injury.
AB  - Inflammatory-astrogliosis exacerbates damage in the injured spinal cord and
      limits repair. Here we identify Protease Activated Receptor 2 (PAR2) as an
      essential regulator of these events with mice lacking the PAR2 gene showing
      greater improvements in motor coordination and strength after compression-spinal
      cord injury (SCI) compared to wild type littermates. Molecular profiling of the
      injury epicenter, and spinal segments above and below, demonstrated that mice
      lacking PAR2 had significantly attenuated elevations in key hallmarks of
      astrogliosis (glial fibrillary acidic protein (GFAP), vimentin and neurocan) and
      in expression of pro-inflammatory cytokines (interleukin-6 (IL-6), tumor necrosis
      factor (TNF) and interleukin-1 beta (IL-1beta)). SCI in PAR2-/- mice was also
      accompanied by improved preservation of protein kinase C gamma (PKCgamma)
      immunopositive corticospinal axons and reductions in GFAP-immunoreactivity,
      expression of the pro-apoptotic marker BCL2-interacting mediator of cell death
      (BIM), and in signal transducer and activator of transcription 3 (STAT3). The
      potential mechanistic link between PAR2, STAT3 and astrogliosis was further
      investigated in primary astrocytes to reveal that the SCI-related serine
      protease, neurosin (kallikrein 6) promotes IL-6 secretion in a PAR2 and STAT3
      dependent manner. Data point to a signaling circuit in primary astrocytes in
      which neurosin signaling at PAR2 promotes IL-6 secretion and canonical STAT3
      signaling. IL-6 promotes expression of GFAP, vimentin, additional IL-6 and robust
      increases in both neurosin and PAR2, thereby driving the PAR2-signaling circuit
      forward. Given the significant reductions in astrogliosis and inflammation as
      well as superior neuromotor recovery observed in PAR2 knockout mice after SCI, we
      suggest that this receptor and its agonists represent new drug targets to foster
      neuromotor recovery. 

PMID- 26316360
TI  - Tonic and phasic co-variation of peripheral arousal indices in infants.
AB  - Tonic and phasic differences in peripheral autonomic nervous system (ANS)
      indicators strongly predict differences in attention and emotion regulation in
      developmental populations. However, virtually all previous research has been
      based on individual ANS measures, which poses a variety of conceptual and
      methodlogical challenges to comparing results across studies. Here we recorded
      heart rate, electrodermal activity (EDA), pupil size, head movement velocity and
      peripheral accelerometry concurrently while a cohort of 37 typical 12-month-old
      infants completed a mixed assessment battery lasting approximately 20 min per
      participant. We analysed covariation of these autonomic indices in three ways:
      first, tonic (baseline) arousal; second, co-variation in spontaneous (phasic)
      changes during testing; third, phasic co-variation relative to an external
      stimulus event. We found that heart rate, head velocity and peripheral
      accelerometry showed strong positive co-variation across all three analyses. EDA
      showed no co-variation in tonic activity levels but did show phasic positive co
      variation with other measures, that appeared limited to sections of high but not
      low general arousal. Tonic pupil size showed significant positive covariation,
      but phasic pupil changes were inconsistent. We conclude that: (i) there is high
      covariation between autonomic indices in infants, but that EDA may only be
      sensitive at extreme arousal levels, (ii) that tonic pupil size covaries with
      other indices, but does not show predicted patterns of phasic change and (iii)
      that motor activity appears to be a good proxy measure of ANS activity. The
      strongest patterns of covariation were observed using epoch durations of 40s per
      epoch, although significant covariation between indices was also observed using
      shorter epochs (1 and 5s).

PMID- 26316361
TI  - Anxious women do not show the expected decrease in cardiovascular stress
      responsiveness as pregnancy advances.
AB  - Altered stress responsiveness is a risk factor for mental and physical illness.
      In non-pregnant populations, it is well-known that anxiety can alter the
      physiological regulation of stress reactivity. Characterization of corresponding
      risks for pregnant women and their offspring requires greater understanding of
      how stress reactivity and recovery are influenced by pregnancy and women's
      anxiety feelings. In the current study, women were presented repeatedly with
      mental arithmetic stress tasks in the first and third pregnancy trimester and
      reported their trait anxiety using the state trait anxiety inventory.
      Cardiovascular stress reactivity in late pregnancy was lower than reactivity in
      the first pregnancy trimester (heart rate (HR): t(197)=4.98, p<.001; high
      frequency heart rate variability (HF HRV): t(196)=-2.09, p=.04). Less attenuation
      of stress reactivity occurred in more anxious women (HR: b=0.15, SE=0.06, p=.008;
      HF HRV: b=-10.97, SE=4.79, p=.02). The study design did not allow the influence
      of habituation to repeated stress task exposure to be assessed separately from
      the influence of pregnancy progression. Although this is a limitation, the clear
      differences between anxious and non-anxious pregnant women are important,
      regardless of the extent to which differing habituation between the groups is
      responsible. Less dampened stress reactivity through pregnancy may pose long-term
      risks for anxious women and their offspring. Follow-up studies are required to
      determine these risks.

PMID- 26316362
TI  - Reply to the letter: WhatsApp with patient data transmitted via instant
      messaging?

PMID- 26316363
TI  - Meta-analysis of randomized trials comparing nonpenetrating vs mechanical mesh
      fixation in laparoscopic inguinal hernia repair.
AB  - BACKGROUND: Evidence for open groin hernia repair demonstrates less pain with
      bioglue mesh fixation compared with invasive methods. This study aimed to assess
      the short- and long-term effects of laparoscopic groin hernia repair with
      noninvasive and invasive mesh fixation. DATA SOURCES: A systematic review of
      MEDLINE, CENTRAL, and OpenGrey was undertaken. Randomized trials assessing the
      outcome of laparoscopic groin hernia repair with invasive and noninvasive
      fixation methods were considered for data synthesis. Nine trials encompassing
      1,454 patients subjected to laparoscopic hernia repair with mesh fixation using
      biologic or biosynthetic glue were identified. Short-term data were inadequate
      for data synthesis. Chronic pain was less frequently reported by patients
      subjected to repair with biologic glue fixation than with penetrating methods
      (odds ratio .46, 95% confidence interval .22 to .93). Duration of surgery,
      incidence of seroma/hematoma, morbidity, and recurrence were similar.
      CONCLUSIONS: Laparoscopic groin hernia repair with bioglue mesh fixation was
      associated with a reduced incidence of chronic pain compared with mechanical
      fixation, without increasing morbidity or recurrence. Longer term data on
      recurrence are necessary.

PMID- 26316364
TI  - Alteration of forest succession and carbon cycling under elevated CO2.
AB  - Regenerating forests influence the global carbon (C) cycle, and understanding how
      climate change will affect patterns of regeneration and C storage is necessary to
      predict the rate of atmospheric carbon dioxide (CO2 ) increase in future decades.
      While experimental elevation of CO2 has revealed that young forests respond with
      increased productivity, there remains considerable uncertainty as to how the long
      term dynamics of forest regrowth are shaped by elevated CO2 (eCO2 ). Here, we use
      the mechanistic size- and age- structured Ecosystem Demography model to
      investigate the effects of CO2 enrichment on forest regeneration, using data from
      the Duke Forest Free-Air Carbon dioxide Enrichment (FACE) experiment, a forest
      chronosequence, and an eddy-covariance tower for model parameterization and
      evaluation. We find that the dynamics of forest regeneration are accelerated, and
      stands consistently hit a variety of developmental benchmarks earlier under eCO2
      . Because responses to eCO2 varied by plant functional type, successional
      pathways, and mature forest composition differed under eCO2 , with mid- and late
      successional hardwood functional types experiencing greater increases in biomass
      compared to early-successional functional types and the pine canopy. Over the
      simulation period, eCO2 led to an increase in total ecosystem C storage of 9.7 Mg
      C ha(-1) . Model predictions of mature forest biomass and ecosystem-atmosphere
      exchange of CO2 and H2 O were sensitive to assumptions about nitrogen limitation;
      both the magnitude and persistence of the ecosystem response to eCO2 were reduced
      under N limitation. In summary, our simulations demonstrate that eCO2 can result
      in a general acceleration of forest regeneration while altering the course of
      successional change and having a lasting impact on forest ecosystems. 

PMID- 26316365
TI  - Clicked Isoreticular Metal-Organic Frameworks and Their High Performance in the
      Selective Capture and Separation of Large Organic Molecules.
AB  - Three highly porous metal-organic frameworks (MOFs) with a uniform rht-type
      topological network but hierarchical pores were successfully constructed by the
      assembly of triazole-containing dendritic hexacarboxylate ligands with Zn(II)
      ions. These transparent MOF crystals present gradually increasing pore sizes upon
      extension of the length of the organic backbone, as clearly identified by
      structural analysis and gas-adsorption experiments. The inherent accessibility of
      the pores to large molecules endows these materials with unique properties for
      the uptake of large guest molecules. The visible selective adsorption of dye
      molecules makes these MOFs highly promising porous materials for pore-size
      dependent large-molecule capture and separation. 

PMID- 26316366
TI  - Solving the puzzle of posthospital recovery: What is the role of the individual
      physician?
AB  - Improving transitions of care from the acute care setting has been an important
      focus of health policy in the United States and Canada. Over the past decade,
      hospital performance metrics related to successful recovery have been used in the
      United States to implement incentives for reform. This focus has led to a
      laudable number of interventions to reduce readmissions--a proxy for failed
      recovery--but most of these have focused on the hospital or system level rather
      than the individual physician level. Individual physicians in both the inpatient
      and outpatient setting have important roles to play, but little guidance or
      structured support is available to them to enable successful engagement in
      postdischarge management of patient transitions. We describe several tensions of
      physician engagement in this process from the perspective of front-line providers
      and highlight several possible approaches to improve physician engagement in
      transitions.

PMID- 26316367
TI  - Adrenal Calcification in an Infant with Cholestasis.

PMID- 26316368
TI  - The Patent Ductus Arteriosus Problem: Infants Who Still Need Treatment.

PMID- 26316369
TI  - Pitted Keratolysis.

PMID- 26316370
TI  - Presentation of Celiac Disease in Finnish Children Is No Longer Changing: A 50
      Year Perspective.
AB  - OBJECTIVES: To chart trends in the presentation of celiac disease in a large
      cohort of Finnish children diagnosed over a period of 48 years. STUDY DESIGN:
      Clinical and serologic data, severity of small-bowel mucosal damage, and presence
      of associated conditions were gathered from 596 children diagnosed with celiac
      disease in 1966-2013. The children were divided into 4 groups based on the year
      of diagnosis (before 1980, 1980-1999, 2000-2009, and 2010-2013), and the
      variables were compared between the periods. The incidence of celiac disease
      autoimmunity in 2001-2013 was calculated based on the number of new antibody
      positive cases in each year. RESULTS: Age at diagnosis rose from median 4.3 years
      before 1980 to between 7.6 and 9.0 years in the later periods. The severity of
      clinical presentation, in general, became milder and poor growth less common
      during the entire study period of 50 years. Percentages of children with
      classical gastrointestinal presentation decreased, and those with atypical or
      subclinical presentation increased after the 1990s, these changes leveling off in
      2000-2013. Similarly, the severity of small-bowel mucosal damage was milder after
      the 1990s. The incidence of celiac disease autoimmunity increased in the early
      2000s but then fluctuated without a clear trend. There were no significant
      secular changes in sex distribution, presence of anemia, levels of celiac
      antibodies, or celiac disease-associated conditions. CONCLUSIONS: The clinical
      and histologic presentation of celiac disease in children became milder,
      especially in the 1980s and 1990s. However, most of these changes have reached a
      plateau in recent years.

PMID- 26316371
TI  - Identifying Differences in Risk Factors for Depression and Anxiety in Pediatric
      Chronic Disease: A Matched Cross-Sectional Study of Youth with Lupus/Mixed
      Connective Tissue Disease and Their Peers with Diabetes.
AB  - OBJECTIVE: To investigate differences in risk factors for depression and anxiety,
      such as central nervous system involvement in systemic lupus erythematosus
      (SLE)/mixed connective tissue disease (MCTD), by comparing youth with SLE/MCTD to
      peers with type 1 diabetes mellitus (T1D). STUDY DESIGN: We conducted a cross
      sectional study of 50 outpatient pairs, ages 8 years and above, matching subjects
      with SLE/MCTD and T1D by sex and age group. We screened for depression, suicidal
      ideation, and anxiety using the Patient Health Questionnaire-9 and the Screen for
      Childhood Anxiety Related Emotional Disorders, respectively. We collected parent
      reported mental health treatment data. We compared prevalence and treatment rates
      between subjects with SLE/MCTD and T1D, and identified disease-specific risk
      factors using logistic regression. RESULTS: Depression symptoms were present in
      23%, suicidal ideation in 15%, and anxiety in 27% of participants. Compared with
      subjects with T1D, subjects with SLE/MCTD had lower adjusted rates of depression
      and suicidal ideation, yet poorer rates of mental health treatment (24% vs 53%).
      Non-White race/ethnicity and longer disease duration were independent risk
      factors for depression and suicidal ideation. Depression was associated with poor
      disease control in both groups, and anxiety with insulin pump use in subjects
      with T1D. CONCLUSION: Depression and anxiety are high and undertreated in youth
      with SLE/MCTD and T1D. Focusing on risk factors such as race/ethnicity and
      disease duration may improve their mental health care. Further study of central
      nervous system and other disease-related factors may identify targets for
      intervention.

PMID- 26316372
TI  - External Validation of CROES Nephrolithometry as a Preoperative Predictive System
      for Percutaneous Nephrolithotomy Outcomes.
AB  - PURPOSE: We externally validated CROES (Clinical Research Office of the
      Endourological Society) nephrolithometry and evaluated the predictive accuracy of
      the nomogram. MATERIALS AND METHODS: Data were collected on patients who
      underwent percutaneous nephrolithotomy between January 2012 and February 2015.
      The CROES nomogram was applied to all patients and externally validated. The AUC
      and calibration plot were used for discrimination and clinical validity
      assessment. RESULTS: A total of 176 patients were included in study. Mean +/- SD
      patient age was 55.2 +/- 13.9 years and the mean stone burden was 640.0 +/- 911.4
      mm(2). The CROES nomogram was significantly associated with stone number,
      location and burden, and the number of implicated calyces, punctures and tracts.
      The postoperative treatment success rate was 85.8%. The number of stones, number
      of implicated calyces and CROES score were independent predictors of treatment
      success. The estimated AUC was 0.715 and the model provided good calibration.
      CONCLUSIONS: The CROES nomogram is an accurate tool to estimate renal stone
      complexity. CROES nephrolithometry provides great accuracy to predict
      postoperative efficacy.

PMID- 26316373
TI  - Postauricular conchal chondrocutaneous sandwich flap for partial ear
      reconstruction.

PMID- 26316374
TI  - The Double-Tongue Method: A new reconstruction technique for oral floor
      reconstruction after total glossectomy.

PMID- 26316375
TI  - Prognostic significance of preoperative absolute peripheral monocyte count in
      esophageal squamous cell carcinoma.
AB  - The objective of this study was to investigate the prognostic value of peripheral
      blood monocytes in esophageal squamous cell carcinoma (ESCC) patients who
      underwent esophagectomy. Records from 218 consecutive patients with
      histologically diagnosed ESCC who underwent esophagectomy at Qilu Hospital of
      Shandong University from January 2007 to December 2008 were retrospectively
      reviewed. The median disease-free survival (DFS) of this cohort was 29.0 months,
      and the 5-year DFS rate was 34.4%. The median overall survival (OS) was 35.0
      months, and the 5-year OS rate was 37.6%. The cut-off value of 0.42 * 109 /L for
      the absolute monocyte count (AMC) was chosen as optimal to discriminate between
      survival and death by applying receiver operating curve analysis. There were 131
      patients (60.1%) who had high AMC (>=0.42 * 109 /L) preoperatively. We found that
      AMC was significantly associated with gender, tumor location, and platelet count.
      Kaplan-Meier survival analysis of patients with high preoperative AMC had a
      significant worse prognosis for DFS (high vs. low: 27.5% vs. 39.0%, P = 0.015)
      and OS (high vs. low: 31.1% vs. 44.8%, P = 0.009) than those with low
      preoperative AMC. In a multivariate analysis, preoperative AMC was an independent
      prognostic factor for DFS (P = 0.025, hazard ratio [HR]: 1.469, 95% confidence
      interval [CI]: 1.050-2.054) and OS (P = 0.015, HR: 1.547, 95% CI: 1.088-2.200).
      In addition, among 140 patients without both preoperative and postoperative
      therapy, significantly worse OS (P = 0.012) and marginally reduced DFS (P =
      0.079) were found in the high AMC cohort versus the low AMC cohort. A higher
      preoperative absolute peripheral monocyte count can be considered as a useful
      prognostic marker of ESCC patients who underwent esophagectomy.

PMID- 26316376
TI  - Survey of Opioid and Barbiturate Prescriptions in Patients Attending a Tertiary
      Care Headache Center.
AB  - OBJECTIVE: To educate physicians about appropriate acute migraine treatment
      guidelines by determining (1) where headache patients were first prescribed
      opioids and barbiturates, and (2) the characteristics of the patient population
      who had been prescribed opioids and barbiturates. BACKGROUND: Several specialty
      societies issued recommendations that caution against the indiscriminate use of
      opioids or barbiturate containing medications for the treatment of migraine.
      These medications are still being prescribed in various medical settings and
      could put headache specialists in a difficult position when patients request
      these agents. METHODS: Patients presenting to a headache center comprised of
      eight physicians were asked to complete a survey that assessed headache types,
      comorbid conditions, and whether they had ever been prescribed opioids or
      barbiturates. If they responded affirmatively to the latter question, they were
      asked about the prescribing doctor, medication effectiveness, and whether they
      were currently on the medication. Data collection took place over a one month
      period. RESULTS: Two hundred forty-four patients were given the survey and 218 of
      these patients completed it. The predominant diagnosis was migraine (83.9%). More
      than half of the patients reported having been prescribed an opioid (54.8%) or a
      barbiturate (56.7%). About one fifth were on opioids (19.4%) or barbiturates
      (20.7%) at the time of completing the survey. Most patients reported being on
      opioids for more than 2 years (24.6%) or less than one week (32.1%). The reasons
      most frequently cited for stopping opioids were that the medications did not help
      (30.9%) or that they saw a new doctor who would not prescribe them (29.4%). Among
      patients who had previously been on barbiturates, 32.2% had been on these for
      over 2 years. Most patients (61.8%) stopped barbiturates because they did not
      find the medication helpful, while 17.6% said they saw a new doctor who would not
      prescribe them. The physician specialty most frequently cited as being the first
      prescriber for opioids was emergency medicine (20.2%) with family doctors and
      general neurologists the next groups at 17.7% each. General neurologists were the
      most frequent (37.8%) first prescribers of barbiturates. CONCLUSIONS:
      Approximately 20% of patients presenting to a headache center reported current
      use of opioids and/or barbiturates. ED physicians were reported to be the most
      frequent first prescribers of opioids and general neurologists were the most
      frequent first prescribers of barbiturates. Taken as a whole, these data provide
      a useful snapshot of the wide variety of physician specialties that might benefit
      from additional education on the appropriate use of opioids and barbiturate
      containing medications in patients with headaches.

PMID- 26316377
TI  - Multilevel conductance switching of a memory device induced by enhanced
      intermolecular charge transfer.
AB  - The modification of the terminal electron-donating groups induces a critical
      change in molecular aggregation and the intermolecular charge-transfer effect of
      the symmetric D-A1-A2-A1-D molecules that correlate with an addressable variation
      of memory performance from binary to ternary. 

PMID- 26316379
TI  - Non-destructive Patterning of Carbon Electrodes by Using the Direct Mode of
      Scanning Electrochemical Microscopy.
AB  - Patterning of glassy carbon surfaces grafted with a layer of nitrophenyl moieties
      was achieved by using the direct mode of scanning electrochemical microscopy
      (SECM) to locally reduce the nitro groups to hydroxylamine and amino
      functionalities. SECM and atomic force microscopy (AFM) revealed that
      potentiostatic pulses applied to the working electrode lead to local destruction
      of the glassy carbon surface, most likely caused by etchants generated at the
      positioned SECM tip used as the counter electrode. By applying galvanostatic
      pulses, and thus, limiting the current during structuring, corrosion of the
      carbon surface was substantially suppressed. After galvanostatic patterning,
      unambiguous proof of the formation of the anticipated amino moieties was possible
      by modulation of the pH value during the feedback mode of SECM imaging. This
      patterning strategy is suitable for the further bio-modification of
      microstructured surfaces. Alkaline phosphatase, as a model enzyme, was locally
      bound to the modified areas, thus showing that the technique can be used for the
      development of protein microarrays. 

PMID- 26316380
TI  - Growth condition-dependent cell surface proteome analysis of Enterococcus
      faecium.
AB  - The last 30 years Enterococcus faecium has become an important nosocomial
      pathogen in hospitals worldwide. The aim of this study was to obtain insight in
      the cell surface proteome of E. faecium when grown in laboratory and clinically
      relevant conditions. Enterococcus faecium E1162, a clinical blood stream isolate,
      was grown until mid-log phase in brain heart infusion medium (BHI) with, or
      without 0.02% bile salts, Tryptic Soy Broth with 1% glucose (TSBg) and urine, and
      its cell surface was "shaved" using immobilized trypsin. Peptides were identified
      using MS/MS. Mapping against the translated E1162 whole genome sequence
      identified 67 proteins that were differentially detected in different conditions.
      In urine, 14 proteins were significantly more and nine proteins less abundant
      relative to the other conditions. Growth in BHI-bile and TSBg, revealed four and
      six proteins, respectively, which were uniquely present in these conditions while
      two proteins were uniquely present in both conditions. Thus, proteolytic shaving
      of E. faecium cells identified differentially surface exposed proteins in
      different growth conditions. These proteins are of special interest as they
      provide more insight in the adaptive mechanisms and may serve as targets for the
      development of novel therapeutics against this multi-resistant emerging pathogen.
      All MS data have been deposited in the ProteomeXchange with identifier PXD002497
      (http://proteomecentral.proteomexchange.org/dataset/PXD002497). 

PMID- 26316381
TI  - Clonal variation in high- and low-level phenotypic and genotypic mupirocin
      resistance of MRSA isolates in south-east London.
AB  - OBJECTIVES: Both low-level mupirocin resistance (LMR) and high-level mupirocin
      resistance (HMR) have been identified. The aim of this study was to determine the
      epidemiology of LMR and HMR in MRSA isolates at five hospitals that have used
      mupirocin for targeted decolonization as part of successful institutional control
      programmes. METHODS: All MRSA identified in three microbiology laboratories
      serving five central and south-east London hospitals and surrounding communities
      between November 2011 and February 2012 were included. HMR and LMR were
      determined by disc diffusion testing. WGS was used to derive multilocus sequence
      types (MLSTs) and the presence of HMR and LMR resistance determinants. RESULTS:
      Prevalence of either HMR or LMR amongst first healthcare episode isolates from
      795 identified patients was 9.69% (95% CI 7.72-11.96); LMR was 6.29% (95% CI 4.70
      8.21) and HMR was 3.40% (95% CI 2.25-4.90). Mupirocin resistance was not
      significantly different in isolates identified from inpatients at each
      microbiology laboratory, but was more common in genotypically defined 'hospital'
      rather than 'community' isolates (OR 3.17, 95% CI 1.36-9.30, P = 0.002). LMR was
      associated with inpatient stay, previous history of MRSA and age >=65 years; HMR
      was associated with age >=65 years and residential postcode outside London. LMR
      and HMR varied by clone, with both being low in the dominant UK MRSA clone ST22
      compared with ST8, ST36 and ST239/241 for LMR and with ST8 and ST36 for HMR.
      V588F mutation and mupA carriage had high specificity (>97%) and area under the
      curve (>83%) to discriminate phenotypic mupirocin resistance, but uncertainty
      around the sensitivity point estimate was large (95% CI 52.50%-94.44%). Mutations
      in or near the mupA gene were found in eight isolates that carried mupA but were
      not HMR. CONCLUSIONS: Mupirocin resistance was identified in <10% of patients and
      varied significantly by clone, implying that changes in clonal epidemiology may
      have an important role in determining the prevalence of resistance in conjunction
      with selection due to mupirocin use.

PMID- 26316378
TI  - Fetal microchimerism and maternal health: a review and evolutionary analysis of
      cooperation and conflict beyond the womb.
AB  - The presence of fetal cells has been associated with both positive and negative
      effects on maternal health. These paradoxical effects may be due to the fact that
      maternal and offspring fitness interests are aligned in certain domains and
      conflicting in others, which may have led to the evolution of fetal microchimeric
      phenotypes that can manipulate maternal tissues. We use cooperation and conflict
      theory to generate testable predictions about domains in which fetal
      microchimerism may enhance maternal health and those in which it may be
      detrimental. This framework suggests that fetal cells may function both to
      contribute to maternal somatic maintenance (e.g. wound healing) and to manipulate
      maternal physiology to enhance resource transmission to offspring (e.g. enhancing
      milk production). In this review, we use an evolutionary framework to make
      testable predictions about the role of fetal microchimerism in lactation, thyroid
      function, autoimmune disease, cancer and maternal emotional, and psychological
      health. Also watch the Video Abstract. 

PMID- 26316382
TI  - Omitted doses as an unintended consequence of a hospital restricted antibacterial
      system: a retrospective observational study.
AB  - OBJECTIVES: The objective of this study was to determine the frequency of omitted
      doses of antibacterial agents and explore a number of risk factors, including the
      effect of a restricted antibacterial system. METHODS: Antibacterial data were
      extracted from a hospital electronic prescribing and medication administration
      system for the period 1 January to 30 April 2014. Percentage dose omission rates
      were calculated. Omission rates for the first dose of antibacterial courses were
      analysed using logistic regression to identify any correlation between first dose
      omission rates and potential risk factors, including the antibacterials'
      restriction status and whether or not they were ward stock. RESULTS: The study
      included 90 761 antibacterial doses. Of these, 6535 (7.2%) were documented as
      having been omitted; omission of 847 (0.9% of 90 761) was due to medication being
      unavailable. Non-restricted, ward stock antibacterials had the lowest frequency
      of omission, with 6.2% (271 of 4391) first doses omitted. The prevalence was
      10.4% (27 of 260) for restricted, ward-stock antibacterials (OR = 1.6, 95% CI =
      1.0-2.4, P = 0.027) and 15.5% (53 of 341) for non-restricted, non-ward stock
      antibacterials (OR = 2.7, 95% CI = 2.0-3.7, P < 0.001). Restricted, non-ward
      stock antibacterials had the highest frequency (30.7%, 71 of 231; OR = 6.2, 95%
      CI = 4.5-8.4, P < 0.001). CONCLUSIONS: Antibacterials not stocked in clinical
      areas were significantly more likely to be omitted. The prevalence of omitted
      doses increased further if the antibiotic was also restricted. To achieve safe,
      effective antimicrobial use, a balance is needed between promoting antimicrobial
      stewardship and preventing unintended omitted doses.

PMID- 26316383
TI  - Antimicrobial stewardship: the role of scientists?--author's response.

PMID- 26316384
TI  - Occurrence of high-level azithromycin-resistant Neisseria gonorrhoeae isolates in
      China.

PMID- 26316386
TI  - Role of ToxS in the proteolytic cascade of virulence regulator ToxR in Vibrio
      cholerae.
AB  - Two of the primary virulence regulators of Vibrio cholerae, ToxR and TcpP,
      function together with cognate effector proteins. ToxR undergoes regulated
      intramembrane proteolysis (RIP) during late stationary phase in response to
      nutrient limitation at alkaline pH; however, the specific function of its cognate
      ToxS remains unresolved. In this work, we found that ToxR rapidly becomes
      undetectable in a DeltatoxS mutant when cultures are exposed to either starvation
      conditions or after alkaline pH shock individually. A DeltatoxS mutant enters
      into a dormant state associated with the proteolysis of ToxR at a faster rate
      than wild-type, closely resembling a DeltatoxR mutant. Using a mutant with a
      periplasmic substitution in ToxS, we found that the proteases DegS and DegP
      function additively with VesC and a novel protease, TapA, to degrade ToxR in the
      mutant. Overall, the results shown here reveal a role for ToxS in the
      stabilization of ToxR by protecting the virulence regulator from premature
      proteolysis. 

PMID- 26316387
TI  - [Clinical evolution and nutritional status in asthmatic children and adolescents
      enrolled in Primary Health Care].
AB  - OBJECTIVE: To evaluate the clinical evolution and the association between
      nutritional status and severity of asthma in children and adolescents enrolled in
      Primary Health Care. METHODS: A retrospective cohort study of 219 asthmatic
      patients (3 to 17 years old) enrolled in primary care services (PCSs) in Embu das
      Artes (SP), from 2007 to 2011. Secondary data: gender, age, diagnosis of asthma
      severity, other atopic diseases, family history of atopy, and body mass index. To
      evaluate the clinical outcome of asthma, data were collected on number of asthma
      exacerbations, number of emergency room consultations and doses of inhaled
      corticosteroids at follow-up visits in the 6th and 12th months. The statistical
      analysis included chi-square and Kappa agreement index, with 5% set as the
      significance level. RESULTS: 50.5% of patients started wheezing before the age of
      two years, 99.5% had allergic rhinitis and 65.2% had a positive family history of
      atopy. Regarding severity, intermittent asthma was more frequent (51.6%) and, in
      relation to nutritional status, 65.8% of patients had normal weight. There was no
      association between nutritional status and asthma severity (p=0,409). After one
      year of follow-up, 25.2% of patients showed reduction in exacerbations and
      emergency room consultations, and 16.2% reduced the amount of inhaled
      corticosteroids. CONCLUSIONS: The monitoring of asthmatic patients in PCSs showed
      improvement in clinical outcome, with a decreased number of exacerbations,
      emergency room consultations and doses of inhaled corticosteroids. No association
      between nutritional status and asthma severity was observed in this study.

PMID- 26316385
TI  - Prospective pilot study of high-dose (10 mg/kg/day) liposomal amphotericin B (L
      AMB) for the initial treatment of mucormycosis.
AB  - BACKGROUND: Mucormycosis incidence is increasing and is associated with a high
      rate of mortality. Although lipid-based formulations of amphotericin B are the
      recommended first-line treatment, only one prospective trial in a limited number
      of patients has been performed to evaluate this regimen. METHODS: Patients with
      proven or probable mucormycosis were included between June 2007 and March 2011.
      Patients were scheduled to receive 10 mg/kg/day liposomal amphotericin B (L-AMB)
      monotherapy for 1 month and surgery was performed when appropriate. The primary
      outcome was response rate at week 4 or at the end of treatment (EOT) if before
      week 4, evaluated by an independent committee. ClinicalTrials.gov Identifier:
      NCT00467883. RESULTS: Forty patients were enrolled. Response was analysed in 33
      patients at week 4. Most patients had a haematological malignancy as their
      primary underlying disease (53%). Seventy-one percent of patients underwent
      therapeutic surgery. The response rate at week 4 or at EOT was 36%, with 18%
      partial responses and 18% complete responses. The response rate at week 12 was
      45%, with 13% partial responses and 32% complete responses. Overall mortality was
      38% at week 12 and 53% at week 24. Serum creatinine doubled in 16 (40%) patients
      and returned to normal levels within 12 weeks in 10/16 (63%). CONCLUSIONS: High
      dose L-AMB for mucormycosis, in combination with surgery in 71% of cases, was
      associated with an overall response rate of 36% at week 4 and 45% at week 12 and
      creatinine level doubling in 40% of patients (transient in 63%). These results
      may serve as the basis for future clinical trials.

PMID- 26316388
TI  - Patient-controlled hospital admission: A novel concept in the treatment of severe
      eating disorders.

PMID- 26316389
TI  - Brief Report: Pulmonary Function Tests: High Rate of False-Negative Results in
      the Early Detection and Screening of Scleroderma-Related Interstitial Lung
      Disease.
AB  - OBJECTIVE: Validated methods for the screening and early diagnosis of systemic
      sclerosis (SSc; scleroderma)-related interstitial lung disease (ILD) are needed.
      The aim of this study was to evaluate the performance of pulmonary function tests
      (PFTs) compared with that of high-resolution computed tomography (HRCT) of the
      chest for the detection of SSc-related ILD in clinical practice, and to identify
      predictors of lung involvement that is functionally occult but significant on
      HRCT. METHODS: Prospectively enrolled patients with SSc were assessed according
      to the European League Against Rheumatism (EULAR)/EULAR Scleroderma Trial and
      Research standards. The assessment included PFTs and HRCT. The HRCT images were
      evaluated in a blinded manner by 2 experienced radiologists. The performance
      parameters of PFTs for the diagnosis of SSc-related ILD were calculated.
      Predictors of significant ILD as determined by HRCT in patients with normal
      forced vital capacity (FVC) values were identified through logistic regression.
      RESULTS: Among the 102 patients, 64 (63.0%) showed significant ILD on HRCT, while
      only 27 (26.0%) had an FVC <80% of predicted, and 54 (53.0%) had a decrease in
      the results of at least 1 PFT. Forty (62.5%) of 64 patients with significant ILD
      on HRCT had a normal FVC value, translating into a high false-negative rate.
      Notably, 5 of 40 patients with a normal FVC value had severe, functionally occult
      lung fibrosis; in 2 of these patients, the results of all of the PFTs were within
      normal limits. Patients with normal FVC values despite evidence of fibrosis on
      HRCT more frequently had anti-Scl-70 antibodies and diffuse SSc and less
      frequently had anticentromere antibodies (ACAs) compared with patients with both
      normal FVC values and normal HRCT results. CONCLUSION: The derived evidence-based
      data reveal a high risk of missing significant SSc-related ILD when relying
      solely on PFTs. More comprehensive screening algorithms for early detection are
      warranted. In particular, additional imaging investigations for the early
      detection of SSc-related ILD should be considered in ACA-negative patients with
      normal FVC values.

PMID- 26316391
TI  - Targeted Proapoptotic Peptides Depleting Adipose Stromal Cells Inhibit Tumor
      Growth.
AB  - Progression of many cancers is associated with tumor infiltration by mesenchymal
      stromal cells (MSC). Adipose stromal cells (ASC) are MSC that serve as adipocyte
      progenitors and endothelium-supporting cells in white adipose tissue (WAT).
      Clinical and animal model studies indicate that ASC mobilized from WAT are
      recruited by tumors. Direct evidence for ASC function in tumor microenvironment
      has been lacking due to unavailability of approaches to specifically inactivate
      these cells. Here, we investigate the effects of a proteolysis-resistant targeted
      hunter-killer peptide D-WAT composed of a cyclic domain CSWKYWFGEC homing to ASC
      and of a proapoptotic domain KLAKLAK2. Using mouse bone marrow transplantation
      models, we show that D-WAT treatment specifically depletes tumor stromal and
      perivascular cells without directly killing malignant cells or tumor-infiltrating
      leukocytes. In several mouse carcinoma models, targeted ASC cytoablation reduced
      tumor vascularity and cell proliferation resulting in hemorrhaging, necrosis, and
      suppressed tumor growth. We also validated a D-WAT derivative with a proapoptotic
      domain KFAKFAK2 that was found to have an improved cytoablative activity. Our
      results for the first time demonstrate that ASC, recruited as a component of
      tumor microenvironment, support cancer progression. We propose that drugs
      targeting ASC can be developed as a combination therapy complementing
      conventional cancer treatments. 

PMID- 26316390
TI  - Functional Restoration of gp91phox-Oxidase Activity by BAC Transgenesis and Gene
      Targeting in X-linked Chronic Granulomatous Disease iPSCs.
AB  - Chronic granulomatous disease (CGD) is an inherited immunodeficiency, caused by
      the inability of neutrophils to produce functional NADPH oxidase required for
      fighting microbial infections. The X-linked form of CGD (X-CGD), which is due to
      mutations in the CYBB (gp91phox) gene, a component of NADPH oxidase, accounts for
      about two-thirds of CGD cases. We derived induced pluripotent stem cells (iPSCs)
      from X-CGD patient keratinocytes using a Flp recombinase excisable lentiviral
      reprogramming vector. For restoring gp91phox function, we applied two strategies:
      transposon-mediated bacterial artificial chromosome (BAC) transgenesis and gene
      targeting using vectors with a fixed 5' homology arm (HA) of 8 kb and 3'HA
      varying in size from 30 to 80 kb. High efficiency of homologous recombination (up
      to 22%) was observed with increased size of the 3'HA. Both, BAC transgenesis and
      gene targeting resulted in functional restoration of the gp91phox measured by an
      oxidase activity assay in X-CGD iPSCs differentiated into the myeloid lineage. In
      conclusion, we delivered an important milestone towards the use of genetically
      corrected autologous cells for the treatment of X-CGD and monogenic diseases in
      general. 

PMID- 26316392
TI  - Biolighted Nanotorch Capable of Systemic Self-Delivery and Diagnostic Imaging.
AB  - Sensitive imaging of inflammation with a background-free chemiluminescence (CL)
      signal has great potential as a clinically relevant way of early diagnosis for
      various inflammatory diseases. However, to date, its feasibility has been
      limitedly demonstrated in vivo with locally induced inflammation models by in
      situ injection of CL probes. To enable systemic disease targeting and imaging by
      intravenous administration of CL probes, hurdles need to be overcome such as weak
      CL emission, short glowing duration, or inability of long blood circulation.
      Here, we report a CL nanoprobe (BioNT) that surmounted such limitations to
      perform precise identification of inflammation by systemic self-delivery to the
      pathological tissues. This BioNT probe was engineered by physical nanointegration
      of multiple kinds of functional molecules into the ultrafine nanoreactor
      structure (~15 nm in size) that combines solid-state fluorescence-induced
      enhanced peroxalate CL and built-in machinery to control the intraparticle
      kinetics of CL reaction. Upon intravenous injection into a normal mouse, BioNT
      showed facile blood circulation and generated a self-lighted strong CL torchlight
      throughout the whole body owing to the tiny colloidal structure with an
      antifouling surface as well as high CL sensitivity toward endogenous biological
      hydrogen peroxide (H2O2). In mouse models of local and systemic inflammations,
      blood-injected BioNT visualized precise locations of inflamed tissues with dual
      selectivity (selective probe accumulation and selective CL reaction with H2O2
      overproduced by inflammation). Even a tumor model that demands a long blood
      circulation time for targeting (>3 h) could be accurately identified by
      persistent signaling from the kinetics-tailored BioNT with a 65-fold slowed CL
      decay rate. We also show that BioNT exhibits no apparent toxicity, thus holding
      potential for high-contrast diagnostic imaging. 

PMID- 26316393
TI  - Circulating Interferon-Inducible Protein IFI16 Correlates With Clinical and
      Serological Features in Rheumatoid Arthritis.
AB  - OBJECTIVE: The interferon-inducible protein 16 (IFI16) has been detected in sera
      from patients with autoimmune/inflammatory diseases, but not in healthy subjects.
      This leaking leads to loss of tolerance toward this self-protein and the
      development of autoantibodies. In this study, clinical significance of both IFI16
      protein and anti-IFI16 antibodies in rheumatoid arthritis (RA) was investigated.
      METHODS: IFI16 protein and anti-IFI16 antibody levels were assessed by enzyme
      linked immunosorbent assay in serum samples from 154 RA patients and 182 healthy
      controls, and in synovial fluid (SF) samples from 21 RA patients and 25 patients
      with osteoarthritis (OA). RESULTS: Mean serum levels for both IFI16 and anti
      IFI16 antibodies were higher in RA patients than in healthy controls, with a
      direct correlation between IFI16 concentration and anti-IFI16 antibody titer. The
      majority of RA patients with detectable circulating IFI16 protein were also
      positive for rheumatoid factor (RF)/anti-cyclic citrullinated peptide antibody
      (anti-CCP). The latter group was found to be positive for anti-IFI16 antibodies
      as well. The mean SF concentrations of both IFI16 protein and anti-IFI16
      antibodies were higher in RA patients when compared with control OA patients.
      Interestingly, the presence of circulating IFI16 protein, but not anti-IFI16
      antibodies, significantly correlated with RA-associated pulmonary disease. This
      correlation was not dependent on the presence of anti-IFI16 antibodies, sex, and
      smoking habit. CONCLUSION: Our data demonstrate that the high levels of
      circulating IFI16 in RA are more frequent in RF/anti-CCP-positive RA patients and
      significantly associated with pulmonary involvement. The relevance of circulating
      IFI16 protein as a new clinical biomarker of RA should be verified with
      additional studies.

PMID- 26316394
TI  - Dosimetric variations due to interfraction organ deformation in cervical cancer
      brachytherapy.
AB  - We quantitatively estimated dosimetric variations due to interfraction organ
      deformation in multi-fractionated high-dose-rate brachytherapy (HDRBT) for
      cervical cancer using a novel surface-based non-rigid deformable registration. As
      the number of consecutive HDRBT fractions increased, simple addition of dose
      volume histogram parameters significantly overestimated the dose, compared with
      distribution-based dose addition. 

PMID- 26316395
TI  - Comparison of the treatment outcomes of intensity-modulated radiotherapy and two
      dimensional conventional radiotherapy in nasopharyngeal carcinoma patients with
      parapharyngeal space extension.
AB  - BACKGROUND AND PURPOSE: This study investigated the contribution of intensity
      modulated radiotherapy (IMRT) to improved treatment outcome in patients with
      nasopharyngeal carcinoma (NPC) and parapharyngeal space (PPS) extension. MATERIAL
      AND METHODS: A total of 1052 cases with PPS extension were retrospectively
      reviewed, including 512 (48.7%) patients treated with two-dimensional
      conventional radiotherapy (2D-CRT) and 540 (51.3%) patients treated with IMRT.
      RESULTS: Significant differences in local relapse-free survival (LRFS) and
      overall survival (OS) (P<0.001, P<0.001, respectively), but not distant
      metastasis-free survival (DMFS; P=0.383), were observed between the 2D-CRT and
      IMRT groups in univariate analysis. The radiotherapy technique was found to be an
      independent prognostic factor for death (HR=0.674, 95% CI: 0.537-0.846, P=0.001)
      and local recurrence (HR=0.486, 95% CI: 0.324-0.727, P<0.001), but not for DMFS.
      IMRT improved local control in patients with carotid space (CS) involvement
      compared to 2D-CRT (P<0.001). LRFS was significantly different between patients
      with and without CS extension in the 2D-CRT group (P<0.001), but not in the IMRT
      group (P=0.215). CONCLUSIONS: Compared to 2D-CRT, IMRT improved LRFS in patients
      with PPS extension, especially patients with CS extension, but did not improve
      DMFS. CS extension was not statistically prognostic for local control in NPC
      patients with PPS extension.

PMID- 26316396
TI  - Quality assurance in MR image guided adaptive brachytherapy for cervical cancer:
      Final results of the EMBRACE study dummy run.
AB  - PURPOSE: Upfront quality assurance (QA) is considered essential when starting a
      multicenter clinical trial in radiotherapy. Despite the long experience gained
      for external beam radiotherapy (EBRT) trials, there are only limited audit QA
      methods for brachytherapy (BT) and none include the specific aspects of image
      guided adaptive brachytherapy (IGABT). METHODS AND MATERIALS: EMBRACE is a
      prospective multicenter trial aiming to assess the impact of (MRI)-based IGABT in
      locally advanced cervical cancer. An EMBRACE dummy run was designed to identify
      sources and magnitude of uncertainties and errors considered important for the
      evaluation of clinical, and dosimetric parameters and their relation to outcome.
      Contouring, treatment planning and dose reporting was evaluated and scored with a
      categorical scale of 1-10. Active feedback to centers was provided to improve
      protocol compliance and reporting. A second dummy run was required in case of
      major deviations (score <7) for any item. RESULTS: Overall 27/30 centers passed
      the dummy run. 16 centers had to repeat the dummy run in order to clarify major
      inconsistencies to the protocol. The most pronounced variations were related to
      contouring for both EBRT and BT. Centers with experience in IGABT (>30 cases) had
      better performance as compared to centers with limited experience. CONCLUSION:
      The comprehensive dummy run designed for the EMBRACE trial has been a feasible
      tool for QA in IGABT of cervix cancer. It should be considered for future IGABT
      trials and could serve as the basis for continuous quality checks for
      brachytherapy centers.

PMID- 26316397
TI  - Surgical Management of Skull Base Rosai-Dorfman Disease.
AB  - BACKGROUND AND IMPORTANCE: Rosai-Dorfman disease is a rare benign histiocytic
      proliferative disorder with a self-limiting clinical course. Skull base Rosai
      Dorfman disease presents with intracranial lesions that often mimic meningiomas
      and other benign skull base tumors. The disease is difficult to diagnose
      radiographically, and tissue diagnosis exposes patients to significant
      perioperative risk. Surgical resection may require a large skull base exposure
      that risks significant surgical morbidity. Aggressive surgical resection,
      although often attempted, is of unproven efficacy. Our objective was to determine
      the optimal surgical management of skull base Rosai-Dorfman disease. CASE
      DESCRIPTION: We present 2 cases of skull base Rosai-Dorfman disease: a 26-year
      old man with a middle fossa tumor and a 15-year-old teenage girl with a
      hypothalamic tumor. In addition, we reviewed 39 cases of skull base Rosai-Dorfman
      disease reported in the literature. CONCLUSIONS: Tumors commonly occur in the
      sellar/parasellar region and result in loss of vision. Regardless of extent of
      resection, the majority of patients (>78%) have subsequent tumor regression or
      stable disease. Steroids and/or radiation are effective treatments for tumor
      recurrence. Tumor biopsy followed by observation, steroids, and/or radiation may
      be the most appropriate surgical management of skull base Rosai-Dorfman disease.

PMID- 26316398
TI  - A Novel Use of Direct Platelet Application During Surgery for Clopidogrel
      Associated Intracerebral Hemorrhage.
AB  - BACKGROUND: Dual antiplatelet therapy is associated with increased rates of
      intracerebral hemorrhage, especially in the context of subarachnoid hemorrhage.
      We present a case of a spontaneous hemorrhage in a patient treated with a
      Pipeline stent for a ruptured dissecting vertebrobasilar aneurysm and the novel
      use of direct application of platelets during surgery to control bleeding. CASE
      DESCRIPTION: A 54-year-old previously healthy woman presented with an intradural
      right vertebral artery dissection with a ruptured 6-mm pseudoaneurysm. The
      patient was started on aspirin and clopidogrel and the vessel was reconstructed
      with 2 Pipeline Embolization Devices. On postbleed day number 14, she became
      obtunded with a blown right pupil; computed tomography of the head demonstrated a
      large right temporal intracerebral hematoma. The patient was taken emergently to
      the operating room for evacuation of the clot. Intraoperatively, satisfactory
      control of bleeding was not achieved despite transfusing several units of
      platelets intravenously. Ultimately, a mixture of Floseal and platelets applied
      directly to the hematoma wall allowed prompt hemostasis. At 3 months the patient
      was doing extremely well clinically and angiography demonstrated occlusion of the
      aneurysm. CONCLUSIONS: This is the first reported description of direct
      application of platelets to achieve intraoperative hemostasis. Platelets are
      activated by thrombin and collagen and the use of Floseal (a bovine-derived,
      gelatin matrix and human-derived thrombin) further potentiated the effectiveness
      of this strategy. With the increased incidence of intracerebral hemorrhage
      associated with dual antiplatelet therapy, this technique may provide a useful
      tool in the neurosurgical armamentarium.

PMID- 26316399
TI  - Aneurysm of the A1 Segment of the Anterior Cerebral Artery Associated with the
      Persistent Primitive Olfactory Artery.
AB  - BACKGROUND: The persistent primitive artery constitutes the anterior cerebral
      artery proper. When the persistent primitive artery keeps its embryologic course
      along the olfactory bulb, it is called the persistent primitive olfactory artery
      (PPOA). CASE DESCRIPTION: A 69-year-old man presented with an incidentally
      discovered unruptured aneurysm at the origin of the PPOA. The PPOA originated at
      the A1 segment of the anterior cerebral artery, coursed anteromedially along the
      olfactory tract, made a hairpin turn posterosuperior to the midline, and formed
      the callosomarginal branch of the anterior cerebral artery. The anomalous artery
      was interpreted as a PPOA (type 3). Type 3 PPOA associated with an unruptured
      aneurysm is rare. CONCLUSIONS: There is a high incidence of aneurysms associated
      with a PPOA. Follow-up studies are necessary in the present case to monitor for
      the development of another aneurysm at the hairpin bend.

PMID- 26316400
TI  - Prioritized Venous Coiling Facilitating Endovascular Treatment of Brain
      Arteriovenous Malformations with a Fistulous Component.
AB  - BACKGROUND: Brain arteriovenous malformation (AVM) with a fistulous component
      presents a treatment challenge. The presence of the fistulous component may be
      related to either a complication from endovascular treatment, perioperative
      hemorrhagic events during surgical resection, or incomplete obliteration after
      radiosurgery. CASE DESCRIPTION: From December 2010 to May 2014, 7 consecutive
      patients (3 men, 4 women, average age, 28.7 years; age range, 11 months to 67
      years) with AVMs with a high-flow fistulous component were treated at our
      institute with venous coiling before transarterial liquid embolization. One AVM
      was grade I based on the Spetzler-Martin grading system, 1 was grade II, 3 were
      grade III, and 2 were grade IV. The nidus size ranged from 1.7 to 6.0 cm. Four
      patients had pure fistulous-type lesions, and 3 had lesions of the mixed
      fistulous-plexiform type. All AVMs shared a common feature of a high-flow
      fistulous component with a large venous pouch emerging from the nidus. After
      endovascular embolization of the AVMs, 3 patients had complete occlusion, 3
      patients had near-complete occlusion, and 1 patient had significant reduction in
      volume. There was no immediate complication after embolization, but 1 patient
      experienced delayed hemorrhage 3 days after the procedure. CONCLUSIONS:
      Prioritized transarterial venous coiling is feasible for the embolization of AVMs
      with a high-flow fistulous component and the procedure had an acceptable
      complication rate.

PMID- 26316401
TI  - Recovery of reducing sugars and volatile fatty acids from cornstalk at different
      hydrothermal treatment severity.
AB  - This study focused on the degradation of cornstalk and recovery of reducing
      sugars and volatile fatty acids (VFAs) at different hydrothermal treatment
      severity (HTS) (4.17-8.28, 190-320 degrees C). The highest recovery of reducing
      sugars and VFAs reached 92.39% of aqueous products, equal to 34.79% based on dry
      biomass (HTS, 6.31). GC-MS and HPLC identified that the aqueous contained
      furfural (0.35-2.88 g/L) and 5-hydroxymethyl furfural (0-0.85 g/L) besides
      reducing sugars and VFAs. Hemicellulose and cellulose were completely degraded at
      a HTS of 5.70 and 7.60, respectively. SEM analysis showed that cornstalk was
      gradually changed from rigid and highly ordered fibrils to molten and grainy
      structure as HTS increased. FT-IR and TGA revealed the significant changes of
      organic groups for cornstalk before and after hydrothermal treatment at different
      HTS. Hydrothermal treatment might be promising for providing feedstocks suitable
      for biohythane production.

PMID- 26316402
TI  - Integral approaches to wastewater treatment plant upgrading for odor prevention:
      Activated Sludge and Oxidized Ammonium Recycling.
AB  - Traditional physical/chemical end-of-the-pipe technologies for odor abatement are
      relatively expensive and present high environmental impacts. On the other hand,
      biotechnologies have recently emerged as cost-effective and environmentally
      friendly alternatives but are still limited by their investment costs and land
      requirements. A more desirable approach to odor control is the prevention of
      odorant formation before being released to the atmosphere, but limited
      information is available beyond good design and operational practices of the
      wastewater treatment process. The present paper reviews two widely applicable and
      economic alternatives for odor control, Activated Sludge Recycling (ASR) and
      Oxidized Ammonium Recycling (OAR), by discussing their fundamentals, key
      operating parameters and experience from the available pilot and field studies.
      Both technologies present high application potential using readily available
      plant by-products with a minimum plant upgrading, and low investment and
      operating costs, contributing to the sustainability and economic efficiency of
      odor control at wastewater treatment facilities.

PMID- 26316403
TI  - Various pretreatments of lignocellulosics.
AB  - Biomass pretreatment for depolymerizing lignocellulosics to fermentable sugars
      has been studied for nearly 200 years. Researches have aimed at high sugar
      production with minimal degradation to inhibitory compounds. Chemical, physico
      chemical and biochemical conversions are the most promising technologies. This
      article reviews the advances and current trends in the pretreatment of
      lignocellulosics for a prosperous biorefinery.

PMID- 26316404
TI  - Rapid detection of B2-ST131 clonal group of extended-spectrum beta-lactamase
      producing Escherichia coli by matrix-assisted laser desorption ionization-time-of
      flight mass spectrometry: discovery of a peculiar amino acid substitution in B2
      ST131 clonal group.
AB  - One reason for the spread of extended-spectrum beta-lactamase (ESBL)-producing
      Escherichia coli worldwide is the global pandemic of the B2-ST131 clonal group.
      We searched for the specific biomarker peaks to distinguish between the B2-ST131
      clonal group and other sequence type (ST) clonal groups isolated from clinical
      specimens obtained in our hospital. Biomarker peaks at m/z 7650 in the B2-ST131
      group (sensitivity of 100% and specificity of 89.7%) and m/z 7707 in the other ST
      clonal groups showed the highest discrimination abilities. We further verified
      reproducibility against other Japanese clinical isolates obtained in another area
      of Japan. Differences between the molecular mass at the 7650m/z and 7707m/z peaks
      indicated an E34A amino acid substitution by proteomic and genomic analysis.
      Matrix-assisted laser desorption ionization-time-of-flight mass spectrometry
      rapidly and simply identified the B2-ST131 clonal group in routine examinations
      and will allow for adequate empirical therapy and the possibility to control both
      hospital infections and the global pandemic. 

PMID- 26316405
TI  - CHROMagar Acinetobacter medium for detection of carbapenemase-producing
      Acinetobacter spp. strains from spiked stools.
AB  - The recently modified CHROMagar Acinetobacter medium was evaluated for detection
      of carbapenemase-producing Acinetobacter baumannii from spiked stools. A total of
      45 Acinetobacter spp. isolates were tested. The CHROMagar Acinetobacter medium
      had a high sensitivity of 86.5% and a specificity of 75%. This medium is likely
      to be most useful for controlling outbreaks and in endemic situations. 

PMID- 26316406
TI  - Eating Disorders and Mentalization: High Reflective Functioning in Patients with
      Bulimia Nervosa.
AB  - The theory of mentalization has recently been applied in the area of eating
      disorders (Skarderud 2012). This article reports a qualitative study based on
      interviews with five women suffering from bulimia nervosa. All five scored high
      on the Reflective Functioning Scale, indicating a highly developed ability to
      mentalize. The present qualitative study, which focuses on the women's capacity
      to relate to and regulate affects, supports the finding that they are relatively
      skilled at reflecting on their own and others' thoughts and emotions. However,
      this highly developed capacity for mentalization is apparently not helping them
      regulate their emotions. This suggests that the capacity to mentalize may not be
      as closely related to the capacity to regulate affects as Fonagy et al. (2002)
      have proposed. Indeed, the concept of mentalization may be overinclusive and in
      need of stricter definition. Thus, it might be envisaged that while the ability
      to mentalize is closely related to the ability to put feelings into words (the
      opposite of alexithymia), an ability to mentalize may not necessarily entail a
      capacity to regulate affects. Finally, the study illustrates that far from all
      eating-disordered patients have problems mentalizing. 

PMID- 26316407
TI  - Time in History and in Psychoanalysis.

PMID- 26316408
TI  - A Genocide Rooted in Religion and Culture.

PMID- 26316409
TI  - A Fatal Attraction to Death: Ian Mcewan's The Comfort of Strangers.

PMID- 26316410
TI  - An Empirical Comparison of Short-Term Psychodynamic Psychotherapy Processes:
      Distinctive Process Factors Between Successful and Unsuccessful Therapeutic
      Outcome Groups.

PMID- 26316411
TI  - The Relationship Between Defense Style and Self-Esteem in a Sample of Cognitive
      Complainers.

PMID- 26316412
TI  - The Role of Attachment and Reflective Functioning in Emotion Regulation.

PMID- 26316413
TI  - Dimensions of Depression in Mexican Americans: The Role of Attachment Style.

PMID- 26316414
TI  - The Relationship Between Theoretical Orientation and Accuracy of
      Countertransference Expectations.

PMID- 26316415
TI  - Ilka Quindeau Responds to a Review.

PMID- 26316416
TI  - Rejoinder to Quindeau.

PMID- 26316417
TI  - Parallel Algorithms in Zen and Psychoanalytic Psychotherapy.

PMID- 26316418
TI  - Effects of carbohydrate dose and frequency on metabolism, gastrointestinal
      discomfort, and cross-country skiing performance.
AB  - This study investigated carbohydrate ingestion of varied doses and frequencies
      during a simulated cross-country skiing time trial. Ten men and three women (age:
      30 +/- 7 years; V  O 2 m a x : 59.6 +/- 5.7 mL/kg/min) completed four, 30-km
      classic technique roller skiing time trials on a treadmill. A 1:1 maltodextrin
      fructose carbohydrate solution was provided at high (2.4 g/min; HC) and moderate
      (1.2 g/min; MC) ingestion rates, each at high (six feeds; HF) and low (two feeds;
      LF) frequencies. In the LF trials, blood glucose was elevated following
      carbohydrate ingestion (at 4 and 19 km) but was reduced at 14 and 29 km compared
      with HF strategies (P <= 0.05). Gastrointestinal discomfort was higher in HC-LF
      compared with all other trials (P <= 0.05). Whole-body lipid oxidation was lower
      and carbohydrate oxidation was higher in LF compared with HF trials (P <= 0.05).
      While performance time was not significantly different between trials (140:11 +/-
      15:31, 140:43 +/- 17:40, 139:12 +/- 15:32 and 140:33 +/- 17:46 min:s in HC-HF, HC
      LF, MC-HF, and MC-LF, respectively; P > 0.05), it was improved with trial order
      (P < 0.001). There was no effect of order on any other variable (P > 0.05).
      Altering carbohydrate dose or frequency does not affect cross-country ski
      performance. However, low-frequency carbohydrate ingestion resulted in poorer
      maintenance of euglycemia, reduced lipid oxidation, and increased
      gastrointestinal discomfort. 

PMID- 26316419
TI  - Gene polymorphisms of interleukin-10 and transforming growth factor beta in
      allergic rhinitis.
AB  - BACKGROUND: Allergic rhinitis (AR) is a polygenic inflammatory disorder of the
      upper respiratory airway with an increasing prevalence worldwide. Interleukin-10
      (IL-10) and transforming growth factor-beta (TGF-beta), as two cytokines with
      pleiotropic effects on both innate and adaptive immunity, play important roles in
      allergic responses. Therefore, this study was performed to evaluate the
      associations of five polymorphisms of IL-10 and TGF-beta genes with AR. MATERIALS
      AND METHODS: Ninety-eight patients with AR along with 140 healthy volunteers with
      no history of AR and with the same ethnicity of the patients were recruited in
      this study. Genotyping was done for three polymorphisms in promoter region of IL
      10 gene (rs1800896, rs1800871, rs1800872), and two polymorphisms in the exonic
      region of TGF-beta1 gene (rs1982037, rs1800471) using PCR sequence-specific
      primers method. RESULTS: A allele and AA genotype in rs1800896 of IL-10 and TT
      genotype in rs1982037 in TGF-beta were significantly less frequent in the
      patients than in controls. While the C allele and the CG genotype in rs1800471 in
      TGF-beta1 were associated with a higher susceptibility to AR. C/C and T/C
      haplotypes (rs1982037, rs1800471) in TGF-beta1 gene and A/C/A, A/T/C and G/C/A
      haplotypes (rs1800896, rs1800871, rs1800872) in IL-10 gene were found with higher
      frequencies in patients than controls. Patients with CC genotype in rs1800871 in
      Il-10 had significantly lower levels of IgE. CONCLUSION: We found that certain
      genetic variants in IL-10 and TGF-beta polymorphisms were associated with
      susceptibility to AR as well as some clinical parameters in the patients with AR.

PMID- 26316420
TI  - Major allergen from Amaranthus palmeri pollen is a profilin: Isolation, partial
      characterisation and IgE recognition.
AB  - BACKGROUND: Pollens represent a rich source of proteins that are also potential
      elicitors of IgE-mediated pollen allergy. Sensitisation to panallergens could
      play an important role in diagnosis and specific immunotherapy, because these
      molecules are present in different plant pollens and plant foods and have marked
      structural similarity in different species. Profilins are one of the most common
      panallergens to be studied because they are responsible for a large number of
      sensitisations and are clearly related to cross-reactivity and co-sensitisation.
      This study aimed to isolate and characterise a new allergen of Amaranthus palmeri
      pollen and to determine its allergenicity. METHODS: A. palmeri pollen profilin
      was purified using poly-l-proline-Sepharose affinity chromatography followed by
      anion exchanger chromatography. Identification of purified protein was carried
      out by mass spectrometry. Specific IgE was estimated in sera of patients with
      positive skin prick test to A. palmeri pollen extract, by enzyme-linked
      immunosorbent assay (ELISA). PRINCIPAL FINDINGS: Purified protein appeared as a
      single band at 14 kDa in SDS-PAGE gel. Mass spectrometric analysis of the gel
      band identified two highly conserved peptides corresponding to allergenic
      profilins from pollen of other plants. Sera from about 60% of allergic patients
      have IgE that recognises the purified A. palmeri protein. CONCLUSION: A 14 kDa
      protein of A. palmeri pollen was purified and identified as allergenic profilin,
      which was recognised by sera from pollen allergic patients.

PMID- 26316421
TI  - Relationship between respiratory and food allergy and evaluation of preventive
      measures.
AB  - Food allergy and respiratory allergy are two frequently associated diseases and
      with an increasing prevalence. Several reports show the presence of respiratory
      symptoms in patients with food allergy, while certain foods may be related to the
      development or exacerbation of allergic rhinitis and asthma. The present update
      focuses on this relationship, revealing a pathogenic and clinical association
      between food and respiratory allergy. This association is even more intense when
      the food hypersensitivity is persistent or starts in the early years of life.
      Food allergy usually precedes respiratory allergy and may be a risk factor for
      allergic rhinitis and asthma, becoming a relevant clinical marker for severe
      atopic asthma. Furthermore, the presence of co-existing asthma may enhance life
      threatening symptoms occurring during a food allergic reaction. Recommendations
      for dietary restrictions during pregnancy and breastfeeding to prevent the
      development of respiratory allergy are controversial and not supported by
      consistent scientific data. Current recommendations from medical societies
      propose exclusive breastfeeding during the first four months of life, with the
      introduction of solid food in the fourth to the seventh month period of life. A
      delayed introduction of solid food after this period may increase the risk of
      developing subsequent allergic conditions. Further studies are encouraged to
      avoid unjustified recommendations involving useless dietary restrictions. 

PMID- 26316422
TI  - Epilepsy and bipolar disorder.
AB  - It is well recognized that mood disorders and epilepsy commonly co-occur. Despite
      this, our knowledge regarding the relationship between epilepsy and bipolar
      disorder is limited. Several shared features between the two disorders, such as
      their episodic nature and potential to run a chronic course, and the efficacy of
      some antiepileptic medications in the prophylaxis of both disorders, are often
      cited as evidence of possible shared underlying pathophysiology. The present
      paper aims to review the bidirectional associations between epilepsy and bipolar
      disorder, with a focus on epidemiological links, evidence for shared etiology,
      and the impact of these disorders on both the individual and wider society.
      Better recognition and understanding of these two complex disorders, along with
      an integrated clinical approach, are crucial for improved evaluation and
      management of comorbid epilepsy and mood disorders. 

PMID- 26316423
TI  - Adherence to diabetes guidelines for screening, physical activity and medication
      and onset of complications and death.
AB  - AIMS: Analyze relationships between adherence to guidelines for diabetes care -
      regular screening; physical activity; and medication - and diabetes complications
      and mortality. METHODS: Outcomes were onset of congestive heart failure (CHF),
      stroke, renal failure, moderate complications of lower extremities, lower-limb
      amputation, proliferative diabetic retinopathy (PDR), and mortality during follow
      up. Participants were persons aged 65+ in the Health and Retirement Study (HRS)
      2003 Diabetes Study and had Medicare claims in follow-up period (2004-8).
      RESULTS: Adherence to screening recommendations decreased risks of developing CHF
      (odds ratio (OR)=0.83; 95% confidence interval (CI): 0.72-0.96), stroke (OR=0.80;
      95% CI: 0.68-0.94); renal failure (OR=0. 82; 95% CI: 0.71-0.95); and death
      (OR=0.86; 95% CI: 0.74-0.99). Adherence to physical activity recommendation
      reduced risks of stroke (OR=0.64; 95% CI: 0.45-0.90), renal failure (OR=0.71; 95%
      CI: 0.52-0.97), moderate lower-extremity complications (OR=0.71; 95% CI: 0.51
      0.99), having a lower limb amputation (OR=0.31, 95% CI: 0.11-0.85), and death
      (OR=0.56, 95% CI: 0.41-0.77). Medication adherence was associated with lower
      risks of PDR (OR=0.35, 95% CI: 0.13-0.93). CONCLUSIONS: Adherence to screening,
      physical activity and medication guidelines was associated with lower risks of
      diabetes complications and death. Relative importance of adherence differed among
      outcome measures.

PMID- 26316424
TI  - Inferring Speciation Processes from Patterns of Natural Variation in Microbial
      Genomes.
AB  - Microbial species concepts have long been the focus of contentious debate, fueled
      by technological limitations to the genetic resolution of species, by the
      daunting task of investigating phenotypic variation among individual microscopic
      organisms, and by a lack of understanding of gene flow in reproductively asexual
      organisms that are prone to promiscuous horizontal gene transfer. Population
      genomics, the emerging approach of analyzing the complete genomes of a multitude
      of closely related organisms, is poised to overcome these limitations by
      providing a window into patterns of genome variation revealing the evolutionary
      processes through which species diverge. This new approach is more than just an
      extension of previous multilocus sequencing technologies, in that it provides a
      comprehensive view of interacting evolutionary processes. Here we argue that the
      application of population genomic tools in a rigorous population genetic
      framework will help to identify the processes of microbial speciation and
      ultimately lead to a general species concept based on the unique biology and
      ecology of microorganisms. 

PMID- 26316425
TI  - Spinal sigma-1 receptor activation increases the production of D-serine in
      astrocytes which contributes to the development of mechanical allodynia in a
      mouse model of neuropathic pain.
AB  - We have previously demonstrated that activation of the spinal sigma-1 receptor
      (Sig-1R) plays an important role in the development of mechanical allodynia (MA)
      via secondary activation of the N-methyl-d-aspartate (NMDA) receptor. Sig-1Rs
      have been shown to localize to astrocytes, and blockade of Sig-1Rs inhibits the
      pathologic activation of astrocytes in neuropathic mice. However, the mechanism
      by which Sig-1R activation in astrocytes modulates NMDA receptors in neurons is
      currently unknown. d-serine, synthesized from l-serine by serine racemase (Srr)
      in astrocytes, is an endogenous co-agonist for the NMDA receptor glycine site and
      can control NMDA receptor activity. Here, we investigated the role of d-serine in
      the development of MA induced by spinal Sig-1R activation in chronic constriction
      injury (CCI) mice. The production of d-serine and Srr expression were both
      significantly increased in the spinal cord dorsal horn post-CCI surgery. Srr and
      d-serine were only localized to astrocytes in the superficial dorsal horn, while
      d-serine was also localized to neurons in the deep dorsal horn. Moreover, we
      found that Srr exists in astrocytes that express Sig-1Rs. The CCI-induced
      increase in the levels of d-serine and Srr was attenuated by sustained
      intrathecal treatment with the Sig-1R antagonist, BD-1047 during the induction
      phase of neuropathic pain. In behavioral experiments, degradation of endogenous d
      serine with DAAO, or selective blockade of Srr by LSOS, effectively reduced the
      development of MA, but not thermal hyperalgesia in CCI mice. Finally, BD-1047
      administration inhibited the development of MA and this inhibition was reversed
      by intrathecal treatment with exogenous d-serine. These findings demonstrate for
      the first time that the activation of Sig-1Rs increases the expression of Srr and
      d-serine in astrocytes. The increased production of d-serine induced by CCI
      ultimately affects dorsal horn neurons that are involved in the development of MA
      in neuropathic mice. 

PMID- 26316426
TI  - How to handle missed or delayed doses of tacrolimus in renal transplant
      recipients? A pharmacokinetic investigation.
AB  - Every transplant patient will, at least occasionally, miss immunosuppressive drug
      doses or take them outside the prescribed times. This study aims at quantifying
      the impact of poor execution on tacrolimus exposure in renal transplant patients.
      Validated pharmacokinetic tools applied in clinical setting were used to simulate
      the steady-state pharmacokinetic profiles of the drug when given as the immediate
      release formulation to renal transplant patients, being CYP3A5 expressors or not,
      and who have reached either a standard or a minimized exposure. Situations of
      interruption due to a missed or delayed dose were simulated and the impact on
      drug exposure was explored. In case of a missed dose, it was observed that: (i) a
      single forgotten dose can greatly impact exposure: up to 49% decrease for
      tacrolimus trough concentration and 70% for AUC0-12 h in patients with the
      highest clearance values; (ii) patients with a minimized exposure are the most
      affected by a missed dose; and (iii) a dose of 1.5 times the usual dose may be
      recommended after a total dose oversight. Considering that intra-patient exposure
      variability is a predictive factor of poor graft outcome, these modeling results
      may serve as recommendations for patients, both preventively and in response to
      their questions.

PMID- 26316427
TI  - A talk between fat tissue, gut, pancreas and brain to control body weight.
AB  - The incidence of obesity and its related disorders are increasing at a rate of
      pandemic proportions. Understanding the mechanisms behind the maintenance of
      energy balance is fundamental in developing treatments for clinical syndromes
      including obesity and diabetes. A neural network located in the nucleus of the
      solitary tract-area postrema complex in the hindbrain and the hypothalamus in the
      forebrain has long been implicated in the control of energy balance. In the
      hypothalamus this central neuronal network consists of small populations of
      nuclei with distinct functions such as the arcuate nucleus (ARH), the
      paraventricular nuclei of the hypothalamus (PVH), the dorsomedial (DMH), the
      ventromedial (VMH) and the lateral hypothalamus (LH). These hypothalamic areas
      form interconnected neuronal circuits that respond to fluctuations in energy
      status by altering the expression of neuropeptides, leading to changes in energy
      intake and expenditure. Regulation of these hypothalamic nuclei involves the
      actions of orexigenic peptides (ie ghrelin), which act to stimulate energy intake
      and decrease energy expenditure, and anorexigenic peptides (ie. leptin and
      insulin), which act to reduce energy intake and stimulate energy expenditure.
      Here we review the role of the ARH, DMH and PVH in the control of energy
      homeostasis and how recent advances in research technologies (Cre-loxP
      technology, optogenetics and pharmacogenetics) have shed light on the role of
      these hypothalamic nuclei in the control of energy balance. Such novel findings
      include the implication of ARH POMC and AgRP neurons in the browning of white
      adipose tissue to regulate energy expenditure as well as the likely existence of
      divergent hypothalamic pathways in the DMH and PVH in the control of food intake
      and energy expenditure. 

PMID- 26316428
TI  - Synthesis of new oxadiazole, pyrazole and pyrazolin-5-one bearing 2-((4-methyl-2
      oxo-2H-chromen-7-yl)oxy)acetohydrazide analogs as potential antibacterial and
      antifungal agents.
AB  - Two series of diversely substituted phenyldiazenyl(2-(4-methyl-2-oxo-2H-chromen-7
      yloxy)acetyl)3,5-dimethyl-1H-pyrazole 11a-g and phenyldiazenyl-1-(2-(4-methyl-2
      oxo-4-chromen-7-yloxy)acetyl)-3-methyl-1H-pyrazol-5(4)H-one 12a-j were
      synthesized. All these compounds were characterized by IR, NMR, mass spectra and
      elemental analyses. The compounds were evaluated for their in vitro antibacterial
      activity against some Gram-positive bacteria, Staphylococcus aureus, Bacillus
      subtilis, Gram-negative bacteria, Escherichia coli, Pseudomonas aeruginosa,
      Salmonella typhi and screened for antifungal activity against A. niger, U.
      maydis. The compounds showed moderate to very good antibacterial activities. 

PMID- 26316430
TI  - Normative Data of Thyroid Volume-Ultrasonographic Evaluation of 422 Subjects Aged
      0-55 Years.
AB  - OBJECTIVE: To establish local normative data of thyroid volume assessed by
      ultrasonography in subjects aged 0-55 years living in Istanbul, Turkey. METHODS:
      Subjects without any known history of thyroid disease, of major surgery and/or
      chronic disease were enrolled in the study and evaluated by physical examination
      and thyroid ultrasonography. Thyroid gland and isthmus at usual location, each
      lateral lobe volume with three dimensions, ectopic thyroid tissue and
      echogenicity of the gland were assessed. RESULTS: Initially, 494 subjects were
      enrolled in the study. Subjects showing heterogeneous thyroid parenchyma (n=21)
      and/or nodule (n=51) in ultrasonography were excluded. Final analysis covered 422
      subjects (216 males, 206 females). Thyroid volume was found to significantly
      correlate with height, weight, age and body surface area (r=0.661, r=0.712,
      r=0.772 and r=0.779, respectively; p<0.0001 for all). These correlations were
      even stronger in subjects younger than 18 years (r=0.758, r=0.800, r=0.815 and
      r=0.802, respectively; p<0.0001 for all). CONCLUSION: The study provides updated
      reference norms for thyroid volume in Turkish subjects which can be used in the
      diagnosis and follow-up of patients with thyroid diseases.

PMID- 26316429
TI  - The Diagnosis and Management of Hyperinsulinaemic Hypoglycaemia.
AB  - Insulin secretion from pancreatic beta-cells is tightly regulated to keep fasting
      blood glucose concentrations within the normal range (3.5-5.5 mmol/L).
      Hyperinsulinaemic hypoglycaemia (HH) is a heterozygous condition in which insulin
      secretion becomes unregulated and its production persists despite low blood
      glucose levels. It is the most common cause of severe and persistent
      hypoglycaemia in neonates and children. The most severe and permanent forms are
      due to congenital hyperinsulinism (CHI). Recent advances in genetics have linked
      CHI to mutations in 9 genes that play a key role in regulating insulin secretion
      (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, UCP2, HNF4A and HNF1A).
      Histologically, CHI can be divided into 3 types; diffuse, focal and atypical.
      Given the biochemical nature of HH (non-ketotic), a delay in the diagnosis and
      management can result in irreversible brain damage. Therefore, it is essential to
      diagnose and treat HH promptly. Advances in molecular genetics, imaging methods
      (18F-DOPA PET-CT), medical therapy and surgical approach (laparoscopic surgery)
      have completely changed the management and improved the outcome of these
      children. This review provides an overview of the genetic and molecular
      mechanisms leading to development of HH in children. The article summarizes the
      current diagnostic methods and management strategies for the different types of
      CHI. 

PMID- 26316431
TI  - The Effects of Six-Month L-Thyroxine Treatment on Cognitive Functions and Event
      Related Brain Potentials in Children with Subclinical Hypothyroidism.
AB  - OBJECTIVE: The aim of this study was to investigate the cognitive status of
      children with subclinical hypothyroidism (SH) before and after L-thyroxine (L-T4)
      treatment using event-related potentials (ERPs) and neuropsychological tests.
      METHODS: This prospective study was conducted on a series of 20 children with
      mild SH (free T4 normal and thyroid-stimulating hormone level within 5-10 uIU/L)
      who underwent clinical and cognitive assessment before L-T4 treatment and 6
      months afterwards. The recordings of ERPs were done at the time of diagnosis and
      after 6 months of euthyroid state. Neuropsychiatric tests for attention,
      perception, close and remote memory were performed on all patients and on the
      control group which consisted of 20 healthy children of normal intelligence.
      RESULTS: While pretreatment verbal memory (VM) and verbal recall (VR) scores of
      the SH group were significantly lower than those of the control group (p=0.004
      and 0.012, respectively), no significant differences between the post-treatment
      and control groups were found in these scores after 6 months of L-T4 treatment.
      Post-treatment VM and VR scores were significantly higher than the pretreatment
      scores in the SH group (p=0.008 and p=0.0001). There were no significant
      differences between the pre-and post-treatment values of electrophysiological
      evaluation in N1, P2, P3 latencies or P3 amplitude (p>0.05), although there was a
      significant decrease in N2 latency in the post-treatment group (p=0.03).
      CONCLUSION: SH affects cognition in children and L-T4 replacement therapy leads
      to normalization of cognitive functions. Neuropsychological tests can be used as
      complementary measures in the evaluation of children with SH. Determining the
      association between ERPs and SH would contribute to the comprehensive evaluation
      of these children.

PMID- 26316432
TI  - Evaluation of Pre-Treatment and Post-Treatment S100B, Oxidant and Antioxidant
      Capacity in Children with Diabetic Ketoacidosis.
AB  - OBJECTIVE: The study aimed to evaluate the pre-treatment and post-treatment
      oxidant capacity, antioxidant capacity and S100B protein levels in cases of
      diabetic ketoacidosis (DKA). METHODS: The study included 49 pediatric patients
      diagnosed with DKA and a control group comprising 49 healthy children. Blood
      samples were obtained after confirmation of the DKA diagnosis and also after
      treatment. S100B, total oxidant (TOL) and total antioxidant levels (TAL) were
      measured and the oxidative stress index (OSI) was calculated. RESULTS: When the
      pre-treatment and post-treatment values of patients with DKA were compared with
      those of the healthy control group, the S100B level, TOL, TAL and OSI were found
      to be significantly higher in the diabetes group (p<0.001). Pre-treatment TOL and
      TAL were also significantly higher than post-treatment levels (p<0.001), while no
      statistically significant difference was found in the S100B levels or the OSI
      (p>0.05). CONCLUSION: We believe that long-term exposure to high blood glucose
      concentrations leads to an increase in TOL in patients with DKA and that the
      neurotransmitter changes that develop in response to this exposure lead to an
      increase in S100B levels, which is an indicator of neuronal damage.

PMID- 26316433
TI  - Associations of Prenatal and Perinatal Factors with Cortisol Diurnal Pattern and
      Reactivity to Stress at Preschool Age Among Children Living in Poverty.
AB  - OBJECTIVE: To examine the association of pre- and perinatal factors with diurnal
      cortisol pattern and reactivity to a stressor at preschool age among children
      living in poverty. METHODS: Preschool aged children (n=275) provided saliva
      samples 3 times per day for 3 days to assess circadian rhythmicity (intercept and
      slope reflected diurnal pattern) and during a behavioral stress elicitation
      protocol to measure reactivity (5 samples before, during and after the stressor).
      Pre- and perinatal predictors were pregnancy weight gain, pre-pregnancy body mass
      index (BMI), infant birth weight z-score and gestational age. We ran 7 linear
      regression models predicting each of the cortisol outcomes including all pre- and
      perinatal predictors and covariates simultaneously. RESULTS: Greater pregnancy
      weight gain predicted higher morning cortisol [b=0.020 (SE 0.007), p=0.003].
      Greater pregnancy weight gain also predicted higher cortisol at recovery from the
      stressor in girls only [beta=0.002 (SE 0.001), p=0.036]. There was no association
      of pre-pregnancy BMI with any cortisol outcome. Higher birth weight z-score
      predicted higher morning cortisol in the total sample [beta=0.134 (SE 0.066,
      p=0.043]. Greater gestational age predicted lower cortisol during peak stress in
      the sample who underwent cortisol reactivity testing [beta=-0.015 (SE 0.007),
      p=0.032] and in boys [beta=-0.032 (SE 0.014), p=0.027]. CONCLUSION: Pre- and
      perinatal factors are associated with cortisol patterning in offspring at
      preschool age. The implications for child health require additional studies.

PMID- 26316434
TI  - Long-Term Treatment with n-3 Polyunsaturated Fatty Acids as a Monotherapy in
      Children with Nonalcoholic Fatty Liver Disease.
AB  - OBJECTIVE: To investigate the efficacy and safety of n-3 polyunsaturated fatty
      acids (PUFA) treatment in obese children with nonalcoholic fatty liver disease
      (NAFLD). METHODS: One hundred and eight obese (body mass index (BMI) >95th
      percentile for age and sex) adolescents with NAFLD were included in the study.
      Mean age of the subjects was 13.8 +/- 3.9 years (9-17 yrs). The diagnosis of
      NAFLD was based on the presence of liver steatosis with high transaminases. The
      subjects were randomly divided into two groups. Group 1 (PUFA group, n=52)
      received a 1000 mg dose of PUFA once daily for 12 months and lifestyle
      intervention. Group 2 (placebo group, n=56) received a recommended diet plus
      placebo and lifestyle intervention for 12 months. Insulin resistance was
      evaluated by homeostasis model assessment of insulin resistance (HOMA-IR) from
      fasting samples. RESULTS: BMI, fasting insulin levels and HOMA-IR values in both
      groups decreased significantly at the end of the study. In group 1, 67.8% of the
      patients had a decrease from baseline in the prevalence of steatosis (p<0.001).
      Frequency of elevated alanine aminotransferase (ALT) levels (39.2% to 14.2%;
      p<0.01) and elevated aspartate aminotransferase (AST) levels (25% to 17.8%;
      p=0.01) decreased significantly in the PUFA group. Following a 12-month diet plus
      placebo and lifestyle intervention treatment, 40.3% (21) of the patients in the
      placebo group also showed a decrease in frequency of steatosis (p=0.04) and
      slight decreases in frequency of elevated ALT levels (38.4% to 28.8%; p=0.01) and
      AST levels (30.7% to 28.8%; p>0.05). CONCLUSION: Our results indicated that n-3
      PUFA treatment is safe and efficacious in obese children with NAFLD and can
      improve ultrasonographic findings and the elevated transaminase levels.

PMID- 26316435
TI  - Vitamin D Deficiency and Hashimoto's Thyroiditis in Children and Adolescents: a
      Critical Vitamin D Level for This Association?
AB  - OBJECTIVE: Vitamin D has been suggested to be active as an immunomodulator in
      autoimmune diseases such as Hashimoto's thyroiditis (HT). The goal of the present
      study was to investigate the vitamin D status in HT patients. METHODS: This
      prevalence case-control study was conducted on 90 patients with HT (of ages 12.32
      +/- 2.87 years) and 79 age-matched healthy controls (11.85 +/- 2.28 years). Serum
      25-hydroxyvitamin D3 [25(OH)D3] levels were measured in all 169 subjects.
      RESULTS: The prevalence of vitamin D deficiency in HT patients (64 of 90; 71.1%)
      was significantly higher than that in the control group (41 of 79; 51.9%)
      (p=0.025). Mean serum 25(OH)D3 level in the HT group was significantly lower
      compared to the control group (16.67 +/- 11.65 vs. 20.99 +/- 9.86 ng/mL,
      p=0.001). HT was observed 2.28 times more frequently in individuals with 25(OH)D3
      levels <20 ng/mL (OR: 2.28, CI: 1.21-4.3). CONCLUSION: Vitamin D deficiency is
      associated with HT in children and adolescents. Levels lower than 20 ng/mL seem
      to be critical. The mechanism for this association is not clear.

PMID- 26316436
TI  - Vitamin D Deficiency in Children and Adolescents in Bagcilar, Istanbul.
AB  - OBJECTIVE: This study aimed to evaluate the frequency of seasonal 25
      hydroxyvitamin D [25(OH)D] deficiency and insufficiency in children and
      adolescents living in Bagcilar, district of Istanbul city. METHODS: Serum vitamin
      D levels of 280 children aged 3-17 years old were measured at the end of winter
      and at the end of summer. Of the total group, vitamin D levels were re-measured
      in 198 subjects. Vitamin D deficiency was defined as a serum 25(OH)D level less
      than 15 ng/mL and insufficiency-as levels between 15 and 20 ng/mL. Patients whose
      vitamin D levels were less than 15 ng/mL at the end of winter were treated with
      2000 units/day of vitamin D for 3 months. RESULTS: In the "end of winter"
      samples, 25(OH)D deficiency was present in 80.36% of the subjects and
      insufficiency in 11.79%. In the "end of summer" samples, vitamin D deficiency was
      detected in 3.44% and insufficiency in 27.75%. Vitamin D levels in the "end of
      winter" samples were not significantly different between boys and girls, while
      "end of summer" levels were significantly lower in girls (p=0.015). Sunlight
      exposure was significantly higher in boys (p=0.011). The group with sufficient
      dairy product consumption had significantly higher vitamin D levels in both "end
      of summer" and "end of winter" samples. Limb pain was frequently reported in
      children with low vitamin D levels in the "end of winter" samples (p=0.001).
      Negative correlations were observed between vitamin D levels and season and also
      between vitamin D levels and age. CONCLUSION: It is essential to provide
      supplemental vitamin D to children and adolescents to overcome the deficiency
      seen especially at the end of winter.

PMID- 26316437
TI  - The First Turkish Case of Hypoparathyroidism, Deafness and Renal Dysplasia (HDR)
      Syndrome.
AB  - Hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome is an autosomal
      dominant genetic disorder characterized by hypoparathyroidism, sensorineural
      deafness and renal dysplasia. We herein present the first Turkish patient with
      HDR syndrome, who has a p.R367X mutation. This report indicates that p.R367X is
      not a mutation specific for the Far Eastern populations and also that urological
      findings in infants with hypoparathyroidism should be carefully examined because
      clinical findings relating to the p.R367X mutation may show a variable age of
      onset. 

PMID- 26316438
TI  - A Deep Intronic HADH Splicing Mutation (c.636+471G>T) in a Congenital
      Hyperinsulinemic Hypoglycemia Case: Long Term Clinical Course.
AB  - Unlike other congenital fatty acid oxidation defects, short-chain L-3-hydroxyacyl
      CoA (SCHAD, HADH) deficiency is characterised by hypoglycemia with
      hyperinsulinism in the neonatal or infancy periods. The long-term and detailed
      clinical progression of the disease is largely unknown with almost 40 patients
      reported and only a few patients described clinically. We present clinical and
      laboratory findings together with the long-term clinical course of a case with a
      deep intronic HADH splicing mutation (c.636+471G>T) causing neonatal-onset
      hyperinsulinemic hypoglycemia with mild progression. 

PMID- 26316439
TI  - A Case of Subclinical Hypothyroidism with Lingual and Right Pretracheal Ectopic
      Thyroid.
AB  - Ectopic thyroid tissue is most commonly located in a single location, this being
      the lingual area. Presentation with two ectopic thyroid foci is quite unusual. A
      girl patient aged 7 years who presented with complaints of two masses in the
      right anterior neck and submandibular area is reported. Her growth pattern and
      development were normal. The masses were detected to be dual ectopic thyroid
      glands by ultrasonography, computed tomography and 99m-technetium pertechnetate
      thyroid scan. The patient also had subclinical hypothyroidism. She was treated
      with oral levothyroxine and the masses slightly decreased in size. The repeated
      thyroid function tests were within the normal limits. Thyroid function tests and
      imaging studies need to be conducted in all patients with anterior neck masses. 

PMID- 26316440
TI  - Nifedipine in Congenital Hyperinsulinism - A Case Report.
AB  - Congenital hyperinsulinism (CHI) is the commonest cause of persistent
      hypoglycemia in neonates. Diazoxide is the first-line drug in its treatment, but
      the more severe cases are usually diazoxide-resistant. Recessive ABCC8 and KCNJ11
      mutations are responsible for most (82%) of the severe diazoxide-unresponsive
      CHI. Oral nifedipine has been effective in isolated cases of CHI. Successful
      treatment of diazoxide-unresponsive CHI with a combination of octreotide and
      nifedipine has been reported in a single isolated case so far. We report here a
      case of diazoxide-resistant CHI due to homozygous ABCC8 nonsense mutation. In
      this case, hypoglycaemia uncontrolled by pancreatectomy and octreotide alone
      showed a good response to a combination of nifedipine and octreotide. Octreotide
      was tapered off by one year age and thereafter the child is euglycaemic on oral
      nifedipine alone. Continuous glucose monitoring sensor was used as an aid to
      monitor glycaemic control and was found to be a safe and reliable option reducing
      the number of needle-pricks in small children. 

PMID- 26316441
TI  - Dermal and Ophthalmic Findings in Pseudohypoaldosteronism.
AB  - Pseudohypoaldosteronism (PHA) is defined as a state of resistance to aldosterone,
      a hormone crucial for electrolyte equilibrium. The genetically transmitted type
      of PHA is primary hypoaldosteronism. Secondary hypoaldosteronism develops as a
      result of hydronephrosis or hydroureter. PHA patients suffer from severe
      hyponatremia and a severe clinical condition due to severe loss of salt can be
      encountered in the neonatal period. Dermal findings in the form of miliaria rubra
      can also develop in these patients. With the loss of salt, abnormal accumulation
      of sebum in the eye due to a defect in the sodium channels can also occur. In
      this paper, a case of PHA in a newborn showing typical dermatological and
      ophthalmological findings is presented. 

PMID- 26316442
TI  - An Unusual Presentation of 46,XY Pure Gonadal Dysgenesis: Spontaneous Breast
      Development and Menstruation.
AB  - 46,XY pure gonadal dysgenesis (Swyer syndrome) is characterized by normal female
      genitalia at birth. It usually first becomes apparent in adolescence with delayed
      puberty and amenorrhea. Rarely, patients can present with spontaneous breast
      development and/or menstruation. A fifteen-year-old girl presented to our clinic
      with the complaint of primary amenorrhea. On physical examination, her external
      genitals were completely female. Breast development and pubic hair were
      compatible with Tanner stage V. Hormonal evaluation revealed a hypergonadotropic
      state despite a normal estrogen level. Chromosome analysis revealed a 46,XY
      karyotype. Pelvic ultrasonography showed small gonads and a normal sized uterus
      for age. SRY gene expression was confirmed by multiplex polymerase chain
      reaction. Direct sequencing on genomic DNA did not reveal a mutation in the SRY,
      SF1 and WT1 genes. After the diagnosis of Swyer syndrome was made, the patient
      started to have spontaneous menstrual cycles and therefore failed to attend her
      follow-up visits. After nine months, the patient underwent diagnostic
      laparoscopy. Frozen examination of multiple biopsies from gonad tissues revealed
      gonadoblastoma. With this report, we emphasize the importance of performing
      karyotype analysis, which is diagnostic for Swyer syndrome, in all cases with
      primary or secondary amenorrhea even in the presence of normal breast
      development. We also suggest that normal pubertal development in patients with
      Swyer syndrome may be associated with the presence of a hormonally active tumor. 

PMID- 26316443
TI  - Infusion of esmolol attenuates lipopolysaccharide-induced myocardial dysfunction.
AB  - BACKGROUND: Myocardial depression, as a well-recognized manifestation of cardiac
      dysfunction, often accompanies severe sepsis and septic shock. Inflammation
      induced myocardial apoptosis is key to the development of sepsis-induced cardiac
      dysfunction. Increasing evidence suggests the anti-inflammatory role of beta1
      adrenergic blocker, esmolol, during lethal endotoxemia. However, the direct
      protective effect of esmolol on cardiomyocyte viability during sepsis is still
      not clear. Here, we aimed to study whether infusion of esmolol can directly
      inhibit myocardial apoptosis during lipopolysaccharide (LPS)-triggered
      inflammatory insult. METHODS: C57BL/6 mice were randomized into four groups as
      follows: control; esmolol infusion; LPS insult; and esmolol infusion + LPS
      insult. Function of left ventricle was assessed by invasive hemodynamics at 6 h
      after LPS insult. Terminal deoxynucleotidyl transferase mediated dUTP nick end
      labeling (TUNEL) staining, caspase-3 expression level, and the Bcl-2/Bax ratio
      were used to evaluate myocardial apoptosis at 6 h after LPS insult or esmolol
      infusion. RESULTS: Administration of LPS resulted in significant decrease in left
      ventricular end-systolic pressure, reduced maximal rate of change of left
      ventricular pressure, and the increase in left ventricular end-diastolic
      pressure. Esmolol infusion reversed LPS-induced impairment of cardiac function
      and reduced LPS-induced myocardial apoptosis that is associated with c-Jun N
      terminal kinase (JNK) and p38 activation. CONCLUSIONS: These data demonstrate
      that cardioprotection provided by esmolol infusion during LPS insult is
      associated with antiapoptotic effects and regulation of JNK and p38 activations.

PMID- 26316444
TI  - Plasma glutathione reductase activity and prognosis of septic shock.
AB  - BACKGROUND: Our aim was to investigate whether plasma glutathione reductase (GR)
      activity is well correlated with the erythrocyte-reduced glutathione
      (GSH)/glutathione disulfide (GSSG) ratio and is associated with the mortality of
      septic shock. MATERIALS AND METHODS: This study was conducted on male Sprague
      Dawley rats and patients admitted to the intensive care unit with septic shock.
      To induce endotoxemia in rats, vehicle or lipopolysaccharide (LPS) at dosages of
      5 or 10 mg/kg were injected into a tail vein. Animals were then euthanized 6 h
      post-LPS. Based on the 28-d mortality, the enrolled patients were divided into
      the survivors and nonsurvivors. We obtained blood samples from patients at
      admission (0 h) and 24 h after admission to the intensive care unit. RESULTS: In
      endotoxemic rats, the erythrocyte GSH/GSSG ratio, erythrocyte GR activity, and
      plasma GR activity in the 10 mg/kg of LPS group were lower than those in the sham
      and 5 mg/kg of LPS groups. In patients with septic shock, decrease in plasma GR
      activity at 24 h was independently associated with an increase in 28-d mortality
      (odds ratio, 0.828; 95% confidence interval, 0.690-0.992, P = 0.041). Plasma GR
      activity was correlated with erythrocyte GR activity (Spearman rho = 0.549, P <
      0.001) and the erythrocyte GSH/GSSG ratio (rho = 0.367, P = 0.009) at 24 h.
      CONCLUSIONS: Plasma GR activity was well correlated with erythrocyte GR activity
      and the erythrocyte GSH/GSSG ratio, and a decrease in plasma GR activity was
      associated with an increase in the mortality of septic shock patients.

PMID- 26316446
TI  - Ebselen induces mitochondrial permeability transition because of its interaction
      with adenine nucleotide translocase.
AB  - AIMS: Mitochondrial permeability transition is a process established through
      massive Ca(2+) load in addition to an inducer reagent. Ebselen (Ebs), an
      antioxidant seleno compound, has been introduced as a reagent which inhibits
      mitochondrial dysfunction induced by permeability transition. Paradoxically
      enough, it has been shown that Ebs may also be able to induce the opening of the
      mitochondrial non-selective pores. This study was performed with the purpose of
      establishing the membrane system involved in Ebs-induced pore opening. MAIN
      METHODS: Permeability transition was appraised by analyzing the following: i)
      matrix Ca(2+) release, and mitochondrial swelling, ii) efflux of cytochrome c,
      and iii) the inhibition of superoxide dismutase. All of these adverse reactions
      were inhibited by N-ethylmaleimide and cyclosporin A. KEY FINDINGS: At
      concentrations from 5 to 20 MUM, we found that Ebs induces non-specific membrane
      permeability. Remarkably, Ebs blocks the binding of the fluorescent reagent eosin
      5-maleimide to the thiol groups of the adenine nucleotide translocase.
      SIGNIFICANCE: Based on the above, it is tempting to hypothesize that Ebs induces
      pore opening through its binding to the ADP/ATP carrier.

PMID- 26316445
TI  - Remote ischemic conditioning temporarily improves antioxidant defense.
AB  - BACKGROUND: Remote ischemic conditioning (RIC) is the most promising surgical
      approach to mitigate ischemia and reperfusion (IR) injury. It consists in
      performing brief cycles of IR in tissues other than those exposed to ischemia.
      The underlying mechanisms of the induced protection are barely understood, so we
      evaluated if RIC works enhancing the antioxidant defense of the liver and kidney
      before IR injury. MATERIALS AND METHODS: Twenty-one Wistar rats were assigned
      into three groups as follows: sham, same surgical procedure as in the remaining
      groups was performed, but no RIC was carried out. RIC 10, RIC was performed, and
      no abdominal organ ischemia was induced. After 10 min of the end of the RIC
      protocol, the liver and kidney were harvested. RIC 60, similar procedure as
      performed in RIC 10, but the liver and the kidney were harvested 60 min. RIC
      consisted of three cycles of 5-min left hind limb ischemia followed by 5-min left
      hind limb perfusion, lasting 30 min in total. Samples were used to measure tissue
      total antioxidant capacity. RESULTS: RIC protocol increased both liver (1.064 +/-
      0.26 mM/L) and kidney (1.310 +/- 0.17 mM/L) antioxidant capacity after 10 min
      when compared with sham (liver, 0.759 +/- 0.10 mM/L and kidney, 1.08 +/- 0.15
      mM/L). Sixty minutes after the RIC protocol, no enhancement on liver (0.687 +/-
      0.13 mM/L) or kidney (1.09 +/- 0.15 mM/L) antioxidant capacity was detected.
      CONCLUSIONS: RIC works through temporary and short-term enhancement of liver and
      kidney cells antioxidant defenses to avoid the deleterious consequences of a
      future IR injury.

PMID- 26316447
TI  - Investigation of lactate calcium salt-induced beta-catenin destabilization in
      colorectal cancer cells.
AB  - AIMS: Calcium supplements appear to reduce the risk of developing colorectal
      cancer (CRC), and it is necessary to clarify the mechanisms by which they exert
      their effects. In the present study, we investigate the supplementation effect of
      calcium via lactate calcium salt (CaLa) on CRC cells, focusing on beta-catenin
      destabilization. MAIN METHODS: The clonogenic assay was performed using different
      doses of CaLa. The expression level of c-Myc and Cyclin D1 was measured in
      addition to the confirmation of beta-catenin expression in the CRC cells.
      Glycogen synthase kinase (GSK)-3beta expression was also confirmed in order to
      investigate the mechanism of beta-catenin degradation. Tumorigenic ability was
      confirmed using a xenograft animal model. KEY FINDINGS: The number of colonies
      was significantly decreased after 2.5mM CaLa treatment. CaLa-treated CRC cells
      showed a decrease in the beta-catenin expression. The quantitative level of the
      beta-catenin protein was significantly decreased in the CRC cell lysates, hence
      the expression level of c-Myc and cyclin D1 was significantly decreased following
      2.5mM CaLa treatment. We also confirmed that an increased expression of GSK-3beta
      by CaLa is a key pathway in beta-catenin degradation. In the xenograft study,
      tumorigenicity was significantly inhibited to a maximum of 45% in the CaLa
      treated group as compared with the control. SIGNIFICANCE: These results support
      the idea that calcium supplementation via CaLa contributes to beta-catenin
      degradation and is hypothesized to reduce the risk of CRC. In addition, it
      indicates the possibility of CaLa being a potential incorporating agent with
      existing therapeutics against CRC.

PMID- 26316448
TI  - The developmental toxicity and apoptosis in zebrafish eyes induced by carbon-ion
      irradiation.
AB  - AIMS: Heavy ions have become potentially radiotherapeutic tools. However, studies
      of the effects on development of normal organs were limited. Using a zebrafish
      model, this study investigated the potential developmental toxicity and cell
      apoptosis rates in eyes exposed to carbon-ion irradiation. MAIN METHODS:
      Zebrafish embryos at 12h post-fertilization (hpf) were irradiated using (12)C(6+)
      ion beams at doses of 2, 4, and 8 Gy. The reactive oxygen species (ROS)
      concentration was detected using the dichlorofluorescein-diacetate at 24, 48, and
      72 hpf. Apoptosis was assessed by acridine orange staining at 24, 48, and 72 hpf
      and was also detected using the terminal deoxynucleotidyl transferase (TdT)
      mediated dUTP nick end labeling assay, at 72 hpf. The expression of genes
      governing apoptosis was examined using real-time polymerase chain reaction at 24
      hpf. Eye size was measured at 144 hpf. KEY FINDINGS: Ion irradiation with
      (12)C(6+) induced a significant increase in cell apoptosis at 24, 48 and 72 hpf.
      However, there was no significant increase in the ROS concentration at 24, 48,
      and 72 hpf. The proapoptotic genes, including P53, Bax, and Puma, were
      significantly upregulated. Two antiapoptotic genes, Mdm2 and Bcl-2, were
      significantly downregulated, and the expression levels of Capspase-9 and Caspase
      3 were significantly increased. Microphthalmia was noted in the 8 Gy irradiated
      group. SIGNIFICANCE: These results suggested that carbon-ion irradiation induced
      apoptosis through the p53 pathway in zebrafish eyes independent of ROS
      generation. Irradiation at high doses may disrupt eye development of zebrafish
      embryos.

PMID- 26316449
TI  - Exercise training and taurine supplementation reduce oxidative stress and prevent
      endothelium dysfunction in rats fed a highly palatable diet.

PMID- 26316450
TI  - Adrenomedullin induces pulmonary vasodilation but does not attenuate pulmonary
      hypertension in a sheep model of acute pulmonary embolism.
AB  - AIMS: The pulmonary vasodilation induced by adrenomedullin may be beneficial in
      the acute pulmonary embolism (APE) setting. This study examined effects of
      adrenomedullin in sheep with microsphere-induced APE. MAIN METHODS: Twenty four
      anesthetized, mechanically ventilated sheep were randomly assigned into 3 groups
      (n=8 per group): animals not subjected to any intervention (Sham), animals with
      APE induced by microspheres (500 mg, intravenously) treated 30 min later by
      intravenous physiological saline (Emb group) or intravenous adrenomedullin (50
      ng/kg/min) during 30 min (Emb+Adm group). Plasma concentrations of cyclic
      adenosine (cAMP) and guanosine monophosphate (cGMP) were determined by enzyme
      immunoassay. KEY FINDINGS: Variables did not change over time in sham animals. In
      both embolized groups, microsphere injection significantly (P<0.05) increased
      pulmonary vascular resistance index (PVRI) and mean pulmonary artery pressure
      (MPAP) from baseline by 181% and 111-142%, respectively (% change in mean
      values). Adrenomedullin significantly decreased PVRI (18%-25%) and significantly
      increased cardiac index (22%-25%) from values recorded 30 min after APE (E30),
      without modifying MPAP. Adrenomedullin decreased mean arterial pressure (18%-24%)
      and systemic vascular resistance index (32%-40%). Embolization significantly
      increased arterial-to-end tidal CO2 gradient, alveolar-to-arterial O2 gradient,
      and pulmonary shunt fraction from baseline, but these variables were unaffected
      by adrenomedullin. While adrenomedullin significantly increased plasma cAMP, cGMP
      levels were unaltered. SIGNIFICANCE: Adrenomedullin induces systemic and
      pulmonary vasodilation, possibly via a cAMP mediated mechanism, without modifying
      the gas exchange impairment associated with APE. The pulmonary anti-hypertensive
      effect of adrenomedullin may be offset by increases in cardiac index.

PMID- 26316452
TI  - Finishing procedures in orthodontic-surgical cases.
AB  - To ensure optimal results, we must do our utmost to achieve targets based on
      order, symmetry and precision, our ultimate aim being to strive towards the
      desired harmony, planned contrast and exact proportions. Orthodontic-surgical
      treatments require specific finishing procedures, which most often call for
      multidisciplinary, or even transdisciplinary, collaboration. Finishing will
      involve the dental arches just as much as the orofacial environment. Above all,
      treatment of this kind demands a highly targeted approach in combination with
      well-defined and perfectly executed techniques. To finish a case satisfactorily,
      reasonable targets should be aimed for to ensure they are achieved. One must be
      ambitious and yet wise. A tight alliance of surgeon and orthodontist will nurture
      convincing and achievable projects and good, lifelong outcomes. Following the
      consolidation phase, roughly 4 to 6 weeks post-surgery, we can initiate the final
      orthodontic treatment, which, in effect, constitutes a mini-treatment in its own
      right. "Details make perfection, but perfection is not a detail" (Leonardo Da
      Vinci). "A lucid mind is the ante-chamber of intelligence" (Leo Ferre). In the
      order of life, every form of unity is always unique, and if each of us is unique,
      it is because everyone else is too. Ambition, wisdom, lucidity and efficiency
      will guarantee a successful result, the successful result. We must not be mere
      observers of our treatments, but the architect, project manager and site foreman
      at one and the same time. One could talk ad infinitum about finishing orthodontic
      surgical cases because everything else leads up to the case-finishing and even
      the fullest description could never be exhaustive.

PMID- 26316454
TI  - Actin shapes the autophagosome.
AB  - Compared with most intracellular vesicles, the autophagosome is formed by an
      unusual event of vesicle budding involving an elusive sequence of membrane
      expansions that ends with a double membrane vesicle. It is now shown that actin
      polymerization inside the forming autophagosome is a driving force for the
      expansion and assembly of a functional autophagosome. 

PMID- 26316453
TI  - Microtubule nucleation at the centrosome and beyond.

PMID- 26316455
TI  - Fumarate in DNA repair.
AB  - A new study suggests that fumarase, a metabolic enzyme normally associated with
      ATP production in mitochondria, is recruited to sites of DNA damage where it
      produces fumarate to inhibit histone demethylation and promote repair of DNA
      double strand breaks. 

PMID- 26316456
TI  - Corrigendum: The oncogene c-Jun impedes somatic cell reprogramming.

PMID- 26316457
TI  - Single-shot analytical assay based on graphene-oxide-modified surface acoustic
      wave biosensor for detection of single-nucleotide polymorphisms.
AB  - The combination of a surface acoustic wave (SAW) biosensor with graphene oxide
      (GO) provides a promising perspective for detecting DNA mutation. The GO-modified
      SAW biosensor was prepared by conjugating GO onto the SAW chip surface via
      electrostatic interaction. Afterward, the probe was immobilized on the GO
      surface, and detection of DNA mutation was realized by hybridization. The
      hybridization with a variety of targets would yield different mass and
      conformational changes on the chip surface, causing the different SAW signals in
      real time. A total of 137 clinical samples were detected by a single-shot
      analytical assay based on GO-modified SAW biosensor and direct sequencing in
      parallel. The diagnostic performance (both sensitivity and specificity) of the
      assay was evaluated with the direct sequencing as a reference testing method. The
      phase-shift value of three genotypes in 137 clinical samples was significantly
      different (p < 0.001). Furthermore, testing of diagnostic performance yielded
      diagnostic sensitivity and specificity of 100% and 88.6% for identifying CT and
      CC genotype, 98.0% and 96.2% for identifying CT and TT genotype, respectively.
      The single-shot analytical assay based on the GO-modified SAW biosensor could be
      exploited as a potential useful tool to identify CYP2D6*10 polymorphisms in
      clinical practice of personalized medicine. 

PMID- 26316458
TI  - Data integration of structured and unstructured sources for assigning clinical
      codes to patient stays.
AB  - OBJECTIVE: Enormous amounts of healthcare data are becoming increasingly
      accessible through the large-scale adoption of electronic health records. In this
      work, structured and unstructured (textual) data are combined to assign clinical
      diagnostic and procedural codes (specifically ICD-9-CM) to patient stays. We
      investigate whether integrating these heterogeneous data types improves
      prediction strength compared to using the data types in isolation. METHODS: Two
      separate data integration approaches were evaluated. Early data integration
      combines features of several sources within a single model, and late data
      integration learns a separate model per data source and combines these
      predictions with a meta-learner. This is evaluated on data sources and clinical
      codes from a broad set of medical specialties. RESULTS: When compared with the
      best individual prediction source, late data integration leads to improvements in
      predictive power (eg, overall F-measure increased from 30.6% to 38.3% for
      International Classification of Diseases, Ninth Revision, Clinical Modification
      (ICD-9-CM) diagnostic codes), while early data integration is less consistent.
      The predictive strength strongly differs between medical specialties, both for
      ICD-9-CM diagnostic and procedural codes. DISCUSSION: Structured data provides
      complementary information to unstructured data (and vice versa) for predicting
      ICD-9-CM codes. This can be captured most effectively by the proposed late data
      integration approach. CONCLUSIONS: We demonstrated that models using multiple
      electronic health record data sources systematically outperform models using data
      sources in isolation in the task of predicting ICD-9-CM codes over a broad range
      of medical specialties.

PMID- 26316459
TI  - Extremely rare borderline phyllodes tumor in the male breast: a case report.
AB  - Phyllodes tumor of the male breast is an extremely rare disease, and far fewer
      cases of borderline phyllodes tumors than benign or malignant tumors in the male
      breast have been reported. We report a case of borderline phyllodes tumor in the
      male breast with imaging findings of the tumor and pathologic correlation. 

PMID- 26316460
TI  - Interpretation of bedside chest X-rays in the ICU: is the radiologist still
      needed?
AB  - PURPOSE: To compare diagnostic accuracy of intensivists to radiologists in
      reading bedside chest X-rays. METHODS: In a retrospective trial, 33 bedside chest
      X-rays were evaluated by five radiologists and five intensivists with different
      experience. Images were evaluated for devices and lung pathologies. Interobserver
      agreement and diagnostic accuracy were calculated. Computed tomography served as
      reference standard. RESULTS: Seniors had higher diagnostic accuracy than
      residents (mean-ExpB(Senior)=1.456; mean-ExpB(Resident)=1.635). Interobserver
      agreement for installations was more homogenously distributed between
      radiologists compared to intensivists (ExpB(Rad)=1.204-1.672; ExpB(Int)=1.005
      2.368). Seniors had comparable diagnostic accuracy. CONCLUSION: No significant
      difference in diagnostic performance was seen between seniors of both
      disciplines, whereas the resident intensivists might still benefit from an
      interdisciplinary dialogue.

PMID- 26316461
TI  - Ten Years of a National Oral Health Policy in Brazil: Innovation, Boldness, and
      Numerous Challenges.
AB  - Brazil is the only country in the world to propose a universal health care system
      with the aim of guaranteeing delivery of all levels of health care, free of
      charge, to a population of over 200 million inhabitants by means of a unified
      health system ("Sistema Unico de Saude" [SUS]). The national policy of oral
      health, also known as Smiling Brazil ("Brasil Sorridente"), was implemented in
      2004. Oral health was designated as 1 of the 4 priority areas of the SUS,
      transforming oral health care in Brazil, with the objective that the SUS achieve
      the integrality of care envisaged at its creation. The aim of this article is to
      share part of this experience in order to prompt reflection about the inclusion
      of oral health care in other health care systems around the world. The most
      significant results of Smiling Brazil can be seen in 3 areas: (1) oral health
      epidemiological indicators, (2) financial investment and professional
      development, and (3) the building of an oral health care network throughout the
      10 y of the policy. The "Discovery!" article presented here portrays 10 y of
      evolution; however, it is important to point out that this is a process
      undergoing construction and that the oral health care network needs to be further
      expanded, refined, and solidified so that over time and through changes in the
      political parties in power, Smiling Brazil prevails as a perennial policy and not
      merely an action by a single government.

PMID- 26316462
TI  - Response to Letter to the Editor, "Multiscale Analyses of the Bone-implant
      Interface".

PMID- 26316463
TI  - Letter to the Editor, "Multiscale Analyses of the Bone-implant Interface".

PMID- 26316464
TI  - Efficient cleavage of DNA oligonucleotides by a non-FokI-type zinc finger
      nuclease containing one His4-type finger domain derived from the first finger
      domain of Sp1.
AB  - In this study, we sought to improve the hydrolytic activity of a His4-type single
      finger domain (f2), which was previously derived from the second finger domain
      (f2') of the Sp1 zinc finger protein (Sp1wt), which has 3 tandem finger domains
      (f1', f2', and f3'). To this end, 2 His4-type single finger domains were
      generated by mutating 2 Cys residues participating in Zn(II) coordination with
      the His residues in the first (f1') and third finger (f3') domains of Sp1wt.
      Circular dichroism spectroscopy results showed that the first and second His4
      type zinc finger domains (f1 and f2) adopted folded betabetaalpha structures in
      the presence of Zn(II), but that the third His4-type zinc finger domain (f3) did
      not. Non-FokI-type zinc finger nucleases containing 3 or 4 finger domains were
      also prepared by combining a His4-type zinc finger domain with the Sp1wt
      scaffold. We studied their DNA-binding abilities and hydrolytic activities
      against DNA oligonucleotides by performing gel-mobility-shift assays. The results
      showed that f1 had higher hydrolytic activity for a DNA oligonucleotide with a GC
      box (5'-GGG GCG GGG-3'), compared with that of f2, although both His4-type single
      finger domains had similar DNA-binding affinities. The difference in the
      hydrolytic activity between f1 and f2 was ascribed not only to the zinc
      coordinate structure, but also to its folding structure and the stability of
      finger domain. 

PMID- 26316465
TI  - Thiophene-expanded guanosine analogues of Gemcitabine.
AB  - The chemotherapeutic drug Gemcitabine, 2',2'-difluoro-2'-deoxycytidine, has long
      been the standard of care for a number of cancers. Gemcitabine's chemotherapeutic
      properties stem from its 2',2'-difluoro-2'-deoxyribose sugar, which mimics the
      natural nucleoside, but also disrupts nucleic acid synthesis, leading to cell
      death. As a result, numerous analogues have been prepared to further explore the
      biological implications for this structural modification. In that regard, a
      thieno-expanded guanosine analogue was of interest due to biological activity
      previously observed for the tricyclic heterobase scaffold. Several analogues were
      prepared, including the McGuigan ProTide, however the parent nucleoside exhibited
      the best chemotherapeutic activity, specifically against breast cancer cell lines
      (89.53% growth inhibition). 

PMID- 26316466
TI  - Discovery of novel nonpeptide allosteric inhibitors interrupting the interaction
      of CDK2/cyclin A3 by virtual screening and bioassays.
AB  - Serine/threonine-specific cyclin-dependent kinases (CDKs) are key regulatory
      elements in eukaryotic cell cycle progression, and the dysregulation of CDKs has
      been implicated in cancers. Therefore, CDKs have been identified as anti-cancer
      targets for the development of small-molecule drugs. In this Letter, virtual
      screening and biological evaluation were performed to identify novel lead
      structures that allosterically disrupt the interaction between CDK2 and cyclin
      A3, which are directed toward a noncatalytic binding pocket of CDK2. Ultimately,
      B2 was identified as exhibiting superior CDK2/cyclin A3 inhibition activity. In
      addition, our results indicated that B2 exhibited antiproliferative activities
      against a broad spectrum of human cancer cell lines. Significantly, B2 certainly
      interrupted the interaction between CDK2 and cyclin A3 and exhibited a
      concentration-dependent trend. In summary, our results suggest that B2 is the
      first effective allosteric chemical small-molecule CDK2 inhibitor to be
      discovered, and further lead optimization may result in a series of novel anti
      CDK2 agents. 

PMID- 26316467
TI  - Dicarabrol, a new dimeric sesquiterpene from Carpesium abrotanoides L.
AB  - A new dimeric sesquiterpene, dicarabrol (1), together with three known
      sesquiterpenes, carabrol (2), 11(13)-dehydroivaxillin (3), and 2-desoxy-4-epi
      pulchellin (4), were isolated from the whole plant of Carpesium abrotanoides L.
      Their structures were elucidated on the basis of spectroscopic analysis, and
      single crystal X-ray diffraction analysis. Compound 1 possessed a dimeric
      sesquiterpene core featured with a cyclopentane ring connecting two sesquiterpene
      lactone units rarely discovered in nature. Dicarabrol (1), as well as three known
      sesquiterpenes (2-4), had potent in vitro cytotoxicities against the K562, MCF-7,
      Hela, DU145, U937, H1975, SGC-7901, A549, MOLT-4, and HL60 cell lines with IC50
      values ranging from 0.10 to 46.7 MUM, while they showed significant antiviral
      (H1N1 and H3N2) activities. Furthermore, compounds 1, 3 and 4 displayed
      significant antimycobacterial activity (IC50 3.7, 6.0, and 7.6 MUM,
      respectively).

PMID- 26316468
TI  - Design, synthesis and biological evaluation of multifunctional ligands targeting
      opioid and bradykinin 2 receptors.
AB  - We report here the design and synthesis of novel multifunctional ligands that act
      as (MU/delta) opioid agonists and bradykinin 2 receptor antagonists. These
      multifunctional ligands were designed to interact with the multiple receptors to
      show an enhanced analgesic effect, with no opioid-induced tolerance. We designed
      our multifunctional ligands based on the well-known second generation bradykinin
      2 receptor antagonist Hoe 140 (DArg-Arg-Pro-Hyp-Gly-Thi-Ser-DTic-Oic-Arg-OH) and
      the opioid enkephalin analogues Tyr-DAla-Phe, Tyr-DAla-Gly-Phe and Tyr-Pro-Phe.
      We explored the conjugation of opioid pharmacophore to the Hoe 140 (DArg-Arg-Pro
      Hyp-Gly-Thi-Ser-DTic-Oic-Arg-OH) in various positions with and without a linker.
      These bifunctional ligands showed very good binding affinity towards the both MU
      and delta opioid receptors. Among these bifunctional ligands 8, 11 and 12 showed
      excellent and balanced binding affinity at both MU and delta opioid receptors
      (0.5 nM, 2.0 nM; 0.3 nM, 2 nM; 2 nM and 3 nM), respectively. On the other hand
      these bifunctional ligands showed very weak and no binding affinity for rat brain
      bradykinin 2 receptors. Similarly, the Hoe 140 showed very low affinity (>10,000
      nM and 9,000 nM) against [(3)H] BK binding in rat brain membranes and in HEK293
      cells, respectively. In contrast, the Hoe 140 showed very good binding affinity
      in guinea pig ileum (0.43 nM) similar to that of previously reported. The
      bradykinin 2 receptors are known to be present in rat brain membrane, guinea pig
      ileum (GPI) and rabbit jugular vein. Previously the binding affinity of Hoe 140
      for bradykinin 2 receptor was reported using guinea pig ileum. The above results
      suggest that the bradykinin 2 receptors present in rat brain membrane are a
      different sub type than the bradykinin 2 receptor present in guinea pig ileum
      (GPI).

PMID- 26316470
TI  - The Evaluation of FDG PET/CT Scan Findings in Patients with Organizing Pneumonia
      Mimicking Lung Cancer.
AB  - OBJECTIVE: Organizing pneumonia (OP) is a rare lung condition that is
      characterized by the presence of polypoid tissues due to fibroblastic plugs
      within respiratory bronchioles, alveolar ducts and sacs. The three main
      radiologic patterns of OP include typical, solitary-focal and infiltrative forms.
      The maximum standardized uptake value (SUVmax) on positron emission tomography
      computed tomography (PET/CT) may be high in benign conditions such as OP as well
      as malignant diseases. The aim of our study was to investigate PET-CT
      characteristics of OP in patients mimicking lung cancer. METHODS: The clinical
      and radiologic characteristics of 50 patients who were referred to our hospital
      for PET/CT evaluation due to suspicion of lung malignancy, and who were
      pathologically diagnosed as OP between 2009 and 2013 were retrospectively
      reviewed. RESULTS: The mean age of the patients was 58.2 years. Ninety-six
      percent of patients (48) were male. Radiologic evaluation revealed 27 (54%) focal
      involvement, 10 (20%) consolidation with air-bronchogram (typical), 1 (2%)
      infiltrative and 12 (24%) other types of involvement (multiple nodules and
      cavitary lesions). The mean SUVmax value of the lesions on PET/CT was calculated
      as 6.5. Mediastinal lymph node involvement (at least one station) was detected in
      76% of our study group with a mean SUVmax value of 3.27. CONCLUSION: OP may cause
      false positive results on PET/CT. However, PET/CT results may be used as a guide
      for invasive procedures that should be performed when there is suspicion of
      malignancy.

PMID- 26316469
TI  - Nuclear Medicine in Thyroid Diseases in Pediatric and Adolescent Patients.
AB  - Both benign and malignant diseases of the thyroid are rare in the pediatric and
      adolescent population, except congenital hypothyroidism. Nuclear medicine plays a
      major role, both in the diagnosis and therapy of thyroid pathologies. Use of
      radioactivity in pediatric population is strictly controlled due to possible side
      effects such as secondary cancers; therefore, management of pediatric patients
      requires detailed literature knowledge. This article aims to overview current
      algorithms in the management of thyroid diseases and use of radionuclide therapy
      in pediatric and adolescent population. 

PMID- 26316471
TI  - Prevalence of Helicobacter Pylori Infection in School and Pre-School Aged
      Children with C-14 Urea Breath Test and the Association with Familial and
      Environmental Factors.
AB  - OBJECTIVE: To investigate the prevalence of Helicobacter pylori (Hp) infection in
      pre-school and school age children with C-14 urea breath test, and to explore its
      association with age and socioeconomic factors in Turkey. METHODS: Hp infection
      status was determined by using Urea Breath Test (UBT). Patients who had previous
      gastric surgery, Hp eradication treatment or equivocal UBT results were excluded.
      A questionnaire was administered to elicit information on gender, age, ABO/Rh
      blood group type, presence of gastric disease in the family, domestic animal in
      the household, and treatment for idiopathic Iron Deficiency Anemia (IDA).
      RESULTS: This retrospective study included 500 pediatric patients (179 boys, 321
      girls, mean age 10.7+/-4.3 years) of whom 62 (12.4%) were aged <=6 years and 438
      (87.6%) were aged 7 to 16 years. Helicobacter pylori (Hp) was positive in 245
      (49%) cases. In the pre-school age group, 21/62 cases (34%) had positive UBT
      while in the school age group 224/438 children (51%) had positive UBT. A family
      history of dyspepsia and pet ownership were not associated with Hp positivity. Hp
      positive 76 (29.8%) children were on IDA treatment but this was not statistically
      significant. CONCLUSION: The Hp infection positivity rate was 49% in the
      pediatric age study group. The positivity rate was significantly lower at
      preschool age than school age, and it increased with age. There was no
      association with gender, ABO/Rh blood groups, presence of domestic pets, IDA, or
      history of gastric disease in the family.

PMID- 26316472
TI  - Proliferative and Glycolytic Assessment of the Whole-Body Bone Marrow
      Compartment.
AB  - OBJECTIVE: Quantitative assessment of active bone marrow (BM) in vivo is yet to
      be well-defined. This study aims to compare total body BM volume estimations
      obtained from use of both18F-FLT PET/CT and 18F-FDG PET/CT in order to
      consolidate higher cellular proliferation rates with imaging the highly active
      red BM in pancreatic cancer. METHODS: This phase I pilot study includes seven
      patients with pancreatic cancers who underwent both 18F-FLT and 18F-FDG imaging
      each acquired within a week's duration. A CT-based classifier is used for
      segmenting bone into cortical and trabecular regions. The total BM volume is
      determined through statistical thresholding on PET activity found within the
      trabecular bone. RESULTS: Results showed that 18F-FLT measures of red BM volume
      (RBV) were higher than those obtained from 18F-FDG (?=89.21 ml). RBV obtained
      using 18F-FLT in males were found to have high correlation with measured weight
      (R2=0.61) and BMI (R2=0.70). The red BM fraction obtained from 18F-FLT was
      significantly different between males and females, with females showing much
      higher red bone matter within the trabecular bone (p<0.05). In contrast to 18F
      FLT, 18F-FDG BM measurements showed that RBV was significantly different between
      males and females (p<0.05). Results also show that spinal activity SUV threshold
      for red BM segmentation is significantly different between 18F-FLT PET and 18F
      FDG PET (p<0.05). CONCLUSION: By combining 18F-FLT-PET and 18F-FDG-PET, this
      study provides useful insights for in vivo BM estimation through its
      proliferative and glycolytic activities.

PMID- 26316473
TI  - Clinical Significance of Lymphoscintigraphy Findings in the Evaluation of Lower
      Extremity Lymphedema.
AB  - OBJECTIVE: The purpose of this study was to investigate the clinical significance
      of lymphoscintigraphy imaging in the evaluation of lower extremity lymphedema.
      METHODS: Technetium-99m-labeled nanocolloid was injected subcutaneously in the
      first web spaces of both feet of 123 patients (M/F: 43/80, mean age 57.5+/-13.1
      years, range 16-78 years) who had clinical evidence of lower extremity swelling
      with suspicion of lymphedema, and were referred for routine lymphoscintigraphy.
      Lymphoscintigraphy scan was started as dynamic viewing followed by static whole
      body imaging at 10 minute, 1 hour and 4 hours after injection. RESULTS: Eighty
      seven patients had lymphedema. Patients who had lymphedema were divided into two
      groups according to their scintigraphy findings: Group I included 58 patients
      without uptake in the popliteal nodes, and group II included 29 patients with
      positive popliteal nodes. The rate of popliteal node visualization was higher in
      patients with dermal backflow as compared to those without dermal backflow
      (p<0.001). The duration of lymphedema was also longer in patients with dermal
      backflow and popliteal nodes (p<0.004). CONCLUSION: Lymphoscintigraphy is a
      reliable, easily applied and well-tolerated objective method to diagnose lower
      extremity lymphedema. Uptake by popliteal lymph nodes and the presence of dermal
      backflow on lymphoscintigraphy, which is performed for evaluation of the lower
      limb lymphedema, were important signs indicating longer disease duration and
      higher severity of lymphatic dysfunction.

PMID- 26316474
TI  - Unexpected Uptake by the Gallbladder in Post-Ablative I-131 Scan.
AB  - A 47-year-old woman was diagnosed as papillary thyroid carcinoma. I-131 ablation
      therapy was applied following total thyroidectomy, and the whole-body scan
      revealed a focus of increased uptake in the right upper quadrant. Lateral view
      images of the uptake site showed that the focus was located near the right liver
      lobe. The patient was referred to radiology department for correlative abdominal
      Computed Tomography (CT) and Ultrasonography (US) to rule out a possible liver
      metastasis. CT images detected a gallstone in the corresponding area, which was
      verified by US. These methods did not reveal any metastatic disease in the liver
      or in other abdominal organs. This is the first published case report documents a
      rare false-positive finding of I-131 scan that was associated with an
      asymptomatic gallstone, and emphasizes the importance of correlative imaging in
      gallbladder related I-131 uptake. 

PMID- 26316475
TI  - Visualization of Gallbladder with In-111 Octreotide Scan.
AB  - A 54-year-old woman underwent octreotide scintigraphy for evaluation of
      neuroendocrine tumor recurrence. The images demonstrated unusual uptake in
      gallbladder area in addition to physiologic uptake at other tissues. Whole-body
      planar and SPECT imaging were repeated after fatty meal ingestion at 28 hours in
      order to figure out whether this activity was physiologic or not. Since the
      unusual uptake in the gallbladder was still detected at these images, additional
      images were obtained 72 hours after radionuclide injection. The activity in the
      gallbladder disappeared at these images revealing the physiologic nature of this
      unusual accumulation. 

PMID- 26316476
TI  - Sentinel Lymph Node Detection in Contralateral Axilla at Initial Presentation of
      a Breast Cancer Patient: Case Report.
AB  - The main basin for breast lymphatic drainage is ipsilateral axilla. However,
      extra-axillary drainage may be seen in some patients. The most common extra
      axillary site is internal mammary chain, while contralateral axillary drainage is
      an extremely rare situation in previously untreated patients. We describe a case
      of untreated right breast retroareolar carcinoma with contralateral axillary
      drainage detected on preoperative lymphoscintigraphy. Contralateral axillary
      dissection was performed based on the result of frozen section examination of the
      sentinel lymph node (SLN) which turned out to burden micrometastasis.
      Postoperative histopathological examination revealed invasive ductal carcinoma
      metastasis in 17 out of 22 lymph nodes from the ipsilateral axillary dissection,
      whereas 14 lymph nodes from contralateral axillary dissection other than the SLN
      were nonmetastatic. In our opinion, determination of contralateral axillary
      metastasis in primary staging process had a major contribution to the management
      of the patient. 

PMID- 26316477
TI  - Over-the-counter sales of out-of-state and counterfeit tax stamp cigarettes in
      New York City.
AB  - BACKGROUND: New York City (NYC) has strict minimum cigarette price and tax stamp
      laws, but evidence regarding the extent of evasion of such laws in over-the
      counter sales is scarce. METHODS: 830 packs were purchased at licensed tobacco
      retailers at 92 randomly selected neighbourhoods in NYC in spring and fall 2014,
      following the establishment of NYC's minimum price law. The chi(2) analyses of
      illegal tax stamps on pack, by retailer type and data collection period, are
      presented. RESULTS: Over 15% of packs purchased had out-of-state (4.5%) or
      counterfeit tax stamps (10.6%). Purchases resulted in at least one illegal pack
      obtained in 70% of neighbourhoods, largely from independent stores. In 21.5% of
      sampled neighbourhoods, it was possible to purchase an illegal pack each
      collection period. CONCLUSIONS: Enhanced enforcement of retail sales of
      cigarettes is needed to ensure the full benefit of existing tobacco control laws
      in NYC.

PMID- 26316478
TI  - Recommendations for Risk Categorization and Prophylaxis of Invasive Fungal
      Diseases in Hematological Malignancies: A Critical Review of Evidence and Expert
      Opinion (TEO-4).
AB  - This is the last of a series of articles on invasive fungal infections prepared
      by opinion leaders in Turkey. The aim of these articles is to guide clinicians in
      managing invasive fungal diseases in hematological malignancies and stem cell
      transplantation based on the available best evidence in this field. The previous
      articles summarized the diagnosis and treatment of invasive fungal disease and
      this article aims to explain the risk categorization and guide the antifungal
      prophylaxis in invasive fungal disease. 

PMID- 26316481
TI  - The Hematological and Molecular Spectrum of alpha-Thalassemias in Turkey: The
      Hacettepe Experience.
AB  - OBJECTIVE: The spectrum of alpha-thalassemias correlates well with the number of
      affected alpha-globin genes. Additionally, combinations of the several non
      deletional types of mutations with a large trans deletion comprising the 2 alpha
      globin genes have an impact on the clinical severity. The objective of this study
      was to analyze the hematological and molecular data of 35 patients with Hb H
      disease from a single center in order to identify the genotypes of Hb H disease
      and genotype-phenotype correlations. MATERIALS AND METHODS: Herein, we report the
      hematological and mutational spectrum of patients with Hb H disease (n=35).
      Additionally, genotypes of alpha-gene mutations of 78 individuals, who were
      referred to our institution for alpha-gene screening, were analyzed. RESULTS:
      Supporting the previous data from Turkey, -alpha3.7 was the most common mutation
      among patients with Hb H disease (62.8%) and in the other 78 subjects (39.7%). Of
      the patients with Hb H disease, the most common genotypes were -alpha3.7/--20.5, 
      alpha3.7/--26.5, and -alpha3.7/--17.5 in 10 (28.6%), 6 (17.1%), and 6 (17.1%)
      patients, respectively. Another small deletion, -4.2 alpha, and several non
      deletional types of alpha-gene mutations, namely alpha (-5nt): IVS-I donor site
      (GAG.GTG.AGG->GAG.G-----); alpha (PA-2): AATAAA>AATGGA, and alpha (cd59): GGC
      >GAC, were found to be associated with Hb H disease when present at trans loci of
      one of the large deletions given above. The combinations consisting of 1 non
      deletional and 1 of the large deletional types of mutations (alphaTalpha/--) at
      trans loci were found to result in a more severe phenotype compared to the
      genotypes composed of 1 small trans deletion of a large deletion (-alpha/--). The
      combination of alpha (Cd59) and -- in trans was associated with severe phenotype
      and the disease was associated with an increase in Hb Bart's level with null Hb
      H. In spite of the presence of 2 intact alpha-globin genes, homozygosity for PA-2
      mutation resulted in severe Hb H disease. CONCLUSION: This study indicated that
      Hb H disease is not rare in Turkey and its genotype is quite heterogeneous.

PMID- 26316480
TI  - A Possible Role for WNT5A Hypermethylation in Pediatric Acute Lymphoblastic
      Leukemia.
AB  - OBJECTIVE: WNT5A is one of the most studied noncanonical WNT ligands and is shown
      to be deregulated in different tumor types. Our aim was to clarify whether
      hypermethylation might be the cause of low WNT5A mRNA levels and whether we could
      restore this downregulation by reversing the event. MATERIALS AND METHODS: The
      expression of WNT5A mRNA was studied in a large acute lymphoblastic leukemia
      (ALL) patient group (n=86) by quantitative real-time PCR. The methylation status
      was detected by methylation-specific PCR (MSPCR) and bisulphate sequencing. In
      order to determine whether methylation has a direct effect on WNT5A expression,
      disease-representative cell lines were treated by 5'-aza-20-deoxycytidine.
      RESULTS: Here we designed a validation experiment of the WNT5A gene, which was
      previously examined and found to be differentially expressed by microarray study
      in 31 T-cell ALL patients. The expression levels were confirmed by quantitative
      real-time PCR and the expression levels were significantly lower in T-cell ALL
      patients than in control thymic subsets (p=0.007). MSPCR revealed that 86% of the
      patients were hypermethylated in the WNT5A promoter region. Jurkat and RPMI cell
      lines were treated with 5'-aza-20-deoxycytidine and WNT5A mRNA expression was
      restored after treatment. CONCLUSION: According to our results, WNT5A
      hypermethylation does occur in ALL patients and it has a direct effect on mRNA
      expression. Our findings show that epigenetic changes of WNT signaling can play a
      role in ALL pathogenesis and reversing methylation might be useful as a possible
      treatment of leukemia.

PMID- 26316479
TI  - A Novel Natural Product, KL-21, Inhibits Proliferation and Induces Apoptosis in
      Chronic Lymphocytic Leukemia Cells.
AB  - OBJECTIVE: The aims of this study were to examine the cytotoxic and apoptotic
      effects of KL-21, a novel plant product (produced by Naturin Natural Products,
      Izmir, Turkey), on 232B4 chronic lymphocytic leukemia (CLL) cells and to
      determine the cytotoxic effects on healthy BEAS-2B human bronchial epithelial
      cells. MATERIALS AND METHODS: The cytotoxic effect of KL-21 was determined by MTT
      cell proliferation assay. Changes in caspase-3 enzyme activity were measured
      using the caspase-3 colorimetric assay. Changes in mitochondrial membrane
      potential were determined using the JC-1 dye-based method. Annexin V-FITC/PI
      double staining was performed to measure the apoptotic cell population. Effects
      of KL-21 on cell cycle profiles of CLL cells were investigated by flow cytometry.
      RESULTS: We detected time- and concentration-dependent increases in the cytotoxic
      effect of KL-21 on 232B4 CLL cells. However, we also showed that, especially at
      higher concentrations, KL-21 was less cytotoxic towards BEAS-2B healthy cells
      than towards CLL cells. Annexin-V/PI double staining results showed that the
      apoptotic cell population increased in 232B4 cells. Increasing concentrations of
      KL-21 increased caspase-3 enzyme activity and induced loss of mitochondrial
      membrane potential. KL-21 administration resulted in small increases in the
      percentage of the cells in the G0/G1 phase while it decreased the S phase cell
      population up to 1 mg/mL. At the highest concentration, most of the cells
      accumulated in the G0/G1 phase. CONCLUSION: KL-21 has a growth-inhibitory effect
      on 232B4 CLL cells. KL-21 causes apoptosis and cell cycle arrest at G0/G1.

PMID- 26316483
TI  - The Effect of FcgammaRIIIA Gene Polymorphism on the Treatment of Diffuse Large B
      cell Non-Hodgkin Lymphoma: A Multicenter Prospective Observational Study.
AB  - OBJECTIVE: The curative treatment approach for diffuse large B-cell lymphoma
      (DLBCL) is controversial even in the rituximab (R) era. The aim of this study was
      to examine the FcgammaRIIIA gene polymorphism distribution of DLBCL patients who
      had been treated with R-CHOP (cyclophosphamide, doxorubicin, vincristine, and
      prednisone) chemotherapy. Furthermore, we investigated the impact of FcgammaRIIIA
      gene polymorphism on the overall response rate (ORR) and overall survival (OS).
      MATERIALS AND METHODS: Patients from 3 centers in the Aegean region of Turkey who
      had newly diagnosed CD20-positive DLBCL were enrolled in the study. The single
      nucleotide polymorphisms of the FcgammaRIIIA gene were analyzed by real time-PCR.
      The response to treatment was determined in the middle and at the end of the
      protocol. During 2 years of follow-up, the patients were clinically and
      radiologically evaluated for disease status every 3 months. RESULTS: Thirty-six
      patients were included in the study and the distributions of F/F, V/F, and V/V
      types of alleles of FcgammaRIIIA were 25%, 50%, and 25%, respectively. Twenty
      seven patients were considered as evaluable according to ORR and OS. The
      patients' ORR was 87.5%, 100%, and 50% in the F/F, V/F, and V/V allele groups,
      respectively. We did not establish any statistically significant differences
      among the 3 alleles groups in respect to ORR (p=0.93). The OS within 2 years in
      the F/F, V/F, and V/V allele groups was 62.5%, 100%, and 100%, respectively. The
      OS in the F/F allele group was found to be lower than in the other 2 allele
      groups (p=0.01). CONCLUSION: The distribution of gene polymorphisms in our study
      group was similar to those of previous studies. While ORR was similar between the
      groups, our results highlight a lower OS in F/F patients compared to other allele
      groups of FcgammaRIIIA.

PMID- 26316482
TI  - Cohort Study: Central Venous Catheter-Related Complications in Children with
      Hematologic Diseases at a Single Center.
AB  - OBJECTIVE: This study aims to document and analyze the central venous catheter
      (CVC)-related complications in children with hematological diseases who were
      treated within a single institution. MATERIALS AND METHODS: A retrospective
      investigation was conducted in 106 pediatric patients in whom 203 CVCs were
      inserted. A total of 175 catheter-related complications occurred in 5 years.
      RESULTS: The rates of clinical catheter infections, local catheter infections,
      venous thromboembolism, bleeding, and mechanical complications were 2.6, 1.1,
      0.2, 0.2, and 0.2 per 1000 catheter days. Methicillin-resistant Staphylococcus
      epidermidis was the predominant infectious organism in blood and catheter
      cultures. The children with leukemia had a significantly higher frequency of
      clinical catheter infections (p=0.046). The children who underwent bone marrow
      transplantation had a significantly lower frequency of clinical catheter
      infections (p=0.043) and higher frequency of local catheter infections (p=0.003).
      The children with implanted catheters had a significantly lower frequency of
      clinical catheter infections (p=0.048). The children with thrombocytopenia had
      significantly fewer local catheter infections and significantly more clinical
      catheter infections and catheter-related bleeding (respectively p=0.001, p=0.042,
      and p=0.024). CONCLUSION: Leukemia, bone marrow transplantation, and
      thrombocytopenia are risk factors for CVC-associated complications. The
      relatively higher number of interventions performed via permanent catheters may
      be responsible for the significantly increased incidence of systemic infections
      and mechanical injury.

PMID- 26316484
TI  - Presence of Essential Hypertension or Diabetes Mellitus Is a Predictor of
      Intracranial Bleeding in Elderly Patients: A Study of 108 Patients with Isolated
      Thrombocytopenia from a Single Reference Center.
AB  - OBJECTIVE: Thrombocytopenia poses a significant problem in the elderly. Not only
      are there varied causes, but it is also associated with significant morbidity and
      mortality. We carried out a study to learn the causes of isolated
      thrombocytopenia in elderly patients and to correlate the severity of
      thrombocytopenia and bleeding manifestations with various etiologic factors and
      comorbidities. MATERIALS AND METHODS: A total of 108 patients above 50 years of
      age presenting with isolated thrombocytopenia (platelet counts of <100x109/L with
      normal hemoglobin and total leukocyte counts) were enrolled in the study.
      Detailed history and clinical examinations were carried out for each patient.
      Complete blood counts were analyzed by automated cell counter. Peripheral smears
      were examined in all cases. HbsAg, anti-HCV, and anti-HIV testing by enzyme
      linked immunosorbent assay was done in all patients. Wherever clinically
      indicated, bone marrow aspiration biopsy and cytogenetic studies were done.
      RESULTS: Out of 108 patients, 102 (94.4%) presented with bleeding tendencies.
      Twenty-nine (26.8%) presented with serious (World Health Organization grade 3/4)
      bleedings. Major findings were immune thrombocytopenic purpura in 79 (73.1%),
      myelodysplastic syndrome in 7 (6.5%), drug-induced thrombocytopenia in 7 (6.5%),
      and connective tissue disorder in 4 (3.7%) cases. Ten patients presented with
      intracranial bleedings. Upon logistic regression analysis, comorbidities in the
      form of essential hypertension and diabetes mellitus were significantly
      associated with occurrence of intracranial bleeding. There was no correlation of
      serious bleedings with platelet counts. CONCLUSION: Isolated thrombocytopenia in
      the elderly is associated with significant morbidity. Diligent clinical and
      laboratory evaluation is required to elucidate the cause of thrombocytopenia in
      the elderly. Comorbidities in this population are associated with serious
      bleedings and not low platelet counts as is commonly thought.

PMID- 26316485
TI  - Pharmacobiological Approach for the Clinical Development of Ruxolitinib in
      Myeloproliferative Neoplasms.
AB  - Ruxolitinib, a JAK1 and JAK2 inhibitor drug, has recently been approved for the
      treatment of patients with high- or intermediate-risk myelofibrosis with
      symptomatic splenomegaly. Ruxolitinib is the first clinically useful targeted
      therapy in Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs).
      The aim of this paper is to indicate pharmacobiological aspects of ruxolitinib
      within the potential context of MPNs. Pharmacobiological assessments, in addition
      to knowledge of the risk profile for ruxolitinib in MPNs, are required. We
      propose hypotheses based on our experience in a splenectomized MPN patient with
      hyperproliferative bone marrow and moderate fibrosis receiving ruxolitinib. We
      believe that a true clinical development approach for this drug should include
      pharmacobiological assessments for ruxolitinib in addition to the disease risk
      profile of MPNs. 

PMID- 26316486
TI  - Possible Role of Interleukin-31/33 Axis in Imatinib Mesylate-Associated Skin
      Toxicity.
AB  - Imatinib mesylate is a small-molecule tyrosine kinase inhibitor (TKi) designed to
      target c-ABL and BCR-ABL, approved for the treatment of chronic myeloid leukemia
      and gastrointestinal stromal tumors. Adverse cutaneous reactions induced by
      imatinib are frequent, generally moderate, and dose-dependent. The aim of this
      work was to investigate the possible contribution of interleukin (IL)-33 and IL
      31, cytokines involved in disorders associated with itching, in the pathogenesis
      of pruritus in a patient undergoing imatinib mesylate treatment. His IL-31 and IL
      33 serum levels were significantly higher than in the control group (respectively
      96.6 pg/mL vs. 7.623+/-7.681 pg/mL and 27.566 pg/mL vs. 6.170+/-7.060 pg/mL). In
      light of these findings, imatinib mesylate-related symptoms of dermatologic
      toxicities might be related to the release of IL-31 and IL-33. In particular, it
      is supposable that TKi usage could cause keratinocyte injury, the release of IL
      33, and the consequent interaction with its receptor on mast cells that induces
      the secretion of several factors capable of causing skin manifestations,
      including IL-31, a known pruritus-inducing cytokine. This report, to the best of
      our knowledge, is the first work describing the possible involvement of the IL
      31/IL-33 axis in the pathogenesis of skin side effects related to imatinib
      mesylate treatment. 

PMID- 26316487
TI  - Severe Clinical Course in a Patient with Congenital Amegakaryocytic
      Thrombocytopenia Due to a Missense Mutation of the c-MPL Gene.
AB  - Congenital amegakaryocytic thrombocytopenia (CAMT) generally begins at birth with
      severe thrombocytopenia and progresses to pancytopenia. It is caused by mutations
      in the thrombopoietin receptor gene, the myeloproliferative leukemia virus
      oncogene (c-MPL). The association between CAMT and c-MPL mutation type has been
      reported in the literature. Patients with CAMT have been categorized according to
      their clinical symptoms caused by different mutations. Missense mutations of c
      MPL have been classified as type II and these patients have delayed onset of bone
      marrow failure compared to type I patients. Here we present a girl with severe
      clinical course of CAMT II having a missense mutation in exon 4 of the c-MPL gene
      who was admitted to our hospital with intracranial hemorrhage during the newborn
      period. 

PMID- 26316488
TI  - Management of Two Juvenile Myelomonocytic Leukemia Patients According to Clinical
      and Genetic Features.
AB  - Juvenile myelomonocytic leukemia (JMML) is a rare clonal myeloproliferative
      disorder of childhood. Major progress has been achieved in diagnosis and the
      understanding of the pathogenesis of JMML by identifying the genetic pathologies
      that occur in patients. Mutations of RAS, NF1, PTPN11, and CBL are found in
      approximately 80% of JMML patients. Distinct clinical features have been reported
      to be associated with specific gene mutations. The advent of genomic studies and
      recent identification of novel genetic mutations in JMML are important not only
      in diagnosis but also in the management and prognosis of the disease. Herein, we
      present 2 patients with JMML harboring different mutations, NRAS and c-CBL,
      respectively, with distinct clinical features and different therapeutic
      approaches. 

PMID- 26316489
TI  - Ruxolitinib Treatment in a Patient with Primary Myelofibrosis Resistant to
      Conventional Therapies and Splenectomy: A Case Report.
AB  - A 67-year-old male patient who was diagnosed with primary myelofibrosis 4 years
      ago did not respond to conventional therapies. The splenomegaly progressively
      increased, which caused spleen infarctions and led to the decision to perform a
      splenectomy procedure. After splenectomy, the patient started treatment with
      ruxolitinib. In the first month of ruxolitinib treatment, the patient became
      transfusion-free and all constitutional symptoms disappeared. However, in the
      sixth month of ruxolitinib treatment, the disease transformed to acute
      myeloblastic leukemia, and the patient died 1 month later. This is the first case
      report that shows the effects of ruxolitinib in a splenectomized patient. 

PMID- 26316490
TI  - Thiopurine S-Methyltransferase and Methylenetetrahydrofolate Reductase
      Polymorphisms in Leukemia.

PMID- 26316491
TI  - Platelet Levels of High- and Mega-Dose Methylprednisolone Treatment in Acute
      Immune Thrombocytopenia.

PMID- 26316492
TI  - Gaucher Disease and Gaucher Cells.

PMID- 26316493
TI  - Terbinafine and Neutropenia.

PMID- 26316494
TI  - Multiple Myeloma and Alkaline Phosphatase.

PMID- 26316495
TI  - Disseminated Histoplasmosis in an Immunocompetent Host Presenting as Pancytopenia
      with Bilateral Adrenal Masses.

PMID- 26316496
TI  - Promyelocytic Blastic Crisis in Chronic Myeloid Leukemia During Imatinib
      Treatment.

PMID- 26316497
TI  - Late Conversion After Sac Anchoring Endoprosthesis for Secondary Aortic Aneurysm
      Infection.
AB  - PURPOSE: To demonstrate explantation of the Nellix Endovascular Aneurysm Sealing
      (EVAS) System in the setting of infection. CASE REPORTS: Two male patients, 71
      and 83 years old, underwent Nellix implantation for asymptomatic infrarenal
      aortic aneurysms measuring 5.1 and 6.3 cm, respectively. Each developed late
      infections at 8 and 4 months post EVAS, respectively. The first patient
      experienced aneurysm rupture after medical therapy failed; the Nellix endosystem
      was explanted in an uneventful procedure. The second patient developed an
      aortoduodenal fistula, which was sutured before the Nellix device was removed
      without complications. The patient died 3 months later, presumably due to ongoing
      infection. CONCLUSION: The need to explant a Nellix EVAS System due to graft
      infection is a straightforward procedure compared to the removal of a
      conventional endograft with suprarenal fixation. It requires only temporary
      suprarenal clamping. The devices can be easily removed due to the lack of
      penetrating components and without damage to the aortic segment needed to create
      an anastomosis.

PMID- 26316498
TI  - gamma-Tubulin complexes in microtubule nucleation and beyond.
AB  - Tremendous progress has been made in understanding the functions of gamma-tubulin
      and, in particular, its role in microtubule nucleation since the publication of
      its discovery in 1989. The structure of gamma-tubulin has been determined, and
      the components of gamma-tubulin complexes have been identified. Significant
      progress in understanding the structure of the gamma-tubulin ring complex and its
      components has led to a persuasive model for how these complexes nucleate
      microtubule assembly. At the same time, data have accumulated that gamma-tubulin
      has important but less well understood functions that are not simply a
      consequence of its function in microtubule nucleation. These include roles in the
      regulation of plus-end microtubule dynamics, gene regulation, and mitotic and
      cell cycle regulation. Finally, evidence is emerging that gamma-tubulin mutations
      or alterations of gamma-tubulin expression play an important role in certain
      types of cancer and in other diseases. 

PMID- 26316501
TI  - Neonatal Public Health: Progress and Challenges.

PMID- 26316499
TI  - Apps for IMproving FITness and Increasing Physical Activity Among Young People:
      The AIMFIT Pragmatic Randomized Controlled Trial.
AB  - BACKGROUND: Given the global prevalence of insufficient physical activity (PA),
      effective interventions that attenuate age-related decline in PA levels are
      needed. Mobile phone interventions that positively affect health (mHealth) show
      promise; however, their impact on PA levels and fitness in young people is
      unclear and little is known about what makes a good mHealth app. OBJECTIVE: The
      aim was to determine the effects of two commercially available smartphone apps
      (Zombies, Run and Get Running) on cardiorespiratory fitness and PA levels in
      insufficiently active healthy young people. A second aim was to identify the
      features of the app design that may contribute to improved fitness and PA levels.
      METHODS: Apps for IMproving FITness (AIMFIT) was a 3-arm, parallel, randomized
      controlled trial conducted in Auckland, New Zealand. Participants were recruited
      through advertisements in electronic mailing lists, local newspapers, flyers
      posted in community locations, and presentations at schools. Eligible young
      people aged 14-17 years were allocated at random to 1 of 3 conditions: (1) use of
      an immersive app (Zombies, Run), (2) use of a nonimmersive app (Get Running), or
      (3) usual behavior (control). Both smartphone apps consisted of a fully automated
      8-week training program designed to improve fitness and ability to run 5 km;
      however, the immersive app featured a game-themed design and narrative. Intention
      to-treat analysis was performed using data collected face-to-face at baseline and
      8 weeks, and all regression models were adjusted for baseline outcome value and
      gender. The primary outcome was cardiorespiratory fitness, objectively assessed
      as time to complete the 1-mile run/walk test at 8 weeks. Secondary outcomes were
      PA levels (accelerometry and self-reported), enjoyment, psychological need
      satisfaction, self-efficacy, and acceptability and usability of the apps.
      RESULTS: A total of 51 participants were randomized to the immersive app
      intervention (n=17), nonimmersive app intervention (n=16), or the control group
      (n=18). The mean age of participants was 15.7 (SD 1.2) years; participants were
      mostly NZ Europeans (61%, 31/51) and 57% (29/51) were female. Overall retention
      rate was 96% (49/51). There was no significant intervention effect on the primary
      outcome using either of the apps. Compared to the control, time to complete the
      fitness test was -28.4 seconds shorter (95% CI -66.5 to 9.82, P=.20) for the
      immersive app group and -24.7 seconds (95% CI -63.5 to 14.2, P=.32) for the
      nonimmersive app group. No significant intervention effects were found for
      secondary outcomes. CONCLUSIONS: Although apps have the ability to increase reach
      at a low cost, our pragmatic approach using readily available commercial apps as
      a stand-alone instrument did not have a significant effect on fitness. However,
      interest in future use of PA apps is promising and highlights a potentially
      important role of these tools in a multifaceted approach to increase fitness,
      promote PA, and consequently reduce the adverse health outcomes associated with
      insufficient activity. TRIAL REGISTRATION: Australian New Zealand Clinical Trials
      Registry: ACTRN12613001030763;
      https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=1261300103076
      (Archived by WebCite at http://www.webcitation.org/6aasfJVTJ).

PMID- 26316500
TI  - A Cross-sectional Study on Posttraumatic Stress Disorder and General Psychiatric
      Morbidity Among Adult Survivors 3 Years After the Wenchuan Earthquake, China.
AB  - After the Wenchuan earthquake, a large number of studies have focused on
      postearthquake psychological disorders among survivors; however, most of these
      studies were conducted within a relatively short period. This study was conducted
      to examine the symptoms of posttraumatic stress disorder (PTSD) and general
      psychiatric morbidity among adult survivors 3 years after the Wenchuan
      earthquake, China. Through a multistage systematic sampling approach, a cross
      sectional survey of 360 participants, 18 years or older, was conducted. The
      prevalence of PTSD and general psychiatric morbidity was 10.3% and 20.6%,
      respectively. Multivariate analysis revealed significant predictors for PTSD,
      including female gender and having felt guilt concerning someone's death or
      injury. Significant predictors for general psychiatric morbidity included
      unmarried status and having been in serious danger. These results suggest that
      mental health services should be continuously available to earthquake survivors. 

PMID- 26316502
TI  - Utilization of Comprehensive Health Insurance Scheme, Kerala: A Comparative Study
      of Insured and Uninsured Below-Poverty-Line Households.
AB  - We aimed to compare the sociodemographics, health care utilization pattern, and
      out-of-pocket (OOP) expenses of 149 insured and 147 uninsured below-poverty-line
      households insured under the Comprehensive Health Insurance Scheme, Kerala,
      through a comparative cross-sectional study. Family size more than 4 (odds ratio
      [OR] = 2.34; 95% confidence interval [CI] = 1.13-4.82), family member with
      chronic disease (OR = 2.05; 95% CI = 1.18-3.57), high socioeconomic status (OR =
      2.95; 95% CI = 1.74-5.03), and an employed household head (OR = 2.69; 95% CI =
      1.44-5.02) were significantly associated with insured households. Insured
      households had higher inpatient service utilization (OR = 1.57; 95% CI = 1.05
      2.34). Only 40% of inpatient service utilization among the insured was covered by
      insurance. The mean OOP expenses for inpatient services among insured (INR
      448.95) was higher than among uninsured households (INR 159.93); P = .003. These
      findings show that urgent attention of the government is required to redesign and
      closely monitor the scheme. 

PMID- 26316503
TI  - Chhaupadi Culture and Reproductive Health of Women in Nepal.
AB  - Different sociocultural barriers concerning women's health are still prevalent.
      Chhaupadi culture in Nepal is that threat wherein menstruating women have to live
      outside of the home in a shed-like dwelling. Our study aims to determine the
      factors of reproductive health problems related to Chhaupadi. A cross-sectional
      study was performed with women of menstrual age (N = 672) in Kailali and Bardiya
      districts of Nepal. Data were collected with stratified sampling and analyzed
      using SPSS. Reproductive health problems were observed according to the World
      Health Organization reproductive health protocol. Regression analysis was
      performed to show the association between relevant variables. Results reveal that
      one fifth (21%) of households used Chhaupadi. Condition of livelihood, water
      facility, and access during menstruation and precisely the Chhaupadi stay was
      associated (P < .001) with the reproductive health problems of women. The study
      concludes that Chhaupadi is a major threat for women's health. Further research
      on appropriate strategies against Chhaupadi and menstrual hygiene should be
      undertaken. 

PMID- 26316508
TI  - Hydration and outcome in older patients admitted to hospital (The HOOP
      prospective cohort study).
AB  - BACKGROUND: Older adults are susceptible to dehydration due to age-related
      pathophysiological changes. We aimed to investigate the prevalence of
      hyperosmolar dehydration (HD) in hospitalised older adults, aged >=65 years,
      admitted as an emergency and to assess the impact on short-term and long-term
      outcome. METHODS: This prospective cohort study was performed on older adult
      participants who were admitted acutely to a large U.K. teaching hospital. Data
      collected included the Charlson comorbidity index (CCI), national early warning
      score (NEWS), Canadian Study of Health and Aging (CSHA) clinical frailty scale
      and Nutrition Risk Screening Tool (NRS) 2002. Admission bloods were used to
      measure serum osmolality. HD was defined as serum osmolality >300 mOsmol/kg.
      Participants who were still in hospital 48 h after admission were reviewed, and
      the same measurements were repeated. RESULTS: A total of 200 participants were
      recruited at admission to hospital, 37% of whom were dehydrated. Of those
      dehydrated, 62% were still dehydrated when reviewed at 48 h after admission.
      Overall, 7% of the participants died in hospital, 79% of whom were dehydrated at
      admission (P = 0.001). Cox regression analysis adjusted for age, gender, CCI,
      NEWS, CSHA and NRS demonstrated that participants dehydrated at admission were 6
      times more likely to die in hospital than those euhydrated, hazards ratio (HR)
      6.04 (1.64-22.25); P = 0.007. CONCLUSIONS: HD is common in hospitalised older
      adults and is associated with poor outcome. Coordinated efforts are necessary to
      develop comprehensive hydration assessment tools to implement and monitor a real
      change in culture and attitude towards hydration in hospitalised older adults.

PMID- 26316509
TI  - Multicomponent delirium prevention: not as effective as NICE suggest?
AB  - Multicomponent delirium prevention strategies have been shown in intervention
      studies consistently to reduce the occurrence of delirium. Based on this
      convincing evidence base, the National Institute for Health and Care Excellence
      has advocated the widespread adoption of multicomponent delirium prevention
      interventions into the routine inpatient care of older people. However, despite
      successful reductions in incident delirium of about a third, anticipated
      reductions in mortality or admissions to long-term care--both clinically
      important endpoints statistically correlated with the occurrence of delirium-
      have not been conclusively observed. We hypothesise that the reasons for this
      disconnection are partly methodological, due to difficulties in delirium
      detection and blinding of study personnel to the intervention, but predominantly
      due to the underlying relationship between delirium and the abnormal health state
      of frailty; the interaction between these two geriatric syndromes is currently
      poorly understood.

PMID- 26316510
TI  - Effect of age on long-term facilitation and chemosensitivity during NREM sleep.
AB  - The reason for increased sleep-disordered breathing with a predominance of
      central apneas in the elderly is unknown. We speculate that ventilatory control
      instability may provide a link between aging and the onset of unstable breathing
      during sleep. We sought to investigate potential underlying mechanisms in
      healthy, elderly adults during sleep. We hypothesized that there is 1) a decline
      in respiratory plasticity or long-term facilitation (LTF) of ventilation and/or
      2) increased ventilatory chemosensitivity in older adults during non-, this
      should be hyphenated, non-rapid rapid eye movement (NREM) sleep. Fourteen elderly
      adults underwent 15, 1-min episodes of isocapnic hypoxia (EH), nadir O2
      saturation: 87.0 +/- 0.8%. Measurements were obtained during control, hypoxia,
      and up to 20 min of recovery following the EH protocol, respectively, for minute
      ventilation (VI), timing, and inspiratory upper-airway resistances (RUA). The
      results showed the following. 1) Compared with baseline, there was a significant
      increase in VI (158 +/- 11%, P < 0.05) during EH, but this was not accompanied by
      augmentation of VI during the successive hypoxia trials nor in VI during the
      recovery period (94.4 +/- 3.5%, P = not significant), indicating an absence of
      LTF. There was no change in inspiratory RUA during the trials. This is in
      contrast to our previous findings of respiratory plasticity in young adults
      during sleep. Sham studies did not show a change in any of the measured
      parameters. 2) We observed increased chemosensitivity with increased isocapnic
      hypoxic ventilatory response and hyperoxic suppression of VI in older vs. young
      adults during NREM sleep. Thus increased chemosensitivity, unconstrained by
      respiratory plasticity, may explain increased periodic breathing and central
      apneas in elderly adults during NREM sleep.

PMID- 26316511
TI  - Explained variance in the thermoregulatory responses to exercise: the independent
      roles of biophysical and fitness/fatness-related factors.
AB  - Individual variation in the thermoregulatory responses to exercise is notoriously
      large. Although aerobic fitness (Vo2 max) and body fatness are traditionally
      considered important predictors of individual core temperature and sweating
      responses, recent evidence indicates potentially important and independent roles
      for biophysical factors. Using stepwise regression, we examined the proportion of
      individual variability in rectal temperature changes (DeltaTre), whole body sweat
      loss (WBSL), and steady-state local sweat rate (LSRss) independently described by
      1) biophysical factors associated with metabolic heat production (Hprod) and
      evaporative heat balance requirements (Ereq) relative to body size and 2) factors
      independently related to Vo2 max and body fatness. In a total of 69 trials, 28
      males of wide-ranging morphological traits and Vo2 max values cycled at workloads
      corresponding to a range of absolute Hprod (410-898 W) and relative intensities
      (32.2-82.0% Vo2 max) for 60 min in 24.8 +/- 0.7 degrees C and 33.4 +/- 12.2%
      relative humidity. Hprod (in W/kg total body mass) alone described ~50% of the
      variability in DeltaTre (adjusted to r(2) = 0.496; P < 0.001), whereas surface
      area-to-mass ratio and body fat percentage (BF%) explained an additional 4.3 and
      2.3% of variability, respectively. For WBSL, Ereq (in W) alone explained ~71% of
      variance (adjusted to r(2) = 0.713, P < 0.001), and the inclusion of BF%
      explained an additional 1.3%. Similarly, Ereq (in W/m(2)) correlated
      significantly with LSRss (adjusted to r(2) = 0.603, P < 0.001), whereas %Vo2 max
      described an additional ~4% of total variance. In conclusion, biophysical
      parameters related to Hprod, Ereq, and body size explain 54-71% of the individual
      variability in DeltaTre, WBSL, and LSRss, and only 1-4% of additional variance is
      explained by factors related to fitness or fatness. 

PMID- 26316512
TI  - Assessment of regional ventilation and deformation using 4D-CT imaging for
      healthy human lungs during tidal breathing.
AB  - This study aims to assess regional ventilation, nonlinearity, and hysteresis of
      human lungs during dynamic breathing via image registration of four-dimensional
      computed tomography (4D-CT) scans. Six healthy adult humans were studied by
      spiral multidetector-row CT during controlled tidal breathing as well as during
      total lung capacity and functional residual capacity breath holds. Static images
      were utilized to contrast static vs. dynamic (deep vs. tidal) breathing. A
      rolling-seal piston system was employed to maintain consistent tidal breathing
      during 4D-CT spiral image acquisition, providing required between-breath
      consistency for physiologically meaningful reconstructed respiratory motion.
      Registration-derived variables including local air volume and anisotropic
      deformation index (ADI, an indicator of preferential deformation in response to
      local force) were employed to assess regional ventilation and lung deformation.
      Lobar distributions of air volume change during tidal breathing were correlated
      with those of deep breathing (R(2) ~ 0.84). Small discrepancies between tidal and
      deep breathing were shown to be likely due to different distributions of air
      volume change in the left and the right lungs. We also demonstrated an asymmetric
      characteristic of flow rate between inhalation and exhalation. With ADI, we were
      able to quantify nonlinearity and hysteresis of lung deformation that can only be
      captured in dynamic images. Nonlinearity quantified by ADI is greater during
      inhalation, and it is stronger in the lower lobes (P < 0.05). Lung hysteresis
      estimated by the difference of ADI between inhalation and exhalation is more
      significant in the right lungs than that in the left lungs.

PMID- 26316514
TI  - Digitization of Electrocardiogram From Telemetry Prior to In-hospital Cardiac
      Arrest: A Pilot Study.
AB  - BACKGROUND: Analyzing telemetry electrocardiogram (ECG) data over an extended
      period is often time-consuming because digital records are not widely available
      at hospitals. Investigating trends and patterns in the ECG data could lead to
      establishing predictors that would shorten response time to in-hospital cardiac
      arrest (I-HCA). This study was conducted to validate a novel method of digitizing
      paper ECG tracings from telemetry systems in order to facilitate the use of heart
      rate as a diagnostic feature prior to I-HCA. METHODS: This multicenter study used
      telemetry to investigate full-disclosure ECG papers of 44 cardiovascular patients
      obtained within 1 hr of I-HCA with initial rhythms of pulseless electrical
      activity and asystole. Digital ECGs were available for seven of these patients.
      An algorithm to digitize the full-disclosure ECG papers was developed using the
      shortest path method. The heart rate was measured manually (averaging R-R
      intervals) for ECG papers and automatically for digitized and digital ECGs.
      RESULTS: Significant correlations were found between manual and automated
      measurements of digitized ECGs (p < .001) and between digitized and digital ECGs
      (p < .001). Bland-Altman methods showed bias = .001 s, SD = .0276 s, lower and
      upper 95% limits of agreement for digitized and digital ECGs = .055 and -.053 s,
      and percentage error = 0.22%. Root mean square (rms), percentage rms difference,
      and signal to noise ratio values were in acceptable ranges. CONCLUSION: The
      digitization method was validated. Digitized ECG provides an efficient and
      accurate way of measuring heart rate over an extended period of time.

PMID- 26316515
TI  - Clinical efficacy and safety following dose tapering of ciclosporin in cats with
      hypersensitivity dermatitis.
AB  - Objectives This study was designed to evaluate the efficacy and safety of
      reducing ciclosporin (CsA) dosing frequency from daily to every other day (EOD)
      or twice a week (TW) according to clinical response in cats with hypersensitivity
      dermatitis (HD) and treated with CsA. Methods One hundred and ninety-one cats
      with HD were given 7 mg/kg CsA daily for at least 4 weeks. Depending on clinical
      response, the dosing frequency was tapered from daily to EOD over the next 4
      weeks and further to TW for an additional 4 weeks. Safety was evaluated through
      physical examinations, clinical pathology and the monitoring of adverse events
      (AEs). Results The majority of cats were able to have their dose of CsA tapered
      to either EOD (15.5%) or TW (62.9%) according to the clinical response. Observed
      AEs were most frequently mild and self-limiting vomiting and diarrhea. A higher
      percentage of AEs occurred with daily administration (73%) compared with other
      dosing regimens (27%). Conclusions and relevance Following 4 weeks of daily
      dosing at 7 mg/kg, CsA may be tapered to EOD or TW while maintaining the desired
      therapeutic response in cats with HD. Additionally, CsA appears to be well
      tolerated with fewer AEs at EOD or TW dosing. Establishing the lowest effective
      dosing frequency of CsA improves the drug's safety profile.

PMID- 26316513
TI  - Beneficial and detrimental role of adenosine signaling in diseases and therapy.
AB  - Adenosine is a major signaling nucleoside that orchestrates cellular and tissue
      adaptation under energy depletion and ischemic/hypoxic conditions by activation
      of four G protein-coupled receptors (GPCR). The regulation and generation of
      extracellular adenosine in response to stress are critical in tissue protection.
      Both mouse and human studies reported that extracellular adenosine signaling
      plays a beneficial role during acute states. However, prolonged excess
      extracellular adenosine is detrimental and contributes to the development and
      progression of various chronic diseases. In recent years, substantial progress
      has been made to understand the role of adenosine signaling in different
      conditions and to clarify its significance during the course of disease
      progression in various organs. These efforts have and will identify potential
      therapeutic possibilities for protection of tissue injury at acute stage by
      upregulation of adenosine signaling or attenuation of chronic disease progression
      by downregulation of adenosine signaling. This review is to summarize current
      progress and the importance of adenosine signaling in different disease stages
      and its potential therapeutic effects.

PMID- 26316516
TI  - Ultrasonographic, endoscopic and histological appearance of the caecum in
      clinically healthy cats.
AB  - Objectives The aim of the study was to describe the ultrasonographic and
      endoscopic appearance and characteristics of the caecum in asymptomatic cats, and
      to correlate these findings with histology. Methods Ex vivo ultrasonographic and
      histologic evaluations of a fresh caecum were initially performed. Then, 20
      asymptomatic cats, privately owned or originating from a reproductive colony,
      were recruited. All cats had an ultrasonographic examination of the
      ileocaecocolic junction, where the thickness of the caecal wall, ileocolic lymph
      nodes and the echogenicity of the local fat were assessed. They all underwent a
      colonoscopy with a macroscopic assessment of the mucosa and biopsies for
      histology. Results An ultrasonographic hypoechoic nodular inner layer, which
      corresponded to the coalescence of multiple lymphoid follicles originating from
      the submucosa and protruding in the mucosa on histology, was visible in all parts
      of the caecum. The combined mucosa and submucosa was measured
      ultrasonographically and defined as the follicular layer. Although all cats were
      asymptomatic, 3/19 cats showed mild caecal inflammation on histology. The most
      discriminatory ultrasonographic parameter in assessing this subclinical
      inflammation was the thickness of the follicular layer at the entrance of the
      caecum, with a cut-off value of 2.0 mm. All cats (20/20) showed some degree of
      macroscopic 'dimpling' of the caecal mucosa on endoscopy. Conclusions and
      relevance Lymphoid follicles in the caecal mucosa and submucosa constitute a
      unique follicular layer on ultrasound. In asymptomatic cats, a subtle, non
      clinically relevant inflammation may exist and this is correlated with an
      increased thickness of the follicular layer on ultrasound. On endoscopy, a
      'dimpled aspect' to the caecal mucosa is a normal finding in the asymptomatic
      cat.

PMID- 26316517
TI  - Effects of two concentrations of topical tropicamide on the Schirmer tear test in
      clinically normal cats.
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of topical
      tropicamide at two concentrations (0.5% and 1.0%) on the Schirmer tear test (STT)
      results in clinically normal cats. METHODS: Twenty-four adult domestic shorthair
      cats were randomly assigned to three groups. In all three groups, ophthalmic
      solutions were instilled in a randomly selected eye and the opposite eye served
      as the control. In groups 1, 2 and 3 one drop of 0.5% tropicamide, 1.0%
      tropicamide and distilled water was used, respectively. Tear production in both
      eyes was tested 30 and 60 mins after instillation in all three groups. RESULTS:
      Baseline mean +/- SEM STT values for the treated eyes in groups 1, 2 and 3 were
      13.37 +/- 2.91 mm/min, 10.87 +/- 1.39 mm/min and 11.37 +/- 1.65 mm/min,
      respectively. Thirty minutes after the drug instillation in the treated eye, mean
      +/- SEM STT values in groups 1, 2 and 3 were 4.87 +/- 3.05 mm/min, 2.00 +/- 0.84
      mm/min and 11.25 +/- 1.81 mm/min, respectively. The mean +/- SEM STT levels of
      the treated eye after 60 mins were 3.75 +/- 1.87 mm/min, 0.5 +/- 0.37 mm/min and
      11.42 +/- 1.78 mm/min in groups 1, 2 and 3, respectively. CONCLUSIONS AND
      RELEVANCE: Use of 0.5% topical tropicamide, instead of 1.0% tropicamide, as a
      mydriatic agent, can be recommended in cats. Tear production measurement should
      be performed prior to the administration of tropicamide, regardless of the
      concentration of this drug.

PMID- 26316519
TI  - Erratum.

PMID- 26316518
TI  - Direct Oral Anticoagulants for the Management of Thromboembolic Disorders: The
      Importance of Adherence and Persistence in Achieving Beneficial Outcomes.
AB  - Anticoagulation therapy is central to the management of thromboembolic disorders,
      and the use of direct oral anticoagulants offers several advantages over standard
      therapy with parenteral heparins and vitamin K antagonists. In phase III clinical
      trials, the direct oral anticoagulants (given once or twice daily) all
      demonstrated favorable benefit-risk profiles compared with conventional standard
      therapy for the treatment and secondary prevention of venous thromboembolism and
      for stroke prevention in patients with nonvalvular atrial fibrillation. In
      clinical practice, many factors may influence overall clinical outcomes in
      patients receiving anticoagulant therapy, including adherence and persistence to
      the prescribed therapy, which becomes particularly important during long-term
      therapy. When choosing an anticoagulant for an individual patient, the
      pharmacological and clinical profile of the anticoagulant, its dosing regimen,
      and the patient's clinical characteristics (eg, renal function and comorbidities)
      and preferences should be considered. This review examines the rationale for and
      clinical evidence of the selected dosing regimens of the direct oral
      anticoagulants for the treatment of venous thromboembolism and stroke prevention
      in nonvalvular atrial fibrillation. The potential influence of dosing strategies
      (eg, once- or twice-daily dosing) and other factors on patient adherence and
      therapy persistence are also discussed. 

PMID- 26316520
TI  - Symmetry breaking in the early mammalian embryo: the case for quantitative single
      cell imaging analysis.
AB  - In recent years, advances in imaging probes, cutting-edge microscopy techniques
      and powerful bioinformatics image analysis have markedly expanded the imaging
      toolbox available to developmental biologists. Apart from traditional qualitative
      studies, embryonic development can now be investigated in vivo with improved
      spatiotemporal resolution, with more detailed quantitative analyses down to the
      single-cell level of the developing embryo. Such imaging tools can provide many
      benefits to investigate the emergence of the asymmetry in the early mammalian
      embryo. Quantitative single-cell imaging has provided a deeper knowledge of the
      dynamic processes of how and why apparently indistinguishable cells adopt
      separate fates that ensure proper lineage allocation and segregation. To advance
      our understanding of the mechanisms governing such cell fate decisions, we will
      need to address current limitations of fluorescent probes, while at the same time
      take on challenges in image processing and analysis. New discoveries and
      developments in quantitative, single-cell imaging analysis will ultimately enable
      a truly comprehensive, multi-dimensional and multi-scale investigation of the
      dynamic morphogenetic processes that work in concert to shape the embryo. 

PMID- 26316521
TI  - The association of children's distress during venepuncture with parent and staff
      behaviours.
AB  - Venepuncture and other needle-related procedures can distress children and have a
      lasting negative impact. Adults' behaviour during these procedures may affect
      children's reactions. However, the literature is contradictory and rarely
      considers verbal and non-verbal behaviour together. This study therefore examined
      the effect of adults' verbal and non-verbal behaviour on children's distress
      during venepuncture. Participants comprised 51 child and carer dyads and 10 staff
      members. Child anxiety was measured before the procedure. The procedure was
      recorded. The resulting audio-visual data were coded using the Child-Adult
      Medical Procedure Interaction Scale-Revised. Correlation analysis identified
      variables that were significantly associated with child distress: child anxiety,
      carer distress-promoting behaviour, staff distress-promoting behaviour and
      intimate distance. These were included in a path diagram of child distress.
      Exploration of the diagram identified that children's anxiety was mostly strongly
      associated with children's distress during venepuncture. Staff and carer
      behaviour did not increase children's distress. The results suggest interventions
      to reduce children's distress during venepuncture may be more effective if they
      focus on reducing children's anxiety beforehand.

PMID- 26316522
TI  - Assessment of HIV Knowledge in Correctional Facility Health Care Workers: A Pilot
      Study of an Educational Intervention.
AB  - HIV rates are disproportionately higher in the incarcerated compared to the
      general population. Unfortunately, HIV sero-positive inmates report perceived
      discrimination and missed antiretroviral doses. Correctional facility nursing
      competency in HIV management may mitigate these concerns. Using validated
      knowledge instruments, the authors measured baseline HIV knowledge in
      correctional facility nurses from 3 correctional facilities in Alberta, Canada,
      and quantified changes after a targeted educational workshop. Basic HIV knowledge
      increased significantly, whereas perceived need for further HIV education
      significantly decreased postintervention. This study demonstrates that
      correctional facility nurses may not receive ideal HIV education during
      employment and that targeted HIV workshops can significantly increase knowledge
      and confidence when caring for affected individuals.

PMID- 26316523
TI  - Systemic Atherosclerotic Inflammation Following Acute Myocardial Infarction:
      Myocardial Infarction Begets Myocardial Infarction.
AB  - BACKGROUND: Preclinical data suggest that an acute inflammatory response
      following myocardial infarction (MI) accelerates systemic atherosclerosis. Using
      combined positron emission and computed tomography, we investigated whether this
      phenomenon occurs in humans. METHODS AND RESULTS: Overall, 40 patients with MI
      and 40 with stable angina underwent thoracic 18F-fluorodeoxyglucose combined
      positron emission and computed tomography scan. Radiotracer uptake was measured
      in aortic atheroma and nonvascular tissue (paraspinal muscle). In 1003 patients
      enrolled in the Global Registry of Acute Coronary Events, we assessed whether
      infarct size predicted early (<=30 days) and late (>30 days) recurrent coronary
      events. Compared with patients with stable angina, patients with MI had higher
      aortic 18F-fluorodeoxyglucose uptake (tissue-to-background ratio 2.15+/-0.30
      versus 1.84+/-0.18, P<0.0001) and plasma C-reactive protein concentrations (6.50
      [2.00 to 12.75] versus 2.00 [0.50 to 4.00] mg/dL, P=0.0005) despite having
      similar aortic (P=0.12) and less coronary (P=0.006) atherosclerotic burden and
      similar paraspinal muscular 18F-fluorodeoxyglucose uptake (P=0.52). Patients with
      ST-segment elevation MI had larger infarcts (peak plasma troponin 32 300 [10 200
      to >50 000] versus 3800 [1000 to 9200] ng/L, P<0.0001) and greater aortic 18F
      fluorodeoxyglucose uptake (2.24+/-0.32 versus 2.02+/-0.21, P=0.03) than those
      with non-ST-segment elevation MI. Peak plasma troponin concentrations correlated
      with aortic 18F-fluorodeoxyglucose uptake (r=0.43, P=0.01) and, on multivariate
      analysis, independently predicted early (tertile 3 versus tertile 1: relative
      risk 4.40 [95% CI 1.90 to 10.19], P=0.001), but not late, recurrent MI.
      CONCLUSIONS: The presence and extent of MI is associated with increased aortic
      atherosclerotic inflammation and early recurrent MI. This finding supports the
      hypothesis that acute MI exacerbates systemic atherosclerotic inflammation and
      remote plaque destabilization: MI begets MI. CLINICAL TRIAL REGISTRATION: URL:
      https://www.clinicaltrials.gov. Unique identifier: NCT01749254.

PMID- 26316524
TI  - Intracellular Na+ Concentration ([Na+]i) Is Elevated in Diabetic Hearts Due to
      Enhanced Na+-Glucose Cotransport.
AB  - BACKGROUND: Intracellular Na(+) concentration ([Na(+)]i) regulates Ca(2+)
      cycling, contractility, metabolism, and electrical stability of the heart.
      [Na(+)]i is elevated in heart failure, leading to arrhythmias and oxidative
      stress. We hypothesized that myocyte [Na(+)]i is also increased in type 2
      diabetes (T2D) due to enhanced activity of the Na(+)-glucose cotransporter.
      METHODS AND RESULTS: To test this hypothesis, we used myocardial tissue from
      humans with T2D and a rat model of late-onset T2D (HIP rat). Western blot
      analysis showed increased Na(+)-glucose cotransporter expression in failing
      hearts from T2D patients compared with nondiabetic persons (by 73+/-13%) and in
      HIP rat hearts versus wild-type (WT) littermates (by 61+/-8%). [Na(+)]i was
      elevated in HIP rat myocytes both at rest (14.7+/-0.9 versus 11.4+/-0.7 mmol/L in
      WT) and during electrical stimulation (17.3+/-0.8 versus 15.0+/-0.7 mmol/L);
      however, the Na(+)/K(+)-pump function was similar in HIP and WT cells, suggesting
      that higher [Na(+)]i is due to enhanced Na(+) entry in diabetic hearts. Indeed,
      Na(+) influx was significantly larger in myocytes from HIP versus WT rats (1.77+/
      0.11 versus 1.29+/-0.06 mmol/L per minute). Na(+)-glucose cotransporter
      inhibition with phlorizin or glucose-free solution greatly reduced Na(+) influx
      in HIP myocytes (to 1.20+/-0.16 mmol/L per minute), whereas it had no effect in
      WT cells. Phlorizin also significantly decreased glucose uptake in HIP myocytes
      (by 33+/-9%) but not in WT, indicating an increased reliance on the Na(+)-glucose
      cotransporter for glucose uptake in T2D hearts. CONCLUSIONS: Myocyte Na(+)
      glucose cotransport is enhanced in T2D, which increases Na(+) influx and causes
      Na(+) overload. Higher [Na(+)]i may contribute to arrhythmogenesis and oxidative
      stress in diabetic hearts.

PMID- 26316525
TI  - Prognostic Significance of Premature Atrial Complexes Burden in Prediction of
      Long-Term Outcome.
AB  - BACKGROUND: The prognostic significance of premature atrial complex (PAC) burden
      is not fully elucidated. We aimed to investigate the relationship between the
      burden of PACs and long-term outcome. METHODS AND RESULTS: We investigated the
      clinical characteristics of 5371 consecutive patients without atrial fibrillation
      (AF) or a permanent pacemaker (PPM) at baseline who underwent 24-hour
      electrocardiography monitoring between January 1, 2002, and December 31, 2004.
      Clinical event data were retrieved from the Bureau of National Health Insurance
      of Taiwan. During a mean follow-up duration of 10+/-1 years, there were 1209
      deaths, 1166 cardiovascular-related hospitalizations, 3104 hospitalizations for
      any reason, 418 cases of new-onset AF, and 132 PPM implantations. The optimal cut
      off of PAC burden for predicting mortality was 76 beats per day, with a
      sensitivity of 63.1% and a specificity of 63.5%. In multivariate analysis, a PAC
      burden >76 beats per day was an independent predictor of mortality (hazard ratio:
      1.384, 95% CI: 1.230 to 1.558), cardiovascular hospitalization (hazard ratio:
      1.284, 95% CI: 1.137 to 1.451), new-onset AF (hazard ratio: 1.757, 95% CI: 1.427
      to 2.163), and PPM implantation (hazard ratio: 2.821, 95% CI: 1.898 to 4.192).
      Patients with frequent PAC had increased risk of mortality attributable to
      myocardial infarction, heart failure, and sudden cardiac death. Frequent PACs
      increased risk of PPM implantation owing to sick sinus syndrome, high-degree
      atrioventricular block, and/or AF. CONCLUSIONS: The burden of PACs is
      independently associated with mortality, cardiovascular hospitalization, new
      onset AF, and PPM implantation in the long term.

PMID- 26316526
TI  - Executive Summary: 2015 Infectious Diseases Society of America (IDSA) Clinical
      Practice Guidelines for the Diagnosis and Treatment of Native Vertebral
      Osteomyelitis in Adults.
AB  - These guidelines are intended for use by infectious disease specialists,
      orthopedic surgeons, neurosurgeons, radiologists, and other healthcare
      professionals who care for patients with native vertebral osteomyelitis (NVO).
      They include evidence and opinion-based recommendations for the diagnosis and
      management of patients with NVO treated with antimicrobial therapy, with or
      without surgical intervention. 

PMID- 26316527
TI  - Photo quiz. Daptomycin-induced eosinophilic pneumonia.

PMID- 26316529
TI  - Physical Therapists, Telephone Coaches, and Patients With Knee Osteoarthritis:
      Qualitative Study About Working Together to Promote Exercise Adherence.
AB  - BACKGROUND: Integrated models of care are recommended for people with knee
      osteoarthritis (OA). Exercise is integral to management, yet exercise adherence
      is problematic. Telephone-based health coaching is an attractive adjunct to
      physical therapist-prescribed exercise that may improve adherence. Little is
      known about the perceptions and interpretations of physical therapists, telephone
      coaches, and patients engaged in this model of care. OBJECTIVES: The purpose of
      this study was to explore how stakeholders (physical therapists, telephone
      coaches, and patients) experienced, and made sense of, being involved in an
      integrated program of physical therapist-supervised exercise and telephone
      coaching for people with knee OA. DESIGN: A cross-sectional qualitative design
      drawing from symbolic interactionism was used. METHODS: Semistructured interviews
      with 10 physical therapists, 4 telephone coaches, and 6 patients with painful
      knee OA. Interviews were audiorecorded, transcribed, and analyzed using thematic
      analysis informed by grounded theory. RESULTS: Four themes emerged: (1) genuine
      interest and collaboration, (2) information and accountability, (3) program
      structure, and (4) roles and communication in teamwork. Patients reported they
      appreciated personalized, genuine interest from therapists and coaches and were
      aware of their complementary roles. A collaborative approach, with defined roles
      and communication strategies, was identified as important for effectiveness. All
      participants highlighted the importance of sharing information, monitoring, and
      being accountable to others. Coaches found the lack of face-to-face contact with
      patients hampered relationship building. Therapists and coaches referred to the
      importance of teamwork in delivering the intervention. LIMITATIONS: The small
      number of physical therapists and telephone coaches who delivered the
      intervention may have been biased toward favorable experiences with the
      intervention and may not be representative of their respective professions.
      CONCLUSIONS: Integrated physical therapy and telephone coaching was perceived as
      beneficial by most stakeholders. Programs should be structured but have some
      flexibility to give therapists and coaches some freedom to adjust treatment to
      individual patient needs as required. Opportunities for visual communication
      between telephone coaches and patients could facilitate relationship building.

PMID- 26316530
TI  - Perspectives on Active Video Gaming as a New Frontier in Accessible Physical
      Activity for Youth With Physical Disabilities.
AB  - This perspective article explores the utility of active video gaming as a means
      of reducing sedentary behavior and increasing physical activity among youth with
      physical disabilities and limitations in lower extremity function who typically
      are excluded from mainstream exercise options. Youth with physical disabilities
      are disproportionately affected by health problems that result from sedentary
      behavior, lack of physical activity, and low fitness levels. Physical,
      programmatic, and attitudinal barriers have a synergistic and compounded impact
      on youths' ability to participate in physical activity. A recent health and
      wellness task force recommendation from the American Physical Therapy
      Association's Section on Pediatrics supports analyzing individualized health
      behaviors and preferences that are designed to improve fitness, physical
      activity, and participation in pediatric rehabilitation. This recommendation
      represents an opportunity to explore nontraditional options to maximize
      effectiveness and sustainability of pediatric rehabilitation techniques for youth
      with disabilities who could best benefit from customized programming. One new
      frontier in promoting physical activity and addressing common physical activity
      barriers for youth with physical disabilities is active video games (AVGs), which
      have received growing attention as a promising strategy for promoting health and
      fitness in children with and without disabilities. The purpose of this article is
      to discuss the potential for AVGs as an accessible option to increase physical
      activity participation for youth with physical disabilities and limitations in
      lower extremity function. A conceptual model on the use of AVGs to increase
      physical activity participation for youth with physical disabilities is
      introduced, and future research potential is discussed, including a development
      project for game controller adaptations within the Rehabilitation Engineering
      Research Center on Interactive Exercise Technologies and Exercise Physiology for
      People With Disabilities (RERC RecTech) at the University of Alabama at
      Birmingham (UAB)/Lakeshore Foundation Research Collaborative. 

PMID- 26316531
TI  - Role of Health Services Research in Producing High-Value Rehabilitation Care.
AB  - The concept of value is receiving greater attention in rehabilitation and the
      broader health care environment. The overall purpose of this article is to
      present a framework to help clinicians, researchers, educators, and policy makers
      better understand the role of health services research in developing and
      evaluating evidence on value in rehabilitation. Value in health care is a
      multidimensional concept and may be defined differently by various stakeholders,
      but assessing value typically involves considering a combination of several
      health and economic outcomes. However, health care stakeholders often lack
      sufficient information on these outcomes to make well-informed decisions. Health
      services approaches such as comparative effectiveness research, patient-centered
      outcomes research, and health economics assessments are some ways to evaluate
      value. The evidence generated from such studies directly informs decision making
      and health policy. Rehabilitation professionals have a great opportunity to
      increase their engagement in describing, evaluating, delivering, and
      disseminating high-value care, but there are several barriers they need to
      consider to be most successful. Embracing health services research best practices
      is essential for advancing appropriate rehabilitation practice, research, and
      policy and for addressing challenges to implementing high-value care. 

PMID- 26316532
TI  - Use of Physical Therapy for Low Back Pain by Medicaid Enrollees.
AB  - BACKGROUND: Medicaid insures an increasing proportion of adults in the United
      States. Physical therapy use for low back pain (LBP) in this population has not
      been described. OBJECTIVE: The study objectives were: (1) to examine physical
      therapy use by Medicaid enrollees with new LBP consultations and (2) to evaluate
      associations with future health care use and LBP-related costs. DESIGN: The study
      was designed as a retrospective evaluation of claims data. METHODS: A total of
      2,289 patients with new LBP consultations were identified during 2012 (mean
      age=39.3 years [SD=11.9]; 68.2% women). The settings in which the patients
      entered care and comorbid conditions were identified. Data obtained at 1 year
      after entry were examined, and physical therapy use was categorized with regard
      to entry setting, early use (within 14 days of entry), or delayed use (>14 days
      after entry). The 1-year follow-up period was evaluated for use outcomes
      (imaging, injection, surgery, and emergency department visit) and LBP-related
      costs. Variables associated with physical therapy use and cost outcomes were
      evaluated with multivariate models. RESULTS: Physical therapy was used by 457
      patients (20.0%); 75 (3.3%) entered care in physical therapy, 89 (3.9%) received
      early physical therapy, and 298 (13.0%) received delayed physical therapy.
      Physical therapy was more common with chronic pain or obesity comorbidities and
      less likely with substance use disorders. Entering care in the emergency
      department decreased the likelihood of physical therapy. Entering care in
      physical medicine increased the likelihood. Relative to primary care entry,
      physical therapy entry was associated with lower 1-year costs. LIMITATIONS: A
      single state was studied. No patient-reported outcomes were included.
      CONCLUSIONS: Physical therapy was used often by Medicaid enrollees with LBP. High
      rates of comorbidities were evident and associated with physical therapy use.
      Although few patients entered care in physical therapy, this pattern may be
      useful for managing costs.

PMID- 26316533
TI  - Reliability of the ECHOWS Tool for Assessment of Patient Interviewing Skills.
AB  - BACKGROUND: History taking is an important component of patient/client
      management. Assessment of student history-taking competency can be achieved via a
      standardized tool. The ECHOWS tool has been shown to be valid with modest
      intrarater reliability in a previous study but did not demonstrate sufficient
      power to definitively prove its stability. OBJECTIVE: The purposes of this study
      were: (1) to assess the reliability of the ECHOWS tool for student assessment of
      patient interviewing skills and (2) to determine whether the tool discerns
      between novice and experienced skill levels. DESIGN: A reliability and construct
      validity assessment was conducted. METHODS: Three faculty members from the United
      States and Australia scored videotaped histories from standardized patients taken
      by students and experienced clinicians from each of these countries. The tapes
      were scored twice, 3 to 6 weeks apart. Reliability was assessed using interclass
      correlation coefficients (ICCs) and repeated measures. Analysis of variance
      models assessed the ability of the tool to discern between novice and experienced
      skill levels. RESULTS: The ECHOWS tool showed excellent intrarater reliability
      (ICC [3,1]=.74-.89) and good interrater reliability (ICC [2,1]=.55) as a whole.
      The summary of performance (S) section showed poor interrater reliability (ICC
      [2,1]=.27). There was no statistical difference in performance on the tool
      between novice and experienced clinicians. LIMITATIONS: A possible ceiling effect
      may occur when standardized patients are not coached to provide complex and
      obtuse responses to interviewer questions. Variation in familiarity with the
      ECHOWS tool and in use of the online training may have influenced scoring of the
      S section. CONCLUSION: The ECHOWS tool demonstrates excellent intrarater
      reliability and moderate interrater reliability. Sufficient training with the
      tool prior to student assessment is recommended. The S section must evolve in
      order to provide a more discerning measure of interviewing skills.

PMID- 26316534
TI  - Playskin Lift: Development and Initial Testing of an Exoskeletal Garment to
      Assist Upper Extremity Mobility and Function.
AB  - BACKGROUND: A person's ability to move his or her arms against gravity is
      important for independent performance of critical activities of daily living and
      for exploration that facilitates early cognitive, language, social, and
      perceptual-motor development. Children with a variety of diagnoses have
      difficulty moving their arms against gravity. OBJECTIVE: The purpose of this
      technical report is to detail the design process and initial testing of a novel
      exoskeletal garment, the Playskin Lift, that assists and encourages children to
      lift their arms against gravity. DESIGN: This report details the design theory
      and process, the device, and the results of field testing with a toddler with
      impaired upper extremity function due to arthrogryposis multiplex congenita.
      RESULTS: The Playskin Lift is an inexpensive (<$30 material costs), easy to use
      (5/5 rating), comfortable (5/5 rating), and attractive (4/5 rating) device. While
      wearing the device, the child was able to contact objects more often throughout
      an increased play space, to look at toys more while contacting them, and to
      perform more complex interactions with toys. LIMITATIONS: This report details
      initial testing with one child. Future testing with more participants is
      recommended. CONCLUSIONS: These results suggest that by considering the broad
      needs of users, including cost, accessibility, comfort, aesthetics, and function,
      we can design inexpensive devices that families and clinicians can potentially
      fabricate in their own communities to improve function, participation,
      exploration, and learning for children with disabilities.

PMID- 26316535
TI  - Modeling of the N-terminal Section and the Lumenal Loop of Trimeric Light
      Harvesting Complex II (LHCII) by Using EPR.
AB  - The major light harvesting complex II (LHCII) of green plants plays a key role in
      the absorption of sunlight, the regulation of photosynthesis, and in preventing
      photodamage by excess light. The latter two functions are thought to involve the
      lumenal loop and the N-terminal domain. Their structure and mobility in an
      aqueous environment are only partially known. Electron paramagnetic resonance
      (EPR) has been used to measure the structure of these hydrophilic protein domains
      in detergent-solubilized LHCII. A new technique is introduced to prepare LHCII
      trimers in which only one monomer is spin-labeled. These heterogeneous trimers
      allow to measure intra-molecular distances within one LHCII monomer in the
      context of a trimer by using double electron-electron resonance (DEER). These
      data together with data from electron spin echo envelope modulation (ESEEM)
      allowed to model the N-terminal protein section, which has not been resolved in
      current crystal structures, and the lumenal loop domain. The N-terminal domain
      covers only a restricted area above the superhelix in LHCII, which is consistent
      with the "Velcro" hypothesis to explain thylakoid grana stacking (Standfuss, J.,
      van Terwisscha Scheltinga, A. C., Lamborghini, M., and Kuhlbrandt, W. (2005) EMBO
      J. 24, 919-928). The conformation of the lumenal loop domain is surprisingly
      different between LHCII monomers and trimers but not between complexes with and
      without neoxanthin bound. 

PMID- 26316536
TI  - S-Nitrosylation Induces Both Autonomous Activation and Inhibition of
      Calcium/Calmodulin-dependent Protein Kinase II delta.
AB  - NO is known to modulate calcium handling and cellular signaling in the
      myocardium, but key targets for NO in the heart remain unidentified. Recent
      reports have implied that NO can activate calcium/calmodulin (Ca(2+)/CaM)
      dependent protein kinase II (CaMKII) in neurons and the heart. Here we use our
      novel sensor of CaMKII activation, Camui, to monitor changes in the conformation
      and activation of cardiac CaMKII (CaMKIIdelta) activity after treatment with the
      NO donor S-nitrosoglutathione (GSNO). We demonstrate that exposure to NO after
      Ca(2+)/CaM binding to CaMKIIdelta results in autonomous kinase activation, which
      is abolished by mutation of the Cys-290 site. However, exposure of CaMKIIdelta to
      GSNO prior to Ca(2+)/CaM exposure strongly suppresses kinase activation and
      conformational change by Ca(2+)/CaM. This NO-induced inhibition was ablated by
      mutation of the Cys-273 site. We found parallel effects of GSNO on
      CaM/CaMKIIdelta binding and CaMKIIdelta-dependent ryanodine receptor activation
      in adult cardiac myocytes. We conclude that NO can play a dual role in regulating
      cardiac CaMKIIdelta activity. 

PMID- 26316537
TI  - Host Cell-catalyzed S-Palmitoylation Mediates Golgi Targeting of the Legionella
      Ubiquitin Ligase GobX.
AB  - The facultative intracellular pathogen Legionella pneumophila, the causative
      agent of Legionnaires disease, infects and replicates within human alveolar
      macrophages. L. pneumophila delivers almost 300 effector proteins into the
      besieged host cell that alter signaling cascades and create conditions that favor
      intracellular bacterial survival. In order for the effectors to accomplish their
      intracellular mission, their activity needs to be specifically directed toward
      the correct host cell protein or target organelle. Here, we show that the L.
      pneumophila effector GobX possesses E3 ubiquitin ligase activity that is mediated
      by a central region homologous to mammalian U-box domains. Furthermore, we
      demonstrate that GobX exploits host cell S-palmitoylation to specifically
      localize to Golgi membranes. The hydrophobic palmitate moiety is covalently
      attached to a cysteine residue at position 175, which is part of an amphipathic
      alpha-helix within the C-terminal region of GobX. Site-directed mutagenesis of
      cysteine 175 or residues on the hydrophobic face of the amphipathic helix
      strongly attenuated palmitoylation and Golgi localization of GobX. Together, our
      study provides evidence that the L. pneumophila effector GobX exploits two post
      translational modification pathways of host cells, ubiquitination and S
      palmitoylation. 

PMID- 26316538
TI  - Psoriasis as an Independent Risk Factor for Cardiovascular Disease: An
      Epidemiologic Analysis Using a National Database.
AB  - BACKGROUND: Psoriasis is known to be associated with metabolic syndrome, a well
      established risk factor for ischemic heart disease and stroke. Emerging evidence
      indicates that psoriasis is an independent risk factor for cardiovascular disease
      and stroke. OBJECTIVE: To evaluate whether psoriasis is independently associated
      with myocardial infarction (MI), ischemic heart disease (MI, angina pectoris, or
      coronary heart disease), and stroke, we conducted a cross-sectional study using
      the US National Health and Nutrition Examination Survey (NHANES) database.
      METHODS: Data on clinical history of psoriasis, MI, angina pectoris, coronary
      heart disease, and stroke from the questionnaire as well as laboratory parameters
      on serum lipid and uric acid levels in the cycle years 2003-2006 and 2009-2012
      were analyzed. Multivariate analysis with logistic regression modelling was
      performed with the aforementioned cardiovascular events or stroke as the
      dependent variables and with risk factors such as age, gender, ethnic group,
      current smoking status, alcohol consumption, metabolic syndrome, hyperuricemia,
      and psoriasis as independent variables. RESULTS: There were 520 cases of
      psoriasis, and 108 of them had metabolic syndrome (20.8%). Well-established
      cardiovascular risk factors such as age, gender, ethnic group, smoking, alcohol
      consumption, metabolic syndrome, and hyperuricemia were also found to have
      significant associations with MI and ischemic heart disease (all P values <.001).
      Psoriatic patients were at significantly higher risks of developing MI (odds
      ratio [OR] 2.24; 95% CI: 1.27-3.95; P = .005) and ischemic heart disease (OR
      1.90; 95% CI: 1.18-3.05; P = .008), but not stroke (OR 1.01; 95% CI: 0.48-2.16; P
      = .744), after adjustment was made for major cardiovascular risk factors.
      CONCLUSION: This study provides epidemiological evidence that psoriasis may be
      independently associated with the development of MI and ischemic heart disease.
      Physicians should be cognizant of any underlying cardiovascular risk factors,
      especially among psoriatic patients with metabolic syndrome, and manage them
      according to national guidelines.

PMID- 26316539
TI  - Selectivity in the Use of Gi/o Proteins Is Determined by the DRF Motif in CXCR6
      and Is Cell-Type Specific.
AB  - CXCR6, the receptor for CXCL16, is expressed on multiple cell types and can be a
      coreceptor for human immunodeficiency virus 1. Except for CXCR6, all human
      chemokine receptors contain the D(3.49)R(3.50)Y(3.51) sequence, and all but two
      contain A(3.53) at the cytoplasmic terminus of the third transmembrane helix
      (H3C), a region within class A G protein-coupled receptors that contacts G
      proteins. In CXCR6, H3C contains D(3.49)R(3.50)F(3.51)I(3.52)V(3.53) at positions
      126-130. We investigated the importance and interdependence of the canonical D126
      and the noncanonical F128 and V130 in CXCR6 by mutating D126 to Y, F128 to Y, and
      V130 to A singly and in combination. For comparison, we mutated the analogous
      positions D142, Y144, and A146 to Y, F, and V, respectively, in CCR6, a related
      receptor containing the canonical sequences. Mutants were analyzed in both human
      embryonic kidney 293T and Jurkat E6-1 cells. Our data show that for CXCR6 and/or
      CCR6, mutations in H3C can affect both receptor signaling and chemokine binding;
      noncanonical H3C sequences are functionally linked, with dual changes mitigating
      the effects of single mutations; mutations in H3C that compromise receptor
      activity show selective defects in the use of individual Gi/o proteins; and the
      effects of mutations in H3C on receptor function and selectivity in Gi/o protein
      use can be cell-type specific. Our findings indicate that the ability of CXCR6 to
      make promiscuous use of the available Gi/o proteins is exquisitely dependent on
      sequences within the H3C and suggest that the native sequence allows for
      preservation of this function across different cellular environments. 

PMID- 26316541
TI  - Statistical process control and interrupted time series: a golden opportunity for
      impact evaluation in quality improvement.

PMID- 26316540
TI  - Structural Asymmetry of Phosphodiesterase-9A and a Unique Pocket for Selective
      Binding of a Potent Enantiomeric Inhibitor.
AB  - Phosphodiesterase-9 (PDE9) inhibitors have been studied as potential therapeutics
      for treatment of central nervous system diseases and diabetes. Here, we report
      the discovery of a new category of PDE9 inhibitors by rational design on the
      basis of the crystal structures. The best compound, (S)-6-((1-(4
      chlorophenyl)ethyl)amino)-1-cyclopentyl-1,5,6,7-tetrahydro-4H-pyrazolo[3,4
      day]pyrimidin-4-one [(S)-C33], has an IC50 value of 11 nM against PDE9 and the
      racemic C33 has bioavailability of 56.5% in the rat pharmacokinetic model. The
      crystal structures of PDE9 in the complex with racemic C33, (R)-C33, and (S)-C33
      reveal subtle conformational asymmetry of two M-loops in the PDE9 dimer and
      different conformations of two C33 enantiomers. The structures also identified a
      small hydrophobic pocket that interacts with the tyrosyl tail of (S)-C33 but not
      with (R)-C33, and is thus possibly useful for improvement of selectivity of PDE9
      inhibitors. The asymmetry of the M-loop and the different interactions of the C33
      enantiomers imply the necessity to consider the whole PDE9 dimer in the design of
      inhibitors. 

PMID- 26316542
TI  - A 20-Year Comparison of Football-Related Injuries in American and Canadian Youth
      Aged 6 to 17 Years: A Replication Study.
AB  - Introduction Little is known about Canadian youth football injuries. The
      objectives of this study were (a) to contrast the injuries in Canadian and
      American football players aged 6 to 17 years and (b) compare the injuries
      sustained during organized football with those in nonorganized football. Methods
      Using a retrospective cohort design based on data from the Canadian Hospitals
      Injury Reporting and Prevention Program and the National Electronic Injury
      Surveillance System a comparison of injuries was made. Results Trends in injuries
      were comparable. Proportions and odds of injuries were similar, except for a few
      exceptions. In Canada, more girls were injured and fractures were more prevalent.
      Compared with nonorganized football, organized football players were older,
      involved more males, and suffered more traumatic brain injuries and injuries to
      their lower extremities. Conclusion Canadian and American youth football injuries
      were similar. The type of football, be it organized or nonorganized, has an
      impact on injuries. 

PMID- 26316543
TI  - Synergistic effect of crude oil plus dispersant on bacterial community in a
      louisiana salt marsh sediment.
AB  - A combined effect of crude oil plus dispersant (Corexit 9500A) significantly
      altered indigenous bacterial communities in a Louisiana salt marsh sediment after
      30 days of incubation; the crude oil and/or Corexit 9500A treatments triggered
      shifts in bacterial communities and the shifted bacterial structure by crude oil
      plus Corexit 9500A was considerably different from those by either crude oil or
      Corexit 9500A. However, the synergistic effect of crude oil plus Corexit 9500A
      was not observed after 7 days of incubation; the bacterial community was slightly
      shifted by Corexit 9500A and the crude oil did not trigger any bacterial
      community shift after 7 days of incubation. DNA sequencing data indicated that
      Chromobacterium species was enriched in the Corexit 9500A microcosms after 7 days
      of incubation, while Pseudomonas, Advenella, Acidocella and Dyella spp. were
      enriched after 30 days of incubation. Parvibaculum was a dominant species in the
      crude oil microcosms after 30 days of incubation. Rhodanobacter, Dyella and
      Frateuria spp. were dominant in crude oil plus Corexit 9500A microcosms after 30
      days of incubation. Our data show that the effect of crude oil plus Corexit 9500A
      on bacterial community is synergistic, and thus the dispersant effect should be
      considered with the spilled oil to correctly evaluate the environmental impact. 

PMID- 26316544
TI  - Isolation and characterization of benzo[a]pyrene-degrading bacteria from the
      Tokyo Bay area and Tama River in Japan.
AB  - Benzo[a]pyrene (BaP) is one of the polycyclic aromatic hydrocarbons, and has
      serious detrimental effects on human health and aquatic environments. In this
      study, we isolated nine bacterial strains capable of degrading BaP from the Tokyo
      Bay area and Tama River in Japan. The isolated bacteria belonged to the phyla
      Actinobacteria, Firmicutes, Proteobacteria and Bacteroidetes, indicating that the
      BaP-degrading bacteria were widely present in the hydrosphere. ITB11, which
      shared 100% 16S rRNA identity with Mesoflavibacter zeaxanthinifaciens in the
      phylum Bacteroidetes, showed the highest degradation of BaP (approximately 86%)
      among the nine isolated strains after 42 days. Moreover, it was found that three
      of the nine isolated strains collectively removed 50-55% of BaP during the first
      7 days. Growth measurement of M. zeaxanthinifaciens revealed that the strain
      utilized BaP as a sole carbon and energy source and salicylate acted only as an
      inducer of BaP degradation. 

PMID- 26316545
TI  - Identification of an integron containing the quinolone resistance gene qnrA1 in
      Shewanella xiamenensis.
AB  - This study investigated multidrug resistance in Shewanella xiamenensis isolated
      from an estuarine water sample in China during 2014. This strain displayed
      resistance or decreased susceptibility to ampicillin, aztreonam, cefepime,
      cefotaxime, chloramphenicol, ciprofloxacin, erythromycin, kanamycin and
      trimethoprim-sulfamethoxazole. The antimicrobial resistance genes aacA3, blaOXA
      199, qnrA1 and sul1 were identified by PCR amplification and by sequencing.
      Pulsed-field gel electrophoresis and DNA hybridization experiments showed that
      the quinolone resistance gene qnrA1 was chromosomally located. qnrA1 was located
      in a complex class 1 integron, downstream from an ISCR1, and bracketed by two
      copies of qacEDelta1-sul1 genes. This integron is similar to In825 with four gene
      cassettes aacA3, catB11c, dfrA1z and aadA2az. An IS26-mel-mph2-IS26 structure was
      also detected in the flanking sequences, conferring resistance to macrolides.
      This is the first identification of the class 1 integron in S. xiamenensis. This
      is also the first identification of the qnrA1 gene and IS26-mediated macrolide
      resistance genes in S. xiamenensis. Presence of a variety of resistance genetic
      determinants in environmental S. xiamenensis suggests the possibility that this
      species may serve as a potential vehicle of antimicrobial resistance genes in
      aquatic environments. 

PMID- 26316546
TI  - Analysis of preference for carbon source utilization among three strains of
      aromatic compounds degrading Pseudomonas.
AB  - Soil isolates Pseudomonas putida CSV86, Pseudomonas aeruginosa PP4 and
      Pseudomonas sp. C5pp degrade naphthalene, phthalate isomers and carbaryl,
      respectively. Strain CSV86 displayed a diauxic growth pattern on phenylpropanoid
      compounds (veratraldehyde, ferulic acid, vanillin or vanillic acid) plus glucose
      with a distinct second lag-phase. The glucose concentration in the medium
      remained constant with higher cell respiration rates on aromatics and maximum
      protocatechuate 3,4-dioxygenase activity in the first log-phase, which gradually
      decreased in the second log-phase with concomitant depletion of the glucose. In
      strains PP4 and C5pp, growth profile and metabolic studies suggest that glucose
      is utilized in the first log-phase with the repression of utilization of
      aromatics (phthalate or carbaryl). All three strains utilize benzoate via the
      catechol 'ortho' ring-cleavage pathway. On benzoate plus glucose, strain CSV86
      showed preference for benzoate over glucose in contrast to strains PP4 and C5pp.
      Additionally, organic acids like succinate were preferred over aromatics in
      strains PP4 and C5pp, whereas strain CSV86 co-metabolizes them. Preferential
      utilization of aromatics over glucose and co-metabolism of organic acids and
      aromatics are found to be unique properties of P. putida CSV86 as compared with
      strains PP4 and C5pp and this property of strain CSV86 can be exploited for
      effective bioremediation. 

PMID- 26316547
TI  - Genetic evidence that the degradation of para-cresol by Geobacter metallireducens
      is catalyzed by the periplasmic para-cresol methylhydroxylase.
AB  - Two pathways for para-cresol (p-cresol) degradation by anaerobic bacteria have
      been elucidated; one involves fumarate addition at the methyl group of p-cresol
      by a hydroxylbenzylsuccinate synthase protein while the other utilizes a
      methylhydroxylase protein (PCMH) to catalyze hydroxylation of the methyl group of
      p-cresol. In Geobacter metallireducens, in vitro enzymatic assays showed that p
      cresol is degraded via the methylhydroxylation pathway. However, prior to this
      study these results had not been confirmed by genetic analyses. In this work, the
      gene coding for benzylsuccinate-CoA dehydrogenase (bbsG), an enzyme required for
      toluene degradation by G. metallireducens that is homologous to the p
      hydroxybenzylsuccinyl-CoA dehydrogenase involved in p-cresol degradation by
      Desulfobacula toluolica Tol2 via fumarate addition, and the gene encoding the
      alpha prime subunit of PCMH (pcmI), were deleted to investigate the possibility
      of co-existing p-cresol degradation pathways in G. metallireducens. The absence
      of a functional PcmI protein completely inhibited p-cresol degradation, while
      deletion of the bbsG gene had little impact. These results further support the
      observation that G. metallireducens utilizes a PCMH-initiated pathway for p
      cresol degradation. 

PMID- 26316548
TI  - Plasmid-encoded genes influence exosporium assembly and morphology in Bacillus
      megaterium QM B1551 spores.
AB  - Spores of Bacillus megaterium QM B1551 are encased in a morphologically
      distinctive exosporium. We demonstrate here that genes encoded on the indigenous
      pBM500 and pBM600 plasmids are required for exosporium assembly and or stability
      in spores of this strain. Bioinformatic analyses identified genes encoding
      orthologues of the B. cereus-family exosporium nap and basal layer proteins
      within the B. megaterium genome. Transcriptional analyses, supported by electron
      and fluorescent microscopy, indicate that the pole-localized nap, identified here
      for the first time in B. megaterium QM B1551 spores, is comprised of the BclA1
      protein. The role of the BxpB protein, which forms the basal layer of the
      exosporium in B. cereus spores, is less clear since spores of a null mutant
      strain display an apparently normal morphology. Retention of the localized nap in
      bxpB null spores suggests that B. megaterium employs an alternative mechanism to
      that used by B. cereus spores in anchoring the nap to the spore surface. 

PMID- 26316549
TI  - Morphological and molecular effects of cortisol and ACTH on zebrafish stage I and
      II follicles.
AB  - Oogenesis in zebrafish (Danio rerio) is controlled by the hypothalamus-pituitary
      gonadal axis and reproductive hormones. In addition, an interference of stress
      hormones is known with reproductive biology. In the presented work, we aimed to
      explore the hypothesis that cortisol (Cort) and ACTH may affect early oogenesis
      in zebrafish, given the presence of the specific receptors for glucocorticoids
      and ACTH in the zebrafish ovary. Follicles at stages I and II were exposed in
      vitro to 1  MUM Cort and ACTH for 48 h, then ultrastructural and molecular
      effects were analyzed. The comet assay demonstrated increased tail moments for
      Cort and ACTH treatment indicative of DNA damage. The mRNA expression of
      apoptotic genes (bax, bcl-2) was not altered by both treatments, but Cort
      increased significantly the expression of the ACTH receptor (mc2r). Cort
      stimulated the presence of the endoplasmic reticulum, predominantly at stage II,
      while ACTH induced a strong vacuolization. Viability of oocytes was not affected
      by both treatments and fluorescent staining (monodansylcadaverine/acridine
      orange) indicated a reduced quantity of autophagosomes for ACTH, and lower
      presence of nucleic acids in ooplasm for Cort and ACTH. Concluding, different
      responses were observed for stress hormones on early stages of zebrafish oocytes,
      which suggest a role for both hormones in the stress-mediated adverse effects on
      female gametogenesis.

PMID- 26316550
TI  - Chemokine CCL24 promotes the growth and invasiveness of trophoblasts through
      ERK1/2 and PI3K signaling pathways in human early pregnancy.
AB  - Chemokine CCL24, acting through receptor CCR3, is a potent chemoattractant for
      eosinophil in allergic diseases and parasitic infections. We recently reported
      that CCL24 and CCR3 are co-expressed by trophoblasts in human early pregnant
      uterus. Here we prove with evidence that steroid hormones estradiol (E),
      progesterone (P), and human chorionic gonadotropin (hCG), as well as decidual
      stromal cells (DSCs) could regulate the expression of CCL24 and CCR3 of
      trophoblasts. We further investigate how trophoblast-derived CCL24 mediates the
      function of trophoblasts in vitro, and conclude that CCL24/CCR3 promotes the
      proliferation, viability and invasiveness of trophoblasts. In addition, analysis
      of the downstream signaling pathways of CCL24/CCR3 show that extracellular signal
      regulated kinases (ERK1/2) and phosphoinositide 3-kinase (PI3K) pathways may
      contribute to the proliferation, viability and invasiveness of trophoblasts by
      activating intracellular molecules Ki67 and matrix metallopeptidase 9 (MMP9).
      However, we did not observe any inhibitory effect on trophoblasts when blocking c
      Jun N-terminal kinase (JNK) or p38 pathways. In conclusion, our data suggests
      that trophoblast-derived CCL24 at the maternal-fetal interface promotes
      trophoblasts cell growth and invasiveness by ERK1/2 and PI3K pathways. Meanwhile,
      pregnancy-related hormones (P and hCG), as well as DSCs could up-regulate
      CCL24/CCR3 expression in trophoblasts, which may indirectly influence the
      biological functions of trophoblasts. Thus, our results provide a possible
      explanation for the growth and invasion of trophoblasts in human embryo
      implantation. 

PMID- 26316551
TI  - Effects of modified sit-to-stand training on balance control in hemiplegic stroke
      patients: a randomized controlled trial.
AB  - OBJECTIVE: To explore the effectiveness of modified sit-to-stand training on
      balance function in hemiplegic stroke patients. DESIGN: Randomized controlled
      trial. SETTING: Rehabilitation medical centre. PARTICIPANTS: A total of 50
      hemiplegic patients with stroke were randomly assigned to the control and
      experimental groups (n = 25 for each group). INTERVENTIONS: Patients in the
      control group received the sit-to-stand training with symmetrical foot position,
      while patients in the experimental group were given the modified sit-to-stand
      training in which the paretic foot placed posterior. Subjects in both groups
      received 30 minutes of sit-to-stand training, five times a week, for four weeks.
      MAIN OUTCOME MEASURES: The time and weight-bearing distribution during sit-to
      stand movement, the centre of pressure sway length during quiet standing, the
      centre of pressure sway areas during dynamic standing and Berg Balance Scale were
      assessed before and after completing the four-week sit-to-stand training.
      RESULTS: Our data showed significant improvements in standing balance and the sit
      to-stand movement for two groups in the post-training compared with the pre
      training. After training, the rise time shortened more significantly in the
      experimental group (mean change, 0.90 +/-0.25 seconds) than the control group
      (mean change, 0.42 +/-0.18 seconds). Weight-bearing asymmetry showed
      significantly greater improvement in the experimental group (mean change, 0.17 +/
      0.10) than in the control group (mean change, 0.06 +/-0.05). Centre of pressure
      sway length was significantly smaller in the experimental group (mean change,
      27.85 +/-10.58 cm) than in the control group (mean change, 21.95 +/-8.19 cm).
      Centre of pressure sway areas was significantly larger in the experimental group
      (mean change, 84.24 +/-26.48 cm(2)) than in the control group (mean change, 67.74
      +/-22.84 cm(2)) (P = 0.027). The Berg Balance Scale was significantly higher in
      the experiment group (mean change, 8.4 +/-3.1) than the control group (mean
      change, 5.8+/-2.8). CONCLUSIONS: A modified sit-to-stand training improves the
      balance function in hemiplegic stroke patients.

PMID- 26316552
TI  - Group therapy task training versus individual task training during inpatient
      stroke rehabilitation: a randomised controlled trial.
AB  - OBJECTIVE: To compare the efficacy of intensive daily applied progressive group
      therapy task training with equally dosed individual progressive task training on
      self-reported mobility for patients with moderate to severe stroke during
      inpatient rehabilitation. DESIGN: Randomized controlled clinical trial. SETTING:
      In-patient rehabilitation center. SUBJECTS: A total of 73 subacute patients with
      stroke who were not able to walk without physical assistance at randomisation.
      INTERVENTIONS: Patients were allocated to group therapy task training (GT) or
      individual task training (IT). Both interventions were intended to improve
      walking competency and comprised 30 sessions of 90 minutes over six weeks. MAIN
      MEASURES: Primary outcome was the mobility domain of the Stroke Impact Scale (SIS
      3.0). Secondary outcomes were the other domains of SIS-3.0, standing balance,
      gait speed, walking distance, stair climbing, fatigue, anxiety and depression.
      RESULTS: No adverse events were reported in either arm of the trial. There were
      no significant differences between groups for the SIS mobility domain at the end
      of the intervention (Z= -0.26, P = 0.79). No significant differences between
      groups were found in gait speed improvements (GT:0.38 +/-0.23; IT:0.26+/-0.35),
      any other gait related parameters, or in non-physical outcomes such as depression
      and fatigue. CONCLUSION: Inpatient group therapy task training for patients with
      moderate to severe stroke is safe and equally effective as a dose-matched
      individual task training therapy. Group therapy task training may be delivered as
      an alternative to individual therapy or as valuable adjunct to increase time
      spent in gait-related activities.

PMID- 26316553
TI  - The effect of Kinesio taping application for acute non-specific low back pain: a
      randomized controlled clinical trial.
AB  - OBJECTIVE: To investigate the effect of Kinesio taping application in acute non
      specific low back pain. DESIGN: A randomized controlled clinical trial. SETTING:
      Physical Medicine and Rehabilitation Clinic. PARTICIPANTS: A total of 109
      patients with acute low back pain were randomized into either Kinesio taping (n =
      54) or control (n = 55) groups. INTERVENTION: The intervention group was treated
      with information and reassurance plus Kinesio taping, while the control group
      received merely information and reassurance. All participants were allowed to use
      as-needed doses of paracetamol. Kinesio tape was applied to the most painful area
      of the low back for a total of 12 days. MAIN OUTCOME MEASURES: Worst pain and
      disability were assessed at baseline, after the 12-day intervention, and at four
      weeks follow-up. During the first 12 days, participants filled in a pain diary
      consisting of a numeric rating scale and recorded the number of paracetamol
      tablets consumed daily. Disability was assessed with the Oswestry Disability
      Index. RESULTS: After 12 days of intervention, pain intensity and the Oswestry
      Disability Index improved significantly in both groups; the improvements were
      significantly superior in the Kinesio taping group (p = 0.003, p = 0.011). The
      Kinesio taping group reached pain control earlier (sixth day vs. 12th day) and
      consumed less paracetamol. At the fourth week, although pain intensity was
      significantly more reduced in the Kinesio taping group (p = 0.015), there were no
      differences with regard to disability. CONCLUSIONS: Kinesio taping provided
      significant improvements in pain and disability; thus, it can be used as a
      complementary method in acute non-specific low back pain.

PMID- 26316555
TI  - Psychosocial Correlates of AUDIT-C Hazardous Drinking Risk Status: Implications
      for Screening and Brief Intervention in College Settings.
AB  - The current study identified psychosocial variables associated with AUDIT-C
      hazardous drinking risk status for male and female college students. Logistic
      regression analysis revealed that AUDIT-C risk status was associated with alcohol
      related negative consequences, injunctive norms, and descriptive norms for both
      male and female participants. Sociability and self-perception outcome
      expectancies predicted risk status for females. Cognitive and behavioral
      impairment expectancies predicted risk status for men in the sample. Implications
      for screening and brief intervention programming efforts are discussed. 

PMID- 26316554
TI  - Global gene expression by Bacillus anthracis during growth in mammalian blood.
AB  - During the late stages of systemic anthrax, Bacillus anthracis grows rapidly in
      the host bloodstream. To identify potential genes necessary for this observed
      rapid growth, we defined the transcriptional profile of B. anthracis during in
      vitro growth in bovine blood. Genome-wide transcriptome analysis indicated that
      B. anthracis undergoes significant changes in its transcriptome profile during
      growth in blood, including the differential regulation of genes associated both
      with metabolism and known virulence factors. Collectively, these data provide a
      framework for future studies identifying specific B. anthracis factors required
      for growth in the mammalian bloodstream. 

PMID- 26316556
TI  - Telavancin for the treatment of methicillin-resistant Staphylococcus aureus
      infections.

PMID- 26316557
TI  - Telavancin: the long and winding road from discovery to food and drug
      administration approvals and future directions.
AB  - Telavancin (TD-6424) was discovered in 2000 and became the first marketed
      semisynthetic lipoglycopeptide in 2009. This parenteral antibacterial agent has a
      dual mechanism of action and potent in vitro activity against gram-positive
      pathogens, including methicillin-resistant Staphylococcus aureus and isolates
      with reduced vancomycin susceptibility. Pharmacokinetic and pharmacodynamic
      analyses support the concentration-dependent activity and once-daily dosing
      regimen of telavancin. A changing regulatory approval process, manufacturing
      obstacles, and the termination of a commercialization partnership have challenged
      the development and marketing of telavancin. The commercial operations for
      telavancin have been restored, a new manufacturer has been secured, and reliable
      product supplies are available for clinical use. In addition, telavancin
      continues to be supported by ongoing clinical research with the recent launch of
      the Telavancin Observational Use Registry (TOUR; NCT02288234) in the United
      States and an international phase 3, randomized trial comparing telavancin with
      standard therapy for the treatment of patients with complicated S. aureus
      bacteremia, including endocarditis (NCT02208063). 

PMID- 26316559
TI  - Telavancin: mechanisms of action, in vitro activity, and mechanisms of
      resistance.
AB  - Telavancin is a semisynthetic lipoglycopeptide derivative of vancomycin.
      Telavancin has a dual mechanism of antibacterial action, disrupting peptidoglycan
      synthesis and cell membrane function. In 2014, the Clinical and Laboratory
      Standards Institute (CLSI) revised the antimicrobial susceptibility testing
      method for telavancin, resulting in minimum inhibitory concentration (MIC)
      determinations that are more accurate and reproducible and demonstrate greater in
      vitro potency than shown with the previous testing method. The CLSI testing
      method changes coincided with revised telavancin MIC interpretive break point
      criteria for susceptibility approved by the US Food and Drug Administration for
      Staphylococcus aureus (<=0.12 ug/mL), Streptococcus pyogenes (<=0.12 ug/mL),
      Streptococcus agalactiae (<=0.12 ug/mL), Streptococcus anginosus group (<=0.06
      ug/mL), and Enterococcus faecalis (vancomycin susceptible, <=0.25 ug/mL).
      Telavancin is equally potent against methicillin-susceptible S. aureus (MSSA) and
      methicillin-resistant S. aureus (MRSA). It demonstrates activity against isolates
      of heterogeneous vancomycin-intermediate S. aureus and vancomycin-intermediate S.
      aureus but is poorly active against vancomycin-resistant S. aureus. It also
      demonstrates potent activity against Staphylococcus epidermidis and Streptococcus
      spp. (MIC90 <=0.03 ug/mL). Thus far, it has not been possible to select for high
      level telavancin resistance in the laboratory using serially passaged clinical
      isolates of MRSA and MSSA. 

PMID- 26316558
TI  - Evolving resistance among Gram-positive pathogens.
AB  - Antimicrobial therapy is a key component of modern medical practice and a
      cornerstone for the development of complex clinical interventions in critically
      ill patients. Unfortunately, the increasing problem of antimicrobial resistance
      is now recognized as a major public health threat jeopardizing the care of
      thousands of patients worldwide. Gram-positive pathogens exhibit an immense
      genetic repertoire to adapt and develop resistance to virtually all
      antimicrobials clinically available. As more molecules become available to treat
      resistant gram-positive infections, resistance emerges as an evolutionary
      response. Thus, antimicrobial resistance has to be envisaged as an evolving
      phenomenon that demands constant surveillance and continuous efforts to identify
      emerging mechanisms of resistance to optimize the use of antibiotics and create
      strategies to circumvent this problem. Here, we will provide a broad perspective
      on the clinical aspects of antibiotic resistance in relevant gram-positive
      pathogens with emphasis on the mechanistic strategies used by these organisms to
      avoid being killed by commonly used antimicrobial agents. 

PMID- 26316560
TI  - Skin and soft-tissue infections: a critical review and the role of telavancin in
      their treatment.
AB  - Skin and soft-tissue infections (SSTIs) are an important cause of morbidity and
      mortality among hospitalized patients and a major therapeutic challenge for
      clinicians. Although uncomplicated SSTIs are managed successfully on an
      outpatient basis, more serious infections extending to the subcutaneous tissue,
      fascia, or muscle require complex management. Early diagnosis, selection of
      appropriate antimicrobials, and timely surgical intervention are key to
      successful treatment. Surgical-site infections, an important category of SSTI,
      occur in approximately half a million patients in North America annually. SSTIs
      are also a potential source for life-threatening bacteremia and metastatic
      abscesses. Gram-positive organisms, such as Staphylococcus aureus and
      Streptococcus pyogenes, are the dominant organisms isolated early in the
      infectious process, whereas gram-negative organisms are found in chronic wounds.
      Methicillin-resistant S. aureus (MRSA) is a potential bloodstream invader that
      requires aggressive antimicrobial treatment and surgery. Recent concerns
      regarding vancomycin activity include heteroresistance in MRSA and increase in
      the minimum inhibitory concentrations (>1 or 2 ug/mL); however, alternative
      agents, such as telavancin, daptomycin, linezolid, ceftaroline, dalbavancin,
      oritavancin, and tedizolid, are now available for the treatment of severe MRSA
      infections. Here, we present a review of the epidemiology, etiology, and
      available treatment options for the management of SSTIs. 

PMID- 26316561
TI  - The role of telavancin in hospital-acquired pneumonia and ventilator-associated
      pneumonia.
AB  - Hospital-acquired pneumonia (HAP) due to gram-positive pathogens such as
      methicillin-resistant Staphylococcus aureus (MRSA) continues to be a major cause
      of morbid conditions and death. Telavancin is a lipoglycopeptide antibiotic with
      potent in vitro activity against a range of gram-positive pathogens, including
      MRSA, methicillin-susceptible S. aureus, and Streptococcus species. In 2 phase 3
      clinical trials, telavancin was noninferior to vancomycin in patients with HAP
      due to gram-positive pathogens. Clinically evaluable patients with S. aureus as
      the sole pathogen or S. aureus with a vancomycin minimum inhibitory concentration
      >1 ug/mL, however, had higher cure rates with telavancin than with vancomycin. In
      patients with bacteremic HAP, telavancin resulted in clearance of blood cultures.
      It was associated with increased serum creatinine levels and higher mortality
      rates in patients with moderate to severe renal impairment at baseline; however,
      on subsequent analysis, the outcomes seemed to have been at least partially
      affected by the adequacy of empiric gram-negative antimicrobial therapy. Thus,
      clinicians need to consider the risk-benefit balance when choosing telavancin in
      patients with severe renal impairment at baseline. Overall, these data support
      the use of telavancin in the treatment of HAP due to S. aureus, including MRSA
      and strains with elevated vancomycin minimum inhibitory concentrations, but
      clinicians should always weigh the risks and benefits of various treatment
      options. 

PMID- 26316562
TI  - Telavancin hospital-acquired pneumonia trials: impact of Gram-negative infections
      and inadequate Gram-negative coverage on clinical efficacy and all-cause
      mortality.
AB  - BACKGROUND: When hospital-acquired or ventilator-associated bacterial pneumonia
      (HABP/VABP) is caused by gram-positive and gram-negative pathogens or both (mixed
      infections), the adequacy of gram-negative coverage (GNC) can confound the
      assessment of a gram-positive agent under study. This analysis examines the
      influence of gram-negative infections and the adequacy of GNC on clinical
      efficacy and all-cause mortality in the telavancin HABP/VABP phase 3 ATTAIN
      trials (Assessment of Telavancin for Treatment of Hospital-Acquired Pneumonia).
      METHODS: This post hoc analysis evaluated 3 patient groups from ATTAIN: (1) gram
      positive-only infections, (2) gram-positive-only and mixed infections-adequate
      GNC, and (3) gram-negative-only infections and mixed infections with inadequate
      GNC. For each, clinical efficacy at test of cure and all-cause mortality at day
      28 were compared for telavancin and vancomycin. RESULTS/CONCLUSIONS: In the
      ATTAIN safety population there were 16 more deaths in the telavancin arms than in
      the vancomycin arms. Of these, 13 were in patients with gram-negative-only
      infections (n = 9) or with mixed infections and inadequate GNC (n = 4) and all
      had estimated baseline creatinine clearances of <30ml/min. Based on this
      analysis, clinical response and all-cause mortality could be confounded because
      there were more patients with gram-negative pathogens at baseline and more
      patients received inadequate treatment of these gram-negative infections in the
      telavancin groups.

PMID- 26316563
TI  - Changing Clinical and Therapeutic Trends in Tentorial Dural Arteriovenous
      Fistulas: A Systematic Review.
AB  - BACKGROUND AND PURPOSE: Tentorial dural arteriovenous fistulas are characterized
      by a high hemorrhagic risk. We evaluated trends in outcomes and management of
      tentorial dural arteriovenous fistulas and performed a meta-analysis evaluating
      clinical and angiographic outcomes by treatment technique. MATERIALS AND METHODS:
      We performed a comprehensive literature search for studies on surgical and
      endovascular treatment of tentorial dural arteriovenous fistulas. We compared the
      proportion of patients undergoing endovascular, surgical, and combined
      endovascular/surgical management; the proportion of patients presenting with
      ruptured tentorial dural arteriovenous fistulas; and proportion of patients with
      good neurologic outcome across 3 time periods: 1980-1995, 1996-2005, and 2006
      2014. We performed a random-effects meta-analysis, evaluating the rates of
      occlusion, long-term good neurologic outcome, perioperative morbidity, and
      resolution of symptoms for the 3 treatment modalities. RESULTS: Twenty-nine
      studies with 274 patients were included. The proportion of patients treated with
      surgical treatment alone decreased from 38.7% to 20.4% between 1980-1995 and 2006
      2014. The proportion of patients treated with endovascular therapy alone
      increased from 16.1% to 48.0%. The proportion of patients presenting with
      ruptured tentorial dural arteriovenous fistulas decreased from 64.4% to 43.6%.
      The rate of good neurologic outcome increased from 80.7% to 92.9%. Complete
      occlusion rates were highest for patients receiving multimodality treatment
      (84.0%; 95% CI, 72.0%-91.0%) and lowest for endovascular treatment (71.0%; 95%
      CI, 56.0%-83.0%; P < .01). Long-term good neurologic outcome was highest in the
      endovascular group (89.0%; 95% CI, 80.0%-95.0%) and lowest for the surgical group
      (73.0%; 95% CI, 51.0%-87.0%; P = .03). CONCLUSIONS: Patients with tentorial dural
      arteriovenous fistulas are increasingly presenting with unruptured lesions, being
      treated endovascularly, and experiencing higher rates of good neurologic
      outcomes. Endovascular treatment was associated with superior neurologic outcomes
      but lower occlusion rates.

PMID- 26316564
TI  - Detection of Nasopharyngeal Carcinoma by MR Imaging: Diagnostic Accuracy of MRI
      Compared with Endoscopy and Endoscopic Biopsy Based on Long-Term Follow-Up.
AB  - BACKGROUND AND PURPOSE: Our previous nasopharyngeal carcinoma detection study,
      comparing MR imaging, endoscopy, and endoscopic biopsy, showed that MR imaging is
      a highly sensitive test that identifies nasopharyngeal carcinomas missed by
      endoscopy. However, at the close of that study, patients without biopsy-proved
      nasopharyngeal carcinoma nevertheless had shown suspicious abnormalities on
      endoscopy and/or MR imaging. The aim of this study was to determine whether there
      were any patients with undiagnosed nasopharyngeal carcinoma by obtaining long
      term follow-up and to use these data to re-evaluate the diagnostic performance of
      MR imaging. MATERIALS AND METHODS: In the previous study, 246 patients referred
      to a hospital ear, nose, and throat clinic with suspected nasopharyngeal
      carcinoma, based on a wide range of clinical indications, had undergone MR
      imaging, endoscopy, and endoscopic biopsy, and 77 had biopsy-proved
      nasopharyngeal carcinoma. One hundred twenty-six of 169 patients without biopsy
      proved nasopharyngeal carcinoma underwent re-examination of the nasopharynx after
      a minimum of 3 years, including 17 patients in whom a previous examination (MR
      imaging = 11; endoscopy = 7) had been positive for nasopharyngeal carcinoma, but
      the biopsy had been negative for it. Patients with nasopharyngeal carcinoma were
      identified by biopsy obtained in the previous and this follow-up study; patients
      without nasopharyngeal carcinoma were identified by the absence of a tumor on re
      examination of the nasopharynx. The sensitivity and specificity of the previous
      investigations were updated and compared by using the Fisher exact test. RESULTS:
      One patient with a previous positive MR imaging finding was subsequently proved
      to have nasopharyngeal carcinoma. Nasopharyngeal carcinomas were not found in the
      remaining 125 patients at follow-up, and the previous positive findings for
      nasopharyngeal carcinoma on MR imaging and endoscopy were attributed to benign
      lymphoid hyperplasia. The diagnostic performances for the previous MR imaging,
      endoscopy, and endoscopic biopsy were 100%, 88%, and 94%, respectively, for
      sensitivity, and 92%, 94%, and 100%, respectively, for specificity; the
      differences between MR imaging and endoscopy were significant for sensitivity (P
      = .003) but not specificity (P = .617). CONCLUSIONS: MR imaging detected the 12%
      of nasopharyngeal carcinomas that were endoscopically invisible, including 1
      cancer that remained endoscopically occult for several years. Lymphoid
      hyperplasia reduced the specificity of MR imaging.

PMID- 26316565
TI  - Patterns of Tumor Contrast Enhancement Predict the Prognosis of Anaplastic
      Gliomas with IDH1 Mutation.
AB  - BACKGROUND AND PURPOSE: It is proposed that isocitrate dehydrogenase 1 (IDH1)
      mutation predicts the outcome in patients with high-grade glioma. In addition,
      contrast enhancement on preoperative MR imaging reflects tumor biologic features.
      Patients with anaplastic glioma with the IDH1 mutation were evaluated by using MR
      imaging to determine whether tumor enhancement is a prognostic factor and can be
      used to predict survival. MATERIALS AND METHODS: A cohort of 216 patients with
      histologically confirmed anaplastic glioma was reviewed retrospectively. Tumor
      contrast-enhancement patterns were classified on the basis of preoperative T1
      contrast MR images. Tumor IDH1 status was examined by using RNA sequencing. We
      used univariate analysis and the multivariate Cox model to evaluate the
      prognostic value of the IDH1 mutation and tumor contrast-enhancement pattern for
      progression-free survival and overall survival. RESULTS: In all 216 patients,
      IDH1 mutation was associated with longer progression-free survival (P = .004,
      hazard ratio = 0.439) and overall survival (P = .002, hazard ratio = 0.406). For
      patients with IDH1 mutant anaplastic glioma, the absence of contrast enhancement
      was associated with longer progression-free survival (P = .038, hazard ratio =
      0.473) and overall survival (P = .043, hazard ratio = 0.436). Furthermore, we
      were able to stratify the progression-free survival and overall survival of
      patients with IDH1 mutation by using the tumor contrast-enhancement patterns (P =
      .022 and 0.029, respectively; log-rank). CONCLUSIONS: Tumor enhancement on
      postcontrast MR imaging is a valuable prognostic factor for patients with
      anaplastic glioma and IDH1 mutation. Furthermore, the contrast-enhancement
      patterns could potentially be used to stratify the survival outcome of such
      patients.

PMID- 26316566
TI  - A New Aneurysm Occlusion Classification after the Impact of Flow Modification.
AB  - A new classification is proposed for cerebral aneurysms treated with any
      endovascular technique, for example, coiling with or without adjunctive devices,
      flow diversion, intrasaccular flow modifiers, or any combination of the above.
      Raymond-Roy Occlusion Classification is expanded with novel subgroups such as
      class 1 represents complete occlusion and is subdivided if a branch is integrated
      to, or originated from, the aneurysm sac; class 2 represents neck filling; class
      3 represents incomplete occlusion with aneurysm filling as in the previous
      classification; and class 4 describes the immediate postoperative status after
      extra- or intrasaccular flow modification treatment. A new concept, "stable
      remodeling," is included as class 5, which represents filling in the neck region
      that stays unchanged or reduced, as shown with at least 2 consecutive control
      angiographies, at least 6 months apart, for not <1 year, or the remodeled
      appearance of a dilated and/or tortuous vessel in continuation with the parent
      artery without sac filling. 

PMID- 26316567
TI  - Determinants of Intracranial Hemorrhage Occurrence and Outcome after
      Neurothrombectomy Therapy: Insights from the Solitaire FR With Intention For
      Thrombectomy Randomized Trial.
AB  - BACKGROUND AND PURPOSE: Intracranial hemorrhage is the most dreaded complication
      of neurothrombectomy therapy for acute ischemic stroke. The determinants of
      intracranial hemorrhage and its impact on clinical course remain incompletely
      delineated. The purpose of this study is to further investigate the clinical and
      procedural factors leading to intracranial hemorrhage and to define the clinical
      impact of different hemorrhagic subtypes. MATERIALS AND METHODS: We analyzed data
      prospectively collected in the Solitaire FR With Intention for Thrombectomy
      randomized clinical trial. A multivariable logistic regression model was used to
      identify independent clinical, imaging, and procedural predictors of any
      intracranial hemorrhage and of 7 intracranial hemorrhage subtypes. Univariate
      analysis was used to determine the impact of each of the intracranial hemorrhage
      subtypes on clinical outcome. RESULTS: Among the 144 enrolled patients, any
      radiologic intracranial hemorrhage (21.3% versus 38.2%, P = .035), symptomatic
      intracranial hemorrhage (1.1% versus 10.9%, P = .012), and subarachnoid
      hemorrhage (2.2% versus 12.7%, P = .027) occurred less frequently in the
      Solitaire FR than in the Merci retriever arms. The most common independent
      determinant of hemorrhage occurrence was rescue therapy with intra-arterial rtPA,
      which was associated with any intracranial hemorrhage and 4 subtypes and tended
      to be used more frequently in the Merci group (10.9% versus 3.4%; P = .09). Among
      the hemorrhage subtypes, basal ganglionic hemorrhage had the strongest impact on
      good clinical outcome at 90 days (OR, 0.30; P = .025) and was associated with
      higher reperfusion, prolonged time to treatment, and rescue therapy with intra
      arterial rtPA. CONCLUSIONS: Intracranial hemorrhage, especially subarachnoid and
      symptomatic intracerebral hemorrhage, occurs less frequently with the Solitaire
      FR than the Merci retriever, in part due to less frequent use of rescue therapy
      with intra-arterial rtPA. Basal ganglionic hemorrhage strongly affects clinical
      outcome and is distinctively related to late reperfusion.

PMID- 26316568
TI  - Brain Magnetic Susceptibility Changes in Patients with Natalizumab-Associated
      Progressive Multifocal Leukoencephalopathy.
AB  - We investigated the brain magnetic susceptibility changes induced by natalizumab
      associated progressive multifocal leukoencephalopathy. We retrospectively
      included 12 patients with natalizumab-progressive multifocal leukoencephalopathy,
      5 with progressive multifocal leukoencephalopathy from other causes, and 55
      patients with MS without progressive multifocal leukoencephalopathy for
      comparison. MR imaging examinations included T2* or SWI sequences in patients
      with progressive multifocal leukoencephalopathy (86 examinations) and SWI in all
      patients with MS without progressive multifocal leukoencephalopathy. Signal
      abnormalities on T2* and SWI were defined as low signal intensity within the
      cortex and/or U-fibers and the basal ganglia. We observed T2* or SWI signal
      abnormalities at the chronic stage in all patients with progressive multifocal
      leukoencephalopathy, whereas no area of low SWI signal intensity was detected in
      patients without progressive multifocal leukoencephalopathy. Among the 8 patients
      with asymptomatic natalizumab-progressive multifocal leukoencephalopathy,
      susceptibility changes were observed in 6 (75%). The basal ganglia adjacent to
      progressive multifocal leukoencephalopathy lesions systematically appeared
      hypointense by using T2* and/or SWI. Brain magnetic susceptibility changes may be
      explained by the increased iron deposition and constitute a useful tool for the
      diagnosis of progressive multifocal leukoencephalopathy. 

PMID- 26316569
TI  - Comparison of Inner Ear Contrast Enhancement among Patients with Unilateral Inner
      Ear Symptoms in MR Images Obtained 10 Minutes and 4 Hours after Gadolinium
      Injection.
AB  - BACKGROUND AND PURPOSE: Recently 4-hour delayed-enhanced 3D-FLAIR MR imaging has
      been used in pathophysiologic analysis of the inner ear in many auditory
      diseases, including sudden sensorineural hearing loss, but comparison among
      different time points is not clear in patients with unilateral inner ear
      symptoms. We compared the signal-intensity ratios of the inner ears in patients
      with unilateral inner ear symptoms on 10-minute delayed-enhanced and 4-hour
      delayed-enhanced 3D-FLAIR MR images after IV gadolinium injection. MATERIALS AND
      METHODS: The 10-minute delayed-enhanced and 4-hour delayed-enhanced 3D-FLAIR MR
      images were retrospectively analyzed. Signal-intensity ratios between the
      cerebellum and inner ear structures, such as the cochleae, vestibules, and
      vestibulocochlear nerve were assessed. Multiple comparisons were performed.
      RESULTS: Signal-intensity ratios of the affected cochleae, vestibules, and
      vestibulocochlear nerve were higher than those of unaffected sides in both 10
      minute delayed-enhanced and 4-hour delayed-enhanced images. At the affected side,
      signal-intensity ratios of the vestibulocochlear nerve were higher in patients
      with nonsudden sensorineural hearing loss than in those with sudden sensorineural
      hearing loss on both 10-minute delayed-enhanced and 4-hour delayed-enhanced
      images. The signal-intensity ratios of some affected inner ear structures were
      higher than those of the unaffected sides in a group of 30 patients with sudden
      sensorineural hearing loss and 20 patients with nonsudden sensorineural hearing
      loss on 10-minute delayed-enhanced and 4-hour delayed-enhanced images.
      CONCLUSIONS: Signal-intensity ratios of the inner ear show statistically
      significant increases in many diseases, especially neuritis, in 10-minute delayed
      enhanced and 4-hour delayed-enhanced images. The 4-hour delayed-enhanced images
      may be superior in neural inflammatory-dominant conditions, while 10-minute
      delayed-enhanced images may be superior in neural noninflammatory-dominant
      conditions.

PMID- 26316570
TI  - Susceptibility Vessel Sign on MRI Predicts Favorable Clinical Outcome in Patients
      with Anterior Circulation Acute Stroke Treated with Mechanical Thrombectomy.
AB  - BACKGROUND AND PURPOSE: The susceptibility vessel sign on MR imaging has been
      reported to indicate acute occlusion from erythrocyte-rich thrombus. The purpose
      of this study was to evaluate the influence of the susceptibility vessel sign
      seen on MR imaging before treatment on the clinical outcome after mechanical
      thrombectomy for anterior circulation acute stroke. MATERIALS AND METHODS: We
      retrospectively included 73 consecutive patients who were treated for anterior
      circulation acute stroke by mechanical thrombectomy from December 2009 to
      September 2013. Each patient underwent MR imaging before mechanical thrombectomy.
      The presence (susceptibility vessel sign+) or absence of the susceptibility
      vessel sign (susceptibility vessel sign-) was recorded. Mechanical thrombectomy
      was performed either alone or in association with IV tPA according to the site
      and time after occlusion. Good functional outcome was defined by an mRS <= 2 at 3
      months in susceptibility vessel sign+ and susceptibility vessel sign- groups.
      Patient clinical characteristics, initial NIHSS score and ASPECTS, site of
      occlusion, time between onset to groin puncture, TICI after mechanical
      thrombectomy, NIHSS score at day 1, and spontaneous hyperattenuation on CT at day
      1 were also analyzed. RESULTS: Fifty-three patients with susceptibility vessel
      sign+ and 20 with susceptibility vessel sign- were included in our study. mRS <=
      2 at 3 months occurred in 65% patients in the susceptibility vessel sign+ group
      and 26% in the susceptibility vessel sign- group (P = .004). On multivariate
      analysis, the susceptibility vessel sign was the only parameter before treatment
      that could predict mRS <= 2 at 3 months (OR, 8.7; 95% CI, 1.1-69.4; P = .04).
      CONCLUSIONS: Our study strongly suggests that the susceptibility vessel sign on
      MR imaging before treatment is predictive of favorable clinical outcome for
      patients presenting with anterior circulation acute stroke and treated with
      mechanical thrombectomy.

PMID- 26316571
TI  - Carotid Near-Occlusion: A Comprehensive Review, Part 1--Definition, Terminology,
      and Diagnosis.
AB  - Carotid near-occlusion is distal ICA luminal collapse beyond a tight stenosis,
      where the distal lumen should not be used for calculating percentage stenosis.
      Near-occlusion with full ICA collapse is well-known, with a threadlike lumen.
      However, near-occlusion without collapse is often subtle and can be overlooked as
      a usual severe stenosis. More than 10 different terms have been used to describe
      near-occlusion, sometimes causing confusion. This systematic review presents what
      is known about carotid near-occlusion. In this first part, the foci are
      definition, terminology, and diagnosis. 

PMID- 26316572
TI  - Association between transcription factor 7-like 2 rs7903146 polymorphism and
      diabetic retinopathy in type 2 diabetes mellitus: A meta-analysis.
AB  - As one of the vascular complications of type 2 diabetes mellitus, the incidence
      of diabetes retinopathy is greatly increasing worldwide. Both genetic and
      environmental factors are involved in the pathologies. A meta-analysis was
      conducted to assess the association between transcription factor 7-like 2
      polymorphism (rs7903146) and type 2 diabetic retinopathy. Published literature
      from PubMed, Web of Science and China National Knowledge Infrastructure were
      retrieved. Pooled odds ratios with 95% confidence intervals were calculated to
      estimate the strength of the association. Eight studies including 6422
      participants were included in the final meta-analysis. Our analysis provides
      substantial evidence that the rs7903146 variant is significantly associated with
      the risk of diabetic retinopathy in Caucasian populations while not in East Asian
      populations. The variant of rs7903146 appeared more likely to be a promising
      genetic biomarker of diabetic retinopathy in Caucasians. 

PMID- 26316573
TI  - Do different definitions modify the gender-specific associations of metabolic
      syndrome with cardiovascular risk factors?

PMID- 26316574
TI  - Metabolic syndrome: Different definitions and gender-specific associations with
      cardiovascular risk factors.

PMID- 26316575
TI  - ASAS40 and ASDAS clinical responses in the ABILITY-1 clinical trial translate to
      meaningful improvements in physical function, health-related quality of life and
      work productivity in patients with non-radiographic axial spondyloarthritis.
AB  - OBJECTIVE: To assess the impact of achieving Assessment in SpondyloArthritis
      international Society 40% (ASAS40) response or an Ankylosing Spondylitis Disease
      Activity Score inactive disease (ASDAS-ID) state on patient-reported outcomes
      (PROs) among patients with non-radiographic axial SpA (nr-axSpA). METHODS: Data
      are from ABILITY-1, a phase 3 trial of adalimumab vs placebo in nr-axSpA
      patients. PROs included the HAQ for Spondyloarthropathies (HAQ-S), 36-item Short
      Form Health Survey (SF-36) physical component summary (PCS) score and Work
      Productivity and Activity Impairment Questionnaire. Patients were grouped by
      clinical response using ASAS40 response and ASDAS disease states at week 12.
      Changes in PROs from baseline to week 12 were compared between groups using
      analysis of covariance with adjustment for baseline scores. RESULTS: At week 12,
      47 of 179 patients were ASAS40 responders and 26 of 176 patients achieved ASDAS
      ID (ASDAS <1.3). Compared with non-responders (n = 132), ASAS40 responders (n =
      47) had a significantly greater improvement in mean HAQ-S (-0.65 vs -0.05, P <
      0.0001), SF-36 PCS (12.4 vs 0.7, P < 0.0001), presenteeism (-24.7 vs -2.2, P <
      0.0001), overall work impairment (-23.9 vs -2.5, P < 0.0001) and activity
      impairment (-33.5 vs -0.9, P < 0.0001) at week 12. Similarly, ASDAS-ID, ASDAS
      clinically important improvement (ASDAS-CII; improvement >1.1) and major
      improvement (ASDAS-MI; improvement >2.0) were associated with significantly
      greater improvements from baseline in the majority of the PROs. CONCLUSION: Among
      nr-axSpA patients, ASAS40, ASDAS-CII and ASDAS-MI response and achievement of
      ASDAS-ID were associated with statistically significant and clinically meaningful
      improvements in physical function, health-related quality of life and work
      productivity in a higher percentage of patients.

PMID- 26316576
TI  - Ultrasound is a useful adjunct in diagnosis of eosinophilic fasciitis.

PMID- 26316577
TI  - Eculizumab as rescue therapy in severe resistant lupus nephritis.

PMID- 26316578
TI  - Are guidelines good value for money?

PMID- 26316579
TI  - Does disease activity add to functional disability in estimation of utility for
      rheumatoid arthritis patients on biologic treatment?
AB  - OBJECTIVE: Treatment in general is mostly directly aimed at disease activity, and
      measures such as the DAS28 might therefore present important additional
      information. Our aim was to develop and validate a model that uses a combination
      of disease activity (DAS28) and HAQs to estimate EuroQoL 5-dimension scale (EQ5D)
      utilities. METHODS: Longitudinal data from a cohort study in RA patients from the
      Utrecht Rheumatoid Arthritis Cohort study Group (Stichting Reumaonderzoek
      Utrecht) who started treatment with a biologic drug were used for mapping and
      validation. All 702 observations, including DAS28, HAQ and EQ5D assessed at the
      same time points, were used. The observations were randomly divided into a subset
      for development of the model (n = 428 observations) and a subset for validation
      (n = 274). A stepwise multivariable regression analysis was used to test the
      association of DAS28 (components) and HAQ (domains) with EQ5D. Model performance
      was assessed using the explained variance (R(2)) and root mean square errors.
      Observed and predicted utility scores were compared to check for under- or
      overestimation of the scores. Finally, the performance of the model was compared
      with published mapping models. RESULTS: Lower DAS28 score and HAQ items dressing
      and grooming, arising, eating, walking and activities were associated with higher
      EQ5D scores. The final model had an explained variance of 0.35 and a lower root
      mean square error as compared with other models tested. The agreement between
      predicted and observed scores was fair. CONCLUSION: HAQ components estimate EQ5D
      better than total HAQ. Adding DAS28 to HAQ components does not result in better
      utility estimations.

PMID- 26316580
TI  - Quantitative power Doppler ultrasound measures of peripheral joint synovitis in
      poor prognosis early rheumatoid arthritis predict radiographic progression.
AB  - OBJECTIVE: To assess the value of quantitative vascular imaging by power Doppler
      US (PDUS) as a tool that can be used to stratify patient risk of joint damage in
      early seropositive RA while still biologic naive but on synthetic DMARD
      treatment. METHODS: Eighty-five patients with seropositive RA of <3 years
      duration had clinical, laboratory and imaging assessments at 0 and 12 months.
      Imaging assessments consisted of radiographs of the hands and feet, two
      dimensional (2D) high-frequency and PDUS imaging of 10 MCP joints that were
      scored for erosions and vascularity and three-dimensional (3D) PDUS of MCP joints
      and wrists that were scored for vascularity. RESULTS: Severe deterioration on
      radiographs and ultrasonography was seen in 45 and 28% of patients, respectively.
      The 3D power Doppler volume and 2D vascularity scores were the most useful US
      predictors of deterioration. These variables were modelled in two equations that
      estimate structural damage over 12 months. The equations had a sensitivity of
      63.2% and specificity of 80.9% for predicting radiographic structural damage and
      a sensitivity of 54.2% and specificity of 96.7% for predicting structural damage
      on ultrasonography. CONCLUSION: In seropositive early RA, quantitative vascular
      imaging by PDUS has clinical utility in predicting which patients will derive
      benefit from early use of biologic therapy.

PMID- 26316581
TI  - Rituximab done: what's next in rheumatoid arthritis? A European observational
      longitudinal study assessing the effectiveness of biologics after rituximab
      treatment in rheumatoid arthritis.
AB  - OBJECTIVE: To compare the effectiveness of biologics after rituximab (RTX)
      treatment in RA. METHODS: The effectiveness of TNF-alpha inhibitors (TNFi),
      abatacept (ABA) or tocilizumab (TCZ) was examined in patients previously treated
      with RTX using clinical data collected in the Collaborative Registries for the
      Evaluation of Rituximab in RA Collaborative registry. Patients had stopped RTX 6
      months or less prior to the new biologic and had a baseline visit within 21 days
      of starting the new biologic. RESULTS: Two hundred and sixty-five patients were
      analysed after 6 months of treatment. Patients on TCZ (n = 86) had a greater
      decline of DAS28-ESR and clinical disease activity index than patients on TNFi (n
      = 89) or ABA (n = 90). This effect was also seen after adjusting for baseline
      prednisone use and the number of previous biologics. The mean DAS28-ESR scores in
      patients on TCZ were 1.0 (95% CI: 0.2, 1.7) and 1.8 (95% CI: 1.0, 2.5) points
      lower than in patients on TNFi or ABA, respectively. In patients on TCZ, the
      clinical disease activity index was 9.4 (95% CI: 1.7, 16.1) and 8.1 (95% CI: 0.9,
      15.3) points lower than on TNFi and ABA, respectively. Patients on TCZ more
      frequently had good EULAR responses than patients on TNFi or ABA (66 vs 31 vs
      14%, P < 0.001). The HAQ disability index improved in all treatment groups (P <
      0.001), but did not differ between biologics, as did drug retention rates. The
      reasons for discontinuation of RTX and the number of previous biologics had no
      influence on outcomes. CONCLUSION: In this observational cohort of patients who
      discontinued RTX, TCZ provided a better control of RA than ABA or TNFi.

PMID- 26316582
TI  - Elevated baseline power Doppler discriminates an RA subgroup highly responsive to
      therapy.

PMID- 26316583
TI  - How reliable are Functional Movement Screening scores? A systematic review of
      rater reliability.
AB  - BACKGROUND: Several physical assessment protocols to identify intrinsic risk
      factors for injury aetiology related to movement quality have been described. The
      Functional Movement Screen (FMS) is a standardised, field-expedient test battery
      intended to assess movement quality and has been used clinically in
      preparticipation screening and in sports injury research. AIM: To critically
      appraise and summarise research investigating the reliability of scores obtained
      using the FMS battery. STUDY DESIGN: Systematic literature review. METHODS:
      Systematic search of Google Scholar, Scopus (including ScienceDirect and PubMed),
      EBSCO (including Academic Search Complete, AMED, CINAHL, Health Source:
      Nursing/Academic Edition), MEDLINE and SPORTDiscus. Studies meeting eligibility
      criteria were assessed by 2 reviewers for risk of bias using the Quality
      Appraisal of Reliability Studies checklist. Overall quality of evidence was
      determined using van Tulder's levels of evidence approach. RESULTS: 12 studies
      were appraised. Overall, there was a 'moderate' level of evidence in favour of
      'acceptable' (intraclass correlation coefficient >=0.6) inter-rater and intra
      rater reliability for composite scores derived from live scoring. For inter-rater
      reliability of composite scores derived from video recordings there was
      'conflicting' evidence, and 'limited' evidence for intra-rater reliability. For
      inter-rater reliability based on live scoring of individual subtests there was
      'moderate' evidence of 'acceptable' reliability (kappa>=0.4) for 4 subtests (Deep
      Squat, Shoulder Mobility, Active Straight-leg Raise, Trunk Stability Push-up) and
      'conflicting' evidence for the remaining 3 (Hurdle Step, In-line Lunge, Rotary
      Stability). CONCLUSIONS: This review found 'moderate' evidence that raters can
      achieve acceptable levels of inter-rater and intra-rater reliability of composite
      FMS scores when using live ratings. Overall, there were few high-quality studies,
      and the quality of several studies was impacted by poor study reporting
      particularly in relation to rater blinding.

PMID- 26316584
TI  - Resveratrol attenuates renal injury and fibrosis by inhibiting transforming
      growth factor-beta pathway on matrix metalloproteinase 7.
AB  - Renal injury has a strong relationship to the subsequent development of renal
      fibrosis. In developing renal fibrosis, tubular epithelial cells in the kidney
      underwent epithelial-mesenchymal transition (EMT). Matrix metalloproteinase 7
      (MMP7) was reported to reduce E-cadherin and induce EMT by up-regulation of beta
      catenin/lymphoid enhancer-binding factor 1 (LEF1) signaling. In this research, we
      tried to evaluate the role of resveratrol (RSV) on EMT process in renal injury
      and fibrosis. Human tubular epithelial cell HK-2 cells were treated with
      aristolochic acid (AAs) and transforming growth factor-beta(TGF-beta) to induce
      EMT with or without the administration of RSV. The inhibitory role of RSV on EMT
      in renal injury and fibrosis was determined by Western blotting, real-time PCR,
      and immunofluorescence staining. The EMT repressing role of RSV was also
      evaluated in vivo by renal ischemia-reperfusion (I/R) injury and unilateral
      ureteral obstruction (UUO) models. The underlying mechanism was investigated by
      shRNA interfering MMP7 and sirtuin 1 (SIRT1) expression. The results indicated
      that RSV reversed human kidney 2 (HK-2) cell EMT, renal I/R injury, and renal
      fibrosis. MMP7 inhibition was responsible for RSV-induced EMT repression. SIRT1
      was up-regulated by RSV inhibited TGF-beta pathway on MMP7 via deacetylating
      Smad4. In conclusion, RSV attenuated renal injury and fibrosis by inhibiting EMT
      process which was attributed to the fact that the up-regulated SIRT1 by RSV
      deacetylated Smad4 and inhibited MMP7 expression. 

PMID- 26316585
TI  - The impact of acute aerobic exercise on chitinase 3-like protein 1 and intelectin
      1 expression in obesity.
AB  - Chitinase 3-like 1 (CHI3L1) and intelectin 1 (ITLN-1) recognize microbial N
      acetylglucosamine polymer and galactofuranosyl carbohydrates, respectively. Both
      lectins are highly abundant in plasma and seem to play pro- and anti-inflammatory
      roles, respectively, in obesity and inflammatory-related illnesses. The aim of
      this study was to examine whether plasma levels of these lectins in obese
      subjects are useful for monitoring inflammatory conditions immediately influenced
      by acute aerobic exercise. Plasma interleukin-6, a pro-inflammatory cytokine, was
      also examined. Twenty-two (11 obese and 11 normal-weight) healthy subjects, ages
      18-30 years, were recruited to perform a 30 min bout of acute aerobic exercise at
      75% VO2max. We confirmed higher baseline levels of plasma CHI3L1, but lower ITLN
      1, in obese subjects than in normal-weight subjects. The baseline levels of
      CHI3L1 were negatively correlated with cardiorespiratory fitness (relative
      VO2max). However, when controlled for BMI, the relationship between baseline
      level of CHI3L1 and relative VO2max was no longer observed. While acute aerobic
      exercise elicited an elevation in these parameters, we found a lower ITLN-1
      response in obese subjects compared to normal-weight subjects. Our study clearly
      indicates that acute aerobic exercise elicits a pro-inflammatory response (e.g.
      CHI3L1) with a lower anti-inflammatory effect (e.g. ITLN-1) in obese individuals.
      Furthermore, these lectins could be predictors of outcome of exercise
      interventions in obesity-associated inflammation. 

PMID- 26316586
TI  - Upregulation of microRNA-370 facilitates the repair of amputated fingers through
      targeting forkhead box protein O1.
AB  - Angiogenesis is critical to the success of digital replantation. Recent study
      suggests an important regulatory role of microRNA-370 (miR-370) in ischemia
      reperfusion injury. However, its function in digital replantation is poorly
      understood. In this study, we reported that the expression of miR-370 was
      upregulated in replantation tissues. miR-370 mimic transfection promoted human
      umbilical vein endothelial cells (HUVECs) proliferation by regulating the cell
      cycle and inhibited apoptosis. miR-370 mimic transfection also significantly
      increased HUVECs migration and induced the formation of capillary-like structures
      in HUVECs, indicated that miR-370 promoted capillary tube formation in vitro.
      Furthermore, forkhead box protein O1 (FOXO1) was identified as the functional
      target of miR-370 by dual-luciferase reporter assay. FOXO1 overexpression vector
      lacked 3'-UTR together with miR-370 mimic transfection strongly abrogated miR-370
      induced cell proliferation and the formation of capillary-like structures in
      HUVECs. Taken together, our results revealed that the upregulation of miR-370
      might facilitate the repair of amputated fingers by regulating angiogenesis
      through targeting FOXO1. This study provided a potential therapeutic target for
      the restoration of finger function after replantation. 

PMID- 26316588
TI  - Plasma miR-185 is decreased in patients with esophageal squamous cell carcinoma
      and might suppress tumor migration and invasion by targeting RAGE.
AB  - The receptor for advanced-glycation end products (RAGE) is upregulated in various
      cancers and has been associated with tumor progression, but little is known about
      its expression and regulation by microRNAs (miRNAs) in esophageal squamous cell
      carcinoma (ESCC). Here, we describe miR-185, which represses RAGE expression, and
      investigate the biological role of miR-185 in ESCC. In this study, we found that
      the high level of RAGE expression in 29 pairs of paraffin-embedded ESCC tissues
      was correlated positively with the depth of invasion by immunohistochemistry,
      suggesting that RAGE was involved in ESCC. We used bioinformatics searches and
      luciferase reporter assays to investigate the prediction that RAGE was regulated
      directly by miR-185. Besides, overexpression of miR-185 in ESCC cells was
      accompanied by 27% (TE-11) and 49% (Eca-109) reduced RAGE expression. The effect
      was further confirmed in RAGE protein by immunofluorescence in both cell lines.
      The effects were reversed following cotransfection with miR-185 and high-level
      expression of the RAGE vector. Furthermore, the biological role of miR-185 in
      ESCC cell lines was investigated using assays of cell viability, Ki-67 staining,
      and cell migration and invasion, as well as in a xenograft model. We found that
      overexpression of miR-185 inhibited migration and invasion by ESCC cells in vitro
      and reduced their capacity to develop distal pulmonary metastases in vivo partly
      through the RAGE/heat shock protein 27 pathway. Interestingly, in clinical
      specimens, the level of plasma miR-185 expression was decreased significantly (P
      = 0.002) in patients with ESCC [0.500; 95% confidence interval (CI) 0.248-1.676]
      compared with healthy controls (2.410; 95% CI 0.612-5.671). The value of the area
      under the receiver-operating characteristic curve was 0.73 (95% CI 0.604-0.855).
      In conclusion, our findings shed novel light on the role of miR-185/RAGE in ESCC
      metastasis, and plasma miR-185 has potential as a novel diagnostic biomarker in
      ESCC.

PMID- 26316587
TI  - Mesenchymal stromal cell therapy in liver disease: opportunities and lessons to
      be learnt?
AB  - End-stage liver disease is responsible for 30,000 deaths per year in the United
      States alone, and it is continuing to increase every year. With liver
      transplantation the only curative treatment currently available, new therapies
      are in great demand. Mesenchymal stem cells (MSC) offer an opportunity to both
      treat liver inflammatory damage, as well as reverse some of the changes that
      occur following chronic liver injury. With the ability to regulate both the
      innate and adaptive immune system, as well as both inhibit and promote apoptosis
      of effector inflammatory cells, there are numerous therapeutic opportunities for
      MSC in acute and chronic liver disease. This article critically appraises the
      potential therapeutic roles of MSC in liver disease, as well as the barriers to
      their adoption into clinical practice.

PMID- 26316589
TI  - Effect of dietary fructose on portal and systemic serum fructose levels in rats
      and in KHK-/- and GLUT5-/- mice.
AB  - Elevated blood fructose concentrations constitute the basis for organ dysfunction
      in fructose-induced metabolic syndrome. We hypothesized that diet-induced changes
      in blood fructose concentrations are regulated by ketohexokinase (KHK) and the
      fructose transporter GLUT5. Portal and systemic fructose concentrations
      determined by HPLC in wild-type mice fed for 7 days 0% free fructose were <0.07
      mM, were independent of time after feeding, were similar to those of GLUT5(-/-),
      and did not lead to hyperglycemia. Postprandial fructose levels, however,
      increased markedly in those fed isocaloric 20% fructose, causing significant
      hyperglycemia. Deletion of KHK prevented fructose-induced hyperglycemia, but
      caused dramatic hyperfructosemia (>1 mM) with reversed portal to systemic
      gradients. Systemic fructose in wild-type and KHK(-/-) mice changed by 0.34 and
      1.8 mM, respectively, for every millimolar increase in portal fructose
      concentration. Systemic glucose varied strongly with systemic, but not portal,
      fructose levels in wild-type, and was independent of systemic and portal fructose
      in KHK(-/-), mice. With ad libitum feeding for 12 wk, fructose-induced
      hyperglycemia in wild-type, but not hyperfructosemia in KHK(-/-) mice, increased
      HbA1c concentrations. Increasing dietary fructose to 40% intensified the
      hyperfructosemia of KHK(-/-) and the fructose-induced hyperglycemia of wild-type
      mice. Fructose perfusion or feeding in rats also caused duration- and dose
      dependent hyperfructosemia and hyperglycemia. Significant levels of blood
      fructose are maintained independent of dietary fructose, KHK, and GLUT5, probably
      by endogenous synthesis of fructose. KHK prevents hyperfructosemia and fructose
      induced hyperglycemia that would markedly increase HbA1c levels. These findings
      explain the hyperfructosemia of human hereditary fructosuria as well as the
      hyperglycemia of fructose-induced metabolic syndrome.

PMID- 26316590
TI  - "Store-operated" cAMP signaling contributes to Ca2+-activated Cl- secretion in
      T84 colonic cells.
AB  - Apical cAMP-dependent CFTR Cl(-) channels are essential for efficient vectorial
      movement of ions and fluid into the lumen of the colon. It is well known that
      Ca(2+)-mobilizing agonists also stimulate colonic anion secretion. However, CFTR
      is apparently not activated directly by Ca(2+), and the existence of apical
      Ca(2+)-dependent Cl(-) channels in the native colonic epithelium is
      controversial, leaving the identity of the Ca(2+)-activated component unresolved.
      We recently showed that decreasing free Ca(2+) concentration ([Ca(2+)]) within
      the endoplasmic reticulum (ER) lumen elicits a rise in intracellular cAMP. This
      process, which we termed "store-operated cAMP signaling" (SOcAMPS), requires the
      luminal ER Ca(2+) sensor STIM1 and does not depend on changes in cytosolic
      Ca(2+). Here we assessed the degree to which SOcAMPS participates in Ca(2+)
      activated Cl(-) transport as measured by transepithelial short-circuit current
      (Isc) in polarized T84 monolayers in parallel with imaging of cAMP and PKA
      activity using fluorescence resonance energy transfer (FRET)-based reporters in
      single cells. In Ca(2+)-free conditions, the Ca(2+)-releasing agonist carbachol
      and Ca(2+) ionophore increased Isc, cAMP, and PKA activity. These responses
      persisted in cells loaded with the Ca(2+) chelator BAPTA-AM. The effect on Isc
      was enhanced in the presence of the phosphodiesterase (PDE) inhibitor 3-isobutyl
      1-methylxanthine (IBMX), inhibited by the CFTR inhibitor CFTRinh-172 and the PKA
      inhibitor H-89, and unaffected by Ba(2+) or flufenamic acid. We propose that a
      discrete component of the "Ca(2+)-dependent" secretory activity in the colon
      derives from cAMP generated through SOcAMPS. This alternative mode of cAMP
      production could contribute to the actions of diverse xenobiotic agents that
      disrupt ER Ca(2+) homeostasis, leading to diarrhea. 

PMID- 26316591
TI  - Chronic alcohol exposure affects pancreatic acinar mitochondrial thiamin
      pyrophosphate uptake: studies with mouse 266-6 cell line and primary cells.
AB  - Thiamin is essential for normal metabolic activity of all mammalian cells,
      including those of the pancreas. Cells obtain thiamin from their surroundings and
      enzymatically convert it into thiamin pyrophosphate (TPP) in the cytoplasm; TPP
      is then taken up by mitochondria via a specific carrier the mitochondrial TPP
      transporter (MTPPT; product of the SLC25A19 gene). Chronic alcohol exposure
      negatively impacts the health of pancreatic acinar cells (PAC), but its effect on
      physiological/molecular parameters of MTPPT is not known. We addressed this issue
      using mouse pancreatic acinar tumor cell line 266-6 and primary PAC of wild-type
      and transgenic mice carrying the SLC25A19 promoter that were fed alcohol
      chronically. Chronic alcohol exposure of 266-6 cells (but not to its nonoxidative
      metabolites ethyl palmitate and ethyl oleate) led to a significant inhibition in
      mitochondrial TPP uptake, which was associated with a decreased expression of
      MTPPT protein, mRNA, and activity of the SLC25A19 promoter. Similarly, chronic
      alcohol feeding of mice led to a significant inhibition in expression of MTPPT
      protein, mRNA, heterogeneous nuclear RNA, as well as in activity of SLC25A19
      promoter in PAC. While chronic alcohol exposure did not affect DNA methylation of
      the Slc25a19 promoter, a significant decrease in histone H3 euchromatin markers
      and an increase in H3 heterochromatin marker were observed. These findings show,
      for the first time, that chronic alcohol exposure negatively impacts pancreatic
      MTPPT, and that this effect is exerted, at least in part, at the level of
      Slc25a19 transcription and appears to involve epigenetic mechanism(s).

PMID- 26316593
TI  - NEM1 acts as a suppressor of apoptotic phenotypes in LSM4 yeast mutants.
AB  - Saccharomyces cerevisiae mutants in the essential gene LSM4, involved in
      messenger RNA decapping, and expressing a truncated form of the LSM4 gene of the
      yeast Kluyveromyces lactis (Kllsm4Delta1), show premature aging accompanied by
      the presence of typical markers of apoptosis and high sensitivity to oxidative
      stressing agents. We isolated multicopy extragenic suppressors of these defects,
      transforming the Kllsm4Delta1 mutant with a yeast DNA library and selecting
      clones showing resistance to acetic acid. Here we present one of these clones,
      carrying a DNA fragment containing the NEM1 gene (Nuclear Envelope Morphology
      protein 1), which encodes the catalytic subunit of the Nem1p-Spo7p phosphatase
      holoenzyme. Nem1p regulates nuclear growth by controlling phospholipid
      biosynthesis and it is required for normal nuclear envelope morphology and
      sporulation. The data presented here correlate the mRNA metabolism with the
      biosynthesis of phospholipids and with the functionality of the endoplasmic
      reticulum. 

PMID- 26316592
TI  - Variants in pancreatic carboxypeptidase genes CPA2 and CPB1 are not associated
      with chronic pancreatitis.
AB  - Genetic alterations in the carboxypeptidase A1 gene (CPA1) are associated with
      early onset chronic pancreatitis (CP). Besides CPA1, there are two other human
      pancreatic carboxypeptidases (CPA2 and CPB1). Here we examined whether CPA2 and
      CPB1 alterations are associated with CP in Japan and Germany. All exons and
      flanking introns of CPA2 and CPB1 were sequenced in 477 Japanese patients with CP
      (234 alcoholic, 243 nonalcoholic) and in 497 German patients with nonalcoholic CP
      by targeted next-generation sequencing and/or Sanger sequencing. Secretion and
      enzymatic activity of CPA2 and CPB1 variants were determined after transfection
      into HEK 293T cells. We identified six nonsynonymous CPA2 variants (p.V67I,
      p.G166R, p.D168E, p.D173H, p.R237W, and p.G388S), eight nonsynonymous CPB1
      alterations (p.S65G, p.N120S, p.D172E, p.R195H, p.D208N, p.F232L, p.A317V, and
      p.D364Y), and one splice-site variant (c.687+1G>T) in CPB1. Functional analysis
      revealed essentially complete loss of function in CPA2 variants p.R237W and
      p.G388S and CPB1 variants p.R110H and p.D364Y. None of the CPA2 or CPB1 variants,
      including those resulting in a marked loss of function, were overrepresented in
      patients with CP. In conclusion, CPA2 and CPB1 variants are not associated with
      CP. 

PMID- 26316596
TI  - Editorial: Jurij Piskur (1960-2014).

PMID- 26316595
TI  - Responses to Tobacco Smoking-Related Health Messages in Young People With Recent
      Onset Schizophrenia.
AB  - Virtually no research has examined the responses of youth with recent-onset
      psychosis (ROP) to smoking-related health warnings. We examined predictors of
      response and tested hypotheses that participants with ROP would (a) assess
      warnings as less effective than a healthy comparison (HC) group, and (b) assess
      video warnings as more effective than pictures. ROP participants (n = 69) had <2
      years of prior antipsychotic treatment; the HC group (n = 79) had no major mental
      illness. Participants viewed 10 pictorial warnings, 8 videos depicting similar
      messages, and were interviewed regarding tobacco use, health literacy, and
      smoking knowledge. We assessed response at baseline and at 4-week follow-up. ROP
      participants were more likely than HC to smoke tobacco (49.3% vs 10.1%) and had
      lower levels of health literacy and smoking-related knowledge. Cannabis was used
      by 46.4% of ROP participants. Effectiveness ratings were high for both picture
      and video warnings with no differences between media. ROP participants compared
      to HC and nonsmokers compared to smokers were more likely to perceive warnings as
      effective. Effectiveness was associated with negative affect and greater
      emotional arousal. We assessed 33 smokers at follow-up; 5 (15%) identified as
      nonsmokers, 15 (45%) made a quit attempt, and 16 (49%) reported that the warnings
      influenced their smoking. Results indicate that young people with psychotic
      disorders respond favorably to health warnings. Effective messages depict health
      consequences clearly, elicit negative emotions, and may impact smoking behavior.
      Future research is needed to understand the effects of mode of presentation and
      message comprehension on smoking behavior. 

PMID- 26316594
TI  - Meta-analysis of Positive and Negative Symptoms Reveals Schizophrenia Modifier
      Genes.
AB  - BACKGROUND: Evidence suggests that genetic factors may influence both
      schizophrenia (Scz) and its clinical presentation. In recent years, genome-wide
      association studies (GWAS) have demonstrated considerable success in identifying
      risk loci. Detection of "modifier loci" has the potential to further elucidate
      underlying disease processes. METHODS: We performed GWAS of empirically derived
      positive and negative symptom scales in Irish cases from multiply affected
      pedigrees and a larger, independent case-control sample, subsequently combining
      these into a large Irish meta-analysis. In addition to single-SNP associations,
      we considered gene-based and pathway analyses to better capture convergent
      genetic effects, and to facilitate biological interpretation of these findings.
      Replication and testing of aggregate genetic effects was conducted using an
      independent European-American sample. RESULTS: Though no single marker met the
      genome-wide significance threshold, genes and ontologies/pathways were
      significantly associated with negative and positive symptoms; notably, NKAIN2 and
      NRG1, respectively. We observed limited overlap in ontologies/pathways associated
      with different symptom profiles, with immune-related categories over-represented
      for negative symptoms, and addiction-related categories for positive symptoms.
      Replication analyses suggested that genes associated with clinical presentation
      are generalizable to non-Irish samples. CONCLUSIONS: These findings strongly
      support the hypothesis that modifier loci contribute to the etiology of distinct
      Scz symptom profiles. The finding that previously implicated "risk loci" actually
      influence particular symptom dimensions has the potential to better delineate the
      roles of these genes in Scz etiology. Furthermore, the over-representation of
      distinct gene ontologies/pathways across symptom profiles suggests that the
      clinical heterogeneity of Scz is due in part to complex and diverse genetic
      factors.

PMID- 26316597
TI  - Clustering and Residual Confounding in the Application of Marginal Structural
      Models: Dialysis Modality, Vascular Access, and Mortality.
AB  - In the application of marginal structural models to compare time-varying
      treatments, it is rare that the hierarchical structure of a data set is accounted
      for or that the impact of unmeasured confounding on estimates is assessed. These
      issues often arise when analyzing data sets drawn from clinical registries, where
      patients may be clustered within health-care providers, and the amount of data
      collected from each patient may be limited by design (e.g., to reduce costs or
      encourage provider participation). We compared the survival of patients
      undergoing treatment with various dialysis types, where some patients switched
      dialysis modality during the course of their treatment, by estimating a marginal
      structural model using data from the Australia and New Zealand Dialysis and
      Transplant Registry, 2003-2011. The number of variables recorded by the registry
      is limited, and patients are clustered within the dialysis centers responsible
      for their treatment, so we assessed the impact of accounting for unmeasured
      confounding or clustering on estimated treatment effects. Accounting for
      clustering had limited impact, and only unreasonable levels of unmeasured
      confounding would have changed conclusions about treatment comparisons. Our
      analysis serves as a case study in assessing the impact of unmeasured confounding
      and clustering in the application of marginal structural models. 

PMID- 26316599
TI  - The Choice of Analytical Strategies in Inverse-Probability-of-Treatment-Weighted
      Analysis: A Simulation Study.
AB  - We sought to explore the impact of intention to treat and complex treatment use
      assumptions made during weight construction on the validity and precision of
      estimates derived from inverse-probability-of-treatment-weighted analysis. We
      simulated data assuming a nonexperimental design that attempted to quantify the
      effect of statin on lowering low-density lipoprotein cholesterol. We created 324
      scenarios by varying parameter values (effect size, sample size, adherence level,
      probability of treatment initiation, associations between low-density lipoprotein
      cholesterol and treatment initiation and continuation). Four analytical
      approaches were used: 1) assuming intention to treat; 2) assuming complex
      mechanisms of treatment use; 3) assuming a simple mechanism of treatment use; and
      4) assuming invariant confounders. With a continuous outcome, estimates assuming
      intention to treat were biased toward the null when there were nonnull treatment
      effect and nonadherence after treatment initiation. For each 1% decrease in the
      proportion of patients staying on treatment after initiation, the bias in
      estimated average treatment effect increased by 1%. Inverse-probability-of
      treatment-weighted analyses that took into account the complex mechanisms of
      treatment use generated approximately unbiased estimates. Studies estimating the
      actual effect of a time-varying treatment need to consider the complex mechanisms
      of treatment use during weight construction. 

PMID- 26316601
TI  - O-H hydrogen bonding promotes H-atom transfer from alpha C-H bonds for C
      alkylation of alcohols.
AB  - The efficiency and selectivity of hydrogen atom transfer from organic molecules
      are often difficult to control in the presence of multiple potential hydrogen
      atom donors and acceptors. Here, we describe the mechanistic evaluation of a mode
      of catalytic activation that accomplishes the highly selective photoredox alpha
      alkylation/lactonization of alcohols with methyl acrylate via a hydrogen atom
      transfer mechanism. Our studies indicate a particular role of tetra-n
      butylammonium phosphate in enhancing the selectivity for alpha C-H bonds in
      alcohols in the presence of allylic, benzylic, alpha-C=O, and alpha-ether C-H
      bonds. 

PMID- 26316600
TI  - Architecture of the fungal nuclear pore inner ring complex.
AB  - The nuclear pore complex (NPC) constitutes the sole gateway for bidirectional
      nucleocytoplasmic transport. We present the reconstitution and interdisciplinary
      analyses of the ~425-kilodalton inner ring complex (IRC), which forms the central
      transport channel and diffusion barrier of the NPC, revealing its interaction
      network and equimolar stoichiometry. The Nsp1*Nup49*Nup57 channel nucleoporin
      heterotrimer (CNT) attaches to the IRC solely through the adaptor nucleoporin
      Nic96. The CNT*Nic96 structure reveals that Nic96 functions as an assembly sensor
      that recognizes the three-dimensional architecture of the CNT, thereby mediating
      the incorporation of a defined CNT state into the NPC. We propose that the IRC
      adopts a relatively rigid scaffold that recruits the CNT to primarily form the
      diffusion barrier of the NPC, rather than enabling channel dilation. 

PMID- 26316602
TI  - A H(a)rd Way to Adapt in Cardiac Hypertrophy.

PMID- 26316603
TI  - The Neuroimmune Axis in the Kidney: Role in Hypertension.

PMID- 26316598
TI  - The Impact of Different CD4 Cell-Count Monitoring and Switching Strategies on
      Mortality in HIV-Infected African Adults on Antiretroviral Therapy: An
      Application of Dynamic Marginal Structural Models.
AB  - In Africa, antiretroviral therapy (ART) is delivered with limited laboratory
      monitoring, often none. In 2003-2004, investigators in the Development of
      Antiretroviral Therapy in Africa (DART) Trial randomized persons initiating ART
      in Uganda and Zimbabwe to either laboratory and clinical monitoring (LCM) or
      clinically driven monitoring (CDM). CD4 cell counts were measured every 12 weeks
      in both groups but were only returned to treating clinicians for management in
      the LCM group. Follow-up continued through 2008. In observational analyses,
      dynamic marginal structural models on pooled randomized groups were used to
      estimate survival under different monitoring-frequency and clinical/immunological
      switching strategies. Assumptions included no direct effect of randomized group
      on mortality or confounders and no unmeasured confounders which influenced
      treatment switch and mortality or treatment switch and time-dependent covariates.
      After 48 weeks of first-line ART, 2,946 individuals contributed 11,351 person
      years of follow-up, 625 switches, and 179 deaths. The estimated survival
      probability after a further 240 weeks for post-48-week switch at the first CD4
      cell count less than 100 cells/mm(3) or non-Candida World Health Organization
      stage 4 event (with CD4 count <250) was 0.96 (95% confidence interval (CI): 0.94,
      0.97) with 12-weekly CD4 testing, 0.96 (95% CI: 0.95, 0.97) with 24-weekly CD4
      testing, 0.95 (95% CI: 0.93, 0.96) with a single CD4 test at 48 weeks (baseline),
      and 0.92 (95% CI: 0.91, 0.94) with no CD4 testing. Comparing randomized groups by
      48-week CD4 count, the mortality risk associated with CDM versus LCM was greater
      in persons with CD4 counts of <100 (hazard ratio = 2.4, 95% CI: 1.3, 4.3) than in
      those with CD4 counts of >=100 (hazard ratio = 1.1, 95% CI: 0.8, 1.7; interaction
      P = 0.04). These findings support a benefit from identifying patients
      immunologically failing first-line ART at 48 weeks. 

PMID- 26316604
TI  - Bone Marrow Cell Therapy for Ischemic Heart Disease: The Never Ending Story.

PMID- 26316605
TI  - Allogeneic Precursor Cells for Systolic Heart Failure: A Need for Mechanisms in
      Humans.

PMID- 26316606
TI  - 2015 Lucian Award: Jeffery Molkentin.

PMID- 26316607
TI  - Letter by Mosley Regarding Article, "Iron Homeostasis and Pulmonary Hypertension:
      Iron Deficiency Leads to Pulmonary Vascular Remodeling in the Rat".

PMID- 26316609
TI  - Relationship Between Glenoid Defects and Hill-Sachs Lesions in Shoulders With
      Traumatic Anterior Instability.
AB  - BACKGROUND: While the combination of a glenoid defect and a Hill-Sachs lesion in
      a shoulder with anterior instability has recently been termed a bipolar lesion,
      their relationship is unclear. PURPOSE: To investigate the relationship of the
      glenoid defect and Hill-Sachs lesion and the factors that influence the
      occurrence of these lesions as well as the recurrence of instability. STUDY
      DESIGN: Case-control study; Level of evidence, 3. METHODS: The prevalence and
      size of both lesions were evaluated retrospectively by computed tomography
      scanning in 153 shoulders before arthroscopic Bankart repair. First, the
      relationship of lesion prevalence and size was investigated. Then, factors
      influencing the occurrence of bipolar lesions were assessed. Finally, the
      influence of these lesions on recurrence of instability was investigated in 103
      shoulders followed for a minimum of 2 years. RESULTS: Bipolar lesions, isolated
      glenoid defects/isolated Hill-Sachs lesions, and no lesion were detected in 86,
      45, and 22 shoulders (56.2%, 29.4%, and 14.4%), respectively. As the glenoid
      defect became larger, the Hill-Sachs lesion also increased in size. However, the
      size of these lesions showed a weak correlation, and large Hill-Sachs lesions did
      not always coexist with large glenoid defects. The prevalence of bipolar lesions
      was 33.3% in shoulders with primary instability and 61.8% in shoulders with
      recurrent instability. In relation to the total events of
      dislocations/subluxations, the prevalence was 44.2% in shoulders with 1 to 5
      events, 69.0% in shoulders with 6 to 10 events, and 82.8% in shoulders with >=11
      events. Regarding the type of sport, the prevalence was 58.9% in athletes playing
      collision sports, 53.3% in athletes playing contact sports, and 29.4% in athletes
      playing overhead sports. Postoperative recurrence of instability was 0% in
      shoulders without lesions, 0% with isolated Hill-Sachs lesions, 8.3% with
      isolated glenoid defects, and 29.4% with bipolar lesions. The presence of a
      bipolar lesion significantly influenced the recurrence rate, but lesion size did
      not. CONCLUSION: The prevalence of bipolar lesions was approximately 60%. As
      glenoid defects became larger, Hill-Sachs lesions also enlarged, but there was no
      strong correlation. Bipolar lesions were frequent in patients with recurrent
      instability, patients with repetitive dislocation/subluxation, and those playing
      collision/contact sports. Instability showed a high recurrence rate in shoulders
      with bipolar lesions.

PMID- 26316608
TI  - The Activation Function-1 of Estrogen Receptor Alpha Prevents Arterial Neointima
      Development Through a Direct Effect on Smooth Muscle Cells.
AB  - RATIONALE: 17beta-Estradiol (E2) exerts numerous beneficial effects in vascular
      disease. It regulates gene transcription through nuclear estrogen receptor alpha
      (ERalpha) via 2 activation functions, AF1 and AF2, and can also activate membrane
      ERalpha. The role of E2 on the endothelium relies on membrane ERalpha activation,
      but the molecular mechanisms of its action on vascular smooth muscle cells
      (VSMCs) are not fully understood. OBJECTIVE: The aim of this study was to
      determine which cellular target and which ERalpha subfunction are involved in the
      preventive action of E2 on neointimal hyperplasia. METHODS AND RESULTS: To
      trigger neointimal hyperplasia of VSMC, we used a mouse model of femoral arterial
      injury. Cre-Lox models were used to distinguish between the endothelial- and the
      VSMC-specific actions of E2. The molecular mechanisms underlying the role of E2
      were further characterized using both selective ERalpha agonists and transgenic
      mice in which the ERalphaAF1 function had been specifically invalidated. We found
      that (1) the selective inactivation of ERalpha in VSMC abrogates the neointimal
      hyperplasia protection induced by E2, whereas inactivation of endothelial and
      hematopoietic ERalpha has no effect; (2) the selective activation of membrane
      ERalpha does not prevent neointimal hyperplasia; and (3) ERalphaAF1 is necessary
      and sufficient to inhibit postinjury VSMC proliferation. CONCLUSIONS: Altogether,
      ERalphaAF1-mediated nuclear action is both necessary and sufficient to inhibit
      postinjury arterial VSMC proliferation, whereas membrane ERalpha largely
      regulates the endothelial functions of E2. This highlights the exquisite
      cell/tissue-specific actions of the ERalpha subfunctions and helps to delineate
      the spectrum of action of selective ER modulators.

PMID- 26316610
TI  - Patient Activity Levels After Reverse Total Shoulder Arthroplasty: What Are
      Patients Doing?
AB  - BACKGROUND: The indications for reverse total shoulder arthroplasty (RTSA)
      continue to expand, which has resulted in younger patients who want to remain
      active after RTSA. Little information is available to manage expectations of both
      physicians and patients for return to sporting activities. PURPOSE: To determine
      the rate of return to sporting activities and assess average time to return to
      sports after RTSA. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: This
      was a retrospective review of consecutive RTSA patients collected from our
      institution's shoulder arthroplasty registry. All patients who played sports
      preoperatively and had a minimum of 1-year follow-up were included. Final follow
      up consisted of an additional patient-reported questionnaire with questions
      regarding physical fitness and sporting activities. Each patient also completed
      an assessment with the American Shoulder and Elbow Society (ASES) Shoulder Score
      and a visual analog scale (VAS) for pain. RESULTS: Seventy-six patients played a
      sport preoperatively and met inclusion and exclusion criteria. The average follow
      up was 31.6 months (range, 12-65 months), and average age was 74.8 years (range,
      49.9-92.6 years). Average VAS pain scores improved from 6.57 to 0.63 (P < .001).
      Average ASES scores improved from 34.30 to 81.45 (P < .001). Subjectively, 11.8%
      of patients complained of stiffness and 10.5% complained of chronic pain. After
      RTSA, 85.5% of patients returned to at least 1 sport. Average time to return to
      full sports was 5.3 months. Fitness sports had the highest direct rate of return
      (81.5%), followed by swimming (66.7%), running (57.1%), cycling (50.0%), and golf
      (50%). Postoperatively, 41.1% of patients reported improved physical fitness;
      88.2% felt that their sports outcome was good to excellent, and 93.4% felt that
      their surgical outcome was good to excellent. CONCLUSION: Patients undergoing
      RTSA had an 85% rate of return to 1 or more sporting activities at an average of
      5.3 months after surgery. Age greater than 70 years was a significant predictor
      of decreased return to activities. The present study offers valuable information
      to help manage patient and surgeon expectations.

PMID- 26316611
TI  - Return to Sport After Rotator Cuff Tear Repair: A Systematic Review and Meta
      analysis.
AB  - BACKGROUND: One of the most frequent demands from athletes after rotator cuff
      tear repair is to return to sport, if possible at the same level of play.
      PURPOSE: The main goal of this study was to determine the rate of return to sport
      after treatment of rotator cuff tears. STUDY DESIGN: Meta-analysis and systematic
      review. METHODS: The PRISMA (Preferred Reporting Items for Systematic Reviews and
      Meta-Analyses) guidelines were followed to perform this systematic review and
      meta-analysis of the results in the literature, as well as for the presentation
      of results. A search of the literature was performed on the electronic databases
      MEDLINE, Scopus, EMBASE, and the Cochrane Library. The quality of the included
      studies was evaluated according to the MINORS (Methodological Index for
      Nonrandomized Studies) checklist. Inclusion criteria were studies in English
      evaluating return to sport after treatment of traumatic, degenerative, partial or
      full-thickness rotator cuff tears in patients practicing a sport regularly,
      whatever the level, all ages and sports included. The main judgment criterion was
      the number of patients who returned to a sports activity after treatment of a
      rotator cuff tear. The criterion was analyzed in 2 ways: return to sport (yes/no)
      and the level of play (identical or higher/lower level). RESULTS: Twenty-five
      studies were reviewed, including 859 patients (683 athletes), all treated
      surgically after a mean follow-up of 3.4 years (range, 0.3-13.4 years). The level
      of sports was recorded in 23 studies or 635 (93%) athletes and included 286
      competitive or professional athletes and 349 recreational athletes. The most
      commonly practiced sports were baseball (224 participants), tennis (104
      participants), and golf (54 participants). The overall rate of return to sport
      was 84.7% (95% CI, 77.6%-89.8%), including 65.9% (95% CI, 54.9%-75.4%) at an
      equivalent level of play, after 4 to 17 months. Of the professional and
      competitive athletes, 49.9% (95% CI, 35.3-64.6%) returned to the same level of
      play. CONCLUSION: Most recreational athletes return to sports at the same level
      of play as before their injury, but only half of professional and competitive
      athletes return to an equivalent level of play.

PMID- 26316612
TI  - Secretion of Wnts is dispensable for hematopoiesis.
AB  - In this issue of Blood, Kabiri and coworkers report the hematopoietic deletion of
      the endoplasmic reticulum-localized O-acyltransferase porcupine (PORCN), which is
      necessary for acylation of Wnts in the endoplasmic reticulum, enabling their
      secretion and binding to the frizzled receptors. Unexpectedly, the absence of
      secreted Wnt factors does not have major effects on steady-state in vivo
      hematopoiesis or on long-term repopulating activity of Wnt-deficient
      hematopoietic stem cells.

PMID- 26316613
TI  - A vaccine against HTLV-1 HBZ makes sense.
AB  - In this issue of Blood, Sugata et al report that vaccination against human T-cell
      leukemia virus type 1 (HTLV-1) basic leucine zipper (bZIP) factor (HBZ) could be
      used for immunotherapy in adult T-cell leukemia-lymphoma (ATL) patients.

PMID- 26316614
TI  - Exosomes and CAFs: partners in crime.
AB  - In this issue of Blood, Paggetti et al present novel findings that chronic
      lymphocytic leukemia (CLL)-derived exosomes and their molecular cargo are
      actively transferred to stromal cells that reside in the lymphoid tumor
      microenvironment (TME), promoting the reprogramming of these cells into cancer
      associated fibroblasts (CAFs).

PMID- 26316615
TI  - Membrane grease eases platelet maturation.
AB  - In this issue of Blood, Valet et al1 report a novel regulatory role of class II
      phosphoinositide 3-kinase (PI3K)-C2alpha in the morphology and remodeling of
      platelet membranes and its implications in platelet maturation and arterial
      thrombosis.

PMID- 26316617
TI  - Rethinking the Focus of Heart Failure Quality Measures.

PMID- 26316616
TI  - Medication Initiation Burden Required to Comply With Heart Failure Guideline
      Recommendations and Hospital Quality Measures.
AB  - BACKGROUND: Guidelines for heart failure (HF) recommend prescription of guideline
      directed medical therapy before hospital discharge; some of these therapies are
      included in publicly reported performance measures. The burden of new medications
      for individual patients has not been described. METHODS AND RESULTS: We used Get
      With The Guidelines-HF registry data from 2008 to 2013 to characterize
      prescribing, indications, and contraindications for angiotensin-converting enzyme
      inhibitors or angiotensin receptor blockers, beta-blockers, aldosterone
      antagonists, hydralazine/isosorbide dinitrate, and anticoagulants. The difference
      between a patient's medication regimen at hospital admission and that recommended
      by HF quality measures at discharge was calculated. Among 158 922 patients from
      271 hospitals with a primary discharge diagnosis of HF, initiation of angiotensin
      converting enzyme inhibitors or angiotensin receptor blockers was indicated in
      18.1% of all patients (55.5% of those eligible at discharge were not receiving
      angiotensin-converting enzyme inhibitors or angiotensin receptor blockers at
      admission), beta-blockers in 20.3% (50.5% of eligible), aldosterone antagonists
      in 24.1% (87.4% of eligible), hydralazine/isosorbide dinitrate in 8.6% (93.1% of
      eligible), and anticoagulants in 18.0% (58.0% of eligible). Cumulatively, 0.4% of
      patients were eligible for 5 new medication groups, 4.1% for 4 new medication
      groups, 9.4% for 3 new medication groups, 10.1% for 2 new medication groups, and
      22.7% for 1 new medication group; 15.0% were not eligible for new medications
      because of adequate prescribing at admission; and 38.4% were not eligible for any
      medications recommended by HF quality measures. Compared with newly indicated
      medications (mean, 1.45 +/- 1.23), actual new prescriptions were lower (mean,
      1.16 +/- 1.00). CONCLUSIONS: A quarter of patients hospitalized with HF need to
      start >1 medication to meet HF quality measures. Systems for addressing
      medication initiation and managing polypharmacy are central to HF transitional
      care.

PMID- 26316618
TI  - Use of the wearable cardioverter defibrillator in high-risk cardiac patients:
      data from the Prospective Registry of Patients Using the Wearable Cardioverter
      Defibrillator (WEARIT-II Registry).
AB  - BACKGROUND: Prospective data on the safety and efficacy of the wearable
      cardioverter defibrillator (WCD) in a real-world setting are lacking. The
      Prospective Registry of Patients Using the Wearable Defibrillator (WEARIT-II)
      Registry was designed to provide real-world data on the WCD as a strategy during
      a period of risk stratification. METHODS AND RESULTS: The WEARIT-II Registry
      enrolled 2000 patients with ischemic (n=805, 40%), or nonischemic cardiomyopathy
      (n=927, 46%), or congenital/inherited heart disease (n=268) prescribed WCD
      between August 2011 and February 2014. Clinical data, arrhythmia events,
      implantable cardioverter defibrillator implantation, and improvement in ejection
      fraction were captured. The median age was 62 years; the median ejection fraction
      was 25%. The median WCD wear time was 90 days, with median daily use of 22.5
      hours. There was a total of 120 sustained ventricular tachyarrhythmias in 41
      patients, of whom 54% received appropriate WCD shock. Only 10 patients (0.5%)
      received inappropriate WCD therapy. The rate of sustained ventricular
      tachyarrhythmias by 3 months was 3% among patients with ischemic cardiomyopathy
      and congenital/inherited heart disease, and 1% among nonischemic patients
      (P=0.02). At the end of WCD use, 840 patients (42%) were implanted with an
      implantable cardioverter defibrillator. The most frequent reason not to implant
      an implantable cardioverter defibrillator following WCD use was improvement in
      ejection fraction. CONCLUSIONS: The WEARIT-II Registry demonstrates a high rate
      of sustained ventricular tachyarrhythmias at 3 months in at-risk patients who are
      not eligible for an implantable cardioverter defibrillator, and suggests that the
      WCD can be safely used to protect patients during this period of risk assessment.

PMID- 26316619
TI  - Risk of Obstructive Sleep Apnea: Sex Matters.

PMID- 26316620
TI  - Sex-Specific Association of Sleep Apnea Severity With Subclinical Myocardial
      Injury, Ventricular Hypertrophy, and Heart Failure Risk in a Community-Dwelling
      Cohort: The Atherosclerosis Risk in Communities-Sleep Heart Health Study.
AB  - BACKGROUND: Risk factors for obstructive sleep apnea (OSA) and the development of
      subsequent cardiovascular (CV) complications differ by sex. We hypothesize that
      the relationship between OSA and high-sensitivity troponin T (hs-TnT), cardiac
      structure, and CV outcomes differs by sex. METHODS AND RESULTS: Seven hundred
      fifty-two men and 893 women free of CV disease participating in both the
      Atherosclerosis Risk in the Communities and the Sleep Heart Health Studies were
      included. All participants (mean age, 62.5 +/- 5.5 years) underwent
      polysomnography and measurement of hs-TnT. OSA severity was defined by using
      established clinical categories. Subjects were followed for 13.6 +/- 3.2 years
      for incident coronary disease, heart failure, and CV and all-cause mortality.
      Surviving subjects underwent echocardiography after 15.2 +/- 0.8 years. OSA was
      independently associated with hs-TnT among women (P=0.03) but not in men
      (P=0.94). Similarly, OSA was associated with incident heart failure or death in
      women (P=0.01) but not men (P=0.10). This association was no longer significant
      after adjusting for hs-TnT (P=0.09). Among surviving participants without an
      incident CV event, OSA assessed in midlife was independently associated with
      higher left ventricle mass index only among women (P=0.001). CONCLUSIONS: Sex
      specific differences exist in the relationship between OSA and CV disease. OSA,
      assessed in midlife, is independently associated with higher levels of
      concomitantly measured hs-TnT among women but not men, in whom other
      comorbidities associated with OSA may play a more important role. During 13-year
      follow-up, OSA was associated with incident heart failure or death only among
      women, and, among those without an incident event, it was independently
      associated with left ventricular hypertrophy only in women.

PMID- 26316621
TI  - Eculizumab in Pediatric Dense Deposit Disease.
AB  - BACKGROUND AND OBJECTIVES: Dense deposit disease (DDD), a subtype of C3
      glomerulopathy, is a rare disease affecting mostly children. Treatment options
      are limited. Debate exists whether eculizumab, a monoclonal antibody against
      complement factor C5, is effective in DDD. Reported data are scarce, especially
      in children. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The authors analyzed
      clinical and histologic data of five pediatric patients with a native kidney
      biopsy diagnosis of DDD. Patients received eculizumab as therapy of last resort
      for severe nephritic or nephrotic syndrome with alternative pathway complement
      activation; this therapy was given only when the patients had not or only
      marginally responded to immunosuppressive therapy. Outcome measures were kidney
      function, proteinuria, and urine analysis. RESULTS: In all, seven disease
      episodes were treated with eculizumab (six episodes of severe nephritic syndrome
      [two of which required dialysis] and one nephrotic syndrome episode). Median age
      at treatment start was 8.4 (range, 5.9-13) years. For three treatment episodes,
      eculizumab was the sole immunosuppressive treatment. In all patients, both
      proteinuria and renal function improved significantly within 12 weeks of
      treatment (median urinary protein-to-creatinine ratio of 8.5 [range, 2.2-17]
      versus 1.1 [range, 0.2-2.0] g/g, P<0.005, and eGFR of 58 [range, 17-114] versus
      77 [range, 50-129] ml/min per 1.73 m(2), P<0.01). A striking finding was the
      disappearance of leukocyturia within 1 week after the first eculizumab dose in
      all five episodes with leukocyturia at treatment initiation. CONCLUSIONS: In this
      case series of pediatric patients with DDD, eculizumab treatment was associated
      with reduction in proteinuria and increase in eGFR. Leukocyturia resolved within
      1 week of initiation of eculizumab treatment. These results underscore the need
      for a randomized trial of eculizumab in DDD.

PMID- 26316622
TI  - Quality Measures for Dialysis: Time for a Balanced Scorecard.
AB  - Recent federal legislation establishes a merit-based incentive payment system for
      physicians, with a scorecard for each professional. The Centers for Medicare and
      Medicaid Services evaluate quality of care with clinical performance measures and
      have used these metrics for public reporting and payment to dialysis facilities.
      Similar metrics may be used for the future merit-based incentive payment system.
      In nephrology, most clinical performance measures measure processes and
      intermediate outcomes of care. These metrics were developed from population
      studies of best practice and do not identify opportunities for individualizing
      care on the basis of patient characteristics and individual goals of treatment.
      The In-Center Hemodialysis (ICH) Consumer Assessment of Healthcare Providers and
      Systems (CAHPS) survey examines patients' perception of care and has entered the
      arena to evaluate quality of care. A balanced scorecard of quality performance
      should include three elements: population-based best clinical practice, patient
      perceptions, and individually crafted patient goals of care. 

PMID- 26316623
TI  - Paris-Trousseau thrombocytopenia is phenocopied by the autosomal recessive
      inheritance of a DNA-binding domain mutation in FLI1.
AB  - Hemizygous deletion of a variable region on chromosome 11q containing FLI1 causes
      an inherited platelet-related bleeding disorder in Paris-Trousseau
      thrombocytopenia and Jacobsen syndrome. These multisystem disorders are also
      characterized by heart anomalies, changes in facial structure, and intellectual
      disability. We have identified a consanguineous family with autosomal recessive
      inheritance of a bleeding disorder that mimics Paris-Trousseau thrombocytopenia
      but has no other features of the 11q23 deletion syndrome. Affected individuals in
      this family have moderate thrombocytopenia; absent collagen-induced platelet
      aggregation; and large, fused alpha-granules in 1% to 5% of circulating
      platelets. This phenotype was caused by a FLI1 homozygous c.970C>T-point mutation
      that predicts an arginine-to-tryptophan substitution in the conserved ETS DNA
      binding domain of FLI1. This mutation caused a transcription defect at the
      promoter of known FLI1 target genes GP6, GP9, and ITGA2B, as measured by
      luciferase assay in HEK293 cells, and decreased the expression of these target
      proteins in affected members of the family as measured by Western blotting of
      platelet lysates. This kindred suggests abnormalities in FLI1 as causative of
      Paris-Trousseau thrombocytopenia and confirms the important role of FLI1 in
      normal platelet development. 

PMID- 26316626
TI  - Gaps in paediatric rotas mean that GPs must do more in community, says royal
      college.

PMID- 26316624
TI  - Presence of multiple recurrent mutations confers poor trial outcome of
      relapsed/refractory CLL.
AB  - Although TP53, NOTCH1, and SF3B1 mutations may impair prognosis of patients with
      chronic lymphocytic leukemia (CLL) receiving frontline therapy, the impact of
      these mutations or any other, alone or in combination, remains unclear at
      relapse. The genome of 114 relapsed/refractory patients included in prospective
      trials was screened using targeted next-generation sequencing of the TP53, SF3B1,
      ATM, NOTCH1, XPO1, SAMHD1, MED12, BIRC3, and MYD88 genes. We performed clustering
      according to both number and combinations of recurrent gene mutations. The number
      of genes affected by mutation was >= 2, 1, and 0 in 43 (38%), 49 (43%), and 22
      (19%) respectively. Recurrent combinations of >= 2 mutations of TP53, SF3B1, and
      ATM were found in 22 (19%) patients. This multiple-hit profile was associated
      with a median progression-free survival of 12 months compared with 22.5 months in
      the remaining patients (P = .003). Concurrent gene mutations are frequent in
      patients with relapsed/refractory CLL and are associated with worse outcome.

PMID- 26316627
TI  - Deaths from cardiovascular disease are four times higher in eastern Europe than
      western Europe.

PMID- 26316625
TI  - Impaired platelet activation and cAMP homeostasis in MRP4-deficient mice.
AB  - Molecules that reduce the level of cyclic adenosine 5'-monophosphate (cAMP) in
      the platelet cytosol, such as adenosine 5'-diphosphate (ADP) secreted from dense
      granules, trigger platelet activation. Therefore, any change in the distribution
      and/or availability of cyclic nucleotides or ADP may interfere with platelet
      reactivity. In this study, we evaluated the role of multidrug resistance protein
      4 (MRP4, or ABCC4), a nucleotide transporter, in platelet functions in vivo and
      in vitro by investigating MRP4-deficient mice. MRP4 deletion resulted in a slight
      increase in platelet count but had no impact on platelet ultrastructure. In MRP4
      deficient mice, the arterial occlusion was delayed and the tail bleeding time was
      prolonged. In a model of platelet depletion and transfusion mimicking a platelet
      specific knockout, mice injected with MRP4(-/-) platelets also showed a
      significant increase in blood loss compared with mice injected with wild-type
      platelets. Defective thrombus formation and platelet activation were confirmed in
      vitro by studying platelet adhesion to collagen in flow conditions, integrin
      alphaIIbbeta3 activation, washed platelet secretion, and aggregation induced by
      low concentrations of proteinase-activated receptor 4-activating peptide, U46619,
      or ADP. We found no role of MRP4 in ADP dense-granule storage, but MRP4
      redistributed cAMP from the cytosol to dense granules, as confirmed by increased
      vasodilator-stimulated phosphoprotein phosphorylation in MRP4-deficient
      platelets. These data suggest that MRP4 promotes platelet aggregation by
      modulating the cAMP-protein kinase A signaling pathway, suggesting that MRP4
      might serve as a target for novel antiplatelet agents. 

PMID- 26316628
TI  - NHS received almost 4000 written complaints every week last year.

PMID- 26316629
TI  - Association Between Plantar Temperatures and Triaxial Stresses in Individuals
      With Diabetes.

PMID- 26316630
TI  - Feasibility of Outpatient 24-Hour Closed-Loop Insulin Delivery.

PMID- 26316631
TI  - Genome Sequence of Microbacterium sp. Strain 3J1, a Highly Desiccation-Tolerant
      Bacterium That Promotes Plant Growth.
AB  - The genome sequence for Microbacterium sp. strain 3J1, a desiccation-tolerant
      organism isolated from the Nerium oleander rhizosphere, is reported here. The
      genome is estimated to be approximately 3.5 Mb in size, with an average G+C
      content of 67.7% and a predicted number of protein-coding sequences of 3,310. 

PMID- 26316632
TI  - Draft Genome Sequence of Mycobacterium heckeshornense Strain RLE.
AB  - We report here the draft genome sequence of Mycobacterium heckeshornense strain
      RLE isolated from a sputum sample from a patient with shortness of breath. This
      is the first draft genome sequence of M. heckeshornense. 

PMID- 26316633
TI  - Draft Genome Sequence of Dysgonomonas macrotermitis Strain JCM 19375T, Isolated
      from the Gut of a Termite.
AB  - Here, we report the draft genome sequence of Dysgonomonas macrotermitis strain
      JCM 19375(T), which was isolated from the hindgut of a fungus-growing termite,
      Macrotermes barneyi. The genome information reveals the role of this strain in
      lignocellulose degradation and adaptation to the gut environment. 

PMID- 26316634
TI  - Complete Genome Sequences of Two Bordetella hinzii Strains Isolated from Humans.
AB  - Bordetella hinzii is primarily recovered from poultry but can also colonize
      mammalian hosts and immunocompromised humans. Here, we report the first complete
      genome sequences of B. hinzii in two isolates recovered from humans. The
      availability of these sequences will hopefully aid in identifying host-specific
      determinants variably present within this species. 

PMID- 26316635
TI  - Draft Genome Sequence of Alteromonas macleodii Strain MIT1002, Isolated from an
      Enrichment Culture of the Marine Cyanobacterium Prochlorococcus.
AB  - Alteromonas spp. are heterotrophic gammaproteobacteria commonly found in marine
      environments. We present here the draft genome sequence of Alteromonas macleodii
      MIT1002, which was isolated from an enrichment culture of the marine
      cyanobacterium Prochlorococcus NATL2A. This genome contains a mixture of features
      previously seen only within either the "surface" or "deep" Alteromonas ecotype. 

PMID- 26316636
TI  - Complete Genome Sequence of Paenibacillus larvae MEX14, Isolated from Honey Bee
      Larvae from the Xochimilco Quarter in Mexico City.
AB  - Paenibacillus larvae strain MEX14 is a facultative anaerobic endospore-forming
      bacterium that infects Apis mellifera larvae. Strain MEX14 was isolated from
      domestic bee larvae collected in a backyard in Mexico City. The estimated genome
      size was determined to be 4.18 Mb, and it harbors 4,806 protein coding genes
      (CDSs). 

PMID- 26316637
TI  - Genome Sequence of Aeribacillus pallidus Strain GS3372, an Endospore-Forming
      Bacterium Isolated in a Deep Geothermal Reservoir.
AB  - The genome of strain GS3372 is the first publicly available strain of
      Aeribacillus pallidus. This endospore-forming thermophilic strain was isolated
      from a deep geothermal reservoir. The availability of this genome can contribute
      to the clarification of the taxonomy of the closely related Anoxybacillus,
      Geobacillus, and Aeribacillus genera. 

PMID- 26316638
TI  - Genome Sequence of Bacillus alveayuensis Strain 24KAM51, a Halotolerant
      Thermophile Isolated from a Hydrothermal Vent.
AB  - Bacillus alveayuensis strain 24KAM51 was isolated from a marine hydrothermal vent
      in Milos, Greece. Its genome depicts interesting features of halotolerance and
      resistance to heavy metals. 

PMID- 26316639
TI  - Draft Genome Sequences of Two IMP-4-Producing Escherichia coli Sequence Type 131
      Isolates in Australia.
AB  - We report the draft genome sequences of two unrelated cases of Escherichia coli
      sequence type 131 (ST131) possessing the carbapenemase gene blaIMP-4. The E. coli
      ST131 SN5 isolate also possessed blaSHV-12 and plasmid-mediated quinolone
      resistance genes. Wider dissemination of blaIMP-4 may occur due to the blaIMP-4
      carrying L/M or HI2 plasmids among E. coli ST131 isolates. 

PMID- 26316640
TI  - Draft Genome Sequence of Aquamicrobium defluvii Strain W13Z1, a Psychrotolerant
      Halotolerant Hydrocarbon-Degrading Bacterium.
AB  - Aquamicrobium defluvii W13Z1 was isolated from petroleum-contaminated drill
      cuttings from the Bohai Sea and could degrade petroleum hydrocarbon with 5% NaCl
      at 15 degrees C. Here, we present the 4.8-Mb draft genome sequence of this
      strain, which may provide useful information about the mechanism of petroleum
      degradation in drill cuttings. 

PMID- 26316641
TI  - Correction for Vega-Alvarado et al., High-Quality Draft Genome Sequence of
      Candida apicola NRRL Y-50540.

PMID- 26316642
TI  - Risk prediction models for contrast induced nephropathy: systematic review.
AB  - OBJECTIVES: To look at the available literature on validated prediction models
      for contrast induced nephropathy and describe their characteristics. DESIGN:
      Systematic review. DATA SOURCES: Medline, Embase, and CINAHL (cumulative index to
      nursing and allied health literature) databases. REVIEW METHODS: Databases
      searched from inception to 2015, and the retrieved reference lists hand searched.
      Dual reviews were conducted to identify studies published in the English language
      of prediction models tested with patients that included derivation and validation
      cohorts. Data were extracted on baseline patient characteristics, procedural
      characteristics, modelling methods, metrics of model performance, risk of bias,
      and clinical usefulness. Eligible studies evaluated characteristics of predictive
      models that identified patients at risk of contrast induced nephropathy among
      adults undergoing a diagnostic or interventional procedure using conventional
      radiocontrast media (media used for computed tomography or angiography, and not
      gadolinium based contrast). RESULTS: 16 studies were identified, describing 12
      prediction models. Substantial interstudy heterogeneity was identified, as a
      result of different clinical settings, cointerventions, and the timing of
      creatinine measurement to define contrast induced nephropathy. Ten models were
      validated internally and six were validated externally. Discrimination varied in
      studies that were validated internally (C statistic 0.61-0.95) and externally
      (0.57-0.86). Only one study presented reclassification indices. The majority of
      higher performing models included measures of pre-existing chronic kidney
      disease, age, diabetes, heart failure or impaired ejection fraction, and
      hypotension or shock. No prediction model evaluated its effect on clinical
      decision making or patient outcomes. CONCLUSIONS: Most predictive models for
      contrast induced nephropathy in clinical use have modest ability, and are only
      relevant to patients receiving contrast for coronary angiography. Further
      research is needed to develop models that can better inform patient centred
      decision making, as well as improve the use of prevention strategies for contrast
      induced nephropathy.

PMID- 26316644
TI  - Are prolific authors too much of a good thing?

PMID- 26316643
TI  - Chemoenzymatic Synthesis, Characterization, and Scale-Up of Milk Thistle
      Flavonolignan Glucuronides.
AB  - Plant-based therapeutics, including herbal products, continue to represent a
      growing facet of the contemporary health care market. Mechanistic descriptions of
      the pharmacokinetics and pharmacodynamics of constituents composing these
      products remain nascent, particularly for metabolites produced following herbal
      product ingestion. Generation and characterization of authentic metabolite
      standards are essential to improve the quantitative mechanistic understanding of
      herbal product disposition in both in vitro and in vivo systems. Using the model
      herbal product, milk thistle, the objective of this work was to biosynthesize
      multimilligram quantities of glucuronides of select constituents (flavonolignans)
      to fill multiple knowledge gaps in the understanding of herbal product
      disposition and action. A partnership between clinical pharmacology and natural
      products chemistry expertise was leveraged to optimize reaction conditions for
      efficient glucuronide formation and evaluate alternate enzyme and reagent sources
      to improve cost effectiveness. Optimized reaction conditions used at least one
      fourth the amount of microsomal protein (from bovine liver) and cofactor (UDP
      glucuronic acid) compared with typical conditions using human-derived subcellular
      fractions, providing substantial cost savings. Glucuronidation was flavonolignan
      dependent. Silybin A, silybin B, isosilybin A, and isosilybin B generated five,
      four, four, and three monoglucuronides, respectively. Large-scale synthesis (40
      mg of starting material) generated three glucuronides of silybin A: silybin A-7-O
      beta-D-glucuronide (15.7 mg), silybin A-5-O-beta-D-glucuronide (1.6 mg), and
      silybin A-4''-O-beta-D-glucuronide (11.1 mg). This optimized, cost-efficient
      method lays the foundation for a systematic approach to synthesize and
      characterize herbal product constituent glucuronides, enabling an improved
      understanding of mechanisms underlying herbal product disposition and action.

PMID- 26316645
TI  - The RTS,S/AS01 vaccine continues to show modest protection against malaria in
      African infants and children.

PMID- 26316646
TI  - Association between probable postnatal depression and increased infant mortality
      and morbidity: findings from the DON population-based cohort study in rural
      Ghana.
AB  - OBJECTIVES: To assess the impact of probable depression in the immediate
      postnatal period on subsequent infant mortality and morbidity. DESIGN: Cohort
      study nested within 4 weekly surveillance of all women of reproductive age to
      identify pregnancies and collect data on births and deaths. SETTING:
      Rural/periurban communities within the Kintampo Health Research Centre study area
      of the Brong-Ahafo Region of Ghana. PARTICIPANTS: 16,560 mothers who had a live
      singleton birth reported between 24 March 2008 and 11 July 2009, who were
      screened for probable postnatal depression (pPND) between 4 and 12 weeks post
      partum (some of whom had also had depression assessed at pregnancy), and whose
      infants survived to this point. PRIMARY/SECONDARY OUTCOME MEASURES: All-cause
      early infant mortality expressed per 1000 infant-months of follow-up from the
      time of postnatal assessment to 6 months of age. The secondary outcomes were (1)
      all-cause infant mortality from the time of postnatal assessment to 12 months of
      age and (2) reported infant morbidity from the time of the postnatal assessment
      to 12 months of age. RESULTS: 130 infant deaths were recorded and singletons were
      followed for 67,457.4 infant-months from the time of their mothers' postnatal
      depression assessment. pPND was associated with an almost threefold increased
      risk of mortality up to 6 months (adjusted rate ratio (RR), 2.86 (1.58 to 5.19);
      p=0.001). The RR up to 12 months was 1.88 (1.09 to 3.24; p=0.023). pPND was also
      associated with increased risk of infant morbidity. CONCLUSIONS: There is new
      evidence for the association between maternal pPND and infant mortality in low
      income and middle-income countries. Implementation of the WHO's Mental Health Gap
      Action Programme (mhGAP) to scale up packages of care integrated with maternal
      health is encouraged as an important adjunct to child survival efforts.

PMID- 26316647
TI  - Patient and organisational variables associated with pressure ulcer prevalence in
      hospital settings: a multilevel analysis.
AB  - OBJECTIVES: To investigate the association of ward-level differences in the odds
      of hospital-acquired pressure ulcers (HAPUs) with selected ward organisational
      variables and patient risk factors. DESIGN: Multilevel approach to data from 2
      cross-sectional studies. SETTINGS: 4 hospitals in Norway were studied.
      PARTICIPANTS: 1056 patients at 84 somatic wards. PRIMARY OUTCOME MEASURE: HAPU.
      RESULTS: Significant variance in the odds of HAPUs was found across wards. A
      regression model using only organisational variables left a significant variance
      in the odds of HAPUs across wards but patient variables eliminated the across
      ward variance. In the model including organisational and patient variables,
      significant ward-level HAPU variables were ward type (rehabilitation vs
      surgery/internal medicine: OR 0.17 (95% CI 0.04 to 0.66)), use of preventive
      measures (yes vs no: OR 2.02 (95% CI 1.12 to 3.64)) and ward patient safety
      culture (OR 0.97 (95% CI 0.96 to 0.99)). Significant patient-level predictors
      were age >70 vs <70 (OR 2.70 (95% CI 1.54 to 4.74)), Braden scale total score (OR
      0.73 (95% CI 0.67 to 0.80)) and overweight (body mass index 25-29.99 kg/m(2)) (OR
      0.32 (95% CI 0.17 to 0.62)). CONCLUSIONS: The fact that the odds of HAPU varied
      across wards, and that across-ward variance was reduced when the selected ward
      level variables entered the explanatory model, indicates that the HAPU problem
      may be reduced by ward-level organisation of care improvements, that is, by
      improving the patient safety culture and implementation of preventive measures.
      Some wards may prevent pressure ulcers better than other wards. The fact that
      ward-level variation was eliminated when patient-level HAPU variables were
      included in the model indicates that even wards with the best HAPU prevention
      will be challenged by an influx of high-risk patients.

PMID- 26316648
TI  - Challenges faced by primary care physicians when prescribing for patients with
      chronic diseases in a teaching hospital in Malaysia: a qualitative study.
AB  - OBJECTIVE: The aim of this study was to identify the challenges faced by primary
      care physicians (PCPs) when prescribing medications for patients with chronic
      diseases in a teaching hospital in Malaysia. DESIGN/SETTING: 3 focus group
      discussions were conducted between July and August 2012 in a teaching primary
      care clinic in Malaysia. A topic guide was used to facilitate the discussions
      which were audio-recorded, transcribed verbatim and analysed using a thematic
      approach. PARTICIPANTS: PCPs affiliated to the primary care clinic were
      purposively sampled to include a range of clinical experience. Sample size was
      determined by thematic saturation of the data. RESULTS: 14 family medicine
      trainees and 5 service medical officers participated in this study. PCPs faced
      difficulties in prescribing for patients with chronic diseases due to a lack of
      communication among different healthcare providers. Medication changes made by
      hospital specialists, for example, were often not communicated to the PCPs
      leading to drug duplications and interactions. The use of paper-based medical
      records and electronic prescribing created a dual record system for patients'
      medications and became a problem when the 2 records did not tally. Patients
      sometimes visited different doctors and pharmacies for their medications and this
      resulted in the lack of continuity of care. PCPs also faced difficulties in
      addressing patients' concerns, and dealing with patients' medication requests and
      adherence issues. Some PCPs lacked time and knowledge to advise patients about
      their medications and faced difficulties in managing side effects caused by the
      patients' complex medication regimen. CONCLUSIONS: PCPs faced prescribing
      challenges related to patients, their own practice and the local health system
      when prescribing for patients with chronic diseases. These challenges must be
      addressed in order to improve chronic disease management in primary care and,
      more importantly, patient safety.

PMID- 26316649
TI  - Developing a best practice pathway to support improvements in Indigenous
      Australians' mental health and well-being: a qualitative study.
AB  - OBJECTIVE: There is a need to adapt pathways to care to promote access to mental
      health services for Indigenous people in Australia. This study explored
      Indigenous community and service provider perspectives of well-being and ways to
      promote access to care for Indigenous people at risk of depressive illness.
      DESIGN: A participatory action research framework was used to inform the
      development of an agreed early intervention pathway; thematic analysis SETTING: 2
      remote communities in the Northern Territory. PARTICIPANTS: Using snowball and
      purposive sampling, 27 service providers and community members with knowledge of
      the local context and the diverse needs of those at risk of depression were
      interviewed. 30% of participants were Indigenous. The proposed pathway to care
      was adapted in response to participant feedback. RESULTS: The study found that
      Indigenous mental health and well-being is perceived as multifaceted and strongly
      linked to cultural identity. It also confirms that there is broad support for
      promotion of a clear pathway to early intervention. Key identified components of
      this pathway were the health centre, visiting and community-based services, and
      local community resources including elders, cultural activities and families.
      Enablers to early intervention were reported. Significant barriers to the
      detection and treatment of those at risk of depression were identified, including
      insufficient resources, negative attitudes and stigma, and limited awareness of
      support options. CONCLUSIONS: Successful early intervention for well-being
      concerns requires improved understanding of Indigenous well-being perspectives
      and a systematic change in service delivery that promotes integration,
      flexibility and collaboration between services and the community, and recognises
      the importance of social determinants in health promotion and the healing
      process. Such changes require policy support, targeted training and education,
      and ongoing promotion.

PMID- 26316650
TI  - Development of a multivariable model to predict vulnerability in older American
      patients hospitalised with cardiovascular disease.
AB  - OBJECTIVES: To identify vulnerable cardiovascular patients in the hospital using
      a self-reported function-based screening tool. PARTICIPANTS: Prospective
      observational cohort study of 445 individuals aged >= 65 years admitted to a
      university medical centre hospital within the USA with acute coronary syndrome
      and/or decompensated heart failure. METHODS: Participants completed an inperson
      interview during hospitalisation, which included vulnerable functional status
      using the Vulnerable Elders Survey (VES-13), sociodemographic, healthcare
      utilisation practices and clinical patient-specific measures. A multivariable
      proportional odds logistic regression model examined associations between VES-13
      and prior healthcare utilisation, as well as other coincident medical and
      psychosocial risk factors for poor outcomes in cardiovascular disease. RESULTS:
      Vulnerability was highly prevalent (54%) and associated with a higher number of
      clinic visits, emergency room visits and hospitalisations (all p<0.001). A
      multivariable analysis demonstrating a 1-point increase in VES-13 (vulnerability)
      was independently associated with being female (OR 1.55, p=0.030), diagnosis of
      heart failure (OR 3.11, p<0.001), prior hospitalisations (OR 1.30, p<0.001), low
      social support (OR 1.42, p=0.007) and depression (p<0.001). A lower VES-13 score
      (lower vulnerability) was associated with increased health literacy (OR 0.70,
      p=0.002). CONCLUSIONS: Vulnerability to functional decline is highly prevalent in
      hospitalised older cardiovascular patients and was associated with patient risk
      factors for adverse outcomes and an increased use of healthcare services.

PMID- 26316651
TI  - Accuracy of administrative data for surveillance of healthcare-associated
      infections: a systematic review.
AB  - OBJECTIVE: Measuring the incidence of healthcare-associated infections (HAI) is
      of increasing importance in current healthcare delivery systems. Administrative
      data algorithms, including (combinations of) diagnosis codes, are commonly used
      to determine the occurrence of HAI, either to support within-hospital
      surveillance programmes or as free-standing quality indicators. We conducted a
      systematic review evaluating the diagnostic accuracy of administrative data for
      the detection of HAI. METHODS: Systematic search of Medline, Embase, CINAHL and
      Cochrane for relevant studies (1995-2013). Methodological quality assessment was
      performed using QUADAS-2 criteria; diagnostic accuracy estimates were stratified
      by HAI type and key study characteristics. RESULTS: 57 studies were included, the
      majority aiming to detect surgical site or bloodstream infections. Study designs
      were very diverse regarding the specification of their administrative data
      algorithm (code selections, follow-up) and definitions of HAI presence. One-third
      of studies had important methodological limitations including differential or
      incomplete HAI ascertainment or lack of blinding of assessors. Observed
      sensitivity and positive predictive values of administrative data algorithms for
      HAI detection were very heterogeneous and generally modest at best, both for
      within-hospital algorithms and for formal quality indicators; accuracy was
      particularly poor for the identification of device-associated HAI such as central
      line associated bloodstream infections. The large heterogeneity in study designs
      across the included studies precluded formal calculation of summary diagnostic
      accuracy estimates in most instances. CONCLUSIONS: Administrative data had
      limited and highly variable accuracy for the detection of HAI, and their
      judicious use for internal surveillance efforts and external quality assessment
      is recommended. If hospitals and policymakers choose to rely on administrative
      data for HAI surveillance, continued improvements to existing algorithms and
      their robust validation are imperative.

PMID- 26316652
TI  - Geospatial patterns of human papillomavirus vaccine uptake in Minnesota.
AB  - OBJECTIVES: To identify factors associated with human papillomavirus (HPV)
      vaccination and to determine the geographic distribution of vaccine uptake while
      accounting for spatial autocorrelation. DESIGN: This study is cross-sectional in
      design using data collected via the Internet from the Survey of Minnesotans About
      Screening and HPV study. SETTING AND PARTICIPANTS: The sample consists of 760
      individuals aged 18-30 years nested within 99 ZIP codes surrounding the downtown
      area of Minneapolis, Minnesota. RESULTS: In all, 46.2% of participants had
      received >= 1 dose of HPV vaccine (67.7% of women and 13.0% of men). Prevalence
      of HPV vaccination was found to exhibit strong spatial dependence ([Formula: see
      text] = 0.9951) across ZIP codes. Accounting for spatial dependence, age
      (OR=0.76, 95% CI 0.70 to 0.83) and male gender (OR=0.04, 95% CI 0.03 to 0.07)
      were negatively associated with vaccination, while liberal political preferences
      (OR=4.31, 95% CI 2.32 to 8.01), and college education (OR=2.58, 95% CI 1.14 to
      5.83) were found to be positively associated with HPV vaccination. CONCLUSIONS:
      Strong spatial dependence and heterogeneity of HPV vaccination prevalence were
      found across ZIP codes, indicating that spatial statistical models are needed to
      accurately identify and estimate factors associated with vaccine uptake across
      geographic units. This study also underscores the need for more detailed data
      collected at local levels (eg, ZIP code), as patterns of HPV vaccine receipt were
      found to differ significantly from aggregated state and national patterns. Future
      work is needed to further pinpoint areas with the greatest disparities in HPV
      vaccination and how to then access these populations to improve vaccine uptake.

PMID- 26316653
TI  - Prevalence of group A streptococcal disease in North and Sub-Saharan Africa: a
      systematic review protocol.
AB  - INTRODUCTION: The true burden of group A streptococcal (GAS) disease in Africa is
      not known. GAS is a significant cause of mortality and morbidity on the global
      scale and in developing countries. According to Carapetis et al, the prevalence
      of severe GAS disease is at least 18.1 million cases with an incidence of at
      least 1.78 million cases per year. METHODS AND ANALYSES: We aim to provide a
      systematic review of studies measuring the prevalence of GAS infection among
      people in North and Sub-Saharan African countries. A comprehensive literature
      search of a number of databases will be undertaken, using an African search
      filter, to identify GAS prevalence studies that have been published. Full copies
      of articles will be identified by a defined search strategy and will be
      considered for inclusion against predefined criteria. Statistical analysis will
      include two steps: (1) identification of data sources and documenting of
      estimates, and (2) the application of the random-effects and fixed-effects meta
      analysis model to aggregate prevalence estimates, and to account for between
      study variability in calculating the overall pooled estimates and 95% CI for GAS
      prevalence. Heterogeneity will be evaluated using the I(2) statistic to determine
      the extent of variation in effect estimates that is due to heterogeneity rather
      than chance. This systematic review protocol was prepared according to the
      Preferred Reporting Items for Systematic reviews and Meta-Analyses Protocols
      (PRISMA-P) 2015 Statement. This review will provide updated evidence of a review
      published in 2009. Our data will have implications for the development of a GAS
      vaccine. ETHICS AND DISSEMINATION: Ethics approval is not required for this study
      given that this is a protocol for a systematic review of published studies. The
      results of this study will be disseminated through a peer-reviewed publication
      and conference presentation. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO
      CRD4201401290 0.
      (http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42014012900).

PMID- 26316655
TI  - Conclusions Regarding Cross-Group Differences in Happiness Depend on Difficulty
      of Reaching Respondents.
AB  - A growing literature explores differences in subjective well-being across
      demographic groups, often relying on surveys with high nonresponse rates. By
      using the reported number of call attempts made to participants in the University
      of Michigan's Surveys of Consumers, we show that comparisons among easy-to-reach
      respondents differ from comparisons among hard-to-reach ones. Notably, easy-to
      reach women are happier than easy-to-reach men, but hard-to-reach men are happier
      than hard-to-reach women, and conclusions of a survey could reverse with more
      attempted calls. Better alternatives to comparing group sample averages might
      include putting greater weight on hard-to-reach respondents or even extrapolating
      trends in responses.

PMID- 26316654
TI  - A structured exercise programme during haemodialysis for patients with chronic
      kidney disease: clinical benefit and long-term adherence.
AB  - OBJECTIVE: Long-term studies regarding the effect of a structured physical
      exercise programme (SPEP) during haemodialysis (HD) assessing compliance and
      clinical benefit are scarce. STUDY DESIGN: A single-centre clinical trial, non
      randomised, investigating 46 patients with HD (63.2 +/- 16.3 years, male/female
      24/22, dialysis vintage 4.4 years) performing an SPEP over 5 years. The SPEP
      (twice/week for 60 min during haemodialysis) consisted of a combined resistance
      (8 muscle groups) and endurance (supine bicycle ergometry) training. Exercise
      intensity was continuously adjusted to improvements of performance testing.
      Changes in endurance and resistance capacity, physical functioning and quality of
      life (QoL) were analysed over 1 year in addition to long-term adherence and
      economics of the programme over 5 years. Average power per training session,
      maximal strength tests (maximal exercise repetitions/min), three performance
      based tests for physical function, SF36 for QoL were assessed in the beginning
      and every 6 months thereafter. RESULTS: 78% of the patients completed the
      programme after 1 year and 43% after 5 years. Participants were divided-
      according to adherence to the programme--into three groups: (1) high adherence
      group (HA, >80% of 104 training sessions within 12 months), (2) moderate
      adherence (MA, 60-80%), and 3. Low adherence group (LA, <60%)) with HA and MA
      evaluated quantitatively. One-year follow-up data revealed significant (p<0.05)
      improvement for both groups in all measured parameters: exercise capacity (HA:
      55%, MA: 45%), strength (HA: >120%, MA: 40-50%), QoL in three scores of SF36
      subscales and physical function in the three tests taken between 11% and 31%.
      Moreover, a quantitative correlation analysis revealed a close association
      (r=0.8) between large improvement of endurance capacity and weak physical
      condition (HA). CONCLUSIONS: The exercise programme described improves physical
      function significantly and can be integrated into a HD routine with a high long
      term adherence.

PMID- 26316656
TI  - Climate Change and Risk Projection: Dynamic Spatial Models of Tsetse and African
      Trypanosomiasis in Kenya.
AB  - African trypanosomiasis, otherwise known as sleeping sickness in humans and
      nagana in animals, is a parasitic protist passed cyclically by the tsetse fly.
      Despite more than a century of control and eradication efforts, the fly remains
      widely distributed across Africa and coextensive with other prevalent diseases.
      Control and planning are hampered by spatially and temporally variant vector
      distributions, ecologically irrelevant boundaries, and neglect. Tsetse are
      particularly well suited to move into previously disease-free areas under climate
      change scenarios, placing unprepared populations at risk. Here we present the
      modeling framework ATcast, which combines a dynamically downscaled regional
      climate model with a temporally and spatially dynamic species distribution model
      to predict tsetse populations over space and time. These modeled results are
      integrated with Kenyan population data to predict, for the period 2050 to 2059,
      exposure potential to tsetse and, by association, sleeping sickness and nagana
      across Kenya.

PMID- 26316657
TI  - Population dynamics: Social security, markets, and families.
AB  - Upward intergenerational flows - from the working ages to old age - are
      increasing substantially in the advanced industrialized countries and are much
      larger than in developing countries. Population aging is the most important
      factor leading to this change. Thus, in the absence of a major demographic shift,
      e.g., a return to high fertility, an increase in upward flows is inevitable. Even
      so, three other important factors will influence the magnitudes of upward flows.
      First, labor income varies at older ages due to differences in average age at
      retirement, productivity, unemployment, and hours worked. Second, the age
      patterns of consumption at older ages vary primarily due to differences in
      spending on health. Third, spending on human capital, i.e., spending child health
      and education, varies. Human capital spending competes with spending on the
      elderly, but it also increases the productivity of subsequent generations of
      workers and the resources available to support consumption in old age. All
      contemporary societies rely on a variety of institutions and economic mechanisms
      to shift economic resources from the working ages to the dependent ages - the
      young and the old. Three institutions dominate intergenerational flows:
      governments which implement social security, education, and other public transfer
      programs; markets which are key to the accumulation of assets, e.g., funded
      pensions and housing; and families which provide economic support to children in
      all societies and to the elderly in many. The objectives of this paper are,
      first, to describe how population aging and other changes influence the direction
      and magnitude of intergenerational flows; and, second, to contrast the
      institutional approaches to intergenerational flows as they are practiced around
      the world. The paper relies extensively on National Transfer Accounts, a system
      for measuring economic flows across age in a manner consistent with the UN System
      of National Accounts. These accounts are currently being constructed by research
      teams located in 33 countries on six continents representing wide variations in
      the level of development, demographics, and policies regarding intergenerational
      transfers.

PMID- 26316658
TI  - Improving the Measurement of Poverty.
AB  - This study estimates 2007 national poverty rates using an approach largely
      conceptualized by a 1995 National Academy of Sciences panel and similar to the
      supplemental poverty measure that will soon be produced by the U.S. Census
      Bureau. The study uses poverty thresholds based on expenditures for shelter,
      food, clothing, and utilities, as well as a measure of family income that
      includes earnings, cash transfers, near-cash benefits, tax credits, and tax
      payments. The measure also accounts for child care, work, and out-of-pocket
      medical expenses; variation in regional cost of living; and mortgage-free
      homeownership. Under this method, the rate of poverty is estimated to be higher
      than the rate calculated in the traditional manner, rising from 12.4 percent in
      the official measure to 16 percent in the new measure; the rate of child poverty
      is more than 3 percentage points higher, and elderly poverty is nearly 7 points
      higher.

PMID- 26316659
TI  - After-School Program for urban youth: Evaluation of a health careers course in
      New York City high schools.
AB  - Mentoring in Medicine (MIM) addresses an urgent national need for minority health
      professionals and promotes careers in health care for urban youth. The MIM After
      School Program (ASP or The Course) has as its primary objectives to provide
      academic enrichment in human biology and motivate disadvantaged youth to pursue a
      career in the health professions. Secondary objectives of The Course, although
      not evaluated here, are to improve students' health literacy and knowledge of
      healthy living behaviors. Since 2009, over 1500 middle and high school students
      have completed the New York City based Course, which is offered once a week over
      a 10 week semester in an out-of-school venue. This study assesses the success of
      The Course in achieving its primary objectives with 84 students at five New York
      City high schools during the fall 2014 semester. The Course curriculum was
      created especially for MIM, comprises the body's 11 organ systems, and is
      presented in discrete modules (one each semester), along with complementary
      educational activities, including field trips and class projects. This study
      reports on a formal evaluation using quantitative and qualitative methods. The
      quantitative evaluation found that the students significantly increased their
      knowledge of the Gastrointestinal System. Students across the academic spectrum
      appeared to have learned the MIM ASP Course content - high school GPA was not a
      predictor of knowledge acquisition. The students also reported that The Course
      significantly increased their self-confidence in their ability to succeed (self
      efficacy). The students expressed a significant increase in five health care
      related attitudes and an additional increase in their ability to overcome
      personal issues to succeed in their career and significantly improving their
      feeling toward, and likely pursuit of, a health career. The students stated that
      The Course significantly increased their interest and intent to seek out more
      information about health care, participate in health care activities, and take
      more health care courses in high school. The qualitative evaluation found that
      the students and their parents were pleased with the MIM ASP Course's
      composition, presentation, and effectiveness. With a large majority of the
      parents stating that their child got out of The Course what they had hoped for
      and that The Course made it more likely that they would recommend a health career
      for their child. The students and instructional staff also identified The Course
      elements that they felt were most and least effective. Best practices that were
      used in designing and conducting The Course were identified. The MIM ASP Course
      appears to have achieved its principal educational objectives of providing
      academic enrichment in human biology and improving attitudes towards a health
      career for a self-selected population of disadvantaged, underrepresented minority
      high school students in an urban setting.

PMID- 26316660
TI  - The Relationship between Genetic Attributions, Appraisals of Birth Mothers'
      Health, and the Parenting of Adoptive Mothers and Fathers.
AB  - Parenting beliefs and attributions can influence parenting behavior. We used an
      adoption design to examine the associations among perinatal risk and poor birth
      mother health, adoptive parent appraisals of birth mothers' mental health, and
      genetic attributions to adoptive parents' feelings and behaviors toward their
      adopted infants. A sample of 361 pairs of adoptive parents and birth mothers were
      interviewed using standardized measures when infants were between 4 and 9 months
      old. Adoptive mothers and fathers were observed during play tasks when their
      infants were 9 months old. We found that adoptive mothers' and fathers'
      appraisals of birth mothers' health were associated with perinatal risk and poor
      birth mother health. Adoptive mothers' appraisals were linked to hostile
      parenting, after accounting for characteristics of the child that may influence
      her appraisals and attributions. These associations were not present for adoptive
      fathers. Genetic attributions were associated with both adoptive mother and
      fathers' feelings of daily hassles in parenting. These findings have implications
      for prevention and intervention.

PMID- 26316662
TI  - Coronary Perforation Complicating Percutaneous Coronary Intervention - A Case
      Illustration and Review.
AB  - Coronary perforation is a potentially fatal complication during percutaneous
      coronary intervention (PCI). Reports have shown that it occurs in 0.2 to 0.6% of
      all patients undergoing the procedures. [1-3] Though the frequency of coronary
      perforation is low, it is a serious and potentially life-threatening situation
      that warrants prompt recognition and management. Here we illustrate a case of
      coronary perforation, and review the incidence, causes, clinical sequelae and
      management of coronary perforation in the current contemporary practice.

PMID- 26316663
TI  - Coronary Artery to Right Atrium Fistula Associated With First Degree
      Atrioventricular Block: A Rare Association.

PMID- 26316664
TI  - Thought Leadership on Thrombotic Disorders in South East Asia.
AB  - Thrombosis is a leading cause of morbidity and mortality, not only in aging
      industrialized countries, but also many emerging economies1.

PMID- 26316665
TI  - Opposition: Unfractionated heparin should no longer be used in the
      catheterization laboratory.
AB  - The goal of anticoagulation during percutaneous coronary intervention (PCI) is
      the primary and secondary prevention of thrombotic and significant bleeding
      events that increase cardiovascular morbidity and mortality. Unfractionated
      heparin is the most commonly-used anticoagulant, but low-molecular weight
      heparin, and more recently bivalirudin are becoming increasingly popular in
      cardiac catheterization laboratories1. The ACC/AHA/SCAI PCI guidelines2 recommend
      a 70-100 IU/kg bolus of heparin to achieve an activated clotting time (ACT) of
      250-300 seconds for Hemotec and 300-350 seconds for Hemochron systems, when
      glycoprotein IIb/IIIa inhibitors are not used. When glycoprotein IIb/IIIa
      inhibitors are used, a bolus of 50-70 IU/kg of unfractionated heparin is
      recommended to achieve an ACT of 200-250 seconds.

PMID- 26316666
TI  - Impact Of Sex On Clinical Characteristics And In-Hospital Outcomes In A Multi
      Ethnic Southeast Asian Population Of Patients Hospitalized For Acute Heart
      Failure.
AB  - OBJECTIVES: To study sex differences in clinical characteristics and outcomes
      among multi-ethnic Southeast Asian patients with hospitalized heart failure
      (HHF). BACKGROUND: HHF is an important public health problem affecting man and
      women globally. Reports from Western populations suggest striking sex differences
      in risk factors and outcomes in HHF. However, this has not been studied in a
      multi-ethnic Asian population. METHODS: Using the population-based resources of
      the Singapore Cardiac Data Bank, we studied 5,703 consecutive cases of HHF
      admitted across hospitals in the Southeast Asian nation of Singapore from 1st
      January, 2008 through 31st December, 2009. RESULTS: Women accounted for 46% of
      total admissions and were characterized by older age (73 vs. 67 years; p<0.001),
      higher prevalence of hypertension (78.6 vs. 72.1%; p<0.001) or atrial
      fibrillation (22.2 vs. 18.1%; p<0.001), and lower prevalence of coronary artery
      disease (33.8 vs. 41.0%; p<0.001) or prior myocardial infarction (14.9 vs. 19.8%;
      p<0.001). Women were more likely than men to have HHF with preserved ejection
      fraction (42.5% versus 20.8%, p < 0.001). Women were less likely than men to
      receive evidencebased therapies at discharge, both in the overall group and in
      the sub-group with reduced ejection fraction. Women had longer lengths of stay
      (5.6 vs. 5.1 days; p<0.001) but similar in-hospital mortality and one-year
      rehospitalization rates compared to men. Independent predictors of mortality or
      rehospitalization in both men and women included prior myocardial infarction and
      reduced ejection fraction. Among women alone, additional independent predictors
      were renal impairment, atrial fibrillation, and diabetes. Prescription of beta
      blockers and ACE-inhibitors at discharge was associated with better outcomes.
      CONCLUSION: Among multi-ethnic Asian patients with HHF, there are important sex
      differences in clinical characteristics and prognostic factors. These data may
      inform sex-specific strategies to improve outcomes of HHF in Southeast Asians.

PMID- 26316667
TI  - Risk factors for cardiovascular events among Asian patients without pre-existing
      cardiovascular disease on the renal transplant wait list.
AB  - INTRODUCTION: For suitable end-stage renal failure (ESRF) patients, renal
      transplantation gives better long term survival and quality of life as compared
      to dialysis. Prior to entry into the renal transplant wait list, potential
      candidates are screened for the presence of cardiovascular disease. However, the
      waiting time on the transplant list is long, and interval screening for cardiac
      fitness for surgery is not well defined. We aim to study the risk factors for the
      development of a cardiovascular event (CVE) and the time interval from
      recruitment to onset of a CVE that resulted in their removal from the transplant
      wait list. METHODS: A retrospective study of all patients registered under the
      cadaveric renal transplant waiting list in Singapore General Hospital (SGH) from
      16th April 1987 to 31st October 2010. We identified patients who developed a CVE
      among this cohort. We compared the demographics and clinical characteristics of
      patients who experienced a CVE versus those who did not. Univariable and
      multivariable cox regression were performed to investigate the significant
      variables for the development of a CVE. The time to development of CVE was
      estimated using Kaplan Meier estimation and log-rank test was used to compare the
      time to CVE between those with diabetes mellitus and those without. RESULTS: 1265
      patients were enrolled in this study. 273 patients dropped out of the wait list
      due to medical reasons or death, of which 38.8% were due to CVE. The mean and
      median time duration from recruitment into the waiting list to development of a
      CVE was 14.42 (95% CI 13.72 to 15.11) and 15.69 (95% CI 13.86 to 17.51) years
      respectively. For patients with diabetes mellitus, this was 8.22 (95% CI 6.30 to
      10.14) and 8.16 (95% CI 4.95 to 11.36) years respectively. Factors associated
      with an increased risk of developing a CVE included male gender (adjusted HR
      2.21, 95% CI 1.43 to 3.41, p<0.001), presence of diabetes mellitus (adjusted HR
      5.13, 95% CI 2.85 to 9.24, p<0.001) and patients who were either not working or
      working part-time as compared to their full-time counterparts (adjusted HR 1.76,
      95% CI 1.14 to 2.72, p=0.010). In addition, hazard ratio for CVE significantly
      increased with advancing age quartile (p<0.001 by log rank test for trend).
      CONCLUSION: A significant proportion of patients exited from the renal transplant
      wait list due to a CVE. Being male, age 37 years old or more, presence of
      diabetes mellitus and non-working or part-time workers as compared to full-time
      workers were found to increase the risk of developing a CVE during the wait
      period for transplantation. The presence of diabetes mellitus significantly
      shortened the time to development of a CVE.

PMID- 26316668
TI  - CNS active target (CAT) for missing mass spectroscopy with intense beams.
AB  - A new gaseous active target based on a time projection chamber, named CAT, is
      introduced. The remarkable feature is a dual gain THGEM to decrease the effective
      gain for the beam particles while keeping a high enough effective gain for the
      recoil particles. The measured effective gain of low gain region was a factor of
      one hundred smaller than that of high gain region. This technique provides a wide
      dynamic range in order to detect both the beam and recoil particles at the same
      time even with a very high intensity beam of more than 105 Hz.

PMID- 26316669
TI  - Molybdenum targets produced by mechanical reshaping.
AB  - Targets required to determine the parameters of the 100Mo(p,xn)99mTc reaction and
      to estimate the yield of the 99mTc production were prepared starting with powder
      material. Material, melted with electron beam gun into solid bead, was reshaped
      into foil mechanically. Targets were prepared by powder melting and hot
      flattening of the droplet followed by cold rolling. Procedure allowed preparation
      of thick (in the range of hundreds of microns) and thin (down to 250 nm) foils.

PMID- 26316670
TI  - Enumerating and indexing many-body intramolecular interactions: a graph theoretic
      approach.
AB  - The central idea observes a recursive mapping of [Formula: see text]-body
      intramolecular interactions to [Formula: see text]-body terms that is consistent
      with the molecular topology. Iterative application of the line graph
      transformation is identified as a natural and elegant tool to accomplish the
      recursion. The procedure readily generalizes to arbitrary [Formula: see text]
      body potentials. In particular, the method yields a complete characterization of
      [Formula: see text]-body interactions. The hierarchical structure of atomic index
      lists for each interaction order [Formula: see text] is compactly expressed as a
      directed acyclic graph. A pseudo-code description of the generating algorithm is
      given. With suitable data structures (e.g., edge lists or adjacency matrices),
      automatic enumeration and indexing of [Formula: see text]-body interactions can
      be implemented straightforwardly to handle large bio-molecular systems. Explicit
      examples are discussed, including a chemically relevant effective potential model
      of taurocholate bile salt.

PMID- 26316671
TI  - Investigation of pre-pubertal sex differences in wheel running and social
      behavior in three mouse strains.
AB  - Sex differences in social behaviors exist in mammals during adulthood, and
      further evidence suggests that sex differences in behavior are present before
      sexual maturity. In order to model behavioral disorders in animals, it is
      important to assess baseline sex-related behavioral differences, especially when
      studying disorders for which sex-related behavioral effects are expected. We
      investigated the effect of sex on behavior in 3 strains of pre-pubertal mice
      (C57BL/6, CFW, and CF1) using a wheel-running assay. We found no significant sex
      differences in latency to run on the wheel or total duration of wheel running
      within each strain. During the social interaction test, there were no differences
      between sexes in latency or total duration of contact or following between a
      subject and novel mouse. We also evaluated behavioral patterns of wheel running
      and stereotypical behaviors, such as burrowing and grooming. Both sexes showed
      characteristic wheel running behavior, spending the majority of each trial
      interacting with the wheel when it was free and more time performing other
      activities (e.g., stereotypical behaviors, general locomotion) when it was
      jammed. These results provide evidence that, among various strains of pre
      pubertal mice, baseline sex-related behavioral differences are not strong enough
      to influence the measured behaviors.

PMID- 26316672
TI  - Evolution of high-temperature molecular relaxations in poly(2-(2
      methoxyethoxy)ethyl methacrylate) upon network formation.
AB  - Copolymers of 2-(2-methoxyethoxy)ethyl methacrylate (poly(MEO2MA)) are regarded
      as bioinert replacements of poly(N-isopropylacrylamide) in some biomedical
      applications. Networks of poly(MEO2MA) of various architecture form thermo
      responsive hydrogels. Here, we present dielectric and mechanical spectroscopy
      studies on segmental motions and network relaxation processes in linear
      poly(MEO2MA) and its networks - bare network and the network grafted with short
      poly(MEO2MA) chains. We show that the alpha process assigned to the segmental
      motions of poly(MEO2MA) is independent on the polymer topology and the glass
      transition temperature, Tg, associated with this process equals 235-236 K for all
      investigated systems. The alpha' relaxation observed above Tg by dynamical
      mechanical analysis is assigned to the sub-Rouse process. It strongly depends on
      the polymer network architecture and slows down by four orders of magnitude upon
      network formation.

PMID- 26316673
TI  - Lecithin-based wet chemical precipitation of hydroxyapatite nanoparticles.
AB  - Hydroxyapatite Ca10(PO4)6(OH)2 nanoparticles have been successfully synthesized
      by the wet chemical precipitation method at 60  degrees C in the presence of
      biocompatible natural surfactant-lecithin. The composition and morphology of
      nanoparticles of hydroxyapatite synthesized with lecithin (nHAp-PC) was studied
      by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and
      scanning electron microscopy (SEM). Size distribution for nanoparticles was
      measured by nanoparticle tracking analysis in NanoSight system. We discuss in
      details influence of lecithin concentration in reaction system on nHAp-PC
      morphology, as well as on size distributions and suspendability of nanoparticles.
      Product exhibits crystalline structure and chemical composition of
      hydroxyapatite, with visible traces of lecithin. Difference in surfactant amounts
      results in changes in particles morphology and their average size.

PMID- 26316674
TI  - Dimensions of Subjective Well-Being.
AB  - We use two waves of a population based survey (the RAND American Life Panel) to
      investigate the relations between various evaluative and experienced well-being
      measures based on the English Longitudinal Study of Aging, the Gallup Wellbeing
      Index, and a 12-item hedonic well-being module of the Health and Retirement
      Study. In a randomized set-up we administered several versions of the survey with
      different response scales. Using factor analysis, we find that all evaluative
      measures load on the same factor, but the positive and negative experienced
      affect measures load on different factors. We find evidence of an effect of
      response scales on both the estimated number of underlying factors and their
      relations with demographics. We conclude that finer response scales allowing more
      nuanced answers offer more reliability. The relation of evaluative and
      experienced measures with demographics are very different; perhaps the most
      striking aspect is the lack of a consistent relation of experienced well-being
      measures with income, while evaluative well-being is strongly positively related
      with income.

PMID- 26316675
TI  - Sex Differences in Money Pathology in the General Population.
AB  - This study examined sex differences in money beliefs and behaviours. Over 100,000
      British participants completed two measures online, one of which assessed "money
      pathology" (Forman in Mind over money, Doubleday, Toronto, 1987), and the other
      four "money types", based on the emotional associations of money (Furnham et al.
      in Personal Individ Differ, 52:707-711, 2012). Nearly all measures showed
      significant sex differences with medium to large effect sizes, and with females
      exhibiting more "money pathology" than males. The biggest difference on the money
      types was on money being associated with generosity (money representing love)
      where men scored much lower than females, and autonomy (money representing
      freedom) where men scored higher than women. For men, more than women, money
      represented Power and Security. Men were more likely to be Hoarders while women
      did more emotional regulatory purchasing. Implications and limitations of this
      study are discussed.

PMID- 26316676
TI  - Mass Spectrometric Identification and Differentiation of Botulinum Neurotoxins
      through Toxin Proteomics.
AB  - Botulinum neurotoxins (BoNTs) cause the disease botulism, which can be lethal if
      untreated. There are seven known serotypes of BoNT, A-G, defined by their
      response to antisera. Many serotypes are distinguished into differing subtypes
      based on amino acid sequence and immunogenic properties, and some subtypes are
      further differentiated into toxin variants. Toxin characterization is important
      as different types of BoNT can respond differently to medical countermeasures for
      botulism, and characterization of the toxin can aid in epidemiologic and forensic
      investigations. Proteomic techniques have been established to determine the
      serotype, subtype, or toxin variant of BoNT. These techniques involve digestion
      of the toxin into peptides, tandem mass spectrometric (MS/MS) analysis of the
      peptides, and database searching to identify the BoNT protein. These techniques
      demonstrate the capability to detect BoNT and its neurotoxin-associated proteins,
      and differentiate the toxin from other toxins which are up to 99.9% identical in
      some cases. This differentiation can be accomplished from toxins present in a
      complex matrix such as stool, food, or bacterial cultures and no DNA is required.

PMID- 26316677
TI  - The method of solution of equations with coefficients that contain measurement
      errors, using artificial neural network.
AB  - This paper presents an algorithm for solving N-equations of N-unknowns. This
      algorithm allows to determine the solution in a situation where coefficients Ai
      in equations are burdened with measurement errors. For some values of Ai (where i
      = 1,..., N), there is no inverse function of input equations. In this case, it is
      impossible to determine the solution of equations of classical methods.

PMID- 26316678
TI  - NETWORK-REGULARIZED HIGH-DIMENSIONAL COX REGRESSION FOR ANALYSIS OF GENOMIC DATA.
AB  - We consider estimation and variable selection in high-dimensional Cox regression
      when a prior knowledge of the relationships among the covariates, described by a
      network or graph, is available. A limitation of the existing methodology for
      survival analysis with high-dimensional genomic data is that a wealth of
      structural information about many biological processes, such as regulatory
      networks and pathways, has often been ignored. In order to incorporate such prior
      network information into the analysis of genomic data, we propose a network-based
      regularization method for high-dimensional Cox regression; it uses an l1-penalty
      to induce sparsity of the regression coefficients and a quadratic Laplacian
      penalty to encourage smoothness between the coefficients of neighboring variables
      on a given network. The proposed method is implemented by an efficient coordinate
      descent algorithm. In the setting where the dimensionality p can grow
      exponentially fast with the sample size n, we establish model selection
      consistency and estimation bounds for the proposed estimators. The theoretical
      results provide insights into the gain from taking into account the network
      structural information. Extensive simulation studies indicate that our method
      outperforms Lasso and elastic net in terms of variable selection accuracy and
      stability. We apply our method to a breast cancer gene expression study and
      identify several biologically plausible subnetworks and pathways that are
      associated with breast cancer distant metastasis.

PMID- 26316679
TI  - Optimized Agrobacterium-mediated sorghum transformation protocol and molecular
      data of transgenic sorghum plants.
AB  - Agrobacterium-mediated sorghum transformation frequency has been enhanced
      significantly via medium optimization using immature embryos from sorghum variety
      TX430 as the target tissue. The new transformation protocol includes the addition
      of elevated copper sulfate and 6-benzylaminopurine in the resting and selection
      media. Using Agrobacterium strain LBA4404, the transformation frequency reached
      over 10% using either of two different selection marker genes, moPAT or PMI, and
      any of three different vectors in large-scale transformation experiments. With
      Agrobacterium strain AGL1, the transformation frequencies were as high as 33%.
      Using quantitative PCR analyses of 1,182 T0 transgenic plants representing 675
      independent transgenic events, data was collected for T-DNA copy number, intact
      or truncated T-DNA integration, and vector backbone integration into the sorghum
      genome. A comparison of the transformation frequencies and molecular data
      characterizing T-DNA integration patterns in the transgenic plants derived from
      LBA4404 versus AGL1 transformation revealed that twice as many transgenic high
      quality events were generated when AGL1 was used compared to LBA4404. This is the
      first report providing molecular data for T-DNA integration patterns in a large
      number of independent transgenic plants in sorghum.

PMID- 26316680
TI  - An improved embryo-rescue protocol for hybrid progeny from seedless Vitis
      vinifera grapes * wild Chinese Vitis species.
AB  - A highly efficient technique of embryo rescue is critical when using
      stenospermocarpic Vitis vinifera cultivars (female parents) to breed novel,
      disease-resistant, seedless grape cultivars by hybridizing with wild Chinese
      Vitis species (male parents) having many disease-resistance alleles. The effects
      of various factors on the improvement of embryo formation, germination, and
      plantlet development for seven hybrid combinations were studied. The results
      indicated that Beichun and Shuangyou were the best male parents. The best
      sampling time for ovule inoculation differed among the female parents. When
      hybrid ovules were cultured on a double-phase medium with five different solid
      medium types, percent embryo formation was highest (11.3-28.3%) on a modified MM3
      medium. Percentages of embryo germination (15.4-55.4%) and plantlet development
      (11.15-44.6%) were all highest when embryos were cultured on Woody Plant Medium +
      5.7 MUM indole-3-acetic acid + 4.4 MUM 6-benzylaminopurine + 1.4 MUM gibberellic
      acid + 2% sucrose + 0.05% casein hydrolysate + 0.3% activated charcoal + 0.7%
      agar. In the absence of other amino acids, the addition of proline significantly
      increased embryo formation (36.1%), embryo germination (64.6%), and plantlet
      development (90.5%). A highly efficient protocol has been developed for hybrid
      embryo rescue from seedless V. vinifera grapes * wild Chinese Vitis species that
      results in a significant improvement in breeding efficiency for new disease
      resistant seedless grapes.

PMID- 26316681
TI  - Multiple Family Group Service Model for Children With Disruptive Behavior
      Disorders: Child Outcomes at Post-Treatment.
AB  - The purpose of this study was to determine the benefits of a multiple family
      group (MFG) service delivery model compared with services as usual (SAU) in
      improving the functioning of youth with oppositional defiant/conduct disorder in
      families residing in socioeconomically disadvantaged communities. Participants
      included 320 youth aged 7 to 11 and their families who were referred to
      participating outpatient clinics. Participants were assigned to the MFG or the
      SAU condition, with parent report of child oppositional behavior, social
      competence, and level of youth impairment as primary outcomes at post-treatment.
      Family engagement to MFG was measured by attendance to each group session.
      Caregivers of youth in the MFG service delivery model condition reported
      significant improvement in youth oppositional behavior and social competence
      compared with youth in the SAU condition. Impairment improved over time for both
      groups with no difference between treatment conditions. The MFG led to greater
      percentage of youth with clinically significant improvements in oppositional
      behavior. Attendance to the MFG was high, given the high-risk nature of the study
      population. The MFG service delivery model offers an efficient and engaging
      format to implement evidence-based approaches to improving functioning of youth
      with oppositional defiant and/or conduct disorder in families from
      socioeconomically disadvantaged communities.

PMID- 26316682
TI  - A Prototype Detector for a Novel High-Resolution PET System: BazookaPET.
AB  - We have designed and are developing a novel proof-of-concept PET system called
      BazookaPET. In order to complete the PET configuration, at least two detector
      elements are required to detect positron-electron annihilation events. Each
      detector element of the BazookaPET has two independent data acquisition channels.
      One side of the scintillation crystal is optically coupled to a 4*4 silicon
      photomultiplier (SiPM) array and the other side is a CCD-based gamma camera.
      Using these two separate channels, we can obtain data with high energy, temporal
      and spatial resolution data by associating the data outputs via several maximum
      likelihood estimation (MLE) steps. In this work, we present the concept of the
      system and the prototype detector element. We focus on characterizing individual
      detector channels, and initial experimental calibration results are shown along
      with preliminary performance-evaluation results. We measured energy resolution
      and the integrated traces of the slit-beam images from both detector channel
      outputs. A photo-peak energy resolution of ~5.3% FWHM was obtained from the SiPM
      and ~48% FWHM from the CCD at 662 keV. We assumed SiPM signals follow Gaussian
      statistics and estimated the 2D interaction position using MLE. Based on our the
      calibration experiments, we computed the Cramer-Rao bound (CRB) for the SiPM
      detector channel and found that the CRB resolution is better than 1 mm in the
      center of the crystal.

PMID- 26316683
TI  - Visual recovery following open globe injury with initial no light perception.
AB  - BACKGROUND: The purpose of this study was to analyze eyes presenting with no
      light perception (NLP) after open globe injury (OGI) to determine visual outcomes
      and prognostic indicators for visual recovery. METHODS: The records of
      consecutive patients with at least 6 months of follow-up presenting with OGI and
      NLP to a single institution between January 1, 2003 and December 31, 2013 were
      reviewed for demographics, ophthalmic history, context and characteristics of
      injury, ocular examination findings, surgical interventions, and follow-up visual
      acuity. Unpaired t-tests and Fisher's Exact tests were used for statistical
      analysis. RESULTS: Twenty-five patients met our inclusion criteria. The mean age
      was 50.4+/-25.5 (range 8-91) years. Four patients (16%) regained vision (hand
      motion in three patients and light perception in one patient) while 21 patients
      (84%) remained with NLP or had a prosthesis at final follow-up. Fourteen eyes
      (56%) were enucleated; nine (36%) were secondary enucleations. Although the
      sample sizes were small, neither ocular trauma score nor wound size was found to
      predict visual recovery. CONCLUSION: Four patients regained some vision after
      presenting with NLP due to OGI. These findings suggest that, in select cases,
      physicians should discuss the possibility of regaining some vision.

PMID- 26316684
TI  - Oral mineralocorticoid antagonists for recalcitrant central serous
      chorioretinopathy.
AB  - PURPOSE: To evaluate the effect and tolerance of oral mineralocorticoid
      antagonists, eplerenone and/or spironolactone, in recalcitrant central serous
      chorioretinopathy. METHODS: Retrospective consecutive observational case series.
      Primary outcome measures included central macular thickness (CMT, MUm), macular
      volume (MV, mm(3)), Snellen visual acuity, and prior treatment failures.
      Secondary outcomes included duration of treatment, treatment dosage, and systemic
      side effects. RESULTS: A total of 120 patients with central serous
      chorioretinopathy were reviewed, of which 29 patients were treated with one or
      more mineralocorticoid antagonists. The average age of patients was 58.4 years.
      Sixteen patients (69.6%) were recalcitrant to other interventions prior to
      treatment with oral mineralocorticoid antagonists, with an average washout period
      of 15.3 months. The average duration of mineralocorticoid antagonist treatment
      was 3.9+/-2.3 months. Twelve patients (52.2%) showed decreased CMT and MV, six
      patients (26.1%) had increase in both, and five patients (21.7%) had negligible
      changes. The mean decrease in CMT of all patients was 42.4 MUm (range, -136 to
      255 MUm): 100.7 MUm among treatment-naive patients, and 16.9 MUm among
      recalcitrant patients. The mean decrease in MV of all patients was 0.20 mm(3)
      (range, -2.33 to 2.90 mm(3)): 0.6 mm(3) among treatment-naive patients, and 0.0
      mm(3) among recalcitrant patients. Median visual acuity at the start of therapy
      was 20/30 (range, 20/20-20/250), and at final follow-up it was 20/40 (range,
      20/20-20/125). Nine patients (39.1%) experienced systemic side effects, of which
      three patients (13.0%) were unable to continue therapy. CONCLUSION:
      Mineralocorticoid antagonist treatment had a positive treatment effect in half of
      our patients. The decrease in CMT and MV was much less in the recalcitrant group
      compared to the treatment-naive group. An improvement in vision was seen only in
      the treatment-naive group. Systemic side effects, even at low doses, may limit
      its usage in some patients.

PMID- 26316685
TI  - Portable single port 23-gauge vitrectomy in postoperative endophthalmitis.
AB  - AIM: To evaluate the safety and effectiveness of the Intrector((r)) for treating
      postoperative endophthalmitis. MATERIALS AND METHODS: In a retrospective
      multicenter study, patients who received a single port 23-gauge core pars plana
      vitrectomy and isovolumetric injection of vancomycin, ceftazidime, and
      dexamethasone/amphotericin B using the Intrector((r)) for postoperative
      endophthalmitis of intermediate severity (grade II or III vitreous inflammation
      and best-corrected visual acuity between hand movements and 0.3 logMAR [logarithm
      of the minimum angle of resolution]) were evaluated. Improvement in visual
      acuity, resolution of intraocular inflammation, the need for additional surgical
      procedures, and the development of complications were evaluated at a 1-month
      follow-up examination. RESULTS: Fifteen patients (mean age 55.6+/-7.2 years)
      underwent treatment with the Intrector((r)). The mean vitreous volume aspirated
      was 0.78+/-0.22 mL. The vitreous samples indicated positive microorganism culture
      results in six of the 15 cases, but the samples were positive when analyzed by
      real-time polymerase chain reaction in all cases (15/15). The mean best-corrected
      visual acuity improved significantly (P=0.01) from 0.88+/-0.29 (logMAR) to 0.32+/
      0.28. Each patient demonstrated at least three lines of visual improvement. No
      additional medical or surgical interventions were required, and the complete
      resolution of intraocular inflammation was noted in all patients at the 1-month
      follow-up examination. No procedure-related complications were observed.
      CONCLUSION: The Intrector((r)) may be a safe and effective treatment option for
      infectious postoperative endophthalmitis. Larger studies comparing the outcomes
      of the Intrector((r)) to the traditional treatments for postoperative
      endophthalmitis need to be conducted before its role in the treatment of
      postoperative endophthalmitis can be properly defined.

PMID- 26316686
TI  - Combined eye gel containing sodium hyaluronate and xanthan gum for the treatment
      of the corneal epithelial defect after pterygium surgery.
AB  - AIM: The aim of this study is to compare the effectiveness of the ophthalmic gels
      containing hyaluronate, xanthan gum, and netilmycine with fusidic acid in terms
      of recovery periods of corneal epithelium in the patients who underwent pterygium
      surgery. METHODS: Patients who underwent pterygium surgery were separated into
      two groups. Forty patients in group 1 were given eye gel containing sodium
      hyaluronate, xanthan gum, and netilmycine, and 40 patients in group 2 were given
      one drop of eye gel containing fusidic acid. The patients in both groups were
      examined at the 12th, 24th, and 48th hours in the postoperative period by using
      slit-lamp technique. The subjective complaints of the patients such as pain and
      stinging, and the recovery periods of the corneal epithelial defect were
      evaluated comparatively by fluorescein staining. RESULTS: The mean ages were 26+/
      8 years (range: 18-35) and 24+/-6 years (range: 18-33) in groups 1 and 2,
      respectively. The closure period of the corneal epithelial defect was observed as
      24+/-8 hours (range: 16-42) and 36+/-12 hours (range: 18-48) in groups 1 and 2,
      respectively. The number of the patients suffering from subjective complaints
      such as pain and stinging in the first 12 hours was six and 29 in groups 1 and 2,
      respectively. The difference was significant both clinically and statistically
      (P=0.001). CONCLUSION: Combined eye gel containing hyaluronate, xanthan gum, and
      netilmycine accelerates the recovery of corneal epithelial defect and reduces the
      complaints of the patients, when compared to the fusidic acid gel. Combined eye
      gel should be considered as an option for the treatment of the corneal epithelial
      defect related with pterygium surgery.

PMID- 26316688
TI  - Erratum: Comparison of cumulative dissipated energy between the Infiniti and
      Centurion phacoemulsification systems [Corrigendum].
AB  - [This corrects the article on p. 1367 in vol. 9, PMID: 26229430.]. 

PMID- 26316687
TI  - Radial fundus autofluorescence in the periphery in patients with X-linked
      retinitis pigmentosa.
AB  - PURPOSE: To describe the peripheral autofluorescence images and clinical features
      of patients with retinal dystrophy who showed radial fundus autofluorescence
      (FAF) at the posterior pole. METHODS: The authors retrospectively reviewed pooled
      wide-field FAF images of 711 patients with retinal dystrophy and 56 family
      members. RESULTS: Eleven eyes of seven women exhibited radial FAF at the
      posterior pole. Wide-field FAF showed extension of the radial pattern to the
      periphery in all eyes except one. One woman showed radial hyper-FAF only in the
      periphery, not at the posterior pole. These eight individuals were X-linked
      retinitis pigmentosa patients or carriers. The tapetal-like reflex was not
      observed in their color fundus photographs. The peripheral visual field showed
      wedge-shaped restriction in some individuals. CONCLUSION: Wide-field FAF imaging
      can depict radial FAF not only at the posterior pole but also in the periphery in
      X-linked retinitis pigmentosa carriers. The authors therefore agree with previous
      reports that radial FAF may be a hallmark of X-linked retinitis pigmentosa.

PMID- 26316689
TI  - Noninfectious uveitis: strategies to optimize treatment compliance and adherence.
AB  - Noninfectious uveitis includes a heterogenous group of sight-threatening ocular
      and systemic disorders. Significant progress has been made in the treatment of
      noninfectious uveitis in recent years, particularly with regard to the effective
      use of corticosteroids and non-corticosteroid immunosuppressive drugs, including
      biologic agents. All of these therapeutic approaches are limited, however, by any
      given patient's ability to comply with and adhere to their prescribed treatment.
      In fact, compliance and adherence are among the most important patient-related
      determinants of treatment success. We discuss strategies to optimize compliance
      and adherence. 

PMID- 26316690
TI  - The correlation between visual acuity outcomes and optical coherence tomography
      parameters following surgery for diabetic epiretinal membrane and taut posterior
      hyaloid.
AB  - PURPOSE: To evaluate the relationship between visual outcomes and the
      determinants detected by spectral domain optical coherence tomography (OCT) in
      eyes with epiretinal membrane (ERM) and/or taut posterior hyaloid (TPH) that
      underwent pars plana vitrectomy (PPV). MATERIALS AND METHODS: A total of 30
      participants with diabetic ERM and TPH were included in the study. All study
      participants underwent PPV. Preoperative and postoperative best corrected visual
      acuity (BCVA), peripapillary retinal nerve fiber layer (RNFL), macular RNFL,
      ganglion cell layer, inner plexiform layer, and ganglion cell complex thicknesses
      were measured in each participant. Linear regression analyses were performed to
      determine the association between the OCT parameters and the visual acuity
      measured at the time of the OCT measurement. RESULTS: The postoperative BCVA
      logarithm of the minimum angle of resolution (logMAR) values were statistically
      higher than the preoperative values in the ERM group and TPH group (P=0.001 and
      P<0.001, respectively). The postoperative BCVA logMAR value was negatively
      correlated with average RNFL, inferior RNFL thicknesses, and image quality
      (P=0.002, P=0.004, and P=0.006, respectively). The preoperative and postoperative
      BCVA logMAR value difference was not correlated with age and all of the OCT
      parameters measured (P>0.05). CONCLUSION: This study shows that achievement of
      better peripapillary RNFL thickness results in better visual outcome after PPV
      and ERM/TPH removal.

PMID- 26316691
TI  - Indications and postoperative treatment for Ex-PRESS((r)) insertion in Japanese
      patients with glaucoma: comparison with standard trabeculectomy.
AB  - BACKGROUND: We investigated indications and early postoperative treatment for Ex
      PRESS((r)) insertion for glaucoma by comparing postoperative outcomes with those
      for standard trabeculectomy. METHODS: Ex-PRESS insertion was performed in 21 eyes
      and standard trabeculectomy (TLE) in 22 eyes. Mean intraocular pressure (IOP) in
      the 6 months after surgery, success rate for postoperative IOP decline,
      postoperative complications, postoperative treatment, filtering blebs, and
      indications were then retrospectively investigated. RESULTS: Mean postoperative
      IOP did not differ significantly between the groups at any observation time for 6
      months after surgery. Further, it did not differ between either the groups of
      patients with primary open-angle glaucoma (POAG) and neovascular glaucoma (NTG),
      or the patients with primary open-angle glaucoma and NTG in the Ex-PRESS group.
      Comparison of success rates in reduction of postoperative IOP between the groups
      under the following four survival conditions showed no significant differences:
      postoperative IOP <30% of the preoperative IOP, complete success (no additional
      ophthalmic solution), and qualified success (ophthalmic solution required); 5
      mmHg <= postoperative IOP <=21 mmHg, complete success (no additional ophthalmic
      solution), and qualified success (ophthalmic solution required). With regard to
      postoperative complications and postoperative treatment, the incidence of hyphema
      was significantly lower in the Ex-PRESS group, but no other significant
      intergroup differences were seen. The height of the filtering bleb was lower in
      the Ex-PRESS group. CONCLUSION: Postoperative outcomes in the Ex-PRESS and TLE
      groups were comparable. The incidence of hyphema was significantly lower in the
      Ex-PRESS group. Ex-PRESS insertion appears to be useful in patients with NTG and
      in those prone to postoperative bleeding. There were no significant intergroup
      differences in postoperative treatment. Assessment of outcome after Ex-PRESS
      insertion was difficult in some patients. Postoperative treatment should be
      developed to suit the specific requirements of Ex-PRESS insertion.

PMID- 26316692
TI  - Scotoma analysis of 10-2 visual field testing with a red target in screening for
      hydroxychloroquine retinopathy.
AB  - OBJECTIVE: To quantify the variability of scotomas detected by 10-2 visual field
      (VF) testing with a red target in patients taking hydroxychloroquine without and
      with retinopathy. DESIGN: Retrospective review of clinical charts and VFs.
      METHODS: Twenty-four patients taking hydroxychloroquine without retinopathy, and
      eight patients taking hydroxychloroquine with retinopathy were tested in this
      study. Retinopathy was defined by annular scotomas on 10-2 VF testing with
      corroborative spectral domain optical coherence tomographic outer retinal changes
      and multifocal electroretinographic changes leading to cessation of
      hydroxychloroquine or chloroquine. Location and depth of scotoma points on 10-2
      VF testing were recorded and their fates followed in serial, reliable 10-2 VFs
      performed with a red target over time. The main outcome measures for this study
      were the number of scotoma points and locations, percentage of persistent scotoma
      points, size of scotomas, location of scotomas, and percentage of scotomas
      deepening. RESULTS: A median of 3, interquartile range (IQR) (2, 5), scotoma
      points per VF occurred in patients without retinopathy. A median of 86%, IQR (77,
      100), of these resolved on the subsequent field. For patients with retinopathy, a
      median of 50%, IQR (46, 79), resolved, a difference compared to patients without
      retinopathy that was significant (P=0.0158). The median percentage of scotoma
      points in the zone from 2 degrees  to 8 degrees  from fixation in eyes with
      retinopathy was 72%, IQR (54, 100), compared to 49%, IQR (40, 54), in eyes
      without retinopathy (P=0.0069). The number of persistent scotoma locations at the
      last visit was higher in eyes with retinopathy: 3, IQR (1, 3), versus 0, IQR (0,
      1), in patients without retinopathy, P=0.0156. CONCLUSION: Point scotomas are
      common and variable in 10-2 VF testing with a red target for hydroxychloroquine
      retinopathy in subjects without retinopathy. Scotoma points in eyes with
      retinopathy are less variable. The annular zone 2 degrees -8 degrees  from
      fixation was useful for distinguishing the significance of scotoma points.
      Discriminating eyes with retinopathy from eyes without retinopathy is probably
      easier using the 10-2 VF with a white target than a red target.

PMID- 26316693
TI  - Refractive cylinder outcomes after calculating toric intraocular lens cylinder
      power using total corneal refractive power.
AB  - PURPOSE: To determine whether the total corneal refractive power (TCRP) value,
      which is based on measurement of both anterior and posterior corneal astigmatism,
      is effective for toric intraocular lens (IOL) calculation with AcrySof((r)) Toric
      IOLs. PATIENTS AND METHODS: A consecutive series of cataract surgery cases with
      AcrySof toric IOL implantation was studied retrospectively. The IOLMaster((r))
      was used for calculation of IOL sphere, the Pentacam((r)) TCRP 3.0 mm apex/ring
      value was used as the keratometry input to the AcrySof Toric IOL Calculator and
      the VERIONTM Digital Marker for surgical orientation. The keratometry readings
      from the VERION reference unit were recorded but not used in the actual
      calculation. Vector differences between expected and actual residual refractive
      cylinder were calculated and compared to simulated vector errors using the
      collected VERION keratometry data. RESULTS: In total, 83 eyes of 56 patients were
      analyzed. Residual refractive cylinder was 0.25 D or lower in 58% of eyes and 0.5
      D or lower in 80% of eyes. The TCRP-based calculation resulted in a statistically
      significantly lower vector error (P<0.01) and significantly more eyes with a
      vector error <=0.5 D relative to the VERION-based calculation (P=0.02). The TCRP
      and VERION keratometry readings suggested a different IOL toric power in 53/83
      eyes. In these 53 eyes the TCRP vector error was lower in 28 cases, the VERION
      error was lower in five cases, and the error was equal in 20 cases. When the
      anterior cornea had with-the-rule astigmatism, the VERION was more likely to
      suggest a higher toric power and when the anterior cornea had against-the-rule
      astigmatism, the VERION was less likely to suggest a higher toric power.
      CONCLUSION: Using the TCRP keratometry measurement in the AcrySof toric
      calculator may improve overall postoperative refractive results. Consideration of
      measured posterior corneal astigmatism, rather than a population-averaged value,
      appears advantageous.

PMID- 26316694
TI  - Synthesis, antimicrobial and in vitro antitumor activities of a series of 1,2,3
      thiadiazole and 1,2,3-selenadiazole derivatives.
AB  - Three derivatives of substituted 1,2,3-thia- or 1,2,3-selenadiazole (4a-c) were
      prepared and characterized by different chemical techniques. These compounds were
      evaluated for their antimicrobial and antitumor activities. Compounds 4a
      (propenoxide derivative), 4b (carbaldehyde derivative), and 4c (benzene
      derivative) were active against the yeast-like fungi Candida albicans. Compound
      4a was active against gram-negative Escherichia coli, and compound 4c was active
      against the gram-positive Staphylococcus aureus. For the antitumor activity, both
      compounds 4b and 4c were active against all tested tumor cell lines, namely,
      SW480, HCT116, C32, MV3, HMT3522, and MCF-7. The activity of compound 4c was
      greater than that of compound 4b and more than that of the reference antitumor 5
      flourouracil against the SW480, HCT116, and MCF-7 tumor cell lines. In
      conclusion, a number of the prepared 1,2,3-thia- or 1,2,3-selenadiazole compounds
      showed promising antifungal, antibacterial, and in vitro antitumor activities.
      Further investigations are required to explore the mechanism by which active
      compound are inducing their cytotoxicity. 

PMID- 26316695
TI  - Nutrigenomic effects of edible bird's nest on insulin signaling in ovariectomized
      rats.
AB  - Estrogen deficiency alters quality of life during menopause. Hormone replacement
      therapy has been used to improve quality of life and prevent complications, but
      side effects limit its use. In this study, we evaluated the use of edible bird's
      nest (EBN) for prevention of cardiometabolic problems in rats with ovariectomy
      induced menopause. Ovariectomized female rats were fed for 12 weeks with normal
      rat chow, EBN, or estrogen and compared with normal non-ovariectomized rats.
      Metabolic indices (insulin, estrogen, superoxide dismutase, malondialdehyde, oral
      glucose tolerance test, and lipid profile) were measured at the end of the
      experiment from serum and liver tissue homogenate, and transcriptional levels of
      hepatic insulin signaling genes were measured. The results showed that
      ovariectomy worsened metabolic indices and disrupted the normal transcriptional
      pattern of hepatic insulin signaling genes. EBN improved the metabolic indices
      and also produced transcriptional changes in hepatic insulin signaling genes that
      tended toward enhanced insulin sensitivity, and glucose and lipid homeostasis,
      even better than estrogen. The data suggest that EBN could meliorate estrogen
      deficiency-associated increase in risk of cardiometabolic disease in rats, and
      may in fact be useful as a functional food for the prevention of such a problem
      in humans. The clinical validity of these findings is worth studying further. 

PMID- 26316696
TI  - Advances in cancer pain from bone metastasis.
AB  - With the technological advances in cancer diagnosis and treatment, the survival
      rates for patients with cancer are prolonged. The issue of figuring out how to
      improve the life quality of patients with cancer has become increasingly
      prominent. Pain, especially bone pain, is the most common symptom in malignancy
      patients, which seriously affects the life quality of patients with cancer. The
      research of cancer pain has a breakthrough due to the development of the animal
      models of cancer pain in recent years, such as the animal models of mouse femur,
      humerus, calcaneus, and rat tibia. The establishment of several kinds of animal
      models related to cancer pain provides a new platform in vivo to investigate the
      molecular mechanisms of cancer pain. In this review, we focus on the advances of
      cancer pain from bone metastasis, the mechanisms involved in cancer pain, and the
      drug treatment of cancer pain in the animal models. 

PMID- 26316697
TI  - Ceftobiprole for the treatment of pneumonia: a European perspective.
AB  - Ceftobiprole, a new broad spectrum, parenteral cephalosporin, exhibits potent in
      vitro activity against a number of Gram-positive pathogens, including methicillin
      resistant Staphylococcus aureus and penicillin-resistant Streptococcus
      pneumoniae, and Gram-negative pathogens associated with hospital-acquired
      pneumonia (HAP) and community-acquired pneumonia (CAP). Ceftobiprole has
      demonstrated noninferiority in two large-scale pivotal studies comparing it to
      ceftriaxone with or without linezolid in CAP, with clinical cure rates 86.6%
      versus 87.4%, or ceftazidime in HAP, with clinical cure rates of 77% versus 76%,
      respectively. However, ceftobiprole was inferior in the subgroup of patients
      undergoing mechanical ventilation. Ceftobiprole has so far demonstrated a good
      safety profile in preliminary studies, with similar tolerability to comparators.
      The most commonly observed adverse events of ceftobiprole included headache and
      gastrointestinal upset. It is the first cephalosporin monotherapy approved in the
      EU for the treatment of both CAP and HAP (excluding ventilator-associated
      pneumonia). 

PMID- 26316698
TI  - Pooled post hoc analysis of population pharmacokinetics of oxycodone and
      acetaminophen following a single oral dose of biphasic immediate-release/extended
      release oxycodone/acetaminophen tablets.
AB  - This analysis evaluated the single-dose population pharmacokinetics (PK) of
      biphasic immediate-release (IR)/extended-release (ER) oxycodone
      (OC)/acetaminophen (APAP) 7.5/325 mg tablets administered under fasted conditions
      and the effects of a meal on their single-dose population PK. Data were pooled
      from four randomized, single-dose crossover trials enrolling healthy adult (18-55
      years old) participants (three trials) and nondependent recreational users of
      prescription opioids (one trial) with a body weight of >=59 kg. Participants
      received IR/ER OC/APAP 7.5/325 mg tablets in single doses of 7.5/325 mg (one
      tablet), 15/650 mg (two tablets), or 30/1,300 mg (four tablets) under fasted or
      fed conditions. Six variables were examined: sex, race, age, weight, height, and
      body mass index. Single-dose population PK was analyzed using first-order
      conditional estimation methods. A total of 151 participants were included in the
      analysis under fasted conditions, and 31 participants were included in the fed
      analysis. Under fasted conditions, a 10% change in body weight was accompanied by
      ~7.5% change in total body clearance (CL/F) and volume of distribution (V/F) of
      OC and APAP. Black participants had 17.3% lower CL/F and a 16.9% lower V/F of OC
      compared with white participants. Under fed conditions, the absorption rate
      constant of OC and APAP decreased significantly, although there was no effect on
      CL/F and V/F. Considering that the recommended dose for IR/ER OC/APAP 7.5/325 mg
      tablets is two tablets every 12 hours, adjustments of <50% are not clinically
      relevant. Dose adjustment may be necessary for large deviations from average body
      weight, but the small PK effects associated with race and consumption of a meal
      are not clinically relevant. 

PMID- 26316699
TI  - Relaxin inhibits cardiac fibrosis and endothelial-mesenchymal transition via the
      Notch pathway.
AB  - BACKGROUND: Relaxin (RLX) can prevent cardiac fibrosis. We aimed to investigate
      the possible mechanism and signal transduction pathway of RLX inhibiting cardiac
      fibrosis. METHODS: Isoproterenol (5 mg.kg(-1).d(-1)) was used to establish the
      cardiac fibrosis model in rats, which were administered RLX. The cardiac
      function, related targets of cardiac fibrosis, and endothelial-mesenchymal
      transition (EndMT) were measured. Transforming growth factor beta (TGF-beta) was
      used to induce EndMT in human umbilical vein endothelial cells, which were
      pretreated with RLX, 200 ng.mL(-1), then with the inhibitor of Notch. Transwell
      cell migration was used to evaluate cell migration. CD31 and vimentin content was
      determined by immunofluorescence staining and Western blot analysis. Notch
      protein level was examined by Western blot analysis. RESULTS: RLX improved
      cardiac function in rats with cardiac fibrosis; it reduced the content of
      collagen I and III, increased the microvascular density of the myocardium, and
      suppressed the EndMT in heart tissue. In vitro, RLX decreased the mobility of
      human umbilical vein endothelial cells induced by TGF-beta, increased the
      expression of endothelial CD31, and decreased vimentin content. Compared to TGF
      beta and RLX co-culture alone, TGF-beta + RLX + Notch inhibitor increased cell
      mobility and the EndMT, but decreased the levels of Notch-1, HES-1, and Jagged-1
      proteins. CONCLUSION: RLX may inhibit the cardiac fibrosis via EndMT by Notch
      mediated signaling.

PMID- 26316700
TI  - RGD-modified liposomes enhance efficiency of aclacinomycin A delivery: evaluation
      of their effect in lung cancer.
AB  - In this study, long-circulating Arg-Gly-Asp (RGD)-modified aclacinomycin A (ACM)
      liposomes were prepared by thin film hydration method. Their morphology, particle
      size, encapsulation efficiency, and in vitro release were investigated. The RGD
      ACM liposomes was about 160 nm in size and had the visual appearance of a
      yellowish suspension. The zeta potential was -22.2 mV and the encapsulation
      efficiency was more than 93%. The drug-release behavior of the RGD-ACM liposomes
      showed a biphasic pattern, with an initial burst release and followed by
      sustained release at a constant rate. After being dissolved in phosphate-buffered
      saline (pH 7.4) and kept at 4 degrees C for one month, the liposomes did not
      aggregate and still had the appearance of a milky white colloidal solution. In a
      pharmacokinetic study, rats treated with RGD-ACM liposomes showed slightly higher
      plasma concentrations than those treated with ACM liposomes. Maximum plasma
      concentrations of RGD-ACM liposomes and ACM liposomes were 4,532 and 3,425 ng/mL,
      respectively. RGD-ACM liposomes had a higher AUC0-infinity (1.54-fold), mean
      residence time (2.09-fold), and elimination half-life (1.2-fold) when compared
      with ACM liposomes. In an in vivo study in mice, both types of liposomes
      inhibited growth of human lung adenocarcinoma (A549) cells and markedly decreased
      tumor size when compared with the control group. There were no obvious
      pathological tissue changes in any of the treatment groups. Our results indicate
      that RGD-modified ACM liposomes have a better antitumor effect in vivo than their
      unmodified counterparts. 

PMID- 26316701
TI  - Pharmacokinetics and bioavailability study of two ondansetron oral soluble film
      formulations in fasting healthy male Chinese volunteers.
AB  - BACKGROUND: Ondansetron oral soluble film is designed to be applied on top of the
      tongue without requiring water to aid dissolution or swallowing, which is
      especially fitting for nausea and vomiting patients. PURPOSE: This study was
      conducted to compare the bioavailability of two 8 mg ondansetron oral soluble
      film formulations. PATIENTS AND METHODS: This randomized, open-label, two-period
      crossover study was performed under fasting conditions. A total of ten eligible
      subjects were randomly assigned at a 1:1 ratio to receive a single 8 mg dose of
      the test and reference ondansetron oral soluble film formulations, followed by a
      1-week washout period and administration of the alternate formulation. The
      concentrations of ondansetron were assayed using an liquid chromatograph-mass
      spectrometer/mass spectrometer (LC-MS/MS) method. For analysis of pharmacokinetic
      properties, including the peak concentration of T max (C max), AUC from time 0
      (baseline) to t hours (AUC0- t ), and AUC from baseline to infinity (AUC0
      infinity), blood samples were obtained at intervals over the 24-hour period after
      studying drug administration. Tolerability was assessed by monitoring vital signs
      and laboratory tests (hematology, blood biochemistry, hepatic function, and
      urinalysis) and by questioning subjects about adverse events. RESULTS: The mean
      (standard derivation [SD]) relative bioavailability was 96.5 (23.7%). The 90%
      confidence intervals (CIs) for the log-transformed ratios of C max and AUC0- t
      were 84.71%-103.28% and 91.38%-108.60%, respectively (P>0.05). Similar results
      were found for the data without log-transformation. No statistically significant
      differences were found based on analysis of variance. No significant adverse
      events occurred or were reported during the study. CONCLUSION: As the 90% CIs
      based on the differences between the test and reference formulation were within
      the 80%-125% range for both the C max and AUC0- t , we concluded that the two
      formulations were bioequivalent with respect to the rate or the extent of
      absorption. Both formulations are well tolerated.

PMID- 26316702
TI  - PTEN insufficiency modulates ER+ breast cancer cell cycle progression and
      increases cell growth in vitro and in vivo.
AB  - Phosphatase and tensin homolog (PTEN), a well-known tumor suppressor gene and
      frequently mutated or lost in breast cancer, possesses the negative regulation
      function over the PI3K/Akt/mTOR pathway. PTEN insufficiency has been associated
      with advanced breast cancer and poor prognosis of breast cancer patients.
      Recently, target therapies aimed at PI3K/Akt/mTOR pathway to treat breast cancer
      have got popularity. However, the exact effect of PTEN on breast cancer cells is
      still not well understood. This study demonstrated that PTEN knockdown in MCF-7
      cells strengthened the downstream gene expressions, including p-Akt, p-ERK1/2, p
      mTOR, p-p70s6k, and p-GSK3beta. PTEN knockdown MCF-7 cells had increased cell
      growth and Ki-67 expression. Further Western blot demonstrated that p27 was
      repressed obviously with p21 slightly inhibited and CDK1, 2, 4, 6, cyclin A, and
      Cdc25C were upregulated in MCF-7 PTEN knockdown cells, leading to the higher
      growth rate. More importantly, PTEN knockdown MCF-7 cells had higher
      tumorigenesis and tumor growth in vivo. From our current work, we provided more
      detailed PTEN-mediated mechanisms to stimulate ER+ breast cancer cell growth. Our
      result may pave the way for further target therapy development used alone or in
      combination with other drugs for ER+ breast cancer with PTEN insufficiency. 

PMID- 26316703
TI  - Myofibrotic malformation vessels: unique angiodysplasia toward the progression of
      hemorrhoidal disease.
AB  - BACKGROUND: The etiology and pathogenesis of hemorrhoids is unclear, although
      hemorrhoids are a worldwide disease in men and women, with peak prevalence at 45
      65 years of age. Hemorrhoidal cushions as the anal venous plexi are normal
      anatomical structures from infancy. This study attempts to reveal the
      angiodysplasia and other pathological changes in association with different
      degrees of symptomatic hemorrhoids. MATERIALS AND METHODS: A total of 281
      patients with internal hemorrhoids from degree I to IV underwent
      hemorrhoidectomy. The vascular changes were analyzed by microscopic assessment
      and software analysis, with Masson's trichrome, CD34, and smooth muscle actin.
      RESULTS: The hemorrhoidal tissues exhibited abnormal vessels in the mucosae and
      submucosae that we termed them as myofibrotic malformation vessels (MMVs). MMVs
      are not ascribed to arteries or veins because they exhibit enlarged and tortuous
      lumens with smooth muscle dysplasia and fibrotic deposition in the walls without
      overlying mucosal ulceration. The muscularis mucosae also showed smooth muscle
      dysplasia and fibrosis, even if it were interrupted by the intruding MMVs. The
      statistical data indicated that the severity of all the changes correlate
      positively with the progression of hemorrhoids (P<0.001). Hemorrhoidal patients
      are prone for reoccurrence even with prolapsing hemorrhoid when compared with the
      conventional hemorrhoidectomy. Multiple logistic regression analysis showed that
      MMVs in mucosal propria, mean thickness of mucosal muscularis layer, and fibrotic
      changes in MMV were independent risk factors for MMVs in hemorrhoidal disease.
      CONCLUSION: MMVs and muscularis mucosae dysplasia reciprocally contribute to
      hemorrhoidal exacerbation. The novel findings of this study propose that the
      characteristic features of MMVs and muscularis mucosae dysplasia of the anorectal
      tube ultimately cause symptomatic hemorrhoids, which could affect the clinical
      management of hemorrhoidal disease through the use of surgery to target the
      malformed vessels.

PMID- 26316704
TI  - Epidural injections with or without steroids in managing chronic low back pain
      secondary to lumbar spinal stenosis: a meta-analysis of 13 randomized controlled
      trials.
AB  - BACKGROUND: Epidural injections of anesthetic with or without steroids are widely
      used for treating lumbar spinal stenosis, a common cause of chronic low back
      pain, but there is a lack of rigorous data comparing the effectiveness of
      epidural injections of anesthetic with and without steroids. This meta-analysis
      presents a current, comprehensive picture of how epidural injections of
      anesthetic with steroids compare with those using local anesthetic alone.
      METHODS: PubMed, Embase, Web of Science, and Cochrane Library databases were
      searched from their inception through February 5, 2015. Weight mean difference,
      risk ratio, and 95% confidence intervals were calculated. A random effects model
      or fixed effects model was used to pool the estimates, according to the
      heterogeneity between the included studies. RESULTS: We included 13 randomized
      controlled trials, involving 1,465 patients. Significant pain relief (>=50%) was
      demonstrated in 53.7% of patients administered with epidural injections of
      anesthetic with steroids (group 1) and in 56.4% of those administered with local
      anesthetic alone (group 2). Patients showed a reduction in numeric rating scale
      pain score of 3.7 and 3.6 in the two groups, respectively. Significant functional
      improvement was achieved in 65.2% of patients in group 1 and 63.1% of patients in
      group 2, with Oswestry Disability Index reductions of 13.8 and 14.5 points,
      respectively. The overall number of injections per year was 3.2+/-1.3 and 3.4+/
      1.2 with average total relief per year of 29.3+/-19.7 and 33.8+/-19.3 weeks,
      respectively. The opioid intakes decreased from baseline by 12.4 and 7.8 mg,
      respectively. Among the outcomes listed, only total relief time differed
      significantly between the two groups. CONCLUSION: Both epidural injections with
      steroids or with local anesthetic alone provide significant pain relief and
      functional improvement in managing chronic low back pain secondary to lumbar
      spinal stenosis, and the inclusion of steroids confers no advantage compared to
      local anesthetic alone.

PMID- 26316705
TI  - Lefty-1 alleviates TGF-beta1-induced fibroblast-myofibroblast
      transdifferentiation in NRK-49F cells.
AB  - Fibroblast activation and proliferation are important for fibroblast
      myofibroblast transdifferentiation, a crucial process in the pathological changes
      that define renal interstitial fibrosis. The left-right determination factor
      (Lefty) is an important cytokine of the transforming growth factor (TGF)-beta
      family, with two variants, Lefty-1 and Lefty-2, in mice. Lefty has diverse
      functions, such as the regulation of embryonic development, the inhibition of TGF
      beta1 signaling, and the suppression of tumor activity. However, whether Lefty-1
      influences fibroblast activation and proliferation, and consequently prevents
      fibroblast-myofibroblast transdifferentiation, remains unclear. This study aimed
      to investigate whether Lefty-1 can attenuate TGF-beta1-induced fibroblast
      myofibroblast transdifferentiation in normal rat kidney interstitial fibroblast
      cells (NRK-49F), as well as the mechanisms underlying any effects. Results showed
      that the typical fibroblast cell morphology of NRK-49F cells was altered after
      TGF-beta1 treatment and that Lefty-1 significantly prevented this change in a
      dose-dependent manner. Further analyses demonstrated decreased proliferating cell
      nuclear antigen, cyclin D1, collagen I(A1), alpha-smooth muscle actin, and
      fibronectin expression. Lefty-1 further induced remarkable reductions in TGF
      beta1-induced Smad3 and mitogen-activated protein kinase-10/c-Jun N-terminal
      kinase (JNK-3) signaling, and enhanced expression of the antifibrotic factor bone
      morphogenetic protein (BMP)-5. However, without TGF-beta1, Lefty-1 had no effect
      on Smad3, JNK-3, and BMP-5 activation and fibroblast-myofibroblast
      transdifferentiation. Taken together, these findings indicate that Lefty-1 can
      alleviate TGF-beta1-mediated activation and the proliferation of fibroblasts.
      Furthermore, Lefty-1 may prevent fibroblast-myofibroblast transdifferentiation in
      part via modulations of Smad3, JNK-3, and BMP-5 activities in the TGF-beta/BMP
      signaling pathway. 

PMID- 26316706
TI  - Treatment with metformin and a dipeptidyl peptidase-4 inhibitor elevates apelin
      levels in patients with type 2 diabetes mellitus.
AB  - BACKGROUND: The objective of this study was to assess the effects of metformin
      monotherapy or combined treatment with a dipeptidyl peptidase-4 inhibitor
      (vildagliptin) on apelin levels in patients with type 2 diabetes mellitus.
      METHODS: Twenty-five patients with poor glycemic control (glycosylated hemoglobin
      >6.5% [48 mmol/mol]) taking 1,000 mg of metformin daily and 25 healthy controls
      matched for age and body mass index were enrolled in this study. Anthropometric
      parameters, glycemic and lipid profile, insulin resistance (homeostasis model
      assessment of insulin resistance index), and apelin levels were measured at
      baseline and at 12-week and 24-week visits. RESULTS: At baseline, apelin levels
      were higher in the T2DM patients than in the controls (1.93+/-1.81 ng/mL versus
      6.09+/-4.90 ng/mL; P<0.05). After 12 weeks, when vildagliptin was added, fasting
      blood glucose and glycosylated hemoglobin decreased, and apelin levels increased
      further (from 6.09+/-4.90 ng/mL to 24.23+/-12.59 ng/mL; P<0.05). Follow-up at 24
      weeks showed no further improvement in the glycemic profile and no further
      increase in apelin levels. CONCLUSION: Both metformin and vildagliptin favorably
      changed glycemic indices and apelin levels. For patients inadequately controlled
      on a low dose of metformin, addition of vildagliptin may be helpful.

PMID- 26316707
TI  - Enhancement of absorption and bioavailability of echinacoside by verapamil or
      clove oil.
AB  - PURPOSE: This present study investigated the absorption kinetics of echinacoside
      (ECH) in situ and in vitro and its oral bioavailability in rats. Additional aim
      was to find an agent(s) to promote ECH absorption and oral bioavailability among
      two efflux proteins and three absorption promoters. METHODS: ECH absorption
      behaviors were investigated by everted gut sac model in vitro and single-pass
      intestinal perfusion model in situ. Pharmacokinetics study was performed to
      investigate the influences of verapamil and clove oil on ECH bioavailability in
      vivo. All samples were measured at different time intervals by high performance
      liquid chromatography. RESULTS: The results showed that the effective
      permeability coefficient (P eff) and apparent permeability coefficient of ECH
      were 0.83*10(-6)-3.23*10(-6) cm/s and 2.99*10(-6)-9.86*10(-6) cm/s, respectively.
      The P eff among duodenum, jejunum, and ileum were not statistically different,
      but they were higher than colon (P<0.01), which demonstrated that intestinal ECH
      absorption was poor and site dependent. Additionally, verapamil and clove oil
      significantly increased the jejunal P eff of ECH both in situ and in vitro.
      Moreover, the bioavailability of ECH in combination with verapamil and clove oil
      were increased by 1.37-fold (P<0.05) and 2.36-fold (P<0.001), respectively, when
      compared to ECH group. Overall, verapamil and clove oil facilitated ECH
      absorption and oral bioavailability. CONCLUSION: The absorption and
      bioavailability of ECH were enhanced by verapamil and clove oil, respectively,
      both in vitro and in vivo. Consequently, the combination of verapamil and clove
      oil with ECH will be a promising and effective approach to promote intestinal
      absorption and oral bioavailability of ECH.

PMID- 26316709
TI  - Development of telmisartan in the therapy of spinal cord injury: pre-clinical
      study in rats.
AB  - BACKGROUND: Decrease of peroxisome proliferator-activated receptors-delta
      (PPARdelta) expression has been observed after spinal cord injury (SCI). Increase
      of PPARdelta may improve the damage in SCI. Telmisartan, the antihypertensive
      agent, has been mentioned to increase the expression of PPARdelta. Thus, we are
      going to screen the effectiveness of telmisartan in SCI for the development of it
      in clinical application. METHODS: In the present study, we used compressive SCI
      in rats. Telmisartan was then used to evaluate the influence in rats after SCI.
      Change in PPARdelta expression was identified by Western blots. Also, behavioral
      tests were performed to check the recovery of damage. RESULTS: Recovery of damage
      from SCI was observed in telmisartan-treated rats. Additionally, this action of
      telmisartan was inhibited by GSK0660 at the dose sufficient to block PPARdelta.
      However, metformin at the dose enough to activate adenosine monophosphate
      activated protein kinase failed to produce similar action as telmisartan. Thus,
      mediation of adenosine monophosphate-activated protein kinase in this action of
      telmisartan can be rule out. Moreover, telmisartan reversed the expressions of
      PPARdelta in rats with SCI. CONCLUSION: The obtained data suggest that
      telmisartan can improve the damage of SCI in rats through an increase in
      PPARdelta expression. Thus, telmisartan is useful to be developed as an agent in
      the therapy of SCI.

PMID- 26316708
TI  - Paget's disease of bone: an osteoimmunological disorder?
AB  - Osteoimmunology represents a large area of research resulting from the cross talk
      between bone and immune systems. Many cytokines and signaling cascades are
      involved in the field of osteoimmunology, originating from various cell types.
      The RANK/receptor activator of nuclear factor Kappa-B ligand
      (RANKL)/osteoprotegerin (OPG) signaling has a pivotal role in osteoimmunology, in
      addition to proinflammatory cytokines such as tumor necrosis factor-alpha,
      interleukin (IL)-1, IL-6, and IL-17. Clinically, osteoimmunological disorders,
      such as rheumatoid arthritis, osteoporosis, and periodontitis, should be
      classified according to their pattern of osteoimmunological serum biomarkers.
      Paget's disease of bone is a common metabolic bone disorder, resulting from an
      excessively increased bone resorption coupled with aberrant bone formation. With
      the exception of the cellular responses to measles virus nucleocapsid protein and
      the interferon-gamma signature, the exact role of the immune system in Paget's
      disease of bone is not well understood. The cytokine profiles, such as the
      increased levels of IL-6 and the interferon-gamma signature observed in this
      disease, are also very similar to those observed in other osteoimmunological
      disorders. As a potential osteoimmunological disorder, the treatment of Paget's
      disease of bone may also benefit from progress made in targeted therapies, in
      particular for receptor activator of nuclear factor Kappa-B ligand and IL-6
      signaling inhibition. 

PMID- 26316711
TI  - Association between glycemic control and antidiabetic drugs in type 2 diabetes
      mellitus patients with cardiovascular complications.
AB  - PURPOSE: Cardiovascular disease (CVD) is a macrovascular complication in patients
      with type 2 diabetes mellitus (T2DM). To date, glycemic control profiles of
      antidiabetic drugs in cardiovascular (CV) complications have not been clearly
      elucidated. Therefore, this study was conducted retrospectively to assess the
      association of antidiabetic drugs and glycemic control with CV profiles in T2DM
      patients. The association of concurrent medications and comorbidities with
      glycemic control was also investigated. METHODS: A total of 220 T2DM patients
      from the University of Malaya Medical Centre, Malaysia, who had at least one CV
      complication and who had been taking at least one antidiabetic drug for at least
      3 months, were included. The associations of antidiabetics, cardiovascular
      diseases, laboratory parameters, concurrent medications, comorbidities,
      demographics, and clinical characteristics with glycemic control were
      investigated. RESULTS: Sulfonylureas in combination (P=0.002) and sulfonylurea
      monotherapy (P<0.001) were found to be associated with good glycemic control,
      whereas insulin in combination (P=0.051), and combination biguanides and insulin
      therapy (P=0.012) were found to be associated with poor glycemic control. Stroke
      (P=0.044) was the only type of CVD that seemed to be significantly associated
      with good glycemic control. Other factors such as benign prostatic hyperplasia
      (P=0.026), elderly patients (P=0.018), low-density lipoprotein cholesterol levels
      (P=0.021), and fasting plasma glucose (P<0.001) were found to be significantly
      correlated with good glycemic control. CONCLUSION: Individualized treatment in
      T2DM patients with CVDs can be supported through a better understanding of the
      association between glycemic control and CV profiles in T2DM patients.

PMID- 26316710
TI  - Death receptor and mitochondria-mediated hepatocyte apoptosis underlies liver
      dysfunction in rats exposed to organic pollutants from drinking water.
AB  - Persistent organic pollutants in drinking water impose a substantial risk to the
      health of human beings, but the evidence for liver toxic effect and the
      underlying mechanism is scarce. This study aimed to examine the liver toxicity
      and elucidate the molecular mechanism of organic pollutants in drinking water in
      normal human liver cell line L02 cells and rats. The data showed that organic
      extraction from drinking water remarkably impaired rat liver function, evident
      from the increase in the serum level of alanine aminotransferase, aspartate
      aminotransferase, and cholinesterase, and decrease in the serum level of total
      protein and albumin. Organic extraction dose-dependently induced apoptotic cell
      death in rat liver and L02 cells. Administration of rats with organic extraction
      promoted death receptor signaling pathway through the increase in gene and
      protein expression level of Fas and FasL. Treatment of rats with organic
      extraction also induced mitochondria-mediated apoptosis via increasing the
      expression level of proapoptotic protein, Bax, but decreasing the expression
      level of antiapoptotic protein, Bcl-2, resulting in an upregulation of cytochrome
      c and activation of caspase cascade at both transcriptional and post
      transcriptional levels. Moreover, organic extraction enhanced rat liver
      glutathione S-transferases activity and reactive oxygen species generation, and
      upregulated aryl hydrocarbon receptor and glutathione S-transferase A1 at both
      transcriptional and translational levels. Collectively, the results indicate that
      organic extraction from drinking water impairs liver function, with the
      involvement of death receptor and mitochondria-mediated apoptosis in rats. The
      results provide evidence and molecular mechanisms for organic pollutants in
      drinking water-induced liver dysfunction, which may help prevent and treat
      organic extraction-induced liver injury. 

PMID- 26316712
TI  - Incidence and risk of hypertension with bevacizumab in non-small-cell lung cancer
      patients: a meta-analysis of randomized controlled trials.
AB  - AIM: A study was conducted to determine the overall risk and incidence of
      hypertension with bevacizumab in non-small-cell lung cancer (NSCLC) patients.
      MATERIALS AND METHODS: Electronic databases such as the Embase, PubMed, and
      Cochrane Library were searched for related trials. Statistical analyses were
      conducted to calculate the overall incidence rates, odds ratios (ORs), and 95%
      confidence intervals (CIs) by using either random-effect or fixed-effect models
      depending on the heterogeneity. RESULTS: A total of 3,155 subjects from nine
      studies were included. The overall incidences of all-grade and high-grade
      hypertension in NSCLC patients were 19.55% (95% CI 10.17%-34.3%) and 6.95% (95%
      CI 5.81%-8.30%). Bevacizumab use was associated with a significantly increased
      risk in all-grade hypertension (OR 8.07, 95% CI 3.87-16.85; P=0.0002) and high
      grade hypertension (OR 5.93, 95% CI 3.41-10.32; P<0.0001). No evidence of
      publication bias was determined for the ORs of hypertension in our meta-analysis.
      CONCLUSION: Bevacizumab is associated with a significantly increased risk of
      hypertension development in NSCLC patients. Early monitoring and effective
      management of hypertension might be important steps for the safe use of this
      drug.

PMID- 26316713
TI  - Effects of chalcone derivatives on players of the immune system.
AB  - The immune system is the defense mechanism in living organisms that protects
      against the invasion of foreign materials, microorganisms, and pathogens. It
      involves multiple organs and tissues in human body, such as lymph nodes, spleen,
      and mucosa-associated lymphoid tissues. However, the execution of immune
      activities depends on a number of specific cell types, such as B cells, T cells,
      macrophages, and granulocytes, which provide various immune responses against
      pathogens. In addition to normal physiological functions, abnormal proliferation,
      migration, and differentiation of these cells (in response to various chemical
      stimuli produced by invading pathogens) have been associated with several
      pathological disorders. The unwanted conditions related to these cells have made
      them prominent targets in the development of new therapeutic interventions
      against various pathological implications, such as atherosclerosis and autoimmune
      diseases. Chalcone derivatives exhibit a broad spectrum of pharmacological
      activities, such as immunomodulation, as well as anti-inflammatory, anticancer,
      antiviral, and antimicrobial properties. Many studies have been conducted to
      determine their inhibitory or stimulatory activities in immune cells, and the
      findings are of significance to provide a new direction for subsequent research.
      This review highlights the effects of chalcone derivatives in different types of
      immune cells. 

PMID- 26316714
TI  - Role of short-acting nitroglycerin in the management of ischemic heart disease.
AB  - Nitroglycerin is the oldest and most commonly prescribed short-acting anti
      anginal agent; however, despite its long history of therapeutic usage, patient
      and health care provider education regarding the clinical benefits of the short
      acting formulations in patients with angina remains under-appreciated. Nitrates
      predominantly induce vasodilation in large capacitance blood vessels, increase
      epicardial coronary arterial diameter and coronary collateral blood flow, and
      impair platelet aggregation. The potential for the prophylactic effect of short
      acting nitrates remains an under-appreciated part of optimal medical therapy to
      reduce angina and decrease myocardial ischemia, thereby enhancing the quality of
      life. Short-acting nitroglycerin, administered either as a sublingual tablet or
      spray, can complement anti-anginal therapy as part of optimal medical therapy in
      patients with refractory and recurrent angina either with or without myocardial
      revascularization, and is most commonly used to provide rapid therapeutic relief
      of acute recurrent angina attacks. When administered prophylactically, both
      formulations increase angina-free walking time on treadmill testing, abolish or
      delay ST segment depression, and increase exercise tolerance. The sublingual
      spray formulation provides several clinical advantages compared to tablet
      formulations, including a lower incidence of headache and superiority to the
      sublingual tablet in terms of therapeutic action and time to onset, while the
      magnitude and duration of vasodilatory action appears to be comparable.
      Furthermore, the sublingual spray formulation may be advantageous to tablet
      preparations in patients with dry mouth. This review discusses the efficacy and
      utility of short-acting nitroglycerin (sublingual spray and tablet) therapy for
      both preventing and aborting an acute angina attack, thereby leading to an
      improved quality of life. 

PMID- 26316716
TI  - How we make cell therapy in Italy.
AB  - In the 21st century scenario, new therapeutic tools are needed to take up the
      social and medical challenge posed by the more and more frequent degenerative
      disorders and by the aging of population. The recent category of advanced therapy
      medicinal products has been created to comprise cellular, gene therapy, and
      tissue engineered products, as a new class of drugs. Their manufacture requires
      the same pharmaceutical framework as for conventional drugs and this means that
      industrial, large-scale manufacturing process has to be adapted to the peculiar
      characteristics of cell-containing products. Our hospital took up the challenge
      of this new path in the early 2000s; and herein we describe the approach we
      followed to set up a pharmaceutical-grade facility in a public hospital context,
      with the aim to share the solutions we found to make cell therapy compliant with
      the requirements for the production and the quality control of a high-standard
      medicinal product. 

PMID- 26316715
TI  - Translational challenges of animal models in Chagas disease drug development: a
      review.
AB  - Chagas disease, or American trypanosomiasis, caused by Trypanosoma cruzi parasite
      infection is endemic in Latin America and presents an increasing clinical
      challenge due to migrating populations. Despite being first identified over a
      century ago, only two drugs are available for its treatment, and recent outcomes
      from the first clinical trials in 40 years were lackluster. There is a critical
      need to develop new drugs to treat Chagas disease. This requires a better
      understanding of the progression of parasite infection, and standardization of
      animal models designed for Chagas disease drug discovery. Such measures would
      improve comparison of generated data and the predictability of test hypotheses
      and models designed for translation to human disease. Existing animal models
      address both disease pathology and treatment efficacy. Available models have
      limited predictive value for the preclinical evaluation of novel therapies and
      need to more confidently predict the efficacy of new drug candidates in clinical
      trials. This review highlights the overall lack of standardized methodology and
      assessment tools, which has hampered the development of efficacious compounds to
      treat Chagas disease. We provide an overview of animal models for Chagas disease,
      and propose steps that could be undertaken to reduce variability and improve
      predictability of drug candidate efficacy. New technological developments and
      tools may contribute to a much needed boost in the drug discovery process. 

PMID- 26316718
TI  - Perampanel in the management of partial-onset seizures: a review of safety,
      efficacy, and patient acceptability.
AB  - Perampanel (PER) is a novel antiepileptic drug recently introduced for the
      adjunctive treatment in epilepsy patients aged 12 years or older with partial
      onset seizures with or without secondary generalization in the US and Europe. Its
      antiepileptic action is based on noncompetitive inhibition of postsynaptic AMPA
      receptors, decreasing excitatory synaptic transmission. Evaluation of efficacy in
      three placebo-controlled randomized Phase III studies showed that add-on therapy
      of PER decreased seizure frequencies significantly compared to placebo at daily
      doses between 4 mg/day and 12 mg/day. PER's long half-life of 105 hours allows
      for once-daily dosing that is favorable for patient compliance with intake. Long
      term extension studies showed a 62.5%-69.6% adherence of patients after 1 year of
      treatment, comparing favorably with other second-generation antiepileptic drugs.
      Whereas these trials demonstrated an overall favorable tolerability profile of
      PER, nonspecific central nervous system adverse effects like somnolence,
      dizziness, headache, and fatigue may occur. In addition, neuropsychiatric
      disturbances ranging from irritability to suicidality were reported in several
      case reports; both placebo-controlled and prospective long-term extension trials
      showed a low incidence of such behavioral and psychiatric complaints. For early
      recognition of neuropsychiatric symptoms like depression, anxiety, and
      aggression, slow titration and close monitoring during drug introduction are
      mandatory. This allows on the one hand to recognize patients particularly
      susceptible to adverse effects of the drug, and on the other hand to render the
      drug's full potential of seizure control available for the vast majority of
      patient groups tolerating the drug well. 

PMID- 26316717
TI  - Nonalcoholic steatohepatitis: emerging targeted therapies to optimize treatment
      options.
AB  - Diet and lifestyle changes have led to worldwide increases in the prevalences of
      obesity and metabolic syndrome, resulting in substantially greater incidence of
      nonalcoholic fatty liver disease (NAFLD). NAFLD is considered a hepatic
      manifestation of metabolic syndrome and is related to diabetes, insulin
      resistance, central obesity, hyperlipidemia, and hypertension. Nonalcoholic
      steatohepatitis (NASH) is an entity that describes liver inflammation due to
      NAFLD. Growing evidence suggests that NAFLD is a multisystem disease with a
      clinical burden that is not only confined to liver-related morbidity and
      mortality, but that also affects several extra-hepatic organs and regulatory
      pathways. Thus, NAFLD is considered an important public health issue, but there
      is currently no effective therapy for all NAFLD patients in the general
      population. Studies seeking optimal therapy for NAFLD and NASH have not yet led
      to development of a universal protocol for treating this growing problem. Several
      pharmacological agents have been studied in an effort to improve insulin
      resistance and the proinflammatory mediators that may be responsible for NASH
      progression. Cardiovascular risk factors are highly prevalent among NASH
      patients, and the backbone of treatment regimens for these patients still
      comprises general lifestyle interventions, including dietary changes and
      increased physical activity. Vitamin E and thiazolidinedione derivatives are
      currently the most evidence-based therapeutic options, but only limited clinical
      evidence is available regarding their long-term efficacy and safety. Vitamin D
      and renin-angiotensin-aldosterone system blockers are promising drugs that are
      currently being intensively investigated for use in NAFLD/NASH patients. 

PMID- 26316719
TI  - Patients' acceptance of corticotomy-assisted orthodontics.
AB  - OBJECTIVE: To study patients' acceptance of corticotomy-assisted orthodontics as
      a treatment option. METHODS: Adult patients seeking orthodontic treatment were
      asked to complete two sets of questionnaires; the first set included questions
      about age, sex, and level of education and general questions about orthodontic
      treatment; and the second set was related to the corticotomy-assisted
      orthodontics. Before answering the corticotomy questions, a brief description of
      the clinical procedure was explained and photographs of an actual procedure were
      shown. RESULTS: A total of 150 subjects were approached and 129 (86%) agreed to
      answer the questionnaires (72 male and 57 female patients). Of these, only 3.1%
      did hear about corticotomy and 7.8% selected corticotomy instead of extraction.
      Fear from the surgery (53.2%) was the most frequent reason for not selecting
      corticotomy followed by fear from pain (36.9%). The acceptance of corticotomy
      between males and females was similar. No relationship was found between the
      level of education and prior knowledge of the procedure, P=0.857. Prior knowledge
      about corticotomy was not a factor in selecting it as a treatment option
      (P=0.556) to reduce the treatment time (P=0.427). CONCLUSION: The acceptance of
      corticotomy-assisted orthodontics as a treatment option was low. Fear from the
      surgery was the main reason for not selecting it. The acceptance of corticotomy
      assisted orthodontics was not related to patient's level of education or sex.

PMID- 26316720
TI  - A comparison of the available phosphodiesterase-5 inhibitors in the treatment of
      erectile dysfunction: a focus on avanafil.
AB  - BACKGROUND: Numerous pathways can lead to erectile dysfunction (ED) in patients,
      with some patients having multiple causes. Regardless of the etiology, ED has
      been successfully treated in many patients with the advent of oral
      phosphodiesterase-5 inhibitors (PDE5Is). With the release of avanafil, there are
      currently four PDE5I options available, and choosing between them should be based
      on patient-specific considerations and preferences. OBJECTIVE: To review the
      treatment of ED with PDE5Is, taking into account the effectiveness, safety, and
      patient satisfaction of these agents, as well as avanafil's place in therapy.
      METHODS: A PubMed search was completed to find articles published in English
      studying patient satisfaction and adherence to ED medication. Additional searches
      looked specifically for any data regarding the use of avanafil. RESULTS: ED is
      effectively treated in most patients with PDE5Is, with the most common side
      effects from the medications being headache, flushing, and visual disturbances.
      Patients have identified many different factors, such as efficacy, side effects,
      duration of action, and daily use, in determining overall satisfaction and the
      right medication for them. While avanafil does not have any patient satisfaction
      trials to date, it has been proven to be a safe and effective treatment for ED
      with possibly the fastest onset of action and fewer visual disturbances than its
      competitors. CONCLUSION: Avanafil along with the other PDE5Is has shown to be a
      safe and effective oral treatment for ED, with avanafil's possible place in
      therapy for patients who want an on-demand option or as an alternative in
      patients who experience visual disturbances with the other agents.

PMID- 26316721
TI  - Detection and correlation analysis of serum cytokines in non-small-cell lung
      cancer patients with bone and non-bone metastases.
AB  - OBJECTIVE: To detect and analyze 13 cytokines that may be related to bone
      metastasis in the serum of non-small-cell lung cancer (NSCLC) patients with bone
      metastases and NSCLC patients with non-bone metastases. PATIENTS AND METHODS: The
      Luminex LiquiChip system was used to detect the concentration of 13 cytokines
      that may be related to bone metastasis in the serum of 30 NSCLC patients with
      bone metastases and 30 with non-bone metastases. RESULTS: The concentration of
      insulin-like growth factor binding protein-3 (IGFBP-3) in the serum of NSCLC
      patients with bone metastases was obviously higher than in non-bone metastasis
      patients (P=0.014). The serum concentration of other cytokines showed no
      significant difference (P>0.05) between the two groups. The concentration of
      IGFBP-3 in the serum of the bone metastasis group was positively correlated to
      VEGF concentration (r=0.804, P=0.009) and monocyte chemotactic protein 1 (MCP-1)
      concentration (r=0.785, P=0.012), but had no correlation to other factors
      (P>0.05). No correlation was found between serum concentrations of cytokines in
      bone metastasis. Concentration of IGFBP-3 in the serum of bone metastasis
      patients was positively correlated to the presence or absence of pain at
      diagnosis (r=0.701, P=0.036) and performance status (PS) score (r=0.670,
      P=0.048), and correlated with the number of bone metastases, sex, age,
      pathological characteristics, T stage, and N stage (P>0.05). CONCLUSION: The
      findings of this study suggest important clinical implications to detect the
      concentration of IGFBP-3 in the serum of lung cancer patients so as to evaluate
      the diagnosis and degree of bone metastasis. Concentration of IGFBP-3 in the
      serum of bone metastasis patients was positively correlated to concentration of
      VEGF and MCP-1, which may be highly relevant for the development of new
      treatments for bone metastasis of lung cancer.

PMID- 26316722
TI  - Risk factors for surgical site infection in a teaching hospital: a prospective
      study of 1,138 patients.
AB  - BACKGROUND: The purpose of this study was to identify risk factors for surgical
      site infection (SSI) in a teaching hospital. METHODS: A prospective study was
      initiated to investigate risk factors for SSI at a university-affiliated tertiary
      care center from July 2013 to December 2014. The chi-square test for categorical
      variables was used to determine the significance of association, whereas the
      multivariate logistic regression model was used to examine independent risk
      factors for SSI. RESULTS: A total of 1,138 patients met the inclusion criteria,
      in whom 36 cases of infection occurred during the hospitalization period and two
      cases occurred after discharge. Univariate analysis showed that SSI was
      associated with the type of operation, wound classification, volume of blood
      loss, blood transfusion, American Society of Anesthesiology score before surgery,
      risk index, duration of surgery, diabetes, cancer, gastrointestinal catheter,
      urinary catheter, postoperative drainage, and preprocedural white blood cell
      count. Multivariate analysis identified six independent parameters correlating
      with the occurrence of SSI: diabetes (odds ratio [OR] 6.400; 95% confidence
      interval [CI] 2.582-15.866; P=0.000); cancer (OR 2.427; 95% CI 1.028-5.732;
      P=0.043); preprocedural white blood cell count more than 10*10(9)/L (OR 6.988; CI
      3.165-15.425; P=0.000); wound classification (clean contaminated [OR: 7.893; CI:
      2.244-27.762; P=0.001]; contaminated [OR: 7.031; CI: 1.652-29.922; P=0.008];
      dirty [OR: 48.778; CI: 5.418-439.164; P=0.001]); operative duration more than 120
      minutes (OR 4.289; CI 1.773-10.378; P=0.001); and postoperative drainage (OR
      3.957; CI 1.422-11.008; P=0.008). CONCLUSION: Our data suggest that all these
      risk factors could be regarded as potential indicators of SSI and that relevant
      preventive measures should be taken to reduce SSI and improve patient outcomes.

PMID- 26316723
TI  - Reduction of exercise capacity in sarcoidosis in relation to disease severity.
AB  - INTRODUCTION: Pulmonary function tests (PFTs) do not always predict functional
      limitations during exercise in sarcoidosis. Cardiopulmonary exercise testing
      (CPET) may facilitate the recognition of exercise intolerance in these patients.
      AIM: As relevant data in sarcoid patients are limited, the aim of the study
      reported here was to assess exercise capacity impairment during a maximal CPET
      and to evaluate potential correlations with PFT measurements and radiological
      stages of the disease. METHOD: A total of 83 sarcoid patients consecutively
      referred for evaluation of exertional dyspnea over a 3-year period were studied
      retrospectively with PFTs, including spirometry, diffusing capacity of the lung
      for carbon monoxide (DLCO) and lung volumes, and CPET using standard protocol.
      Patients were grouped according to their radiological stages: Stage I (n=43),
      Stages II-III (n=31), and Stage IV (n=9). RESULTS: Forced expiratory volume in 1
      second, forced vital capacity, and total lung capacity were mildly impaired only
      in Stage IV (means +/- standard deviation: 72.44+/-28.00, 71.33+/-26.70, and
      59.78+/-21.72, respectively), while DLCO was mildly and moderately reduced in
      Stages II-III and IV (72.68+/-14.13 and 51.22+/-18.50, respectively) and differed
      significantly between all stages (I vs II-III: P=0.003, I vs IV: P=0.003, and II
      III vs IV: P=0.009). Exercise capacity (as expressed by peak oxygen consumption
      <84% predicted) was decreased in 53% of patients (Stage I: 48%, Stages II-III:
      52%, Stage IV: 78%); however, significant differences were noticed only between
      Stages I and IV (P=0.0025). Of note, significant correlations were found between
      peak oxygen consumption and DLCO (P=0.0083), minute ventilation (P<0.0001),
      oxygen pulse (P<0.0001), lactate threshold (P<0.0001), and peak ventilatory
      threshold (P<0.0001). CONCLUSION: CPET could be considered a useful tool in
      exercise intolerance evaluation in sarcoid patients with mild PFT abnormalities.
      Exercise limitation in sarcoidosis may be attributed to both ventilatory and
      cardiocirculatory impairment.

PMID- 26316724
TI  - Analysis of the characteristics and prognosis of advanced non-small-cell lung
      cancer in older patients.
AB  - OBJECTIVE: Lung cancer is still the leading cause of cancer-related deaths
      worldwide. However, most elderly patients with advanced non-small-cell lung
      cancer (NSCLC) have been undertreated and the outcome related to age is
      controversial. A retrospective analysis was conducted for advanced NSCLC in order
      to investigate the characteristics and prognosis of older patients. METHODS:
      Medical records were collected from 165 patients with NSCLC (stages IIIA-IIIB)
      who had been treated with concurrent chemoradiotherapy (CRT) or radiotherapy from
      January 2009 to January 2011. The cases were divided into two age groups 1)
      patients >=70 years old; 2) patients <70 years old. There were 73 patients in
      group I, 92 in group II. Patient characteristics, treatment toxicities, and
      prognosis were evaluated. RESULTS: Of the 165 patients analyzed, 34 patients
      (34/73) in group I received concurrent CRT while 47 (47/92) in group II completed
      that treatment. No significant difference was observed in the reason for patients
      who discontinued CRT in two groups (P>0.05). In the patients with adenocarcinoma,
      more cases were found in group II than that in group I; the more squamous cell
      carcinoma and the more smokers with squamous cell carcinoma were seen in older
      group (P<0.05). With a median follow-up of 20.5 months, the 1-year survival for
      group I and II were 49.3% and 40.2% respectively (P=0.243). Two-year survival for
      the two groups was 20.5% and 16.3% (P=0.483); 3-year survival was 9.6% and 9.8%
      (P=0.967). There was no significant difference between two groups statistically
      in survival by univariate analysis (P>0.05). The therapy-related toxicities in
      group I seem to be similar to the group II (P>0.05). CONCLUSION: More
      adenocarcinoma patients were found in youthful lung cancer and the more smokers
      with squamous cell carcinoma were seen in older group. Age is not the important
      factor for the selection and allocation of treatment in advanced NSCLC. The same
      prognosis and toxicities had been shown in older and young. Age may not be an
      independent increased risk of death in advanced NSCLC.

PMID- 26316725
TI  - Adherence to self-care in patients with heart failure in the HeartCycle study.
AB  - PURPOSE: The purpose of this study was to evaluate a novel online education and
      coaching program to promote self-care among patients with heart failure. In this
      program, education and coaching content is automatically tailored to the
      knowledge and behavior of the patient. PATIENTS AND METHODS: The evaluation of
      the program took place within the scope of the HeartCycle study. This multi
      center, observational study examined the ability of a third generation telehealth
      system to enhance the management of patients recently (<60 days) admitted to the
      hospital for worsening heart failure or outpatients with persistent New York
      Heart Association (NYHA) Functional Classification III/IV symptoms. Self-reported
      self-care behavior was assessed at baseline and study-end by means of the 9-item
      European Heart Failure Self-care Behavior scale. Adherence to daily weighing,
      blood pressure monitoring, and reporting of symptoms was determined by analyzing
      the system's database. RESULTS: Of 123 patients enrolled, the mean age was 66+/
      12 years, 66% were in NYHA III and 79% were men. Self-reported self-care behavior
      scores (n=101) improved during the study for daily weighing, low-salt diet,
      physical activity (P<0.001), and fluid restriction (P<0.05). Average adherence
      (n=120) to measuring weight was 90%+/-16%, to measuring blood pressure was 89%+/
      17% and to symptom reporting was 66%+/-32%. CONCLUSION: Self-reported self-care
      behavior scores improved significantly during the period of observation, and the
      objective evidence of adherence to daily weight and blood pressure measurements
      was high and remained stable over time. However, adherence to daily reporting of
      symptoms was lower and declined in the long-term.

PMID- 26316726
TI  - Safety and feasibility of biventricular devices reuse in general and elderly
      population--a single-center retrospective cohort study.
AB  - INTRODUCTION: Cardiac resynchronization therapy (CRT) is known to have very
      important beneficial effects on heart failure patients. Unfortunately,
      biventricular implantable cardiac devices (CRT devices), through which this
      therapy is implemented, are very expensive and sometimes hard to achieve,
      especially in underdeveloped/developing economies, making this an important
      problem of public health. As a possible solution, CRT reuse is of great interest
      nowadays, but unlike simple devices, data in the literature are scarce about
      biventricular device reuse. AIM: To address safety concerns, we aimed to analyze
      infection burden in the general and elderly population and also early battery
      depletion and generator malfunction of resterilized biventricular devices
      compared to new devices. METHODS: A cohort of 261 CRT patients (286 devices), who
      underwent implantation between 2000 and 2014, was retrospectively analyzed. The
      study group included 115 patients and 127 resterilized devices, that was divided
      into a subgroup of 69 elderly patients (>=60 years) and 74 devices and a subgroup
      of 47 younger patients (<60 years) and 53 devices, and the control group included
      146 patients and 159 new devices. The groups were compared using a multivariate
      logistic regression model. RESULTS: A number of 12 (4.2%) infectious
      complications were encountered, five (3.9%) in the study group and seven (4.4%)
      in the control group (odds ratio, 2.83 [0.59-13.44], P=0.189), one (1.3%) in the
      elderly and four (7.5%) in the younger subgroup (odds ratio, 3.80 [0.36-40.30],
      P=0.266), with no statistically significant difference between them. There was
      only one case of early battery depletion, after 17 months, in one study group
      patient. No generator malfunction was detected. CONCLUSION: Reuse of
      biventricular cardiac implantable electronics seems feasible and safe in both the
      general population and the elderly population, and it could be a promising
      alternative when new devices cannot be obtained in a safe period of time.

PMID- 26316727
TI  - Association between physiological falls risk and physical performance tests among
      community-dwelling older adults.
AB  - BACKGROUND: Physical performance and balance declines with aging and may lead to
      increased risk of falls. Physical performance tests may be useful for initial
      fall-risk screening test among community-dwelling older adults. Physiological
      profile assessment (PPA), a composite falls risk assessment tool is reported to
      have 75% accuracy to screen for physiological falls risk. PPA correlates with
      Timed Up and Go (TUG) test. However, the association between many other commonly
      used physical performance tests and PPA is not known. The aim of the present
      study was to examine the association between physiological falls risk measured
      using PPA and a battery of physical performance tests. METHODS: One hundred and
      forty older adults from a senior citizens club in Kuala Lumpur, Malaysia (94
      females, 46 males), aged 60 years and above (65.77+/-4.61), participated in this
      cross-sectional study. Participants were screened for falls risk using PPA. A
      battery of physical performance tests that include ten-step test (TST), short
      physical performance battery (SPPB), functional reach test (FRT), static balance
      test (SBT), TUG, dominant hand-grip strength (DHGS), and gait speed test (GST)
      were also performed. Spearman's rank correlation and binomial logistic regression
      were performed to examine the significantly associated independent variables
      (physical performance tests) with falls risk (dependent variable). RESULTS:
      Approximately 13% older adults were at high risk of falls categorized using PPA.
      Significant differences (P<0.05) were demonstrated for age, TST, SPPB, FRT, SBT,
      TUG between high and low falls risk group. A significant (P<0.01) weak
      correlation was found between PPA and TST (r=0.25), TUG (r=0.27), SBT (r=0.23),
      SPPB (r=-0.33), and FRT (r=-0.23). Binary logistic regression results
      demonstrated that SBT measuring postural sways objectively using a balance board
      was the only significant predictor of physiological falls risk (P<0.05, odds
      ratio of 2.12). CONCLUSION: The reference values of physical performance tests in
      our study may be used as a guide for initial falls screening to categorize high
      and low physiological falls risk among community-dwelling older adults. A more
      comprehensive assessment of falls risk can be performed thereafter for more
      specific intervention of underlying impairments.

PMID- 26316728
TI  - Comparison of hydration and nutritional status between young and elderly
      hemodialysis patients through bioimpedance analysis.
AB  - BACKGROUND: The number of elderly people on dialysis is increasing rapidly. Fluid
      overload and malnutrition status are serious problems in elderly dialysis
      patients. We aimed to compare the hydration and nutritional status through
      bioimpedance analysis (BIA) between young and elderly hemodialysis (HD) patients
      and to analyze risk factors related to fluid overload and malnutrition status in
      these patients. METHOD: We conducted a cross-sectional study, in which 82 HD
      (males 42, mean age 58.7+/-12.9 years) patients were enrolled. We collected
      different types of data: laboratory data, such as serum creatinine, albumin,
      total iron-binding capacity, hemoglobin, total cholesterol; anthropometric data,
      such as hand grip strength (HGS); BIA data, such as intracellular water, skeletal
      muscle mass, body cell mass, bone mineral content, phase angle (PhA), extra
      cellular water (ECW)/total body water (TBW) ratio; and malnutrition-inflammation
      score (MIS), which is a traditional nutritional parameter for dialysis patients.
      All patients were stratified into two groups according to their age: young (<65
      years [n=54]) and elderly (>=65 years [n=28]). RESULTS: Total iron-binding
      capacity and HGS were significantly lower in elderly HD patients than in young HD
      patients (198.9+/-35.6 vs 221.4+/-52.1 mcg/dL; and 22.4+/-10.3 vs 36.4+/-23.2 kg,
      respectively) (P<0.05). Also, intracellular water and PhA measured by BIA were
      significantly lower (18.3+/-4.0 vs 20.3+/-4.2 L [P=0.043]; and 4.0+/-1.0 vs 4.9+/
      1.2 degrees  [P=0.002], respectively), and ECW/TBW were higher in elderly HD
      patients (0.40+/-0.01 vs 0.39+/-0.01 [P=0.001]). ECW/TBW was positively
      associated with age (P<0.001) and the presence of diabetes (P<0.001) and was
      negatively associated with sex (P=0.001), albumin (P<0.001), urine volume
      (P=0.042), HGS (P<0.001), and PhA by BIA (P<0.001). MIS was negatively related to
      sex (P=0.001), albumin (P<0.001), HGS (P=0.001), and PhA (P<0.001) in HD
      patients. On multivariate analysis, older age (P=0.031), the presence of diabetes
      (P=0.035), and decreased PhA (P<0.001) were independent risk factors for
      increased ECW/TBW, representative of fluid overload status, whereas only
      decreased PhA (P=0.008) was a significant factor for MIS, representative of
      malnutrition status in these HD patients. CONCLUSION: We found that fluid
      overload and malnutrition status were more common in elderly HD patients compared
      with young HD patients. PhA was a significant independent factor in fluid
      overload status and malnutrition in these HD patients. Thus, our results
      indicated that PhA assessed by BIA might be a clinically useful method for
      assessing nutritional and hydration status in elderly HD patients.

PMID- 26316729
TI  - Does multicomponent physical exercise with simultaneous cognitive training boost
      cognitive performance in older adults? A 6-month randomized controlled trial with
      a 1-year follow-up.
AB  - BACKGROUND: Cognitive impairment is a health problem that concerns almost every
      second elderly person. Physical and cognitive training have differential positive
      effects on cognition, but have been rarely applied in combination. This study
      evaluates synergistic effects of multicomponent physical exercise complemented
      with novel simultaneous cognitive training on cognition in older adults. We
      hypothesized that simultaneous cognitive-physical components would add training
      specific cognitive benefits compared to exclusively physical training. METHODS:
      Seniors, older than 70 years, without cognitive impairment, were randomly
      assigned to either: 1) virtual reality video game dancing (DANCE), 2) treadmill
      walking with simultaneous verbal memory training (MEMORY), or 3) treadmill
      walking (PHYS). Each program was complemented with strength and balance
      exercises. Two 1-hour training sessions per week over 6 months were applied.
      Cognitive performance was assessed at baseline, after 3 and 6 months, and at 1
      year follow-up. Multiple regression analyses with planned comparisons were
      calculated. RESULTS: Eighty-nine participants were randomized to the three groups
      initially, 71 completed the training, while 47 were available at 1-year follow
      up. Advantages of the simultaneous cognitive-physical programs were found in two
      dimensions of executive function. "Shifting attention" showed a time*intervention
      interaction in favor of DANCE/MEMORY versus PHYS (F[2, 68] =1.95, trend P=0.075,
      r=0.17); and "working memory" showed a time*intervention interaction in favor of
      DANCE versus MEMORY (F[1, 136] =2.71, trend P=0.051, R (2)=0.006). Performance
      improvements in executive functions, long-term visual memory (episodic memory),
      and processing speed were maintained at follow-up in all groups. CONCLUSION:
      Particular executive functions benefit from simultaneous cognitive-physical
      training compared to exclusively physical multicomponent training. Cognitive
      physical training programs may counteract widespread cognitive impairments in the
      elderly.

PMID- 26316730
TI  - Beneficial effects of multisensory and cognitive stimulation in institutionalized
      elderly: 12-months follow-up.
AB  - We previously demonstrated the beneficial effects of a multisensory and cognitive
      stimulation program, consisting of 48 sessions, twice a week, to improve the
      cognition of elderly subjects living either in long-term care institutions
      (institutionalized - I) or in communities with their families
      (noninstitutionalized - NI). In the present study, we evaluated these subjects
      after the end of the intervention and compared the rate of age-related cognitive
      decline of those living in an enriched community environment (NI group, n=15,
      74.1+/-3.9 years old) with those living in the impoverished environment of long
      term care institutions (I group, n=20, 75.1+/-6.8 years old). Both groups
      participated fully in our stimulation program. Over 1 year, we conducted
      revaluations at five time points (2 months, 4 months, 6 months, 8 months, and 12
      months) after the completion of the intervention. Both elderly groups were
      evaluated with the mini-mental state examination and selected language tests.
      Progressive cognitive decline was observed in both groups over the period.
      Indeed, it took only 4-6 months after the end of the stimulation program for
      significant reductions in language test scores to become apparent. However,
      earlier reductions in test scores were mainly associated with I group, and
      linguistic prosody test scores were significantly affected by
      institutionalization and time, two variables that interacted and reduced these
      scores. Moreover, I group reduced the Montreal cognitive assessment battery
      language tests scores 4 months before NI group. It remains to be investigated
      what mechanisms may explain the earlier and more intense language losses in
      institutionalized elderly. 

PMID- 26316731
TI  - Sex differences of continuous positive airway pressure treatment on flow-mediated
      dilation in patients with obstructive sleep apnea syndrome.
AB  - INTRODUCTION: There is growing research evidence suggesting the presence of
      endothelial dysfunction and systemic inflammation in patients with obstructive
      sleep apnea syndrome (OSAS). Continuous positive airway pressure (CPAP) is the
      most effective method for treating OSAS; nonetheless, the effects of CPAP on the
      aforementioned pathophysiologic pathways as well as on the systemic disease that
      result or coexist with the OSAS remain elusive. AIM: To assess the effect of 3
      month CPAP therapy on endothelial-dependent dilation, plasma levels of
      inflammatory markers, blood pressure (BP), and glucose control on male and female
      patients with OSAS. METHODS: Our study group consisted of 40 (24 males and 16
      females) patients with no prior history of cardiovascular disease, with an apnea
      hypopnea index >=15, who were assigned to receive CPAP treatment. Measurements of
      flow-mediated dilation (FMD), 24-hour ambulatory BP, and blood analysis were
      performed at baseline and 3 months after CPAP therapy. RESULTS: Baseline FMD
      values were negatively correlated with the apnea-hypopnea index (r=-0.55,
      P=0.001). After 3 months of CPAP, there was an increase in the FMD values
      (5.40%+/-2.91% vs 3.13%+/-3.15%, P<0.05) and a significant reduction in the
      patients' 24-hour systolic BP (122.82+/-11.88 mmHg vs 130.24+/-16.75 mmHg,
      P<0.05), diastolic BP (75.44+/-9.14 mmHg vs 79.68+/-11.09 mmHg, P<0.05), and
      pulse pressure (47.38+/-9.77 mmHg vs 52.72+/-11.38 mmHg, P<0.05); daytime
      systolic BP (125.76+/-12.69 mmHg vs 132.55+/-17.00 mmHg, P<0.05) and diastolic BP
      (77.88+/-10.39 mmHg vs 82.25+/-11.01 mmHg, P<0.05); nighttime systolic BP
      (118.17+/-13.16 mmHg vs 126.22+/-17.42 mmHg, P<0.05) and pulse pressure (46.61+/
      10.76 mmHg vs 52.66+/-11.86 mmHg, P<0.05); and C-reactive protein and HbA1c
      levels (0.40 [0.40-0.70] mg/L vs 0.60 [0.40-0.84] mg/L and 5.45%+/-0.70% vs
      5.95%+/-1.08%, respectively; P<0.05). When divided by sex, only male patients
      produced similar statistically significant results, while female patients failed
      to show such associations. CONCLUSION: Our results suggest that CPAP therapy
      improves the endothelial function, the BP, and the glucose control in male
      patients with OSAS. Further research is warranted in order to verify these
      results and to further elucidate the impact of CPAP on the cardiovascular risk of
      male and female patients with OSAS.

PMID- 26316732
TI  - Association of brachial-ankle pulse wave velocity with atherosclerosis and
      presence of coronary artery disease in older patients.
AB  - OBJECTIVE: Brachial-ankle pulse wave velocity (baPWV) is a simple and
      reproducible measure of arterial stiffness and is extensively used to assess risk
      of cardiovascular disease in Asia. We examined whether baPWV was associated with
      coronary atherosclerosis and presence and extent of coronary artery disease (CAD)
      in older patients with chest pain. METHODS: This cross-sectional study enrolled
      370 consecutive patients >65 years old who underwent baPWV measurement and
      elective coronary angiogram for suspected CAD at a single cardiovascular center,
      between June 2013 and July 2014. RESULTS: In addition to diabetes mellitus and
      body mass index, baPWV was one of the statistically meaningful predictors of
      significant CAD (diameter of stenosis >50%) in a multivariate analysis. When the
      extent of CAD was classified as nonsignificant or significant CAD (ie, one-, two
      , and three-vessel disease), there was a significant difference in baPWV between
      the significant and nonsignificant CAD groups, but not between the three
      significant CAD groups. Multivariate linear regression analyses showed that the
      number of diseased vessels and baPWV were both significantly associated with the
      SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac
      surgery) score. The cutoff value of baPWV at 1,874 cm/s had a sensitivity of
      60.1%, specificity of 70.8%, and area under receiver operating characteristic
      curve of 0.639 in predicting CAD. CONCLUSION: Arterial stiffness determined by
      baPWV was associated independently with CAD severity, as assessed by angiography
      and the SYNTAX score in older patients with chest pain. As a result, increased
      arterial stiffness assessed by baPWV is associated with the severity and presence
      of CAD in older patients.

PMID- 26316733
TI  - Hormonal determinants of the severity of andropausal and depressive symptoms in
      middle-aged and elderly men with prediabetes.
AB  - Andropausal and depressive symptoms are common in aging males and may be
      associated with hormone deficiency. We investigated the severity of andropausal
      and depressive symptoms, as well as their hormonal determinants, in 196 middle
      aged and elderly men (age range: 40-80 years) with prediabetes (PD) and in 184
      healthy peers. PD was diagnosed according to the definition of the American
      Diabetes Association. The severity of andropausal and depressive symptoms was
      assessed using the Aging Males' Symptoms Rating Scale and the Self-Rating
      Depression Scale. Total testosterone (TT), calculated free testosterone (cFT),
      dehydroepiandrosterone sulfate (DHEAS), and insulin-like growth factor 1 (IGF-1)
      were measured. The prevalence of andropausal syndrome in men with PD was
      significantly higher than that in healthy men (35% vs 11%, respectively). In men
      with PD aged 40-59 years, the severity of sexual, psychological, and all
      andropausal symptoms was greater than in healthy peers, while in elderly men (60
      80 years), only the severity of psychological symptoms was greater than in
      healthy peers. The severity of depressive symptoms in the middle-aged men with PD
      was greater than in healthy peers, while the severity of depressive symptoms in
      elderly men with PD and healthy peers was similar. The higher prevalence of
      andropausal symptoms was independently associated with cFT and IGF-1 in middle
      aged men and with TT and DHEAS in elderly men with PD. The more severe depression
      symptoms were associated with low TT and DHEAS in middle-aged men and with low
      cFT and DHEAS in elderly men with PD. In conclusion, the prevalence of
      andropausal symptoms, especially psychological, was higher in prediabetic
      patients as compared to healthy men, while the severity of depressive symptoms
      was higher only in middle-aged men with PD. Hormonal determinants of andropausal
      and depressive symptoms are different in middle-aged and elderly patients, but
      endocrine tests are necessary in all men with PD. 

PMID- 26316734
TI  - Safety of inhaled glycopyrronium in patients with COPD: a comprehensive analysis
      of clinical studies and post-marketing data.
AB  - BACKGROUND: Chronic use of inhaled anticholinergics by patients with chronic
      obstructive pulmonary disease (COPD) has raised long-term safety concerns,
      particularly cardiovascular. Glycopyrronium is a once-daily anticholinergic with
      greater receptor selectivity than previously available agents. METHODS: We
      assessed the safety of inhaled glycopyrronium using data pooled from two analysis
      sets, involving six clinical studies and over 4,000 patients with COPD who
      received one of the following treatments: glycopyrronium 50 MUg, placebo (both
      delivered via the Breezhaler device), or tiotropium 18 MUg (delivered via the
      HandiHaler device). Data were pooled from studies that varied in their duration
      and severity of COPD of the patients (ie, <=12 weeks duration with patients
      having moderate or severe COPD; and >1 year duration with patients having severe
      and very severe COPD). Safety comparisons were made for glycopyrronium vs
      tiotropium or placebo. Poisson regression was used to assess the relative risk
      for either active drug or placebo (and between drugs where placebo was not
      available) for assessing the incidence of safety events. During post-marketing
      surveillance (PMS), safety was assessed by obtaining reports from various
      sources, and disproportionality scores were computed using EMPIRICA. In
      particular, the cardiac safety of glycopyrronium during the post-marketing phase
      was evaluated. RESULTS: The overall incidence of adverse events and deaths was
      similar across groups, while the incidence of serious adverse events was
      numerically higher in placebo. Furthermore, glycopyrronium did not result in an
      increased risk of cerebro-cardiovascular events vs placebo. There were no new
      safety reports during the PMS phase that suggested an increased risk compared to
      results from the clinical studies. Moreover, the cardiac safety of glycopyrronium
      during the PMS phase was also consistent with the clinical data. CONCLUSION: The
      overall safety profile of glycopyrronium was similar to its comparators
      indicating no increase in the overall risk for any of the investigated safety end
      points.

PMID- 26316735
TI  - VitalQPlus: a potential screening tool for early diagnosis of COPD.
AB  - BACKGROUND: This study utilized a validated combination of a COPD Population
      Screener (COPD-PS) questionnaire and a handheld spirometric device as a screening
      tool for patients at high risk of COPD, such as smokers. The study aimed to
      investigate and pilot the feasibility and application of this combined
      assessment, which we termed the "VitalQPlus", as a screening tool for the early
      detection of COPD, especially in primary care settings. METHODS: This was a cross
      sectional study screening potentially undiagnosed COPD patients using a validated
      five-item COPD-PS questionnaire together with a handheld spirometric device.
      Patients were recruited from selected Malaysian government primary care health
      centers. RESULTS: Of the total of 83 final participants, only 24.1% (20/83) were
      recruited from Perak and Penang (peninsular Malaysia) compared to 75.9% (63/83)
      from Sabah (Borneo region). Our dual assessment approach identified 8.4% of the
      surveyed patients as having potentially undiagnosed COPD. When only the
      Vitalograph COPD-6 screening tool was used, 15.8% of patients were detected with
      a forced expiratory volume in 1 second/forced expiratory volume in 6 seconds
      (FEV1/FEV6) ratio at <0.75, while 35.9% of patients were detected with the COPD
      PS questionnaire. These findings suggested that this dual assessment approach has
      a greater chance of identifying potentially undiagnosed COPD patients compared to
      the Vitalograph COPD-6 or COPD-PS questionnaire when used alone. Our findings
      show that patients with more symptoms (scores of >=5) yielded twice the
      percentage of outcomes of FEV1/FEV6 <0.75 compared to patients with fewer COPD
      symptoms (scores <5). CONCLUSION: With the availability of a simple screening
      questionnaire and the COPD-6, there is an opportunity easily to make patients
      more aware of their lung symptoms and to encourage the provision of early
      treatment. The proposed dual assessment approach, which we termed the VitalQPlus,
      may play a profound role in the early diagnosis of COPD, which is crucial in
      improving the clinical management of the disease.

PMID- 26316736
TI  - Discrepancies between modified Medical Research Council dyspnea score and COPD
      assessment test score in patients with COPD.
AB  - BACKGROUND AND OBJECTIVE: According to the Global Initiative for Chronic
      Obstructive Lung Disease (GOLD) guidelines, either a modified Medical Research
      Council (mMRC) dyspnea score of >=2 or a chronic obstructive pulmonary disease
      (COPD) assessment test (CAT) score of >=10 is considered to represent COPD
      patients who are more symptomatic. We aimed to identify the ideal CAT score that
      exhibits minimal discrepancy with the mMRC score. METHODS: A receiver operating
      characteristic curve of the CAT score was generated for an mMRC scores of 1 and
      2. A concordance analysis was applied to quantify the association between the
      frequencies of patients categorized into GOLD groups A-D using symptom cutoff
      points. A kappa-coefficient was calculated. RESULTS: For an mMRC score of 2, a
      CAT score of 15 showed the maximum value of Youden's index with a sensitivity and
      specificity of 0.70 and 0.66, respectively (area under the receiver operating
      characteristic curve [AUC] 0.74; 95% confidence interval [CI], 0.70-0.77). For an
      mMRC score of 1, a CAT score of 10 showed the maximum value of Youden's index
      with a sensitivity and specificity of 0.77 and 0.65, respectively (AUC 0.77; 95%
      CI, 0.72-0.83). The kappa value for concordance was highest between an mMRC score
      of 1 and a CAT score of 10 (0.66), followed by an mMRC score of 2 and a CAT score
      of 15 (0.56), an mMRC score of 2 and a CAT score of 10 (0.47), and an mMRC score
      of 1 and a CAT score of 15 (0.43). CONCLUSION: A CAT score of 10 was most
      concordant with an mMRC score of 1 when classifying patients with COPD into GOLD
      groups A-D. However, a discrepancy remains between the CAT and mMRC scoring
      systems.

PMID- 26316737
TI  - Differences in the use of spirometry between rural and urban primary care centers
      in Spain.
AB  - OBJECTIVES: The aim of this study is to evaluate the ability and practice of
      spirometry, training of technicians, and spirometry features in primary care
      centers in Spain, evaluating those located in a rural environment against those
      in urban areas. METHODS: An observational cross-sectional study was conducted in
      2012 by a telephone survey in 970 primary health care centers in Spain. The
      centers were divided into rural or urban depending on the catchment population.
      The survey contacted technicians in charge of spirometry and consisted of 36
      questions related to the test that included the following topics: center
      resources, training doctors and technicians, using the spirometer, bronchodilator
      test, and the availability of spirometry and maintenance. RESULTS: Although the
      sample size was achieved in both settings, rural centers (RCs) gave a lower
      response rate than urban centers (UCs). The number of centers without spirometry
      in rural areas doubled those in the urban areas. Most centers had between one and
      two spirometers. However, the number of spirometry tests per week was
      significantly lower in RCs than in UCs (4 [4.1%] vs 6.9 [5.7%], P<0.01). The
      availability of a specific schedule for conducting spirometries was higher in RCs
      than in UCs (209 [73.0%] vs 207 [64.2%], P=0.003). RCs were more satisfied with
      the spirometries (7.8 vs 7.6, P=0.019) and received more training course for
      interpreting spirometry (41.0% vs 33.2%, P=0.004). The performance of the
      bronchodilator test showed a homogeneous measure in different ways. The
      spirometer type and the reference values were unknown to the majority of
      respondents. CONCLUSION: This study shows the differences between primary care
      RCs and UCs in Spain in terms of performing spirometry. The findings in the
      present study can be used to improve the performance of spirometry in these
      areas.

PMID- 26316738
TI  - A variant in 3'-untranslated region of KRAS compromises its interaction with hsa
      let-7g and contributes to the development of lung cancer in patients with COPD.
AB  - OBJECTIVE: The objective of the present study was to explore the molecular
      mechanism by which a single nucleotide polymorphism (rs712) interferes with
      interaction between 3'-untranslated region (3'-UTR) of KRAS and let-7g, and its
      association with development of lung cancer in the patients with COPD. MATERIALS
      AND METHODS: In this study, we confirmed that KRAS is a target of let-7g in lung
      cancer cells, and that introduction of rs712 minor allele into 3'-UTR
      significantly compromised the miRNA/mRNA interaction by using a luciferase
      reporter system. Additionally, a total of 35 lung tissue samples were obtained
      (TT:17, TG:12, GG:6), and let-7g and KRAS expression levels were determined.
      RESULTS: We showed that let-7g level was similar between groups, and the
      concentration of KRAS in GG genotype group was significantly higher than in TT or
      GT genotype group. Meanwhile, we found COPD patients with GG genotype had
      significantly higher risk for lung cancer (odds ratio OR =6.83, P=0.0081),
      compared with TT and GT genotypes. CONCLUSION: Our study demonstrated that KRAS
      3'-UTR rs712 polymorphism interfered with miRNA/mRNA interaction, and showed that
      the minor allele was associated with an elevated risk for development of lung
      cancer in COPD.

PMID- 26316739
TI  - Relationship between linear and nonlinear dynamics of heart rate and impairment
      of lung function in COPD patients.
AB  - BACKGROUND: In chronic obstructive pulmonary disease (COPD), functional and
      structural impairment of lung function can negatively impact heart rate
      variability (HRV); however, it is unknown if static lung volumes and lung
      diffusion capacity negatively impacts HRV responses. We investigated whether
      impairment of static lung volumes and lung diffusion capacity could be related to
      HRV indices in patients with moderate to severe COPD. METHODS: Sixteen sedentary
      males with COPD were enrolled in this study. Resting blood gases, static lung
      volumes, and lung diffusion capacity for carbon monoxide (DLCO) were measured.
      The RR interval (RRi) was registered in the supine, standing, and seated
      positions (10 minutes each) and during 4 minutes of a respiratory sinus
      arrhythmia maneuver (M-RSA). Delta changes (Deltasupine-standing and Deltasupine
      M-RSA) of the standard deviation of normal RRi, low frequency (LF, normalized
      units [nu]) and high frequency (HF [nu]), SD1, SD2, alpha1, alpha2, and
      approximate entropy (ApEn) indices were calculated. RESULTS: HF, LF, SD1, SD2,
      and alpha1 deltas significantly correlated with forced expiratory volume in 1
      second, DLCO, airway resistance, residual volume, inspiratory capacity/total lung
      capacity ratio, and residual volume/total lung capacity ratio. Significant and
      moderate associations were also observed between LF/HF ratio versus total gas
      volume (%), r=0.53; LF/HF ratio versus residual volume, %, r=0.52; and HF versus
      total gas volume (%), r=-0.53 (P<0.05). Linear regression analysis revealed that
      DeltaRRi supine-M-RSA was independently related to DLCO (r=-0.77, r (2)=0.43,
      P<0.05). CONCLUSION: Responses of HRV indices were more prominent during M-RSA in
      moderate to severe COPD. Moreover, greater lung function impairment was related
      to poorer heart rate dynamics. Finally, impaired lung diffusion capacity was
      related to an altered parasympathetic response in these patients.

PMID- 26316740
TI  - Modified Medical Research Council scale vs Baseline Dyspnea Index to evaluate
      dyspnea in chronic obstructive pulmonary disease.
AB  - BACKGROUND: Assessment of dyspnea in COPD patients relies in clinical practice on
      the modified Medical Research Council (mMRC) scale, whereas the Baseline Dyspnea
      Index (BDI) is mainly used in clinical trials. Little is known on the
      correspondence between the two methods. METHODS: Cross-sectional analysis was
      carried out on data from the French COPD cohort Initiatives BPCO. Dyspnea was
      assessed by the mMRC scale and the BDI. Spirometry, plethysmography, Hospital
      Anxiety-Depression Scale, St George's Respiratory Questionnaire, exacerbation
      rates, and physician-diagnosed comorbidities were obtained. Correlations between
      mMRC and BDI scores were assessed using Spearman's correlation coefficient. An
      ordinal response model was used to examine the contribution of clinical data and
      lung function parameters to mMRC and BDI scores. RESULTS: Data are given as
      median (interquartile ranges, [IQR]). Two-hundred thirty-nine COPD subjects were
      analyzed (men 78%, age 65.0 years [57.0; 73.0], forced expiratory volume in 1
      second [FEV1] 48% predicted [34; 67]). The mMRC grade and BDI score were,
      respectively, 1 [1-3] and 6 [4-8]. Both BDI and mMRC scores were significantly
      correlated at the group level (rho =-0.67; P<0.0001), but analysis of individual
      data revealed a large scatter of BDI scores for any given mMRC grade. In
      multivariate analysis, both mMRC grade and BDI score were independently
      associated with lower FEV1% pred, higher exacerbation rate, obesity, depression,
      heart failure, and hyperinflation, as assessed by the inspiratory capacity/total
      lung capacity ratio. The mMRC dyspnea grade was also associated with the
      thromboembolic history and low body mass index. CONCLUSION: Dyspnea is a complex
      symptom with multiple determinants in COPD patients. Although related to similar
      factors (including hyperinflation, depression, and heart failure), BDI and mMRC
      scores likely explore differently the dyspnea intensity in COPD patients and are
      clearly not interchangeable.

PMID- 26316741
TI  - Efficacy and safety of the long-acting beta2-agonist olodaterol over 4 weeks in
      Japanese patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: Olodaterol is a novel long-acting beta2-agonist with proven >=24-hour
      duration of action in preclinical and clinical studies. OBJECTIVE: This
      randomized, double-blind, placebo-controlled, parallel-group study evaluated the
      dose response of once-daily (QD) olodaterol based on bronchodilator efficacy,
      safety, and pharmacokinetics over 4 weeks in Japanese patients with chronic
      obstructive pulmonary disease (COPD). METHODS: All eligible patients were
      randomized to receive 2 ug, 5 ug, or 10 ug of olodaterol or placebo for 4 weeks
      via the Respimat Soft Mist inhaler. The primary end point was the change from
      baseline in trough forced expiratory volume in 1 second (FEV1) after 4 weeks of
      olodaterol treatment. Secondary end points included trough FEV1 after 1 week and
      2 weeks of treatment, FEV1 area under the curve from 0 hour to 3 hours (AUC(0
      3)), peak FEV1 from 0 hour to 3 hours (peak FEV1), and corresponding forced vital
      capacity (FVC) responses. Rescue medication use, COPD symptoms, physician global
      evaluation, pharmacokinetics, and safety were also assessed. RESULTS: A total of
      328 patients with COPD were randomized to receive treatment. All olodaterol doses
      assessed in the study showed statistically significant increases in trough FEV1
      compared to placebo at Day 29 (P<0.0001). Mean increases in peak FEV1 and FEV1
      AUC(0-3) compared to placebo were also significant (P<0.0001). A clear dose
      response relationship was observed across all treatment groups. FVC responses
      (trough and FVC AUC(0-3)) supported FEV1 outcomes. All doses of olodaterol were
      well tolerated, and no safety concerns were identified. CONCLUSION: QD olodaterol
      demonstrated 24-hour bronchodilator efficacy and was well tolerated in Japanese
      patients with COPD. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00824382.

PMID- 26316742
TI  - Enhancement of radiotherapy by ceria nanoparticles modified with neogambogic acid
      in breast cancer cells.
AB  - Radiotherapy is one of the main strategies for cancer treatment but has
      significant challenges, such as cancer cell resistance and radiation damage to
      normal tissue. Radiosensitizers that selectively increase the susceptibility of
      cancer cells to radiation can enhance the effectiveness of radiotherapy. We
      report here the development of a novel radiosensitizer consisting of
      monodispersed ceria nanoparticles (CNPs) covered with the anticancer drug
      neogambogic acid (NGA-CNPs). These were used in conjunction with radiation in MCF
      7 breast cancer cells, and the efficacy and mechanisms of action of this combined
      treatment approach were evaluated. NGA-CNPs potentiated the toxic effects of
      radiation, leading to a higher rate of cell death than either treatment used
      alone and inducing the activation of autophagy and cell cycle arrest at the G2/M
      phase, while pretreatment with NGA or CNPs did not improve the rate of radiation
      induced cancer cells death. However, NGA-CNPs decreased both endogenous and
      radiation-induced reactive oxygen species formation, unlike other nanomaterials.
      These results suggest that the adjunctive use of NGA-CNPs can increase the
      effectiveness of radiotherapy in breast cancer treatment by lowering the
      radiation doses required to kill cancer cells and thereby minimizing collateral
      damage to healthy adjacent tissue. 

PMID- 26316744
TI  - Adherence ability of Staphylococcus epidermidis on prosthetic biomaterials: an in
      vitro study [Corrigendum].

PMID- 26316743
TI  - Pharmacological characterization of nanoparticle-induced platelet
      microaggregation using quartz crystal microbalance with dissipation: comparison
      with light aggregometry.
AB  - BACKGROUND: Engineered nanoparticles (NPs) can induce platelet activation and
      aggregation, but the mechanisms underlying these interactions are not well
      understood. This could be due in part to use of devices that study platelet
      function under quasi-static conditions with low sensitivity to measure platelet
      microaggregation. Therefore, in this study we investigated the pharmacological
      pathways and regulators of NP-induced platelet microaggregation under flow
      conditions at nanoscale using quartz crystal microbalance with dissipation (QCM
      D) and compared the data thus obtained with those generated by light
      aggregometry. METHODS: Blood was collected from healthy volunteers, and platelet
      rich plasma was obtained. Thrombin receptor-activating peptide, a potent
      stimulator of platelet function, and pharmacological inhibitors were used to
      modulate platelet microaggregation in the presence/absence of silica (10 nm and
      50 nm) and polystyrene (23 nm) NPs. Light aggregometry was used to study platelet
      aggregation in macroscale. Optical, immunofluorescence, and scanning electron
      microscopy were also used to visualize platelet aggregates. RESULTS: Platelet
      microaggregation was enhanced by thrombin receptor-activating peptide, whereas
      prostacyclin, nitric oxide donors, acetylsalicylic acid, and phenanthroline, but
      not adenosine diphosphate (ADP) blockers, were able to inhibit platelet
      microaggregation. NPs caused platelet microaggregation, an effect not detectable
      by light aggregometry. NP-induced microaggregation was attenuated by platelet
      inhibitors. CONCLUSION: NP-induced platelet microaggregation appears to involve
      classical proaggregatory pathways (thromboxane A2-mediated and matrix
      metalloproteinase-2-mediated) and can be regulated by endogenous (prostacyclin)
      and pharmacological (acetylsalicylic acid, phenanthroline, and nitric oxide
      donors) inhibitors of platelet function. Quartz crystal microbalance with
      dissipation, but not light aggregometry, is an appropriate method for studying NP
      induced microaggregation.

PMID- 26316745
TI  - Lactoferrin-modified PEGylated liposomes loaded with doxorubicin for targeting
      delivery to hepatocellular carcinoma.
AB  - Lactoferrin (Lf) is a potential-targeting ligand for hepatocellular carcinoma
      (HCC) cells because of its specific binding with asialoglycoprotein receptor
      (ASGPR). In this present work, a doxorubicin (DOX)-loaded, Lf-modified,
      polyethylene glycol (PEG)ylated liposome (Lf-PLS) system was developed, and its
      targeting effect and antitumor efficacy to HCC was also explored. The DOX-loaded
      Lf-PLS system had spherical or oval vesicles, with mean particle size
      approximately 100 nm, and had an encapsulation efficiency of 97%. The confocal
      microscopy and flow cytometry indicated that the cellular uptake of Lf-PLS was
      significantly higher than that of PEGylated liposome (PLS) in ASGPR-positive
      cells (P<0.05) but not in ASGPR-negative cells (P>0.05). Cytotoxicity assay by
      MTT demonstrated that DOX-loaded Lf-PLS showed significantly stronger
      antiproliferative effects on ASGPR-positive HCC cells than did PLS without the Lf
      modification (P<0.05). The in vivo antitumor studies on male BALB/c nude mice
      bearing HepG2 xenografts demonstrated that DOX-loaded Lf-PLS had significantly
      stronger antitumor efficacy compared with PLS (P<0.05) and free DOX (P<0.05). All
      these results demonstrated that a DOX-loaded Lf-PLS might have great potential
      application for HCC-targeting therapy. 

PMID- 26316747
TI  - Association of electrospinning with electrospraying: a strategy to produce 3D
      scaffolds with incorporated stem cells for use in tissue engineering.
AB  - In tissue engineering, a uniform cell occupation of scaffolds is crucial to
      ensure the success of tissue regeneration. However, this point remains an
      unsolved problem in 3D scaffolds. In this study, a direct method to integrate
      cells into fiber scaffolds was investigated by combining the methods of
      electrospinning of fibers and bioelectrospraying of cells. With the associating
      of these methods, the cells were incorporated into the 3D scaffolds while the
      fibers were being produced. The scaffolds containing cells (SCCs) were produced
      using 20% poly(lactide-co-glycolide) solution for electrospinning and mesenchymal
      stem cells from deciduous teeth as a suspension for bioelectrospraying. After
      their production, the SCCs were cultivated for 15 days at 37 degrees C with an
      atmosphere of 5% CO2. The 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium
      bromide test demonstrated that the cells remained viable and were able to grow
      between the fibers. Scanning electron microscopy showed the presence of a high
      number of cells in the structure of the scaffolds and confocal images
      demonstrated that the cells were able to adapt and spread between the fibers.
      Histological analysis of the SCCs after 1 day of cultivation showed that the
      cells were uniformly distributed throughout the thickness of the scaffolds. Some
      physicochemical properties of the scaffolds were also investigated. SCCs
      exhibited good mechanical properties, compatible with their handling and further
      implantation. The results obtained in the present study suggest that the
      association of electrospinning and bioelectrospraying provides an interesting
      tool for forming 3D cell-integrated scaffolds, making it a viable alternative for
      use in tissue engineering. 

PMID- 26316746
TI  - Nanotechnology for treating osteoporotic vertebral fractures.
AB  - Osteoporosis is a serious public health problem affecting hundreds of millions of
      aged people worldwide, with severe consequences including vertebral fractures
      that are associated with significant morbidity and mortality. To augment or treat
      osteoporotic vertebral fractures, a number of surgical approaches including
      minimally invasive vertebroplasty and kyphoplasty have been developed. However,
      these approaches face problems and difficulties with efficacy and long-term
      stability. Recent advances and progress in nanotechnology are opening up new
      opportunities to improve the surgical procedures for treating osteoporotic
      vertebral fractures. This article reviews the improvements enabled by new
      nanomaterials and focuses on new injectable biomaterials like bone cements and
      surgical instruments for treating vertebral fractures. This article also provides
      an introduction to osteoporotic vertebral fractures and current clinical
      treatments, along with the rationale and efficacy of utilizing nanomaterials to
      modify and improve biomaterials or instruments. In addition, perspectives on
      future trends with injectable bone cements and surgical instruments enhanced by
      nanotechnology are provided. 

PMID- 26316748
TI  - Fiber-optic triggered release of liposome in vivo: implication of personalized
      chemotherapy.
AB  - The aim of this research is to provide proof of principle by applying the fiber
      optic triggered release of photo-thermally responsive liposomes embedded with
      gold nanoparticles (AuNPs) using a 200 MUm fiber with 65 mW and 532 nm excitation
      for topical release in vivo. The tunable delivery function can be paired with an
      apoptosis biosensor based on the same fiber-optic configuration for providing
      real-time evaluation of chemotherapy efficacy in vivo to perform as a
      personalized chemotherapy system. The pattern of topical release triggered by
      laser excitation conveyed through optical fibers was monitored by the increase in
      fluorescence resulting from the dilution of self-quenching (75 mM) fluorescein
      encapsulated in liposomes. In in vitro studies (in 37 degrees C phosphate buffer
      saline), the AuNP-embedded liposomes showed a more efficient triggered release
      (74.53%+/-1.63% in 40 minutes) than traditional temperature-responsive liposomes
      without AuNPs (14.53%+/-3.17%) or AuNP-liposomes without excitation (21.92%+/
      2.08%) by spectroscopic measurements. Using the mouse xenograft studies, we first
      demonstrated that the encapsulation of fluorescein in liposomes resulted in a
      more substantial content retention (81%) in the tumor than for free fluorophores
      (14%) at 120 minutes after administration from in vivo fluorescence imaging.
      Furthermore, the preliminary results also suggested the tunable release
      capability of the system by demonstrating consecutive triggered releases with
      fiber-optic guided laser excitation. 

PMID- 26316749
TI  - In vitro study of novel gadolinium-loaded liposomes guided by GBI-10 aptamer for
      promising tumor targeting and tumor diagnosis by magnetic resonance imaging.
AB  - Novel gadolinium-loaded liposomes guided by GBI-10 aptamer were developed and
      evaluated in vitro to enhance magnetic resonance imaging (MRI) diagnosis of
      tumor. Nontargeted gadolinium-loaded liposomes were achieved by incorporating
      amphipathic material, Gd (III) [N,N-bis-stearylamidomethyl-N'-amidomethyl]
      diethylenetriamine tetraacetic acid, into the liposome membrane using lipid film
      hydration method. GBI-10, as the targeting ligand, was then conjugated onto the
      liposome surface to get GBI-10-targeted gadolinium-loaded liposomes (GTLs). Both
      nontargeted gadolinium-loaded liposomes and GTLs displayed good dispersion
      stability, optimal size, and zeta potential for tumor targeting, as well as
      favorable imaging properties with enhanced relaxivity compared with a commercial
      MRI contrast agent (CA), gadopentetate dimeglumine. The use of GBI-10 aptamer in
      this liposomal system was intended to result in increased accumulation of
      gadolinium at the periphery of C6 glioma cells, where the targeting extracellular
      matrix protein tenascin-C is overexpressed. Increased cellular binding of GTLs to
      C6 cells was confirmed by confocal microscopy, flow cytometry, and MRI,
      demonstrating the promise of this novel delivery system as a carrier of MRI
      contrast agent for the diagnosis of tumor. These studies provide a new strategy
      furthering the development of nanomedicine for both diagnosis and therapy of
      tumor. 

PMID- 26316750
TI  - Codelivery of SH-aspirin and curcumin by mPEG-PLGA nanoparticles enhanced
      antitumor activity by inducing mitochondrial apoptosis.
AB  - Natural product curcumin (Cur) and H2S-releasing prodrug SH-aspirin (SH-ASA) are
      potential anticancer agents with diverse mechanisms, but their clinical
      application prospects are restricted by hydrophobicity and limited efficiency. In
      this work, we coencapsulated SH-ASA and Cur into methoxy poly(ethylene glycol)
      poly (lactide-coglycolide) (mPEG-PLGA) nanoparticles through a modified oil-in
      water single-emulsion solvent evaporation process. The prepared SH-ASA/Cur
      coloaded mPEG-PLGA nanoparticles had a mean particle size of 122.3+/-6.8 nm and
      were monodispersed (polydispersity index =0.179+/-0.016) in water, with high drug
      loading capacity and stability. Intriguingly, by treating with SH-ASA/Cur
      coloaded mPEG-PLGA nanoparticles, obvious synergistic anticancer effects on ES-2
      and SKOV3 human ovarian carcinoma cells were observed in vitro, and activation of
      the mitochondrial apoptosis pathway was indicated. Our results demonstrated that
      SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles could have potential clinical
      advantages for the treatment of ovarian cancer. 

PMID- 26316751
TI  - D-alpha-tocopherol polyethylene glycol succinate-based derivative nanoparticles
      as a novel carrier for paclitaxel delivery.
AB  - Paclitaxel (PTX) is one of the most effective antineoplastic drugs. Its current
      clinical administration Taxol((r)) is formulated in Cremophor EL, which causes
      serious side effects. Nanoparticles (NP) with lower systemic toxicity and
      enhanced therapeutic efficiency may be an alternative formulation of the
      Cremophor EL-based vehicle for PTX delivery. In this study, novel amphipathic 4
      arm-PEG-TPGS derivatives, the conjugation of D-alpha-tocopherol polyethylene
      glycol succinate (TPGS) and 4-arm-polyethylene glycol (4-arm-PEG) with different
      molecular weights, have been successfully synthesized and used as carriers for
      the delivery of PTX. These 4-arm-PEG-TPGS derivatives were able to self-assemble
      to form uniform NP with PTX encapsulation. Among them, 4-arm-PEG(5K)-TPGS NP
      exhibited the smallest particle size, highest drug-loading efficiency, negligible
      hemolysis rate, and high physiologic stability. Therefore, it was chosen for
      further in vitro and in vivo investigations. Facilitated by the effective uptake
      of the NP, the PTX-loaded 4-arm-PEG(5K)-TPGS NP showed greater cytotoxicity
      compared with free PTX against human ovarian cancer (A2780), non-small cell lung
      cancer (A549), and breast adenocarcinoma cancer (MCF-7) cells, as well as a
      higher apoptotic rate and a more significant cell cycle arrest effect at the G2/M
      phase in A2780 cells. More importantly, PTX-loaded 4-arm-PEG(5K)-TPGS NP resulted
      in a significantly improved tumor growth inhibitory effect in comparison to
      Taxol((r)) in S180 sarcoma-bearing mice models. This study suggested that 4-arm
      PEG(5K)-TPGS NP may have the potential as an anticancer drug delivery system.

PMID- 26316752
TI  - Real-time analysis of dual-display phage immobilization and autoantibody
      screening using quartz crystal microbalance with dissipation monitoring.
AB  - Over the last three decades, phage display technology has been used for the
      display of target-specific biomarkers, peptides, antibodies, etc. Phage display
      based assays are mostly limited to the phage ELISA, which is notorious for its
      high background signal and laborious methodology. These problems have been
      recently overcome by designing a dual-display phage with two different end
      functionalities, namely, streptavidin (STV)-binding protein at one end and a
      rheumatoid arthritis-specific autoantigenic target at the other end. Using this
      dual-display phage, a much higher sensitivity in screening specificities of
      autoantibodies in complex serum sample has been detected compared to single
      display phage system on phage ELISA. Herein, we aimed to develop a novel, rapid,
      and sensitive dual-display phage to detect autoantibodies presence in serum
      samples using quartz crystal microbalance with dissipation monitoring as a
      sensing platform. The vertical functionalization of the phage over the STV
      modified surfaces resulted in clear frequency and dissipation shifts revealing a
      well-defined viscoelastic signature. Screening for autoantibodies using antihuman
      IgG-modified surfaces and the dual-display phage with STV magnetic bead complexes
      allowed to isolate the target entities from complex mixtures and to achieve a
      large response as compared to negative control samples. This novel dual-display
      strategy can be a potential alternative to the time consuming phage ELISA
      protocols for the qualitative analysis of serum autoantibodies and can be taken
      as a departure point to ultimately achieve a point of care diagnostic system. 

PMID- 26316753
TI  - Poor mental health status and aggression are associated with poor driving
      behavior among male traffic offenders.
AB  - BACKGROUND: In Iran, traffic accidents and deaths from traffic accidents are
      among the highest in the world, and generally driver behavior rather than either
      technical failures or environmental conditions are responsible for traffic
      accidents. In the present study, we explored the extent to which aggressive
      traits, health status, and sociodemographic variables explain driving behavior
      among Iranian male traffic offenders. METHOD: A total of 443 male driving
      offenders (mean age: M =31.40 years, standard deviation =9.56) from Kermanshah
      (Iran) took part in the study. Participants completed a questionnaire booklet
      covering sociodemographic variables, traits of aggression, health status, and
      driving behavior. RESULTS: Poor health status, such as symptoms of depression,
      anxiety, insomnia, and social dysfunction, and also higher levels of trait
      aggression explained poor driving behavior. Multiple regressions indicated that
      poor health status, but not aggression, independently predicted poor driving
      behavior. CONCLUSION: Results suggest that health status concerns are associated
      with poor driving behavior. Prevention and intervention might therefore focus on
      drivers reporting poor mental health status.

PMID- 26316754
TI  - The structural equation analysis of childhood abuse, adult stressful life events,
      and temperaments in major depressive disorders and their influence on
      refractoriness.
AB  - BACKGROUND: Previous studies have shown the interaction between heredity and
      childhood stress or life events on the pathogenesis of a major depressive
      disorder (MDD). In this study, we tested our hypothesis that childhood abuse,
      affective temperaments, and adult stressful life events interact and influence
      the diagnosis of MDD. PATIENTS AND METHODS: A total of 170 healthy controls and
      98 MDD patients were studied using the following self-administered questionnaire
      surveys: the Patient Health Questionnaire-9 (PHQ-9), the Life Experiences Survey,
      the Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego
      Autoquestionnaire, and the Child Abuse and Trauma Scale (CATS). The data were
      analyzed with univariate analysis, multivariable analysis, and structural
      equation modeling. RESULTS: The neglect scores of the CATS indirectly predicted
      the diagnosis of MDD through cyclothymic and anxious temperament scores of the
      Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego
      Autoquestionnaire in the structural equation modeling. Two temperaments -
      cyclothymic and anxious - directly predicted the diagnosis of MDD. The validity
      of this result was supported by the results of the stepwise multivariate logistic
      regression analysis as follows: three factors - neglect, cyclothymic, and anxious
      temperaments - were significant predictors of MDD. Neglect and the total CATS
      scores were also predictors of remission vs treatment-resistance in MDD patients
      independently of depressive symptoms. LIMITATIONS: The sample size was small for
      the comparison between the remission and treatment-resistant groups in MDD
      patients in multivariable analysis. CONCLUSION: This study suggests that
      childhood abuse, especially neglect, indirectly predicted the diagnosis of MDD
      through increased affective temperaments. The important role as a mediator of
      affective temperaments in the effect of childhood abuse on MDD was suggested.

PMID- 26316755
TI  - Autophagy dysfunction upregulates beta-amyloid peptides via enhancing the
      activity of gamma-secretase complex.
AB  - Numerous studies have shown that autophagy failure plays a critical role in the
      pathogenesis of Alzheimer's disease, including increased expression of beta
      amyloid (Abeta) protein and the dysfunction of Abeta clearance. To further
      evaluate the role of autophagy in Alzheimer's disease, the present study was
      implemented to investigate the effects of autophagy on alpha-secretase, beta
      secretase, or gamma-secretase, and observe the effects of autophagy on autophagic
      clearance markers. These results showed that both autophagy inhibitor and inducer
      enhanced the activity of alpha-, beta-, and gamma-secretases, and Abeta
      production. Autophagy inhibitor may more activate gamma-secretase and promote
      Abeta production and accumulation than its inducer. Both autophagy inhibitor and
      inducer had no influence on Abeta clearance. Hence, autophagy inhibitor may
      activate gamma-secretase and promote Abeta production and accumulation, but has
      no influence on Abeta clearance. 

PMID- 26316756
TI  - Correlation between pain response and improvements in patient-reported outcomes
      and health-related quality of life in duloxetine-treated patients with diabetic
      peripheral neuropathic pain.
AB  - OBJECTIVE: We assessed whether quality of life (QoL) improvement in duloxetine
      treated patients with diabetic peripheral neuropathic pain (DPNP) correlates with
      the extent of pain relief. METHODS: Pooled data from three multicountry, double
      blind, 12-week, placebo-controlled trials of duloxetine-treated (duloxetine 60 mg
      once daily; total number =335) patients with DPNP were analyzed. Based on
      improvement in 24-hour average pain scores, patients were stratified into four
      groups. Improvement in QoL, which was measured as the change from baseline in two
      patient-reported health outcome measures (Short Form [SF]-36 and five-dimension
      version of the EuroQol Questionnaire [EQ-5D]), was evaluated and compared among
      the four groups. Pearson's correlation coefficient was calculated to assess the
      correlation between improvement in pain scores and improvement in QoL. RESULTS:
      The group with more pain improvement generally showed greater mean change from
      baseline in all of the SF-36 scale scores and on the EQ-5D index. Pearson's
      correlation coefficients ranged from 0.114 to 0.401 for the SF-36 scale scores
      (P<0.05), and it was 0.271 for the EQ-5D (P<0.001). CONCLUSION: Improvement in
      pain scores was positively correlated with improvement in QoL and patient
      reported outcomes in duloxetine-treated patients.

PMID- 26316757
TI  - Childhood adversities and laboratory pain perception.
AB  - Childhood adversity has frequently been related to a wide range of psychosomatic
      complaints in adulthood. The present study examined the relationship between
      different forms of childhood adversity and laboratory measures of pain. Heat pain
      tolerance and perceived heat pain intensity were measured in a community-based
      sample of 62 women (aged 20-64 years). Participants completed the Childhood
      Trauma Questionnaire (CTQ), which assesses five forms of childhood adversity:
      physical abuse, sexual abuse, emotional abuse, physical neglect, and emotional
      neglect. Somatic symptoms, depressive symptoms, and pain catastrophizing were
      assessed as potential mediators. Bivariate analyses indicated that emotional
      abuse but no other forms of childhood adversity were significantly related to
      decreased heat pain tolerance (r=-0.27; P<0.05). Accordingly, multiple regression
      analyses revealed that only emotional abuse was a significant predictor of heat
      pain tolerance (beta=-0.62; P=0.034) when entering all CTQ subscales
      simultaneously. Although emotional abuse was also related to somatic symptoms,
      depressive symptoms, and pain catastrophizing, none of these variables mediated
      the relationship between childhood adversity and laboratory pain (P>0.1). No
      significant associations were found between any forms of childhood adversity and
      heat pain intensity. Our findings indicate that the severity of emotional
      childhood abuse is associated with decreased pain tolerance, an affective
      component of pain, but not with heat pain intensity, which has been described as
      a sensory component of pain. 

PMID- 26316758
TI  - Misophonia: current perspectives.
AB  - Misophonia is characterized by a negative reaction to a sound with a specific
      pattern and meaning to a given individual. In this paper, we review the clinical
      features of this relatively common yet underinvestigated condition, with focus on
      co-occurring neurodevelopmental disorders. Currently available data on the
      putative pathophysiology of the condition can inform our understanding and guide
      the diagnostic process and treatment approach. Tinnitus retraining therapy and
      cognitive behavior therapy have been proposed as the most effective treatment
      strategies for reducing symptoms; however, current treatment algorithms should be
      validated in large population studies. At the present stage, competing paradigms
      see misophonia as a physiological state potentially inducible in any subject, an
      idiopathic condition (which can present with comorbid psychiatric disorders), or
      a symptomatic manifestation of an underlying psychiatric disorder. Agreement on
      the use of standardized diagnostic criteria would be an important step forward in
      terms of both clinical practice and scientific inquiry. Areas for future research
      include phenomenology, epidemiology, modulating factors, neurophysiological
      underpinnings, and treatment trials. 

PMID- 26316759
TI  - Employment and the associated impact on quality of life in people diagnosed with
      schizophrenia.
AB  - A systematic review was conducted to assess the employment rate of people with
      schizophrenia. Additionally, information from the selected studies concerning
      factors associated with employment and health-related quality of life (HRQoL) was
      examined. Employment rates ranged from 4% to 50.4%. The studies differed
      considerably in design, patient settings, and methods of recruitment. The most
      frequently reported factors associated with employment were negative and
      cognitive symptoms, age of onset, and duration and course of the disease.
      Individual characteristics associated with unemployment were older age, lower
      education, and sex (female). Additionally, environmental factors, eg, the
      availability of welfare benefits and vocational support programs, seemed to play
      a role. Generally, being employed was positively associated with HRQoL. However,
      the causal direction of this association remained unclear, as studies on the
      bidirectional relationship between employment and HRQoL were lacking. 

PMID- 26316760
TI  - Lurasidone for the treatment of bipolar depression: an evidence-based review.
AB  - Bipolar disorder (BD) is a debilitating and difficult-to-treat psychiatric
      disease that presents a serious burden to patients' lives as well as health care
      systems around the world. The essential diagnostic criterion for BD is episodes
      of mania or hypomania; however, the patients report that the majority of their
      time is spent in a depressive phase. Current treatment options for this component
      of BD have yet to achieve satisfactory remission rates. Lurasidone is a drug in
      the benzisothiazole class approved by the US Food and Drug Administration in June
      2013 for the acute treatment of bipolar depression. Its pharmacological profile
      features high-affinity antagonism at D2, 5-HT2A, and 5-HT7 receptors; moderate
      affinity antagonism at alpha2C-adrenergic receptors; low- to very low-affinity
      antagonism at alpha1A-adrenergic, alpha2A-adrenergic, H1, M1, and 5-HT2C
      receptors; and high-affinity partial agonism at 5-HT1A. Preliminary findings from
      two recent double-blinded clinical trials suggest that lurasidone is efficacious
      in treating bipolar I depression, with clinical effects manifesting as early as
      the first 2-3 weeks of treatment (as measured by the Montgomery-Asberg Depression
      Rating Scale and Clinical Global Impressions Scale for use in bipolar illness).
      Its therapeutic benefit appears to be comparable to the current US Food and Drug
      Administration-indicated treatments: quetiapine and olanzapine-fluoxetine,
      according to a measure of effect size known as number needed to treat. These
      studies reported relatively limited extrapyramidal and metabolic side effects as
      a result of treatment with lurasidone, with the most common side effect being
      nausea. Safety data drawn from these studies, as well as a more extensive body of
      schizophrenia research, indicate that in comparison with other atypical
      antipsychotics, treatment with lurasidone is less likely to result in metabolic
      side effects such as weight gain or disturbances of serum glucose or lipid
      levels. Lurasidone holds clinical potential as a novel, efficacious
      pharmacological treatment for bipolar depression. However, current data on its
      use for the treatment of BD are limited, and more extensive research, both longer
      in duration as well as independently conducted, is needed. 

PMID- 26316761
TI  - Psychiatric symptoms and leptin in obese patients who were bariatric surgery
      candidates.
AB  - OBJECTIVE: There is a significant relationship between obesity and common mental
      symptoms (depression and anxiety symptoms). But the association between
      depression (or anxiety symptoms) and serum leptin is still unclear and
      controversial, despite the growing body of evidence supporting the existence of
      "leptin resistance" in obese persons. So we investigated whether common mental
      symptoms, obesity, and the interactive effect of these two factors have a
      relationship with leptin in obese patients who were candidates for bariatric
      surgery. METHODS: In all, 139 participants (mean age: 31.4 years, standard
      deviation: 9.3 years, 73.4% female) were enrolled at an obesity treatment center
      in southern Taiwan. Serum leptin levels and body mass index (BMI) were measured.
      The Chinese Health Questionnaire and Taiwanese Depression Questionnaire were
      administered. RESULTS: The mean BMI of our participants was 39.4 kg/m(2) (+/
      6.8), and the mean leptin level was 24.5 ng/mL (+/-9.4). In the multivariate
      regression models, Chinese Health Questionnaire-by-BMI and Taiwanese Depression
      Questionnaire-by-BMI interaction terms remained significant predictors of leptin
      level (beta=0.16, P<0.0001; beta=0.04, P<0.0001, respectively), after adjustment
      for age, sex, and history of hypertension, diabetes, and hyperlipidemia, despite
      the inverse correlation between Chinese Health Questionnaire (or Taiwanese
      Depression Questionnaire) and leptin. In addition, female patients had
      significantly higher leptin levels than male patients. CONCLUSION: The present
      findings confirmed that the relationship between common mental symptoms and
      leptin is modulated by obesity in severely obese patients. Future studies should
      focus on further measures of leptin receptors or signaling on the basis of these
      interactive effects in psychiatry.

PMID- 26316762
TI  - Intern doctors' views on the current and future antibiotic resistance situation
      of Chattagram Maa O Shishu Hospital Medical College, Bangladesh.
AB  - BACKGROUND: Bacterial resistance due to antibiotic misuse is reported every day.
      Such threat calls for a consensus to develop new strategies to prevent the
      development of antibiotic resistance of bacteria. Medical doctors must play a
      pivotal role to control and prevent the misuse of antibiotics. There were
      complaints that prescribers are lacking behind in updates and advancement in the
      field. To address such knowledge gap, a study was conducted to know the views of
      interns on the current antibiotic resistance situation in a teaching hospital in
      Bangladesh. METHODS: This study was a cross-sectional, randomized, and
      questionnaire-based survey. Interns of the medicine, gynecology, and surgery
      departments of Chattagram Maa O Shishu Hospital Medical College were the study
      population. RESULTS: Out of 50 respondents, 98% would like more education on
      antibiotic selection. All respondents believed that prescribing inappropriate or
      unnecessary antibiotics was professionally unethical. Ninety percent of the
      participants were confident in making an accurate diagnosis of infection. Eighty
      four percent of them were confident about dosage schedule. In all, 98%
      participants thought that antibiotic resistance is a national problem and 64% of
      the respondents thought that same problem also existed in their hospital. Study
      participants were of the view that 41%-60% of antibiotic usages are irrational in
      Bangladesh. Fifty-eight percent of the study population thought that
      antimicrobial resistance (AR) would be a greater problem in the future.
      CONCLUSION: The interns believe that there is a knowledge gap on AR. More
      emphasis should be given to AR and its implications in the undergraduate
      curriculum. Latest national and international guidelines for antimicrobial
      therapy and resistance should be made available to the interns.

PMID- 26316763
TI  - The relationship between eosinophilia and slow coronary flow.
AB  - AIM: The pathophysiology of slow coronary flow (SCF) involves atherosclerosis,
      small vessel dysfunction, platelet function disorders, and inflammation. It has
      been known that eosinophils also play a significant role in inflammation,
      vasoconstriction, thrombosis, and endothelial dysfunction. We propose to evaluate
      the relationship between eosinophilia and SCF. METHODS: All patients who
      underwent coronary angiography between January 2011 and December 2013 were
      screened retrospectively. Of 6,832 patients, 102 patients with SCF (66 males,
      mean age 52.2+/-11.7 years) and 77 control subjects with normal coronary
      angiography (50 males, mean age 50.7+/-8.1 years) were detected. Baseline
      characteristics, hematological test results, and biochemical test results were
      obtained from the hospital database. RESULTS: Baseline characteristics of the
      study groups were comparable between groups. There was no significant difference
      between groups regarding leukocyte count, paletelet count, and mean platelet
      volume. However, patients with SCF had a higher eosinophil count than the
      controls (0.24+/-0.17*10(3)/MUL vs 0.16+/-0.15*10(3)/MUL, P=0.002). In addition,
      eosinophil count was found to be correlated with thrombolysis in myocardial
      infarction (TIMI) frame count in the SCF group (r=0.3, P<0.01). There was no
      significant correlation between eosinophil count and the number of coronary
      arteries showing slow flow. CONCLUSION: Patients with SCF have higher blood
      eosinophil count, and this may play an important role in the pathogenesis of SCF.
      Elevated baseline eosinophil count may indicate the presence of SCF.

PMID- 26316765
TI  - Comparison of outcomes of laparoscopic intracorporeal knotting technique in
      patients with complicated and noncomplicated acute appendicitis.
AB  - BACKGROUND AND AIM: In our study we aimed to compare laparoscopic intracorporeal
      knotting technique (base of the appendix was ligated with 20 cm of 2.0 silk) in
      patients with complicated acute appendicitis (CAA) and noncomplicated acute
      appendicitis. PATIENTS AND METHODS: Ninety patients (female/male: 40/50, age
      ranging from 16 to 60 years, median age and interquartile range [IQR]: 25 [20;
      32] years) who underwent laparoscopic appendectomy were included in the study.
      The patients were evaluated for the type of acute appendicitis, duration of
      operation, duration of hospital stay, and postoperative complications. RESULTS:
      The number of cases diagnosed as CAA was 28 (31.1%), and the number of
      noncomplicated cases was 62 (68.9%). We found that there was no significant
      difference in postoperative complication rates between complicated and
      noncomplicated appendicitis cases. Incision site infection was seen in seven
      cases (7.8%) and ileus was seen in two cases (2.2%). Bleeding, intra-abdominal
      abscess, and appendix stump leakage were not observed in any of the cases. Median
      and IQR duration of operation were 42 (35; 52) minutes and median and IQR
      duration of hospital stay were detected as 2 (1; 2) (range 1-10) days.
      CONCLUSION: Laparoscopic intracorporeal knotting technique may be a safe,
      effective, and reliable technique as the materials needed for closing the
      appendix stumps are easily available for both CAA cases and noncomplicated cases.

PMID- 26316764
TI  - Profile of vortioxetine in the treatment of major depressive disorder: an
      overview of the primary and secondary literature.
AB  - This article reviews the pharmacological profile and available efficacy and
      tolerability/safety data for vortioxetine, one of the most recent antidepressant
      drugs to be approved in the USA for the treatment of major depressive disorder
      (MDD) in adults. The efficacy of vortioxetine for treating MDD in adults is
      supported by eight positive short-term (6- to 12-weeks) randomized, placebo
      controlled trials, and one positive randomized, double-blind, 52-week relapse
      prevention trial. Based on pooled data from short-term randomized trials and from
      longer-term studies, vortioxetine appears to be well tolerated and to have a low
      incidence of adverse effects on sexual functioning. Vortioxetine also appears to
      be effective for treating symptoms of MDD in the elderly based on the results of
      one randomized trial for which recruitment was focused on this specific
      population. Nevertheless, effectiveness studies that directly compare the
      clinical effects of vortioxetine with other established antidepressant drugs are
      lacking, and there is no evidence as yet that vortioxetine is more clinically
      effective than other types of antidepressants. Some preliminary suggestions
      concerning the place of vortioxetine among the broad range of pharmacological
      treatments for adults with MDD are provided. 

PMID- 26316766
TI  - Appendectomy in a child with cyclic neutropenia in profound neutropenic episode.
AB  - Our experience in the treatment of a 4-year-old boy with cyclic neutropenia who
      was admitted for urgent appendectomy is described. The postoperative course was
      uneventful with high daily doses of granulocyte colony-stimulating factor and
      antimicrobial therapy. The purpose of this report is to highlight the importance
      of immediate appendectomy in neutropenic patients, wherein low absolute
      neutrophil count should not be considered as a contraindication for urgent
      surgical procedure. 

PMID- 26316768
TI  - Patient considerations in the management of ulcerative colitis - role of
      vedolizumab.
AB  - Ulcerative colitis (UC) is a subtype of inflammatory bowel disease which causes
      inflammation of the large intestine and affects approximately 7.6-24.6 per
      100,000 persons. The therapeutic goal for UC patients is inducing remission,
      maintaining remission, and ideally, obtaining mucosal healing. Vedolizumab,
      approved by the US Food and Drug Administration in May 2014 for the treatment of
      moderate-to-severe UC and Crohn's disease, is a newly developed anti-integrin
      therapy. This review focuses on the preclinical development of vedolizumab and
      data from early trials, and details the results of the landmark trails that led
      to its approval in the USA with a specific focus on the management of UC.
      Additionally, data on safety and the current UC management protocols are also
      discussed. 

PMID- 26316769
TI  - Value of serial platelet indices measurements for the prediction of pulmonary
      embolism in patients with deep venous thrombosis.
AB  - BACKGROUND: To date, no validated biomarkers with high sensitivity and
      specificity have been established for diagnosis of pulmonary embolism (PE) in
      patients with deep venous thrombosis (DVT). There is a need to develop simple and
      reliable noninvasive tests that can accurately identify patients with PE, even in
      small hospitals or clinics. The aim of this study was to investigate the value of
      mean platelet volume (MPV) and platelet distribution width (PDW) for predicting
      occurrence of PE in patients with DVT. METHODS: Records of acute DVT patients
      were reviewed retrospectively. Group 1 consisted of 50 patients with acute DVT
      and group 2 consisted of 50 patients with acute DVT who developed PE during
      follow-up. The control group consisted of patients with uncomplicated primary
      varicose veins of the lower limbs. Venous peripheral blood samples for
      measurement of MPV, PDW, and platelet count were drawn on admission, before the
      treatment, and at the time of PE diagnosis. RESULTS: MPV and PDW levels at the
      time of PE diagnosis were higher in group 2 than group 1 (P<0.001 and P=0.026,
      respectively). Receiver operating characteristics analysis revealed that a 5.2%
      increase in admission PDW during follow-up provided 70% sensitivity and 82%
      specificity (area under the curve, 0.80), and a 6.6% increase in admission MPV
      during follow-up provided 74% sensitivity and 83% specificity (area under the
      curve, 0.84) for prediction of PE occurrence in patients with DVT. PDW and MPV
      levels at the time of PE diagnosis were found to be independent risk factors for
      the occurrence of PE in patients with DVT. CONCLUSION: Serial measurements of MPV
      and PDW, and percent change in MPV and PDW appears to be a useful marker for
      predicting occurrence of acute PE in patients with a first episode of acute
      proximal DVT.

PMID- 26316767
TI  - Pulmonary hypertension: diagnostic and therapeutic challenges.
AB  - Pulmonary hypertension (PH) is a hemodynamic and pathophysiologic state that can
      be found in multiple conditions with associated symptoms of dyspnea, decreased
      exercise tolerance, and progression to right heart failure. The World Health
      Organization has classified PH into five groups. The first group is pulmonary
      arterial hypertension (PAH), which can be idiopathic, heritable, due to drugs and
      toxins, or associated with conditions such as connective tissue diseases,
      congenital heart disease, portal hypertension, and others. The development of PAH
      is believed to result from smooth muscle cells and endothelial dysfunction that
      impairs production of vasodilators, including nitric oxide and prostacyclin. The
      importance of distinguishing this group from the other groups of PH is that there
      are PAH-specific drugs that target the molecular pathways that are pathogenic in
      the vascular derangements, leading to arterial hypertension, which should not be
      used in the other forms of PH. Other groups of PH include PH due to left heart
      disease, lung disease, chronic thromboembolic disease, as well as a miscellaneous
      category. Echocardiography is used to screen for PH and has varying sensitivity
      and specificity in detecting PH. Additionally, the right heart pressures
      estimated during echocardiogram often differ from those obtained during
      confirmatory testing with right heart catheterization. The most challenging PH
      diagnosis is in a case that does not fit one group of PH, but meets criteria that
      overlap between several groups. This also makes the treatment challenging because
      each group of PH is managed differently. This review provides an overview of the
      five groups of PH and discusses the diagnostic and therapeutic challenges of
      each. 

PMID- 26316770
TI  - Assessing the risk of recurrent venous thromboembolism--a practical approach.
AB  - Recurrent venous thromboembolism (VTE) is associated with increased morbidity and
      mortality. This risk is lowered by anticoagulation, with a large effect in the
      initial phase following the venous thromboembolic event, and with a smaller
      effect in terms of secondary prevention of recurrence when extended
      anticoagulation is performed. On the other hand, extended anticoagulation is
      associated with an increased risk of major bleeding and thus leads to morbidity
      and mortality. Therefore, it is necessary to assess the risk of recurrence for
      VTE on an individual basis, and a recommendation for secondary prophylaxis should
      be specifically based on risk calculation of recurrence of VTE and bleeding. In
      this review, we provide a comprehensive summary of relevant risk factors for
      recurrent VTE and a practical approach for assessing the risk of recurrence in
      daily practice. 

PMID- 26316771
TI  - Prevention of venous thromboembolism in patients undergoing bariatric surgery.
AB  - Bariatric surgical procedures are now a common method of obesity treatment with
      established effectiveness. Venous thromboembolism (VTE) events, which include
      deep vein thrombosis and pulmonary embolism, are an important source of
      postoperative morbidity and mortality among bariatric surgery patients. Due to an
      understanding of the frequency and seriousness of these complications, bariatric
      surgery patients typically receive some method of VTE prophylaxis with lower
      extremity compression, pharmacologic prophylaxis, or both. However, the optimal
      approach in these patients is unclear, with multiple open questions. In
      particular, strategies of adjusted-dose heparins, postdischarge anticoagulant
      prophylaxis, and the role of vena cava filters have been evaluated, but only to a
      limited extent. In contrast to other types of operations, the literature
      regarding VTE prophylaxis in bariatric surgery is notable for a dearth of
      prospective, randomized clinical trials, and current professional guidelines
      reflect the uncertainties in this literature. Herein, we summarize the available
      evidence after systematic review of the literature regarding approaches to VTE
      prevention in bariatric surgery. Identification of risk factors for VTE in the
      bariatric surgery population, analysis of the effectiveness of methods used for
      prophylaxis, and an overview of published guidelines are presented. 

PMID- 26316772
TI  - Subcutaneous adipose tissue plays a beneficial effect on subclinical
      atherosclerosis in young survivors of acute lymphocytic leukemia.
AB  - PURPOSE: The aim of this study was to evaluate the relationship between body
      composition, metabolic profile, adipokines, and carotid intima-media thickness
      (cIMT) in young survivors of childhood acute lymphocytic leukemia (ALL). PATIENTS
      AND METHODS: This cross-sectional study compared 55 ALL survivors, of
      chronological age between 15 years and 24 years, assigned into two groups
      according to the exposure to cranial radiation therapy (CRT; 25 irradiated and 30
      nonirradiated) with 24 leukemia-free controls, and assessed body fat mass (dual
      energy X-ray absorptiometry), computed tomography scan-derived abdominal adipose
      tissue, lipid profile, blood pressure (BP), adipokines, and cIMT by a multiple
      regression analysis. RESULTS: Treatment with CRT had an effect on all of the
      variables derived from the computed tomography scan: visceral adipose tissue
      (VAT) and subcutaneous adipose tissue (SAT) (P<0.050). In a multiple linear
      regression model, cIMT positively correlated with exposure to CRT (P=0.029),
      diastolic BP (P=0.016), and leptin-to-adiponectin ratio (P=0.048), while
      negatively related to SAT (P=0.007). CONCLUSION: In young survivors of childhood
      ALL, CRT modified the distribution of fat and played a critical role in
      determining cIMT. Leptin-to-adiponectin ratio, a biomarker of abdominal obesity
      and metabolic syndrome, and diastolic BP also influenced cIMT, a marker of
      subclinical atherosclerosis. Nonetheless, adiposity-associated vascular disease
      might be attenuated by SAT. Changes in body fat must be evaluated in this group
      of patients in the early course of survivorship in order to avoid premature
      cardiovascular disease associated with atherosclerosis. Yet, further research as
      regards the possible protective effect of SAT on vascular disease is warranted.

PMID- 26316773
TI  - Nonvitamin K antagonist oral anticoagulants (NOACs): the tide continues to come
      in.

PMID- 26316774
TI  - A multidisciplinary approach to scars: a narrative review.
AB  - The purpose of this article is to carry out a narrative review regarding the
      approach to scars through complementary and alternative medicine focusing on
      osteopathy, naturopathy, and other minor methods and traditional rehabilitative
      medicines, such as physiotherapy and manual therapies. We analyzed the existing
      literature regarding the possible influences of techniques relaxing the diaphragm
      - both manual and psychophysical relaxing techniques - and the consequent local
      response to events leading to scar tissue healing. The objective of the study is
      to become a useful instrument of knowledge for those manual therapists and
      professionals who deal with patients affected by discontinuity of the skin
      surface due to trauma or surgery. This article also intends to stimulate research
      in order to find and propose new methods of scar treatment, taking into
      consideration the information gained so far from other complementary and
      alternative disciplines. 

PMID- 26316775
TI  - Adaptive practices in heart failure care teams: implications for patient-centered
      care in the context of complexity.
AB  - BACKGROUND: Heart failure (HF), one of the three leading causes of death, is a
      chronic, progressive, incurable disease. There is growing support for integration
      of palliative care's holistic approach to suffering, but insufficient
      understanding of how this would happen in the complex team context of HF care.
      This study examined how HF care teams, as defined by patients, work together to
      provide care to patients with advanced disease. METHODS: Team members were
      identified by each participating patient, generating team sampling units (TSUs)
      for each patient. Drawn from five study sites in three Canadian provinces, our
      dataset consists of 209 interviews from 50 TSUs. Drawing on a theoretical framing
      of HF teams as complex adaptive systems (CAS), interviews were analyzed using the
      constant comparative method associated with constructivist grounded theory.
      RESULTS: This paper centers on the dominant theme of system practices, how HF
      care delivery is reported to work organizationally, socially, and practically,
      and describes two subthemes: "the way things work around here", which were
      commonplace, routine ways of doing things, and "the way we make things work
      around here", which were more conscious, effortful adaptations to usual practice
      in response to emergent needs. An adaptive practice, often a small alteration to
      routine, could have amplified effects beyond those intended by the innovating
      team member and could extend to other settings. CONCLUSION: Adaptive practices
      emerged unpredictably and were variably experienced by team members. Our study
      offers an empirically grounded explanation of how HF care teams self-organize and
      how adaptive practices emerge from nonlinear interdependencies among diverse
      agents. We use these insights to reframe the question of palliative care
      integration, to ask how best to foster palliative care-aligned adaptive practices
      in HF care. This work has implications for health care's growing challenge of
      providing care to those with chronic medical illness in complex, team-based
      settings.

PMID- 26316777
TI  - Urine microRNAs as biomarkers for bladder cancer: a diagnostic meta-analysis.
AB  - BACKGROUND: The diagnostic value of microRNA (miRNA) detection in patients with
      bladder cancer (BCa) is controversial. We performed a diagnostic meta-analysis to
      evaluate current evidence on the use of miRNA assays to diagnose BCa. METHODS: We
      systematically searched PubMed, Embase, and Web of Science for studies published
      before March 31, 2015. The pooled sensitivity, specificity, positive and negative
      likelihood ratios, diagnostic odds ratio, and area under the curve (AUC) were
      calculated to evaluate the overall test performance. Subgroup analyses were used
      to explore the between-study heterogeneity. Deeks' funnel plot asymmetry test was
      used to test publication bias. We applied the software of RevMan 5.2 and Stata
      11.0 to the meta-analysis. RESULTS: A total of 23 studies from nine articles were
      included in the meta-analysis, with a total of 719 patients and 494 controls. The
      pooled sensitivity and specificity were 0.75 (95% confidence interval [CI], 0.68
      0.80) and 0.75 (95% CI, 0.70-0.80), respectively. The pooled positive likelihood
      ratio was 3.03 (95% CI, 2.50-3.67); negative likelihood ratio was 0.33 (95% CI,
      0.27-0.42); and diagnostic odds ratio was 9.07 (95% CI, 6.35-12.95). The pooled
      AUC was 0.81 (95% CI, 0.78-0.85). Subgroup analyses indicated that the multiple
      miRNAs assays and urine supernatant assays showed high accuracies in diagnosing
      BCa. CONCLUSION: The miRNA assays may serve as potential noninvasive diagnostic
      tool for the detection of BCa. However, the clinical application of miRNA assays
      for BCa diagnosis still needs further validation by large prospective studies.

PMID- 26316778
TI  - A recurrent ovarian cancer patient with a history of nine prior chemotherapy
      regimens who was safely treated with weekly paclitaxel plus bevacizumab and
      achieved a complete response: a case report.
AB  - Herein, we describe our experience with a recurrent ovarian cancer patient who
      was treated safely with bevacizumab and who achieved a complete response despite
      receiving nine prior chemotherapy regimens. The patient was a 54-year-old woman
      with stage IIIC recurrent ovarian serous adenocarcinoma (grade 3). Computed
      tomography (CT) revealed that no evidence of ascites, multiple intraperitoneal
      dissemination, or intrapelvic lymph node metastases was present. The absence of
      bowel obstruction and disseminated lesions involving the intestinal tract was
      confirmed by CT. Performance status was 0, and a blood test also indicated
      preservation of major organ function. In our hospital, weekly paclitaxel plus
      bevacizumab therapy (paclitaxel at 80 mg/m(2) on days 1, 8, and 15; bevacizumab
      at 15/mg/kg on day 1 and every 21 days thereafter) was started. Eight cycles were
      administered, with no signs of gastrointestinal perforation, and the antitumor
      effect was evaluated as a complete response. The observed adverse events included
      grade 1 hyponatremia and grade 1 hypochloremia, and there was one grade 1 sensory
      peripheral neuropathy. These adverse events neither delayed treatment nor
      necessitated any dosage reductions. This case suggests that bevacizumab can be
      safely administered even to patients with recurrent ovarian cancer who have
      received three or more prior chemotherapy regimens if there are neither symptoms
      of bowel obstruction nor lesions suggestive of intestinal invasion on diagnostic
      imaging. 

PMID- 26316776
TI  - Inactivity of imatinib in gastrointestinal stromal tumors (GISTs) harboring a KIT
      activation-loop domain mutation (exon 17 mutation pN822K).
AB  - The development of gastrointestinal stromal tumors (GISTs) is largely driven by
      mutations in the KIT and PDGFRalpha genes. Imatinib mesylate is an oral small
      molecular tyrosine kinase inhibitor that mainly targets abl, c-KIT, and
      PDGFRalpha. Imatinib achieves disease control in approximately 70%-85% of
      patients with advanced GIST, and the median progression-free survival is 20-24
      months. The efficacy of imatinib correlates with tumor kinase mutational status
      (exon 11 mutations mainly), and some mutations are known to be responsible for
      primary and secondary imatinib resistance. Beyond these, there are many other
      mutations that are considered rare and are associated with unknown clinical
      behavior. In the literature, there are poor and inconsistent data about the
      inhibitor sensitivity of mutations occurring in the activation-loop domain
      encoded by exon 17. In this article, we focus on a case of a patient suffering
      from GIST, harboring an extremely rare KIT activation-loop domain mutation (exon
      17 mutation pN822K) treated with imatinib. A review of the literature is also
      presented. 

PMID- 26316779
TI  - Hepatoma-derived growth factor predicts unfavorable prognosis of epithelial
      ovarian cancer.
AB  - AIM: To evaluate the expression and clinical significance of hepatoma-derived
      growth factor (HDGF) in epithelial ovarian cancer (EOC). BACKGROUND: Recent
      studies have demonstrated that HDGF overexpression correlates to the progression
      and poor prognosis in several kinds of cancers. However, the clinical
      significance and prognostic value of HDGF in EOC have not been investigated.
      METHODS: Expression of HDGF was visualized by immunohistology and then the cohort
      was divided into higher- and lower-expression groups. The correlation between
      HDGF and clinicopathologic factors was analyzed by chi (2) test. The prognostic
      value of HDGF was assessed by univariate analysis with Kaplan-Meier method, and
      by multivariate analysis with Cox-regression model. With experiments in vitro,
      HDGF expression in ovarian cancer cell lines was detected by immunoblotting.
      RESULTS: Higher HDGF expression rate was 52.76% in EOC. HDGF expression was
      significantly associated with lymphatic metastasis (P=0.006). Higher HDGF
      expression was closely correlated to poorer 5-year overall survival rate with
      univariate analysis (P=0.003), and was identified as an independent prognostic
      factor with multivariate analysis (P=0.007). With experiments in vitro, HDGF was
      proved to exist in all ovarian cancer cell lines with different expression
      levels. CONCLUSION: HDGF expression correlates to unfavorable prognosis and can
      be considered as an independent prognostic factor, indicating that HDGF may be a
      promising potential molecular drug target.

PMID- 26316780
TI  - CAG repeat polymorphisms in the androgen receptor and breast cancer risk in
      women: a meta-analysis of 17 studies.
AB  - The association between polymorphic CAG repeats in the androgen receptor gene in
      women and breast cancer susceptibility has been studied extensively. However, the
      conclusions regarding this relationship remain conflicting. The purpose of this
      meta-analysis was to identify whether androgen receptor CAG repeat lengths were
      related to breast cancer susceptibility. The MEDLINE, PubMed, and EMBASE
      databases were searched through to December 2014 to identify eligible studies.
      Data and study quality were rigorously assessed by two investigators according to
      the Newcastle-Ottawa Quality Assessment Scale. The publication bias was assessed
      by the Begg's test. Seventeen eligible studies were included in this meta
      analysis. The overall analysis suggested no association between CAG polymorphisms
      and breast cancer risk (odds ratio [OR] 1.031, 95% confidence interval [CI] 0.855
      1.245). However, in the subgroup analysis, we observed that long CAG repeats
      significantly increased the risk of breast cancer in the Caucasian population (OR
      1.447, 95% CI 1.089-1.992). Additionally, the risk was significantly increased in
      Caucasian women carrying two alleles with CAG repeats >=22 units compared with
      those with two shorter alleles (OR 1.315, 95% CI 1.014-1.707). These findings
      suggest that long CAG repeats increase the risk of breast cancer in Caucasian
      women. However, larger scale case-control studies are needed to validate our
      results. 

PMID- 26316781
TI  - Alteration of ASIC1 expression in clear cell renal cell carcinoma.
AB  - BACKGROUND: Acidic extracellular pH is a major feature of tumor tissue. Acid
      sensing ion channels (ASICs) represent an H(+)-gated subgroup of the
      degenerin/epithelial Na(+) channel family and are activated by acidic
      microenvironment. Little is known about the expression and clinical significance
      of ASICs in solid tumors. The purpose of this study was to examine the expression
      of ASIC1 in human clear cell renal cell carcinoma (CCRCC) and to determine if the
      expression of ASIC1 is associated with clinicopathological features. METHODS: The
      expression of ASIC1 in CCRCC tissues at the mRNA and protein levels was
      determined by real-time quantitative polymerase chain reaction and Western blot
      analysis, respectively. A tissue microarray was used to assess the expression of
      ASIC1 protein in tumor tissue and matched adjacent normal tissues from 75
      patients with CCRCC. RESULTS: ASIC1 expression was detected in normal renal and
      CCRCC samples. The expressions of ASIC1 protein and mRNA were significantly
      decreased in the CCRCC tissues compared with matched normal renal tissues
      (P<0.05). The staining density measurement showed that the expression of ASIC1
      was significantly decreased in stage I (P=0.037), stage II (P=0.026), and stage
      III (P=0.026), grades I-II CCRCC (P=0.004), and CCRCC from male patients
      (P=0.00002). However, no significant difference was observed for ASIC1 expression
      between CCRCC and normal tissue in patients with stage IV CCRCC (P=0.236),
      patients with grades III-IV CCRCC (P=0.314), and female patients (P=0.095).
      Spearman correlations demonstrated that ASIC1 expression did not correlate to
      tumor stage (correlation coefficient [CC =0.168], P=0.149) and the age of
      patients (CC -0.147, P=0.688) but showed a positive correlation to higher tumor
      grades (CC =0.270, P=0.018). CONCLUSION: ASIC1 is downregulated in CCRCC. ASIC1
      expression may be potentially used as a novel biomarker and even a CCRCC
      therapeutic target. Further efforts will be made to clarify the mechanism of
      ASIC1 in occurrence, progression, and metastasis of CCRCC.

PMID- 26316782
TI  - Simultaneous hepatectomy and splenectomy versus hepatectomy alone for
      hepatocellular carcinoma complicated by hypersplenism: a meta-analysis.
AB  - BACKGROUND: This study systematically compared the efficacy and safety of
      simultaneous hepatectomy and splenectomy (HS) with hepatectomy (H) alone in
      patients with hepatocellular carcinoma (HCC) and hypersplenism. METHODS: The
      PubMed, Web of Science, Science Direct, EMBASE, and Cochrane Library databases
      were systematically searched by two independent researchers through to March 31,
      2015 to identify relevant studies. All the extracted literature were managed by
      Bibliographic citation management software. Quality assessment of the included
      studies was performed using a modified Newcastle-Ottawa Scale judgment. The data
      were analyzed using RevMan5.2 software. RESULTS: Eight studies including a total
      of 761 patients with HCC and hypersplenism (360 in the HS group, 401 in the H
      group) were finally included in the analysis. Outcomes, including postoperative
      complications, perioperative mortality, operation time, 5-year survival rate, and
      need for blood transfusion did not differ significantly between the two groups.
      HS was associated with significantly more intraoperative bleeding (mean
      difference [MD] 57.15, 95% confidence interval [CI] 18.83-95.46, P=0.003), and
      CD4/CD8 ratio (MD 0.69, 95% CI 0.61-0.77, P<0.00001), CD4 subset, platelet count
      (MD 213.06, 95% CI 202.59-223.53, P<0.0001), white blood cell count (MD 4.85, 95%
      CI 4.58-5.13, P<0.0001), interferon-gamma levels (MD 18.52, 95% CI 13.93-23.11,
      P<0.00001), and interleukin-2 levels (MD 20.73, 95% CI 16.05-25.41, P<0.0001). In
      addition, lower CD8 subset (MD -7.85, 95% CI -9.07, -6.63, P<0.00001) and
      interleukin-10 levels (MD -18.56, 95% CI -22.61, -14.50, P<0.00001) were observed
      for HS. CONCLUSION: We identified that simultaneous HS do not increase
      postoperative complications, operation time, or perioperative mortality in
      patients with HCC and hypersplenism. Simultaneous splenectomy can increase
      postoperative white blood cell and platelet counts significantly, improve blood
      coagulation, reduce the incidence of postoperative bleeding, and enhance
      immunity. Therefore, HS is safe, effective, and feasible for patients with HCC
      and hypersplenism.

PMID- 26316783
TI  - Clinical efficacy of percutaneous vertebroplasty combined with intensity
      modulated radiotherapy for spinal metastases in patients with NSCLC.
AB  - OBJECTIVE: This study aimed to evaluate the safety and efficacy of percutaneous
      vertebroplasty (PVP) combined with intensity-modulated radiotherapy (IMRT) for
      metastatic lesions of patients with non-small-cell lung cancer (NSCLC) at centrum
      vertebrae. METHODS: A total of 39 patients with spinal metastatic NSCLC (stage
      IV) were treated with PVP followed by IMRT (30 Gy/10F/2 W) for metastatic lesion
      at centrum vertebrae under local anesthesia. Retrospective analysis was done with
      medical records and radiological data. The change of visual analog scale (VAS),
      activities of daily living, and kyphotic angle was measured preoperatively. The
      presence of complications was assessed preoperatively (baseline) at 24 hours, 1
      week, and 1, 3, 6, 12, and 24 months postoperatively, or until the patient died
      or was lost to follow-up. Survival was assessed in the group. RESULTS: A total of
      39 consecutive patients were successfully treated with PVP via a translateral
      approach and IMRT. Their mean VAS score decreased from 7.93+/-1.09 preoperatively
      to 4.14+/-1.15 by the 24-hour postoperative time point and was 3.92+/-1.23 at 1
      week, 4.27+/-1.93 at 1 month, 3.24+/-1.35 at 3 months, 2.27+/-0.96 at 6 months,
      and 2.59+/-1.55 at 12 months after the procedure. The mean VAS score at all of
      the postoperative time points was decreased significantly from the preoperative
      baseline score (P<0.05). Activities of daily living evaluation showed that the
      patients had a significantly high life quality after the combined approach
      (50.9+/-11.7 vs 82.3+/-9.9, P<0.05). No severe complications were observed. Mild
      complications included two cases (5.13%) of asymptomatic cement leakage into the
      epidural space and one case (2.56%) of paravertebral leakage. Median survival
      time was extended to 13 months. CONCLUSION: The safety and efficacy of PVP
      combined with IMRT in patients with NSCLC with metastatic lesions at centrum
      vertebrae and the ability to prevent the diseased vertebrae from further
      deformation and tumor infiltration into the vertebral body were demonstrated. PVP
      combined with IMRT should be the optimal technique for treatment of vertebral
      compression pain resulting from spinal metastatic NSCLC.

PMID- 26316784
TI  - Current and emerging treatment options for hairy cell leukemia.
AB  - Hairy cell leukemia (HCL) is a lymphoproliferative B-cell disorder characterized
      by pancytopenia, splenomegaly, and characteristic cytoplasmic hairy projections.
      Precise diagnosis is essential in order to differentiate classic forms from HCL
      variants, such as the HCL-variant and VH4-34 molecular variant, which are more
      resistant to available treatments. The current standard of care is treatment with
      purine analogs (PAs), such as cladribine or pentostatin, which provide a high
      rate of long-lasting clinical remissions. Nevertheless, ~30%-40% of the patients
      relapse, and moreover, some of these are difficult-to-treat refractory cases. The
      use of the monoclonal antibody rituximab in combination with PA appears to
      produce even higher responses, and it is often employed to minimize or eliminate
      residual disease. Currently, research in the field of HCL is focused on
      identifying novel therapeutic targets and potential agents that are safe and can
      universally cure the disease. The discovery of the BRAF mutation and progress in
      understanding the biology of the disease has enabled the scientific community to
      explore new therapeutic targets. Ongoing clinical trials are assessing various
      treatment strategies such as the combination of PA and anti-CD20 monoclonal
      antibodies, recombinant immunotoxins targeting CD22, BRAF inhibitors, and B-cell
      receptor signal inhibitors. 

PMID- 26316786
TI  - Epothilones in epithelial ovarian, fallopian tube, or primary peritoneal cancer:
      a systematic review.
AB  - Ovarian cancer is the most lethal gynecologic malignancy; consequently, there is
      a need for effective therapies. Epothilones are microtubule-stabilizing agents
      that inhibit cell growth. Currently, patupilone and its four synthetic
      derivatives ixabepilone, BMS-310705, sagopilone, 20-desmethyl-20-methylsulfanyl
      epothilone B and epothilone D, as well as its derivative KOS-1584, are under
      clinical evaluation. This is the first systematic review conducted in accordance
      with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta
      Analyses) guidelines that synthesizes all available data emerging from trials and
      evaluates the efficacy and safety of epothilones in epithelial ovarian, primary
      fallopian tube, and primary peritoneal cancer. Despite the fact that epothilones
      have proven active in taxane-resistant settings in preclinical models, it is not
      yet clear from Phase II/III studies reviewed here that their clinical activity is
      superior to that of taxanes. Nevertheless, responses to epothilones have been
      observed in platinum-refractory/resistant ovarian cancer patients. Moreover,
      despite the shared mechanism of action of epothilones, their clinical profile
      seems clearly different, with diarrhea being the most common dose-limiting
      toxicity encountered with patupilone, whereas neutropenia and sensory neuropathy
      are the most common toxic effects observed with the other epothilones. In any
      case, randomized trials comparing epothilones with standard treatments seem
      warranted to define further the role of these agents, whereas biomarker analysis
      might further optimize patient selection. 

PMID- 26316787
TI  - A narrative review of cost-effectiveness analysis of people living with HIV
      treated with HAART: from interventions to outcomes.
AB  - BACKGROUND: Since its introduction in 1996, highly active antiretroviral therapy
      (HAART), which involves the combination of antiretroviral drugs, has resulted in
      significant improvements in the morbidity, mortality, and life expectancy of HIV
      infected patients. Numerous studies of the cost-effectiveness of HAART from
      different perspectives in HIV have been reported. AIM: To investigate the
      economic outcomes and relevance of HAART for people living with HIV. MATERIALS
      AND METHODS: A narrative literature review was conducted on 22 peer-reviewed full
      economic evaluations of people living with HIV treated with different HAART
      regimens and published in English between January 2005 and December 2014.
      Information regarding study details, such as interventions, outcomes, and
      modeling methods, was extracted. The high heterogeneity of the included studies
      rendered a meta-analysis inappropriate; therefore, we conducted a comparative
      analysis of studies grouped according to the similarity of the different
      intervention types and outcomes. RESULTS: Most of the economic evaluations of
      HAART focused on comparisons between the specific HAART regimens and others from
      the following perspectives: injecting drug users versus noninjecting drug users,
      HIV-infected adults without AIDS versus those with AIDS, regimens based on
      developed world guidelines versus those based on developing world guidelines,
      self-administered HAART versus directly observed HAART, and "ideal" versus
      "typical" regimens. CONCLUSION: In general, HAART is more cost-effective than
      other therapeutic regimens adopted so far. Further investigations, especially
      head-to-head comparisons of "ideal" and "typical" trials of different regimen
      combinations, are required to identify the optimal HAART regimens.

PMID- 26316788
TI  - A novel, long-acting glucagon-like peptide receptor-agonist: dulaglutide.
AB  - BACKGROUND: Dulaglutide is a new, long-acting glucagon-like peptide analogue in
      the treatment of type 2 diabetes. It is available in two doses, 0.75 and 1.5 mg,
      given by injection once weekly. This systematic review reports the effectiveness
      and safety of dulaglutide in type 2 diabetes in dual and triple therapy. METHODS:
      MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, and
      conference abstracts were searched from 2005 to August 2014, and updated in
      January 2015. Company websites and references of included studies were checked
      for potentially relevant studies. European Medicines Agency and US Food and Drug
      Administration websites were searched. RESULTS: Four trials were included. All
      were manufacturer-funded randomized controlled trials from the Assessment of
      Weekly Administration of Dulaglutide in Diabetes (AWARD) program. AWARD-1
      compared dulaglutide 1.5 mg against exenatide 10 ug twice daily and placebo,
      AWARD-2 compared dulaglutide 0.75 and 1.5 mg against insulin glargine, AWARD-5
      compared dulaglutide 0.75 and 1.5 mg against sitagliptin 100 mg and placebo, and
      AWARD-6 compared dulaglutide 1.5 mg against liraglutide 1.8 mg. The duration of
      follow-up in the trials ranged from 26 to 104 weeks. The primary outcome of all
      the included trials was change in HbA1c. At 26 weeks, greater HbA1c reductions
      were seen with dulaglutide than with twice daily exenatide (dulaglutide 1.5/0.75
      mg: -1.5%/-1.3%; exe: 0.99%) and sitagliptin (1.5/0.75 mg -1.22%/-1.01%;
      sitagliptin: -0.6%). HbA1c change was greater with dulaglutide 1.5 mg (-1.08%)
      than with glargine (-0.63%), but not with dulaglutide 0.75 mg (-0.76%).
      Dulaglutide 1.5 mg was found to be noninferior to liraglutide 1.8 mg. More
      patients treated with dulaglutide achieved HbA1c targets of <7% and <=6.5%.
      Reduction in weight was greater with dulaglutide than with sitagliptin and
      exenatide. Hypoglycemia was infrequent. The main adverse events were nausea,
      diarrhea, and vomiting. CONCLUSION: Dulaglutide is effective in the treatment of
      patients with type 2 diabetes but we need long follow-up data for safety
      concerns.

PMID- 26316785
TI  - Merkel cell carcinoma of the head and neck: pathogenesis, current and emerging
      treatment options.
AB  - Merkel cell carcinoma (MCC) is a relatively uncommon, neuroendocrine, cutaneous
      malignancy that often exhibits clinically aggressive features and is associated
      with a poor prognosis. It typically presents as a painless, rapidly enlarging,
      dome-shaped red or purplish nodule in a sun-exposed area of the head and neck or
      upper extremities. Our understanding of MCC has increased dramatically over the
      last several years and the pathogenesis continues to be an area of active
      research. The etiology is likely multifactorial with immunosuppression, UV
      induced skin damage, and viral factors contributing to the development of MCC.
      The recent discovery of Merkel cell polyomavirus has allowed for at least one
      aspect of disease development to be much better understood. In most cases,
      treatment consists of wide local excision with adjuvant radiation therapy. The
      role of chemotherapeutics is still being defined. The recent advancement of
      knowledge regarding the pathogenesis of MCC has led to an explosion research into
      novel therapeutic agents and strategies. This review seeks to summarize the
      current body of literature regarding the pathogenesis of MCC and potential
      targets for future therapies. 

PMID- 26316789
TI  - Lixisenatide accelerates restoration of normoglycemia and improves human beta
      cell function and survival in diabetic immunodeficient NOD-scid IL-2rg(null) RIP
      DTR mice engrafted with human islets.
AB  - OBJECTIVE: Glucagon-like peptide-1 induces glucose-dependent insulin secretion
      and, in rodents, increases proliferation and survival of pancreatic beta cells.
      To investigate the effects on human beta cells, we used immunodeficient mice
      transplanted with human islets. The goal was to determine whether lixisenatide, a
      glucagon-like peptide-1 receptor agonist, improves human islet function and
      survival in vivo. METHODS: Five independent transplant studies were conducted
      with human islets from five individual donors. Diabetic human islet-engrafted
      immunodeficient mice were treated with lixisenatide (50, 150, and 500 ug/kg) or
      vehicle. Islet function was determined by blood glucose, plasma human insulin/C
      peptide, and glucose tolerance tests. Grafts were analyzed for total beta- and
      alpha-cell number, percent proliferation, and levels of apoptosis. RESULTS:
      Diabetic mice transplanted with marginal human islet mass and treated with
      lixisenatide were restored to euglycemia more rapidly than vehicle-treated mice.
      Glucose tolerance tests, human plasma insulin, and glucose-stimulation indices of
      lixisenatide-treated mice were significantly improved compared to vehicle-treated
      mice. The percentages of proliferating or apoptotic beta cells at graft recovery
      were not different between lixisenatide-treated and vehicle-treated mice.
      Nevertheless, in one experiment we found a significant twofold to threefold
      increase in human beta-cell numbers in lixisenatide-treated compared to vehicle
      treated mice. CONCLUSION: Diabetic human islet-engrafted immunodeficient mice
      treated with lixisenatide show improved restoration of normoglycemia, human
      plasma insulin, and glucose tolerance compared to vehicle-treated mice engrafted
      with the same donor islets. Because the proliferative capacity of human beta
      cells is limited, improved beta-cell survival coupled with enhanced beta-cell
      function following lixisenatide treatment may provide the greatest benefit for
      diabetic patients with reduced functional islet mass.

PMID- 26316790
TI  - Study of lipid profile in adult women with acne.
AB  - OBJECTIVE: The aim of this study was to establish the lipid profile of female
      patients with acne in the Acne-in-Adult-Women Ambulatory Care Clinic in order to
      observe the prevalence of dyslipidemia in those patients. METHODS: This is a
      retrospective transversal study that evaluated the medical records of 416
      patients who attended at the Acne-in-Adult-Women Ambulatory Care Clinic, at the
      Dermatology Department, Faculdade de Medicina do ABC, Santo Andre, Sao Paulo,
      Brazil, in the year 2012. Relevant data included age and clinical classification
      of acne. The lipid profile was analyzed according to the results of laboratory
      tests ordered during outpatient visits, which included total and fractionated
      cholesterol levels and triglycerides. RESULTS: The epidemiological study sample
      was of 219 patients, with ages ranging from 21 to 61 years (mean of 32.23 years).
      The predominant clinical grade was papule-pustule acne (grade II) with 156
      patients (71%). Regarding the lipid profile of the patients, there was a high
      increase in total cholesterol levels in 17.35% of the cases. High-density
      lipoprotein levels were low in 11.42% of the patients, with normal prevalence in
      194 subjects. Low-density lipoprotein levels were normal in most patients
      (60.27%). Very-low-density lipoprotein values were normal in almost all patients
      (94.06%) and increased in only 13 patients (5.94%). Only 18 patients presented
      high levels of triglycerides (8.22%). CONCLUSION: The conclusion was that
      patients with grades II and III acne are more likely to have total cholesterol
      and low-density lipoprotein altered. A correct and early diagnosis can be an
      important measure for the prevention of the metabolic syndrome in these patients.

PMID- 26316791
TI  - Saccharomyces boulardii CNCM I-745 supports regeneration of the intestinal
      microbiota after diarrheic dysbiosis - a review.
AB  - The probiotic medicinal yeast Saccharomyces cerevisiae HANSEN CBS 5926
      (Saccharomyces boulardii CNCM I-745) is used for the prevention and treatment of
      diarrhea. Its action is based on multiple mechanisms, including immunological
      effects, pathogen-binding and antitoxinic effects, as well as effects on
      digestive enzymes. Correlated with these effects, but also due to its inherent
      properties, S. boulardii is able to create a favorable growth environment for the
      beneficial intestinal microbiota, while constituting extra protection to the host
      mucus layer and mucosa. This review focuses on the positive influence of S.
      boulardii on the composition of the intestinal microbiota. In a dysbiosis, as
      during diarrhea, the main microbial population (especially Lachnospiraceae,
      Ruminococcaceae, Bacteroidaceae, and Prevotellaceae) is known to collapse by at
      least one order of magnitude. This gap generally leads to transient increases in
      pioneer-type bacteria (Enterobacteriaceae, Bifidobacteriaceae, and
      Clostridiaceae). Several human studies as well as animal models demonstrate that
      treatment with S. boulardii in dysbiosis leads to the faster reestablishment of a
      healthy microbiome. The most relevant effects of S. boulardii on the fecal
      composition include an increase of short chain fatty acid-producing bacteria
      (along with a rise in short chain fatty acids), especially of Lachnospiraceae and
      Ruminococcaceae, as well as an increase in Bacteroidaceae and Prevotellaceae. At
      the same time, there is a suppression of pioneer bacteria. The previously
      observed preventive action of S. boulardii, eg, during antibiotic therapy or
      regarding traveler's diarrhea, can be explained by several mechanisms, including
      a stabilizing effect on the healthy microbiota as well as possibly on the mucus
      layer. Several different dysbiotic situations could profit from the effects of S.
      boulardii CNCM I-745. Its additional potential lies in a general stabilization of
      the gut flora for at-risk populations. More studies are needed to explore the
      full potential of this versatile probiotic yeast. 

PMID- 26316792
TI  - Pharmacologic therapy for inflammatory bowel disease refractory to steroids.
AB  - Although corticosteroids are an effective treatment for induction of remission in
      inflammatory bowel disease (IBD), many patients are dependent on or refractory to
      corticosteroids. This review is based on scrutinizing current literature with
      emphasis on randomized controlled trials, meta-analyses, and Cochrane reviews on
      the management of IBD refractory to corticosteroids. Based on this evidence, we
      propose algorithms and optimization strategies for use of immunomodulator and
      biologic therapy in IBD refractory to corticosteroids. 

PMID- 26316794
TI  - An ex vivo RT-qPCR-based assay for human peripheral leukocyte responsiveness to
      glucocorticoids in surgically induced inflammation.
AB  - INTRODUCTION: An assay to determine glucocorticoid (GC) responsiveness in humans
      could be used to monitor GC non-responsiveness in states of GC insufficiency and
      could provide a tool to adapt GC treatment to individual patients. We propose an
      ex vivo assay to test GC responsiveness in peripheral leukocytes. The assay was
      evaluated in a human experimental model of surgery-induced inflammation. PATIENTS
      AND METHODS: Changes in expression of the GC-regulated genes GILZ, IL1R2, FKBP5,
      and HLA-DR and glucocorticoid receptor alpha (GRalpha) were determined by reverse
      transcriptase quantitative polymerase chain reaction (RT-qPCR) in peripheral
      leukocytes from surgical patients and healthy blood donors (total n=60) in
      response to low (1 nM) and high (1 uM) dexamethasone (DEX). The final selection
      of a suitable endogenous control gene was based on the studies of stability
      during DEX treatment and inflammation. Correlations between pre- and
      postoperative GC-induced gene expression, the postoperative systemic inflammatory
      and metabolic response (CRP, IL-6, white blood cell count, cytokines, resistin,
      free fatty acids, glucose, insulin, and adiponectin), and the clinical outcome
      were analyzed. The length of stay in the intensive care unit (ICU-LOS), the
      length of stay in the hospital, and postoperative complications were used to
      measure clinical outcome. RESULTS: When the blood donors were compared to the
      patients, there were no significant differences in the regulation of the genes in
      response to DEX, except for GRalpha. Preoperative, but not postoperative, gene
      regulation of GILZ and GRalpha was negatively correlated to ICU-LOS (P<0.05 and
      P<0.01, respectively). Preoperative GILZ and FKBP5 gene regulation was negatively
      correlated to postoperative systemic TNFalpha and MIP-1alpha levels. CONCLUSION:
      We suggest that this assay could be used to determine GC responsiveness. An
      alteration in preoperative GC responsiveness may be related to a patient's
      ability to recover from surgically induced inflammatory stress.

PMID- 26316793
TI  - Differential inflammatory response to Helicobacter pylori infection: etiology and
      clinical outcomes.
AB  - The bacterial pathogen Helicobacter pylori commonly colonizes the human gastric
      mucosa during early childhood and persists throughout life. The organism has
      evolved multiple mechanisms for evading clearance by the immune system and,
      despite inducing inflammation in the stomach, the majority of infections are
      asymptomatic. H. pylori is the leading cause of peptic ulcer disease and gastric
      cancer. However, disease outcomes are related to the pattern and severity of
      chronic inflammation in the gastric mucosa, which in turn is influenced by both
      bacterial and host factors. Despite over 2 decades of intensive research, there
      remains an incomplete understanding of the circumstances leading to disease
      development, due to the fascinating complexity of the host-pathogen interactions.
      There is accumulating data concerning the virulence factors associated with
      increased risk of disease, and the majority of these have pro-inflammatory
      activities. Despite this, only a small proportion of those infected with virulent
      strains develop disease. Several H. pylori virulence factors have multiple
      effects on different cell types, including the induction of pro- and anti
      inflammatory, immune stimulatory, and immune modulatory responses. The expression
      of multiple virulence factors is also often linked, making it difficult to assess
      the meaning of their effects in isolation. Overall, H. pylori is thought to
      usually modulate inflammation and limit acute damage to the mucosa, enabling the
      bacteria to persist. If this delicate balance is disturbed, disease may then
      develop. 

PMID- 26316796
TI  - C-reactive protein levels in combination with abdominal CT scans is a useful tool
      to predict the macroscopic appearance in late-stage EPS patients prior to
      surgery.
AB  - BACKGROUND: Diagnosis of encapsulating peritoneal sclerosis (EPS) is based on
      clinical symptoms, radiologic findings, and macroscopic or histological criteria.
      Two diagnostic scores for radiologic findings in computed tomography (CT) scans
      of patients with EPS have been established in the past (by Tarzi et al and Vlijm
      et al). The macroscopic appearance of EPS has previously been separated into
      three types. The use of CT scan as a tool to predict different macroscopic
      phenotypes, leading to specific surgical techniques and different medical
      treatment, has not yet been investigated. METHODS: We retrospectively analyzed 30
      patients with late-stage EPS who underwent major surgery with peritonectomy and
      enterolysis. The preoperative CT scans were scored according to the two
      aforementioned established diagnostic CT scores. The macroscopic phenotype,
      surgical procedure, and laboratory values at the time of surgery were evaluated.
      CT findings in the different macroscopic phenotypes were analyzed. RESULTS: All
      patients had highly predictive CT scores for EPS. The macroscopic Type III had
      significantly higher CT scores compared with the other macroscopic phenotypes.
      Patients with macroscopic Type I had significantly higher C-reactive protein
      values compared to EPS Type III. Operation time was significantly longer, and
      repeated surgery and intraoperative complications were more frequent in EPS Type
      I compared with EPS Type III (P<0.05). Using the CT score and CRP level, the
      sensitivities for prediction of EPS I and III were 78% and 87% with corresponding
      specificities of 67% and 93%. CONCLUSION: Abdominal CT scans might help to
      identify patients with a higher risk of complications and provide important
      information for the surgical intervention prior to surgery.

PMID- 26316795
TI  - Inflammatory etiopathogenesis of systemic lupus erythematosus: an update.
AB  - The immune system struggles every day between responding to foreign antigens and
      tolerating self-antigens to delicately maintain tissue homeostasis. If self
      tolerance is broken, the development of autoimmunity can be the consequence, as
      it is in the case of the chronic inflammatory autoimmune disease systemic lupus
      erythematosus (SLE). SLE is considered to be a multifactorial disease comprising
      various processes and cell types that act abnormally and in a harmful way.
      Oxidative stress, infections, or, in general, tissue injury are accompanied by
      massive cellular demise. Several processes such as apoptosis, necrosis, or
      NETosis (formation of Neutrophil Extracellular Traps [NETs]) may occur alone or
      in combination. If clearance of dead cells is insufficient, cellular debris may
      accumulate and trigger inflammation and leakage of cytoplasmic and nuclear
      autoantigens like ribonucleoproteins, DNA, or histones. Inadequate removal of
      cellular remnants in the germinal centers of secondary lymphoid organs may result
      in the presentation of autoantigens by follicular dendritic cells to autoreactive
      B cells that had been generated by chance during the process of somatic
      hypermutation (loss of peripheral tolerance). The improper exposure of nuclear
      autoantigens in this delicate location is consequently prone to break self
      tolerance to nuclear autoantigens. Indeed, the germline variants of
      autoantibodies often do not show autoreactivity. The subsequent production of
      autoantibodies plays a critical role in the development of the complex
      immunological disorder fostering SLE. Immune complexes composed of cell-derived
      autoantigens and autoantibodies are formed and get deposited in various tissues,
      such as the kidney, leading to severe organ damage. Alternatively, they may also
      be formed in situ by binding to planted antigens of circulating autoantibodies.
      Here, we review current knowledge about the etiopathogenesis of SLE including the
      involvement of different types of cell death, serving as the potential source of
      autoantigens, and impaired clearance of cell remnants, causing accumulation of
      cellular debris. 

PMID- 26316797
TI  - Elevation of urinary liver-type fatty acid binding protein after cardiac
      catheterization related to cardiovascular events.
AB  - PURPOSE: Contrast medium (CM) induces tubular hypoxia via endothelial damage due
      to direct cytotoxicity or viscosity. Urinary liver-type fatty acid binding
      protein (L-FABP) increases along with tubular hypoxia and may be a detector of
      systemic circulation injury. The aim of this study was to evaluate the clinical
      usefulness of detecting increases in urinary L-FABP levels due to administration
      of CM, as a prognostic biomarker for cardiovascular disease in patients without
      occurrence of CM-induced nephropathy undergoing cardiac catheterization procedure
      (CCP). METHODS: Retrospective longitudinal analyses of the relationship between
      urinary L-FABP levels and occurrence of cardiovascular events were performed
      (n=29). Urinary L-FABP was measured by ELISA before CCP, and at 6, 12, 24, and 48
      hours after CCP. RESULTS: Urinary L-FABP levels were significantly higher at 12
      hours (P<0.05) and 24 hours (P<0.005) after CCP compared with before CCP, only in
      the patients with occurrence of cardiovascular events (n=17), but not in those
      without cardiovascular events (n=12). The parameter with the largest area under
      the curve (0.816) for predicting the occurrence of cardiovascular events was the
      change in urinary L-FABP at 24 hours after CCP. The difference in urinary L-FABP
      levels (DeltaL-FABP >=11.0 MUg/g creatinine) between before CCP and at 24 hours
      after CCP was a risk factor for the occurrence of cardiovascular events (hazard
      ratio, 4.93; 95% confidence interval, 1.27-19.13; P=0.021). CONCLUSION:
      Measurement of urinary L-FABP before CCP and at 24 hours after CCP in patients
      with mild to moderate renal dysfunction may be an important indicator for risk
      stratification of onset of cardiovascular events.

PMID- 26316798
TI  - Is stoma care effective in terms of morbidity in complicated ileostomies?
AB  - BACKGROUND: Performing transient or permanent ileostomy is one of the common
      procedures involved in colorectal surgery. Complication rates up to 40% have been
      reported in ileostomies. In this report, the effect of specific stoma care unit
      on ileostomy and its complications were investigated. METHODS: A total of 141
      patients, who were operated and underwent ileostomy, due to different causes, at
      Department of General Surgery, Uludag University, Bursa, Turkey, between 2003 and
      2006, were examined, retrospectively. Patient records were examined in terms of
      age, sex, surgery indications, urgent/elective state, benign/malign origin,
      ileostomy type, complications and stoma care, and education. chi(2) test was used
      to compare the categorical data. RESULTS: Among the patients, 95 (67%) were male
      and 46 (33%) were female. The mean age was 47 years (17-67). Some of the subjects
      (49%) were operated urgently and some (51%) were under elective conditions. The
      ileostomy types used included the following: end ileostomy (43%), loop ileostomy
      (46%), and double-barrel ileostomy (11%). Permanent ileostomy was performed in 23
      patients and transient ileostomy was performed in 118 patients. The patients were
      operated because of either benign (48%) or malign (52%) causes. Complications
      developed in 37 (26%) patients. The rate of development of complication was
      markedly higher in ileostomies performed under urgent conditions (61% vs 39%)
      (P<0.001). The complications included mucocutaneous separation (12 patients),
      maceration in the peristomal skin (ten patients), retraction (five patients),
      necrosis (three patients), prolapsus (three patients), and other metabolic
      complications (four patients). The complications were treated with care (68%) and
      surgical revision (32%). CONCLUSION: The rate of ileostomy was found to be higher
      in the male patients compared to female patients. The risk of development of
      complications was found to be higher in ileostomies performed under urgent
      conditions. The most common complication observed was mucocutaneous separation.
      Ileostomy complications can be treated conservatively with professional care and
      education.

PMID- 26316799
TI  - Health behaviors and quality of life predictors for risk of hospitalization in an
      electronic health record-linked biobank.
AB  - BACKGROUND: Hospital risk stratification models using electronic health records
      (EHRs) often use age and comorbid health burden. Our primary aim was to determine
      if quality of life or health behaviors captured in an EHR-linked biobank can
      predict future risk of hospitalization. METHODS: Participants in the Mayo Clinic
      Biobank completed self-administered questionnaires at enrollment that included
      quality of life and health behaviors. Participants enrolled as of December 31,
      2010 were followed for one year to ascertain hospitalization. Data on
      comorbidities and hospitalization were derived from the Mayo Clinic EHR. Hazard
      ratios (HR) and 95% confidence interval (CI) were used, adjusted for age and sex.
      We used gradient boosting machines models to integrate multiple factors.
      Different models were compared using C-statistic. RESULTS: Of the 8,927 eligible
      Mayo Clinic Biobank participants, 834 (9.3%) were hospitalized. Self-perceived
      health status and alcohol use had the strongest associations with risk of
      hospitalization. Compared to participants with excellent self-perceived health,
      those reporting poor/fair health had higher risk of hospitalization (HR =3.66,
      95% CI 2.74-4.88). Alcohol use was inversely associated with hospitalization (HR
      =0.57 95% CI 0.45-0.72). The gradient boosting machines model estimated self
      perceived health as the most influential factor (relative influence =16%). The
      predictive ability of the model based on comorbidities was slightly higher than
      the one based on the self-perceived health (C-statistic =0.67 vs 0.65).
      CONCLUSION: This study demonstrates that self-perceived health may be an
      important piece of information to add to the EHR. It may be another method to
      determine hospitalization risk.

PMID- 26316800
TI  - Acute metabolic response to fasted and postprandial exercise.
AB  - The aim of this study was to analyze the acute metabolic response to exercise in
      fasting and postprandial. For this, ten individuals were submitted to an
      incremental treadmill test, with an initial speed of 5 and 1 km/h increments
      every minute, with no inclination, and a body composition assessment. After this
      1st day, all volunteers were submitted to two experimental procedures (fasting
      and postprandial), with an aerobic exercise performed for 36 minutes at 65% of
      maximal oxygen consumption. At postprandial procedure, all subjects ingested a
      breakfast containing 59.3 g of carbohydrate (76.73%), 9.97 g of protein (12.90%),
      8.01 g of lipids (10.37%), with a total energy intake of 349.17 kcal. An analysis
      of plasma concentration of triglycerides, lactate, and glucose was performed in
      two stages: before and after exercise. The Shapiro-Wilk test was used to verify
      the normality of the data. For analysis of glucose concentration, plasma lactate,
      and triglycerides, we used a repeated measures analysis of variance factorial
      2*2, with Bonferroni multiple comparison test. The significance level of P<0.05
      was adopted. The results indicated a maintenance level of glucose at fasting and
      a decrease in glucose concentration at postprandial exercise. Both conditions
      increase plasma lactate. Triglycerides also increased in the two experimental
      conditions; however, after exercise fasting, the increase was significantly
      higher than in the postprandial exercise. These data suggest that both exercises
      could increase plasma lactate and triglycerides. However, exercise performed in
      fasting condition decreases glucose concentration and increases triglycerides,
      even more than postprandial exercise. 

PMID- 26316802
TI  - Effects of context and individual predispositions on hypervigilance to pain-cues:
      an ERP study.
AB  - BACKGROUND: Hypervigilance to pain is the automatic prioritization of pain
      related compared with other stimuli. The processing of threat information is
      influenced by negative contexts. Therefore, we intended to explore such context
      effects on hypervigilance to pain-cues, taking individual differences in self
      reported vigilance to pain into consideration. METHODS: In all, 110 healthy
      subjects viewed task-irrelevant emotional facial expressions (anger, happy,
      neutral, and pain) overlaid in half of the trials with a fine grid. The
      instructed task was to indicate the presence/absence of this grid. A threatening
      context was established by applying electrical stimuli slightly below pain
      threshold. Using scores of Pain Vigilance and Awareness Questionnaire, the sample
      was divided into high vs low pain vigilant subjects. Reaction times and event
      related brain potentials were recorded. RESULTS: No distinct attentional
      processing of pain faces (based on the event-related brain potentials) was
      observed as a function of high levels of self-reported vigilance to pain and
      contextual threat induction. High pain vigilant subjects showed generally
      enhanced processing of emotional and neutral faces as indicated by parameters of
      early (early posterior negativity) and late (late positive complex) processing
      stages. This enhancement was abolished when electro-stimuli were presented.
      CONCLUSION: Contextual threat does not enhance the attentional capture of pain
      cues when they are presented concurrently with competing task demands. The study
      could, however, replicate a generally enhanced attentional processing of
      emotional cues in high pain vigilant subjects. This underpins that hypervigilance
      to pain is related to changes in emotional processing.

PMID- 26316801
TI  - Physical symptoms in outpatients with psychiatric disorders consulting the
      general internal medicine division at a Japanese university hospital.
AB  - PURPOSE: General practitioners have an important role in diagnosing a variety of
      patients, including psychiatric patients with complicated symptoms. We evaluated
      the relationship between physical symptoms and psychiatric disorders in general
      internal medicine (GIM) outpatients in a Japanese university hospital. MATERIALS
      AND METHODS: We coded the symptoms and diagnoses of outpatients from medical
      documents using the International Classification of Primary Care, second edition
      (ICPC-2). The participants were new outpatients who consulted the GIM outpatient
      division at Jichi Medical University Hospital in Tochigi, Japan from January
      June, 2012. We reviewed all medical documents and noted symptoms and diagnoses.
      These were coded using ICPC-2. RESULTS: A total of 1,194 participants were
      evaluated, 148 (12.4%) of whom were diagnosed as having psychiatric disorders.
      The prevalence of depression, anxiety disorder, and somatization was 19.6%
      (number [n] =29), 14.9% (n=22), and 14.2% (n=21), respectively, among the
      participants with psychiatric disorders. The presence of several particular
      symptoms was associated with having a psychiatric disorder as compared with the
      absence of these symptoms after adjusting for sex, age, and the presence of
      multiple symptoms (odds ratio [OR] =4.98 [95% confidence interval {CI}: 1.66
      14.89] for palpitation; OR =4.36 [95% CI: 2.05-9.39] for dyspnea; OR =3.46 [95%
      CI: 1.43-8.36] for tiredness; and OR =2.99 [95% CI: 1.75-5.13] for headache).
      CONCLUSION: Not only the psychiatric symptoms, but also some physical symptoms,
      were associated with psychiatric disorders in GIM outpatients at our university
      hospital. These results may be of help to general practitioners in appropriately
      approaching and managing patients with psychiatric disorders.

PMID- 26316803
TI  - Patterns of health care utilization for low back pain.
AB  - BACKGROUND: The purpose of this study was to determine if primary care patients
      with low back pain (LBP) cluster into definable care utilization subgroups that
      can be explained by patient and provider characteristics. MATERIALS AND METHODS:
      Adult primary care patients with an incident LBP encounter were identified from
      Geisinger Clinic electronic health records over 5 years. Two-thirds of the cohort
      had only one to two encounters. Principal component analysis was applied to the
      data from the remaining one-third on use of ambulatory, inpatient, emergency
      department, and surgery care and use of magnetic resonance imaging, injections,
      and opioids in 12 months following the incident encounter. Groups were compared
      on demographics, health behaviors, chronic and symptomatic disease burden, and a
      measure of physician efficiency. RESULTS: Six factors with eigenvalues >1.5
      explained 71% of the utilization variance. Patient subgroups were defined as: 1-2
      LBP encounters; 2+ surgeries; one surgery; specialty care without primary care;
      3+ opioid prescriptions; laboratory dominant care; and others. The surgery and 3+
      opioid subgroups, while accounting for only 10.4% of the cohort, had used
      disproportionately more magnetic resonance imaging, emergency department,
      inpatient, and injectable resources. The specialty care subgroup was
      characterized by heavy use of inpatient care and the lowest use of injectables.
      Anxiety disorder and depression were not more prevalent among the surgery
      patients than in the others. Surgery patients had features in common with
      specialty care patients, but were older, had higher prevalence of Fibromyalgia,
      and were associated primary care physicians with worse efficiency scores.
      CONCLUSION: LBP care utilization is highly variable and concentrated in small
      subgroups using disproportionate amounts of potentially avoidable care that
      reflect both patient and provider characteristics.

PMID- 26316804
TI  - Migraine: treatments, comorbidities, and quality of life, in the USA.
AB  - This study sought to characterize the experience of stress, treatment patterns,
      and medical and disability profile in the migraineur population to better
      understand how the experience of migraines impacts the social and psychological
      functioning of this group. A 30-minute self-report survey was presented via a
      migraine-specific website with data collection occurring between May 15 and June
      15, 2012. Recruitment for the study was done through online advertisements. In
      total, 2,907 individuals began the survey and 2,735 met the inclusion criteria
      for the study. The sample was predominantly female (92.8%). Migraine-associated
      stress was correlated with length of time since first onset of symptoms (P<0.01)
      and number of symptoms per month (P<0.01). Disorders related to stress, such as
      depression (P<0.01) and anxiety (P<0.01), were also positively correlated with
      the measured stress resulting from migraines. Migraine-associated stress must be
      understood as a multidimensional experience with broader impacts of stress on an
      individual correlating much more highly with negative mental and physical health
      profiles. Stress resulting from frequent migraine headaches may contribute to the
      development of medical and psychological comorbidities and may be a part of a
      cyclical relationship wherein stress is both a cause and effect of the social and
      medical impairments brought about by migraine. 

PMID- 26316805
TI  - Mucosal versus muscle pain sensitivity in provoked vestibulodynia.
AB  - BACKGROUND: An estimated 8.3%-16% of women experience vulvovaginal discomfort
      during their lifetime. Frequently these patients report provoked pain on contact
      or with attempted intercourse, commonly referred to as provoked vestibulodynia
      (PVD). Despite the burden of this condition, little is known about its potential
      etiologies including pelvic floor muscular dysfunction and mucosal components.
      This knowledge would be beneficial in developing targeted therapies including
      physical therapy. OBJECTIVE: To explore the relative contribution of mucosal
      versus muscle pain sensitivity on pain report from intercourse among women with
      PVD. DESIGN: In this proof of concept study, 54 women with PVD underwent a
      structured examination assessing mucosal and pelvic muscle sensitivity. METHODS:
      We examined three mucosal sites in the upper and lower vestibule. Patients were
      asked to rate their pain on cotton swab palpation of the mucosa using a 10-point
      visual analog scale. Muscle pain was assessed using transvaginal application of
      pressure on right and left puborectalis, and the perineal muscle complex. The
      Gracely pain scale (0-100) was used to assess the severity of pain with
      intercourse, with women rating the lowest, average, and highest pain levels; a
      100 rating the highest level of pain. RESULTS: The lower vestibule's mucosa 5.81
      (standard deviation =2.83) was significantly more sensitive than the upper
      vestibule 2.52 (standard deviation =2.6) (P<0.01) on exam. However, mucosal
      sensitivity was not associated with intercourse pain, while muscle sensitivity
      was moderately associated with both average and highest intensity of intercourse
      pain (r=-0.46, P=0.01 and r=-0.42, P=0.02), respectively. CONCLUSION: This
      preliminary study suggests that mucosal measures alone may not sufficiently
      capture the spectrum of clinical pain report in women with PVD, which is
      consistent with the empirical success of physical therapy in this population.

PMID- 26316806
TI  - Spinal cord stimulation for treatment of the pain associated with hereditary
      multiple osteochondromas.
AB  - OBJECTIVE: Hereditary multiple osteochondromas (HMO) usually presents with
      neoplastic lesions throughout the skeletal system. These lesions frequently cause
      chronic pain and are conventionally treated with surgical resection and
      medication. In cases where conventional treatments have failed, spinal cord
      stimulation (SCS) could be considered as a potential option for pain relief. The
      objective of this case was to determine if SCS may have a role in treating pain
      secondary to neoplastic lesions from HMO. CASE PRESENTATION: We report a 65-year
      old female who previously received both surgical and pharmacological
      interventions for treating HMO neoplastic pain in the lumbar, pelvis, femur, and
      tibial regions. These interventions either failed to offer significant pain
      relief or caused excessive lethargy. A SCS trial was then offered with a dual 16
      contact lead trial leading to 70%-80% improvement in pain from baseline and 85%
      reduction in oxycodone IR intake. This was followed by permanent implantation of
      two 2*8 contact paddle leads (T7-T8 and T9-T10 interspaces). After 8-week follow
      up, settings were further optimized resulting in an additional 30% improvement in
      pain compared to last visit. At 6-month follow-up, the patient reported continued
      pain relief. CONCLUSION: This case demonstrates the first successful use of SCS
      to treat both HMO and nonmalignant neoplastic-related pain. The patient reported
      pain improvement from baseline, reduced pain medication requirements, and
      subjective improvement in quality of life. Additionally, this case demonstrates
      the potential advantage of trialing multiple painful areas with a 16-contact lead
      in order to avoid multiple trials and placement.

PMID- 26316807
TI  - Assessing the prevalence of autoimmune, endocrine, gynecologic, and psychiatric
      comorbidities in an ethnically diverse cohort of female fibromyalgia patients:
      does the time from hysterectomy provide a clue?
AB  - BACKGROUND: This retrospective chart review investigated differences in the
      prevalence of medical comorbidity between women with fibromyalgia (FM) (n=219)
      and a control group women with chronic pain (CP) without FM (n=116). The specific
      aims were to compare the prevalence of autoimmune, psychiatric, endocrine,
      gynecologic pathology, the relationship between timing of gynecologic surgery,
      and pain onset. We additionally sought to compare the number of comorbidities in
      an ethnically diverse cohort. METHODS: This was a retrospective chart review of
      patients seen in FM or CP clinics at an academic medical center in 2009-2010.
      RESULTS: Logistic regression modeling found that gynecologic, endocrine, and
      autoimmune diagnoses were independently associated with a diagnosis of FM.
      Detailed analyses showed that thyroid disease (P<0.01) and gynecologic surgery
      (P<0.05) were significantly more common in FM. Women with FM were more likely to
      have multiple autoimmune, endocrine, gynecologic, or psychiatric pathologies. A
      relationship was observed between the timing of gynecologic surgery and pain
      onset in FM, with more surgeries observed in the years just prior to pain onset
      or in the year after pain onset. A similar pattern was not found in the control
      group. CONCLUSION: This study demonstrates that autoimmune, endocrine, and
      gynecologic pathologies occur more commonly in women with FM than in those with
      CP, which is consistent with findings in less ethnically diverse samples.
      Moreover, a relationship was found between timing of pain onset and gynecologic
      surgery. A larger prospective study of the relationship between gynecologic
      surgery and pain onset in FM is warranted.

PMID- 26316808
TI  - Skin impedance is not a factor in transcutaneous electrical nerve stimulation
      effectiveness.
AB  - OBJECTIVE: Transcutaneous electrical nerve stimulation (TENS) is a
      nonpharmacological intervention used to manage pain using skin surface
      electrodes. Optimal electrode placement is unclear. We hypothesized that better
      analgesia would occur if electrodes were placed over sites with lower skin
      impedance. Optimal site selection (OSS) and sham site selection (SSS) electrode
      sites on the forearm were identified using a standard clinical technique.
      METHODS: Experiment 1 measured skin impedance in the forearm at OSS and SSS.
      Experiment 2 was a crossover design double-blind randomized controlled trial
      comparing OSS-TENS, SSS-TENS, and placebo TENS (P-TENS) to confirm differences in
      skin impedance between OSS and SSS, and measure change in pressure pain threshold
      (PPT) following a 30-minute TENS treatment. Healthy volunteers were recruited
      (ten for Experiment 1 [five male, five female] and 24 for Experiment 2 [12 male,
      12 female]). TENS was applied for 30 minutes at 100 Hz frequency, 100 us pulse
      duration, and "strong but nonpainful" amplitude. RESULTS: Experiment 1 results
      demonstrate significantly higher impedance at SSS (17.69+/-1.24 Omega) compared
      to OSS (13.53+/-0.57 Omega) (P=0.007). For Experiment 2, electrode site impedance
      was significantly higher over SSS, with both the impedance meter (P=0.001) and
      the TENS unit (P=0.012) compared to OSS. PPT change was significantly greater for
      both OSS-TENS (P=0.024) and SSS-TENS (P=0.025) when compared to P-TENS. PPT did
      not differ between the two active TENS treatments (P=0.81). CONCLUSION: Skin
      impedance is lower at sites characterized as optimal using the described
      technique of electrode site selection. When TENS is applied at adequate
      intensities, skin impedance is not a factor in attainment of hypoalgesia of the
      forearm in healthy subjects. Further investigation should include testing in
      patients presenting with painful conditions.

PMID- 26316809
TI  - Effects of a pain self-management intervention combining written and video
      elements on health-related quality of life among people with different levels of
      education.
AB  - Combining written and video material could increase the impact of health
      education for people with less education, but more evidence is needed about the
      impact of combined materials in different formats, especially in the context of
      chronic pain self-management. This study tested the impact of combining written
      information about self-managing chronic joint pain, which used language at a high
      reading level, with a DVD containing narrative video material presented directly
      by patients, using language at a lower reading level. Physical and mental health
      related quality of life (36-Item Short Form Health Survey) was measured among 107
      men with hemophilia before and 6 months after being randomly assigned to receive
      an information booklet alone or the booklet plus the DVD. Analysis of covariance
      was used to compare health outcomes between randomized groups at follow-up, using
      the baseline measures as covariates, with stratified analyses for groups with
      different levels of education. The DVD significantly improved mental health
      related quality of life among those with only high school education. Video
      material could therefore supplement written information to increase its impact on
      groups with less education, and combined interventions of this type could help to
      achieve health benefits for disadvantaged groups who are most in need of
      intervention. 

PMID- 26316811
TI  - Comparison between treadmill and bicycle ergometer exercise tests in mild-to
      moderate hypertensive Nigerians.
AB  - BACKGROUND: Comparative cardiovascular responses to treadmill and bicycle
      ergometer (bike) exercise tests in hypertensive Nigerians are not known. This
      study compared cardiovascular responses to the two modes of exercise testing in
      hypertensives using maximal exercise protocols. METHODS: One hundred and ten male
      subjects with mild-to-moderate hypertension underwent maximal treadmill and bike
      test one after the other at a single visit in a simple random manner. Paired
      sampled t-test was used to compare responses to both exercise tests while chi
      squared test was used to compare categorical variables. RESULTS: The maximal
      heart rate (P<0.001), peak systolic blood pressure (P=0.02), rate pressure
      product (P<0.001), peak oxygen uptake (P<0.001), and exercise capacity (P<0.001)
      in metabolic equivalents were signifcantly higher on the treadmill than on the
      bike. CONCLUSION: Higher cardiovascular responses on treadmill in Nigerian male
      hypertensives in this study, similar to findings in non-hypertensives and non
      Nigerians in earlier studies, suggest that treadmill may be of better diagnostic
      utility in our population.

PMID- 26316810
TI  - Chronic pain in hypermobility syndrome and Ehlers-Danlos syndrome (hypermobility
      type): it is a challenge.
AB  - Generalized joint hypermobility (GJH) is highly prevalent among patients
      diagnosed with chronic pain. When GJH is accompanied by pain in >=4 joints over a
      period >=3 months in the absence of other conditions that cause chronic pain, the
      hypermobility syndrome (HMS) may be diagnosed. In addition, GJH is also a
      clinical sign that is frequently present in hereditary diseases of the connective
      tissue, such as the Marfan syndrome, osteogenesis imperfecta, and the Ehlers
      Danlos syndrome. However, within the Ehlers-Danlos spectrum, a similar
      subcategory of patients having similar clinical features as HMS but lacking a
      specific genetic profile was identified: Ehlers-Danlos syndrome hypermobility
      type (EDS-HT). Researchers and clinicians have struggled for decades with the
      highly diverse clinical presentation within the HMS and EDS-HT phenotypes
      (Challenge 1) and the lack of understanding of the pathological mechanisms that
      underlie the development of pain and its persistence (Challenge 2). In addition,
      within the HMS/EDS-HT phenotype, there is a high prevalence of psychosocial
      factors, which again presents a difficult issue that needs to be addressed
      (Challenge 3). Despite recent scientific advances, many obstacles for clinical
      care and research still remain. To gain further insight into the phenotype of
      HMS/EDS-HT and its mechanisms, clearer descriptions of these populations should
      be made available. Future research and clinical care should revise and create
      consensus on the diagnostic criteria for HMS/EDS-HT (Solution 1), account for
      clinical heterogeneity by the classification of subtypes within the HMS/EDS-HT
      spectrum (Solution 2), and create a clinical core set (Solution 3). 

PMID- 26316812
TI  - Simulation in teaching regional anesthesia: current perspectives.
AB  - The emerging subspecialty of regional anesthesiology and acute pain medicine
      represents an opportunity to evaluate critically the current methods of teaching
      regional anesthesia techniques and the practice of acute pain medicine. To date,
      there have been a wide variety of simulation applications in this field, and
      efficacy has largely been assumed. However, a thorough review of the literature
      reveals that effective teaching strategies, including simulation, in regional
      anesthesiology and acute pain medicine are not established completely yet. Future
      research should be directed toward comparative-effectiveness of simulation versus
      other accepted teaching methods, exploring the combination of procedural training
      with realistic clinical scenarios, and the application of simulation-based
      teaching curricula to a wider range of learner, from the student to the
      practicing physician. 

PMID- 26316813
TI  - Regional anesthesia for the trauma patient: improving patient outcomes.
AB  - Trauma is a significant health problem and a leading cause of death in all age
      groups. Pain related to trauma is frequently severe, but is often undertreated in
      the trauma population. Opioids are widely used to treat pain in injured patients
      but have a broad range of undesirable effects in a multitrauma patient such as
      neurologic and respiratory impairment and delirium. In contrast, regional
      analgesia confers excellent site-specific pain relief that is free from major
      side effects, reduces opioid requirement in trauma patients, and is safe and easy
      to perform. Specific populations that have shown benefits (including morbidity
      and mortality advantages) with regional analgesic techniques include those with
      fractured ribs, femur and hip fractures, and patients undergoing digital
      replantation. Acute compartment syndrome is a potentially devastating sequela of
      soft-tissue injury that complicates high-energy injuries such as proximal tibia
      fractures. The use of regional anesthesia in patients at risk for compartment
      syndrome is controversial; although the data is sparse, there is no evidence that
      peripheral nerve blocks delay the diagnosis, and these techniques may in fact
      facilitate the recognition of pathologic breakthrough pain. The benefits of
      regional analgesia are likely most influential when it is initiated as early as
      possible, and the performance of nerve blocks both in the emergency room and in
      the field has been shown to provide quality pain relief with an excellent safety
      profile. 

PMID- 26316814
TI  - Ophthalmic regional blocks: management, challenges, and solutions.
AB  - In the past decade ophthalmic anesthesia has witnessed a major transformation.
      The sun has set on the landscape of ophthalmic procedures performed under general
      anesthesia at in-hospital settings. In its place a new dawn has ushered in the
      panorama of eye surgeries conducted under regional and topical anesthesia at
      specialty eye care centers. The impact of the burgeoning geriatric population is
      that an increasing number of elderly patients will present for eye surgery. In
      order to accommodate increased patient volumes and simultaneously satisfy
      administrative initiatives directed at economic frugality, administrators will
      seek assistance from anesthesia providers in adopting measures that enhance
      operating room efficiency. The performance of eye blocks in a holding suite meets
      many of these objectives. Unfortunately, most practicing anesthesiologists resist
      performing ophthalmic regional blocks because they lack formal training. In
      future, anesthesiologists will need to block eyes and manage common medical
      conditions because economic pressures will eliminate routine preoperative
      testing. This review addresses a variety of topical issues in ophthalmic
      anesthesia with special emphasis on cannula and needle-based blocks and the new
      generation antithrombotic agents. In a constantly evolving arena, the sub-Tenon's
      block has gained popularity while the deep angulated intraconal (retrobulbar)
      block has been largely superseded by the shallower extraconal (peribulbar)
      approach. Improvements in surgical technique have also impacted anesthetic
      practice. For example, phacoemulsification techniques facilitate the conduct of
      cataract surgery under topical anesthesia, and suture-free vitrectomy ports may
      cause venous air embolism during air/fluid exchange. Hyaluronidase is a useful
      adjuvant because it promotes local anesthetic diffusion and hastens block onset
      time but it is allergenic. Ultrasound-guided eye blocks afford real-time
      visualization of needle position and local anesthetic spread. An advantage of
      sonic guidance is that it may eliminate the hazard of globe perforation by
      identifying abnormal anatomy, such as staphyloma. 

PMID- 26316815
TI  - Molecular heterogeneity in adjacent cells in triple-negative breast cancer.
AB  - PURPOSE: This study interrogates the molecular status of individual cells in
      patients with triple-negative breast cancers and explores the molecular
      identification and characterization of these tumors to consider the exploitation
      of a potential-targeted therapeutic approach. PATIENTS AND METHODS: Hyperspectral
      immunologic cell by cell analysis was applied to touch imprint smears obtained
      from fresh tumors of breast cancer patients. RESULTS: Cell by cell analysis
      confirms significant intratumoral molecular heterogeneity in cancer markers with
      differences from polymerase chain reaction marker reporting. The individual cell
      heterogeneity was recognized in adjacent cells examined with panels of ten
      molecular markers in each single cell and included some markers that are
      considered to express "stem-cell" character. In addition, heterogeneity did not
      relate either to the size or stage of the primary tumor or to the site from
      within the cancer. CONCLUSION: There is a very significant molecular
      heterogeneity when "adjacent cells" are examined in triple-negative breast
      cancer, thereby making a successful targeted approach unlikely. In addition, it
      is not reasonable to consider that these changes will provide an answer to tumor
      dormancy.

PMID- 26316816
TI  - Triple negative breast cancer: an Indian perspective.
AB  - INTRODUCTION: Breast cancer is the most common female cancer in the world. Triple
      negative breast cancer (TNBC) is a recently identified biological variant with
      aggressive tumor behavior and poor prognosis. Data of hormonal status from the
      Indian population is scarce due to financial constraints in performing
      immunohistochemistry evaluation. The present study aims to prospectively analyze
      receptor status of all breast cancer patients and identify TNBC and compare their
      clinical profile and short term survival with other non-TNBC group. MATERIALS AND
      METHODS: All cytologically and histopathologically confirmed cases of carcinoma
      breast were prospectively enrolled. In a longitudinal study at tertiary care
      hospital in central India based on the hormonal status, they were further divided
      into TNBC and other groups. Comparison of risk factors, clinical profile and
      short-term survival was carried out. RESULTS: A total 85 patients were enrolled
      and of them 37 (43.7%) were TNBC. On comparing risk factors ie, age, age at
      menarche, total reproductive age, age at first child birth, and menopausal status
      - no statistical significance was observed between the TNBC and non-TNBC groups.
      But on comparison of clinical profile TNBC tumors were significantly large with
      majority of patients presenting as locally advanced breast cancer (83%). No
      statistical difference was observed in axillary lymph node status between two
      groups. TNBC tumors were histologically more aggressive (grade 3) compared to
      other groups. No statistically significant difference was observed in short term
      overall survival but all three deaths were observed in the TNBC group only and
      two local recurrences after surgery were observed in the TNBC group. CONCLUSION:
      TNBC forms a large proportion of carcinoma breast patients in a central Indian
      scenario and needs more research to identify appropriate treatment planning
      considering aggressive histology and advanced presentation.

PMID- 26316818
TI  - The treatment landscape in thyroid cancer: a focus on cabozantinib.
AB  - Although patients with thyroid cancer generally fare well, there is a subset for
      which this is not necessarily true. Progress in understanding the molecular
      aberrations in thyroid cancer has led to a change in the management of these
      cases. Since 2011, four multikinase inhibitors (MKIs) have been approved by the
      US Food and Drug Administration for thyroid cancer - cabozantinib and vandetanib
      for medullary thyroid cancer and sorafenib and lenvatinib for differentiated
      thyroid cancer. This change in the treatment landscape has raised challenges for
      practitioners who may not be familiar with the use of MKIs or with the treatment
      and natural history of advanced thyroid cancer in general. This article reviews
      the epidemiology, molecular drivers, and initial treatment of patients with
      thyroid cancer and offers practical guidance to assist with the determination of
      when to appropriately start an MKI. As an example, cabozantinib and its efficacy
      are discussed in detail. Close monitoring is required for all patients on
      targeted agents to assess for adverse effects and response to therapy. An
      approach to managing drug-related adverse events is detailed. Since these drugs
      are not curative and have not yet proven to prolong overall survival, it is
      critical to weigh the risks and benefits of treatment at every visit. The
      potential value of changing to a different agent following failure of an MKI is
      also addressed. 

PMID- 26316817
TI  - Progress toward overcoming hypoxia-induced resistance to solid tumor therapy.
AB  - Hypoxic tumors are associated with poor clinical outcome for multiple types of
      human cancer. This may be due, in part, to hypoxic cancer cells being resistant
      to anticancer therapy, including radiation therapy, chemotherapy, and targeted
      therapy. Hypoxia inducible factor 1, a major regulator of cellular response to
      hypoxia, regulates the expression of genes that are involved in multiple aspects
      of cancer biology, including cell survival, proliferation, metabolism, invasion,
      and angiogenesis. Here, we review multiple pathways regulated by hypoxia/hypoxia
      inducible factor 1 in cancer cells and discuss the latest advancements in
      overcoming hypoxia-mediated tumor resistance. 

PMID- 26316820
TI  - SpineData - a Danish clinical registry of people with chronic back pain.
AB  - BACKGROUND: Large-scale clinical registries are increasingly recognized as
      important resources for quality assurance and research to inform clinical
      decision-making and health policy. We established a clinical registry (SpineData)
      in a conservative care setting where more than 10,000 new cases of spinal pain
      are assessed each year. This paper describes the SpineData registry, summarizes
      the characteristics of its clinical population and data, and signals the
      availability of these data as a resource for collaborative research projects.
      METHODS: The SpineData registry is an Internet-based system that captures patient
      data electronically at the point of clinical contact. The setting is the
      government-funded Medical Department of the Spine Centre of Southern Denmark,
      Hospital Lillebaelt, where patients receive a multidisciplinary assessment of
      their chronic spinal pain. RESULTS: Started in 2011, the database by early 2015
      contained information on more than 36,300 baseline episodes of patient care, plus
      the available 6-month and 12-month follow-up data for these episodes. The
      baseline questionnaire completion rate has been 93%; 79% of people were
      presenting with low back pain as their main complaint, 6% with mid-back pain, and
      15% with neck pain. Collectively, across the body regions and measurement time
      points, there are approximately 1,980 patient-related variables in the database
      across a broad range of biopsychosocial factors. To date, 36 research projects
      have used data from the SpineData registry, including collaborations with
      researchers from Denmark, Australia, the United Kingdom, and Brazil. CONCLUSION:
      We described the aims, development, structure, and content of the SpineData
      registry, and what is known about any attrition bias and cluster effects in the
      data. For epidemiology research, these data can be linked, at an individual
      patient level, to the Danish population-based registries and the national spinal
      surgery registry. SpineData also has potential for the conduct of cohort multiple
      randomized controlled trials. Collaborations with other researchers are welcome.

PMID- 26316819
TI  - Hospital use among patients with lung cancer complicated by bone metastases and
      skeletal- related events: a population-based cohort study in Denmark.
AB  - OBJECTIVE: Skeletal-related events (SREs) among patients with bone metastases
      from lung cancer may be associated with considerable use of health care
      resources. We analyzed in- and outpatient hospital contacts in relation to SREs
      among all Danish lung cancer patients with bone metastases. METHODS: For this
      cohort study, we used the Danish Cancer Registry and the Danish National Registry
      of Patients to identify all persons diagnosed with first-time lung cancer and
      bone metastases from 2003 through 2009 in Denmark. We followed these patients
      until December 31, 2010, for the development of SREs (spinal cord compression;
      pathological or osteoporotic fracture, surgery to bone; or conventional external
      radiation therapy). We examined the number of inpatient hospitalizations,
      inpatient bed-days, hospital outpatient clinic visits, and emergency room visits
      within three time periods: a pre-SRE period (90-day period prior to the
      diagnostic period), a SRE diagnostic period (14-day period prior to the SRE), and
      a post-SRE period (90-day period after the SRE). RESULTS: We identified 1,146
      patients with lung cancer, bone metastases, and >=1 subsequent SRE among 28,443
      patients with incident lung cancer. Over 75% of patients with SREs (n=852) had
      more than one SRE. The number of hospital bed-days was high in the post-SRE
      period compared to the pre-SRE period, as illustrated by patients with multiple
      SREs who had 10.7 (95% confidence interval, 10.4-10.9) hospital bed-days per 100
      person-days in the pre-SRE period and 28.2 (95% confidence interval, 27.8-28.6)
      bed-days per 100 person-days in the post-SRE period. CONCLUSION: SREs secondary
      to bone metastases in lung cancer patients are associated with a substantial
      number of hospital contacts and hospital bed-days.

PMID- 26316821
TI  - Multi-disciplinary approach for enhancing orthodontic esthetics - case report.
AB  - BACKGROUND: In contemporary dental care, an increasing number of adult patients
      are now seeking orthodontic treatment with the primary motive of improvement in
      appearance and achievement of esthetic smile. Proper recognition of the dental
      and facial defects at the outset of treatment is the most important key to
      esthetic success and is essential in satisfying the patient's needs. By following
      the rules of Golden proportion smiles can be made attractive, harmonious,
      symmetrical, and proportionate. METHODOLOGY: Consisted of 22-year-old girl who
      came for treatment of crowding in maxillary and mandibular arches, abnormal
      overjet and overbite and had unesthetic peg lateral. RESULTS: Non-extraction
      therapy was carried out since the patient had good soft tissue drape, alignment
      was achieved by expanding the arches and moving teeth in ideal axial inclination.
      Esthetic smile was attained using composite buildup of upper right peg lateral
      and minor adjunctive surgery (full thickness periodontal graft) on lower right
      central incisor. CONCLUSION: The present case report orchestrates
      interrelationship between various branches of dentistry and orthodontics. It
      exhibits how multidisciplinary approach can be used to achieve ideal dental
      esthetics in a 22-year-old girl who was successfully treated for peg shaped
      lateral incisor, gingival recession, and unesthetic smile.

PMID- 26316822
TI  - The effectiveness and limitations of regulatory warnings for the safe prescribing
      of citalopram.
AB  - BACKGROUND: Citalopram is the most commonly prescribed antidepressant in Canada.
      Concerns have been raised about its cardiac safety, and a dose-dependent
      prolongation of the QT interval has been documented. Drug interactions involving
      concomitant use of other medications that prolong the QT interval or increase
      citalopram levels by interfering with its metabolism increase the cardiac risk.
      Regulatory bodies (Health Canada and the US Food and Drug Administration) issued
      warnings and required labeling changes in 2011/2012, suggesting maximum
      citalopram doses (<40 mg for those <65 years; <20 mg for those >=65 years) and
      avoiding drug interactions that increase cardiac risk. The purpose of this study
      is to assess the impact of these warnings on citalopram prescribing practices.
      METHODS: A quasi-experimental interrupted time series analysis was conducted
      using all citalopram prescribing data from the population of Manitoba, Canada
      from 1999 to 2014. This allowed for the examination of high-dose prescribing
      (above regulatory warning levels) and the number of interacting medications per
      citalopram prescription. RESULTS: There was a dramatic decline in the prescribing
      of high doses in both age groups, with a 64.8% decline in those <65 years and
      33.6% in those >=65 years. Segmented regression models indicated significant
      breakpoints in the third quarter of 2011 for both age groups (P<0.0001),
      corresponding to the time the regulatory warnings were issued. There appeared to
      be no impact of the warnings on the prescribing of interacting medications. The
      number of interacting medications actually increased in the postwarning period
      (<65, 0.78-0.81 interactions per citalopram prescription; >=65, 0.93-0.94,
      P<0.001). CONCLUSION: Regulatory changes appear to have produced an important
      reduction in the high-dose prescribing of citalopram. In contrast to this
      relatively simple dosage change, there was no indication that the more complex
      issue of resolving drug-drug interactions was impacted by regulatory warnings.

PMID- 26316825
TI  - Spontaneous rupture of multifocal hepatocellular carcinoma: case report.
AB  - Hemoperitoneum due to nontraumatic liver rupture is rare. The most common cause
      of nontraumatic rupture of the liver is hepatocellular carcinoma (HCC). The other
      causes of nontraumatic liver ruptures are peliosis hepatis, polyarteritis nodosa,
      systemic lupus erythematosus, preeclampsia, metastatic carcinoma, and other
      primary liver tumors. In this report, we present the computed tomography findings
      of spontaneous liver rupture in a 52-year-old male patient due to multifocal HCC,
      with the diagnosis proven by surgical specimen. 

PMID- 26316824
TI  - Migraine in menopausal women: a systematic review.
AB  - Evidence suggests that migraine activity is influenced by hormonal factors, and
      particularly by estrogen levels, but relatively few studies have investigated the
      prevalence and characteristics of migraine according to the menopausal status.
      Overall, population-based studies have shown an improvement of migraine after
      menopause, with a possible increase in perimenopause. On the contrary, the
      studies performed on patients referring to headache centers have shown no
      improvement or even worsening of migraine. Menopause etiology may play a role in
      migraine evolution during the menopausal period, with migraine improvement more
      likely occurring after spontaneous rather than after surgical menopause.
      Postmenopausal hormone replacement therapy has been found to be associated with
      migraine worsening in observational population-based studies. The effects of
      several therapeutic regimens on migraine has also been investigated, leading to
      nonconclusive results. To date, no specific preventive measures are recommended
      for menopausal women with migraine. There is a need for further research in order
      to clarify the relationship between migraine and hormonal changes in women, and
      to quantify the real burden of migraine after the menopause. Hormonal
      manipulation for the treatment of refractory postmenopausal migraine is still a
      matter of debate. 

PMID- 26316823
TI  - Identification of risk factors for hepatitis B and C in Peshawar, Pakistan.
AB  - BACKGROUND: Hepatitis B and C need immediate worldwide attention as the infection
      rates are too high. More than 240 million people have chronic (long-term) liver
      infections. Every year, about 600,000 people die globally due to the acute or
      chronic consequences of hepatitis B and more than 350,000 people die from
      hepatitis C-related liver diseases. METHODS: Our study was designed as a case
      control, descriptive study. It was conducted through formal interviews by using
      structured questionnaires. A total of 100 cases were included, with four controls
      for each case. RESULTS: This study confirms household contact, history of dental
      work, history of surgery, sexual contact, and history of transfusion (blood and
      its components) as the main risk factors which are responsible for the increased
      prevalence of hepatitis. CONCLUSION: The important risk factors, responsible for
      the high prevalence of hepatitis B and C in our society are household contact,
      history of dental work, history of surgery, sexual contact, and history of
      transfusion (blood and its components). The odds ratio of probability for these
      risk factors are: 4.2 for household contact history, 4.1 for history of dental
      work, 3.9 for sexual contact, 2.7 for history of surgery, and 2.1 for history of
      transfusion. Associations of other predictor variables (diabetes status,
      education level, profession, contact sports, intravenous drug abuse, residence,
      immunosuppression, and skin tattoos) were not statistically significant.

PMID- 26316826
TI  - Negative pressure pulmonary edema after nasal fracture reduction in an obese
      female patient: a case report.
AB  - Postoperative negative pressure pulmonary edema (NPPE) is a rare, but well-known
      life-threatening complication of acute upper airway obstruction (UAO) which
      develops after general anesthesia. The pronounced inspiratory efforts following
      UAO lead to excessive negative inspiratory pressure, which may cause acute
      pulmonary edema. Early recognition and prompt treatment of NPPE is necessary to
      prevent patient morbidity and mortality. In addition, the physician should
      carefully manage the patient who has risk factors of UAO to prevent this
      situation. We experienced a case of NPPE following laryngospasm after tracheal
      extubation in an obese patient who underwent open reduction of orbital wall and
      nasal bone surgery. 

PMID- 26316827
TI  - Dual-sided electrosurgery handpiece for simultaneous tissue cutting and
      coagulation: first report on a conceptual design validated by an animal
      experiment.
AB  - OBJECTIVE: To introduce and evaluate the safety of a novel dual-sided
      electrosurgery handpiece design for simultaneous tissue cutting and coagulation.
      METHODS: We designed a prototype double-sided handpiece allowing automatic
      switching between two electrodes with a simple handpiece flip. The concept of the
      system as a surgical instrument was assessed by an animal experiment. RESULTS:
      The skin of 15 Wistar albino white rats could be successfully incised and
      coagulated using both ends of the handpiece, thereby confirming the prospects and
      clinical applications of the system. CONCLUSION: The dual-sided electrosurgery
      handpiece is a simple and safe alternative to the traditional electrosurgery
      pencil, allowing the simultaneous use of two electrodes without the hassle of
      frequent electrode replacement.

PMID- 26316829
TI  - Reliability and criterion-related validity of the 20-yard shuttle test in
      competitive junior tennis players.
AB  - PURPOSE: This study adds to the previous work in the field of sport-specific
      fitness testing by evaluating a tennis-specific agility test called "the 20-yard
      shuttle test". The aim of the study was to evaluate the test-retest reliability,
      the inter-rater reliability, and the criterion-related validity of the 20-yard
      shuttle test on competitive junior tennis players. PARTICIPANTS AND METHODS:
      Totally, 34 Swedish tennis players (13 girls), mean age 14+/-1.6 years,
      participated in the study. To examine test-retest reliability, the subjects
      performed the 20-yard shuttle test three times on the same day and then the same
      procedure was repeated after 3 days. To test the inter-rater reliability, the
      time was measured with a stopwatch simultaneously by two different raters. The
      time recorded manually was compared to the gold standard of digital timing to
      evaluate the criterion-related validity. RESULTS: Excellent test-retest
      reliability was found both within the same day (intraclass correlation
      coefficient [ICC] 0.95) and between days (ICC 0.91). Furthermore, the results
      showed excellent inter-rater reliability (ICC 0.99) and criterion-related
      validity on both test occasions (ICC 0.99). CONCLUSION: We have provided
      introductory support for the 20-yard shuttle test as a reliable and valid test
      for use in competitive junior tennis players. The ease of administration makes
      this test a practical alternative to evaluate physical fitness in order to
      optimally train the athletes.

PMID- 26316828
TI  - Role of nutrition in performance enhancement and postexercise recovery.
AB  - A number of factors contribute to success in sport, and diet is a key component.
      An athlete's dietary requirements depend on several aspects, including the sport,
      the athlete's goals, the environment, and practical issues. The importance of
      individualized dietary advice has been increasingly recognized, including day-to
      day dietary advice and specific advice before, during, and after training and/or
      competition. Athletes use a range of dietary strategies to improve performance,
      with maximizing glycogen stores a key strategy for many. Carbohydrate intake
      during exercise maintains high levels of carbohydrate oxidation, prevents
      hypoglycemia, and has a positive effect on the central nervous system. Recent
      research has focused on athletes training with low carbohydrate availability to
      enhance metabolic adaptations, but whether this leads to an improvement in
      performance is unclear. The benefits of protein intake throughout the day
      following exercise are now well recognized. Athletes should aim to maintain
      adequate levels of hydration, and they should minimize fluid losses during
      exercise to no more than 2% of their body weight. Supplement use is widespread in
      athletes, with recent interest in the beneficial effects of nitrate, beta
      alanine, and vitamin D on performance. However, an unregulated supplement
      industry and inadvertent contamination of supplements with banned substances
      increases the risk of a positive doping result. Although the availability of
      nutrition information for athletes varies, athletes will benefit from the advice
      of a registered dietician or nutritionist. 

PMID- 26316830
TI  - Resilience in young people living with violence and self-harm: evidence from a
      Norwegian national youth survey.
AB  - The aim of this article is to explore the relationship between resilience and the
      psychological problems of young people who reported being victims of violence and
      who engaged in self-harm. We used data from a national survey conducted in 2007
      asking young people in Norway (N=6,034; ages 18-19 years) about their experiences
      with violence during their childhood and during the past 12 months, and also
      about their mental health and experiences of self-harm. Our analyses revealed
      that resilience, as measured by the Resilience Scale for Adolescents, correlates
      significantly and negatively with psychological problems among all young people,
      and that this correlation is substantially stronger for those youths who reported
      violent experiences and those who engaged in self-harm. 

PMID- 26316831
TI  - Identity development, intelligence structure, and interests: a cross-sectional
      study in a group of Italian adolescents during the decision-making process.
AB  - BACKGROUND: Forming one's identity is thought to be the key developmental task of
      adolescence, but profound changes in personality traits also occur in this
      period. The negotiation of complex social settings, the creation of an integrated
      identity, and career choice are major tasks of adolescence. The adolescent,
      having to make choices for his or her future, has not only to consider his or her
      own aspirations and interests but also to possess a capacity for exploration and
      commitment; in fact, career commitments can be considered as a fit between the
      study or career that is chosen and personal values, skills, and preferences.
      METHODS: The objective of the study reported here was to investigate the role of
      identity on profile of interests; the relation between identity and decisional
      style; the correlation between identity, aptitudes, interests, and school
      performance; and the predictive variables to school success. The research
      involved 417 Italian students who live in Enna, a small city located in Sicily,
      Italy, aged 16-19 years (197 males and 220 females) in the fourth year (mean
      =17.2, standard deviation =0.52) and the fifth year (mean =18.2, standard
      deviation =0.64) of senior secondary school. The research lasted for one school
      year; the general group of participants consisted of 470 students, and although
      all participants agreed to be part of the research, there was a dropout rate of
      11.28%. They completed the Ego Identity Process Questionnaire to measure their
      identity development, the Intelligence Structure Test to investigate aptitudes,
      the Self-Directed Search to value interests, and General Decision Making Style
      questionnaire to describe their individual decisional style. RESULTS: The data
      showed that high-school performance was positively associated with rational
      decision-making style and identity diffusion predicted the use of avoidant style.
      Interests were related to identity exploration; the differentiation of
      preferences was related to identity commitment; investigative personality
      correlated with the rational style and negatively with the spontaneous style and
      high levels of school performance; and social personality correlated with the use
      of the spontaneous style and the intuitive style, a high-profile identity, and
      identity exploration. CONCLUSION: Intervention in the development of the identity
      process proves to be fundamental for increasing aptitudes and improving school
      performance, and, above all, for broadening the diversification and coherence of
      interests and improving the decisional process.

PMID- 26316832
TI  - Recent trends in reproductive tourism and international surrogacy: ethical
      considerations and challenges for policy.
AB  - Reproductive tourism, or "cross-border reproductive care", is the phenomenon of
      people crossing international borders to access reproductive technologies. One of
      the fastest-growing categories of cross-border reproductive care is international
      surrogacy, the act of infertile clients traveling internationally to engage the
      paid services of foreign surrogates to carry their babies to term. It is a
      multibillion-dollar global industry presenting unique legal, ethical, and risk
      management challenges. Clients tend to be price-sensitive, middle-income
      individuals seeking services from surrogates who in the global market are thought
      to be of quite low socioeconomic status. Risks are experienced by all parties
      involved in the transaction, including the client's countries of origin and
      destination. The risks to the surrogate evolve from the potential to exploit her
      economic vulnerability in order to encourage both consent and unfair pricing.
      Opportunities for policy development are explored. 

PMID- 26316833
TI  - Developing a handheld record for patients with cystic fibrosis.
AB  - Patient handheld records (PHHRs) promote self-management and empower the holder
      to take a more active role in the management of their disease. They have been
      used successfully in improving preventative care for children and have
      contributed to improved adherence in a number of chronic illnesses. Despite the
      potential advantages, there are no standard PHHRs for patients with cystic
      fibrosis (CF). We report the consultation process that led to the development of
      a CF PHHR, describe the final document, and analyze the feedback from their use
      at our center. We have made the CF PHHR freely available online. 

PMID- 26316835
TI  - A review of mobile applications to help adolescent and young adult cancer
      patients.
AB  - OBJECTIVE: To review research articles utilizing mobile applications with
      adolescent and young adult (AYA) cancer patients. MATERIALS AND METHODS: We
      identified articles via online searches and reference lists (eg, PsycInfo,
      PubMed). Articles were reviewed by two study team members for target population,
      stated purpose, technological utilization, sample size, demographic
      characteristics, and outcome data. Strengths and weaknesses of each study were
      described. RESULTS: Of 19 identified manuscripts, six met full inclusion criteria
      for this review (four smartphone applications and two tablet applications). One
      additional article that included an application not specific to oncology but
      included AYA patients with cancer within the target sample was also reviewed.
      Uses of these applications included symptom tracking, pain management, monitoring
      of eating habits following bone marrow transplant, monitoring of mucositis, and
      improving medication management. Utility results from pilot studies are
      presented. CONCLUSION: Mobile applications are growing in number and increasingly
      available to AYAs with and without chronic illness. These applications may prove
      useful in helping to support AYAs throughout their cancer treatment and beyond.
      However, few applications provide empirical data supporting their utility.
      Numerous strengths and benefits of these applications include increased
      accessibility to educational resources and self-management strategies, more
      frequent physical and emotional symptom tracking, and increased access to peer
      support. Despite these strengths, numerous limitations are identified,
      highlighting the need for future research in this area.

PMID- 26316836
TI  - Cross-cultural challenges for assessing medical professionalism among clerkship
      physicians in a Middle Eastern country (Bahrain): feasibility and psychometric
      properties of multisource feedback.
AB  - BACKGROUND: We aimed to design, implement, and evaluate the feasibility and
      reliability of a multisource feedback (MSF) system to assess interns in their
      clerkship year in the Middle Eastern culture, the Kingdom of Bahrain. METHOD: The
      study was undertaken in the Bahrain Defense Force Hospital, a military teaching
      hospital in the Kingdom of Bahrain. A total of 21 interns (who represent the
      total population of the interns for the given year) were assessed in this study.
      All of the interns were rotating through our hospital during their year-long
      clerkship rotation. The study sample consisted of nine males and 12 females. Each
      participating intern was evaluated by three groups of raters, eight medical
      intern colleagues, eight senior medical colleagues, and eight coworkers from
      different departments. RESULTS: A total of 21 interns (nine males and 12 females)
      were assessed in this study. The total mean response rates were 62.3%. A factor
      analysis was conducted that found that the data on the questionnaire grouped into
      three factors that counted for 76.4% of the total variance. These three factors
      were labeled as professionalism, collaboration, and communication. Reliability
      analysis indicated that the full instrument scale had high internal consistency
      (Cronbach's alpha 0.98). The generalizability coefficients for the surveys were
      estimated to be 0.78. CONCLUSION: Based on our results and analysis, we conclude
      that the MSF tool we used on the interns rotating in their clerkship year within
      our Middle Eastern culture provides an effective method of evaluation because it
      offers a reliable, valid, and feasible process.

PMID- 26316834
TI  - Controlling myopia progression in children and adolescents.
AB  - Myopia is a common disorder, affecting approximately one-third of the US
      population and over 90% of the population in some East Asian countries. High
      amounts of myopia are associated with an increased risk of sight-threatening
      problems, such as retinal detachment, choroidal degeneration, cataracts, and
      glaucoma. Slowing the progression of myopia could potentially benefit millions of
      children in the USA. To date, few strategies used for myopia control have proven
      to be effective. Treatment options such as undercorrection of myopia, gas
      permeable contact lenses, and bifocal or multifocal spectacles have all been
      proven to be ineffective for myopia control, although one recent randomized
      clinical trial using executive top bifocal spectacles on children with
      progressive myopia has shown to decrease the progression to nearly half of the
      control subjects. The most effective methods are the use of orthokeratology
      contact lenses, soft bifocal contact lenses, and topical pharmaceutical agents
      such as atropine or pirenzepine. Although none of these modalities are US Food
      and Drug Administration-approved to slow myopia progression, they have been shown
      to slow the progression by approximately 50% with few risks. Both orthokeratology
      and soft bifocal contact lenses have shown to slow myopia progression by slightly
      less than 50% in most studies. Parents and eye care practitioners should work
      together to determine which modality may be best suited for a particular child.
      Topical pharmaceutical agents such as anti-muscarinic eye drops typically lead to
      light sensitivity and poor near vision. The most effective myopia control is
      provided by atropine, but is rarely prescribed due to the side effects.
      Pirenzepine provides myopia control with little light sensitivity and few near
      vision problems, but it is not yet commercially available as an eye drop or
      ointment. Several studies have shown that lower concentrations of atropine slow
      the progression of myopia control with fewer side effects than 1% atropine. While
      the progression of myopic refractive error is slowed with lower concentration of
      atropine, the growth of the eye is not, indicating a potentially reversible form
      of myopia control that may diminish after discontinuation of the eye drops. This
      review provides an overview of the myopia control information available in the
      literature and raises questions that remain unanswered, so that eye care
      practitioners and parents can potentially learn the methods that may ultimately
      improve a child's quality of life or lower the risk of sight-threatening
      complications. 

PMID- 26316837
TI  - Residency program characteristics that are associated with pass rate of the
      American Board of Pediatrics certifying exam.
AB  - BACKGROUND: The US is home to almost 200 pediatrics residency programs; despite
      this, there is little information about the relationship between program
      characteristics and performance in the American Board of Pediatrics (ABP)
      certifying exam. OBJECTIVE: To evaluate the relationship between pass rate of the
      ABP certifying exam with the characteristics of categorical pediatrics residency
      programs. METHODS: This retrospective, cross-sectional study used publicly
      available data from the ABP website and the Fellowship and Residency Electronic
      Interactive Database. All programs that reported pass rates were included. The
      analysis, comprising univariate and multivariate linear regression, involved
      determining how 69 factors (eg, general information, number of faculty and
      trainees, work schedule, educational environment) related to the pass rate.
      RESULTS: Of 199 programs, 194 reported pass rates. The univariate analysis
      revealed 20 program characteristics with P-values <0.10. However, in the
      multivariate analysis, pass rate was significantly associated with only three
      program characteristics: ratio of full-time equivalent paid faculty to positions,
      percentage of US medical graduates, and average hours per week of regularly
      scheduled lectures or conferences. CONCLUSION: Unlike in previous studies,
      location and program size were not significantly associated with the pass rate in
      this multivariate analysis. The finding regarding the ratio of full-time
      equivalent paid faculty to positions highlighted the benefits of a well
      supervised training environment, while that regarding the percentage of US
      medical graduates indicated the necessity of high competition in residency
      programs. Finally, longer hours per week of regularly scheduled lectures or
      conferences were associated with better academic outcomes, both statistically and
      intuitively.

PMID- 26316838
TI  - Opioid-use disorder among patients on long-term opioid therapy: impact of final
      DSM-5 diagnostic criteria on prevalence and correlates.
AB  - AIMS: Previously, we estimated the prevalence and risk factors for prescription
      opioid-use disorder among outpatients on opioid therapy using the Diagnostic and
      Statistical Manual of Mental Disorders (DSM)-5 and DSM-4 criteria. However, at
      the time, the DSM-5 criteria were not finalized. In the current study, we
      analyzed these data using the final DSM-5 criteria and compared these results.
      METHODS: Using electronic records from a large US health care system, we
      identified outpatients receiving five or more prescription orders for opioid
      therapy in the past 12 months for noncancer pain (mean prescription orders
      =10.72; standard deviation =4.96). In 2008, we completed diagnostic interviews
      with 705 of these patients using the DSM-4 criteria. In the current study, we
      reassessed these results using the final DSM-5 criteria. RESULTS: The lifetime
      prevalence of DSM-5 opioid-use disorders using the final DSM-5 criteria was 58.7%
      for no or few symptoms (<2), 28.1% for mild symptoms (2-3), 9.7% for moderate
      symptoms (4-5), and 3.5% for severe symptoms (six or more). Thus, the lifetime
      prevalence of "any" prescription opioid-use disorder in this cohort was 41.3%
      (95% confidence interval [CI] =37.6-45.0). A comparison to the DSM-4 criteria
      indicated that the majority of patients with lifetime DSM-4 opioid dependence
      were now classified as having mild opioid-use disorder, based on the DSM-5
      criteria (53.6%; 95% CI =44.1-62.8). In ordinal logistic regression predicting
      no/few, mild, moderate, and severe opioid-use disorder, the best predictors were
      age <65 years, current pain impairment, trouble sleeping, suicidal thoughts,
      anxiety disorders, illicit drug use, and history of substance abuse treatment.
      CONCLUSION: Given the final DSM-5 criteria, including the elimination of
      tolerance and withdrawal, inclusion of craving and abuse symptoms, and
      introduction of a new graded severity classification, the prevalence of opioid
      use disorders has changed, while many of the DSM-4 risk factors for opioid
      dependence were similar. To our knowledge, this is one of the first studies to
      compare the final results for DSM-5 versus DSM-4 prescription opioid-use
      disorders among a high-risk patient population.

PMID- 26316839
TI  - Genome-wide prediction of three important traits in bread wheat.
AB  - Five genomic prediction models were applied to three wheat agronomic traits-grain
      yield, heading date and grain test weight-in three breeding populations, each
      comprising about 350 doubled haploid or recombinant inbred lines evaluated in
      three locations during a 3-year period. The prediction accuracy, measured as the
      correlation between genomic estimated breeding value and observed trait, was in
      the range of previously published values for yield (r = 0.2-0.5), a trait with
      relatively low heritability. Accuracies for heading date and test weight, with
      relatively high heritabilities, were about 0.70. There was no improvement of
      prediction accuracy when two or three breeding populations were merged into one
      for a larger training set (e.g., for yield r ranged between 0.11 and 0.40 in the
      respective populations and between 0.18 and 0.35 in the merged populations).
      Cross-population prediction, when one population was used as the training
      population set and another population was used as the validation set, resulted in
      no prediction accuracy. This lack of cross-population prediction accuracy cannot
      be explained by a lower level of relatedness between populations, as measured by
      a shared SNP similarity, since it was only slightly lower between than within
      populations. Simulation studies confirm that cross-prediction accuracy decreases
      as the proportion of shared QTLs decreases, which can be expected from a higher
      level of QTL * environment interactions.

PMID- 26316840
TI  - The dual role of phytoene synthase genes in carotenogenesis in carrot roots and
      leaves.
AB  - Carrot (Daucus carota L.) is an important food crop and is useful for studying
      carotenogenesis due to the quantity and diversity of carotenoids in its roots.
      Phytoene synthase catalyzes the first committed step in the carotenoid
      biosynthesis pathway, and its overexpression is the main driving force in the
      orange phenotype. At present, we lack fundamental knowledge of the role of these
      genes and their effects on carotenoid accumulation in leaves. In the present
      study, three backcross inbred lines (BC2S4) with different colored roots derived
      from a cross between the orange inbred line (Af) and related wild species were
      used to investigate the role of the duplicated DcPSY genes in root
      carotenogenesis. Promoter analysis showed that DcPSY genes have diverged
      substantially in their regulatory sequences after gene duplication. Expression
      levels of DcPSY1 and DcPSY2 were generally positively correlated with carotenoid
      content during root development. In mature leaves, total carotenoid content was
      higher than that in the roots, DcPSY1 expression increased extremely higher than
      DcPSY2 expression compared with roots, and DcPSY1 was more sensitive than DcPSY2
      during leaf de-etiolation under sunlight. These results suggest that DcPSY1 seems
      to make an important contribution to carotenoid accumulation in the leaves and is
      important for photosynthesis and photoprotection, but they are not the
      determining factors of root color. This expands our understanding of the
      regulation of carotenoid biosynthesis in carrot.

PMID- 26316842
TI  - Invaders in hot water: a simple decontamination method to prevent the accidental
      spread of aquatic invasive non-native species.
AB  - Watersports equipment can act as a vector for the introduction and spread of
      invasive non native species (INNS) in freshwater environments. To support advice
      given to recreational water users under the UK Government's Check Clean Dry
      biosecurity campaign and ensure its effectiveness at killing a range of aquatic
      INNS, we conducted a survival experiment on seven INNS which pose a high risk to
      UK freshwaters. The efficacy of exposure to hot water (45  degrees C, 15 min) was
      tested as a method by which waters users could 'clean' their equipment and was
      compared to drying and a control group (no treatment). Hot water had caused 99 %
      mortality across all species 1 h after treatment and was more effective than
      drying at all time points (1 h: chi2 = 117.24, p < 0.001; 1 day chi2 = 95.68, p <
      0.001; 8 days chi2 = 12.16, p < 0.001 and 16 days chi2 = 7.58, p < 0.001). Drying
      caused significantly higher mortality than the control (no action) from day 4
      (chi2 = 8.49, p < 0.01) onwards. In the absence of hot water or drying, 6/7 of
      these species survived for 16 days, highlighting the importance of good
      biosecurity practice to reduce the risk of accidental spread. In an additional
      experiment the minimum lethal temperature and exposure time in hot water to cause
      100 % mortality in American signal crayfish (Pacifastacus leniusculus), was
      determined to be 5 min at 40  degrees C. Hot water provides a simple, rapid and
      effective method to clean equipment. We recommend that it is advocated in future
      biosecurity awareness campaigns.

PMID- 26316841
TI  - The potential of pale flax as a source of useful genetic variation for cultivated
      flax revealed through molecular diversity and association analyses.
AB  - Pale flax (Linum bienne Mill.) is the wild progenitor of cultivated flax (Linum
      usitatissimum L.) and represents the primary gene pool to broaden its genetic
      base. Here, a collection of 125 pale flax accessions and the Canadian flax core
      collection of 407 accessions were genotyped using 112 genome-wide simple sequence
      repeat markers and phenotyped for nine traits with the aim of conducting
      population structure, molecular diversity and association mapping analyses. The
      combined population structure analysis identified two well-supported major groups
      corresponding to pale and cultivated flax. The L. usitatissimum convar. crepitans
      accessions most closely resembled its wild progenitor, both having dehiscent
      capsules. The unbiased Nei's genetic distance (0.65) confirmed the strong genetic
      differentiation between cultivated and pale flax. Similar levels of genetic
      diversity were observed in both species, albeit 430 (48 %) of pale flax alleles
      were unique, in agreement with their high genetic differentiation. Significant
      associations were identified for seven and four traits in pale and cultivated
      flax, respectively. Favorable alleles with potentially positive effect to improve
      yield through yield components were identified in pale flax. The allelic
      frequencies of markers associated with domestication-related traits such as
      capsular dehiscence indicated directional selection with the most common alleles
      in pale flax being absent or rare in cultivated flax and vice versa. Our results
      demonstrated that pale flax is a potential source of novel variation to improve
      multiple traits in cultivated flax and that association mapping is a suitable
      approach to screening pale flax germplasm to identify favorable quantitative
      trait locus alleles.

PMID- 26316844
TI  - Social Cognition and Epilepsy: Understanding the Neurobiology of Empathy and
      Emotion.

PMID- 26316843
TI  - Seizure and Psychosocial Outcomes of Childhood and Juvenile Onset Generalized
      Epilepsies: Wolf in Sheep's Clothing, or Well-Dressed Wolf?
AB  - Studies of generalized electroclinical syndromes can provide guidance regarding
      long-term seizure, cognitive, and psychosocial outcomes. Childhood absence
      epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, and idiopathic
      generalized epilepsy with generalized tonic-clonic seizures alone are
      electroclinical syndromes typically associated with normal intellect and good
      response to antiseizure medications. However, studies have demonstrated
      significantly poorer psychosocial outcomes than expected for these syndromes,
      regardless of seizure control. Potential causes for this include underlying
      abnormalities in social skills, social stigma, and underlying abnormalities in
      brain development and maturation. 

PMID- 26316845
TI  - Postoperative AED Management - Not So Clear Cut.

PMID- 26316846
TI  - Meta-Analysis Revives Genome-Wide Association Studies in Epilepsy.

PMID- 26316847
TI  - Having Catamenial Epilepsy Equals Fewer Seizures in Pregnancy.

PMID- 26316849
TI  - Tuber-Less Models of Tuberous Sclerosis Still Provide Insights Into Epilepsy.

PMID- 26316848
TI  - Where Have All the Temporal Lobe Epilepsy Surgeries Gone?

PMID- 26316850
TI  - Are Ectopic Neurons a Red Herring in Localizing Seizure Foci?

PMID- 26316851
TI  - A Master Plan for the Epilepsies? Toward a General Theory of Seizure Dynamics.

PMID- 26316852
TI  - Reality EEG: Proving the Similarity between Spontaneous and Induced Seizures.

PMID- 26316853
TI  - Synaptopathies Heat Up: Mutations in STX1B in Fever-Associated Epilepsies.

PMID- 26316854
TI  - Immature Interneurons Create a Lasting Impression.

PMID- 26316855
TI  - Guidelines You Can Sink Your Teeth Into.

PMID- 26316857
TI  - Erratum.

PMID- 26316858
TI  - Consensus Over Individualism: Validation of the ILAE Definition for Drug
      Resistant Epilepsy.

PMID- 26316856
TI  - Evidence-Based Guideline: Management of an Unprovoked First Seizure in Adults:
      Report of the Guideline Development Subcommittee of the American Academy of
      Neurology and the American Epilepsy Society.

PMID- 26316859
TI  - Psychogenic Nonepileptic Seizures: Children Are Not Miniature Adults.

PMID- 26316860
TI  - Phenytoin Hypersensitivity: It's Time for Some Individuality.

PMID- 26316861
TI  - Copy Number Matters in Epilepsy.

PMID- 26316862
TI  - Between the Pulse Generator and the Anterior Thalamic Nucleus: The Light at the
      End of the Tunnel.

PMID- 26316863
TI  - Periodic Assessment of the Use of Continuous EEG Monitoring.

PMID- 26316864
TI  - Women With Epilepsy Are More Likely to Have Suffered Abuse and Are Less Likely to
      Receive Treatment for Depression: How Does This Affect Their Pregnancies?

PMID- 26316865
TI  - Improving Seizure Outcomes After Epilepsy Surgery: Time to Break the "Find and
      Cut" Mold.

PMID- 26316866
TI  - Genetics of Epilepsy in Clinical Practice.
AB  - Genetics should now be part of everyday clinical epilepsy practice. Good data
      exist to provide empiric risks based on epilepsy syndrome diagnosis.
      Investigation of the molecular basis of some epilepsies is now a practical
      clinical task and is of clear value to the patient and family. In some cases,
      specific therapeutic decisions can now be made based on genetic findings, and
      this scenario of precision therapy is likely to increase in the coming years. 

PMID- 26316867
TI  - Clinical Genetic Testing in Epilepsy.
AB  - New technologies for mutation detection in the human genome have greatly
      increased our understanding of epilepsy genetics. Application of genomic
      technologies in the clinical setting allows for more efficient genetic diagnosis
      in some patients; therefore, it is important to understand the types of tests
      available and the types of mutations that can be detected. Making a genetic
      diagnosis improves overall patient care by enhancing prognosis and recurrence
      risk counseling and informing treatment decisions. 

PMID- 26316868
TI  - Autism and Cognition Within Epilepsy: Social Matters.
AB  - The association of epilepsy, autism spectrum disorders (ASD), and intellectual
      disability (ID) is well recognized. There is a wide range of social-cognitive
      deficits that can be identified in epilepsy over the life-span, from ASD in
      infants with an epileptic encephalopathy, to social-cognitive impairments
      affecting social interaction and comprehension in those with normal nonsocial
      cognitive function. Identifying ASD and social-cognitive deficits is an important
      aspect of comprehensive epilepsy care. There are behavioral and educational
      interventions that exist to treat ASD and social-cognitive deficits. These
      behavioral, communication, and educational interventions, in conjunction with
      medications to treat the seizures, should be considered an integral part of the
      comprehensive management of epilepsy throughout the life-span. The following are
      the key points of this review: Autism spectrum disorders and social-cognitive
      deficits are associated with epilepsy throughout the life-span, and
      identification of these deficits is an important part of epilepsy care.Children
      with an epileptic encephalopathy such as infantile spasms are at high risk for
      developing ASD, and the social-cognitive deficits that precede ASD may be
      recognized in the first year of life.In epilepsy, the likelihood of developing
      autism spectrum disorders is highest in those with ID, but there is a wide
      spectrum of manifestations, from ASD in children with epilepsy and ID, to social
      cognitive impairments affecting social interaction and comprehension in those
      with normal nonsocial cognitive function.Implementation of behavioral,
      communication, and educational interventions that exist to treat ASD and social
      cognitive deficits, along with medications to treat the seizures, should be
      considered an important part of the comprehensive management of epilepsy
      throughout the life-span. 

PMID- 26316870
TI  - Abby...Normal? A New Gold Standard for Identifying Normal High Frequency
      Oscillations.

PMID- 26316869
TI  - Autism and Epilepsy: Exploring the Relationship Using Experimental Models.
AB  - The common co-occurrence of autism and epilepsy suggests that certain
      neurobiological mechanisms are shared between these disorders. In particular, the
      profusion of novel genetic mutations being discovered in autism and epilepsy
      points to abnormalities in synapse formation and function that alter the balance
      between neuronal excitation and inhibition. Animal models can be informative in
      sorting out the medical and behavioral complexities in autism and epilepsy and
      the relationship between them. As mechanistic information accrues, it is
      anticipated that mutation- and pathway-specific targeted treatments can be
      developed. 

PMID- 26316871
TI  - Implicating Interneurons: Optogenetic Studies Suggest That Interneurons Are
      Guilty of Contributing to Epileptiform Activity.

PMID- 26316872
TI  - One Mutation Deserves Another in the Quest for Antiepileptogenesis.

PMID- 26316873
TI  - To Arouse Or Not To Arouse: The Cholinergic Question.

PMID- 26316874
TI  - More Than mTOR? Novel Roles for MEK-ERK1/2 and FLNA in Tuberous Sclerosis
      Complex.

PMID- 26316875
TI  - Go Out and Play; Your Brain Needs the Exercise.

PMID- 26316876
TI  - Taking Sides: Physician's Perceptions on the Use of the Wada Test in Epilepsy
      Surgery-Q-PULSE Survey Commentary.
AB  - The recent Q-PULSE Survey compiled by Chad Carlson asked members to place the
      Wada test (bilateral intracarotid amobarbital test) in the context of the current
      practice of epilepsy surgery. Historically, the Wada test has three purposes: to
      lateralize language, to assess the risk of memory loss after epilepsy surgery,
      and to help provide predictive data in localization of the epileptic focus. 

PMID- 26316877
TI  - Phage L5 integrating vectors are present within the Mycobacterial Cell in an
      equilibrium between integrated and excised states.
AB  - Integrating mycobacterial plasmids containing the phage L5 attachment site (attP)
      are able to insert into the mycobacterial chromosome attB site. Plasmids
      containing the attP site and chromosome containing the attB site are present in
      equilibrium between the inserted and the excised states in the presence of the
      phage L5 integrase.

PMID- 26316878
TI  - A Note on Income Effects and Health Care Cost Growth in Medicare.
AB  - This paper sets out a model of technical change and health care cost growth for a
      representative Medicare beneficiary facing a budget constraint. Derivation of an
      explicit expression for health care cost growth shows how technological change
      and preferences, including income effects, affect cost growth. The analysis
      highlights the role of the 76% percent subsidy from current taxpayers to Medicare
      beneficiaries for purchase of health insurance. This subsidy insulates
      beneficiaries from the income effects of cost growth by shifting the costs and
      income effects to taxpayers. Simulations show that over the next 10-20 years,
      income effects will have little effect on cost growth in Medicare.

PMID- 26316879
TI  - On the competition among aerosol number, size and composition in predicting CCN
      variability: a multi-annual field study in an urbanized desert.
AB  - A 2-year data set of measured CCN (cloud condensation nuclei) concentrations at
      0.2 % supersaturation is combined with aerosol size distribution and aerosol
      composition data to probe the effects of aerosol number concentrations, size
      distribution and composition on CCN patterns. Data were collected over a period
      of 2 years (2012-2014) in central Tucson, Arizona: a significant urban area
      surrounded by a sparsely populated desert. Average CCN concentrations are
      typically lowest in spring (233 cm-3), highest in winter (430 cm-3) and have a
      secondary peak during the North American monsoon season (July to September; 372
      cm-3). There is significant variability outside of seasonal patterns, with
      extreme concentrations (1 and 99 % levels) ranging from 56 to 1945 cm-3 as
      measured during the winter, the season with highest variability. Modeled CCN
      concentrations based on fixed chemical composition achieve better closure in
      winter, with size and number alone able to predict 82% of the variance in CCN
      concentration. Changes in aerosol chemical composition are typically aligned with
      changes in size and aerosol number, such that hygroscopicity can be parameterized
      even though it is still variable. In summer, models based on fixed chemical
      composition explain at best only 41% (pre-monsoon) and 36% (monsoon) of the
      variance. This is attributed to the effects of secondary organic aerosol (SOA)
      production, the competition between new particle formation and condensational
      growth, the complex interaction of meteorology, regional and local emissions and
      multi-phase chemistry during the North American monsoon. Chemical composition is
      found to be an important factor for improving predictability in spring and on
      longer timescales in winter. Parameterized models typically exhibit improved
      predictive skill when there are strong relationships between CCN concentrations
      and the prevailing meteorology and dominant aerosol physicochemical processes,
      suggesting that similar findings could be possible in other locations with
      comparable climates and geography.

PMID- 26316881
TI  - Tree component biomass expansion factors and root-to-shoot ratio of Lebombo
      ironwood: measurement uncertainty.
AB  - BACKGROUND: National and regional aboveground biomass (AGB) estimates are
      generally computed based on standing stem volume estimates from forest
      inventories and default biomass expansion factors (BEFs). AGB estimates are
      converted to estimates of belowground biomass (BGB) using default root-to-shoot
      ratios (R/S). Thus, BEFs and R/S are not estimated in ordinary forest
      inventories, which results in uncertainty in estimates of AGB and BGB. Here, we
      measured BEF and R/S values (including uncertainty) for different components of
      Lebombo ironwood (Androstachys johnsonii Prain) trees and assessed their
      dependence on tree size. RESULTS: The BEF values of tree components were
      unrelated or weakly related to tree size, and R/S was independent of tree size.
      BEF values varied from 0.02 for foliage to 1.31 Mg m-3 for whole tree;
      measurement uncertainty (SE) varied from 2.9% for stem BEF to 10.6% for whole
      tree BEF. The belowground, aboveground, and whole-tree BEF-based biomass
      densities were 30 +/- 2.3 (SE = 3.89%), 121 +/- 7.84 (SE = 3.23%), and 151 +/-
      9.87 Mg ha-1(SE = 3.27%), respectively. R/S was 0.24 with an uncertainty of 3.4%.
      CONCLUSIONS: Based on the finding of independence or weak dependence of BEF on
      tree size, we concluded that, for A. johnsonii, constant component BEF values can
      be accurately used within the interval of harvested tree sizes.

PMID- 26316880
TI  - Collagen Mimetic Peptides: Progress Towards Functional Applications.
AB  - Traditionally, collagen mimetic peptides (CMPs) have been used for elucidating
      the structure of the collagen triple helix and the factors responsible for its
      stabilization. The wealth of fundamental knowledge on collagen structure and cell
      extracellular matrix (ECM) interactions accumulated over the past decades has led
      to a recent burst of research exploring the potential of CMPs to recreate the
      higher order assembly and biological function of natural collagens for biomedical
      applications. Although a large portion of such research is still at an early
      stage, the collagen triple helix has become a promising structural motif for
      engineering self-assembled, hierarchical constructs similar to natural tissue
      scaffolds which are expected to exhibit unique or enhanced biological activities.
      This paper reviews recent progress in the field of collagen mimetic peptides that
      bears both direct and indirect implications to engineering collagen-like
      materials for potential biomedical use. Various CMPs and collagen-like proteins
      that mimic either structural or functional characteristics of natural collagens
      are discussed with particular emphasis on providing helpful information to
      bioengineers and biomaterials scientists interested in collagen engineering.

PMID- 26316882
TI  - Identifying nutritional, functional, and quality of life correlates with male
      hypogonadism in advanced cancer patients.
AB  - With the availability of a potential treatment to reverse male hypogonadism (MH),
      the primary aim of this case series study was to determine independent
      relationships between this condition and the nutritional, functional, and quality
      of life characteristics of advanced cancer patients (ACP). Free testosterone
      levels were measured in 100 male patients with advanced lung and gastrointestinal
      (GI) cancer. Routine blood markers of nutrition and inflammation, self-reporting
      questionnaires for symptom, nutrition, and functional status along with handgrip
      dynamometry were assessed for all patients at bedside. Almost half of this cohort
      underwent further assessments (body composition, lower body strength, in depth
      quality of life and fatigue questionnaires) at the McGill Nutrition and
      Performance Laboratory (mnupal.mcgill.ca). Multiple regression analyses were
      performed to identify independent correlations between free testosterone and the
      above measures. Seventy-six percent of patients were diagnosed with MH. Using
      multiple linear regression, low free testosterone (31.2 pmol/L) was independently
      associated with lower albumin (B = -3.8 g/L; 95% confidence interval CI -6.8:
      0.8), muscle strength (-11.7 lbs; -20.4: -3.0) and mass in upper limbs (-0.8 kg; 
      1.4: -0.1), overall performance status (Eastern Cooperative Oncology Group
      Performance Scale, ECOG PS 0.6; 0.1:1.1), cancer-related fatigue (Brief Fatigue
      Inventory, BFI 16.7; 2.0: 31.3), and overall quality of life (MQoL total score 
      1.42; -2.5: -0.3). Thus MH seems to be highly prevalent in ACP, and it is
      independently associated with important nutritional, functional, and quality of
      life characteristics in this patient population. 

PMID- 26316883
TI  - Impact of immunohistochemistry-based molecular subtype on chemosensitivity and
      survival in Hispanic breast cancer patients following neoadjuvant chemotherapy.
AB  - BACKGROUND: Neoadjuvant chemotherapy (NAC) is the standard treatment for patients
      with locally advanced breast cancer, showing improvement in disease-free survival
      (DFS) and overall survival (OS) rates in patients achieving pathological complete
      response (pCR). The relationship between immunohistochemistry-based molecular
      subtyping (IMS), chemo sensitivity and survival is currently a matter of
      interest. We explore this relationship in a Hispanic cohort of breast cancer
      patients treated with NAC. METHODS: A retrospective survival analysis was
      performed on Colombian females with breast cancer treated at Instituto de
      Cancerologia-Clinica Las Americas between January 2009 and December 2011.
      Patients were classified according to immunohistochemistry-based subtyping into
      the following five groups: Luminal A, Luminal B, Luminal B/HER 2+, HER2-enriched,
      and triple-negative breast cancer. Demographic characteristics, recurrence
      pattern, and survival rate were reviewed by bivariate and multivariate analysis.
      RESULTS: A total of 328 patients fulfilled the study's inclusion parameters and
      the distribution of subtypes were as follows: Luminal A: 73 (22.3%), Luminal
      B/HER2-: 110 (33.5%), Luminal B/HER2+: 75 (22.9%), HER2-enriched: 30 (9.1%), and
      triple-negative: 40 (12.2%). The median follow-up was 41 months (interquartile
      range: 31-52). Pathological response to NAC was as follows: complete pathological
      response (pCR) in 28 (8.5%) patients, partial 247 (75.3%); stable disease 47
      (14.3%), and progression 6 (1.8%) patients. The presence of pCR had a significant
      DFS and OS in the entire group (p = 0.01) but subtypes had different DFS in
      Luminal B (p = 0.01) and triple negative (p = 0.02) and also OS in Luminal B (p =
      0.01) and triple negative (p = 0.01). CONCLUSIONS: pCR is associated with an
      improved overall survival and disease-free survival rates in this group of
      Hispanics patients. Advanced stages, Luminal B subtypes, triple-negative tumours
      and non-pCR showed lower DFS.

PMID- 26316884
TI  - Phase II trial of metformin and paclitaxel for patients with gemcitabine
      refractory advanced adenocarcinoma of the pancreas.
AB  - BACKGROUND: In patients with adenocarcinoma of the pancreas, there are no
      standard second-line regimens. Many pre-clinical studies have shown that
      metformin alone or when combined with paclitaxel has antitumour effects on this
      tumour. We have tested here the combination of paclitaxel and metformin for
      patients with gemcitabine-refractory pancreatic cancer. METHODS: An uncontrolled
      phase II trial was carried out based on a two-stage Simon's design, with
      metformin and paclitaxel for patients with locally advanced or metastatic
      pancreatic cancer whose disease had progressed during first line treatment with a
      gemcitabine-based regimen. The primary endpoint was the disease control rate at
      eight weeks as per response evaluation criteria in solid tumours (RECIST) 1.1.
      Patients received paclitaxel 80 mg/m(2) weekly for three weeks every 28 days and
      metformin 850 mg p.o. t.i.d. continuously until progression or intolerance state
      was reached. RESULTS: Twenty patients were enrolled from July 2011 to January
      2014: N = 6 (31.6%) achieved the primary endpoint, with all presenting stable
      disease. Median overall survival (OS) was 128 days (range 17-697) and the median
      progression free survival (PFS) was 44 days (range 14-210). Eight patients (40%)
      presented treatment-related G3-4 toxicities with the most common one being
      diarrhoea. CONCLUSIONS: Despite the encouraging pre-clinical evidence of the
      antitumour activity of metformin in adenocarcinoma of the pancreas, the primary
      endpoint of the disease control rate was not met. Besides, the treatment
      combination was poorly tolerated and could not be studied further. This study
      highlights the importance of performing clinical trials to reassure preclinical
      or observational data.

PMID- 26316885
TI  - Highlights from the 2015 WIN Symposium: novel targets, innovative agents, and
      advanced technologies-a WINning strategy?
AB  - The worldwide innovative networking (WIN) consortium comprises a global alliance
      of 28 academic and clinical cancer centres, 11 pharmaceutical and technology
      companies and five charitable or health payer organisations. Since its inception
      the consortium has striven to provide a forum for all of its members to network,
      share information and experience, and perform clinical trials with the
      overarching goal of advancing the care of patients with cancer through the use of
      precision medicine. The annual 2-day WIN Symposium is the most visible output of
      the consortium and provides an opportunity for around 400 experts and other
      delegates to meet and discuss the latest research and initiatives in personalised
      cancer medicine. The seventh WIN Symposium, held in Paris, France, 29-30 June
      2015, consisted of nine plenary and eight poster sessions that covered the
      overarching theme of novel targets, innovative agents, and advanced technologies
      being a winning strategy. Highlights included discussions of immune mechanisms
      and ways to target the cancer immunome and systems biology approaches to
      supporting personalised cancer. The latest data from the BATTLE-2 and WINther
      trials were discussed, and round table discussions were held that focused on how
      best to design the next generation of clinical trials, which included SPRING,
      SUMMER, and BOOSTER being initiated by the WIN Consortium. 

PMID- 26316886
TI  - Conference report from the 2015 OECI Oncology Days, Portugal, 22-24 June-tumour
      heterogeneity and next generation sequencing: morphology and technology.
AB  - Tumour heterogeneity was the topic of the 'Oncology Days' series held at the 2015
      OECI conference in which experts within the field provided an update on tumour
      heterogeneity and its relevance in the clinical setting. Here we present a
      summary of the presentations from the two major sessions of the meeting: clonal
      heterogeneity and phenotypic heterogeneity. 

PMID- 26316887
TI  - Diagnostic value of SOX-10 immunohistochemical staining for the detection of
      uveal melanoma.
AB  - OBJECTIVES: SOX-10 has been shown to be a sensitive marker of cutaneous melanoma.
      This study aimed to evaluate Sox-10 expression in uveal melanoma. METHODS: A
      total of 40 tissue blocks of enucleated eyes with uveal melanoma were cut and
      stained using an anti-SOX-10 mouse monoclonal antibody and HMB-45 antibody.
      RESULTS: SOX-10 showed exclusive nuclear positivity in 100% of the uveal melanoma
      cases (38/38). HMB-45 showed cytoplasmic positivity in 97.3 (37/38). Positivity
      for SOX-10 was also noted in the inner and outer nuclear layers of the retina in
      78% of the enucleated eyes. CONCLUSIONS: SOX-10 expression proved to be the most
      sensitive marker for uveal melanoma, and therefore, we propose a modified panel
      for the diagnosis of uveal melanoma that includes both SOX-10 and HMB-45. The
      observation of distinct, diffuse nuclear SOX-10 expression in retinal inner and
      outer nuclear layers is a finding that warrants further investigation as a marker
      for retinoblastoma.

PMID- 26316888
TI  - Carbonic Anhydrase XII as an Independent Prognostic Factor in Advanced Esophageal
      Squamous Cell Carcinoma.
AB  - BACKGROUND: Although recent studies described important roles for carbonic
      anhydrase (CA) XII in epithelial carcinogenesis and tumor behavior, a consensus
      has not yet been reached regarding its clinicopathological significance in
      esophageal squamous cell carcinoma (ESCC). In the present study, we investigated
      its prognostic significance in ESCC. MATERIALS AND METHODS: An
      immunohistochemical analysis was performed on 70 primary tumor samples obtained
      from ESCC patients who underwent esophagectomy, and the relationships between the
      expression of CA XII and various clinicopathological features or prognosis were
      analyzed. RESULTS: Immunohistochemical staining showed that CA XII was primarily
      found in the cell membranes of carcinoma cells. Although the expression of CA XII
      was related to the pT category, it had no prognostic impact. We then examined the
      expression of CA XII according to the pT category. In pT2-3 ESCC, the 3-year
      survival rate of patients with the high grade expression of CA XII (29.1 %) was
      significantly lower than that of patients with the low grade expression of CA XII
      (70.3 %). Furthermore, a multivariate analysis demonstrated that the expression
      of CA XII was one of the most important independent prognostic factors following
      radical esophagectomy in pT2-3 ESCC. CONCLUSION: These results suggest that the
      expression of CA XII may be a valuable prognostic factor for patients with
      advanced ESCC. The results of the present study provide an insight into the role
      of CA XII as a biomarker in ESCC.

PMID- 26316889
TI  - Transcriptomic and Functional Pathway Analysis of Human Cervical Carcinoma Cancer
      Cells Response to Microtubule Inhibitor.
AB  - BACKGROUND: There clearly is a need for effective chemotherapy for early-stage,
      high-risk patients with human cervical carcinoma. Vinblastine (VBL) is a key
      microtubule inhibitor, but unproven in its mechanisms as an important antitumor
      agent in cervical carcinoma. METHODS: We selected the concentration of
      vinblastine inducing 30% cell death for analyses assessing the DNA content, gene
      expression and transcriptional gene regulation of VBL-treated KB-3 cells.
      RESULTS: Transcriptomic and hierarchical clustering analysis demonstrated that
      treatment of KB-3 cells with VBL altered the expression of a diverse group of
      genes with G2/M arrest, which regulated by four oncogenic or tumor suppresser
      transcription factors (AP1, NFKB1, RELA, and TP53). Functional pathway analysis
      revealed the disease response to the biological effects of vinblastine in
      cervical carcinoma chemotherapy including protein ubiquitination pathway, RhoGDI
      signaling, integrin signaling, agranulocyte adhesion and biapedesis, and actin
      nucleation pathways. Northern blots also confirmed that KRT-7, FN14, IER3, and
      ID1 were deregulated in VBL-treated KB-3 cells. CONCLUSION: Transcriptional time
      series profiles and a functional pathway analysis of VBL-treated KB-3 cells will
      provide a new strategy for improving microtubule inhibitor chemotherapy for
      cervical carcinoma.

PMID- 26316891
TI  - Loss of IRF8 Inhibits the Growth of Diffuse Large B-cell Lymphoma.
AB  - IRF8 is a transcription factor with a critical role in B lymphocyte development
      and functions. Its role in human diffuse large B-cell lymphoma (DLBCL), however,
      remained elusive. In this study, using shRNA-mediated knockdown of IRF8
      expression, we found that the loss of IRF8 significantly reduced the
      proliferation of DLBCL cells (P<0.05). Mechanistically, decreasing the levels of
      IRF8 led to a suppression of the phosphorylation of p38 and ERK, molecules
      critical for B cell proliferation. Furthermore, using a xenograft lymphoma mouse
      model, we found that the loss of IRF8 significantly inhibited the growth of
      lymphomas in vivo (P<0.05). Immunohistochemical analysis of human DLBCL tissues
      revealed that the levels of IRF8 were significantly greater in non-germinal
      center B-cell-like (non-GCB) subtype than that in GCB subtype (P<0.05). Analysis
      of public available data also suggested that the expression levels of IRF8 mRNA
      in human DLBCL tissues were inversely correlated with patients' overall survival
      time. Taken together, this study suggested that IRF8 may play an oncogenic role
      in human DLBCL by promoting cell proliferation. 

PMID- 26316892
TI  - Interleukin 37 Expression Inhibits STAT3 to Suppress the Proliferation and
      Invasion of Human Cervical Cancer Cells.
AB  - OBJECTIVES: The most recently discovered cytokine interleukin 37 (IL-37) received
      growing attention. Its function on tumor is largely unknown. Here, we
      investigated the biological function of IL-37 on cervical cancer (CC). Materials
      and methods : HPV(+) Hela cells and HPV(-) C33A cells were used. RT-qPCR was
      performed to detect the transcription of IL-37, STAT3, TNF-alphaand IL-1beta.
      Western blotting was used for protein detection. CCK-8 assay and transwell assay
      were employed for cell proliferation and invasion detection, respectively.
      Results : Successful gene transfection of IL-37 suppressed the proliferation and
      invasion of CC. Interestingly, IL-37 showed higher anticancer ability in HPV(+)
      Hela cells than that in HPV(-) C33A cells. Then, the molecular mechanism of IL-37
      anticancer was explored. Firstly, we found that IL-37 inhibited STAT3 expression
      at both mRNA and protein levels. IL-37 also down regulated the phosphorylation of
      STAT3. Secondly, blockage of STAT3 using siRNAs reduced significantly the ability
      of IL-37 to suppress cell proliferation and invasion. Thirdly, STAT3 knockdown
      reduced markedly the inhibition of IL-37 on the transcription of tumor-derived
      TNF-alpha and IL-1beta, indicating the contribution of STAT3 for the cancer
      associated antiinflammation of IL-37. Finally, STAT3 up regulation restored the
      ability of cell proliferation, cell invasion and the expression of inflammatory
      cytokines, TNF-alpha and IL-1beta. Conclusions : IL-37 suppressed cell
      proliferation and invasion of CC and STAT3 is involved in this process. Thus, IL
      37 emerges as a new anticancer cytokine for CC. This study demonstrated a new
      biological function of IL-37 and offered a potential molecule for CC treatment.

PMID- 26316893
TI  - Prognostic Impact of ABO Blood Group on the Survival in Patients with Ovarian
      Cancer.
AB  - PURPOSE: The impact of ABO blood group on the survival of patients with ovarian
      cancer remains uncertain. The aim of this study was to evaluate the prognostic
      value of the ABO blood group in ovarian cancer patients. METHODS: 256 ovarian
      cancer patients who received a cytoreductive surgery were retrospectively
      reviewed. The prognostic impact of the ABO blood group with respect to overall
      survival (OS) was analyzed. RESULTS: The median follow-up time was 57 months and
      the 5-year OS was 70.1%. The 5-year OS were 55.0%, 83.3%, 82.5%, and 70.0% in
      patients with A, B, AB, and O blood type, respectively (p = 0.003). Patients with
      blood type A had a poorer 5-year OS than patients with blood type non-A (55.0%
      vs. 75.0%, p = 0.001), especially in patients with age > 50 years (40.0% vs.
      62.5%, p = 0.004). Univariate Cox analyses showed that blood type A was
      significantly associated with OS than those with non-A types (hazard ratio (HR)
      2.210, 95% confidence interval (CI) 1.373-3.557, p = 0.001). Blood type A
      remained an independent prognostic factor for OS than those with non-A blood
      types in multivariate analyses (HR 2.235, 95% CI 1.360-3.674, p = 0.002).
      CONCLUSION: ABO blood group is associated with survival in patients with ovarian
      cancer, patients with blood type A had a significantly worse OS than patients
      with non-A blood types, especially in patients with age > 50 years.

PMID- 26316890
TI  - Role of Chemokines in Non-Small Cell Lung Cancer: Angiogenesis and Inflammation.
AB  - Non-small cell lung cancer (NSCLC) is one of the most common types of aggressive
      cancer. The tumor tissue, which shows an active angiogenesis, is composed of
      neoplastic and stromal cells, and an abundant inflammatory infiltrate.
      Angiogenesis is important to support tumor growth, while infiltrating cells
      contribute to the tumor microenvironment through the secretion of growth factors,
      cytokines and chemokines, important molecules in the progression of the disease.
      Chemokines are important in development, activation of the immune response, and
      physiological angiogenesis. Chemokines have emerged as important regulators in
      the pathophysiology of cancer. These molecules are involved in the
      angiogenesis/angiostasis balance and in the recruitment of tumor infiltrating
      hematopoietic cells. In addition, chemokines promote tumor cell survival, as well
      as the directing and establishment of tumor cells to metastasis sites. The
      findings summarized here emphasize the central role of chemokines as modulators
      of tumor angiogenesis and their potential role as therapeutic targets in the
      inflammatory process of NSCLC angiogenesis. 

PMID- 26316894
TI  - To Target or Not to Target: Active vs. Passive Tumor Homing of Filamentous
      Nanoparticles Based on Potato virus X.
AB  - Nanoparticles are promising platforms for the diagnosis and treatment of cancer.
      Diverse classes and shapes of materials have been investigated to establish
      design principles that achieve the effective partitioning of medical cargos
      between tumors and healthy tissues. Molecular targeting strategies combined with
      specific nanoparticle shapes confer tissue-specificity on the carriers, allowing
      the cell-specific delivery of cargos. We recently developed a filamentous
      platform technology in which the plant virus Potato virus X (PVX) was used as a
      scaffold. These particles are flexible 515 * 13 nm filaments that encourage
      passive tumor homing. Here we sought to advance the PVX platform by including a
      molecular targeting strategy based on cyclic RGD peptides, which specifically
      bind to integrins upregulated on tumor cells, neovasculature, and metastatic
      sites. Although the RGD-targeted filaments outperformed the PEGylated stealth
      filaments in vitro, enhanced tumor cell targeting did not translate into improved
      tumor homing in vivo in mouse tumor models. The RGD-PVX and PEG-PVX filaments
      showed contrasting biodistribution profiles. Both formulations were cleared by
      the liver and spleen, but only the stealth filaments accumulated in tumors,
      whereas the RGD-targeted filaments were sequestered in the lungs. These results
      provide insight into the design principles for virus-based nanoparticles that
      promote the delivery of medical cargos to the appropriate cell types.

PMID- 26316895
TI  - Investigating the specific uptake of EGF-conjugated nanoparticles in lung cancer
      cells using fluorescence imaging.
AB  - Targeted nanoparticles have the potential to deliver a large drug payload
      specifically to cancer cells. Targeting requires that a ligand on the
      nanoparticle surface interact with a specific membrane receptor on target cells.
      However, the contribution of the targeting ligand to nanoparticle delivery is
      often influenced by non-specific nanoparticle uptake or secondary targeting
      mechanisms. In this study, we investigate the epidermal growth factor (EGF)
      receptor-targeting specificity of a nanoparticle by dual-color fluorescent
      labeling. The targeted nanoparticle was a fluorescently labeled, EGF-conjugated
      HDL-like peptide-phospholipid scaffold (HPPS) and the cell lines expressed EGF
      receptor linked with green fluorescent protein (EGFR-GFP). Using LDLA7 cells
      partially expressing EGFR-GFP, fluorescence imaging demonstrated the co
      internalization of EGFR-GFP and EGF-HPPS, thus validating its targeting
      specificity. Furthermore, specific EGFR-mediated uptake of the EGF-HPPS
      nanoparticle was confirmed using human non-small cell lung cancer A549 cells.
      Subsequent confocal microscopy and flow cytometry studies delineated how
      secondary targeting mechanisms affected the EGFR targeting. Together, this study
      confirms the EGFR targeting of EGF-HPPS in lung cancer cells and provides insight
      on the potential influence of unintended targets on the desired ligand-receptor
      interaction.

PMID- 26316896
TI  - Facile synthesis of biocompatible gold nanoparticles from Vites vinefera and its
      cellular internalization against HBL-100 cells.
AB  - The remarkable health benefits of the chemical cocktails occluded within Vites
      vinefera (grapes) have been broadly used as dietary supplements and as natural
      pharmaceuticals in the treatment of various diseases including human cancer.
      Current discovery demonstrates the rapid formation of gold nanoparticles with the
      phytochemicals present in grapes, which serve a dual role as synergistic reducing
      agents to reduce gold salts into gold nanoparticles and also as stabilizers to
      provide a robust coating on the gold nanoparticles in a single step. Furthermore,
      the grape-generated gold nanoparticles (GAuNPs), have demonstrated remarkable in
      vitro stability on specific functionalization with peptides (GSH) and thiol
      containing compounds (lipoic acid) followed by the induction of cell-specific
      response. In addition, the grape-generated gold nanoparticles (GAuNPs, GSH
      GAuNPs, LA-GAuNPs) have demonstrated remarkable affinity towards human breast
      cancer cells (HBL-100) in the present study. These studies thus signified the
      cellular internalization of GAuNPs and its conjugates by transmission electron
      microscopy through endocytosis into cancer cells. Notably, at higher
      concentration of gold nanoparticles conjugate, there was an asymmetric
      accumulation of gold nanoparticles in the periphery of the cell nucleus of the
      HBL-100 cells which was confirmed by fluorescence microscopy. Other than gold
      salts, no "manmade" chemicals are used in this truly biogenic, green
      nanotechnological process which thereby paves the way for outstanding opening for
      their application in molecular imaging and cancer therapy.

PMID- 26316897
TI  - Development of in vitro gene delivery system using ORMOSIL nanoparticle: Analysis
      of p53 gene expression in cultured breast cancer cell (MCF-7).
AB  - This article reports on the application of organically modified silica (ORMOSIL)
      nanoparticles as an efficient in vitro gene delivery system in the recent years.
      Based on that prime objective, the present study addresses the possible ways to
      reduce cancers incidence at cellular level. In this context, ORMOSIL
      nanoparticles had been synthesized and incubated along with pCMV-Myc (3.8 kb)
      plasmid vector construct carrying p53gene, and transfected into the breast cancer
      cell line MCF-7 cells. Western blot analysis showed that the p53 protein was
      significantly expressed in breast cancer cell upon transfection. The confocal and
      electron microscopic studies further confirmed that the nanoparticles were
      accumulated in the cytoplasm and the nucleus of the cancer cells transfected with
      p53 gene. Interesting agarose gel electrophoresis studies revealed that the
      nanoparticles efficiently complex with pCMV-Myc vector. The anti-cancer
      properties of p53 were demonstrated by assessing the cell survival and growth
      rate which showed a positive linear correlation in cancer cells. Whereas, the
      growth rate was significantly reduced in ORMOSIL/p53/pCMV-Myc transfected breast
      cancer cells compared to the growth rate of non-transfected cells. The results of
      this approach using ORMOSIL nanoparticles as a non-viral gene delivery platform
      have a promising future for use as effective transfection agent for therapeutic
      manipulation of cancer cells and targeted cancer gene therapy in vivo.

PMID- 26316898
TI  - Size-dependent cellular toxicity and uptake of commercial colloidal gold
      nanoparticles in DU-145 cells.
AB  - Urinary tract infection (UTI) is a predominant condition in prostate cancer
      patients. Escherichia coli ORN178 (EC-178) is the uropathogen that causes
      recurrent infection by binding specifically to adhesins of prostate cancer cells
      (DU-145 cells). Gold nanoparticles (GNPs) have been used in biodiagnosis of
      pathogens. In this study, we have investigated the binding time of EC-178 to DU
      145 cells, the cytotoxicity and uptake of plain and mannose functionalized and 20
      and 200 nm GNPs (d-mannan (Mn)-GNPs). We also investigated the protein corona of
      GNPs when incubated with fetal bovine serum to study the protein corona which
      decides the biological fate of the GNPs. It was seen that EC-178 binds and is
      inside the DU-145 cells by 3 h of incubation period. Plain 20 nm GNPs decrease
      the percentage of viable cells in 48 and 72 h in log and lag phase of DU-145
      cells. It was also observed that the Mn-GNPs were taken up by the DU-145 cells
      significantly more than the plain GNPs. Protein corona was observed when GNPs
      were incubated with fetal bovine serum which was confirmed by dynamic light
      scattering measurements and SDS-PAGE gel.

PMID- 26316899
TI  - Development of A Physical Windkessel Module to Re-Create In-Vivo Vascular Flow
      Impedance for In-Vitro Experiments.
AB  - PURPOSE: To create and characterize a physical Windkessel module that can provide
      realistic and predictable vascular impedances for in-vitro flow experiments used
      for computational fluid dynamics validation, and other investigations of the
      cardiovascular system and medical devices. METHODS: We developed practical design
      and manufacturing methods for constructing flow resistance and capacitance units.
      Using these units we assembled a Windkessel impedance module and defined its
      corresponding analytical model incorporating an inductance to account for fluid
      momentum. We tested various resistance units and Windkessel modules using a flow
      system, and compared experimental measurements to analytical predictions of
      pressure, flow, and impedance. RESULTS: The resistance modules exhibited stable
      resistance values over wide ranges of flow rates. The resistance value variations
      of any particular resistor are typically within 5% across the range of flow that
      it is expected to accommodate under physiologic flow conditions. In the
      Windkessel impedance modules, the measured flow and pressure waveforms agreed
      very favorably with the analytical calculations for four different flow
      conditions used to test each module. The shapes and magnitudes of the impedance
      modulus and phase agree well between experiment and theoretical values, and also
      with those measured in-vivo in previous studies. CONCLUSIONS: The Windkessel
      impedance module we developed can be used as a practical tool to provide
      realistic vascular impedance for in-vitro cardiovascular studies. Upon proper
      characterization of the impedance module, its analytical model can accurately
      predict its measured behavior under different flow conditions.

PMID- 26316900
TI  - Language Evolution: Why Hockett's Design Features are a Non-Starter.
AB  - The set of design features developed by Charles Hockett in the 1950s and 1960s
      remains probably the most influential means of juxtaposing animal communication
      with human language. However, the general theoretical perspective of Hockett is
      largely incompatible with that of modern language evolution research.
      Consequently, we argue that his classificatory system-while useful for some
      descriptive purposes-is of very limited use as a theoretical framework for
      evolutionary linguistics. We see this incompatibility as related to the ontology
      of language, i.e. deriving from Hockett's interest in language as a product
      rather than a suite of sensorimotor, cognitive and social abilities that enable
      the use but also acquisition of language by biological creatures (the faculty of
      language). After a reconstruction of Hockett's views on design features, we raise
      two criticisms: focus on the means at the expense of content and focus on the
      code itself rather than the cognitive abilities of its users. Finally, referring
      to empirical data, we illustrate some of the problems resulting from Hockett's
      approach by addressing three specific points-namely arbitrariness and
      semanticity, cultural transmission, and displacement-and show how the change of
      perspective allows to overcome those difficulties.

PMID- 26316902
TI  - The evolution of the CUA.

PMID- 26316901
TI  - Getting started with ambulatory PCNL: A CanMEDS perspective.

PMID- 26316903
TI  - [Not Available].

PMID- 26316904
TI  - The workup and management of azoospermic males.

PMID- 26316905
TI  - Predictors of referral for neoadjuvant chemotherapy prior to radical cystectomy
      for muscle-invasive bladder cancer and changes in practice over time.
AB  - INTRODUCTION: In patients with non-metastatic muscle-invasive bladder cancer
      (MIBC) fit for curative therapy, a multidisciplinary approach consisting is
      recommended. This approach includes local treatment (usually radical cystectomy),
      ideally combined with neoadjuvant chemotherapy (NACT). Despite a survival benefit
      with NACT, uptake remains low. We assessed NACT consultation in Alberta and
      examined associative factors, as well as the relationship to survival. METHODS:
      Patients with MIBC were identified through the Alberta Cancer Registry.
      Demographic and clinicopathologic information was collected from electronic
      medical records between 2007 and 2011. In addition to descriptive statistics,
      logistic regression was used to determine factors associated with receiving NACT
      consultation. Overall survival was described using a Kaplan-Meier estimate.
      RESULTS: Of the 315 radical cystectomy patients, 140 (45.1%, 95% confidence
      interval [CI] 39.5, 50.8) received NACT consultation. Patients >=80 years (odds
      ratio [OR] 0.21, 95% CI 0.08, 0.57, p = 0.002) and those treated in Calgary (OR
      0.11, 95% CI 0.05, 0.25, p < 0.001) were less likely to receive NACT
      consultation. The rate of NACT consultation increased steadily from 2007 to 2011
      (OR 1.23, 95% CI 1.04, 1.45 per year of diagnosis, p = 0.018). After a median
      follow-up of 28.1 months (range: 14.6-50.3), median survival was 54.7 months for
      patients who received NACT consultation versus 31.2 months for those who did not
      (p = 0.030). CONCLUSIONS: NACT consultation in patients with MIBC undergoing
      radical cystectomy has improved over time; however, regional differences
      underscore the need for a standardized approach to NACT consultation, including
      common referral mechanisms.

PMID- 26316906
TI  - Economic evaluation of sacral neuromodulation in overactive bladder: A Canadian
      perspective.
AB  - INTRODUCTION: Refractory overactive bladder (OAB) with urge incontinence is an
      underdiagnosed condition with substantial burden on the healthcare system and
      diminished patient's quality-of-life. Many patients will fail conservative
      treatment with optimized medical-therapy (OMT) and may benefit from minimally
      invasive procedures, including sacral-neuromodulation (SNM) or botulinum-toxin
      (BonT-A). The goal of this study was to estimate the cost-efectiveness of SNM vs.
      OMT and BonT-A as important parameters from coverage and access to a therapy.
      METHODS: A Markov model with Monte-Carlo simulation was used to assess the
      incremental cost effectiveness ratio (ICER) of SNM vs. BonT-A and OMT both in
      deterministic and probabilistic analysis from a provincial payer perspective over
      a 10-year time horizon with 9-month Markov-cycles. Clinical data, healthcare
      resource utilization, and utility scores were acquired from recent publications
      and an expert panel of 7 surgeons. Cost data (2014-Dollars) were derived from
      provincial health insurance policy, drug benefit formulary, and hospital data.
      All cost and outcomes were discounted at a 3% rate. RESULTS: The annual (year 1
      10) incremental quality-adjusted life years for SNM vs. BonT-A was 0.05 to 0.51
      and SNM vs. OMT was 0.19 to 1.76. The annual incremental cost of SNM vs. BonT-A
      was $7237 in year 1 and -$9402 in year 10 and was between $8878 and -$11 447 vs.
      OMT. In the base-case deterministic analysis, the ICER for SNM vs. BonT-A and OMT
      were within the acceptable range ($44 837 and $15 130, respectively) at the
      second year of therapy, and SNM was dominant in consequent years. In the base
      case analysis the probability of ICER being below the acceptability curve
      (willingness-to-pay $50 000) was >99% for SNM vs. BonT-A at year 3 and >95% for
      OMT at year 2. CONCLUSION: SNM is a cost-effective treatment option to manage
      patients with refractory OAB when compared to either BonT-A or OMT. From a
      Canadian payers' perspective, SNM may be considered a first-line treatment option
      in management of patients with OAB with superior long-term outcomes. Similar to
      all economic analysis, this study has limitations which are based on the
      assumptions of the used model.

PMID- 26316907
TI  - Holmium laser transurethral incision of the prostate: Can prostate size predict
      the long-term outcome?
AB  - INTRODUCTION: We determine the impact of prostate size on the long-term outcome
      of holmium laser transurethral incision of the prostate (Ho-TUIP) for bladder
      outlet obstruction (BOO) secondary to benign prostate enlargement (BPE). METHODS:
      A retrospective review of prospectively collected data was performed for patients
      undergoing Ho-TUIP by a single surgeon for patients presenting with lower urinary
      tract symptoms (LUTS) secondary to BOO. Patients were stratified into 2 groups:
      Group 1 included patients with prostate <=30 cc and Group 2 included patients
      with prostate >30 cc. Demographic, operative and follow-up data were recorded and
      analyzed. In addition, intraoperative and long-term adverse events were included.
      RESULTS: In total, 82 patients underwent surgery between March 1998 and March
      2013, including 9 (11%) reoperated patients. Only prostate size independently
      predicted reoperation after Ho-TUIP (adjusted odds ratio [aOR], 95% confidence
      interval [CI] 7.12 [2.92-9.14], p = 0.01). The receiver operating characteristic
      (ROC) analysis showed an optimal cutoff value of prostate volume of 29 cc to
      characterize long-term reoperation after TUIP, with area under the curve (AUC) of
      0.96, sensitivity of 89.7 and specificity of 88.9. Group 1 included 51 patients
      and Group 2 included 31 patients. The international prostate symptoms score
      (IPSS) and peak flow rate (Qmax) significantly improved in both groups at
      different follow-up points. At the 12-month follow-up, the percent change in IPSS
      and Qmax were comparable between both groups. However, after 12 months, the
      degree of improvement in all voiding parameters was significantly higher in Group
      1 (p < 0.001 at all points of follow-up). After a median follow-up of 5.3 years
      (range: 1-13), both groups had comparable early and late adverse events with
      significantly higher reoperation rate in Group 2 (3.9% vs. 22.6%, p = 0.02).
      Overall retrograde ejaculation was detected in 25.6% of sexually active men and
      it was comparable between both groups (23.5% vs. 29%, p = 0.61). On multivariable
      analysis, patients with prostate volume >30 cc were associated with significantly
      higher reoperation for BOO (aOR 95% CI 5.72 [2.83-8.14], p = 0.02), significantly
      higher IPSS (aOR 1.72), higher quality of life index (aOR 1.72) and lower Qmax
      (aOR 0.28). CONCLUSION: Ho-TUIP is a durable, safe and efficient treatment of BOO
      secondary to a small-sized prostate. The long-term outcome could be improved and
      the re-operation rate could be minimized with appropriate selection of cases,
      with prostate glands no bigger than 30 cc.

PMID- 26316908
TI  - Let's not forget about TUIP: A highly underutilized, minimally-invasive and
      durable technique for men with <30 g prostates.

PMID- 26316909
TI  - Leisure time physical activity, smoking and risk of recent symptomatic
      urolithiasis: Survey of stone clinic patients.
AB  - INTRODUCTION: We explore relationships between selected lifestyle factors and
      recent (<=6 months) symptomatic urolithiasis (RSU). METHODS: Surveys querying
      socio-demographic, medical history, physical activity, diet and smoking were
      administered to a convenience sample of stone clinic patients at a tertiary care
      hospital. Leisure time physical activity (LTPA) was assessed with the
      International Physical Activity Questionnaire (long form). Multivariate logistic
      regression was used to identify associations between risk factors and RSU.
      RESULTS: Of the 163 participants, most were male (64%) and white (78%), with a
      mean (standard deviation) age of 56.3 (14.2) years. The mean body mass index
      (BMI) was 27.3 (5.4) kg/m(2) and 57 (35%) patients reported RSU. No significant
      (p < 0.05) differences were observed between participants with and without RSU in
      age, sex, ethnicity, BMI, or diet. Of the cohort, 52 (35%) participants met
      physical activity guidelines for walking (29%), moderate (27%) or vigorous
      activity (29%). LTPA did not differ significantly by RSU status. Compared to
      those without RSU, participants with RSU had higher rates of smoking (7% vs. 21%,
      p = 0.02 and had 8.5 (95% confidence interval 2.2-32.2) times the odds of being
      current smokers after controlling for sex, diet, and LTPA. CONCLUSIONS: Physical
      inactivity and smoking are common among stone clinic patients, though LPTA was
      not associated with RSU. Study limitations include its small sample size,
      selection bias, and reliance on self-reported RSU (recall bias). In addition,
      participants may have already been following dietary recommendations to prevent
      urolithiasis recurrence. Nonetheless, current smoking was a potent predictor of
      RSU. When desired, smokers should be referred for smoking cessation.

PMID- 26316910
TI  - Correlating stone disease and smoking.

PMID- 26316911
TI  - Bone metastases affect prognosis but not effectiveness of third-line targeted
      therapies in patients with metastatic renal cell carcinoma.
AB  - INTRODUCTION: Treatment of metastatic renal cell carcinoma (mRCC) has improved
      with the use of targeted therapies, but bone metastases continue to be negative
      prognostic factor. METHODS: Patients with mRCC treated with everolimus (EV) or
      sorafenib (SO) after two previous lines of targeted therapies were included in
      the analysis. Overall survival (OS) and progression-free survival (PFS) were
      assessed based on the presence of bone metastases and type of therapy; they were
      also adjusted based on prognostic criteria. RESULTS: Of the 233 patients with
      mRCC, 76 had bone metastases. Of the 233 patients, EV and SO were administered in
      143 and 90 patients, respectively. Median OS was 10.4 months in patients with BMs
      and 17.4 months in patients without bone metastases (p = 0.002). EV decreased the
      risk of death by 18% compared to SO (adjusted hazard ratio [HR] 0.82, 95%
      confidence interval [CI] 0.74-0.91; p < 0.001), with comparable effects in
      patients with or without bone metastases. In the same manner, EV decreased the
      risk of progression by 12% compared to SO (adjusted HR 0.88, 95% CI 0.82-0.96; p
      = 0.002), but this difference was not significant in patients without bone
      metastases. The major limitations of the study are its retrospective nature, the
      heterogeneity of the methods to detect bone metastases, and the lack of data
      about patients treated with bisphosphonates. CONCLUSIONS: The relative benefit of
      targeted therapies in mRCC is not affected by the presence of bone metastases,
      but patients without bone metastases have longer response to therapy and overall
      survival.

PMID- 26316912
TI  - Third-line treatment in metastatic renal cell carcinoma and bone metastases.

PMID- 26316913
TI  - Is there a gender effect in bladder cancer? A population-based study of practice
      and outcomes.
AB  - INTRODUCTION: The incidence of bladder cancer varies by gender. Whether
      differences exist between women and men in extent of disease, treatment, and
      outcome is not well-described. We evaluate gender differences in bladder cancer
      using a population-based cohort. METHODS: Electronic records of treatment were
      linked to the population-based Ontario Cancer Registry to identify all patients
      with bladder cancer treated with cystectomy or radical radiotherapy (RT) in
      Ontario between 1994 and 2008. We compare extent of disease at time of
      cystectomy, treatment, and outcomes between women and men. RESULTS: In total,
      5259 patients with bladder cancer were treated with cystectomy or radical RT; of
      these, 25% (n = 1296) were women. There was no gender difference in the
      proportion of patients treated with cystectomy (75% of women [974/1296], 73% of
      men [2905/3963], p = 0.189). At the time of cystectomy, women were more likely to
      have muscle-invasive disease (86% [836/974] vs. 80% [2335/2905], p < 0.001), but
      less likely to have lymph nodes dissected (68% [664/974] vs. 76% [2210/2905], p <
      0.001]. Among the 2944 patients with muscle-invasive urothelial carcinoma treated
      with cystectomy, use of neoadjuvant (5% vs. 4%, p = 0.419) and adjuvant
      chemotherapy (18% vs. 20%, p = 0.190) did not differ significantly between
      genders. Five-year cancer-specific survival and overall survival of the full
      cohort did not differ between women and men (38% vs. 39%, p = 0.522; 33% vs. 33%,
      p = 0.795). CONCLUSIONS: This population-based cohort did not demonstrate any
      substantial differences in extent of disease, treatment, or outcome between women
      and men treated with cystectomy or radical RT for bladder cancer.

PMID- 26316914
TI  - Stereotactic body radiotherapy for the treatment of medically inoperable primary
      renal cell carcinoma: Current evidence and future directions.
AB  - The incidence of renal cell carcinoma (RCC) is steadily rising due to an aging
      population and more frequent imaging of the abdomen for other medical conditions.
      While surgery remains the standard of care treatment for localized disease, many
      patients are unfit due to their advanced age and medical comorbidities. In these
      patients, an active surveillance strategy or ablative therapies, including
      radiofrequency/microwave ablation or cryotherapy, can be offered. Such options
      have limitations particularly with fast growing, or larger tumors. A promising
      ablative therapy option to consider is stereo-tactic body radiotherapy (SBRT).
      SBRT refers to high dose, focally ablative radiation delivered in a short time (3
      5 fractions), and is safe and effective in many other cancer sites, including
      lung, liver and spine. SBRT offers potential advantages in the primary kidney
      cancer setting due to its ablative dosing (overcoming the notion of "radio
      resistance"), short treatment duration (important in an elderly population), low
      toxicity profile (enabling SBRT to treat larger RCCs than other ablative
      modalities), and non-invasiveness. To date, there is limited long-term
      prospective data on the outcomes of SBRT in primary RCC. However, early evidence
      is intriguing with respect to excellent local control and low toxicity; however,
      most studies vary in terms of technique and radiation dosing used. Well-designed
      prospective cohort studies with clearly defined and standardized techniques,
      dosing, follow-up, and integration of quality of life outcomes will be essential
      to further establish the role of SBRT in management of inoperable, localized RCC.

PMID- 26316915
TI  - The CUA-AUA International Fellows Exchange Program: New Orleans 2015.

PMID- 26316916
TI  - Metastatic Renal Cell Cancer: Summary from ASCO 2015.

PMID- 26316917
TI  - Prostate Cancer: Summary from ASCO 2015.

PMID- 26316918
TI  - Optical Coherence Tomography Monitoring Strategies for A-VEGF-Treated Age-Related
      Macular Degeneration: An Evidence-Based Analysis.
AB  - BACKGROUND: New anti-angiogenesis pharmacotherapies have dramatically altered
      treatment of age-related macular degeneration (AMD), the leading cause of
      blindness in older adults. Monthly intraocular injections however, are extremely
      burdensome to ophthalmologists, patients, and their families. Repeated injections
      also increase risks of complications or adverse events. Although the
      pharmacokinetics of anti-vascular endothelial growth factor (A-VEGF) drugs are
      fairly well known, an individuals' AMD presentation and their pharmacodynamics or
      response to the drug has been shown to be extremely variable. Therefore treating
      everyone on the same fixed or standard regimen has potential for undertreating or
      overtreating patients, and drug costs are not trivial. OBJECTIVES: To review
      monitoring strategies and to evaluate the role of optical coherence tomography
      (OCT) in guiding management of A-VEGF-treated neovascular AMD (n-AMD) patients.
      DATA SOURCES: Systematic reviews of biographic databases for studies published
      between 2008 and February 2013 involving A-VEGF-treated n-AMD patients monitored
      in longitudinal follow-up. REVIEW METHODS: Studies were grouped according to
      varying treatments, monitoring schedules, and re-treatment protocols reported for
      n-AMD patients treated with A-VEGF. Several outcomes were evaluated across
      strategies including visual acuity (VA), retinal anatomy, re-treatment criteria
      and frequencies of clinical follow-up, OCT imaging investigations, and
      intravitreal injections. Results were summarized qualitatively, as heterogeneity
      in study objectives and methods precluded formal meta-analysis. RESULTS: A
      systematic review identified 18 randomized controlled trials (RCTs) and 20
      observational studies involving A-VEGF treatment employing various monitoring and
      as-needed (PRN) re-treatment protocols. Several maintenance strategies were
      unsuccessful, resulting in lower VA gains and stabilization than monthly
      injections in A-VEGF-treated n-AMD. These included fixed quarterly treatment;
      fixed quarterly monitoring and PRN re-treatment; and monthly monitoring with
      either VA-guided re-treatment or quantitative-only VA/OCT- (central retinal
      thickness [CRT] > 100 MUm) guided re-treatment. PRN re-treatment strategies with
      A-VEGF on the basis of monthly follow-up and rigorous reviews of OCT qualitative
      and quantitative measures of disease activity did decrease injection burden while
      maintaining visual gains. Gains in VA obtained with PRN re-treatment in usual
      clinical practice, however, were not as high as gains in clinical trials.
      CONCLUSIONS: To reduce treatment burden and provide a more individualized
      treatment strategy for n-AMD patients, OCT/VA-guided PRN treatment strategies
      have become the preferred and the dominant maintenance strategy. Success of these
      strategies, however, is dependent on close monitoring and adherence to tightly
      defined re-treatment criteria.

PMID- 26316919
TI  - Multiple Intravenous Infusions Phase 2b: Laboratory Study.
AB  - BACKGROUND: Administering multiple intravenous (IV) infusions to a single patient
      via infusion pump occurs routinely in health care, but there has been little
      empirical research examining the risks associated with this practice or ways to
      mitigate those risks. OBJECTIVES: To identify the risks associated with multiple
      IV infusions and assess the impact of interventions on nurses' ability to safely
      administer them. DATA SOURCES AND REVIEW METHODS: Forty nurses completed infusion
      related tasks in a simulated adult intensive care unit, with and without
      interventions (i.e., repeated-measures design). RESULTS: Errors were observed in
      completing common tasks associated with the administration of multiple IV
      infusions, including the following (all values from baseline, which was current
      practice): setting up and programming multiple primary continuous IV infusions
      (e.g., 11.7% programming errors)identifying IV infusions (e.g., 7.7% line-tracing
      errors)managing dead volume (e.g., 96.0% flush rate errors following IV syringe
      dose administration)setting up a secondary intermittent IV infusion (e.g., 11.3%
      secondary clamp errors)administering an IV pump bolus (e.g., 11.5% programming
      errors)Of 10 interventions tested, 6 (1 practice, 3 technology, and 2
      educational) significantly decreased or even eliminated errors compared to
      baseline. LIMITATIONS: The simulation of an adult intensive care unit at 1
      hospital limited the ability to generalize results. The study results were
      representative of nurses who received training in the interventions but had
      little experience using them. The longitudinal effects of the interventions were
      not studied. CONCLUSIONS: Administering and managing multiple IV infusions is a
      complex and risk-prone activity. However, when a patient requires multiple IV
      infusions, targeted interventions can reduce identified risks. A combination of
      standardized practice, technology improvements, and targeted education is
      required.

PMID- 26316920
TI  - Frequency of Testing for Dyslipidemia: An Evidence-Based Analysis.
AB  - BACKGROUND: Dyslipidemias include high levels of total cholesterol, low-density
      lipoprotein (LDL) cholesterol, and triglycerides and low levels of high-density
      lipoprotein (HDL) cholesterol. Dyslipidemia is a risk factor for cardiovascular
      disease, which is a major contributor to mortality in Canada. Approximately 23%
      of the 2009/11 Canadian Health Measures Survey (CHMS) participants had a high
      level of LDL cholesterol, with prevalence increasing with age, and approximately
      15% had a total cholesterol to HDL ratio above the threshold. OBJECTIVES: To
      evaluate the frequency of lipid testing in adults not diagnosed with dyslipidemia
      and in adults on treatment for dyslipidemia. RESEARCH METHODS: A systematic
      review of the literature set out to identify randomized controlled trials (RCTs),
      systematic reviews, health technology assessments (HTAs), and observational
      studies published between January 1, 2000, and November 29, 2012, that evaluated
      the frequency of testing for dyslipidemia in the 2 populations. RESULTS: Two
      observational studies assessed the frequency of lipid testing, 1 in individuals
      not on lipid-lowering medications and 1 in treated individuals. Both studies were
      based on previously collected data intended for a different objective and,
      therefore, no conclusions could be reached about the frequency of testing at
      intervals other than the ones used in the original studies. Given this limitation
      and generalizability issues, the quality of evidence was considered very low. No
      evidence for the frequency of lipid testing was identified in the 2 HTAs
      included. Canadian and international guidelines recommend testing for
      dyslipidemia in individuals at an increased risk for cardiovascular disease. The
      frequency of testing recommended is based on expert consensus. CONCLUSIONS:
      Conclusions on the frequency of lipid testing could not be made based on the 2
      observational studies. Current guidelines recommend lipid testing in adults with
      increased cardiovascular risk, with the frequency of testing based on individual
      cardiovascular risk.

PMID- 26316921
TI  - Frequency of Testing for Dyslipidemia: A Systematic Review and Budget Impact
      Analysis.
AB  - BACKGROUND: Current Canadian guidelines recommend annual screening for
      hyperlipidemia in people with a Framingham risk score (FRS) of greater than 5%.
      In those with a FRS of less than 5%, lipid screening is recommended every 3 to 5
      years. OBJECTIVES: We aimed to determine the most cost-effective frequency of
      lipid profile testing in adults with different levels of cardiovascular risk
      based on published literature, to determine current frequency of lipid screening
      in Ontario, and to calculate the cost of aligning current with recommended
      frequencies. METHODS: We systematically searched for studies (from 2000 to 2012)
      evaluating the cost-effectiveness of lipid profile testing frequency in adults.
      Using the Canadian Community Health Survey and linked health administrative
      databases, we calculated the FRS for each survey respondent on every day from
      2005 to 2011. Average current frequency of lipid testing was calculated according
      to the total number of patient days spent in each FRS category and the number of
      lipid tests occurring on those days. Extrapolating these outcomes to the Ontario
      population, we estimated the expected budget impact of aligning current rates of
      lipid testing with rates recommended by the Canadian Cardiovascular Society (CCS)
      guidelines. RESULTS: No studies evaluated the cost-effectiveness of lipid
      monitoring frequency. Our database analysis revealed that people in the very low
      risk group are tested an average of once every 4.4 years, those in the low risk
      group are tested once every 2 years, those in the intermediate risk group are
      tested every 1.4 years, and those in the highest risk group are tested annually.
      If we compare these rates to those recommended by the CCS guidelines, an
      additional 3.6 million tests would be needed to achieve recommended rates of
      lipid testing. At a cost of $14.48 per test, the expected cost to the province
      would be $52.2 million. LIMITATIONS: The results were analysed in aggregate,
      leading to the potential for ecological fallacy. In addition, because data
      pertaining to drug prescriptions in Ontario are only available for people over 65
      years of age, the analysis did not account for the influence of statin treatment
      on the frequency of lipid testing. CONCLUSIONS: Our findings show that there is
      currently no evidence to inform the optimal frequency of lipid testing. People in
      Ontario at low-low, low, intermediate, and high risk are being tested once every
      4.4, 1.9, 1.4, and 1.0 times per year, respectively. According to the CCS
      guidelines, this represents under-testing in the low and intermediate groups.
      Achieving the recommended rates of testing would cost approximately $52.2
      million. Given the large cost of implementing such a change and the uncertainty
      on which CCS guidelines are based, it would be prudent to await the results of
      further research before making such a large investment.

PMID- 26316922
TI  - Point-of-Care Hemoglobin A1c Testing: An Evidence-Based Analysis.
AB  - BACKGROUND: The increasing prevalence of diabetes in Ontario means that there
      will be growing demand for hemoglobin A1c (HbA1c) testing to monitor glycemic
      control for the management of this chronic disease. Testing HbA1c where patients
      receive their diabetes care may improve system efficiency if the results from
      point-of-care HbA1c testing are comparable to those from laboratory HbA1c
      measurements. OBJECTIVES: To review the correlation between point-of-care HbA1c
      testing and laboratory HbA1c measurement in patients with diabetes in clinical
      settings. DATA SOURCES: The literature search included studies published between
      January 2003 and June 2013. Search terms included glycohemoglobin, hemoglobin
      A1c, point of care, and diabetes. REVIEW METHODS: Studies were included if
      participants had diabetes; if they compared point-of-care HbA1c devices (licensed
      by Health Canada and available in Canada) with laboratory HbA1c measurement
      (reference method); if they performed point-of-care HbA1c testing using capillary
      blood samples (finger pricks) and laboratory HbA1c measurement using venous blood
      samples within 7 days; and if they reported a correlation coefficient between
      point-of-care HbA1c and laboratory HbA1c results. RESULTS: Three point-of-care
      HbA1c devices were reviewed in this analysis: Bayer's A1cNow+, Bio-Rad's In2it,
      and Siemens' DCA Vantage. Five observational studies met the inclusion criteria.
      The pooled results showed a positive correlation between point-of-care HbA1c
      testing and laboratory HbA1c measurement (correlation coefficient, 0.967; 95%
      confidence interval, 0.960-0.973). LIMITATIONS: Outcomes were limited to the
      correlation coefficient, as this was a commonly reported measure of analytical
      performance in the literature. Results should be interpreted with caution due to
      risk of bias related to selection of participants, reference standards, and the
      multiple steps involved in POC HbA1c testing. CONCLUSIONS: Moderate quality
      evidence showed a positive correlation between point-of-care HbA1c testing and
      laboratory HbA1c measurement. Five observational studies compared 3 point-of-care
      HbA1c devices with laboratory HbA1c assays, and all reported strong correlation
      between the 2 tests.

PMID- 26316923
TI  - Point-of-Care Hemoglobin A1c Testing: A Budget Impact Analysis.
AB  - BACKGROUND: The increasing prevalence of diabetes in Ontario means that there
      will be growing demand for hemoglobin A1c (HbA1c) testing to monitor glycemic
      control as part of managing this chronic disease. Testing HbA1c where patients
      receive their diabetes care may improve system efficiency if the results from
      point-of-care HbA1c testing are comparable to those from laboratory HbA1c
      measurements. OBJECTIVES: To estimate the budget impact of point-of-care HbA1c
      testing to replace laboratory HbA1c measurement for monitoring glycemic control
      in patients with diabetes in 2013/2014. REVIEW METHODS: This analysis compared
      the average testing cost of 3 point-of-care HbA1c devices licensed by Health
      Canada and available on the market in Canada (Bayer's A1cNow+, Siemens's DCA
      Vantage, and Bio Rad's In2it), with that of the laboratory HbA1c reference
      method. The cost difference between point-of-care HbA1c testing and laboratory
      HbA1c measurement was calculated. Costs and the corresponding range of net impact
      were estimated in sensitivity analyses. RESULTS: The total annual costs of
      laboratory HbA1c measurement and point-of-care HbA1c testing for 2013/2014 were
      $91.5 million and $86.8 million, respectively. Replacing all laboratory HbA1c
      measurements with point-of-care HbA1c testing would save approximately $4.7
      million over the next year. Savings could be realized by the health care system
      at each level that point-of-care HbA1c testing is substituted for laboratory
      HbA1c measurement. If physician fees were excluded from the analysis, the health
      care system would incur a net impact from using point-of-care HbA1c testing
      instead of laboratory A1c measurement. LIMITATIONS: Point-of-care HbA1c
      technology is already in use in the Ontario health care system, but the current
      uptake is unclear. Knowing the adoption rate and market share of point-of-care
      HbA1c technology would allow for a more accurate estimate of budget impact.
      CONCLUSIONS: Replacing laboratory HbA1c measurement with point-of-care HbA1c
      testing or using point-of-care HbA1c testing in combination with laboratory HbA1c
      measurement to monitor glycemic control in patients with diabetes could have
      saved the province $1,175,620 to $4,702,481 in 2013/2014.

PMID- 26316924
TI  - Preventing Heart Failure in Inflammatory and Immune Disorders.
AB  - Patients with chronic inflammatory diseases are at increased risk for heart
      failure due to ischemic heart disease and other causes including heart failure
      with preserved ejection fraction. Using rheumatoid arthritis and treated HIV
      infection as two prototypical examples, we review the epidemiology and potential
      therapies to prevent heart failure in these populations. Particular focus is
      given to anti-inflammatory therapies including statins and biologic disease
      modifying drugs. There is also limited evidence for lifestyle changes and
      blockade of the renin-angiotensin-aldosterone system. We conclude by proposing
      how a strategy for heart failure prevention, such as the model tested in the
      Screening To Prevent Heart Failure (STOP-HF) trial, may be adapted to chronic
      inflammatory disease.

PMID- 26316925
TI  - Illness Perceptions in Women with Breast Cancer-a Systematic Literature Review.
AB  - Women with breast cancer respond to the illness and its medical management in
      their own personal way. Their coping behavior and self-management are determined
      by their views (cognitions) and feelings (emotions) about symptoms and illness:
      their illness perceptions. This paper reports the results of a systematic
      literature review of illness perceptions and breast cancer. In the 12 studies
      identified, published between 2012 and 2015, illness perceptions were found to be
      important concomitants of medical and behavioral outcomes: fear of recurrence,
      distress, quality of life, satisfaction with medical care, use of traditional
      healers, and risk perception. Intervention studies are called for where the
      effects are examined of replacing unhelpful illness perceptions by more
      constructive ones. Health care providers do well by incorporating illness
      perceptions in their care for women with breast cancer, as this is instrumental
      in improving patients' quality of life.

PMID- 26309729
TI  - Case Report: Perioperative management of a pregnant poly trauma patient for spine
      fixation surgery.
AB  - Trauma is estimated to complicate approximately one in twelve pregnancies, and is
      currently a leading non-obstetric cause of maternal death. Pregnant trauma
      patients requiring non-obstetric surgery pose a number of challenges for
      anesthesiologists. Here we present the successful perioperative management of a
      pregnant trauma patient with multiple injuries including occult pneumothorax who
      underwent T9 to L1 fusion in prone position, and address the pertinent
      perioperative anesthetic considerations and management. 

PMID- 26309730
TI  - Re-analysis of metagenomic sequences from acute flaccid myelitis patients reveals
      alternatives to enterovirus D68 infection.
AB  - Metagenomic sequence data can be used to detect the presence of infectious
      viruses and bacteria, but normal microbial flora make this process challenging.
      We re-analyzed metagenomic RNA sequence data collected during a recent outbreak
      of acute flaccid myelitis (AFM), caused in some cases by infection with
      enterovirus D68. We found that among the patients whose symptoms were previously
      attributed to enterovirus D68, one patient had clear evidence of infection with
      Haemophilus influenzae, and a second patient had a severe Staphylococcus aureus
      infection caused by a methicillin-resistant strain. Neither of these bacteria
      were identified in the original study. These observations may have relevance in
      cases that present with flaccid paralysis because bacterial infections, co
      infections or post-infection immune responses may trigger pathogenic processes
      that may present as poliomyelitis-like syndromes and may mimic AFM.  A separate
      finding was that large numbers of human sequences were present in each of the
      publicly released samples, although the original study reported that human
      sequences had been removed before deposition. 

PMID- 26316928
TI  - The Sleeve Bypass Trial: a multicentre randomized controlled trial comparing the
      long term outcome of laparoscopic sleeve gastrectomy and gastric bypass for
      morbid obesity in terms of excess BMI loss percentage and quality of life.
AB  - BACKGROUND: Obesity is an increasing disease worldwide. Bariatric surgery is the
      only effective therapy to induce sufficient long-term weight loss for morbidly
      obese patients. Laparoscopic Roux-en-Y Gastric Bypass (LRYGB) is the gold
      standard surgical technique. Laparoscopic Sleeve Gastrectomy (LSG) is a new
      promising bariatric procedure which has the advantage of maintaining an intact
      gastrointestinal tract. The aim of this study is to evaluate the efficiency of
      both techniques. Our hypothesis is that LSG has a similar percentage excess BMI
      loss (%EBMIL) after 5 years compared to LRYGB. METHODS/DESIGN: The Sleeve Bypass
      Trial is a randomized multicentre clinical trial: patients eligible for bariatric
      surgery are randomized to either LSG or LRYGB. Patients with a body mass index
      (BMI) >= 40 kg/m(2) or BMI 35 kg/m(2) with obesity related comorbidity (T2 DM,
      sleep apnoea, hypertension) are eligible for randomization. At randomization
      patients are stratified for centre, sex, T2 DM and BMI >= 50 kg/m(2). A total
      number of 620 patients will be enrolled and equally (1:1) randomized to both
      treatment arms. Only surgeons experienced in both operation techniques will
      participate in the Sleeve Bypass trial. The primary endpoint is the 5-year weight
      loss (%EBMIL) of LSG and LRYGB. Secondary endpoints are resolution of obesity
      related comorbidity, complications, revision bariatric surgery and quality of
      life (QOL) defined in various questionnaires. DISCUSSION: Long-term %EBMIL
      between the two treatment strategies used to be in favour of LRYGB, but more
      recent results throughout the world show similar %EBMIL in both techniques. If
      weight loss is comparable, obesity-related comorbidity and QOL after bariatric
      procedures should be taken into account when deciding on which surgical technique
      is to be preferred for certain subgroups in the future. TRIAL REGISTRATION: Dutch
      Trial Register: NTR 4741.

PMID- 26316929
TI  - Becker and the Demographic Transition.

PMID- 26316930
TI  - Prognostic Factors in Advanced Non-Small-Cell Lung Cancer Patients: Patient
      Characteristics and Type of Chemotherapy.
AB  - Eleven prognostic factors were retrospectively analyzed in 270 newly diagnosed
      patients with advanced non-small-cell lung cancer including age, sex, performance
      status, histology, stage, smoking status, hemoglobin level, forced expiratory
      volume in one second (FEV1), weight loss >5% in 3 months preceding therapy,
      number of involved organs, and type of first-line chemotherapy. Response rate was
      35.6%, and median survival was 8.2 months (95% CI, 7.8 to 8.7) for the whole
      group. Age <=60 years (P = .016), FEV1 >= 2L (P = .03), and the use of
      platinum/docetaxel (P < .0001) were significantly associated with an improved
      survival. Histology did not affect outcome in the absence of targeted therapies. 

PMID- 26316931
TI  - Aggressive Palliation in Extensive Stage Small Cell Lung Cancer, Practice
      Guidelines versus Clinical Practice: A Case Report and Review of the Literature.
AB  - Small cell lung cancer (SCLC) constitutes approximately 16% of all primary lung
      cancers, with more than 35,000 new cases per year. Two-thirds of patients present
      with extensive stage disease (ES-SCLC) due to a tendency to metastasize early.
      Outcomes remain poor, with a median survival of approximately 10 months and a two
      year overall survival of <10%. Current recommendations call for combination
      chemotherapy alone in patients without localized symptoms. Thoracic radiation
      therapy following a good clinical response is controversial. We report on a
      patient with ES-SCLC that had an excellent response to chemotherapy and underwent
      whole brain radiotherapy for a known brain metastasis and consolidative
      radiotherapy to the thorax. His latest follow-up demonstrates only a stable
      residual pulmonary nodule and no evidence of active metastatic disease. ES-SCLC
      is a relatively common presentation with a variable burden of metastatic disease.
      In the absence of randomized trials demonstrating the efficacy of thoracic
      radiation therapy, the community radiation oncologist is placed in a difficult
      position when addressing these patients, particularly those with otherwise good
      performance status and a good response to initial systemic chemotherapy. More
      research in this area is sorely needed to help guide treatment recommendations. 

PMID- 26316932
TI  - An Atypical Presentation with Diagnostic Challenge of a Large Cell Neuroendocrine
      Cancer of Lung: A Case Report and Review of the Literature.
AB  - Large-cell neuroendocrine carcinomas (LCNECs) are relatively rare and aggressive
      neoplasms of the lung with very poor prognosis. Even though they are included in
      the classification of nonsmall cell carcinomas, they have a biological behaviour
      and physiological response to treatment more like small cell carcinomas of lung.
      We report an atypical case presentation of LCNEC in a 51-year-old gentleman who
      presented with diffuse metastases to the thoracic and lumbar spine, brain, and
      liver, posing a diagnostic challenge. The primary small central lung tumor was in
      close proximity to major vessels, rendering a biopsy of the primary cancer
      challenging and nearly impossible. The final diagnosis was established through
      immunohistochemistry staining and examination of liver biopsy from a metastatic
      lesion. We also included a review of the current literature pertinent to LCNEC,
      as well as the important role of tumor markers plus immunohistochemistry profiles
      in determining the origin of unknown primary tumors in such difficult patient
      presentations. 

PMID- 26316933
TI  - Treatment of Non-Small-Cell Lung Cancer with Erlotinib following Gefitinib
      Induced Hepatotoxicity: Review of 8 Clinical Cases.
AB  - Objective. Gefitinib often induces liver damage. A few reports have described
      that the subsequent administration of erlotinib was associated with less
      hepatotoxicity, but the safety and efficacy of this treatment are still not fully
      investigated. Therefore, we evaluated retrospectively the patients with erlotinib
      following gefitinib-induced hepatotoxicity. Methods and Patients. We
      retrospectively reviewed the medical records between December 2007 and March
      2010. The patients were evaluated including the following information: age,
      gender, histology of lung cancer, performance status, smoking status, epidermal
      growth factor receptor (EGFR) mutation status, liver metastasis, viral hepatitis,
      alcoholic liver injury, clinical response, and hepatotoxicity due to EGFR
      tyrosine kinase inhibitors. Results. We identified 8 patients with erlotinib
      following gefitinib-induced hepatotoxicity. All achieved disease control by
      gefitinib. Hepatotoxicity was grades 2 and 3 in 3 and 5 patients, respectively.
      The median duration of treatment with gefitinib was 112.5 days and the median
      time to gefitinib-induced hepatotoxicity was 51.5 days. The median duration of
      treatment with erlotinib was 171.5 days. Grade 1 and 2 erlotinib-induced
      hepatotoxicity was observed in 2 and 1 patient, respectively. Conclusions.
      Erlotinib administration with careful monitoring is thought to be a good
      alternative strategy for patients who respond well to gefitinib treatment but
      experience hepatotoxicity. 

PMID- 26316934
TI  - Preoperative Total Serum Cholesterol and Patients' Survival in Resected Nonsmall
      Cell Lung Cancer.
AB  - The association between hypocholesterolemia and lung cancer risk has been
      confirmed in some studies. The purpose of the study was to determine whether
      preoperative hypocholesterolemia (below normal range) is a prognostic factor for
      survival after nonsmall cell lung cancer (NSCLC) resection. Two hundred and sixty
      two consecutive cases of resected NSCLC with a followup period for more than 5
      years were reviewed retrospectively. In our results, there were only 13/262
      patients having hypocholesterolemia. A significant association was observed
      between preoperative hypocholesterolemia and patients' survival. However, we
      failed to find the prognostic significance of preoperative hypocholesterolemia by
      univariate analysis. No statistical differences were also found by the comparison
      between 5-year survivors and the others. Our data indicates a trend toward an
      association between preoperative hypocholesterolemia and poorer survival in
      NSCLC; however, it did not reach statistical significance. 

PMID- 26316935
TI  - Mutated KRAS Is an Independent Negative Prognostic Factor for Survival in NSCLC
      Stage III Disease Treated with High-Dose Radiotherapy.
AB  - Background. The main attention regarding prognostic and predictive markers in
      NSCLC directs towards the EGFR-targeted pathway, where the most studied genetic
      alterations include EGFR mutations, EGFR copy number, and KRAS mutations. We
      wanted to explore the prognostic impact of mutated KRAS in the stage III setting
      treated with high-dose radiochemotherapy. Methods. Samples were obtained from
      patients participating in two prospective studies of locally advanced NSCLC
      receiving combined radiochemotherapy: the RAKET study, a randomized phase II
      study where patients were treated with induction chemotherapy
      (carboplatin/paclitaxel) followed by concurrent radiochemotherapy, and the
      Satellite trial, a phase II study with induction chemotherapy
      (cisplatin/docetaxel) followed by radiotherapy concurrent cetuximab. The samples
      were analysed regarding KRAS mutations, EGFR mutations, and EGFR FISH positivity.
      Results. Patients with mutated KRAS had a significantly inferior survival, which
      maintained its significance in a multivariate analysis when other possible
      prognostic factors were taken into account. The prevalence of KRAS mutations,
      EGFR mutations, and EGFR FISH positivity were 28.8%, 7.5%, and 19.7%,
      respectively. Conclusion. Mutated KRAS is an independent negative prognostic
      factor for survival in NSCLC stage III disease treated with combined
      radiochemotherapy. The prevalence of KRAS mutations and EGFR mutations are as
      expected in this Scandinavian population. 

PMID- 26316936
TI  - Against Lung Cancer Cells: To Be, or Not to Be, That Is the Problem.
AB  - Tobacco smoke and radioactive radon gas impose a high risk for lung cancer. The
      radon-derived ionizing radiation and some components of cigarette smoke induce
      oxidative stress by generating reactive oxygen species (ROS). Respiratory lung
      cells are subject to the ROS that causes DNA breaks, which subsequently bring
      about DNA mutagenesis and are intimately linked with carcinogenesis. The damaged
      cells by oxidative stress are often destroyed through the active apoptotic
      pathway. However, the ROS also perform critical signaling functions in stress
      responses, cell survival, and cell proliferation. Some molecules enhance
      radiation-induced tumor cell killing via the reduction in DNA repair levels.
      Hence the DNA repair levels may be a novel therapeutic modality in overcoming
      drug resistance in lung cancer. Either survival or apoptosis, which is determined
      by the balance between DNA damage and DNA repair levels, may lender the major
      problems in cancer therapy. The purpose of this paper is to take a closer look at
      risk factor and at therapy modulation factor in lung cancer relevant to the ROS. 

PMID- 26316937
TI  - Molecular Markers with Predictive and Prognostic Relevance in Lung Cancer.
AB  - Lung cancer accounts for the majority of cancer-related deaths worldwide of which
      non-small-cell lung carcinoma alone takes a toll of around 85%. Platinum-based
      therapy is the stronghold for lung cancer at present. The discovery of various
      molecular alterations that underlie lung cancer has contributed to the
      development of specifically targeted therapies employing specific mutation
      inhibitors. Targeted chemotherapy based on molecular profiling has shown great
      promise in lung cancer treatment. Various molecular markers with predictive and
      prognostic significance in lung cancer have evolved as a result of advanced
      research. Testing of EGFR and Kras mutations is now a common practice among
      community oncologists, and more recently, ALK rearrangements have been added to
      this group. This paper discusses various predictive and prognostic markers that
      are being investigated and have shown significant relevance which can be
      exploited for targeted treatment in lung cancer. 

PMID- 26316938
TI  - Cigarette Smoking and Lung Cancer: Pediatric Roots.
AB  - A vast array of data suggests that early age of smoking onset enhances the risk
      for development of lung cancer in adulthood. Initiation of smoking at a young age
      may influence the development of lung cancer because of its effect on duration of
      smoking. Early onset of smoking also may serve as an independent risk factor. It
      may increase the likelihood that smoking occurs during a critical period of
      development that enhances susceptibility to the adverse effects of cancer causing
      agents in cigarette smoke, thereby facilitating the initiation of the
      carcinogenic process. While evidence for the latter hypothesis derives from a
      variety of sources, definitive proof has proven elusive. Whether or not early age
      of smoking serves as an independent risk factor for lung carcinogenesis, the
      consensus of the public health community is that prevention of smoking onset at a
      young age and early cessation are keys to stemming the current lung cancer
      pandemic. Population approaches to tobacco prevention and control, such as
      measures contained in the World Health Organization Framework Convention Tobacco
      Control Treaty, offer the best opportunity, on the scale needed, to create a
      smoke-free world and bring an end to the pandemic of tobacco-related disease. 

PMID- 26316939
TI  - Helicobacter pylori Infection and Risk of Lung Cancer: A Meta-Analysis.
AB  - Background. Recent evidence showed that Helicobacter pylori seropositivity is a
      risk factor for gastric and several other cancers. However, evidence on H. pylori
      infection and risk of lung cancer has been controversial, with a limited number
      of underpowered studies. We therefore examined the association between H. pylori
      infection and risk of lung cancer. Methods. A comprehensive literature search was
      performed using PubMed, EMBASE (until October 2012) for studies investigating an
      association between Helicobacter pylori (H. pylori) infection and risk of lung
      cancer. Pooled odds ratio (OR) was calculated using random-effects model.
      Subgroup and sensitivity analysis were also done. Results. A total of seven
      studies (6 case-control and 1 cohort study) were included for the analysis. There
      was a significant heterogeneity among the studies, but no publication bias was
      observed. We found that H. pylori infection was associated with significantly
      increased risk of lung cancer (pooled OR, 2.29 (95% CI, 1.34-3.91) P = 0.01).
      Conclusions. Our meta-analysis suggests a significant increased risk of lung
      cancer in patients with H. pylori infection. Further research is needed to
      confirm these findings and to identify the underlying biological mechanisms. 

PMID- 26316941
TI  - Potential Pitfall in the Assessment of Lung Cancer with FDG-PET/CT: Talc
      Pleurodesis Causes Intrathoracic Nodal FDG Avidity.
AB  - Objective. Talc pleurodesis is a common procedure performed to treat
      complications related to lung cancer. The purpose of our study was to
      characterize any thoracic nodal findings on FDG PET/CT associated with prior talc
      pleurodesis. Materials and Methods. The electronic medical record identified 44
      patients who underwent PET/CT between January 2006 and December 2010 and had a
      history of talc pleurodesis. For each exam, we evaluated the distribution
      pattern, size, and attenuation of intrathoracic lymph nodes and the associated
      standardized uptake value. Results. High-attenuation intrathoracic lymph nodes
      were noted in 11 patients (25%), and all had corresponding increased FDG uptake
      (range 2-9 mm). Involved nodal groups were anterior peridiaphragmatic (100%),
      paracardiac (45%), internal mammary (25%), and peri-IVC (18%) nodal stations.
      Seven of the 11 patients (63%) had involvement of multiple lymph nodal groups.
      Mean longitudinal PET/CT and standalone CT followups of 15 +/- 11 months showed
      persistence of both high-attenuation and increased uptake at these sites, without
      increase in nodal size suggesting metastatic disease involvement. Conclusions.
      FDG avid, high-attenuation lymph nodes along the lymphatic drainage pathway for
      parietal pleura are a relatively common finding following talc pleurodesis and
      should not be mistaken for nodal metastases during the evaluation of patients
      with history of lung cancer. 

PMID- 26316940
TI  - Thymidylate Synthase as a Predictive Biomarker for Pemetrexed Response in NSCLC.
AB  - In recent years, major strides in cancer research have made it possible to select
      personalized chemotherapy recommendations based on an individual patient's tumor
      biology. The prognostic and/or predictive ability of biomarkers seeks to tailor
      the use of targeted chemotherapy and can result in improved clinical outcomes
      with reduced toxicity. A proliferation of new technology and pharmacotherapeutics
      in the setting of current FDA Clinical Laboratory Improvement Amendment (CLIA)
      standards has resulted in a recent surge in direct-to-physician biomarker tests.
      However, in the absence of clinical validation, there is the concern that the
      biomarkers may be utilized prematurely, resulting in improper chemotherapy
      selection and patient harm. Thymidylate synthase (TS) has been marketed as a
      predictive biomarker for the use of pemetrexed in NSCLC. We will examine the
      evidence behind the use of TS as a predictive biomarker to predict response to
      pemetrexed in NSCLC. At this time, the evidence does not currently support using
      TS assays to guide chemotherapy selection outside of a clinical research
      protocol. 

PMID- 26316942
TI  - National Mesothelioma Virtual Bank: A Platform for Collaborative Research and
      Mesothelioma Biobanking Resource to Support Translational Research.
AB  - The National Mesothelioma Virtual Bank (NMVB), developed six years ago, gathers
      clinically annotated human mesothelioma specimens for basic and clinical science
      research. During this period, this resource has greatly increased its collection
      of specimens by expanding the number of contributing academic health centers
      including New York University, University of Pennsylvania, University of
      Pittsburgh Medical Center, and Mount Sinai School of Medicine. Marketing efforts
      at both national and international annual conferences increase awareness and
      availability of the mesothelioma specimens at no cost to approved investigators,
      who query the web-based NMVB database for cumulative and appropriate patient
      clinicopathological information on the specimens. The data disclosure and
      specimen distribution protocols are tightly regulated to maintain compliance with
      participating institutions' IRB and regulatory committee reviews. The NMVB
      currently has over 1120 annotated cases available for researchers, including
      paraffin embedded tissues, fresh frozen tissue, tissue microarrays (TMA), blood
      samples, and genomic DNA. In addition, the resource offers expertise and
      assistance for collaborative research. Furthermore, in the last six years, the
      resource has provided hundreds of specimens to the research community. The
      investigators can request specimens and/or data by submitting a Letter of Intent
      (LOI) that is evaluated by NMVB research evaluation panel (REP). 

PMID- 26316943
TI  - Attitudes towards Lung Cancer Screening in an Australian High-Risk Population.
AB  - Objectives. To determine whether persons at high risk of lung cancer would
      participate in lung cancer screening test if available in Australia and to elicit
      general attitudes towards cancer screening and factors that might affect
      participation in a screening program. Methods. We developed a 20-item written
      questionnaire, based on two published telephone interview scripts, addressing
      attitudes towards cancer screening, perceived risk of lung cancer, and
      willingness to be screened for lung cancer and to undertake surgery if lung
      cancer were detected. The questionnaire was given to 102 current and former
      smokers attending the respiratory clinic and pulmonary rehabilitation programmes.
      Results. We gained 90 eligible responses (M:F, 69:21). Mean [SD] age was 63 [11]
      and smoking history was 32 [21] pack years. 95% of subjects would participate in
      a lung cancer screening test, and 91% of these would consider surgery if lung
      cancer was detected. 44% of subjects considered that they were at risk of lung
      cancer. This was lower in ex-smokers than in current smokers. Conclusions. There
      is high willingness for lung cancer screening and surgical treatment. There is
      underrecognition of risk among ex-smokers. This misperception could be a barrier
      to a successful screening or case-finding programme in Australia. 

PMID- 26316945
TI  - Simple and Objective Prediction of Survival in Patients with Lung Cancer: Staging
      the Host Systemic Inflammatory Response.
AB  - Background. Prediction of survival in patients diagnosed with lung cancer remains
      problematical. The aim of the present study was to examine the clinical utility
      of an established objective marker of the systemic inflammatory response, the
      Glasgow Prognostic Score, as the basis of risk stratification in patients with
      lung cancer. Methods. Between 2005 and 2008 all newly diagnosed lung cancer
      patients coming through the multidisciplinary meetings (MDTs) of four Scottish
      centres were included in the study. The details of 882 patients with a confirmed
      new diagnosis of any subtype or stage of lung cancer were collected
      prospectively. Results. The median survival was 5.6 months (IQR 4.8-6.5).
      Survival analysis was undertaken in three separate groups based on mGPS score. In
      the mGPS 0 group the most highly predictive factors were performance status,
      weight loss, stage of NSCLC, and palliative treatment offered. In the mGPS 1
      group performance status, stage of NSCLC, and radical treatment offered were
      significant. In the mGPS 2 group only performance status and weight loss were
      statistically significant. Discussion. This present study confirms previous work
      supporting the use of mGPS in predicting cancer survival; however, it goes
      further by showing how it might be used to provide more objective risk
      stratification in patients diagnosed with lung cancer. 

PMID- 26316944
TI  - Alveolar Macrophage Polarisation in Lung Cancer.
AB  - The role of alveolar macrophages in lung cancer is multifaceted and conflicting.
      Alveolar macrophage secretion of proinflammatory cytokines has been found to
      enhance antitumour functions, cytostasis (inhibition of tumour growth), and
      cytotoxicity (macrophage-mediated killing). In contrast, protumour functions of
      alveolar macrophages in lung cancer have also been indicated. Inhibition of
      antitumour function via secretion of the anti-inflammatory cytokine IL-10 as well
      as reduced secretion of proinflammatory cytokines and reduction of mannose
      receptor expression on alveolar macrophages may contribute to lung cancer
      progression and metastasis. Alveolar macrophages have also been found to
      contribute to angiogenesis and tumour growth via the secretion of IL-8 and VEGF.
      This paper reviews the evidence for a dual role of alveolar macrophages in lung
      cancer progression. 

PMID- 26316946
TI  - Analysis of Expression of Vascular Endothelial Growth Factor A and Hypoxia
      Inducible Factor-1alpha in Patients Operated on Stage I Non-Small-Cell Lung
      Cancer.
AB  - Objectives. Recent studies show that expression of hypoxia inducible factor
      1alpha (HIF-1alpha) favours expression of vascular endothelial growth factor A
      (VEGF-A), and these biomarkers are linked to cellular proliferation,
      angiogenesis, and metastasis in different cancers. We analyze expression of HIF
      1alpha and VEGF-A to clinicopathologic features and survival of patients operated
      on stage I non-small-cell lung cancer. Methodology. Prospective study of 52
      patients operated on with stage I. Expression of VEGF-A and HIF-1alpha was
      performed through real-time quantitative polymerase chain reaction (qRT-PCR).
      Results. Mean age was 64.7 and 86.5% of patients were male. Stage IA represented
      23.1% and stage IB 76.9%. Histology classification was 42.3% adenocarcinoma,
      34.6% squamous cell carcinoma, and 23.1% others. Median survival was 81.0 months
      and 5-year survival 67.2%. There was correlation between HIF-1alpha and VEGF-A (P
      = 0.016). Patients with overexpression of HIF-1alpha had a tendency to better
      survival with marginal statistical significance (P = 0.062). Patients with
      overexpression of VEGF-A had worse survival, but not statistically significant (P
      = 0.133). Conclusion. The present study revealed that VEGF-A showed correlation
      with HIF-1alpha. HIF-1alpha had a tendency to protective effect with a P value
      close to statistical significance. VEGF-A showed a contrary effect but without
      statistical significance. 

PMID- 26316947
TI  - Heavy Metal Content in Thoracic Tissue Samples from Patients with and without
      NSCLC.
AB  - Objectives. Environmental factors expose an individual to heavy metals that may
      stimulate cancer growth preclinically including non-small cell lung cancer
      (NSCLC) cells. Here, we examine the prevalence of four heavy metals present in
      postsurgical tissues from individuals with and without NSCLC. Materials and
      Methods. Thoracic tissue samples from two separate sample sets were analyzed for
      cadmium (Cd), arsenic (As), mercury (Hg), and lead (Pb) content. Results. In the
      first sample set, there was no significant measurable amount of Pb and Hg found
      in either NSCLC tissue or nonmalignant lung tissue samples. Cd was the most
      prevalent heavy metal and As was present in moderate amounts. In the second
      sample set, Cd was measurable across all tissue types taken from 28 NSCLC
      patients and significantly higher Cd was measurable in noncancer benign lung (n =
      9). In the NSCLC samples, As was measurable in moderate amounts, while Hg and Pb
      amounts were negligible. Conclusion. Cd and As are present in lung tissues for
      patients with NSCLC. With existing preclinical evidence of their tumorigenecity,
      it is plausible that Cd and/or As may have an impact on NSCLC development.
      Additional studies examining the prevalence and association between smokers and
      nonsmokers are suggested. 

PMID- 26316948
TI  - Association between Argyrophilic Proteins of Nucleolar Organizer Regions,
      Clinicomorphological Parameters, and Survival in Non-Small-Cell Lung Cancer.
AB  - We studied argyrophilic proteins associated with nucleolar organizer regions
      (AgNOR) in non-small-cell cancer. We determined the area index (AI) and
      coefficient of variation (CV) of AgNOR. AI is associated with the key
      clinicomorphological parameters within the TNM system: T and N values, greatest
      tumor dimension up to 3 cm and more, disease stage, histogenesis, and tumor
      differentiation. CV is associated with T value, greatest tumor dimension up to 3
      cm and more, histogenesis, and tumor differentiation. Survival of patients is
      longer in low AI or CV values versus high AI or CV values, longer in low AI and
      CV values (-AI/-CV type), shorter in high AI and CV values (+AI/+CV type), and
      intermediate in opposite AI and CV values (-AI/+CV and +AI/-CV types).
      Independent predictors in non-small-cell lung cancer include N value, greatest
      tumor dimension, histogenesis, and CV. Assessment of quantitative values and
      heterogeneity of AgNOR is important for differential diagnosis and prognosis of
      non-small-cell lung cancer. 

PMID- 26316949
TI  - Chemotherapy Treatment of Elderly Patients (>=70 Years) with Non-Small Cell Lung
      Cancer: A Seven-Year Retrospective Study of Real-Life Clinical Practice at
      Karolinska University Hospital, Sweden.
AB  - An increasing proportion of cancer patients are aged >65 years and many are aged
      >70 years. Treatment of the elderly with lung cancer has, therefore, become an
      important issue; so we performed a retrospective study of our patients to
      demonstrate how elderly patients with NSCLC are treated in real-life, clinical
      practice. All patients aged >=70 years with NSCLC at our department were reviewed
      retrospectively. In total, 1059 patients (50.8% of all NSCLC patients). Of these
      patients, 243 (22.9%) received chemotherapy, 164 (70.4%) of whom were treated
      with a platinum doublet using carboplatin. Second- and third-line chemotherapy
      were given to 31.4% and 13.9% of patients, respectively. Median overall survival
      was 289 and 320 days for male and female patients, respectively. Patients with
      performance status (PS) 0 experienced significantly better survival than patients
      with PS1 or PS 2: 410, 314, and 204 days, respectively. Age was of less
      importance, with patients aged 70-79 years versus those aged >=80 years.
      Treatment of elderly NSCLC patients with chemotherapy is feasible if they have a
      good PS and appears to prolong survival. In this study, we found no significant
      differences in survival either between age groups or genders. 

PMID- 26316950
TI  - Malignant Pleural Mesothelioma Outcomes in the Era of Combined Platinum and
      Folate Antimetabolite Chemotherapy.
AB  - Introduction. Malignant pleural mesothelioma (MPM) is associated with a poor
      prognosis. Palliative platinum-based chemotherapy may help to improve symptoms
      and prolong life. Since 2004, the platinum is commonly partnered with a folate
      antimetabolite. We performed a review investigating if survival had significantly
      changed before and after the arrival of folate antimetabolites in clinical
      practice. Methods. All MPM patients from January 1991 to June 2012 were
      identified. Data collected included age, gender, asbestos exposure, presenting
      signs/symptoms, performance status, histology, stage, bloodwork, treatment
      modalities including chemotherapy, and date of death or last follow-up. The
      primary endpoint was overall survival. Cox models were applied to determine
      variables associated with survival. Results. There were 245 patients identified.
      Median overall survival for all patients was 9.4 months. After multivariate
      analysis, performance status, stage, histology, leucocytosis, and thrombophilia
      remained independently associated with survival. Among all patients who received
      chemotherapy, there was no difference in overall survival between the periods
      before and after folate antimetabolite approval: 14.2 versus 13.2 months (P =
      0.35). Specifically receiving combined platinum-based/folate antimetabolite
      chemotherapy did not improve overall survival compared to all other chemotherapy
      regimens: 14.1 versus 13.6 months (P = 0.97). Conclusions. In this review, we did
      not observe an incremental improvement in overall survival after folate
      antimetabolites became available. 

PMID- 26316951
TI  - Factors Associated with Use of Latex Condom-Compatible Lubricants by Men Who Have
      Sex with Men in India: Implications for HIV Prevention.
AB  - We examined the prevalence and type of rectal lubricants use and factors
      associated with exclusive use of latex-condom compatible lubricants (water-based
      lubricants) among men who have sex with men (MSM) using data from a large-scale
      cross-sectional survey conducted in 2009/10 in three Indian states. Using time
      location cluster sampling, 3880 MSM were recruited from cruising sites. We used
      multiple logistic regression to assess the association between type of lubricants
      used and sociodemographic and programmatic indicators. Among those who reported
      using lubricants (64%) more than half (53%) exclusively used water-based
      lubricants, less than one-tenth used exclusively oil-based lubricants, and nearly
      40% used both water-based and oil-based lubricants. Factors associated with
      exclusive use of water-based lubricants were exposure to HIV prevention
      interventions (AOR: 6.18, 95% CI 4.82 to 7.92) and kothi-identified MSM
      feminine/anal-receptive (AOR: 2.56, 95% CI 2.12 to 3.10). Targeted HIV
      interventions among MSM need to promote and distribute latex condom-compatible
      lubricants for use during anal sex-irrespective of their presumed or stated
      sexual role in anal sex, and educate them not to use oil-based lubricants with
      condoms. 

PMID- 26316952
TI  - Measurement of Stigma in Men Who Have Sex with Men in Hanoi, Vietnam: Assessment
      of a Homosexuality-Related Stigma Scale.
AB  - Objective. To develop and assess a homosexuality-related stigma scale among men
      who have sex with men (MSM) in Hanoi, Vietnam. Methods. We conducted a cross
      sectional study using respondent-driven sampling in Hanoi, Vietnam, in 2011. We
      used a cross-validation approach. Factor analysis was performed, and interitem
      correlation matrices were constructed to identify the latent factor structures,
      examine the goodness of fit, and assess convergent and discriminant validity of
      the determined scales. Internal consistency checks were performed in split
      samples and whole sample, and separately for each determined factor. Results. The
      findings were consistent in split samples. Three homosexuality-related stigma
      factors were identified: enacted homosexual stigma, perceived homosexual stigma,
      and internalized homosexual stigma. The fit indices of the confirmatory factor
      analysis in both split samples supported the hypothesized three-factor structures
      (in subsamples A and B: chi (2)/degrees of freedom ratio = 1.77 and 1.59,
      nonnormed fit index = 0.92 and 0.94, comparative fit index = 0.93 and 0.95, and
      the root mean square of approximation = 0.06 and 0.05, resp.). The interitem
      correlation supported the convergent and discriminant validity of the scales. The
      reliability of the three scales indicated good consistency (Cronbach's alpha:
      0.79-0.84) across split samples and for the whole data. Conclusion. Our scales
      have good psychometric properties for measuring homosexuality-related stigma.
      These comprehensive and practical tools are crucial not only to assess stigma
      against MSM and its consequence, but also to guide the development of
      interventions targeting MSM, as well as to evaluate the efficacy of existing
      stigma reduction efforts in Vietnam and other countries with similar settings. 

PMID- 26316954
TI  - Genital Ulcer Disease: How Worrisome Is It Today? A Status Report from New Delhi,
      India.
AB  - Background and Objectives. Genital ulcer diseases represent a diagnostic dilemma,
      especially in India, where few STI clinics have access to reliable laboratory
      facility. The changing STI trends require that a correct diagnosis be made in
      order to institute appropriate treatment and formulate control policies. The
      objective of this study was to determine recent trends in aetiology of genital
      ulcers, by using accurate diagnostic tools. Methods. Specimens from 90 ulcer
      patients were processed for dark field microscopy, stained smears, culture for H.
      ducreyi, and real-time PCR. Blood samples were collected for serological tests.
      Results. Prevalence of GUD was 7.45 with mean age at initial sexual experience as
      19.2 years. Use of condom with regular and nonregular partners was 19.5% and
      42.1%, respectively. Sexual orientation was heterosexual (92.2%) or homosexual
      (2.2%). There were 8 cases positive for HIV (8.9%). Herpes simplex virus ulcers
      were the commonest, followed by syphilis and chancroid. There were no cases of
      donovanosis and LGV. Conclusions. A valuable contribution of this study was in
      validating clinical and syndromic diagnoses of genital ulcers with an accurate
      aetiological diagnosis. Such reliable data will aid treatment and better define
      control measures of common agents and help eliminate diseases amenable to
      elimination, like donovanosis. 

PMID- 26316955
TI  - Rapid-Testing Technology and Systems Improvement for the Elimination of
      Congenital Syphilis in Haiti: Overcoming the "Technology to Systems Gap".
AB  - Background. Despite the availability of rapid diagnostic tests and inexpensive
      treatment for pregnant women, maternal-child syphilis transmission remains a
      leading cause of perinatal morbidity and mortality in developing countries. In
      Haiti, more than 3000 babies are born with congenital syphilis annually. Methods
      and Findings. From 2007 to 2011, we used a sequential time series, multi
      intervention study design in fourteen clinics throughout Haiti to improve
      syphilis testing and treatment in pregnancy. The two primary interventions were
      the introduction of a rapid point-of-care syphilis test and systems strengthening
      based on quality improvement (QI) methods. Syphilis testing increased from 91.5%
      prediagnostic test to 95.9% after (P < 0.001) and further increased to 96.8% (P <
      0.001) after the QI intervention. Despite high rates of testing across all time
      periods, syphilis treatment lagged behind and only increased from 70.3% to 74.7%
      after the introduction of rapid tests (P = 0.27), but it improved significantly
      from 70.2% to 84.3% (P < 0.001) after the systems strengthening QI intervention.
      Conclusion. Both point-of-care diagnostic testing and health systems-based
      quality improvement interventions can improve the delivery of specific evidence
      based healthcare interventions to prevent congenital syphilis at scale in Haiti.
      Improved treatment rates for syphilis were seen only after the use of systems
      based quality improvement approaches. 

PMID- 26316953
TI  - The Role of Sexually Transmitted Infections in HIV-1 Progression: A Comprehensive
      Review of the Literature.
AB  - Due to shared routes of infection, HIV-infected persons are frequently coinfected
      with other sexually transmitted infections (STIs). Studies have demonstrated the
      bidirectional relationships between HIV and several STIs, including herpes
      simplex virus-2 (HSV-2), hepatitis B and C viruses, human papilloma virus,
      syphilis, gonorrhea, chlamydia, and trichomonas. HIV-1 may affect the clinical
      presentation, treatment outcome, and progression of STIs, such as syphilis, HSV
      2, and hepatitis B and C viruses. Likewise, the presence of an STI may increase
      both genital and plasma HIV-1 RNA levels, enhancing the transmissibility of HIV
      1, with important public health implications. Regarding the effect of STIs on HIV
      1 progression, the most studied interrelationship has been with HIV-1/HSV-2
      coinfection, with recent studies showing that antiherpetic medications slow the
      time to CD4 <200 cells/uL and antiretroviral therapy among coinfected patients.
      The impact of other chronic STIs (hepatitis B and C) on HIV-1 progression
      requires further study, but some studies have shown increased mortality rates.
      Treatable, nonchronic STIs (i.e., syphilis, gonorrhea, chlamydia, and
      trichomonas) typically have no or transient impacts on plasma HIV RNA levels that
      resolve with antimicrobial therapy; no long-term effects on outcomes have been
      shown. Future studies are advocated to continue investigating the complex
      interplay between HIV-1 and other STIs. 

PMID- 26316956
TI  - Adverse Psychosexual Impact Related to the Treatment of Genital Warts and
      Cervical Intraepithelial Neoplasia.
AB  - Objective. To compare the psychosexual impact related to the treatment of genital
      warts and cervical intraepithelial neoplasia (CIN) in women. Methods. 75 patients
      presenting with HPV-induced genital lesions, belonging to one of two patient
      groups, were included in the study: 29 individuals with genital warts (GWs) and
      46 individuals with CIN grades 2 or 3 (CIN 2/3). Initially, medical charts of
      each woman were examined for extraction of data on the type of HPV-induced
      infection and treatment administered. Subjects were interviewed to collect
      sociodemographic data as well as personal, gynecologic, obstetric, and sexual
      history. After this initial anamnesis, the Sexual Quotient-Female Version (SQ-F)
      questionnaire was applied to assess sexual function. After application of the
      questionnaire, patients answered specific questions produced by the researchers,
      aimed at assessing the impact of the disease and its treatment on their sexual
      lives. Results. It is noteworthy that patients with CIN 2/3 had statistically
      similar classification of sexual quotient to patients with GWs (P = 0.115).
      However, patients with GWs more frequently gave positive answers to the specific
      questions compared to patients with CIN 2/3. Conclusion. Based on these findings,
      it is clear that GWs have a greater impact on sexual behavior compared to CIN
      2/3. 

PMID- 26316957
TI  - Sexually Transmitted Infections in Women Participating in a Biomedical
      Intervention Trial in Durban: Prevalence, Coinfections, and Risk Factors.
AB  - Background. Sexually transmitted infections (STIs) continue to be a significant
      public health problem especially among women of reproductive age in Africa.
      Methods. A total of 2236 women that had enrolled in the MDP301 vaginal
      microbicide trial were tested for the presence of Chlamydia trachomatis (CT),
      Neisseria gonorrhea (NG), Treponema pallidum, and Trichomonas vaginalis (TV).
      Results. CT was identified as the most prevalent STI (11%) followed by TV (10%),
      NG, and Syphilis (3%). The highest prevalence of coinfection was reported between
      T. pallidum and TV (19.67%, P = 0.004), followed by CT and TV (13.52%, P <=
      0.001). Risk factors that were significantly associated with STI acquisition were
      women of 23 years of age or younger (HR: 1.50, 95% CI 1.17, 1.93), baseline STI
      with CT (HR: 1.77, 95% CI 1.32, 2.35), TV (HR: 1.58, 95% CI, 1.20, 2.10), and T.
      pallidum (HR: 5.13, 95% CI 3.65, 7.22), and a low education level (HR: 1.30, 95%
      CI 1.02, 1.66). Conclusion. Young women with lower education and a history of
      STIs are at high risk of multiple STIs. Prevention programs should consider
      target approach to STI prevention among young women. This trial is registered
      with ISRCTN64716212. 

PMID- 26316958
TI  - Assessment of Sexual and Reproductive Health Status of Street Children in Addis
      Ababa.
AB  - Street children worldwide do not have the information, skills, health services,
      and support they need to go through sexual development during adolescence. This
      study is undertaken to systematically investigate the fit between street
      children's sexual and reproductive health needs and the existing services. A
      cross-sectional study was conducted among 422 street children and four service
      providers. About 72.5% of the respondents were sexually active during data
      collection and 84.3% of males and 85.7% of females tended to have multiple sexual
      partners. More than two-thirds (67.3%) of the participants had used at least one
      type of substance. History of substance use (OR = 2.5; 95% CI = 1.42-4.56) and
      being on the street for the first one to three years (OR = 5.9; 95% CI = 1.41
      7.22) increased the likelihood of having sexual activity. More than half (64.9%)
      of the street children did not attend any kind of sexual or reproductive health
      education programs. Lack of information on available services (26.5%) was the
      biggest barrier for utilization of local sexual and reproductive health services.
      From the individual interview with coordinator, the financial and networking
      problems were hindering the service delivery for street children. In conclusion,
      street children who are special high risk group have not been targeted and hence
      continue to remain vulnerable and lacking in sexual and reproductive health
      services and sexual health services are poorly advertised and delivered to them. 

PMID- 26316959
TI  - Dual Protection and Dual Methods in Women Living with HIV: The Brazilian Context.
AB  - The cooccurrence of HIV and unintended pregnancy has prompted a body of work on
      dual protection, the simultaneous protection against HIV and unintended
      pregnancy. This study examines dual protection and dual methods as a risk
      reduction strategy for women living with HIV. Data are from a cross-sectional
      sample of HIV-positive women attended in Specialized STI/AIDS Public Health
      Service Clinics in 13 municipalities from all five regions of Brazil 2003-2004 (N
      = 834). Descriptive techniques and logistic regression were used to examine dual
      protection among women living with HIV. We expand the definition of dual
      protection to include consistent condom use and reversible/irreversible
      contraceptive methods, we test the dual methods hypothesis that women who use
      dual methods will use condoms less consistently than women who use only condoms,
      and we identify predictors of dual protection. Dual protection is common in our
      sample. Women who use dual methods have lower odds of consistent condom use than
      women who only use condoms. Among dual method users, we find that women who use
      an irreversible method use condoms more consistently than women who use a
      reversible method. Women on ART and with an HIV-serodiscordant partner have
      greater odds of consistent condom use than their counterparts. 

PMID- 26316960
TI  - Serosorting and HIV/STI Infection among HIV-Negative MSM and Transgender People:
      A Systematic Review and Meta-Analysis to Inform WHO Guidelines.
AB  - We conducted a systematic review and meta-analysis to assess the association
      between serosorting and HIV infection, sexually transmitted infections (STIs),
      and quality of life among men who have sex with men (MSM) and transgender people.
      Two reviewers independently screened abstracts and abstracted data. Meta-analyses
      were conducted using random effects models. Of 310 citations reviewed, 4
      observational studies, all with MSM, met inclusion criteria. Compared to
      consistent condom use, serosorting was associated with increased risk of HIV (3
      studies, odds ratio (OR): 1.80, 95% confidence interval (CI):1.21-2.70) and
      bacterial STIs (1 study, OR: 1.62, 95% CI: 1.44-1.83). Compared to no condom use,
      serosorting was associated with reduced risk of HIV (3 studies, OR: 0.46, 95% CI:
      0.25-0.83) and bacterial STIs (1 study, OR: 0.81, 95% CI: 0.73-0.91). Among HIV
      negative MSM, condom use appears to be more protective against HIV and STIs than
      serosorting and should be encouraged. However, serosorting may be better than no
      condom use as a harm reduction strategy. 

PMID- 26316961
TI  - Epidemiology of Sexually Transmitted Infections among Human Immunodeficiency
      Virus Positive United States Military Personnel.
AB  - Background. Minimal data exist that describe the epidemiology of sexually
      transmitted infections (STI) in human immunodeficiency virus (HIV) positive
      populations across the pre- and post-diagnosis periods for HIV. Purpose. The
      purpose of this study was to identify and describe the epidemiology of gonorrhea,
      chlamydia, syphilis, herpes simplex virus, and human papillomavirus in an HIV
      positive population. Methods. All 1,961 HIV seropositive United States active
      duty military personnel from 2000-2010 were identified. STI diagnoses relative to
      HIV diagnosis from 1995, which was the earliest electronic medical record
      available, to 2010 were examined. Results. The incidence diagnosis rates of STI
      generally increased during the period leading up to eventual HIV diagnosis. The
      rates of STI during the post-HIV diagnosis period fluctuated, but remained
      elevated compared to pre-HIV diagnosis period. Approximately 45%-69% with an STI
      in the HIV seropositive military population were diagnosed with their first STI
      greater than one year after their HIV diagnosis. Of those who were diagnosed with
      an STI in the post-HIV diagnosis period, 70.6% had one STI diagnosis, 23.5% had
      two STI diagnoses, and 5.8% had three or more STI diagnoses. Conclusions. Despite
      aggressive counseling, high-risk sexual behavior continues to occur in the HIV
      positive military population. 

PMID- 26316962
TI  - Investigating Recent Testing among MSM: Results from Community-Based HIV Rapid
      Testing Attendees in France.
AB  - Background. We aimed to identify factors associated with recent HIV testing in
      MSM who attended two experimental community-based and nonmedicalized voluntary
      counselling and testing programmes (CB-VCT) targeting MSM in France. Methods.
      This analysis was based on data collected in 2009-2011 through a self
      administered pretesting questionnaire. An index measuring the level of
      participants' sexual orientation disclosure was built: the higher the index, the
      greater the disclosure. Factors associated with recent HIV testing (last test <=
      1 year) were identified using a multivariate logistic regression model adjusted
      for the CB-VCT programme of enrolment. Results. 716 MSM provided data on testing
      history. Overall, 49% were recently tested for HIV and 51% were not. Recently
      tested MSM had a higher homosexuality disclosure index (adjusted OR [95%
      confidence interval]: aOR = 1.2 [1.1-1.4]), reported more inconsistent condom use
      during anal sex with men (aOR = 1.6 [1.2-2.1]), and were less likely to have sex
      under the influence of club drugs (aOR = 0.6 [0.4-1.0]). Conclusion. New testing
      strategies should focus on those who live their homosexuality relatively secretly
      and those who use club drugs before sex. Governments should develop policies
      which encourage improved social acceptance of homosexuality as concealment of
      sexual orientation represents a major barrier to testing. 

PMID- 26316963
TI  - The Impact of Integration of Rapid Syphilis Testing during Routine Antenatal
      Services in Rural Kenya.
AB  - We evaluated the integration of rapid syphilis tests (RSTs) and penicillin
      treatment kits into routine antenatal clinic (ANC) services in two rural
      districts in Nyanza Province, Kenya. In February 2011, nurses from 25 clinics
      were trained in using RSTs and documenting test results and treatment. During
      March 2011-February 2012, free RSTs and treatment kits were provided to clinics
      for use during ANC visits. We analyzed ANC registry data from eight clinics
      during the 12-month periods before and during RST program implementation and
      compared syphilis testing, diagnosis, and treatment during the two periods.
      Syphilis testing at first ANC visit increased from 18% (279 of 1,586 attendees)
      before the intervention to 70% (1,123 of 1,614 attendees) during the intervention
      (P < 0.001); 35 women (3%) tested positive during the intervention period
      compared with 1 (<1%) before (P < 0.001). Syphilis treatment was not recorded
      according to training recommendations; seven clinics identified 28 RST-positive
      women and recorded 34 treatment kits as used. Individual-level data from three
      high-volume clinics supported that the intervention did not negatively affect HIV
      test uptake. Integrating RSTs into rural ANC services increased syphilis testing
      and detection. Record keeping on treatment of syphilis in RST-positive women
      remains challenging. 

PMID- 26316964
TI  - The Epidemiology of Herpes Simplex Virus Type-2 Infection among Pregnant Women in
      Rural Mysore Taluk, India.
AB  - Objectives. To assess the prevalence and determinants of herpes simplex virus
      type 2 (HSV-2) infections among pregnant women attending mobile antenatal health
      clinic in rural villages in Mysore Taluk, India. Methods. Between January and
      September 2009, 487 women from 52 villages participated in this study. Each
      participant consented to provide a blood sample for HSV-2 and HIV testing and
      underwent an interviewer-administered questionnaire. Results. HSV-2 prevalence
      was 6.7% (95% confidence interval (CI) 4.4-9.0), and one woman tested positive
      for HIV. The median age of women was 20 years and 99% of women reported having a
      single lifetime sex partner. Women whose sex partner traveled away from home had
      2.68 (CI: 1.13-6.34) times the odds of being HSV-2 seropositive compared to women
      whose sex partner did not travel. Having experienced genital lesions was also
      associated with HSV-2 infection (P value = 0.08). Conclusion. The 6.7% HSV-2
      prevalence was similar to results obtained in studies among pregnant women in
      other parts of India. It appeared that most women in this study contracted HSV-2
      from their spouses and few regularly used condoms. This finding highlights the
      need for public health policies to increase awareness and education about
      prevention methods among women and men living in rural India. 

PMID- 26316965
TI  - Remembering the Children: Implementation and Success of a Robust Method for
      Identifying and Testing Children of HIV Patients.
AB  - Background. Children of HIV patients are a historically neglected demographic by
      HIV services. It has been recommended by CHIVA that HIV services have a robust
      method of detecting and testing untested children. We note that no such method is
      either in widespread use or in the literature. Method. In December 2011, a one
      page proforma to identify HIV untested children and a clear multidisciplinary
      pathway to test them were implemented. Twelve months later the uptake of the
      proforma and pathway, the numbers of patients and children identified for
      testing, and their outcomes were audited. Results. The proforma was completed in
      192/203 (94.6%) eligible patients. Twenty-five (21.5%) of 118 identified
      offspring had not been tested. Ten (8.5%) of these were <18 years old. All were
      reported to be clinically well. Ten children were referred for testing, seven
      were tested immediately, and three were tested within 18 months of
      identification. All children were tested HIV negative. Discussion. We have
      identified a method of identification that is easy and robust and provides a user
      friendly safety net to empower healthcare providers to identify and test children
      at risk. We recommend the implementation of such strategies nationwide to prevent
      death due to undiagnosed HIV in children. 

PMID- 26316966
TI  - Clinical Spectrum of Oral Secondary Syphilis in HIV-Infected Patients.
AB  - Background. Oral lesions may constitute the first clinical manifestation in
      secondary syphilis, but detailed descriptions in HIV-infected individuals are
      scarce. Objective. To describe the clinical characteristics of oral secondary
      syphilis in HIV-infected patients and its relevance in the early diagnosis of
      syphilis. Methods. Twenty HIV/AIDS adult subjects with oral secondary syphilis
      lesions presenting at two HIV/AIDS referral centers in Mexico City (2003-2011)
      are described. An oral examination was performed by specialists in oral pathology
      and medicine; when possible, a punch biopsy was done, and Warthin-Starry stain
      and immunohistochemistry were completed. Intraoral herpes virus infection and
      erythematous candidosis were ruled out by cytological analysis. Diagnosis of oral
      syphilis was confirmed with positive nontreponemal test (VDRL), and, if possible,
      fluorescent treponemal antibody test. Results. Twenty male patients (median age
      31.5, 21-59 years) with oral secondary syphilis lesions were included. Oral
      lesions were the first clinical sign of syphilis in 16 (80%) cases. Mucous patch
      was the most common oral manifestation (17, 85.5%), followed by shallow ulcers
      (2, 10%) and macular lesions (1, 5%). Conclusions. Due to the recent rise in HIV
      syphilis coinfection, dental and medical practitioners should consider secondary
      syphilis in the differential diagnosis of oral lesions, particularly in HIV
      infected patients. 

PMID- 26316967
TI  - HPV Infection in a Cohort of HIV-Positive Men and Women: Prevalence of Oncogenic
      Genotypes and Predictors of Mucosal Damage at Genital and Oral Sites.
AB  - The aim of this study was to assess the prevalence of HPV infection and
      determinants of abnormal cytology in HIV-positive patients. In a cross-sectional
      study, patients of both sexes, asymptomatic for HPV, underwent anorectal
      (men)/cervical (women) and oral swabs. Cytology and HPV-PCR detection/genotyping
      (high- and low-risk genotypes, HR-LR/HPV) were performed. A total of 20% of the
      277 enrolled patients showed oral HPV, with no atypical cytology; in men, anal
      HPV prevalence was 81% with 64% HR genotypes. In women, cervical HPV prevalence
      was 58% with 37% HR-HPV. The most frequent genotypes were HPV-16 and HPV-18; 37%
      of men and 20% of women harbored multiple genotypes. Also, 47% of men showed anal
      squamous intraepithelial lesions (SILs); 6% had high- and 35% low-grade SILs
      (HSILs/LSILs); 5% had atypical squamous cells of undetermined significance (ASC
      US). HR-HPV was independently associated with anal-SIL in men (P = 0.039).
      Moreover, 37% of women showed cervical SIL: 14 ASC-US, 15 LSILs, 4 HSILs, and 1
      in situ cancer. The presence of both LR and HR-HPV in women was independently
      associated with SIL (P = 0.003 and P = 0.0001). HR-HPV and atypical cytology were
      frequently identified in our cohort. HPV screening should be mandatory in HIV
      infected subjects, and vaccine programs for HPV-negative patients should be
      implemented. 

PMID- 26316968
TI  - Access to Basic HIV-Related Services and PrEP Acceptability among Men Who Have
      sex with Men Worldwide: Barriers, Facilitators, and Implications for Combination
      Prevention.
AB  - Introduction. Men who have sex with men (MSM) are disproportionately impacted by
      HIV globally. Easily accessible combination HIV prevention strategies, tailored
      to the needs of MSM, are needed to effectively address the AIDS pandemic. Methods
      and Materials. We conducted a cross-sectional study among MSM (n = 3748) from 145
      countries from April to August 2012. Using multivariable random effects models,
      we examined factors associated with acceptability of preexposure prophylaxis
      (PrEP) and access to condoms, lubricants, HIV testing, and HIV treatment.
      Results. Condoms and lubricants were accessible to 35% and 22% of all
      respondents, respectively. HIV testing was accessible to 35% of HIV-negative
      respondents. Forty-three percent of all HIV-positive respondents reported that
      antiretroviral therapy was easily accessible. Homophobia, outness, and service
      provider stigma were significantly associated with reduced access to services.
      Conversely, community engagement, connection to gay community, and comfort with
      service providers were associated with increased access. PrEP acceptability was
      associated with lower PrEP-related stigma, less knowledge about PrEP, less
      outness, higher service provider stigma, and having experienced violence for
      being MSM. Conclusions. Ensuring HIV service access among MSM will be critical in
      maximizing the potential effectiveness of combination approaches, especially
      given the interdependence of both basic and newer interventions like PrEP.
      Barriers and facilitators of HIV service access for MSM should be better
      understood and addressed. 

PMID- 26316969
TI  - Community-Based Surveys for Determining the Prevalence of HIV, Chlamydia, and
      Gonorrhoea in Men Having Sex with Men in Hong Kong.
AB  - Background. Community sampling of men having sex with men (MSM) for human
      immunodeficiency virus (HIV) and sexually transmitted infections prevalence
      studies poses challenges in view of problems in logistics and the hidden nature
      of MSM population. Methods. MSM in Hong Kong were recruited through social venues
      and the Internet. All participants were invited to complete a behavioural
      questionnaire and submit a urine specimen for HIV, Chlamydia, and gonorrhoea
      testing. Results. Totally, 994 MSM were recruited. No differences between venue
      and online-recruited respondents were identified regarding their demographics and
      infection status. The prevalence of HIV, Chlamydia, and gonorrhoea was 3.6% (95%
      CI: 2.6-5.0%), 4.7% (95% CI: 3.6-6.2%), and 0.2% (95% CI: 0.1-0.7%),
      respectively. Of all HIV cases, only 8.3% were aware of the infection; reflecting
      newly infected MSM were probably overrepresented. Some 58.3% had had HIV test
      within the past year, and 11.1% had CT/NG coinfection. HIV infection was
      associated with group sex [aOR: 2.67 (1.03-6.92)], receiving money for anal sex
      [aOR: 4.63 (1.12-19.18)], and unprotected anal sex with nonregular partners [aOR:
      3.047 (1.16-8.01)]. Conclusion. Difference between venue- and online-recruited
      MSM was observed. A combination of sampling methods is complementary for
      epidemiology purpose. Overall, risk behaviours practised by undiagnosed HIV
      positive MSM remains a cause for concern. 

PMID- 26316970
TI  - Pharyngeal Gonorrhoea in Women: An Important Reservoir for Increasing Neisseria
      gonorrhoea Prevalence in Urban Australian Heterosexuals?
AB  - We aim to characterize sexual behavioral aspects of heterosexual Neisseria
      gonorrhoea (NG) acquisition in two Sexually Transmitted Diseases clinics in
      Sydney, Australia, in 2008-2012. Of 167 NG cases, 102 were heterosexually
      acquired with a trend of increasing NG prevalence in heterosexuals from 1.1% (95%
      CI 0.6-2.1) in 2008 to 3.0% (95% CI 2.0-4.0) in 2012 (P = 0.027). Of heterosexual
      male cases, unprotected fellatio was the likely sexual activity for NG
      acquisition in 21/69 (30.4%) and commercial sex work (CSW) contact the likely
      source in 28/69 (40.6%). NG prevalence overall in CSW (2.2%) was not
      significantly higher than in non-CSW (1.2%) (P = 0.15), but in 2012 there was a
      significant increase in NG prevalence in CSW (8.6%) compared to non-CSW (1.6%) (P
      < 0.001). Pharyngeal NG was found in 9/33 (27.3%) female cases. Decreased
      susceptibility to ceftriaxone (MIC >= 0.03 mg/L) occurred in 2.5% NG isolates,
      none heterosexually acquired. All were azithromycin susceptible. A significant
      trend of increasing prevalence of heterosexual gonorrhoea in an urban Australian
      STD clinic setting is reported. We advocate maintenance of NG screening in women,
      including pharyngeal screening in all women with partner change who report
      fellatio, as pharyngeal NG may be an important reservoir for heterosexual
      transmission. Outreach to CSW should be enhanced. 

PMID- 26316971
TI  - Increasing Antenatal Care and HIV Testing among Rural Pregnant Women with
      Conditional Cash Transfers to Self-Help Groups: An Evaluation Study in Rural
      Mysore, India.
AB  - Background. We describe a one-year evaluation study comparing SCIL intervention
      of mobile provision of integrated ANC/ HIV testing with an enhanced (SCIL+)
      intervention of community mobilization strategy providing conditional cash
      transfers (CCT) to women's SHG for identifying and accompanying pregnant women to
      mobile clinics. Methods. Twenty pairs of villages matched on population,
      socioeconomic status, access to medical facilities, and distance from Mysore city
      were divided between SCIL and SCIL+ interventions. The primary study outcome was
      the proportion of total pregnancies in these villages who received ANC and HIV
      testing. Results. Between April 2011 and March 2012, 552 pregnant women
      participated in SCIL or SCIL+ interventions. Among women who were pregnant at the
      time of intervention delivery, 181 of 418 (43.3%) women pregnant at the time of
      intervention delivery received ANC in the SCIL arm, while 371 of 512 (72.5%)
      received ANC in the SCIL+ arm (P < 0.001); 175 (97%) in the SCIL and 366 (98.6%)
      in the SCIL+ arm consented to HIV testing (P < 0.001). HIV prevalence of 0.6% was
      detected among SCIL clinic, and 0.9% among attending SCIL+ clinic attendees.
      Conclusion. Provision of CCT to women's microeconomic SHG appears to
      significantly increase uptake of ANC/HIV testing services in rural Mysore
      villages. 

PMID- 26316972
TI  - Sexual Transmission of HCV in Heterologous Monogamous Spouses.
AB  - We screened for evidence of HCV infection in healthy heterologous monogamous
      spouses of chronic HCV patients and studied the relation with various risk
      factors. A cross-sectional study of fifty healthy monogamous heterosexual spouses
      of HCV-positive index cases was carried out. All participants were HBV and HIV
      negative. The association with various risk factors was studied. Five spouses
      (10%) showed evidence of HCV infection. Two partners were positive for HCV
      antibody alone (4%) and 3 for antibody and HCV PCR (6%). No association was found
      between HCV infection and various sociodemographic parameters with the exception
      of older age categories. Intraspousal transmission of HCV may be an important
      source of spread of HCV infection. The reservoir of HCV-infected individuals in
      Egypt is sizable, and sexual transmission of HCV may contribute to the total
      burden of infection in Egypt. 

PMID- 26316973
TI  - Care Seeking Behaviour and Barriers to Accessing Services for Sexual Health
      Problems among Women in Rural Areas of Tamilnadu State in India.
AB  - Background. Sexually transmitted infections (STIs) may be either asymptomatic or
      symptomatic. Regardless of the presence or absence of symptoms all STIs can lead
      to major complications if left untreated. Objective. To assess the care seeking
      behaviour and barriers to accessing services for sexual health problems among
      young married women in rural areas of Thiruvarur district of Tamil Nadu state in
      India. Methods. A community based cross-sectional study was conducted in 28
      villages selected using multistage sampling technique for selecting 605 women in
      the age group of 15-24 years during July 2010-April 2011. Results. The prevalence
      rate of reproductive tract infections (RTIs) and STIs was observed to be 14.5%
      and 8.8%, respectively, among the study population. Itching/irritation over
      vulva, thick white discharge, discharge with unpleasant odor, and frequent and
      uncomfortable urination were most commonly experienced symptoms of sexual health
      problems. Around three-fourth of the women received treatment for sexual health
      problems. Perception of symptoms as normal, feeling shy, lack of female health
      workers, distance to health facility, and lack of availability of treatment were
      identified as major barriers for not seeking treatment for RTIs/STIs. Conclusion.
      Family tradition and poor socioeconomic conditions of the family appear to be the
      main reasons for not utilizing the health facility for sexual health problems.
      Integrated approach is strongly suggested for creating awareness to control the
      spread of sexual health problems among young people. 

PMID- 26316974
TI  - Young Risk Takers: Alcohol, Illicit Drugs, and Sexual Practices among a Sample of
      Music Festival Attendees.
AB  - Background. Alcohol and other drug use and sexual risk behaviour are increasing
      among young Australians, with associated preventable health outcomes such as
      sexually transmissible infections (STIs) on the rise. Methods. A cross-sectional
      study of young people's health behaviours conducted at a music festival in
      Melbourne, Australia, in 2011. Results. 1365 young people aged 16-29 completed
      the survey; 62% were female with a mean age of 20 years. The majority (94%, n =
      1287) reported drinking alcohol during the previous 12 months; among those, 32%
      reported "binge" drinking (6+ drinks) at least weekly. Half (52%) reported ever
      using illicit drugs and 25% reported past month use. One-quarter (27%) were
      identified as being at risk of STIs through unprotected sex with new or casual
      partners during the previous 12 months. Multivariable analyses found that risky
      sexual behaviour was associated with younger age (<=19 years), younger age of
      sexual debut (<=15 years), having discussed sexual health/contraception with a
      doctor, regular binge drinking, and recent illicit drug use. Conclusion.
      Substance use correlated strongly with risky sexual behaviour. Further research
      should explore young people's knowledge of alcohol/drug-related impairment and
      associated risk-taking behaviours, and campaigns should encourage appropriate STI
      testing among music festival attendees. 

PMID- 26316975
TI  - Women and Children First: The Impact of Sexually Transmitted Infections on
      Maternal and Child Health.

PMID- 26316976
TI  - Married Men Perceptions and Barriers to Participation in the Prevention of Mother
      to-Child HIV Transmission Care in Osogbo, Nigeria.
AB  - Men's role in HIV prevention is pivotal to changing the course of the epidemic.
      Men's barriers toward participation in Prevention of Mother-to-Child Transmission
      (PMTCT) have not been adequately documented. This study is therefore designed to
      determine men's level of awareness and barriers to their participation in PMTCT
      programmes in Osogbo, Nigeria. This study was a descriptive qualitative one that
      utilized Focus Group Discussion (FGD). One-hundred and sixty married men were
      selected by convenience sampling and interviewed. Data collected were analysed
      using content analysis technique. Demographic data were analysed using SPSS 15.0
      software to generate frequency tables. Participants mean age was 31.9 +/- 5.9
      years. Many of the participants had heard about PMTCT and the majority agreed
      that it is good to accompany their wife to Antenatal Care (ANC) but only few had
      ever done so. Societal norms and cultural barriers were the leading identified
      barriers for male involvement in PMTCT programmes. The majority of the
      participant perceived it was a good idea to accompany their wife to antenatal
      care but putting this into practice was a problem due to societal norms and
      cultural barriers. Community sensitization programmes such as health education
      aimed at breaking cultural barriers should be instituted by government and
      nongovernmental agencies. 

PMID- 26316978
TI  - Prevalence and Predictors of Self-Reported Consistent Condom Usage among Male
      Clients of Female Sex Workers in Tamil Nadu, India.
AB  - Clients of female sex workers (FSWs) possess a high potential of transmitting HIV
      and other sexually transmitted infections from high risk FSWs to the general
      population. Promotion of safer sex practices among the clients is essential to
      limit the spread of HIV/AIDS epidemic. The aim of this study is to estimate the
      prevalence of consistent condom use (CCU) among clients of FSWs and to assess the
      factors associated with CCU in Tamil Nadu. 146 male respondents were recruited
      from the hotspots who reportedly had sex with FSWs in exchange for cash at least
      once in the past one month. Data were analyzed using bivariate and multivariate
      methods. Overall, 48.6 and 0.8 percent clients consistently used condoms in the
      past 12 months with FSWs and regular partners, respectively. Logistic regression
      showed that factors such as education, peers' use of condoms, and alcohol
      consumption significantly influenced clients' CCU with FSWs. Strategies for safe
      sex-behaviour are needed among clients of FSWs in order to limit the spread of
      HIV/AIDS epidemic in the general population. The role of peer-educators in
      experience sharing and awareness generation must also be emphasized. 

PMID- 26316977
TI  - Trichomonas vaginalis Incidence Associated with Hormonal Contraceptive Use and
      HIV Infection among Women in Rakai, Uganda.
AB  - Background. Data on the incidence of Trichomonas vaginalis and use of hormonal
      contraception (HC) are limited. Methods. 2,374 sexually active women aged 15-49
      years from cohort surveys in Rakai, Uganda, were included. Incidence of T.
      vaginalis was estimated per 100 person years (py) and association between HC
      (DMPA, Norplant, and oral contraceptives) and T. vaginalis infection was assessed
      by incidence rate ratios (IRR), using Poisson regression models. Results. At
      baseline, 34.9% had used HC in the last 12 months, 12.8% HIV+, 39.7% with high BV
      scores (7-10), and 3.1% syphilis positive. The 12-month incidence of T. vaginalis
      was 2.4/100 py; CI (1.90, 3.25). When stratified by type of HC used, compared to
      women who did not use HC or condoms, incidence of T. vaginalis was significantly
      higher among users of Norplant (adj.IRR = 3.01, CI: 1.07-8.49) and significantly
      lower among DMPA users (adj.IRR = 0.55, CI: 0.30, 0.98) and women who
      discontinued HC use at follow-up (adj.IRR = 0.30, CI: 0.09, 0.99). HIV infection
      was associated with an increase in incidence of T. vaginalis (adj.IRR = 2.34, CI:
      1.44, 3.78). Conclusions. Use of Norplant and being HIV+ significantly increased
      the risk of T. vaginalis, while use of DMPA and discontinuation of overall HC use
      were associated with a decreased incidence of T. vaginalis. 

PMID- 26316979
TI  - Prevalence of Trichomoniasis, Vaginal Candidiasis, Genital Herpes, Chlamydiasis,
      and Actinomycosis among Urban and Rural Women of Haryana, India.
AB  - Despite being curable reproductive tract infections (RTIs) including sexually
      transmitted infections continue to be a major health problem in developing
      countries. The present study was undertaken to know the prevalence of
      trichomoniasis, vaginal candidiasis, genital herpes, chlamydiasis, and
      actinomycosis in rural and urban women of Haryana by using wet mount, PAP smear,
      and fluorescent microscopic examination. Patients suspected of suffering from
      bacterial vaginosis were given treatment and were not included in the study. RTIs
      were seen in 16.6% of urban and 28.7% of rural women. The highest prevalence seen
      was that of trichomoniasis in both rural (24.2%) and urban (15.7%) women,
      followed by candidiasis (4.2% in rural and 0.6% in urban women), genital herpes
      (0.3% in rural and 0.2% in urban women), and chlamydiasis (0.02% in rural and
      0.05% in urban women). Pelvic actinomycosis was seen in 1.4% of rural and 0.06%
      of urban women using intrauterine contraceptive devices. Mixed infection of
      Trichomonas vaginalis with Candida spp. was seen in 6.3% of rural women only. It
      is desirable to have a baseline profile of the prevalence of various agents
      causing RTIs in a particular geographic area and population which will help in
      better syndromic management of the patients. 

PMID- 26316980
TI  - Monitoring HIV Epidemic in Pregnant Women: Are the Current Measures Enough?
AB  - Introduction. Burden of HIV in pregnant women follows overall epidemic in India.
      Hence, it is imperative that prevalence calculations in this group be accurate.
      The present study was carried out to determine prevalence of HIV in pregnant
      women attending our hospital, to determine trend of HIV infection and to compare
      our results with reported prevalence. Methods. All pregnant women are routinely
      counselled for HIV testing using opt-out strategy. Year-wise positivity and trend
      were determined in these patients over a period of five years. The positivity in
      different age groups was determined. Results. 31,609 women were tested of which
      279 (0.88%) were positive. Positivity showed a declining trend over study period
      and significant quadratic trend (biphasic, P < 0.05) was observed. The positivity
      in older age group >=35 years (1.64%) was significantly more than younger age
      groups (0.76% in 15-24-year and 0.94% in 25-34-year age group) (P = 0.0052).
      Conclusion. A significant decline in HIV positivity was seen over the study
      period. Taking into account heterogeneous nature of HIV epidemic even within the
      same district, analysis at local levels especially using the prevention of parent
      to child transmission of HIV program data is critical for HIV programming and
      resource allocation. 

PMID- 26316981
TI  - Towards the Elimination of Syphilis in a Small Developing Country.
AB  - Objective. To describe the current epidemiological features of syphilis and
      congenital syphilis in Trinidad, 2009-2012. Methods. All laboratory confirmed
      syphilis cases diagnosed through a vertical program in the Ministry of Health,
      between 1/1/2009 and 31/12/2012, were identified. All relevant data were
      collected including address which was geocoded and mapped using ArcGIS 10.0
      (Esri). Both spatial techniques and standardized incidence ratios were used to
      determine hot spots. Results. The annual cumulative incidence rate for syphilis
      remains high varying from 39 per 100 000 population in 2009 to 29 per 100 000 in
      2012. We identified 3 "hot spots," in urban areas of Trinidad. Young men and
      particularly young women in childbearing age 15-35 living in urban high density
      populations were commonly infected groups. Conclusion. The incidence of syphilis
      continues to be very high in Trinidad. New initiatives will have to be formulated
      in order to attain the global initiative to eradicate syphilis by 2015. 

PMID- 26316982
TI  - External Quality Assessment for the Detection of Chlamydia trachomatis in Urine
      Using Molecular Techniques in Belgium.
AB  - Chlamydia trachomatis is a major cause of sexually transmitted bacterial disease
      worldwide. C. trachomatis is an intracellular bacterium and its growth in vitro
      requires cell culture facilities. The diagnosis is based on antigen detection and
      more recently on molecular nucleic acid amplification techniques (NAAT) that are
      considered fast, sensitive, and specific. In Belgium, External Quality Assessment
      (EQA) for the detection of C. trachomatis in urine by NAAT was introduced in
      2008. From January 2008 to June 2012, nine surveys were organized. Fifty-eight
      laboratories participated in at least one survey. The EQA panels included
      positive and negative samples. The overall accuracy was 75.4%, the overall
      specificity was 97.6%, and the overall sensitivity was 71.4%. Two major issues
      were observed: the low sensitivity (45.3%) for the detection of low concentration
      samples and the incapacity of several methods to detect the Swedish variant of C.
      trachomatis. The reassuring point was that the overall proficiency of the Belgian
      laboratories tended to improve over time. 

PMID- 26316983
TI  - Comprehensive HIV/AIDS Knowledge and Sexual Behavior among University Students in
      Ambo, Central Ethiopia: Implication to Improve Intervention.
AB  - Background. Ethiopia has one of the lowest HIV prevalence rates in East Africa,
      but there are still more than one million people estimated to be living with HIV
      in Ethiopia. This study was aimed at assessing the comprehensive HIV/AIDS
      knowledge and sexual behavior among university students. Methodology. A cross
      sectional comparative study was done with quantitative and qualitative data
      collection with a stratified sampling technique. The quantitative data were
      edited, coded, entered, and analyzed using SPSS software version 20. Result. Both
      comprehensive knowledge of HIV/AIDS transmission and prevention method were
      higher in the intervention group (75.8% and 48.5%) than comparative group (68.6%
      and 42.5%) which had a significant difference (P < 0.05). Life time sexual
      intercourse was higher in the intervention group (40.8%) as compared to the
      comparative group (34.6%). But sexual condom utilization in the past 12 months
      was higher in the intervention group (73.2%) as compared to the comparative group
      (56.9%) which had a significant difference (P < 0.05). Similarly, history of
      sexual transmitted disease report was higher in the comparative group (6.3%) as
      compared to the intervention (4.6%). Among sexual experience respondents in the
      last 12 months, 32% of them in the intervention and 35.5% of them in the
      comparative group have had multiple sexual partners. Conclusion. The intervention
      group had higher comprehensive knowledge of HIV/AIDS and condom utilization. But
      a higher percentage of students were engaged in risky sexual behavior. Therefore,
      emphasis should be given on designing different strategy to reduce risky sexual
      behavior and increase comprehensive HIV/AIDS knowledge. 

PMID- 26316985
TI  - P-Glycoprotein Altered Expression in Alzheimer's Disease: Regional Anatomic
      Variability.
AB  - We investigated the expression of P-glycoprotein (P-gp) in brain samples of
      Alzheimer disease (AD) and normative brains (NM). Superior temporal cortex
      hippocampal and brainstem samples from 15 AD and NM brains were selected from
      comparable sites. P-gp positive capillaries and beta-amyloid (Abeta) senile
      plaques (SP) were counted. Statistical analysis of the data was performed using
      nonparametric data analysis with Mann-Whitney, Kruskal-Wallis, and Spearman's
      tests. There were no significant differences in P-gp expression between superior
      temporal and hippocampus samples. However, there were significant differences in
      P-gp expression, when comparing brainstem with both hippocampal and superior
      temporal samples in both conditions (P < 0.012; P < 0.002 in NM cases and P <
      0.001; <0.001 in AD cases); the brainstem has greater P-gp expression in each
      case and condition. In addition, there was a notable inverse negative correlation
      (P < 0.01) between P-gp expression and the presence of SPs in the AD condition
      superior temporal cortex. The results of this study suggest that there were
      significant site-dependent differences in the expression of P-gp. There may be an
      increased protective role for P-gp expression against amyloid deposition in the
      brainstem and in the superior temporal cortex of AD brains. 

PMID- 26316984
TI  - Reevaluating Metabolism in Alzheimer's Disease from the Perspective of the
      Astrocyte-Neuron Lactate Shuttle Model.
AB  - The conventional view of central nervous system (CNS) metabolism is based on the
      assumption that glucose is the main fuel source for active neurons and is
      processed in an oxidative manner. However, since the early 1990s research has
      challenged the idea that the energy needs of nerve cells are met exclusively by
      glucose and oxidative metabolism. This alternative view of glucose utilization
      contends that astrocytes metabolize glucose to lactate, which is then released
      and taken up by nearby neurons and used as a fuel source, commonly known as the
      astrocyte-neuron lactate shuttle (ANLS) model. Once thought of as a waste
      metabolite, lactate has emerged as a central player in the maintenance of
      neuronal function and long-term memory. Decreased neuronal metabolism has
      traditionally been viewed as a hallmark feature of Alzheimer's disease (AD).
      However, a more complex picture of CNS metabolism is emerging that may provide
      valuable insight into the pathophysiological changes that occur during AD and
      other neurodegenerative diseases. This review will examine the ANLS model and
      present recent evidence highlighting the critical role that lactate plays in
      neuronal survival and memory. Moreover, the role of glucose and lactate
      metabolism in AD will be re-evaluated from the perspective of the ANLS. 

PMID- 26316987
TI  - Neuroprotection by Exendin-4 Is GLP-1 Receptor Specific but DA D3 Receptor
      Dependent, Causing Altered BrdU Incorporation in Subventricular Zone and
      Substantia Nigra.
AB  - Glucagon-like peptide-1 receptor (GLP-1R) activation by exendin-4 (EX-4) is
      effective in preclinical models of Parkinson's disease (PD) and appears to
      promote neurogenesis even in severely lesioned rats. In the present study, we
      determined the effects of EX-4 on cellular BrdU incorporation in the rat
      subventricular zone (SVZ) and substantia nigra (SN). We also determined the
      specificity of this effect with the GLP-1R antagonist EX-(9-39) as well as the
      potential role of dopamine (DA) D3 receptors. Rats were administered 6-OHDA and 1
      week later given EX-4 alone, with EX-(9-39) or nafadotride (D3 antagonist) and
      BrdU. Seven days later, rats were challenged with apomorphine to evaluate
      circling. Extracellular DA was measured using striatal microdialysis and
      subsequently tissue DA measured. Tyrosine hydroxylase and BrdU were verified
      using immunohistochemistry. Apomorphine circling was reversed by EX-4 in lesioned
      rats, an effect reduced by EX-4, while both EX-(9-39) and NAF attenuated this. 6
      OHDA decreased extracellular and tissue DA, both reversed by EX-4 but again
      attenuated by EX-(9-39) or NAF. Analysis of BrdU+ cells in the SVZ revealed
      increases in 6-OHDA-treated rats which were reversed by EX-4 and antagonised by
      either EX-(9-39) or NAF, while in the SN the opposite profile was seen. 

PMID- 26316986
TI  - Oxidative Stress and Its Clinical Applications in Dementia.
AB  - Dementia is a complex disorder that mostly affects the elderly and represents a
      significant and growing public health burden in the world. Alzheimer's disease
      (AD)- associated dementia and dementia with Lewy bodies (DLB) are the most common
      forms of dementia, in which oxidative stress is significantly involved. Oxidative
      stress mechanisms may have clinical applications, that is, providing information
      for potential biomarkers. Thus brain-rich peptides with an antioxidant property,
      such as CART (cocaine- and amphetamine-regulated transcript), may be promising
      new markers. This paper summarizes the progress in research regarding oxidative
      stress in dementia with a focus on potential biomarkers in the cerebrospinal
      fluid (CSF) in the main forms of dementia. Other central and peripheral
      biomarkers, especially those considered oxidative stress related, are also
      discussed. This paper aims to provide information to improve current
      understanding of the pathogenesis and progression of dementia. It also offers
      insight into the differential diagnosis of AD and DLB. 

PMID- 26316988
TI  - Increasing Membrane Cholesterol Level Increases the Amyloidogenic Peptide by
      Enhancing the Expression of Phospholipase C.
AB  - Cerebral elevation of 42-residue amyloid beta-peptide (Abeta42) triggers neuronal
      dysfunction in Alzheimer's disease (AD). Even though a number of cholesterol
      modulating agents have been shown to affect Abeta generation, the role of
      cholesterol in the pathogenesis of AD is not clear yet. Recently, we have shown
      that increased membrane cholesterol levels downregulates phosphatidylinositol 4,5
      bisphosphate (PIP2) via activation of phospholipase C (PLC). In this study, we
      tested whether membrane cholesterol levels may affect the Abeta42 production via
      changing PIP2 levels. Increasing membrane cholesterol levels decreased PIP2 and
      increased secreted Abeta42. Supplying PIP2, by using a PIP2-carrier system,
      blocked the effect of cholesterol on Abeta42. We also found that cholesterol
      increased the expressions of beta1 and beta3 PLC isoforms (PLCbeta1, PLCbeta3).
      Silencing the expression of PLCbeta1 prevented the effects of cholesterol on PIP2
      levels as well as on Abeta42 production, suggesting that increased membrane
      cholesterol levels increased secreted Abeta42 by downregulating PIP2 via
      enhancing the expression of PLCbeta1. Thus, cholesterol metabolism may be linked
      to Abeta42 levels via PLCbeta1 expression and subsequent changes in PIP2
      metabolism. 

PMID- 26316989
TI  - Outcomes of a Peer Support Program in Multiple Sclerosis in an Australian
      Community Cohort: A Prospective Study.
AB  - Background/Objectives. This pilot study evaluated the impact of a peer support
      program on improving multiple sclerosis (MS) related psychological functions
      (depression, anxiety, and stress) and enhancing quality of life. Methodology.
      Participants (n = 33) were recruited prospectively and received an 8-week group
      face-to-face peer support program. Assessments were at baseline (T1), 6 weeks
      after program (T2), and 12 months after program (T3), using validated
      questionnaires: Depression Anxiety Stress Scale (DASS), McGill Quality of Life
      (MQOL), and Brief COPE. Results. Participants' mean age was 52; the majority were
      female (64%) and married (64%). Median time since MS diagnosis was 16 years. At
      T2, participants reported improved psychological functioning (DASS "depression,"
      "anxiety," and "stress" subscales, z values -2.36, -2.22, and -2.54, moderate
      effect sizes (r) 0.29, 0.28, and 0.32, resp.) and quality of life (MQOL SIS z
      score -2.07, r = 0.26) and were less likely to use "self-blame" as a coping
      mechanism (Brief COPE z score -2.37, r = 0.29). At T3, the positive improvements
      in stress (DASS stress subscale z score -2.41, r = 0.31) and quality of life were
      maintained (MQOL SIS, z score -2.30, r = 0.29). There were no adverse effects
      reported. 

PMID- 26316990
TI  - The Effect of Lipoic Acid Therapy on Cognitive Functioning in Patients with
      Alzheimer's Disease.
AB  - Diabetes mellitus (DM) is an important risk factor for Alzheimer's disease (AD).
      Most diabetic patients have insulin resistance (IR) that is associated with
      compensatory hyperinsulinemia, one of the mechanisms suggested for increased AD
      risk in patients with DM. Alpha-lipoic acid (ALA) is a disulfide molecule with
      antioxidant properties that has positive effects on glucose metabolism and IR.
      This study evaluated the effect of ALA treatment (600 mg/day) on cognitive
      performances in AD patients with and without DM. One hundred and twenty-six
      patients with AD were divided into two groups, according to DM presence (group A)
      or absence (group B). Cognitive functions were assessed by MMSE, Alzheimer's
      Disease Assessment Scale-cognitive (ADAS-Cog), Clinician's Interview-Based
      Impression of Severity (CIBIC), Clinical Dementia Rating (CDR), and Alzheimer's
      Disease Functional and Change Scale (ADFACS). IR was assessed by HOMA index. At
      the end of the study, MMSE scores showed a significant improvement in 43%
      patients of group A (26 subjects) and 23% of group B (15 subjects), compared to
      baseline (P = .001). Also ADAS-Cog, CIBIC, and ADFACS scores showed a significant
      improvement in group A versus group B. IR was higher in group A. Our study
      suggests that ALA therapy could be effective in slowing cognitive decline in
      patients with AD and IR. 

PMID- 26316991
TI  - The MFN2 V705I Variant Is Not a Disease-Causing Mutation: A Segregation Analysis
      in a CMT2 Family.
AB  - Charcot-Marie-Tooth (CMT) disease is a clinically and genetically heterogeneous
      group of disorders affecting both motor and sensory neurons in the peripheral
      nervous system. Mutations in the MFN2 gene cause an axonal form of CMT, CMT2A.
      The V705I variant in MFN2 has been previously reported as a disease-causing
      mutation in families with CMT2. We identified an affected index patient from an
      Australian multigenerational family with the V705I variant. Segregation analysis
      showed that the V705I variant did not segregate with the disease phenotype and
      was present in control individuals with an allele frequency of 4.4%. We,
      therefore, propose that the V705I variant is a polymorphism and not a disease
      causing mutation as previously reported. 

PMID- 26316992
TI  - Sex Differences in Presynaptic Density and Neurogenesis in Middle-Aged ApoE4 and
      ApoE Knockout Mice.
AB  - Atherosclerosis and apolipoprotein E epsilon4 (APOE4) genotype are risk factors
      for Alzheimer's disease (AD) and cardiovascular disease (CVD). Sex differences
      exist in prevalence and manifestation of both diseases. We investigated sex
      differences respective to aging, focusing on cognitive parameters in apoE4 and
      apoE knockout (ko) mouse models of AD and CVD. Presynaptic density and
      neurogenesis were investigated immunohistochemically in male and female apoE4,
      apoE ko, and wild-type mice. Middle-aged female apoE4 mice showed decreased
      presynaptic density in the inner molecular layer of the dentate gyrus of the
      hippocampus. Middle-aged female apoE ko mice showed a trend towards increased
      neurogenesis in the hippocampus compared with wild-type mice. No differences in
      these parameters could be observed in middle-aged male mice. Specific harmful
      interactions between apoE4 and estrogen could be responsible for decreased
      presynaptic density in female apoE4 mice. The trend of increased neurogenesis
      found in female apoE ko mice supports previous studies suggesting that
      temporarily increased amount of synaptic contacts and/or neurogenesis is a
      compensatory mechanism for synaptic failure. To our knowledge, no other studies
      investigating presynaptic density in aging female apoE4 or apoE ko mice are
      available. Sex-specific differences between APOE genotypes could account for some
      sex differences in AD and CVD. 

PMID- 26316993
TI  - Neurodegenerative Diseases: Multifactorial Conformational Diseases and Their
      Therapeutic Interventions.
AB  - Neurodegenerative diseases are multifactorial debilitating disorders of the
      nervous system that affect approximately 30 millionindividuals worldwide.
      Neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and
      amyotrophic lateral sclerosis diseases are the consequence of misfolding and
      dysfunctional trafficking of proteins. Beside that, mitochondrial dysfunction,
      oxidative stress, and/or environmental factors strongly associated with age have
      also been implicated in causing neurodegeneration. After years of intensive
      research, considerable evidence has accumulated that demonstrates an important
      role of these factors in the etiology of common neurodegenerative diseases.
      Despite the extensive efforts that have attempted to define the molecular
      mechanisms underlying neurodegeneration, many aspects of these pathologies remain
      elusive. However, in order to explore the therapeutic interventions directed
      towards treatment of neurodegenerative diseases, neuroscientists are now fully
      exploiting the data obtained from studies of these basic mechanisms that have
      gone awry. The novelty of these mechanisms represents a challenge to the
      identification of viable drug targets and biomarkers for early diagnosis of the
      diseases. In this paper, we are reviewing various aspects associated with the
      disease and the recent trends that may have an application for the treatment of
      the neurodegenerative disorders. 

PMID- 26316994
TI  - Amyloid Beta-Protein and Neural Network Dysfunction.
AB  - Understanding the neural mechanisms underlying brain dysfunction induced by
      amyloid beta-protein (Abeta) represents one of the major challenges for
      Alzheimer's disease (AD) research. The most evident symptom of AD is a severe
      decline in cognition. Cognitive processes, as any other brain function, arise
      from the activity of specific cell assemblies of interconnected neurons that
      generate neural network dynamics based on their intrinsic and synaptic
      properties. Thus, the origin of Abeta-induced cognitive dysfunction, and possibly
      AD-related cognitive decline, must be found in specific alterations in properties
      of these cells and their consequences in neural network dynamics. The well-known
      relationship between AD and alterations in the activity of several neural
      networks is reflected in the slowing of the electroencephalographic (EEG)
      activity. Some features of the EEG slowing observed in AD, such as the diminished
      generation of different network oscillations, can be induced in vivo and in vitro
      upon Abeta application or by Abeta overproduction in transgenic models. This
      experimental approach offers the possibility to study the mechanisms involved in
      cognitive dysfunction produced by Abeta. This type of research may yield not only
      basic knowledge of neural network dysfunction associated with AD, but also novel
      options to treat this modern epidemic. 

PMID- 26316995
TI  - Cerebrospinal Fluid Biomarkers for Kii Amyotrophic Lateral Sclerosis/Parkinsonism
      Dementia Complex.
AB  - Objective. Amyotrophic lateral sclerosis/parkinsonism-dementia complex is
      classified as one of the tauopathies. Methods. The total tau, phosphorylated tau,
      and amyloid beta42 levels were assayed in cerebrospinal fluid from patients with
      Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex (n = 12),
      Alzheimer's disease (n = 9), Parkinson's disease (n = 9), amyotrophic lateral
      sclerosis (n = 11), and controls (n = 5) using specific enzyme-linked
      immunosorbent assay methods. Results. Total tau and phosphorylated tau did not
      increase and amyloid beta42 was relatively reduced in Kii amyotrophic lateral
      sclerosis/parkinsonism-dementia complex. Relatively reduced amyloid beta42 might
      discriminate Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex from
      amyotrophic lateral sclerosis and Parkinson's disease, and the ratios of
      phosphorylated-tau to amyloid beta42 could discriminate Kii amyotrophic lateral
      sclerosis/parkinsonism-dementia complex from Alzheimer's disease. Conclusions.
      Cerebrospinal fluid analysis may be useful to differentiate amyotrophic lateral
      sclerosis/parkinsonism-dementia complex from Alzheimer's disease, amyotrophic
      lateral sclerosis, and Parkinson's disease. 

PMID- 26316996
TI  - Sleep-Wake Cycle and Daytime Sleepiness in the Myotonic Dystrophies.
AB  - Myotonic dystrophy is the most common type of muscular dystrophy in adults and is
      characterized by progressive myopathy, myotonia, and multiorgan involvement. Two
      genetically distinct entities have been identified, myotonic dystrophy type 1
      (DM1 or Steinert's Disease) and myotonic dystrophy type 2 (DM2). Myotonic
      dystrophies are strongly associated with sleep dysfunction. Sleep disturbances in
      DM1 are common and include sleep-disordered breathing (SDB), periodic limb
      movements (PLMS), central hypersomnia, and REM sleep dysregulation (high REM
      density and narcoleptic-like phenotype). Interestingly, drowsiness in DM1 seems
      to be due to a central dysfunction of sleep-wake regulation more than SDB. To
      date, little is known regarding the occurrence of sleep disorders in DM2. SDB
      (obstructive and central apnoea), REM sleep without atonia, and restless legs
      syndrome have been described. Further polysomnographic, controlled studies are
      strongly needed, particularly in DM2, in order to clarify the role of sleep
      disorders in the myotonic dystrophies. 

PMID- 26316998
TI  - Obstacle Avoidance amongst Parkinson Disease Patients Is Challenged in a
      Threatening Context.
AB  - We examined whether people with Parkinson disease (PD) have difficulty
      negotiating a gait obstruction in threatening (gait path and obstacle raised
      above floor) and nonthreatening (gait path and obstacle at floor level) contexts.
      Ten PD patients were tested in both Meds OFF and Meds ON states, along with 10
      age-matched controls. Participants completed 18 gait trials, walking 4.7 m at a
      self-selected speed while attempting to cross an obstacle 0.15 m in height placed
      near the centre point of the walkway. Kinematic and kinetic parameters were
      measured, and obstacle contact errors were tallied. Results indicated that PD
      patients made more obstacle contacts than control participants in the threatening
      context. Successful crossings by PD patients in the threatening condition also
      exhibited kinematic differences, with Meds OFF PD patients making shorter
      crossing steps, with decreased initiation and crossing velocities. The findings
      from this study lend support to the theory that PD patients rely on directed
      attention to initiate and control movement, while providing indication that the
      motor improvements provided by current PD pharmacotherapy may be limited by
      contextual interference. These movement patterns may be placing PD patients at
      risk of obstacle contact and falling. 

PMID- 26316997
TI  - Death Receptors in the Selective Degeneration of Motoneurons in Amyotrophic
      Lateral Sclerosis.
AB  - While studies on death receptors have long been restricted to immune cells, the
      last decade has provided a strong body of evidence for their implication in
      neuronal death and hence neurodegenerative disorders such as amyotrophic lateral
      sclerosis (ALS). ALS is a fatal paralytic disorder that primarily affects
      motoneurons in the brain and spinal cord. A neuroinflammatory process, associated
      with astrocyte and microglial activation as well as infiltration of immune cells,
      accompanies motoneuron degeneration and supports the contribution of non-cell
      autonomous mechanisms in the disease. Hallmarks of Fas, TNFR, LT-betaR, and
      p75(NTR) signaling have been observed in both animal models and ALS patients.
      This review summarizes to date knowledge of the role of death receptors in ALS
      and the link existing between the selective loss of motoneurons and
      neuroinflammation. It further suggests how this recent evidence could be included
      in an ultimate multiapproach to treat patients. 

PMID- 26316999
TI  - Evaluative Conditioning with Facial Stimuli in Dementia Patients.
AB  - We present results of a study investigating evaluative learning in dementia
      patients with a classic evaluative conditioning paradigm. Picture pairs of three
      unfamiliar faces with liked, disliked, or neutral faces, that were rated prior to
      the presentation, were presented 10 times each to a group of dementia patients (N
      = 15) and healthy controls (N = 14) in random order. Valence ratings of all faces
      were assessed before and after presentation. In contrast to controls, dementia
      patients changed their valence ratings of unfamiliar faces according to their
      pairing with either a liked or disliked face, although they were not able to
      explicitly assign the picture pairs after the presentation. Our finding suggests
      preserved evaluative conditioning in dementia patients. However, the result has
      to be considered preliminary, as it is unclear which factors prevented the
      predicted rating changes in the expected direction in the control group. 

PMID- 26317000
TI  - Simple Repeat-Primed PCR Analysis of the Myotonic Dystrophy Type 1 Gene in a
      Clinical Diagnostics Environment.
AB  - Myotonic dystrophy type 1 is an autosomal dominant neuromuscular disorder that is
      caused by the expansion of a CTG trinucleotide repeat in the DMPK gene. The
      confirmation of a clinical diagnosis of DM-1 usually involves PCR amplification
      of the CTG repeat-containing region and subsequent sizing of the amplification
      products in order to deduce the number of CTG repeats. In the case of repeat
      hyperexpansions, Southern blotting is also used; however, the latter has largely
      been superseded by triplet repeat-primed PCR (TP-PCR), which does not yield a CTG
      repeat number but nevertheless provides a means of stratifying patients regarding
      their disease severity. We report here a combination of forward and reverse TP
      PCR primers that allows for the simple and effective scoring of both the size of
      smaller alleles and the presence or absence of expanded repeat sequences. In
      addition, the CTG repeat-containing TP-PCR forward primer can target both the DM
      1 and Huntington disease genes, thereby streamlining the work flow for
      confirmation of clinical diagnoses in a diagnostic laboratory. 

PMID- 26317001
TI  - Immunolocalization of Kisspeptin Associated with Amyloid-beta Deposits in the
      Pons of an Alzheimer's Disease Patient.
AB  - The pons region of the Alzheimer's disease (AD) brain is one of the last to show
      amyloid-beta (Abeta) deposits and has been suggested to contain neuroprotective
      compounds. Kisspeptin (KP) is a hormone that activates the hypothalamic-pituitary
      gonadal axis and has been suggested to be neuroprotective against Abeta toxicity.
      The localization of KP, plus the established endogenous neuroprotective compounds
      corticotropin releasing hormone (CRH) and catalase, in tissue sections from the
      pons region of a male AD subject has been determined in relation to Abeta
      deposits. Results showed Abeta deposits also stained with KP, CRH, and catalase
      antibodies. At high magnification the staining of deposits was either KP or
      catalase positive, and there was only a limited area of the deposits with KP
      catalase colocalization. The CRH does not bind Abeta, whilst both KP and catalase
      can bind Abeta, suggesting that colocalization in Abeta deposits is not
      restricted to compounds that directly bind Abeta. The neuroprotective actions of
      KP, CRH, and catalase were confirmed in vitro, and fibrillar Abeta preparations
      were shown to stimulate the release of KP in vitro. In conclusion,
      neuroprotective KP, CRH, and catalase all colocalize with Abeta plaque-like
      deposits in the pons region from a male AD subject. 

PMID- 26317002
TI  - Clinical and Genetic Study of Algerian Patients with Spinal Muscular Atrophy.
AB  - Spinal muscular atrophy (SMA) is the second most common lethal autosomal
      recessive disorder. It is divided into the acute Werdnig-Hoffmann disease (type
      I), the intermediate form (type II), the Kugelberg-Welander disease (type III),
      and the adult form (type IV). The gene involved in all four forms of SMA, the so
      called survival motor neuron (SMN) gene, is duplicated, with a telomeric (tel SMN
      or SMN1) and a centromeric copy (cent SMN or SMN2). SMN1 is homozygously deleted
      in over 95% of SMA patients. Another candidate gene in SMA is the neuronal
      apoptosis inhibitory protein (NAIP) gene; it shows homozygous deletions in 45-67%
      of type I and 20-42% of type II/type III patients. Here we studied the SMN and
      NAIP genes in 92 Algerian SMA patients (20 type I, 16 type II, 53 type III, and 3
      type IV) from 57 unrelated families, using a semiquantitative PCR approach.
      Homozygous deletions of SMN1 exons 7 and/or 8 were found in 75% of the families.
      Deletions of exon 4 and/or 5 of the NAIP gene were found in around 25%.
      Conversely, the quantitative analysis of SMN2 copies showed a significant
      correlation between SMN2 copy number and the type of SMA. 

PMID- 26317003
TI  - Bacopa monnieri Phytochemicals Mediated Synthesis of Platinum Nanoparticles and
      Its Neurorescue Effect on 1-Methyl 4-Phenyl 1,2,3,6 Tetrahydropyridine-Induced
      Experimental Parkinsonism in Zebrafish.
AB  - Current discovery demonstrates the rapid formation of platinum nanoparticles
      using leaf extract of a neurobeneficial plant, Bacopa monnieri (BmE). The
      nanoparticles (BmE-PtNPs) were stabilized and then coated with varied
      phytochemicals present within the leaf extract. These nanoparticles demonstrated
      the same activity of Complex I, as that of oxidizing NADH to NAD(+) using a
      spectrophotometric method. This suggests that BmE-PtNPs are a potential medicinal
      substance for oxidative stress mediated disease with suppressed mitochondrial
      complex I, namely, Parkinson's disease (PD). Hence, the neuroprotective
      potentials of the phytochemical coated nanoparticle were explored in 1-methyl 4
      phenyl 1,2,3,6 tetrahydropyridine- (MPTP-)induced experimental Parkinsonism in
      zebrafish model. BmE-PtNPs pretreatment significantly reversed toxic effects of
      MPTP by increasing the levels of dopamine, its metabolites, GSH and activities of
      GPx, catalase, SOD and complex I, and reducing levels of MDA along with enhanced
      locomotor activity. Taken together, these findings suggest that BmE-PtNPs have
      protective effect in MPTP-induced neurotoxicity in this model of Parkinson's
      disease via their dual functions as mitochondrial complex I and antioxidant
      activity. 

PMID- 26317004
TI  - Prevalence and Cognitive Bases of Subjective Memory Complaints in Older Adults:
      Evidence from a Community Sample.
AB  - Objectives. To estimate the prevalence of subjective memory complaints (SMCs) in
      a sample of community-dwelling, older adults and to examine cognitive bases of
      these complaints. Participants. 499 community-dwelling adults, 65 and older.
      Measurements. A telephone survey consisting of cognitive tests and clinical and
      sociodemographic variables. SMCs were based on subjects' evaluations and
      subjects' perceptions of others' evaluations. Analysis. Logistic regression was
      used to model the risk for SMCs as a function of the cognitive, clinical, and
      sociodemographic variables. We tested for interactions of the cognitive variables
      with age, education, and gender. Results. 27.1% reported memory complaints. Among
      the younger age, better objective memory performance predicted lower risk for
      SMCs, while among the older age, better memory had no effect on risk. Among the
      better-educated people, better global cognitive functioning predicted lower risk
      for SMCs, while among the less-educated people, better global cognitive
      functioning had no effect on SMC risk. When predicting others' perceptions,
      better objective memory was associated with lower risk for SMCs. Conclusion.
      Objective memory performance and global cognitive functioning are associated with
      lower risk for SMCs, but these relationships are the strongest for the younger
      age and those with more education, respectively. Age and education may affect the
      ability to accurately appraise cognitive functioning. 

PMID- 26317005
TI  - Comment on "Prevalence and Cognitive Bases of Subjective Memory Complaints in
      Older Adults: Evidence from a Community Sample".

PMID- 26317006
TI  - Essential Tremor in the Elderly and Risk for Dementia.
AB  - The objective is to examine the risk of dementia in subjects with essential
      tremor (ET) involved in the Arizona Study of Aging and Neurodegenerative
      Disorders. All subjects were free of a neurodegenerative diagnosis at baseline
      and had annual motor, general neurological, and neuropsychological assessments.
      Subjects with ET were compared with controls for the risk of dementia. There were
      83 subjects with ET and 424 subjects without tremor. Mean age at study entry was
      80 +/- 5.9 for ET and 76 +/- 8.5 for controls. Median tremor duration was 5.2
      years at study entry. Followup was a median of 5.4 years (range 0.9 to 12.1). The
      hazard ratio for the association between ET and dementia was 0.79 (95% CI 0.33 to
      1.85). The hazard ratio for the association between tremor onset at age 65 or
      over, versus onset before age 65, was 2.1 (95% CI 0.24 to 18) and the hazard
      ratio for the association between tremor duration greater than 5 years, versus
      less than 5 years, was 0.46 (95% CI 0.08 to 2.6). We conclude that all elderly ET
      was not associated with an increased risk of dementia but that a subset of
      subjects with older age onset/shorter duration tremor may be at higher risk. 

PMID- 26317007
TI  - Nicotine-Cadmium Interaction Alters Exploratory Motor Function and Increased
      Anxiety in Adult Male Mice.
AB  - In this study we evaluated the time dependence in cadmium-nicotine interaction
      and its effect on motor function, anxiety linked behavioural changes, serum
      electrolytes, and weight after acute and chronic treatment in adult male mice.
      Animals were separated randomly into four groups of n = 6 animals each. Treatment
      was done with nicotine, cadmium, or nicotine-cadmium for 21 days. A fourth group
      received normal saline for the same duration (control). Average weight was
      determined at 7-day interval for the acute (D1-D7) and chronic (D7-D21) treatment
      phases. Similarly, the behavioural tests for exploratory motor function (open
      field test) and anxiety were evaluated. Serum electrolytes were measured after
      the chronic phase. Nicotine, cadmium, and nicotine-cadmium treatments caused no
      significant change in body weight after the acute phase while cadmium-nicotine
      and cadmium caused a decline in weight after the chronic phase. This suggests the
      role of cadmium in the weight loss observed in tobacco smoke users. Both nicotine
      and cadmium raised serum Ca(2+) concentration and had no significant effect on
      K(+) ion when compared with the control. In addition, nicotine-cadmium treatment
      increased bioaccumulation of Cd(2+) in the serum which corresponded to a decrease
      in body weight, motor function, and an increase in anxiety. 

PMID- 26317008
TI  - Glial Cell Line-Derived Neurotrophic Factor Family Members Reduce Microglial
      Activation via Inhibiting p38MAPKs-Mediated Inflammatory Responses.
AB  - Previous studies have shown that glial cell line-derived neurotrophic factor
      (GDNF) family ligands (GFL) are potent survival factors for dopaminergic neurons
      and motoneurons with therapeutic potential for Parkinson's disease. However,
      little is known about direct influences of the GFL on microglia function, which
      are known to express part of the GDNF receptor system. Using RT-PCR and
      immunohistochemistrym we investigated the expression of the GDNF family receptor
      alpha 1 (GFR alpha) and the coreceptor transmembrane receptor tyrosine kinase
      (RET) in rat microglia in vitro as well as the effect of GFL on the expression of
      proinflammatory molecules in LPS activated microglia. We could show that GFL are
      able to regulate microglia functions and suggest that part of the well known
      neuroprotective action may be related to the suppression of microglial
      activation. We further elucidated the functional significance and
      pathophysiological implications of these findings and demonstrate that microglia
      are target cells of members of the GFL (GDNF and the structurally related
      neurotrophic factors neurturin (NRTN), artemin (ARTN), and persephin (PSPN)). 

PMID- 26317009
TI  - Multidisciplinary Interventions in Motor Neuron Disease.
AB  - Motor neuron disease is a neurodegenerative disease characterized by loss of
      upper motor neuron in the motor cortex and lower motor neurons in the brain stem
      and spinal cord. Death occurs 2-4 years after the onset of the disease. A complex
      interplay of cellular processes such as mitochondrial dysfunction, oxidative
      stress, excitotoxicity, and impaired axonal transport are proposed pathogenetic
      processes underlying neuronal cell loss. Currently evidence exists for the use of
      riluzole as a disease modifying drug; multidisciplinary team care approach to
      patient management; noninvasive ventilation for respiratory management; botulinum
      toxin B for sialorrhoea treatment; palliative care throughout the course of the
      disease; and Modafinil use for fatigue treatment. Further research is needed in
      management of dysphagia, bronchial secretion, pseudobulbar affect, spasticity,
      cramps, insomnia, cognitive impairment, and communication in motor neuron
      disease. 

PMID- 26317010
TI  - Differential Changes in Postsynaptic Density Proteins in Postmortem Huntington's
      Disease and Parkinson's Disease Human Brains.
AB  - NMDA and AMPA-type glutamate receptors and their bound membrane-associated
      guanylate kinases (MAGUKs) are critical for synapse development and plasticity.
      We hypothesised that these proteins may play a role in the changes in synapse
      function that occur in Huntington's disease (HD) and Parkinson's disease (PD). We
      performed immunohistochemical analysis of human postmortem brain tissue to
      examine changes in the expression of SAP97, PSD-95, GluA2 and GluN1 in human
      control, and HD- and PD-affected hippocampus and striatum. Significant increases
      in SAP97 and PSD-95 were observed in the HD and PD hippocampus, and PSD95 was
      downregulated in HD striatum. We observed a significant increase in GluN1 in the
      HD hippocampus and a decrease in GluA2 in HD and PD striatum. Parallel
      immunohistochemistry experiments in the YAC128 mouse model of HD showed no change
      in the expression levels of these synaptic proteins. Our human data show that
      major but different changes occur in glutamatergic proteins in HD versus PD human
      brains. Moreover, the changes in human HD brains differ from those occurring in
      the YAC128 HD mouse model, suggesting that unique changes occur at a subcellular
      level in the HD human hippocampus. 

PMID- 26317011
TI  - Valproic Acid Neuroprotection in the 6-OHDA Model of Parkinson's Disease Is
      Possibly Related to Its Anti-Inflammatory and HDAC Inhibitory Properties.
AB  - Parkinson's disease is a neurodegenerative disorder where the main hallmark is
      the dopaminergic neuronal loss. Besides motor symptoms, PD also causes cognitive
      decline. Although current therapies focus on the restoration of dopamine levels
      in the striatum, prevention or disease-modifying therapies are urgently needed.
      Valproic acid (VA) is a wide spectrum antiepileptic drug, exerting many
      biochemical and physiological effects. It has been shown to inhibit histone
      deacetylase which seems to be associated with the drug neuroprotective action.
      The objectives were to study the neuroprotective properties of VA in a model of
      Parkinson's disease, consisting in the unilateral striatal injection of the
      neurotoxin 6-OHDA. For that, male Wistar rats (250 g) were divided into the
      groups: sham-operated (SO), untreated 6-OHDA-lesioned, and 6-OHDA-lesioned
      treated with VA (25 or 50 mg/kg). Oral treatments started 24 h after the
      stereotaxic surgery and continued daily for 2 weeks, when the animals were
      subjected to behavioral evaluations (apomorphine-induced rotations and open-field
      tests). Then, they were sacrificed and had their mesencephalon, striatum, and
      hippocampus dissected for neurochemical (DA and DOPAC determinations),
      histological (Fluoro-Jade staining), and immunohistochemistry evaluations (TH, OX
      42, GFAP, TNF-alpha, and HDAC). The results showed that VA partly reversed
      behavioral and neurochemical alterations observed in the untreated 6-OHDA
      lesioned rats. Besides, VA also decreased neuron degeneration in the striatum and
      reversed the TH depletion observed in the mesencephalon of the untreated 6-OHDA
      groups. This neurotoxin increased the OX-42 and GFAP immunoreactivities in the
      mesencephalon, indicating increased microglia and astrocyte reactivities,
      respectively, which were reversed by VA. In addition, the immunostainings for TNF
      alpha and HDAC demonstrated in the untreated 6-OHDA-lesioned rats were also
      decreased after VA treatments. These results were observed not only in the CA1
      and CA3 subfields of the hippocampus, but also in the temporal cortex. In
      conclusion, we showed that VA partly reversed the behavioral, neurochemical,
      histological, and immunohistochemical alterations observed in the untreated 6
      OHDA-lesioned animals. These effects are probably related to the drug anti
      inflammatory activity and strongly suggest that VA is a potential candidate to be
      included in translational studies for the treatment of neurodegenerative diseases
      as PD. 

PMID- 26317012
TI  - Prostasin: An Epithelial Sodium Channel Regulator.
AB  - Prostasin is a glycophosphatidylinositol-anchored protein which is found in
      prostate gland, kidney, bronchi, colon, liver, lung, pancreas, and salivary
      glands. It is a serine protease with trypsin-like substrate specificity which was
      first purified from seminal fluid in 1994. In the last decade, its diverse roles
      in various biological and physiological processes have been elucidated. Many
      studies done to date suggest that prostasin is one of several membrane peptidases
      regulating epithelial sodium channels in mammals. A comprehensive literature
      search was conducted from the websites of Pubmed Central, the US National Library
      of Medicine's digital archive of life sciences literature and the National
      Library of Medicine. The data was also assessed from journals and books that
      published relevant articles in this field. Understanding the mechanism by which
      prostasin and its inhibitors regulate sodium channels has provided a new insight
      into the treatment of hypertension and some other diseases like cystic fibrosis.
      Prostasin plays an important role in epidermal growth factor receptor (EGFR)
      signal modulation. Extracellular proteases have been implicated in tumor
      metastasis and local tissue invasion because of their ability to degrade
      extracellular matrices.

PMID- 26317013
TI  - Neopterin in Diagnosis and Monitoring of Infectious Diseases.
AB  - Neopterin is produced by activated monocytes, macrophages, and dendritic cells
      upon stimulation by interferon gamma produced by T-lymphocytes. Quantification of
      neopterin in body fluids has been achieved by standard high-performance liquid
      chromatography, radioimmunoassays, and enzyme-linked immunosorbent assays.
      Neopterin levels predict HIV-related mortality more efficiently than clinical
      manifestations. Successful highly active antiretroviral therapy is associated
      with a decrease in neopterin levels. Elevated neopterin levels were associated
      with hepatitis by hepatitis A, B, and C viruses. Serum neopterin levels were
      found to be a predictor of response to treatment of chronic HCV infection with
      pegylated interferon combined with ribavirin. Neopterin levels of patients with
      pulmonary tuberculosis were found to be higher in patients with more extensive
      radiological changes. Elimination of blood donors with elevated neopterin levels
      to reduce risk of transmission of infections with known and unknown viral
      pathogens has been undertaken. Neopterin measurement is hereby more cost
      effective but less sensitive than screening using polymerase chain reaction based
      assays. In conclusion neopterin is a nonspecific marker of activated T-helper
      cell 1 dominated immune response. It may be a useful marker for monitoring of
      infectious disease activity during treatment and for more accurate estimation of
      extent of disease and prognosis. 

PMID- 26317015
TI  - eNOS Gene Variant in Patients with Coronary Artery Disease.
AB  - Subject & Aim. Endothelial nitric oxide synthase (eNOS) is one of the most
      important candidate genes in CAD. A functional polymorphism within eNOS gene is a
      27 bp VNTR on its intron 4 which has been shown to be associated with various
      diseases. In this study we investigated eNOS VNTR polymorphism in addition to
      eNOS gene expression profile in patients with CAD. Material and Methods. The
      study comprised patients with angiographically confirmed CAD (CAD(+)) and
      individuals with normal coronary as CAD(-). eNOS VNTR polymorphism frequencies
      were determined in both groups. In addition eNOS gene expression profile was
      examined using a quantitative real-time PCR. Results. We have found that aa
      genotype was significantly increasing the risk of CAD in our patients (aa versus
      ab + bb, P = 0.02, OR = 3.5; 95% CI: = 0.98 to 16.2). The differences in eNOS
      expression were not significant between patients and normal group; however in
      CAD(+) patients eNOS expression was higher than the expression level of patients
      carrying other genotypes (P = 0.16). Conclusion. We have observed that eNOS gene
      polymorphism was associated with CAD in angiography-confirmed patients. However,
      the difference in eNOS gene expression was not statistically significant between
      patients and control which might be due to the contribution of other confounding
      factors which require further investigations. 

PMID- 26317014
TI  - Markers of Oxidative Stress during Diabetes Mellitus.
AB  - The prevalence of diabetes mellitus is rising all over the world. Uncontrolled
      state of hyperglycemia due to defects in insulin secretion/action leads to a
      variety of complications including peripheral vascular diseases, nephropathy,
      neuropathy, retinopathy, morbidity, and/or mortality. Large body of evidence
      suggests major role of reactive oxygen species/oxidative stress in development
      and progression of diabetic complications. In the present paper, we have
      discussed the recent researches on the biomarkers of oxidative stress during type
      2 diabetes mellitus. 

PMID- 26317016
TI  - Urinary Measurement of Neutrophil Gelatinase Associated Lipocalin and Kidney
      Injury Molecule-1 Helps Diagnose Acute Pyelonephritis in a Preclinical Model.
AB  - Background. The study assessed whether measurement of urinary biomarkers of acute
      kidney injury could be helpful in diagnosing acute pyelonephritis and subsequent
      scarring. Method. Escherichia coli J96 (0.3 mL inoculum containing 1 * 10(9)/mL)
      was directly injected into the renal cortex of 3-week-old female Sprague Dawley
      rats (n = 20), with saline substituted in a control group (n = 10). Following the
      injection, urine was collected 2, 7, 14, 28, and 42 days after injection. Urinary
      neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule-1 (Kim
      1), and interleukin-18 were quantitatively measured using enzyme-linked
      immunosorbent assay (ELISA). The levels of the biomarkers were adjusted for
      creatinine. Time course changes within a group or between the groups were
      compared. Correlation analysis was performed to understand the relationship
      between urinary levels and histological scarring. Results. Significantly elevated
      urinary NGAL was evident at two and seven days after injection, and Kim-1 was
      elevated at two days after injection. Receiver operating characteristic analyses
      confirmed the sensitivity of these markers at these times. No urinary marker at
      acute stage of APN was correlated with the amount of future scarring, negating
      their predictive value. Conclusion. Urinary NGAL and Kim-1 could be helpful in
      diagnosing febrile urinary tract infection in children. 

PMID- 26317017
TI  - Glucose-6-Phosphate Dehydrogenase Activity and Protein Oxidative Modification in
      Patients with Type 2 Diabetes Mellitus.
AB  - Objectives. The aim of the present investigation was to study the activity of
      glucose-6-phosphate dehydrogenase (G6PD) and correlate its activity to protein
      oxidation markers in type 2 diabetic patients under poor glycemic control.
      Methods. G6PD activity, protein carbonyl group concentration, and total thiol
      group content were measured in blood samples of 40 patients with type 2 diabetes
      mellitus under poor glycemic control and 20 healthy control subjects. Results.
      G6PD activity and total thiol group content decreased significantly while
      glycated hemoglobin (HbA1C) and protein carbonyl group concentration increased
      significantly in diabetic patients than in the controls (P < 0.001). In addition,
      Obtained results revealed that, in diabetics, G6PD activity negatively correlated
      to protein carbonyl and HbA1C (r = -0.77 and -0.65, resp.), while positively
      correlated to total thiol (r = 0.66) and protein carbonyl negatively correlated
      to total thiol (r = -0.85), while positively correlated to HbA1C (r = 0.43). Also
      in controls, G6PD activity negatively correlated to protein carbonyl and HbA1C (r
      = -0.57 and -0.56, resp.), while positively correlated to total thiol (r = 0.5)
      and protein carbonyl negatively correlated to total thiol (r = -0.48), while
      positively correlated to HbA1C (r = 0.68). Conclusions. We concluded that G6PD
      activity decreased in diabetics than in controls and was negatively correlated to
      oxidative stress markers and HbA1C. G6PD activity can be taken as a biomarker of
      oxidative stress and poor glycemic control in type 2 diabetic patients. 

PMID- 26317019
TI  - Tissue Reactivity of the 14F7 Mab Raised against N-Glycolyl GM3 Ganglioside in
      Tumors of Neuroectodermal, Mesodermal, and Epithelial Origin.
AB  - The expression of N-glycolylneuraminic acid forming the structure of gangliosides
      and/or other glycoconjugates (Hanganutziu-Deicher antigen) in human has been
      considered as a tumor-associated antigen. Specifically, some reports of 14F7 Mab
      (a highly specific Mab raised against N-glycolyl GM3 ganglioside) reactivity in
      human tumors have been recently published. Nevertheless, tumors of epithelial
      origin have been mostly evaluated. The goal of the present paper was to evaluate
      the immunohistochemical recognition of 14F7 Mab in different human tumors of
      neuroectodermal, mesodermal, and epithelial origins using an immunoperoxidase
      staining method. Samples of fetal, normal, and reactive astrocytosis of the brain
      were also included in the study. In general, nontumoral tissues, as well as, low
      grade brain tumors showed no or a limited immunoreaction with 14F7 Mab.
      Nevertheless, high-grade astrocytomas (III-IV) and neuroblastomas, as well as,
      sarcomas and thyroid carcinomas were mostly reactive with 14F7. No reaction was
      evidenced in medulloblastomas and ependymoblastomas. Our data suggest that the
      expression of N-glycolyl GM3 ganglioside could be related to the aggressive
      behavior of malignant cells, without depending on the tumor origin. Our data
      could also support the possible use of N-glycolyl GM3 as a target for both active
      and passive immunotherapies of malignancies expressing this molecule. 

PMID- 26317020
TI  - Immunohistochemical Characterization of Three Monoclonal Antibodies Raised
      against the Epidermal Growth Factor and Its Receptor in Non-Small-Cell Lung
      Cancer: Their Potential Use in the Selection of Patients for Immunotherapy.
AB  - Adequate methods to identify which lung cancer patients are most likely to
      benefit from the targeted drugs against both epidermal growth factor
      receptor/epidermal growth factor (EGFR/EGF) are needed. For this reason, we
      evaluated both the tissue reactivity of ior egf/r3 monoclonal antibody (Mab) in
      human lung carcinomas and its biological activity in NCI-H125 cells.
      Additionally, we assessed the tissue expression of EGF using two Mabs, CB-EGF1
      and CB-EGF2. The overexpression of EGFR was detected in 33.33% and 62.71% of
      small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC),
      respectively. The ability of ior egf/r3 Mab to bind the extracellular domain of
      EGFR inhibiting cell proliferation and inducing apoptosis in NCI-H125 cells was
      also demonstrated. The EGF expression was observed in about 17% and 70% of SCLC
      and NSCLC, respectively. However, differences in the reactivity of CB-EGF1 and CB
      EGF2 were evidenced. A dual expression of EGFR and EGF was observed in 16.67% and
      57.63% of SCLC and NSCLC patients, respectively. But, a correlation between them
      was only obtained in NSCLC. Our results permit to recommend the development of
      diagnostic kits using ior egf/r3 and/or CB-EGF1 Mabs in order to achieve a better
      selection of patients to EGFR/EGF-targeting treatment. 

PMID- 26317018
TI  - Amyotrophic Lateral Sclerosis and Metabolomics: Clinical Implication and
      Therapeutic Approach.
AB  - Amyotrophic lateral sclerosis (ALS) is one of the most common motor
      neurodegenerative disorders, primarily affecting upper and lower motor neurons in
      the brain, brainstem, and spinal cord, resulting in paralysis due to muscle
      weakness and atrophy. The majority of patients die within 3-5 years of symptom
      onset as a consequence of respiratory failure. Due to relatively fast progression
      of the disease, early diagnosis is essential. Metabolomics offer a unique
      opportunity to understand the spatiotemporal metabolic crosstalks through the
      assessment of body fluids and tissue. So far, one of the most challenging issues
      related to ALS is to understand the variation of metabolites in body fluids and
      CNS with the progression of disease. In this paper we will review the changes in
      metabolic profile in response to disease progression condition and also see the
      therapeutic implication of various drugs in ALS patients. 

PMID- 26317022
TI  - Association between a Tetranucleotide Repeat Polymorphism of SPAG16 Gene and
      Cataract in Male Children.
AB  - Purpose. Studies involving genotyping of STR markers at 2q34 have repeatedly
      found the region to host the disease haplotype for pediatric cataract. Present
      study investigated the association of D2S2944 marker, in sperm associated antigen
      16 (SPAG16) gene and rs2289917 polymorphism, in gamma-crystallin B gene, with
      childhood cataract. Methods. 97 pediatric cataract cases and 110 children with no
      ocular defects were examined for tetranucleotide repeat marker/SNP using PCR
      SSLP/RFLP techniques. Polymorphisms were assessed for association using
      contingency tables and linkage disequilibrium among alleles of the markers was
      estimated. Energy-optimization program predicted the secondary structure models
      of repeats of D2S2944. Results. Seven alleles of D2S2944, with 9-15 "GATA"
      repeats, were observed. Frequency of the longer allele of D2S2944, >=(GATA)13
      repeats, was 0.73 in cases and 0.56 in controls (P = 0.0123). Male children
      bearing >=(GATA)13 repeats showed >3-fold higher risk for cataract (CI95% = 1.43
      7.00, P = 0.0043, P c = 0.0086) as compared to female children (OR = 1.19, CI95%
      = 0.49-2.92, P = 0.70). Cases with haplotype->=(GATA)13 of D2S2944 and "C" allele
      rs2289917-have a higher risk for pediatric cataract (OR = 2.952, CI95% =
      1.595~5.463, P = 0.000453). >(GATA)13 repeats formed energetically more favorable
      stem-loop structure. Conclusion. Intragenic microsatellite repeat expansion in
      SPAG16 gene increases predisposition to pediatric cataract by probably
      interfering posttranscriptional events and affecting the expression of adjacent
      lens transparency gene/s in a gender bias manner. 

PMID- 26317021
TI  - Censored Data Analysis Reveals Effects of Age and Hepatitis C Infection on C
      Reactive Protein Levels in Healthy Adult Chimpanzees (Pan troglodytes).
AB  - C-reactive protein, a conserved acute-phase protein synthesized in the liver and
      involved in inflammation, infection, and tissue damage, is an informative
      biomarker for human cardiovascular disease. Out of 258 captive adult common
      chimpanzees (Pan troglodytes) assayed for CRP, 27.9% of the data were below the
      quantitation limit. Data were analyzed by the Kaplan-Meier method and results
      compared to other methods for handling censored data (including deletion,
      replacement, and imputation). Kaplan-Meier results demonstrated a modest age
      effect and a strong effect of HCV infection in reducing CRP but did not allow
      inference of reference intervals. Results of other methods varied considerably.
      Substitution schemes differed widely in statistical significance, with estimated
      group means biased by the size of the substitution constant, while inference of
      unbiased reference intervals was impossible. Single imputation gave reasonable
      statistical inferences but unreliable reference intervals. Multiple imputation
      gave reliable results, for both statistical inference and reference intervals,
      and was comparable to the Kaplan-Meier standard. Other methods should be avoided.
      CRP did not predict cardiovascular disease, but CRP levels were reduced by 50% in
      animals with hepatitis C infection and showed inverse relationships with 2 liver
      function enzymes. Results suggested that hsCRP can be an informative biomarker of
      chronic hepatic dysfunction. 

PMID- 26317023
TI  - T-Cell Response to Hepatitis B Core Antigen: Identification of Prior Exposure to
      and Confirmatory Testing for Screening for Anti-HBc.
AB  - Background. During routine donor screening in the blood bank, it is not uncommon
      to find isolated reactivity for anti-HBc in the absence of detectable HBV DNA in
      a first donation but absence of reactivity to anti-HBc in subsequent donations,
      suggesting a false-positive result for anti-HBc. Study Design and Methods. The
      blood donor population was screened between January 2010 and October 2011. We
      selected 2,126 donations positive only for anti-HBc from a total of 125,068
      donations. During the process, OBI donors were identified, and their HBcAg
      specific T-cell response was analyzed and compared to donors with chronic (HBsAg
      positive) and recovered (anti-HBc only) infection. We analyzed correlations
      between signal levels (Co/s) in the competitive assay for anti-HBc and HBV DNA
      detection. Results. In the 21-month study period, 21 blood donors with anti-HBc
      alone were identified as OBI (1 in each 5955 donors). The relevant finding was
      the observation that anti-HBc only subjects with Co/s >= 0.1 did not have either
      HBcAg-specific T-cells or detectable HBV DNA and OBI subjects presented with Co/s
      <= 0.1 and HBcAg T-cell response. In the subset of 21 OBI subjects, 9 donors
      remained positive for HBcAg T-cell response after four collections. In all 9
      samples, we observed HBV DNA fluctuation. Conclusion. Our data suggest that HBcAg
      specific T-cell response could be used to confirm anti-HBc serological status,
      distinguishing previous exposure to Hepatitis B virus from anti-HBc false
      positive results. 

PMID- 26317024
TI  - Population-Sequencing as a Biomarker for Sample Characterization.
AB  - Sequencing is accepted as the "gold" standard for genetic analysis and continues
      to be used as a validation and reference tool. The idea of using sequence
      analysis directly for sample characterization has been met with skepticism.
      However, herein, utility of direct use of sequencing to identify multiple genomes
      present in samples is presented and reviewed. All samples and "pure" isolates are
      populations of genomes. Population-Sequencing is the use of probabilistic
      matching tools in combination with large volumes of sequence information to
      identify genomes present, based on DNA analysis across entire genomes to
      determine genome assignments, to calculate confidence scores of major and minor
      genome content. Accurate genome identification from mixtures without culture
      purification steps can achieve phylogenetic classification by direct analysis of
      millions of DNA fragments. Genome sequencing data of mixtures can function as
      biomarkers for use to interrogate genetic content of samples and to establish a
      sample profile, inclusive of major and minor genome components, drill down to
      identify rare SNP and mutation events, compare relatedness of genetic content
      between samples, profile-to-profile, and provide a probabilistic or statistical
      scoring confidence for sample characterization and attribution. The application
      of Population-Sequencing will facilitate sample characterization and genome
      identification strategies. 

PMID- 26317025
TI  - Effect of Quercetin on Haematobiochemical and Histological Changes in the Liver
      of Polychlorined Biphenyls-Induced Adult Male Wistar Rats.
AB  - Polychlorinated biphenyls exposure damages the rat liver cells. Hematological
      parameters such as hemoglobin, packed cell volume, red-blood cells, white-blood
      cells, neutrophils, platelet counts, and RBC indices were significantly
      decreased. Polymorphs, eosinophil counts, and erythrocyte sedimentation rate were
      significantly increased. Serum liver enzymes such as aspartate transaminase,
      alanine transaminase, alkaline phosphatase, and gamma-glutamyl transferase were
      increased by PCBs treatment. Serum lipid profiles such as cholesterol,
      triglycerides, low-density lipoproteins and very-low-density lipoproteins were
      increased in PCBs-treated rats. High-density lipoprotein, total protein, albumin,
      globulin levels, and albumin/globulin ratio were also decreased after PCB
      exposure. Then levels of sodium, potassium, chloride, and bicarbonate were also
      altered. Serum glucose levels were increased along with total bilirubin after
      PCBs exposure. Simultaneous quercetin supplementation significantly protected the
      PCBs-induced changes of hematobiochemical parameters. Thus, quercetin shows a
      protective role against PCBs-induced alterations in the hematological and
      biochemical parameters. 

PMID- 26317026
TI  - Immunoreactivity of Pluripotent Markers SSEA-5 and L1CAM in Human Tumors,
      Teratomas, and Induced Pluripotent Stem Cells.
AB  - Pluripotent stem cell markers can be useful for diagnostic evaluation of human
      tumors. The novel pluripotent marker stage-specific embryonic antigen-5 (SSEA-5)
      is expressed in undifferentiated human induced pluripotent cells (iPSCs), but
      little is known about SSEA-5 expression in other primitive tissues (e.g., human
      tumors). We evaluated SSEA-5 immunoreactivity patterns in human tumors, cell
      lines, teratomas, and iPS cells together with another pluripotent cell surface
      marker L1 cell adhesion molecule (L1CAM). We tested two hypotheses: (1) SSEA-5
      and L1CAM would be immunoreactive and colocalized in human tumors; (2) SSEA-5 and
      L1CAM immunoreactivity would persist in iPSCs following retinal differentiating
      treatment. SSEA-5 immunofluorescence was most pronounced in primitive tumors,
      such as embryonal carcinoma. In tumor cell lines, SSEA-5 was highly
      immunoreactive in Capan-1 cells, while L1CAM was highly immunoreactive in U87MG
      cells. SSEA-5 and L1CAM showed colocalization in undifferentiated iPSCs, with
      immunopositive iPSCs remaining after 20 days of retinal differentiating
      treatment. This is the first demonstration of SSEA-5 immunoreactivity in human
      tumors and the first indication of SSEA-5 and L1CAM colocalization. SSEA-5 and
      L1CAM warrant further investigation as potentially useful tumor markers for
      histological evaluation or as markers to monitor the presence of undifferentiated
      cells in iPSC populations prior to therapeutic use. 

PMID- 26317027
TI  - Relationships between Plasma Micronutrients, Serum IgE, and Skin Test Reactivity
      and Asthma among School Children in Rural Southwest Nigeria.
AB  - Objective. Increasing prevalence of asthma has been attributed to changes in
      lifestyle and environmental exposures. We conducted a case-control study to
      investigate the relationship between serum micronutrients and asthma in rural
      school children in Nigeria. Methods. We administered questionnaires to 1,562
      children to identify children with asthma. Serum concentration levels of 12
      micronutrients were determined in asthma cases (N = 37) and controls (N = 30).
      Allergy skin prick test and spirometry were also performed. Results. Plasma
      levels of the following micronutrients were significantly different between cases
      and controls: calcium (7.48 +/- 2.16 versus 8.29 +/- 1.62 mg/dL; P = 0.04),
      manganese (44.1 +/- 11.5 versus 49.3 +/- 7.9 mg/L; P = 0.01), selenium (76.1 +/-
      14.9 versus 63.3 +/- 26.8 MUg/L; P = 0.02), and albumin (3.45 +/- 0.90 versus
      3.91 +/- 0.99 g/dL; P = 0.04). Plasma concentrations of iron and selenium were
      positively correlated with lung function, r = 0.43 (P < 0.05 in each case) while
      manganese serum concentration was negatively correlated with asthma (r = -0.44; P
      < 0.05). Conclusions. Children with asthma had reduced levels of plasma
      manganese, calcium, and albumin but raised level of selenium. The protective or
      risk effects of these micronutrients on asthma warrant further investigation. 

PMID- 26317028
TI  - Day to Day Variability and Reliability of Blood Oxidative Stress Markers within a
      Four-Week Period in Healthy Young Men.
AB  - The present study aimed to determine the day to day variability and reliability
      of several blood oxidative stress markers at rest in a healthy young cohort over
      a four-week period. Twelve apparently healthy resistance trained males (24.6 +/-
      3.0 yrs) were tested over 7 visits within 4 weeks with at least 72 hrs between
      visits at the same time of day. Subjects rested 30 minutes prior to blood being
      obtained by vacutainer. Results. The highest IntraClass correlations (ICC's) were
      obtained for protein carbonyls (PC) and oxygen radical absorbance capacity (ORAC)
      (PC = 0.785 and ORAC = 0.780). Cronbach's alpha reliability score for PC was
      0.967 and for ORAC was 0.961. The ICC's for GSH, GSSG, and the GSSG/TGH ratio ICC
      were 0.600, 0.573, and 0.570, respectively, with Cronbach's alpha being 0.913,
      0.904, and 0.903, respectively. Xanthine oxidase ICC was 0.163 and Cronbach's
      alpha was 0.538. Conclusions. PC and ORAC demonstrated good to excellent
      reliability while glutathione factors had poor to excellent reliability. Xanthine
      oxidase showed poor reliability and high variability. These results suggest that
      the PC and ORAC markers were the most stable and reliable oxidative stress
      markers in blood and that daily changes across visits should be considered when
      interpreting resting blood oxidative stress markers. 

PMID- 26317029
TI  - A Panel of Cancer Testis Antigens and Clinical Risk Factors to Predict Metastasis
      in Colorectal Cancer.
AB  - Colorectal cancer (CRC) is the third common carcinoma with a high rate of
      mortality worldwide and several studies have investigated some molecular and
      clinicopathological markers for diagnosis and prognosis of its malignant
      phenotypes. The aim of this study is to evaluate expression frequency of PAGE4,
      SCP-1, and SPANXA/D cancer testis antigen (CTA) genes as well as some clinical
      risk markers to predict liver metastasis of colorectal cancer patients. The
      expression frequency of PAGE4, SCP-1, and SPANXA/D cancer/testis antigen (CTA)
      genes was obtained using reverse transcription polymerase chain reaction (RT-PCR)
      assay in 90 colorectal tumor samples including both negative and positive liver
      metastasis tumors. Statistical analysis was performed to assess the association
      of three studied genes and clinical risk factors with CRC liver metastasis. The
      frequency of PAGE4 and SCP-1 genes expression was significantly higher in the
      primary tumours with liver metastasis when statistically compared with primary
      tumors with no liver metastasis (P < 0.05). Among all clinical risk factors
      studied, the lymph node metastasis and the depth of invasion were statistically
      correlated with liver metastasis of CRC patients. In addition, using multiple
      logistic regression, we constructed a model based on PAGE4 and lymph node
      metastasis to predict liver metastasis of CRC. 

PMID- 26317030
TI  - A Study on MTHFR C677T Gene Polymorphism and Alcohol Dependence among Meiteis of
      Manipur, India.
AB  - Chronic alcohol consumption is reported to be associated with increase in plasma
      homocysteine levels which is further influenced by the polymorphism in
      methylenetetrahydrofolate reductase (MTHFR) gene. The present study aims to
      understand the extent of the MTHFR C677T polymorphism in alcohol dependent (AD)
      cases of Meiteis of Manipur, a Mendelian population of India. MTHFR C677T
      polymorphism was screened in 313 controls and 139 alcohol dependent (AD) cases
      who all met DSM-IV criteria for alcohol dependence. Both AD cases and controls
      were unrelated up to 1st cousin. Among the control group, different drinking
      patterns like abstainer/nondrinkers (NDs), occasional drinkers (ODs), and
      moderate drinkers (MDs) are included. Both the groups were found to be in Hardy
      Weinberg equilibrium (P > 0.05). Genotypic and allelic frequency distribution of
      MTHFR C677T polymorphism did not differ significantly between AD cases and
      controls (P > 0.05). However, individuals carrying mutant (T) allele show more
      than 1-fold increased risk for AD though not significant (OR = 1.43; 95% CI 0.41
      5.01, P > 0.05). In conclusion, MTHFR C677T polymorphism is not found to be risk
      marker for AD in present studied population. However, higher prevalence of the
      mutant T allele may exacerbate deleterious health risk in future especially among
      alcohol drinkers. 

PMID- 26317032
TI  - Functional Epigenetic Analysis of Prostate Carcinoma: A Role for Seryl-tRNA
      Synthetase?
AB  - Transcriptional silencing, as a result of aberrant promoter hypermethylation, is
      a common mechanism through which genes in cancer cells become inactive.
      Functional epigenetic screens using demethylating agents to reexpress
      transcriptional silenced genes may identify such inactivated genes for needing
      further evaluation. We aimed to identify genes so far not known to be inactivated
      by promoter hypermethylation in prostate cancer. DU-145 and LNCaP cells were
      treated with the DNMT inhibitor zebularine. Expression changes of total RNA from
      treated and untreated cells were compared using an RNA expression microarray.
      Genes upregulated more than 2-fold were evaluated by RT-qPCR in 50 cases of
      paired normal and tumor tissues of prostate cancer patients. SARS was found to be
      downregulated in prostate cancer in 42/50 cases (84%). In addition, GADD45A and
      SPRY4 showed a remarkable diminished expression (88% and 74%, resp.). The gold
      standard for promoter hypermethylation-inactivated genes in prostate cancer
      (GSTP1) was repressed in 90% of our patient samples. ROC analyses reported
      statistically significant AUC curves in SARS, GADD45A, and GSTP1 and positive
      Spearman correlations were found between these genes. SARS was discovered to be a
      novel gene that is repressed in prostate cancer and could therefore be
      recommended for its involvement in prostate carcinogenesis. 

PMID- 26317033
TI  - Portable XRF Technology to Quantify Pb in Bone In Vivo.
AB  - Lead is a ubiquitous toxicant. Bone lead has been established as an important
      biomarker for cumulative lead exposures and has been correlated with adverse
      health effects on many systems in the body. K-shell X-ray fluorescence (KXRF) is
      the standard method for measuring bone lead, but this approach has many
      difficulties that have limited the widespread use of this exposure assessment
      method. With recent advancements in X-ray fluorescence (XRF) technology, we have
      developed a portable system that can quantify lead in bone in vivo within 3
      minutes. Our study investigated improvements to the system, four calibration
      methods, and system validation for in vivo measurements. Our main results show
      that the detection limit of the system is 2.9 ppm with 2 mm soft tissue
      thickness, the best calibration method for in vivo measurement is background
      subtraction, and there is strong correlation between KXRF and portable LXRF bone
      lead results. Our results indicate that the technology is ready to be used in
      large human population studies to investigate adverse health effects of lead
      exposure. The portability of the system and fast measurement time should allow
      for this technology to greatly advance the research on lead exposure and
      public/environmental health. 

PMID- 26317031
TI  - A Quest to Identify Prostate Cancer Circulating Biomarkers with a Bench-to
      Bedside Potential.
AB  - Prostate cancer (PCA) is a major health concern in current times. Ever since
      prostate specific antigen (PSA) was introduced in clinical practice almost three
      decades ago, the diagnosis and management of PCA have been revolutionized. With
      time, concerns arose as to the inherent shortcomings of this biomarker and
      alternatives were actively sought. Over the past decade new PCA biomarkers have
      been identified in tissue, blood, urine, and other body fluids that offer
      improved specificity and supplement our knowledge of disease progression. This
      review focuses on superiority of circulating biomarkers over tissue biomarkers
      due to the advantages of being more readily accessible, minimally invasive
      (blood) or noninvasive (urine), accessible for sampling on regular intervals, and
      easily utilized for follow-up after surgery or other treatment modalities. Some
      of the circulating biomarkers like PCA3, IL-6, and TMPRSS2-ERG are now detectable
      by commercially available kits while others like microRNAs (miR-21, -221, -141)
      and exosomes hold potential to become available as multiplexed assays. In this
      paper, we will review some of these potential candidate circulating biomarkers
      that either individually or in combination, once validated with large-scale
      trials, may eventually get utilized clinically for improved diagnosis, risk
      stratification, and treatment. 

PMID- 26317034
TI  - Urinary beta2-Microglobulin Is a Good Indicator of Proximal Tubule Injury: A
      Correlative Study with Renal Biopsies.
AB  - Objective. After filtration through glomeruli, beta2-microglobulin is reabsorbed
      in proximal tubules. Increased urinary beta2-microglobulin indicates proximal
      tubule injury and measurement of beta2-microglobulin in urine is useful to
      determine the source of renal injury. Kidney injury molecule-1 (KIM-1) has been
      characterized as a selective proximal tubule injury marker. This study was
      designed to evaluate the correlation of urinary beta2-microglobulin concentration
      and KIM-1 expression as evidence of proximal tubule injury. Methods. Between 2009
      and 2012, 46 patients with urine beta2-microglobulin (RenalVysion) had follow-up
      kidney biopsy. Diagnoses included glomerular and tubule-interstitial disease.
      Immunohistochemical staining for KIM-1 was performed and the intensity was graded
      from 0 to 3+. Linear regression analysis was applied to correlate the values of
      urinary beta2-microglobulin and KIM-1 staining scores. P < 0.05 was considered
      statistically significant. Results. Thirty patients had elevated urinary beta2
      microglobulin. KIM-1 staining was positive in 35 kidney biopsies. There was a
      significant correlation between urinary beta2-microglobulin and KIM-1 staining (P
      < 0.05). Sensitivity was 86.6%, specificity was 43.7%, positive predictive value
      was 74.2%, and negative predictive value was 63.6%. Conclusion. Increased urinary
      beta2-microglobulin is significantly correlated with KIM-1 staining in injured
      proximal tubules. Measurement of urine beta2-microglobulin is a sensitive assay
      for proximal tubule injury. 

PMID- 26317035
TI  - Biomarkers Predict Relapse in Granulomatosis with Polyangiitis.
AB  - Granulomatosis with polyangiitis (GPA) is a small blood vessel vasculitic
      disorder with a high mortality rate if undiagnosed or treated inadequately.
      Disease relapse is a key feature of this disease and early identification of
      relapse episodes is very important in limiting end-organ damage. The advent of
      indirect immunofluorescence to detect antineutrophil cytoplasmic antibody (ANCA)
      with specific reactivity against the enzyme proteinase-3 (PR3) has been very
      useful in the diagnosis of GPA but is less helpful in predicting relapse. Indeed,
      up to date no satisfactory biomarker has been identified that can reliably
      predict relapse. This study assessed the probability of the occurrence of a
      relapse when a change was noted in a range of commonly used laboratory tests.
      These tests included levels of C-reactive protein (CRP), anti-PR3 antibodies,
      ANCA titre, and the neutrophil count. A group of 30 GPA patients with a total of
      66 relapse episodes was investigated and a novel clinical yield score was
      devised. When a combined rise in CRP, anti-PR3 antibodies, and neutrophil count
      was observed in the 6-month period before a relapse event, 59% of patient
      relapses could be predicted. Monitoring changes in this set of parameters helps
      identify disease relapse. 

PMID- 26317036
TI  - Diagnosis of Non-ST-Elevation Acute Coronary Syndrome by the Measurement of Heart
      Type Fatty Acid Binding Protein in Serum: A Prospective Case Control Study.
AB  - A prospective case control study was undertaken to evaluate the diagnostic
      performance of serum heart-type fatty acid binding protein (HFABP) in comparison
      to cardiac TnT and TnI in 33 patients admitted with chest pain, diagnosed as NSTE
      ACS (non ST elevation acute coronary syndrome) and 22 healthy controls. Area
      under the receiver operating curve (AUC) was highest for H-FABP (AUC 0.79; 95% CI
      0.66-0.89) versus cTnI (AUC 0.73; 95% CI 0.59-0.84) and cTnT (AUC 0.71; 95% CI
      0.57-0.83). The H-FABP level above 6.5 ng/mL showed 56.7% (CI 37.4-74.5)
      sensitivity, 0.5 (95% CI 0.3-0.7) negative likelihood ratio (-LR), 100% (CI 84.6
      100.0) specificity, and 100% (CI 79.4-100.0) positive predictive value (PPV),
      62.9% (CI 44.9-78.5) negative predictive value (NPV). cTnI level above 0.009
      MUg/L had 40% (CI 22.7-59.4) sensitivity, 0.6 (95% CI 0.4-0.8) -LR, 100% (CI 84.6
      100.0) specificity, 100% (CI 73.5-100.0) PPV, and 55% (CI 38.5-70.7) NPV. cTnT
      showed 46.7% (CI 28.3-65.7) sensitivity, 0.5 (95% CI 0.4-0.7) -LR, 100% (CI 84.6
      100.0) specificity, 100% (CI 76.8-100.0) PPV, and 57.9% (CI 40.8-73.7) NPV at
      level above 9 MUg/L. +LR were 12.5 (95% CI 1.8-86.8), 1.7 (95% CI 1.0-3.0), and
      1.2 (95% CI 0.8-1.9) for H-FABP, cTnI, and cTnT respectively. In conclusion
      measurement of H-FABP is a valuable tool in the early diagnosis of patients with
      chest pain (6-8 hrs) and seems to be a preferred biomarker in the differential
      diagnosis of NSTE-ACS. More studies are needed to determine whether serum H-FABP
      further improves diagnostic performance. 

PMID- 26317037
TI  - In Search of Biomarkers for Idiopathic Scoliosis: Leptin and BMP4 Functional
      Polymorphisms.
AB  - Idiopathic scoliosis (IS) is the most common spinal disorder in children and
      adolescents. The current consensus on IS maintains that it has a multifactorial
      etiology with genetic predisposition factors. In the present study the
      association of two functional polymorphisms of leptin (rs7799039) and BMP4
      (rs4898820) with susceptibility to IS and curve severity was investigated in a
      Bulgarian population sample. The molecular detection of the genotypes was
      performed by amplification followed by restriction technology. The statistical
      analysis was performed by Pearson's chi-squared test. This case-control study
      revealed no statistically significant association between the functional
      polymorphisms of leptin and BMP4 and susceptibility to IS or curve progression (p
      > 0.05). On the basis of these results the examined polymorphic variants of
      leptin and BMP4 could not be considered as genetic variants with predisposition
      effect or as risk factors for the progression of the curve. In addition, these
      results do not exclude a synergistic effect of the promoter polymorphisms of
      leptin and BMP4 in the etiology and pathogenesis of IS. The identification of
      molecular markers for IS could be useful for early detection and prognosis of the
      risk for a rapid progression of the curve. That would permit early stage
      treatment of the patient with the least invasive procedures. 

PMID- 26317038
TI  - Biomarkers for Detection and Monitoring of B16 Melanoma in Mouse Urine and Feces.
AB  - Melanoma is the most malignant type of skin cancer. Early detection of melanoma
      is thus critical for patient prognosis and survival. At present, examination by a
      skilled dermatologist followed by biopsy of suspicious lesions is the diagnostic
      gold standard. The aim of the present study was to examine an alternative and
      noninvasive method for the diagnosis of melanoma at an early stage. We identified
      and compared the volatile organic compounds (VOCs) in mouse urine and feces,
      before and after a subcutaneous injection of B16 melanoma cells. We identified a
      total of 16 VOCs in urine and 13 VOCs in feces that could serve as potential
      biomarkers. Statistical analysis significantly discriminated between the cancer
      and control groups. These results should be validated in a larger-scale animal
      study, after which a study could be designed in patients to develop a melanoma
      biomarker. 

PMID- 26317040
TI  - Fenxiang biota: a new Early Ordovician shallow-water fauna with soft-part
      preservation from China.
AB  - Our perception of biodiversity in the geological past is incomplete and biased
      because most organisms did not have mineralized skeletons and therefore had
      little chance of fossilization. This especially refers to shallow-water marine
      environments, rarely represented by localities with exceptional preservation of
      fossil material (known as taphonomic windows or Konservat-Lagerstatten). Such
      extraordinary "windows" may markedly broaden our knowledge of biodiversity of the
      past. Here, we show a review of the invertebrate fossils from recently discovered
      locality in the Lower Ordovician Fenxiang Formation of Hubei Province in southern
      China revealing exceptional preservation of soft tissues. The fauna, generally of
      shallow-water aspect, contains linguloid brachiopods with a remarkably preserved
      pedicle, the oldest traces of nematode life activities, the oldest reliable
      record of hydroids, the first fossil antipatharian corals, a pyritized colonial
      organism of unknown affinity, supposed arthropod appendages, probable
      phosphatized scalidophoran worm embryo and other fossils. Our discovery supports
      the opinion that the famous soft-bodied preservation of Burgess Shale- or
      Chengjiang-type did not vanish from the fossil record in post-Cambrian times. The
      new finding represents a prelude to the Great Ordovician Biodiversification Event
      and provides evidence for calibration of molecular clock of several invertebrate
      lineages.

PMID- 26317039
TI  - Current Challenges in Volatile Organic Compounds Analysis as Potential Biomarkers
      of Cancer.
AB  - An early diagnosis and appropriate treatment are crucial in reducing mortality
      among people suffering from cancer. There is a lack of characteristic early
      clinical symptoms in most forms of cancer, which highlights the importance of
      investigating new methods for its early detection. One of the most promising
      methods is the analysis of volatile organic compounds (VOCs). VOCs are a diverse
      group of carbon-based chemicals that are present in exhaled breath and biofluids
      and may be collected from the headspace of these matrices. Different patterns of
      VOCs have been correlated with various diseases, cancer among them. Studies have
      also shown that cancer cells in vitro produce or consume specific VOCs that can
      serve as potential biomarkers that differentiate them from noncancerous cells.
      This review identifies the current challenges in the investigation of VOCs as
      potential cancer biomarkers, by the critical evaluation of available matrices for
      the in vivo and in vitro approaches in this field and by comparison of the main
      extraction and detection techniques that have been applied to date in this area
      of study. It also summarises complementary in vivo, ex vivo, and in vitro studies
      conducted to date in order to try to identify volatile biomarkers of cancer. 

PMID- 26317041
TI  - Monocyte-Induced Prostate Cancer Cell Invasion is Mediated by Chemokine ligand 2
      and Nuclear Factor-kappaB Activity.
AB  - STUDY BACKGROUND: The tumor microenvironment contains inflammatory cells which
      can influence cancer growth and progression; however the mediators of these
      effects vary with different cancer types. The mechanisms by which prostate cancer
      cells communicate with monocytes to promote cancer progression are incompletely
      understood. This study tested prostate cancer cell and monocyte interactions that
      lead to increased prostate cancer cell invasion. METHODS: We analyzed the
      prostate cancer cell invasion and NF-kappaB activity and cytokine expression
      during interaction with monocyte-lineage cells in co-cultures. The roles of
      monocyte chemotactic factor (MCP-1/CCL2) and NF-kappaB activity for co-culture
      induced prostate cancer invasion were tested. Clinical prostate cancer NF-kappaB
      expression was analyzed by immunohistochemistry. RESULTS: In co-cultures of
      prostate cancer cell lines with monocyte-lineage cells, (C-C motif) ligand 2
      (CCL2) levels were significantly increased when compared with monocytes or cancer
      cells cultured alone. Prostate cancer cell invasion was induced by recombinant
      CCL2 in a dose dependent manner, similar to co-cultures with monocytes. The
      monocyte-induced prostate cancer cell invasion was inhibited by CCL2 neutralizing
      antibodies and by the CCR2 inhibitor, RS102895. Prostate cancer cell invasion and
      CCL2 expression induced in the co-cultures was inhibited by Lactacystin and Bay11
      7082 NF-kappaB inhibitors. Prostate cancer cell NF-kappaB DNA binding activity
      depended on CCL2 dose and was inhibited by CCL2 neutralizing antibodies. Clinical
      prostate cancer NF-kappaB expression correlated with tumor grade. CONCLUSIONS: Co
      cultures with monocyte-lineage cell lines stimulated increased prostate cancer
      cell invasion through increased CCL2 expression and increased prostate cancer
      cell NF-kappaB activity. CCL2 and NF-kappaB may be useful therapeutic targets to
      interfere with inflammation-induced prostate cancer invasion.

PMID- 26317042
TI  - Orthostatic Tremor: A Spectrum of Fast and Slow Frequencies or Distinct Entities?
AB  - BACKGROUND: Orthostatic tremor (OT) is defined by the presence of a high
      frequency (13-18 Hz) tremor of the legs upon standing associated with a feeling
      of unsteadiness. However, some patients have discharge frequencies of <13 Hz, so
      called "slow OT". The aim of this study was to characterize patients with
      unsteadiness upon standing found to have <13 Hz tremor discharges on
      neurophysiologic testing. METHODS: A retrospective review was performed on all
      subjects with a diagnosis of OT who were referred to the Mayo Clinic, Scottsdale,
      AZ, between 1999 and 2013 for confirmation using neurophysiology. RESULTS:
      Fourteen of 28 subjects (50%) had OT discharges of <13 Hz, of whom eight had
      frequencies of <10 Hz and six had frequencies of 10-13 Hz. Lower frequency
      discharges tended to have a broader spectral peak, greater variability in
      discharge duration, and lower inter-muscular coherence. Subjects with <13 Hz OT
      had shorter mean disease duration at time of neurophysiology testing (2.00 years
      in <10 Hz group, 7.96 years 10-13 Hz group, and 11.43 years >13 Hz; p = 0.002).
      The proportion of subjects who experienced gait unsteadiness (85.7% vs. 66.6% vs.
      21.4%; p = 0.016), falls (37.5% vs. 50% vs. 0%; p = 0.010), and had abnormal gait
      on examination (71.4% vs. 66.0% vs. 14.3%; p = 0.017) was greater in those with
      low and intermediate frequencies. DISCUSSION: Slow tremor electromyography
      frequencies (<13 Hz) may characterize a substantial proportion of patients
      labeled as OT. These subjects may have greater gait involvement and higher
      likelihood of falls leading to earlier presentation to subspecialty care.

PMID- 26317043
TI  - Neuroacanthocytosis: Observations, Theories and Perspectives on the Origin and
      Significance of Acanthocytes.
AB  - The presence of acanthocytes in the blood is characteristic of patients suffering
      from neuroacanthocytosis (NA). Recent studies have described abnormal
      phosphorylation of the proteins involved in connecting the membrane and
      cytoskeleton in patient-derived erythrocytes. The involvement of lipids in the
      underlying signaling pathways and recent reports on in vitro disease-associated
      lipid alterations support renewed research into lipid composition, signal
      transduction, and metabolism in patient erythrocytes. In addition to morphology,
      changes in membrane organization affect erythrocyte function and survival.
      Patient erythrocytes may have a decreased ability to deform, and this may
      contribute to accelerated erythrocyte removal and a decreased oxygen supply,
      especially in vulnerable brain regions. The presently available data indicate
      that acanthocytes are likely to originate in the bone marrow, making
      erythropoiesis an obvious new focus in NA research. Moreover, new, detailed
      morphological observations indicate that acanthocytes may be the tip of the
      iceberg with regard to misshapen erythrocytes in the circulation of patients with
      NA. A systematic assessment of patient erythrocyte morphology, deformability,
      oxygen delivery, and metabolism will be instrumental in determining the putative
      contribution of erythrocyte function to NA clinical symptoms. 

PMID- 26317044
TI  - Defining the Treatment Gap: What Essential Tremor Patients Want That They Are Not
      Getting.
AB  - BACKGROUND: Patient-centeredness (i.e., providing care that is responsive to
      individual patient preferences) is increasingly recognized as a crucial element
      of quality of care. METHODS: A six-item patient-centeredness questionnaire was
      devised to assess the self-perceived needs of essential tremor (ET) patients. A
      link to the questionnaire was included in the monthly e-newsletter of the
      International Essential Tremor Foundation. The questionnaires were completed
      online and data were available in electronic format. RESULTS: There were 1,418
      respondents. One in three respondents (i.e., 31.4%) indicated that the doctor was
      not even "moderately well-educated" about ET. Only 11.8% of respondents were
      satisfied with their care. Respondents raised a multiplicity of issues that were
      not being addressed in their current care. The top items were psychological
      services and support (33.9%), physical or occupational therapy (28.6%), handling
      embarrassment and social effects of tremor (15.8%), feelings of not being in
      control (13.7%), a detailed report and a more quantitative way of assessing
      tremor and tracking progression (12.7%), better counseling about current
      treatment and medications (11.9%), empathy, compassion and a feeling of being
      heard (11.6%), a treatment approach other than just medications and surgery
      (11.2%), and a discussion of all symptoms aside from tremor (e.g., cognition,
      balance). DISCUSSION: Patients with ET identified a broad range of issues that
      they felt were not addressed in their treatment; indeed, only one in 10 patients
      reported that they were satisfied with their care. It is hoped that patient
      centered approaches such as this will lead to improved models for the care of
      patients with this common chronic disease.

PMID- 26317045
TI  - Memantine-induced Myoclonus in a Patient with Alzheimer Disease.
AB  - BACKGROUND: Myoclonus can be a clinical manifestation of numerous
      neurodegenerative disorders and an adverse drug reaction to medications used in
      their treatment. CASE REPORT: Herein, we report memantine-induced myoclonus in a
      patient with Alzheimer disease. The myoclonus seen in our patient was generalized
      (proximal limbs and trunk), present at rest and with action, and stimulus
      sensitive. A structured evaluation with the Unified Myoclonus Rating Scale showed
      that the myoclonus had no significant effect on functional capacity. After
      discontinuation of memantine, myoclonus slowly resolved over the course of
      several weeks. DISCUSSION: Memantine may cause myoclonus in susceptible
      individuals.

PMID- 26317046
TI  - In this issue of Adipocyte.

PMID- 26317047
TI  - Adipose depots differ in cellularity, adipokines produced, gene expression, and
      cell systems.
AB  - The race to manage the health concerns related to excess fat deposition has
      spawned a proliferation of clinical and basic research efforts to understand
      variables including dietary uptake, metabolism, and lipid deposition by
      adipocytes. A full appreciation of these variables must also include a depot
      specific understanding of content and location in order to elucidate mechanisms
      governing cellular development and regulation of fat deposition. Because adipose
      tissue depots contain various cell types, differences in the cellularity among
      and within adipose depots are presently being documented to ascertain functional
      differences. This has led to the possibility of there being, within any one
      adipose depot, cellular distinctions that essentially result in adipose depots
      within depots. The papers comprising this issue will underscore numerous
      differences in cellularity (development, histogenesis, growth, metabolic
      function, regulation) of different adipose depots. Such information is useful in
      deciphering adipose depot involvement both in normal physiology and in pathology.
      Obesity, diabetes, metabolic syndrome, carcass composition of meat animals,
      performance of elite athletes, physiology/pathophysiology of aging, and numerous
      other diseases might be altered with a greater understanding of adipose depots
      and the cells that comprise them-including stem cells-during initial development
      and subsequent periods of normal/abnormal growth into senescence. Once thought to
      be dormant and innocuous, the adipocyte is emerging as a dynamic and influential
      cell and research will continue to identify complex physiologic regulation of
      processes involved in adipose depot physiology. 

PMID- 26317049
TI  - The cellularity of offspring's adipose tissue is programmed by maternal
      nutritional manipulations.
AB  - Epidemiological studies initially demonstrated that maternal undernutrition leads
      to low birth weight with increased risk of adult-onset obesity. Maternal obesity
      and diabetes associated with high birth weight, excessive nutrition in neonates,
      and rapid catch-up growth also predispose offspring to fat accumulation. As
      stated by the Developmental Origin of Health and Disease concept, nutrient supply
      perturbations in the fetus or neonate result in long-term programming of
      individual body weight set-point. Adipose tissue is a key fuel storage unit
      mainly involved in the maintenance of energy homeostasis. Studies in numerous
      animal models have demonstrated that the adipose tissue is the focus of
      developmental programming events in a gender- and depot-specific manner. This
      review summarizes the impact of maternal nutritional manipulations on cellularity
      (i.e., cell number, size, and type) of adipose tissue in programmed offspring. In
      rodents, adipose tissue development is particularly active during the perinatal
      period, especially during the last week of gestation and during early postnatal
      life. In contrast to rodents, this process essentially takes place before birth
      in bigger mammals. Despite these different developmental time windows, altricial
      and precocial species share several mechanisms of adipose tissue programming.
      Maternal nutritional manipulations result in increased adipogenesis and modified
      fat distribution and composition. Inflammation changes such as infiltration of
      macrophages and increased inflammatory markers are also observed. Overall, it may
      predispose offspring to fat accumulation and obesity. Inappropriate hormone
      levels, modified tissue sensitivity, and epigenetic mechanisms are key factors
      involved in the programming of adipose tissue's cellularity during the perinatal
      period. 

PMID- 26317048
TI  - Intermuscular and intramuscular adipose tissues: Bad vs. good adipose tissues.
AB  - Human studies of the influence of aging and other factors on intermuscular fat
      (INTMF) were reviewed. Intermuscular fat increased with weight loss, weight gain,
      or with no weight change with age in humans. An increase in INTMF represents a
      similar threat to type 2 diabetes and insulin resistance as does visceral adipose
      tissue (VAT). Studies of INTMF in animals covered topics such as quantitative
      deposition and genetic relationships with other fat depots. The relationship
      between leanness and higher proportions of INTMF fat in pigs was not observed in
      human studies and was not corroborated by other pig studies. In humans, changes
      in muscle mass, strength and quality are associated with INTMF accretion with
      aging. Gene expression profiling and intrinsic methylation differences in pigs
      demonstrated that INTMF and VAT are primarily associated with inflammatory and
      immune processes. It seems that in the pig and humans, INTMF and VAT share a
      similar pattern of distribution and a similar association of components dictating
      insulin sensitivity. Studies on intramuscular (IM) adipocyte development in meat
      animals were reviewed. Gene expression analysis and genetic analysis have
      identified candidate genes involved in IM adipocyte development. Intramuscular
      (IM) adipocyte development in human muscle is only seen during aging and some
      pathological circumstance. Several genetic links between human and meat animal
      adipogenesis have been identified. In pigs, the Lipin1 and Lipin 2 gene have
      strong genetic effects on IM accumulation. Lipin1 deficiency results in immature
      adipocyte development in human lipodystrophy. In humans, overexpression of
      Perilipin 2 (PLIN2) facilitates intramyocellular lipid accretion whereas in pigs
      PLIN2 gene expression is associated with IM deposition. Lipins and perilipins may
      influence intramuscular lipid regardless of species. 

PMID- 26317051
TI  - Particle size in fat graft retention: A review on the impact of harvesting
      technique in lipofilling surgical outcomes.
AB  - Fat grafting popularity continues to rise among plastic surgeons. As a soft
      tissue filler, adipose tissue had many desirable attributes: it is easy to
      obtain, autologous, and may reintegrate into recipient sites. However, fat
      grafting is clinically plagued by unpredictable resorption rates, thus there is
      much interest in optimizing the procedure of fat grafting for consistent graft
      volumes. Fat harvesting, a part of fat transfer surgery, involves the removal of
      adipose tissue from the donor site. Different harvest procedures, such as whole
      fat excision or liposuction cannulas, result in a range of fat particle volumes,
      which may play a role in the cellular stability of grafts. The ideal harvesting
      technique and fat particle diameter is not currently known. This study aims to
      review the literature on the impact of fat particle size and clinical fat
      grafting outcomes, to present overarching conclusions, and to provide future
      directions for study. Current evidence supports excisional methods and larger
      bore cannulas to minimize cellular damage, preserve the native architecture, and
      maximize the number of cells within fat particles. 

PMID- 26317050
TI  - Pathophysiological role of enhanced bone marrow adipogenesis in diabetic
      complications.
AB  - Diabetes leads to complications in select organ systems primarily by disrupting
      the vasculature of the target organs. These complications include both micro-
      (cardiomyopathy, retinopathy, nephropathy, and neuropathy) and macro
      (atherosclerosis) angiopathies. Bone marrow angiopathy is also evident in both
      experimental models of the disease as well as in human diabetes. In addition to
      vascular disruption, bone loss and increased marrow adiposity have become
      hallmarks of the diabetic bone phenotype. Emerging evidence now implicates
      enhanced marrow adipogenesis and changes to cellular makeup of the marrow in a
      novel mechanistic link between various secondary complications of diabetes. In
      this review, we explore the mechanisms of enhanced marrow adipogenesis in
      diabetes and the link between changes to marrow cellular composition, and
      disruption and depletion of reparative stem cells. 

PMID- 26317053
TI  - Prostaglandin E2 signals white-to-brown adipogenic differentiation.
AB  - The formation of new adipocytes from precursor cells is a crucial aspect of
      normal adipose tissue function. During the adipogenic process, adipocytes
      differentiated from mesenchymal stem cells give rise to two main types of fat:
      white adipose tissue (WAT) characterized by the presence of adipocytes containing
      large unilocular lipid droplets, and brown adipose tissue (BAT) composed by
      multilocular brown adipocytes packed with mitochondria. WAT is not only important
      for energy storage but also as an endocrine organ regulating whole body
      homeostasis by secreting adipokines and other mediators, which directly impact
      metabolic functions in obesity. By contrast, BAT is specialized in dissipating
      energy in form of heat and has salutary effects in combating obesity and
      associated disorders. Unfortunately, WAT is the predominant fat type, whereas BAT
      is scarce and located in discrete pockets in adult humans. Luckily, another type
      of brown adipocytes, called beige or brite (brown-in-white) adipocytes, with
      similar functions to those of "classical" brown adipocytes has recently been
      identified in WAT. In this review, a close look is given into the role of
      bioactive lipid mediators in the regulation of adipogenesis, with a special
      emphasis on the role of the microsomal prostaglandin E (PGE) synthase-1, a
      terminal enzyme in PGE2 biosynthesis, as a key regulator of white-to-brown
      adipogenesis in WAT. 

PMID- 26317052
TI  - Fighting obesity: When muscle meets fat.
AB  - The prevalence of obesity has risen to an unprecedented level. According to World
      Health Organization, over 500 million adults, equivalent to 10%-14% of the world
      population, were obese with a body mass index (BMI) of 30 kg/m(2) or greater in
      2008.(1) This rising prevalence and earlier onset of obesity is believed to be
      resulted from an interplay of genetic factors, over-nutrition and physical
      inactivity in modern lifestyles. Obesity also increases the susceptibility to
      metabolic syndromes, hypertension, cardiovascular diseases, Type 2 diabetes
      mellitus (T2DM) and cancer.(2-4) The global obesity epidemic has sparked
      substantial interests in the biology of adipose tissue (fat). In addition, the
      skeletal muscle and its secretive factors (myokines) have also been shown to play
      a critical role in controlling body energy balance, adipose homeostasis and
      inflammation status.(5) Interestingly, skeletal muscle cells share a common
      developmental origin with brown adipocytes,(6,7) which breaks down lipids to
      generate heat - thus reducing obesity. Here, we provide a brief overview of the
      basics and recent progress in muscle-fat crosstalk in the context of body energy
      metabolism, obesity, and diabetes. We summarize the different types of
      adipocytes, their developmental origins and implications in body composition. We
      highlight the role of several novel myokines in regulating fat mass and systemic
      energy balance, and evaluate the potential of skeletal muscles as a therapeutic
      target to treat obesity. 

PMID- 26317054
TI  - Gene expression profiling in adipose tissue from growing broiler chickens.
AB  - In this study, total RNA was collected from abdominal adipose tissue samples
      obtained from ten broiler chickens at 3, 4, 5, and 6 weeks of age and prepared
      for gene microarray analysis with Affymetrix GeneChip Chicken Genome Arrays
      (Affymetrix) and quantitative real-time PCR analysis. Studies of global gene
      expression in chicken adipose tissue were initiated since such studies in many
      animal species show that adipose tissue expresses and secretes many factors that
      can influence growth and physiology. Microarray results indicated 333
      differentially expressed adipose tissue genes between 3 and 6 wk, 265
      differentially expressed genes between 4 and 6 wk and 42 differentially expressed
      genes between 3 and 4 wk. Enrichment scores of Gene Ontology Biological Process
      categories indicated strong age upregulation of genes involved in the immune
      system response. In addition to microarray analysis, quantitative real-time PCR
      analysis was used to confirm the influence of age on the expression of adipose
      tissue CC chemokine ligands (CCL), toll-like receptor (TLR)-2, lipopolysaccharide
      induced TNF factor (LITAF), chemokine (C-C motif) receptor 8 (CCR8), and several
      other genes. Between 3 and 6 wk of age CCL5, CCL1, and CCR8 expression increased
      (P = 0.0001) with age. Furthermore, TLR2, CCL19, and LITAF expression increased
      between 4 and 6 wk of age (P = 0.001). This is the first demonstration of age
      related changes in CCL, LITAF, and TLR2 gene expression in chicken adipose
      tissue. Future studies are needed to elucidate the role of these adipose tissue
      genes in growth and the immune system. 

PMID- 26317055
TI  - Nutritional milieu of isolated stromal vascular cells determines their
      proliferative, adipogenic, and lipogenic capacity in vitro.
AB  - The objective was to determine the effect of nutritional milieu of isolated
      stromal vascular (SV) cells on proliferative capacity of preadipocytes, and
      adipogenic and lipogenic capacity in adipocytes in vitro. Proliferation of the
      preadipocytes increased over time with 48 and 72 h being greater than 24 h;
      however, preadipocytes from steers supplemented with corn (LC) had lower
      proliferation rates compared with those without corn grain supplementation (L) at
      72 h. Adipocyte cultures isolated from LC group had higher mean diameter on d 4
      and 6, and higher mean volume on d 0, 4, 6, and 12 of culture. Adipocytes from
      steers supplemented with corn grain (LC) had lower expression of key adipogenic
      genes during extended days in culture. The results show that prior nutritional
      treatment of the donor animal used to isolate SV cultures alters their
      proliferative, adipogenic, and lipogenic capacity in culture. These differences
      may be related to lower induction/expression of AP2 gene in the adipose cultures
      from corn supplemented group. Corn grain supplementation to steers grazing
      legumes could have stimulated more active adipogenic progenitor cells to
      differentiate, which would leave fewer behind in the SV pool for subsequent
      isolation. 

PMID- 26317056
TI  - Amelioration of insulin resistance by rosiglitazone is associated with increased
      adipose cell size in obese type 2 diabetic patients.
AB  - Early studies reported that the size of adipose cells positively correlates with
      insulin resistance, but recent evidence suggests that the relationship between
      adipose cell size and insulin resistance is more complex. We previously reported
      that among BMI-matched moderately obese subjects who were either insulin
      sensitive or resistant insulin resistance correlated with the proportion of small
      adipose cells, rather than the size of the large adipose cells, whereas the size
      of large adipose cells was found to be a predictor of insulin resistance in the
      first-degree relatives of type 2 diabetic (T2D) patients. The relationship
      between adipose cellularity and insulin resistance thus appears to depend on the
      metabolic state of the individual. We did a longitudinal study with T2D patients
      treated with the insulin-sensitizer rosiglitazone to test the hypothesis that
      improved insulin sensitivity is associated with increased adipocyte size. Eleven
      T2D patients were recruited and treated with rosiglitazone for 90 days. Blood
      samples and needle biopsies of abdominal subcutaneous fat were taken at six time
      points and analyzed for cell size distributions. Rosiglitazone treatment
      ameliorated insulin resistance as evidenced by significantly decreased fasting
      plasma glucose and increased index of insulin sensitivity, QUICKI. In association
      with this, we found significantly increased size of the large adipose cells and,
      with a weaker effect, increased proportion of small adipose cells. We conclude
      rosiglitazone treatment both enlarges existing large adipose cells and recruits
      new small adipose cells in T2D patients, improving fat storage capacity in
      adipose tissue and thus systemic insulin sensitivity. 

PMID- 26317057
TI  - The proliferation and differentiation of primary pig preadipocytes is suppressed
      when cultures are incubated at 37 degrees Celsius compared to euthermic
      conditions in pigs.
AB  - Given similarities in metabolic parameters and cardiovascular physiology, the pig
      is well positioned as a biomedical model for metabolic disease and obesity in
      humans. Better understanding molecular mechanisms governing porcine adipocyte
      hyperplasia may provide insight into the regulation of adipose tissue development
      that is useful both when considering the pig as a commodity and when
      extrapolating porcine data to human disease. Primary cultures of pig stromal
      vascular cells have served as a useful tool for investigating factors that
      regulate preadipocyte proliferation and differentiation. However, such cultures
      have generally been maintained at 37 degrees C in vitro despite euthermia being
      39 degrees C in pigs. To address potential concerns about the physiological
      relevance of culturing primary pig preadipocytes under what would be hypothermic
      conditions in vivo, the objective of this study was to investigate the effect of
      culture temperature on the proliferation and differentiation of pig preadipocytes
      in primary culture. Culturing primary preadipocytes at 37 rather than 39 degrees
      C decreases their proliferation rates based upon cleavage of the tetrazolium
      salt, MTT (P < 0.001), reduction of resazurin (P < 0.001), and daily cell counts
      (P < 0.001). Likewise, culturing primary porcine preadipocytes at 37 degrees C
      suppressed their adipogenic potential based upon monitoring adipogenesis
      morphologically, biochemically, and via the expression of mRNA encoding
      adipogenic marker genes. Collectively, these data indicate the proliferation and
      differentiation of primary pig preadipocytes is suppressed when cultures are
      incubated at 37 degrees C compared to normal body temperature of pigs. This may
      confound investigation of factors that impact adipocyte hyperplasia in the pig. 

PMID- 26317059
TI  - Economic Evaluation of Fungal Meningitis Outbreak Response in New River Valley:
      Local Health Department Perspective.
AB  - BACKGROUND: The multi-state fungal meningitis outbreak started in September 2012
      in Tennessee. The cause of the outbreak was injection of contaminated lots of
      methylprednisolone acetate used in epidural spinal injections. Roanoke and New
      River Valley were the epicenter of this outbreak in Virginia, with two clinical
      centers having administered the contaminated injections to their patients. New
      River Health District, in coordination with hospitals, and state and federal
      agencies, deployed its resources to control the local impact of the outbreak.
      PURPOSE: The objective of this study was to conduct an economic evaluation of the
      fungal meningitis outbreak response in New River Valley of Virginia, from the
      local public health department perspective. METHODS: The health department
      conducted the outbreak investigation from October 2012 until March 2013 to
      ascertain that all possible cases were identified and treated. Data were
      collected on the costs associated with the local health department in the
      outbreak response, and the epidemiologic effectiveness estimated, using the
      metric of disability adjusted life years (DALYs). RESULTS: The cost incurred by
      the local health department was estimated to be $30,493; the epidemiologic
      effectiveness was estimated to be 138 DALYs averted among the patients, for an
      incremental cost-effectiveness ratio of $221 per DALY averted. IMPLICATIONS: The
      incremental cost effectiveness ratio of the fungal meningitis outbreak response
      in New River Valley assists the local health department to analyze the costs and
      epidemiologic effectiveness of the outbreak response.

PMID- 26317058
TI  - Role of histone deacetylase 9 in regulating adipogenic differentiation and high
      fat diet-induced metabolic disease.
AB  - Adipose tissue serves as both a storage site for excess calories and as an
      endocrine organ, secreting hormones such as adiponectin that promote metabolic
      homeostasis. In obesity, adipose tissue expands primarily by hypertrophy
      (enlargement of existing adipocytes) rather than hyperplasia (generation of new
      adipocytes via adipogenic differentiation of preadipocytes). Progressive
      adipocyte hypertrophy leads to inflammation, insulin resistance, dyslipidemia,
      and ectopic lipid deposition, the hallmark characteristics of metabolic disease.
      We demonstrate that during chronic high fat feeding in mice, adipogenic
      differentiation is impaired due to the actions of histone deacetylase 9 (HDAC9),
      a member of the class II family of HDACs. Mechanistically, upregulated HDAC9
      expression blocks the adipogenic differentiation program during chronic high fat
      feeding, leading to accumulation of improperly differentiated adipocytes with
      diminished expression of adiponectin. These adipocytes are inefficient at storing
      lipid, resulting in ectopic lipid deposition in the liver. HDAC9 gene deletion
      prevents the detrimental effects of chronic high fat feeding on adipogenic
      differentiation, increases adiponectin expression, and enhances energy
      expenditure by promoting beige adipogenesis, thus leading to reduced body mass
      and improved metabolic homeostasis. HDAC9 is therefore emerging as a critical
      regulator of adipose tissue health and a novel therapeutic target for obesity
      related disease. 

PMID- 26317060
TI  - ?
AB  - This paper discusses the transformations undergone by Mexican families in the
      20th century and how some internal dynamics unfolded with the increase in the
      individual life expectancy and the presence of functional incapacities in the
      older family members. It reflects on social and demographic changes in the
      families and on support and care strategies directed at elderly people who are
      ill and have functional limitations, based on calculations obtained from the
      Encuesta Nacional sobre Salud y Envejecimiento (2001). Although there are efforts
      on the part of health institutions and family arrangements to deal with this
      situation, this paper shows the strength and the weakness of the social
      protection systems regarding care and support for aged people with functional
      incapacity. It presents challenges and relevant action areas for public and non
      public institutions. It proposes, based on this analysis, that institutions,
      families and the society should take active actions to support the elderly
      individual who undergoes the progressive deterioration of physical and mental
      faculties.

PMID- 26317061
TI  - The Future of Research Communication.
AB  - This report documents the program and the outcomes of Dagstuhl Perspectives
      Workshop 11331 "The Future of Research Communication". The purpose of the
      workshop was to bring together researchers from these different disciplines,
      whose core research goal is changing the formats, standards, and means by which
      we communicate science.

PMID- 26317062
TI  - Clinical Outcome and Mechanisms of Deep Brain Stimulation for Obsessive
      Compulsive Disorder.
AB  - Clinical outcome of deep brain stimulation (DBS) for obsessive-compulsive
      disorder (OCD) shows robust effects in terms of a mean Yale-Brown Obsessive
      Compulsive Scale (YBOCS) reduction of 47.7 % and a mean response percentage
      (minimum 35 % YBOCS reduction) of 58.2 %. It appears that most patients regain a
      normal quality of life (QoL) after DBS. Reviewing the literature of the last 4
      years, we argue that the mechanisms of action of DBS are a combination of
      excitatory and inhibitory as well as local and distal effects. Evidence from DBS
      animal models converges with human DBS EEG and imaging findings, in that DBS may
      be effective for OCD by reduction of hyperconnectivity between frontal and
      striatal areas. This is achieved through reduction of top-down-directed synchrony
      and reduction of frontal low-frequency oscillations. DBS appears to counteract
      striatal dysfunction through an increase in striatal dopamine and through
      improvement of reward processing. DBS affects anxiety levels through reduction of
      stress hormones and improvement of fear extinction.

PMID- 26317063
TI  - Improving Recognition of Children Affected by Prenatal Alcohol Exposure:
      Detection of Exposure in Pediatric Care.
AB  - Early identification of fetal alcohol spectrum disorders (FASDs) is important for
      providing services and preventing secondary disabilities. Recent studies indicate
      that many FASDs are undiagnosed, partly because there is a need to improve
      detection of prenatal alcohol exposure (PAE). The aims of this review are to
      characterize existing practices for assessing PAE in pediatric care, identify the
      most efficient, promising methods of detecting PAE, and recognize the knowledge
      and practice gaps. This review indicates that maternal self-reports remain the
      most common method utilized in routine clinical practice and highlights promising
      methods of PAE identification, including a single binge drinking question. The
      review yields few studies describing existing strategies to assess PAE in
      pediatric practice and identifies knowledge gaps that need to be addressed for
      improving recognition of FASDs in pediatric practice.

PMID- 26317064
TI  - Application of Optical Coherence Tomography (OCT) for Diagnosis of Caries,
      Cracks, and Defects of Restorations.
AB  - Optical coherence tomography (OCT) is a noninvasive technique providing cross
      sectional images of a tooth structure. This review describes the use of OCT for
      detecting dental caries, tooth fractures, and interfacial gaps in intraoral
      restorations. OCT can be a reliable and an accurate method and a safer
      alternative to X-ray radiography.

PMID- 26317065
TI  - Detecting Short-Term Changes in the Activity of Caries Lesions with the Aid of
      New Technologies.
AB  - This paper discusses the use of new technologies for the assessment of caries and
      more in particular changes in caries activity. Over the past decades, we have
      seen a shift from restorative treatment caries to a prevention-driven approach.
      Also there is a need for shorter and less expensive caries clinical trials. These
      demand earlier detection of lesions and the monitoring of lesion changes
      longitudinally in time, which has led to the development of new technologies to
      aid clinical visual examination. Also clinical visual inspection indices have
      been refined to fit this purpose. There is a constant flow of technologies
      emerging and disappearing. This review discusses the merits of recent
      developments regarding their respective uses for research purposes in testing new
      caries prevention strategies as well as in clinical caries management in dental
      private practice. Which technique to choose highly depends on the needed
      resolution of information.

PMID- 26317067
TI  - Type and Frequency of Opioid Pain Medications Returned for Disposal.
AB  - Prescription opioids have increasingly been involved in overdose deaths and
      treatment admissions. Disposal programs may play an important role in curbing
      this trend. The objectives of this study were to: (1) quantify the prescription
      opioids returned for disposal to a local take-back program, and (2) explore
      selected drug characteristics that may predict the quantity of unused opioids.
      Leftover prescription opioid medications returned for disposal to a community
      drug take-back event were quantified and analyzed according to controlled
      substances schedule, formulation, number of active ingredients, and directions
      for use. Days' supply of medication remaining, calculated using the number of
      dosage units remaining divided by the maximum number of dosage units per day
      allowed by the prescriber, was the primary outcome variable. Opioid prescriptions
      returned for disposal had greater than 60 % of the amount dispensed remaining
      unused. Short-acting C-II and C-III combination opioids accounted for greater
      than 80 % of the prescriptions returned. Day supply dispensed was the strongest
      predictor of day supply remaining, regardless of other drug characteristics.
      These findings indicate that disposal programs are effective at removing unused
      medication from patient homes. To reduce leftover medication, prescriber
      education programs should address the amount to be prescribed. Continual
      monitoring of quantities prescribed and returned for disposal may be useful in
      evaluating the effects of these programs on leftover medication. Further research
      on drug characteristics may inform prescribing practices and reduce leftover
      medication.

PMID- 26317066
TI  - New Tools in Experimental Cellular Therapy for the Treatment of Liver Diseases.
AB  - The current standard of care for end stage liver disease is orthotopic liver
      transplantation (OLT). Through improvement in surgical techniques,
      immunosuppression, and general medical care, liver transplantation has become an
      effective treatment over the course of the last half-century. Unfortunately, due
      to the limited availability of donor organs, there is a finite limit to the
      number of patients who will benefit from this therapy. This review will discuss
      current research in experimental cellular therapies for acute, chronic, and
      metabolic liver failure that may be appropriate when liver transplantation is not
      an immediate option.

PMID- 26317068
TI  - First Pregnancy Characteristics, Postmenopausal Breast Density, and Salivary Sex
      Hormone Levels in a Population at High Risk for Breast Cancer.
AB  - BACKGROUND: It remains unknown if later life breast cancer risk as determined by
      reproductive history is mediated by postmenopausal breast density and/or sex
      steroid levels. METHODS: Increased breast density is a strong surrogate for
      future breast cancer risk. A cross-sectional study with a longitudinal follow up
      for breast health outcomes evaluated women without breast cancer (n = 1,023; 682
      = parous), drawn from a high risk postmenopausal population, with questionnaire
      reported reproductive histories. The questionnaire was linked to prospective
      screening mammogram breast density measurements, and saliva biospecimens that
      were used to assess sex steroid hormone levels. RESULTS: Expected age and
      postmenopause related declines in salivary estradiol (E), progesterone (P),
      dehydroepiandrosterone (DHEA) and testosterone (T) levels were observed. This was
      most pronounced for DHEA and T, which were also the only postmenopausal hormone
      levels significantly associated with any reproductive characteristics: parity and
      breast feeding for DHEA, age-at-first birth for T. Postmenopausal breast density
      was borderline significantly lower with parity and higher body mass index (BMI).
      After multivariate analysis, T was the only hormone level to retain any
      association (negative, p<0.05) with breast density. CONCLUSIONS AND GENERAL
      SIGNIFICANCE: While reproductive characteristics, in particular parity, generally
      demonstrated independent associations with postmenopausal breast density and E, P
      and DHEA levels, T levels showed concordant inverse associations with age-at
      first birth and breast density. These findings suggest that reproductive effects
      and later life salivary sex steroid hormone levels may have independent effects
      on later life breast density and cancer risk.

PMID- 26317070
TI  - Era of pharmacovigilance: Revolution in healthcare.

PMID- 26317071
TI  - Application of quality by design approach to optimize process and formulation
      parameters of rizatriptan loaded chitosan nanoparticles.
AB  - The purpose of present study was to optimize rizatriptan (RZT) chitosan (CS)
      nanoparticles using ionic gelation method by application of quality by design
      (QbD) approach. Based on risk assessment, effect of three variables, that is CS
      %, tripolyphosphate % and stirring speed were studied on critical quality
      attributes (CQAs); particle size and entrapment efficiency. Central composite
      design (CCD) was implemented for design of experimentation with 20 runs. RZT CS
      nanoparticles were characterized for particle size, polydispersity index,
      entrapment efficiency, in-vitro release study, differential scanning
      calorimetric, X-ray diffraction, scanning electron microscopy (SEM). Based on QbD
      approach, design space (DS) was optimized with a combination of selected
      variables with entrapment efficiency > 50% w/w and a particle size between 400
      and 600 nm. Validation of model was performed with 3 representative formulations
      from DS for which standard error of - 0.70-3.29 was observed between experimental
      and predicted values. In-vitro drug release followed initial burst release 20.26
      +/- 2.34% in 3-4 h with sustained drug release of 98.43 +/- 2.45% in 60 h. Lower
      magnitude of standard error for CQAs confirms the validation of selected CCD
      model for optimization of RZT CS nanoparticles. In-vitro drug release followed
      dual mechanism via, diffusion and polymer erosion. RZT CS nanoparticles were
      prepared successfully using QbD approach with the understanding of the high risk
      process and formulation parameters involved and optimized DS with a
      multifactorial combination of critical parameters to obtain predetermined RZT
      loaded CS nanoparticle specifications. 

PMID- 26317072
TI  - Pharmacognostic evaluation with reference to catechin content and antioxidant
      activities of pale catechu in Thailand.
AB  - Pale catechu, a well-known crude drug, has been widely used for anti-diarrhea.
      Due to its medicinal usage, this study was performed to evaluate the
      pharmacognostic and antioxidant properties as well as catechins contents of pale
      catechu in Thailand. Twenty samples of pale catechu collected from traditional
      drug stores throughout Thailand were investigated. Antioxidant activities, total
      phenolic, nontannin phenolic, and total tannin contents were evaluated. (+)
      catechin and (-)-epicatechin were quantitatively analyzed by high performance
      liquid chromatography. The results revealed that most of pale catechu samples
      were adulterated according to high ash values. Qualified pale catechu in Thailand
      were demonstrated for their average contents of total ash, acid insoluble ash,
      loss on drying, and moisture as 5.20 +/- 0.19, 1.61 +/- 0.17, 13.14 +/- 0.10, and
      13.20 +/- 1.07 g/100 g of dry weight, respectively. The ethanol and water soluble
      extractive matters were 91.66 +/- 5.16 and 44.59 +/- 3.18 g/100 g of dry weight
      respectively. (+)-catechin in theses samples was 478.87 +/- 2.77 MUg/mg of crude
      drug, whereas (-)-epicatechin was found to be trace (<limit of quantitation). The
      promising antioxidant activities were demonstrated compared to (+)-catechin
      hydrate. 

PMID- 26317069
TI  - S-Nitrosylation in Organs of Mice Exposed to Low or High Doses of gamma-Rays: The
      Modulating Effect of Iodine Contrast Agent at a Low Radiation Dose.
AB  - The covalent addition of nitric oxide (NO*) onto cysteine thiols, or S
      nitrosylation, modulates the activity of key signaling proteins. The
      dysregulation of normal S-nitrosylation contributes to degenerative conditions
      and to cancer. To gain insight into the biochemical changes induced by low-dose
      ionizing radiation, we determined global S-nitrosylation by the "biotin switch"
      assay coupled with mass spectrometry analyses in organs of C57BL/6J mice exposed
      to acute 0.1 Gy of 137Cs gamma-rays. The dose of radiation was delivered to the
      whole body in the presence or absence of iopamidol, an iodinated contrast agent
      used during radiological examinations. To investigate whether similar or distinct
      nitrosylation patterns are induced following high-dose irradiation, mice were
      exposed in parallel to acute 4 Gy of 137Cs gamma rays. Analysis of modulated S
      nitrosothiols (SNO-proteins) in freshly-harvested organs of animals sacrificed 13
      days after irradiation revealed radiation dose- and contrast agent-dependent
      changes. The major results were as follows: (i) iopamidol alone had significant
      effects on S-nitrosylation in brain, lung and liver; (ii) relative to the
      control, exposure to 0.1 Gy without iopamidol resulted in statistically
      significant SNO changes in proteins that differ in molecular weight in liver,
      lung, brain and blood plasma; (iii) iopamidol enhanced the decrease in S
      nitrosylation induced by 0.1 Gy in brain; (iv) whereas a decrease in S
      nitrosylation occurred at 0.1 Gy for proteins of ~50 kDa in brain and for
      proteins of ~37 kDa in liver, an increase was detected at 4 Gy in both organs;
      (v) mass spectrometry analyses of nitrosylated proteins in brain revealed
      differential modulation of SNO proteins (e.g., sodium/potassium-transporting
      ATPase subunit beta-1; beta tubulins; ADP-ribosylation factor 5) by low- and high
      dose irradiation; and (vi) ingenuity pathway analysis identified major signaling
      networks to be modulated, in particular the neuronal nitric oxide synthase
      signaling pathway was differentially modulated by low- and high-dose gamma
      irradiation.

PMID- 26317073
TI  - Evaluation of wound healing activity of Thunbergia laurifolia supercritical
      carbon dioxide extract in rats with second-degree burn wounds.
AB  - Thunbergia laurifolia Lindl (TL) has been traditionally used as an antidote, anti
      inflammatory, and anti-drug addiction. This study investigated the burn wound
      healing activity of TL leaf extract (TLL) from supercritical CO2 extraction in
      rats. The extract was prepared to 2.5%, 5%, and 10% gel (TLL gel). Rats were
      induced to second-degree burn wounds. They were randomly divided into six groups
      (six rats/group), which five groups were topically applied gel base, 1% silver
      sulfadiazine gel, 2.5%, 5%, and 10% TLL gel, respectively, for 14 days. Six
      untreated burn rats were used as the control group. The rats in each group were
      evaluated for wound healing rate, histological parameters, and wound collagen
      content. Rats treated with 10% TLL gel had a higher wound healing rate than rats
      in the control and untreated groups. An increase in collagen content, which
      indicates good regeneration of wound skin, was observed in the TLL treated rats
      from a pathological study by Masson's trichrome and collagen content assay. The
      results from this study suggest that T. laurifolia leaf extract obtained by
      supercritical CO2 extraction promotes the recovery of wound skin by shortening
      the inflammation phase, increasing collagen content, and stimulating fibroblasts
      proliferation and migration in wound healing. 

PMID- 26317074
TI  - A reverse phased high-pressure liquid chromatographic method for the estimation
      of a poisonous matter in Strychnos nux-vomica.
AB  - Seeds of Strychnos nux-vomica were subjected to preliminary phytochemical tests
      and its presence was confirmed by thin layer chromatography (TLC) method. The TLC
      profile of the methanolic extract of seeds of S. nux-vomica was developed using
      the solvent system toluene:chloroform:methanol in the ratio 8:2:1. The plate was
      observed in visible light after spraying with Dragendorff's reagent (specific
      method). High-performance liquid chromatography (HPLC) profile of the methanolic
      extracts of S. nux-vomica was developed, and the amount of strychnine seems to be
      0.36% (w/w) in the seeds. The TLC and HPLC profiles developed are very valuable
      for the identification of the original drug from their adulterants. The TLC
      profile identifies the presence of strychnine in the plant material. The
      quantification method for the strychnine in the seeds can be used for the quality
      standardization of the raw drug because the strychnine is reported to have some
      toxicity. 

PMID- 26317075
TI  - Chalcone derivatives as potential antifungal agents: Synthesis, and antifungal
      activity.
AB  - Much research has been carried out with the aim to discover the therapeutic
      values of chalcone derivatives. Chalcones possess wide range of pharmacological
      activity such as antibacterial, antimalarial, antiprotozoal, antitubercular,
      anticancer, and antifungal agents etc. The presence of reactive alpha,beta
      unsaturated keto group in chalcones is found to be responsible for their
      biological activity. The rapid developments of resistance to antifungal agents,
      led to design, and synthesize the new antifungal agents. The derivatives of
      chalcones were prepared using Claisen-Schmidt condensation scheme with
      appropriate tetralone and aldehyde derivatives. Ten derivatives were synthesized
      and were biologically screened for antifungal activity. The newly synthesized
      derivatives of chalcone showed antifungal activity against fungal species,
      Microsporum gypseum. The results so obtained were superior or comparable to
      ketoconazole. It was observed that none of the compounds tested showed positive
      results for fungi Candida albicans nor against fungi Aspergillus niger. Chalcone
      derivatives showed inhibitory effect against M. gypseum species of fungus. It was
      found that among the chalcone derivatives so synthesized, two of them, that is, 4
      chloro derivative, and unsubstituted derivative of chalcone showed antifungal
      activity superior to ketoconazole. Thus, these can be the potential new molecule
      as antifungal agent. 

PMID- 26317076
TI  - Development, validation of liquid chromatography-tandem mass spectrometry method
      for simultaneous determination of rosuvastatin and metformin in human plasma and
      its application to a pharmacokinetic study.
AB  - A new, simple and accurate liquid chromatography-tandem mass spectrometry (LC
      MS/MS) method for simultaneous determination of rosuvastatin (ROS) and metformin
      (MET) in human plasma was developed. The assay procedure involved simple protein
      precipitation with acetonitrile. Following precipitation, fraction of supernatant
      was decanted and evaporated under gentle stream of nitrogen at 40 degrees C. The
      residue was reconstituted in mobile phase and injected. The chromatographic
      separation was achieved with Thermo Hypurity C18 column (50 mm * 4.6 mm, 5 MU)
      using a mobile phase composition containing 0.1% v/v formic acid in water and
      acetonitrile (30:70, v/v) at a flow rate of 0.4 mL/min. The total run time was
      3.5 min. The method showed good linearity in the range 0.5-200 ng/mL for ROS and
      2-2000 ng/mL for MET with correlation coefficient (r) >0.9994 for both the
      analytes. The intra and inter-day precision values for ROS and MET met the
      acceptance criteria as per regulatory guidelines. The battery of stability
      studies viz., bench-top, freeze-thaw and long term stability were performed. The
      developed method was applied to a pharmacokinetic study. 

PMID- 26317077
TI  - In-silico study of small cell lung cancer based on protein structure and
      function: A new approach to mimic biological system.
AB  - Lung cancer being the most common disease worldwide that leads to a number of
      deaths. A huge amount of effort has been done in screening trials for early
      diagnose treatment which increases the disease-free survival rate. Based on the
      expression of protein of mouse double minute 2 and tumor protein 53 complex, we
      have identified the antagonist for this complex that would facilitate the
      treatment for specific lung cancer. It is a complex disease that involves vast
      investigation for the characterization of a lung cancer and thus, computational
      study is being developed to mimic the in vivo system. In this work, a
      computational process was employed for the identification of these proteins, with
      a short and simple method to discover protein-protein interactions. Moreover,
      these proteins have more similarities in their function with the known cancer
      proteins as compared to those identified from the protein expression specific
      profiles. A new method that utilizes experimental information to improve the
      extent of numerical calculations based on free energy profiles from molecular
      dynamics simulation. The experimental information guides the simulation along
      relevant pathways and decreases overall computational time. This method
      introduces umbrella sampling simulations. A new technique umbrella sampling is
      described where the high efficacy100 of this technique enables uniform sampling
      with several degrees of freedom. Here, we review the protein interactions
      techniques and we focus on main concepts in the molecular of in-silico study in
      lung cancer. This study recruiting new methods proved the efficiency and showed
      good results. 

PMID- 26317078
TI  - A comparative study of neuroprotective effect of angiotensin converting enzyme
      inhibitors against scopolamine-induced memory impairments in rats.
AB  - The comparative study of neuroprotective effect of angiotensin converting enzyme
      inhibitors against scopolamine-induced neuroinflammation in albino Wistar rats
      was studied. Male albino rats were administered with scopolamine to induce memory
      impairment. The standard nootropic agent, piracetam (200 mg/kg b.w., [i.p.]),
      perindopril (0.1 mg/kg b.w., [i.p.]), enalapril (0.1 mg/kg b.w., [i.p.]), and
      ramipril (0.1 mg/kg b.w., [i.p.]) were administered in different group of animals
      for 5 days. On 5(th) day, scopolamine (1 mg/kg b.w., i.p.) was administered after
      60 min of the last dose of test drug. Memory function was evaluated in Morris
      water maze (MWM) test and pole climbing test (PCT). Biochemical estimations like
      glutathione (GSH), malondialdehyde (MDA), and acetylcholinesterase activity in
      the brain were estimated after completion of behavior study. All three test
      groups shows improvement in learning and memory in comparison to control group.
      Perindopril treated group showed a more effective significant decrease in escape
      latency time and transfer latency time compared to enalapril and ramipril treated
      group on day 4 in MWM test and PCT, respectively. Perindopril shows a significant
      reduction in MDA level and acetylcholinesterase activity and a significant rise
      in GSH level compared to enalapril and ramipril. The finding of this study
      indicates that Perindopril is more effective in memory retention compared to
      enalapril and ramipril. 

PMID- 26317079
TI  - Comparison of the efficacy of cardamom (Elettaria cardamomum) with pioglitazone
      on dexamethasone-induced hepatic steatosis, dyslipidemia, and hyperglycemia in
      albino rats.
AB  - To evaluate the efficacy of cardamom with pioglitazone on dexamethasone-induced
      hepatic steatosis, dyslipidemia, and hyperglycemia in albino rats. There were
      four groups of 6 rats each. First group received dexamethasone alone in a dose of
      8 mg/kg intraperitoneally for 6 days to induce metabolic changes and considered
      as dexamethasone control. Second group received cardamom suspension 1 g/kg/10 mL
      of 2% gum acacia orally 6 days before dexamethasone and 6 days during
      dexamethasone administration. Third group received pioglitazone 45 mg/kg orally 6
      days before dexamethasone and 6 days during dexamethasone administration. Fourth
      group did not receive any medication and was considered as normal control.
      Fasting blood sugar, lipid profile, blood sugar 2 h after glucose load, liver
      weight, liver volume were recorded, and histopathological analysis was done. The
      effects of cardamom were compared with that of pioglitazone. Dexamethasone caused
      hepatomegaly, dyslipidemia and hyperglycemia. Both pioglitazone and cardamom
      significantly reduced hepatomegaly, dyslipidemia, and hyperglycemia (P < 0.01).
      Reduction of blood sugar levels after glucose load was significant with
      pioglitazone in comparison to cardamom (P < 0.01). Cardamom has comparable
      efficacy to pioglitazone in preventing dexamethasone-induced hepatomegaly,
      dyslipidemia, and fasting hyperglycemia. 

PMID- 26317080
TI  - Synthesis, antifungal and antibacterial activity of novel 1,2,4-triazole
      derivatives.
AB  - A large number of 1,2,4-triazole-containing ring system have been incorporated
      into a wide variety of therapeutically interesting drug candidates including anti
      inflammatory, central nervous system stimulants, antianxiety, and antimicrobial
      agents. To overcome the rapid development of drug resistance, new agents should
      preferably have chemical characteristics that clearly differ from those of
      existing agents. Thus led to the design and synthesize the new antimicrobial
      agents. A novel series of Schiff bases based on of 4-(benzylideneamino)-5-phenyl
      4H-1,2,4-triazole-3-thiol scaffold was prepared by heating thiocarbohydrazide and
      substituted benzoic acid and subsequently, treating with substituted
      benzaldehydes. Seventeen derivatives were synthesized and were biologically
      screened for antifungal and antibacterial activity. The newly synthesized
      derivatives of triazole showed antifungal activity against fungal species,
      Microsporum gypseum; and antibacterial activity against bacterial species,
      Staphylococcus aureus. It was observed that none of the compounds tested showed
      positive results for fungi Candida albicans fungi Aspergillus niger, nor against
      bacterial strain Escherichia coli. Strong antifungal effects were obtained for
      the synthesized compounds against M. gypseum and were superior or comparable to
      standard drug ketoconazole. Similarly, all of the synthesized compounds exhibit
      strong antibacterial activity against S. aureus and were superior or comparable
      to standard drug streptomycin. It was found that among the triazole derivatives
      so synthesized, six of them, showed antifungal activity superior to ketoconazole
      while one of them, showed antibacterial activity superior to streptomycin. Thus,
      these can be the potential new molecule as an antimicrobial agent. 

PMID- 26317081
TI  - Formation of a vesicovaginal fistula in a pig model.
AB  - OBJECTIVE: To establish an animal model of a vesicovaginal fistula that can later
      be used in the development of new treatment modalities. MATERIALS AND METHODS:
      Six female pigs of Landrace/Yorkshire breed were used. Vesicotomy was performed
      through open surgery. An standardized incision between the bladder and the vagina
      was made, and the mucosa between them was sutured together with absorbable
      sutures. A durometer ureteral stent was introduced into the fistula, secured with
      sutures to the bladder wall, allowing for the formation of a persistent fistula
      tract. Six weeks postoperatively cystoscopy was performed to examine the fistula
      in vivo. Thereafter, the pigs were euthanized with intravenous pentobarbital.
      RESULTS: Two out of four (50%) pigs developed persistent fistulas. No per- or
      postoperative complications occurred. CONCLUSION: This study indicates that this
      pig model of vesicovaginal fistula can be an effective and cheap way to create a
      fistula between the bladder and vagina.

PMID- 26317082
TI  - Verification of relationships between anthropometric variables among ureteral
      stents recipients and ureteric lengths: a challenge for Vitruvian-da Vinci
      theory.
AB  - OBJECTIVE: To determine and verify how anthropometric variables correlate to
      ureteric lengths and how well statistical models approximate the actual ureteric
      lengths. MATERIALS AND METHODS: In this work, 129 charts of endourological
      patients (71 females and 58 males) were studied retrospectively. Data were
      gathered from various research centers from North and South America. Continuous
      data were studied using descriptive statistics. Anthropometric variables (age,
      body surface area, body weight, obesity, and stature) were utilized as predictors
      of ureteric lengths. Linear regressions and correlations were used for studying
      relationships between the predictors and the outcome variables (ureteric
      lengths); P-value was set at 0.05. To assess how well statistical models were
      capable of predicting the actual ureteric lengths, percentages (or ratios of
      matched to mismatched results) were employed. RESULTS: The results of the study
      show that anthropometric variables do not correlate well to ureteric lengths.
      Statistical models can partially estimate ureteric lengths. Out of the five
      anthropometric variables studied, three of them: body frame, stature, and weight,
      each with a P<0.0001, were significant. Two of the variables: age (R (2)=0.01;
      P=0.20) and obesity (R (2)=0.03; P=0.06), were found to be poor estimators of
      ureteric lengths. None of the predictors reached the expected (match:above:below)
      ratio of 1:0:0 to qualify as reliable predictors of ureteric lengths. CONCLUSION:
      There is not sufficient evidence to conclude that anthropometric variables can
      reliably predict ureteric lengths. These variables appear to lack adequate
      specificity as they failed to reach the expected (match:above:below) ratio of
      1:0:0. Consequently, selections of ureteral stents continue to remain a
      challenge. However, height (R (2)=0.68) with the (match:above:below) ratio of
      3:3:4 appears suited for use as estimator, but on the basis of decision rule.
      Additional research is recommended for stent improvements and ureteric length
      determinations.

PMID- 26317084
TI  - The quantitative sensory testing is an efficient objective method for assessment
      of nerve injury.
AB  - BACKGROUND: This study evaluated Somatosensory evoked potentials (SEP),
      Quantitative sensory testing (QST), and thermography as diagnostic methods for
      nerve injury. METHODS: From 2006 through 2011, 17 patients (mean age: 50.1 years)
      from OOOO Hospital who sought care for altered sensation after dental implant
      treatment were identified. The mean time of objective assessment was 15.2 months
      after onset. RESULTS: SEP of Inferior alveolar nerve(IAN) was 15.87 +/- 0.87 ms
      on the normal side and 16.18 +/- 0.73 ms on the abnormal side. There was delayed
      N20 latency on the abnormal side, but the difference was not statistically
      significant. In QST, the abnormal side showed significantly higher scores of the
      current perception threshold at 2 KHz, 250 Hz, and 5 Hz. The absolute temperature
      difference was 0.55 degrees C without statistically significance. CONCLUSION:
      These results indicate that QST is valuable as an objective method for assessment
      of nerve injury.

PMID- 26317083
TI  - Minimally invasive devices for treating lower urinary tract symptoms in benign
      prostate hyperplasia: technology update.
AB  - Benign prostatic hyperplasia (BPH) represents a spectrum of related lower urinary
      tract symptoms (LUTS). The cost of currently recommended medications and the
      discontinuation rate due to side effects are significant drawbacks limiting their
      long-term use in clinical practice. Interventional procedures, considered as the
      definitive treatment for BPH, carry a significant risk of treatment-related
      complications in frail patients. These issues have contributed to the emergence
      of new approaches as alternative options to standard therapies. This paper
      reviews the recent literature regarding the experimental treatments under
      investigation and presents the currently available experimental devices and
      techniques used under local anesthesia for the treatment of LUTS/BPH in the vast
      majority of cases. Devices for delivery of thermal treatment (microwaves,
      radiofrequency, high-intensity focused ultrasound, and the Rezum system),
      mechanical devices (prostatic stent and urethral lift), fractionation of
      prostatic tissue (histotripsy and aquablation), prostate artery embolization, and
      intraprostatic drugs are discussed. Evidence for the safety, tolerability, and
      efficacy of these "minimally invasive procedures" is analyzed. 

PMID- 26317085
TI  - Encoding into Visual Working Memory: Event-Related Brain Potentials Reflect
      Automatic Processing of Seemingly Redundant Information.
AB  - Encoding and maintenance of information in visual working memory in an S1-S2 task
      with a 1500 ms retention phase were investigated by means of event-related brain
      potentials (ERPs). Participants were asked to decide whether two visual stimuli
      were physically identical (identity comparison (IC) task) or belonged to the same
      set or category of equivalent patterns (category comparison (CC) task). The
      stimuli differ with regard to two features. (1) Each pattern can belong to a set
      of either four (ESS 4) or eight (ESS 8) equivalent patterns, mirroring
      differences in the complexity with regard to the representational structure of
      each pattern (i.e., equivalence set size (ESS)). (2) The set of patterns differ
      with regard to the rated complexity. Memory performance obtained the effects of
      the task instructions (IC versus CC) and the ESS (ESS 4 versus ESS 8) but not of
      the rated complexity. ERPs in the retention interval reveal that the stimulus
      related factors (subjective complexity and ESS) affect the encoding of the
      stimuli as mirrored by the pronounced P3b amplitude in ESS 8 compared to ESS 4
      patterns. Importantly, these effects are independent of task instructions. The
      pattern of results suggests an automatic processing of the ESS in the encoding
      phase. 

PMID- 26317086
TI  - The Modulation of Error Processing in the Medial Frontal Cortex by Transcranial
      Direct Current Stimulation.
AB  - Background. In order to prevent future errors, we constantly control our behavior
      for discrepancies between the expected (i.e., intended) and the real action
      outcome and continuously adjust our behavior accordingly. Neurophysiological
      correlates of this action-monitoring process can be studied with event-related
      potentials (error-related negativity (ERN) and error positivity (Pe)) originating
      from the medial prefrontal cortex (mPFC). Patients with neuropsychiatric diseases
      often show performance monitoring dysfunctions potentially caused by pathological
      changes of cortical excitability; therefore, a modulation of the underlying
      neuronal activity might be a valuable therapeutic tool. One technique which
      allows us to explore cortical modulation of neural networks is transcranial
      direct current stimulation (tDCS). Therefore, we tested the effect of medial
      prefrontal tDCS on error-monitoring potentials in 48 healthy subjects randomly
      assigned to anodal, cathodal, or sham stimulation. Results. We found that
      cathodal stimulation attenuated Pe amplitudes compared to both anodal and sham
      stimulation, but no effect for the ERN. Conclusions. Our results indicate that
      cathodal tDCS over the mPFC results in an attenuated cortical excitability
      leading to decreased Pe amplitudes. We therefore conclude that tDCS has a
      neuromodulatory effect on error-monitoring systems suggesting a future approach
      to modify the sensitivity of corresponding neural networks in patients with
      action-monitoring deficits. 

PMID- 26317087
TI  - Brain SERT Expression of Male Rats Is Reduced by Aging and Increased by
      Testosterone Restitution.
AB  - In preclinical and clinical studies aging has been associated with a deteriorated
      response to antidepressant treatment. We hypothesize that such impairment is
      explained by an age-related decrease in brain serotonin transporter (SERT)
      expression associated with low testosterone (T) levels. The objectives of this
      study were to establish (1) if brain SERT expression is reduced by aging and (2)
      if the SERT expression in middle-aged rats is increased by T-restitution. Intact
      young rats (3-5 months) and gonad-intact middle-aged rats with or without T
      restitution were used. The identification of the brain SERT expression was done
      by immunofluorescence in prefrontal cortex, lateral septum, hippocampus, and
      raphe nuclei. An age-dependent reduction of SERT expression was observed in all
      brain regions examined, while T-restitution recovered the SERT expression only in
      the dorsal raphe of middle-aged rats. This last action seems relevant since
      dorsal raphe plays an important role in the antidepressant action of selective
      serotonin reuptake inhibitors. All data suggest that this mechanism accounts for
      the T-replacement usefulness to improve the response to antidepressants in the
      aged population. 

PMID- 26317088
TI  - Circadian Levels of Serum Melatonin and Cortisol in relation to Changes in Mood,
      Sleep, and Neurocognitive Performance, Spanning a Year of Residence in
      Antarctica.
AB  - Background. Altered circadian cortisol and melatonin rhythms in healthy subjects
      exposed to an extreme polar photoperiod results in changes in mood and sleep,
      which can influence cognitive performance. Materials and Methods. We assessed the
      circadian rhythm of 20 subjects who wintered over at Maitri (70 degrees S, 11
      degrees E), India's permanent Antarctic station, from November 2010 to December
      2011. Serum cortisol and melatonin levels were measured by radioimmunoassay at 8
      am, 3 pm, 8 pm, and 2 am in a single day, once each during the polar summer and
      winter photoperiods. Conventional psychological tests, Depression, Anxiety, and
      Stress Scale (DASS-42), Epworth Sleepiness Scale (ESS), and a computerized
      neurocognitive test battery were used to measure mood, sleep, and cognitive
      performance. Results. The mean scores for DASS42 were higher during midwinter
      suggesting the presence of "overwintering." Mean diurnal cortisol levels during
      summer and winter were comparable, but the levels of melatonin were markedly
      higher during winter. Higher 8 am melatonin levels were associated with better
      sleep quality, lower depression scores, and better performance in tasks like
      attention, visual memory, and arithmetic. Conclusion. Timing of artificial light
      exposure and usage of melatonin supplements in improving sleep and cognitive
      performance in expedition teams are of future research interest. 

PMID- 26317089
TI  - Functional Outcomes of Surgery in Cervical Spondylotic Radiculopathy versus
      Myelopathy: A Comparative Study.
AB  - Background. Cervical spondylosis can cause three different categories of symptoms
      and signs with possible overlap in the affected patients. Aim. We aim to compare
      functional outcome of surgery in the patients with cervical spondylotic
      radiculopathy and myelopathy, regardless of their surgical type and approach.
      Materials and Methods. We retrospectively reviewed 140 patients with cervical
      spondylotic radiculopathy and myelopathy who had been operated from August 2006
      to January 2011, as Group A (68 cases) and Group B (72 cases), respectively. The
      mean age was 48.2 and 55.7 years, while the mean followup was 38.9 and 37.3
      months, respectively. Functional outcome of the patients was assessed by neck
      disability index (NDI) and patient satisfaction with surgery. Results. Only in
      Group A, the longer delay caused a worse surgical outcome (NDI). In addition, in
      Group B, there was no significant relationship between imaging signal change of
      the spinal cord and our surgical outcomes. Improvement in NDI and final
      satisfaction rate in both groups are comparable. Conclusions. Surgery was
      associated with an improvement in NDI in both groups (P < 0.001). The functional
      results in both groups were similar and comparable, regarding this index and
      patient's satisfaction score. 

PMID- 26317090
TI  - Cognitive, Affective, and Motivational Changes during Ostracism: An ERP, EMG, and
      EEG Study Using a Computerized Cyberball Task.
AB  - Individuals are known to be highly sensitive to signs of ostracism, such as being
      ignored or excluded; however, the cognitive, affective, and motivational
      processes underlying ostracism have remained unclear. We investigated temporal
      changes in these psychological states resulting from being ostracized by a
      computer. Using event-related brain potentials (ERPs), the facial electromyogram
      (EMG), and electroencephalogram (EEG), we focused on the P3b amplitude,
      corrugator supercilii activity, and frontal EEG asymmetry, which reflect
      attention directed at stimuli, negative affect, and approach/withdrawal
      motivation, respectively. Results of the P3b and corrugator supercilii activity
      replicated findings of previous studies on being ostracized by humans. The mean
      amplitude of the P3b wave decreased, and facial EMG activity increased over time.
      In addition, frontal EEG asymmetry changed from relative left frontal activation,
      suggestive of approach motivation, to relative right frontal activation,
      indicative of withdrawal motivation. These findings suggest that ostracism by a
      computer-generated opponent is an aversive experience that in time changes the
      psychological status of ostracized people, similar to ostracism by human. Our
      findings also imply that frontal EEG asymmetry is a useful index for
      investigating ostracism. Results of this study suggest that ostracism has well
      developed neurobiological foundations. 

PMID- 26317091
TI  - Significance of Visual Evoked Potentials in the Assessment of Visual Field
      Defects in Primary Open-Angle Glaucoma: A Review.
AB  - Visual evoked potentials is an important visual electrophysiological tool which
      has been used for the evaluation of visual field defects in primary open-angle
      glaucoma and is an appropriate objective measure of optic nerve function.
      Significant correlations between the magnitude of the VEP parameters and MD of
      Humphrey static perimetry suggest that the impaired visual cortical responses
      observed in glaucoma patients can be revealed by both electrophysiological and
      psychophysical methods. In addition, the severity of global glaucomatous damage
      evidenced by reduction in MD could depend on the delay in neural conduction from
      retina to the visual cortex as revealed by the significant correlation between
      VEP latencies and MD which also supports the validity of the VEP testing in
      progression of glaucoma. 

PMID- 26317092
TI  - Significance of Haemodynamic and Haemostatic Factors in the Course of Different
      Manifestations of Cerebral Small Vessel Disease: The SHEF-CSVD Study-Study
      Rationale and Protocol.
AB  - Rationale. This paper describes the rationale and design of the SHEF-CSVD Study,
      which aims to determine the long-term clinical and radiological course of
      cerebral small vessel disease (CSVD) and to evaluate haemostatic and haemodynamic
      prognostic factors of the condition. Design. This single-centre, prospective, non
      interventional cohort study will follow 150 consecutive patients with different
      clinical manifestations of CSVD (lacunar ischaemic stroke, vascular dementia,
      vascular parkinsonism or spontaneous deep, intracerebral haemorrhage) and 50 age-
      and sex-matched controls over a period of 24 months. The clinical and
      radiological course will be evaluated basing on a detailed neurological,
      neuropsychological and MRI examinations. Haemodynamic (cerebral vasoreactivity,
      24 h blood pressure control) and haemostatic factors (markers of endothelial and
      platelet dysfunction, brachial artery flow-mediated dilatation test) will be
      determined. Discussion. The scheduled study will specifically address the issue
      of haemodynamic and haemostatic prognostic factors and their course over time in
      various clinical manifestations of CSVD. The findings may aid the development of
      prophylactic strategies and individualised treatment plans, which are critical
      during the early stages of the disease. 

PMID- 26317093
TI  - Incidental Findings in Neuroimaging: Ethical and Medicolegal Considerations.
AB  - With the rapid advances in neurosciences in the last three decades, there has
      been an exponential increase in the use of neuroimaging both in basic sciences
      and clinical research involving human subjects. During routine neuroimaging,
      incidental findings that are not part of the protocol or scope of research agenda
      can occur and they often pose a challenge as to how they should be handled to
      abide by the medicolegal principles of research ethics. This paper reviews the
      issue from various ethical (do no harm, general duty to rescue, and mutual
      benefits and owing) and medicolegal perspectives (legal liability, fiduciary
      duties, Law of Tort, and Law of Contract) with a suggested protocol of approach. 

PMID- 26317094
TI  - Biochemical Evidence for a Putative Inositol 1,3,4,5-Tetrakisphosphate Receptor
      in the Olfactory System of Atlantic Salmon (Salmo salar).
AB  - Olfactory receptor neurons in Atlantic salmon (Salmo salar) appear to use a
      phosphoinositide-directed phospholipase C (PLC) in odorant signal transduction.
      The consequences of odor-activated PLC depend on its product, inositol 1,4,5
      trisphosphate (IP3). Therefore, a plasma membrane rich (PMR) fraction, previously
      characterized from salmon olfactory rosettes, was used to study binding sites for
      IP3 and its phosphorylation product, inositol 1,3,4,5-tetrakisphosphate (IP4).
      Binding sites for IP3 were present at the lower limit for detection in the PMR
      fraction but were abundant in a microsomal fraction. Binding sites for IP4 were
      abundant in the PMR fraction and thus colocalized in the same subcellular
      fraction with odorant receptors for amino acids and bile acids. Binding of IP4
      was saturable and high affinity (K d  = 83 nM). The rank order for potency of
      inhibition of IP4 by other inositol polyphosphates (InsP x ) followed the
      phosphorylation number with InsP6 > InsP5 > other InsP4 isomers > InsP3 isomers >
      InsP2 isomers, with the latter showing no activity. The consequences of PLC
      activity in this system may be dictated in part by a putative receptor for IP4. 

PMID- 26317095
TI  - Detecting Silent Vocalizations in a Locked-In Subject.
AB  - Problem Addressed. Decoding of silent vocalization would be enhanced by detecting
      vocalization onset. This is necessary in order to improve decoding of neural
      firings and thus synthesize near conversational speech in locked-in subjects
      implanted with brain computer interfacing devices. Methodology. Cortical
      recordings were obtained during attempts at inner speech in a mute and paralyzed
      subject (ER) implanted with a recording electrode to detect and analyze lower
      beta band peaks meeting the criterion of a minimum 0.2% increase in the power
      spectrum density (PSD). To provide supporting data, three speaking subjects were
      used in a similar testing paradigm using EEG signals recorded over the speech
      area. Results. Conspicuous lower beta band peaks were identified around the time
      of assumed speech onset. The correlations between single unit firings, recorded
      at the same time as the continuous neural signals, were found to increase after
      the lower beta band peaks as compared to before the peaks. Studies in the
      nonparalyzed control individuals suggested that the lower beta band peaks were
      related to the movement of the articulators of speech (tongue, jaw, and lips),
      not to higher order speech processes. Significance and Potential Impact. The
      results indicate that the onset of silent and overt speech is associated with a
      sharp peak in lower beta band activity-an important step in the development of a
      speech prosthesis. This raises the possibility of using these peaks in online
      applications to assist decoding paradigms being developed to decode speech from
      neural signal recordings in mute humans. 

PMID- 26317096
TI  - rTMS as a Treatment of Alzheimer's Disease with and without Comorbidity of
      Depression: A Review.
AB  - With an ever-increasing population of Alzheimer's disease (AD) patients
      worldwide, a noninvasive treatment for AD is needed. In this paper, the
      application of repetitive transcranial magnetic stimulus (rTMS) as a treatment
      for patients with probable AD is compared to the application of rTMS as a
      treatment for depression. Comorbidity of depression and dementia is discussed, as
      well as possible links between the two diseases. The possible confounding
      antidepressant effects of rTMS on cognitive improvements in AD patients are
      discussed. 

PMID- 26317097
TI  - Surgical Outcome of Treating Grades II and III Meningiomas: A Report of 32 Cases.
AB  - Aim. To evaluate the frequency of atypical and malignant meningiomas and analyze
      recurrence rate; to study the morbidity and mortality of these tumors compared to
      benign meningiomas. Methods. During 1992-2007, 16 patients with malignant and 16
      patients with atypical meningioma were operated in Neurosurgery Department of
      Thessaloniki's Papanikolaou Hospital. We analyzed tumor histology, location, and
      extent of surgical resection with respect to tumor reappearance and patients'
      outcome and compared the behavior of benign versus nonbenign meningiomas.
      Results. Malignant meningiomas accounted for 4.4% (16 patients) and atypical
      meningiomas for another 4.4% of the series of patients (353) who were operated
      for intracranial meningioma at our department that period. Malignant meningiomas
      recurred at a rate of 75% and atypical meningiomas recurred at a rate of 41.6%.
      There was a significant association of the histological classification (benign,
      atypical, and malignant) with recurrence (P < 0.01). The recurrence rate after
      complete resection was 13.8%. The recurrence rate for incomplete resection was
      46.7%. Extent of tumor removal was significant to recurrence (P < 0.001) for
      benign as well for atypical and malignant meningiomas. Tumor location (P > 0.05)
      was not significant to recurrence. Conclusions. Atypical and malignant
      meningiomas appeared at a rate of 8.8% of our series of intracranial meningiomas.
      They showed a significant predisposition to recur. These rare subtypes have
      higher morbidity and mortality rates than benign meningiomas. Recurrence depends
      primarily on the extent of surgical removal and on the histological
      characterization of the tumor as atypical or malignant. 

PMID- 26317098
TI  - The mGlu2/3 Receptor Agonists LY354740 and LY379268 Differentially Regulate
      Restraint-Stress-Induced Expression of c-Fos in Rat Cerebral Cortex.
AB  - Metabotropic glutamate 2/3 (mGlu2/3) receptors have emerged as potential
      therapeutic targets due to the ability of mGlu2/3 receptor agonists to modulate
      excitatory transmission at specific synapses. LY354740 and LY379268 are selective
      and potent mGlu2/3 receptor agonists that show both anxiolytic- and antipsychotic
      like effects in animal models. We compared the efficacy of LY354740 and LY379268
      in attenuating restraint-stress-induced expression of the immediate early gene c
      Fos in the rat prelimbic (PrL) and infralimbic (IL) cortex. LY354740 (10 and 30
      mg/kg, i.p.) showed statistically significant and dose-related attenuation of
      stress-induced increase in c-Fos expression, in the rat cortex. By contrast,
      LY379268 had no effect on restraint-stress-induced c-Fos upregulation (0.3-10
      mg/kg, i.p.). Because both compounds inhibit serotonin 2A receptor (5-HT2AR)
      induced c-Fos expression, we hypothesize that LY354740 and LY379268 have
      different in vivo properties and that 5-HT2AR activation and restraint stress
      induce c-Fos through distinct mechanisms. 

PMID- 26317099
TI  - Gene Network Analysis in Amygdala following Taste Aversion Learning in Rats.
AB  - Conditioned taste aversion (CTA) is an adaptive behavior that benefits survival
      of animals including humans and also serves as a powerful model to study the
      neural mechanisms of learning. Memory formation is a necessary component of CTA
      learning and involves neural processing and regulation of gene expression in the
      amygdala. Many studies have been focused on the identification of intracellular
      signaling cascades involved in CTA, but not late responsive genes underlying the
      long-lasting behavioral plasticity. In this study, we explored in silico
      experiments to identify persistent changes in gene expression associated with CTA
      in rats. We used oligonucleotide microarrays to identify 248 genes in the
      amygdala regulated by CTA. Pathway Studio and IPA software analyses showed that
      the differentially expressed genes in the amygdala fall in diverse functional
      categories such as behavior, psychological disorders, nervous system development
      and function, and cell-to-cell signaling. Conditioned taste aversion is a complex
      behavioral trait which involves association of visceral and taste inputs,
      consolidation of taste and visceral information, memory formation, retrieval of
      stored information, and extinction phase. In silico analysis of differentially
      expressed genes is therefore necessary to manipulate specific phase/stage of CTA
      to understand the molecular insight. 

PMID- 26317100
TI  - Age-Induced Loss of Mossy Fibre Synapses on CA3 Thorns in the CA3 Stratum
      Lucidum.
AB  - Advanced ageing is associated with hippocampal deterioration and mild cognitive
      decline. The hippocampal subregion CA3 stratum lucidum (CA3-SL) receives neuronal
      inputs from the giant mossy fibre boutons of the dentate gyrus, but relatively
      little is known about the integrity of this synaptic connection with ageing.
      Using serial electron microscopy and unbiased stereology, we examined age-related
      changes in mossy fibre synapses on CA3 thorny excrescences within the CA3-SL of
      young adults (4-month-old), middle-aged (12-month-old), and old-aged (28-month
      old) Wistar rats. Our data show that while there is an increase in CA3 volume
      with ageing, there is a significant (40-45%) reduction in synaptic density within
      the CA3-SL of 12- and 28-month-old animals compared with 4-month-old animals. We
      also present preliminary data showing that the CA3 neuropil in advanced ageing
      was conspicuously full of lipofuscin and phagolysosome positive, activated
      microglial cellular processes, and altered perivascular pathology. These data
      suggest that synaptic density in the CA3-SL is significantly impaired in ageing,
      accompanied by underlying prominent ultrastructural glial and microvascular
      changes. 

PMID- 26317101
TI  - Association of Metabolic Syndrome and Inflammation with Cognitive Decline in
      Adults Aged 60 Years and Older: Findings from a National Health Survey in the
      United States.
AB  - Objectives. We aimed to test the hypothesis that metabolic syndrome (MetS) is
      significantly associated with cognitive decline (CoD) in elderly adults and
      further assess whether MetS and inflammation have a significant joint effect on
      CoD. Methods. Data (n = 2975) from the U.S. National Health and Nutrition
      Examination Survey (1999-2002) in participants aged >=60 years who had Digit
      Symbol Substitution Tests (DSS: a standard measure of cognitive function) were
      studied. CoD was defined as those in the lowest quintile of DSS score. MetS was
      defined as having >=3 of 5 MetS traits (large waist circumference (WC), high
      blood pressure (BP), elevated glucose, triglycerides, and decreased high density
      lipoprotein cholesterol). Results. Of 2975 participants, the prevalence of CoD
      (DSS score <25) was 12.1%. After adjusting covariates, individual large WC, high
      BP, elevated glucose level, and MetS were significantly associated with CoD in
      logistic regression models (P < 0.001). There was a significant dose-response
      relationship between an increased number of MetS traits and CoD (P < 0.001). A
      significant joint effect of MetS and CRP on the odds of CoD was observed.
      Conclusion. The study, using a nationally representative sample, extended
      previous studies by highlighting a significant MetS-CoD relationship and a joint
      effect of MetS and CRP on CoD. These novel findings add to our understanding of
      the association of neurometabolic disorders and cognition and have implications
      that may be relevant to primary care practice. 

PMID- 26317102
TI  - Roles of Integrins and Intracellular Molecules in the Migration and
      Neuritogenesis of Fetal Cortical Neurons: MEK Regulates Only the Neuritogenesis.
AB  - The roles of integrin subunits and intracellular molecules in regulating the
      migration and neuritogenesis of neurons isolated from 16.5 gestation days rat
      fetal cortices were examined using in vitro assays. Results showed that laminin
      supported the migration of fetal cortical neurons better than fibronectin and
      that the fetal cortical neurons migrated on laminin using beta1 and alpha3
      integrin subunits which make up the alpha3beta1 integrin receptor. On
      fibronectin, the migration was mediated by beta1 integrin subunit. Perturbation
      of src kinase, phospholipase C, or protein kinase C activity, inhibition of IP3
      receptor mediated calcium release, or chelation of intracellular calcium
      inhibited both migration and neuritogenesis, whereas inhibition of growth factor
      signaling via MEK inhibited only the neuritogenesis. The detection of alpha1 and
      alpha9 transcripts suggested that the migration of fetal cortical neurons may
      also be mediated by alpha1beta1 and alpha9beta1 integrin receptors. Results
      showed that calcium may regulate migration and neuritogenesis by maintaining
      optimum levels of microtubules in the fetal cortical neurons. It is concluded
      that the fetal cortical neurons are fully equipped with the integrin signaling
      cascade required for their migration and neuritogenesis, whereas crosstalk
      between the integrin and growth-factor signaling regulate only the
      neuritogenesis. 

PMID- 26317103
TI  - The Triglyceride Paradox in Stroke Survivors: A Prospective Study.
AB  - Objective. The purpose of our study was to understand the association between
      serum triglycerides and outcomes in acute ischemic stroke (AIS) patients.
      Methods. A cohort of all adult patients presenting to the Emergency Department
      (ED) with an AIS from March 2004 to December 2005 were selected. The lipid
      profile levels were measured within 24 hours of stroke onset. Demographics,
      admission stroke severity (NIHSS), functional outcome at discharge (modified
      Rankin Scale (mRS)), and mortality at 3 months were recorded. Results. The final
      cohort consisted of 334 subjects. A lower level of triglycerides at presentation
      was found to be significantly associated with worse National Institutes of Health
      Stroke Scale (NIHSS) (P = 0.004), worse mRS (P = 0.02), and death at 3 months (P
      = 0.0035). After adjusting for age and gender and NIHSS, the association between
      triglyceride and mortality at 3 months was not significant (P = 0.26).
      Conclusion. Lower triglyceride levels seem to be associated with a worse
      prognosis in AIS. 

PMID- 26317105
TI  - Teratogenic Effect of Crude Ethanolic Root Bark and Leaf Extracts of Rauwolfia
      vomitoria (Apocynaceae) on Nissl Substances of Albino Wistar Rat Fetuses.
AB  - Rauwolfia vomitoria is a plant used for the treatment of insanity. The possible
      adverse effects of crude ethanolic root bark and leaf extract of the plant on
      Nissl substances of albino Wistar rat fetuses were studied using 25 mature female
      Wistar rats. The animals were divided equally into 5 groups, labeled A, B, C, D,
      and E. Group A was the control, while groups B, C, D, and E were the
      experimental. The female rats were mated with the males overnight, and the sperm
      positive day was designated as day zero of pregnancy. Oral doses of 150 mg/kg and
      250 mg/kg body weight of the root bark extract were administered to groups B and
      C animals, respectively, while groups D and E animals received 150 mg/kg and 250
      mg/kg body weight of the leaf extract, respectively, from day 7 to 11 of
      gestation. On day 20 of gestation, the rats were sacrificed, the fetuses brains
      extracted, and the cerebral cortices excised and routinely processed for Nissl
      substances using Cresyl fast violet staining method. Results showed reduced
      staining intensity of Nissl substances in the treated groups, especially those
      that received the root extract. Thus, the herbs may have adverse effects on
      protein synthesis within the cerebral cortex. 

PMID- 26317104
TI  - The Effects of Sex and Chronic Restraint on Instrumental Learning in Rats.
AB  - Chronic stress has been shown to impact learning, but studies have been sparse or
      nonexistent examining sex or task differences. We examined the effects of sex and
      chronic stress on instrumental learning in adult rats. Rats were tested in an
      aversive paradigm with or without prior appetitive experience, and daily body
      weight data was collected as an index of stress. Relative to control animals,
      reduced body weight was maintained across the stress period for males (-7%, P <=
      .05) and females (-5%, P <= .05). For males, there were within-subject day-by-day
      differences after asymptotic transition, and all restrained males were delayed in
      reaching asymptotic performance. In contrast, stressed females were facilitated
      in appetitive and aversive-only instrumental learning but impaired during
      acquisition of the aversive transfer task. Males were faster than females in
      reaching the appetitive shaping criterion, but females were more efficient in
      reaching the appetitive tone-signaled criterion. Finally, an effect of task
      showed that while females reached aversive shaping criterion at a faster rate
      when they had prior appetitive learning, they were impaired in tone-signaled
      avoidance learning only when they had prior appetitive learning. These tasks
      reveal important nuances on the effect of stress and sex differences on goal
      directed behavior. 

PMID- 26317106
TI  - Subchronic Oral Bromocriptine Methanesulfonate Enhances Open Field Novelty
      Induced Behavior and Spatial Memory in Male Swiss Albino Mice.
AB  - This study set out to assess the neurobehavioral effects of subchronic, oral
      bromocriptine methanesulfonate using the open field and the Y-maze in healthy
      male mice. Sixty adult Swiss albino mice were assigned into three groups.
      Controls received normal saline, while test groups received bromocriptine
      methanesulfonate at 2.5 and 5 mg/kg/day, respectively, for a period of 21 days.
      Neurobehavioral tests were carried out on days 1 and 21 after administration.
      Open field assessment on day 1 after administration revealed significant increase
      in grooming at 2.5 and 5 mg/kg, while horizontal and vertical locomotion showed
      no significant changes. Day 1 also showed no significant changes in Y-maze
      alternation. On day 21, horizontal locomotion, rearing, and grooming were
      increased significantly at 2.5 and 5 mg/kg doses after administration; also,
      spatial memory was significantly enhanced at 2.5 mg/kg. In conclusion, the study
      demonstrates the ability of oral bromocriptine to affect neurobehavior in normal
      mice. It also suggests that there is a cumulative effect of oral bromocriptine on
      the behaviors studied with more changes being seen after subchronic
      administration rather than after a single oral dose. 

PMID- 26317107
TI  - Antinociceptive and Antioxidant Activities of Phytol In Vivo and In Vitro Models.
AB  - The objective of the present study was to evaluate the antinociceptive effects of
      phytol using chemical and thermal models of nociception in mice and to assess its
      antioxidant effects in vitro. Phytol was administered intraperitoneally (i.p.) to
      mice at doses of 25, 50, 100, and 200 mg/kg. In the acetic acid-induced writhing
      test, phytol significantly reduced the number of contortions compared to the
      control group (P < 0.001). In the formalin test, phytol reduced significantly the
      amount of time spent in paw licking in both phases (the neurogenic and
      inflammatory phases), this effect being more pronounced in the second phase (P <
      0.001). Phytol also provoked a significant increase in latency in the hot plate
      test. These antinociceptive effects did not impaire the motor performance, as
      shown in the rotarod test. Phytol demonstrated a strong antioxidant effect in
      vitro in its capacity to remove hydroxyl radicals and nitric oxide as well as to
      prevent the formation of thiobarbituric acid reactive substances (TBARS). Taken
      as a whole, these results show the pronounced antinociceptive effects of phytol
      in the nociception models used, both through its central and peripheral actions,
      but also its antioxidant properties demonstrated in the in vitro methods used. 

PMID- 26317108
TI  - Age-Dependent Increase of Absence Seizures and Intrinsic Frequency Dynamics of
      Sleep Spindles in Rats.
AB  - The risk of neurological diseases increases with age. In WAG/Rij rat model of
      absence epilepsy, the incidence of epileptic spike-wave discharges is known to be
      elevated with age. Considering close relationship between epileptic spike-wave
      discharges and physiologic sleep spindles, it was assumed that age-dependent
      increase of epileptic activity may affect time-frequency characteristics of sleep
      spindles. In order to examine this hypothesis, electroencephalograms (EEG) were
      recorded in WAG/Rij rats successively at the ages 5, 7, and 9 months. Spike-wave
      discharges and sleep spindles were detected in frontal EEG channel. Sleep
      spindles were identified automatically using wavelet-based algorithm.
      Instantaneous (localized in time) frequency of sleep spindles was determined
      using continuous wavelet transform of EEG signal, and intraspindle frequency
      dynamics were further examined. It was found that in 5-months-old rats epileptic
      activity has not fully developed (preclinical stage) and sleep spindles
      demonstrated an increase of instantaneous frequency from beginning to the end. At
      the age of 7 and 9 months, when animals developed matured and longer epileptic
      discharges (symptomatic stage), their sleep spindles did not display changes of
      intrinsic frequency. The present data suggest that age-dependent increase of
      epileptic activity in WAG/Rij rats affects intrinsic dynamics of sleep spindle
      frequency. 

PMID- 26317110
TI  - Impact of Age and Duration of Symptoms on Surgical Outcome of Single-Level
      Microscopic Anterior Cervical Discectomy and Fusion in the Patients with Cervical
      Spondylotic Radiculopathy.
AB  - We aim to evaluate the impact of age and duration of symptoms on surgical outcome
      of the patients with cervical spondylotic radiculopathy (CSR) who had been
      treated by single-level microscopic anterior cervical discectomy and fusion
      (ACDF). We retrospectively evaluated 68 patients (48 female and 20 male) with a
      mean age of 41.2 +/- 4.3 (ranged from 24 to 72 years old) in our Orthopedic
      Department, Imam Reza Hospital. They were followed up for 31.25 +/- 4.1 months
      (ranged from 25 to 65 months). Pain and disability were assessed by Visual
      Analogue Scale (VAS) and Neck Disability Index (NDI) questionnaires in
      preoperative and last follow-up visits. Functional outcome was eventually
      evaluated by Odom's criteria. Surgery could significantly improve pain and
      disability from preoperative 6.2 +/- 1.4 and 22.2 +/- 6.2 to 3.5 +/- 2.0 and 8.7
      +/- 5.2 (1-21) at the last follow-up visit, respectively. Satisfactory outcomes
      were observed in 89.7%. Symptom duration of more and less than six months had no
      effect on surgical outcome, but the results showed a statistically significant
      difference in NDI improvement in favor of the patients aged more than 45 years (P
      = 0.032), although pain improvement was similar in the two groups. 

PMID- 26317109
TI  - Language Development across the Life Span: A Neuropsychological/Neuroimaging
      Perspective.
AB  - Language development has been correlated with specific changes in brain
      development. The aim of this paper is to analyze the linguistic-brain
      associations that occur from birth through senescence. Findings from the
      neuropsychological and neuroimaging literature are reviewed, and the relationship
      of language changes observable in human development and the corresponding brain
      maturation processes across age groups are examined. Two major dimensions of
      language development are highlighted: naming (considered a major measure of
      lexical knowledge) and verbal fluency (regarded as a major measure of language
      production ability). Developmental changes in the brain lateralization of
      language are discussed, emphasizing that in early life there is an increase in
      functional brain asymmetry for language, but that this asymmetry changes over
      time, and that changes in the volume of gray and white matter are age-sensitive.
      The effects of certain specific variables, such as gender, level of education,
      and bilingualism are also analyzed. General conclusions are presented and
      directions for future research are suggested. 

PMID- 26317111
TI  - Age- and Sex-Dependent Changes in Androgen Receptor Expression in the Developing
      Mouse Cortex and Hippocampus.
AB  - During the perinatal period, male mice are exposed to higher levels of
      testosterone (T) than females, which promotes sexual dimorphism in their brain
      structures and behaviors. In addition to acting via estrogen receptors after
      being locally converted into estradiol by aromatase, T also acts directly through
      androgen receptor (AR) in the brain. Therefore, we hypothesized that AR
      expression in the developing mouse cortex and hippocampus was sexually dimorphic.
      To test our hypothesis, we measured and determined AR mRNA and protein levels in
      mouse cortex/hippocampus collected on the day of birth (PN0) and 7 (PN7), 14
      (PN14), and 21 (PN21) days after birth. We demonstrated that, as age advanced, AR
      mRNA levels increased in the cortex/hippocampus of both sexes but showed no sex
      difference. Two AR proteins, the full-length (110 kDa) and a smaller isoform (70
      kDa), were detected in the developing mouse cortex/hippocampus with an age
      dependent increase in protein levels of both AR isoforms at PN21 and a transient
      masculine increase in expression of the full-length AR protein on PN7. Thus, we
      conclude that the postnatal age and sex differences in AR protein expression in
      combination with the sex differences in circulating T may cause sexual
      differentiation of the mouse cortex/hippocampus. 

PMID- 26317112
TI  - Motorcycle-Related Traumatic Brain Injuries: Helmet Use and Treatment Outcome.
AB  - Summary. With increasing use of motorcycle as means of transport in developing
      countries, traumatic brain injuries from motorcycle crashes have been increasing.
      The only single gadget that protects riders from traumatic brain injury is crash
      helmet. Objective. The objectives were to determine the treatment outcome among
      traumatic brain injury patients from motorcycle crashes and the rate of helmet
      use among them. Methods. It was a prospective, cross-sectional study of
      motorcycle-related traumatic brain injury patients managed in our center from
      2010 to 2014. Patients were managed using our unit protocol for traumatic brain
      injuries. Data for the study were collected in accident and emergency, intensive
      care unit, wards, and outpatient clinic. The data were analyzed using
      Environmental Performance Index (EPI) info 7 software. Results. Ninety-six
      patients were studied. There were 87 males. Drivers were 65. Only one patient
      wore helmet. Majority of them were between 20 and 40 years. Fifty-three patients
      had mild head injuries. Favorable outcome among them was 84.35% while mortality
      was 12.5%. Severity of the injury affected the outcome significantly. Conclusion.
      Our study showed that the helmet use by motorcycle riders was close to zero
      despite the existing laws making its use compulsory in Nigeria. The outcome was
      related to severity of injuries. 

PMID- 26317113
TI  - Sex Differences and the Impact of Chronic Stress and Recovery on Instrumental
      Learning.
AB  - We have previously shown that 21-day chronic restraint stress impacts
      instrumental learning, but overall few studies have examined sex differences on
      the impact of stress on learning. We further examined sex differences in response
      to extended 42-day chronic stress on instrumental learning, as well as recovery
      from chronic stress. Rats were tested in aversive training tasks with or without
      prior appetitive experience, and daily body weight data was collected as an index
      of stress. Relative to control animals, reduced body weight was maintained from
      day 22 through day 42 across the stress period for males, but not for females.
      Stressed males had increased response speed and lower learning efficiency during
      appetitive acquisition and aversive learning. Males overall showed slower escape
      shaping times and more shock exposure. In contrast, stressed females showed
      slower appetitive response speeds and higher appetitive and aversive efficiency
      but overall reduced avoidance rates during acquisition and maintenance for
      transfer animals and during maintenance for aversive-only animals. These tasks
      reveal important nuances on the effect of stress on goal-directed behavior and
      further highlight sexually divergent effects on appetitive versus aversive
      motivation. Furthermore, these data underscore that systems are temporally
      impacted by chronic stress in a sexually divergent pattern. 

PMID- 26317115
TI  - The antiepileptic drug levetiracetam improves auditory gating in DBA/2 mice.
AB  - Schizophrenia is associated with deficits in P50 gating. This deficit is
      preclinically modeled in the DBA/2 mouse by depth recordings in the hippocampus.
      Neurobiologically, the deficit may be due to dysfunction in inhibitory circuitry.
      It follows that anti-epileptic drugs which impact this circuitry, such as
      levetiracetam (LEV), may improve gating. To that end, the goal of this study was
      to evaluate the ability of LEV to normalize sensory gating in the DBA/2 mouse.
      Gating of the murine analog of the P50, the P20-N40, was evaluated from in vivo
      hippocampal recordings in 39 male DBA/2 mice. Gating effects were evaluated using
      four doses of LEV (3, 10, 30, and 100 mg/kg). The 10 mg/kg dose improved P20-N40
      gating (P = 0.016). No other doses significantly affected gating. Low-dose LEV
      may improve P20-N40 gating in the DBA/2 mouse model of schizophrenia. Low-doses
      of LEV may improve P20-N40 gating in the DBA/2 mouse model of schizophrenia and
      warrant further investigation in the illness.

PMID- 26317114
TI  - Vascular protective effects of Angiotensin Receptor Blockers: Beyond Blood
      pressure.

PMID- 26317117
TI  - Genomic and immunohistochemical analysis in human adrenal cortical neoplasia
      reveal beta-catenin mutations as potential prognostic biomarker.
AB  - Evaluation for malignancy of the adrenal cortex, adrenal cortical carcinoma
      (ACC), is a challenge in surgical pathology due to its relative rarity and
      histologic overlap with its benign counterpart, adrenocortical adenoma (ACA). We
      characterized a cohort of human ACC and ACA, including a molecular screen, with a
      goal of identifying potential diagnostic adjuncts. Thirty-six cases of ACC
      underwent histologic and clinical review. In the 31 ACC cases with available
      material and a cohort of 10 ACA cases, a multiplex nucleotide amplification
      molecular screen from formalin-fixed, paraffin-embedded tissue was peformed. ACCs
      demonstrated a wide variety of clinical and histologic characteristics with
      overall poor but unpredictable survival for subjects with ACC. By mutational
      screen, 12/31 (38.7%) carcinomas harbored CTNNB1 mutations, 1 with an additional
      TP53 mutation; 1 case each had isolated APC and TP53 mutations; 16 were wild-type
      for all tested loci; and 1 case demonstrated repeated assay failures. Two of the
      10 ACA (20%) demonstrated CTNNB1 mutations by mutational screen, with no
      additional mutations. Immunohistochemistry for beta-catenin was performed and
      compared with the results of the molecular screen. Strong nuclear beta-catenin
      immunopositivity corresponded to the presence of CTNNB1 mutation by genotyping in
      10 of 12 cases (83% sensitivity); the mismatched case(s) demonstrated strong
      membranous staining by immunohistochemistry. Seventeen of the 18 cases without
      CTNNB1 mutation showed membranous staining or did not stain (94% specificity);
      the mismatched case demonstrated scattered (<10%) positive nuclei. Both mutations
      in ACA were corroborated with immunohistochemistry for beta-catenin. No
      histomorphologic parameter appeared dominant in lesions with a particular
      mutational status. Based on these results, mutational status of CTNNB1 in adrenal
      cortical neoplasms can be predicted with reasonable accuracy by
      immunohistochemical cellular localization. Nuclear localization of beta-catenin
      by immunostain may be helpful in analysis of select lesions of the adrenal cortex
      whose biological behavior is uncertain from clinical and histologic information;
      a larger cohort is required to test this hypothesis.

PMID- 26317116
TI  - Key principles of miRNA involvement in human diseases.
AB  - Although rapid progress in our understanding of the functions of miRNA has been
      made by experimentation and computational approach, a considerable effort still
      has to be done in determining the general principles that govern the miRNA's mode
      of action in human diseases. We will further discuss how these principles are
      being progressively approached by molecular studies, as well as the importance of
      miRNA in regulating different target genes and functions in specific biological
      contexts. There is a great demand to understand the principles of context -
      specific miRNA target recognition in order to design future experiments and
      models of normal developmental and disease states.

PMID- 26317118
TI  - Initial In-Vivo Analysis of 3D Heterogeneous Brain Computations for Model-Updated
      Image-Guided Neurosurgery.
AB  - Registration error resulting from intraoperative brain shift due to applied
      surgical loads has long been recognized as one of the most challenging problems
      in the field of frameless stereotactic neurosurgery. To address this problem, we
      have developed a 3-dimensional finite element model of the brain and have begun
      to quantify its predictive capability in an in vivo porcine model. Previous
      studies have shown that we can predict the average total displacement within 15%
      and 6.6% error using intraparenchymal and temporal deformation sources,
      respectively, under relatively simple model assumptions. In this paper, we
      present preliminary results using a heterogeneous model with an expanding
      temporally located mass and show that we are capable of predicting an average
      total displacement to 5.7% under similar model initial and boundary conditions.
      We also demonstrate that our approach can be viewed as having the capability of
      recapturing approximately 75% of the registration inaccuracy that may be
      generated by preoperative-based image-guided neurosurgery.

PMID- 26317119
TI  - Model-Updated Image-Guided Neurosurgery Using the Finite Element Method:
      Incorporation of the Falx Cerebri.
AB  - Surgeons using neuronavigation have realized the value of image guidance for
      feature recognition as well as for the precise application of surgical
      instruments. Recently, there has been a growing concern about the extent of
      intraoperative misregistration due to tissue deformation. Intraoperative imaging
      is currently under evaluation but limitations related to cost effectiveness and
      image clarity have made its wide spread adoption uncertain. As a result,
      computational model-guided techniques have generated considerable appeal as an
      alternative approach. In this paper, we report our initial experience with
      enhancing our brain deformation model by explicitly adding the falx cerebri. The
      simulations reported show significant differences in subsurface deformation with
      the falx serving to damp the communication of displacement between hemispheres by
      as much as 4 mm. Additionally, these calculations, based on a human clinical
      case, demonstrate that while cortical shift predictions correlate well with
      various forms of the model (70-80% of surface motion recaptured), substantial
      differences in subsurface deformation occurs suggesting that subsurface
      validation of model-guided techniques will be important for advancing this
      concept.

PMID- 26317120
TI  - Model-Updated Image-Guided Neurosurgery: Preliminary Analysis Using
      Intraoperative MR.
AB  - In this paper, initial clinical data from an intraoperative MR system are
      compared to calculations made by a three-dimensional finite element model of
      brain deformation. The preoperative and intraoperative MR data was collected on a
      patient undergoing a resection of an astrocytoma, grade 3 with non-enhancing and
      enhancing regions. The image volumes were co-registered and cortical
      displacements as well as subsurface structure movements were measured
      retrospectively. These data were then compared to model predictions undergoing
      intraoperative conditions of gravity and simulated tumor decompression. Computed
      results demonstrate that gravity and decompression effects account for
      approximately 40% and 30%, respectively, totaling a 70% recovery of shifting
      structures with the model. The results also suggest that a non-uniform
      decompressive stress distribution may be present during tumor resection. Based on
      this preliminary experience, model predictions constrained by intraoperative
      surface data appear to be a promising avenue for correcting brain shift during
      surgery. However, additional clinical cases where volumetric intraoperative MR
      data is available are needed to improve the understanding of tissue mechanics
      during resection.

PMID- 26317121
TI  - Model-Updated Image Guidance: A Statistical Approach to Gravity-Induced Brain
      Shift.
AB  - Compensating for intraoperative brain shift using computational models has been
      used with promising results. Since computational time is an important factor
      during neurosurgery, a prior knowledge of a patient's orientation and changes in
      tissue buoyancy force would be valuable information to aid in predicting shift
      due to gravitational forces. Since the latter is difficult to quantify
      intraoperatively, a statistical model for predicting intraoperative brain
      deformations due to gravity is reported. This statistical model builds on a
      computational model developed earlier. For a given set of patient's orientation
      and amount of CSF drainage, the intraoperative brain shift is calculated using
      the computational model. These displacements are then validated against measured
      displacements to predict the intraoperative brain shift. Though initial results
      are promising, further study is needed before the statistical model can be used
      for model-updated image-guided surgery.

PMID- 26317122
TI  - Cortical Shift Tracking Using a Laser Range Scanner and Deformable Registration
      Methods.
AB  - A novel brain shift tracking protocol is introduced in this paper which utilizes
      laser range scan (LRS) data and 2D deformable image registration. This protocol
      builds on previous efforts to incorporate intra-operative LRS data into a model
      updated image guided surgery paradigm for brain shift compensation. The shift
      tracking method employs the use of a LRS system capable of capturing textures of
      the intra-operative scene during range data acquisition. Textures from serial
      range images are then registered using a 2D deformable registration approach that
      uses local support radial basis functions and mutual information. Given the
      deformation field provided by the registration, 3D points in serial LRS datasets
      can then be tracked. Results from this paper indicate that the error associated
      with tracking brain movement is 1.1mm on average given brain shifts of
      approximately 20.5mm. Equally important, a strategy is presented to rapidly
      acquire intra-operative measurements of shift which are compatible with model
      based strategies for brain deformation compensation.

PMID- 26317123
TI  - CLINICAL/MEDICAL OUTCOME PREDICTION BY NEURAL NETWORKS WITH STATISTICAL
      ENHANCEMENT.
AB  - Neural networks offer a powerful new approach to information processing through
      their ability to generalize from a specific training data set. The success of
      this approach has raised interesting new possibilities of incorporating
      statistical methodology in order to enhance their predictive ability. This paper
      reports on two complementary methods of prediction. one using neural networks and
      the other using traditional statistical methods. The two methods are compared on
      the basis of their prediction applied to standardized developmental infant
      outcome measures using preselected infant and maternal variables measured at
      birth. Three neural network algorithms were employed. In our study, no one
      network outperformed the other two consistently. The neural networks provided
      significantly better results than the regression model in terms of variation and
      prediction of extreme outcomes. Finally we demonstrated that selection of
      relevant input variables through statistical means can produce a reduced network
      structure with no loss in predictive ability.

PMID- 26317124
TI  - Hem12, an enzyme of heme biosynthesis pathway, is monoubiquitinated by Rsp5
      ubiquitin ligase in yeast cells.
AB  - Heme biosynthesis pathway is conserved in yeast and humans and hem12 yeast
      mutants mimic porphyria cutanea tarda (PCT), a hereditary human disease caused by
      mutations in the UROD gene. Even though mutations in other genes also affect UROD
      activity and predispose to sporadic PCT, the regulation of UROD is unknown. Here,
      we used yeast as a model to study regulation of Hem12 by ubiquitination and
      involvement of Rsp5 ubiquitin ligase in this process. We found that Hem12 is
      monoubiquitinated in vivo by Rsp5. Hem12 contains three conserved lysine residues
      located on the protein surface that can potentially be ubiquitinated and lysine
      K8 is close to the 36-LPEY-39 (PY) motif which binds WW domains of the Rsp5
      ligase. The hem12-K8A mutation results in a defect in cell growth on a glycerol
      medium at 38 degrees C but it does not affect the level of Hem12. The hem12
      L36A,P37A mutations which destroy the PY motif result in a more profound growth
      defect on both, glycerol and glucose-containing media. However, after several
      passages on the glucose medium, the hem12-L36A,P37A cells adapt to the growth
      medium owing to higher expression of hem12-L36A,P37A gene and higher stability of
      the mutant Hem12-L36A,P37A protein. The Hem12 protein is downregulated upon heat
      stress in a Rsp5-independent way. Thus, Rsp5-dependent Hem12 monoubiquitination
      is important for its functioning, but not required for its degradation. Since
      Rsp5 has homologs among the Nedd4 family of ubiquitin ligases in humans, a
      similar regulation by ubiquitination might be also important for functioning of
      the human UROD. 

PMID- 26317125
TI  - Non-enzymatic activation of prothrombin induced by interaction with fibrin beta26
      42 region.
AB  - We have discovered that addition of monomeric desAB fibrin to prothrombin leads
      to appearance of the thrombin-like activity of prothrombin towards S2238
      chromogenic substrate. DesA and desABbeta(15-42)2 fibrin forms did not cause any
      activation of prothrombin. From this observation we could suggested that amino
      acid residues of the 15-42 fragment of BbetaN-domain presented in desAB fibrin,
      cleaved in desABbeta(15-42)2 fibrin and protected in desA fibrin, play a crucial
      role in the non-enzymatic activation of prothrombin. To identify the Bbeta amino
      acid residues involved in the fibrin-prothrombin binding we used monoclonal
      antibodies 1-5G and 2d2a with epitopes in Bbeta26-42 and Bbeta12-26 fibrin
      fragments respectively. The thrombin-like activity in the mixture of prothrombin
      and desAB fibrin was monitored in the presence of each of these monoclonal
      antibodies. It was found that anti-Bbeta12-26 antibody does not exhibit any
      inhibitory effect on the thombin-like activity of the mixture. In contrast,
      adding of Bbeta26-42 antibody into the mixture of desAB fibrin with prothrombin
      diminished the thrombin-like activity by 70%. Recombinant dimeric peptides
      Bbeta(15-44)2 and Bbeta(15-66)2 that mimic amino acid residues in fibrin were
      also tested for their ability to activate prothrombin. It was found that both
      peptides were able to induce non-enzymatic activation of prothrombin. The
      activation was more evident in the case of Bbeta(15-44)2 peptide. From the data
      obtained we can conclude that desAB fibrin binds to prothrombin through the
      Bbeta26-42 amino acid residues and the formation of such a complex caused a non
      enzymatic activation of prothrombin. 

PMID- 26317126
TI  - Searching for association of the CAG repeat polymorphism in the mitochondrial DNA
      polymerase gamma gene (POLG) with colorectal cancer.
AB  - Mitochondrial DNA polymerase gamma (POLG) is the only DNA polymerase involved in
      maintaining the mitochondrial genome. Recent studies demonstrated an association
      of CAG repeat polymorphism in the second exon of POLG gene with the risk of
      cancer. We investigated the CAG repeat variability in the POLG gene in tumor and
      non-tumor tissues from colorectal cancer patients and in DNA samples isolated
      from blood obtained from age-matched healthy persons. Somatically occuring CAG
      repeat alterations in cancer tissues have been observed in 10% of patients, but
      no association has been found between the CAG repeat variants in the POLG gene
      and colorectal cancer risk. 

PMID- 26317127
TI  - Rapid normalization of severe hypercholesterolemia mediated by lipoprotein X
      after liver transplantation in a patient with cholestasis - a case report.
AB  - Hypercholesterolemia is a common disorder in adult population, but total
      cholesterol concentrations beyond 1000 mg/dl occur rarely, and are found in
      patients with homozygous familial hypercholesterolemia and familial lecithin
      cholesterol acyltransferase deficiency, in chronic graft-versus-host disease of
      the liver, after intravenous infusion of fat emulsion (intralipid), in newborn
      infants with immature liver function, and in obstructive biliary cholestasis.
      Cholestasis induces a dramatic increase in plasma cholesterol and the appearance
      of an abnormal lipoprotein, lipoprotein X (LpX), in the plasma. We report a case
      of severe hypercholesterolemia mediated by LpX in a patient transplanted for
      primary biliary cirrhosis (PBC), who was qualified for liver re-transplantation
      (re-LTx) due to chronic cholestasis. Four months after re-LTx, the cholesterol
      concentration was normal. The problems in diagnosis and treatment are discussed. 

PMID- 26317128
TI  - RASMOL AB - new functionalities in the program for structure analysis.
AB  - For many years RasMol was one of the most used programs for molecular
      visualization. It was an excellent tool due to its simplicity and its low demand
      of computer power. Today it is replaced by OpenGL programs, which have excellent
      graphics that new computers can additionally handle. Molecular graphics is one of
      the best tools for the analysis of biomolecular data. With high efficiency and a
      low demand of computer power, RasMol can still be used as a quick and handy tool
      used for the analysis of biomolecular structures with good results. In this
      paper, we describe modifications to the RasMol program, as implemented on the
      base of RasMol AB 2. We introduced several new functions, namely: the
      identification of histidine isomers, and advanced structural selection and macro
      capabilities (as implemented in the point-click menu), which result in an
      increase in the speed and accuracy of structural analyses. The program can be
      downloaded from the project page: http://etoh.chem.univ.gda.pl/rasmol/. 

PMID- 26317129
TI  - Application of the High Resolution Melting analysis for genetic mapping of
      Sequence Tagged Site markers in narrow-leafed lupin (Lupinus angustifolius L.).
AB  - Sequence tagged site (STS) markers are valuable tools for genetic and physical
      mapping that can be successfully used in comparative analyses among related
      species. Current challenges for molecular markers genotyping in plants include
      the lack of fast, sensitive and inexpensive methods suitable for sequence variant
      detection. In contrast, high resolution melting (HRM) is a simple and high
      throughput assay, which has been widely applied in sequence polymorphism
      identification as well as in the studies of genetic variability and genotyping.
      The present study is the first attempt to use the HRM analysis to genotype STS
      markers in narrow-leafed lupin (Lupinus angustifolius L.). The sensitivity and
      utility of this method was confirmed by the sequence polymorphism detection based
      on melting curve profiles in the parental genotypes and progeny of the narrow
      leafed lupin mapping population. Application of different approaches, including
      amplicon size and a simulated heterozygote analysis, has allowed for successful
      genetic mapping of 16 new STS markers in the narrow-leafed lupin genome. 

PMID- 26317130
TI  - Fluorescence resonance energy transfer-based ratiometric fluorescent assay for
      highly sensitive and selective determination of sulfide anions.
AB  - A novel and effective ratiometric fluorescence strategy was developed for
      rapidly, sensitively and selectively probing sulfide anions (S(2-)). A dual
      emission nanosensor was prepared by covalently attaching fluorescent carbon
      nanoparticles (CNPs) to gold nanoclusters (Au NCs), triggering the sensing
      mechanism of fluorescence resonance energy transfer (FRET) from CNPs (donor) to
      Au NCs (acceptor). Once S(2-) was added, considerable fluorescence recovery of
      CNPs and quenching of Au NCs were observed due to the inhibition of FRET progress
      via the formation of Au2S. The ratiometric probe showed good, specific S(2-)
      sensing behavior and high sensitivity with a detection limit of 18 nM.
      Significantly, the assay was successfully employed to determine the S(2-) content
      in biological and water samples, presenting immense promise in the biological and
      environmental fields. 

PMID- 26317131
TI  - Composite biopolymers for bone regeneration enhancement in bony defects.
AB  - For the past century, various biomaterials have been used in the treatment of
      bone defects and fractures. Their role as potential substitutes for human bone
      grafts increases as donors become scarce. Metals, ceramics and polymers are all
      materials that confer different advantages to bone scaffold development. For
      instance, biocompatibility is a highly desirable property for which naturally
      derived polymers are renowned. While generally applied separately, the use of
      biomaterials, in particular natural polymers, is likely to change, as biomaterial
      research moves towards mixing different types of materials in order to maximize
      their individual strengths. This review focuses on osteoconductive biocomposite
      scaffolds which are constructed around natural polymers and their performance at
      the in vitro/in vivo stages and in clinical trials. 

PMID- 26317133
TI  - Bidentate nitroxide ligands stable toward oxidative redox cycling and their
      complexes with cerium and lanthanum.
AB  - We report the synthesis of 1,3-bis[(2'-tertbutyl)hydroxyaminophenyl]benzene
      (H2arene-diNOx) and its metal complexes, Ce(arene-diNOx)2 (1) and [(py)2K(18
      crown-6)][La(arene-diNOx)2] (2). Electrochemical studies demonstrated that the
      H2arene-diNOx, bidentate nitroxide ligands significantly stabilized the
      Ce(IV/III) redox couple to -1.74 V versus Fc/Fc(+). Moreover, a reversible
      oxidation wave was observed for 1 at -0.37 V, leading to a novel, stable redox
      active nitroxide ligand. DFT calculations confirmed that the observed oxidation
      is assignable to one of the nitroxide groups.

PMID- 26317132
TI  - Nano-mole scale sequential signal assignment by (1)H-detected protein solid-state
      NMR.
AB  - We present a 3D (1)H-detected solid-state NMR (SSNMR) approach for main-chain
      signal assignments of 10-100 nmol of fully protonated proteins using ultra-fast
      magic-angle spinning (MAS) at ~80 kHz by a novel spectral-editing method, which
      permits drastic spectral simplification. The approach offers ~110 fold time
      saving over a traditional 3D (13)C-detected SSNMR approach. 

PMID- 26317135
TI  - Peter Randall, M.D., 1923 to 2014.

PMID- 26317136
TI  - Preface.

PMID- 26317137
TI  - Activation of auxin signalling counteracts photorespiratory H2O2-dependent cell
      death.
AB  - The high metabolic flux through photorespiration constitutes a significant part
      of the carbon cycle. Although the major enzymatic steps of the photorespiratory
      pathway are well characterized, little information is available on the functional
      significance of photorespiration beyond carbon recycling. Particularly important
      in this respect is the peroxisomal catalase activity which removes
      photorespiratory H2O2 generated during the oxidation of glycolate to glyoxylate,
      thus maintaining the cellular redox homeostasis governing the perception,
      integration and execution of stress responses. By performing a chemical screen,
      we identified 34 small molecules that alleviate the negative effects of
      photorespiration in Arabidopsis thaliana mutants lacking photorespiratory
      catalase (cat2). The chlorophyll fluorescence parameter photosystem II maximum
      efficiency (Fv'/Fm') was used as a high-throughput readout. The most potent
      chemical that could rescue the photorespiratory phenotype of cat2 is a pro-auxin
      that contains a synthetic auxin-like substructure belonging to the phenoxy
      herbicide family, which can be released in planta. The naturally occurring indole
      3-acetic acid (IAA) and other chemically distinct synthetic auxins also inhibited
      the photorespiratory-dependent cell death in cat2 mutants, implying a role for
      auxin signalling in stress tolerance.

PMID- 26317138
TI  - Preface to cognitive enhancement.

PMID- 26317139
TI  - Part 1. Basic approaches and perspectives.

PMID- 26317140
TI  - Part II. Cognitive domains for pharmacological intervention: implications for
      neuropsychiatric and neurological illnesses.

PMID- 26317141
TI  - Part III. Developmental disorders, alternative approaches, and emerging
      technologies.

PMID- 26317142
TI  - Preface by the editors.

PMID- 26317143
TI  - How do surgeons approach breast cancer surgery in Turkey?  A national survey.
AB  - BACKGROUND: The aim of this study was to investigate the experience, practice and
      approaches of general surgeons in relation to the treatment of breast cancer in
      Turkey. METHODS: A survey was conducted between November 2012 and February 2013
      with 453 general surgeons who claimed to perform breast surgery. Initial and most
      preferred approaches for breast cancer surgery and demographic features of
      participants were questioned. Initial approaches of surgeons for a suspected
      breast mass were assessed with a clinical scenario. RESULTS: A total of 12.6 % of
      practicing general surgeons in Turkey responded to the survey. A
      multidisciplinary assessment was employed by 57.2 % of participants. The most
      frequently used diagnostic tool was needle biopsies (64.9 %) and the most
      frequently performed surgery for early stage cancers was breast-conserving
      surgery (72.2 %). The initial approach for locally advanced breast cancer was
      neoadjuvant chemotherapy (59.8 %) and mastectomy for metastatic cancer (22.7 %).
      Sentinel lymph node biopsies were utilized by 59.2 % of participants by different
      methods in appropriate cases. Oncoplastic breast surgery was performed by 9.0 %
      of participants, frequently or constantly. The surgeons' initial approaches for
      the clinical scenario were imaging (56.7 %) and biopsy (40.6 %). CONCLUSIONS:
      Although there are efforts to improve up-to-date approaches towards breast cancer
      surgery by surgeons, currently there are significant inadequacies for evidence
      based medicine practices.

PMID- 26317144
TI  - Consecutive Morphology Controlling Operations for Highly Reproducible
      Mesostructured Perovskite Solar Cells.
AB  - Perovskite solar cells have shown high photovoltaic performance but suffer from
      low reproducibility, which is mainly caused by low uniformity of the active
      perovskite layer in the devices. The nonuniform perovskites further limit the
      fabrication of large size solar cells. In this work, we control the morphology of
      CH3NH3PbI3 on a mesoporous TiO2 substrate by employing consecutive antisolvent
      dripping and solvent-vapor fumigation during spin coating of the precursor
      solution. The solvent-vapor treatment is found to enhance the perovskite pore
      filling and increase the uniformity of CH3NH3PbI3 in the porous scaffold layer
      but slightly decrease the uniformity of the perovskite capping layer. An
      additional antisolvent dripping is employed to recover the uniform perovskite
      capping layer. Such consecutive morphology controlling operations lead to highly
      uniform perovskite in both porous and capping layers. By using the optimized
      perovskite deposition procedure, the reproducibility of mesostructured solar
      cells was greatly improved such that a total of 40 devices showed an average
      efficiency of 15.3% with a very small standard deviation of 0.32. Moreover, a
      high efficiency of 14.9% was achieved on a large-size cell with a working area of
      1.02 cm(2). 

PMID- 26317145
TI  - Living arrangements and suicidal ideation among the Korean older adults.
AB  - OBJECTIVES: This study examines how living arrangements are associated with
      suicidal ideation for older adults in South Korea, which has the highest suicide
      rate among OECD countries, and a particularly high suicide rate for older
      persons. METHODS: Analyzing a sample of 5795 women and 3758 men aged 65 and older
      from a nationwide representative cross-sectional data-set, we examined how many
      older adults think about suicide over a one-year period, why they think about
      suicide, and whether living arrangements are associated with suicidal ideation.
      RESULTS: About 1 out of 12 respondents in our sample reported suicidal ideation.
      While women and men did not differ in the prevalence of suicidal ideation, women
      attributed their suicidal feelings to health problems, while men attributed
      theirs to economic difficulties. Logistic regression results indicated that
      living arrangements are associated with suicidal ideation for men but not women.
      Older men living with a spouse were less likely to have suicidal ideation than
      older men with other living arrangements (i.e., living alone, living with
      children without spouse, living with spouse, and others). CONCLUSIONS: Our
      results highlight the importance of living arrangements to older men's suicidal
      ideation. We discuss gender differences in the implications of living
      arrangements to suicidal ideation within the context of Confucian culture.

PMID- 26317146
TI  - Biotags Based on Surface-Enhanced Raman Can Be as Bright as Fluorescence Tags.
AB  - Surface enhanced Raman spectroscopy (SERS) is a powerful analytical technique
      that has been proposed as a substitute for fluorescence for biological imaging
      and detection but is not yet commercially utilized. The reason lies primarily in
      the lower intensity and poor reproducibility of most metal nanoparticle-based
      tags as compared to their fluorescence-based counterparts. Here, using a
      technique that scrupulously preserves the same number of dye molecules in both
      the SERS and fluorescence measurements, we show that SERS-based biotags (SBTs)
      with highly reproducible optical properties can be nanoengineered such that their
      brightness is at least equal to that of fluorescence-based tags. 

PMID- 26317147
TI  - Whole blood EBV-DNA: A surrogate for immune dysfunction in aggressive lymphoma?

PMID- 26317148
TI  - Dietary recommendations for the prevention of depression.
AB  - BACKGROUND: Major depressive disorder is a common, chronic condition that imposes
      a substantial burden of disability globally. As current treatments are estimated
      to address only one-third of the disease burden of depressive disorders, there is
      a need for new approaches to prevent depression or to delay its progression.
      While in its early stages, converging evidence from laboratory, population
      research, and clinical trials now suggests that dietary patterns and specific
      dietary factors may influence the risk for depression. However, largely as a
      result of the recency of the nutritional psychiatry field, there are currently no
      dietary recommendations for depression. AIM: The aim of this paper is to provide
      a set of practical dietary recommendations for the prevention of depression,
      based on the best available current evidence, in order to inform public health
      and clinical recommendations. RESULTS: Five key dietary recommendations for the
      prevention of depression emerged from current published evidence. These comprise:
      (1) follow 'traditional' dietary patterns, such as the Mediterranean, Norwegian,
      or Japanese diet; (2) increase consumption of fruits, vegetables, legumes,
      wholegrain cereals, nuts, and seeds; (3) include a high consumption of foods rich
      in omega-3 polyunsaturated fatty acids; (4) replace unhealthy foods with
      wholesome nutritious foods; (5) limit your intake of processed-foods, 'fast'
      foods, commercial bakery goods, and sweets. CONCLUSION: Although there are a
      number of gaps in the scientific literature to date, existing evidence suggests
      that a combination of healthful dietary practices may reduce the risk of
      developing depression. It is imperative to remain mindful of any protective
      effects that are likely to come from the cumulative and synergic effect of
      nutrients that comprise the whole-diet, rather than from the effects of
      individual nutrients or single foods. As the body of evidence grows from
      controlled intervention studies on dietary patterns and depression, these
      recommendations should be modified accordingly.

PMID- 26317149
TI  - An Epidemiological Survey of Cachexia in Advanced Cancer Patients and Analysis on
      Its Diagnostic and Treatment Status.
AB  - Recently, an international consensus diagnostic criterion for cancer cachexia was
      proposed. The aim of the study is to assess the prevalence of cachexia in
      patients with advanced cancer and to assess the current status of the diagnosis
      and management of cancer cachexia. A total of 390 patients with advanced cancer
      were included. There were 140 patients with cachexia and the prevalence was
      35.9%. The prevalence was highest in pancreatic cancer (88.9%), followed by
      gastric cancer (76.5%) and esophageal cancer (52.9%). Sixty-three patients with
      cancer cachexia have CT scans available for muscle mass evaluation and 98.4% were
      sarcopenic. Cachectic patients have a significantly lower overall quality of life
      and a higher symptom burden. According to oncology physicians, only 33 patients
      were considered to have cancer cachexia. The false negative rate amounted to
      76.4%. The positive rate was related to the body mass index and Eastern
      Cooperative Oncology Group performance status of the patients. There were few
      types of pharmacological approaches for cancer cachexia and more than half of
      cachectic patients did not receive any anticachexia treatment. These results
      indicate that the prevalence of cachexia in advanced cancer patients was high.
      However, cancer cachexia was rarely recognized and clinical management for cancer
      cachexia was very inadequate. 

PMID- 26317150
TI  - EARLY BUD-BREAK1 (EBB1) defines a conserved mechanism for control of bud-break in
      woody perennials.
AB  - Bud-break is an environmentally and economically important trait in trees, shrubs
      and vines from temperate latitudes. Poor synchronization of bud-break timing with
      local climates can lead to frost injuries, susceptibility to pests and pathogens
      and poor crop yields in fruit trees and vines. The rapid climate changes outpace
      the adaptive capacities of plants to respond through natural selection. This is
      particularly true for trees which have long generation cycle and thus the
      adaptive changes are significantly delayed. Therefore, to devise appropriate
      breeding and conservation strategies, it is imperative to understand the
      molecular underpinnings that govern dormancy mechanisms. We have recently
      identified and characterized the poplar EARLY BUD-BREAK 1 (EBB1) gene. EBB1 is a
      positive regulator of bud-break and encodes a transcription factor from the
      AP2/ERF family. Here, using comparative and functional genomics approaches we
      show that EBB1 function in regulation of bud-break is likely conserved across
      wide range of woody perennial species with importance to forestry and
      agriculture. 

PMID- 26317152
TI  - Cellular Response of Stem Cells on Nanofibrous Scaffold for Ocular Surface
      Bioengineering.
AB  - In this study, the human limbus stem cell was used to evaluate the phenotypic
      profile, viability, proliferation, and attachment ability of nanofibrous poly (3
      hydroxybutyrate-co-3-hydroxyvalerate) substrates. Results indicated that the all
      substrates were highly biocompatible, as firmly anchored to the substrates, and
      were able to retain a normal corneal stem cell phenotype. Immunocytochemistry
      results revealed no change in the expression profile of cells grown on
      nanofibrous substrate when compared with those grown on amniotic membrane. In
      addition, nanofibrous substrate provides not only a milieu supporting cells
      expansion, but also serve as a useful alternative carrier for ocular surface
      engineering. 

PMID- 26317151
TI  - A preliminary study for determination of three-dimensional root apex position of
      the maxillary teeth using camera calibration technology.
AB  - OBJECTIVES: To propose a novel method for determining the three-dimensional (3D)
      root apex position of maxillary teeth using a two-dimensional (2D) panoramic
      radiograph image and a 3D virtual maxillary cast model. METHODS: The subjects
      were 10 adult orthodontic patients treated with non-extraction. The multiple
      camera matrices were used to define transformative relationships between tooth
      images of the 2D panoramic radiographs and the 3D virtual maxillary cast models.
      After construction of the root apex-specific projective (RASP) models,
      overdetermined equations were used to calculate the 3D root apex position with a
      direct linear transformation algorithm and the known 2D co-ordinates of the root
      apex in the panoramic radiograph. For verification of the estimated 3D root apex
      position, the RASP and 3D-CT models were superimposed using a best-fit method.
      Then, the values of estimation error (EE; mean, standard deviation, minimum error
      and maximum error) between the two models were calculated. RESULTS: The
      intraclass correlation coefficient values exhibited good reliability for the
      landmark identification. The mean EE of all root apices of maxillary teeth was
      1.88 mm. The EE values, in descending order, were as follows: canine, 2.30 mm;
      first premolar, 1.93 mm; second premolar, 1.91 mm; first molar, 1.83 mm; second
      molar, 1.82 mm; lateral incisor, 1.80 mm; and central incisor, 1.53 mm.
      CONCLUSIONS: Camera calibration technology allows reliable determination of the
      3D root apex position of maxillary teeth without the need for 3D-CT scan or tooth
      templates.

PMID- 26317154
TI  - Quantum Diffusion-Controlled Chemistry: Reactions of Atomic Hydrogen with Nitric
      Oxide in Solid Parahydrogen.
AB  - Our group has been working to develop parahydrogen (pH2) matrix isolation
      spectroscopy as a method to study low-temperature condensed-phase reactions of
      atomic hydrogen with various reaction partners. Guided by the well-defined
      studies of cold atom chemistry in rare-gas solids, the special properties of
      quantum hosts such as solid pH2 afford new opportunities to study the analogous
      chemical reactions under quantum diffusion conditions in hopes of discovering new
      types of chemical reaction mechanisms. In this study, we present Fourier
      transform infrared spectroscopic studies of the 193 nm photoinduced chemistry of
      nitric oxide (NO) isolated in solid pH2 over the 1.8 to 4.3 K temperature range.
      Upon short-term in situ irradiation the NO readily undergoes photolysis to yield
      HNO, NOH, NH, NH3, H2O, and H atoms. We map the postphotolysis reactions of
      mobile H atoms with NO and document first-order growth in HNO and NOH reaction
      products for up to 5 h after photolysis. We perform three experiments at 4.3 K
      and one at 1.8 K to permit the temperature dependence of the reaction kinetics to
      be quantified. We observe Arrhenius-type behavior with a pre-exponential factor
      of A = 0.036(2) min(-1) and Ea = 2.39(1) cm(-1). This is in sharp contrast to
      previous H atom reactions we have studied in solid pH2 that display definitively
      non-Arrhenius behavior. The contrasting temperature dependence measured for the H
      + NO reaction is likely related to the details of H atom quantum diffusion in
      solid pH2 and deserves further study. 

PMID- 26317155
TI  - Solid-Phase Synthesis, Hybridizing Ability, Uptake, and Nuclease Resistant
      Profiles of Position-Selective Cationic and Hydrophobic Phosphotriester
      Oligonucleotides.
AB  - Analogues of oligonucleotides and mononucleotides with hydrophobic and/or
      cationic phophotriester functionalities often generate an improvement in target
      affinity and cellular uptake. Here we report the synthesis of phosphotriester
      oligodeoxyribonucleotides (ODNs) that are stable to the conditions used for their
      preparation. The method has been demonstrated by introducing phosphoramidite
      synthons where N-benzyloxycarbonyl (Z) protected amino alcohols replace the
      cyanoethyl group. After synthesis these ODNs were found to be stable to the
      condition required to remove base labile protecting groups and the ODNs from the
      solid support. Moreover the use of 1-(4,4-dimethyl-2, 6-dioxocyclohex-1-ylidene)
      ethyl (Dde) in place of Z protection on the amino alcohol has allowed us to
      introduce cationic aminoethyl phosphotriester modifications into ODNs. Melting
      temperatures of duplexes containing cationic or hydrophobic Z modified ODNs
      indicate that the backbone-phosphotriester modifications minimally affect duplex
      stability. Nuclease stability assays demonstrate that these phosphotriesters are
      resistant toward 5'- and 3'-exonucleases. Fluorescently labeled 23-mer ODNs
      modified with four cationic or hydrophobic Z phosphotriester linkages show
      efficient cellular uptake during passive transfection in HeLa and Jurkat cells. 

PMID- 26317153
TI  - High levels of RAD51 perturb DNA replication elongation and cause unscheduled
      origin firing due to impaired CHK1 activation.
AB  - In response to replication stress ATR signaling through CHK1 controls the intra-S
      checkpoint and is required for the maintenance of genomic integrity. Homologous
      recombination (HR) comprises a series of interrelated pathways that function in
      the repair of DNA double strand breaks and interstrand crosslinks. In addition,
      HR, with its key player RAD51, provides critical support for the recovery of
      stalled forks during replication. High levels of RAD51 are regularly found in
      various cancers, yet little is known about the effect of the increased RAD51
      expression on intra-S checkpoint signaling. Here, we describe a role for RAD51 in
      driving genomic instability caused by impaired replication and intra-S mediated
      CHK1 signaling by studying an inducible RAD51 overexpression model as well as 10
      breast cancer cell lines. We demonstrate that an excess of RAD51 decreases I-Sce
      I mediated HR despite formation of more RAD51 foci. Cells with high RAD51 levels
      display reduced elongation rates and excessive dormant origin firing during
      undisturbed growth and after damage, likely caused by impaired CHK1 activation.
      In consequence, the inability of cells with a surplus of RAD51 to properly repair
      complex DNA damage and to resolve replication stress leads to higher genomic
      instability and thus drives tumorigenesis. 

PMID- 26317156
TI  - Dimensions of Personality Organization and Sexual Life in a Community Sample of
      Women.
AB  - The aim of this study was to explore the relationship between dimensions of
      borderline personality organization (as assessed according to Kernberg's model),
      sexual dysfunctions, and paraphilic interest in a community sample of women. Two
      hundred and sixty-six healthy women were asked to complete a set of
      questionnaires including the Inventory of Personality Organization (IPO), the
      Italian version of the Female Sexual Function Index, and a checklist to assess
      the prevalence of paraphilic interests. Results showed that women with sexual
      dysfunctions and paraphilic interests are characterized by higher scores on three
      out of four IPO subscales: Instability of self/others, Instability of behavior,
      and Psychosis. The results provide evidence of a possible connection between
      borderline personality organization and sexual life and support the need for a
      thorough assessment of personality functioning in patients with sexual problems. 

PMID- 26317158
TI  - Fabrication and Characterization of Self-Assembled Nanoparticle/Polyelectrolyte
      Multilayer Films.
AB  - The formation of multilayer films of organothiol-stabilized gold nanoparticles
      and polyelectrolyte, synthesized using the "layer-by-layer" technique, has been
      investigated. The formation of such films requires the alternation of surface
      charge with each layer deposited and is thus amenable to study by the Kelvin
      probe technique. The early stages of multilayer film formation have been studied
      using a combination of X-ray photoelectron spectroscopy, spectroscopic
      ellipsometry, and Kelvin probe microscopy. Our results suggest that the
      polyelectrolyte/nanoparticle film can be considered as a wide-band-gap
      semiconductor with a depletion width, at the substrate/film interface, extending
      several nanometers into the film. From our ellipsometry data, we are able to
      provide optical constants for these hybrid organic/inorganic films. 

PMID- 26317157
TI  - Depletion of the cisplatin targeted HMGB-box factor UBF selectively induces p53
      independent apoptotic death in transformed cells.
AB  - Cisplatin-DNA adducts act as strong decoys for the Upstream Binding Factor UBF
      (UBTF) and have been shown to inhibit transcription of the ribosomal RNA genes by
      RNA polymerase I. However, it is unclear if this plays a significant role in the
      chemotherapeutic activity of cis- or carboplatin. We find that cisplatin in fact
      induces a very rapid displacement of UBF from the ribosomal RNA genes and strong
      inhibition of ribosomal RNA synthesis, consistent with this being an important
      factor in its cytotoxicity. Using conditional gene deletion, we recently showed
      that UBF is an essential factor for transcription of the ribosomal RNA genes and
      for ribosome biogenesis. We now show that loss of UBF arrests cell proliferation
      and induces fully penetrant, rapid and synchronous apoptosis, as well as nuclear
      disruption and cell death, specifically in cells subjected to oncogenic stress.
      Apoptosis is not affected by homozygous deletion of the p53 gene and occurs
      equally in cells transformed by SV40 T antigens, by Myc or by a combination of
      Ras & Myc oncogenes. The data strongly argue that inhibition of UBF function is a
      major factor in the cytotoxicity of cisplatin. Hence, drug targeting of UBF may
      be a preferable approach to the use of the highly toxic platins in cancer
      therapy. 

PMID- 26317159
TI  - Mice lacking circadian clock components display different mood-related behaviors
      and do not respond uniformly to chronic lithium treatment.
AB  - Genomic studies suggest an association of circadian clock genes with bipolar
      disorder (BD) and lithium response in humans. Therefore, we tested mice mutant in
      various clock genes before and after lithium treatment in the forced swim test
      (FST), a rodent behavioral test used for evaluation of depressive-like states. We
      find that expression of circadian clock components, including Per2, Cry1 and Rev
      erbalpha, is affected by lithium treatment, and thus, these clock components may
      contribute to the beneficial effects of lithium therapy. In particular, we
      observed that Cry1 is important at specific times of the day to transmit lithium
      mediated effects. Interestingly, the pathways involving Per2 and Cry1, which
      regulate the behavior in the FST and the response to lithium, are distinct as
      evidenced by the phosphorylation of GSK3beta after lithium treatment and the
      modulation of dopamine levels in the striatum. Furthermore, we observed the co
      existence of depressive and mania-like symptoms in Cry1 knock-out mice, which
      resembles the so-called mixed state seen in BD patients. Taken together our
      results strengthen the concept that a defective circadian timing system may
      impact directly or indirectly on mood-related behaviors. 

PMID- 26317160
TI  - Repair of Alkylation Damage in Eukaryotic Chromatin Depends on Searching Ability
      of Alkyladenine DNA Glycosylase.
AB  - Human alkyladenine DNA glycosylase (AAG) initiates the base excision repair
      pathway by excising alkylated and deaminated purine lesions. In vitro biochemical
      experiments demonstrate that AAG uses facilitated diffusion to efficiently search
      DNA to find rare sites of damage and suggest that electrostatic interactions are
      critical to the searching process. However, it remains an open question whether
      DNA searching limits the rate of DNA repair in vivo. We constructed AAG mutants
      with altered searching ability and measured their ability to protect yeast from
      alkylation damage in order to address this question. Each of the conserved
      arginine and lysine residues that are near the DNA binding interface were
      mutated, and the functional impacts were evaluated using kinetic and
      thermodynamic analysis. These mutations do not perturb catalysis of N-glycosidic
      bond cleavage, but they decrease the ability to capture rare lesion sites.
      Nonspecific and specific DNA binding properties are closely correlated,
      suggesting that the electrostatic interactions observed in the specific
      recognition complex are similarly important for DNA searching complexes. The
      ability of the mutant proteins to complement repair-deficient yeast cells is
      positively correlated with the ability of the proteins to search DNA in vitro,
      suggesting that cellular resistance to DNA alkylation is governed by the ability
      to find and efficiently capture cytotoxic lesions. It appears that chromosomal
      access is not restricted and toxic sites of alkylation damage are readily
      accessible to a searching protein. 

PMID- 26317161
TI  - The Importance of Acoustic Temporal Fine Structure Cues in Different Spectral
      Regions for Mandarin Sentence Recognition.
AB  - OBJECTIVES: To study the relative contribution of acoustic temporal fine
      structure (TFS) cues in low-, mid-, and high-frequency regions to Mandarin
      sentence recognition. DESIGN: Twenty-one subjects with normal hearing were
      involved in a study of Mandarin sentence recognition using acoustic TFS. The
      acoustic TFS information was extracted from 10 3-equivalent rectangular bandwidth
      wide bands within the range 80 to 8858 Hz using the Hilbert transform and was
      assigned to low-, mid-, and high-frequency regions. Percent-correct recognition
      scores were obtained with acoustic TFS information presented using one, two, or
      three frequency regions. The relative weights of the three frequency regions were
      calculated using the least-squares approach. RESULTS: Results indicated that the
      mean percent-correct scores for sentence recognition using acoustic TFS were
      nearly perfect for stimuli with all three frequency regions together. Recognition
      was approximately 50 to 60% correct with only the low- or mid-frequency region
      but decreased to approximately 5% correct with only the high-frequency region of
      acoustic TFS. The mean weights of the low-, mid-, and high-frequency regions were
      0.39, 0.48, and 0.13, respectively, and the difference between each pair of
      frequency regions was statistically significant. CONCLUSION: The acoustic TFS
      cues in low- and mid-frequency regions convey greater information for Mandarin
      sentence recognition, whereas those in the high-frequency region have little
      effect.

PMID- 26317162
TI  - Predicting Speech-in-Noise Recognition From Performance on the Trail Making Test:
      Results From a Large-Scale Internet Study.
AB  - OBJECTIVE: The aim of the study was to investigate the utility of an internet
      based version of the trail making test (TMT) to predict performance on a speech
      in-noise perception task. DESIGN: Data were taken from a sample of 1509 listeners
      between ages 18 and 91 years old. Participants completed computerized versions of
      the TMT and an adaptive speech-in-noise recognition test. All testing was
      conducted via the internet. RESULTS: The results indicate that better performance
      on both the simple and complex subtests of the TMT are associated with better
      speech-in-noise recognition scores. Thirty-eight percent of the participants had
      scores on the speech-in-noise test that indicated the presence of a hearing loss.
      CONCLUSIONS: The findings suggest that the TMT may be a useful tool in the
      assessment, and possibly the treatment, of speech-recognition difficulties. The
      results indicate that the relation between speech-in-noise recognition and TMT
      performance relates both to the capacity of the TMT to index processing speed and
      to the more complex cognitive abilities also implicated in TMT performance.

PMID- 26317163
TI  - Duodenal Obstruction Caused by Acute Appendicitis with Intestinal Malrotation in
      a Child.
AB  - BACKGROUND: In patients with intestinal malrotation, the diagnosis of acute
      appendicitis can be difficult due to atypical presentation. Duodenal obstruction
      caused by acute appendicitis with the presence of malrotation has rarely been
      reported in children. CASE REPORT: We report the case of a 14-year-old male
      patient with bilious vomiting and abdominal distension. A diagnosis could not be
      made by computed tomography, ultrasonography, or endoscopy. We observed a dilated
      stomach and malrotation in laparotomy. The caecum was in the right upper
      quadrant, and an inflamed appendix was located in the subhepatic region. After
      the appendectomy, the cecum was mobilized and fixed in the right lower quadrant.
      CONCLUSIONS: In children with intestinal malrotation, acute appendicitis can
      present as duodenal obstruction without abdominal pain, and standard imaging
      methods can miss the correct diagnosis.

PMID- 26317165
TI  - Left-sided Noninvasive Vagus Nerve Stimulation Suppresses Atrial Fibrillation by
      Upregulating Atrial Gap Junctions in Canines.
AB  - BACKGROUND: We have previously shown that right-sided low-level tragus nerve
      stimulation (LL-TS) is an effective approach for the treatment of atrial
      fibrillation (AF) induced by rapid atrial pacing (RAP) and acts by preventing the
      loss of atrial connexins (Cxs). Whether a left-sided approach would achieve the
      same effect remains unknown. OBJECTIVE: We hypothesized that left-sided LL-TS
      would inhibit AF by preserving atrial Cxs as effectively as right-sided LL-TS.
      METHODS: Bilateral thoracotomies allowed the attachment of multielectrode
      catheters to the pulmonary vein and non-pulmonary vein sites in 32 anaesthetized
      beagles. The dogs were randomly divided into 3 groups: RAP group (9 hours of RAP
      at the left appendage, n = 10), LL-TS group (9-hour RAP plus LL-TS, n = 12), and
      control group (sham RAP without LL-TS, n = 10). Alligator clips were clipped on
      the tragus of the left ear for electrical stimulation (20 Hz, 1 millisecond
      square waves). A voltage of stimulation setting at 80% below the threshold that
      slowed the sinus rate was defined as LL-TS. Electrophysiological parameters were
      measured at baseline and 9 hours after pacing. Connexin proteins from atrial
      tissues were measured at the end of the protocol. RESULTS: RAP induced a
      significant reduction in the effective refractory period and an increase in AF
      inducibility (P < 0.05). However, left-sided LL-TS reversed the effective
      refractory period reduction induced by RAP and the increase in AF inducibility.
      It also shortened the AF duration and prolonged the AF cycle length, which are
      associated with Cx40 and Cx43 upregulation (P < 0.05). CONCLUSIONS: We propose
      that left-sided LL-TS exerts its anti-AF effects through upregulation of Cxs as
      effectively as right-sided LL-TS, suggesting that LL-TS for AF suppression is not
      unique to the right tragus nerve.

PMID- 26317166
TI  - Nifekalant Hydrochloride and Amiodarone Hydrochloride Result in Similar
      Improvements for 24-Hour Survival in Cardiopulmonary Arrest Patients: The SOS
      KANTO 2012 Study.
AB  - BACKGROUND: Amiodarone (AMD), nifekalant (NIF), and lidocaine (LID)
      hydrochlorides are widely used for ventricular tachycardia/fibrillation (VT/VF).
      This study retrospectively investigated the NIF potency and the differential
      effects of 2 initial AMD doses (<=150 mg or 300 mg) in the Japanese SOS-KANTO
      2012 study population. METHODS AND RESULTS: From 16,164 out-of-hospital cardiac
      arrest cases, 500 adult patients using a single antiarrhythmic drug for shock
      resistant VT/VF were enrolled and categorized into 4 groups (73 LID, 47 NIF, 173
      AMD-<=150, and 207 AMD-300). Multivariate analyses evaluated the outcomes of NIF,
      AMD-<=150, or AMD-300 groups versus LID group. Odds ratios (ORs) for survival to
      admission were 3.21 [95% confidence interval (CI): 1.38-7.44, P < 0.01] in NIF
      and 3.09 (95% CI: 1.55-6.16, P < 0.01) in AMD-<=150 groups and significantly
      higher than those of the LID group. However, the OR was 1.78 (95% CI: 0.90-3.51,
      P = 0.10) in AMD-300 group and was not significant than LID group. ORs for 24
      hour survival were 6.68 in NIF, 4.86 in AMD-<=150, and 2.97 in AMD-300, being
      significantly higher in these groups. CONCLUSIONS: NIF and AMD result in similar
      improvements for 24-hour survival in cardiopulmonary arrest patients, and this
      suggest the necessity of a randomized control study.

PMID- 26317168
TI  - Low numbers of tryptase+ and chymase+ mast cells associated with reduced survival
      and advanced tumor stage in melanoma.
AB  - The role of mast cells in cutaneous melanoma remains unclear. Tryptase and
      chymase are serine proteinases and major proteins in mast cell secretory
      granules. Therefore, this study aimed to investigate the presence of tryptase and
      chymase mast cells in benign and malignant cutaneous melanocytic lesions and in
      lymph node metastases of melanomas. The presence of positively stained mast cells
      was correlated with clinicopathological characteristics in invasive melanomas.
      Paraffin-embedded sections of 28 benign (13 intradermal, 10 compound, and five
      junctional nevi) and 26 dysplastic nevi, 15 in-situ melanomas, 36 superficially
      (pT1, Breslow's thickness<1 mm), and 49 deeply (pT4, Breslow's thickness>4 mm)
      invasive melanomas and 30 lymph node metastases were immunohistochemically
      stained for mast cell tryptase and chymase, and immunopositive cells were counted
      using the hotspot counting method. The mean count of tryptase and chymase mast
      cells was lower in invasive melanomas compared with in-situ melanomas and
      dysplastic and benign nevi. In deeply invasive melanomas, the difference was
      statistically significant compared with dysplastic nevi (P=0.003 for tryptase and
      P=0.009 for chymase) and in-situ melanomas (0.043 for tryptase). Low numbers of
      tryptase mast cells were associated with poor overall survival (P=0.031) in
      deeply invasive melanomas and with a more advanced stage (T1b, P=0.008) in
      superficially invasive melanomas. Low numbers of chymase mast cells were
      associated with microsatellites (P=0.017) in deeply invasive melanomas. The
      results suggest that these serine proteinases of mast cells may be protective in
      the pathogenesis of melanoma. 

PMID- 26317169
TI  - The HGF-cMET signaling pathway in conferring stromal-induced BRAF-inhibitor
      resistance in melanoma.
AB  - Genetic heterogeneity in melanoma is well established. Given this, as well as the
      complexity of mechanisms involved in cancer in vivo, a more complete
      understanding of the development of resistance requires a closer look at the
      tumor ecosystem, including the microenvironment. Echoing this more comprehensive
      approach, a number of recent studies on BRAF-inhibitor resistance have brought
      our attention back to the tumor microenvironment, particularly through a focus on
      HGF-cMET signaling - a known means of stromal-parenchymal communication. Our
      review focuses on the results of these recent investigations, and through a
      review of relevant HGF-cMET past literature looks to provide a context by which
      to better understand the role of stromal-parenchymal signaling in BRAF
      resistance/melanoma progression. 

PMID- 26317167
TI  - Risk Factors for Type 1 Diabetes Recurrence in Immunosuppressed Recipients of
      Simultaneous Pancreas-Kidney Transplants.
AB  - Patients with type 1 diabetes (T1D) who are recipients of pancreas transplants
      are believed to rarely develop T1D recurrence in the allograft if effectively
      immunosuppressed. We evaluated a cohort of 223 recipients of simultaneous
      pancreas-kidney allografts for T1D recurrence and its risk factors. With long
      term follow-up, recurrence was observed in approximately 7% of patients.
      Comparing the therapeutic regimens employed in this cohort over time, lack of
      induction therapy was associated with recurrence, but this occurs even with the
      current regimen, which includes induction; there was no influence of maintenance
      regimens. Longitudinal testing for T1D-associated autoantibodies identified
      autoantibody positivity, number of autoantibodies, and autoantibody conversion
      after transplantation as critical risk factors. Autoantibodies to the zinc
      transporter 8 had the strongest and closest temporal association with recurrence,
      which was not explained by genetically encoded amino acid sequence donor
      recipient mismatches for this autoantigen. Genetic risk factors included the
      presence of the T1D-predisposing HLA-DR3/DR4 genotype in the recipient and donor
      recipient sharing of HLA-DR alleles, especially HLA-DR3. Thus, T1D recurrence is
      not uncommon and is developing in patients treated with current
      immunosuppression. The risk factors identified in this study can be assessed in
      the transplant clinic to identify recurrent T1D and may lead to therapeutic
      advances. 

PMID- 26317170
TI  - Microphthalmia transcription factor in malignant melanoma predicts occult
      sentinel lymph node metastases and survival.
AB  - Microphthalmia transcription factor (Mitf) is involved in melanocyte development
      and differentiation. We previously reported that Mitf expression, as detected by
      immunohistochemical analysis, is an independent prognostic marker in patients
      with intermediate-thickness melanoma. However, the clinical significance of Mitf
      expression in melanoma is not well delineated. In this prospective study, we
      attempted to demonstrate the correlation between Mitf expression in primary
      melanoma and the sentinel lymph node status and prognosis. We prospectively
      examined primary cutaneous melanomas from 94 patients undergoing nodal staging by
      sentinel lymph node biopsy. We quantified the percentage of tumor cells whose
      nuclei stained with the Mitf antibody visually. Survival curves were generated
      using the Kaplan-Meier method. The correlation between Mitf expression and nodal
      status was evaluated using the Mann-Whitney U-test. Here we demonstrate that Mitf
      expression is directly correlated with both disease-free survival (DFS) and
      overall survival (OS) over a median follow-up of 28.5 months. The mean DFS and OS
      in the eight patients whose melanomas did not stain positive for Mitf were
      15.75+/-3.36 months (median, 12 months) and 38.17+/-5.18 months (median, 29
      months), respectively. These results are significantly lower than those for
      patients who showed evidence of Mitf expression, in whom the mean DFS and OS were
      66.1+/-4.03 months (median, not reached, P=0.0001) and 66.75+/-38.17 months
      (median, not reached, P=0.0001), respectively. The mean DFS and OS with greater
      than 25% (67 patients) of the melanoma cells staining positive for Mitf
      expression were 78.37+/-2.78 and 82.38+/-1.6 months, respectively, compared with
      26.37+/-3.2 months (P=0.0001) and 44.53+/-4.5 months (P=0.0001), respectively,
      with up to 25% (27 patients) of cells stained positive for Mitf expression. In
      addition, there was a significant relationship between Mitf expression and nodal
      status, as evaluated by sentinel node biopsy. For example, none of the melanomas
      with greater than 50% Mitf expression had a positive sentinel node biopsy. Our
      study shows that expression of the molecular marker Mitf in primary cutaneous
      melanomas is a useful tool in assessing lymph node status. Mitf immunostaining in
      the primary tumor serves as a reliable predictor of occult lymph node metastases,
      as well as a favorable prognosticator of DFS and OS in melanoma patients. 

PMID- 26317172
TI  - Copper-chiral camphor beta-amino alcohol complex catalyzed asymmetric Henry
      reaction.
AB  - Four novel chiral amino alcohols were synthesized from D-(+)-camphor and utilized
      as ligands in a Cu(I)-catalyzed asymmetric Henry reaction. The reactions were
      carried out under mild conditions with excellent enantioselectivities and
      moderate yields without the exclusion of air or moisture. The highest
      enantioselectivity was observed up to 94% enantiomeric excess (ee) with ligand in
      toluene at room temperature.

PMID- 26317171
TI  - Inhibition of Notch3 prevents monocrotaline-induced pulmonary arterial
      hypertension.
AB  - It has been shown that activation of Notch3 signaling is involved in the
      development of pulmonary arterial hypertension (PAH) by stimulating pulmonary
      arteries remodeling, while the molecular mechanisms underlying this are still
      largely unknown. The aims of this study are to address these issues.
      Monocrotaline dramatically increased right ventricle systolic pressure to 39.0 +/
      2.6 mmHg and right ventricle hypertrophy index to 53.4 +/- 5.3% (P < 0.05 versus
      control) in rats, these were accompanied with significantly increased
      proliferation and reduced apoptosis of pulmonary vascular cells as well as
      pulmonary arteries remodeling. Treatment of PAH model with specific Notch
      inhibitor DAPT significantly reduced right ventricle systolic pressure to 26.6 +/
      1.3 mmHg and right ventricle hypertrophy index to 33.5 +/- 2.6% (P < 0.05 versus
      PAH), suppressed proliferation and enhanced apoptosis of pulmonary vascular cells
      as well as inhibited pulmonary arteries remodeling. Our results further indicated
      that level of Notch3 protein and NICD3 were increased in MCT-induced model of
      PAH, this was accompanied with elevation of Skp2 and Hes1 protein level and
      reduction of P27Kip1. Administration of rats with DAPT-prevented MCT induced
      these changes. Our results suggest that Notch3 signaling activation stimulated
      pulmonary vascular cells proliferation by Skp2-and Hes1-mediated P27Kip1
      reduction, and Notch3 might be a new target to treat PAH. 

PMID- 26317173
TI  - Biomedical Activity and Related Volatile Compounds of Thai Honeys from 3
      Different Honeybee Species.
AB  - This study investigated the effect of 3 factors (floral source, honeybee species,
      and postcollection processing) that influence the antibacterial activity, free
      radical reduction, and other biochemical compositions of different honey types
      typical of Thailand. Honey samples from 3 honeybee species (Apis mellifera, Apis
      cerana, and Apis dorsata) were obtained from 9 floral sources (longan, wild
      flower, lychee, coffee, sunflower, sesame, bitter bush, para-rubber, and manuka
      as a control) in different regions of Thailand. These samples were evaluated for
      both their total and nonperoxide antibacterial activity against 10 human
      pathogens by agar incorporation technique. Honey samples were further analyzed to
      evaluate the capacity for free radical-scavenging activity, total phenolic
      content, and the total flavonoid contents by the 2,2-diphenyl-1-picrylhydrazyl
      assay, Folin-Ciocalteu method, and aluminum chloride colorimetric assay,
      respectively. Furthermore, the volatile organic compounds (VOCs) of Thai honey
      samples were investigated by headspace solid-phase microextraction and gas
      chromatography-mass spectrometry analysis. Findings of this study suggest a
      strong correlation between floral origin and honeybee species on one hand, and
      differences in %Brix, total acidity, protein content, antimicrobial activities,
      free radical reduction, phenolic, and flavonoid contents on the other hand.
      Moreover, VOCs of wild and coffee honey types were remarkably different,
      depending on the floral source. Both honeys contained characteristics of VOCs,
      some of which are involved in antibacterial and antioxidant activities. PRACTICAL
      APPLICATION: Different origins and processing (floral source, honeybee species,
      and postcollection processing) of Thai honeys result in different antibacterial
      activities, physico-chemical properties, and aroma. Based on these findings,
      consumers of honey could select the type of honey based on their needs and
      preferred aroma.

PMID- 26317174
TI  - Risk Factors for Venous Thromboembolism Among Reproductive Age Women.
AB  - BACKGROUND: Venous thromboembolism (VTE) is rare among young women and is often
      presumed to occur in the setting of a genetic predisposition or during the use of
      estrogen-containing combined hormonal contraceptive or to have an unknown cause.
      This study aims to describe the distribution of VTE risk factors among women with
      a confirmed VTE. METHODS: We identified all women aged 15-46 years with a VTE
      diagnosis at Columbia University Medical Center from 2005 to 2012 using medical
      center databases. We then reviewed all electronic medical records to validate the
      diagnoses and identify risk factors associated with each confirmed case. RESULTS:
      We identified 315 cases and confirmed 186 (59%). The proportion of unconfirmed
      cases increased over time. Forty percent of confirmed cases were associated with
      hormonal contraceptives or pregnancy. Ninety-five percent of confirmed cases had
      identifiable major risk factors including a personal history, family history,
      malignancy or other predisposing illness, recent long-haul travel, trauma,
      hospitalization, and obesity; many had multiple simultaneous risk factors. None
      of the confirmed cases was associated with a previously known genetic
      predisposition, but in 10 confirmed cases a genetic predisposition was identified
      during evaluation. In only 10 of the 186 confirmed cases could we not identify
      any acquired risk factor, and only 2 of those 10 women had a genetic
      predisposition. CONCLUSIONS: Many reproductive age women experiencing a VTE have
      risk factors unique to this group, and most have multiple risk factors,
      confirming that this is a multifactorial disease. The large proportion of
      unconfirmed cases suggests the need for great caution in using administrative
      databases for research due to poor diagnostic specificity and due to lack of
      information about additional risk factors.

PMID- 26317175
TI  - Fluorescence- and bioluminescence-based approaches to study GPCR ligand binding.
AB  - Ligand binding is a vital component of any pharmacologist's toolbox and allows
      the detailed investigation of how a molecule binds to its receptor. These studies
      enable the experimental determination of binding affinity of labelled and
      unlabelled compounds through kinetic, saturation (Kd ) and competition (Ki )
      binding assays. Traditionally, these studies have used molecules labelled with
      radioisotopes; however, more recently, fluorescent ligands have been developed
      for this purpose. This review will briefly cover receptor ligand binding theory
      and then discuss the use of fluorescent ligands with some of the different
      technologies currently employed to examine ligand binding. Fluorescent ligands
      can be used for direct measurement of receptor-associated fluorescence using
      confocal microscopy and flow cytometry as well as in assays such as fluorescence
      polarization, where ligand binding is monitored by changes in the free rotation
      when a fluorescent ligand is bound to a receptor. Additionally, fluorescent
      ligands can act as donors or acceptors for fluorescence resonance energy transfer
      (FRET) with the development of assays based on FRET and time-resolved FRET (TR
      FRET). Finally, we have recently developed a novel bioluminescence resonance
      energy transfer (BRET) ligand binding assay utilizing a small (19 kDa), super
      bright luciferase subunit (NanoLuc) from a deep sea shrimp. In combination with
      fluorescent ligands, measurement of RET now provides an array of methodologies to
      study ligand binding. While each method has its own advantages and drawbacks,
      binding studies using fluorescent ligands are now a viable alternative to the use
      of radioligands. Linked Articles This article is part of a themed section on
      Molecular Pharmacology of G Protein-Coupled Receptors. To view the other articles
      in this section visit
      http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.20/issuetoc.

PMID- 26317177
TI  - Auscultate, palpate and tap: time to re-evaluate.
AB  - AIM: To determine the accuracy of current methods of heart rate (HR) assessment.
      METHODS: All participants palpated a simulated pulsating umbilicus (UMB),
      listened to a tapping rate (TAP) and auscultated a simulated HR (AUSC). A
      simulated HR of 54, 88 and 128 beats per minute (bpm) was randomised for all
      methods. RESULTS: Twenty-nine healthcare staff participated in this study.
      Correct assessment of HR of 54 bpm as being within the 0-59 range occurred in
      17.2% UMB, 17.2% TAP and 31% AUSC and was obtained in <10 seconds by 48.3%, 65.5%
      and 62.1%, respectively. A rate of 88 bpm was correctly assessed as within the 60
      100 range in 82.8% UMB, 79.3% TAP and 79.3% AUSC and was obtained in <10 seconds
      by 55.2%, 58.6% and 55.2%, respectively. A rate of 128 bpm was identified as >100
      bpm by 96.6% UMB, 93.1% TAP, and 93.1% AUSC and was obtained in <10 seconds by
      51.7%, 55.2% and 62.1%, respectively. CONCLUSION: Current methods in assessing
      rates below 60 bpm are inaccurate and may overestimate HR. We recommend that
      these methods alone should not be relied upon in neonatal resuscitation and
      objective assessment of heart rate should be readily available at all newborn
      resuscitations.

PMID- 26317180
TI  - Posterolateral fusion in acute traumatic thoracolumbar fractures: a comparison of
      demineralized bone matrix and autologous bone graft.
AB  - INTRODUCTION Alternative fusion expanders are in clinical use for instrumented
      posterolateral fusion (PLF) to avoid donor site morbidity in autologous bone
      graft (ABG) harvesting. Purpose of this study was to evaluate demineralized bone
      matrix (DBM) in PLF as alternative to the gold standard of ABG in acute traumatic
      vertebral body fractures of the thoracolumbar spine. MATERIAL AND METHODS We
      retrospectively identified 101 patients with acute traumatic vertebral body
      fractures of the thoracic and lumbar spine who were treated with instrumented PLF
      in our level one trauma center between 2005 and 2011. Patients with a primary
      paraplegia, osteodepriving disease or loss to follow-up had been excluded. Until
      August 2008, autologous bone graft harvested from the posterior iliac crest was
      used in PLF (control group n = 46). Starting September 2008, DBM was used as
      fusion expander in PLF (study group n = 16). Clinical and radiological evaluation
      was performed with a minimum followup of 18 months to assess the clinical and
      radiological outcome. RESULTS We found a fusion rate of 94% in patients
      undergoing PLF with the use of DBM and 100% with the use of ABG. There was one
      major complication of deep infection in the DBM group and two cases of
      superficial wound infection in the ABG group. We discovered a trend of reduced
      operating time with the use of DBM. CONCLUSIONS DBM leads to a similar fusion
      rate as the use of ABG in patients undergoing PLF for acute traumatic vertebral
      body fractures of the thoracic and lumbar spine. DBM is associated with reduced
      operating time. LEVEL OF EVIDENCE III: case-control study Key words:
      demineralized bone matrix instrumented posterolateral fusion, acute traumatic
      vertebral body fracture, thoracolumbar spine, autologous bone graft.

PMID- 26317176
TI  - Evaluating the Effects of Varenicline on Craving, Withdrawal, and Affect in a
      Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Varenicline for
      Smokeless Tobacco Dependence in India.
AB  - This study examined changes in tobacco craving, withdrawal, and affect as
      correlates of efficacy in a phase-2 clinical trial of varenicline for smokeless
      tobacco dependence in India. Smokeless tobacco users (N = 237) at the All India
      Institute of Medical Sciences were randomized to placebo or varenicline.
      Abstinence was defined as cotinine-verified seven-day point prevalence cessation
      at end of treatment (EOT). General Linear Model repeated measures assessed the
      effects of treatment condition, time, abstinence state, and interaction effects
      on changes in craving, withdrawal, positive (PA) and negative affect (NA) from
      baseline to EOT. All participants showed a significant reduction in withdrawal (p
      < .001), total craving (p < .001), positive reinforcement (PR) craving (p <
      .001), and NA (p = .02), and an increase in PA (p = .04) from baseline to EOT.
      However, there were no differences between placebo and varenicline participants
      in measures of withdrawal, craving, or affect from baseline to week 3 or at EOT.
      Significant interactions between time and abstinence state were found for total
      craving (p = .008), PR craving (p < .001), and withdrawal (p = .001), indicating
      reductions in these processes among those abstinent vs. those still chewing
      smokeless tobacco. Additional research is needed concerning the effects of
      varenicline on craving, withdrawal, and affect among smokeless tobacco users. 

PMID- 26317178
TI  - Methanethiol Binding Strengths and Deprotonation Energies in Zn(II)-Imidazole
      Complexes from M05-2X and MP2 Theories: Coordination Number and Geometry
      Influences Relevant to Zinc Enzymes.
AB  - Zn(II) is used in nature as a biocatalyst in hundreds of enzymes, and the
      structure and dynamics of its catalytic activity are subjects of considerable
      interest. Many of the Zn(II)-based enzymes are classified as hydrolytic enzymes,
      in which the Lewis acidic Zn(II) center facilitates proton transfer(s) to a Lewis
      base, from proton donors such as water or thiol. This report presents the results
      of a quantum computational study quantifying the dynamic relationship between the
      zinc coordination number (CN), its coordination geometry, and the thermodynamic
      driving force behind these proton transfers originating from a charge-neutral
      methylthiol ligand. Specifically, density functional theory (DFT) and second
      order perturbation theory (MP2) calculations have been performed on a series of
      [(imidazole)nZn-S(H)CH3](2+) and [(imidazole)nZn-SCH3](+) complexes with the CN
      varied from 1 to 6, n = 0-5. As the number of imidazole ligands coordinated to
      zinc increases, the S-H proton dissociation energy also increases, (i.e., 
      S(H)CH3 becomes less acidic), and the Zn-S bond energy decreases. Furthermore, at
      a constant CN, the S-H proton dissociation energy decreases as the S-Zn-(ImH)n
      angles increase about their equilibrium position. The zinc-coordinated thiol can
      become more or less acidic depending upon the position of the coordinated
      imidazole ligands. The bonding and thermodynamic relationships discussed may
      apply to larger systems that utilize the [(His)3Zn(II)-L] complex as the
      catalytic site, including carbonic anhydrase, carboxypeptidase, beta-lactamase,
      the tumor necrosis factor-alpha-converting enzyme, and the matrix
      metalloproteinases. 

PMID- 26317181
TI  - Fragility fractures of the pelvis: should they be fixed?
AB  - Due to the aging population, there is an increasing number of fragility fractures
      of the pelvis (FFP). They are the result of low energy trauma. The bone breaks
      but the ligaments remain intact. Immobilizing pain at the pubic region or at the
      sacrum is the main symptom. Conventional radiographs reveal pubic rami fractures,
      but lesions of the dorsal pelvis are hardly visible and easily overlooked. CT of
      the pelvis with multiplanar reconstructions show the real extension of the
      lesion. Most patients have a history of osteoporosis or other fragility
      fractures. The new classification distinguishes between four categories of
      different and increasing instability. FFP Type I are anterior lesions only, FFP
      Type II are non-displaced posterior lesions, FFP Type III are displaced
      unilateral posterior lesions and FFP Type IV are displaced bilateral posterior
      lesions. Subgroups discriminate between the localization of the dorsal
      instability. FFP Type I lesions are treated non-operatively. FFP Type II lesions
      are fixed in a percutaneous procedure when a trial of conservative treatment was
      not successful. FFP Type III lesions are treated with open reduction and internal
      fixation (ORIF). FFP Type IV lesions are treated with bilateral ORIF or with a
      bridging osteosynthesis. Iliosacral screw osteosynthesis is widely used, but has
      an elevated risk of screw loosening due to diminished bine mineral density.
      Transsacral bar osteosynthesis enable interfragmentary compression and does not
      have this danger of loosening. Bridging plate osteosynthesis is used as an
      additional fixation to iliosacral screw osteosynthesis. Lumbopelvic fixation is
      restricted to highly unstable lumbopelvic dissociations. More studies are needed
      to find the optimal treatment for each type of instability. Key words: pelvis,
      fragility fracture, diagnosis, classification, treatment. 

PMID- 26317182
TI  - Quality of life and functional outcome of periprosthetic fractures around the
      knee following knee arthroplasty.
AB  - PURPOSE OF THE STUDY The present study aimed to analyse both, the functional
      outcome and quality of life after surgical treatment of periprosthetic fractures
      following TKA. MATERIAL AND METHODS A retrospective review of all periprosthetic
      fractures following knee arthroplasty which have been surgically treated at our
      institution between January 2005 and January 2012 was conducted. Beside
      epidemiologic data, type of surgery and postoperative complications were
      recorded. The functional outcome was assessed using range of motion, Knee Society
      Score and VAS to evaluate pain. Quality of life was evaluated using SF-36 and
      WOMAC. Furthermore patients mobility and comorbidities were analysed. RESULTS 25
      (mean age 76 +/- 8 years; m:w 5:20) patients were included. The overall
      complication rate was 24%. Mean KSS knee score was 73 +/- 19 and a function score
      was 41 +/- 36. Range of motion revealed 95 degrees  +/- 24 degrees  (active) and
      98 degrees  +/- 16 degrees  (passive). The total SF-36 scored a mean of 41 +/- 6
      and 29 +/- 19 in average considering the WOMAC index (pain: 19 +/- 20; stiffness:
      23 +/- 27; daily: 47 +/- 29). 20% were able to mobilise without help as opposed
      to 80% that were in need for assistance. Our analysis revealed no influence of
      the final outcome as a function of fracture type or type of treatment. Multiple
      regression analysis could not reveal significant influence of the comorbidities.
      CONCLUSION Periprosthetic fractures following knee arthroplasty are accompanied
      by a significant decrease of the knee function and quality of life as well as
      high complication rates. Since patient's quality of life apparently depends on
      the functional outcome, future efforts should aim to improve these parameters.
      Key words: periprosthetic fracture, total knee arthroplasty, quality of life,
      functional outcome, locking plate. 

PMID- 26317183
TI  - [Validity of the Morawietz classification for evaluation of periprosthetic
      tissue].
AB  - PURPOSE OF THE STUDY A consensual classification of the periprosthetic interface
      membrane obtained at revision total joint arthroplasty was published by Morawietz
      et al. in 2006. Based on histomorphological criteria, four types of
      periprosthetic membrane were proposed: type I, aseptic failure; type II, septic
      failure; type III, combined type (carrying signs of both type I and II); and type
      IV, indeterminate type. The aim of this study was to find out whether and to what
      extent the Morawietz system would be suitable for use at an independent
      institution involved in the evaluation of periprosthetic membranes for a long
      time. Should it appear that the institution achieved an equally good or even
      better agreement between the clinical diagnosis and the histopathological
      finding, this consensus classification could be recommended for routine use.
      MATERIAL AND METHODS The samples of periprosthetic tissue evaluated in this study
      were obtained during surgery from the following groups of patients: 66 patients
      with aseptic loosening of total hip (THA) or knee arthroplasty, 15 patients with
      infection of THA, 16 patients with THA without any signs of aseptic loosening,
      osteolysis or infection; 8 patients with hip osteoarthritis and 8 patients with
      knee osteoarthritis. Sample collection and processing (for purposes of
      histomorphological evaluation and immunohistochemical staining) was performed
      according to the established protocol. The tissue samples evaluation was made by
      an experienced pathologist hand in hand with the method described in the original
      paper by Morawietz et al. For a more detailed tissue analysis, selected
      antibodies (CD4, CD8, CD20, IFN-gamma and Hsp-60) were visualized by
      immunohistochemistry. RESULTS The majority of samples from aseptic reoperations
      were classified as membranes of the type I (79%) and III (16%). Specimens
      retrieved from septic cases were mostly classified as membranes of type II and
      III (60% together). The septic membranes showed a significantly higher expression
      of CD20 protein when compared with both the aseptic (p < 0.0001) and control THA
      samples (p = 0.003). The membranes retrieved from the surroundings of a stable
      THA without osteolysis and infection had lower expression levels of Hsp60 and IFN
      gamma, when compared with those from both aseptic and septic loosening. Finally,
      Hsp-60 expression was significantly higher in osteoarthritic tissue than in
      samples from stable THA (p = 0.041). DISCUSSION Morawietz et al. proposed a
      standardized classification system for evaluation of periprosthetic tissue. As
      any attempt at generalization of a complex issue, this proposal has certain
      shortcomings. One of these is poor detection of chronic and low-grade infections.
      A method that would improve the conventional counting of polymorphonuclear
      leukocytes is still being sought. In this connection, immunostaining for CD20
      combined with an assessment of antimicrobial peptides may be a promising option.
      The supplementary specimen staining showed that pseudosynovial tissue is much
      more active in patients carrying infection and the least active in samples from
      stable THA in which certain tolerance and thus tissue homeostasis might be
      expected. CONCLUSIONS 1. In this study the distribution of findings classified
      according to the Morawietz system was similar to the results published in the
      original study from 2006. 2. The definition of an aseptic membrane (type I) in
      the Morawietz system meets the requirements of clinical practice (agreement,
      about 80%). 3. An increased sensitivity for infectious membrane detection can be
      achieved by using supplementary immunohistochemical staining effective
      particularly in chronic and low-grade infections. 4. Painless and stable THAs
      typically have very low expression levels of CD4, CD20 and Hsp-60 proteins, and
      interferon- -gamma (IFN-gamma) as well. Key words: total hip arthroplasty, total
      knee arthroplasty, aseptic loosening, prosthetic joint infection, tissue
      analysis, membranes, CD receptors, Hsp-60 protein, IFN-gamma. 

PMID- 26317184
TI  - [The effect of platelet-rich plasma on graft healing in reconstruction of the
      anterior cruciate ligament of the knee joint: prospective study].
AB  - PURPOSE OF THE STUDY Growth factors produced by platelets enhance tissue healing.
      The aim of this study was to confirm or disprove the hypothesis that, in anterior
      cruciate ligament (ACL) reconstruction, the application of platelet-rich plasma
      (PRP) into the tibial and femoral tunnels and in the graft enhances graft
      maturation and graft-bone interface healing and thus improves knee function at 3
      and 12 months post-operatively in comparison with the control group. MATERIAL AND
      METHODS A total of 40 patient had the surgery; 20 underwent single-bundle
      hamstring reconstruction with PRP application (PRP group) and 20 had the same
      surgery without PRP addition (control group). A 5 ml amount of PRP was obtained
      from the patient's peripheral blood. A graft inserted in the bone tunnels was
      fixed with interference screws and, after intra-articular fluid aspiration, 1 ml
      of PRP was injected into each tunnel and 3 ml were evenly applied to the intra
      articular portion of the graft. The patients were examined by MRI at 3 and 12
      months after surgery. The subsidence of swelling in the tunnelsurrounding tissues
      was taken as a sign of graft-bone interface healing, and increased signal
      intensity of the graft was considered as a result of its ligamentisation. The
      knee functional status was evaluated at 3 and 12 post-operative months, using the
      scoring systems (Cincinnati score, IKDC score). RESULTS Bone swelling was found
      at 3 post-operative months in 18 of 20 patients in both the PRP and the control
      group. Graft signal intensity was increased in most patients (19 of the PRP
      group; 18 control patients; p = 0.949). The Cincinnati score at 3 months had an
      average value of 72.7 (34-100; SO, 18.7) in the PRP group and 73.4 (42-99; SO,
      16.3) in the control group (p = 0.793). The functional score after 12 months
      improved to 97.5 (75-100; SO, 12.8) in the PRP group and to 95.1 (66-100; SO,
      13.1) in the control group; there was no significant difference between the
      groups (p = 0.885) at either 3 or 12 months. The IKDC score showed similar
      results. At 12 months bone swelling was recorded in seven out of 20 patients in
      the PRP group and in nine patients in the control group (p = 0.751). Graft signal
      intensity was increased in three and four patients of the PRP and control groups,
      respectively (p = 0.681). There was a statistical difference between the findings
      at 3 and 12 months within each group, but no difference between the groups.
      DISCUSSION In ACL reconstruction, the process of tendon graft-to-bone healing has
      several stages involving inflammation, cell proliferation and graft
      ligamentisation. At each stage, an important role is played by growth factors
      produced by thrombocytes, and therefore their potential use in the treatment of
      injuries to ligaments and tendons has recently come into focus. A number of
      experimental studies dealing with the effect of platelet-rich plasma on soft
      tissue healing has been published. Therefore, the method of using PRP to enhance
      graft healing in ACL reconstruction in humans is still being studied. CONSLUSIONS
      The use of PRP in ACL reconstruction does not accelerate graft remodelling and
      bone ingrowth into the tendon. The function scoring results showed a
      statistically significant improvement in knee function between 3 and 12 months of
      followup within each group studied but revealed no difference between the groups.
      The hypothesis postulated above was disproved. Key words: anterior cruciate
      ligament, platelet-rich plasma, anatomic single-bundle reconstruction. 

PMID- 26317185
TI  - Biomechanical comparison of dynamic hip screw, proximal femoral nail, cannulated
      screw, and monoaxial external fixation in the treatment of basicervical femoral
      neck fractures.
AB  - PURPOSE OF THE STUDY The objective of this study was to establish relative
      fixation strengths of proximal femoral nail (PFN), dynamic hip screw (DHS),
      monolateral external fixator (EF), and cannulated screw (CS) in basicervical hip
      fracture model. MATERIAL AND METHODS The study involved four groups of implanted
      composite proximal femoral synthetic bones of eight specimens per group; nailing
      with PFN, DHS, fixation with three cannulated screws, and EF. 70 osteotomy was
      performed to simulate a Pauwels Type 3 basicervical fracture. Minimum preload of
      100 N was applied before loading to failure. The constructs were subjected to
      cyclic loading with 16 to midline from 100 N to 1,000 N for 10,000 cycles at 3Hz.
      Axial loading was applied at 10 mm/min until failure. Failure load, failure mode,
      and displacement were documented. RESULTS Mean failure load was 2182.5 +/- 377.9
      N in PFN group, 2008.75 +/- 278.4 N in DHS group, 1941.25 +/- 171.6 N in EF
      group, and 1551.6 +/- 236.2 N in CS group. Average displacement was 15.6 +/- 4.5
      mm, 15.5 +/- 6.7 mm, 11.7 +/- 1.9 mm, and 15 +/- 1.7 mm, respectively. No
      significant difference was noted among groups for fixation strength except CS
      group. All CS constructs failed during cyclic loading. CONCLUSION Our findings
      suggest that PFN, DHS and EF achieved higher fixation strengths than CS in
      basicervical fracture. PFN has higher failure loads and possesses biomechanical
      benefits for fixation of unstable basicervical fractures compared with DHS and
      EF. Key words: basicervical fracture, internal fixation, biomechanics. 

PMID- 26317186
TI  - [Use of the anatomical cemented femoral stem SAS I: mid-term results].
AB  - PURPOSE OF THE STUDY In view of increasing interest in a relationship between the
      surface of an implant and its behaviour and longevity in total hip arthroplasty
      (THA), the aim of this study is to present the clinical and radiographic results,
      as well as complications, of hip replacement surgery using the cemented femoral
      stem SAS I. MATERIAL AND METHODS A total of 298 cemented femoral stems SAS I were
      implanted in 275 patients at our department between 1996 and 2005. The patient
      average age was 72.1 years, with the range from 64 to 92 years. The pre-operative
      diagnoses were as follows: primary osteoarthritis in 179 (30.1%); post-dysplastic
      osteoarthritis in 41 (13.7%); femoral neck fracture in 44 (14.8%); avascular
      necrosis of the femoral head in 23 (7.7%); rheumatoid arthritis in nine (3%) and
      other causes in two (0.7%) patients. Of the 275 patients who had the surgery, 186
      (204 THAs) underwent clinical and X-ray examination at an average follow-up of
      11.5 years (range, 8 to 17 years). The clinical results were used to calculate
      the Harris hip score and radiographic evaluation was based on antero-posterior
      views. RESULTS The group of 186 assessed patients (204 THAs) comprised 106 women
      and 80 men, who were on average 85.4 years old on evaluation (range, 72 to 92
      years). Of the remaining patients, 62 patients (64 THAs) died from causes
      unrelated to the surgery and 27 patients (30 THAs) were lost to follow-up. The
      functional outcome of surgery assessed by the Harris hip score was excellent in
      61 (32.8%), good in 94 (50.5%), satisfactory in 26 (14%) and poor in five (2.7%)
      patients. The 93.1% SAS I stem longevity was recorded in relation to aseptic
      loosening; reimplantation for this indication was performed in 14 THAs. No
      revision surgery for failure due to valgus/varus deviations of the stem was
      carried out. Of the 204 hips, 188 had femoral stems aligned in neutral, 12 (5.9%)
      in valgus and four (2%) in varus positions. DISCUSSION The anatomical femoral
      stem SAS I is an implant made to fit the proximal femur anatomy. Its highly
      polished surface allows for optimal fitting with the supporting bone and for even
      distribution of weight bearing. This results in a low rate of THA failure. In
      accordance with the relevant literature, the acetabular components is considered
      to be the weakest element in total hip replacement in terms of aseptic loosening
      and implant failure. At present, the SAS I stem has no Morse Eurocone taper and
      this is the chief obstacle hindering its more frequent use in endoprosthetics.
      CONCLUSIONS The results of our study are in agreement with those of other
      successfully implanted polished cemented femoral components. Key words:
      anatomical cemented femoral component, surface adjustment of the femoral stem,
      complications. 

PMID- 26317187
TI  - [The presence of the os peroneum and relative metatarsal length - X-ray study].
AB  - PURPOSE OF THE STUDY The os peroneum is a sesamoid bone found within the peroneus
      longus tendon and is present in the form of ossification on radiographs in 8-26%
      of the population. It is most likely the result of stress in the lateral side of
      the foot in connection with genetic factors. The factors affecting os peroneum
      development include anatomical changes, among others the length of the
      metatarsals especially because of the main tendon insertion on the first
      metatarsal bone. MATERIAL AND METHODS In the study, 768 standardised radiographs
      of feet of the Caucasian population, taken between 2006 and 2012 in the Vamed
      Mediterra hospital (Mostiste, Czech Republic), were investigated. The median age
      of the patients was 42 years, the range 18-75 years. The presence of an os
      peroneum was assessed and metatarsal length was measured by a modified method of
      Maestro. RESULTS The os peroneum was identified in 106 subjects (13.8%). Among
      the groups established according to the presence of os peroneum and its relation
      to the length of a metatarsal bone, the relationship with the first metatarsal
      (1+) was most frequent; it was seven-fold higher compared to the other variants.
      On the contrary, the variant 3+ was least frequent in the presence of the os
      peroneum. CONCLUSIONS The study presents a statistically significant relationship
      between the presence of the os peroneum and the length of the first metatarsal
      bone. Potentially, this is one of the causes of forefoot pain in relation to the
      os peroneum development and anatomical connections in this area. Key words: os
      peroneum, relative metatarsal length. 

PMID- 26317188
TI  - Sequential subtrochanteric femoral fracture after atypical diaphyseal fracture in
      a long-term bisphosphonate user: a case report.
AB  - Recent reports have found a relationship between long-term bisphosphonate therapy
      and the occurrence of low-energy subtrochanteric or diaphyseal atypical femoral
      fractures. These fractures usually occur at only one site in the same bone. We
      report a rare case of a patient with sequential atypical femoral fractures
      (first, a diaphyseal fracture, and second, an ipsilateral subtrochanteric
      fracture) after low-energy trauma. We present the clinical and operative findings
      and discuss how to prevent subsequent atypical femoral fractures. This case
      indicates that an atypical subtrochanteric femoral fracture can occur after an
      atypical diaphyseal fracture in a long-term bisphosphonate user. Doctors should
      be aware of the possibility of a second fracture and explain the risk to the
      patient. Key words: bisphosphonate, atypical femoral fracture, low-energy trauma,
      subtrochanteric and diaphyseal femoral fractures. 

PMID- 26317189
TI  - [Two siblings with bilateral congenital knee dislocations: case report].
AB  - Congenital dislocation of the knee and congenital permanent dislocation of the
      patella are rare disorders usually associated with complex syndromes. Two cases
      of siblings, girl and boy, who had the same clinical phenotype of this disorder
      are presented. The diagnosis of Desbuquois dysplasia was made and its autosomal
      recessive heredity was confirmed by genetic analysis. DNA samples were sent for a
      molecular genetic analysis of the skeletal dysplasia. The girl was surgically
      treated for a complete (grade 3) anterior dislocation of the tibia on the femur
      in the first year of life. Redressing casts had not previously been applied to
      avoid the risk of damaging the epiphysis. The left knee was operated on by the
      method, as described by Curtis and Fisher, at the age of six months. The
      Kirschner wire was removed after one month and a plaster cast was applied to
      maintain the flexion required. At seven post-operative weeks physiotherapy was
      started with temporary use of a knee brace. The right knee was managed by a
      similar procedure at four months after the first surgery. Normal walking was
      achieved at the age of 21 months. Knee motion was symmetrically restricted, with
      5 to 90 degrees of flexion. The boy was first seen at our out-patient department
      after his sister had achieved full walking ability. He was 10 years old at that
      time and presented with walking problems due to nearly 30 degrees of bilateral
      knee contractures. Permanent dislocation of both patellae was treated by the
      surgical technique described by Stanisavljevic. Revision surgery of the right
      knee due to patellar lateralization was required two years after the primary
      surgery; it was performed using the Campbell's technique. A corrective osteotomy
      of the left proximal tibia because of progressive genu valgum was carried out at
      four years following the first operation. At the last follow-up, the boy was 16
      years old and the knee range of motion bilaterally was 0 to 120 degrees with good
      alignment of both knees. As a result of surgical treatment the two patients
      gained ability to walk without problems. Key words: bilateral congenital knee
      dislocation, patella, Desbuquois dysplasia, siblings, skeletal dysplasia, case
      report. 

PMID- 26317190
TI  - Qualification and application of a liquid chromatography-quadrupole time-of
      flight mass spectrometric method for the determination of trastuzumab in rat
      plasma.
AB  - An liquid chromatography-quadrupole time-of-flight (QqTOF) mass spectrometric
      method was developed for the determination of humanized or human monoclonal
      antibodies in rat plasma at the early drug discovery stage. Trastuzumab was used
      as a model monoclonal antibody. The method consisted of immunoprecipitation
      followed by tryptic digestion for sample preparation and LC-TOF-MS/MS analysis of
      specific signature peptides in the positive ion mode using electrospray
      ionization for analysis. A stable isotope-labeled signature peptide was also used
      as internal standard. A quadratic regression (weighted 1/concentration(2) ), with
      an equation y = ax(2)  + bx + c, was used to fit calibration curves over the
      concentration range of 0.500-100 ug/mL for trastuzumab. Samples from a
      pharmacokinetic study in rat were analyzed by this qualified LC-TOF-MS/MS method
      and concentrations were compared with those generated by enzyme linked
      immunosorbent assays method. The LC-TOF-MS/MS method was accurate and precise,
      with quantitative results comparable with those of ELISA. The qualification run
      met the acceptance criteria of +/-25% accuracy and precision values for quality
      control samples. Within-run accuracy ranged from 1.53 to 9.20% with precision
      values <=10.29%. This LC-TOF-MS/MS method approach could be used as a
      complementary method for humanized or human monoclonal antibodies at the early
      drug discovery stage.

PMID- 26317191
TI  - Interpretation of angular symmetries in electron nanodiffraction patterns from
      thin amorphous specimens.
AB  - The interpretation of angular symmetries in electron nanodiffraction patterns
      from thin amorphous specimens is examined. It is found that in general there are
      odd symmetries in experimental electron nanodiffraction patterns. Using
      simulation, it is demonstrated that this effect can be attributed to dynamical
      scattering, rather than other divergences from the ideal experimental conditions
      such as probe-forming lens aberrations and camera noise. The departure of
      opposing diffracted intensities from Friedel's law in the phase grating formalism
      is calculated using a general structure factor for disordered materials. On the
      basis of this, a simple correction procedure is suggested to recover the
      kinematical angular symmetries, and thus readily interpretable information that
      reflects the symmetries of the original projected object. This correction is
      numerically tested using both the phase object and multislice calculations, and
      is demonstrated to fully recover all the kinematical diffracted symmetries from a
      simulated atomic model of a metallic glass. 

PMID- 26317192
TI  - Solution of the phase problem at non-atomic resolution by the phantom derivative
      method.
AB  - For a given unknown crystal structure (the target), n random structures,
      arbitrarily designed without any care for their chemical consistency and usually
      uncorrelated with the target, are sheltered in the same unit cell as the target
      structure and submitted to the same space-group symmetry. (These are called ancil
      structures.) The composite structures, whose electron densities are the sum of
      the target and of the ancil electron densities, are denoted derivatives. No
      observed diffraction amplitudes are available for them: in order to emphasize
      their unreal nature, the term phantom is added. The paper describes the
      theoretical basis by which the phantom derivative method may be used to phase the
      target structure. It may be guessed that 100-300 ancil structures may be
      sufficient for phasing a target structure, so that the phasing technique may be
      denoted as the multiple phantom derivative method. Ancil phases and amplitudes
      may be initially combined with observed target magnitudes to estimate amplitudes
      and phases of the corresponding phantom derivative. From them suitable algorithms
      allow one to obtain poor target phase estimates, which are often improved by
      combining the indications arising from each derivative. Probabilistic criteria
      are described to recognize the most reliable target phase estimates. The method
      is cyclic: the target phase estimates just obtained are used to improve
      amplitudes and phases of each derivative, which, in their turn, are employed to
      provide better target phase estimates. The method is a fully ab initio method,
      because it needs only the experimental data of the target structure. The term
      derivative is maintained with reference to SIR-MIR (single isomorphous
      replacement-multiple isomorphous replacement) techniques, even if its meaning is
      different: therefore the reader should think of the phantom derivative method
      more as a new method than as a variant of SIR-MIR techniques. The differences are
      much greater than the analogies. The paper also describes how phantom derivatives
      may be used for improving structure models obtained via other ab initio or non-ab
      initio techniques. The method is expected to be insensitive to the structural
      complexity of the target and to the target experimental data resolution, provided
      it is better than 4-6 A. 

PMID- 26317193
TI  - Theoretical analysis of reflection high-energy electron diffraction (RHEED) and
      reflection high-energy positron diffraction (RHEPD) intensity oscillations
      expected for the perfect layer-by-layer growth.
AB  - Predictions from two theoretical models, allowing one to determine the phase of
      intensity oscillations, are compared for reflected beams of electrons and
      positrons. Namely, results of the precise dynamical calculations are compared
      with results obtained using a simplified approach. Within the simplified model,
      changes in the specularly reflected beam intensity, expected to occur during the
      deposition of new atoms, are described with the help of interfering waves and the
      effect of refraction, and respective approximate analytical formulas are employed
      to determine the phase of the oscillations. It is found that the simplified model
      is very useful for understanding the physics ruling the appearance of intensity
      oscillations. However, it seems that the model with the realistic potential is
      more suitable for carrying out interpretations of experimental data. 

PMID- 26317194
TI  - A study of X-ray multiple diffraction by means of section topography.
AB  - The results of theoretical and experimental study are presented for the question
      of how the X-ray multiple diffraction in a silicon single crystal influences the
      interference fringes of section topography for the 400 reflection in the Laue
      case. Two different cases of multiple diffraction are discovered for zero and
      very small values of the azimuthal angle for the sample in the form of a plate
      with the surface normal to the 001 direction. The cases are seen on the same
      topogram without rotation of the crystal. Accurate computer simulations of the
      section topogram for the case of X-ray multiple diffraction are performed for the
      first time. It is shown that the structure of interference fringes on the section
      topogram in the region of multiple diffraction becomes more complicated. It has a
      very sharp dependence on the azimuthal angle. The experiment is carried out using
      a laboratory source under conditions of low resolution over the azimuthal angle.
      Nevertheless, the characteristic inclination of the interference fringes on the
      tails of the multiple diffraction region is easily seen. This phenomenon
      corresponds completely to the computer simulations. 

PMID- 26317195
TI  - Image definition evaluation functions for X-ray crystallography: a new
      perspective on the phase problem.
AB  - The core theme of X-ray crystallography is reconstructing the electron-density
      distribution of crystals under the constraints of observed diffraction data.
      Nevertheless, reconstruction of the electron-density distribution by
      straightforward Fourier synthesis is usually hindered due to the well known phase
      problem and the finite resolution of diffraction data. In analogy with optical
      imaging systems, the reconstructed electron-density map may be regarded as the
      image of the real electron-density distribution in crystals. Inspired by image
      definition evaluation functions applied in the auto-focusing process, two
      evaluation functions are proposed for the reconstructed electron-density images.
      One of them is based on the atomicity of the electron-density distribution and
      properties of Fourier synthesis. Tests were performed on synthetic data of known
      structures, and it was found that this evaluation function can distinguish the
      correctly reconstructed electron-density image from wrong ones when diffraction
      data of atomic resolution are available. An algorithm was established based on
      this evaluation function and applied in reconstructing the electron-density image
      from the synthetic data of known structures. The other evaluation function, which
      is based on the positivity of electron density and constrained power spectrum
      entropy maximization, was designed for cases where only diffraction data of
      rather limited resolution are available. Tests on the synthetic data indicate
      that this evaluation function may identify the correct phase set even for a data
      set with resolution as low as 3.5 A. Though no algorithm for structure solution
      has been figured out based on the latter function, the results presented here
      provide a new perspective on the phase problem. 

PMID- 26317196
TI  - Neutron interferometric measurement and calculations of a phase shift induced by
      Laue transmission.
AB  - This study investigates the phase shift induced by Laue transmission in a perfect
      Si crystal blade in unprecedented detail. This 'Laue phase' was measured at two
      wavelengths in the vicinity of the Bragg condition within a neutron
      interferometer. In particular, the sensitivity of the Laue phase to the alignment
      of the monochromator and interferometer (rocking angle) and beam divergence has
      been verified. However, the influence of fundamental quantities, such as the
      neutron-electron scattering length, on the Laue phase is rather small. The
      fascinating steep phase slope of 5.5 degrees  [(220) Bragg peak] and 11.5 degrees
      [(440) Bragg peak] per 0.001 arcsec deviation from the Bragg angle has been
      achieved. The results are analysed using an upgraded simulation tool. 

PMID- 26317197
TI  - Three new crystal structures in the Na-Pb system: solving structures without
      additional experimental input.
AB  - The structures of three Na-Pb compounds, gamma, delta and delta', have remained
      incompletely solved for nearly 60 years. The space group, lattice parameters and
      positions of the Pb atoms of these three structures have been determined, but the
      positions of the Na atoms are still unknown. In this work, the First-Principles
      Assisted Structure Solution (FPASS) method [Meredig & Wolverton (2013). Nat.
      Mater. 12, 123-127] has been used to complete the description of these three
      structures using only experimental information available from the literature as
      input. The paper also discusses the relative advantages of constrained crystal
      structure prediction tools, like FPASS, in comparison to conventional crystal
      structure prediction methods in reference to their abilities to complete the
      solution of other unsolved structures. 

PMID- 26317198
TI  - Hexagonal projected symmetries.
AB  - In the study of pattern formation in symmetric physical systems, a three
      dimensional structure in thin domains is often modelled as a two-dimensional one.
      This paper is concerned with functions in {?bb R}^{3} that are invariant under
      the action of a crystallographic group and the symmetries of their projections
      into a function defined on a plane. A list is obtained of the crystallographic
      groups for which the projected functions have a hexagonal lattice of periods. The
      proof is constructive and the result may be used in the study of observed
      patterns in thin domains, whose symmetries are not expected in two-dimensional
      models, like the black-eye pattern. 

PMID- 26317199
TI  - Novel Gallate Triphenylphosphonium Derivatives with Potent Antichagasic Activity.
AB  - disease is one of the most neglected tropical diseases in the world, affecting
      nearly 15 million people, primarily in Latin America. Only two drugs are used for
      the treatment of this disease, nifurtimox and benznidazole. These drugs have
      limited efficacy and frequently induce adverse effects, limiting their
      usefulness. Consequently, new drugs must be found. In this study, we demonstrated
      the in vitro trypanocidal effects of a series of four gallic acid derivatives
      characterized by a gallate group linked to a triphenylphosphonium (TPP(+)) moiety
      (a delocalized cation) via a hydrocarbon chain of 8, 10, 11, or 12 atoms (TPP(+)
      C8, TPP(+)-C10, TPP(+)-C11, and TPP(+)-C12, respectively). We analyzed parasite
      viability in isolated parasites (by MTT reduction and flow cytometry) and
      infected mammalian cells using T. cruzi Y strain trypomastigotes. Among the four
      derivatives, TPP(+)-C10 and TPP(+)-C12 were the most potent in both models, with
      EC50 values (in isolated parasites) of 1.0 +/- 0.6 and 1.0 +/- 0.7 MUM,
      respectively, and were significantly more potent than nifurtimox (EC50 = 4.1 +/-
      0.6 MUM). At 1 MUM, TPP(+)-C10 and TPP(+)-C12 induced markers of cell death, such
      as phosphatidylserine exposure and propidium iodide permeabilization. In
      addition, at 1 MUM, TPP(+)-C10 and TPP(+)-C12 significantly decreased the number
      of intracellular amastigotes (TPP(+)-C10: 24.3%, TPP(+)-C12: 19.0% of control
      measurements, as measured by DAPI staining) and the parasite's DNA load (C10:
      10%, C12: 13% of control measurements, as measured by qPCR). Based on the
      previous mode of action described for these compounds in cancer cells, we
      explored their mitochondrial effects in isolated trypomastigotes. TPP(+)-C10 and
      TPP(+)-C12 were the most potent compounds, significantly altering mitochondrial
      membrane potential at 1 MUM (measured by JC-1 fluorescence) and inducing
      mitochondrial transition pore opening at 5 MUM. Taken together, these results
      indicate that the TPP(+)-C10 and TPP(+)-C12 derivatives of gallic acid are
      promising trypanocidal agents with mitochondrial activity.

PMID- 26317200
TI  - Co-Flocculation of Yeast Species, a New Mechanism to Govern Population Dynamics
      in Microbial Ecosystems.
AB  - Flocculation has primarily been studied as an important technological property of
      Saccharomyces cerevisiae yeast strains in fermentation processes such as brewing
      and winemaking. These studies have led to the identification of a group of
      closely related genes, referred to as the FLO gene family, which controls the
      flocculation phenotype. All naturally occurring S. cerevisiae strains assessed
      thus far possess at least four independent copies of structurally similar FLO
      genes, namely FLO1, FLO5, FLO9 and FLO10. The genes appear to differ primarily by
      the degree of flocculation induced by their expression. However, the reason for
      the existence of a large family of very similar genes, all involved in the same
      phenotype, has remained unclear. In natural ecosystems, and in wine production,
      S. cerevisiae growth together and competes with a large number of other
      Saccharomyces and many more non-Saccharomyces yeast species. Our data show that
      many strains of such wine-related non-Saccharomyces species, some of which have
      recently attracted significant biotechnological interest as they contribute
      positively to fermentation and wine character, were able to flocculate
      efficiently. The data also show that both flocculent and non-flocculent S.
      cerevisiae strains formed mixed species flocs (a process hereafter referred to as
      co-flocculation) with some of these non-Saccharomyces yeasts. This ability of
      yeast strains to impact flocculation behaviour of other species in mixed inocula
      has not been described previously. Further investigation into the genetic
      regulation of co-flocculation revealed that different FLO genes impact
      differently on such adhesion phenotypes, favouring adhesion with some species
      while excluding other species from such mixed flocs. The data therefore strongly
      suggest that FLO genes govern the selective association of S. cerevisiae with
      specific species of non-Saccharomyces yeasts, and may therefore be drivers of
      ecosystem organisational patterns. Our data provide, for the first time, insights
      into the role of the FLO gene family beyond intraspecies cellular association,
      and suggest a wider evolutionary role for the FLO genes. Such a role would
      explain the evolutionary persistence of a large multigene family of genes with
      apparently similar function. 

PMID- 26317201
TI  - Differences in Retinal Structure and Function between Aging Male and Female
      Sprague-Dawley Rats are Strongly Influenced by the Estrus Cycle.
AB  - PURPOSE: Biological sex and age are considered as two important factors that may
      influence the function and structure of the retina, an effect that might be
      governed by sexual hormones such as estrogen. The purpose of this study was to
      delineate the influence that biological sex and age exert on the retinal function
      and structure of rodents and also clarify the effect that the estrus cycle might
      exert on the retinal function of female rats. METHOD: The retinal function of 50
      normal male and female albino Sprague-Dawley (SD) rats was investigated with the
      electroretinogram (ERG) at postnatal day (P) 30, 60, 100, 200, and 300 (n = 5-6
      male and female rats/age). Following the ERG recording sessions, retinal
      histology was performed in both sexes. In parallel, the retinal function of
      premenopausal and menopausal female rats aged P540 were also compared. RESULTS:
      Sex and age-related changes in retinal structure and function were observed in
      our animal model. However, irrespective of age, no significant difference was
      observed in ERG and retinal histology obtained from male and female rats.
      Notwithstanding the above we did however notice that between P60 and P200 there
      was a gradual increase in ERG amplitudes of female rats compared to males.
      Furthermore, the ERG of premenopausal female rats aged 18 months old (P540) was
      larger compared to age-matched menopausal female rats as well as that of male
      rats. CONCLUSION: Our results showed that biological sex and age can influence
      the retinal function and structure of albino SD rats. Furthermore, we showed that
      cycled female rats have better retinal function compared to the menopausal female
      rats suggesting a beneficial effect of the estrus cycle on the retinal function.

PMID- 26317202
TI  - Clustering and Differential Alignment Algorithm: Identification of Early Stage
      Regulators in the Arabidopsis thaliana Iron Deficiency Response.
AB  - Time course transcriptome datasets are commonly used to predict key gene
      regulators associated with stress responses and to explore gene functionality.
      Techniques developed to extract causal relationships between genes from high
      throughput time course expression data are limited by low signal levels coupled
      with noise and sparseness in time points. We deal with these limitations by
      proposing the Cluster and Differential Alignment Algorithm (CDAA). This algorithm
      was designed to process transcriptome data by first grouping genes based on
      stages of activity and then using similarities in gene expression to predict
      influential connections between individual genes. Regulatory relationships are
      assigned based on pairwise alignment scores generated using the expression
      patterns of two genes and some inferred delay between the regulator and the
      observed activity of the target. We applied the CDAA to an iron deficiency time
      course microarray dataset to identify regulators that influence 7 target
      transcription factors known to participate in the Arabidopsis thaliana iron
      deficiency response. The algorithm predicted that 7 regulators previously
      unlinked to iron homeostasis influence the expression of these known
      transcription factors. We validated over half of predicted influential
      relationships using qRT-PCR expression analysis in mutant backgrounds. One
      predicted regulator-target relationship was shown to be a direct binding
      interaction according to yeast one-hybrid (Y1H) analysis. These results serve as
      a proof of concept emphasizing the utility of the CDAA for identifying unknown or
      missing nodes in regulatory cascades, providing the fundamental knowledge needed
      for constructing predictive gene regulatory networks. We propose that this tool
      can be used successfully for similar time course datasets to extract additional
      information and infer reliable regulatory connections for individual genes. 

PMID- 26317203
TI  - Progression of Osteosarcoma from a Non-Metastatic to a Metastatic Phenotype Is
      Causally Associated with Activation of an Autocrine and Paracrine uPA Axis.
AB  - Pulmonary metastasis is the major untreatable complication of osteosarcoma (OS)
      resulting in 10-20% long-term survival. The factors and pathways regulating these
      processes remain unclear, yet their identification is crucial in order to find
      new therapeutic targets. In this study we used a multi-omics approach to identify
      molecules in metastatic and non-metastatic OS cells that may contribute to OS
      metastasis, followed by validation in vitro and in vivo. We found elevated levels
      of the urokinase plasminogen activator (uPA) and of the uPA receptor (uPAR)
      exclusively in metastatic OS cells. uPA was secreted in soluble form and as part
      of the protein cargo of OS-secreted extracellular vesicles, including exosomes.
      In addition, in the tumour microenvironment, uPA was expressed and secreted by
      bone marrow cells (BMC), and OS- and BMC-derived uPA significantly and
      specifically stimulated migration of metastatic OS cells via uPA-dependent
      signaling pathways. Silencing of uPAR in metastatic OS cells abrogated the
      migratory response to uPA in vitro and decreased metastasis in vivo. Finally, a
      novel small-molecule inhibitor of uPA significantly (P = 0.0004) inhibited
      metastasis in an orthotopic mouse model of OS. Thus, we show for the first time
      that malignant conversion of OS cells to a metastatic phenotype is defined by
      activation of the uPA/uPAR axis in both an autocrine and paracrine fashion.
      Furthermore, metastasis is driven by changes in OS cells as well as in the
      microenvironment. Finally, our data show that pharmacological inhibition of the
      uPA/uPAR axis with a novel small-molecule inhibitor can prevent the emergence of
      metastatic foci. 

PMID- 26317204
TI  - Implementation of Contraction to Electrophysiological Ventricular Myocyte Models,
      and Their Quantitative Characterization via Post-Extrasystolic Potentiation.
AB  - Heart failure (HF) affects over 5 million Americans and is characterized by
      impairment of cellular cardiac contractile function resulting in reduced ejection
      fraction in patients. Electrical stimulation such as cardiac resynchronization
      therapy (CRT) and cardiac contractility modulation (CCM) have shown some success
      in treating patients with HF. Computer simulations have the potential to help
      improve such therapy (e.g. suggest optimal lead placement) as well as provide
      insight into the underlying mechanisms which could be beneficial. However, these
      myocyte models require a quantitatively accurate excitation-contraction coupling
      such that the electrical and contraction predictions are correct. While currently
      there are close to a hundred models describing the detailed electrophysiology of
      cardiac cells, the majority of cell models do not include the equations to
      reproduce contractile force or they have been added ad hoc. Here we present a
      systematic methodology to couple first generation contraction models into
      electrophysiological models via intracellular calcium and then compare the
      resulting model predictions to experimental data. This is done by using a post
      extrasystolic pacing protocol, which captures essential dynamics of contractile
      forces. We found that modeling the dynamic intracellular calcium buffers is
      necessary in order to reproduce the experimental data. Furthermore, we
      demonstrate that in models the mechanism of the post-extrasystolic potentiation
      is highly dependent on the calcium released from the Sarcoplasmic Reticulum.
      Overall this study provides new insights into both specific and general
      determinants of cellular contractile force and provides a framework for
      incorporating contraction into electrophysiological models, both of which will be
      necessary to develop reliable simulations to optimize electrical therapies for
      HF. 

PMID- 26317206
TI  - Persistent Spatial Clusters of Prescribed Antimicrobials among Danish Pig Farms-
      A Register-Based Study.
AB  - The emergence of pathogens resistant to antimicrobials has prompted political
      initiatives targeting a reduction in the use of veterinary antimicrobials in
      Denmark, especially for pigs. This study elucidates the tendency of pig farms
      with a significantly higher antimicrobial use to remain in clusters in certain
      geographical regions of Denmark. Animal Daily Doses/100 pigs/day were calculated
      for all three age groups of pigs (weaners, finishers and sows) for each quarter
      during 2012-13 in 6,143 commercial indoor pig producing farms. The data were
      split into four time periods of six months. Repeated spatial cluster analyses
      were performed to identify persistent clusters, i.e. areas included in a
      significant cluster throughout all four time periods. Antimicrobials prescribed
      for weaners did not result in any persistent clusters. In contrast, antimicrobial
      use in finishers clustered persistently in two areas (157 farms), while those
      issued for sows clustered in one area (51 farms). A multivariate analysis
      including data on antimicrobial use for weaners, finishers and sows as three
      separate outcomes resulted in three persistent clusters (551 farms). Compared to
      farms outside the clusters during this period, weaners, finishers and sows on
      farms within these clusters had 19%, 104% and 4% higher use of antimicrobials,
      respectively. Production type, farm type and farm size seemed to have some
      bearing on the clustering effect. Adding these factors as categorical covariates
      one at a time in the multivariate analysis reduced the persistent clusters by
      24.3%, 30.5% and 34.1%, respectively. 

PMID- 26317205
TI  - Protein Aggregation Formed by Recombinant cp19k Homologue of Balanus albicostatus
      Combined with an 18 kDa N-Terminus Encoded by pET-32a(+) Plasmid Having Adhesion
      Strength Comparable to Several Commercial Glues.
AB  - The barnacle is well known for its tenacious and permanent attachment to a wide
      variety of underwater substrates, which is accomplished by synthesizing,
      secreting and curing a mixture of adhesive proteins termed "barnacle cement". In
      order to evaluate interfacial adhesion abilities of barnacle cement proteins, the
      cp19k homologous gene in Balanus albicostatus (Balcp19k) was cloned and expressed
      in Escherichia coli. Here, we report an intriguing discovery of a gel-like super
      adhesive aggregation produced by Trx-Balcp19k, a recombinant Balcp19k fusion
      protein. The Trx-Balcp19k consists of an 18 kDa fragment at the N-terminus, which
      is encoded by pET-32a(+) plasmid and mainly comprised of a thioredoxin (Trx) tag,
      and Balcp19k at the C-terminus. The sticky aggregation was designated as "Trx
      Balcp19k gel", and the bulk adhesion strength, biochemical composition, as well
      as formation conditions were all carefully investigated. The Trx-Balcp19k gel
      exhibited strong adhesion strength of 2.10 +/- 0.67 MPa, which was approximately
      fifty folds higher than that of the disaggregated Trx-Balcp19k (40 +/- 8 kPa) and
      rivaled those of commercial polyvinyl acetate (PVA) craft glue (Mont Marte,
      Australia) and UHU glue (UHU GmbH & Co. KG, Germany). Lipids were absent from the
      Trx-Balcp19k gel and only a trace amount of carbohydrates was detected. We
      postulate that the electrostatic interactions play a key role in the formation of
      Trx-Balcp19k gel, by mediating self-aggregation of Trx-Balcp19k based on its
      asymmetric distribution pattern of charged amino acids. Taken together, we
      believe that our discovery not only presents a promising biological adhesive with
      potential applications in both biomedical and technical fields, but also provides
      valuable paradigms for molecular design of bio-inspired peptide- or protein-based
      materials. 

PMID- 26317207
TI  - Leptomonas seymouri: Adaptations to the Dixenous Life Cycle Analyzed by Genome
      Sequencing, Transcriptome Profiling and Co-infection with Leishmania donovani.
AB  - The co-infection cases involving dixenous Leishmania spp. (mostly of the L.
      donovani complex) and presumably monoxenous trypanosomatids in immunocompromised
      mammalian hosts including humans are well documented. The main opportunistic
      parasite has been identified as Leptomonas seymouri of the sub-family
      Leishmaniinae. The molecular mechanisms allowing a parasite of insects to
      withstand elevated temperature and substantially different conditions of
      vertebrate tissues are not understood. Here we demonstrate that L. seymouri is
      well adapted for the environment of the warm-blooded host. We sequenced the
      genome and compared the whole transcriptome profiles of this species cultivated
      at low and high temperatures (mimicking the vector and the vertebrate host,
      respectively) and identified genes and pathways differentially expressed under
      these experimental conditions. Moreover, Leptomonas seymouri was found to persist
      for several days in two species of Phlebotomus spp. implicated in Leishmania
      donovani transmission. Despite of all these adaptations, L. seymouri remains a
      predominantly monoxenous species not capable of infecting vertebrate cells under
      normal conditions. 

PMID- 26317208
TI  - Attenuation of Cerebral Ischemic Injury in Smad1 Deficient Mice.
AB  - Stroke results in brain tissue damage from ischemia and oxidative stress.
      Molecular regulators of the protective versus deleterious cellular responses
      after cerebral ischemia remain to be identified. Here, we show that deletion of
      Smad1, a conserved transcription factor that mediates canonical bone
      morphogenetic protein (BMP) signaling, results in neuroprotection in an ischemia
      reperfusion (I/R) stroke model. Uninjured mice with conditional deletion of Smad1
      in the CNS (Smad1 cKO) displayed upregulation of the reactive astrocyte marker
      GFAP and hypertrophic morphological changes in astrocytes compared to littermate
      controls. Additionally, cultured Smad1(-/-) astrocytes exhibited an enhanced
      antioxidant capacity. When subjected to I/R injury by transient middle cerebral
      artery occlusion (tMCAO), Smad1 cKO mice showed enhanced neuronal survival and
      improved neurological recovery at 7 days post-stroke. This neuroprotective
      phenotype is associated with attenuated reactive astrocytosis and
      neuroinflammation, along with reductions in oxidative stress, p53 induction, and
      apoptosis. Our data suggest that Smad1-mediated signaling pathway is involved in
      stroke pathophysiology and may present a new potential target for stroke therapy.

PMID- 26317209
TI  - DNA-Methylation Patterns in Trisomy 21 Using Cells from Monozygotic Twins.
AB  - DNA methylation is essential in mammalian development. We have hypothesized that
      methylation differences induced by trisomy 21 (T21) contribute to the phenotypic
      characteristics and heterogeneity in Down syndrome (DS). In order to determine
      the methylation differences in T21 without interference of the interindividual
      genomic variation, we have used fetal skin fibroblasts from monozygotic (MZ)
      twins discordant for T21. We also used skin fibroblasts from MZ twins concordant
      for T21, normal MZ twins without T21, and unrelated normal and T21 individuals.
      Reduced Representation Bisulfite Sequencing (RRBS) revealed 35 differentially
      methylated promoter regions (DMRs) (Absolute methylation differences = 25%, FDR <
      0.001) in MZ twins discordant for T21 that have also been observed in comparison
      between unrelated normal and T21 individuals. The identified DMRs are enriched
      for genes involved in embryonic organ morphogenesis (FDR = 1.60 e -03) and
      include genes of the HOXB and HOXD clusters. These DMRs are maintained in iPS
      cells generated from this twin pair and are correlated with the gene expression
      changes. We have also observed an increase in DNA methylation level in the T21
      methylome compared to the normal euploid methylome. This observation is
      concordant with the up regulation of DNA methyltransferase enzymes (DNMT3B and
      DNMT3L) and down regulation of DNA demethylation enzymes (TET2 and TET3) observed
      in the iPSC of the T21 versus normal twin. Altogether, the results of this study
      highlight the epigenetic effects of the extra chromosome 21 in T21 on loci
      outside of this chromosome that are relevant to DS associated phenotypes. 

PMID- 26317210
TI  - A Multiple Antigenic Peptide Mimicking Peptidoglycan Induced T Cell Responses to
      Protect Mice from Systemic Infection with Staphylococcus aureus.
AB  - Due to the enormous capacity of Staphylococcus aureus to acquire antibiotic
      resistance, it becomes imperative to develop vaccines for decreasing the risk of
      its life-threatening infections. Peptidoglycan (PGN) is a conserved and major
      component of S. aureus cell wall. However, it has not been used as a vaccine
      candidate since it is a thymus-independent antigen. In this study, we synthesized
      a multiple antigenic peptide, named MAP27, which comprised four copies of a
      peptide that mimics the epitope of PGN. After immunization with MAP27 five times
      and boosting with heat-inactivated bacterium one time, anti-MAP27 serum bound
      directly to S. aureus or PGN. Immunization with MAP27 decreased the bacterial
      burden in organs of BALB/c mice and significantly prolonged their survival time
      after S. aureus lethal-challenge. The percentage of IFN-gamma(+)CD3(+) T cells
      and IL-17(+)CD4(+) T cells in spleen, as well as the levels of IFN-gamma, IL
      17A/F and CCL3 in spleen and lung, significantly increased in the MAP27-immunized
      mice after infection. Moreover, in vitro incubation of heat-inactivated S. aureus
      with splenocytes isolated from MAP27-immunized mice stimulated the production of
      IFN-gamma and IL-17A/F. Our findings demonstrated that MAP27, as a thymus
      dependent antigen, is efficient at eliciting T cell-mediated responses to protect
      mice from S. aureus infection. This study sheds light on a possible strategy to
      design vaccines against S. aureus.

PMID- 26317211
TI  - C/EBPbeta Promotes Immunity to Oral Candidiasis through Regulation of beta
      Defensins.
AB  - Humans or mice subjected to immunosuppression, such as corticosteroids or anti
      cytokine biologic therapies, are susceptible to mucosal infections by the
      commensal fungus Candida albicans. Recently it has become evident that the
      Th17/IL-17 axis is essential for immunity to candidiasis, but the downstream
      events that control immunity to this fungus are poorly understood. The
      CCAAT/Enhancer Binding Protein-beta (C/EBPbeta) transcription factor is important
      for signaling by multiple inflammatory stimuli, including IL-17. C/EBPbeta is
      regulated in a variety of ways by IL-17, and controls several downstream IL-17
      target genes. However, the role of C/EBPbeta in vivo is poorly understood, in
      part because C/EBPbeta-deficient mice are challenging to breed and work with. In
      this study, we sought to understand the role of C/EBPbeta in the context of an IL
      17-dependent immune response, using C. albicans infection as a model system.
      Confirming prior findings, we found that C/EBPbeta is required for immunity to
      systemic candidiasis. In contrast, C/EBPbeta(-/-) mice were resistant to
      oropharyngeal candidiasis (OPC), in a manner indistinguishable from
      immunocompetent WT mice. However, C/EBPbeta(-/-) mice experienced more severe OPC
      than WT mice in the context of cortisone-induced immunosuppression. Expression of
      the antimicrobial peptide beta-defensin (BD)-3 correlated strongly with
      susceptibility in C/EBPbeta(-/-) mice, but no other IL-17-dependent genes were
      associated with susceptibility. Therefore, C/EBPbeta contributes to immunity to
      mucosal candidiasis during cortisone immunosuppression in a manner linked to beta
      defensin 3 expression, but is apparently dispensable for the IL-17-dependent
      response.

PMID- 26317212
TI  - Enrichment and Broad Representation of Plant Biomass-Degrading Enzymes in the
      Specialized Hyphal Swellings of Leucoagaricus gongylophorus, the Fungal Symbiont
      of Leaf-Cutter Ants.
AB  - Leaf-cutter ants are prolific and conspicuous constituents of Neotropical
      ecosystems that derive energy from specialized fungus gardens they cultivate
      using prodigious amounts of foliar biomass. The basidiomycetous cultivar of the
      ants, Leucoagaricus gongylophorus, produces specialized hyphal swellings called
      gongylidia that serve as the primary food source of ant colonies. Gongylidia also
      contain plant biomass-degrading enzymes that become concentrated in ant digestive
      tracts and are deposited within fecal droplets onto fresh foliar material as ants
      incorporate it into the fungus garden. Although the enzymes concentrated by L.
      gongylophorus within gongylidia are thought to be critical to the initial
      degradation of plant biomass, only a few enzymes present in these hyphal
      swellings have been identified. Here we use proteomic methods to identify
      proteins present in the gongylidia of three Atta cephalotes colonies. Our results
      demonstrate that a diverse but consistent set of enzymes is present in
      gongylidia, including numerous plant biomass-degrading enzymes likely involved in
      the degradation of polysaccharides, plant toxins, and proteins. Overall,
      gongylidia contained over three quarters of all biomass-degrading enzymes
      identified in the L. gongylophorus genome, demonstrating that the majority of the
      enzymes produced by this fungus for biomass breakdown are ingested by the ants.
      We also identify a set of 40 of these enzymes enriched in gongylidia compared to
      whole fungus garden samples, suggesting that certain enzymes may be particularly
      important in the initial degradation of foliar material. Our work sheds light on
      the complex interplay between leaf-cutter ants and their fungal symbiont that
      allows for the host insects to occupy an herbivorous niche by indirectly deriving
      energy from plant biomass. 

PMID- 26317214
TI  - An Improved F(st) Estimator.
AB  - The fixation index F(st) plays a central role in ecological and evolutionary
      genetic studies. The estimators of Wright ([Formula: see text]), Weir and
      Cockerham ([Formula: see text]), and Hudson et al. ([Formula: see text]) are
      widely used to measure genetic differences among different populations, but all
      have limitations. We propose a minimum variance estimator [Formula: see text]
      using [Formula: see text] and [Formula: see text]. We tested [Formula: see text]
      in simulations and applied it to 120 unrelated East African individuals from
      Ethiopia and 11 subpopulations in HapMap 3 with 464,642 SNPs. Our simulation
      study showed that [Formula: see text] has smaller bias than [Formula: see text]
      for small sample sizes and smaller bias than [Formula: see text] for large sample
      sizes. Also, [Formula: see text] has smaller variance than [Formula: see text]
      for small Fst values and smaller variance than [Formula: see text] for large
      F(st) values. We demonstrated that approximately 30 subpopulations and 30
      individuals per subpopulation are required in order to accurately estimate F(st).

PMID- 26317213
TI  - Characterization of Peptidyl-Prolyl Cis-Trans Isomerase- and Calmodulin-Binding
      Activity of a Cytosolic Arabidopsis thaliana Cyclophilin AtCyp19-3.
AB  - Cyclophilins, which bind to immunosuppressant cyclosporin A (CsA), are ubiquitous
      proteins and constitute a multigene family in higher organisms. Several members
      of this family are reported to catalyze cis-trans isomerisation of the peptidyl
      prolyl bond, which is a rate limiting step in protein folding. The physiological
      role of these proteins in plants, with few exceptions, is still a matter of
      speculation. Although Arabidopsis genome is predicted to contain 35 cyclophilin
      genes, biochemical characterization, imperative for understanding their cellular
      function(s), has been carried only for few of the members. The present study
      reports the biochemical characterization of an Arabidopsis cyclophilin, AtCyp19
      3, which demonstrated that this protein is enzymatically active and possesses
      peptidyl-prolyl cis-trans isomerase (PPIase) activity that is specifically
      inhibited by CsA with an inhibition constant (Ki) of 18.75 nM. The PPIase
      activity of AtCyp19-3 was also sensitive to Cu(2+), which covalently reacts with
      the sulfhydryl groups, implying redox regulation. Further, using calmodulin (CaM)
      gel overlay assays it was demonstrated that in vitro interaction of AtCyp19-3
      with CaM is Ca(2+)-dependent, and CaM-binding domain is localized to 35-70 amino
      acid residues in the N-terminus. Bimolecular fluorescence complementation assays
      showed that AtCyp19-3 interacts with CaM in vivo also, thus, validating the in
      vitro observations. However, the PPIase activity of the Arabidopsis cyclophilin
      was not affected by CaM. The implications of these findings are discussed in the
      context of Ca(2+) signaling and cyclophilin activity in Arabidopsis.

PMID- 26317215
TI  - Discovery of Drug Synergies in Gastric Cancer Cells Predicted by Logical
      Modeling.
AB  - Discovery of efficient anti-cancer drug combinations is a major challenge, since
      experimental testing of all possible combinations is clearly impossible. Recent
      efforts to computationally predict drug combination responses retain this
      experimental search space, as model definitions typically rely on extensive drug
      perturbation data. We developed a dynamical model representing a cell fate
      decision network in the AGS gastric cancer cell line, relying on background
      knowledge extracted from literature and databases. We defined a set of logical
      equations recapitulating AGS data observed in cells in their baseline
      proliferative state. Using the modeling software GINsim, model reduction and
      simulation compression techniques were applied to cope with the vast state space
      of large logical models and enable simulations of pairwise applications of
      specific signaling inhibitory chemical substances. Our simulations predicted
      synergistic growth inhibitory action of five combinations from a total of 21
      possible pairs. Four of the predicted synergies were confirmed in AGS cell growth
      real-time assays, including known effects of combined MEK-AKT or MEK-PI3K
      inhibitions, along with novel synergistic effects of combined TAK1-AKT or TAK1
      PI3K inhibitions. Our strategy reduces the dependence on a priori drug
      perturbation experimentation for well-characterized signaling networks, by
      demonstrating that a model predictive of combinatorial drug effects can be
      inferred from background knowledge on unperturbed and proliferating cancer cells.
      Our modeling approach can thus contribute to preclinical discovery of efficient
      anticancer drug combinations, and thereby to development of strategies to tailor
      treatment to individual cancer patients. 

PMID- 26317216
TI  - Exome Sequencing of Cell-Free DNA from Metastatic Cancer Patients Identifies
      Clinically Actionable Mutations Distinct from Primary Disease.
AB  - The identification of the molecular drivers of cancer by sequencing is the
      backbone of precision medicine and the basis of personalized therapy; however,
      biopsies of primary tumors provide only a snapshot of the evolution of the
      disease and may miss potential therapeutic targets, especially in the metastatic
      setting. A liquid biopsy, in the form of cell-free DNA (cfDNA) sequencing, has
      the potential to capture the inter- and intra-tumoral heterogeneity present in
      metastatic disease, and, through serial blood draws, track the evolution of the
      tumor genome. In order to determine the clinical utility of cfDNA sequencing we
      performed whole-exome sequencing on cfDNA and tumor DNA from two patients with
      metastatic disease; only minor modifications to our sequencing and analysis
      pipelines were required for sequencing and mutation calling of cfDNA. The first
      patient had metastatic sarcoma and 47 of 48 mutations present in the primary
      tumor were also found in the cell-free DNA. The second patient had metastatic
      breast cancer and sequencing identified an ESR1 mutation in the cfDNA and
      metastatic site, but not in the primary tumor. This likely explains tumor
      progression on Anastrozole. Significant heterogeneity between the primary and
      metastatic tumors, with cfDNA reflecting the metastases, suggested separation
      from the primary lesion early in tumor evolution. This is best illustrated by an
      activating PIK3CA mutation (H1047R) which was clonal in the primary tumor, but
      completely absent from either the metastasis or cfDNA. Here we show that cfDNA
      sequencing supplies clinically actionable information with minimal risks compared
      to metastatic biopsies. This study demonstrates the utility of whole-exome
      sequencing of cell-free DNA from patients with metastatic disease. cfDNA
      sequencing identified an ESR1 mutation, potentially explaining a patient's
      resistance to aromatase inhibition, and gave insight into how metastatic lesions
      differ from the primary tumor. 

PMID- 26317217
TI  - Do Insect Populations Die at Constant Rates as They Become Older? Contrasting
      Demographic Failure Kinetics with Respect to Temperature According to the Weibull
      Model.
AB  - Temperature implies contrasting biological causes of demographic aging in
      poikilotherms. In this work, we used the reliability theory to describe the
      consistency of mortality with age in moth populations and to show that
      differentiation in hazard rates is related to extrinsic environmental causes such
      as temperature. Moreover, experiments that manipulate extrinsic mortality were
      used to distinguish temperature-related death rates and the pertinence of the
      Weibull aging model. The Newton-Raphson optimization method was applied to
      calculate parameters for small samples of ages at death by estimating the maximum
      likelihoods surfaces using scored gradient vectors and the Hessian matrix. The
      study reveals for the first time that the Weibull function is able to describe
      contrasting biological causes of demographic aging for moth populations
      maintained at different temperature regimes. We demonstrate that at favourable
      conditions the insect death rate accelerates as age advances, in contrast to the
      extreme temperatures in which each individual drifts toward death in a linear
      fashion and has a constant chance of passing away. Moreover, slope of hazard
      rates shifts towards a constant initial rate which is a pattern demonstrated by
      systems which are not wearing out (e.g. non-aging) since the failure, or death,
      is a random event independent of time. This finding may appear surprising,
      because, traditionally, it was mostly thought as rule that in aging population
      force of mortality increases exponentially until all individuals have died.
      Moreover, in relation to other studies, we have not observed any typical
      decelerating aging patterns at late life (mortality leveling-off), but rather,
      accelerated hazard rates at optimum temperatures and a stabilized increase at the
      extremes.In most cases, the increase in aging-related mortality was simulated
      reasonably well according to the Weibull survivorship model that is applied.
      Moreover, semi log- probability hazard rate model illustrations and maximum
      likelihoods may be usefully in defining periods of mortality leveling off and
      provide clear evidence that environmental variability may affect parameter
      estimates and insect population failure rate. From a reliability theory
      standpoint, failure rates vary according to a linear function of age at the
      extremes indicating that the life system (i.e., population) is able to eliminate
      earlier failure and/or to keep later failure rates constant. The applied model
      was able to identify the major correlates of extended longevity and to suggest
      new ideas for using demographic concepts in both basic and applied population
      biology and aging. 

PMID- 26317218
TI  - Rb1 and Pten Co-Deletion in Osteoblast Precursor Cells Causes Rapid Lipoma
      Formation in Mice.
AB  - The Rb and Pten tumor suppressor genes are important regulators of bone
      development and both are frequently mutated in the bone cancer osteosarcoma (OS).
      To determine if Rb1 and Pten synergize as tumor suppressor genes for
      osteosarcoma, we co-deleted them in osteoprogenitor cells. Surprisingly, we
      observed rapid development of adipogenic but not osteosarcoma tumors in the
      DeltaRb1/Pten mice. DeltaPten solo deleted mice also developed lipoma tumors but
      at a much reduced frequency and later onset than those co-deleted for Rb1. Pten
      deletion also led to a marked increase in adipocytes in the bone marrow. To
      better understand the function of Pten in bone development in vivo, we
      conditionally deleted Pten in OSX(+) osteoprogenitor cells using OSX-Cre mice.
      MUCT analysis revealed a significant thickening of the calvaria and an increase
      in trabeculae volume and number in the femur, consistent with increased bone
      formation in these mice. To determine if Pten and Rb1 deletion actively promotes
      adipogenic differentiation, we isolated calvarial cells from Pten(fl/fl) and
      Pten(fl/fl); Rb1(fl/fl) mice, infected them with CRE or GFP expressing
      adenovirus, treated with differentiation media. We observed slightly increased
      adipogenic, and osteogenic differentiation in the DeltaPten cells. Both
      phenotypes were greatly increased upon Rb1/Pten co-deletion. This was accompanied
      by an increase in expression of genes required for adipogenesis. These data
      indicate that Pten deletion in osteoblast precursors is sufficient to promote
      frequent adipogenic, but only rare osteogenic tumors. Rb1 hetero- or homo-zygous
      co-deletion greatly increases the incidence and the rapidity of onset of
      adipogenic tumors, again, with only rare osteosarcoma tumors.

PMID- 26317219
TI  - Stromal Cells Derived from Visceral and Obese Adipose Tissue Promote Growth of
      Ovarian Cancers.
AB  - Obesity, and in particular visceral obesity, has been associated with an
      increased risk of developing cancers as well as higher rates of mortality
      following diagnosis. The impact of obesity on adipose-derived stromal cells
      (ASC), which contribute to the formation of tumor stroma, is unknown. Here we
      hypothesized that visceral source and diet-induced obesity (DIO) changes the ASC
      phenotype, contributing to the tumor promoting effects of obesity. We found that
      ASC isolated from subcutaneous (SC-ASC) and visceral (V-ASC) white adipose
      tissue(WAT) of lean(Le) and obese(Ob) mice exhibited similar mesenchymal cell
      surface markers expression, and had comparable effects on ovarian cancer cell
      proliferation and migration. Obese and visceral derived ASC proliferated slower
      and exhibited impaired differentiation into adipocytes and osteocytes in vitro as
      compared to ASC derived from subcutaneous WAT of lean mice. Intraperitoneal co
      injection of ovarian cancer cells with obese or visceral derived ASC, but not
      lean SC-ASC, increased growth of intraperitoneal ID8 tumors as compared to
      controls. Obese and V-ASC increased stromal infiltration of inflammatory cells,
      including CD3+ T cells and F4/80+ macrophages. Obese and visceral derived ASC,
      but not lean SC-ASC, increased expression of chemotactic factors IL-6, MIP-2, and
      MCP-1 when cultured with tumor cells. Overall, these results demonstrate that
      obese and V-ASC have a unique phenotype, with more limited proliferation and
      differentiation capacity but enhanced expression of chemotactic factors in
      response to malignant cells which support infiltration of inflammatory cells and
      support tumor growth and dissemination. 

PMID- 26317220
TI  - Correction: Modeling of In-Utero and Intra-Partum Transmissions to Evaluate the
      Efficacy of Interventions for the Prevention of Perinatal HIV.

PMID- 26317221
TI  - Helicobacter pylori bab Paralog Distribution and Association with cagA, vacA, and
      homA/B Genotypes in American and South Korean Clinical Isolates.
AB  - Helicobacter pylori genetic variation is a crucial component of colonization and
      persistence within the inhospitable niche of the gastric mucosa. As such,
      numerous H. pylori genes have been shown to vary in terms of presence and genomic
      location within this pathogen. Among the variable factors, the Bab family of
      outer membrane proteins (OMPs) has been shown to differ within subsets of
      strains. To better understand genetic variation among the bab genes and to
      determine whether this variation differed among isolates obtained from different
      geographic locations, we characterized the distribution of the Bab family members
      in 80 American H. pylori clinical isolates (AH) and 80 South Korean H. pylori
      clinical isolates (KH). Overall, we identified 23 different bab genotypes (19 in
      AH and 11 in KH), but only 5 occurred in greater than 5 isolates. Regardless of
      strain origin, a strain in which locus A and locus B were both occupied by a bab
      gene was the most common (85%); locus C was only occupied in those isolates that
      carried bab paralog at locus A and B. While the babA/babB/- genotype predominated
      in the KH (78.8%), no single genotype could account for greater than 40% in the
      AH collection. In addition to basic genotyping, we also identified associations
      between bab genotype and well known virulence factors cagA and vacA.
      Specifically, significant associations between babA at locus A and the cagA EPIYA
      ABD motif (P<0.0001) and the vacA s1/i1/m1 allele (P<0.0001) were identified. Log
      linear modeling further revealed a three-way association between bab carried at
      locus A, vacA, and number of OMPs from the HOM family (P<0.002). En masse this
      study provides a detailed characterization of the bab genotypes from two distinct
      populations. Our analysis suggests greater variability in the AH, perhaps due to
      adaptation to a more diverse host population. Furthermore, when considering the
      presence or absence of both the bab and homA/B paralogs at their given loci and
      the vacA genotype, an association was observed. Our results highlight the
      multifactorial nature of H. pylori mediated disease and the importance of
      considering how the specific combinations of H. pylori virulence genes and their
      multiple interactions with the host will collectively impact disease progression.

PMID- 26317222
TI  - Functional Organization of the Action Observation Network in Autism: A Graph
      Theory Approach.
AB  - BACKGROUND: The ability to recognize, understand and interpret other's actions
      and emotions has been linked to the mirror system or action-observation-network
      (AON). Although variations in these abilities are prevalent in the neuro-typical
      population, persons diagnosed with autism spectrum disorders (ASD) have deficits
      in the social domain and exhibit alterations in this neural network. METHOD:
      Here, we examined functional network properties of the AON using graph theory
      measures and region-to-region functional connectivity analyses of resting-state
      fMRI-data from adolescents and young adults with ASD and typical controls (TC).
      RESULTS: Overall, our graph theory analyses provided convergent evidence that the
      network integrity of the AON is altered in ASD, and that reductions in network
      efficiency relate to reductions in overall network density (i.e., decreased
      overall connection strength). Compared to TC, individuals with ASD showed
      significant reductions in network efficiency and increased shortest path lengths
      and centrality. Importantly, when adjusting for overall differences in network
      density between ASD and TC groups, participants with ASD continued to display
      reductions in network integrity, suggesting that also network-level
      organizational properties of the AON are altered in ASD. CONCLUSION: While
      differences in empirical connectivity contributed to reductions in network
      integrity, graph theoretical analyses provided indications that also changes in
      the high-level network organization reduced integrity of the AON.

PMID- 26317223
TI  - Comparison of HIV-1 nef and gag Variations and Host HLA Characteristics as
      Determinants of Disease Progression among HIV-1 Vertically Infected Kenyan
      Children.
AB  - OBJECTIVES: Disease progression varies among HIV-1-infected individuals. The
      present study aimed to explore possible viral and host factors affecting disease
      progression in HIV-1-infected children. METHODS: Since 2000, 102 HIV-1 vertically
      infected children have been followed-up in Kenya. Here we studied 29 children (15
      male/14 female) who started antiretroviral treatment at <5 years of age (rapid
      progressors; RP), and 32 (17 male/15 female) who started at >10 years of age
      (slow progressors; SP). Sequence variations in the HIV-1 gag and nef genes and
      the HLA class I-related epitopes were compared between the two groups. RESULTS:
      Based on nef sequences, HIV-1 subtypes A1/D were detected in 62.5%/12.5% of RP
      and 66.7%/20% of SP, with no significant difference in subtype distribution
      between groups (p = 0.8). In the ten Nef functional domains, only the PxxP3
      region showed significantly greater variation in RP (33.3%) than SP (7.7%, p =
      0.048). Gag sequences did not significantly differ between groups. The reportedly
      protective HLA-A alleles, A*74:01, A*32:01 and A*26, were more commonly observed
      in SP (50.0%) than RP (11.1%, p = 0.010), whereas the reportedly disease
      susceptible HLA-B*45:01 was more common in RP (33.3%) than SP (7.4%, p = 0.045).
      Compared to RP, SP showed a significantly higher median number of predicted HLA-B
      related 12-mer epitopes in Nef (3 vs. 2, p = 0.037), HLA-B-related 11-mer
      epitopes in Gag (2 vs. 1, p = 0.029), and HLA-A-related 9-mer epitopes in Gag (4
      vs. 1, p = 0.051). SP also had fewer HLA-C-related epitopes in Nef (median 4 vs.
      5, p = 0.046) and HLA-C-related 11-mer epitopes in Gag (median 1 vs. 1.5, p =
      0.044) than RP. CONCLUSIONS: Compared to rapid progressors, slow progressors had
      more protective HLA-A alleles and more HLA-B-related epitopes in both the Nef and
      Gag proteins. These results suggest that the host factor HLA plays a stronger
      role in disease progression than the Nef and Gag sequence variations in HIV-1
      infected Kenyan children.

PMID- 26317224
TI  - INF-gamma Enhances Nox2 Activity by Upregulating phox Proteins When Applied to
      Differentiating PLB-985 Cells but Does Not Induce Nox2 Activity by Itself.
AB  - BACKGROUND: The cytokine and drug interferon-gamma enhances superoxide anion
      production by the antimicrobicidal Nox2 enzyme of neutrophils. Because mature
      neutrophils have a short lifespan, we hypothesized that the effects of interferon
      gamma on these cells might be mediated by its prolonged exposure to
      differentiating neutrophil precursors in the bone marrow rather than its brief
      exposure to mature circulating neutrophils. Effects of INF-Gamma on NOX2
      activity: To address this possibility we exposed the myeloid PLB-985 cell line to
      interferon-gamma for 3 days in the presence of dimethyl sulfoxide which induces
      terminal differentiation of these cells. Interferon-gamma was found to enhance
      superoxide production by Nox2 in a concentration dependent manner. In contrast,
      application of interferon-gamma alone for 3 days failed to induce detectible Nox2
      activity. Additionally, application of interferon-gamma for 3 hours to pre
      differentiated PLB-985 cells, which models studies using isolated neutrophils,
      was much less effective at enhancing superoxide anion production. Effects of INF
      Gamma on phox protein levels: Addition of interferon-gamma during differentiation
      was found to upregulate the Nox2 proteins gp91phox and p47phox in concert with
      elevated transcription of their genes. The p22phox protein was upregulated in the
      absence of increased transcription presumably reflecting stabilization resulting
      from binding to the elevated gp91phox. Thus, increased levels of gp91phox,
      p47phox and p22phox likely account for the interferon-gamma mediated enhancement
      of dimethyl sulfoxide-induced Nox2 activity. In contrast, although interferon
      gamma alone also increased various phox proteins and their mRNAs, the pattern was
      very different to that seen with interferon-gamma plus dimethyl sulfoxide. In
      particular, p47phox was not induced thus explaining the inability of interferon 
      gamma alone to enhance Nox2 activity. Short application of interferon-gamma to
      already differentiated cells failed to increase any phox proteins. CONCLUSIONS:
      Our findings indicate that interferon-gamma has complex effects on phox protein
      expression and that these are different in cells undergoing terminal
      differentiation. Understanding these changes may indicate additional therapeutic
      uses for this cytokine in human disorders.

PMID- 26317225
TI  - Dominance of Deleterious Alleles Controls the Response to a Population
      Bottleneck.
AB  - Population bottlenecks followed by re-expansions have been common throughout
      history of many populations. The response of alleles under selection to such
      demographic perturbations has been a subject of great interest in population
      genetics. On the basis of theoretical analysis and computer simulations, we
      suggest that this response qualitatively depends on dominance. The number of
      dominant or additive deleterious alleles per haploid genome is expected to be
      slightly increased following the bottleneck and re-expansion. In contrast, the
      number of completely or partially recessive alleles should be sharply reduced.
      Changes of population size expose differences between recessive and additive
      selection, potentially providing insight into the prevalence of dominance in
      natural populations. Specifically, we use a simple statistic, [Formula: see
      text], where xi represents the derived allele frequency, to compare the number of
      mutations in different populations, and detail its functional dependence on the
      strength of selection and the intensity of the population bottleneck. We also
      provide empirical evidence showing that gene sets associated with autosomal
      recessive disease in humans may have a BR indicative of recessive selection.
      Together, these theoretical predictions and empirical observations show that
      complex demographic history may facilitate rather than impede inference of
      parameters of natural selection. 

PMID- 26317226
TI  - Increased MU-Calpain Activity in Blasts of Common B-Precursor Childhood Acute
      Lymphoblastic Leukemia Correlates with Their Lower Susceptibility to Apoptosis.
AB  - Childhood acute lymphoblastic leukemia (ALL) blasts are characterized by
      inhibited apoptosis promoting fast disease progress. It is known that in chronic
      lymphocytic and acute myeloid leukemias the reduced apoptosis is strongly related
      with the activity of calpain-calpastatin system (CCS) composed of cytoplasmic
      proteases--calpains--performing the modulatory proteolysis of key proteins
      involved in cell proliferation and apoptosis, and of their endogenous inhibitor-
      calpastatin. Here, the CCS protein abundance and activity was for the first time
      studied in childhood ALL blasts and in control bone marrow CD19+ B cells by semi
      quantitative flow cytometry and western blotting of calpastatin fragments
      resulting from endogenous calpain activity. Significantly higher MU-calpain
      (CAPN1) gene transcription, protein amounts and activity (but not those of m
      calpain), with calpastatin amount and transcription of its gene (CAST) greatly
      varying were observed in CD19(+) ALL blasts compared to control cells.
      Significant inverse relation between the amount/activity of calpain and
      spontaneous apoptosis was noted. Patients older than 10 years (considered at
      higher risk) displayed increased amounts and activities of blast calpain.
      Finally, treatment of blasts with the tripeptide calpain inhibitors II and IV
      significantly and in dose-dependent fashion increased the percentage of blasts
      entering apoptosis. Together, these findings make the CCS a potential new
      predictive tool and therapeutic target in childhood ALL.

PMID- 26317227
TI  - What Data to Use for Forest Conservation Planning? A Comparison of Coarse Open
      and Detailed Proprietary Forest Inventory Data in Finland.
AB  - The boreal region is facing intensifying resource extraction pressure, but the
      lack of comprehensive biodiversity data makes operative forest conservation
      planning difficult. Many countries have implemented forest inventory schemes and
      are making extensive and up-to-date forest databases increasingly available. Some
      of the more detailed inventory databases, however, remain proprietary and
      unavailable for conservation planning. Here, we investigate how well different
      open and proprietary forest inventory data sets suit the purpose of conservation
      prioritization in Finland. We also explore how much priorities are affected by
      using the less accurate but open data. First, we construct a set of indices for
      forest conservation value based on quantitative information commonly found in
      forest inventories. These include the maturity of the trees, tree species
      composition, and site fertility. Secondly, using these data and accounting for
      connectivity between forest types, we investigate the patterns in conservation
      priority. For prioritization, we use Zonation, a method and software for spatial
      conservation prioritization. We then validate the prioritizations by comparing
      them to known areas of high conservation value. We show that the overall priority
      patterns are relatively consistent across different data sources and analysis
      options. However, the coarse data cannot be used to accurately identify the high
      priority areas as it misses much of the fine-scale variation in forest
      structures. We conclude that, while inventory data collected for forestry
      purposes may be useful for forest conservation purposes, it needs to be detailed
      enough to be able to account for more fine-scaled features of high conservation
      value. These results underline the importance of making detailed inventory data
      publicly available. Finally, we discuss how the prioritization methodology we
      used could be integrated into operative forest management, especially in
      countries in the boreal zone. 

PMID- 26317228
TI  - HLA Class I and Class II Alleles and Haplotypes Confirm the Berber Origin of the
      Present Day Tunisian Population.
AB  - In view of its distinct geographical location and relatively small area, Tunisia
      witnessed the presence of many civilizations and ethnic groups throughout
      history, thereby questioning the origin of present-day Tunisian population. We
      investigated HLA class I and class II gene profiles in Tunisians, and compared
      this profile with those of Mediterranean and Sub-Sahara African populations. A
      total of 376 unrelated Tunisian individuals of both genders were genotyped for
      HLA class I (A, B) and class II (DRB1, DQB1), using reverse dot-blot
      hybridization (PCR-SSO) method. Statistical analysis was performed using Arlequin
      software. Phylogenetic trees were constructed by DISPAN software, and
      correspondence analysis was carried out by VISTA software. One hundred fifty
      three HLA alleles were identified in the studied sample, which comprised 41, 50,
      40 and 22 alleles at HLA-A,-B,-DRB1 and -DQB1 loci, respectively. The most
      frequent alleles were HLA-A*02:01 (16.76%), HLA-B*44:02/03 (17.82%), HLA
      DRB1*07:01 (19.02%), and HLA-DQB1*03:01 (17.95%). Four-locus haplotype analysis
      identified HLA-A*02:01-B*50:01-DRB1*07:01-DQB1*02:02 (2.2%) as the common
      haplotype in Tunisians. Compared to other nearby populations, Tunisians appear to
      be genetically related to Western Mediterranean population, in particular North
      Africans and Berbers. In conclusion, HLA genotype results indicate that Tunisians
      are related to present-day North Africans, Berbers and to Iberians, but not to
      Eastern Arabs (Palestinians, Jordanians and Lebanese). This suggests that the
      genetic contribution of Arab invasion of 7th-11th century A.D. had little impact
      of the North African gene pool. 

PMID- 26317229
TI  - The Utility of the Memorable Messages Framework as an Intermediary Evaluation
      Tool for Fruit and Vegetable Consumption in a Nutrition Education Program.
AB  - Additional strategies to evaluate the impact of community nutrition education
      programs on low-income individuals are needed. The objective of this qualitative
      study was to examine the use of the Memorable Messages Framework as an
      intermediary nutrition education program evaluation tool to determine what fruit
      and vegetable messages were reported as memorable and the characteristics of
      those memorable messages. A convenience sample of low-income, primarily African
      American adults (N = 58) who previously completed a series of community nutrition
      education lessons within an urban area of Indiana participated in a focus group
      (N = 8 focus groups). A lead moderator using a semistructured script conducted
      the focus groups to determine what information about fruits and vegetables was
      most memorable from the participants' nutrition lessons and why this information
      was memorable. All focus group audiotapes were transcribed verbatim and ATLAS.ti
      software was used to code and identify themes within the data. Participants cited
      quantity, variety, and the positive nutritional impact of eating fruits and
      vegetables as most memorable. Information given in the form of recipes was also
      cited as most memorable. For example, participants referred to the recipe
      demonstrations as not only fun but also key components of the program that helped
      with message retention and memorability. Key characteristics of memorable
      messages included personal relevance and message vividness. These findings
      indicated that the Memorable Messages Framework may serve as an intermediary
      program evaluation tool to identify what information and messages are most
      influential to participants in community nutrition education programs.

PMID- 26317230
TI  - Extent of Spine Deformity Predicts Lung Growth and Function in Rabbit Model of
      Early Onset Scoliosis.
AB  - Early onset deformity of the spine and chest wall (initiated <8 years of age) is
      associated with increased morbidity at adulthood relative to adolescent onset
      deformity of comparable severity. Presumably, inhibition of thoracic growth
      during late stage alveolarization leads to an irreversible loss of pulmonary
      growth and thoracic function; however the natural history of this disease from
      onset to adulthood has not been well characterized. In this study we establish a
      rabbit model of early onset scoliosis to establish the extent that thoracic
      deformity affects structural and functional respiratory development. Using a
      surgical right unilateral rib-tethering procedure, rib fusion with early onset
      scoliosis was induced in 10 young New Zealand white rabbits (3 weeks old).
      Progression of spine deformity, functional residual capacity, total lung
      capacity, and lung mass was tracked through longitudinal breath-hold computed
      tomography imaging up to skeletal maturity (28 weeks old). Additionally at
      maturity forced vital capacity and regional specific volume were calculated as
      functional measurements and histo-morphometry performed with the radial alveolar
      count as a measure of acinar complexity. Data from tethered rib rabbits were
      compared to age matched healthy control rabbits (N = 8). Results show unilateral
      rib-tethering created a progressive spinal deformity ranging from 30 degrees  to
      120 degrees  curvature, the severity of which was strongly associated with
      pulmonary growth and functional outcomes. At maturity rabbits with deformity
      greater than the median (55 degrees ) had decreased body weight (89%), right
      (59%) and left (86%) lung mass, right (74%) and left (69%) radial alveolar count,
      right lung volume at total lung capacity (60%), and forced vital capacity (75%).
      Early treatment of spinal deformity in children may prevent pulmonary
      complications in adulthood and these results provide a basis for the prediction
      of pulmonary development from thoracic structure. This model may also have future
      use as a platform to evaluate treatment effectiveness. 

PMID- 26317231
TI  - Evidence for the in vitro bioactivation of aminopyrazole derivatives: trapping
      reactive aminopyrazole intermediates using glutathione ethyl ester in human liver
      microsomes.
AB  - Drug-induced toxicity is a leading cause of drug withdrawal from clinical
      development and clinical use and represents a major impediment to the development
      of new drugs. The mechanisms underlying drug-induced toxicities are varied;
      however, metabolic bioactivation to form reactive metabolites has been identified
      as a major contributor.1,2 These electrophilic species can covalently modify
      important biological macromolecules and thereby increase the risk of adverse drug
      reactions or idiosyncratic toxicity. Consequently, screening compounds for their
      propensity to form reactive metabolites has become an integral part of drug
      discovery programs. This screening process typically involves identification of
      structural alerts as well as the generation of reactive metabolites in vitro in
      subcellular hepatic fractions, followed by trapping the reactive species with
      nucleophiles and characterization via LC-MS. This article presents evidence for
      the bioactivation of a series of aminopyrazole derivatives via LC-MS detection of
      glutathione ethyl ester-trapped reactive intermediates formed in human liver
      microsomal incubations. These results indicate that the aminopyrazole motif,
      within specific contexts, may be considered a new structural alert for the
      potential formation of reactive metabolites. 

PMID- 26317232
TI  - IDO-GCN2 and autophagy in inflammation.

PMID- 26317233
TI  - Validating subcellular thermal changes revealed by fluorescent thermosensors.

PMID- 26317234
TI  - The 10(5) gap issue between calculation and measurement in single-cell
      thermometry.

PMID- 26317235
TI  - Reply to: "Validating subcellular thermal changes revealed by fluorescent
      thermosensors" and "The 10(5) gap issue between calculation and measurement in
      single-cell thermometry".

PMID- 26317236
TI  - Mapping proteins with spatial proteomics.

PMID- 26317237
TI  - Removing roadblocks to deep sequencing of modified RNAs.

PMID- 26317238
TI  - Conformations and Conformational Processes of Hexahydrobenzazocines by NMR and
      DFT Studies.
AB  - Conformational processes that occur in hexahydrobenzazocines have been studied
      with the (1)H and (13)C dynamic nuclear magnetic resonance (DNMR) spectroscopy.
      The coalescence effects are assigned to two different conformational processes:
      the ring-inversion of the ground-state conformations and the interconversion
      between two different conformers. The barriers for these processes are in the
      range of 42-52 and 42-43 kJ mol(-1), respectively. Molecular modeling on the
      density functional theory (DFT) level and the gauge invariant atomic orbitals
      (GIAO)-DFT calculations of isotropic shieldings and coupling constants for the
      set of low-energy conformations were compared with the experimental NMR data. The
      ground-state of all compounds in solution is the boat-chair (BC) conformation.
      The BC form adopts two different conformations because the nitrogen atom can be
      in the boat or chair parts of the BC structure. These two conformers are engaged
      in the interconversion process. 

PMID- 26317239
TI  - Ag/BiOBr Film in a Rotating-Disk Reactor Containing Long-Afterglow Phosphor for
      Round-the-Clock Photocatalysis.
AB  - Ag/BiOBr film coated on the glass substrate was synthesized by a solvothermal
      method and a subsequent photoreduction process. Such a Ag/BiOBr film was then
      adhered to a hollow rotating disk filled with long-afterglow phosphor inside the
      chamber. The Ag/BiOBr film exhibited high photocatalytic activity for organic
      pollutant degradation owing to the improved visible-light harvesting and the
      separation of photoinduced charges. The long-afterglow phosphor could absorb the
      excessive daylight and emit light around 488 nm, activating the Ag/BiOBr film to
      realize round-the-clock photocatalysis. Because the Ag nanoparticles could extend
      the light absorbance of the Ag/BiOBr film to wavelengths of around 500 nm via a
      surface plasma resonance effect, they played a key role in realizing
      photocatalysis induced by long-afterglow phosphor. 

PMID- 26317240
TI  - Direct Growth of Single- and Few-Layer MoS2 on h-BN with Preferred Relative
      Rotation Angles.
AB  - Monolayer molybdenum disulfide (MoS2) is a promising two-dimensional direct
      bandgap semiconductor with potential applications in atomically thin and flexible
      electronics. An attractive insulating substrate or mate for MoS2 (and related
      materials such as graphene) is hexagonal boron nitride (h-BN). Stacked
      heterostructures of MoS2 and h-BN have been produced by manual transfer methods,
      but a more efficient and scalable assembly method is needed. Here we demonstrate
      the direct growth of single- and few-layer MoS2 on h-BN by chemical vapor
      deposition (CVD) method, which is scalable with suitably structured substrates.
      The growth mechanisms for single-layer and few-layer samples are found to be
      distinct, and for single-layer samples low relative rotation angles (<5 degrees )
      between the MoS2 and h-BN lattices prevail. Moreover, MoS2 directly grown on h-BN
      maintains its intrinsic 1.89 eV bandgap. Our CVD synthesis method presents an
      important advancement toward controllable and scalable MoS2-based electronic
      devices. 

PMID- 26317241
TI  - Surface-Activated Coupling Reactions Confined on a Surface.
AB  - Chemical reactions may take place in a pure phase of gas or liquid or at the
      interface of two phases (gas-solid or liquid-solid). Recently, the emerging field
      of "surface-confined coupling reactions" has attracted intensive attention. In
      this process, reactants, intermediates, and products of a coupling reaction are
      adsorbed on a solid-vacuum or a solid-liquid interface. The solid surface
      restricts all reaction steps on the interface, in other words, the reaction takes
      place within a lower-dimensional, for example, two-dimensional, space. Surface
      atoms that are fixed in the surface and adatoms that move on the surface often
      activate the surface-confined coupling reactions. The synergy of surface
      morphology and activity allow some reactions that are inefficient or prohibited
      in the gas or liquid phase to proceed efficiently when the reactions are confined
      on a surface. Over the past decade, dozens of well-known "textbook" coupling
      reactions have been shown to proceed as surface-confined coupling reactions. In
      most cases, the surface-confined coupling reactions were discovered by trial and
      error, and the reaction pathways are largely unknown. It is thus highly desirable
      to unravel the mechanisms, mechanisms of surface activation in particular, of the
      surface-confined coupling reactions. Because the reactions take place on
      surfaces, advanced surface science techniques can be applied to study the surface
      confined coupling reactions. Among them, scanning tunneling microscopy (STM) and
      X-ray photoelectron spectroscopy (XPS) are the two most extensively used
      experimental tools. The former resolves submolecular structures of individual
      reactants, intermediates, and products in real space, while the latter monitors
      the chemical states during the reactions in real time. Combination of the two
      methods provides unprecedented spatial and temporal information on the reaction
      pathways. The experimental findings are complemented by theoretical modeling. In
      particular, density-functional theory (DFT) transition-state calculations have
      been used to shed light on reaction mechanisms and to unravel the trends of
      different surface materials. In this Account, we discuss recent progress made in
      two widely studied surface-confined coupling reactions, aryl-aryl (Ullmann-type)
      coupling and alkyne-alkyne (Glaser-type) coupling, and focus on surface
      activation effects. Combined experimental and theoretical studies on the same
      reactions taking place on different metal surfaces have clearly demonstrated that
      different surfaces not only reduce the reaction barrier differently and render
      different reaction pathways but also control the morphology of the reaction
      products and, to some degree, select the reaction products. We end the Account
      with a list of questions to be addressed in the future. Satisfactorily answering
      these questions may lead to using the surface-confined coupling reactions to
      synthesize predefined products with high yield. 

PMID- 26317242
TI  - Influence of Shear Stress on Cationic Surfactant Uptake by Anionic Gels.
AB  - Kinetic studies of cationic surfactant uptake by anionic polymer gel membrane
      under various shear flow have been performed, varying the alkyl chain length of
      surfactant, the ionic strength of surfactant solution, and the charge density of
      gel. By exposing the gel surface to a shear flow of ca. 1 Pa, the rate of
      surfactant uptake is distinctly enhanced, while the maximum binding ratio to the
      gel is not influenced. A linear relationship between the surfactant initial flux
      and shear stress has been established. At a high ionic strength, the effect of
      shear stress is suppressed, suggesting that the enhancement of surfactant uptake
      under shear flow is caused by a decrease in the surface electrostatic potential
      of the negatively charged polyelectrolyte gel, which favors the uptake of the
      positively charged surfactant. From the Nernst and Planck equation, a
      relationship between the surfactant uptake kinetics and the electrostatic field
      is derived that allows us to estimate the shear stress dependence of the change
      in the electrostatic field on the gel surface. The origin of the shear-induced
      surface electrostatic field change is discussed. 

PMID- 26317244
TI  - Thermal Desorption Spectroscopy Study of the Adsorption and Reduction of NO by
      Cobalt Cluster Ions under Thermal Equilibrium Conditions at 300 K.
AB  - Adsorption of NO molecules on gas phase cobalt cluster ions, Con(+) (n = 4-9),
      was investigated in thermal equilibrium with He gas at 300 K. The Con(+)
      clusters, contrary to the isolated clusters in a vacuum, adsorbed NO without
      undergoing significant dissociation. Thermal desorption spectroscopy of
      Con(+)(NO)m indicated that Con(+) clusters with n = 4-6 and n = 7-9 can have four
      and six adatoms chemisorbed, respectively. Reduction of NO occurred, releasing N2
      molecules, to form Con(+)Ok(NO)m-k (k = 2, 4, ...). The reaction mechanism
      involved the exchange of chemisorbed N atoms with the O atom in NO bound to the
      clusters. The reactivity of Con(+) (n = 4-9) exhibited periodic n dependence, and
      Co6(+) and Co9(+) was similar to the case of the isolated Co16(+) clusters
      holding up to eight adatoms reported by Anderson et al. ( J. Chem. Phys . 2009 ,
      130 , 10992 - 11000 ). 

PMID- 26317243
TI  - P-glycoprotein, CYP3A, and Plasma Carboxylesterase Determine Brain Disposition
      and Oral Availability of the Novel Taxane Cabazitaxel (Jevtana) in Mice.
AB  - We aimed to clarify the roles of the multidrug-detoxifying proteins ABCB1, ABCG2,
      ABCC2, and CYP3A in oral availability and brain accumulation of cabazitaxel, a
      taxane developed for improved therapy of docetaxel-resistant prostate cancer.
      Cabazitaxel pharmacokinetics were studied in Abcb1a/1b, Abcg2, Abcc2, Cyp3a, and
      combination knockout mice. We found that human ABCB1, but not ABCG2, transported
      cabazitaxel in vitro. Upon oral cabazitaxel administration, total plasma levels
      were greatly increased due to binding to plasma carboxylesterase Ces1c, which is
      highly upregulated in several knockout strains. Ces1c inhibition and in vivo
      hepatic Ces1c knockdown reversed these effects. Correcting for Ces1c effects,
      Abcb1a/1b, Abcg2, and Abcc2 did not restrict cabazitaxel oral availability,
      whereas Abcb1a/1b, but not Abcg2, dramatically reduced cabazitaxel brain
      accumulation (>10-fold). Coadministration of the ABCB1 inhibitor elacridar
      completely reversed this brain accumulation effect. After correction for Ces1c
      effects, Cyp3a knockout mice demonstrated a strong (six-fold) increase in
      cabazitaxel oral availability, which was completely reversed by transgenic human
      CYP3A4 in intestine and liver. Cabazitaxel markedly inhibited mouse Ces1c, but
      human CES1 and CES2 only weakly. Ces1c upregulation can thus complicate
      preclinical cabazitaxel studies. In summary, ABCB1 limits cabazitaxel brain
      accumulation and therefore potentially therapeutic efficacy against
      (micro)metastases or primary tumors positioned wholly or partly behind a
      functional blood-brain barrier. This can be reversed with elacridar
      coadministration, and similar effects may apply to ABCB1-expressing tumors.
      CYP3A4 profoundly reduces the oral availability of cabazitaxel. This may
      potentially be greatly improved by coadministering ritonavir or other CYP3A
      inhibitors, suggesting the option of patient-friendly oral cabazitaxel therapy. 

PMID- 26317245
TI  - Characterization and Multilineage Differentiation of Domestic and Black-Footed
      Cat Mesenchymal Stromal/Stem Cells from Abdominal and Subcutaneous Adipose
      Tissue.
AB  - Transplantation of mesenchymal stem cells (MSCs) isolated from bone marrow or
      adipose tissue is emerging as a promising tool for cell replacement therapy and
      regenerative medicine in domestic and endangered animal species. Defining the
      differentiation capability of adipose-derived mesenchymal stromal/stem cells
      (AMSCs) collected from different depot sites of adipose tissue will be essential
      for developing strategies for cell replacement therapy. In the present study, we
      compared the biological characteristics of domestic cat AMSCs isolated from
      visceral fat of the abdominal cavity (AB) with AMSCs from subcutaneous (SQ)
      tissue, and the functional capability of domestic and black-footed cat (Felis
      nigripes) AMSCs to differentiate into other cell types. Our results showed that
      both domestic and black-footed cat adipose-derived stromal vascular fractions
      contained AMSCs. Both domestic cat AB- and SQ-AMSCs showed important clonogenic
      ability and the minimal MSC immunophenotype as defined by the International
      Society for Cellular Therapy in humans. However, domestic cat AB-AMSCs had higher
      percentages of cells positive for MSCs-associated cluster of differentiation (CD)
      markers CD90(+) and CD105(+) (92% and 80%, respectively) than those of SQ-AMSCs
      (77% and 58%, respectively). Although these results may suggest that AB-AMSCs may
      be more multipotent than SQ-AMSCs, both types of cells showed similar expression
      of pluripotent genes Oct-4 and Klf4, except for higher expression of Nanog than
      in AB-AMSCs, and equivalent in vitro multilineage differentiation. Under
      appropriate stimuli, the black-footed cat and both domestic cat AB- and SQ-AMSCs
      differentiated not only toward mesoderm cell lineages but also toward ectoderm
      cell lineage, such as neuron cell-like cells. Black-footed cat AMSCs had more
      capability to differentiate toward chondrocytes. These results suggest that the
      defined AMSC population (regardless of site of collection) could potentially be
      employed as a therapeutic agent for both domestic and endangered diseased or
      injured felids. 

PMID- 26317246
TI  - Association of CFHR1 homozygous deletion with acute myelogenous leukemia in the
      European population.

PMID- 26317249
TI  - Exploration-exploitation: A cognitive dilemma still unresolved.
AB  - The solution to the exploration-exploitation dilemma presented essentially
      subsumes exploitation into an information-maximizing model. Such a single
      maximization model is shown to be (1) more tractable than the initial dual
      maximization dilemma, (2) useful in modeling information-maximizing subsystems,
      and (3) profitably applied in artificial simulations where exploration is
      costless. However, the model fails to resolve the dilemma in ethological or
      practical circumstances with objective outcomes, such as inclusive fitness,
      rather than information outcomes, such as lack of surprise. 

PMID- 26317248
TI  - Association Between Prediagnostic Serum 25-Hydroxyvitamin D Concentration and
      Glioma.
AB  - There are no previous studies of the association between prediagnostic serum
      vitamin D concentration and glioma. Vitamin D has immunosuppressive properties;
      as does glioma. It was, therefore, our hypothesis that elevated vitamin D
      concentration would increase glioma risk. We conducted a nested case-control
      study using specimens from the Janus Serum Bank cohort in Norway. Blood donors
      who were subsequently diagnosed with glioma (n = 592), between 1974 and 2007,
      were matched to donors without glioma (n = 1112) on date and age at blood
      collection and sex. We measured 25-hydroxyvitamin D [25(OH)D], an indicator of
      vitamin D availability, using liquid chromatography coupled with mass
      spectrometry. Seasonally adjusted odds ratios (ORs) and 95% confidence intervals
      (95% CIs) were estimated for each control quintile of 25(OH)D using conditional
      logistic regression. Among men diagnosed with high grade glioma >56, we found a
      negative trend (P = .04). Men diagnosed <= 56 showed a borderline positive trend
      (P = .08). High levels (>66 nmol/L) of 25(OH)D in men >56 were inversely related
      to high grade glioma from >=2 yr before diagnosis (OR = 0.59; 95% CI = 0.38,
      0.91) to >=15 yr before diagnosis (OR = 0.61; 95% CI = 0.38,0.96). Our findings
      are consistent long before glioma diagnosis and are therefore unlikely to reflect
      preclinical disease.

PMID- 26317251
TI  - Endovascular revascularization in patients with acute obstructive mesenteric
      ischemia.

PMID- 26317250
TI  - Autophagy is involved in ethanol-induced cardia bifida during chick
      cardiogenesis.
AB  - Excess alcohol consumption during pregnancy has been acknowledged to increase the
      incidence of congenital disorders, especially the cardiovascular system. However,
      the mechanism involved in ethanol-induced cardiac malformation in prenatal fetus
      is still unknown. We demonstrated that ethanol exposure during gastrulation in
      the chick embryo increased the incidence of cardia bifida. Previously, we
      reported that autophagy was involved in heart tube formation. In this context, we
      demonstrated that ethanol exposure increased ATG7 and LC3 expression. mTOR was
      found to be inhibited by ethanol exposure. We activated autophagy using exogenous
      rapamycin (RAPA) and observed that it induced cardiac bifida and increased GATA5
      expression. RAPA beads implantation experiments revealed that RAPA restricted
      ventricular myosin heavy chain (VMHC) expression. In vitro explant cultures of
      anterior primitive streak demonstrated that both ethanol and RAPA treatments
      could reduce cell differentiation and the spontaneous beating of cardiac
      precursor cells. In addition, the bead experiments showed that RAPA inhibited
      GATA5 expression during heart tube formation. Semiquantitative RT-PCR analysis
      indicated that BMP2 expression was increased while GATA4 expression was
      suppressed. In the embryos exposed to excess ethanol, BMP2, GATA4 and FGF8
      expression was repressed. These genes are associated with cardiomyocyte
      differentiation, while heart tube fusion is associated with increased Wnt3a but
      reduced VEGF and Slit2 expression. Furthermore, the ethanol exposure also caused
      the production of excess ROS, which might damage the cardiac precursor cells of
      developing embryos. In sum, our results revealed that disrupting autophagy and
      excess ROS generation are responsible for inducing abnormal cardiogenesis in
      ethanol-treated chick embryos. 

PMID- 26317252
TI  - Moving beyond the "LDL hypothesis".
AB  - The term "LDL hypothesis" is frequently used to describe the association of low
      density lipoprotein cholesterol (LDL-cholesterol, LDL-C) and cardiovascular (CV)
      events. Recent data from genetic studies prove a causal relation between serum
      LDL-C and CV events. These data are in agreement with mechanistic molecular
      studies and epidemiology. New randomised clinical trial data show that LDL-C
      lowering with statins and a non-statin drug, ezetimibe, reduces CV events. We
      therefore believe that the "LDL-hypothesis" has been proven; the term appears to
      be outdated and should be replaced by "LDL causality".

PMID- 26317253
TI  - Markers of arterial stiffness in peripheral arterial disease.
AB  - Increased arterial stiffness results from reduced elasticity of the arterial wall
      and is an independent predictor for cardiovascular risk. The gold standard for
      assessment of arterial stiffness is the carotid-femoral pulse wave velocity.
      Other parameters such as central aortic pulse pressure and aortic augmentation
      index are indirect, surrogate markers of arterial stiffness, but provide
      additional information on the characteristics of wave reflection. Peripheral
      arterial disease (PAD) is characterised by its association with systolic
      hypertension, increased arterial stiffness, disturbed wave reflexion and
      prognosis depending on ankle-brachial pressure index. This review summarises the
      physiology of pulse wave propagation and reflection and its changes due to aging
      and atherosclerosis. We discuss different non-invasive assessment techniques and
      highlight the importance of the understanding of arterial pulse wave analysis for
      each vascular specialist and primary care physician alike in the context of PAD. 

PMID- 26317254
TI  - Abdominal aortic aneurysm, arterial stiffening and the role of the intraluminal
      thrombus.
AB  - BACKGROUND: Measure of arterial stiffness could be affected by the presence of
      abdominal aortic aneurysm (AAA) and especially an intraluminal thrombus (ILT).
      We, therefore, sought to study this possible connection by measuring pulse wave
      velocity (PWV) and pulse wave analysis (PWA) including augmentation index
      adjusted to heart rate 75 (Aix75) in patients with AAA +/- ILT. PATIENTS AND
      METHODS: PWV and PWA were measured in male patients with AAA from an ongoing
      Danish AAA screening trial. Information on blood pressure, medications, BMI and
      smoking status was obtained at inclusion. RESULTS: In total, 157 patients were
      included. Mean age was 73 years. Mean AAA size was 42.2 mm. Fifty-six of the
      patients had an intraluminal thrombus, and patients with AAA and ILT had a
      significantly higher Aix75 than patients with AAA but without ILT (Mean = 28.3 +/
      1.4 SEM vs. 24.9 +/- 0.81, p=0.027), a difference that was also significant when
      adjusting for AAA size, blood pressure and age. There was no difference in PWV
      between the groups. CONCLUSIONS: Haemodynamic properties of the aorta are
      affected by the presence of ILT in patients with AAA that is not explained by
      aortic size. Alternatively, these findings could be explained by associations
      between ILT and properties of the left ventricle.

PMID- 26317255
TI  - Comparison of two devices for measuring exercise transcutaneous oxygen pressures
      in patients with claudication.
AB  - BACKGROUND: We aimed at estimating the agreement between the Medicap" (photo
      optical) and Radiometer* (electrochemical) sensors during exercise transcutaneous
      oxygen pressure ( tcp02) tests. Our hypothesis was that although absolute
      starting values (tcp02rest: mean over 2 minutes) might)e different, tcpOTchanges
      over time and the minimal value of the decrease from rest of oxygen pressure
      (DROPmin) results at exercise shall be concordant between the two systems.
      taneously, one of each system on the chest, on each buttock and on each calf.
      RESULTS: Seventeen Medicap" probes disconnected during the tests. tcp02rest and
      DROPmin values were higher with Medicap* than with Radiometer*, by 13.7 +/-
      17.1mmHg and 3.4 +/- 11.7 mmHg, respectively. Despite the differences in absolute
      starting values, changes over time were similar between the two systems. The
      concordance between the two systems was approximately 70% for classification of
      test results from DROPmin. CONCLUSIONS: Photo-optical sensors are promising
      alternatives to electro-chemical sensors for exercise oximetry, provided that
      miniaturization and weight reduction of the new sensors are possible. PATIENTS
      AND METHODS: Forty seven patients with arterial claudication ( 65 +/- 7 years)
      performed a treadmill test with 5 probes each of the electro-chemical and photo
      optical devices simul-

PMID- 26317256
TI  - Outcome of endovascular revascularisation in patients with acute obstructive
      mesenteric ischaemia - a single-centre experience.
AB  - BACKGROUND: Acute embolic or thrombotic mesenteric ischaemia (AMI) is a rare but
      life-threatening clinical condition. Despite diagnostic and therapeutic advances,
      the mortality rate remains high, between 60 % and 90 %. Over the last years
      revascularisation was increasingly performed by endovascular techniques. The aim
      of this study was to retrospectively analyse the clinical outcome of catheter
      directed thrombolysis (CDT) and aspiration thrombectomy (AT) in patients with AMI
      with regard to technical success, intervention-related complication rate, need
      for secondary abdominal surgery, clinical course and 30-day mortality rate.
      PATIENTS AND METHODS: Thirteen patients (4 men, 9 women; mean age 74.5 +/- 17
      years) with 12 embolic and one thrombotic occlusion of the superior mesenteric
      artery (SMA) underwent emergent endovascular revascularisation of SMA. Clinical
      data including all imaging reports, laboratory analysis and follow-up data were
      derived from the electronic patient file and images were reviewed on a Picture
      Archiving and Communication System. RESULTS: Eleven patients (n = 11; 84.6 %)
      underwent CDT and AT, and two patients (n = 2; 15.4 %) had AT alone. Technical
      success with complete restoration of SMA perfusion was achieved in 38.5 % (n =
      5). Adjunctive angioplasty +/- stenting was mandatory in 2 patients. Overall, the
      intervention-related complication rate was 38.5 %. In total, 46.2 % (n = 6)
      clinically improved following the intervention, while 38.5 % required explorative
      laparotomy after the intervention, with 2 colectomies and 2 small bowel
      resections. Overall, the 30-day mortality rate was 30.8 %. CONCLUSIONS:
      Endovascular revascularisation with CDT in combination with AT is feasible, with
      a technical success rate of 38.5 % (n = 5). Endovascular revascularisation was
      beneficial for 46.2 % (n = 6) of the patients, who clinically improved following
      the intervention. The need for secondary explorative laparotomy was rather low,
      with 38.5 % (n = 5) of the patients. The 30-day-mortality remains high with 30.8
      %.

PMID- 26317257
TI  - A prospective multicentre study on the treatment of cardiovascular risk factors
      and claudication symptoms in patients with peripheral artery disease (the
      IDOMENEO study).
AB  - BACKGROUND: The objective of this prospective multicenter cohort study was to
      characterise the use of pharmacological and non-pharmacological treatment for
      cardiovascular disease (CVD) risk factors and intermittent claudication (IC)
      symptoms in clinical practice patients with peripheral artery disease (PAD), and
      to determine the care gap with international guidelines and evidence-based
      therapy. PATIENTS AND METHODS: From 2011 through 2013, participating centres
      enrolled consecutive patients with PAD of atherosclerotic, origin demonstrated by
      ultrasound, ankle brachial index (ABI) < 0.9 and symptoms of IC. A seven item
      grid was built for the assessment of care gap (percentage of patients eligible
      for a treatment who did not receive it). cerebrovascular disease or at least two
      CVD risk factors. Care gap was lower than 25 % for any method to stop smoking,
      lipid lowering agents, antiplatelet and/or anticoagulation therapy and any kind
      of exercise program; between 25% and 50% for ACE inhibitors/ angiotensin II
      antagonist therapy; between 50% and 75% for beta-blocker therapy; and higher than
      75% for supervised exercise program and use of cilostazol. Patients with and
      without CADI cerebrovascular disease were differently treated with clopidogrel
      (27.3% and 4.8 %, p < 0.001), any antiplatelet/anticoagulant therapy (98.7% and
      83.3 %, p <0.001) and beta-blockers (46.8% and 16.0%, p<0.001). RESULTS: All
      patients (232) presented at least one CVC risk factor, 90.2% at least two, and
      91.5% had either established CAD or CONCLUSIONS: Many gaps with evidence-based
      recommendations are still present in the pattern of the use of pharmacological
      and non-pharmacological treatment for CVD risk factors and IC symptoms in
      clinical practice PAD patients.

PMID- 26317258
TI  - The influence of continuous local wound infusion on postoperative pain in
      patients undergoing transfemoral amputation.
AB  - BACKGROUND: This pilot study was set up to examine the effects of a continuous
      postoperative wound infusion system with a local anaesthetic on perioperative
      pain and the consumption of analgesics. PATIENTS AND METHODS: We included 42
      patients in this prospective observational pilot study. Patients were divided
      into two groups. One group was treated in accordance with the WHO standard pain
      management protocol and in addition to that received a continuous local wound
      infusion treatment (Group 1). Group 2 was treated with analgesics in accordance
      with the WHO standard pain management protocol, exclusively. RESULTS: The study
      demonstrated a significantly reduced postoperative VAS score for stump pain in
      Group 1 for the first 5 days. Furthermore, the intake of opiates was
      significantly reduced in Group 1 (day 1, Group 1: 42.1 vs. Group 2: 73.5, p =
      0.010; day 2, Group 1: 27.7 vs. Group 2: 52.5, p = 0.012; day 3, Group 1: 23.9
      vs. Group 2: 53.5, p = 0.002; day 4, Group 1: 15.7 vs. Group 2: 48.3, p = 0.003;
      day 5, Group 1 13.3 vs. Group 2: 49.9, p = 0.001). There were no significant
      differences between the two groups, neither in phantom pain intensity at
      discharge nor postoperative complications and death. CONCLUSIONS: Continuous
      postoperative wound infusion with a local anaesthetic in combination with a
      standard pain management protocol can reduce both stump pain and opiate intake in
      patients who have undergone transfemoral amputation. Phantom pain was not
      significantly affected.

PMID- 26317259
TI  - Rapid diameter expansion of aortic aneurysm after human immunodeficiency virus
      infection.

PMID- 26317260
TI  - Percutaneous thrombin embolisation of an iatrogenic pseudoaneurysm of the
      subclavian artery with neuroprotection in a critically ill patient.

PMID- 26317261
TI  - Intravascular fasciitis of the common femoral vein.

PMID- 26317262
TI  - The benefit of D-Dimer testing to decide on stopping anticoagulation after a
      first unprovoked VTE: a matter of sex or of test sensitivity?

PMID- 26317263
TI  - [Vascular Summer School 2015 - " Beta medizin interaction " in glassworks by
      05.06. - 07.06.2015].

PMID- 26317264
TI  - Comparative analysis of tools for live cell imaging of actin network
      architecture.
AB  - Fluorescent derivatives of actin and actin-binding domains are powerful tools for
      studying actin filament architecture and dynamics in live cells. Growing
      evidence, however, indicates that these probes are biased, and their cellular
      distribution does not accurately reflect that of the cytoskeleton. To understand
      the strengths and weaknesses of commonly used live-cell probes--fluorescent
      protein fusions of actin, Lifeact, F-tractin, and actin-binding domains from
      utrophin--we compared their distributions in cells derived from various model
      organisms. We focused on five actin networks: the peripheral cortex,
      lamellipodial and lamellar networks, filopodial bundles, and stress fibers. Using
      phalloidin as a standard, we identified consistent biases in the distribution of
      each probe. The localization of F-tractin is the most similar to that of
      phalloidin but induces organism-specific changes in cell morphology. Both Lifeact
      and GFP-actin concentrate in lamellipodial actin networks but are excluded from
      lamellar networks and filopodia. In contrast, the full utrophin actin-binding
      domain (Utr261) binds filaments of the lamellum but only weakly localizes to
      lamellipodia, while a shorter variant (Utr230) is restricted to the most stable
      subpopulations of actin filaments: cortical networks and stress fibers. In some
      cells, Utr230 also detects Golgi-associated filaments, previously detected by
      immunofluorescence but not visible by phalloidin staining. Consistent with its
      localization, Utr230 exhibits slow rates of fluorescence recovery after
      photobleaching (FRAP) compared to F-tractin, Utr261 and Lifeact, suggesting that
      it may be more useful for FRAP- and photo-activation-based studies of actin
      network dynamics.

PMID- 26317265
TI  - Epigenetic reprogramming in solid tumors: therapeutic implications of EZH2 gain
      of-function mutations.

PMID- 26317266
TI  - Polymer Soft-Landing Isolation of Acetylene on Polystyrene and
      Poly(vinylpyridine): A Novel Approach to Probing Hydrogen Bonding in Polymers.
AB  - Hydrogen-bonded complexes of acetylene (Ac) with the polymers polystyrene (PS),
      poly(4-vinylpyridine) (P4VP), and poly(2-vinylpyridine) (P2VP) have been
      characterized for the first time at 16 K in a "polymer soft-landing isolation"
      experiment which is being pioneered in our research laboratory. In particular,
      changes in vibrational modes of Ac provide ample evidence for hydrogen-bonded
      complexes between Ac and the phenyl groups of PS or the pyridyl groups of P4VP
      and P2VP. With PS, the proton on the top Ac molecule of the classic T-shaped Ac
      dimer interacts with the pi cloud of the benzene (Bz) ring to form a C-H---pi
      interaction, while the pi cloud of the lower Ac forms a second C-H---pi
      interaction with a proton on the Bz ring. An analogous (ring)1-(Ac)2 double
      interaction occurs between an Ac dimer and the pyridine (Pyr) rings on both P2VP
      and P4VP, yielding a C-H---N and C-H---pi interaction. With P4VP and P2VP a
      second bridged (ring)2-(Ac)2 product is formed, with the Ac dimer forming nearly
      collinear C-H---N hydrogen bonds to adjacent Pyr rings. On P2VP this bridged
      product is the only one after extensive annealing. These complexes in which Ac
      acts as both proton donor and acceptor have not previously been observed in
      conventional matrix isolation experiments. This study is the second from our
      laboratory employing this method, which represents a slight modification of the
      traditional matrix isolation technique. 

PMID- 26317267
TI  - Protein and Amino Acid Profiles of Different Whey Protein Supplements.
AB  - Whey protein (WP) supplements have received increasing attention by consumers due
      to the high nutritional value of the proteins and amino acids they provide.
      However, some WP supplements may not contain the disclosed amounts of the
      ingredients listed on the label, compromising the nutritional quality and the
      effectiveness of these supplements. The aim of this study was to evaluate and
      compare the contents of total protein (TP), alpha-lactalbumin (alpha-LA), beta
      lactoglobulin (beta-LG), free essential amino acids (free EAA), and free branched
      chain amino acids (free BCAA), amongst different WP supplements produced by U.S.
      and Brazilian companies. Twenty commercial brands of WP supplements were
      selected, ten manufactured in U.S. (WP-USA) and ten in Brazil (WP-BRA). The TP
      was analyzed using the Kjeldahl method, while alpha-LA, beta-LG, free EAA, and
      free BCAA were analyzed using HPLC system. There were higher (p < 0.05)
      concentrations of TP, alpha-LA, beta-LG, and free BCAA in WP-USA supplements, as
      compared to the WP-BRA supplements; however, there was no difference (p > 0.05)
      in the content of free EAA between WP-USA and WP-BRA. Amongst the 20 brands
      evaluated, four WP-USA and seven WP-BRA had lower (p < 0.05) values of TP than
      those specified on the label. In conclusion, the WP-USA supplements exhibited
      better nutritional quality, evaluated by TP, alpha-LA, beta-LG, and free BCAA
      when compared to WP-BRA. 

PMID- 26317268
TI  - Individual differences in the cortisol-awakening response during the first two
      years of shift work: A longitudinal study in novice police officers.
AB  - Cortisol acts as a critical biological intermediary through which chronic
      stressors like shift work impact upon multiple physiological, neuro-endocrine and
      hormonal functions. Therefore, the cortisol awakening response (CAR) is suggested
      as a prime index of shift work tolerance. Repeated assessments of the CAR
      (calculated as MnInc) in a group of 25 young novice police officers showed that
      in the interval between about 4 and 14 months after transitioning from regular
      day work to rotating shift work, mean values began to rise from baseline to
      significantly higher levels at about 14 months after they commenced shift work.
      Visual inspection of the individual trends revealed that a subgroup of 10
      subjects followed a monotonically rising trend, whereas another 14 subjects,
      after an initial rise from about 4-14 months, reverted to a smaller, baseline
      level cortisol response at about 20 months after the start of shift work. If the
      initial increase in the cortisol response marks the development of a chronic
      stress response, the subsequent reversal to baseline levels in the subgroup of 14
      participants might be indicative of a process of recovery, possibly the
      development of shift work tolerance. 

PMID- 26317269
TI  - Retail Tobacco Sale in the Community. Should Pharmacies Sell Tobacco Products?

PMID- 26317270
TI  - Viewing Lung Cancer in Color Instead of Black and White.

PMID- 26317271
TI  - Emphysema and Lung Cancer. More Than a Coincidence.

PMID- 26317272
TI  - The Whole Picture. A 23-Year-Old Diabetic Female with Persistent Pneumonia and
      Chronic Lung Abscess.

PMID- 26317273
TI  - A Young Man with a Mediastinal Mass and Sudden Cardiac Arrest.

PMID- 26317274
TI  - Calcified Lymph Node. An Unusual Cause of Hemoptysis.

PMID- 26317275
TI  - An Unanticipated Pattern of Sleep-Disordered Breathing in a Patient with Multiple
      Sclerosis.

PMID- 26317276
TI  - Regional Sparing in an Oligemic Lung Segment Supports Hematogenous Spread as a
      Pathogenic Mechanism in Lymphangioleiomyomatosis.

PMID- 26317277
TI  - Azathioprine for the Rare Case of Nonspecific Interstitial Pneumonitis in a
      Patient with Psoriasis.

PMID- 26317278
TI  - Possible Involvement of Lung Cells Harboring an Abnormal Karyotype in the
      Pathogenesis of Pulmonary Alveolar Proteinosis Associated with Myelodysplastic
      Syndrome.

PMID- 26317279
TI  - Endobronchial Ultrasound Transbronchial Needle Injection: Ex Vivo Measurement of
      Dead Space Volume of the Needle Assembly.

PMID- 26317280
TI  - Reply: Endobronchial Ultrasound Transbronchial Needle Injection: Ex Vivo
      Measurement of Dead Space Volume of the Needle Assembly.

PMID- 26317283
TI  - The Aux/IAA, Sl-IAA17 regulates quality parameters over tomato fruit development.
AB  - Auxin is known to be involved in all the stages of fruit development. Aux/IAAs
      are regulators of the auxin signaling at the transcription level. In a recent
      study, using RNAi strategy to limit the expression Sl-IAA17, it was shown that
      this tomato AuxIAA regulates fruit size mainly through altering the ploidy level
      of pericarp cells. Indeed, Sl-IAA17 down-regulated lines showed fruit with larger
      diameter, bigger volume and heavier weight than wild-type. The increase in fruit
      size was associated with thicker pericarp rather than larger locular spaces. The
      thicker pericarp was linked to larger cells harboring higher ploidy level,
      probably due to more active endoreduplication at the beginning of fruit
      development. The present report describes some additional phenotypes, not
      described in the initial article, among which are soluble solid content, juice
      pH, firmness, seed weight and fruit morphology.

PMID- 26317284
TI  - Total population-based study of the impact of substance use disorders on the
      overall survival of psychiatric inpatients.
AB  - BACKGROUND: Patients with severe mental illness have a shortened lifespan, and
      substance use disorder (SUD) is an especially important diagnosis in this
      respect. There have been no studies comparing directly SUD to other diagnoses in
      a nationwide cohort. AIMS: To directly compare differences in mortality rates of
      psychiatric inpatients with a discharge diagnosis of SUD versus other psychiatric
      diagnoses. METHODS: A register-based study was made of all patients admitted to
      psychiatric hospitals in Iceland between 1983 and 2007. Patients were grouped
      according to discharge diagnoses. Survival with respect to SUD was compared using
      Cox-proportional hazard ratio, excluding those with an organic mental disorder.
      Furthermore, the survival of patients with SUD and co-morbid diagnoses was
      evaluated. RESULTS: A total of 14,281 patients (over the age of 18 years) were
      admitted to a psychiatric hospital in Iceland during the study period, with a
      total of 156,356 years of follow-up. For both men and women, a diagnosis of SUD
      conferred similar mortality as a diagnosis of schizophrenia without SUD, while
      individuals with a diagnosis of a mood disorder or "other disorders" had
      significantly lower mortality than SUD. For men with SUD, a co-occurring mental
      disorder was associated with an increased risk of dying, however, this was not
      found for women. CONCLUSIONS: SUD was the psychiatric diagnosis that had the
      highest mortality rate among psychiatric inpatients, in both men and women. An
      additional psychiatric diagnosis on a pre-existing SUD diagnosis did increase the
      risk for men but not women.

PMID- 26317285
TI  - Biochemical Validation of Self-Reported Smokeless Tobacco Abstinence among
      Smokeless Tobacco Users: Results from a Clinical Trial of Varenicline in India.
AB  - The validity of self-reported tobacco use is often questioned given the potential
      for underestimation of use. This study used data from a double-blind, placebo
      controlled clinical trial of varenicline for smokeless tobacco dependence in
      India to evaluate the accuracy of self-reported smokeless tobacco cessation using
      biochemical validation procedures and to evaluate correlates of reporting
      inaccuracy. Smokeless tobacco users attending a dental clinic at AIIMS were
      randomized to placebo or varenicline; all participants received counseling.
      Detailed smokeless tobacco use was recorded and abstinence was defined as
      cotinine-verified 7-day point prevalence cessation (cotinine < 50 ng/ml) and
      breath CO > 10 ppm at the end of 12 weeks of treatment. One-half of study
      completers (82/165) self-reported abstinence. Biochemical verification confirmed
      that (65.9%) subjects provided accurate self-reports while (34.1%) participants
      underreported tobacco use. These data indicate poor agreement between self
      reported and biochemically confirmed abstinence (kappa = -0.191). Underreporters
      of tobacco use had significantly higher baseline cotinine (p < 0.05), total
      craving (p < 0.012), and negative reinforcement craving (p < 0.001) vs. those
      whose self-reports were correctly verified. These findings provide evidence to
      support the need for biochemical validation of self-reported abstinence outcomes
      among smokeless tobacco users in cessation programs in India and identify high
      levels of pretreatment cotinine and craving levels as potential correlates of
      false reporting. 

PMID- 26317286
TI  - Polyamine-Mediated Interfacial Assembly of rGO-ZnO Nanostructures: A Bio-inspired
      Approach and Enhanced Photocatalytic Properties.
AB  - A bio-inspired approach for the fabrication of reduced graphene oxide (rGO)
      embedded ZnO nanostructure has been attempted to address issues pertaining to
      charge recombination and photocorrosion in ZnO for application as an effective
      photocatalyst. Herein we demonstrate the synthesis of rGO-ZnO nanostructures in a
      single step using polyamines, which simultaneously aid in the mineralization of
      ZnO nanostructures from zinc nitrate, reduction of graphene oxide (GO), and
      finally their assembly to form rGO-ZnO composite structures under environmentally
      benign conditions. The interspersed nanocomponents in the assembled
      heterostructures result in enhanced photocatalytic activity under UV light,
      indicating an effective charge separation of the excited electrons. Furthermore,
      the composite structure provides stability against photocorrosion for efficient
      recyclability of the catalyst. 

PMID- 26317287
TI  - Radial head prosthesis after radial head and neck fractures - current literature
      and quality of evidence.
AB  - Due to the elbow joint's complex functional anatomy, the multifragmentary nature
      of many fractures and concomitant destabilizing associated injuries, dislocated
      fractures of the radial head and neck still present a serious challenge for the
      orthopedic surgeon. Thorough knowledge of the elbow's anatomy and biomechanics is
      essential to analyze and understand the injury and plan its treatment. The aim of
      a differentiated therapy approach is to restore the joint's anatomy and kinetics,
      stable and painless joint function, and to avoid or at least delay posttraumatic
      joint changes. The degree of dislocation, stability of fragments, size and number
      of fractured joint surfaces and associated bony and ligamentous injuries (and the
      instability they incur) must be addressed in the therapy regimen. There are
      various treatment options depending on the injury's classification, i.e. a Mason
      I fracture is treated conservatively, while more severe injuries may require
      osteosynthesis and endoprosthesis. There is a lack of clear therapy
      recommendations based on solid evidence regarding Mason classification types III
      IV. In particular expert opinions diverge and study results are inconsistent.
      Especially the value of radial head arthroplasty is still hotly debated. Key
      words: radial head fracture, radial head prosthesis, radial neck fracture, Mason
      classification, radial head arthroplasty, elbow injury. 

PMID- 26317288
TI  - [Continuous passive motion in joint rehabilitation after injury and surgery].
AB  - Devices for continuous passive motion, also known as motor-driven splints, are
      widely used in rehabilitation therapy following injuries and surgery. They
      present an adjunct method substituting the physical work of a physiotherapist.
      The method is indicated in early post-injury or post-operative periods. It is
      expected to increase blood drainage and remove haemarthrosis and synovial fluid
      exudate which precede an undesired development of granulation and fibrous
      tissues. However, continuing such an intensive therapy after 3 to 4 post
      operative weeks lacks its raison d'etre. The only exceptions include conditions
      after autologous chondrocyte transplantation and a supplementary therapy to
      active rehabilitation programmes for releasing muscle hypertonia which restricts
      movement. Values for the range of motion set up on the device cannot be
      considered the real values pertinent to the exercised joint; these are usually
      considerably lower. Key words: continuous passive motion, motor-driven splint. 

PMID- 26317289
TI  - Skeletal metastatic disease of the femur: results by management with
      intramedullary nailing.
AB  - PURPOSE OF THE STUDY This study aimed to analyse the outcome following
      intramedullary nailing for metastases of the femur in a large cohort with special
      regard to mechanical, implant associated complications and patient survival.
      Furthermore, we aimed to identify factors influencing the overall survival.
      MATERIAL AND METHODS All patients (n = 74) that underwent intramedullary nailing
      for metastatic disease of the femur between 2004 and 2008 and were
      retrospectively reviewed. Data were recorded from the patients' medical record
      and the outpatients' clinics files. Details about the tumour biology, the surgery
      performed as well as the postoperative care were documented. Survival data were
      extracted from patient records or obtained via communication with outpatient
      oncologists or the community registration office. RESULTS 74 (28 (37.8%) male, 46
      (62.2%) female; p = 0.048) patients with a mean age of 64.4 +/- 11.7 years were
      included. Breast (25, 33.8%), lung (18, 24.3%), bone marrow (7, 9.5%) and kidney
      (6, 8.1%) were the primary tumours in more than 75% of all patients. The mean
      overall survival was 17.5 (95% CI: 9.6 - 25.5) months. Patients with osseous
      metastases had a significant longer survival than patients with visceral and/or
      cerebral metastases (p = 0.025 and p = 0.032). CONCLUSION Intramedullary nailing
      represents a valuable fixation method for pathologic fractures or impending
      fractures of the femur in patients with an advanced stage of metastatic disease.
      It provides adequate stability to outlast the patient s remaining life-span.
      However, the balance must be found between therapeutic resignation and surgical
      overtreatment since operative treatment may be accompanied with serious
      complications. Key words: bone metastases, intramedullary nailing, metastatic
      disease, cement augmentation, osteolytic defect. 

PMID- 26317290
TI  - Measurement of compartment elasticity using pressure related ultrasound: a method
      to identify patients with potential compartment syndrome.
AB  - PURPOSE OF THE STUDY Decision-making in treatment of an acute compartment
      syndrome is based on clinical assessment, supported by invasive monitoring. Thus,
      evolving compartment syndrome may require repeated pressure measurements. In
      suspected cases of potential compartment syndromes clinical assessment alone
      seems to be unreliable. The objective of this study was to investigate the
      feasibility of a non-invasive application estimating whole compartmental
      elasticity by ultrasound, which may improve accuracy of diagnostics. MATERIAL AND
      METHODS In an in-vitro model, using an artificial container simulating dimensions
      of the human anterior tibial compartment, intracompartmental pressures (p) were
      raised subsequently up to 80 mm Hg by infusion of saline solution. The
      compartmental depth (mm) in the cross-section view was measured before and after
      manual probe compression (100 mm Hg) upon the surface resulting in a linear
      compartmental displacement (Deltad). This was repeated at rising compartmental
      pressures. The resulting displacements were related to the corresponding intra
      compartmental pressures simulated in our model. A hypothesized relationship
      between pressures related compartmental displacement and the elasticity at
      elevated compartment pressures was investigated. RESULTS With rising
      compartmental pressures, a non-linear, reciprocal proportional relation between
      the displacement (mm) and the intra-compartmental pressure (mm Hg) occurred. The
      Pearson's coefficient showed a high correlation (r2 = -0.960). The intraobserver
      reliability value kappa resulted in a statistically high reliability (kappa =
      0.840). The inter-observer value indicated a fair reliability (kappa = 0.640).
      CONCLUSIONS Our model reveals that a strong correlation between compartmental
      strain displacements assessed by ultrasound and the intra-compartmental pressure
      changes occurs. Further studies are required to prove whether this assessment is
      transferable to human muscle tissue. Determining the complete compartmental
      elasticity by ultrasound enhancement, this application may improve detection of
      early signs of potential compartment syndrome. Key words: compartment syndrome,
      intra-compartmental pressure, non-invasive diagnostic, elasticity measurement,
      elastography. 

PMID- 26317291
TI  - Retrograde tibial nail: anatomical implantation and surgical feasibility study.
AB  - PURPOSE OF THE STUDY The treatment of distal tibial fractures requires a stable
      fixation while minimizing the secondary trauma to the soft tissues by the
      surgical approach and implant. The experimental Retrograde Tibial Nail is
      currently investigated as a minimally invasive alternative to plating and
      antegrade nailing. The purpose of this study was to evaluate the surgical
      feasibility in a cadaver model for all distal tibial fracture types generally
      considered treatable by nailing. MATERIAL AND METHODS Five different fracture
      types (AO/OTA 43-A1/A2/A3 and 43-C1/C2) were created on separate cadaveric limbs.
      In simple fractures (AO/OTA 43-A1/A2/A3) primary nailing was performed. In
      intraarticular fractures (AO/OTA 43-C1/2) reduction of the articular block and
      lag screw fixation was performed before nailing. Intraoperative complications,
      quality of reduction, fluoroscopy duration and operative time were evaluated.
      RESULTS Retrograde intramedullary nailing is feasible in simple fracture types by
      closed manual reduction and percutaneous reduction forceps. Retrograde nailing is
      possible in fractures with simple intraarticular involvement after primary lag
      screw fixation. The duration of surgery averaged 51.8 minutes (range 40-62 min).
      No major complications occurred during nailing. CONCLUSIONS The minimally
      invasive retrograde nail combines a minimally invasive local osteosynthesis with
      the ability to adequately fix extraarticular and simple intraarticular distal
      tibial fractures. The results suggests that retrograde tibia nailing is a
      promising new concept for the treatment of distal tibia fractures. Key words:
      minimally invasive surgery, tibia, metaphyseal fractures, intramedullary nailing,
      retrograde nailing. 

PMID- 26317292
TI  - [Long-term results of surgery for cervical spondylotic myelopathy using open-door
      laminoplasty].
AB  - PURPOSE OF THE STUDY Cervical spondylotic myelopathy (CSM) is a serious disease
      which, in its advanced form, can markedly disable the patient. The aim of the
      present work was a prospective evaluation of a group of CSM patients treated by
      open-door laminoplasty. MATERIAL AND METHODS We evaluated 89 patients (59 men and
      30 women; average age, 62 years; range, 39 to 81 years) who underwent surgery in
      the years 2001 to 2011. The average follow-up was 76 months. The patients were
      examined neurologically, radiologically, by magnetic resonance imaging (MRI) or
      CT. All of them had quadruparetic disability and showed signs of myelopathy on
      MRI examination. We used a modified Hirabayashi technique of open-door
      laminoplasty. We evaluated the surgery time, intra-operative blood loss,
      neurological deficit on the modified Japanese Orthopaedic Society (mJOA) scale,
      intra- and postoperative complications, neck pain (NP) and extremity pain (EP) on
      the visual analogue scale (VAS) and a radiographic sagittal profile change after
      laminoplasty. RESULTS The average operative time was 117 minutes and the average
      intra-operative blood loss was 330 ml. The average mJOA score of 12.7 before
      surgery improved to 14.4. Two patients (2.25 %) showed persisting deterioration
      of neurological symptoms, conditions of six patients (6.75 %) were assessed as
      stable and the remaining 81 patients (91 %) showed varying degrees of both
      subjective and objective amelioration/improvement. Infection was recorded as the
      most frequent complication (7.8 %). C5 paresis reported in the literature did not
      occur in our group. One patient (1.1 %) had a moderate epidural haemorrhage. The
      pre-operative VAS NP score of 5.4 improved to 3.2 and the VAS EP score of 7.7
      improved to 4.4. The average value for the radiographic sagittal profile changed
      from -18.2 pre-operatively to -16.5 post-operatively. CONCLUSIONS Laminoplasty
      remains the basic surgical option for CSM treatment, particularly in progressive
      cases of the disease, in multi-segmental disease, and in need to preserve or
      restore cervical spine alignment Key words: cervical spondylotic myelopathy,
      laminoplasty, Hirabayashi open-door technique, mJOA score, complications, VAS. 

PMID- 26317293
TI  - [Kirschner wire transfixation of unstable ankle fractures: indication, surgical
      technique and outcomes].
AB  - PURPOSE OF THE STUDY The aim of the study was to assess treatment outcomes in
      patients undergoing K-wire transfixation of unstable ankle fractures and compare
      the results with those of patients in whom it was possible to perform primary one
      stage osteosynthesis. MATERIAL AND METHODS Between 2009 and 2012, a total of 358
      patients (191 women and 167 men) had surgery for unstable ankle fracture. At 1
      year follow-up, their subjective feelings, objective findings and ankle
      radiographs were evaluated. The fractures were categorised according to the Weber
      classification. A patient group treated by one-stage osteosynthesis, a group with
      definitive transfixation and a group of patients in whom temporary transfixation
      was converted to definitive osteosynthesis were assessed and compared. RESULTS
      The group treated by one-stage osteosynthesis included 278 patients with an
      average age of 47 years; the group of 20 patients with definitive transfixation
      had an average age of 67 years, and the group of 60 patients who had temporary
      transfixation with subsequent conversion to internal osteosynthesis were 55 years
      on average. In the group with one-stage osteosynthesis, 223 (80%) ankle fractures
      on post-injury radiographs were associated with minor joint dislocations and 55
      (20%) with major dislocations. On the other hand, the radiographs of the patients
      treated by temporary transfixation and delayed open reduction with internal
      fixation showed major dislocations in 38 (63%) and minor dislocations in the rest
      of the patients (37%); the difference between the two groups was statistically
      significant (p<0.001). Posterior malleolar fractures were most frequent in the
      group with temporary transfixation (60%) and least frequent in the group with
      primary osteosynthesis (44%); also this difference was statistically significant
      (p=0.032). At one-year follow-up, in the group with one-stage osteosynthesis, 220
      patients (79%) had no radiographic signs of posttraumatic ankle osteoarthritis
      while, in the group with temporary transfixation, no radiographic evidence of
      ankle osteoarthritis was recorded in 25 (42%) patients. While tibiofibular
      synostosis was recorded in only few patients (9%) of the group with one-stage
      osteosynthesis, it showed a high occurrence in the group with temporary
      transfixation (35%). The patients with one-stage osteosynthesis (188/68%) had a
      higher proportion of excellent outcomes measured on the Olerund-Molander ankle
      scoring scale than the other two groups (temporary transfixation, 47%; definitive
      transfixation,10%); in both cases the difference was significant (p < 0.001 and p
      = 0.003, respectively). DISCUSSION In this study the morphological and clinical
      aspects of surgically treated ankle fractures were assessed. The patients with
      one-stage osteosynthesis were compared with those treated by temporary or
      definitive transfixation. The majority of patients undergoing temporary
      transfixation had a fractured posterior margin of the tibia and major ankle joint
      dislocation, which suggested serious injuries to bone and ligament structures.
      Generally, the use of only two K-wires inserted through the calcaneus and talus
      into the distal tibia is recommended. Patients with K-wire transfixation usually
      require a longer hospital stay because of the serious nature of their injuries.
      CONCLUSIONS The therapy of choice for unstable ankle fractures is one-stage
      osteosynthesis. Temporary transfixation is an effective method of primary
      management when an unstable fracture cannot be treated by definitive
      osteosynthesis at the early stage due to local or general health conditions of
      the patient. The temporary transfixation provides good alignment of the ankle
      joint necessary for successful healing of soft tissues. A higher occurrence of
      post-traumatic ankle osteoarthritis, ossification and distal tibiotalar
      synostosis found in the patients treated by temporary transfixation is more
      related to serious types of ankle fractures the patient had suffered than to the
      method itself. Key words: unstable ankle fracture, soft tissue condition,
      indications for transfixation, treatment outcome. 

PMID- 26317294
TI  - [Intra-articular reinforcement of a partially torn anterior cruciate ligament
      (ACL) using newly developed UHMWPE biomaterial in combination with Hexalon
      ACL/PCL screws: ex-vivo mechanical testing of an animal knee model].
AB  - PURPOSE OF THE STUDY Recent trends in the experimental surgical management of a
      partial anterior cruciate ligament (ACL) rupture in animals show repair of an ACL
      lesion using novel biomaterials both for biomechanical reinforcement of a
      partially unstable knee and as suitable scaffolds for bone marrow stem cell
      therapy in a partial ACL tear. The study deals with mechanical testing of the
      newly developed ultra-high-molecular-weight polyethylene (UHMWPE) biomaterial
      anchored to bone with Hexalon biodegradable ACL/PCL screws, as a new possibility
      of intra-articular reinforcement of a partial ACL tear. MATERIAL AND METHODS Two
      groups of ex vivo pig knee models were prepared and tested as follows: the model
      of an ACL tear stabilised with UHMWPE biomaterial using a Hexalon ACL/PCL screw
      (group 1; n = 10) and the model of an ACL tear stabilised with the traditional,
      and in veterinary medicine used, extracapsular technique involving a monofilament
      nylon fibre, a clamp and a Securos bone anchor (group 2; n = 11). The models were
      loaded at a standing angle of 100 degrees  and the maximum load (N) and shift
      (mm) values were recorded. RESULTS In group 1 the average maximal peak force was
      167.6 +/- 21.7 N and the shift was on average 19.0 +/- 4.0 mm. In all 10
      specimens, the maximum load made the UHMWPE implant break close to its fixation
      to the femur but the construct/fixation never failed at the site where the
      material was anchored to the bone. In group 2, the average maximal peak force was
      207.3 +/- 49.2 N and the shift was on average 24.1 +/- 9.5 mm. The Securos
      stabilisation failed by pullout of the anchor from the femoral bone in nine out
      of 11 cases; the monofilament fibre ruptured in two cases. CONCLUSIONS It can be
      concluded that a UHMWPE substitute used in ex-vivo pig knee models has mechanical
      properties comparable with clinically used extracapsular Securos stabilisation
      and, because of its potential to carry stem cells and bioactive substances, it
      can meet the requirements for an implant appropriate to the unique technique of
      protecting a partial ACL tear. In addition, it has no critical point of ACL
      substitute failure at the site of its anchoring to the bone (compared to the
      previously used PET/PCL substitute). Key words: knee stabilisation, stifle
      surgery, ultra-high-molecular-weight polyethylene, UHMWPE, nylon monofilament
      thread, biodegradable screw, bone anchor. 

PMID- 26317295
TI  - [Use of cultured human autologous bone marrow stem cells in repair of a rotator
      cuff tear: preliminary results of a safety study].
AB  - PURPOSE OF THE STUDY Rotator cuff tears are one of the most frequent shoulder
      disorders which are often associated with pain and interfere with proper arm
      function. In order to evaluate the safety and effectiveness of using cultured
      human autologous mesenchymal stem cells (MSC) applied to the suture site during
      arthroscopic repair of a rotator cuff tear, a prospective clinical study was
      designed and started recently at the authors' department. Its primary goal was to
      evaluate the safety of using cultured human MSCs, the secondary goal then was to
      study a therapeutic effect of their application. Preliminary results of the study
      on a limited number of patients are presented here. MATERIAL AND METHODS Ten
      patients who met the indication criteria for arthroscopic repair of a rotator
      cuff tear were included in the study. In addition, they also had to meet
      inclusion and lack exclusion criteria. According to the protocol, their bone
      marrow was harvested at 3 to 4 weeks before surgery. Subsequently, an
      arthroscopic repair of the rotator cuff tear was performed and an suspension of
      cultured MSCs was applied to the suture site at the end of the procedure. The
      isolation of MSCs from bone marrow and their cultivation was carried out by the
      company Bioinova, Ltd. The patients were followed up at 6 weeks and 3 and 6
      months post-operatively. Their clinical assessment included physical examination
      of the shoulder, pain intensity evaluation according to the visual analogue scale
      (VAS), and subjective questionnaires for Constant and University of California
      (UCLA) scores. All patients underwent MRI examination at 6 post-operative months
      to evaluate the quality of rotator cuff reconstruction. The findings were
      compared with the pre-operative results. RESULTS A final evaluation was made in
      eight patients of 10. Two patients were excluded from the study because their
      exclusion criteria were fulfilled. The evaluated patients showed significantly
      better clinical outcomes as early as 6 weeks after surgery; also all pre
      operative scores were improved at 3 and 6 months. The average values at 6 months
      post-operatively were: 0 points for the VAS score, 32 for the UCLA score and 84
      for the Constant score. The MRI findings at 6 months after surgery showed fully
      healed and well-integrated tissue of the rotator cuff tendon attachment in all
      eight patients. No adverse effects of therapy were recorded during the follow-up
      period. DISCUSSION The use of autologous stem cells and growth factors in the
      treatment of tendons, muscles and cartilage is currently the topic of many
      experimental studies on animal models. Its utilisation in human clinical trials
      has been reported only marginally; the relevant studies have so far used only
      suspensions of non-cultured mononuclear cells. Our study, although on a smallsize
      patient group, provides evidence that human cultured autologous MSCs can safely
      be used for tissue repair in the indications mentioned above. CONCLUSIONS Our
      preliminary short-term results show that using human cultured autologous MSCs in
      the treatment of rotator cuff tears is safe. However, further research is needed,
      particularly with regard to the effectiveness of the method. Key words: rotator
      cuff tear, arthroscopic repair, mesenchymal stem cells, tendon, cell therapy. 

PMID- 26317296
TI  - [Odontoid bending stiffness after anterior fixation with a single lag screw:
      biomechanical study].
AB  - PURPOSE OF THE STUDY The aim of the experiment was to compare the bending
      stiffness of an intact odontoid process with bending stiffness after its
      simulated type II fracture was fixed with a single lag screw. The experiment was
      done with a desire to answer the question of whether a single osteosynthetic
      screw is sufficient for good fixation of a type II odontoid fracture. MATERIAL
      AND METHODS The C2 vertebrae of six cadavers were used. With simultaneous
      measurement of odontoid bending stiffness, the occurrence of a fracture (type
      IIA, Grauer's modification of the Anderson- D'Alonzo classification) was
      simulated using action exerted by a tearing machine in the direction
      perpendicular to the odontoid axis. Each odontoid fracture was subsequently
      treated by direct osteosynthesis with a single lag screw inserted in the axial
      direction by a standard surgical procedure in order to provide conditions similar
      to those achieved by routine surgical management. The treated odontoid process
      was subsequently subjected to the same tearing machine loading as applied to it
      at the start of the experiment. The bending stiffness measured was then compared
      with that found before the fracture occurred. The results were statistically
      evaluated by the t-test for paired samples at the level of significance alpha =
      0.05. RESULTS The average value of bending stiffness for odontoid processes of
      intact vertebrae at the moment of fracture occurrence was 318.3 N/mm. After
      single axial lag screw fixation of the fracture, the average bending stiffness
      for the odontoid processes treated was 331.3 N/mm. DISCUSSION Higher values of
      bending stiffness after screw fixation were found in all specimens and, in
      comparison with the values recorded before simulated fractures, the increase was
      statistically significant. CONCLUSIONS The results of our measurements suggest
      that the single lag screw fixation of a type IIA odontoid fracture will provide
      better stability for the fracture fragment-C2 body complex on antero-posterior
      perpendicular loading than can be found in intact C2 vertebrae. Key words:
      odontoid fracture, odontoid fixation, bending stiffness, lag screw. 

PMID- 26317297
TI  - Salvage total hip arthroplasty after two gamma 3 nail failures: a case report.
AB  - We report a case of 68-year-old female patient who suffered two Gamma 3 nail
      breakages following trochanteric fixation failure revision surgery. A patient was
      primarily treated with sliding hip screw. Revision surgeries of reverse
      trochanteric nonunion were performed with short Gamma 3 nails and bone grafting.
      The nail failures occurred 11 and 7 months after implantation. This undesired
      series of events were caused by inappropriate implant selection, thus replacing
      the nail to a modular total hip arthroplasty was more effective as salvage
      surgery. Key words: salvage total hip arthroplasty, gamma nail, sliding hip
      screw, fixation failure, reverse trochanteric fracture, nonunion. 

PMID- 26317298
TI  - The Effect of Residual Acoustic Hearing and Adaptation to Uncertainty on Speech
      Perception in Cochlear Implant Users: Evidence From Eye-Tracking.
AB  - OBJECTIVES: While outcomes with cochlear implants (CIs) are generally good,
      performance can be fragile. The authors examined two factors that are crucial for
      good CI performance. First, while there is a clear benefit for adding residual
      acoustic hearing to CI stimulation (typically in low frequencies), it is unclear
      whether this contributes directly to phonetic categorization. Thus, the authors
      examined perception of voicing (which uses low-frequency acoustic cues) and
      fricative place of articulation (s/?, which does not) in CI users with and
      without residual acoustic hearing. Second, in speech categorization experiments,
      CI users typically show shallower identification functions. These are typically
      interpreted as deriving from noisy encoding of the signal. However,
      psycholinguistic work suggests shallow slopes may also be a useful way to adapt
      to uncertainty. The authors thus employed an eye-tracking paradigm to examine
      this in CI users. DESIGN: Participants were 30 CI users (with a variety of
      configurations) and 22 age-matched normal hearing (NH) controls. Participants
      heard tokens from six b/p and six s/? continua (eight steps) spanning real words
      (e.g., beach/peach, sip/ship). Participants selected the picture corresponding to
      the word they heard from a screen containing four items (a b-, p-, s- and ?
      initial item). Eye movements to each object were monitored as a measure of how
      strongly they were considering each interpretation in the moments leading up to
      their final percept. RESULTS: Mouse-click results (analogous to phoneme
      identification) for voicing showed a shallower slope for CI users than NH
      listeners, but no differences between CI users with and without residual acoustic
      hearing. For fricatives, CI users also showed a shallower slope, but
      unexpectedly, acoustic + electric listeners showed an even shallower slope. Eye
      movements showed a gradient response to fine-grained acoustic differences for all
      listeners. Even considering only trials in which a participant clicked "b" (for
      example), and accounting for variation in the category boundary, participants
      made more looks to the competitor ("p") as the voice onset time neared the
      boundary. CI users showed a similar pattern, but looked to the competitor more
      than NH listeners, and this was not different at different continuum steps.
      CONCLUSION: Residual acoustic hearing did not improve voicing categorization
      suggesting it may not help identify these phonetic cues. The fact that acoustic +
      electric users showed poorer performance on fricatives was unexpected as they
      usually show a benefit in standardized perception measures, and as sibilants
      contain little energy in the low-frequency (acoustic) range. The authors
      hypothesize that these listeners may overweight acoustic input, and have problems
      when this is not available (in fricatives). Thus, the benefit (or cost) of
      acoustic hearing for phonetic categorization may be complex. Eye movements
      suggest that in both CI and NH listeners, phoneme categorization is not a process
      of mapping continuous cues to discrete categories. Rather listeners preserve
      gradiency as a way to deal with uncertainty. CI listeners appear to adapt to
      their implant (in part) by amplifying competitor activation to preserve their
      flexibility in the face of potential misperceptions.

PMID- 26317299
TI  - Insulin signaling genes modulate nicotine-induced behavioral responses in
      Caenorhabditis elegans.
AB  - Insulin signaling has been suggested to modulate nicotine dependence, but the
      underlying genetic evidence has been lacking. Here, we used the nematode,
      Caenorhabditis elegans, to investigate whether genetic alterations in the insulin
      signaling pathway affect behavioral responses to nicotine. For this, we
      challenged drug-naive C. elegans with an acute dose of nicotine (100 MUmol/l)
      while recording changes in their locomotion speed. Although nicotine treatment
      stimulated locomotion speed in wild-type C. elegans, the same treatment reduced
      locomotion speed in mutants defective in insulin signaling. This phenotype could
      be suppressed by mutations in daf-16, a gene encoding a FOXO transcription factor
      that acts downstream of insulin signaling. Our data suggest that insulin
      signaling genes, daf-2, age-1, pdk-1, akt-1, and akt-2, modulate behavioral
      responses to nicotine in C. elegans, indicating a genetic link between nicotine
      behavior and insulin signaling. 

PMID- 26317300
TI  - Effects of Workloads and Cadences on Frontal Plane Knee Biomechanics in Cycling.
AB  - Although effects of workload and cadence on sagittal plane knee biomechanics in
      cycling have been widely studied, few studies have examined their impact on the
      frontal plane. PURPOSE: The purpose of this study was to investigate the effects
      of different workloads and cadences on knee sagittal and frontal plane
      biomechanics. METHODS: Eighteen healthy participants (age, 55.7 +/- 11.0 yr)
      volunteered for this study. A motion analysis system and a custom instrumented
      pedal were used to collect five cycles of three-dimensional kinematics (240 Hz)
      and pedal reaction force (PRF, 1200 Hz) during 2 min of cycling in each of eight
      testing conditions, including five workload conditions of 0.5, 1, 1.5, 2, and 2.5
      kg at 60 rpm, and three cadence conditions of 70, 80, and 90 rpm with 1-kg
      workload. Two one-way repeated measures analyses of variance were used to examine
      the influence of cadence and workload on selected variables (P < 0.05). RESULTS:
      Increased workloads with constant rpm caused an increased peak knee abduction
      moment from 5.82 to 14.36 N . m and peak knee extension moment from 11.61 to
      37.16 N . m. Increased workloads also significantly increased peak medial and
      vertical PRF. Increased cadences at the constant workload had no effects on peak
      knee abduction moment but caused increased peak anterior and vertical PRF and
      peak knee flexion moment. CONCLUSIONS: The findings of this study indicate that
      increasing workload at constant cadence significantly increased peak knee
      abduction moment. Further study may be needed to demonstrate the efficacy of
      appropriate levels of workload and cadence in knee osteoarthritis and other
      populations with knee problems.

PMID- 26317301
TI  - Are there differences in health information exchange by health system type?
AB  - BACKGROUND: Despite the potential of health information exchange (HIE) to improve
      safety and reduce cost, hospitals have been slow to adopt HIE with only 30% of
      U.S. hospitals doing so in 2012. PURPOSE: The aim of this study was to explore
      the relationship between different health system types and how they engage in
      HIE. METHODS: Data on health system types and engagement in HIE activity were
      combined with secondary hospital characteristics. Ordinal logistic regression
      analyses were used to examine the relationship between a scale measuring the
      level of HIE engagement and health system type controlling for hospital and
      market characteristics. RESULTS: Data from 1552 hospitals were available for
      analyses. Overall, hospital in a health system of any kind exchanged more patient
      data elements (e.g., patient demographics, clinical summaries, laboratory
      results, medication history, and radiology report) compared with stand-alone
      hospitals (3.82 vs. 1.80, p < .001). Overall, 62.2% of hospitals were part of a
      health system, and among system hospitals, 125 (8.0%) were in centralized health
      systems, 75 (4.8%) were in centralized physician/insurance health system, 284
      (18.3%) were in moderately centralized health system, 391 (25.2%) were in
      decentralized health system, and 91 (5.9%) were in independent health system. In
      regression analyses, hospitals belonging to a health system were more likely to
      exchange patient health data with other hospitals in the same system (OR = 3.94,
      p < .001) but not with hospitals outside their system (OR = 1.89, p = .445).
      Across health system types, there was no significant difference in the exchange
      of patient health data. PRACTICE IMPLICATIONS: Hospital engagement in HIE is
      associated with health system membership. These findings will assist hospital
      leaders and managers to better understand how the structure and nature of their
      system may influence what their individual hospital can and cannot do in their
      decision to engage in HIE and other decisions that support the overall system
      objectives.

PMID- 26317302
TI  - The unique effects of general and specific support in health care technology: An
      empirical examination of the principle of compatibility.
AB  - BACKGROUND: The principle of compatibility suggests that specific attitudes
      should target specific behaviors. The attitude-behavior relationship is
      contingent upon the consistency between the two. PURPOSE: This aim of this study
      was to examine the strength of relationships involving general versus specific
      support perceptions and attitudes regarding smart pump technology in hospitals.
      Specifically, we hypothesized that organizational support perceptions would be
      more strongly related to general positive work attitudes than it would to smart
      pump satisfaction. We also hypothesized that smart pump-specific support would be
      more strongly related to smart pump satisfaction than it would to general
      positive work attitudes. METHODOLOGY: Data were collected in a cross-sectional
      field study via online surveys at two large, public hospital systems in the
      Midwestern United States, one in Iowa (n = 311 nurses) and one in Wisconsin (n =
      346 nurses). Because nurses in one system had more experience with smart pump
      technology than nurses in the other system, analyses were run separately to
      compare results across the two sites. FINDINGS: Consistent with the principle of
      compatibility, hierarchical regression revealed across both sites that smart pump
      support had a stronger relationship with smart pump satisfaction whereas general
      organizational support perceptions had a stronger relationship with general
      positive work attitudes. In addition, moderation effects were present in one
      sample where high levels of the noncompatible support (e.g., smart pump-specific
      support on positive workplace attitudes) buffered low levels of compatible
      support. PRACTICE IMPLICATIONS: Our findings highlight the contextual importance
      of support in regard to the growing technological transformations that health
      care systems currently experience. When specific forms of support are provided
      for specific technologies, end-users will generally respond more favorably
      compared to when general support is the only available resource.

PMID- 26317303
TI  - Evaluating the link between human resource management decisions and patient
      satisfaction with quality of care.
AB  - BACKGROUND: Patient satisfaction with quality of care is becoming increasingly
      important in the competitive hospital market. Simultaneously, the growing
      shortage of clinical staff poses a considerable challenge to ensuring a high
      quality of care. In this context, a question emerges regarding whether and how
      human resource management (HRM) might serve as a means to reduce staff shortage
      problems and to increase patient satisfaction. Although considerable efforts have
      been devoted to understanding the concepts of patient satisfaction and HRM,
      little is known about the interrelationships between these concepts or about the
      link between staff shortage problems and patients' satisfaction with quality of
      care. PURPOSE: The aim of this study was to investigate the relationship between
      strategic human resource management (SHRM), staff shortage problems, and
      patients' satisfaction with care. Furthermore, we analyze how the HRM decision to
      fill short-term vacancies through temporary staffing affects patient
      satisfaction. We differentiate between physicians and nurses. METHODOLOGY: We
      develop and empirically test a theoretical model. The data (n = 165) are derived
      from a survey on SHRM that was sent to 732 German hospitals and from a survey on
      patient satisfaction that comprises 436,848 patient satisfaction ratings. We use
      a structural equation modeling approach to test the model. FINDINGS: The results
      indicate that SHRM significantly reduces staff shortage problems for both
      occupational groups. Having fewer physician shortage problems is significantly
      associated with higher levels of patient satisfaction, whereas this effect is not
      significant for nurses. Furthermore, the use of temporary staffing considerably
      reduces patients' satisfaction with care. PRACTICE IMPLICATIONS: Hospital
      managers are advised to consider the effects of HRM decisions on patients'
      satisfaction with care. In particular, investments in SHRM targeted at physicians
      have significantly positive effects on patient satisfaction, whereas the
      temporary staffing of physicians and nurses should be avoided.

PMID- 26317304
TI  - Balancing cognitive diversity and mutual understanding in multidisciplinary
      teams.
AB  - BACKGROUND: Interprofessional health care teams are increasingly utilized in
      health care organizations. Although there is support for their capacity to solve
      complex problems, there is also evidence that such teams are not always
      successful. In an effort to understand the capacity of interprofessional teams to
      innovate successfully, we investigate the role of cognitive diversity to
      establish whether and how knowledge differences lead to innovation. PURPOSES: The
      aim of this study was to construct and investigate a model of team innovation
      predicted by cognitive diversity. In addition to investigating the direct impact
      of cognitive diversity in interprofessional health care teams, we develop a model
      incorporating mediated and moderated effects. In this study, we explore the role
      of debate as a mediating factor capable of explaining the impact of cognitive
      diversity on innovation. We further propose that the link between cognitive
      diversity and innovation through debate is contingent upon trans-specialist
      knowledge, knowledge shared by health care professionals, spanning specialist
      divides and enabling mutual understanding. METHODOLOGY: The hypotheses were
      investigated using a cross-sectional, correlational design. Survey data received
      from 75 interprofessional teams employed in an acute care setting, representing a
      36% response rate, were used to investigate our model. FINDINGS: Analysis
      supports a significant relationship between cognitive diversity and debate, which
      is stronger when teams rate highly for trans-specialist knowledge. Results also
      support a positive relationship between debate and innovation and our full
      moderated mediated pathway. PRACTICE IMPLICATIONS: A range of strategies are
      indicated by our results to increase innovation in interprofessional teams. In
      particular, interventions such as interprofessional education and training, which
      have been shown to facilitate the development of shared language and meaning, are
      recommended by our findings.

PMID- 26317306
TI  - Prolactin Receptor Expression is an Independent Favorable Prognostic Marker in
      Human Breast Cancer.
AB  - Prolactin (PRL) hormone plays an important role in the development of the mammary
      gland and terminal differentiation of the mammary epithelial cells. While initial
      studies suggested that PRL may contribute to the development of breast cancer
      through PRL/prolactin receptor (PRLR) autocrine function, mounting evidence
      indicate a different role for PRL, highlighting this hormone as a regulator of
      epithelial plasticity and as a potential tumor suppressor. To gain further
      insights into the role of PRL in human breast carcinogenesis,
      immunohistochemistry analyses of PRLR protein expression levels using tissue
      microarray of 102 cases were done in comparison with various clinical/pathologic
      parameters and molecular subtypes. In addition, gene expression level of PRLR was
      also evaluated in relation to intrinsic molecular subtypes, tumor grade, and
      patient outcome using GOBO database for 1881 breast cancer patients.
      Interestingly, PRLR expression was found to be significantly downregulated in
      invasive breast cancer (21.4%) in comparison with normal/benign (80%) and in situ
      carcinoma (60%) (P=0.003498). Moreover, PRLR expression was associated with lymph
      node negativity and low-grade well-differentiated tumors. PRLR expression was
      strongest in luminal A subtype, and was virtually undetectable in the worse
      prognosis triple-negative breast cancer subtype (P=0.00001). Furthermore, PRLR
      expression was independent of ER, PR, HER-2, and P53 status. Finally, PRLR
      expression was significantly (P<0.01) associated with prolonged distant
      metastasis-free survival in breast cancer patients. In conclusion, our results
      highlight PRLR as an independent predictor of favorable prognosis in human breast
      cancer. 

PMID- 26317305
TI  - Development of an automated PD-L1 immunohistochemistry (IHC) assay for non-small
      cell lung cancer.
AB  - Nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune checkpoint
      inhibitor antibody, developed by Bristol-Myers Squibb Inc., has activity across
      non-small cell lung cancer (NSCLC) histologies and is Food and Drug
      Administration approved for treatment of metastatic squamous NSCLC with
      progression on or after platinum-based chemotherapy. PD-L1 has been investigated
      as a potential biomarker to predict clinical response to nivolumab in clinical
      settings. We report an automated PD-L1 immunohistochemistry (IHC) assay, which
      was developed to detect cell surface PD-L1 in formalin-fixed paraffin-embedded
      human tumor tissue specimens using Dako's Autostainer Link 48. The primary
      antibody for this assay is a rabbit monoclonal anti-human PD-L1 antibody, clone
      28-8. The specificity of 28-8 for PD-L1 was demonstrated by antigen competition
      and genetic deletion of PD-L1 in tumor cell lines. The specificity of the PD-L1
      IHC assay was further evaluated in a collection of 30 normal human tissues. The
      PD-L1 IHC assay was optimized for high sensitivity and precision in routine
      application. A pathology scoring and interpretation method specific to nivolumab
      clinical studies was adopted for the assay. The analytical performance of the
      assay was validated for application in the determination of PD-L1 status in human
      NSCLC specimens. The clinical application of the assay and scoring method was
      further validated in 3 Clinical Laboratory Improvement Amendments certified labs.
      The assay is currently being investigated in a variety of clinical studies for
      use as an in vitro diagnostic to select and stratify patients for treatment with
      the anti-PD-1 therapeutic antibody, nivolumab. 

PMID- 26317307
TI  - Merkel Cell Polyomavirus is Not Detected in Lung Adenocarcinomas by
      Immunohistochemistry.
AB  - Merkel cell polyomavirus (MCPyV) is an oncogenic DNA virus that causes Merkel
      cell carcinoma. Recently, MCPyV has been identified in other noncutaneous tumors
      including lung non-small cell carcinoma. However, the true role of this virus in
      lung carcinogenesis is unclear. We aimed to determine the efficacy of
      immunohistochemistry for detecting MCPyV in a series of lung adenocarcinomas.
      Nuclear expression of the MCPyV large T antigen was evaluated by
      immunohistochemistry (CM2B4 antibody) in formalin-fixed paraffin-embedded lung
      adenocarcinomas of different histologic subtypes. Of a total of 90 lung
      adenocarcinomas that were examined, none of the tumors (0%) were positive for
      MCPyV T antigen expression by immunohistochemistry. These data suggest that MCPyV
      immunohistochemistry alone might not be a sensitive method for detection of MCPyV
      in lung adenocarcinomas or that these tumors do not harbor MCPyV. Further studies
      are needed to correlate these data with molecular studies for MCPyV DNA
      integration and to similarly evaluate other types of lung carcinomas.

PMID- 26317308
TI  - Heat-induced Epitope Retrieval for Immunohistochemistry at High Altitude: A
      Quality Assurance Study.
AB  - INTRODUCTION: Heat-induced epitope retrieval (HIER) of formalin-fixed paraffin
      embedded tissues is now a standard practice in immunohistochemistry (IHC). In
      this study, we aimed to test the effect of altering HIER temperature on IHC
      staining quality at high altitude, the hypothesis being that lower HIER
      temperatures would result in improved staining patterns. MATERIALS AND METHODS:
      In a laboratory at high altitude (Aurora, CO), we used a platform with automated
      onboard epitope retrieval, and systematically tested 3 different HIER
      temperatures (100 degrees C, 95 degrees C, 90 degrees C) with 4 IHC stains that
      are commonly used in routine practice: CD3, Ki67, CK20, and Melan A (n=10 for
      each antibody/epitope retrieval temperature combination). A scoring system was
      devised, the slides were scored in a blinded manner, and statistical analysis was
      performed. For comparison, the same study was performed in a laboratory near sea
      level (Atlanta, GA). RESULTS: At high altitude, lower HIER temperatures resulted
      in improved staining patterns, as quantified by stronger staining intensity and
      greater area of the slides stained. The scores obtained with HIER temperatures of
      95 degrees C and 90 degrees C were higher than those obtained with HIER of 100
      degrees C, and the difference was found to be statistically significantly for
      some antibody/epitope retrieval temperature combinations (P<0.05). This effect
      was not seen in the laboratory near sea level. CONCLUSIONS: We show that
      alternate epitope retrieval recommendations are warranted for laboratories at
      high altitude. Furthermore, we suggest that manufactures should consider how
      their instruments will perform at high altitude as they further automate the
      process of IHC.

PMID- 26317309
TI  - BRAF and NRAS Mutations are Not Mutually Exclusive in Melanoma and in Single
      Melanoma Cells.

PMID- 26317310
TI  - HER2 Gene Amplification by Fluorescence In Situ Hybridization (FISH) Compared
      With Immunohistochemistry (IHC) in 122 Equivocal Gastric Cancer Cases.
AB  - OBJECTIVE: To determine the frequency of HER2/neu amplification and the
      relationship between HER2/neu expression and clinicopathologic features in
      gastric cancers scored immunohistochemistry (IHC) 2+. METHODS: A total of 122
      gastric cancer cases scored IHC 2+ were retrospectively analyzed for HER2
      amplification by fluorescence in situ hybridization (FISH). The correlation
      between HER2/neu expression and clinicopathologic features was analyzed. RESULTS:
      HER2/neu gene was amplified in 17 out of the 122 gastric cancer samples. The
      concordance rate between IHC and FISH was 13.9%. HER2/neu status was correlated
      with the age of patients (P<0.05). Polysomy of CEP17 was demonstrated in 46
      cases, 11 of which (23.91%) were amplified for HER2/neu. Within the subgroups, a
      correlation between CEP17 polysomy and the depth of invasion was observed
      (P<0.05). CONCLUSIONS: The results highlight the necessity of FISH test for
      further categorization when gastric cancer cases are scored 2+ by IHC. The value
      of HER2/neu for a potential role as a negative prognostic factor in the equivocal
      gastric cancer cases is limited.

PMID- 26317311
TI  - Application of HER2 CISH pharmDX for DNA Ploidy Determination.
AB  - Products of conception (POC) are encountered daily in general pathology practice.
      The molar workup is an important part of POC examination. Ploidy analysis,
      expressed as DNA index (DI), is part of the pathologic workup of molar pregnancy.
      For the past decade, chromogenic in situ hybridization (CISH) has become a
      popular way to detect HER2 gene amplification. Current study aims to determine
      whether HER2 CISH dual-color assay can be used to determine DI in POCs. Twenty
      two POC cases were chosen from the departmental archives, including 6 complete
      hydatidiform mole (CM), 10 partial mole (PM), and 6 hydropic POC (HP). CISH assay
      was performed using the HER2 CISH PharmDx Kit (SK109; Dako). This kit generates
      red (HER2) and blue (CEN-17) chromogenic signals on the same tissue section. In
      the 10 triploid PM cases, CISH generated HER2 signal value of 2.925+/-0.19. Nine
      cases (90%) had values within this range, except 1 case (2.5). In diploid cases,
      CISH generated HER2 signal value of 2.063+/-0.19. Results from 11 (91.7%) cases
      fell within this range, except 1 HP case (2.35). Sensitivity is 90%, specificity
      91.6%, and overall accuracy 90.9%. The current study is the first one that
      demonstrates HER2/CEN-17 dual-color CISH can be used for microscopic analysis of
      cell ploidy. This technique provides a relatively easy and straight way to access
      DI using regular bright-field microscope. Concurrent CEN-17 signal and ploidy in
      both placental and maternal tissue can be used as internal control. This assay
      can be performed in any laboratory that can perform immunohistochemistry.

PMID- 26317312
TI  - The Utility of GATA3 in the Diagnosis of Urothelial Carcinomas With Variant
      Morphologic Patterns.
AB  - The transcription factor GATA3 is a recently described biomarker that is highly
      expressed in bladder and breast carcinomas. Although it has shown sensitivity as
      a marker of primary bladder carcinomas with purely urothelial differentiation,
      the ability of GATA3 to label primary bladder carcinomas with variant morphologic
      patterns has been incompletely assessed to date. The current study was designed
      to determine whether GATA3 staining is retained in "unconventional" bladder
      carcinomas. Eighty-eight cases of primary bladder cancers were retrieved from the
      authors' institutional archive, and they included the following histomorphologic
      types: 6 small cell carcinomas, 12 sarcomatoid carcinomas, 17 adenocarcinomas
      (both primary and urothelial variants with glandular differentiation), 24
      micropapillary carcinomas, and 27 squamous cell carcinomas (both primary and
      urothelial variants with squamous differentiation). A tissue microarray was
      constructed and automated immunostaining for GATA3 (Clone L50-823, Biocare
      Medical, Concord, CA) was performed using standard technique. Among the 5
      variants of unconventional bladder carcinoma, only the micropapillary and
      sarcomatoid forms exhibited consistent and strong immunolabeling for GATA3.
      Hence, the sensitivity of this determinant is diminished in several histologic
      forms of primary bladder carcinoma. That fact will affect the interpretation of
      GATA3 stains in the context of possible metastasis from primary bladder
      carcinomas with variant morphologic patterns, as well as their distinction from
      secondary bladder involvement by tumors of nonurothelial origin.

PMID- 26317313
TI  - Her2 and Ki67 Biomarkers Predict Recurrence of Ductal Carcinoma in Situ.
AB  - BACKGROUND: A subset of patients with ductal carcinoma in situ (DCIS) experience
      recurrence or progression to invasive cancer. Current clinical practice is not
      reliably guided by DCIS recurrence prediction, although recurrence risk for
      invasive breast cancer can now be assessed. We analyzed a panel of biomarkers
      (estrogen receptor, Her2, Ki67, p53, cyclin D1, COX-2, caveolin-1, survivin, and
      PPAR-gamma) and DCIS histologic and clinical features to determine associations
      with DCIS recurrence. MATERIALS AND METHODS: Seventy DCIS cases diagnosed between
      1995 and 2010 were divided into 2 groups: 52 had DCIS without known recurrence
      after excision and 18 had DCIS with subsequent recurrence after excision as DCIS
      or invasive carcinoma in the ipsilateral or contralateral breast. Tissue
      microarrays were prepared, immunohistochemistry performed, and expression of the
      biomarkers scored semiquantitatively. Variables analyzed included age, tumor
      size, margin status, DCIS grade, necrosis, histologic type, and
      immunohistochemistry scores. Differences between groups were evaluated using t
      tests for continuous variables and Fisher exact tests for categorical variables.
      RESULTS: Intraductal necrosis was associated with increased recurrence risk: 46%
      of nonrecurrent cases showed necrosis compared with 83% of those who recurred
      (P=0.007). Her2 (human epidermal growth factor receptor 2) and Ki67 expression
      distributions were significantly different between nonrecurrent and recurrent
      cases. Her2 was overexpressed in 14% of nonrecurrent cases compared with 50% in
      the recurrent cases (P=0.03). A total of 87% of nonrecurrent cases had low Ki67
      staining (0% to 10%) compared with 50% among the recurrent cases (P=0.002).
      CONCLUSION: Our results suggest that Her2 and Ki67 immunohistochemistry and the
      presence of intraductal necrosis aid in DCIS risk stratification.

PMID- 26317314
TI  - Increased FLI-1 Expression is Associated With Poor Prognosis in Non-Small Cell
      Lung Cancers.
AB  - Friend leukemia integration-1 (FLI-1) antibody, a commercially available antibody
      directed against the C-terminus of FLI-1 protein-binding domain, has been used as
      a useful tool in the differential diagnosis of small blue round cell tumors and
      vascular neoplasms, but shows inconsistent expression in lung cancers. The aims
      of this study were to evaluate FLI-1 immunohistochemical expression in non-small
      cell lung cancer (NSCLC), and its relationships between the clinicopathologic
      parameters and prognosis. We investigated the FLI-1 expression in 108 cases of
      NSCLC by using multiple tumor microarrays. Correlations between the FLI-1
      expression and clinicopathologic parameters and prognostic significance were
      analyzed. The effect of FLI-1 expression on survival is estimated by Kaplan-Meier
      survival analysis and Cox proportional hazards models. Our results revealed that
      patients with high FLI-1 expression had shorter overall survival (P=0.014) than
      those with low FLI-1 expression. In multivariate analysis, FLI-1 was confirmed as
      an independent poor prognostic factor in NSCLC (overall survival: hazard ratio,
      7.292; 95% confidence interval, 0.294-0.823; P=0.007). In conclusion, this study
      shows that FLI-1 is expressed variably in different subtypes of NSCLC, and its
      expression is related to clinicopathologic parameters and poorer prognosis.
      However, further studies are required to elucidate its function in tumorigenesis
      of NSCLC.

PMID- 26317315
TI  - Where the Sun Shines: Industry's Payments to Transplant Surgeons.
AB  - The Open Payments Program (OPP) was recently implemented to publicly disclose
      industry payments to physicians, with the goal of enabling patient awareness of
      potential conflicts of interests. Awareness of OPP, its data, and its
      implications for transplantation are critical. We used the first wave of OPP data
      to describe industry payments made to transplant surgeons. Transplant surgeons (N
      = 297) received a total of $759 654. The median (interquartile range [IQR])
      payment to a transplant surgeon was $125 ($39-1018), and the highest payment to
      an individual surgeon was $83 520; 122 surgeons received <$100, and 17 received
      >$10 000. A higher h-index was associated with 30% higher chance of receiving
      >$1000 (relative risk/10 unit h-index increase = 1.18 1.301.44 , p < 0.001). The
      highest payment category was consulting fees, with a total of $314 448 paid in
      this reported category. Recipients of consulting fees had higher h-indices,
      median (IQR) of 20 (10-35) versus nine (3-17) (p < 0.001). Ten of 122 companies
      accounted for 62% of all payments. Kidney transplant and liver transplant (LT)
      centers that received >$1000 had higher center volumes (p < 0.001). LT centers
      that received payments of >$1000 had a higher percentage of private
      insurance/self-pay patients (p < 0.01). Continued surveillance of industry
      payments may further elucidate the relationship between industry payments and
      physician practices. 

PMID- 26317316
TI  - Effect of Cognitive Load on Seating Posture in Children.
AB  - Although children are frequently required to sit upright, it is often difficult
      to maintain this posture when performing cognitive tasks. Information about the
      relationship between a cognitive tasks and postural seating control is important
      for children to complete tasks more effectively. To determine the muscle activity
      and body sway of children in a seated posture while performing a cognitive task,
      changes in muscle activity and center of pressure (COP) were recorded while 4(th)
      grade children performed arithmetic tasks. Electromyography was recorded from the
      internal oblique and lumbar multifidus muscles, and the COP was recorded using a
      baropodometer placed on the stool. These variables were measured during easy (EA)
      and difficult (DA) arithmetic tasks. EMG activity decreased during the EA and DA
      tasks, while the COP was displaced in the DA task. The results of the arithmetic
      tasks were not related to the EMG or COP changes. Attention to maintain a seated
      posture may be reduced when children perform cognitive tasks. Therefore, it may
      be better to allow children to alter their posture especially when they are
      performing difficult tasks. In this research, we only used arithmetic tasks as
      the cognitive exercise, and therefore, other types of tasks should be examined.

PMID- 26317317
TI  - Synthesis of Uniform, Monodisperse, Sophorolipid Twisted Ribbons.
AB  - Control over size monodispersity in chiral self-assembled systems is important
      for potential applications like templating, tissue engineering or
      enantioselective chromatography, just to cite a few examples. In this context, it
      was reported that the saturated form of sophorolipids (SL), a bioderived
      glycolipid, are able to form self-assembled twisted ribbons in water at neutral
      pH. Here, we show the possibility to control their size dispersion, generally
      between 10 and 40 nm after synthesis to a value of 13.5+/-1.5 nm, by a simple
      dialysis step eliminating the excess of NaCl. We use transmission electron
      microscopy under cryogenic conditions (cryo-TEM) combined with small angle
      neutron scattering (SANS) to characterize the ribbon dispersion both visually and
      statistically. Two negative controls show the importance of salt in the
      aggregation process of the ribbons.

PMID- 26317318
TI  - Sensory and Functionality Differences of Whey Protein Isolate Bleached by
      Hydrogen or Benzoyl Peroxide.
AB  - Whey protein is a highly functional food ingredient used in a wide variety of
      applications. A large portion of fluid whey produced in the United States is
      derived from Cheddar cheese manufacture and contains annatto (norbixin), and
      therefore must be bleached. The objective of this study was to compare sensory
      and functionality differences between whey protein isolate (WPI) bleached by
      benzoyl peroxide (BP) or hydrogen peroxide (HP). HP and BP bleached WPI and
      unbleached controls were manufactured in triplicate. Descriptive sensory analysis
      and gas chromatography-mass spectrometry were conducted to determine flavor
      differences between treatments. Functionality differences were evaluated by
      measurement of foam stability, protein solubility, SDS-PAGE, and effect of NaCl
      concentration on gelation relative to an unbleached control. HP bleached WPI had
      higher concentrations of lipid oxidation and sulfur containing volatile compounds
      than both BP and unbleached WPI (P < 0.05). HP bleached WPI was characterized by
      high aroma intensity, cardboard, cabbage, and fatty flavors, while BP bleached
      WPI was differentiated by low bitter taste. Overrun and yield stress were not
      different among WPI (P < 0.05). Soluble protein loss at pH 4.6 of WPI decreased
      by bleaching with either hydrogen peroxide or benzoyl peroxide (P < 0.05), and
      the heat stability of WPI was also distinct among WPI (P < 0.05). SDS PAGE
      results suggested that bleaching of whey with either BP or HP resulted in protein
      degradation, which likely contributed to functionality differences. These results
      demonstrate that bleaching has flavor effects as well as effects on many of the
      functionality characteristics of whey proteins. PRACTICAL APPLICATIONS: Whey
      protein isolate (WPI) is often used for its functional properties, but the effect
      of oxidative bleaching chemicals on the functional properties of WPI is not
      known. This study identifies the effects of hydrogen peroxide and benzoyl
      peroxide on functional and flavor characteristics of WPI bleached by hydrogen and
      benzoyl peroxide and provides insights for the product applications which may
      benefit from bleaching.

PMID- 26317319
TI  - Morphological and functional characterization of human induced pluripotent stem
      cell-derived neurons (iCell Neurons) in defined culture systems.
AB  - Pre-clinical testing of drug candidates in animal models is expensive, time
      consuming, and often fails to predict drug effects in humans. Industry and
      academia alike are working to build human-based in vitro test beds and advanced
      high throughput screening systems to improve the translation of preclinical
      results to human drug trials. Human neurons derived from induced pluripotent
      stems cells (hiPSCs) are readily available for use within these test-beds and
      high throughput screens, but there remains a need to robustly evaluate cellular
      behavior prior to their incorporation in such systems. This study reports on the
      characterization of one source of commercially available hiPSC-derived neurons,
      iCell((r)) Neurons, for their long-term viability and functional performance to
      assess their suitability for integration within advanced in vitro platforms. The
      purity, morphology, survival, identity, and functional maturation of the cells
      utilizing different culture substrates and medium combinations were evaluated
      over 28 days in vitro (DIV). Patch-clamp electrophysiological data demonstrated
      increased capacity for repetitive firing of action potentials across all culture
      conditions. Significant differences in cellular maturity, morphology, and
      functional performance were observed in the different conditions, highlighting
      the importance of evaluating different surface types and growth medium
      compositions for application in specific in vitro protocols.

PMID- 26317320
TI  - Population pharmacokinetics of naloxegol in a population of 1247 healthy subjects
      and patients.
AB  - AIMS: Naloxegol, a polyethylene glycol conjugated derivative of the opioid
      antagonist naloxone, is in clinical development for treatment of opioid-induced
      constipation (OIC). The aim of the study was to develop a population
      pharmacokinetic model describing the concentration vs. time profile of orally
      administered naloxegol, and determine the impact of pre-specified demographic and
      clinical factors and concomitant medication on population estimates of apparent
      clearance (CL/F) and apparent central compartment volume of distribution (Vc /F).
      METHODS: Analysis included 12,844 naloxegol plasma concentrations obtained from
      1247 healthy subjects, patients with non-OIC and patients with OIC in 14 phase 1,
      2b and 3 clinical studies. Pharmacokinetic analysis used the non-linear mixed
      effects modelling program. Goodness of fit plots and posterior predictive checks
      were conducted to confirm concordance with observed data. RESULTS: The final
      model was a two compartment disposition model with dual absorptions, comprising
      one first order absorption (ka1 4.56 h(-1) ) and one more complex absorption with
      a transit compartment (ktr 2.78 h(-1) ). Mean (SE) parameter estimates for CL/F
      and Vc /F, the parameters assessed for covariate effects, were 115 (3.41) l h(-1)
      and 160 (27.4) l, respectively. Inter-individual variability was 48% and 51%,
      respectively. Phase of study, gender, race, concomitant strong or moderate CYP3A4
      inhibitors, strong CYP3A4 inducers, P-glycoprotein inhibitors or inducers,
      naloxegol formulation, baseline creatinine clearance and baseline opioid dose had
      a significant effect on at least one pharmacokinetic parameter. Simulations
      indicated concomitant strong CYP3A4 inhibitors or inducers had relevant effects
      on naloxegol exposure. CONCLUSIONS: Administration of strong CYP3A4 inhibitors or
      inducers had a clinically relevant influence on naloxegol pharmacokinetics.

PMID- 26317321
TI  - Development and validation of a rapid LC-MS/MS method to quantify letrozole in
      human plasma and its application to therapeutic drug monitoring.
AB  - A selective, rapid, and sensitive liquid chromatography-tandem mass
      spectrometry(LC-MS/MS) method was developed and validated for the determination
      of letrozole (LTZ) in human plasma, using anastrozole as internal standard (IS).
      Sample preparation was performed by one-step protein precipitation with methanol.
      The analyte and IS were chromatographed on a reversed-phase YMC-ODS-C18 column
      (2.0 * 100 mm i.d., 3 um) with a flow rate of 0.3 mL/min. The mobile phase
      consisted of water containing 0.1% formic acid (v/v) and methanol containing 0.1%
      formic acid (v/v). The mass spectrometer was operated in selected reaction
      monitoring mode through electrospray ionization ion mode using the transitions of
      m/z 286.2 -> 217.1 for LTZ and m/z 294.1 -> 225.1 for IS, respectively. The
      method was validated for selectivity, linearity, lower limit of quantitation,
      precision, accuracy, matrix effects and stability in accordance with the US Food
      and Drug Administration guidelines. Linear calibration curves were 1.0-60.0
      ng/mL. Intra- and inter-batch precision (CV) for LTZ were <9.34%, and the
      accuracy ranged from 97.43 to 105.17%. This method was successfully used for the
      analysis of samples from patients treated with LTZ in the dose of 2.5 mg/day. It
      might be suitable for therapeutic drug monitoring of these patients and
      contribute to predict the risk of adverse reactions.

PMID- 26317323
TI  - Perceptual learning eases crowding by reducing recognition errors but not
      position errors.
AB  - When an observer reports a letter flanked by additional letters in the visual
      periphery, the response errors (the crowding effect) may result from failure to
      recognize the target letter (recognition errors), from mislocating a correctly
      recognized target letter at a flanker location (target misplacement errors), or
      from reporting a flanker as the target letter (flanker substitution errors).
      Crowding can be reduced through perceptual learning. However, it is not known how
      perceptual learning operates to reduce crowding. In this study we trained
      observers with a partial-report task (Experiment 1), in which they reported the
      central target letter of a three-letter string presented in the visual periphery,
      or a whole-report task (Experiment 2), in which they reported all three letters
      in order. We then assessed the impact of training on recognition of both
      unflanked and flanked targets, with particular attention to how perceptual
      learning affected the types of errors. Our results show that training improved
      target recognition but not single-letter recognition, indicating that training
      indeed affected crowding. However, training did not reduce target misplacement
      errors or flanker substitution errors. This dissociation between target
      recognition and flanker substitution errors supports the view that flanker
      substitution may be more likely a by-product (due to response bias), rather than
      a cause, of crowding. Moreover, the dissociation is not consistent with
      hypothesized mechanisms of crowding that would predict reduced positional errors.

PMID- 26317322
TI  - Subgroup analysis of East Asians in RAINBOW: A phase 3 trial of ramucirumab plus
      paclitaxel for advanced gastric cancer.
AB  - BACKGROUND AND AIM: East Asia has higher gastric cancer incidence and mortality
      rates than other regions. We present a subgroup analysis of East Asians in the
      positive study RAINBOW. METHODS: Patients with advanced gastric or
      gastroesophageal junction adenocarcinoma previously treated with platinum and
      fluoropyrimidine received ramucirumab 8 mg/kg or placebo on days 1 and 15 plus
      paclitaxel 80 mg/m(2) on days 1, 8, and 15 of a 28-day cycle. RESULTS: Of 665
      intention-to-treat patients, 223 were East Asian. Median overall survival was
      12.1 months for ramucirumab plus paclitaxel and 10.5 months for placebo plus
      paclitaxel (hazard ratio: 0.986, 95% confidence interval: 0.727-1.337, P =
      0.929). Median progression-free survival was 5.5 months for ramucirumab plus
      paclitaxel and 2.8 months for placebo plus paclitaxel (hazard ratio: 0.628, 95%
      confidence interval: 0.473-0.834, P = 0.001). Objective response rates were 34%
      for ramucirumab plus paclitaxel and 20% for placebo plus paclitaxel. Grade >= 3
      neutropenia (60% vs 28%) and leukopenia (34% vs 13%) were higher for ramucirumab
      plus paclitaxel. The rate of febrile neutropenia was low (4% vs 4%). Special
      interest adverse events included any grade bleeding/hemorrhage (55% vs 25%),
      proteinuria (27% vs 7%), and hypertension (22% vs 2%). CONCLUSIONS: Ramucirumab
      plus paclitaxel significantly improves progression-free survival and response
      rate, with prolonged median overall survival and an acceptable safety profile in
      East Asians with advanced gastric cancer.

PMID- 26317324
TI  - The effects of grouping on speed discrimination thresholds in adults, typically
      developing children, and children with autism.
AB  - Adult observers show elevated speed discrimination thresholds when comparing the
      speeds of objects moving across a boundary compared to those moving parallel to a
      boundary (Verghese & McKee, 2006)-an effect that has been attributed to grouping
      processes in conjunction with a prior for smooth motion. Here, we extended
      Verghese and McKee's (2006) paradigm to typically developing children (n = 35)
      and children with autism (n = 26) and compared their performance with that of
      typical adults (n = 19). Speed discrimination thresholds were measured in three
      conditions: (a) with dots moving parallel to a boundary, (b) with dots moving
      perpendicular to a boundary, and (c) with dots in each stimulus half moving in
      orthogonal, oblique directions. As expected, participants had higher speed
      discrimination thresholds when dots appeared to cross a boundary compared to when
      dots moved parallel to the boundary. However, participants had even higher
      thresholds when dots moved in oblique, orthogonal directions, where grouping
      should be minimal. All groups of participants showed a similar pattern of
      performance across conditions although children had higher thresholds than adult
      participants overall. We consider various explanations for the pattern of
      performance obtained, including enhanced sensitivity for shearing motions and
      reduced sensitivity for discriminating different directions. Our results
      demonstrate that the speed discrimination judgments of typically developing
      children and children with autism are similarly affected by spatial configuration
      as those of typical adults and provide further evidence that speed discrimination
      is unimpaired in children with autism. 

PMID- 26317325
TI  - Synthesis and Linear and Nonlinear Optical Properties of Three Push-Pull Oxazol
      5(4H)-one Compounds.
AB  - Three uncharged push-pull oxazol-5(4H)-ones were synthesized and thoroughly
      characterized. The examined molecules contained electron-donor and electron
      acceptor groups interacting via a pi-conjugated bridge. Spectral properties of
      the oxazol-5(4H)-ones were studied in detail in three solvents of different
      polarities. The results indicate a solvatochromic shift toward lower energy for
      the charge-transfer state. The compounds are weakly fluorescent in polar
      solvents, but they have high fluorescence quantum yields in nonpolar solvents.
      Their two-photon absorption (2PA) properties were characterized by the open- and
      closed-aperture Z-scan technique, by the pump-probe technique, and by the two
      photon excited fluorescence method. The dyes exhibit relatively high effective
      two-photon absorption cross sections ranging from 490 to 2600 GM at ~100
      GW/cm(2), according to the Z-scan results, which are found, however, to contain
      significant contribution from higher-order absorption processes. In addition,
      these compounds display good photostability.

PMID- 26317326
TI  - Multifunctional Chitosan-45S5 Bioactive Glass-Poly(3-hydroxybutyrate-co-3
      hydroxyvalerate) Microsphere Composite Membranes for Guided Tissue/Bone
      Regeneration.
AB  - Novel multifunctional chitosan-45S5 bioactive glass-poly(3-hydroxybutyrate-co-3
      hydroxyvalerate) (PHBV) microsphere (CS-BG-MS) composite membranes were developed
      with applicability in guided tissue/bone regeneration (GTR/GBR). The
      incorporation of 45S5 BG and PHBV MS into CS membranes not only provided the
      membranes with favorable surface roughness, hydrophilicity, and flexibility but
      also slowed down their degradation rate. Moreover, the CS membranes became
      bioactive after the incorporation of 45S5 BG and capable of releasing drugs of
      different physicochemical properties in a controlled and sustained manner with
      the addition of PHBV MS. Cell culture tests showed that osteoblast-like MG-63
      human osteosarcoma cells had significantly higher adhesion, cell proliferation,
      and alkaline phosphatase (ALP) activity on CS-BG and CS-BG-MS membranes than on
      neat CS membranes. Therefore, the developed bioactive CS-BG-MS membranes with
      potential multidrug (e.g., antibacterial and antiosteoporosis drugs) delivery
      capability are promising candidate membranes for GTR/GBR applications. 

PMID- 26317327
TI  - Toxicity inhibitors protect lipid membranes from disruption by Abeta42.
AB  - Although the precise molecular factors linking amyloid beta-protein (Abeta) to
      Alzheimer's disease (AD) have not been deciphered, interaction of Abeta with
      cellular membranes has an important role in the disease. However, most
      therapeutic strategies targeting Abeta have focused on interfering with Abeta
      self-assembly rather than with its membrane interactions. Here, we studied the
      impact of three toxicity inhibitors on membrane interactions of Abeta42, the
      longer form of Abeta, which is associated most strongly with AD. The inhibitors
      included the four-residue C-terminal fragment Abeta(39-42), the polyphenol (-)
      epigallocatechin-3-gallate (EGCG), and the lysine-specific molecular tweezer,
      CLR01, all of which previously were shown to disrupt different steps in Abeta42
      self-assembly. Biophysical experiments revealed that incubation of Abeta42 with
      each of the three modulators affected membrane interactions in a distinct manner.
      Interestingly, EGCG and CLR01 were found to have significant interaction with
      membranes themselves. However, membrane bilayer disruption was reduced when the
      compounds were preincubated with Abeta42, suggesting that binding of the assembly
      modulators to the peptide attenuated their membrane interactions. Importantly,
      our study reveals that even though the three tested compounds affect Abeta42
      assembly differently, membrane interactions were significantly inhibited upon
      incubation of each compound with Abeta42, suggesting that preventing the
      interaction of Abeta42 with the membrane contributes substantially to inhibition
      of its toxicity by each compound. The data suggest that interference with
      membrane interactions is an important factor for Abeta42 toxicity inhibitors and
      should be taken into account in potential therapeutic strategies, in addition to
      disruption or remodeling of amyloid assembly. 

PMID- 26317328
TI  - Syringe Injectable Electronics: Precise Targeted Delivery with Quantitative
      Input/Output Connectivity.
AB  - Syringe-injectable mesh electronics with tissue-like mechanical properties and
      open macroporous structures is an emerging powerful paradigm for mapping and
      modulating brain activity. Indeed, the ultraflexible macroporous structure has
      exhibited unprecedented minimal/noninvasiveness and the promotion of attractive
      interactions with neurons in chronic studies. These same structural features also
      pose new challenges and opportunities for precise targeted delivery in specific
      brain regions and quantitative input/output (I/O) connectivity needed for
      reliable electrical measurements. Here, we describe new results that address in a
      flexible manner both of these points. First, we have developed a controlled
      injection approach that maintains the extended mesh structure during the "blind"
      injection process, while also achieving targeted delivery with ca. 20 MUm spatial
      precision. Optical and microcomputed tomography results from injections into
      tissue-like hydrogel, ex vivo brain tissue, and in vivo brains validate our basic
      approach and demonstrate its generality. Second, we present a general strategy to
      achieve up to 100% multichannel I/O connectivity using an automated conductive
      ink printing methodology to connect the mesh electronics and a flexible flat
      cable, which serves as the standard "plug-in" interface to measurement
      electronics. Studies of resistance versus printed line width were used to
      identify optimal conditions, and moreover, frequency-dependent noise measurements
      show that the flexible printing process yields values comparable to commercial
      flip-chip bonding technology. Our results address two key challenges faced by
      syringe-injectable electronics and thereby pave the way for facile in vivo
      applications of injectable mesh electronics as a general and powerful tool for
      long-term mapping and modulation of brain activity in fundamental neuroscience
      through therapeutic biomedical studies. 

PMID- 26317329
TI  - Electric Double-Layer Interaction between Dissimilar Charge-Conserved Conducting
      Plates.
AB  - Small metallic particles used in forming nanostructured to impart novel optical,
      catalytic, or tribo-rheological can be modeled as conducting particles with
      equipotential surfaces that carry a net surface charge. The value of the surface
      potential will vary with the separation between interacting particles, and in the
      absence of charge-transfer or electrochemical reactions across the particle
      surface, the total charge of each particle must also remain constant. These two
      physical conditions require the electrostatic boundary condition for metallic
      nanoparticles to satisfy an equipotential whole-of-particle charge conservation
      constraint that has not been studied previously. This constraint gives rise to a
      global charge conserved constant potential boundary condition that results in
      multibody effects in the electric double-layer interaction that are either absent
      or are very small in the familiar constant potential or constant charge or
      surface electrochemical equilibrium condition. 

PMID- 26317330
TI  - Comparison of Experimental and Theoretical Heterogeneous Nucleation on Ultrafine
      Carbon Particles.
AB  - Using a modified turbulent mixing CNC, the heterogeneous nucleation of different
      compounds (working fluids) on nanometer sized carbon particles was examined. The
      working fluids were dibutyl phthalate, octadecane, octadecanol, and octadecanoic
      acid. Based on the particle size distributions measured with a scanning mobility
      particle sizer system, nucleation and consequent growth were examined with
      respect to different temperature and vapor pressure for each working fluid.
      Nucleation rates for all conditions were calculated from the fitted size
      distribution data by subtracting the residual nonactivated particle concentration
      for each condition. Experimental nucleation rates were compared to the calculated
      ones based on Fletcher's heterogeneous nucleation theory. This theory matches
      well with the experiments with octadecanol and octadecanoic acid, and at high
      supersaturation ratios for dibutyl phthalate. However, the theory shows
      discrepancies with the observed phenomena at low supersaturation for dibutyl
      phthalate, and especially for octadecane. Several possible hypotheses for the
      discrepancies and observed particle growth are discussed. 

PMID- 26317332
TI  - Genome-wide Association Mapping of Quantitative Trait Loci (QTLs) for Contents of
      Eight Elements in Brown Rice (Oryza sativa L.).
AB  - An association mapping of quantitative trait loci (QTLs) regulating the
      concentrations of eight elements in brown rice (Oryza sativa L.) was performed
      using USDA mini-core subset cultivated in two different environments. In
      addition, correlation between the grain elemental concentrations was also
      studied. A total of 60 marker loci associated with 8 grain elemental
      concentrations were identified, and these loci were clustered into 37 genomic
      regions. Twenty new QTLs were found to be associated with important elements such
      as Zn, Fe, and P, along with others. Fe concentration was associated with the
      greatest number of markers in two environments. In addition, several important
      elemental/metal transporter genes were identified in a few mapped regions.
      Positive correlation was observed within all grain elemental concentrations. In
      summary, the results provide insight into the genetic basis of rice grain element
      accumulation and may help in the identification of genes associated with the
      accumulation of Zn, Fe, and other essential elements in rice. 

PMID- 26317333
TI  - Sulfamerazine: Understanding the Influence of Slip Planes in the Polymorphic
      Phase Transformation through X-Ray Crystallographic Studies and ab Initio Lattice
      Dynamics.
AB  - Understanding the polymorphism exhibited by organic active-pharmaceutical
      ingredients (APIs), in particular the relationships between crystal structure and
      the thermodynamics of polymorph stability, is vital for the production of more
      stable drugs and better therapeutics, and for the economics of the pharmaceutical
      industry in general. In this article, we report a detailed study of the structure
      property relationships among the polymorphs of the model API, Sulfamerazine.
      Detailed experimental characterization using synchrotron radiation is
      complemented by computational modeling of the lattice dynamics and mechanical
      properties, in order to study the origin of differences in millability and to
      investigate the thermodynamics of the phase equilibria. Good agreement is
      observed between the simulated phonon spectra and mid-infrared and Raman spectra.
      The presence of slip planes, which are found to give rise to low-frequency
      lattice vibrations, explains the higher millability of Form I compared to Form
      II. Energy/volume curves for the three polymorphs, together with the temperature
      dependence of the thermodynamic free energy computed from the phonon frequencies,
      explains why Form II converts to Form I at high temperature, whereas Form III is
      a rare polymorph that is difficult to isolate. The combined experimental and
      theoretical approach employed here should be generally applicable to the study of
      other systems that exhibit polymorphism. 

PMID- 26317331
TI  - 6-Substituted Pyrrolo[2,3-d]pyrimidine Thienoyl Regioisomers as Targeted
      Antifolates for Folate Receptor alpha and the Proton-Coupled Folate Transporter
      in Human Tumors.
AB  - 2-Amino-4-oxo-6-substituted-pyrrolo[2,3-d]pyrimidine antifolate thiophene
      regioisomers of AGF94 (4) with a thienoyl side chain and three-carbon bridge
      lengths [AGF150 (5) and AGF154 (7)] were synthesized as potential antitumor
      agents. These analogues inhibited proliferation of Chinese hamster ovary (CHO)
      sublines expressing folate receptors (FRs) alpha or beta (IC50s < 1 nM) or the
      proton-coupled folate transporter (PCFT) (IC50 < 7 nM). Compounds 5 and 7
      inhibited KB, IGROV1, and SKOV3 human tumor cells at subnanomolar concentrations,
      reflecting both FRalpha and PCFT uptake. AGF152 (6) and AGF163 (8), 2,4-diamino-5
      substituted-furo[2,3-d]pyrimidine thiophene regioisomers, also inhibited growth
      of FR-expressing CHO and KB cells. All four analogues inhibited glycinamide
      ribonucleotide formyltransferase (GARFTase). Crystal structures of human GARFTase
      complexed with 5 and 7 were reported. In severe combined immunodeficient mice
      bearing SKOV3 tumors, 7 was efficacious. The selectivity of these compounds for
      PCFT and for FRalpha and beta over the ubiquitously expressed reduced folate
      carrier is a paradigm for selective tumor targeting. 

PMID- 26317334
TI  - Effectiveness of Trivalent Inactivated Influenza Vaccine in Children Estimated by
      a Test-Negative Case-Control Design Study Based on Influenza Rapid Diagnostic
      Test Results.
AB  - We assessed vaccine effectiveness (VE) against medically attended, laboratory
      confirmed influenza in children 6 months to 15 years of age in 22 hospitals in
      Japan during the 2013-14 season. Our study was conducted according to a test
      negative case-control design based on influenza rapid diagnostic test (IRDT)
      results. Outpatients who came to our clinics with a fever of 38  degrees C or
      over and had undergone an IRDT were enrolled in this study. Patients with
      positive IRDT results were recorded as cases, and patients with negative results
      were recorded as controls. Between November 2013 and March 2014, a total of 4727
      pediatric patients (6 months to 15 years of age) were enrolled: 876 were positive
      for influenza A, 66 for A(H1N1)pdm09 and in the other 810 the subtype was
      unknown; 1405 were positive for influenza B; and 2445 were negative for
      influenza. Overall VE was 46% (95% confidence interval [CI], 39-52). Adjusted VE
      against influenza A, influenza A(H1N1)pdm09, and influenza B was 63% (95% CI, 56
      69), 77% (95% CI, 59-87), and 26% (95% CI, 14-36), respectively. Influenza
      vaccine was not effective against either influenza A or influenza B in infants 6
      to 11 months of age. Two doses of influenza vaccine provided better protection
      against influenza A infection than a single dose did. VE against hospitalization
      influenza A infection was 76%. Influenza vaccine was effective against influenza
      A, especially against influenza A(H1N1)pdm09, but was much less effective against
      influenza B.

PMID- 26317335
TI  - CD8+ T Cell Response to Gammaherpesvirus Infection Mediates Inflammation and
      Fibrosis in Interferon Gamma Receptor-Deficient Mice.
AB  - Idiopathic pulmonary fibrosis (IPF), one of the most severe interstitial lung
      diseases, is a progressive fibrotic disorder of unknown etiology. However, there
      is growing appreciation for the role of viral infection in disease induction
      and/or progression. A small animal model of multi-organ fibrosis, which involves
      murine gammaherpesvirus (MHV68) infection of interferon gamma receptor deficient
      (IFNgammaR-/-) mice, has been utilized to model the association of
      gammaherpesvirus infections and lung fibrosis. Notably, several MHV68 mutants
      which fail to induce fibrosis have been identified. Our current study aimed to
      better define the role of the unique MHV68 gene, M1, in development of pulmonary
      fibrosis. We have previously shown that the M1 gene encodes a secreted protein
      which possesses superantigen-like function to drive the expansion and activation
      of Vbeta4+ CD8+ T cells. Here we show that M1-dependent fibrosis is correlated
      with heightened levels of inflammation in the lung. We observe an M1-dependent
      cellular infiltrate of innate immune cells with most striking differences at 28
      days-post infection. Furthermore, in the absence of M1 protein expression we
      observed reduced CD8+ T cells and MHV68 epitope specific CD8+ T cells to the
      lungs-despite equivalent levels of viral replication between M1 null and wild
      type MHV68. Notably, backcrossing the IFNgammaR-/- onto the Balb/c background,
      which has previously been shown to exhibit weak MHV68-driven Vbeta4+ CD8+ T cell
      expansion, eliminated MHV68-induced fibrosis-further implicating the activated
      Vbeta4+ CD8+ T cell population in the induction of fibrosis. We further addressed
      the role that CD8+ T cells play in the induction of fibrosis by depleting CD8+ T
      cells, which protected the mice from fibrotic disease. Taken together these
      findings are consistent with the hypothesized role of Vbeta4+ CD8+ T cells as
      mediators of fibrotic disease in IFNgammaR-/- mice. 

PMID- 26317336
TI  - Do Hypertensive Individuals Who Are Aware of Their Disease Follow Lifestyle
      Recommendations Better than Those Who Are Not Aware?
AB  - Lifestyle modification is the first step in hypertension management. Our
      objective was to assess adherence to lifestyle recommendations by individuals who
      were aware of their hypertension and to identify characteristics associated with
      non-adherence. Using data from the Korea National Health and Nutrition
      Examination Survey conducted in 2010-2012, we compared the adherence to six
      lifestyle recommendations of hypertensive subjects aware of the status of their
      condition with that of those who were not aware, based on survey regression
      analysis. The characteristics associated with non-adherence were assessed by
      multiple logistic regression analysis. Of all hypertensive subjects, <20% adhered
      to a healthy diet and reduced salt intake and about 80% moderated alcohol
      consumption and did not smoke. Half of all subjects maintained normal body weight
      and engaged in physical activity. Most lifestyle features of aware hypertensive
      Koreans did not differ greatly from those of hypertensive individuals who were
      not aware. Reduction in salt intake was slightly more prevalent among those aware
      of their hypertensive status. Obesity was more prevalent among the aware
      hypertensive subjects, and the prevalence of obesity increased with the duration
      of hypertension. Male gender, younger age, residence in a rural area, low income,
      and the use of antihypertensive medication were associated with non-adherence to
      lifestyle recommendations by hypertensive individuals. Many hypertensive Koreans
      do not comply with lifestyle recommendations for the management of hypertension.
      The association between the use of antihypertensive medications and non-adherence
      suggested an over-reliance on medication rather than a commitment to a healthy
      lifestyle. Our study highlights that efforts encouraging healthy lifestyles, as
      the first step in hypertension management, need to be increased. 

PMID- 26317339
TI  - Money Walks: Implicit Mobility Behavior and Financial Well-Being.
AB  - Traditional financial decision systems (e.g. credit) had to rely on explicit
      individual traits like age, gender, job type, and marital status, while being
      oblivious to spatio-temporal mobility or the habits of the individual involved.
      Emerging trends in geo-aware and mobile payment systems, and the resulting "big
      data," present an opportunity to study human consumption patterns across space
      and time. Taking inspiration from animal behavior studies that have reported
      significant interconnections between animal spatio-temporal "foraging" behavior
      and their life outcomes, we analyzed a corpus of hundreds of thousands of human
      economic transactions and found that financial outcomes for individuals are
      intricately linked with their spatio-temporal traits like exploration,
      engagement, and elasticity. Such features yield models that are 30% to 49% better
      at predicting future financial difficulties than the comparable demographic
      models. 

PMID- 26317338
TI  - Identifying a Neuromedin U Receptor 2 Splice Variant and Determining Its Roles in
      the Regulation of Signaling and Tumorigenesis In Vitro.
AB  - Neuromedin U (NMU) activates two G protein-coupled receptors, NMUR1 and NMUR2;
      this signaling not only controls many physiological responses but also promotes
      tumorigenesis in diverse tissues. We recently identified a novel truncated NMUR2
      derived by alternative splicing, namely NMUR2S, from human ovarian cancer cDNA.
      Sequence analysis, cell surface ELISA and immunocytochemical staining using 293T
      cells indicated that NMUR2S can be expressed well on the cell surface as a six
      transmembrane protein. Receptor pull-down and fluorescent resonance energy
      transfer assays demonstrated that NMUR1, NMUR2 and this newly discovered NMUR2S
      can not only form homomeric complexes but also heteromeric complexes with each
      other. Although not activated by NMU itself, functional assay in combination with
      receptor quantification and radio-ligand binding in 293T cells indicated that
      NMUR2S does not alter the translocation and stability of NMUR1 or NMUR2, but
      rather effectively dampens their signaling by blocking their NMU binding
      capability through receptor heterodimerization. We further demonstrated that NMU
      signaling is significantly up-regulated in human ovarian cancers, whereas
      expression of NMUR2S can block endogenous NMU signaling and further lead to
      suppression of proliferation in SKOV-3 ovarian cancer cells. In contrast, in
      monocytic THP-1 cells that express comparable levels of NMUR1 and NMUR2S,
      depletion of NMUR2S restored both the signaling and effect of NMU. Thus, these
      results not only reveal the presence of previously uncharacterized heteromeric
      relationships among NMU receptors but also provide NMUR2S as a potential
      therapeutic target for the future treatment of NMU signaling-mediated cancers. 

PMID- 26317337
TI  - Mitochondrial Activity and Cyr1 Are Key Regulators of Ras1 Activation of C.
      albicans Virulence Pathways.
AB  - Candida albicans is both a major fungal pathogen and a member of the commensal
      human microflora. The morphological switch from yeast to hyphal growth is
      associated with disease and many environmental factors are known to influence the
      yeast-to-hyphae switch. The Ras1-Cyr1-PKA pathway is a major regulator of C.
      albicans morphogenesis as well as biofilm formation and white-opaque switching.
      Previous studies have shown that hyphal growth is strongly repressed by
      mitochondrial inhibitors. Here, we show that mitochondrial inhibitors strongly
      decreased Ras1 GTP-binding and activity in C. albicans and similar effects were
      observed in other Candida species. Consistent with there being a connection
      between respiratory activity and GTP-Ras1 binding, mutants lacking complex I or
      complex IV grew as yeast in hypha-inducing conditions, had lower levels of GTP
      Ras1, and Ras1 GTP-binding was unaffected by respiratory inhibitors. Mitochondria
      perturbing agents decreased intracellular ATP concentrations and metabolomics
      analyses of cells grown with different respiratory inhibitors found consistent
      perturbation of pyruvate metabolism and the TCA cycle, changes in redox state,
      increased catabolism of lipids, and decreased sterol content which suggested
      increased AMP kinase activity. Biochemical and genetic experiments provide strong
      evidence for a model in which the activation of Ras1 is controlled by ATP levels
      in an AMP kinase independent manner. The Ras1 GTPase activating protein, Ira2,
      but not the Ras1 guanine nucleotide exchange factor, Cdc25, was required for the
      reduction of Ras1-GTP in response to inhibitor-mediated reduction of ATP levels.
      Furthermore, Cyr1, a well-characterized Ras1 effector, participated in the
      control of Ras1-GTP binding in response to decreased mitochondrial activity
      suggesting a revised model for Ras1 and Cyr1 signaling in which Cyr1 and Ras1
      influence each other and, together with Ira2, seem to form a master-regulatory
      complex necessary to integrate different environmental and intracellular signals,
      including metabolic status, to decide the fate of cellular morphology. 

PMID- 26317340
TI  - A Biochemical Approach to Understand the Pathogenesis of Advanced Pulmonary
      Arterial Hypertension: Metabolomic Profiles of Arginine, Sphingosine-1-Phosphate,
      and Heme of Human Lung.
AB  - Pulmonary arterial hypertension (PAH) is a vascular disease characterized by
      persistent precapillary pulmonary hypertension (PH), leading to progressive right
      heart failure and premature death. The pathological mechanisms underlying this
      condition remain elusive. Analysis of global metabolomics from lung tissue of
      patients with PAH (n = 8) and control lung tissue (n = 8) leads to a better
      understanding of disease progression. Using a combination of high-throughput
      liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased
      metabolomic profiles of disrupted arginine pathways with increased Nitric oxide
      (NO) and decreased arginine. Our results also showed specific metabolic pathways
      and genetic profiles with increased Sphingosine-1-phosphate (S1P) metabolites as
      well as increased Heme metabolites with altered oxidative pathways in the
      advanced stage of the human PAH lung. The results suggest that PAH has specific
      metabolic pathways contributing to the vascular remodeling in severe pulmonary
      hypertension. Profiling metabolomic alterations of the PAH lung has provided a
      new understanding of the pathogenic mechanisms of PAH, which benefits therapeutic
      targeting to specific metabolic pathways involved in the progression of PAH. 

PMID- 26317341
TI  - Fuel Use and Greenhouse Gas Emissions from Offshore Fisheries of the Republic of
      Korea.
AB  - Greenhouse Gas (GHG) emissions from the offshore fisheries industry in the
      Republic of Korea (Korea) were examined in response to growing concerns about
      global warming and the contribution of emissions from different industrial
      sectors. Fuel usage and GHG emissions (CO2, CH4, N2O) were analysed using the
      'Tier 1' method provided by the Intergovernmental Panel on Climate Change (IPCC)
      from the offshore fishery, which is the primary domestic seafood production
      sector in Korea. In 2013, fuel usage in the offshore fishery accounted for 59.7%
      (557,463 KL) of total fuel consumption of fishing vessels in Korea. Fuel
      consumption and thus GHG emissions were not stable through time in this industry,
      increasing by 2.4% p.a. for three consecutive years, from 2011 to 2013, despite a
      decrease in the number of vessels operating. GHG emissions generated in offshore
      fisheries also changed through time and increased from 1,442,975 tCO2e/year in
      2011 to 1,477,279 tCO2e/year in 2013. Changes in both fuel use and GHG emissions
      per kg offshore fish production appeared to be associated with decreasing catch
      rates by the fleet, which in turn were a reflection of decrease in fish biomass.
      Another important feature of GHG emissions in this industry was the high
      variation in GHG emission per kg fish product among different fishing methods.
      The long line fishery had approximately three times the emissions of the average
      production while the jigging fishery was more than two times higher than the
      average. Lowest emissions were from the trawl sector, which is regarded as having
      greatest environmental impact using traditional biodiversity metrics although had
      lowest environmental impact in terms of fuel and GHG emission metrics used in
      this study. The observed deterioration in fuel efficiency of the offshore fishery
      each year is of concern but also demonstrates that fuel efficiency can change,
      which shows there is opportunity to improve efficiency with changes to fishery
      management and harvesting operations. 

PMID- 26317342
TI  - Association of Nitric Oxide Synthase and Matrix Metalloprotease Single Nucleotide
      Polymorphisms with Preeclampsia and Its Complications.
AB  - BACKGROUND: Preeclampsia is one of the leading causes of maternal and neonatal
      morbidity and mortality in the world, but its appearance is still unpredictable
      and its pathophysiology has not been entirely elucidated. Genetic studies have
      associated single nucleotide polymorphisms in genes encoding nitric oxide
      synthase and matrix metalloproteases with preeclampsia, but the results are
      largely inconclusive across different populations. OBJECTIVES: To investigate the
      association of single nucleotide polymorphisms (SNPs) in NOS3 (G894T, T-786C, and
      a variable number of tandem repetitions VNTR in intron 4), MMP2 (C-1306T), and
      MMP9 (C-1562T) genes with preeclampsia in patients from Southeastern Brazil.
      METHODS: This prospective case-control study enrolled 77 women with preeclampsia
      and 266 control pregnant women. Clinical data were collected to assess risk
      factors and the presence of severe complications, such as eclampsia and HELLP
      (hemolysis, elevated liver enzymes, and low platelets) syndrome. RESULTS: We
      found a significant association between the single nucleotide polymorphism NOS3 T
      786C and preeclampsia, independently from age, height, weight, or the other SNPs
      studied, and no association was found with the other polymorphisms. Age and
      history of preeclampsia were also identified as risk factors. The presence of at
      least one polymorphic allele for NOS3 T-786C was also associated with the
      occurrence of eclampsia or HELLP syndrome among preeclamptic women. CONCLUSIONS:
      Our data support that the NOS3 T-786C SNP is associated with preeclampsia and the
      severity of its complications.

PMID- 26317343
TI  - Individual Spawning Duration of Captive Atlantic Bluefin Tuna (Thunnus thynnus)
      Revealed by Mitochondrial DNA Analysis of Eggs.
AB  - This study presents the first results on Atlantic bluefin tuna (Thunnus thynnus)
      individual spawning duration and its short-term temporal behavior. The study was
      based on direct measurements resulting from mtDNA analysis of the offspring of
      spawners held in transport cages during the 2013 spawning monitoring survey in
      Balearic waters. The number of females consisted of approximately 259 individuals
      with an average weight of 186 kg. The survey began on May 22 and ended on July 3.
      Spawning started on May 30 and was observed every night afterwards. The sampling
      of eggs for genetic monitoring was conducted for 9 days interspersed from the
      beginning of spawning to the end of the survey. A total of 946 eggs were analyzed
      and revealed 129 different haplotypes; 77 of these were not previously detected
      in the Mediterranean. A total of 69 haplotypes were observed in more than one
      spawning event and those with higher frequency lasted their maximum possible
      duration. The haplotypes present at the beginning of spawning were also
      identified at the end of the sampling, indicating a minimum spawning duration of
      34 days, and individual annual fecundity was estimated at around 1290 eggs gr(
      1). These results differed from those generally presumed until now and are
      indicative of a much higher fecundity. Females exhibited a regular spawning
      schedule but with the capacity to shift the spawning hour during the spawning
      season. These results were observed for the eastern population of Atlantic
      bluefin tuna and before extrapolating to the western population, their validity
      should be proved.

PMID- 26317344
TI  - Calcium Chloride in Neonatal Parenteral Nutrition Solutions with and without
      Added Cysteine: Compatibility Studies Using Laser and Micro-Flow Imaging
      Methodology.
AB  - BACKGROUND: Previous studies of compatibility of calcium chloride (CaCl2) and
      phosphates have not included particle counts in the range specified by the United
      States Pharmacopeia. Micro-flow imaging techniques have been shown to be
      comparable to light obscuration when determining particle count and size in
      pharmaceutical solutions. OBJECTIVE: The purpose of this study was to do
      compatibility testing for parenteral nutrition (PN) solutions containing CaCl2
      using dynamic light scattering and micro-flow imaging techniques. METHODS:
      Solutions containing TrophAmine (Braun Medical Inc, Irvine, CA), CaCl2, and
      sodium phosphate (NaPhos) were compounded with and without cysteine. All
      solutions contained standard additives to neonatal PN solutions including
      dextrose, trace metals, and electrolytes. Control solutions contained no calcium
      or phosphate. Solutions were analyzed for particle size and particle count. Means
      of Z-average particle size and particle counts of controls were determined. Study
      solutions were compared to controls and United States Pharmacopeia (USP) Chapter
      788 guidelines. The maximum amount of Phos that was compatible in solutions that
      contained at least 10 mmol/L of Ca in 2.5% amino acids (AA) was determined.
      Compatibility of these solutions was verified by performing analyses of 5 repeats
      of these solutions. Microscopic analyses of the repeats were also performed.
      RESULTS: Amounts of CaCl2 and NaPhos that were compatible in solutions containing
      1.5%, 2%, 2.5%, and 3% AA were determined. The maximum amount of NaPhos that
      could be added to TrophAmine solutions of > = 2.5% AA containing at least 10
      mmol/L of CaCl2 was 7.5 mmol/L. Adding 50 mg/dL of cysteine increased the amount
      of NaPhos that could be added to solutions containing 10 mmol/L of CaCl2 to 10
      mmol/L. CONCLUSION: Calcium chloride can be added to neonatal PN solutions
      containing NaPhos in concentrations that can potentially provide an intravenous
      intake of adequate amounts of calcium and phosphorus.

PMID- 26317345
TI  - TLR4 Expression by Liver Resident Cells Mediates the Development of Glucose
      Intolerance and Insulin Resistance in Experimental Periodontitis.
AB  - BACKGROUND: Results from epidemiological studies indicate a close association
      between periodontitis and type 2 diabetes mellitus. However, the mechanism
      linking periodontitis to glucose intolerance (GI) and insulin resistance (IR) is
      unknown. We therefore tested the hypothesis that periodontitis induces the
      development of GI/IR through a liver Toll-like receptor 4 (TLR4) dependent
      mechanism. METHODS: TLR4 chimeric mice were developed by bone marrow
      transplantation using green fluorescent protein expressing TLR4WT mouse (GFPWT)
      as donor and TLR4 WT or TLR4-/- as recipient mice (GFPWT:WT and GFPWT:KO chimeras
      respectively). These chimeras were subjected to experimental chronic
      periodontitis induced by repeated applications of LPS to the gingival sulci for
      18 weeks. The levels of GI/IR were monitored and plasma cytokines and LPS were
      determined at 18 weeks when differences in glucose tolerance were most apparent.
      Cytokine gene expression was measured in liver tissue by qPCR. RESULTS: Alveolar
      bone loss was significantly greater in GFPWT:WT chimeras treated with LPS
      compared with chimeras treated with PBS or GFPWT:KO chimeras. However, the degree
      of gingival inflammation was similar between GFPWT:WT and GFPWT:KO mice with LPS
      application. Severe GI/IR occurred in GFPWT:WT chimeras but not in the GFPWT:KO
      chimeras that were subjected to 18 weeks of LPS. Serum LPS was detected only in
      animals to which LPS was applied and the level was similar in GFPWT:WT and
      GFPWT:KO mice at the 18 week time point. Surprisingly, there was no significant
      difference in the plasma levels of IL1beta, IL6 and TNFalpha at 18 weeks in spite
      of the severe GI/IR in the GFPWT:WT chimeras with LPS application. Also, no
      difference in the expression of TNFalpha or IL6 mRNA was detected in the liver of
      GFPWT:WT vs GFPWT:KO mice. In contrast, liver IL1beta expression was
      significantly greater in GFPWT:WT chimeras compared to GFPWT:KO chimeras treated
      with LPS. CONCLUSION: We observed that GFPWT:WT, but not GFPWT:KO chimeras,
      treated with LPS developed GI/IR despite similar degrees of gingival
      inflammation, circulating cytokine levels, and LPS concentrations. We conclude
      that LPS from periodontitis sites has a pivotal role in triggering the
      development of GI/IR through a mechanism that involves TLR4 expression by
      resident macrophages/Kupffer cells in the liver.

PMID- 26317346
TI  - Preliminary Study of MR Diffusion Tensor Imaging of the Liver for the Diagnosis
      of Hepatocellular Carcinoma.
AB  - OBJECTIVES: To evaluate the feasibility of differentiating between hepatocellular
      carcinomas (HCC) and healthy liver using diffusion tensor imaging (DTI). MATERIAL
      AND METHODS: All subjects underwent an abdominal examination on a 3.0T MRI
      scanner. Two radiologists independently scored the image quality (IQ). An optimal
      set of DTI parameters was obtained from a group of fifteen volunteers with
      multiple b-values (100, 300, 500, and 800 s/mm2) and various diffusion-encoding
      directions (NED = 6, 9, and 12)using two way ANOVA analysis. Eighteen Patients
      with HCC underwent DTI scans with the optimized parameters. Fractional
      anisotropy(FA) and average apparent diffusion coefficient (ADC) values were
      measured. The differences of FA and ADC values between liver healthy region and
      HCC lesion were compared through paired t tests. RESULTS: There were no
      significant changes in liver IQ and FA/ADC values with increased NED(P >0.05),
      whereas the liver IQ and FA/ADC values decreased significantly with increased b
      values(P <0.05). Good IQ, acceptable scan time and reasonable FA/ADC values were
      acquired using NED = 9 with b-value of (0,300) s/mm2. Using the optimized DTI
      sequence, ADC value of the tumor lesion was significantly lower than that of the
      healthy liver region (1.30 +/- 0.34*10-3 vs 1.52 +/- 0.27*10-3 mm2/s, P = 0.013),
      whereas the mean FA value of the tumor lesion (0.42 +/- 0.11) was significantly
      higher than the normal liver region (0.32 +/- 0.10) (P = 0.004). CONCLUSION:
      Either FA or ADC value from DTI can be used to differentiate HCC from healthy
      liver. HCC lead to higher FA value and lower ADC value on DTI than healthy liver.

PMID- 26317347
TI  - Suppressive Role of PPARgamma-Regulated Endothelial Nitric Oxide Synthase in
      Adipocyte Lipolysis.
AB  - INTRODUCTION: Metabolic syndrome causes insulin resistance and is associated with
      risk factor clustering, thereby increasing the risk of atherosclerosis. Recently,
      endothelial nitric oxide synthase deficient (eNOS-/-) mice have been reported to
      show metabolic disorders. Interestingly, eNOS has also been reported to be
      expressed in non-endothelial cells including adipocytes, but the functions of
      eNOS in adipocytes remain unclear. METHODS AND RESULTS: The eNOS expression was
      induced with adipocyte differentiation and inhibition of eNOS/NO enhanced
      lipolysis in vitro and in vivo. Furthermore, the administration of a high fat
      diet (HFD) was able to induce non-alcoholic steatohepatitis (NASH) in eNOS-/-
      mice but not in wild type mice. A PPARgamma antagonist increased eNOS expression
      in adipocytes and suppressed HFD-induced fatty liver changes. CONCLUSIONS: eNOS-/
      mice induce NASH development, and these findings provide new insights into the
      therapeutic approach for fatty liver disease and related disorders.

PMID- 26317349
TI  - Predicting Greater Prairie-Chicken Lek Site Suitability to Inform Conservation
      Actions.
AB  - The demands of a growing human population dictates that expansion of energy
      infrastructure, roads, and other development frequently takes place in native
      rangelands. Particularly, transmission lines and roads commonly divide rural
      landscapes and increase fragmentation. This has direct and indirect consequences
      on native wildlife that can be mitigated through thoughtful planning and
      proactive approaches to identifying areas of high conservation priority. We used
      nine years (2003-2011) of Greater Prairie-Chicken (Tympanuchus cupido) lek
      locations totaling 870 unique leks sites in Kansas and seven geographic
      information system (GIS) layers describing land cover, topography, and
      anthropogenic structures to model habitat suitability across the state. The
      models obtained had low omission rates (<0.18) and high area under the curve
      scores (AUC >0.81), indicating high model performance and reliability of
      predicted habitat suitability for Greater Prairie-Chickens. We found that
      elevation was the most influential in predicting lek locations, contributing
      three times more predictive power than any other variable. However, models were
      improved by the addition of land cover and anthropogenic features (transmission
      lines, roads, and oil and gas structures). Overall, our analysis provides a
      hierarchal understanding of Greater Prairie-Chicken habitat suitability that is
      broadly based on geomorphological features followed by land cover suitability. We
      found that when land features and vegetation cover are suitable for Greater
      Prairie-Chickens, fragmentation by anthropogenic sources such as roadways and
      transmission lines are a concern. Therefore, it is our recommendation that future
      human development in Kansas avoid areas that our models identified as highly
      suitable for Greater Prairie-Chickens and focus development on land cover types
      that are of lower conservation concern. 

PMID- 26317348
TI  - Regulation of Mutagenic DNA Polymerase V Activation in Space and Time.
AB  - Spatial regulation is often encountered as a component of multi-tiered regulatory
      systems in eukaryotes, where processes are readily segregated by organelle
      boundaries. Well-characterized examples of spatial regulation are less common in
      bacteria. Low-fidelity DNA polymerase V (UmuD'2C) is produced in Escherichia coli
      as part of the bacterial SOS response to DNA damage. Due to the mutagenic
      potential of this enzyme, pol V activity is controlled by means of an elaborate
      regulatory system at transcriptional and posttranslational levels. Using single
      molecule fluorescence microscopy to visualize UmuC inside living cells in space
      and time, we now show that pol V is also subject to a novel form of spatial
      regulation. After an initial delay (~ 45 min) post UV irradiation, UmuC is
      synthesized, but is not immediately activated. Instead, it is sequestered at the
      inner cell membrane. The release of UmuC into the cytosol requires the RecA*
      nucleoprotein filament-mediated cleavage of UmuD->UmuD'. Classic SOS damage
      response mutants either block [umuD(K97A)] or constitutively stimulate
      [recA(E38K)] UmuC release from the membrane. Foci of mutagenically active pol V
      Mut (UmuD'2C-RecA-ATP) formed in the cytosol after UV irradiation do not co
      localize with pol III replisomes, suggesting a capacity to promote translesion
      DNA synthesis at lesions skipped over by DNA polymerase III. In effect, at least
      three molecular mechanisms limit the amount of time that pol V has to access DNA:
      (1) transcriptional and posttranslational regulation that initially keep the
      intracellular levels of pol V to a minimum; (2) spatial regulation via transient
      sequestration of UmuC at the membrane, which further delays pol V activation; and
      (3) the hydrolytic activity of a recently discovered pol V Mut ATPase function
      that limits active polymerase time on the chromosomal template. 

PMID- 26317350
TI  - A Novel Role for VICKZ Proteins in Maintaining Epithelial Integrity during
      Embryogenesis.
AB  - BACKGROUND: VICKZ (IGF2BP1,2,3/ZBP1/Vg1RBP/IMP1,2,3) proteins bind RNA and help
      regulate many RNA-mediated processes. In the midbrain region of early chick
      embryos, VICKZ is expressed in the neural folds and along the basal surface of
      the neural epithelium, but, upon neural tube closure, is down-regulated in
      prospective cranial neural crest (CNC) cells, concomitant with their emigration
      and epithelial-to-mesenchymal transition (EMT). Electroporation of constructs
      that modulate cVICKZ expression demonstrates that this down-regulation is both
      necessary and sufficient for CNC EMT. These results suggest that VICKZ down
      regulation in CNC cell-autonomously promotes EMT and migration. Reduction of
      VICKZ throughout the embryo, however, inhibits CNC migration non-cell
      autonomously, as judged by transplantation experiments in Xenopus embryos.
      RESULTS AND CONCLUSIONS: Given the positive role reported for VICKZ proteins in
      promoting cell migration of chick embryo fibroblasts and many types of cancer
      cells, we have begun to look for specific mRNAs that could mediate context
      specific differences. We report here that the laminin receptor, integrin alpha 6,
      is down-regulated in the dorsal neural tube when CNC cells emigrate, this process
      is mediated by cVICKZ, and integrin alpha 6 mRNA is found in VICKZ
      ribonucleoprotein complexes. Significantly, prolonged inhibition of cVICKZ in
      either the neural tube or the nascent dermomyotome sheet, which also dynamically
      expresses cVICKZ, induces disruption of these epithelia. These data point to a
      previously unreported role for VICKZ in maintaining epithelial integrity.

PMID- 26317351
TI  - Pharmacokinetics, Tissue Distribution, and Anti-Lipogenic/Adipogenic Effects of
      Allyl-Isothiocyanate Metabolites.
AB  - Allyl-isothiocyanate (AITC) is an organosulfur phytochemical found in abundance
      in common cruciferous vegetables such as mustard, wasabi, and cabbage. Although
      AITC is metabolized primarily through the mercapturic acid pathway, its exact
      pharmacokinetics remains undefined and the biological function of AITC
      metabolites is still largely unknown. In this study, we evaluated the inhibitory
      effects of AITC metabolites on lipid accumulation in vitro and elucidated the
      pharmacokinetics and tissue distribution of AITC metabolites in rats. We found
      that AITC metabolites generally conjugate with glutathione (GSH) or N
      acetylcysteine (NAC) and are distributed in most organs and tissues.
      Pharmacokinetic analysis showed a rapid uptake and complete metabolism of AITC
      following oral administration to rats. Although AITC has been reported to exhibit
      anti-tumor activity in bladder cancer, the potential bioactivity of its
      metabolites has not been explored. We found that GSH-AITC and NAC-AITC
      effectively inhibit adipogenic differentiation of 3T3-L1 preadipocytes and
      suppress expression of PPAR-gamma, C/EBPalpha, and FAS, which are up-regulated
      during adipogenesis. GSH-AITC and NAC-AITC also suppressed oleic acid-induced
      lipid accumulation and lipogenesis in hepatocytes. Our findings suggest that AITC
      is almost completely metabolized in the liver and rapidly excreted in urine
      through the mercapturic acid pathway following administration in rats. AITC
      metabolites may exert anti-obesity effects through suppression of adipogenesis or
      lipogenesis. 

PMID- 26317352
TI  - Molecular Analysis of Upper Tract and Bladder Urothelial Carcinoma: Results from
      a Microarray Comparison.
AB  - INTRODUCTION: Prior studies have shown genetic similarities between upper tract
      and bladder urothelial carcinoma. However, upper tract urothelial carcinoma tends
      to be higher grade than bladder urothelial carcinoma and tends to form in
      patients with certain familial conditions (e.g. Lynch Syndrome), indicating there
      may be unique biologic processes in these tumors. The purpose of this study was
      to evaluate the differences in gene expression between upper tract and bladder
      urothelial carcinoma using microarray data. DESIGN, SETTING, PARTICIPANTS: A
      search of publicly available microarray datasets identified a clinically
      annotated dataset of 12 upper tract and 20 bladder urothelial carcinoma
      specimens. Gene expression analysis of data derived from the Affymetrix
      HGU133Plus2 chip was performed. Bioconductor packages were used to evaluate
      clustering, differential gene expression, pathways relevant to oncology, and a
      basal/luminal signature in upper tract versus bladder urothelial carcinoma.
      RESULTS: When separated by pathologic T stage, there was evidence of differential
      clustering among pT3 tumors and significant gene expression differences in 81
      genes. Pathway analysis revealed differences in HGF and TNF signaling pathways.
      Upper tract tumors tended to have high expression of genes associated with a
      luminal subtype. One of the genes most highly expressed in upper tract tumors,
      SLITRK6, is the target of an antibody drug conjugate (AGS15E) currently in phase
      I clinical trials. CONCLUSIONS: This study provides evidence for molecular
      differences between upper tract and bladder urothelial carcinoma, some of which
      contribute to oncologic-relevant pathways. Upper tract tumors tended to express
      genes consistent with a luminal subtype. We also identify a marker, SLITRK6, as a
      potential target for patients with advanced upper tract urothelial carcinoma.

PMID- 26317353
TI  - Analysis of the Catecholaminergic Phenotype in Human SH-SY5Y and BE(2)-M17
      Neuroblastoma Cell Lines upon Differentiation.
AB  - Human cell lines are often used to investigate cellular pathways relevant for
      physiological or pathological processes or to evaluate cell toxicity or
      protection induced by different compounds, including potential drugs. In this
      study, we analyzed and compared the differentiating activities of three agents
      (retinoic acid, staurosporine and 12-O-tetradecanoylphorbol-13-acetate) on the
      human neuroblastoma SH-SY5Y and BE(2)-M17 cell lines; the first cell line is
      largely used in the field of neuroscience, while the second is still poorly
      characterized. After evaluating their effects in terms of cell proliferation and
      morphology, we investigated their catecholaminergic properties by assessing the
      expression profiles of the major genes involved in catecholamine synthesis and
      storage and the cellular concentrations of the neurotransmitters dopamine and
      noradrenaline. Our results demonstrate that the two cell lines possess similar
      abilities to differentiate and acquire a neuron-like morphology. The most evident
      effects in SH-SY5Y cells were observed in the presence of staurosporine, while in
      BE(2)-M17 cells, retinoic acid induced the strongest effects. Undifferentiated SH
      SY5Y and BE(2)-M17 cells are characterized by the production of both NA and DA,
      but their levels are considerably higher in BE(2)-M17 cells. Moreover, the
      NAergic phenotype appears to be more pronounced in SH-SY5Y cells, while BE(2)-M17
      cells have a more prominent DAergic phenotype. Finally, the catecholamine
      concentration strongly increases upon differentiation induced by staurosporine in
      both cell lines. In conclusion, in this work the catecholaminergic phenotype of
      the human BE(2)-M17 cell line upon differentiation was characterized for the
      first time. Our data suggest that SH-SY5Y and BE(2)-M17 represent two alternative
      cell models for the neuroscience field. 

PMID- 26317355
TI  - "Bicycles May Use Full Lane" Signage Communicates U.S. Roadway Rules and
      Increases Perception of Safety.
AB  - Many global challenges, including obesity, health care costs, and climate change,
      could be addressed in part by increasing the use of bicycles for transportation.
      Concern about the safety of bicycling on roadways is frequently cited as a
      deterrent to increasing bicycle use in the USA. The use of effective signage
      along roadways might help alleviate these concerns by increasing knowledge about
      the rights and duties of bicyclists and motorists, ideally reducing crashes. We
      administered a web-based survey, using Twitter for recruitment, to examine how
      well three US traffic control devices communicated the message that bicyclists
      are permitted in the center of the travel lane and do not have to "get out of the
      way" to allow motorists to pass without changing lanes: "Bicycles May Use Full
      Lane" and "Share the Road" signage, and Shared Lane Markings on the pavement.
      Each was compared to an unsigned roadway. We also asked respondents whether it
      was safe for a bicyclist to occupy the center of the travel lane. "Bicycles May
      Use Full Lane" signage was the most consistently comprehended device for
      communicating the message that bicyclists may occupy the travel lane and also
      increased perceptions of safety. "Share the Road" signage did not increase
      comprehension or perceptions of safety. Shared Lane Markings fell somewhere
      between. "Bicycles May Use Full Lane" signage showed notable increases in
      comprehension among novice bicyclists and private motor vehicle commuters,
      critical target audiences for efforts to promote bicycling in the USA. Although
      limited in scope, our survey results are indicative and suggest that Departments
      of Transportation consider replacing "Share the Road" with "Bicycles May Use Full
      Lane" signage, possibly combined with Shared Lane Markings, if the intent is to
      increase awareness of roadway rights and responsibilities. Further evaluation
      through virtual reality simulations and on-road experiments is merited. 

PMID- 26317354
TI  - Characterization of RNA from Exosomes and Other Extracellular Vesicles Isolated
      by a Novel Spin Column-Based Method.
AB  - Exosomes and other extracellular vesicles (commonly referred to as EVs) have
      generated a lot of attention for their potential applications in both diagnostics
      and therapeutics. The contents of these vesicles are the subject of intense
      research, and the relatively recent discovery of RNA inside EVs has raised
      interest in the biological function of these RNAs as well as their potential as
      biomarkers for cancer and other diseases. Traditional ultracentrifugation-based
      protocols to isolate EVs are labor-intensive and subject to significant
      variability. Various attempts to develop methods with robust, reproducible
      performance have not yet been completely successful. Here, we report the
      development and characterization of a spin column-based method for the isolation
      of total RNA from EVs in serum and plasma. This method isolates highly pure RNA
      of equal or higher quantity compared to ultracentrifugation, with high
      specificity for vesicular over non-vesicular RNA. The spin columns have a
      capacity to handle up to 4 mL sample volume, enabling detection of low-abundance
      transcripts in serum and plasma. We conclude that the method is an improvement
      over traditional methods in providing a faster, more standardized way to achieve
      reliable high quality RNA preparations from EVs in biofluids such as serum and
      plasma. The first kit utilizing this new method has recently been made available
      by Qiagen as "exoRNeasy Serum/Plasma Maxi Kit". 

PMID- 26317356
TI  - Acute Treatment with a Novel TRPC4/C5 Channel Inhibitor Produces Antidepressant
      and Anxiolytic-Like Effects in Mice.
AB  - Transient receptor potential canonical (TRPC) channels are widely expressed in
      brain and involved in various aspects of brain function. Both TRPC4 and TRPC5
      have been implicated in innate fear function, which represents a key response to
      environmental stress. However, to what extent the TRPC4/C5 channels are involved
      in psychiatric disorders remains unexplored. Here, we tested the antidepressant
      and anxiolytic-like effects of a newly identified TRPC4/C5 inhibitor, M084. We
      show that a single intraperitoneal administration of M084 at 10 mg/kg body weight
      to C57BL/6 male mice significantly shortened the immobility time in forced swim
      test and tail suspension test within as short as 2 hours. The M084-treated mice
      spent more time exploring in illuminated and open areas in light/dark transition
      test and elevated plus maze test. In mice subjected to chronic unpredictable
      stress, M084 treatment reversed the enhanced immobility time in forced swim test
      and decreased the latency to feed in novelty suppressed feeding test. The
      treatment of M084 increased BDNF expression in both mRNA and protein levels, as
      well as phosphorylation levels of AKT and ERK, in prefrontal cortex. Our results
      indicate that M084 exerts rapid antidepressant and anxiolytic-like effects at
      least in part by acting on BDNF and its downstream signaling. We propose M084 as
      a lead compound for further druggability research. 

PMID- 26317357
TI  - The Intraocular Pressure under Deep versus Moderate Neuromuscular Blockade during
      Low-Pressure Robot Assisted Laparoscopic Radical Prostatectomy in a Randomized
      Trial.
AB  - BACKGROUND: This study aimed to determine whether continuous deep neuromuscular
      blockade (NMB) improves the surgical conditions and facilitates robotic-assisted
      laparoscopic radical prostatectomy (RALRP) under low intra-abdominal pressure
      (IAP) to attenuate the increase in intraocular pressure (IOP) during CO2
      pneumoperitoneum in the steep Trendelenburg (ST) position. METHODS: Sixty-seven
      patients undergoing RALRP were randomly assigned to a moderate NMB group (Group
      M), including patients who received atracurium infusion until the end of the ST
      position, maintaining a train of four count of 1-2; and the deep NMB group (Group
      D), including patients who received rocuronium infusion, maintaining a post
      tetanic count of 1-2. IOP was measured in all patients at nine separate time
      points. All RALRPs were performed by one surgeon, who rated the overall and worst
      surgical conditions at the end of the ST position. RESULTS: The highest IOP value
      was observed at T4 (60 min after the ST position) in both Group M (23.3 +/- 2.7
      mmHg) and Group D (19.8 +/- 2.1 mmHg). RALRP was accomplished at an IAP of 8 mmHg
      in 88% Group D patients and 25% Group M patients. The overall surgical condition
      grade was 4.0 (3.0-5.0) in Group D and 3.0 (2.0-5.0) in Group M (P < 0.001).
      CONCLUSION: The current study demonstrated that continuous deep NMB may improve
      surgical conditions and facilitate RALRP at a low IAP, resulting in significant
      attenuation of the increase on IOP. Moreover, low-pressure pneumoperitoneum,
      facilitated by deep NMB still provided acceptable surgical conditions. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT02109133.

PMID- 26317358
TI  - Correction: Unconventional Gas and Oil Drilling Is Associated with Increased
      Hospital Utilization Rates.

PMID- 26317360
TI  - Analysis of Single Locus Trajectories for Extracting In Vivo Chromatin Tethering
      Interactions.
AB  - Is it possible to extract tethering forces applied on chromatin from the
      statistics of a single locus trajectories imaged in vivo? Chromatin fragments
      interact with many partners such as the nuclear membrane, other chromosomes or
      nuclear bodies, but the resulting forces cannot be directly measured in vivo.
      However, they impact chromatin dynamics and should be reflected in particular in
      the motion of a single locus. We present here a method based on polymer models
      and statistics of single trajectories to extract the force characteristics and in
      particular when they are generated by the gradient of a quadratic potential well.
      Using numerical simulations of a Rouse polymer and live cell imaging of the MAT
      locus located on the yeast Saccharomyces cerevisiae chromosome III, we recover
      the amplitude and the distance between the observed and the interacting monomer.
      To conclude, the confined trajectories we observed in vivo reflect local
      interaction on chromatin. 

PMID- 26317359
TI  - Proteins with Intrinsically Disordered Domains Are Preferentially Recruited to
      Polyglutamine Aggregates.
AB  - Intracellular protein aggregation is the hallmark of several neurodegenerative
      diseases. Aggregates formed by polyglutamine (polyQ)-expanded proteins, such as
      Huntingtin, adopt amyloid-like structures that are resistant to denaturation. We
      used a novel purification strategy to isolate aggregates formed by human
      Huntingtin N-terminal fragments with expanded polyQ tracts from both yeast and
      mammalian (PC-12) cells. Using mass spectrometry we identified the protein
      species that are trapped within these polyQ aggregates. We found that proteins
      with very long intrinsically-disordered (ID) domains (>= 100 amino acids) and RNA
      binding proteins were disproportionately recruited into aggregates. The removal
      of the ID domains from selected proteins was sufficient to eliminate their
      recruitment into polyQ aggregates. We also observed that several
      neurodegenerative disease-linked proteins were reproducibly trapped within the
      polyQ aggregates purified from mammalian cells. Many of these proteins have large
      ID domains and are found in neuronal inclusions in their respective diseases. Our
      study indicates that neurodegenerative disease-associated proteins are
      particularly vulnerable to recruitment into polyQ aggregates via their ID
      domains. Also, the high frequency of ID domains in RNA-binding proteins may
      explain why RNA-binding proteins are frequently found in pathological inclusions
      in various neurodegenerative diseases.

PMID- 26317362
TI  - Tooth Size Variation in Pinniped Dentitions.
AB  - It is contentious whether size variation among mammalian teeth is heterogeneous
      or homogeneous, whether the coefficient of variation is reliable, and whether the
      standard deviation of log-transformed data and the residual of standard deviation
      on mean variable size are useful replacements for the coefficient of variation.
      Most studies of tooth size variation have been on mammals with complex-crowned
      teeth, with relatively little attention paid to taxa with simple-crowned teeth,
      such as Pinnipedia. To fill this gap in knowledge and to resolve the existing
      controversies, we explored the variation of linear size variables (length and
      width) for all teeth from complete permanent dentitions of four pinniped species,
      two phocids (Histriophoca fasciata, Phoca largha) and two otariids (Callorhinus
      ursinus, Eumetopias jubatus). Size variation among these teeth was mostly
      heterogeneous both along the toothrow and among species. The incisors, canines,
      and mesial and distal postcanines were often relatively highly variable. The
      levels of overall dental size variation ranged from relatively low as in land
      carnivorans (Phoca largha and both otariids) to high (Histriophoca fasciata).
      Sexual size dimorphism varied among teeth and among species, with teeth being, on
      average, larger in males than in females. This dimorphism was more pronounced,
      and the canines were larger and more dimorphic relative to other teeth in the
      otariids than in the phocids. The coefficient of variation quantified variation
      reliably in most cases. The standard deviation of log-transformed data was
      redundant with the coefficient of variation. The residual of standard deviation
      on mean variable size was inaccurate when size variation was considerably
      heterogeneous among the compared variables, and was incomparable between species
      and between sexes. The existing hypotheses invoking developmental fields,
      occlusal complexity, and the relative timing of tooth formation and sexually
      dimorphic hormonal activity do not adequately explain the differential size
      variation along the pinniped toothrow. 

PMID- 26317361
TI  - Genome-Wide Study of Structural Variants in Bovine Holstein, Montbeliarde and
      Normande Dairy Breeds.
AB  - High-throughput sequencing technologies have offered in recent years new
      opportunities to study genome variations. These studies have mostly focused on
      single nucleotide polymorphisms, small insertions or deletions and on copy number
      variants. Other structural variants, such as large insertions or deletions,
      tandem duplications, translocations, and inversions are less well-studied,
      despite that some have an important impact on phenotypes. In the present study,
      we performed a large-scale survey of structural variants in cattle. We report the
      identification of 6,426 putative structural variants in cattle extracted from
      whole-genome sequence data of 62 bulls representing the three major French dairy
      breeds. These genomic variants affect DNA segments greater than 50 base pairs and
      correspond to deletions, inversions and tandem duplications. Out of these, we
      identified a total of 547 deletions and 410 tandem duplications which could
      potentially code for CNVs. Experimental validation was carried out on 331
      structural variants using a novel high-throughput genotyping method. Out of
      these, 255 structural variants (77%) generated good quality genotypes and 191
      (75%) of them were validated. Gene content analyses in structural variant regions
      revealed 941 large deletions removing completely one or several genes, including
      10 single-copy genes. In addition, some of the structural variants are located
      within quantitative trait loci for dairy traits. This study is a pan-genome
      assessment of genomic variations in cattle and may provide a new glimpse into the
      bovine genome architecture. Our results may also help to study the effects of
      structural variants on gene expression and consequently their effect on certain
      phenotypes of interest. 

PMID- 26317363
TI  - Suvorexant for Primary Insomnia: A Systematic Review and Meta-Analysis of
      Randomized Placebo-Controlled Trials.
AB  - OBJECTIVE: We performed a systematic review and meta-analysis of double-blind,
      randomized, placebo-controlled trials evaluating suvorexant for primary insomnia.
      METHODS: Relevant studies were identified through searches of PubMed, databases
      of the Cochrane Library, and PsycINFO citations through June 27, 2015. We
      performed a systematic review and meta-analysis of suvorexant trial efficacy and
      safety outcomes. The primary efficacy outcomes were either subjective total sleep
      time (sTST) or subjective time-to-sleep onset (sTSO) at 1 month. The secondary
      outcomes were other efficacy outcomes, discontinuation rate, and individual
      adverse events. The risk ratio, number-needed-to-treat/harm, and weighted mean
      difference (WMD) and 95% confidence intervals (CI) based on a random effects
      model were calculated. RESULTS: The computerized literature database search
      initially yielded 48 results, from which 37 articles were excluded following a
      review of titles and abstracts and another eight review articles after full-text
      review. Thus, we identified 4 trials that included a total of 3,076 patients.
      Suvorexant was superior to placebo with regard to the two primary efficacy
      outcomes (sTST: WMD = -20.16, 95% CI = -25.01 to -15.30, 1889 patients, 3 trials,
      sTSO: WMD = -7.62, 95% CI = -11.03 to -4.21, 1889 patients, 3 trials) and was not
      different from placebo in trial discontinuations. Suvorexant caused a higher
      incidence than placebo of at least one side effects, abnormal dreams, somnolence,
      excessive daytime sleepiness/sedation, fatigue, dry mouth, and rebound insomnia.
      CONCLUSIONS: Our analysis of published trial results suggests that suvorexant is
      effective in treating primary insomnia and is well-tolerated.

PMID- 26317364
TI  - The Effect of Long-Term Continuous Cropping of Black Pepper on Soil Bacterial
      Communities as Determined by 454 Pyrosequencing.
AB  - In the present study, 3 replanted black pepper orchards with continuously
      cropping histories for 10, 21, and 55 years in tropical China, were selected for
      investigating the effect of monoculture on soil physiochemical properties, enzyme
      activities, bacterial abundance, and bacterial community structures. Results
      showed long-term continuous cropping led to a significant decline in soil pH,
      organic matter contents, enzymatic activities, and resulted in a decrease in soil
      bacterial abundance. 454 pyrosequencing analysis of 16S rRNA genes revealed that
      the Acidobacteria and Proteobacteria were the main phyla in the replanted black
      pepper orchard soils, comprising up to 73.82% of the total sequences; the
      relative abundances of Bacteroidetes and Firmicutes phyla decreased with long
      term continuous cropping; and at genus level, the Pseudomonas abundance
      significantly depleted after 21 years continuous cropping. In addition, bacterial
      diversity significantly decreased after 55 years black pepper continuous
      cropping; obvious variations for community structures across the 3 time-scale
      replanted black pepper orchards were observed, suggesting monoculture duration
      was the major determinant for bacterial community structure. Overall, continuous
      cropping during black pepper cultivation led to a significant decline in soil pH,
      organic matter contents, enzymatic activities, resulted a decrease in soil
      bacterial abundance, and altered soil microbial community membership and
      structure, which in turn resulted in black pepper poor growth in the continuous
      cropping system. 

PMID- 26317366
TI  - High Pressure-Temperature Phase Diagram of 1,1-Diamino-2,2-dinitroethylene (FOX
      7).
AB  - The pressure-temperature (P-T) phase diagram of 1,1-diamino-2,2-dinitroethylene
      (FOX-7) was determined by in situ synchrotron infrared radiation spectroscopy
      with the resistively heated diamond anvil cell (DAC) technique. The stability of
      high-P-T FOX-7 polymorphs is established from ambient pressure up to 10 GPa and
      temperatures until decomposition. The phase diagram indicates two near isobaric
      phase boundaries at ~2 GPa (alpha -> I) and ~5 GPa (I -> II) that persists from
      25  degrees C until the onset of decomposition at ~300  degrees C. In addition,
      the ambient pressure, high-temperature alpha -> beta phase transition (~111 
      degrees C) lies along a steep boundary (~100  degrees C/GPa) with a alpha-beta
      delta triple point at ~1 GPa and 300  degrees C. A 0.9 GPa isobaric temperature
      ramping measurement indicates a limited stability range for the gamma-phase
      between 0.5 and 0.9 GPa and 180 and 260  degrees C, terminating in a beta-gamma
      delta triple point. With increasing pressure, the delta-phase exhibited a small
      negative dT/dP slope (up to ~0.2 GPa) before turning over to a positive 70 
      degrees C/GPa slope, at higher pressures. The decomposition boundary (~55 
      degrees C/GPa) was identified through the emergence of spectroscopic signatures
      of the characteristic decomposition products as well as trapped inclusions within
      the solid KBr pressure media. 

PMID- 26317365
TI  - The Relationship between Parental Behaviors and Children's Sugary Drink
      Consumption Is Moderated by a Television in the Child's Bedroom.
AB  - BACKGROUND: The aim of this longitudinal study was to examine the link between
      perceived authoritative parenting behaviors and sugary drink consumption among
      children from low-income families who do or do not have televisions (TVs) in
      their bedrooms. METHODS: Middle school students (N = 480) completed a baseline
      survey in sixth grade and a follow-up survey in seventh grade. The students were
      recruited from 12 schools in a low-income, predominantly black (33%) and Latino
      (48%), urban school district. The survey assessed the children's perception of
      their parents' controlling and nurturing behaviors, the presence of a TV in their
      bedrooms, and their level of sugary drink consumption on the previous school day.
      Children's report of specific controlling and nurturing parental behaviors were
      used to create an "authoritative parenting" score. Regression analyses were used
      to test the main and interactive effects of authoritative parenting behaviors and
      having a TV in the bedroom with sugary drink consumption in seventh grade,
      controlling for age, race/ethnicity, gender, BMI, and sugary drink consumption in
      sixth grade. RESULTS: A significant interaction emerged: The authoritative
      parenting score predicted lower levels of sugary drink consumption in seventh
      grade, but this relationship was moderated by whether or not there was a TV in
      the child's bedroom. CONCLUSION: A TV in the child's bedroom may weaken the
      positive influence of authoritative parenting behaviors on limiting sugary drink
      consumption among middle school children from low-income families. Stronger
      initiatives are recommended to educate parents and help them refrain from placing
      TVs in their children's bedrooms.

PMID- 26317367
TI  - How does the 'rest-self overlap' mediate the qualitative and automatic features
      of self-reference?
AB  - The target article points out the qualitative and automatic features of self
      reference while leaving open the underlying neural mechanisms. Based on empirical
      evidence about rest-self overlap and rest-stimulus interaction being special for
      self-related stimuli, I postulate that the resting state shows self-specific
      organization. The resting state's self-specific organization may be encoded by
      activity balances between different networks which in turn predispose the
      qualitative features of subsequent self-related stimulus-induced activity in, for
      instance, SAN as well as the automatic features of self-reference effects. 

PMID- 26317368
TI  - How sex work becomes an option: Experiences of female sex workers in Kerman,
      Iran.
AB  - Sex work is rarely an occupation of choice for Iranian women and is often
      described as a last resort. While several factors play a role in creating an
      environment where individuals become involved in sex work, female sex workers'
      experiences regarding entry into sex work in Iran are poorly understood. In this
      qualitative study, a convenience sample of 24 participants was recruited from a
      drop-in centre for vulnerable women in Kerman, Iran. Through in-depth interviews,
      participants were asked about their personal lived experiences of initiating sex
      work. Grounded theory was used to analyse findings from this research. We learned
      that major factors impacting on women's initiation into sex work circulated
      around their vulnerability and chronic poverty. Participants continued to sell
      sex due to their limited opportunities, drug dependence and financial needs.
      Improving sex workers' economic status could be a vital intervention in providing
      vulnerable women with options other than sex work. Female sex workers should be
      provided with government support and educational programmes delivered through
      special centres. Despite the illegal status of their work, sex workers' needs
      should be recognised across all aspects of policy and legislation. 

PMID- 26317369
TI  - Malaria Parasite Survival Depends on Conserved Binding Peptides' Critical
      Biological Functions.
AB  - Biochemical, structural and single amino acid level analysis of 49 Plasmodium
      falciparum protein regions (13 sporozoite and 36 merozoite proteins) has
      highlighted the functional role of each conserved high activity binding peptide
      (cHABP) in cell host-microbe interaction, involving biological functions such as
      gliding motility, traversal activity, binding invasion, reproduction, nutrient
      ion transport and the development of severe malaria. Each protein's key function
      in the malaria parasite's asexual lifecycle (pre-erythrocyte and erythro-cyte) is
      described in terms of cHABPs; their sequences were located in elegant work
      published by other groups regarding critical binding regions implicated in
      malarial parasite invasion. Such cHABPs represent the starting point for
      developing a logical and rational methodology for selecting an appropriate
      mixture of modified cHABPs to be used in a completely effective, synthetic
      antimalarial vaccine. Such methodology could be used for developing vaccines
      against diseases scourging humanity.

PMID- 26317370
TI  - Predicting Gay Affirmative Practice from the Theory of Planned Behavior.
AB  - This study utilized the theory of planned behavior to examine individual
      intentions to engage in gay affirmative practice among aging-focused
      professionals (N = 83) in the Midwestern United States. Participants completed
      self-report measures of perceived agency norms and individual attitudes related
      to the treatment of gay men and lesbians, intentions to provide gay affirmative
      care, and perceived behavioral control. Attitudes, norms and perceived behavioral
      control were examined as predictors of intentions; attitudes of individual aging
      service professionals emerged as the strongest predictor. Results indicated that
      affirmative attitudes within the agency may be important in predicting intentions
      to provide this type of care.

PMID- 26317371
TI  - Development-linked changes in DNA methylation and hydroxymethylation in humans:
      interview with Dr Melanie Ehrlich.

PMID- 26317372
TI  - Effect of Early Individualized Dietary Counseling on Weight Loss, Complications,
      and Length of Hospital Stay in Patients With Head and Neck Cancer: A Comparative
      Study.
AB  - Patients with head and neck cancer (HNC) are at risk for undernutrition. Dietary
      counseling during treatment has positive effects on nutritional status and
      quality of life, however, the effects of dietary counseling started before
      initiation of treatment are currently unknown. Therefore we assessed the effect
      of early individualized dietary counseling (DC) on weight loss, major
      complications, and length of hospital stay (LOS) in patients with HNC. Ninety
      five newly diagnosed HNC patients with (risk of) undernutrition receiving DC were
      compared to 95 matched HNC patients receiving usual nutritional care (UC).
      Difference in weight change over time was analyzed by generalized estimating
      equations (GEE). Differences in complications and LOS were studied by Pearson chi
      squared and student's t-tests. Weight change between diagnosis and end of
      treatment was -6.0 +/- 6.9% (DC) and -5.4 +/- 5.7% (UC; GEE: -0.4kg, 95%
      confidence interval: -1.2 to 0.5; P = 0.44). Less DC patients experienced overall
      postoperative complications (44%/70%, P = 0.04). No effect on major postoperative
      or (chemo)radiotherapy complications or LOS was found. This study showed a lower
      prevalence of overall postoperative complications in HNC patients receiving DC
      but could not demonstrate an effect on weight loss, other complications, and LOS.

PMID- 26317373
TI  - Wetting Behavior in Colloid-Polymer Mixtures at Different Substrates.
AB  - We present experimental observations on wetting phenomena in depletion
      interaction driven, phase separated colloidal dispersions. The contact angle of
      the colloidal liquid-gas interface at a solid substrate was determined for a
      series of compositions. Upon approach to the critical point, a transition occurs
      from partial to complete wetting. The interaction with the substrate was
      manipulated by modifying the substrate with a polymer. In that case, a transition
      from partial to complete drying is observed upon approach to the critical point. 

PMID- 26317374
TI  - Endoscopic endonasal dacryocystorhinostomy with ostial stent intubation following
      nasolacrimal duct stent incarceration--reply.

PMID- 26317375
TI  - The Acute Effects of Nonstimulant Over-the-Counter Dietary Herbal Supplements on
      Resting Metabolic Rate.
AB  - BACKGROUND: Weight loss supplements are widely advertised and highly sought out
      products. Many supplements claim to increase body fat utilization, increase
      resting metabolic rate (RMR), and to improve body composition by decreasing total
      body fat composition. Therefore, the purpose of this study was to determine the
      acute effect of nonstimulant herbal supplements on RMR and substrate utilization.
      METHODS: Ten female and 16 male participants (mean age 23.7 +/- 3.9 years; mean
      weight 79.2 +/- 18.2 kg) completed a random-repeated measures crossover study.
      Participants completed a total of three RMRs by either ingesting a placebo (P) or
      one of two supplements [raspberry ketones (R) or metabolic activator blend (MAB)]
      2 hours prior to testing. RESULTS: No significant difference was found for RMR
      for P vs. MAB (p = .130), vs. R (p = .588), and MAB vs. R (p = .636). No
      significant difference was found for respiratory quotient for P vs. MAB (p =
      .056), vs. R (p = .149), and MAB vs. R (p = .764). No significant difference was
      found for substrate utilization: percent carbohydrate utilization, P vs. MAB (p =
      .052), P vs. R (p = .124), and MAB vs. R (p = .680); and percent fat utilization,
      P vs. MAB (p = .052), P vs. R (p = .120), and MAB vs. R (p = .749). CONCLUSIONS:
      Therefore, nonstimulant weight loss supplements may not be beneficial for weight
      loss, or an increase of fat utilization.

PMID- 26317376
TI  - Review of Telemicrobiology.
AB  - CONTEXT: Microbiology laboratories are continually pursuing means to improve
      quality, rapidity, and efficiency of specimen analysis in the face of limited
      resources. One means by which to achieve these improvements is through the remote
      analysis of digital images. Telemicrobiology enables the remote interpretation of
      images of microbiology specimens. To date, the practice of clinical
      telemicrobiology has not been thoroughly reviewed. OBJECTIVE: To identify the
      various methods that can be employed for telemicrobiology, including emerging
      technologies that may provide value to the clinical laboratory. DATA SOURCES:
      Peer-reviewed literature, conference proceedings, meeting presentations, and
      expert opinions pertaining to telemicrobiology have been evaluated. CONCLUSIONS:
      A number of modalities have been employed for telemicroscopy, including static
      capture techniques, whole slide imaging, video telemicroscopy, mobile devices,
      and hybrid systems. Telemicrobiology has been successfully implemented for
      several applications, including routine primary diagnosis, expert
      teleconsultation, and proficiency testing. Emerging areas of telemicrobiology
      include digital plate reading of bacterial cultures, mobile health applications,
      and computer-augmented analysis of digital images. To date, static image capture
      techniques have been the most widely used modality for telemicrobiology, despite
      newer technologies being available that may produce better quality
      interpretations. Telemicrobiology adds value, quality, and efficiency to the
      clinical microbiology laboratory, and increased adoption of telemicrobiology is
      anticipated.

PMID- 26317378
TI  - Impact of hours worked by a urologist prior to performing ureteroscopy on its
      safety and efficacy.
AB  - OBJECTIVE: The aim of this study was to evaluate the impact of hours worked by a
      urologist before performing ureteroscopy on its safety and efficacy. MATERIALS
      AND METHODS: Patients treated at a single institution from January 2010 to
      December 2013 were analyzed. The study assessed patient, stone and surgical
      parameters, stone-free rates and intraoperative complications performed in three
      work duration categories: less than 6 h, 6-12 h and more than 12 h of urologist's
      work. Statistical analyses included the chi-squared test, Kruskal-Wallis test,
      and univariate and multivariate logistic regression analyses. RESULTS: In total,
      469 ureteroscopies were analyzed. Intraoperative complications differed non
      significantly in the corresponding time categories: ureteral perforations (< 6 h
      4.4%, 6-12 h 3.2%, > 12 h 7%, p = 0.46) and avulsions (all 0%). Rates for
      complete stone removal were 82% within the first 12 h vs 70.2% after 12 h (p =
      0.03). Corresponding partial stone-free rates were 4.1% vs 3.5% (p = 0.83) and
      rates of unsuccessful ureteroscopy were 13.8% vs 26.3% (p = 0.01). In
      multivariate regression analysis, patients treated after 12 h of urologist's work
      had a 2.4 times higher risk of an unsuccessful ureteroscopy [odds ratio (OR) =
      2.4, 95% confidence interval (CI) 1.2-4.7, p = 0.001] and lower chances of
      complete stone removal (OR = 0.46, 95% CI 0.24-0.89, p = 0.02). The odds of
      ureteral perforations were similar (p = 0.28). CONCLUSION: Work duration before
      ureteroscopy did not affect its safety. Stone-free rates decreased with
      increasing working time. Working time exceeding 12 h was identified as an
      independent risk factor for impaired stone-free rates.

PMID- 26317379
TI  - Medical Cannabis in Arizona: Patient Characteristics, Perceptions, and
      Impressions of Medical Cannabis Legalization.
AB  - Many advances have been made toward understanding the benefits of medical
      cannabis. However, less is known about medical cannabis patients themselves.
      Prior research has uncovered many important patient characteristics, but most of
      that work has been conducted with participants in California, who may not
      represent medical cannabis patients throughout the United States. Furthermore, it
      is unknown if medical cannabis legalization, which typically imposes strict
      regulations on cannabis cultivation and sale, impacts patients' experiences
      acquiring and using cannabis. The goal of this study was to address these
      limitations by (1) examining the characteristics, perceptions, and behaviors of
      medical cannabis patients in Arizona; and (2) questioning participants with a
      history of cannabis use regarding their experiences with cannabis before and
      after legalization. Patients in Arizona share many characteristics with those in
      California, but also key differences, such as average age and degree of cannabis
      consumption. Participants also had positive perceptions of the effect of medical
      cannabis legalization, reporting that feelings of safety and awareness were
      higher after legalization compared to before. The results are discussed in
      relation to evidence from patients in other states and in terms of their
      potential policy implications. 

PMID- 26317377
TI  - The role of endocytic Rab GTPases in regulation of growth factor signaling and
      the migration and invasion of tumor cells.
AB  - Metastasis is characterized pathologically by uncontrolled cell invasion,
      proliferation, migration and angiogenesis. It is a multistep process that
      encompasses the modulation of membrane permeability and invasion, cell spreading,
      cell migration and proliferation of the extracellular matrix, increase in cell
      adhesion molecules and interaction, decrease in cell attachment and induced
      survival signals and propagation of nutrient supplies (blood vessels). In cancer,
      a solid tumor cannot expand and spread without a series of synchronized events.
      Changes in cell adhesion receptor molecules (e.g., integrins, cadherin-catenins)
      and protease expressions have been linked to tumor invasion and metastasis. It
      has also been determined that ligand-growth factor receptor interactions have
      been associated with cancer development and metastasis via the endocytic pathway.
      Specifically, growth factors, which include IGF-1 and IGF-2 therapy, have been
      associated with most if not all of the features of metastasis. In this review, we
      will revisit some of the key findings on perhaps one of the most important
      hallmarks of cancer metastasis: cell migration and cell invasion and the role of
      the endocytic pathway in mediating this phenomenon. 

PMID- 26317380
TI  - Flies do the locomotion.
AB  - Genetic techniques have shed new light on the organization of the neurons in the
      ventral nervous system of the fruit fly. 

PMID- 26317381
TI  - Zinc as a possible preventive and therapeutic agent in pancreatic, prostate, and
      breast cancer.
AB  - Zinc is a vital nutrient for human health. Over 300 biological functions in the
      human body rely on zinc. Even though zinc is incredibly important for our
      physiology and pathology, our current understanding of zinc, as it relates to
      tumor cell biology, leaves much to be desired. As with other natural,
      nonpatentable, and inexpensive agents, zinc remains a subject of explorative
      research for scientific interest rather than being promoted for practical use. To
      date, more than 5000 studies with the keywords 'zinc' and 'cancer' have been
      indexed in the Web of Knowledge portal. Although the numbers of papers have
      increased 2.5-fold during the last decade, these vast research data have not
      generated a single recommendation for the incorporation of zinc use in cancer
      prevention and treatment. In this review, we intend to analyze the current
      available research data and epidemiological and clinical evidence on the role of
      zinc in human cancer prevention and treatment. We focus on the cancers -
      prostate, breast, and pancreatic - for which the most basic and epidemiological
      studies with zinc have been carried out. The pancreas, and prostate and mammary
      glands are secretory tissues that have unusual zinc requirements; they tightly
      regulate zinc metabolism through integration of zinc import, sequestration, and
      export mechanisms. This suggests to us that zinc could play an important role in
      the physiology and pathology of these organs. The objective of this review was to
      stimulate more interest in the research field, focusing on the role of zinc as a
      possible preventive and therapeutic agent and the accelerated application of this
      inexpensive and easily accessible nutrient in clinical oncology.

PMID- 26317382
TI  - Ganoderma: insights into anticancer effects.
AB  - The genus Ganoderma includes about 80 species growing on cut or rotten trees. The
      most commonly used species is Ganoderma ludicum. Biomolecules responsible for the
      health benefits of Ganoderma are polysaccharides with an immunostimulative effect
      and triterpenes with a cytotoxic action. For more than 2000 years, it has been
      used traditionally in the treatment of various pathological conditions and
      recently, its immunoregulatory, antiviral, antibacterial, antioxidant,
      hepatoprotective, and anticancer potential has been confirmed. A wide range of
      Ganoderma extracts and preparations arrest the cell cycle in different phases and
      consequently inhibit the growth of various types of cancer cells. Extracts
      containing polysaccharides stimulate immunological reactions through the
      production of various cytokines and mobilization of immune system cells. In-vivo
      studies have confirmed the anticancer potential and the antimetastatic effects of
      compounds originating from Ganoderma. There is also evidence for the
      chemopreventive action of Ganoderma extracts in bladder, prostate, liver, and
      breast cancer. The results of clinical studies suggest the combined use of G.
      lucidum with conventional chemotherapy/radiotherapy, but the methodology and the
      results of these studies are being questioned. Therefore, a constant need for new
      clinical trials exists.

PMID- 26317383
TI  - Longitudinal association of hemostatic factors with risk for cancers of the
      breast, colorectum, and lung among postmenopausal women.
AB  - The aim of this study was to examine whether hemostatic factors associated with
      coagulation and inflammation pathways are associated with cancer risk in
      postmenopausal women. We used data from the Women's Health Initiative study to
      examine the association of plasma fibrinogen levels, factor VII antigen activity,
      and factor VII concentration measured at baseline and during follow-up with the
      risk for cancers of the breast, colorectum, and lung. Among 5287 women who were
      followed up for a median of 11.4 years, 275 cases of breast cancer, 102 cases of
      colorectal cancer, and 90 cases of lung cancer were identified. Cox proportional
      hazards models were used to estimate hazard ratios and 95% confidence intervals
      for the association of hemostatic factors with each cancer. Hemostatic factors
      were not associated with breast cancer in either baseline or longitudinal
      analyses. Baseline hemostatic factors showed weak associations with colorectal
      cancer; however, no association was seen in longitudinal analyses. Fibrinogen was
      positively associated with lung cancer in both baseline and longitudinal
      analyses; the association was seen only in never and former smokers, not in
      current smokers. We found no evidence of an association between hemostatic
      factors and breast or colorectal cancer in postmenopausal women. The positive
      association of fibrinogen levels with lung cancer requires confirmation in larger
      studies.

PMID- 26317384
TI  - Cancer incidence predictions in the North of Portugal: keeping population-based
      cancer registration up to date.
AB  - Decision making towards cancer prevention and control requires monitoring of
      trends in cancer incidence and accurate estimation of its burden in different
      settings. We aimed to estimate the number of incident cases in northern Portugal
      for 2015 and 2020 (all cancers except nonmelanoma skin and for the 15 most
      frequent tumours). Cancer cases diagnosed in 1994-2009 were collected by the
      North Region Cancer Registry of Portugal (RORENO) and corresponding population
      figures were obtained from Statistics Portugal. JoinPoint regression was used to
      analyse incidence trends. Population projections until 2020 were derived by
      RORENO. Predictions were performed using the Poisson regression models proposed
      by Dyba and Hakulinen. The number of incident cases is expected to increase by
      18.7% in 2015 and by 37.6% in 2020, with lower increments among men than among
      women. For most cancers considered, the number of cases will keep rising up to
      2020, although decreasing trends of age-standardized rates are expected for some
      tumours. Cervix was the only cancer with a decreasing number of incident cases in
      the entire period. Thyroid and lung cancers were among those with the steepest
      increases in the number of incident cases expected for 2020, especially among
      women. In 2020, the top five cancers are expected to account for 82 and 62% of
      all cases diagnosed in men and women, respectively. This study contributes to a
      broader understanding of cancer burden in the north of Portugal and provides the
      basis for keeping population-based incidence estimates up to date.

PMID- 26317385
TI  - Length but not transverse diameter of the excision specimen for high-grade
      cervical intraepithelial neoplasia (CIN 2-3) is a predictor of pregnancy outcome.
AB  - The objective of this study was to analyze the impact of cone characteristics
      (depth, transverse diameter, and volume) on subsequent pregnancies after the loop
      electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia
      (CIN 2-3). Pregnancy outcomes (preterm birth, gestational age at birth, mode of
      delivery, and birth weight) of 501 women with singleton gestations and no
      previous preterm birth or history of late miscarriage, who had previously
      undergone a single LEEP for CIN 2-3, were retrospectively analyzed with respect
      to length, transverse diameter, and volume of the excision specimen. The overall
      incidence of preterm birth was 2.4%. The rate of preterm birth in women with
      length greater than 20 mm or volume greater than 2.5 cm was significantly higher
      than that in women with length between 15 and 19 mm (15.6 vs. 3.9%, P=0.02) or
      women with volume between 2.0 and 2.4 cm (5.8 vs. 1.6%, P=0.04). A linear inverse
      correlation (r=-0.3, P<0.001) between gestational age at birth and length, but
      not volume (r=0.0, P=0.9) or transverse diameter (r=0.2, P<0.0001), emerged. The
      mode of delivery was not affected by cone characteristics. Length, but not
      transverse diameter and volume, of the excised specimen seems to be related to a
      lower gestational age at birth. When excisions are performed under strict
      colposcopic guidance, with a correct modulation of cone length, the risk for
      preterm birth and cesarean delivery in subsequent pregnancies is not increased.

PMID- 26317386
TI  - Assessment of epicardial adipose tissue thickness in patients with resistant
      hypertension.
AB  - OBJECTIVE: Recent studies have shown that epicardial adipose tissue (EAT)
      thickness is increased in patients with hypertension. In this study, we aimed to
      investigate the relation of EAT thickness with resistant hypertension (RHT).
      PARTICIPANTS AND METHODS: Study participants (n=150) were classified into three
      groups according to their office and ambulatory blood pressure measurements: RHT
      (n=50), controlled hypertension (CHT, n=50), and normotension (NT, n=50). All
      patients underwent a transthoracic echocardiographic examination to measure EAT
      thickness. RESULTS: Clinical and biochemical characteristics of the groups were
      similar, except the CRP level, which was significantly increased in hypertensive
      patients compared with patients with NT (P<0.001). EAT thickness differed
      significantly between groups (P<0.001). The highest values were obtained in the
      RHT group (4.64+/-1.24 cm), followed by the CHT (3.3+/-0.82 cm) and NT (2.6+/
      0.76 cm) groups. Multivariate analysis indicated age, physical activity level,
      and EAT thickness as independent predictors of RHT. The optimal cut-off value of
      EAT thickness for detection of RHT was found to be 3.42 cm, with a sensitivity
      and specificity of 82 and 77%, respectively (AUC=0.87, 95% confidence interval
      0.81-0.92, P<0.000). CONCLUSION: EAT can be effective on blood pressure by
      several mechanisms. In this study, for the first time in the literature, the
      association of EAT with RHT is reported.

PMID- 26317387
TI  - Analysis of SLITRK1 in Japanese patients with Tourette syndrome using a next
      generation sequencer.
AB  - The SLITRK1 (Slit and Trk-like 1) gene has been suggested to be a promising
      candidate for Tourette syndrome (TS) since the first report that identified its
      two rare variants adjacent to the chromosome inversion in a TS child with inv(13)
      (q31.1;q33.1). A series of replication studies have been carried out, whereas the
      role of the gene has not been elucidated. The present study aimed to determine
      whether the two or novel nonsynonymous variants were identified in Japanese TS
      patients and carry out an association analysis of the gene in a Japanese
      population. We did not observe the two or any novel nonsynonymous variants in the
      gene. In contrast, a significant difference was observed in the distributions of
      the haplotypes consisting of rs9546538, rs9531520, and rs9593835 between the
      patients and the controls. This result may partially support the implication of
      SLITRK1 in the pathogenesis of TS, warranting further studies of the gene. 

PMID- 26317388
TI  - Methodological guidance for systematic reviews of observational epidemiological
      studies reporting prevalence and cumulative incidence data.
AB  - AIM: There currently does not exist guidance for authors aiming to undertake
      systematic reviews of observational epidemiological studies, such as those
      reporting prevalence and incidence information. These reviews are particularly
      useful to measure global disease burden and changes in disease over time. The aim
      of this article is to provide guidance for conducting these types of reviews.
      METHODS: A methodological working group of the Joanna Briggs Institute, Adelaide,
      South Australia, Australia, was formed to create guidance for conducting
      systematic reviews of studies reporting prevalence and cumulative incidence
      information. All methodological output of the group was subject to peer review
      and feedback by members of the international evidence synthesis community.
      RESULTS: Systematic reviews of prevalence and incidence data should follow the
      same structured steps as systematic reviews of effectiveness. However, many of
      these steps need to be tailored for this type of evidence, particularly
      surrounding the stages of critical appraisal and synthesis. CONCLUSION:
      Prevalence and incidence systematic review and meta-analysis is an emerging
      methodology in the field of evidence synthesis. These reviews can provide useful
      information for healthcare professionals and policymakers on the burden of
      disease, show changes and trends over time in disease, and inform geographical
      distributions of disease and conditions.

PMID- 26317389
TI  - A Histological Snapshot of Hypothetical Multistep Progression From Nevus Sebaceus
      to Invasive Syringocystadenocarcinoma Papilliferum.
AB  - Syringocystadenocarcinoma papilliferum (SCACP) is an extremely rare adnexal
      neoplasm, believed to arise in a preexisting nevus sebaceus of Jadassohn (NSJ)
      through a multistep progression process. This hypothetical process involves an
      NSJ giving rise to syringocystadenoma papilliferum, which then presumably
      undergoes malignant transformation in rare circumstances to give rise to SCACP in
      situ, which finally progresses to an invasive SCACP. Of the 30 SCACP cases
      reported so far, none have documented the process from a birthmark to the final
      invasive lesion, with histological evidence of each step, in a single tumor.
      Here, the authors report just such a case. A 74-year-old man presented with a
      recently enlarging birthmark on the scalp. Excisional biopsy showed an invasive
      SCACP, in the background of SCACP in situ, syringocystadenoma papilliferum, and
      NSJ. Furthermore, this tumor showed a concurrent pigmented trichoblastoma and
      histological evidence of lymphovascular invasion, events that have not been
      documented with SCACP. Interestingly, all these component lesions were present on
      a single histological section of this solitary tumor. Regional lymph node
      metastasis, a rare occurrence in SCACP, was also present in this remarkable case.
      The authors discuss the implications of these findings in light of the review of
      relevant literature. 

PMID- 26317390
TI  - Neutrophilic Epitheliotropism is a Histopathological Clue to Neutrophilic
      Urticarial Dermatosis.
AB  - BACKGROUND: Neutrophilic urticarial dermatosis (NUD) comprises a particular
      autoinflammatory condition within the spectrum of aseptic neutrophilic dermatoses
      characterized by a distinct urticarial eruption clinically and a neutrophilic
      dermatosis histopathologically. OBJECTIVE: In this study, we reviewed skin
      biopsies of lesional skin of patients seen in our outpatient clinic for
      autoimmune dermatoses and in allergy department from 1982 to 2014 that fulfilled
      these criteria. METHODS: A total of 77 biopsies from 50 patients were analyzed
      histopathologically. Included were cases of Schnitzler syndrome, Still disease,
      systemic lupus erythematosus, Sjogren syndrome, cryopyrin-associated periodic
      syndrome, primary biliary cirrhosis, inflammatory bowel disease, and those that
      had signs of systemic inflammation not otherwise specified, that is, fever,
      arthritis, leukocytosis, and elevated erythrocyte sedimentation rate. A control
      cohort was defined as including a total of 70 biopsies from 50 patients
      comprising neutrophilic urticaria (pressure-induced and not pressure-induced),
      conventional urticaria, lupus erythematosus expressing neutrophils, and
      exanthematous drug reaction of macular type expressing neutrophils. RESULTS: Skin
      biopsies of NUD revealed a perivascular and interstitial neutrophilic infiltrate
      focally extending into the epithelia of epidermis, hair follicles, sebaceous and
      sweat glands, a feature which we termed neutrophilic epitheliotropism. This
      neutrophilic epitheliotropism proved to be of high sensitivity (83.1%) and lower
      specificity (74.3%). The histological findings could be substantiated by
      immunohistochemical markers for leukocytes (elastase and myeloperoxidase), in
      particular in cases where neutrophils showed uncharacteristic band-like nuclei.
      CONCLUSIONS: Neutrophilic epitheliotropism is a new sensitive and specific
      histopathological clue for NUD, a histopathological reaction pattern within the
      spectrum of neutrophilic dermatoses that needs to be differentiated from
      conventional urticaria.

PMID- 26317391
TI  - Probiotic Bacillus spp. in Soy-Curd: Nutritional, Rheological, Sensory, and
      Antioxidant Properties.
AB  - The focus of this study was to coculture probiotic Bacillus spp. with dairy
      starter cultures namely, Streptococcus thermophilus and Lactobacillus bulgaricus
      for enhanced nutritional properties of soy-curd. Subsequently, rheological,
      sensory, and antioxidant properties of soy-curd along with mineral as well as
      fatty acid composition were analyzed. Data revealed an increase in the cell
      viability of probiotic Bacillus spp. on coculturing rather than as mono-culture.
      Proximate analysis showed higher nutritional value along with increased trace
      elements. UFA/SFA ratio, rheology, and sensory properties of probiotic soy-curd
      were in the acceptable range. Probiotic soy-curd showed higher antioxidant
      activity as measured by the ability to scavenge free radicals. No significant
      difference in the overall quality within the probiotic products was observed.
      However, B. flexus MCC2427 cocultured product displayed slightly better
      attributes than other samples. In general, the results suggest that soy-curd can
      be a suitable carrier for probiotic Bacillus spp. and the enhanced nutritional
      and antioxidant properties could be of additional advantage to combat
      malnutrition problem. PRACTICAL APPLICATION: In order to supply consumers with
      intriguing probiotic products for improving health benefits, several criteria
      including technological and functional properties should be considered as a
      quality control measures. Further, a meaningful level of probiotics has to be
      viable to exhibit beneficial effect. Hence, present work has been carried out to
      improve the quality of soy-curd by supplementation of probiotic Bacillus spp.
      These Bacillus spp. are well characterized native probiotic cultures with
      potential functional attributes including antimicrobial, antioxidant,
      anticholesterol activity (Shobharani and Halami 2014). Hence, the application of
      these cultures will encourage for development of food product with wider health
      benefits.

PMID- 26317393
TI  - Comparison of Two Methods for Estimating Adjustable One-Point Cane Length in
      Community-Dwelling Older Adults.
AB  - BACKGROUND AND PURPOSE: Our aim is to estimate inter-observer reliability, test
      retest reliability, anthropometric and biomechanical adequacy and minimal
      detectable change when measuring the length of single-point adjustable canes in
      community-dwelling older adults. METHODS: There are 112 participants in the
      study. They are men and women, aged 60 years and over, who were attending an
      outpatient community health centre. An exploratory study design was used.
      Participants underwent two assessments within the same day by two independent
      observers and by the same observer at an interval of 15-45 days. Two measures
      were used to establish the length of a single-point adjustable cane: the distance
      from the distal wrist crease to the floor (WF) and the distance from the top of
      the greater trochanter of the femur to the floor (TF). Each individual was fitted
      according to these two measures, and elbow flexion angle was measured. RESULTS
      AND DISCUSSION: Inter-observer reliability and the test-retest reliability were
      high in both TF (ICC3.1  = 0.918 and ICC2.1  = 0.935) and WF measures (ICC3.1  =
      0.967 and ICC2.1  = 0.960). Only 1% of the individuals kept an elbow flexion
      angle within the standard recommendation of 30 degrees  +/- 10 degrees  when the
      cane length was determined by the TF measure, and 30% of the participants when
      the cane was determined by the WF measure. The minimal detectable cane length
      change was 2.2 cm. CONCLUSION: Our results suggest that, even though both
      measures are reliable, cane length determined by WF distance is more appropriate
      to keep the elbow flexion angle within the standard recommendation. The minimal
      detectable change corresponds to approximately a hole in the cane adjustment.
      Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 26317392
TI  - Identifying Driver Genomic Alterations in Cancers by Searching Minimum-Weight,
      Mutually Exclusive Sets.
AB  - An important goal of cancer genomic research is to identify the driving pathways
      underlying disease mechanisms and the heterogeneity of cancers. It is well known
      that somatic genome alterations (SGAs) affecting the genes that encode the
      proteins within a common signaling pathway exhibit mutual exclusivity, in which
      these SGAs usually do not co-occur in a tumor. With some success, this
      characteristic has been utilized as an objective function to guide the search for
      driver mutations within a pathway. However, mutual exclusivity alone is not
      sufficient to indicate that genes affected by such SGAs are in common pathways.
      Here, we propose a novel, signal-oriented framework for identifying driver SGAs.
      First, we identify the perturbed cellular signals by mining the gene expression
      data. Next, we search for a set of SGA events that carries strong information
      with respect to such perturbed signals while exhibiting mutual exclusivity.
      Finally, we design and implement an efficient exact algorithm to solve an NP-hard
      problem encountered in our approach. We apply this framework to the ovarian and
      glioblastoma tumor data available at the TCGA database, and perform systematic
      evaluations. Our results indicate that the signal-oriented approach enhances the
      ability to find informative sets of driver SGAs that likely constitute signaling
      pathways. 

PMID- 26317394
TI  - A Cyclodextrin-Based Photoresponsive Molecular Gate that Functions Independently
      of Either Solvent or Potentially Competitive Guests.
AB  - The photoinduced interconversion between cinnamido-substituted cyclodextrins
      constitutes a gating switch through which the substituent moves to open or block
      access to the cyclodextrin cavity. Most unusually for a cyclodextrin-based
      device, the operation of this gate is solvent-independent and unaffected by
      potentially competitive guests. It occurs in MeOH and DMSO, as well as in water.
      This contrasts with other cyclodextrin inclusion phenomena that are usually
      driven by hydrophobic effects and limited to aqueous media. 

PMID- 26317396
TI  - Ensemble summary statistics as a basis for rapid visual categorization.
AB  - Ensemble summary statistics represent multiple objects on the high level of
      abstraction-that is, without representing individual features and ignoring
      spatial organization. This makes them especially useful for the rapid visual
      categorization of multiple objects of different types that are intermixed in
      space. Rapid categorization implies our ability to judge at one brief glance
      whether all visible objects represent different types or just variants of one
      type. A framework presented here states that processes resembling statistical
      tests can underlie that categorization. At an early stage (primary
      categorization), when independent ensemble properties are distributed along a
      single sensory dimension, the shape of that distribution is tested in order to
      establish whether all features can be represented by a single or multiple peaks.
      When primary categories are separated, the visual system either reiterates the
      shape test to recognize subcategories (in-depth processing) or implements mean
      comparison tests to match several primary categories along a new dimension. Rapid
      categorization is not free from processing limitations; the role of selective
      attention in categorization is discussed in light of these limitations. 

PMID- 26317395
TI  - alpha/beta-Peptide Foldamers Targeting Intracellular Protein-Protein Interactions
      with Activity in Living Cells.
AB  - Peptides can be developed as effective antagonists of protein-protein
      interactions, but conventional peptides (i.e., oligomers of l-alpha-amino acids)
      suffer from significant limitations in vivo. Short half-lives due to rapid
      proteolytic degradation and an inability to cross cell membranes often preclude
      biological applications of peptides. Oligomers that contain both alpha- and beta
      amino acid residues ("alpha/beta-peptides") manifest decreased susceptibility to
      proteolytic degradation, and when properly designed these unnatural oligomers can
      mimic the protein-recognition properties of analogous "alpha-peptides". This
      report documents an extension of the alpha/beta-peptide approach to target
      intracellular protein-protein interactions. Specifically, we have generated
      alpha/beta-peptides based on a "stapled" Bim BH3 alpha-peptide, which contains a
      hydrocarbon cross-link to enhance alpha-helix stability. We show that a stapled
      alpha/beta-peptide can structurally and functionally mimic the parent stapled
      alpha-peptide in its ability to enter certain types of cells and block protein
      protein interactions associated with apoptotic signaling. However, the alpha/beta
      peptide is nearly 100-fold more resistant to proteolysis than is the parent
      stapled alpha-peptide. These results show that backbone modification, a strategy
      that has received relatively little attention in terms of peptide engineering for
      biomedical applications, can be combined with more commonly deployed peripheral
      modifications such as side chain cross-linking to produce synergistic benefits. 

PMID- 26317397
TI  - Use of random forest in FTIR analysis of LDL cholesterol and tri-glycerides for
      hyperlipidemia.
AB  - A quantitative determination method for the diagnosis of hyperlipidemia was
      developed using Fourier transform infrared (FTIR) spectroscopy. Random forest
      (RF) was demonstrated as a potential multivariate algorithm for the FTIR analysis
      of low-density lipoprotein cholesterol (LDL-C) and tri-glycerides (TG) in human
      serum samples. The informative wavebands for LDL-C and TG were selected based on
      the Gini importance. The selected wavebands were mainly within the fingerprint
      region. The RF modeling results were better than those derived using PLS in
      validation process, because the chance for over-fitting was possibly eliminated
      in RF algorithm. ARF also demonstrated favorable results in the test process. The
      prospective model exhibited a higher than 90% true prediction in
      negative/positive properties for male and female samples. These clinical
      statistical results indicated the optimization of RF algorithm performed
      accurately in the FTIR determination of LDL-C and TG. RF is evaluated as a
      promising tool for diagnosing and controlling hyperlipidemia in populations. The
      parameter optimization methodology is useful in the improving model accuracy
      using FTIR spectroscopic technology.

PMID- 26317398
TI  - Immunological markers for prognostication in cytogenetically normal acute myeloid
      leukemia.

PMID- 26317400
TI  - Photocatalytic One-Pot Synthesis of Homoallyl Ketones via a Norrish Type I
      Reaction of Cyclopentanones.
AB  - A photocatalytic synthesis of homoallyl ketones was achieved via a one-pot
      procedure starting from a Norrish Type I reaction of cyclopentanones, followed by
      a decatungstate-catalyzed hydroacylation of electron-deficient olefins by the
      resulting 4-pentenals. The site-selective formyl H-abstraction in the second step
      can be explained by radical polar effects in the transition state. 

PMID- 26317399
TI  - Encapsulated Brucella ovis Lacking a Putative ATP-Binding Cassette Transporter
      (DeltaabcBA) Protects against Wild Type Brucella ovis in Rams.
AB  - This study aimed to evaluate protection induced by the vaccine candidate B. ovis
      DeltaabcBA against experimental challenge with wild type B. ovis in rams. Rams
      were subcutaneously immunized with B. ovis DeltaabcBA encapsulated with sterile
      alginate or with the non encapsulated vaccine strain. Serum, urine, and semen
      samples were collected during two months after immunization. The rams were then
      challenged with wild type B. ovis (ATCC25840), and the results were compared to
      non immunized and experimentally challenged rams. Immunization, particularly with
      encapsulated B. ovis DeltaabcBA, prevented infection, secretion of wild type B.
      ovis in the semen and urine, shedding of neutrophils in the semen, and the
      development of clinical changes, gross and microscopic lesions induced by the
      wild type B. ovis reference strain. Collectively, our data indicates that the B.
      ovis DeltaabcBA strain is an exceptionally good vaccine strain for preventing
      brucellosis caused by B. ovis infection in rams. 

PMID- 26317401
TI  - Has Wild Poliovirus Been Eliminated from Nigeria?
AB  - Wild poliovirus type 3 (WPV3) has not been seen anywhere since the last case of
      WPV3-associated paralysis in Nigeria in November 2012. At the time of writing,
      the most recent case of wild poliovirus type 1 (WPV1) in Nigeria occurred in July
      2014, and WPV1 has not been seen in Africa since a case in Somalia in August
      2014. No cases associated with circulating vaccine-derived type 2 poliovirus
      (cVDPV2) have been detected in Nigeria since November 2014. Has WPV1 been
      eliminated from Africa? Has WPV3 been eradicated globally? Has Nigeria
      interrupted cVDPV2 transmission? These questions are difficult because polio
      surveillance is based on paralysis and paralysis only occurs in a small fraction
      of infections. This report provides estimates for the probabilities of poliovirus
      elimination in Nigeria given available data as of March 31, 2015. It is based on
      a model of disease transmission that is built from historical polio incidence
      rates and is designed to represent the uncertainties in transmission dynamics and
      poliovirus detection that are fundamental to interpreting long time periods
      without cases. The model estimates that, as of March 31, 2015, the probability of
      WPV1 elimination in Nigeria is 84%, and that if WPV1 has not been eliminated, a
      new case will be detected with 99% probability by the end of 2015. The
      probability of WPV3 elimination (and thus global eradication) is > 99%. However,
      it is unlikely that the ongoing transmission of cVDPV2 has been interrupted; the
      probability of cVDPV2 elimination rises to 83% if no new cases are detected by
      April 2016. 

PMID- 26317402
TI  - A Novel Poly(ionic liquid) Interface-Free Two-Dimensional Monolithic Material for
      the Separation of Multiple Types of Glycoproteins.
AB  - Currently, many types of affinity materials have been developed for the
      enrichment of glycoproteins potentially considered to be clinical biomarkers;
      however, they can not effectively distinguish between different glycoproteins and
      thus lack the functionality that may be the key to the diagnosis of specific
      diseases. In the present work, a novel interface-free 2D monolithic material has
      been developed for the separation of multiple types of glycoproteins, in which
      boronate-functionalized graphene acts as preconcentration segment and
      poly(guanidinium ionic liquid) acts as separation segment. The resultant 2D
      material was characterized by X-ray photoelectron spectroscopy, elemental
      analysis, and electroosmotic flow analysis to demonstrate successful modification
      at each step. The performance of this 2D material was evaluated by capillary
      electrochromatography and allowed the successful online concentration and
      separation of five standard glycoproteins. The high separation efficiency can be
      largely attributed to the good orthogonality of boronate-functionalized graphene
      monolith and poly(guanidinium ionic liquid) monolith. 

PMID- 26317403
TI  - The Hos2 Histone Deacetylase Controls Ustilago maydis Virulence through Direct
      Regulation of Mating-Type Genes.
AB  - Morphological changes are critical for host colonisation in plant pathogenic
      fungi. These changes occur at specific stages of their pathogenic cycle in
      response to environmental signals and are mediated by transcription factors,
      which act as master regulators. Histone deacetylases (HDACs) play crucial roles
      in regulating gene expression, for example by locally modulating the
      accessibility of chromatin to transcriptional regulators. It has been reported
      that HDACs play important roles in the virulence of plant fungi. However, the
      specific environment-sensing pathways that control fungal virulence via HDACs
      remain poorly characterised. Here we address this question using the maize
      pathogen Ustilago maydis. We find that the HDAC Hos2 is required for the
      dimorphic switch and pathogenic development in U. maydis. The deletion of hos2
      abolishes the cAMP-dependent expression of mating type genes. Moreover, ChIP
      experiments detect Hos2 binding to the gene bodies of mating-type genes, which
      increases in proportion to their expression level following cAMP addition. These
      observations suggest that Hos2 acts as a downstream component of the cAMP-PKA
      pathway to control the expression of mating-type genes. Interestingly, we found
      that Clr3, another HDAC present in U. maydis, also contributes to the cAMP
      dependent regulation of mating-type gene expression, demonstrating that Hos2 is
      not the only HDAC involved in this control system. Overall, our results provide
      new insights into the role of HDACs in fungal phytopathogenesis. 

PMID- 26317404
TI  - Psychometric Properties of the Obsessive-Compulsive Inventory-Child Version (OCI
      CV) in Chilean Children and Adolescents.
AB  - In recent years, there has been a considerable increase in the development of
      assessment tools for obsessive-compulsive symptomatology in children and
      adolescents. The Obsessive Compulsive Inventory-Child Version (OCI-CV) is a well
      established assessment self-report, with special interest for the assessment of
      dimensions of Obsessive Compulsive Disorder (OCD). This instrument has shown to
      be useful for clinical and non-clinical populations in two languages (English and
      European Spanish). Thus, the aim of this study was to analyze the psychometric
      properties of the OCI-CV in a Chilean community sample. The sample consisted of
      816 children and adolescents with a mean age of 14.54 years (SD = 2.21; range =
      10-18 years). Factor structure, internal consistency, test-retest reliability,
      convergent/divergent validity, and gender/age differences were examined.
      Confirmatory factor analysis showed a 6-factor structure (Doubting/Checking,
      Obsessing, Hoarding, Washing, Ordering, and Neutralizing) with one second-order
      factor. Good estimates of reliability (including internal consistency and test
      retest), evidence supporting the validity, and small age and gender differences
      (higher levels of OCD symptomatology among older participants and women,
      respectively) are found. The OCI-CV is also an adequate scale for the assessment
      of obsessions and compulsions in a general population of Chilean children and
      adolescents. 

PMID- 26317405
TI  - Degradable Polycaprolactone and Polylactide Homopolymer and Block Copolymer
      Brushes Prepared by Surface-Initiated Polymerization with Triazabicyclodecene and
      Zirconium Catalysts.
AB  - Surface-initiated ring-opening polymerization (SI-ROP) of polycaprolactone (PCL)
      and polylactide (PLA) polymer brushes with controlled degradation rates were
      prepared on oxide substrates. PCL brushes were polymerized from hydroxyl
      terminated monolayers utilizing triazabicyclodecene (TBD) as the polymerization
      catalyst. A consistent brush thickness of 40 nm could be achieved with a
      reproducible unique crystalline morphology. The organocatalyzed PCL brushes were
      chain extended using lactide in the presence of zirconium n-butoxide to
      successfully grow PCL/PLA block copolymer (PCL-b-PLA) brushes with a final
      thickness of 55 nm. The degradation properties of "grafted from" PCL brush and
      the PCL-b-PLA brush were compared to "grafted to" PCL brushes, and we observed
      that the brush density plays a major role in degradation kinetics. Solutions of
      methanol/water at pH 14 were used to better solvate the brushes and increase the
      kinetics of degradation. This framework enables a control of degradation that
      allows for the precise removal of these coatings. 

PMID- 26317406
TI  - Reporting Quality of Systematic Reviews and Meta-Analyses of Otorhinolaryngologic
      Articles Based on the PRISMA Statement.
AB  - BACKGROUND: Systematic reviews (SRs) and meta-analyses (MAs) provide the highest
      possible level of evidence. However, poor conduct or reporting of SRs and MAs may
      reduce their utility. The PRISMA Statement (Preferred Reporting Items for
      Systematic reviews and Meta-Analyses) was developed to help authors report their
      SRs and MAs adequately. OBJECTIVES: Our objectives were to (1) evaluate the
      quality of reporting of SRs and MAs and their abstracts in otorhinolaryngologic
      literature using the PRISMA and PRISMA for Abstracts checklists, respectively,
      (2) compare the quality of reporting of SRs and MAs published in Ear Nose Throat
      (ENT) journals to the quality of SRs and MAs published in the 'gold standard'
      Cochrane Database of Systematic Reviews (CDSR), and (3) formulate recommendations
      to improve reporting of SRs and MAs in ENT journals. METHODS: On September 3,
      2014, we searched the Pubmed database using a combination of filters to retrieve
      SRs and MAs on otorhinolaryngologic topics published in 2012 and 2013 in the top
      5 ENT journals (ISI Web of Knowledge 2013) or CDSR and relevant articles were
      selected. We assessed how many, and which, PRISMA (for Abstracts) items were
      reported adequately per journal type. RESULTS: We identified large differences in
      the reporting of individual items between the two journal types with room for
      improvement. In general, SRs and MAs published in ENT journals (n = 31) reported
      a median of 54.4% of the PRISMA items adequately, whereas the 49 articles
      published in the CDSR reported a median of 100.0 adequately (difference
      statistically significant, p < 0.001). For abstracts, medians of 41.7% for ENT
      journals and 75.0% for the CDSR were found (p < 0.001). CONCLUSION: The reporting
      of SRs and MAs in ENT journals leaves room for improvement and would benefit if
      the PRISMA Statement were endorsed by these journals.

PMID- 26317407
TI  - Quantitative analysis of histone H3 and H4 post-translational modifications in
      doxorubicin-resistant leukemia cells.
AB  - The epigenetic remodeling of chromatin through histone modifications has been
      widely implicated in drug resistance of cancer cells. However, whether epigenetic
      mechanisms contribute specifically to doxorubicin resistance in leukemia has not
      been carefully examined. Using a stable and sensitive workflow based on LC-MS, we
      quantitatively compared the extents of methylation and acetylation of histone H3
      and H4 in acute leukemia cell line HL60 and its doxorubicin-resistant derivative,
      HL60/ADR, as well as the chronic leukemia cell line K562 and its doxorubicin
      resistant derivative, K562/ADR. We found that increased levels of H3K9
      methylation, H3K14, H3K18 and H3K23 acetylation, and potentially H4K20
      methylation, are associated with drug resistance in both cells. Our results
      demonstrated that the doxorubicin-resistant acute and chronic leukemia cell lines
      may share a common epigenetic mechanism that involves a combination of
      transcriptional activation and silencing.

PMID- 26317408
TI  - 180 degrees  Ferroelectric Stripe Nanodomains in BiFeO3 Thin Films.
AB  - There is growing evidence that domain walls in ferroics can possess emergent
      properties that are absent in the bulk. For example, 180 degrees  ferroelectric
      domain walls in the ferroelectric-antiferromagnetic BiFeO3 are particularly
      interesting because they have been predicted to possess a range of intriguing
      behaviors, including electronic conduction and enhanced magnetization. To date,
      however, ordered arrays of such domain structures have not been reported. Here,
      we report the observation of 180 degrees  stripe nanodomains in (110)-oriented
      BiFeO3 thin films grown on orthorhombic GdScO3 (010)O substrates and their impact
      on exchange coupling to metallic ferromagnets. Nanoscale ferroelectric 180
      degrees  stripe domains with {112} domain walls were observed in films <32 nm
      thick. With increasing film thickness, we observed a domain structure crossover
      from the depolarization field-driven 180 degrees  stripe nanodomains to 71
      degrees  ferroelastic domains determined by the elastic energy. These 180 degrees
      domain walls (which are typically cylindrical or meandering in nature due to a
      lack of strong anisotropy associated with the energy of such walls) are found to
      be highly ordered. Additional studies of Co0.9Fe0.1/BiFeO3 heterostructures
      reveal exchange bias and exchange enhancement in heterostructures based on BiFeO3
      with 180 degrees  domain walls and an absence of exchange bias in
      heterostructures based on BiFeO3 with 71 degrees  domain walls; suggesting that
      the 180 degrees  domain walls could be the possible source for pinned
      uncompensated spins that give rise to exchange bias. This is further confirmed by
      X-ray circular magnetic dichroism studies, which demonstrate that films with
      predominantly 180 degrees  domain walls have larger magnetization than those with
      primarily 71 degrees  domain walls. Our results could be useful to extract the
      structure of domain walls and to explore domain wall functionalities in BiFeO3. 

PMID- 26317409
TI  - Citing a Data Repository: A Case Study of the Protein Data Bank.
AB  - The Protein Data Bank (PDB) is the worldwide repository of 3D structures of
      proteins, nucleic acids and complex assemblies. The PDB's large corpus of data (>
      100,000 structures) and related citations provide a well-organized and extensive
      test set for developing and understanding data citation and access metrics. In
      this paper, we present a systematic investigation of how authors cite PDB as a
      data repository. We describe a novel metric based on information cascade
      constructed by exploring the citation network to measure influence between
      competing works and apply that to analyze different data citation practices to
      PDB. Based on this new metric, we found that the original publication of RCSB PDB
      in the year 2000 continues to attract most citations though many follow-up
      updates were published. None of these follow-up publications by members of the
      wwPDB organization can compete with the original publication in terms of
      citations and influence. Meanwhile, authors increasingly choose to use URLs of
      PDB in the text instead of citing PDB papers, leading to disruption of the growth
      of the literature citations. A comparison of data usage statistics and paper
      citations shows that PDB Web access is highly correlated with URL mentions in the
      text. The results reveal the trend of how authors cite a biomedical data
      repository and may provide useful insight of how to measure the impact of a data
      repository. 

PMID- 26317410
TI  - Structural Characterization and Immunostimulatory Activity of a Homogeneous
      Polysaccharide from Sinonovacula constricta.
AB  - Sinonovacula constricta has been widely used as a health food and medicine in
      China, Japan, and Korea. In the present study, a water-soluble polysaccharide
      fraction (SCP-1) was prepared from S. constricta by enzyme-assisted extraction
      and purification of chromatography with DEAE-52 cellulose anion-exchange column
      and Sephadex G-100 size exclusion column. On the basis of the analytical results
      of high-performance liquid chromatography, Fourier transform-infrared
      spectroscopy, methylation analysis, and NMR spectroscopy, SCP-1 was found to have
      an average molecular weight of 15.63 kDa and a linear backbone of (1->4)-linked
      alpha-D-Glcp residue with one branch, alpha-D-Glcp, attached to the main chain by
      a (1->6) glycosidic bond at every five alpha-D-Glcp units. Furthermore, it was
      found that SCP-1 could significantly increase the viability of macrophages,
      enhance the capability of macrophage phagocytosis, increase the activity of acid
      phosphatase, and promote the production of nitric oxide, mouse tumor necrosis
      factor (TNF)-alpha, mouse interferon (IFN)-gamma, and mouse interleukin (IL)
      1beta. The results suggest that SCP-1 possesses potent immunomodulating effect
      and may be explored as a potential biological response modifier.

PMID- 26317412
TI  - Functional Characterization of Phalaenopsis aphrodite Flowering Genes PaFT1 and
      PaFD.
AB  - We show that the key flowering regulators encoded by Phalaenopsis aphrodite
      FLOWERING LOCUS T1 (PaFT1) and PaFD share high sequence homologies to these from
      long-day flowering Arabidopsis and short-day flowering rice. Interestingly, PaFT1
      is specifically up-regulated during flowering inductive cooling treatment but is
      not subjected to control by photoperiod in P. aphrodite. Phloem or shoot apex
      specific expression of PaFT1 restores the late flowering of Arabidopsis ft
      mutants. Moreover, PaFT1 can suppress the delayed flowering caused by SHORT
      VEGATATIVE PHASE (SVP) overexpression as well as an active FRIGIDA (FRI) allele,
      indicating the functional conservation of flowering regulatory circuit in
      different plant species. PaFT1 promoter:GUS in Arabidopsis showed similar
      staining pattern to that of Arabidopsis FT in the leaves and guard cells but
      different in the shoot apex. A genomic clone or heat shock-inducible expression
      of PaFT1 is sufficient to the partial complementation of the ft mutants.
      Remarkably, ectopic PaFT1 expression also triggers precocious heading in rice. To
      further demonstrate the functional conservation of the flowering regulators, we
      show that PaFD, a bZIP transcription factor involved in flowering promotion,
      interacts with PaFT1, and PaFD partially complemented Arabidopsis fd mutants.
      Transgenic rice expressing PaFD also flowered early with increased expression of
      rice homologues of APETALA1 (AP1). Consistently, PaFT1 knock-down Phalaenopsis
      plants generated by virus-induced gene silencing exhibit delayed spiking. These
      studies suggest functional conservation of FT and FD genes, which may have
      evolved and integrated into distinct regulatory circuits in monopodial orchids,
      Arabidopsis and rice that promote flowering under their own inductive conditions.

PMID- 26317413
TI  - Prevalence of Congenital Heart Disease in Xinjiang Multi-Ethnic Region of China.
AB  - BACKGROUND: The prevalence and risk factors of congenital heart disease among
      Xinjiang, northwestern part of China is currently unknown. METHODS: This multiple
      ethnic, community-based, cross-sectional study was conducted to estimate the
      prevalence and distribution of congenital heart disease (CHD) in Xinjiang,
      northwestern part of China. Four major ethnics, Uygur, Han, Kazak, and Hui
      children in this region were investigated during February 2010 and May 2012.
      RESULTS: A total of 14,530 children (0-18 yr) were examined. Of these children,
      240 (boys, 43.8%, and girls, 56.3%) were identified with CHD, giving an overall
      prevalence of 16.50/00 (17.70/00 in Uygur, 6.90/00 in Han, 11.40/00 in Kazak, and
      38.10/00 in Hui Chinese, respectively). Ventricular septal defect (VSD, 29.2%),
      atrial septal defect (ASD, 20.8%), patent ductus arteriosus (PDA, 13.7%),
      acleistocardia (13.7%), Bicuspid aortic valve (7.9%), pulmonary valve stenosis
      (5.4%), and tetralogy of fallot (TOF, 4.2%) were common cyanotic and cyanotic
      defects observed. Compared to non-CHD children, children with CHD had a higher
      percentage of history of abortion, CHD history of family, consanguinity and
      premature birth (all P<0.05). In CHD children, 24% of mothers caught a cold, 10%
      had a febrile illness and 6.7% received antibiotic treatment during the first
      trimester of pregnancy, that were higher than non-CHD group (all P<0.05).
      CONCLUSION: The overall prevalence of CHD in four ethnic children at ages 0-18 yr
      in Xinjiang was 16.50/00. VSD, ASD and TOF were the most common acyanotic and
      cyanotic congenital heart defects, respectively. This study also identified some
      modifiable risk factors that may contribute to the incidence of CHD among the 4
      ethnic groups.

PMID- 26317411
TI  - SNP-SNP interaction analysis of NF-kappaB signaling pathway on breast cancer
      survival.
AB  - In breast cancer, constitutive activation of NF-kappaB has been reported,
      however, the impact of genetic variation of the pathway on patient prognosis has
      been little studied. Furthermore, a combination of genetic variants, rather than
      single polymorphisms, may affect disease prognosis. Here, in an extensive dataset
      (n = 30,431) from the Breast Cancer Association Consortium, we investigated the
      association of 917 SNPs in 75 genes in the NF-kappaB pathway with breast cancer
      prognosis. We explored SNP-SNP interactions on survival using the likelihood
      ratio test comparing multivariate Cox' regression models of SNP pairs without and
      with an interaction term. We found two interacting pairs associating with
      prognosis: patients simultaneously homozygous for the rare alleles of rs5996080
      and rs7973914 had worse survival (HRinteraction 6.98, 95% CI=3.3-14.4, P=1.42E
      07), and patients carrying at least one rare allele for rs17243893 and rs57890595
      had better survival (HRinteraction 0.51, 95% CI=0.3-0.6, P = 2.19E-05). Based on
      in silico functional analyses and literature, we speculate that the rs5996080 and
      rs7973914 loci may affect the BAFFR and TNFR1/TNFR3 receptors and breast cancer
      survival, possibly by disturbing both the canonical and non-canonical NF-kappaB
      pathways or their dynamics, whereas, rs17243893-rs57890595 interaction on
      survival may be mediated through TRAF2-TRAIL-R4 interplay. These results warrant
      further validation and functional analyses. 

PMID- 26317414
TI  - Investigation and Analysis of Genetic Diversity of Diospyros Germplasms Using
      SCoT Molecular Markers in Guangxi.
AB  - BACKGROUND: Knowledge about genetic diversity and relationships among germplasms
      could be an invaluable aid in diospyros improvement strategies. METHODS: This
      study was designed to analyze the genetic diversity and relationship of local and
      natural varieties in Guangxi Zhuang Autonomous Region of China using start codon
      targeted polymorphism (SCoT) markers. The accessions of 95 diospyros germplasms
      belonging to four species Diospyros kaki Thunb, D. oleifera Cheng, D. kaki var.
      silverstris Mak, and D. lotus Linn were collected from different eco-climatic
      zones in Guangxi and were analyzed using SCoT markers. RESULTS: Results indicated
      that the accessions of 95 diospyros germplasms could be distinguished using SCoT
      markers, and were divided into three groups at similarity coefficient of 0.608;
      these germplasms that belong to the same species were clustered together; of
      these, the degree of genetic diversity of the natural D. kaki var. silverstris
      Mak population was richest among the four species; the geographical distance
      showed that the 12 natural populations of D. kaki var. silverstris Mak were
      divided into two groups at similarity coefficient of 0.19. Meanwhile, in order to
      further verify the stable and useful of SCoT markers in diospyros germplasms, SSR
      markers were also used in current research to analyze the genetic diversity and
      relationship in the same diospyros germplasms. Once again, majority of germplasms
      that belong to the same species were clustered together. Thus SCoT markers were
      stable and especially useful for analysis of the genetic diversity and
      relationship in diospyros germplasms. DISCUSSION: The molecular characterization
      and diversity assessment of diospyros were very important for conservation of
      diospyros germplasm resources, meanwhile for diospyros improvement.

PMID- 26317415
TI  - A Subregion of Reelin Suppresses Lipoprotein-Induced Cholesterol Accumulation in
      Macrophages.
AB  - Activation of apolipoprotein E receptor-2 (apoER2) and very low density
      lipoprotein receptor (VLDLR) inhibits foam cell formation. Reelin is a ligand of
      these receptors. Here we generated two reelin subregions containing the receptor
      binding domain with or without its C-terminal region (R5-6C and R5-6,
      respectively) and studied the impact of these peptides on macrophage cholesterol
      metabolism. We found that both R5-6C and R5-6 can be secreted by cells. Purified
      R5-6 protein can bind apoER2 and VLDLR. Overexpression of apoER2 in macrophages
      increased the amount of R5-6 bound to the cell surface. Treatment of macrophages
      with 0.2 MUg/ml R5-6 elevated ATP binding cassette A1 (ABCA1) protein level by
      ~72% and apoAI-mediated cholesterol efflux by ~39%. In addition, the medium
      harvested from cells overexpressing R5-6 or R5-6C (R5-6- and R5-6C-conditioned
      media, respectively) also up-regulated ABCA1 protein expression, which was
      associated with accelerated cholesterol efflux and enhanced phosphorylation of
      phosphatidylinositol 3 kinase (PI3K) and specificity protein-1 (Sp1) in
      macrophages. The increased ABCA1 expression and cholesterol efflux by R5-6- and
      R5-6C-conditioned media were diminished by Sp1 or PI3K inhibitors mithramycin A
      and LY294002. Further, the cholesterol accumulation induced by apoB-containing,
      apoE-free lipoproteins was significantly less in macrophages incubated with R5-6-
      or R5-6C-conditioned medium than in those incubated with control conditioned
      medium. Knockdown of apoER2 or VLDLR attenuated the inhibitory role of R5-6
      conditioned medium against lipoprotein-induced cholesterol accumulation. These
      results suggest that the reelin subregion R5-6 can serve as a tool for studying
      the role of apoER2 and VLDLR in atherogenesis. 

PMID- 26317416
TI  - 14-3-3 Proteins Buffer Intracellular Calcium Sensing Receptors to Constrain
      Signaling.
AB  - Calcium sensing receptors (CaSR) interact with 14-3-3 binding proteins at a
      carboxyl terminal arginine-rich motif. Mutations identified in patients with
      familial hypocalciuric hypercalcemia, autosomal dominant hypocalcemia,
      pancreatitis or idiopathic epilepsy support the functional importance of this
      motif. We combined total internal reflection fluorescence microscopy and
      biochemical approaches to determine the mechanism of 14-3-3 protein regulation of
      CaSR signaling. Loss of 14-3-3 binding caused increased basal CaSR signaling and
      plasma membrane levels, and a significantly larger signaling-evoked increase in
      plasma membrane receptors. Block of core glycosylation with tunicamycin
      demonstrated that changes in plasma membrane CaSR levels were due to differences
      in exocytic rate. Western blotting to quantify time-dependent changes in
      maturation of expressed wt CaSR and a 14-3-3 protein binding-defective mutant
      demonstrated that signaling increases synthesis to maintain constant levels of
      the immaturely and maturely glycosylated forms. CaSR thus operates by a feed
      forward mechanism, whereby signaling not only induces anterograde trafficking of
      nascent receptors but also increases biosynthesis to maintain steady state levels
      of net cellular CaSR. Overall, these studies suggest that 14-3-3 binding at the
      carboxyl terminus provides an important buffering mechanism to increase the
      intracellular pool of CaSR available for signaling-evoked trafficking, but
      attenuates trafficking to control the dynamic range of responses to extracellular
      calcium. 

PMID- 26317417
TI  - The Uptake of Screening for Type 2 Diabetes and Prediabetes by Means of Glycated
      Hemoglobin versus the Oral Glucose Tolerance Test among 18 to 60-Year-Old People
      of South Asian Origin: A Comparative Study.
AB  - BACKGROUND: Direct comparisons of the effect of a glycated haemoglobin
      measurement or an oral glucose tolerance test on the uptake and yield of
      screening in people of South Asian origin have not been made. We evaluated this
      in 18 to 60-year-old South Asian Surinamese. MATERIALS AND METHODS: We invited
      3173 South Asian Surinamese for an oral glucose tolerance test between June 18th
      2009- December 31st 2009 and 2012 for a glycated hemoglobin measurement between
      April 19th 2010-November 11th, 2010. Participants were selected from 48 general
      practices in The Hague, The Netherlands. We used mixed models regression to
      analyse differences in response and participation between the groups. We
      described differences in characteristics of participants and calculated the yield
      as the percentage of all cases identified, if all invitees had been offered
      screening with the specified method. RESULTS: The response and participation in
      the glycated hemoglobin group was higher than in the group offered an oral
      glucose tolerance test (participation 23.9 vs. 19.3; OR: 1.30, 95%-confidence
      interval1.01-1.69). After adjustment for age and sex, characteristics of
      participants were similar for both groups. Overall, glycated hemoglobin
      identified a similar percentage of type 2 diabetes cases but a higher percentage
      of prediabetes cases, in the population than the oral glucose tolerance test.
      CONCLUSION: We found that glycated hemoglobin and the oral glucose tolerance test
      may be equally efficient for identification of type 2 diabetes in populations of
      South Asian origin. However, for programs aimed at identifying people at high
      risk of type 2 diabetes (i.e. with prediabetes), the oral glucose tolerance test
      may be a less efficient choice than glycated hemoglobin.

PMID- 26317418
TI  - Low miR-143/miR-145 Cluster Levels Induce Activin A Overexpression in Oral
      Squamous Cell Carcinomas, Which Contributes to Poor Prognosis.
AB  - Deregulated expression of activin A is reported in several tumors, but its
      biological functions in oral squamous cell carcinoma (OSCC) are unknown. Here, we
      investigate whether activin A can play a causal role in OSCCs. Activin A
      expression was assessed by qPCR and immunohistochemistry in OSCC tissues. Low
      activin A-expressing cells were treated with recombinant activin A and assessed
      for apoptosis, proliferation, adhesion, migration, invasion and epithelial
      mesenchymal transition (EMT). Those phenotypes were also evaluated in high
      activin A-expressing cells treated with follistatin (an activin A antagonist) or
      stably expressing shRNA targeting activin A. Transfections of microRNA mimics
      were performed to determine whether the overexpression of activin A is regulated
      by miR-143/miR-145 cluster. Activin A was overexpressed in OSCCs in comparison
      with normal oral mucosa, and high activin A levels were significantly associated
      with lymph node metastasis, tumor differentiation and poor survival. High activin
      A levels promoted multiple properties associated with malignant transformation,
      including decreased apoptosis and increased proliferation, migration, invasion
      and EMT. Both miR-143 and miR-145 were markedly downregulated in OSCC cell lines
      and in clinical specimens, and inversely correlated to activin A levels. Forced
      expression of miR-143 and miR-145 in OSCC cells significantly decreased the
      expression of activin A. Overexpression of activin A in OSCCs, which is
      controlled by downregulation of miR-143/miR-145 cluster, regulates apoptosis,
      proliferation and invasiveness, and it is clinically correlated with lymph node
      metastasis and poor survival. 

PMID- 26317419
TI  - Increased Nucleosomes and Neutrophil Activation Link to Disease Progression in
      Patients with Scrub Typhus but Not Murine Typhus in Laos.
AB  - Cell-mediated immunity is essential in protection against rickettsial illnesses,
      but the role of neutrophils in these intracellular vasculotropic infections
      remains unclear. This study analyzed the plasma levels of nucleosomes, FSAP
      activation (nucleosome-releasing factor), and neutrophil activation, as evidenced
      by neutrophil-elastase (ELA) complexes, in sympatric Lao patients with scrub
      typhus and murine typhus. In acute scrub typhus elevated nucleosome levels
      correlated with lower GCS scores, raised respiratory rate, jaundice and impaired
      liver function, whereas neutrophil activation correlated with fibrinolysis and
      high IL-8 plasma levels, a recently identified predictor of severe disease and
      mortality. Nucleosome and ELA complex levels were associated with a 4.8-fold and
      4-fold increased risk of developing severe scrub typhus, beyond cut off values of
      1,040 U/ml for nucleosomes and 275 U/ml for ELA complexes respectively. In murine
      typhus, nucleosome levels associated with pro-inflammatory cytokines and the
      duration of illness, while ELA complexes correlated strongly with inflammation
      markers, jaundice and increased respiratory rates. This study found strong
      correlations between circulating nucleosomes and neutrophil activation in
      patients with scrub typhus, but not murine typhus, providing indirect evidence
      that nucleosomes could originate from neutrophil extracellular trap (NET)
      degradation. High circulating plasma nucleosomes and ELA complexes represent
      independent risk factors for developing severe complications in scrub typhus. As
      nucleosomes and histones exposed on NETs are highly cytotoxic to endothelial
      cells and are strongly pro-coagulant, neutrophil-derived nucleosomes could
      contribute to vascular damage, the pro-coagulant state and exacerbation of
      disease in scrub typhus, thus indicating a detrimental role of neutrophil
      activation. The data suggest that increased neutrophil activation relates to
      disease progression and severe complications, and increased plasma levels of
      nucleosomes and ELA complexes represent independent risk factors for developing
      severe scrub typhus. 

PMID- 26317420
TI  - The Influence of Drivers and Barriers on Urban Adaptation and Mitigation Plans-An
      Empirical Analysis of European Cities.
AB  - Cities are recognised as key players in global adaptation and mitigation efforts
      because the majority of people live in cities. However, in Europe, which is
      highly urbanized and one of the most advanced regions in terms of environmental
      policies, there is considerable diversity in the regional distribution, ambition
      and scope of climate change responses. This paper explores potential factors
      contributing to such diversity in 200 large and medium-sized cities across 11
      European countries. We statistically investigate institutional, socio-economic,
      environmental and vulnerability characteristics of cities as potential drivers of
      or barriers to the development of urban climate change plans. Our results show
      that factors such as membership of climate networks, population size, GDP per
      capita and adaptive capacity act as drivers of mitigation and adaptation plans.
      By contrast, factors such as the unemployment rate, warmer summers, proximity to
      the coast and projected exposure to future climate impacts act as barriers. We
      see that, overall, it is predominantly large and prosperous cities that engage in
      climate planning, while vulnerable cities and those at risk of severe climate
      impacts in the future are less active. Our analysis suggests that climate change
      planning in European cities is not proactive, i.e. not significantly influenced
      by anticipated future impacts. Instead, we found that the current adaptive
      capacity of a city significantly relates to climate planning. Along with the need
      to further explore these relations, we see a need for more economic and
      institutional support for smaller and less resourceful cities and those at high
      risk from climate change impacts in the future. 

PMID- 26317421
TI  - Carbon/Nitrogen Imbalance Associated with Drought-Induced Leaf Senescence in
      Sorghum bicolor.
AB  - Drought stress triggers mature leaf senescence, which supports plant survival and
      remobilization of nutrients; yet leaf senescence also critically decreases post
      drought crop yield. Drought generally results in carbon/nitrogen imbalance, which
      is reflected in the increased carbon:nitrogen (C:N) ratio in mature leaves, and
      which has been shown to be involved in inducing leaf senescence under normal
      growth conditions. Yet the involvement of the carbon/nitrogen balance in
      regulation of drought-induced leaf senescence is unclear. To investigate the role
      of carbon/nitrogen balance in drought-induced senescence, sorghum seedlings were
      subjected to a gradual soil drought treatment. Leaf senescence symptoms and the
      C:N ratio, which was indicated by the ratio of non-structural carbohydrate to
      total N content, were monitored during drought progression. In this study, leaf
      senescence developed about 12 days after the start of drought treatment, as
      indicated by various senescence symptoms including decreasing photosynthesis,
      photosystem II photochemistry efficiency (Fv/Fm) and chlorophyll content, and by
      the differential expression of senescence marker genes. The C:N ratio was
      significantly enhanced 10 to 12 days into drought treatment. Leaf senescence
      occurred in the older (lower) leaves, which had higher C:N ratios, but not in the
      younger (upper) leaves, which had lower C:N ratios. In addition, a detached leaf
      assay was conducted to investigate the effect of carbon/nitrogen availability on
      drought-induced senescence. Exogenous application of excess sugar combined with
      limited nitrogen promoted drought-induced leaf senescence. Thus our results
      suggest that the carbon/nitrogen balance may be involved in the regulation of
      drought-induced leaf senescence. 

PMID- 26317422
TI  - Protracted Administration of L-Asparaginase in Maintenance Phase Is the Risk
      Factor for Hyperglycemia in Older Patients with Pediatric Acute Lymphoblastic
      Leukemia.
AB  - Although L-asparaginase related hyperglycemia is well known adverse event, it is
      not studied whether the profile of this adverse event is affected by
      intensification of L-asparaginase administration. Here, we analyzed the profile
      of L-asparaginase related hyperglycemia in a 1,176 patients with pediatric acute
      lymphoblastic leukemia treated according to the Japan Association of Childhood
      Leukemia Study ALL-02 protocol using protracted L-asparaginase administration in
      maintenance phase. We determined that a total of 75 L-asparaginase related
      hyperglycemia events occurred in 69 patients. Although 17 events (17/1176, 1.4%)
      developed in induction phase, which was lower incidence than those (10-15%) in
      previous reports, 45 events developed during the maintenance phase with
      protracted L-asparaginase administration. Multivariate analysis showed that older
      age at onset (>= 10 years) was a sole independent risk factor for L-asparaginase
      related hyperglycemia (P<0.01), especially in maintenance phase. Contrary to the
      previous reports, obesity was not associated with L-asparaginase-related
      hyperglycemia. These findings suggest that protracted administration of L
      asparaginase is the risk factor for hyperglycemia when treating adolescent and
      young adult acute lymphoblastic leukemia patients.

PMID- 26317423
TI  - GdCl3 Attenuates Schistosomiasis japonicum Egg-Induced Granulomatosis Accompanied
      by Decreased Macrophage Infiltration in Murine Liver.
AB  - Early-stage hepatic granuloma and advanced-stage fibrosis are important
      characteristics of schistosomiasis. The direct consequences of gadolinium
      chloride (GdCl3) in egg-induced granuloma formation have not been reported,
      although GdCl3 is known to block the macrophages. In present study, mice were
      infected with 15 Schistosoma japonicum (S. japonicum) cercariae and treated with
      GdCl3 (10 mg/kg body weight) twice weekly from day 21 to day 42 post-infection
      during the onset of egg-laying towards early granuloma formation. Histochemical
      staining showed that repeated injection of GdCl3 decreased macrophages
      infiltration in liver of mice infected with S. japonicum. Macrophage depletion by
      GdCl3 during the initial phase attenuated liver pathological injury characterized
      by smaller granuloma size and decreased immune inflammation as well as less
      fibrogenesis. In addition, IL-13Ralpha2 expression was reduced by GdCl3 in liver
      of mice infected with S. japonicum. The results suggest that GdCl3 depleted
      macrophages, which attenuated helminth infected immune responses involving with
      IL-13Ralpha2 signal. These findings would highlight a therapeutic potential via
      manipulating IL-13Ralpha2+ macrophage in schistosomiasis. 

PMID- 26317424
TI  - Protein Phosphatase 2A in Lipopolysaccharide-Induced Cyclooxygenase-2 Expression
      in Murine Lymphatic Endothelial Cells.
AB  - The lymphatic endothelium plays an important role in the maintenance of tissue
      fluid homeostasis. It also participates in the pathogenesis of several
      inflammatory diseases. However, little is known about the underlying mechanisms
      by which lymphatic endothelial cell responds to inflammatory stimuli. In this
      study, we explored the mechanisms by which lipopolysaccharide (LPS) induces
      cyclooxygenase (COX)-2 expression in murine lymphatic endothelial cells (SV
      LECs). LPS caused increases in cox-2 mRNA and protein levels, as well as in COX-2
      promoter luciferase activity in SV-LECs. These actions were associated with
      protein phosphatase 2A (PP2A), apoptosis signal-regulating kinase 1 (ASK1),
      JNK1/2 and p38MAPK activation, and NF-kappaB subunit p65 and C/EBPbeta
      phosphorylation. PP2A-ASK1 signaling blockade reduced LPS-induced JNK1/2,
      p38MAPK, p65 and C/EBPbeta phosphorylation. Transfection with PP2A siRNA reduced
      LPS's effects on p65 and C/EBPbeta binding to the COX-2 promoter region.
      Transfected with the NF-kappaB or C/EBPbeta site deletion of COX-2 reporter
      construct also abrogated LPS's enhancing effect on COX-2 promoter luciferase
      activity in SV-LECs. Taken together, the induction of COX-2 in SV-LECs exposed to
      LPS may involve PP2A-ASK1-JNK and/or p38MAPK-NF-kappaB and/or C/EBPbeta cascade. 

PMID- 26317425
TI  - GABA in Paraventricular Nucleus Regulates Adipose Afferent Reflex in Rats.
AB  - BACKGROUND: Chemical stimulation of white adipose tissue (WAT) induces adipose
      afferent reflex (AAR), and thereby causes a general sympathetic activation.
      Paraventricular nucleus (PVN) is important in control of sympathetic outflow.
      This study was designed to investigate the role of gamma-aminobutyric acid (GABA)
      in PVN in regulating the AAR. METHODOLOGY/PRINCIPAL FINDINGS: Experiments were
      carried out in anesthetized rats. Renal sympathetic nerve activity (RSNA) and
      mean arterial pressure (MAP) were continuously recorded. AAR was evaluated by the
      RSNA and MAP responses to electrical stimulation of the right epididymal WAT
      (eWAT) afferent nerve. Electrical stimulation of eWAT afferent nerve increase
      RSNA. Bilateral microinjection of the GABAA receptor agonist isoguvacine or the
      GABAB receptor agonist baclofen attenuated the AAR. The effect of isoguvacine on
      the AAR was greater than that of baclofen. The GABAA receptor antagonist gabazine
      enhanced the AAR, while the GABAB receptor antagonist CGP-35348 had no
      significant effect on the AAR. Bilateral PVN microinjection of vigabatrin, a
      selective GABA-transaminase inhibitor, to increase endogenous GABA levels in the
      PVN abolished the AAR. The inhibitory effect of vigabatrin on the AAR was
      attenuated by the pretreatment with gabazine or CGP-35348. Pretreatment with
      combined gabazine and CGP-35348 abolished the effects of vigabatrin. CONCLUSIONS:
      Activation of GABAA or GABAB receptors in the PVN inhibits the AAR. Blockade of
      GABAA receptors in the PVN enhances the AAR. Endogenous GABA in the PVN plays an
      important role in regulating the AAR.

PMID- 26317426
TI  - Estimating Body Composition in Adolescent Sprint Athletes: Comparison of
      Different Methods in a 3 Years Longitudinal Design.
AB  - A recommended field method to assess body composition in adolescent sprint
      athletes is currently lacking. Existing methods developed for non-athletic
      adolescents were not longitudinally validated and do not take maturation status
      into account. This longitudinal study compared two field methods, i.e., a Bio
      Impedance Analysis (BIA) and a skinfold based equation, with underwater
      densitometry to track body fat percentage relative to years from age at peak
      height velocity in adolescent sprint athletes. In this study, adolescent sprint
      athletes (34 girls, 35 boys) were measured every 6 months during 3 years (age at
      start = 14.8 +/- 1.5 yrs in girls and 14.7 +/- 1.9 yrs in boys). Body fat
      percentage was estimated in 3 different ways: 1) using BIA with the TANITA TBF
      410; 2) using a skinfold based equation; 3) using underwater densitometry which
      was considered as the reference method. Height for age since birth was used to
      estimate age at peak height velocity. Cross-sectional analyses were performed
      using repeated measures ANOVA and Pearson correlations between measurement
      methods at each occasion. Data were analyzed longitudinally using a multilevel
      cross-classified model with the PROC Mixed procedure. In boys, compared to
      underwater densitometry, the skinfold based formula revealed comparable values
      for body fatness during the study period whereas BIA showed a different pattern
      leading to an overestimation of body fatness starting from 4 years after age at
      peak height velocity. In girls, both the skinfold based formula and BIA
      overestimated body fatness across the whole range of years from peak height
      velocity. The skinfold based method appears to give an acceptable estimation of
      body composition during growth as compared to underwater densitometry in male
      adolescent sprinters. In girls, caution is warranted when interpreting
      estimations of body fatness by both BIA and a skinfold based formula since both
      methods tend to give an overestimation.

PMID- 26317427
TI  - Identification of Novel Short Ragweed Pollen Allergens Using Combined
      Transcriptomic and Immunoproteomic Approaches.
AB  - BACKGROUND: Allergy to short ragweed (Ambrosia artemisiifolia) pollen is a
      serious and expanding health problem in North America and Europe. Whereas only 10
      short ragweed pollen allergens are officially recorded, patterns of IgE
      reactivity observed in ragweed allergic patients suggest that other allergens
      contribute to allergenicity. The objective of the present study was to identify
      novel allergens following extensive characterization of the transcriptome and
      proteome of short ragweed pollen. METHODS: Following a Proteomics-Informed-by
      Transcriptomics approach, a comprehensive transcriptomic data set was built up
      from RNA-seq analysis of short ragweed pollen. Mass spectrometry-based proteomic
      analyses and IgE reactivity profiling after high resolution 2D-gel
      electrophoresis were then combined to identify novel allergens. RESULTS: Short
      ragweed pollen transcripts were assembled after deep RNA sequencing and used to
      inform proteomic analyses, thus leading to the identification of 573 proteins in
      the short ragweed pollen. Patterns of IgE reactivity of individual sera from 22
      allergic patients were assessed using an aqueous short ragweed pollen extract
      resolved over 2D-gels. Combined with information derived from the annotated
      pollen proteome, those analyses revealed the presence of multiple unreported IgE
      reactive proteins, including new Amb a 1 and Amb a 3 isoallergens as well as 7
      novel candidate allergens reacting with IgEs from 20-70% of patients. The latter
      encompass members of the carbonic anhydrase, enolase, galactose oxidase, GDP
      dissociation inhibitor, pathogenesis related-17, polygalacturonase and UDP
      glucose pyrophosphorylase families. CONCLUSIONS: We extended the list of
      allergens identified in short ragweed pollen. These findings have implications
      for both diagnosis and allergen immunotherapy purposes.

PMID- 26317428
TI  - Instant Typing Is Essential to Detect Transmission of Extended-Spectrum Beta
      Lactamase-Producing Klebsiella Species.
AB  - BACKGROUND: Infections with multidrug-resistant (MDR) microorganisms are an
      increasing threat to hospitalized patients. Although rapid typing of MDR
      microorganisms is required to apply targeted prevention measures, technical
      barriers often prevent this. We aimed to assess whether extended-spectrum beta
      lactamase (ESBL)-producing Klebsiella species are transmitted between patients
      and whether routine, rapid typing is needed. METHODS: For 43 months, the
      clonality of all ESBL-producing Klebsiella isolates from patients admitted to
      Erasmus MC University Medical Center in Rotterdam, the Netherlands was assessed
      with Raman spectroscopy. A cluster was defined as n >= 2 patients who had
      identical isolates. Primary patients were the first patients in each cluster.
      Secondary patients were those identified with an isolate clonally related to the
      isolate of the primary patient. RESULTS: Isolates from 132 patients were
      analyzed. We identified 17 clusters, with 17 primary and 56 secondary patients.
      Fifty-nine patients had a unique isolate. Patients (n = 15) in four out of the 17
      clusters were epidemiologically related. Ten of these 15 patients developed an
      infection. CONCLUSIONS: Clonal outbreaks of ESBL-producing Klebsiella species
      were detected in our hospital. Theoretically, after Raman spectroscopy had
      detected a cluster of n >= 2, six infections in secondary patients could have
      been prevented. These findings demonstrate that spread of ESBL-producing
      Klebsiella species occurs, even in a non-outbreak setting, and underscore the
      need for routine rapid typing of these MDR bacteria.

PMID- 26317429
TI  - Novel Preparation Methods of (52)Mn for ImmunoPET Imaging.
AB  - (52)Mn (t1/2 = 5.59 d, beta(+) = 29.6%, Ebetaave = 0.24 MeV) shows promise in
      positron emission tomography (PET) and in dual-modality manganese-enhanced
      magnetic resonance imaging (MEMRI) applications including neural tractography,
      stem cell tracking, and biological toxicity studies. The extension to
      bioconjugate application requires high-specific-activity (52)Mn in a state
      suitable for macromolecule labeling. To that end a (52)Mn production,
      purification, and labeling system is presented, and its applicability in
      preclinical, macromolecule PET is shown using the conjugate (52)Mn-DOTA-TRC105.
      (52)Mn is produced by 60 MUA, 16 MeV proton irradiation of natural chromium metal
      pressed into a silver disc support. Radiochemical separation proceeds by strong
      anion exchange chromatography of the dissolved Cr target, employing a semiorganic
      mobile phase, 97:3 (v:v) ethanol:HCl (11 M, aqueous). The method is 62 +/- 14%
      efficient (n = 7) in (52)Mn recovery, leading to a separation factor from Cr of
      (1.6 +/- 1.0) * 10(6) (n = 4), and an average effective specific activity of 0.8
      GBq/MUmol (n = 4) in titration against DOTA. (52)Mn-DOTA-TRC105 conjugation and
      labeling demonstrate the potential for chelation applications. In vivo images
      acquired using PET/CT in mice bearing 4T1 xenograft tumors are presented. Peak
      tumor uptake is 18.7 +/- 2.7%ID/g at 24 h post injection and ex vivo (52)Mn
      biodistribution validates the in vivo PET data. Free (52)Mn(2+) (as chloride or
      acetate) is used as a control in additional mice to evaluate the nontargeted
      biodistribution in the tumor model. 

PMID- 26317430
TI  - Immune Parameters That Distinguish Multiple Sclerosis Patients from Patients with
      Other Neurological Disorders at Presentation.
AB  - BACKGROUND/AIM: Multiple sclerosis (MS) is an inflammatory, demyelinating disease
      of the central nervous system. Effector T helper cells, mainly Th1 and Th17,
      cytotoxic T-cells, B-cells, macrophages, microglia, and the cytokines they
      secrete, are implicated in the initiation and maintenance of a deregulated immune
      response to myelin antigens and the ensuing immune-mediated demyelination. In
      this study, we investigated whether signature cytokines exist in MS patients at
      presentation to gain an insight into the underlying immunopathogenic processes at
      the early stage of the disease. METHODS: We collected serum and cerebrospinal
      fluid (CSF) samples from 123 patients at presentation, eventually diagnosed with
      MS or non-inflammatory (NIND) or inflammatory neurological diseases (IND) or
      symptomatic controls (SC). The levels of cytokines IFN-gamma, TNF-alpha, TGF
      beta1, IL-2, IL-4, IL-6, IL-10 and IL-17 were measured, and cytokine ratios, such
      as Th1/Th2, Th1/Th17, and Type-1/Type-2, were calculated. All parameters were
      tested for their correlations with the intrathecal IgG synthesis. RESULTS:
      Cytokine levels in CSF were lower than in serum in all the patients, with the
      exception of IL-6. Serum or CSF cytokine levels of MS patients did not differ
      significantly from NIND or SC, with the exception of serum IFN-gamma and TNF
      alpha that were significantly higher in NIND. IND patients presented with the
      highest levels of all cytokines in serum and CSF, with the exception of serum IL
      10 and CSF IL-17. MS patients had a significantly lower serum Th1/Th2 ratio
      compared to the NIND and IND groups, and significantly lower serum Type-1/Type-2,
      IFN-gamma/IL-10 and CSF Th1/Th17 ratios compared to IND patients. MS patients had
      a significantly higher CSF IL-17/IL-10 ratio compared to IND patients. The IgG
      index was higher in MS patients compared to the control groups; the differences
      reached statistical significance between the MS and the NIND and SC groups.
      Reiber-Felgenhauer analysis of the QIgG and QAlb indices revealed higher
      intrathecal IgG synthesis in MS patients, and higher blood-CSF barrier
      dysfunction in IND patients. The IgG index correlated with CSF IL-4 in MS
      patients only. CONCLUSIONS: We found no signature cytokines or profiles thereof
      in MS patients at presentation. Only IND patients presented with a clear Th1
      cytokine polarization in serum and CSF. The parameters that distinguished MS
      patients from patients with other neurological disorders were IgG intrathecal
      synthesis, the IgG index and its correlation with CSF IL-4 levels.

PMID- 26317431
TI  - Impact of Fishmeal Replacement in Diets for Gilthead Sea Bream (Sparus aurata) on
      the Gastrointestinal Microbiota Determined by Pyrosequencing the 16S rRNA Gene.
AB  - Recent studies have demonstrated the impact of diet on microbiota composition,
      but the essential need for the optimization of production rates and costs forces
      farms and aquaculture production to carry out continuous dietary tests. In order
      to understand the effect of total fishmeal replacement by vegetable-based feed in
      the sea bream (Sparus aurata), the microbial composition of the stomach, foregut,
      midgut and hindgut was analysed using high-throughput 16S rDNA sequencing, also
      considering parameters of growth, survival and nutrient utilisation indices.A
      total of 91,539 16S rRNA filtered-sequences were analysed, with an average number
      of 3661.56 taxonomically assigned, high-quality sequences per sample. The
      dominant phyla throughout the whole gastrointestinal tract were Actinobacteria,
      Protebacteria and Firmicutes. A lower diversity in the stomach in comparison to
      the other intestinal sections was observed. The microbial composition of the
      Recirculating Aquaculture System was totally different to that of the sea bream
      gastrointestinal tract. Total fishmeal replacement had an important impact on
      microbial profiles but not on diversity. Streptococcus (p-value: 0.043) and
      Photobacterium (p-value: 0.025) were highly represented in fish fed with fishmeal
      and vegetable-meal diets, respectively. In the stomach samples with the vegetable
      diet, reads of chloroplasts and mitochondria from vegetable dietary ingredients
      were rather abundant. Principal Coordinate Analysis showed a clear
      differentiation between diets in the microbiota present in the gut, supporting
      the presence of specific bacterial consortia associated with the diet.Although
      differences in growth and nutritive parameters were not observed, a negative
      effect of the vegetable diet on the survival rate was determined. Further studies
      are required to shed more light on the relationship between the immune system and
      sea bream gastrointestinal tract microbiota and should consider the modulation of
      the microbiota to improve the survival rate and nutritive efficacy when using
      plant-based diets. 

PMID- 26317432
TI  - Task-Driven Activity Reduces the Cortical Activity Space of the Brain: Experiment
      and Whole-Brain Modeling.
AB  - How a stimulus or a task alters the spontaneous dynamics of the brain remains a
      fundamental open question in neuroscience. One of the most robust hallmarks of
      task/stimulus-driven brain dynamics is the decrease of variability with respect
      to the spontaneous level, an effect seen across multiple experimental conditions
      and in brain signals observed at different spatiotemporal scales. Recently, it
      was observed that the trial-to-trial variability and temporal variance of
      functional magnetic resonance imaging (fMRI) signals decrease in the task-driven
      activity. Here we examined the dynamics of a large-scale model of the human
      cortex to provide a mechanistic understanding of these observations. The model
      allows computing the statistics of synaptic activity in the spontaneous condition
      and in putative tasks determined by external inputs to a given subset of brain
      regions. We demonstrated that external inputs decrease the variance, increase the
      covariances, and decrease the autocovariance of synaptic activity as a
      consequence of single node and large-scale network dynamics. Altogether, these
      changes in network statistics imply a reduction of entropy, meaning that the
      spontaneous synaptic activity outlines a larger multidimensional activity space
      than does the task-driven activity. We tested this model's prediction on fMRI
      signals from healthy humans acquired during rest and task conditions and found a
      significant decrease of entropy in the stimulus-driven activity. Altogether, our
      study proposes a mechanism for increasing the information capacity of brain
      networks by enlarging the volume of possible activity configurations at rest and
      reliably settling into a confined stimulus-driven state to allow better
      transmission of stimulus-related information. 

PMID- 26317433
TI  - Effect of crowding stress on tolerance to ischemia-reperfusion injury in young
      male and female hypertensive rats: molecular mechanisms.
AB  - Sex and social stress may represent risk factors in the etiology of hypertension
      and heart response to ischemia-reperfusion (I/R) injury. Phosphatidylinositol 3
      kinase/protein kinase B (Akt) plays an important role in the processes associated
      with hypertension and myocardial tolerance to I/R, and may be involved in
      myocardial stress reaction. The impact of chronic stress on the response to I/R
      was investigated in the hearts of 7-week-old spontaneously hypertensive (SHR) and
      Wistar-Kyoto (WKY) rats of both sexes. Stress was induced by reducing living
      space to 70 cm(2)/100 g body mass of rat for 2 weeks, while the controls were
      kept at 200 cm(2)/100 g. Langendorff-perfused hearts, subjected to I/R, exhibited
      higher vulnerability to ventricular tachycardia in crowd-stressed SHR vs. the
      control rats, and this was more pronounced in the males. Myocardial infarction
      was not affected by crowding stress in any of the groups. Male and female SHR
      showed increased activation of cardiac Akt, whereas nitric oxide synthase
      activity (NOS) with pro-apoptotic signaling decreased in the males but was not
      altered in the females (vs. WKY rats). NOS was enhanced in the female SHR and WKY
      groups by comparison with the respective males. Stress only reduced NOS activity
      in the SHR groups, and without changes in apoptotic markers. In conclusion, we
      showed that stress in young SHR mainly affects the nonlethal markers for I/R, and
      has no impact on myocardial infarction and apoptosis, despite reduced NOS
      activity. 

PMID- 26317434
TI  - Correction: Contactin-1 and Neurofascin-155/-186 Are Not Targets of Auto
      Antibodies in Multifocal Motor Neuropathy.

PMID- 26317435
TI  - Multimorbidity and Patient Safety Incidents in Primary Care: A Systematic Review
      and Meta-Analysis.
AB  - BACKGROUND: Multimorbidity is increasingly prevalent and represents a major
      challenge in primary care. Patients with multimorbidity are potentially more
      likely to experience safety incidents due to the complexity of their needs and
      frequency of their interactions with health services. However, rigorous syntheses
      of the link between patient safety incidents and multimorbidity are not
      available. This review examined the relationship between multimorbidity and
      patient safety incidents in primary care. METHODS: We followed our published
      protocol (PROSPERO registration number: CRD42014007434). Medline, Embase and
      CINAHL were searched up to May 2015. Study design and quality were assessed. Odds
      ratios (OR) and 95% confidence intervals (95% CIs) were calculated for the
      associations between multimorbidity and two categories of patient safety
      outcomes: 'active patient safety incidents' (such as adverse drug events and
      medical complications) and 'precursors of safety incidents' (such as prescription
      errors, medication non-adherence, poor quality of care and diagnostic errors).
      Meta-analyses using random effects models were undertaken. RESULTS: Eighty six
      relevant comparisons from 75 studies were included in the analysis. Meta-analysis
      demonstrated that physical-mental multimorbidity was associated with an increased
      risk for 'active patient safety incidents' (OR = 2.39, 95% CI = 1.40 to 3.38) and
      'precursors of safety incidents' (OR = 1.69, 95% CI = 1.36 to 2.03). Physical
      multimorbidity was associated with an increased risk for active safety incidents
      (OR = 1.63, 95% CI = 1.45 to 1.80) but was not associated with precursors of
      safety incidents (OR = 1.02, 95% CI = 0.90 to 1.13). Statistical heterogeneity
      was high and the methodological quality of the studies was generally low.
      CONCLUSIONS: The association between multimorbidity and patient safety is
      complex, and varies by type of multimorbidity and type of safety incident. Our
      analyses suggest that multimorbidity involving mental health may be a key driver
      of safety incidents, which has important implication for the design and targeting
      of interventions to improve safety. High quality studies examining the mechanisms
      of patient safety incidents in patients with multimorbidity are needed, with the
      goal of promoting effective service delivery and ameliorating threats to safety
      in this group of patients.

PMID- 26317437
TI  - Stay Focused! The Effects of Internal and External Focus of Attention on Movement
      Automaticity in Patients with Stroke.
AB  - Dual-task performance is often impaired after stroke. This may be resolved by
      enhancing patients' automaticity of movement. This study sets out to test the
      constrained action hypothesis, which holds that automaticity of movement is
      enhanced by triggering an external focus (on movement effects), rather than an
      internal focus (on movement execution). Thirty-nine individuals with chronic,
      unilateral stroke performed a one-leg-stepping task with both legs in single- and
      dual-task conditions. Attentional focus was manipulated with instructions. Motor
      performance (movement speed), movement automaticity (fluency of movement), and
      dual-task performance (dual-task costs) were assessed. The effects of focus on
      movement speed, single- and dual-task movement fluency, and dual-task costs were
      analysed with generalized estimating equations. Results showed that, overall,
      single-task performance was unaffected by focus (p = .341). Regarding movement
      fluency, no main effects of focus were found in single- or dual-task conditions
      (p's >= .13). However, focus by leg interactions suggested that an external focus
      reduced movement fluency of the paretic leg compared to an internal focus (single
      task conditions: p = .068; dual-task conditions: p = .084). An external focus
      also tended to result in inferior dual-task performance (beta = -2.38, p = .065).
      Finally, a near-significant interaction (beta = 2.36, p = .055) suggested that
      dual-task performance was more constrained by patients' attentional capacity in
      external focus conditions. We conclude that, compared to an internal focus, an
      external focus did not result in more automated movements in chronic stroke
      patients. Contrary to expectations, trends were found for enhanced automaticity
      with an internal focus. These findings might be due to patients' strong
      preference to use an internal focus in daily life. Future work needs to establish
      the more permanent effects of learning with different attentional foci on re
      automating motor control after stroke. 

PMID- 26317436
TI  - Serotype 1 and 8 Pneumococci Evade Sensing by Inflammasomes in Human Lung Tissue.
AB  - Streptococcus pneumoniae is a major cause of pneumonia, sepsis and meningitis.
      The pore-forming toxin pneumolysin is a key virulence factor of S. pneumoniae,
      which can be sensed by the NLRP3 inflammasome. Among the over 90 serotypes,
      serotype 1 pneumococci (particularly MLST306) have emerged across the globe as a
      major cause of invasive disease. The cause for its particularity is, however,
      incompletely understood. We therefore examined pneumococcal infection in human
      cells and a human lung organ culture system mimicking infection of the lower
      respiratory tract. We demonstrate that different pneumococcal serotypes
      differentially activate inflammasome-dependent IL-1beta production in human lung
      tissue and cells. Whereas serotype 2, 3, 6B, 9N pneumococci expressing fully
      haemolytic pneumolysins activate NLRP3 inflammasome-dependent responses, serotype
      1 and 8 strains expressing non-haemolytic toxins are poor activators of IL-1beta
      production. Accordingly, purified haemolytic pneumolysin but not serotype 1
      associated non-haemolytic toxin activates strong IL-1beta production in human
      lungs. Our data suggest that the evasion of inflammasome-dependent innate immune
      responses by serotype 1 pneumococci might contribute to their ability to cause
      invasive diseases in humans. 

PMID- 26317438
TI  - Roles of TLR/MyD88/MAPK/NF-kappaB Signaling Pathways in the Regulation of
      Phagocytosis and Proinflammatory Cytokine Expression in Response to E. faecalis
      Infection.
AB  - Enterococcus faecalis is a commensal bacterium residing in the gastrointestinal
      tract of mammals, but in certain situations it is also an opportunistic pathogen
      which can cause serious disease. Macrophages have been shown to play a critical
      role in controlling infections by commensal enterococci and also have an
      important role in mediating chromosomal instability and promoting colon cancer
      during high-level enterococcal colonization in genetically susceptible mice.
      However, the molecular mechanisms involved in the interaction of macrophages with
      enterococci during infection are not fully understood. In this study, using BMDM
      and RAW264.7 macrophages we show that enterococcal infection activates ERK, JNK
      and p38 MAPK as well as NF-kappaB, and drives polarization of macrophages towards
      the M1 phenotype. Inhibition of NF-kappaB activation significantly reduced the
      expression of TNF-alpha and IL-1beta, as did the inhibition of ERK, JNK and p38
      MAPK, although to differing extent. Enterococci-induced activation of these
      pathways and subsequent cytokine expression was contact dependent, modest
      compared to activation by E. coli and, required the adaptor protein MyD88.
      Phagocytosis of enterococci by macrophages was enhanced by preopsonization with
      E. faecalis antiserum and involved the ERK and JNK signaling pathways, with the
      adaptor protein MyD88 as an important mediator. This study of the interaction of
      macrophages with enterococci could provide a foundation for studying the
      pathogenesis of infection by this opportunistic pathogen and to developing new
      therapeutic approaches to combat enterococcal infection. 

PMID- 26317440
TI  - Gender and Children as the Moderators of the Relationship between Social Support
      and Quality of Life: An Empirical Study of People Living with HIV/AIDS in Ghana.
AB  - Although gender differences persist in the receipt of social support and the
      report of quality of life among people living with HIV/AIDS in Sub-Saharan
      Africa, the knowledge base on this topic is scant. For those living with
      HIV/AIDS, women tend to participate more than men in support group activities,
      but their gender predisposes them to lower quality of life. Therefore, this study
      seeks to determine what demographic factors moderate the relationship between
      social support and quality of life among those living with HIV/AIDS in Ghana. A
      convenience sample of 300 HIV/AIDS support group members who have experience
      participating in research studies and was obtained for use via cross-sectional
      design survey in September and October 2013. The Medical Outcome Studies (MOS)
      HIV Health Survey, the MOS Social Support Survey, and demographic questionnaire
      instruments were used to assess quality of life, social support, and demographic
      information respectively. Gender (male) F(3, 296) = 66.04, t = 2.26, p = .024)
      and having children (have children) (F(5, 294) = 40.34, t = 2.50, p = .013)
      moderated the relationship between social support and quality of life.
      Implications of the findings for practice, policy, and research in Ghana and the
      rest of the developing world were discussed. 

PMID- 26317442
TI  - On Application Of Langevin Dynamics In Logarithmic Potential To Model Ion Channel
      Gate Activity.
AB  - We model the activity of an ion channel gate by Langevin dynamics in a
      logarithmic potential. This approach enables one to describe the power-law dwell
      time distributions of the considered system, and the long-term correlations
      between the durations of the subsequent channel states, or fractal scaling of
      statistical characteristics of the gate's movement with time. Activity of an ion
      channel gate is described as an overdamped motion of the reaction coordinate in a
      confining logarithmic potential, which ensures great flexibility of the model.
      Depending on the chosen parameters, it allows one to reproduce many types of gate
      dynamics within the family of non-Markovian, anomalous conformational diffusion
      processes. In this study we apply the constructed model to largeconductance
      voltage and Ca2+-activated potassium channels (BKCa). The interpretation of model
      assumptions and parameters is provided in terms of this biological system. Our
      results show good agreement with the experimental data. 

PMID- 26317441
TI  - Local infiltration of rabies immunoglobulins without systemic intramuscular
      administration: An alternative cost effective approach for passive immunization
      against rabies.
AB  - Presently the dose of rabies immunoglobulin (RIG) which is an integral part of
      rabies post exposure prophylaxis (PEP) is calculated based on body weight though
      the recommendation is to infiltrate the wound(s). This practice demands large
      quantities of RIG which may be unaffordable to many patients. In this background,
      we conducted this study to know if the quantity and cost of RIG can be reduced by
      restricting passive immunization to local infiltration alone and avoiding
      systemic intramuscular administration based on the available scientific evidence.
      Two hundred and sixty nine category III patients bitten by suspect or confirmed
      rabid dogs/animals were infiltrated with equine rabies immunoglobulin (ERIGs) in
      and around the wound. The quantity of ERIG used was proportionate to the size and
      number of wounds irrespective of their body weight. They were followed with a
      regular course of rabies vaccination by intra-dermal route. As against 363 vials
      of RIGs required for all these cases as per current recommendation based on body
      weight, they required only 42 vials of 5ml RIG. Minimum dose of RIGs given was
      0.25 ml and maximum dose given was 8 ml. On an average 1.26 ml of RIGs was
      required per patient that costs Rs. 150 ($3). All the patients were followed for
      9 months and they were healthy and normal at the end of observation period. With
      local infiltration, that required small quantities of RIG, the RIGs could be made
      available to all patients in times of short supply in the market. A total of 30
      (11%) serum samples of patients were tested for rabies virus neutralizing
      antibodies by the rapid fluorescent focus inhibition test (RFFIT) and all showed
      antibody titers >0.5 IU/mL by day 14. In no case the dose was higher than that
      required based on body weight and no immunosuppression resulted. To conclude,
      this pilot study shows that local infiltration of RIG need to be considered in
      times of non-availability in the market or unaffordability by poor patients. This
      preliminary study needs to be done on larger scale in other centers with long
      term follow up to substantiate the results of our study.

PMID- 26317443
TI  - Epigenetic epidemiology: is there cause for optimism?

PMID- 26317444
TI  - Metabolic Syndrome in Korean Cancer Survivors and Family Members: A Study in a
      Health Promotion Center.
AB  - This cross-sectional study evaluated the risk of metabolic syndrome (MetS) in
      cancer survivors and family members. Subjects were 48,934 adults (24,786 men,
      24,148 women) aged >=40yr who receive a routine health examination at 1 hospital
      from January 2010 to December 2012. There were 2468 cancer survivors, 18,211 with
      cancer patients in the family, and 28,255 noncancer subjects, who never
      experienced cancer and whose family members either. Associations between MetS and
      cancer experience were assessed using multiple logistic regression analysis. The
      odds ratio (OR) of MetS in female cancer survivors was significantly higher than
      noncancer subjects after adjusting for age, smoking, physical activity, and
      alcohol intake (OR = 1.22, 95% confidence intervals: 1.02-1.47]. However, the OR
      of MetS for male survivors did not differ from that of noncancer subjects.
      Gastric cancer survivors had a lower OR of MetS than noncancer subjects (0.37,
      0.27-0.50). ORs of breast cancer (1.49, 1.00-2.23) and prostate cancer survivors
      (1.46, 1.07-1.99) were higher than the OR of MetS for noncancer subjects. There
      was no difference in the OR of MetS between the family members of cancer patients
      and non-cancer subjects. These findings suggest that the odds of MetS for cancer
      survivors may differ by cancer type and by sex. 

PMID- 26317446
TI  - High-Resolution Electrochemical Scanning Tunneling Microscopy (EC-STM) Flow-Cell
      Studies.
AB  - Atomic-level studies involving an electrochemical scanning tunneling microscope
      (EC-STM) flow-cell are presented. Multiple electrochemical atomic layer epitaxy
      (EC-ALE) cycles of CdTe formation were observed. For a binary compound (i.e.,
      CdTe), an EC-ALE cycle involves exposure of the substrate to a solution of the
      first precursor (CdSO4), followed by exposure to the second precursor (TeO2),
      while maintaining potential control. Interleaving blank rinses may also be used,
      but were omitted in the present studies. To allow the exchange of solutions, the
      EC-STM cell was modified to allow solution exchange via a single peristaltic
      pump. A selection valve was used to choose the solution to be introduced into the
      cell. There is evidence that the growth of the initial layer of CdTe on Au(111),
      the (?7 * ?7)-CdTe monolayer, can be improved in homogeneity and morphology by
      repeatedly depositing and stripping the Cd atomic layer. Therefore, a new
      starting cycle, which should improve the quality of deposits formed via EC-ALE,
      has been developed. 

PMID- 26317445
TI  - Diverse Genetic Array of blaCTXM-15 in Escherichia coli: A Single-Center Study
      from India.
AB  - CTX-M-15 is a chief contributor for expanded-spectrum cephalosporin and
      monobactam resistance in India, complicating treatment options. In this study, we
      have investigated genetic context of CTX-M-15 in Escherichia coli and their
      transmission dynamics in a tertiary referral hospital of India. A total of 198
      isolates were collected, of which 66 were harboring blaCTXM-15. Among them, 14
      isolates were carrying a single CTX-M-15 gene and 52 were harboring multiple
      extended-spectrum beta-lactamase genes along with blaCTX-M-15. The resistance
      gene was flanked by tnpA, ISEcp1, IS26, and ORF477 in 10 different arrangements.
      The resistance determinant was horizontally transferable through F, W, I1, and P
      Inc types of plasmids. Restriction mapping of plasmids showed a variable band
      pattern even within the same Inc types. Minimum inhibitory concentration was
      found above the breakpoint level against expanded-spectrum cephalosporins and
      monobactam while susceptible against carbapenems. blaCTX-M-15 was highly stable
      and sustained in the cell after 115 serial passages. In pulse-field gel
      electrophoresis, eight pulsotypes of E. coli were found to be responsible for the
      spread of blaCTX-M-15 in the tertiary referral center. We conclude that the
      presence of CTX-M-15 in the heterogeneous group of E. coli is highly alarming in
      terms of infection control and it may require regular monitoring, so as to
      formulate appropriate antibiotic policy to stop the spread of this resistance
      determinant. 

PMID- 26317447
TI  - Safety and Health Benefits of Novel Dietary Supplements Consisting Multiple
      Phytochemicals, Vitamins, Minerals and Essential Fatty Acids in High Fat Diet Fed
      Rats.
AB  - The objective was to determine safety and efficacy of health supplements "Beyond
      Tangy Tangerine," a multivitamin/mineral complex and combination of
      multivitamin/mineral complex, "Osteofx," a bone healthy supplement and "Ultimate
      Essential Fatty Acids" in Sprague Dawley rats consuming high-fat diets. Initially
      a pilot study was conducted which confirmed palatability and acceptability of
      supplements. In a second study, rats (n = 15/group) were randomized to Control;
      Multivitamin/mineral complex (2 g/kg BW) or Combination (2 g Multivitamin/mineral
      complex, 1.5 g Bone healthy supplement and 0.34 g Essential fatty acids/kg BW).
      No differences were observed in BW change, feed intake, organ weights or bone
      mineral composition with supplementations compared to control.
      Multivitamin/mineral complex supplementation decreased abdominal white adipose
      tissue weights (WAT) (p = .005), total (p = .033) and fat mass (p = .040), plasma
      IL-6 (p = .016) and ALKP (p = .038) and elevated plasma calcium (p < .001),
      phosphorus (p = .038), total protein (p = .002), albumin (p = .014) and globulin
      (p = .018), compared to control. Similarly, combination supplementation reduced
      WAT (p < .001), total (p = .023) and fat mass (p = .045), plasma triglycerides (p
      = .018), IL-6 (p = .002) and ALKP (p < .001) with increases in plasma calcium (p
      = .031), phosphorus (p < .001) compared to control. Results indicate that
      consuming either supplement can be considered safe and improves overall health by
      reducing inflammation, abdominal fat mass and plasma triglycerides, as well as
      promote bone health.

PMID- 26317448
TI  - Hand-assisted laparoscopic versus open partial nephrectomy in patients with T1
      renal tumor: Comparative perioperative, functional and oncological outcome.
AB  - OBJECTIVE: Studies comparing hand-assisted laparoscopic partial nephrectomy
      (HALPN) and open partial nephrectomy (OPN) for T1 kidney tumors are scarce. This
      study investigated the perioperative, functional and oncological outcomes of
      these methods. MATERIALS AND METHODS: A prospective institutional kidney tumor
      register was used to identify patients between January 2006 and May 2014
      undergoing HALPN (n = 139) or OPN (n = 165) for tumors 7 cm or smaller with non
      absolute indication for nephron-sparing surgery. The outcomes were compared using
      univariate and multivariate statistical methods. RESULTS: HALPN and OPN groups
      were similar with regard to tumor characteristics but HALPN patients were 2 years
      younger (p = 0.001) and had less comorbidity. Fewer intraoperative complications
      were encountered in HALPN than in OPN patients (7.2% vs 12.7%, p = 0.043). HALPN
      patients had less all-grade postoperative 30 day complications than OPN patients
      (27% vs 41%, p = 0.037), but there was no significant difference in Clavien 3-5
      complications. Glomerular filtration rate 3 months after operation was lower in
      the HALPN than in the OPN group (7.1 +/- 12.7% vs 10.0 +/- 12.4%, p = 0.054).
      There was no difference in overall survival or recurrence-free survival during
      the median follow-up of 35 months. CONCLUSIONS: HALPN is a feasible method to
      achieve equal perioperative, functional and oncological outcomes compared to OPN
      in patients with tumors 7 cm or smaller in diameter.

PMID- 26317449
TI  - Long-Term Ketamine Self-Injections in Major Depressive Disorder: Focus on
      Tolerance in Ketamine's Antidepressant Response and the Development of Ketamine
      Addiction.
AB  - Sub-anaesthetic ketamine is of special interest for depression research due to
      its rapid and potent but short-lived antidepressant response (after-effect). The
      presented case is the first one in the literature which deals in detail with the
      transfer from ketamine's antidepressant action to ketamine addiction. A 50-year
      old anaesthetic nurse, who had never been treated with antidepressants before,
      started with self-injecting ketamine racemate 50 mg IM once a week to cope with
      her major depression. She continuously stole ketamine from hospital stocks. Due
      to a gradually developing tolerance to ketamine's antidepressant action, she
      stepwise increased dose and frequency of ketamine self-injections up to daily 2 g
      IM (three-fold her anaesthetic dose) over six months. This was accompanied by the
      development of ketamine addiction, loss of consciousness, dissociative
      immobility, and amnesia. Inpatient detoxification treatment was characterized by
      a strong craving for ketamine and, later on, by the occurrence of a severe
      depressive episode remitting on venlafaxine. A 14-week follow-up documented a
      normal condition without any ketamine sequelae, such as craving, psychosis,
      depression, or cognitive abnormalities. Thus, awareness of ketamine addiction
      potential, even in patients who received ketamine for antidepressant purposes, is
      important. 

PMID- 26317450
TI  - Decreased Clinical Laboratory Turnaround Time After Implementation of a
      Collection Manager System.

PMID- 26317451
TI  - Rhesus Immune Globulin Dosing in the Obesity Epidemic Era.

PMID- 26317452
TI  - Assessing Clinical Laboratory Quality: A College of American Pathologists Q
      Probes Study of Prothrombin Time INR Structures, Processes, and Outcomes in 98
      Laboratories.
AB  - CONTEXT: The anticoagulant warfarin has been identified as the second most
      frequent drug responsible for serious, disabling, and fatal adverse drug events
      in the United States, and its effect on blood coagulation is monitored by the
      laboratory test called international normalized ratio (INR). OBJECTIVE: To
      determine the presence of INR policies and procedures, INR practices, and
      completeness and timeliness of reporting critical INR results in participants'
      clinical laboratories. DESIGN: Participants reviewed their INR policies and
      procedure requirements, identified their practices by using a questionnaire, and
      studied completeness of documentation and timeliness of reporting critical value
      INR results for outpatients and emergency department patients. RESULTS: In 98
      participating institutions, the 5 required policies and procedures were in place
      in 93% to 99% of clinical laboratories. Fifteen options for the allowable
      variations among duplicate results from different analyzers, 12 different
      timeliness goals for reporting critical values, and 18 unique critical value
      limits were used by participants. All required documentation elements were
      present in 94.8% of 192 reviewed INR validation reports. Critical value INR
      results were reported within the time frame established by the laboratory for
      93.4% of 2604 results, but 1.0% of results were not reported. Although the median
      laboratories successfully communicated all critical results within their
      established time frames and had all the required validation elements based in
      their 2 most recent INR calculations, those participants at the lowest 10th
      percentile were successful in 80.0% and 85.7% of these requirements,
      respectively. CONCLUSIONS: Significant opportunities exist for adherence to INR
      procedural requirements and for practice patterns and timeliness goals for INR
      critical results' reporting.

PMID- 26317453
TI  - Molecular Testing in Anatomic Pathology and Adherence to Guidelines: A College of
      American Pathologists Q-Probes Study of 2230 Testing Events Reported by 26
      Institutions.
AB  - CONTEXT: The appropriate and timely performance of molecular testing in anatomic
      pathology is an indicator of quality. The National Comprehensive Cancer Network
      (NCCN) publishes a comprehensive treatment guideline that includes
      recommendations for ancillary testing. OBJECTIVE: To establish benchmarks for
      rates of adherence to NCCN testing recommendations through a multi-institutional
      study. DESIGN: Participants in a 2013 Q-Probes study of the College of American
      Pathologists reported data from molecular testing on anatomic pathology cases,
      excluding hematolymphoid neoplasms, breast primary carcinomas, and gynecologic
      cytology. RESULTS: Twenty-six institutions reported data from 2230 molecular
      testing events. In a retrospective study limited to colon, lung, and melanoma,
      there was strict adherence to guidelines in a median 71% (10th to 90th percentile
      range, 33%-90%) and there was at least loose adherence in a median 95% (10th to
      90th percentile range, 57%-100%). There was adequate tissue to complete testing
      in a median 98% (10th to 90th percentile range, 86%-100%); in aggregate the
      adequacy rate for cell blocks was lower (84%, P < .001). Median test turnaround
      time was 8 days (10th to 90th percentile range, 4-13 days). In a prospective
      collection of all organ sites, there was strict adherence to guidelines in a
      median 53% (10th to 90th percentile range, 20%-71%), and there was at least loose
      adherence in a median 94% (10th to 90th percentile range, 75%-100%). Adherence to
      guidelines was higher for lung specimens and in institutions with more
      multidisciplinary conferences. CONCLUSIONS: This multi-institutional study
      provides benchmarking data on appropriateness and timeliness of molecular testing
      in anatomic pathology.

PMID- 26317454
TI  - Primary Anal Canal Syphilis in Men: The Clinicopathologic Spectrum of an Easily
      Overlooked Diagnosis.
AB  - CONTEXT: The incidence of syphilis is on the rise, particularly in male patients
      who are human immunodeficiency virus (HIV) positive, and men who have sex with
      men. OBJECTIVE: To describe 4 cases of primary syphilis presenting in the anal
      canal to increase awareness of its presentation and morphology in this location,
      as the diagnosis can be easily overlooked clinically and by the pathologist.
      Design .- Clinical presentation, hematoxylin-eosin-stained sections, and
      Treponema pallidum immunohistochemical staining were reviewed in detail in all 4
      cases. RESULTS: Three patients presented with anal canal ulcers; one presented
      with an ulcerated anal mass. All 4 patients were male, of whom 2 were HIV
      positive. Syphilis was clinically suspected in only 1 case; in 2 cases,
      confirmatory evaluation and treatment were prompted by pathologic diagnosis. In
      the fourth case, syphilis was diagnosed serologically at time of biopsy; however,
      the patient had an anal mass, and malignancy was clinically suspected. All 4
      cases had bandlike chronic plasma cell-rich inflammation at the squamous
      epithelium and lamina propria junction; 2 cases had poorly formed granulomas. One
      case had concomitant rectal biopsy specimens with proctitis. Treponema pallidum
      immunohistochemistry highlighted homing of organisms in a perivascular pattern
      and at the junction of squamous epithelium and lamina propria. CONCLUSIONS:
      Syphilis should be considered in the differential diagnosis of anal canal ulcers,
      anorectal inflammatory masses, and proctitis. Detailed knowledge of clinical
      history and recognition of the characteristic pattern of inflammation by the
      pathologist is important. Treponema pallidum immunohistochemical staining can
      help avoid a missed diagnosis of syphilis, which, if left unrecognized, can
      progress to late-stage disease with serious complications.

PMID- 26317455
TI  - Pathology and Laboratory Medicine Support for the American Expeditionary Forces
      by the US Army Medical Corps During World War I.
AB  - CONTEXT: Historical research on pathology and laboratory medicine services in
      World War I has been limited. In the Spanish American War, these efforts were
      primarily focused on tropical diseases. World War I problems that could be
      addressed by pathology and laboratory medicine were strikingly different because
      of the new field of clinical pathology. Geographic differences, changing war
      tactics, and trench warfare created new issues. OBJECTIVES: To describe the scope
      of pathology and laboratory medicine services in World War I and the value these
      services brought to the war effort. METHODS: Available primary and secondary
      sources related to American Expeditionary Forces' laboratory services were
      analyzed and contrasted with the British and German approaches. RESULTS: The
      United States entered the war in April 1917. Colonel Joseph Siler, MD, a career
      medical officer, was the director, and Colonel Louis B. Wilson, MD, head of
      pathology at the Mayo Clinic, was appointed assistant director of the US Army
      Medical Corps Division of Laboratories and Infectious Disease, based in Dijon,
      France. During the next year, they organized 300 efficient laboratories to
      support the American Expeditionary Forces. Autopsies were performed to better
      understand treatment of battlefield injuries, effects of chemical warfare agents,
      and the influenza pandemic; autopsies also generated teaching specimens for the
      US Army Medical Museum. Bacteriology services focused on communicable diseases.
      Laboratory testing for social diseases was very aggressive. Significant advances
      in blood transfusion techniques, which allowed brief blood storage, occurred
      during the war but were not primarily overseen by laboratory services.
      CONCLUSIONS: Both Siler and Wilson received Distinguished Service Medals.
      Wilson's vision for military pathology services helped transform American
      civilian laboratory services in the 1920s.

PMID- 26317456
TI  - Hepatosplenic T-Cell Lymphoma: A Clinicopathologic Review With an Emphasis on
      Diagnostic Differentiation From Other T-Cell/Natural Killer-Cell Neoplasms.
AB  - Hepatosplenic T-cell lymphoma is a rare, aggressive T-cell lymphoma,
      characterized by hepatosplenic sinusoidal infiltration of monotonous, medium
      sized, nonactivated cytotoxic T cells, usually of gamma/delta T-cell receptor
      type. Hepatosplenic T-cell lymphoma occurs more frequently in immunocompromised
      patients, especially in those receiving long-term immunosuppressive therapy.
      Patients usually manifest hepatosplenomegaly without lymphadenopathy. The bone
      marrow is also involved in two-thirds of cases and is often accompanied by
      circulating lymphoma cells, which, along with anemia and thrombocytopenia, may
      raise suspicion for acute leukemia. The differential diagnosis includes
      aggressive natural killer-cell leukemia, T-large granular lymphocytic leukemia, T
      lymphoblastic leukemia, enteropathy-associated T-cell lymphoma type II, primary
      cutaneous gamma/delta T-cell lymphoma, other peripheral T-cell lymphomas,
      myelodysplastic syndrome, and infectious mononucleosis. The diagnosis is usually
      established from the combination of clinical findings, histologic features, and
      immunophenotype, although cytogenetic/molecular studies are occasionally needed.
      Hepatosplenic T-cell lymphoma exhibits a dismal clinical course with a poor
      response to currently available therapies. 

PMID- 26317457
TI  - A Brief Review and Update of the Clinicopathologic Diagnosis of Arrhythmogenic
      Cardiomyopathy.
AB  - Arrhythmogenic cardiomyopathy (AC) has traditionally been regarded as a rare
      disease with variably penetrant autosomal-dominant inheritance. Recent years have
      revealed that AC is actually a spectrum of disease with prevalence much higher
      than previously thought. Diagnosis can be quite challenging because of highly
      variable clinical presentation, even among family members sharing a mutation.
      Unlike other cardiomyopathies, AC has a concealed phase during which patients
      have arrhythmias in the absence of structural heart disease but remain at risk of
      sudden cardiac death. Importantly, it is in the setting of sudden cardiac death
      that pathologists are most likely to encounter AC. It is critical that these
      findings not be overlooked, as family members of the deceased may also be
      affected and could potentially avoid such a dismal outcome. With time, advances
      in ancillary studies are likely to expand the role for pathologists in AC
      diagnosis. 

PMID- 26317458
TI  - Blended Learning Improves Science Education.
AB  - Blended learning is an emerging paradigm for science education but has not been
      rigorously assessed. We performed a randomized controlled trial of blended
      learning. We found that in-class problem solving improved exam performance, and
      video assignments increased attendance and satisfaction. This validates a new
      model for science communication and education. 

PMID- 26317459
TI  - PD-1 Blockers.
AB  - Nivolumab and pembrolizumab are monoclonal antibodies that block the programmed
      death-1 receptor (PD-1, CD279), resulting in dis-inhibition of tumor-specific
      immune responses. Both are recently approved for use in the treatment of
      metastatic melanoma, and nivolumab as well for non-small cell lung cancer. 

PMID- 26317460
TI  - DNA Methylation Inhibitors in Cancer Therapy: The Immunity Dimension.
AB  - DNA demethylating agents are approved for some blood malignancies and are under
      active investigation in solid tumors, but how these drugs work has remained
      unclear. In this issue of Cell, two groups show that these agents activate a
      toxic cellular antiviral program through transcriptional activation of endogenous
      retroviral sequences. 

PMID- 26317461
TI  - Gateway Arch to the RNA Exosome.
AB  - The RNA exosome degrades many different RNAs. Thoms et al. now fill an important
      gap in our understanding of how the exosome recognizes distinct subsets of target
      RNAs. 

PMID- 26317462
TI  - A Long-Distance Chromatin Affair.
AB  - Changes in transcription factor binding sequences result in correlated changes in
      chromatin composition locally and at sites hundreds of kilobases away. New
      studies demonstrate that this concordance is mediated via spatial chromatin
      interactions that constitute regulatory modules of the human genome. 

PMID- 26317463
TI  - Not All DDRs Are Created Equal: Non-Canonical DNA Damage Responses.
AB  - It is commonly assumed that there is a single canonical DNA damage response (DDR)
      that protects cells from various types of double-strand breaks and that its
      activation occurs via recognition of DNA ends by the DDR machinery. Recent work
      suggests that both assumptions may be oversimplifications. Here, we discuss
      several variations of the DDR in which the pathway is activated by diverse
      cellular events and/or generates distinct signaling outcomes. The existence of
      multiple non-canonical DDRs provides insights into how DNA damage is sensed and
      suggests a highly modular organization of the DDR. 

PMID- 26317465
TI  - DNA-Demethylating Agents Target Colorectal Cancer Cells by Inducing Viral Mimicry
      by Endogenous Transcripts.
AB  - DNA-demethylating agents have shown clinical anti-tumor efficacy via an unknown
      mechanism of action. Using a combination of experimental and bioinformatics
      analyses in colorectal cancer cells, we demonstrate that low-dose 5-AZA-CdR
      targets colorectal cancer-initiating cells (CICs) by inducing viral mimicry. This
      is associated with induction of dsRNAs derived at least in part from endogenous
      retroviral elements, activation of the MDA5/MAVS RNA recognition pathway, and
      downstream activation of IRF7. Indeed, disruption of virus recognition pathways,
      by individually knocking down MDA5, MAVS, or IRF7, inhibits the ability of 5-AZA
      CdR to target colorectal CICs and significantly decreases 5-AZA-CdR long-term
      growth effects. Moreover, transfection of dsRNA into CICs can mimic the effects
      of 5-AZA-CdR. Together, our results represent a major shift in understanding the
      anti-tumor mechanisms of DNA-demethylating agents and highlight the
      MDA5/MAVS/IRF7 pathway as a potentially druggable target against CICs. 

PMID- 26317464
TI  - Architectural and Functional Commonalities between Enhancers and Promoters.
AB  - With the explosion of genome-wide studies of regulated transcription, it has
      become clear that traditional definitions of enhancers and promoters need to be
      revisited. These control elements can now be characterized in terms of their
      local and regional architecture, their regulatory components, including histone
      modifications and associated binding factors, and their functional contribution
      to transcription. This Review discusses unifying themes between promoters and
      enhancers in transcriptional regulatory mechanisms. 

PMID- 26317466
TI  - Inhibiting DNA Methylation Causes an Interferon Response in Cancer via dsRNA
      Including Endogenous Retroviruses.
AB  - We show that DNA methyltransferase inhibitors (DNMTis) upregulate immune
      signaling in cancer through the viral defense pathway. In ovarian cancer (OC),
      DNMTis trigger cytosolic sensing of double-stranded RNA (dsRNA) causing a type I
      interferon response and apoptosis. Knocking down dsRNA sensors TLR3 and MAVS
      reduces this response 2-fold and blocking interferon beta or its receptor
      abrogates it. Upregulation of hypermethylated endogenous retrovirus (ERV) genes
      accompanies the response and ERV overexpression activates the response. Basal
      levels of ERV and viral defense gene expression significantly correlate in
      primary OC and the latter signature separates primary samples for multiple tumor
      types from The Cancer Genome Atlas into low versus high expression groups. In
      melanoma patients treated with an immune checkpoint therapy, high viral defense
      signature expression in tumors significantly associates with durable clinical
      response and DNMTi treatment sensitizes to anti-CTLA4 therapy in a pre-clinical
      melanoma model. 

PMID- 26317467
TI  - Viral and Cellular Genomes Activate Distinct DNA Damage Responses.
AB  - In response to cellular genome breaks, MRE11/RAD50/NBS1 (MRN) activates a global
      ATM DNA damage response (DDR) that prevents cellular replication. Here, we show
      that MRN-ATM also has critical functions in defending the cell against DNA
      viruses. We reveal temporally distinct responses to adenovirus genomes: a
      critical MRN-ATM DDR that must be inactivated by E1B-55K/E4-ORF3 viral
      oncoproteins and a global MRN-independent ATM DDR to viral nuclear domains that
      does not impact viral replication. We show that MRN binds to adenovirus genomes
      and activates a localized ATM response that specifically prevents viral DNA
      replication. In contrast to chromosomal breaks, ATM activation is not amplified
      by H2AX across megabases of chromatin to induce global signaling and replicative
      arrest. Thus, gammaH2AX foci discriminate "self" and "non-self" genomes and
      determine whether a localized anti-viral or global ATM response is appropriate.
      This provides an elegant mechanism to neutralize viral genomes without
      jeopardizing cellular viability. 

PMID- 26317468
TI  - The Nuclear Pore-Associated TREX-2 Complex Employs Mediator to Regulate Gene
      Expression.
AB  - Nuclear pore complexes (NPCs) influence gene expression besides their established
      function in nuclear transport. The TREX-2 complex localizes to the NPC basket and
      affects gene-NPC interactions, transcription, and mRNA export. How TREX-2
      regulates the gene expression machinery is unknown. Here, we show that TREX-2
      interacts with the Mediator complex, an essential regulator of RNA Polymerase
      (Pol) II. Structural and biochemical studies identify a conserved region on TREX
      2, which directly binds the Mediator Med31/Med7N submodule. TREX-2 regulates
      assembly of Mediator with the Cdk8 kinase and is required for recruitment and
      site-specific phosphorylation of Pol II. Transcriptome and phenotypic profiling
      confirm that TREX-2 and Med31 are functionally interdependent at specific genes.
      TREX-2 additionally uses its Mediator-interacting surface to regulate mRNA export
      suggesting a mechanism for coupling transcription initiation and early steps of
      mRNA processing. Our data provide mechanistic insight into how an NPC-associated
      adaptor complex accesses the core transcription machinery. 

PMID- 26317469
TI  - The Exosome Is Recruited to RNA Substrates through Specific Adaptor Proteins.
AB  - The exosome regulates the processing, degradation, and surveillance of a plethora
      of RNA species. However, little is known about how the exosome recognizes and is
      recruited to its diverse substrates. We report the identification of adaptor
      proteins that recruit the exosome-associated helicase, Mtr4, to unique RNA
      substrates. Nop53, the yeast homolog of the tumor suppressor PICT1, targets Mtr4
      to pre-ribosomal particles for exosome-mediated processing, while a second
      adaptor Utp18 recruits Mtr4 to cleaved rRNA fragments destined for degradation by
      the exosome. Both Nop53 and Utp18 contain the same consensus motif, through which
      they dock to the "arch" domain of Mtr4 and target it to specific substrates.
      These findings show that the exosome employs a general mechanism of recruitment
      to defined substrates and that this process is regulated through adaptor
      proteins. 

PMID- 26317470
TI  - A Liquid-to-Solid Phase Transition of the ALS Protein FUS Accelerated by Disease
      Mutation.
AB  - Many proteins contain disordered regions of low-sequence complexity, which cause
      aging-associated diseases because they are prone to aggregate. Here, we study
      FUS, a prion-like protein containing intrinsically disordered domains associated
      with the neurodegenerative disease ALS. We show that, in cells, FUS forms liquid
      compartments at sites of DNA damage and in the cytoplasm upon stress. We confirm
      this by reconstituting liquid FUS compartments in vitro. Using an in vitro
      "aging" experiment, we demonstrate that liquid droplets of FUS protein convert
      with time from a liquid to an aggregated state, and this conversion is
      accelerated by patient-derived mutations. We conclude that the physiological role
      of FUS requires forming dynamic liquid-like compartments. We propose that liquid
      like compartments carry the trade-off between functionality and risk of
      aggregation and that aberrant phase transitions within liquid-like compartments
      lie at the heart of ALS and, presumably, other age-related diseases.

PMID- 26317471
TI  - A Distinct Function of Regulatory T Cells in Tissue Protection.
AB  - Regulatory T (Treg) cells suppress immune responses to a broad range of non
      microbial and microbial antigens and indirectly limit immune inflammation
      inflicted tissue damage by employing multiple mechanisms of suppression. Here, we
      demonstrate that selective Treg cell deficiency in amphiregulin leads to severe
      acute lung damage and decreased blood oxygen concentration during influenza virus
      infection without any measureable alterations in Treg cell suppressor function,
      antiviral immune responses, or viral load. This tissue repair modality is
      mobilized in Treg cells in response to inflammatory mediator IL-18 or alarmin IL
      33, but not by TCR signaling that is required for suppressor function. These
      results suggest that, during infectious lung injury, Treg cells have a major
      direct and non-redundant role in tissue repair and maintenance-distinct from
      their role in suppression of immune responses and inflammation-and that these two
      essential Treg cell functions are invoked by separable cues. 

PMID- 26317472
TI  - TMEM175 Is an Organelle K(+) Channel Regulating Lysosomal Function.
AB  - Potassium is the most abundant ion to face both plasma and organelle membranes.
      Extensive research over the past seven decades has characterized how K(+)
      permeates the plasma membrane to control fundamental processes such as secretion,
      neuronal communication, and heartbeat. However, how K(+) permeates organelles
      such as lysosomes and endosomes is unknown. Here, we directly recorded organelle
      K(+) conductance and discovered a major K(+)-selective channel KEL on endosomes
      and lysosomes. KEL is formed by TMEM175, a protein with unknown function. Unlike
      any of the ~80 plasma membrane K(+) channels, TMEM175 has two repeats of 6
      transmembrane-spanning segments and has no GYG K(+) channel sequence signature
      containing, pore-forming P loop. Lysosomes lacking TMEM175 exhibit no K(+)
      conductance, have a markedly depolarized DeltaPsi and little sensitivity to
      changes in [K(+)], and have compromised luminal pH stability and abnormal fusion
      with autophagosomes during autophagy. Thus, TMEM175 comprises a K(+) channel that
      underlies the molecular mechanism of lysosomal K(+) permeability. 

PMID- 26317473
TI  - Crystal Structure of Staphylococcus aureus Cas9.
AB  - The RNA-guided DNA endonuclease Cas9 cleaves double-stranded DNA targets with a
      protospacer adjacent motif (PAM) and complementarity to the guide RNA. Recently,
      we harnessed Staphylococcus aureus Cas9 (SaCas9), which is significantly smaller
      than Streptococcus pyogenes Cas9 (SpCas9), to facilitate efficient in vivo genome
      editing. Here, we report the crystal structures of SaCas9 in complex with a
      single guide RNA (sgRNA) and its double-stranded DNA targets, containing the 5'
      TTGAAT-3' PAM and the 5'-TTGGGT-3' PAM, at 2.6 and 2.7 A resolutions,
      respectively. The structures revealed the mechanism of the relaxed recognition of
      the 5'-NNGRRT-3' PAM by SaCas9. A structural comparison of SaCas9 with SpCas9
      highlighted both structural conservation and divergence, explaining their
      distinct PAM specificities and orthologous sgRNA recognition. Finally, we applied
      the structural information about this minimal Cas9 to rationally design compact
      transcriptional activators and inducible nucleases, to further expand the CRISPR
      Cas9 genome editing toolbox. 

PMID- 26317474
TI  - Slit and Receptor Tyrosine Phosphatase 69D Confer Spatial Specificity to Axon
      Branching via Dscam1.
AB  - Axonal branching contributes substantially to neuronal circuit complexity.
      Studies in Drosophila have shown that loss of Dscam1 receptor diversity can fully
      block axon branching in mechanosensory neurons. Here we report that cell
      autonomous loss of the receptor tyrosine phosphatase 69D (RPTP69D) and loss of
      midline-localized Slit inhibit formation of specific axon collaterals through
      modulation of Dscam1 activity. Genetic and biochemical data support a model in
      which direct binding of Slit to Dscam1 enhances the interaction of Dscam1 with
      RPTP69D, stimulating Dscam1 dephosphorylation. Single-growth-cone imaging reveals
      that Slit/RPTP69D are not required for general branch initiation but instead
      promote the extension of specific axon collaterals. Hence, although regulation of
      intrinsic Dscam1-Dscam1 isoform interactions is essential for formation of all
      mechanosensory-axon branches, the local ligand-induced alterations of Dscam1
      phosphorylation in distinct growth-cone compartments enable the spatial
      specificity of axon collateral formation. 

PMID- 26317476
TI  - SnapShot: Astrocytes in Health and Disease.
AB  - Astrocytes are central nervous system (CNS) glial cells with many important
      functions for normal development and neural functioning. They help control
      extracellular ion and neurotransmitter concentrations; provide neurotrophic
      support; are implicated in synapse formation, function, and pruning; and help
      maintain the blood-brain barrier. Following injury and in disease, they undergo
      rapid and chronic alterations in function that can either promote or hinder
      recovery, depending on the disease. 

PMID- 26317475
TI  - Central Cholinergic Neurons Are Rapidly Recruited by Reinforcement Feedback.
AB  - Basal forebrain cholinergic neurons constitute a major neuromodulatory system
      implicated in normal cognition and neurodegenerative dementias. Cholinergic
      projections densely innervate neocortex, releasing acetylcholine to regulate
      arousal, attention, and learning. However, their precise behavioral function is
      poorly understood because identified cholinergic neurons have never been recorded
      during behavior. To determine which aspects of cognition their activity might
      support, we recorded cholinergic neurons using optogenetic identification in mice
      performing an auditory detection task requiring sustained attention. We found
      that a non-cholinergic basal forebrain population-but not cholinergic neurons
      were correlated with trial-to-trial measures of attention. Surprisingly,
      cholinergic neurons responded to reward and punishment with unusual speed and
      precision (18 +/- 3 ms). Cholinergic responses were scaled by the unexpectedness
      of reinforcement and were highly similar across neurons and two nuclei
      innervating distinct cortical areas. These results reveal that the cholinergic
      system broadcasts a rapid and precisely timed reinforcement signal, supporting
      fast cortical activation and plasticity. 

PMID- 26317477
TI  - Propofol facilitates excitatory inputs of cerebellar Purkinje cells by depressing
      molecular layer interneuron activity during sensory information processing in
      vivo in mice.
AB  - Propofol is a rapid-acting sedative-hypnotic medication that has been widely used
      for the induction and maintenance of anesthesia; it has specific actions on
      different areas of the brain, such as sensory information transmission in the
      somatosensory cortex. However, the effects of propofol on the properties of
      sensory stimulation-evoked responses in cerebellar Purkinje cells (PCs) are
      currently unclear. In the present study, we studied the effects of propofol on
      facial stimulation-evoked responses in cerebellar PCs and molecular level
      interneurons (MLIs) in urethane-anesthetized mice using electrophysiological and
      pharmacological methods. Our results showed that cerebellar surface perfusion
      with propofol induced a decrease in the amplitude of the gamma-aminobutyric acid
      (GABA)-ergic component (P1) in a dose-dependent manner, but induced a significant
      increase in the amplitude of the excitatory response (N1). The IC50 of propofol
      induced inhibition of P1 was 217.3 MUM. In contrast, propofol (100 MUM) depressed
      the spontaneous activity and tactile-evoked responses in MLIs. In addition,
      blocking GABA(A) receptor activity abolished the propofol (300 MUM)-induced
      inhibition of the tactile-evoked inhibitory response and the increase in the
      sensory stimulation-evoked spike firing rate of PCs. These results indicated that
      propofol depressed the tactile stimulation-evoked spike firing of MLIs, resulting
      in a decrease in the amplitude of the tactile-evoked inhibitory response and an
      increase in the amplitude of the excitatory response in the cerebellar PCs of
      mice. Our results suggest that propofol modulates sensory information processing
      in cerebellar cortical PCs and MLIs through the activation of GABA(A) receptors.

PMID- 26317478
TI  - Altered cognitive processes in the acute phase of mTBI: an analysis of
      independent components of event-related potentials.
AB  - Mild traumatic brain injuries (mTBI) generate acute disruptions of brain function
      and a subset of patients shows persisting cognitive, affective, and somatic
      symptoms. Deficits in the executive function domain are among the more frequent
      cognitive impairments reported by mTBI patients. By means of independent
      component analysis, event-related potential components from a visual cued go/nogo
      task, namely contingent negative variation (CNV) and NoGo-P3, were decomposed
      into distinct independent components that have been shown to be associated with
      the executive processes of energization, monitoring, and task setting. A group of
      symptomatic mTBI patients was compared with a group of controls matched for sex,
      age, and education. Patients showed reduced amplitudes in the late CNV as well as
      in the early NoGo-P3 subcomponents. Whereas the decreased CNVlate component
      indicates an impaired ability to generate representations of stimulus-response
      associations and to energize the maintenance of response patterns, the reduced
      P3NOGOearly component suggests a deficient ability to invest attentional effort
      in the initiation of response patterns in mTBI patients. Besides indicating the
      effects of mTBI on cognitive brain processing, the results may open up the
      possibility for assessing individual mTBI profiles and facilitate personalized
      rehabilitative measures. 

PMID- 26317479
TI  - Comparison of Mydriatic Provocative and Dark Room Prone Provocative Tests for
      Anterior Chamber Angle Configuration.
AB  - PURPOSE: To investigate the relationship between angle configuration and
      diagnostic provocation tests such as the mydriatic provocative test (MPT) and the
      dark room prone provocative test (DRPPT). MATERIALS AND METHODS: Seventy eyes of
      70 consecutive patients with primary angle closure suspect, primary angle
      closure, or primary angle closure glaucoma were included. The anterior chamber
      depth, angle opening distance 500, trabecular-iris space area 500, and iris
      thickness (IT) were quantitatively determined by anterior segment optical
      coherence tomography, and the MPT and DRPPT were used to investigate intraocular
      pressure variations. RESULTS: Seven eyes were positive and 3 eyes were suspected
      positive, using the MPT, whereas 10 eyes were positive and 7 eyes were suspected
      positive using the DRPPT. The anterior chamber depth and angle opening distance
      500 of the positive and suspected positive groups (positive group), using the
      MPT, were significantly less than those of the negative group (P=0.013, P=0.013,
      respectively). IT of the positive group, using the MPT, was significantly greater
      than the negative group, using the same test (P=0.003). The trabecular-iris space
      area 500 of the positive group was significantly less than the negative group,
      using both the MPT (P<0.001) and the DRPPT (P=0.004). CONCLUSIONS: Eyes from the
      positive group, using the MPT, contained a shallower anterior chamber, narrower
      angle, and greater IT than those from the negative group. These results suggested
      that the MPT results better correlated with the anterior chamber angle
      configuration in eyes with primary angle closure, than the results using the
      DRPPT.

PMID- 26317480
TI  - Outcomes of Bleb Revision With Mitomycin C After Ex-PRESS Shunt Surgery.
AB  - PURPOSE: Investigate efficacy and safety of bleb revision using mitomycin C after
      Ex-PRESS shunt surgery. PATIENTS AND METHODS: We performed chart reviews of 36
      consecutive eyes from 34 patients with previous Ex-PRESS shunt surgery who
      underwent subsequent bleb revision with mitomycin C. The mean follow-up time was
      13.5 months. The primary outcome measure was surgical success. Secondary outcomes
      included visual acuity, intraocular pressure, number of medications, and
      complications. RESULTS: Twenty-four eyes had open-angle glaucoma (61.1%). Mean
      time from Ex-PRESS to bleb revision was 8.8 months. Complete success rate for the
      immediate 3-month postoperative period was 94.4% and qualified success rate was
      97.2%. Complete and qualified success rates for the entire follow-up period were
      40% and 65.7%, respectively. Visual acuity remained stable throughout the study
      period, and at 1 year, average intraocular pressure was 14.7 mm Hg on an average
      of 1.7 medications. No major complications were reported. CONCLUSIONS: Bleb
      revision in eyes with an Ex-PRESS shunt is a safe and efficacious procedure. The
      surgical outcomes are within the range of published outcomes for bleb needling
      after trabeculectomy. Further research with larger sample size and longer follow
      up is needed to confirm these results.

PMID- 26317481
TI  - The Effect of Cumulative Dissipated Energy on Changes in Intraocular Pressure
      After Uncomplicated Cataract Surgery by Phacoemulsification.
AB  - PURPOSE: To investigate the association between ultrasound energy, expressed as
      cumulative dissipated energy (CDE), and changes in intraocular pressure (IOP)
      after uncomplicated cataract surgery by phacoemulsification. METHODS: In this
      prospective study, nonglaucomatous subjects underwent cataract surgery by
      phacoemulsification. IOP was compared by clustered linear regression at 4
      separate time-points: preoperative, 1 day, 1 month, and 3 months after cataract
      surgery. Changes in the IOP were evaluated as a function of CDE using univariate
      and multivariate clustered linear regression models, which adjusted for sex,
      ethnicity, age, axial length, spherical equivalent, mean preoperative Shaffer
      gonioscopy grade of all 4 quadrants, cataract grade, preoperative IOP, central
      corneal thickness, and use of both eyes in the same subject. RESULTS: One hundred
      sixty-one eyes (89 Asian, 49 white, 12 African, and 11 Hispanic) from 116
      nonglaucomatous subjects were analyzed. The 161 eyes included 81 right and 80
      left eyes. The 89 Asian eyes included 46 Chinese, 35 Filipino, and 8 Vietnamese.
      Preoperative IOP was 14.9+/-3.2 mm Hg. Postoperative IOP significantly increased
      to 16.0+/-4.9 mm Hg at 1 day (P=0.037) and decreased to 12.4+/-3.1 and 12.3+/-3.0
      mm Hg at 1 and 3 months, respectively (both P<0.0001). IOP changes at 1 day, 1
      month, and 3 months did not demonstrate significant associations with CDE
      measurements in either univariate or multivariate clustered linear regression
      analyses (all P>0.05). CONCLUSIONS: The amount of ultrasound energy delivered to
      the eye during phacoemulsification, expressed as CDE, was not associated with
      postoperative changes in IOP.

PMID- 26317482
TI  - Why Patients With Glaucoma Lose Vision: The Patient Perspective.
AB  - PURPOSE: To explore why glaucoma patients believe that glaucoma continues to
      cause vision loss despite the availability of effective treatment. METHODS: Nine
      focus groups were conducted in 3 geographically and ethnically diverse areas of
      the United States (Los Angeles, CA; Rochester, MN; Durham, NC) that included 56
      participants, 31 with poor vision and 25 with good vision. Content analysis was
      used to identify important themes. Semiquantitative analysis was used to measure
      the frequency of each theme. RESULTS: A total of 474 relevant comments were made
      in the 9 focus groups. Focus groups elicited 305 comments about barriers to
      glaucoma management including issues with adherence (30%), the doctor-patient
      relationship (21%), knowledge about glaucoma (19%), personal support systems
      (19%), and barriers to health care delivery such as cost and insurance (11%). A
      total of 101 comments were made regarding feelings about glaucoma and 58 comments
      were made regarding beliefs about disease and treatment. CONCLUSIONS: These focus
      groups brought up many issues surrounding barriers to glaucoma treatment,
      perceived susceptibility to glaucoma, perceived benefits to treatment, and the
      emotional response to living with glaucoma. There is a need to create a more
      comprehensive chronic disease management approach for patients with glaucoma to
      address both the concrete and emotional issues identified in these focus group
      discussions.

PMID- 26317483
TI  - Vitamin A Palmitate and Carbomer Gel Protects the Conjunctiva of Patients With
      Long-term Prostaglandin Analogs Application.
AB  - PURPOSE: To investigate the protective effects of vitamin A palmitate and
      carbomer gel on the morphology of conjunctival epithelium and density of goblet
      cells (GCs) in patients on long-term prostaglandin analogs (PGAs) application.
      METHODS: In this prospective cohort study, 23 primary open-angle glaucoma
      patients and 7 normal-tension glaucoma patients prescribed PGAs for >1 year were
      enrolled into 3 identical clinical trials and randomized into 3 groups (10 per
      group). Patients were treated twice daily with vitamin A palmitate eye gel 0.1%,
      or carbomer eye gel 0.2%, or no additional application of these 2 drugs. Ocular
      surface disease index questionnaires, Schirmer 1 test without anesthesia, tear
      break-up time test, and GCs density assessment by in vivo confocal microscopy and
      conjunctival impression cytology analysis were performed at baseline and at
      months 1, 3, and 6 of the study. RESULTS: Both vitamin A palmitate and carbomer
      gel led to a significant improvement in ocular surface disease index
      questionnaires score and prevented the gradual decline in tear break-up time.
      Vitamin A palmitate significantly increased the GC density after treatment. The
      GC density assessed by in vivo confocal microscopy positively correlated with
      that measured by conjunctival impression cytology. CONCLUSIONS: Vitamin A
      palmitate and carbomer eye gel can effectively relieve dry eye symptom caused by
      long-term application of PGAs by increasing the GCs density and thereby reducing
      the toxicity to the conjunctiva. Vitamin A palmitate and carbomer eye gel may be
      valuable alternatives for glaucoma patients who prescribed long-term PGAs.

PMID- 26317484
TI  - The usefulness of fQRS and QRS distortion for predicting reperfusion success and
      infarct-related artery patency in patients who underwent thrombolytic therapy.
AB  - BACKGROUND: The aim of this study is to determine whether the presence of
      fragmented QRS (fQRS) and QRS distortion on admission ECG can be used to predict
      the success of treatment before beginning thrombolytic therapy (TT). PATIENTS AND
      METHODS: Two hundred and three eligible patients with acute ST elevation
      myocardial infarction who received TT consecutively between 1 January 2009 and 1
      July 2013 were enrolled. The presence of fQRS and QRS distortion was analyzed at
      admission ECG. The electrocardiographic criteria of reperfusion were defined as
      50% or more of ST resolution (STR), whereas the angiographic criteria of
      reperfusion were defined as thrombolysis in myocardial infarction 2/3 flow in the
      infarct-related artery. RESULTS: fQRS was detected in 63 (31%) patients. Compared
      with patients with non-fQRS, STR was lower (46.1+/-17.7 vs. 73.6+/-20.9,
      respectively; P<0.001), thrombolysis failure was higher (44.4 vs. 9.3%,
      respectively; P<0.001), and thrombolysis in myocardial infarction 0/1 flow was
      more common (39.7 vs. 10.7%, respectively; P<0.001) in patients with fQRS. Higher
      numbers of fQRS derivations were significantly related to low percentages of STR
      (r=-0.615, P<0.001). In predicting occluded infarct-related artery, we found no
      difference between the negative predictive values of fQRS and inadequate STR
      after TT (89.3 vs. 95.1%; P>0.05). However, there was no relationship between QRS
      distortion and failed thrombolysis. CONCLUSION: fQRS was detected in just 31% of
      the patients, but we found that it can be used to predict thrombolytic failure.
      Patients who have this simple marker on admission ECG may be directed to
      percutaneous interventions as a first-line therapy without any delay.

PMID- 26317485
TI  - Theoretical Spectroscopic Characterization at Low Temperatures of Dimethyl
      Sulfoxide: The Role of Anharmonicity.
AB  - The structural and spectroscopic parameters of dimethyl sulfoxide (DMSO) are
      predicted from CCSD(T)-F12 calculations that can help to resolve the outstanding
      problem of the rovibrational spectroscopy. DMSO is a near oblate top that
      presents a trigonal pyramidal geometry. Rotational parameters are determined at
      the equilibrium and in selected vibrational states. For the ground state, the
      rotational constants were calculated to be A0 = 7031.7237 MHz, B0 = 6920.1221
      MHz, and C0 = 4223.3389 MHz, at few megahertz from the previous experimental
      measurements. Ab initio calculations allow us to assert that DMSO rotational
      constants are strongly dependent on anharmonic effects. Asymmetry increases with
      the vibrational energy. Harmonic frequencies, torsional parameters, and a two
      dimensional potential energy surface (2D-PES) focused to describe the internal
      rotation of the two methyl groups are determined at the CCSD(T)-F12 level of
      theory. For the medium and small amplitude motions, anharmonic effects are
      estimated with MP2 theory getting an excellent agreement with experimental data
      for the nu11 and nu23 fundamentals. Torsional energies and transitions are
      computed variationally form the 2D-PES that denotes strong interactions between
      both internal tops. The vibrationally corrected V3 torsional barrier is evaluated
      to be 965.32 cm(-1). The torsional splitting of the ground vibrational state has
      been estimated to be lower than 0.01 cm(-1). Although the nu13 torsional
      fundamental is found at 229.837 cm(-1) in good agreement with previous
      assessment, there is not accord for the low intense transition nu24. A new
      assignment predicting nu24 to lie between 190 and 195 cm(-1) is proposed. 

PMID- 26317486
TI  - Electroencephalographic markers of robot-aided therapy in stroke patients for the
      evaluation of upper limb rehabilitation.
AB  - Stroke is the leading cause of permanent disability in developed countries; its
      effects may include sensory, motor, and cognitive impairment as well as a reduced
      ability to perform self-care and participate in social and community activities.
      A number of studies have shown that the use of robotic systems in upper limb
      motor rehabilitation programs provides safe and intensive treatment to patients
      with motor impairments because of a neurological injury. Furthermore, robot-aided
      therapy was shown to be well accepted and tolerated by all patients; however, it
      is not known whether a specific robot-aided rehabilitation can induce beneficial
      cortical plasticity in stroke patients. Here, we present a procedure to study
      neural underpinning of robot-aided upper limb rehabilitation in stroke patients.
      Neurophysiological recordings use the following: (a) 10-20 system
      electroencephalographic (EEG) electrode montage; (b) bipolar vertical and
      horizontal electrooculographies; and (c) bipolar electromyography from the
      operating upper limb. Behavior monitoring includes the following: (a) clinical
      data and (b) kinematic and dynamic of the operant upper limb movements.
      Experimental conditions include the following: (a) resting state eyes closed and
      eyes open, and (b) robotic rehabilitation task (maximum 80 s each block to reach
      4-min EEG data; interblock pause of 1 min). The data collection is performed
      before and after a program of 30 daily rehabilitation sessions. EEG markers
      include the following: (a) EEG power density in the eyes-closed condition; (b)
      reactivity of EEG power density to eyes opening; and (c) reactivity of EEG power
      density to robotic rehabilitation task. The above procedure was tested on a
      subacute patient (29 poststroke days) and on a chronic patient (21 poststroke
      months). After the rehabilitation program, we observed (a) improved clinical
      condition; (b) improved performance during the robotic task; (c) reduced delta
      rhythms (1-4 Hz) and increased alpha rhythms (8-12 Hz) during the resting state
      eyes-closed condition; (d) increased alpha desynchronization to eyes opening; and
      (e) decreased alpha desynchronization during the robotic rehabilitation task. We
      conclude that the present procedure is suitable for evaluation of the neural
      underpinning of robot-aided upper limb rehabilitation. 

PMID- 26317487
TI  - Presentation and Outcomes of C4d-Negative Antibody-Mediated Rejection After
      Kidney Transplantation.
AB  - The updated Banff classification allows for the diagnosis of antibody-mediated
      rejection (AMR) in the absence of peritubular capillary C4d staining. Our
      objective was to quantify allograft loss risk in patients with consistently C4d
      negative AMR (n = 51) compared with C4d-positive AMR patients (n = 156) and
      matched control subjects without AMR. All first-year posttransplant biopsy
      results from January 2004 through June 2014 were reviewed and correlated with the
      presence of donor-specific antibody (DSA). C4d-negative AMR patients were not
      different from C4d-positive AMR patients on any baseline characteristics,
      including immunologic risk factors (panel reactive antibody, prior transplant,
      HLA mismatch, donor type, DSA class, and anti-HLA/ABO-incompatibility). C4d
      positive AMR patients were significantly more likely to have a clinical
      presentation (85.3% vs. 54.9%, p < 0.001), and those patients presented
      substantially earlier posttransplantation (median 14 [interquartile range 8-32]
      days vs. 46 [interquartile range 20-191], p < 0.001) and were three times more
      common (7.8% vs 2.5%). One- and 2-year post-AMR-defining biopsy graft survival in
      C4d-negative AMR patients was 93.4% and 90.2% versus 86.8% and 82.6% in C4d
      positive AMR patients, respectively (p = 0.4). C4d-negative AMR was associated
      with a 2.56-fold (95% confidence interval, 1.08-6.05, p = 0.033) increased risk
      of graft loss compared with AMR-free matched controls. No clinical
      characteristics were identified that reliably distinguished C4d-negative from C4d
      positive AMR. However, both phenotypes are associated with increased graft loss
      and thus warrant consideration for intervention. 

PMID- 26317488
TI  - Effects of Different End-Point Cooking Temperatures on the Efficiency of
      Encapsulated Phosphates on Lipid Oxidation Inhibition in Ground Meat.
AB  - Effects of 0.5% encapsulated (e) phosphates (sodium tripolyphosphate, STP; sodium
      hexametaphosphate, HMP; sodium pyrophosphate, SPP) on lipid oxidation during
      storage (0, 1, and 7 d) of ground meat (chicken, beef) after being cooked to 3
      end-point cooking temperatures (EPCT; 71, 74, and 77  degrees C) were evaluated.
      The use of STP or eSTP resulted in lower (P < 0.05) cooking loss (CL) compared to
      encapsulated or unencapsulated forms of HMP and SPP. Increasing EPCT led to a
      significant increase in CL (P < 0.05). Both STP and eSTP increased pH, whereas
      SPP and eSPP decreased pH (P < 0.05). The higher orthophosphate (OP) was obtained
      with STP or SPP compared to their encapsulated counterparts (P < 0.05). The
      lowest OP was determined in samples with HMP or eHMP (P < 0.05). A 77  degrees C
      EPCT resulted in lower OP in chicken compared to 74 and 71  degrees C (P < 0.05),
      dissimilar to beef, where EPCT did not affect OP. In encapsulated or
      unencapsulated form, using STP and SPP enhanced reduction in TBARS and lipid
      hydroperoxides (LPO) compared with HMP (P < 0.05). Regardless of the phosphate
      type, more effective lipid oxidation inhibition was achieved by the use of
      encapsulated forms (P < 0.05). Increasing EPCT resulted in lower TBARS in beef
      and higher LPO values in both beef and chicken samples (P < 0.05). Findings
      suggest that encapsulated phosphates can be a strategy to inhibit lipid oxidation
      for meat industry and the efficiency of encapsulated phosphates on lipid
      oxidation inhibition can be enhanced by lowering EPCT. 

PMID- 26317489
TI  - Elevated concentration of cytokines in aqueous in post-vitrectomy eyes.
AB  - BACKGROUND: We aim to study the level of inflammatory cytokines in aqueous of
      post-vitrectomy eyes. METHODS: Aqueous samples were obtained from post-vitrectomy
      eyes that underwent cataract surgery. Samples from age-related cataract patients
      were also collected as controls. The concentrations of cytokines were measured by
      array-based multiplex sandwich enzyme-linked immunosorbent assay system and
      microparticle-based multiplex cytokine assay. RESULTS: Eighteen post-vitrectomy
      eyes from 18 patients were included; all received one vitrectomy with gas
      injection for rhegmatogenous retinal detachment. The mean interval between
      vitrectomy and cataract surgery was 22.33 months (range 6 to 80). Primary results
      show that in post-vitrectomy eyes the levels of many cytokines, such as B
      lymphocyte chemo-attractant, I-309, interleukin (IL)-6, IL-8, interferon gamma
      induced protein-10 and intercellular adhesion molecule 1, were higher than
      control. Further analysis demonstrated that the levels of IL-8, interferon gamma
      induced protein-10 and intercellular adhesion molecule 1 were significantly
      elevated in post-vitrectomy eyes, even after the subjects were divided by their
      refractive state. CONCLUSIONS: The concentrations of some cytokines were
      increased in the anterior chambers of post-vitrectomy eyes even a long time after
      vitreous surgery. This surge in post-operative cytokines might cause changing in
      the micro-environment of the anterior, and this might contribute to the
      development of secondary glaucoma or fasten the development of cataract in these
      eyes.

PMID- 26317491
TI  - Early-Onset Severe Preeclampsia by First Trimester Pregnancy-Associated Plasma
      Protein A and Total Human Chorionic Gonadotropin (Podcast).

PMID- 26317492
TI  - An Optimal Free Energy Dissipation Strategy of the MinCDE Oscillator in
      Regulating Symmetric Bacterial Cell Division.
AB  - Sustained molecular oscillations are ubiquitous in biology. The obtained
      oscillatory patterns provide vital functions as timekeepers, pacemakers and
      spacemarkers. Models based on control theory have been introduced to explain how
      specific oscillatory behaviors stem from protein interaction feedbacks, whereas
      the energy dissipation through the oscillating processes and its role in the
      regulatory function remain unexplored. Here we developed a general framework to
      assess an oscillator's regulation performance at different dissipation levels.
      Using the Escherichia coli MinCDE oscillator as a model system, we showed that a
      sufficient amount of energy dissipation is needed to switch on the oscillation,
      which is tightly coupled to the system's regulatory performance. Once the
      dissipation level is beyond this threshold, unlike stationary regulators'
      monotonic performance-to-cost relation, excess dissipation at certain steps in
      the oscillating process damages the oscillator's regulatory performance. We
      further discovered that the chemical free energy from ATP hydrolysis has to be
      strategically assigned to the MinE-aided MinD release and the MinD immobilization
      steps for optimal performance, and a higher energy budget improves the robustness
      of the oscillator. These results unfold a novel mode by which living systems
      trade energy for regulatory function. 

PMID- 26317490
TI  - Human papillomavirus capsids preferentially bind and infect tumor cells.
AB  - We previously determined that human papillomavirus (HPV) virus-like particles
      (VLPs) and pseudovirions (PsV) did not, respectively, bind to or infect intact
      epithelium of the cervicovaginal tract. However, they strongly bound heparan
      sulfate proteoglycans (HSPG) on the basement membrane of disrupted epithelium and
      infected the keratinocytes that subsequently entered the disrupted site. We here
      report that HPV capsids (VLP and PsV) have the same restricted tropism for a wide
      variety of disrupted epithelial and mesothelial tissues, whereas intact tissues
      remain resistant to binding. However, the HPV capsids directly bind and infect
      most tumor-derived cell lines in vitro and have analogous tumor-specific
      properties in vivo, after local or intravenous injection, using orthotopic models
      for human ovarian and lung cancer, respectively. The pseudovirions also
      specifically infected implanted primary human ovarian tumors. Heparin and iota
      carrageenan blocked binding and infection of all tumor lines tested, implying
      that tumor cell binding is HSPG-dependent. A survey using a panel of modified
      heparins indicates that N-sulfation and, to a lesser degree, O-6 sulfation of the
      surface HSPG on the tumors are important for HPV binding. Therefore, it appears
      that tumor cells consistently evolve HSPG modification patterns that mimic the
      pattern normally found on the basement membrane but not on the apical surfaces of
      normal epithelial or mesothelial cells. Consequently, appropriately modified HPV
      VLPs and/or PsV could be useful reagents to detect and potentially treat a
      remarkably broad spectrum of cancers. 

PMID- 26317493
TI  - Nutritional analysis and microbiological evaluation of commercially available
      enteral diets for cats.
AB  - OBJECTIVE: To determine the prevalence of nutrients less than or greater than
      accepted standards in commercially available enteral diets for cats, and to
      identify contamination incidence in enteral diets for cats. DESIGN: Prospective
      cross-sectional study. SETTING: University teaching hospital. SAMPLES: Seven
      commercial enteral diets for cats. INTERVENTIONS: Labels were evaluated to
      determine if diets were intended to be nutritionally complete and balanced. One
      diet under storage techniques partially representative of clinical conditions was
      sampled on days 0, 1, 3, 5, and 7 of storage for aerobic bacterial culture.
      MEASUREMENTS AND MAIN RESULTS: All 7 diets were analyzed for key nutrients and
      results were compared to Association of American Feed Control Officials (AAFCO)
      Nutrient Profiles for Adult Cats for maintenance and National Research Council
      recommended allowance (NRC-RA). From label information, 4 diets were classified
      as complete and balanced and 3 diets were classified as not complete and
      balanced. All 7 diets had at least 1 nutrient less than the AAFCO minimums and
      the NRC-RA. The total number of nutrients less than AAFCO minimums ranged from 3
      to 9 (median = 4), with iron, potassium, and manganese being the most common.
      Concentrations of some nutrients were undetectable. None of the samples tested
      had a positive aerobic culture at baseline (day 0) or on subsequent samples from
      days 1, 3, 5, and 7 under any storage condition. CONCLUSIONS: None of the diets
      analyzed met all of the minimum nutrient concentrations. While short-term feeding
      may not be of concern for an individual patient, clinicians should be aware of
      potential nutritional limitations when feeding enteral diets to ill or injured
      cats.

PMID- 26317494
TI  - An accurate and inexpensive color-based assay for detecting severe anemia in a
      limited-resource setting.
AB  - Severe anemia is an important cause of morbidity and mortality among children in
      resource-poor settings, but laboratory diagnostics are often limited in these
      locations. To address this need, we developed a simple, inexpensive, and color
      based point-of-care (POC) assay to detect severe anemia. The purpose of this
      study was to evaluate the accuracy of this novel POC assay to detect moderate and
      severe anemia in a limited-resource setting. The study was a cross-sectional
      study conducted on children with sickle cell anemia in Luanda, Angola. The
      hemoglobin concentrations obtained by the POC assay were compared to reference
      values measured by a calibrated automated hematology analyzer. A total of 86
      samples were analyzed (mean hemoglobin concentration 6.6 g/dL). There was a
      strong correlation between the hemoglobin concentrations obtained by the POC
      assay and reference values obtained from an automated hematology analyzer
      (r=0.88, P<0.0001). The POC assay demonstrated excellent reproducibility (r=0.93,
      P<0.0001) and the reagents appeared to be durable in a tropical setting (r=0.93,
      P<0.0001). For the detection of severe anemia that may require blood transfusion
      (hemoglobin <5 g/dL), the POC assay had sensitivity of 88.9% and specificity of
      98.7%. These data demonstrate that an inexpensive (<$0.25 USD) POC assay
      accurately estimates low hemoglobin concentrations and has the potential to
      become a transformational diagnostic tool for severe anemia in limited-resource
      settings.

PMID- 26317495
TI  - Application of high-throughput mini-bioreactor system for systematic scale-down
      modeling, process characterization, and control strategy development.
AB  - High-throughput systems and processes have typically been targeted for process
      development and optimization in the bioprocessing industry. For process
      characterization, bench scale bioreactors have been the system of choice. Due to
      the need for performing different process conditions for multiple process
      parameters, the process characterization studies typically span several months
      and are considered time and resource intensive. In this study, we have shown the
      application of a high-throughput mini-bioreactor system viz. the Advanced
      Microscale Bioreactor (ambr15(TM) ), to perform process characterization in less
      than a month and develop an input control strategy. As a pre-requisite to process
      characterization, a scale-down model was first developed in the ambr system (15
      mL) using statistical multivariate analysis techniques that showed comparability
      with both manufacturing scale (15,000 L) and bench scale (5 L). Volumetric sparge
      rates were matched between ambr and manufacturing scale, and the ambr process
      matched the pCO2 profiles as well as several other process and product quality
      parameters. The scale-down model was used to perform the process characterization
      DoE study and product quality results were generated. Upon comparison with DoE
      data from the bench scale bioreactors, similar effects of process parameters on
      process yield and product quality were identified between the two systems. We
      used the ambr data for setting action limits for the critical controlled
      parameters (CCPs), which were comparable to those from bench scale bioreactor
      data. In other words, the current work shows that the ambr15(TM) system is
      capable of replacing the bench scale bioreactor system for routine process
      development and process characterization.

PMID- 26317496
TI  - Receptor-Mediated Liposome Fusion Kinetics at Aqueous/Liquid Crystal Interfaces.
AB  - Membrane fusion events are essential to cell biology, and a number of
      reductionist systems have been developed to mimic the behavior of these
      biological motifs. One such system monitors the DNA hybridization-mediated fusion
      of liposomes with the liquid crystal (LC) interface by observing changes in LC
      orientation using a simple optical detection scheme. We have systematically
      explored key parameters of this system to determine their effects on individual
      elementary steps of the complex fusion mechanism. The liposome composition,
      specifically the degree of lipid unsaturation and PE content, decreased the
      bilayer rigidity, thereby increasing the rate of vesicle rupture under the stress
      applied by DNA hybridization. In contrast, the presence of cholesterol had the
      opposite effect on the mechanical properties of the bilayer, and hence of the
      membrane fusion rates. The accessibility of receptor moieties (i.e.,
      complementary DNA oligonucleotides) affected the fusion kinetics by modulating
      the rate of hybridization events. DNA accessibility was controlled by systematic
      variation of the length of the DNA receptor molecules and the thickness of the
      steric barrier comprised of adsorbed PEGylated lipids. These results provide
      design rules for understanding the trade-offs between response kinetics and other
      important system properties, such as nonspecific adsorption. Moreover, these
      findings improve our understanding of the biophysical properties of membrane
      fusion, an important process in both natural and model systems used for bioassay
      and bioimaging applications. 

PMID- 26317497
TI  - Difference in Outcomes between First-Operated vs. Fellow-Operated Eyes in
      Patients Undergoing Bilateral Trabeculectomies.
AB  - MAIN OBJECTIVE: To compare the course and outcome of first- and fellow-operated
      eyes in patients who underwent bilateral trabeculectomies and to investigate the
      factors associated with the difference. METHODS: Preoperative characteristics,
      including the interval between surgeries, were compared between the first- and
      fellow-operated eyes in 42 patients who underwent bilateral trabeculectomies.
      Postoperative intraocular pressure and bleb vascularity, using postoperative
      anterior segment photos, were compared at various time points between the first-
      and fellow-operated eyes. Surgical success was evaluated at 1 year after surgery
      and at the final follow-up. Factors affecting the difference between the first
      and fellow eyes were analyzed. RESULTS: There was no significant difference in
      success or failure rates at 1 year postoperatively and at the final follow-up
      between the first- and fellow-operated eyes. Early postoperative IOP and the
      degree of bleb vascularity were higher in the fellow-operated eyes (P = 0.001 and
      0.003, respectively at week 1 postoperative). The difference in IOP between the
      first- and fellow-operated eyes was greater in patients whose interval between
      surgeries was shorter than 3 weeks (P = 0.026). CONCLUSIONS: In patients
      undergoing bilateral trabeculectomies, early postoperative IOP was higher in the
      fellow-operated eyes than the first-operated eyes; the difference was greater
      when the interval between surgeries was shorter. The first-operated eye may
      influence the early postoperative inflammatory response in the fellow-operated
      eye. Our findings have clinical implications for planning treatment of patients
      who may need bilateral surgery.

PMID- 26317498
TI  - Study of Surface Charge Instabilities by EOF Measurements on a Chip: A Real-Time
      Hysteresis and Peptide Adsorption Based Methodology.
AB  - This paper describes the measurement of the electroosmotic mobility (EOF) in a
      Wheatstone fluidic bridge (MUFWB) as a direct probe of the surface instability.
      The variation of EOF known as one major contribution of the electrokinetic
      migration has been determined with a real-time measurement platform after
      different conditionings on chips. We also scan the pH of the background
      electrolytes with three different ionic strengths to evaluate the dependencies of
      the EOF as a function of the pH. A hysteresis methodology has been developed for
      probing the surface charge instabilities. EOF mobility has been recorded during
      on-a-chip electrophoresis to estimate the effect of such instability on the
      analytical performance. As expected, our experimental curves show that a decrease
      in the ionic strength increases the surface charge stability of the hybrid
      microchip. This result demonstrates that ionic exchanges between the surface and
      the fluid are clearly involved in the stability of the surface charge. With this
      original method based on real-time EOF measurement, the surface state can be
      characterized after hydrodynamic and electrophoresis sequences to mimic any
      liquid conditioning and separation steps. Finally, as a demonstrative
      application, isotherms of the adsorption of insulin have been recorded showing
      the change in surface charge by unspecific adsorption of this biomolecule onto
      the microfluidic channel's wall. These methodologies and findings could be
      particularly relevant to investigating various analytical pathways and to
      understanding the molecular mechanisms at solid/liquid interfaces. 

PMID- 26317499
TI  - Suppression of Adaptive Immune Cell Activation Does Not Alter Innate Immune
      Adipose Inflammation or Insulin Resistance in Obesity.
AB  - Obesity-induced inflammation in visceral adipose tissue (VAT) is a major
      contributor to insulin resistance and type 2 diabetes. Whereas innate immune
      cells, notably macrophages, contribute to visceral adipose tissue (VAT)
      inflammation and insulin resistance, the role of adaptive immunity is less well
      defined. To address this critical gap, we used a model in which endogenous
      activation of T cells was suppressed in obese mice by blocking MyD88-mediated
      maturation of CD11c+ antigen-presenting cells. VAT CD11c+ cells from
      Cd11cCre+Myd88fl/fl vs. control Myd88fl/fl mice were defective in activating T
      cells in vitro, and VAT T and B cell activation was markedly reduced in
      Cd11cCre+Myd88fl/fl obese mice. However, neither macrophage-mediated VAT
      inflammation nor systemic inflammation were altered in Cd11cCre+Myd88fl/fl mice,
      thereby enabling a focused analysis on adaptive immunity. Unexpectedly, fasting
      blood glucose, plasma insulin, and the glucose response to glucose and insulin
      were completely unaltered in Cd11cCre+Myd88fl/fl vs. control obese mice. Thus,
      CD11c+ cells activate VAT T and B cells in obese mice, but suppression of this
      process does not have a discernible effect on macrophage-mediated VAT
      inflammation or systemic glucose homeostasis. 

PMID- 26317502
TI  - HybridDock: A Hybrid Protein-Ligand Docking Protocol Integrating Protein- and
      Ligand-Based Approaches.
AB  - Structure-based molecular docking and ligand-based similarity search are two
      commonly used computational methods in computer-aided drug design. Structure
      based docking tries to utilize the structural information on a drug target like
      protein, and ligand-based screening takes advantage of the information on known
      ligands for a target. Given their different advantages, it would be desirable to
      use both protein- and ligand-based approaches in drug discovery when information
      for both the protein and known ligands is available. Here, we have presented a
      general hybrid docking protocol, referred to as HybridDock, to utilize both the
      protein structures and known ligands by combining the molecular docking program
      MDock and the ligand-based similarity search method SHAFTS, and evaluated our
      hybrid docking protocol on the CSAR 2013 and 2014 exercises. The results showed
      that overall our hybrid docking protocol significantly improved the performance
      in both binding affinity and binding mode predictions, compared to the sole MDock
      program. The efficacy of the hybrid docking protocol was further confirmed using
      the combination of DOCK and SHAFTS, suggesting an alternative docking approach
      for modern drug design/discovery.

PMID- 26317501
TI  - Targeting the Sonic Hedgehog-Gli1 Pathway as a Potential New Therapeutic Strategy
      for Myelodysplastic Syndromes.
AB  - The complex mechanistic array underlying the pathogenesis of myelodysplastic
      syndrome (MDS) is still unclear. Although dysregulations of different signaling
      pathways involved in MDS have been described, the identification of specific
      biomarkers and therapy targets remains an important task in order to establish
      novel therapeutic approaches. Here, we demonstrated that the Shh signaling
      pathway is active in MDS and correlated it with disease progression.
      Additionally, the knockdown of Gli1 significantly inhibited cell proliferation in
      vitro and in vivo. Gli1 silencing also induced apoptosis and G0/G1 phase arrest.
      Furthermore, Gli1 silencing enhanced the demethylating effect of 5-aza-2'
      deoxycytidine on the p15 gene promoter and subsequently promoted its expression
      by inhibiting DNA methyltransferase 1(DNMT1). Our findings show that the Shh
      signaling pathway plays a role in the pathogenesis and disease progression of
      MDS, and proceeds by modulating DNA methylation. This pathway may prove to be a
      potential therapeutic target for enhancing the therapeutic effects of 5
      azacytidine on malignant transformation of MDS. 

PMID- 26317500
TI  - The Activation of Phytophthora Effector Avr3b by Plant Cyclophilin is Required
      for the Nudix Hydrolase Activity of Avr3b.
AB  - Plant pathogens secrete an arsenal of effector proteins to impair host immunity.
      Some effectors possess enzymatic activities that can modify their host targets.
      Previously, we demonstrated that a Phytophthora sojae RXLR effector Avr3b acts as
      a Nudix hydrolase when expressed in planta; and this enzymatic activity is
      required for full virulence of P. sojae strain P6497 in soybean (Glycine max).
      Interestingly, recombinant Avr3b produced by E. coli does not have the hydrolase
      activity unless it was incubated with plant protein extracts. Here, we report the
      activation of Avr3b by a prolyl-peptidyl isomerase (PPIase), cyclophilin, in
      plant cells. Avr3b directly interacts with soybean cyclophilin GmCYP1, which
      activates the hydrolase activity of Avr3b in a PPIase activity-dependent manner.
      Avr3b contains a putative Glycine-Proline (GP) motif; which is known to confer
      cyclophilin-binding in other protein substrates. Substitution of the Proline
      (P132) in the putative GP motif impaired the interaction of Avr3b with GmCYP1; as
      a result, the mutant Avr3bP132A can no longer be activated by GmCYP1, and is also
      unable to promote Phytophthora infection. Avr3b elicits hypersensitive response
      (HR) in soybean cultivars producing the resistance protein Rps3b, but Avr3bP132A
      lost its ability to trigger HR. Furthermore, silencing of GmCYP1 rendered reduced
      cell death triggered by Avr3b, suggesting that GmCYP1-mediated Avr3b maturation
      is also required for Rps3b recognition. Finally, cyclophilins of Nicotiana
      benthamiana can also interact with Avr3b and activate its enzymatic activity.
      Overall, our results demonstrate that cyclophilin is a "helper" that activates
      the enzymatic activity of Avr3b after it is delivered into plant cells; as such,
      cyclophilin is required for the avirulence and virulence functions of Avr3b. 

PMID- 26317503
TI  - Selection criteria for resection in hepatocellular carcinoma: Can we expand them?

PMID- 26317504
TI  - Asymmetric Electrophilic alpha-Amination of Silyl Enol Ether Derivatives via the
      Nitrosocarbonyl Hetero-ene Reaction.
AB  - The first example of a general asymmetric nitrosocarbonyl hetero-ene reaction is
      described. The procedure uses a copper-catalyzed aerobic oxidation of a
      commercially available chiral nitrosocarbonyl precursor (EleNOr) and is
      operationally simple. The transformation is both high yielding and highly
      diastereoselective for a range of silyl enol ether derivatives. A variety of
      synthetically useful postfunctionalization reactions are presented along with a
      mechanistic rationale that can be used as a predictive model for future
      asymmetric reactions with nitrosocarbonyl intermediates. 

PMID- 26317505
TI  - Farmers' Preference for Rice Traits: Insights from Farm Surveys in Central Luzon,
      Philippines, 1966-2012.
AB  - Many modern rice varieties (MVs) have been released but only a few have been
      widely adopted by farmers. To understand farmers' preferences, we characterized
      MVs released in the Philippines from 1966 to 2013 and identified important
      characteristics of the varieties that were widely adopted in Central Luzon using
      farm surveys conducted in 1966-2012. We found that farmers adopt MVs that are
      high yielding, mature faster, and have long and slender grains, high milling
      recovery, and intermediate amylose content. The amylose content of adopted
      varieties has been declining, suggesting value in developing softer rice. To have
      a high potential for adoption, new MVs should have characteristics within the
      ranges of values observed for the adopted MVs. In addition, new MVs should have
      higher head rice recovery, less chalky grains, and better resistance to pests and
      diseases. Most MVs released in 2005-2013 compared poorly in these three traits.
      To reduce the risk of severe outbreaks, broad spectrum resistance should be
      incorporated into new MVs. This analysis of five decades of farm surveys provides
      insights into the varietal characteristics preferred by farmers which could
      contribute to the establishment of a product profile for developing improved MVs
      that are more targeted and, hence, would have high potential for adoption by
      farmers in Central Luzon and similar areas. We recommend a similar analysis be
      done in other major rice growing regions to aid the development of MVs that are
      more responsive to farmers' needs and preferences. 

PMID- 26317506
TI  - A novel route for the removal of bodily heavy metal lead (II).
AB  - The lead ion concentration in bile is considerably higher than in blood, and bile
      is released into the alimentary tract. Thiol-modified SBA-15 administered orally
      can combine with lead ions in the alimentary tract. In this paper, the in vitro
      lead absorption of bile was investigated. This thiol-modified SBA-15 material was
      used in pharmacodynamics studies on rabbits. The result that the lead content in
      faeces was notably higher indicates that thiol-modified SBA-15 can efficiently
      remove lead. The mechanism could include the following: thiol-modified SBA-15
      material cuts off the heavy metal lead recirculation in the process of bile
      enterohepatic circulation by chelating the lead in the alimentary tract, causing
      a certain proportion of lead to be removed by the thiol mesoporous material, and
      the lead is subsequently egested out of the body in faeces. The results indicate
      that this material might be a potential non-injection material for the removal
      bodily heavy metal lead in the alimentary tract. This material may also be a
      useful means of lead removal, especially for non-acute sub-poisoning symptoms. 

PMID- 26317507
TI  - PhosphoPath: Visualization of Phosphosite-centric Dynamics in Temporal Molecular
      Networks.
AB  - Protein phosphorylation is an essential post-translational modification (PTM)
      regulating many biological processes at the cellular and multicellular level.
      Continuous improvements in phosphoproteomics technology allow the analysis of
      this PTM in an expanding biological content, yet up until now proteome data
      visualization tools are still very gene centric, hampering the ability to
      comprehensively map and study PTM dynamics. Here we present PhosphoPath, a
      Cytoscape app designed for the visualization and analysis of quantitative
      proteome and phosphoproteome data sets. PhosphoPath brings knowledge into the
      biological network by importing publically available data and enables PTM site
      specific visualization of information from quantitative time series. To showcase
      PhosphoPath performance we use a quantitative proteomics data set comparing
      patient-derived melanoma cell lines grown in either conventional cell culture or
      xenografts. 

PMID- 26317508
TI  - Enhanced Removal of Hexavalent Chromium in the Presence of H2O2 in Frozen Aqueous
      Solutions.
AB  - The reductive transformation of Cr(VI) to Cr(III) by H2O2 in ice was compared
      with that in water. The reduction of Cr(VI) was significant at -20  degrees C
      (ice), whereas the reduction efficiency was very low at 25  degrees C (water).
      This enhanced reduction of Cr(VI) in ice was observed over a wide range of H2O2
      concentration (20-1000 MUM), pH (3-11), and freezing temperature (-10 to -30 
      degrees C). The observed molar ratio of consumed [H2O2] to reduced [Cr(VI)] in
      ice was in close agreement with the theoretical (stoichiometric) molar ratio
      (1.5) for H2O2-mediated Cr(VI) reduction through proton-coupled electron transfer
      (PCET). The synergistic increase in Cr(VI) reduction in water by increasing the
      H2O2 and proton concentrations confirms that the freeze concentration of both
      H2O2 and protons in the liquid brine is primarily responsible for the enhanced
      Cr(VI) reduction in ice. In comparison, the one-electron reduction of Cr(VI) to
      Cr(V) and subsequent reoxidation of Cr(V) to Cr(VI) is the major reaction
      mechanism in aqueous solution. The reduction efficiency of Cr(VI) by H2O2 in the
      frozen aqueous electroplating wastewater was similar to that in the frozen
      aqueous deionized water, which verifies the enhanced reduction of Cr(VI) by
      freezing in real Cr(VI)-contaminated aquatic systems. 

PMID- 26317510
TI  - Effect of Paying for Performance on Utilisation, Quality, and User Costs of
      Health Services in Tanzania: A Controlled Before and After Study.
AB  - BACKGROUND: Despite widespread implementation across Africa, there is limited
      evidence of the effect of payment for performance (P4P) schemes in low income
      countries on the coverage of quality services and affordability, consistent with
      universal health coverage objectives. We examined the effect of a government P4P
      scheme on utilisation, quality, and user costs of health services in Tanzania.
      METHODS: We evaluated the effects of a P4P scheme on utilisation of all maternal
      and child immunization services targeted by the scheme, and non-targeted general
      outpatient service use. We also evaluated effects on patient satisfaction with
      care and clinical content of antenatal care, and user costs. The evaluation was
      done in 150 facilities across all 7 intervention districts and 4 comparison
      districts with two rounds of data collection over 13-months in January 2012 and
      February 2013. We sampled 3000 households of women who had delivered in the 12
      months prior to interview; 1500 patients attending health facilities for targeted
      and non-targeted services at each round of data collection. Difference-in
      difference regression analysis was employed. FINDINGS: We estimated a significant
      positive effect on two out of eight targeted indicators. There was an 8.2% (95%
      CI: 3.6% to 12.8%) increase in coverage of institutional deliveries among women
      in the intervention area, and a 10.3% (95% CI: 4.4% to 16.1%) increase in the
      provision of anti-malarials during pregnancy. Use of non-targeted services
      reduced at dispensaries by 57.5 visits per month among children under five (95%
      CI: -110.2 to -4.9) and by 90.8 visits per month for those aged over five (95%
      CI: -156.5 to -25.2). There was no evidence of an effect of P4P on patient
      experience of care for targeted services. There was a 0.05 (95% CI: 0.01 to 0.10)
      increase in the patient satisfaction score for non-targeted services. P4P was
      associated with a 5.0% reduction in those paying out of pocket for deliveries
      (95% CI: -9.3% to -0.7%) but there was no evidence of an effect on the average
      amount paid. CONCLUSION: This study adds to the very limited evidence on the
      effects of P4P at scale and highlights the potential risks of such schemes in
      relation to non-targeted service use. Further consideration of the design of P4P
      schemes is required to enhance progress towards universal health coverage, and
      close monitoring of effects on non-targeted services and user costs should be
      encouraged.

PMID- 26317509
TI  - DNA-Launched Alphavirus Replicons Encoding a Fusion of Mycobacterial Antigens Acr
      and Ag85B Are Immunogenic and Protective in a Murine Model of TB Infection.
AB  - There is an urgent need for effective prophylactic measures against Mycobacterium
      tuberculosis (Mtb) infection, particularly given the highly variable efficacy of
      Bacille Calmette-Guerin (BCG), the only licensed vaccine against tuberculosis
      (TB). Most studies indicate that cell-mediated immune responses involving both
      CD4+ and CD8+ T cells are necessary for effective immunity against Mtb. Genetic
      vaccination induces humoral and cellular immune responses, including CD4+ and
      CD8+ T-cell responses, against a variety of bacterial, viral, parasitic and tumor
      antigens, and this strategy may therefore hold promise for the development of
      more effective TB vaccines. Novel formulations and delivery strategies to improve
      the immunogenicity of DNA-based vaccines have recently been evaluated, and have
      shown varying degrees of success. In the present study, we evaluated DNA-launched
      Venezuelan equine encephalitis replicons (Vrep) encoding a novel fusion of the
      mycobacterial antigens alpha-crystallin (Acr) and antigen 85B (Ag85B), termed
      Vrep-Acr/Ag85B, for their immunogenicity and protective efficacy in a murine
      model of pulmonary TB. Vrep-Acr/Ag85B generated antigen-specific CD4+ and CD8+ T
      cell responses that persisted for at least 10 wk post-immunization.
      Interestingly, parenterally administered Vrep-Acr/Ag85B also induced T cell
      responses in the lung tissues, the primary site of infection, and inhibited
      bacterial growth in both the lungs and spleens following aerosol challenge with
      Mtb. DNA-launched Vrep may, therefore, represent an effective approach to the
      development of gene-based vaccines against TB, particularly as components of
      heterologous prime-boost strategies or as BCG boosters.

PMID- 26317512
TI  - Predicting Extreme Droughts in Savannah Africa: A Comparison of Proxy and Direct
      Measures in Detecting Biomass Fluctuations, Trends and Their Causes.
AB  - We monitored pasture biomass on 20 permanent plots over 35 years to gauge the
      reliability of rainfall and NDVI as proxy measures of forage shortfalls in a
      savannah ecosystem. Both proxies are reliable indicators of pasture biomass at
      the onset of dry periods but fail to predict shortfalls in prolonged dry spells.
      In contrast, grazing pressure predicts pasture deficits with a high degree of
      accuracy. Large herbivores play a primary role in determining the severity of
      pasture deficits and variation across habitats. Grazing pressure also explains
      oscillations in plant biomass unrelated to rainfall. Plant biomass has declined
      steadily and biomass per unit of rainfall has fallen by a third, corresponding to
      a doubling in grazing intensity over the study period. The rising probability of
      forage deficits fits local pastoral perceptions of an increasing frequency of
      extreme shortfalls. The decline in forage is linked to sedentarization, range
      loss and herbivore compression into drought refuges, rather than climate change.
      The results show that the decline in rangeland productivity and increasing
      frequency of pasture shortfalls can be ameliorated by better husbandry practices
      and reinforces the need for ground monitoring to complement remote sensing in
      forecasting pasture shortfalls. 

PMID- 26317511
TI  - PGC-1alpha Promoter Methylation in Parkinson's Disease.
AB  - The etiopathogenesis of sporadic Parkinson's disease (PD) remains elusive
      although mitochondrial dysfunction has long been implicated. Recent evidence
      revealed reduced expression of peroxisome proliferator-activated receptor gamma
      coactivator-1 alpha (PGC-1alpha) and downstream regulated nuclear encoded
      respiratory complex genes in affected brain tissue from PD patients. We sought to
      determine whether epigenetic modification of the PGC-1alpha gene could account
      for diminished expression. In substantia nigra from PD patients but not control
      subjects, we show significant promoter-proximal non-canonical cytosine
      methylation of the PGC-1alpha gene but not an adjacent gene. As neuroinflammation
      is a prominent feature of PD and a mediator of epigenetic change, we evaluated
      whether the pro-inflammatory fatty acid, palmitate, would stimulate PGC-1alpha
      promoter methylation in different cell types from the CNS. Indeed, in mouse
      primary cortical neurons, microglia and astrocytes, palmitate causes PGC-1alpha
      gene promoter non-canonical cytosine methylation, reduced expression of the gene
      and reduced mitochondrial content. Moreover, intracerebroventricular (ICV)
      injection of palmitate to transgenic human alpha-synuclein mutant mice resulted
      in increased PGC-1alpha promoter methylation, decreased PGC-1alpha expression and
      reduced mitochondrial content in substantia nigra. Finally we provide evidence
      that dysregulation of ER stress and inflammatory signaling is associated with PGC
      1alpha promoter methylation. Together, these data strengthen the connection
      between saturated fatty acids, neuroflammation, ER stress, epigenetic alteration
      and bioenergetic compromise in PD. 

PMID- 26317513
TI  - SncRNA715 Inhibits Schwann Cell Myelin Basic Protein Synthesis.
AB  - Myelin basic proteins (MBP) are major constituents of the myelin sheath in the
      central nervous system (CNS) and the peripheral nervous system (PNS). In the CNS
      Mbp translation occurs locally at the axon-glial contact site in a neuronal
      activity-dependent manner. Recently we identified the small non-coding RNA 715
      (sncRNA715) as a key inhibitor of Mbp translation during transport in
      oligodendrocytes. Mbp mRNA localization in Schwann cells has been observed, but
      has not been investigated in much detail. Here we could confirm translational
      repression of Mbp mRNA in Schwann cells. We show that sncRNA715 is expressed and
      its levels correlate inversely with MBP in cultured Schwann cells and in the
      sciatic nerve in vivo. Furthermore we could reduce MBP protein levels in cultured
      Schwann cells by increasing the levels of the inhibitory sncRNA715. Our findings
      suggest similarities in sncRNA715-mediated translational repression of Mbp mRNA
      in oligodendrocytes and Schwann cells. 

PMID- 26317514
TI  - Social Bonds and Exercise: Evidence for a Reciprocal Relationship.
AB  - In two experimental studies, we investigated mechanisms hypothesized to underpin
      two pervasive and interrelated phenomena: that certain forms of group movement
      and exercise lead to social bonding and that social bonding can lead to enhanced
      exercise performance. In Study 1, we manipulated synchrony and exercise intensity
      among rowers and found that, compared with low intensity exercise, moderate
      intensity exercise led to significantly higher levels of cooperation in an
      economic game; no effect of synchrony vs. non-synchrony was found. In Study 2, we
      investigated the effects of bonding on performance, using synchrony as a cue of
      existing supportive social bonds among participants. An elite, highly bonded team
      of rugby players participated in solo, synchronized, and non-synchronized warm-up
      sessions; participants' anaerobic performance significantly improved after the
      brief synchronous warm-up relative to the non-synchronous warm-up. The findings
      substantiate claims concerning the reciprocal links between group exercise and
      social bonding, and may help to explain the ubiquity of collective physical
      activity across cultural domains as varied as play, ritual, sport, and dance. 

PMID- 26317515
TI  - Ribavirin Inhibits the Activity of mTOR/eIF4E, ERK/Mnk1/eIF4E Signaling Pathway
      and Synergizes with Tyrosine Kinase Inhibitor Imatinib to Impair Bcr-Abl Mediated
      Proliferation and Apoptosis in Ph+ Leukemia.
AB  - The eukaryotic translation initiation factor 4E (eIF4E), which is the main
      composition factor of eIF4F translation initiation complex, influences the growth
      of tumor through modulating cap-dependent protein translation. Previous studies
      reported that ribavirin could suppress eIF4E-controlled translation and reduce
      the synthesis of onco-proteins. Here, we investigated the anti-leukemic effects
      of ribavirin alone or in combination with tyrosine kinase inhibitor imatinib in
      Philadelphia chromosome positive (Ph+) leukemia cell lines SUP-B15 (Ph+ acute
      lymphoblastic leukemia cell line, Ph+ ALL) and K562 (chronic myelogenous leukemia
      cell line, CML). Our results showed that ribavirin had anti-proliferation effect;
      it down-regulated the phosphorylation levels of Akt, mTOR, 4EBP1, and eIF4E
      proteins in the mTOR/eIF4E signaling pathway, and MEK, ERK, Mnk1 and eIF4E
      proteins in ERK/Mnk1/eIF4E signaling pathway; reduced the expression of Mcl-1 (a
      translation substrates of eIF4F translation initiation complex) at protein
      synthesis level not mRNA transcriptional level; and induced cell apoptosis in
      both SUP-B15 and K562. 7-Methyl-guanosine cap affinity assay further demonstrated
      that ribavirin remarkably increased the eIF4E binding to 4EBP1 and decreased the
      combination of eIF4E with eIF4G, consequently resulting in a major inhibition of
      eIF4F complex assembly. The combination of ribavirin with imatinib enhanced
      antileukemic effects mentioned above, indicating that two drugs have synergistic
      anti-leukemic effect. Consistent with the cell lines, similar results were
      observed in Ph+ acute lymphoblastic primary leukemic blasts; however, the anti
      proliferative role of ribavirin in other types of acute primary leukemic blasts
      was not obvious, which indicated that the anti-leukemic effect of ribavirin was
      different in cell lineages. 

PMID- 26317516
TI  - Lowering Cardiovascular Disease Risk for People with Severe Mental Illnesses in
      Primary Care: A Focus Group Study.
AB  - BACKGROUND: People with severe mental illnesses die early from cardiovascular
      disease. Evidence is lacking regarding effective primary care based interventions
      to tackle this problem. AIM: To identify current procedures for, barriers to, and
      facilitators of the delivery of primary care based interventions for lowering
      cardiovascular risk for people with severe mental illnesses. METHOD: 75 GPs,
      practice nurses, service users, community mental health staff and carers in UK GP
      practice or community mental health settings were interviewed in 14 focus groups
      which were audio-recorded, transcribed and analysed using Framework Analysis.
      RESULTS: Five barriers to delivering primary care based interventions for
      lowering cardiovascular risk in people with severe mental illnesses were
      identified by the groups: negative perceptions of people with severe mental
      illnesses amongst some health professionals, difficulties accessing GP and
      community-based services, difficulties in managing a healthy lifestyle, not
      attending appointments, and a lack of awareness of increased cardiovascular risk
      in people with severe mental illnesses by some health professionals. Identified
      facilitators included involving supportive others, improving patient engagement
      with services, continuity of care, providing positive feedback in consultations
      and goal setting. CONCLUSION: We identified a range of factors which can be
      incorporated in to the design, delivery and evaluation of services to reduce
      cardiovascular risk for people with severe mental illnesses in primary care. The
      next step is determining the clinical and cost effectiveness of primary care
      based interventions for lowering cardiovascular risk in people with severe mental
      illnesses, and evaluating the most important components of such interventions.

PMID- 26317517
TI  - Improved Quantification, Propagation, Purification and Storage of the Obligate
      Intracellular Human Pathogen Orientia tsutsugamushi.
AB  - BACKGROUND: Scrub typhus is a leading cause of serious febrile illness in rural
      Southeast Asia. The causative agent, Orientia tsutsugamushi, is an obligate
      intracellular bacterium that is transmitted to humans by the bite of a
      Leptotrombidium mite. Research into the basic mechanisms of cell biology and
      pathogenicity of O. tsutsugamushi has lagged behind that of other important human
      pathogens. One reason for this is that O. tsutsugamushi is an obligate
      intracellular bacterium that can only be cultured in mammalian cells and that
      requires specific methodologies for propagation and analysis. Here, we have
      performed a body of work designed to improve methods for quantification,
      propagation, purification and long-term storage of this important but neglected
      human pathogen. These results will be useful to other researchers working on O.
      tsutsugamushi and also other obligate intracellular pathogens such as those in
      the Rickettsiales and Chlamydiales families. METHODOLOGY: A clinical isolate of
      O. tsutsugamushi was grown in cultured mouse embryonic fibroblast (L929) cells.
      Bacterial growth was measured using an O. tsutsugamushi-specific qPCR assay.
      Conditions leading to improvements in viability and growth were monitored in
      terms of the effect on bacterial cell number after growth in cultured mammalian
      cells. KEY RESULTS: Development of a standardised growth assay to quantify
      bacterial replication and viability in vitro. Quantitative comparison of
      different DNA extraction methods. Quantification of the effect on growth of FBS
      concentration, daunorubicin supplementation, media composition, host cell
      confluence at infection and frequency of media replacement. Optimisation of
      bacterial purification including a comparison of host cell lysis methods,
      purification temperature, bacterial yield calculations and bacterial pelleting at
      different centrifugation speeds. Quantification of bacterial viability loss after
      long term storage and freezing under a range of conditions including different
      freezing buffers and different rates of freezing. CONCLUSIONS: Here we present a
      standardised method for comparing the viability of O. tsutsugamushi after
      purification, treatment and propagation under various conditions. Taken together,
      we present a body of data to support improved techniques for propagation,
      purification and storage of this organism. This data will be useful both for
      improving clinical isolation rates as well as performing in vitro cell biology
      experiments.

PMID- 26317518
TI  - Proprioceptive Interaction between the Two Arms in a Single-Arm Pointing Task.
AB  - Proprioceptive signals coming from both arms are used to determine the perceived
      position of one arm in a two-arm matching task. Here, we examined whether the
      perceived position of one arm is affected by proprioceptive signals from the
      other arm in a one-arm pointing task in which participants specified the
      perceived position of an unseen reference arm with an indicator paddle. Both arms
      were hidden from the participant's view throughout the study. In Experiment 1,
      with both arms placed in front of the body, the participants received 70-80 Hz
      vibration to the elbow flexors of the reference arm (= right arm) to induce the
      illusion of elbow extension. This extension illusion was compared with that when
      the left arm elbow flexors were vibrated or not. The degree of the vibration
      induced extension illusion of the right arm was reduced in the presence of left
      arm vibration. In Experiment 2, we found that this kinesthetic interaction
      between the two arms did not occur when the left arm was vibrated in an abducted
      position. In Experiment 3, the vibration-induced extension illusion of one arm
      was fully developed when this arm was placed at an abducted position, indicating
      that the brain receives increased proprioceptive input from a vibrated arm even
      if the arm was abducted. Our results suggest that proprioceptive interaction
      between the two arms occurs in a one-arm pointing task when the two arms are
      aligned with one another. The position sense of one arm measured using a pointer
      appears to include the influences of incoming information from the other arm when
      both arms were placed in front of the body and parallel to one another.

PMID- 26317519
TI  - Associations between Maternal Biomarkers of Phthalate Exposure and Inflammation
      Using Repeated Measurements across Pregnancy.
AB  - Phthalate exposure is prevalent in populations worldwide, including pregnant
      women. Maternal urinary metabolite concentrations have been associated with
      adverse reproductive outcomes, but underlying mechanisms remain unclear. Here we
      investigate inflammation as a possible pathway by examining phthalates in
      association with inflammation biomarkers, including C-reactive protein (CRP) and
      a panel of cytokines (IL-1beta, IL-6, IL-10, and TNF-alpha) in a repeated
      measures analysis of pregnant women (N = 480). Urinary phthalate metabolites and
      plasma inflammation biomarkers were measured from samples collected at up to four
      visits per subject during gestation (median 10, 18, 26, and 35 weeks).
      Associations were examined using mixed models to account for within-individual
      correlation of measures. Few statistically significant associations or clear
      trends were observed, although in full models mono-carboxypropyl phthalate (MCPP)
      was significantly (percent change with interquartile range increase in exposure
      [%Delta] = 8.89, 95% confidence interval [CI] = 3.28, 14.8), and mono-benzyl
      phthalate (MBzP) was suggestively (%Delta = 6.79, 95%CI = -1.21, 15.4) associated
      with IL-6. Overall these findings show little evidence of an association between
      phthalate exposure and peripheral inflammation in pregnant women. To investigate
      inflammation as a mechanism of phthalate effects in humans, biomarkers from
      target tissues or fluids, though difficult to measure in large-scale studies, may
      be necessary to detect effects. 

PMID- 26317520
TI  - Association of MTOR and AKT Gene Polymorphisms with Susceptibility and Survival
      of Gastric Cancer.
AB  - BACKGROUND: The phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB,
      AKT)/mammalian target of rapamycin (mTOR) signaling pathway plays a critical role
      in angiogenesis and cell growth, proliferation, metabolism, migration,
      differentiation, and apoptosis. Genetic diversity in key factors of this pathway
      may influence protein function and signal transduction, contributing to disease
      initiation and progression. Studies suggest that MTOR rs1064261 and AKT rs1130233
      polymorphisms are associated with risk and/or prognosis of multiple cancer types.
      However, this relationship with gastric cancer (GC) remains unclear. The aim of
      this study was to investigate the role of MTOR and AKT polymorphisms in the risk
      and prognosis of GC. METHODS: The Sequenom MassARRAY platform was used to
      genotype 1842 individuals for MTOR rs1064261 T->C and AKT rs1130233 G->A
      polymorphisms. ELISA was used to detect Helicobacter pylori antibodies in serum.
      Immunohistochemical analysis was used to detect total and phosphorylated MTOR and
      AKT proteins. RESULTS: The MTOR rs1064261 (TC+CC) genotype and the AKT rs1130233
      (GA+AA) genotype were associated with increased risk of GC in men (P = 0.049, P =
      0.030). In H. pylori-negative individuals, the AKT rs1130233 GA and (GA+AA)
      genotypes were related to increased risk of atrophic gastritis (AG; P = 0.012, P
      = 0.024). Notably, the AKT rs1130233 (GA+AA) genotype demonstrated significant
      interactions with H. pylori in disease progression from healthy controls (CON) to
      AG (P = 0.013) and from AG to GC (P = 0.049). Additionally, for individuals with
      the AKT rs1130233 variant, those in the H. pylori-positive group had higher
      levels of phosphorylated AKT (p-AKT) expression. The AKT rs1130233 genotype was
      found to be associated with clinicopathological parameters including lymph node
      metastasis and alcohol drinking (P<0.05). CONCLUSION: MTOR rs1064261and AKT
      rs1130233 polymorphisms were associated with increased GC risk in males and
      increased AG risk in H. pylori-negative individuals. A significant interaction
      existed between the AKT rs1130233 genotype and H. pylori infection in CON->AG->GC
      disease progression. The AKT rs1130233 genotype influenced p-AKT protein
      expression in H. pylori-infected individuals.

PMID- 26317521
TI  - Consequences of Location-Dependent Organ of Corti Micro-Mechanics.
AB  - The cochlea performs frequency analysis and amplification of sounds. The graded
      stiffness of the basilar membrane along the cochlear length underlies the
      frequency-location relationship of the mammalian cochlea. The somatic motility of
      outer hair cell is central for cochlear amplification. Despite two to three
      orders of magnitude change in the basilar membrane stiffness, the force capacity
      of the outer hair cell's somatic motility, is nearly invariant over the cochlear
      length. It is puzzling how actuators with a constant force capacity can operate
      under such a wide stiffness range. We hypothesize that the organ of Corti sets
      the mechanical conditions so that the outer hair cell's somatic motility
      effectively interacts with the media of traveling waves-the basilar membrane and
      the tectorial membrane. To test this hypothesis, a computational model of the
      gerbil cochlea was developed that incorporates organ of Corti structural
      mechanics, cochlear fluid dynamics, and hair cell electro-physiology. The model
      simulations showed that the micro-mechanical responses of the organ of Corti are
      different along the cochlear length. For example, the top surface of the organ of
      Corti vibrated more than the bottom surface at the basal (high frequency)
      location, but the amplitude ratio was reversed at the apical (low frequency)
      location. Unlike the basilar membrane stiffness varying by a factor of 1700 along
      the cochlear length, the stiffness of the organ of Corti complex felt by the
      outer hair cell remained between 1.5 and 0.4 times the outer hair cell stiffness.
      The Y-shaped structure in the organ of Corti formed by outer hair cell, Deiters
      cell and its phalange was the primary determinant of the elastic reactance
      imposed on the outer hair cells. The stiffness and geometry of the Deiters cell
      and its phalange affected cochlear amplification differently depending on the
      location. 

PMID- 26317523
TI  - Influence of Tree Species Composition and Community Structure on Carbon Density
      in a Subtropical Forest.
AB  - We assessed the impact of species composition and stand structure on the spatial
      variation of forest carbon density using data collected from a 4-ha plot in a
      subtropical forest in southern China. We found that 1) forest biomass carbon
      density significantly differed among communities, reflecting a significant effect
      of community structure and species composition on carbon accumulation; 2) soil
      organic carbon density increased whereas stand biomass carbon density decreased
      across communities, indicating that different mechanisms might account for the
      accumulation of stand biomass carbon and soil organic carbon in the subtropical
      forest; and 3) a small number of tree individuals of the medium- and large
      diameter class contributed predominantly to biomass carbon accumulation in the
      community, whereas a large number of seedlings and saplings were responsible for
      a small proportion of the total forest carbon stock. These findings demonstrate
      that both biomass carbon and soil carbon density in the subtropical forest are
      sensitive to species composition and community structure, and that heterogeneity
      in species composition and stand structure should be taken into account to ensure
      accurate forest carbon accounting. 

PMID- 26317522
TI  - Binding Interactions of Keratin-Based Hair Fiber Extract to Gold, Keratin, and
      BMP-2.
AB  - Hair-derived keratin biomaterials composed mostly of reduced keratin proteins
      (kerateines) have demonstrated their utility as carriers of biologics and drugs
      for tissue engineering. Electrostatic forces between negatively-charged keratins
      and biologic macromolecules allow for effective drug retention; attraction to
      positively-charged growth factors like bone morphogenetic protein 2 (BMP-2) has
      been used as a strategy for osteoinduction. In this study, the intermolecular
      surface and bulk interaction properties of kerateines were investigated. Thiol
      rich kerateines were chemisorbed onto gold substrates to form an irreversible 2
      nm rigid layer for surface plasmon resonance analysis. Kerateine-to-kerateine
      cohesion was observed in pH-neutral water with an equilibrium dissociation
      constant (KD) of 1.8 * 10(-4) M, indicating that non-coulombic attractive forces
      (i.e. hydrophobic and van der Waals) were at work. The association of BMP-2 to
      kerateine was found to be greater (KD = 1.1 * 10(-7) M), within the range of
      specific binding. Addition of salts (phosphate-buffered saline; PBS) shortened
      the Debye length or the electrostatic field influence which weakened the
      kerateine-BMP-2 binding (KD = 3.2 * 10(-5) M). BMP-2 in bulk kerateine gels
      provided a limited release in PBS (~ 10% dissociation in 4 weeks), suggesting
      that electrostatic intermolecular attraction was significant to retain BMP-2
      within the keratin matrix. Complete dissociation between kerateine and BMP-2
      occurred when the PBS pH was lowered (to 4.5), below the keratin isoelectric
      point of 5.3. This phenomenon can be attributed to the protonation of keratin at
      a lower pH, leading to positive-positive repulsion. Therefore, the dynamics of
      kerateine-BMP-2 binding is highly dependent on pH and salt concentration, as well
      as on BMP-2 solubility at different pH and molarity. The study findings may
      contribute to our understanding of the release kinetics of drugs from keratin
      biomaterials and allow for the development of better, more clinically relevant
      BMP-2-conjugated systems for bone repair and regeneration.

PMID- 26317524
TI  - Assessment of donor heart viability during ex vivo heart perfusion.
AB  - Ex vivo heart perfusion (EVHP) may facilitate resuscitation of discarded donor
      hearts and expand the donor pool; however, a reliable means of demonstrating
      organ viability prior to transplantation is required. Therefore, we sought to
      identify metabolic and functional parameters that predict myocardial performance
      during EVHP. To evaluate the parameters over a broad spectrum of organ function,
      we obtained hearts from 9 normal pigs and 37 donation after circulatory death
      pigs and perfused them ex vivo. Functional parameters obtained from a left
      ventricular conductance catheter, oxygen consumption, coronary vascular
      resistance, and lactate concentration were measured, and linear regression
      analyses were performed to identify which parameters best correlated with
      myocardial performance (cardiac index: mL.min(-1).g(-1)). Functional parameters
      exhibited excellent correlation with myocardial performance and demonstrated high
      sensitivity and specificity for identifying hearts at risk of poor post
      transplant function (ejection fraction: R(2) = 0.80, sensitivity = 1.00,
      specificity = 0.85; stroke work: R(2) = 0.76, sensitivity = 1.00, specificity =
      0.77; minimum dP/dt: R(2) = 0.74, sensitivity = 1.00, specificity = 0.54; tau:
      R(2) = 0.51, sensitivity = 1.00, specificity = 0.92), whereas metabolic
      parameters were limited in their ability to predict myocardial performance
      (oxygen consumption: R(2) = 0.28; coronary vascular resistance: R(2) = 0.20;
      lactate concentration: R(2) = 0.02). We concluded that evaluation of functional
      parameters provides the best assessment of myocardial performance during EVHP,
      which highlights the need for an EVHP device capable of assessing the donor heart
      in a physiologic working mode. 

PMID- 26317525
TI  - Risk Factors of Bone Mass Loss at the Lumbar Spine: A Longitudinal Study in
      Healthy Korean Pre- and Perimenopausal Women Older than 40 Years.
AB  - Longitudinal studies on bone mass decline for healthy women are sparse. We
      performed a retrospective longitudinal study to evaluate the factor associated
      with bone mass changes at the lumbar spine in healthy Korean pre- and
      perimenopausal women over the age of 40. We examined the relation of blood tests
      including thyroid function tests at baseline and follow-up to the annual
      percentage changes in average BMD of L2-L4 (A%DeltaLSBMD). Four hundred and forty
      three subjects without diseases or medications pertaining to bone metabolism were
      analyzed. The mean A%DeltaLSBMD in these subjects was -0.45%/year. Though a
      significant correlation was observed between the A%DeltaLSBMD and age, serum
      thyroid-stimulating hormone (TSH) level, total cholesterol (TC) level, low
      density lipoprotein cholesterol (LDL-C) level, and estimated glomerular
      filtration rate (eGFR) at baseline and follow-up, there was a weak correlation
      between A%DeltaLSBMD and these variables. From multiple linear regression
      analyses, the percent body fat, age, serum TSH level, serum uric acid level, and
      the menopause at follow-up were showed to have a significant association with the
      A%DeltaLSBMD. Unlike age, percent body fat, and menopause at follow-up, which had
      a negative association with the A%DeltaLSBMD, serum TSH level and serum uric acid
      level, had a positive association with the A%DeltaLSBMD. The results from our
      study showed that the notable risk factors of BMD loss at the lumbar spine in
      population of our study were advancing age, menopause, higher percent body fat,
      lower normal TSH, and lower serum uric acid levels. 

PMID- 26317526
TI  - An exploration of the ecological validity of the Virtual Action Planning
      Supermarket (VAP-S) with people with schizophrenia.
AB  - People with schizophrenia often have functional limitations that affect their
      daily activities due to executive function deficits. One way to assess these
      deficits is through the use of virtual reality programmes that reproduce real
      life instrumental activities of daily living (IADLs). One such programme is the
      Virtual Action Planning-Supermarket (VAP-S). This exploratory study aimed to
      examine the ecological validity of this programme, specifically, how task
      performance in both virtual and natural environments compares. Case studies were
      used and involved five participants with schizophrenia, who were familiar with
      grocery shopping. They were assessed during both the VAP-S shopping task and a
      real-life grocery shopping task using an observational assessment tool, the
      Perceive, Recall, Plan and Perform (PRPP) System of Task Analysis. The results
      show that when difficulties were present in the virtual task, difficulties were
      also observed in the real-life task. For some participants, greater difficulties
      were observed in the virtual task. These difficulties could be explained by the
      presence of perceptual deficits and problems remembering the required sequenced
      actions in the virtual task. In conclusion, performance on the VAP-S by these
      five participants was generally comparable to the performance in a natural
      environment.

PMID- 26317527
TI  - Effects of Estrogens on Adipokines and Glucose Homeostasis in Female Aromatase
      Knockout Mice.
AB  - The maintenance of glucose homeostasis within the body is crucial for constant
      and precise performance of energy balance and is sustained by a number of
      peripheral organs. Estrogens are known to play a role in the maintenance of
      glucose homeostasis. Aromatase knockout (ArKO) mice are estrogen-deficient and
      display symptoms of dysregulated glucose metabolism. We aim to investigate the
      effects of estrogen ablation and exogenous estrogen administration on glucose
      homeostasis regulation. Six month-old female wildtype, ArKO, and 17beta-estradiol
      (E2) treated ArKO mice were subjected to whole body tolerance tests, serum
      examination of estrogen, glucose and insulin, ex-vivo muscle glucose uptake, and
      insulin signaling pathway analyses. Female ArKO mice display increased body
      weight, gonadal (omental) adiposity, hyperinsulinemia, and liver triglycerides,
      which were ameliorated upon estrogen treatment. Tolerance tests revealed that
      estrogen-deficient ArKO mice were pyruvate intolerant hence reflecting
      dysregulated hepatic gluconeogenesis. Analyses of skeletal muscle, liver, and
      adipose tissues supported a hepatic-based glucose dysregulation, with a down
      regulation of Akt phosphorylation (a key insulin signaling pathway molecule) in
      the ArKO liver, which was improved with E2 treatment. Concurrently, estrogen
      treatment lowered ArKO serum leptin and adiponectin levels and increased
      inflammatory adipokines such as tumour necrosis factor alpha (TNFalpha) and
      interleukin 6 (IL6). Furthermore, estrogen deficiency resulted in the
      infiltration of CD45 macrophages into gonadal adipose tissues, which cannot be
      reversed by E2 treatment. This study describes the effects of estrogens on
      glucose homeostasis in female ArKO mice and highlights a primary phenotype of
      hepatic glucose dysregulation and a parallel estrogen modified adipokine profile.

PMID- 26317528
TI  - An Economic Evaluation of TENS in Addition to Usual Primary Care Management for
      the Treatment of Tennis Elbow: Results from the TATE Randomized Controlled Trial.
AB  - BACKGROUND: The TATE trial was a multicentre pragmatic randomized controlled
      trial of supplementing primary care management (PCM)-consisting of a GP
      consultation followed by information and advice on exercises-with transcutaneous
      electrical nerve stimulation (TENS), to reduce pain intensity in patients with
      tennis elbow. This paper reports the health economic evaluation. METHODS AND
      FINDINGS: Adults with new diagnosis of tennis elbow were recruited from 38
      general practices in the UK, and randomly allocated to PCM (n = 120) or PCM plus
      TENS (n = 121). Outcomes included reduction in pain intensity and quality
      adjusted-life-years (QALYs) based on the EQ5D and SF6D. Two economic perspectives
      were evaluated: (i) healthcare-inclusive of NHS and private health costs for the
      tennis elbow; (ii) societal-healthcare costs plus productivity losses through
      work absenteeism. Mean outcome and cost differences between the groups were
      evaluated using a multiple imputed dataset as the base case evaluation, with
      uncertainty represented in cost-effectiveness planes and through probabilistic
      cost-effectiveness acceptability curves). Incremental healthcare cost was L33
      (95%CI -40, 106) and societal cost L65 (95%CI -307, 176) for PCM plus TENS. Mean
      differences in outcome were: 0.11 (95%CI -0.13, 0.35) for change in pain (0-10
      pain scale); -0.015 (95%CI -0.058, 0.029) for QALYEQ5D; 0.007 (95%CI -0.022,
      0.035) for QALYSF6D (higher score differences denote greater benefit for PCM plus
      TENS). The ICER (incremental cost effectiveness ratio) for the main evaluation of
      mean difference in societal cost (L) relative to mean difference in pain outcome
      was -582 (95%CI -8666, 8113). However, incremental ICERs show differences in cost
      effectiveness of additional TENS, according to the outcome being evaluated.
      CONCLUSION: Our findings do not provide evidence for or against the cost
      effectiveness of TENS as an adjunct to primary care management of tennis elbow.

PMID- 26317530
TI  - Quantifying and Mapping the Supply of and Demand for Carbon Storage and
      Sequestration Service from Urban Trees.
AB  - Studies that assess the distribution of benefits provided by ecosystem services
      across urban areas are increasingly common. Nevertheless, current knowledge of
      both the supply and demand sides of ecosystem services remains limited, leaving a
      gap in our understanding of balance between ecosystem service supply and demand
      that restricts our ability to assess and manage these services. The present study
      seeks to fill this gap by developing and applying an integrated approach to
      quantifying the supply and demand of a key ecosystem service, carbon storage and
      sequestration, at the local level. This approach follows three basic steps: (1)
      quantifying and mapping service supply based upon Light Detection and Ranging
      (LiDAR) processing and allometric models, (2) quantifying and mapping demand for
      carbon sequestration using an indicator based on local anthropogenic CO2
      emissions, and (3) mapping a supply-to-demand ratio. We illustrate this approach
      using a portion of the Twin Cities Metropolitan Area of Minnesota, USA. Our
      results indicate that 1735.69 million kg carbon are stored by urban trees in our
      study area. Annually, 33.43 million kg carbon are sequestered by trees, whereas
      3087.60 million kg carbon are emitted by human sources. Thus, carbon
      sequestration service provided by urban trees in the study location play a minor
      role in combating climate change, offsetting approximately 1% of local
      anthropogenic carbon emissions per year, although avoided emissions via storage
      in trees are substantial. Our supply-to-demand ratio map provides insight into
      the balance between carbon sequestration supply in urban trees and demand for
      such sequestration at the local level, pinpointing critical locations where
      higher levels of supply and demand exist. Such a ratio map could help planners
      and policy makers to assess and manage the supply of and demand for carbon
      sequestration. 

PMID- 26317531
TI  - 2015 4(th) TERMIS World Congress Boston, Massachusetts September 8-11, 2015.

PMID- 26317529
TI  - Modeling and Classification of Kinetic Patterns of Dynamic Metabolic Biomarkers
      in Physical Activity.
AB  - The objectives of this work were the classification of dynamic metabolic
      biomarker candidates and the modeling and characterization of kinetic regulatory
      mechanisms in human metabolism with response to external perturbations by
      physical activity. Longitudinal metabolic concentration data of 47 individuals
      from 4 different groups were examined, obtained from a cycle ergometry cohort
      study. In total, 110 metabolites (within the classes of acylcarnitines, amino
      acids, and sugars) were measured through a targeted metabolomics approach,
      combining tandem mass spectrometry (MS/MS) with the concept of stable isotope
      dilution (SID) for metabolite quantitation. Biomarker candidates were selected by
      combined analysis of maximum fold changes (MFCs) in concentrations and P-values
      resulting from statistical hypothesis testing. Characteristic kinetic signatures
      were identified through a mathematical modeling approach utilizing polynomial
      fitting. Modeled kinetic signatures were analyzed for groups with similar
      behavior by applying hierarchical cluster analysis. Kinetic shape templates were
      characterized, defining different forms of basic kinetic response patterns, such
      as sustained, early, late, and other forms, that can be used for metabolite
      classification. Acetylcarnitine (C2), showing a late response pattern and having
      the highest values in MFC and statistical significance, was classified as late
      marker and ranked as strong predictor (MFC = 1.97, P < 0.001). In the class of
      amino acids, highest values were shown for alanine (MFC = 1.42, P < 0.001),
      classified as late marker and strong predictor. Glucose yields a delayed response
      pattern, similar to a hockey stick function, being classified as delayed marker
      and ranked as moderate predictor (MFC = 1.32, P < 0.001). These findings coincide
      with existing knowledge on central metabolic pathways affected in exercise
      physiology, such as beta-oxidation of fatty acids, glycolysis, and
      glycogenolysis. The presented modeling approach demonstrates high potential for
      dynamic biomarker identification and the investigation of kinetic mechanisms in
      disease or pharmacodynamics studies using MS data from longitudinal cohort
      studies. 

PMID- 26317534
TI  - Sociocultural Factors Affecting Unplanned Deliveries at Home: A Community-Based
      Case Control Study.
AB  - Unplanned home deliveries can vary with social and cultural factors. The aim of
      this study was to define the risk factors of unplanned home births. This case
      control study was conducted in Istanbul, Turkey. The study group was composed of
      229 women who had unplanned home delivery. Six factors (presence of health
      insurance, duration of living in Istanbul, educational status of the woman, the
      number of individuals living in the household, the age of the woman at the time
      of current delivery, and the status of having received care prior to delivery)
      were determined as independent risk factors for unplanned deliveries at home. 

PMID- 26317533
TI  - The Global Epidemiology of Impetigo: A Systematic Review of the Population
      Prevalence of Impetigo and Pyoderma.
AB  - OBJECTIVE: We conducted a comprehensive, systematic review of the global
      childhood population prevalence of impetigo and the broader condition pyoderma.
      METHODS: PubMed was systematically searched for impetigo or pyoderma studies
      published between January 1 1970 and September 30 2014. Two independent reviewers
      extracted data from each relevant article on the prevalence of impetigo.
      FINDINGS: Sixty-six articles relating to 89 studies met our inclusion criteria.
      Based on population surveillance, 82 studies included data on 145,028 children
      assessed for pyoderma or impetigo. Median childhood prevalence was 12.3% (IQR 4.2
      19.4%). Fifty-eight (65%) studies were from low or low-middle income countries,
      where median childhood prevalences were 8.4% (IQR 4.2-16.1%) and 14.5% (IQR 8.3
      20.9%), respectively. However, the highest burden was seen in underprivileged
      children from marginalised communities of high-income countries; median
      prevalence 19.4%, (IQR 3.9-43.3%). CONCLUSION: Based on data from studies
      published since 2000 from low and low-middle income countries, we estimate the
      global population of children suffering from impetigo at any one time to be in
      excess of 162 million, predominantly in tropical, resource-poor contexts.
      Impetigo is an under-recognised disease and in conjunction with scabies,
      comprises a major childhood dermatological condition with potential lifelong
      consequences if untreated.

PMID- 26317535
TI  - A Multi-Site Knowledge Attitude and Practice Survey of Ebola Virus Disease in
      Nigeria.
AB  - BACKGROUND: The 2014 Ebola Virus Disease (EVD) outbreak was characterised by
      fear, misconceptions and irrational behaviours. We conducted a knowledge attitude
      and practice survey of EVD in Nigeria to inform implementation of effective
      control measures. METHODS: Between July 30th and September 30th 2014, we
      undertook a cross sectional study on knowledge, attitude and practice (KAP) of
      Ebola Virus Disease (EVD) among adults of the general population and healthcare
      workers (HCW) in three states of Nigeria, namely Bayelsa, Cross River and Kano
      states. Demographic information and data on KAP were obtained using a self
      administered standardized questionnaire. The percentage KAP scores were
      categorised as good and poor. Independent predictors of good knowledge of EVD
      were ascertained using a binary logistic regression model. RESULTS: Out of 1035
      study participants with median age of 32 years, 648 (62.6%) were males, 846
      (81.7%) had tertiary education and 441 (42.6%) were HCW. There were 218, 239 and
      578 respondents from Bayelsa, Cross River and Kano states respectively. The
      overall median percentage KAP scores and interquartile ranges (IQR) were 79.46%
      (15.07%), 95.0% (33.33%) and 49.95% (37.50%) respectively. Out of the 1035
      respondents, 470 (45.4%), 544(52.56%) and 252 (24.35%) had good KAP of EVD
      defined using 80%, 90% and 70% score cut-offs respectively. Independent
      predictors of good knowledge of EVD were being a HCW (Odds Ratio-OR-2.89, 95%
      Confidence interval-CI of 1.41-5.90), reporting 'moderate to high fear of EVD'
      (OR-2.15, 95% CI-(1.47-3.13) and 'willingness to modify habit' (OR-1.68, 95% CI
      1.23-2.30). CONCLUSION: Our results reveal suboptimal EVD-related knowledge,
      attitude and practice among adults in Nigeria. To effectively control future
      outbreaks of EVD in Nigeria, there is a need to implement public sensitization
      programmes that improve understanding of EVD and address EVD-related myths and
      misconceptions, especially among the general population.

PMID- 26317536
TI  - Correction: Long-Term Urban Market Dynamics Reveal Increased Bushmeat Carcass
      Volume despite Economic Growth and Proactive Environmental Legislation on Bioko
      Island, Equatorial Guinea.

PMID- 26317538
TI  - A Four-Plex Real-Time PCR Assay, Based on rfbE, stx1, stx2, and eae Genes, for
      the Detection and Quantification of Shiga Toxin-Producing Escherichia coli O157
      in Cattle Feces.
AB  - Several real-time polymerase chain reaction (PCR) assays have been developed to
      detect and quantify Shiga toxin-producing Escherichia coli (STEC) O157:H7, but
      none have targeted the O-antigen specific gene (rfbEO157) in combination with the
      three major virulence genes, stx1, stx2, and eae. Our objectives were to develop
      and validate a four-plex, quantitative PCR (mqPCR) assay targeting rfbE(O157),
      stx1, stx2, and eae for the detection and quantification of STEC O157 in cattle
      feces, and compare the applicability of the assay to detect STEC O157 to a
      culture method and conventional PCR (cPCR) targeting the same four genes.
      Specificity of the mqPCR assay to differentially detect the four genes was
      confirmed with strains of O157 and non-O157 STEC with different profiles of
      target genes. In cattle feces spiked with pure cultures, detection limits were
      2.8*10(4) and 2.8*10(0) colony-forming units/g before and after enrichment,
      respectively. Detection of STEC O157 in feedlot cattle fecal samples (n=278) was
      compared between mqPCR, cPCR, and a culture method. The mqPCR detected 48.9%
      (136/278) of samples as positive for E. coli O157. Of the 100 samples that were
      randomly picked from 136 mqPCR-positive samples, 35 and 48 tested positive by
      cPCR and culture method, respectively. Of the 100 samples randomly chosen from
      142 mqPCR-negative samples, all were negative by cPCR, but 21 samples tested
      positive by the culture method. McNemar's chi-square tests indicated significant
      disagreement between the proportions of positive samples detected by the three
      methods. In conclusion, the mqPCR assay that targets four genes is a novel and
      more sensitive method than the cPCR or culture method to detect STEC O157 in
      cattle feces. However, the use of real-time PCR as a screening method to identify
      positive samples and then subjecting only positive samples to a culture method
      may underestimate the presence of STEC O157 in fecal samples.

PMID- 26317537
TI  - The potential impact of pneumococcal conjugate vaccine in Africa: Considerations
      and early lessons learned from the South African experience.
AB  - The introduction of pneumococcal conjugate vaccine (PCV) into the South African
      public immunization program since 2009 adopted a novel vaccination schedule of 3
      doses at 6, 14 and 40 weeks of age. Over the past 5 y it has been shown that
      infant PCV immunization in South Africa is effective in reducing the burden of
      invasive pneumococcal disease (IPD) among HIV-infected and HIV-uninfected
      children. Furthermore, indirect protection of unvaccinated age-groups (including
      high risk groups such as HIV-infected adults) against IPD was demonstrated
      despite the absence of any substantial catch-up campaign of older children. This
      indirect effect against IPD is corroborated by the temporal reduction in vaccine
      serotype colonization among age-groups targeted for PCV immunization as well as
      unvaccinated HIV-infected and HIV-uninfected adults, which was evident within 2 y
      of PCV introduction into the immunization program. Vaccine effectiveness has also
      been demonstrated in children against presumed bacterial pneumonia. The
      evaluation of the impact of PCV in South Africa, however, remains incomplete. The
      knowledge gaps remaining include the evaluation of PCV on the incidence of all
      cause pneumonia hospitalization among vaccinated and unvaccinated age-groups.
      Furthermore, ongoing surveillance is required to determine whether there is
      ongoing replacement disease by non-vaccine serotypes, which could offset the
      early gains associated with the immunization program in the country. 

PMID- 26317539
TI  - Quantitative Prevalence and Toxin Gene Profile of Bacillus cereus from Ready-to
      Eat Vegetables in South Korea.
AB  - Ready-to-eat (RTE) foods such as prepared vegetables are becoming an increasingly
      popular food choice. Since RTE vegetables are not commonly sterilized by heat
      treatment, contamination with foodborne pathogens such as Bacillus cereus (B.
      cereus) is a major concern. The objective of this study was to assess the
      quantitative prevalence and toxin gene profiles of B. cereus strains isolated
      from RTE vegetables. We found that 70 of the 145 (48%) tested retail vegetable
      salad and sprout samples were positive for B. cereus. The B. cereus isolates
      harbored at least one enterotoxin gene. The detection rates of nheABC, hblCDA,
      cytK, and entFM enterotoxin genes among all isolates were 97.1%, 100%, 81.4%, and
      98.6%, respectively. No strain carried the emetic toxin genes. Only 4 strains
      (5.7%) from the 70 isolates were psychrotrophic and were able to grow at 7
      degrees C. All of the psychrotrophic isolates possessed at least 1 enterotoxin
      gene. 

PMID- 26317540
TI  - Energy Sensing versus 2-Oxoglutarate Dependent ATPase Switch in the Control of
      Synechococcus PII Interaction with Its Targets NAGK and PipX.
AB  - PII proteins constitute a superfamily of highly conserved signaling devices,
      common in all domains of life. Through binding of the metabolites ATP, ADP and 2
      oxoglutarate (2-OG), they undergo conformational changes which allow them to
      regulate a variety of target proteins including enzymes, transport proteins and
      transcription factors. But, in reverse, these target proteins also modulate the
      metabolite sensing properties of PII, as has been recently shown. We used this
      effect to refine our PII based Forster resonance energy transfer (FRET) sensor
      and amplify its sensitivity towards ADP. With this enhanced sensor setup we
      addressed the question whether the PII protein from the model organism
      Synechococcus elongatus autonomously switches into the ADP conformation through
      ATPase activity as proposed in a recently published model. The present study
      disproves ATPase activity as a relevant mechanism for the transition of PII into
      the ADP state. In the absence of 2-OG, only the ATP/ADP ratio and concentration
      of ADP directs the competitive interaction of PII with two targets, one of which
      preferentially binds PII in the ATP-state, the other in the ADP-state. 

PMID- 26317542
TI  - ABT-263 induces apoptosis and synergizes with chemotherapy by targeting stemness
      pathways in esophageal cancer.
AB  - Activation of cancer stem cell signaling is central to acquired resistance to
      therapy in esophageal cancer (EC). ABT-263, a potent Bcl-2 family inhibitor, is
      active against many tumor types. However, effect of ABT-263 on EC cells and their
      resistant counterparts are unknown. Here we report that ABT-263 inhibited cell
      proliferation and induced apoptosis in human EC cells and their chemo-resistant
      counterparts. The combination of ABT-263 with 5-FU had synergistic lethal effects
      and amplified apoptosis that does not depend fully on its inhibition of BCL-2
      family proteins in EC cells. To further explore the novel mechanisms of ABT-263,
      proteomic array (RPPAs) were performed and gene set enriched analysis
      demonstrated that ABT-263 suppresses the expression of many oncogenes including
      genes that govern stemness pathways. Immunoblotting and immunofluorescence
      further confirmed reduction in protein expression and transcription in Wnt/beta
      catenin and YAP/SOX9 axes. Furthermore, ABT263 strongly suppresses cancer stem
      cell properties in EC cells and the combination of ABT-263 and 5-FU significantly
      reduced tumor growth in vivo and suppresses the expression of stemness genes.
      Thus, our findings demonstrated a novel mechanism of ABT-263 antitumor effect in
      EC and indicating that combination of ABT-263 with cytotoxic drugs is worthy of
      pursuit in patients with EC. 

PMID- 26317543
TI  - The sum of gains and losses of genes encoding the protein tyrosine kinase targets
      predicts response to multi-kinase inhibitor treatment: Characterization,
      validation, and prognostic value.
AB  - Validated predictive biomarkers for multi-tyrosine kinase inhibitors (MTKI)
      efficacy are lacking. We hypothesized that interindividual response variability
      is partially dependent on somatic DNA copy number alterations (SCNAs),
      particularly those of genes encoding the protein tyrosines targeted by MTKI
      (called target genes). Genomic alterations were investigated in MTKI responsive
      and non responsive patients with different histological subtypes included in the
      ProfiLER protocol (NCT 01774409). From March 2013 to August 2014, 58 patients
      with advanced cancer treated with one of 7 MTKIs were included in the ProfiLER
      trial and split into one discovery cohort (n = 13), and 2 validation cohorts (n =
      12 and 33). An analysis of the copy number alterations of kinase-coding genes for
      each of 7 MTKIs was conducted. A prediction algorithm (SUMSCAN) based on the
      presence of specific gene gains (Tumor Target Charge, TTC) and losses (Tumor
      Target Losses, TTL) was conceived and validated in 2 independent validation
      cohorts. MTKI sensitive tumors present a characteristic SCNA profile including a
      global gain profile, and specific gains for target genes while MTKI resistant
      tumors present the opposite. SUMSCAN favorable patients achieved longer
      progression-free and overall survival. This work shows that the copy number sum
      of kinase-coding genes enables the prediction of response of cancer patients to
      MTKI, opening a novel paradigm for the treatment selection of these patients. 

PMID- 26317541
TI  - A synthetic peptide targeting the BH4 domain of Bcl-2 induces apoptosis in
      multiple myeloma and follicular lymphoma cells alone or in combination with
      agents targeting the BH3-binding pocket of Bcl-2.
AB  - Bcl-2 inhibits apoptosis by two distinct mechanisms but only one is targeted to
      treat Bcl-2-positive malignancies. In this mechanism, the BH1-3 domains of Bcl-2
      form a hydrophobic pocket, binding and inhibiting pro-apoptotic proteins,
      including Bim. In the other mechanism, the BH4 domain mediates interaction of Bcl
      2 with inositol 1,4, 5-trisphosphate receptors (IP3Rs), inhibiting pro-apoptotic
      Ca2+ signals. The current anti-Bcl-2 agents, ABT-263 (Navitoclax) and ABT-199
      (Venetoclax), induce apoptosis by displacing pro-apoptotic proteins from the
      hydrophobic pocket, but do not inhibit Bcl-2-IP3R interaction. Therefore, to
      target this interaction we developed BIRD-2 (Bcl-2 IP3 Receptor Disruptor-2), a
      decoy peptide that binds to the BH4 domain, blocking Bcl-2-IP3R interaction and
      thus inducing Ca2+-mediated apoptosis in chronic lymphocytic leukemia, multiple
      myeloma, and follicular lymphoma cells, including cells resistant to ABT-263, ABT
      199, or the Bruton's tyrosine kinase inhibitor Ibrutinib. Moreover, combining
      BIRD-2 with ABT-263 or ABT-199 enhances apoptosis induction compared to single
      agent treatment. Overall, these findings provide strong rationale for developing
      novel therapeutic agents that mimic the action of BIRD-2 in targeting the BH4
      domain of Bcl-2 and disrupting Bcl-2-IP3R interaction. 

PMID- 26317544
TI  - KMT Set7/9 affects genotoxic stress response via the Mdm2 axis.
AB  - Genotoxic stress inflicted by anti-cancer drugs causes DNA breaks and genome
      instability. DNA double strand breaks induced by irradiation or pharmacological
      inhibition of Topoisomerase II activate ATM (ataxia-telangiectasia-mutated)
      kinase signalling pathway that in turn triggers cell cycle arrest and DNA repair.
      ATM-dependent gamma-phosphorylation of histone H2Ax and other histone
      modifications, including ubiquitnylation, promote exchange of histones and
      recruitment of DNA damage response (DDR) and repair proteins. Signal transduction
      pathways, besides DDR itself, also control expression of genes whose products
      cause cell cycle arrest and/or apoptosis thus ultimately affecting the
      sensitivity of cells to genotoxic stress. In this study, using a number of
      experimental approaches we provide evidence that lysine-specific
      methyltransferase (KMT) Set7/9 affects DDR and DNA repair, at least in part, by
      regulating the expression of an E3 ubiquitin ligase, Mdm2. Furthermore, we show
      that Set7/9 physically interacts with Mdm2. Several cancer cell lines with
      inverse expression of Set7/9 and Mdm2 displayed diminished survival in response
      to genotoxic stress. These findings are signified by our bioinformatics studies
      suggesting that the unleashed expression of Mdm2 in cancer patients with
      diminished expression of Set7/9 is associated with poor survival outcome. 

PMID- 26317545
TI  - Upregulation of COL6A1 is predictive of poor prognosis in clear cell renal cell
      carcinoma patients.
AB  - BACKGROUND: The extracellular matrix (ECM) is reported to play an important role
      in tumorigenesis and progression. Collagen VI is an important ECM protein. In
      this study, we investigated the potential role of the COL6A1 gene, which encodes
      the alpha1 polypeptide of collagen VI, in the biological functions involved in
      the progression and outcome of clear cell renal cell carcinoma (ccRCC). MATERIALS
      AND METHODS: A total of 288 ccRCC patients who underwent radical nephrectomy (RN)
      or nephron sparing nephrectomy (NSS) at Fudan University Shanghai Cancer Center
      (FUSCC) were enrolled. Total RNA was extracted from frozen samples obtained from
      the tissue bank of FUSCC and expression of COL6A1 was determined by qRT-PCR. The
      clinical relationship between COL6A1 expression and ccRCC prognosis was analyzed.
      These data were then validated in the Cancer Genome Atlas (TCGA) cohort. We also
      investigated the effect of COL6A1 overexpression in a xenografted tumor model in
      nude mice in vivo. RESULTS: In multivariate analysis of TCGA cohorts, COL6A1 high
      expression was predictive of poor prognosis in ccRCC patients' overall survival
      (OS) (HR: 2.588 95%CI 1.616-4.146) and disease free survival(DFS) (HR: 3.106
      95%CI 1.534-6.288). In FUSCC cohorts, after adjusted for relevant factors, the
      COL6A1 expression indicates poor prognosis in ccRCC patients's OS (HR 2.211; 95%
      CI, 1.360-8.060) and DFS (HR 3.052; 95%CI, 1.500-6.210). COL6A1 overexpression
      promoted tumor growth in xenografted nude mice. CONCLUSION: Increased COL6A1
      expression correlates with poor prognosis in ccRCC patients. Moreover, COL6A1
      stimulates tumor growth in vivo.

PMID- 26317546
TI  - SALL4 is a novel therapeutic target in intrahepatic cholangiocarcinoma.
AB  - Intrahepatic cholangiocarcinoma (ICC) is the most common and deadly disease of
      the biliary tree due to its poor prognosis. Sal-like protein 4 (SALL4), a stem
      cell marker, has been identified as a potential target for aggressive
      hepatocellular carcinoma (HCC). In our study, 175 ICC cases with an average age
      of 55 years were included, and 53% (93/175) were male. And 28 adjacent non-tumor
      tissues were also collected. The SALL4-positive immunoreactivity was detected in
      a total of 102 ICC cases (58%), whereas all 28 adjacent tissues showed negative
      staining. Univariate analysis, showed that the SALL4-positive ICC cases had
      significantly more frequent lymph nodal metastasis (P = 0.0460), vascular
      invasion (P < 0.0001), and nerve invasion (P < 0.0001). Furthermore, the strong
      SALL4-positive cases (n = 7, 5 months) had shorter overall survival, when
      compared to moderate SALL4-positive (n = 46, 9 months) or SALL4-negative cases (n
      = 73, 7 months), respectively. Our data also suggest that SALL4 may be involved
      in the regulation of epithelial-mesenchymal transition (EMT) in ICC. Those
      results for the first time indicate an oncogenic role of SALL4 in ICC. Therefore,
      SALL4 may serve as a promising therapeutic target for ICC. 

PMID- 26317547
TI  - Crocetinic acid inhibits hedgehog signaling to inhibit pancreatic cancer stem
      cells.
AB  - Pancreatic cancer is the fourth leading cause of cancer deaths in the US and no
      significant treatment is currently available. Here, we describe the effect of
      crocetinic acid, which we purified from commercial saffron compound crocetin
      using high performance liquid chromatography. Crocetinic acid inhibits
      proliferation of pancreatic cancer cell lines in a dose- and time-dependent
      manner. In addition, it induced apoptosis. Moreover, the compound significantly
      inhibited epidermal growth factor receptor and Akt phosphorylation. Furthermore,
      crocetinic acid decreased the number and size of the pancospheres in a dose
      dependent manner, and suppressed the expression of the marker protein DCLK-1
      (Doublecortin Calcium/Calmodulin-Dependent Kinase-1) suggesting that crocetinic
      acid targets cancer stem cells (CSC). To understand the mechanism of CSC
      inhibition, the signaling pathways affected by purified crocetinic acid were
      dissected. Sonic hedgehog (Shh) upon binding to its cognate receptor patched,
      allows smoothened to accumulate and activate Gli transcription factor. Crocetinic
      acid inhibited the expression of both Shh and smoothened. Finally, these data
      were confirmed in vivo where the compound at a dose of 0.5 mg/Kg bw suppressed
      growth of tumor xenografts. Collectively, these data suggest that purified
      crocetinic acid inhibits pancreatic CSC, thereby inhibiting pancreatic
      tumorigenesis. 

PMID- 26317548
TI  - Dietary prevention of Helicobacter pylori-associated gastric cancer with kimchi.
AB  - To prove whether dietary intervention can prevent Helicobacter pylori-induced
      atrophic gastritis and gastric cancer, we developed cancer preventive kimchi
      (cpKimchi) through special recipe and administered to chronic H. pylori
      initiated, high salt diet-promoted, gastric tumorigenesis mice model. H. pylori
      infected C57BL/6 mice were administered with cpKimchi mixed in drinking water up
      to 36 weeks. Gross and pathological gastric lesions were evaluated after 24 and
      36 weeks, respectively and explored underlying molecular changes to explain
      efficacies. Cancer preventive actions of anti-inflammation and anti-mutagenesis
      were compared between standard recipe kimchi (sKimchi) and special recipe
      cpKimchi in in vitro H. pylori-infected cell model. The erythematous and nodular
      changes, mucosal ulcerative and erosive lesions in the stomach were noted at 24th
      weeks, but cpKimchi administration significantly ameliorated. After 36th weeks,
      scattered nodular masses, some ulcers, and thin nodular gastric mucosa were noted
      in H. pylori-infected mice, whereas these gross lesions were significantly
      attenuated in cpKimchi group. On molecular analysis, significant expressions of
      COX-2 and IL-6, activated NF-kappaB and STAT3, increased apoptosis, and marked
      oxidative stresses were noted in H. pylori-infected group relevant to
      tumorigenesis, but these were all significantly attenuated in cpKimchi group.
      cpKimchi extracts imparted significant selective induction of apoptosis only in
      cancer cells, led to inhibition of H. pylori-induced proliferation, while no
      cytotoxicity through significant HO-1 induction in non-transformed gastric cells.
      In conclusion, daily dietary intake of cpKimchi can be an effective way either to
      rejuvenate H. pylori-atrophic gastritis or to prevent tumorigenesis supported
      with the concerted actions of anti-oxidative, anti-inflammatory, and anti
      mutagenic mechanisms. 

PMID- 26317549
TI  - Splenocytes derived from young WT mice prevent AD progression in APPswe/PSENldE9
      transgenic mice.
AB  - Immunosenescence contributes to pathogenesis of Alzheimer's disease (AD) in the
      elderly. In this study, we explored the effects of young wild type (WT)
      splenocytes (ySCs) on Alzheimer's disease by transplanting ySCs into
      APPswe/PSENldE9 transgenic mice. Young WT splenocytes not only prevented AD, but
      also improved the spatial learning and memory of APPswe/PSENldE9 transgenic mice.
      Young WT splenocytes enhanced Abeta clearance, decreased astrogliosis and
      increased systemic growth differentiation factor 11 (GDF11) levels. Splenocytes
      derived from old AD mouse promoted AD. There was an increased number of
      regulatory T cells (Tregs) among old AD splenocytes. We suggest that alterations
      of GDF11 and Tregs are involved in AD progression and that rejuvenation of the
      immune system is a potential therapeutic strategy in AD. 

PMID- 26317550
TI  - miR-155, identified as anti-metastatic by global miRNA profiling of a metastasis
      model, inhibits cancer cell extravasation and colonization in vivo and causes
      significant signaling alterations.
AB  - To gain insight into miRNA regulation in metastasis formation, we used a
      metastasis cell line model that allows investigation of extravasation and
      colonization of circulating cancer cells to lungs in mice. Using global miRNA
      profiling, 28 miRNAs were found to exhibit significantly altered expression
      between isogenic metastasizing and non-metastasizing cancer cells, with miR-155
      being the most differentially expressed. Highly metastatic mesenchymal-like CL16
      cancer cells showed very low miR-155 expression, and miR-155 overexpression in
      these cells lead to significantly decreased tumor burden in lungs when injected
      intravenously in immunodeficient mice. Our experiments addressing the underlying
      mechanism of the altered tumor burden revealed that miR-155-overexpressing CL16
      cells were less invasive than CL16 control cells in vitro, while miR-155
      overexpression had no effect on cancer cell proliferation or apoptosis in
      established lung tumors. To identify proteins regulated by miR-155 and thus
      delineate its function in our cell model, we compared the proteome of xenograft
      tumors derived from miR-155-overexpressing CL16 cells and CL16 control cells
      using mass spectrometry-based proteomics. >4,000 proteins were identified, of
      which 92 were consistently differentially expressed. Network analysis revealed
      that the altered proteins were associated with cellular functions such as
      movement, growth and survival as well as cell-to-cell signaling and interaction.
      Downregulation of the three metastasis-associated proteins ALDH1A1, PIR and PDCD4
      in miR-155-overexpressing tumors was validated by immunohistochemistry. Our
      results demonstrate that miR-155 inhibits the ability of cancer cells to
      extravasate and/or colonize at distant organs and brings additional insight into
      the complexity of miR-155 regulation in metastatic seeding. 

PMID- 26317551
TI  - microRNA-106b-mediated down-regulation of C1orf24 expression induces apoptosis
      and suppresses invasion of thyroid cancer.
AB  - We previously showed that C1orf24 expression is increased in thyroid carcinomas.
      Nonetheless, the mechanism underlying C1orf24 deregulation is not fully
      understood. It has been widely demonstrated that microRNAs are involved in post
      transcriptional gene regulation in several diseases, including cancer. Using in
      silico prediction approach, five microRNAs that bind to the 3'-untranslated
      region (3'-UTR) of C1orf24 were identified. The expression of two selected
      microRNAs (miR-17-5p, miR-106b) and the expression of C1orf24 were tested in 48
      benign and malignant thyroid lesions and in five thyroid carcinoma cell lines.
      miR-106b was down-regulated in thyroid cancer specimens and thyroid carcinoma
      cell lines, while C1orf24 expression was markedly increased. To demonstrate that
      miR-106b reduces C1orf24 expression, follicular (WRO) and papillary (TPC1)
      thyroid carcinoma cell lines were transiently transfected with miR-106b mimic.
      Ectopic expression of the miR-106b mimic significantly inhibits C1orf24 mRNA and
      protein expression in both WRO and TPC1 cells. Dual-luciferase report assays
      demonstrated that miR-106b directly targets C1orf24 by binding its 3'-UTR.
      Moreover, miR-106b-mediated down-regulation of C1orf24 expression increased
      apoptosis and inhibited migration. We additionally demonstrated that siRNA
      against C1orf24 significantly decreased its expression, inhibited cell migration
      and cell cycle progression while induced apoptosis. In summary, our findings not
      only provide new insights into molecular mechanism associated with C1orf24
      overexpression in thyroid carcinomas but also show that C1orf24 might increase
      proliferation and cell migration. Thus, decreasing C1orf24 levels, by restoring
      miR-106b function, may have therapeutic implications. 

PMID- 26317552
TI  - MiRNA-10a is upregulated in NSCLC and may promote cancer by targeting PTEN.
AB  - MicroRNAs (miRNAs) are involved in human cancer including non-small cell lung
      cancer (NSCLC). In this study, we compared miRNA expression microarray of SPC-A
      1sci (high metastatic) and SPC-A-1 (weakly metastatic) cells. We found that miRNA
      10a was up-regulated in NSCLC compared with corresponding normal tissues. High
      expression of miR-10a was associated with tumor node metastasis and lymph node
      metastasis. Furthermore, overexpression of miR-10a promoted NSCLC cell
      proliferation, migration and invasion in vitro. We found that PTEN was a direct
      target of miR-10a in NSCLC. Also miR-10a activated the PTEN/AKT/ERK pathway. We
      suggest that miR-10a contributes to NSCLC by targeting PTEN. 

PMID- 26317553
TI  - Identification and characterization of ANO9 in stage II and III colorectal
      carcinoma.
AB  - BACKGROUND AND OBJECTIVES: The precise role and potential underlying mechanisms
      of anoctamin 9 (ANO9) remain largely unknown. This study aims to characterize the
      role and oncogenic mechanisms of ANO9 in stage II and III colorectal cancer
      (CRC). METHODS: We examined the expression of ANO9 in colorectal cancerous
      tissues and cells using real-time quantitative PCR and immunohistochemistry,
      respectively. Multiple cellular and molecular approaches such as gene
      transfection, CCK-8 assay, flow cytometry, and invasion assay were also performed
      to explore its oncogenic mechanisms. Furthermore, the clinical significance of
      ANO9 in clinical CRC specimens was assessed by clinical correlation and survival
      analyses. RESULTS: Lower expression of ANO9 messenger RNA (mRNA) was frequently
      detected both in CRC tissues with recurrence and metastasis-derived cell lines.
      Compared with matched nontumorous tissues, lower expression of ANO9 protein was
      observed in tumors, which was significantly correlated with tumorigenesis (p <
      0.05). In vitro functional studies showed that ANO9 contributed to tumor cell
      proliferation, apoptosis, and invasion. Moreover, investigation of clinical CRC
      specimens showed that ANO9 were markedly overexpressed in metastatic tissue
      compared with primary tissue. Decreased expression of ANO9 was correlated with
      poor prognostic outcomes. CONCLUSIONS: This study highlighted the role of ANO9 in
      progression and metastasis of stage II and III CRC. These findings suggested that
      up-regulation of ANO9, as a metastasis-related gene, could be a novel approach
      for inhibiting CRC progression.

PMID- 26317554
TI  - The Cortisol Paradox of Trauma-Related Disorders: Lower Phasic Responses but
      Higher Tonic Levels of Cortisol Are Associated with Sexual Abuse in Childhood.
AB  - OBJECTIVES: Inconsistent findings exist for the activity of the hypothalamic
      pituitary-adrenal (HPA) axis in patients with stress related disorders. Recent
      studies point towards early life stress as a potential modulator. METHODS: We
      investigated the impact of childhood sexual abuse on phasic (saliva cortisol
      reactivity) and tonic (hair cortisol) regulation. Furthermore, we assessed
      predictors on cortisol accumulation in hair. Women (N = 43) with stress-related
      disorders underwent a standardized assessment of idiographic adverse and
      traumatic experiences and psychopathology, while measuring salivary cortisol and,
      heart rate and blood pressure. RESULTS: Comparing women with and without
      childhood sexual abuse revealed lower rates of responders and distinct levels of
      salivary cortisol to the interview in conjunction with a lower heart rate for the
      abused group. Childhood adversities, traumatic experiences, and depression
      contributed to higher hair cortisol levels. CONCLUSIONS: Our finding of lower
      response rate and distinct salivary cortisol pattern in individuals with
      childhood sexual abuse compared to individuals without early sexual abuse
      supports the role of environmental programming for the HPA axis. Both, childhood
      adversities and traumatic stress emerge as crucial factors for long-term cortisol
      secretion. Lower or suppressed phasic cortisol responses to trauma-related
      stimuli may therefore be associated with higher tonic values. Thus, early
      exposure to adversities may result in a biological distinct phenotype in adult
      patients with stress-related disorders.

PMID- 26317555
TI  - Influence of a Decaying Cyclonic Eddy on Biogenic Silica and Particulate Organic
      Carbon in the Tropical South China Sea Based on 234Th-238U Disequilibrium.
AB  - Eddies play a critical role in regulating the biological pump by pumping new
      nutrients to the euphotic zone. However, the effects of cyclonic eddies on
      particle export are not well understood. Here, biogenic silica (BSi) and
      particulate organic carbon (POC) exports were examined inside and outside a
      decaying cyclonic eddy using 234Th-238U disequilibria in the tropical South China
      Sea. For the eddy and outside stations, the average concentrations of BSi in the
      euphotic zone were 0.17+/-0.09 MUmol L-1 (mean+/-sd, n = 20) and 0.21+/-0.06
      MUmol L-1 (n = 34). The POC concentrations were 1.42+/-0.56 MUmol L-1 (n = 34)
      and 1.30+/-0.46 MUmol L-1 (n = 51). Both BSi and POC abundances did not show
      change at the 95% confidence level. Based on the 234Th-238U model, BSi export
      fluxes in the eddy averaged 0.18+/-0.15 mmol Si m-2 d-1, which was comparable
      with the 0.40+/-0.20 mmol Si m-2 d-1 outside the eddy. Similarly, the average POC
      export fluxes were 1.5+/-1.4 mmol C m-2 d-1 and 1.9+/-1.3 mmol C m-2 d-1 for the
      eddy and outside stations. From these results we concluded that cyclonic eddies
      in their decaying phase have little effect on the abundance and export of
      biogenic particles. 

PMID- 26317556
TI  - Evening typology and morning tiredness associates with low leisure time physical
      activity and high sitting.
AB  - Circadian typology is a latent trait that is usually assessed with scoring on a
      series of questions thought to represent the construct. But, in the
      classification, most people fall into the intermediate type, i.e. neither a
      definite morning nor an evening type, but still showing stronger preference
      towards either end of the continuum. Our aim was to operationalize chronotype
      using latent class analysis (LCA) for a 6-item scale derived from the original
      Horne-Ostberg Morningness-Eveningness Questionnaire to compare and understand
      characteristics of chronotype in a population-based sample of adults in Finland.
      A total of 4904 men and women aged 25-74 years were included. We also analyzed
      the associations of chronotypes with physical activity (PA) and sitting. We found
      five latent chronotype groups including "rested more-evening type" (28%), "rested
      more-morning type" (24%), "morning type" (23%), "tired more-evening type" (17%)
      and "evening type" (8%) groups. Operationalization of chronotype by LCA suggests
      that morning alertness is an important feature differentiating chronotypes.
      Further, the "evening type" and the "tired, more-evening type" had higher odds
      for none to very low as well as low PA, as compared to "morning type". In
      addition, "evening type" was associated with higher odds for more time spent
      sitting, as compared to "morning type". Our findings indicate that it is
      important to assess sleep schedules and morning tiredness, which then could be
      targeted as a potential mediating factor for health behaviors, in particular, PA
      and health status. 

PMID- 26317557
TI  - 1-Methyl Naphthalene Reorientation at the Air-Liquid Interface upon Water
      Saturation Studied by Vibrational Broad Bandwidth Sum Frequency Generation
      Spectroscopy.
AB  - Vibrational broad bandwidth sum frequency generation spectroscopy was employed to
      investigate the surface structure of neat 1-methyl naphthalene (1-MN) and the
      reorientation of the 1-MN molecules upon saturation of the 1-MN liquid with
      water. The neat 1-MN liquid molecules have their aromatic rings aligned
      antiparallel to one another with their methyl groups alternating out of the
      surface and into the subsurface region from molecule to molecule. With the
      introduction of relatively few water molecules into the 1-MN liquid (1:336
      water/1-MN) a rearrangement of the surface molecules is induced, leading to an
      increased number density of the methyl groups arranged such that more methyl
      groups are oriented in the same direction into the air phase at the air-liquid 1
      MN interface. Surface tension measurements reveal an increase in the surface
      tension upon water saturation of the 1-MN liquid, indicating surface activity of
      the water in the 1-MN solution. It is also clear that the reorientation of the
      surface 1-MN molecules is reversible. 

PMID- 26317558
TI  - Flaxseed Protects Against Diabetes-Induced Glucotoxicity by Modulating Pentose
      Phosphate Pathway and Glutathione-Dependent Enzyme Activities in Rats.
AB  - This study investigated the effects of flaxseed (Linum usitatissimum L.) intake
      on general metabolism, pentose phosphate pathway (PPP) and glutathione-dependent
      enzymes in diabetic rats. Diabetes was induced by streptozotocin injection (40
      mg/kg, i.p.) and the enzyme activities were determined spectrophotometrically.
      Diabetic and control rats were divided in two subgroups, one untreated, and one
      treated with flaxseed (0.714 g/kg body weight/day; orally) for 12 weeks. Flaxseed
      ameliorated decreased body weight (p < .05) and increased blood glucose (p <
      .001), triglyceride (p < .001), ALT (p < .001) and AST (p < .001) in diabetic
      rats. Diabetes resulted in increased glucose-6-phosphate dehydrogenase (G6PD) (p
      < .05) and decreased glutathione-S-transferase (GST) (p < .01), but unchanged 6
      phosphogluconate dehydrogenase (6PGD) and glutathione reductase (GR) in the brain
      of rats. These alterations were partially improved by flaxseed in comparison to
      diabetic untreated group (p < .05). G6PD, 6PGD, GR were elevated (p < .001),
      while GST unchanged in the lung of diabetic untreated group compared to control.
      Flaxseed partially prevented the increase in 6PGD (p < .05) and GR (p < .01), but
      unaffected G6PD in the lung of diabetic rats. G6PD (p < .001), 6PGD (p < .05), GR
      (p < .001) were augmented, while GST showed a significant (p < .001) depletion in
      the pancreas of diabetic untreated rats compared to control. Diabetic alterations
      observed in pancreatic enzyme activities were significantly prevented by
      flaxseed. Furthermore, a remarkable decrease in 6PGD (p < .001) and an increase
      in G6PD (threefold of control) were found in the lens of diabetic untreated group
      that were completely prevented by flaxseed (p < .001). Flaxseed has beneficial
      effects against diabetes-induced glucotoxicity by modulating G6PD, 6PGD, GR and
      GST activities in tissues.

PMID- 26317559
TI  - HLA Markers DQ8 and DR53 Are Associated With Lymphocytic Hypophysitis and May Aid
      in Differential Diagnosis.
AB  - IMPORTANCE: Lymphocytic hypophysitis (LH) is a poorly understood autoimmune
      disorder of the pituitary gland. Symptoms include headache, pituitary
      dysfunction, visual disturbances, and neurological deficits. The diagnosis can be
      made based on clinical and biochemical findings, but for atypical presentations,
      no circulatory diagnostic biomarkers exist, and a pituitary biopsy is necessary
      for diagnosis. OBJECTIVES: We used high-resolution human leukocyte antigen (HLA)
      screening assays to investigate a relationship between specific HLA markers and
      LH. DESIGN: This was a retrospective analysis. SETTING: The study was conducted
      at a tertiary referral center. SUBJECTS: Fifteen patients with sporadic LH, 4
      patients with melanoma who developed hypophysitis after administration of
      cytotoxic T lymphocyte antigen 4 (CTLA4) antibodies, and 1 patient with sarcoid
      associated hypophysitis were evaluated. INTERVENTION: Clinical data, including
      endocrine function, were assessed, and HLA typing was performed in all 20
      patients with hypophysitis, 50 control patients with other sellar abnormalities,
      and 4 CTLA4 antibody-treated patients without hypophysitis. RESULTS: Two major
      histocompatibility class II HLA markers, DQ8 and DR53, were found in 13 of 15
      (87%) and 12 of 15 (80.0%) patients with sporadic LH, respectively. In contrast,
      none of the 4 patients who developed hypophysitis after administration of the
      CTLA4 antibodies exhibited the HLA-DQ8 marker and only 1 of 4 (25%) exhibited the
      HLA-DR53 marker. In a parallel group of 50 control subjects with sellar masses
      and 4 CTLA4 antibody-treated patients who did not develop evidence of pituitary
      failure, the candidate HLA subtypes were found in ~20% for DQ8 and ~48% for DR53,
      respectively. CONCLUSION AND RELEVANCE: The HLA markers, DQ8 and DR53, were found
      to be commonly present in patients with LH. The odds ratio of a patient with LH
      expressing the HLA-DQ8 marker is 23.1-fold higher than that of a patient with
      another sellar mass. HLA-DQ8 testing may assist in diagnosis and avoid
      unnecessary biopsies in patients with atypical LH.

PMID- 26317560
TI  - Bioavailable Vitamin D in Obese Children: The Role of Insulin Resistance.
AB  - CONTEXT: Studies examining vitamin D levels in association with childhood obesity
      usually do not consider the effect of insulin on vitamin D-binding protein and do
      not calculate the unbound, bioavailable vitamin D. OBJECTIVE: This study aimed to
      evaluate in a group of children 1) the concentrations of both total 25
      hydroxyvitamin D and bioavailable fraction, and 2) the potential role of insulin
      resistance in modulating the concentrations of bioavailable vitamin D. Design,
      Setting, and Patients or Other Participants: This was a cross-sectional study at
      a University Pediatric Department in which 63 obese children and 21 lean controls
      were enrolled. MAIN OUTCOME MEASURES: Total 25-hydroxyvitamin D and vitamin D
      binding protein were measured, two single-nucleotide polymorphisms in the coding
      region of the vitamin D-binding protein (rs4588 and rs7041) were studied, and the
      vitamin D bioavailable fraction was calculated. RESULTS: Obese children showed
      total 25-hydroxyvitamin D levels lower compared with nonobese children (21.3 +/-
      6.7 ng/mL vs 29.6 +/- 11.7 ng/mL; P = .0004). Bioavailable 25-hydroxyvitamin D
      levels were not different among the two groups (3.1 +/- 1.6 ng/mL vs 2.6 +/- 1.2
      ng/mL; P > .05). Insulin-resistant children showed higher bioavailable levels of
      25-hydroxyvitamin D compared with noninsulin-resistant children (3.4 +/- 1.4
      ng/mL vs 2.0 +/- 0.9 ng/mL; P = .013) and an inverse correlation between insulin
      resistance and vitamin D-binding protein was found (r:= -0.40; P = .024).
      CONCLUSIONS: Obese children present levels of bioavailable 25-hydroxyvitamin D
      similar to those of normal-weight children due to reduced concentration of
      vitamin D-binding protein. The insulin resistance could play a role in this
      reduced concentration.

PMID- 26317561
TI  - The Association of Salvia divinorum and Psychotic Disorders: A Review of the
      Literature and Case Series.
AB  - The association of substance abuse and psychotic disorders is of interest to
      clinicians, academics, and lawmakers. Commonly abused substances, such as
      cannabis, cocaine, amphetamines, and alcohol, have all been associated with
      substance-induced psychosis. Hallucinogens can induce desired psychedelic effects
      and undesirable psychomimetic reactions. These are usually transient and resolve
      once the duration of action is over. Sometimes, these effects persist, causing
      distress and requiring intervention. This article focuses on the hallucinogenic
      substance Salvia divinorum, the use of which has been observed, particularly
      among youth worldwide. We present background information based on a review of the
      literature and on our own clinical encounters, as highlighted by two original
      case reports. We hypothesize that consumption of Salvia divinorum could be
      associated with the development of psychotic disorders. We propose that
      clinicians routinely inquire about the use of Salvia in patients with substance
      use disorders or psychotic illnesses. More research is required to assess any
      relationship between Salvia divinorum and psychosis. Additionally, we advocate
      increased public and medical awareness of this substance and other emerging drugs
      of abuse. 

PMID- 26317562
TI  - Automatic detection of cirrhosis in hospitalized patients: a pragmatic
      experience.
AB  - BACKGROUND/AIM: We evaluated the relevance of a systematic automatic detection of
      cirrhosis using biochemical markers in hospitalized patients. METHODS: We
      automatically calculated three free biochemical tests (APRI, Fib-4, and Forns) in
      patients consecutively hospitalized in our university hospital between July and
      September, 2010. Patients >18 years not known to suffer from chronic liver
      disease, were contacted to undergo liver stiffness measurement (LSM) as a
      reference diagnostic tool. To limit false positives, we required at least one
      APRI>=2 (indicating cirrhosis) and Fib-4>3.25 and/or Forns>6.9, without obvious
      overestimation. RESULTS: A total of 10,035 APRI, 9903 Fib-4, and 1250 Forns were
      available in 4074 patients. The fibrosis tests were independently influenced by
      the location of the patient, especially Cardiology (Lower Forns) and
      Hematology/Oncology Departments (higher APRI, Fib-4, and Forns). Overall, 101
      patients (2.48%) were suspected to have cirrhosis. LSM identified two cases of
      cirrhosis (LSM>13 kPa). In intent-to-diagnose analyses, the highest positive
      predictive values of the APRI, Fib-4, and Forns for the diagnosis of cirrhosis
      were 1.98, 1.98, and 11.76%, respectively. The positive predictive value never
      exceeded 50% in per-protocol analyses when considering patients with numerous
      positive results of the fibrosis tests. CONCLUSION: In hospitalized patients,
      automatic detection of cirrhosis on the basis of APRI, Fib-4, and Forns was
      inefficient because of too many false-positive results.

PMID- 26317563
TI  - Biomarker Analysis of Samples Visually Identified as Microbial in the Eocene
      Green River Formation: An Analogue for Mars.
AB  - One of the major exploration targets for current and future Mars missions are
      lithofacies suggestive of biotic activity. Although such lithofacies are not
      confirmation of biotic activity, they provide a way to identify samples for
      further analyses. To test the efficacy of this approach, we identified carbonate
      samples from the Eocene Green River Formation as "microbial" or "non-microbial"
      based on the macroscale morphology of their laminations. These samples were then
      crushed and analyzed by gas chromatography/mass spectroscopy (GC/MS) to determine
      their lipid biomarker composition. GC/MS analysis revealed that carbonates
      visually identified as "microbial" contained a higher concentration of more
      diverse biomarkers than those identified as "non-microbial," suggesting that this
      could be a viable detection strategy for selecting samples for further analysis
      or caching on Mars.

PMID- 26317564
TI  - Re: "comparison of in-hospital morbidity and mortality rates between anterior and
      nonanterior approach procedures for thoracic disc herniation" by Yoshihara et al.

PMID- 26317565
TI  - Comparison of in-hospital morbidity and mortality rates between anterior and
      nonanterior approach procedures for thoracic disc herniation" by Yoshihara et al.

PMID- 26317567
TI  - Posttraumatic Propofol Neurotoxicity Is Mediated via the Pro-Brain-Derived
      Neurotrophic Factor-p75 Neurotrophin Receptor Pathway in Adult Mice.
AB  - OBJECTIVES: The gamma-aminobutyric acid modulator propofol induces neuronal cell
      death in healthy immature brains by unbalancing neurotrophin homeostasis via p75
      neurotrophin receptor signaling. In adulthood, p75 neurotrophin receptor becomes
      down-regulated and propofol loses its neurotoxic effect. However, acute brain
      lesions, such as traumatic brain injury, reactivate developmental-like programs
      and increase p75 neurotrophin receptor expression, probably to foster reparative
      processes, which in turn could render the brain sensitive to propofol-mediated
      neurotoxicity. This study investigates the influence of delayed single-bolus
      propofol applications at the peak of p75 neurotrophin receptor expression after
      experimental traumatic brain injury in adult mice. DESIGN: Randomized laboratory
      animal study. SETTING: University research laboratory. SUBJECTS: Adult C57BL/6N
      and nerve growth factor receptor-deficient mice. INTERVENTIONS: Sedation by IV
      propofol bolus application delayed after controlled cortical impact injury.
      MEASUREMENTS AND MAIN RESULTS: Propofol sedation at 24 hours after traumatic
      brain injury increased lesion volume, enhanced calpain-induced alphaII-spectrin
      cleavage, and increased cell death in perilesional tissue. Thirty-day postinjury
      motor function determined by CatWalk (Noldus Information Technology, Wageningen,
      The Netherlands) gait analysis was significantly impaired in propofol-sedated
      animals. Propofol enhanced pro-brain-derived neurotrophic factor/brain-derived
      neurotrophic factor ratio, which aggravates p75 neurotrophin receptor-mediated
      cell death. Propofol toxicity was abolished both by pharmacologic inhibition of
      the cell death domain of the p75 neurotrophin receptor (TAT-Pep5) and in mice
      lacking the extracellular neurotrophin binding site of p75 neurotrophin receptor.
      CONCLUSIONS: This study provides first evidence that propofol sedation after
      acute brain lesions can have a deleterious impact and implicates a role for the
      pro-brain-derived neurotrophic factor-p75 neurotrophin receptor pathway. This
      observation is important as sedation with propofol and other compounds with GABA
      receptor activity are frequently used in patients with acute brain pathologies to
      facilitate sedation or surgical and interventional procedures.

PMID- 26317568
TI  - Excellent Outcome With Extracorporeal Membrane Oxygenation After Accidental
      Profound Hypothermia (13.8 degrees C) and Drowning.
AB  - OBJECTIVE: To report outcome and intensive care strategy in a 7-year-old girl
      with accidental profound hypothermia and drowning. DATA SOURCES AND EXTRACTION:
      Patient records and interviews with search-and-rescue personnel. STUDY SELECTION:
      Case report. DATA SYNTHESIS: The girl was rescued after an estimated submersion
      time of at least 83 minutes in icy sea water. She presented with cardiac arrest,
      ice in her upper airways, a first-documented nasopharyngeal temperature of 13.8
      degrees C, and a serum potassium of 11.3 mmol/L. The patient was slowly rewarmed
      with extracorporeal membrane oxygenation and made an exceptional recovery after
      intensive care and a long rehabilitation time. CONCLUSION: Excellent outcome is
      possible in children with body temperature and serum potassium reaching the far
      limits of previously reported human survival and prolonged submersion time.

PMID- 26317569
TI  - Outcomes Associated With the Nationwide Introduction of Rapid Response Systems in
      The Netherlands.
AB  - OBJECTIVE: To describe the effect of implementation of a rapid response system on
      the composite endpoint of cardiopulmonary arrest, unplanned ICU admission, or
      death. DESIGN: Pragmatic prospective Dutch multicenter before-after trial, Cost
      and Outcomes analysis of Medical Emergency Teams trial. SETTING: Twelve hospitals
      participated, each including two surgical and two nonsurgical wards between April
      2009 and November 2011. The Modified Early Warning Score and Situation-Background
      Assessment-Recommendation instruments were implemented over 7 months. The rapid
      response team was then implemented during the following 17 months. The effects of
      implementing the rapid response team were measured in the last 5 months of this
      period. PATIENTS: All patients 18 years old and older admitted to the study wards
      were included. MEASUREMENTS AND MAIN RESULTS: In total, 166,569 patients were
      included in the study representing 1,031,172 hospital admission days. No
      differences were observed in patient demographics between periods. The composite
      endpoint of cardiopulmonary arrest, unplanned ICU admission, or death per 1,000
      admissions was significantly reduced in the rapid response team versus the before
      phase (adjusted odds ratio, 0.847; 95% CI, 0.725-0.989; p = 0.036).
      Cardiopulmonary arrests and in-hospital mortality were also significantly reduced
      (odds ratio, 0.607; 95% CI, 0.393-0.937; p = 0.018 and odds ratio, 0.802; 95% CI,
      0.644-1.0; p = 0.05, respectively). Unplanned ICU admissions showed a declining
      trend (odds ratio, 0.878; 95% CI, 0.755-1.021; p = 0.092), whereas severity of
      illness at the moment of ICU admission was not different between periods.
      CONCLUSIONS: In this study, introduction of nationwide implementation of rapid
      response systems was associated with a decrease in the composite endpoint of
      cardiopulmonary arrests, unplanned ICU admissions, and mortality in patients in
      general hospital wards. These findings support the implementation of rapid
      response systems in hospitals to reduce severe adverse events.

PMID- 26317570
TI  - High-Frequency Oscillatory Ventilation in Pediatric Acute Lung Injury: A
      Multicenter International Experience.
AB  - OBJECTIVE: We aim to describe current clinical practice, the past decade of
      experience and factors related to improved outcomes for pediatric patients
      receiving high-frequency oscillatory ventilation. We have also modeled predictive
      factors that could help stratify mortality risk and guide future high-frequency
      oscillatory ventilation practice. DESIGN: Multicenter retrospective,
      observational questionnaire study. SETTING: Seven PICUs. PATIENTS: Demographic,
      disease factor, and ventilatory and outcome data were collected, and 328 patients
      from 2009 to 2010 were included in this analysis. INTERVENTIONS: None.
      MEASUREMENT AND MAIN RESULTS: Patients were classified into six cohorts based on
      underlying diagnosis. We used univariate analysis to identify factors associated
      with mortality risk and multivariate logistic regression to identify independent
      predictors of mortality risk. An oxygenation index greater than 35 and
      immunocompromise exhibited the greatest predictive power (p < 0.0001) for
      increased mortality risk, and respiratory syncytial virus was associated with
      lowest mortality risk (p = 0.003). Differences in mortality risk as a function of
      oxygenation index were highly dependent on primary underlying condition. A trend
      toward an increase in oscillator amplitude and frequency was observed when
      compared with historical data. CONCLUSIONS: Given the number of centers and
      subjects included in the database, these findings provide a robust description of
      current practice regarding the use of high-frequency oscillatory ventilation for
      pediatric hypoxic respiratory failure. Patients with severe hypoxic respiratory
      failure and immunocompromise had the highest mortality risk, and those with
      respiratory syncytial virus had the lowest. A means of identifying the risk of 30
      day mortality for subjects can be obtained by identifying the underlying disease
      and oxygenation index on conventional ventilation preceding the initiation of
      high-frequency oscillatory ventilation.

PMID- 26317572
TI  - Multiple-Timestep ab Initio Molecular Dynamics Using an Atomic Basis Set
      Partitioning.
AB  - This work describes an approach to accelerate ab initio Born-Oppenheimer
      molecular dynamics (MD) simulations by exploiting the inherent timescale
      separation between contributions from different atom-centered Gaussian basis
      sets. Several MD steps are propagated with a cost-efficient, low-level basis set,
      after which a dynamical correction accounts for large basis set relaxation
      effects in a time-reversible fashion. This multiple-timestep scheme is shown to
      generate valid MD trajectories, on the basis of rigorous testing for water
      clusters, the methanol dimer, an alanine polypeptide, protonated hydrazine, and
      the oxidized water dimer. This new approach generates observables that are
      consistent with those of target basis set trajectories, including MD-based
      vibrational spectra. This protocol is shown to be valid for Hartree-Fock, density
      functional theory, and second-order Moller-Plesset perturbation theory
      approaches. Recommended pairings include 6-31G as a low-level basis set for 6
      31G** or 6-311G**, as well as cc-pVDZ as the subset for accurate dynamics with
      aug-cc-pVTZ. Demonstrated cost savings include factors of 2.6-7.3 on the systems
      tested and are expected to remain valid across system sizes. 

PMID- 26317571
TI  - IV Immunoglobulin for Acute Lung Injury and Bacteremia in Pseudomonas aeruginosa
      Pneumonia.
AB  - OBJECTIVES: Virulent and multidrug-resistant Pseudomonas aeruginosa causes a
      lethal pneumonia, especially in patients who are artificially ventilated. It has
      been reported that the virulence mechanism used by P. aeruginosa, which is linked
      to acute lung injury, is strongly associated with the type III secretion system,
      and specific antibodies targeting this system have shown a protective effect in
      both experimental and clinical settings. We investigated the effect of
      administering IV immunoglobulins on P. aeruginosa pneumonia, including its
      associated bacteremia and mortality, although focusing especially on type III
      secretion system-associated P. aeruginosa virulence. DESIGN: Prospective
      randomized and controlled animal study. SETTING: University laboratory. SUBJECTS:
      Male ICR mice. INTERVENTIONS: Mice were infected intratracheally with a lethal
      dose of the virulent P. aeruginosa PA103 strain. IV immunoglobulin administration
      was examined in three different settings: 1) premixed; 2) pre-IV, prophylactic
      administration before bacterial infection; and 3) post-IV, therapeutic
      administration after bacterial infection. The effect of specific antigen titer
      depletion of IV immunoglobulins was also examined. MEASUREMENTS AND MAIN RESULTS:
      Survival and body temperature were monitored for 24 hours. Bacteremia, cytokine
      concentration, myeloperoxidase activity, WBC counts in the blood, and lung
      bacterial load were evaluated. Survival improved significantly in mice that
      received IV immunoglobulins (p < 0.05). Lung edema, lung bacteriologic load, and
      bacteremia decreased significantly in the IV immunoglobulin-treated mice (p <
      0.05). The mechanism of protection was associated with the presence of antibodies
      against both PcrV and some bacterial surface antigens in the IV immunoglobulins.
      CONCLUSIONS: IV immunoglobulin administration had a significantly protective
      effect against lethal infection from virulent P. aeruginosa. Prophylactic IV
      immunoglobulin administration at the highest dose was comparable with that
      achieved by administrating a specific anti-PcrV polyclonal IgG into the mice. The
      mechanism of protection is likely to involve the synergic action of anti-PcrV
      titers and antibodies against some surface antigen(s) that block the type III
      secretion system-associated virulence of P. aeruginosa.

PMID- 26317574
TI  - Distraction Osteogenesis Using Bone Matrix Osteotensors in Ectodermal Dysplasia:
      A Case Report.
AB  - INTRODUCTION: Ectodermal dysplasia patients require complex oral rehabilitation.
      Bone matrix Osteotensors activate the patient's own stem cells to promote new
      bone formation through an autogenous growth factor cascade generated by a
      targeted flapless bone distraction before implant and/or bone graft therapy.
      MATERIALS AND METHODS: The maxillary and mandibular bone were activated 21 (for
      type I bone) to 45 days (for type IV bone) before implant and/or bone substitute
      installation. Purpose-designed Osteotensors initiated massive recruitment of stem
      cells in the intended bone recipient site, thereby triggering neoangiogenesis and
      osteogenesis. After new bone formation, root-form implants and Diskimplants were
      installed. Functional loading was obtained at 48 hours using highly rigid, screw
      secured fixed upper and lower full-arch prostheses. RESULTS: At 3 years, all
      implants appeared clinically and radiologically osseointegrated with an excellent
      functional and esthetic outcome. CONCLUSION: Flapless distraction osteogenesis
      using bone matrix Osteotensors several weeks before surgery improved the initial
      quality and volume of the recipient bone bed. This minimally invasive approach
      allows future successful immediate implant-supported complete maxillomandibular
      fixed rehabilitation without preliminary grafting procedures in patients with an
      unfavorable initial bone anatomy.

PMID- 26317573
TI  - Innate Lymphoid Cells Groups 1 and 3 in the Epithelial Compartment of Functional
      Human Intestinal Allografts.
AB  - We examined intraepithelial lymphocytes (IELs) in 213 ileal biopsies from 16
      bowel grafts and compared them with 32 biopsies from native intestines. During
      the first year posttransplantation, grafts exhibited low levels of IELs
      (percentage of CD103(+) cells) principally due to reduced CD3(+) CD8(+) cells,
      while CD103(+) CD3(-) cell numbers became significantly higher. Changes in IEL
      subsets did not correlate with histology results, isolated intestine, or
      multivisceral transplants, but CD3(-) IELs were significantly higher in patients
      receiving corticosteroids. Compared with controls, more CD3(-) IELs of the grafts
      expressed CD56, NKp44, interleukin (IL)-23 receptor, retinoid-related orphan
      receptor gamma t (RORgammat), and CCR6. No difference was observed in granzyme B,
      and CD3(-) CD127(+) cells were more abundant in native intestines. Ex vivo, and
      after in vitro activation, CD3(-) IELs in grafts produced significantly more
      interferon (IFN)-gamma and IL-22, and a double IFNgamma(+) IL-22(+) population
      was observed. Epithelial cell-depleted grafts IELs were cytotoxic, whereas this
      was not observed in controls. In conclusion, different from native intestines, a
      CD3(-) IEL subset predominates in grafts, showing features of natural killer
      cells and intraepithelial ILC1 (CD56(+) , NKp44(+) , CCR6(+) , CD127(-) ,
      cytotoxicity, and IFNgamma secretion), ILC3 (CD56(+) , NKp44(+) , IL-23R(+) ,
      CCR6(+) , RORgammat(+) , and IL-22 secretion), and intermediate ILC1-ILC3
      phenotypes (IFNgamma(+) IL-22(+) ). Viability of intestinal grafts may depend on
      the balance among proinflammatory and homeostatic roles of ILC subsets. 

PMID- 26317575
TI  - Removal Rates of Dental Implants Placed in Conjunction With Autologous Bone and
      Xenogeneic and Synthetic Alloplastic Materials in Finland Between 1994 and 2012.
AB  - PURPOSE: This study aimed to assess the use of bone augmentation materials in
      Finland from 1994 to 2012 by assessing removal rates of implants placed in
      combination with autologous bone, xenogeneic grafts, and synthetic alloplastic
      materials. MATERIALS AND METHODS: The National Institute for Health and Welfare
      in Finland granted permission to access raw data of the Finnish Dental Implant
      Register for implant augmentation materials and removal rates of implants placed
      in augmented sites from April 1994 to April 2012. RESULTS: A total of 198,538
      implants were placed in Finland between 1994 and 2012 in 110,543 operations. A
      total of 3318 (1.7%) of the placed implants were removed during the observation
      period. Augmentations were performed on 20,812 (18.8%) operations during 1994
      2012. The removal rates of implants placed at sites augmented with autologous
      bone were 2.31%, xenogeneic materials 0.91%, and synthetic alloplastic materials
      2.80%. The removal rate was 1.87% when no augmentation material was used.
      CONCLUSIONS: The placement of dental implants in conjunction with bone
      augmentation materials is predictable with a low complication rate.

PMID- 26317576
TI  - Near-Infrared Spatially Resolved Spectroscopy for Tablet Quality Determination.
AB  - Near-infrared (NIR) spectroscopy has become a well-established tool for the
      characterization of solid oral dosage forms manufacturing processes and finished
      products. In this work, the utility of a traditional single-point NIR measurement
      was compared with that of a spatially resolved spectroscopic (SRS) measurement
      for the determination of tablet assay. Experimental designs were used to create
      samples that allowed for calibration models to be developed and tested on both
      instruments. Samples possessing a poor distribution of ingredients (highly
      heterogeneous) were prepared by under-blending constituents prior to compaction
      to compare the analytical capabilities of the two NIR methods. The results
      indicate that SRS can provide spatial information that is usually obtainable only
      through imaging experiments for the determination of local heterogeneity and
      detection of abnormal tablets that would not be detected with single-point
      spectroscopy, thus complementing traditional NIR measurement systems for in-line,
      and in real-time tablet analysis.

PMID- 26317577
TI  - A Novel Allyl Transfer Coupled with a Grob Fragmentation.
AB  - A novel acid-promoted rearrangement is disclosed. In the previously unknown
      transformation, an allyl group migrated to an in situ formed carbocation
      stabilized by an electron-rich aryl or heteroaryl group, resulting in a
      stereoselective intramolecular Grob fragmentation. The outcome of the
      rearrangement observed with an array of substrates can be satisfactorily
      rationalized using a working hypothesis with the aid of a six-membered transition
      state similar to those proposed for the anionic oxy-Cope or oxonia-Cope
      rearrangements, but involving only one instead of two double bonds. 

PMID- 26317579
TI  - Comparing the performance of FAM19A4 methylation analysis, cytology and HPV16/18
      genotyping for the detection of cervical (pre)cancer in high-risk HPV-positive
      women of a gynecologic outpatient population (COMETH study).
AB  - Recently, DNA methylation analysis of FAM19A4 in cervical scrapes has been shown
      to adequately detect high-grade cervical intraepithelial neoplasia and cervical
      cancer (>= CIN3) in high-risk HPV (hrHPV)-positive women. Here, we compared the
      clinical performance of FAM19A4 methylation analysis to cytology and HPV16/18
      genotyping, separately and in combination, for >= CIN3 detection in hrHPV
      positive women participating in a prospective observational multi-center cohort
      study. The study population comprised hrHPV-positive women aged 18-66 years,
      visiting a gynecological outpatient clinic. From these women, cervical scrapes
      and colposcopy-directed biopsies (for histological confirmation) were obtained.
      Cervical scrapes were analyzed for FAM19A4 gene promoter methylation, cytology
      and HPV16/18 genotyping. Methylation analysis was performed by quantitative
      methylation-specific PCR (qMSP). Sensitivities and specificities for >= CIN3 were
      compared between tests. Stratified analyses were performed for variables that
      potentially influence marker performance. Of all 508 hrHPV-positive women, the
      sensitivities for >= CIN3 of cytology, FAM19A4 methylation analysis, and cytology
      combined with HPV16/18 genotyping were 85.6, 75.6 and 92.2%, respectively, with
      corresponding specificities of 49.8, 71.1 and 29.4%, respectively. Both
      sensitivity and specificity of FAM19A4 methylation analysis were associated with
      age (p <= 0.001 each). In women >= 30 years (n = 287), >= CIN3 sensitivity of
      FAM19A4 methylation analysis was 88.3% (95%CI: 80.2-96.5) which was noninferior
      to that of cytology [85.5% (95%CI: 76.0-94.0)], at a significantly higher
      specificity [62.1% (95%CI: 55.8-68.4) compared to 47.6% (95%CI: 41.1-54.1)]. In
      conclusion, among hrHPV-positive women from an outpatient population aged >= 30
      years, methylation analysis of FAM19A4 is an attractive marker for the
      identification of women with >= CIN3.

PMID- 26317580
TI  - Identifying Risk for Self-Harm: Rumination and Negative Affectivity in the
      Prospective Prediction of Nonsuicidal Self-Injury.
AB  - Research suggests nonsuicidal self-injury (NSSI) may function as a maladaptive
      strategy to regulate negative emotions, and individuals high in trait negative
      affectivity (NA) may be particularly at risk. Rumination, a cognitive emotion
      regulation strategy, may amplify negative affect, increasing the likelihood of
      NSSI. The current study found that high NA and high rumination interacted to
      predict both likelihood of engagement in NSSI and frequency of NSSI. This study
      provides support for the joint contribution of cognitive and temperamental
      factors impacting the relationship between NA and NSSI and suggests that
      interventions targeted at maladaptive emotion regulation strategies may help
      inform individualized treatment. 

PMID- 26317582
TI  - A novel colorimetric assay of beta-D-glucans in basidiomycete strains by alcian
      blue dye in a 96-well microtiter plate.
AB  - Basidiomycete strains synthesize several types of beta-d-glucans, which play a
      major role in the medicinal properties of mushrooms. Therefore, the specific
      quantification of these beta-d-glucans in mushroom strains is of great
      biochemical importance. Because published assay methods for these beta-d-glucans
      present some disadvantages, a novel colorimetric assay method for beta-d-glucan
      with alcian blue dye was developed. The complex formation was detected by
      following the decrease in absorbance in the range of 620 nm and by hypsochromic
      shift from 620 to 606 nm (~14 nm) in UV-Vis spectrophotometer. Analysis of
      variance was used for optimization of the slope of the calibration curve by using
      the assay mixture containing 0.017% (w/v) alcian blue in 2% (v/v) acetic acid at
      pH 3.0. The high-throughput colorimetric assay method on microtiter plates was
      used for quantification of beta-d-glucans in the range of 0-0.8 MUg, with a slope
      of 44.15 * 10(-2) and a limit of detection of 0.017 MUg/well. Recovery
      experiments were carried out by using a sample of Hericium erinaceus, which
      exhibited a recovery of 95.8% for beta-1,3-d-glucan. The present assay method
      exhibited a 10-fold higher sensitivity and a 59-fold lower limit of detection
      compared with the published method with congo red. beta-d-glucans of several
      mushrooms strains were isolated from fruiting bodies and mycelia, and they were
      quantified by this assay method. This assay method is fast, specific, simple, and
      it can be used to quantify beta-d-glucans from other biological sources.

PMID- 26317583
TI  - Implementing endoscopic optical diagnosis into practice: a green light at the
      horizon.

PMID- 26317584
TI  - Will the robot take over endoscopy?

PMID- 26317585
TI  - Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy
      (ESGE) Guideline.
AB  - This Guideline is an official statement of the European Society of
      Gastrointestinal Endoscopy (ESGE). The Grading of Recommendations Assessment,
      Development, and Evaluation (GRADE) system 1 2 was adopted to define the strength
      of recommendations and the quality of evidence. MAIN RECOMMENDATIONS: 1 ESGE
      recommends endoscopic en bloc resection for superficial esophageal squamous cell
      cancers (SCCs), excluding those with obvious submucosal involvement (strong
      recommendation, moderate quality evidence). Endoscopic mucosal resection (EMR)
      may be considered in such lesions when they are smaller than 10 mm if en bloc
      resection can be assured. However, ESGE recommends endoscopic submucosal
      dissection (ESD) as the first option, mainly to provide an en bloc resection with
      accurate pathology staging and to avoid missing important histological features
      (strong recommendation, moderate quality evidence). 2 ESGE recommends endoscopic
      resection with a curative intent for visible lesions in Barrett's esophagus
      (strong recommendation, moderate quality evidence). ESD has not been shown to be
      superior to EMR for excision of mucosal cancer, and for that reason EMR should be
      preferred. ESD may be considered in selected cases, such as lesions larger than
      15 mm, poorly lifting tumors, and lesions at risk for submucosal invasion (strong
      recommendation, moderate quality evidence). 3 ESGE recommends endoscopic
      resection for the treatment of gastric superficial neoplastic lesions that
      possess a very low risk of lymph node metastasis (strong recommendation, high
      quality evidence). EMR is an acceptable option for lesions smaller than 10 - 15
      mm with a very low probability of advanced histology (Paris 0-IIa). However, ESGE
      recommends ESD as treatment of choice for most gastric superficial neoplastic
      lesions (strong recommendation, moderate quality evidence). 4 ESGE states that
      the majority of colonic and rectal superficial lesions can be effectively removed
      in a curative way by standard polypectomy and/or by EMR (strong recommendation,
      moderate quality evidence). ESD can be considered for removal of colonic and
      rectal lesions with high suspicion of limited submucosal invasion that is based
      on two main criteria of depressed morphology and irregular or nongranular surface
      pattern, particularly if the lesions are larger than 20 mm; or ESD can be
      considered for colorectal lesions that otherwise cannot be optimally and
      radically removed by snare-based techniques (strong recommendation, moderate
      quality evidence).

PMID- 26317586
TI  - Anesthesia for complex endoscopy: a made-to-measure suit.

PMID- 26317587
TI  - Reply to Sbaraglia et al.

PMID- 26317590
TI  - [Not Available].

PMID- 26317591
TI  - Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of
      Insomnia.
AB  - Since its discovery in 1998, the orexin system, composed of two G-protein coupled
      receptors, orexins 1 and 2, and two neuropeptide agonists, orexins A and B, has
      captured the attention of the scientific community as a potential therapeutic
      target for the treatment of obesity, anxiety, and sleep/wake disorders. Genetic
      evidence in rodents, dogs, and humans was revealed between 1999 and 2000,
      demonstrating a causal link between dysfunction or deletion of the orexin system
      and narcolepsy, a disorder characterized by hypersomnolence during normal
      wakefulness. These findings encouraged efforts to discover agonists to treat
      narcolepsy and, alternatively, antagonists to treat insomnia. This perspective
      will focus on the discovery and development of structurally diverse orexin
      antagonists suitable for preclinical pharmacology studies and human clinical
      trials. The work described herein culminated in the 2014 FDA approval of
      suvorexant as a first-in-class dual orexin receptor antagonist for the treatment
      of insomnia.

PMID- 26317592
TI  - Do Brain Networks Evolve by Maximizing Their Information Flow Capacity?
AB  - We propose a working hypothesis supported by numerical simulations that brain
      networks evolve based on the principle of the maximization of their internal
      information flow capacity. We find that synchronous behavior and capacity of
      information flow of the evolved networks reproduce well the same behaviors
      observed in the brain dynamical networks of Caenorhabditis elegans and humans,
      networks of Hindmarsh-Rose neurons with graphs given by these brain networks. We
      make a strong case to verify our hypothesis by showing that the neural networks
      with the closest graph distance to the brain networks of Caenorhabditis elegans
      and humans are the Hindmarsh-Rose neural networks evolved with coupling strengths
      that maximize information flow capacity. Surprisingly, we find that global neural
      synchronization levels decrease during brain evolution, reflecting on an
      underlying global no Hebbian-like evolution process, which is driven by no
      Hebbian-like learning behaviors for some of the clusters during evolution, and
      Hebbian-like learning rules for clusters where neurons increase their
      synchronization. 

PMID- 26317593
TI  - A Comparative Insight into Amprenavir Resistance of Mutations V32I, G48V, I50V,
      I54V, and I84V in HIV-1 Protease Based on Thermodynamic Integration and MM-PBSA
      Methods.
AB  - Drug resistance of mutations V32I, G48V, I50V, I54V, and I84V in HIV-1 protease
      (PR) was found in clinical treatment of HIV patients with the drug amprenavir
      (APV). In order to elucidate the molecular mechanism of drug resistance
      associated with these mutations, the thermodynamic integration (TI) and molecular
      mechanics Poisson-Boltzmann surface area (MM-PBSA) methods were applied to
      calculate binding free energies of APV to wild-type PR and these mutated PRs. The
      relative binding free energy differences from the TI calculations reveal that the
      decrease in van der Waals interactions of APV with mutated PRs relative to the
      wild-type PR mainly drives the drug resistance. This result is in good agreement
      with the previous experimental results and is also consistent with the results
      from MM-PBSA calculations. Analyses based on molecular dynamics trajectories show
      that these mutations can adjust the shape and conformation of the binding pocket,
      which provides main contributions to the decrease in the van der Waals
      interactions of APV with mutated PRs. The present study could provide important
      guidance for the design of new potent inhibitors that could alleviate drug
      resistance of PR due to mutations. 

PMID- 26317594
TI  - Testing yawning hypotheses in wild populations of two strepsirrhine species:
      Propithecus verreauxi and Lemur catta.
AB  - Yawning, although easily recognized, is difficult to explain. Traditional
      explanations stressed physiological mechanisms, but more recently, behavioral
      processes have received increasing attention. This is the first study to test a
      range of hypotheses on yawning in wild primate populations. We studied two
      sympatric strepsirrhine species, Lemur catta, and Propithecus verreauxi, of the
      Ankoba forest (24.99 degrees S, 46.29 degrees E, Berenty reserve) in southern
      Madagascar. Sexual dimorphism is lacking in both species. However, their
      differences in ecological and behavioral characteristics facilitate comparative
      tests of hypotheses on yawning. Our results show that within each species males
      and females yawned with similar frequencies supporting the Dimorphism Hypothesis,
      which predicts that low sexual dimorphism leads to little inter-sexual
      differences in yawning. In support of the State Changing Hypothesis yawning
      frequencies was linked to the sleep-wake cycle and punctuated transitions from
      one behavior to another. Accordingly, yawning frequencies were significantly
      higher in L. catta than in P. verreauxi, because L. catta has a higher basal
      level of activity and consequently a higher number of behavioral transitions. In
      agreement with the Anxiety Hypothesis, yawning increased significantly in the 10
      min following predatory attacks or aggression. Our findings provide the first
      empirical evidence of a direct connection between anxiety and yawning in lemurs.
      Our results show that yawning in these two strepsirrhines occurs in different
      contexts, but more research will be necessary to determine if yawns are a single,
      unitary behavior.

PMID- 26317595
TI  - Central Obesity and Advanced Liver Stiffness in Hepatitis B: Result from Golestan
      Hepatitis B Cohort Study.
AB  - BACKGROUND: Chronic infection with the hepatitis B virus and obesity may both
      contribute synergistically to liver disease, although relatively few studies have
      investigated this hypothesis. Therefore, in this study, we evaluated the
      relationship between central obesity and the liver stiffness in the Golestan
      Hepatitis B cohort study (GHBCS). METHODS: Our study included 304 chronic
      hepatitis B (CHB) patients enrolled from GHBCS. Liver stiffness measurement (LSM)
      and laboratory tests were performed after a follow-up of 4 years (2012). The
      hepatitis B viral load was measured at the baseline and follow-up using the real
      time PCR method. Waist circumference >= 102 cm in men and >= 89 cm in women
      (central obesity) was considered to be abnormal. Advanced liver stiffness (ALS)
      was defined as LSM >= 8 KPa. Statistical analysis was performed using SPSS-V17.
      Logistic regression was used to test predictors of advanced liver stiffness (LSM
      >= 8 KPa). Linear regression was used to test the predictive value of variables
      in ALT (as a continuous variable). P-value of less than 0.05 was considered
      statistically significant. RESULTS: Among these CHB patients, 19 (7.4%) cases
      with a mean (+/-SD) age of 49.5 (+/-6.3) developed ALS after 4 years of follow
      up. Multivariate analysis showed a significant predictive role of central obesity
      and viral load in ALS. CONCLUSIONS: Central obesity is related to the liver
      stiffness in chronic hepatitis B patients.

PMID- 26317596
TI  - Opium as a Risk Factor for Bladder Cancer: A Population-based Case-control Study
      in Iran.
AB  - BACKGROUND: Bladder cancer (BC) is the most common genitourinary system
      malignancy in humans. Consumption of opium and its derivatives, maybe a risk
      factor possibly in Iran. The aim of this study was to investigate the
      relationship between consumption of opium and its derivatives and the incidence
      of BC. METHODS: In an individually matched case-control study in Shiraz (located
      in the south of Iran), 198 patients with BC and 396 healthy individuals (matched
      in age, sex and residence (urban/rural)) were investigated. Data about
      consumption of opium and its derivatives, tobacco, alcohol and diet were
      collected using a structured valid and reliable questionnaire. Crude and adjusted
      odds ratios (ORs) were computed using conditional logistic regression models.
      RESULTS: Opium consumption was associated with an increased risk of BC with an
      adjusted OR = 3.9 (95% CI: 1.2 - 12.0). Moreover, a considerable dose-response
      relationship was observed between the opium consumption and its derivatives and
      the incidence of BC; comparing to no users, the odds ratios of low and high
      consumptions were 3.3 (95% CI: 0.5 - 23.1) and 4.9 (95% CI: 1.1 - 21.9)
      respectively. CONCLUSION: Opium consumption can be a potential strong risk factor
      for BC in Iran.

PMID- 26317597
TI  - Insulin Resistance in Patients with Benign Thyroid Nodules.
AB  - OBJECTIVE: Recently, it has been questioned whether insulin resistance is
      associated with thyroid nodules. The aim of this study was to examine insulin
      resistance prevalence in a case-control study of patients with benign thyroid
      nodules in an iodine-sufficient area. METHODS: This was a single-center, case
      control study on euthyroid patients with benign nodular diseases. Thirty newly
      diagnosed patients with benign thyroid nodules according to fine needle
      aspiration cytology were investigated for insulin resistance. As a control group,
      30 euthyroid control subjects with normal thyroid sonography without nodule were
      recruited from the general population. The participants were matched in pairs by
      age, gender, and body mass index. The diagnosis of insulin resistance was made
      when the homeostasis model assessment of insulin resistance (HOMA-IR) index was
      more than 2.5. RESULTS: The mean of HOMA-IR value was significantly higher in
      patients compared to controls (1.32 +/- 0.65 vs. 0.76 +/- 0.36, P-value < 0.001).
      Insulin resistance was seen in two subjects with thyroid nodules (6.7%), but none
      in the control group. There was a positive significant correlation between HOMA
      IR and thyroid nodule size (r-value: +0.38, P < 0.03). CONCLUSION: Patients with
      thyroid nodules have higher HOMA-IR value. There is an association between
      insulin resistance and benign thyroid nodules. More investigations are required
      to define the role of this factor in thyroid nodule formation.

PMID- 26317598
TI  - Treatment of Primary Central Nervous System Lymphoma with High-dose Methotrexate
      and Radiotherapy in HIV-negative Patients.
AB  - BACKGROUND: We assessed the outcome of high-dose methotrexate (HD-MTX)
      chemotherapy with or without radiotherapy (RT) in primary central nervous system
      lymphoma (PCNSL) patients. METHODS: Fifty-one HIV-negative patients with an
      average age of 50.3 years were treated with chemotherapy regimen included 2500
      mg/m(2) MTX with Leucovorin rescue and 1.4 mg/m(2) vincristine (day two), which
      was administered every other week for 6 weeks. Only the patients who were younger
      than 60 years received RT. All patients received two cycles of 3000 mg/m(2)
      cytarabine at the end of the treatment for two successive days. RESULTS: Diffuse
      large B-cell lymphoma was the most common histologic subtype (90.2%), and twenty
      six (51.0%)patients had multiple brain lesions. The median survival of patients
      who were younger than 60 years was 37 months. For patients who were older than 60
      years, the median survival was 20 months. The median survival of men and women
      were 30 and 34 months, respectively. There was no significant difference in
      survival of patients in terms of age and sex. Overall, sixteen patients (31%) out
      of fifty-one patients died, five of them were older than 60 years and eleven were
      younger than 60 years. Twenty-five (49%) of all patients experienced relapse, and
      10 (40%) of them died after rechemotherapy. CONCLUSIONS: The base of our
      chemotherapy regimen was HD-MTX as the regular doses of MTX cannot penetrate the
      blood brain barrier (BBB). Our results indicated that the combination of HD-MTX
      with RT may not influence the outcome of PCNSL; thus, RT cannot be the first line
      therapy.

PMID- 26317599
TI  - General Practitioners' Knowledge and Clinical Practice in Management of People
      with Type 2 Diabetes in Iran; The Impact of Continuous Medical Education
      Programs.
AB  - BACKGROUND: To obtain information related to the knowledge and clinical practice
      of general practitioners (GPs) in management of people with type 2 diabetes, and
      to explore the impact of formal continuous medical education (CME) programs.
      METHODS: A total of 1104 GPs participated in a cross sectional survey related to
      diabetes management considering ADA/EASD consensus 2011 focused on demographic
      and background characteristics, diabetes related knowledge, and patient care.
      Fisher's Exact and Chi-square tests were used in the analysis of contingency
      tables. RESULTS: The majority of the participants (83.9%) worked in large cities
      and 39.8% had taken part in CME programs in diabetes management. Overall, 52% of
      the GPs knew the treatment goal for HbA1c. The rate was slightly higher for those
      taken part in CME (P = 0.003). Considering patient care, slightly more than half
      of the participants answered correctly to the questions on duration and
      distribution of physical activity, with no difference by taking part in CME
      programs. On average, 41.5% of the physicians selected metformin as the first
      OGLD for treatment of type 2 diabetes, and only 27.9% stated that they add basal
      insulin to OGLD if treatment failed. CONCLUSION: The results of this study
      provide the evidence that the knowledge and clinical practice of Iranian GPs in
      management of type 2 diabetes were not satisfactory. Furthermore, traditional CME
      programs in diabetes management were not effective in changing the GPs' clinical
      practice. Consequently, designing and implementing more effective strategies are
      necessary for improving patient health related outcomes.

PMID- 26317600
TI  - Iron Oxide Nanoparticles Reduced Retinoic Acid Induced-neuronal Differentiation
      of Mouse Embryonic Stem Cells By ROS Generation.
AB  - BACKGROUND: In recent years the increasing use of nanoparticles has led
      researchers to study their effects on biological systems. The most important
      effects of nanoparticles on cells are their ability to induce or suppress
      production of reactive oxygen species (ROS). Changes in reactive oxygen species
      play an important role in various developmental processes, including
      proliferation and differentiation in several diseases such as Parkinson. The aim
      of this study was to investigate the effect of iron oxide nanoparticle with
      dimensions of less than 20 nanometers on the viability and neuronal
      differentiation of mouse embryonic stem cell (Royan B1). METHODS: To assess the
      effects of Fe2O3 nanoparticles on neuronal differentiation of Royan B1 cells,
      embryoid bodies were divided into eight groups receiving different amounts of
      nanoparticle (10, 20, 30 MUg/mL) for 12 hours, retinoic acid (1 MUM), and both.
      Differentiation was examined under phase contrast microscope and using
      immunocytochemistry. RESULTS: Data analysis showed that cell death was increased
      by a time and concentration manner and there was a direct relevance between iron
      oxide amount and H2O2 level in cells. Statistical analysis of embryoid bodies
      showed that neural differentiation of mouse embryonic stem cells in groups that
      received nanoparticles were significantly lower than other groups and their
      viability were considerably reduced. CONCLUSION: According to the findings of
      this study it can be concluded that iron oxide nanoparticles reduce retinoic acid
      neuronal differentiation in mouse embryonic stem cells and it seems that the main
      mechanism involved  in the reduction of viability and neural differentiation was
      enhanced levels of ROS within the cells.

PMID- 26317601
TI  - The Modulatory Role of Dopamine in Anxiety-like Behavior.
AB  - Anxiety is an unpleasant physiological state in which an overreaction to a
      situation occurs. It has been suggested that different brain regions are involved
      in the modulation and expression of anxiety, including the amygdala, hippocampus,
      and frontal cortex. Dysfunction of neurotransmitters and their receptors can lead
      to many mood disorders like anxiety. There are evidences that dopamine plays an
      important role in anxiety modulation in different parts of the brain. Some
      evidence has shown that the mesolimbic, mesocortical and nigrostriatal
      dopaminergic system are involved in anxiety. Both dopamine D1 and D2 receptor
      mechanisms are important in mediating anxiety. The activity of dopaminergic
      system is modulated by several neurotransmitters, including glutamatergic neurons
      from the medial prefrontal cortex (mPFC), GABAergic fibers from the nucleus
      accumbens (NAc) as well as the ventral pallidum and cholinergic fibers from the
      pedunculopontine nucleus and the laterodorsal tegmental nucleus. Thus, changes in
      the glutamatergic, and GABAergic, as well as mediated transmission in the
      mesolimbic, mesocortical and nigrostriatal dopaminergic system may influence
      anxiety-like behavior. 

PMID- 26317602
TI  - Extraintestinal Involvement of Rotavirus Infection in Children.
AB  - Rotaviruses (RVs), a member of Reoviridae family, are a major cause of severe
      diarrhea in children < 5 years of age worldwide, infecting mainly the
      gastrointestinal tract although recent findings have shown extraintestinal spread
      of RV infections. The RV is known to cause systemic infection in children with
      acute gastroenteritis (AGE). The systemic RV infection may lead to the virus
      reaching extraintestinal organs, therefore developing clinical symptoms. RV RNA,
      antigen, and infectious particles have been found in serum, cerebrospinal fluid
      (CSF) and extraintestinal tissues in children with AGE. According to previous
      studies on molecular genotyping of RV, no specific association has been yet found
      between antigenemia and RV G genotype. However, nucleotide changes and genotype
      discordance in RVs have been detected in paired stool and serum samples. In
      children, who show the evidence of antigenemia, RV genome is detectable in
      extraintestinal organs. Although, clinical significance of the laboratory
      findings remains to be determined. 

PMID- 26317603
TI  - Bilateral Cystoid Macular Edema Secondary to Paclitaxel Treatment.
AB  - Cystoid macular edema is rarely observed secondary to paclitaxel treatment. A 55
      year-old female patient was applied five cures of paclitaxel and carboplatin
      chemotherapy after being diagnosed with metastatic ovarian cancer. The patient
      had a normal bilateral vision prior to the chemotherapy treatments. After the
      fifth cure, the patient complained of bilateral vision loss, which was more
      severe in the left eye. Ophthalmologic examination revealed that right eye vision
      was 4/10 blurred without glasses and 7/10 blurred with glasses, left eye vision
      was 1/10 blurred without glasses and 4/10 blurred with glasses. Pathology was not
      detected during the biomicroscopic examination. Fundus examination of the patient
      revealed pigment epithelium irregularity, which was found to be less in the right
      eye, and it was found a decrease in foveal cavity. For fundus examination, the
      patient underwent fundus fluorescein angiography (FFA) and optical coherence
      tomography (OCT). FFA revealed fluorescein leakage and cystoid appearance
      particularly more apparent in the left eye. Thickening in the macula and cystoid
      space was observed particularly more in the left eye in the OCT measurement. In
      conclusion, we presented our case as a rarely observed cystoid macular edema
      secondary to paclitaxel treatment. 

PMID- 26317604
TI  - Intraparenchimal Leiomyoma of the Breast.
AB  - The most common location of the leiomyoma is uterus, small bowel and the
      esophagus, however they can occur in any organ. Intraparenchimal leiomyomas of
      the breast are very rare and only 30 cases were reported in the literature. These
      histologically benign tumors, may mimic malignancies and therefore may present a
      diagnostic challenge. Here, we present two new cases. The first case was a 50
      year-old woman presented with a 4 cm firm mass in her right breast with discrete
      localized skin thickening/retraction. The second case was a 35-year-old woman
      presented with a painless palpable lump in the lower outer quadrant of her right
      breast. Physical examination, mammography and ultrasound as well as surgical
      excision were performed in both cases. According to histologic examination and
      immunohistochemical analysis, a diagnosis of smooth muscle tumor of the breast
      was made. These tumors clinically and radiologically mimic other breast lesions. 
      Neither imaging studies nor palpation allow distinction between benign and
      malignant tumors. 

PMID- 26317605
TI  - Rhombencephalitis by Listeria Monocytogens in Two Diabetic Patients.
AB  - Brainstem involvement is a characteristic feature and accounts for the high
      mortality associated with listeriosis especially in immunosuppressed patients. We
      report two cases of rhombencephalitis infection by Listeria monocytogenes in a 65
      and 63-year-old men with diabetes. They were referred to a neurologist due to
      fever and drowsiness after 3 weeks. The 65-year-old man had vertigo, diplopia,
      ataxia, bidirectional nystagmus and the 63-year-old man complained of perioral
      numbness, dysphagia and dysartheria. Treatment with ampicillin (12 g/day) was
      started empirically and modified when the culture results were available. The CSF
      cultures were positive to Listeria monocytogenes and brain MRI findings were
      suggestive of rhomboencephalitis. Despite delays in treatment, they had a
      complete clinical recovery with resolution of MRI abnormalities. In contrast to
      our results, in most reports, a bi-phasic illness has ?been described and late
      treatment was associated with unfavorable courses or long lasting sequelae. 

PMID- 26317606
TI  - A Rare Foreign Material in the Bladder: Piece of Pencil.
AB  - Cases with foreign bodies in the bladder are rarely seen. According to
      literature, it has been reported that foreign bodies were removed from the
      bladder. The etiology of these cases are iatrogenic causes, migration from
      adjacent organs, tissues and self-insertion. In this case report, we presented a
      22-year-old female who was admitted to the emergency room with vaginal bleeding,
      and groin pain. The foreign body was removed from the urinary bladder. 

PMID- 26317607
TI  - The Discourse of Medicine in the Cahar Maqala (Four Discourses) of Nezami Aruzi
      of Samarghand.
AB  - Nezami Aruzi prepared Cahar Maqala (Four Discourses) as a guide and admonishment
      for the rulers and kings. The fourth discourse of Cahar Maqala with 12 anecdotes
      is devoted to the science of medicine and the characteristics of the physicians.
      The discourse presents the name of the eminent scientists, physicians, as well as
      Farsi and Arabic medical books that had professional acceptance in the medieval
      in Persia. The author has described how medicine was studied in the medieval in
      Persia and has presented notes on the physiology of the nervous system, pulse,
      uroscopy, fever, spiritual affairs and medical ethics. The current essay is a
      brief review of the medical subjects in Cahar Maqala. 

PMID- 26317608
TI  - Affective Balance, Team Prosocial Efficacy and Team Trust: A Multilevel Analysis
      of Prosocial Behavior in Small Groups.
AB  - Little research has focused on how individual- and team-level characteristics
      jointly influence, via interaction, how prosocially individuals behave in teams
      and few studies have considered the potential influence of team context on
      prosocial behavior. Using a multilevel perspective, we examined the relationships
      between individual (affective balance) and group (team prosocial efficacy and
      team trust) level variables and prosocial behavior towards team members. The
      participants were 123 students nested in 45 small teams. A series of multilevel
      random models was estimated using hierarchical linear and nonlinear modeling.
      Individuals were more likely to behave prosocially towards in-group members when
      they were feeling good. Furthermore, the relationship between positive affective
      balance and prosocial behavior was stronger in teams with higher team prosocial
      efficacy levels as well as in teams with higher team trust levels. Finally, the
      relevance of team trust had a stronger influence on behavior than team prosocial
      efficacy. 

PMID- 26317610
TI  - Imaging of prompt gamma rays emitted during delivery of clinical proton beams
      with a Compton camera: feasibility studies for range verification.
AB  - The purpose of this paper is to evaluate the ability of a prototype Compton
      camera (CC) to measure prompt gamma rays (PG) emitted during delivery of clinical
      proton pencil beams for prompt gamma imaging (PGI) as a means of providing in
      vivo verification of the delivered proton radiotherapy beams. A water phantom was
      irradiated with clinical 114 MeV and 150 MeV proton pencil beams. Up to 500 cGy
      of dose was delivered per irradiation using clinical beam currents. The prototype
      CC was placed 15 cm from the beam central axis and PGs from 0.2 MeV up to 6.5 MeV
      were measured during irradiation. From the measured data (2D) images of the PG
      emission were reconstructed. (1D) profiles were extracted from the PG images and
      compared to measured depth dose curves of the delivered proton pencil beams. The
      CC was able to measure PG emission during delivery of both 114 MeV and 150 MeV
      proton beams at clinical beam currents. 2D images of the PG emission were
      reconstructed for single 150 MeV proton pencil beams as well as for a 5   *   5
      cm mono-energetic layer of 114 MeV pencil beams. Shifts in the Bragg peak (BP)
      range were detectable on the 2D images. 1D profiles extracted from the PG images
      show that the distal falloff of the PG emission profile lined up well with the
      distal BP falloff. Shifts as small as 3 mm in the beam range could be detected
      from the 1D PG profiles with an accuracy of 1.5 mm or better. However, with the
      current CC prototype, a dose of 400 cGy was required to acquire adequate PG
      signal for 2D PG image reconstruction. It was possible to measure PG interactions
      with our prototype CC during delivery of proton pencil beams at clinical dose
      rates. Images of the PG emission could be reconstructed and shifts in the BP
      range were detectable. Therefore PGI with a CC for in vivo range verification
      during proton treatment delivery is feasible. However, improvements in the
      prototype CC detection efficiency and reconstruction algorithms are necessary to
      make it a clinically viable PGI system.

PMID- 26317611
TI  - One-Pot, Four-Step Organocatalytic Asymmetric Synthesis of Functionalized
      Nitrocyclopropanes.
AB  - The asymmetric synthesis of functionalized nitrocyclopropanes has been achieved
      by a one-pot, four-step method catalyzed by (S)-diphenylprolinol TMS ether, which
      joins two sequential domino reactions, namely a domino sulfa-Michael/aldol
      condensation of alpha,beta-unsaturated aldehydes with 1,4-dithiane-2,5-diol, and
      a domino Michael/alpha-alkylation reaction of the derived chiral
      dihydrothiophenes with bromonitromethane. The title compounds were obtained in 27
      45% yields, with high levels of diastereoselectivity (93:7 to 100:0 dr) and
      generally good enantioselectivities (up to 95:5 er). 

PMID- 26317609
TI  - Effects of Antenatal Maternal Depression and Anxiety on Children's Early
      Cognitive Development: A Prospective Cohort Study.
AB  - INTRODUCTION: Studies have shown that depression or anxiety occur in 10-20% of
      pregnant women. These disorders are often undertreated and may affect mothers and
      children's health. This study investigates the relation between antenatal
      maternal depression, anxiety and children's early cognitive development among
      1380 two-year-old children and 1227 three-year-old children. METHODS: In the
      French EDEN Mother-Child Cohort Study, language ability was assessed with the
      Communicative Development Inventory at 2 years of age and overall development
      with the Ages and Stages Questionnaire at 3 years of age. Multiple regressions
      and structural equation modeling were used to examine links between depression,
      anxiety during pregnancy and child cognitive development. RESULTS: We found
      strong significant associations between maternal antenatal anxiety and poorer
      children's cognitive development at 2 and 3 years. Antenatal maternal depression
      was not associated with child development, except when antenatal maternal anxiety
      was also present. Both postnatal maternal depression and parental stimulation
      appeared to play mediating roles in the relation between antenatal maternal
      anxiety and children's cognitive development. At 3 years, parental stimulation
      mediated 13.2% of the effect of antenatal maternal anxiety while postnatal
      maternal depression mediated 26.5%. DISCUSSION: The partial nature of these
      effects suggests that other mediators may play a role. Implications for theory
      and research on child development are discussed.

PMID- 26317612
TI  - From Rain Tanks to Catchments: Use of Low-Impact Development To Address
      Hydrologic Symptoms of the Urban Stream Syndrome.
AB  - Catchment urbanization perturbs the water and sediment budgets of streams,
      degrades stream health and function, and causes a constellation of flow, water
      quality, and ecological symptoms collectively known as the urban stream syndrome.
      Low-impact development (LID) technologies address the hydrologic symptoms of the
      urban stream syndrome by mimicking natural flow paths and restoring a natural
      water balance. Over annual time scales, the volumes of stormwater that should be
      infiltrated and harvested can be estimated from a catchment-scale water-balance
      given local climate conditions and preurban land cover. For all but the wettest
      regions of the world, a much larger volume of stormwater runoff should be
      harvested than infiltrated to maintain stream hydrology in a preurban state.
      Efforts to prevent or reverse hydrologic symptoms associated with the urban
      stream syndrome will therefore require: (1) selecting the right mix of LID
      technologies that provide regionally tailored ratios of stormwater harvesting and
      infiltration; (2) integrating these LID technologies into next-generation
      drainage systems; (3) maximizing potential cobenefits including water supply
      augmentation, flood protection, improved water quality, and urban amenities; and
      (4) long-term hydrologic monitoring to evaluate the efficacy of LID
      interventions.

PMID- 26317613
TI  - Serine Phosphorylation of HIV-1 Vpu and Its Binding to Tetherin Regulates
      Interaction with Clathrin Adaptors.
AB  - HIV-1 Vpu prevents incorporation of tetherin (BST2/ CD317) into budding virions
      and targets it for ESCRT-dependent endosomal degradation via a clathrin-dependent
      process. This requires a variant acidic dileucine-sorting motif (ExxxLV) in Vpu.
      Structural studies demonstrate that recombinant Vpu/tetherin fusions can form a
      ternary complex with the clathrin adaptor AP-1. However, open questions still
      exist about Vpu's mechanism of action. Particularly, whether endosomal
      degradation and the recruitment of the E3 ubiquitin ligase SCFbetaTRCP1/2 to a
      conserved phosphorylated binding site, DSGNES, are required for antagonism. Re
      evaluation of the phenotype of Vpu phosphorylation mutants and naturally
      occurring allelic variants reveals that the requirement for the Vpu phosphoserine
      motif in tetherin antagonism is dissociable from SCFbetaTRCP1/2 and ESCRT
      dependent tetherin degradation. Vpu phospho-mutants phenocopy ExxxLV mutants, and
      can be rescued by direct clathrin interaction in the absence of SCFbetaTRCP1/2
      recruitment. Moreover, we demonstrate physical interaction between Vpu and AP-1
      or AP-2 in cells. This requires Vpu/tetherin transmembrane domain interactions as
      well as the ExxxLV motif. Importantly, it also requires the Vpu phosphoserine
      motif and adjacent acidic residues. Taken together these data explain the
      discordance between the role of SCFbetaTRCP1/2 and Vpu phosphorylation in
      tetherin antagonism, and indicate that phosphorylation of Vpu in Vpu/tetherin
      complexes regulates promiscuous recruitment of adaptors, implicating clathrin
      dependent sorting as an essential first step in tetherin antagonism. 

PMID- 26317614
TI  - Breast Cancer Anti-Estrogen Resistance 4 (BCAR4) Drives Proliferation of IPH-926
      lobular Carcinoma Cells.
AB  - BACKGROUND: Most breast cancers depend on estrogenic growth stimulation.
      Functional genetic screenings in in vitro cell models have identified genes,
      which override growth suppression induced by anti-estrogenic drugs like
      tamoxifen. Using that approach, we have previously identified Breast Cancer Anti
      Estrogen Resistance 4 (BCAR4) as a mediator of cell proliferation and tamoxifen
      resistance. Here, we show high level of expression and function of BCAR4 in human
      breast cancer. METHODS: BCAR4 mRNA expression was evaluated by (q)RT-PCR in a
      panel of human normal tissues, primary breast cancers and cell lines. A new
      antibody raised against C78-I97 of the putative BCAR4 protein and used for
      western blot and immunoprecipitation assays. Furthermore, siRNA-mediated gene
      silencing was implemented to study the function of BCAR4 and its downstream
      targets ERBB2/3. RESULTS: Except for placenta, all human normal tissues tested
      were BCAR4-negative. In primary breast cancers, BCAR4 expression was
      comparatively rare (10%), but associated with enhanced proliferation. Relative
      high BCAR4 mRNA expression was identified in IPH-926, a cell line derived from an
      endocrine-resistant lobular breast cancer. Moderate BCAR4 expression was evident
      in MDA-MB-134 and MDA-MB-453 breast cancer cells. BCAR4 protein was detected in
      breast cancer cells with ectopic (ZR-75-1-BCAR4) and endogenous (IPH-926, MDA-MB
      453) BCAR4 mRNA expression. Knockdown of BCAR4 inhibited cell proliferation. A
      similar effect was observed upon knockdown of ERBB2/3 and exposure to lapatinib,
      implying that BCAR4 acts in an ERBB2/3-dependent manner. CONCLUSION: BCAR4
      encodes a functional protein, which drives proliferation of endocrine-resistant
      breast cancer cells. Lapatinib, a clinically approved EGFR/ERBB2 inhibitor,
      counteracts BCAR4-driven tumor cell growth, a clinical relevant observation.

PMID- 26317615
TI  - Plasma HMGB-1 Levels in Subjects with Obesity and Type 2 Diabetes: A Cross
      Sectional Study in China.
AB  - OBJECT: To detect the levels of plasma High-Mobility Group Box-1(HMGB1) in
      Chinese subject with obesity and type 2 diabetes mellitus (T2DM), and to
      investigate the correlations between plasma HMGB1 concentration and parameters of
      body fat, insulin resistance (IR) metabolism and inflammation. METHODS: This
      study recruited 79 normal glucose tolerance (NGT) subjects and 76 newly diagnosed
      T2DM patients. NGT and T2DM groups were divided into normal weight (NW) and obese
      (OB)subgroups respectively. Anthropometric parameters such as height, weight,
      waist circumference, hip circumference and blood pressure were measured. Plasma
      concentrations of HMGB1, IL-6, fasting plasma glucose (FPG), 2 hours post
      challenge plasma glucose (2hPG), serum lipid, glycated hemoglobin (HbA1C) and
      fasting insulin (FINS) were examined. The homeostasis model assessment (HOMA) was
      performed to assess IR status. RESULTS: Plasma HMGB1 levels were higher in T2DM
      group than that in NGT group. The concentrations of serum HMGB1 were also higher
      in subjects with OB than those in subjects with NW both in NGT and T2DM groups.
      Plasma levels of HMGB1 were positively correlated with waist hip ratio (WHR),
      blood pressure, FPG, FINS, HOMA-IR, TG, IL-6 and negatively correlated with HOMA
      betaand high-density lipoprotein-cholesterol (HDL-c) independent of age, gender
      and BMI. Plasma levels of HMGB1 were significantly correlated with diabetes in
      fully adjusted models. CONCLUSION: Plasma HMGB1 levels were increased in Chinese
      subjects with pure T2DM, which might be caused by IR. Serum HMGB1 participated in
      the pathological process of obesity and T2DM via its proinflammatory effect.

PMID- 26317616
TI  - Overexpression of ZmIRT1 and ZmZIP3 Enhances Iron and Zinc Accumulation in
      Transgenic Arabidopsis.
AB  - Iron and zinc are important micronutrients for both the growth and nutrient
      availability of crop plants, and their absorption is tightly controlled by a
      metal uptake system. Zinc-regulated transporters, iron-regulated transporter-like
      proteins (ZIP), is considered an essential metal transporter for the acquisition
      of Fe and Zn in graminaceous plants. Several ZIPs have been identified in maize,
      although their physiological function remains unclear. In this report, ZmIRT1 was
      shown to be specifically expressed in silk and embryo, whereas ZmZIP3 was a leaf
      specific gene. Both ZmIRT1 and ZmZIP3 were shown to be localized to the plasma
      membrane and endoplasmic reticulum. In addition, transgenic Arabidopsis plants
      overexpressing ZmIRT1 or ZmZIP3 were generated, and the metal contents in various
      tissues of transgenic and wild-type plants were examined based on ICP-OES and
      Zinpyr-1 staining. The Fe and Zn concentration increased in roots and seeds of
      ZmIRT1-overexpressing plants, while the Fe content in shoots decreased.
      Overexpressing ZmZIP3 enhanced Zn accumulation in the roots of transgenic plants,
      while that in shoots was repressed. In addition, the transgenic plants showed
      altered tolerance to various Fe and Zn conditions compared with wild-type plants.
      Furthermore, the genes associated with metal uptake were stimulated in ZmIRT1
      transgenic plants, while those involved in intra- and inter- cellular
      translocation were suppressed. In conclusion, ZmIRT1 and ZmZIP3 are functional
      metal transporters with different ion selectivities. Ectopic overexpression of
      ZmIRT1 may stimulate endogenous Fe uptake mechanisms, which may facilitate metal
      uptake and homeostasis. Our results increase our understanding of the functions
      of ZIP family transporters in maize. 

PMID- 26317617
TI  - Fate and Phytotoxicity of CeO2 Nanoparticles on Lettuce Cultured in the Potting
      Soil Environment.
AB  - Cerium oxide nanoparticles (CeO2 NPs) have been shown to have significant
      interactions in plants. Previous study reported the specific-species
      phytotoxicity of CeO2 NPs by lettuce (Lactuca sativa), but their physiological
      impacts and vivo biotransformation are not yet well understood, especially in
      relative realistic environment. Butterhead lettuce were germinated and grown in
      potting soil for 30 days cultivation with treatments of 0, 50, 100, 1000 mg CeO2
      NPs per kg soil. Results showed that lettuce in 100 mg.kg-1 treated groups grew
      significantly faster than others, but significantly increased nitrate content.
      The lower concentrations treatment had no impact on plant growth, compared with
      the control. However, the higher concentration treatment significantly deterred
      plant growth and biomass production. The stress response of lettuce plants, such
      as Superoxide dismutase (SOD), Peroxidase (POD), Malondialdehyde(MDA) activity
      was disrupted by 1000 mg.kg-1 CeO2 NPs treatment. In addition, the presence of Ce
      (III) in the roots of butterhead lettuce explained the reason of CeO2 NPs
      phytotoxicity. These findings demonstrate CeO2 NPs modification of nutritional
      quality, antioxidant defense system, the possible transfer into the food chain
      and biotransformation in vivo. 

PMID- 26317618
TI  - High Platelet Reactivity in Patients with Acute Coronary Syndromes Undergoing
      Percutaneous Coronary Intervention: Randomised Controlled Trial Comparing
      Prasugrel and Clopidogrel.
AB  - BACKGROUND: Prasugrel is more effective than clopidogrel in reducing platelet
      aggregation in acute coronary syndromes. Data available on prasugrel reloading in
      clopidogrel treated patients with high residual platelet reactivity (HRPR) i.e.
      poor responders, is limited. OBJECTIVES: To determine the effects of prasugrel
      loading on platelet function in patients on clopidogrel and high platelet
      reactivity undergoing percutaneous coronary intervention for acute coronary
      syndrome (ACS). PATIENTS: Patients with ACS on clopidogrel who were scheduled for
      PCI found to have a platelet reactivity >=40 AUC with the Multiplate Analyzer,
      i.e. "poor responders" were randomised to prasugrel (60 mg loading and 10 mg
      maintenance dose) or clopidogrel (600 mg reloading and 150 mg maintenance dose).
      The primary outcome measure was proportion of patients with platelet reactivity
      <40 AUC 4 hours after loading with study medication, and also at one hour
      (secondary outcome). 44 patients were enrolled and the study was terminated early
      as clopidogrel use decreased sharply due to introduction of newer P2Y12
      inhibitors. RESULTS: At 4 hours after study medication 100% of patients treated
      with prasugrel compared to 91% of those treated with clopidogrel had platelet
      reactivity <40 AUC (p = 0.49), while at 1 hour the proportions were 95% and 64%
      respectively (p = 0.02). Mean platelet reactivity at 4 and 1 hours after study
      medication in prasugrel and clopidogrel groups respectively were 12 versus 22 (p
      = 0.005) and 19 versus 34 (p = 0.01) respectively. CONCLUSIONS: Routine platelet
      function testing identifies patients with high residual platelet reactivity
      ("poor responders") on clopidogrel. A strategy of prasugrel rather than
      clopidogrel reloading results in earlier and more sustained suppression of
      platelet reactivity. Future trials need to identify if this translates into
      clinical benefit. TRIAL REGISTRATION: ClinicalTrials.gov NCT01339026.

PMID- 26317619
TI  - FMiR: A Curated Resource of Mitochondrial DNA Information for Fish.
AB  - Mitochondrial genome sequences have been widely used for evolutionary and
      phylogenetic studies. Among vertebrates, fish are an important, diverse group,
      and their mitogenome sequences are growing rapidly in public repositories. To
      facilitate mitochondrial genome analysis and to explore the valuable genetic
      information, we developed the Fish Mitogenome Resource (FMiR) database to provide
      a workbench for mitogenome annotation, species identification and microsatellite
      marker mining. The microsatellites are also known as simple sequence repeats
      (SSRs) and used as molecular markers in studies on population genetics, gene
      duplication and marker assisted selection. Here, easy-to-use tools have been
      implemented for mining SSRs and for designing primers to identify species/habitat
      specific markers. In addition, FMiR can analyze complete or partial mitochondrial
      genome sequence to identify species and to deduce relational distances among
      sequences across species. The database presently contains curated mitochondrial
      genomes from 1302 fish species belonging to 297 families and 47 orders reported
      from saltwater and freshwater ecosystems. In addition, the database covers
      information on fish species such as conservation status, ecosystem, family,
      distribution and occurrence downloaded from the FishBase and IUCN Red List
      databases. Those fish information have been used to browse mitogenome information
      for the species belonging to a particular category. The database is scalable in
      terms of content and inclusion of other analytical modules. The FMiR is running
      under Linux operating platform on high performance server accessible at URL
      http://mail.nbfgr.res.in/fmir. 

PMID- 26317620
TI  - Hepatitis E Virus in Cambodia: Prevalence among the General Population and
      Complete Genome Sequence of Genotype 4.
AB  - Hepatitis E virus (HEV) is a growing public health problem in many countries. In
      this study, we investigated HEV seroprevalence among the general population in
      the Siem Reap province, Cambodia, and performed HEV genetic analysis with the aim
      to develop an HEV prevention strategy. This seroepidemiological cross-sectional
      study conducted from 2010 to 2014 included 868 participants from four different
      locations in Siem Reap province, Cambodia. They answered questionnaires and
      provided blood samples for the analysis of hepatitis virus infections. Among the
      participants (360 men and 508 women; age range, 7-90 years), the prevalence of
      anti-HEV IgG was 18.4% (95% confidence interval: 15.9-21.0); HEV RNA was detected
      in two participants (0.23%) and was classified as genotype 3 and 4. Full-length
      genome of the genotype 4 isolate, CVS-Sie10, was sequenced; it contained 7,222
      nucleotides and three ORFs and demonstrated high sequence identity with the swine
      China isolates swGX40 (95.57%), SS19 (94.37%), and swDQ (91.94%). Multivariate
      logistic regression analysis revealed that men, elderly people, and house workers
      were risk groups significantly associated with the positivity for anti-HEV IgG.
      This is the first report on the detection of HEV genotype 4 in humans in Cambodia
      and on the complete genome sequence of HEV genotype 4 from this country. Our
      study demonstrates that new HEV infection cases occur frequently among the
      general population in Cambodia, and effective preventive measures are required. 

PMID- 26317621
TI  - A Multicenter Retrospective Review of Prone Position Ventilation (PPV) in
      Treatment of Severe Human H7N9 Avian Flu.
AB  - BACKGROUND: Patients with H7N9 avian flu concurrent with severe acute respiratory
      distress syndrome (ARDS) usually have a poor clinical outcome. Prone position
      ventilation (PPV) has been shown to improve the prognosis of patients with severe
      ARDS. This study explored the effects of PPV on the respiratory and circulatory
      mechanics of H7N9-infected patients with severe ARDS. METHODS: Individuals
      admitted to four hospitals designated for H7N9 patients in Guangdong province
      were treated with PPV, and their clinical data were recorded before and after
      receiving PPV. RESULTS: Six of 20 critically ill patients in the ICU received
      PPV. After treatment with 35 PPV sessions, the oxygenation index (OI) values of
      the six patients when measured post-PPV and post-supine position ventilation
      (SPV) were significantly higher than those measured pre-PPV (P < 0.05).The six
      patients showed no significant differences in their values for respiratory rate
      (RR), peak inspiratory pressure (PIP), tidal volume (TV) or arterial partial
      pressure of carbon dioxide (PaCO2) when compared pre-PPV, post-PPV, and post-SPV.
      Additionally, there were no significant differences in the mean values for
      arterial pressure (MAP), cardiac index (CI), central venous pressure (CVP), heart
      rate (HR), lactic acid (LAC) levels or the doses of norepinephrine (NE)
      administered when compared pre-PPV, post-PPV, and post-SPV. CONCLUSION: PPV
      provided improved oxygenation that was sustained after returning to a supine
      position, and resulted in decreased carbon dioxide retention. PPV can thus serve
      as an alternative lung protective ventilation strategy for use in patients with
      H7N9 avian flu concurrent with severe ARDS.

PMID- 26317622
TI  - Wood Extractives Promote Cellulase Activity on Cellulosic Substrates.
AB  - Deposition of hydrophobic wood extractives and representative model compounds, on
      the surface of cellulose prior to enzymatic hydrolysis was found to either
      enhance or inhibit the action of cellulase enzymes. The effect of these compounds
      was correlated with their chemical structure, which may in part explain the
      differential effects observed between softwood and hardwood extractives.
      Specifically, the addition of sterol, enhanced enzymatic hydrolysis of
      microcrystalline cellulose by 54%, whereas the addition of a triglyceride could
      inhibit the hydrolysis by 49%. The effects of the different extractives' could be
      explained by considering their Hansen solubility parameters. The amphiphilic
      and/or hydrophobic character of model extractives was found to be the variable
      that affected the deposition of extractives on cellulose surfaces and the
      eventual adsorption of cellulolytic enzymes on it. The observed beneficial
      effects of extractives are likely related to a reduction in the irreversible
      binding of the enzymes on the cellulose surface. 

PMID- 26317623
TI  - The Use of Acceleration to Code for Animal Behaviours; A Case Study in Free
      Ranging Eurasian Beavers Castor fiber.
AB  - Recent technological innovations have led to the development of miniature,
      accelerometer-containing electronic loggers which can be attached to free-living
      animals. Accelerometers provide information on both body posture and dynamism
      which can be used as descriptors to define behaviour. We deployed tri-axial
      accelerometer loggers on 12 free-ranging Eurasian beavers Castor fiber in the
      county of Telemark, Norway, and on four captive beavers (two Eurasian beavers and
      two North American beavers C. canadensis) to corroborate acceleration signals
      with observed behaviours. By using random forests for classifying behavioural
      patterns of beavers from accelerometry data, we were able to distinguish seven
      behaviours; standing, walking, swimming, feeding, grooming, diving and sleeping.
      We show how to apply the use of acceleration to determine behaviour, and
      emphasise the ease with which this non-invasive method can be implemented.
      Furthermore, we discuss the strengths and weaknesses of this, and the
      implementation of accelerometry on animals, illustrating limitations, suggestions
      and solutions. Ultimately, this approach may also serve as a template
      facilitating studies on other animals with similar locomotor modes and deliver
      new insights into hitherto unknown aspects of behavioural ecology. 

PMID- 26317624
TI  - The Diversity and Geographical Structure of Orientia tsutsugamushi Strains from
      Scrub Typhus Patients in Laos.
AB  - Orientia tsutsugamushi is the causative agent of scrub typhus, a disease
      transmitted by Leptotrombidium mites which is responsible for a severe and under
      reported public health burden throughout Southeast Asia. Here we use multilocus
      sequence typing (MLST) to characterize 74 clinical isolates from three geographic
      locations in the Lao PDR (Laos), and compare them with isolates described from
      Udon Thani, northeast Thailand. The data confirm high levels of diversity and
      recombination within the natural O. tsutsugamushi population, and a rate of mixed
      infection of ~8%. We compared the relationships and geographical structuring of
      the strains and populations using allele based approaches (eBURST), phylogenetic
      approaches, and by calculating F-statistics (FST). These analyses all point
      towards low levels of population differentiation between isolates from Vientiane
      and Udon Thani, cities which straddle the Mekong River which defines the Lao/Thai
      border, but with a very distinct population in Salavan, southern Laos. These data
      highlight how land use, as well as the movement of hosts and vectors, may impact
      on the epidemiology of zoonotic infections. 

PMID- 26317625
TI  - Conformational Properties of Seven Toac-Labeled Angiotensin I Analogues Correlate
      with Their Muscle Contraction Activity and Their Ability to Act as ACE
      Substrates.
AB  - Conformational properties of the angiotensin II precursor, angiotensin I (AngI)
      and analogues containing the paramagnetic amino acid TOAC (2,2,6,6
      tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid) at positions 0, 1, 3, 5,
      8, 9, and 10, were examined by EPR, CD, and fluorescence. The conformational data
      were correlated to their activity in muscle contraction experiments and to their
      properties as substrates of the angiotensin I-converting enzyme (ACE). Biological
      activity studies indicated that TOAC0-AngI and TOAC1-AngI maintained partial
      potency in guinea pig ileum and rat uterus. Kinetic parameters revealed that only
      derivatives labeled closer to the N-terminus (positions 0, 1, 3, and 5) were
      hydrolyzed by ACE, indicating that peptides bearing the TOAC moiety far from the
      ACE cleavage site (Phe8-His9 peptide bond) were susceptible to hydrolysis, albeit
      less effectively than the parent compound. CD spectra indicated that AngI
      exhibited a flexible structure resulting from equilibrium between different
      conformers. While the conformation of N-terminally-labeled derivatives was
      similar to that of the native peptide, a greater propensity to acquire folded
      structures was observed for internally-labeled, as well as C-terminally labeled,
      analogues. These structures were stabilized in secondary structure-inducing
      agent, TFE. Different analogues gave rise to different beta-turns. EPR spectra in
      aqueous solution also distinguished between N-terminally, internally-, and C
      terminally labeled peptides, yielding narrower lines, indicative of greater
      mobility for the former. Interestingly, the spectra of peptides labeled at, or
      close, to the C-terminus, showed that the motion in this part of the peptides was
      intermediate between that of N-terminally and internally-labeled peptides, in
      agreement with the suggestion of turn formation provided by the CD spectra.
      Quenching of the Tyr4 fluorescence by the differently positioned TOAC residues
      corroborated the data obtained by the other spectroscopic techniques. Lastly, we
      demonstrated the feasibility of monitoring the progress of ACE-catalyzed
      hydrolysis of TOAC-labeled peptides by following time-dependent changes in their
      EPR spectra. 

PMID- 26317626
TI  - Microtubule-Mediated Inositol Lipid Signaling Plays Critical Roles in Regulation
      of Blebbing.
AB  - Cells migrate by extending pseudopods such as lamellipodia and blebs. Although
      the signals leading to lamellipodia extension have been extensively investigated,
      those for bleb extension remain unclear. Here, we investigated signals for
      blebbing in Dictyostelium cells using a newly developed assay to induce blebbing.
      When cells were cut into two pieces with a microneedle, the anucleate fragments
      vigorously extended blebs. This assay enabled us to induce blebbing reproducibly,
      and analyses of knockout mutants and specific inhibitors identified candidate
      molecules that regulate blebbing. Blebs were also induced in anucleate fragments
      of leukocytes, indicating that this assay is generally applicable to animal
      cells. After cutting, microtubules in the anucleate fragments promptly
      depolymerized, followed by the extension of blebs. Furthermore, when intact cells
      were treated with a microtubule inhibitor, they frequently extended blebs. The
      depolymerization of microtubules induced the delocalization of inositol lipid
      phosphatidylinositol 3,4,5-trisphosphate from the cell membrane. PI3 kinase-null
      cells frequently extended blebs, whereas PTEN-null cells extended fewer blebs.
      From these observations, we propose a model in which microtubules play a critical
      role in bleb regulation via inositol lipid metabolism. 

PMID- 26317627
TI  - Atrial Fibrillation and Colonic Neoplasia in African Americans.
AB  - BACKGROUND: Colorectal cancer (CRC) and atrial fibrillation/flutter (AF) share
      several risk factors including increasing age and obesity. However, the
      association between CRC and AF has not been thoroughly examined, especially in
      African Americans. In this study we aimed to assess the prevalence of AF and its
      risk factors in colorectal neoplasia in an African American. METHODS: We reviewed
      records of 527 African American patients diagnosed with CRC and 1008 patients
      diagnosed with benign colonic lesions at Howard University Hospital from January
      2000 to December 2012. A control group of 731 hospitalized patients without any
      cancer or colonic lesion were randomly selected from the same time and age range,
      excluding patients who had diagnosis of both CRC and/or adenoma. The presence or
      absence of AF was based upon ICD-9 code documentation. The prevalence of AF in
      these three groups was compared by multivariate logistic regression. RESULTS: The
      prevalence of AF was highest among CRC patients (10%) followed by adenoma
      patients (7.2%) then the control group (5.4%, P for trend = 0.002). In the three
      groups of participants, older age (P<0.008) and heart failure (P<0.001) were
      significantly associated with higher risk of AF. After adjusting for these risk
      factors, CRC (OR: 1.4(95%CI):0.9-2.2, P = 0.2) and adenoma (OR: 1.1(95%CI):0.7
      1.6, P = 0.7) were not significantly associated AF compared to control group.
      CONCLUSIONS: AF is highly prevalent among CRC patients; 1 in 10 patients had AF
      in our study. The predictors of AF in CRC was similar to that in adenoma and
      other patients after adjustment for potential confounders suggesting that the
      increased AF risk in CRC is explained by higher prevalence of AF risk factors.

PMID- 26317628
TI  - Anti-Inflammatory Effects of Lactobacillus Rahmnosus and Bifidobacterium Breve on
      Cigarette Smoke Activated Human Macrophages.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major global health
      problem with cigarette smoke (CS) as the main risk factor for its development.
      Airway inflammation in COPD involves the increased expression of inflammatory
      mediators such as CXCL-8 and IL-1beta which are important mediators for
      neutrophil recruitment. Macrophages are an important source of these mediators in
      COPD. Lactobacillus rhamnosus (L. rhamnosus) and Befidobacterium breve (B. breve)
      attenuate the development of 'allergic asthma' in animals but their effects in
      COPD are unknown. OBJECTIVE: To determine the anti-inflammatory effects of L.
      rhamnosus and B. breve on CS and Toll-like receptor (TLR) activation. DESIGN: We
      stimulated the human macrophage cell line THP-1 with CS extract in the presence
      and absence of L. rhamnosus and B. breve and measured the expression and release
      of inflammatory mediators by RT-qPCR and ELISA respectively. An activity assay
      and Western blotting were used to examine NF-kappaB activation. RESULTS: Both L.
      rhamnosus and B. breve were efficiently phagocytized by human macrophages. L.
      rhamnosus and B. breve significantly suppressed the ability of CS to induce the
      expression of IL-1beta, IL-6, IL-10, IL-23, TNFalpha, CXCL-8 and HMGB1 release
      (all p<0.05) in human THP-1 macrophages. Similar suppression of TLR4- and TLR9
      induced CXCL8 expression was also observed (p<0.05). The effect of L. rhamnosus
      and B. breve on inflammatory mediator release was associated with the suppression
      of CS-induced NF-kappaB activation (p<0.05). CONCLUSIONS: This data indicate that
      these probiotics may be useful anti-inflammatory agents in CS-associated disease
      such as COPD.

PMID- 26317629
TI  - The Effect of Preoperative Oral Carbohydrate or Oral Rehydration Solution on
      Postoperative Quality of Recovery: A Randomized, Controlled Clinical Trial.
AB  - BACKGROUND: Numerous studies have demonstrated the beneficial effects of
      preoperative administration of oral carbohydrate (CHO) or oral rehydration
      solution (ORS). However, the effects of preoperative CHO or ORS on postoperative
      quality of recovery after anesthesia remain unclear. Consequently, the purpose of
      the current study was to evaluate the effect of preoperative CHO or ORS on
      patient recovery, using the Quality of Recovery 40 questionnaire (QoR-40).
      METHODS: This prospective, randomized, controlled clinical trial included
      American Society of Anesthesiologists (ASA) physical status 1 and 2 adult
      patients, who were scheduled to undergo a surgical procedure of body surface.
      Subjects were randomized to one of the three groups: 1) preoperative CHO group,
      2) preoperative ORS group, and 3) control group. The primary outcome was the
      global QoR-40 administered 24 h after surgery. Intraoperative use of vasopressor,
      intraoperative body temperature changes, and postoperative nausea and vomiting
      (PONV) were also evaluated. RESULTS: We studied 134 subjects. The median
      [interquartile range (IQR)] global QoR-40 scores 24 h after the surgery were 187
      [177-197], 186 [171-200], and 184 [171-198] for the CHO, ORS, and control groups,
      respectively (p = 0.916). No significant differences existed between the groups
      regarding intraoperative vasopressor use during the surgery (p = 0.475).
      CONCLUSIONS: Results of the current study indicated that the preoperative
      administration of either CHO or ORS did not improve the quality of recovery in
      patients undergoing minimally invasive body surface surgery. TRIAL REGISTRATION:
      www.umin.ac.jp UMIN000009388 https://upload.umin.ac.jp/cgi-open
      bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000011029&langu
      ge=E.

PMID- 26317632
TI  - Bridging the Gap: Sella Turcica in Unilateral Cleft Lip and Palate Patients.
AB  - OBJECTIVES: The aims of this study were to analyze the prevalence of sella
      turcica bridging and to measure the size of the sella turcica on profile
      cephalograms in a homogenous group of surgically repaired unilateral cleft lip
      and palate (UCLP) patients. SETTING: Tertiary care center. DESIGN: Retrospective
      cross-sectional study. PATIENTS: Preorthodontic lateral cephalometric radiographs
      of 64 UCLP individuals between the ages of 16 and 29 years along with an equal
      number of age- and sex-matched skeletal Class I controls. MAIN OUTCOME MEASURES:
      The extent of calcification of the interclinoid ligament was quantified
      (completely calcified, partially calcified, no calcification) and mean values
      compared. Length, depth, and diameter of the sella turcica were also measured.
      The results were statistically analyzed using paired t test and Wilcoxon signed
      ranks test. RESULTS: Complete sella bridging of both type A (4.6%) and type B
      (21.7%) was significantly higher in UCLP patients. This has not been reported
      previously. Partial sella bridging was also higher in cleft patients as evaluated
      by two methods (42.18%, 39.06%). This study demonstrated a statistically
      significant decrease in all dimensions of sella turcica in UCLP patients.
      CONCLUSIONS: The UCLP patients apparently had higher predilection for sella
      turcica bridging. The dimensions of sella turcica were also seen to be
      significantly smaller than the control group. Defective proliferation and
      deviated pathways of neural crest cell migration as well as premature rupture of
      contact between neuroepithelium and oral ectoderm as postulated causes are
      discussed.

PMID- 26317630
TI  - Expression Analysis of Genes Involved in the RB/E2F Pathway in Astrocytic Tumors.
AB  - Astrocytic gliomas, which are derived from glial cells, are considered the most
      common primary neoplasias of the central nervous system (CNS) and are
      histologically classified as low grade (I and II) or high grade (III and IV).
      Recent studies have shown that astrocytoma formation is the result of the
      deregulation of several pathways, including the RB/E2F pathway, which is commonly
      deregulated in various human cancers via genetic or epigenetic mechanisms. On the
      basis of the assumption that the study of the mechanisms controlling the INK4/ARF
      locus can help elucidate the molecular pathogenesis of astrocytic tumors,
      identify diagnostic and prognostic markers, and help select appropriate clinical
      treatments, the present study aimed to evaluate and compare methylation patterns
      using bisulfite sequencing PCR and evaluate the gene expression profile using
      real-time PCR in the genes CDKN2A, CDKN2B, CDC6, Bmi-1, CCND1, and RB1 in
      astrocytic tumors. Our results indicate that all the evaluated genes are not
      methylated independent of the tumor grade. However, the real-time PCR results
      indicate that these genes undergo progressive deregulation as a function of the
      tumor grade. In addition, the genes CDKN2A, CDKN2B, and RB1 were underexpressed,
      whereas CDC6, Bmi-1, and CCND1 were overexpressed; the increase in gene
      expression was significantly associated with decreased patient survival.
      Therefore, we propose that the evaluation of the expression levels of the genes
      involved in the RB/E2F pathway can be used in the monitoring of patients with
      astrocytomas in clinical practice and for the prognostic indication of disease
      progression. 

PMID- 26317631
TI  - Genome-Wide Identification and Expression Analysis of the NAC Transcription
      Factor Family in Cassava.
AB  - NAC [no apical meristem (NAM), Arabidopsis transcription activation factor
      [ATAF1/2] and cup-shaped cotyledon (CUC2)] proteins is one of the largest groups
      of plant specific transcription factors and plays a crucial role in plant growth,
      development, and adaption to the environment. Currently, no information is known
      about the NAC family in cassava. In this study, 96 NAC genes (MeNACs) were
      identified from the cassava genome. Phylogenetic analysis of the NACs from
      cassava and Arabidopsis showed that MeNAC proteins can be clustered into 16
      subgroups. Gene structure analysis found that the number of introns of MeNAC
      genes varied from 0 to 5, with the majority of MeNAC genes containing two
      introns, indicating a small gene structure diversity of cassava NAC genes.
      Conserved motif analysis revealed that all of the identified MeNACs had the
      conserved NAC domain and/or NAM domain. Global expression analysis suggested that
      MeNAC genes exhibited different expression profiles in different tissues between
      wild subspecies and cultivated varieties, indicating their involvement in the
      functional diversity of different accessions. Transcriptome analysis demonstrated
      that MeNACs had a widely transcriptional response to drought stress and that they
      had differential expression profiles in different accessions, implying their
      contribution to drought stress resistance in cassava. Finally, the expression of
      twelve MeNAC genes was analyzed under osmotic, salt, cold, ABA, and H2O2
      treatments, indicating that cassava NACs may represent convergence points of
      different signaling pathways. Taken together, this work found some excellent
      tissue-specific and abiotic stress-responsive candidate MeNAC genes, which would
      provide a solid foundation for functional investigation of the NAC family, crop
      improvement and improved understanding of signal transduction in plants. These
      data bring new insight on the complexity of the transcriptional control of MeNAC
      genes and support the hypothesis that NACs play an important role in plant
      growth, development, and adaption of environment. 

PMID- 26317633
TI  - Bilateral Alveolar Distraction for Large Alveolar Defects: Case Report.
AB  - Distraction osteogenesis has become a very popular technique, as the ability to
      reconstruct combined deficiencies in bone and soft tissue makes this process
      unique and invaluable to all types of reconstructive surgeons. We document a case
      in which an intraoral tooth-borne distractor was designed and segmental alveolar
      distraction was performed in a large alveolar defect in a patient with bilateral
      cleft lip and palate. Cosmetic dentistry was performed to attain a pleasing
      result. This article aims at highlighting the use of distraction in large defects
      in which bone grafting only is not a suitable procedure.

PMID- 26317636
TI  - Autism: Oxytocin, serotonin, and social reward.
AB  - Over 70 years since the first description of the disease, disrupted social
      behavior remains a core clinical feature of autistic spectrum disorder. The
      complex etiology of the disorder portends the need for a better understanding of
      the brain mechanisms that enable social behaviors, particularly those that are
      relevant to autism which is characterized by a failure to develop peer
      relationships, difficulty with emotional reciprocity and imitative play, and
      disrupted language and communication skills. Toward this end, the current review
      will examine recent progress that has been made toward understanding the neural
      mechanisms underlying consociate social attachments. 

PMID- 26317637
TI  - (15)N and (31)P NMR Insights into Lactam-Lactim Tautomerism Activity Using cyclo
      MU-Imidopolyphosphates.
AB  - The effects of the molecular structure and solution pH on compounds prone to
      lactam-lactim tautomerism have been evaluated by (15)N NMR spectroscopy. The
      lactam-lactim tautomerism activities of cP3O6(NH)3(3-) and cP4O8(NH)4(4-) showed
      a significant pH dependence, with the process being inactivated under alkaline
      conditions because of the decrease in the number of hydrogen atoms by the
      deprotonation of the anions. The tautomerism was activated under the acidic
      conditions by the increase in the number of dissociative hydrogen atoms resulting
      from the protonation of the anions. cP3O6(NH)3(3-) has much more of a planar
      molecular structure than cP4O8(NH)4(4-), meaning that the hydrogen atoms in
      cP3O6(NH)3(3-) would be delocalized over the entire structure to a greater extent
      than those in cP4O8(NH)4(4-). This difference in the distribution of hydrogen
      atoms would result in the lactam-lactim tautomerism activity of cP3O6(NH)3(3-)
      being higher than that of cP4O8(NH)4(4-). The results have shown that the
      following factors are critical to the achievement of an efficient anhydrous
      proton conductor: (1) the regular molecular arrangement of highly planar
      molecules; (2) the existence of a large number of dissociative protons in a
      molecule; and (3) a molecular structure with a small energy barrier for the
      structural rearrangement required of the tautomerism process. 

PMID- 26317635
TI  - Prenatal Ambient Air Pollution, Placental Mitochondrial DNA Content, and Birth
      Weight in the INMA (Spain) and ENVIRONAGE (Belgium) Birth Cohorts.
AB  - BACKGROUND: Mitochondria are sensitive to environmental toxicants due to their
      lack of repair capacity. Changes in mitochondrial DNA (mtDNA) content may
      represent a biologically relevant intermediate outcome in mechanisms linking air
      pollution and fetal growth restriction. OBJECTIVE: We investigated whether
      placental mtDNA content is a possible mediator of the association between
      prenatal nitrogen dioxide (NO2) exposure and birth weight. METHODS: We used data
      from two independent European cohorts: INMA (n = 376; Spain) and ENVIRONAGE (n =
      550; Belgium). Relative placental mtDNA content was determined as the ratio of
      two mitochondrial genes (MT-ND1 and MTF3212/R3319) to two control genes (RPLP0
      and ACTB). Effect estimates for individual cohorts and the pooled data set were
      calculated using multiple linear regression and mixed models. We also performed a
      mediation analysis. RESULTS: Pooled estimates indicated that a 10-MUg/m3
      increment in average NO2 exposure during pregnancy was associated with a 4.9%
      decrease in placental mtDNA content (95% CI: -9.3, -0.3%) and a 48-g decrease
      (95% CI: -87, -9 g) in birth weight. However, the association with birth weight
      was significant for INMA (-66 g; 95% CI: -111, -23 g) but not for ENVIRONAGE (-20
      g; 95% CI: -101, 62 g). Placental mtDNA content was associated with significantly
      higher mean birth weight (pooled analysis, interquartile range increase: 140 g;
      95% CI: 43, 237 g). Mediation analysis estimates, which were derived for the INMA
      cohort only, suggested that 10% (95% CI: 6.6, 13.0 g) of the association between
      prenatal NO2 and birth weight was mediated by changes in placental mtDNA content.
      CONCLUSION: Our results suggest that mtDNA content can be one of the potential
      mediators of the association between prenatal air pollution exposure and birth
      weight. CITATION: Clemente DB, Casas M, Vilahur N, Begiristain H, Bustamante M,
      Carsin AE, Fernandez MF, Fierens F, Gyselaers W, Iniguez C, Janssen BG, Lefebvre
      W, Llop S, Olea N, Pedersen M, Pieters N, Santa Marina L, Souto A, Tardon A,
      Vanpoucke C, Vrijheid M, Sunyer J, Nawrot TS. 2016. Prenatal ambient air
      pollution, placental mitochondrial DNA content, and birth weight in the INMA
      (Spain) and ENVIRONAGE (Belgium) birth cohorts. Environ Health Perspect 124:659
      665; http://dx.doi.org/10.1289/ehp.1408981.

PMID- 26317638
TI  - Profiling the Psychological Training and Support Needs of Oncology Staff, and
      Evaluating the Effectiveness of a Level 2 Psychological Support Training Program
      Workshop.
AB  - The importance of training non-psychology healthcare professionals to offer
      psychological support to people with cancer is becoming increasingly recognized.
      This small-scale pilot project sought to identify the training and support needs
      of oncology staff and to evaluate the effectiveness of a Level 2 Psychological
      Support Training Program workshop. Semi-structured interviews with five members
      of multidisciplinary oncology staff identified that training needs were primarily
      around communication skills, recognizing and dealing with emotions, offering
      support and empathy, and self-care. Pre and post-training questionnaires
      developed with these themes in mind revealed that the Level 2 Training Program
      workshops run in this network of hospitals are effective in increasing
      participants' levels of perceived knowledge and confidence across each of these
      domains. Recommendations are made for further enhancing this effectiveness. 

PMID- 26317640
TI  - Increase of passive stiffness in adolescent idiopathic scoliosis.

PMID- 26317639
TI  - Mismatching between circulating strains and vaccine strains of influenza: Effect
      on Hajj pilgrims from both hemispheres.
AB  - The trivalent seasonal influenza vaccine is expected to provide optimum
      protection if the vaccine strains match the circulating strains. The effect of
      worldwide mismatch between the vaccine strains and extant strains on travelers
      attending Hajj pilgrimage is not known. Annually 2-3 million Muslims coming from
      north and south hemispheres congregate at Hajj in Mecca, Saudi Arabia, where
      intense congestion amplifies the risk of respiratory infection up to eight fold.
      In order to estimate, to what extent mismatching increases the risk of vaccine
      failure in Hajj pilgrims, we have examined the global data on influenza
      epidemiology since 2003, in light of the available data from Hajj. These data
      demonstrate that globally mismatching between circulating and vaccine strains has
      occurred frequently over the last 12 years, and the mismatch seems to have
      affected the Hajj pilgrims, however, influenza virus characteristics were studied
      only in a limited number of Hajj seasons. When the vaccines are different, dual
      vaccination of travelers by vaccines for southern and northern hemispheres should
      be considered for Hajj pilgrims whenever logistically feasible. Consideration
      should also be given to the use of vaccines with broader coverage, i.e.,
      quadrivalent, or higher immunogenicity. Continuous surveillance of influenza at
      Hajj is important.

PMID- 26317642
TI  - The Inhibitory Effects of Low-Dose Ionizing Radiation in IgE-Mediated Allergic
      Responses.
AB  - Ionizing radiation has different biological effects according to dose and dose
      rate. In particular, the biological effect of low-dose radiation is unclear. Low
      dose whole-body gamma irradiation activates immune responses in several ways.
      However, the effects and mechanism of low-dose radiation on allergic responses
      remain poorly understood. Previously, we reported that low-dose ionizing
      radiation inhibits mediator release in IgE-mediated RBL-2H3 mast cell activation.
      In this study, to have any physiological relevance, we investigated whether low
      dose radiation inhibits allergic responses in activated human mast cells (HMC
      1(5C6) and LAD2 cells), mouse models of passive cutaneous anaphylaxis and the
      late-phase cutaneous response. High-dose radiation induced cell death, but low
      dose ionizing radiation of <0.5 Gy did not induce mast cell death. Low-dose
      ionizing radiation that did not induce cell death significantly suppressed
      mediator release from human mast cells (HMC-1(5C6) and LAD2 cells) that were
      activated by antigen-antibody reaction. To determine the inhibitory mechanism of
      mediator released by low-dose ionizing radiation, we examined the phosphorylation
      of intracellular signaling molecules such as Lyn, Syk, phospholipase Cgamma, and
      protein kinase C, as well as the intracellular free Ca2+ concentration ([Ca2+]i).
      The phosphorylation of signaling molecules and [Ca2+]i following stimulation of
      FcepsilonRI receptors was inhibited by low dose ionizing radiation. In agreement
      with its in vitro effect, ionizing radiation also significantly inhibited
      inflammatory cells infiltration, cytokine mRNA expression (TNF-alpha, IL-4, IL
      13), and symptoms of passive cutaneous anaphylaxis reaction and the late-phase
      cutaneous response in anti-dinitrophenyl IgE-sensitized mice. These results
      indicate that ionizing radiation inhibits both mast cell-mediated immediate- and
      delayed-type allergic reactions in vivo and in vitro. 

PMID- 26317641
TI  - Induction of Non-Targeted Stress Responses in Mammary Tissues by Heavy Ions.
AB  - PURPOSE: Side effects related to radiation exposures are based primarily on the
      assumption that the detrimental effects of radiation occur in directly irradiated
      cells. However, several studies have reported over the years of radiation-induced
      non-targeted/ abscopal effects in vivo that challenge this paradigm. There is
      evidence that Cyclooxygenase-2 (COX2) plays an important role in modulating non
      targeted effects, including DNA damages in vitro and mutagenesis in vivo. While
      most reports on radiation-induced non-targeted response utilize x-rays, there is
      little information available for heavy ions. METHODS AND MATERIALS: Adult female
      transgenic gpt delta mice were exposed to an equitoxic dose of either carbon or
      argon particles using the Heavy Ion Medical Accelerator in Chiba (HIMAC) at the
      National Institute of Radiological Sciences (NIRS) in Japan. The mice were
      stratified into 4 groups of 5 animals each: Control; animals irradiated under
      full shielding (Sham-irradiated); animals receiving whole body irradiation
      (WBIR); and animals receiving partial body irradiation (PBIR) to the lower
      abdomen with a 1 x 1 cm2 field. The doses used in the carbon ion group (4.5 Gy)
      and in argon particle group (1.5 Gy) have a relative biological effectiveness
      equivalent to a 5 Gy dose of x-rays. 24 hours after irradiation, breast tissues
      in and out of the irradiated field were harvested for analysis. Induction of
      COX2, 8-hydroxydeoxyguanosine (8-OHdG), phosphorylated histone H2AX (gamma-H2AX),
      and apoptosis-related cysteine protease-3 (Caspase-3) antibodies were examined in
      the four categories of breast tissues using immunohistochemical techniques.
      Analysis was performed by measuring the intensity of more than 20 individual
      microscopic fields and comparing the relative fold difference. RESULTS: In the
      carbon ion group, the relative fold increase in COX2 expression was 1.01 in sham
      irradiated group (p > 0.05), 3.07 in PBIR (p < 0.05) and 2.50 in WBIR (p < 0.05),
      respectively, when compared with controls. The relative fold increase in 8-OHdG
      expression was 1.29 in sham-irradiated (p > 0.05), 11.31 in PBIR (p < 0.05) and
      11.79 in WBIR (p < 0.05), respectively, when compared with controls. A similar
      increase in gamma-H2AX expression was found in that, compared to controls, the
      increase was 1.41 fold in sham-irradiated (p > 0.05), 8.41 in PBIR (p < 0.05) and
      10.59 in WBIR (p < 0.05). Results for the argon particle therapy group showed a
      similar magnitude of changes in the various biological endpoints examined. There
      was no statistical significance observed in Caspase-3 expression among the 4
      groups. CONCLUSIONS: Our data show that both carbon and argon ions induced non
      targeted, out of field induction of COX2 and DNA damages in breast tissues. These
      effects may pose new challenges to evaluate the risks associated with radiation
      exposure and understanding radiation-induced side effects.

PMID- 26317643
TI  - Effects of Classroom Ventilation Rate and Temperature on Students' Test Scores.
AB  - Using a multilevel approach, we estimated the effects of classroom ventilation
      rate and temperature on academic achievement. The analysis is based on
      measurement data from a 70 elementary school district (140 fifth grade
      classrooms) from Southwestern United States, and student level data (N = 3109) on
      socioeconomic variables and standardized test scores. There was a statistically
      significant association between ventilation rates and mathematics scores, and it
      was stronger when the six classrooms with high ventilation rates that were
      indicated as outliers were filtered (> 7.1 l/s per person). The association
      remained significant when prior year test scores were included in the model,
      resulting in less unexplained variability. Students' mean mathematics scores
      (average 2286 points) were increased by up to eleven points (0.5%) per each liter
      per second per person increase in ventilation rate within the range of 0.9-7.1
      l/s per person (estimated effect size 74 points). There was an additional
      increase of 12-13 points per each 1 degrees C decrease in temperature within the
      observed range of 20-25 degrees C (estimated effect size 67 points). Effects of
      similar magnitude but higher variability were observed for reading and science
      scores. In conclusion, maintaining adequate ventilation and thermal comfort in
      classrooms could significantly improve academic achievement of students. 

PMID- 26317644
TI  - A measles virus selectively blind to signaling lymphocytic activation molecule
      shows anti-tumor activity against lung cancer cells.
AB  - Lung cancer cells, particularly those of non-small-cell lung cancer, are known to
      express Nectin-4. We previously generated a recombinant measles virus that uses
      Nectin-4 as its receptor but cannot bind its original principal receptor,
      signaling lymphocyte activation molecule (SLAM). This virus (rMV-SLAMblind)
      infects and kills breast cancer cells in vitro and in a subcutaneous xenograft
      model. However, it has yet to be determined whether rMV-SLAMblind is effective
      against other cancer types and in other tumor models that more closely represent
      disease. In this study, we analyzed the anti-tumor activity of this virus towards
      lung cancer cells using a modified variant that encodes green fluorescent protein
      (rMV-EGFP-SLAMblind). We found that rMV-EGFP-SLAMblind efficiently infected nine,
      human, lung cancer cell lines, and its infection resulted in reduced cell
      viability of six cell lines. Administration of the virus into subcutaneous tumors
      of xenotransplanted mice suppressed tumor growth. In addition, rMV-EGFP-SLAMblind
      could target scattered tumor masses grown in the lungs of xenotransplanted mice.
      These results suggest that rMV-SLAMblind is oncolytic for lung cancer and that it
      represents a promising tool for the treatment of this disease. 

PMID- 26317645
TI  - Prokineticin 2 (PROK2) is an important factor for angiogenesis in colorectal
      cancer.
AB  - The Prokineticin 2 (PROK2) is correlated with indispensable in maintaining the
      homeostasis of healthy human tissues. Herein, we examined the role of PROK2 in
      human colorectal cancer.After total RNA extraction from 6 colorectal cancer cell
      lines, we examined the expression of PROK2 mRNA. For investigating angiogenesis
      and tumor growth in mice, the PROK2 gene was transfected into colorectal cancer
      cell lines having low PROK2 mRNA expression. In addition, small interfering RNA
      (siRNA) was transfected into colorectal cancer cell lines having high PROK2 mRNA
      expression for investigation of angiogenesis and tumor growth in mice.From 6
      colorectal cancer cell lines studied, PROK2 mRNA expression was increased in 3
      cell lines. When the PROK2 gene was transfected into the colorectal cancer cell
      line with low PROK2 mRNA expression, angiogenesis and tumor growth in mice
      increased significantly compared to the cell line with the control vector.When
      PROK2 siRNA was transfected into colorectal cancer cell lines with high PROK2
      mRNA expression, angiogenesis and tumor growth in mice were suppressed
      significantly compared to the cell line with siRNA (control).This is the first
      report of the association of PROK2 as an angiogenic growth factor in colorectal
      cancer. 

PMID- 26317646
TI  - Automated tumor analysis for molecular profiling in lung cancer.
AB  - The discovery and clinical application of molecular biomarkers in solid tumors,
      increasingly relies on nucleic acid extraction from FFPE tissue sections and
      subsequent molecular profiling. This in turn requires the pathological review of
      haematoxylin & eosin (H&E) stained slides, to ensure sample quality, tumor DNA
      sufficiency by visually estimating the percentage tumor nuclei and tumor
      annotation for manual macrodissection. In this study on NSCLC, we demonstrate
      considerable variation in tumor nuclei percentage between pathologists,
      potentially undermining the precision of NSCLC molecular evaluation and
      emphasising the need for quantitative tumor evaluation. We subsequently describe
      the development and validation of a system called TissueMark for automated tumor
      annotation and percentage tumor nuclei measurement in NSCLC using computerized
      image analysis. Evaluation of 245 NSCLC slides showed precise automated tumor
      annotation of cases using Tissuemark, strong concordance with manually drawn
      boundaries and identical EGFR mutational status, following manual macrodissection
      from the image analysis generated tumor boundaries. Automated analysis of cell
      counts for % tumor measurements by Tissuemark showed reduced variability and
      significant correlation (p < 0.001) with benchmark tumor cell counts. This study
      demonstrates a robust image analysis technology that can facilitate the automated
      quantitative analysis of tissue samples for molecular profiling in discovery and
      diagnostics. 

PMID- 26317647
TI  - Myeloid-derived suppressor cells contribute to A2B adenosine receptor-induced
      VEGF production and angiogenesis in a mouse melanoma model.
AB  - Vascular endothelial growth factor (VEGF) is an angiogenic factor critically
      involved in tumor progression. Adenosine A2B receptor plays a pivotal role in
      promoting tumor growth. The aim of this study was to investigate the role of
      myeloid-derived suppressor cells (MDSCs) in the pro-angiogenic effects of A2B and
      to determine whether A2B blockade could enhance the effectiveness of anti-VEGF
      treatment. Mice treated with Bay60-6583, a selective A2B receptor agonist, showed
      enhanced tumor VEGF-A expression and vessel density. This effect was associated
      with accelerated tumor growth, which could be reversed with anti-VEGF treatment.
      Bay60-6583 increased the accumulation of tumor CD11b+Gr1+ cells. Depletion of
      MDSCs in mice significantly reduced A2B-induced VEGF production. However, A2B
      receptor stimulation did not directly regulate VEGF expression in isolated tumor
      myeloid cells. Mechanistically, Bay60-6583-treated melanoma tissues showed
      increased STAT3 activation. Inhibition of STAT3 significantly decreased the pro
      tumor activity of Bay60-6583 and reduced tumor VEGF expression. Pharmacological
      blockade of A2B receptor with PSB1115 significantly reduced tumor growth by
      inhibiting tumor angiogenesis and increasing T cells numbers within the tumor
      microenvironment. These effects are, at least in part, dependent on impaired
      tumor accumulation of Gr1+ cells upon A2B receptor blockade. PSB1115 increased
      the effectiveness of anti-VEGF treatment. 

PMID- 26317648
TI  - A poxviral-based cancer vaccine the transcription factor twist inhibits primary
      tumor growth and metastases in a model of metastatic breast cancer and improves
      survival in a spontaneous prostate cancer model.
AB  - Several transcription factors play a role in the alteration of gene expression
      that occurs during cancer metastasis. Twist expression has been shown to be
      associated with the hallmarks of the metastatic process, as well as poor
      prognosis and drug resistance in many tumor types. However, primarily due to
      their location within the cell and the lack of a hydrophobic groove required for
      drug attachment, transcription factors such as Twist are difficult to target with
      conventional therapies. An alternative therapeutic strategy is a vaccine
      comprised of a Modified vaccinia Ankara (MVA), incorporating the Twist transgene
      and a TRIad of COstimulatory Molecules (B7-1, ICAM-1, LFA-3; TRICOM). Here we
      characterize an MVA-TWIST/TRICOM vaccine that induced both CD4+ and CD8+ Twist
      specific T-cell responses in vivo. In addition, administration of this vaccine
      reduced both the primary tumor growth and metastasis in the 4T1 model of
      metastatic breast cancer. In the TRAMP transgenic model of spontaneous prostate
      cancer, MVA-TWIST/TRICOM alone significantly improved survival, and when combined
      with the androgen receptor antagonist enzalutamide, the vaccine further improved
      survival. These studies thus provide a rationale for the use of active
      immunotherapy targeting transcription factors involved in the metastatic process
      and for the combination of cancer vaccines with androgen deprivation. 

PMID- 26317649
TI  - Survival of primary, but not of cancer cells after combined Plk1-HDAC inhibition.
AB  - In the current study we examined the combination of SAHA and SBE13 in cancer and
      non-cancer cells. HeLa cells displayed a synergistically reduced cell
      proliferation, which was much weaker in hTERT-RPE1 or NIH-3T3 cells. Cell cycle
      distribution differed in HeLa, hTERT-RPE1 and NIH-3T3 cells. SAHA-treated HeLa
      cells showed slightly increasing cell numbers in G2/M phase, but after
      combination with SBE13 strongly elevated cell numbers in G2/M and S phase,
      accompanied by decreasing G0/G1 percentages. hTERT-RPE1 and NIH-3T3 cells showed
      strongly enriched cell numbers in G0/G1 phase. Western blot and quantitative real
      time analyses revealed reduced Plk1 mRNA and protein in all cells. p21 protein
      was strongly induced in cancer, but not in non-cancer cells, corresponding to a
      different localization in immunofluorescence studies. Additionally, these
      revealed an abundantly present pRb protein in HeLa cells after any treatment but
      almost completely vanished pRb staining in treated hTERT-RPE1 cells. These
      differences could be approved in Western blots against Parp and Caspase 3, which
      were activated in HeLa, but not in hTERT-RPE1 cells. Thus, we observed for the
      first time a differential effect of cancer versus non-cancer cells after
      treatment with SAHA and SBE13, which might be due to the dual role of p21. 

PMID- 26317650
TI  - An anti-EpCAM antibody EpAb2-6 for the treatment of colon cancer.
AB  - Epithelial cell adhesion molecule (EpCAM) is known to be overexpressed in
      epithelial cancers associated with enhanced malignant potential, particularly
      colorectal carcinoma (CRC) and head and neck squamous cell carcinoma (HNSCC).
      However, it is unknown whether progression of malignance can be directly
      inhibited by targeting EpCAM. Here, we have generated five novel monoclonal
      antibodies (mAbs) against EpCAM. One of these anti-EpCAM mAbs, EpAb2-6, was found
      to induce cancer cell apoptosis in vitro, inhibit tumor growth, and prolong the
      overall survival of both a pancreatic cancer metastatic mouse model and mice with
      human colon carcinoma xenografts. EpAb2-6 also increases the therapeutic efficacy
      of irinotecan, fluorouracil, and leucovorin (IFL) therapy in a colon cancer
      animal model and gemcitabine therapy in a pancreatic cancer animal model.
      Furthermore, EpAb2-6, which binds to positions Y95 and D96 of the EGF-II/TY
      domain of EpCAM, inhibits production of EpICD, thereby decreasing its
      translocation and subsequent signal activation. Collectively, our results
      indicate that the novel anti-EpCAM mAb can potentially be used for cancer
      targeted therapy. 

PMID- 26317651
TI  - Afatinib reverses multidrug resistance in ovarian cancer via dually inhibiting
      ATP binding cassette subfamily B member 1.
AB  - ABCB1-mediated multidrug resistance (MDR) remains a major obstacle to successful
      chemotherapy in ovarian cancer. Herein, afatinib at nontoxic concentrations
      significantly reversed ABCB1-mediated MDR in ovarian cancer cells in vitro (p <
      0.05). Combining paclitaxel and afatinib caused tumor regressions and tumor
      necrosis in A2780T xenografts in vivo. More interestingly, unlike reversible
      TKIs, afatinib had a distinctive dual-mode action. Afatinib not only inhibited
      the efflux function of ABCB1, but also attenuated its expression
      transcriptionally via down-regulation of PI3K/AKT and MAPK/p38-dependent
      activation of NF-kappaB. Furthermore, apart from a substrate binding domain,
      afatinib could also bind to an ATP binding domain of ABCB1 through forming
      hydrogen bonds with Gly533, Gly534, Lys536 and Ala560 sites. Importantly,
      mutations in these four binding sites of ABCB1 and the tyrosine kinase domain of
      EGFR were not correlated with the reversal activity of afatinib on MDR. Given
      that afatinib is a clinically approved drug, our results suggest combining
      afatinib with chemotherapeutic drugs in ovarian cancer. This study can facilitate
      the rediscovery of superior MDR reversal agents from molecular targeted drugs to
      provide a more effective and safer way of resensitizing MDR. 

PMID- 26317653
TI  - Rhino defines H3K9me3-marked piRNA clusters.

PMID- 26317652
TI  - Tumor suppressor NDRG2 inhibits glycolysis and glutaminolysis in colorectal
      cancer cells by repressing c-Myc expression.
AB  - Cancer cells use glucose and glutamine as the major sources of energy and
      precursor intermediates, and enhanced glycolysis and glutamimolysis are the major
      hallmarks of metabolic reprogramming in cancer. Oncogene activation and tumor
      suppressor gene inactivation alter multiple intracellular signaling pathways that
      affect glycolysis and glutaminolysis. N-Myc downstream regulated gene 2 (NDRG2)
      is a tumor suppressor gene inhibiting cancer growth, metastasis and invasion.
      However, the role and molecular mechanism of NDRG2 in cancer metabolism remains
      unclear. In this study, we discovered the role of the tumor suppressor gene NDRG2
      in aerobic glycolysis and glutaminolysis of cancer cells. NDRG2 inhibited glucose
      consumption and lactate production, glutamine consumption and glutamate
      production in colorectal cancer cells. Analysis of glucose transporters and the
      catalytic enzymes involved in glycolysis revealed that glucose transporter 1
      (GLUT1), hexokinase 2 (HK2), pyruvate kinase M2 isoform (PKM2) and lactate
      dehydrogenase A (LDHA) was significantly suppressed by NDRG2. Analysis of
      glutamine transporter and the catalytic enzymes involved in glutaminolysis
      revealed that glutamine transporter ASC amino-acid transporter 2 (ASCT2) and
      glutaminase 1 (GLS1) was also significantly suppressed by NDRG2. Transcription
      factor c-Myc mediated inhibition of glycolysis and glutaminolysis by NDRG2. More
      importantly, NDRG2 inhibited the expression of c-Myc by suppressing the
      expression of beta-catenin, which can transcriptionally activate C-MYC gene in
      nucleus. In addition, the growth and proliferation of colorectal cancer cells
      were suppressed significantly by NDRG2 through inhibition of glycolysis and
      glutaminolysis. Taken together, these findings indicate that NDRG2 functions as
      an essential regulator in glycolysis and glutaminolysis via repression of c-Myc,
      and acts as a suppressor of carcinogenesis through coordinately targeting glucose
      and glutamine transporter, multiple catalytic enzymes involved in glycolysis and
      glutaminolysis, which fuels the bioenergy and biomaterials needed for cancer
      proliferation and progress. 

PMID- 26317654
TI  - Testing Foundations of Biological Scaling Theory Using Automated Measurements of
      Vascular Networks.
AB  - Scientists have long sought to understand how vascular networks supply blood and
      oxygen to cells throughout the body. Recent work focuses on principles that
      constrain how vessel size changes through branching generations from the aorta to
      capillaries and uses scaling exponents to quantify these changes. Prominent
      scaling theories predict that combinations of these exponents explain how
      metabolic, growth, and other biological rates vary with body size. Nevertheless,
      direct measurements of individual vessel segments have been limited because
      existing techniques for measuring vasculature are invasive, time consuming, and
      technically difficult. We developed software that extracts the length, radius,
      and connectivity of in vivo vessels from contrast-enhanced 3D Magnetic Resonance
      Angiography. Using data from 20 human subjects, we calculated scaling exponents
      by four methods-two derived from local properties of branching junctions and two
      from whole-network properties. Although these methods are often used
      interchangeably in the literature, we do not find general agreement between these
      methods, particularly for vessel lengths. Measurements for length of vessels also
      diverge from theoretical values, but those for radius show stronger agreement.
      Our results demonstrate that vascular network models cannot ignore certain
      complexities of real vascular systems and indicate the need to discover new
      principles regarding vessel lengths. 

PMID- 26317655
TI  - Assessing Habitat Use by Snapper (Chrysophrys auratus) from Baited Underwater
      Video Data in a Coastal Marine Park.
AB  - Baited Underwater Video (BUV) systems have become increasingly popular for
      assessing marine biodiversity. These systems provide video footage from which
      biologists can identify the individual fish species present. Here we explore the
      relevance of spatial dependence and marine park boundaries while estimating the
      distribution and habitat associations of the commercially and recreationally
      important snapper species Chrysophrys auratus in Moreton Bay Marine Park during a
      period when new Marine National Parks zoned as no-take or "green" areas (i.e.,
      areas with no legal fishing) were introduced. BUV studies typically enforce a
      minimum distance among BUV sites, and then assume that observations from
      different sites are independent conditional on the measured covariates. In this
      study, we additionally incorporated the spatial dependence among BUV sites into
      the modelling framework. This modelling approach allowed us to test whether or
      not the incorporation of highly correlated environmental covariates or the
      geographic placement of BUV sites produced spatial dependence, which if
      unaccounted for could lead to model bias. We fitted Bayesian logistic models with
      and without spatial random effects to determine if the Marine National Park
      boundaries and available environmental covariates had an effect on snapper
      presence and habitat preference. Adding the spatial dependence component had
      little effect on the resulting model parameter estimates that emphasized positive
      association for particular coastal habitat types by snapper. Strong positive
      relationships between the presence of snapper and rock habitat, particularly
      rocky substrate composed of indurated freshwater sediments known as coffee rock,
      and kelp habitat reinforce the consideration of habitat availability in marine
      reserve design and the design of any associated monitoring programs. 

PMID- 26317656
TI  - An Engineered Split Intein for Photoactivated Protein Trans-Splicing.
AB  - Protein splicing is mediated by inteins that auto-catalytically join two
      separated protein fragments with a peptide bond. Here we engineered a genetically
      encoded synthetic photoactivatable intein (named LOVInC), by using the light
      sensitive LOV2 domain from Avena sativa as a switch to modulate the splicing
      activity of the split DnaE intein from Nostoc punctiforme. Periodic blue light
      illumination of LOVInC induced protein splicing activity in mammalian cells. To
      demonstrate the broad applicability of LOVInC, synthetic protein systems were
      engineered for the light-induced reassembly of several target proteins such as
      fluorescent protein markers, a dominant positive mutant of RhoA, caspase-7, and
      the genetically encoded Ca2+ indicator GCaMP2. Spatial precision of LOVInC was
      demonstrated by targeting activity to specific mammalian cells. Thus, LOVInC can
      serve as a general platform for engineering light-based control for modulating
      the activity of many different proteins. 

PMID- 26317658
TI  - Correction: Intrahepatic Cholestasis of Pregnancy (ICP) in U.S. Latinas and
      Chileans: Clinical features, Ancestry Analysis, and Admixture Mapping.

PMID- 26317659
TI  - Daily rhythms of clock gene expression and feeding behavior during the larval
      development in gilthead seabream, Sparus aurata.
AB  - Light is the main environmental time cue which synchronizes daily rhythms and the
      molecular clock of vertebrates. Indeed, alterations in photoperiod have profound
      physiological effects in fish (e.g. reproduction and early development). In order
      to identify the changes in clock genes expression in gilthead seabream larvae
      during ontogeny, three different photoperiods were tested: a regular 12L:12D
      cycle (LD), a continuous light 24L:0D (LL) and a two-phases photoperiod (LL + LD)
      in which the photoperiod changed from LL to LD on day 15 after hatching (dph).
      Larvae were sampled on 10, 18, 30 and 60 days post-hatch (dph) during a 24 h
      cycle. In addition to the expression of clock genes (clock, bmal1, cry1 and
      per3), food intake was measured. Under LD photoperiod, larvae feed intake and
      clock genes expression showed a rhythmic pattern with a strong light
      synchronization, with the acrophases occurring at the same hour in all tested
      ages. Under LL photoperiod, the larvae also showed a rhythmic pattern but the
      acrophases occurred at different times depending on the age, although at the end
      of the experiment (60 dph) clock genes expression and feed intake rhythms were
      similar to those larvae exposed to LD photoperiod. Moreover, the expression
      levels of bmal1 and cry1 were much lower than in LD photoperiod. Under the LL +
      LD photoperiod, the 10 dph larvae showed the same patterns as LL treatment while
      18 and 30 dph larvae showed the same patterns as LD treatment. These results
      revealed the presence of internal factors driving rhythmic physiological
      responses during larvae development under constant environmental conditions. The
      LL + LD treatment demonstrates the plasticity of the clock genes expression and
      the strong effect of light as synchronizer in developing fish larvae.

PMID- 26317657
TI  - Renal Function in Chinese HIV-Positive Individuals following Initiation of
      Antiretroviral Therapy.
AB  - AIM: To identify the prevalence and predictors of abnormal renal function among
      HIV-positive Chinese patients prior to antiretroviral therapy (ART) initiation
      and to evaluate subsequent changes in renal function after ART exposure. METHODS:
      We conducted a nationwide cohort study of subjects who enrolled in the national
      Chinese ART program from January 1, 2012 to December 31, 2012. We estimated the
      glomerular filtration rate (eGFR) of subjects prior to and after initiating ART.
      Risk factors for abnormal renal function, as defined by eGFR <60 ml/min/1.73m2,
      at baseline and follow-up were assessed by logistic regression and Cox
      proportional hazards regression models, respectively. RESULTS: Among 41,862
      subjects, at ART baseline, 3.3% had a baseline eGFR <60 ml/min/1.73m2 and 24.2%
      had eGFR = 60-90 ml/min/1.73m2. Adjusted baseline risk factors for baseline eGFR
      <60 ml/min/1.73m2 were older age (Adjusted odds ratio [AOR] = 5.19, 95%
      confidence interval [CI]: 4.52-5.67), female (AOR = 1.68, 95% CI: 1.47-1.93),
      hemoglobin <120g/L (AOR = 1.68, 95% CI: 1.47-1.93), blood glucose >6.1 mmol/L
      (AOR = 1.46, 95% CI: 1.25-1.72), and hepatitis C co-infection (AOR = 1.36, 95%
      CI: 1.06-1.73). Among subjects with baseline eGFR >90 ml/min/1.73m2, the
      incidence of the eGFR falling to <60 ml/min/1.73m2 was 0.92/100 person-years
      after a median of 15.0 months of ART. Being on a tenofovir with
      lopinavir/ritonavir regimen (Adjusted hazard ratio [AHR] = 3.02, 95% CI: 1.96
      4.66) and having an unsuppressed viral load (AHR = 2.70, 95% CI: 1.80-4.03) were
      independent predictors for eGFR <60 ml/min/1.73m2 after ART initiation as well as
      older age, female, and hemoglobin <120 g/L. CONCLUSION: A high proportion of HIV
      positive subjects in China presented with abnormal renal function prior to ART
      initiation. But the incidence of the eGFR decrease after ART was low. Patient
      renal function should be regularly monitored by eGFR before initiating and during
      ART.

PMID- 26317660
TI  - Aggregation Behavior of Fluorooctanols in Hydrocarbon Solvents.
AB  - The association behaviors of three 1-octanols (1-octanol:  C8OH; 1,1,2,2
      tetrahydrotridecafluorooctanol:  TFC8OH; and 1,1-dihydropentadecafluorooctanol: 
      DFC8OH) in two hydrocarbon solvents (n-hexane and benzene) were examined by
      vibration spectroscopy from 288.15 to 318.15 K. From the analysis of results with
      a mass action model, it was found that dimers and tetramers of 1-octanols
      coexisted with monomers in the n-hexane solution. These aggregates were formed by
      hydrogen bonding between the OH groups of 1-octanols. In the n-hexane solutions,
      an increase in the fluorination number of the 1-octanol molecule enhanced the
      intermolecular hydrogen bonding between the OH groups, but reduced the amounts of
      polymeric species. Conversely, in the benzene solution, the NIR experiment
      suggested that the OH groups of 1-octanols did not interact with other OH groups,
      but with the benzene molecules instead. It was found from (19)F NMR chemical
      shift measurements that the fluorooctanols in the benzene solution aggregated by
      interaction between the fluorocarbon chains instead of by hydrogen bonding. 

PMID- 26317661
TI  - Comparison of clinical characteristics in patients with bilateral and unilateral
      tinnitus.
AB  - CONCLUSION: Discomfort from bilateral tinnitus was more frequent and severe than
      that from unilateral tinnitus. Also, patients with bilateral tinnitus were
      significantly older and tended to have a longer duration of tinnitus than those
      with unilateral tinnitus. Background and subjects: Although bilateral tinnitus
      differs from unilateral tinnitus, their treatment is identical. Clinical
      characteristics associated with tinnitus, including tinnitograms, were
      retrospectively examined in 105 patients with unilateral tinnitus and 102 with
      bilateral tinnitus evaluated in the center between January 2012 and January 2014.
      This study compared the two groups to assess the characteristics differentiating
      their treatment. RESULTS: Mean age was significantly higher in patients with
      bilateral than unilateral tinnitus (p = 0.04), but gender distribution and
      duration of tinnitus were similar in the two groups. Both tinnitus handicap index
      (THI) and Beck depression index (BDI) values were significantly higher in
      patients with bilateral than unilateral tinnitus (p < 0.05 each). Rates of
      hyperacusis (p = 0.23), ear fullness (p = 0.16), and vertigo (p = 0.31) did not
      differ significantly between the two groups. Also, audiology test results,
      including tinnitograms, showed no significant differences.

PMID- 26317662
TI  - Echinacea-Based Dietary Supplement Does Not Increase Maximal Aerobic Capacity in
      Endurance-Trained Men and Women.
AB  - PURPOSE: To determine if an echinacea-based dietary supplement (EBS) provided at
      two different doses (a regular dose (RD), 8,000 mg/day, vs. a double dose (DD),
      16,000 mg/day) would increase erythropoietin (EPO) and other blood markers
      involved in improving aerobic capacity and maximal oxygen consumption (VO2max) in
      endurance-trained men. Secondly, to determine if any sex differences exist
      between male and female endurance-trained athletes. METHODS: Forty-five endurance
      athletes completed three visits during a 35-day intervention. Participants were
      randomized into placebo (PLA; n = 8 men, n = 7 women), RD of EBS (n = 7 men, n =
      8 women), or DD of EBS (n = 15 men) for the 35-day intervention period. At
      baseline, weight, body composition, and VO2max were measured. Blood was drawn to
      measure EPO, ferritin, red blood cells, white blood cells, hemoglobin, and
      hematocrit. At the mid-intervention visit, blood was collected. At the post
      intervention visit, all measurements from the baseline visit were obtained once
      again. RESULTS: There was a significant increase in VO2max for endurance-trained
      men in PLA (increase of 2.8 +/- 1.5 ml kg(-1) min(-1), p = .01) and RD of EBS
      (increase of 2.6 +/- 1.8 ml kg(-1) min(-1), p = .04), but not in DD of EBS (p =
      .96). Importantly, there was no difference in the change in VO2max between PLA
      and RD of EBS. For endurance-trained women, VO2max did not change in either
      treatment (PLA: -0.7 +/- 1.7 ml kg(-1) min(-1), p = .31; RD of EBS: -0.2 +/- 2.4
      ml kg(-1) min(-1), p = .80). There were no significant changes in any blood
      parameter across visits for any treatment group. CONCLUSIONS: This EBS should not
      be recommended as a means to improve performance in endurance athletes.

PMID- 26317663
TI  - Cancer cells exploit adaptive mitochondrial dynamics to increase tumor cell
      invasion.
AB  - Mitochondria are organelles that orchestrate a plethora of fundamental cellular
      functions that have been associated with various steps of tumor progression.
      However, we currently lack a mechanistic understanding of how mitochondrial
      dynamics, which reflects the organelles' exquisite heterogeneity in shape and
      spatial distribution, affects tumorigenesis. In a recent study, we uncovered a
      surprising new role of mitochondrial dynamics in response to PI3K therapy. We
      found that re-activation of Akt/mTOR signaling in tumor cells exposed to small
      molecule PI3K antagonists currently in the clinic triggered the transport of
      energetically active, elongated mitochondria to the cortical cytoskeleton of
      tumor cells. In turn, these repositioned mitochondria supported increased
      lamellipodia dynamics, faster turnover of focal adhesion complexes, heightened
      velocity and distance of random cell migration and increased tumor cell invasion.
      In this Extra View, we discuss the mechanistic basis of this paradoxical response
      to PI3K antagonists and propose possible strategies to disable mitochondrial
      adaptation. 

PMID- 26317665
TI  - Demineralized Dentin as a Semi-Rigid Barrier for Guiding Periodontal Tissue
      Regeneration.
AB  - BACKGROUND: Guided tissue regeneration (GTR) is an accepted approach in the
      correction of periodontal bone loss. Nonetheless, the deficiencies of commonly
      applied absorbable membrane, such as flexibility and limited osteoconductive and
      osteoinductive capability, still leave much room for improvement. Thus, the
      feasibility of applying demineralized dentin tissue to improve the therapeutic
      effect of GTR in periodontal regeneration was explored. METHODS: Demineralized
      dentin was harvested after acid treatment, and its physiochemical properties were
      assessed in terms of mineralization density, contact angle, three-point test, and
      cell attachment. Because of its similar characteristics with bone tissue, dentin
      that had been acid-treated for 6 hours was chosen to repair a periodontal defect
      using an induced-periodontitis canine model. Histologic measurements were taken
      to compare its therapeutic effects to an absorbable membrane group and an
      untreated group. RESULTS: The demineralized dentin displayed continually
      decreased hardness and density as the acid etching time was prolonged. Enhanced
      attachment and spreading of bone marrow mesenchymal stem cells were observed on
      the 6-hour processed dentin. Furthermore, in the demineralized dentin group, more
      periodontal tissues were newly formed compared with the biomembrane and untreated
      groups. CONCLUSION: Acid etching represents an easy and promising approach to
      obtain demineralized dentin with desirable properties, similar to bone, for
      clinical application to promote periodontal tissue regeneration.

PMID- 26317664
TI  - Different Blood Cell-Derived Transcriptome Signatures in Cows Exposed to
      Vaccination Pre- or Postpartum.
AB  - Periparturient cows have been found to reveal immunosuppression, frequently
      associated with increased susceptibility to uterine and mammary infections. To
      improve understanding of the causes and molecular regulatory mechanisms
      accounting for this phenomenon around calving, we examined the effect of an
      antigen challenge on gene expression modulation on cows prior to (BC) or after
      calving (AC) using whole transcriptome sequencing (RNAseq). The transcriptome
      analysis of the cows' blood identified a substantially higher number of loci
      affected in BC cows (2,235) in response to vaccination compared to AC cows (208)
      and revealed a divergent transcriptional profile specific for each group. In BC
      cows, a variety of loci involved in immune defense and cellular signaling
      processes were transcriptionally activated, whereas protein biosynthesis and
      posttranslational processes were tremendously impaired in response to
      vaccination. Furthermore, energy metabolism in the blood cells of BC cows was
      shifted from oxidative phosphorylation to the glycolytic system. In AC cows, the
      number and variety of regulated pathways involved in immunomodulation and
      maintenance of immnunocompetence are considerably lower after vaccination, and
      upregulation of arginine degradation was suggested as an immunosuppressive
      mechanism. Elevated transcript levels of erythrocyte-specific genes involved in
      gas exchange processes were a specific transcriptional signature in AC cows
      pointing to hematopoiesis activation. The divergent and substantially lower
      magnitude of transcriptional modulation in response to vaccination in AC cows
      provides evidence for a suppressed immune capacity of early lactating cows on the
      molecular level and demonstrates that an efficient immune response of cows is
      related to their physiological and metabolic status. 

PMID- 26317666
TI  - Deposition of graphene nanomaterial aerosols in human upper airways.
AB  - Graphene nanomaterials have attracted wide attention in recent years on their
      application to state-of-the-art technology due to their outstanding physical
      properties. On the other hand, the nanotoxicity of graphene materials also has
      rapidly become a serious concern especially in occupational health. Graphene
      naomaterials inevitably could become airborne in the workplace during
      manufacturing processes. The inhalation and subsequent deposition of graphene
      nanomaterial aerosols in the human respiratory tract could potentially result in
      adverse health effects to exposed workers. Therefore, investigating the
      deposition of graphene nanomaterial aerosols in the human airways is an
      indispensable component of an integral approach to graphene occupational health.
      For this reason, this study carried out a series of airway replica deposition
      experiments to obtain original experimental data for graphene aerosol airway
      deposition. In this study, graphene aerosols were generated, size classified, and
      delivered into human airway replicas (nasal and oral-to-lung airways). The
      deposition fraction and deposition efficiency of graphene aerosol in the airway
      replicas were obtained by a novel experimental approach. The experimental results
      acquired showed that the fractional deposition of graphene aerosols in airway
      sections studied were all less than 4%, and the deposition efficiency in each
      airway section was generally lower than 0.03. These results indicate that the
      majority of the graphene nanomaterial aerosols inhaled into the human respiratory
      tract could easily penetrate through the head airways as well as the upper part
      of the tracheobronchial airways and then transit down to the lower lung airways,
      where undesired biological responses might be induced. 

PMID- 26317667
TI  - Rhodamine-Functionalized Graphene Quantum Dots for Detection of Fe(3+) in Cancer
      Stem Cells.
AB  - A turn-on orange-red fluorescent nanosensor based on rhodamine B derivative
      functionalized graphene quantum dots (RBD-GQDs) has been successfully synthesized
      for Fe(3+) detection with high sensitivity and selectivity. By connecting with
      GQDs, the water solubility, sensitivity, photostability, and biocompatibility of
      RBD are drastically improved. The most distinctive feature of the RBD-GQDs, which
      sets them apart from other previously reported fluorophores or GQDs, is that they
      with the detection limits as low as 0.02 MUM are demonstrated as a Fe(3+) turn-on
      fluorescent nanosensor in cancer stem cells. Fe(3+) binding to such GQDs (RBD
      GQDs-Fe(3+)) with orange-red fluorescence of 43% quantum yield were demonstrated
      to be the biomarkers for cancer stem cell imaging. 

PMID- 26317668
TI  - Establishing Functional Relationships between Abiotic Environment, Macrophyte
      Coverage, Resource Gradients and the Distribution of Mytilus trossulus in a
      Brackish Non-Tidal Environment.
AB  - Benthic suspension feeding mussels are an important functional guild in coastal
      and estuarine ecosystems. To date we lack information on how various
      environmental gradients and biotic interactions separately and interactively
      shape the distribution patterns of mussels in non-tidal environments. Opposing to
      tidal environments, mussels inhabit solely subtidal zone in non-tidal waterbodies
      and, thereby, driving factors for mussel populations are expected to differ from
      the tidal areas. In the present study, we used the boosted regression tree
      modelling (BRT), an ensemble method for statistical techniques and machine
      learning, in order to explain the distribution and biomass of the suspension
      feeding mussel Mytilus trossulus in the non-tidal Baltic Sea. BRT models
      suggested that (1) distribution patterns of M. trossulus are largely driven by
      separate effects of direct environmental gradients and partly by interactive
      effects of resource gradients with direct environmental gradients. (2) Within its
      suitable habitat range, however, resource gradients had an important role in
      shaping the biomass distribution of M. trossulus. (3) Contrary to tidal areas,
      mussels were not competitively superior over macrophytes with patterns indicating
      either facilitative interactions between mussels and macrophytes or co-variance
      due to common stressor. To conclude, direct environmental gradients seem to
      define the distribution pattern of M. trossulus, and within the favourable
      distribution range, resource gradients in interaction with direct environmental
      gradients are expected to set the biomass level of mussels. 

PMID- 26317669
TI  - Maternal Postpartum Hospitalization Following Assisted Reproductive Technology
      Births.

PMID- 26317670
TI  - Challenges Analyzing Gypsum on Mars by Raman Spectroscopy.
AB  - Raman spectroscopy can provide chemical information about organic and inorganic
      substances quickly and nondestructively with little to no sample preparation,
      thus making it an ideal instrument for Mars rover missions. The ESA ExoMars
      planetary mission scheduled for launch in 2018 will contain a miniaturized Raman
      spectrometer (RLS) as part of the Pasteur payload operating with a continuous
      wave (CW) laser emitting at 532 nm. In addition, NASA is independently developing
      two miniaturized Raman spectrometers for the upcoming Mars 2020 rover mission,
      one of which is a remote (stand-off) Raman spectrometer that uses a pulse-gated
      532 nm excitation system (SuperCam). The other is an in situ Raman spectrometer
      that employs a CW excitation laser emitting at 248.6 nm (SHERLOC). Recently, it
      has been shown with analyses by Curiosity that Gale Crater contains significantly
      elevated concentrations of transition metals such as Cr and Mn. Significantly,
      these transition metals are known to undergo fluorescence emission in the visible
      portion of the electromagnetic spectrum. Consequently, samples containing these
      metals could be problematic for the successful acquisition of fluorescence-free
      Raman spectra when using a CW 532 nm excitation source. Here, we investigate one
      analog environment, with a similar mineralogy and sedimentology to that observed
      in martian environments, as well as elevated Cr contents, to ascertain the best
      excitation wavelength to successfully collect fluorescence-free spectra from Mars
      like samples. Our results clearly show that CW near-infrared laser excitation
      emitting at 785 nm is better suited to the collection of fluorescence-free Raman
      spectra than would be a CW laser emitting at 532 nm.

PMID- 26317671
TI  - From a Somatotopic to a Spatiotopic Frame of Reference for the Localization of
      Nociceptive Stimuli.
AB  - To react efficiently to potentially threatening stimuli, we have to be able to
      localize these stimuli in space. In daily life we are constantly moving so that
      our limbs can be positioned at the opposite side of space. Therefore, a
      somatotopic frame of reference is insufficient to localize nociceptive stimuli.
      Here we investigated whether nociceptive stimuli are mapped into a spatiotopic
      frame of reference, and more specifically a peripersonal frame of reference,
      which takes into account the position of the body limbs in external space, as
      well as the occurrence of external objects presented near the body. Two temporal
      order judgment (TOJ) experiments were conducted, during which participants had to
      decide which of two nociceptive stimuli, one applied to either hand, had been
      presented first while their hands were either uncrossed or crossed over the body
      midline. The occurrence of the nociceptive stimuli was cued by uninformative
      visual cues. We found that the visual cues prioritized the perception of
      nociceptive stimuli applied to the hand laying in the cued side of space,
      irrespective of posture. Moreover, the influence of the cues was smaller when
      they were presented far in front of participants' hands as compared to when they
      were presented in close proximity. Finally, participants' temporal sensitivity
      was reduced by changing posture. These findings are compatible with the existence
      of a peripersonal frame of reference for the localization of nociceptive stimuli.
      This allows for the construction of a stable representation of our body and the
      space closely surrounding our body, enabling a quick and efficient reaction to
      potential physical threats. 

PMID- 26317672
TI  - Neurocognitive Changes Associated With Surgical Resection of Left and Right
      Temporal Lobe Glioma.
AB  - BACKGROUND: Little is known regarding the neurocognitive impact of temporal lobe
      tumor resection. OBJECTIVE: To clarify subacute surgery-related changes in
      neurocognitive functioning (NCF) in patients with left (LTL) and right (RTL)
      temporal lobe glioma. METHODS: Patients with glioma in the LTL (n = 45) or RTL (n
      = 19) completed comprehensive pre- and postsurgical neuropsychological
      assessments. NCF was analyzed with 2-way mixed design repeated-measures analysis
      of variance, with hemisphere (LTL or RTL) as an independent between-subjects
      factor and pre- and postoperative NCF as a within-subjects factor. RESULTS: About
      60% of patients with LTL glioma and 40% with RTL lesions exhibited significant
      worsening on at least 1 NCF test. Domains most commonly impacted included verbal
      memory and executive functioning. Patients with LTL tumor showed greater decline
      than patients with RTL tumor on verbal memory and confrontation naming tests.
      Nonetheless, over one-third of patients with RTL lesions also showed verbal
      memory decline. CONCLUSION: In patients with temporal lobe glioma, NCF decline in
      the subacute postoperative period is common. As expected, patients with LTL tumor
      show more frequent and severe decline than patients with RTL tumor, particularly
      on verbally mediated measures. However, a considerable proportion of patients
      with RTL tumor also exhibit decline across various domains, even those typically
      associated with left hemisphere structures, such as verbal memory. While patients
      with RTL lesions may show even greater decline in visuospatial memory, this
      domain was not assessed. Nonetheless, neuropsychological assessment can identify
      acquired deficits and help facilitate early intervention in patients with
      temporal lobe glioma.

PMID- 26317673
TI  - Surgical Clipping of Very Small Unruptured Intracranial Aneurysms: A Multicenter
      International Study.
AB  - BACKGROUND: Treatment of very small unruptured intracranial aneurysms (VSUIAs,
      defined as <=3 mm) can be indicated in selected circumstances. The feasibility
      and outcomes of endovascular therapy for VSUIAs have been recently published;
      however, the efficacy and complication rate of surgical clipping has not been
      reported in any large series to date. OBJECTIVE: We conducted a multicenter study
      to examine surgical outcomes for VSUIAs. METHODS: All consecutive patients
      undergoing surgery for a VSUIA in 4 neurosurgical centers between October 2001
      and December 2012 were retrospectively analyzed. RESULTS: In the study, 183
      patients (128 women, mean age 51.3 years) were treated with 190 procedures for a
      total of 228 aneurysms. Most were anterior circulation aneurysms (n = 215). The
      majority were directly clipped (n = 222, 97.4%), with coagulation or wrapping in
      the remainder. After 1 reoperation for incomplete clipping, postoperative imaging
      of 225 aneurysms confirmed complete occlusion in 221 (98.2%), 1 neck remnant
      (0.44%), and 3 partial occlusions (1.3%). Mortality was 0%. Early postoperative
      neurological deficit developed in 12 patients (6.6%); posterior circulation
      location was a significant risk factor for early neurological deficit (P < .001).
      Middle cerebral artery aneurysms had the lowest rate of postoperative deficits at
      1.5% (P = .023). After the initial 30-day perioperative period, all deficits
      related to treatment of posterior circulation aneurysms recovered; overall
      neurological morbidity decreased to 2.7% with no mortality. CONCLUSION: VSUIA
      clipping is highly effective and is associated with a low morbidity rate. For
      VSUIAs selected for treatment, our data support surgical clipping as the modality
      of choice.

PMID- 26317675
TI  - In Reply: Neurodegeneration and Sport: Dated and Lacking Full Disclosure.

PMID- 26317676
TI  - Endovascular Management of Deep Arteriovenous Malformations: Single Institution
      Experience in 22 Consecutive Patients.
AB  - BACKGROUND: The management of arteriovenous malformations (AVMs) in the basal
      ganglia, insula, and thalamus is demanding for all treatment modalities.
      OBJECTIVE: To define safety and outcomes of embolization used as a stand-alone
      therapy for deep-seated AVMs. METHODS: A cohort of 22 patients with AVMs located
      in the basal ganglia, thalamus, and insula who underwent embolization between
      January 2008 and December 2013. RESULTS: Eighteen of 22 (82%) patients had
      anatomic exclusion. The mean size was 2.98 +/- 1.28 cm, and the mean number of
      sessions was 2.1 per patient. Most patients presented with hemorrhage (82%, n =
      18), and 3 (14%) patients were in a deteriorated neurological status (modified
      Rankin Scale >2) at presentation. Sixty-eight percent of ruptured AVMs had size
      <=3 cm. A single transarterial approach was performed in 9 (41%) cases, double
      catheterization was used in 4 (18%), and the transvenous approach was required in
      8 (36%) cases. Procedure-related complications were registered in 3 (14%) cases.
      One death was associated with treatment, and complementary radiosurgery was
      required in 2 (9%) patients. CONCLUSION: Embolization therapy appears to be safe
      and potentially curative for certain deep AVMs. Our results demonstrate a high
      percentage of anatomic obliteration with rates of complications that may approach
      radiosurgery profile. In particular, embolization as stand-alone therapy is most
      suitable to deep AVMs with small nidus size (<=3 cm) and/or associated with
      single venous drainage in which microsurgery might not be indicated.

PMID- 26317678
TI  - Microsurgical Management of Eagle Syndrome With Ipsilateral Carotid-Ophthalmic
      Aneurysm: 3-Dimensional Operative Video.

PMID- 26317680
TI  - Water Load Test in Childhood Functional Abdominal Pain: No Relation to Food
      Intake and Nutritional Status.
AB  - This cross-sectional study evaluates the relations between the water load test in
      childhood functional gastrointestinal disorders with food intake and nutritional
      status. Patients with functional dyspepsia required a lower maximum water intake
      to produce fullness (n = 11, median = 380 mL) than patients with irritable bowel
      syndrome (n = 10, median = 695 mL) or functional abdominal pain (n = 10, median =
      670 mL) (P < 0.05). Among patients who ingested <=560 mL (n = 17) or >560 mL (n =
      14) in the water load test, there was no relation between the maximum drinking
      capacity and food intake, body mass index, or height.

PMID- 26317681
TI  - DCl Transport through Dodecyl Sulfate Films on Salty Glycerol: Effects of
      Seawater Ions on Gas Entry.
AB  - Gas-liquid scattering experiments were employed to measure the entry and
      dissociation of the acidic gas DCl into salty glycerol coated with dodecyl
      sulfate ions (DS(-) = CH3(CH2)11OSO3(-)). Five sets of salty solutions were
      examined: 0.25 and 0.5 M NaCl, 0.25 M MgCl2, 0.25 M CaCl2, and artificial sea
      salt. DS(-) bulk concentrations were varied from 0 to 11 mM, generating DS(-)
      surface coverages of up to 34% of a compact monolayer, as determined by surface
      tension and argon scattering measurements. DS(-) surface segregation is enhanced
      by the dissolved salts in the order MgCl2 ~ CaCl2 > sea salt > NaCl. We find that
      DCl penetration through the dodecyl chains decreases at first gradually and then
      sharply as more chains segregate to the surface, dropping from 70% entry on bare
      glycerol to 11% for DS(-) surface concentrations of 1.8 * 10(14) cm(-2). When
      plotted against DS(-) surface concentration, the DCl entry probabilities fall
      within a single band for all solutions. These observations imply that the
      monovalent Na(+) and divalent Ca(2+) and Mg(2+) ions do not bind differently
      enough to the ROSO3(-) headgroup to significantly alter the diffusive passage of
      DCl molecules through the dodecyl chains at the same DS(-) chain density. The
      chief difference among the salts is the greater propensity for the divalent salts
      to expel the soluble ionic surfactant to the surface. 

PMID- 26317679
TI  - Genetics of systemic sclerosis: recent advances.
AB  - PURPOSE OF REVIEW: Large-scale and follow-up genetic association studies in
      systemic sclerosis (SSc) have implicated over 40 regions in disease risk, 15 of
      which with robust associations. Nevertheless, the causal variants and the
      functional mechanisms underlying the genetic associations remain elusive, and the
      reasons for the higher disease burden in African Americans unknown. Incorporating
      tools from diverse fields is beginning to unveil the role of genetic diversity
      and regulatory variation in SSc susceptibility. This review will summarize recent
      advances in SSc genetics, including autoimmune disease overlap, evidence of
      natural selection, and current progress towards the dissection of the functional
      role of associated risk variants. RECENT FINDINGS: In the past year, multiple
      large-scale studies reported novel strong and suggestive SSc associations. These
      results, coupled with the regions shared with other autoimmune diseases,
      emphasize the role of dysregulation of immune pathways as a key causative factor
      in SSc pathogenesis. Strong evidence implicates natural selection as a mechanism
      contributing to the maintenance of some of these SSc alleles in the population.
      Studies integrating genomic, transcriptomic, and epigenomic datasets in specific
      cell types to identify causal autoimmune disease variants are emerging. SUMMARY:
      The identification and comprehensive understanding of the factors and mechanisms
      contributing to SSc will contribute to improved diagnosis and disease management.

PMID- 26317682
TI  - Transient Absorption Measurements on Anisotropic Monolayer ReS2.
AB  - Anisotropic optical and transport properties of monolayer ReS2 fabricated by
      mechanical exfoliation are reported. Transient absorption measurements with
      different polarization configurations and sample orientations reveal that the
      absorption coefficient and transient absorption are both anisotropic, with
      maximal and minimal values occurring when the light polarization is parallel and
      perpendicular to the Re atomic chains, respectively. The maximal values are about
      a factor of 2.5 of the minimal values. By resolving the spatiotemporal dynamics
      of excitons, it is found that the diffusion coefficient of excitons moving along
      Re atomic chains is about 16 cm(2) s(-1) at room temperature, which is about a
      factor of three larger than those moving perpendicular to that direction. An
      exciton lifetime of 40 ps is also extracted. These findings establish monolayer
      ReS2 as an anisotropic 2D transition metal dichalcogenide. 

PMID- 26317683
TI  - Phase I study evaluating the safety and efficacy of oral panobinostat in
      combination with radiotherapy or chemoradiotherapy in patients with inoperable
      stage III non-small-cell lung cancer.
AB  - Panobinostat is a radiosensitizing agent and targets the epigenetics of
      malignancy. This phase I study evaluated the safety and efficacy of combining
      oral panobinostat with radiotherapy (RT) or chemoradiotherapy (CRT) in patients
      with inoperable stage III non-small-cell lung cancer. This study had a parallel
      dose-escalating design combining oral panobinostat twice a week (dose escalations
      20, 30, 45 mg) with either palliative RT (group A) or radical CRT (group B) using
      a standard chemotherapy protocol of cisplatin and etoposide. In group A (RT),
      nine recruited patients received treatment with oral panobinostat (doses 20, 30,
      45 mg) with RT. Two serious adverse events, rapid atrial fibrillation and tracheo
      oesophageal fistula, were not attributable to study treatment. The most common
      grade 3/4 toxicities were thrombocytopenia and lymphopenia, which resolved
      promptly after cessation of panobinostat. The disease control rate was 66%, the
      progression-free survival was 3 months and the median overall survival was 9
      months. In group B (CRT), panobinostat dose was not escalated beyond 20 mg
      because of infection-related complications. Serious adverse events included
      opportunistic infection associated with treatment-related lymphopenia and febrile
      neutropenia without a source. One patient had cerebral infarct that was not
      attributed to study treatment. All patients achieved a partial response to
      treatment. At 33 months of follow-up, all patients were still alive. Panobinostat
      can be combined with palliative-dose RT at doses up to 45 mg twice a week with
      tolerable toxicity. Dose-limiting toxicities prevented the dose escalation of the
      panobinostat with CRT. 

PMID- 26317684
TI  - Species- and gender-dependent differences in the glucuronidation of a flavonoid
      glucoside and its aglycone determined using expressed UGT enzymes and microsomes.
AB  - Flavonoids occur naturally as glucosides and aglycones. Their common phenolic
      hydroxyl groups may trigger extensive UDP-glucuronosyltransferase (UGT)-
      catalysed metabolism. Unlike aglycones, glucosides contain glucose moieties.
      However, the influence of these glucose moieties on glucuronidation of glucosides
      and aglycones remains unclear. In this study, the flavonoid glucoside tilianin
      and its aglycone acacetin were used as model compounds. The glucuronidation
      characteristics and enzyme kinetics of tilianin and acacetin were compared using
      human UGT isoforms, liver microsomes and intestinal microsomes obtained from
      different animal species. Tilianin and acacetin were metabolized into different
      glucuronides, with UGT1A8 produced as the main isoform. Assessment of enzyme
      kinetics in UGT1A8, human liver microsomes and human intestinal microsomes
      revealed that compared with tilianin, acacetin displayed lower Km (0.6-, 0.7- and
      0.6-fold, respectively), higher Vmax (20-, 60- and 230-fold, respectively) and
      higher clearance (30-, 80- and 300-fold, respectively). Furthermore,
      glucuronidation of acacetin and tilianin showed significant species- and gender
      dependent differences. In conclusion, glucuronidation of flavonoid aglycones is
      faster than that of glucosides in the intestine and the liver. Understanding the
      metabolism and species- and gender-dependent differences between glucosides and
      aglycones is crucial for the development of drugs from flavonoids.

PMID- 26317685
TI  - Associations between socioeconomic position and correlates of sedentary behaviour
      among youth: a systematic review.
AB  - Existing research evidence indicates that children and adolescents of parents
      with a low socioeconomic position spend more time on sedentary behaviour than
      their counterparts. However, the mechanisms driving these differences remain
      poorly understood. The main aim of this systematic review was to summarize the
      evidence regarding the association between socioeconomic position and correlates
      of sedentary behaviour among youth (0-18 years) from developed countries. The
      literature search was conducted using MEDLINE, Embase, CINAHL and PsycINFO. A
      total of 37 studies were included. All but three studies examined screen-based
      sedentary behaviours only. Methodological quality ranged from low to moderate.
      Education was the most commonly used indicator of socioeconomic position,
      followed by income. Socioeconomic position was inversely related to the presence
      of a TV in the child's bedroom, parental modelling for TV viewing, parental co
      viewing and eating meals in front of the TV. We found no/indeterminate evidence
      for an association between socioeconomic position and rules and regulations about
      screen time. The findings suggest possible factors that could be targeted in
      future intervention studies to decrease screen-based sedentary behaviour in lower
      socioeconomic groups in particular. 

PMID- 26317686
TI  - Particle transport in the human respiratory tract: formulation of a nodal inverse
      distance weighted Eulerian-Lagrangian transport and implementation of the Wind
      Kessel algorithm for an oral delivery.
AB  - This paper is the first in a series wherein efficient computational methods are
      developed and implemented to accurately quantify the transport, deposition, and
      clearance of the microsized particles (range of interest: 2 to 10 um) in the
      human respiratory tract. In particular, this paper (part I) deals with (i)
      development of a detailed 3D computational finite volume mesh comprising of the
      NOPL (nasal, oral, pharyngeal and larynx), trachea and several airway
      generations; (ii) use of CFD Research Corporation's finite volume Computational
      Biology (CoBi) flow solver to obtain the flow physics for an oral inhalation
      simulation; (iii) implement a novel and accurate nodal inverse distance weighted
      Eulerian-Lagrangian formulation to accurately obtain the deposition, and (iv)
      development of Wind-Kessel boundary condition algorithm. This new Wind-Kessel
      boundary condition algorithm allows the 'escaped' particles to reenter the airway
      through the outlets, thereby to an extent accounting for the drawbacks of having
      a finite number of lung generations in the computational mesh. The deposition
      rates in the NOPL, trachea, the first and second bifurcation were computed, and
      they were in reasonable accord with the Typical Path Length model. The
      quantitatively validated results indicate that these developments will be useful
      for (i) obtaining depositions in diseased lungs (because of asthma and COPD), for
      which there are no empirical models, and (ii) obtaining the secondary clearance
      (mucociliary clearance) of the deposited particles. Copyright (c) 2015 John Wiley
      & Sons, Ltd.

PMID- 26317687
TI  - Monodisperse Copper Chalcogenide Nanocrystals: Controllable Synthesis and the
      Pinning of Plasmonic Resonance Absorption.
AB  - Controllable synthesis of copper chalcogenide nanocrystals (NCs), including
      desired geometry, composition and surrounding environment, is of high
      significance for the modulation of their optoelectronic response and the
      corresponding applications. Herein, copper nitride nanoparticles have been used
      as "uncontaminated" copper precursors to synthesize copper chalcogenide NCs with
      high monodispersity through a one-pot strategy. In this protocol, the sizes and
      compositions of NCs can be readily controlled by varying the ratio of the
      precursors. For Cu(2-x)S NCs with different diameters, the size variations are
      all smaller than 5.6%. Furthermore, the plasmonic properties of the copper
      chalcogenide NCs are investigated under a steady state by tuning the plasmonic
      resonance absorption band to a limiting condition (denoted "pinning" phenomena).
      It is observed that the pinning frequency increases (from 1.09 to 1.23 eV) with
      the increment of the NC size (from 5.4 +/- 0.3 to 11.1 +/- 0.4 nm), explained by
      introducing surface scattering. Meanwhile, the frequencies of ternary alloyed
      copper sulfide selenide NCs blue-shift from 0.90 to 1.00 eV with the increase of
      selenium content from 11% to 66%, which is related to the effective mass of free
      carriers. Additionally, the plasmonic absorption bands of Cu(2-x)S NCs
      encapsulated by two single-layer graphene pin at 1525-1550 nm during the
      oxidation process, which is influenced by both the dielectric constant and redox
      potential of the surrounding environment. This study demonstrates the
      controllable synthesis and precise fundamental plasmonic properties of the copper
      chalcogenide NCs, ensuring the potential plasmonic-related techniques with high
      efficiency, accuracy and excellent spatial resolution.

PMID- 26317689
TI  - Small for size: Laboratory perspective.

PMID- 26317688
TI  - No role for human papillomavirus infection in oral cancers in a region in
      southern India.
AB  - Oral cancer is a major public health issue in India with ~ 77,000 new cases and
      52,000 deaths yearly. Paan chewing, tobacco and alcohol use are strong risk
      factors for this cancer in India. Human papillomaviruses (HPVs) are also related
      to a subset of head and neck cancers (HNCs). We examined the association between
      oral HPV and oral cancer in a sample of Indian subjects participating in a
      hospital-based case-control study. We recruited incident oral cancer cases (N =
      350) and controls frequency-matched by age and sex (N = 371) from two main
      referral hospitals in Kerala, South India. Sociodemographic and behavioral data
      were collected by interviews. Epithelial cells were sampled using Oral CDx(r)
      brushes from the oral cancer site and the normal mucosa. Detection and genotyping
      of 36 HPV genotypes were done using a polymerase chain reaction protocol. Data
      collection procedures were performed by qualified dentists via a detailed
      protocol with strict quality control, including independent HPV testing in India
      and Canada. HPV DNA was detected in none of the cases or controls. Associations
      between oral cancer and risk factors usually associated with HPV infection, such
      as oral sex and number of lifetime sexual partners, were examined by logistic
      regression and were not associated with oral cancer. Lack of a role for HPV
      infection in this study may reflect cultural or religious characteristics
      specific to this region in India that are not conducive to oral HPV transmission.
      A nationwide representative prevalence study is needed to investigate HPV
      prevalence variability among Indian regions.

PMID- 26317690
TI  - The Interpersonal-Psychological Theory of Suicide in College Student Suicide
      Screening.
AB  - Suicide screening on campus is limited by effectiveness of existing
      questionnaires. This study tests whether Interpersonal-Psychological Theory of
      Suicide (IPTS) constructs may be more effective in screening than traditional
      risk factors measures like the Interactive Screening Protocol (ISP). Participants
      were 188 traditional-age students from three different campuses recruited through
      a subject pool and peer recruiters. IPTS risk variables as a set explained all
      likelihood of higher risk responses to suicidality questions that was otherwise
      explained by risk factors, plus additional likelihood besides. Current IPTS
      measures are no screening "magic bullet," but further inquiry into use of these
      constructs is warranted. 

PMID- 26317691
TI  - HLA Class II Differentiates Between Thyroid and Polyglandular Autoimmunity.
AB  - The HLA class II genes are susceptibility genes for autoimmune endocrine
      diseases; however, scarce data are available pertaining to the determinants of
      genetic susceptibility to polyglandular autoimmunity (PGA). A total of 300
      consecutive and unselected patients with either PGA or monoglandular autoimmune
      thyroid disease (AITD) and 100 healthy control subjects were genotyped for the
      HLA class II DRB1, -DQA1, and -DQB1 alleles. Compared to patients with AITD and
      controls, the HLA-DRB1*03 (pc =0.001), *04 (pc<0.001), -DQA1*03 (pc<0.001), and 
      DQB1*02 (pc =0.001) alleles were increased in patients with PGA. When dividing
      patients with Hashimoto's thyroiditis (HT) into those with PGA (PGA-HT) vs. those
      with HT as monoglandular disease, significant differences for the DRB1*03
      (pc=0.001) and DQA1*03 (pc=0.001) alleles were observed. In contrast, the DQB1*02
      allele was more prevalent in PGA patients with Graves' disease (PGA-GD) vs. those
      with monoglandular GD (pc=0.002). The HLA-DRB1*15 (pc =0.001), -DQA1*01 (pc
      =0.001), -DQB1*05 (pc =0.002) and -DQB1*06 (pc =0.002) alleles were significantly
      less present in PGA compared to monoglandular AITD and controls, thus indicating
      protective alleles. The HLA class II alleles differentiate between mono- and
      polyglandular autoimmunity in patients with autoimmune thyroid disease. 

PMID- 26317693
TI  - Flexible Modeling of Epidemics with an Empirical Bayes Framework.
AB  - Seasonal influenza epidemics cause consistent, considerable, widespread loss
      annually in terms of economic burden, morbidity, and mortality. With access to
      accurate and reliable forecasts of a current or upcoming influenza epidemic's
      behavior, policy makers can design and implement more effective countermeasures.
      This past year, the Centers for Disease Control and Prevention hosted the
      "Predict the Influenza Season Challenge", with the task of predicting key
      epidemiological measures for the 2013-2014 U.S. influenza season with the help of
      digital surveillance data. We developed a framework for in-season forecasts of
      epidemics using a semiparametric Empirical Bayes framework, and applied it to
      predict the weekly percentage of outpatient doctors visits for influenza-like
      illness, and the season onset, duration, peak time, and peak height, with and
      without using Google Flu Trends data. Previous work on epidemic modeling has
      focused on developing mechanistic models of disease behavior and applying time
      series tools to explain historical data. However, tailoring these models to
      certain types of surveillance data can be challenging, and overly complex models
      with many parameters can compromise forecasting ability. Our approach instead
      produces possibilities for the epidemic curve of the season of interest using
      modified versions of data from previous seasons, allowing for reasonable
      variations in the timing, pace, and intensity of the seasonal epidemics, as well
      as noise in observations. Since the framework does not make strict domain
      specific assumptions, it can easily be applied to some other diseases with
      seasonal epidemics. This method produces a complete posterior distribution over
      epidemic curves, rather than, for example, solely point predictions of
      forecasting targets. We report prospective influenza-like-illness forecasts made
      for the 2013-2014 U.S. influenza season, and compare the framework's cross
      validated prediction error on historical data to that of a variety of simpler
      baseline predictors. 

PMID- 26317692
TI  - Design, Synthesis, and Cardioprotective Effects of N-Mercapto-Based Hydrogen
      Sulfide Donors.
AB  - Hydrogen sulfide (H2S) is a signaling molecule which plays regulatory roles in
      many physiological and/or pathological processes. Therefore, regulation of H2S
      levels could have great potential therapeutic value. In this work, we report the
      design, synthesis, and evaluation of a class of N-mercapto (N-SH)-based H2S
      donors. Thirty-three donors were synthesized and tested. Our results indicated
      that controllable H2S release from these donors could be achieved upon structural
      modifications. Selected donors (NSHD-1, NSHD-2, and NSHD-6) were tested in
      cellular models of oxidative damage and showed significant cytoprotective
      effects. Moreover, NSHD-1 and NSHD-2 were also found to exhibit potent protective
      effects in a murine model of myocardial ischemia reperfusion (MI/R) injury. 

PMID- 26317695
TI  - Validation and Diagnostic Efficiency of the Mini-SPIN in Spanish-Speaking
      Adolescents.
AB  - OBJECTIVES: Social Anxiety Disorder (SAD) is one of the most common mental
      disorders in adolescence. Many validated psychometric tools are available to
      diagnose individuals with SAD efficaciously. However, there is a demand for
      shortened self-report instruments that identify adolescents at risk of developing
      SAD. We validate the Mini-SPIN and its diagnostic efficiency in overcoming this
      problem in Spanish-speaking adolescents in Spain. METHODS: The psychometric
      properties of the 3-item Mini-SPIN scale for adolescents were assessed in a
      community (study 1) and clinical sample (study 2). RESULTS: Study 1 consisted of
      573 adolescents, and found the Mini-SPIN to have appropriate internal consistency
      and high construct validity. Study 2 consisted of 354 adolescents (147
      participants diagnosed with SAD and 207 healthy controls). Data revealed that the
      Mini-SPIN has good internal consistency, high construct validity and adequate
      diagnostic efficiency. CONCLUSIONS: Our findings suggest that the Mini-SPIN has
      good psychometric properties on clinical and healthy control adolescents and
      general population, which indicates that it can be used as a screening tool in
      Spanish-speaking adolescents. Cut-off scores are provided.

PMID- 26317694
TI  - Molecular Dissection of the Human Ubiquitin C Promoter Reveals Heat Shock Element
      Architectures with Activating and Repressive Functions.
AB  - The promoter of the polyubiquitin C gene (UBC) contains putative heat shock
      elements (HSEs) which are thought to mediate UBC induction upon stress. However,
      the mapping and the functional characterization of the cis-acting determinants
      for its up-regulation have not yet been addressed. In this study, the sequence
      encompassing 916 nucleotides upstream of the transcription start site of the
      human UBC gene has been dissected by in silico, in vitro and in vivo approaches.
      The information derived from this analysis was used to study the functional role
      and the interplay of the identified HSEs in mediating the transcriptional
      activation of the UBC gene under conditions of proteotoxic stress, induced by the
      proteasome inhibitor MG132. Here we demonstrate that at least three HSEs, with
      different configurations, exist in the UBC promoter: two distal, residing within
      nucleotides -841/-817 and -715/-691, and one proximal to the transcription start
      site (nt -100/-65). All of them are bound by transcription factors belonging to
      the heat shock factor (HSF) family, as determined by bandshift, supershift and
      ChIP analyses. Site-directed mutagenesis of reporter constructs demonstrated that
      while the distal elements are involved in the up-regulation of UBC in response to
      proteasome inhibition, the proximal one appears rather to function as negative
      regulator of the stress-induced transcriptional activity. This is the first
      evidence that an HSE may exert a negative role on the transcription driven by
      other HSE motifs on the same gene promoter, highlighting a new level of
      complexity in the regulation of HSFs and in the control of ubiquitin levels. 

PMID- 26317697
TI  - Modulation index for VMAT considering both mechanical and dose calculation
      uncertainties.
AB  - The aim of this study is to present a modulation index considering both
      mechanical and dose calculation uncertainties for volumetric modulated arc
      therapy (VMAT). As a modulation index considering only mechanical uncertainty of
      VMAT, MIt has been previously suggested. In this study, we developed a weighting
      factor which represents dose calculation uncertainty based on the aperture shapes
      of fluence maps at every control point of VMAT plans. In order to calculate the
      weighting factor, the thinning algorithm of image processing techniques was
      applied to measure field aperture irregularity. By combining this weighting
      factor with the previously suggested modulation index, MIt, comprehensive
      modulation index (MIc) was designed. To evaluate the performance of MIc, gamma
      passing rates, differences in mechanical parameters between plans and log files
      and differences in dose-volume parameters between plans and the plans
      reconstructed from log files were acquired with a total of 52 VMAT plans.
      Spearman's correlation coefficients (rs) between the values of MIc and measures
      of VMAT delivery accuracy were calculated. The rs values of MIc (f = 0.5) to
      global gamma passing rates with 2%/2 mm, 1%/2 mm and 2%/1 mm were  -0.728,-0.847
      and  -0.617, respectively (p  <  0.001). Those to local gamma passing rates were 
      -0.765,-0.767 and  -0.748, respectively (p  <  0.001). The rs values of MIc (f =
      0.5) to multi-leaf collimator and gantry angle errors were 0.800 and  -0.712,
      respectively (p  <  0.001). The MIc (f = 0.5) showed a total of 20 rs values (p 
      <  0.05) to the differences in dose-volumetric parameters from a total of 35
      tested cases. The MIc (f = 0.5) demonstrated considerable power to predict VMAT
      delivery accuracy showing strong correlations to various measures of VMAT
      delivery accuracy. 

PMID- 26317696
TI  - Bnip3 Binds and Activates p300: Possible Role in Cardiac Transcription and
      Myocyte Morphology.
AB  - Bnip3 is a hypoxia-regulated member of the Bcl-2 family of proteins that is
      implicated in apoptosis, programmed necrosis, autophagy and mitophagy.
      Mitochondria are thought to be the primary targets of Bnip3 although its
      activities may extend to the ER, cytoplasm, and nucleus. Bnip3 is induced in the
      heart by ischemia and pressure-overload, and may contribute to cardiomyopathy and
      heart failure. Only mitochondrial-dependent programmed death actions have been
      described for Bnip3 in the heart. Here we describe a novel activity of Bnip3 in
      cultured cardiac myocytes and transgenic mice overexpressing Bnip3 in the heart
      (Bnip3-TG). In cultured myocytes Bnip3 bound and activated the acetyltransferase
      p300, increased acetylation of histones and the transcription factor GATA4, and
      conferred p300 and GATA4-sensitive cellular morphological changes. In intact
      Bnip3-TG hearts Bnip3 also bound p300 and GATA4 and conferred enhanced GATA4
      acetylation. Bnip3-TG mice underwent age-dependent ventricular dilation and heart
      failure that was partially prevented by p300 inhibition with curcumin. The
      results suggest that Bnip3 regulates cardiac gene expression and perhaps myocyte
      morphology by activating nuclear p300 acetyltransferase activity and
      hyperacetylating histones and p300-selective transcription factors. 

PMID- 26317698
TI  - Why do orangutans leave the trees? Terrestrial behavior among wild Bornean
      orangutans (Pongo pygmaeus wurmbii) at Tuanan, Central Kalimantan.
AB  - Orangutans (genus Pongo) are the largest arboreal mammals, but Bornean orangutans
      (P. pygmaeus spp.) also spend time on the ground. Here, we investigate ground use
      among orangutans using 32,000 hr of direct focal animal observations from a well
      habituated wild population of Bornean orangutans (P. p. wurmbii) living in a
      closed-canopy swamp forest at Tuanan, Central Kalimantan, Indonesia. Ground use
      did not change with increasing observation time of well-habituated individuals,
      suggesting it was not an artifact of observer presence. Flanged males spent the
      most time on the ground (ca. 5% of active time), weaned immatures the least
      (around 1%). Females and immatures descended mainly to feed, especially on
      termites, whereas flanged males traveled more while on the ground. Flanged males
      may travel more inconspicuously, and perhaps also faster, when moving on the
      ground. In addition, orangutans engaged in ground-specific behavior, including
      drinking from and bathing in swamp pools. Supplementary records from 20 ground
      level camera traps, totaling 3986 trap days, confirmed the observed age-sex
      biases in ground use at Tuanan. We conclude that ground use is a natural part of
      the Bornean orangutan behavioral repertoire, however it remains unclear to what
      extent food scarcity and canopy structure explain population differences in
      ground use.

PMID- 26317700
TI  - Non-Markovianity of Gaussian Channels.
AB  - We introduce a necessary and sufficient criterion for the non-Markovianity of
      Gaussian quantum dynamical maps based on the violation of divisibility. The
      criterion is derived by defining a general vectorial representation of the
      covariance matrix which is then exploited to determine the condition for the
      complete positivity of partial maps associated with arbitrary time intervals.
      Such construction does not rely on the Choi-Jamiolkowski representation and does
      not require optimization over states. 

PMID- 26317699
TI  - Transcriptome Analysis of the Preterm Rabbit Lung after Seven Days of Hyperoxic
      Exposure.
AB  - The neonatal management of preterm born infants often results in damage to the
      developing lung and subsequent morbidity, referred to as bronchopulmonary
      dysplasia (BPD). Animal models may help in understanding the molecular processes
      involved in this condition and define therapeutic targets. Our goal was to
      identify molecular pathways using the earlier described preterm rabbit model of
      hyperoxia induced lung-injury. Transcriptome analysis by mRNA-sequencing was
      performed on lungs from preterm rabbit pups born at day 28 of gestation (term: 31
      days) and kept in hyperoxia (95% O2) for 7 days. Controls were preterm pups kept
      in normoxia. Transcriptomic data were analyzed using Array Studio and Ingenuity
      Pathway Analysis (IPA), in order to identify the central molecules responsible
      for the observed transcriptional changes. We detected 2217 significantly
      dysregulated transcripts following hyperoxia, of which 90% could be identified.
      Major pathophysiological dysregulations were found in inflammation, lung
      development, vascular development and reactive oxygen species (ROS) metabolism.
      To conclude, amongst the many dysregulated transcripts, major changes were found
      in the inflammatory, oxidative stress and lung developmental pathways. This
      information may be used for the generation of new treatment hypotheses for
      hyperoxia-induced lung injury and BPD. 

PMID- 26317701
TI  - Estimating Outcome Probabilities of Quantum Circuits Using Quasiprobabilities.
AB  - We present a method for estimating the probabilities of outcomes of a quantum
      circuit using Monte Carlo sampling techniques applied to a quasiprobability
      representation. Our estimate converges to the true quantum probability at a rate
      determined by the total negativity in the circuit, using a measure of negativity
      based on the 1-norm of the quasiprobability. If the negativity grows at most
      polynomially in the size of the circuit, our estimator converges efficiently.
      These results highlight the role of negativity as a measure of nonclassical
      resources in quantum computation.

PMID- 26317702
TI  - Quantum Storage of Three-Dimensional Orbital-Angular-Momentum Entanglement in a
      Crystal.
AB  - Here we present the quantum storage of three-dimensional orbital-angular-momentum
      photonic entanglement in a rare-earth-ion-doped crystal. The properties of the
      entanglement and the storage process are confirmed by the violation of the Bell
      type inequality generalized to three dimensions after storage (S=2.152+/-0.033).
      The fidelity of the memory process is 0.993+/-0.002, as determined through
      complete quantum process tomography in three dimensions. An assessment of the
      visibility of the stored weak coherent pulses in higher-dimensional spaces
      demonstrates that the memory is highly reliable for 51 spatial modes. These
      results pave the way towards the construction of high-dimensional and multiplexed
      quantum repeaters based on solid-state devices. The multimode capacity of rare
      earth-based optical processors goes beyond the temporal and the spectral degree
      of freedom, which might provide a useful tool for photonic information
      processing. 

PMID- 26317703
TI  - Reversible Framework for Quantum Resource Theories.
AB  - In recent years it has been recognized that properties of physical systems such
      as entanglement, athermality, and asymmetry, can be viewed as resources for
      important tasks in quantum information, thermodynamics, and other areas of
      physics. This recognition was followed by the development of specific quantum
      resource theories (QRTs), such as entanglement theory, determining how quantum
      states that cannot be prepared under certain restrictions may be manipulated and
      used to circumvent the restrictions. Here we discuss the general structure of
      QRTs, and show that under a few assumptions (such as convexity of the set of free
      states), a QRT is asymptotically reversible if its set of allowed operations is
      maximal, that is, if the allowed operations are the set of all operations that do
      not generate (asymptotically) a resource. In this case, the asymptotic conversion
      rate is given in terms of the regularized relative entropy of a resource which is
      the unique measure or quantifier of the resource in the asymptotic limit of many
      copies of the state. This measure also equals the smoothed version of the
      logarithmic robustness of the resource. 

PMID- 26317704
TI  - Variationally Optimized Free-Energy Flooding for Rate Calculation.
AB  - We propose a new method to obtain kinetic properties of infrequent events from
      molecular dynamics simulation. The procedure employs a recently introduced
      variational approach [Valsson and Parrinello, Phys. Rev. Lett. 113, 090601
      (2014)] to construct a bias potential as a function of several collective
      variables that is designed to flood the associated free energy surface up to a
      predefined level. The resulting bias potential effectively accelerates
      transitions between metastable free energy minima while ensuring bias-free
      transition states, thus allowing accurate kinetic rates to be obtained. We test
      the method on a few illustrative systems for which we obtain an order of
      magnitude improvement in efficiency relative to previous approaches and several
      orders of magnitude relative to unbiased molecular dynamics. We expect an even
      larger improvement in more complex systems. This and the ability of the
      variational approach to deal efficiently with a large number of collective
      variables will greatly enhance the scope of these calculations. This work is a
      vindication of the potential that the variational principle has if applied in
      innovative ways. 

PMID- 26317705
TI  - Maximizing Coherence of Oscillations by External Locking.
AB  - We study how coherence of noisy oscillations can be optimally enhanced by
      external locking. Based on the condition of minimizing the phase diffusion
      constant, we find the optimal forcing explicitly in the limits of small and large
      noise, in dependence of the phase sensitivity of the oscillator. We show
      analytically that the form of the optimal force bifurcates with the noise
      intensity; this is confirmed by the analysis of an optimal locking forcing for an
      experimentally obtained phase sensitivity of a neural cell. In the limit of small
      noise, the results are compared with purely deterministic conditions of optimal
      locking. 

PMID- 26317706
TI  - Testing the Dark Matter Scenario for PeV Neutrinos Observed in IceCube.
AB  - Late time decay of very heavy dark matter is considered as one of the possible
      explanations for diffuse PeV neutrinos observed in IceCube. We consider
      implications of multimessenger constraints, and show that proposed models are
      marginally consistent with the diffuse gamma-ray background data. Critical tests
      are possible by a detailed analysis and identification of the sub-TeV isotropic
      diffuse gamma-ray data observed by Fermi and future observations of sub-PeV gamma
      rays by observatories like HAWC or Tibet AS+MD. In addition, with several-year
      observations by next-generation telescopes such as IceCube-Gen2, muon neutrino
      searches for nearby dark matter halos such as the Virgo cluster should allow us
      to rule out or support the dark matter models, independently of gamma-ray and
      anisotropy tests. 

PMID- 26317707
TI  - Four-Dimensional Entropy from Three-Dimensional Gravity.
AB  - At the horizon of a black hole, the action of (3+1)-dimensional loop quantum
      gravity acquires a boundary term that is formally identical to an action for
      three-dimensional gravity. I show how to use this correspondence to obtain the
      entropy of the (3+1)-dimensional black hole from well-understood conformal field
      theory computations of the entropy in (2+1)-dimensional de Sitter space. 

PMID- 26317708
TI  - Gravity and the Stability of the Higgs Vacuum.
AB  - We discuss the effect of gravitational interactions on the lifetime of the Higgs
      vacuum where generic quantum gravity corrections are taken into account. Using a
      "thin-wall" approximation, we provide a proof of principle that small black holes
      can act as seeds for vacuum decay, spontaneously nucleating a new Higgs phase
      centered on the black hole with a lifetime measured in millions of Planck times
      rather than billions of years. The corresponding parameter space constraints are,
      however, extremely stringent; therefore, we also present numerical evidence
      suggesting that with thick walls, the parameter space may open up. Implications
      for collider black holes are discussed. 

PMID- 26317709
TI  - Constraints on Dark Matter Interactions with Standard Model Particles from Cosmic
      Microwave Background Spectral Distortions.
AB  - We propose a new method to constrain elastic scattering between dark matter (DM)
      and standard model particles in the early Universe. Direct or indirect thermal
      coupling of nonrelativistic DM with photons leads to a heat sink for the latter.
      This results in spectral distortions of the cosmic microwave background (CMB),
      the amplitude of which can be as large as a few times the DM-to-photon-number
      ratio. We compute CMB spectral distortions due to DM-proton, DM-electron, and DM
      photon scattering for generic energy-dependent cross sections and DM mass
      m_{chi}?1 keV. Using Far-Infrared Absolute Spectrophotometer measurements, we set
      constraints on the cross sections for m_{chi}?0.1 MeV. In particular, for energy
      independent scattering we obtain sigma_{DM-proton}?10^{-24} cm^{2}
      (keV/m_{chi})^{1/2}, sigma_{DM-electron}?10^{-27} cm^{2} (keV/m_{chi})^{1/2}, and
      sigma_{DM-photon}?10^{-39} cm^{2} (m_{chi}/keV). An experiment with the
      characteristics of the Primordial Inflation Explorer would extend the regime of
      sensitivity up to masses m_{chi}~1 GeV.

PMID- 26317710
TI  - Constraining de Sitter Space in String Theory.
AB  - We argue that the heterotic string does not have classical vacua corresponding to
      de Sitter space-times of dimension four or higher. The same conclusion applies to
      type II vacua in the absence of Ramond-Ramond fluxes. Our argument extends prior
      supergravity no-go results to regimes of high curvature. We discuss the
      interpretation of the heterotic result from the perspective of dual type II
      orientifold constructions. Our result suggests that the genericity arguments used
      in string landscape discussions should be viewed with caution. 

PMID- 26317711
TI  - Effective Dark Matter Halo Catalog in f(R) Gravity.
AB  - We introduce the idea of an effective dark matter halo catalog in f(R) gravity,
      which is built using the effective density field. Using a suite of high
      resolution N-body simulations, we find that the dynamical properties of halos,
      such as the distribution of density, velocity dispersion, specific angular
      momentum and spin, in the effective catalog of f(R) gravity closely mimic those
      in the cold dark matter model with a cosmological constant (LambdaCDM). Thus,
      when using effective halos, an f(R) model can be viewed as a LambdaCDM model.
      This effective catalog therefore provides a convenient way for studying the
      baryonic physics, the galaxy halo occupation distribution and even semianalytical
      galaxy formation in f(R) cosmologies. 

PMID- 26317712
TI  - Nonrenormalization Theorems without Supersymmetry.
AB  - We derive a new class of one-loop nonrenormalization theorems that strongly
      constrain the running of higher dimension operators in a general four-dimensional
      quantum field theory. Our logic follows from unitarity: cuts of one-loop
      amplitudes are products of tree amplitudes, so if the latter vanish then so too
      will the associated divergences. Finiteness is then ensured by simple selection
      rules that zero out tree amplitudes for certain helicity configurations. For each
      operator we define holomorphic and antiholomorphic weights, (w,w[over -])=(n
      h,n+h), where n and h are the number and sum over helicities of the particles
      created by that operator. We argue that an operator O_{i} can only be
      renormalized by an operator O_{j} if w_{i}>=w_{j} and w[over -]_{i}>=w[over 
      ]_{j}, absent nonholomorphic Yukawa couplings. These results explain and
      generalize the surprising cancellations discovered in the renormalization of
      dimension six operators in the standard model. Since our claims rely on unitarity
      and helicity rather than an explicit symmetry, they apply quite generally. 

PMID- 26317713
TI  - Improved Measurement of the pi->enu Branching Ratio.
AB  - A new measurement of the branching ratio R_{e/MU}=Gamma(pi^{+}->e^{+}nu+pi^{+}
      >e^{+}nugamma)/Gamma(pi^{+}->MU^{+}nu+pi^{+}->MU^{+}nugamma) resulted in
      R_{e/MU}^{exp}=[1.2344+/-0.0023(stat)+/-0.0019(syst)]*10^{-4}. This is in
      agreement with the standard model prediction and improves the test of electron
      muon universality to the level of 0.1%. 

PMID- 26317715
TI  - Hydrodynamics Beyond the Gradient Expansion: Resurgence and Resummation.
AB  - Consistent formulations of relativistic viscous hydrodynamics involve short-lived
      modes, leading to asymptotic rather than convergent gradient expansions. In this
      Letter we consider the Muller-Israel-Stewart theory applied to a longitudinally
      expanding quark-gluon plasma system and identify hydrodynamics as a universal
      attractor without invoking the gradient expansion. We give strong evidence for
      the existence of this attractor and then show that it can be recovered from the
      divergent gradient expansion by Borel summation. This requires careful accounting
      for the short-lived modes which leads to an intricate mathematical structure
      known from the theory of resurgence. 

PMID- 26317716
TI  - Coupled-Trajectory Quantum-Classical Approach to Electronic Decoherence in
      Nonadiabatic Processes.
AB  - We present a novel quantum-classical approach to nonadiabatic dynamics, deduced
      from the coupled electronic and nuclear equations in the framework of the exact
      factorization of the electron-nuclear wave function. The method is based on the
      quasiclassical interpretation of the nuclear wave function, whose phase is
      related to the classical momentum and whose density is represented in terms of
      classical trajectories. In this approximation, electronic decoherence is
      naturally induced as an effect of the coupling to the nuclei and correctly
      reproduces the expected quantum behavior. Moreover, the splitting of the nuclear
      wave packet is captured as a consequence of the correct approximation of the time
      dependent potential of the theory. This new approach offers a clear improvement
      over Ehrenfest-like dynamics. The theoretical derivation presented in this Letter
      is supported by numerical results that are compared to quantum mechanical
      calculations. 

PMID- 26317717
TI  - Creating State-Dependent Lattices for Ultracold Fermions by Magnetic Gradient
      Modulation.
AB  - We demonstrate a versatile method for creating state-dependent optical lattices
      by applying a magnetic field gradient modulated in time. This allows for tuning
      the relative amplitude and sign of the tunneling for different internal states.
      We observe substantially different momentum distributions depending on the spin
      state of fermionic ^{40}K atoms. Using dipole oscillations, we probe the spin
      dependent band structure and find good agreement with theory. In situ expansion
      dynamics demonstrate that one state can be completely localized while others
      remain itinerant. A systematic study shows negligible heating and lifetimes of
      several seconds in the Hubbard regime.

PMID- 26317718
TI  - Rapid Production of Uniformly Filled Arrays of Neutral Atoms.
AB  - We demonstrate rapid loading of a small array of optical tweezers with a single
      ^{87}Rb atom per site. We find that loading efficiencies of up to 90% per tweezer
      are achievable in less than 170 ms for traps separated by more than 1.7 MUm.
      Interestingly, we find the load efficiency is affected by nearby traps and
      present the efficiency as a function of the spacing between two optical tweezers.
      This enhanced loading, combined with subsequent rearranging of filled sites, will
      enable the study of quantum many-body systems via quantum gas assembly.

PMID- 26317719
TI  - Interferometric Laser Cooling of Atomic Rubidium.
AB  - We report the 1D cooling of ^{85}Rb atoms using a velocity-dependent optical
      force based upon Ramsey matter-wave interferometry. Using stimulated Raman
      transitions between ground hyperfine states, 12 cycles of the interferometer
      sequence cool a freely moving atom cloud from 21 to 3 MUK. This pulsed analog of
      continuous-wave Doppler cooling is effective at temperatures down to the recoil
      limit; with augmentation pulses to increase the interferometer area, it should
      cool more quickly than conventional methods and be more suitable for species that
      lack a closed radiative transition.

PMID- 26317720
TI  - Theory of Long-Range Ultracold Atom-Molecule Photoassociation.
AB  - The creation of ultracold molecules is currently limited to diatomic species. In
      this Letter, we present a theoretical description of the photoassociation of
      ultracold atoms and molecules to create ultracold excited triatomic molecules,
      thus being a novel example of a light-assisted ultracold chemical reaction. The
      calculation of the photoassociation rate of an ultracold Cs_{2} molecule in its
      rovibrational ground state with an ultracold Cs atom at frequencies close to its
      resonant excitation is reported, based on the solution of the quantum dynamics
      involving the atom-molecule long-range interactions and assuming a model
      potential for the short-range physics. The rate for the formation of excited
      Cs_{3} molecules is predicted to be comparable with currently observed atom-atom
      photoassociation rates. We formulate an experimental proposal to observe this
      process relying on the available techniques of optical lattices and standard
      photoassociation spectroscopy. 

PMID- 26317721
TI  - Gaussian Process Model for Collision Dynamics of Complex Molecules.
AB  - We show that a Gaussian process model can be combined with a small number (of
      order 100) of scattering calculations to provide a multidimensional dependence of
      scattering observables on the experimentally controllable parameters (such as the
      collision energy or temperature) as well as the potential energy surface (PES)
      parameters. For the case of Ar-C_{6}H_{6} collisions, we show that 200 classical
      trajectory calculations are sufficient to provide a ten-dimensional hypersurface,
      giving the dependence of the collision lifetimes on the collision energy,
      internal temperature, and eight PES parameters. This can be used for solving the
      inverse scattering problem, for the efficient calculation of thermally averaged
      observables, for reducing the error of the molecular dynamics calculations by
      averaging over the PES variations, and for the analysis of the sensitivity of the
      observables to individual parameters determining the PES. Trained by a
      combination of classical and quantum calculations, the model provides an accurate
      description of the quantum scattering cross sections, even near scattering
      resonances.

PMID- 26317722
TI  - Light with Tunable Non-Markovian Phase Imprint.
AB  - We introduce a simple and flexible method to generate spatially non-Markovian
      light with tunable coherence properties in one and two dimensions. The unusual
      behavior of this light is demonstrated experimentally by probing the far field
      and by recording its diffraction pattern after a double slit: In both cases we
      observe, instead of a central intensity maximum, a line- or cross-shaped dark
      region, whose width and profile depend on the non-Markovian coherence properties.
      Because these properties can be controlled and easily reproduced in experiment,
      the presented approach lends itself to serving as a test bed to study and gain a
      deeper understanding of non-Markovian processes. 

PMID- 26317723
TI  - Influence of Gas Turbulence on the Instability of an Air-Water Mixing Layer.
AB  - We present the first evidence of the direct influence of gas turbulence on the
      shear instability of a planar air-water mixing layer. We show with two different
      experiments that increasing the level of velocity fluctuations in the gas phase
      continuously increases the frequency of the instability, up to a doubling of
      frequency for the largest turbulence intensity investigated. A modified
      spatiotemporal stability analysis taking turbulence into account via a simple
      Reynolds stress closure provides the right trend and magnitude for this effect. 

PMID- 26317724
TI  - Self-Propelled Droplet Removal from Hydrophobic Fiber-Based Coalescers.
AB  - Fiber-based coalescers are widely used to accumulate droplets from aerosols and
      emulsions, where the accumulated droplets are typically removed by gravity or
      shear. This Letter reports self-propelled removal of drops from a hydrophobic
      fiber, where the surface energy released upon drop coalescence overcomes the drop
      fiber adhesion, producing spontaneous departure that would not occur on a flat
      substrate of the same contact angle. The self-removal takes place above a
      threshold drop-to-fiber radius ratio, and the departure speed is close to the
      capillary-inertial velocity at large radius ratios. 

PMID- 26317725
TI  - Ladder Climbing and Autoresonant Acceleration of Plasma Waves.
AB  - When the background density in a bounded plasma is modulated in time, discrete
      modes become coupled. Interestingly, for appropriately chosen modulations, the
      average plasmon energy might be made to grow in a ladderlike manner, achieving
      upconversion or downconversion of the plasmon energy. This reversible process is
      identified as a classical analog of the effect known as quantum ladder climbing,
      so that the efficiency and the rate of this process can be written immediately by
      analogy to a quantum particle in a box. In the limit of a densely spaced
      spectrum, ladder climbing transforms into continuous autoresonance; plasmons may
      then be manipulated by chirped background modulations much like electrons are
      autoresonantly manipulated by chirped fields. By formulating the wave dynamics
      within a universal Lagrangian framework, similar ladder climbing and
      autoresonance effects are predicted to be achievable with general linear waves in
      both plasma and other media. 

PMID- 26317726
TI  - Effective Hamiltonians for Rapidly Driven Many-Body Lattice Systems: Induced
      Exchange Interactions and Density-Dependent Hoppings.
AB  - We consider 1D lattices described by Hubbard or Bose-Hubbard models, in the
      presence of periodic high-frequency perturbations, such as uniform ac force or
      modulation of hopping coefficients. Effective Hamiltonians for interacting
      particles are derived using an averaging method resembling classical canonical
      perturbation theory. As is known, a high-frequency force may renormalize hopping
      coefficients, causing interesting phenomena such as coherent destruction of
      tunneling and creation of artificial gauge fields. We find explicitly additional
      corrections to the effective Hamiltonians due to interactions, corresponding to
      nontrivial processes such as single-particle density-dependent tunneling,
      correlated pair hoppings, nearest neighbor interactions, etc. Some of these
      processes arise also in multiband lattice models, and are capable of giving rise
      to a rich variety of quantum phases. The apparent contradiction with other
      methods, e.g., Floquet-Magnus expansion, is explained. The results may be useful
      for designing effective Hamiltonian models in experiments with ultracold atoms,
      as well as in the field of ultrafast nonequilibrium magnetism. An example of
      manipulating exchange interaction in a Mott-Hubbard insulator is considered,
      where our corrections play an essential role. 

PMID- 26317727
TI  - Longitudinal Spin Diffusion in a Nondegenerate Trapped ^{87}Rb Gas.
AB  - Longitudinal spin diffusion of two pseudospin domains is studied in a trapped
      ^{87}Rb sample above quantum degeneracy, and the effect of coherence in the
      domain wall on the dynamics of the system is investigated. Coherence in a domain
      wall leads to transverse-spin-mediated longitudinal spin diffusion that is slower
      than classical predictions, as well as altering the domains' oscillation
      frequency. The system also shows an instability in the longitudinal spin dynamics
      as longitudinal and transverse spin components couple, and a conversion of
      longitudinal spin to transverse spin is observed, resulting in an increase in the
      total amount of coherence in the system. 

PMID- 26317728
TI  - Stable Dilute Supersolid of Two-Dimensional Dipolar Bosons.
AB  - We consider two-dimensional bosonic dipoles oriented perpendicularly to the
      plane. On top of the usual two-body contact and long-range dipolar interactions
      we add a contact three-body repulsion as expected, in particular, for dipoles in
      the bilayer geometry with tunneling. The three-body repulsion is crucial for
      stabilizing the system, and we show that our model allows for stable continuous
      space supersolid states in the dilute regime and calculate the zero-temperature
      phase diagram. 

PMID- 26317729
TI  - Experimental Observation of Quasicrystal Growth.
AB  - The growth of an Al-Ni-Co decagonal quasicrystal was observed by in situ, high
      temperature, high-resolution transmission electron microscopy. The tiling
      patterns extracted from a series of high-resolution transmission electron
      microscopy images were analyzed on the basis of the high-dimensional description
      of quasicrystalline structures. The analyses indicated that the growth proceeded
      with frequent error-and-repair processes. The final, grown structure showed
      nearly perfect quasicrystalline order. Our observations suggest that the repair
      process by phason relaxation, rather than local growth rule, plays an essential
      role in the construction of ideal quasicrystalline order in real materials.

PMID- 26317730
TI  - X-Ray Diffraction of Solid Tin to 1.2 TPa.
AB  - We report direct in situ measurements of the crystal structure of tin between
      0.12 and 1.2 TPa, the highest stress at which a crystal structure has ever been
      observed. Using angle-dispersive powder x-ray diffraction, we find that
      dynamically compressed Sn transforms to the body-centered-cubic (bcc) structure
      previously identified by ambient-temperature quasistatic-compression studies and
      by zero-kelvin density-functional theory predictions between 0.06 and 0.16 TPa.
      However, we observe no evidence for the hexagonal close-packed (hcp) phase found
      by those studies to be stable above 0.16 TPa. Instead, our results are consistent
      with bcc up to 1.2 TPa. We conjecture that at high temperature bcc is stabilized
      relative to hcp due to differences in vibrational free energy.

PMID- 26317731
TI  - Stability of a Screw Dislocation in a ?011? Copper Nanowire.
AB  - The stability of a screw dislocation in a free ?011? copper nanowire is
      investigated using atomistic calculations. This study reveals a strong anisotropy
      of the Eshelby potential well (EPW) that traps the dislocation. Moreover the
      depth of the EPW is found to vanish when the radius of the nanowire decreases. It
      is demonstrated that this behavior is due to the dissociated state of the
      dislocation. 

PMID- 26317732
TI  - Emergence of an Out-of-Plane Optical Phonon (ZO) Kohn Anomaly in
      Quasifreestanding Epitaxial Graphene.
AB  - In neutral graphene, two prominent cusps known as Kohn anomalies are found in the
      phonon dispersion of the highest optical phonon at q=Gamma (LO branch) and q=K
      (TO branch), reflecting a significant electron-phonon coupling (EPC) to undoped
      Dirac electrons. In this work, high-resolution electron energy loss spectroscopy
      is used to measure the phonon dispersion around the Gamma point in
      quasifreestanding graphene epitaxially grown on Pt(111). The Kohn anomaly for the
      LO phonon is observed at finite momentum q~2k_{F} from Gamma, with a shape in
      excellent agreement with the theory and consistent with known values of the EPC
      and the Fermi level. More strikingly, we also observe a Kohn anomaly at the same
      momentum for the out-of-plane optical phonon (ZO) branch. This observation is the
      first direct evidence of the coupling of the ZO mode with Dirac electrons, which
      is forbidden for freestanding graphene but becomes allowed in the presence of a
      substrate. Moreover, we estimate the EPC to be even greater than that of the LO
      mode, making graphene on Pt(111) an optimal system to explore the effects of this
      new coupling in the electronic properties.

PMID- 26317733
TI  - Probing Charges on the Atomic Scale by Means of Atomic Force Microscopy.
AB  - Kelvin probe force spectroscopy was used to characterize the charge distribution
      of individual molecules with polar bonds. Whereas this technique represents the
      charge distribution with moderate resolution for large tip-molecule separations,
      it fails for short distances. Here, we introduce a novel local force spectroscopy
      technique which allows one to better disentangle electrostatic from other
      contributions in the force signal. It enables one to obtain charge-related maps
      at even closer tip-sample distances, where the lateral resolution is further
      enhanced. This enhanced resolution allows one to resolve contrast variations
      along individual polar bonds. 

PMID- 26317734
TI  - Analytic Flow Equations for the Fermi Liquid Parameters of the Anderson Impurity
      Model.
AB  - The low temperature behavior of a Fermi liquid can be described in terms of
      quasiparticle excitations that are in 1-1 correspondence with those of the
      noninteracting system. Because of adiabatic continuity, the Landau parameters,
      which describe the interactions between the quasiparticles, must evolve
      continuously as the interactions are turned on and be described by a set of flow
      equations. For strongly correlated electron systems it is not possible to follow
      this flow in perturbation theory when the interactions become strong. We explore
      the idea here of overcoming this problem by renormalizing the quasiparticles in
      this flow using a renormalized perturbation theory. This approach is tested in
      the case of a single impurity Anderson model. Analytic flow equations are derived
      which give excellent results for the Landau parameters in the strong correlation
      regime. 

PMID- 26317735
TI  - Collective Modes and Structural Modulation in Ni-Mn-Ga(Co) Martensite Thin Films
      Probed by Femtosecond Spectroscopy and Scanning Tunneling Microscopy.
AB  - The origin of the martensitic transition in the magnetic shape memory alloy Ni-Mn
      Ga has been widely discussed. While several studies suggest it is electronically
      driven, the adaptive martensite model reproduced the peculiar nonharmonic lattice
      modulation. We used femtosecond spectroscopy to probe the temperature and doping
      dependence of collective modes, and scanning tunneling microscopy revealed the
      corresponding static modulations. We show that the martensitic phase can be
      described by a complex charge-density wave tuned by magnetic ordering and strong
      electron-lattice coupling. 

PMID- 26317736
TI  - Anderson Localization and the Quantum Phase Diagram of Three Dimensional
      Disordered Dirac Semimetals.
AB  - We study the quantum phase diagram of a three dimensional noninteracting Dirac
      semimetal in the presence of either quenched axial or scalar potential disorder,
      by calculating the average and the typical density of states as well as the
      inverse participation ratio using numerically exact methods. We show that as a
      function of the disorder strength a half-filled (i.e., undoped) Dirac semimetal
      displays three distinct ground states, namely an incompressible semimetal, a
      compressible diffusive metal, and a localized Anderson insulator, in stark
      contrast to a conventional dirty metal that only supports the latter two phases.
      We establish the existence of two distinct quantum critical points, which
      respectively govern the semimetal-metal and the metal-insulator quantum phase
      transitions and also reveal their underlying multifractal nature. Away from half
      filling the (doped) system behaves as a diffusive metal that can undergo Anderson
      localization only, which is shown by determining the mobility edge and the phase
      diagram in terms of energy and disorder. 

PMID- 26317737
TI  - Spin Hall Effects Due to Phonon Skew Scattering.
AB  - A diversity of spin Hall effects in metallic systems is known to rely on Mott
      skew scattering. In this work its high-temperature counterpart, phonon skew
      scattering, which is expected to be of foremost experimental relevance, is
      investigated. In particular, the phonon skew scattering spin Hall conductivity is
      found to be practically T independent for temperatures above the Debye
      temperature T_{D}. As a consequence, in Rashba-like systems a high-T linear
      behavior of the spin Hall angle demonstrates the dominance of extrinsic spin
      orbit scattering only if the intrinsic spin splitting is smaller than the
      temperature. 

PMID- 26317738
TI  - Origin of the Anomalous Mass Renormalization in Metallic Quantum Well States of
      Strongly Correlated Oxide SrVO_{3}.
AB  - In situ angle-resolved photoemission spectroscopy (ARPES) has been performed on
      SrVO_{3} ultrathin films, which show metallic quantum well (QW) states, to unveil
      the origin of the anomalous mass enhancement in the QW subbands. The line-shape
      analysis of the ARPES spectra reveals that the strength of the electron
      correlation increases as the subband bottom energy approaches the Fermi level.
      These results indicate that the anomalous subband-dependent mass enhancement
      mainly arises from the quasi-one-dimensional character of confined V 3d states as
      a result of their orbital-selective quantization.

PMID- 26317739
TI  - Helical Spin Order from Topological Dirac and Weyl Semimetals.
AB  - We study dynamical mass generation and the resultant helical spin orders in
      topological Dirac and Weyl semimetals, including the edge states of quantum spin
      Hall insulators, the surface states of weak topological insulators, and the bulk
      materials of Weyl semimetals. In particular, the helical spin textures of Weyl
      semimetals manifest the spin-momentum locking of Weyl fermions in a visible
      manner. The spin-wave fluctuations of the helical order carry electric charge
      density; therefore, the spin textures can be electrically controlled in a simple
      and predictable manner. 

PMID- 26317740
TI  - Reconfigurable Quantum-Dot Molecules Created by Atom Manipulation.
AB  - Quantum-dot molecules were constructed on a semiconductor surface using atom
      manipulation by scanning tunneling microscopy (STM) at 5 K. The molecules consist
      of several coupled quantum dots, each of which comprises a chain of charged
      adatoms that electrostatically confines intrinsic surface-state electrons. The
      coupling takes place across tunnel barriers created reversibly using the STM tip.
      These barriers have an invariant, reproducible atomic structure and can be
      positioned-and repeatedly repositioned-to create a series of reconfigurable
      quantum-dot molecules with atomic precision.

PMID- 26317741
TI  - Quantum Spin Liquid Emerging from Antiferromagnetic Order by Introducing
      Disorder.
AB  - Quantum spin liquids, which are spin versions of quantum matter, have been sought
      after in systems with geometrical frustration. We show that disorder drives a
      classical magnet into a quantum spin liquid through conducting NMR experiments on
      an organic Mott insulator, kappa-(ET)_{2}Cu[N(CN)_{2}]Cl. Antiferromagnetic
      ordering in the pristine crystal, when irradiated by x rays, disappears. Spin
      freezing, spin gap, and critical slowing down are not observed, but gapless spin
      excitations emerge, suggesting a novel role of disorder that brings forth a
      quantum spin liquid from a classical ordered state. 

PMID- 26317742
TI  - Candidate Source of Flux Noise in SQUIDs: Adsorbed Oxygen Molecules.
AB  - A major obstacle to using superconducting quantum interference devices (SQUIDs)
      as qubits is flux noise. We propose that the heretofore mysterious spins
      producing flux noise could be O_{2} molecules adsorbed on the surface. Using
      density functional theory calculations, we find that an O_{2} molecule adsorbed
      on an alpha-alumina surface has a magnetic moment of ~1.8 MU_{B}. The spin is
      oriented perpendicular to the axis of the O-O bond, the barrier to spin rotations
      is about 10 mK. Monte Carlo simulations of ferromagnetically coupled, anisotropic
      XY spins on a square lattice find 1/f magnetization noise, consistent with flux
      noise in Al SQUIDs.

PMID- 26317743
TI  - Efficient Cluster Algorithm for Spin Glasses in Any Space Dimension.
AB  - Spin systems with frustration and disorder are notoriously difficult to study,
      both analytically and numerically. While the simulation of ferromagnetic
      statistical mechanical models benefits greatly from cluster algorithms, these
      accelerated dynamics methods remain elusive for generic spin-glass-like systems.
      Here, we present a cluster algorithm for Ising spin glasses that works in any
      space dimension and speeds up thermalization by at least one order of magnitude
      at temperatures where thermalization is typically difficult. Our isoenergetic
      cluster moves are based on the Houdayer cluster algorithm for two-dimensional
      spin glasses and lead to a speedup over conventional state-of-the-art methods
      that increases with the system size. We illustrate the benefits of the
      isoenergetic cluster moves in two and three space dimensions, as well as the
      nonplanar chimera topology found in the D-Wave Inc. quantum annealing machine. 

PMID- 26317744
TI  - Numerical Evidence of Quantum Melting of Spin Ice: Quantum-to-Classical
      Crossover.
AB  - Unbiased quantum Monte Carlo simulations are performed on the nearest-neighbor
      spin-1/2 pyrochlore XXZ model with an antiferromagnetic longitudinal and the weak
      ferromagnetic transverse exchange couplings, J and J_{?}. The specific heat
      exhibits a broad peak at T_{CSI}~0.2J associated with a crossover to a classical
      Coulomb liquid regime showing a suppressed spin-ice monopole density, a broadened
      pinch-point singularity, and the Pauling entropy for |J_{?}|?J, as in classical
      spin ice. On further cooling, the entropy restarts decaying for J_{?}>J_{?c}~
      0.104J, producing another broad specific heat peak for a crossover to a bosonic
      quantum Coulomb liquid, where the spin correlation contains both photon and
      quantum spin-ice monopole contributions. With negatively increasing J_{?} across
      J_{?c}, a first-order thermal phase transition occurs from the quantum Coulomb
      liquid to an XY ferromagnet. Relevance to magnetic rare-earth pyrochlore oxides
      is discussed.

PMID- 26317745
TI  - Controlled Strong Coupling and Absence of Dark Polaritons in Microcavities with
      Double Quantum Wells.
AB  - We demonstrate an efficient switching between strong and weak exciton-photon
      coupling regimes in microcavity-embedded asymmetric double quantum wells,
      controlled by an applied electric field. We show that a fine-tuning of the
      electric field leads to drastic changes in the polariton properties, with the
      polariton ground state being redshifted by a few meV and having acquired
      prominent features of a spatially indirect dipolar exciton. We study the
      properties of dipolar exciton polaritons, called dipolaritons, on a microscopic
      level and show that, unlike recent findings, they are not dark polaritons but,
      owing to the finite size of the exciton, are mixed states with a comparable
      contribution of the cavity photon, bright direct, and long-living indirect
      exciton modes. 

PMID- 26317746
TI  - Confinement Induced Plastic Crystal-to-Crystal Transitions in Rodlike Particles
      with Long-Ranged Repulsion.
AB  - Colloidal particles in geometrical confinement display a complex variety of
      packing structures different from their three-dimensional (3D) bulk counterpart.
      Here, we confined charged rodlike colloids with long-ranged repulsions to a thin
      wedge-shaped cell and show, by quantitative 3D confocal microscopy, that not only
      their positional but also their orientational order depends sensitively upon the
      slit width. Synchronized with transitions in lattice symmetry and number of
      layers confinement induces plastic crystal-to-crystal transitions. A model
      analysis suggests that this complex sequence of more or less rotationally ordered
      states originates from the subtle competition between the electrostatic repulsion
      of a rod with the wall and with its neighbors. 

PMID- 26317747
TI  - Linear and Nonlinear Universality in the Rheology of Polymer Melts and Solutions.
AB  - Understanding the dynamics of polymeric liquids has great importance in the
      design and processing of soft materials. While slow flow dynamics is now
      resolved, fast flow dynamics is still unsolved, especially due to the lack of
      experimental evidence. We here manipulate a poly(methyl methacrylate) solution
      into exhibiting the same flow behavior as a polystyrene melt. Strikingly similar
      responses of the fluids are seen both in slow and very fast flow. With this
      discovery we show that dynamics in polymeric liquids can be generalized and
      captured in one single polymer physics model. 

PMID- 26317748
TI  - Decreased Interfacial Tension of Demixed Aqueous Polymer Solutions due to Charge.
AB  - Electric charge at the water-water interface of demixed solutions of neutral
      polymer and polyelectrolyte decreases the already ultralow interfacial tension.
      This is demonstrated in experiments on aqueous mixtures of dextran (neutral) and
      nongelling fish gelatin (charged). Upon phase separation, electric charge and a
      potential difference develop spontaneously at the interface, decreasing the
      interfacial tension purely electrostatically in a way that can be accounted for
      quantitatively by Poisson-Boltzmann theory. Interfacial tension is a key property
      when it comes to manipulating the water-water interface, for instance to create
      novel water-in-water emulsions. 

PMID- 26317749
TI  - Generalization of Pairwise Models to non-Markovian Epidemics on Networks.
AB  - In this Letter, a generalization of pairwise models to non-Markovian epidemics on
      networks is presented. For the case of infectious periods of fixed length, the
      resulting pairwise model is a system of delay differential equations, which shows
      excellent agreement with results based on stochastic simulations. Furthermore, we
      analytically compute a new R_{0}-like threshold quantity and an analytical
      relation between this and the final epidemic size. Additionally, we show that the
      pairwise model and the analytic results can be generalized to an arbitrary
      distribution of the infectious times, using integro-differential equations, and
      this leads to a general expression for the final epidemic size. By showing the
      rigorous link between non-Markovian dynamics and pairwise delay differential
      equations, we provide the framework for a more systematic understanding of non
      Markovian dynamics. 

PMID- 26317714
TI  - Observation of J/psip Resonances Consistent with Pentaquark States in
      Lambda_{b}^{0}->J/psiK^{-}p Decays.
AB  - Observations of exotic structures in the J/psip channel, which we refer to as
      charmonium-pentaquark states, in Lambda_{b}^{0}->J/psiK^{-}p decays are
      presented. The data sample corresponds to an integrated luminosity of 3 fb^{-1}
      acquired with the LHCb detector from 7 and 8 TeV pp collisions. An amplitude
      analysis of the three-body final state reproduces the two-body mass and angular
      distributions. To obtain a satisfactory fit of the structures seen in the J/psip
      mass spectrum, it is necessary to include two Breit-Wigner amplitudes that each
      describe a resonant state. The significance of each of these resonances is more
      than 9 standard deviations. One has a mass of 4380+/-8+/-29 MeV and a width of
      205+/-18+/-86 MeV, while the second is narrower, with a mass of 4449.8+/-1.7+/
      2.5 MeV and a width of 39+/-5+/-19 MeV. The preferred J^{P} assignments are of
      opposite parity, with one state having spin 3/2 and the other 5/2.

PMID- 26317750
TI  - Gender Differences in Patients with Takotsubo Cardiomyopathy: Multi-Center
      Registry from Tokyo CCU Network.
AB  - BACKGROUND: The clinical features of gender differences in takotsubo
      cardiomyopathy (TC) remain to be determined. The aim of this study was to
      evaluate the differences in clinical characteristics of male and female patients
      with TC. METHODS: We obtained the clinical information of 368 patients diagnosed
      with TC (84 male, 284 female) from the Tokyo CCU Network database collected from
      1 January 2010 to 31 December 2012; the Network is comprised of 71 cardiovascular
      centers in the Tokyo (Japan) metropolitan area. We attempted to characterize
      clinical differences during hospitalization, comparing male and female patients
      with TC. RESULTS: There were no significant differences in apical ballooning
      type, median echocardiography ejection fraction, serious ventricular arrhythmias
      (such as ventricular tachycardia or fibrillation), or cardiovascular death
      between male and female patients. Male patients were younger than female patients
      (median age at hospitalization for male patients was 72 years vs. 76 years for
      female patients; p = 0.040). Prior physical stress was more common in male than
      female patients (50.0% vs.31.3%; p = 0.002), while emotional stress was more
      common in female patients (19.0% vs. 31.0%; p = 0.039). Severe pump failure
      (defined as Killip Class > III) (20.2% vs. 10.6%; p = 0.020) and cardiopulmonary
      supportive therapies (28.6% vs. 12.7%, p < 0.001) were more common in male than
      female patients. Multivariate analysis revealed that male gender (odds ratio =
      4.32, 95% CI = 1.41-13.6, p = 0.011) was an independent predictor of adverse
      composite cardiac events, including cardiovascular death, severe pump failure,
      and serious ventricular arrhythmia. CONCLUSIONS: Cardiac complications in our
      dataset appeared to be more common in male than female patients with TC during
      their hospitalization. Further investigation is required to clarify the
      underlying mechanisms responsible for the observed gender differences.

PMID- 26317752
TI  - Copper, indium, tin, and lead complexes with fluorinated selenolate ligands:
      precursors to MSex.
AB  - Reductive cleavage of C6F5SeSeC6F5 with elemental M (M = Cu, In, Sn, Pb) in
      pyridine results in the formation of (py)4Cu2(SeC6F5)2, (py)2In(SeC6F5)3,
      (py)2Sn(SeC6F5)2, and (py)2Pb(SeC6F5)2. Each group adopts a unique structure: the
      Cu(I) compound crystallizes as a dimer with a pair of bridging selenolates, two
      pyridine ligands coordinating to each Cu(I) ion, and a short Cu(I)-Cu(I) distance
      (2.595 A). The indium compound crystallizes as monometallic five-coordinate
      (py)2In(SeC6F5)3 in a geometry that approximates a trigonal bipyramidal structure
      with two axial pyridine ligands and three selenolates. The tin and lead
      derivatives (py)2M(SeC6F5)2 are also monomeric, but they adopt nearly octahedral
      geometries with trans pyridine ligands, a pair of cis-selenolates, and two
      "empty" cis-positions on the octahedron that are oriented toward extremely remote
      selenolates (M-Se = 3.79 A (Sn), 3.70 A (Pb)) from adjacent molecules. Two of the
      four compounds (Cu, In) exhibit intermolecular pi-pi stacking arrangements in the
      solid state, whereas the stacking of molecules for the other two compounds (Sn,
      Pb) appears to be based upon molecular shape and crystal packing forces. All
      compounds are volatile and decompose at elevated temperatures to give MSex and
      Se(C6F5)2.The electronic structures of the dimeric Cu compound and monomeric
      (py)2M(SeC6F5)2 (M = Sn, Pb) were examined with density functional theory
      calculations. 

PMID- 26317753
TI  - Lewis Acid Mediated Tandem Reaction of Propargylic Alcohols with Hydroxylamine
      Hydrochloride To Give alpha,beta-Unsaturated Amides and Alkenyl Nitriles.
AB  - We have developed a highly selective method for the synthesis of alpha,beta
      unsaturated amides and alkenyl nitriles from readily available propargylic
      alcohols. The reaction proceeded smoothly under the neutral conditions with
      hydroxylamine hydrochloride (NH2OH.HCl) as the nitrogen source. The development
      of these new strategies has significantly extended the application of
      hydroxylamine hydrochloride to the chemistry of propargylic alcohols. Moreover,
      both secondary and tertiary alcohols have been highly regioselectively
      transformed to the desired products with good functional group compatibility. 

PMID- 26317751
TI  - The Ecuadorian Artisanal Fishery for Large Pelagics: Species Composition and
      Spatio-Temporal Dynamics.
AB  - The artisanal fisheries of Ecuador operate within one of the most dynamic and
      productive marine ecosystems of the world. This study investigates the catch
      composition of the Ecuadorian artisanal fishery for large pelagic fishes,
      including aspects of its spatio-temporal dynamics. The analyses of this study are
      based on the most extensive dataset available to date for this fishery: a total
      of 106,963 trip-landing inspection records collected at its five principal ports
      during 2008 - 2012. Ecuadorian artisanal fisheries remove a substantial amount of
      biomass from the upper trophic-level predatory fish community of the eastern
      tropical Pacific Ocean. It is estimated that at least 135 thousand metric tons
      (mt) (about 15.5 million fish) were landed in the five principal ports during the
      study period. The great novelty of Ecuadorian artisanal fisheries is the "oceanic
      artisanal" fleet component, which consists of mother-ship (nodriza) boats with
      their towed fiber-glass skiffs (fibras) operating with pelagic longlines. This
      fleet has fully expanded into oceanic waters as far offshore as 100 degrees W,
      west of the Galapagos Archipelago. It is estimated that nodriza operations
      produce as much as 80% of the total catches of the artisanal fishery. The
      remainder is produced by independent fibras operating in inshore waters with
      pelagic longlines and/or surface gillnets. A multivariate regression tree
      analysis was used to investigate spatio-environmental effects on the nodriza
      fleet (n = 6,821 trips). The catch species composition of the nodriza fleet is
      strongly influenced by the northwesterly circulation of the Humboldt Current
      along the coast of Peru and its associated cold waters masses. The target species
      and longline gear-type used by nodrizas change seasonally with the incursion of
      cool waters (< 25 degrees C) from the south and offshore. During this season,
      dolphinfish (Coryphaena hippurus) dominates the catches. However, in warmer
      waters, the fishery changes to tuna-billfish-shark longline gear and the catch
      composition becomes much more diverse. 

PMID- 26317754
TI  - Does the Effect of Micro-Environmental Factors on a Street's Appeal for Adults'
      Bicycle Transport Vary across Different Macro-Environments? An Experimental
      Study.
AB  - BACKGROUND: Characteristics of the physical environment can be classified into
      two broad categories: macro- ("raw" urban planning features influenced on a
      regional level) and micro- (features specifically within a streetscape influenced
      on a neighborhood level) environmental factors. In urban planning applications,
      it is more feasible to modify conditions at the neighborhood level than at the
      regional level. Yet for the promotion of bicycle transport we need to know
      whether relationships between micro-environmental factors and bicycle transport
      depend on different types of macro-environments. This study aimed to identify
      whether the effect of three micro-environmental factors (i.e., evenness of the
      cycle path surface, speed limits and type of separation between cycle path and
      motorized traffic) on the street's appeal for adults' bicycle transport varied
      across three different macro-environments (i.e., low, medium and high residential
      density street). METHODS: In total, 389 middle-aged adults completed a web-based
      questionnaire consisting of socio-demographic characteristics and a series of
      choice tasks with manipulated photographs, depicting two possible routes to cycle
      along. Conjoint analysis was used to analyze the data. RESULTS: Although the
      magnitude of the overall effects differed, in each macro-environment (i.e., low,
      medium and high residential density), middle-aged adults preferred a speed limit
      of 30 km/h, an even cycle path surface and a hedge as separation between
      motorized traffic and the cycle path compared to a speed limit of 50 or 70 km/h,
      a slightly uneven or uneven cycle path surface and a curb as separation or no
      separation between motorized traffic and the cycle path. CONCLUSIONS: Our results
      suggest that irrespective of the macro-environment, the same micro-environmental
      factors are preferred in middle-aged adults concerning the street's appeal for
      bicycle transport. The controlled environment simulations in the experimental
      choice task have the potential to inform real life environmental interventions
      and suggest that micro-environmental changes can have similar results in
      different macro-environments.

PMID- 26317755
TI  - Consideration of Viral Resistance for Optimization of Direct Antiviral Therapy of
      Hepatitis C Virus Genotype 1-Infected Patients.
AB  - Different highly effective interferon-free treatment options for chronic
      hepatitis C virus (HCV) infection are currently available. Pre-existence of
      resistance associated variants (RAVs) to direct antiviral agents (DAAs) reduces
      sustained virologic response (SVR) rates by 3-53% in hepatitis C virus (HCV)
      genotype 1 infected patients depending on different predictors and the DAA
      regimen used. Frequencies of single and combined resistance to NS3, NS5A and NS5B
      inhibitors and consequences for the applicability of different treatment regimens
      are unknown. Parallel population based sequencing of HCV NS3, NS5A and NS5B genes
      in 312 treatment-naive Caucasian HCV genotype 1 infected patients showed the
      presence of major resistant variants in 20.5% (NS3), 11.9% (NS5A), and 22.1%
      (NS5B) with important differences for HCV subtypes. In NS3, Q80K was observed in
      34.7% and 2.1% of subtype 1a and 1b patients, respectively while other RAVs to
      second generation protease inhibitors were detected rarely (1.4%). Within NS5A
      RAVs were observed in 7.1% of subtype 1a and 17.6% in subtype 1b infected
      patients. RAVs to non-nucleoside NS5B inhibitors were observed in 3.5% and 44.4%
      of subtype 1a and 1b patients, respectively. Considering all three DAA targets
      all subtype 1a and 98.6% of subtype 1b infected patients were wildtype for at
      least one interferon free DAA regimen currently available. In conclusion,
      baseline resistance testing allows the selection of at least one RAVs-free
      treatment option for nearly all patients enabling a potentially cost- and
      efficacy-optimized treatment of chronic hepatitis C. 

PMID- 26317757
TI  - Exploratory Metabolomic Analyses Reveal Compounds Correlated with Lutein
      Concentration in Frontal Cortex, Hippocampus, and Occipital Cortex of Human
      Infant Brain.
AB  - Lutein is a dietary carotenoid well known for its role as an antioxidant in the
      macula, and recent reports implicate a role for lutein in cognitive function.
      Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue.
      In addition, cognitive function in older adults correlated with macular and
      postmortem brain lutein concentrations. Furthermore, lutein was found to
      preferentially accumulate in the infant brain in comparison to other carotenoids
      that are predominant in diet. While lutein is consistently related to cognitive
      function, the mechanisms by which lutein may influence cognition are not clear.
      In an effort to identify potential mechanisms through which lutein might
      influence neurodevelopment, an exploratory study relating metabolite signatures
      and lutein was completed. Post-mortem metabolomic analyses were performed on
      human infant brain tissues in three regions important for learning and memory:
      the frontal cortex, hippocampus, and occipital cortex. Metabolomic profiles were
      compared to lutein concentration, and correlations were identified and reported
      here. A total of 1276 correlations were carried out across all brain regions. Of
      427 metabolites analyzed, 257 were metabolites of known identity. Unidentified
      metabolite correlations (510) were excluded. In addition, moderate correlations
      with xenobiotic relationships (2) or those driven by single outliers (3) were
      excluded from further study. Lutein concentrations correlated with lipid pathway
      metabolites, energy pathway metabolites, brain osmolytes, amino acid
      neurotransmitters, and the antioxidant homocarnosine. These correlations were
      often brain region-specific. Revealing relationships between lutein and metabolic
      pathways may help identify potential candidates on which to complete further
      analyses and may shed light on important roles of lutein in the human brain
      during development. 

PMID- 26317758
TI  - Trans-Corneal Subretinal Injection in Mice and Its Effect on the Function and
      Morphology of the Retina.
AB  - PURPOSE: To introduce a practical method of subretinal injection in mice and
      evaluate injection-induced retinal detachment (RD) and damage using a dynamic
      imaging system, electrophysiology, and histology. METHODS: After full dilation of
      a 2-month-old C57BL/6J mouse pupil, the cornea near the limbus was punctured with
      a 30 1/2-gague disposable beveled needle. A 33 1/2-gauge blunt needle was
      inserted through the corneal perforation into the anterior chamber, avoiding the
      lens before going deeper into the vitreous cavity, and penetrating the inner
      retina to reach the subretinal space. The mice were divided into four groups: in
      group 1, about 80-100% of the retina was filled with subretinally injected
      solution; in group 2, approximately 50-70% of the retina was filled with injected
      solution; in group 3, the procedures were stopped before solution injection; and
      non-injected eyes were used as the negative control in group 4. An optical
      coherence tomography (OCT) imaging system was used to monitor retinal
      reattachment during the first three days following the injections. Histological
      and functional changes were examined by light microscopy and electroretinography
      (ERG) at five weeks post-injection. RESULTS: After a short-term training, a 70%
      success rate with 50% or more coverage (i.e., retinal blebs occupied 50% or more
      retinal area and filled with the injected solution) with minimal injection
      related damages can be achieved. Bleb formation was associated with retinal
      detachment (RD) between the neuroretina and the retinal pigment epithelium (RPE)
      layer. Partial RD could be observed at post-injection day 1, and by day 2 most of
      the retina had reattached. At 5 weeks post-injection, compared to uninjected
      control group 4, the b-wave amplitudes of ERG decreased 22% in group 1, 16% in
      group 2, and 7% in group 3; the b-wave amplitudes were statistically different
      between the uninjected group and the groups with either 50-70% or 80-100%
      coverage. The subretinal injection-induced RD reattached and became stable at
      five weeks post-injection, although some photoreceptor damage could still be
      observed in and around the injection sites, especially in 80-100% coverage group.
      CONCLUSIONS: Trans-corneal subretinal injection is effective and practical,
      although subretinal injection-related damages can cause some morphological and
      functional loss.

PMID- 26317761
TI  - Potential scenarios leading to ovarian cancer arising from endometriosis.
AB  - OBJECTIVES: The aim of this review was to highlight recent advances in our
      understanding of the pathogenesis of malignant transformation of endometriosis.
      METHODS: This study reviewed the English-language literature concerning basic
      science studies of the potential promotion of carcinogenesis. RESULTS: Repeated
      episodes of hemorrhage occur in endometriosis at the onset of menstruation.
      Extracellular hemoglobin, heme, and iron derivatives in endometriosis cause DNA
      damage and mutations, which create increased cellular susceptibility to oxidant
      mediated cell killing. Excess DNA damage and mutations are linked to cell death,
      but not carcinogenesis. In response to an oxidative and inflammatory
      microenvironment, endometriotic cells and macrophages secrete antioxidants that
      control excess oxidative stress in the surrounding environment. Exposure of
      endometriotic cells to a sublethal level of oxidative stress may lead to
      carcinogenesis. Macrophages also secrete immunosuppressive factors that lead to
      promotion of malignant transformation. DISCUSSION: At least two potential
      scenarios could result in ovarian cancer arising from endometriosis. The first
      step: extracellular hemoglobin, heme, and iron cause cellular oxidative damage by
      promoting reactive oxygen species formation, which results in DNA damage and
      mutations (ovarian cancer initiation from endometriosis). The second step: cancer
      progression may be associated with persistent antioxidant production favoring a
      protumoral microenvironment.

PMID- 26317760
TI  - Bile Salts Modulate the Mucin-Activated Type VI Secretion System of Pandemic
      Vibrio cholerae.
AB  - The causative agent of cholera, Vibrio cholerae, regulates its diverse virulence
      factors to thrive in the human small intestine and environmental reservoirs.
      Among this pathogen's arsenal of virulence factors is the tightly regulated type
      VI secretion system (T6SS). This system acts as an inverted bacteriophage to
      inject toxins into competing bacteria and eukaryotic phagocytes. V. cholerae
      strains responsible for the current 7th pandemic activate their T6SS within the
      host. We established that T6SS-mediated competition occurs upon T6SS activation
      in the infant mouse, and that this system is functional under anaerobic
      conditions. When investigating the intestinal host factors mucins (a glycoprotein
      component of mucus) and bile for potential regulatory roles in controlling the
      T6SS, we discovered that once mucins activate the T6SS, bile acids can further
      modulate T6SS activity. Microbiota modify bile acids to inhibit T6SS-mediated
      killing of commensal bacteria. This interplay is a novel interaction between
      commensal bacteria, host factors, and the V. cholerae T6SS, showing an active
      host role in infection. 

PMID- 26317759
TI  - Association of ADORA1 rs2228079 and ADORA2A rs5751876 Polymorphisms with Gilles
      de la Tourette Syndrome in the Polish Population.
AB  - BACKGROUND: Gilles de la Tourette syndrome (GTS) is a neurodevelopmental disorder
      characterized by motor and vocal tics. Hyperactivity of dopaminergic transmission
      is considered a prime abnormality in the pathophysiology of tics. There are
      reciprocal antagonistic interactions between adenosine and dopamine transmission.
      The aim of the study was to analyze the association of two polymorphisms,
      rs2228079 in ADORA1 and rs5751876 in ADORA2A, with the risk of GTS and co-morbid
      disorders. MATERIAL AND METHODS: A total of 162 Polish GTS patients and 270
      healthy persons were enrolled in the study. Two polymorphisms were selected on
      the basis of knowledge of SNPs frequencies in ADORA1 and ADORA2A. Chi-square test
      was used for allelic and genotypic association studies. Association of genotypes
      with age of tic onset was analyzed with Mann-Whitney test. Multivariate logistic
      regression was used to find independent predictors of GTS risk. RESULTS: We found
      that the risk of GTS was associated with rs2228079 and rs5751876 polymorphisms.
      The GG+GT genotypes of rs2228079 in ADORA1 were underrepresented in GTS patients
      (p = 0.011), whereas T allele of rs5751876 in ADORA2A was overrepresented (p =
      0.017). The GG genotype of rs2228079 was associated with earlier age of tic onset
      (p = 0.046). We found also that the minor allele G of rs2228079 was more frequent
      in GTS patients with depression as compared to the patients without depression (p
      = 0.015). Also the genotype GG was significantly more frequent in patients with
      obsessive compulsive disorder/behavior (OCD/OCB, p = 0.021) and depression (p =
      0.032), as compared to the patients without these co-morbidities. The minor
      allele T frequency of rs5751876 was lower in GTS patients with co-morbid
      attention deficit hyperactivity disorder (p = 0.022), and TT+TC genotypes were
      less frequent in the non-OCD anxiety disorder group (p = 0.045). CONCLUSION:
      ADORA1 and ADORA2A variants are associated with the risk of GTS, co-morbid
      disorders, and may affect the age of tic onset.

PMID- 26317756
TI  - Glycosylated Porphyrins, Phthalocyanines, and Other Porphyrinoids for Diagnostics
      and Therapeutics.

PMID- 26317763
TI  - Social Work Intervention Research With Adult Cancer Patients: A Literature Review
      and Reflection on Knowledge-Building for Practice.
AB  - The results of a literature review of social work intervention research with
      adult cancer patients found only a small number of studies conducted by social
      work researchers. The findings of the review are presented followed by a
      reflective discussion on the nature of knowledge-building and research knowledge
      for practice. Knowledge building is considered as a continuous, negotiated
      process within communities of practice focused on psychosocial perspectives that
      draw on a range of knowledge sources. Epistemology, worldviews and research
      orientations are considered along with the values and stance of social work, all
      of which create the domain of the practice-researcher. 

PMID- 26317762
TI  - Predicting Patient Advocacy Engagement: A Multiple Regression Analysis Using Data
      From Health Professionals in Acute-Care Hospitals.
AB  - Although literature documents the need for hospital social workers, nurses, and
      medical residents to engage in patient advocacy, little information exists about
      what predicts the extent they do so. This study aims to identify predictors of
      health professionals' patient advocacy engagement with respect to a broad range
      of patients' problems. A cross-sectional research design was employed with a
      sample of 94 social workers, 97 nurses, and 104 medical residents recruited from
      eight hospitals in Los Angeles. Bivariate correlations explored whether seven
      scales (Patient Advocacy Eagerness, Ethical Commitment, Skills, Tangible Support,
      Organizational Receptivity, Belief Other Professionals Engage, and Belief the
      Hospital Empowers Patients) were associated with patient advocacy engagement,
      measured by the validated Patient Advocacy Engagement Scale. Regression analysis
      examined whether these scales, when controlling for sociodemographic and setting
      variables, predicted patient advocacy engagement. While all seven predictor
      scales were significantly associated with patient advocacy engagement in
      correlational analyses, only Eagerness, Skills, and Belief the Hospital Empowers
      Patients predicted patient advocacy engagement in regression analyses.
      Additionally, younger professionals engaged in higher levels of patient advocacy
      than older professionals, and social workers engaged in greater patient advocacy
      than nurses. Limitations and the utility of these findings for acute-care
      hospitals are discussed. 

PMID- 26317764
TI  - The Determination of Self-Control Skill of Tuberculosis Patients According to
      Some Variables.
AB  - This study was conducted in Ankara, Turkey. In the study, questionnaire form and
      Self-Control Schedule (SCS) was used. According to the t-test, statistically
      significant difference between self-control skill and "support of family members
      to each other" was found. Analysis showed that the occupational status and
      educational level had a significant effect on self-control skill. Besides, there
      is a positive relationship between average monthly income and self-control skill,
      while there is a negative correlation among number of hospitalizations, diagnosis
      period, and self-control skill. Our results may be a guide to develop more
      effective intervention strategies for tuberculosis management. 

PMID- 26317765
TI  - Professional Distress and Meaning in Health Care: Why Professional Empathy Can
      Help.
AB  - For human service care providers working in hospitals, balancing the motivation
      for interpersonal engagement with patients alongside self-protective emotional
      boundaries is a familiar struggle. Empathy is a critical, although not thoroughly
      understood, aspect of patient care as well as an important ingredient for feeling
      work satisfaction and meaning. However, empathy can lead to feelings of
      sympathetic emotional distress and even burnout. This article uses an
      illustrative case study from a medical social worker in the emergency room to
      explore these themes of empathy, burnout, and the search for meaning in work. The
      discussion examines areas for further empirical study and intervention to support
      care-provider empathy and avoid burnout. 

PMID- 26317766
TI  - Stressors and Caregivers' Depression: Multiple Mediators of Self-Efficacy, Social
      Support, and Problem-Solving Skill.
AB  - Caring for an older adult with memory loss is stressful. Caregiver stress could
      produce negative outcomes such as depression. Previous research is limited in
      examining multiple intermediate pathways from caregiver stress to depressive
      symptoms. This study addresses this limitation by examining the role of self
      efficacy, social support, and problem solving in mediating the relationships
      between caregiver stressors and depressive symptoms. Using a sample of 91 family
      caregivers, we tested simultaneously multiple mediators between caregiver
      stressors and depression. Results indicate that self-efficacy mediated the
      pathway from daily hassles to depression. Findings point to the importance of
      improving self-efficacy in psychosocial interventions for caregivers of older
      adults with memory loss. 

PMID- 26317767
TI  - A Comparison of Young, Middle-Aged, and Older Uninsured Individuals in the United
      States: Health Beliefs and Satisfaction With Providers.
AB  - This study compared three age groups of uninsured adults, young (26-44), middle
      aged (45-64), and older (65>=), to examine heterogeneity of the uninsured. The
      pooled 2000-2007 Medical Expenditure Panel Survey was analyzed (N = 22,246). The
      findings demonstrated that the three groups were very different regarding their
      individual characteristics, health service utilization, and health beliefs.
      Compared with uninsured young adults, uninsured middle-aged individuals reported
      worse health statuses, paid higher out-of-pocket medical expenditures, and had
      more positive attitudes toward insurance and health care. Considering the policy
      goals of the Affordable Care Act, understanding the uninsured by age will
      facilitate targeted interventions to decrease the number of uninsured. 

PMID- 26317768
TI  - Can We Use Tree Rings of Black Alder to Reconstruct Lake Levels? A Case Study for
      the Mecklenburg Lake District, Northeastern Germany.
AB  - In this study, we explore the potential to reconstruct lake-level (and
      groundwater) fluctuations from tree-ring chronologies of black alder (Alnus
      glutinosa L.) for three study lakes in the Mecklenburg Lake District,
      northeastern Germany. As gauging records for lakes in this region are generally
      short, long-term reconstructions of lake-level fluctuations could provide
      valuable information on past hydrological conditions, which, in turn, are useful
      to assess dynamics of climate and landscape evolution. We selected black alder as
      our study species as alder typically thrives as riparian vegetation along
      lakeshores. For the study lakes, we tested whether a regional signal in lake
      level fluctuations and in the growth of alder exists that could be used for long
      term regional hydrological reconstructions, but found that local (i.e. site
      specific) signals in lake level and tree-ring chronologies prevailed. Hence, we
      built lake/groundwater-level reconstruction models for the three study lakes
      individually. Two sets of models were considered based on (1) local tree-ring
      series of black alder, and (2) site-specific Standardized Precipitation
      Evapotranspiration Indices (SPEI). Although the SPEI-based models performed
      statistically well, we critically reflect on the reliability of these
      reconstructions, as SPEI cannot account for human influence. Tree-ring based
      reconstruction models, on the other hand, performed poor. Combined, our results
      suggest that, for our study area, long-term regional reconstructions of lake
      level fluctuations that consider both recent and ancient (e.g., archaeological)
      wood of black alder seem extremely challenging, if not impossible. 

PMID- 26317769
TI  - Coupling of Caged Molecule Dynamics to JG beta-Relaxation II: Polymers.
AB  - At temperatures below the nominal glass transition temperature Tgalpha, the
      structural alpha-relaxation and the Johari-Goldstein (JG) beta-relaxation are too
      slow to contribute to susceptibility measured at frequencies higher than 1 GHz.
      This is particularly clear in the neighborhood of the secondary glass transition
      temperature Tgbeta, which can be obtained directly by positronium annihilation
      lifetime spectroscopy (PALS) and adiabatic calorimetry, or deduced from the
      temperature at which the JG beta-relaxation time taubeta reaches 1000 s. The fast
      process at such high frequencies comes from the vibrations and caged molecules
      dynamics manifested as the nearly constant loss (NCL) in susceptibility
      measurements, elastic scattering intensity, I(Q, T), or the mean-square
      displacement, ?u(2)(T)?, in quasielastic neutron scattering experiment.
      Remarkably, we find for many different glass-formers that the NCL, I, or ?u(2)?
      measured in the glassy state changes its temperature dependence at temperature
      THF near Tgbeta. In paper I (Capaccioli, S.; et al. J. Phys. Chem. B 2015, 119
      (28), 8800-8808) we have made known this property in the case of the polyalcohols
      and a pharmaceutical glass former, flufenamic acid studied by THz dielectric
      spectroscopy, and explained it by the coupling of the NCL to the JG beta
      relaxation, and the density dependence of these processes. In this paper II, we
      extend the consideration of the high frequency response to broader range from 100
      MHz to THz in the glassy state of many polymers observed by quasielastic light
      scattering, Brillouin scattering, quasielastic neutron scattering, and GHz-THz
      dielectric relaxation. In all cases, the NCL changes its T-dependence at some
      temperature, THF, below Tgalpha, which is approximately the same as Tgbeta. The
      latter is independently determined by PALS, or adiabatic calorimetry, or low
      frequency dielectric and mechanical spectroscopy. The property, THF ~ Tgbeta, had
      not been pointed out before by others or in any of the quasielastic neutron and
      light scattering studies of various amorphous polymers and van der Waals small
      molecular glass-formers over the past three decades. The generality and
      fundamental importance of this novel property revitalize the data from these
      previous publications, making it necessary to be reckoned with in any attempt to
      solve the glass transition problem. In our rationalization, the property arises
      first from the fact that the JG beta-relaxation and the caged dynamics both
      depends on density and entropy. Second, the JG beta-relaxation is the terminator
      of the caged dynamics, and hence the two processes are inseparable or effectively
      coupled. Consequently, the occurrence of the secondary glass transition at Tgbeta
      necessarily is accompanied by corresponding change in the temperature dependence
      of the NCL, I, or ?u(2)? of the fast caged dynamics at THF ~ Tgbeta. 

PMID- 26317770
TI  - Serological and Progression Differences of Joint Destruction in the Wrist and the
      Feet in Rheumatoid Arthritis - A Cross-Sectional Cohort Study.
AB  - OBJECTIVE: To investigate clinical and radiological differences between joint
      destruction in the wrist and the feet in patients with RA. METHODS: A cross
      sectional clinical study was conducted in an RA cohort at a single institution.
      Clinical data included age, sex and duration of disease. Laboratory data included
      sero-positivity for anti-cyclic citrullinated peptide (CCP) antibody and RF.
      Radiological measurements included Larsen grades and the modified Sharp/van der
      Heijde method (SHS) for the hands/wrists and the feet. Statistical analyses were
      performed using the Kruskal-Wallis H-test, a dummy variable linear regression
      model and multivariate logistic regression analysis with 95% confidence interval
      and odds ratios. RESULTS: A total of 405 patients were enrolled, and 314 patients
      were analysed in this study. The duration of disease in the foot-dominant group
      was significantly less than that in the wrist-dominant group. When patients were
      subdivided by duration of disease, the Larsen grade of the feet was significantly
      higher than that of the wrist in the first quadrant subgroup, but this was
      reversed with increasing duration of disease. Anti-CCP status was a significant
      predictive factor for joint destruction in the wrist but not in the feet, while
      RF status was not predictive in either the wrist or the feet. CONCLUSIONS: Joint
      destruction in the feet started earlier than in the wrist, but the latter
      progresses faster with increasing duration of disease. Anti-CCP status predicts
      joint destruction in the wrist better than in the feet.

PMID- 26317771
TI  - The Fibrin Matrix Regulates Angiogenic Responses within the Hemostatic
      Microenvironment through Biochemical Control.
AB  - Conceptually, premature initiation of post-wound angiogenesis could interfere
      with hemostasis, as it relies on fibrinolysis. The mechanisms facilitating
      orchestration of these events remain poorly understood, however, likely due to
      limitations in discerning the individual contribution of cells and extracellular
      matrix. Here, we designed an in vitro Hemostatic-Components-Model (HCM) to
      investigate the role of the fibrin matrix as protein factor-carrier, independent
      of its cell-scaffold function. After characterizing the proteomic profile of HCM
      harvested matrix releasates, we demonstrate that the key pro-/anti-angiogenic
      factors, VEGF and PF4, are differentially bound by the matrix. Changing matrix
      fibrin mass consequently alters the balance of releasate factor concentrations,
      with differential effects on basic endothelial cell (EC) behaviors. While
      increasing mass, and releasate VEGF levels, promoted EC chemotactic migration, it
      progressively inhibited tube formation, a response that was dependent on PF4.
      These results indicate that the clot's matrix component initially serves as
      biochemical anti-angiogenic barrier, suggesting that post-hemostatic angiogenesis
      follows fibrinolysis-mediated angiogenic disinhibition. Beyond their significance
      towards understanding the spatiotemporal regulation of wound healing, our
      findings could inform the study of other pathophysiological processes in which
      coagulation and angiogenesis are prominent features, such as cardiovascular and
      malignant disease. 

PMID- 26317772
TI  - Insect Consumption to Address Undernutrition, a National Survey on the Prevalence
      of Insect Consumption among Adults and Vendors in Laos.
AB  - BACKGROUND: Insect consumption (entomophagy) is a potentially high nutritious and
      healthy source of food with high fat, protein, vitamin, fiber and micronutrient
      content. At least 2 billion people globally eat insects (over 1900 edible
      species) though this habit is regarded negatively by others. There is a limited
      amount of data on the perception and consumption of insects. We conducted a
      national cross-sectional survey in the Lao People's Democratic Republic (Laos) to
      assess the prevalence and characteristics of insect consumption among adult lay
      people and insect vendors. METHODS: We conducted a multi stage randomized
      national survey in 1303 households in 96 villages in 16 Lao provinces. Three
      insect vendors or collectors per village were also included. A standardized
      pretested questionnaire addressed the following issues: socioeconomic
      characteristics, type of insects consumed and frequency of consumption, reasons
      and trends in consumption as well as reports on side effects, over the last 10
      years. RESULTS: A total of 1059 adults (Sex ratio F/M: 1.2, 30 ethnic groups),
      and 256 vendors were enrolled. A total of 1025 (96.8%) lay people were currently
      insect consumers, 135 (13.0%) daily or weekly consumers, and 322 (31.1%) consumed
      several times per month. For the majority (575, 55.6%) the consumption was
      infrequent (less than a few times per year) and only 22 (2%) had never eaten
      insects. Consumption started in childhood. Insect availability was seasonal (670,
      63.2%) and respondents would have eaten more insects, if they had been more
      available (919, 86.7%). Hmong and Leu ethnic groups had significantly lower
      consumption levels than the general population. Eggs of weaver ants, short-tailed
      crickets, crickets, grasshoppers, and cicadas were the top 5 insects consumed.
      Consumption had decreased in the last decade, mostly due to less availability
      (869; 84.0%) and change of life (29; 5.5%). Of 1059, 80 (7.5%) reported allergy
      problems and 106 (10.0%) reported some use in traditional medicine. A total of
      874 (82.6%) were regular collectors. Insect vendors (Sex ratio F/M: 5.3) were
      also collectors (185; 72.2%). They dedicated a mean time of 4.7 hours during the
      last harvesting period. The majority sold insects at markets (141, 55.0%). They
      had earned, on average, USD 6.0 the day before. Five insects (weaver ant eggs;
      bamboo worms; short-tailed crickets; crickets; wasps) represented 85% of the
      market. CONCLUSION: Entomophagy is general in Laos, and well accepted despite a
      decreasing trend in consumption over the last decade. Its contribution to the Lao
      diet is limited to a minority of frequent consumers. Income through insect sales
      benefits mostly women. Consumption varies according to ethnicity, residence and
      season. Development of insect farming is still at an early stage. It could
      however increase availability of insects and contribute to the generation of
      income.

PMID- 26317773
TI  - Are There Age-Related Differences in the Ability to Learn Configural Responses?
AB  - Age is often associated with a decline in cognitive abilities that are important
      for maintaining functional independence, such as learning new skills. Many forms
      of motor learning appear to be relatively well preserved with age, while learning
      tasks that involve associative binding tend to be negatively affected. The
      current study aimed to determine whether age differences exist on a configural
      response learning task, which includes aspects of motor learning and associative
      binding. Young (M = 24 years) and older adults (M = 66.5 years) completed a
      modified version of a configural learning task. Given the requirement of
      associative binding in the configural relationships between responses, we
      predicted older adults would show significantly less learning than young adults.
      Older adults demonstrated lower performance (slower reaction time and lower
      accuracy). However, contrary to our prediction, older adults showed similar rates
      of learning as indexed by a configural learning score compared to young adults.
      These results suggest that the ability to acquire knowledge incidentally about
      configural response relationships is largely unaffected by cognitive aging. The
      configural response learning task provides insight into the task demands that
      constrain learning abilities in older adults. 

PMID- 26317774
TI  - In Vivo Evaluation of Cervical Stiffness Evolution during Induced Ripening Using
      Shear Wave Elastography, Histology and 2 Photon Excitation Microscopy: Insight
      from an Animal Model.
AB  - Prematurity affects 11% of the births and is the main cause of infant mortality.
      On the opposite case, the failure of induction of parturition in the case of
      delayed spontaneous birth is associated with fetal suffering. Both conditions are
      associated with precocious and/or delayed cervical ripening. Quantitative and
      objective information about the temporal evolution of the cervical ripening may
      provide a complementary method to identify cases at risk of preterm delivery and
      to assess the likelihood of successful induction of labour. In this study, the
      cervical stiffness was measured in vivo in pregnant sheep by using Shear Wave
      Elastography (SWE). This technique assesses the stiffness of tissue through the
      measurement of shear waves speed (SWS). In the present study, 9 pregnant ewes
      were used. Cervical ripening was induced at 127 days of pregnancy (term: 145
      days) by dexamethasone injection in 5 animals, while 4 animals were used as
      control. Elastographic images of the cervix were obtained by two independent
      operators every 4 hours during 24 hours after injection to monitor the cervical
      maturation induced by the dexamethasone. Based on the measurements of SWS during
      vaginal ultrasound examination, the stiffness in the second ring of the cervix
      was quantified over a circular region of interest of 5 mm diameter. SWS was found
      to decrease significantly in the first 4-8 hours after dexamethasone compared to
      controls, which was associated with cervical ripening induced by dexamethasone
      (from 1.779 m/s +/- 0.548 m/s, p < 0.0005, to 1.291 m/s +/- 0.516 m/s, p <
      0.000). Consequently a drop in the cervical elasticity was quantified too (from
      9.5 kPa +/- 0.9 kPa, p < 0.0005, to 5.0 kPa +/- 0.8 kPa, p < 0.000). Moreover,
      SWE measurements were highly reproducible between both operators at all times.
      Cervical ripening induced by dexamethasone was confirmed by the significant
      increase in maternal plasma Prostaglandin E2 (PGE2), as evidenced by the assay of
      its metabolite PGEM. Histological analyses and two-photon excitation microscopy,
      combining both Second Harmonic Generation (SHG) and Two-photon Fluorescence
      microscopy (2PF) contrasts, were used to investigate, at the microscopic scale,
      the structure of cervical tissue. Results show that both collagen and 2PF-active
      fibrillar structures could be closely related to the mechanical properties of
      cervical tissue that are perceptible in elastography. In conclusion, SWE may be a
      valuable method to objectively quantify the cervical stiffness and as a
      complementary diagnostic tool for preterm birth and for labour induction success.

PMID- 26317776
TI  - Effects of Fuzheng Paidu tablet on peripheral blood T lymphocytes, intestinal
      mucosa T lymphocytes, and immune organs in cyclophosphamide-induced
      immunosuppressed mice.
AB  - OBJECTIVE: The aim of this study is to investigate the effects of a Fuzheng Paidu
      tablet on peripheral blood T lymphocytes, intestinal mucosa T lymphocytes, and
      immune organs in cyclophosphamide (CY)-induced immunosuppressed mice. METHODS:
      The experimental mice (but not the control mice) were intraperitoneally injected
      with 80 mg/kg of CY solution every day for 3 consecutive days. Meanwhile, each
      mouse was administered with corresponding drugs for 7 continuous days. Then, 1 h
      after the last administration, each index was detected. RESULTS: The Fuzheng
      Paidu tablet significantly increases the CD4+/CD8+ ratio (P < 0.01) and the
      number of CD3+ and CD4+ cells in immunosuppressed mice (P < 0.01). In addition,
      the tablet apparently enhances the CD3+, CD4+, and CD8+ levels in the intestinal
      mucosal immune system (P < 0.01) as well as reverses the reduction of spleen
      lymphoid nodules and lymphocytes (P < 0.01). It also significantly improves
      intestinal inflammation, thymic atrophy, and sparse thymocytes in
      immunosuppressed mice (P < 0.01). DISCUSSION: The Fuzheng Paidu tablet greatly
      increases the levels of peripheral blood T lymphocytes and intestinal mucosal T
      lymphocytes as well as improves atrophied thymuses and spleens in CY-induced
      immunosuppressed mice.

PMID- 26317775
TI  - Molecular Markers of Tubulointerstitial Fibrosis and Tubular Cell Damage in
      Patients with Chronic Kidney Disease.
AB  - In chronic kidney disease (CKD), progressive nephron loss causes glomerular
      sclerosis, as well as tubulointerstitial fibrosis and progressive tubular injury.
      In this study, we aimed to identify molecular changes that reflected the
      histopathological progression of renal tubulointerstitial fibrosis and tubular
      cell damage. A discovery set of renal biopsies were obtained from 48 patients
      with histopathologically confirmed CKD, and gene expression profiles were
      determined by microarray analysis. The results indicated that hepatitis A virus
      cellular receptor 1 (also known as Kidney Injury Molecule-1, KIM-1), lipocalin 2
      (also known as neutrophil gelatinase-associated lipocalin, NGAL), SRY-box 9, WAP
      four-disulfide core domain 2, and NK6 homeobox 2 were differentially expressed in
      CKD. Their expression levels correlated with the extent of tubulointerstitial
      fibrosis and tubular cell injury, determined by histopathological examination.
      The expression of these 5 genes was also increased as kidney damage progressed in
      a rodent unilateral ureteral obstruction model of CKD. We calculated a molecular
      score using the microarray gene expression profiles of the biopsy specimens. The
      composite area under the receiver operating characteristics curve plotted using
      this molecular score showed a high accuracy for diagnosing tubulointerstitial
      fibrosis and tubular cell damage. The robust sensitivity of this score was
      confirmed in a validation set of 5 individuals with CKD. These findings
      identified novel molecular markers with the potential to contribute to the
      detection of tubular cell damage and tubulointerstitial fibrosis in the kidney. 

PMID- 26317777
TI  - Cold Hardiness of Winter-Acclimated Drosophila suzukii (Diptera: Drosophilidae)
      Adults.
AB  - Drosophila suzukii Matsumura, often called spotted wing drosophila, is an exotic
      vinegar fly that is native to Southeast Asia and was first detected in the
      continental United States in 2008. Previous modeling studies have suggested that
      D. suzukii might not survive in portions of the northern United States or
      southern Canada due to the effects of cold. As a result, we measured two aspects
      of insect cold tolerance, the supercooling point and lower lethal temperature,
      for D. suzukii summer-morph pupae and adults and winter-morph adults.
      Supercooling points were compared to adults of Drosophila melanogaster Meigen.
      The lower lethal temperature of D. suzukii winter-morph adults was significantly
      colder than that for D. suzukii summer-morph adults, while supercooling points of
      D. suzukii winter-morph adults were actually warmer than that for D. suzukii
      summer-morph adults and pupae. D. suzukii summer-morph adult supercooling points
      were not significantly different than those for D. melanogaster adults. These
      measures indicate that D. suzukii is a chill intolerant insect, and winter-morph
      adults are the most cold-tolerant life stage. These results can be used to
      improve predictions of where D. suzukii might be able to establish overwintering
      populations and cause extensive damage to spring fruit crops. 

PMID- 26317778
TI  - Deep Sequencing of the Scutellaria baicalensis Georgi Transcriptome Reveals
      Flavonoid Biosynthetic Profiling and Organ-Specific Gene Expression.
AB  - Scutellaria baicalensis Georgi has long been used in traditional medicine to
      treat various such widely varying diseases and has been listed in the Chinese
      Pharmacopeia, the Japanese Pharmacopeia, the Korean Pharmacopoeia and the
      European Pharmacopoeia. Flavonoids, especially wogonin, wogonoside, baicalin, and
      baicalein, are its main functional ingredients with various pharmacological
      activities. Although pharmaological studies for these flavonoid components have
      been well conducted, the molecular mechanism of their biosynthesis remains
      unclear in S. baicalensis. In this study, Illumina/Solexa deep sequencing
      generated more than 91 million paired-end reads and 49,507 unigenes from S.
      baicalensis roots, stems, leaves and flowers. More than 70% unigenes were
      annotated in at least one of the five public databases and 13,627 unigenes were
      assigned to 3,810 KEGG genes involved in 579 different pathways. 54 unigenes that
      encode 12 key enzymes involved in the pathway of flavonoid biosynthesis were
      discovered. One baicalinase and three baicalein 7-O-glucuronosyltransferases
      genes potentially involved in the transformation between baicalin/wogonoside and
      baicalein/wogonin were identified. Four candidate 6-hydroxylase genes for the
      formation of baicalin/baicalein and one candidate 8-O-methyltransferase gene for
      the biosynthesis of wogonoside/wogonin were also recognized. Our results further
      support the conclusion that, in S. baicalensis, 3,5,7-trihydroxyflavone was the
      precursor of the four above compounds. Then, the differential expression models
      and simple sequence repeats associated with these genes were carefully analyzed.
      All of these results not only enrich the gene resource but also benefit research
      into the molecular genetics and functional genomics in S. baicalensis. 

PMID- 26317779
TI  - Dicarbonyl Induced Structural Perturbations Make Histone H1 Highly Immunogenic
      and Generate an Auto-Immune Response in Cancer.
AB  - Increased oxidative stress under hyperglycemic conditions, through the
      interaction of AGEs with RAGE receptors and via activation of interleukin
      mediated transcription signalling, has been reported in cancer. Proteins
      modifications are being explored for their roles in the development and
      progression of cancer and autoantibody response against them is gaining interest
      as a probe for early detection of the disease. This study has analysed the
      changes in histone H1 upon modification by methylglyoxal (MG) and its
      implications in auto-immunopathogenesis of cancer. Modified histone showed
      modifications in the aromatic residues, changed tyrosine microenvironment,
      intermolecular cross linking and generation of AGEs. It showed masking of
      hydrophobic patches and a hypsochromic shift in the in ANS specific fluorescence.
      MG aggressively oxidized histone H1 leading to the accumulation of reactive
      carbonyls. Far UV CD measurements showed di-carbonyl induced enhancement of the
      alpha structure and the induction of beta sheet conformation; and thermal
      denaturation (Tm) studies confirmed the thermal stability of the modified
      histone. FTIR analysis showed amide I band shift, generation of a carboxyethyl
      group and N-Calpha vibrations in the modified histone. LCMS analysis confirmed
      the formation of Nepsilon-(carboxyethyl)lysine and electron microscopic studies
      revealed the amorphous aggregate formation. The modified histone showed altered
      cooperative binding with DNA. Modified H1 induced high titre antibodies in
      rabbits and the IgG isolated form sera of rabbits immunized with modified H1
      exhibited specific binding with its immunogen in Western Blot analysis. IgG
      isolated from the sera of patients with lung cancer, prostate cancer, breast
      cancer and cancer of head and neck region showed better recognition for neo
      epitopes on the modified histone, reflecting the presence of circulating
      autoantibodies in cancer. Since reports suggest a link between AGE-RAGE axis and
      carcinogenesis, glycoxidation of histone H1 and its immunogenicity paves ways for
      understanding role of glycoxidatively damaged nuclear proteins in cancer. 

PMID- 26317780
TI  - Development of a mechanical model of the human skull bone by morphological study.

PMID- 26317781
TI  - "Carrying Ibuprofen in the Bag": Priority Health Concerns of Latin American
      Migrants in Spain- A Participatory Qualitative Study.
AB  - BACKGROUND: An estimated 2.7 million Latin Americans reside in Europe, mostly in
      Spain. Part of a broader project aimed at developing a research agenda on the
      health status and determinants of this population, this qualitative study engaged
      Latin American migrants in the identification of research priorities. METHODS: We
      conducted 30 group discussions between November 2012-March 2013 with 84
      participants purposively selected for maximum diversity in Madrid and Barcelona
      (Spain). We facilitated sequences of task-oriented visual activities to explore
      their views on priority health concerns. We tape-recorded and transcribed
      discussions and developed a coding frame based on socio-ecological frameworks,
      which we applied to all the data using NVIVO-10. A final round of eight group
      discussions allowed us to triangulate and enrich interpretations by including
      participants' insights. FINDINGS: The cumulative toll of daily stresses was the
      major health concern perceived by a population that conceptualised ill-health as
      a constellation of symptoms rather than as specific diseases. Work-related
      factors, legislative frameworks regulating citizenship entitlements and feeling
      ethnically discriminated were major sources of psycho-social strain. Except for
      sexually transmitted infections, participants rarely referred to communicable
      diseases as a concern. The perception that clinicians systematically prescribed
      painkillers discouraged health seeking and fostered self-medication. Participants
      felt that the medicalised, chemicalised, sexually liberal and accelerated culture
      of the host society damaged their own, and the local populations' health.
      CONCLUSION: Health systems bear a disproportionate responsibility in addressing
      health problems rooted in other sectors. Occupational and migration policies
      should be recognised explicitly as health policies. The mismatch between
      researchers' emphasis on communicable infections and the health concerns of Latin
      American migrants highlights the need for greater interaction between different
      forms of knowledge. In this process, the biomedical culture of reliance on
      pharmacological solutions should not remain unquestioned.

PMID- 26317782
TI  - Usefulness of Time-Point Serum Cortisol and ACTH Measurements for the Adjustment
      of Glucocorticoid Replacement in Adrenal Insufficiency.
AB  - BACKGROUND: Adjustment of daily hydrocortisone dose on clinical criteria lacks
      sensitivity for fine tuning. Long term hydrocortisone (HC) over-replacement may
      lead to increased morbidity and mortality in patients with adrenal insufficiency
      (AI). Biochemical criteria may help detecting over- or under-replacement but have
      been poorly evaluated. METHODS: Multicenter, institutional, pharmacokinetic study
      on ACTH and cortisol plasma profiles during HC replacement in 27 AI patients
      compared to 29 matched controls. All AI patients were administered HC thrice
      daily at doses of 6, 10 and 14 mg/m2/d. Blood samples were drawn hourly from
      0800h to 1900h. The main outcome measures were: i) plasma peak cortisol and
      cortisol area under the curve (AUC) in AI patients compared to controls, ii)
      correlations between cortisol AUC vs single-point cortisol or ACTH decrease from
      baseline (DeltaACTH) and iii) the predictive value of the two latters for
      obtaining AI patients' cortisol AUC in the control range. RESULTS: Cortisol peaks
      were observed 1h after each HC intake and a dose response was demonstrated for
      cortisol peak and cortisol AUC. The comparison of AI patients' cortisol AUC to
      controls showed that 81.5% AI patients receiving 6mg/m2/d were adequately
      replaced, whereas most patients receiving higher doses were over-replaced. The
      correlation coefficient between 1000h/1400h cortisol concentrations and 0800
      1900h cortisol AUC were 0.93/0.88 respectively, whereas the 0800-1200h DeltaACTH
      fairly correlated with 0800-1900h cortisol AUC (R = 0.57). ROC curve analysis
      indicated that the 1000h and 1400h cortisol concentrations best predicted over
      replacement. CONCLUSIONS: Patients receiving a 6mg/m2 hydrocortisone daily dose
      exhibited the most physiological daytime cortisol profile. Single point plasma
      cortisol correlated with daytime cortisol AUC in AI patients. Although
      hydrocortisone dose should be currently determined on clinical grounds, our data
      suggest that single point plasma cortisol may be an adjunct for further
      hydrocortisone dose adjustment in AI patients.

PMID- 26317784
TI  - Efficient Characterization of Parametric Uncertainty of Complex (Bio)chemical
      Networks.
AB  - Parametric uncertainty is a particularly challenging and relevant aspect of
      systems analysis in domains such as systems biology where, both for inference and
      for assessing prediction uncertainties, it is essential to characterize the
      system behavior globally in the parameter space. However, current methods based
      on local approximations or on Monte-Carlo sampling cope only insufficiently with
      high-dimensional parameter spaces associated with complex network models. Here,
      we propose an alternative deterministic methodology that relies on sparse
      polynomial approximations. We propose a deterministic computational interpolation
      scheme which identifies most significant expansion coefficients adaptively. We
      present its performance in kinetic model equations from computational systems
      biology with several hundred parameters and state variables, leading to numerical
      approximations of the parametric solution on the entire parameter space. The
      scheme is based on adaptive Smolyak interpolation of the parametric solution at
      judiciously and adaptively chosen points in parameter space. As Monte-Carlo
      sampling, it is "non-intrusive" and well-suited for massively parallel
      implementation, but affords higher convergence rates. This opens up new avenues
      for large-scale dynamic network analysis by enabling scaling for many
      applications, including parameter estimation, uncertainty quantification, and
      systems design. 

PMID- 26317785
TI  - When Is Rapid On-Site Evaluation Cost-Effective for Fine-Needle Aspiration
      Biopsy?
AB  - BACKGROUND: Rapid on-site evaluation (ROSE) can improve adequacy rates of fine
      needle aspiration biopsy (FNAB) but increases operational costs. The performance
      of ROSE relative to fixed sampling depends on many factors. It is not clear when
      ROSE is less costly than sampling with a fixed number of needle passes. The
      objective of this study was to determine the conditions under which ROSE is less
      costly than fixed sampling. METHODS: Cost comparison of sampling with and without
      ROSE using mathematical modeling. Models were based on a societal perspective and
      used a mechanistic, micro-costing approach. Sampling policies (ROSE, fixed) were
      compared using the difference in total expected costs per case. Scenarios were
      based on procedure complexity (palpation-guided or image-guided), adequacy rates
      (low, high) and sampling protocols (stopping criteria for ROSE and fixed
      sampling). One-way, probabilistic, and scenario-based sensitivity analysis was
      performed to determine which variables had the greatest influence on the cost
      difference. RESULTS: ROSE is favored relative to fixed sampling under the
      following conditions: (1) the cytologist is accurate, (2) the total variable cost
      ($/hr) is low, (3) fixed costs ($/procedure) are high, (4) the setup time is
      long, (5) the time between needle passes for ROSE is low, (6) when the per-pass
      adequacy rate is low, and (7) ROSE stops after observing one adequate sample. The
      model is most sensitive to variation in the fixed cost, the per-pass adequacy
      rate, and the time per needle pass with ROSE. CONCLUSIONS: Mathematical modeling
      can be used to predict the difference in cost between sampling with and without
      ROSE.

PMID- 26317783
TI  - Array CGH Analysis of Paired Blood and Tumor Samples from Patients with Sporadic
      Wilms Tumor.
AB  - Wilms tumor (WT), the most common cancer of the kidney in infants and children,
      has a complex etiology that is still poorly understood. Identification of genomic
      copy number variants (CNV) in tumor genomes provides a better understanding of
      cancer development which may be useful for diagnosis and therapeutic targets. In
      paired blood and tumor DNA samples from 14 patients with sporadic WT, analyzed by
      aCGH, 22% of chromosome abnormalities were novel. All constitutional alterations
      identified in blood were segmental (in 28.6% of patients) and were also present
      in the paired tumor samples. Two segmental gains (2p21 and 20q13.3) and one loss
      (19q13.31) present in blood had not been previously described in WT. We also
      describe, for the first time, a small, constitutive partial gain of 3p22.1
      comprising 2 exons of CTNNB1, a gene associated to WT. Among somatic alterations,
      novel structural chromosomal abnormalities were found, like gain of 19p13.3 and
      20p12.3, and losses of 2p16.1-p15, 4q32.5-q35.1, 4q35.2-q28.1 and 19p13.3.
      Candidate genes included in these regions might be constitutively (SIX3, SALL4)
      or somatically (NEK1, PIAS4, BMP2) operational in the development and progression
      of WT. To our knowledge this is the first report of CNV in paired blood and tumor
      samples in sporadic WT. 

PMID- 26317786
TI  - Associations of chronotype with social jetlag and behavioral problems in
      preschool children.
AB  - The timing, duration, and intensity of sleep are determined by the interaction
      between a sleep-wake-dependent homeostatic process and a sleep-wake-independent,
      intrinsic, clock-like circadian process. Chronotype represents individual
      differences in diurnal preferences, which are not only genetically determined but
      also influenced by social and environmental factors. Thus, the discrepancy
      between biological and social clocks, so-called "social jetlag", occurs.
      Chronotype, social jetlag, and the links between chronotype and behavioral
      problems are well documented in adults and adolescents. However, such studies on
      young children are limited. We conducted a survey of sleep and health for
      preschool children attending kindergarten or childcare centers in Wako, Okayama
      and Kurashiki cities, Japan, between May and July 2012. A total of 654 children
      aged 4-6 years (342 boys and 312 girls, with an average age of 4.7 years) were
      assessed using the Children's ChronoType Questionnaire and the Strength and
      Difficulties Questionnaire. Morning (M)-type, neither (N)-type and evening (E)
      type accounted for 36.2%, 54.0% and 9.8% of the participants, respectively. The
      weekday-to-weekend differences in midsleep time--originally proposed as the
      concept of social jetlag--were 11, 25 and 35 min for M-, N- and E-types,
      respectively. There was a negative correlation between chronotype and sleep
      period during weekdays (p < 0.001) and a positive correlation on weekends (p <
      0.001). The weekday-to-weekend difference in sleep period was 0.5 h for E-types,
      whereas there was no difference for M-types. Binomial logistic regression
      analyses were used to examine the links between chronotype and behavioral
      problems, adjusted for participants' sex, age, childcare programs and locations.
      Chronotype was significantly associated with hyperactivity/inattention: N-type
      (adjusted OR = 1.74, 95% CI = 1.03-2.95, p < 0.05) and E-type (adjusted OR =
      2.47, 95% CI = 1.18-5.20, p < 0.05). E-type was significantly associated with
      conduct problems (adjusted OR = 2.11, 95% CI = 1.03-4.31, p < 0.05) and peer
      problems (adjusted OR = 2.75, 95% CI = 1.18-6.44, p < 0.05). The results suggest
      that E-type children are vulnerable to higher social jetlag and more behavioral
      problems. The immature adjustment function of their endogenous circadian
      pacemakers may not be able to correct a small but significant social jetlag to
      synchronize with their social clocks. Furthermore, guidance based on
      chronobiological evidence is required for parents, teachers and health
      professionals to help children achieve optimal sleep and reduce behavioral
      problems.

PMID- 26317787
TI  - MicroRNA biomarker identification for pediatric acute myeloid leukemia based on a
      novel bioinformatics model.
AB  - Acute myeloid leukemia (AML) in children is a complex and heterogeneous disease.
      The identification of reliable and stable molecular biomarkers for diagnosis,
      especially early diagnosis, remains a significant therapeutic challenge. Aberrant
      microRNA expression could be used for cancer diagnosis and treatment selection.
      Here, we describe a novel bioinformatics model for the prediction of microRNA
      biomarkers for the diagnosis of paediatric AML based on computational functional
      analysis of the microRNA regulatory network substructure. microRNA-196b, microRNA
      155 and microRNA-25 were identified as putative diagnostic biomarkers for
      pediatric AML. Further systematic analysis confirmed the association of the
      predicted microRNAs with the leukemogenesis of AML. In vitro q-PCR experiments
      showed that microRNA-155 is significantly overexpressed in children with AML and
      microRNA-196b is significantly overexpressed in subgroups M4-M5 of the French
      American-British classification system. These results suggest that microRNA-155
      is a potential diagnostic biomarker for all subgroups of paediatric AML, whereas
      microRNA-196b is specific for subgroups M4-M5. 

PMID- 26317788
TI  - MicroRNA-494 inhibits cell proliferation and invasion of chondrosarcoma cells in
      vivo and in vitro by directly targeting SOX9.
AB  - Accumulating evidence indicates that dysregulation of miRNAs could contribute to
      tumor growth and metastasis of chondrosarcoma by infuencing cell proliferation
      and invasion. In the current study, we are interested to examine the role of
      miRNAs in the carcinogenesis and progression of chondrosarcoma. Here, using
      comparative miRNA profiling of tissues and cells of chondrosarcoma and cartilage,
      we identified miR-494 as a commonly downregulated miRNA in the tissues of
      patients with chondrosarcoma and chondrosarcoma cancer cell line, and
      upregulation of miR-494 could inhibit proliferation and invasion of
      chondrosarcoma cancer cells in vivo and in vitro. Moreover, our data demonstrated
      that SOX9, the essential regulator of the process of cartilage differentiation,
      was the direct target and functional mediator of miR-494 in chondrosarcoma cells.
      And downregulation of SOX9 could also inhibit migration and invasion of
      chondrosarcoma cells. In the last, we identified low expression of miR-494 was
      significantly correlated with poor overall survival and prognosis of
      chondrosarcoma patients. Thus, miR-494 may be a new common therapeutic target and
      prognosis biomarker for chondrosarcoma. 

PMID- 26317789
TI  - LDOC1 silenced by cigarette exposure and involved in oral neoplastic
      transformation.
AB  - Previously, we identified global epigenetic aberrations in smoking-associated
      oral squamous cell carcinoma (OSCC). We hypothesized that cigarette exposure
      triggers OSCC through alteration of the methylome of oral cells. Here we report
      that cigarette smoke condensate (CSC) significantly changes the genomic 5
      methyldeoxycytidine content and nuclear accumulation of DNA methyltransferase 1
      (DNMT1) and DNMT3A in human untransformed oral cells. By using integrated
      analysis of cDNA and methylation arrays of the smoking-associated dysplastic oral
      cell line and OSCC tumors, respectively, we identified four epigenetic targets-
      UCHL1, GPX3, LXN, and LDOC1--which may be silenced by cigarette. Results of
      quantitative methylation-specific PCR showed that among these four genes, LDOC1
      promoter was the most sensitive to CSC. LDOC1 promoter hypermethylation and gene
      silencing followed 3 weeks of CSC treatment. LDOC1 knockdown led to a
      proliferative response and acquired clonogenicity of untransformed oral cells.
      Immunohistochemistry showed that LDOC1 was downregulated in 53.3% (8/15) and
      57.1% (20/35) of premalignant oral tissues and early stage OSCCs, respectively,
      whereas 76.5% (13/17) of normal oral tissues showed high LDOC1 expression.
      Furthermore, the microarray data showed that LDOC1 expression had decreased in
      the lung tissues of current smokers compared with that in those of never smokers
      and had significantly decreased in the lung tumors of smokers compared with that
      in normal lung tissues. Our data suggest that CSC-induced promoter methylation
      may contribute to LDOC1 downregulation, thereby conferring oncogenic features to
      oral cells. These findings also imply a tumor suppressor role of LDOC1 in smoking
      related malignancies such as OSCC and lung cancer.

PMID- 26317790
TI  - IGFBP2 modulates the chemoresistant phenotype in esophageal adenocarcinoma.
AB  - Esophageal adenocarcinoma (EAC) patients commonly present with advanced stage
      disease and demonstrate resistance to therapy, with response rates below 40%.
      Understanding the molecular mechanisms of resistance is crucial for improvement
      of clinical outcomes. IGFBP2 is a member of the IGFBP family of proteins that has
      been reported to modulate both IGF and integrin signaling and is a mediator of
      cell growth, invasion and resistance in other tumor types. In this study, high
      IGFBP2 expression was observed in a subset of primary EACs and was found to be
      significantly higher in patients with shorter disease-free intervals as well as
      in treatment-resistant EACs as compared to chemonaive EACs. Modulation of IGFBP2
      expression in EAC cell lines promoted cell proliferation, migration and invasion,
      implicating a role in the metastatic potential of these cells. Additionally,
      knockdown of IGFBP2 sensitized EAC cells to cisplatin in a serum-dependent
      manner. Further in vitro exploration into this chemosensitization implicated both
      the AKT and ERK pathways. Silencing of IGFBP2 enhanced IGF1-induced immediate
      activation of AKT and reduced cisplatin-induced ERK activation. Addition of
      MEK1/2 (selumetinib or trametinib) or AKT (AKT Inhibitor VIII) inhibitors
      enhanced siIGFBP2-induced sensitization of EAC cells to cisplatin. These results
      suggest that targeted inhibition of IGFBP2 alone or together with either the MAPK
      or PI3K/AKT signaling pathway in IGFBP2-overexpressing EAC tumors may be an
      effective approach for sensitizing resistant EACs to standard neoadjuvant
      chemotherapy. 

PMID- 26317791
TI  - Opposed expression of IKKalpha: loss in keratinizing carcinomas and gain in non
      keratinizing carcinomas.
AB  - The functional role of IKKalpha in vivo is pretty complicated, largely due to its
      diverse functions through cell autonomous and non-autonomous manners. In
      addition, most of the studies on IKKalpha were derived from animal models,
      whether these findings hold true in human tumors remain unclear. Here we examined
      the expression of IKKalpha in nasopharyngeal carcinoma, which includes non
      keratinizing carcinoma and keratinizing squamous cell carcinoma, and lung
      squamous cell carcinoma with keratinization and non-keratinization. We
      demonstrated that IKKalpha expression was almost negative in keratinizing cancer
      and higher expression of IKKalpha was found in non-keratinizing cancer, and that
      IKKalpha expression correlated with cellular differentiation of tumors in non
      keratinizing nasopharyngeal carcinoma. These findings demonstrate that IKKalpha
      is diversely expressed in keratinizing and non-keratinizing carcinomas in the
      same type of cancer.

PMID- 26317792
TI  - Specificity protein (Sp) transcription factors and metformin regulate expression
      of the long non-coding RNA HULC.
AB  - Specificity protein 1 (Sp1) transcription factor (TF) regulates expression of
      long non-coding RNAs (lncRNAs) in hepatocellular carcinoma (HCC) cells. RNA
      interference (RNAi) studies showed that among several lncRNAs expressed in HepG2,
      SNU-449 and SK-Hep-1 cells, highly upregulated in liver cancer (HULC) was
      regulated not only by Sp1 but also Sp3 and Sp4 in the three cell lines. Knockdown
      of Sp transcription factors and HULC by RNAi showed that they play important
      roles in HCC cell proliferation, survival and migration. The relative
      contribution of Sp1, Sp3, Sp4 and HULC on these responses in HepG2, SNU-449 and
      SK-Hep-1 cells were cell context- and response-dependent. In the poorly
      differentiated SK-Hep-1 cells, knockdown of Sp1 or HULC resulted in genomic and
      morphological changes, indicating that Sp1 and Sp1-regulated HULC are important
      for maintaining the mesenchymal phenotype in this cell line. Genomic analysis
      showed an inverse correlation between expression of genes after knockdown of HULC
      and expression of those genes in liver tumors from patients. The antidiabetic
      drug metformin down-regulates Sp proteins in pancreatic cancer, and similar
      results including decreased HULC expression were observed in HepG2, SNU-449 and
      SK-Hep-1 cells treated with metformin, indicating that metformin and other
      antineoplastic agents that target Sp proteins may have clinical applications for
      HCC chemotherapy. 

PMID- 26317794
TI  - Enhanced nucleotide excision repair capacity in lung cancer cells by
      preconditioning with DNA-damaging agents.
AB  - The capacity of tumor cells for nucleotide excision repair (NER) is a major
      determinant of the efficacy of and resistance to DNA-damaging chemotherapeutics,
      such as cisplatin. Here, we demonstrate that using lesion-specific monoclonal
      antibodies, NER capacity is enhanced in human lung cancer cells after
      preconditioning with DNA-damaging agents. Preconditioning of cells with a
      nonlethal dose of UV radiation facilitated the kinetics of subsequent cisplatin
      repair and vice versa. Dual-incision assay confirmed that the enhanced NER
      capacity was sustained for 2 days. Checkpoint activation by ATR kinase and
      expression of NER factors were not altered significantly by the preconditioning,
      whereas association of XPA, the rate-limiting factor in NER, with chromatin was
      accelerated. In preconditioned cells, SIRT1 expression was increased, and this
      resulted in a decrease in acetylated XPA. Inhibition of SIRT1 abrogated the
      preconditioning-induced predominant XPA binding to DNA lesions. Taking these data
      together, we conclude that upregulated NER capacity in preconditioned lung cancer
      cells is caused partly by an increased level of SIRT1, which modulates XPA
      sensitivity to DNA damage. This study provides some insights into the molecular
      mechanism of chemoresistance through acquisition of enhanced DNA repair capacity
      in cancer cells. 

PMID- 26317793
TI  - Stemness and chemotherapeutic drug resistance induced by EIF5A2 overexpression in
      esophageal squamous cell carcinoma.
AB  - Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies
      of the digestive tract in East Asian countries. Multimodal therapies, including
      adjuvant chemotherapy and neo-adjuvant chemotherapy, have become more often used
      for patients with advanced ESCC. However, the chemotherapy effect is often
      limited by patients' drug resistance. This study demonstrated that EIF5A2
      (eukaryotic translation initiation factor 5A2) overexpression induced stemness
      and chemoresistance in ESCC cells. We showed that EIF5A2 overexpression in ESCC
      cells resulted in increased chemoresistance to 5-fluorouracil (5-FU), docetaxel
      and taxol. In contrast, shRNAs suppressing eIF5A2 increased tumor sensitivity to
      these chemotherapeutic drugs. In addition, EIF5A2 overexpression was correlated
      with a poorer overall survival in patients with ESCC who underwent taxane-based
      chemotherapy after esophagectomy (P < 0.05). Based on these results, we suggest
      that EIF5A2 could be a predictive biomarker for selecting appropriate chemo
      treatment for ESCC patients and EIF5A2 inhibitors might be considered as
      combination therapy to enhance chemosensitivity in patients with ESCC. 

PMID- 26317797
TI  - Correction: Irreversible Electroporation of Malignant Hepatic Tumors--Alterations
      in Venous Structures at Subacute Follow-Up and Evolution at Mid-Term Follow-Up.

PMID- 26317798
TI  - Sequence of Rubbing-Induced Molecular Segmental Reorientations in the Nanoscale
      Film Surface of a Brush Polymer Rod.
AB  - Poly(p-phenylene-3,6-bis(4-(n-butoxy)phenyloxy)pyromellitimide) (C4-PMDA-PDA PI),
      a well-defined model brush polymer composed of a rodlike polymer backbone with
      two bristles per repeat unit, was the first reported polyimide to align liquid
      crystals perpendicular to the rubbing direction at the rubbed film surface. In
      the present study, we used polarized infrared (IR) spectroscopy and 2D
      correlation analyses of the resulting IR spectra to study nanoscale films of C4
      PMDA-PDA PI rubbed at various rubbing densities. The results of these studies
      allowed us to establish the nature and sequence of the rubbing-induced segmental
      reorientations that occur in the polymer molecules at the film surface. The
      rubbing process was found to reorient the fully rodlike polymer backbones and the
      n-butyl bristle end groups such that they lay parallel to the rubbing direction.
      In contrast, rubbing caused the phenyloxy bristle units to reorient to a
      direction perpendicular to the rubbing direction. These reorientations of the
      polymer's main chain and bristles became more pronounced with increasing rubbing
      density, and the rubbing process had a greater effect on the polymer's main
      chains than on the bristles. The rubbing-induced reorientations of the polymer
      segments were found to follow the sequence PDA (phenyl ring), imide ring,
      phenyloxy unit, imide C-N bond, and n-butyl group. It was additionally evident
      that the rubbing process reorients the imide rings biaxially, that is, both along
      the rubbing direction and out of the plane. This biaxial reorientation was found
      to be accompanied by a biaxial reorientation of the bristles chemically bonded to
      the PMDA unit that includes the imide rings. In particular, increasing the
      rubbing density enhanced the out-of-plane reorientation of the imide rings. In
      contrast, no rubbing-induced inclination of the reoriented imide rings (i.e., the
      polymer's main chains) was detected. 

PMID- 26317795
TI  - Local production of the chemokines CCL5 and CXCL10 attracts CD8+ T lymphocytes
      into esophageal squamous cell carcinoma.
AB  - Esophageal squamous cell carcinoma (ESCC) is a very common malignant tumor with
      poor prognosis in China. Chemokines secreted by tumors are pivotal for the
      accumulation of CD8(+) T lymphocytes within malignant lesions in several types of
      cancers, but the exact mechanism underlying CD8(+) T lymphocyte homing is still
      unknown in ESCC. In this study, we revealed that, compared with marginal tissues,
      the expression of both chemokine (C-C motif) ligand 5 (CCL5) and (C-X-C motif)
      ligand 10 (CXCL10) was upregulated in ESCC tissues. CCL5 expression was
      positively associated with the overall survival of patients. Meanwhile, RT-PCR
      data showed that the expression of CCL5 and CXCL10 was positively correlated with
      the local expressions of the CD8(+) T lymphocyte markers (CD8 and Granzyme B) in
      tumor tissues. Correspondingly, CD8(+) T lymphocytes were more frequently CCR5-
      and CXCR3-positive in tumor than in peripheral blood. Transwell analysis showed
      both CCL5 and CXCL10 were important for the chemotactic movement of CD8(+) T
      lymphocytes. Our data indicate that CCL5 and CXCL10 serve as the key chemokines
      to recruit CD8(+) T lymphocytes into ESCC tissue and may play a role in patient
      survival.

PMID- 26317796
TI  - Coupling the modules of EMT and stemness: A tunable 'stemness window' model.
AB  - Metastasis of carcinoma involves migration of tumor cells to distant organs and
      initiate secondary tumors. Migration requires a complete or partial Epithelial-to
      Mesenchymal Transition (EMT), and tumor-initiation requires cells possessing
      stemness. Epithelial cells (E) undergoing a complete EMT to become mesenchymal
      (M) have been suggested to be more likely to possess stemness. However, recent
      studies suggest that stemness can also be associated with cells undergoing a
      partial EMT (hybrid E/M phenotype). Therefore, the correlation between EMT and
      stemness remains elusive. Here, using a theoretical framework that couples the
      core EMT and stemness modules (miR-200/ZEB and LIN28/let-7), we demonstrate that
      the positioning of 'stemness window' on the 'EMT axis' need not be universal;
      rather it can be fine-tuned. Particularly, we present OVOL as an example of a
      modulating factor that, due to its coupling with miR-200/ZEB/LIN28/let-7 circuit,
      fine-tunes the EMT-stemness interplay. Coupling OVOL can inhibit the stemness
      likelihood of M and elevate that of the hybrid E/M (partial EMT) phenotype,
      thereby pulling the 'stemness window' away from the M end of 'EMT axis'. Our
      results unify various apparently contradictory experimental findings regarding
      the interconnection between EMT and stemness, corroborate the emerging notion
      that partial EMT associates with stemness, and offer new testable predictions. 

PMID- 26317799
TI  - New distinct compartments in the G2 phase of the cell cycle defined by the levels
      of gammaH2AX.
AB  - Induction of DNA double strand breaks leads to phosphorylation and focus
      formation of H2AX. However, foci of phosphorylated H2AX (gammaH2AX) appear during
      DNA replication also in the absence of exogenously applied injury. We measured
      the amount and the number of foci of gammaH2AX in different phases of the cell
      cycle by flow cytometry, sorting and microscopy in 4 malignant B-lymphocyte cell
      lines. There were no detectable gammaH2AX and no gammaH2AX-foci in G1 cells in
      exponentially growing cells and cells treated with PARP inhibitor (PARPi) for 24
      h to create damage and reduce DNA repair. The amount of gammaH2AX increased
      immediately upon S phase entry, and about 10 and 30 gammaH2AX foci were found in
      mid-S phase control and PARPi-treated cells, respectively. The gammaH2AX-labeled
      damage caused by DNA replication was not fully repaired before entry into G2.
      Intriguingly, G2 cells populated a continuous distribution of gammaH2AX levels,
      from cells with a high content of gammaH2AX and the same number of foci as S
      phase cells (termed "G2H" compartment), to cells that there were almost negative
      and had about 2 foci (termed "G2L" compartment). EdU-labeling of S phase cells
      revealed that G2H was directly populated from S phase, while G2L was populated
      from G2H, but in control cells also directly from S phase. The length of G2H in
      particular increased after PARPi treatment, compatible with longer DNA-repair
      times. Our results show that cells repair replication-induced damage in G2H, and
      enter mitosis after a 2-3 h delay in G2L. 

PMID- 26317800
TI  - Effects of different concentrations of isoflurane pretreatment on respiratory
      mechanics, oxygenation and hemodynamics in LPS-induced acute respiratory distress
      syndrome model of juvenile piglets.
AB  - PURPOSE: This study was prospectively designed to investigate the effects of
      different concentrations of isoflurane (ISO) pretreatment on respiratory
      mechanics, oxygenation, and hemodynamics in lipopolysaccharide (LPS)-induced
      acute respiratory distress syndrome (ARDS) model of juvenile piglets. METHODS:
      Twenty-four piglets (9-14 kg, 5-6 weeks old) were randomly assigned to four
      groups (n = 6): LPS group, which was injected with LPS (20 MUg/kg) to induce
      ARDS; 0.5 ISO-LPS, 1.0 ISO-LPS, and 1.3 ISO-LPS groups, which were pretreated
      with 0.5, 1.0, and 1.3 minimum alveolar concentrations (MAC) ISO for 30 min
      before immediate LPS infusion, respectively. After establishment of ARDS,
      respiratory mechanism, oxygenation and hemodynamics parameters were measured at
      baseline, and 0, 1, 2, 3, and 4 hours after induction of ARDS. RESULTS: After
      induction of ARDS, there were increases in alveolar-arterial oxygen difference (A
      aDO2), oxygenation index (OI), mean airway pressure (MAP), dead space-to-tidal
      volume ratio, heart rate (HR), dP/dtmax, extravascular lung water index,
      pulmonary vascular permeability index, and PaCO2, and decreases in PaO2/FIO2,
      respiratory rate (RR), dynamic lung compliance (Cdyn), mean arterial blood
      pressure (MABP) and systemic vascular resistance (SVR) compared with baseline
      (P(time) < 0.05). Pretreatment with 1.0 and 1.3 MAC ISO alleviated changes in
      dP/dtmax and PaCO2 at ARDS 0-2 hours, SVR at 0-3 hours, PaO2/FIO2, RR, and MABP
      at 1-2 hours, HR at 2-3 hours, A-aDO2 at 3-4 hours, and OI at 4 hours (P(group) <
      0.05). CONCLUSION: Pretreatment with 1.0 and 1.3 MAC ISO had protective effects
      on respiratory mechanics, oxygenation, and hemodynamics in piglets with LPS
      induced ARDS.

PMID- 26317801
TI  - Clergy Views on a Good Versus a Poor Death: Ministry to the Terminally Ill.
AB  - BACKGROUND: Clergy are often important sources of guidance for patients and
      family members making medical decisions at the end-of-life (EOL). Previous
      research revealed spiritual support by religious communities led to more
      aggressive care at the EOL, particularly among minority patients. Understanding
      this phenomenon is important to help address disparities in EOL care. OBJECTIVE:
      The study objective was to explore and describe clergy perspectives regarding
      "good" versus "poor" death within the participant's spiritual tradition. METHODS:
      This was a qualitative, descriptive study. Community clergy from various
      spiritual backgrounds, geographical locations within the United States, and
      races/ethnicities were recruited. Participants included 35 clergy who
      participated in one-on-one interviews (N = 14) and two focus groups (N = 21).
      Semistructured interviews explored clergy viewpoints on factors related to a
      "good death." Principles of grounded theory were used to identify a final set of
      themes and subthemes. RESULTS: A good death was characterized by wholeness and
      certainty and emphasized being in relationship with God. Conversely, a "poor
      death" was characterized by separation, doubt, and isolation. Clergy identified
      four primary determinants of good versus poor death: dignity, preparedness,
      physical suffering, and community. Participants expressed appreciation for
      contextual factors that affect the death experience; some described a "middle
      death," or one that integrates both positive and negative elements. Location of
      death was not viewed as a significant contributing factor. CONCLUSIONS:
      Understanding clergy perspectives regarding quality of death can provide
      important insights to help improve EOL care, particularly for patients highly
      engaged with faith communities. These findings can inform initiatives to foster
      productive relationships between clergy, clinicians, and congregants and reduce
      health disparities.

PMID- 26317802
TI  - The physical demands of electrical utilities work in North America.
AB  - We assessed the physical demands associated with electrical utilities work in
      North America and how they influence the level of thermal and cardiovascular
      strain experienced. Three common job categories were monitored as they are
      normally performed in thirty-two electrical utility workers: (i) Ground Work (n =
      11), (ii) Bucket Work (n = 9), and (iii) Manual Pole Work (n = 12). Video
      analysis was performed to determine the proportion of the work monitoring period
      (duration: 187 +/- 104 min) spent at different levels of physical effort (i.e.,
      rest as well as light, moderate and heavy effort). Core and skin temperatures as
      well as heart rate were measured continuously. On average, workers spent 35.9 +/-
      15.9, 36.8 +/- 17.8, 24.7 +/- 12.8, and 2.6 +/- 3.3% of the work period at rest
      and performing work classified as light, moderate, and heavy physical effort,
      respectively. Moreover, a greater proportion of the work period was spent
      performing heavy work in Ground Work (1.6 +/- 1.4%) relative to Bucket Work (0.0
      +/- 0.0%; P<0.01) and in Manual Pole Climbing (5.5 +/- 3.6%) in comparison to
      both other work job (both P<=0.03). Furthermore, the proportion of time spent
      during work classified as heavy physical effort was positively correlated to the
      mean (r = 0.51, P<0.01) and peak (r = 0.42, P = 0.02) core temperatures achieved
      during the work period as well as the mean heart rate response (presented as a
      percentage of heart rate reserve; r = 0.40, P = 0.03). Finally, mean and peak
      core temperatures and mean heart rate responses increased from the first to the
      second half of the work shift; however, no differences in the proportion of the
      work spent at the different intensity classifications were observed. We show that
      Manual Pole Work is associated with greater levels of physical effort compared to
      Ground or Bucket Work. Moreover, we suggest that the proportion of time spent
      performing work classified as heavy physical exertion is related to the level of
      thermal and cardiovascular strain experienced and that workers may not be
      employing self-pacing as a strategy to manage their level of physiological
      strain.

PMID- 26317804
TI  - In Vivo Capture of Circulating Tumor Cells Based on Transfusion with a Vein
      Indwelling Needle.
AB  - Detection of circulating tumor cells (CTCs) could be used as a "liquid biopsy"
      for tracking the spread of cancer. In vitro detection methods based on blood
      sampling and in vitro CTC capture often suffer from the small sampling volume and
      sampling error. Here, the in vivo capture of CTCs based on transfusion with a
      surface-modified vein indwelling needle is proposed. When the needle was applied
      to transfusion in the vein, the simultaneous capture of CTCs was performed. To
      investigate the actual capture efficiency of the in vivo capture method, labeled
      MCF-7 cells were directly injected into the veins of rabbits, wild type mice, and
      nude mice and could be successfully captured. Two of 5 MCF-7 cells injected into
      the veins of nude mice were successfully captured. To investigate the CTC capture
      of mouse tumor model and compare with the in vitro method, mice were subcutaneous
      inoculated with metastatic 4T1 cells. Seven and 21 days after inoculation, CTCs
      were captured for the first time using in vivo and in vitro methods,
      respectively. This predicted that the in vivo method could be more suitable for
      use of early diagnosis of cancer than the in vitro method. As CTC capture can be
      performed at the same time as transfusion and does not cause further bodily harm,
      it would be easily accepted by patients. This efficient, simple, and less
      damaging method involving the use of a vein indwelling needle could be
      popularized easily in the clinic. 

PMID- 26317803
TI  - Generation of SNCA Cell Models Using Zinc Finger Nuclease (ZFN) Technology for
      Efficient High-Throughput Drug Screening.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by
      loss of dopaminergic neurons of the substantia nigra. The hallmark of PD is the
      appearance of neuronal protein aggregations known as Lewy bodies and Lewy
      neurites, of which alpha-synuclein forms a major component. Familial PD is rare
      and is associated with missense mutations of the SNCA gene or increases in gene
      copy number resulting in SNCA overexpression. This suggests that lowering SNCA
      expression could be therapeutic for PD. Supporting this hypothesis, SNCA
      reduction was neuroprotective in cell line and rodent PD models. We developed
      novel cell lines expressing SNCA fused to the reporter genes luciferase (luc) or
      GFP with the objective to enable high-throughput compound screening (HTS) for
      small molecules that can lower SNCA expression. Because SNCA expression is likely
      regulated by far-upstream elements (including the NACP-REP1 located at 8852 bp
      upstream of the transcription site), we employed zinc finger nuclease (ZFN)
      genome editing to insert reporter genes in-frame downstream of the SNCA gene in
      order to retain native SNCA expression control. This ensured full retention of
      known and unknown up- and downstream genetic elements controlling SNCA
      expression. Treatment of cells with the histone deacetylase inhibitor valproic
      acid (VPA) resulted in significantly increased SNCA-luc and SNCA-GFP expression
      supporting the use of our cell lines for identifying small molecules altering
      complex modes of expression control. Cells expressing SNCA-luc treated with a
      luciferase inhibitor or SNCA siRNA resulted in Z'-scores >= 0.75, suggesting the
      suitability of these cell lines for use in HTS. This study presents a novel use
      of genome editing for the creation of cell lines expressing alpha-synuclein
      fusion constructs entirely under native expression control. These cell lines are
      well suited for HTS for compounds that lower SNCA expression directly or by
      acting at long-range sites to the SNCA promoter and 5'-UTR. 

PMID- 26317805
TI  - Enhancement of BACE1 Activity by p25/Cdk5-Mediated Phosphorylation in Alzheimer's
      Disease.
AB  - The activity of beta-site amyloid precursor protein (APP) cleaving enzyme 1
      (BACE1) is elevated during aging and in sporadic Alzheimer's disease (AD), but
      the underlying mechanisms of this change are not well understood. p25/Cyclin
      dependent kinase 5 (Cdk5) has been implicated in the pathogenesis of several
      neurodegenerative diseases, including AD. Here, we describe a potential mechanism
      by which BACE activity is increased in AD brains. First, we show that BACE1 is
      phosphorylated by the p25/Cdk5 complex at Thr252 and that this phosphorylation
      increases BACE1 activity. Then, we demonstrate that the level of phospho-BACE1 is
      increased in the brains of AD patients and in mammalian cells and transgenic mice
      that overexpress p25. Furthermore, the fraction of p25 prepared from iodixanol
      gradient centrifugation was unexpectedly protected by protease digestion,
      suggesting that p25/Cdk5-mediated BACE1 phosphorylation may occur in the lumen.
      These results reveal a link between p25 and BACE1 in AD brains and suggest that
      upregulated Cdk5 activation by p25 accelerates AD pathogenesis by enhancing BACE1
      activity via phosphorylation. 

PMID- 26317806
TI  - Evidence of Active Pro-Fibrotic Response in Blood of Patients with Cirrhosis.
AB  - The role of systemic immunity in the pathogenesis of cirrhosis is not fully
      understood. Analysis of transcriptomic profiles in blood is an easy approach to
      obtain a wide picture of immune response at the systemic level. We studied gene
      expression profiles in blood from thirty cirrhotic patients and compared them
      against those of eight healthy volunteers. Most of our patients were male [n =
      21, 70%] in their middle ages [57.4 +/- 6.8 yr]. Alcohol abuse was the most
      frequent cause of cirrhosis (n = 22, 73%). Eleven patients had hepatocellular
      carcinoma (36.7%). Eight patients suffered from hepatitis C virus infection
      (26.7%). We found a signature constituted by 3402 genes which were differentially
      expressed in patients compared to controls (2802 over-expressed and 600 under
      expressed). Evaluation of this signature evidenced the existence of an active pro
      fibrotic transcriptomic program in the cirrhotic patients, involving the [extra
      cellular matrix (ECM)-receptor interaction] & [TGF-beta signaling] pathways along
      with the [Cell adhesion molecules] pathway. This program coexists with
      alterations in pathways participating in [Glycine, serine and threonine
      metabolism], [Phenylalanine metabolism], [Tyrosine metabolism], [ABC
      transporters], [Purine metabolism], [Arachidonic acid metabolism]. In
      consequence, our results evidence the co-existence in blood of a genomic program
      mediating pro-fibrotic mechanisms and metabolic alterations in advanced
      cirrhosis. Monitoring expression levels of the genes involved in these programs
      could be of interest for predicting / monitoring cirrhosis evolution. These genes
      could constitute therapeutic targets in this disease. 

PMID- 26317808
TI  - Application of N-Butyl Cyanoacrylate to Split-Thickness Skin Grafts in Rats: An
      Experimental Study.
AB  - Skin grafts are a standard option for closing skin defects that cannot be closed
      primarily. A split -thickness skin graft entirely transfers the epidermis and a
      part of the dermal layer to the wound site. Using conventional techniques, the
      skin graft is fixed to the wound using sutures and kept closed for 3 to 7 days
      with a pressed bolster dressing. Continued care includes applying routine graft
      dressings after the bolster dressing has been removed. The use of fibrin glue and
      cyanoacrylate derivatives-which shortens the duration of surgery and improves
      graft fixation to the recipient bed-has become widespread. However, applying
      fibrin glue during skin graft surgery is limited because there are considerable
      disadvantages in terms of preparation and cost. Many studies have been conducted
      on the use of cyanoacrylate derivatives during skin grafting; however, few
      reports have investigated the effects of cyanoacrylate derivatives on skin graft
      survival and related histopathologic changes.In this study, the authors used n
      butyl cyanoacrylate to prepare split-thickness skin grafts that were subsequently
      applied to Wistar albino rats, and the authors evaluated the results both
      histopathologically and macroscopically. The authors also statistically analyzed
      the effects of graft fixation according to surgical duration. The findings of
      authors suggest that n-butyl cyanoacrylate can be safely applied during split
      thickness skin graft surgery because it significantly reduces surgical duration,
      demonstrates substantial advantages in terms of graft fixation and monitoring,
      and, most importantly, demonstrates no notable disadvantages in comparison with
      conventional methods. 

PMID- 26317807
TI  - Evolving role of radiolabeled particles in detecting infection and inflammation,
      preliminary data with 99mTc-phytate in rats.
AB  - PURPOSE: The aim of this study was to evaluate the ability of phytate
      radiolabeled with technetium-99m (Tc-phytate) to identify inflammatory processes.
      MATERIALS AND METHODS: Radiolabeling efficiency analyses were carried out by thin
      layer chromatography on silica gel strips, yielding a radiochemical purity of
      92%. In addition, the partition coefficient of Tc-phytate, obtained in a mixture
      of n-octanol/water (1 : 1), showed hydrophilic features of the
      radiopharmaceutical. After Tc-phytate was administered into the tail vein of
      healthy and inflammation focus-bearing rats, induced, in the right tight, by
      zymosan suspension at 5% (w/v), blood clearance evaluation was performed and
      showed a short plasma half-life (2.7 min). In the inflammation focus-bearing
      rats, Tc-phytate scintigraphic images were obtained at 2, 4, and 8 h after
      radiotracer injection. RESULTS: A significant radiopharmaceutical uptake was
      found in mononuclear phagocyte system organs (liver and spleen) and in the
      inflammation focus (compared with contralateral muscle). Histopathological
      analysis showed an intense mononuclear infiltration in the inflamed muscle,
      suggesting that macrophages may be responsible for the greater radiotracer uptake
      in the inflamed site. Furthermore, the target-to-nontarget ratio (%ID/g of
      inflamed muscle-to-%ID/g of control muscle ratio) obtained by scintigraphic
      images performed at 2 h after the radiotracer injection was 10.24+/-3.49,
      remaining without any significant difference at 4 and 8 h. CONCLUSION:
      Inflammation focus was evident in the scintigraphic images from 2 to 8 h after Tc
      phytate administration, suggesting that this radiopharmaceutical could be a
      potential alternative to identify inflamed regions.

PMID- 26317809
TI  - Repair of a Large Surgical Defect Involving the External Auditory Canal and
      Sideburn.

PMID- 26317810
TI  - Prelaminated and Prefolded Paramedian Forehead Flap for Loss of the Nasal Tip.

PMID- 26317811
TI  - Cutaneous Sarcoidosis Successfully Treated With Intralesional 5-Fluorouracil.

PMID- 26317812
TI  - A pilot study of chest tube versus pigtail catheter drainage of acute hemothorax
      in swine.
AB  - BACKGROUND: Evacuation of traumatic hemothorax (HTx) is typically accomplished
      with large-bore (28-40 Fr) chest tubes, often resulting in patient discomfort.
      Management of HTx with smaller (14 Fr) pigtail catheters has not been widely
      adopted because of concerns about tube occlusion and blood evacuation rates. We
      compared pigtail catheters with chest tubes for the drainage of acute HTx in a
      swine model. METHODS: Six Yorkshire cross-bred swine (44-54 kg) were
      anesthetized, instrumented, and mechanically ventilated. A 32 Fr chest tube was
      placed in one randomly assigned hemithorax; a 14 Fr pigtail catheter was placed
      in the other. Each was connected to a chest drainage system at -20 cm H2O suction
      and clamped. Over 15 minutes, 1,500 mL of arterial blood was withdrawn via
      femoral artery catheters. Seven hundred fifty milliliters of the withdrawn blood
      was instilled into each pleural space, and fluid resuscitation with colloid was
      initiated. The chest drains were then unclamped. Output from each drain was
      measured every minute for 5 minutes and then every 5 minutes for 40 minutes. The
      swine were euthanized, and thoracotomies were performed to quantify the volume of
      blood remaining in each pleural space and to examine the position of each tube.
      RESULTS: Blood drainage was more rapid from the chest tube during the first 3
      minutes compared with the pigtail catheter (348 +/- 109 mL/min vs. 176 +/- 53
      mL/min), but this difference was not statistically significant (p = 0.19).
      Thereafter, the rates of drainage between the two tubes were not substantially
      different. The chest tube drained a higher total percentage of the blood from the
      chest (87.3% vs. 70.3%), but this difference did not reach statistical
      significance (p = 0.21). CONCLUSION: We found no statistically significant
      difference in the volume of blood drained by a 14 Fr pigtail catheter compared
      with a 32 Fr chest tube.

PMID- 26317813
TI  - Role of computed tomography angiography in the management of Zone II penetrating
      neck trauma in patients with clinical hard signs.
AB  - BACKGROUND: The Western Trauma Association (WTA) describes the management of Zone
      2 penetrating neck trauma (PNT) and recommends neck exploration (NE) for patients
      with clinical hard signs (HS). We hypothesize that in stable patients with HS,
      the management of PNT augmented by computed tomography angiography (CTA) results
      in fewer negative NE results. METHODS: This was a 4-year retrospective review of
      adult patients with Zone 2 PNT at a Level I trauma center. Stable patients with
      WTA-defined HS (airway compromise, massive subcutaneous emphysema/air bubbling
      through wound, expanding/pulsatile hematoma, active bleeding, shock, focal
      neurologic deficit, and hematemesis) who underwent CTA instead of emergent
      exploration were identified. Sensitivity, specificity, positive predictive value,
      and negative predictive value for CTA were calculated. A comparison was made
      between the rates of negative NE results in patients with HS who received a CTA
      versus the rate that would have occurred in the same patients if the WTA
      algorithm had been followed. Missed injury rates were also compared. RESULTS: Of
      183 PNT patients, 23 had HS and underwent CTA. Of the 23, 5 had a positive CTA
      findings and underwent NE, while 17 had a negative CTA findings and did not
      require NE. There was one false-negative in a patient who developed an expanding
      hematoma following negative neck CTA finding. Sensitivity, specificity, positive
      predictive value, and negative predictive value for CTA in the presence of HS
      were found to be 83%, 100%, 100%, and 94%, respectively. The addition of CTA to
      the WTA algorithm for this patient group significantly decreased the rate of
      negative NE (0 of 23 vs. 18 of 23, p < 0.001) without a significant increase in
      the rate of missed injury (1 of 23 vs. 0 of 23, p = 0.323). The use of CTA
      prevented 17 unnecessary NEs. CONCLUSION: CTA addition to the management of
      hemodynamically stable patients with HS in PNT significantly decreased the rate
      of negative NE result without increasing missed injury rate. Prospective study of
      CTA addition to the WTA algorithm is needed. LEVEL OF EVIDENCE: Care
      management/therapeutic study, level IV.

PMID- 26317814
TI  - Seasonal variations in posttraumatic wound infections after open extremity
      fractures.
AB  - BACKGROUND: The vast majority of the orthopedic trauma literature has dealt with
      risk of infection as a function of time to debridement and severity of open
      fracture. The goal of this analysis was to determine if either the incidence or
      causative organism of posttraumatic infection varies with the season in which the
      open fracture occurred. No such study has been previously published. METHODS:
      This is a retrospective chart review of all skeletally mature patients sustaining
      an open fracture of either the upper or the lower extremity long bones from 2007
      to 2012. Charts were reviewed to extract information regarding date of injury,
      Gustilo-Anderson grade of open fracture, Injury Severity Score (ISS), time to
      surgical debridement, any posttraumatic wound infection (deep or superficial),
      and the causative organisms. Patients were placed into one of four groups based
      on the time of year: spring (March to May), summer (June to August), fall
      (September to November), and winter (December to February). Patients were
      excluded if they were skeletally immature, smokers, or also diagnosed with a
      condition that would increase risk of infection. Statistical analysis was
      performed to assess whether any observed differences were of significance.
      RESULTS: All four groups were similar with respect to Gustilo grade, ISS, and
      time to surgical debridement. A total of 1,128 open fractures were treated
      between 2007 and 2012. There were 58 total infections for an overall incidence of
      4.3%. The incidence of infection based on season was 6.0% for spring, 4.9% for
      summer, 2.8% for fall, and 3.6% for winter (p < 0.05). The incidence of infection
      was 5.5% for spring and summer combined and 3.9% for winter and fall combined (p
      < 0.05). Gram-positive organisms were more prevalent in the spring and summer
      seasons (p < 0.05). Although gram-negative organisms were cultured more commonly
      in the fall and winter seasons (52%) compared with the spring and summer seasons
      (36%), they were evenly distributed with gram-positive organisms during the
      winter and fall. CONCLUSION: A seasonal variation exists regarding the incidence
      of infection and causative organisms for posttraumatic wound infection following
      open extremity fractures. The incidence of infection is significantly higher in
      the spring and summer months with a preponderance of gram-positive organisms.
      Patients with infection after injuries sustained in the fall and winter months
      are more likely to have a Gustilo Grade 3 injury and gram-negative bacteria as
      the causative organism. LEVEL OF EVIDENCE: Epidemiologic study, level III.

PMID- 26317816
TI  - Witnessed aspiration in trauma: Frequent occurrence, rare morbidity--A
      prospective analysis.
AB  - BACKGROUND: Aspiration events (AEs) are a well-recognized complication in trauma
      patients and have traditionally been considered a risk factor for pneumonia.
      Despite this, there is no consensus on the incidence or clinical significance of
      AE in the trauma population. METHODS: All patients admitted as trauma team
      activations at our Level I trauma center who were intubated in the field or on
      arrival from September 2013 to August 2014 were prospectively collected. Field
      and admission data including witnessed AEs were analyzed. Additional hospital
      data included imaging, associated injuries, laboratory, and clinical data. Early
      respiratory failure, pneumonia, and hospital mortality were collected. RESULTS:
      During the study period, 228 patients met inclusion criteria. Median age was 35.5
      years, and Injury Severity Score (ISS) was 21.0. Overall, 58 patients (25.4%) had
      witnessed AEs. Patients with AE had significantly higher ISS (26.0 vs. 17.0, p =
      0.027) and lower Glasgow Coma Scale (GCS) score on admission (median, 4.0 vs.
      7.0; p = 0.003), despite similar field GCS score (p = 0.946). Body mass index
      (median, 27.2 vs. 26.2; p = 0.374) and intoxication rates (86.2% vs. 83.5%, p =
      0.835) were similar between groups. Early pneumonia and respiratory failure were
      rare in all patients and were not higher in those with AE. Although mortality was
      higher after AE in patients who died directly after admission (51.7% vs. 30.0%, p
      = 0.004), in patients who survived to intensive care unit admission, there was no
      longer a difference between groups and aspiration was not an independent
      predictor of mortality (p = 0.107) on multivariable regression analysis.
      CONCLUSION: The rate of aspiration in trauma is high and more likely to occur in
      patients with increased injury burden or depressed GCS score. In patients who
      survive past admission, early pneumonia rates are similar, regardless of AE.
      These data suggest that aspiration is a marker of severe illness and is
      associated with but not an independent predictor of mortality. LEVEL OF EVIDENCE:
      Prognostic/epidemiologic study, level III.

PMID- 26317815
TI  - The tissue factor pathway mediates both activation of coagulation and
      coagulopathy after injury.
AB  - BACKGROUND: The initiation of coagulation in trauma is thought to originate from
      exposed tissue factor (TF); recent data have led to the alternative hypothesis
      that damage-associated molecular patterns may contribute to postinjury
      coagulation. In acute traumatic coagulopathy, aberrant coagulation is mediated
      via the activated protein C (aPC) pathway; the upstream regulators of this
      process and its relation to TF remain uncharacterized. To examine the role of the
      TF pathway in mediating acute traumatic coagulopathy, we used specific antibody
      blockades in an established murine model of traumatic hemorrhagic shock,
      hypothesizing that both coagulation activation after injury and aPC-mediated
      coagulopathy are driven by TF via thrombin. METHODS: Mice underwent an
      established model of trauma and hemorrhage and were subjected to either sham
      (vascular cannulation) or trauma-hemorrhage (cannulation, laparotomy, shock to
      mean arterial pressure of 35 mm Hg); they were monitored for 60 minutes before
      sacrifice. Mice in each group were pretreated with either targeted anti-TF
      antibody to block the TF pathway or hirudin for specific blockade of thrombin.
      Plasma was assayed for thrombin-antithrombin (TAT) and aPC by enzyme-linked
      immunosorbent assay. RESULTS: Compared with controls, trauma-hemorrhage mice
      treated with anti-TF antibody had significantly reduced levels of TAT (2.3 ng/mL
      vs. 5.7 ng/mL, p = 0.016) and corresponding decreases in aPC (16.3 ng/mL vs. 31.6
      ng/mL, p = 0.034), with reductions to levels seen in sham mice. Direct inhibition
      of thrombin yielded similar results, with reduction in aPC to levels below those
      seen in sham mice. CONCLUSION: In this study, blockade of the TF pathway led to
      the attenuation of both thrombin production and aPC activation observed in
      traumatic shock. Specific thrombin inhibition achieved similar results,
      indicating that aPC-related coagulopathy is mediated via thrombin activated by
      the TF pathway. The near-complete blockade of TAT and aPC observed in this model
      argues for a dominant role of the TF-thrombin pathway in both coagulation
      activation after injury and traumatic coagulopathy.

PMID- 26317817
TI  - Early tranexamic acid administration: A protective effect on gut barrier function
      following ischemia/reperfusion injury.
AB  - BACKGROUND: The mucus barrier is a critical component of the gut barrier and may
      be disrupted by pancreatic enzymes following trauma/hemorrhagic shock (T/HS).
      Luminal strategies against pancreatic enzyme activation or contact with the
      intestine are protective of the mucus layer and gut barrier integrity following
      T/HS. There is increasing evidence the use of tranexamic acid (TA) attenuates
      inflammatory responses in cardiac surgery and is readily absorbed from the gut.
      We therefore postulated that systemic administration of TA would attenuate mucus
      degradation and gut barrier failure following T/HS. This was studied in an in
      vitro model. METHODS: Confluent monolayers of HT29-MTX (mucus-producing clone)
      and Caco-2 cocultures were exposed to 90 minutes of hypoxia followed by
      reoxygenation (H/R), luminal trypsin (5 MUM), or both treatment groups. In a
      subset of experiments, TA (40 MUM or 150 MUM) was added to the basal chamber
      (systemic side) of intestinal cell cultures immediately following the hypoxic
      period. Mucus barrier function was indexed by rheologic measurement of both mucus
      thickness and viscosity (G', dyne/cm) and oxidant stress. Intestinal cell barrier
      integrity was indexed by transepithelial electrical resistance, permeability to
      fluorescein isothiocyanate-dextran, and apoptosis by flow cytometry. RESULTS:
      Exposure to both trypsin and H/R of Caco-2/HT29-MTX cocultures led to the most
      severe effect on mucus barrier function. Administration of TA immediately
      following hypoxia abrogated the effects noted on mucus barrier function. The
      epithelial barrier was also most severely impacted by both trypsin and H/R.
      Addition of TA after the hypoxic event was shown to be protective. CONCLUSION:
      Intestinal mucus physiochemical properties and intestinal barrier function were
      most severely impacted by exposure to both trypsin (concentration related) and
      H/R. The "systemic" administration of TA immediately after the hypoxic period was
      protective and suggests an additional role for early administration of TA in
      trauma patients in shock.

PMID- 26317818
TI  - Emergent operation for isolated severe traumatic brain injury: Does time matter?
AB  - BACKGROUND: It remains unclear whether the timing of neurosurgical intervention
      impacts the outcome of patients with isolated severe traumatic brain injury
      (TBI). We hypothesized that a shorter time between emergency department (ED)
      admission to neurosurgical intervention would be associated with a significantly
      higher rate of patient survival. METHODS: Our institutional trauma registry was
      queried for patients (2003-2013) who required an emergent neurosurgical
      intervention (craniotomy, craniectomy) for TBI within 300 minutes after the ED
      admission. We included patients with altered mental status upon presentation in
      the ED (Glasgow Coma Scale [GCS] score < 9). Patients with associated severe
      injuries (Abbreviated Injury Scale [AIS] score >= 2) in other body regions were
      excluded. In-hospital mortality of patients who underwent surgery in less than
      200 minutes (early group) was compared with those who underwent surgery in 200
      minutes or longer (late group) using univariate and multivariate analyses.
      RESULTS: A total of 161 patients were identified during the study time frame.
      Head computed tomographic scan demonstrated subdural hematoma in 85.8%,
      subarachnoid hemorrhage in 55.5%, and equal numbers of epidural hematoma and
      intraparenchymal hemorrhage in 22.6%. Median time between ED admission and
      neurosurgical intervention was 133 minutes. In univariate analysis, a
      significantly lower in-hospital mortality rate was identified in the early group
      (34.5% vs. 59.1%, p = 0.03). After adjusting for clinically important covariates
      in a logistic regression model, early neurosurgical intervention was
      significantly associated with a higher odds of patient survival (odds ratio,
      7.41; 95% confidence interval, 1.66-32.98; p = 0.009). CONCLUSION: Our data
      suggest that the survival rate of isolated severe TBI patients who required an
      emergent neurosurgical intervention could be time dependent. These patients might
      benefit from expedited process (computed tomographic scan, neurosurgical
      consultation, etc.) to shorten the time to surgical intervention. LEVEL OF
      EVIDENCE: Prognostic study, level IV.

PMID- 26317819
TI  - Heparin versus enoxaparin for prevention of venous thromboembolism after trauma:
      A randomized noninferiority trial.
AB  - BACKGROUND: Research comparing enoxaparin with unfractionated heparin (UFH) given
      every 12 hours for venous thromboembolism (VTE) prophylaxis after trauma
      overlooks original recommendations that UFH be given every 8 hours. We conducted
      a prospective, randomized, noninferiority trial comparing UFH every 8 hours and
      standard enoxaparin every 12 hours. We hypothesized that the incidence of VTE in
      trauma patients receiving UFH every 8 hours would be no more than 10% higher than
      that in patients receiving enoxaparin every 12 hours. METHODS: Trauma patients
      who met criteria for VTE prophylaxis at a Level I trauma center were randomly
      assigned to 5,000-U UFH every 8 hours or 30-mg enoxaparin every 12 hours between
      November 2012 and September 2014. Surveillance duplex ultrasound was performed
      twice weekly on intensive care unit patients and weekly on ward patients. Primary
      end points were deep vein thrombosis diagnosed by duplex ultrasound and pulmonary
      embolism diagnosed by computed tomography angiography. RESULTS: Of 495 randomized
      patients, 220 received UFH and 216 received enoxaparin for analysis. Overall, 105
      in the UFH group and 103 in the enoxaparin group underwent VTE surveillance or
      diagnostic testing. In the analysis of randomized patients who received
      treatment, UFH was noninferior compared with enoxaparin (absolute VTE risk
      difference, 3.1%; 95% confidence interval, -1.6% to 7.7%; p = 0.196); however, in
      the screening ultrasound group, the noninferiority of UFH was inconclusive
      (absolute VTE risk difference, 6.5%; 95% confidence interval, -2.9% to 15.8%; p =
      0.179). The two treatments did not differ with regard to adverse events. The
      pharmaceutical cost for the regimen of UFH ($2,809) was nearly 20-fold lower than
      that for enoxaparin ($54,138). CONCLUSION: A regimen of UFH every 8 hours may be
      noninferior to enoxaparin every 12 hours for the prevention of VTE following
      trauma. Given UFH's cost advantage, the use of UFH for VTE prophylaxis may offer
      greater value. LEVEL OF EVIDENCE: Therapeutic/care management study, level II.

PMID- 26317823
TI  - Chemoselective C(sp(3) )-H Activations for the Preparation of Condensed N
      Heterocycles.

PMID- 26317826
TI  - Benchmark Thermochemistry for Biologically Relevant Adenine and Cytosine. A
      Combined Experimental and Theoretical Study.
AB  - The thermochemical properties available in the literature for adenine and
      cytosine are in disarray. A new condensed phase standard (p degrees  = 0.1 MPa)
      molar enthalpy of formation at T = 298.15 K was measured by using combustion
      calorimetry. New molar enthalpies of sublimation were derived from the
      temperature dependence of vapor pressure measured by transpiration and by the
      quarz-crystal microbalance technique. The heat capacities of crystalline adenine
      and cytosine were measured by temperature-modulated DSC. Thermodynamic data on
      adenine and cytosine available in the literature were collected, evaluated, and
      combined with our experimental results. Thus, the evaluated collection of data
      together with the new experimental results reported here has helped to resolve
      contradictions in the available enthalpies of formation. A set of reliable
      thermochemical data is recommended for adenine and cytosine for further
      thermochemical calculations. Quantum-chemical calculations of the gas phase molar
      enthalpies of formation of adenine and cytosine have been performed by using the
      G4 method and results were in excellent agreement with the recommended
      experimental data. The standard molar entropies of formation and the standard
      molar Gibbs functions of formation in crystal and gas state have been calculated.
      Experimental vapor-pressure data measured in this work were used to estimate pure
      component PC-SAFT parameters. This allowed modeling solubility of adenine and
      cytosine in water over the temperature interval 278-310 K. 

PMID- 26317827
TI  - Development of genu valgum after removal of osteochondromas from the proximal
      tibia.
AB  - Genu valgum is a well-documented deformity secondary to hereditary multiple
      exostoses about the knee. Post-traumatic tibia valgus is also a well-described
      phenomenon that occurs in children who sustain an incomplete fracture of the
      proximal tibia. The finding is considered to be secondary to asymmetric blood
      flow to the proximal tibial physis. The existing literature only describes genu
      valgum as a sequela of the hereditary multiple exostoses disorder itself and does
      not address genu valgum occurring as a postoperative consequence of mass
      excision. In this paper, we report on three pediatric patients who developed
      unilateral genu valgum after removal of osteochondromas from the medial proximal
      tibia. Chart and radiographic data were retrospectively reviewed for a series of
      three patients. Three patients developed genu valgum after medial proximal tibial
      osteochondroma excision. The maximum tibiofemoral angle varied from 17 to 23
      degrees . One case resolved spontaneously with observation, one was addressed
      surgically with guided growth correction, and another was advised to undergo
      operative correction, but declined. We conclude that genu valgum can arise
      secondary to osteochondroma excision when the mass is resected near the proximal
      tibial physis. Surgeons should counsel patients on the possibility of
      postoperative angular growth deformity and monitor closely for its development. 

PMID- 26317828
TI  - Changing outcomes in acute liver failure: Can we transplant only the ones who
      really need it?

PMID- 26317830
TI  - Dual Exchange in PCN-333: A Facile Strategy to Chemically Robust Mesoporous
      Chromium Metal-Organic Framework with Functional Groups.
AB  - A facile preparation of a mesoporous Cr-MOF, PCN-333(Cr) with functional group,
      has been demonstrated through a dual exchange strategy, involving a sequential
      ligand exchange and metal metathesis process. After optimization of the exchange
      system, the functionalized PCN-333(Cr), N3-PCN-333(Cr) shows well maintained
      crystallinity, porosity, as well as much improved chemical stability. Because of
      the exceptionally large pores (~5.5 nm) in PCN-333(Cr), a secondary functional
      moiety, Zn-TEPP with a size of 18 A * 18 A, has been successfully clicked into
      the framework. In this article, we have also analyzed kinetics and thermodynamics
      during dual exchange process, showing our attempts to interpret the exchange
      event in the PCN-333. Our findings not only provide a highly stable mesoporous Cr
      MOF platform for expanding MOF-based applications, but also suggest a route to
      functionalized Cr-MOF which may have not been achievable through conventional
      approaches. 

PMID- 26317829
TI  - Inflow/Outflow Boundary Conditions for Particle-Based Blood Flow Simulations:
      Application to Arterial Bifurcations and Trees.
AB  - When blood flows through a bifurcation, red blood cells (RBCs) travel into side
      branches at different hematocrit levels, and it is even possible that all RBCs
      enter into one branch only, leading to a complete separation of plasma and RBCs.
      To quantify this phenomenon via particle-based mesoscopic simulations, we
      developed a general framework for open boundary conditions in multiphase flows
      that is effective even for high hematocrit levels. The inflow at the inlet is
      duplicated from a fully developed flow generated in a pilot simulation with
      periodic boundary conditions. The outflow is controlled by adaptive forces to
      maintain the flow rate and velocity gradient at fixed values, while the particles
      leaving the arteriole at the outlet are removed from the system. Upon validation
      of this approach, we performed systematic 3D simulations to study plasma skimming
      in arterioles of diameters 20 to 32 microns. For a flow rate ratio 6:1 at the
      branches, we observed the "all-or-nothing" phenomenon with plasma only entering
      the low flow rate branch. We then simulated blood-plasma separation in arteriolar
      bifurcations with different bifurcation angles and same diameter of the daughter
      branches. Our simulations predict a significant increase in RBC flux through the
      main daughter branch as the bifurcation angle is increased. Finally, we
      demonstrated the effectiveness of the new methodology in simulations of blood
      flow in vessels with multiple inlets and outlets, constructed using an
      angiogenesis model. 

PMID- 26317831
TI  - Levels and Age Dependency of Neurofilament Light and Glial Fibrillary Acidic
      Protein in Healthy Individuals and Their Relation to the Brain Parenchymal
      Fraction.
AB  - BACKGROUND: Neurofilament light (NFL) and Glial Fibrillary Acidic Protein (GFAP)
      are integral parts of the axonal and astrocytal cytoskeletons respectively and
      are released into the cerebrospinal fluid (CSF) in cases of cellular damage. In
      order to interpret the levels of these biomarkers in disease states, knowledge on
      normal levels in the healthy is required. Another biomarker for neurodegeneration
      is brain atrophy, commonly measured as brain parenchymal fraction (BPF) using
      magnetic resonance imaging (MRI). Potential correlations between levels of NFL,
      GFAP and BPF in healthy individuals have not been investigated. OBJECTIVES: To
      present levels of NFL and GFAP in healthy individuals stratified for age, and
      investigate the correlation between them as well as their correlation with BPF.
      METHODS: The CSF was analysed in 53 healthy volunteers aged 21 to 70 (1 sample
      missing for GFAP analysis) and 48 of the volunteers underwent determination of
      BPF using MRI. RESULTS: Mean (+/-SD) NFL was 355 ng/L (+/-214), mean GFAP was 421
      ng/L (+/-129) and mean BPF was 0.867 (+/-0.035). All three biomarkers correlated
      with age. NFL also correlated with both GFAP and BPF. When controlled for age,
      only the correlation between NFL and GFAP retained statistical significance.
      CONCLUSIONS: This study presents data on age-stratified levels of NFL and GFAP in
      the CSF of healthy individuals. There is a correlation between levels of NFL and
      GFAP and both increase with age. A correlation between NFL and BPF was also
      found, but did not retain statistical significance if controlled for age.

PMID- 26317832
TI  - Dietary Tributyrin Supplementation Attenuates Insulin Resistance and Abnormal
      Lipid Metabolism in Suckling Piglets with Intrauterine Growth Retardation.
AB  - Intrauterine growth retardation (IUGR) is associated with insulin resistance and
      lipid disorder. Tributyrin (TB), a pro-drug of butyrate, can attenuate
      dysfunctions in body metabolism. In this study, we investigated the effects of TB
      supplementation on insulin resistance and lipid metabolism in neonatal piglets
      with IUGR. Eight neonatal piglets with normal birth weight (NBW) and 16 neonatal
      piglets with IUGR were selected, weaned on the 7th day, and fed basic milk diets
      (NBW and IUGR groups) or basic milk diets supplemented with 0.1% tributyrin (IT
      group, IUGR piglets) until day 21 (n = 8). Relative parameters for lipid
      metabolism and mRNA expression were measured. Piglets with IUGR showed higher (P
      < 0.05) concentrations of insulin in the serum, higher (P < 0.05) HOMA-IR and
      total cholesterol, triglycerides (TG), non-esterified fatty acid (NEFA) in the
      liver, and lower (P < 0.05) enzyme activities (hepatic lipase [HL], lipoprotein
      lipase [LPL], total lipase [TL]) and concentration of glycogen in the liver than
      the NBW group. TB supplementation decreased (P < 0.05) the concentrations of
      insulin, HOMA-IR, low-density lipoprotein cholesterol, and high-density
      lipoprotein cholesterol in the serum, and the concentrations of TG and NEFA in
      the liver, and increased (P < 0.05) enzyme activities (HL, LPL, and TL) and
      concentration of glycogen in the liver of the IT group. The mRNA expression for
      insulin signal transduction pathway and hepatic lipogenic pathway (including
      transcription factors and nuclear factors) was significantly (P < 0.05) affected
      in the liver by IUGR, which was efficiently (P < 0.05) attenuated by diets
      supplemented with TB. TB supplementation has therapeutic potential for
      attenuating insulin resistance and abnormal lipid metabolism in IUGR piglets by
      increasing enzyme activities and upregulating mRNA expression, leading to an
      early improvement in the metabolic efficiency of IUGR piglets. 

PMID- 26317833
TI  - Modulation of Innate Immune Signalling by Lipid-Mediated MAVS Transmembrane
      Domain Oligomerization.
AB  - RIG-I-like receptors detect viral RNA in infected cells and promote
      oligomerization of the outer mitochondrial membrane protein MAVS to induce innate
      immunity to viral infection through type I interferon production. Mitochondrial
      reactive oxygen species (mROS) have been shown to enhance anti-viral MAVS
      signalling, but the mechanisms have remained obscure. Using a biochemical
      oligomerization-reporter fused to the transmembrane domain of MAVS, we found that
      mROS inducers promoted lipid-dependent MAVS transmembrane domain oligomerization
      in the plane of the outer mitochondrial membrane. These events were mirrored by
      Sendai virus infection, which similarly induced lipid peroxidation and promoted
      lipid-dependent MAVS transmembrane domain oligomerization. Our observations point
      to a role for mROS-induced changes in lipid bilayer properties in modulating
      antiviral innate signalling by favouring the oligomerization of MAVS
      transmembrane domain in the outer-mitochondrial membrane. 

PMID- 26317834
TI  - Association between physical activity and all cancer mortality: Dose-response
      meta-analysis of cohort studies.
AB  - The relationship between physical activity (PA) before cancer diagnosis and all
      cancer mortality among the general population is not well defined because of
      inconsistent results from published studies. Thus, the lack of a meta-analysis
      that addresses that issue prompted the current report. We conducted a literature
      search of PubMed and Web of Science to identify all relevant epidemiological
      studies published before February 28, 2015. We performed categorical and dose
      response meta-analyses to evaluate and quantify the association between pre
      diagnosis PA and all cancer mortality. A total of 32 prospective cohort studies
      involving 59,362 cancer deaths were included in this meta-analysis. The pooled
      relative risks (RRs) of all cancer mortality were 0.80 [95% confidence interval
      (CI) = 0.76-0.85)] for highest versus lowest PA group and 0.85 (95% CI = 0.82
      0.88) for PA versus non/occasional PA group. Dose-response analysis showed that
      the increment in pre-diagnosis PA level was associated with a decreased risk of
      cancer death continuously. Moreover, an increment of 10 MET-h/week was related to
      a 7% lower risk for all cancer mortality (RR = 0.93, 95% CI = 0.91-0.95). In
      conclusion, the present meta-analysis provides evidence of an inverse association
      between pre-diagnosis PA and all cancer mortality among the general population.
      High-quality epidemiological studies that employ standardized PA assessments and
      unified definitions of PA levels should be developed in future.

PMID- 26317836
TI  - A Pilot Study to Validate the Burn Center Pediatric Early Warning Score Tool in
      Clinical Practice.
AB  - The pediatric early warning score (PEWS) tool helps providers to detect subtle
      clinical deterioration in non-intensive care unit pediatric patients and
      intervene early to prevent significant adverse outcomes. Although widely used in
      general pediatrics, limited studies report on its validation; none report on use
      with burn-injured patients. New York-Presbyterian/Weill Cornell Medical Center
      modified a general PEWS system to a burn-specific PEWS and integrated its use
      into standard practice. This study investigated the external validity of the PEWS
      process in clinical practice. Fifty cases of patients aged 0 to 15.9 years
      admitted between January 2012 and June 2013, whose length of stay (LOS) more than
      3 days were selected for review from this cohort of n equal to 187. Demographics,
      total PEWS and score changes, and compliance with PEWS documentation and with
      resultant interventions were reviewed. Continuous variables are presented as mean
      +/- SD, P less than 0.05. Mean age, burn size, and LOS were 3.2 +/- 3.3 years,
      4.8 +/- 5.7%, and 9.8 +/- 7.0 days; 26% required grafting, and 50% were male. No
      mortalities occurred. One thousand six hundred and twelve PEWS from 1745
      opportunities were documented (92.4%). For all PEWS (n = 1612) and PEWS greater
      than 0 (n = 912), means were 0.9 +/- 1.2 and 1.6 +/- 1.2, respectively. Among the
      162 PEWS increase events, intake (54.1%) and output (4.5%) parameters increased
      most commonly. Of these, 129 PEWS increases (79.6%) were followed by an
      intervention that most commonly included text notation of score increase (93.7%),
      physician/physician assistant notification (70.5%), and feeding-tube insertion
      (25.6%). Patients with PEWS greater than 0 had similar age, LOS, and larger burn
      size (5.2% vs 1.4%, P < 0.05) than those with PEWS equal to 0. Compliance with
      PEWS performance and resultant actions based on score increases are high. Data
      support that even small changes in burn-injury specific PEWS stimulate provider
      discussion and intervention and support its validation; further studies on its
      effect on practice are warranted.

PMID- 26317835
TI  - Osteoprotective Effect of Echinocystic Acid, a Triterpone Component from Eclipta
      prostrata, in Ovariectomy-Induced Osteoporotic Rats.
AB  - Echinocystic acid (EA) is a natural triterpone enriched in various herbs and has
      been used for medicinal purposes in China. In the present study, we
      systematically examined the effects of EA on ovariectomy-induced osteoporosis in
      rats for the first time. Three-month-old female ovariectomy (OVX) Sprague-Dawley
      rats were used to evaluate the osteoprotective effect of EA. Results showed that
      administration of EA (5 or 15 mg/kg/day) for 12 weeks prevented lower levels of
      maximum stress and Young's modulus of femur induced by OVX. EA also recovered
      bone metabolic biomarkers levels in OVX rats, including osteocalcin, alkaline
      phosphatese, deoxypyridinoline, and urinary calcium and phosphorus. EA (5 and 15
      mg/kg/day) could prevent the alteration of total bone mineral density in the
      femur caused by OVX. However, only high dose (15 mg/kg/day) of EA significantly
      improved trabecular architecture, as evidenced by higher levels of bone
      volume/tissue volume, trabecula number, and trabecula thickness, and lower levels
      of trabecula separation and structure model index compared with OVX rats. In
      addition, EA treatment decresed the serum levels of IL-1beta and TNF-alpha in OVX
      rats. In conclusion, EA could prevent reduction of bone mass and strength and
      improve the cancellous bone structure and biochemical properties in OVX rats.
      Hence, EA may serve as a new candidate or a leading compound for anti
      osteoporosis. 

PMID- 26317838
TI  - [Rehabilitation Aftercare].

PMID- 26317837
TI  - Surgical Burn Care by Medecins Sans Frontieres-Operations Center Brussels: 2008
      to 2014.
AB  - Humanitarian organizations care for burns during crisis and while supporting
      healthcare facilities in low-income and middle-income countries. This study aimed
      to define the epidemiology of burn-related procedures to aid humanitarian
      response. In addition, operational data collected from humanitarian organizations
      are useful for describing surgical need otherwise unmet by national health
      systems. Procedures performed in operating theatres run by Medecins Sans
      Frontieres-Operations Centre Brussels (MSF-OCB) from July 2008 through June 2014
      were reviewed. Surgical specialist missions were excluded. Burn procedures were
      quantified, related to demographics and reason for humanitarian response, and
      described. A total of 96,239 operations were performed at 27 MSF-OCB projects in
      15 countries between 2008 and 2014. Of the 33,947 general surgical operations,
      4,280 (11%) were for burns. This proportion steadily increased from 3% in 2008 to
      24% in 2014. People receiving surgical care from conflict relief missions had
      nearly twice the odds of having a burn operation compared with people requiring
      surgery in communities affected by natural disaster (adjusted odds ratio, 1.94;
      95% confidence interval, 1.46-2.58). Nearly 70% of burn procedures were planned
      serial visits to the theatre. A diverse skill set was required. Unmet
      humanitarian assistance needs increased US$400 million dollars in 2013 in the
      face of an increasing number of individuals affected by crisis and a growing
      surgical burden. Given the high volume of burn procedures performed at MSF-OCB
      projects and the resource intensive nature of burn management, requisite planning
      and reliable funding are necessary to ensure quality for burn care in
      humanitarian settings.

PMID- 26317839
TI  - [Cost Effectiveness of Aftercare in the Cardiovascular Rehabilitation: A Five
      Years Follow-up Analysis].
AB  - OBJECTIVE: In Germany, the rehabilitative approaches towards patients with
      coronary artery events are not adequately sustainable despite the high costs.
      Both sustainability and cost effectiveness are the subjects of this 5-year
      analysis. METHODS: The study was initiated in 2004. One year recruiting phase was
      followed by 3 years aftercare with telephone as an intervention. This unicentric
      randomised controlled trial included 600 patients of rehabilitative aftercare
      (intervention group [IG] 271; control group [CG] 329). Data on (i) mortality,
      (ii) duration of retirement, (iii) type of retirement and (iv) status of
      retirement were obtained from the German Retirement Insurance.The analyses for
      cost-effectiveness are conducted for the intention-to-treat (ITT) approach. The
      general assessment basis of retirements (partial and full disability pensions)
      are average values for the year 2013 (year of the measurement). RESULTS: On the
      reporting date (31.12.2013), the values of the IG in part (early) retirement and
      full (early) retirement are higher than the CG (1.5 and 2.7%, n. s. and 7.4 and
      13.4%, respectively n. s.). The same applies for mortality (8.1 and 9.4%,
      respectively n. s.).The savings through lower pension payments amount to ? 1.55
      million for the adjusted ITT approach. From this, ? 130 080, which represents the
      cost of the aftercare (intervention), must be deducted. CONCLUSIONS: The results
      of the 5-year follow-up show that a part of pension payment could be reduced. The
      evidence of cost effectiveness, independently of the methodological approach, is
      strong. The saving potential is reached by half in both approaches.

PMID- 26317840
TI  - [Multidisciplinary Rehabilitation and Fast-track Rehabilitation after Knee
      Replacement: Faster, Better, Cheaper? A Survey and Systematic Review of
      Literature].
AB  - INTRODUCTION: The aim of multidisciplinary rehabilitation after total knee
      replacement (TKA) is to reduce postoperative complications and costs and enable
      faster convalescence. The goals of fast-track rehabilitation, as a
      multidisciplinary concept, are to reduce the length of hospital stay and achieve
      early functional improvements by optimizing the perioperative setting. METHOD: A
      literature review was carried out for the years 1960-2013. The search terms were:
      "rehabilitation", "training", "physiotherapy", "physical therapy", "recovery",
      "exercise program", "knee surgery", "TKA", "total knee replacement",
      "arthroplasty", "intensive", "multidisciplinary", "accelerated", "rapid" or "fast
      track". Only randomized controlled trials and metaanalyses were included. A
      survey was also performed to assess care as actually offered in orthopaedic
      rehabilitation clinics in North Rhine-Westphalia. RESULTS: A total of 729
      articles were identified of which 11 studies were included. Fast-track
      rehabilitation can significantly reduce both the duration of hospital stay and
      costs after TKA. Current studies showed that a better short-/middle-term clinical
      outcome might be achieved with multidisciplinary rehabilitation. However, a
      difference in the long-term outcome could not be observed. Our survey shows that
      most patients are admitted to a rehabilitation clinic in a state of poor general
      condition as well as decreased mobility and knee range of motion. CONCLUSIONS:
      Fast-track rehabilitation facilitates a shortened hospital stay as well as cost
      saving. It probably can be used to optimize the condition of the patient before
      admission to a rehabilitation facility.

PMID- 26317841
TI  - [Does the Success of Work-related Interventions in the Rehabilitation of
      Neurological Diseases Depend on the Return-to-Work Prognosis? A Re-analysis of 2
      Randomised Controlled Trials].
AB  - OBJECTIVE: The paper examines whether patients with neurological diseases and a
      poor return to work (RTW) prognosis gain more from work-related medical
      rehabilitation (WMR). METHODS: Re-analysis of matched samples of 2 randomised
      controlled trials (N=442; questionnaire at admission of rehabilitation and 15
      month follow-up). Linear regression models were used calculating the effect of
      the WMR dependent on the RTW prognosis. Primary outcome was time of sick leave in
      the follow-up and physical and mental health measured by the SF-36. As secondary
      outcomes, strategies of coping skills and work-related attitudes were defined.
      RESULTS: Only for patients with a high non-RTW risk could positive effects of WMR
      be demonstrated on mental health, coping skills and the scale "work as a
      resource". In the 15-month follow-up, there were no differences in effects on
      duration of sick leave and physical health. CONCLUSIONS: The results based on
      this analysis indicate that patients with neurological diseases derive benefit
      from WMR only if their empirical RTW prognosis is poor. However, this only
      applies for the mental health in the medium term. Our study confirms the previous
      findings that suggest different effectiveness of the WMR for patients with
      different RTW risk.

PMID- 26317842
TI  - [Interdisciplinary Cooperation as a Characteristic of Successful Rehabilitation
      Facilities--Results from the Project MeeR].
AB  - OBJECTIVE: To determine if there is a difference between successful and less
      successful rehabilitation facilities concerning their extent and quality of
      interdisciplinary cooperation? METHODS: This analysis is part of the project
      MeeR, that aims to identify characteristics of rehabilitation facilities related
      to successful rehabilitation. 6 facilities were recruited based on a quantitative
      analysis; 3 facilities that ranked as above average and 3 as below average in
      terms of their success in rehabilitating patients. Comprehensive qualitative data
      were collected on these 6 facilities. RESULTS: In above average rehabilitation
      facilities, the extent of interdisciplinary cooperation was higher than in below
      average facilities; the position of the medical profession was less dominant and
      there was a wider access to team meetings. DISCUSSION: Promotion of
      interdisciplinary cooperation is an important component for the improvement of
      the success of rehabilitation facilities.

PMID- 26317843
TI  - [Therapeutic Nursing in Neurological (Early-)Rehabilitation: A Grounded Theory
      Study].
AB  - PURPOSE: What is therapeutic nursing? This question is gaining relevance in the
      context of the billing of services in the DRG system (DRG=Diagnosis-Related
      Groups), because in paragraph 8-552 of the operations and procedures coding
      system (OPS), it is explicitly stated that therapeutic care must be carried out
      by specially trained personnel. To date, empirical results on therapeutic nursing
      in neurological early rehabilitation are sparse. The objective of the study is to
      develop a theory of therapeutic care in neurological early rehabilitation.
      MATERIALS AND METHODS: The study is based on the method of grounded theory. Open
      participatory observations (n=92) and episodic interviews (n=10) with nursing
      professionals and nursing auxiliaries were conducted in 5 inpatient
      rehabilitation clinics. RESULTS: The theory of therapeutic nursing includes 6
      categories: (1) nursing care, (2) observation/perception, (3) communication, (4)
      autonomy and individual needs of patients and their relatives, (5) multi
      professional team and (6) prerequisites. DISCUSSION: The results indicate which
      aspects are included in therapeutic nursing and the necessary prerequisites for
      delivering therapeutic nursing. Against this background, continuing education
      programs reveal conspicuous gaps in the area of knowledge transfer and
      application in practice. CONCLUSIONS: The results of the study should be taken
      into consideration and integrated in nursing education, both at the basic level
      and in continuing education.

PMID- 26317844
TI  - [Not Available].

PMID- 26317846
TI  - Does youth adiposity, or change in adiposity from youth to adulthood, predict
      metabolically healthy obesity in adulthood?
AB  - BACKGROUND: Individuals with metabolically healthy obesity (MHO) do not have the
      metabolic complications usually associated with obesity. OBJECTIVE: To examine
      whether youth adiposity, or change in adiposity from youth to adulthood, predicts
      MHO 20 years later. METHODS: A national sample of 2410 Australian participants
      had height, weight and waist circumference (WC) measured in 1985 (7-15 years old)
      and 2004-2006 (26-36 years old). A fasting blood sample was taken in 2004-2006.
      MHO was defined as body mass index (BMI) >=30 kg m(-2) , normal fasting glucose
      (<5.6 mmol L(-1) ), triglycerides (<1.695 mmol L(-1) ), high-density lipoprotein
      cholesterol (>1.036 mmol L(-1) men, > 1.295 mmol L(-1) women), blood pressure
      (<130/85 mmHg) and no medication for these conditions. Relative risks (RR) were
      calculated using log binomial regression and expressed per unit of youth BMI (or
      WC) z-score or change in BMI (or WC) z-score from youth to adulthood, adjusted
      for sex and youth age. RESULTS: In total 323 individuals were obese at follow-up,
      79 (24.5%) were MHO. Adult MHO was not associated with youth BMI (RR: 1.00,
      95%CI: 0.85-1.19) or WC (RR: 0.93, 95%CI: 0.79-1.11). Individuals were less
      likely to be MHO if they had larger increases in BMI (BMI RR: 0.74, 95%CI: 0.57
      0.97) or WC (RR: 0.70, 95%CI: 0.55-0.90) from youth to adulthood. CONCLUSIONS:
      Change in adiposity from youth to adulthood predicted adult MHO better than youth
      adiposity alone.

PMID- 26317845
TI  - Systematic review of the use of data from national childhood obesity surveillance
      programmes in primary care: a conceptual synthesis.
AB  - This study reviewed the use in primary care of national surveillance data for
      children to determine the data's potential utility to inform policy and practice
      decisions on how to prevent and treat childhood obesity. We reviewed the 28
      countries identified by the World Obesity Federation as having high-quality
      comparable body mass index data for children. Literature published from any
      period up to December 2013 was included. Peer review literature was searched
      using Web of Science (Core Collection, MEDLINE). Grey literature was searched
      using the Internet by country name, programme name and national health and
      government websites. We included studies that (i) use national surveillance
      obesity data in primary care, or (ii) explore practitioner or parent perspectives
      about the use of such data. The main uses of national surveillance data in
      primary care were to identify and recruit obese children and their parents to
      participate in school and general practice-based research and/or interventions,
      and to inform families of children's measurements. Findings indicate a need for
      school staff and practitioners to receive additional training and support to
      sensitively communicate with families. Translation of these findings into policy
      and practice could help to improve current uses of national child obesity
      surveillance data in primary care. 

PMID- 26317847
TI  - Characteristics of the Cross-Sectional Vorticity of the Natural Spawning Grounds
      of Schizothorax prenanti and a Vague-Set Similarity Model for Ecological
      Restoration.
AB  - Schizothorax prenanti is an endemic fish in the mountain rivers of southwestern
      China with unique protection value. To further explore the vortex motion of
      hydraulic habitats, which is closely related to the fish breeding process, the
      cross-sectional vorticity was used to evaluate the hydraulic conditions of the
      natural spawning habitat of S. prenanti. A coupled level-set and volume-of-fluid
      (CLSVOF) three-dimensional (3D) model was applied to simulate the hydraulic
      habitat of the Weimen reach, a typical natural spawning ground for S. prenanti in
      the upper Yangtze River. The model was used in conjunction with the Wilcoxon rank
      sum test to distinguish the distributions of vertical vorticity in spawning and
      non-spawning reaches. Statistical analysis revealed that the cross-sectional
      vorticity in spawning reaches was significantly greater than in non-spawning
      reaches, with likely biological significance in the spawning process. The range
      of cross-sectional mean values of vorticity was 0.17 s(-1)-0.35 s(-1) in areas
      with concentrated fish sperm and eggs; the minimum value was 0.17 s(-1), and the
      majority of values were greater than 0.26 s(-1). Based on this study, a vague-set
      similarity model was used to assess the effectiveness of ecological restoration
      by evaluating the similarity of the cross-sectional vorticity of the natural
      spawning reach and rehabilitated spawning reach after implementing ecological
      restoration measures. The outcome might provide a theoretical basis for the
      recovery of damaged S. prenanti spawning grounds and act as an important
      complement for the assessment of recovery effectiveness and as a useful reference
      for the coordination of ecological water use with the demands of hydraulic and
      hydropower engineering.

PMID- 26317848
TI  - The L3MBTL3 Methyl-Lysine Reader Domain Functions As a Dimer.
AB  - L3MBTL3 recognizes mono- and dimethylated lysine residues on histone tails. The
      recently reported X-ray cocrystal structures of the chemical probe UNC1215 and
      inhibitor UNC2533 bound to the methyl-lysine reading MBT domains of L3MBTL3
      demonstrate a unique and flexible 2:2 dimer mode of recognition. In this study,
      we describe our in vitro analysis of L3MBTL3 dimerization via its MBT domains and
      additionally show that this dimerization occurs within a cellular context in the
      absence of small molecule ligands. Furthermore, mutations to the first and second
      MBT domains abrogated L3MBTL3 dimerization both in vitro and in cells. These
      observations are consistent with the hypothesis that L3MBTL3 engages methylated
      histone tails as a dimer while carrying out its normal function and provides an
      explanation for the presence of repeated MBT domains within L3MBTL3. 

PMID- 26317849
TI  - Extensive Genomic Diversity among Bovine-Adapted Staphylococcus aureus: Evidence
      for a Genomic Rearrangement within CC97.
AB  - Staphylococcus aureus is an important pathogen associated with both human and
      veterinary disease and is a common cause of bovine mastitis. Genomic
      heterogeneity exists between S. aureus strains and has been implicated in the
      adaptation of specific strains to colonise particular mammalian hosts. Knowledge
      of the factors required for host specificity and virulence is important for
      understanding the pathogenesis and management of S. aureus mastitis. In this
      study, a panel of mastitis-associated S. aureus isolates (n = 126) was tested for
      resistance to antibiotics commonly used to treat mastitis. Over half of the
      isolates (52%) demonstrated resistance to penicillin and ampicillin but all were
      susceptible to the other antibiotics tested. S. aureus isolates were further
      examined for their clonal diversity by Multi-Locus Sequence Typing (MLST). In
      total, 18 different sequence types (STs) were identified and eBURST analysis
      demonstrated that the majority of isolates grouped into clonal complexes CC97,
      CC151 or sequence type (ST) 136. Analysis of the role of recombination events in
      determining S. aureus population structure determined that ST diversification
      through nucleotide substitutions were more likely to be due to recombination
      compared to point mutation, with regions of the genome possibly acting as
      recombination hotspots. DNA microarray analysis revealed a large number of
      differences amongst S. aureus STs in their variable genome content, including
      genes associated with capsule and biofilm formation and adhesion factors.
      Finally, evidence for a genomic arrangement was observed within isolates from
      CC97 with the ST71-like subgroup showing evidence of an IS431 insertion element
      having replaced approximately 30 kb of DNA including the ica operon and histidine
      biosynthesis genes, resulting in histidine auxotrophy. This genomic rearrangement
      may be responsible for the diversification of ST71 into an emerging bovine
      adapted subgroup. 

PMID- 26317850
TI  - Cochlear Delay and Medial Olivocochlear Functioning in Children with Suspected
      Auditory Processing Disorder.
AB  - Behavioral manifestations of processing deficits associated with auditory
      processing disorder (APD) have been well documented. However, little is known
      about their anatomical underpinnings, especially cochlear processing. Cochlear
      delays, a proxy for cochlear tuning, measured using stimulus frequency
      otoacoustic emission (SFOAE) group delay, and the influence of the medial
      olivocochlear (MOC) system activation at the auditory periphery was studied in 23
      children suspected with APD (sAPD) and 22 typically developing (TD) children.
      Results suggest that children suspected with APD have longer SFOAE group delays
      (possibly due to sharper cochlear tuning) and reduced MOC function compared to TD
      children. Other differences between the groups include correlation between MOC
      function and SFOAE delay in quiet in the TD group, and lack thereof in the sAPD
      group. MOC-mediated changes in SFOAE delay were in opposite directions between
      groups: increase in delay in TD vs. reduction in delay in the sAPD group. Longer
      SFOAE group delays in the sAPD group may lead to longer cochlear filter ringing,
      and potential increase in forward masking. These results indicate differences in
      cochlear and MOC function between sAPD and TD groups. Further studies are
      warranted to explore the possibility of cochlea as a potential site for
      processing deficits in APD. 

PMID- 26317851
TI  - A New Set of Chemical Starting Points with Plasmodium falciparum Transmission
      Blocking Potential for Antimalarial Drug Discovery.
AB  - The discovery of new antimalarials with transmission blocking activity remains a
      key issue in efforts to control malaria and eventually eradicate the disease.
      Recently, high-throughput screening (HTS) assays have been successfully applied
      to Plasmodium falciparum asexual stages to screen millions of compounds, with the
      identification of thousands of new active molecules, some of which are already in
      clinical phases. The same approach has now been applied to identify compounds
      that are active against P. falciparum gametocytes, the parasite stage responsible
      for transmission. This study reports screening results for the Tres Cantos
      Antimalarial Set (TCAMS), of approximately 13,533 molecules, against P.
      falciparum stage V gametocytes. Secondary confirmation and cytotoxicity assays
      led to the identification of 98 selective molecules with dual activity against
      gametocytes and asexual stages. Hit compounds were chemically clustered and
      analyzed for appropriate physicochemical properties. The TCAMS chemical space
      around the prioritized hits was also studied. A selection of hit compounds was
      assessed ex vivo in the standard membrane feeding assay and demonstrated complete
      block in transmission. As a result of this effort, new chemical structures not
      connected to previously described antimalarials have been identified. This new
      set of compounds may serve as starting points for future drug discovery programs
      as well as tool compounds for identifying new modes of action involved in malaria
      transmission. 

PMID- 26317852
TI  - Listeria monocytogenes Prevalence and Characteristics in Retail Raw Foods in
      China.
AB  - The prevalence and levels of Listeria monocytogenes in retail raw foods covering
      most provincial capitals in China were studied with testing of 1036 samples of
      vegetables, edible mushrooms, raw meat, aquatic products and quick-frozen
      products from September 2012 to January 2014. The total prevalence of Listeria
      monocytogenes was 20.0% (207/1036), and the most probable number (MPN) values of
      65.7% of the positive samples ranged from 0.3 to 110 MPN/g. Geographical
      differences were observed in this survey, and the results of both qualitative and
      quantitative methods indicated that the levels in the samples from North China
      were higher than those in the samples from South China. A total of 248 isolates
      were analyzed, of which approximately half belonged to molecular serogroup 1/2a
      3a (45.2%), followed by 1/2b-3b-7 (30.6%), 1/2c-3c (16.1%), 4b-4d-4e (5.2%) and
      4a-4c (2.8%). Most of the isolates carried hly (100%), inlB (98.8%), inlA
      (99.6%), inlC (98.0%) and inlJ (99.2%), and 44.8% of the isolates were llsX
      positive. Seventeen epidemic clones (ECs) were detected, with 7 strains belonging
      to ECI (2.8%) and 10 belonging to ECIII (4.03%). Resistance to clindamycin
      (46.8%) was commonly observed, and 59 strains (23.8%) were susceptible to all 14
      tested antibiotics, whereas 84 (33.9%) showed an intermediate level of resistance
      or were resistant to two or more antibiotics, including 7 multi-resistant strains
      that exhibited resistance to more than 10 antibiotics. The data obtained in the
      present study provides useful information for assessment of the possible risk
      posed to Chinese consumers, and this information will have a significant public
      health impact in China. Furthermore, the presence of virulence markers, epidemic
      clones, as well as the antibiotic resistance amongst the isolates strongly
      implies that many of these strains might be capable of causing listeriosis, and
      more accurate treatment of human listeriosis with effective antibiotics should be
      considered. This research represents a more full-scale and systematical
      investigation of the prevalence of L. monocytogenes in retail raw foods in China,
      and it provides baseline information for Chinese regulatory authorities that will
      aid in the formulation of a regulatory framework for controlling L. monocytogenes
      with the aim of improving the microbiological safety of raw foods. 

PMID- 26317853
TI  - Epigallocatechin Gallate/Layered Double Hydroxide Nanohybrids: Preparation,
      Characterization, and In Vitro Anti-Tumor Study.
AB  - In recent years, nanotechnology in merging with biotechnology has been employed
      in the area of cancer management to overcome the challenges of chemopreventive
      strategies in order to gain promising results. Since most biological processes
      occur in nano scale, nanoparticles can act as carriers of certain drugs or agents
      to deliver it to specific cells or targets. In this study, we intercalated
      Epigallocatechin-3-Gallate (EGCG), the most abundant polyphenol in green tea,
      into Ca/Al-NO3 Layered double hydroxide (LDH) nanoparticles, and evaluated its
      efficacy compared to EGCG alone on PC3 cell line. The EGCG loaded LDH nanohybrids
      were characterized by X-ray diffraction, Fourier transform infrared spectroscopy,
      transmission electron microscopy (TEM) and nanosizer analyses. The anticancer
      activity of the EGCG-loaded LDH was investigated in prostate cancer cell line
      (PC3) while the release behavior of EGCG from LDH was observed at pH 7.45 and
      4.25. Besides enhancing of apoptotic activity of EGCG, the results showed that
      intercalation of EGCG into LDH can improve the anti- tumor activity of EGCG over
      5-fold dose advantages in in-vitro system. Subsequently, the in-vitro release
      data showed that EGCG-loaded LDH had longer release duration compared to physical
      mixture, and the mechanism of diffusion through the particle was rate-limiting
      step. Acidic attack was responsible for faster release of EGCG molecules from LDH
      at pH of 4.25 compared to pH of 7.4. The results showed that Ca/Al-LDH
      nanoparticles could be considered as an effective inorganic host matrix for the
      delivery of EGCG to PC3 cells with controlled release properties. 

PMID- 26317855
TI  - rPbPga1 from Paracoccidioides brasiliensis Activates Mast Cells and Macrophages
      via NFkB.
AB  - BACKGROUND: The fungus Paracoccidioides brasiliensis is the leading etiological
      agent of paracoccidioidomycosis (PCM), a systemic granulomatous disease that
      typically affects the lungs. Cell wall components of P. brasiliensis interact
      with host cells and influence the pathogenesis of PCM. In yeast, many
      glycosylphosphatidylinositol (GPI)-anchored proteins are important in the initial
      contact with the host, mediating host-yeast interactions that culminate with the
      disease. PbPga1 is a GPI anchored protein located on the surface of the yeast P.
      brasiliensis that is recognized by sera from PCM patients. METHODOLOGY/PRINCIPAL
      FINDINGS: Endogenous PbPga1 was localized to the surface of P. brasiliensis yeast
      cells in the lungs of infected mice using a polyclonal anti-rPbPga1 antibody.
      Furthermore, macrophages stained with anti-CD38 were associated with P.
      brasiliensis containing granulomas. Additionally, rPbPga1 activated the
      transcription factor NFkB in the macrophage cell line Raw 264.7 Luc cells,
      containing the luciferase gene downstream of the NFkB promoter. After 24 h of
      incubation with rPbPga1, alveolar macrophages from BALB/c mice were stimulated to
      release TNF-alpha, IL-4 and NO. Mast cells, identified by toluidine blue
      staining, were also associated with P. brasiliensis containing granulomas. Co
      culture of P. Brasiliensis yeast cells with RBL-2H3 mast cells induced
      morphological changes on the surface of the mast cells. Furthermore, RBL-2H3 mast
      cells were degranulated by P. brasiliensis yeast cells, but not by rPbPga1, as
      determined by the release of beta-hexosaminidase. However, RBL-2H3 cells
      activated by rPbPga1 released the inflammatory interleukin IL-6 and also
      activated the transcription factor NFkB in GFP-reporter mast cells. The
      transcription factor NFAT was not activated when the mast cells were incubated
      with rPbPga1. CONCLUSIONS/SIGNIFICANCE: The results indicate that PbPga1 may act
      as a modulator protein in PCM pathogenesis and serve as a useful target for
      additional studies on the pathogenesis of P. brasiliensis.

PMID- 26317857
TI  - Experimental review of hypernuclear physics: recent achievements and future
      perspectives.
AB  - Since the shutdown of several old proton synchrotrons, which played a fundamental
      role in the second generation experiments in hypernuclear physics performed in
      Europe, USA and Japan, some new experimental setups aiming to achieve sub-MeV
      energy resolution have been operating for a long time. Over the last decade the
      hypernuclear physics community has been committed to carrying out several third
      generation experiments by exploiting the potential offered by new accelerators,
      such as a continuous electron beam machine and a phi-factory. Large data samples
      were collected on specific items thanks to dedicated facilities and experimental
      apparatuses. The attention was mainly focused on both high-resolution
      spectroscopy and the decay mode study of single Lambda-hypernuclei. Nowadays this
      phase is over but, until recently, important and, to some extent, unexpected
      results were achieved. An updated review of selected experimental results is
      presented, as well as a survey of perspectives for future studies. 

PMID- 26317856
TI  - Maternal Microbiome and Pregnancy Outcomes That Impact Infant Health: A Review.
AB  - The maternal microbiome is recognized as a key determinant of a range of
      important maternal and child health outcomes, and together with perinatal factors
      influences the infant microbiome. This article provides a summary review of
      research investigating (1) the role of the maternal microbiome in pregnancy
      outcomes known to adversely influence neonatal and infant health, including
      preterm birth, cardiometabolic complications of pregnancy such as preeclampsia
      and gestational diabetes, and excessive gestational weight gain; (2) factors with
      an established link to adverse pregnancy outcomes that are known to influence the
      composition of the maternal microbiome; and (3) strategies for promoting a
      healthy maternal microbiome, recognizing that much more research is needed in
      this area. 

PMID- 26317858
TI  - Neural Correlates of Empathy with Pain Show Habituation Effects. An fMRI Study.
AB  - BACKGROUND: Neuroimaging studies have demonstrated that the actual experience of
      pain and the perception of another person in pain share common neural substrates,
      including the bilateral anterior insular cortex and the anterior midcingulate
      cortex. As many fMRI studies include the exposure of participants to repeated,
      similar stimuli, we examined whether empathic neural responses were affected by
      habituation and whether the participants' prior pain experience influenced these
      habituation effects. METHOD: In 128 trials (four runs), 62 participants (31
      women, 23.0 +/- 4.2 years) were shown pictures of hands exposed to painful
      pressure (pain pictures) and unexposed (neutral pictures). After each trial, the
      participants rated the pain of the model. Prior to the experiment, participants
      were either exposed to the same pain stimulus (pain exposure group) or not (touch
      exposure group). In order to assess possible habituation effects, linear changes
      in the strength of the BOLD response to the pain pictures (relative to the
      neutral pictures) and in the ratings of the model's pain were evaluated across
      the four runs. RESULTS: Although the ratings of the model's pain remained
      constant over time, we found neural habituation in the bilateral
      anterior/midinsular cortex, the posterior midcingulate extending to dorsal
      posterior cingulate cortex, the supplementary motor area, the cerebellum, the
      right inferior parietal lobule, and the left superior frontal gyrus, stretching
      to the pregenual anterior cingulate cortex. The participant's prior pain
      experience did neither affect their ratings of the model's pain nor their
      maintenance of BOLD activity in areas associated with empathy. Interestingly,
      participants with high trait personal distress and fantasy tended to show less
      habituation in the anterior insula. CONCLUSION: Neural structures showed a
      decrease of the BOLD signal, indicating habituation over the course of 45
      minutes. This can be interpreted as a neuronal mechanism responding to the
      repeated exposure to pain depictions, which may be regarded as functional in a
      range of contexts.

PMID- 26317854
TI  - Role of Marine Natural Products in the Genesis of Antiviral Agents.

PMID- 26317859
TI  - Resolvins Decrease Oxidative Stress Mediated Macrophage and Epithelial Cell
      Interaction through Decreased Cytokine Secretion.
AB  - BACKGROUND: Inflammation is a key hallmark of ALI and is mediated through
      ungoverned cytokine signaling. One such cytokine, interleukin-1beta (IL-1beta)
      has been demonstrated to be the most bioactive cytokine in ALI patients.
      Macrophages are the key players responsible for IL-1beta secretion into the
      alveolar space. Following the binding of IL-1beta to its receptor, "activated"
      alveolar epithelial cells show enhanced barrier dysfunction, adhesion molecule
      expression, cytokine secretion, and leukocyte attachment. More importantly, it is
      an important communication molecule between the macrophage and alveolar
      epithelium. While the molecular determinants of this inflammatory event have been
      well documented, endogenous resolution processes that decrease IL-1beta secretion
      and resolve alveolar epithelial cell activation and tissue inflammation have not
      been well characterized. Lipid mediator Aspirin-Triggered Resolvin D1 (AT-RvD1)
      has demonstrated potent pro-resolutionary effects in vivo models of lung injury;
      however, the contribution of the alveoli to the protective benefits of this
      molecule has not been well documented. In this study, we demonstrate that AT-RvD1
      treatment lead to a significant decrease in oxidant induced macrophage IL-1beta
      secretion and production, IL-1beta-mediated cytokine secretion, adhesion molecule
      expression, leukocyte adhesion and inflammatory signaling. METHODS: THP-1
      macrophages were treated with hydrogen peroxide and extracellular ATP in the
      presence or absence of AT-RvD1 (1000-0.1 nM). A549 alveolar-like epithelial cells
      were treated with IL-1beta (10 ng/mL) in the presence or absence of AT-RvD1 (0.1
      MUM). Following treatment, cell lysate and cell culture supernatants were
      collected for Western blot, qPCR and ELISA analysis of pro-inflammatory
      molecules. Functional consequences of IL-1beta induced alveolar epithelial cell
      and macrophage activation were also measured following treatment with IL-1beta +/
      AT-RvD1. RESULTS: Results demonstrate that macrophages exposed to H2O2 and ATP
      in the presence of resolvins show decreased IL-1beta production and activity.
      A549 cells treated with IL-1beta in the presence of AT-RvD1 show a reduced level
      of proinflammatory cytokines IL-6 and IL-8. Further, IL-1beta-mediated adhesion
      molecule expression was also reduced with AT-RvD1 treatment, which was correlated
      with decreased leukocyte adhesion. AT-RvD1 treatment demonstrated reduced MAP
      Kinase signaling. Taken together, our results demonstrate AT-RvD1 treatment
      reduced IL-1beta-mediated alveolar epithelial cell activation. This is a key step
      in unraveling the protective effects of resolvins, especially AT-RvD1, during
      injury.

PMID- 26317860
TI  - Vision-Related Quality of Life and Appearance Concerns Are Associated with
      Anxiety and Depression after Eye Enucleation: A Cross-Sectional Study.
AB  - AIMS: To investigate the association of demographic, clinical and psychosocial
      variables with levels of anxiety and depression in participants wearing an ocular
      prosthesis after eye enucleation. METHODS: This cross-sectional study included
      195 participants with an enucleated eye who were attending an ophthalmic clinic
      for prosthetic rehabilitation between July and November 2014. Demographic and
      clinical data, and self-reported feelings of shame, sadness and anger were
      collected. Participants also completed the National Eye Institute Visual Function
      Questionnaire, the Facial Appearance subscale of the Negative Physical Self
      Scale, and the Hospital Anxiety and Depression Scale. Regression models were used
      to identify the factors associated with anxiety and depression. RESULTS: The
      proportion of participants with clinical anxiety was 11.8% and clinical
      depression 13.8%. More anxiety and depression were associated with poorer vision
      related quality of life and greater levels of appearance concerns. Younger age
      was related to greater levels of anxiety. Less educated participants and those
      feeling more angry about losing an eye are more prone to experience depression.
      Clinical variables were unrelated to anxiety or depression. CONCLUSIONS: Anxiety
      and depression are more prevalent in eye-enucleated patients than the general
      population, which brings up the issues of psychiatric support in these patients.
      Psychosocial rather than clinical characteristics were associated with anxiety
      and depression. Longitudinal studies need to be conducted to further elucidate
      the direction of causality before interventions to improve mood states are
      developed.

PMID- 26317861
TI  - Area-Level Socioeconomic Gradients in Overweight and Obesity in a Community
      Derived Cohort of Health Service Users - A Cross-Sectional Study.
AB  - BACKGROUND: Overweight and obesity lead to higher probability of individuals
      accessing primary care but adiposity estimates are rarely available at regional
      levels to inform health service planning. This paper analyses a large, community
      derived clinical database of objectively measured body mass index (BMI) to
      explore relationships with area-level socioeconomic disadvantage for informing
      regional level planning activities. MATERIALS AND METHODS: The study included
      91776 adults who had BMI objectively measured between 1 July 2009 and 30 June
      2011 by a single pathology provider. Demographic data and BMI were extracted and
      matched to 2006 national census socioeconomic data using geocoding. Adjusted odds
      ratios for overweight and obesity were calculated using sex-stratified logistic
      regression models with socioeconomic disadvantage of census collection district
      of residence as the independent variable. RESULTS: The prevalence of overweight
      or obesity was 79.2% (males) and 65.8% (females); increased with age to 74 years;
      and was higher in rural (74%) versus urban areas (71.4%) (p<0.001). Increasing
      socioeconomic disadvantage was associated with increasing prevalence of
      overweight (p<0.0001), obesity (p<0.0001) and overweight or obesity (p<0.0001) in
      women and obesity (p<0.0001) in men. Socioeconomic disadvantage was unrelated to
      overweight (p = 0.2024) and overweight or obesity (p = 0.4896) in males.
      CONCLUSION: It is feasible to link routinely-collected clinical data,
      representative of a discrete population, with geographic distribution of
      disadvantage, and to obtain meaningful area-level information useful for
      targeting interventions to improve population health. Our results demonstrate
      novel area-level socioeconomic gradients in overweight and obesity relevant to
      regional health service planning.

PMID- 26317862
TI  - Factors Associated with Primary School Teachers' Attitudes Towards the Inclusion
      of Students with Disabilities.
AB  - OBJECTIVE: Teachers' attitudes toward inclusion are often based on the practical
      implementation of inclusive education rather than a specific ideology and
      understanding of inclusiveness. This study aimed to identify the factors
      associated with primary school teachers' attitudes towards inclusion of students
      with all disabilities in regular schools. METHOD: Seventy four primary school
      teachers participated in a cross-sectional survey conducted in Western Australia.
      Teachers' attitudes and efficacy toward integration of students with disabilities
      were measured using the Opinions Relative to Integration of Students with
      Disabilities scale and Bandura's Teacher Efficacy scale respectively. RESULTS:
      Four teacher attributes-age, gender, teaching self-efficacy and training
      collectively explained 42% of the variability in teachers' attitude toward
      including students with disabilities. CONCLUSION: The current study further
      contributes to the accumulation of knowledge that can unpack the complex pattern
      of factors that should be considered to promote positive attitudes towards
      inclusive schools.

PMID- 26317863
TI  - Characterization of Precursor PfHsp60 in Plasmodium falciparum Cytosol during Its
      Asexual Development in Human Erythrocytes.
AB  - Mitochondrial heat shock protein 60 (Hsp60) is a nuclear encoded gene product
      that gets post-translationally translocated into the mitochondria. Using multiple
      approaches such as immunofluorescence experiments, isoelectric point analysis
      with two-dimensional gel electrophoresis, and mass spectrometric identification
      of the signal peptide, we show that Hsp60 from Plasmodium falciparum (PfHsp60)
      accumulates in the parasite cytoplasm during the ring, trophozoite, and schizont
      stages of parasite development before being imported into the parasite
      mitochondria. Using co-immunoprecipitation experiments with antibodies specific
      to cytoplasmic PfHsp90, PfHsp70-1, and PfHsp60, we show association of precursor
      PfHsp60 with cytoplasmic chaperone machinery. Metabolic labeling involving pulse
      and chase indicates translocation of the precursor pool into the parasite
      mitochondrion during chase. Analysis of results obtained with Geldanamycin
      treatment confirmed precursor PfHsp60 to be one of the clients for PfHsp90.
      Cytosolic chaperones bind precursor PfHsp60 prior to its import into the
      mitochondrion of the parasite. Our data suggests an inefficient co-ordination in
      the synthesis and translocation of mitochondrial PfHsp60 during asexual growth of
      malaria parasite in human erythrocytes. 

PMID- 26317864
TI  - Local IL-17 Production Exerts a Protective Role in Murine Experimental
      Glomerulonephritis.
AB  - IL-17 is a pro-inflammatory cytokine implicated in the pathogenesis of
      glomerulonephritis and IL-17 deficient mice are protected from nephrotoxic
      nephritis. However, a regulatory role for IL-17 has recently emerged. We describe
      a novel protective function for IL-17 in the kidney. Bone marrow chimeras were
      created using wild-type and IL-17 deficient mice and nephrotoxic nephritis was
      induced. IL-17 deficient hosts transplanted with wild-type bone marrow had worse
      disease by all indices compared to wild-type to wild-type bone marrow transplants
      (serum urea p<0.05; glomerular thrombosis p<0.05; tubular damage p<0.01),
      suggesting that in wild-type mice, IL-17 production by renal cells resistant to
      radiation is protective. IL-17 deficient mice transplanted with wild-type bone
      marrow also had a comparatively altered renal phenotype, with significant
      differences in renal cytokines (IL-10 p<0.01; IL-1beta p<0.001; IL-23 p<0.01),
      and macrophage phenotype (expression of mannose receptor p<0.05; inducible nitric
      oxide synthase p<0.001). Finally we show that renal mast cells are resistant to
      radiation and produce IL-17, suggesting they are potential local mediators of
      disease protection. This is a novel role for intrinsic cells in the kidney that
      are radio-resistant and produce IL-17 to mediate protection in nephrotoxic
      nephritis. This has clinical significance as IL-17 blockade is being trialled as
      a therapeutic strategy in some autoimmune diseases. 

PMID- 26317865
TI  - Income and Physical Activity among Adults: Evidence from Self-Reported and
      Pedometer-Based Physical Activity Measurements.
AB  - This study examined the relationship between income and physical activity by
      using three measures to illustrate daily physical activity: the self-reported
      physical activity index for leisure-time physical activity, pedometer-based total
      steps for overall daily physical activity, and pedometer-based aerobic steps that
      reflect continuous steps for more than 10 min at a time. The study population
      consisted of 753 adults from Finland (mean age 41.7 years; 64% women) who
      participated in 2011 in the follow-up of the ongoing Young Finns study. Ordinary
      least squares models were used to evaluate the associations between income and
      physical activity. The consistency of the results was explored by using register
      based income information from Statistics Finland, employing the instrumental
      variable approach, and dividing the pedometer-based physical activity according
      to weekdays and weekend days. The results indicated that higher income was
      associated with higher self-reported physical activity for both genders. The
      results were robust to the inclusion of the control variables and the use of
      register-based income information. However, the pedometer-based results were
      gender-specific and depended on the measurement day (weekday vs. weekend day). In
      more detail, the association was positive for women and negative or non-existing
      for men. According to the measurement day, among women, income was positively
      associated with aerobic steps despite the measurement day and with totals steps
      measured on the weekend. Among men, income was negatively associated with aerobic
      steps measured on weekdays. The results indicate that there is an association
      between income and physical activity, but the association is gender-specific and
      depends on the measurement type of physical activity. 

PMID- 26317866
TI  - Longitudinal Metabolomics Profiling of Parkinson's Disease-Related alpha
      Synuclein A53T Transgenic Mice.
AB  - Metabolic homeostasis is critical for all biological processes in the brain. The
      metabolites are considered the best indicators of cell states and their rapid
      fluxes are extremely sensitive to cellular changes. While there are a few studies
      on the metabolomics of Parkinson's disease, it lacks longitudinal studies of the
      brain metabolic pathways affected by aging and the disease. Using ultra-high
      performance liquid chromatography and tandem mass spectroscopy (UPLC/MS), we
      generated the metabolomics profiling data from the brains of young and aged male
      PD-related alpha-synuclein A53T transgenic mice as well as the age- and gender
      matched non-transgenic (nTg) controls. Principal component and unsupervised
      hierarchical clustering analyses identified distinctive metabolites influenced by
      aging and the A53T mutation. The following metabolite set enrichment
      classification revealed the alanine metabolism, redox and acetyl-CoA biosynthesis
      pathways were substantially disturbed in the aged mouse brains regardless of the
      genotypes, suggesting that aging plays a more prominent role in the alterations
      of brain metabolism. Further examination showed that the interaction effect of
      aging and genotype only disturbed the guanosine levels. The young A53T mice
      exhibited lower levels of guanosine compared to the age-matched nTg controls. The
      guanosine levels remained constant between the young and aged nTg mice, whereas
      the aged A53T mice showed substantially increased guanosine levels compared to
      the young mutant ones. In light of the neuroprotective function of guanosine, our
      findings suggest that the increase of guanosine metabolism in aged A53T mice
      likely represents a protective mechanism against neurodegeneration, while
      monitoring guanosine levels could be applicable to the early diagnosis of the
      disease. 

PMID- 26317867
TI  - Hypertonic Saline Dextran Ameliorates Organ Damage in Beagle Hemorrhagic Shock.
AB  - OBJECTIVE: The goal of this study was to investigate the effect of hypertonic
      saline with 6% Dextran-70 (HSD) resuscitation on organ damage and the
      resuscitation efficiency of the combination of HSD and lactated ringers (LR) in a
      model of hemorrhage shock in dogs. METHODS: Beagles were bled to hold their mean
      arterial pressure (MAP) at 50 +/- 5 mmHg for 1 h. After hemorrhage, beagles were
      divided into three groups (n = 7) to receive pre-hospital resuscitation for 1 h
      (R1): HSD (4 ml/kg), LR (40 ml/kg), and HSD+LR (a combination of 4 ml/kg HSD and
      40 ml/kg LR). Next, LR was transfused into all groups as in-hospital
      resuscitation (R2). After two hours of observation (R3), autologous blood was
      transfused. Hemodynamic responses and systemic oxygenation were measured at
      predetermined phases. Three days after resuscitation, the animals were sacrificed
      and tissues including kidney, lung, liver and intestinal were obtained for
      pathological analysis. RESULTS: Although the initial resuscitation with HSD was
      shown to be faster than LR with regard to an ascending MAP, the HSD group showed
      a similar hemodynamic performance compared to the LR group throughout the
      experiment. Compared with the LR group, the systemic oxygenation performance in
      the HSD group was similar but showed a lower venous-to-arterial CO2 gradient (Pv
      aCO2) at R3 (p < 0.05). Additionally, the histology score of the kidneys, lungs
      and liver were significantly lower in the HSD group than in the LR group (p <
      0.05). The HSD+LR group showed a superior hemodynamic response but higher
      extravascular lung water (EVLW) and lower arterial oxygen tension (PaO2) than the
      other groups (p < 0.05). The HSD+LR group showed a marginally improved systemic
      oxygenation performance and lower histology score than other groups. CONCLUSIONS:
      Resuscitation after hemorrhagic shock with a bolus of HSD showed a similar
      hemodynamic response compared with LR at ten times the volume of HSD, but HSD
      showed superior efficacy in organ protection. Our findings suggest that
      resuscitation with the combination of HSD and LR in the pre-hospital setting is
      an effective treatment.

PMID- 26317869
TI  - Success and Failure of Parliamentary Motions: A Social Dilemma Approach.
AB  - Parliamentary motions are a vital and frequently used element of political
      control in democratic regimes. Despite their high incidence and potential impact
      on the political fate of a government and its policies, we know relatively little
      about the conditions under which parliamentary motions are likely to be accepted
      or rejected. Current collective decision-making models use a voting power
      framework in which power and influence of the involved parties are the main
      predictors. We propose an alternative, social dilemma approach, according to
      which a motion's likelihood to be accepted depends on the severity of the social
      dilemma underlying the decision issue. Actor- and dilemma-centered hypotheses are
      developed and tested with data from a stratified random sample of 822 motions
      that have been voted upon in the Dutch Parliament between September 2009 and
      February 2011. The social dilemma structure of each motion is extracted through
      content coding, applying a cognitive mapping technique developed by Anthony,
      Heckathorn and Maser. Logistic regression analyses are in line with both, actor
      centered and social-dilemma centered approaches, though the latter show stronger
      effect sizes. Motions have a lower chance to be accepted if voting potential is
      low, the proposer is not from the voting party, and if the problem underlying the
      motion reflects a prisoner's dilemma or a pure competition game as compared to a
      coordination game. The number of proposing parties or a battle of the sexes
      structure does not significantly affect the outcome. 

PMID- 26317868
TI  - Effect of Trimethyltin Chloride on Slow Vacuolar (SV) Channels in Vacuoles from
      Red Beet (Beta vulgaris L.) Taproots.
AB  - In the present study, patch-clamp techniques have been used to investigate the
      effect of trimethyltin chloride (Met3SnCl) on the slow vacuolar (SV) channels in
      vacuoles from red beet (Beta vulgaris L.) taproots. Activity of SV channels has
      been measured in whole-vacuole and cytosolic side-out patch configurations. It
      was found that addition of trimethyltin chloride to the bath solution suppressed,
      in a concentration-dependent manner, SV currents in red beet vacuoles. The time
      constant, tau, increased significantly in the presence of the organotin. When
      single channel activity was analyzed, only little channel activity could be
      recorded at 100 MUM Met3SnCl. Trimethyltin chloride added to the bath medium
      significantly decreased (by ca. threefold at 100 MUM Met3SnCl and at 100 mV
      voltage, as compared to the control medium) the open probability of single
      channels. Single channel recordings obtained in the presence and absence of
      trimethyltin chloride showed that the organotin only slightly (by <10%) decreased
      the unitary conductance of single channels. It was also found that Met3SnCl
      significantly diminished the number of SV channel openings, whereas it did not
      change the opening times of the channels. Taking into account the above and the
      fact that under the here applied experimental conditions (pH = 7.5) Met3SnCl is a
      non-dissociated (more lipophilic) compound, we suggest that the suppression of SV
      currents observed in the presence of the organotin results probably from its
      hydrophobic properties allowing this compound to translocate near the selectivity
      filter of the channel. 

PMID- 26317870
TI  - Reference Gene Selection for qPCR Analysis in Tomato-Bipartite Begomovirus
      Interaction and Validation in Additional Tomato-Virus Pathosystems.
AB  - Quantitative Polymerase Chain Reaction (qPCR) is currently the most sensitive
      technique used for absolute and relative quantification of a target gene
      transcript, requiring the use of appropriated reference genes for data
      normalization. To accurately estimate the relative expression of target tomato
      (Solanum lycopersicum L.) genes responsive to several virus species in reverse
      transcription qPCR analysis, the identification of reliable reference genes is
      mandatory. In the present study, ten reference genes were analyzed across a set
      of eight samples: two tomato contrasting genotypes ('Santa Clara', susceptible,
      and its near-isogenic line 'LAM 157', resistant); subjected to two treatments
      (inoculation with Tomato chlorotic mottle virus (ToCMoV) and its mock-inoculated
      control) and in two distinct times after inoculation (early and late). Reference
      genes stability was estimated by three statistical programs (geNorm, NormFinder
      and BestKeeper). To validate the results over broader experimental conditions, a
      set of ten samples, corresponding to additional three tomato-virus pathosystems
      that included tospovirus, crinivirus and tymovirus + tobamovirus, was analyzed
      together with the tomato-ToCMoV pathosystem dataset, using the same algorithms.
      Taking into account the combined analyses of the ranking order outputs from the
      three algorithms, TIP41 and EF1 were identified as the most stable genes for
      tomato-ToCMoV pathosystem, and TIP41 and EXP for the four pathosystems together,
      and selected to be used as reference in the forthcoming expression qPCR analysis
      of target genes in experimental conditions involving the aforementioned tomato
      virus pathosystems. 

PMID- 26317871
TI  - Functional Basis of Microorganism Classification.
AB  - Correctly identifying nearest "neighbors" of a given microorganism is important
      in industrial and clinical applications where close relationships imply similar
      treatment. Microbial classification based on similarity of physiological and
      genetic organism traits (polyphasic similarity) is experimentally difficult and,
      arguably, subjective. Evolutionary relatedness, inferred from phylogenetic
      markers, facilitates classification but does not guarantee functional identity
      between members of the same taxon or lack of similarity between different taxa.
      Using over thirteen hundred sequenced bacterial genomes, we built a novel
      function-based microorganism classification scheme, functional-repertoire
      similarity-based organism network (FuSiON; flattened to fusion). Our scheme is
      phenetic, based on a network of quantitatively defined organism relationships
      across the known prokaryotic space. It correlates significantly with the current
      taxonomy, but the observed discrepancies reveal both (1) the inconsistency of
      functional diversity levels among different taxa and (2) an (unsurprising) bias
      towards prioritizing, for classification purposes, relatively minor traits of
      particular interest to humans. Our dynamic network-based organism classification
      is independent of the arbitrary pairwise organism similarity cut-offs
      traditionally applied to establish taxonomic identity. Instead, it reveals
      natural, functionally defined organism groupings and is thus robust in handling
      organism diversity. Additionally, fusion can use organism meta-data to highlight
      the specific environmental factors that drive microbial diversification. Our
      approach provides a complementary view to cladistic assignments and holds
      important clues for further exploration of microbial lifestyles. Fusion is a more
      practical fit for biomedical, industrial, and ecological applications, as many of
      these rely on understanding the functional capabilities of the microbes in their
      environment and are less concerned with phylogenetic descent. 

PMID- 26317873
TI  - Diversity-Oriented Approach to Cyclophanes via Fischer Indolization and Ring
      Closing Metathesis: Substrate-Controlled Stereochemical Outcome in RCM.
AB  - Here, we report a new and diversity-oriented approach to macrocyclic cyclophanes
      by a Grignard reaction, followed by Fischer indolization and ring-closing
      metathesis (RCM) as key steps. The configuration of the double bond formed during
      the RCM depends upon the order of synthetic sequence used. Fischer indolization
      followed by RCM delivers the cis isomer, whereas RCM followed by Fischer
      indolization gives the trans isomer. 

PMID- 26317872
TI  - Overuse and Underuse of Antiosteoporotic Treatments According to Highly
      Influential Osteoporosis Guidelines: A Population-Based Cross-Sectional Study in
      Spain.
AB  - Inappropriate prescribing of antiosteoporotic medications has been observed;
      however, the joint study of both overuse and underuse has barely been attempted.
      Spain, with its high utilization rates, constitutes a good example to assess
      differences in over and under use according to diverse highly-influential
      osteoporosis guidelines (HIOG) worldwide. We used data of a population-based
      cross-sectional study including 824 post-menopausal women >=50 years old living
      in the city of Valencia, Spain and aimed to estimate the percentage of women
      eligible for treatment, and the proportion of overuse and underuse of
      antiosteoporotic treatment according to HIOG. The prevalence of antiosteoporotic
      treatment in postmenopausal women >= 50 in Valencia was 20.9% (95%CI:17.6-24.4).
      The type of antiosteoporotic drugs prescribed varied greatly depending on the
      medical specialty responsible of the initial prescription. When applying the
      HIOG, the percentage of women 50 and over who should be treated varied from less
      than 9% to over 44%. In real terms, from the approximately eight million women of
      50 years old and over in Spain, the number eligible for treatment would range
      from 0.7 to 3.8 million, depending on the guideline used. A huge proportion of
      inappropriate treatments was found when applying these guidelines to the Spanish
      population, combining a high overuse (42-78% depending on the guideline used) and
      underuse (7-41%). In conclusion, we found that the pharmacological management of
      osteoporosis in women of 50 and over in this population combines an important
      overuse and, to a lesser extent, underuse, although the level of
      inappropriateness varied strikingly depending on the CPG used. It seems urgent to
      reduce treatment overuse without neglecting underuse, as is urgent an attempt to
      reach wider agreement worldwide regarding osteoporosis management, in order to
      facilitate appropriate treatment and development of policies to reduce
      effectively treatment inappropriateness. 

PMID- 26317875
TI  - "Monogamy" in Primates: Variability, Trends, and Synthesis: Introduction to
      special issue on Primate Monogamy.
AB  - This paper is the introduction to a special issue on "'Monogamy' in Primates:
      Variability, Trends, and Synthesis." The term "monogamy" has undergone
      redefinition over the years, and is now generally understood to refer to certain
      social characteristics rather than to genetic monogamy. However, even the term
      "social monogamy" is used loosely to refer to species which exhibit a spectrum of
      social structures, mating patterns, and breeding systems. Papers in this volume
      address key issues including whether or not our definitions of monogamy should
      change in order to better represent the social and mating behaviors that
      characterize wild primates; whether or not primate groups traditionally
      considered monogamous are actually so (by any definition); ways in which captive
      studies can contribute to our understanding of monogamy; and what selective
      pressures might have driven the evolution of monogamous and non-monogamous single
      female breeding systems.

PMID- 26317876
TI  - Correction: The Gametocytes of Leucocytozoon sabrazesi Infect Chicken
      Thrombocytes, Not Other Blood Cells.

PMID- 26317877
TI  - Fetuin-A levels and free leptin index are reduced in patients with chronic
      lymphocytic leukemia: a hospital-based case-control study.
AB  - There are limited data on fetuin-A, soluble leptin receptor (sOB-R) and free
      leptin index (FLI) in patients with chronic lymphocytic leukemia (CLL). The aim
      of this study was to compare circulating fetuin-A, sOB-R levels and FLI between
      95 patients with CLL and 95 matched controls, as well as among different stages
      of CLL. Circulating fetuin-A was significantly lower in cases than controls
      (241.9 +/- 99.2 vs. 288.8 +/- 127.7 MUg/mL; p = 0.005). Although circulating sOB
      R levels were similar between groups, FLI was lower in cases than controls (0.45
      +/- 0.42 vs. 0.67 +/- 0.57; p = 0.003). Furthermore, lower fetuin-A or FLI, but
      not sOB-R, were independently associated with CLL (p < 0.05), particularly among
      overweight/obese individuals. Fetuin-A, s-OB-R and FLI were similar between
      different stages of CLL severity, or between symptomatic and asymptomatic
      disease. In conclusion, circulating fetuin-A and FLI, but not sOB-R, were lower
      in patients with CLL than controls, a finding warranting further investigation. 

PMID- 26317878
TI  - Challenges in Delivering Smaller Doses of Insulin.

PMID- 26317879
TI  - Maternal Glycemia and Fetal Well-Being: Continuous Glucose Monitoring and
      Continuous Cardiotocography.

PMID- 26317881
TI  - Saccharothrixones A-D, Tetracenomycin-Type Polyketides from the Marine-Derived
      Actinomycete Saccharothrix sp. 10-10.
AB  - Saccharothrixones A-C (1-3), three new aromatic polyketide seco-tetracenomycins,
      and saccharothrixone D (4), a new tetracenomycin analogue possessing opposite
      configurations at all of the stereogenic centers, were isolated from the marine
      derived actinomycete Saccharothrix sp. 10-10. Compounds 1-3 represent the first
      examples of seco-tetracenomycins where the quinone ring B is cleaved and re
      formed into a furanone ring. Their structures were elucidated by spectroscopic
      analyses and ECD calculations. The absolute configuration of 4 was confirmed by
      single-crystal X-ray diffraction analysis. Saccharothrixone D (4) showed in vitro
      cytotoxic activity against the HepG2 cancer cell line with an IC50 value of 7.5
      MUM. 

PMID- 26317880
TI  - Comparison of Metabolic Outcomes in Children Diagnosed with Type 1 Diabetes
      Through Research Screening (Diabetes Autoimmunity Study in the Young [DAISY])
      Versus in the Community.
AB  - BACKGROUND: Children with positive islet autoantibodies monitored prospectively
      avoid metabolic decompensation at type 1 diabetes (T1D) diagnosis. However, the
      effects of early diagnosis and treatment on preservation of insulin secretion and
      long-term metabolic control are unknown. We compared characteristics of children
      detected through research screening (Diabetes Autoimmunity Study in the Young
      [DAISY]) versus community controls at baseline and, in a subset, 6- and 12-month
      metabolic outcomes. MATERIALS AND METHODS: This was a case-control study
      comparing DAISY children with T1D to children diagnosed in the general community.
      All participants underwent mixed-meal tolerance testing; a subset wore a
      continuous glucose monitoring (CGM) device. Fasting and stimulated C-peptide
      levels, insulin dose-adjusted hemoglobin A1c (IDAA1c), and CGM variables were
      compared. RESULTS: Children (21 DAISY, 21 community) were enrolled and matched by
      age, time of diagnosis, and diabetes duration; 18 were enrolled within 2 months
      and 24 within 2.5 years on average from diagnosis. In the overall group and the
      subgroup of participants enrolled 2.5 years from diagnosis, there were no IDAA1c
      or C-peptide differences between DAISY versus community children. The subgroup of
      DAISY versus community children enrolled near diagnosis, however, had lower
      baseline hemoglobin A1c (6.5+/-1.4% vs. 9.2+/-2.9%; P=0.0007) and IDAA1c (7.4+/
      2.1% vs. 11.2+/-3.5%; P=0.04) and higher stimulated C-peptide (2.5+/-0.5 vs.
      1.6+/-0.2 ng/mL; P=0.02). In this subgroup, IDAA1c differences persisted at 6
      months but not at 1 year. CGM analyses revealed lower minimum overnight glycemia
      in community children (72 vs. 119 mg/dL; P=0.01). CONCLUSIONS: Favorable patterns
      of IDAA1c and C-peptide seen in research-screened versus community-diagnosed
      children with T1D within 2 months of diagnosis are no longer apparent 1 year from
      diagnosis.

PMID- 26317882
TI  - Standardization of high content imaging and informatics.

PMID- 26317884
TI  - High-content assays for characterizing the viability and morphology of 3D cancer
      spheroid cultures.
AB  - There is an increasing interest in using three-dimensional (3D) spheroids for
      modeling cancer and tissue biology to accelerate translation research.
      Development of higher throughput assays to quantify phenotypic changes in
      spheroids is an active area of investigation. The goal of this study was to
      develop higher throughput high-content imaging and analysis methods to
      characterize phenotypic changes in human cancer spheroids in response to compound
      treatment. We optimized spheroid cell culture protocols using low adhesion U
      bottom 96- and 384-well plates for three common cancer cell lines and improved
      the workflow with a one-step staining procedure that reduces assay time and
      minimizes variability. We streamlined imaging acquisition by using a maximum
      projection algorithm that combines cellular information from multiple slices
      through a 3D object into a single image, enabling efficient comparison of
      different spheroid phenotypes. A custom image analysis method was implemented to
      provide multiparametric characterization of single-cell and spheroid phenotypes.
      We report a number of readouts, including quantification of marker-specific cell
      numbers, measurement of cell viability and apoptosis, and characterization of
      spheroid size and shape. Assay performance was assessed using established
      anticancer cytostatic and cytotoxic drugs. We demonstrated concentration-response
      effects for different readouts and measured IC50 values, comparing 3D spheroid
      results to two-dimensional cell cultures. Finally, a library of 119 approved
      anticancer drugs was screened across a wide range of concentrations using HCT116
      colon cancer spheroids. The proposed methods can increase performance and
      throughput of high-content assays for compound screening and evaluation of
      anticancer drugs with 3D cell models. 

PMID- 26317883
TI  - HCS campaign to identify selective inhibitors of IL-6-induced STAT3 pathway
      activation in head and neck cancer cell lines.
AB  - Signal transducer and activator of transcription factor 3 (STAT3) is
      hyperactivated in head and neck squamous cell carcinomas (HNSCC). Cumulative
      evidence indicates that IL-6 production by HNSCC cells and/or stromal cells in
      the tumor microenvironment activates STAT3 and contributes to tumor progression
      and drug resistance. A library of 94,491 compounds from the Molecular Library
      Screening Center Network (MLSCN) was screened for the ability to inhibit
      interleukin-6 (IL-6)-induced pSTAT3 activation. For contractual reasons, the
      primary high-content screening (HCS) campaign was conducted over several months
      in 3 distinct phases; 1,068 (1.1%) primary HCS actives remained after cytotoxic
      or fluorescent outliers were eliminated. One thousand one hundred eighty-seven
      compounds were cherry-picked for confirmation; actives identified in the primary
      HCS and compounds selected by a structural similarity search of the remaining
      MLSCN library using hits identified in phases I and II of the screen. Actives
      were confirmed in pSTAT3 IC50 assays, and an IFNgamma-induced pSTAT1 activation
      assay was used to prioritize selective inhibitors of STAT3 activation that would
      not inhibit STAT1 tumor suppressor functions. Two hundred three concentration
      dependent inhibitors of IL-6-induced pSTAT3 activation were identified and 89 of
      these also produced IC50s against IFN-gamma-induced pSTAT1 activation. Forty-nine
      compounds met our hit criteria: they reproducibly inhibited IL-6-induced pSTAT3
      activation by >=70% at 20 MUM; their pSTAT3 activation IC50s were <=25 MUM; they
      were >=2-fold selective for pSTAT3 inhibition over pSTAT1 inhibition; a cross
      target query of PubChem indicated that they were not biologically promiscuous;
      and they were >=90% pure. Twenty-six chemically tractable hits that passed
      filters for nuisance compounds and had acceptable drug-like and ADME-Tox
      properties by computational evaluation were purchased for characterization. The
      hit structures were distributed among 5 clusters and 8 singletons. Twenty-four
      compounds inhibited IL-6-induced pSTAT3 activation with IC50s <=20 MUM and 13
      were >=3-fold selective versus inhibition of pSTAT1 activation. Eighteen hits
      inhibited the growth of HNSCC cell lines with average IC50s <= 20 MUM. Four
      chemical series were progressed into lead optimization: the
      guanidinoquinazolines, the triazolothiadiazines, the amino alcohols, and an
      oxazole-piperazine singleton. 

PMID- 26317887
TI  - Thermodynamics of Ion Pair Formations Between Charged Poly(Amino Acid)s.
AB  - Electrostatic interactions between the positively and negatively charged amino
      acids in proteins play an important role in macromolecular stability, binding,
      and recognition. Numerous amino acids in proteins are ionizable and may exist in
      negatively (e.g., Glu, Asp, Cys, Tyr) or positively (e.g., Arg, Lys, His, Orn)
      charged form dependent on pH and their pKas. In this work, isothermal titration
      calorimetry was used to determine the average standard values of thermodynamic
      parameters (the Gibbs free energy, enthalpy, entropy, and the heat capacity) of
      interaction between the positively charged amino acid homopolymers (polyarginine,
      polylysine, and polyornithine) and the negatively charged homopolymers
      (polyaspartic and polyglutamic acids). These values are of potential use in the
      computational models of interacting proteins and other biological macromolecules.
      The study showed that oppositely charged poly(amino acid)s bound each other with
      the stoichiometry of one positive to one negative charge. Arginine bound to the
      negatively charged amino acids with exothermic enthalpy and higher affinity than
      lysine. This result also suggests that positive charges in proteins should not be
      considered entirely equivalent if carried by lysine or arginine. The difference
      in binding energy of arginine and lysine association with the negatively charged
      amino acids was attributed to the enthalpy of the second ionic hydrogen bond
      formation between the guanidine and carboxylic groups. Despite the favorable
      enthalpic contribution, all such ion pair formation reactions were largely
      entropy-driven. Consistent with previously observed ionic interactions, the
      positive heat capacity was always observed during the amino acid ion pair
      formation. 

PMID- 26317888
TI  - The association between working hours and sleep disturbances according to
      occupation and gender.
AB  - We attempted to explore the relationship between working hours and sleep
      disturbance according to occupation and gender among Korean workers. Data were
      derived from the third Korean Working Conditions Survey, conducted in 2011 by the
      Korea Occupational Safety and Health Agency. From a total of 50,032 workers,
      34,783 salaried contract workers were selected. Work hours were categorized as
      <40, 40-48 (reference), 49-60, and >60 h/week. The outcome variable was sleep
      disturbance, which was assessed by a single question item (During the past 12
      months, have you experienced sleep disturbance or insomnia?). Multiple survey
      logistic regression models were performed after adjusting with age, education
      level, marital status, self-rated health, salary, shift work, smoking and alcohol
      drinking. Gender and occupation were stratified in these models. The adjusted
      odds ratio (OR) for sleep disturbance in male non-manual workers with long work
      hours (>60 h/week) was 3.017 [95% confidence interval (CI) 1.956-4.653]. In
      female non-manual workers who work 49-60 working hour per week, the OR was 1.525
      (95% CI 1.034-2.249). Long working hours can be a risk factor for sleep
      disturbance in Korean workers. The association was especially prominent in male
      non-manual workers.

PMID- 26317889
TI  - New Advance in Computational Chemistry:  Full Quantum Mechanical ab Initio
      Computation of Streptavidin-Biotin Interaction Energy.
AB  - Benchmark full quantum mechanical Hartree-Fock calculation has been carried out
      to compute interaction energies for the streptavidin-biotin binding complex. In
      this report, the entire streptavidin-biotin interaction system with a total of
      1775 atoms is treated by quantum mechanics. The full quantum energy calculation
      for this protein system is made possible by applying a recently developed MFCC
      approach in which the protein molecule is decomposed into amino-acid-based
      fragments that are properly capped. Ab initio calculations are performed at the
      Hartree-Fock level with a 3-21G basis set. The energies are computed for
      geometries of the binding complex near two configurations, corresponding to the
      crystal structure of the binding complex and a minimum energy geometry found from
      molecular force field, respectively. Comparisons are made of the computed ab
      initio energies with those from a force field. The present calculation shows that
      ab initio binding energies (at HF/3-21G level) are almost 30 kcal/mol larger than
      those given by a force field. 

PMID- 26317890
TI  - The Right to Grief.

PMID- 26317891
TI  - Aspartate facilitates mitochondrial function, growth arrest and survival during
      doxorubicin exposure.
AB  - Genomic screens of doxorubicin toxicity in S. cerevisiae have identified numerous
      mutants in amino acid and carbon metabolism which express increased doxorubicin
      sensitivity. This work examines the effect of amino acid metabolism on
      doxorubicin toxicity. S. cerevisiae were treated with doxorubicin in combination
      with a variety of amino acid supplements. Strains of S. cerevisiae with mutations
      in pathways utilizing aspartate and other metabolites were examined for
      sensitivity to doxorubicin. S. cerevisiae cultures exposed to doxorubicin in
      minimal media showed significantly more toxicity than cultures exposed in rich
      media. Supplementing minimal media with aspartate, glutamate or alanine reduced
      doxorubicin toxicity. Cell cycle response was assessed by examining the budding
      pattern of treated cells. Cultures exposed to doxorubicin in minimal media
      arrested growth with no apparent cell cycle progression. Aspartate
      supplementation allowed cultures exposed to doxorubicin in minimal media to
      arrest after one division with a budding pattern and survival comparable to
      cultures exposed in rich media. Aspartate provides less protection from
      doxorubicin in cells mutant in either mitochondrial citrate synthase (CIT1) or
      NADH oxidase (NDI1), suggesting aspartate reduces doxorubicin toxicity by
      facilitating mitochondrial function. These data suggest glycolysis becomes less
      active and mitochondrial respiration more active following doxorubicin exposure. 

PMID- 26317893
TI  - In Situ EQCM Study Examining Irreversible Changes the Sulfur-Carbon Cathode in
      Lithium-Sulfur Batteries.
AB  - In situ EQCM experiments were used to investigate the stability and roughness
      changes occurring in a sulfur-carbon cathode utilized for a Li-S battery during
      the charge-discharge process. Results show that the sulfur-carbon cathode gains
      mass during the first discharge plateau (~2.4 V) due to the formation of the long
      chain polysulfides during the discharge (lithiation) process. However, further
      discharge to below 2.4 V yields an increase in the crystal resistance (Rc)
      suggesting the sulfur-carbon cathode becomes rougher. During the charge
      (delithiation) process, the roughness of the sulfur-carbon cathode decreases.
      Time dependent measurements show that the electrode surface becomes rougher with
      the deeper discharge, with the change occurring following a step to 1.5 V. The
      sulfur-carbon cathode exhibits stable Rc and frequency behavior initially, but
      then becomes rougher in subsequent following cycles. 

PMID- 26317894
TI  - Journal Narratives Are Now Free Access.

PMID- 26317892
TI  - Plant mitochondrial dynamics and the role of membrane lipids.
AB  - Mitochondria are highly dynamic organelles that are continuously shaped by the
      antagonistic fission and fusion processes. The major machineries of mitochondrial
      fission and fusion, as well as mechanisms that regulate the function of key
      players in these processes have been analyzed in different experimental systems.
      In plants however, the mitochondrial fusion machinery is still largely unknown,
      and the regulatory mechanisms of the fission machinery are just beginning to be
      elucidated. This review focuses on the molecular mechanisms underlying plant
      mitochondrial dynamics and regulation of some of the key factors, especially the
      roles of membrane lipids such as cardiolipin. 

PMID- 26317895
TI  - Best single-slice location to measure visceral adipose tissue on paediatric CT
      scans and the relationship between anthropometric measurements, gender and VAT
      volume in children.
AB  - OBJECTIVE: Visceral adipose tissue (VAT) is a significant risk factor for obesity
      related metabolic diseases. This study investigates (1) the best single CT slice
      location for predicting total abdominal VAT volume in paediatrics and (2) the
      relationship between waist circumference (WC), sagittal diameter (SD), gender and
      VAT volume. METHODS: A random sample of 130 paediatric abdomen CT scans,
      stratified according to age and gender, was collected. Three readers measured VAT
      area at each intervertebral level between T12 and S1 using ImageJ analysis
      (National Institute of Health, Bethesda, MD) software by thresholding -190 to -30
      HU and manually segmenting VAT. Single-slice VAT measurements were correlated
      with total VAT volume to identify the most representative slice. WC and SD were
      measured at L3-L4 and L4-L5 slices, respectively. Regression analysis was used to
      evaluate WC, SD and gender as VAT volume predictors. RESULTS: Interviewer and
      intraviewer reliability were excellent (intraclass correlation coefficient =
      0.99). Although VAT measured at multiple slices correlated strongly with
      abdominal VAT, only one slice in females at L2-L3 and two slices in males at L1
      L2 and L5-S1 were strongly correlated across all age groups. Linear regression
      analysis showed that WC was strongly correlated with VAT volume (beta = 0.970, p
      < 0.001). CONCLUSION: Single-slice VAT measurements are highly reproducible.
      Measurements performed at L2-L3 in females and L1-L2 or L5-S1 in males were most
      representative of VAT. WC is indicative of VAT. ADVANCES IN KNOWLEDGE: VAT should
      be measured at L2-L3 in female children and at either L1-L2 or L5-S1 in males. WC
      is a strong indicator of VAT in children.

PMID- 26317896
TI  - Interventional MSK procedures: the hip.
AB  - Percutaneous musculoskeletal procedures are widely accepted as low invasive,
      highly effective, efficient and safe methods in a vast amount of hip pathologies
      either in diagnostic or in therapeutic management. Hip intra-articular injections
      are used for the symptomatic treatment of osteoarthritis. Peritendinous or
      intrabursal corticosteroid injections can be used for the symptomatic treatment
      of greater trochanteric pain syndrome and anterior iliopsoas impingement. In past
      decades, the role of interventional radiology has rapidly increased in metastatic
      disease, thanks to the development of many ablative techniques. Image-guided
      percutaneous ablation of skeletal metastases provides a minimally invasive
      treatment option that appears to be a safe and effective palliative treatment for
      localized painful lytic lesion. Methods of tumour destruction based on
      temperature, such as radiofrequency ablation (RFA) and cryotherapy, are performed
      for the management of musculoskeletal metastases. MR-guided focused ultrasound
      surgery provides a non-invasive alternative to these ablative methods.
      Cementoplasty is now widely used for pain management and consolidation of
      acetabular metastases and can be combined with RFA. RFA is also used to treat
      benign tumours, namely osteoid osteomas. New interventional procedures such as
      percutaneous screw fixation are also proposed to treat non-displaced or minimally
      displaced acetabular roof fractures. 

PMID- 26317897
TI  - Hyperbaric oxygen therapy palliates lipopolysaccharide-induced acute lung injury
      in rats by upregulating AQP1 and AQP5 expression.
AB  - PURPOSE: Hyperbaric oxygen (HBO) therapy has been suggested to palliate acute
      lung injury (ALI), but the mechanisms involved are not well understood. This
      study is to elucidate the involvement of AQP1 and AQP5 in the HBO related ALI
      therapy. MATERIALS AND METHODS: lipopolysaccharide (LPS) was administrated into
      SD rats to obtain ALI models. Pressure of oxygen (PaO2) and carbon dioxide
      (PaCO2) in arterial blood and oxygenation index in rats after LPS and HBO
      treatments were determined. Pathological changes of the lungs were examined by
      hematoxylin and eosin staining. Alteration of TNF-alpha level during LPS and HBO
      treatments was evaluated with ELISA analysis. Western blot was employed to assess
      the expression of AQP1 and AQP5. RESULTS: Blood gas indexes were largely
      decreased by LPS administration, which responded to HBO. Pathological examination
      showed that the inflammation symptoms in lungs induced by LPS were also palliated
      after HBO preconditioning. LPS induced the expression of TNF-alpha at a high
      level which could be downregulated by HBO and TNF-alpha antagonist treatments.
      Results of AQP1 and AQP5 determination found that HBO and TNF-alpha antagonist
      would upregulate the expression of AQP1 and AQP5 which was inhibited in rats with
      ALI. CONCLUSIONS: HBO therapy palliated LPS-induced ALI in rats by downregulating
      TNF-alpha expression. HBO also upregulated AQP1 and AQP5 expression. These
      results could serve as guidelines for the full understanding of ALI therapy by
      HBO, thus achieving maximized therapeutic efficiency.

PMID- 26317898
TI  - MicroRNA-940 promotes tumor cell invasion and metastasis by downregulating ZNF24
      in gastric cancer.
AB  - Growing evidence indicates that microRNA (miRNA) plays a vital role in
      progression and metastasis of gastric cancer (GC). However, the underlying
      mechanism of miRNA-mediated metastasis has not been fully understood. Recently,
      miRNA-940 (miR-940) was found to be overexpressed in GC, which correlated with
      malignant progression and poor survival. Mechanistically, we found that miR-940
      promoted GC cell migration, invasion, and metastasis in vivo by directly and
      functionally repressing the expression of Zinc Finger Transcription Factor 24
      (ZNF24). Importantly, upregulation of ZNF24 could re-inhibit miR-940-induced
      migration and invasion. Hence, we demonstrated the oncogenic role of miR-940 in
      GC, finding that miR-940 promoted GC progression by directly downregulating ZNF24
      expression, and targeting miR-940 could serve as a novel strategy for future GC
      therapy. 

PMID- 26317899
TI  - Genomic amplification of 9p24.1 targeting JAK2, PD-L1, and PD-L2 is enriched in
      high-risk triple negative breast cancer.
AB  - We used DNA content flow cytometry followed by oligonucleotide array based
      comparative genomic hybridization to survey the genomes of 326 tumors, including
      41 untreated surgically resected triple negative breast cancers (TNBC). A high
      level (log2ratio >= 1) 9p24 amplicon was found in TNBC (12/41), glioblastomas
      (2/44), and colon carcinomas (2/68). The shortest region of overlap for the
      amplicon targets 9p24.1 and includes the loci for PD-L1, PD-L2, and JAK2 (PDJ
      amplicon). In contrast this amplicon was absent in ER+ (0/8) and HER2+ (0/15)
      breast tumors, and in pancreatic ductal adenocarcinomas (0/150). The PDJ amplicon
      in TNBCs was correlated with clinical outcomes in group comparisons by two-sample
      t-tests for continuous variables and chi-squared tests for categorical variables.
      TNBC patients with the PDJ amplicon had a worse outcome with worse disease-free
      and overall survival. Quantitative RT-PCR confirmed that the PDJ amplicon in TNBC
      is associated with elevated expression of JAK2 and of the PD-1 ligands. These
      initial findings demonstrate that the PDJ amplicon is enriched in TNBC, targets
      signaling pathways that activate the PD-1 mediated immune checkpoint, and
      identifies patients with a poor prognosis.

PMID- 26317900
TI  - Combinatorial high-throughput experimental and bioinformatic approach identifies
      molecular pathways linked with the sensitivity to anticancer target drugs.
AB  - Effective choice of anticancer drugs is important problem of modern medicine. We
      developed a method termed OncoFinder for the analysis of new type of biomarkers
      reflecting activation of intracellular signaling and metabolic molecular
      pathways. These biomarkers may be linked with the sensitivity to anticancer
      drugs. In this study, we compared the experimental data obtained in our
      laboratory and in the Genomics of Drug Sensitivity in Cancer (GDS) project for
      testing response to anticancer drugs and transcriptomes of various human cell
      lines. The microarray-based profiling of transcriptomes was performed for the
      cell lines before the addition of drugs to the medium, and experimental growth
      inhibition curves were built for each drug, featuring characteristic IC50 values.
      We assayed here four target drugs - Pazopanib, Sorafenib, Sunitinib and
      Temsirolimus, and 238 different cell lines, of which 11 were profiled in our
      laboratory and 227 - in GDS project. Using the OncoFinder-processed
      transcriptomic data on ~600 molecular pathways, we identified pathways showing
      significant correlation between pathway activation strength (PAS) and IC50 values
      for these drugs. Correlations reflect relationships between response to drug and
      pathway activation features. We intersected the results and found molecular
      pathways significantly correlated in both our assay and GDS project. For most of
      these pathways, we generated molecular models of their interaction with known
      molecular target(s) of the respective drugs. For the first time, our study
      uncovered mechanisms underlying cancer cell response to drugs at the high
      throughput molecular interactomic level. 

PMID- 26317901
TI  - PIWIL1 destabilizes microtubule by suppressing phosphorylation at Ser16 and RLIM
      mediated degradation of Stathmin1.
AB  - Human PIWIL1, alias HIWI, is a member of Piwi protein family and expressed in
      various tumors. However, the underlying mechanism of PIWIL1 in tumorigenesis
      remains largely unknown. Stathmin1 is a cytosolic phosphoprotein which has a
      critical role in regulating microtubule dynamics and is overexpressed in many
      cancers. Here we report that PIWIL1 can directly bind to Stathmin1. Meanwhile,
      PIWIL1 can up-regulate the expression of Stathmin1 through inhibiting ubiquitin
      mediated degradation induced by an E3 ubiquitin ligase RLIM. Furthermore, PIWIL1
      can also reduce phosphorylation level of Stathmin1 at Ser-16 through inhibiting
      the interaction between CaMKII and Stathmin1. Our results showed that PIWIL1
      suppresses microtubule polymerization, and promotes cell proliferation and
      migration via Stathmin1 for the first time. Our study reveals a novel mechanism
      for PIWIL1 in tumorigenesis. 

PMID- 26317902
TI  - Characterization of tumor infiltrating lymphocytes in paired primary and
      metastatic renal cell carcinoma specimens.
AB  - Renal cell carcinoma (RCC) is one of the most chemo- and radio-resistant
      malignancies, with poor associated patient survival if the disease metastasizes.
      With recent advances in immunotherapy, particularly with PD-1/PD-L1 blockade,
      outcomes are improving, but a substantial subset of patients does not respond to
      the new agents. Identifying such patients and improving the therapeutic ratio has
      been a challenge, although much effort has been made to study PD-1/PD-L1 status
      in pre-treatment tumor. However, tumor infiltrating lymphocyte (TIL) content
      might also be predictive of response, and our goal was to characterize TIL
      content and PD-L1 expression in RCC tumors from various anatomic sites. Utilizing
      a quantitative immunofluorescence technique, TIL subsets were examined in matched
      primary and metastatic specimens. In metastatic specimens, we found an
      association between low CD8+ to Foxp3+ T-cell ratios and high levels of PD-L1.
      High PD-L1-expressing metastases were also found to be associated with tumors
      that were high in both CD4+ and Foxp3+ T-cell content. Taken together these
      results provide the basis for combining agents that target the PD-1/PD-L1 pathway
      with agonist of immune activation, particularly in treating RCC metastases with
      unfavorable tumor characteristics and microenvironment. In addition, CD8+ TIL
      density and CD8:Foxp3 T-cell ratio were higher in primary than metastatic
      specimens, supporting the need to assess distant sites for predictive biomarkers
      when treating disseminated disease.

PMID- 26317903
TI  - Bortezomib inhibits Burkitt's lymphoma cell proliferation by downregulating
      sumoylated hnRNP K and c-Myc expression.
AB  - Bortezomib (Velcal) was the first proteasome inhibitor to be approved by the US
      Food and Drug Administration to treat patients with relapsed/refractory multiple
      myelomas. Previous studies have demonstrated that bortezomib inhibits tumor cell
      proliferation and induces apoptosis by blocking the nuclear factor (NF)-kappaB
      pathway. However, the exact mechanism by which bortezomib induces cancer cell
      apoptosis is still not well understood. In this study, we found that bortezomib
      significantly inhibited cell proliferation in both human Burkitt's lymphoma CA46
      and Daudi cells. Through proteomic analysis, we found that bortezomib treatment
      changed the expression of various proteins in distinct functional categories
      including unfolding protein response (UPS), RNA processing, protein targeting and
      biosynthesis, apoptosis, and signal transduction. Among the proteins with altered
      expression, hnRNP K, hnRNP H, Hsp90alpha, Grp78, and Hsp7C were common to both
      Daudi and CA46 cells. Interestingly, bortezomib treatment downregulated the
      expression of high-molecular-weight (HMw) hnRNP K and c-Myc but upregulated the
      expression of low-molecular-weight (LMw) hnRNP K. Moreover, cell proliferation
      was significantly correlated with high expression of HMw hnRNP K and c-Myc. HMw
      and LMw hnRNP K were identified as sumoylated and desumoylated hnRNP K,
      respectively. Using transient transfection, we found that sumoylated hnRNP K
      increased c-Myc expression at the translational level and contributed to cell
      proliferation, and that Lys422 of hnRNP K is the candidate sumoylated residue.
      Our results suggest that besides inhibiting the ubiquitin-proteasome pathway,
      bortezomib may inhibit cell proliferation by downregulating sumoylated hnRNP K
      and c-Myc expression in Burkitt's lymphoma cells. 

PMID- 26317905
TI  - Retained Dermal Filler in the Upper Eyelid Masquerading as Periorbital Edema.

PMID- 26317906
TI  - A Novel Treatment of Herpes Zoster Pain With Pulsed Laser Irradiation.

PMID- 26317904
TI  - MiR-215, an activator of the CTNNBIP1/beta-catenin pathway, is a marker of poor
      prognosis in human glioma.
AB  - MicroRNA-215 (miR-215) promotes tumor growth in various human malignancies.
      However, its role has not yet been determined in human glioma. Here, we found
      that levels of miR-215 were higher in glioma tissues than in corresponding non
      neoplastic brain tissue. High miR-215 expression was correlated with higher World
      Health Organization (WHO) grades and shorter overall survival. Multivariate and
      univariate analysis indicated that miR-215 expression was an independent
      prognostic factor. We also found that TGF-beta1, phosphorylated beta-catenin,
      alpha-SMA, and fibronectin were increased in glioma tissues. Additionally,
      CTNNBIP1, a direct target of miR-215, was decreased in glioma compared to
      adjacent normal tissue. These data indicate that miR-215 activates Wnt/beta
      catenin signaling by increasing beta-catenin phosphorylation, alpha-SMA
      expression, and fibronectin expression. It promotes TGF-beta1-induced oncogenesis
      by suppressing CTNNBIP1 in glioma. In summary, miR-215 is overexpressed in human
      glioma, is involved in TGF-beta1-induced oncogenesis, and can be used as a marker
      of poor prognosis in glioma patients. 

PMID- 26317907
TI  - A Practical Tie-Over Technique: Surgical Scrub Sponge.

PMID- 26317908
TI  - Closure of Chronic Ulcer Localized on the Scalp Previously Irradiated Using a
      Fenestration Technique.

PMID- 26317909
TI  - Mutational Analysis of Rab3 Function for Controlling Active Zone Protein
      Composition at the Drosophila Neuromuscular Junction.
AB  - At synapses, the release of neurotransmitter is regulated by molecular machinery
      that aggregates at specialized presynaptic release sites termed active zones. The
      complement of active zone proteins at each site is a determinant of release
      efficacy and can be remodeled to alter synapse function. The small GTPase Rab3
      was previously identified as playing a novel role that controls the distribution
      of active zone proteins to individual release sites at the Drosophila
      neuromuscular junction. Rab3 has been extensively studied for its role in the
      synaptic vesicle cycle; however, the mechanism by which Rab3 controls active zone
      development remains unknown. To explore this mechanism, we conducted a mutational
      analysis to determine the molecular and structural requirements of Rab3 function
      at Drosophila synapses. We find that GTP-binding is required for Rab3 to traffick
      to synapses and distribute active zone components across release sites.
      Conversely, the hydrolytic activity of Rab3 is unnecessary for this function.
      Through a structure-function analysis we identify specific residues within the
      effector-binding switch regions that are required for Rab3 function and determine
      that membrane attachment is essential. Our findings suggest that Rab3 controls
      the distribution of active zone components via a vesicle docking mechanism that
      is consistent with standard Rab protein function.

PMID- 26317912
TI  - Importance of Geometric Phase Effects in Ultracold Chemistry.
AB  - It is demonstrated that the inclusion of the geometric phase has an important
      effect on ultracold chemical reaction rates. The effect appears in rotationally
      and vibrationally resolved integral cross sections as well as cross sections
      summed over all product quantum states. The effect arises from interference
      between scattering amplitudes of two reaction pathways: a direct path and a
      looping path that encircle the conical intersection between the two lowest
      adiabatic electronic potential energy surfaces. It is magnified when the two
      scattering amplitudes have comparable magnitude and they scatter into the same
      angular region which occurs in the isotropic scattering characteristic of the
      ultracold regime (s-wave scattering). Results are presented for the O + OH -> H +
      O2 reaction for total angular momentum quantum number J = 0-5. Large geometric
      phase effects occur for collision energies below 0.1 K, but the effect vanishes
      at higher energies when contributions from different partial waves are included.
      It is also qualitatively demonstrated that the geometric phase effect can be
      modulated by applying an external electric field allowing the possibility of
      quantum control of chemical reactions in the ultracold regime. In this case, the
      geometric phase plays the role of a "quantum switch" which can turn the reaction
      "on" or "off". 

PMID- 26317911
TI  - Direct Exposure to Ethanol Disrupts Junctional Cell-Cell Contact and Hippo-YAP
      Signaling in HL-1 Murine Atrial Cardiomyocytes.
AB  - Direct exposure of cardiomyocytes to ethanol causes cardiac damage such as
      cardiac arrythmias and apoptotic cell death. Cardiomyocytes are connected to each
      other through intercalated disks (ID), which are composed of a gap junction (GJ),
      adherens junction, and desmosome. Changes in the content as well as the
      subcellular localization of connexin43 (Cx43), the main component of the cardiac
      GJ, are reportedly involved in cardiac arrythmias and subsequent damage.
      Recently, the hippo-YAP signaling pathway, which links cellular physical status
      to cell proliferation, differentiation, and apoptosis, has been implicated in
      cardiac homeostasis under physiological as well as pathological conditions. This
      study was conducted to explore the possible involvement of junctional
      intercellular communication, mechanotransduction through cytoskeletal
      organization, and the hippo-YAP pathway in cardiac damage caused by direct
      exposure to ethanol. HL-1 murine atrial cardiac cells were used since these cells
      retain cardiac phenotypes through ID formation and subsequent synchronous
      contraction. Cells were exposed to 0.5-2% ethanol; significant apoptotic cell
      death was observed after exposure to 2% ethanol for 48 hours. A decrease in Cx43
      levels was already observed after 3 hours exposure to 2% ethanol, suggesting a
      rapid degradation of this protein. Upon exposure to ethanol, Cx43 translocated
      into lysosomes. Cellular cytoskeletal organization was also dysregulated by
      ethanol, as demonstrated by the disruption of myofibrils and intermediate
      filaments. Coinciding with the loss of cell-cell adherence, decreased
      phosphorylation of YAP, a hippo pathway effector, was also observed in ethanol
      treated cells. Taken together, the results provide evidence that cells exposed
      directly to ethanol show 1) impaired cell-cell adherence/communication, 2)
      decreased cellular mechanotransduction by the cytoskeleton, and 3) a suppressed
      hippo-YAP pathway. Suppression of hippo-YAP pathway signaling should be effective
      in maintaining cellular homeostasis in cardiomyocytes exposed to ethanol. 

PMID- 26317913
TI  - Genomic Comparison of Translocating and Non-Translocating Escherichia coli.
AB  - Translocation of E. coli across the gut epithelium can result in fatal sepsis in
      post-surgical patients. In vitro and in vivo experiments have identified the
      existence of a novel pathotype of translocating E. coli (TEC) that employs an
      unknown mechanism for translocating across epithelial cells to the mesenteric
      lymph nodes and the blood stream in both humans and animal models. In this study
      the genomes of four TEC strains isolated from the mesenteric lymph nodes of a
      fatal case of hospitalised patient (HMLN-1), blood of pigs after experimental
      shock (PC-1) and after non-lethal haemorrhage in rats (KIC-1 and KIC-2) were
      sequenced in order to identify the genes associated with their adhesion and/or
      translocation. To facilitate the comparison, the genomes of a non-adhering, non
      translocating E. coli (46-4) and adhering but non-translocating E. coli (73-89)
      were also sequenced and compared. Whole genome comparison revealed that three
      (HMLN-1, PC-1 and KIC-2) of the four TEC strains carried a genomic island that
      encodes a Type 6 Secretion System that may contribute to adhesion of the bacteria
      to gut epithelial cells. The human TEC strain HMLN-1 also carried the invasion
      ibeA gene, which was absent in the animal TEC strains and is likely to be
      associated with host-specific translocation. Phylogenetic analysis revealed that
      the four TEC strains were distributed amongst three distinct E. coli phylogroups,
      which was supported by the presence of phylogroup specific fimbriae gene
      clusters. The genomic comparison has identified potential genes that can be
      targeted with knock-out experiments to further characterise the mechanisms of E.
      coli translocation. 

PMID- 26317914
TI  - Identifying Targeted Strategies to Improve Smoking Cessation Support for Cancer
      Patients.
AB  - INTRODUCTION: Although smoking causes adverse outcomes in cancer patients, most
      oncology providers do not regularly provide smoking cessation support. The
      purpose of this study was to identify key areas that can be targeted to improve
      delivery of evidence-based cessation support for cancer patients. METHODS: In
      2012, the International Association for the Study of Lung Cancer surveyed members
      asking about tobacco assessment and cessation practices for cancer patients.
      Responses from 1153 physician level oncology providers were analyzed to evaluate
      the effects of respondent demographics, tobacco use perceptions, and perceived
      barriers to providing cessation support on practice patterns. RESULTS:
      Respondents from the United States generally reported higher rates of asking
      about tobacco use, advising patients to quit, and assisting patients in quitting
      smoking. Work setting, time since completing a terminal degree, percent of time
      devoted to clinical care, and history of tobacco use were generally associated
      with asking about tobacco use and advising patients to quit, but not associated
      with discussing medications or actively treating patients. The dominant
      multivariate barriers to providing cessation support were a lack of clinician
      education or experience and lack of available resources to refer patients for
      smoking cessation support. Patient resistance to treatment, inability for
      patients to quit smoking, or feeling that smoking was not an important part of
      cancer outcome or cancer care had less meaningful associations with providing
      support. CONCLUSIONS: Improving clinician education and developing dedicated
      resources to provide cessation support were identified as ideal targets to
      address for improving cessation support for cancer patients.

PMID- 26317915
TI  - Impact of Positive Nodal Metastases in Patients with Thymic Carcinoma and Thymic
      Neuroendocrine Tumors.
AB  - INTRODUCTION: Thymic carcinomas and thymic neuroendocrine tumors are rare
      diseases often treated with surgical resection. Currently, there are no
      guidelines regarding nodal dissection at the time of tumor resection. Moreover,
      the prognostic significance of nodal metastases is unclear. The goal of this
      study was to define the incidence and prognostic relevance of nodal metastases in
      patients with thymic carcinoma and thymic neuroendocrine tumors. METHODS: The
      Surveillance, Epidemiology and End Results database was queried for patients who
      underwent surgical resection of thymic carcinoma or a thymic neuroendocrine tumor
      with documented pathological examination of lymph nodes. The incidence of nodal
      metastases and the impact on survival were examined. RESULTS: We identified 176
      patients with thymic carcinoma and 53 with thymic neuroendocrine tumors. A median
      of three lymph nodes was sampled per patient. Positive metastasis to at least one
      lymph node was identified in 92 patients (40.2%). Nodal metastasis was more
      common in patients with thymic neuroendocrine tumors than in patients with thymic
      carcinoma (62.3% versus 33.5%). In multivariate analysis, nodal metastasis was
      more likely in patients with thymic neuroendocrine tumors and with more advanced
      tumors. The presence of nodal metastases had significant, independent, adverse
      impact on survival (hazard ratio, 2.933, 95% confidence interval, 1.903-4.521, p
      = 0.001). Median survival was 47 months in patients with nodal metastasis and 124
      months in patients without nodal metastases (p < 0.001). CONCLUSIONS: Nodal
      status seems to be an important prognostic factor in patients with thymic
      carcinoma and thymic neuroendocrine tumors. Nodal sampling should be performed
      during resection of these thymic malignancies.

PMID- 26317916
TI  - A New Prognostic Score Supporting Treatment Allocation for Multimodality Therapy
      for Malignant Pleural Mesothelioma: A Review of 12 Years' Experience.
AB  - INTRODUCTION: Treatment of malignant pleural mesothelioma (MPM) remains a
      clinical challenge. The aim of this study was to identify selection factors for
      allocation of MPM patients to multimodal therapy based on survival data from 12
      years of experience. METHODS: Eligible patients had MPM of all histological
      subtypes with clinical stage T1-3 N0-2 M0. Induction chemotherapy consisted of
      cisplatin/gemcitabine (cis/gem) or cisplatin/pemetrexed (cis/pem), followed by
      extrapleural pneumonectomy (EPP). Multivariate analysis was performed to assess
      independent prognosticators for overall survival (OS). A Multimodality Prognostic
      Score was developed based on clinical variables available before surgery.
      RESULTS: From May 1999 to August 2011, 186 MPM patients were intended to be
      treated with induction chemotherapy followed by EPP. Hematologic toxicity was
      significantly less frequent after cis/pem compared to cis/gem, but there was no
      difference in response or OS between the regimens. One hundred and twenty-eight
      patients underwent EPP with a 30-day mortality of 4.7%. Fifty-two percent of the
      patients received adjuvant radiotherapy. The median OS of patients undergoing EPP
      was significantly longer with 22 months (95% confidence interval: 20-24) when
      compared to 11 months (9-12) for patients treated without EPP. A prognostic score
      was defined considering tumor volume, histology, C-reactive protein level, and
      response to chemotherapy that identified patient groups not benefitting from
      multimodality treatment which was confirmed in an independent cohort. CONCLUSION:
      Patients receiving induction chemotherapy followed by EPP for MPM of all
      histological subtypes and irrespective of nodal status showed a median survival
      of 22 months. A prognostic score is proposed to help patient allocation for
      surgery after validation in an independent cohort.

PMID- 26317917
TI  - Impact of a Contralateral Tumor Nodule on Survival in Non-Small-Cell Lung Cancer.
AB  - INTRODUCTION: Contralateral lung tumors in non-small-cell lung cancer (NSCLC) are
      classified as stage M1a yet may represent hematogenous metastases or synchronous
      primary tumors. The impact of these tumors on overall survival (OS) is poorly
      understood. Here, we aim to determine whether NSCLC patients with M1a disease due
      only to a contralateral tumor nodule exhibit a favorable prognosis relative to
      other M1a or M1b patients. METHODS: Retrospective evaluation of the impact of
      contralateral tumor nodules on OS in NSCLC stratified by primary tumor size and N
      stage attained from Surveillance, Epidemiology, and End Results database.
      RESULTS: Of 173,640 patients, 5161 M1a-contra patients were identified. Median
      and 3-year OS for these patients exceeded that of patients with M1b (p < 0.0001)
      or other M1a disease (p < 0.0001). Primary tumor size and N stage were strongly
      associated with OS in M1a-contra patients. Three-year OS demonstrated a delayed
      convergence between M1a-contra and other M1a patients with primary tumors greater
      than or equal to 3 cm or mediastinal lymph node involvement. Proportional hazard
      modeling indicated that T1-2N0-1M1a-contra patients exhibit OS not significantly
      different (p = 0.258) from that predicted with comparable T and N stage disease
      plus a second early-stage primary. CONCLUSIONS: Contralateral tumors in NSCLC
      carry a more favorable prognosis than other M1a or M1b disease. Primary tumor
      size and N stage may help distinguish M1a-contra patients with hematogenous
      metastasis from those with a synchronous, second primary.

PMID- 26317918
TI  - Treatment and Prognosis of Isolated Local Relapse after Stereotactic Body
      Radiotherapy for Clinical Stage I Non-Small-Cell Lung Cancer: Importance of
      Salvage Surgery.
AB  - INTRODUCTION: Many efforts have been made to detect local relapse (LR) in the
      follow-up after stereotactic body radiotherapy (SBRT) for non-small-cell lung
      cancer (NSCLC) although limited data are available on its treatment and
      prognosis. We aimed to characterize treatment options and clarify long-term
      outcomes of isolated LR after SBRT for patients with clinical stage I NSCLC.
      METHODS: We reviewed our institutional database in search of patients with
      isolated LR after SBRT for clinical stage I NSCLC at our institution between 1999
      and 2013. Patient characteristics were compared with Mann-Whitney U test, chi2
      test, or Fisher's exact test as appropriate. Survival outcomes were estimated
      with Kaplan-Meier method. Potential prognostic factors were investigated using
      Cox proportional hazard model. RESULTS: Of 308 patients undergoing SBRT for
      clinical stage I NSCLC, 49 patients were identified to have isolated LR. Twelve
      patients underwent salvage surgery, none underwent radiotherapy, and eight
      patients received chemotherapy, whereas 29 patients received best supportive
      care. No patient characteristic except operability was significantly related with
      patient selection for LR treatments. Five-year overall survival (OS) rate of the
      whole cohort was 47.9% from SBRT and 25.7% from LR. Salvage surgery was
      associated with improved OS after LR (p = 0.014), and 5-year OS for patients
      undergoing salvage surgery was 79.5% from LR. CONCLUSIONS: It was confirmed that
      our patient selection for salvage surgery for isolated LR was associated with
      favorable survival outcomes. Operability based on multidisciplinary conferences,
      rather than measurable patient characteristics, is essential for appropriate
      patient selection for salvage surgery.

PMID- 26317919
TI  - Dissecting Pulmonary Large-Cell Carcinoma by Targeted Next Generation Sequencing
      of Several Cancer Genes Pushes Genotypic-Phenotypic Correlations to Emerge.
AB  - INTRODUCTION: Little is known about genotypic and phenotypic correlations in
      undifferentiated large-cell carcinoma (LCC) of the lung. METHODS: Thirty LCC were
      dissected by unsupervised targeted next generation sequencing analysis for 50
      cancer-associated oncogenes and tumor suppressor genes. Cell differentiation
      lineages were unveiled by using thyroid transcription factor-1 (TTF1) for
      adenocarcinoma (ADC) and p40 for squamous cell carcinoma (SQC), dichotomizing
      immunohistochemistry (IHC) results for TTF1 as negative or positive (whatever its
      extent) and for p40 as negative, positive, or focal (if <10% of reactive tumor
      cells). RESULTS: Three LCC were wild type (all TTF1+/p40-), whereas the remaining
      27 (90%) tumors had at least one gene mutation. Twenty-four cases featuring
      TTF1+/p40-, TTF1+/p40+/-, TTF1-/p40+/-, or TTF1-/p40- phenotypes comprised ATM,
      BRAF, CDKN2A, EGFR, ERBB4, FBXW7, FLT3, KRAS, NRAS, PIK3CA, PTPN11, RET, SMAD4,
      SMO, STK11, or TP53 mutations in keeping with ADC lineage, whereas three tumors
      showing TTF1-/p40+ phenotype harbored TP53 only and no ADC-related mutations in
      keeping with SQC lineage. Single, double, triple, quadruple, and quintuple
      mutations occurred in 16, 6, 2, 2, and 1 patient, respectively. The occurrence of
      three mutations or more but not any immunohistochemistry categorization predicted
      shorter overall survival (OS, p = 0.001) and disease-free survival (DFS, p =
      0.007), independent of age, sex, and tumor stage. CONCLUSIONS: Albeit preliminary
      also because of the relatively small number of LCC under evaluation, this
      targeted next generation sequencing study, however, revealed gene mutation
      heterogeneity in LCC with some genotypic-phenotypic correlations. Negativity or
      focal occurrence of p40 made SQC diagnosis unlikely on molecular grounds, but
      suggested ADC confirming validity of the axiom "no p40, no squamous."

PMID- 26317921
TI  - Leukocytes Don't Lie.

PMID- 26317926
TI  - Synthesis of Hindered alpha-Amino Carbonyls: Copper-Catalyzed Radical Addition
      with Nitroso Compounds.
AB  - The synthesis of sterically hindered anilines has been a significant challenge in
      organic chemistry. Here we report a Cu-catalyzed radical addition with in situ
      generated nitroso compounds to prepare sterically hindered amines directly from
      readily available materials. The transformation is conducted at room temperature,
      uses abundant copper salts, and is tolerant of a range of functional groups. 

PMID- 26317927
TI  - Genomic hallmarks of homologous recombination deficiency in invasive breast
      carcinomas.
AB  - Therapeutic strategies targeting Homologous Recombination Deficiency (HRD) in
      breast cancer requires patient stratification. The LST (Large-scale State
      Transitions) genomic signature previously validated for triple-negative breast
      carcinomas (TNBC) was evaluated as biomarker of HRD in luminal (hormone receptor
      positive) and HER2-overexpressing (HER2+) tumors. The LST genomic signature
      related to the number of large-scale chromosomal breakpoints in SNP-array tumor
      profile was applied to identify HRD in in-house and TCGA sets of breast tumors,
      in which the status of BRCA1/2 and other genes was also investigated. In the in
      house dataset, HRD was predicted in 5% (20/385) of sporadic tumors luminal or
      HER2+ by the LST genomic signature and the inactivation of BRCA1, BRCA2 or RAD51C
      confirmed this prediction in 75% (12/16) of the tested cases. In 14% (6/43) of
      tumors occurring in BRCA1/2 mutant carriers, the corresponding wild-type allele
      was retained emphasizing the importance of determining the tumor status. In the
      TCGA luminal and HER2+ subtypes HRD incidence was estimated at 5% (18/329, 95%CI:
      5-8%) and 2% (1/59, 95%CI: 2-9%), respectively. In TNBC cisplatin-based neo
      adjuvant clinical trials, HRD is shown to be a necessary condition for cisplatin
      sensitivity. This analysis demonstrates the high performance of the LST genomic
      signature for HRD detection in breast cancers, which suggests its potential as a
      biomarker for genetic testing and patient stratification for clinical trials
      evaluating platinum salts and PARP inhibitors. 

PMID- 26317928
TI  - Comparison of Major and Minor Viral SNPs Identified through Single Template
      Sequencing and Pyrosequencing in Acute HIV-1 Infection.
AB  - Massively parallel sequencing (MPS) technologies, such as 454-pyrosequencing,
      allow for the identification of variants in sequence populations at lower levels
      than consensus sequencing and most single-template Sanger sequencing experiments.
      We sought to determine if the greater depth of population sampling attainable
      using MPS technology would allow detection of minor variants in HIV founder virus
      populations very early in infection in instances where Sanger sequencing detects
      only a single variant. We compared single nucleotide polymorphisms (SNPs) during
      acute HIV-1 infection from 32 subjects using both single template Sanger and 454
      pyrosequencing. Pyrosequences from a median of 2400 viral templates per subject
      and encompassing 40% of the HIV-1 genome, were compared to a median of five
      individually amplified near full-length viral genomes sequenced using Sanger
      technology. There was no difference in the consensus nucleotide sequences over
      the 3.6kb compared in 84% of the subjects infected with single founders and 33%
      of subjects infected with multiple founder variants: among the subjects with
      disagreements, mismatches were found in less than 1% of the sites evaluated (of a
      total of nearly 117,000 sites across all subjects). The majority of the SNPs
      observed only in pyrosequences were present at less than 2% of the subject's
      viral sequence population. These results demonstrate the utility of the Sanger
      approach for study of early HIV infection and provide guidance regarding the
      design, utility and limitations of population sequencing from variable template
      sources, and emphasize parameters for improving the interpretation of massively
      parallel sequencing data to address important questions regarding target sequence
      evolution. 

PMID- 26317929
TI  - Saffold Virus, a Human Cardiovirus, and Risk of Persistent Islet Autoantibodies
      in the Longitudinal Birth Cohort Study MIDIA.
AB  - The aim of this study was to describe the frequency and distribution of Saffold
      virus in longitudinal stool samples from children, and test for association with
      development of persistent autoantibodies predictive of type 1 diabetes. A cohort
      of Norwegian children carrying the HLA genotype associated with highest risk of
      type 1 diabetes ("DR4-DQ8/DR3-DQ2") was followed with monthly stool samples from
      3 to 35 months of age. Blood samples were tested for autoantibodies to insulin,
      glutamic acid decarboxylase65 and Islet Antigen-2. 2077 stool samples from 27
      children with >= 2 repeatedly positive islet autoantibodies (cases), and 53
      matched controls were analysed for Saffold virus genomic RNA by semi-quantitative
      real-time reverse transcriptase PCR. Saffold virus was found in 53 of 2077 (2.6%)
      samples, with similar proportions between cases (2.5%) and controls (2.6%). The
      probability of being infected by 3 years of age was 28% (95% CI 0.18-0.40). Viral
      quantities ranged from <1 to almost 105 copies/MUl. Estimated odds ratio between
      islet autoimmunity and infection episodes prior to seroconversion was 1.98 (95%
      CI: 0.57-6.91, p = 0.29). Saffold virus had no statistically significant
      association with islet autoimmunity.

PMID- 26317968
TI  - Physical changes in the home environment to reduce television viewing and sugar
      sweetened beverage consumption among 5- to 12-year-old children: a randomized
      pilot study.
AB  - This study evaluated the feasibility of a home-based intervention to reduce sugar
      sweetened beverage intake and television viewing among children. Lower income
      parents of overweight children aged 5-12 years (n = 40) were randomized to a home
      environment intervention to reduce television viewing with locking devices and
      displace availability of sugar-sweetened beverages with home delivery of non
      caloric beverages (n = 25), or to a no-intervention control group (n = 15) for 6
      months. Data were collected at baseline and 6 months. After 6 months, television
      viewing hours per day was significantly lower in the intervention group compared
      with the control group (1.7 [SE = .02] vs. 2.6 [SE = .25] hours/day,
      respectively, P < .01). Sugar-sweetened beverage intake was marginally
      significantly lower among intervention group compared to control group children
      (0.21 [SE = .09] vs. 0.45 [SE = .10], respectively, P < .09). Body mass index
      (BMI) z-score was not significantly lower among intervention compared to control
      children. Among a lower income sample of children, a home-based intervention
      reduced television viewing, but not sugar-sweetened beverage intake or BMI z
      score.

PMID- 26317969
TI  - Absence of the Adaptor Protein PEA-15 Is Associated with Altered Pattern of Th
      Cytokines Production by Activated CD4+ T Lymphocytes In Vitro, and Defective Red
      Blood Cell Alloimmune Response In Vivo.
AB  - TCR-dependent and costimulation signaling, cell division, and cytokine
      environment are major factors driving cytokines expression induced by CD4(+) T
      cell activation. PEA-15 15 (Protein Enriched in Astrocyte / 15 kDa) is an adaptor
      protein that regulates death receptor-induced apoptosis and proliferation
      signaling by binding to FADD and relocating ERK1/2 to the cytosol, respectively.
      By using PEA-15-deficient mice, we examined the role of PEA-15 in TCR-dependent
      cytokine production in CD4(+) T cells. TCR-stimulated PEA-15-deficient CD4(+) T
      cells exhibited defective progression through the cell cycle associated with
      impaired expression of cyclin E and phosphoRb, two ERK1/2-dependent proteins of
      the cell cycle. Accordingly, expression of the division cycle-dependent cytokines
      IL-2 and IFNgamma, a Th1 cytokine, was reduced in stimulated PEA-15-deficient
      CD4(+) T cells. This was associated with abnormal subcellular
      compartmentalization of activated ERK1/2 in PEA-15-deficient T cells.
      Furthermore, in vitro TCR-dependent differentiation of naive CD4(+) CD62L(+) PEA
      15-deficient T cells was associated with a lower production of the Th2 cytokine,
      IL-4, whereas expression of the Th17-associated molecule IL4I1 was enhanced.
      Finally, a defective humoral response was shown in PEA-15-deficient mice in a
      model of red blood cell alloimmunization performed with Poly IC, a classical
      adjuvant of Th1 response in vivo. Collectively, our data suggest that PEA-15
      contributes to the specification of the cytokine pattern of activated Th cells,
      thus highlighting a potential new target to interfere with T cell functional
      polarization and subsequent immune response.

PMID- 26317970
TI  - Violence Affects Physical and Mental Health Differently: The General Population
      Based Tromso Study.
AB  - This general population-based study examined associations between violence and
      mental health, musculoskeletal pain, and early disability pension. The prevalence
      and consequences of good vs. poor adjustment (resilience vs. vulnerability)
      following encounters with violence were also examined. Data were based on the
      sixth wave of the "Tromso Study" (N = 12,981; 65.7% response rate, 53.4% women, M
      age = 57.5 years, SD-age = 12.7 years). Self-reported data on psychological
      (threats) and physical violence (beaten/kicked), mental health
      (anxiety/depression), musculoskeletal pain (MSP), and granting of disability
      pension (DP) were collected. Men suffered more violent events during childhood
      than women did, and vice versa during adulthood. Psychological violence implied
      poorer mental health and slightly more MSP than physical violence. The risk of
      MSP was highest for violence occurring during childhood in women and during the
      last year for men. A dose-response relationship between an increasing number of
      violent encounters and poorer health was observed. About 58% of individuals
      reported no negative impact of violence (hence, resilience group), whereas 42%
      considered themselves as more vulnerable following encounters with violence.
      Regression analyses indicated comparable mental health but slightly more MSP in
      the resilience group compared to the unexposed group, whereas the vulnerable
      group had significantly worse health overall and a higher risk of early granting
      of DP. Resilience is not an all-or-nothing matter, as physical ailments may
      characterize individuals adapting well following encounters with violence.

PMID- 26317971
TI  - Time Trends in Epidemiologic Characteristics and Imaging Features of Lung
      Adenocarcinoma: A Population Study of 21,113 Cases in China.
AB  - OBJECTIVES: This study aims to describe time trends of epidemiologic
      characteristics and imaging features over 14 years among histologically confirmed
      lung adenocarcinoma (ADC) in China and to discuss the possible reasons for these
      changes. MATERIALS AND METHODS: Data of 21,113 pathologically confirmed lung
      cancer patients from January 1999 to December 2012 were analyzed retrospectively.
      Preoperative high-resolution computer tomography (HRCT) images were available and
      reviewed in 5,439 lung ADC patients since 2005. Time trends of the ADC proportion
      of lung cancer cases, gender distribution, age at diagnosis, the proportion of
      early-stage ADC and imaging features were investigated. RESULTS: The proportion
      of ADC increased during the 14 years (P = 0.000). The ratio of female to male ADC
      cases was higher than both squamous cell carcinoma (SQCC) and total lung cancer
      cases (P = 0.000). The median age at diagnosis of ADC patients was younger than
      that of both SQCC and total lung cancer during the 14 years (P = 0.000). The
      proportion of age group 45-59 years increased in total lung cancer cases (P =
      0.000). When stratified by lung cancer histopathologic subtypes, this trend was
      also observed in ADC (P = 0.001) and SQCC (P = 0.007). The proportion of early
      stage cases of ADC increased from 2008 to 2012 (P < 0.001). The proportion of
      subsolid nodules (SSN) in ADC increased (P = 0.001) from 2005 to 2012.
      CONCLUSION: The data suggests that the proportion of ADC increased from 1999 to
      2012 especially in middle-aged, female patients; early-stage ADC and SSN on HRCT
      images gradually increased, which may have been caused by a change in smoking
      habits and increased application of HRCT.

PMID- 26317973
TI  - Pharmacokinetics of tecomin in rats after intragastric and intravenous
      administration.
AB  - The pharmacokinetics of tecomin, which is a potential bioactive compound from the
      flowers of Trollius chinensis, was studied. The results showed that this compound
      was easily absorbed and rapidly metabolized into veratric acid in vivo, and then
      the latter was eliminated slowly. In addition, the simulant in vitro
      gastrointestinal transformation experiments demonstrated that the basic enteral
      environment and intestinal bacterial flora also contributed to the metabolism of
      tecomin to veratric acid.

PMID- 26317972
TI  - Whole Genome-Sequencing and Phylogenetic Analysis of a Historical Collection of
      Bacillus anthracis Strains from Danish Cattle.
AB  - Bacillus anthracis, the causative agent of anthrax, is known as one of the most
      genetically monomorphic species. Canonical single-nucleotide polymorphism (SNP)
      typing and whole-genome sequencing were used to investigate the molecular
      diversity of eleven B. anthracis strains isolated from cattle in Denmark between
      1935 and 1988. Danish strains were assigned into five canSNP groups or lineages,
      i.e. A.Br.001/002 (n = 4), A.Br.Ames (n = 2), A.Br.008/011 (n = 2), A.Br.005/006
      (n = 2) and A.Br.Aust94 (n = 1). The match with the A.Br.Ames lineage is of
      particular interest as the occurrence of such lineage in Europe is demonstrated
      for the first time, filling an historical gap within the phylogeography of the
      lineage. Comparative genome analyses of these strains with 41 isolates from other
      parts of the world revealed that the two Danish A.Br.008/011 strains were related
      to the heroin-associated strains responsible for outbreaks of injection anthrax
      in drug users in Europe. Eight novel diagnostic SNPs that specifically
      discriminate the different sub-groups of Danish strains were identified and
      developed into PCR-based genotyping assays. 

PMID- 26317974
TI  - Decline in the Recovery from Synaptic Depression in Heavier Aplysia Results from
      Decreased Serotonin-Induced Novel PKC Activation.
AB  - The defensive withdrawal reflexes of Aplysia are important behaviors for
      protecting the animal from predation. Habituation and dishabituation allow for
      experience-dependent tuning of these reflexes and the mechanisms underlying these
      forms of behavioral plasticity involve changes in transmitter release from the
      sensory to motor neuron synapses through homosynaptic depression and the
      serotonin-mediated recovery from depression, respectively. Interestingly,
      dishabituation is reduced in older animals with no corresponding change in
      habituation. Here we show that the cultured sensory neurons of heavier animals
      (greater than 120 g) that form synaptic connections with motor neurons have both
      reduced recovery from depression and reduced novel PKC Apl II activation with
      5HT. The decrease in the recovery from depression correlated better with the size
      of the animal than the age of the animal. Much of this change in PKC activation
      and synaptic facilitation following depression can be rescued by direct
      activation of PKC Apl II with phorbol dibutyrate, suggesting a change in the
      signal transduction pathway upstream of PKC Apl II activation in the sensory
      neurons of larger animals.

PMID- 26317975
TI  - Gender Determinants of Vaccination Status in Children: Evidence from a Meta
      Ethnographic Systematic Review.
AB  - Using meta-ethnographic methods, we conducted a systematic review of qualitative
      research to understand gender-related reasons at individual, family, community
      and health facility levels why millions of children in low and middle income
      countries are still not reached by routine vaccination programmes. A systematic
      search of Medline, Embase, CINAHL, Cochrane Library, ERIC, Anthropological Lit,
      CSA databases, IBSS, ISI Web of Knowledge, JSTOR, Soc Index and Sociological
      Abstracts was conducted. Key words were built around the themes of immunization,
      vaccines, health services, health behaviour, and developing countries. Only
      papers, which reported on in-depth qualitative data, were retained. Twenty-five
      qualitative studies, which investigated barriers to routine immunisation, were
      included in the review. These studies were conducted between 1982 and 2012;
      eighteen were published after 2000. The studies represent a wide range of low- to
      middle income countries including some that have well known coverage challenges.
      We found that women's low social status manifests on every level as a barrier to
      accessing vaccinations: access to education, income, as well as autonomous
      decision-making about time and resource allocation were evident barriers.
      Indirectly, women's lower status made them vulnerable to blame and shame in case
      of childhood illness, partly reinforcing access problems, but partly increasing
      women's motivation to use every means to keep their children healthy. Yet in
      settings where gender discrimination exists most strongly, increasing
      availability and information may not be enough to reach the under immunised.
      Programmes must actively be designed to include mitigation measures to facilitate
      women's access to immunisation services if we hope to improve immunisation
      coverage. Gender inequality needs to be addressed on structural, community and
      household levels if the number of unvaccinated children is to substantially
      decrease. 

PMID- 26317976
TI  - Experience Changes How Emotion in Music Is Judged: Evidence from Children
      Listening with Bilateral Cochlear Implants, Bimodal Devices, and Normal Hearing.
AB  - Children using unilateral cochlear implants abnormally rely on tempo rather than
      mode cues to distinguish whether a musical piece is happy or sad. This led us to
      question how this judgment is affected by the type of experience in early
      auditory development. We hypothesized that judgments of the emotional content of
      music would vary by the type and duration of access to sound in early life due to
      deafness, altered perception of musical cues through new ways of using auditory
      prostheses bilaterally, and formal music training during childhood. Seventy-five
      participants completed the Montreal Emotion Identification Test. Thirty-three had
      normal hearing (aged 6.6 to 40.0 years) and 42 children had hearing loss and used
      bilateral auditory prostheses (31 bilaterally implanted and 11 unilaterally
      implanted with contralateral hearing aid use). Reaction time and accuracy were
      measured. Accurate judgment of emotion in music was achieved across ages and
      musical experience. Musical training accentuated the reliance on mode cues which
      developed with age in the normal hearing group. Degrading pitch cues through
      cochlear implant-mediated hearing induced greater reliance on tempo cues, but
      mode cues grew in salience when at least partial acoustic information was
      available through some residual hearing in the contralateral ear. Finally, when
      pitch cues were experimentally distorted to represent cochlear implant hearing,
      individuals with normal hearing (including those with musical training) switched
      to an abnormal dependence on tempo cues. The data indicate that, in a western
      culture, access to acoustic hearing in early life promotes a preference for mode
      rather than tempo cues which is enhanced by musical training. The challenge to
      these preferred strategies during cochlear implant hearing (simulated and real),
      regardless of musical training, suggests that access to pitch cues for children
      with hearing loss must be improved by preservation of residual hearing and
      improvements in cochlear implant technology. 

PMID- 26317978
TI  - The Usefulness of Defining Rapid Virological Response by a Very Sensitive Assay
      (TMA) during Treatment of HCV Genotype 2/3 Infection.
AB  - The aim of this study was to determine in patients with HCV genotype 2 or 3 the
      performance at week 4 of two assays with different sensitivities for HCV RNA
      detection, for the prediction of SVR and stratification for treatment duration
      (14 and 24 weeks). Recruitment was from two trials comparing 14 and 24 weeks
      treatment to patients with rapid virological response (RVR) (n = 550). RVR was
      originally defined as HCV RNA <50 IU/ml at week 4. Patients with an available
      frozen plasma sample drawn at week 4 and with follow-up data week 24 post
      treatment were included (n = 429). HCV-RNA was prospectively measured with COBAS
      Amplicor V2, Roche (CA) (lower detection limit 50 IU/ml) and retrospectively
      assessed with VERSANT HCV-RNA Qualitative Assay, Siemens (TMA) (lower limit
      detection 10 IU/ml). Genotype 3 was present in 80% and genotype 2 in 20%. A SVR
      was achieved in 82%. At week 4 HCV-RNA was undetectable in 74.8% and 63% of serum
      samples tested with CA and TMA, respectively. CA undetectable/TMA positive was
      observed in 61/341 (18%) of the samples. In genotype 3 patients a relapse was
      seen in 9% of the patients with both CA and TMA undetectable and in 25% of the
      patients who were CA undetectable/TMA positive (p = 0.006). In patients allocated
      to 14 weeks treatment a relapse was observed in 11% of TMA undetectable patients
      and 26% of TMA positive (p = 0.031). In genotype 2 patients treated for 14 weeks
      relapse was observed in 6% of the patients with both CA and TMA undetectable week
      4. Assays with high sensitivity for HCV RNA identifies patients at week 4 with
      high risk of virological relapse. We recommend that patients with genotype 3 and
      detectable HCV RNA at levels below 50 IU/ml do not receive truncated therapy with
      pegIFN and ribavirin. 

PMID- 26317977
TI  - Structural Analysis of the Regulatory Domain of ExsA, a Key Transcriptional
      Regulator of the Type Three Secretion System in Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa employs a type three secretion system to facilitate
      infections in mammalian hosts. The operons encoding genes of structural
      components of the secretion machinery and associated virulence factors are all
      under the control of the AraC-type transcriptional activator protein, ExsA. ExsA
      belongs to a unique subfamily of AraC-proteins that is regulated through protein
      protein contacts rather than small molecule ligands. Prior to infection, ExsA is
      inhibited through a direct interaction with the anti-activator ExsD. To activate
      ExsA upon host cell contact this interaction is disrupted by the anti
      antiactivator protein ExsC. Here we report the crystal structure of the
      regulatory domain of ExsA, which is known to mediate ExsA dimerization as well as
      ExsD binding. The crystal structure suggests two models for the ExsA dimer. Both
      models confirmed the previously shown involvement of helix alpha-3 in ExsA
      dimerization but one also suggest a role for helix alpha-2. These structural data
      are supported by the observation that a mutation in alpha-2 greatly diminished
      the ability of ExsA to activate transcription in vitro. Additional in vitro
      transcription studies revealed that a conserved pocket, used by AraC and the
      related ToxT protein for the binding of small molecule regulators, although
      present in ExsA is not involved in binding of ExsD. 

PMID- 26317979
TI  - Circulating Tumor Cells Enriched by the Depletion of Leukocytes with Bi
      Antibodies in Non-Small Cell Lung Cancer: Potential Clinical Application.
AB  - BACKGROUND: It has been considered that the detection methods for circulating
      tumor cells (CTCs) based on epithelial cell adhesion molecule (EpCAM)
      underestimate the number of CTCs and may miss a metastatic subpopulation with
      cancer stem cell (CSC) properties. Therefore, we investigated EpCAM-positive and 
      negative CTCs in non-small cell lung cancer (NSCLC) patients at different stages,
      assessed the clinical value of these CTCs and explored their capacity in the
      following CSC model. METHODS: CTCs were enriched by the depletion of leukocytes
      with bi-antibodies using a magnetic bead separation technique and then identified
      by the expression of EpCAM and cytokeratin 7 and 8 using multi-parameter flow
      cytometry. We determined the distribution of CTCs classified by the expression of
      EpCAM in 46 NSCLC patients with stages I to IV, assessed the diagnostic value of
      these CTCs by longitudinal monitoring in 4 index patients during adjuvant therapy
      and characterized the stemness of these CTCs by the expression of CXCR4 and CD133
      in 10 patients. RESULTS: EpCAM-negative (E-) CTCs were detected to be
      significantly higher than EpCAM-positive (E+) CTCs in stage IV (p = 0.003). The
      patients with the percentage of E-CTCs more than 95% (r > 95%) were detected to
      be significantly increased from 13.3% in stage I-II to 61.1% in stage IV (p =
      0.006). Kaplan-Meier analysis indicated that the patients with r > 95% had
      significantly shorter survival time than those with r <= 0.95 (p = 0.041).
      Longitudinal monitoring of CTCs indicated that the patients with a high
      percentage of E-CTCs in the blood were not responsive to either chemotherapy or
      targeted therapy. Further characterization of CTCs revealed that a stem-like
      subpopulation of CXCR4+CD133+ CTCs were detected to be significantly more
      prevalent in E-CTCs than that in E+CTCs (p = 0.005). CONCLUSIONS: The enrichment
      of CTCs by the depletion of leukocytes with bi-antibodies is a valuable method
      for estimating the number of CTCs, which can be potentially applied in predicting
      the prognosis, monitoring the therapeutic effect of NSCLC patients and further
      analyzing the biology of CTCs.

PMID- 26317982
TI  - Correction: The Neural Basis of Typewriting: A Functional MRI Study.

PMID- 26317980
TI  - Three Dimensional Culture of Human Renal Cell Carcinoma Organoids.
AB  - Renal cell carcinomas arise from the nephron but are heterogeneous in disease
      biology, clinical behavior, prognosis, and response to systemic therapy.
      Development of patient-specific in vitro models that efficiently and faithfully
      reproduce the in vivo phenotype may provide a means to develop personalized
      therapies for this diverse carcinoma. Studies to maintain and model tumor
      phenotypes in vitro were conducted with emerging three-dimensional culture
      techniques and natural scaffolding materials. Human renal cell carcinomas were
      individually characterized by histology, immunohistochemistry, and quantitative
      PCR to establish the characteristics of each tumor. Isolated cells were cultured
      on renal extracellular matrix and compared to a novel polysaccharide scaffold to
      assess cell-scaffold interactions, development of organoids, and maintenance of
      gene expression signatures over time in culture. Renal cell carcinomas cultured
      on renal extracellular matrix repopulated tubules or vessel lumens in renal
      pyramids and medullary rays, but cells were not observed in glomeruli or outer
      cortical regions of the scaffold. In the polysaccharide scaffold, renal cell
      carcinomas formed aggregates that were loosely attached to the scaffold or free
      floating within the matrix. Molecular analysis of cell-scaffold constructs
      including immunohistochemistry and quantitative PCR demonstrated that individual
      tumor phenotypes could be sustained for up to 21 days in culture on both
      scaffolds, and in comparison to outcomes in two-dimensional monolayer cultures.
      The use of three-dimensional scaffolds to engineer a personalized in vitro renal
      cell carcinoma model provides opportunities to advance understanding of this
      disease. 

PMID- 26317981
TI  - Effects of High-Intensity Interval Exercise versus Moderate Continuous Exercise
      on Glucose Homeostasis and Hormone Response in Patients with Type 1 Diabetes
      Mellitus Using Novel Ultra-Long-Acting Insulin.
AB  - INTRODUCTION: We investigated blood glucose (BG) and hormone response to aerobic
      high-intensity interval exercise (HIIE) and moderate continuous exercise (CON)
      matched for mean load and duration in type 1 diabetes mellitus (T1DM). MATERIAL
      AND METHODS: Seven trained male subjects with T1DM performed a maximal
      incremental exercise test and HIIE and CON at 3 different mean intensities below
      (A) and above (B) the first lactate turn point and below the second lactate turn
      point (C) on a cycle ergometer. Subjects were adjusted to ultra-long-acting
      insulin Degludec (Tresiba/ Novo Nordisk, Denmark). Before exercise, standardized
      meals were administered, and short-acting insulin dose was reduced by 25% (A),
      50% (B), and 75% (C) dependent on mean exercise intensity. During exercise, BG,
      adrenaline, noradrenaline, dopamine, cortisol, glucagon, and insulin-like growth
      factor-1, blood lactate, heart rate, and gas exchange variables were measured.
      For 24 h after exercise, interstitial glucose was measured by continuous glucose
      monitoring system. RESULTS: BG decrease during HIIE was significantly smaller for
      B (p = 0.024) and tended to be smaller for A and C compared to CON. No
      differences were found for post-exercise interstitial glucose, acute hormone
      response, and carbohydrate utilization between HIIE and CON for A, B, and C. In
      HIIE, blood lactate for A (p = 0.006) and B (p = 0.004) and respiratory exchange
      ratio for A (p = 0.003) and B (p = 0.003) were significantly higher compared to
      CON but not for C. CONCLUSION: Hypoglycemia did not occur during or after HIIE
      and CON when using ultra-long-acting insulin and applying our methodological
      approach for exercise prescription. HIIE led to a smaller BG decrease compared to
      CON, although both exercises modes were matched for mean load and duration, even
      despite markedly higher peak workloads applied in HIIE. Therefore, HIIE and CON
      could be safely performed in T1DM. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT02075567 http://www.clinicaltrials.gov/ct2/show/NCT02075567.

PMID- 26317983
TI  - Identifying Cognitive States Using Regularity Partitions.
AB  - Functional Magnetic Resonance (fMRI) data can be used to depict functional
      connectivity of the brain. Standard techniques have been developed to construct
      brain networks from this data; typically nodes are considered as voxels or sets
      of voxels with weighted edges between them representing measures of correlation.
      Identifying cognitive states based on fMRI data is connected with recording voxel
      activity over a certain time interval. Using this information, network and
      machine learning techniques can be applied to discriminate the cognitive states
      of the subjects by exploring different features of data. In this work we wish to
      describe and understand the organization of brain connectivity networks under
      cognitive tasks. In particular, we use a regularity partitioning algorithm that
      finds clusters of vertices such that they all behave with each other almost like
      random bipartite graphs. Based on the random approximation of the graph, we
      calculate a lower bound on the number of triangles as well as the expectation of
      the distribution of the edges in each subject and state. We investigate the
      results by comparing them to the state of the art algorithms for exploring
      connectivity and we argue that during epochs that the subject is exposed to
      stimulus, the inspected part of the brain is organized in an efficient way that
      enables enhanced functionality. 

PMID- 26317984
TI  - A Unimodal Model for Double Observer Distance Sampling Surveys.
AB  - Distance sampling is a widely used method to estimate animal population size.
      Most distance sampling models utilize a monotonically decreasing detection
      function such as a half-normal. Recent advances in distance sampling modeling
      allow for the incorporation of covariates into the distance model, and the
      elimination of the assumption of perfect detection at some fixed distance
      (usually the transect line) with the use of double-observer models. The
      assumption of full observer independence in the double-observer model is
      problematic, but can be addressed by using the point independence assumption
      which assumes there is one distance, the apex of the detection function, where
      the 2 observers are assumed independent. Aerially collected distance sampling
      data can have a unimodal shape and have been successfully modeled with a gamma
      detection function. Covariates in gamma detection models cause the apex of
      detection to shift depending upon covariate levels, making this model
      incompatible with the point independence assumption when using double-observer
      data. This paper reports a unimodal detection model based on a two-piece normal
      distribution that allows covariates, has only one apex, and is consistent with
      the point independence assumption when double-observer data are utilized. An
      aerial line-transect survey of black bears in Alaska illustrate how this method
      can be applied. 

PMID- 26317985
TI  - Diversity of Aquatic Pseudomonas Species and Their Activity against the Fish
      Pathogenic Oomycete Saprolegnia.
AB  - Emerging fungal and oomycete pathogens are increasingly threatening animals and
      plants globally. Amongst oomycetes, Saprolegnia species adversely affect wild and
      cultivated populations of amphibians and fish, leading to substantial reductions
      in biodiversity and food productivity. With the ban of several chemical control
      measures, new sustainable methods are needed to mitigate Saprolegnia infections
      in aquaculture. Here, PhyloChip-based community analyses showed that the
      Pseudomonadales, particularly Pseudomonas species, represent one of the largest
      bacterial orders associated with salmon eggs from a commercial hatchery. Among
      the Pseudomonas species isolated from salmon eggs, significantly more
      biosurfactant producers were retrieved from healthy salmon eggs than from
      Saprolegnia-infected eggs. Subsequent in vivo activity bioassays showed that
      Pseudomonas isolate H6 significantly reduced salmon egg mortality caused by
      Saprolegnia diclina. Live colony mass spectrometry showed that strain H6 produces
      a viscosin-like lipopeptide surfactant. This biosurfactant inhibited growth of
      Saprolegnia in vitro, but no significant protection of salmon eggs against
      Saprolegniosis was observed. These results indicate that live inocula of aquatic
      Pseudomonas strains, instead of their bioactive compound, can provide new
      (micro)biological and sustainable means to mitigate oomycete diseases in
      aquaculture. 

PMID- 26317986
TI  - An Enlarged Profile of Uremic Solutes.
AB  - Better knowledge of the uremic solutes that accumulate when the kidneys fail
      could lead to improved renal replacement therapy. This study employed the largest
      widely available metabolomic platform to identify such solutes. Plasma and plasma
      ultrafiltrate from 6 maintenance hemodialysis (HD) patients and 6 normal controls
      were first compared using a platform combining gas and liquid chromatography with
      mass spectrometry. Further studies compared plasma from 6 HD patients who had
      undergone total colectomy and 9 with intact colons. We identified 120 solutes as
      uremic including 48 that had not been previously reported to accumulate in renal
      failure. Combination of the 48 newly identified solutes with those identified in
      previous reports yielded an extended list of more than 270 uremic solutes. Among
      the solutes identified as uremic in the current study, 9 were shown to be colon
      derived, including 6 not previously identified as such. Literature search
      revealed that many uremic phenyl and indole solutes, including most of those
      shown to be colon-derived, come from plant foods. Some of these compounds can be
      absorbed directly from plant foods and others are produced by colon microbial
      metabolism of plant polyphenols that escape digestion in the small intestine. A
      limitation of the metabolomic method was that it underestimated the elevation in
      concentration of uremic solutes which were measured using more quantitative
      assays. 

PMID- 26317987
TI  - A Rapid Method to Characterize Mouse IgG Antibodies and Isolate Native Antigen
      Binding IgG B Cell Hybridomas.
AB  - B cell hybridomas are an important source of monoclonal antibodies. In this
      paper, we developed a high-throughput method to characterize mouse IgG antibodies
      using surface plasmon resonance technology. This assay rapidly determines their
      sub-isotypes, whether they bind native antigen and their approximate affinities
      for the antigen using only 50 MUl of hybridoma cell culture supernatant.
      Moreover, we found that mouse hybridomas secreting IgG antibodies also have
      membrane form IgG expression without Igalpha. Based on this surface IgG, we used
      flow cytometry to isolate rare gamma2a isotype switched variants from a gamma2b
      antibody secreting hybridoma cell line. Also, we used fluorescent antigen to
      single cell sort antigen binding hybridoma cells from bulk mixture of fused
      hybridoma cells instead of the traditional multi-microwell plate screening and
      limiting dilution sub-cloning thus saving time and labor. The IgG monoclonal
      antibodies specific for the native antigen identified with these methods are
      suitable for in vivo therapeutic uses, but also for sandwich ELISA assays,
      histology, flow cytometry, immune precipitation and x-ray crystallography. 

PMID- 26317988
TI  - Mortality Prediction in the Oldest Old with Five Different Equations to Estimate
      Glomerular Filtration Rate: The Health and Anemia Population-based Study.
AB  - BACKGROUND: Kidney function declines considerably with age, but little is known
      about its clinical significance in the oldest-old. OBJECTIVES: To study the
      association between reduced glomerular filtration rate (GFR) estimated according
      to five equations with mortality in the oldest-old. DESIGN: Prospective
      population-based study. SETTING: Municipality of Biella, Piedmont, Italy.
      PARTICIPANTS: 700 subjects aged 85 and older participating in the "Health and
      Anemia" Study in 2007-2008. MEASUREMENTS: GFR was estimated using five creatinine
      based equations: the Cockcroft-Gault (C-G), Modification of Diet in Renal Disease
      (MDRD), MAYO Clinic, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
      and Berlin Initiative Study-1 (BIS-1). Survival analysis was used to study
      mortality in subjects with reduced eGFR (<60 mL/min/1.73 m(2)) compared to
      subjects with eGFR >= 60 mL/min/1.73 m(2). RESULTS: Prevalence of reduced GFR was
      90.7% with the C-G, 48.1% with MDRD, 23.3% with MAYO, 53.6% with CKD-EPI and
      84.4% with BIS-1. After adjustment for confounders, two-year mortality was
      significantly increased in subjects with reduced eGFR using BIS-1 and C-G
      equations (adjusted HRs: 2.88 and 3.30, respectively). Five-year mortality was
      significantly increased in subjects with eGFR <60 mL/min/1.73 m(2) using MAYO,
      CKD-EPI and, in a graduated fashion in reduced eGFR categories, MDRD. After 5
      years, oldest old with an eGFR <30 mL/min/1.73 m(2) showed a significantly higher
      risk of death whichever equation was used (adjusted HRs between 2.04 and 2.70).
      CONCLUSION: In the oldest old, prevalence of reduced eGFR varies noticeably
      depending on the equation used. In this population, risk of mortality was
      significantly higher for reduced GFR estimated with the BIS-1 and C-G equations
      over the short term. Though after five years the MDRD appeared on the whole a
      more consistent predictor, differences in mortality prediction among equations
      over the long term were less apparent. Noteworthy, subjects with a severely
      reduced GFR were consistently at higher risk of death regardless of the equation
      used to estimate GFR.

PMID- 26317990
TI  - Total Synthesis and Biological Evaluation of Ipomoeassin F and Its Unnatural 11R
      Epimer.
AB  - Ipomoeassin F, a macrolide glycoresin containing an embedded disaccharide,
      possesses potent in vitro antitumor activity with an unknown mechanism of
      function. It inhibits tumor cell growth with single-digit nanomolar IC50 values,
      superior to many clinical chemotherapeutic drugs. To facilitate translation of
      its bioactivity into protein function for drug development, we report here a new
      synthesis for the gram-scale production of ipomoeassin F (3.8% over 17 linear
      steps) from commercially available starting materials. The conformation
      controlled subtle reactivity differences of the hydroxyl groups in carbohydrates
      were utilized to quickly construct the disaccharide core, which, along with
      judicial selection of protecting groups, made the current synthesis very
      efficient. The same strategy was also applied to the smooth preparation of the
      11R-epimer of ipomoeassin F for the first time. Cytotoxicity assays demonstrated
      the crucial role of the natural 11S configuration. In addition, cell cycle
      analyses and apoptosis assays on ipomoeassin F and/or its epimer were conducted.
      This work has laid a solid foundation for understanding the medicinal potential
      of the ipomoeassin family of glycolipids in the future. 

PMID- 26317989
TI  - Improving Assessment of Lipoprotein Profile in Type 1 Diabetes by 1H NMR
      Spectroscopy.
AB  - Patients with type 1 diabetes (T1D) present increased risk of cardiovascular
      disease (CVD). The aim of this study is to improve the assessment of lipoprotein
      profile in patients with T1D by using a robust developed method 1H nuclear
      magnetic resonance spectroscopy (1H NMR), for further correlation with clinical
      factors associated to CVD. Thirty patients with T1D and 30 non-diabetes control
      (CT) subjects, matched for gender, age, body composition (DXA, BMI, waist/hip
      ratio), regular physical activity levels and cardiorespiratory capacity
      (VO2peak), were analyzed. Dietary records and routine lipids were assessed. Serum
      lipoprotein particle subfractions, particle sizes, and cholesterol and
      triglycerides subfractions were analyzed by 1H NMR. It was evidenced that
      subjects with T1D presented lower concentrations of small LDL cholesterol, medium
      VLDL particles, large VLDL triglycerides, and total triglycerides as compared to
      CT subjects. Women with T1D presented a positive association with HDL size
      (p<0.005; R = 0.601) and large HDL triglycerides (p<0.005; R = 0.534) and
      negative (p<0.005; R = -0.586) to small HDL triglycerides. Body fat composition
      represented an important factor independently of normal BMI, with large LDL
      particles presenting a positive correlation to total body fat (p<0.005; R =
      0.505), and total LDL cholesterol and small LDL cholesterol a positive
      correlation (p<0.005; R = 0.502 and R = 0.552, respectively) to abdominal fat in
      T1D subjects; meanwhile, in CT subjects, body fat composition was mainly
      associated to HDL subclasses. VO2peak was negatively associated (p<0.005; R = 
      0.520) to large LDL-particles only in the group of patients with T1D. In
      conclusion, patients with T1D with adequate glycemic control and BMI and without
      chronic complications presented a more favourable lipoprotein profile as compared
      to control counterparts. In addition, slight alterations in BMI and/or body fat
      composition showed to be relevant to provoking alterations in lipoproteins
      profiles. Finally, body fat composition appears to be a determinant for
      cardioprotector lipoprotein profile. 

PMID- 26317991
TI  - Comparison of Rebound Tonometry, Perkins Applanation Tonometry and Ocular
      Response Analyser in Mucopolysaccharidosis Patients.
AB  - AIMS: To investigate the feasibility and to compare three devices measuring
      intraocular pressure (IOP) in mucopolysaccharidosis patients (MPS): iCare rebound
      tonometer (RT), Perkins applanation tonometer (PAT) and ocular response analyzer
      (ORA). METHODS: MPS patients who underwent at least two examinations out of: RT,
      PAT and ORA at the same visit were identified and retrospectively analyzed in
      this study. RESULTS: 17 patients fulfilled the inclusion criterion. In all 17
      patients IOP measurements were performed with RT (34 eyes) and ORA (33 eyes),
      while PAT measurement was possible in only 12 (24 eyes) patients. The RT, corneal
      compensated intraocular pressure (IOPcc) and Goldmann-correlated intraocular
      pressure (IOPg) differed relevantly from IOP assessed with PAT. Corneal clouding
      in MPS patients correlated positively with PAT, RT and IOPg (r = 0.3, 0.5, and
      0.5 respectively), but not with IOPcc (r = 0.07). The MPS-related corneal
      clouding correlated positively with biomechanical corneal parameters assessed
      with ORA: corneal hysteresis (r = 0.77) and corneal resistance factor (r = 0.77)
      either. CONCLUSIONS: RT and ORA measurements were tolerated better than
      applanation tonometry in MPS patients. IOP measurements assessed with RT and ORA
      differed relevantly from PAT. Corneal-compensated IOP assessed with ORA seems to
      be less affected by the MPS-related corneal clouding than applanation or rebound
      tonometry. RT and ORA measurements should be preferred for IOP assessment in
      patients with MPS.

PMID- 26317992
TI  - Macular Bruch's Membrane Length and Axial Length. The Beijing Eye Study.
AB  - PURPOSE: To assess whether macular Bruch's membrane gets lengthened in axial
      myopia. METHODS: Using the enhanced depth imaging mode of spectral-domain optical
      coherence tomography and examining a subgroup of participants of the population
      based cross-sectional Beijing Eye Study, we measured the length of Bruch's
      membrane ("MacBMLength") from the fovea to the temporal edge of parapapillary
      gamma zone, and the distance between the fovea and the temporal optic disc
      border. Parapapillary gamma zone was defined as the parapapillary region without
      Bruch's membrane. We additionally measured ocular biometric parameters and
      assessed non-ophthalmologic variables. RESULTS: Measurements of MacBMLength were
      performed on 322 individuals. MacBMLength (mean: 3.99 +/- 0.33 mm; range: 3.17
      4.93 mm) was not significantly associated with any systemic parameter or ocular
      biometric parameter. Gamma zone width (mean: 0.18 +/- 0.30 mm; range: 0.00-2.61
      mm) was associated (multivariate analysis; correlation coefficient r:0.80) with
      longer axial length (P<0.001; standardized correlation coefficient beta: 0.60;
      non-standardized correlation coefficient B:0.11; 95%CI: 0.09,0.14) and with
      longer fovea-optic disc border distance (P<0.001; beta:0.28; B:0.19;
      95%CI:0.14,0.25), but not with MacBMLength (P = 0.42). Fovea-temporal disc border
      distance (mean: 4.16 +/- 0.44 mm; range: 3.17-5.86 mm) was associated (overall
      correlation coefficient: 0.68) with longer axial length (P<0.001; beta: 0.36; B:
      0.10; 95%CI: 0.06, 0.13), after adjusting for flatter anterior chamber depth (P =
      0.003; beta:-0.14; B:-0.14; 95%CI: -0.23,-0.05) and wider parapapillary gamma
      zone (P<0.001; beta:0.42; B:0.62; 95%CI:0.44,0.81). CONCLUSIONS: In contrast to
      parapapillary gamma zone width and fovea-disc border distance, MacBMLength was
      not significantly associated with axial length. Axial elongation associated
      increase in fovea-disc distance may predominantly occur through development or
      elongation of parapapillary gamma zone, while macular Bruch's membrane may mostly
      be independent of axial elongation.

PMID- 26317993
TI  - Advantages of collecting multiple urinary iodine concentrations when assessing
      iodine status of a population.
AB  - AIM: To evaluate the effect of collecting multiple (four) urine samples on the
      extensive variance often observed within a cohort when determining iodine status
      via urinary iodine concentration (UIC). METHODS: Fifty-one children aged two to
      three years and thirty children aged 8-10 years participated in the study in
      South East Queensland, Australia. Each child's four urine samples were analysed
      using ammonium persulphate digestion before a Sandell-Kolthoff reaction method.
      Analysis of variance techniques were used to assess the effect of using multiple
      urine samples. RESULTS: The median UICs were 223.3 and 141 MUg/L for two- to
      three-year-olds and eight- to 10-year-olds, respectively. The coefficient of
      variance (CV) of UIC for children aged two to three years was reduced by 35.6%,
      36.5% and 39.7% when two, three and four samples were included in the adjustment,
      respectively. Similarly, the CV of UIC for children aged 8-10 years was reduced
      by 24.7%, 30.7% and 34.7%, respectively. CONCLUSION: Although the practicality
      and cost of collecting multiple UICs need to be considered, collecting multiple
      UIC samples from each participant provides a more accurate reflection of a cohort
      iodine status.

PMID- 26317994
TI  - The Relationship between Gene Network Structure and Expression Variation among
      Individuals and Species.
AB  - Variation among individuals is a prerequisite of evolution by natural selection.
      As such, identifying the origins of variation is a fundamental goal of biology.
      We investigated the link between gene interactions and variation in gene
      expression among individuals and species using the mammalian limb as a model
      system. We first built interaction networks for key genes regulating early
      (outgrowth; E9.5-11) and late (expansion and elongation; E11-13) limb development
      in mouse. This resulted in an Early (ESN) and Late (LSN) Stage Network.
      Computational perturbations of these networks suggest that the ESN is more
      robust. We then quantified levels of the same key genes among mouse individuals
      and found that they vary less at earlier limb stages and that variation in gene
      expression is heritable. Finally, we quantified variation in gene expression
      levels among four mammals with divergent limbs (bat, opossum, mouse and pig) and
      found that levels vary less among species at earlier limb stages. We also found
      that variation in gene expression levels among individuals and species are
      correlated for earlier and later limb development. In conclusion, results are
      consistent with the robustness of the ESN buffering among-individual variation in
      gene expression levels early in mammalian limb development, and constraining the
      evolution of early limb development among mammalian species. 

PMID- 26317995
TI  - Glycemic Control with Thiazolidinedione Is Associated with Fracture of T2DM
      Patients.
AB  - OBJECTIVE: Diabetes is a common diseases and a major problem worldwide. Diabetic
      osteopathy might be elevated in diabetic patients and is usually caused by bone
      fracture. Several diabetes medications, such as thiazolidinediones (TZDs), could
      lead to increased risks of fracture. METHODS: We used the nationwide database to
      identified 32466 patients who had developed type 2 diabetes from 2000 to 2010 as
      the diabetic cohort and, from that group, we selected 3427 diabetic patients who
      had developed bone fracture to survey the possible risk factors, includng
      commonly used diabetes medication. RESULTS: We found that TZDs might present
      increased risks for fracture in patients who used it for an extended period (7 to
      730 days before the index date), especially in female patients younger than 64
      years old, for whom the risk was elevated from a 1.74- to a 2.58-fold odds ratio.
      CONCLUSIONS: We recommend that clinics follow up with non-osteoporotic female
      patients younger than 64 years old who are using TZDs, to avoid the associated
      risks of fracture.

PMID- 26317996
TI  - Do "birds of a feather flock together" or do "opposites attract"? Behavioral
      responses and temperament predict success in pairings of rhesus monkeys in a
      laboratory setting.
AB  - The growing recognition that social needs of primates in captivity must be
      addressed can present challenges to staff at primate facilities charged with
      implementing pair-housing solutions for animals. Unfortunately, there are few
      published papers that identify individual characteristics that might facilitate
      the social pairing process, and those that have looked at pre-pairing measures of
      behavior have produced mixed results. Using a database of n = 340 isosexual
      pairing attempts, we report that measures associated with responses to a
      standardized infant assessment protocol (the BioBehavioral Assessment program)
      predict success in pairing attempts that occurred years later. Behavioral
      responses to a brief separation and relocation, to a human intruder challenge, as
      well as ratings of temperament, were obtained from rhesus monkeys at 3-4 months
      of age. Logistic regression was used to identify potential predictors of success
      when animals were paired up to 10 years after the behavioral assessments. Among
      females, success was higher when members of a pair were more similar (i.e., a
      smaller difference scores) in patterns of emotional responding (Emotionality,
      Nervous temperament) during the infant assessments. In contrast, among males,
      success was higher when the pair had lower mean values for Gentle and Nervous
      temperament scores; when the members were younger; when pairs had a greater
      weight difference; and when they came from the same rearing background. Together,
      our results suggest that broad measures reflecting patterns of emotionality in
      response to challenge, which can be assessed in infancy (but which remain
      relatively stable throughout life) can be usefully employed to increase the
      likelihood of success in pairing attempts. Am. J. Primatol. 79:e22464, 2017. (c)
      2015 Wiley Periodicals, Inc.

PMID- 26317997
TI  - Inhibition of mTORC1 Enhances the Translation of Chikungunya Proteins via the
      Activation of the MnK/eIF4E Pathway.
AB  - Chikungunya virus (CHIKV), the causative agent of a major epidemic spanning five
      continents, is a positive stranded mRNA virus that replicates using the cell's
      cap-dependent translation machinery. Despite viral infection inhibiting mTOR, a
      metabolic sensor controls cap-dependent translation, viral proteins are
      efficiently translated. Rapalog treatment, silencing of mtor or raptor genes, but
      not rictor, further enhanced CHIKV infection in culture cells. Using biochemical
      assays and real time imaging, we demonstrate that this effect is independent of
      autophagy or type I interferon production. Providing in vivo evidence for the
      relevance of our findings, mice treated with mTORC1 inhibitors exhibited
      increased lethality and showed a higher sensitivity to CHIKV. A systematic
      evaluation of the viral life cycle indicated that inhibition of mTORC1 has a
      specific positive effect on viral proteins, enhancing viral replication by
      increasing the translation of both structural and nonstructural proteins.
      Molecular analysis defined a role for phosphatidylinositol-3 kinase (PI3K) and
      MAP kinase-activated protein kinase (MnKs) activation, leading to the hyper
      phosphorylation of eIF4E. Finally, we demonstrated that in the context of CHIKV
      inhibition of mTORC1, viral replication is prioritized over host translation via
      a similar mechanism. Our study reveals an unexpected bypass pathway by which
      CHIKV protein translation overcomes viral induced mTORC1 inhibition. 

PMID- 26317998
TI  - SIRT3 inhibits prostate cancer by destabilizing oncoprotein c-MYC through
      regulation of the PI3K/Akt pathway.
AB  - SIRT3 is involved in aging-related diseases including cancer, but its role in
      prostate cancer and detailed regulatory function are not known. We found that
      SIRT3 was moderately down-regulated in prostate carcinomas. Overexpression of
      SIRT3 by lentiviral transfection inhibited prostate cancer growth both in vitro
      and in vivo, whereas knockdown of SIRT3 increased prostate tumor growth.
      Mechanistically, the tumor suppression effect of SIRT3 was achieved via its
      inhibition of the PI3K/Akt pathway. Notably, upregulation of SIRT3 suppressed the
      phosphorylation of Akt, leading to the ubiquitination and degradation of
      oncoprotein c-MYC; this could be attenuated by constitutive activation of
      PI3K/Akt signaling. Collectively, our results unveiled SIRT3's tumor suppressive
      function and the underlying mechanism in prostate cancer, which might provide
      therapeutic implications for the disease. 

PMID- 26317999
TI  - Conformal Pad-Printing Electrically Conductive Composites onto Thermoplastic
      Hemispheres: Toward Sustainable Fabrication of 3-Cents Volumetric Electrically
      Small Antennas.
AB  - Electrically small antennas (ESAs) are becoming one of the key components in the
      compact wireless devices for telecommunications, defence, and aerospace systems,
      especially for the spherical one whose geometric layout is more closely
      approaching Chu's limit, thus yielding significant bandwidth improvements
      relative to the linear and planar counterparts. Yet broad applications of the
      volumetric ESAs are still hindered since the low cost fabrication has remained a
      tremendous challenge. Here we report a state-of-the-art technology to transfer
      electrically conductive composites (ECCs) from a planar mould to a volumetric
      thermoplastic substrate by using pad-printing technology without pattern
      distortion, benefit from the excellent properties of the ECCs as well as the
      printing-calibration method that we developed. The antenna samples prepared in
      this way meet the stringent requirement of an ESA (ka is as low as 0.32 and the
      antenna efficiency is as high as 57%), suggesting that volumetric electronic
      components i.e. the antennas can be produced in such a simple, green, and cost
      effective way. This work can be of interest for the development of studies on
      green and high performance wireless communication devices. 

PMID- 26318000
TI  - EPR-Spin Trapping and Flow Cytometric Studies of Free Radicals Generated Using
      Cold Atmospheric Argon Plasma and X-Ray Irradiation in Aqueous Solutions and
      Intracellular Milieu.
AB  - Electron paramagnetic resonance (EPR)-spin trapping and flow cytometry were used
      to identify free radicals generated using argon-cold atmospheric plasma (Ar-CAP)
      in aqueous solutions and intracellularly in comparison with those generated by X
      irradiation. Ar-CAP was generated using a high-voltage power supply unit with low
      frequency excitation. The characteristics of Ar-CAP were estimated by vacuum UV
      absorption and emission spectra measurements. Hydroxyl (.OH) radicals and
      hydrogen (H) atoms in aqueous solutions were identified with the spin traps 5,5
      dimethyl-1-pyrroline N-oxide (DMPO), 3,3,5,5-tetramethyl-1-pyrroline-N-oxide
      (M4PO), and phenyl N-t-butylnitrone (PBN). The occurrence of Ar-CAP-induced
      pyrolysis was evaluated using the spin trap 3,5-dibromo-4-nitrosobenzene
      sulfonate (DBNBS) in aqueous solutions of DNA constituents, sodium acetate, and L
      alanine. Human lymphoma U937 cells were used to study intracellular oxidative
      stress using five fluorescent probes with different affinities to a number of
      reactive species. The analysis and quantification of EPR spectra revealed the
      formation of enormous amounts of .OH radicals using Ar-CAP compared with that by
      X-irradiation. Very small amounts of H atoms were detected whereas nitric oxide
      was not found. The formation of .OH radicals depended on the type of rare gas
      used and the yield correlated inversely with ionization energy in the order of
      krypton > argon = neon > helium. No pyrolysis radicals were detected in aqueous
      solutions exposed to Ar-CAP. Intracellularly, .OH, H2O2, which is the
      recombination product of .OH, and OCl- were the most likely formed reactive
      oxygen species after exposure to Ar-CAP. Intracellularly, there was no practical
      evidence for the formation of NO whereas very small amounts of superoxides were
      formed. Despite the superiority of Ar-CAP in forming .OH radicals, the exposure
      to X-rays proved more lethal. The mechanism of free radical formation in aqueous
      solutions and an intracellular milieu is discussed. 

PMID- 26318002
TI  - The Effect of Long-Distance Transportation on the Fitness of Irradiated False
      Codling Moth (Lepidoptera: Tortricidae) for Use in a Sterile Insect Release
      Program.
AB  - The effect of cold immobilization and long-distance transport of irradiated
      Thaumatotibia leucotreta (Meyrick) on the flight ability of male (?) and female
      (?) moths, the longevity of male and female moths, and the realized fecundity of
      mating pairs CIM (chilled irradiated moths) ? * CIM?, CIM? * NIP (nonirradiated
      pupae) ?, NIP? * CIM?, and NIP? * NIP? was examined to improve application of the
      sterile insect technique (SIT). Adult moths treated with 150 Gy of gamma
      radiation were immobilized with cold temperature between 4 and 6 degrees C inside
      a polyurethane cooler box and transported for 12 h by road from Citrusdal,
      Western Cape Province, to Addo, Eastern Cape Province. Nonirradiated moths were
      transported as pupae inside a cardboard tray and removed by hand after which male
      and female pupae were separated and placed inside containers for eclosion. Male
      and female moths were individually placed inside petri dishes to determine
      longevity or paired with irradiated and nonirradiated counterparts to evaluate
      realized fecundity before incubation in 100% darkness at 25 degrees C and 75%
      relative humidity. Flight tests were conducted indoors at 25 degrees C by release
      of individual moths per hand. A significant decrease in flight ability and
      longevity of irradiated false codling moth was found after handling, cold
      immobilization, and transport, although critically, realized fecundity was not
      affected. Because of the impact of long-distance transport on quality of the
      released insects as well as the efficacy of SIT, comprehensive protocols for this
      critical step in the process need to be developed for a pestiferous insect with
      phytosanitary status such as false codling moth. 

PMID- 26318001
TI  - Comparative Genomic, MicroRNA, and Tissue Analyses Reveal Subtle Differences
      between Non-Diabetic and Diabetic Foot Skin.
AB  - Diabetes Mellitus (DM) is a chronic, severe disease rapidly increasing in
      incidence and prevalence and is associated with numerous complications. Patients
      with DM are at high risk of developing diabetic foot ulcers (DFU) that often lead
      to lower limb amputations, long term disability, and a shortened lifespan.
      Despite this, the effects of DM on human foot skin biology are largely unknown.
      Thus, the focus of this study was to determine whether DM changes foot skin
      biology predisposing it for healing impairment and development of DFU. Foot skin
      samples were collected from 20 patients receiving corrective foot surgery and,
      using a combination of multiple molecular and cellular approaches, we performed
      comparative analyses of non-ulcerated non-neuropathic diabetic foot skin (DFS)
      and healthy non-diabetic foot skin (NFS). MicroRNA (miR) profiling of laser
      captured epidermis and primary dermal fibroblasts from both DFS and NFS samples
      identified 5 miRs de-regulated in the epidermis of DFS though none reached
      statistical significance. MiR-31-5p and miR-31-3p were most profoundly induced.
      Although none were significantly regulated in diabetic fibroblasts, miR-29c-3p
      showed a trend of up-regulation, which was confirmed by qPCR in a prospective set
      of 20 skin samples. Gene expression profiling of full thickness biopsies
      identified 36 de-regulated genes in DFS (>2 fold-change, unadjusted p-value <=
      0.05). Of this group, three out of seven tested genes were confirmed by qPCR:
      SERPINB3 was up-regulated whereas OR2A4 and LGR5 were down-regulated in DFS.
      However no morphological differences in histology, collagen deposition, and
      number of blood vessels or lymphocytes were found. No difference in proliferative
      capacity was observed by quantification of Ki67 positive cells in epidermis.
      These findings suggest DM causes only subtle changes to foot skin. Since
      morphology, mRNA and miR levels were not affected in a major way, additional
      factors, such as neuropathy, vascular complications, or duration of DM, may
      further compromise tissue's healing ability leading to development of DFUs. 

PMID- 26318003
TI  - Efficiency of Trapping Systems for Detecting Tuta absoluta (Lepidoptera:
      Gelechiidae).
AB  - Tuta absoluta Meyrick (Lepidoptera: Gelechiidae), a pest of tomato, was recently
      detected in Panama in Central America and now threatens to expand into the
      important tomato production areas of Mexico and the United States. Moths caught
      in T. absoluta pheromone-baited traps must be removed and dissected to confirm
      the species present before containment and mitigation strategies are put in
      place. Timely processing of traps can be hindered by the presence of numerous
      similar nontarget moths that cannot be easily prescreened. Trapping systems using
      dry bucket traps or Delta traps with either hot melt pressure sensitive adhesives
      (HMPSA) or cool melt adhesives were evaluated for their effectiveness in trapping
      T. absoluta and for their ease in allowing identification of nontarget moths.
      Delta traps in Panama with HMPSA and cool melt adhesives both trapped T. absoluta
      with equal efficacy. In Florida, nontarget moths were easier to prescreen from
      bucket traps and HMPSA inserts. Importantly, moths found in bucket traps as well
      as on cool melt adhesive inserts were of a lower quality than those on HMPSA
      inserts, making identification more difficult. Studies conducted in Florida and
      Panama tomato and potato fields showed that commercially produced pheromones
      containing only the main pheromone component ((3E, 8Z, 11Z)-tetradecatrien-1-yl
      acetate) or containing both the main and minor pheromone component ((3E, 8Z)
      tetradecadien-1-yl) attracted nontarget moths. Survey programs, particularly
      large-scale ones, should consider the application of alternative trapping systems
      or new adhesives available in order to facilitate the visual prescreening of
      nontarget moths. 

PMID- 26318004
TI  - Effects of Oral Exposure to Fungicides on Honey Bee Nutrition and Virus Levels.
AB  - Sublethal exposure to fungicides can affect honey bees (Apis mellifera L.) in
      ways that resemble malnutrition. These include reduced brood rearing, queen loss,
      and increased pathogen levels. We examined the effects of oral exposure to the
      fungicides boscalid and pyraclostrobin on factors affecting colony nutrition and
      immune function including pollen consumption, protein digestion, hemolymph
      protein titers, and changes in virus levels. Because the fungicides are
      respiratory inhibitors, we also measured ATP concentrations in flight muscle. The
      effects were evaluated in 3- and 7-d-old worker bees at high fungicide
      concentrations in cage studies, and at field-relevant concentrations in colony
      studies. Though fungicide levels differed greatly between the cage and colony
      studies, similar effects were observed. Hemolymph protein concentrations were
      comparable between bees feeding on pollen with and without added fungicides.
      However, in both cage and colony studies, bees consumed less pollen containing
      fungicides and digested less of the protein. Bees fed fungicide-treated pollen
      also had lower ATP concentrations and higher virus titers. The combination of
      effects we detected could produce symptoms that are similar to those from poor
      nutrition and weaken colonies making them more vulnerable to loss from additional
      stressors such as parasites and pathogens. 

PMID- 26318005
TI  - Phytosanitation Methods Influence Posttreatment Colonization of Juglans nigra
      Logs by Pityophthorus juglandis (Coleoptera: Curculionidae: Scolytinae).
AB  - Several North American walnut species (Juglans spp.) are threatened by thousand
      cankers disease which is caused by the walnut twig beetle (Pityophthorus
      juglandis Blackman) and its associated fungal plant pathogen, Geosmithia morbida
      M. Kolarik, E. Freeland, C. Utley and N. Tisserat sp. nov. Spread of this disease
      may occur via movement of infested black walnut (Juglans nigra L.) wood. This
      study evaluated the ability of P. juglandis to colonize J. nigra wood previously
      treated with various phytosanitation methods. Steam-heated and methyl bromide
      fumigated J. nigra logs, as well as kiln-dried natural wane J. nigra lumber (with
      and without bark) were subsequently exposed to P. juglandis colonization pressure
      in two exposure scenarios. Following a pheromone-mediated, high-pressure scenario
      in the canopy of infested trees, beetles readily colonized the bark of steam
      heated and methyl bromide-fumigated logs, and were also recovered from kiln-dried
      lumber on which a thin strip of bark was retained. In the simulated lumberyard
      exposure experiment, during which samples were exposed to lower P. juglandis
      populations, beetles were again recovered from bark-on steam-heated logs, but
      were not recovered from kiln-dried bark-on lumber. These data suggest logs and
      bark-on lumber treated with phytosanitation methods should not be subsequently
      exposed to P. juglandis populations. Further beetle exclusion efforts for
      phytosanitized, bark-on walnut wood products transported out of quarantined areas
      may be necessary to ensure that these products do not serve as a pathway for the
      spread of P. juglandis and thousand cankers disease. 

PMID- 26318006
TI  - Bt Maize Seed Mixtures for Helicoverpa zea (Lepidoptera: Noctuidae): Larval
      Movement, Development, and Survival on Non-transgenic Maize.
AB  - In 2012 and 2013, field trials were conducted near Rosemount, MN, to assess the
      movement and development of Helicoverpa zea (Boddie) larvae on non-Bt refuge corn
      plants within a seed mixture of non-Bt and Bt corn. The Bt corn hybrid expressed
      three Bt toxins-Cry1Ab, Cry1F, and Vip3A. As the use of seed mixtures for insect
      resistance management (IRM) continues to be implemented, it is necessary to
      further characterize how this IRM approach impacts resistance development in ear
      feeding Lepidopteran pests. The potential for Bt pollen movement and cross
      pollination of the non-Bt ears in a seed mixture may lead to Bt toxin exposure to
      larvae developing on those refuge ears. Larval movement and development by H.
      zea, feeding on non-Bt refuge plants adjacent to either transgenic Bt or non-Bt
      plants, were measured to investigate the potential for unintended Bt exposure.
      Non-Bt plants were infested with H. zea eggs and subplots were destructively
      sampled twice per week within each treatment to assess larval development,
      location, and kernel injury. Results indicate that H. zea larval movement between
      plants is relatively low, ranging from 2-16% of larvae, and occurs mainly after
      reaching the second instar. Refuge plants in seed mixtures did not produce
      equivalent numbers of H. zea larvae, kernel injury, and larval development
      differed as compared with a pure stand of non-Bt plants. This suggests that there
      may be costs to larvae developing on refuge plants within seed mixtures and
      additional studies are warranted to define potential impacts. 

PMID- 26318007
TI  - Molecular Identification of Helicoverpa armigera (Lepidoptera: Noctuidae:
      Heliothinae) in Argentina and Development of a Novel PCR-RFLP Method for its
      Rapid Differentiation From H. zea and H. gelotopoeon.
AB  - Helicoverpa armigera (Hubner) (Lepidoptera: Noctuidae: Heliothinae) is among the
      most voracious global pests of agriculture. Adults of this species were
      identified recently in northern Argentina by dissection of male genitalia. In
      this work, a rapid and simple molecular tool was designed to distinguish H.
      armigera from the morphologically similar indigenous bollworms Helicoverpa zea
      (Boddie) and Helicoverpa gelotopoeon (Dyar), regardless of the life stage.
      Amplification of partial COI gene with a new primer pair, and subsequent
      digestion with endonuclease HinfI, yielded different RFLP profiles for the three
      main Helicoverpa pests currently present in South America. The method was
      validated in Helicoverpa specimens collected across Argentina, whose identity was
      further corroborated by COI sequencing and phylogenetic analysis. The data
      reported here constitute the first molecular confirmation of this pest in the
      country. The survey revealed the occurrence of H. armigera in northern and
      central Argentina, including the main soybean- and maize-producing area. 

PMID- 26318008
TI  - Sublethal Exposure to Clove and Cinnamon Essential Oils Induces Hormetic-Like
      Responses and Disturbs Behavioral and Respiratory Responses in Sitophilus zeamais
      (Coleoptera: Curculionidae).
AB  - Essential oils have been suggested as suitable alternatives for controlling
      insect pests. However, the potential adaptive responses elicited in insects for
      mitigating the actions of these compounds have not received adequate attention.
      Furthermore, as is widely reported with traditional insecticides, sublethal
      exposure to essential oils might induce stimulatory responses or contribute to
      the development of resistance strategies that can compromise the management of
      insect pests. The current study evaluated the locomotory and respiratory
      responses as well as the number of larvae per grain produced by the maize weevil,
      Sitophilus zeamais Motschulsky, after being sublethally exposed to the essential
      oils of clove, Syzygium aromaticum L., and cinnamon, Cinnamomum zeylanicum L. The
      essential oils showed similar insecticidal toxicity (exposure route: contact with
      dried residues; Clove LC95 = 3.96 [2.78-6.75] ul/cm(2); Cinnamon LC95 = 3.47
      [2.75-4.73] ul/cm(2)). A stimulatory effect on the median survival time (TL50)
      was observed when insects were exposed to low concentrations of each oil.
      Moreover, a higher number of larvae per grain was produced under sublethal
      exposure to clove essential oil. S. zeamais avoided the treated areas (in free
      choice experiments) and altered their mobility when sublethally exposed to both
      essential oils. The respiratory rates of S. zeamais (i.e., CO2 production) were
      significantly reduced under low concentrations of the essential oils. We
      recommend the consideration of the potential sublethal effects elicited by
      botanical pesticides during the development of integrated pest management
      programs aiming to control S. zeamais. 

PMID- 26318009
TI  - Should asymptomatic patients discharged with lower hemoglobin expect worse
      outcomes after valve surgery?
AB  - OBJECTIVE: Blood transfusion in cardiac surgery patients is associated with
      increased morbidity and cost. The decision to transfuse patients after surgery
      varies but is often based on low hemoglobin (Hgb) levels, regardless of symptom
      status. This study examined whether asymptomatic patients discharged with lower
      Hgb levels had increased risk for perioperative complications and 1-year
      mortality. METHODS: Between 2008 and mid-2014, a total of 1107 valve-only
      procedures were performed. Patients discharged alive with complete data (N =
      1044) were divided into 2 groups with discharge Hgb levels of <=8 g/dL (n = 153)
      or >8 g/dL (n = 891). Propensity score matching was conducted between Hgb groups,
      resulting in 152 patient pairs. RESULTS: In multivariate analyses, discharge Hgb
      level did not predict 30-day mortality (odds ratio [OR] = 1.01, P = .991), 1-year
      survival (hazard ratio [HR] = 0.87, P = .34), or readmission <30 days (OR = 0.92,
      P = .31). Furthermore, after propensity score matching, no differences were found
      between groups with Hgb levels <=8 versus >8 g/dL in 30-day mortality (0% vs
      0.7%, P > .99) or readmissions (14% vs 16%, P = .52). Cumulative 1-year survival
      was similar between matched groups with discharge Hgb level of <=8 versus >8 g/dL
      (89.3% vs 91.4%, P = .67). Matched groups with Hgb level <=8 versus >8 g/dL had
      similar physical (28% vs 18% increase; P = .27) and mental (7% vs 6% increase; P
      = .94) health-related quality of life (HRQL) improvements at 6 months.
      CONCLUSIONS: Asymptomatic patients discharged with lower Hgb levels did not
      manifest inferior outcomes, including perioperative morbidity/mortality,
      readmission <30 days, HRQL, and 1-year survival. The practice of blood
      transfusion to correct lower Hgb levels in asymptomatic patients should be
      eliminated, as it may be associated with increased morbidity without apparent
      clinical benefits after valve surgery.

PMID- 26318010
TI  - Long-term survival after use of internal thoracic artery in octogenarians is
      gender related.
AB  - OBJECTIVE: The goal of this study is to assess the benefits of a left internal
      thoracic artery as a bypass conduit in octogenarians undergoing elective coronary
      artery bypass grafting. We hypothesize that there is no survival advantage and
      that outcome may be gender related. METHODS: In a retrospective analysis of 1141
      octogenarians (aged >80 years) undergoing isolated coronary artery bypass
      grafting from 1996 to 2012, patients were divided into 2 groups: Group I
      (coronary artery bypass grafting-left internal thoracic artery) included 870
      patients (339 female/531 male), and group II (coronary artery bypass grafting
      saphenous vein graft) included 271 patients (131 female/140 male). RESULTS: The
      overall 30-day mortality was 5.7%: 4.3% in group I and 7.0% in group II (P = .1).
      Group II had a lower trend of any postoperative complication (P = .05) and
      pneumonia (P = .05). When analyzed by gender, there were no discernable
      differences in long-term survival for male patients in group I (65% at 5 years
      and 29% at 10 years) versus male patients in group II (65% at 5 years and 31% at
      10 years) (P = .2). However, survival was significantly greater for female
      patients in group I (70% at 5 years and 35% at 10 years) versus female patients
      in group II (63% at 5 years and 21% at 19 years) (P = .01). Multiple logistic and
      Cox regression analysis showed that left internal thoracic artery use is
      associated with improved survival in female patients (hazard ratio [HR], 0.72;
      confidence interval [CI], 0.56-0.93) but not in male patients (HR, 1.14; CI, 0.9
      1.4). Advanced age was associated with an increased risk of mortality (HR, 1.08
      per year; CI, 1.05-1.1). Both patient age (P = .01) and Society of Thoracic
      Surgeons-predicted 30-day mortality (P = .03) remain in the final model for 30
      day mortality. The benefit of the left internal thoracic artery after coronary
      artery bypass grafting in octogenarians may be gender related. CONCLUSIONS: This
      study shows that the benefit of the left internal thoracic artery in the
      octogenarian population undergoing coronary artery bypass grafting may be gender
      related. For elderly female patients, the use of the left internal thoracic
      artery as a bypass conduit was associated with better long-term survival, whereas
      no significant difference was found among the male population. The use of the
      left internal thoracic artery was associated with a greater postoperative
      pulmonary morbidity for the study population as a whole. The present study does
      not refute the benefit of the left internal thoracic artery-left anterior
      descending graft, but instead distinguishes a subset who might benefit more.

PMID- 26318011
TI  - Discussion.

PMID- 26318013
TI  - Nothing worth having comes easy.

PMID- 26318012
TI  - Gamification in thoracic surgical education: Using competition to fuel
      performance.
AB  - OBJECTIVES: In an effort to stimulate residents and trainers to increase their
      use of simulation training and the Thoracic Surgery Curriculum, a gamification
      strategy was developed in a friendly but competitive environment. METHODS: "Top
      Gun." Low-fidelity simulators distributed annually were used for the technical
      competition. Baseline and final video assessments were performed, and 5 finalists
      were invited to compete in a live setting from 2013 to 2015. "Jeopardy." A
      screening examination was devised to test knowledge contained in the Thoracic
      Surgery Curriculum. The top 6 2-member teams were invited to compete in a live
      setting structured around the popular game show Jeopardy. RESULTS: "Top Gun."
      Over 3 years, there were 43 baseline and 34 final submissions. In all areas of
      assessment, there was demonstrable improvement. There was increasing evidence of
      simulation as seen by practice and ritualistic behavior. "Jeopardy." Sixty-eight
      individuals completed the screening examination, and 30 teams were formed. The
      largest representation came from the second-year residents in traditional
      programs. Contestants reported an average in-training examination percentile of
      72.9. Finalists reported increased use of the Thoracic Surgery Curriculum by an
      average of 10 hours per week in preparation. The live competition was friendly,
      engaging, and spirited. CONCLUSIONS: This gamification approach focused on
      technical and cognitive skills, has been successfully implemented, and has
      encouraged the use of simulators and the Thoracic Surgery Curriculum. This
      framework may capitalize on the competitive nature of our trainees and can
      provide recognition of their achievements.

PMID- 26318014
TI  - Hippo pathway/Yap regulates primary enamel knot and dental cusp patterning in
      tooth morphogenesis.
AB  - The shape of an individual tooth crown is primarily determined by the number and
      arrangement of its cusps, i.e., cusp patterning. Enamel knots that appear in the
      enamel organ during tooth morphogenesis have been suggested to play important
      roles in cusp patterning. Animal model studies have shown that the Hippo pathway
      effector Yap has a critical function in tooth morphogenesis. However, the role of
      the Hippo pathway/Yap in cusp patterning has not been well documented and its
      specific roles in tooth morphogenesis remain unclear. Here, we provide evidence
      that Yap is a key mediator in tooth cusp patterning. We demonstrate a correlation
      between Yap localization and cell proliferation in developing tooth germs. We
      also show that, between the cap stage and bell stage, Yap is crucial for the
      suppression of the primary enamel knot and for the patterning of secondary enamel
      knots, which are the future cusp regions. When Yap expression is stage
      specifically knocked down during the cap stage, the activity of the primary
      enamel knot persists into the bell-stage tooth germ, leading to ectopic cusp
      formation. Our data reveal the importance of the Hippo pathway/Yap in enamel
      knots and in the proper patterning of tooth cusps. 

PMID- 26318015
TI  - Deamidation of N76 in human gammaS-crystallin promotes dimer formation.
AB  - BACKGROUND: Cataract formation is often attributed to the build-up of post
      translational modifications in the crystallin proteins of the eye lens. One such
      modification, the deamidation of N76 in human gammaS-crystallin to D76, is highly
      correlated with age-related cataract (Hooi et al. Invest. Ophthalmol. Vis. Sci.
      53 (2012) 3554-3561). In the current work, this modification has been extensively
      characterised in vitro. METHODS: Biophysical characterisation was performed on
      wild type and N76D gammaS-crystallins using turbidity measurements to monitor
      aggregation, intrinsic fluorescence and circular dichroism spectroscopy to
      determine the folded state and NMR spectroscopy for identifying local changes in
      structure. Protein mass was determined using SEC-MALLS and analytical
      ultracentrifugation methods. RESULTS: Relative to the wild type protein,
      deamidation at N76 in gammaS-crystallin causes an increase in the thermal
      stability and resistance to thermally induced aggregation alongside a decrease in
      stability to denaturants, a propensity to aggregate rapidly once destabilised and
      a tendency to form a dimer. We ascribe the apparent increase in thermal stability
      upon deamidation to the formation of dimer which prevents the unfolding of the
      inherently less stable monomer. CONCLUSIONS: Deamidation causes a decrease in
      stability of gammaS-crystallin but this is offset by an increased tendency for
      dimer formation. GENERAL SIGNIFICANCE: Deamidation at N76 in human gammaS
      crystallin likely has a combinatorial effect with other post-translational
      crystallin modifications to induce age-related cataract. This article is part of
      a Special Issue entitled Crystallin Biochemistry in Health and Disease.

PMID- 26318016
TI  - Mechanism of polymorphism and curvature of HIV capsid assemblies probed by 3D
      simulations with a novel coarse grain model.
AB  - BACKGROUND: During the maturation process, HIV capsid proteins self-assemble into
      polymorphic capsids. The strong polymorphism precludes high resolution structural
      characterization under in vivo conditions. In spite of the determination of
      structural models for various in vitro assemblies of HIV capsid proteins, the
      assembly mechanism is still not well-understood. METHODS: We report 3D
      simulations of HIV capsid proteins by a novel coarse grain model that captures
      the backbone of the rigid segments in the protein accurately. The effects of
      protein dynamics on assembly are emulated by a static ensemble of subunits in
      conformations derived from molecular dynamics simulation. RESULTS: We show that
      HIV capsid proteins robustly assemble into hexameric lattices in a range of
      conditions where trimers of dimeric subunits are the dominant oligomeric
      intermediates. Variations of hexameric lattice curvatures are observed in
      simulations with subunits of variable inter-domain orientations mimicking the
      conformation distribution in solution. Simulations with subunits based on
      pentameric structural models lead to assembly of sharp curved structures
      resembling the tips of authentic HIV capsids, along a distinct pathway populated
      by tetramers and pentamers with the characteristic quasi-equivalency of viral
      capsids. CONCLUSIONS: Our results suggest that the polymorphism assembly is
      triggered by the inter-domain dynamics of HIV capsid proteins in solution. The
      assembly of highly curved structures arises from proteins in conformation with a
      highly specific inter-domain orientation. SIGNIFICANCE: Our work proposes a
      mechanism of HIV capsid assembly based on available structural data, which can be
      readily verified. Our model can be applied to other large biomolecular
      assemblies.

PMID- 26318017
TI  - The etiology of human age-related cataract. Proteins don't last forever.
AB  - BACKGROUND: It is probable that the great majority of human cataract results from
      the spontaneous decomposition of long-lived macromolecules in the human lens.
      Breakdown/reaction of long-lived proteins is of primary importance and recent
      proteomic analysis has enabled the identification of the particular crystallins,
      and their exact sites of amino acid modification. SCOPE OF REVIEW: Analysis of
      proteins from cataractous lenses revealed that there are sites on some structural
      proteins that show a consistently greater degree of deterioration than age
      matched normal lenses. MAJOR CONCLUSIONS: The most abundant posttranslational
      modification of aged lens proteins is racemization. Deamidation, truncation and
      crosslinking, each arising from the spontaneous breakdown of susceptible amino
      acids within proteins, are also present. Fundamental to an understanding of
      nuclear cataract etiology, it is proposed that once a certain degree of
      modification at key sites occurs, that protein-protein interactions are disrupted
      and lens opacification ensues. GENERAL SIGNIFICANCE: Since long-lived proteins
      are now recognized to be present in many other sites of the body, such as the
      brain, the information gleaned from detailed analyses of degraded proteins from
      aged lenses will apply more widely to other age-related human diseases. This
      article is part of a Special Issue entitled Crystallin Biochemistry in Health and
      Disease.

PMID- 26318018
TI  - Hsp70 plays an important role in high-fat diet induced gestational hyperglycemia
      in mice.
AB  - Gestational diabetes mellitus (GDM) has emerged as an epidemic disease during the
      last decade, affecting about 2 to 5% pregnant women. Even among women who have
      gestational hyperglycemia may also be positively related to adverse outcomes as
      GDM. Since heat shock protein (Hsp) 70 has been reported to be associated with
      diabetes and insulin resistance and its expression was reported to be negatively
      regulated by the membrane-permeable Hsp70 inhibitor MAL3-101 while positively
      regulated by the Hsp70 activator BGP-15, we investigated whether Hsp70 played a
      role in a gestational hyperglycemia mouse model. Mice were divided into non
      pregnant and pregnant groups, and each comprised three subgroups: control, high
      fat diet (HFD) + MAL3-101, and HFD + BGP-15. We examined the serum levels of
      triglycerides, total cholesterol, glucose, and insulin, as well as conducted
      thermal detection of brown adipose tissue (BAT). The role of Hsp70 in BAT
      apoptosis was also investigated by terminal deoxynucleotidyl transferase dUTP
      nick end labeling (TUNEL) assay and caspase-3 staining. Higher serum level of
      Hsp70 was associated with increased bodyweight gain after pregnancy in mice fed
      HFD. Circulating Hsp70 was elevated in control pregnant mice compared to control
      non-pregnant mice. BGP-induced serum Hsp70 expression reduced triglycerides,
      total cholesterol, glucose, and insulin levels in the serum. Additionally,
      thermal detection of BAT, TUNEL, and caspase-3 staining revealed relationship
      correlation between Hsp70 and BAT functions. Hsp70 level is associated with
      hyperglycemia during pregnancy. Our results support the role of Hsp70 in
      facilitating BAT activities and protecting BAT cells from apoptosis via caspase-3
      pathway.

PMID- 26318019
TI  - Prognostic value of endocapillary hypercellularity in IgA nephropathy patients
      with no immunosuppression.
AB  - AIM: Interpretation of retrospective clinicopathological studies of IgA
      nephropathy (IgAN) has been confounded by immunosuppression bias. In published
      validation studies of the Oxford Classification of IgAN, an average of 33 % of
      patients received non-randomised steroid and/or cytotoxic therapy. In order to
      determine the true impact of proliferative lesions on the natural history of
      IgAN, analysis of patient cohorts that have received no immunosuppression is
      required. METHODS: We performed a retrospective single centre study of patients
      with IgAN managed without immunosuppressive therapy. Biopsies were scored
      according to the Oxford Classification. The primary outcomes were renal survival
      or a rapid loss of renal function defined as a decline in eGFR of >5 ml/min/year.
      RESULTS: 237 patients with IgAN were identified with a mean follow-up of 82
      months. 200 had biopsies available for review, of which 156 were adequate for
      scoring using the Oxford Classification. 9/156 patients (5.8 %) received some
      immunosuppressive therapy, mostly for unrelated conditions: these were excluded.
      In multivariate COX regression, including histological and clinical data, the
      only independent predictors of time to ESRD were baseline eGFR (HR 0.96 per
      ml/min increase, p = 0.018), baseline proteinuria (HR 1.36 per doubling, p =
      0.004) and endocapillary hypercellularity (HR 4.75 for E1 compared to E0, p <
      0.001). Independent predictors of a rapid decline in eGFR were proteinuria (OR
      1.45 per doubling, p = 0.006), endocapillary hypercellularity (OR 3.41 for E1
      compared to E0, p = 0.025) and tubular atrophy/interstitial fibrosis (OR 8.77 for
      T2 compared to T0, p = 0.006). CONCLUSIONS: In a cohort of IgAN patients
      receiving no immunosuppression, endocapillary proliferation and tubular
      atrophy/interstitial fibrosis are independent predictors of rate of loss of renal
      function. The lack of predictive value of E score in other clinicopathological
      studies is most likely a result of immunosuppression-associated bias. Our
      findings provide evidence to support immunosuppressive treatment of endocapillary
      pattern IgAN.

PMID- 26318020
TI  - Reversible vascular calcifications associated with hypervitaminosis D.
AB  - A 64-year-old man was hospitalized in 2002 with symptoms of stupor, weakness, and
      renal colic. The clinical examination indicated borderline hypertension, small
      masses in the glutei, and polyuria. Laboratory tests evidenced high serum
      concentrations of creatinine, calcium, and phosphate. Imaging assessments
      disclosed widespread vascular calcifications, gluteal calcifications, and pelvic
      ectasia. Subsequent lab tests indicated suppressed serum parathyroid hormone,
      extremely high serum 25-hydroxy vitamin D, and normal serum 1,25-dihydroxy
      vitamin D. Treatment was started with intravenous infusion of saline and
      furosemide due to the evidence of hypercalcemia. Prednisone and omeprazole were
      added given the evidence of hypervitaminosis D. The treatment improved serum
      calcium, kidney function, and consciousness. The medical history disclosed recent
      treatment with exceptionally high doses of slow-release intra-muscular
      cholecalciferol and the recent excretion of urinary stones. The patient was
      discharged when it was possible to stop the intravenous treatment. The post
      discharge treatment included oral hydration, furosemide, prednisone and
      omeprazole for approximately 6 months up to complete resolution of the
      hypercalcemia. The patient came back 12 years later because of microhematuria.
      Lab tests were normal for calcium/phosphorus homeostasis and kidney function.
      Imaging tests indicated only minor vascular calcifications. This is the first
      evidence of reversible vascular calcifications secondary to hypervitaminosis D. 

PMID- 26318022
TI  - The Global Alzheimer's Association Interactive Network.
AB  - INTRODUCTION: The Global Alzheimer's Association Interactive Network (GAAIN) is
      consolidating the efforts of independent Alzheimer's disease data repositories
      around the world with the goals of revealing more insights into the causes of
      Alzheimer's disease, improving treatments, and designing preventative measures
      that delay the onset of physical symptoms. METHODS: We developed a system for
      federating these repositories that is reliant on the tenets that (1) its
      participants require incentives to join, (2) joining the network is not
      disruptive to existing repository systems, and (3) the data ownership rights of
      its members are protected. RESULTS: We are currently in various phases of
      recruitment with over 55 data repositories in North America, Europe, Asia, and
      Australia and can presently query >250,000 subjects using GAAIN's search
      interfaces. DISCUSSION: GAAIN's data sharing philosophy, which guided our
      architectural choices, is conducive to motivating membership in a voluntary data
      sharing network.

PMID- 26318023
TI  - Conservative management of typical pediatric postauricular dermoid cysts.
AB  - OBJECTIVE: Congenital dermoid cysts of the skull and face frequently arise in
      embryonic fusion planes. They may follow these planes to extend intratemporally
      or intracranially. Advanced imaging and operative techniques are generally
      recommended for these lesions. Postauricular temporal bone dermoid cysts seem to
      form a distinct subgroup with a lesser tendency toward deep extension. They may
      be amenable to more conservative management strategies. METHODS: With IRB
      approval, we queried a prospectively-accrued computerized patient-care database
      to find all postauricular temporal dermoid lesions surgically managed by a single
      pediatric otolaryngologist from 2001 to 2014. We reviewed the English-language
      literature to identify similar series of surgically treated pediatric temporal
      bone dermoid cysts. RESULTS: Ten postauricular temporal dermoid cysts with
      pathological confirmation were identified in our surgical series. The average
      size of the lesions was 1.5 cm (0.3-3 cm). The average age at time of surgery was
      4 years (6 months-17 years). No intracranial extension was observed at surgery.
      There were no recurrences noted on last follow-up (mean 65 months, range 10-150
      months). A computerized literature review found no examples of intracranial
      extension among typical postauricular dermoid cysts. CONCLUSION: There was no
      intracranial or temporal extension in our series or among postauricular lesions
      described in the literature. Given the low incidence of deep extension we
      advocate neither advanced imaging nor routine neurosurgical consultation for
      typical postauricular lesions. Dissection in continuity with cranial periosteum
      facilitates intact removal of adherent lesions. Surgery is curative if the
      dermoid is removed intact.

PMID- 26318024
TI  - Paradoxical vocal cord movement during sleep - A unique case with review of
      literature.
AB  - Paradoxical vocal cord movement (PVCM) refers to paradoxical adduction of the
      true vocal cords during inspiration resulting in variable upper airway
      obstruction. The condition often presents with shortness of breath, wheeze or
      stridor, mimicking bronchial asthma. Both organic and non-organic causes have
      been described. PVCM occurring only during sleep has rarely been reported in
      patients with CNS disease. We present a case of PVCM occurring only during sleep
      in a 14-year-old boy without any CNS disease, who was initially misdiagnosed as
      bronchial asthma. 

PMID- 26318021
TI  - Rbpj-kappa mediated Notch signaling plays a critical role in development of
      hypothalamic Kisspeptin neurons.
AB  - The mammalian arcuate nucleus (ARC) houses neurons critical for energy
      homeostasis and sexual maturation. Proopiomelanocortin (POMC) and Neuropeptide Y
      (NPY) neurons function to balance energy intake and Kisspeptin neurons are
      critical for the onset of puberty and reproductive function. While the
      physiological roles of these neurons have been well established, their
      development remains unclear. We have previously shown that Notch signaling plays
      an important role in cell fate within the ARC of mice. Active Notch signaling
      prevented neural progenitors from differentiating into feeding circuit neurons,
      whereas conditional loss of Notch signaling lead to a premature differentiation
      of these neurons. Presently, we hypothesized that Kisspeptin neurons would
      similarly be affected by Notch manipulation. To address this, we utilized mice
      with a conditional deletion of the Notch signaling co-factor Rbpj-kappa (Rbpj
      cKO), or mice persistently expressing the Notch1 intracellular domain (NICD tg)
      within Nkx2.1 expressing cells of the developing hypothalamus. Interestingly, we
      found that in both models, a lack of Kisspeptin neurons are observed. This
      suggests that Notch signaling must be properly titrated for formation of
      Kisspeptin neurons. These results led us to hypothesize that Kisspeptin neurons
      of the ARC may arise from a different lineage of intermediate progenitors than
      NPY neurons and that Notch was responsible for the fate choice between these
      neurons. To determine if Kisspeptin neurons of the ARC differentiate similarly
      through a Pomc intermediate, we utilized a genetic model expressing the tdTomato
      fluorescent protein in all cells that have ever expressed Pomc. We observed some
      Kisspeptin expressing neurons labeled with the Pomc reporter similar to NPY
      neurons, suggesting that these distinct neurons can arise from a common
      progenitor. Finally, we hypothesized that temporal differences leading to
      premature depletion of progenitors in cKO mice lead to our observed phenotype.
      Using a BrdU birthdating paradigm, we determined the percentage of NPY and
      Kisspeptin neurons born on embryonic days 11.5, 12.5, and 13.5. We found no
      difference in the timing of differentiation of either neuronal subtype, with a
      majority occurring at e11.5. Taken together, our findings suggest that active
      Notch signaling is an important molecular switch involved in instructing
      subpopulations of progenitor cells to differentiate into Kisspeptin neurons. 

PMID- 26318025
TI  - Congenital nasal pyriform aperture stenosis 5.7 mm or less is associated with
      surgical intervention: A pooled case series.
AB  - OBJECTIVES: Congenital nasal pyriform aperture stenosis (CNPAS) is a rare cause
      of upper airway obstruction in the newborn. CNPAS is diagnosed clinically and
      confirmed with CT scanning. Early diagnosis and management is essential for this
      potentially life-threatening condition. Patients can be managed conservatively or
      surgically. Surgical treatment is usually reserved for those patients that fail
      conservative treatment. Our objective was to provide a radiologically-measured
      pyriform aperture (PA) width that predicts the need for surgical intervention.
      METHODS: This study was a retrospective chart review of patients treated in a
      tertiary paediatric hospital as well as a review of the literature. Outcome
      measures were defined as surgical or conservative intervention for the management
      of congenital pyriform aperture stenosis. RESULTS: Data from 26 individual
      patients (7 patients from our own case series and 19 patients from previously
      published reports) was analysed to calculate those patients requiring surgical
      intervention. CONCLUSIONS: A PA width of less than 5.7 mm in a neonate is 88%
      sensitive and specific in predicting that a patient will require surgical
      intervention.

PMID- 26318026
TI  - Impact of anal decompression on anastomotic leakage after low anterior resection
      for rectal cancer: a propensity score matching analysis.
AB  - PURPOSE: The effectiveness of a transanal drainage tube for the prevention of
      anastomotic leakage (AL) is still uncertain. This study aimed to investigate the
      impact of anal decompression on AL after rectal cancer surgery. METHODS: We
      retrospectively reviewed 536 rectal cancer patients who underwent low anterior
      resection without diverting stoma, with (n = 154) or without (n = 382) placing of
      a transanal drainage tube, between January 2005 and December 2014. Risk factors
      for AL were analyzed, and propensity score matching analysis was used to
      compensate for the differences in baseline characteristics. RESULTS: AL occurred
      in 50 (9.3%) of the patients. Male sex (odds ratio [OR] 3.097, p = 0.005), high
      ASA score (OR 3.505, p = 0.025), and neoadjuvant chemoradiation (OR 2.506, p =
      0.018) were independent predictors of AL on multivariable analysis. After
      propensity score matching, transanal drainage tube tended to lessen rates of
      grade C AL with definite peritonitis (1.9 vs. 5.8%, p = 0.077), although there
      was no difference in the incidence of AL in patients with or without transanal
      drainage tubes (5.8 vs. 9.1%, p = 0.278). CONCLUSIONS: Placement of a transanal
      drainage tube was not associated with a reduction in the total incidence of AL
      after low anterior resection for rectal cancer.

PMID- 26318027
TI  - Genome neighborhood network reveals insights into enediyne biosynthesis and
      facilitates prediction and prioritization for discovery.
AB  - The enediynes are one of the most fascinating families of bacterial natural
      products given their unprecedented molecular architecture and extraordinary
      cytotoxicity. Enediynes are rare with only 11 structurally characterized members
      and four additional members isolated in their cycloaromatized form. Recent
      advances in DNA sequencing have resulted in an explosion of microbial genomes. A
      virtual survey of the GenBank and JGI genome databases revealed 87 enediyne
      biosynthetic gene clusters from 78 bacteria strains, implying that enediynes are
      more common than previously thought. Here we report the construction and analysis
      of an enediyne genome neighborhood network (GNN) as a high-throughput approach to
      analyze secondary metabolite gene clusters. Analysis of the enediyne GNN
      facilitated rapid gene cluster annotation, revealed genetic trends in enediyne
      biosynthetic gene clusters resulting in a simple prediction scheme to determine 9
      versus 10-membered enediyne gene clusters, and supported a genomic-based strain
      prioritization method for enediyne discovery. 

PMID- 26318028
TI  - Fatty alcohols production by oleaginous yeast.
AB  - We have engineered Rhodosporidium toruloides to produce fatty alcohols by
      expressing a fatty acyl-CoA reductase from Marinobacter aquaeolei VT8. Production
      of fatty alcohols in flasks was achieved in different fermentation media at
      titers ranging from 0.2 to 2 g/L. In many of the conditions tested, more than 80
      % of fatty alcohols were secreted into the cultivation broth. Through fed-batch
      fermentation in 7 L bioreactors, over 8 g/L of C(16)-C(18) fatty alcohols were
      produced using sucrose as the substrate. This is the highest titer ever reported
      on microbial production of fatty alcohols to date.

PMID- 26318029
TI  - Expression and display of a novel thermostable esterase from Clostridium
      thermocellum on the surface of Bacillus subtilis using the CotB anchor protein.
AB  - Esterases expressed in microbial hosts are commercially valuable, but their
      applications are limited due to high costs of production and harsh industrial
      processes involved. In this study, the esterase-DSM (from Clostridium
      thermocellum) was expressed and successfully displayed on the spore surface, and
      the spore-associated esterase was confirmed by western blot analysis and activity
      measurements. The optimal temperature and pH of spore surface-displayed DSM was
      60 and 8.5  degrees C, respectively. It also demonstrates a broad temperature and
      pH optimum in the range of 50-70, 7-9.5  degrees C. The spore surface-displayed
      esterase-DSM retained 78, 68 % of its original activity after 5 h incubation at
      60 and 70  degrees C, respectively, which was twofold greater activity than that
      of the purified DSM. The recombinant spores has high activity and stability in
      DMSO, which was 49 % higher than the retained activity of the purified DSM in
      DMSO (20 % v/v), and retained 65.2 % of activity after 7 h of incubation in DMSO
      (20 % v/v). However, the recombinant spores could retain 77 % activity after 3
      rounds of recycling. These results suggest that enzyme displayed on the surface
      of the Bacillus subtilis spore could serve as an effective approach for enzyme
      immobilization.

PMID- 26318031
TI  - Surface functionalization of microgrooved titanium with dual growth factor
      releasing nanoparticles for synergistic osteogenic differentiation of human
      mesenchymal stem cells.
AB  - We demonstrate that dual release of bone morphogenic protein-2 (BMP-2) and
      insulin-like growth factor-1 (IGF-1) by catechol-functionalized adhesive polymer
      nanoparticles on microgrooved titanium (Ti) surface enhances in vitro
      osteoblastic differentiation of human mesenchymal stem cells (MSCs). The
      nanoparticles consisted of three distinct domains, surface Ti-adhesive catechol
      groups, anionic poly(L-aspartic acid) (PAsp) shells, and hydrophobic poly(L
      phenylalanine) (PPhe) cores. The immobilization of the adhesive nanoparticles
      onto microgrooved Ti surface was verified using various surface analytical tools,
      such as field-emission scanning electron microscopy (Fe-SEM), X-ray photoelectron
      spectroscopy (XPS), contact angle measurement. The nanoparticles were immobilized
      both on the groove bottom surface and the ridge top surface with a similar
      anchoring density. A fluorescence microscope visualized that BMP-2 and IGF-1 of
      positive charges were efficiently loaded onto the negatively charged PAsp shells
      of immobilized nanoparticles. We confirmed the enhanced osteoblastic
      differentiation of MSCs by presenting the expression results of major osteoblast
      marker genes and proteins. In addition, overall significant correlations between
      the experimental results verified the validity of our study. The proposed
      combined surface of microgrooves and growth factor-releasing nanoparticles can be
      used as a strong osteogenic promoter on various biomaterial surfaces. 

PMID- 26318032
TI  - HPLC-FLD and spectrofluorometer apparatus: How to best detect fluorescent probe
      loaded niosomes in biological samples.
AB  - The analytical tools allow the detection of bioactive compounds, diagnostic
      agents and chemotherapeutics. Recently, new methods have been developed to
      analyze pharmaceutical samples and ingredients. In this attempt, analytical
      parameters, e.g., the lack of trueness, robustness and sensitivity, play a
      pivotal role to quantify and analyze molecules, both for diagnostic applications
      as well as therapeutic treatments. Spectrophotometers and spectrofluorometers are
      apparatus for easy and rapid quantification of molecular probes and
      chemotherapeutics into cells, plasma and tissues. However, they lack accuracy and
      precision. Conversely, HPLC provides the maximum resolution to detect and
      separate fluorescent probes and chemotherapeutics after their incubation in
      cells, plasma and tissues. The aim of this work was to develop an HPLC method
      that easily detects molecular and fluorescent probes, e.g., Nile Red, in
      biological samples. To improve the robustness of the method, Nile Red was
      analyzed before and after loading into niosomes made from Tween 20 and 21,
      respectively. A significant difference was further obtained by comparing the
      entrapment efficacy percentage of niosomes made from Tween 21 (42.23%) and Tween
      20 (53.25%). The comparison between HPLC and spectrofluorometer assays showed
      differences between the two methods in terms of limit of detection, linearity and
      accuracy. The resulting data demonstrated that the HPLC-FLD provides a limit of
      detection for Nile Red of 0.1 ng/mL, and a good linearity up to 62.5 ng/mL. The
      HPLC-FLD analysis showed a limit of quantification value for a total mass of Nile
      Red 1200-folds better than data previously reported in studies; and 312-folds
      better than the spectrofluorometer analysis. Additionally, results show that the
      HPLC-FLD increases the sensitivity for biological samples compared to the
      spectrofluorometer. The Nile Red-loaded niosomes were also incubated at different
      times with HEK-293 cells. In vitro results demonstrated that the HPLC-FLD
      apparatus detects Nile Red-loaded niosomes at higher concentrations into HEK-293
      cells than the spectrofluorometer. The intracellular uptake of Nile Red was
      increased at 120 and 24 min using niosomes made from Tween 20 and 21,
      respectively, and its intracellular accumulation shows a time-dependent
      internalization over 120 min of incubation time.

PMID- 26318030
TI  - Prediction of Late Death or Disability at Age 5 Years Using a Count of 3 Neonatal
      Morbidities in Very Low Birth Weight Infants.
AB  - OBJECTIVE: To evaluate bronchopulmonary dysplasia (BPD), serious brain injury,
      and severe retinopathy of prematurity (ROP) as predictors of poor long-term
      outcome in very low birth weight infants. STUDY DESIGN: We examined the
      associations between counts of the 3 morbidities and long-term outcomes in 1514
      of 1791 (85%) infants with birth weights of 500-1250 g who were enrolled in the
      Caffeine for Apnea of Prematurity trial from October 1999, to October 2004, had
      complete morbidity data, and were alive at 36 weeks postmenstrual age (PMA). BPD
      was defined as use of supplemental oxygen at 36 weeks PMA. Serious brain injury
      on cranial ultrasound included grade 3 and 4 hemorrhage, cystic periventricular
      leucomalacia, porencephalic cysts, or ventriculomegaly of any cause. Poor long
      term outcome was death after 36 weeks PMA or survival to 5 years with 1 or more
      of the following disabilities: motor impairment, cognitive impairment, behavior
      problems, poor general health, deafness, and blindness. RESULTS: BPD, serious
      brain injury, and severe ROP occurred in 43%, 13%, and 6% of the infants,
      respectively. Each of the 3 morbidities was similarly and independently
      correlated with poor 5-year outcome. Rates of death or disability (95% CI) in
      children with none, any 1, any 2, and all 3 morbidities were 11.2% (9.0%-13.7%),
      22.9% (19.6%-26.5%), 43.9% (35.5%-52.6%), and 61.5% (40.6%-79.8%), respectively.
      CONCLUSIONS: In very low birth weight infants who survive to 36 weeks PMA, a
      count of BPD, serious brain injury, and severe ROP predicts the risk of a late
      death or survival with disability at 5 years.

PMID- 26318033
TI  - AKT3 promotes prostate cancer proliferation cells through regulation of Akt, B
      Raf, and TSC1/TSC2.
AB  - The qRT-PCR analysis of 139 clinical samples and analysis of 150 on-line database
      clinical samples indicated that AKT3 mRNA expression level was elevated in
      primary prostate tumors. Immunohistochemical staining of 65 clinical samples
      revealed that AKT3 protein expression was higher in prostate tumors of stage I,
      II, III as compared to nearby normal tissues. Plasmid overexpression of AKT3
      promoted cell proliferation of LNCaP, PC-3, DU-145, and CA-HPV-10 human prostate
      cancer (PCa) cells, while knockdown of AKT3 by siRNA reduced cell proliferation.
      Overexpression of AKT3 increased the protein expression of total AKT, phospho-AKT
      S473, phospho-AKT T308, B-Raf, c-Myc, Skp2, cyclin E, GSK3beta, phospho-GSK3beta
      S9, phospho-mTOR S2448, and phospho-p70S6K T421/S424, but decreased TSC1
      (tuberous sclerosis 1) and TSC2 (tuberous Sclerosis Complex 2) proteins in PC-3
      PCa cells. Overexpression of AKT3 also increased protein abundance of phospho-AKT
      S473, phospho-AKT T308, and B-Raf but decreased expression of TSC1 and TSC2
      proteins in LNCaP, DU-145, and CA-HPV-10 PCa cells. Oncomine datasets analysis
      suggested that AKT3 mRNA level was positively correlated to BRAF. Knockdown of
      AKT3 in DU-145 cells with siRNA increased the sensitivity of DU-145 cells to B
      Raf inhibitor treatment. Knockdown of TSC1 or TSC2 promoted the proliferation of
      PCa cells. Our observations implied that AKT3 may be a potential therapeutic
      target for PCa treatment. 

PMID- 26318034
TI  - Nef-M1, a peptide antagonist of CXCR4, inhibits tumor angiogenesis and epithelial
      to-mesenchymal transition in colon and breast cancers.
AB  - The Nef-M1 peptide competes effectively with the natural ligand of CXC chemokine
      receptor 4 (CXCR4), stromal cell-derived factor 1-alpha, to induce apoptosis and
      inhibit growth in colon cancer (CRC) and breast cancer (BC). Its role in tumor
      angiogenesis, and epithelial-to-mesenchymal transition (EMT) regulation, key
      steps involved in tumor growth and metastasis, are unknown. We evaluated the
      angioinhibitory effect of Nef-M1 peptide and examined its role in the inhibition
      of EMT in these cancers. Colon (HT29) and breast (MDA-MB231) cancer cells
      expressing CXCR4 were studied in vitro and in xenograft tumors propagated in
      severe combined immunodeficient mice. The mice were treated intraperitoneally
      with Nef-M1 or scrambled amino acid sequence of Nef-M1 (sNef-M1) peptide, a
      negative control, starting at the time of tumor implantation. Sections from
      tumors were evaluated for tumor angiogenesis, as measured by microvessel density
      (MVD) based on immunostaining of endothelial markers. In vitro tumor angiogenesis
      was assessed by treating human umbilical vein endothelial cells with conditioned
      media from the tumor cell lines. A BC cell line (MDA-MB 468) which does not
      express CXCR4 was used to study the actions of Nef-M1 peptide. Western blot and
      immunofluorescence analyses assessed the effect of Nef-M1 on tumor angiogenesis
      and EMT in both tumors and cancer cells. Metastatic lesions of CRC and BC
      expressed more CXCR4 than primary lesions. It was also found that tumors from
      mice treated with sNef-M1 had well established vascularity, while Nef-M1 treated
      tumors had very poor vascularization. Indeed, the mean MVD was lower in tumors
      from Nef-M1 treated mice than in sNef-M1 treated tumors. Nef-M1 treated tumor has
      poor morphology and loss of endothelial integrity. Although conditioned medium
      from CRC or BC cells supported HUVEC tube formation, the conditioned medium from
      Nef-M1 treated CRC or BC cells did not support tube formation. Western blot
      analyses revealed that Nef-M1 effectively suppressed the expression of VEGF-A in
      CRC and BC cells and tumors. This suggests that Nef-M1 treated CRC and BC cells
      are more consistent with E-cadherin signature, and thus appears more epithelial
      in nature. Our data indicate that Nef-M1 peptide inhibits tumor angiogenesis and
      the oncogenic EMT process. Targeting the chemokine receptor, CXCR4, mediated
      pathways using Nef-M1 may prove to be a novel therapeutic approach for CRC and
      BC. 

PMID- 26318035
TI  - SIRT1 in B[a]P-induced lung tumorigenesis.
AB  - Benzo[a]pyrene (B[a]P) is a carcinogen in cigarette smoke. We found that B[a]P
      induced SIRT1 in human bronchial epithelial BEAS-2B cell. SIRT1 was overexpressed
      in the lung of B[a]P-exposed mice and in human lung cancer biopsies. SIRT1 up
      regulated TNF-alpha and beta-catenin and down-regulated the membrane fraction of
      E-cadherin. In addition, SIRT1 promoted invasion, migration and tumorigenesis of
      BEAS-2B cells in nude mice upon B[a]P exposure. Thus, SIRT1 is involved in B[a]P
      induced transformation associated with activation of the TNF-alpha/beta-catenin
      axis and is as a potential therapeutic target for lung cancer. 

PMID- 26318037
TI  - The prognosis was poorer in colorectal cancers that expressed both VEGF and PROK1
      (No correlation coefficient between VEGF and PROK1).
AB  - The angiogenic proteins vascular endothelial growth factor (VEGF) and
      prokineticin1 (PROK1) proteins are considered important in colorectal cancer, the
      relationship between their simultaneous expression and prognosis was investigated
      in the present study. VEGF and PROK1 expression in 620 primary human colorectal
      cancer lesions was confirmed via immunohistochemical staining with anti-VEGF and
      anti-PROK1 antibodies, and the correlation between the expression of these 2
      proteins and recurrence/prognosis were investigated. VEGF protein was expressed
      in 329 (53.1%) and PROK1 protein was expressed in 223 (36.0%). PROK1 and VEGF
      were simultaneously expressed in 116 (18.7%) of the 620 cases. The correlation
      coefficient between VEGF expression and PROK1 expression was r = 0.11, and
      therefore correlation was not observed. Clinical pathology revealed that
      substantially lymphnode matastasis, hematogenous metastasis, or TMN advanced
      stage IV was significantly more prevalent in cases that expressed both VEGF and
      PROK1 than in the cases negative for both proteins or those positive for only 1
      of the proteins. Also the cases positive for both proteins exhibited the worst
      recurrence and prognosis. In the Cox proportional hazards model, VEGF and PROK1
      expression was an independent prognostic factor. The prognosis was poorer in
      colorectal cancers that expressed both PROK1 and VEGF relative to the cases that
      expressed only 1 protein, and the expression of both proteins was found to be an
      independent prognostic factor.

PMID- 26318036
TI  - COP9 signalosome subunit 6 (CSN6) regulates E6AP/UBE3A in cervical cancer.
AB  - Cervical cancer is one of the leading causes of cancer death in women. Human
      papillomaviruses (HPVs) are the major cause in almost 99.7% of cervical cancer.
      E6 oncoprotein of HPV and E6-associated protein (E6AP) are critical in causing
      p53 degradation and malignancy. Understanding the E6AP regulation is critical to
      develop treating strategy for cervical cancer patients. The COP9 signalosome
      subunit 6 (CSN6) is involved in ubiquitin-mediated protein degradation. We found
      that both CSN6 and E6AP are overexpressed in cervical cancer. We characterized
      that CSN6 associated with E6AP and stabilized E6AP expression by reducing E6AP
      poly-ubiquitination, thereby regulating p53 activity in cell proliferation and
      apoptosis. Mechanistic studies revealed that CSN6-E6AP axis can be regulated by
      EGF/Akt signaling. Furthermore, inhibition of CSN6-E6AP axis hinders cervical
      cancer growth in mice. Taken together, our results indicate that CSN6 is a
      positive regulator of E6AP and is important for cervical cancer development. 

PMID- 26318039
TI  - Nanoparticle-induced intraperitoneal hyperthermia and targeted photoablation in
      treating ovarian cancer.
AB  - Hyperthermic intraperitoneal chemotherapy is effective in treating various intra
      abdominal malignancies. However, this therapeutic modality can only be performed
      during surgical operations and cannot be used repeatedly. We propose repeatedly
      noninvasive hyperthermia mediated by pegylated silica-core gold nanoshells
      (pSGNs) in vivo with external near-infrared (NIR) laser irradiation. This study
      demonstrated that repeated photothermal treatment can effectively eliminate
      intraperitoneal tumors in mouse ovarian cancer models without damage of normal
      tissues. By conjugating pSGNs with anti-human CD47 monoclonal antibody, a
      significant photoablative effect can be achieved using lower amount of pSGNs and
      shorter NIR laser irradiation. Conjugated pSGNs specifically targeted and bound
      to cancer cells inside the peritoneal cavity. Our results indicate the
      possibility of a noninvasive method of repeated hyperthermia and photoablative
      therapies using nanoparticles. This has substantial clinical potential in
      treating ovarian and other intraperitoneal cancers. 

PMID- 26318040
TI  - PD-1: Dual guard for immunopathology.

PMID- 26318038
TI  - Nuclear estrogen receptor-alpha expression is an independent predictor of
      recurrence in male patients with pT1aN0 lung adenocarcinomas, and correlates with
      regulatory T-cell infiltration.
AB  - BACKGROUND: Tumor biology of estrogen receptor-alpha (ERalpha) and progesterone
      receptor (PR) has been studied in breast cancers. However, clinical impact in
      lung cancer remains controversial. In our study, we investigate whether ERalpha
      and PR expression predicts disease recurrence and correlates with immunologic
      factors in stage I lung adenocarcinoma. METHODS: We reviewed patients with
      pathologic stage I resected lung adenocarcinoma. Tumors were classified according
      to the IASLC/ATS/ERS classification. Immunostaining of ERalpha and PR was
      performed using tissue microarrays (n = 913). Immunostaining of CD3+ and forkhead
      box P3 (FoxP3)+ lymphocyte infiltration, interleukin-7 receptor (IL-7R), and IL
      12Rbeta2 were performed. Cumulative incidence of recurrence (CIR) analysis was
      used to estimate probability of recurrence. RESULTS: Nuclear ERalpha expression
      was observed in 157 (17%) patients and presented more frequently in females (P =
      0.038) and smaller tumors (P = 0.019). Nuclear ERalpha expression was not
      identified in mucinous tumors. In pT1a patients, 5-year CIR of patients with
      ERalpha-positive tumors was significantly higher (5-year CIR, 20%) than those
      with ERalpha-negative tumors (8%; P = 0.018). This difference was statistically
      significant in males (P = 0.003) but not females (P = 0.55). On multivariate
      analysis, nuclear ERalpha expression was an independent predictor of recurrence
      (hazard ratio = 2.27; P = 0.030). In pT1a patients, nuclear ERalpha expression
      positively correlated with tumoral FoxP3+ lymphocytes (P < 0.001), FoxP3/CD3
      index (P < 0.001), and IL-7R (P = 0.022). CONCLUSIONS: Nuclear ERalpha expression
      is an independent predictor of recurrence in pT1a lung adenocarcinomas and
      correlates with poor prognostic immune microenvironments.

PMID- 26318041
TI  - Complementing regeneration.

PMID- 26318042
TI  - TCR signals fuel Treg cells.

PMID- 26318043
TI  - TPL2 mediates IL-17R signaling in neuroinflammation.

PMID- 26318044
TI  - Trypsinogen 4 boosts tumor endothelial cells migration through proteolysis of
      tissue factor pathway inhibitor-2.
AB  - Proteases contribute to cancer in many ways, including tumor vascularization and
      metastasis, and their pharmacological inhibition is a potential anticancer
      strategy. We report that human endothelial cells (EC) express the trypsinogen 4
      isoform of the serine protease 3 (PRSS3), and lack both PRSS2 and PRSS1.
      Trypsinogen 4 expression was upregulated by the combined action of VEGF-A, FGF-2
      and EGF, angiogenic factors representative of the tumor microenvironment.
      Suppression of trypsinogen 4 expression by siRNA inhibited the angiogenic milieu
      induced migration of EC from cancer specimens (tumor-EC), but did not affect EC
      from normal tissues. We identified tissue factor pathway inhibitor-2 (TFPI-2), a
      matrix associated inhibitor of cell motility, as the functional target of
      trypsinogen 4, which cleaved TFPI-2 and removed it from the matrix put down by
      tumor-EC. Silencing tumor-EC for trypsinogen 4 accumulated TFPI2 in the matrix.
      Showing that angiogenic factors stimulate trypsinogen 4 expression, which
      hydrolyses TFPI-2 favoring a pro-migratory situation, our study suggests a new
      pathway linking tumor microenvironment signals to endothelial cell migration,
      which is essential for angiogenesis and blood vessel remodeling. Abolishing
      trypsinogen 4 functions might be an exploitable strategy as anticancer,
      particularly anti-vascular, therapy. 

PMID- 26318045
TI  - Addiction of pancreatic cancer cells to zinc-finger transcription factor ZIC2.
AB  - Activity of GLI transcription factors of Hedgehog signaling is key for various
      cancer cell properties, especially in pancreatic ductal adenocarcinoma (PDAC).
      Zinc-finger transcriptional regulators ZIC1 to ZIC5 of ZIC gene family were
      demonstrated to associate with GLI to increase the nuclear accumulation and
      transcriptional activity of GLI. Notwithstanding this supportive role for GLI
      dependent transcription, it was not fully understood whether ZIC plays an
      independent role in cancer cell biology. Here, we found that ZIC2 is
      indispensable in the regulation of PDAC cell apoptosis. We found that human PDAC
      cell lines uniquely express ZIC2. ZIC2 knockdown induced PDAC cell apoptosis;
      conversely, ZIC2 over-expression enhanced the cellular proliferation. Through a
      comprehensive screening, we identified fibroblast growth factor receptor 3
      (FGFR3) and ANNEXIN A8 (ANXA8) as genes up-regulated by ZIC2 in PDAC cells. The
      forced expression of these two genes cooperatively rescued the apoptosis of ZIC2
      knockdown cells. Immunohistochemical analyses further supported the correlation
      of ZIC2 expression and these genes in human pancreata harboring PDAC.
      Intriguingly, the ZIC2-mediated up-regulation of FGFR3 and ANXA8 was indicated to
      be GLI -independent. This evidence highlights the indispensable role of ZIC2 in
      regulating cellular proliferation and apoptosis during PDAC development and
      suggests a potential therapeutic target for PDAC. 

PMID- 26318046
TI  - Inhibition of adipose triglyceride lipase (ATGL) by the putative tumor suppressor
      G0S2 or a small molecule inhibitor attenuates the growth of cancer cells.
AB  - The G0/G1 switch gene 2 (G0S2) is methylated and silenced in a wide range of
      human cancers. The protein encoded by G0S2 is an endogenous inhibitor of lipid
      catabolism that directly binds adipose triglyceride lipase (ATGL). ATGL is the
      rate-limiting step in triglyceride metabolism. Although the G0S2 gene is silenced
      in cancer, the impact of ATGL in the growth and survival of cancer cells has
      never been addressed. Here we show that ectopic expression of G0S2 in non-small
      cell lung carcinomas (NSCL) inhibits triglyceride catabolism and results in lower
      cell growth. Similarly, knockdown of ATGL increased triglyceride levels,
      attenuated cell growth and promoted apoptosis. Conversely, knockdown of
      endogenous G0S2 enhanced the growth and invasiveness of cancer cells. G0S2 is
      strongly induced in acute promyelocytic leukemia (APL) cells in response to all
      trans retinoic acid (ATRA) and we show that inhibition of ATGL in these cells by
      G0S2 is required for efficacy of ATRA treatment. Our data uncover a novel tumor
      suppressor mechanism by which G0S2 directly inhibits activity of a key
      intracellular lipase. Our results suggest that elevated ATGL activity may be a
      general property of many cancer types and potentially represents a novel target
      for chemotherapy. 

PMID- 26318047
TI  - Structural identification of putative USPs in Catharanthus roseus.
AB  - Nucleotide sequences of the C. roseus SRA database were assembled and translated
      in order to detect putative universal stress proteins (USPs). Based on the known
      conserved USPA domain, 24 Pfam putative USPA proteins in C. roseus were detected
      and arranged in six architectures. The USPA-like domain was detected in all
      architectures, while the protein kinase-like (or PK-like), (tyr)PK-like and/or U
      box domains are shown downstream it. Three other domains were also shown to
      coexist with the USPA domain in C. roseus putative USPA sequences. These domains
      are tetratricopeptide repeat (or TPR), apolipophorin III (or apoLp-III) and Hsp90
      co-chaperone Cdc37. Subsequent analysis divided USPA-like domains based on the
      ability to bind ATP. The multiple sequence alignment indicated the occurrence of
      eight C. roseus residues of known features of the bacterial 1MJH secondary
      structure. The data of the phylogenetic tree indicated several distinct groups of
      USPA-like domains confirming the presence of high level of sequence conservation
      between the plant and bacterial USPA-like sequences. 

PMID- 26318048
TI  - Multiplex SSR-PCR approaches for semi-automated genotyping and characterization
      of loci linked to blast disease resistance genes in rice.
AB  - In the present study, 63 polymorphic microsatellite markers related to rice blast
      resistance genes were fluorescently labelled at the 5'-end with either 6-FAM or
      HEX using the G5 dye set and incorporated into a multiplex SSR-PCR for the
      detection of fragments using an automated system. For rice F3 families obtained
      from crosses between Pongsu Seribu 2 (Malaysian blast resistant cultivar) and
      Mahsuri (a susceptible rice cultivar), the genotypes for 13 designated multiplex
      SSR panels were determined. The genotyping assays were performed using a
      capillary-based ABIPRISM 3100 genetic analyser. The sizes of the SSRs alleles
      observed in the range from 79 to 324 bp. The observed marker segregation data
      were analysed using the Chi(2) test. A genetic linkage map covering ten
      chromosomes and comprising 63 polymorphic SSR markers was constructed, and the
      distorted loci were localised to linkage groups. The results indicated that
      distorted loci are presented on eight chromosomes.

PMID- 26318049
TI  - Chemical spying in coral reef fish larvae at recruitment.
AB  - When fish larvae recruit back to a reef, chemical cues are often used to find
      suitable habitat or to find juvenile or adult conspecifics. We tested if the
      chemical information used by larvae was intentionally produced by juvenile and
      adult conspecifics already on the reef (communication process) or whether the
      cues used result from normal biochemical processes with no active involvement by
      conspecifics ("spying" behavior by larvae). Conspecific chemical cues attracted
      the majority of larvae (four out of the seven species tested); although while
      some species were equally attracted to cues from adults and juveniles (Chromis
      viridis, Apogon novemfasciatus), two exhibited greater sensitivity to adult cues
      (Pomacentrus pavo, Dascyllus aruanus). Our results indicate also that spying cues
      are those most commonly used by settling fishes (C. viridis, P. pavo, A.
      novemfasciatus). Only one species (D. aruanus) preferred the odour of
      conspecifics that had had visual contact with larvae (communication). 

PMID- 26318050
TI  - Advanced MRI techniques to improve our understanding of experience-induced
      neuroplasticity.
AB  - Over the last two decades, numerous human MRI studies of neuroplasticity have
      shown compelling evidence for extensive and rapid experience-induced brain
      plasticity in vivo. To date, most of these studies have consisted of simply
      detecting a difference in structural or functional images with little concern for
      their lack of biological specificity. Recent reviews and public debates have
      stressed the need for advanced imaging techniques to gain a better understanding
      of the nature of these differences - characterizing their extent in time and
      space, their underlying biological and network dynamics. The purpose of this
      article is to give an overview of advanced imaging techniques for an audience of
      cognitive neuroscientists that can assist them in the design and interpretation
      of future MRI studies of neuroplasticity. The review encompasses MRI methods that
      probe the morphology, microstructure, function, and connectivity of the brain
      with improved specificity. We underline the possible physiological underpinnings
      of these techniques and their recent applications within the framework of
      learning- and experience-induced plasticity in healthy adults. Finally, we
      discuss the advantages of a multi-modal approach to gain a more nuanced and
      comprehensive description of the process of learning.

PMID- 26318051
TI  - Open Science CBS Neuroimaging Repository: Sharing ultra-high-field MR images of
      the brain.
AB  - Magnetic resonance imaging at ultra high field opens the door to quantitative
      brain imaging at sub-millimeter isotropic resolutions. However, novel image
      processing tools to analyze these new rich datasets are lacking. In this article,
      we introduce the Open Science CBS Neuroimaging Repository: a unique repository of
      high-resolution and quantitative images acquired at 7 T. The motivation for this
      project is to increase interest for high-resolution and quantitative imaging and
      stimulate the development of image processing tools developed specifically for
      high-field data. Our growing repository currently includes datasets from MP2RAGE
      and multi-echo FLASH sequences from 28 and 20 healthy subjects respectively.
      These datasets represent the current state-of-the-art in in-vivo relaxometry at 7
      T, and are now fully available to the entire neuroimaging community.

PMID- 26318053
TI  - Safety of bevacizumab in patients younger than 4 years of age.
AB  - PURPOSE: Limited data exist regarding the safety and efficacy of bevacizumab in
      pediatric patients under the age of 4 years. Here, we report a large cohort of
      pediatric patients under 4 years of age treated with bevacizumab. METHODS: The
      primary objective was to document adverse events with a possible relationship to
      bevacizumab. Patients (n = 16) were identified through retrospective chart review
      and harbored a variety of conditions (44% central nervous system (CNS) tumors,
      31% vascular anomalies, 13% neuroblastoma, 12% other). RESULTS: The median age
      was 34.3 months (range 4.9-47.3), including five patients <2 years of age.
      Patients received bevacizumab for a median duration of 6.2 months, alone or with
      chemotherapy, and a median dose of 9.25 mg/kg (range 7.0-11.8). Partial responses
      were seen in 19% of patients, and clinical improvements were seen in 69%. Adverse
      events known to be associated with bevacizumab occurred in 37%. Outcomes observed
      in this population resemble those reported for bevacizumab in older pediatric
      patients. The overall pattern and frequency of adverse events observed was
      similar to those seen in reports of older pediatric patients with a variety of
      conditions. The highest level of efficacy observed was seen among patients with
      vascular malformations or with low-grade CNS tumors. CONCLUSIONS: Our results
      suggest that the use of bevacizumab is safe for the youngest children.

PMID- 26318052
TI  - Levels and ecological risk assessment of metals in soils from a typical e-waste
      recycling region in southeast China.
AB  - Due to the high threat to human health and the ecosystem from metals, the levels
      and distribution of As, Hg, Cr, Co, Ni, Cu, Zn, Cd, Pb, Mn, V, Sn, Sb, Li and Be
      in various layers of soil from an e-waste recycling area in Guiyu, China were
      investigated. The extent of pollution from the metals in soil was assessed using
      enrichment factors (EFs) and the Nemerow pollution index (P N ). To determine the
      metals' integrated potential ecological risks, the potential ecological risk
      index (RI) was chosen. The concentrations of Hg, Ni, Cu, Cd, Pb, Sn and Sb were
      mainly enriched in the topsoil. EF values (2-5) of the elements Hg, Co, Ni, Zn,
      Sn, Li and Be revealed their moderate enrichment status in the topsoil, derived
      from e-waste recycling activities. P N presented a decreasing trend in different
      layers in the order topsoil (0-20 cm) > deep soil (100-150 cm) > middle soil (50
      100 cm) > shallow soil (20-50 cm). With higher potential ecological risk factor
      (E(i)), Hg and Cd are the main contributors to the potential ecological risk.
      With respect to the RI, all the values in soil from the study area exceeded 300,
      especially for the soil at sites S2, S4, S5, S7 and S8, where RI was greater than
      600. Therefore, immediate remediation of the contaminated soil is necessary to
      prevent the release of metals and potential ecological harm.

PMID- 26318054
TI  - 4-Aminoquinoline derivatives as novel Mycobacterium tuberculosis GyrB inhibitors:
      Structural optimization, synthesis and biological evaluation.
AB  - Mycobacterial DNA gyrase B subunit has been identified to be one of the
      potentially underexploited drug targets in the field of antitubercular drug
      discovery. In the present study, we employed structural optimization of the
      reported GyrB inhibitor resulting in synthesis of a series of 46 novel quinoline
      derivatives. The compounds were evaluated for their in vitro Mycobacterium
      smegmatis GyrB inhibitory ability and Mycobacterium tuberculosis DNA supercoiling
      inhibitory activity. The antitubercular activity of these compounds was tested
      over Mtb H37Rv strain and their safety profile was checked against mouse
      macrophage RAW 264.7 cell line. Among all, three compounds (23, 28, and 53)
      emerged to be active displaying IC50 values below 1 MUM against Msm GyrB and were
      found to be non-cytotoxic at 50 MUM concentration. Compound 53 was identified to
      be potent GyrB inhibitor with 0.86 +/- 0.16 MUM and an MIC (minimum inhibitory
      concentration) of 3.3 MUM. The binding affinity of this compound towards GyrB
      protein was analysed by differential scanning fluorimetry which resulted in a
      positive shift of 3.3  degrees C in melting temperature (Tm) when compared to the
      native protein thereby reacertaining the stabilization effect of the compound
      over protein.

PMID- 26318055
TI  - Novel spirobicyclic artemisinin analogues (artemalogues): Synthesis and antitumor
      activities.
AB  - The sesquiterpene lactone framework of artemisinin was used as a drug
      repositioning prototype for the development of novel antitumor drugs. Several
      series of novel artemisinin analogues (artemalogues) were designed and
      synthesized through 1,3-dipolar cycloaddition of artemisitene with nitrile oxides
      or nitrones. The isoxazolidine-containing spirobicyclic artemalogue 11b turns out
      to be the most potent with low micromolar IC50 values against all three tumor
      cells, which were at least 4- to 14-fold more potent than the parent artemisinin.

PMID- 26318057
TI  - Design, synthesis, and anticancer evaluation of long-chain alkoxylated mono
      carbonyl analogues of curcumin.
AB  - Curcumin is a nontoxic phenolic compound that modulates the activity of several
      cellular targets that have been linked with cancers and other chronic diseases.
      However, the efficacy of curcumin in the clinic has been limited by its poor
      bioavailability and rapid metabolism in vivo. We have previously reported the
      design and discovery of series of 5-carbon linker-containing mono-carbonyl
      analogues of curcumin (MACs) as anti-cancer agents. In continuation of our
      ongoing research, we designed and synthesized 37 novel long-chain alkoxylated
      MACs for anti-cancer evaluation here. The MTS assay was used to determine the
      cytotoxicity of compounds in gastrointestinal cancer cells. Compounds 5, 28, and
      29 showed strongest inhibition against gastric cancer cell proliferation and were
      subjected to further analysis. The effects of 5, 28, and 29 on cell apoptosis
      were measured by flow cytometry. Expression levels of Bcl-2, cleaved poly ADP
      ribose polymerase (PARP), and pro-caspase-3 were detected by western blotting.
      Compounds 5, 28, and 29 induced apoptosis in human gastric carcinoma cells,
      increased PARP cleavage, and decreased expression of Bcl-2 and pro-caspase-3
      protein. We then showed that compound 28, which possessed the strongest activity
      among the test compounds in vitro, exhibited significant tumor inhibition in
      SGC7901-driven xenograft mouse model. Taken together, the novel compound 28 could
      be further explored as an effective anticancer agent for the treatment of human
      gastric cancer.

PMID- 26318056
TI  - Investigation of new 2-aryl substituted Benzothiopyrano[4,3-d]pyrimidines as
      kinase inhibitors targeting vascular endothelial growth factor receptor 2.
AB  - Vascular Endothelial Growth Factor (VEGF) pathway has emerged as one of the most
      important positive modulators of Angiogenesis, a central process implicated in
      tumour growth and metastatic dissemination. This led to the design and
      development of anti-VEGF monoclonal antibodies and small-molecule ATP-competitive
      VEGFR-inhibitors. In this study, we describe the synthesis and the biological
      evaluation of novel 2-aryl substituted benzothiopyrano-fused pyrimidines 1a-i, 2a
      i and 3a-i. The ability of the compounds to target the VEGF pathway was
      determined in vitro exploiting the compounds' antiproliferative efficacy against
      HUVEC cells. The VEGFR-2 inhibition was confirmed by enzymatic assays on
      recombinant human kinase insert domain receptor (KDR), by cell-based phospho
      VEGFR-2 inhibition assays, and by ex vivo rat aortic ring tests. The selectivity
      profile of the best performing derivatives belonging to series 2 was further
      explored combining modeling studies and additional assays in a panel of human
      cell lines and other kinases.

PMID- 26318058
TI  - Episodic memory in normal aging and Alzheimer disease: Insights from imaging and
      behavioral studies.
AB  - Age-related cognitive changes often include difficulties in retrieving memories,
      particularly those that rely on personal experiences within their temporal and
      spatial contexts (i.e., episodic memories). This decline may vary depending on
      the studied phase (i.e., encoding, storage or retrieval), according to inter
      individual differences, and whether we are talking about normal or pathological
      (e.g., Alzheimer disease; AD) aging. Such cognitive changes are associated with
      different structural and functional alterations in the human neural network that
      underpins episodic memory. The prefrontal cortex is the first structure to be
      affected by age, followed by the medial temporal lobe (MTL), the parietal cortex
      and the cerebellum. In AD, however, the modifications occur mainly in the MTL
      (hippocampus and adjacent structures) before spreading to the neocortex. In this
      review, we will present results that attempt to characterize normal and
      pathological cognitive aging at multiple levels by integrating structural,
      behavioral, inter-individual and neuroimaging measures of episodic memory.

PMID- 26318059
TI  - Basic mechanisms of longevity: A case study of Drosophila pro-longevity genes.
AB  - Drosophila is one of the most convenient model organisms in the genetics of aging
      and longevity. Unlike the nematodes, which allow for the detection of new pro
      aging genes by knockout and RNAi-mediated knock-down, Drosophila also provides an
      opportunity to find new pro-longevity genes by driver-induced overexpression.
      Similar studies on other models are extremely rare. In this review, we focused on
      genes whose overexpression prolongs the life of fruit flies. The majority of
      longevity-associated genes regulates metabolism and stress resistance, and
      belongs to the IGF-1R, PI3K, PKB, AMPK and TOR metabolic regulation cluster and
      the FOXO, HDAC, p53 stress response cluster.

PMID- 26318060
TI  - Autophagy in bone: Self-eating to stay in balance.
AB  - Autophagy, a major catabolic pathway responsible of the elimination of damaged
      proteins and organelles, is now recognized as an anti-aging process. In addition
      to its basal role in cell homeostasis, autophagy is also a stress-responsive
      mechanism for survival purposes. Here, we review recent literature to highlight
      the autophagy role in the different bone cell types, i.e., osteoblasts,
      osteoclasts and osteocytes. We also discuss the effects of autophagy modulators
      in bone physiology and of bone anabolic compounds in autophagy. Finally, we
      analyzed studies regarding bone cell autophagy-deficient mouse models to obtain a
      more general view on how autophagy modulates bone physiology and pathophysiology,
      particularly during aging.

PMID- 26318061
TI  - Prevalence of Balantidium coli infection in sows in Hunan province, subtropical
      China.
AB  - Balantidium coli is a cosmopolitan parasitic-opportunistic pathogen that can be
      found throughout the world. However, little information is available about
      prevalence of B. coli in pigs in China. In the present study, the prevalence of
      B. coli in pigs was investigated in Hunan province, subtropical China, between
      January 2012 and August 2014. A total of 3925 diarrheic fecal samples from nine
      representative administrative regions in Hunan province, subtropical China, were
      examined for the presence of B. coli cysts and/or trophozoites using microscopy
      after sedimentation with water. The overall prevalence of B. coli in pigs was
      36.9 % (1450/3925). The present survey revealed high circulation of B. coli in
      pigs in Hunan province, subtropical China, which poses potential threats to human
      health. The results of the present investigation have important implications for
      the control of B. coli infections in pigs in Hunan province, subtropical China.
      To our knowledge, this is the first comprehensive report of B. coli prevalence in
      sows in Hunan province, subtropical China. 

PMID- 26318062
TI  - Left behind or moving forward? Effects of possible selves and strategies to
      attain them among rural Chinese children.
AB  - Are possible selves and strategies to attain them universally helpful even among
      children with few resources? We test this question in rural China. Rural Chinese
      children are commonly "left behind" (LB) by parents seizing economic
      opportunities by migrating, hoping the family will "move forward" and their
      children will attain their predestined better future. Media, teachers, and peers
      negatively represent LB children as unruly and undisciplined, with negative
      fates, making LB a negative stereotype that includes the idea of destiny or fate.
      Indeed, making the idea of LB salient increases children's fatalism (Study 1 n =
      144, Study 2 n = 124). However, having strategies to attain possible future
      selves predicts better in-class behavior, fewer depressive symptoms, and better
      exam performance even a year later and controlling for prior performance (Study 3
      n = 176, Study 4 n = 145). Possible selves have mixed effects, not always
      predicting better grades and undermining LB children's self-control. 

PMID- 26318063
TI  - Being bullied and feeling ashamed: Implications for eating psychopathology and
      depression in adolescent girls.
AB  - The current study examined the associations between peer victimization, body
      image shame, self-criticism, self-reassurance, depressive symptoms and eating
      psychopathology in 609 female adolescents. Correlational analyses showed that
      being the victim of bullying was positively associated with body image shame,
      self-criticism, with low self-reassurance, depressive symptoms and eating
      psychopathology. A path analysis indicated that victimization experiences were
      associated with increased depressive symptoms partially through increased levels
      of body image shame, and a severe form of self-criticism - hated self. Body image
      shame and hated-self self-criticism fully mediated the association between
      victimization experiences eating psychopathology. The tested model accounted for
      a total of 51% of depressive symptoms variance and for 52% of eating
      psychopathology variance. These findings may have important intervention and
      prevention implications, by suggesting that bullying experiences fuel body image
      shame and consequent self-directed hostility and anger, which, in turn, predict
      increased depressive symptomatology and eating psychopathology in female
      adolescents. 

PMID- 26318064
TI  - The effect of glycine replacement with flexible omega-amino acids on the
      antimicrobial and haemolytic activity of an amphipathic cyclic heptapeptide.
AB  - Although cyclic peptide structures are usually investigated as highly constrained
      scaffolds, cyclic antimicrobial peptides of natural origin often feature flexible
      residues. Hereby we report our findings concerning a structure-activity study
      conducted on a model sequence by replacing a glycine residue with a variety of
      flexible residues (i.e. omega-amino and alpha,omega-diamino acids). The resulting
      library has been tested for antimicrobial activity against a wide range of
      clinically relevant pathogens as well as for toxicity to red blood cells.
      Circular dichroism and molecular modelling have been used to study changes in
      conformation. Increments as high as 16-fold in antimicrobial activity (as
      effective as lipidation) and >2-fold in haemolytic EC50 values were observed.
      Interestingly, secondary structures can be stabilized by increasing, rather than
      decreasing, ring flexibility. 

PMID- 26318065
TI  - Aminothiazoles: Hit to lead development to identify antileishmanial agents.
AB  - As part of Drugs for Neglected Diseases initiative's lead optimization program
      for the development of new chemical entities to treat visceral leishmaniasis
      (VL), a series of aminothiazoles were synthesized and screened for in vitro
      efficacy, solubility and microsomal stability. The primary aim of identifying a
      lead structure with sub-micromolar activity was achieved. Out of 43 compounds
      synthesized, 16 compounds showed in vitro activity at less than 1 MUM against VL.
      Compound 32 showed excellent antileishmanial potency (IC50 = 3 nM) and had all
      the acceptable properties except for metabolic instability. Blocking the
      metabolic soft spots in compound 32, where the 4-methoxy pyridine substituent was
      replaced by 5-ethoxy group, led to compound 36 (IC50 = 280 nM) with improved
      stability. To understand the disposition of 36, in vivo pharmacokinetic study was
      conducted in a mouse model. Compound 36 showed high clearance (91 mL/min/kg);
      short half-life (0.48 h) after intravenous administration (1 mg/kg) and exposure
      (AUC0-24) following oral administration was 362 ng h/mL with absolute
      bioavailability of 8%. To summarize, 43 analogs were synthesized out of which 15
      compounds showed very potent sub-nanomolar efficacy in in vitro systems but the
      liability of metabolic instability seemed to be the major challenge for this
      chemical class and remains to be addressed.

PMID- 26318066
TI  - Synthesis and biological evaluation of ring A and/or C expansion and opening
      echinocystic acid derivatives for anti-HCV entry inhibitors.
AB  - Echinocystic acid (EA), a naturally occurring oleanane-type triterpene isolated
      from Dipsacus asperoides, was found to have anti-HCV entry activity in our
      previous study. Expansion of triterpene structural diversity, including the ring
      A and/or C expansion and opening, was performed. To elucidate the pharmacophore
      of EA, seven lactones (8, 16, 17, 24, 26, 35 and 41), three 3,28-dioic acids (9,
      36 and 42) and two pentols (10 and 27) were synthesized. The anti-HCV entry
      activities of those derivatives, along with their parental compound EA and
      analogs alpha,beta-unsaturated ketone (18), were evaluated. All the products
      showed no improvement but detrimental effect on potency of EA. The results
      demonstrated that ring A and C of EA are highly conserved, indicating the steric
      effects of the rigid skeleton have a profound effect on the potency. 

PMID- 26318067
TI  - Discovery of 4-arylamido 3-methyl isoxazole derivatives as novel FMS kinase
      inhibitors.
AB  - A series of 4-arylamido 3-methyl isoxazoles were synthesized and evaluated for
      their antiproliferative activities against the A375P melanoma and U937
      hematopoietic cell lines. Most compounds showed selective antiproliferative
      activity toward the U937 cell line and the activities were better than that of
      sorafenib, the reference standard. Derivatives were made as amide 5a-b, 6a-o and
      urea 7a-n, 8a-g with hydrophobic moieties, and one of the most potent inhibitor
      6a, 5-methyl-N-(2-methyl-5-(3-(4-methylpiperazin-1-yl)-5
      (trifluoromethyl)benzamido)phenyl)isoxazole-4-carboxamide was found to be very
      potent inhibitor of FMS kinase (GI50 = 0.016 MUM, IC50 = 9.95 nM) with excellent
      selectivity profiles and is a promising candidate for further development in
      therapeutics for cancer.

PMID- 26318068
TI  - Current developments of coumarin-based anti-cancer agents in medicinal chemistry.
AB  - Cancer is one of the leading health hazards and the prominent cause of death in
      the world. A number of anticancer agents are currently in clinical practice and
      used for treatment of various kinds of cancers. There is no doubt that the
      existing arsenal of anticancer agents is insufficient due to the high incidence
      of side effects and multidrug resistance. In the efforts to develop suitable
      anticancer drugs, medicinal chemists have focused on coumarin derivatives.
      Coumarin is a naturally occurring compound and a versatile synthetic scaffold
      possessing wide spectrum of biological effects including potential anticancer
      activity. This review article covers the current developments of coumarin-based
      anticancer agents and also discusses the structure-activity relationship of the
      most potent compounds. 

PMID- 26318069
TI  - Synthesis and evaluation of new tyrosyl-tRNA synthetase inhibitors as
      antibacterial agents based on a N2-(arylacetyl)glycinanilide scaffold.
AB  - Tyrosyl-tRNA synthetase (TyrRS), an essential enzyme in bacterial protein
      biosynthesis, is an attractive therapeutic target for finding novel antibacterial
      agents, and a series of N2-(arylacetyl)glycinanilides has been herein synthesized
      and identified as TyrRS inhibitors. These efforts yielded several compounds, with
      IC50 in the low micromolar range against TyrRS from Staphylococcus aureus. Out of
      the obtained compounds, 3ap is the most active and exhibits excellent activity
      against both Gram-positive (S. aureus) and Gram-negative (Escherichia coli and
      Pseudomonas aeruginosa) bacterial strains. In comparison with the parent scaffold
      3-arylfuran-2(5H)-one, N2-(arylacetyl)glycinanilide significantly improved the
      potency against Gram-negative bacterial strains, indicating that this scaffold
      offers a significant potential for developing new antibacterial drugs.

PMID- 26318070
TI  - Synthesis, anti-tobacco mosaic virus and cucumber mosaic virus activity, and 3D
      QSAR study of novel 1,4-pentadien-3-one derivatives containing 4-thioquinazoline
      moiety.
AB  - A series of novel 1,4-pentadien-3-one derivatives containing 4-thioquinazoline
      moiety were designed and synthesized. Antiviral bioassay results indicated that
      most of the title compounds exhibited excellent antiviral activities against
      tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) in vivo. Among the
      title compounds, 7j exhibited the best curative activity against TMV, with a half
      maximal effective concentration (EC50) value of 213.5 MUg/mL, which was better
      than that of ningnanmycin (270.9 MUg/mL). Meanwhile, 7a showed remarkable
      protection activity against TMV and curative activity against CMV, with EC50
      values of 124.3 and 365.5 MUg/mL, respectively, which were superior to those of
      ningnanmycin (195.1 and 404.9 MUg/mL, respectively). Comparative molecular field
      analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA)
      models were generated on the basis of the curative activities against TMV and
      exhibited good predictive abilities with cross-validated q(2) and non-cross
      validated r(2) values for CoMFA and CoMSIA of 0.548, 0.647 and 0.994, 0.993,
      respectively. These results provided a practical tool for guiding the design and
      synthesis of novel and more potent 1,4-pentadien-3-one derivatives containing 4
      thioquinazoline moiety.

PMID- 26318071
TI  - IL-10-producing forkhead box protein 3-negative regulatory T cells inhibit B-cell
      responses and are involved in systemic lupus erythematosus.

PMID- 26318072
TI  - New and future strategies to improve asthma control in children.
AB  - Symptomatic asthma in childhood has lifelong effects on lung function and disease
      severity, emphasizing the need for improved pediatric asthma control. Control of
      pediatric risk and impairment domains can be achieved through increased
      medication adherence or new therapeutic strategies. Developing electronic
      monitoring device technology with reminders might be a key noninvasive resource
      to address poor adherence in children and adolescents in a clinical setting. In
      patients who have persistently poor control despite optimal medication
      compliance, newly emerging pharmaceuticals, including inhaled therapies and
      biologics, might be key to their treatment. However, barriers exist to their
      development in the pediatric population, and insights must be drawn from adult
      studies, which has its own unique limitations. Biomarkers to direct the use of
      such potentially expensive therapies to those patients most likely to benefit are
      imperative. In this review the current literature regarding strategies to improve
      pediatric asthma control is addressed with the goal of exploring the potential
      and pitfalls of strategies that might be available in the near future. 

PMID- 26318073
TI  - Proton pump inhibitor-responsive esophageal eosinophilia does not preclude food
      responsive eosinophilic esophagitis.

PMID- 26318074
TI  - Advancing metabolic engineering through systems biology of industrial
      microorganisms.
AB  - Development of sustainable processes to produce bio-based compounds is necessary
      due to the severe environmental problems caused by the use of fossil resources.
      Metabolic engineering can facilitate the development of highly efficient cell
      factories to produce these compounds from renewable resources. The objective of
      systems biology is to gain a comprehensive and quantitative understanding of
      living cells and can hereby enhance our ability to characterize and predict
      cellular behavior. Systems biology of industrial microorganisms is therefore
      valuable for metabolic engineering. Here we review the application of systems
      biology tools for the identification of metabolic engineering targets which may
      lead to reduced development time for efficient cell factories. Finally, we
      present some perspectives of systems biology for advancing metabolic engineering
      further. 

PMID- 26318075
TI  - Building cellular pathways and programs enabled by the genetic diversity of allo
      genomes and meta-genomes.
AB  - Engineering pathways, programs and traits that require interactions of many,
      often unknown, genes requires advanced engineering strategies in the context of
      synthetic biology. Such strategies derive from three basic requirements: a
      suitably enlarged gene pool compared to the parent strain; a method of
      identification and incorporation of genetic-element interactions to generate the
      multigenic pathway or trait; and a process of selection of individuals from
      diverse strain populations that benefit the desirable pathway or trait. We review
      potential methods utilized in such advanced engineering strategies, emphasizing
      methods that explore the genomic diversity of allogeneic DNA (the allogenome) or
      the metagenome. We also propose a modular iterative approach for developing
      multigenic cellular traits. 

PMID- 26318076
TI  - Improving prediction fidelity of cellular metabolism with kinetic descriptions.
AB  - Several modeling frameworks for describing and redirecting cellular metabolism
      have been developed keeping pace with the rapid development in high-throughput
      data generation and advances in metabolic engineering techniques. The
      incorporation of kinetic information within stoichiometry-only modeling
      techniques offers potential advantages for improved phenotype prediction and
      consequently more precise computational strain design. In addition to substrate
      level kinetic regulatory information, the integration of a number of additional
      layers of regulation at the transcription, translation, and post-translation
      levels is sought after by many research groups. However, the practical
      integration of these complex biological processes into a unified framework
      amenable to design remains an ongoing challenge. 

PMID- 26318077
TI  - Bio-based production of monomers and polymers by metabolically engineered
      microorganisms.
AB  - Recent metabolic engineering strategies for bio-based production of monomers and
      polymers are reviewed. In the case of monomers, we describe strategies for
      producing polyamide precursors, namely diamines (putrescine, cadaverine, 1,6
      diaminohexane), dicarboxylic acids (succinic, glutaric, adipic, and sebacic
      acids), and omega-amino acids (gamma-aminobutyric, 5-aminovaleric, and 6
      aminocaproic acids). Also, strategies for producing diols (monoethylene glycol,
      1,3-propanediol, and 1,4-butanediol) and hydroxy acids (3-hydroxypropionic and 4
      hydroxybutyric acids) used for polyesters are reviewed. Furthermore, we review
      strategies for producing aromatic monomers, including styrene, p-hydroxystyrene,
      p-hydroxybenzoic acid, and phenol, and propose pathways to aromatic polyurethane
      precursors. Finally, in vivo production of polyhydroxyalkanoates and recombinant
      structural proteins having interesting applications are showcased. 

PMID- 26318078
TI  - Poor performance status (PS) is an indication for an aggressive approach to
      neoadjuvant chemotherapy in patients with advanced epithelial ovarian cancer
      (EOC).
AB  - BACKGROUND: Some guidelines suggest that poor performance status (PS) is a
      contraindication to 1st line chemotherapy. Poor PS is a known adverse prognostic
      factor in advanced epithelial ovarian cancer (EOC). We show in this retrospective
      analysis that 1st line chemotherapy in this patient group is not only safe but is
      associated with good outcomes. PATIENTS AND METHODS: A retrospective review of
      114 patients with stage III/IV EOC, who presented with a PS >=3 at diagnosis and
      treated as inpatients with upfront platinum-based chemotherapy between 2000 and
      2013, at the Royal Marsden Hospital, was conducted. The association between
      clinical parameters and the likelihood of completion of chemotherapy and overall
      survival (OS) was assessed. RESULTS: 66% of patients completed >=6cycles of
      platinum-based chemotherapy. Prognostic factors for completion of chemotherapy
      were improvement of PS during hospital stay (p<0.001) and doublet-chemotherapy
      with carboplatin/paclitaxel compared to single-agent carboplatin (p=0.004). A
      negative trend for completion of treatment was seen for patients with low albumin
      (<25g/l) and low CA125 levels at baseline. The median OS for all patients was
      13.1months (95% CI: 10.4-15.8) and 21.2months (95% CI: 16.5-25.8) for those who
      completed 6cycles of chemotherapy. CONCLUSION: Upfront platinum-based
      chemotherapy is feasible, beneficial and tolerable for the majority of patients
      with advanced EOC and poor PS. Guidelines suggesting that best supportive care is
      the preferred option for poor PS patients with solid tumours should be revised to
      exclude those with advanced EOC. An aggressive approach utilising neoadjuvant
      carboplatin plus paclitaxel should be regarded as standard of care.

PMID- 26318079
TI  - CXCL10 in psoriasis.
AB  - Chemokine (C-X-C motif) ligand (CXCL)10 is involved in the pathogenesis of
      psoriasis. It has been demonstrated that chemokine (C-X-C motif) receptors
      (CXCR)3 and CXCL10 were detected in keratinocytes and the dermal infiltrate
      obtained from active psoriatic plaques and that successful treatment of active
      plaques decreased the expression of CXCL10. Elevated CXCL10 serum levels have
      been shown in patients with psoriasis, with a type 1 T helper cells immune
      predominance at the beginning of the disease, while a decline of this chemokine
      has been evidenced later, in long lasting psoriasis. Circulating CXCL10 is
      significantly higher in patients with psoriasis in the presence of autoimmune
      thyroiditis. It has been hypothesized that CXCL10 could be a good marker to
      monitor the activity or progression of psoriasis. Efforts have been made to
      modulate or inhibit the CXCR3/CXCL10 axis in psoriasis to modify the course of
      the disease. 

PMID- 26318080
TI  - Moral Disengagement, Anticipated Social Outcomes and Adolescents' Alcohol Use:
      Parallel Latent Growth Curve Analyses.
AB  - Moral disengagement is a social cognitive process that has been extensively
      applied to transgressive behaviors, including delinquency, aggression and illicit
      substance use. However, there has been limited research on moral disengagement as
      it relates to underage drinking. The current study aimed to examine moral
      disengagement contextualized to underage drinking and its longitudinal
      relationship to alcohol use. Moreover, the social context in which adolescent
      alcohol use typically occurs was also considered, with a specific emphasis on the
      social sanctions, or social outcomes, that adolescents anticipate receiving from
      friends for their alcohol use. Adolescents were assessed across three time
      points, 8 months apart. The longitudinal sample consisted of 382 (46% female)
      underage drinkers (12-16 years at T1). Parallel latent growth curve analysis was
      used to examine the bi-directional influence of initial moral disengagement,
      anticipated social outcomes, and alcohol use on subsequent growth in moral
      disengagement, anticipated social outcomes and alcohol use. The interrelation of
      initial scores and growth curves was also assessed. The findings revealed that,
      in the binary parallel analyses, initial moral disengagement and anticipated
      social outcomes both significantly predicted changes in alcohol use across time.
      Moreover, initial anticipated social outcomes predicted changes in moral
      disengagement. These findings were not consistently found when all three process
      analyses were included in a single model. The results emphasize the impact of
      social context on moral disengagement and suggest that by targeting adolescents'
      propensity to justify or excuse their drinking, as well as the social outcomes
      adolescents anticipate for being drunk, it may be possible to reduce their
      underage drinking.

PMID- 26318081
TI  - The Incremental Hospital Cost and Length-of-Stay Associated With Treating Adverse
      Events Among Medicare Beneficiaries Undergoing THA During Fiscal Year 2013.
AB  - This paper estimates the incremental hospital resource consumption associated
      with treating selected adverse events experienced by Medicare beneficiaries (MBs)
      undergoing total hip arthroplasty (THA). This retrospective study, using the
      Medicare Provider Analysis and Review file, identified 174,167 MBs who underwent
      THA in 2013. Overall, 20.16% of MB undergoing THA experienced at least one
      adverse event. MB experiencing any adverse event consumed significantly higher
      hospital cost ($3429) and had longer length of stays (1.0 day). The risk-adjusted
      incremental cost of treating adverse events ranged from a high of $27,116
      (pneumonia) to a low of $2626 (hemorrhage or post-operative shock requiring
      transfusion). Most major adverse events occurred infrequently, however when
      adverse events occurred, they add substantially to the hospital resource costs of
      treating MB.

PMID- 26318082
TI  - Patient-Specific Total Knees Demonstrate a Higher Manipulation Rate Compared to
      "Off-the-Shelf Implants".
AB  - Patient-specific total knee replacements have been designed in hopes of providing
      better functional outcomes compared to "off-the-shelf" implants in primary total
      knee arthroplasty (TKA). We prospectively evaluated manipulation rates and
      clinical outcomes of 21 patient-specific TKAs matched with 42 posterior
      stabilized and 11 cruciate-retaining "off-the-shelf" TKAs. Postoperatively, the
      patient-specific group had a range of motion significantly less than both control
      groups (P<0.01). Six of the 21 (28.6%) patient-specific TKAs required
      manipulation to improve range of motion. No manipulations were reported in either
      control groups. At minimum two-year follow-up the patient-specific TKAs had
      similar motion, but worse satisfaction and KSS pain scores. Radiographic analysis
      provided no insight to the cause of stiffness. Early manipulation is recommended
      for stiffness with patient-specific TKA. 

PMID- 26318083
TI  - Validating a Modified Circle Theorem Method for the Measurement of Acetabular Cup
      Anteversion on Plain Radiography with Intra-Operative Data from Robotic Assisted
      Total Hip Arthroplasty.
AB  - This study aims to validate a modified circle theorem method for the calculation
      of true version of the acetabular component on anteroposterior x-rays with intra
      operative version data derived from robotic assisted total hip arthroplasty
      (THA). Planar anteversion measurements recorded intraoperatively in 80 THAs were
      correlated to measurements on anteroposterior radiographs. The mean anteversion
      of the cohort measured by the robotic system and on plain radiography was 21.2
      degrees  +/- 2.0 degrees  and 19.9 degrees  +/- 3.4 degrees  respectively and
      97.5% of cases were in a 30% relative error. The correlation between the true and
      planar measurements of anteversion on plain radiographs was strong (Pearson
      correlation coefficient of 0.9422). We conclude that the circle theorem method
      can be validated with data from robotic guided THA. 

PMID- 26318084
TI  - Serum Metal Ion Levels Following Total Hip Arthroplasty With Modular Dual
      Mobility Components.
AB  - Dual mobility acetabular components can reduce the incidence of total hip
      arthroplasty (THA) instability. Modular dual mobility (MDM) components facilitate
      acetabular component implantation. However, corrosion can occur at modular
      junctions. Serum cobalt and chromium levels and Oxford scores were obtained at
      minimum two year follow-up for 100 consecutive patients who had THA with MDM
      components. Average Oxford score was 43 (range 13-48). Average serum cobalt and
      chromium values were 0.7 mcg/L (range, 0.0 to 7.0) and 0.6 mcg/L (range, 0.1 to
      2.7), respectively. MARS MRI was performed for four patients with pain and
      elevated serum cobalt levels. Two of these studies were consistent with adverse
      local tissue reaction. We recommend use of MDM implants in only patients at high
      risk for dislocation following THA. 

PMID- 26318085
TI  - Cost-efficient FPGA implementation of basal ganglia and their Parkinsonian
      analysis.
AB  - The basal ganglia (BG) comprise multiple subcortical nuclei, which are
      responsible for cognition and other functions. Developing a brain-machine
      interface (BMI) demands a suitable solution for the real-time implementation of a
      portable BG. In this study, we used a digital hardware implementation of a BG
      network containing 256 modified Izhikevich neurons and 2048 synapses to reliably
      reproduce the biological characteristics of BG on a single field programmable
      gate array (FPGA) core. We also highlighted the role of Parkinsonian analysis by
      considering neural dynamics in the design of the hardware-based architecture.
      Thus, we developed a multi-precision architecture based on a precise analysis
      using the FPGA-based platform with fixed-point arithmetic. The proposed embedding
      BG network can be applied to intelligent agents and neurorobotics, as well as in
      BMI projects with clinical applications. Although we only characterized the BG
      network with Izhikevich models, the proposed approach can also be extended to
      more complex neuron models and other types of functional networks. 

PMID- 26318086
TI  - Pushing, pulling, and squeezing our way to understanding mechanotransduction.
AB  - Mechanotransduction is often described in the context of force-induced changes in
      molecular conformation, but molecular-scale mechanical stimuli arise in vivo in
      the context of complex, multicellular tissue structures. For this reason, we
      highlight and review experimental methods for investigating mechanotransduction
      across multiple length scales. We begin by discussing techniques that probe the
      response of individual molecules to applied force. We then move up in length
      scale to highlight techniques aimed at uncovering how cells transduce mechanical
      stimuli into biochemical activity. Finally, we discuss approaches for determining
      how these stimuli arise in multicellular structures. We expect that future work
      will combine techniques across these length scales to provide a more
      comprehensive understanding of mechanotransduction. 

PMID- 26318087
TI  - Enhancing protein function prediction with taxonomic constraints--The Argot2.5
      web server.
AB  - Argot2.5 (Annotation Retrieval of Gene Ontology Terms) is a web server designed
      to predict protein function. It is an updated version of the previous Argot2
      enriched with new features in order to enhance its usability and its overall
      performance. The algorithmic strategy exploits the grouping of Gene Ontology
      terms by means of semantic similarity to infer protein function. The tool has
      been challenged over two independent benchmarks and compared to Argot2, PANNZER,
      and a baseline method relying on BLAST, proving to obtain a better performance
      thanks to the contribution of some key interventions in critical steps of the
      working pipeline. The most effective changes regard: (a) the selection of the
      input data from sequence similarity searches performed against a clustered
      version of UniProt databank and a remodeling of the weights given to Pfam hits,
      (b) the application of taxonomic constraints to filter out annotations that
      cannot be applied to proteins belonging to the species under investigation. The
      taxonomic rules are derived from our in-house developed tool, FunTaxIS, that
      extends those provided by the Gene Ontology consortium. The web server is free
      for academic users and is available online at
      http://www.medcomp.medicina.unipd.it/Argot2-5/. 

PMID- 26318088
TI  - Fabrication and characterization of nano-fibrous bilayer composite for skin
      regeneration application.
AB  - Full thickness wound healing with minimal scarring and complete restoration of
      normal skin properties still remains as a clinical challenge. In this study, a
      bilayer skin substitute has been fabricated to biomimic the microstructure of
      natural extracellular matrix of the skin. Human amniotic membrane (HAM) and silk
      fibroin nano-fibers were combined to produce bilayer construct, which was further
      treated and characterized. HAM was obtained from healthy mothers and de
      epithelized by means of fine enzymatic method to preserve the extracellular
      structure. Fibroin protein was extracted from fresh Bombyx mori cocoons and
      transformed to uniform nano-fiberous structure, which was used as a coating layer
      on the de-epithelized membrane. Surface modification through oxygen plasma
      treatment was attempted to further induce hydrophilicity. Subsequently, scaffolds
      were fully characterized in terms of morphology, mechanical properties,
      hydrophilicity and cell culture response. Histological and immunohistological
      staining demonstrated localization of fibronectin, cell denudation and structural
      integrity of HAM after de-epithelization. Scanning electron microscopy images
      showed bead-free silk fibroin nano-fibers with the average diameter of 250nm.
      Water contact angle of bilayer scaffolds reduced dramatically to 26.34 degrees 
      after oxygen plasma treatment, which is correlated with more hydrophilic surface.
      Due to fibroin nano-fiber coating, mechanical properties of HAM improved
      significantly. Tensile Young's modulus and tensile strength increased from
      16.14MPa and 68.46MPa to 25.69MPa and 108.03MPa, respectively. 14days in vitro
      cultivation of mouse embryonic fibroblasts on the scaffolds revealed that bilayer
      scaffolds are able to support cell attachment and proliferation. Plasma-etched
      scaffolds provided the best niche for cell-matrix crosstalk by allowing cells to
      penetrate beneath the pores and to integrate in fibers direction. The obtained
      results suggest that the presented nano-fibrous bilayer composite based on HAM is
      a potential substitute for skin regeneration application.

PMID- 26318089
TI  - Uncovering mechanosensing mechanisms at the single protein level using magnetic
      tweezers.
AB  - Mechanosensing of the micro-environments has been shown to be essential for cell
      survival, growth, differentiation and migration. The mechanosensing pathways are
      mediated by a set of mechanosensitive proteins located at focal adhesion and cell
      cell adherens junctions as well as in the cytoskeleton network. Here we review
      the applications of magnetic tweezers on elucidating the molecular mechanisms of
      the mechanosensing proteins. The scope of this review includes the principles of
      the magnetic tweezers technology, theoretical analysis of force-dependent
      stability and interaction of mechanosensing proteins, and recent findings
      obtained using magnetic tweezers. 

PMID- 26318090
TI  - In search of coding and non-coding regions of DNA sequences based on balanced
      estimation of diffusion entropy.
AB  - Identification of coding regions in DNA sequences remains challenging. Various
      methods have been proposed, but these are limited by species-dependence and the
      need for adequate training sets. The elements in DNA coding regions are known to
      be distributed in a quasi-random way, while those in non-coding regions have
      typical similar structures. For short sequences, these statistical
      characteristics cannot be extracted correctly and cannot even be detected. This
      paper introduces a new way to solve the problem: balanced estimation of diffusion
      entropy (BEDE). 

PMID- 26318091
TI  - Sequencing new agents after docetaxel in patients with metastatic castration
      resistant prostate cancer.
AB  - BACKGROUND: Two new hormonal agents (NHAs), abiraterone and enzalutamide, and one
      chemotherapeutic agent, cabazitaxel (CABA) improved overall survival (OS) in
      patients with metastatic castration-resistant prostate cancer (mCRPC) who
      progress after docetaxel. Although several analyses of patient cohorts receiving
      a sequence of two different new agents (NAs) after docetaxel have been published,
      no definite conclusions can be drawn regarding the best treatment strategy.
      MATERIALS AND METHODS: All published studies reporting monthly OS rates of mCRPC
      patients receiving third-line NA after having previously received docetaxel and
      another NA have been analyzed. The treatments were merged into three groups: one
      NHA followed by another, one NHA followed by CABA, and CABA followed by one NHA.
      The cumulative monthly OS rates in each group were determined using a weighted
      average approach. RESULTS: Thirteen retrospective studies including 1016 patients
      who received NHA/NHA (469), NHA/CABA (318) or CABA/NHA (229) were evaluated. The
      12-month OS rates were 28.5%, 61.3%, and 76.4%, respectively. There were no
      statistically significant differences in terms of known prognostic factors.
      CONCLUSIONS: Although the retrospective nature of the studies and potential
      selection biases, our data seem to confirm the potential cumulative survival
      benefit of using the NAs sequentially after docetaxel. There was no clear
      superiority of any one of the three strategies, but a sequence that includes CABA
      seems to suggest a possible OS advantage.

PMID- 26318092
TI  - Treatment of HER2 positive advanced breast cancer with T-DM1: A review of the
      literature.
AB  - BACKGROUND: Trastuzumab emtansine (T-DM1), a new agent developed for the
      treatment of HER2-positive breast cancer, is an antibody-drug conjugate with a
      complex compound obtained by the conjugation of trastuzumab, a stable thioether
      linker, and the potent cytotoxic drug maytansine-derivate(DM1), which inhibits
      cell division and induces cell death. FIELD OF STUDY: PubMed database, ESMO,
      ASCO, San Antonio Breast Cancer Symposium Meeting abstracts and
      clinicaltrials.gov were searched using the terms "Anti-HER2 treatment breast
      cancer and trastuzumab emtansine (T-DM1) "; papers considered relevant for the
      aim of this review were selected. FINDINGS/RESULTS: The phase I trials have
      determined the safe dosing range of T-DM1, established at 3.6 mg/kg every 3
      weeks. The phase III randomized EMILIA and TR3RESA trials have shown that T-DM1
      provides objective tumor responses and significantly improves progression free
      survival and overall survival in HER2-positive metastatic breast cancer patients
      previously treated with anti-HER2-based regimens. The ongoing phase III trials
      KAITLIN and KATHERINE will give us further information about the place T-DM1
      should occupy in the treatment of patients with early stage HER2-positive breast
      cancer. In this review we analyze the most relevant clinical trials conducted
      with T-DM1 and the role of this compound in the management of advanced breast
      cancer. CONCLUSION: T-DM1 has shown clinically relevant activity in the treatment
      of HER2-positive breast cancer patients after progression on trastuzumab and
      taxane based therapy, both in the second line treatment setting and after early
      relapse on adjuvant trastuzumab therapy. This is accompanied by a favorable
      safety and tolerability profile.

PMID- 26318093
TI  - A review of monoclonal antibody therapies in lymphoma.
AB  - Monoclonal antibodies (moAb) represent a novel way of delivering therapy through
      specific target antigens expressed on lymphoma cells and minimizes the collateral
      damage that is common with conventional chemotherapy. The paradigm of this
      approach is the targeting of CD20 by rituximab. Since its FDA approval in 1997,
      rituximab has become the standard of care in almost every line of therapy in most
      B-cell lymphomas. This review will briefly highlight some of the key rituximab
      trials while looking more closely at the evidence that is bringing other
      antibodies, including next generation anti-CD20 moAbs, and anti-CD30 moAbs, among
      others to the forefront of lymphoma therapy. 

PMID- 26318094
TI  - Afatinib: An overview of its clinical development in non-small-cell lung cancer
      and other tumors.
AB  - Afatinib is an oral, irreversible, tyrosine kinase inhibitor (TKI) of EGFR, HER2
      and HER4. According to phase I studies, the recommended dose of afatinib was 50mg
      daily. Rash, acne, diarrhea and stomatitis were the most common adverse events.
      Afatinib failed to demonstrate an improvement in overall survival in unselected
      heavily pretreated NSCLC patients (Lux-Lung-1). On the contrary, the Lux-Lung-3
      and -6 trials met the primary end point, demonstrating a significant increase in
      terms of PFS with afatinib compared with chemotherapy in the first line treatment
      of EGFR mutant patients. Moreover, in both studies, afatinib improved overall
      survival in patients with exon 19 EGFR deletion (31.7 vs 20.7 months; HR: 0.59,
      p=0.0001). The results of ongoing randomized trials should further clarify the
      efficacy of afatinib compared with first-generation TKIs in advanced NSCLC, its
      activity in the adjuvant and neoadjuvant settings, as well as its efficacy in
      other tumors. 

PMID- 26318095
TI  - Oral toxicity management in head and neck cancer patients treated with
      chemotherapy and radiation: Dental pathologies and osteoradionecrosis (Part 1)
      literature review and consensus statement.
AB  - Radiotherapy alone or in combination with chemotherapy and/or surgery is the
      typical treatment for head and neck cancer patients. Acute side effects (such as
      oral mucositis, dermatitis, salivary changes, taste alterations, etc.), and late
      toxicities in particular (such as osteo-radionecrosis, hypo-salivation and
      xerostomia, trismus, radiation caries etc.), are often debilitating. These
      effects tend to be underestimated and insufficiently addressed in the medical
      community. A multidisciplinary group of head and neck cancer specialists met in
      Milan with the aim of reaching a consensus on clinical definitions and management
      of these toxicities. The Delphi Appropriateness method was used for developing
      the consensus, and external experts evaluated the conclusions. This paper
      contains 10 clusters of statements about the clinical definitions and management
      of head and neck cancer treatment sequels (dental pathologies and osteo
      radionecroses) that reached consensus, and offers a review of the literature
      about these topics. The review was split into two parts: the first part dealt
      with dental pathologies and osteo-radionecroses (10 clusters of statements),
      whereas this second part deals with trismus and xerostomia. 

PMID- 26318096
TI  - Jump in the fire--heat shock proteins and their impact on ovarian cancer therapy.
AB  - Ovarian cancer (OC) is a major problem in gynecological oncology. Options for
      diagnosis and treatment of advanced stages and thus for patient prognosis have
      not been improved substantially over the past decades. Heat shock proteins (HSP)
      are characterized as stress-induced molecular chaperones performing cell survival
      factor functions. In cancer cells, various crucial and clinically important cell
      responses are vitally influenced and modulated by HSPs, e.g., cell growth and
      treatment resistance. Despite the limited knowledge on HSPs in OC progression,
      their roles as biomarkers, prognostic factors and their drug target properties
      appears promising for future clinical applications and therapeutic approaches. 

PMID- 26318097
TI  - Regulatory roles and therapeutic potential of microRNA in sarcoma.
AB  - PURPOSE: MicroRNAs (miRNAs) are single-stranded noncoding RNAs involved in
      various biological processes, including cell differentiation and development.
      They play multiple key roles as tumour suppressors, oncogenes or both in
      particular cases. This review aims to summarise current findings of the
      expression of miRNAs and their role in clinical oncology. Current knowledge
      regarding the involvement of miRNAs in different sarcoma subtypes will be
      assessed, in conjunction with their potential application as therapeutic targets.
      METHODS: Relevant articles in scientific databases were identified using a
      combination of search terms, including "microRNA," "deregulation," "sarcoma," and
      "targeted therapy". These databases included Medline, Embase, Cochrane Review,
      Pubmed and Scopus. RESULTS: Aberrant miRNA expression patterns have been
      identified in a range of sarcoma subtypes, and differences in miRNA expression
      profiles between malignant cells and their normal counterparts suggests that
      miRNAs play key roles in sarcoma development. The identification of unique miRNA
      patterns in individual tumour types could possibly be used as a diagnostic tool
      in sarcoma. Moreover, identification of these miRNAs provides novel targets for
      the development of therapeutic strategies in distinct sarcoma subtypes.
      CONCLUSION: miRNAs hold significant potential as diagnostic biomarkers, as well
      as therapeutic targets in sarcoma. Possible future clinical applications include
      the use of miRNA pathways as therapeutic targets or miRNA expression profiling as
      a means of patient selection. The involvement miRNAs will undoubtedly contribute
      to the advancement of future targeted therapeutic interventions in sarcoma, and
      further establishment of appropriate delivery systems is vital for their use in
      clinical settings.

PMID- 26318098
TI  - Quantitative STEM normalisation: The importance of the electron flux.
AB  - Annular dark-field (ADF) scanning transmission electron microscopy (STEM) has
      become widely used in quantitative studies based on the opportunity to directly
      compare experimental and simulated images. This comparison merely requires the
      experimental data to be normalised and expressed in units of 'fractional beam
      current'. However, inhomogeneities in the response of electron detectors can
      complicate this normalisation. The quantification procedure becomes both
      experiment and instrument specific, requiring new simulations for the particular
      response of each instrument's detector, and for every camera-length used. This
      not only impedes the comparison between different instruments and research
      groups, but can also be computationally very time consuming. Furthermore, not all
      image simulation methods allow for the inclusion of an inhomogeneous detector
      response. In this work, we propose an alternative method for normalising
      experimental data in order to compare these with simulations that consider a
      homogeneous detector response. To achieve this, we determine the electron flux
      distribution reaching the detector by means of a camera-length series or a so
      called atomic column cross-section averaged convergent beam electron diffraction
      (XSACBED) pattern. The result is then used to determine the relative weighting of
      the detector response. Here we show that the results obtained by this new
      electron flux weighted (EFW) method are comparable to the currently used method,
      while considerably simplifying the needed simulation libraries. The proposed
      method also allows one to obtain a metric that describes the quality of the
      detector response in comparison with the 'ideal' detector response. 

PMID- 26318099
TI  - Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of
      2,5-dimethoxy-substituted phenethylamines (2C drugs).
AB  - BACKGROUND: N-2-methoxybenzyl-phenethylamines (NBOMe drugs) are newly used
      psychoactive substances with poorly defined pharmacological properties. The aim
      of the present study was to characterize the receptor binding profiles of a
      series of NBOMe drugs compared with their 2,5-dimethoxy-phenethylamine analogs
      (2C drugs) and lysergic acid diethylamide (LSD) in vitro. METHODS: We
      investigated the binding affinities of 2C drugs (2C-B, 2C-C, 2C-D, 2C-E, 2C-H, 2C
      I, 2C-N, 2C-P, 2C-T-2, 2C-T-4, 2C-T-7, and mescaline), their NBOMe analogs, and
      LSD at monoamine receptors and determined functional 5-hydroxytryptamine-2A (5
      HT2A) and 5-HT2B receptor activation. Binding at and the inhibition of monoamine
      uptake transporters were also determined. Human cells that were transfected with
      the respective human receptors or transporters were used (with the exception of
      trace amine-associated receptor-1 [TAAR1], in which rat/mouse receptors were
      used). RESULTS: All of the compounds potently interacted with serotonergic 5
      HT2A, 5-HT2B, 5-HT2C receptors and rat TAAR1 (most Ki and EC50: <1 MUM). The N-2
      methoxybenzyl substitution of 2C drugs increased the binding affinity at
      serotonergic 5-HT2A, 5-HT2C, adrenergic alpha1, dopaminergic D1-3, and
      histaminergic H1 receptors and monoamine transporters but reduced binding to 5
      HT1A receptors and TAAR1. As a result, NBOMe drugs were very potent 5-HT2A
      receptor agonists (EC50: 0.04-0.5 MUM) with high 5-HT2A/5-HT1A selectivity and
      affinity for adrenergic alpha1 receptors (Ki: 0.3-0.9 MUM) and TAAR1 (Ki: 0.06
      2.2 MUM), similar to LSD, but not dopaminergic D1-3 receptors (most Ki:>1 MUM),
      unlike LSD. CONCLUSION: The binding profile of NBOMe drugs predicts strong
      hallucinogenic effects, similar to LSD, but possibly more stimulant properties
      because of alpha1 receptor interactions.

PMID- 26318100
TI  - GABAergic control of the activity of the central nucleus of the amygdala in low-
      and high-anxiety rats.
AB  - The aim of this study was to examine the role of GABAergic neurotransmission in
      amygdala nuclei in low- (LR) and high-anxiety (HR) rats after repeated
      corticosterone administration and acute injection of the benzodiazepine
      midazolam. The animals were divided into LR and HR groups based on the duration
      of their conditioned freezing in a contextual fear test (CFT). Repeated daily
      administration of corticosterone (20 mg/kg s.c.) for 21 injections increased
      anxiety-like behavior in the open field and reduced body weight in both the LR
      and HR groups. These effects of corticosterone administration were more
      pronounced in the HR group. Moreover, in the HR group, chronic corticosterone
      administration increased the duration of freezing in the CFT test compared with
      the appropriate control group and treated LR rats. The behavioral effects in HR
      rats were accompanied by an increase in the expression of c-Fos in the lateral
      (LA) and central (CeA) nuclei of the amygdala and by a decrease in GABA-A alpha-2
      subunit density in the CeA. Acute midazolam administration significantly
      attenuated the neophobia and conditioned fear responses, decreased c-Fos
      expression in the LA and CeA, and increased alpha-2 subunit density in the CeA
      only in the HR group. These studies have shown that HR rats are more susceptible
      to the anxiogenic effects of chronic corticosterone administration, which are
      associated with the attenuation of GABAergic control over the amygdala output
      that controls emotional responses. The current data may increase understanding of
      the neurobiological mechanisms responsible for individual differences in the
      psychopathological processes induced by repeated administration of high doses of
      glucocorticoids or by elevated levels of these hormones, which are associated
      with chronic stress and affective pathology. 

PMID- 26318101
TI  - The beta3 subunit of the nicotinic acetylcholine receptor: Modulation of gene
      expression and nicotine consumption.
AB  - Genetic factors explain approximately half of the variance in smoking behaviors,
      but the molecular mechanism by which genetic variation influences behavior is
      poorly understood. SNPs in the putative promoter region of CHRNB3, the gene that
      encodes the beta3 subunit of the nicotinic acetylcholine receptor (nAChR), have
      been repeatedly associated with nicotine behaviors. In this work we sought to
      identify putative function of three SNPs in the promoter region of CHRNB3 on in
      vitro gene expression. Additionally, we used beta3 null mutant mice as a model of
      reduced gene expression to assess the effects on nicotine behaviors. The effect
      of rs13277254, rs6474413, and rs4950 on reporter gene expression was examined
      using a luciferase reporter assay. A major and minor parent haplotype served as
      the background on which alleles at the three SNPs were flipped onto different
      backgrounds (e.g. minor allele on major haplotype background). Constructs were
      tested in three human cell lines: BE(2)-C, SH-SY5Y and HEK293T. In all cell types
      the major haplotype led to greater reporter gene expression compared to the minor
      haplotype, and results indicate that this effect is driven by rs6474413.
      Moreover, mice lacking the beta3 subunit showed reduced voluntary nicotine
      consumption compared that of wildtype animals. These data provide evidence that
      the protective genetic variant at rs6474413 identified in human genetic studies
      reduces gene expression and that decreased beta3 gene expression in mice reduces
      nicotine intake. This work contributes to our understanding of the molecular
      mechanisms that contribute to the human genetic associations of tobacco
      behaviors. 

PMID- 26318103
TI  - Occurrence of Natural Contaminants of Emerging Concern in the Douro River
      Estuary, Portugal.
AB  - Many studies demonstrated the presence of diverse environmental contaminants in
      the Douro River estuary, such as natural and synthetic estrogens,
      pharmaceuticals, industrial compounds and pesticides. This estuary is located
      between two densely populated cities and is highly impacted due to anthropogenic
      activities, such as industry and agriculture. Although the presence of mycotoxins
      and phytoestrogens, such as lignans and coumestrans, in the aquatic environment
      is reported by some authors, their occurrence in Portuguese waters was not
      investigated yet. To evaluate the presence of phytoestrogens, phytosterols and
      mycotoxins in Douro River estuary, water samples were collected seasonally at
      nine sampling points, preconcentrated by solid phase extraction and analysed by
      gas chromatography mass spectrometry. Local flora was collected on the riverside,
      in the same sampling points, for identification and evaluation of the possible
      relation to the presence of phytoestrogens and/or phytosterols in the estuarine
      water. Results showed the ubiquitous presence of mycotoxins, namely
      deoxynivalenol up to 373.5 ng L(-1). Both phytoestrogens and phytosterols showed
      a possible seasonal fluctuation, which is in accordance to the life cycle of the
      local flora and agricultural practices. Physicochemical parameters were also
      determined for water quality evaluation. This study revealed for the first time
      the presence of mycotoxins and lignans in estuarine waters from Portugal, and
      highlights the need to consider natural contaminants in future monitoring
      programs. 

PMID- 26318102
TI  - Investigation of the role of betaarrestin2 in kappa opioid receptor modulation in
      a mouse model of pruritus.
AB  - The kappa opioid receptor (KOR) is involved in mediating pruritus; agonists
      targeting this receptor have been used to treat chronic intractable itch.
      Conversely, antagonists induce an itch response at the site of injection. As a G
      protein-coupled receptor (GPCR), the KOR has potential for signaling via G
      proteins and betaarrestins, however, it is not clear which of these pathways are
      involved in the KOR modulation of itch. In this study asked whether the actions
      of KOR in pruritus involve betaarrestins by using betaarrestin2 knockout
      (betaarr2-KO) mice as well as a recently described biased KOR agonist that biases
      receptor signaling toward G protein pathways over betaarrestin2 recruitment. We
      find that the KOR antagonists nor-binaltorphimine (NorBNI) and 5'
      guanidinonaltrindole (5'GNTI) induce acute pruritus in C57BL/6J mice, with
      reduced effects in KOR-KO mice. betaArr2-KO mice display less of a response to
      KOR antagonist-induced itch compared to wild types, however no genotype
      differences are observed from chloroquine phosphate (CP)-induced itch, suggesting
      that the antagonists may utilize a KOR-betaarrestin2 dependent mechanism. The KOR
      agonist U50,488H was equally effective in both WT and betaarr2-KO mice in
      suppressing CP-induced itch. Furthermore, the G protein biased agonist,
      Isoquinolinone 2.1 was as effective as U50,488H in suppressing the itch response
      induced by KOR antagonist NorBNI or CP in C57BL/6J mice. Together these data
      suggest that the antipruritic effects of KOR agonists may not require
      betaarrestins. 

PMID- 26318105
TI  - Can the AHA-ACC ASCVD risk score be applied outside the United States in Korea?

PMID- 26318104
TI  - Favorable effect of optimal lipid-lowering therapy on neointimal tissue
      characteristics after drug-eluting stent implantation: qualitative optical
      coherence tomographic analysis.
AB  - OBJECTIVE: Serial follow-up optical coherence tomography (OCT) was used to
      evaluate the effect of optimal lipid-lowering therapy on qualitative changes in
      neointimal tissue characteristics after drug-eluting stent (DES) implantation.
      METHODS: DES-treated patients (n = 218) who received statin therapy were examined
      with serial follow-up OCT. First and second follow-up OCT evaluations were
      performed approximately 6 and 18 months after the index procedure, respectively.
      Patients were divided into two groups, based on the level of low-density
      lipoprotein-cholesterol (LDL-C), which was measured at the second follow-up. The
      optimal lipid-lowering group (n = 121) had an LDL-C reduction of >=50% or an LDL
      C level <=70 mg/dL, and the conventional group (n = 97). Neointimal
      characteristics were qualitatively categorized as homogeneous or non-homogeneous
      patterns using OCT. The non-homogeneous group included heterogeneous, layered, or
      neoatherosclerosis patterns. Qualitative changes in neointimal tissue
      characteristics between the first and second follow-up OCT examinations were
      assessed. RESULTS: Between the first and second follow-up OCT procedures, the
      neointimal cross-sectional area increased more substantially in the conventional
      group (0.4 mm(2) vs. 0.2 mm(2) in the optimal lipid-lowering group, p = 0.01).
      The neointimal pattern changed from homogeneous to non-homogeneous less often in
      the optimal lipid-lowering group (1.3%, 1/77, p < 0.001) than in the conventional
      group (15.3%, 11/72, p = 0.44). Optimal LDL-C reduction was an independent
      predictor for the prevention of neointimal pattern change from homogeneous to non
      homogeneous (odds ratio: 0.05, 95% confidence interval: 0.01~0.46, p = 0.008).
      CONCLUSION: Our findings suggest that an intensive reduction in LDL-C levels can
      prevent non-homogeneous changes in the neointima and increases in neointimal
      cross-sectional area compared with conventional LDL-C controls.

PMID- 26318106
TI  - A novel small molecule TLR4 antagonist (IAXO-102) negatively regulates non
      hematopoietic toll like receptor 4 signalling and inhibits aortic aneurysms
      development.
AB  - OBJECTIVES: The toll-like receptors (TLRs), including TLR4, have been shown to
      play a crucial role in vascular inflammatory diseases, such as atherosclerosis
      and aneurysm. The main goal of this study was to determine the potential of IAXO
      102 (Innaxon, Tewkesbury), a novel small molecule TLR4 antagonist, to modulate
      non-hematopoietic TLR4 proinflammatory signalling and inhibit experimental
      abdominal aortic aneurysm (AAA) development. METHODS: Human umbilical vein
      endothelial cells (HUVEC) and Angiotensin II-induced experimental AAA development
      were our in vitro and in vivo models respectively. Western blotting, antibody
      array and ELISA approaches were used to explore the effect of IAXO-102 on TLR4
      functional activity on two levels: modulation of TLR4-induced mitogen activated
      protein kinases (MAPK) and p65 NF-kB phosphorylation and expression of TLR4
      dependent proinflammatory proteins. RESULTS: Following activation of TLR4, in
      vitro/in vivo data revealed that IAXO-102 inhibited MAPK and p65 NF-kB
      phosphorylation associated with down regulation of the expression of TLR4 and
      TLR4 dependent proinflammatory proteins. Furthermore, IAXO-102 decreased
      Angiotensin II-induced aortic expansion, rupture and incidence of AAA.
      CONCLUSIONS: These results demonstrate the ability of IAXO-102 to negatively
      regulate TLR4 signalling and to inhibit experimental AAA development, suggesting
      the potential therapeutic use of this TLR4 antagonist for pharmacological
      intervention of AAA.

PMID- 26318107
TI  - SASH1, a new potential link between smoking and atherosclerosis.
AB  - OBJECTIVE: We have previously reported that SASH1 expression is increased in
      circulating human monocytes from smokers and was positively correlated with the
      number of carotid atherosclerotic plaques. The aim of this study was to further
      validate the link between smoking, SASH1 and atherosclerosis within the vascular
      wall and to assess the impact of SASH1 expression on endothelial cell functions.
      METHOD: Human carotids with atherosclerotic plaques were obtained from 58
      patients (45 of them with known smoking status: smoker, non-smoker, ex-smokers),
      and were processed for gene expression analyses and immunostaining. To
      investigate its function, SASH1 was silenced in human aortic endothelial cells
      (HAECs) using two different siRNA and subcellular localization of SASH1 was
      determined by immunostaining and subcellular fractionation. Subsequently the
      transcriptomic analyses and functional experiments (wound healing, WST-1
      proliferation or Matrigel assays) were performed to characterize SASH1 function.
      RESULTS: SASH1 was expressed in human vascular cells (HAECs, smooth muscle cells)
      and in monocytes/macrophages. Its tissue expression was significantly higher in
      the atherosclerotic carotids of smokers compared to non-smokers (p < 0.01). In
      HAECs, SASH1 was expressed mostly in the cytoplasm and SASH1 knockdown resulted
      in an increased cell migration, proliferation and angiogenesis. Transcriptomic
      and pathway analyses showed that SASH1 silencing results in a decreased CYP1A1
      expression possibly through the inhibition of TP53 activity. CONCLUSION: We
      showed that SASH1 expression is increased in atherosclerotic carotids in smokers
      and its silencing affects endothelial angiogenic functions; therefore we provide
      a potential link between smoking and atherosclerosis through SASH1 expression.

PMID- 26318108
TI  - Increased plasma dipeptidyl peptidase-4 activities are associated with high
      prevalence of subclinical atherosclerosis in Chinese patients with newly
      diagnosed type 2 diabetes: a cross-sectional study.
AB  - OBJECTIVE: Hyperglycemia, insulin resistance, dislipidemia, oxidative stress and
      inflammation are well-documented risk factors for subclinical atherosclerosis.
      Dipeptidyl peptidase-4(DPP4) is a newly identified adipokine related to these
      risk factors. Hence, we aimed to investigate the association between plasma DPP4
      activities and subclinical atherosclerosis in type 2 diabetes. METHODS: A total
      of 985 newly diagnosed type 2 diabetic subjects were studied. Plasma DPP4
      activity, mannose 6-phosphate receptor (M6P-R), oxidative stress parameters,
      inflammatory markers and common carotid artery Intima-Media Thickness (c-IMT)
      were measured in all participants. RESULTS: Participants in the highest quartile
      of DPP4 activity had higher HbA1c, homeostatic model assessment of insulin
      resistance(HOMA-IR), triglyceride, low-density lipoprotein cholesterol(LDL-C),
      oxidized LDL, nitrotyrosine, 8-iso-PGF2a, interleukin-6 (IL-6), high-sensitivity
      C-reactive protein (hs-CRP), M6P-R, c-IMT compared with participants in the
      lowest quartile (all P < 0.001). DPP4 activities were associated positively with
      HbA1c, HOMA-IR, triglyceride, LDL-C, oxidized LDL, nitrotyrosine, 8-iso-PGF2a, IL
      6, hs-CRP, M6P-R and c-IMT (all P < 0.05). The ORs for insulin resistance,
      dislipidemia, oxidative stress and inflammation were higher with increasing DPP4
      quartiles (P < 0.001 for trend). In the highest DPP4 quartile, subclinical
      atherosclerosis risk was significantly higher (OR 4.97; 95% CI 3.03-8.17) than in
      the lowest quartile. This association remained strong (2.17; 1.21-3.89) after
      further controlling for HbA1c, HOMA-IR, triglyceride, oxidized LDL,
      nitrotyrosine, and IL-6. CONCLUSIONS: This study shows that increased DPP4
      activities are positively and independently associated with subclinical
      atherosclerosis in type 2 diabetes. Our findings suggest of potential role of
      DPP4 in the pathogenesis of subclinical atherosclerosis and in the prevention and
      management of this disease.

PMID- 26318112
TI  - Improving point correspondence in cephalograms by using a two-stage rectified
      point transform.
AB  - BACKGROUND: An improved point correspondence method was developed for
      automatically detecting two-dimensional cephalometric landmarks. The proposed
      method uses a two-stage rectified point transform: the global correspondence of
      interest points between two images and the local correspondence of landmarks.
      METHOD: In the first stage, point-to-point matching pairs were established using
      local corner point features. The matched points on an input image were treated as
      a set of transformations, with varying directions and magnitudes, from the
      template image. Similarity of the transformation vectors was achieved through
      rectification to exclude vectors that deviated widely from the statistical mean.
      Rectification attempted to remove noise and irrelevant matched points. In the
      second stage, the point correspondences were fine-tuned within the regional
      centers of the landmarks, which were classified into three categories-corners,
      edges, and structural points-and each category was fine-tuned using a different
      strategy. Correspondence was performed by evaluating the shortest Euclidean
      distance between the point descriptors of the template and test images. RESULTS:
      The correspondence results of 20 orthodontic landmarks were compared with those
      identified by dental professionals on 80 digital cephalograms collected from a
      dental clinic. The proposed method detected both hard and soft tissue landmarks
      with mean error distances of 1.63mm, compared with the 2-mm standard reported by
      previous studies. CONCLUSIONS: This study enhanced the point correspondence
      technique for cephalometric landmarking. Using the proposed method, users can
      preferentially and flexibly add and remove landmarks on a template before
      correspondence without intensive image pretraining.

PMID- 26318109
TI  - Elevated baseline plasma IL-8 levels are an independent predictor of long-term
      all-cause mortality in patients with acute coronary syndrome.
AB  - OBJECTIVES: To investigate the long-term prognostic significance of baseline
      plasma IL-8 levels in a group of well-characterized male patients presenting with
      acute coronary syndrome. BACKGROUND: IL-8 is a cytokine that has been implicated
      in the pathogenesis of atherosclerosis and acute coronary syndrome. Elevated
      plasma levels have been reported in patients with acute coronary syndrome.
      METHODS: Baseline plasma IL-8 levels were measured in 180 male patients with
      acute coronary syndrome who were referred for coronary angiography and followed
      prospectively for the development of all-cause mortality for 5 years. RESULTS: In
      a multivariate model that included a wide variety of baseline clinical,
      laboratory and angiographic parameters in the selection process, baseline plasma
      IL-8 levels (analyzed as a continuous variable) emerged as a significant
      predictor of all-cause mortality at 5 years (HR, 1.43; 95% CI, 1.08-1.88; p =
      0.0123). Furthermore, in 3 additional multivariate models that also included in
      the selection process a number of contemporary biomarkers with established
      prognostic efficacy in ACS (i.e., NT-proBNP, hs-CRP, hemoglobin and RDW), IL-8
      remained an independent predictor of all-cause mortality at 5 years. CONCLUSION:
      Elevated baseline plasma levels of IL-8 are associated with an increased risk of
      long-term all-cause mortality in patients with acute coronary syndrome.
      Furthermore, this association is independent of a variety of clinical, laboratory
      and angiographic variables, including contemporary biomarkers with established
      prognostic efficacy in acute coronary syndrome.

PMID- 26318110
TI  - Which women with breast cancer do, and do not, undergo receptor status testing? A
      population-based study.
AB  - INTRODUCTION: Receptor status determines of breast cancer treatment and
      prognosis. In a population-based study, we investigated predictors of receptor
      test receipt. MATERIALS AND METHODS: Invasive breast cancers diagnosed 2006-2008
      were abstracted from the National Cancer Registry Ireland. Modified Poisson
      regression with robust error variance was used to identify socio-demographic,
      health service and clinical predictors of not undergoing ER, PR or HER2 testing.
      RESULTS: 7619 breast cancers were included. 7% were not tested for any receptor.
      92%, 80% and 86% had oestrogen (ER), progesterone (PR) and human epidermal growth
      factor 2 (HER2) tests, respectively; 73% were tested for all three. For all three
      tests, unmarried women were significantly less likely to be tested than married
      women. Current smokers significantly more often had ER and PR tests. Women
      treated in a high-volume hospital significantly more often had ER and HER2 tests.
      CONCLUSION: After adjusting for clinical factors, socio-demographic and service
      related factors significantly predicted receptor test receipt. Some factors
      deserve further investigation, especially marital status. In the interests of
      equity, the reasons underlying these associations should be further investigated.

PMID- 26318113
TI  - Automated segmentation of geographic atrophy of the retinal epithelium via random
      forests in AREDS color fundus images.
AB  - BACKGROUND: Age-related macular degeneration (AMD), left untreated, is the
      leading cause of vision loss in people older than 55. Severe central vision loss
      occurs in the advanced stage of the disease, characterized by either the in
      growth of choroidal neovascularization (CNV), termed the "wet" form, or by
      geographic atrophy (GA) of the retinal pigment epithelium (RPE) involving the
      center of the macula, termed the "dry" form. Tracking the change in GA area over
      time is important since it allows for the characterization of the effectiveness
      of GA treatments. Tracking GA evolution can be achieved by physicians performing
      manual delineation of GA area on retinal fundus images. However, manual GA
      delineation is time-consuming and subject to inter-and intra-observer
      variability. METHODS: We have developed a fully automated GA segmentation
      algorithm in color fundus images that uses a supervised machine learning approach
      employing a random forest classifier. This algorithm is developed and tested
      using a dataset of images from the NIH-sponsored Age Related Eye Disease Study
      (AREDS). GA segmentation output was compared against a manual delineation by a
      retina specialist. RESULTS: Using 143 color fundus images from 55 different
      patient eyes, our algorithm achieved PPV of 0.82+/-0.19, and NPV of 0:95+/-0.07.
      DISCUSSION: This is the first study, to our knowledge, applying machine learning
      methods to GA segmentation on color fundus images and using AREDS imagery for
      testing. These preliminary results show promising evidence that machine learning
      methods may have utility in automated characterization of GA from color fundus
      images.

PMID- 26318114
TI  - Non-uniform central airways ventilation model based on vascular segmentation.
AB  - Improvements in the understanding of the physiology of the central airways
      require an appropriate representation of the non-uniform ventilation at its
      terminal branches. This paper proposes a new technique for estimating the non
      uniform ventilation at the terminal branches by modelling the volume change of
      their distal peripheral airways, based on vascular segmentation. The vascular
      tree is used for sectioning the dynamic CT-based 3D volume of the lung at 11 time
      points over the breathing cycle of a research animal. Based on the mechanical
      coupling between the vascular tree and the remaining lung tissues, the volume
      change of each individual lung segment over the breathing cycle was used to
      estimate the non-uniform ventilation of its associated terminal branch. The 3D
      lung sectioning technique was validated on an airway cast model of the same
      animal pruned to represent the truncated dynamic CT based airway geometry. The
      results showed that the 3D lung sectioning technique was able to estimate the
      volume of the missing peripheral airways within a tolerance of 2%. In addition,
      the time-varying non-uniform ventilation distribution predicted by the proposed
      sectioning technique was validated against CT measurements of lobar ventilation
      and showed good agreement. This significant modelling advance can be used to
      estimate subject-specific non-uniform boundary conditions to obtain subject
      specific numerical models of the central airway flow. 

PMID- 26318115
TI  - Polymorphisms of pesticide-metabolizing genes in children living in intensive
      farming communities.
AB  - Polymorphisms in genes encoding xenobiotic-metabolizing enzymes (XME) are
      important parameters accounting for the wide inter-individual variability to
      environmental exposures. Paraoxonase-1 (PON1), butyrylcholinesterase (BChE) and
      Cytochrome-P450 constitute major classes of XME involved in the detoxification of
      pesticide chemicals, in particular organophosphates. This study explored the
      allelic frequency, linkage disequilibrium and haplotype analysis of ten common
      polymorphic variants of seven key genes involved in organophosphate metabolism
      (BCHE-K, BCHE-A, PON1 Q192R, PON1 L55M, PON1 -108C/T, CYP2C19 G681A, CYP2D6
      G1846A, CYP3AP1 -44G/A, GSTM1*0 and GSTT1*0) in a children population living near
      an intensive agriculture area in Spain. It was hypothesized that individuals with
      unfavorable combinations of gene variants will be more susceptible to adverse
      effects from organophosphate exposure. Genomic DNA from 496 healthy children was
      isolated and amplified by PCR. Hydrolysis probes were used for the detection of
      eight specific SNPs and two copy number variants (CNVs) by using TaqMan(r) Assay
      based real-time PCR. Frequencies of SNPs and CNVs in the target genes were in
      Hardy-Weinberg equilibrium and broadly consistent with European populations.
      Linkage disequilibrium was found between the three PON1 genetic polymorphisms
      studied and between BCHE-K and BCHE-A. The adverse genotype combination (unusual
      BCHE variants, PON1 55MM/-108TT and null genotype for both GSTM1 and GSTT1)
      potentially conferring a greater genetic risk from exposure to organophosphates
      was observed in 0.2% of our study population. This information allows broadening
      our knowledge about differential susceptibility toward environmental toxicants
      and may be helpful for further research to understand the inter-individual
      toxicokinetic variability in response to organophosphate pesticides exposure.

PMID- 26318116
TI  - Antioxidant responses of triangle sail mussel Hyriopsis cumingii exposed to
      harmful algae Microcystis aeruginosa and hypoxia.
AB  - Bloom forming algae and hypoxia are considered to be two main co-occurred
      stressors associated with eutrophication. The aim of this study was to evaluate
      the interactive effects of harmful algae Microcystis aeruginosa and hypoxia on an
      ecologically important mussel species inhabiting lakes and reservoirs, the
      triangle sail mussel Hyriopsis cumingii, which is generally considered as a bio
      management tool for eutrophication. A set of antioxidant enzymes involved in
      immune defence mechanisms and detoxification processes, i.e. glutathione-S
      transferases (GST), glutathione (GSH), superoxide dismutase (SOD), catalase
      (CAT), glutathione peroxidase (GPX), lysozyme (LZM) in mussel haemolymph were
      analyzed during 14days exposure along with 7days depuration duration period. GST,
      GSH, SOD, GPX and LZM were elevated by toxic M. aeruginosa exposure, while CAT
      activities were inhibited by such exposure. Hypoxia influenced the immune
      mechanisms through the activation of GSH and GPX, and the inhibition of SOD, CAT,
      and LZM activities. Meanwhile, some interactive effects of M. aeruginosa, hypoxia
      and time were observed. Independently of the presence or absence of hypoxia,
      toxic algal exposure generally increased the five tested enzyme activities of
      haemolymph, except CAT. Although half of microcystin could be eliminated after
      7days depuration, toxic M. aeruginosa or hypoxia exposure history showed some
      latent effects on most parameters. These results revealed that toxic algae play
      an important role on haemolymph parameters alterations and its toxic effects
      could be affected by hypoxia. Although the microcystin depuration rate of H.
      cumingii is quick, toxic M. aeruginosa and/or hypoxia exposure history influenced
      its immunological mechanism recovery.

PMID- 26318117
TI  - The usefulness of a sediment bioassay with the gastropod Nassarius reticulatus in
      tributyltin monitoring programs.
AB  - Despite the use of tributyltin (TBT) had been banned worldwide in 2008 there is
      still evidence of its deleterious presence in environment. We evaluate the
      usefulness of a 28days sediment bioassay with Nassarius reticulatus females to
      monitor TBT pollution, using imposex as endpoint. In addition, butyltins were
      determined in sediments and tissues, and, whenever posible, imposex was assessed
      in native N. reticulatus at the same sites where sediments were sampled. In the
      bioassay, a significant increase in imposex parameters was obtained with three
      sediments (Vi2, Vi3, and Vi4). No correlation was found between this and TBT
      concentrations in sediment although good correlations were obtained for TBT in
      tissues, putting in evidence TBT bioavailability in sediment. A significant
      decrease in imposex from 2008 to 2013 in native snails was only observed at sites
      that did not cause any effect in the bioassay. In contrast, imposex levels in
      2013 were kept as high as 2008 in one of the sites where a significant imposex
      increase in the bioassay was observed. The bioassay proves thus to be a practical
      and ecological relevant tool, as: (i) it can be conducted in sites with no native
      populations of snails, (ii) it provides early identification of polluted sites,
      anticipating future imposex levels or early identification of recovering, and
      (iii) it yields information on the bioavailable fraction of the TBT in the
      sediment. Therefore, this tool can be of extreme usefulness under the scope of
      recent European legislative frameworks.

PMID- 26318118
TI  - Toxicity of Vertimec(r) 18 EC (active ingredient abamectin) to the neotropical
      cladoceran Ceriodaphnia silvestrii.
AB  - The aim of the present study was to evaluate the toxicity of abamectin to the
      neotropical cladoceran Ceriodaphnia silvestrii. To this end, acute and chronic
      bioassays were conducted with the commercial formulation Vertimec(r) 18 EC. In
      addition, the toxicity of water samples taken from a microcosm experiment
      evaluating the effects of a single application (144MUga.i./L) and two
      applications (2*36MUga.i./L) of Vertimec(r) 18 EC, in the presence or absence of
      a tadpole species (Lithobates catesbeianus), was also assessed. The acute LC50
      48h for immobilization was 1.47MUga.i./L and chronic NOEC-8d for survival and
      fertility (number of neonates per female) were 169 and 84nga.i./L, respectively.
      Irrespective of the presence of tadpoles, water samples from the microcosms
      applied with the single concentration of 144MUga.i./L remained toxic until the
      end of the experiment, even when samples were diluted 32 times with culture
      medium. Water in the repeated pesticide treatment showed a similar toxic response
      after both applications. Toxicity of water samples from the microcosms was lower
      than that expected based on the generated LC50 values, which is explained by a
      potential reduced bioavailability of the test compound resulting from absorbance
      to organic material. Potential side-effects on C. silvestrii related with the use
      of Vertimec(r) 18 EC in Brazil and the suitability of this species for tropical
      toxicity testing are discussed.

PMID- 26318119
TI  - Legacy and emerging halogenated organic pollutants in marine organisms from the
      Pearl River Estuary, South China.
AB  - A suite of legacy and emerging halogenated organic pollutants (HOPs) were
      measured in marine organisms (coastal fish and invertebrates) from the Pearl
      River Estuary, South China, to investigate the current contamination status after
      the Stockholm Convention was implemented in China.
      Dichlorodiphenyltrichloroethane and its metabolites (DDTs), polychlorinated
      biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs) were detected in all
      samples at concentrations of 54-1500, 16-700, and 0.56-59ng/g lipid weight,
      respectively. Dechlorane Plus (DP), decabromodiphenyl ethane (DBDPE), 2,3,5,6
      tetrabromo-p-xylene (pTBX), and pentabromotoluene (PBT) were also found at
      concentrations of ND (non-detectable) to 37ng/g lipid weight. The concentrations
      of these investigated contaminants in the present study were at moderate levels,
      as compared with those reported in other regions. Significant interspecies
      differences were found in the levels of DDTs, PCBs, PBDEs and the alternative
      halogenated flame retardants (AHFRs). DDTs were the predominant HOPs in those
      species and represented >50% of the total HOPs, followed by PCBs, PBDEs, and
      AHFRs. The total estimated daily intakes (EDIs) of DDTs, PCBs, PBDEs, and AHFRs
      were 28, 12, 1.0, and 0.18 (ng/kg)/d, respectively, via seafood consumption.
      These concentrations are not expected to pose health risks to humans.

PMID- 26318120
TI  - Stand Up and Make a Difference!

PMID- 26318121
TI  - High-Fat Diet Alters Serum Fatty Acid Profiles in Obesity Prone Rats:
      Implications for In Vitro Studies.
AB  - High-fat diets (HFD) are commonly used in rodents to induce obesity, increase
      serum fatty acids and induce lipotoxicity in various organs. In vitro studies
      commonly utilize individual free fatty acids (FFA) to study lipid exposure in an
      effort to model what is occurring in vivo; however, these approaches are not
      physiological as tissues are exposed to multiple fatty acids in vivo. Here we
      characterize circulating lipids in obesity-prone rats fed an HFD in both fasted
      and fed states with the goal of developing physiologically relevant fatty acid
      mixtures for subsequent in vitro studies. Rats were fed an HFD (60% kcal fat) or
      a control diet (10% kcal fat) for 3 weeks; liver tissue and both portal and
      systemic blood were collected. Fatty acid profiles and absolute concentrations of
      triglycerides (TAG) and FFA in the serum and TAG, diacylglycerol (DAG) and
      phospholipids in the liver were measured. Surprisingly, both systemic and portal
      serum TAG were ~40% lower in HFD-fed compared to controls. Overall, compared to
      the control diet, HFD feeding consistently induced an increase in the proportion
      of circulating polyunsaturated fatty acids (PUFA) with a concomitant decline in
      monounsaturated fatty acids (MUFA) and saturated fatty acids (SFA) in both serum
      TAG and FFA. The elevations of PUFA were mostly attributed to increases in n-6
      PUFA, linoleic acid and arachidonic acid. In conclusion, fatty acid mixtures
      enriched with linoleic and arachidonic acid in addition to SFA and MUFA should be
      utilized for in vitro studies attempting to model lipid exposures that occur
      during in vivo HFD conditions.

PMID- 26318122
TI  - Adapting existing natural language processing resources for cardiovascular risk
      factors identification in clinical notes.
AB  - The 2014 i2b2 natural language processing shared task focused on identifying
      cardiovascular risk factors such as high blood pressure, high cholesterol levels,
      obesity and smoking status among other factors found in health records of
      diabetic patients. In addition, the task involved detecting medications, and time
      information associated with the extracted data. This paper presents the
      development and evaluation of a natural language processing (NLP) application
      conceived for this i2b2 shared task. For increased efficiency, the application
      main components were adapted from two existing NLP tools implemented in the
      Apache UIMA framework: Textractor (for dictionary-based lookup) and cTAKES (for
      preprocessing and smoking status detection). The application achieved a final
      (micro-averaged) F1-measure of 87.5% on the final evaluation test set. Our
      attempt was mostly based on existing tools adapted with minimal changes and
      allowed for satisfying performance with limited development efforts. 

PMID- 26318123
TI  - miR-142-3p is a Potential Therapeutic Target for Sensory Function Recovery of
      Spinal Cord Injury.
AB  - Spinal cord injury (SCI), which is a leading cause of disability in modern
      society, commonly results from trauma. It has been reported that application of
      sciatic nerve conditioning injury plays a positive role in repairing the injury
      of the ascending spinal sensory pathway in laboratory animals. Because of the
      complexity of SCI and related ethics challenges, sciatic nerve conditioning
      injury cannot be applied in clinical therapy. Accordingly, it is extremely
      important to study its mechanism and develop replacement therapy. Based on
      empirical study and clinical trials, this article suggests that miR-142-3p is the
      key therapeutic target for repairing sensory function, based on the following
      evidence. Firstly, studies have reported that endogenous cAMP is the upstream
      regulator of 3 signal pathways that are partially involved in the mechanisms of
      sciatic nerve conditioning injury, promoting neurite growth. The regulated miR
      142-3p can induce cAMP elevation via adenylyl cyclase 9 (AC9), which is abundant
      in dorsal root ganglia (DRG). Secondly, compared with gene expression regulation
      in the injured spinal cord, inhibition of microRNA (miRNA) in DRG is less likely
      to cause trauma and infection. Thirdly, evidence of miRNAs as biomarkers and
      therapeutic targets in many diseases has been reported. In this article we
      suggest, for the first time, imitating sciatic nerve conditioning injury, thereby
      enhancing central regeneration of primary sensory neurons via interfering with
      the congenerous upstream regulator AC9 of the 3 above-mentioned signal pathways.
      We hope to provide a new clinical treatment strategy for the recovery of sensory
      function in SCI patients. 

PMID- 26318124
TI  - Efficient ligase 3-dependent microhomology-mediated end joining repair of DNA
      double-strand breaks in zebrafish embryos.
AB  - DNA double-strand break (DSB) repair is of considerable importance for genomic
      integrity. Homologous recombination (HR) and non-homologous end joining (NHEJ)
      are considered as two major mechanistically distinct pathways involved in
      repairing DSBs. In recent years, another DSB repair pathway, namely,
      microhomology-mediated end joining (MMEJ), has received increasing attention.
      MMEJ is generally believed to utilize an alternative mechanism to repair DSBs
      when NHEJ and other mechanisms fail. In this study, we utilized zebrafish as an
      in vivo model to study DSB repair and demonstrated that efficient MMEJ repair
      occurred in the zebrafish genome when DSBs were induced using TALEN
      (transcription activator-like effector nuclease) or CRISPR (clustered regularly
      interspaced short palindromic repeats)/Cas9 technologies. The wide existence of
      MMEJ repair events in zebrafish embryos was further demonstrated via the
      injection of several in vitro-designed exogenous MMEJ reporters. Interestingly,
      the inhibition of endogenous ligase 4 activity significantly increased MMEJ
      frequency, and the inhibition of ligase 3 activity severely decreased MMEJ
      activity. These results suggest that MMEJ in zebrafish is dependent on ligase 3
      but independent of ligase 4. This study will enhance our understanding of the
      mechanisms of MMEJ in vivo and facilitate inducing desirable mutations via DSB
      induced repair. 

PMID- 26318125
TI  - A case of gastrocolic fistula secondary to adenocarcinoma of the colon.
AB  - INTRODUCTION: Gastrocolic fistula secondary to colon carcinoma is a rare entity.
      The common cause of gastrocolic fistula is different between eastern and western
      countries. Gastrocolic fistula may present many manifestations. PRESENTATION OF
      CASE: We present a case report of gastrocolic fistula in a 59-year-old male
      patient with colon adenocarcinoma, diagnosed on digestive endoscopy, CT scanning
      and barium enema. Radical en-bloc surgery was undertaken based on patient's
      symptom, the size and the nature of the tumor. DISCUSSION: The typical symptoms
      of gastrocolic fistula include abdominal pain, vomiting, diarrhea, emaciation,
      anemia, hypoaluminemia, weight loss and ascites. There are many methods to
      diagnose gastrocolic fistula, but barium enema is the most accepted way nowadays.
      CONCLUSION: It is rare for gastrocolic fistula case to be caused by colon
      adenocarcinoma, and has been rarely reported inside China. The best therapy of
      gastrocolic fistula remains radical en-bloc surgery.

PMID- 26318126
TI  - Laparoscopic resection of intra-abdominal metastasis from intracranial
      hemangiopericytoma.
AB  - INTRODUCTION: Hemangiopericytoma (HPC) is a rare mesenchymal tumor derived from
      capillary and postcapillary pericytes that often has an indolent course and
      occasionally presents with abdominal metastasis. PRESENTATION OF CASE: Twenty
      three years after the initial resection of an intracranial HPC located in the
      right frontoparietal region and left lateral ventricle, a 63-year-old man
      experienced dull abdominal pain and early satiety and had a palpable epigastric
      mass. Computed tomography indicated a suspected metastasis of HPC to the left
      upper abdomen. On laparoscopic exploration, the tumor was found in the falciform
      ligament and was excised laparoscopically per request of the patient. He had a
      fast recovery and experienced good relief of his pain and satiety. The patient
      had 2 additional metastases at his 12-month follow-up, both in the right
      retroperitoneum, and he again underwent laparoscopic resection. At his next
      annual follow-up, new metastases were identified in his liver, small-bowel
      mesentery, and peritoneal surface, prompting a trial of systemic chemotherapy.
      Because of progress of a left lower abdominal preperitoneal metastasis on follow
      up at 3 years, the patient underwent a further successful laparoscopic
      exploration. Postoperatively, systemic chemotherapy was maintained. DISCUSSION:
      We report the recurrent laparoscopic resection of peritoneal metastases of
      primary intracranial HPC with good symptom control and fast recovery. Both the
      patient and the referring physician requested a minimally invasive surgical
      approach. CONCLUSION: Laparoscopic resection is a feasible treatment strategy for
      intraperitoneal metastases and is effective in symptom palliation.

PMID- 26318127
TI  - Parapharyngeal space lipomatosis with secondary dyspnea, disphagia and disphonia.
AB  - INTRODUCTION: Parapharyngeal space tumors are a small percentage of all head and
      neck neoplasms. Due to their anatomic location, they represent a therapeutic
      challenge. To our knowledge, 11 cases of parapharyngeal lipomatous tumors have
      been reported in the literature. CASE: A 48 year old male with chief complaints
      of dyspnea, dysphagia and dysphonia was found to have a parapharyngeal space
      tumor. He was scheduled to undergo lumpectomy and neck exploration. DISCUSSION:
      Benign tumors represented 70% of all cases. Open neck surgery is considered the
      gold-standard of treatment. CONCLUSION: It is important to bear in mind the
      lipomas of the parapharyngeal space to establish an accurate diagnosis and
      implement timely, appropriate treatment in order to avoid future complications
      and reduce morbidity and mortality.

PMID- 26318128
TI  - 10 Levels thoracic no-intrumented laminectomy for huge spontaneous spinal
      subdural hematoma removal. Report of the first case and literature review.
AB  - INTRODUCTION: Spontaneous idiopathic acute spinal subdural hematoma (SSDH) is a
      rare cause of acute back pain followed by signs and symptoms of nerve root and/or
      spinal cord compression, frequently associated with coagulopathies, blood
      dyscrasias and arterio-venous malformations. Standard management includes non
      operative treatment and timely (within 24h) surgical decompression. PRESENTATION
      OF CASE: We report on the case of a huge 10 levels SSDH treated with
      decompressive thoracic no-instrumented laminectomy in a 45-year-old woman with
      good neurological recovery (from ASIA A to D). DISCUSSION: Spontaneous SSDHs
      without detectable structural lesion or anticoagulant therapy are very rare.
      Among 26 cases documented the literature harbouring SSDHs, the thoracic spine was
      found to be the preferred site, and the compression was usually extending over
      several vertebral levels. Nonoperative treatment for SSDH may be justified in
      presence of minimal neurologic deficits, otherwise, early decompressive
      laminectomy along with evacuation of hematoma are considered the treatment of
      choice in presence of major deficits. CONCLUSION: To our knowledge, the present
      case is the most extensive laminectomy for a SSDH removal never described before.
      No postoperative instability occurs in 10 levels thoracic laminectomy in case the
      articular processes are spared. When major neurological deficits are documented,
      early decompressive laminectomy with evacuation of hematoma should be considered
      the best treatment for SSDH.

PMID- 26318129
TI  - Prostate carcinoma mimicking a sphenoid wing meningioma.
AB  - INTRODUCTION: We report here on a rare case of a large, lateral sphenoid wing
      tumor with radiographic and intraoperative findings highly suggestive of
      meningioma, yet pathology was in fact consistent with metastatic prostate
      adenocarcinoma. PRESENTATION OF CASE: An 81 year-old male presented with
      expressive dysphasia, right-sided weakness and headaches. Imaging revealed a
      heterogeneously-enhancing lesion based on the left lateral sphenoid wing. The
      presumed diagnosis was strongly in favor of meningioma, and the patient underwent
      complete resection of the dural-based lesion. Final pathology confirmed the
      unexpected finding of a metastatic prostate adenocarcinoma. Although he tolerated
      surgery well, the patient was subsequently referred for palliative therapy given
      findings of widespread systemic disease. DISCUSSION: Intracranial metastases may
      involve the dura, at times presenting with rare radiographic features highly
      suggestive for meningioma, as in our case here. This makes differentiation, at
      least based on imaging, a challenge. Elderly patients presenting with
      neurological deficits secondary to a newly-diagnosed, dural-based lesion should
      thus be considered for metastasis, prompting additional imaging studies
      (including body CT, MRI or PET) to rule out a primary lesion elsewhere. In some
      cases, this may affect the overall decision to proceed with surgical resection,
      or alternatively, to proceed directly to palliative therapy (the latter decision
      made in the context of widespread metastatic disease). CONCLUSION: We conclude
      that dural-based metastatic lesions may mimic meningiomas, warranting thorough
      pre-operative work-up to exclude the possibility of metastasis. In certain cases,
      identification of widespread disease might preclude surgery and favor palliation,
      instead.

PMID- 26318130
TI  - Low-grade mucinous neoplasia in a cecal diverticulum: A case report.
AB  - INTRODUCTION: Low-grade mucinous neoplasia is an uncommon benign tumor that
      develops in the appendix. The development of mucocele disease has never been
      reported in a colonic diverticulum. We present a case developing low-grade
      mucinous neoplasia in a cecal diverticulum. PRESENTATION OF CASE: A tumor in the
      ileocecal region was found during a medical examination of a 66-year-old woman.
      Three months later, the tumor was still present and the patient developed
      abdominal pain. Laparoscopic ileocecal resection with D2 lymph node dissection
      was performed. Histopathological examination revealed a low-grade mucinous
      neoplasm in a cecal diverticulum. DISCUSSION: Colonic mucoceles reportedly
      originate from the appendix. There are no previous reports of mucocele disease in
      a colonic diverticulum worldwide. This report reviews and discusses the
      management of the appendiceal mucoceles. CONCLUSION: The incidence of colonic
      diverticula has recently begun to increase in Japan. The possibility of a
      mucocele within a colonic diverticulum should be considered in patients with
      submucosal colonic tumors.

PMID- 26318131
TI  - Correction of secondary deformity after Nuss procedure for pectus excavatum by
      means of cultured autologous cartilage cell injection.
AB  - INTRODUCTION: For some cases of pectus excavatum, ideal chest shape cannot be
      achieved solely by performing the Nuss procedure. This manuscript presents a case
      where the residual deformity following Nuss was corrected using injection
      transplantation of cultured autologous chondrocytes. PRESENTATION OF CASE: The
      treatment was performed for an 18-year-old male, who sought improvement of his
      chest shape after previously undergoing the Nuss procedure. A 1cm(2) auricular
      cartilage piece was harvested from his ear. Chondrocytes were isolated from the
      cartilage piece and were cultured. The cultured chondrocytes were processed into
      gel form and were injection-transplanted to the deformed region of the patient's
      chest. The grafted chondrocytes consolidated in one month, presenting elasticity
      equivalent to ordinary costal cartilage. The patient's chest remains in an
      optimal shape after a one-year postoperative follow up. DISCUSSION: Secondary
      correction of the chest deformity after previous operation for pectus excavatum
      is often tricky, because of the possible adhesion of the lungs or pericardium
      with the thoracic wall. Transplantation of cultured autologous chondrocytes does
      not require intra-thoracic maneuvers, and so is less invasive than other surgical
      interventions. Hence, priority can be placed, in some cases, on the chondrocyte
      transplantation rather than the re-correction of the thorax with the Nuss
      procedure or Ravitch procedure. CONCLUSION: Transplantation of cultured
      autologous chondrocytes is recommended as a useful option for secondary
      correction of chest deformity after the Nuss procedure.

PMID- 26318132
TI  - Preoperatively diagnosed case with co-existence of papillary thyroid carcinoma
      and cervical tuberculous lymphadenitis.
AB  - INTRODUCTION: Papillary thyroid cancer (PTC) is the most frequent histological
      subtype of thyroid cancer. The lymph node metastasis is found in a high
      proportion of patients with PTC at the time of surgery. In contrast, tuberculous
      lymphadenitis remains a common cause of cervical lymphadenopathy in Asian
      countries. PRESENTATION OF CASE: We present a 60-year-old woman with coexistence
      of papillary thyroid carcinoma (PTC) and cervical tuberculous lymphadenitis and
      to show the usefulness of fine-needle aspiration biopsy (FNAB) and quantiferon
      testing to distinguish a lymph node metastasis of PTC from tuberculous
      lymphadenitis. DISCUSSION: FNAB and quantiferon testing are useful tools to check
      if enlargement of cervical lymph node is due to tuberculous infection, and a
      surgical plan should be carefully determined to avoid unnecessary surgical
      complications and the spread of tuberculous infection. CONCLUSION: The
      coexistence of cervical tuberculosis should be considered in the etiology of an
      enlarged lymph node for patients with PTC.

PMID- 26318133
TI  - De novo hiatal hernia of the gastric tube after sleeve gastrectomy.
AB  - INTRODUCTION: Sleeve gastrectomy (SG) is a frequently used surgical procedure for
      the treatment of morbid obesity. Several complications of SG have been described;
      however, de novo hiatal hernia of the gastric tube, as a complication of SG, has
      not been described in the literature. PRESENTATION OF CASE: Here, we report a
      case of a hiatal hernia 2 years after SG. In the case reported here, the hiatal
      hernia was associated with weight regain. The mechanisms responsible for the
      herniation of the pouch are difficult to identify. Conversion from sleeve
      gastrectomy to Roux-en-Y gastric bypass is an effective treatment for this
      complication. Its management is safe and effective. DISCUSSION: Obesity itself is
      an independent risk factor for hiatal hernia, found preoperatively in more than
      half of the morbidly obese patients. This predisposition is explained by higher
      intra-gastric pressure due to intra-abdominal or visceral fat, reduced inferior
      oesophageal sphincter pressure, and oesophageal motility problems. CONCLUSION: To
      our knowledge, this is the first described case of hiatal hernia of the gastric
      tube after SG.

PMID- 26318134
TI  - Malignant eccrine breast spiradenoma. A case report and literature review.
AB  - INTRODUCTION: Eccrine spiradenomas are rare adnexal tumours of the skin that
      originate in the sweat glands. There are only three cases, including ours,
      diagnosed as malignant transformation in the breast. PRESENTATION OF CASE: We
      present a case of an asymptomatic 48 year old woman in whom the lesion was
      detected on the basis of breast cancer prevention programme. The metastatic study
      detection and the sentinel lymph node biopsy were negative so wide excision of
      the mass was performed with no further treatment. After 32 months of follow-up,
      there is no evidence of recurrent or metastatic disease in our patient.
      DISCUSSION: The lesions usually show a typical history of a long-standing
      unchanged cutaneous solitary nodule that becomes enlarged. The imaging findings
      of breast eccrine spiradenomas have not been clearly demonstrated. Diagnosis is
      based in histopathological findings of malignant focus. A large list of uncommon
      dermatological skin malignancies and breast benign lesions can mimic malignant
      eccrine spiradenomas (MES); therefore, determination of inmunophenotype allows
      narrowing differential diagnosis. Distant metastases portend an ominous
      prognosis. The mainstay of treatment is surgical removal with wide excision
      margins. Radiation and hyperthermic chemotherapy can also be administered to
      prevent focal recurrence. Due to the high risk of developing metastases, close
      follow up of these patients for early detection of recurrence should be carried
      out. CONCLUSION: Eccrine spiradenomas are rare adnexal tumours of the skin.
      Intraparenquimatous breast location is especially infrequent. Diagnosis is based
      on histopathological examination. MES metastasizes (40%), so a close follow up is
      recommended.

PMID- 26318135
TI  - "Puestow modified procedure in the era of advanced endoscopic interventions for
      the management of chronic lithiasic pancreatitis. A two cases report".
AB  - INTRODUCTION: Pancreatic duct calculi in chronic pancreatitis (CP) patients are
      the main cause of intractable pain which is their main symptom. Decompression
      options of for the main pancreatic duct are both surgical and advanced endoscopic
      procedures. PRESENTATION OF CASES: A 64-year-old male with known CP due to
      alcohol consumption and a 36-year-old female with known idiopathic CP and
      pancreatic duct calculi were managed recently in our hospital where endoscopic
      procedures were unsuccessful. A surgical therapy was considered and a
      longitudinal pancreaticojejunostomy (modified Puestow procedure) in both patients
      was performed with excellent results. DISCUSSION: Over the last 30 years,
      endoscopic procedures are developed to manage pancreatic duct strictures and
      calculi of the main pancreatic duct in CP patients. In both of our cases
      endoscopic therapy was first attempted but failed to extract the pancreatic duct
      stones, due to their size and speculations. Modified Puestow procedure was
      performed for both and it was successful for long term pain relief. CONCLUSION:
      Despite advancement in endoscopic interventions and less invasive therapies for
      the management of chronic lithiasic pancreatitis we consider that classic
      surgical management can be appropriate in certain cases.

PMID- 26318136
TI  - A peculiar case of large primary cutaneous Ewing's sarcoma of the foot: Case
      report and review of the literature.
AB  - INTRODUCTION: Primary cutaneous extraskeletal Ewing's sarcomas (ESs) are
      extremely rare tumors, limited to the skin and generally appear as a single small
      lesion, circumscribed mid-to-deep dermis or involving subcutis. Due to their
      rarity and morphological similarity to other cutaneous tumors, ESs are subject to
      being clinically and pathologically subdiagnosed. PRESENTATION OF CASE: A 37-year
      old man presented a large rapidly growing mass of the first toe measuring 9.5*8cm
      with no radiological evidence of bone involvement. The patient underwent wide
      surgical tumor resection; histological, immunohistochemical and molecular
      evaluation confirmed the diagnosis of ESs. Postoperative examinations revealed no
      metastasis and after 11 months follow-up no recurrences were detected.
      DISCUSSION: Current literature reports only a few isolated cases or small series.
      ESs are generally described as small masses with a favorable clinical behavior.
      Despite lower extremity is a relatively frequent site, only rare and small ESs of
      the foot have been reported. To our knowledge the present case is the largest ES
      of the foot. Despite its large size, the patient did not report any metastases
      confirming the hypothesis of treating superficial ES with surgery alone, thus
      avoiding adjuvant radiotherapy and/or chemotherapy and their related side
      effects. CONCLUSION: ESs still remain exceedingly rare tumors and they could not
      be taken in consideration into differential diagnosis. This case represents a
      peculiar example of large ES in an uncommon site as the foot successfully treated
      with surgery alone, and may serve as an alert for those physicians who approach
      such rapidly growing superficial lesions.

PMID- 26318137
TI  - Do rheumatologists know how to squeeze? Evaluations of Gaenslen's maneuver.
AB  - The Gaenslen's compression maneuver is the application of pressure on the
      metacarpophalangeal joints in order to evoke pain on a patient who has active
      synovitis. The results from the use of the maneuver are seen as controversial due
      to the lack of information describing the technique required for this procedure.
      The present study will aim to clarify uncertainty in regard to the form,
      pressure, and time required to apply the maneuver by rheumatologist.
      Rheumatologist were observed and monitored while performing the Gaenslen
      compression maneuver on a prosthetic, biomedical device. The device was shaped to
      mimic a human hand and equipped with a sensor to monitor the force and time of
      which the pressure was applied. One hundred and eight (62 %) participants gave a
      valid recording. From these, 121 (87.7 %) were made by certified rheumatologists.
      The most predominant method (104 physicians/75.4 %) of applying the maneuver was
      by using the right hand with superior approach. The median strength calculated in
      grams resulted in 299 gr (IQR 145) (range 150-741 gr). The median time expressed
      in milliseconds was of 956.6 ms (IQR 824.6) . This is the first study to assess a
      clinical maneuver in a qualitative and quantitative manner. The results from this
      study, more specifically the low number of usable recordings, and the wide range
      of force exerted in the squeeze test may explain the differences in sensitivity
      and specificity in clinical studies. 

PMID- 26318139
TI  - Estimating Fitness of Viral Quasispecies from Next-Generation Sequencing Data.
AB  - The quasispecies model is ubiquitous in the study of viruses. While having lead
      to a number of insights that have stood the test of time, the quasispecies model
      has mostly been discussed in a theoretical fashion with little support of data.
      With next-generation sequencing (NGS), this situation is changing and a wealth of
      data can now be produced in a time- and cost-efficient manner. NGS can, after
      removal of technical errors, yield an exceedingly detailed picture of the viral
      population structure. The widespread availability of cross-sectional data can be
      used to study fitness landscapes of viral populations in the quasispecies model.
      This chapter highlights methods that estimate the strength of selection in
      selective sweeps, assesses marginal fitness effects of quasispecies, and finally
      infers the fitness landscape of a viral quasispecies, all on the basis of NGS
      data. 

PMID- 26318138
TI  - What Is a Quasispecies? Historical Origins and Current Scope.
AB  - The quasispecies concept is introduced by means of a simple theoretical model
      that uses as little chemical kinetics and mathematics as possible but fully in
      the spirit of Albert Einstein who said: "Things should be made as simple as
      possible but not simpler." More elaborate treatments follow in the forthcoming
      chapters. It is shown that the most important results of the theory, in
      particular the existence of error thresholds, are not dependent on simplifying
      assumptions concerning the distribution of fitness values. Error thresholds are
      regularly found on landscapes with large and irregular scatter of fitness. After
      the introduction to theory, it will be shown how experimental data on the
      evolution of molecules or viruses may be fit to the theoretical model. 

PMID- 26318140
TI  - Expression Specificity of Disease-Associated lncRNAs: Toward Personalized
      Medicine.
AB  - Long noncoding RNAs (lncRNAs) perform diverse regulatory functions in
      transcription, translation' chromatin modification, and cellular organization.
      Misregulation of lncRNAs is found linked to various human diseases. Compared to
      protein-coding RNAs' lncRNAs are more specific to organs, tissues, cell types,
      developmental stages, and disease conditions' making them promising candidates as
      diagnostic and prognostic biomarkers and as gene therapy targets. The functional
      annotation of mammalian genome (FANTOM) consortium utilizes cap analysis of gene
      expression (CAGE) method to quantify genome-wide activities of promoters and
      enhancers of coding and noncoding RNAs across a large collection of human and
      mouse tissues' cell types' diseases, and time-courses. The project discovered
      widespread transcription of major lncRNA classes, including lncRNAs derived from
      enhancers' bidirectional promoters' antisense lncRNAs' and repetitive elements.
      Results from FANTOM project enable assessment of lncRNA expression specificity
      across tissue and disease conditions' based on differential promoter and enhancer
      usage. More than 85 % of disease-related SNPs are within noncoding regions and
      are strikingly overrepresented in enhancer and promoter regions, suggestive of
      the importance of lncRNA loci at these SNP harboring regions to human diseases.
      In this chapter' we discuss lncRNA expression specificity' review diverse
      functions of disease-associated lncRNAs' and present perspectives on their
      potential therapeutic applications for personalized medicine. The future
      development of lncRNA applications relies on technologies to identify and
      validate their functions' structures' and mechanisms. Comprehensive understanding
      of genome-wide interaction networks of lncRNAs with proteins, chromatins, and
      other RNAs in regulating cellular processes will allow personalized medicine to
      use lncRNAs as highly specific biomarkers in diagnosis' prognosis, and
      therapeutic targets. 

PMID- 26318141
TI  - Breast Cancer Screening Beliefs Questionnaire: Psychometric properties assessment
      of the Arabic version.
AB  - PURPOSE: The aim of the study was to report the psychometric properties of the
      Arabic version of the Breast Cancer Screening Beliefs Questionnaire (BCSBQ).
      METHODS: A convenience sample of 251 Arabic-Australian women was recruited from a
      number of Arabic community organizations. Construct validity was examined by
      Cuzick's non-parametric test while Cronbach alpha was used to assess internal
      consistency reliability. Explanatory factor analysis was conducted to study the
      factor structure. RESULTS: The results indicated that the Arabic version of the
      BCSBQ had satisfactory validity and internal consistency. The Cronbach's alpha of
      the three subscales ranged between 0.810 and 0.93. The frequency of breast cancer
      screening practices (breast awareness, clinical breast-examination and
      mammography) were significantly associated with attitudes towards general health
      check-up and perceived barriers to mammographic screening. Exploratory factor
      analysis showed a similar fit for the hypothesized three-factor structure with
      our data set. CONCLUSIONS: The Arabic version of the BCBSQ is a culturally
      appropriate, valid and reliable instrument for assessing the beliefs, knowledge
      and attitudes to breast cancer and breast cancer screening practices among Arabic
      Australian women.

PMID- 26318142
TI  - Inhibitory effects of a novel cationic dodecapeptide [CL(14-25)] derived from
      cyanate lyase of rice on endotoxic activities of LPSs from Escherichia coli and
      periodontopathic Aggregatibacter actinomycetemcomitans.
AB  - OBJECTIVE: CL(14-25), a dodecapeptide of cyanate lyase from rice, is a novel
      cationic alpha-helical antimicrobial peptide. In this study, we examined
      inhibitory ability of CL(14-25) against endotoxic activities of
      lipopolysaccharides (LPSs) from Escherichia coli and periodontal pathogenic
      Aggregatibacter actinomycetemcomitans. METHODS: Endotoxin-neutralizing activity
      of CL(14-25) was evaluated by inhibition to induction of cytokine and nitric
      oxide in human aortic endothelial cells (HAECs) and RAW264 mouse macrophage
      cells, respectively. Protective effect of CL(14-25) was determined in mice
      against lethal toxicity of LPS. RESULTS: IL-6 in HAECs was induced by stimulation
      with LPS preparations of A. actinomycetemcomitans and E. coli tested in this
      study, and addition of CL(14-25) to the medium caused inhibition of their
      induction in a dose-dependent manner. CL(14-25) inhibited NO induction in RAW264
      cells by a smooth type LPS of E. coli O55:B5 and an Rc type LPS of E. coli J5 as
      well as lipid A of E. coli R515 in a dose-dependent manner. Simultaneous
      injection of E. coli O55:B5 LPS and CL(14-25) in BALB/c mice resulted in
      prevention of lethal toxicity of the former. The results of a Limulus amebocyte
      lysate assay and surface plasmon resonance analysis of interaction between CL(14
      25) and E. coli LPS or lipid A showed that CL(14-25) specifically binds to a
      lipid A moiety of LPS. CONCLUSION: The results of present study suggest that
      CL(14-25) has a potential to be used as a nutraceutical agent for periodontal
      therapy.

PMID- 26318143
TI  - Different responses of low grain-Cd-accumulating and high grain-Cd-accumulating
      rice cultivars to Cd stress.
AB  - Cadmium (Cd) is a major heavy metal pollutant which is highly toxic to plants and
      animals. The accumulation of Cd in rice grains is a major agricultural problem in
      regions with Cd pollution. A hydroponics experiment using low grain-Cd
      accumulating rice (xiushui 11) and high grain-Cd-accumulating rice (xiushui 110)
      was carried out to characterize the different responses of rice cultivars to Cd
      stress. We found that xiushui 11 was more tolerant to Cd than xiushui 110, and
      xiushui 11 suffered less oxidative damage. Cell walls played an important role in
      limiting the amount of Cd that entered the protoplast, especially in xiushui 11.
      Cd stored in organelles as soluble fractions, leading to greater physiological
      stress of Cd detoxification. We found that Cd can disturb the ion homeostasis in
      rice roots because Cd(2+) and Ca(2+) may have a similar uptake route. Xiushui 11
      had a faster root-to-shoot transport of Cd, and the expression level of OsPCR1
      gene which was predicted related with Cd accumulation in rice was consist with
      the Cd transport of root-to-shoot in rice and maintain the greater Cd tolerance
      of xiushui 11. These results suggest there are different Cd detoxification and
      accumulation mechanisms in rice cultivars. 

PMID- 26318144
TI  - Reduction of copper phytotoxicity by liming: A study of the root anatomy of young
      vines (Vitis labrusca L.).
AB  - Frequent applications of copper (Cu)-based fungicides on vines causes the
      accumulation of this metal in vineyard soils, which can cause toxicity in young
      vines. However, liming may reduce these toxic effects. The present study aimed to
      evaluate the effects of Cu toxicity on the root anatomy of young vines and the
      alleviation of Cu toxicity by lime applications to contaminated sandy soil. The
      treatments consisted of the addition of lime (0.0, 1.5 and 3.0 Mg ha(-1)) and two
      Cu concentrations (0 and 50 mg kg(-1)) to Typic Hapludalf soil. Young vines
      'Niagara Branca' (Vitis labrusca L.) were obtained by micropropagation and
      cultivated for 70 days. The young vines grown with Cu and without liming
      presented a disorganized root structure; reduced root cap size; increased
      diameter (47%), cortex area (128%), vascular cylinder area (93%), and number of
      cortical layers and cells containing phenolic compounds (132%); and reduced root
      (41%), stem (44%) and leaf dry mass (21%) and height increase (55%). Moreover, Cu
      exposure reduced Ca concentrations (13%) and increased Cu concentrations (371%)
      in the roots. Liming, primarily with the highest tested dose, increased the soil
      pH (from 4.4 to 5.4-6.1), decreased the Cu concentration in the soil (extracted
      by CaCl2), increased the calcium (Ca) and magnesium (Mg) uptake by plants,
      prevented root anatomical changes and benefited young vine growth in soil with
      higher Cu concentrations.

PMID- 26318146
TI  - Ca(2+) and CaM are involved in Al(3+) pretreatment-promoted fluoride accumulation
      in tea plants (Camellia sinesis L.).
AB  - Tea plant (Camellia sinensis (L.) O. kuntze) is known to be a fluoride (F) and
      aluminum (Al(3+)) hyper-accumulator. Previous study showed that pre-treatment of
      Al(3+) caused a significant increase of F accumulation in tea plants. However,
      less is known about the intricate network of Al(3+) promoted F accumulation in
      tea plants. In this study, the involvement of endogenous Ca(2+) and CaM in Al(3+)
      pretreatment-promoted F accumulation in tea plants was investigated. Our results
      showed that Al(3+) induced the inverse change of intracellular Ca(2+)
      fluorescence intensity and stimulated Ca(2+) trans-membrane transport in the
      mature zone of tea root. Also, a link between internal Ca(2+) and CaM was found
      in tea roots under the presence of Al(3+). In order to investigate whether Ca(2+)
      and CaM were related to F accumulation promoted by Al(3+) pretreatment, Ca(2+)
      chelator EGTA and CaM antagonists CPZ and TFP were used. EGTA, CPZ, and TFP
      pretreatment inhibited Al(3+)-induced increase of Ca(2+) fluorescence intensity
      and CaM content in tea roots, and also significantly reduced Al(3+)-promoted F
      accumulation in tea plants. Taken together, our results suggested that the
      endogenous Ca(2+) and CaM are involved in Al(3+) pretreatment-promoted F
      accumulation in tea roots. 

PMID- 26318145
TI  - A biochar application protects rice pollen from high-temperature stress.
AB  - The influences of high temperature and fertilization with biochar and phosphorus
      (P) on the pollen characteristics of two rice cultivars (IR-64 and Huanghuazhan)
      were examined in controlled growth chambers. Temperature treatments included high
      daytime temperature (HDT), high nighttime temperature (HNT) and ambient
      temperature (AT). The fertilization treatments were control, biochar alone, P
      alone and biochar + P. High temperature severely reduced pollen fertility, anther
      dehiscence, pollen retention and pollen germination of both rice cultivars, with
      HNT more destructive than HDT. The Huanghuazhan cultivar performed better than IR
      64 under high temperature, with higher pollen fertility, better anther dehiscence
      and greater pollen retention and germination rates. In both cultivars, the pollen
      of plants treated with biochar + P were more resistant to heat induced stress.
      Further studies are needed to test the ability of biochar to ameliorate the
      effects of different abiotic stresses in rice and other crops.

PMID- 26318147
TI  - Subcellular localization and internalization of the vasopressin V1B receptor.
AB  - Only limited information is available on agonist-dependent changes in the
      subcellular localization of vasopressin V1B receptors. Our radioligand binding
      study of membrane preparations and intact cells revealed that a large fraction of
      the V1B receptor is located in the cytoplasm in unstimulated CHO cells, which is
      in contrast to the plasma membrane localization of the V1A and V2 receptors.
      Moreover, when the affinity of radiolabeled arginine-vasopressin ([3H]AVP) was
      compared between membrane preparations and intact cells, the affinity of [3H]AVP
      to the cell surface V1B receptors, but not the V1A receptors, was significantly
      reduced. Although the number and affinity of cell surface V1B receptors
      decreased, they became extensively internalized upon binding with [3H]AVP.
      Approximately 87% of cell surface-bound [3H]AVP was internalized and became
      resistant to acid wash during incubation with 1 nM [3H]AVP. By contrast, less
      ligand (35%) was internalized in the cells expressing the V1A receptor. Extensive
      internalization of the V1B receptors was partially attenuated by inhibitors of
      cytoskeletal proteins, siRNA against beta-arrestin 2, or the removal of sodium
      chloride from the extracellular buffer, indicating that this internalization
      involves clathrin-coated pits. Together, these results indicate that the
      mechanism that regulates the number and affinity of V1B receptors in the plasma
      membrane is markedly distinct from the corresponding mechanisms for the V1A and
      V2 receptors and plays a critical role under stress conditions, when vasopressin
      release is augmented.

PMID- 26318148
TI  - Genetic inactivation and prolonged pharmacologic inhibition of monoacylglycerol
      lipase have opposite effects on anesthetic sensitivity to propofol.
AB  - Monoacylglycerol lipase (MGL) is a major enzyme involved in degradation of the
      endocannabinoid 2-arachidonoylglycerol (2-AG). Selective inhibitors of MGL are
      regarded as promising analgesics and anticancer agents. To gain insight into the
      possible consequences of their prolonged administration for anesthetic action,
      the effects of several inhalational and intravenous anesthetics were tested in
      knockout mice lacking the MGL gene in the loss of righting reflex (LORR) assay.
      Sensitivity to inhalational and most intravenous anesthetics was not altered in
      knockout mice. However, compared with wild-type littermates, they showed
      increased sensitivity to the intravenous anesthetic propofol. Permanently
      elevated levels of 2-AG after MGL knockout are known to cause desensitization of
      cannabinoid (CB1) receptors, which have been advocated as possible mediators of
      propofol anesthesia. Therefore, increased sensitivity to propofol in knockout
      mice at first suggested that 2-AG may potentiate CB1 receptors despite their
      hypofunction in these animals. Pharmacologic inhibition of MGL also causes
      desensitization of CB1 receptors, so sensitivity to propofol was tested further
      in C57BL/6N mice pretreated chronically with the selective MGL inhibitor JZL 184.
      Contrary to the results in knockout mice, these animals showed drastically
      reduced sensitivity to propofol. The reason for increased sensitivity to propofol
      after MGL knockout remains unclear, but may result from changes occurring in
      these animals during development. However, our results in C57BL/6N mice
      pretreated with JZL 184 confirmed the role of CB1 receptors in propofol
      anesthesia advocated previously, and also suggest that prolonged use of MGL
      inhibitors may be associated with the development of resistance to propofol. 

PMID- 26318149
TI  - Childhood Maltreatment and Sexual Risk Taking: The Mediating Role of Alexithymia.
AB  - Childhood maltreatment is a significant predictor of sexual risk taking. The
      nature of this relationship is not fully understood; however, emotion
      dysregulation may play an important role. We tested the role of difficulty
      identifying and describing feelings (i.e., alexithymia) on the relationship
      between childhood maltreatment and sexual risk taking. Specifically, we
      hypothesized two mechanisms, one in which alexithymia is related to sexual risk
      taking via negative urgency and alcohol use and a second one in which alexithymia
      is related to sexual risk taking via neediness. The participants for this study
      were 425 sexually active college undergraduates (303 females, 122 males) between
      the ages of 18 and 25 years. The results of a structural equation model indicated
      that alexithymia accounted for a significant part of the relationship between
      child maltreatment and sexual risk behavior. Moreover, the relationship between
      alexithymia and sexual risk taking was fully accounted for by two separate paths.
      First, negative urgency and subsequent alcohol use partially mediated the
      relationship, and the second effect was accounted for by needy interpersonal
      style. Adverse experiences during childhood can impair emotional functioning and
      contribute to behavioral and interpersonal dysregulation. 

PMID- 26318150
TI  - Ethical criticism starts with reading carefully: reply to Veale (2015).

PMID- 26318151
TI  - Maternal supplementation with conjugated linoleic acid in the setting of diet
      induced obesity normalises the inflammatory phenotype in mothers and reverses
      metabolic dysfunction and impaired insulin sensitivity in offspring.
AB  - Maternal consumption of a high-fat diet significantly impacts the fetal
      environment and predisposes offspring to obesity and metabolic dysfunction during
      adulthood. We examined the effects of a high-fat diet during pregnancy and
      lactation on metabolic and inflammatory profiles and whether maternal
      supplementation with the anti-inflammatory lipid conjugated linoleic acid (CLA)
      could have beneficial effects on mothers and offspring. Sprague-Dawley rats were
      fed a control (CD; 10% kcal from fat), CLA (CLA; 10% kcal from fat, 1% total fat
      as CLA), high-fat (HF; 45% kcal from fat) or high fat with CLA (HFCLA; 45% kcal
      from fat, 1% total fat as CLA) diet ad libitum 10days prior to and throughout
      gestation and lactation. Dams and offspring were culled at either late gestation
      (fetal day 20, F20) or early postweaning (postnatal day 24, P24). CLA, HF and
      HFCLA dams were heavier than CD throughout gestation. Plasma concentrations of
      proinflammatory cytokines interleukin-1beta and tumour necrosis factor-alpha were
      elevated in HF dams, with restoration in HFCLA dams. Male and female fetuses from
      HF dams were smaller at F20 but displayed catch-up growth and impaired insulin
      sensitivity at P24, which was reversed in HFCLA offspring. HFCLA dams at P24 were
      protected from impaired insulin sensitivity as compared to HF dams. Maternal CLA
      supplementation normalised inflammation associated with consumption of a high-fat
      diet and reversed associated programming of metabolic dysfunction in offspring.
      This demonstrates that there are critical windows of developmental plasticity in
      which the effects of an adverse early-life environment can be reversed by
      maternal dietary interventions. 

PMID- 26318152
TI  - Textiloma (gossypiboma) mimicking recurrent intracranial abscess.
AB  - INTRODUCTION: Cranial-retained surgical sponges (gossypiboma or textiloma) are
      rare incidents and mostly asymptomatic. However, they can be confused with other
      masses such as a hematoma abscess or tumor. During early stages, some
      gossypibomas can cause infection or abscess formation. CASE PRESENTATION: A 22
      year-old Turkish female who had frontal lobe brain surgery to remove an abscess 2
      months previously was admitted with complaints of headache and vomiting.
      CONCLUSION: Gossypiboma was confirmed in the patient. Following cranial surgery,
      gossypiboma should be considered as a differential diagnosis of recurrence of
      previous surgical operations.

PMID- 26318153
TI  - Nuclear heterogeneous nuclear ribonucleoprotein D is associated with poor
      prognosis and interactome analysis reveals its novel binding partners in oral
      cancer.
AB  - BACKGROUND: Post-transcriptional regulation by heterogeneous ribonucleoproteins
      (hnRNPs) is an important regulatory paradigm in cancer development. Our proteomic
      analysis revealed hnRNPD overexpression in oral dysplasia as compared with normal
      mucosa; its role in oral carcinogenesis remains unknown. Here in we determined
      the hnRNPD associated protein networks and its clinical significance in oral
      squamous cell carcinoma (OSCC). METHODS: Immunoprecipitation (IP) followed by
      tandem mass spectrometry was used to identify the binding partners of hnRNPD in
      oral cancer cell lines. Ingenuity pathway analysis (IPA) was carried out to
      unravel the protein interaction networks associated with hnRNPD and key
      interactions were confirmed by co-IP-western blotting. hnRNPD expression was
      analyzed in 183 OSCCs, 44 oral dysplasia and 106 normal tissues using
      immunohistochemistry (IHC) and correlated with clinico-pathological parameters
      and follow up data over a period of 91 months. Kaplan-Meier survival and Cox
      multivariate-regression analyses were used to evaluate the prognostic
      significance of hnRNPD in OSCC. RESULTS: We identified 345 binding partners of
      hnRNPD in oral cancer cells. IPA unraveled novel protein-protein interaction
      networks associated with hnRNPD and suggested its involvement in multiple
      cellular processes: DNA repair, replication, chromatin remodeling, cellular
      proliferation, RNA splicing and stability, thereby directing the fate of oral
      cancer cells. Protein-protein interactions of hnRNPD with 14-3-3zeta, hnRNPK and
      S100A9 were confirmed using co-IP-western blotting. IHC analysis showed
      significant overexpression of nuclear hnRNPD in oral dysplasia [p = 0.001, Odds
      ratio (OR) = 5.1, 95% CI = 2.1-11.1) and OSCCs (p = 0.001, OR = 8.1, 95% CI = 4.5
      14.4) in comparison with normal mucosa. OSCC patients showing nuclear hnRNPD
      overexpression had significantly reduced recurrence free survival [p = 0.026,
      Hazard ratio = 1.95, 95% CI = 1.0-3.5] by Kaplan-Meier survival and Cox
      multivariate-regression analyses and has potential to define a high-risk subgroup
      among OSCC patients with nodal negative disease. CONCLUSIONS: Our findings
      suggest novel functions of hnRNPD in cellular proliferation and survival, besides
      RNA splicing and stability in oral cancer. Association of nuclear hnRNPD with
      poor prognosis in OSCC patients taken together with its associated protein
      networks in oral cancer warrant future studies designed to explore its potential
      as a plausible novel target for molecular therapeutics.

PMID- 26318154
TI  - Gramella aquimixticola sp. nov., isolated from water of an estuary environment.
AB  - A Gram-stain-negative, aerobic, non-spore-forming bacterial strain, motile by
      gliding and with rod-shaped or ovoid cells, was isolated from water of an estuary
      environment at Hwajinpo, South Korea. The strain was designated HJM-19T and
      subjected to a polyphasic taxonomic study. The novel strain grew optimally at 30 
      degrees C, at pH 7.0-8.0 and in the presence of 1.0-2.0 % (w/v) NaCl.
      Phylogenetic trees based on 16S rRNA gene sequences revealed that strain HJM-19T
      belongs to the genus Gramella. It exhibited 16S rRNA gene sequence similarity
      values of 97.2-98.1 % to the type strains of Gramella portivictoriae, Gramella
      aestuariivivens, Gramella marina, Gramella echinicola and Gramella aestuarii, and
      of 93.9-96.5 % to the type strains of the other species of the genus Gramella
      with validly published names. Strain HJM-19T contained MK-6 as the predominant
      menaquinone and anteiso-C15 : 0, anteiso-C17 : 1omega9c and C17 : 0 2-OH as the
      major fatty acids. The major polar lipids of strain HJM-19T were
      phosphatidylethanolamine and two unidentified lipids. The DNA G+C content of
      strain HJM-19T was 48.0 mol%, and its DNA-DNA relatedness values with the type
      strains of the five phylogenetically closely related species of the genus
      Gramella were 11-23 %. The differential phenotypic properties, together with the
      phylogenetic and genetic distinctiveness, revealed that strain HJM-19T is
      separated from other species of the genus Gramella. On the basis of the data
      presented, strain HJM-19T is considered to represent a novel species of the genus
      Gramella, for which the name Gramella aquimixticola sp. nov. is proposed. The
      type strain is HJM-19T ( = KCTC 42706T = NBRC 111224T).

PMID- 26318156
TI  - The Value of Mentorship.
AB  - The recent Young Physicians needs assessment survey identified mentorship as the
      single greatest need for this demographic, which includes physicians under 40
      years of age or in their first 8 years of practice after completion of training.
      Much has been written in textbooks and other journals about mentorship, and as
      young physicians are certainly not alone in this need, mentorship has become a
      key focus of future Academy endeavors. Serving as Chair of the Young Physicians
      Section over the past year has afforded me the opportunity to interact with a
      variety of dynamic and engaging leaders in our Academy, and herein I provide a
      synopsis of what these experiences have taught me as well as provide some of the
      most important pearls that I have picked up along the way. 

PMID- 26318155
TI  - SNP Assay Development for Linkage Map Construction, Anchoring Whole-Genome
      Sequence, and Other Genetic and Genomic Applications in Common Bean.
AB  - A total of 992,682 single-nucleotide polymorphisms (SNPs) was identified as ideal
      for Illumina Infinium II BeadChip design after sequencing a diverse set of 17
      common bean (Phaseolus vulgaris L) varieties with the aid of next-generation
      sequencing technology. From these, two BeadChips each with >5000 SNPs were
      designed. The BARCBean6K_1 BeadChip was selected for the purpose of optimizing
      polymorphism among market classes and, when possible, SNPs were targeted to
      sequence scaffolds in the Phaseolus vulgaris 14* genome assembly with sequence
      lengths >10 kb. The BARCBean6K_2 BeadChip was designed with the objective of
      anchoring additional scaffolds and to facilitate orientation of large scaffolds.
      Analysis of 267 F2 plants from a cross of varieties Stampede * Red Hawk with the
      two BeadChips resulted in linkage maps with a total of 7040 markers including
      7015 SNPs. With the linkage map, a total of 432.3 Mb of sequence from 2766
      scaffolds was anchored to create the Phaseolus vulgaris v1.0 assembly, which
      accounted for approximately 89% of the 487 Mb of available sequence scaffolds of
      the Phaseolus vulgaris v0.9 assembly. A core set of 6000 SNPs (BARCBean6K_3
      BeadChip) with high genotyping quality and polymorphism was selected based on the
      genotyping of 365 dry bean and 134 snap bean accessions with the BARCBean6K_1 and
      BARCBean6K_2 BeadChips. The BARCBean6K_3 BeadChip is a useful tool for genetics
      and genomics research and it is widely used by breeders and geneticists in the
      United States and abroad. 

PMID- 26318157
TI  - Hepatic overexpression of methionine sulfoxide reductase A reduces
      atherosclerosis in apolipoprotein E-deficient mice.
AB  - Methionine sulfoxide reductase A (MsrA), a specific enzyme that converts
      methionine-S-sulfoxide to methionine, plays an important role in the regulation
      of protein function and the maintenance of redox homeostasis. In this study, we
      examined the impact of hepatic MsrA overexpression on lipid metabolism and
      atherosclerosis in apoE-deficient (apoE(-/-)) mice. In vitro study showed that in
      HepG2 cells, lentivirus-mediated human MsrA (hMsrA) overexpression upregulated
      the expression levels of several key lipoprotein-metabolism-related genes such as
      liver X receptor alpha, scavenger receptor class B type I, and ABCA1. ApoE(-/-)
      mice were intravenously injected with lentivirus to achieve high-level hMsrA
      expression predominantly in the liver. We found that hepatic hMsrA expression
      significantly reduced plasma VLDL/LDL levels, improved plasma superoxide
      dismutase, and paraoxonase-1 activities, and decreased plasma serum amyloid A
      level in apoE(-/-) mice fed a Western diet, by significantly altering the
      expression of several genes in the liver involving cholesterol selective uptake,
      conversion and excretion into bile, TG biosynthesis, and inflammation. Moreover,
      overexpression of hMsrA resulted in reduced hepatic steatosis and aortic
      atherosclerosis. These results suggest that hepatic MsrA may be an effective
      therapeutic target for ameliorating dyslipidemia and reducing atherosclerosis
      related cardiovascular diseases. 

PMID- 26318159
TI  - Cross-cultural and Moroccan Validation of the University of Washington Quality of
      Life Questionnaire for Patients With Head and Neck Cancer.
AB  - OBJECTIVES: To translate the original English version of the University of
      Washington Quality of Life (UW-QOL) questionnaire into Moroccan Arabic version
      and investigate its psychometric validity and reliability for Moroccan-speaking
      patients with head and neck cancer. METHODS: The UW-QOL was conducted in 104
      patients treated for head and neck cancer in the department of head and neck
      surgery, Ibn Rochd university hospital, Casablanca. A control group of 57 healthy
      volunteers was also evaluated. The questionnaire was translated into Moroccan
      language. RESULTS: Cronbach's alpha coefficient was 0.829, suggesting good
      internal consistency, and test-retest reliability was excellent (intraclass
      correlation coefficient [ICC] = 0.987). A good correlation was observed between
      UW-QOL composite scores and European Organization for Research and Treatment of
      Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) global health
      status/QOL scores (P < .001). There was also low concordance between the UW-QOL
      scores and the Physical Component Summary and Mental Component Summary scores of
      the 36-Item Short-Form questionnaire (SF-36) (P = .017 and P = .014,
      respectively). CONCLUSIONS: The Moroccan UW-QOL questionnaire appears to be
      culturally appropriate and psychometrically valid.

PMID- 26318158
TI  - Mesothelioma among Motor Vehicle Mechanics: An Updated Review and Meta-analysis.
AB  - BACKGROUND: We published a meta-analysis of the association between work as a
      motor vehicle mechanic and mesothelioma in 2004. Since then, several relevant
      studies on this topic have been published. Thus, to update the state-of-the
      science on this issue, we conducted a new systematic review and meta-analysis.
      METHODS: A comprehensive PubMed literature search through May 2014 was conducted
      to identify studies that reported relative risk estimates for mesothelioma among
      motor vehicle mechanics (in general), and those who were engaged in brake repair
      (specifically). Studies were scored and classified based on study
      characteristics. Random-effects meta-analyses generated summary relative risk
      estimates (SRREs) and corresponding 95% confidence intervals (CI). Heterogeneity
      of results was examined by calculating Q-test P-values (P-H) and I (2) estimates.
      Sub-group and sensitivity analyses were conducted for relevant study
      characteristics and quality measures. RESULTS: Ten case-control studies, one
      cohort study, and five proportionate mortality ratio (PMR)/standardized mortality
      odds ratio (SMOR) studies were identified and included in the quantitative
      assessment. Most meta-analysis models produced SRREs below 1.0, and no
      statistically significant increases in mesothelioma were observed. The SRRE for
      all studies was 0.80 (95% CI: 0.61-1.05) with significant heterogeneity (P-H
      <0.001, I (2) = 62.90). A similar SRRE was observed among the five Tier 1 studies
      with the highest quality ratings (SRRE = 0.76, 95% CI: 0.46-1.25), with no
      heterogeneity among studies (P-H = 0.912, I (2) = 0.00). Meta-analysis of the
      Tier 2 (n = 5) and Tier 3 (n = 6) studies resulted in SRREs of 1.09 (95% CI: 0.76
      1.58) and 0.73 (95% CI: 0.49-1.08), respectively. Restricting the analysis to
      Tiers 1 and 2 combined resulted in an SRRE of 0.92 (95% CI: 0.72-1.29). The SRRE
      specific to brake work (n = 4) was 0.64 (95% CI: 0.38-1.09). CONCLUSIONS: This
      meta-analysis of the epidemiologic studies provides evidence that motor vehicle
      mechanics, including workers who were engaged in brake repair, are not at an
      increased risk of mesothelioma.

PMID- 26318160
TI  - Around 9% of patients with ischaemic stroke are suitable for thrombectomy.

PMID- 26318161
TI  - 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary
      hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary
      Hypertension of the European Society of Cardiology (ESC) and the European
      Respiratory Society (ERS): Endorsed by: Association for European Paediatric and
      Congenital Cardiology (AEPC), International Society for Heart and Lung
      Transplantation (ISHLT).
AB  - Guidelines summarize and evaluate all available evidence on a particular issue at
      the time of the writing process, with the aim of assisting health professionals
      in selecting the best management strategies for an individual patient with a
      given condition, taking into account the impact on outcome, as well as the risk
      benefit ratio of particular diagnostic or therapeutic means. Guidelines and
      recommendations should help health professionals to make decisions in their daily
      practice. However, the final decisions concerning an individual patient must be
      made by the responsible health professional(s) in consultation with the patient
      and caregiver as appropriate. 

PMID- 26318162
TI  - Effectiveness, cost-effectiveness and cost-benefit of a single annual
      professional intervention for the prevention of childhood dental caries in a
      remote rural Indigenous community.
AB  - BACKGROUND: The aim of the study is to reduce the high prevalence of tooth decay
      in children in a remote, rural Indigenous community in Australia, by application
      of a single annual dental preventive intervention. The study seeks to (1) assess
      the effectiveness of an annual oral health preventive intervention in slowing the
      incidence of dental caries in children in this community, (2) identify the
      mediating role of known risk factors for dental caries and (3) assess the cost
      effectiveness and cost-benefit of the intervention. METHODS/DESIGN: The
      intervention is novel in that most dental preventive interventions require
      regular re-application, which is not possible in resource constrained
      communities. While tooth decay is preventable, self-care and healthy habits are
      lacking in these communities, placing more emphasis on health services to deliver
      an effective dental preventive intervention. Importantly, the study will assess
      cost-benefit and cost-effectiveness for broader implementation across similar
      communities in Australia and internationally. DISCUSSION: There is an urgent need
      to reduce the burden of dental decay in these communities, by implementing
      effective, cost-effective, feasible and sustainable dental prevention programs.
      Expected outcomes of this study include improved oral and general health of
      children within the community; an understanding of the costs associated with the
      intervention provided, and its comparison with the costs of allowing new lesions
      to develop, with associated treatment costs. Findings should be generalisable to
      similar communities around the world. The research is registered with the
      Australian New Zealand Clinical Trials Registry (ANZCTR), registration number
      ACTRN12615000693527; date of registration: 3rd July 2015.

PMID- 26318163
TI  - Suicidal ideation and suicide attempts in older adults: Influences of chronic
      illness, functional limitations, and pain.
AB  - This study aimed to examine the associations between suicidal behavior in older
      Korean adults and chronic illnesses, functional limitations, and pain. Data were
      obtained and analyzed for 8500 adults over 65 years of age from the 2007-2012
      Korea National Health and Nutrition Examination Survey IV and V. Multivariate
      logistic regression analyses were conducted to examine the associations between
      suicidal behavior, chronic illness, functional limitations, and pain. The
      presence of arthritis and renal failure were significantly associated with a
      higher risk of suicidal ideation and suicide attempts. Moderate limitation in
      usual activities and extreme pain significantly increased the risk of both
      suicidal ideation and suicide attempts, over and above the existence of chronic
      illnesses and depression status. 

PMID- 26318164
TI  - Reply to Dimitrov et al.: VelociSuite technologies are a foundation for rapid
      therapeutic antibody development.

PMID- 26318165
TI  - No evidence for a superior platform to develop therapeutic antibodies rapidly in
      response to MERS-CoV and other emerging viruses.

PMID- 26318167
TI  - Protein conformation in a vaccine matters.

PMID- 26318166
TI  - PDK1 induces JunB, EMT, cell migration and invasion in human gallbladder cancer.
AB  - The protein 3-phosphoinositide-dependent protein kinase 1 (PDK1) is upregulated
      in cancer. Here we showed that PDK1 stimulated cell proliferation, invasion and
      metastasis in gallbladder cancer (GBC), by inducing JunB and epithelial
      mesenchymal transition. JunB levels were increased in GBC samples and positively
      correlated with PDK1 levels in tumors. High levels of JunB predicted poor overall
      survival in GBC patients. Thus, PDK1 functions as a tumor promoter in human GBC
      by upregulating JunB. 

PMID- 26318168
TI  - Defensins versus pathogens: an unfolding story.

PMID- 26318169
TI  - Multidimensional extended spatial evolutionary games.
AB  - The goal of this paper is to study the classical hawk-dove model using mixed
      spatial evolutionary games (MSEG). In these games, played on a lattice, an
      additional spatial layer is introduced for dependence on more complex parameters
      and simulation of changes in the environment. Furthermore, diverse polymorphic
      equilibrium points dependent on cell reproduction, model parameters, and their
      simulation are discussed. Our analysis demonstrates the sensitivity properties of
      MSEGs and possibilities for further development. We discuss applications of
      MSEGs, particularly algorithms for modelling cell interactions during the
      development of tumours. 

PMID- 26318170
TI  - Traumatic andropause after combat injury.
AB  - In association with lower extremity amputation, complex genitourinary injuries
      have emerged as a specific challenge in modern military trauma surgery.
      Testicular injury or loss has profound implications for the recovering
      serviceman, in terms of hormone production and future fertility. The initial
      focus of treatment for patients with traumatic testicular loss is haemostasis,
      resuscitation and management of concurrent life-threatening injuries. Multiple
      reoperations are commonly required to control infection in combat wounds; in a
      review of 300 major lower extremity amputations, 53% of limbs required revisional
      surgery, with infection the commonest indication. Atypical infections, such as
      invasive fungal organisms, can also complicate military wounding. We report the
      case of a severely wounded serviceman with complete traumatic andropause, whose
      symptomatic temperature swings were initially mistaken for signs of occult
      sepsis. 

PMID- 26318172
TI  - Kallmann's syndrome: a visual vignette.

PMID- 26318171
TI  - Polyomavirus nephropathy of the native kidney in a patient with rheumatoid
      arthritis and pulmonary fibrosis.
AB  - Polyomavirus nephropathy is commonly seen in the renal allograft setting but is
      uncommon in native kidneys. This paper describes polyomavirus nephropathy that
      developed in the native kidneys of a patient following immunosuppressive therapy
      for rheumatoid arthritis/Sjogren's syndrome associated lung disease. The patient
      presented with dyspnoea and a slow steady rise in serum creatinine. Owing to
      chronic immunosuppression, calcineurin-inhibitor toxicity was suspected. However,
      renal biopsy revealed polyomavirus nephropathy. The treatment of choice, lowered
      immunosuppression, was complicated by exacerbation of the patient's lung disease.
      This case highlights features of polyomavirus nephropathy in the native kidney,
      as well as the difficulty in its treatment when immunosuppressive treatment is
      necessary for medical comorbidities. 

PMID- 26318173
TI  - Automatic estimation of midline shift in patients with cerebral glioma based on
      enhanced voigt model and local symmetry.
AB  - Cerebral glioma is one of the most aggressive space-occupying diseases, which
      will exhibit midline shift (MLS) due to mass effect. MLS has been used as an
      important feature for evaluating the pathological severity and patients' survival
      possibility. Automatic quantification of MLS is challenging due to deformation,
      complex shape and complex grayscale distribution. An automatic method is proposed
      and validated to estimate MLS in patients with gliomas diagnosed using magnetic
      resonance imaging (MRI). The deformed midline is approximated by combining
      mechanical model and local symmetry. An enhanced Voigt model which takes into
      account the size and spatial information of lesion is devised to predict the
      deformed midline. A composite local symmetry combining local intensity symmetry
      and local intensity gradient symmetry is proposed to refine the predicted midline
      within a local window whose size is determined according to the pinhole camera
      model. To enhance the MLS accuracy, the axial slice with maximum MSL from each
      volumetric data has been interpolated from a spatial resolution of 1 mm to 0.33
      mm. The proposed method has been validated on 30 publicly available clinical head
      MRI scans presenting with MLS. It delineates the deformed midline with maximum
      MLS and yields a mean difference of 0.61 +/- 0.27 mm, and average maximum
      difference of 1.89 +/- 1.18 mm from the ground truth. Experiments show that the
      proposed method will yield better accuracy with the geometric center of pathology
      being the geometric center of tumor and the pathological region being the whole
      lesion. It has also been shown that the proposed composite local symmetry
      achieves significantly higher accuracy than the traditional local intensity
      symmetry and the local intensity gradient symmetry. To the best of our knowledge,
      for delineation of deformed midline, this is the first report on both
      quantification of gliomas and from MRI, which hopefully will provide valuable
      information for diagnosis and therapy. The study suggests that the size of the
      whole lesion and the location of tumor (instead of edema or the sum of edema and
      tumor) are more appropriate to determine the extent of deformation. Composite
      local symmetry is recommended to represent the local symmetry around the deformed
      midline. The proposed method could be potentially used to quantify the severity
      of patients with cerebral gliomas and other brain pathology, as well as to
      approximate midsagittal surface for brain quantification. 

PMID- 26318174
TI  - A coiled-coil motif in non-structural protein 3 (NS3) of bluetongue virus forms
      an oligomer.
AB  - Bluetongue, an arthropod-borne non-contagious hemorrhagic disease of small
      ruminants, is caused by bluetongue virus (BTV). Several structural and non
      structural proteins encoded by BTV have been associated with virulence
      mechanisms. In the present study, the NS3 protein sequences of bluetongue viral
      serotypes were analyzed for the presence of heptad regions and oligomer
      formation. Bioinformatic analysis of NS3 sequences of all 26 BTV serotypes
      revealed the presence of at least three coiled-coil motifs (CCMs). A conserved
      alpha-helical heptad sequence was identified at 14-26 aa (CCM-I), 185-198aa (CCM
      II), and 94-116 aa (CCM-III). Among these, CCM-I occurs close to the N-terminus
      of NS3 and was presumed to be involved in oligomerization. Furthermore, the N
      terminus of NS3 (1M-R117 aa) was over-expressed as a recombinant fusion protein
      in a prokaryotic expression system. Biochemical characterization of recombinant
      NS3Nt protein revealed that it forms SDS-resistant dimers and high-order
      oligomers (hexamer and/or octamer) under reducing or non-reducing conditions.
      Coiled-coil motifs are believed to be critical for NS protein oligomerization and
      have potential roles in the formation of viroporin ring/pore either with
      six/eight subunits and this is the first study toward characterization of CCMs in
      NS3 of bluetongue virus.

PMID- 26318175
TI  - In vitro interaction between coxsackievirus B3 VP1 protein and human pleckstrin
      homology domain retinal protein (PHR1).
AB  - Coxsackievirus B3 (CVB3) infection causes central nervous system diseases
      including aseptic meningitis and encephalitis. To understand the mechanism of
      this virus, a yeast two-hybrid system was used to screen cellular proteins from a
      human heart cDNA library. The results revealed that the human Pleckstrin Homology
      Domain Retinal protein (PHR1), a PH domain-containing protein with low expression
      in the heart and high expression in the brain, interacts with CVB3 VP1, a major
      structural protein of CVB3. Yeast mating assays and in vitro
      coimmunoprecipitation verified the interaction between CVB3 VP1 and PHR1. An
      alpha-galactosidase assay indicated that of alpha-galactosidase activity was
      higher in positive clones than in controls suggesting a strong interaction.
      Furthermore, assay of deletion mutants defined the minimal region of PHR1
      required for its interaction with VP1 as amino acids 95-172 and two regions of
      VP1 required for its interaction with PHR1 as amino acids 729-767 and 811-859.
      The results revealed multiple binding sites between PHR1 and CVB3 VP1 and
      suggested that the strong interaction between these two proteins might play an
      important role in central nervous system disease in the human brain.

PMID- 26318176
TI  - Variation in vervet (Chlorocebus aethiops) hair cortisol concentrations reflects
      ecological disturbance by humans.
AB  - Vervet monkeys (Chlorocebus aethiops) often live in close proximity to humans.
      Vervets are known to raid crops, homes and gardens in suburban areas leading to
      human-vervet conflict. In general, primate groups with access to human foods
      experience increased population densities and intra-group aggression. This
      suggests high stress loads for vervets living in environments with high levels of
      human habitat disturbance and close proximity to humans. We tested the hypothesis
      that populations characterized by high levels of human impact are more
      physiologically stressed than low human impact populations, and that this
      increased stress would be reflected in higher concentrations of hair cortisol. We
      predicted that because females would be less likely to engage in high risk
      foraging activities, and hence keep more distance from humans than males, their
      hair cortisol levels should be lower than those in males. We quantified cortisol
      in the hair of wild caught individuals from populations that experienced
      different degrees of human habitat disturbance and differences in access to human
      food. We found that males in high human impact groups had significantly higher
      hair cortisol concentrations than those in low human impact groups, although this
      difference was not observed in female vervets. Human impacts on vervet behavioral
      ecology appear to be a significant source of stress for male animals in
      particular. 

PMID- 26318177
TI  - Recent Advances in Kawasaki Disease - Proceedings of the 3rd Kawasaki Disease
      Summit, Chandigarh, 2014.
AB  - Kawasaki disease (KD) is the most common cause of acquired heart disease in
      children in Japan, North America and Europe. It is now being increasingly
      recognized from the developing countries as well. If not diagnosed and treated in
      time, KD can result in coronary artery abnormalities in approximately 15-25%
      cases. The long-term consequences of these abnormalities may manifest in adults
      as myocardial ischemia and congestive heart failure. Intravenous immunoglobulin
      (IVIg) remains the drug of choice for treatment of KD, but several new agents
      like infliximab, cyclosporine, glucocorticoids and statins are now being
      increasingly used in these patients. While echocardiography has been the
      preferred imaging modality hitherto, CT coronary angiography has emerged as an
      exciting new supplementary option and provides an entirely new dimension to this
      disease. The incidence of KD has shown a progressive increase in several
      countries and it is likely that this disease would impact public health
      programmes in the near future even in the developing countries.

PMID- 26318178
TI  - Comparison of treatment outcomes between nonsurgical and surgical treatment of
      distal radius fracture in elderly: a systematic review and meta-analysis.
AB  - PURPOSE: The best treatment of distal radius fractures (DRFs) in the elderly is
      uncertain. The purpose of this meta-analysis was to compare the outcomes of
      surgical and nonsurgical management of DRFs in persons 65 years of age or older.
      METHODS: Medline, Cochrane, EMBASE, and Google Scholar databases were searched
      until April 27, 2015 using the following search terms: distal radius fracture,
      conservative treatment, nonoperative treatment, nonsurgical treatment, surgical
      treatment, operative, elderly, and older. The primary outcome measure was DASH
      score, and secondary outcomes were functional and radiological assessments. The
      standard difference in post-treatment means was calculated for the outcomes to
      compare the two groups. RESULTS: Of 59 articles identified, eight studies with a
      total of 440 patients in the surgical groups and 449 in the control groups were
      included in the analysis. No significant differences in DASH score, VAS pain
      score, grip strength, wrist extension, pronation, or supination, and ulnar
      deviation were noted between the groups. The nonsurgical group had significantly
      greater wrist flexion, radial deviation, and ulnar variance and less radial
      inclination than the surgical group. CONCLUSIONS: Surgical and nonsurgical
      methods produce similar results in the treatment of DRFS in the elderly, and
      minor objective functional differences did not result an impact on subjective
      function outcome and quality of life.

PMID- 26318179
TI  - Impact of sludge deposition on biodiversity.
AB  - Sludge deposition in the environment is carried out in several countries. It
      encompasses the dispersion of treated or untreated sludge in forests, marsh
      lands, open waters as well as estuarine systems resulting in the gradual
      accumulation of toxins and persistent organic compounds in the environment.
      Studies on the life cycle of compounds from sludge deposition and the
      consequences of deposition are few. Most reports focus rather on treatment
      methods and approaches, legislative aspects as well as analytical evaluations of
      the chemical profiles of sludge. This paper reviews recent as well as some older
      studies on sludge deposition in forests and other ecosystems. From the literature
      covered it can be concluded that sludge deposition induces two detrimental
      effects on the environment: (1) raising of the levels of persistent toxins in
      soil, vegetation and wild life and (2) slow and long-termed biodiversity
      reduction through the fertilizing nutrient pollution operating on the vegetation.
      Since recent studies show that eutrophication of the environment is a major
      threat to global biodiversity supplying additional nutrients through sludge-based
      fertilization seems imprudent. Toxins that accumulate in the vegetation are
      transferred to feeding herbivores and their predators, resulting in a reduced
      long-term survival chance of exposed species. We briefly review current
      legislation for sludge deposition and suggest alternative routes to handling this
      difficult class of waste. 

PMID- 26318180
TI  - Intensive Care Admissions in Pregnancy: Analysis of a Level of Support Scoring
      System.
AB  - OBJECTIVES: Development of a validated triaging system that can be used by
      obstetric providers to identify obstetric patients at risk of developing severe
      morbidity during an admission is urgently required. Maternal Critical Care
      Working Group (MCCWG) recommended a "level of care" strategy that based patient
      acuity needs on number of individual organ systems requiring support. The
      objective of this study was to apply the MCCWG level of support for critical care
      (MCCWG LOC) scoring to pregnant women admitted to an intensive care unit (ICU) to
      predict maternal outcomes and to compare it to the Acute Physiology and Chronic
      Health Evaluation (APACHE) II scoring system. METHODS: In this retrospective
      study, we applied the MCCWG LOC scoring to pregnant women admitted to an ICU at
      the Detroit Medical Center, between January 2006 and December 2010. The MCCWG LOC
      was scored on admission to the ICU, and patients were subsequently divided into
      two groups (Group 1, patients requiring Level 1 and 2 support and Group 2,
      patients requiring level 3a and 3b support) and their outcome variables were
      compared. The MCCWG LOC scores were also compared to APACHE II scoring, an ICU
      scoring system, to test if an alignment of the two systems existed, and if they
      were able to predict outcomes such as death, hospital and intensive care stay.
      RESULTS: Sixty-nine pregnant women (0.25% of deliveries) required admission to
      the ICU and 3 maternal deaths were reported. Sixty-four (92.7%) patients had pre
      existing medical problems. Fifty-eight (84%) of admissions were secondary to a
      medical diagnosis. Mean APACHE II score (p < 0.018) and APACHE II predicted
      mortality rate were significantly higher in Group 2 (p < 0.018). The hospital
      length of stay (LOS) (p < 0.017) and ICU LOS (p < 0.0001) were significantly
      longer in Group 2 as compared to Group 1. Group 2 patients required more
      interventions while in the ICU (p < 0.0001). All the patients who died were
      classified as Group 2. CONCLUSIONS FOR PRACTICE: In a cohort of women requiring
      intensive care admission during pregnancy, MCCWG LOC, a simplified organ system
      based, triaging scoring system, predicted maternal outcomes and correlated with
      APACHE II score. Our data support initiatives for further development and testing
      of global obstetric triaging scoring systems for the purposes of risk
      stratification, monitoring of quality and resource allocation.

PMID- 26318181
TI  - Profound Reversible Hypogammaglobulinemia Caused by Celiac Disease in the Absence
      of Protein Losing Enteropathy.
AB  - When patients with hypogammaglobulinemia are encountered, a vigorous search
      should be undertaken for secondary treatable causes. Here we describe the first
      case of a patient with severe asymptomatic hypogammaglobulinemia where the
      underlying cause was undiagnosed celiac disease. A strict gluten free diet
      resulted in resolution of her mild long-standing abdominal symptoms and
      correction of her hypogammaglobulinemia. There was corresponding improvement in
      her duodenal histology and normalisation of her celiac serology. Protein losing
      enteropathy was unlikely to have been the mechanism of her profound
      hypogammaglobulinemia, as her albumin was within the normal range and she had a
      normal fecal alpha 1 antitrypsin level. Application of the Ameratunga et al.
      (2013) diagnostic criteria was helpful in confirming this patient did not have
      Common Variable Immunodeficiency Disorder (CVID). Celiac disease must now be
      considered in the differential diagnosis of severe hypogammaglobulinemia. There
      should be a low threshold for undertaking celiac serology in patients with
      hypogammaglobulinemia, even if they have minimal symptoms attributable to gut
      disease. 

PMID- 26318183
TI  - Extensive Families of miRNAs and PHAS Loci in Norway Spruce Demonstrate the
      Origins of Complex phasiRNA Networks in Seed Plants.
AB  - In eudicot plants, the miR482/miR2118 superfamily regulates and instigates the
      production of phased secondary small interfering RNAs (siRNAs) from NB-LRR
      (nucleotide binding leucine-rich repeat) genes that encode disease resistance
      proteins. In grasses, this miRNA family triggers siRNA production specifically in
      reproductive tissues from long noncoding RNAs. To understand this functional
      divergence, we examined the small RNA population in the ancient gymnosperm Norway
      spruce (Picea abies). As many as 41 miRNA families in spruce were found to
      trigger phasiRNA (phased, secondary siRNAs) production from diverse PHAS loci,
      with a remarkable 19 miRNA families capable of targeting over 750 NB-LRR genes to
      generate phasiRNAs. miR482/miR2118, encoded in spruce by at least 24 precursor
      loci, targets not only NB-LRR genes to trigger phasiRNA production (as in
      eudicots) but also noncoding PHAS loci, generating phasiRNAs preferentially in
      male or female cones, reminiscent of its role in the grasses. These data suggest
      a dual function of miR482/miR2118 present in gymnosperms that was selectively yet
      divergently retained in flowering plants. A few MIR482/MIR2118 precursors possess
      an extremely long stem-loop structure, one arm of which shows significant
      sequence similarity to spruce NB-LRR genes, suggestive of an evolutionary origin
      from NB-LRR genes through gene duplication. We also characterized an expanded
      miR390-TAS3 (TRANS-ACTING SIRNA GENE 3)-ARF (AUXIN RESPONSIVE FACTOR) pathway,
      comprising 18 TAS3 genes of diverse features. Finally, we annotated spruce miRNAs
      and their targets. Taken together, these data expand our understanding of
      phasiRNA network in plants and the evolution of plant miRNAs, particularly
      miR482/miR2118 and its functional diversification. 

PMID- 26318182
TI  - Roles of Treg/Th17 Cell Imbalance and Neuronal Damage in the Visual Dysfunction
      Observed in Experimental Autoimmune Optic Neuritis Chronologically.
AB  - Optic neuritis associated with multiple sclerosis and its animal model,
      experimental autoimmune optic neuritis (EAON), is characterized by inflammation,
      T cell activation, demyelination, and neuronal damage, which might induce
      permanent vision loss. Elucidating the chronological relationship among the
      features is critical for treatment of demyelinating optic neuritis. EAON was
      induced in C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein
      subcutaneously, and visual function was assessed by flash-visual evoked potential
      (F-VEP) at days 7, 11, 14, 19, 23, 28 post-immunization. Retinal ganglion cell
      (RGC) apoptosis was measured by terminal-deoxynucleotidyl transferase-mediated
      nick-end labeling. Demyelination and axonal damage were verified with myelin
      basic protein (MBP) and beta-amyloid precursor protein staining, respectively.
      Real-time polymerase chain reaction quantified IL-17, IL-1beta, TGF-beta, FoxP3,
      IL-6, and IL-10 mRNA expression in the optic nerve, as well as FoxP3 and IL-17
      staining. Systemic changes of Th17 and Treg cells were tested by flow cytometry
      in spleen. F-VEP latency was prolonged at 11 days and peaked at 23 days
      commensurate with demyelination. However, F-VEP amplitude was reduced at 11 days,
      preceding axon damage, and was exacerbated at 23 days when a peak in RGC
      apoptosis was detected. Th17 cells up-regulated as early as 7 days and peaked at
      11 days, while Treg cells down-regulated inversely compared to Th17 cells change
      as verified by IL-17 and FoxP3 expression; spleen cell samples were slightly
      different, demonstrating marked changed at 14 days. Treg/Th17 cell imbalance in
      the optic nerve precedes and may initiate neuronal damage of axons and RGCs.
      These changes are commensurate with the appearances of visual dysfunction
      reflected in F-VEP and hence may offer a novel therapeutic avenue for vision
      preservation.

PMID- 26318184
TI  - Cis-Regulatory Changes Associated with a Recent Mating System Shift and Floral
      Adaptation in Capsella.
AB  - The selfing syndrome constitutes a suite of floral and reproductive trait changes
      that have evolved repeatedly across many evolutionary lineages in response to the
      shift to selfing. Convergent evolution of the selfing syndrome suggests that
      these changes are adaptive, yet our understanding of the detailed molecular
      genetic basis of the selfing syndrome remains limited. Here, we investigate the
      role of cis-regulatory changes during the recent evolution of the selfing
      syndrome in Capsella rubella, which split from the outcrosser Capsella
      grandiflora less than 200 ka. We assess allele-specific expression (ASE) in
      leaves and flower buds at a total of 18,452 genes in three interspecific F1 C.
      grandiflora x C. rubella hybrids. Using a hierarchical Bayesian approach that
      accounts for technical variation using genomic reads, we find evidence for
      extensive cis-regulatory changes. On average, 44% of the assayed genes show
      evidence of ASE; however, only 6% show strong allelic expression biases. Flower
      buds, but not leaves, show an enrichment of cis-regulatory changes in genomic
      regions responsible for floral and reproductive trait divergence between C.
      rubella and C. grandiflora. We further detected an excess of heterozygous
      transposable element (TE) insertions near genes with ASE, and TE insertions
      targeted by uniquely mapping 24-nt small RNAs were associated with reduced
      expression of nearby genes. Our results suggest that cis-regulatory changes have
      been important during the recent adaptive floral evolution in Capsella and that
      differences in TE dynamics between selfing and outcrossing species could be
      important for rapid regulatory divergence in association with mating system
      shifts. 

PMID- 26318185
TI  - Returning to work after sick leave due to cancer: a 365-day cohort study of
      Japanese cancer survivors.
AB  - PURPOSE: More employees are experiencing a cancer diagnosis during their working
      age years, yet there have been no large-scale Japanese studies investigating sick
      leave due to cancer. We clarified differences in the cumulative partial and full
      return to work (RTW) rates between different cancer types among Japanese cancer
      survivors. METHODS: Data on Japanese employees who experienced an episode of sick
      leave due to clinically certified cancer diagnosed between 1 January 2000 and 31
      December 2011 were obtained from an occupational health register. Subject
      outcomes within the 365-day period following their initial day of sick leave were
      utilized for this study. We investigated the cumulative partial/full and full RTW
      rates by using survival analysis with competing risks and predictors of time to
      RTW by a Fine-Gray proportional hazard regression model. RESULTS: One thousand
      two hundred seventy-eight subjects (1033 males and 245 females) experienced their
      first episode of sick leave due to cancer during the 12-year follow-up period. Of
      the subjects, 47.1% returned to work full time within 6 months of their initial
      day of sick leave absence, and 62.3% by 12 months. The cumulative RTW rate varied
      significantly by cancer type. There were considerable differences in the range of
      cumulative full RTW rates between the two categories ("lower full RTW rate"
      groups ("lung," "hepatic, pancreatic," "esophageal," and "blood" cancer groups)
      vs. "higher full RTW rate" groups ("gastric," "intestinal," "breast," "female
      genital," "male genital," "urinary"): 6.3 to 14.3% vs. 11.4 to 28.3% at 60 days,
      10.6 to 22.4% vs. 27.0 to 50.0% at 120 days, 21.3 to 34.7% vs. 38.5 to 65.4% at
      180 days, 34.3 to 42.9% vs. 66.0 to 79.5% at 365 days). Additionally, older age
      may be associated with a longer time to full RTW. CONCLUSIONS: More than half of
      the subjects returned to work full-time within the 365-day period following their
      initial day of sick leave, with cumulative RTW rates varying by cancer type.
      Older employees may require a longer time to full RTW. IMPLICATIONS OF CANCER
      SURVIVORS: It is very important for companies (especially small- and medium-sized
      companies) to establish and improve their RTW support system for cancer
      survivors, with knowledge that the median time to RTW is expected to be at least
      a few months.

PMID- 26318187
TI  - PTPN22 R620W Polymorphism is Associated with Myasthenia Gravis Risk: A Systematic
      Review and Meta-Analysis.
AB  - BACKGROUND: The association between PTPN22 R620W polymorphism and risk of
      myasthenia gravis (MG) remains controversial. Therefore, we did this meta
      analysis to investigate this association. MATERIAL AND METHODS: We did a
      comprehensive search in PubMed, Medline, Embase, CNKI (China National Knowledge
      Infrastructure), and Wanfang electronic databases to retrieve relevant articles.
      The overall effect was measured by odds ratios (ORs) with its 95% confidence
      intervals (CIs). Statistical analyses were conducted with STATA software.
      RESULTS: Overall, a total of 7 case-control studies with 2802 cases and 3730
      controls were finally included in this review. PTPN22 R620W polymorphism was
      significantly associated with an increased risk of MG (OR=1.57; 95% CI, 1.34
      1.82; I(2)=31%). In the subgroup analysis, thymoma patients were significantly
      associated with risk of MG (OR=1.59; 95% CI, 1.28-1.98; I(2)=0%). However, non
      thymoma patients with this polymorphism did not have increased MG risk (OR=1.36;
      95% CI, 0.86-2.15; I(2)=77%). In addition, PTPN22 R620W polymorphism showed
      increased early-onset myasthenia gravis (EOMG) risk (OR=2.38; 95% CI, 1.52-3.71;
      I(2)=0%). CONCLUSIONS: This meta-analysis shows a significant association between
      PTPN22 R620W polymorphism and MG risk.

PMID- 26318186
TI  - [Urinary tract infections in the elderly].
AB  - Acute infection of the urinary tract is one of the most commonly encountered
      bacterial infections in the frail elderly population and is responsible for
      substantial morbidity and recurrent infections with antibiotic resistance.
      Although generally considered to be self-limiting without treatment or easily
      treated with a short antibiotic regime, urinary tract infections (UTIs) often
      have a dramatic history, associated with incomplete resolution and frequent
      recurrence. The biological complexity of the infections combined with a dramatic
      rise in antibiotic-resistant pathogens highlight the need for an anticipating
      strategy for therapy necessary for a rapid recovery. The first crucial step is
      the classification in asymptomatic bacteriuria or complicated pyelonephritis, on
      which the decision for the intensity of treatment and diagnostic effort is based.
      For the selection of empiric antibiotic therapy, knowledge about the predominant
      uropathogens as well as local resistance patterns is important. In this manner,
      most urinary tract infections in the elderly can be treated without greater
      expense. 

PMID- 26318188
TI  - Susceptibility testing challenges with ceftaroline, MRSA and a 1 mg/L breakpoint.
AB  - OBJECTIVES: A 1 mg/L susceptibility breakpoint for ceftaroline and staphylococci
      is universally agreed; EUCAST counts MIC >1 mg/L as resistant whereas CLSI and
      FDA count 2 mg/L as intermediate and >2 mg/L as resistant. We investigated
      whether routine diagnostic tests reliably distinguish MICs of 1 versus 2 mg/L.
      METHODS: Thirty-five UK laboratories collected Staphylococcus aureus isolates and
      performed tests with 5 MUg (as EUCAST) or 30 MUg (as CLSI) discs and either
      confluent growth on Mueller-Hinton agar (as EUCAST and CLSI) or semi-confluent
      growth on Iso-Sensitest agar (as BSAC). They also ran Etests for MRSA. Reference
      MICs were determined centrally by CLSI and BSAC agar dilution. RESULTS: We
      obtained paired local disc and central MIC results for 1607 S. aureus (33% MRSA).
      EUCAST's zone breakpoint recognized 56% of isolates found resistant in MIC tests,
      but the positive predictive value (PPV) for resistance was 11.0%; corresponding
      proportions by CLSI testing were 28.0% and 13.4%. The BSAC disc method detected
      25% of resistant isolates, with a PPV of 18.2%. Essential agreement, +/-1
      dilution, of local Etests and central agar MICs was >95%, but only 20% of the
      isolates found non-susceptible by agar dilution were found non-susceptible by
      Etest and vice versa. Review for isolates with the modal MIC (0.25 mg/L)
      indicated that the same laboratories reported large or small zones irrespective
      of disc and method, implying systematic bias. CONCLUSIONS: MRSA with ceftaroline
      MICs of 1 and 2 mg/L were poorly discriminated by routine methods. Solutions lie
      in greater standardization, automation or dosages justifying a higher breakpoint.

PMID- 26318189
TI  - Frequent occurrence of oxacillin-susceptible mecA-positive Staphylococcus aureus
      (OS-MRSA) strains in two African countries.
AB  - BACKGROUND: Oxacillin-susceptible mecA-positive Staphylococcus aureus (OS-MRSA)
      isolates have been increasingly reported worldwide, but data regarding the
      African continent have not been available. METHODS: Between 2010 and 2014, 1462
      inpatients and healthcare workers were screened for MRSA nasal carriage in Sao
      Tome and Principe (STP) and Angola, two Portuguese-speaking African countries
      (PALOP countries). We determined the presence of the mecA gene and the
      antimicrobial susceptibility profiles of the isolates. OS-MRSA clonal lineages
      were identified as well as the presence of virulence determinants, including
      Panton-Valentine leucocidin (PVL). RESULTS: Out of 164 S. aureus hospital
      isolates tested, 29 (17.7%) were mecA positive, but susceptible to oxacillin,
      showing oxacillin MICs <=3 mg/L. All OS-MRSA isolates were resistant to cefoxitin
      and most of them were also resistant to at least two antimicrobials other than
      beta-lactams. The 29 OS-MRSA were distributed into two major clonal lineages: (i)
      PFGE type B-ST88-SCCmec IVa, associated with spa types
      t186/t325/t786/t1814/t1951, detected in Angola (n = 5) and STP (n = 10); and (ii)
      PFGE type C-t451/t648-ST8-SCCmec V, exclusively found in STP (n = 9). OS-MRSA
      showed at least two virulence determinants. PVL was detected in an isolate
      recovered in STP. CONCLUSIONS: We describe a high prevalence of OS-MRSA among S.
      aureus strains recovered in two African countries. OS-MRSA in PALOP countries
      were mainly associated with ST88 and ST8, two prevalent MRSA clonal types in
      these countries. If direct testing for mecA is not available, cefoxitin
      susceptibility testing is highly recommended to avoid the misidentification of OS
      MRSA.

PMID- 26318190
TI  - New pharmacokinetic/pharmacodynamic studies of systemically administered colistin
      against Pseudomonas aeruginosa and Acinetobacter baumannii in mouse thigh and
      lung infection models: smaller response in lung infection.
AB  - OBJECTIVES: This study investigated the exposure-response relationships between
      unbound colistin in plasma and antibacterial activity in mouse thigh and lung
      infections. METHODS: Dose fractionation studies (subcutaneous colistin sulphate
      at 1.25-160 mg/kg/day) were conducted in neutropenic mice in which infection
      (three strains of Pseudomonas aeruginosa and three strains of Acinetobacter
      baumannii) had been produced by intramuscular thigh injection or aerosol lung
      delivery. Bacterial burden was measured at 24 h after initiation of colistin
      treatment. Plasma protein binding was measured by rapid equilibrium dialysis and
      ultracentrifugation. The inhibitory sigmoid dose-effect model and non-linear
      least squares regression were employed to determine the relationship between
      exposure to unbound colistin and efficacy. RESULTS: Plasma binding of colistin
      was constant over the concentration range ~2-50 mg/L. The average +/- SD
      percentage bound for all concentrations was 92.9 +/- 3.3% by ultracentrifugation
      and 90.4 +/- 1.1% by equilibrium dialysis. In the thigh model, across all six
      strains the antibacterial effect of colistin was well correlated with fAUC/MIC
      (R(2) = 0.82-0.94 for P. aeruginosa and R(2) = 0.84-0.95 for A. baumannii).
      Target values of fAUC/MIC for 2 log10 kill were 7.4-13.7 for P. aeruginosa and
      7.4-17.6 for A. baumannii. In the lung model, for only two strains of P.
      aeruginosa and one strain of A. baumannii was it possible to achieve 2 log10 kill
      (fAUC/MIC target values 36.8-105), even at the highest colistin dose tolerated by
      mice. This dose was not able to achieve bacteriostasis for the other two strains
      of A. baumannii. CONCLUSIONS: Colistin was substantially less effective in lung
      infection. The pharmacokinetic/pharmacodynamic target values will assist in the
      design of optimized dosage regimens.

PMID- 26318192
TI  - Comment on: Acquired macrolide resistance genes in Haemophilus influenzae?

PMID- 26318191
TI  - Phylogenetic lineages, clones and beta-lactamases in an international collection
      of Klebsiella oxytoca isolates non-susceptible to expanded-spectrum
      cephalosporins.
AB  - OBJECTIVES: The objective of this study was to examine Klebsiella oxytoca clonal
      and phylogenetic diversity, based on an international collection of carriage
      isolates non-susceptible to expanded-spectrum cephalosporins (ESCs). METHODS: The
      study material comprised 68 rectal carriage K. oxytoca isolates non-susceptible
      to ESCs recovered in 2008-11 from patients in 14 hospitals across Europe and
      Israel. ESC resistance was tested phenotypically; genes encoding ESBLs, AmpC
      cephalosporinases and carbapenemases were amplified and sequenced. The isolates
      were typed by PFGE and MLST, followed by sequencing of blaOXY genes. RESULTS:
      MLST and PFGE distinguished 34 STs and 47 pulsotypes among the isolates,
      respectively. Six STs were split into several pulsotypes each. Five STs were more
      prevalent (n = 2-9) and occurred in several countries each, including ST2, ST9
      and ST141, which belong to a growing international clonal complex (CC), CC2. Four
      phylogenetic lineages were distinguished, each with another type of chromosomal
      OXY-type beta-lactamase. Three of these, with OXY-1/-5, OXY-2 types and OXY-4,
      corresponded to previously described phylogroups KoI, KoII and KoIV,
      respectively. A single isolate from Israel represented a distinct lineage with a
      newly defined OXY-7 type. The phylogroups showed interesting differences in
      mechanisms of ESC resistance; KoI strains rarely overexpressed the OXY enzymes
      but commonly produced ESBLs, whereas KoII strains often were OXY hyperproducers
      and carried ESBLs much less frequently. AmpCs (DHA-1) and carbapenemases (VIM-1)
      occurred sporadically. CONCLUSIONS: The study confirmed the high genetic
      diversity of the collection of K. oxytoca ESC-non-susceptible isolates, composed
      of phylogroups with distinct types of OXY-type beta-lactamases, and revealed some
      STs of broad geographical distribution.

PMID- 26318193
TI  - Genetic diversity of blaTEM alleles, antimicrobial susceptibility and molecular
      epidemiological characteristics of penicillinase-producing Neisseria gonorrhoeae
      from England and Wales.
AB  - OBJECTIVES: The objective of this study was to investigate the genetic diversity
      of blaTEM alleles, antimicrobial susceptibility and molecular epidemiological
      characteristics of penicillinase-producing Neisseria gonorrhoeae (PPNG) isolates
      collected in 2012 from England and Wales. METHODS: PPNG isolates were from the
      2012 Gonococcal Resistance to Antimicrobial Surveillance Programme (GRASP). Their
      susceptibility to seven antimicrobials was determined using agar dilution
      methodology. beta-Lactamase production was detected using a nitrocefin test. beta
      Lactamase plasmid types were determined and blaTEM genes were sequenced. Isolates
      were also typed by N. gonorrhoeae multi-antigen sequence typing (NG-MAST).
      RESULTS: Seventy-three PPNG isolates were identified in the 2012 GRASP collection
      (4.6%, 73/1603). Three different blaTEM alleles were identified, encoding three
      TEM amino acid sequences: TEM-1 (53%), TEM-1 with a P14S substitution (19%) and
      TEM-135 (27%). The blaTEM-135 allele was present in nine different NG-MAST types
      and was found mostly on Asian (60%) and Toronto/Rio (35%) plasmids. By contrast,
      most TEM-1-encoding plasmids were African (98%). All the TEM-135 isolates
      displayed high-level ciprofloxacin and tetracycline resistance. CONCLUSIONS: The
      high proportion of blaTEM-135 alleles (27%) demonstrates that this variant is
      circulating within several gonococcal lineages. Only a single specific mutation
      near the beta-lactamase active site could result in TEM-135 evolving into an
      ESBL. This is concerning particularly because the TEM-135 isolates were
      associated with high-level ciprofloxacin and tetracycline resistance. It is
      encouraging that no further TEM alleles were detected in this gonococcal
      population; however, vigilance is vital as an ESBL in N. gonorrhoeae would render
      the last remaining option for monotherapy, ceftriaxone, useless.

PMID- 26318194
TI  - Genetic environment of metallo-beta-lactamase genes in Pseudomonas aeruginosa
      isolates from the UK.
AB  - OBJECTIVES: We sought to characterize the genetic environment of blaVIM and
      blaIMP genes in Pseudomonas aeruginosa isolates from the UK; these included
      members of six previously described prevalent complexes, A-F, which correspond to
      international 'high-risk clones', along with diverse strains. METHODS: Metallo
      beta-lactamase (MBL)-encoding class 1 integrons were amplified by PCR from 218 P.
      aeruginosa isolates producing VIM-type (n = 196) or IMP-type (n = 22) enzymes,
      referred from UK hospital laboratories between 2003 and 2012. The variable
      regions of selected integrons were sequenced using a primer walking method.
      RESULTS: One-hundred-and-nineteen isolates had an MBL-encoding integron with the
      3' conserved sequence (3'CS), 65 had Tn5090-like 3' regions and 17 had the sul1
      gene, but lacked the qacEDelta1 gene; the 3' region could not be amplified using
      any primer combinations for the remaining 17 isolates. Six integron profiles were
      each seen in more than five isolates. Predominant integron types were seen
      amongst isolates belonging to STs 111, 233, 654/964 and 773 (complexes A, C, D
      and F, respectively), whereas diverse integron profiles were seen in isolates
      belonging to ST235 (complex B) and ST357 (complex E). CONCLUSIONS: In UK P.
      aeruginosa isolates, MBL genes occur in diverse class 1 integron structures,
      though commonly with 3' regions containing the classical 3'CS or Tn5090-like
      regions. Four of the six main clonal complexes, referred from multiple
      laboratories, carried a predominant integron type, whereas the remaining two had
      more diverse types.

PMID- 26318195
TI  - Tighter glycemic control is associated with ADL physical dependency losses in
      older patients using sulfonylureas or mitiglinides: Results from the DIMORA
      study.
AB  - BACKGROUND: There is growing evidence that tight glycemic control may be more
      harmful than beneficial in older persons with Type 2 diabetes (T2DM). It remains
      controversial if tight glycemic control (lower glycated hemoglobin A1c (A1c)) is
      associated with functional impairments in older frail patients with T2DM. We
      explored associations between A1c and losses in Activities of Daily Living (ADLs)
      in diabetic nursing home (NH) patients and tested for differences according to
      anti-diabetic treatment: diet, anti-diabetic oral drug (AOD), insulin, combined
      insulin+AOD. METHODS: We conducted a cross-sectional study on 1845 older NH
      patients with T2DM from 150 sites across Italy. Complete evaluations on ADLs,
      glycemic control, anti-diabetic treatments, comorbidities, and clinical data were
      recorded. ANOVA was applied to compare clinical characteristics across A1c
      tertiles. Multivariate regression models evaluated associations between A1c and
      ADL losses. RESULTS: Patients had a mean age [SD]=82 [8] years; BMI=25.5 kg/m(2)
      [4.7]; Fasting Plasma Glucose (FPG)=7.4 [3.0] mmol/l; Post-prandial glucose
      (PPG)=10.3 [3.6] mmol/l; A1c=7.0% (54 mmol/mol), ADL losses=3.7 [1.8]. Compared
      to higher A1c tertiles, patients in the lower tertile had greater ADL losses,
      were more likely to use AODs, while less likely to use insulin or insulin+AOD.
      After adjusting for multiple confounders, impairments in ADLs were associated
      with tighter A1c levels (B=-0.014; p=0.002). Regression models according to anti
      diabetic treatment showed that tighter A1c levels continued as independent
      determinants of ADL losses in patients using AODs (B=-0.023; p=0.001),
      particularly in those using sulfonylureas (B=-0.043; p<0.001) or mitiglinides (B=
      0.044; p=0.050). CONCLUSIONS: Tighter glycemic control was associated with ADL
      physical dependency losses, especially in those using sulfonylureas and
      mitiglinides.

PMID- 26318197
TI  - Artesunate alleviates hepatic fibrosis induced by multiple pathogenic factors and
      inflammation through the inhibition of LPS/TLR4/NF-kappaB signaling pathway in
      rats.
AB  - The current study was performed in order to explore the effect of artesunate
      (Art) on experimental hepatic fibrosis and the potential mechanism involved. Art,
      a water-soluble hemisuccinate derivative of artemisinin extracted from the
      Chinese herb Artemisia Annua, is a safe and effective antimalarial drug. Hepatic
      fibrosis was induced in SD rats by multiple pathogenic factors. Rats were treated
      concurrently with Art (28.8 mg/kg) given daily by oral gavage for 6 or 8 weeks to
      evaluate its protective effects. Our data demonstrated that Art treatment
      obviously attenuated hepatic fibrosis, characterized by less inflammatory
      infiltration and accumulation of extracellular matrix (ECM). Art remarkably
      decreased endotoxin, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6
      (IL-6) levels as well. Art significantly downregulated protein and mRNA
      expression of alpha-smooth muscle actin (alpha-SMA), toll-like receptors 4
      (TLR4), myeloid differentiation factor 88 (MyD88) and transforming growth factor
      beta 1 (TGF-beta1). Art also significantly inhibited the nuclear transcription
      factor kappa B p65 (NF-kappaB p65) translocation into the nucleus. In addition,
      there were no remarkable differences between the N group and the NA group. In
      conclusion, we found that Art could alleviate hepatic fibrosis induced by
      multiple pathogenic factors and inflammation through the inhibition of
      LPS/TLR4/NF-kappaB signaling pathway in rats, suggesting that Art may be a
      potential candidate for the therapy of hepatic fibrosis.

PMID- 26318198
TI  - Effects of ONO-6950, a novel dual cysteinyl leukotriene 1 and 2 receptors
      antagonist, in a guinea pig model of asthma.
AB  - We assessed in this study the anti-asthmatic effects of ONO-6950, a novel
      cysteinyl leukotriene 1 (CysLT1) and 2 (CysLT2) receptors dual antagonist, in
      normal and S-hexyl glutathione (S-hexyl GSH)-treated guinea pigs, and compared
      these effects to those of montelukast, a CysLT1 selective receptor antagonist.
      Treatment with S-hexyl GSH reduced animals LTC4 metabolism, allowing practical
      evaluation of CysLT2 receptor-mediated airway response. ONO-6950 antagonized
      intracellular calcium signaling via human and guinea pig CysLT1 and CysLT2
      receptors with IC50 values of 1.7 and 25 nM, respectively (human receptors) and
      6.3 and 8.2 nM, respectively (guinea pig receptors). In normal guinea pigs, both
      ONO-6950 (1 or 0.3 mg/kg, p.o.) and the CysLT1 receptor antagonist montelukast
      (0.3 or 0.1 mg/kg, p.o.) fully attenuated CysLT1-mediated bronchoconstriction and
      airway vascular hyperpermeability induced by LTD4. On the other hand, in S-hexyl
      GSH-treated guinea pigs ONO-6950 at 3 mg/kg, p.o. or more almost completely
      inhibited bronchoconstriction and airway vascular hyperpermeability elicited by
      LTC4, while montelukast showed only partial or negligible inhibition of these
      airway responses. In ovalbumin sensitized guinea pigs, treatment with S-hexyl GSH
      on top of pyrilamine and indomethacin rendered antigen-induced
      bronchoconstriction sensitive to both CysLT1 and CysLT2 receptor antagonists. ONO
      6950 strongly inhibited this asthmatic response to the level attained by
      combination therapy with montelukast and BayCysLT2RA, a selective CysLT2 receptor
      antagonist. These results clearly demonstrate that ONO-6950 is an orally active
      dual CysLT1/LT2 receptor antagonist that may provide a novel therapeutic option
      for patients with asthma.

PMID- 26318199
TI  - DFT study of 1-butyl-3-methylimidazolium salicylate: a third-generation ionic
      liquid.
AB  - A detailed theoretical investigation of the third-generation ionic liquid (IL) 1
      butyl-3-methylimidazolium salicylate ([BMIM][Sal]), performed within the
      framework of density functional theory (DFT), is presented in this paper. The
      B3LYP-D3, M06-2X, and M06-2X-D3 functionals were used to obtain the equilibrium
      geometries of the two ions [BMIM](+) and [Sal](-). It is shown that the
      equilibrium ion geometries obtained with the dispersion-corrected B3LYP
      functional are very close to the ion geometries obtained with the M06-2X and M06
      2X-D3 functionals. Global reactivity was assessed using molecular orbital theory
      and quantum molecular descriptors. Molecular electrostatic potential (MEP)
      surfaces and average local ionization energy (ALIE) surfaces were created in
      order to elucidate the charge distribution and reactivity of the investigated IL.
      Ion-pair binding energies were calculated with all three functionals, and the
      results confirmed the presence of a strong electrostatic interaction between the
      ions, while further insight into the interactions between the two ions was
      obtained by analyzing noncovalent interactions based on the reduced density
      gradient (RDG) surface, which revealed a total of nine interactions between the
      ions. Finally, the aromaticity of each ion was investigated by calculating the
      nucleus-independent chemical shift (NICS) parameter, which indicated that
      significant changes in the charge delocalization on each ion occur when the two
      ions interact.

PMID- 26318196
TI  - Pathobiological implications of mucin glycans in cancer: Sweet poison and novel
      targets.
AB  - Mucins are large glycoproteins expressed on the epithelia that provide a
      protective barrier against harsh insults from toxins and pathogenic microbes.
      These glycoproteins are classified primarily as being secreted and membrane
      bound; both forms are involved in pathophysiological functions including
      inflammation and cancer. The high molecular weight of mucins is attributed to
      their large polypeptide backbone that is extensively covered by glycan moieties
      that modulate the function of mucins and, hence, play an important role in
      physiological functions. Deregulation of glycosylation machinery during malignant
      transformation results in altered mucin glycosylation. This review describes the
      functional implications and pathobiological significance of altered mucin
      glycosylation in cancer. Further, this review delineates various factors such as
      glycosyltransferases and tumor microenvironment that contribute to dysregulation
      of mucin glycosylation during cancer. Finally, this review discusses the scope of
      mucin glycan epitopes as potential diagnostic and therapeutic targets. 

PMID- 26318200
TI  - Critical test of some computational methods for prediction of NMR 1H and 13C
      chemical shifts.
AB  - Performance of 18 DFT functionals (B1B95, B3LYP, B3PW91, B97D, BHandHLYP, BMK,
      CAM-B3LYP, HSEh1PBE, M06-L, mPW1PW91, O3LYP, OLYP, OPBE, PBE1PBE, tHCTHhyb,
      TPSSh, wB97xD, VSXC) in combinations with six basis sets (cc-pVDZ, aug-cc-pVDZ,
      cc-pVTZ, aug-cc-pVTZ, IGLO-II, and IGLO-III) and three methods for calculating
      magnetic shieldings (GIAO, CSGT, IGAIM) was tested for predicting (1)H and (13)C
      chemical shifts for 25 organic compounds, for altogether 86 H and 88 C atoms.
      Proton shifts varied between 1.03 ppm to 12.00 ppm and carbon shifts between 7.87
      ppm to 209.28 ppm. It was found that the best method for calculating (13)C shifts
      is PBE1PBE/aug-cc-pVDZ with CSGT or IGAIM approaches (mae = 1.66 ppm), for (1)H
      the best results were obtained with HSEh1PBE, mPW1PW91, PBE1PBE, CAM-B3LYP, and
      B3PW91 functionals with cc-pVTZ basis set and with CSGT or IGAIM approaches (mae
      = 0.28 ppm). We found that often larger basis sets do not give better results for
      chemical shifts. The best basis sets for calculating (1)H and (13)C chemical
      shifts were cc-pVTZ and aug-cc-pVDZ, respectively. CSGT and IGAIM NMR approaches
      can perform really well and are in most cases better than popular GIAO approach.

PMID- 26318201
TI  - Theoretical insights into the structures and mechanical properties of HMX/NQ
      cocrystal explosives and their complexes, and the influence of molecular ratios
      on their bonding energies.
AB  - Molecular dynamics (MD) methods were employed to study the binding energies and
      mechanical properties of selected crystal planes of 1,3,5,7-tetranitro-1,3,5,7
      tetrazacyclooctane (HMX)/nitroguanidine (NQ) cocrystals at different molecular
      molar ratios. The densities and detonation velocities of the cocrystals at
      different molar ratios were estimated. The intermolecular interaction and bond
      dissociation energy (BDE) of the N-NO2 bond in the HMX:NQ (1:1) complex were
      calculated using the B3LYP, MP2(full) and M06-2X methods with the 6-311++G(d,p)
      and 6-311++G(2df,2p) basis sets. The results indicated that the HMX/NQ cocrystal
      prefers cocrystalizing in a 1:1 molar ratio, and the cocrystallization is
      dominated by the (0 2 0) and (1 0 0) facets. The K, G, and E values of the ratio
      of 1:1 are smaller than those of the other ratios, and the 1:1 cocrystal has the
      best ductility. The N-NO2 bond becomes stronger upon the formation of the
      intermolecular H-bonding interaction and the sensitivity of HMX decreases in the
      cocrystal. This sensitivity change in the HMX/NQ cocrystal originates not only
      from the formation of the intermolecular interaction but also from the increment
      of the BDE of N-NO2 bond in comparison with isolated HMX. The HMX/NQ (1:1)
      cocrystal exhibits good detonation performance. Reduced density gradient (RDG)
      reveals the nature of cocrystallization. Analysis of the surface electrostatic
      potential further confirmed that the sensitivity decreases in complex (or
      cocrystal) in comparison with that in isolated HMX.

PMID- 26318202
TI  - The "butterfly diagram": A gait marker for neurological and cerebellar impairment
      in people with multiple sclerosis.
AB  - People with multiple sclerosis (PwMS) frequently experience walking and balance
      impairments. In our previous report, we demonstrated that spatio-temporal gait
      parameters, collected by the Zebris FDM-T instrumented treadmill (Zebris Medical
      GmbH, Germany), serve as valid markers of neurological impairment in the MS
      population. In the current study, we focused on a unique outcome statistic of the
      instrumented treadmill, the "butterfly" diagram which reflects the variability of
      the center of pressure trajectory during walking. Therefore, the aim of the study
      was to examine the relationship between parameters related to the gait butterfly
      diagram and the level of neurological impairment in PwMS. Specifically we
      examined whether the gait butterfly parameters can differentiate between MS
      patients with normal cerebellar function and those suffering from ataxia.
      Demographic, neurological and gait parameters were collected from 341 PwMS, 213
      women, aged 42.3 (S.D.=13.8). MS participants with ataxia demonstrated higher
      scores relating to the butterfly gait variability parameters compared to PwMS
      with normal or slightly abnormal cerebellar function. According to the results of
      the binary regression analysis, gait variability in the ant-post direction was
      found to explain 18.1% of the variance related to cerebellar function;
      R(2)=0.181, chi(2)(1)=67.852, P<0.001. Measurements derived from the butterfly
      diagram are proper estimators for important neurological functions in PwMS and
      should be considered in order to improve diagnosis and assessment of the MS
      population. 

PMID- 26318203
TI  - Venous thromboembolism prevention during the acute phase of intracerebral
      hemorrhage.
AB  - BACKGROUND: Although knowledge of intracerebral hemorrhage (ICH) continues to
      evolve, it is still a major cause of morbidity and mortality worldwide. Venous
      thromboembolism (VTE) events, including deep vein thrombosis (DVT) and pulmonary
      embolism (PE), are common and preventable complications of ICH. On the basis of
      the current systematic review and guidelines, the optimal prophylactic treatment
      remains unclear. SUMMARY: In this review, we used the existing literature to
      provide an overview of the prevalence, treatment, guidelines, and worldwide trend
      and future issues regarding VTE events after ICH. KEY MESSAGES: Briefly, VTE
      events are common, with severe complications following ICH. Clinicians should be
      familiar with the current guidelines and trials to identify the optimal treatment
      for every patient's unique condition.

PMID- 26318204
TI  - Brain FDG-PET reflecting clinical course of depression induced by systemic lupus
      erythematosus: Two case reports.

PMID- 26318205
TI  - Tissue Mercury Concentrations and Survival of Tree Swallow Embryos, Nestlings and
      Young Adult Females on a Contaminated Site.
AB  - Tree swallows nesting on mercury-contaminated sites along the South River in
      Virginia, USA were monitored for reproductive success. The bodies of nestlings
      found deceased in their nest boxes were collected, along with blood and feather
      samples from the adult parents and surviving siblings. We also measured hatching
      and fledging success of the clutches and the annual recapture rate of adults. We
      found that the body feathers of deceased nestlings contained significantly higher
      concentrations of mercury (12.89 +/- 8.42 MUg/g, n = 15) than those of nestlings
      that survived to fledge (7.41 +/- 4.79 MUg/g, n = 15). However, mothers of more
      successful clutches (>75 % hatching) did not differ in mercury concentrations
      from females with less successful clutches (<50 % hatching). Additionally, adult
      females breeding for the first time that returned to breed the following year did
      not differ in blood mercury from females of the same age that bred once but never
      returned. Our results suggest that mercury had its greatest effect on these
      songbirds during the nestling stage, whereas for embryos or first-time breeding
      females, other factors likely played larger roles in mortality. 

PMID- 26318206
TI  - Multi-locus phylogeny and divergence time estimates of Enallagma damselflies
      (Odonata: Coenagrionidae).
AB  - Reconstructing evolutionary patterns of species and populations provides a
      framework for asking questions about the impacts of climate change. Here we use a
      multilocus dataset to estimate gene trees under maximum likelihood and Bayesian
      models to obtain a robust estimate of relationships for a genus of North American
      damselflies, Enallagma. Using a relaxed molecular clock, we estimate the
      divergence times for this group. Furthermore, to account for the fact that gene
      tree analyses can overestimate ages of population divergences, we use a multi
      population coalescent model to gain a more accurate estimate of divergence times.
      We also infer diversification rates using a method that allows for variation in
      diversification rate through time and among lineages. Our results reveal a
      complex evolutionary history of Enallagma, in which divergence events both
      predate and occur during Pleistocene climate fluctuations. There is also evidence
      of diversification rate heterogeneity across the tree. These divergence time
      estimates provide a foundation for addressing the relative significance of
      historical climatic events in the diversification of this genus.

PMID- 26318207
TI  - Seven-day ethanol administration influence on the rat brain histaminergic
      neurons.
AB  - The purpose of the study is to clarify the effect of 7 days of ethanol
      administration upon brain histaminergic neurons in rats. Male Wistar rats were
      injected intraperitoneally (i.p.) with 20% ethanol/saline (0.85% NaCl) daily,
      over 7 days, whereas control rats were given saline. The animals were decapitated
      24 h after the 7th injection and samples of hypothalamus were prepared for light
      and electron microscopy, accompanied by morphometry to examine the histaminergic
      neurons. It was found that ethanol administration gradually decreased the
      duration of alcohol-induced sleep and decreased the total amount of histaminergic
      neurons and the amount of histologically normal neurons, but increased the amount
      of hypochromic neurons and shadow cells. The histaminergic neuron bodies and
      nuclei decreased in size. The ultrastructural changes in histaminergic neurons
      demonstrated activation of their nuclear apparatus, both destruction or
      hypertrophy and hyperplasia of organelles, especially lysosomes. The
      histochemical examination revealed the activation of lactate dehydrogenase and
      acid phosphatase, and inhibition of NADH-, NADPhH, and succinate dehydrogenases.
      Following 7 days of ethanol administration, histaminergic neurons exhibit the
      structural signs of hyperactivity, which can be related to neuronal adaptation to
      the actions of ethanol, and increased behavioral tolerance to ethanol. 

PMID- 26318208
TI  - The neuronal identity bias behind neocortical GABAergic plasticity.
AB  - In the neocortex, different types of excitatory and inhibitory neurons connect to
      one another following a detailed blueprint, defining functionally-distinct
      subnetworks, whose activity and modulation underlie complex cognitive functions.
      We review the cell-autonomous plasticity of perisomatic inhibition onto principal
      excitatory neurons. We propose that the tendency of different cortical layers to
      exhibit depression or potentiation of perisomatic inhibition is dictated by the
      specific identities of principal neurons (PNs). These are mainly defined by their
      projection targets and by their preference to be innervated by specific
      perisomatic-targeting basket cell types. Therefore, principal neurons responsible
      for relaying information to subcortical nuclei are differentially inhibited and
      show specific forms of plasticity compared to other PNs that are specialized in
      more associative functions. 

PMID- 26318209
TI  - Food deserts or food swamps?: A mixed-methods study of local food environments in
      a Mexican city.
AB  - Differential access to healthy foods has been hypothesized to contribute to
      disparities in eating behaviors and health outcomes. While food deserts have been
      researched extensively in developed Anglophone countries, evidence from low- and
      middle-income countries is still scarce. In Mexico, prevalence of obesity is
      among the highest worldwide. As obesity has increased nationally and become a
      widespread public health issue, it is becoming concentrated in the low-income
      population. This mixed-methods study uses a multidimensional approach to analyze
      food environments in a low-, middle-, and high-income community in a Mexican
      city. The study advances understanding of the role that food environments may
      play in shaping eating patterns by analyzing the density and proximity of food
      outlet types as well as the variety, quantity, quality, pricing, and promotion of
      different foods. These measures are combined with in-depth qualitative research
      with families in the communities, including photo elicitation, to assess
      perceptions of food access. The central aims of the research were to evaluate
      physical and economic access and exposure to healthy and unhealthy foods in
      communities of differing socioeconomic status as well as participants' subjective
      perceptions of such access and exposure. The findings suggest a need to reach
      beyond a narrow focus on food store types and the distance from residence to
      grocery stores when analyzing food access. Results show that excessive access and
      exposure to unhealthy foods and drinks, or "food swamps," may be a greater
      concern than food deserts for obesity-prevention policy in Mexico. 

PMID- 26318210
TI  - Citing conduct, individualizing symptoms: Accomplishing autism diagnosis in
      clinical case conferences.
AB  - In this paper, I examine how clinicians at a clinic for developmental
      disabilities in the United States determine whether children being evaluated for
      autism spectrum disorder (ASD) showed symptoms of that condition. Drawing on a
      convenience sample of 61 audio and video recorded case conferences from two time
      periods (1985 and 2011-15), and combining Conversation Analysis with insights
      from Actor Network Theory, I find that clinicians describe (via a
      representational practice called "citation") children's conduct in ways that
      advance diagnostic claims. More specifically, they portray key actants in the
      assessment process in patterned ways: the test instrument is represented as a
      neutral tool of measurement, the clinician as administrator and instructor; and
      the child as the focal figure whose conduct is made to appear independent of the
      other participants and suggestive of diagnostic symptoms. These tacit
      representational conventions conform to and reproduce the assumptions of
      standardized testing, according to which clinicians and tests are to be neutral
      arbiters of the child's abilities, and thereby provide for objective, warrantable
      findings. At the same time, however, by designing representations around the
      child's symptomatic conduct in this way, clinicians may minimize or elide their
      own contributions, and those of the test instrument, to the child's performance,
      and thereby make the child alone appear responsible for what are, in fact,
      interactionally-occasioned behaviors. 

PMID- 26318211
TI  - The value of frameworks as knowledge translation mechanisms to guide community
      participation practice in Ontario CHCs.
AB  - The community participation literature has produced numerous frameworks to guide
      practice and evaluation of community participation strategies in the health
      sector. These frameworks are useful starting points for differentiating the
      approaches for involving people in planning and decision-making for health
      services, but have been critiqued for being too generic and ignoring that
      community participation is highly contextual and situational. Health service
      organizations across Canada and internationally have begun to respond to address
      this limitation by developing more context-specific community participation
      frameworks; however, such frameworks do not exist for Ontario Community Health
      Centres (CHCs)-local primary health care organizations with a mandate to engage
      marginalized groups in planning and decision-making for health services. We
      conducted a series of focus groups with staff members from four Ontario CHCs to:
      (1) examine the factors that would influence their use of a generic framework for
      community participation with marginalized populations; and (2) improve the
      "context-specificity" of this framework, to enhance its relevance to CHCs.
      Participants described the difficulty of organizing the contextual, multi-faceted
      and situational process of community participation that they experienced with
      marginalized populations into a single framework, which led them to question the
      value of using frameworks as a resource for guiding the design, implementation
      and evaluation of their community participation initiatives. Instead,
      participants revealed that tacit knowledge, in the form of professional and
      personal experience and local knowledge of a marginalized population, had a
      greater influence on guiding participation activities in Ontario CHCs. Our
      findings suggest that tacit knowledge is an essential feature of community
      participation practice and requires further exploration regarding its role in the
      community participation field. 

PMID- 26318212
TI  - The Biobehavioral Family Model: Close relationships and allostatic load.
AB  - RATIONALE: This study tested the inclusion of allostatic load as an expansion of
      the biobehavioral reactivity measurement in the Biobehavioral Family Model
      (BBFM). The BBFM is a biopsychosocial approach to health which proposes
      biobehavioral reactivity (anxiety and depression) mediates the relationship
      between family emotional climate and disease activity. METHODS: Data for this
      study included a subsample of n = 1255 single and married, English-speaking adult
      participants (57% female, M age = 56 years) from the National Survey of Midlife
      Development in the United States (MIDUS II), a nationally representative
      epidemiological study of health and aging in the United States. Participants
      completed self-reported measures of family and marital functioning, anxiety and
      depression (biobehavioral reactivity), number of chronic health conditions,
      number of prescribed medications, and a biological protocol in which the
      following indices were obtained: cardiovascular functioning, sympathetic and
      parasympathetic nervous system activity, hypothalamic pituitary adrenal axis
      activity, inflammation, lipid/fat metabolism, and glucose metabolism. RESULTS:
      Structural equation modeling indicated good fit of the data to the hypothesized
      family model (chi (2) = 125.13 p = .00, SRMR = .03, CFI = .96, TLI = .94, RMSEA =
      .04) and hypothesized couple model (chi(2) = 132.67, p = .00, SRMR = .04, CFI =
      .95, TLI = .93, RMSEA = .04). Negative family interactions predicted
      biobehavioral reactivity for anxiety and depression and allostatic load; however
      couple interactions predicted only depression and anxiety measures of
      biobehavioral reactivity. CONCLUSION: Findings suggest the importance of
      incorporating physiological data in measuring biobehavioral reactivity as a
      predicting factor in the overall BBFM model.

PMID- 26318213
TI  - Social mobility and health in European countries: Does welfare regime type
      matter?
AB  - Health inequalities pose an important public health challenge in European
      countries, for which increased social mobility has been suggested as a cause. We
      sought to describe how the relationship between health inequalities and social
      mobility varies among welfare regime types in the European region. Data from six
      rounds of the European Social Survey was analyzed using multilevel statistical
      techniques, stratified by welfare regime type, including 237,535 individuals from
      136 countries. Social mobility among individuals was defined according to the
      discrepancy between parental and offspring educational attainment. For each
      welfare regime type, the association between social mobility and self-rated
      health was examined using odds ratios and risk differences, controlling for
      parental education. Upwardly mobile individuals had between 23 and 44% lower odds
      of reporting bad or very bad self-rated health when compared to those who
      remained stable. On an absolute scale, former USSR countries showed the biggest
      and only significant differences for upward movement, while Scandinavian
      countries showed the smallest. Downward social mobility tended to be associated
      with worse health, but the results were less consistent. Upward social mobility
      is associated with worse health in all European welfare regime types. However, in
      Scandinavian countries the association of upward mobility was smaller, suggesting
      that the Nordic model is more effective in mitigating the impact of social
      mobility on health and/or of health on mobility. 

PMID- 26318214
TI  - Trust, reciprocity and collective action to fight antibiotic resistance. An
      experimental approach.
AB  - Antibiotic resistance is a collective action dilemma. Individuals may request
      antibiotics, but an overall reduction in use is necessary to limit resistance. A
      reoccurring theoretical claim is that social capital increase cooperation in
      social dilemmas. The aim of this paper is to investigate the link between
      generalized trust and reciprocity and the willingness to postpone antibiotic
      treatment in order to limit overuse in a scenario-based study. A between-subject
      scenario experimental approach with hypothetical scenarios was utilized.
      Participants were asked to imagine that they were seeing a doctor for a
      respiratory infection. The doctor prescribes antibiotics, but advise postponing
      therapy to see if the disease resolves by itself, for the sake of limiting
      overuse. Respondents were asked to answer how long they could accept postponing
      antibiotic treatment, from 0 to 7 days. The number of days that most people would
      be able to accept postponing treatment was considered the between-subject factor.
      In total, the study sample included 981 respondents with a mean age of 51 years.
      A majority of respondents were men (65.7%). The mean number of days that the
      respondents stated they were willing to postpone antibiotic treatment was
      positively associated with the number of days the respondents were told that most
      people were willing to postpone antibiotic treatment, p < 0.001. There was a
      positive association between number of days they were willing to postpone
      antibiotic treatment and generalized trust, p = 0.001. In conclusion, the results
      showed that the proclaimed public willingness to postpone therapy influenced a
      respondent's willingness to postpone antibiotic therapy in different scenarios.
      Also, generalized trust was positively associated with the willingness to
      postpone therapy. 

PMID- 26318215
TI  - Efficacy of plasma exchange and immunoadsorption in systemic lupus erythematosus
      and antiphospholipid syndrome: A systematic review.
AB  - Extracorporeal treatments have been used since the 1970s in the management of
      systemic lupus erythematosus (SLE). A randomised controlled trial comparing the
      efficacy of standard of care (SOC) combined with plasma exchange against SOC
      alone in patients with lupus nephritis revealed no difference in terms of renal
      outcome. Subsequently, initial expectations have been dampened and further
      experience with plasma exchange is mainly limited to observational studies and
      single case reports. Beneficial effects have been reported in patients with
      refractory disease course or in pregnancy with prior complications due to SLE and
      antiphospholipid syndrome. A more specific form of extracorporeal treatment,
      immunoadsorption (IAS), has emerged as a valuable option in the treatment of SLE.
      In line with the plasma exchange experience, IAS seems to have beneficial effects
      in patients with refractory disease, contraindications to standard
      immunosuppression or during pregnancy. The mechanism IAS relates to autoantibody
      removal but for plasma exchange removal of activated complement components,
      coagulation factors, cytokines and microparticles may also be relevant. Both
      treatment forms have good safety profiles although reactions to blood product
      replacement in plasma exchange and procedure related complications such as
      bleeding or catheter-related infections have occurred. There is a need to more
      clearly define the clinical utility of plasma exchange and IAS in refractory
      lupus and APS subgroups. 

PMID- 26318217
TI  - Catalase-only nanoparticles prepared by shear alone: Characteristics, activity
      and stability evaluation.
AB  - Catalase is a promising therapeutic enzyme; however, it carries risks of
      inactivation and rapid degradation when it is used in practical bioprocess, such
      as delivery in vivo. To overcome the issue, we made catalase-only nanoparticles
      using shear stress alone at a moderate shear rate of 217s(-1) in a coaxial
      cylinder flow cell. Properties of nanoparticles, including particle size,
      polydispersity index and zeta potential, were characterized. The conformational
      changes of pre- and post-sheared catalase were determined using spectroscopy
      techniques. The results indicated that the conformational changes of catalase and
      reduction in alpha-helical content caused by shear alone were less significant
      than that by desolvation method. Catalase-only nanoparticles prepared by single
      shear retained over 90% of its initial activity when compared with the native
      catalase. Catalase nanoparticles lost only 20% of the activity when stored in
      phosphate buffer solution for 72h at 4 degrees C, whereas native catalase lost
      53% under the same condition. Especially, the activity of nanogranulated catalase
      was decreased only slightly in the simulated intestinal fluid containing alpha
      chymotrypsin during 4h incubation at 37 degrees C, implying that the catalase
      nanoparticle was more resistant to the degradation of proteases than native
      catalase molecules. Overall, catalase-only nanoparticles offered a great
      potential to stabilize enzymes for various pharmaceutical applications. 

PMID- 26318216
TI  - Nicotiana sylvestris calcineurin B-like protein NsylCBL10 enhances salt tolerance
      in transgenic Arabidopsis.
AB  - KEY MESSAGE: Nicotiana sylvestris calcineurin B-like protein NsylCBL10 improves
      tolerance to high-salt stress through better maintenance of Na (+) balance. The
      calcineurin B-like (CBL) proteins represent a unique group of plant calcium
      sensors and play an important role in regulating the response of a plant cell to
      the stress. Although many studies have been made in Arabidopsis (Arabidopsis
      thaliana), rice (Oryza sativa) and poplar (Populus trichocarpa), the
      characterization and elucidation of the functions of CBLs in tobacco have not yet
      been reported. In this study, NsylCBL10, a CBL gene showing higher similarities
      to other CBL10 genes, was cloned from Nicotiana sylvestris. NsylCBL10 is
      expressed in most of the tobacco tissues, and the protein targets to the plasma
      membrane specifically. Over-expression of NsylCBL10 enhanced the salt tolerance
      of Arabidopsis wild type plants greatly, and rescued the high-salt-sensitive
      phenotype of Arabidopsis cbl10 mutant. The analysis of ion content indicated that
      over-expressing NsylCBL10 in plants is able to maintain a lower Na(+)/K(+) ratio
      in roots and higher Na(+)/K(+) ratio in shoots, compared with cbl10 mutant. The
      results suggest that NsylCBL10 might play an important role in response to high
      salinity stress in N. sylvestris, by keeping a better ionic homeostasis to reduce
      the damage of toxic ion to the plant cell.

PMID- 26318218
TI  - Neonicotinoid insecticide interact with honeybee odorant-binding protein:
      Implication for olfactory dysfunction.
AB  - The decline of bee population has caused great concern in recent years. A
      noticeable factor points to the neonicotinoid insecticides, which remain in the
      nectar and pollen of plants and impair the olfactory cognition of foraging bees.
      However, it remains elusive that if and how neonicotinoid insecticides interact
      with the olfactory system of bees. Herein, we studied the binding interaction
      between neonicotinoid imidacloprid and ASP2, one odorant-binding protein in
      eastern bees, Apis cerana, by multispectroscopic methods. The results indicate
      that imidacloprid significantly quenched the intrinsic fluorescence of ASP2 as
      the static quenching mode, and expanded the conformation of ASP2 measured by the
      circular dichroism (CD) spectra. The acting force is mainly driven by hydrophobic
      force based on thermodynamic analysis. Docking analysis predicts a formation of a
      hydrogen bond, while the corresponding site-directed mutagenesis indicated that
      the hydrogen bond is not main force here. Moreover, imidacloprid with a sublethal
      dose (0.8ng/bee) clearly decreased the binding affinity of ASP2 to a floral
      volatile, beta-ionone, which had been identified to strongly bind with the wild
      ASP2 before. This study may benefit to evaluate the effect of neonicotinoid
      insecticides on the olfactory cognitive behavior of bees involved in the crops
      pollination. 

PMID- 26318219
TI  - Correction to the paper: "Purification of the YadA membrane anchor for secondary
      structure analysis and crystallization".

PMID- 26318220
TI  - Bifunctional composite from spent "Cyprus coffee" for tetracycline removal and
      phenol degradation: Solar-Fenton process and artificial neural network.
AB  - Removals of tetracycline and photocatalytic degradation of phenol by Fe3O4/coffee
      residue (MCC) were investigated. Brunauer-Emmett-Teller (BET), vibrating sample
      magnetometer (VSM) and Boehm titration were employed to characterize MCC.
      Artificial neural network (ANN) model was developed to predict the tetracycline
      (TC) concentration in the column effluent. Maximum tetracycline adsorption
      capacity of 285.6mg/g was observed in a batch system. High removal efficiency
      (87%) was obtained at 3.3mL/min flow rate, 8.0cm bed height and 50mg/L influent
      TC concentration in a column system. Complete degradation of phenol by solar
      Fenton was attained at 60min irradiation time. Total organic carbon (TOC) removal
      increased to 63.3% in the presence of 1.0g/L MCC, 1.2g/L H2O2 and solar
      irradiation. MCC showed remarkable potential to remove antibiotics from
      wastewater even in the presence of heavy metal (Ni(2+)) via magnetic separation. 

PMID- 26318221
TI  - Analysis of polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins and
      dibenzofurans in particulate and oily films on impervious surfaces.
AB  - During this study wipe sampling was applied to various impervious surfaces for
      the determination of polychlorinated biphenyls (PCBs) and polychlorinated dibenzo
      p-dioxins and dibenzofurans (PCDD/PCDFs) area concentrations. To that end, a wipe
      sampling method based on solvent wetted cotton wipes was evaluated and transfer
      efficiencies of PCBs and PCDD/PCDFs in particulate films (PFs) and oily liquid
      films (OFs) during sampling were investigated. For PFs sufficient transfer
      efficiencies of low concentrated PCB and PCDD/PCDF congeners in 1g/m(2) spiking
      surrogate were achieved after the first wipe using n-hexane as wetting solvent.
      Transfer efficiencies for OFs were the highest in the first wipe if n-hexane or n
      heptane were used rather than toluene. The spiking experiments of OFs showed a
      log-linear correlation between the number of wiping procedures and transfer
      efficiency which indicates that transfer efficiencies were constant in subsequent
      wipes. Furthermore, it was successfully demonstrated that pressurized liquid
      extraction is a suitable tool for the extraction of wipe samples. Finally, the
      feasibility of this wipe sampling method was demonstrated on various impervious
      surfaces of different origin, and concentration levels of PCBs and PCDD/PCDFs in
      wipe samples are discussed. Hereby, remarkably high ?CB6 concentrations of up to
      1400MUg/m(2) (taken at a transformer recycling site) were detected. 

PMID- 26318222
TI  - Evaluating near highway air pollutant levels and estimating emission factors:
      Case study of Tehran, Iran.
AB  - A field sampling campaign was implemented to evaluate the variation in air
      pollutants levels near a highway in Tehran, Iran (Hemmat highway). The field
      measurements were used to estimate road link-based emission factors for average
      vehicle fleet. These factors were compared with results of an in tunnel
      measurement campaign (in Resalat tunnel). Roadside and in-tunnel measurements of
      carbon monoxide (CO) and size-fractionated particulate matter (PM) were conducted
      during the field campaign. The concentration gradient diagrams showed exponential
      decay, which represented a substantial decay, more than 50-80%, in air pollutants
      level in a distance between 100 and 150meters (m) of the highway. The changes in
      particle size distribution by distancing from highway were also captured and
      evaluated. The results showed particle size distribution shifted to larger size
      particles by distancing from highway. The empirical emission factors were
      obtained by using the roadside and in tunnel measurements with a hypothetical box
      model, floating machine model, CALINE4, CT-EMFAC or COPERT. Average CO emission
      factors were estimated to be in a range of 4 to 12g/km, and those of PM10 were
      0.1 to 0.2g/km, depending on traffic conditions. Variations of these emission
      factors under real working condition with speeds were determined. 

PMID- 26318223
TI  - Temporal assessment of copper speciation, bioavailability and toxicity in UK
      freshwaters using chemical equilibrium and biotic ligand models: Implications for
      compliance with copper environmental quality standards.
AB  - Although significant progress has been made in understanding how environmental
      factors modify the speciation, bioavailability and toxicity of metals such as
      copper in aquatic environments, the current methods used to establish water
      quality standards do not necessarily consider the different geological and
      geochemical characteristics of a given site and the factors that affect copper
      fate, bioavailability potential and toxicity. In addition, the temporal variation
      in the concentration and bioavailable metal fraction is also important in
      freshwater systems. The work presented in this paper illustrates the temporal and
      seasonal variability of a range of water quality parameters, and Cu speciation,
      bioavailability and toxicity at four freshwaters sites in the UK. Rivers Coquet,
      Cree, Lower Clyde and Eden (Kent) were selected to cover a broad range of
      different geochemical environments and site characteristics. The monitoring data
      used covered a period of around six years at almost monthly intervals. Chemical
      equilibrium modelling was used to study temporal variations in Cu speciation and
      was combined with acute toxicity modelling to assess Cu bioavailability for two
      aquatic species, Daphnia magna and Daphnia pulex. The estimated copper
      bioavailability, toxicity levels and the corresponding ecosystem risks were
      analysed in relation to key water quality parameters (alkalinity, pH and DOC).
      Although copper concentrations did not vary much during the sampling period or
      between the seasons at the different sites; copper bioavailability varied
      markedly. In addition, through the chronic-Cu BLM-based on the voluntary risk
      assessment approach, the potential environmental risk in terms of the chronic
      toxicity was assessed. A much higher likelihood of toxicity effects was found
      during the cold period at all sites. It is suggested that besides the metal
      (copper) concentration in the surface water environment, the variability and
      seasonality of other important water quality parameters should be considered in
      setting appropriately protective environmental quality standards for metals. 

PMID- 26318224
TI  - Determination of pharmaceutical residues in drinking water in Poland using a new
      SPE-GC-MS(SIM) method based on Speedisk extraction disks and DIMETRIS
      derivatization.
AB  - The presence of pharmaceuticals in drinking water, even at very low
      concentrations, has raised concerns among stakeholders such as drinking-water
      regulators, governments, water suppliers and the public, with regard to the
      potential risks to humans. Despite this, the occurrence and the fate of
      pharmaceuticals in drinking waters of many countries (e.g. in Poland) remains
      unknown. There is a lack of sufficiently sensitive and reliable analytical
      methods for such analyses and a need for more in-depth hydrogeological analysis
      of the possible sources of drug residues in drinking water. In this paper, a
      multi-residual method for the simultaneous determination of seventeen human
      pharmaceuticals in drinking waters has been developed. Large-volume extractions
      using Speedisk extraction disks, and derivatization prior to GC-MS-SIM analysis
      using a new silylating agent DIMETRIS were applied. The method detection limits
      (MDLs) ranged from 0.9 to 5.7ng/L and the absolute recoveries of the target
      compounds were above 80% for most analytes. The developed method was successfully
      applied in the analysis of the target compounds in drinking water collected in
      Gdansk (Poland), and of the 17 pharmaceuticals, 6 compounds were detected at
      least once. During the investigation, the geomorphology of the site region was
      taken into account, possible sources of pharmaceuticals in the analysed drinking
      water samples were investigated, and the presence of the drugs in ground and
      surface waters, raw and treated drinking waters was determined. Concentrations
      were also compared with those observed in other countries. As a result, this
      study has not only developed a new analytical method for determining
      pharmaceuticals in drinking waters as well as rendering missing information for
      Poland (a country with one of the highest consumptions of pharmaceuticals in
      Europe), but it also presents a modelled in-depth hydrogeological analysis of the
      real sources of drugs in drinking waters. 

PMID- 26318225
TI  - Atmospheric impacts of black carbon emission reductions through the strategic use
      of biodiesel in California.
AB  - The use of biodiesel as a replacement for petroleum-based diesel fuel has gained
      interest as a strategy for greenhouse gas emission reductions, energy security,
      and economic advantage. Biodiesel adoption may also reduce particulate elemental
      carbon (EC) emissions from conventional diesel engines that are not equipped with
      after-treatment devices. This study examines the impact of biodiesel blends on EC
      emissions from a commercial off-road diesel engine and simulates the potential
      public health benefits and climate benefits. EC emissions from the commercial off
      road engine decreased by 76% when ultra-low sulfur commercial diesel (ULSD) fuel
      was replaced by biodiesel. Model calculations predict that reduced EC emissions
      translate directly into reduced EC concentrations in the atmosphere, but the
      concentration of secondary particulate matter was not directly affected by this
      fuel change. Redistribution of secondary particulate matter components to
      particles emitted from other sources did change the size distribution and
      therefore deposition rates of those components. Modification of meteorological
      variables such as water content and temperature influenced secondary particulate
      matter formation. Simulations with a source-oriented WRF/Chem model (SOWC) for a
      severe air pollution episode in California that adopted 75% biodiesel blended
      with ULSD in all non-road diesel engines reduced surface EC concentrations by up
      to 50% but changed nitrate and total PM2.5 mass concentrations by less than +/
      5%. These changes in concentrations will have public health benefits but did not
      significantly affect radiative forcing at the top of the atmosphere. The removal
      of EC due to the adoption of biodiesel produced larger coatings of secondary
      particulate matter on other atmospheric particles containing residual EC leading
      to enhanced absorption associated with those particles. The net effect was a
      minor change in atmospheric optical properties despite a large change in
      atmospheric EC concentrations. These results emphasize the importance of
      considering EC mixing state in climate research. 

PMID- 26318226
TI  - Accumulation of steroid hormones in soil and its adjacent aquatic environment
      from a typical intensive vegetable cultivation of North China.
AB  - Steroid hormones released from manure agricultural application are a matter of
      global concern. The residual levels of steroid hormones were studied in a typical
      intensive vegetable cultivation area in northeast China, with a long history of
      heavy manure application. Seven steroids (estrone, 17alpha-estradiol, 17beta
      estradiol, estriol, testosterone, androstendione and progesterone) were analyzed
      from soil sampled from vegetable greenhouses, from sediments and water from the
      adjacent drainage ditch and from the groundwater. The results showed that target
      steroids were detected in the soil samples, with detection frequencies varying
      from 3.13 to 100%. The steroid concentrations varied substantially in soils,
      ranging from below the detection limit to 109.7MUg.kg(-1). Three steroids
      progesterone, androstendione and estrone-were found to have relatively high
      residue concentrations in soil, with maximum concentrations of 109.7, 9.83 and
      13.30MUg.kg(-1), respectively. In adjacent groundwater, all the steroids, with
      the exception of estrone, were detected in one or more of the 13 groundwater
      samples. The concentrations of steroids in groundwater ranged from below the
      method detection limit to 2.38ng.L(-1). Six of the seven (excluding
      androstendione) were detected in drainage ditch water samples, with
      concentrations ranging from below the detection limit to 14ng.L(-1).
      Progesterone, androstendione and estrone accumulated relatively easily in soils;
      their concentrations in groundwater were lower than those of other steroids. The
      concentrations of testosterone and estriol were relatively low in soil, while in
      groundwater were higher than those of other steroids. The residual levels of
      steroids in soil and groundwater showed a clear spatial variation in the study
      area. The residual levels of steroid hormones in soil varied substantially
      between differently planted greenhouses. 

PMID- 26318227
TI  - Trends in pesticide concentrations and use for major rivers of the United States.
AB  - Trends in pesticide concentrations in 38 major rivers of the United States were
      evaluated in relation to use trends for 11 commonly occurring pesticide
      compounds. Pesticides monitored in water were analyzed for trends in
      concentration in three overlapping periods, 1992-2001, 1997-2006, and 2001-2010
      to facilitate comparisons among sites with variable sample distributions over
      time and among pesticides with changes in use during different periods and
      durations. Concentration trends were analyzed using the SEAWAVE-Q model, which
      incorporates intra-annual variability in concentration and measures of long-term,
      mid-term, and short-term streamflow variability. Trends in agricultural use
      within each of the river basins were determined using interval-censored
      regression with high and low estimates of use. Pesticides strongly dominated by
      agricultural use (cyanazine, alachlor, atrazine and its degradate
      deethylatrazine, metolachlor, and carbofuran) had widespread agreement between
      concentration trends and use trends. Pesticides with substantial use in both
      agricultural and nonagricultural applications (simazine, chlorpyrifos, malathion,
      diazinon, and carbaryl) had concentration trends that were mostly explained by a
      combination of agricultural-use trends, regulatory changes, and urban use changes
      inferred from concentration trends in urban streams. When there were differences,
      concentration trends usually were greater than use trends (increased more or
      decreased less). These differences may occur because of such factors as
      unaccounted pesticide uses, delayed transport to the river through groundwater,
      greater uncertainty in the use data, or unquantified land use and management
      practice changes. 

PMID- 26318228
TI  - Effect of breeding stage and photoperiod on gonadal and serotonergic axes in
      domestic ganders.
AB  - Reduction in reproductive potential of ganders with progress in seasonal breeding
      is a known problem in commercial geese production. The role of changes in
      hypothalamic-pituitary-gondal axis and testis functions in this process is not
      clear. This article presents studies on the hypothalamic (GnRH-I, vasoactive
      intestinal peptide), pituitary (LHbeta, prolactin [PRL], PRL receptor [PRLR]),
      testis (PRLR) axis messenger RNA (mRNA) expression during different stages of the
      breeding period and photoperiodic conditions. Testis mass; histologic and
      functional (testosterone [T]) parameters; and plasma concentrations of T, LH, and
      PRL were evaluated. We collected (six times) samples from 2-year-old ganders (n =
      48) maintained in short day (10L:14D) during the period from November to July.
      Moreover, in the peak of sexual activity (March), an additional group was on
      exposure (6 weeks) to long day (LD; 16L:8D). During the first half of
      reproduction (January, March; photosensitive period), GnRH-I (1.9 vs. 0.3
      relative quantity [RQ]) and LHbeta (3.0 vs. 0.7 RQ) mRNA transcript expression
      and concentrations of T (1.9-2.9 vs. 0.3 ng/mL), LH (13.6-7.4 vs. 0.7 ng/mL) were
      found to be higher (P < 0.05) than at the end of breeding (July). With progress
      in breeding, marked elevation (P < 0.05) in PRL (22.0-387.1 ng/mL) concentration
      related to similar changes in vasoactive intestinal peptide (0.9-3.0 RQ) and PRL
      mRNA abundance (1.3-11.5 RQ; May, July) was observed. However, testis PRLR mRNA
      increased (P < 0.05) only at the end of reproduction (1.2 RQ) compared to the
      peak of sexual activity (0.4 RQ; March). Furthermore, changes in mRNA transcript
      expression of the lactotrophic axis were accompanied with reduction of testis
      weight (left: 11.1-5.8 g), spermatogenesis (spermatogenic index: 5.4-3.0), and
      steroidogenesis (T: 24.8-1.3 ng/g testis), which may suggest their pivotal
      inhibitory modulation role in the regression of seasonal reproductive activity in
      ganders. The LD conditions (similar to spring-summer) resulted in earlier
      peripheral changes in T (0.9 vs. 1.8 ng/mL), LH (1.1 vs. 3.8 ng/mL), and PRL
      (296.1 vs. 161.2 ng/mL) concentrations than in short day, and this may be related
      to the advance in the timing of the sexual activity failure observed under
      natural light regimes. The lack of differences in gonadal and lactotrophic axis
      mRNA expression after LD treatment suggested a regulation based on the
      posttranslational mechanisms or modification of transcript or protein.

PMID- 26318229
TI  - Sperm head phenotype and male fertility in ram semen.
AB  - Although there is ample evidence for the effects of sperm head shape on sperm
      function, its impact on fertility has not been explored in detail at the
      intraspecific level in mammals. Here, we assess the relationship between sperm
      head shape and male fertility in a large-scale study in Manchega sheep (Ovis
      aries), which have not undergone any selection for fertility. Semen was collected
      from 83 mature rams, and before insemination, head shapes were measured for five
      parameters: area, perimeter, length, width, and p2a (perimeter(2)/2*pi*area)
      using a computer-assisted sperm morphometric analysis. In addition, a cluster
      analysis using sperm head length and p2a factor was performed to determine sperm
      subpopulations (SPs) structure. Our results show the existence of four sperm SPs,
      which present different sperm head phenotype: SP1 (large and round), SP2 (short
      and elongated), SP3 (shortest and round), and SP4 (large and the most elongated).
      No relationships were found between males' fertility rates and average values of
      sperm head dimensions. However, differences in fertility rates between rams were
      strongly associated to the proportion of spermatozoa in an ejaculate SP with
      short and elongated heads (P < 0.001). These findings show how the heterogeneity
      in sperm head shape of the ejaculate has an effect on reproductive success, and
      highlight the important role of modulation of the ejaculate at the intraspecific
      level. 

PMID- 26318230
TI  - Plasma insulin-like peptide 3 concentrations are acutely regulated by luteinizing
      hormone in pubertal Japanese Black beef bulls.
AB  - Insulin-like peptide 3 (INSL3) is a major secretory product of testicular Leydig
      cells. The mechanism of acute regulation of INSL3 secretion is still unknown. The
      present study was undertaken in pubertal beef bulls to (1) determine the temporal
      relationship of pulsatile secretion among LH, INSL3, and testosterone and (2)
      monitor acute regulation of INSL3 secretion by LH using GnRH analogue and hCG.
      Blood samples were collected from Japanese Black beef bulls (N = 6) at 15-minute
      intervals for 8 hours. Moreover, blood samples were collected at -0.5, 0, 1, 2,
      3, 4, 5, and 6 hours after GnRH treatment and -0.5, 0, 2, 4, and 8 hours on the
      day of treatment (Day 0), and Days 1, 2, 4, 8, and 12 after hCG treatment.
      Concentrations of LH, INSL3, and testosterone determined by EIAs indicated that
      secretion in the general circulation was pulsatile. The frequency of LH, INSL3,
      and testosterone pulses was 4.7 +/- 0.9, 3.8 +/- 0.2, and 1.0 +/- 0.0,
      respectively, during the 8-hour period. Seventy percent of these INSL3 pulses
      peaked within 1 hour after a peak of an LH pulse had occurred. The mean increase
      (peak per basal concentration) of testosterone pulses was higher (P < 0.001) than
      that of INSL3 pulses. After GnRH treatment, LH concentrations increased (P <
      0.01) dramatically 1 hour after treatment and remained high (P < 0.05) until the
      end of sampling, whereas an elevated (P < 0.05) INSL3 concentration occurred at
      1, 2, 5, and 6 hours after treatment. Testosterone concentrations increased (P <
      0.01) 1 hour after the treatment and remained high until the end of sampling.
      After hCG treatment, an increase of INSL3 concentration occurred at 2 and 4
      hours, and Days 2, 4, and 8 after treatment (P < 0.05), whereas in case of
      testosterone, concentrations remained high (P < 0.01) until Day 8 after
      treatment. The increase (maximum per pretreatment concentration) of INSL3
      concentrations after injecting GnRH or hCG was much lower (P < 0.001) than that
      of testosterone. In conclusion, secretion of INSL3 in blood of bulls occurred in
      a pulsatile manner. We inferred an acute regulation of INSL3 by LH in bulls
      because INSL3 concentrations increased immediately after endogenous and exogenous
      LH stimulation. The increase of INSL3 concentrations by LH was much lower than
      that of testosterone in bulls. 

PMID- 26318231
TI  - Effect of increased testicular temperature on seminal plasma proteome of the ram.
AB  - The present study evaluated the effects of heat stress on the ram seminal plasma
      proteome. Six Morada Nova rams were scrotal insulated for 8 days. Scrotal
      circumference, sperm parameters, and seminal fluid proteins were evaluated before
      (Day 0) and twice during scrotal insulation (Days 4 and 8), and weekly until
      semen parameters returned to preinsulation values (normal). Seminal proteins were
      analyzed by two-dimensional SDS-PAGE and mass spectrometry. Scrotal circumference
      decreased from 30 +/- 0.4 cm on Day 0 to 22.6 +/- 0.6 cm on Day 36 (P < 0.05) and
      became equivalent to preinsulation values on Day 71. Motile sperm became nearly
      absent from Day 8 to Day 64 but returned to normal on Day 113. Percentage of
      normal sperm changed similarly and returned to normal on Day 106. Rams were
      azoospermic between Days 29 and 64, and sperm concentration came back to normal
      on Day 92. The number of spots/two-dimensional gel reduced from 256 +/- 31 on Day
      0 to 104 +/- 14 on Day 29 (when rams were azoospermic) and then increased to 183
      +/- 9 on Day 113 (P < 0.05), similar to spot counts before insulation. The
      intensities of 24 spots, referring to 17 seminal plasma proteins, were affected
      by treatment (P < 0.05). After insulation, seminal plasma had greater expression
      of actin (two isoforms), albumin, heat shock protein 70 kDa, protein DJ-1,
      HRPE773-like, C-reactive protein precursor, bodhesin-2 (one isoform),
      spermadhesins. Most protein spots had the greatest intensity between Days 8 and
      29, returning to preinsulation values on Day 113 (when many sperm criteria
      returned to normal). Proteins downregulated after scrotal insulation included
      dipeptidyl peptidase 3, isoforms of heat shock protein 90 kDa, RSVP22, MMP2 and
      of Bdh2. In this case, RSVP22 was reduced on Day 113 and all others, on Day 134.
      Expression of MMP2 and HSP90.1 was reduced throughout the study. Integrin beta5,
      V-type H(+)-ATPase subunit A, ZBTB 42-like protein, isoforms of Bdh2, PSP-I, and
      RSVP22 were upregulated after testis insulation. Intensities of these spots were
      maximum (P < 0.05) 8 days after insulation started or on Day 29. Expression of
      most of such proteins returned to normal on Day 113. In conclusion, scrotal
      insulation affected testis and sperm parameters of rams, indicating alterations
      in both spermatogenesis and sperm maturation. Changes of seminal plasma proteome
      were coincidental with variations in semen parameters. Proteins affected by heat
      challenge are potentially involved in sperm protection, maturation, and
      fertilization. 

PMID- 26318232
TI  - Development of computer-assisted sperm analysis plugin for analyzing sperm motion
      in microfluidic environments using Image-J.
AB  - We modified a previously reported computer-assisted sperm analysis (CASA) plugin
      for Image-J to enable analyzing motion of sperm cells in microfluidic
      environments. Microfluidics is increasingly being used in sperm-related
      applications such as sperm selection, IVF, and sperm motion behavior. Current
      CASA systems are not capable of analyzing motion of sperm cells in microfluidic
      devices where both sperm cells and the liquid itself are constantly moving,
      contrary to the conventional situation of sperm cells moving in a stationary
      liquid. We resolved this deficiency in the modified plugin reported here and
      built an image processing pipeline to enhance object detection, which increased
      CASA accuracy considerably. More importantly, particle tracking was improved and
      modified to accommodate sperm cells going out of focus for short periods during
      swimming on the same track. This last feature is particularly important in
      microfluidics where height of the microchannel is larger than that of CASA custom
      chambers to avoid channel blockage; this increased height causes sperm cells to
      frequently come in and out of focus. New parameters were introduced to allow
      studying new aspects of sperm motion behavior such as rheotaxis and wall
      tracking. The new plugin was able to detect and analyze motion of human, bull,
      and chicken sperm. A preliminary study using this tool agreed well with
      previously reported studies on rheotaxis and wall tracking behavior of sperm. 

PMID- 26318233
TI  - The conformation effect of the diamine bridge on the stability of dinuclear
      platinum(II) complexes and their hydrolysis.
AB  - In this paper, the hydrolysis process of a bisplatinum complex containing the
      flexible chain 1,6-hexanediamine between the two metal centers was investigated
      through the use of density functional theory (DFT) with the analysis of the role
      of the spacing group arrangement on the values of free energy activation barrier.
      All structures were fully optimized in aqueous solution using implicit model for
      solvent at DFT level. The energy profiles for the hydrolysis reaction were
      determined by using the supermolecule approach. Five transition states were
      proposed differing by the conformation of the bridge group, and the activation
      free energy calculated as a weighted average within the selected forms. The Gibbs
      population for reactant was used as a statistical weight leading to the predicted
      value of 23.1kcalmol(-1), in good accordance with experiment, 23.8kcalmol(-1).
      Our results suggests that for 1,6-hexanediamine bridge ligand, the extend forms
      with average torsional angle over the carbon chain larger than 130 degrees  have
      the greatest contribution to the hydrolysis kinetics. The results presented here
      point out that the hydrolysis mechanism might follow different paths for each
      conformation and each of these contributes to the observed energy barrier. 

PMID- 26318234
TI  - Feasibility and safety of in-bed cycling for physical rehabilitation in the
      intensive care unit.
AB  - PURPOSE: The purpose was to evaluate the feasibility and safety of in-bed cycle
      ergometry as part of routine intensive care unit (ICU) physical therapist (PT)
      practice. MATERIALS AND METHODS: Between July 1, 2010, and December 31, 2011, we
      prospectively identified all patients admitted to a 16-bed medical ICU receiving
      cycling by a PT, prospectively collected data on 12 different potential safety
      events, and retrospectively conducted a chart review to obtain specific details
      of each cycling session. RESULTS: Six hundred eighty-eight patients received PT
      interventions, and 181 (26%) received a total of 541 cycling sessions (median
      [interquartile range {IQR}] cycling sessions per patient, 2 [1-4]). Patients'
      mean (SD) age was 57 (17) years, and 103 (57%) were male. The median (IQR) time
      from medical ICU admission to first PT intervention and first cycling session was
      2 (1-4) and 4 (2-6) days, respectively, with a median (IQR) cycling session
      duration of 25 (18-30) minutes. On cycling days, the proportion of patients
      receiving mechanical ventilation, vasopressor infusions, and continuous renal
      replacement therapy was 80%, 8%, and 7%, respectively. A single safety event
      occurred, yielding a 0.2% event rate (95% upper confidence limit, 1.0%).
      CONCLUSIONS: Use of in-bed cycling as part of routine PT interventions in ICU
      patients is feasible and appears safe. Further study of the potential benefits of
      early in-bed cycling is needed.

PMID- 26318235
TI  - Development, upscaling and validation of the purification process for human-cl
      rhFVIII (Nuwiq(r)), a new generation recombinant factor VIII produced in a human
      cell-line.
AB  - INTRODUCTION: Human-cl rhFVIII (Nuwiq(r)), a new generation recombinant factor
      VIII (rFVIII), is the first rFVIII produced in a human cell-line approved by the
      European Medicines Agency. AIMS: To describe the development, upscaling and
      process validation for industrial-scale human-cl rhFVIII purification. METHODS
      AND RESULTS: The purification process involves one centrifugation, two
      filtration, five chromatography columns and two dedicated pathogen clearance
      steps (solvent/detergent treatment and 20 nm nanofiltration). The key
      purification step uses an affinity resin (VIIISelect) with high specificity for
      FVIII, removing essentially all host-cell proteins with >80% product recovery.
      The production-scale multi-step purification process efficiently removes process-
      and product-related impurities and results in a high-purity rhFVIII product, with
      an overall yield of ~50%. Specific activity of the final product was >9000 IU/mg,
      and the ratio between active FVIII and total FVIII protein present was >0.9. The
      entire production process is free of animal-derived products. Leaching of
      potential harmful compounds from chromatography resins and all pathogens tested
      were below the limit of quantification in the final product. CONCLUSIONS: Human
      cl rhFVIII can be produced at 500 L bioreactor scale, maintaining high purity and
      recoveries. The innovative purification process ensures a high-purity and high
      quality human-cl rhFVIII product with a high pathogen safety margin.

PMID- 26318236
TI  - Identification and functional evaluation of Leishmania braziliensis Nicotinamide
      Mononucleotide Adenylyltransferase.
AB  - The progressive increase in Leishmania resistance to current control approaches
      prompts the need to develop therapeutic strategies based on comprehensive
      knowledge of the parasite's biology. The enzyme Nicotinamide Mononucleotide
      Adenylyltransferase (NMNAT, EC 2.7.7.1) catalyzes the central step in
      nicotinamide adenine dinucleotide (NAD(+)) biosynthesis, making it essential for
      the survival of all organisms. NAD(+) metabolism is related to the maintenance of
      several biochemical, cellular, and physiological processes; consequently, the
      characterization and analysis of the enzymes involved in its biosynthesis
      represent key steps in the development of control strategies. In this study, the
      NMNAT enzymes of different Leishmania species were identified using
      bioinformatics procedures. The sequences were used to construct structural
      homology models that revealed characteristic elements common to NMNATs. The open
      reading frame of Leishmania braziliensis NMNAT was cloned from complementary DNA
      and the enzymatic activity of the corresponding recombinant protein was confirmed
      through enzymatic assays. Primary structure analysis revealed a Leishmania
      specific amino-terminal insertion in NMNAT. The deletion of this insertion is
      negatively correlated with in vitro enzymatic activity. From our observations, we
      suggest the amino-terminal insertion of Leishmania NMNATs as a promising
      pharmacological target for the development of specific control strategies. 

PMID- 26318237
TI  - Chitinase III in Euphorbia characias latex: Purification and characterization.
AB  - This paper deals with the purification of a class III endochitinase from
      Euphorbia characias latex. Described purification method includes an effective
      novel separation step using magnetic chitin particles. Application of magnetic
      affinity adsorbent noticeably simplifies and shortens the purification procedure.
      This step and the subsequently DEAE-cellulose chromatography enable to obtain the
      chitinase in homogeneous form. One protein band is present on PAGE in non
      denaturing conditions and SDS-PAGE profile reveals a unique protein band of 36.5
      +/- 2 kDa. The optimal chitinase activity is observed at 50  degrees C, pH 5.0.
      E. characias latex chitinase is able to hydrolyze colloidal chitin giving, as
      reaction products, N-acetyl-D-glucosamine, chitobiose and chitotriose. Moreover,
      we observed that calcium and magnesium ions enhance chitinase activity. Finally,
      we cloned the cDNA encoding the E. characias latex chitinase. The partial cDNA
      nucleotide sequence contains 762 bp, and the deduced amino acid sequence (254
      amino acids) is homologous to the sequence of several plant class III
      endochitinases.

PMID- 26318238
TI  - Development of a rapid high-efficiency scalable process for acetylated Sus scrofa
      cationic trypsin production from Escherichia coli inclusion bodies.
AB  - Trypsin is one of the most important enzymatic tools in proteomics and
      biopharmaceutical studies. Here, we describe the complete recombinant expression
      and purification from a trypsinogen expression vector construct. The Sus scrofa
      cationic trypsin gene with a propeptide sequence was optimized according to
      Escherichia coli codon-usage bias and chemically synthesized. The gene was
      inserted into pET-11c plasmid to yield an expression vector. Using high-density
      E. coli fed-batch fermentation, trypsinogen was expressed in inclusion bodies at
      1.47 g/L. The inclusion body was refolded with a high yield of 36%. The purified
      trypsinogen was then activated to produce trypsin. To address stability problems,
      the trypsin thus produced was acetylated. The final product was generated upon
      gel filtration. The final yield of acetylated trypsin was 182 mg/L from a 5-L
      fermenter. Our acetylated trypsin product demonstrated higher BAEE activity
      (30,100 BAEE unit/mg) than a commercial product (9500 BAEE unit/mg, Promega). It
      also demonstrated resistance to autolysis. This is the first report of production
      of acetylated recombinant trypsin that is stable and suitable for scale-up.

PMID- 26318239
TI  - An objective electrophysiological marker of face individualisation impairment in
      acquired prosopagnosia with fast periodic visual stimulation.
AB  - One of the most striking pieces of evidence for a specialised face processing
      system in humans is acquired prosopagnosia, i.e. the inability to individualise
      faces following brain damage. However, a sensitive and objective non-behavioural
      marker for this deficit is difficult to provide with standard event-related
      potentials (ERPs), such as the well-known face-related N170 component reported
      and investigated in-depth by our late distinguished colleague Shlomo Bentin. Here
      we demonstrate that fast periodic visual stimulation (FPVS) in electrophysiology
      can quantify face individualisation impairment in acquired prosopagnosia. In
      Experiment 1 (Liu-Shuang et al., 2014), identical faces were presented at a rate
      of 5.88 Hz (i.e., ~ 6 images/s, SOA=170 ms, 1 fixation per image), with different
      faces appearing every 5th face (5.88 Hz/5=1.18 Hz). Responses of interest were
      identified at these predetermined frequencies (i.e., objectively) in the EEG
      frequency-domain data. A well-studied case of acquired prosopagnosia (PS) and a
      group of age- and gender-matched controls completed only 4 * 1-min stimulation
      sequences, with an orthogonal fixation cross task. Contrarily to controls, PS did
      not show face individualisation responses at 1.18 Hz, in line with her
      prosopagnosia. However, her response at 5.88 Hz, reflecting general visual
      processing, was within the normal range. In Experiment 2 (Rossion et al., 2015),
      we presented natural (i.e., unsegmented) images of objects at 5.88 Hz, with face
      images shown every 5th image (1.18 Hz). In accordance with her preserved ability
      to categorise a face as a face, and despite extensive brain lesions potentially
      affecting the overall EEG signal-to-noise ratio, PS showed 1.18 Hz face-selective
      responses within the normal range. Collectively, these findings show that fast
      periodic visual stimulation provides objective and sensitive electrophysiological
      markers of preserved and impaired face processing abilities in the
      neuropsychological population.

PMID- 26318240
TI  - Thematic role assignment in the posterior parietal cortex: A TMS study.
AB  - Verbs denote relations between entities acting a role in an event. Thematic roles
      are essential to the correct use of verbs and involve both semantic and syntactic
      aspects. We used repetitive Transcranial Magnetic Stimulation (rTMS) to study the
      involvement of three different left parietal sites in the understanding of
      thematic roles. In a sentence-to-picture matching task, twelve participants were
      asked to judge whether or not a given picture matched with a written sentence.
      Pictures represented simple reversible actions, and sentences were in the active
      or passive diathesis. Whereas both active and passive sentences require the
      correct encoding of thematic roles, passives also imply thematic reanalysis, as
      the canonical order of thematic roles is systematically reversed. The experiment
      was divided in three sessions. In each session a different parietal site
      (anterior, middle, posterior) was stimulated at 5 Hz in an event-related fashion,
      time-locked to the presentation of visual stimuli. Results showed increased
      accuracy for passive sentences following posterior parietal stimulation. The
      effect appeared to be (a) TMS-related, as no effect was observed in a control, no
      TMS experiment with eighteen new participants; (b) independent from semantic
      processes involved in word-picture association, as no TMS-related effects were
      observed in a picture-word matching task. We interpret the results as showing
      that the posterior parietal site is specifically involved in the assignment of
      thematic roles, in particular when the correct interpretation of a sentence
      requires reanalysis of temporarily encoded thematic roles, as in passive
      reversible sentences.

PMID- 26318241
TI  - Intracranial arterial stenosis in Ecuadorian Natives/Mestizos. A population-based
      study in older adults (The Atahualpa Project).
AB  - BACKGROUND: Intracranial arterial stenosis (IAS) is more prevalent among Asians,
      Blacks and Caribbean Hispanics than in Whites. However, there is no information
      on the importance of this common cause of stroke among Mestizo/Native populations
      of Latin America. We aimed to assess prevalence and correlates of IAS in an
      indigenous Ecuadorian population of older adults. METHODS: Atahualpa residents
      aged >=60 years were identified during door-to-door surveys and invited to
      undergo brain magnetic resonance imaging (MRI) and magnetic resonance angiography
      (MRA) of intracranial vessels for identification of stroke lesions and arterial
      stenosis. Prevalence of IAS was assessed in patients with strokes as well as in
      stroke-free individuals. A logistic regression model was constructed with stroke
      as the outcome, IAS as the exposure, and confounders (demographics and
      cardiovascular risk factors) as independent variables. RESULTS: Out of 267
      participants (mean age 71 +/- 8 years, 57% women), 15 (5.6%) had intracranial
      arterial stenosis, including 10 out of 52 (19.2%) persons with stroke and five
      out of 215 (2.3%) without. The multivariate logistic regression model showed
      significant association of IAS with stroke after adjusting for demographics and
      cardiovascular risk factors (OR: 7.9, 95% C.I.: 2.2-27.8, p=0.001). Mechanisms
      underlying stroke in patients with IAS included perforator occlusion, artery-to
      artery embolism and hypoperfusion. CONCLUSIONS: Prevalence of IAS in Ecuadorian
      Natives/Mestizos is similar to that in Asians. Individuals aged >=60 years with
      IAS are almost eight times more likely to have a stroke after adjusting for
      confounding variables.

PMID- 26318242
TI  - Effects of dissolved oxygen and pH on nitrous oxide production rates in
      autotrophic partial nitrification granules.
AB  - The effects of dissolved oxygen (DO) and pH on nitrous oxide (N2O) production
      rates and pathways in autotrophic partial nitrification (PN) granules were
      investigated at the granular level. N2O was primarily produced by
      betaproteobacterial ammonia-oxidizing bacteria, mainly Nitrosomonas europaea, in
      the oxic surface layer (<200MUm) of the autotrophic PN granules. N2O production
      increased with increasing bulk DO concentration owing to activation of the
      ammonia (i.e., hydroxylamine) oxidation in this layer. The highest N2O emissions
      were observed at pH 7.5, although the ammonia oxidation rate was unchanged
      between pH 6.5 and 8.5. Overall, the results of this study suggest that in situ
      analyses of PN granules are essential to gaining insight into N2O emission
      mechanisms in a granule. 

PMID- 26318243
TI  - (13)C-metabolic flux analysis of lipid accumulation in the oleaginous fungus
      Mucor circinelloides.
AB  - The oleaginous fungus Mucor circinelloides is of industrial interest because it
      can produce high levels of polyunsaturated fatty acid gamma-linolenic acid. M.
      circinelloides CBS 277.49 is able to accumulate less than 15% of cell dry weight
      as lipids, while M. circinelloides WJ11 can accumulate lipid up to 36%. In order
      to better understand the mechanisms behind the differential lipid accumulation in
      these two strains, tracer experiments with (13)C-glucose were performed with the
      growth of M. circinelloides and subsequent gas chromatography-mass spectrometric
      detection of (13)C-patterns in proteinogenic amino acids was carried out to
      identify the metabolic network topology and estimate intracellular fluxes. Our
      results showed that the high oleaginous strain WJ11 had higher flux of pentose
      phosphate pathway and malic enzyme, lower flux in tricarboxylic acid cycle,
      higher flux in glyoxylate cycle and ATP: citrate lyase, together, it might
      provide more NADPH and substrate acetyl-CoA for fatty acid synthesis. 

PMID- 26318244
TI  - Transesterification of activated sludge in subcritical solvent mixture.
AB  - Most previous studies reported in literature on biodiesel production from sludge
      were performed by acid catalyzed transesterification that required long reaction
      time (about 24h) and high methanol loading. The objective of this study was to
      investigate the in situ transesterification of sludge in subcritical mixture of
      methanol and acetic acid. At 250 degrees C and a solvent (85% methanol and 15%
      acetic acid) to sludge ratio of 5 (mLg(-1)), a FAME yield of 30.11% can be
      achieved in 30min, compared to the yield of 35% obtained by the acid-catalyzed
      (4% H2SO4) transesterification which required 24h at 55 degrees C and a methanol
      to sludge ratio of 25 (mLg(-1)). The method developed in this study avoided using
      mineral acid, significantly reduced reaction time and methanol loading to achieve
      comparable FAME yield. 

PMID- 26318245
TI  - Hydrolysis of cellulose catalyzed by quaternary ammonium perrhenates in 1-allyl-3
      methylimidazolium chloride.
AB  - Quaternary ammonium perrhenates were applied as catalyst to promote the
      hydrolysis of cellulose in 1-allyl-3-methylimidazolium chloride ([Amim]Cl). The
      quaternary ammonium perrhenates displayed good catalytic performance for
      cellulose hydrolysis. Water was also proven to be effective to promote cellulose
      hydrolysis. Accordingly, 97% of total reduced sugar (TRS) and 42% of glucose
      yields could be obtained under the condition of using 5mol% of tetramethyl
      ammonium perrhenate as catalyst, 70MUL of water, ca. 0.6mmol of microcrystalline
      cellulose (MCC) and 2.0g of [Amim]Cl as solvent under microwave irradiation for
      30min at 150 degrees C (optimal conditions). The influence of quaternary ammonium
      cation on the efficiency of cellulose hydrolysis was examined based on different
      cation structures of perrhenates. The mechanism on perrhenate catalyzed cellulose
      hydrolysis is also discussed, whereas hydrogen bonding between ReO4 anion and
      hydroxyl groups of cellulose is assumed to be the key step for depolymerization
      of cellulose. 

PMID- 26318246
TI  - Cutaneous vaccination - Protective immunization is just a skin-deep step away.

PMID- 26318247
TI  - Diverse antigenic site targeting of influenza hemagglutinin in the murine
      antibody recall response to A(H1N1)pdm09 virus.
AB  - Here we define the epitopes on HA that are targeted by a group of 9 recombinant
      monoclonal antibodies (rmAbs) isolated from memory B cells of mice, immunized by
      infection with A(H1N1)pdm09 virus followed by a seasonal TIV boost. These rmAbs
      were all reactive against the HA1 region of HA, but display 7 distinct binding
      footprints, targeting each of the 4 known antigenic sites. Although the rmAbs
      were not broadly cross-reactive, a group showed subtype-specific cross-reactivity
      with the HA of A/South Carolina/1/18. Screening these rmAbs with a panel of human
      A(H1N1)pdm09 virus isolates indicated that naturally-occurring changes in HA
      could reduce rmAb binding, HI activity, and/or virus neutralization activity by
      rmAb, without showing changes in recognition by polyclonal antiserum. In some
      instances, virus neutralization was lost while both ELISA binding and HI activity
      were retained, demonstrating a discordance between the two serological assays
      traditionally used to detect antigenic drift. 

PMID- 26318248
TI  - Subpopulations of M-MDSCs from mice infected by an immunodeficiency-causing
      retrovirus and their differential suppression of T- vs B-cell responses.
AB  - Monocytic (CD11b(+)Ly6G(+/-/Lo)Ly6C(+)) myeloid derived suppressor cells (M
      MDSCs) expand following murine retroviral LP-BM5 infection and suppress ex vivo
      polyclonal T-cell and B-cell responses. M-MDSCs 3 weeks post LP-BM5 infection
      have decreased suppression of T-cell, but not B-cell, responses and alterations
      in the degree of iNOS/NO dependence of suppression. M-MDSCs from LP-BM5 infected
      mice were sorted into four quadrant populations (Ly6C/CD11b density): all
      quadrants suppressed B-cell responses, but only M-MDSCs expressing the highest
      levels of Ly6C and CD11b (Q2) significantly suppressed T-cell responses. Further
      subdivision of this Q2 population revealed the Ly6C(+/Hi) M-MDSC subpopulation as
      the most suppressive, inhibiting T- and B-cell responses in a full, or partially,
      iNOS/NO-dependent manner, respectively. In contrast, the lower/moderate levels of
      suppression by the Ly6C(+/Lo) and Ly6C(+/Mid) M-MDSC Q2 subpopulations, whether
      versus T- and/or B-cells, displayed little/no iNOS dependency for suppression.
      These results highlight differential phenotypic and functional immunosuppressive
      M-MDSC subsets in a retroviral immunodeficiency model. 

PMID- 26318249
TI  - The human papillomavirus 16 European-T350G E6 variant can immortalize but not
      transform keratinocytes in the absence of E7.
AB  - Human papillomavirus type 16 is commonly implicated in HPV-related cancers.
      However, only a small number of infected individuals progress to this stage.
      Epidemiological evidence demonstrated that oncogenic risk is population-specific
      and variations within the viral oncogene, E6, have been suggested to play a role
      in these findings. Of focus in this study is the European-T350G variant, which is
      characterized by an L>V amino acid substitution at residue 83 of the prototype E6
      protein. To elucidate the functional effects of this polymorphism, we followed
      keratinocytes transduced with E-T350G E6 for over 60 passages and compared them
      to keratinocytes transduced, in parallel, with prototype or Asian-American
      (Q14H/L83V/H78Y) E6. We found that although E-T350G E6 immortalized transduced
      keratinocytes in the absence of E7, these cells were not fully transformed. We
      also found that E-T350G down-regulated E-cadherin compared to the other variants,
      providing a possible link between its population-based oncogenicity and host
      genetic variations. 

PMID- 26318250
TI  - [Research in primary care].

PMID- 26318252
TI  - [Need for the gender perspective in the Anales de Pediatria yearbook. Author's
      response].

PMID- 26318251
TI  - [Response to the letter to the editor from SEOP as regards the SEIP-SERPE-SEOP
      consensus document on the treatment of uncomplicated acute osteomyelitis and
      septic arthritis].

PMID- 26318253
TI  - Asparagine Synthetase Deficiency causes reduced proliferation of cells under
      conditions of limited asparagine.
AB  - Asparagine Synthetase Deficiency is a recently described cause of profound
      intellectual disability, marked progressive cerebral atrophy and variable seizure
      disorder. To date there has been limited functional data explaining the
      underlying pathophysiology. We report a new case with compound heterozygous
      mutations in the ASNS gene (NM_183356.3:c. [866G>C]; [1010C>T]). Both variants
      alter evolutionarily conserved amino acids and were predicted to be pathogenic
      based on in silico protein modelling that suggests disruption of the critical ATP
      binding site of the ASNS enzyme. In patient fibroblasts, ASNS expression as well
      as protein and mRNA stability are not affected by these variants. However, there
      is markedly reduced proliferation of patient fibroblasts when cultured in
      asparagine-limited growth medium, compared to parental and wild type fibroblasts.
      Restricting asparagine replicates the physiology within the blood-brain-barrier,
      with limited transfer of dietary derived asparagine, resulting in reliance of
      neuronal cells on intracellular asparagine synthesis by the ASNS enzyme. These
      functional studies offer insight into the underlying pathophysiology of the
      dramatic progressive cerebral atrophy associated with Asparagine Synthetase
      Deficiency. 

PMID- 26318255
TI  - The role of toll-like and protease-activated receptors in the expression of
      cytokines by gingival fibroblasts stimulated with the periodontal pathogen
      Porphyromonas gingivalis.
AB  - Porphyromonas gingivalis is a periodontitis-associated pathogen and interactions
      between the bacterium and gingival fibroblasts play an important role in
      development and progression of periodontitis, an inflammatory disease leading to
      degeneration of tooth-supporting structures. Gingival fibroblasts, which
      expresses protease activated receptors (PARs) as well as toll-like receptors
      (TLRs), produces inflammatory mediators upon bacterial challenges. In this study,
      we elucidated the importance of PAR1, PAR2, TLR2 and TLR4 for the expression and
      secretion of CXCL8, interleukin-6 (IL-6), transforming growth factor-beta1 (TGF
      beta1) and secretory leukocyte inhibitor (SLPI). Human gingival fibroblasts were
      transfected with small-interfering RNA against the target genes, and then
      stimulated with P. gingivalis wild-type W50 and W50-derived double rgp mutant E8
      and kgp mutant K1A. TLR2-silencing reduced P. gingivalis-induced CXCL8 and IL-6.
      IL-6 was also reduced after PAR1-silencing. No effects were observed for TGF
      beta1. SLPI was suppressed by P. gingivalis and silencing of PAR1 as well as
      TLR2, gave additional suppression at the mRNA level. TLR4 was not involved in the
      regulation of the investigated mediators. CXCL8 and IL-6 are important for
      progression and development of periodontitis, leading to a chronic inflammation
      that may contribute to the tissue destruction that follows an exacerbated host
      response. Therefore, regulating the expression of TLR2 and subsequent release of
      CXCL8 and IL-6 in periodontitis could attenuate the tissue destruction seen in
      periodontitis. 

PMID- 26318254
TI  - Verproside inhibits TNF-alpha-induced MUC5AC expression through suppression of
      the TNF-alpha/NF-kappaB pathway in human airway epithelial cells.
AB  - Airway mucus secretion is an essential innate immune response for host
      protection. However, overproduction and hypersecretion of mucus, mainly composed
      of MUC5AC, are significant risk factors in asthma and chronic obstructive
      pulmonary disease (COPD) patients. Previously, we reported that verproside, a
      catalpol derivative iridoid glycoside isolated from Pseudolysimachion rotundum
      var. subintegrum, is a potent anti-asthmatic candidate drug in vivo. However, the
      molecular mechanisms underlying the pharmacological actions of verproside remain
      unknown. Here, we found that verproside significantly reduces the expression
      levels of tumor necrosis factor alpha (TNF-alpha)-induced MUC5AC mRNA and protein
      by inhibiting both nuclear factor kappa B (NF-kappaB) transcriptional activity
      and the phosphorylation of its upstream effectors such as IkappaB kinase
      (IKK)beta, IkappaBalpha, and TGF-beta-activated kinase 1 (TAK1) in NCI-H292
      cells. Moreover, verproside attenuated TNF-alpha-induced MUC5AC transcription
      more effectively when combined with an IKK (BAY11-7082) or a TAK1 (5z-7
      oxozeaenol) inhibitor than when administered alone. Importantly, we demonstrated
      that verproside negatively modulates the formation of the TNF-alpha-receptor
      (TNFR) 1 signaling complex [TNF-RSC; TNFR1-recruited TNFR1-associated death
      domain protein (TRADD), TNFR-associated factor 2 (TRAF2), receptor-interacting
      protein kinase 1 (RIP1), and TAK1], the most upstream signaling factor of NF
      kappaB signaling. In silico molecular docking studies show that verproside binds
      between TRADD and TRAF2 subunits. Altogether, these results suggest that
      verproside could be a good therapeutic candidate for treatment of inflammatory
      airway diseases such as asthma and COPD by blocking the TNF-alpha/NF-kappaB
      signaling pathway. 

PMID- 26318256
TI  - Recycling of waste automotive laminated glass and valorization of polyvinyl
      butyral through mechanochemical separation.
AB  - Due to strong binding, optical clarity, adhesion to many surfaces, toughness and
      flexibility polyvinyl butyral (PVB) resin films are commonly used in the
      automotive and architectural application as a protective interlayer in the
      laminated glass. Worldwide million tons of PVB waste generated from end-of-life
      automotive associated with various environmental issues. Stringent environmental
      directive, higher land cost eliminates land filling option, needs a study, we
      have developed a mechanochemical separation process to separate PVB resins from
      glass and characterized the separated PVB through various techniques, i.e.,
      scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDS),
      infrared spectroscopy (IR) and nuclear magnetic resonance spectroscopy (NMR).
      Commercial nonionic surfactants D201 used for the mechanochemical separation
      purpose. Through parameter optimization following conditions are considered to be
      the optimum condition; 30v ol% D201, stirring speed of 400 rpm, 35  degrees C
      temperature, operation time 1h, and dilute D201 volume to waste automotive
      laminated glass weight ratio of ~25. The technology developed in our laboratory
      is sustainable, environmentally friendly, techno-economical feasible process,
      capable of mass production (recycling).

PMID- 26318257
TI  - Area-level socioeconomic deprivation, nitrogen dioxide exposure, and term birth
      weight in New York City.
AB  - Numerous studies have linked air pollution with adverse birth outcomes, but
      relatively few have examined differential associations across the socioeconomic
      gradient. To evaluate interaction effects of gestational nitrogen dioxide (NO2)
      and area-level socioeconomic deprivation on fetal growth, we used: (1) highly
      spatially-resolved air pollution data from the New York City Community Air Survey
      (NYCCAS); and (2) spatially-stratified principle component analysis of census
      variables previously associated with birth outcomes to define area-level
      deprivation. New York City (NYC) hospital birth records for years 2008-2010 were
      restricted to full-term, singleton births to non-smoking mothers (n=243,853). We
      used generalized additive mixed models to examine the potentially non-linear
      interaction of nitrogen dioxide (NO2) and deprivation categories on birth weight
      (and estimated linear associations, for comparison), adjusting for individual
      level socio-demographic characteristics and sensitivity testing adjustment for co
      pollutant exposures. Estimated NO2 exposures were highest, and most varying,
      among mothers residing in the most-affluent census tracts, and lowest among
      mothers residing in mid-range deprivation tracts. In non-linear models, we found
      an inverse association between NO2 and birth weight in the least-deprived and
      most-deprived areas (p-values<0.001 and 0.05, respectively) but no association in
      the mid-range of deprivation (p=0.8). Likewise, in linear models, a 10 ppb
      increase in NO2 was associated with a decrease in birth weight among mothers in
      the least-deprived and most-deprived areas of -16.2g (95% CI: -21.9 to -10.5) and
      -11.0 g (95% CI: -22.8 to 0.9), respectively, and a non-significant change in the
      mid-range areas [beta=0.5 g (95% CI: -7.7 to 8.7)]. Linear slopes in the most-
      and least-deprived quartiles differed from the mid-range (reference group) (p
      values<0.001 and 0.09, respectively). The complex patterning in air pollution
      exposure and deprivation in NYC, however, precludes simple interpretation of
      interactive effects on birth weight, and highlights the importance of considering
      differential distributions of air pollution concentrations, and potential
      differences in susceptibility, across deprivation levels.

PMID- 26318258
TI  - Serum and adipose tissue as matrices for assessment of exposure to persistent
      organic pollutants in breast cancer patients.
AB  - The aim of this study was to assess differences between two biological matrices
      (serum and breast adipose tissue) in the evaluation of persistent organic
      pollutant (POP) exposure in breast cancer patients. The study population
      consisted of 103 women undergoing surgery for newly diagnosed breast carcinoma in
      a public hospital in Granada, Southern Spain. Independent variables were gathered
      from questionnaires and clinical records. POP concentrations were quantified in
      breast adipose tissue and serum samples. Spearman correlation tests were
      performed between pairs of POP concentrations and stepwise multivariable linear
      regression analyses were conducted to assess predictors of concentrations in the
      two matrices. p,p'- Dichlorodiphenyldichloroethylene (p,p'-DDE) showed the the
      highest median concentration in both matrices (194.34 and 173.84 ng/g lipid in
      adipose tissue and serum, respectively). Median wet-basis adipose tissue:serum
      ratios ranged from 109.34 to 651.62, while lipid-basis ratios ranged from 0.88 to
      4.34. In general, we found significant positive correlation coefficients between
      pairs of POPs in adipose tissue and in serum, which were always higher in adipose
      tissue. We found positive and statistically significant correlations between
      serum and adipose tissue concentrations of p,p'-DDE and hexachlorobenzene (HCB)
      but not of polychlorinated biphenyls (PCBs). Age was positively associated with
      most POPs in adipose tissue and serum, while the body mass index was positively
      associated with adipose tissue HCB concentrations and negatively associated with
      serum PCB-153 and PCB-138 concentrations. Recent weight loss was inversely
      associated with POP residues in adipose tissue and positively associated with POP
      residues in serum. Serum HCB and PCB-180 concentrations were lower in patients
      who had received preoperative chemotherapy. According to our results, serum and
      adipose tissue POP concentrations in breast cancer patients may be differentially
      affected by external predictors. Taken together, these findings indicate the need
      to take account of the individual POP(s) under study and the biological matrix
      used when relating internal POP exposure to breast cancer disease and to make a
      careful selection of covariates for adjusting the model.

PMID- 26318260
TI  - Does human papillomavirus-negative condylomata exist?
AB  - Condylomata acuminata is caused by human papillomavirus (HPV). PCR with consensus
      primers will typically detect HPV in >96% of condylomata. Metagenomic sequencing
      has found that some "HPV-negative" condylomata do indeed contain HPV. We wished
      to perform a renewed evaluation of the "HPV-negative" condylomata using deeper
      metagenomics sequencing. Sequencing of whole genome amplified DNA from 40
      apparently "HPV-negative" condylomata detected HPV in 37/40 specimens. We found
      75 different HPV types, out of which 43 represented novel putative HPV types.
      Three types were cloned and established as HPV types 200, 201 and 202. Molluscum
      contagiosum virus was detected in 24 of the 40 samples. In summary, deep
      sequencing enables detection of HPV in almost all condylomata. "HPV-negative"
      condylomata might largely be explained by clinical misdiagnosis or the presence
      of viral variants, distantly related HPV types and/or low viral loads. 

PMID- 26318259
TI  - Stop-codon and C-terminal nonsense mutations are associated with a lower risk of
      cardiac events in patients with long QT syndrome type 1.
AB  - BACKGROUND: In long QT syndrome type 1 (LQT1), the location and type of mutations
      have been shown to affect the clinical outcome. Although haploinsufficiency,
      including stop-codon and frameshift mutations, has been associated with a lower
      risk of cardiac events in patients with LQT1, nonsense mutations have been
      presumed functionally equivalent. OBJECTIVE: The purpose of this study was to
      evaluate clinical differences between patients with nonsense mutations. METHODS:
      The study sample comprised 1090 patients with genetically confirmed mutations.
      Patients were categorized into 5 groups, depending on mutation type and location:
      missense not located in the high-risk cytoplasmic loop (c-loop) (n = 698), which
      is used as reference; missense c-loop (n = 192); stop-codon (n = 67); frameshift
      (n = 39); and others (n = 94). The primary outcome was a composite end point of
      syncope, aborted cardiac arrest, and long QT syndrome-related death (cardiac
      events). Outcomes were evaluated using the multivariate Cox proportional hazards
      regression analysis. Standard patch clamp techniques were used. RESULTS: Compared
      to patients with missense non-c-loop mutations, the risk of cardiac events was
      reduced significantly in patients with stop-codon mutations (hazard ratio [HR]
      0.57; 95% confidence interval [CI] 0.34-0.96; P = .035), but not in patients with
      frameshift mutations (HR 1.01; 95% CI 0.58-1.77; P = .97). Our data suggest that
      currents of the most common stop-codon mutant channel (Q530X) were larger than
      those of haploinsufficient channels (wild type: 42 +/- 6 pA/pF, n = 20;
      Q530X+wild type: 79 +/- 14 pA/pF, n = 20; P < .05) and voltage dependence of
      activation was altered. CONCLUSION: Stop-codon mutations are associated with a
      lower risk of cardiac events in patients with LQT1, while frameshift mutations
      are associated with the same risk as the majority of the missense mutations. Our
      data indicate functional differences between these previously considered
      equivalent mutation subtypes.

PMID- 26318261
TI  - Human cytomegalovirus induces a distinct innate immune response in the maternal
      fetal interface.
AB  - The initial interplay between human cytomegalovirus (HCMV) and innate tissue
      response in the human maternal-fetal interface, though crucial for determining
      the outcome of congenital HCMV infection, has remained unknown. We studied the
      innate response to HCMV within the milieu of the human decidua, the maternal
      aspect of the maternal-fetal interface, maintained ex vivo as an integral tissue.
      HCMV infection triggered a rapid and robust decidual-tissue innate immune
      response predominated by interferon (IFN)gamma and IP-10 induction, dysregulating
      the decidual cytokine/chemokine environment in a distinctive fashion. The
      decidual-tissue response was already elicited during viral-tissue contact, and
      was not affected by neutralizing HCMV antibodies. Of note, IFNgamma induction,
      reflecting immune-cell activation, was distinctive to the maternal decidua, and
      was not observed in concomitantly-infected placental (fetal) villi. Our studies
      in a clinically-relevant surrogate human model, provide a novel insight into the
      first-line decidual tissue response which could affect the outcome of congenital
      infection. 

PMID- 26318262
TI  - High detection rate of Rickettsia africae in Amblyomma variegatum but low
      prevalence of anti-rickettsial antibodies in healthy pregnant women in
      Madagascar.
AB  - Tick-borne spotted fever group (SFG) rickettsioses are emerging infectious
      diseases in Sub-Saharan Africa. In Madagascar, the endemicity of tick-borne
      rickettsiae and their vectors has been incompletely studied. The first part of
      the present study was conducted in 2011 and 2012 to identify potential
      anthropophilic tick vectors for SFG rickettsiae on cattle from seven Malagasy
      regions, and to detect and characterize rickettsiae in these ticks. Amblyomma
      variegatum was the only anthropophilic tick species found on 262 cattle. Using a
      novel ompB-specific qPCR, screening for rickettsial DNA was performed on 111 A.
      variegatum ticks. Rickettsial DNA was detected in 96 of 111 ticks studied
      (86.5%). Rickettsia africae was identified as the only infecting rickettsia using
      phylogenetic analysis of ompA and ompB gene sequences and three variable
      intergenic spacers from 11 ticks. The second part of the study was a cross
      sectional survey for antibodies against SFG rickettsiae in plasma samples taken
      from healthy, pregnant women at six locations in Madagascar, two at sea level and
      four between 450 and 1300m altitude. An indirect fluorescent antibody test with
      Rickettsia conorii as surrogate SFG rickettsial antigen was used. We found R.
      conorii-seropositives at all altitudes with prevalences between 0.5% and 3.1%.
      Our results suggest that A. variegatum ticks highly infected with R. africae are
      the most prevalent cattle-associated tick vectors for SFG rickettsiosis in
      Madagascar. Transmission of SFG rickettsiosis to humans occurs at different
      altitudes in Madagascar and should be considered as a relevant cause of febrile
      diseases. 

PMID- 26318263
TI  - Relatively low prevalence of Babesia microti and Anaplasma phagocytophilum in
      Ixodes scapularis ticks collected in the Lehigh Valley region of eastern
      Pennsylvania.
AB  - Several human pathogens are transmitted by the blacklegged tick, Ixodes
      scapularis. These include the spirochetes that cause Lyme disease (Borrelia
      burgdorferi) which is endemic to the Lehigh Valley region of eastern
      Pennsylvania. Emerging and currently rare tick-borne diseases have been of
      increasing concern in this region, including tick-borne relapsing fever (caused
      by Borrelia miyamotoi), human granulocytic anaplasmosis (caused by Anaplasma
      phagocytophilum), and human babesiosis (caused by Babesia microti). Real-time PCR
      assays and in some instances, conventional PCR followed by DNA sequencing, were
      used to screen 423 DNA samples that were prepared from questing adult and nymph
      stage I. scapularis ticks for infection with four tick-borne human pathogens. B.
      burgdorferi was detected in 23.2% of the sampled ticks, while B. miyamotoi, B.
      microti and a human variant of A. phagocytophilum were detected in less than 0.5%
      of the ticks. Our results are consistent with those expected in a region where
      Lyme disease is prevalent and human cases of tick-borne relapsing fever,
      babesiosis and human granulocytic anaplasmosis are not currently widespread. It
      is expected that this study will serve as a baseline for future studies of tick
      borne pathogens in an area that is in close proximity to regions of high
      endemicity for Lyme disease, human granulocytic anaplasmosis and human
      babesiosis. 

PMID- 26318264
TI  - Low genetic diversity of Anaplasma marginale in calves in an endemic area for
      bovine anaplasmosis in the state of Sao Paulo, Brazil.
AB  - Major surface protein 1a has been used as a marker for genetic stability in
      identifying geographical isolates of Anaplasma marginale. We conducted a
      longitudinal study to ascertain the genetic diversity of A. marginale in a dairy
      cattle herd with a history of clinical anaplasmosis. A total of 20 calves were
      evaluated every 3 months, from birth to 1 year of age. They were evaluated using
      blood smears, IFAT, ELISA, and qPCR. Additionally, samples positive for the msp1a
      gene using nPCR were sequenced. The detection of A. marginale ranged from 20 to
      90% using blood smears, 20-80% using ELISA/IFAT, and 15-100% using qPCR. We found
      evidence that suggested transplacental transmission of A. marginale in 15% (3/20)
      of the calves based on qPCR and 20% (4/20) based on blood smears. Additionally,
      these four animals were A. marginale ELISA/IFAT-positive. The A. marginale
      strains found were alpha-beta(3)-Gamma (n=7), alpha-beta(2) (n=1), and alpha
      beta(2)-190-Gamma (n=1). The new MSP1a tandem repeat 190 was described. The
      results showed that the genetic diversity of A. marginale in a group of calves up
      to 1 year of age from Taiacu (SP) was low, with only three different strains
      identified, showing the microsatellite genotype E. Eighty percent of the animals
      evaluated had clinical signs of bovine anaplasmosis and were treated using
      oxytetracycline and imidocarb dipropionate. Additionally, it was found that 30%
      (6/20) and 10% (2/20) of the animals required a second and third treatment,
      respectively, based on clinical signs. Four animals infected with the alpha
      beta(3)-Gamma strain died, showing that this strain is also involved in the
      clinical anaplasmosis cases in Brazil. 

PMID- 26318266
TI  - The effects of baicalein and baicalin on mitochondrial function and dynamics: A
      review.
AB  - Mitochondria play an essential role in cell survival by providing energy, calcium
      buffering, and regulating apoptosis. A growing body of evidence shows that
      mitochondrial dysfunction and its consequences, including impairment of the
      mitochondrial respiratory chain, excessive generation of reactive oxygen species,
      and excitotoxicity, play a pivotal role in the pathogenesis of different diseases
      such as neurodegenerative diseases, neuropsychiatric disorders, and cancer. The
      therapeutical role of flavonoids on these diseases is gaining increasing
      acceptance. Numerous studies on experimental models have revealed the favorable
      role of flavonoids on mitochondrial function and structure. This review
      highlights the promising role of baicalin and its aglycone form, baicalein, on
      mitochondrial function and structure with a focus on its therapeutic effects. We
      also discuss their chemistry, sources and bioavailability. 

PMID- 26318265
TI  - Impacts of dance on non-motor symptoms, participation, and quality of life in
      Parkinson disease and healthy older adults.
AB  - Evidence indicates exercise is beneficial for motor and non-motor function in
      older adults and people with chronic diseases including Parkinson disease (PD).
      Dance may be a relevant form of exercise in PD and older adults due to social
      factors and accessibility. People with PD experience motor and non-motor
      symptoms, but treatments, interventions, and assessments often focus more on
      motor symptoms. Similar non-motor symptoms also occur in older adults. While it
      is well-known that dance may improve motor outcomes, it is less clear how dance
      affects non-motor symptoms. This review aims to describe the effects of dance
      interventions on non-motor symptoms in older adults and PD, highlights
      limitations of the literature, and identifies opportunities for future research.
      Overall, intervention parameters, study designs, and outcome measures differ
      widely, limiting comparisons across studies. Results are mixed in both
      populations, but evidence supports the potential for dance to improve mood,
      cognition, and quality of life in PD and healthy older adults. Participation and
      non-motor symptoms like sleep disturbances, pain, and fatigue have not been
      measured in older adults. Additional well-designed studies comparing dance and
      exercise interventions are needed to clarify the effects of dance on non-motor
      function and establish recommendations for these populations.

PMID- 26318267
TI  - A transition towards a healthier global population?

PMID- 26318268
TI  - Predicting suicide attempts in depressed adolescents: Clarifying the role of
      disinhibition and childhood sexual abuse.
AB  - BACKGROUND: Suicide is the second leading cause of death among adolescents, and
      depressed youth are six times more likely to make suicide attempts as compared to
      non-depressed adolescents. The present study examined the unique and interactive
      effects of two well-established correlates of suicidality - childhood sexual
      abuse (CSA) and disinhibition - in predicting suicide attempts among depressed
      adolescents. METHOD: Participants were 163 adolescents (125 females) aged 13-18
      (M=15.60, SD=1.27) diagnosed with Major Depressive Disorder (n=95, 58.3%) and/or
      Dysthymia (n=69, 42.3%) recruited from an acute residential treatment service.
      Participants completed interviews assessing psychopathology and suicidality, self
      report measures of depressive symptoms and CSA, and a computerized disinhibition
      task. RESULTS: Consistent with hypotheses, CSA moderated the association between
      disinhibition and adolescents' report of their past year and lifetime suicide
      attempts. Specifically, higher disinhibition was associated with a greater
      likelihood of having made a suicide attempt among adolescents with a history of
      CSA, but not among those without. The same pattern of results held in analyses of
      suicide attempt frequency. LIMITATIONS: Primary findings were based on
      observational, cross-sectional data, and therefore, causal relationships cannot
      be inferred. The gender imbalance in the sample precluded stratifying our
      analyses by gender. CSA was ascertained by self-report; replication of the
      results with more objective measures is warranted. CONCLUSIONS: Our findings
      indicate that CSA and disinhibition may work together to predict elevated suicide
      risk, and these results have implications for early identification efforts in
      youth at high risk for suicide.

PMID- 26318270
TI  - A review of white matter microstructure alterations of pathways of the reward
      circuit in depression.
AB  - BACKGROUND: Depressed mood, anhedonia, psychomotor retardation and alterations of
      circadian rhythm are core features of the depressive syndrome. Its neural
      correlates can be located within a frontal-striatal-tegmental neural network,
      commonly referred to as the reward circuit. It is the aim of this article to
      review literature on white matter microstructure alterations of the reward system
      in depression. METHOD: We searched for diffusion tensor imaging (DTI)-studies
      that have explored neural deficits within the cingulum bundle, the uncinate
      fasciculus and the supero-lateral medial forebrain bundle/anterior thalamic
      radiation - in adolescent and adult depression (acute and remitted), melancholic
      depression, treatment-resistant depression and those at familial risk of
      depression. The relevant diffusion MRI literature was identified using PUBMED.
      RESULTS: Thirty-five studies were included. In people at familial risk for
      depression the main finding was reduced fractional anisotropy (FA) in the
      cingulum bundle. Both increases and decreases of FA have been reported in the
      uncinate fasciculus in adolescents. Reductions of FA in the uncinate fasciculus
      and the anterior thalamic radiation/supero-lateral medial forebrain bundle during
      acute depressive episodes in adults were most consistently reported. LIMITATIONS:
      Non-quantitative approach. CONCLUSIONS: Altered cingulum bundle microstructure in
      unaffected relatives may either indicate resilience or vulnerability to
      depression. Uncinate fasciculus and supero-lateral medial forebrain bundle
      microstructure may be altered during depressive episodes in adult MDD. Future
      studies call for a careful clinical stratification of clinically meaningful
      subgroups.

PMID- 26318269
TI  - Symptom course in inpatient and day clinic treatment of depression: Results from
      the INDDEP-Study.
AB  - BACKGROUND: In major depression (MDD), hospital treatment is an option in more
      severe cases or if outpatient treatment failed. Psychosomatic hospitals in
      Germany provide treatment programs with multimodal psychotherapy, either in an
      inpatient or a day hospital setting. In the context of health care research, this
      study aimed (1) to compare characteristics of patients treated in psychosomatic
      day hospitals and inpatient units, (2) to compare the effectiveness of both
      treatment modalities. METHODS: A naturalistic design was chosen to achieve
      external validity. 604 consecutive patients were assessed at admission, discharge
      and a 3-month follow-up. Primary outcome was defined as a reduction of depressive
      symptomatology (QIDS-C), secondary outcomes comprise overall functioning and
      quality of life. For a comparison of effectiveness, inpatient and day hospital
      samples were matched according to known predictors of outcome. RESULTS: The few
      differences found between the inpatient and day hospital sample were related to
      severity of depression and physical impairment. Inpatients more often got
      antidepressant medication. Additionally, inpatients were treated significantly
      longer, due to a subgroup of patients with somatic co-morbidity. There were no
      differences when comparing effectiveness. LIMITATIONS: When comparing treatment
      effectiveness, possible bias cannot be ruled out. There was no randomization or
      untreated control group. CONCLUSIONS: In patients with a more severe depression
      and somatic co-morbidity, inpatient treatment might be preferred as compared to
      day hospital treatment. However, most patients can be treated in both settings.

PMID- 26318271
TI  - Adding mindfulness-based cognitive therapy to maintenance antidepressant
      medication for prevention of relapse/recurrence in major depressive disorder:
      Randomised controlled trial.
AB  - BACKGROUND: Mindfulness-based cognitive therapy (MBCT) and maintenance
      antidepressant medication (mADM) both reduce the risk of relapse in recurrent
      depression, but their combination has not been studied. Our aim was to
      investigate whether the addition of MBCT to mADM is a more effective prevention
      strategy than mADM alone. METHODS: This study is one of two multicenter
      randomised trials comparing the combination of MBCT and mADM to either
      intervention on its own. In the current trial, recurrently depressed patients in
      remission who had been using mADM for 6 months or longer (n=68), were randomly
      allocated to either MBCT+mADM (n=33) or mADM alone (n=35). Primary outcome was
      depressive relapse/recurrence within 15 months. Key secondary outcomes were time
      to relapse/recurrence and depression severity. Analyses were based on intention
      to-treat. RESULTS: There were no significant differences between the groups on
      any of the outcome measures. LIMITATIONS: The current study included patients who
      had recovered from depression with mADM and who preferred the certainty of
      continuing medication to the possibility of participating in MBCT. Lower
      expectations of mindfulness in the current trial, compared with the parallel
      trial, may have caused selection bias. In addition, recruitment was hampered by
      the increasing availability of MBCT in the Netherlands, and even about a quarter
      of participants included in the trial who were allocated to the control group
      chose to get MBCT elsewhere. CONCLUSIONS: For this selection of recurrently
      depressed patients in remission and using mADM for 6 months or longer, MBCT did
      not further reduce their risk for relapse/recurrence or their (residual)
      depressive symptoms.

PMID- 26318272
TI  - Predictive factors for prolonged remission after autologous hematopoietic stem
      cell transplantation in young patients with type 1 diabetes mellitus.
AB  - BACKGROUND AIMS: Autologous hematopoietic stem cell transplantation (auto-HSCT)
      followed by immunoablation is a promising therapy for type 1 diabetes mellitus
      (T1DM) treatment due to the immunosuppression and immunomodulation mechanisms.
      Indeed, a considerable number of patients have been able to discontinue insulin
      use with this treatment. However, nonresponse and relapse occur after auto-HSCT.
      It is important to select the patients who can potentially benefit from this
      treatment, but the factors that might influence the therapeutic outcome are
      unclear. The objective of this study was to explore the predictors for prolonged
      remission after auto-HSCT therapy. METHODS: The data for this study were
      extracted from an open-label prospective study, which was performed to treat new
      onset T1DM patients with auto-HSCT. The 128 patients were categorized into
      insulin-free (IF) or insulin-dependent (ID) groups according to their response to
      treatment during the follow-up. We compared the baseline data of the two groups
      and explored possible prognostic factors and their odd ratios (ORs) with
      univariate analysis and multivariate logistic regression. Receiver operating
      characteristic curves (ROC) were performed to test the model discrimination
      function. RESULTS: During a follow-up of 28.5 +/- 8.3 months, 71 of 128 patients
      in the IF group discontinued insulin use, whereas 57 of 128 patients in the ID
      group did not decrease their insulin dose or resumed insulin treatment after a
      transient remission. Multivariate logistic regression analysis demonstrated that
      prolonged remission was positively correlated with fasting C-peptide level (OR =
      2.60, 95% confidence interval [CI]: 1.16-5.85) but negatively correlated with
      onset age (OR = 0.36, 95% CI: 0.14-0.88) and tumor necrosis factor-alpha levels
      (OR = 0.32, 95% CI: 0.14-0.73). ROC analysis confirmed the combined predictive
      function of these three variables (AUC = 0.739, 95% CI: 0.655-0.824).
      CONCLUSIONS: Age and fasting C-peptide and tumor necrosis factor-alpha levels
      were identified as possible predictors for prolonged remission following auto
      HSCT therapy.

PMID- 26318273
TI  - Ammonia impairs glutamatergic communication in astroglial cells: protective role
      of resveratrol.
AB  - Ammonia is a key toxin in the precipitation of hepatic encephalopathy (HE), a
      neuropsychiatric disorder associated with liver failure. In response to ammonia,
      various toxic events are triggered in astroglial cells, and alterations in brain
      glutamate communication are common. Resveratrol is a polyphenolic compound that
      has been extensively studied in pathological events because it presents several
      beneficial effects, including some in the central nervous system (CNS). We
      previously described that resveratrol is able to significantly modulate glial
      functioning and has a protective effect during ammonia challenge in vitro. In
      this study, we addressed the mechanisms by which resveratrol can protect C6
      astroglial cells from glutamatergic alterations induced by ammonia. Resveratrol
      was able to prevent all the effects triggered by ammonia: (i) decrease in
      glutamate uptake activity and expression of the EAAC1 glutamate transporter, the
      main glutamate transporter present in C6 cells; (ii) increase of glutamate
      release, which was also dependent on the activation of the Na(+)-K(+)-Cl(-) co
      transporter NKCC1; (iii) reduction in GS activity and intracellular GSH content;
      and (iv) impairment of Na(+)K(+)-ATPase activity. Interestingly, resveratrol, per
      se, also positively modulated the astroglial functions evaluated. Moreover, we
      demonstrated that heme oxygenase 1 (HO1), an enzyme that is part of the cellular
      defense system, mediated some of the effects of resveratrol. In conclusion, the
      mechanisms of the putative protective role of resveratrol against ammonia
      toxicity involve the modulation of pathways and molecules related to glutamate
      communication in astroglial cells. 

PMID- 26318275
TI  - Metabolomics analysis of the toxicity pathways of triphenyl phosphate in HepaRG
      cells and comparison to oxidative stress mechanisms caused by acetaminophen.
AB  - Since the publication of REACH guidelines, the need for in vitro tools for
      toxicity testing has increased. We present here the development of a
      hepatotoxicity testing tool using human HepaRG cell cultures and metabolomics.
      HepaRG cells were exposed to either 4mM acetaminophen (APAP) as reference
      toxicant for oxidative stress or 50 MUM triphenyl phosphate (TPHP) as toxicant
      with unknown toxicity pathways (TPs). After 72 h exposure, cells were subjected
      to quenching and liquid-liquid extraction which resulted in a polar and an apolar
      fraction. Analysis of fractions was performed by ultrahigh performance liquid
      chromatography-high resolution tandem mass spectrometry (UHPLC-QTOF-MS).
      Significantly up or down regulated metabolites were selected by univariate
      statistics prior to identification. In order to obtain robust and specific TP
      biomarkers, the experiment was also repeated using a different culture medium
      composition to assess which metabolites show consistent changes. Potential
      biomarkers belonging to different TPs were found for APAP and TPHP. For APAP, the
      biomarkers were related to a decrease in unsaturated phospholipids, and for TPHP
      to an accumulation of phosphoglycerolipids and increase of palmitoyl
      lysophosphatidylcholine. This first proof-of-concept opens new perspectives for
      the analysis of other (reference) toxicants with different TPs and it can be used
      to expand the in vitro tool for hepatotoxicity screening of various compounds.

PMID- 26318274
TI  - The brominated flame retardants TBP-AE and TBP-DBPE antagonize the chicken
      androgen receptor and act as potential endocrine disrupters in chicken LMH cells.
AB  - Increased exposure of birds to endocrine disrupting compounds has resulted in
      developmental and reproductive dysfunctions. We have recently identified the
      flame retardants, allyl-2,4,6-tribromophenyl ether (TBP-AE), 2-3-dibromopropyl
      2,4,6-tribromophenyl ether (TBP-DBPE) and the TBP-DBPE metabolite 2-bromoallyl
      2,4,6-tribromophenyl ether (TBP-BAE) as antagonists to both the human androgen
      receptor (AR) and the zebrafish AR. In the present study, we aimed at determining
      whether these compounds also interact with the chicken AR. In silico modeling
      studies showed that TBP-AE, TBP-BAE and TBP-DBPE were able to dock into to the
      chicken AR ligand-binding pocket. In vitro transfection assays revealed that all
      three brominated compounds acted as chicken AR antagonists, inhibiting
      testosterone induced AR activation. In addition, qRT-PCR studies confirmed that
      they act as AR antagonists and demonstrated that they also alter gene expression
      patterns of apoptotic, anti-apoptotic, drug metabolizing and amino acid
      transporter genes. These studies, using chicken LMH cells, suggest that TBP-AE,
      TBP-BAE and TBP-DBPE are potential endocrine disrupters in chicken. 

PMID- 26318276
TI  - Concerns in the application of fluorescent probes DCDHF-DA, DHR 123 and DHE to
      measure reactive oxygen species in vitro.
AB  - Reactive oxygen species (ROS) are formed in biological systems by partial
      reduction of molecular oxygen. The essential role of ROS in maintaining
      physiological health may be corrupted into oxidative stress by their
      overproduction or the exhaustion of antioxidant mechanisms. Many studies covering
      a broad range of methodologies have investigated ROS production and their toxic
      mechanisms of action. Of these methodologies, fluorometry has been among the
      preferred techniques. Three frequently used fluorescent probes for in vitro
      studies are 2',7'-dichlorodihydrofluorescein diacetate (DCDHF-DA),
      Dihydrorhodamine 123 (DHR 123) and Dihydroethidium (DHE). Apart from the
      unavoidable limitations of auto-oxidation, photo-oxidation and photo-conversion,
      there are also concerns relating to protocol modification for the improved
      monitoring of ROS. This paper aims to highlight such contributing factors,
      including cell culture conditions and the characteristics of individual
      fluorescent probes in the utilization of these selected probes in in vitro
      systems.

PMID- 26318277
TI  - Diabetes and chronic kidney disease.

PMID- 26318278
TI  - Mexican propolis flavonoids affect photosynthesis and seedling growth.
AB  - As a continuous effort to find new natural products with potential herbicide
      activity, flavonoids acacetin (1), chrysin (2) and 4',7-dimethylnarangenin (3)
      were isolated from a propolis sample collected in the rural area of Mexico City
      and their effects on the photosynthesis light reactions and on the growth of
      Lolium perenne, Echinochloa crus-galli and Physalis ixocarpa seedlings were
      investigated. Acacetin (1) acted as an uncoupler by enhancing the electron
      transport under basal and phosphorylating conditions and the Mg(2+)-ATPase.
      Chrysin (2) at low concentrations behaved as an uncoupler and at concentrations
      up to 100 MUM its behavior was as a Hill reaction inhibitor. Finally, 4',7
      dimethylnarangenin (3) in a concentration-dependent manner behaved as a Hill
      reaction inhibitor. Flavonoids 2 and 3 inhibited the uncoupled photosystem II
      reaction measured from water to 2,5-dichloro-1,4-benzoquinone (DCBQ), and they
      did not inhibit the uncoupled partial reactions measured from water to sodium
      silicomolybdate (SiMo) and from diphenylcarbazide (DPC) to diclorophenol
      indophenol (DCPIP). These results indicated that chrysin and 4',7
      dimethylnarangenin inhibited the acceptor side of PS II. The results were
      corroborated with fluorescence of chlorophyll a measurements. Flavonoids also
      showed activity on the growth of seedlings of Lolium perenne and Echinochloa crus
      galli.

PMID- 26318279
TI  - NaCl-induced physiological and biochemical changes in two cyanobacteria Nostoc
      muscorum and Phormidium foveolarum acclimatized to different photosynthetically
      active radiation.
AB  - The present study is aimed at investigating physiological and biochemical
      behavior of two cyanobacteria Nostoc muscorum and Phormidium foveolarum
      acclimatized to different levels (sub-optimum; 25 +/- 0.5, optimum; 75 +/- 2.5
      and supra-optimum; 225 +/- 3.5 MUmol photons m(-2) s(-1)) of photosynthetic
      active radiation (PAR), and subsequently treated with two doses (30 and 90 mM) of
      NaCl. PAR influences growth in tested cyanobacteria being maximum in supra
      optimum PAR acclimatized cells. NaCl-induced maximum percent decline in growth
      was observed in sub-optimum PAR acclimatized cells, which was in consonance with
      a decrease in chlorophyll content. Sub-optimum PAR acclimatization stimulated
      phycocyanin content in control cells, whereas maximum carotenoids content was
      observed in supra-optimum PAR acclimatized cells. Photosystem II photochemistry
      viz. Fv/F0, Fv/Fm, Psi0, phiE0, PIABS, ABS/RC, TR0/RC, ET0/RC and DI0/RC was also
      influenced by PAR and NaCl. Maximum percent rise in superoxide radical (SOR),
      hydrogen peroxide (H2O2) and lipid peroxidation was observed in sub-optimum PAR
      acclimatized cells exposed to NaCl, which could be correlated with lower values
      of enzymatic (superoxide dismutase, catalase, peroxidase and glutathione-S
      transferase) and non-enzymatic (NP-SH and cysteine) antioxidants. In supra
      optimum PAR acclimatized cells level of oxidative stress markers was in parallel
      with enhanced antioxidants. The results suggest that PAR significantly changes
      physiological and biochemical responses of studied cyanobacteria under NaCl
      stress. Besides this, this study also shows that P. foveolarum is more tolerant
      than N. muscorum under test conditions.

PMID- 26318280
TI  - The phototoxicity of vemurafenib: An investigation of clinical monochromator
      phototesting and in vitro phototoxicity testing.
AB  - BACKGROUND: Vemurafenib is a targeted therapy approved for the treatment of
      patients with metastatic melanoma harbouring the BRAF V600E mutation.
      Photosensitivity has been reported in over 50% of patients and has been
      demonstrated to involve at least the broadband UVA spectrum in most patients.
      Erythrocyte protoporphyrin levels have also been reported as elevated in some
      patients. OBJECTIVES: We report the results of monochromator phototesting in one
      patient recorded before and while taking vemurafenib. Analysis of porphyrin
      levels was also conducted. RESULTS: After one month of vemurafenib therapy the
      patient demonstrated markedly increased light sensitivity in the UVA spectrum
      between 335 +/- 27 nm, 365 +/- 27 nm and 400 +/- 27 nm. However responses in the
      UVB (305 +/- 5 nm) and blue light (430 +/- 27 nm) regions were normal. There was
      no abnormal immediate erythemal response. Pre-vemurafenib baseline phototesting
      was normal, as was repeat testing two months later when the patient was taking
      high doses of systemic steroid. No abnormal porphyrins were detected and the
      antinuclear antibody test was normal. In parallel studies, HaCaT keratinocytes
      incubated with vemurafenib were killed by UVA but not by visible (blue) light and
      did not show evidence of detectable intracellular porphyrin in the presence of
      the drug. CONCLUSION: These data confirm vemurafenib induced UVA photosensitivity
      with a probable phototoxic mechanism not mediated via enhanced porphyrin.

PMID- 26318281
TI  - Mangiferin and naringenin affect the photostability and phototoxicity of
      sunscreens containing avobenzone.
AB  - Efficient UV-absorbing molecules are designed to protect against UV-light
      exposure. However, the development of photostable sunscreens is important to
      preserve the photoprotective efficacy and to prevent the formation of reactive
      oxygen species (ROS) and photodegradation products, which can promote phototoxic
      or photoallergic contact dermatitis. The aim of this study was to evaluate the
      effects of mangiferin and naringenin on the photostability and phototoxicity of
      sunscreens containing avobenzone. Cosmetic sunscreen formulations containing
      octocrylene (OCT), octyl methoxycinnamate (OMC) and avobenzone (AVO) were
      prepared and supplemented or not with mangiferin, naringenin, or with both
      compounds in combination. For photostability studies, samples of the formulations
      were spread onto glass plates, exposed to UVA radiation and then analyzed by high
      performance liquid chromatography (HPLC) to determine UV filters and the
      antioxidants recovery. The phototoxicity of the UV filters and antioxidants was
      evaluated using 3T3 fibroblast cultures that were subjected (or not) to
      irradiation according to OECD TG 432. The photostability studies demonstrated
      that AVO and naringenin showed the highest photodegradation when present in
      formulation FN (containing octocrylene, avobenzone, octyl methoxycinnamate and
      naringenin). The addition of mangiferin to this combination (FMN) resulted in an
      improved photostability of both substances compared to FN. The in vitro
      phototoxicity test showed that only avobenzone was considered phototoxic. The
      combination containing AVO/naringenin exhibited phototoxic potential; however,
      this was reduced by the addition of mangiferin (combination CMN). The results of
      this study are promising because it was demonstrated that mangiferin could
      increase the photostability and reduce the phototoxic potential of the
      combination of naringenin and AVO. 

PMID- 26318282
TI  - Pharmacological investigation of 2-aminobenzothiazolium-4
      methylbenzenesulphonate: Synthesis, spectral characterization and structural
      elucidation.
AB  - An organic charge transfer complex, 2-aminobenzothiazolium-4
      methylbenzenesulphonate (ABPTS) was synthesized and single crystals grown by slow
      solvent evaporation solution growth technique at ambient temperature. The single
      crystal X-ray diffraction analysis was carried out to establish the molecular
      structure of the title crystal. FT-IR spectral study was carried out to identify
      the various functional groups present in the crystal. The (1)H and (13)C spectra
      were recorded to further confirm the molecular structure of the CT complex. The
      TG/DTA analyses were carried out to establish the thermal stability of the
      complex. The antibacterial and antifungal activities of synthesized complex were
      examined against various bacteria and fungi strains, to identify the
      antibacterial and antifungal activity. The DNA binding profile of the complex has
      been investigated through absorption spectroscopy and complex has intrinsic
      binding constant 3.6 * 10(4) M(-1). A gel electrophoresis assay demonstrated the
      ability of the complex to cleave the pBR322 DNA. The free radical scavenging
      activity of the complex has been determined against DPPH, OH and ABTS radicals.

PMID- 26318283
TI  - ZnO/graphite composites and its antibacterial activity at different conditions.
AB  - The paper reports laboratory preparation, characterization and in vitro
      evaluation of antibacterial activity of ZnO/graphite nanocomposites. Zinc
      chloride and sodium carbonate served as precursors for synthesis of zinc oxide,
      while micromilled and natural graphite were used as the matrix for ZnO
      nanoparticles anchoring. During the reaction of ZnCl2 with saturated aqueous
      solution of Na2CO3a new compound is created. During the calcination at the
      temperature of 500  degrees C this new precursors decomposes and ZnO
      nanoparticles are formed. Composites ZnO/graphite with 50 wt.% of ZnO particles
      were prepared. X-ray powder diffraction and Raman microspectroscopy served as
      phase-analytical methods. Scanning electron microscopy technique was used for
      morphology characterization of the prepared samples and EDS mapping for
      visualization of elemental distribution. A developed modification of the standard
      microdilution test was used for in vitro evaluation of daylight induced
      antibacterial activity and antibacterial activity at dark conditions. Common
      human pathogens served as microorganism for antibacterial assay. Antibacterial
      activity of ZnO/graphite composites could be based on photocatalytic reaction;
      however there is a role of Zn(2+) ions on the resulting antibacterial activity
      which proved the experiments in dark condition. There is synergistic effect
      between Zn(2+) caused and reactive oxygen species caused antibacterial activity.

PMID- 26318284
TI  - Activation of AHR mediates the ubiquitination and proteasome degradation of c-Fos
      through the induction of Ubcm4 gene expression.
AB  - The ubiquitin-proteasome system (UPS) is a specific, non-lysosomal pathway
      responsible for the controlled degradation of abnormal and short-half-life
      proteins. Despite its relevance in cell homeostasis, information regarding
      control of the UPS component gene expression is lacking. Data from a recent study
      suggest that the aryl hydrocarbon receptor (AHR), a ligand-dependent
      transcription factor, might control the expression of several genes encoding for
      UPS proteins. Here, we showed that activation of AHR by TCDD and beta
      naphthoflavone (beta-NF) results in Ubcm4 gene induction accompanied by an
      increase in protein levels. UbcM4 is an ubiquitin-conjugating enzyme or E2
      protein that in association with ubiquitin ligase enzymes or E3 ligases promotes
      the ubiquitination and 26S proteasome-mediated degradation of different proteins,
      including p53, c-Myc, and c-Fos. We also present data demonstrating increased c
      Fos ubiquitination and proteasomal degradation through the AHR-mediated induction
      of UbcM4 expression. The present study shows that AHR modulates the degradation
      of proteins involved in cell cycle control, consistent with previous reports
      demonstrating an essential role of the AHR in cell cycle regulation. 

PMID- 26318285
TI  - Iron overload triggers mitochondrial fragmentation via calcineurin-sensitive
      signals in HT-22 hippocampal neuron cells.
AB  - The accumulation of iron in neurons has been proposed to contribute to the
      pathology of numerous neurodegenerative diseases, such as Alzheimer's disease and
      Parkinson's disease. However, insufficient research has been conducted on the
      precise mechanism underlying iron toxicity in neurons. In this study, we
      investigated mitochondrial dynamics in hippocampal HT-22 neurons exposed to
      ferric ammonium citrate (FAC) as a model of iron overload and neurodegeneration.
      Incubation with 150 MUM FAC for 48 h resulted in decreased cell viability and
      apoptotic death in HT-22 cells. The FAC-induced iron overload triggered
      mitochondrial fragmentation, which was accompanied by Drp1(Ser637)
      dephosphorylation. Iron chelation with deferoxamine prevented the FAC-induced
      mitochondrial fragmentation and apoptotic cell death by inhibiting Drp1(Ser637)
      dephosphorylation. In addition, a S637D mutation of Drp1, which resulted in a
      phosphorylation-mimetic form of Drp1 at Ser637, protected against the FAC-induced
      mitochondrial fragmentation and neuronal apoptosis. FK506 and cyclosporine A,
      inhibitors of calcineurin activation, determined that calcineurin was associated
      with the iron-induced changes in mitochondrial morphology and the phosphorylation
      levels of Drp1. These results indicate that the FAC-induced dephosphorylation of
      Drp1-dependent mitochondrial fragmentation was rescued by the inhibition of
      calcineurin activation. Therefore, these findings suggest that calcineurin
      mediated phosphorylation of Drp1(Ser637) acts as a key regulator of neuronal cell
      loss by modulating mitochondrial dynamics in iron-induced toxicity. These results
      may contribute to the development of novel therapies for treatment of
      neurodegenerative disorders related to iron toxicity.

PMID- 26318286
TI  - Hypercholesterolemia aggravates myocardial ischemia reperfusion injury via
      activating endoplasmic reticulum stress-mediated apoptosis.
AB  - The effect of hypercholesterolemia on myocardial ischemia reperfusion injury
      (MIRI) is in controversy and the underlying mechanism is still not well
      understood. In the present study, we firstly detected the effects of
      hypercholesterolemia on MIRI and the role of endoplasmic reticulum (ER) stress
      mediated apoptosis pathway in this process. The infarct size was determined by
      TTC staining, and apoptosis was measured by the TUNEL method. The marker proteins
      of ER stress response and ER stress-mediated apoptosis pathway were detected by
      Western blot. The results showed that high cholesterol diet-induced
      hypercholesterolemia significantly increased the myocardial infarct size, the
      release of myocardium enzyme and the ratio of apoptosis, but did not affect the
      recovery of cardiac function. Moreover, hypercholesterolemia also remarkably up
      regulated the expressions of ER stress markers (glucose-regulated protein 78 and
      calreticulin) and critical molecules in ER stress-mediated apoptosis pathway
      (CHOP, caspase 12, phospho-JNK). In conclusion, our study demonstrated that
      hypercholesterolemia enhanced myocardial vulnerability/sensitivity to ischemia
      reperfusion injury involved in aggravation the ER stress and activation of ER
      stress-mediated apoptosis pathway and it gave us a new insight into the
      underlying mechanisms associated with hypercholesterolemia-induced exaggerated
      MIRI and also provided a novel target for preventing MIRI in the presence of
      hypercholesterolemia. 

PMID- 26318287
TI  - Nonparametric Estimates of Gene * Environment Interaction Using Local Structural
      Equation Modeling.
AB  - Gene * environment (G * E) interaction studies test the hypothesis that the
      strength of genetic influence varies across environmental contexts. Existing
      latent variable methods for estimating G * E interactions in twin and family data
      specify parametric (typically linear) functions for the interaction effect. An
      improper functional form may obscure the underlying shape of the interaction
      effect and may lead to failures to detect a significant interaction. In this
      article, we introduce a novel approach to the behavior genetic toolkit, local
      structural equation modeling (LOSEM). LOSEM is a highly flexible nonparametric
      approach for estimating latent interaction effects across the range of a measured
      moderator. This approach opens up the ability to detect and visualize new forms
      of G * E interaction. We illustrate the approach by using LOSEM to estimate gene
      * socioeconomic status interactions for six cognitive phenotypes. Rather than
      continuously and monotonically varying effects as has been assumed in
      conventional parametric approaches, LOSEM indicated substantial nonlinear shifts
      in genetic variance for several phenotypes. The operating characteristics of
      LOSEM were interrogated through simulation studies where the functional form of
      the interaction effect was known. LOSEM provides a conservative estimate of G * E
      interaction with sufficient power to detect statistically significant G * E
      signal with moderate sample size. We offer recommendations for the application of
      LOSEM and provide scripts for implementing these biometric models in Mplus and in
      OpenMx under R.

PMID- 26318289
TI  - Renal cell carcinoma in functional renal graft: Toward ablative treatments.
AB  - The occurrence of a kidney transplant tumor is a rare but serious issue with a
      double risk: the return to dialysis and the development of metastatic cancer.
      Publications on this topic are mainly case reports. The purpose of this review
      was to report an exhaustive literature review of functional graft renal cell
      carcinomas to highlight the impact of tumors on the renal graft outcomes. 201 de
      novo renal carcinomas in functional renal grafts from 69 publications were
      included. Incidence was estimated at 0.18%. Graft tumors were mostly asymptomatic
      (85.9%). Whatever the discovery circumstances of graft tumors, they were mostly
      documented by graft ultrasounds supplemented by CT-scanning or MR imaging.
      Nephron sparing surgery (95 patients) was the first treatment performed followed
      by radiofrequency ablation (38 patients) and cryotherapy (10 patients). The most
      common tumor graft histology was clear cell carcinoma (46.4%), followed by
      papillary carcinoma (43.7%). Specific mortality was 2.9% with 6 deaths. Renal
      graft cell carcinoma is a rare pathology with a low specific death. When
      possible, conservative treatment should be the first choice. 

PMID- 26318288
TI  - G*E Interaction Influences Trajectories of Hand Grip Strength.
AB  - Age-related decline in grip strength predicts later life disability, frailty,
      lower well-being and cognitive change. While grip strength is heritable, genetic
      influence on change in grip strength has been relatively ignored, with non-shared
      environmental influence identified as the primary contributor in a single
      longitudinal study. The extent to which gene-environment interplay, particularly
      gene-environment interactions, contributes to grip trajectories has yet to be
      examined. We considered longitudinal grip strength measurements in seven twin
      studies of aging in the Interplay of Genes and Environment across Multiple
      Studies consortium. Growth curve parameters were estimated for same-sex pairs,
      aged 34-99 (N = 10,681). Fisher's test for mixture distribution of within
      monozygotic twin-pair differences (N = 1724) was performed on growth curve
      parameters. We observed significant gene-environment interaction on grip strength
      trajectories. Finally, we compared the variability of within-pair differences of
      growth curve parameters by APOE haplotypes. Though not statistically significant,
      the results suggested that APOE E2E2/E2E3 haplotypes might buffer environmental
      influences on grip strength trajectories. 

PMID- 26318290
TI  - Identification of Alzheimer's disease-associated long noncoding RNAs.
AB  - Alzheimer's disease (AD) is the most common dementia among the elderly that
      involves complex neurodegenerative alterations. Multiple cellular processes
      including regulation of amyloid-beta peptide, tau, inflammation, and cell death
      have been suggested to associate with AD, but it remains largely unknown if long
      noncoding RNAs (lncRNAs) may be playing a role in AD pathogenesis. Here, we
      identify AD-associated lncRNAs by reannotation of microarray data based on
      postmortem tissue samples of AD patients and matched elderly controls. We found
      24 upregulated and 84 downregulated lncRNAs in AD patients compared with
      controls, most being intergenic. An analysis of lncRNAs in various tissues
      indicated that most downregulated lncRNAs in AD are highly expressed in the brain
      but not in other tissues. Gene set enrichment analysis identified a downregulated
      lncRNA n341006 in association with protein ubiquitination pathway, and a
      significantly upregulated lncRNA n336934 linked to cholesterol homeostasis.
      Interestingly, lncRNA expression signatures could predict tissue types with equal
      accuracy as protein-coding genes, but the number of lncRNAs required for optimal
      prediction was less than protein-coding genes. Taken together, our study provides
      a resource for AD-associated lncRNAs for the development of lncRNA biomarkers and
      the identification of functional lncRNAs involved in AD pathogenesis. 

PMID- 26318291
TI  - Epithelial derived CTGF promotes breast tumor progression via inducing EMT and
      collagen I fibers deposition.
AB  - Interactions among tumor cells, stromal cells, and extracellular matrix
      compositions are mediated through cytokines during tumor progression. Our
      analysis of 132 known cytokines and growth factors in published clinical breast
      cohorts and our 84 patient-derived xenograft models revealed that the elevated
      connective tissue growth factor (CTGF) in tumor epithelial cells significantly
      correlated with poor clinical prognosis and outcomes. CTGF was able to induce
      tumor cell epithelial-mesenchymal transition (EMT), and promote stroma deposition
      of collagen I fibers to stimulate tumor growth and metastasis. This process was
      mediated through CTGF-tumor necrosis factor receptor I (TNFR1)-IkappaB autocrine
      signaling. Drug treatments targeting CTGF, TNFR1, and IkappaB signaling each
      prohibited the EMT and tumor progression. 

PMID- 26318292
TI  - Metabolic alterations caused by HNF1beta expression in ovarian clear cell
      carcinoma contribute to cell survival.
AB  - HNF1beta is expressed exclusively in ovarian clear cell carcinoma (OCCC) and not
      in other ovarian cancers, regarded as a hallmark of this tumor. This implies its
      central role in the unique character of OCCC, including resistance to
      chemotherapy, but its exact role and influence in cancer biology or the molecular
      bases of its function are largely unknown. Using comprehensive metabolome
      analysis of HNF1beta_shRNA-stable cell lines, we show here that HNF1beta
      drastically alters intracellular metabolism, especially in direction to enhance
      aerobic glycolysis, so called the "Warburg effect". The consequence of the
      metabolic change contributed cell survival under stresses such as hypoxia and
      chemo-reagent, only when sufficient glucose supply was available. Augmented cell
      survival was based on the reduced ROS activity derived from metabolic alteration
      such as shift from oxidative phosphorylation to glycolysis and increased
      intracellular anti-oxidant, glutathione (GSH). One of the cystine transporters,
      rBAT is likely to play a major role in this GSH increase. These data suggest that
      HNF1beta, possibly induced by stressful microenvironment in the endometriotic
      cyst, confers survival advantage to the epithelial cells, which leads to the
      occurrence of OCCC, a chemo-resistant phenotype of ovarian cancer. 

PMID- 26318293
TI  - LAG3 and PD1 co-inhibitory molecules collaborate to limit CD8+ T cell signaling
      and dampen antitumor immunity in a murine ovarian cancer model.
AB  - The immune co-inhibitory receptors lymphocyte activation gene-3 (LAG3) and
      programmed cell death 1 (PD1) synergistically contribute to autoimmunity and
      tumor evasion. Here we demonstrate how they collaborate and interact to regulate
      T cell function. We first show that LAG3 and PD1 are co-expressed on both OVA
      specific and non-specific T cells infiltrating murine ovarian tumors. Dual
      antibody blockade or genetic knockout of LAG3 and PD1 significantly enhanced T
      effector function and delayed tumor growth. LAG3 and PD1 co-localized in
      activated CD8+ T cells in vitro at the trans-Golgi vesicles, early/recycling
      endosomal compartments, lysosomes, and microtubule organizing center.
      Importantly, LAG3 and PD1 cluster with pLck at the immunological synapse.
      Reciprocal immunoprecipitation of T cell extracts revealed physical interaction
      between LAG3 and PD1. Mutational analyses indicate that the cytoplasmic domain of
      LAG3 is not absolutely required for its association with PD1, while the ITIM and
      ITSM of PD1 are necessary for its association with LAG3. Finally, LAG3 protein
      also associates with the Src-homology-2 domain-containing phosphatases (SHP1/2)
      which are known to be recruited by PD1 during T cell signaling. Our data indicate
      that the association of LAG3 with PD1 contributes to their rapid trafficking to
      the immunological synapse, leading to a synergistic inhibitory effect on T cell
      signaling. 

PMID- 26318295
TI  - Regulation of p53 expression and apoptosis by vault RNA2-1-5p in cervical cancer
      cells.
AB  - nc886 or VRNA2-1 has recently been identified as a noncoding RNA instead of a
      vault RNA or a pre-microRNA. Several studies have reported that pre-miR-886 plays
      a tumor-suppressive role in a wide range of cancer cells through its activity as
      a cellular protein kinase RNA-activated (PKR) ligand and repressor. However, by
      sequencing stem-PCR products, we found that a microRNA originating from this
      precursor, vault RNA2-1-5p (VTRNA2-1-5p), occurs in cervical cancer cells. The
      expression levels of the predicted targets of VTRNA2-1-5p are negatively
      correlated with VTRNA2-1-5p levels by quantitative reversion transcription PCR
      (qRT-PCR). Previous results have shown that VTRNA2-1-5p is overexpressed in human
      cervical squamous cell carcinomas (CSCCs) compared with adjacent healthy tissues.
      Inhibition of VTRNA2-1-5p increases Bax protein expression and apoptotic cell
      death in cervical cancer cells. Our findings suggest that VTRNA2-1-5p has
      oncogenic activity related to the progression of cervical cancer. Here, we report
      that VTRNA2-1-5p directly targeted p53 expression and functioned as an oncomir in
      cervical cancer. VTRNA2-1-5p inhibition decreased cervical cancer cell invasion,
      proliferation, and tumorigenicity while increasing apoptosis and p53 expression.
      Interestingly, VTRNA2-1-5p inhibition also increased cisplatin-induced apoptosis
      of HeLa and SiHa cells. In human clinical cervical cancer specimens, low p53
      expression and high VTRNA2-1-5p expression were positively associated.In
      addition, VTRNA2-1-5p was found to directly target the 5' and 3' untranslated
      regions (UTRs) of p53. We propose that VTRNA2-1-5p is a direct regulator of p53
      and suggest that it plays an essential role in the apoptosis and proliferation of
      cervical cancer cells. 

PMID- 26318294
TI  - By activating Fas/ceramide synthase 6/p38 kinase in lipid rafts, stichoposide D
      inhibits growth of leukemia xenografts.
AB  - Stichoposide D (STD) is a marine triterpene glycoside isolated from sea
      cucumbers. We examined the molecular mechanisms underlying the antitumor activity
      of STD in human leukemia cells. The role of Fas (CD95), ceramide synthase 6
      (CerS6) and p38 kinase during STD-induced apoptosis was examined in human
      leukemia cells. In addition, the antitumor effects of STD in K562 and HL-60
      leukemia xenograft models were investigated. We found that STD induces Fas
      translocation to lipid rafts, and thus mediates cell apoptosis. We also observed
      the activation of CerS6 and p38 kinase during STD-induced apoptosis. The use of
      methyl-beta-cyclodextrin and nystatin to disrupt lipid rafts prevents the
      clustering of Fas and the activation of CerS6 and p38 kinase, and also inhibits
      STD-induced apoptosis. Specific inhibition by Fas, CerS6, and p38 kinase siRNA
      transfection partially blocked STD-induced apoptosis. In addition, STD has
      antitumor activity through the activation of CerS6 and p38 kinase without
      displaying any toxicity in HL-60 and K562 xenograft models. We observed that the
      anti-tumor effect of STD is partially prevented in CerS6 shRNA-silenced xenograft
      models. We first report that Fas/CerS6/p38 kinase activation in lipid rafts by
      STD is involved in its anti-leukemic activity. We also established that STD is
      able to enhance the chemosensitivity of K562 cells to etoposide or Ara-C. These
      data suggest that STD may be used alone or in combination with other
      chemotherapeutic agents to treat leukemia. 

PMID- 26318296
TI  - Becoming less tolerant with age: sugar maple, shade, and ontogeny.
AB  - Although shade tolerance is often assumed to be a fixed trait, recent work
      suggests ontogenetic changes in the light requirements of tree species. We
      determined the influence of gas exchange, biomass distribution, and self-shading
      on ontogenetic variation in the instantaneous aboveground carbon balance of Acer
      saccharum. We quantified the aboveground biomass distributions of 18 juveniles
      varying in height and growing in low light in a temperate forest understory in
      Minnesota, USA. Gas exchange rates of leaf and stem tissues were measured, and
      the crown architecture of each individual was quantified. The YPLANT program was
      used to estimate the self-shaded fraction of each crown and to model net leaf
      level carbon gain. Leaf respiration and photosynthesis per gram of leaf tissue
      increased with plant size. In contrast, stem respiration rates per gram of stem
      tissue declined, reflecting a shift in the distribution of stem diameter sizes
      from smaller (with higher respiration) to larger diameter classes. However, these
      trends were outweighed by ontogenetic increases in self-shading (which reduces
      the net photosynthesis realized) and stem mass fraction (which increases the
      proportion of purely respiratory tissue) in terms of influence on net carbon
      exchange. As a result, net carbon gain per gram of aboveground plant tissue
      declined with increasing plant size, and the instantaneous aboveground light
      compensation point increased. When estimates of root respiration were included to
      model whole-plant carbon gain and light compensation points, relationships with
      plant size were even more pronounced. Our findings show how an interplay of gas
      exchange, self-shading, and biomass distribution shapes ontogenetic changes in
      shade tolerance. 

PMID- 26318297
TI  - Diseases of the Upper Respiratory Tract in Preschool and School Age Children in
      Ambulatory Ear Nose Throat Practice.
AB  - The most common diseases of the upper respiratory tract in children treated by
      ear-nose-throat (ENT) specialists in ambulatory practice are infections, such as
      colds, rhinitis, sinusitis and pharyngitis, very frequently accompanied and
      promoted by chronic nasal obstructions of various etiology. These diseases, when
      treated incorrectly or for too long, cause frequent school absenteeism and may
      also lead to hearing disorders linked with acute or suppurative otitis. They may
      also habitually perpetuate abnormal breathing and result in occlusal disorders.
      The aim of this study was to assess the incidence and type of upper respiratory
      tract diseases in children, depending on age and sex of patients and on the
      seasons. We also discussed the role of the ENT specialist in the diagnosis and
      treatment of certain diseases. In the study we analyzed the medical records of
      patients of preschool and school age treated in the ENT outpatient clinic over
      one calendar year. It was found that the largest group of patients comprised
      children of 3-7 years of age, and most children visited the outpatient clinic in
      the period March-May. The most common main disorder, according to ICD-10, was
      acute nasopharyngitis (J00) and vasomotor and allergic rhinitis (J30). Among the
      comorbid disorders H65 and H66 were the most frequent. No significant gender
      differences were noted in the frequency of particular types of disease.

PMID- 26318298
TI  - miR-335 directly, while miR-34a indirectly modulate survivin expression and
      regulate growth, apoptosis, and invasion of gastric cancer cells.
AB  - miR-335 and miR-34a are two microRNAs (miRNAs) usually downregulated in gastric
      cancer (GC). But, their exact regulative roles were not fully elucidated. In this
      study, we studied the association between miR-335 and/or miR-34a expression and
      overall survival of GC patients and explored the regulative role of miR-335 and 
      34a over survivin expression and GC cell growth and invasion. Fifty patients with
      GC were regularly followed up from 2011 to 2015. miRNA microarray was used to
      examine the expression trend of miRNAs in eight tumor tissue samples and adjacent
      normal tissue samples. The possible binding site between miR-335 and survivin
      messenger RNA (mRNA) was predicted using online database and verified using qRT
      PCR, Western blot, and dual luciferase assay. The regulative role of miR-335 and
      miR-34a over GC cell growth, apoptosis, and invasion was studied using Cell
      Counting Kit-8 (CCK-8) assay, flow cytometry, and transwell assay, respectively.
      Among the GC patients, low miR-335 or miR-34a expression is associated with
      higher clinical stage and lymph node metastasis. Patients with low miR-335 or miR
      34a had poor overall survival, while those with combined low miR-335 and miR-34a
      expression had even poorer overall survival. miR-335 can directly regulate
      survivin expression through binding to the 3'UTR, while miR-34a has indirect
      modulating effect. Both miR-335 and miR-34a could inhibit cell proliferation and
      invasion and enhance cell apoptosis. But, these effects are largely abrogated by
      overexpression of survivin without 3'UTR. Therefore, besides the targets
      identified in previous studies, miR-335 and miR-34a can also regulate GC cell
      growth, apoptosis, and invasion at least partly through survivin. 

PMID- 26318299
TI  - Synergistic efficacy of gamma-radiation together with gallium trichloride and/or
      doxorubicin against Ehrlich carcinoma in female mice.
AB  - Combining chemotherapy with radiotherapy represents a key oncology strategy for a
      more comprehensive attack toward cancers and improves treatment outcome for
      various solid tumor malignancies. The present study aims to evaluate the
      synergistic antitumor effect of gamma-radiation together with gallium trichloride
      (GaCl3) and/or doxorubicin (DOX) against solid Ehrlich carcinoma (EC) in female
      mice. GaCl3 (300 mg/kg body weight (b.w.)) was administered by gavages daily on
      the seventh day after tumor inoculation, while the cytotoxic drug DOX (4 mg/kg
      b.w.) was administered intraperitoneally once a week. Whole-body gamma-radiation
      was carried out at a dose 2 Gy once a week. Biochemical analysis showed that
      solid EC induced a significant increase in malondialdehyde (MDA) content with a
      significant decrease in the antioxidant state (glutathione peroxidase (GPx) and
      catalase (CAT) activities) and depleted serum iron concentration compared to
      normal control. Moreover, a significant increase was observed in calcium level
      and caspase-3 concentrations in both serum and tumor homogenate respectively
      associated with a significant alteration in heart, liver, and kidney functions,
      as compared to control. Treatment of EC-bearing mice with GaCl3and/or DOX
      combined with gamma-radiation exposure significantly reduced tumor volume and
      displayed a significant improvement in most studied markers which may indicate a
      synergistic effect of this combination against organ dysfunction and cellular
      injury. The histopathologically investigation showed that treatment of animals
      bearing EC with GaCl3and/or DOX with gamma-radiation exposure showed shrinkage in
      tumor lesions and wide zones of apoptotic cells with signs of regenerations. It
      was concluded that the combination of GaCl3and/or DOX with gamma-radiation
      exposure resulted in super-additive cytotoxic effects on treatment of cancer
      cells. 

PMID- 26318300
TI  - Neo-epitopes on crotonaldehyde modified DNA preferably recognize circulating
      autoantibodies in cancer patients.
AB  - DNA damage is one of the leading causes of various pathological conditions
      including carcinogenesis. Crotonaldehyde is a 4-carbon unsaturated bifunctional
      aldehyde which is found ubiquitously and produced both exogenously and
      endogenously. It reacts with deoxyguanosine and form adducts with DNA. These
      adducts were detected and found involved in tumor formation in rats treated with
      crotonaldehyde. In the present study, structural changes in DNA by crotonaldehyde
      were evaluated by Fourier transform infrared (FTIR) spectroscopy, differential
      scanning colorimetry (DSC), dynamic light scattering (DLS), high-performance
      liquid chromatography (HPLC), and atomic force microscopy (AFM). Enhanced binding
      was observed in cancer autoantibodies with the DNA modified by crotonaldehyde
      than the native counterpart. Immunological studies revealed enhanced binding of
      cancer autoantibodies with crotonaldehyde modified DNA, compared to the native
      form. Furthermore, lymphocyte DNA isolated from cancer patients demonstrated
      considerable recognition of anti-Cro-DNA IgG as compared to the DNA from healthy
      individuals. Therefore, we suggest that crotonaldehyde modified DNA presents
      unique epitopes, that may trigger autoantibody induction in cancer patients. 

PMID- 26318301
TI  - In situ dendritic cell vaccination for the treatment of glioma and literature
      review.
AB  - Glioma is one of the greatest threats to human health, and invasive growth of
      glioma is its major cause of death. Inhibiting or blocking angiogenesis can
      effectively inhibit tumor growth and metastasis or dramatically reduce the size
      of the original lesion. Therefore, anti-angiogenic therapy has currently become
      the most promising treatment strategy for glioma. Although dendritic cells (DCs)
      used in DC-based immunotherapy are loaded with tumor-associated antigens, the
      anti-tumor 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. This article reviews the existing evidence regarding in situ DC
      vaccination for the treatment of glioma and puts forward hypotheses regarding
      patient, tumor, and technical factors and warrant further investigation. 

PMID- 26318302
TI  - Effects of radiotherapy on nasopharyngeal carcinoma cell invasiveness.
AB  - Radiotherapy is widely used in the treatment of nasopharyngeal carcinoma (NPC),
      whereas its effects on the NPC growth, survival, and metastases have not been
      completely evaluated. Here, we compared the detected metastatic NPC tissues after
      radiotherapy (m-NPC) to the resected primary NPC tissues prior to radiotherapy (p
      NPC). We detected higher levels of Snail2 protein, but not mRNA in m-NPC,
      compared to p-NPC. In vitro, a modest irradiation on NPC cells resulted in
      significant cell death, but increased Snail2 protein, but mRNA levels in the
      surviving NPC cells. Bioinformatics analyses showed that miR-613, which was
      significantly decreased in NPC cells after irradiation, targeted the 3'-UTR of
      Snail2 mRNA to inhibit its translation. Moreover, miR-613 overexpression
      inhibited Snail2-mediated cell invasiveness, while miR-613 depletion increased
      Snail2-mediated cell invasiveness in NPC cells. Finally, we detected
      significantly lower levels of miR-613 in m-NPC, compared to p-NPC. Together our
      data suggest that although radiotherapy induced NPC cell death, it may increase
      Snail2-mediated NPC cell invasiveness through downregulating miR-613.

PMID- 26318303
TI  - Apoptotic effects of non-edible parts of Punica granatum on human multiple
      myeloma cells.
AB  - Multiple myeloma is of great concern since existing therapies are unable to cure
      this clinical condition. Alternative therapeutic approaches are mandatory, and
      the use of plant extracts is considered interesting. Punica granatum and its
      derived products were suggested as potential anticancer agents due to the
      presence of bioactive compounds. Thus, polypenolic-rich extracts of the non
      edible parts of P. granatum were investigated for their antiproliferative and
      apoptotic effects on U266 multiple myeloma cells. We demonstrated that there were
      dose-dependent decreases in the proliferation of U266 cells in response to P.
      granatum extracts. Also, exposure to the extracts triggered apoptosis with
      significant increases in loss of mitochondrial membrane potential in U266 cells
      exposed to the leaves and stem extracts, while the flower extract resulted in
      slight increases in loss of MMP. These results were confirmed by Annexin-V
      analysis. These results documented the cytotoxic and apoptotic effects of P.
      granatum extracts on human U266 multiple myeloma cells via disruption of
      mitochondrial membrane potential and increasing cell cycle arrest. The data
      suggest that the extracts can be envisaged in cancer chemoprevention and call for
      further exploration into the potential application of these plant parts. 

PMID- 26318304
TI  - Circulating levels of the miRNAs, miR-194, and miR-29b, as clinically useful
      biomarkers for colorectal cancer.
AB  - The microRNAs (miRNAs), miR-194 and miR-29b, have been shown to downregulate in
      colorectal cancer (CRC) and may identify and classify CRC patients as compared
      with those in control subjects. In the current study, we aimed to explore whether
      the serum levels of the miRNAs could be potential biomarkers for diagnosis and
      prognosis of CRC. A quantitative reverse-transcription polymerase chain reaction
      (qRT-PCR) assay was utilized to determine and compare serum levels of miR-194 and
      miR-29b in 55 patients with CRC and 55 control subjects. The correlations between
      levels of the miRNAs and clinicopathological stages of cancer were analyzed in
      patients. Receiver operating characteristic (ROC) curve and survival analyses
      were carried out, respectively, to determine diagnostic and prognostic values of
      the miRNAs. Serum levels of miR-194 and miR-29b were found to be significantly
      lower in CRC patients than those in control subjects (P < 0.0001). Moreover,
      serum levels of the miRNAs in patients were inversely correlated with the
      advanced TNM stages (P = 0.01). ROC curve and survival analyses revealed that
      reduced levels of the miRNAs could serve as diagnostic and prognostic biomarkers
      for patients with CRC (P = 0.0001). Serum levels of miR-194 and miR-29b may serve
      as potential biomarkers for diagnosis and prognosis of CRC. 

PMID- 26318305
TI  - Upregulation of miR-129-5p affects laryngeal cancer cell proliferation,
      invasiveness, and migration by affecting STAT3 expression.
AB  - microRNA-129-5p may have a relationship with laryngeal squamous cell carcinoma
      (LSCC), but the expression and function of miRNA-129-5p are not fully understood.
      This study was performed to investigate the expression and function of miRNA-129
      5p in LSCC and its effects on STAT3. HBE and Hep-2 cells were cultured and
      analyzed by western blotting and real-time PCR. miR-129-5p expression was
      detected by real-time PCR. Hep-2 cells were transfected with a miR-129-5p
      expression vector. Cell proliferation, invasion, migration, cell cycle, and
      apoptosis assays were used to determine the role of miRNA-129-5p in the growth,
      invasion, and migration of LSCC cells and to determine the importance of STAT3 in
      these effects. STAT3 mRNA expression in Hep-2 cells was significantly higher than
      that in HBE cells (P < 0.05). miR-129-5p expression detected by real-time PCR
      showed that it was expressed at a lower level in Hep-2 cells than in HBE cells (P
      < 0.05). Compared with the control cells, the transfected cells showed lower
      STAT3 mRNA expression. For up to 7 days in culture, the transfected cells showed
      lower proliferation than the control cells (P < 0.05). After 24 h in culture, the
      apoptosis rate in miR-129-5p-transfected cells was 3.48 +/- 0.38 %, while the
      rate in control cells was 0.92 +/- 0.09 % (P = 0.0028), but the statistical
      significance was lost after 72 h in culture (P = 0.3180). The invasion and
      migration of the cells were inhibited after 24 and 72 h in culture when the miR
      129-5p expression in Hep-2 cells was upregulated (P = 0.0037 and 0.00383,
      respectively), while there was no statistically significant difference at 48 h (P
      = 0.0712). STAT3 expression could be suppressed by the upregulation of miR-129-5p
      expression. Both the proliferation and migration of tumor cells were suppressed
      when the level of STAT3 expression was decreased. The apoptosis rate of tumor
      cells was also increased. Based on these data, we suggest that miR-129-5p may
      directly inhibit STAT3 expression and play an important role in the development
      of LSCC. 

PMID- 26318306
TI  - Antileishmanial activity of compounds produced by endophytic fungi derived from
      medicinal plant Vernonia polyanthes and their potential as source of bioactive
      substances.
AB  - The purpose of this work was to evaluate the antileishmanial activity of
      endophytic fungi isolated from leaves of Vernonia polyanthes plant and their
      prospective use in the discovery of bioactive compounds. Sixteen endophytes were
      isolated by using potato dextrose agar medium and submitted to cultivation in
      rice medium. The fungal cultures were extracted with ethanol and used as crude
      extracts for testing their antileishmanial activity. The most active ethanol
      extract was obtained from P2-F3 strain, which was identified as Cochliobolus
      sativus by ITS rRNA gene sequence data. Followed by a bioassay-guided
      fractionation, the cochlioquinone A, isocochlioquinone A and
      anhydrocochlioquinone A compounds were isolated from the crude extracts and
      demonstrated to inhibit the parasites. From the present work, it is possible to
      conclude that endophytic fungi derived from medicinal plant V. polyanthes may be
      considered promising source for the discovery of bioactive compounds. 

PMID- 26318307
TI  - Further exploration of the conformational space of alpha-synuclein fibrils: solid
      state NMR assignment of a high-pH polymorph.
AB  - Polymorphism is a common and important phenomenon for protein fibrils which has
      been linked to the appearance of strains in prion and other neurodegenerative
      diseases. Parkinson disease is a frequently occurring neurodegenerative
      pathology, tightly associated with the formation of Lewy bodies. These deposits
      mainly consist of alpha-synuclein in fibrillar, beta-sheet-rich form. alpha
      synuclein is known to form numerous different polymorphs, which show distinct
      structural features. Here, we describe the chemical shift assignments, and derive
      the secondary structure, of a polymorph that was fibrillized at higher-than
      physiological pH conditions. The fibrillar core contains residues 40-95, with
      both the C- and N-terminus not showing any ordered, rigid parts. The chemical
      shifts are similar to those recorded previously for an assigned polymorph that
      was fibrillized at neutral pH. 

PMID- 26318308
TI  - Overexpression of a phospholipase Dalpha gene from Ammopiptanthus nanus enhances
      salt tolerance of phospholipase Dalpha1-deficient Arabidopsis mutant.
AB  - MAIN CONCLUSION: A phospholipase Dalpha gene ( AnPLDalpha ) was cloned from
      xerophytic desert plant Ammopiptanthus nanus and its overexpression enhanced salt
      tolerance of a PLDalpha1 deficient Arabidopsis mutant. Phospholipase Dalpha
      (PLDalpha) hydrolyzes phosphatidylcholine to produce phosphatidic acid, and plays
      crucial role in plant tolerance to abiotic stress. In this study, a phospholipase
      Dalpha gene (AnPLDalpha) was cloned from xerophyte Ammopiptanthus nanus by the
      methods of homologous cloning and rapid amplification of cDNA ends, and evaluated
      for its function in stress tolerance. The full-length cDNA was 2832 bp long,
      containing an open reading frame of 2427 bp that encodes 808 amino acids. The
      putative protein was predicted to be localized to the cytoplasm and this was
      confirmed by transient expression of a fluorescent fusion protein. The endogenous
      expression of the AnPLDalpha gene was induced by high salt, dehydration, cold and
      abscisic acid. The heterologous expression of the AnPLDalpha gene improved salt
      tolerance of an Arabidopsis pldalpha1 knocked out mutant, and positively
      regulated the expression of the AtABI, AtNCED, AtRD29A, AtRD29B and AtADH genes.
      Therefore, the AnPLDalpha gene was concluded to be involved in response to
      abiotic stress. The AnPLDalpha gene is a hopeful candidate for transgenic
      application to improve stress tolerance of commercial crops.

PMID- 26318310
TI  - Tracking transience: a method for dynamic monitoring of biological events in
      Arabidopsis thaliana biosensors.
AB  - MAIN CONCLUSION: The activation and level of expression of an endogenous, stress
      responsive biosensor (bioreporter) can be visualized in real-time and non
      destructively using highly accessible equipment (fluorometer). Biosensor output
      can be linked to computer-controlled systems to enable feedback-based control of
      a greenhouse environment. Today's agriculture requires an ability to precisely
      and rapidly assess the physiological stress status of plants in order to optimize
      crop yield. Here we describe the implementation and utility of a detection system
      based on a simple fluorometer design for real-time, continuous, and non
      destructive monitoring of a genetically engineered biosensor plant. We report the
      responses to heat stress of Arabidopsis thaliana plants expressing a Yellow
      Fluorescent Protein bioreporter under the control of the DREB2A temperature
      sensing promoter. Use of this bioreporter provides the ability to identify
      transient and steady-state behavior of gene activation in response to stress, and
      serves as an interface for novel experimental protocols. Models identified
      through such experiments inform the development of computer-based feedback
      control systems for the greenhouse environment, based on in situ monitoring of
      mature plants. More broadly, the work here provides a basis for informing
      biologists and engineers about the kinetics of bioreporter constructs, and also
      about ways in which other fluorescent protein constructs could be integrated into
      automated control systems.

PMID- 26318309
TI  - The short-term response of Arabidopsis thaliana (C3) and Zea mays (C4)
      chloroplasts to red and far red light.
AB  - MAIN CONCLUSION: Light quality has various effects on photochemistry and protein
      phosphorylation in Zea mays and Arabidopsis thaliana thylakoids due to different
      degrees of light penetration across leaves and redox status in chloroplasts. The
      effect of the spectral quality of light (red, R and far red, FR) on the function
      of thylakoid proteins in Zea mays and Arabidopsis thaliana was investigated. It
      was concluded that red light stimulates PSII activity in A. thaliana thylakoids
      and in maize bundle sheath (BS) thylakoids, but not in mesophyll (M) thylakoids.
      The light quality did not change PSI activity in M thylakoids of maize. FR used
      after a white light period increased PSI activity significantly in maize BS and
      only slightly in A. thaliana thylakoids. As shown by blue native (BN)-PAGE
      followed by SDS-PAGE, proteins were differently phosphorylated in the thylakoids,
      indicating their different functions. FR light increased dephosphorylation of
      LHCII proteins in A. thaliana thylakoids, whereas in maize, dephosphorylation did
      not occur at all. The rate of phosphorylation was higher in maize BS than in M
      thylakoids. D1 protein phosphorylation increased in maize and decreased in A.
      thaliana upon irradiation with both R and growth light (white light, W). Light
      variations did not change the level of proteins in thylakoids. Our data strongly
      suggest that response to light quality is a species-dependent phenomenon. We
      concluded that the maize chloroplasts were differently stimulated, probably due
      to different degrees of light penetration across the leaf and thereby the redox
      status in the chloroplasts. These acclimation changes induced by light quality
      are important in the regulation of chloroplast membrane flexibility and thus its
      function.

PMID- 26318311
TI  - Cross-talk between macrophages, smooth muscle cells, and endothelial cells in
      response to cigarette smoke: the effects on MMP2 and 9.
AB  - We hypothesized that matrix metalloproteinase secretion in response to cigarette
      smoke is modulated by cross-talk between resident cells within the aorta, namely,
      aortic smooth muscles, endothelial cells, and infiltrating macrophages, and this
      may be crucial for in vivo formation/progression of abdominal aortic aneurysm
      (AAA). Cigarette smoke extract (CSE) was applied to rat aortic smooth muscle
      (RASMC), endothelial (RAEC) or RAW cells, and conditioned media (CSE-CM)
      collected. Fresh cells were treated with CSE-CM for 24 h and then maintained in
      serum-free medium (SFM) for 72 h to analyze MMP2 and MMP9 in media by zymography
      and the ratio (pS/pJ) of phospho-Stat3 (pStat3) and phospho-Jak2 (pJak2) inside
      the cells by Western blot. We observed that CSE-CM from RAW and RAEC increased
      MMP9 by 200 and 17 %, respectively, in RASMC and also increased pS/pJ ratio (305
      and 228 %, respectively) in RASMC. RAW cell-derived CSE-CM induced RAEC to
      produce moderate amounts of MMP2 (17 %), MMP9 (30 %), and a 137 % increase in
      pS/pJ. RAW cells receiving unstimulated CM from RASMC and RAEC produced
      significant amounts of MMP9 (128 and 155 %, respectively) and increased pS/pJ (45
      and 1283 %, respectively). CSE-CM from RASMC and RAEC induced significant
      production of MMP9 from RAW cells (237 and 162 %, respectively) and increase in
      pS/pJ ratios (1348 and 1494 %, respectively). This is the first in vitro study
      demonstrating cigarette smoke extract-mediated differential interactions between
      resident cells in the aorta leads to altered modulation of signaling molecules
      that may be vital for AAA formation under in vivo conditions.

PMID- 26318312
TI  - MAPK/ERK signaling pathway-induced hyper-O-GlcNAcylation enhances cancer
      malignancy.
AB  - Dysregulated MAPK/ERK signaling is implicated in one-third of human tumors and
      represents an attractive target for the development of anticancer drugs.
      Similarly, elevated protein O-GlcNAcylation and O-GlcNAc transferase (OGT) are
      detected in various cancers and serve as attractive novel cancer-specific
      therapeutic targets. However, the potential connection between them remains
      unexplored. Here, a positive correlation was found between the activated MAPK/ERK
      signaling and hyper-O-GlcNAcylation in various cancer types and inhibition of the
      MAPK/ERK signaling by 10 uM U0126 significantly decreased the expression of OGT
      and O-GlcNAcylation in H1299, BPH-1 and DU145 cells; then, the pathway analysis
      of the potential regulators of OGT obtained from the UCSC Genome Browser was
      done, and ten downstream targets of ERK pathway were uncovered; the following
      results showed that ELK1, one of the ten targets of ERK pathway, mediated ERK
      signaling-induced OGT upregulation; finally, the MTT assay and the soft agar
      assay showed that the inhibition of MAPK/ERK signaling reduced the promotion
      effect of hyper-O-GlcNAcylation on cancer cell proliferation and anchorage
      independent growth. Taken together, our data originally provided evidence for the
      regulatory mechanism of hyper-O-GlcNAcylation in tumors, which will be helpful
      for the development of anticancer drugs targeting to hyper-O-GlcNAcylation. This
      study also provided a new mechanism by which MAPK/ERK signaling-enhanced cancer
      malignancy. Altogether, the recently discovered oncogenic factor O-GlcNAc was
      linked to the classical MAPK/ERK signaling which is essential for the maintenance
      of malignant phenotype of cancers.

PMID- 26318313
TI  - A Designed Metalloenzyme Achieving the Catalytic Rate of a Native Enzyme.
AB  - Terminal oxidases catalyze four-electron reduction of oxygen to water, and the
      energy harvested is utilized to drive the synthesis of adenosine triphosphate.
      While much effort has been made to design a catalyst mimicking the function of
      terminal oxidases, most biomimetic catalysts have much lower activity than native
      oxidases. Herein we report a designed oxidase in myoglobin with an O2 reduction
      rate (52 s(-1)) comparable to that of a native cytochrome (cyt) cbb3 oxidase (50
      s(-1)) under identical conditions. We achieved this goal by engineering more
      favorable electrostatic interactions between a functional oxidase model designed
      in sperm whale myoglobin and its native redox partner, cyt b5, resulting in a 400
      fold electron transfer (ET) rate enhancement. Achieving high activity equivalent
      to that of native enzymes in a designed metalloenzyme offers deeper insight into
      the roles of tunable processes such as ET in oxidase activity and enzymatic
      function and may extend into applications such as more efficient oxygen reduction
      reaction catalysts for biofuel cells. 

PMID- 26318314
TI  - Non-invasive measurements of pulse pressure variation and stroke volume variation
      in anesthetized patients using the Nexfin blood pressure monitor.
AB  - Nexfin beat-to-beat arterial blood pressure monitoring enables continuous
      assessment of hemodynamic indices like cardiac index (CI), pulse pressure
      variation (PPV) and stroke volume variation (SVV) in the perioperative setting.
      In this study we investigated whether Nexfin adequately reflects alterations in
      these hemodynamic parameters during a provoked fluid shift in anesthetized and
      mechanically ventilated patients. The study included 54 patients undergoing non
      thoracic surgery with positive pressure mechanical ventilation. The provoked
      fluid shift comprised 15 degrees  Trendelenburg positioning, and fluid
      responsiveness was defined as a concomitant increase in stroke volume (SV) >10 %.
      Nexfin blood pressure measurements were performed during supine steady state,
      Trendelenburg and supine repositioning. Hemodynamic parameters included arterial
      blood pressure (MAP), CI, PPV and SVV. Trendelenburg positioning did not affect
      MAP or CI, but induced a decrease in PPV and SVV by 3.3 +/- 2.8 and 3.4 +/- 2.7
      %, respectively. PPV and SVV returned back to baseline values after repositioning
      of the patient to baseline. Bland-Altman analysis of SVV and PPV showed a bias of
      -0.3 +/- 3.0 % with limits of agreement ranging from -5.6 to 6.2 %. The SVV was
      more superior in predicting fluid responsiveness (AUC 0.728) than the PVV (AUC
      0.636), respectively. The median bias between PPV and SVV was different for
      patients younger [-1.5 % (-3 to 0)] or older [+2 % (0-4.75)] than 55 years (P <
      0.001), while there were no gender differences in the bias between PPV and SVV.
      The Nexfin monitor adequately reflects alterations in PPV and SVV during a
      provoked fluid shift, but the level of agreement between PPV and SVV was low. The
      SVV tended to be superior over PPV or Eadyn in predicting fluid responsiveness in
      our population. 

PMID- 26318315
TI  - Investigation of peripheral photoplethysmographic morphology changes induced
      during a hand-elevation study.
AB  - A hand-elevation study was carried out in the laboratory in order to alter
      peripheral blood flow with the aim of increasing understanding of factors
      affecting the morphology of peripheral photoplethysmographic signals.
      Photoplethysmographic (PPG) signals were recorded from twenty healthy volunteer
      subjects during a hand-elevation study in which the right hand was raised and
      lowered relative to heart level, while the left hand remained static. Red and
      infrared (IR) PPG signals were obtained from the right and left index fingers
      using a custom-made PPG processing system. PPG features were identified using a
      feature-detection algorithm based on the first derivative of the PPG signal. The
      systolic PPG amplitude, the reflection index, crest time, pulse width at half
      height, and delta T were calculated from 20 s IR PPG signals from three positions
      of the right hand with respect to heart level (-50, 0, +50 cm) in 19 volunteers.
      PPG features were found to change with hand elevation. On lowering the hand to 50
      cm below heart level, ac systolic PPG amplitudes from the finger decreased by
      68.32 %, while raising the arm increased the systolic amplitude by 69.99 %. These
      changes in amplitude were attributed to changes in hydrostatic pressure and the
      veno-arterial reflex. Other morphological variables, such as crest time, were
      found to be statistically significantly different across hand positions,
      indicating increased vascular resistance on arm elevation than on dependency. It
      was hypothesized that these morphological PPG changes were influenced by changes
      in downstream venous resistance, rather than arterial, or arteriolar, resistance.
      Changes in hand position relative to heart level can significantly affect the
      morphology of the peripheral ac PPG waveform. These alterations are due to a
      combination of physical effects and physiological responses to changes in hand
      position, which alter vascular resistance. Care should be taken when interpreting
      morphological data derived from PPG signals and methods should be standardized to
      take these effects into account. 

PMID- 26318316
TI  - Is there any association between primary hyperparathyroidism and ocular changes,
      such as central corneal thickness, retinal thickness, and intraocular pressure?
AB  - Ocular changes are commonly encountered in various endocrine disorders. However,
      only a few studies have reported ocular changes in patients with primary
      hyperparathyroidism (PHPT). Here, we examined the central corneal thickness
      (CCT), retinal thickness (RT), and intraocular pressure (IOP), and their
      relationships with serum intact parathyroid hormone (iPTH), calcium (Ca), and
      phosphorus (P) levels in patients with PHPT. Thirty-seven eyes of 37 PHPT
      patients were compared with 43 eyes of 43 age- and sex-matched normal subjects. A
      detailed ophthalmologic examination, including CCT, RT, and IOP, was performed.
      CCT and IOP in PHPT patients were significantly higher than controls (p = 0.024
      and p = 0.038, respectively). No statistically significant difference was
      detected in RT between the two groups (p = 0.730). iPTH levels were positively
      correlated with CCT and IOP (r = 0.304, p = 0.006 and r = 0.249, p = 0.026,
      respectively). No significant correlation was found between iPTH levels and RT (p
      > 0.05), and between serum Ca levels, and RT, CCT, and IOP (all, p > 0.05). While
      there was a negative correlation between serum P levels and CCT (r = -0.264, p =
      0.018), no correlation was observed between serum P levels, and RT and IOP (both,
      p > 0.05). Using multiple regression analyses, iPTH, serum Ca, and serum P levels
      were found to have no significant associations with CCT, IOP, and RT (all, p >
      0.05). There was no significant association between PHPT, and CCT, RT, and IOP.
      We postulate that the identification of ocular aspects of PHPT is significant,
      and further studies related to this condition are required.

PMID- 26318317
TI  - Tree bark as a biomonitor for the determination of polychlorinated biphenyls and
      polybrominated diphenyl ethers from Southern Jiangsu, China: levels,
      distribution, and possible sources.
AB  - Tree bark was used as the passive air sampler to evaluate polychlorinated
      biphenyl (PCB) and polybrominated diphenyl ether (PBDE) pollution and possible
      sources in Southern Jiangsu. The concentrations of PCBs and Sigma7PBDEs were in
      the range of 0.58-5.19 ng/g dry weight (dw; mean 1.79 ng/g dw) and 17.9-243 pg/g
      dw (mean 74.7 pg/g dw), respectively. Tri-PCBs were the major PCB homologs, and
      technical PCB product Ar1242 was identified as the main source. BDE209
      concentrations (4.29-456 ng/g dw) were relatively high, indicating that BDE209
      pollution was serious in this region. The deca-BDE commercial mixture was the
      predominant commercial PBDE product used in this region. A good correlation was
      found between tree bark and polyurethane foam (PUF) disks in Sigma6PCB
      monitoring, suggesting that both of them respond well to the gas-phase PCB
      monitoring.

PMID- 26318318
TI  - Geochemistry and magnetic measurements of suspended sediment in urban sewage
      water vis-a-vis quantification of heavy metal pollution in Ganga and Yamuna
      Rivers, India.
AB  - Sewage water is becoming a key source of heavy metal toxicity in large river
      systems worldwide and the two major Himalayan Rivers in India (Ganga and Yamuna)
      are severely affected. The high population density in the river banks combined
      with increased anthropogenic and industrial activities is contributing to the
      heavy metal pollution in these rivers. Geochemical data shows a significant
      increase in the concentration of all heavy metals (Pb, 48-86 ppm; Zn, 360-834
      ppm; V, 45-101 ppm; Ni, 20-143 ppm; Cr, 79-266 ppm; Co, 8.62-22.12 ppm and Mn,
      313-603 ppm) in sewage and mixed water (sewage and river water confluence site)
      samples due to increased effluent discharge from the catchment area. The SigmaREE
      content of sewage water (129 ppm) is lower than the average mixed water samples
      (142 ppm). However, all the samples show similar REE pattern. The mass magnetic
      susceptibility (Xlf) values of suspended sediments (28 to 1000 * 10(-8) m(3) kg(
      1)) indicate variable concentration of heavy metals. The Xlf values show faint
      positive correlation with their respective bulk heavy metal contents in a limited
      sample population. The present study comprising geochemical analysis and first
      magnetic measurement data of suspended sediments in water samples shows a
      strongly polluted nature of Ganga and Yamuna Rivers at Allahabad contrary to the
      previous report mainly caused by overtly polluted city sewage water.

PMID- 26318319
TI  - Source identification and metallic profiles of size-segregated particulate
      matters at various sites in Delhi.
AB  - A study of elemental composition in the ambient air of Delhi was carried out in
      the monsoon, winter and summer seasons at four different sites from August 2012
      to April 2013 in the size ranges <1, 1-2.5, 2.5-10 and >10 MUm using "Dekati
      PM10" impactor. At each site, three samples were collected and were analyzed by
      energy-dispersive X-ray fluorescence (EDXRF). The presence of elements was found
      to be very common and highly concentrated in aerosol particles at all the sites,
      which are Na, Al, Si, K, Ca, Zn and Ba. Total suspended particulate matters
      (TSPMs) of fine particles were found high in comparison to coarse particles at
      all seasons. The TSPM of fine particles was found to be varied in the range from
      303.6 to 416.2 MUg/m(3). Similarly, the range of coarse TSPM was observed from
      162.9 to 262.8 MUg/m(3). Correlation matrices were observed between fine (size
      ranges <1 and 1-2.5 MUm) and coarse (size ranges 2.5-10 and >10 MUm) size
      particles for all elements with seasons. Source apportionments of elements were
      carried out using MS Excel 2010 through XLSTAT software. The source
      apportionments between fine and coarse particles were carried out through factor
      analysis and dominated sources found to be crustal re-suspension and industrial
      activities.

PMID- 26318320
TI  - Monitoring trees outside forests: a review.
AB  - Trees outside forests (TOFs) are an important natural resource that contributes
      substantially to national biomass and carbon stocks and to the livelihood of
      people in many regions. Over the last decades, decision makers have become
      increasingly aware of the importance of TOF, and as a consequence, this tree
      resource is nowadays often considered in forest monitoring systems. Our review
      shows that in many cases, TOF are included in national forest inventories,
      applying traditional methodologies with relatively sparse networks of field
      sample plots. Only in some countries, such as India, the design of the
      inventories has considered the special features of how TOFs occur in the
      landscape. Several research studies utilising remote sensing for monitoring TOF
      have been conducted lately, but very few studies include comparative studies to
      optimise sampling strategies for TOF. Our review indicates that methods combining
      remote sensing and field surveys appear to be very promising, especially when
      remote sensing techniques that assess both the horizontal and vertical structures
      of tree resources are applied. For example, two-phase sampling strategies with
      laser scanning in the first phase and a field survey in the second phase appear
      to be effective for assessing TOF resources. However, TOFs often exhibit
      different characteristics than forest trees. Thus, to improve TOF monitoring,
      there is often a need to develop models, e.g. for biomass assessment, that are
      specifically adapted to this tree resource. Alternatively, field-based remote
      sensing methods that provide structural information about individual trees,
      notably terrestrial laser scanning, could be further developed for TOF monitoring
      applications. This also would have a potential to reduce the problem of accessing
      TOF during field surveys, which is a problem, for example, in countries where TOF
      are present on intensively utilised private grounds like gardens and agricultural
      fields. 

PMID- 26318321
TI  - Synthesis and application of ion-imprinted polymer nanoparticles for the
      extraction and preconcentration of mercury in water and food samples employing
      cold vapor atomic absorption spectrometry.
AB  - We describe a nanosized Hg(II)-imprinted polymer that was prepared from
      methacrylic acid as functional monomer, ethyleneglycol dimethacrylate as cross
      linker, 2,2'-azobisisobutyronitrile (AIBN) as radical initiator, 2, 2'-di pyrydyl
      amine as a specific ligand, and Hg (II) as the template ions by precipitation
      polymerization method in methanol as the progeny solvent. Batch adsorption
      experiments were carried out as a function of pH, Hg (II) imprinted polymer
      amount, adsorption and desorption time, volume, and concentration of eluent. The
      synthesized polymer particles were characterized physically and morphologically
      by using infrared spectroscopy, thermogravimetric analysis, X-ray diffraction,
      and scanning electron microscopic techniques. The maximum adsorption capacity of
      the ion-imprinted and non-imprinted sorbent was 27.96 and 7.89 mg g(-1),
      respectively. Under optimal conditions, the detection limit for mercury was 0.01
      MUg L(-1) and the relative standard deviation was 3.2 % (n = 6) at the 1.00 MUg
      L(-1). The procedure was applied to determination of mercury in fish and water
      samples with satisfactory results.

PMID- 26318323
TI  - Erratum to: Comparison of the Diversity of Basidiomycetes from Dead Wood of the
      Manchurian fir (Abies holophylla) as Evaluated by Fruiting Body Collection,
      Mycelial Isolation, and 454 Sequencing.

PMID- 26318322
TI  - Efficacy and safety of percutaneous left atrial appendage closure to prevent
      thromboembolic events in atrial fibrillation patients with high stroke and
      bleeding risk.
AB  - AIMS: The randomized PROTECT AF trial demonstrated non-inferiority of left atrial
      appendage (LAA) closure to oral anticoagulation with warfarin. Current guidelines
      give a class IIb recommendation for LAA closure. We evaluated the efficacy and
      safety of LAA closure in a consecutive series of non-valvular atrial fibrillation
      patients with contraindications to long-term oral anticoagulation or at high
      bleeding risk. METHODS AND RESULTS: 101 consecutive non-valvular atrial
      fibrillation patients (age 74.7 +/- 7.5 years) at high risk for stroke (CHA2DS2
      VASc Score 4.4 +/- 1.6) and high bleeding risk (HAS-BLED Score 4.2 +/- 1.3)
      received LAA closure with either the Watchman closure device (n = 38) or the
      Amplatzer cardiac plug (n = 63). Dual antiplatelet therapy with aspirin and
      clopidogrel was recommended for 3-6 months after device implantation, followed by
      long-term antiplatelet therapy with aspirin. No anticoagulation was given after
      device implantation. Mean follow-up was 400 days. One patient (1 %) experienced a
      transient ischemic attack, and two patients (2 %) suffered from ischemic stroke.
      While on recommended antiplatelet therapy, bleeding occurred in 12/101 patients
      (12 %). Bleeding was significantly reduced with 3 compared with 6 months dual
      antiplatelet therapy (3.0 vs. 16.2 %, p < 0.05) while ischemic or thrombotic
      events were similar. CONCLUSION: Left atrial appendage closure in patients with
      non-valvular atrial fibrillation and high risk for stroke and bleeding events
      effectively prevented stroke and reduced cerebral ischemic events compared to
      expected stroke rate according to CHA2DS2-VASc Score. Dual antiplatelet therapy
      for 3 months reduced the rate of bleeding events compared to 6 months therapy
      with no increase of thrombotic events.

PMID- 26318325
TI  - Taste detection of the non-volatile isothiocyanate moringin results in deterrence
      to glucosinolate-adapted insect larvae.
AB  - Isothiocyanates (ITCs), released from Brassicales plants after hydrolysis of
      glucosinolates, are known for their negative effects on herbivores but mechanisms
      have been elusive. The ITCs are initially present in dissolved form at the site
      of herbivore feeding, but volatile ITCs may subsequently enter the gas phase and
      all ITCs may react with matrix components. Deterrence to herbivores resulting
      from topically applied volatile ITCs in artificial feeding assays may hence lead
      to ambiguous conclusions. In the present study, the non-volatile ITC moringin (4
      (alpha-L-rhamnopyranosyloxy)benzyl ITC) and its glucosinolate precursor
      glucomoringin were examined for effects on behaviour and taste physiology of
      specialist insect herbivores of Brassicales. In feeding bioassays, glucomoringin
      was not deterrent to larvae of Pieris napi (Lepidoptera: Pieridae) and Athalia
      rosae (Hymenoptera: Tenthredinidae), which are adapted to glucosinolates.
      Glucomoringin stimulated feeding of larvae of the related Pieris brassicae
      (Lepidoptera: Pieridae) and also elicited electrophysiological activity from a
      glucosinolate-sensitive gustatory neuron in the lateral maxillary taste sensilla.
      In contrast, the ITC moringin was deterrent to P. napi and P. brassicae at high
      levels and to A. rosae at both high and low levels when topically applied to
      cabbage leaf discs (either 12, 120 or 1200 nmol moringin per leaf disc of 1cm
      diameter). Survival of A. rosae was also significantly reduced when larvae were
      kept on leaves treated with moringin for several days. Furthermore, moringin
      elicited electrophysiological activity in a deterrent-sensitive neuron in the
      medial maxillary taste sensillum of P. brassicae, providing a sensory mechanism
      for the deterrence and the first known ITC taste response of an insect. In
      simulated feeding assays, recovery of moringin was high, in accordance with its
      non-volatile nature. Our results demonstrate taste-mediated deterrence of a non
      volatile, natural ITC to glucosinolate-adapted insects.

PMID- 26318324
TI  - Spatio-temporal Variation of Sediment Methanotrophic Microorganisms in a Large
      Eutrophic Lake.
AB  - Aerobic methane-oxidizing bacteria (MOB) play a crucial role in mitigating the
      methane emission from lake ecosystems to the atmosphere. However, the
      distribution of methanotrophic community in shallow and eutrophic lake and its
      influential factors remain essentially unclear. The present study investigated
      sediment methanotrophic microorganisms at different sites in eutrophic freshwater
      Dianchi Lake (China) in two different seasons. The abundance, diversity, and
      structure of sediment methanotrophic community showed a profound spatial and
      seasonal variation. The pmoA gene copy number in lake sediments ranged from 8.71
      +/- 0.49 * 10(4) to 2.09 +/- 0.03 * 10(7) copies per gram of dry sediment.
      Sediment methanotrophic communities were composed of Methylococcus and
      Methylobacter (type I methanotrophs) and Methylosinus (type II methanotrophs),
      while type I MOB usually outnumbered type II MOB. Moreover, ammonia nitrogen was
      found to be a potential determinant of methanotrophic community structure in
      Dianchi Lake. 

PMID- 26318326
TI  - Expanding the nasturlexin family: Nasturlexins C and D and their sulfoxides are
      phytoalexins of the crucifers Barbarea vulgaris and B. verna.
AB  - The metabolites produced in leaves of the crucifers winter cress (Barbarea
      vulgaris) and upland cress (Barbarea verna) abiotically elicited were
      investigated and their chemical structures were elucidated by analyses of
      spectroscopic data and confirmed by syntheses. Nasturlexins C and D and their
      sulfoxides are cruciferous phytoalexins displaying antifungal activity against
      the crucifer pathogens Alternaria brassicicola, Leptosphaeria maculans and
      Sclerotinia sclerotiorum. The biosynthesis of these metabolites is proposed based
      on pathways of cruciferous indolyl phytoalexins. This work indicates that B.
      vulgaris and B. verna have great potential as sources of defense pathways
      transferable to agriculturally important crops within the Brassica species. 

PMID- 26318327
TI  - Metabolite profiling and expression analysis of flavonoid, vitamin C and
      tocopherol biosynthesis genes in the antioxidant-rich sea buckthorn (Hippophae
      rhamnoides L.).
AB  - In this study, phenolic compounds were analyzed in developing berries of four
      Canadian grown sea buckthorn (Hippophae rhamnoides L.) cultivars ('RC-4',
      'E6590', 'Chuyskaya' and 'Golden Rain') and in leaves of two of these cultivars.
      Among phenolic acids, p-coumaric acid was the highest in berries, while gallic
      acid was predominant in leaves. In the flavonoid class of compounds,
      myricetin/rutin, kaempferol, quercetin and isorhamnetin were detected in berries
      and leaves. Berries of the 'RC-4' cultivar had approximately ? 2-fold higher
      levels of myricetin and quercetin at 17.5mg and 17.2 mg/100 g FW, respectively,
      than the other cultivars. The flavonoid content in leaves was considerably more
      than in berries with rutin and quercetin levels up to 135 mg and 105 mg/100 g FW,
      respectively. Orthologs of 15 flavonoid biosynthesis pathway genes were
      identified within the transcriptome of sea buckthorn mature seeds. Semi
      quantitative RT-PCR analysis of these genes in developing berries indicated
      relatively higher expression of genes such as CHS, F3'H, DFR and LDOX in the 'RC
      4' cultivar than in the 'Chuyskaya' cultivar. Vitamin C levels in ripened berries
      of the Canadian cultivars were on the high end of the concentration range
      reported for most other sea buckthorn cultivars. Orthologs of genes involved in
      vitamins C and E biosynthesis were also identified, expanding the genomic
      resources for this nutritionally important plant.

PMID- 26318328
TI  - Evaluation of patients diagnosed with essential arterial hypertension through
      network analysis.
AB  - BACKGROUND: Essential hypertension is a chronic pathology that causes long-term
      complications due to late diagnosis of patients, the inability to control the
      disease through medication, or due to the complexity of associated risk factors.
      AIMS: Our study sets out to identify specific patterns of response to arterial
      hypertension treatment, by taking into consideration the multiple connections
      between risk factors in a relevant population of hypertensive patients. METHODS:
      Network science is an emerging paradigm, branching over multiple aspects of
      physical, biological and social phenomena. One such branch, which has brought
      significant contributions to medical science, is the field of network medicine.
      To apply this methodology, we create a complex network of hypertensive patients
      based on their common medical conditions. Consequently, we obtain a community
      based representation which pinpoints specific-and previously uncharted-patterns
      of hypertension development. This approach creates incentives for evaluating
      patient's treatment efficacy, by considering its network topological position.
      RESULTS: Distinct clusters of patients with common properties have emerged for
      each study group (group A-treated with nebivolol, group B-treated with
      perindopril and group C-treated with candesartan cilexetil). Therefore, our
      network-based clustering allows for a better treatment assessment.

PMID- 26318329
TI  - Exploring mutualistic interactions between microalgae and bacteria in the omics
      age.
AB  - Microalgae undertake a wide range of mutualistic interactions with bacteria. Here
      we consider how transcriptomic, metagenomic and metabolomic approaches have been
      combined with microbiological and biochemical analyses to expand our
      understanding of algal-bacterial interactions. Identification of the major
      bacterial species associated with algae indicates that specific bacterial groups,
      particularly the alpha-Proteobacteria, are found more frequently, suggesting that
      these may have the means to initiate and maintain symbiotic relationships.
      Nutrient exchange is frequently the basis of algal-bacterial mutualism, and as
      the compounds involved are characterised, evidence is accumulating that these are
      complex and specific molecules, offering opportunities for signalling processes
      and regulation rather than merely passive diffusion. At the same time, it is
      clear that the interactions are not static, but can be initiated and broken in
      response to environmental and developmental cues. 

PMID- 26318331
TI  - Neuregulin 1 protects against ischemic brain injury via ErbB4 receptors by
      increasing GABAergic transmission.
AB  - Identifying novel neuroprotectants that can halt or even reverse the effects of
      stroke is of interest to both clinicians and scientists. Neuregulin 1 (NRG1) is
      an effective neuroprotectant, but its molecular mechanisms are largely unclear.
      In this study, NRG1 rescued cortical neurons from oxygen-glucose deprivation
      (OGD) model, but the effect was blocked by neutralizing NRG1 and ErbB4
      inhibition. In addition, gamma-Aminobutyric acid (GABA) receptor agonists had no
      synergistic effect with NRG1, and the neuroprotective effect of NRG1 against OGD
      was partly blocked by GABA receptor antagonists. Importantly, NRG1
      neuroprotection against brain ischemia was abolished in the mice with specific
      deletion of ErbB4 in parvalbumin (PV)-positive interneurons. In summary, NRG1
      protects against ischemic brain injury via ErbB4 receptors by enhancing GABAergic
      transmission. 

PMID- 26318330
TI  - Dynamic changes in extracellular release of GABA and glutamate in the lateral
      septum during social play behavior in juvenile rats: Implications for sex
      specific regulation of social play behavior.
AB  - Social play is a motivated and rewarding behavior that is displayed by nearly all
      mammals and peaks in the juvenile period. Moreover, social play is essential for
      the development of social skills and is impaired in social disorders like autism.
      We recently showed that the lateral septum (LS) is involved in the regulation of
      social play behavior in juvenile male and female rats. The LS is largely
      modulated by GABA and glutamate neurotransmission, but their role in social play
      behavior is unknown. Here, we determined whether social play behavior is
      associated with changes in the extracellular release of GABA and glutamate in the
      LS and to what extent such changes modulate social play behavior in male and
      female juvenile rats. Using intracerebral microdialysis in freely behaving rats,
      we found no sex difference in extracellular GABA concentrations, but
      extracellular glutamate concentrations are higher in males than in females under
      baseline conditions and during social play. This resulted in a higher
      glutamate/GABA concentration ratio in males vs. females and thus, an excitatory
      predominance in the LS of males. Furthermore, social play behavior in both sexes
      is associated with significant increases in extracellular release of GABA and
      glutamate in the LS. Pharmacological blockade of GABA-A receptors in the LS with
      bicuculline (100 ng/0.5 MUl, 250 ng/0.5 MUl) dose-dependently decreased the
      duration of social play behavior in both sexes. In contrast, pharmacological
      blockade of ionotropic glutamate receptors (NMDA and AMPA/kainate receptors) in
      the LS with AP-5+CNQX (2mM+0.4mM/0.5 MUl, 30 mM+3mM/0.5 MUl) dose-dependently
      decreased the duration of social play behavior in females, but did not alter
      social play behavior in males. Together, these data suggest a role for GABA
      neurotransmission in the LS in the regulation of juvenile social play behavior in
      both sexes, while glutamate neurotransmission in the LS is involved in the sex
      specific regulation of juvenile social play behavior.

PMID- 26318332
TI  - EphrinB-EphB signaling regulates spinal pain processing via PKCgamma.
AB  - Spinal ephrinB-EphB signaling is involved in the modulation of pain processing.
      The aim of the present study was to investigate whether protein kinase C-gamma
      (PKCgamma) acts as a downstream effector in regulating spinal pain processing
      associated with ephrinB-EphB signaling in mice. The intrathecal injection of
      ephrinB2-Fc, an EphB receptor activator, caused thermal hyperalgesia and
      mechanical allodynia, as well as increased activation of spinal PKCgamma.
      Knockdown of spinal PKCgamma prevented the pain behaviors induced by ephrinB2-Fc.
      Furthermore, the intrathecal injection of EphB2-Fc, an EphB receptor blocker,
      suppressed formalin-induced inflammatory, chronic constriction injury (CCI)
      induced neuropathic, and tibia bone cavity tumor cell implantation (TCI)-induced
      bone cancer pain behaviors, in addition to reducing the activation of spinal
      PKCgamma. Finally, the intrathecal injection of MK801, an N-methyl-D-aspartate
      (NMDA) receptor blocker, prevented the pain behaviors and spinal PKCgamma
      activation induced by ephrinB2-Fc. Overall, the results confirm the important
      role of PKCgamma in the regulation of spinal pain processing associated with
      ephrinB-EphB signaling.

PMID- 26318334
TI  - Prenatal toluene exposure impairs performance in the Morris Water Maze in
      adolescent rats.
AB  - Volatile organic solvent abuse continues to be a worldwide health problem,
      including the neurobehavioral teratogenic sequelae of toluene abuse during
      pregnancy. Although abuse levels of prenatal toluene exposure can lead to a Fetal
      Solvent Syndrome, there is little research examining these effects on memory.
      Consumption of toluene can have detrimental effects on the developing hippocampus
      which could lead to specific spatial learning and memory deficits. This study
      used a rat model to determine how prenatal exposure to abuse levels of toluene
      would affect performance in a spatial learning and memory task, the Morris Water
      Maze (MWM). Pregnant Sprague-Dawley rats were exposed to 0, 8000 or 12,000ppm
      (ppm) of toluene for 15min twice daily from gestation day 8 (GD8) through GD20.
      Male and female offspring (N=104) were observed in the MWM for 5days beginning on
      postnatal day (PN) 28 and again on PN44. While prenatal toluene-exposed animals
      did not differ in initial acquisition in the MWM, rats prenatally exposed to
      12,000ppm toluene displayed performance deficits during a probe trial and in
      reversal learning on PN44. Overall, this study indicates that prenatal exposure
      to repeated inhaled abuse patterns of high concentrations of toluene can impair
      spatial memory function that persists into adolescence.

PMID- 26318333
TI  - The Val66Met brain-derived neurotrophic factor gene variant interacts with early
      pain exposure to predict cortisol dysregulation in 7-year-old children born very
      preterm: Implications for cognition.
AB  - Early stress in the form of repetitive neonatal pain, in infants born very
      preterm, is associated with long-term dysregulation of the hypothalamic-pituitary
      adrenal (HPA) axis and with poorer cognitive performance. Brain-derived
      neurotrophic factor (BDNF) which is important in synaptic plasticity and
      cognitive functions is reduced by stress. Therefore the BDNF Val66Met variant,
      which affects secretion of BDNF, may interact with early exposure to pain-related
      stress in children born very preterm, to differentially affect HPA regulation
      that in turn may be associated with altered cognitive performance. The aims of
      this study were to investigate whether in children born very preterm, the BDNF
      Val66Met variant modulates the association between neonatal pain-related stress
      and cortisol levels at age 7years, and if cortisol levels were related to
      cognitive function. Furthermore, we examined whether these relationships were sex
      specific. Using a longitudinal cohort design, N=90 children born very preterm (24
      32weeks gestation) were followed from birth to age 7years. Cortisol was assayed
      from hair as an index of cumulative stress and from saliva to measure reactivity
      to a cognitive challenge. BDNF Val66Met variant was genotyped at 7years using
      real-time polymerase chain reaction (PCR). Using generalized linear modeling, in
      boys with the Met allele, greater neonatal pain-related stress (adjusted for
      clinical risk factors) predicted lower hair cortisol (p=0.006) and higher
      reactivity salivary cortisol (p=0.002). In both boys and girls with the Met
      allele, higher salivary cortisol reactivity was correlated with lower IQ (r=
      0.60; p=0.001) and poorer visual-motor integration (r=-0.48; p=0.008). Our
      findings show associations between lower BDNF availability (presence of the Met
      allele) and vulnerability to neonatal pain/stress in boys, but not girls. This
      exploratory study suggests new directions for research into possible mechanisms
      underlying how neonatal pain/stress is related to cognitive performance in
      children born very preterm.

PMID- 26318335
TI  - Transgenic labeling of parvalbumin-expressing neurons with tdTomato.
AB  - Parvalbumin (PVALB)-expressing fast-spiking interneurons subserve important roles
      in many brain regions by modulating circuit function and dysfunction of these
      neurons is strongly implicated in neuropsychiatric disorders including
      schizophrenia and autism. To facilitate the study of PVALB neuron function we
      need to be able to identify PVALB neurons in vivo. We have generated a bacterial
      artificial chromosome (BAC) transgenic mouse line expressing the red fluorophore
      tdTomato under the control of endogenous regulatory elements of the Pvalb gene
      locus (JAX # 027395). We show that the tdTomato transgene is faithfully expressed
      relative to endogenous PVALB expression throughout the brain. Furthermore,
      targeted patch clamp recordings confirm that the labeled populations in
      neocortex, striatum, and hippocampus are fast-spiking interneurons based on
      intrinsic properties. This new transgenic mouse line provides a useful tool to
      study PVALB neuron function in the normal brain as well as in mouse models of
      psychiatric disease. 

PMID- 26318336
TI  - Intrinsic dorsoventral patterning and extrinsic EGFR signaling genes control
      glial cell development in the Drosophila nervous system.
AB  - Dorsoventral patterning and epidermal growth factor receptor (EGFR) signaling
      genes are essential for determining neural identity and differentiation of the
      Drosophila nervous system. Their role in glial cell development in the Drosophila
      nervous system is not clearly established. Our study demonstrated that the
      dorsoventral patterning genes, vnd, ind, and msh, are intrinsically essential for
      the proper expression of a master glial cell regulator, gcm, and a
      differentiation gene, repo, in the lateral glia. In addition, we showed that esg
      is particularly required for their expression in the peripheral glia. These
      results indicate that the dorsoventral patterning and EGFR signaling genes are
      essential for identity determination and differentiation of the lateral glia by
      regulating proper expression of gcm and repo in the lateral glia from the early
      glial development. In contrast, overexpression of vnd, msh, spi, and Egfr genes
      repressed the expression of Repo in the ventral neuroectoderm, indicating that
      maintenance of correct columnar identity along the dorsoventral axis by proper
      expression of these genes is essential for restrictive formation of glial
      precursor cells in the lateral neuroectoderm. Therefore, the dorsoventral
      patterning and EGFR signaling genes play essential roles in correct identity
      determination and differentiation of lateral glia in the Drosophila nervous
      system. 

PMID- 26318337
TI  - Multiple stages of information processing are modulated during acute bouts of
      exercise.
AB  - Acute bouts of aerobic physical exercise can modulate subsequent cognitive task
      performance and oscillatory brain activity measured with electroencephalography
      (EEG). Here, we investigated the sequencing of these modulations of perceptual
      and cognitive processes using scalp recorded EEG acquired during exercise. Twelve
      participants viewed pseudo-random sequences of frequent non-target stimuli
      (cars), infrequent distractors (obliquely oriented faces) and infrequent targets
      that required a simple detection response (obliquely oriented faces, where the
      angle was different than the infrequent distractors). The sequences were
      presented while seated on a stationary bike under three conditions during which
      scalp recorded EEG was also acquired: rest, low-intensity exercise, and high
      intensity exercise. Behavioral target detection was faster during high-intensity
      exercise compared to both rest and low-intensity exercise. An event-related
      potential (ERP) analysis of the EEG data revealed that the mean amplitude of the
      visual P1 component evoked by frequent non-targets measured at parietal-occipital
      electrodes was larger during low-intensity exercise compared to rest. The P1
      component evoked by infrequent targets also peaked earlier during low-intensity
      exercise compared to rest and high-intensity exercise. The P3a ERP component
      evoked by infrequent distractors measured at parietal electrodes peaked
      significantly earlier during both low- and high-intensity exercise when compared
      to rest. The modulation of the visual P1 and the later P3a components is
      consistent with the conclusion that exercise modulates multiple stages of neural
      information processing, ranging from early stage sensory processing (P1) to post
      perceptual target categorization (P3a). 

PMID- 26318338
TI  - Is the glass half full or half empty? A qualitative exploration on treatment
      practices and perceived barriers to biomedical care for patients with nodding
      syndrome in post-conflict northern Uganda.
AB  - BACKGROUND: Nodding syndrome has increasingly become an issue of public health
      concern internationally. The etiology of the disorder is still unknown and there
      are yet no curative treatments. We explored perceptions about treatment practices
      and barriers to health seeking for nodding syndrome in Pader and Kitgum districts
      in northern Uganda in order to provide data necessary for informing policy on
      treatment adherence and rehabilitations. METHODS: We used focus group discussions
      and individual interviews to gain deep insights into help-seeking and treatment
      practices for nodding syndrome. Purposive sampling was used to identify
      information-rich participants that included village health teams, community
      members not directly affected with nodding syndrome, district leaders, healthcare
      professionals, and caregivers of children affected with nodding syndrome. We used
      qualitative content analysis to analyze data and presented findings under
      distinct categories and themes. RESULTS: Caregivers and communities sought care
      from multiple sources including biomedical facilities, traditional healers,
      traditional rituals from shrines, and spiritual healing. Nodding syndrome
      affected children reportedly have showed no enduring improvement with traditional
      medicines, traditional rituals, and prayers. A substantial minority of
      participants reported minimal improvements in symptoms of convulsions with use of
      western medicines. Challenges involved in health seeking included; (1) health
      system factors e.g. long distances to facilities, frequent unavailability of
      medicines, few healthcare providers, and long waiting times; (2) contextual and
      societal challenges e.g. lack of money for transport and medical bills,
      overburdening nature of the illness that does not allow time for other
      activities, and practical difficulties involved in transporting the physically
      deformed and mentally retarded children to the health facilities. CONCLUSIONS:
      Help-seeking for nodding syndrome is pluralistic and include use of traditional
      and biomedical practices. Western medicines admittedly showed at least short term
      control on nodding syndrome symptoms, especially convulsions and led in a few
      cases to regain of functional abilities. However, multiple barriers hinder health
      seeking and interfere with adherence to biomedical treatments. Regarding cure,
      there are hitherto no treatments participants perceive cure nodding syndrome.

PMID- 26318339
TI  - Generation of whole genome sequences of new Cryptosporidium hominis and
      Cryptosporidium parvum isolates directly from stool samples.
AB  - BACKGROUND: Whole genome sequencing (WGS) of Cryptosporidium spp. has previously
      relied on propagation of the parasite in animals to generate enough oocysts from
      which to extract DNA of sufficient quantity and purity for analysis. We have
      developed and validated a method for preparation of genomic Cryptosporidium DNA
      suitable for WGS directly from human stool samples and used it to generate 10
      high-quality whole Cryptosporidium genome assemblies. Our method uses a
      combination of salt flotation, immunomagnetic separation (IMS), and surface
      sterilisation of oocysts prior to DNA extraction, with subsequent use of the
      transposome-based Nextera XT kit to generate libraries for sequencing on Illumina
      platforms. IMS was found to be superior to caesium chloride density
      centrifugation for purification of oocysts from small volume stool samples and
      for reducing levels of contaminant DNA. RESULTS: The IMS-based method was used
      initially to sequence whole genomes of Cryptosporidium hominis gp60 subtype
      IbA10G2 and Cryptosporidium parvum gp60 subtype IIaA19G1R2 from small amounts of
      stool left over from diagnostic testing of clinical cases of cryptosporidiosis.
      The C. parvum isolate was sequenced to a mean depth of 51.8X with reads covering
      100 % of the bases of the C. parvum Iowa II reference genome (Bioproject PRJNA
      15586), while the C. hominis isolate was sequenced to a mean depth of 34.7X with
      reads covering 98 % of the bases of the C. hominis TU502 v1 reference genome
      (Bioproject PRJNA 15585). The method was then applied to a further 17 stools,
      successfully generating another eight new whole genome sequences, of which two
      were C. hominis (gp60 subtypes IbA10G2 and IaA14R3) and six C. parvum (gp60
      subtypes IIaA15G2R1 from three samples, and one each of IIaA17G1R1, IIaA18G2R1,
      and IIdA22G1), demonstrating the utility of this method to sequence
      Cryptosporidium genomes directly from clinical samples. This development is
      especially important as it reduces the requirement to propagate Cryptosporidium
      oocysts in animal models prior to genome sequencing. CONCLUSION: This represents
      the first report of high-quality whole genome sequencing of Cryptosporidium
      isolates prepared directly from human stool samples.

PMID- 26318340
TI  - Study of the protective effect on intestinal mucosa of the hydrosoluble fiber
      Plantago ovata husk.
AB  - BACKGROUND: Several studies have indicated that dietary fiber may have a
      protective effect on gastrointestinal mucosa. The aim of this study was to
      evaluate the protective action of the soluble fiber Plantago ovata husk against
      intestinal damage. METHODS: To evaluate the anti-ulcerogenic effect on duodenal
      mucosa of the soluble fiber Plantago ovata husk, low-dose acetylsalicylic acid
      (10 mg/kg) was given orally to animals once daily for 14 or 28 days with and
      without Plantago ovata husk (100 mg/kg). 24 h after final dosing duodenal samples
      were removed for anatomopathological evaluation. Villi were examined by both
      light and scanning electron microscopy. RESULTS: Acetylsalicylic acid induced
      severe lesions in duodenal mucosa of rabbits, including erosions, epithelium
      disorganization, and cell vacuolization, increasing as well the amount of
      mononuclear and caliciform cells. Damage was much more severe in animals treated
      for 28 days. In groups receiving Plantago ovata husk, a significant attenuation
      of acetylsalicylic acid-induced lesions was already observed in group treated for
      14 days, becoming more evident in those treated for 28 days, all of them with
      duodenal cytoarchitecture normal and similar to control animals. CONCLUSIONS:
      These findings suggest that Plantago ovata husk may protect intestinal mucosa
      probably by limiting acetylsalicylic acid penetration into epithelial cells,
      although further studies are needed to confirm the same effect in other
      experimental models of induced mucosal damage and to elucidate the mechanisms of
      fiber protection.

PMID- 26318341
TI  - Rhinoviral stimuli, epithelial factors and ATP signalling contribute to bronchial
      smooth muscle production of IL-33.
AB  - BACKGROUND: Bronchial smooth muscle cells (BSMCs) from severe asthmatics have
      been shown to overexpress the Th2-driving and asthma-associated cytokine IL-33.
      However, little is known regarding factors involved in BSMC production of IL-33.
      Rhinovirus (RV) infections cause asthma exacerbations, which exhibit features of
      Th2-type inflammation. Here, we investigated the effects of epithelial-derived
      media and viral stimuli on IL-33 expression in human BSMCs. METHODS: Primary
      human BSMCs from healthy (n = 3) and asthmatic (n = 3) subjects were stimulated
      with conditioned media from primary human bronchial epithelial cells (BECs),
      double-stranded (ds)RNA, dsRNA/LyoVec, or infected with RV. BSMCs were also
      pretreated with the purinergic receptor antagonist suramin. IL-33 expression was
      analysed by RT-qPCR and western blot and ATP levels were determined in cell
      supernatants. RESULTS: RV infection and activation of TLR3 by dsRNA increased IL
      33 mRNA and protein in healthy and asthmatic BSMCs. These effects were inhibited
      by dexamethasone. BSMC expression of IL-33 was also increased by stimulation of
      RIG-I-like receptors using dsRNA/LyoVec. Conditioned media from BECs induced BSMC
      expression of IL-33, which was further enhanced by dsRNA. BEC-derived medium and
      viral-stimulated BSMC supernatants exhibited elevated ATP levels. Blocking of
      purinergic signalling with suramin inhibited BSMC expression of IL-33 induced by
      dsRNA and BEC-derived medium. CONCLUSIONS: RV infection of BSMCs and activation
      of TLR3 and RIG-I-like receptors cause expression and production of IL-33.
      Epithelial-released factor(s) increase BSMC expression of IL-33 and exhibit
      positive interaction with dsRNA. Increased BSMC IL-33 associates with ATP release
      and is antagonised by suramin. We suggest that epithelial-derived factors
      contribute to baseline BSMC IL-33 production, which is further augmented by RV
      infection of BSMCs and stimulation of their pathogen-recognising receptors.

PMID- 26318342
TI  - Visual processing of optic flow and motor control in the human posterior
      cingulate sulcus.
AB  - Previous studies have shown that the human posterior cingulate contains a visual
      processing area selective for optic flow (CSv). However, other studies performed
      in both humans and monkeys have identified a somatotopic motor region at the same
      location (CMA). Taken together, these findings suggested the possibility that the
      posterior cingulate contains a single visuomotor integration region. To test this
      idea we used fMRI to identify both visual and motor areas of the posterior
      cingulate in the same brains and to test the activity of those regions during a
      visuomotor task. Results indicated that rather than a single visuomotor region
      the posterior cingulate contains adjacent but separate motor and visual regions.
      CSv lies in the fundus of the cingulate sulcus, while CMA lies in the dorsal bank
      of the sulcus, slightly superior in terms of stereotaxic coordinates. A
      surprising and novel finding was that activity in CSv was suppressed during the
      visuomotor task, despite the visual stimulus being identical to that used to
      localize the region. This may provide an important clue to the specific role
      played by this region in the utilization of optic flow to control self-motion. 

PMID- 26318343
TI  - Hypoxia induced epithelial-mesenchymal transition and vasculogenic mimicry
      formation by promoting Bcl-2/Twist1 cooperation.
AB  - Hypoxia plays a pivotal role in tumor progression. The functions of hypoxia and
      subsequent Bcl-2/Twist1 activation in epithelial-mesenchymal transition (EMT) and
      vasculogenic mimicry (VM) formation are currently unclear. This study aimed to
      investigate the role of Bcl-2/Twist1 cooperation in hypoxia-induced EMT and VM
      formation. In in vitro experiments, we found that hypoxia resulted in co
      overexpression of Bcl-2 and Twist1, facilitated Twist1 nuclear translocation and
      promoted EMT and VM formation. Co-overexpression of Bcl-2 and Twist1 under
      normoxia could also induce EMT and promote VM formation. Furthermore, blocking
      Bcl-2 or Twist1 attenuated the effects of hypoxia on EMT progress and VM
      formation in hepatocellular carcinoma cells. In in vivo experiments, the
      mechanism by which hypoxia promoted Bcl-2 and Twist1 co-overexpression and
      induced EMT process and VM formation was demonstrated using murine xenograft
      models. These results above suggest that hypoxia could activate the cooperation
      of Bcl-2 and Twist1, Bcl-2 plays an important role in assisting Twist1 nuclear
      translocation which could change the expression of a wide range of genes and lead
      to the induction of EMT and VM formation. 

PMID- 26318344
TI  - Recent Advances in the Selective Oxidation of Alkyl C-H Bonds Catalyzed by Iron
      Coordination Complexes.
AB  - Selective and stereoretentive oxidation of alkyl C-H bonds has been described
      over the last decade by employing biologically inspired iron coordination
      complexes as catalysts and hydrogen peroxide as oxidant. Examples of catalyst
      dependent C-H site selectivity have started to appear. The current paper
      describes an account of these findings. 

PMID- 26318345
TI  - [Perioperative pain therapy in orthopedics].
AB  - A sufficient pain management forms the foundation for a successful operative
      treatment of orthopedic patients. Clinical guideline standards must be provided
      to ensure safe and immediate pain therapy. Training in these guidelines should be
      held for clinical personnel on a regular basis. The visual analog scale (VAS) and
      the numerical rating scale (NRS) are valid instruments used for assessment of
      pain intensity. A sufficient pain management includes basic analgesics,
      analgesics on demand as well as special features, such as regional nerve blocks
      and patient-controlled anesthesia (PCA). The basic analgesics are primarily the
      groups of classical non-steroidal anti-inflammatory drugs (NSAID) and
      cyclooxygenase 2 (COX-2) inhibitors as well as stand by analgesics, such as
      metamizole. If there is further need for pain therapy, medium strong and strong
      opioids can be used but adverse events must be taken into consideration. 

PMID- 26318346
TI  - [Flexor tendon surgery].

PMID- 26318347
TI  - Left Ventricular Assist Devices: The Adolescence of a Disruptive Technology.
AB  - Clinical outcomes for patients with advanced heart failure receiving left
      ventricular assist devices are driven by appropriate patient selection, refined
      surgical technique, and coordinated medical care. Perhaps even more important is
      innovative pump design. The introduction and widespread adoption of continuous
      flow ventricular assist devices has led to a paradigm shift within the field of
      mechanical circulatory support, making the promise of lifetime device therapy
      closer to reality. The disruption caused by this new technology, on the one hand,
      produced meaningful improvements in patient survival and quality of life, but
      also introduced new clinical challenges, such as bleeding, pump thrombosis, and
      acquired valvular heart disease. Further evolution within this field will require
      financial investment to sustain innovation leading to a fully implantable,
      durable, and cost-effective pump for a larger segment of patients with advanced
      heart failure. 

PMID- 26318348
TI  - Declining an LVAD: New Thoughts About an Old Problem.

PMID- 26318349
TI  - Extensive community-acquired pneumonia with hemophagocytic syndrome caused by
      Aeromonas veronii in an immunocompetent patient.

PMID- 26318350
TI  - Seroepidemiology of pertussis among elementary school children in northern
      Taiwan.
AB  - BACKGROUND/PURPOSE: Pertussis has been considered a vaccine-preventable
      "childhood disease", but a shift in age distribution has been reported worldwide.
      We conducted a seroepidemiological study in 2013 in Taiwan to elucidate the
      seroprevalence of pertussis among elementary school children. METHODS: With a
      multilevel randomized method, which included 14 variables (4 population
      variables, 4 socio-educational variables, and 6 medical facilities' variables),
      the 29 executive districts of New Taipei City, Taiwan, were categorized into five
      strata. From each stratum, the number of school children as well as the number of
      elementary schools were proportionally selected. Enzyme immunoassay was applied
      for pertussis immunoglobulin-G measurement. RESULTS: A total of 936 children from
      14 schools were recruited. Most participants (98.89%) received at least three
      doses of acellular diphtheria-tetanus-pertussis vaccine. The overall seropositive
      rate for pertussis was 33.97%. The seropositive rate was highest for students in
      Grade 1 (49.36%) and then declined with time, except for Grade 6 students.
      Students from Grade 1 to Grade 4 had a significant higher seropositive rate
      (37.18% vs. 27.56%, p = 0.002) than those from Grade 5 to Grade 6, but a lower
      geometric mean titer (18.71 NovaTec Unit/mL vs. 20.04 NovaTec Unit/mL, p = 0.20).
      For the class grades, geometric mean titers were positively correlated with
      seroprevalence (p < 0.005). CONCLUSION: Currently, almost one-third of elementary
      school children in Taiwan were seropositive for pertussis, a rate lower than
      expected. Seroprevalence declined with increasing class grades except for Grade
      6. The current national immunization program may not provide adequate protection
      for children against pertussis.

PMID- 26318351
TI  - Minimalist transcatheter aortic valve replacement: The new standard for surgeons
      and cardiologists using transfemoral access?
AB  - BACKGROUND: A minimalist approach for transcatheter aortic valve replacement (MA
      TAVR) utilizing transfemoral access under conscious sedation and transthoracic
      echocardiography is increasing in popularity. This relatively novel technique may
      necessitate a learning period to achieve proficiency in performing a successful
      and safe procedure. This report evaluates our MA-TAVR cohort with specific
      characterization between our early, midterm, and recent experience. METHODS: We
      retrospectively reviewed 151 consecutive patients who underwent MA-TAVR with
      surgeons and interventionists equally as primary operator at Emory University
      between May 2012 and July 2014. Our institution had performed 300 TAVR procedures
      before implementation of MA-TAVR. Patient characteristics and early outcomes were
      compared using Valve Academic Research Consortium 2 definitions among 3 groups:
      group 1 included the first 50 patients, group 2 included patients 51 to 100, and
      group 3 included patients 101 to 151. RESULTS: Median age for all patients was 84
      years and similar among groups. The majority of patients were men (56%) and the
      median ejection fraction for all patients was 55% (interquartile range, 38.0%
      60.0%). The majority of patients were high-risk surgical candidates with a median
      Society of Thoracic Surgeons Predicted Risk of Mortality of 10.0% and similar
      among groups. The overall major stroke rate was 3.3%, major vascular
      complications occurred in 3% of patients, and greater-than-mild paravalvular leak
      rate was 7%. In-hospital mortality and morbidity were similar among all 3 groups.
      CONCLUSIONS: In a high-volume TAVR center, transition to MA-TAVR is feasible with
      acceptable outcomes and a diminutive procedural learning curve. We advocate for
      TAVR centers to actively pursue the minimalist technique with equal
      representation by cardiologists and surgeons.

PMID- 26318352
TI  - Stenting of ventricular septal defects to retrain the left ventricle in patients
      with transposition of the great arteries and restrictive ventricular septal
      defect.

PMID- 26318353
TI  - The emperor's new clothes.

PMID- 26318354
TI  - Main pulmonary artery area limits exercise capacity in patients long-term after
      arterial switch operation.
AB  - OBJECTIVES: Despite excellent survival in patients after the arterial switch
      operation, reintervention is frequently required and exercise capacity is
      decreased in a substantial number of patients. This study relates right-sided
      imaging features in patients long-term after the arterial switch operation to
      exercise capacity and ventilatory efficiency to investigate which lesions are
      functionally important. METHODS: Patients operated in the UMC Utrecht, the
      Netherlands (1976-2001) and healthy controls underwent cardiac magnetic resonance
      imaging and cardiopulmonary exercise testing within 1 week. We measured main,
      left, and right pulmonary artery cross-sectional areas, pulmonary blood flow
      distribution, peak oxygen uptake, and minute ventilation relative to carbon
      dioxide elimination. RESULTS: A total of 71 patients (median age, 20 [12-35]
      years, 73% were male) and 21 healthy controls (median age, 26 [21-35] years, 48%
      were male) were included. Main, left, and right pulmonary artery areas were
      decreased compared with controls (190 vs 269 mm(2)/m(2), 59 vs 157 mm(2)/m(2), 98
      vs 139 mm(2)/m(2), respectively, all P < .001); however, pulmonary blood flow
      distribution was comparable (P = .722). Peak oxygen uptake and minute ventilation
      relative to carbon dioxide elimination were 88% +/- 20% and 23.7 +/- 3.8,
      respectively, with 42% and 1% of patients demonstrating abnormal results (<= 84%
      and >= 34, respectively). The main pulmonary artery area significantly correlated
      with peak oxygen uptake (r = 0.401, P = .001) and pulmonary blood flow
      distribution with minute ventilation relative to carbon dioxide elimination (r = 
      0.329, P = .008). Subanalysis (<18, 18-25, >25 years) showed that the main
      pulmonary artery area was smaller in older age groups. In multivariable analysis,
      the main pulmonary artery area was independently associated with peak oxygen
      uptake (P = .032). CONCLUSIONS: In adult patients after the arterial switch
      operation, narrowing of the main pulmonary artery is a common finding and is the
      main determinant of limitation in functional capacity, rather than pulmonary
      branch stenosis.

PMID- 26318356
TI  - Discussion.

PMID- 26318355
TI  - A liberal strategy of red blood cell transfusion reduces cardiogenic shock in
      elderly patients undergoing cardiac surgery.
AB  - OBJECTIVE: The aim of this study was to compare outcomes in patients undergoing
      cardiac surgery who are aged 60 years or more or less than 60 years after
      implementation of a restrictive or a liberal transfusion strategy. METHODS: This
      is a substudy of the Transfusion Requirements After Cardiac Surgery (TRACS)
      randomized controlled trial. In this subgroup analysis, we separated patients
      into those aged 60 years or more (elderly) and those aged less than 60 years
      randomized to a restrictive or a liberal strategy of red blood cell transfusion.
      The primary outcome was a composite defined as a combination of 30-day all-cause
      mortality and severe morbidity. RESULTS: Of the 502 patients included in the
      Transfusion Requirements After Cardiac Surgery study, 260 (51.8%) were aged 60
      years or more and 242 (48.2%) were aged less than 60 years and were included in
      this study. The primary end point occurred in 11.9% of patients in the liberal
      strategy group and 16.8% of patients in the restrictive strategy group (P = .254)
      for those aged 60 years or more and in 6.8% of patients in the liberal strategy
      group and 5.6% of patients in the restrictive strategy group for those aged less
      than 60 years (P = .714). However, in the older patients, cardiogenic shock was
      more frequent in patients in the restrictive transfusion group (12.8% vs 5.2%, P
      = .031). Thirty-day mortality, acute respiratory distress syndrome, and acute
      renal injury were similar in the restrictive and liberal transfusion groups in
      both age groups. CONCLUSIONS: Although there was no difference between groups
      regarding the primary outcome, a restrictive transfusion strategy may result in
      an increased rate of cardiogenic shock in elderly patients undergoing cardiac
      surgery compared with a more liberal strategy. Cardiovascular risk of anemia may
      be more harmful than the risk of blood transfusion in older patients.

PMID- 26318357
TI  - Symptom assessment and exercise impairment in surgical decision making in
      hypertrophic obstructive cardiomyopathy: Relationship to outcomes.
AB  - OBJECTIVES: We sought to assess the long-term outcomes in patients with
      hypertrophic cardiomyopathy and severe left ventricular outflow tract
      obstruction, in whom the decision regarding surgery (vs conservative management)
      was based on assessment of symptoms or exercise capacity. METHODS: This was an
      observational study of 1530 patients with hypertrophic cardiomyopathy (aged 50 +/
      13 years, 63% were men) with severe left ventricular outflow tract obstruction
      (excluding those aged <18 years, with left ventricular ejection fraction <50%,
      and with left ventricular outflow tract gradient <30 mm Hg). A composite end
      point of death (excluding noncardiac causes) and/or implantable defibrillator
      discharge was assessed. RESULTS: Coronary artery disease, family history of
      hypertrophic cardiomyopathy, and syncope were present in 15%, 17%, and 18% of
      patients, respectively, whereas 73% patients were in New York Heart Association
      class II or greater. Mean left ventricular ejection fraction, basal septal
      thickness, and left ventricular outflow tract gradient (resting or provocable)
      were 62% +/- 5%, 2.2 +/- 1 cm, and 101 +/- 39 mm Hg, respectively. A total of 858
      patients (56%) underwent exercise echocardiography, of whom 503 (59%) had
      exercise capacity impairment. At 8.1 +/- 6 years, 990 patients (65%) underwent
      surgical relief of left ventricular outflow tract obstruction, and 540 patients
      (35%) did not. There were 156 events (10%) (134 deaths), with 0% 30-day mortality
      in the surgical group. On multivariable Cox proportional hazard analysis,
      increasing age (hazard ratio [HR], 1.20), coronary artery disease (HR, 1.68),
      worse New York Heart Association class (HR, 1.46), and atrial fibrillation (HR,
      1.90) predicted higher events, whereas surgery (time-dependent covariate HR,
      0.57) was associated with improved event-free survival (all P < .01).
      CONCLUSIONS: In patients with hypertrophic cardiomyopathy and severe left
      ventricular outflow tract obstruction, in whom the decision regarding surgery was
      based on the presence of intractable symptoms and impaired exercise capacity,
      surgery was associated with significant improvement in long-term composite
      outcomes.

PMID- 26318358
TI  - Preoperative predictors and outcomes of right ventricular assist device
      implantation after continuous-flow left ventricular assist device implantation.
AB  - OBJECTIVE: The outcomes of ventricular assist device therapy remain limited by
      right ventricular failure. We sought to define the predictors and evaluate the
      outcomes of right ventricular failure requiring right ventricular assist device
      support after long-term continuous-flow left ventricular assist device
      implantation. METHODS: Records of all continuous-flow left ventricular assist
      device recipients for the last 10 years were analyzed, including patients on
      preoperative intra-aortic balloon pump, extracorporeal membrane oxygenation, and
      short-term ventricular assist device support. Perioperative clinical,
      echocardiographic, hemodynamic, and laboratory data of continuous-flow left
      ventricular assist device recipients requiring right ventricular assist device
      support (right ventricular assist device group) were compared with the rest of
      the patient cohort (control group). RESULTS: Between July 2003 and June 2013, 152
      patients underwent continuous-flow left ventricular assist device implantation as
      a bridge to transplantation. The overall postoperative incidence of right
      ventricular assist device support was 23.02% (n = 35). Right ventricular assist
      device implantation did not significantly affect eventual transplantation (P =
      .784) or longer-term survival (P = .870). Preoperative right ventricular diameter
      (P < .001), tricuspid annular plane systolic excursion (P < .001), previous
      sternotomy (P = .002), preoperative short-term mechanical support (P = .005),
      left atrial diameter (P = .014), female gender (P = .020), age (P = .027), and
      preoperative bilirubin levels (P = .031) were univariate predictors of right
      ventricular assist device implantation. Multivariate analysis revealed lesser
      tricuspid annular plane systolic excursion (P = .013; odds ratio, 0.613; 95%
      confidence interval, 0.417-0.901) and smaller left atrial diameter (P = .007;
      odds ratio, 0.818; 95% confidence interval, 0.707-0.947) as independent
      predictors of right ventricular assist device implantation. Receiver operating
      characteristic curve of tricuspid annular plane systolic excursion yielded an
      area under the curve of 0.85 (95% confidence interval, 0.781-0.923), with cutoff
      tricuspid annular plane systolic excursion less than 12.5 mm having 84%
      sensitivity and 75% specificity. CONCLUSIONS: Lesser tricuspid annular plane
      systolic excursion and smaller left atrial diameter are independent predictors of
      the need for right ventricular assist device support after continuous-flow left
      ventricular assist device implantation. Right ventricular assist device
      implantation does not adversely affect eventual transplantation or survival after
      continuous-flow left ventricular assist device implantation.

PMID- 26318359
TI  - Mechanistic modeling of ophthalmic drug delivery to the anterior chamber by eye
      drops and contact lenses.
AB  - Ophthalmic drug for the anterior chamber diseases are delivered into tears by
      either eye drops or by extended release devices placed in the eyes. The instilled
      drug exits the eye through various routes including tear drainage into the nose
      through the canaliculi and transport across various ocular membranes.
      Understanding the mechanisms relevant to each route can be useful in predicting
      the dependency of ocular bioavailability on various formulation parameters, such
      as drug concentration, salinity, viscosity, etc. Mathematical modeling has been
      developed for each of the routes and validated by comparison with experiments.
      The individual models can be combined into a system model to predict the fraction
      of the instilled drug that reaches the target. This review summarizes the
      individual models for the transport of drugs across the cornea and conjunctiva
      and the canaliculi tear drainage. It also summarizes the combined tear dynamics
      model that can predict the ocular bioavailability of drugs instilled as eye
      drops. The predictions from the individual models and the combined model are in
      good agreement with experimental data. Both experiments and models predict that
      the corneal bioavailability for drugs delivered through eye drops is less than 5%
      due to the small area of the cornea in comparison to the conjunctiva, and the
      rapid clearance of the instilled solution by tear drainage. A contact lens is a
      natural choice for delivering drugs to the cornea due to the placement of the
      contact in the immediate vicinity of the cornea. The drug released by the contact
      towards the cornea surface is trapped in the post lens tear film for extended
      duration of at least 30min allowing transport of a large portion into the cornea.
      The model predictions backed by in vivo animal and clinical data show that the
      bioavailability increases to about 50% with contact lenses. This realization has
      encouraged considerable research towards delivering ocular drugs by contact
      lenses. Commercial contacts are, however, not ideal for drug delivery due to the
      short release durations which may necessitate wearing multiple lenses each day,
      reducing the viability of this approach. Recent research has focused on designing
      contacts that retain all critical properties while increasing the release
      durations to a few hours or a few days. Beagle dog studies with contact lenses
      containing vitamin E nanobarriers to attenuate drug transport have shown
      promising results. Human studies using contacts for drug delivery have also been
      conducted for allergy therapy but drug eluting contacts are not available in the
      market for any therapy. 

PMID- 26318360
TI  - Incidence, hospital costs and in-hospital mortality rates of epidural hematoma in
      the United States.
AB  - OBJECTIVE: This study provides the first United States (US) national data
      regarding frequency, cost and mortality rate of epidural hematoma (EDH) and
      determines the factors affecting the morbidity and deaths in the patients with
      EDH undergoing surgical evacuation. METHODS: A retrospective analysis was
      performed by searching the Nationwide Inpatient Sample (NIS) from 2003 to 2010,
      the largest all payer database of non-federal community hospitals in the US. All
      cases of EDH were indentified using ICD-9 codes. RESULTS: A total of 5189
      admissions were identified in the NIS database, and incidence was highest in the
      second decade (33.4%). The median length of stay in the hospital was about 4 days
      in each year (2003-2010) without significant difference. The percent of discharge
      disposition other than home was about 2-3% in the entire cohort, with the highest
      in 2009 (3%). The average cost per admission increased significantly (80%) from
      $45,850 in 2003 to $82,800 in 2010. The inhospital mortality and complication
      rate was 3.5% and 2.9%, respectively. Factors affecting in-hospital mortality
      rate were age (<=18 yr vs. >18 yr, P<0.001), insurance type (medicare vs. private
      insurance, P<0.001), co-morbidities (high vs. low, P<0.001), hospital volume
      (high vs. low volume, P<0.001), physician's case volumes (high vs. low volume,
      P<0.02), hospital type (teaching vs. non-teaching, P<0.01) and hospital region
      (South vs. others, P<0.02). Similarly, factors affecting adverse outcome at
      discharge were age (<=18 yr vs. >18 yr, P<0.001), female gender (P<0.001), median
      income (fourth quartile vs. other, P<0.001), ethnicity (African-American vs. non
      African-American, P<0.02), insurance type (medicare vs. private insurance,
      P<0.001), co-morbidities (high vs. low, P<0.001), hospital case volume (4th
      quartile volume vs. other, P<0.001), physician's case volume (4th quartile volume
      vs. other, P<0.0001), hospital type (teaching vs. non-teaching, hospital bed size
      (small vs. large, P<0.001), hospital region (Northeast vs. others, P<0.001) and
      hospital location (urban vs. rural, P<0.001). CONCLUSION: Nationally, there has
      been no significant change in the frequency of EDH. However, its cost is
      increasing rapidly.

PMID- 26318361
TI  - Hemodynamic stress distribution reflects ischemic clinical symptoms of patients
      with moyamoya disease.
AB  - OBJECTIVE: Currently, the probability of diagnosing asymptomatic moyamoya disease
      is increasing. In this study, we consider a less invasive method for predicting
      future ischemic symptoms in patients with moyamoya disease. METHODS: We reviewed
      cerebral blood flow (CBF)-related data obtained by xenon CT imaging (XeCT) in six
      patients with ischemic-type or asymptomatic moyamoya disease. The data were
      obtained as volume data using a 320-row CT, and applied to the automated region
      of-interest-determining software (3DSRT) and converted to standardized images.
      Eight CBF-related parameters, including CBF value, cerebrovascular reserve
      capacity (CVRC), and hemodynamic distribution (hdSD), were compared between
      asymptomatic hemispheres and ischemic symptomatic hemispheres. A significant
      difference was determined by a two-sample t test. A difference with p<0.05 was
      considered significant. When statistically significant differences between
      parameters of asymptomatic hemispheres and ischemic symptomatic hemispheres were
      identified, cut-off points were calculated with receiver operating characteristic
      (ROC) curves. Change in the parameters before and after bypass surgery was also
      assessed. RESULTS: Of the eight CBF-related parameters evaluated, statistically
      significant differences between the asymptomatic hemispheres and ischemic
      hemispheres were observed in the CBF value of the MCA region (CBF-MCA), both at
      rest and after acetazolamide loading, and in the hdSD, also both at rest and
      after acetazolamide loading. Of the four statistically significant parameters,
      ROC analysis revealed that the hdSD at rest and CBF-MCA after acetazolamide
      loading were the most sensitive and specific parameters (threshold 1.2,
      sensitivity 1, specificity 1 for hdSD at rest, and threshold 26.44mL/100g/min,
      sensitivity 1, specificity 1 for CBF-MCA after acetazolamide loading). From the
      CBF data obtained both before and after surgery from the three patients who had
      undergone direct bypass surgeries, the hdSD was higher than the threshold of 1.2
      before surgery but decreased to lower than the threshold of 1.2 after surgery.
      Ischemic symptoms also resolved after surgery. CONCLUSIONS: The data showed that
      hdSD at rest and CBF-MCA after acetazolamide loading reflects ischemic symptoms
      of patients with moyamoya disease. Thus, these parameters could be used as
      ischemic symptom markers for following patients with moyamoya disease. hdSD at
      rest is important because it is less invasive and can be performed without
      acetazolamide loading.

PMID- 26318362
TI  - Comparison of posterior lumbar interbody fusion (PLIF) with autogenous bone chips
      and PLIF with cage for treatment of double-level isthmic spondylolisthesis.
AB  - INTRODUCTION: Spondylolytic defects involving multiple vertebral levels are rare.
      It is reported that only 1.48% of patients with back pain were diagnosed with
      multi-level spondylolysis. The incidence of multiple-level spondylolisthesis is
      even rarer, so far there have been few reports of multi-level isthmic
      spondylolisthesis in the literature. The aim of this study is to evaluate
      clinical and radiological outcomes of two different fusion techniques for
      treatment of double-level isthmic spondylolisthesis. METHODS: Fifty-four patients
      who were managed surgically for treatment of double-level symptomatic isthmic
      spondylolisthesis were included in this study. Between May 2004 and September
      2012, 29 consecutive patients underwent posterior lumbar interbody fusion (PLIF)
      with autogenous bone chips (group I) at Foshan Hospital of Traditional Chinese
      Medicine, Guangdong, China. Between March 2005 and December 2013, 25 consecutive
      patients underwent PLIF with cage (group II) at Zhujiang Hospital of Southern
      Medical University, Guangdong, China. The mean follow-up periods were 27.2 and
      26.8 months, respectively. RESULTS: The mean VAS scores of back and leg pain
      significantly decreased from 7.2 to 2.2 and 5.8 to 2.1 in the group I and from
      7.0 to 1.9 and 6.1 to 1.8 in the group II, respectively. In the group I, mean ODI
      scores improved significantly from 54% to 14.2% and, in the group II, from 60% to
      12.6%. In both groups, VAS and ODI scores significantly changed from pre- to
      postoperatively (p<0.001), but postoperative outcome between groups was
      statistically not significant. Solid union was observed in 27 of 29 patients
      (89.6%) in the group I and in 22 of 25 patients (88%) in the group II, without
      statistically significant differences (p>0.05). In both groups, changes in disc
      height, degree of listhesis, and whole lumbar lordosis between the pre- and
      postoperative periods were significant. CONCLUSION: Clinical and functional
      outcomes demonstrate no significant differences between groups in treating back
      and leg pain of adult patients with double-level isthmic spondylolisthesis.

PMID- 26318363
TI  - Posterolateral fusion with interbody for lumbar spondylolisthesis is associated
      with less repeat surgery than posterolateral fusion alone.
AB  - OBJECTIVE: Posterior or transforaminal lumbar interbody fusions (PLIF/TLIF) may
      improve the outcomes in patients with lumbar spondylolisthesis. This study aims
      to compare outcomes after posterolateral fusion (PLF) only versus PLF with
      interbody fusion (PLF+PLIF/TLIF) in patients with spondylolisthesis. METHODS: We
      retrospectively reviewed103 patients who underwent first-time instrumented lumbar
      fusions for degenerative or isthmic spondylolisthesis. Anterior techniques and
      multilevel interbody fusions were excluded. All patients were followed for at
      least 2 years postoperatively. Clinical outcomes including back pain,
      radiculopathy, weakness, sensory deficits, and loss of bowel/bladder function
      were ascertained from clinic notes. Radiographic measures were calculated with
      Tillard percentage of spondylolisthesis. Reoperation for progression of
      degenerative disease, a primary endpoint, was indicated for all patients with (1)
      persistent or new-onset neurological symptoms; and (2) radiographic imaging that
      correlated with clinical presentation. RESULTS: Of the 103 patients, 56.31% were
      managed with PLF and 43.69% with PLF+PLIF/TLIF. On radiographic studies,
      spondylolisthesis improved by a mean of 13.06% after PLF+PLIF/TLIF versus 5.67%
      after PLF (p<0.001). In comparison to PLF+PLIF/TLIF, patients undergoing PLF
      experienced higher rates of postoperative improvement in back pain, sensory
      deficits, motor weakness, radiculopathy, and bowel/bladder difficulty; however,
      these differences did not reach statistical significance. The PLF cohort had a
      significantly higher incidence of reoperation (p=0.011) and
      pseudoarthrosis/instrumentation failure (p=0.043). In the logistical analyses,
      non-interbody fusion was the strongest predictor of reoperation for progression
      of degenerative disease. CONCLUSION: Compared to PLF only, PLF+PLIF/TLIF were
      statistically significantly associated with a greater correction of
      spondylolisthesis. Patients with interbody fusions were less likely to undergo
      reoperation for degenerative disease progression compared to non-interbody
      fusions. However, greater listhesis correction and decreased reoperation in the
      PLF+PLIF/TLIF cohort should be weighed with favorable clinical outcomes in the
      PLF cohort.

PMID- 26318364
TI  - Frequency-change in DPOAE evoked by 1 s/octave sweeping primaries in newborns and
      adults.
AB  - Distortion product otoacoustic emissions (DPOAE) in newborns and adults were
      evoked by sweeping primaries up and down in frequency at 1 s/octave. Sweeping up
      and down in frequency resulted in changes in the amplitude vs. frequency
      functions of the composite DPOAE and its two major components. In addition, DPOAE
      component phases differed slightly between the up- and down-swept conditions. The
      changes in amplitude vs. frequency functions were quantified using a covariate
      correlation technique, yielding single-valued estimates of the magnitude of the
      frequency changes. Separate analyses were performed for the entire DPOAE
      frequency range and split into low and high frequency ranges. There were
      consistent changes in newborn and adult composite DPOAEs and reflection
      components, but not generator components. Adults had significant frequency
      changes in the composite DPOAE for all frequency ranges and in the reflection
      component for the entire frequency range. Newborns had significant frequency
      change in the reflection component for all frequency ranges. Differences in
      frequency change between adults and newborns may stem from developmental changes
      in cochlear processing. Alignment of the component phase differences between the
      up- and down-swept conditions resulted in elimination of frequency-change in
      reconstructed composite DPOAEs. 

PMID- 26318365
TI  - Substrate topography: A valuable in vitro tool, but a clinical red herring for in
      vivo tenogenesis.
AB  - Controlling the cell-substrate interactions at the bio-interface is becoming an
      inherent element in the design of implantable devices. Modulation of cellular
      adhesion in vitro, through topographical cues, is a well-documented process that
      offers control over subsequent cellular functions. However, it is still unclear
      whether surface topography can be translated into a clinically functional
      response in vivo at the tissue/device interface. Herein, we demonstrated that
      anisotropic substrates with a groove depth of ~317nm and ~1988nm promoted human
      tenocyte alignment parallel to the underlying topography in vitro. However, the
      rigid poly(lactic-co-glycolic acid) substrates used in this study upregulated the
      expression of chondrogenic and osteogenic genes, indicating possible tenocyte
      trans-differentiation. Of significant importance is that none of the topographies
      assessed (~37nm, ~317nm and ~1988nm groove depth) induced extracellular matrix
      orientation parallel to the substrate orientation in a rat patellar tendon model.
      These data indicate that two-dimensional imprinting technologies are useful tools
      for in vitro cell phenotype maintenance, rather than for organised neotissue
      formation in vivo, should multifactorial approaches that consider both surface
      topography and substrate rigidity be established. STATEMENT OF SIGNIFICANCE:
      Herein, we ventured to assess the influence of parallel groves, ranging from nano
      to micro-level, on tenocytes response in vitro and on host response using a
      tendon and a subcutaneous model. In vitro analysis indicates that anisotropically
      ordered micro-scale grooves, as opposed to nano-scale grooves, maintain
      physiological cell morphology. The rather rigid PLGA substrates appeared to
      induce trans-differentiation towards chondrogenic and/or steogenic lineage, as
      evidence by TILDA gene analysis. In vivo data in both tendon and subcutaneous
      models indicate that none of the substrates induced bidirectional host cell and
      tissue growth. Collective, these observations indicate that two-dimensional
      imprinting technologies are useful tools for in vitro cell phenotype maintenance,
      rather than for directional neotissue formation, should multifactorial approaches
      that consider both surface topography and substrate rigidity be established.

PMID- 26318366
TI  - 3D plotting of growth factor loaded calcium phosphate cement scaffolds.
AB  - Additive manufacturing allows to widely control the geometrical features of
      implants. Recently, we described the fabrication of calcium phosphate cement
      (CPC) scaffolds by 3D plotting of a storable CPC paste based on water-immiscible
      carrier liquid. Plotting and hardening is conducted under mild conditions
      allowing the (precise and local) integration of biological components. In this
      study, we have developed a procedure for efficient loading of growth factors in
      the CPC scaffolds during plotting and demonstrated the feasibility of this
      approach. Bovine serum albumin (BSA) or vascular endothelial growth factor
      (VEGF), used as model proteins, were encapsulated in chitosan/dextran sulphate
      microparticles which could be easily mixed into the CPC paste in freeze-dried
      state. In order to prevent leaching of the proteins during cement setting,
      usually carried out by immersion in aqueous solutions, the plotted scaffolds were
      aged in water-saturated atmosphere (humidity). Setting in humidity avoided early
      loss of loaded proteins but provided sufficient amount of water to allow cement
      setting, as indicated by XRD analysis and mechanical testing in comparison to
      scaffolds set in water. Moreover, humidity-set scaffolds were characterised by
      altered, even improved properties: no swelling or crack formation was observed
      and accordingly, surface topography, total porosity and compressive modulus of
      the humidity-set scaffolds differed from those of the water-set counterparts.
      Direct cultivation of mesenchymal stem cells on the humidity-set scaffolds over
      21days revealed their cytocompatibility. Maintenance of the bioactivity of VEGF
      during the fabrication procedure was proven in indirect and direct culture
      experiments with endothelial cells. STATEMENT OF SIGNIFICANCE: Additive
      manufacturing techniques allow the fabrication of implants with defined
      architecture (inner pore structure and outer shape). Especially printing
      technologies conducted under mild conditions allow additionally the (spatially
      controlled) integration of biological components such as drugs or growth factors.
      That enables the generation of individualized implants which can better meet the
      requirements of a patient and of tissue engineering constructs. To our knowledge,
      simultaneous printing of biological components was up to now only described for
      hydrogel/biopolymer-based materials which suffer from poor mechanical properties.
      In contrast, we have developed a procedure (based on 3D plotting of a calcium
      phosphate cement paste) for the fabrication of designed and growth factor loaded
      calcium-phosphate-based scaffolds applicable for bone regeneration.

PMID- 26318367
TI  - Putting age-related task activation into large-scale brain networks: A meta
      analysis of 114 fMRI studies on healthy aging.
AB  - Normal aging is associated with cognitive decline and underlying brain
      dysfunction. Previous studies concentrated less on brain network changes at a
      systems level. Our goal was to examine these age-related changes of fMRI-derived
      activation with a common network parcellation of the human brain function,
      offering a systems-neuroscience perspective of healthy aging. We conducted a
      series of meta-analyses on a total of 114 studies that included 2035 older adults
      and 1845 young adults. Voxels showing significant age-related changes in
      activation were then overlaid onto seven commonly referenced neuronal networks.
      Older adults present moderate cognitive decline in behavioral performance during
      fMRI scanning, and hypo-activate the visual network and hyper-activate both the
      frontoparietal control and default mode networks. The degree of increased
      activation in frontoparietal network was associated with behavioral performance
      in older adults. Age-related changes in activation present different network
      patterns across cognitive domains. The systems neuroscience approach used here
      may be useful for elucidating the underlying network mechanisms of various brain
      plasticity processes during healthy aging. 

PMID- 26318368
TI  - Evaluation of low-grade glioma structural changes after chemotherapy using DTI
      based histogram analysis and functional diffusion maps.
AB  - OBJECTIVES: To explore the role of diffusion tensor imaging (DTI)-based histogram
      analysis and functional diffusion maps (fDMs) in evaluating structural changes of
      low-grade gliomas (LGGs) receiving temozolomide (TMZ) chemotherapy. METHODS:
      Twenty-one LGG patients underwent 3T-MR examinations before and after three and
      six cycles of dose-dense TMZ, including 3D-fluid-attenuated inversion recovery
      (FLAIR) sequences and DTI (b = 1000 s/mm(2), 32 directions). Mean diffusivity
      (MD), fractional anisotropy (FA), and tensor-decomposition DTI maps (p and q)
      were obtained. Histogram and fDM analyses were performed on co-registered
      baseline and post-chemotherapy maps. DTI changes were compared with modifications
      of tumour area and volume [according to Response Assessment in Neuro-Oncology
      (RANO) criteria], and seizure response. RESULTS: After three cycles of TMZ, 20/21
      patients were stable according to RANO criteria, but DTI changes were observed in
      all patients (Wilcoxon test, P <= 0.03). After six cycles, DTI changes were more
      pronounced (P <= 0.005). Seventy-five percent of patients had early seizure
      response with significant improvement of DTI values, maintaining stability on
      FLAIR. Early changes of the 25th percentiles of p and MD predicted final volume
      change (R(2) = 0.614 and 0.561, P < 0.0005, respectively). TMZ-related changes
      were located mainly at tumour borders on p and MD fDMs. CONCLUSIONS: DTI-based
      histogram and fDM analyses are useful techniques to evaluate the early effects of
      TMZ chemotherapy in LGG patients. KEY POINTS: * DTI helps to assess the efficacy
      of chemotherapy in low-grade gliomas. * Histogram analysis of DTI metrics
      quantifies structural changes in tumour tissue. * Functional diffusion maps
      (fDMs) spatially localize the changes of DTI metrics. * Changes in DTI histograms
      and fDMs precede changes in conventional MRI. * Early changes in DTI histograms
      and fDMs correlate with seizure response.

PMID- 26318369
TI  - Assessment of Silent T1-weighted head imaging at 7 T.
AB  - OBJECTIVES: This study aimed to assess the performance of a "Silent" zero time of
      echo (ZTE) sequence for T1-weighted brain imaging using a 7 T MRI system.
      METHODS: The Silent sequence was evaluated qualitatively by two
      neuroradiologists, as well as quantitatively in terms of tissue contrast,
      homogeneity, signal-to-noise ratio (SNR) and acoustic noise. It was compared to
      conventional T1-weighted imaging (FSPGR). Adequacy for automated segmentation was
      evaluated in comparison with FSPGR acquired at 7 T and 1.5 T. Specific absorption
      rate (SAR) was also measured. RESULTS: Tissue contrast and homogeneity in Silent
      were remarkable in deep brain structures and in the occipital and temporal lobes.
      Mean tissue contrast was significantly (p < 0.002) higher in Silent (0.25) than
      in FSPGR (0.11), which favoured automated tissue segmentation. On the other hand,
      Silent images had lower SNR with respect to conventional imaging: average SNR of
      FSPGR was 2.66 times that of Silent. Silent images were affected by artefacts
      related to projection reconstruction, which nevertheless did not compromise the
      depiction of brain tissues. Silent acquisition was 35 dB(A) quieter than FSPGR
      and less than 2.5 dB(A) louder than ambient noise. Six-minute average SAR was <2
      W/kg. CONCLUSIONS: The ZTE Silent sequence provides high-contrast T1-weighted
      imaging with low acoustic noise at 7 T. KEY POINTS: * "Silent" is an MRI
      technique allowing zero time of echo acquisition * Its feasibility and
      performance were assessed on a 7 T MRI system * Image quality in several regions
      was higher than in conventional techniques * Imaging acoustic noise was
      dramatically reduced compared with conventional imaging * "Silent" is suitable
      for T1-weighted head imaging at 7 T.

PMID- 26318370
TI  - Non-invasive MR assessment of macroscopic and microscopic vascular abnormalities
      in the rectal tumour-surrounding mesorectum.
AB  - OBJECTIVES: To evaluate the MRI macroscopic and microscopic parameters of
      mesorectal vasculature in rectal cancer patients. METHODS: Thirteen patients with
      rectal adenocarcinoma underwent a dynamic contrast-enhanced MRI at 1.5 T using a
      blood pool agent at the primary staging. Mesorectal macrovascular features, i.e.,
      the number of vascular branches, average diameter and length, were assessed from
      baseline-subtracted post-contrast images by two independent readers. Mesorectal
      microvascular function was investigated by means of area under the enhancement
      time curve (AUC). Histopathology served as reference standard of the tumour
      response to CRT. RESULTS: The average vessel branching in the mesorectum around
      the tumour and normal rectal wall was 8.2 +/- 3.8 and 1.7 +/- 1.3, respectively
      (reader1: p = 0.001, reader2: p = 0.002). Similarly, the tumour-surrounding
      mesorectum displayed circa tenfold elevated AUC (p = 0.01). Interestingly,
      patients with primary node involvement had a twofold higher number of
      macrovascular branches compared to those with healthy nodes (reader1: p = 0.005
      and reader2: p = 0.03). A similar difference was observed between good and poor
      responders to CRT, whose tumour-surrounding mesorectum displayed 10.7 +/- 3.4 and
      5.6 +/- 1.5 vessels, respectively (reader1/reader2: p = 0.02). CONCLUSIONS: We
      showed at baseline MRI of rectal tumours a significantly enhanced macrovascular
      structure and microvascular function in rectal tumour-surrounding mesorectum, and
      the association of primary mesorectal macrovascular parameters with node
      involvement and therapy response. KEY POINTS: * Vascular MRI reveals
      macrovascular and microvascular abnormalities in the rectal tumour-surrounding
      mesorectum. * Formation of highly vascular stroma precedes the actual tumour
      invasion. * High macrovascular parameters are associated with node involvement. *
      Mesorectal vascular network differs for good and poor responders.

PMID- 26318371
TI  - The impact of MRI combined with visual rating scales on the clinical diagnosis of
      dementia: a prospective study.
AB  - OBJECTIVES: Dementia is foremost a clinical diagnosis. However, in diagnosing
      dementia, it is advocated to perform at least one neuroimaging study. This has
      two purposes: to rule out potential reversible dementia (PRD), and to help
      determine the dementia subtype. Our first goal was to establish if MRI combined
      with visual rating scales changes the clinical diagnosis. The second goal was to
      demonstrate if MRI contributes to a geriatrician's confidence in the diagnosis.
      METHODS: The dementia subtype was determined prior to and after MRI. Scoring
      scales used were: global cortical atrophy (GCA), medial temporal atrophy (MTA),
      and white matter hyperintensity measured according to the Fazekas scale. The
      confidence level of the geriatrician was determined using a visual analogue
      scale. RESULTS: One hundred and thirty-five patients were included. After MRI,
      the diagnosis changed in 23.7 % (CI 17.0 %-31.1 %) of patients. Change was due to
      vascular aetiology in 13.3 % of patients. PRD was found in 2.2 % of all patients.
      The confidence level in the diagnosis increased significantly after MRI (p =
      0.001). CONCLUSIONS: MRI, combined with visual rating scales, has a significant
      impact on dementia subtype diagnosis and on a geriatrician's confidence in the
      final diagnosis. KEY POINTS: * MRI with visual rating scales changes the dementia
      subtype diagnosis significantly. * MRI is essential in demonstrating vascular
      disease as a cause of dementia. * All suspected dementia patients should undergo
      an MRI with visual rating scales. * MRI improves a geriatrician's confidence in
      the diagnosis of the dementia subtype. * MRI remains essential during the workup
      of dementia to exclude reversible causes.

PMID- 26318372
TI  - Percutaneous osteosynthesis in the pelvis in cancer patients.
AB  - PURPOSE: Screw fixation (osteosynthesis) can be performed percutaneously by
      interventional radiologists. We report our experience in cancer patients.
      MATERIAL/METHODS: We retrospectively reviewed all cases of percutaneous
      osteosynthesis (PO) of the pelvic ring and proximal femur performed in our
      hospital. PO were performed for fracture palliation or for osteolytic metastases
      consolidation. Screws were inserted under CT- or cone-beam CT- guidance and
      general anaesthesia. Patients were followed-up with pelvic-CT and medical
      consultation at 1 month, then every 3 months. For fractures, the goal was pain
      palliation and for osteolytic metastases, pathologic fracture prevention.
      RESULTS: Between February 2010 and August 2014, 64 cancer patients were treated
      with PO. Twenty-one patients had PO alone for 33 painful fractures (13 bone
      insufficiency, 20 pathologic fractures). The pain was significantly improved at 1
      month (VAS score = 20/100 vs. 80/100). In addition, 43 cancer patients were
      preventively consolidated using PO plus cementoplasty for 45 impending pathologic
      fractures (10 iliac crests, 35 proximal femurs). For the iliac crests, no
      fracture occurred (median-FU = 75 days). For the proximal femurs, 2 pathological
      fractures occurred (fracture rate = 5.7 %, median-FU = 205 days). CONCLUSION: PO
      is a new tool in the therapeutic arsenal of interventional radiologists for bone
      pain management. KEY POINTS: * Screw fixation (osteosynthesis) can be performed
      percutaneously by interventional radiologists. * CT- or CBCT-guidance results in
      high technical success rates for screw placement. * This minimally invasive
      technique avoids extensive surgical exposure in bone cancer patients. *
      Osteosynthesis provides pain relief for bone-insufficiency fractures and for
      pathologic fractures. * Osteosynthesis plus cementoplasty provide prophylactic
      consolidation of impending pathological fractures.

PMID- 26318374
TI  - Skin lesion in a critically ill man.

PMID- 26318373
TI  - Patient and Family Caregivers' Experiences of Living With a Jejunostomy Feeding
      Tube After Surgery for Esophagogastric Cancer.
AB  - BACKGROUND: Jejunostomy feeding tubes (JFTs) can be used to provide nutrition
      support to patients who have had surgery for esophagogastric cancer. Although
      previous research reports how patients cope with a gastrostomy tube, little is
      known about the impact of having a JFT. The aim of this qualitative study was to
      explore how patients and their informal caregivers experience living with a JFT
      in the first months following surgery. METHODS: Participants were purposively
      sampled from a cohort of patients recruited to a trial investigating home enteral
      nutrition vs standard care after esophagogastric surgery for cancer. The sampling
      framework considered age, sex, and marital status. Informal caregivers were also
      invited to participate. Interviews were audio recorded, transcribed verbatim, and
      anonymized. Inductive thematic analysis was used to identify key themes related
      to living with a JFT. RESULTS: Fifteen patient interviews were conducted; 8 also
      included a family caregiver. Analysis of the data resulted in 2 main themes:
      "challenges" and "facilitators" when living with a JFT. While "physical effects,"
      "worries" and "impact on routine" were the main challenges, "support,"
      "adaptation" and "perceived benefit" were what motivated continuation of the
      intervention. CONCLUSION: Findings suggest that participants coped well with a
      JFT, describing high levels of compliance with stoma care and the feeding
      regimen. Nonetheless, disturbed sleep patterns and stoma-related problems proved
      troublesome. A better understanding of these practical challenges, from the
      patient and family caregiver perspective, should guide healthcare teams in
      providing proactive support to avoid preventable problems.

PMID- 26318375
TI  - Functional movement disorder: a long journey to diagnosis.
AB  - A 61-year-old man presented to a country clinic with involuntary orofacial
      movements and progressive cognitive decline, causing significant disability and
      psychosocial distress. Review of records uncovered a 7-year history of
      presentations to several specialties, including memory clinics, neurology,
      internal medicine and emergency departments, with varied symptoms, extensive
      complex work up and inconclusive diagnosis. Comprehensive review at our hospital
      highlighted inconsistent neurological signs, fluctuating cognition and
      psychosocial stressors, which preceded symptom onset, leading to the diagnosis of
      a functional movement disorder (FMD), which subsequently improved with relaxation
      therapy, cognitive-behavioural therapy and physiotherapy. We illustrate a variety
      of somatic symptoms, diagnostic clues and management outcomes for FMDs, and the
      importance of diagnostic criteria to minimise costly, time-consuming and
      ultimately unnecessary tests of exclusion. 

PMID- 26318376
TI  - Roles, tasks and educational functions of postgraduate programme directors: a
      qualitative study.
AB  - BACKGROUND: A programme director is often required to organise postgraduate
      medical education. This leadership role can include educational as well as
      managerial duties. Only a few published studies have explored programme
      directors' own perceptions of their role. There is a need to explore the use of
      theoretical frameworks to improve the understanding of educational roles.
      OBJECTIVE: To explore programme directors' own perceptions of their role in terms
      of tasks and functions, and to relate these roles to the theoretical framework
      developed by Bolman and Deal. METHODS: Semi-structured interviews were conducted
      with 17 programme directors between February and August 2013. The data were
      subjected to content analysis using a deductive approach. RESULTS: The various
      roles and tasks included by participants in their perceptions of their work could
      be categorised within the framework of functions described by Bolman and Deal.
      These included: structuring the education (structural function); supporting
      individuals and handling relations (human resource function); negotiating between
      different interests (political function); and influencing the culture at the
      departmental level (symbolic function). The functions most often emphasised by
      participants were the structural and human resource functions. Some tasks
      involved several functions which varied over time. CONCLUSIONS: Programme
      directors' own perceptions of their roles, tasks and functions varied widely. The
      theoretical framework of Bolman and Deal might be helpful when explaining and
      developing these roles.

PMID- 26318377
TI  - First Do No Harm: Prevention Strategies for Influenza Season.

PMID- 26318378
TI  - Pediatric Post-Traumatic Stress Disorder.

PMID- 26318379
TI  - Roseivirga marina sp. nov., isolated from seawater.
AB  - Strain PSRT was isolated from seawater of the Pacific Ocean. Cells of the strain
      were Gram-stain-negative, strictly aerobic, rod-shaped and motile by gliding.
      Growth was observed at 4-40  degrees C (optimum 25-30  degrees C), at pH 6.0-9.5
      (optimum pH 7.0-7.5) and with 0.5-8 % (w/v) NaCl (optimum 2-3 %). The major fatty
      acids were iso-C15 : 1 G (18.9 %), iso-C15 : 0 (26.3 %) and iso-C17 : 0 3-OH
      (17.9 %). The predominant isoprenoid quinone was MK-7, and the DNA G+C content
      was 49.3 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated
      that strain PSRT was most closely related to Roseivirga spongicola UST030701-084T
      (96.9 % 16S rRNA gene sequence similarity), and they formed a distinct clade in
      neighbour-joining, maximum-likelihood and maximum-parsimony phylogenetic trees
      with significant bootstrap supports. Based on phenotypic, chemotaxonomic and
      phylogenetic characteristics, strain PSRT represents a novel species of the genus
      Roseivirga, for which the name Roseivirga marina sp. nov. is proposed. The type
      strain is PSRT ( = MCCC 1K00459T = KCTC 42444T).

PMID- 26318380
TI  - Chlormequat poisoning is not without risk: Examination of seven fatal cases.
AB  - Chlormequat chloride is a plant growth regulator. Chlormequat poisoning
      clinically resembles anticholinesterase insecticide poisoning. The cholinergic
      symptoms result from direct action on nicotinic and muscarinic receptors and not
      from inhibition of the cholinesterase activity. This case series confirms the
      extreme gravity of chlomequat poisoning with a risk of death in the hour
      following ingestion. 

PMID- 26318381
TI  - Clinical Practice Guidelines for the Management of Gastroesophageal Reflux and
      Gastroesophageal Reflux Disease: Birth to 1 Year of Age.

PMID- 26318382
TI  - Understanding reactivity and regioselectivity in Diels-Alder reactions of a sugar
      derived dienophile bearing two competing EWGs. An experimental and computational
      study.
AB  - The effect of an extra EWG in the reactivity and regioselectivity in Diels-Alder
      reactions of beta-cyanolevoglucosenone and 4 different dienes was studied by a
      joint computational and experimental study. Conceptual DFT analysis successfully
      predicted an important enhancement in the reactivity, and correctly anticipated
      the regioselectivity in the reactions with isoprene. However, this static
      treatment failed when dealing the regiochemical preference of the reactions
      involving a substituted anthracene as diene. MPW1K/6-31G* calculations correctly
      reproduced the experimental observations. Based on the collected data, we found
      that when dealing with dienes and dienophiles with no clear electronically
      activated position, the ease of pyramidalization of the interacting atoms
      dictates the regioselectivity of the DA reaction. 

PMID- 26318383
TI  - Evaluation of super-resolution performance of the K2 electron-counting camera
      using 2D crystals of aquaporin-0.
AB  - The K2 Summit camera was initially the only commercially available direct
      electron detection camera that was optimized for high-speed counting of primary
      electrons and was also the only one that implemented centroiding so that the
      resolution of the camera can be extended beyond the Nyquist limit set by the
      physical pixel size. In this study, we used well-characterized two-dimensional
      crystals of the membrane protein aquaporin-0 to characterize the performance of
      the camera below and beyond the physical Nyquist limit and to measure the
      influence of electron dose rate on image amplitudes and phases. 

PMID- 26318384
TI  - A randomised, double-blind, phase III study comparing SB2, an infliximab
      biosimilar, to the infliximab reference product Remicade in patients with
      moderate to severe rheumatoid arthritis despite methotrexate therapy.
AB  - OBJECTIVES: To compare the efficacy, safety, immunogenicity and pharmacokinetics
      (PK) of SB2 to the infliximab reference product (INF) in patients with moderate
      to severe rheumatoid arthritis (RA) despite methotrexate therapy. METHODS: This
      is a phase III, randomised, double-blind, multinational, multicentre parallel
      group study. Patients with moderate to severe RA despite methotrexate therapy
      were randomised in a 1:1 ratio to receive either SB2 or INF of 3 mg/kg. The
      primary end point was the American College of Rheumatology 20% (ACR20) response
      at week 30. Inclusion of the 95% CI of the ACR20 response difference within a +/
      15% margin was required for equivalence. RESULTS: 584 subjects were randomised
      into SB2 (N=291; 290 analysed) or INF (N=293). The ACR20 response at week 30 in
      the per-protocol set was 64.1% in SB2 versus 66.0% in INF. The adjusted rate
      difference was -1.88% (95% CI -10.26% to 6.51%), which was within the predefined
      equivalence margin. Other efficacy outcomes such as ACR50/70, disease activity
      score measured by 28 joints and European League against Rheumatism response were
      similar between SB2 and INF. The incidence of treatment-emergent adverse events
      was comparable (57.6% in SB2 vs 58.0% in INF) as well as the incidence of
      antidrug antibodies (ADA) to infliximab up to week 30 (55.1% in SB2 vs 49.7% in
      INF). The PK profile was similar between SB2 and INF. Efficacy, safety and PK by
      ADA subgroup were comparable between SB2 and INF. CONCLUSIONS: SB2 was equivalent
      to INF in terms of ACR20 response at week 30. SB2 was well tolerated with a
      comparable safety profile, immunogenicity and PK to INF. TRIAL REGISTRATION
      NUMBER: NCT01936181.

PMID- 26318385
TI  - Tuberculosis and other opportunistic infections in tofacitinib-treated patients
      with rheumatoid arthritis.
AB  - OBJECTIVES: To evaluate the risk of opportunistic infections (OIs) in patients
      with rheumatoid arthritis (RA) treated with tofacitinib. METHODS: Phase II, III
      and long-term extension clinical trial data (April 2013 data-cut) from the
      tofacitinib RA programme were reviewed. OIs defined a priori included
      mycobacterial and fungal infections, multidermatomal herpes zoster and other
      viral infections associated with immunosuppression. For OIs, we calculated crude
      incidence rates (IRs; per 100 patient-years (95% CI)); for tuberculosis (TB)
      specifically, we calculated rates stratified by patient enrolment region
      according to background TB IR (per 100 patient-years): low (<=0.01), medium
      (>0.01 to <=0.05) and high (>0.05). RESULTS: We identified 60 OIs among 5671
      subjects; all occurred among tofacitinib-treated patients. TB (crude IR 0.21, 95%
      CI of (0.14 to 0.30)) was the most common OI (n=26); median time between drug
      start and diagnosis was 64 weeks (range 15-161 weeks). Twenty-one cases (81%)
      occurred in countries with high background TB IR, and the rate varied with
      regional background TB IR: low 0.02 (0.003 to 0.15), medium 0.08 (0.03 to 0.21)
      and high 0.75 (0.49 to 1.15). In Phase III studies, 263 patients diagnosed with
      latent TB infection were treated with isoniazid and tofacitinib concurrently;
      none developed TB. For OIs other than TB, 34 events were reported (crude IR 0.25
      (95% CI 0.18 to 0.36)). CONCLUSIONS: Within the global tofacitinib RA development
      programme, TB was the most common OI reported but was rare in regions of low and
      medium TB incidence. Patients who screen positive for latent TB can be treated
      with isoniazid during tofacitinib therapy.

PMID- 26318386
TI  - The Trail Making Test.
AB  - The Trail Making Test (TMT) is used as an indicator of visual scanning,
      graphomotor speed, and executive function. The aim of this study was to examine
      the TMT relationships with several neuropsychological measures and to provide
      normative data in community-dwelling participants of 55 years and older. A
      population-based Spanish-speaking sample of 2,564 participants was used. The TMT,
      Symbol Digit Test, Stroop Color-Word Test, Digit Span Test, Verbal Fluency tests,
      and the MacQuarrie Test for Mechanical Ability tapping subtest were administered.
      Exploratory factor analyses and regression lineal models were used. Normative
      data for the TMT scores were obtained. A total of 1,923 participants (76.3%)
      participated, 52.4% were women, and the mean age was 66.5 years (Digit Span =
      8.0). The Symbol Digit Test, MacQuarrie Test for Mechanical Ability tapping
      subtest, Stroop Color-Word Test, and Digit Span Test scores were associated in
      the performance of most TMT scores, but the contribution of each measure was
      different depending on the TMT score. Normative tables according to significant
      factors such as age, education level, and sex were created. Measures of visual
      scanning, graphomotor speed, and visuomotor processing speed were more related to
      the performance of the TMT-A score, while working memory and inhibition control
      were mainly associated with the TMT-B and derived TMT scores.

PMID- 26318387
TI  - Associations Between Pre-Implant Psychosocial Factors and Spinal Cord Stimulation
      Outcome: Evaluation Using the MMPI-2-RF.
AB  - Spinal cord stimulation (SCS) has variable effectiveness in controlling chronic
      pain. Previous research has demonstrated that psychosocial factors are associated
      with diminished results of SCS. The objective of this investigation is to examine
      associations between pre-implant psychological functioning as measured by the
      Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) and
      SCS outcomes. SCS candidates at two sites (total N = 319) completed the MMPI-2-RF
      and measures of pain, emotional distress, and functional ability as part of a pre
      implant psychological evaluation. At an average of 5 months post-implant,
      patients completed the measures of pain and emotional distress a second time.
      Poorer SCS outcomes and poorer patient satisfaction were associated with higher
      pre-implant MMPI-2-RF scores on scales used to assess emotional dysfunction,
      somatic/cognitive complaints, and interpersonal problems. Ways through which pre
      implant psychological evaluations of spinal cord stimulator candidates can be
      informed by MMPI-2-RF findings are discussed.

PMID- 26318388
TI  - Uric acid and xanthine oxidase in heart failure - Emerging data and therapeutic
      implications.
AB  - The role of hyperuricaemia as cardiovascular risk factor has exhaustingly been
      debated for decades. While the association of elevated uric acid (UA) levels with
      increased mortality risk as convincingly been shown, the question whether UA is
      independently predictive of just a related effect within a more complex risk
      factor profile (including metabolic, inflammatory and haemodynamic risk factors)
      is still a matter of dispute. In heart failure the independent prognostic and
      functional impact of elevated UA has not only been shown but also the
      pathophysiologic mechanism(s) and the potential of targeted therapeutic
      interventions have been investigated in some detail. The emerging picture
      suggests the increased activity of the enzyme xanthine oxidase (XO) with
      corresponding increased production of free oxygen radical (ROS) as a main
      underlying principle with the resulting increase in UA levels being mostly a
      marker of this up-regulated pathway. While this concept will not diminish the
      value of UA as a prognostic marker, it provides the basis for a novel metabolic
      treatment option and the means to identify those patients most eligible for this
      tailored therapy. This review will summarize the recent evidence on XO as a novel
      and promising therapeutic target in heart failure. 

PMID- 26318389
TI  - Uric acid and coronary artery disease: An elusive link deserving further
      attention.
AB  - Uric acid is the final product of purine metabolism. Classically it is recognized
      as the cause of gouty arthritis and kidney stones. Western civilization has
      increased serum levels of uric acid which is no longer considered a benign plasma
      solute. It has been postulated and recently demonstrated that it can penetrate
      cell membrane and exerts damaging intracellular actions such as oxidation and
      inflammation. These observations have stimulated several epidemiological
      researches suggesting that hyperuricemia is linked or even provokes hypertension
      and coronary artery disease. In this review we summarize the current evidences
      regarding uric acid which contribute in the pathophysiology of coronary artery
      disease. 

PMID- 26318390
TI  - Green tea consumption and risk of cardiovascular and ischemic related diseases: A
      meta-analysis.
AB  - BACKGROUND: The effects of green tea intake on risk of cardiovascular disease
      (CVD) have not been well-defined. The aim of this meta-analysis was to evaluate
      the association between green tea consumption, CVD, and ischemic related
      diseases. METHODS: All observational studies and randomized trials that were
      published through October 2014 and that examined the association between green
      tea consumption and risk of cardiovascular and ischemic related diseases as the
      primary outcome were included in this meta-analysis. The quality of the included
      studies was evaluated according to the Cochrane Handbook 5.0.2 quality evaluation
      criteria. RESULTS: A total of 9 studies including 259,267 individuals were
      included in the meta-analysis. The results showed that those who didn't consume
      green tea had higher risks of CVD (OR=1.19, 95% CI: 1.09-1.29), intracerebral
      hemorrhage (OR=1.24, 95% CI: 1.03-1.49), and cerebral infarction (OR=1.15, 95%
      CI: 1.01-1.30) compared to <1 cup green tea per day. Those who drank 1-3 cups of
      green tea per day had a reduced risk of myocardial infarction (OR=0.81, 95% CI:
      0.67-0.98) and stroke (OR=0.64, 95% CI: 0.47-0.86) compared to those who drank <1
      cup/day. Similarly, those who drank >=4 cups/day had a reduced risk of myocardial
      infarction compared to those who drank <1 cup/day (OR=0.68, 95% CI: 0.56-0.84).
      Those who consumed >=10 cups/day of green tea were also shown to have lower LDL
      compared to the <3 cups/day group (MD=-0.90, 95% CI: -0.95 to -0.85).
      CONCLUSIONS: Our meta-analysis provides evidence that consumption of green tea is
      associated with favorable outcomes with respect to risk of cardiovascular and
      ischemic related diseases.

PMID- 26318391
TI  - GABA-ergic interneurons involved in transcallosal inhibition of the visual
      cortices in vivo in mice.
AB  - In the current study we investigated the role of the corpus callosum,
      particularly the gamma-aminobutyric acid-ergic (GABAergic) projection neurons
      involved in interhemispheric inhibition (IHI). In order to explore IHI in primary
      visual cortices, we adopted a protocol whereby we performed a direct current
      lesion of the unilateral primary visual cortex with or without posterior
      callosotomy, and used two-photon Ca(2+)in vivo imaging on the opposite unaffected
      region to detect neural activities in mice. Following this procedure, the numbers
      of vesicular GABAergic transporters (VGATs) and GABAergic interneurons in the
      unaffected primary cortex were determined using immunofluorescence staining.
      Results indicated that following unilateral visual cortical lesioning without
      callosotomy, the neuronal Ca(2+) activities in the opposite side were
      significantly increased. However, the neuronal activities of the unaffected
      visual cortex in animals with unilateral cortical lesion with callosotomy were
      not significantly different. Additionally, there was no significant difference in
      the numbers of GABAergic interneurons in the unaffected region between each
      group, while the number of VGATs in the unaffected region was significantly
      decreased following unilateral visual cortical lesion without callosotomy, which
      was unchanged once with callosotomy. Finally, callosotomy alone without cortical
      lesioning produced no change in neuronal activities, the number of GABAergic
      interneurons or VGATs. Our results demonstrate that IHI between the homologous
      primary visual cortices occurs via the corpus callosum, and further indicate the
      important involvement of long-range GABAergic interneurons in transcallosal
      inhibition. 

PMID- 26318392
TI  - Improving Outcomes in Patients With Refractory Idiopathic and Neurogenic Detrusor
      Overactivity: Management Strategies.
AB  - Neurogenic detrusor overactivity (NDO) is a lower urinary tract dysfunction
      commonly seen in rehabilitation settings. The emotional, medical, and financial
      consequences of NDO can be substantial and management typically requires a
      multidisciplinary team approach. Physiatrists need to be able to identify
      patients who require referral to specialists for diagnostic testing or higher
      tiered treatment and need to engender open lines of communication between their
      patients and all treating clinicians. This requires an understanding of the
      evaluation, diagnosis, and treatment of neurogenic lower urinary tract
      dysfunctions. 

PMID- 26318393
TI  - Reliability and validity of the Four Square Step Test in children with cerebral
      palsy and Down syndrome.
AB  - Little is known about the measurement properties of clinical tests of stepping in
      different directions for children with cerebral palsy (CP) and Down syndrome
      (DS). The ability to step in various directions is an important balance skill for
      daily life. Standardized testing of this skill can yield important information
      for therapy planning. This observational methodological study was aimed at
      defining the relative and absolute reliability, minimal detectable difference,
      and concurrent validity with the Timed Up-&-Go (TUG) of the Four Square Step Test
      (FSST) for children with CP and DS. Thirty children, 16 with CP and 14 with DS,
      underwent repeat testing 2 weeks apart on the FSST by 3 raters. TUG was
      administered on the second test occasion. Intraclass correlation coefficients
      (ICC [1,1] and [3,1]) with 95% confidence intervals, standard error of
      measurement (SEM), minimal detectable difference (MDD) and the Spearman rank
      correlation coefficient were computed. The FSST demonstrated excellent interrater
      reliability (ICC=.79; 95% CI: .66, .89) and high positive correlation with the
      TUG (r=.74). Test-retest reliability estimates varied from moderate to excellent
      among the 3 raters (.54, .78 and .89 for raters 1, 2 and 3, respectively). SEM
      and MDD were calculated at 1.91s and 5.29s, respectively. Scores on the FSST of
      children with CP and DS between 5 and 12 years of age are reliable and valid. 

PMID- 26318394
TI  - [Definition of botulinum toxin failure in neurogenic detrusor overactivity:
      Preliminary results of the DETOX survey].
AB  - OBJECTIVE: There is currently no guideline regarding the management of neurogenic
      detrusor overactivity (NDO) refractory to intra-detrusor botulinum toxin
      injections. The primary objective of the present study was to find a consensus
      definition of failure of botulinum toxin intra-detrusor injections for NDO. The
      secondary objective was to report current trends in the managment of NDO
      refractory to botulinum toxin. METHODS: A survey was created, based on data drawn
      from current literature, and sent via e-mail to all the experts form the Group
      for research in neurourology in french language (GENULF) and from the comittee of
      neurourology of the French urological association (AFU). The experts who did not
      answer to the first e-mail were contacted again twice. Main results from the
      survey are presented and expressed as numbers and proportions. RESULTS: Out of
      the 42 experts contacted, 21 responded to the survey. Nineteen participants
      considered that the definition of failure should be a combination of clinical and
      urodynamics criteria. Among the urodynamics criteria, the persistence of a
      maximum detrusor pressure>40 cm H2O was the most supported by the experts (18/21,
      85%). According to the vast majority of participants (19/21, 90.5%), the impact
      of injections on urinary incontinence should be included in the definition of
      failure. Regarding the management, most experts considered that the first line
      treatment in case of failure of a first intra-detrusor injection of Botox((r))
      200 U should be a repeat injection of Botox((r)) at a higher dosage (300 U)
      (15/20, 75%), regardless of the presence or not of urodynamics risk factors of
      upper tract damage (16/20, 80%). CONCLUSION: This work has provided a first
      overview of the definition of failure of intra-detrusor injections of botulinum
      toxin in the management of NDO. For 90.5% of the experts involved, the definition
      of failure should be clinical and urodynamic and most participants (75%)
      considered that, in case of failure of a first injection of Botox((r)) 200 U,
      repeat injection of Botox((r)) 300 U should be the first line treatment.

PMID- 26318395
TI  - Development of the CRISPR/Cas9 System for Targeted Gene Disruption in Aspergillus
      fumigatus.
AB  - Low rates of homologous recombination have broadly encumbered genetic studies in
      the fungal pathogen Aspergillus fumigatus. The CRISPR/Cas9 system of bacteria has
      recently been developed for targeted mutagenesis of eukaryotic genomes with high
      efficiency and, importantly, through a mechanism independent of homologous repair
      machinery. As this new technology has not been developed for use in A. fumigatus,
      we sought to test its feasibility for targeted gene disruption in this organism.
      As a proof of principle, we first demonstrated that CRISPR/Cas9 can indeed be
      used for high-efficiency (25 to 53%) targeting of the A. fumigatus polyketide
      synthase gene (pksP), as evidenced by the generation of colorless (albino)
      mutants harboring the expected genomic alteration. We further demonstrated that
      the constitutive expression of the Cas9 nuclease by itself is not deleterious to
      A. fumigatus growth or virulence, thus making the CRISPR system compatible with
      studies involved in pathogenesis. Taken together, these data demonstrate that
      CRISPR can be utilized for loss-of-function studies in A. fumigatus and has the
      potential to bolster the genetic toolbox for this important pathogen. 

PMID- 26318396
TI  - A MORN Repeat Protein Facilitates Protein Entry into the Flagellar Pocket of
      Trypanosoma brucei.
AB  - The parasite Trypanosoma brucei lives in the bloodstream of infected mammalian
      hosts, fully exposed to the adaptive immune system. It relies on a very high rate
      of endocytosis to clear bound antibodies from its cell surface. All endo- and
      exocytosis occurs at a single site on its plasma membrane, an intracellular
      invagination termed the flagellar pocket. Coiled around the neck of the flagellar
      pocket is a multiprotein complex containing the repeat motif protein T. brucei
      MORN1 (TbMORN1). In this study, the phenotypic effects of TbMORN1 depletion in
      the mammalian-infective form of T. brucei were analyzed. Depletion of TbMORN1
      resulted in a rapid enlargement of the flagellar pocket. Dextran, a
      polysaccharide marker for fluid phase endocytosis, accumulated inside the
      enlarged flagellar pocket. Unexpectedly, however, the proteins concanavalin A and
      bovine serum albumin did not do so, and concanavalin A was instead found to
      concentrate outside it. This suggests that TbMORN1 may have a role in
      facilitating the entry of proteins into the flagellar pocket. 

PMID- 26318397
TI  - Unfolded Protein Response Pathways in Bloodstream-Form Trypanosoma brucei?
AB  - The unfolded protein response (UPR) is a stress mechanism to cope with misfolded
      proteins in the early secretory pathway, the hallmark being transcriptional
      upregulation of endoplasmic reticulum (ER) molecular chaperones such as BiP and
      protein disulfide isomerase. Despite the lack of transcriptional regulation and
      the absence of the classical UPR machinery, African trypanosomes apparently
      respond to persistent ER stress by a UPR-like response, including upregulation of
      BiP, and a related spliced leader silencing (SLS) response whereby SL RNA
      transcription is shut down. Initially observed by knockdown of the secretory
      protein translocation machinery, both responses are also induced by chemical
      agents known to elicit UPR in mammalian cells (H. Goldshmidt, D. Matas, A. Kabi,
      A. Carmi, R. Hope, S. Michaeli, PLoS Pathog 6:e1000731, 2010,
      http://dx.doi.org/10.1371/journal.ppat.1000731). As these findings were generated
      primarily in procyclic-stage trypanosomes, we have investigated both responses in
      pathogenic bloodstream-stage parasites. RNA interference (RNAi) silencing of the
      core translocon subunit Trypanosoma brucei Sec61alpha (TbSec61alpha) failed to
      induce either response. Interestingly, cell growth halted within 16 h of
      silencing, but sufficient TbSec61alpha remained to allow full competence for
      translocation of nascent secretory proteins for up to 24 h, indicating that
      replication is finely coupled with the capacity to synthesize and transport
      secretory cargo. Tunicamycin and thapsigargin at concentrations compatible with
      short-term (4 h) and long-term (24 h) viability also failed to induce any of the
      indicators of UPR-like or SLS responses. Dithiothreitol (DTT) was lethal at all
      concentrations tested. These results indicate that UPR-like and SLS responses to
      persistent ER stress do not occur in bloodstream-stage trypanosomes. 

PMID- 26318398
TI  - MicroRNA-27a decreases the level and efficiency of the LDL receptor and
      contributes to the dysregulation of cholesterol homeostasis.
AB  - RATIONALE: A strong risk factor for atherosclerosis- the leading cause of heart
      attacks and strokes- is the elevation of low-density lipoprotein cholesterol (LDL
      C) in blood. The LDL receptor (LDLR) is the primary pathway for LDL-C removal
      from circulation, and their levels are increased by statins -the main treatment
      for high blood LDL-C. However, statins have low efficiency because they also
      increase PCSK9 which targets LDLR for degradation. Since microRNAs have recently
      emerged as key regulators of cholesterol homeostasis, our aim was to identify
      potential microRNA-based therapeutics to decrease blood LDL-C and prevent
      atherosclerosis. METHODS AND RESULTS: We over expressed and knocked down miR-27a
      in HepG2 cells to assess its effect on the expression of key players in the LDLR
      pathway using PCR Arrays, Elisas, and Western blots. We found that miR-27a
      decreases LDLR levels by 40% not only through a direct binding to its 3'
      untranslated region but also indirectly by inducing a 3-fold increase in PCSK9,
      which enhances LDLR degradation. Interestingly, miR-27a also directly decreases
      LRP6 and LDLRAP1, two other key players in the LDLR pathway that are required for
      efficient endocytosis of the LDLR-LDL-C complex in the liver. The inhibition of
      miR-27a using lock nucleic acids induced a 70% increase in LDLR levels and,
      therefore, it would be a more efficient treatment for hypercholesterolemia
      because of its desirable effects not only on LDLR but also on PCSK9. CONCLUSION:
      The results presented here provide evidence supporting the potential of miR-27a
      as a novel therapeutic target for the prevention of atherosclerosis.

PMID- 26318399
TI  - Association between CETP gene polymorphism, insulin resistance and risk of
      diabetes mellitus in patients with vascular disease.
AB  - INTRODUCTION: Genetic inhibition of Cholesteryl Ester Transfer Protein (CETP)
      might be associated with insulin resistance and incident type 2 diabetes mellitus
      (T2DM). This study investigated the relation between a genetic variant in the
      CETP gene and measures of insulin resistance and incident T2DM in patients with
      manifest cardiovascular disease (CVD). Furthermore the effect on risk of
      recurrent cardiovascular events was investigated. METHODS: SMART is a prospective
      cohort study performed in 5601 patients with clinically manifest CVD. We selected
      a variant (rs3764261) associated with reduced CETP activity and increased levels
      of HDL cholesterol (HDL-C). Patients were divided in three groups: 2640 wild type
      patients (GG), 2420 heterozygotes for rs3764261 (GT) and 541 homozygotes for
      rs3764261 (TT). Regression analyses were performed using an additive model.
      RESULTS: The study population consisted of 4656 patients without T2DM and 945
      patients with T2DM at baseline. Presence of rs3764261 was associated with
      increased HDL-C in patients without T2DM (beta 0.106, 95%CI 0.083-0.128) and with
      T2DM (beta 0.043, 95%CI 0.007-0.078). During a median follow up of 7.2 years (IQR
      4.7-10.2) 427 incident T2DM occurred. Presence of rs3764261 was not related to
      incident T2DM (HR 0.96, 95%CI 0.83-1.11) in patients without T2DM at baseline.
      Furthermore, presence of rs3764261 was not related to insulin resistance
      (glucose, insulin, HOMA-IR, HbA1c) or recurrent CVD (HR 0.92, 95%CI 0.84-1.02).
      CONCLUSION: Presence of CETP SNP rs3764261 is not associated with insulin
      resistance and incident T2DM in patients with clinically manifest vascular
      disease. Furthermore, no effect of rs3764261 on the risk of recurrent CVD was
      observed.

PMID- 26318400
TI  - Single-Use Energy Sources and Operating Room Time for Laparoscopic Hysterectomy:
      A Randomized Controlled Trial.
AB  - STUDY OBJECTIVES: To compare the intraoperative direct costs of a single-use
      energy device with reusable energy devices during laparoscopic hysterectomy.
      DESIGN: A randomized controlled trial (Canadian Task Force Classification I).
      SETTING: An academic hospital. PATIENTS: Forty-six women who underwent
      laparoscopic hysterectomy from March 2013 to September 2013. INTERVENTIONS: Each
      patient served as her own control. One side of the uterine attachments was
      desiccated and transected with the single-use device (Ligasure 5-mm Blunt Tip
      LF1537 with the Force Triad generator). The other side was desiccated and
      transected with reusable bipolar forceps (RoBi 5 mm), and transected with
      monopolar scissors using the same Covidien Force Triad generator. The instrument
      approach used was randomized to the attending physician who was always on the
      patient's left side. Resident physicians always operated on the patient's right
      side and used the converse instruments of the attending physician. MEASUREMENTS
      AND MAIN RESULTS: Start time was recorded at the utero-ovarian pedicle and end
      time was recorded after transection of the uterine artery on the same side. Costs
      included the single-use device; amortized costs of the generator, reusable
      instruments, and cords; cleaning and packaging of reusable instruments; and
      disposal of the single-use device. Operating room time was $94.14/min. We
      estimated that our single use-device cost $630.14 and had a total time savings of
      6.7 min per case, or 3.35 min per side, which could justify the expense of the
      device. The single-use energy device had significant median time savings (-4.7
      min per side, p < .001) and total intraoperative direct cost savings ($254.16 per
      case). CONCLUSIONS: A single-use energy device that both desiccates and cuts
      significantly reduced operating room time to justify its own cost, and it also
      reduced total intraoperative direct costs during laparoscopic hysterectomy in our
      institution. Operating room cost per minute varies between institutions and must
      be considered before generalizing our results.

PMID- 26318401
TI  - Synthesis, molecular docking, acetylcholinesterase and butyrylcholinesterase
      inhibitory potential of thiazole analogs as new inhibitors for Alzheimer disease.
AB  - A series of thirty (30) thiazole analogs were prepared, characterized by (1)H
      NMR, (13)C NMR and EI-MS and evaluated for Acetylcholinesterase and
      butyrylcholinesterase inhibitory potential. All analogs exhibited varied
      butyrylcholinesterase inhibitory activity with IC50 value ranging between 1.59+/
      0.01 and 389.25+/-1.75MUM when compared with the standard eserine (IC50, 0.85+/
      0.0001MUM). Analogs 15, 7, 12, 9, 14, 1, 30 with IC50 values 1.59+/-0.01, 1.77+/
      0.01, 6.21+/-0.01, 7.56+/-0.01, 8.46+/-0.01, 14.81+/-0.32 and 16.54+/-0.21MUM
      respectively showed excellent inhibitory potential. Seven analogs 15, 20, 19, 24,
      28, 30 and 25 exhibited good acetylcholinesterase inhibitory potential with IC50
      values 21.3+/-0.50, 35.3+/-0.64, 36.6+/-0.70, 44.81+/-0.81, 46.36+/-0.84, 48.2+/
      0.06 and 48.72+/-0.91MUM respectively. All other analogs also exhibited well to
      moderate enzyme inhibition. The binding mode of these compounds was confirmed
      through molecular docking. 

PMID- 26318403
TI  - Ambulatory laparoscopic minor hepatic surgery: Retrospective observational study.
AB  - INTRODUCTION: Over the last decade, laparoscopic hepatic surgery (LHS) has been
      increasingly performed throughout the world. Meanwhile, ambulatory surgery has
      been developed and implemented with the aims of improving patient satisfaction
      and reducing health care costs. The objective of this study was to report our
      preliminary experience with ambulatory minimally invasive LHS. METHODS: Between
      1999 and 2014, 172 patients underwent LHS at our institution, including 151 liver
      resections and 21 fenestrations of hepatic cysts. The consecutive series of
      highly selected patients who underwent ambulatory LHS were included in this
      study. RESULTS: Twenty patients underwent ambulatory LHS. Indications were liver
      cysts in 10 cases, liver angioma in 3 cases, focal nodular hyperplasia in 3
      cases, and colorectal hepatic metastasis in 4 cases. The median operative time
      was 92 minutes (range: 50-240 minutes). The median blood loss was 35 mL (range:
      20-150 mL). There were no postoperative complications or re-hospitalizations. All
      patients were hospitalized after surgery in our ambulatory surgery unit, and were
      discharged 5-7 hours after surgery. The median postoperative pain score at the
      time of discharge was 3 (visual analogue scale: 0-10; range: 0-4). The median
      quality-of-life score at the first postoperative visit was 8 (range: 6-10) and
      the median cosmetic satisfaction score was 8 (range: 7-10). CONCLUSION: This
      series shows that, in selected patients, ambulatory LHS is feasible and safe for
      minor hepatic procedures.

PMID- 26318404
TI  - Dental age estimation in Brazilian HIV children using Willems' method.
AB  - The notification of the Human Immunodeficiency Virus (HIV) in Brazilian children
      was first reported in 1984. Since that time more than 21 thousand children became
      infected. Approximately 99.6% of the children aged less than 13 years old are
      vertically infected. In this context, most of the children are abandoned after
      birth, or lose their relatives in a near future, growing with uncertain
      identification. The present study aims to estimate the dental age of Brazilian
      HIV patients in face of healthy patients paired by age and gender. The sample
      consisted of 160 panoramic radiographs of male (n: 80) and female (n: 80)
      patients aged between 4 and 15 years (mean age: 8.88 years), divided into HIV (n:
      80) and control (n: 80) groups. The sample was analyzed by three trained
      examiners, using Willems' method, 2001. Intraclass Correlation Coefficient (ICC)
      was applied to test intra- and inter-examiner agreement, and Student paired t
      test was used to determine the age association between HIV and control groups.
      Intra-examiner (ICC: from 0.993 to 0.997) and inter-examiner (ICC: from 0.991 to
      0.995) agreement tests indicated high reproducibility of the method between the
      examiners (P<0.01). Willems' method revealed discrete statistical overestimation
      in HIV (2.86 months; P=0.019) and control (1.90 months; P=0.039) groups. However,
      stratified analysis by gender indicate that overestimation were only concentrated
      in male HIV (3.85 months; P=0.001) and control (2.86 months; P=0.022) patients.
      The significant statistical differences are not clinically relevant once only few
      months of discrepancy are detected applying Willems' method in a Brazilian HIV
      sample, making this method highly recommended for dental age estimation of both
      HIV and healthy children with unknown age. 

PMID- 26318402
TI  - Family Wide Molecular Adaptations to Underground Life in African Mole-Rats
      Revealed by Phylogenomic Analysis.
AB  - During their evolutionary radiation, mammals have colonized diverse habitats.
      Arguably the subterranean niche is the most inhospitable of these, characterized
      by reduced oxygen, elevated carbon dioxide, absence of light, scarcity of food,
      and a substrate that is energetically costly to burrow through. Of all lineages
      to have transitioned to a subterranean niche, African mole-rats are one of the
      most successful. Much of their ecological success can be attributed to a diet of
      plant storage organs, which has allowed them to colonize climatically varied
      habitats across sub-Saharan Africa, and has probably contributed to the evolution
      of their diverse social systems. Yet despite their many remarkable phenotypic
      specializations, little is known about molecular adaptations underlying these
      traits. To address this, we sequenced the transcriptomes of seven mole-rat taxa,
      including three solitary species, and combined new sequences with existing
      genomic data sets. Alignments of more than 13,000 protein-coding genes
      encompassed, for the first time, all six genera and the full spectrum of
      ecological and social variation in the clade. We detected positive selection
      within the mole-rat clade and along ancestral branches in approximately 700 genes
      including loci associated with tumorigenesis, aging, morphological development,
      and sociality. By combining these results with gene ontology annotation and
      protein-protein networks, we identified several clusters of functionally related
      genes. This family wide analysis of molecular evolution in mole-rats has
      identified a suite of positively selected genes, deepening our understanding of
      the extreme phenotypic traits exhibited by this group. 

PMID- 26318405
TI  - Novel Ca2+ increases in the maturing oocytes of starfish during the germinal
      vesicle breakdown.
AB  - It has been known that the intracellular Ca(2+) level transiently rises at the
      specific stages of mitosis such as the moment of nuclear envelope breakdown and
      at the metaphase-anaphase transition. Comparable intracellular Ca(2+) increases
      may also take place during meiosis, as was intermittently reported in mouse,
      Xenopus, and starfish oocytes. In a majority of starfish species, the maturing
      oocytes display an intracellular Ca(2+) increase within few minutes after the
      addition of the maturation hormone, 1-methyladenine (1-MA). Although starfish
      oocytes at meiosis also manifest a Ca(2+) increase at the time of polar body
      extrusion, a similar Ca(2+) increase has never been observed during the envelope
      breakdown of the nucleus (germinal vesicle, GV). Here, we report, for the first
      time, the existence of an additional Ca(2+) response in the maturing oocytes of
      Asterina pectinifera at the time of GV breakdown. In contrast to the immediate
      early Ca(2+) response to 1-MA, which is independent of external Ca(2+) and takes
      a form of intracellular Ca(2+) wave traveling three times as fast as that in the
      fertilized eggs, this late stage Ca(2+) response comprised a train of numerous
      spikes representing Ca(2+) influx. These Ca(2+) spikes coinciding with GV
      breakdown were mostly eliminated when the GV was removed from the oocytes prior
      to the addition of 1-MA, suggesting that the Ca(2+) spikes are rather a
      consequence of the GV breakdown. In support of the idea that these Ca(2+) spikes
      play a physiological role, the oocytes matured in calcium-free seawater had a
      higher rate of cleavage failure 2h after the fertilization in natural seawater.
      Specific inhibitors of L-type Ca(2+) channels, verapamil and diltiazem, severely
      suppressed the amplitude of the individual Ca(2+) spikes, but not their
      frequencies. On the other hand, latrunculin-A (LAT-A), which promotes net
      depolymerization of the actin cytoskeleton, had a dual effect on this late Ca(2+)
      response. When added immediately after the hormone-dependent period, LAT-A
      inhibited the occurrence (frequency) of the spikes in a dose-dependent manner,
      but the amplitude of the prevailing Ca(2+) spikes itself was rather significantly
      increased. These results suggest that the cortical actin cytoskeleton and some
      nuclear factors may play a role in regulating ion channel activities during this
      stage of meiotic progression.

PMID- 26318406
TI  - High-Content Functional Screening of AEG-1 and AKR1C2 for the Promotion of
      Metastasis in Liver Cancer.
AB  - Liver cancer is one of the most lethal cancer types in humans, but our
      understanding of the molecular mechanisms underlying this process remains
      insufficient. Here, we conducted high-content screening of the potential genes
      involved in liver cancer metastasis, which we selected from the Kyoto
      Encyclopedia of Genes and Genomes (KEGG) pathway database, based on the SAMcell
      method and RNA interference technology. We identified two powerful genes in the
      liver cancer metastasis process, AEG-1 and AKR1C2, both of which proved to be
      positive regulators in promoting metastasis in liver cancer. Further clinical
      results verified their roles in liver cancer. In summary, these findings could
      provide new insight into the liver cancer mechanism and potentially therapeutic
      novel targets for liver cancer therapies in the future.

PMID- 26318407
TI  - Level 2 validation of a flow cytometric method for detection of Escherichia coli
      O157:H7 in raw spinach.
AB  - The Bacteriological Analytical Manual (BAM) method currently used by the United
      States Food and Drug Administration (FDA) to detect Escherichia coli O157:H7 in
      spinach was systematically compared to a new flow cytometry based method. This
      Food and Drug Administration (FDA) level 2 external laboratory validation study
      was designed to determine the latter method's sensitivity and speed for analysis
      of this pathogen in raw spinach. Detection of target cell inoculations with a low
      cell count is critical, since enterohemorrhagic strains of E. coli require an
      infective dose of as few as 10 cells (Schmid-Hempel and Frank, 2007). Although,
      according to the FDA, the infectious dose is unknown (Food and Drug
      Administration, 1993). Therefore, the inoculation level into the spinach, a total
      of 2.0+/-2.6 viable E. coli O157 cells, was specified to yield between 25% and
      75% detection by the new method, out of 20 samples (10 positives and 10
      negatives). This criterion was met in that the new method detected 60% of the
      nominally positive samples; the corresponding sensitivity of the reference method
      was 50%. For both methods the most likely explanation for false negatives was
      that no viable cells were actually introduced into the sample. In this validation
      study, the flow cytometry method was equal to the BAM in sensitivity and far
      superior in speed. 

PMID- 26318408
TI  - The effect of oxidative stress on gene expression of Shiga toxin-producing
      Escherichia coli (STEC) O157:H7 and non-O157 serotypes.
AB  - Understanding the survival mechanisms used by Shiga toxin-producing Escherichia
      coli (STEC), including O157:H7 and non-O157 serotypes, is important for
      minimizing contamination of fresh produce and occurrence of foodborne outbreaks.
      Recent outbreaks linked to leafy green vegetables and sprouted seeds have
      prompted researchers to focus on investigating decontamination strategies.
      Several studies showed that hydrogen peroxide (H2O2) treatment has been effective
      in reducing pathogens on fresh produce. As such, the effect of hydrogen peroxide
      on stress-associated and virulence gene expression in six STEC isolates was
      investigated in this study. Logarithmic phase cells of E. coli O157:H7 (EDL933)
      and non-O157 serotypes, including E. coli O26:H11 (EC20070549), O103:H2
      (EC19970811), O104:H4 (NML#11-3088), O111:NM (EC20070546) and O145:NM
      (EC19970355) were exposed to 2.5mM H2O2 for 40 min and gene expression was
      evaluated using quantitative real-time PCR. Different patterns of gene expression
      were observed in E. coli O157:H7 and non-O157 serotypes. Particularly, Shiga
      toxin gene stx2 was upregulated in O157:H7, but not in O104:H4. Moreover, stx1
      was significantly upregulated in STEC O157:H7, but only slightly upregulated Stx1
      positive non-O157 serotypes. However genes related to motility (fliC) and intimin
      gene (eae) were downregulated in most strains. Stress-associated sodA gene
      encoding manganese superoxide dismutase was significantly upregulated in all
      serotypes. The dps gene coding for non-specific DNA binding protein was
      upregulated in O145:NM, O111:NM, O103:H2 and O26:H11. However genes related to
      cold shock (cspC) and acid resistance (gadW) were significantly downregulated in
      all strains tested. The results of this study provide a basic understanding of
      the oxidative stress impact on survival and virulence of non-O157 serotype STEC
      strains.

PMID- 26318409
TI  - A novel real-time PCR assay for the specific identification and quantification of
      Weissella viridescens in blood sausages.
AB  - Weissella viridescens has been identified as one of the lactic acid bacteria
      (LAB) responsible for the spoilage of "morcilla de Burgos". In order to identify
      and quantify this bacterium in "morcilla de Burgos", a new specific PCR procedure
      has been developed. The primers and Taqman probe were designed on the basis of a
      sequence from the gene recN. To confirm the specificity of the primers, 77
      strains from the genera Carnobacterium, Enterococcus, Lactobacillus, Leuconostoc,
      Pediococcus, Streptococcus, Vagococcus and Weissella were tested by conventional
      PCR. The specificity of the primers and the correct functioning of the probe was
      confirmed by performing real-time PCR (qPCR) with 21 W. viridescens strains and
      27 strains from other LAB genera. The levels of detection and quantification for
      the qPCR procedure proposed herein were determined for a pure culture of W.
      viridescens CECT 283(T) and for "morcilla de Burgos" artificially inoculated with
      this species. The primers were specific for W. viridescens, with only one product
      of 91 bp being observed for this species. Similarly, the qPCR reactions were
      found to be specific, amplifying at a mean CT of 15.0+/-0.4 only for W.
      viridescens strains. The limit of detection (LOD) and quantification (LOQ) for
      this procedure was established in 0.082 pg for genomic DNA from W. viridescens.
      With regard to the artificially inoculated "morcilla", the limit of
      quantification was established in 80 CFU/reaction and the limit of detection in 8
      CFU/reaction. Consequently, the qPCR developed herein can be considered to be a
      good, fast, simple and accurate tool for the specific detection and
      quantification of W. viridescens in meat samples.

PMID- 26318410
TI  - Effect of alginate coatings with cinnamon bark oil and soybean oil on quality and
      microbiological safety of cantaloupe.
AB  - The quality and microbiological safety of cantaloupes can potentially be improved
      using antimicrobial coatings that are able to maintain effectiveness throughout
      storage. The objective of this work was to study the effect of coating mixtures
      containing sodium alginate and cinnamon bark oil (CBO) on the quality of
      cantaloupes and the survival of inoculated bacterial pathogens and naturally
      occurring yeasts and molds during ambient storage at 21  degrees C. Cantaloupes
      were dipped in mixtures containing 1% sodium alginate with or without 2% CBO and
      0 or 0.5% soybean oil (SBO). Weight loss and total soluble solids content of the
      flesh were not significantly different among coating treatments. However, changes
      in color and firmness of cantaloupes were delayed to different extents after
      coating, most significantly for the CBO+SBO treatment. Cocktails of Salmonella
      enterica, Escherichia coli O157:H7, or Listeria monocytogenes inoculated on
      cantaloupes were reduced to the detection limit (1.3 log CFU/cm(2)) and
      completely inhibited during the 15-day storage by the CBO+SBO treatment, while L.
      monocytogenes and S. enterica reached populations of 2.9 log CFU/cm(2) and 2.4
      log CFU/cm(2), respectively, on cantaloupes coated with CBO alone. Antimicrobial
      coatings, especially with SBO, also reduced yeast and mold counts on cantaloupes
      by 2.6 log CFU/cm(2). SBO improved the retention of CBO during storage suggesting
      it is related to the enhancement of quality and microbiological safety. Findings
      demonstrated the potential of the antimicrobial coating system studied to improve
      microbiological safety and quality of cantaloupes.

PMID- 26318412
TI  - Sculpting with people--An experiential learning technique.
AB  - At Department of Nursing, University College Lillebaelt in Denmark we use an
      experiential technique called sculpting in our simulation program. Sculpting is a
      kind of non-verbal role play in which participants are given a certain character
      and create a 'sculpture' by arranging family members, social circles and
      professionals in ways which reflect the quality of the relationships of the
      people involved. The aim of this study is to further describe the sculpting
      exercise and present a small scale evaluation study using a qualitative
      descriptive design. An evaluation sheet was formulated by the authors and filled
      out by 114 Danish third-year nursing students. The results show that sculpting is
      experienced as emotionally demanding, but in a good way. It is experienced as an
      eye-opener that helps to identify the possible complex and emotional dynamics in
      a family experiencing critical illness and impending death. Sculpting seems to
      increase nursing students' personal knowing related to palliative care. An
      experiential learning technique like sculpting can be introduced in other parts
      of nursing education to raise students' awareness of what they themselves bring
      into a situation and how this may affect their clinical judgments. 

PMID- 26318411
TI  - Psychological distress and salivary secretory immunity.
AB  - Stress-induced impairments of mucosal immunity may increase susceptibility to
      infectious diseases. The present study investigated the association of perceived
      stress, depressive symptoms, and loneliness with salivary levels of secretory
      immunoglobulin A (S-IgA), the subclasses S-IgA1, S-IgA2, and their transporter
      molecule Secretory Component (SC). S-IgA/SC, IgA1/SC and IgA2/SC ratios were
      calculated to assess the differential effects of stress on immunoglobulin
      transport versus availability. This study involved 113 university students, in
      part selected on high scores on the UCLA Loneliness Scale and/or the Beck
      Depression Inventory. Stress levels were assessed using the Perceived Stress
      Scale. Unstimulated saliva was collected and analysed for total S-IgA and its
      subclasses, as well as SC and total salivary protein. Multiple linear regression
      analyses, adjusted for gender, age, health behaviours, and concentration effects
      (total protein) revealed that higher perceived stress was associated with lower
      levels of IgA1 but not IgA2. Perceived stress, loneliness and depressive symptoms
      were all associated with lower IgA1/SC ratios. Surprisingly, higher SC levels
      were associated with loneliness and depressive symptoms, indicative of enhanced
      transport activity, which explained a lower IgA1/SC ratio (loneliness and
      depression) and IgA2/SC ratio (depression). This is the first study to
      investigate the effects of protracted psychological stress across S-IgA
      subclasses and its transporter SC. Psychological stress was negatively associated
      with secretory immunity, specifically IgA1. The lower immunoglobulin/transporter
      ratio that was associated with higher loneliness and depression suggested a
      relative immunoglobulin depletion, whereby availability was not keeping up with
      enhanced transport demand. 

PMID- 26318413
TI  - The efficacy of single-high dose inhaled corticosteroid versus oral prednisone
      treatment on exhaled leukotriene and 8-isoprostane levels in mild to moderate
      asthmatic children with asthma exacerbation.
AB  - BACKGROUND: The anti-inflammatory effect of high-dose inhaled corticosteroids
      (ICS) in children with asthma exacerbation is unknown. We aimed to investigate
      the efficacy of single-high dose ICS versus oral prednisone treatment followed by
      a course of six day high-dose ICS or oral prednisone (P) treatment on the
      concentrations of Cys-LTs and 8-isoprostane levels in the exhaled breath
      condensate (EBC) of children with asthma exacerbation. METHODS: Ninety-four
      children with moderate-severe asthma exacerbation were evaluated with asthma
      scores, peak expiratory flow rate (PEF), forced expiratory volume in first second
      (FEV1) and exhaled Cys-LT and 8-isoprostane levels before and after treatment.
      EBC was collected from 52 patients before and four hours after treatment with
      inhaled fluticasone propionate (FP) (4000 MUg) or P and after six days of
      treatment with FP-1000 MUg/day or P. Cys-LTs and 8-isoprostane concentrations
      were determined using a specific immunoassay kit. RESULTS: Both single high-dose
      FP (n=59) and p (n=35) treatment resulted in a significant improvement in asthma
      score (p<0.0001), PEF (p<0.0001), and FEV1 (p<0.0001). Cys-LT concentration in
      the EBC decreased significantly both after the initial treatment (p=0.001), and
      at the end of the six-day period in the FP group (p<0.0001). 8-Isoprostane
      concentration was lower only after six days of treatment with FP-1000 MUg/day in
      the FP group (p=0.023). There was a significant decrease in exhaled Cys-LTs after
      four hours (p=0.012) and six days of P treatment (p=0.018) in children with
      asthma exacerbation. CONCLUSIONS: High-dose ICS treatment may be useful in the
      treatment of children with asthma exacerbation. The effects start as early as
      after four hours. The suppression of Cys-LTs production contributes to the early
      effects. Suppression of both Cys-LTs and oxidants may favourably contribute to
      the effects observed later.

PMID- 26318414
TI  - Risk factors for recurrent wheezing--International Study of Wheezing in Infants
      (EISL) phase 3.
AB  - BACKGROUND: We aimed to identify factors associated with recurrent wheezing (RW)
      in infants in the first year of life living in the Southern region of Sao Paulo
      city and participating in the "Estudio Internacional de Sibilancias en Lactantes
      (EISL)" - phase 3 (P3). METHODS: 1335 parents of infants who were attended in
      primary care health units in the Southern region of Sao Paulo city from 2009 to
      2010 answered the EISL-P3 written questionnaire. The wheezing group was
      stratified in accordance to the frequency of wheezing episodes as occasional
      wheezing (OW, less than three episodes), or RW (three or more episodes). Wheezing
      associated factors were evaluated using multivariate analysis and were expressed
      as odds ratio (OR) and 95% confidence interval (95%CI). RESULTS: The most
      relevant factors related to OW were pneumonia (OR=3.10, 95%CI=1.68-5.73),
      hospitalisation due to pneumonia (OR=2.88, 95%CI=1.26-6.56) and recurrent upper
      respiratory infection (URI, OR=1.87, 95%CI=1.25-2.81). Regarding RW, recurrent
      URI (OR=5.34, 95%CI=3.83-7.45), pneumonia (OR=4.06, 95%CI=2.87-5.74) and
      asthmatic siblings (OR=3.02, 95%CI=1.67-5.45) were the most significantly
      associated factors. CONCLUSIONS: In the present study, we found that recurrent
      URI, positive history of pneumonia and familiar history of asthma were the most
      relevant factors associated with RW. The precocious knowledge of these factors
      can enable the identification of the probable asthmatic infants and can improve
      both prevention strategies and treatment of these patients.

PMID- 26318415
TI  - The plasma gelsolin levels in atopic dermatitis: Effect of atopy and disease
      severity.
AB  - BACKGROUND: Gelsolin is an actin-binding protein with several cellular functions
      including anti-apoptosis and is reported to have an anti-inflammatory effect.
      Apoptosis of keratinocytes has been implicated as a key mechanism of atopic
      dermatitis (AD). OBJECTIVE: We aimed to determine plasma gelsolin (pGSN) levels
      in children with atopic dermatitis (AD). METHOD: The diagnosis of AD was made
      according to Hanifin and Rajka criteria. The disease severity was scored by
      objective SCORAD index by the same allergist. Skin prick testing (SPT), total IgE
      levels, and eosinophil counts were analyzed. The pGSN levels were determined
      using ELISA technique. RESULTS: Children aged between 0.5 and 3.0 years were
      included in the study. The children with AD (AD; n=84) were analyzed in two
      groups according to the presence (AD+/Atopy+; n=54) or absence of SPT positivity
      (AD+/Atopy-; n=30). The comparisons were made with a healthy control group
      matched for age and sex (n=81). The median (interquartile range) of pGSN levels
      in AD+/A+, AD+/A- and control groups were 267MUg/ml (236-368), 293 (240-498) and
      547 (361-695), respectively (p<0.001). The difference between the control group
      and AD sub-groups remained significant after Bonferroni correction (p<0.001).
      Correlation analysis failed to reach significance with the disease severity total
      IgE levels and eosinophil counts. CONCLUSION: This is the first study
      investigating the association of pGSN levels with AD and disease severity. pGSN
      levels decreased in AD. These findings suggest that gelsolin may have a role in
      the disease process in AD patients.

PMID- 26318417
TI  - The business traveler. A new high-risk traveler profile?

PMID- 26318416
TI  - Farnesol, a sesquiterpene alcohol in essential oils, ameliorates serum allergic
      antibody titres and lipid profiles in ovalbumin-challenged mice.
AB  - BACKGROUND: Farnesol, a natural sesquiterpene alcohol in essential oils, was
      found to have potential for alleviating massive inflammation, oxidative stress
      and lung injury. However, effects of farnesol supplementation on allergic asthma
      remain unclear. OBJECTIVES: To clarify the puzzle, this work investigates the
      effects of farnesol on allergic asthma using an ovalbumin (OVA)-sensitised and
      challenged mouse model. METHODS: Farnesol was administered to OVA-sensitised and
      challenged mice for 5 weeks. Three farnesol doses, namely 5, 25 and 100mg
      farnesol/kg BW/day, non-sensitised control, dietary control, and positive control
      (dexamethasone 3mg/kg BW by gavage) were included. Sera and bronchoalveolar
      lavage fluids from the experimental mice were collected to measure farnesol
      concentrations, serum lipid profiles, antibody titres, differential cell counts
      or Th1/Th2 cytokines levels. RESULTS: The results showed that farnesol
      supplementation increased serum farnesol concentration dose-dependently,
      significantly increased (P<0.05) OVA-specific IgG2a/IgE antibody titre ratios,
      but decreased total IgE levels. Farnesol supplementation markedly reversed the
      aberrated LDL-c/HDL-c and HDL-c/TC ratios in the sera of asthmatic mice,
      suggesting that farnesol supplementation might ameliorate serum lipid profiles in
      the OVA-sensitised and challenged mice. CONCLUSION: Our results evidenced that
      farnesol supplementation might improve serum allergic antibody titres and lipid
      profiles in asthmatic mice.

PMID- 26318418
TI  - Epibrassinolide alters PI3K/MAPK signaling axis via activating Foxo3a-induced
      mitochondria-mediated apoptosis in colon cancer cells.
AB  - Epibrassinolide (EBR), a steroid-derived plant growth regulator, has been
      recently suggested as an apoptotic inducer in different cancer cells. In this
      experimental study, we investigated the potential apoptotic effect of EBR on
      stress-related and survival signaling molecules in colon carcinoma cells. EBR
      decreased cell viability and colony formation in HCT 116 and HT-29 colon
      carcinoma cells. The inactivation of PI3K/AKT by EBR treatment led to
      upregulation of Foxo3a, which in turn induced apoptosis in HCT 116 and HT-29
      cells. In addition, the upstream non-receptor protein tyrosine kinase Src was
      found elevated allowing to the upregulation of p38, stress-activated protein
      kinase/Jun amino-terminal kinase and extracellular signal-regulated kinase 1/2
      and their target genes c-jun, c-fos and c-myc in a time-dependent manner in HCT
      116 cells within 48h. The alterations in PA metabolism caused intracellular PA
      pool decrease. The upregulation of pro-apoptotic Bak, Bax, Puma and Bim were
      accompanied with the decrease in Mcl-1 in HCT 116 and Bcl-xL expression profiles
      in HT-29 following 48h EBR treatment. We suggest that the upregulation of Bim
      expression levels might be related with one of the PI3K/AKT target transcription
      factor Foxo3a, which was dephosphorylated by EBR treatment in HCT 116 and HT-29
      cells.